PMID- 18316981
TI  - A fatal tick bite occurring during the course of tick-borne encephalitis
      vaccination.
AB  - In Western Europe tick-borne encephalitis virus infections with fatal outcome are
      rare, especially in children. We report the case of an adolescent who died of
      meningoencephalitis after a tick bite that occurred between the first 2 tick
      borne encephalitis vaccinations. The case demonstrates the difficulty of
      differentiating possible adverse events associated with the immunization from
      symptoms of simultaneous infection with tick-borne encephalitis virus.

PMID- 18316982
TI  - Detection of astrovirus in premature infants with necrotizing enterocolitis.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a major cause of mortality and
      morbidity in very low birth weight infants (<1500 g birth weight). Although the
      etiology remains unknown, infectious agents could play a key role. The aim of
      this analysis was to examine the role of human astrovirus (HAstV) in infants with
      NEC. PATIENTS AND METHODS: All patients admitted during a 5-year period at a
      tertiary neonatal intensive care unit with NEC (Bell stage I-III) who had
      examination of stool specimens for bacterial and for viral infections were
      included. Clinical data were reviewed and compared between infants with NEC and
      astrovirus detection (NEC + HAstV) and infants with NEC without astrovirus
      detection (NEC - HAstV) in stool specimens. RESULTS: Forty infants with NEC were
      identified between 2002 and 2006 and 8 patients were excluded from statistical
      evaluation because of incomplete viral examinations. HAstV was detected in stool
      specimens of 6 (19%) of the remaining 32 patients with NEC. Double infection with
      rotavirus was identified in 1 patient. No other viruses were detected.
      Significant differences in patients with NEC - HAstV and NEC + HAstV were only
      shown for age at onset of illness (P < 0.001) but not for severity of illness,
      need for surgical intervention, or mortality. CONCLUSIONS: This study
      demonstrates that HAstV may be associated with the development of NEC in a
      subgroup of patients and provides further evidence for the important role of
      gastrointestinal viral infections in this most common gastrointestinal emergency
      in premature infants. HAstV should be included in microbiological examination of
      stool specimens in patients with NEC.

PMID- 18316983
TI  - Prevalence of ceftriaxone-induced red blood cell antibodies in pediatric patients
      with sickle cell disease and human immunodeficiency virus infection.
AB  - Ceftriaxone can be associated with catastrophic immune hemolysis in pediatric
      patients, particularly those with underlying diseases such as sickle cell disease
      and human immunodeficiency virus infection. We designed a study to screen for
      ceftriaxone-induced RBC antibodies in these 2 pediatric populations. The
      prevalence of anticeftriaxone antibody was 12.5% (8 of 64). Two of these 8
      patients with the antibody experienced hemolysis; 1 case was fatal.

PMID- 18316984
TI  - Human bocavirus detection in nasopharyngeal aspirates of children without
      clinical symptoms of respiratory infection.
AB  - The main objective of our study was to determine the frequency of human bocavirus
      (HBoV) detection in asymptomatic children and to compare it with that in children
      hospitalized because of respiratory infection. HBoV was detected in 5% of 116
      healthy children versus 17% of 908 hospitalized children. HBoV can be detected in
      healthy children but with a significantly lower frequency than in ill children.

PMID- 18316985
TI  - Diphtheria-tetanus-acellular pertussis and inactivated poliovirus vaccines given
      separately or combined for booster dosing at 4-6 years of age.
AB  - BACKGROUND: In the United States, diphtheria-tetanus-acellular pertussis (DTaP)
      and inactivated poliovirus (IPV) booster vaccinations are recommended for
      children 4-6 years of age. A combined DTaP-IPV vaccine is being developed, which
      would reduce by one the number of injections in this age group. METHODS: Children
      4-6 years of age were randomized (1:1:1:1) to receive booster vaccination with 1
      of 3 combined DTaP-IPV lots plus the measles, mumps, and rubella vaccine (N =
      3156 for pooled lots) or separate doses of DTaP + IPV + measles, mumps, and
      rubella vaccine (N = 1053). Immunogenicity was assessed in a subset of children
      (N = 1331). Safety (solicited and unsolicited symptoms) including detailed
      assessment of local swelling reactions, was assessed in all children. RESULTS:
      Increases in antibody geometric mean concentrations/titers 1 month after
      vaccination were observed for the diphtheria, tetanus, acellular pertussis, and
      polio antigens. At least 92.2% of combined DTaP-IPV subjects and 92.6% of
      separate DTaP + IPV subjects had a postvaccination booster response for one or
      more DTaP antigens. Booster responses to one or more poliovirus antigens were
      observed in at least 96.6% of combined DTaP-IPV subjects and 92.8% of separate
      DTaP + IPV subjects. The combined DTaP-IPV vaccine was noninferior to separately
      administered DTaP and IPV vaccines with respect to DTaP antigen booster response
      rates and poliovirus antibody geometric mean titers ratios. Reporting of
      solicited local and systemic events was comparable between both groups.
      CONCLUSIONS: The combination DTaP-IPV vaccine provided immunogenicity and
      reactogenicity that is comparable to separately administered DTaP and IPV
      vaccines, with the advantage of requiring one less injection.

PMID- 18316986
TI  - Impact of conjugate vaccine on transmission of antimicrobial-resistant
      Streptococcus pneumoniae among Alaskan children.
AB  - BACKGROUND: The impact of heptavalent pneumococcal conjugate vaccine (PCV7) on
      transmission of antimicrobial-resistant Streptococcus pneumoniae is an important
      concern for countries considering PCV7 introduction. METHODS: Every winter from
      2000 to 2004, as PCV7 was routinely introduced, we obtained nasopharyngeal swabs
      for pneumococcal culture, serotyping, and susceptibility testing from 150
      children aged 3-59 months at each of 3 Anchorage, Alaska clinics. We assessed
      risk factors for pneumococcal carriage, including vaccination status and
      antimicrobial use. RESULTS: Between 2000 and 2004, 2250 nasopharyngeal swabs from
      2061 infants and children were collected. The proportion of children receiving >
      or = 1 PCV7 vaccination increased from 0 to 89%, whereas overall pneumococcal
      carriage remained stable (38% versus 41%, respectively). Among S. pneumoniae
      carriers, we observed declines in carriage of PCV7 serotypes (from 54% to 10%, P
      < 0.01) and trimethoprim-sulfamethoxazole nonsusceptible strains (44% to 16%, P <
      0.01), but not in PCN-nonsusceptible strains (36% versus 37%). Among PCN
      nonsusceptible types, the proportion of serotype 19A strains increased from 10%
      to 32% (P = 0.0002). Recent beta-lactam use was stable throughout the period (29%
      overall), whereas trimethoprim-sulfamethoxazole use declined from 6% to 2% (P =
      0.02). CONCLUSIONS: PCV7 vaccination in the first 5 years did not affect overall
      pneumococcal carriage, but was associated with a shift in serotype distribution
      from PCV7 types to non-PCV7 types. With persistent pressure of some
      antimicrobials, reductions in carriage of antimicrobial nonsusceptible PCV7 types
      may be offset by increases in carriage of nonsusceptible non-PCV7 types.

PMID- 18316987
TI  - Varicella zoster virus associated acute aseptic meningitis without exanthem in an
      immunocompetent 14-year-old boy.
AB  - Neurologic complications can occur with varicella-zoster virus (VZV) infection,
      usually after vesicular exanthem. We report the case of a previously healthy 14
      year-old boy with aseptic meningitis as a result of reactivated-VZV infection
      without exanthem. Diagnosis was made by detection of VZV-DNA in cerebrospinal
      fluid. VZV should be considered in cases of aseptic meningitis, even without a
      history of exanthem or immune compromise.

PMID- 18316988
TI  - Single-dose pharmacokinetics of daptomycin in children with suspected or proved
      gram-positive infections.
AB  - BACKGROUND: New antimicrobials such as daptomycin fill a void in the growing need
      for antibiotics effective against resistant Gram-positive pathogens. Although the
      pharmacokinetics of daptomycin have been well characterized in adults, no studies
      have evaluated the pharmacokinetics and tolerability in a pediatric population.
      METHODS: Twenty-five children (12-17 years, n = 8; 7-11 years, n = 8; 2-6 years,
      n = 9) were enrolled in this multicenter, open-label study. Daptomycin was
      administered as a single 4-mg/kg intravenous dose followed by repeated blood
      sampling for 24 hours. Daptomycin was quantitated from plasma using a validated
      high performance liquid chromatography method and pharmacokinetic variables
      determined using a model-dependent approach. RESULTS: Daptomycin systemic
      exposure decreased with decreasing age, reflecting more rapid rates of clearance
      in younger children. Total body exposure estimates in adolescents were
      approximately 1.7x those observed in children <6 years of age (374.4 versus 215.3
      microg*h/L), they were comparable to those observed in adult historic controls.
      Estimates of apparent elimination half-life averaged 6.7 hours in adolescents,
      5.6 hours in children 7-11 years of age, and 5.3 hours in children <6 years of
      age. One child had an adverse event (infusion site reaction) considered to be
      related to study drug. CONCLUSIONS: Systemic drug exposure after a single weight
      adjusted daptomycin dose is reduced in younger children compared with adolescents
      and adults consequent to an apparent age-associated change in total plasma
      clearance.

PMID- 18316989
TI  - Tympanometric findings in young children during upper respiratory tract
      infections with and without acute otitis media.
AB  - BACKGROUND: Upper respiratory tract infections (URI) likely lead to acute otitis
      media (AOM) by causing Eustachian tube dysfunction which creates negative middle
      ear pressure. Children younger than 2 years of age are at highest risk for AOM
      compared with older children and adults. There has been no published study
      comparing the middle ear status during URI in infants and young children by age
      group. METHODS: We analyzed data from a prospective, longitudinal study of virus
      induced AOM. Healthy children 6-35 months of age were enrolled in a study
      designed to capture all AOM after URI during a 1-year follow-up period.
      Tympanometry was used to address the middle ear status; tympanometric findings
      during the first week of URI were compared among different age groups.
      Tympanograms were classified into type A (normal), type B (middle ear effusion),
      and type C (negative middle ear pressure). RESULTS: Children 6-11 months of age
      with URI experienced abnormal tympanograms more frequently than older children (P
      < 0.001). The peak day for an abnormal tympanogram was day 2 of the URI. Abnormal
      tympanogram tended to be type B in children age 6-23 months and type C in
      children age 24-47 months (P < 0.001). One-third of children older than 24 months
      of age had type C tympanogram during the first week of URI. CONCLUSIONS:
      Eustachian tube dysfunction and middle ear abnormality during URI are more severe
      in children younger than 2 years of age, compared with older children. These
      findings could help explain the higher incidence of AOM after URI in younger
      children.

PMID- 18316990
TI  - Impact of empiric antibiotic use on development of infections caused by extended
      spectrum beta-lactamase bacteria in a neonatal intensive care unit.
AB  - BACKGROUND: The neonatal intensive care unit at Miller Children's Hospital
      changed from empiric use of cefotaxime and vancomycin (CEF) to tobramycin and
      vancomycin (TOB) for hospital-acquired infections in November 1999 because of an
      increase in infections caused by extended-spectrum beta-lactamase (ESBL)
      producing bacteria. The objectives of this study were to evaluate the incidence
      and impact of this change on the development of ESBL infections. METHODS: We
      retrospectively reviewed medical records of infants who received CEF or TOB
      between January 1998 and December 2002. A standardized form was used to collect
      demographic data, information on antibiotic use, and culture results. RESULTS:
      The mean gestational age and birth weight of the 250 infants were 28.8 +/- 4.0
      weeks and 1213.1 +/- 662 g, respectively. There were no differences between
      infants who received CEF (N = 130) or TOB (N = 120) in terms of gestational age,
      birth weight, device use, invasive procedures, or prior antibiotic use. There
      were 11 ESBL infections. Infants in the CEF group were more likely than those in
      the TOB group to develop ESBL infection (7.8% versus 0.8%, P = 0.008). There were
      11 deaths, with none attributed to ESBL infection. In a multivariate analysis,
      duration of prior ampicillin and gentamicin use and exposure to CEF were
      associated with ESBL infection [odds ratio (OR): 3.1, 95% confidence interval
      (CI): 1.28-7.49, P = 0.012; and OR: 33.7; 95% CI: 1.02-1136, P = 0.05,
      respectively]. CONCLUSIONS: The change from empiric use of CEF to TOB was
      associated with a significant decrease in the incidence of ESBL infections.

PMID- 18316991
TI  - Chronic norovirus and adenovirus infection in a solid organ transplant recipient.
AB  - A 10-month-old boy developed chronic diarrhea 2 months after a combined liver,
      pancreas, and small bowel transplant. Norovirus and adenovirus were detected in
      multiple stool specimens during a 114-day period. Enteric viral infectious should
      be considered in solid organ transplant recipients with chronic diarrhea.

PMID- 18316992
TI  - Test characteristics and interpretation of cerebrospinal fluid gram stain in
      children.
AB  - BACKGROUND: Few data exist regarding the test characteristics of cerebrospinal
      fluid (CSF) Gram stain among children at risk for bacterial meningitis,
      especially the rate of false positive Gram stain. METHODS: We conducted a
      retrospective cohort study of children seen in the emergency department of
      Children's Hospital Boston who had CSF obtained between December 1992 and
      September 2005. Patients who had ventricular shunts, as well as those who
      received antibiotics before CSF was obtained were excluded. Test characteristics
      of CSF Gram stain were assessed using CSF culture as the criterion standard.
      Patients were considered to have bacterial meningitis if there was either: (1)
      growth of a pathogen, or (2) growth of a possible pathogen noted on the final CSF
      culture report and the patient was treated with a course of parenteral
      antibiotics for 7 days or more without other indication. RESULTS: A total of
      17,569 eligible CSF specimens were collected among 16,036 patients during the 13
      year study period. The median age of study subjects was 74 days. Seventy CSF
      specimens (0.4%) had organisms detected on Gram stain. The overall sensitivity of
      Gram stain to detect bacterial meningitis was 67% [42 of 63; 95% confidence
      interval (CI): 54-78] with a positive predictive value of 60% (42 of 70; 95% CI:
      48-71). Most patients without bacterial meningitis have negative Gram stain
      [specificity 99.9% (17,478 of 17,506; 95% CI: 99.8-99.9)] with a negative
      predictive value of 99.9 (17,478 of 17,499; 95% CI: 99.8-99.9). CONCLUSIONS: CSF
      Gram stain is appropriately used by physicians in risk stratification for the
      diagnosis and empiric treatment of bacterial meningitis in children. Although a
      positive Gram stain result greatly increases the likelihood of bacterial
      meningitis; the result may be because of contamination or misinterpretation in
      40% of cases and should not, by itself, result in a full treatment course for
      bacterial meningitis.

PMID- 18316993
TI  - Universal hepatitis A vaccination in the United States: a call for action.
AB  - Previous hepatitis A recommendations for the United States targeted vaccination
      of at-risk individuals and children living in states and communities with
      consistently elevated rates of hepatitis A. Recommendations now call for routine
      hepatitis A vaccination of all children in the United States beginning at age 1
      year (12-23 months). Currently, vaccination coverage rates for hepatitis A remain
      below rates of other routine childhood vaccines. Achieving a national
      immunization rate greater than 90% for the recommended 2 doses of hepatitis A
      vaccine would lessen disease impact throughout society. Routine childhood
      immunization against hepatitis A can be a highly effective strategy to reduce
      infection in children and community transmission of the virus, and the
      elimination of indigenous transmission of hepatitis A is an attainable goal.

PMID- 18316994
TI  - Prevalence of urinary tract infection in childhood: a meta-analysis.
AB  - BACKGROUND: Knowledge of baseline risk of urinary tract infection can help
      clinicians make informed diagnostic and therapeutic decisions. We conducted a
      meta-analysis to determine the pooled prevalence of urinary tract infection (UTI)
      in children by age, gender, race, and circumcision status. METHODS: MEDLINE and
      EMBASE databases were searched for articles about pediatric urinary tract
      infection. Search terms included urinary tract infection, cystitis,
      pyelonephritis, prevalence and incidence. We included articles in our review if
      they contained data on the prevalence of UTI in children 0-19 years of age
      presenting with symptoms of UTI. Of the 51 articles with data on UTI prevalence,
      18 met all inclusion criteria. Two evaluators independently reviewed, rated, and
      abstracted data from each article. RESULTS: Among infants presenting with fever,
      the overall prevalence (and 95% confidence interval) of UTI was 7.0% (CI: 5.5
      8.4). The pooled prevalence rates of febrile UTIs in females aged 0-3 months, 3-6
      months, 6-12 months, and >12 months was 7.5%, 5.7%, 8.3%, and 2.1% respectively.
      Among febrile male infants less than 3 months of age, 2.4% (CI: 1.4-3.5) of
      circumcised males and 20.1% (CI: 16.8-23.4) of uncircumcised males had a UTI. For
      the 4 studies that reported UTI prevalence by race, UTI rates were higher among
      white infants 8.0% (CI: 5.1-11.0) than among black infants 4.7% (CI: 2.1-7.3).
      Among older children (<19 years) with urinary symptoms, the pooled prevalence of
      UTI (both febrile and afebrile) was 7.8% (CI: 6.6-8.9). CONCLUSIONS: Prevalence
      rates of UTI varied by age, gender, race, and circumcision status. Uncircumcised
      male infants less than 3 months of age and females less than 12 months of age had
      the highest baseline prevalence of UTI. Prevalence estimates can help clinicians
      make informed decisions regarding diagnostic testing in children presenting with
      signs and symptoms of urinary tract infection.

PMID- 18316995
TI  - Inpatient mortality in children with clinically diagnosed malaria as compared
      with microscopically confirmed malaria.
AB  - BACKGROUND: Inpatient treatment for malaria without microscopic confirmation of
      the diagnosis occurs commonly in sub-Saharan Africa. Differences in mortality in
      children who are tested by microscopy for Plasmodium falciparum infection as
      compared with those not tested are not well characterized. METHODS: A
      retrospective chart review was conducted of all children up to 15 years of age
      admitted to Mulago Hospital, Kampala, Uganda from January 2002 to July 2005, with
      a diagnosis of malaria and analyzed according to microscopy testing for P.
      falciparum. RESULTS: A total of 23,342 children were treated for malaria during
      the study period, 991 (4.2%) of whom died. Severe malarial anemia in 7827 (33.5%)
      and cerebral malaria in 1912 (8.2%) were the 2 common causes of malaria-related
      admissions. Children who did not receive microscopy testing had a higher case
      fatality rate than those with a positive blood smear (7.5% versus 3.2%, P <
      0.001). After adjustment for age, malaria complications, and comorbid conditions,
      children who did not have microscopy performed or had a negative blood smear had
      a higher risk of death than those with a positive blood smear [odds ratio (OR):
      3.49, 95% confidence interval (CI): 2.88-4.22, P < 0.001; and OR: 1.59, 95% CI:
      1.29-1.96, P < 0.001, respectively]. CONCLUSIONS: Diagnosis of malaria in the
      absence of microscopic confirmation is associated with significantly increased
      mortality in hospitalized Ugandan children. Inpatient diagnosis of malaria should
      be supported by microscopic or rapid diagnostic test confirmation.

PMID- 18316996
TI  - Nevirapine, stavudine and lamivudine pharmacokinetics in African children on
      paediatric fixed-dose combination tablets.
AB  - OBJECTIVE: Triomune Baby and Junior have been developed in response to the urgent
      need for appropriate paediatric fixed-dose combination antiretroviral tablets,
      with higher nevirapine to stavudine and lamivudine ratios than adult tablets, in
      accordance with paediatric recommendations. We determined whether this ratio
      results in optimal exposure in the target population. METHODS: Seventy-one
      Zambian children were treated with Triomune Baby or Junior dosed according to
      weight bands. After 4 weeks or more, a 12-h pharmacokinetic curve was recorded.
      Antiretroviral plasma concentrations were assayed by high-performance liquid
      chromatography. RESULTS: Six children were excluded because of poor adherence. Of
      the remaining 65, 24 (37%) were female, 24 (37%) weighed less than 15 kg and most
      were malnourished. Mean (range) nevirapine C12h, Cmax and AUC12h of 6.0 (1.4,
      16.9) mg/l, 10.0 (3.8, 22.5) mg/l and 94.4 (32.1, 232) mg/l per hour were higher
      than those reported in adults. Nevirapine C12h was subtherapeutic (< 3.0 mg/l) in
      four children (6%). Mean stavudine and lamivudine C12h, Cmax, AUC12h (< 0.015
      mg/l, 0.45 mg/l, 1.05 mg/l per hour and 0.09 mg/l, 1.33 mg/l, 5.42 mg/l per hour)
      were comparable to adults. There was no evidence of a difference in nevirapine
      AUC12h across weight bands (P = 0.2), whereas the difference in stavudine (P =
      0.0003) and lamivudine AUC12h (P = 0.01) was driven by the single weight band
      with unequal dosing. CONCLUSION: Nevirapine concentrations were higher but more
      variable than in adults; the pharmacokinetic parameters of stavudine and
      lamivudine were comparable to adults. As nevirapine underdosing is of greater
      concern than overdosing, the Triomune Baby and Junior ratio appears to be
      appropriate for children weighing 6 kg and over. Further research is required for
      children under 6 kg.

PMID- 18316997
TI  - Male circumcision for HIV prevention: from evidence to action?

PMID- 18316998
TI  - Differential gene expression indicates that 'buffalo hump' is a distinct adipose
      tissue disturbance in HIV-1-associated lipodystrophy.
AB  - OBJECTIVE: To elucidate the molecular basis of the progressive enlargement of
      dorso-cervical adipose tissue, the so-called 'buffalo hump', that appears in a
      sub-set of patients with HIV-1/HAART-associated lipodystrophy. DESIGN: Analysis
      of the expression of marker genes of mitochondrial function, adipogenesis,
      inflammation and cell proliferation in ten 'buffalo hump' samples and ten
      subcutaneous fat samples from HIV-1-infected/HAART-treated patients, and in ten
      healthy controls. METHODS: Quantitative real-time polymerase chain reaction
      analysis of mitochondrial DNA and gene transcripts, and immunoblot for specific
      proteins. RESULTS: 'Buffalo hump' patients had lower levels of mitochondrial DNA
      and mitochondrial DNA-encoded transcripts with respect to healthy controls. The
      uncoupling protein (UCP)-1 gene was expressed only in 'buffalo hump' fat. There
      were no significant changes in the expression of UCP2, UCP3 or of marker genes of
      adipogenesis in 'buffalo hump' patients relative to healthy controls. 'Buffalo
      hump' fat did not show the high expression of tumor necrosis factor-alpha and
      beta2-microglobulin identified in lipoatrophic subcutaneous fat from patients.
      The expression of the macrophage marker CD68 was also lower in 'buffalo hump'
      than in subcutaneous fat from patients. In contrast, 'buffalo hump' showed a
      higher expression of the cell proliferation marker PCNA. CONCLUSIONS: 'Buffalo
      hump' adipose tissue shows specific disturbances in gene expression with respect
      to subcutaneous fat from HIV-1-infected/HAART-treated patients. Mitochondrial
      alterations cannot explain the differential behavior of 'buffalo hump' with
      respect to adipose depots prone to lipoatrophy. The absence of a local
      inflammatory status in 'buffalo hump' may explain in part the differential
      behavior of this adipose tissue.

PMID- 18316999
TI  - Antigenic stimulation in the simian model of HIV infection yields dilated
      cardiomyopathy through effects of TNFalpha.
AB  - OBJECTIVE: To investigate a role for endogenous myocardial cytokine production in
      the development of HIV-associated cardiomyopathy. DESIGN: Cardiomyopathy is a
      late-stage sequela of HIV infection. Although pathogenesis of this condition in
      HIV infection is poorly defined, inflammatory cytokines are recognized for their
      detrimental effects on myocardial structure and function. HIV infection is
      characterized by chronic immune activation and inflammatory cytokine
      dysregulation. As the myocardium itself is a rich potential source of
      inflammatory cytokines, HIV-mediated cytokine dysregulation may be an important
      contributor to development of HIV cardiomyopathy. An antigenic stimulation
      protocol conducted in the simian immunodeficiency virus (SIV) model of HIV
      infection was used to study the effects of endogenous cytokine production on
      myocardial structure and function. METHODS: Twenty-six rhesus monkeys were
      assigned to treatment groups for a 35-day study. Animals were SIV-infected; SIV
      infected and treated with killed Mycobacterium avium complex bacteria (MAC); SIV
      infected, MAC-treated, and given the TNFalpha antagonist etanercept; or
      uninfected and MAC-treated. All animals were subjected to weekly
      echocardiographic studies. Hearts were collected for further evaluation at
      euthanasia. RESULTS: SIV-infected, MAC-treated animals developed significant
      systolic dysfunction [left ventricular ejection fraction (LVEF) decline of 19 +/-
      2%] and ventricular chamber dilatation [left ventricular end-diastolic diameter
      (LVEDD) increase of 26 +/- 6%] not seen in other groups. Concurrent treatment
      with etanercept prevented development of these changes, implicating a causative
      role of myocardial TNFalpha. CONCLUSIONS: SIV-infected animals develop
      exaggerated myocardial pathology on stimulation with the ubiquitous environmental
      agent MAC. These responses are TNFalpha-dependent and may play a significant role
      in the development of cardiomyopathy in HIV infection.

PMID- 18317000
TI  - Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected
      individuals.
AB  - OBJECTIVES: Natural killer (NK) cell activity is increased in individuals who
      remain uninfected despite repeated exposures to HIV. Given that a combined major
      histocompatibility complex (MHC) class I and killer immunoglobulin-like receptor
      (KIR) KIR3D genotype has been linked to rate of HIV disease progression, we
      assessed whether these genotypes played a role in protection from infection.
      DESIGN: The study genotyped 80 HIV-exposed uninfected (EU) and 304 subjects in
      HIV primary infection (PI) at the MHC class IB and KIR3DS/L1 loci. METHODS: KIR3D
      genotyping was performed by sequence-specific primer polymerase chain reaction
      using two pairs of specific primers for each locus. The MHC class IB locus was
      typed by sequence-specific oligonucleotide polymerase chain reaction and
      sequencing to resolve Bw4 and Bw6 alleles and the amino acid present at position
      80. RESULTS: Comparison of the genetic distribution of KIR3D, HLA Bw4 and HLA Bw4
      I80 genotypes in EU versus PI subjects reveal an increased proportion of KIR3DS1
      homozygotes in EU (11/80, 13.8%) compared to subjects in PI (16/304, 5.3%).
      Analyses of combined MHC class I and KIR3D expression show no differences between
      the two populations. CONCLUSIONS: Homozygosity for the activating NK receptor
      KIR3DS1, may contribute to the more active NK cell function observed in EU and
      their relative resistance to HIV infection.

PMID- 18317001
TI  - Incidence and risk factors for the immune reconstitution inflammatory syndrome in
      HIV patients in South Africa: a prospective study.
AB  - OBJECTIVE: To determine the incidence, clinical manifestations, risk factors and
      outcome of immune reconstitution inflammatory syndrome (IRIS) in South Africa.
      DESIGN: Prospective surveillance cohort and nested case-control study in a large,
      University hospital-based antiretroviral therapy (ART) clinic. METHODS: A total
      of 423 ART-naive HIV-infected South African patients were followed for signs and
      symptoms IRIS during the first 6 months of ART. We also performed a nested case
      control study with controls matched to IRIS cases on ART duration. RESULTS:
      During the first 6 months of ART, 44 (10.4%) patients experienced IRIS for an
      overall incidence rate of 25.1 cases per 100 patient-years. Diagnoses included
      tuberculosis (18/44, 41%), abscess formation and suppurative folliculitis (8/44,
      18.2%), varicella zoster (6/44, 13.6%), herpes simplex (4/44, 9.1%), cryptococcal
      meningitis (3/44, 6.8%), molluscum contagiosum (3/44, 6.8%), and Kaposi's sarcoma
      (2/44, 4.5%). Median IRIS onset was 48 days (interquartile range, 29-99) from ART
      initiation. In comparison with controls, IRIS cases had significantly lower CD4
      cell counts at baseline (79 versus 142 cells/microl; P = 0.02) and at IRIS
      diagnosis (183 versus 263 cells/microl; P = 0.05), but similar virological and
      immunological response to ART. In multivariable analyses, higher baseline CD4
      cell count was protective of developing IRIS (HR 0.72 per 50 cells/microl
      increase). Most IRIS cases were mild, with ART discontinued in three (6.8%)
      patients, corticosteroids administered to four (9.1%) patients, and
      hospitalization required in 12 (27.3%) patients. Two deaths were attributable to
      IRIS. CONCLUSIONS: IRIS may affect 10% of patients initiating ART in Africa,
      particularly those with advanced immunosuppression, but severe, life-threatening
      IRIS is uncommon.

PMID- 18317002
TI  - Evidence for different susceptibility to tipranavir and darunavir in patients
      infected with distinct HIV-1 subtypes.
AB  - BACKGROUND: Tipranavir (TPV) and darunavir (DRV) are potent against protease
      inhibitor (PI)-resistant viruses. Efficacy of these compounds when confronting
      distinct HIV subtypes is not known. METHODS: All clinical specimens from HIV
      positive patients sent to our institution for drug resistance testing between
      1999 and 2006 were analysed. The prevalence of TPV and DRV resistance mutations
      was assessed based on the latest International AIDS Society-USA panel list.
      Phenotypic susceptibility to DRV and TPV was examined in a subset of these
      samples using the PhenoSense assay. RESULTS: A total of 1364 genotypes were
      analysed, including 1178 from individuals infected with clade B (285 drug naive)
      and 186 with non-B subtypes (137 drug naive). The mean number (+/-SD) of DRV
      resistance-associated mutations was higher in clade B than non-B (0.4 +/- 0.9
      versus 0.06 +/- 0.3; P < 0.001), and more frequent among PI-experienced than drug
      naive patients (0.6 +/- 1.02 versus 0.02 +/- 0.21; P < 0.001). In contrast, the
      mean number of TPV resistance-associated mutations was higher in non-B than B
      subtypes (2.7 +/- 1 versus 1.2 +/- 1.6; P < 0.001), regardless of PI experience.
      Susceptibility to TPV and DRV was examined in 29 drug-naive patients infected
      with non-B subtypes (1A, 3C, 2CRF01_AE, 9CRF02_AG, 1CRF12_BF, 3CRF14_BG, 3F and
      7G). All showed susceptibility to DRV and 93% to TPV. Interestingly, two subtype
      F specimens showed reduced TPV susceptibility, with fold-changes of 2.7 and 2.1,
      respectively. CONCLUSIONS: Non-B subtypes show a greater number of TPV resistance
      associated mutations than B viruses, regardless of PI exposure. While HIV clade
      has no influence on DRV susceptibility, some F subtypes may show reduced TPV
      susceptibility.

PMID- 18317003
TI  - HIV transmission risk behavior among HIV-infected adults in Uganda: results of a
      nationally representative survey.
AB  - OBJECTIVE: Evaluate factors associated with HIV transmission risk behavior among
      HIV-infected adults in Uganda. DESIGN: Cross-sectional and nationally
      representative study (2004-2005 Uganda HIV/AIDS Sero-Behavioral Survey) tested
      18,525 adults (15-59 years old) for HIV and herpes simplex virus type 2 (HSV-2).
      METHODS: Data were weighted to obtain nationally representative results. Sexual
      risk behavior by HIV-infected individuals was defined as unprotected sex at last
      encounter. Using multivariate analysis, we identified factors associated with
      being sexually active, knowing HIV status, and using contraception and condoms.
      RESULTS: Of 1092 HIV-infected respondents, 64% were female (median age was 33
      years), 84% had HSV-2, and 13% reported one lifetime partner (1% of men and 23%
      of women). Twenty-one percent of adults knew their HIV status and 9% knew their
      partners'. Seventy-seven percent were sexually active, of whom 27% reported
      condom use at last sex. Of last unprotected sexual encounters, 84% were with
      spouses and 13% with steady partners. Of cohabitating persons, 40% had an HIV
      negative spouse. Those who knew their HIV status were three times more likely to
      use a condom at last sex encounter [adjusted odds ratio (AOR), 3.0; 95%
      confidence intervals (CI), 1.9-4.7] and those who knew their partners' HIV status
      were 2.3 times more likely to use condoms (AOR, 2.3; 95% CI, 1.2-4.3).
      CONCLUSIONS: A minority of HIV-infected adults in Uganda knew they had HIV
      infection; nearly half were in an HIV-discordant relationship, and few used
      condoms. Knowledge of HIV status, both one's own and one's partner's, was
      associated with increased condom use. Interventions to support HIV-infected
      persons and their partners to be tested are urgently needed.

PMID- 18317004
TI  - Transmission of drug-resistant HIV-1 in Europe remains limited to single classes.
AB  - BACKGROUND: The spread of drug-resistant HIV-1 might compromise the future
      success of current first-line regimens. OBJECTIVE: To analyse the extent and
      impact of transmission of drug-resistant HIV-1 variants in Europe. DESIGN AND
      METHODS: The European prospective programme (SPREAD) collected demographic,
      clinical and virological data from 1245 HIV-1-infected individuals in 17
      countries diagnosed in 2002-2003. The potential impact of transmitted drug
      resistance mutations (TDRMs) on therapy response was determined by using
      genotypic interpretation algorithms. RESULTS: The overall prevalence of viruses
      with drug-resistance mutations was 9.1% [96/1050; 95% confidence interval: 7.5
      11.1]. The majority (71%) harboured only a single amino acid substitution with
      limited effect on predicted drug susceptibility. Mutations associated with
      resistance to nucleoside reverse transcriptase inhibitors were observed most
      frequently [57/1050 (5.4%)], followed by mutations related to protease inhibitors
      [32/1050 (3.0%)] and mutations related to non-nucleoside reverse transcriptase
      inhibitors (NNRTIs) [27/1050 (2.6%)]. In some cases, however, resistance was
      quite extensive. Four individuals were infected with viruses with reduced
      susceptibility to all nucleoside reverse transcriptase inhibitors, 3 to all
      protease inhibitors and 20 to both NNRTIs. Remarkably, in one individual, the
      resistance pattern was so extensive that none of the available current
      antiretroviral drugs was predicted to be fully active. CONCLUSION: The prevalence
      of TDRM-HIV is quite prominent (9.1%) but did not increase in comparison with a
      large retrospective European study. Particularly the presence of single NNRTI
      mutations may impact the efficacy of the first-line regimens. Continuous
      prospective monitoring remains indicated to explore the patterns and factors
      contributing to the transmission of TDRMs as well as the potential clinical
      consequences.

PMID- 18317005
TI  - Effects of antiretroviral therapy on semen quality.
AB  - OBJECTIVE: To evaluate the effect of combination antiretroviral therapy (cART) on
      semen quality. DESIGN: A longitudinal cohort study. SETTING: The HIV outpatient
      clinic of the Academic Medical Centre in Amsterdam, the Netherlands. SUBJECTS: A
      cohort of 34 male patients with different estimated duration of HIV-1 infection,
      who were about to start various combinations of cART. INTERVENTION(S): Blood and
      semen analyses before the start of cART and 4, 12, 24, 36 and 48 weeks
      thereafter. MAIN OUTCOME MEASURE(S): We examined the effect of cART on semen
      parameters by a repeated measurements procedure using a mixed-effects model.
      RESULTS: The median period of follow up was 48 weeks (interquartile range 33-52
      weeks). Five patients used thymidine analogue-containing cART, 23 used tenofovir
      based cART, six used other regimens. At all timepoints the percentage of
      progressively motile spermatozoa was low according to WHO criteria, and it
      decreased significantly from 28 to 17% during follow-up (P = 0.02). All other
      semen parameters were in the normal range and remained stable. CONCLUSION: cART
      negatively affected the percentage of progressively motile spermatozoa. Whether
      this reduced motility affects the chances of fathering a child or leads to an
      increased need for artificial reproductive techniques is at present unknown.

PMID- 18317006
TI  - HIV immune reconstitution syndrome in sub-Saharan Africa.

PMID- 18317007
TI  - HAART improves quality of life: should we care about the quality of spermatozoa?

PMID- 18317008
TI  - 4E10 and 2F5 monoclonal antibodies: binding specificities to phospholipids,
      tolerance, and clinical safety issues.

PMID- 18317009
TI  - Improvement in HIV-related endothelial dysfunction using the anti-inflammatory
      agent salsalate: a pilot study.
AB  - We hypothesized that heightened systemic inflammation contributes to the
      increased rate of cardiovascular events in HIV-infected patients not receiving
      combination antiretroviral therapy. We performed a pilot trial to assess the
      effects of the nuclear factor-kappaB inhibitor salsalate on flow-mediated
      dilation of the brachial artery, a measure of endothelial function. Flow-mediated
      dilation significantly improved after 8 weeks of salsalate. However,
      hepatotoxicity occurred frequently. Research using alternative agents is
      warranted to examine the role of inflammation in HIV-related cardiovascular
      disease.

PMID- 18317010
TI  - Upregulation of PD-L1 on monocytes and dendritic cells by HIV-1 derived TLR
      ligands.
AB  - Increased PD-L1 expression has been reported in HIV-1-infected individuals, but
      the mechanisms leading to PD-L1 upregulation remain to be elucidated. Here we
      demonstrate that HIV-1-derived Toll-like receptor (TLR)7/8 ligands can induce
      MyD88-dependent upregulation of PD-L1 on plasmacytoid dendritic cells, myeloidic
      dendritic cells and monocytes. These data suggest a mechanism through which HIV-1
      derived TLR ligands might contribute to the functional impairment of virus
      specific PD-1-positive T cells by inducing the upregulation of PD-L1 on antigen
      presenting cells.

PMID- 18317011
TI  - Sexually transmitted hepatitis C virus superinfection in HIV/hepatitis C virus co
      infected men who have sex with men.
AB  - We report two cases of sexually transmitted hepatitis C virus (HCV)
      superinfection in HIV/HCV-co-infected patients with high-risk sexual behaviour.
      The two patients had chronic HCV and a history of sexually transmitted
      infections. HCV superinfection was confirmed by phylogenetic analysis. No risk
      factors for HCV were found except unprotected anal sex with multiple casual male
      partners. HCV serology and serum HCV RNA should be examined periodically in HIV
      infected men who have sex with men engaging in high-risk sexual behaviours.

PMID- 18317012
TI  - Life-threatening exacerbation of Kaposi's sarcoma after prednisone treatment for
      immune reconstitution inflammatory syndrome.

PMID- 18317013
TI  - Virological and immunological response to HAART regimen containing integrase
      inhibitors in HIV-2-infected patients.

PMID- 18317014
TI  - Increasing incidence of acute hepatitis C in individuals diagnosed with primary
      HIV in the United Kingdom.

PMID- 18317016
TI  - Methods for the prediction of low-molecular-weight occupational respiratory
      sensitizers.
AB  - PURPOSE OF REVIEW: There is recognition that respiratory sensitization is an
      occupational hazard of high concern. Despite international regulatory
      requirements there is no established protocol for the efficient prospective
      identification of chemical respiratory sensitizers. We review the predictive
      behaviour of available methods and suggest a possible high-throughput protocol.
      RECENT FINDINGS: Animal or in-vitro tests specific to respiratory exposure and
      resulting in direct asthma-related outcomes have not been developed, although the
      use of a local lymph node assay originally designed for skin sensitization has
      been advocated in a respiratory context. Various methods have been used to
      develop quantitative structure-activity relationship models for prediction of low
      molecular-weight organic chemical respiratory sensitizers. The estimated negative
      predictive value for all of the published models is 1, but their differences in
      positive predictive value can be exploited. SUMMARY: The most pragmatic as well
      as valid approach for screening large numbers of industrial chemicals for
      respiratory sensitization hazard is likely to consist of an algorithm starting
      with quantitative structure-activity relationship models. Further corroboration
      from animal or human data, however, may be required for chemicals with a positive
      result by quantitative structure-activity relationship.

PMID- 18317017
TI  - Exposure-response in occupational allergy.
AB  - PURPOSE OF REVIEW: This review examines the relationship between exposure to
      workplace allergens and the risk of developing occupational allergy. RECENT
      FINDINGS: Evidence suggests that the risk of developing occupational allergy
      increases with allergen exposure; however, with some occupational allergens, this
      exposure-response relationship is more complex. In laboratory animal workers, the
      risk of developing occupational allergy increases with exposure, except at high
      allergen exposure when there is a reduction in sensitization. This attenuation of
      specific immunoglobulin E antibody is associated with increased specific
      immunoglobulin G4 antibodies, which are likely to play a protective role, leading
      to a form of natural tolerance. Exposure-response relationships are also very
      dependent on the genetic susceptibility of the individual. The interaction
      between genes, occupational allergens and other cofactors in the environment,
      such as endotoxin, are also important risk factors in the development of
      sensitization and asthma. SUMMARY: Occupational allergy provides a good
      opportunity to understand the complex relationships between exposure to allergens
      in the workplace, interaction with genes and the coexposures with other factors
      in the working environment and the increased risk of developing occupational
      allergy.

PMID- 18317018
TI  - Lung/skin connections in occupational lung disease.
AB  - PURPOSE OF REVIEW: Exposure to occupational and environmental agents can cause a
      spectrum of lung diseases that are predominantly immune-mediated. Research and
      prevention have focused primarily on the respiratory tract. Recent studies,
      however, suggest that the skin may also be an important route of exposure and
      site of sensitization. This article highlights key findings, focusing on
      isocyanate asthma and chronic beryllium disease. RECENT FINDINGS: Occupational
      lung diseases such as isocyanate asthma and chronic beryllium disease continue to
      occur despite reduced airborne exposures. Although challenging to quantify,
      recent studies have documented isocyanate and beryllium skin exposure, even with
      the use of personal protective clothing. Factors that impair skin barrier
      function, such as trauma, may promote sensitization to such agents. Animal
      studies demonstrate that skin exposure to isocyanates and protein allergens is
      highly effective at inducing sensitization, with subsequent inhalation challenge
      eliciting asthmatic responses. Limited clinical studies suggest a similar role
      for human skin exposure to certain sensitizing agents. SUMMARY: Recent findings
      support a greater focus on the role of skin exposure in the development of
      certain occupational and environmental lung diseases. Although further research
      is needed, it is prudent to reduce both skin and inhalation exposures.

PMID- 18317019
TI  - The role of innate immunity in occupational allergy: recent findings.
AB  - PURPOSE OF REVIEW: Discovery of a system of pattern recognition receptors has
      opened an entirely new field in inflammation research. This paper reviews studies
      from the last 18 months focusing on mechanisms of immune stimulation after
      exposure to microbial components and other exposures that induce or modulate
      innate immune responses. RECENT FINDINGS: Perhaps the most studied pattern
      recognition receptor response pathway is endotoxin upregulation of cytokine
      production via lipopolysaccharide binding protein (LBP), soluble and membrane
      bound CD14, v-myb-dependent gene 2 (MD-2) and toll-like receptor (TLR) 4. This
      interaction, and that of synthetic TLR2-agonist (Pam3Cys4) with toll-like
      receptors TLR1 and TLR2, has recently been characterized at the structural level,
      and has been confirmed by a blunted response in knockout mice. Dectin-1
      recognizes the hyphal form, but not the spores of Aspergillus fumigatus, giving
      the first known function of the dectin receptor. Martinez has hypothesized that
      inconsistencies relating to the protective effect of lipopolysaccharide exposure
      on allergy might be explained by a gene-environment interaction. SUMMARY: We are
      on the brink of understanding the complex nature and interaction of the pattern
      recognition receptors and the cellular events following their binding of ligands.
      Further elucidation of gene-environment interactions will probably lead to
      important discoveries in the near future.

PMID- 18317020
TI  - Immunology of chronic beryllium disease.
AB  - PURPOSE OF REVIEW: This review discusses the immunology of chronic beryllium
      disease. It addresses the importance of the interaction between class II
      molecules and the T cells that recognize beryllium, along with the subsequent
      immune response that results in sensitization and disease, and genetic factors
      leading to variation in this response. RECENT FINDINGS: HLA-DPB1 with a glutamic
      acid at amino acid position 69 (Glu69) confers increased risk of beryllium
      sensitization and is not specific for chronic beryllium disease. The degree of
      negative surface charge of the molecule may increase risk of chronic beryllium
      disease but not sensitization. In the absence of Glu69, HLA-DRB1 alleles may
      function in beryllium presentation, increasing the risk of chronic beryllium
      disease. The T-cell response as assessed by the beryllium lymphocyte
      proliferation test is dependent on central memory T-cells, while Th1 cytokine
      secretion leading to granulomatous inflammation and chronic beryllium disease is
      dependent on the activity of effector memory T cells. Polymorphisms in cytokine
      genes, such as the TGF-beta1 gene, also affect the risk of chronic beryllium
      disease and more severe disease. SUMMARY: The current diagnostic criteria for
      sensitization and chronic beryllium disease rely on the beryllium lymphocyte
      proliferation test. By understanding the novel immunologic mechanisms and genetic
      factors associated with sensitization and chronic beryllium disease, we may
      improve our ability to detect beryllium health effects with new diagnostics, and
      hopefully refine therapies for disease.

PMID- 18317021
TI  - Mechanisms of increased airway sensitivity to occupational chemicals and odors.
AB  - PURPOSE OF REVIEW: Airway symptoms induced by chemicals and odors are common
      problems that are also reported after contact with substances normally regarded
      as nontoxic. This article reviews current findings and opinions regarding
      mechanisms of increased airway sensitivity to occupational chemicals and odors.
      RECENT FINDINGS: Individuals exposed to organic solvents during work had more
      nasal irritation and lower threshold to pyridine odor compared with a nonexposed
      control group. Six percentage of a general population in Sweden had pronounced
      airway chemical sensitivity and augmented capsaicin cough sensitivity, known to
      reflect the sensory nerve reactivity of the airways. The cough sensitivity was
      associated with changed levels of nerve growth factor in nasal lavage and such
      patients had longstanding symptoms influencing their working capacity. Positron
      emission tomography activation studies with several different odorants showed in
      patients with odor-associated symptoms an odorant-related increase in activation
      of the anterior cingulate cortex and cuneus-precuneus in comparison with a
      control group. SUMMARY: In subgroups of individuals with airway symptoms induced
      by chemicals and odors, there seems to be a sustainable physiological mechanism
      behind the reactions. An increased vulnerability to stress cannot be neglected as
      a confounding factor in some sensitive individuals.

PMID- 18317022
TI  - Variability in the diagnosis of occupational asthma and implications for clinical
      practice.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide a summary of recent
      evidence relating to occupational asthma diagnosis. RECENT FINDINGS: Recent
      evidence suggests that whilst prolonged asthmagen exposure worsens the prognosis,
      many steps in the diagnostic process are problematic for workers with possible
      occupational asthma. Certain workers suffer delay prior to specialist assessment,
      and assessment itself may be of variable quality. Emerging evidence suggests that
      whilst experts agree about certain aspects of case assessment, there is still
      likely to be variation in clinical practice. Implications of this variation for
      the workers assessed are relatively under researched. SUMMARY: Future research
      needs to focus not only on improving diagnostic testing, but also on improving
      consistency and agreement over diagnosis.

PMID- 18317023
TI  - Rhinitis and its impact on work.
AB  - PURPOSE OF REVIEW: Health-related work disability has been increasingly
      recognized as an important component of the economic and societal burden of a
      disease. The purpose of this review is to summarize recently published data
      pertaining to the impact of rhinitis on work disability. RECENT FINDINGS: Recent
      studies have investigated the impact of rhinitis on both the amount of time
      missed from work (absenteeism) and the level of work effectiveness while on the
      job (presenteeism). These studies have shown that rhinitis has a rather modest
      effect on absenteeism, with estimated productivity losses of approximately 1-4%
      resulting from missed work time. By contrast, rhinitis is associated with
      substantial impairment in at-work performance. Estimates of lost productivity
      attributable to reduced on-the-job effectiveness ranged from 11 to 40%. The
      impact of rhinitis on work productivity is affected by symptom severity, and
      allergen exposure, and it can be reduced by second-generation antihistamines.
      SUMMARY: The impact of rhinitis on work productivity should be further
      characterized and taken into account for establishing cost-effective management
      strategies.

PMID- 18317024
TI  - Role of respiratory viral infections in the development of atopic conditions.
AB  - PURPOSE OF REVIEW: Respiratory viral infections are implicated in both protection
      from, and inception of, allergic airway disease. Severe lower respiratory tract
      viral infections are associated with recurrent wheeze, asthma and atopy. It is
      unclear if this association is causal and the underlying mechanisms governing
      this are unknown. Whilst respiratory viral infections are the major precipitants
      of acute exacerbations of wheezing illness, early life infections are also
      clearly associated with protection from allergic diseases. This article aims to
      review the current understanding of the complex relationship between lower
      respiratory tract viral infections and their impact upon development of atopy in
      the airway. RECENT FINDINGS: Clinical studies and animal models have further
      demonstrated that lower respiratory tract viral infections are strongly
      associated with development of recurrent wheeze and asthma with human
      rhinoviruses being shown to be the most prevalent cause of lower respiratory
      tract viral infections in infants, along with associated asthma development. A
      case-control study provided evidence of a contributory role for respiratory viral
      infections within this association, whilst recent experimental studies provide a
      possible mechanistic insight. SUMMARY: Progress into understanding the
      relationship between respiratory viral infections and allergic airway disease is
      essential for development of treatments aimed at treating common risk factors
      mediating association but not cause. Recent findings may have begun to identify
      key pathways open to therapeutic intervention.

PMID- 18317025
TI  - Pediatric biomarkers in asthma: exhaled nitric oxide, sputum eosinophils and
      leukotriene E4.
AB  - PURPOSE OF REVIEW: Markers of disease status that provide a numerical measure of
      disease activity, biomarkers, have come into more routine use in medicine. This
      is evidenced by troponin and brain natriuretic peptide when measuring cardiac
      function or glomerular filtration rate in relation to kidney function. Similar
      markers to assess inflammation in the asthmatic lung have emerged as possible
      tools to guide treatment. Three biomarkers, fractional exhaled nitric oxide,
      sputum eosinophils and leukotriene E4 in the urine and exhaled breath condensate,
      have been heavily investigated. RECENT FINDINGS: Recent literature indicates that
      exhaled nitric oxide, sputum eosinophils and leukotriene E4 in the urine, and
      exhaled breath condensate could serve as good markers of inflammation in the
      asthmatic airway. These markers, when combined with conventional measures of lung
      function--forced expiratory flow in 1 s, peak flow or methacholine challenge-
      will be of benefit in improving asthma control in the pediatric population.
      SUMMARY: Exhaled nitric oxide and urinary leukotriene E4 are relatively easy to
      attain in the clinical setting. Sputum eosinophils are an excellent tool for
      assessing inflammation, however sputum induction can be challenging for a young
      child. Despite small limitations, all three biomarkers are potentially valuable
      when used in conjunction with conventional methods for airway control.

PMID- 18317026
TI  - Management of asthma in preschool children with inhaled corticosteroids and
      leukotriene receptor antagonists.
AB  - PURPOSE OF REVIEW: The aim of this article is to review the recently published
      studies addressing various treatment approaches for asthma in preschool children.
      RECENT FINDINGS: The heterogeneity of wheezing in the preschool years complicates
      the study of asthma in this age group. Once children at highest risk for
      persistence of wheezing are identified, various management strategies may be
      thoroughly studied. Several recent studies have confirmed the efficacy and safety
      of both inhaled corticosteroids and leukotriene receptor antagonists in the
      management of early childhood asthma. In addition to examining clinical efficacy,
      studies investigating the effects of these treatment modalities on the underlying
      airway inflammation have recently increased in number and quality and confirm the
      anti-inflammatory actions of these therapeutic strategies in the preschool child
      with asthma. SUMMARY: Evidence for the preferred treatment strategies for
      persistent asthma in young children remains incomplete. Based on the current body
      of evidence, there is rationale for further investigation of these management
      strategies, including direct comparisons between inhaled corticosteroids and
      leukotriene receptor antagonists, as well as the role of long-acting beta
      agonists, potentially targeting the subpopulations of early childhood with
      wheezing who are at highest risk for persistence of asthma symptoms.

PMID- 18317027
TI  - Long-term effects of asthma medications in children.
AB  - PURPOSE OF REVIEW: This review describes recent studies in children that
      evaluated long-term outcomes of controller asthma medications. RECENT FINDINGS:
      The literature is replete with studies demonstrating the immediate profound
      effects of inhaled corticosteroids on symptom control, reduction in morbidity and
      mortality rates, improvement in lung function, bronchial hyperresponsiveness, and
      inflammatory markers. Recent evidence supports that even this most effective
      class of medication does not alter the progression of recurrent wheeze to asthma,
      and that its effects on decline in lung function are limited. The lack of
      evidence supporting the superiority of lower dose inhaled corticosteroids
      combined with a long-acting beta-agonist over a full dose inhaled corticosteroid
      with respect to long-term efficacy measures and growth effects suggests that
      monotherapy with acceptable inhaled corticosteroid dose is the preferred
      treatment in children with mild to moderate persistent asthma. Montelukast has
      been shown to significantly reduce asthma exacerbations and lower use of
      supplemental inhaled corticosteroids compared with placebo. SUMMARY: There is
      mounting evidence that the currently available medications for childhood asthma
      have a substantial impact on multiple dimensions of asthma control. No drug in
      our current armamentarium, however, has been found to alter the natural
      progression of childhood asthma nor halt progressive airway damage in the more
      susceptible children.

PMID- 18317028
TI  - Pharmaceutical treatment strategies for childhood asthma.
AB  - PURPOSE OF REVIEW: Although great improvement has been obtained in quality of
      life and mastering of illness by asthmatic children over recent decades,
      controversies still exist related to asthma treatment. The objective of the
      present article is to discuss such controversies. RECENT FINDINGS: Results from
      recent publications related to childhood asthma treatment question existing
      dogmas. Important for prescribing correct treatment to children is correct
      diagnosis. Phenotypes of childhood asthma related to treatment decisions are
      discussed. Early use of inhaled steroids in young children is still debated as
      well as the preference of inhaled long-acting beta2-agonists versus leukotriene
      receptor antagonists as add on to inhaled steroids. When present, both allergic
      rhinitis and asthma should be treated to obtain improved control. Also as regards
      the treatment of exercise-induced asthma in children, new results concerning use
      of leukotriene receptor antagonists is discussed as well as the acute treatment
      in infants with bronchial obstruction. SUMMARY: There are still several
      controversies regarding treatment of the asthmatic child. New studies designed
      specifically for children are needed to solve these questions. One cannot rely on
      studies performed in adults for treatment in children. New studies designed for
      childhood asthma are needed to solve these controversies.

PMID- 18317030
TI  - Bibliography. Current world literature. Occupation disease.

PMID- 18317029
TI  - The role of written action plans in childhood asthma.
AB  - PURPOSE OF REVIEW: The aim of this article is to examine the evidence for the
      effectiveness of a written action plan as an important element of guided self
      management and to identify key features associated with its effectiveness in
      children and adolescents. RECENT FINDINGS: Various written action plans are
      available for use; however, few have been specifically designed or validated for
      children. Strong, but limited pediatric evidence confirms that the addition of a
      written action plan to guided self-management education significantly improves
      outcome. Use of daily controller medication, with no step-up therapy other than
      as needed inhaled beta2-agonist, best prevents asthma exacerbations. Symptom
      based appear superior to peak-flow based written action plans. The paucity of
      pediatric trials does not permit the identification of other keys features that
      enhance the dispensing of written action plans by healthcare professionals or
      uptake of recommendations by children, adolescents and their parents. SUMMARY:
      Written action plans are effective tools to facilitate self-management. While
      step-up therapy is not superior to daily controller medication, symptom-based are
      superior to peak-flow based action plans for preventing exacerbations, other keys
      features associated with effectiveness have yet to be identified.

PMID- 18317032
TI  - Outbreaks of sporotrichosis.
AB  - This article examines the reasons for clusters of cases or outbreaks of
      sporotrichosis such as the Brazilian outbreak described in this issue of Current
      Opinion in Infectious Diseases. It highlights areas that require elucidation such
      as the infectivity of yeast phase fungi in relation to other outbreaks. It then
      describes phenotypic variations seen with Sporothrix schenckii that could
      contribute to pathogenesis and enhanced infectivity of fungi in the environment.

PMID- 18317033
TI  - Management of common bacterial infections of the skin.
AB  - PURPOSE OF REVIEW: Bacterial skin infections commonly encountered in the
      community include impetigo, folliculitis/furunculosis, simple abscesses,
      erysipelas and other nonnecrotizing cellulitis. The review focuses on recent
      epidemiological, bacteriological and therapeutic advances. RECENT FINDINGS:
      Impetigo and erysipelas occur in about 20 and 1 person/1000/year, respectively.
      Main risk factors for erysipelas are toe-web intertrigo and lymphedema. The true
      incidence of furunculosis is unknown, whereas outbreaks in small communities are
      reported worldwide. Staphylococcus aureus is the predominant pathogen for
      impetigo and furunculosis, and methicillin-resistant strains play a growing role
      in both diseases. Erysipelas are mainly caused by streptococci, whereas local
      complications (i.e. abscesses or blisters) may be due to staphylococci, including
      methicillin-resistant strains in involved geographic areas. Recent trends for
      treating impetigo and furunculosis predate community-acquired methicillin
      resistant S. aureus. For outbreaks of furunculosis, stringent decolonization
      measures are showing promise, whereas there is no validated therapeutic regimen
      for chronic furunculosis. Current trends for erysipelas involve ambulatory
      treatments and reduced duration of antibiotics. SUMMARY: Despite better
      epidemiological or bacteriological knowledge of common bacterial skin infections,
      the exact role of methicillin-resistant staphylococci needs regular surveys in
      involved geographic areas. Antibiotic treatment must be active on staphylococci
      and, to a lesser degree, on streptococci.

PMID- 18317034
TI  - Epidemic sporotrichosis.
AB  - PURPOSE OF REVIEW: Epidemic sporotrichosis is rare and has been related to an
      environmental source of infection. There were no reports of epizootics before a
      cat-transmitted epidemic was reported in Rio de Janeiro, Brazil. In the present
      paper we review the data published on this epidemic. RECENT FINDINGS: From 1998
      to 2004, 759 humans, 64 dogs and 1503 cats were diagnosed with sporotrichosis in
      the Evandro Chagas Clinical Research Institute. Of them, 85% of dogs and 83.4% of
      patients were reported to have had contact with cats with sporotrichosis, and
      55.8% of the latter reported cat bites or scratches. Unusual manifestations were
      diagnosed in humans. Canine sporotrichosis presented as a self-limited mycosis.
      Feline sporotrichosis varied from subclinical infection to severe systemic
      disease with hematogenous dissemination of Sporothrix schenckii. Sporotrichosis
      in cats always preceded its occurrence among their owners and their domiciliary
      canine contacts. The zoonotic potential of cats was demonstrated by the isolation
      of S. schenckii from skin lesion fragments, and from material collected from
      their nasal and oral cavities. SUMMARY: Thus far it is not known why
      sporotrichosis takes on the proportion of an emergent zoonosis in Rio de Janeiro.
      We alert physicians and veterinarians working outside the epidemic area to the
      diagnostic challenges involved with sporotrichosis.

PMID- 18317035
TI  - Immunization and dermatophytes.
AB  - PURPOSE OF REVIEW: Despite the availability of effective vaccines for certain
      animal species, vaccination against dermatophytosis requires improvement and
      further development in both animals and humans. This review provides an update on
      the current situation and focuses on recent advances in host-dermatophyte
      relationships that could have implications for future vaccination against the
      most prevalent of the fungal diseases. RECENT FINDINGS: Numerous dermatophytic
      virulence factors have recently been isolated and characterized at the molecular
      level, notably secreted proteases involved in the invasion of the keratin
      network. Their precise roles in the different steps of the infectious process and
      in immunopathogenesis are being studied, while all aspects of the host immune
      response against dermatophytes, including the innate response, are becoming
      increasingly documented. In addition, new molecular tools are now available for
      studying dermatophytes, which will accelerate research on this topic. SUMMARY:
      The growth of knowledge concerning all aspects of the host-dermatophyte
      relationship should contribute towards sound strategies for the development of
      effective and safe vaccines against dermatophytosis.

PMID- 18317036
TI  - Epidermodysplasia verruciformis and human papilloma virus.
AB  - PURPOSE OF REVIEW: Despite its rarity, epidermodysplasia verruciformis was
      addressed in depth in recent literature. Patients are afflicted by persistent
      human papillomavirus infections and develop cutaneous malignancies more
      frequently and younger than in the general population. The disease is therefore
      considered a model for a viral role in cutaneous oncogenesis, although
      implication is controversial. We focus on recent findings in genetics, highlight
      multiple viewpoints regarding the role of epidermodysplasia verruciformis-human
      papillomavirus in nonmelanoma skin cancer and other diseases, and discuss
      treatment strategies. RECENT FINDINGS: Susceptibility loci for epidermodysplasia
      verruciformis were mapped and encoded protein functions are becoming better
      understood, but a unified genetic theory for epidermodysplasia verruciformis is
      lacking. Epidermodysplasia verruciformis-human papillomavirus, originally thought
      present only in epidermodysplasia verruciformis, is now considered ubiquitous,
      its role still being elucidated. Numerous therapies for epidermodysplasia
      verruciformis lesions were proposed, although there is no consensual first-line
      treatment strategy. SUMMARY: Discoveries of novel mutations and further study of
      epidermodysplasia verruciformis-human papillomavirus in lesional and nonlesional
      skin of epidermodysplasia verruciformis patients and the general population may
      generate a cohesive theory regarding a viral role in cutaneous oncogenesis.
      Future understanding of the disease may yield an optimal approach to treating
      epidermodysplasia verruciformis patients.

PMID- 18317037
TI  - Community-associated methicillin-resistant Staphylococcus aureus skin infections:
      advances toward identifying the key virulence factors.
AB  - PURPOSE OF REVIEW: In recent years there has been an increase in the incidence of
      community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA)
      infections in healthy individuals, the cause of which is largely unknown. CA-MRSA
      primarily causes skin and soft-tissue infections but certain strains are also
      associated with unusually severe pathology. The purpose of this review is to
      provide a critical analysis of our current knowledge of virulence factors
      contributing to skin and soft-tissue infections caused by CA-MRSA. RECENT
      FINDINGS: Isolates classified as pulsed-field gel electrophoresis type USA300
      have emerged as the predominant CA-MRSA genotype and in most geographic areas
      account for 97% or more of CA-MRSA infections. Recent key studies, such as those
      reporting the complete genome sequence of USA300, and the discovery of cytolytic
      peptides that contribute significantly to CA-MRSA virulence, lead the way for
      future investigations. SUMMARY: Although we have only a cursory understanding of
      the molecular mechanisms of CA-MRSA virulence, studies using clinically relevant
      CA-MRSA isolates are beginning to identify virulence determinants specific to
      this pathogen. Identifying CA-MRSA virulence determinants and the concerted
      regulation of these factors will foster development of vaccines and therapeutics
      designed to control CA-MRSA skin infections.

PMID- 18317038
TI  - Cowpox virus infection: an emerging health threat.
AB  - PURPOSE OF REVIEW: Human cowpox, a rare zoonotic infection, evokes a self-limited
      disease, except for immunocompromised and eczematous patients, particularly
      children, where it can become severe. The causative agent, cowpox virus, is
      distributed in Europe, west former USSR, and adjacent areas of Northern and
      Central Asia, with an increasing number of reports in Europe. The purpose of this
      paper is to review cowpox with an emphasis on its epidemiology and management.
      RECENT FINDINGS: Numerous reports of human cowpox affecting young people in
      Europe indicate that lack of smallpox vaccination, which has been abandoned since
      1977, may render the population more vulnerable to cowpox virus. The ownership of
      wild and exotic animal pets is becoming more popular, and the range of recognized
      wild and domestic animal hosts is expanding, SUMMARY: Cowpox as a human emerging
      zoonotic hazard raises public health concerns as well as a question about the
      production of effective vaccine and antiviral agents.

PMID- 18317039
TI  - Serum markers in community-acquired pneumonia and ventilator-associated
      pneumonia.
AB  - PURPOSE OF REVIEW: This article reviews recent data on the usefulness of serum
      markers in community-acquired pneumonia and ventilator-associated pneumonia. The
      focus is on clinical studies, with an emphasis on adult critically ill patients.
      RECENT FINDINGS: Serum markers have demonstrated potential value in early
      prediction and diagnosis of pneumonia, in monitoring the clinical course and in
      guiding antibiotic therapy. C-reactive protein appears to perform better in
      diagnosing infection, because several studies have shown that procalcitonin may
      remain undetectable in some patients, specifically those with pneumonia.
      Procalcitonin exhibited a better correlation with clinical severity, however.
      Furthermore, one report demonstrated the efficacy and safety of procalcitonin
      guided antibiotic therapy in community-acquired pneumonia. SUMMARY: Serum markers
      should only be used as a complementary tool to support the current clinical
      approach. Use of serum markers, in particular procalcitonin and C-reactive
      protein, represents a promising strategy in the clinical decision-making process
      in patients in whom pneumonia is suspected. Specifically, these markers can be
      used to guide culture sampling and empirical antibiotic prescription, and to
      monitor the clinical course, adjust the duration of antibiotic therapy and
      identify nonresponders, in whom an aggressive diagnostic and therapeutic approach
      may prevent further clinical deterioration.

PMID- 18317040
TI  - Bronchiectasis: new findings in the pathogenesis and treatment of this disease.
AB  - PURPOSE OF REVIEW: Bronchiectasis is an under-appreciated cause of chronic lung
      disease in the USA. We highlight developments in diagnosis and treatment of this
      debilitating disease. RECENT FINDINGS: A possible link between gastroesophageal
      reflux and development of nontuberculous mycobacterial lung disease was
      highlighted. Reflux is more common in patients with nontuberculous mycobacterial
      lung disease, and among those with established bronchiectasis more extensive
      disease was observed in those patients who also had reflux. Long-term mortality
      in bronchiectasis was significantly associated with age, lower body mass index,
      dyspnea, lack of vaccination, hypoxemia, hypercapnia, and other functional
      parameters. In a large, randomized clinical trial, addition of inhaled tobramycin
      to ciprofloxacin for acute exacerbations of Pseudomonas infection produced
      microbiologic improvement correlating with clinical outcomes but not overall
      improvement. A review noted that five macrolide trials reported reduced sputum
      volume, improved lung function, and better symptom control. Finally, articles
      suggested benefit from inhaled hyperosmolar agents (e.g. hypertonic saline and
      inhaled mannitol). SUMMARY: The possible link between gastroesophageal reflux and
      nontuberculous mycobacterial lung disease, and the microbiology and resistance
      patterns of bacteria observed in these patients were clarified. A large study of
      inhaled tobramycin for exacerbations was inconclusive, but macrolide therapy and
      hyperosmolar agents hold promise.

PMID- 18317041
TI  - What is healthcare-associated pneumonia and how is it managed?
AB  - PURPOSE OF REVIEW: Pneumonia developing before hospital admission in patients in
      close contact with the health system was recently termed 'healthcare-associated
      pneumonia' and proposed as a new category of respiratory infection. We focus on
      the recent literature concerning the epidemiology, causative organisms,
      antibiotic susceptibilities, and outcomes of and empirical antibiotic therapy for
      this condition. RECENT FINDINGS: The reported incidence of healthcare-associated
      pneumonia among patients requiring hospitalization for pneumonia ranges from 17%
      to 67%. Hospitalization within 90 days before pneumonia, attending a dialysis
      clinic and residing in a nursing home were the most common criteria for
      healthcare-associated pneumonia. Compared with patients with community-acquired
      pneumonia, those with healthcare-associated pneumonia are older, have greater co
      morbidity, and are more likely to have aspiration pneumonia and pneumonia caused
      by antibiotic-resistant pathogens. Patients with healthcare-associated pneumonia
      also more frequently initially receive an inappropriate antibiotic therapy, have
      higher case fatality rates and have longer hospital stay. SUMMARY: Many patients
      hospitalized with pneumonia via the emergency department have healthcare
      associated pneumonia. There are significant differences in the spectrum of
      causative organisms and antibiotic susceptibilities between healthcare-associated
      and community-acquired pneumonia. Physicians should differentiate patients with
      healthcare-associated pneumonia from those with community-acquired pneumonia to
      promote a targeted approach when selecting initial antibiotic therapy.

PMID- 18317042
TI  - Diagnosis of ventilator-associated pneumonia: is there a gold standard and a
      simple approach?
AB  - PURPOSE OF REVIEW: Diagnosis of ventilator-associated pneumonia remains
      controversial. Different approaches are advocated, but none has yet demonstrated
      superiority. Diagnosis based on clinical data and aetiological diagnosis of
      ventilator-associated pneumonia episodes are two concepts that should be combined
      in an integrative evaluation for ventilator-associated pneumonia. Recent findings
      in diagnosis are reviewed here. RECENT FINDINGS: Studies of various diagnostic
      strategies have been conducted to evaluate whether they influence outcome.
      Strategies include use of biomarkers (e.g. C-reactive protein and procalcitonin)
      and use of clinical scores to render the diagnostic process more objective. The
      appropriateness of the available aetiological diagnostic techniques and their
      reliability in the absence of a 'gold standard' for diagnosis were also recently
      addressed. It remains controversial whether type of culture (quantitative or
      nonquantitative) or sampling method (invasive or noninvasive) influences
      aetiological diagnosis or outcomes in ventilator-associated pneumonia. It is
      unlikely that any single approach is the optimal diagnostic assessment whenever
      ventilator-associated pneumonia is suspected. SUMMARY: Microbiological data
      should always be used in association with clinical data when assessing patients
      with suspected ventilator-associated pneumonia. Integration of these data might
      be the most simple and effective strategy for diagnosing ventilator-associated
      pneumonia.

PMID- 18317043
TI  - Selective decontamination of the digestive tract.
AB  - PURPOSE OF REVIEW: The aim of this article is to review relevant studies on the
      topic of selective decontamination of the digestive tract published in 2006 and
      2007. RECENT FINDINGS: The only recently published randomized controlled
      selective decontamination of the digestive tract study failed to demonstrate a
      benefit of selective decontamination on survival among trauma patients. In fact,
      two new meta-analyses of selective decontamination of the digestive tract studies
      were presented: one demonstrated reduced incidences of Gram-negative bacteraemia;
      in the other no reduction in fungaemia was found. Although selective
      decontamination of the digestive tract has been associated with increased
      selection of methicillin-resistant Staphylococcus aureus (MRSA), transmission of
      MRSA was controlled in a Spanish unit when using selective decontamination in
      combination with topical vancomycin. Several randomized studies and one meta
      analysis suggest that oropharyngeal decontamination with antiseptics is also
      highly effective in preventing respiratory tract infection in critically ill
      patients. SUMMARY: The evidence that selective decontamination of the digestive
      tract improves patient outcome in mixed ICU patients is still based upon meta
      analysis and two single centre studies in MRSA-naive settings. Larger and
      preferably multicentre studies are needed to confirm these observations. Further
      remaining questions are whether oropharyngeal decontamination alone is as
      effective as the full selective decontamination of the digestive tract regimen
      and whether selective decontamination could be applied successfully in settings
      with high levels of antibiotic resistance.

PMID- 18317044
TI  - Respiratory infection complicating HIV infection.
AB  - PURPOSE OF REVIEW: Respiratory infections remain a major cause of morbidity among
      HIV-infected persons. Thus, knowledge of recent advances regarding HIV-associated
      opportunistic pneumonias is crucial for optimal care of HIV-infected persons.
      RECENT FINDINGS: Bacterial pneumonia is the most common HIV-associated
      opportunistic pneumonia in the USA and its incidence remains appreciable.
      Worldwide, tuberculosis dominates the clinical picture. The absence of rapid,
      affordable diagnostics for active and latent tuberculosis remains a major
      obstacle that must be overcome if the global epidemic is to be slowed. The
      specter of extensively drug resistant tuberculosis and its overlap with HIV
      infection highlight the importance of rapid diagnostics and the need for
      accessible drug susceptibility testing. Pneumocystis (carinii) jirovecii
      pneumonia appears to be a more common pneumonia among HIV-infected persons
      residing in developing countries than was previously appreciated. Similar to
      tuberculosis, the absence of available diagnostics in developing areas is a major
      obstacle to clinical care and epidemiologic studies. The critical care of HIV
      infected persons is challenging. SUMMARY: Although tremendous advances have been
      made in our understanding of the management, treatment, and prevention of HIV and
      its associated respiratory infections, significant gaps remain. Thus, continued
      epidemiologic, clinical, and bench research is needed.

PMID- 18317045
TI  - New British and American guidelines for the antibiotic prophylaxis of infective
      endocarditis: do the changes make sense? A critical review.
AB  - PURPOSE OF REVIEW: The British Society for Antimicrobial Chemotherapy and the
      American Heart Association have radically revised their guidelines for the
      antibiotic prophylaxis of endocarditis. This review discusses the evidence behind
      the most controversial changes and considers possible future developments. RECENT
      FINDINGS: The new guidelines emphasize good oral hygiene for preventing viridans
      streptococcal endocarditis. Antibiotic prophylaxis for dental procedures is only
      recommended for patients with the highest-risk cardiac conditions. American Heart
      Association guidelines no longer recommend prophylaxis for urological and
      gastrointestinal procedures. SUMMARY: While only up to 6% of endocarditis cases
      may be prevented by antibiotic prophylaxis there is controversy as to what to
      recommend for the individual cardiac patient undergoing a given procedure. The
      new guidelines about dental prophylaxis are based on epidemiological studies that
      failed to include sufficient subjects undergoing specific interventions. When
      considering viridans streptococcal rather than total bacteraemia rates, asserting
      that the prevalence of bacteraemia after invasive dental procedures is similar to
      that after toothbrushing may be incorrect. The British Society for Antimicrobial
      Chemotherapy report probably overestimates the risk of fatal anaphylaxis after an
      oral dose of amoxicillin. In contrast, the American Heart Association guidelines
      comment on the absence of any reports of fatal anaphylaxis associated with the
      antibiotic prophylaxis of endocarditis.

PMID- 18317046
TI  - Current world literature.

PMID- 18317047
TI  - Percutaneous humeral plating of fractures of the proximal humerus: results of a
      prospective multicenter clinical trial.
AB  - OBJECTIVES: To evaluate the safety and functional outcome of a recently described
      surgical technique of percutaneous plating for proximal humerus fractures.
      DESIGN: Prospective clinical trial. SETTING: : Two urban Level 1 university
      trauma centers. PATIENTS: From February 2002 to December 2003, 34 consecutive
      patients underwent surgery by 5 trauma surgeons from 2 teaching hospitals. Twenty
      seven patients had 1-year follow-up. INTERVENTION: The technique involved 2
      minimal incisions with a lateral deltoid split and a more distal shaft incision.
      A proximal humerus-specific locking plate was implemented. MAIN OUTCOME
      MEASUREMENTS: DASH (disabilities of the arm, shoulder, and hand) and Constant
      Murley evaluation scores were used for functional evaluation. The presence of
      complications was noted. RESULTS: Specifically, there were no axillary nerve
      injury injuries and no loss of reduction. The average Constant score at 1 year
      was 82 and the DASH score was 26. CONCLUSION: This study demonstrated that the
      functional outcome results correspond to a normal age-adjusted score signifying
      an acceptable result.

PMID- 18317048
TI  - Early complications in proximal humerus fractures (OTA Types 11) treated with
      locked plates.
AB  - PURPOSE: To examine our incidence of early complications that occur using the
      Proximal Humeral Internal Locking System (PHILOS) and to determine the
      contributing factors. SETTING: Academic medical center. PATIENTS: Fifty-one
      consecutive patients treated with a proximal humerus locking plate. OUTCOME:
      Development of an intraoperative, acute postoperative, or delayed postoperative
      complication. METHODS: A retrospective analysis was undertaken of a consecutive
      series of proximal humerus fractures treated with a locking plate between
      February 2003 and January 2006 at our institution. Fifty-one fractures or
      fracture nonunions were identified in 18 male and 33 female patients with an
      average age of 61. All acute injuries were treated with a similar protocol of
      open reduction internal fixation with the PHILOS plate followed by early range of
      shoulder motion. Nonunions were treated in a similar manner with the addition of
      iliac crest bone graft placement. Patients were objectively assessed on their
      outcome by physical as well as radiological examination. All complications were
      recorded. Statistical analyses were performed to determine if patient age,
      fracture type, or number of screws placed in the humeral head contributed to
      complications. RESULTS: Fifty-one patients were available for minimum 6-month
      follow-up (mean, 16 months; range, 6 to 45 months). Radiographically, 92% of the
      cases united at 3 months after surgery, and 2 fractures had signs of
      osteonecrosis at latest follow-up. Sixteen complications were seen in 12 patients
      (24%). Eight shoulders in eight patients (16%) had screws that penetrated the
      humeral head. Two patients developed osteonecrosis at latest follow-up. One acute
      fracture and one nonunion failed to unite after index surgery. Significant
      heterotopic bone developed in 1 patient. Early implant failure occurred in 2
      patients; one was revised to a longer plate, and one underwent resection
      arthroplasty. There was one acute postoperative infection. CONCLUSION: The major
      complication reported in this study was screw penetration, suggesting that
      exceptional vigilance must be taken in estimating the appropriate number and
      length of screws used to prevent articular penetration; although the device
      provides exceptional fixation stability, its indication must be scrutinized for
      each individual patient, taking the extent of trauma/fracture and age into
      consideration and carefully weighing it against other forms of treatment.

PMID- 18317049
TI  - Acetabular fracture patterns and their associated injuries.
AB  - OBJECTIVES: Characterize relationships between acetabular fractures patterns and
      visceral organ injuries. DESIGN: Retrospective review. SETTING: : University
      medical center. PATIENTS/PARTICIPANTS: Three hundred twenty-three patients with
      displaced acetabular fractures identified in a prospectively maintained database.
      INTERVENTION: Acetabular fractures were classified according to force vector at
      the time of injury. Posterior wall, posterior column, and posterior
      column/posterior wall injuries were assumed to have been caused by an axial load.
      The remaining seven acetabular fracture types were assumed to have resulted from
      a lateral or trochanteric load. Records were reviewed to establish any
      relationship between acetabular fracture patterns defined by their force vector
      and injuries to other skeletal and nonskeletal organ systems. MAIN OUTCOME
      MEASUREMENTS: Comparison of organ injury end points of additional skeletal
      injury; bowel, bladder, brain, kidney, liver, spleen, and lung injury;
      retroperitoneal hematoma; and vascular injury of the pelvis. Data were analyzed
      using chi-square, with statistical significance defined as P < 0.05. RESULTS:
      Acetabular fractures resulting from lateral loads had a statistically higher
      association with retroperitoneal hematomas (P < 0.001), spleen (P < 0.008), liver
      (P < 0.002), vascular (P < 0.001), kidney (P < 0.001), and bladder (P < 0.001)
      injuries than did posteriorly directed acetabular fractures. Transverse posterior
      wall fractures exhibited intermediate characteristics between axial load and the
      remaining lateral load patterns. CONCLUSIONS: Direction of force is important in
      the etiology of nonskeletal injury patterns. The possibility of additional
      nonskeletal injury increases from the rates seen in axial load patterns to those
      in lateral load patterns involving the anterior column.

PMID- 18317050
TI  - The effect of suture pattern and tension on cutaneous blood flow as assessed by
      laser Doppler flowmetry in a pig model.
AB  - OBJECTIVE: To determine the effects of various suture patterns on cutaneous blood
      flow (CBF) at the wound edge as increasing tension is applied through the suture.
      METHODS: Four different suture patterns commonly used for wound closure (simple,
      vertical mattress, horizontal mattress, and Allgower-Donati) were placed
      individually after a full-thickness incision was made in an anesthetized pig. A
      laser Doppler flowmeter (LDF) was placed on the skin edge after the suture was
      passed. Baseline CBF was recorded. Increasing tension was applied to the wound
      edge via the suture through a tensionometer in 0.5-lb (0.23-kg) increments from 0
      to 2.5 lb (1.13 kg). CBF was then recorded as a function of tension for each
      suture pattern. RESULTS: The Allgower-Donati suture pattern affected CBF
      significantly less than the other three suture patterns did for all tensions from
      0.5 to 2.0 lb (0-0.9 kg; P < 0.05). There were no significant differences between
      vertical mattress, horizontal mattress, and simple suture patterns. CONCLUSIONS:
      The Allgower-Donati suture pattern had the least effect on CBF with increasing
      tension in this model. Further study is warranted on the benefits of this suture
      pattern because it may decrease wound complications in traumatized tissues.

PMID- 18317051
TI  - Frequency and fracture morphology of the posteromedial fragment in bicondylar
      tibial plateau fracture patterns.
AB  - OBJECTIVES: Bicondylar tibial plateau fracture management remains therapeutically
      challenging, partly because of multiplanar articular comminution. This study was
      performed to evaluate the frequency and morphologic characteristics of the
      posteromedial fragment in this injury pattern. DESIGN: Retrospective chart and
      radiographic review. SETTING: Urban Level 1 university trauma center. PATIENTS:
      Fifty-seven patients sustaining 57 Orthopedic Trauma Association (OTA) C-Type
      bicondylar tibial plateau fractures formed the study group. MAIN OUTCOME MEASURE:
      Between May 2000 and March 2003, 170 OTA C-Type bicondylar tibial plateau
      fractures were identified using an orthopaedic database. One hundred and forty
      six fractures had computed tomographic (CT) scans performed prior to definitive
      fixation and were reviewed using the Picture Archiving and Communication System
      (PACS). Sixty-six (45.2%) injuries had fractures that involved the medial
      articular surface. Nine with suboptimal CTs were excluded, leaving 57 injuries
      for review. Forty-two patients demonstrated coronal plane posteromedial
      fragments. Morphologic evaluation of the posteromedial fragment included
      articular surface area, maximum posterior cortical height (PCH), and sagittal
      fracture angle (SFA). RESULTS: Forty-two of 57 injuries (74%) demonstrated a
      posteromedial fragment that comprised a mean of 58% of the articular surface of
      the medial tibial plateau (range, 19%-98%) and a mean of 23% of the entire tibial
      plateau articular surface (range, 8%-47%). Mean posteromedial fragment height was
      42 mm (range, 16-59 mm), and mean sagittal fracture angle was 81 degrees (range,
      33 degrees to 112 degrees). Six patients demonstrated fracture patterns not
      accurately identified by the AO/OTA (Arbeitsgemeinschaft fur
      Osteosynthesefragen/Orthopaedic Trauma Association) fracture classification
      system. CONCLUSIONS: A posteromedial fragment was observed in nearly one third of
      the bicondylar plateau fractures evaluated. The morphologic features of this
      fragment may have clinical implications when using currently available laterally
      applied fixed-angle screw/plate implants to stabilize these injuries. Alternate
      or supplementary fixation methods may be required when managing this injury
      pattern.

PMID- 18317052
TI  - Combined single-stage osseous and soft tissue reconstruction of the tibia with
      the Ilizarov method and tissue transfer.
AB  - OBJECTIVE: To determine the outcome of single-stage soft tissue and osseous
      reconstruction using the Ilizarov method and soft-tissue transfer. DESIGN: A
      retrospective review. SETTING: : A university-affiliated, tertiary-care center.
      PATIENTS/INTERVENTION: We identified 11 patients from a retrospective review from
      January 1994 to July 1999 who underwent single-stage soft tissue and osseous
      reconstruction using the Ilizarov method. All 11 patients had an initial
      traumatic mechanism to their tibia and had previous operative intervention before
      the combined procedure. The Ilizarov procedure was performed for infected tibial
      nonunion (8 cases), or complex fracture with soft-tissue loss (3 cases). MAIN
      OUTCOME MEASUREMENTS: Soft tissue transplant survival, union, range of motion,
      leg length discrepancy, the Association for the Study and Application of the
      Method of Ilizarov (ASAMI) score, radiographic parameters. RESULTS: There were 8
      concomitant free tissue flaps and 3 local pedicled flaps. Two patients had
      primary bone grafting, and 5 others had addition of an antibiotic impregnated
      bone substitute. There were 8 cases of elective reconstructive surgery and 3
      cases of acute traumatic fracture. The mean duration of Ilizarov application was
      26 weeks (range, 7 to 42). Eight tibiae united primarily, and 3 healed after
      delayed bone grafting. There were 2 major flap complications. Both were
      successfully managed with repeat surgery. One patient sustained a repeat open
      fracture and subsequently received an amputation. According to the ASAMI score,
      there were 9 excellent results, 1 good result, and 1 poor result. CONCLUSION: Our
      study suggests that concomitant osseous and soft-tissue reconstruction with the
      Ilizarov technique and free or pedicled flaps is a viable option for patients
      with composite tissue defects.

PMID- 18317053
TI  - A comparison of optical and electromagnetic computer-assisted navigation systems
      for fluoroscopic targeting.
AB  - OBJECTIVES: Freehand targeting using fluoroscopic guidance is routine for
      placement of interlocking screws associated with intramedullary nailing and for
      insertion of screws for reconstruction of pelvic and acetabular injuries. New
      technologies that use fluoroscopy with the assistance of computer guidance have
      the potential to improve accuracy and reduce radiation exposure to patient and
      surgeon. We sought to compare 2 fluoroscopic navigation tracking technologies,
      optical and electromagnetic versus standard freehand fluoroscopic targeting in a
      standardized model. INTERVENTION: Three experienced orthopaedic trauma surgeons
      placed 3.2-mm guide pins through test foam blocks that simulate cancellous bone.
      The entry site for each pin was within a circular (18-mm) entry zone. On the
      opposite surface of the test block (130-mm across), the target was a 1-mm
      diameter radioopaque spherical ball marker. Each surgeon placed 10 pins using
      freehand targeting (control group) navigation using Medtronic iON StealthStation
      (Optical A), navigation using BrainLAB VectorVision (Optical B), or navigation
      using GE Medical Systems InstaTrak 3500 system (EM). OUTCOME MEASUREMENTS: Data
      were collected for accuracy (the distance from the exit site of the guidewire to
      the target spherical ball marker), fluoroscopy time (seconds), and total number
      of individual fluoroscopy images taken. RESULTS: The 2 optical systems and the
      electromagnetic system provided significantly improved accuracy compared to
      freehand technique. The average distance from the target was significantly (3.5
      times) greater for controls (7.1 mm) than for each of the navigated systems
      (Optical A = 2.1 mm, Optical B = 1.9 mm EM = 2.4 mm; P < .05). Accuracy was
      similar for the 3 navigated systems, (P > 0.05). The ability to place guidewires
      in a 5-mm safe zone surrounding the target sphere was also significantly improved
      with the optical systems and the EM system (99% of wires in the safe zone)
      compared to controls (47% in the safe zone) (P < 0.002). Safe zone placement was
      similar among the 3 navigated systems (P > 0.05). Fluoroscopy time (seconds) and
      number of fluoroscopy images were similar among the three navigated groups (P >
      0.05). Each of these parameters was significantly less when using the computer
      guided systems than for freehand-unguided insertion (P < 0.01). CONCLUSIONS: Both
      optical and electromagnetic computer-assisted guidance systems have the potential
      to improve accuracy and reduce radiation use for freehand fluoroscopic targeting
      in orthopaedic surgery.

PMID- 18317054
TI  - Indirect medial reduction and strut support of proximal humerus fractures using
      an endosteal implant.
AB  - Fractures of the proximal humerus, particularly in osteoporotic bone, are still
      frequently referred to as unsolved fractures. The recent explosion of locking
      plate technology has included these fractures, but it appears that laterally
      placed locking plates may not be as predictable as hoped. Medial column
      mechanical support of these fractures may play a significant role in the ultimate
      stability of fixation during rehabilitation until healing occurs. We have devised
      a technique of using a segment of fibula allograft, placed endosteally and
      incorporated into the locking construct, to aid in the reduction and restoration
      of the mechanical integrity of the medial column of the proximal humerus.

PMID- 18317055
TI  - The medial approach for arthroscopic-assisted fixation of lateral tibial plateau
      fractures: patient selection and mid- to long-term results.
AB  - Arthroscopy has been used in the fixation of tibial plateau fractures for more
      than 20 years. Although not proved in randomized trials, several authors using
      the arthroscopic technique have demonstrated results comparable to traditional
      methods, using open reduction and internal fixation with standard buttress
      plates. Improved rehabilitation, greater range of motion, and a shortened
      hospital stay for patients who have undergone this technique have also been
      reported.

PMID- 18317056
TI  - Nonconcentric reduction by an inverted anterosuperior labrum with avulsed
      osteocartilaginous fragment in an anterior hip dislocation.
AB  - A 26-year-old man was involved in a motorcycle accident and presented with an
      anterior hip dislocation. After a closed reduction, the hip showed a
      nonconcentric reduction. With an open reduction, an inverted anterosuperior
      labrum with avulsed osteocartilage was found, which prohibited the concentric
      reduction of the hip joint. The inverted labrum, cartilage, and torn ligamentum
      teres were excised, the femoral head was reduced, and the capsule was
      reapproximated. Six months after surgery, the patient still complained of slight
      pain in the left hip, with 20- to 30-degree restriction of hip flexion relative
      to that of the normal side. A radiograph of the hip was normal.

PMID- 18317057
TI  - Irreducible fracture-dislocation of the ankle caused by an entrapped medial
      malleolus at the syndesmosis.
AB  - A 55-year-old fisherman sustained an unusual and irreducible fracture-dislocation
      of the ankle joint. An entrapped medial malleolar fragment was discovered by
      computed tomography between the distal tibia and lateral malleolus. The fragment
      was removed during an emergent open reduction, during which deltoid ligament
      repair and internal fixation of the bimalleolar fracture were undertaken. At the
      18-month follow-up visit, the patient was working normally and was asymptomatic.
      At previous visits, he demonstrated a full range of ankle motion and had normal
      radiograph.

PMID- 18317059
TI  - To the editor: Navigated femoral nailing using noninvasive registration of the
      contralateral intact femur to restore anteversion. Technique and clinical use.

PMID- 18317061
TI  - Indolent lung cancers--time for a paradigm shift: a review.
AB  - The present paradigm is that slow-growing and clinically unimportant lung cancers
      are very rare. Over the years, convincing evidence for their existence in
      significant numbers has been dismissed, but with computerized tomography scanning
      being increasingly common, their reality can no longer be denied. The time is now
      ripe for a paradigm shift--with consequences for screening as well as clinical
      practice in the future. The doubling time of the tumor is probably the most
      important factor for survival of the patient, and research on how to measure this
      figure is urgent. Age, smoking habits, and comorbidities of the patient are now
      the main factors when discussing treatment with the patient; once we can predict
      the behavior of the cancer, i.e., whether it is indolent or actually threatens
      the patient's life, we will be able to give better advice.

PMID- 18317062
TI  - Role of chromosome 3q amplification in lung cancer.
AB  - Chromosome abnormalities often correlate with molecular abnormalities and provide
      a starting point for gene discovery and characterization in the context of a
      specific disorder. In cancer biology, chromosomal abnormalities carry diagnosis,
      prognostic, and predictive value of response to treatment. Recently,
      methodologies such as array comparative genomic hybridization and oligonucleotide
      microarrays allow discovery of regions of frequent alterations with high
      resolution. Genomic gain at chromosome 3q location has been recognized as one the
      most prevalent and significant alterations in lung cancer. Emerging data suggests
      that regions of amplification have profound effect on tumor development and house
      candidate biomarkers of disease progression, response to therapy and prognosis.
      This review examines how genome-wide analysis of lung cancer lead to the
      evaluation of a specific genomic alteration on chromosome 3q, the study of
      candidate driver genes and their potential clinical implications.

PMID- 18317063
TI  - Validation study of the proposed IASLC staging revisions of the T4 and M non
      small cell lung cancer descriptors using data from 23,583 patients in the
      California Cancer Registry.
AB  - BACKGROUND: We performed a validation study of the proposed International
      Association for the Study of Lung Cancer (IASLC) tumor, node, metastasis (TNM)
      and stage grouping revisions on advanced nonbronchioloalveolar carcinoma (non
      BAC) non-small cell lung cancer (NSCLC). METHODS: Twenty-three thousand five
      hundred eighty-three patients from the California Cancer Registry between 1999
      and 2003 with histologically confirmed non-BAC NSCLC and complete TNM staging
      were identified and reclassified according to the IASLC proposed TNM revisions
      and new stage groupings. Twelve thousand nine hundred one stage IIIB and IV
      patients formed the primary analysis of the changes to T4 and M descriptors.
      Surveillance, Epidemiology, and End Results extent of disease codes were used to
      identify various T4 and M descriptors. Cox proportional hazards regression was
      used to calculate hazard ratios (HRs) among the stage groupings of the current
      and proposed staging system with adjustment for ethnicity, gender, age,
      histology, histologic grade, socioeconomic status, surgery, radiation, and
      chemotherapy. RESULTS: The proposed changes to the T4 and M descriptors were
      supported by overall survival analysis. T4 due to additional nodules had
      significant survival advantage over other T4 and M descriptors among non-BAC
      NSCLC and individual histology and warrants down-staging to T3. Pericardial
      effusion had survival similar to M1b patients. Cox proportional hazards
      regression analysis supports subdividing M descriptor into M1a (versus IASLC
      stage IA; HR = 4.90; 95% confidence interval: 4.49-5.34) and M1b (versus IASLC
      stage IA; HR = 6.84; 95% confidence interval: 6.30-7.44). CONCLUSIONS: IASLC has
      greatly improved the T4 and M descriptors allowing better prognostication of
      advanced non-BAC NSCLC. Pericardial effusion may be considered as M1b rather than
      M1a.

PMID- 18317064
TI  - Zoledronic acid and survival in patients with metastatic bone disease from lung
      cancer and elevated markers of osteoclast activity.
AB  - INTRODUCTION: Bone metastases from non-small cell lung cancer (NSCLC) are
      associated with skeletal-related events (SREs) and elevated levels of N
      telopeptide of type I collagen (NTX) in some patients. Zoledronic acid (ZOL)
      reduces SRE risk and NTX levels. METHODS: To assess effects of baseline
      variables, including NTX levels (normal = NTX < 64 nmol/mmol creatinine; high =
      NTX > or = 64 nmol/mmol creatinine), on treatment effects in NSCLC patients, a
      retrospective analysis was performed in NSCLC patients with bone metastases (N =
      382) treated with ZOL or placebo every 3 weeks in a 21-month randomized clinical
      trial in patients with NSCLC or other solid tumors. Cox proportional hazards
      models assessed relative risks (RRs) of SREs, bone lesion progression, and death.
      Multivariate models analyzed covariate effects on survival. RESULTS: For both
      placebo- and ZOL-treated patients, high baseline NTX correlated with increased
      SRE risk (p = 0.068 and 0.012, respectively). Although high versus normal
      baseline NTX correlated with more than twofold increased risks of bone lesion
      progression and death in the placebo group (p = 0.039 and 0.001, respectively),
      correlations were weaker in the ZOL group (RR = 1.38; p = 0.0186 and RR = 1.27; p
      = 0.142, respectively), suggesting an interaction effect of ZOL and baseline NTX.
      Among patients with high baseline NTX, ZOL significantly reduced the RR of death
      by 35% versus placebo (p = 0.024). Per multivariate analysis, ZOL treatment (p =
      0.005), higher lymphocyte count (p = 0.011), performance status 0 to 1 (p =
      0.012), and absence of narcotic use (p = 0.016) correlated with improved
      survival. CONCLUSIONS: This retrospective analysis revealed statistically
      significant correlations between ZOL and increased survival versus placebo in
      NSCLC patients and high baseline NTX levels.

PMID- 18317065
TI  - Ethnic differences in the management of lung cancer in New Zealand.
AB  - BACKGROUND: Major ethnic disparities in lung cancer survival exist in New
      Zealand, with Maori having a higher case-fatality ratio than non-Maori. AIM: To
      assess whether secondary care management of lung cancer differed by ethnicity and
      could contribute to ethnic survival disparities. METHODS: An audit of secondary
      care management in Auckland and Northland of lung cancer patients diagnosed in
      2004 permitted comparison of the management of lung cancer in different ethnic
      groups. RESULTS: The 565 eligible cases comprised: European 378 (67%), Maori 95
      (17%), Pacific Peoples 56 (10%), Asian 23 (4%), and other or unknown ethnicity 13
      (2%). In multivariate analysis (adjusting for tumor and patient factors including
      comorbidity), Maori were 2.5 times more likely to have locally advanced disease
      than localized disease compared with Europeans (p < 0.01), and four times less
      likely to receive curative rather than palliative anticancer treatment compared
      with Europeans (p < 0.01). Maori had longer transit times from diagnosis to
      treatment (p < 0.001). Maori were more likely to decline treatment and miss
      appointments than Europeans, although this only partially explained management
      differences. CONCLUSION: Multiple factors are potentially responsible for the
      higher case-fatality ratio in Maori. Such factors include presentation with more
      advanced disease, lower rates of curative treatment for nonmetastatic disease,
      and longer transit times from diagnosis to treatment. In this retrospective
      study, socioeconomic deprivation, comorbidity levels, and failure to accept
      treatment did not fully explain ethnic differences in management. Further
      assessment of the underlying issues by prospective evaluation is warranted.

PMID- 18317066
TI  - The yield of endoscopic ultrasound in lung cancer staging: does lymph node size
      matter?
AB  - INTRODUCTION: Transoesophageal endoscopic ultrasound with fine-needle aspiration
      (EUS-FNA) is a minimally invasive procedure to demonstrate unresectability in
      lung cancer patients with enlarged malignant mediastinal lymph nodes (MLN). We
      compared the performance of EUS-FNA to show malignant invasion in enlarged versus
      small MLN. METHODS: A single center analysis was performed in lung cancer
      patients with a suspicion for malignant MLN invasion based on the available
      imaging. In these patients, EUS-FNA was presumed to impact the diagnostic course
      since patients underwent surgical-pathologic verification only when EUS-FNA did
      not demonstrate MLN invasion. RESULTS: We evaluated 100 lung cancer patients in
      whom MLN invasion was presumed based on the available imaging. In 75 patients
      (75%), there was at least one enlarged MLN, whereas in 25 patients (25%), only
      small MLN were found. The sensitivity and negative predictive value to detect
      malignancy in enlarged MLN was 96% (95% confidence interval [CI], 87-99) and 67%
      (95% CI, 29-92), respectively. The sensitivity and negative predictive value of
      EUS-FNA in small MLN was 93% (95% CI, 66-99) and 92% (95% CI, 61-99),
      respectively. EUS-FNA prevented a surgical (mediastinal) intervention in 88 and
      52% of the patients with enlarged or small MLN, respectively (p < 0.001).
      CONCLUSIONS: As the sensitivity to detect malignant MLN invasion is comparably
      high for both enlarged and small but suspected MLN, clinicians should consider
      EUS-FNA even in case computed tomography-scan shows no enlarged MLN. The impact
      of EUS-FNA to avoid surgical mediastinal interventions is greater when enlarged
      MLN are present. The moderate negative predictive value of EUS-FNA makes surgical
      pathologic verification still compulsory, regardless of the size of the MLN.

PMID- 18317067
TI  - Induction chemotherapy with carboplatin, irinotecan, and paclitaxel followed by
      high dose three-dimension conformal thoracic radiotherapy (74 Gy) with concurrent
      carboplatin, paclitaxel, and gefitinib in unresectable stage IIIA and stage IIIB
      non-small cell lung cancer.
AB  - INTRODUCTION: Combined modality therapy is a standard therapy for patients with
      unresectable stage III non-small cell lung cancer (NSCLC). Gefitinib is active in
      advanced NSCLC, and in preclinical models, it potentiates the activity of
      radiation therapy. We investigate the tolerability of gefitinib in combined
      modality therapy in combination with three-dimensional thoracic conformal
      radiation therapy (3-dimensional TCRT). METHODS: Stage III patients with a good
      performance status were treated with induction chemotherapy (carboplatin area
      under the curve [AUC] of 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2)
      days 1 and 22) with pegfilgrastim support followed by concurrent chemotherapy
      (carboplatin AUC 2, and paclitaxel 45 mg/m(2) weekly) and gefitinib 250 mg daily
      beginning on day 43 with 3-dimensional TCRT to 74 Gy. RESULTS: Between March 2004
      and January 2006, 23 patients received treatment on the trial: median age 62
      years (range 44-82), 52% female, 61% stage IIIA, 61% performance status 0, 17% >
      or =5% weight loss, and 91% underwent positron emission tomography staging.
      Induction chemotherapy with pegfilgrastim support was well tolerated and active
      (partial response rate, 24%; stable disease, 76%; and early progression, 0%).
      Twenty-one patients initiated the concurrent chemoradiation, and 20 patients
      completed therapy to 74 Gy. The primary toxicities of concurrent chemoradiation
      were grade 3 esophagitis (19.5%) and cardiac arrhythmia (atrial fibrillation)
      (9.5%). The median progression-free survival and overall survival were 9 months
      (95% confidence intervals [CI]: 7-13 months) and 16 months (95% CI: 10-20
      months), respectively. CONCLUSIONS: Treatment with induction chemotherapy and
      gefitinib concurrent with 3-dimensional TCRT has an acceptable toxicity and
      tolerability, but the survival results were disappointing.

PMID- 18317068
TI  - Dual inhibition of the epidermal growth factor receptor with cetuximab, an IgG1
      monoclonal antibody, and gefitinib, a tyrosine kinase inhibitor, in patients with
      refractory non-small cell lung cancer (NSCLC): a phase I study.
AB  - PURPOSE: To determine the optimal doses of the antiepidermal growth factor
      receptor (anti-EGFR) monoclonal antibody cetuximab and the EGFR tyrosine kinase
      inhibitor gefitinib when administered as a combination for patients with
      advanced/metastatic non-small cell lung cancer (NSCLC) previously treated with
      platinum-based chemotherapy. PATIENTS AND METHODS: Patients with
      advanced/metastatic NSCLC treated with prior platinum-based chemotherapy received
      escalating doses of weekly cetuximab (100, 200, and 250 mg/m(2), IV) and fixed
      doses of gefitinib (250 mg/d, PO) until disease progression or unacceptable
      toxicity. Available tumor samples were analyzed for EGFR expression, EGFR gene
      copy number and mutations, and K-RAS mutations. RESULTS: Thirteen patients were
      enrolled in three cohorts. Treatment was generally well-tolerated at all doses.
      One grade 3 headache, observed on the first treatment cycle was initially
      considered dose-limiting toxicity (DLT); this event was eventually determined to
      be caused by a brain metastasis, not toxicity. Three cases of grade 3/4
      hypomagnesemia and 1 case of grade 3 skin rash occurred in the highest-dose
      cohort. Grade 1/2 infusion reactions occurred in three patients without requiring
      treatment discontinuation. Four patients (31%) achieved stable disease, no
      responses were observed. None of the patients had EGFR mutations or gene
      amplification in their tumor samples. CONCLUSION: Dual EGFR inhibition with
      cetuximab and gefitinib is feasible; the combination can be safely administered
      and may have modest activity in advanced/metastatic NSCLC. Cetuximab 250 mg/m(2)
      weekly IV and gefitinib 250 mg/d PO is the recommended phase II dose, although
      the potential for late-onset hypomagnesemia warrants close monitoring of patients
      receiving this combined dosage.

PMID- 18317069
TI  - Thymic carcinoma: 30 cases at a single institution.
AB  - INTRODUCTION: Thymic carcinoma is a rare and invasive mediastinal neoplasm that
      often metastasizes. It constitutes a heterogeneous group of tumors that displays
      different biologic behavior and prognosis. The clinical prognostic factors and
      treatment of thymic carcinoma are not yet standardized. METHODS: Thirty patients
      with thymic carcinoma have been treated at Nagoya City University Hospital since
      1983. The clinical and pathologic data of these patients were retrospectively
      reviewed. Thirteen cases were considered to be unresectable or inoperable and
      received chemotherapy or chemoradiotherapy. Seventeen cases underwent resection;
      total in 7 cases and subtotal in 10 cases. Postoperative irradiation was added as
      adjuvant therapy in the tolerable cases. The most recent five cases received
      induction chemotherapy. RESULTS: In 17 of the 30 cases, the patients died. The
      survival periods in the death cases were from 2.4 to 78.1 months (mean, 32.4
      months; median, 21.0 months). The observation periods in the 13 live cases were
      6.3 to 232 months (average follow-up, 64.6 months). The 5-year survival rate was
      47.5%, and median survival time (MST) was 49.0 months. Cases that underwent total
      resection showed significantly better prognosis than cases with subtotal
      resection (p = 0.011) and inoperable cases (p = 0.002). The cases that underwent
      subtotal resection showed significantly better prognosis than the inoperable
      cases (p = 0.050). The cases with hematogenous metastasis demonstrated
      significantly poorer prognosis (p = 0.021), but lymphogenous metastasis was not a
      significant predictor of poor prognosis. Only resectability was a significant
      prognostic factor in multivariate Cox regression analysis, and the hazard ratio
      was 5.123. CONCLUSIONS: Resectability was the only prognostic factor in thymic
      carcinoma. We suggest the importance of preoperative precise evaluation to
      exclude unresectable Masaoka stage IVb disease and expect preoperative
      chemotherapy or chemoradiotherapy to improve the respectability.

PMID- 18317070
TI  - Pathologic radioresponse of preoperatively irradiated invasive thymomas.
AB  - BACKGROUND: We have been applying preoperative radiotherapy (RT) to Masaoka stage
      III thymomas intending to make surgical resection more complete by reducing mass
      volume, to prevent possible dissemination caused by surgical manipulation and to
      get better survival as a result. However, the radioresponses vary from tumor to
      tumor. We hypothesized that thymoma is a variable radioresponsive tumor depending
      on pretreatment histology. MATERIALS AND METHODS: Twenty-one of stage III
      thymomas underwent preoperative RT plus surgery followed by postoperative RT
      between 1982 and 2004. Reduction ratios, histopathologic changes according to WHO
      histologic criteria, resectability, long-term survival, and disease control, by
      preoperative RT were analyzed. RESULTS: Pretreatment WHO subtypes were type AB (n
      = 1), B1 (5), B2 (6), B3 (4), and unclassified (5). Sixteen tumors (76.2%)
      decreased in size after preoperative RT with a mean (median) reduction ratio of
      30.8% (27.0%). Type B1or B2 group had higher reduction ratio than type B3 group
      (mean value of 39.7%, 31.8%, and 21.0%, respectively, p < 0.01).
      Histopathologically, lymphocyte diminished markedly in type B1 thymoma, and both
      lymphocyte and epithelial cells diminished in type B2, whereas none of the B3
      tumors showed any histologic change. The values of all the cases is 90.5% in
      complete resection, 19.0% in no combined resection of the adjacent organs, and
      77.6% and 83.6% in overall and disease-free 10-year survival, respectively, and
      these value do not differ according to the WHO histologic criteria. CONCLUSIONS:
      This modality at modest doses was macroscopically and histopathologically
      effective on tumors particularly in WHO B1 and B2 thymomas than WHO B3 thymoma.
      The therapeutic benefit of preoperative RT followed by surgery and postoperative
      RT for stage III thymomas should be defined thoroughly.

PMID- 18317071
TI  - Association between systemic chemotherapy before chemoradiation and increased
      risk of treatment-related pneumonitis in esophageal cancer patients treated with
      definitive chemoradiotherapy.
AB  - BACKGROUND: There is limited information on risk factors for treatment-related
      pneumonitis in esophageal cancer patients. AIM OF THE STUDY: To determine factors
      associated with treatment-related pneumonitis in esophageal cancer patients
      treated with definitive chemoradiotherapy. MATERIALS AND METHODS: We
      retrospectively reviewed clinical data from esophageal cancer patients treated
      with definitive chemoradiotherapy from 2000 to 2003. Demographic, clinical, and
      treatment-related data were collected for all patients. The time to occurrence of
      grade > or =2 pneumonitis was calculated from the end of radiotherapy. Univariate
      analyses were performed to determine the existence of any association between
      patient demographic, clinical, or treatment characteristics and pneumonitis.
      RESULTS: In total, 96 patients were included in the study with a median follow-up
      of 8 months (range, <1-48 months). Among them, 23 patients also received an
      average of two cycles of systemic chemotherapy before the initiation of
      concurrent chemoradiation. The incidence of grade > or =2 pneumonitis was 22% at
      1 year. Systemic chemotherapy before concurrent chemoradiation was significantly
      associated with an increased risk of grade > or =2 pneumonitis (p = 0.003), with
      the 1-year incidence of grade > or =2 pneumonitis for patients with and without
      systemic chemotherapy being 49 and 14%, respectively. No other clinical or
      dosimetric factors investigated were associated with the risk of grade > or =2
      pneumonitis. CONCLUSIONS: Systemic chemotherapy before concurrent chemoradiation
      was significantly associated with an increased risk of grade > or =2 pneumonitis,
      suggesting that induction chemotherapy may have sensitized the lung tissue to
      radiation damage in esophageal cancer patients.

PMID- 18317072
TI  - A novel strategy for treatment of metastatic pulmonary tumors: radiofrequency
      ablation in conjunction with surgery.
AB  - INTRODUCTION: Local treatment that includes surgical resection of metastatic
      pulmonary tumors is controversial because of the biologic features and
      invasiveness of these tumors. We report our experience with a premeditated
      treatment involving combined computed tomography-guided radiofrequency ablation
      and surgical resection in three patients with metastatic pulmonary tumors.
      METHODS: Three patients underwent radiofrequency ablation in conjunction with
      surgical resection. The first was a 67-year-old man with pulmonary metastases of
      bronchial adenoid cystic carcinoma. We performed partial resection of five tumors
      in the right lung and ablated a tumor in the left lung. The second was a 66-year
      old man with pulmonary metastases of renal cell carcinoma. He underwent
      radiofrequency ablation for three tumors in the right upper and middle lobes, and
      right lower lobectomy for tumors in that lobe. The third was a 55-year-old man
      with pulmonary metastases of high-grade sarcoma of the right thigh. We performed
      partial resection of five tumors in the left lung and ablated a tumor in the
      right lung. RESULTS: Two patients had metastatic lesions on both sides of the
      lung; we performed surgical resection on one side and radiofrequency ablation
      contralaterally to avoid bilateral thoracotomy. The third patient underwent
      surgical resection and radiofrequency ablation to avoid highly invasive right
      pneumonectomy. All patients survived for more than 1(1/2) years after combination
      therapy. CONCLUSIONS: Premeditated treatment involving a combination of
      radiofrequency ablation and surgical resection can be a useful option in patients
      with metastatic pulmonary tumors, improving curability and avoiding highly
      invasive procedures.

PMID- 18317073
TI  - What to do with "Surprise" N2?: intraoperative management of patients with non
      small cell lung cancer.
AB  - There is debate about how patients should be managed when malignant involvement
      of mediastinal lymph nodes is encountered at the time of lung resection. A
      comprehensive review of the literature demonstrates that differences in which
      outcomes are reported and how extensively patients were staged preoperatively
      explain much of the conflicting data. Certain negative and positive prognostic
      factors can be defined, but in general the outcomes justify proceeding with
      resection unless it is clear that disease will be left behind. Reasonable
      arguments can be made that the approach should include a mediastinal lymph node
      dissection and adjuvant therapy.

PMID- 18317074
TI  - EGFR inhibitors as first-line therapy in advanced non-small cell lung cancer.
AB  - Tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR),
      erlotinib and gefitinib, are active agents in the treatment of advanced non-small
      cell lung cancer (NSCLC). Although platinum-based doublet chemotherapy remains
      the cornerstone for the first-line treatment of metastatic NSCLC, several phase
      II and III trials have been conducted utilizing EGFR TKIs in this setting.
      Patients with advanced NSCLC who are life long never-smokers, those with EGFR TK
      mutations, and those with bronchioloalveolar cell carcinoma histology seem to
      have promising efficacy with first-line therapy with EGFR TKIs compared with
      unselected groups of patients receiving the same agents. Phase III trials have
      clearly demonstrated no improvement in survival when EGFR TKIs were combined with
      conventional platinum-based doublets, with the exception of subset analysis in
      nonsmokers. This review will summarize the results of clinical trials on
      erlotinib or gefitinib in the first-line treatment of select and unselected
      patients with NSCLC and describe ongoing studies with these agents in NSCLC.

PMID- 18317075
TI  - Adenocarcinoma with epidermal growth factor receptor gene mutations in three
      siblings.
AB  - Sensitivity to an inhibitor of epidermal growth factor receptor (EGFR) kinase
      strongly correlates with EGFR somatic mutations in non-small cell lung cancer.
      These mutations are frequently found in patients with adenocarcinoma, never- or
      light-smokers, women, and East Asians. In this study, we show an aggregation of
      three non-small cell lung cancer cases with EGFR gene mutations in one family.
      The subjects were all female, never- or light-smokers with adenocarcinoma. Two of
      the patients responded to treatment with gefitinib. A genetic study of these
      cases would be useful in elucidating genetic susceptibility to lung cancer in
      persons with EGFR mutations.

PMID- 18317076
TI  - Increased vascular-endothelial growth factor (VEGF) tumor expression and response
      to epidermal growth factor receptor (EGF-R) inhibitor erlotinib in non-small cell
      lung cancer (NSCLC).
AB  - A 37-year-old female never smoker with metastatic large cell carcinoma of the
      lung had a partial response to a second line palliative therapy with the EGF-R
      tyrosine kinase inhibitor erlotinib after platinum based first line therapy
      failed. Molecular analysis of the primary and a liver metastasis did neither find
      any EGF-R mutation nor an EGF-R amplification. However, both the primary and the
      metastasis showed an increased gene expression of vascular-endothelial growth
      factor-A in contrast to normal tissue, which was confirmed by
      immunohistochemistry. To our knowledge, this is the first report about a high
      vascular-endothelial growth factor-A expression in the tumor of a patient
      responding to an EGF-R inhibitor postulating that there might be a link between
      both tyrosine kinase pathways.

PMID- 18317078
TI  - The IASLC Lung Cancer Staging Project: revision proposal of pleural effusion and
      controlateral nodule staging.

PMID- 18317079
TI  - IASLC Lung Cancer Staging Project--a radiologist perspective.

PMID- 18317082
TI  - Third-generation chemotherapy agents in the treatment of advanced non-small cell
      lung cancer: a meta-analysis.

PMID- 18317083
TI  - Randomized clinical trial on the effects of the use of diluted adrenaline
      solution in reduction mammaplasty: same patient, same technique, same surgeon.
AB  - BACKGROUND: Reduction mammaplasty is a very common operation in plastic surgery.
      Efforts have been made to reduce blood loss and to lower morbidity by
      infiltrating the breast with vasoconstrictor agents before resection. This is the
      first randomized clinical trial conducted on the same patient, by the same
      surgeon, and using the same operative technique to compare the effects of dilute
      adrenaline solution infiltration. METHODS: Fifty patients (100 breasts) who
      underwent bilateral simultaneous reduction mammaplasty had 0.9% saline and
      bupivacaine with adrenaline (1:500,000) infiltrated in one breast and 0.9% saline
      and bupivacaine infiltrated in the other breast. RESULTS: There was a significant
      decrease in intraoperative blood loss in breasts infiltrated with adrenaline
      solution (p < 0.0001), with no increase in operating time or complication rate
      compared with breasts that had no adrenaline infiltration. CONCLUSION: The use of
      diluted adrenaline is a safe method of reducing the amount of intraoperative
      bleeding, with no increase in adverse effects.

PMID- 18317084
TI  - Neurofibromatosis: a cause of prepubertal gynecomastia.
AB  - BACKGROUND: Atypical presentations of gynecomastia not associated with obesity
      are often underappreciated. Unilateral manifestation, prepubertal onset, and a
      history of associated disorders may contribute to a unique clinical presentation
      for which the diagnosis and management may remain uncertain. This report reviews
      neurofibromatosis as a cause for atypical presentation of gynecomastia in
      prepubertal boys to help establish guidelines for diagnosis and management.
      METHODS: Six nonobese male patients (body mass index <or=20) had an onset of
      gynecomastia at younger than 9 years and were referred for evaluation between
      June of 1994 and December of 2006. RESULTS: The median age of onset of breast
      enlargement was 7(1/2) years (range, 4 to 8 years). Three had bilateral
      involvement, four had localized involvement of the nipple-areola complex, and two
      had diffusely involved breast tissue. Five of the six patients were African
      American (compared with 20 percent for classic gynecomastia). Median
      postoperative follow-up was 7 years, and all were followed beyond puberty. No
      recurrences were seen, although one patient developed a metachronous lesion in
      the contralateral breast. No patient had an abnormal endocrine metabolic workup.
      CONCLUSIONS: Atypical gynecomastia may present in the prepubertal boy and appears
      more prevalent in African Americans. For neurofibromatosis, it is more likely
      unilateral, can be localized to the nipple-areola complex, or entails diffuse
      breast involvement. An endocrine workup appears to be noncontributory.

PMID- 18317085
TI  - Plastic surgeon's risk acceptance in facial transplantation.
AB  - BACKGROUND: A great deal of ethical debate has accompanied the introduction of
      facial tissue allotransplantation into the clinical arena. Critics contend that
      the risks of lifelong immunosuppression do not justify the benefits of this new
      non-life-saving reconstructive procedure, whereas proponents argue that they do.
      Absent from this debate are the opinions of individuals with real-life
      experiences with the risks and benefits associated with this new treatment.
      METHODS: In this study, the authors question facially disfigured individuals (n =
      33) and the reconstructive surgeons who treat them (n = 45), organ transplant
      recipients (n = 42) and the professionals who manage their immunosuppression
      medication (n = 37), and healthy volunteer controls (n = 148) to determine the
      amount of risk they are willing to accept to receive facial tissue
      allotransplantation. A survey with psychometrically reliable and validated
      questions was administered to the above five groups, and appropriate statistical
      analysis was used to analyze and compare the data within and between groups.
      RESULTS: Of the five groups studied, reconstructive surgeons would accept the
      least amount of risk for a facial tissue allotransplant, followed by transplant
      specialists, then kidney transplant recipients, then facially disfigured
      individuals, and finally healthy control volunteers, who would accept the most
      amount of risk. CONCLUSIONS: The authors' data indicate that reconstructive
      surgeons are the least tolerant of risks compared with the other groups studied
      concerning facial tissue allotransplantation. This is particularly important
      because they are the primary caregivers to facially disfigured patients and, as
      such, will be the ones to lead the effort to move this new reconstructive
      treatment into the clinical arena.

PMID- 18317086
TI  - Is the use of intraoperative heparin safe?
AB  - BACKGROUND: Despite the reliability of microvascular free tissue transfer, flap
      loss remains a significant concern. To improve outcome, various pharmacologic
      agents have been used to prevent microvascular thrombosis. The authors review
      their experience with intraoperative heparin therapy, specifically addressing the
      risks of hematoma, pedicle thrombosis, and flap loss rate. METHODS: Results from
      consecutive free flaps performed over a 3-year period were reviewed using a
      prospectively maintained database. Patients were divided into two groups: group A
      received a bolus of 3000 units of intraoperative heparin 10 minutes before flap
      pedicle ligation; group B did not receive intraoperative heparin. Patient
      demographics, procedure type, diagnosis, adjuvant treatment, and complications
      were recorded. Outcome variables included microvascular thrombosis, total and
      partial flap loss, hematoma, seroma, pulmonary embolism, and death. RESULTS: Four
      hundred seventy patients underwent 505 microvascular free flaps for
      reconstruction of oncologic defects. Reconstructed areas included head and neck
      (n = 288), trunk and breast (n = 151), upper extremity (n = 12), and lower
      extremity (n = 19). Of these, 260 flaps (group A) received an intraoperative
      heparin bolus, and 245 flaps (group B) received no intraoperative heparin bolus.
      There were no statistically significant differences in major and minor
      complications between the two groups (power = 0.85). CONCLUSIONS: Intraoperative
      systemic heparin use has no statistically significant effect on the incidence of
      microvascular thrombosis. In addition, administration of a single dose of
      intraoperative heparin does not increase the rate of hematoma formation or
      prevent microvascular thrombosis. Thus, critical factors for flap survival are
      likely independent of the use of intraoperative anticoagulation.

PMID- 18317087
TI  - Meta-analysis of mandibular distraction osteogenesis: clinical applications and
      functional outcomes.
AB  - BACKGROUND: Mandibular distraction osteogenesis has been used effectively to
      treat syndromic craniofacial deformities. In recent years, its scope of
      application has widened to include treatment of airway obstruction in adults and
      children and nonsyndromic class II mandibular hypoplasia. So far, there has been
      no evidence-based review of mandibular distraction osteogenesis for mandibular
      lengthening. METHODS: Two rounds of searches were performed by two independent
      assessors. The first-round PubMed search used the keywords "mandible" and
      "distraction osteogenesis." In the second-round search, the reference lists of
      the articles were retrieved. For both rounds, abstracts and then full articles
      were reviewed and selected on the basis of a set of inclusion and exclusion
      criteria. RESULTS: The 178 retrieved articles yielded 1185 mandibular distraction
      osteogenesis patients: 539 received unilateral mandibular distraction
      osteogenesis and 646 received bilateral mandibular distraction osteogenesis.
      Mandibular distraction osteogenesis was reported to improve facial asymmetry and
      retrognathia (50.1 percent), correct the slanted lip commissure (24.7 percent),
      and improve or level the mandibular occlusal plane (11.1 percent) in unilateral
      asymmetry cases, whereas bilateral mandibular distraction osteogenesis was shown
      to be effective in preventing tracheostomies for 91.3 percent of neonates or
      infants with respiratory distress, and in relieving symptoms of obstructive sleep
      apnea for 97.0 percent of children and 100 percent of adult patients.
      CONCLUSIONS: Mandibular distraction osteogenesis is effective in treating
      craniofacial deformities, but further clinical trials are required to assess the
      long-term stability and to compare the treatment with conventional treatment
      methods, especially in cases of obstructive sleep apnea or class II mandibular
      hypoplasia.

PMID- 18317088
TI  - Recurrence of synostosis following surgical repair of craniosynostosis.
AB  - BACKGROUND: The incidence of resynostosis after surgical release of synostotic
      suture(s) is not well reported. The authors examined cases of nonsyndromic and
      syndromic craniosynostosis treated with surgical repair and established the rate
      of reoperation for synostosis. METHODS: Charts were retrieved from 119
      consecutive patients treated for craniosynostosis: 62 percent were boys, and 11
      percent were treated for craniofacial dysostosis (Apert syndrome, n = 2; Crouzon
      syndrome, n = 4; Saethre-Chotzen syndrome, n = 5; and other, n = 2). RESULTS:
      Eight patients (6.7 percent) underwent surgery for resynostosis [nonsyndromic,
      six of 106 (5.7 percent); syndromic, two of 13 (15.4 percent)]. Seventy-nine
      patients (66.4 percent) underwent primary surgery before 1 year of age. Analysis
      by age at primary operation yielded significantly lower resynostosis rates (p <
      0.02) when patients younger than 1 year [two of 79 resynostosis cases (2.5
      percent)] were compared with those older than 1 year [six of 40 resynostosis
      cases (15 percent)]. Further stratifications of age at initial operation did not
      yield significance for resynostosis. Four of eight patients who resynostosed had
      raised intracranial pressure, as indicated by lumbar puncture following the
      primary operation. A trend of increasing mean length of hospital stay, estimated
      blood loss, and operative time in the patients who eventually resynostosed was
      observed (data not significant). CONCLUSIONS: Resynostosis rates were higher in
      syndromic than in nonsyndromic children for whom a single suture was involved.
      Analysis of age at primary operation showed an increase in resynostosis when the
      primary operation occurred after age 1 year. Evidence of increased intracranial
      pressure following primary surgery may suggest recurrence.

PMID- 18317089
TI  - A cephalometric analysis of maxillary and mandibular parameters in Treacher
      Collins syndrome.
AB  - BACKGROUND: Treacher Collins syndrome is an autosomal dominant condition of
      varying severity, affecting the tissues of the first and second branchial arches.
      The aim of this article is to present a cephalometric analysis of the
      craniofacial skeleton in Treacher Collins syndrome and provide an age- and sex
      matched comparison as a standard control sample. METHODS: Twenty-four Treacher
      Collins syndrome patients (11 male patients and 13 female patients; mean age,
      17.99 +/- 1.96 years) underwent cephalometric studies, including
      orthopantomography and lateral and anteroposterior cephalography, as part of
      their preparation for bimaxillary surgery. Cephalometric parameters assessing the
      relationships of the skull base, maxilla, and mandible were analyzed and compared
      with age- and sex-matched control data (mean age, 17.75 +/- 1.95 years). RESULTS:
      Cephalometric analysis before orthognathic surgery documented that the Treacher
      Collins syndrome mandible and midface are expectedly short in the anteroposterior
      plane; however, the ratio of maxillomandibular deficiency is particularly
      significant in the female patient. The mandibular plane angle is obtuse,
      affecting female patients in particular, in whom there is also a posteriorly
      placed chin point. Affected individuals have a high antegonial notch height.
      Although the parameters of anterior lower facial height proportion in control and
      syndrome individuals are similar, posterior face height in Treacher Collins
      syndrome is reduced. CONCLUSIONS: This study quantifies the cephalometric
      dysmorphology of patients with Treacher Collins syndrome and compares it to that
      of age-matched controls. These cephalometric characteristics have clinical
      significance in Treacher Collins syndrome and in the planning of bimaxillary
      advancement and genioplasty in syndrome patients.

PMID- 18317090
TI  - The use of alloplastic materials in rhinoplasty surgery: a meta-analysis.
AB  - BACKGROUND: Conventional wisdom regarding the use of alloplastic materials in
      rhinoplastic surgery would advise against their use because of safety and
      aesthetic concerns. However, autogenous tissue harvest is not without associated
      morbidity and may be inadequate or insufficient in some clinical situations.
      Prior studies examining this issue have not provided definitive recommendations
      regarding implant selection, ideal locations in which to use specific implants,
      and necessary follow-up. METHODS: First, the authors systematically reviewed the
      available literature on alloplastic implant use in rhinoplastic surgery by
      searching the MEDLINE database (from 1966 through September of 2005).
      Bibliographies from retrieved articles were searched for additional references.
      All data were independently extracted by two coauthors. Second, the authors
      performed a meta-analysis of the three most commonly used implant types. RESULTS:
      Although a wide variety of alloplastic materials have been used historically and
      are still currently available, the most commonly used materials are silicone,
      expanded polytetrafluoroethylene (Gore-Tex), and porous high-density polyethylene
      (Medpor). In our meta-analysis, the removal rate for both Gore-Tex and Medpor
      implants was 3.1 percent, whereas the removal rate for silicone implants was
      significantly higher at 6.5 percent. CONCLUSIONS: Alloplastic implants in
      rhinoplastic surgery have acceptable complication rates and can be used when
      autogenous materials are unavailable or insufficient. Outcomes with Medpor or
      Gore-Tex implants may be slightly better than those with silicone. Improved
      reporting of implant failures and follow-up times in future studies are needed to
      better define specific guidelines for the use of these materials.

PMID- 18317091
TI  - The importance of advanced cardiac life support certification in office-based
      surgery.
AB  - BACKGROUND: Safety in office-based surgery remains of paramount importance.
      Accordingly, many consider Advanced Cardiac Life Support training a critical
      component of safety preparation for office-based surgery. A survey was recently
      designed and distributed to assess the experience and attitudes of board
      certified plastic surgeons toward Advanced Cardiac Life Support training.
      METHODS: A two-page, 14-question survey was mailed to the 4581 members of the
      American Society of Plastic Surgeons. The anonymous survey consisted of multiple
      choice questions eliciting status of Advanced Cardiac Life Support certification,
      use of office-based surgery, experience with adverse cardiac and respiratory
      events, and opinions on mandating Advanced Cardiac Life Support training.
      RESULTS: The total number of surveys returned was 1461 (32 percent). Current
      Basic Life Support and Advanced Cardiac Life Support certification was 65.6
      percent and 44.9 percent, respectively. Over the past 10 years, 29 percent of
      plastic surgeons participated in a cardiac or respiratory arrest, and 43.9
      percent of these surgeons acted as the code leader; 60.2 percent of plastic
      surgeons felt Advanced Cardiac Life Support certification should be required, but
      only 26 percent of these felt it should be mandated to maintain board
      certification. CONCLUSIONS: Historically, Advanced Cardiac Life Support and
      facility accreditation were strongly recommended but often not required for
      office-based surgery. The American Society of Plastic Surgeons and the American
      Society for Aesthetic Plastic Surgery have taken steps to increase patient
      safety, mandating that outpatient plastic surgery only be performed at accredited
      facilities. Many credentialing organizations are now escalating the requirements
      for Advanced Cardiac Life Support/Basic Life Support certification.

PMID- 18317092
TI  - Barbed sutures: a review of the literature.
AB  - BACKGROUND: Despite substantial mention in the popular press, there is little in
      the plastic surgery or dermatology literature regarding the safety, efficacy,
      longevity, or complications of barbed suture suspension procedures. The authors
      review the literature to estimate several clinical parameters pertaining to
      barbed thread suspensions. METHODS: The authors performed a MEDLINE search using
      the keywords "barbed and suture," "thread and suspension," "Aptos,"
      "Featherlift," and "Contour Thread." RESULTS: The authors identified six studies
      that met their criteria of addressing midface elevation with barbed thread
      suspension. These detected some adverse events, but most of these were minor,
      self-limited, and of short duration. Less clear are the data on the extent of the
      peak correction and the longevity of effect. Objective outcome measures and long
      term follow-up data were not provided in a systematic manner in the few available
      studies. CONCLUSIONS: Suspension of the aging face with barbed sutures offers the
      promise of a minimally invasive technique with diminished adverse events. The
      technique is in its infancy, but it has potential to be a useful and effective
      clinical tool as further innovations are made in the clinic and laboratory.

PMID- 18317093
TI  - Extensor tendon injuries: acute management and secondary reconstruction.
AB  - LEARNING OBJECTIVES: After reviewing the article, the participant should be able
      to: (1) Describe the anatomy of the extensor tendons at the level of the forearm,
      wrist, hand, and fingers. (2) Recognize variations in the anatomy. (3) Master the
      hand examination and define the relevant findings in acute injuries of the
      extensor tendon(s). (4) Delineate the techniques for extensor repair in both
      acute and secondary (delayed) management. SUMMARY: Extension of the fingers is an
      intricate process that reflects the combined action of two independent systems.
      The interossei and lumbricals constitute the intrinsic musculature of the hand.
      These muscles innervated by the median and ulnar nerves extend the proximal
      interphalangeal and distal interphalangeal joints and flex the
      metacarpophalangeal joints. The extrinsic extensors are a group of muscles
      innervated by the radial nerve, originating proximal to the forearm. The
      extrinsic digital extensor muscles include the extensor digitorum communis,
      extensor indicis proprius, and extensor digiti quinti. The digital extensors
      function primarily to extend the metacarpophalangeal joints, but also extend the
      proximal interphalangeal and distal interphalangeal joints. Normal extensor
      physiology reflects a delicate balance between these two unique extensor systems.
      In the injured hand, a functioning intrinsic system may potentially compensate
      for an extrinsic deficit. An understanding of the relevant anatomy and an
      appreciation for the complex interplay involved in extensor physiology is
      necessary to recognize and manage these injuries.

PMID- 18317094
TI  - Selection criteria for the integrated model of plastic surgery residency.
AB  - BACKGROUND: The purpose of this study was to identify those qualities and
      characteristics of fourth-year medical students applying for the Integrated Model
      of Plastic Surgery residency training that will make a successful plastic surgery
      resident. METHODS: A three-part questionnaire was distributed to the training
      program directors of the 20 Integrated Model of Plastic Surgery programs
      accredited by the Residency Review Committee for Plastic Surgery by the
      Accreditation Council on Graduate Medical Education. The first section focused on
      19 objective characteristics that directors use to evaluate applicants (e.g.,
      Alpha Omega Alpha Honor Society membership, United States Medical Licensing
      Examination scores). The second section consisted of 20 subjective
      characteristics commonly used to evaluate applicants during the interview
      process. The third section consisted of reasons why, if any, residents failed to
      successfully complete the training program. RESULTS: Fifteen of the 20 program
      directors responded to the questionnaire. The results showed that they considered
      membership in the Alpha Omega Alpha Honor Society to be the most important
      objective criterion, followed by publications in peer-reviewed journals and
      letters of recommendation from plastic surgeons known to the director. Leadership
      capabilities were considered the most important subjective criterion, followed by
      maturity and interest in academics. Reasons residents failed to complete the
      training program included illness or death, academic inadequacies, and family
      demands. CONCLUSIONS: The authors conclude that applicants who have achieved high
      academic honors and demonstrate leadership ability with interest in academics
      were viewed most likely to succeed as plastic surgery residents by program
      directors of Integrated Model of Plastic Surgery residencies.

PMID- 18317095
TI  - A new and simple marker for the transcartilaginous incision: the Cabas-Coffler
      marker.

PMID- 18317096
TI  - Tip grafts in closed rhinoplasty: insertion and fixation made easy.

PMID- 18317097
TI  - Arterial embolization and skin necrosis of the nasal ala following injection of
      dermal fillers.

PMID- 18317098
TI  - Intraoperative simulation device using negative pressure for construction of
      framework in microtia reconstruction.

PMID- 18317099
TI  - The split ear lobe flap for antihelix reconstruction.

PMID- 18317100
TI  - Can bipolar diathermy enhance scoring in otoplasty? An ex vivo study.

PMID- 18317101
TI  - Retroauricular-calvarial bone island flap transfer to the cheek.

PMID- 18317102
TI  - Power-assisted liposuction treatment of cervicodorsal fat pad in human
      immunodeficiency virus-associated lipodystrophy.

PMID- 18317103
TI  - Intraflap perforator anastomosis in DIEP breast reconstruction: a technique to
      preserve rectus muscle continuity.

PMID- 18317104
TI  - Salvage of an infected breast tissue expander with an implant sizer and negative
      pressure wound management.

PMID- 18317105
TI  - Inverted nipple: use of an effective and personalized splint after surgical
      correction with Pitanguy's technique to avoid relapse of the inversion in 28
      cases.

PMID- 18317106
TI  - Bilateral breast deformity after neonatal tube thoracostomy in fraternal twins.

PMID- 18317107
TI  - Nipple aspirator: a self-designed instrument for inverted nipple.

PMID- 18317108
TI  - Surgical reconstruction of iatrogenic symmastia.

PMID- 18317109
TI  - A new technique to identify leak in tissue expander.

PMID- 18317110
TI  - Chondroma or chondrosarcoma? An indication for sternum resection.

PMID- 18317111
TI  - Coronary spasm as a trigger of acute myocardial infarction in a young patient
      submitted to liposuction.

PMID- 18317112
TI  - Difficult groin reconstruction using contralateral rectus abdominis myocutaneous
      flap.

PMID- 18317113
TI  - A novel method of rapid nail bed repair using 2-octyl cyanoacrylate (Dermabond).

PMID- 18317114
TI  - The clenched fist syndrome revisited.

PMID- 18317115
TI  - Microvascular transfer of a "lymphatic-bearing" flap in the treatment of
      obstructive lymphedema.

PMID- 18317116
TI  - Biobrane: a versatile tool in the armamentarium of the reconstructive and burns
      surgeon.

PMID- 18317117
TI  - The role of travel guides in the prevention of skin cancer.

PMID- 18317118
TI  - Fillers and biocompatibility: lack of human complement activating capacity.

PMID- 18317119
TI  - Withholding warfarin therapy for atrial fibrillation patients in the
      perioperative period.

PMID- 18317120
TI  - A prospective, randomized, double-blind, controlled trial of continuous local
      anesthetic infusion in cosmetic breast augmentation.
AB  - BACKGROUND: Narcotic pain medications are a significant component of most
      postoperative pain control regimens. Although they are usually effective, they
      produce several untoward side effects and sometimes provide inadequate analgesia.
      The continuous infusion of local anesthetic agents (via pain pump) has been used
      to supplement narcotic analgesics after various surgical procedures. The purpose
      of this study was to examine the effectiveness of the pain pump after cosmetic
      breast augmentation. METHODS: Twenty-five women were enrolled in the study; five
      were eliminated from analysis because of data inadequacy or device problems.
      After bilateral augmentation, the remaining 20 patients received a 4-day
      continuous infusion of bupivacaine in one breast pocket and saline in the other.
      Laterality of bupivacaine infusion was randomized and blinded to both the patient
      and the surgeon. Patients completed a questionnaire on postoperative days 1, 2,
      3, 4, and 7, rating their pain on a scale of 0 to 10, with 10 being worst.
      RESULTS: On postoperative day 1, the mean pain score was 4.7 on the bupivacaine
      side versus 5.4 on the saline side (p = 0.36). On postoperative days 2, 3, 4, and
      7, the mean scores were 4.3 versus 4.6 (p = 0.63), 3.3 versus 3.8 (p = 0.50), 3.4
      versus 3.6 (p = 0.78), and 3.4 versus 3.1 (p = 0.63) for the bupivacaine and
      saline sides, respectively. CONCLUSIONS: The pain pump appears to provide breast
      augmentation patients marginal improvement in pain control, although this
      advantage did not reach statistical significance in this study. The benefit, if
      real, also appears to wane over the first postoperative week.

PMID- 18317121
TI  - Assessment of immediate conservative breast surgery reconstruction: a
      classification system of defects revisited and an algorithm for selecting the
      appropriate technique.
AB  - BACKGROUND: Although various techniques have been used for breast conservation
      surgery reconstruction, there are few studies describing a logical approach to
      reconstruction of these defects. The objectives of this study were to establish a
      classification system for partial breast defects and to develop a reconstructive
      algorithm. METHODS: The authors reviewed a 7-year experience with 209 immediate
      breast conservation surgery reconstructions. Mean follow-up was 31 months. Type I
      defects include tissue resection in smaller breasts (bra size A/B), including
      type IA, which involves minimal defects that do not cause distortion; type IB,
      which involves moderate defects that cause moderate distortion; and type IC,
      which involves large defects that cause significant deformities. Type II includes
      tissue resection in medium-sized breasts with or without ptosis (bra size C), and
      type III includes tissue resection in large breasts with ptosis (bra size D).
      RESULTS: Eighteen percent of patients presented type I, where a lateral
      thoracodorsal flap and a latissimus dorsi flap were performed in 68 percent.
      Forty-five percent presented type II defects, where bilateral mastopexy was
      performed in 52 percent. Thirty-seven percent of patients presented type III
      distortion, where bilateral reduction mammaplasty was performed in 67 percent.
      Thirty-five percent of patients presented complications, and most were minor.
      CONCLUSIONS: An algorithm based on breast size in relation to tumor location and
      extension of resection can be followed to determine the best approach to
      reconstruction. The authors' results have demonstrated that the complications
      were similar to those in other clinical series. Success depends on patient
      selection, coordinated planning with the oncologic surgeon, and careful
      intraoperative management.

PMID- 18317122
TI  - Redesigned gluteal artery perforator flap for breast reconstruction.
AB  - BACKGROUND: The standard elliptical gluteal artery perforator (SE-GAP) flap is an
      alternative to the transverse rectus abdominis myocutaneous flap in patients
      undergoing breast reconstruction. However, many experienced surgeons find use of
      it technically difficult, and the complication rate is high. The author
      investigated whether a redesigned gluteal artery perforator (R-GAP) flap is more
      reliable than the SE-GAP flap for breast reconstruction. METHODS: The author
      retrospectively reviewed the records of 12 patients with 13 reconstructed
      breasts: four underwent unilateral SE-GAP flap reconstruction, one underwent
      bilateral SE-GAP flap reconstruction, and seven underwent unilateral R-GAP flap
      reconstruction. All patients had their information entered prospectively into a
      clinical database and were followed longitudinally. Differences between the
      reconstruction options were assessed using a two-sided Fisher's exact test.
      RESULTS: The complication rate was higher with SE-GAP flaps (67 percent) than
      with the R-GAP flaps (29 percent). Recipient-site complication rates were 50
      percent with SE-GAP and 14 percent with R-GAP flaps; donor-site complication
      rates were 17 percent with SE-GAP and 14 percent with R-GAP flaps. Cosmetic
      outcomes were worse with SE-GAP flaps: there was insufficient volume to achieve
      the desired breast size in 83 percent of SE-GAP versus no R-GAP flap
      reconstructions (p = 0.0047); the reconstructed breast had an irregular contour
      in 67 percent of SE-GAP versus no R-GAP flap reconstructions (p = 0.0210); and a
      major revision of the reconstructed breast was required in 50 percent of SE-GAP
      but no R-GAP flap reconstructions (p = 0.0699). CONCLUSIONS: The R-GAP flap is
      more reliable than the SE-GAP flap and permits successful reconstruction of
      larger breasts. Surgeons should consider incorporating R-GAP flap breast
      reconstruction into their clinical practices.

PMID- 18317123
TI  - Choosing the superomedial pedicle for reduction mammaplasty in gigantomastia.
AB  - BACKGROUND: The optimal reduction technique for the treatment of macromastia
      greater than 1 kg remains controversial. Conventionally, breast amputation and
      free nipple grafting has been used, but this leaves a flat and insensate nipple.
      Anatomical studies have suggested the superomedial technique to be a safe choice
      in these patients. METHODS: A retrospective study analyzing the outcome of
      reduction mammaplasty for macromastia greater than 1 kg using the superomedial
      pedicle technique was performed. Data were collected over a 10-year period from
      1995 to 2005. All reduction mammaplasty patients with resection weights greater
      than 1 kg per breast were included in the study. RESULTS: Sixty-one patients were
      included (122 breasts). The mean age was 29 years. The mean suprasternal notch to
      nipple distance was 35 cm on the left and 35 cm on the right, and the mean nipple
      to inframammary crease distance was 19 cm on the left and 20 cm on the right. The
      Wise keyhole reduction pattern technique was used for all patients. Mean follow
      up was 12 months. The mean resection weight per breast was 1360 g for the left
      breast and 1398 g for the right breast. Fifteen different surgeons performed the
      operations over this period. All patients had viable nipples postoperatively;
      there was partial areola necrosis in eight breasts (6.5 percent), with only minor
      other complications, including T-junction breakdown in 22 breasts (18 percent)
      and dog-ear excisions. CONCLUSIONS: This study has confirmed the superomedial
      pedicle technique to be safe and reliable for resections greater than 1 kg.

PMID- 18317124
TI  - Power-assisted liposuction and the pull-through technique for the treatment of
      gynecomastia.
AB  - BACKGROUND: Gynecomastia is a common condition affecting many adolescent and
      adult males. Surgical techniques utilizing a variety of incisions, excisions,
      suction-assisted lipectomy, ultrasound-assisted liposuction, power-assisted
      liposuction, or some combination of these methods have been used in the treatment
      of gynecomastia. This article describes the authors' method of using power
      assisted liposuction and the pull-through technique to treat gynecomastia.
      METHODS: This technique involves the use of power-assisted liposuction to remove
      fatty breast tissue. The pull-through technique is then performed utilizing
      several instruments to sever the subdermal attachments of fibroglandular breast
      tissue; this tissue is removed through the incision used for liposuction.
      Finally, power-assisted liposuction is performed again to contour the remaining
      breast tissue. A chart review of 99 consecutive patients (197 breasts) treated
      between January of 2003 and November of 2006 was performed. RESULTS: Ninety-six
      patients (192 breasts) were successfully treated using this technique. Power
      assisted liposuction was performed in all cases, and the average volume aspirated
      per breast was 459 ml (range, 25 to 1400 ml). Using the pull-through technique,
      the authors were able to remove between 5 and 70 g of tissue per breast.
      Complications were minimal (1.0 percent of breasts), and no revisions were
      required. CONCLUSIONS: Since January of 2003, the authors have used this
      technique to successfully treat 97 percent of their gynecomastia patients.
      Combining power-assisted liposuction and the pull-through technique has proven to
      be a versatile approach for the treatment of gynecomastia and consistently
      produces a naturally contoured male breast while resulting in a single
      inconspicuous scar.

PMID- 18317125
TI  - Treatment of hydroxyapatite scaffolds with fibronectin and fetal calf serum
      increases osteoblast adhesion and proliferation in vitro.
AB  - BACKGROUND: The use of hydroxyapatite in reconstructive surgery has been hampered
      by the fact that it is very slowly invaded by host tissues, a process that is
      critical to graft incorporation. Implant compatibility may be augmented by
      providing cellular binding sites and by seeding cells before implantation.
      METHODS: Bone-forming cells were seeded onto hydroxyapatite disks, and precoated
      with fibronectin and fetal calf serum or phosphate-buffered saline. Cellular
      adhesion and proliferation was analyzed in vitro. For in vivo studies,
      experimental and control hydroxyapatite disks were seeded with green fluorescent
      protein-expressing cells and implanted into mice. RESULTS: Fibronectin/fetal calf
      serum pretreatment improved cell attachment and cell growth significantly in
      vitro. After 48 hours, experimental disks (n = 5) contained 2.8 times more
      attached cells than controls (p < 0.001), and after 7 days this difference had
      increased further (4.2 times) (p < 0.001). In the in vivo part of the study,
      sections from implants (n = 4) harvested 3 days after implantation demonstrated
      an average of 122 +/- 50 green fluorescent protein-labeled cells/mm in the
      fibronectin/fetal calf serum group compared with 85 +/- 21 cells/mm in the
      phosphate-buffered saline controls. After 10 days, the cells had in general
      decreased in number in both groups, but the relation in cell density was similar
      to the first time point (19 +/- 11 versus 12 +/- 11 cells/mm). CONCLUSION: In
      vitro attachment and proliferation of bone-forming cells on hydroxyapatite is
      significantly increased by pretreatment with fibronectin/fetal calf serum, but
      this difference is less profound and not significant in vivo.

PMID- 18317126
TI  - Radiation-induced craniofacial bone growth inhibition: in vitro cytoprotection in
      the rabbit orbitozygomatic complex periosteum-derived cell culture.
AB  - BACKGROUND: Radiotherapy for the management of head and neck cancer in pediatric
      patients results in severe inhibition of craniofacial bone growth. Previously,
      the infant rabbit orbitozygomatic complex was established as an experimental
      model. Amifostine, a cytoprotective agent, was found effective in preventing
      radiation-induced bone growth inhibition. This study was designed to investigate
      the effects radiation on osteogenic cells from infant rabbit orbitozygomatic
      complex periostea and to assess the effects of cytoprotection in vitro. METHODS:
      Infant New Zealand White rabbits (n = 18) were randomized into three groups and
      received radiation (0, 10, or 15 Gy) to both orbitozygomatic complexes. Cell
      cultures were developed from orbitozygomatic complex periostea, and cell numbers,
      proliferation, alkaline phosphatase, and collagen type I expression and
      mineralization were assessed. Subsequently, rabbits (n = 18) were randomized into
      three groups to receive either radiation at the effective dose, pretreatment with
      amifostine (300 mg/kg, intravenously, 20 minutes before irradiation) with the
      effective radiation dose, or no treatment. Cell cultures were developed and
      tested for proliferation and alkaline phosphatase expression. RESULTS:
      Irradiation resulted in a significant inhibition of cell numbers (p < 0.001) and
      proliferation (p < 0.01) at the 15-Gy dose and no statistically significant
      changes in alkaline phosphatase activity. Collagen type I expression and
      mineralization were also significantly reduced at the 15-Gy dose. Pretreatment
      with amifostine significantly (p < 0.05) enhanced the number of surviving cells.
      CONCLUSIONS: Amifostine is capable of protecting orbitozygomatic complex
      periosteum-derived osteogenic cells from the deleterious effects of radiation.
      This study provides the basis for understanding the cellular mechanisms of
      radiation-induced craniofacial bone growth inhibition and cytoprotection by
      amifostine.

PMID- 18317127
TI  - Three- and four-dimensional computed tomographic angiography and venography for
      the investigation of the vascular anatomy and perfusion of perforator flaps.
AB  - BACKGROUND: Two-dimensional contrast radiography is the current standard for
      investigating the vascular anatomy of surgical flaps. The microvascular anatomy
      of the perforator flap, however, is limited conceptually by representation in two
      dimensions. Static three-dimensional computed tomographic angiography enables
      vascular anatomy to be evaluated in the coronal, axial, and sagittal planes, and
      dynamic four-dimensional computed tomographic angiography allows the vascular
      filling of a perforator flap to be visualized over short time intervals in three
      dimensions. METHODS: An anatomical study was performed using 11 fresh adult
      cadavers acquired through the Willed Body Program at the University of Texas
      Southwestern Medical Center, in Dallas, Texas. Four male and seven female
      cadavers were included in the study. Perforator flaps harvested included the
      following: anterolateral thigh, deep inferior epigastric perforator, superior
      gluteal artery perforator, inferior gluteal artery perforator, thoracodorsal
      artery perforator, anteromedial thigh, and dorsal intercostal artery perforator.
      CONCLUSIONS: Novel techniques for acquiring both static and dynamic three
      dimensional images of macrovascular and microvascular perforator flap anatomy
      using computed tomographic angiography have been described. This methodology has
      also allowed the sequential investigation of adjacent vascular territories. This
      can provide a better understanding of how perforator flaps and the skin are
      perfused and may aid in the future design of new flaps.

PMID- 18317128
TI  - A novel biomimetic material for engineering postsurgical adhesion using the
      injured digital flexor tendon-synovial complex as an in vivo model.
AB  - BACKGROUND: Many surgical procedures are complicated by adhesions. These
      restrictive fibrotic bands form between normally separate gliding tissue layers,
      potentially impairing function. The authors tested the adhesion-modifying effect
      of a novel fibronectin-derived biomimetic biomaterial in a tendon-synovial
      complex injury model. METHODS: The deep flexor tendons of digits 2 and 4 in the
      right forepaw of 15 New Zealand White rabbits were subjected to 5-mm-long partial
      tenotomies. Animals were randomized to receive biomaterial tubes enveloping the
      tendon injuries or left untreated. Digits, amputated at 2 weeks, were randomized
      to mechanical pullout assessments of adhesion strength or to quantitative
      histologic cellularity and immunohistochemical proliferation (Ki67) assessments.
      RESULTS: The mean peak pullout force required to break the adhesions was reduced
      from 7.70 N (n = 6) in untreated digits to 0.31 N (n = 7) in biomaterial-treated
      digits (p = 0.001). The mean structural stiffness of the adhesions was also
      significantly reduced (p = 0.001). Histologically, treated and untreated digits
      demonstrated an equal incidence of adhesions. The treated adhesions were 55
      percent less cellular at their surface than the untreated injured controls (p =
      0.003). Treated tendons were 8 percent more cellular (with equal numbers of
      proliferating cells) at their surface and significantly more cellular within
      their bulk than positive controls (p <or= 0.05). CONCLUSION: This study suggests
      a significant reduction in the restrictive nature of postsurgical adhesions
      following treatment with the antiadhesive biomaterial without compromising tendon
      cellularity.

PMID- 18317129
TI  - An algorithm for total and subtotal facial reconstruction using an expanded
      transposition flap: a 20-year experience.
AB  - BACKGROUND: Reconstruction of major facial soft-tissue deformities and deficits
      is a continuing challenge for surgeons who wish to reliably restore facial
      function and appearance. A primary problem is deficiency of well-matched donor
      skin. Others include the unique characteristics of facial skin, the fine
      anatomical nuances, and the unique functional demands placed on the face making
      reconstruction difficult. The author presents an algorithm developed for total
      and subtotal reconstruction of the face using an expanded shoulder transposition
      flap as a key element. METHODS: Expanded shoulder transposition flaps have been
      used since 1986 for head and neck resurfacing. An algorithm using the expanded
      shoulder transposition flap as a key element was developed for total and subtotal
      resurfacing of the face. The validity of this approach was evaluated by clinical
      results over 20 years. During that time, expanded shoulder transposition flaps
      were used 58 times in 41 patients ranging in age from 2 to 62 years. RESULTS:
      With the expanded shoulder transposition flap as its central component, the
      algorithm proved remarkably reliable and reproducible in resurfacing the
      peripheral facial aesthetic units with the main flap, and the pedicle skin often
      used for grafting the central face with its finer features. The donor site of the
      flap is closed primarily. CONCLUSIONS: This study examines the experience using
      an algorithm developed with the expanded shoulder transposition flap for major
      facial reconstruction. The experience suggests that the algorithm provides
      versatility and reliability; minimizes the donor-site defect; and is well within
      the skill, patience, and courage of most reconstructive surgeons.

PMID- 18317130
TI  - Experience with the gold weight and palpebral spring in the management of
      paralytic lagophthalmos.
AB  - BACKGROUND: The loss of the blink reflex and the ability to close the eye
      actively are disabling functional and aesthetic impairments common to patients
      with facial paralysis. Nonphysiologic (static) management techniques involve
      implantation of devices in the upper eyelid that mechanically aid eye closure.
      The most popular devices are the gold weight and the palpebral spring. The
      authors' experience with these devices is presented. METHODS: Thirty-nine
      patients treated for paralytic lagophthalmos by the senior author (J.K.T.)
      between 1987 and 2002 met the inclusion criteria. Eighteen patients received the
      gold weight and 21 received the palpebral spring. From standardized video
      records, preoperative and postoperative blink scores were calculated. RESULTS:
      Fifty-nine percent of the patients (23 of 39) were female, and the most common
      cause for facial paralysis [35.9 percent (14 of 39)] was extirpation of acoustic
      neuroma and other cerebellopontine lesions. Fifty percent of the gold weight
      cohort was younger than 20 years at the time of surgery, with almost 40 percent
      (seven of 18) younger than 10 years. In the palpebral spring group, 14.3 percent
      (three of 21) were younger than 20 years, with 4.8 percent (one of 21) younger
      than 10 years. The palpebral spring group obtained a larger postoperative mean
      blink score of 34.0 +/- 12.4 percent compared with the gain of 21.4 +/- 14.6
      percent (p = 0.025) by the gold weight group. CONCLUSION: The gold weight and
      palpebral spring are both effective in restoring motion to the paretic upper
      eyelid, but the palpebral spring is more so despite the frequent need for
      revisions.

PMID- 18317131
TI  - A comparative anatomical study of brachioradialis and flexor carpi ulnaris
      muscles: implications for total tongue reconstruction.
AB  - BACKGROUND: Total or subtotal glossectomy following resection of intraoral tumors
      causes significant morbidity. Recent surgical endeavors have focused on the
      creation of a neotongue with both sensory and motor innervation. Although various
      local or regional free flaps have been used for this purpose, the optimal donor
      site remains undecided. The authors compared the neurovascular anatomy of the
      brachioradialis and flexor carpi ulnaris to assess their suitability as donor
      muscles together with overlying skin for functional total or subtotal tongue
      reconstruction. METHODS: Eighty-eight brachioradialis and 80 flexor carpi ulnaris
      muscles were studied, comprising 120 dissected specimens, 18 arterial studies,
      two venous studies, 20 histologic studies, and eight neurovascular studies.
      RESULTS: The dominant vascular pattern of the brachioradialis varied. The major
      pedicle arose from the radial (38 percent), radial recurrent (42 percent), and
      brachial arteries (20 percent). The muscle also lacked a single neurovascular
      pedicle. The vasculature of the flexor carpi ulnaris was consistent. The ulnar
      artery supplied the dominant pedicle in 86 percent of cases. The entry point of
      motor innervation is near that of the vascular pedicles. A minor distal nerve
      accompanied the main vascular pedicle in 65 percent of cases. The overlying skin
      was supplied by musculocutaneous perforators. The lower lateral cutaneous nerve
      of the arm supplied the skin over the brachioradialis, and the medial cutaneous
      nerves of the arm and forearm provided sensation over the flexor carpi ulnaris.
      CONCLUSION: The authors delineated the anatomical advantages of the flexor carpi
      ulnaris over the brachioradialis for total or subtotal tongue reconstruction.

PMID- 18317132
TI  - Vacuum-assisted closure for defects of the abdominal wall.
AB  - BACKGROUND: Reconstruction of the abdominal wall poses a problem common to many
      surgical specialties. Abdominal wall defects may be caused by trauma and/or prior
      surgery, with dehiscence or infection. Several options to repair the structural
      integrity of the abdominal wall exist, including primary closure, flaps, mesh,
      and skin grafts. Complications of these procedures include recurrent infection of
      the abdominal wall, infection of mesh, dehiscence, flap death, and poor skin
      graft take. Risk factors predisposing to these complications include tissue
      edema, preoperative tissue infection, and patient debilitation, with poor wound
      healing potential. Ideally, reconstruction should be performed on a nonedematous,
      clean tissue bed with bacterial levels less than 10 bacteria/cm in a well
      nourished patient. METHODS: Vacuum-assisted closure was used in a series of
      patients in an attempt to prepare the abdominal wall for reconstruction and
      reduce the risk of complications. Charts were reviewed for 100 patients who
      underwent abdominal wall reconstruction after vacuum-assisted closure therapy.
      Their wound cause, reconstruction technique, complications, and number of days on
      the vacuum-assisted closure device are reported. RESULTS: The ability of vacuum
      assisted closure to reduce edema, increase blood flow, potentially decrease
      bacterial colonization, and reduce wound size greatly facilitated abdominal wall
      reconstruction. The vacuum-assisted closure device served as a temporary dressing
      with which to control dehiscence and to maintain abdominal wall integrity when
      bowel wall edema prevented abdominal closure. CONCLUSION: Vacuum-assisted closure
      therapy frequently shortened time to abdominal wall reconstruction and simplified
      the method of reconstruction.

PMID- 18317133
TI  - Different types of suprafascial courses in thoracodorsal artery skin perforators.
AB  - BACKGROUND: The thoracodorsal artery perforator flap is a versatile flap for
      resurfacing soft-tissue defects. However, it is too bulky for resurfacing shallow
      defects. The authors used preoperative color Doppler sonography to identify the
      suprafascial courses of skin perforators to facilitate the design and thinning
      procedures of thoracodorsal artery perforator flaps. METHODS: Thin thoracodorsal
      artery perforator flaps were designed in 29 patients. Preoperative color Doppler
      sonography was used to identify the penetrating points and suprafascial courses
      of skin perforators. According to the different orientations of suprafascial
      courses, skin perforators could be classified into three types. The designs and
      thinning procedures of flaps relied on the findings of preoperative color Doppler
      sonography. RESULTS: Fifty-eight ideal perforators were marked on the 29
      patients. Intraoperative dissections proved that 55 perforators were
      thoracodorsal artery skin perforators, and three perforators were intercostal
      artery perforators. In one patient, no skin perforator derived from the
      descending branch of the thoracodorsal artery was found during intraoperative
      dissection (3.4 percent). Suprafascial courses could be demonstrated by
      preoperative color Doppler sonography in 54 of the 55 thoracodorsal artery skin
      perforators. Nineteen were type 1 perforators (35.2 percent), 26 were type 2
      perforators (48.1 percent), and nine were type 3 perforators (16.7 percent).
      Complications were encountered in six patients (20.7 percent), all of whom
      recovered well. CONCLUSIONS: The suprafascial courses of skin perforators
      facilitate the design and thinning procedures of thoracodorsal artery perforator
      flaps. They improve the survivability of flaps and make thinning procedures more
      secure and efficient.

PMID- 18317134
TI  - Chest-wall contouring surgery in female-to-male transsexuals: a new algorithm.
AB  - BACKGROUND: In female-to-male transsexuals, the first surgical procedure in their
      reassignment surgery consists of the subcutaneous mastectomy. The goals of
      subcutaneous mastectomy are removal of breast tissue, removal of excess skin,
      reduction and proper positioning of the nipple and areola, and ideally,
      minimization of chest-wall scars. The authors present the largest series to date
      of female-to-male transsexuals who have undergone subcutaneous mastectomy.
      METHODS: A total of 184 subcutaneous mastectomies were performed in 92 female-to
      male transsexuals, using the following five techniques: semicircular,
      transareolar, concentric circular, extended concentric circular, and free nipple
      graft. The technique used depended on the breast size and envelope, the aspect
      and position of the nipple-areola complex, and the skin elasticity. To best meet
      the goals of creating a normal male thorax, the authors have developed an
      algorithm to aid in choosing the appropriate procedure. RESULTS: The overall
      postoperative complication rate was 12.5 percent (23 of 184 subcutaneous
      mastectomies), and in eight of these cases (4.3 percent), an additional operative
      intervention was required because of hematoma, infection, and/or wound
      dehiscence. Despite this low complication rate, additional procedures for
      improving aesthetic results were performed on 59 breasts (32.1 percent). The
      semicircular and concentric circular techniques produced the highest rating of
      the overall result by patient and surgeon, whereas the extended concentric
      circular technique produced the lowest rating. CONCLUSIONS: Skin excess and skin
      elasticity are the key factors in choosing the appropriate technique for
      subcutaneous mastectomy, which is reflected in the algorithm. Although the
      complication rate is low and patient satisfaction is high, secondary aesthetic
      corrections are often indicated.

PMID- 18317135
TI  - Wound therapy by marrow mesenchymal cell transplantation.
AB  - BACKGROUND: Marrow mesenchymal cells are useful in regenerative medicine because
      they contain stem cells, but there have been few reports of clinical
      applications. The authors developed a new wound treatment technique by improving
      marrow mesenchymal cell culture methods and placing cultured cells in an
      artificial skin material. This new treatment was useful for tissue regeneration
      in 20 patients with skin wounds. METHODS: Marrow mesenchymal cells from a 46-year
      old man were cultured and placed in artificial dermis made of collagen sponge.
      This composite graft was implanted subcutaneously into the back of a nude mouse
      and removed 10 days later; immunohistological analysis confirmed regeneration of
      subcutaneous tissue using human marrow mesenchymal cells. Next, in 20 patients
      (nine men and 11 women; average age, 64.8 years; range, 22 to 91 years) with
      intractable dermatopathies, 10 to 20 ml of bone marrow fluid was aspirated from
      the ilium and cultured in medium containing either fetal calf or autologous
      serum. The resulting cultured cells were placed in artificial dermis made of
      collagen sponge, and this composite graft was used to treat skin wounds. RESULTS:
      The wound mostly healed in 18 of the 20 patients; the remaining two patients died
      of causes unrelated to transplantation. In all patients, autologous marrow
      mesenchymal cell transplantation was shown to be therapeutically effective.
      CONCLUSIONS: In skin regeneration therapy using a marrow mesenchymal
      cell/artificial dermis composite graft, skin regeneration is possible with bone
      marrow aspiration, a minimally invasive procedure. Compared with existing skin
      grafting techniques, the present technique is practical and much less invasive.

PMID- 18317136
TI  - Therapeutic results of sciatic nerve repair in Iran-Iraq war casualties.
AB  - BACKGROUND: The sciatic nerve is composed of two independent divisions: tibial
      and peroneal. The results of the repair of these two nerves are not identical.
      This retrospective study was carried out with the aim of evaluating the results
      of different therapeutic procedures for sciatic nerve injuries and conducting a
      comparative evaluation of peroneal and tibial nerve recovery. METHODS: A total of
      648 Iranian casualties of the 1980 to 1988 Iran-Iraq war with sciatic nerve
      injury were treated with nerve grafting, direct end-to-end coaptation, and
      neurolysis. Patients were subdivided according to nerve injury site into three
      groups of upper, middle, and lower thirds of the thigh, and followed from 5 to 12
      years. RESULTS: In 77.8 percent of patients, the tibial nerve was injured, and in
      88.9 percent, the common peroneal nerve was injured. Protective sensation
      recovery of the sole was evaluated as good in 69.1 percent of those with upper
      third injuries, 74.4 percent of those with middle third injuries, and 89.3
      percent of those with lower third repairs (p < 0.0001), with an overall success
      rate of 73.4 percent. The overall motor recovery success rate for the three
      techniques was 86.3 percent for the tibial nerve and 38.9 percent for the common
      peroneal nerve. CONCLUSIONS: Results of sciatic nerve injury treatment in this
      group of war casualties were generally satisfactory. Tibial nerve injury repair
      in the upper thigh has a higher priority than the peroneal nerve. Motor deficits
      of the common peroneal nerve can be overcome by tendon transfer or orthopedic
      devices.

PMID- 18317137
TI  - Pedicled and free radial forearm flaps for reconstruction of the elbow, wrist,
      and hand.
AB  - BACKGROUND: A single surgeon's experience with 67 pedicled and free radial
      forearm flaps for reconstruction of the elbow, wrist, and hand was analyzed
      retrospectively. METHODS: Fifty-seven pedicled (43 reverse and 14 antegrade flow)
      and 10 free radial forearm flaps were performed in 66 patients, including seven
      fascial flaps and one osteocutaneous flap. Indications involved soft-tissue
      coverage of the elbow (n = 11), dorsal wrist and hand (n = 24), palmar wrist and
      hand (n = 12), and thumb amputations (n = 5); after release of thumb-index finger
      web space contractures (n = 6) and radioulnar synostosis (n = 2); before toe-to
      thumb transfers (n = 3); for reconstruction following tumor excision (n = 13);
      and for wrapping of the median, ulnar, and radial nerves for traction neuritis (n
      = 5). RESULTS: Primary healing of the soft-tissue defect of the elbow, wrist, and
      hand was successful in 95 percent of patients. There was one flap dehiscence,
      partial loss of two reverse radial forearm flaps, and complete loss of one free
      radial forearm flap. Eleven donor sites were closed primarily and 56 were covered
      with a split-thickness skin graft. No patients complained specifically of cold
      intolerance of the hand or dysesthesias in the superficial radial nerve or
      lateral antebrachial nerve distribution. CONCLUSIONS: This is the largest
      reported series of radial forearm flaps for reconstruction of the upper
      extremity. The authors believe the antegrade pedicled radial forearm flap is the
      optimal flap for coverage of defects around the elbow, and the reverse radial
      forearm flap is the optimal choice for coverage of moderate-sized defects of the
      wrist and hand.

PMID- 18317138
TI  - Partial second toe pulp free flap for fingertip reconstruction.
AB  - BACKGROUND: The authors present their clinical experience and surgical methods of
      fingertip coverage using a short-pedicle partial medial second toe pulp free
      flap. The surgical steps for reducing surgical time and donor-site morbidity are
      described. METHODS: Between April of 1999 and September of 2006, 929 partial
      second toe pulp free flaps were performed in 854 patients. The indications for
      this flap were preservation of digital length to cover exposed bone and
      replacement of skin over unstable fingertip scars. A total of 156 patients were
      assessed more than 1 year postoperatively with the two-point discrimination test.
      RESULTS: The mean patient age was 34 years (range, 20 months to 72 years); 747 of
      854 were male. The overall survival rate was 99.7 percent. Fifty-seven patients
      had two fingertip defects covered with bilateral second toe pulp flaps and nine
      had three defects covered with bilateral second toe pulp flaps and a third toe
      pulp flap. Donor-site complications occurred in 59 cases (hematoma, n = 39; wound
      separation, n = 20). No gait disturbance or painful toes were observed at the
      donor site. Static two-point discrimination averaged 8 mm (range, 4 to 15 mm). A
      total of 264 patients required additional surgical procedures, including skin
      grafting at the recipient site (n = 154) and secondary flap revision (n = 110).
      CONCLUSIONS: The shorter pedicle and smaller flap can reduce the surgical time
      and morbidity associated with this procedure. This flap is the authors' first
      line of treatment for covering fingertip wounds by transferring similar pulp
      tissue from the toe to the finger.

PMID- 18317139
TI  - The role of peripheral nerve surgery in the treatment of chronic pain associated
      with amputation stumps.
AB  - BACKGROUND: Debilitating pain following amputation surgery can seriously affect
      the long-term success of the operation and the patient's quality of life. Often,
      such patients are unable to ambulate because of pain when using a prosthesis;
      become grouped in the chronic pain category; and are treated with high-dose
      narcotics, antidepressants, or other methods to treat symptoms that may provide
      little or no relief. Little attention has been given to the role of peripheral
      nerve surgery as an early treatment option. METHODS: A retrospective review of 21
      consecutive amputees with chronic stump pain was performed. The surgical
      technique included removal of the neuroma with implantation of the proximal nerve
      ending into adjacent muscle. In addition to the surgical outcome, other variables
      evaluated included resolution or optimal improvement in pain and spasms, change
      in quality of life, and ambulation status. RESULTS: The mean duration of stump
      pain before surgery was 7.28 months (range, 5 to 18 months). After surgery, there
      were statistically significant changes with pain and spasms, quality-of-life, and
      ambulation status. The mean follow-up was 22.8 months, and there was no
      recurrence of neuroma. CONCLUSIONS: Peripheral nerve surgery plays a significant
      role in the treatment of chronic pain associated with amputation stumps. After
      conservative treatment methods have been exhausted, a treatment algorithm for
      peripheral nerve surgery is successful in improving or resolving chronic pain and
      the quality-of-life issues associated with amputation patients.

PMID- 18317141
TI  - The natural history of patients treated for FGFR3-associated (Muenke-type)
      craniosynostosis.
AB  - BACKGROUND: Muenke-type craniosynostosis is defined as fibroblast growth factor
      receptor 3 (FGFR3)-associated coronal craniosynostosis with or without mental
      retardation. With complementary genetic information, more precise diagnosis and
      long-term functional outcome of cranial vault remodeling in affected patients can
      be studied, and additional distinct features of Muenke syndrome can now be
      investigated. This study was undertaken to assess craniofacial growth and long
      term functional outcome in patients with Muenke-type craniosynostosis. METHODS: A
      chart review of all FGFR3 patients at The Children's Hospital of Philadelphia who
      had undergone cranial vault remodeling for unicoronal or bicoronal synostosis (n
      = 16) was performed. Need for reoperation, midface surgery, and functional
      corrections were assessed. Audiology and orthodontic records were reviewed.
      RESULTS: All patients underwent cranial remodeling during infancy. Repeated
      intracranial surgery was performed or is currently scheduled for aesthetic
      reasons only (n = 7). Sexual dimorphism with male preponderance in FGFR3
      unicoronal synostosis was detected. Despite dental crowding amenable to palatal
      expansion in patients with bicoronal synostosis, significant midface hypoplasia
      was not observed. Sensorineural hearing loss with a distinctive pattern was
      present in all patients who had undergone audiology testing. CONCLUSIONS:
      Patients with FGFR3-associated craniosynostosis demonstrate a sexual dimorphism,
      with a male preponderance for unicoronal synostosis. A secondary major
      intracranial procedure is required for recurrent supraorbital retrusion in at
      least 43 percent of patients. A secondary or tertiary extracranial forehead
      contouring procedure should be anticipated in nearly all patients. No patient
      required any midface correctional procedure. These patients demonstrate
      characteristic bilateral, symmetric, low- to mid-frequency sensorineural hearing
      loss.

PMID- 18317142
TI  - Choice of incision for primary repair of unilateral complete cleft lip: a
      comparative study of outcomes in 796 patients.
AB  - BACKGROUND: No one technique of cleft lip repair consistently produces ideal
      aesthetic and functional results. This study was carried out in a developing,
      high-volume center. It compares outcomes attained using two different designs of
      skin incision used for primary closure of unilateral complete cleft lip and
      sought to identify the most appropriate technique for clefts of varying
      morphology. METHODS: Seven hundred ninety-six patients were entered into the
      study. In each group of slightly less than 400 patients, either a modified
      Millard or Pfeifer wavy line incision was used, both in conjunction with
      functional repair of the underlying tissues as described by Delaire. Soft-tissue
      measurements of the lip and nose were recorded preoperatively. Analysis was based
      on postoperative assessment of the white roll, vermilion border, scar, Cupid's
      bow, lip length, and nostril symmetry and appearance of the alar dome and base.
      RESULTS: Comparison of the two cohorts using Pearson chi-square testing for
      association and linear trend found a Millard incision gave significantly better
      results for vermilion match, whereas the Pfeifer method led to a better
      postoperative lip length. Preconceptions that one particular technique was better
      suited to certain preoperative cleft anatomical forms were not proven
      statistically. CONCLUSIONS: Certain preoperative anatomical features may lead the
      surgeon to choose one particular incision pattern in preference to another, but
      in this study, it was found that one technique was essentially as good as the
      other. This suggests that the technique for closure of the underlying tissues is
      probably of more importance.

PMID- 18317143
TI  - Comparison of a modifiable cranial cup versus repositioning and cervical
      stretching for the early correction of deformational posterior plagiocephaly.
AB  - BACKGROUND: Deformational occipital flattening is the most common cause of
      abnormal head shape. Current treatment calls for repositioning and cervical
      stretching in infants younger than 5 months. The authors assessed the
      effectiveness of a modifiable cranial cup compared to repositioning and cervical
      stretching to correct early deformational plagiocephaly. METHODS: This
      nonrandomized, prospective clinical trial used historical controls. The treatment
      and control groups consisted of infants, younger than 4 months, referred for
      deformational posterior plagiocephaly. The control children were managed by
      repositioning and cervical stretching exercises. An adjustable concave cranial
      cup was used in the treated group. Infants were examined at the initial and final
      visits by a single examiner. Calvarial asymmetry was measured using a large
      cranial caliper. Active head rotation and degree of rotational asymmetry were
      estimated to the nearest 10 degrees. RESULTS: There were no statistically
      significant differences between the control (n = 23) and treatment groups (n =
      24) with respect to gestational age at birth, age at initial visit, initial head
      rotational asymmetry, initial transcranial difference, final head rotational
      asymmetry, and age at final evaluation. Mean time between initial and final
      evaluation was 56.3 days for the treatment group and 61.6 days for the control
      group. The mean transcranial difference decreased from 11.2 to 3.5 mm in the
      treatment group, and from 9.0 to 8.0 mm in the control group (p = 0.000).
      CONCLUSION: The cranial cup, a modifiable concave resting surface, is
      significantly more effective than repositioning and physical therapy for
      correcting early deformational plagiocephaly.

PMID- 18317144
TI  - Gillies elevation and percutaneous Kirschner wire fixation in the treatment of
      simple zygoma fractures: long-term quantitative outcomes.
AB  - BACKGROUND: The objective of zygoma fracture repair is to restore preinjury
      function and appearance. The optimal surgical technique represents a balance
      between accurate fracture reduction and soft-tissue morbidity. METHODS: Fifty
      patients were eligible for review after treatment for isolated simple zygoma
      fractures using a combination of Gillies elevation and percutaneous Kirschner
      wire fixation between 1992 and 2003. Fourteen patients were available for
      examination at a mean follow-up of 8.7 years. Quantifiable parameters, including
      orbitozygomatic complex position, ocular globe projection, and infraorbital nerve
      function, were measured. All patients underwent qualitative assessment by
      independent, blinded observers. Negative soft-tissue sequelae were recorded.
      RESULTS: The mean differences between injured and uninjured sides of the face for
      malar eminence projection, height, and lateral position were 2.5, 2.7, and 2.3
      mm, respectively. The mean difference in ocular globe projection was 1.23 mm.
      When these results were compared with those previously published for open
      reduction and internal fixation, no statistically significant difference was
      noted. The qualitative observers were able to identify the affected side 12
      percent of the time. Other than a small punctate scar noted in one patient at the
      Kirschner wire insertion site, no other negative cutaneous or eyelid sequelae
      were noted. CONCLUSIONS: This study objectively shows that Gillies elevation
      combined with percutaneous Kirschner wire fixation provides facial contour
      restoration that is not significantly different from that of open reduction and
      internal fixation, with less soft-tissue morbidity. The technique is safe, easy
      to learn, and easy to perform, and should be considered in cases of isolated
      simple zygoma fractures.

PMID- 18317145
TI  - Primary simultaneous lip and nose repair in the unilateral cleft lip and palate.
AB  - BACKGROUND: "Do not touch the nose in primary repair of the unilateral cleft lip
      and palate!" In the past, this dogmatic attitude caused functional and aesthetic
      (psychological) problems for the child until secondary corrections during
      adolescence were performed. In the 1950s, surgeons started to correct at least a
      few features of the nasal deformity and to develop radically corrective measures.
      Since 1970, a new and very comprehensive concept of correction has been used at
      the authors' department of plastic and reconstructive surgery. METHODS: Methods
      of primary nasal repair by various surgeons are presented chronologically. The
      main features of the authors' strategy are special incision lines, extensive
      mobilization of all dislocated structures, straightening of the deviated septum,
      correction of the deformed ala and nasal tip, induction of bone growth in
      hypoplastic areas under the alar base and along the piriform aperture, and a
      special suture technique of the orbicularis muscle to form a better philtrum.
      RESULTS: Improvement of the aesthetic and functional results can be achieved with
      this type of nasal repair. Since 1970, approximately 500 patients have been
      operated on with this method at the authors' hospital and elsewhere, with 80
      percent showing satisfactory results and 20 percent revealing deficiencies.
      Severe nasal deformities, which were common when no primary repair was applied,
      were not observed. This observation period provides evidence that no growth
      retardation occurs. CONCLUSIONS: Because of the good results of this method and
      the lack of growth retardation, this approach is to be recommended. It also
      benefits children in underdeveloped countries, where frequent surgery is not
      possible.

PMID- 18317146
TI  - Craniofacial dysmorphology of Carpenter syndrome: lessons from three affected
      siblings.
AB  - BACKGROUND: Carpenter syndrome, or acrocephalopolysyndactyly type II, is a
      disorder associated with an autosomal recessive pattern of inheritance. Because
      of its rarity, limited insight into the anomalies associated with this syndrome
      exist and little long-term follow-up of affected patients is available. METHODS:
      This study is a retrospective review of the clinical history, medical imaging,
      and therapeutic interventions for three full siblings with Carpenter syndrome
      over an 18-year period. The medical records were abstracted for kindred analysis,
      gestational and delivery history, health issues related to Carpenter syndrome,
      and therapeutic interventions, including indications for, age at, and outcome of.
      RESULTS: All three children had craniosynostosis, acral deformities, and other
      associated anomalies. The pattern of craniosynostosis, at birth, varied among the
      three siblings: one had fusion of the metopic and sagittal sutures and the other
      two had bilateral coronal, metopic, and anterior sagittal synostoses. All three
      siblings demonstrated marked absence or underdevelopment of the anterior cranial
      fossa and bulging of the middle cranial fossa. There was no correlation between
      the degree of craniofacial dysmorphology and brain dysmorphology in any of the
      three individuals. Computed tomographic scan data of osseous and brain anatomy
      and clinical photographs of treatment outcomes are provided to demonstrate the
      long-term craniofacial development and growth in treated individuals with
      Carpenter syndrome. CONCLUSIONS: The diverse anatomical variation seen in these
      three individuals supports the notion of marked phenotypic variability within
      this disorder. This spectrum of information should aid members of craniofacial
      teams in appreciating this variability and thereby facilitating the diagnosis and
      management of individuals with Carpenter syndrome.

PMID- 18317147
TI  - Full-face carbon dioxide laser resurfacing: a 10-year follow-up descriptive
      study.
AB  - BACKGROUND: The purposes of this study were to retrospectively compare the 1-, 5
      , and 10-year cosmetic outcomes of full-face carbon dioxide laser resurfacing
      using the SilkTouch technology, and analyze its advantages, disadvantages, and
      long-term results. METHODS: Photographic results of full-face carbon dioxide
      laser resurfacing were evaluated after 1, 5, and 10 years. Statistical analysis
      considered surgeon and patient satisfaction based on a predetermined cosmetic
      visual analogue scale. Patients and two plastic surgeons unfamiliar with the
      cases evaluated objective postresurfacing results using Beausang's grading system
      and a modified wrinkle assessment scale. RESULTS: One hundred fifty-nine patients
      were treated and 46 patients completed 1-, 5-, and 10-year follow-up. Combined
      aesthetic procedures to the full-face carbon dioxide resurfacing were
      transcutaneous upper lid/lower lid transconjunctival blepharoplasty and
      endoscopic brow lifts in 15 patients. After 1 year, some relapse occurred, but
      the overall aesthetic result remained very good. At 5 and 10 years, respectively,
      32 and 20 percent of the sample maintained good-quality skin texture; 22 and 19
      percent achieved correction of skin pigmentation without scars; and 88 and 98
      percent needed correction of recurrent rhytides, jowling, and redundant skin.
      Permanent hypopigmentation was found in four cases (8.7 percent). CONCLUSIONS:
      The authors' early experience with the carbon dioxide laser was excellent, but
      after 1 year, they noticed lines of demarcation between treated and nontreated
      skin or persistent erythema. After 5 and 10 years, advantages were maintenance of
      good skin texture, ablation of fine wrinkles, and long-term correction of skin
      pigmentation. Disadvantages included permanent hypopigmentation of the mandible
      neck junction, telangiectasia, and possible accentuation of skin redundancy.

PMID- 18317148
TI  - The orbicularis retaining ligament of the medial orbit: closing the circle.
AB  - BACKGROUND: There exists some ambiguity regarding the exact anatomical limits of
      the orbicularis retaining ligament, particularly its medial boundary in both the
      superior and inferior orbits. Precise understanding of this anatomy is necessary
      during periorbital rejuvenation. METHODS: Sixteen fresh hemifacial cadaver
      dissections were performed in the anatomy laboratory to evaluate the anatomy of
      the orbicularis retaining ligament. Dissection was assisted by magnification with
      loupes and the operating microscope. RESULTS: A ligamentous system was found that
      arises from the inferior and superior orbital rim that is truly periorbital. This
      ligament spans the entire circumference of the orbit from the medial to the
      lateral canthus. There exists a fusion line between the orbital septum and the
      orbicularis retaining ligament in the superior orbit, indistinguishable from the
      arcus marginalis of the inferior orbital rim. Laterally, the orbicularis
      retaining ligament contributes to the lateral canthal ligament, consistent with
      previous studies. No contribution to the medial canthus was identified in this
      study. CONCLUSIONS: The orbicularis retaining ligament is a true, circumferential
      "periorbital" structure. This ligament may serve two purposes: (1) to act as a
      fixation point for the orbicularis muscle of the upper and lower eyelids and (2)
      to protect the ocular globe. With techniques of periorbital injection with
      fillers and botulinum toxin becoming ever more popular, understanding the
      orbicularis retaining ligament's function as a partitioning membrane is mandatory
      for avoiding ocular complications. As a support structure, examples are shown of
      how manipulation of this ligament may benefit canthopexy, septal reset, and brow
      lift procedures as described by Hoxworth.

PMID- 18317149
TI  - Periorbital aging and ethnic considerations: a focus on the lateral canthal
      complex.
AB  - BACKGROUND: There is a general perception that skin from various ethnic groups
      possesses different properties that may affect barrier function, responsiveness
      to topical agents, sebum production, chemical sensitivities, and aging changes.
      The first noticeable signs of facial aging are frequently localized to the upper
      face, brow, and eyes. The authors postulate that a greater relative descent of
      the lateral canthal complex in African Americans contributes to periorbital aging
      more so than in Caucasians. METHODS: The photographic archives of the senior
      plastic surgeon (J.W.F.) were reviewed. Two hundred ninety-six cases met
      inclusion criteria. Lateral canthal angles were measured, and the angle assigned
      to each patient was an average of the right and left lateral canthal angles.
      RESULTS: Statistically significant intrarace differences were found for the
      lateral canthal angle. The median lateral canthal angle for African American
      patients decreased from 3.00 degrees for those aged 45 years or younger to 1.15
      degrees for African American patients older than 45 years (p = 0.03). The median
      lateral canthal angle for Caucasian patients decreased from 2.30 degrees for
      those aged 45 years or younger to 1.30 degrees for Caucasian patients older than
      45 years (p = 0.00). When the data were age-matched, with 25 subjects in each
      group, the differences increased. CONCLUSIONS: In comparing young and aged
      cohorts, African American women demonstrate a more dramatic attenuation of the
      lateral canthal complex than their Caucasian counterparts. It appears that the
      lateral canthal complex has been underappreciated, and it is a vital component to
      periorbital rejuvenation.

PMID- 18317150
TI  - Nonsurgical treatment of cicatricial ectropion with hyaluronic acid filler.
AB  - BACKGROUND: Cicatricial lower eyelid ectropion is caused by a shortening of the
      anterior lamella, with resultant eversion of the eyelid away from the globe.
      Treatment is typically surgical; however, the author hypothesized that a
      nonsurgical injection of hyaluronic acid filler could stretch the tethered skin
      and act as a tissue expander to correct the lid. METHODS: Fifteen patients with
      lower eyelid cicatricial ectropion were injected with a hyaluronic acid filler
      below the surface of the affected eyelid skin. The patients were followed
      prospectively for over 1 year for outcomes and complications. RESULTS: All
      patients achieved immediate and dramatic correction of their ectropion with a
      single injection. Eleven patients (73 percent) had complete correction lasting
      more than 1 year and four had partial correction. No major complications were
      observed; however, temporary bruising and a Tyndall effect was evident in a
      majority of patients. CONCLUSIONS: Hyaluronic acid filler injections can
      successfully treat cicatricial ectropion by expanding the tethered anterior
      lamella of the skin. This provides an effective alternative to surgical
      correction of the lid. The treatment is quick, safe, and easy to learn.

PMID- 18317151
TI  - Correction of cocaine-related nasal defects.
AB  - BACKGROUND: Cocaine abuse causes nasal defects ranging from minor septal
      perforation to loss of dorsal support, potentially leading to collapse of the
      entire nose. The authors review the defects caused by frequent insufflation of
      cocaine, outline representative internal and external nasal deformities, and
      detail the surgical methods available to correct these deformities. METHODS: The
      patient must be cocaine-free for several years and committed to remaining free of
      cocaine use permanently. Next, a clear definition of the existing deformity and
      precise plan of surgical correction should be established. Surgical correction
      involves adequate dissection of the soft tissues and cephalic release and caudal
      advancement of the nasal lining, with a complete and waterproof separation of the
      nasal cavity from the external reconstructive site. Using costal cartilage, a
      tongue-and-groove technique is used to elongate the nasal frame. Kirschner wires
      may be used for costal cartilage graft fixation; avoiding penetration of the
      nasal cavity is critical. Maxillary defects are restored with cartilage and bone
      grafts. To address notching of the alae, V-to-Y caudal advancement flaps of the
      nasal lining and alar rim grafts are used. Tip projection and definition are
      restored with a columella strut with or without a tip graft. RESULTS: The
      surgical outcome is gratifying and does not necessarily require external skin or
      nasal lining graft, or local or regional flaps. Reconstruction of massive septal
      perforation is unnecessary, as the nasal form can be restored without repair of
      this defect. The key to success is avoiding postoperative infection. CONCLUSION:
      Correction of cocaine-related internal and subsequent external nasal defects is
      extremely challenging and requires a clear understanding of the patient's
      psychology and nasal abnormality.

PMID- 18317152
TI  - Upper lip augmentation: palmaris longus tendon as an autologous filler.
AB  - BACKGROUND: Lip augmentation is used to enhance a thin upper lip or correct lip
      deficiencies. The palmaris longus tendon, an accessory tendon of the wrist, has
      been used successfully for upper extremity reconstruction and was used in this
      case series for upper lip augmentation. METHODS: Patients underwent upper lip
      augmentation using palmaris longus tendon grafts at the University of California,
      Los Angeles from 1998 to 2005 (n = 38). Vertical lip height, lateral lip
      projection, and dynamic smile length were measured preoperatively, at 6 weeks,
      and at 1-year follow-up, and complications, lip mobility, and physician/patient
      outcome surveys were recorded. RESULTS: Palmaris graft lip augmentation was
      performed for cosmetic (n = 21) and reconstructive (n = 17) indications. There
      were two infections and two graft exposures, with no long-term sequelae. The
      vertical height of the upper lip had a mean increase of 204 percent and a mean
      relapse of 9 percent (change from postoperative period to follow-up). Lateral
      projection of the upper lip showed a mean increase of 180 percent and a relapse
      rate of 7 percent. Dynamic lip mobility had a mean grade of 4.7 of 5 at 1 year,
      and the postoperative smile length was close to the preoperative length (mean
      postoperative length was 96 percent of preoperative length). One patient
      developed a stiff upper lip and required reoperation and therapy for a good final
      outcome. CONCLUSION: The authors' case series shows that the palmaris longus
      tendon provides a reliable option for soft-tissue upper lip augmentation, with
      improved vertical height and lateral projection and maintenance of lip mobility.

PMID- 18317153
TI  - Influences of centrifugation on cells and tissues in liposuction aspirates:
      optimized centrifugation for lipotransfer and cell isolation.
AB  - BACKGROUND: Although injective autologous fat transplantation is one of the most
      attractive options for soft-tissue augmentation, problems such as
      unpredictability and fibrosis resulting from fat necrosis limit its universal
      acceptance. Centrifugation is one of most common methods for overcoming these
      difficulties. This study was performed to investigate quantitatively the effects
      of centrifugation on liposuction aspirates to optimize centrifugal conditions for
      fat transplantation and isolation of adipose-derived stem cells. METHODS:
      Liposuction aspirates, obtained from eight healthy female donors, were either not
      centrifuged or centrifuged at 400, 700, 1200, 3000, or 4200 g for 3 minutes. The
      volumes of the oil, adipose, and fluid portions and numbers of blood cells and
      adipose-derived cells in each portion were examined. The processed adipose
      tissues (1 ml) were injected into athymic mice, and grafts were harvested and
      weighed at 4 weeks. Morphologic alterations were observed using light and
      scanning electron microscopy. RESULTS: Centrifugation concentrated adipose
      tissues and adipose-derived stem cells in the adipose portion and partly removed
      red blood cells from the adipose portion. Centrifugation at more than 3000 g
      significantly damaged adipose-derived stem cells. Centrifugation enhanced graft
      take per 1 ml centrifuged adipose but reduced calculated graft take per 1 ml
      adipose before centrifugation. CONCLUSIONS: Excessive centrifugation can destroy
      adipocytes and adipose-derived stem cells, but appropriate centrifugation
      concentrates them, resulting in enhanced graft take. The authors tentatively
      recommend 1200 g as an optimized centrifugal force for obtaining good short- and
      long-term results in adipose transplantation.

PMID- 18317155
TI  - Applying to plastic surgery residency: factors associated with medical student
      career choice.
AB  - BACKGROUND: Applications to plastic surgery residency increased 34 percent from
      2002 to 2005, despite decreasing applications to other surgical subspecialties.
      During this period, medical education, reimbursement, work hours, and media
      coverage have changed. METHODS: To determine factors responsible for rising
      applications to plastic surgery residencies, medical student applicants to
      plastic surgery residencies for 2005 were surveyed. Applicants recorded exposure
      to plastic surgery during medical school and graded the influence of personality,
      lifestyle, income potential, and media coverage on their decision to choose
      plastic surgery training. To further study the effects of plastic surgery
      exposure on career choice, the percentage of graduating students applying to
      plastic surgery residency was compared between medical schools with and without
      plastic surgery training programs. RESULTS: Medical schools that provided greater
      exposure to plastic surgery and schools with plastic surgery training programs
      had a higher percentage of graduates applying to plastic surgery residency (p <
      0.001). Applicants rated compatibility with the personality of plastic surgeons
      as a significant factor in their career choice. Lifestyle and income potential
      were moderately important, whereas media coverage minimally affected career
      decision. Applicants typically decided on a plastic surgical career during the
      third year of medical school. CONCLUSIONS: Medical student exposure to plastic
      surgery is the most influential factor in a student's decision to pursue a career
      in plastic surgery. To continue the increasing applicant trend toward plastic
      surgery, plastic surgeon engagement of medical students should be emphasized,
      ideally before the third year of medical school.

PMID- 18317157
TI  - Plastic and reconstructive surgery goes multilingual: translations of articles
      into Spanish and Portuguese.

PMID- 18317161
TI  - The fat compartments of the face: anatomy and clinical implications for cosmetic
      surgery.

PMID- 18317162
TI  - Factors influencing the incidence of local wound complications following tissue
      expander/implant reconstruction.

PMID- 18317163
TI  - Breast implants and surgical drainage.

PMID- 18317164
TI  - Split turnover pectoralis muscle flap for the treatment of sternal osteomyelitis.

PMID- 18317167
TI  - Efficacy of a local anesthetic pain pump in abdominoplasty.

PMID- 18317168
TI  - Cervical necrotizing fasciitis.

PMID- 18317171
TI  - The transverse radial artery forearm flap.

PMID- 18317173
TI  - The distally based sural musculoneurocutaneous flap for treatment of distal
      tibial osteomyelitis.

PMID- 18317174
TI  - Inhibitory effect of minocycline on hypertrophic scarring.

PMID- 18317175
TI  - Corrections to the birth of plastic surgery.

PMID- 18317177
TI  - Non possum sequi tibi! Where am I going if I cannot follow you?

PMID- 18317179
TI  - Resistive simulated weightbearing exercise with whole body vibration reduces
      lumbar spine deconditioning in bed-rest.
AB  - STUDY DESIGN: Randomized controlled trial. OBJECTIVE: Determine the effectiveness
      a resistive exercise countermeasure with whole-body vibration in relation to
      lumbo-pelvic muscle and spinal morphology changes during simulated spaceflight
      (bed-rest). SUMMARY OF BACKGROUND DATA: Spinal lengthening, flattening of the
      spinal curves, increases in disc size, and muscle atrophy are commonly seen in
      spaceflight simulation. This may represent a risk for low back injury.
      Consideration of exercise countermeasures against these changes is critical for
      success of long-term spaceflight missions. METHODS: Twenty healthy male subjects
      underwent 8-weeks of bed-rest with 6-months follow-up and were randomly allocated
      to an inactive control or countermeasure exercise group. Magnetic resonance
      imaging of the lumbo-pelvic region was conducted at regular time-points during
      and after bed-rest. Using uniplanar images at L4, cross-sectional areas of the
      multifidus, lumbar erector spinae, quadratus lumborum, psoas, anterolateral
      abdominal, and rectus abdominis muscles were measured. Sagittal scans were used
      to assess lumbar spine morphology (length, sagittal disc area and height, and
      intervertebral angles). RESULTS: The countermeasure group exhibited less
      multifidus muscle atrophy (P = 0.024) and its atrophy did not persist long-term
      as in the control group (up to 3-months; P < 0.006). Spinal lengthening (P =
      0.03) and increases in disc area (P = 0.041) were also reduced. Significant
      partial correlations (P < 0.001) existed between spinal morphology and muscle
      cross-sectional area changes. CONCLUSION: The resistive vibration exercise
      countermeasure reduced, but did not entirely prevent, multifidus muscle atrophy
      and passive spinal tissue deconditioning during bed-rest. Atrophy of the
      multifidus muscles was persistent long-term in the inactive subjects. Future work
      could consider closer attention to spinal posture during exercise and optimizing
      exercise dose.

PMID- 18317180
TI  - Surgical treatment of vertebral osteomyelitis with recombinant human bone
      morphogenetic protein-2.
AB  - STUDY DESIGN: A retrospective clinical study. OBJECTIVE: To evaluate the use of
      recombinant human bone morphogenetic protein-2 (rhBMP-2) as the primary graft
      material for the surgical treatment of vertebral osteomyelitis. SUMMARY OF
      BACKGROUND DATA: The clinical and radiographic results using allograft,
      autograft, and vascularized bone flaps for the surgical treatment of
      osteomyelitis have been previously reported. Despite an expanding body of
      literature documenting the value of rhBMP-2 in spinal fusion, its application to
      the management of spinal infection has never before been analyzed. METHODS:
      Twenty patients underwent surgical treatment of vertebral osteomyelitis using
      rhBMP-2 and were analyzed with a mean follow-up of 40 months (range, 24-53
      months). All patients were treated with anterior column debridement and
      instrumented reconstruction. Four (20%) patients were treated with an anterior
      approach alone while the remaining 16 (80%) patients underwent circumferential
      spinal reconstruction. Clinical outcomes were assessed by Frankel grade and Odom
      criteria. Radiographic fusion was characterized based on thin-section
      computerized tomography (CT) analysis. RESULTS: Pathogens responsible for
      infection included Staphylococcus aureus (11; 55%), S. epidermidis (6; 30%),
      Bacteroides (1; 5%), and polymicrobial species (1; 5%). Infected segments of the
      spinal column based on region were found to be: thoracic (1; 5%), thoracolumbar
      (5; 25%), lumbar (11; 55%), and lumbosacral (3; 15%). The mean number of anterior
      and posterior segments fused was 3.3 (range, 2-5) and 6.5 (range 2-16),
      respectively. Forty-five percent of the subjects underwent multilevel
      corpectomies and fusion. All patients demonstrated clinical and radiographic
      evidence of spinal fusion at the time of follow-up. Patients had stable (14
      patients) or improved (6 patients) Frankel grades after surgery. Odom criteria at
      final follow-up were: excellent (3; 15%), good (12; 60%), fair (4; 20%), and poor
      (1; 5%). There was no case of persistent or recurrent infection requiring
      revision surgery. CONCLUSION: rhBMP-2 is a valuable graft option for the surgical
      treatment of vertebral osteomyelitis. When dosed in the manner reported, very
      high rates of fusion are achievable as is eradication of infection.

PMID- 18317181
TI  - Missed lumbar disc herniations diagnosed with kinetic magnetic resonance imaging.
AB  - STUDY DESIGN: A novel dynamic magnetic resonance imaging (MRI) system, kinetic
      MRI (kMRI), was used to study lumbar disc herniations. OBJECTIVE: The objective
      of this study was to determine if adding flexion and extension MRI studies to the
      traditional neutral views would be beneficial in the diagnosis of lumbar disc
      herniations. SUMMARY OF BACKGROUND DATA: Prior studies demonstrate that only 70%
      of patients with lumbar disc herniations based on physical examinations are
      confirmed by MRI studies. Recently, kMRI delivers the ability to scan patients in
      neutral, flexion, and extension positions, which may allow for improved diagnosis
      of this problem. METHODS: Five hundred fifty-three patients underwent kMRI with
      assessment of the degree of disc bulge in neutral and flexion and extension. The
      images were analyzed using computer measurement technology to objectively
      quantify the amount of disc herniation. RESULTS: For patients with normal or <3
      mm of disc bulge in neutral, 19.46% demonstrated an increase in herniation to >3
      mm bulge in extension, and 15.29% demonstrated an increase to >3 mm bulge in
      flexion. For patients in the neutral view that had a baseline disc bulge of 3 to
      5 mm, 13.28% had increased herniations to >5 mm in extension and 8.47% had
      increased herniations to >5 mm in flexion. For patients with a baseline disc
      bulge of 5 to 7 mm in neutral, 10.58% increased in extension and 5.78% increased
      in flexion. In addition, for patients with a baseline disc bulge of 7 to 9 mm in
      neutral, 9.09% increased in extension and 4.55% increased in flexion. CONCLUSION:
      A significant increase in the degree of lumbar disc herniation was found by
      examining flexion and extension views when compared with neutral views alone.
      kMRI views provide valuable added information, especially in situations where
      symptomatic radiculopathy is present without any abnormalities demonstrated on
      conventional MRI.

PMID- 18317182
TI  - Physical characteristics of women with severe pelvic girdle pain after pregnancy:
      a descriptive cohort study.
AB  - STUDY DESIGN: Descriptive cohort study. OBJECTIVE: This study aims to further
      elucidate the differences in physical characteristics of women with severe
      pregnancy-related pelvic girdle pain (PGP). SUMMARY OF BACKGROUND DATA: There is
      increasing interest in pelvic girdle pain (PGP). To our knowledge, this is the
      first study on a large population of patients with severe PGP, after pregnancy,
      based on high cutoff scores on diagnostic PGP tests. METHODS: Two hundred five
      patients were selected from the outpatient clinic of a rehabilitation center.
      Patients were divided in 3 inclusion groups based on the total number of positive
      scores on 5 diagnostic tests; i.e., active straight leg raise test, posterior
      pelvic pain provocation test, long dorsal sacroiliac ligament test, and hip
      abduction and adduction strength tests. These inclusion groups were related to
      the data on trunk strength test, general provocation tests, Quebec Back Pain
      Disability Scale (QBPDS) and activities of daily living. RESULTS: A typical
      pattern of PGP emerges from this study. The mean group score on the active
      straight leg raise, posterior pelvic pain provocation, and long dorsal sacroiliac
      ligament tests became higher when more than 3 inclusion tests were positive. Hip
      abduction and adduction strength became lower with more positive tests. The QBPDS
      score was overall high and significantly higher for 5 positive tests compared
      with 3 and 4 positive tests. This shows that the number of positive tests, the
      individual score on the diagnostic tests, and the QBPDS could all be an indicator
      for severity of PGP. Among the general pain provocation tests, both the passive
      hip flexion test and the upper and middle sacral thrust test scored high. The
      maximal isometric strength of trunk muscles was below the 10th percentile
      compared with women without complaints and was even less for 5 positive inclusion
      tests. It is confirmed that there is a typical order for difficulties with daily
      activities for PGP patients as follows (most difficult first): standing still,
      cycling, walking, sitting, and lying. CONCLUSION: The study shows that the level
      of severity in PGP can be adequately assessed by a combination of specific tests.

PMID- 18317183
TI  - Kummell's disease: a case report and literature review.
AB  - STUDY DESIGN: A case report and literature review of Kummell's disease.
      OBJECTIVE: To describe a case that meets modern criteria for Kummell's disease
      and discuss the literature on this. SUMMARY OF BACKGROUND DATA: Over 100 years
      ago, Hermann Kummell described a condition in which patients sustained a
      "trivial" trauma, had an essentially asymptomatic period lasting weeks to months,
      then developed a painful, progressive angular kyphosis. Only with the advent of
      radiograph technology, and the radiographic demonstration of delayed vertebral
      body collapse, was this concept felt to be valid. There has been a renewed
      interest in this as a diagnostic entity. METHODS: A patient is presented who
      developed worsening midback pain weeks after a minor fall. He subsequently was
      found to have T9, and T10 destructive vertebral body lesions. RESULTS: Only after
      an extensive workup, including 3 biopsies of the affected area was the diagnosis
      of Kummell's disease considered and surgical treatment performed. CONCLUSION.:
      Delayed vertebral body collapse, i.e., Kummell's disease, needs to be considered
      in any patient with recurrent or worsening spinal symptoms. Under-recognition of
      this condition leads to delayed diagnosis and treatment.

PMID- 18317184
TI  - Infection-related atlantoaxial subluxation (Grisel syndrome) in an adult with
      Down syndrome.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report an adult case with Down syndrome,
      in whom infection-related atlantoaxial subluxation (Grisel syndrome) developed.
      SUMMARY OF BACKGROUND DATA: Atlantoaxial instability is a common complication in
      Down syndrome patients; however, there have been limited reports of adult-onset
      atlantoaxial subluxation with myelopathy. Grisel syndrome has been characterized
      as a nontraumatic atlantoaxial subluxation associated with pharyngeal infection.
      It usually affects children, and the subluxation can be successfully reduced by
      conservative treatments in most cases. METHODS: A 26-year-old man with Down
      syndrome suffered from retropharyngeal infection, after which his atlantoaxial
      subluxation was aggravated and myelopathy developed. He was treated with
      administration of antibiotics and application of a halo-vest. RESULTS: The
      conservative treatments failed to reduce the atlantoaxial subluxation. We
      performed a C1 laminectomy and posterior occipitocervical fusion, which
      successfully relieved his symptoms. CONCLUSION.: This experience suggests that
      when Down syndrome patients have retropharyngeal infection, we should consider
      the possible aggravation of atlantoaxial instability and development of
      myelopathy, even if the patient is an adult.

PMID- 18317186
TI  - The value of spine implant retrieval analysis.

PMID- 18317187
TI  - Anterior cervical discectomy with or without fusion with ray titanium cage: a
      prospective randomized clinical study.
AB  - STUDY DESIGN: A prospective randomized clinical study. OBJECTIVE: To compare 2
      surgical methods in the treatment of cervical radiculopathy caused by hard or
      soft disc herniation; namely, simple discectomy versus discectomy with an
      additional interbody fusion with a Ray titanium cage. SUMMARY OF BACKGROUND DATA:
      Although an interbody fusion after anterior decompressive surgery for hard or
      soft disc herniation is widely accepted, there is no scientific evidence that
      convincingly demonstrates that insertion of graft material for interbody fusion
      is necessary after discectomy and decompression of the nervous elements have been
      performed. To date, no randomized studies have compared simple discectomy with
      discectomy followed by an interbody fusion with a titanium cage. METHODS: Eighty
      six patients with symptoms of nerve root compression at 1 level were randomly
      allocated to either discectomy followed by fusion with a Ray titanium cage (40
      patients) or to discectomy alone (46 patients). Clinical and radiologic follow-up
      was performed 3, 12, and 24 months after surgery. RESULTS: There was no
      statistically significant difference between the 2 groups concerning self
      reported satisfaction or severity of pain in the neck and arm. Two years after
      the operation, 86.1% of the patients treated with cage stated a good outcome
      versus 76.7% in the discectomy group (P = 0.44). The rate of fusion was 83.3% in
      the cage group versus 81.0% in the discectomy group (P = 0.30). Furthermore,
      after 2 years, also the rates of new adjacent disc degeneration or spondylosis
      were the same in both groups. CONCLUSION: This study showed no statistically
      significant difference between simple discectomy and discectomy followed by
      interbody fusion with a titanium cage in the surgical treatment of cervical
      radiculopathy caused by disc herniation.

PMID- 18317188
TI  - Anterior cervical fusion with tantalum implant: a prospective randomized
      controlled study.
AB  - STUDY DESIGN: A prospective randomized controlled study was carried out.
      OBJECTIVE: To determine the effectiveness and safety of a tantalum implant in
      achieving anterior cervical fusion following 1-level discectomy as treatment of
      degenerative cervical disc disease with radiculopathy. SUMMARY OF BACKGROUND
      DATA: The gold standard for the treatment of degenerative cervical disc disease
      could not be already identified. The morbidity of autologous graft and plating,
      and the doubt about the mechanical efficacy of plate fixation and the clinical
      benefits in 1-level fusion have promoted the use of other constructs. METHODS:
      Sixty-one patients were randomized to anterior cervical discectomy and fusion
      with interbody implant of tantalum (n = 28) or by means of autologous iliac bone
      graft and plating (n = 33). Fusion rate and segmental height and alignment were
      blind assessed by radiographs by 2 independent reviewers. Clinical status was
      evaluated using pain visual analogue scale, the Neck Disability Index, and the
      Zung Depression Scale. Patient's subjective satisfaction was recorded.
      Complications and operative parameters were also taken into account. RESULTS:
      With an endpoint of 24 months, radiologic and clinical outcomes were similar for
      both treatments without significant difference. The safety of fusion with
      tantalum implant was obvious, based on the analysis of complications.
      Complication rate was considerably higher for the autologous graft plus plating
      procedure than for implant tantalum (P < 0.005). CONCLUSION: The efficacy to
      achieve fusion after 1-level anterior cervical discectomy, with a good radiologic
      and clinical outcome, using tantalum implant is equivalent to that of autologous
      graft and anterior plate, being safer as avoids donor-site graft harvesting and
      plating complications.

PMID- 18317189
TI  - Effects of two guideline implementation strategies on patient outcomes in primary
      care: a cluster randomized controlled trial.
AB  - STUDY DESIGN: Cluster randomized controlled trial. OBJECTIVE: To improve quality
      of care for patients with low back pain (LBP) a multifaceted general practitioner
      education alone and in combination with motivational counseling by practice
      nurses has been implemented in German general practices. We studied effects on
      functional capacity (main outcome), days in pain, physical activity, quality of
      life, or days of sick leave (secondary outcomes) compared with no intervention.
      SUMMARY OF BACKGROUND DATA: International research has lead to the development of
      the German LBP guideline for general practitioners. However, there is still doubt
      about the most effective implementation strategy. Although effects on process of
      care have been observed frequently, changes in patient outcomes are rarely seen.
      METHODS: We recruited 1378 patients with LBP in 118 general practices, which were
      randomized to 1 of 3 study arms: a multifaceted guideline implementation (GI), GI
      plus training of practice nurses in motivational counseling (MC), and the postal
      dissemination of the guideline (controls, C). Data were collected (questionnaires
      and patient interviews) at baseline and after 6 and 12 months. Multilevel mixed
      effects modeling was used to adjust for clustering of data and potential
      confounders. RESULTS: After 6 months, functional capacity was higher in the
      intervention groups with a cluster adjusted mean difference of 3.650 between the
      MC group and controls (95% CI = 0.320-6.979, P = 0.032) and 2.652 between the GI
      group and controls (95% CI = -0.704 to 6.007, P = 0.120). Intervention effects
      were more pronounced regarding days in pain per year with an average reduction of
      16 (GI) to 17 days (MC) after 6 months (12 and 9 days after 12 months) compared
      with controls. CONCLUSION: Active implementation of the German LBP guideline
      results in slightly better outcomes during 6 months follow-up than its postal
      dissemination. Results are more distinct when practice nurses are trained in
      motivational counseling.

PMID- 18317190
TI  - What is the correlation of in vivo wear and damage patterns with in vitro TDR
      motion response?
AB  - STUDY DESIGN: This study combined the evaluation of retrieved total disc
      replacements (TDRs) with a biomechanical study using human lumbar spines. Thirty
      eight CHARITE TDRs were retrieved from 32 patients after 7.3 years average
      implantation. All implants were removed because of intractable back pain and/or
      facet degeneration. In parallel, 20 new implants were evaluated at L4-L5 and L5
      S1 in an in vitro lumbar spine model. OBJECTIVE: The purpose of this study was to
      correlate wear and damage patterns in retrieved TDRs with motion patterns
      observed in an in vitro lumbar spine model. We also sought to determine whether
      one-sided wear and motion patterns were associated with greater in vivo wear.
      SUMMARY OF BACKGROUND DATA: The comparison of polyethylene wear in TDRs after
      long-term implantation to those tested using an in vitro model had not yet been
      investigated. METHODS: The wear patterns of each retrieved PE core was analyzed
      at the rim and dome. Thirty-five cores were further analyzed using MicroCT to
      determine the penetration symmetry. For the in vitro study the implants were
      tested under physiologic loads using a validated cadaveric model. Motion patterns
      of the in vitro-tested implants were tracked using sequential video-fluoroscopy.
      RESULTS: Fifteen of 35 retrieved cores (43%) displayed one-sided wear patterns.
      Significant correlations were observed between implantation time and penetration
      and penetration rate. In the in vitro study, there was evidence of motion at both
      articulations, motion at both articulation but predominantly at the top
      articulation, and solelyat the top articulation. Core entrapment and pinching was
      observed and associated with visual evidence of core bending or deformation.
      CONCLUSION: This is the first study to directly compare the long-term PE wear and
      damage mechanisms in TDR retrievals with the motion patterns generated by a
      validated in vitro cadaveric testing model. The retrievals exhibited wear
      patterns consistent with the in vitro testing.

PMID- 18317191
TI  - Normative segment-specific axial and coronal angulation corridors of subaxial
      cervical column in axial rotation.
AB  - STUDY DESIGN: In contrast to clinical studies wherein loading magnitudes are
      indeterminate, experiments permit controlled and quantifiable moment
      applications, record kinematics in multiple planes, and allow derivation of
      moment-angulation corridors. Axial and coronal moment-angulation corridors were
      determined at every level of the subaxial cervical spine, expressed as
      logarithmic functions, and level-specificity of range of motion and neutral zones
      were evaluated. OBJECTIVE:  HYPOTHESIS: segmental primary axial and coupled
      coronal motions do not vary by level. SUMMARY OF BACKGROUND DATA: Although it is
      known that cervical spine responses are coupled, segment-specific corridors of
      axial and coronal kinematics under axial twisting moments from healthy normal
      spines are not reported. METHODS: Ten human cadaver columns (23-44 years, mean:
      34 +/- 6.8) were fixed at the ends and targets were inserted to each vertebra to
      obtain kinematics in axial and coronal planes. The columns were subjected to pure
      axial twisting moments. Range of motion and neutral zone for primary-axial and
      coupled-coronal rotation components were determined at each spinal level. Data
      were analyzed using factorial analysis of variance. Moment-rotation angulations
      were expressed using logarithmic functions, and mean +/-1 standard deviation
      corridors were derived at each level for both components. RESULTS: Moment
      angulations responses were nonlinear. Each segmental curve for both components
      was well represented by a logarithmic function (r2 > 0.95). Factorial analysis of
      variance indicated that the biomechanical metrics are spinal level-specific (P <
      0.05). CONCLUSION: Axial and coronal angulations of cervical spinal columns show
      statistically different level-specific responses. The presentation of moment
      angulation corridors for both metrics forms a dataset for the normal population.
      These segment-specific nonlinear corridors may help clinicians assess dysfunction
      or instability. These data will assist mathematical models of the spine in
      improved validation and lead to efficacious design of stabilizing systems.

PMID- 18317192
TI  - Apolipoprotein E gene polymorphism and the risk of cervical myelopathy in
      patients with chronic spinal cord compression.
AB  - STUDY DESIGN: Prospective evaluation of apolipoprotein E (APOE) genotypes in 106
      consecutive patients with stenosis of the cervical spinal canal. OBJECTIVE: To
      determine the association between cervical spondylotic myelopathy (CSM) in
      patients with chronic spinal cord compression and the APOE genotype. SUMMARY OF
      BACKGROUND DATA: The APOE allele epsilon 4 is a risk factor for the occurrence,
      progression, and poor outcome in several neurologic diseases. Information of the
      association between APOE genotype and CSM in the literature are lacking so far.
      METHODS: One hundred six consecutive patients with chronic cervical spinal cord
      compression due to stenosis of the spinal canal were evaluated prospectively.
      APOE genotypes were determined by polymerase chain reaction followed by
      restriction enzyme digestion and sodiumdodecylsulfate poyacrylamide gel
      electrophoresis (SDS PAGE) of digested fragments. Clinical and radiologic
      variables evaluated were age, occurrence of CSM, duration of symptoms, number of
      affected segments, and diameter of spinal canal of most affected segment.
      Univariate association between variables was tested. A backward stepwise method
      was used to construct multivariate logistic regression models in relation to the
      occurrence of CSM as dependent variable. RESULTS: The following distribution of
      APOE genotypes was found: epsilon 2 epsilon 2 3 patients (2.8%), epsilon 2
      epsilon 3 9 patients (8.5%), epsilon 2 epsilon 4 1 patient (0.9), epsilon 3
      epsilon 3 67 patients (63.2%), epsilon 3 epsilon 4 24 patients (22.6%), epsilon 4
      epsilon 4 2 patients (1.9%). Univariate analysis showed that patients with
      chronic spinal cord compression and homo- or heterozygous allele epsilon 4 are
      more likely to develop CSM than patients without allele epsilon 4 (65.0% vs.
      35.0%, P < 0008; OR 3.5; 95% CI 1.3-9.8). This effect remained significant in a
      binary logistic regression model adjusted to other known risk factors for CSM.
      Inclusion of the variable homo- or heterozygous epsilon 4 allele led to an
      increased goodness of fit of the model compared with the model without epsilon 4.
      CONCLUSION.: This study supports the hypothesis that the APOE epsilon 4 allele
      increases the risk of CSM in patients with chronic cervical spinal cord
      compression; however, a larger prospective population-based study is needed to
      answer this question definitively.

PMID- 18317193
TI  - The impact of adjacent segment degeneration on the clinical outcome after lumbar
      spinal fusion.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To determine the impact of the
      adjacent segment degeneration (ASD) on the clinical outcome after lumbar fusion.
      SUMMARY OF BACKGROUND DATA: Few studies have analyzed correlation between
      clinical outcomes and ASD. METHODS: From January 2000 to December 2004, 217
      patients who underwent lumbar fusion and have more than 2 years of follow-up were
      evaluated. The patients were divided into 3 groups: fusion was carried out on 1
      (A), 2 (B), and more than 3 segments (C). UCLA grading scale was used to evaluate
      the ASD on radiograph preoperative, postoperative, and last follow-up. The
      clinical outcome was evaluated and the association between clinical outcome and
      ASD was evaluated by the Spearman correlation. RESULTS: ASD occurred 11.6%
      (13/112 cases) in group A, 14.5% (9/62 cases) in group B, and 16.3% (7/43 cases)
      in group C. Among them, the cases which had progressed more than 2 level of
      degenerative grade were 0 in group A, 7 cases (77.8%) in group B, and 6 cases
      (85.7%) in group C. In group A, 5 cases with ASD had down graded 1 level in
      clinical outcome. In group B, all 9 cases with ASD had down graded more than 1
      level in clinical outcome; 1 level aggravation in 1, 2 level in 5, and 3 level in
      1 case. In group C, all 7 cases with ASD also had down graded more than 1 level
      in clinical outcome; 1 level aggravation in 2, 2 level in 5 cases. Finally, the
      more the change of the degenerative grade is severe, the more the clinical
      outcome is worse (P < 0.05). CONCLUSION: The impact of ASD on clinical outcome
      after fusion showed a significant correlation, especially with the ASD after
      multiple-segments fusion. Careful attention is needed in multiple-segments fusion
      such as degenerative lumbar deformity.

PMID- 18317194
TI  - Effect of intervertebral disc height on postoperative motion and outcomes after
      ProDisc-L lumbar disc replacement.
AB  - STUDY DESIGN: Retrospective study of patients enrolled in prospective randomized
      Food and Drug Administration trial. OBJECTIVE: To evaluate the influence of pre-
      and postoperative disc height on postoperative motion and clinical outcomes.
      SUMMARY OF BACKGROUND DATA: Our understanding of the factors that influence
      motion and ultimately patient satisfaction after lumbar disc replacement
      continues to evolve. METHODS: Forty-two patients with a single level ProDisc-L at
      either the L4/5 or L5-S1 were selected. Pre- and postoperative disc height and
      range of motion (ROM) were measured from standing lateral and flexion-extension
      radiographs. Oswestry Disability Index and visual analog scale were also
      collected. Student t test and Spearman rho tests were performed to determine if
      there was any correlation or "threshold" effect between the disc height and ROM
      or clinical outcome. RESULTS: The mean anterior and posterior disc height
      significantly increased from 10.8 mm to 17.6 mm and 4.4 mm to 7.9 mm,
      respectively (P < 0.01). The mean ROM decreased from 7.0 degrees to 5.7 degrees
      (P = 0.21). Patients with less than 9 mm of preoperative anterior disc height had
      an increase in their ROM (2.2 degrees) compared with a loss of ROM (-2.2 degrees)
      in patients with more than 9 mm of preoperative disc height (P = 0.02). Patients
      with between 16 mm and 18 mm of postoperative anterior disc height have greater
      ROM (7.5 degrees) than those above or below this range (3.6 degrees and 3.6
      degrees respectively, P < 0.05). There was no correlation or threshold effect
      between clinical outcomes and disc height. CONCLUSION: Patients with greater disc
      collapse benefit more in ROM from a total disc replacement. The optimal range to
      maximize ROM for postoperative anterior disc height is 16 mm to 18 mm. This
      optimal range did not translate into better clinical outcome at 2 years follow
      up.

PMID- 18317196
TI  - Long-term outcomes of two different decompressive techniques for lumbar spinal
      stenosis.
AB  - STUDY DESIGN: A prospective study to evaluate the outcomes of 2 different
      decompressive techniques for lumbar spinal stenosis. OBJECTIVE: To explore a more
      effective and less invasive decompression technique without instrument and fusion
      for lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: The traditional surgical
      decompression of spinal stenosis involves laminectomy or unilateral laminotomy.
      Even in unilateral laminotomy cases, 85.3% had an excellent-to-fair operative
      result, and the incidence of complications was 9.8%. Although the addition of
      instrumentation does not increase the complication rate, but compared to the
      efficiency, the higher costs was controversial. Minimal invasion and
      destabilization are recommended. METHODS: This prospective study included 152
      consecutive patients, sequentially divided into 2 groups, underwent Windows
      technique (group A) and decompressive laminectomy (group B) by 2 groups of
      surgeons. RESULTS: The evaluation of the back pain, leg pain, walking tolerance,
      and neurologic recovery were performed before surgery and after surgery. In group
      A, at the final evaluation, the overall results were good to excellent in 89%
      (68/76) of the patients, fair 11% (8/76), and poor 0%. In group B, at the final
      evaluation, the overall results were good to excellent in 63% (48/76) of the
      patients, fair 30% (23/76), and poor 7% (5/76). CONCLUSION: Degenerative spinal
      stenosis can be decompressed adequately with preserving the posterior elements.
      The "Windows technique" laminoforaminotomy, which obtained satisfactory long-term
      outcomes with few complications and low cost, can be a standard procedure for the
      surgical treatment of the degenerative spinal stenosis even with slight
      congenital spinal stenosis.

PMID- 18317197
TI  - Incidence and risk factors of neurological deficits of surgical correction for
      scoliosis: analysis of 1373 cases at one Chinese institution.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the incidence of
      neurologic deficits after scoliosis correction at 1 institution and identify the
      risk factors for such deficits in scoliosis correction. SUMMARY OF BACKGROUND
      DATA: Neurologic deficit is one of the risks of surgical correction of scoliosis.
      Reports of the incidence of the neurologic deficits involving a large number of
      cases at 1 institution are rare. METHODS: Statistical analysis of the neurologic
      deficits was performed in 1373 scoliosis cases treated at 1 institution by
      etiologies in light of the patients' sex, age, sagittal profile, surgical
      approach, Cobb's angle, and the type of surgery. RESULTS: The total incidence of
      neurologic deficits was 1.89% and that of serious and mild ones was 0.51% and
      1.38%, respectively. The total incidence of neurologic deficits were 1.06% in
      adolescent idiopathic scoliosis patients and 2.89% in congenital scoliosis (CS)
      patients, 3.32% in scoliosis patients with hyperkyphosis (>40 degrees ) and 1.38%
      in those without hyperkyphosis, 3.43% for combined procedures and 1.24% for
      single posterior procedures, 3.69% in patients with Cobb's angle more than 90
      degrees and 1.45% in those with an angle less than 90 degrees , 1.68% with
      primary surgery and 5.97% with revision surgery, the difference between them was
      significant (P < 0.05). In adolescent idiopathic scoliosis patients, the
      incidence were 3.85% for combined procedures and 0.64% for posterior procedure,
      0.82% with primary surgery and 8.33% with revision surgery, 4.17% with
      hyperkyphosis and 0.61% without hyperkyphosis, the difference between them was
      significant (P < 0.05). The incidence of CS patients with Cobb's angle more or
      less than 90 degrees were 7.23% and 1.68% and the difference was significant (P <
      0.05). CONCLUSION: In surgical correction of scoliosis, the risk factors for
      neurologic deficits include CS, scoliosis with hyperkyphosis, scoliosis
      correction by combined procedures, scoliosis with a Cobb's angle more than 90
      degrees , and a revision surgery.

PMID- 18317198
TI  - Is smoking a risk factor for low back pain in adolescents? A prospective cohort
      study.
AB  - STUDY DESIGN: A prospective cohort study in adolescents. OBJECTIVE: To evaluate
      whether smoking in adolescence is a risk factor of low back pain (LBP) among
      young adults. SUMMARY OF BACKGROUND DATA: Smoking has been found to associate
      with LBP among adults. Longitudinal studies performed in adolescents are few.
      METHODS: The children belonging to the northern Finland Birth Cohort 1986 were
      examined at birth and at 16 years of age and followed up by a postal
      questionnaire at the age of approximately 18 years. The primary outcome was LBP
      during the past 6-month period. Incident cases reported LBP at 18 but not at 16
      years. Persistent cases reported pain at both time points. Logistic regression
      analysis was used to evaluate the effect of smoking exposure on any LBP in both
      genders separately and multinomial regression analysis was used to evaluate the
      effect on the severity of LBP (No LBP, "Reporting LBP," "Consultation for LBP")
      in the total population. Parents' socioeconomic status, physical activity, body
      mass index, and depressive mood were used as confounders in the analyses.
      RESULTS: Regular smoking at 16 years was associated with persistent LBP in girls
      (OR: 2.52; 95% CI: 1.40-4.53). Daily smoking of over 9 cigarettes at 16 was
      associated with persistent LBP (2.57; 1.03-6.46) and predicted incident pain in
      girls (2.80; 1.11-7.09). Pack-years of smoking were associated with incident and
      persistent LBP in the girls with an exposure-response relationship, whereas these
      associations were inconsistent in the boys. Pack-years of smoking at 18 years
      showed an exposure-response relationship with persistent Consultation for LBP,
      which was strongest in those with over 1.5 pack-years of exposure (5.82; 1.39
      24.42). CONCLUSION: Regular smoking in adolescence was associated with LBP in
      young adults. Pack-years of smoking showed an exposure-response relationship
      among girls.

PMID- 18317199
TI  - Correlation of measures of pain, function, and overall response: results pooled
      from two identical studies of etoricoxib in chronic low back pain.
AB  - STUDY DESIGN: Assessment of correlation of measures of low back pain (LBP) using
      data pooled from 2 identical studies. OBJECTIVE: To assess the relative
      responsiveness of and correlation between various measures of LBP, including the
      Roland-Morris Disability Questionnaire (RMDQ), the LBP intensity (LBPI) visual
      analog scale (VAS), and patient's global assessment of response to therapy
      (PGART). SUMMARY OF BACKGROUND DATA: Several tools are available to measure pain,
      functional limitation, and response to therapy for LBP. Studies have shown
      varying degrees of responsiveness and correlation. METHODS: This was a pooled
      subgroup analysis of patients with chronic LBP from 2 identical studies comparing
      etoricoxib 60 mg, 90 mg, and placebo. LBP was assessed by the time-weighted
      average change from baseline over 12 weeks as measured by RMDQ, LBPI VAS, and
      PGART. Correlation was calculated using Pearson's correlation coefficient.
      RESULTS: The correlation (r) between LBPI and RMDQ changes ranged from 0.657 and
      0.703; correlations between LBPI and PGART changes ranged from 0.677 and 0.738.
      Cutpoints separating responders from nonresponders for all 3 measures fell near
      the 66.7th percentile of response and were consistent with minimal clinically
      significant changes identified in the literature. CONCLUSION: In this study, the
      RMDQ, LBPI VAS, and PGART showed a high degree of correlation in measuring
      response to therapy in LBP, suggesting clinicians may be able to simplify
      assessments.

PMID- 18317200
TI  - Prevalence and risk factors associated with low back pain among health care
      providers in a Kuwait hospital.
AB  - STUDY DESIGN: A cross-sectional survey among health professionals working in a
      Kuwait hospital. OBJECTIVE: To investigate the prevalence and factors associated
      with low back pain (LBP). SUMMARY OF BACKGROUND DATA: The literature suggests
      that health professionals are exposed to occupational risk factors that
      predispose them to developing LBP. These rates are not well established in Middle
      Eastern countries such as Kuwait. METHODS: A self-administered survey was
      conducted with health professionals in an urban orthopedic hospital. RESULTS: The
      response rate to the survey was 60% (n = 344). Lifetime prevalence of LBP in the
      sample was 70.9%, and point prevalence of LBP was 21.5%. Factors associated with
      acute LBP included direct patient contact (P = 0.015), performing patient lifts
      and/or transfers (P = 0.016), low job satisfaction (P = 0.039), and poor self
      reported health status (P = 0.019). The prevalence ratio (PR) of reporting acute
      LBP was also found to increase as a function of the number of daily
      lifts/transfers performed (PR: 1.4; 95% CI: 1.27 to 1.70). Other factors
      generally associated with LBP, such as age, sex, professional experience, smoking
      and exercise, were not found to be significantly associated with LBP in this
      study. CONCLUSION: No causal relationships can be inferred using these cross
      sectional data. However, results suggest that direct patient contact that
      includes lifting and/or transferring patients may be an important risk factor.
      Further research is warranted to evaluate effectiveness of back education and
      prevention programs among hospital staff in Kuwait.

PMID- 18317201
TI  - The role of physical fitness as risk indicator of increased low back pain
      intensity among people working with physically and mentally disabled persons: a
      30-month prospective study.
AB  - STUDY DESIGN: A prospective cohort study. OBJECTIVE: To study if low level of
      physical fitness was associated with increased low back pain (LBP) intensity at
      30-month follow-up. SUMMARY OF BACKGROUND DATA: The evidence of low physical
      fitness as a risk factor for LBP is inconclusive due to contradictory results.
      METHODS: Study participants were 327 employees (women = 271, men = 56) at
      institutions for physically and mentally disabled persons. Physical fitness was
      measured by tests of: back extension and flexion endurance, flexibility and
      balance; and by self-assessed aerobic fitness, muscle strength, endurance,
      flexibility and balance, using visual analogue scales. Low back pain, lifestyle
      parameters, and physical and psychosocial work factors were assessed by
      questionnaires at baseline and at follow-up. Outcome was defined as an increase
      above 2 steps in average LBP intensity during the previous year (0-10). RESULTS:
      Persons with low level back endurance showed an insignificantly higher risk of
      increased LBP intensity (OR = 2.4, P = 0.076), whereas persons with medium level
      back endurance were at significantly higher risk (OR = 2.7, P = 0.034) compared
      with those with high level back endurance. The general association between
      isometric back extension endurance and increased LBP intensity was insignificant
      (P = 0.067). Persons with medium level self-assessed aerobic fitness were at
      lower risk of increased LBP intensity compared with those with high level (OR =
      0.37, P = 0.02), although the general association of aerobic fitness was
      insignificant (0.066). Performance-based back flexion endurance, flexibility, and
      balance; and self-assessed muscle strength, endurance, flexibility, and balance
      were not associated with increased LBP intensity. CONCLUSION: The significant
      association between medium level back extension endurance and increased LBP
      intensity supports the finding of other studies that particularly back extension
      endurance is an important physical fitness component in preventing LBP and that
      the subcomponents of physical fitness are related in different ways to LBP.

PMID- 18317202
TI  - Neck movement and muscle activity characteristics in female office workers with
      neck pain.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: To explore aspects of cervical
      musculoskeletal function in female office workers with neck pain. SUMMARY OF
      BACKGROUND DATA: Evidence of physical characteristics that differentiate computer
      workers with and without neck pain is sparse. Patients with chronic neck pain
      demonstrate reduced motion and altered patterns of muscle control in the cervical
      flexor and upper trapezius (UT) muscles during specific tasks. Understanding
      cervical musculoskeletal function in office workers will better direct
      intervention and prevention strategies. METHODS: Measures included neck range of
      motion; superficial neck flexor muscle activity during a clinical test, the
      craniocervical flexion test; and a motor task, a unilateral muscle coordination
      task, to assess the activity of both the anterior and posterior neck muscles.
      Office workers with and without neck pain were formed into 3 groups based on
      their scores on the Neck Disability Index. Nonworking women without neck pain
      formed the control group. Surface electromyographic activity was recorded
      bilaterally from the sternocleidomastoid, anterior scalene (AS), cervical
      extensor (CE) and UT muscles. RESULTS: Workers with neck pain had reduced
      rotation range and increased activity of the superficial cervical flexors during
      the craniocervical flexion test. During the coordination task, workers with pain
      demonstrated greater activity in the CE muscles bilaterally. On completion of the
      task, the UT and dominant CE and AS muscles demonstrated an inability to relax in
      workers with pain. In general, there was a linear relationship between the
      workers' self-reported levels of pain and disability and the movement and muscle
      changes. CONCLUSION: These results are consistent with those found in other
      cervical musculoskeletal disorders and may represent an altered muscle
      recruitment strategy to stabilize the head and neck. An exercise program
      including motor reeducation may assist in the management of neck pain in office
      workers.

PMID- 18317203
TI  - Effects of fear of movement on spine velocity and acceleration after recovery
      from low back pain.
AB  - STUDY DESIGN: A cross-sectional assessment of the association between pain
      related fear and joint motions and their higher order derivatives in 88
      participants recently recovered from an episode of low back pain. OBJECTIVE: To
      determine how the psychological construct of pain-related fear maps to motor
      behavior in standardized reaching tasks. SUMMARY OF BACKGROUND DATA: Pain-related
      fear is a significant predictor of avoidance behavior and occupational disability
      in individuals with low back pain. However, it is not currently known how pain
      related fear maps to motor behavior. METHODS: Participants were tested at 4 weeks
      (+/-2 weeks) after resolution of a recent episode of back pain. Participants
      performed reaching tasks at comfortable and fast-paced movement speeds to 3
      targets (high, middle, low) located in a midsagittal plane. Three-dimensional
      joint motions of the thoracic spine, lumbar spine, and hip were recorded using an
      electromagnetic tracking device. Group differences in joint excursions, peak
      velocities, and accelerations were assessed using 2-group (high pain-related
      fear, low pain-related fear) x 2-hand (left, right) x 2-movement speed
      (comfortable-pace, fast-pace) x 3-target height (high, middle, low) multivariate
      analyses of variances. RESULTS: Individuals with high pain-related fear had
      smaller peak velocities and accelerations of the lumbar spine and hip joints for
      the fast-pace reaching trials. CONCLUSION: The present study provides important
      evidence that pain-related fear is a robust construct that clearly maps on to
      differences in peak velocity and acceleration of the lumbar spine even after
      resolution of back pain.

PMID- 18317204
TI  - Efficacy of intraoperative cell saver in decreasing postoperative blood
      transfusions in instrumented posterior lumbar fusion patients.
AB  - STUDY DESIGN: A retrospective study. OBJECTIVE: To determine the efficacy of
      using intraoperative cell saver in decreasing the need for blood transfusion.
      SUMMARY OF BACKGROUND DATA: Lumbar spine surgery is associated with potential
      large intraoperative blood loss, which may put patients at risk for blood
      transfusions. Preoperative autologous blood donation mitigates the need for
      allogenic blood transfusion, but does not eliminate it. Cell-saver use has been
      advocated to further reduce the need for transfusion, but recent reports have
      called its efficacy into question. METHODS: Data were collected from 188 patients
      undergoing consecutive instrumented lumbar laminectomy and fusion. One hundred
      and forty-one of these patients had cell saver used during their procedures,
      whereas 47 did not. In addition, previously published data from similarly treated
      patients were used for analysis. Operative blood loss, autologous and allogenic
      blood transfusions, discharge hematocrit, and patient factors were analyzed.
      RESULTS: A significant increase in the number of blood transfusions was found in
      the cell-saver group. The cell-saver group also had a significantly increased
      blood loss compared with the non-cell-saver group. Using analysis of covariance,
      we determined the effect of blood loss on the need for transfusion. The results
      showed that correcting for blood loss eliminated the significance in the
      transfusion difference, but cell saver still was not able to decrease the
      transfusion need. Comparing our current results with our previously published
      results also demonstrated no benefit of cell saver use. CONCLUSION: Use of cell
      saver in instrumented lumbar fusion cases was not able to decrease the need for
      blood transfusion. Cell-saver use was associated with a significantly higher
      blood loss.

PMID- 18317205
TI  - Re: Thiel H W, Bolton J E, Docherty S, et al. Safety of chiropractic manipulation
      of the cervical spine. Spine 2007;32:2375-8.

PMID- 18317206
TI  - Re: Becker C, Heidersdorf S, Drewlo S, et al. Efficacy of epidural perineural
      injections with autologous conditioned serum for lumbar radicular compression.
      Spine 2007;32:1803-8.

PMID- 18317208
TI  - Adenolipoma of the external female genitalia.
AB  - Adenolipoma of the skin is a rare variant of lipoma not yet reported to involve
      the external female genitalia. We report, for the first time, 2 cases of
      adenolipoma arising in or immediately adjacent to the vulva in women aged 41 and
      44 years. They are characterized by sparse mammaglobin immunoreactive eccrine
      sweat glands embedded within lobules of mature adipose tissue. This report brings
      attention to this novel soft tissue tumor in a site where fat and sweat glands
      are normal tissue constituents.

PMID- 18317209
TI  - Pagetoid lesions of the vulva: a collision between malignant melanoma and
      extramammary Paget disease.
AB  - Vulvar extramammary Paget disease (EMPD) is an intraepithelial carcinoma not
      frequently seen in conjunction with other primary tumors. Nevertheless, we are
      presenting a collision between malignant nodular melanoma and EMPD in the vulva
      of a 78-year-old gravida 6, para 6 woman with a medical history of chronic
      lymphocytic leukemia. The patient presented with vulvar irritation and a
      pigmented vulvar mass; biopsy confirmed the diagnosis of malignant melanoma.
      Peripheral to the main mass, the vulva grossly seemed erythematous, and the
      perineum seemed white and thickened. Multiple radial biopsies were taken to
      determine the extent of involvement by malignant melanoma, and these biopsies
      revealed that the "irritated" areas surrounding the melanoma were EMPD.
      Subsequently, a radical vulvectomy was performed, the margins of which were clear
      of both neoplasms. Five months later, bilateral groin adenopathy was biopsy
      proven to be metastatic melanoma and chronic lymphocytic leukemia, and the
      patient died 8 months after the radical vulvectomy.

PMID- 18317210
TI  - Adenoid squamous carcinoma (pseudoangiosarcomatous carcinoma) of the vulva: a
      rare but highly aggressive variant of squamous cell carcinoma-report of a case
      and review of the literature.
AB  - Pseudoangiosarcomatous squamous cell carcinoma is an unusual but aggressive
      variant of acantholytic squamous cell carcinoma of the vulva that mimics
      angiosarcoma on histology. We present a case of a 57-year-old woman with
      bilateral inguinal metastatic disease at the time of diagnosis, who died 4 months
      later because of distant metastatic disease to the lungs. Molecular analysis did
      not reveal any human papillomavirus infection. Because of the positive p53
      immunostaining and the association to lichen sclerosus and simple type of high
      grade vulvar intraepithelial neoplasia, alteration of p53 tumor suppressor gene
      might be involved in the pathogenesis of vulvar pseudoangiosarcomatous squamous
      cell carcinoma. However, further molecular studies are required.

PMID- 18317211
TI  - Concomitant malacoplakia and granuloma inguinale of the cervix in acquired immune
      deficiency syndrome.
AB  - We describe concomitant granuloma inguinale (GI) and malacoplakia of the cervix
      in 2 acquired immune deficiency syndrome (AIDS) patients aged 27 and 36 years.
      Both patients presented with a bloody foul-smelling vaginal discharge. Speculum
      examination confirmed cervical ulceration, prompting the diagnosis of cervical
      carcinoma in both patients. Cervical punch biopsies confirmed the characteristic
      features of GI; granulation tissue containing a dense plasma cell infiltrate,
      aggregates of neutrophils, and vacuolated enlarged histiocytes containing Donovan
      bodies were noted. Many of these histiocytes and sheets of von Hansemann cells
      contained intracytoplasmic Michaelis-Gutmann bodies, confirming concomitant
      malacoplakia. Michaelis-Gutmann bodies were also present in extracellular
      locations. Ultrastructural examination confirmed these histopathologic findings.
      One patient died of disseminated tuberculosis before treatment was initiated. The
      other patient did not return for a follow-up visit of her cervical lesion.
      Concomitant GI and malacoplakia is unreported in genital and extragenital sites;
      Klebsiella granulomatis must therefore be added to the list of bacteria
      associated with malacoplakia. Malacoplakia of the female genital tract is
      documented rarely and remains unreported, to date, in AIDS patients. Similar to
      the pathogenetic mechanisms described for AIDS-associated malacoplakia in
      extragenital sites, it is hypothesized that, in addition to abnormal macrophage
      functioning and an inability to degrade bacteria, special constituents of K.
      granulomatis are undigestable by lysosomal enzymes in human immunodeficiency
      virus-infected patients.

PMID- 18317212
TI  - Morphological effects of radiochemotherapy on cervical carcinoma: a morphological
      study of 50 cases of hysterectomy specimens after neoadjuvant treatment.
AB  - The introduction of radiochemotherapy for treatment of advanced cervical cancers
      represents a new chapter in surgical pathology. The study group included 50 women
      with a histological diagnosis of advanced cervical carcinoma (43 squamous, 3
      adenosquamous, 2 adenocarcinoma, 1 glassy cell, and 1 undifferentiated;
      International Federation of Gynecology and Obstetrics stage Ib-III) receiving a
      platinum-based chemotherapy concomitant with external beam radiotherapy before
      radical surgery. We evaluated the amount of residual neoplastic tissue, depth of
      invasion, presence of neoplastic embolism, number of metastatic lymph nodes, and
      alterations of the nonneoplastic stroma and epithelium. We observed neoplastic
      masses larger than 0.3 cm (no pathological response, pR2) in 14 cases (28%),
      single or multiple microscopic neoplastic residual (partial pathological
      response, pR1) in 24 cases (48%), and no invasive neoplastic cells (complete
      pathological response, pR0) in 12 cases (24%). Residual neoplastic cells showed a
      wide pattern of alterations such as cytoplasmic eosinophilia, vacuolation, and
      foamy appearance; the nuclei were enlarged and irregular with clumped chromatin.
      The mitotic activity was scanty. In some cases, multinucleated neoplastic giant
      cell coexisted with reactive foreign body-like giant cells. The stroma was
      fibrous containing inflammatory cells, fibrinous debris, cholesterol clefts,
      hemosiderin pigments, and microcalcifications. In just 2 cases, we found lymph
      node metastases. The pathologist has to distinguish neoplastic residuals from
      reactive changes. In most cases, morphological criteria are sufficient to make a
      diagnosis, but sometimes, the use of immunohistochemistry (keratins and CD68) is
      a mandatory method to reveal the nature of the lesion.

PMID- 18317213
TI  - Predicting high-risk human papillomavirus infection, progression of cervical
      intraepithelial neoplasia, and prognosis of cervical cancer with a panel of 13
      biomarkers tested in multivariate modeling.
AB  - Comprehensive multivariate models were used to disclose whether any of our
      previously analyzed 13 markers would be independent predictors of intermediate
      end point markers in cervical carcinogenesis. The expression of the following
      biomarkers, E-cadherin, extracellular signal-regulated kinase 1, 67-kd laminin
      receptor (LR67), matrix metalloproteinase 2, tissue inhibitor of
      metalloproteinase 2, nuclear factor-kappaB, nm23-H1, p16, proliferating cell
      nuclear antigen, survivin, human telomerase reverse transcriptase, topoisomerase
      2alpha, and vascular endothelial growth factor (VEGF) C in 150 cervical cancer
      (CC) and 152 cervical intraepithelial neoplasia (CIN) lesions were determined
      immunohistochemically. Multivariate models were constructed to test predictive
      power of the markers for 3 outcomes: (1) high-grade CIN, (2) high-risk human
      papillomavirus (HR-HPV), and (3) CC survival. Performance indicators were
      calculated and compared by the areas under receiver operating characteristic
      (ROC) curve. Three marker panels were identified consisting of 5 independent
      predictors of CIN2 (E-cadherin, extracellular signal-regulated kinase 1, LR67,
      topoisomerase 2alpha, and VEGF-C), 3 predictors of HR-HPV (survivin, p16, and
      human telomerase reverse transcriptase), and 2 predictors of CC survival (nm23-H1
      and tissue inhibitor of metalloproteinase 2). In predicting CIN2, the best
      balance between sensitivity (SE) and specificity (SP) was obtained by combining
      the 2 most powerful predictors in panel 1 (VEGF-C and LR67), giving the area
      under ROC curve, 0.897 (95% confidence interval [CI], 0.847-0.947); odds ratio,
      86.27 (95% CI, 19.71-377.47); SE, 86.0%; SP, 93.3%; positive predictive value
      (PPV), 99.1%; and negative predictive value (NPV), 43.1%. In a hypothetical
      screening setting (10,000 women; CIN2 prevalence, 1%), this marker combination
      should theoretically detect CIN2 with 86.0% SE, 100% SP, 99.1% PPV, and 99.6%
      NPV, area under ROC curve of 0.930 (95% CI, 0.909-0.951), and odds ratio, 29998.0
      (95% CI, 7,879.0-37,338.0). Combining 2 markers (LR67 and VEGF-C) enables
      accurate detection of high-grade CIN in a clinical setting. However, testing the
      performance of this marker combination in a screening setting necessitates their
      analysis in cytological samples.

PMID- 18317214
TI  - XXI. Erich Burghardt.

PMID- 18317215
TI  - Uterine adenolipoleiomyoma: a tumor with potential of aggressive behavior.
AB  - An unusual uterine adenolipoleiomyoma forming intramural and subserosal masses
      and recurring within 16 months in the form of huge coalescent uterine masses is
      described. Histology showed the mass to be composed of benign-appearing smooth
      muscle, mature adipose tissue, and bland endocervical-type glands. The recurrent
      adenolipoleiomyoma contained, in addition, benign-appearing endometrial-type
      glands and stroma and showed small foci of atypically proliferating endocervical
      type epithelium. This is the fourth report of adenolipoleiomyoma within the
      uterus, the second with an intramural location, and the first with an aggressive
      behavior in the form of massive local recurrence.

PMID- 18317216
TI  - Intraplacental choriocarcinoma arising in a second trimester placenta with
      partial hydatidiform mole.
AB  - We report a well-documented case of a 28-year-old woman, gravida 3, para 1,
      undergoing termination at 22 weeks for fetal congenital malformations with
      concurrent partial hydatidiform mole and choriocarcinoma. A fetal ultrasound
      showed spina bifida, and an elective termination was performed. One month later,
      the patient presented with vaginal bleeding, cough, and shortness of breath. A
      chest computed tomographic scan revealed multiple lung nodules. A pelvic
      ultrasound was consistent with retained products of conception, and endometrial
      sampling showed an atypical trophoblastic proliferation consistent with
      choriocarcinoma. The serum beta-human chorionic gonadotropin level was greater
      than 100,000 IU/mL. The placental pathology reviewed at our institution showed
      microscopic foci of choriocarcinoma arising in a partial hydatidiform mole. Flow
      cytometry performed on paraffin-embedded tissue showed a triploid peak, which
      confirmed the partial molar nature of this gestation. Immunohistochemistry showed
      nuclear p57 expression in the partial molar villous trophoblastic and stromal
      cells, but not in the severely atypical trophoblasts, further supporting the
      diagnosis of intraplacental choriocarcinoma distinct from the partial mole.
      Although the molecular pathogenesis remains to be elucidated, this report
      provides additional evidence that choriocarcinoma may arise directly from partial
      molar gestations. Moreover, it emphasizes the importance of thorough sampling of
      placentas with partial hydatidiform mole in search of minute foci of
      choriocarcinoma because they might represent a potential source of metastatic
      gestational trophoblastic disease.

PMID- 18317217
TI  - Primary extranodal marginal zone B-cell lymphoma of the female genital tract: a
      case report and literature review.
AB  - Primary extranodal marginal zone B-cell lymphoma (EMZL) of the female genital
      tract is a clinical indolent disease. A 61-year-old woman presenting with vaginal
      prolapse underwent a vaginal hysterectomy and anterior colporrhaphy. Histological
      examination of the uterus revealed lymphocytic infiltration of the endometrium.
      The immunohistochemical profile was not in accordance with any known reactive
      lymphocytic proliferation. Additional polymerase chain reaction and fluorescence
      in situ hybridization established the diagnosis of EMZL. After staging workup, it
      was classified as Ann-Arbor stage 1E. Therefore, no adjuvant therapy was needed.
      Incidental finding of EMZL in the endometrium is exceptional. The asymptomatic
      presentation is according to the indolent character of extranodal marginal zone
      lymphoma.

PMID- 18317218
TI  - Uterine neoplasms composed of rhabdoid cells do not exhibit loss of INI1
      immunoreactivity and are not related to childhood malignant rhabdoid tumor.
AB  - Malignant rhabdoid tumors are rare childhood neoplasms which occur most commonly
      in the kidneys, soft tissue, and central nervous system. They are characterized
      by cells with eccentric vesicular nuclei, prominent nucleoli, and abundant
      eosinophilic cytoplasm. Recently, it has been demonstrated that malignant
      rhabdoid tumors in childhood are characterized by biallelic deletion or mutation
      involving the SMARCB1/INI1 gene on chromosome 22. These molecular events result
      in loss of immunohistochemical expression of INI1. Neoplasms with a similar
      morphology occur in adults, either in pure form or associated with a parent
      tumor. It is controversial whether such neoplasms in adults are related to
      childhood malignant rhabdoid tumor or whether a rhabdoid morphology represents a
      nonspecific phenotype which can occur in a variety of neoplasms. In this study,
      we stained a series of adult uterine neoplasms with a prominent component of
      rhabdoid cells with the Baf 47 antibody which detects INI1; we aimed to ascertain
      whether these are related to childhood malignant rhabdoid tumor. Neoplasms
      included were an undifferentiated sarcoma consisting entirely of rhabdoid cells,
      2 carcinosarcomas with a mesenchymal component composed entirely of rhabdoid
      cells, and 3 uterine tumors resembling ovarian sex cord tumor with rhabdoid
      cells. In all cases, there was positive nuclear staining of the rhabdoid cells
      with Baf 47, suggesting an absence of gene deletion or mutation and that these
      neoplasms are not related to childhood malignant rhabdoid tumor. In adults, we
      suggest that a diagnosis of malignant rhabdoid tumor should not be made without
      genetic confirmation or loss of immunohistochemical expression of Baf 47. In the
      absence of these, an attempt should be made to classify such tumors on the basis
      of any associated parent neoplasm and/or immunohistochemical or ultrastructural
      evidence of specific differentiation. We reviewed uterine neoplasms with a
      rhabdoid phenotype.

PMID- 18317219
TI  - Uterine tumors resembling ovarian sex cord tumors: an update.
AB  - Tumors of the uterus resembling ovarian sex cord tumors were reported by Clement
      and Scully in 1976 and were divided in 2 groups: group 1, endometrial stromal
      tumors, and group 2, mural uterine tumors-both with elements resembling ovarian
      sex cord tumors. In the former, the sex cord component constitutes a minor
      portion of an endometrial stromal neoplasm, whereas in the latter, it is the
      predominant or exclusive component of a uterine wall lesion composed of a variety
      of mesenchymal elements. An origin from endometrial stromal cells, adenomyosis,
      stromal myosis, endometriosis, or multipotential cells within the myometrium was
      postulated in both groups of tumors. In group 1 tumors, the prognosis depends on
      the type, grade, and stage of the underlying stromal neoplasm. Group 2 tumors
      seemed to be benign, although because of the occasional recurrence of these
      tumors, they should be considered of low-grade malignant potential. In recent
      years, the histological features in group 2 were found to be much more varied
      than those in group 1 and consisted among others of retiform areas, glomeruloid
      structures, and Leydig-like cells. In group 1 tumors, the sex cord elements
      remained limited to cords, trabeculae, nests, and tubules. Eventually, the
      abbreviation ESTSCLE, or endometrial stromal tumors with sex cord-like elements,
      was given to group 1 tumors, whereas UTROSCT, or uterine tumor resembling ovarian
      sex cord tumor, was used for group 2 tumors. The most significant information in
      recently conducted studies concerns the immunophenotype of these lesions
      especially of UTROSCT. Out of the plethora of the immunohistochemical stains, a
      panel of 4 including calretinin, inhibin, CD99, and Melan A has emerged which
      seemed to be the most characteristic sex cord markers. Positivity for calretinin
      and at least for 1 of the other above-mentioned markers may thus confirm the
      diagnosis of UTROSCT. Endometrial stromal tumors with sex cord-like elements, on
      the other hand, usually express only 1 sex cord marker, mostly calretinin.
      However, additional studies are necessary to confirm these observations. In
      conclusion, UTROSCT and, to a lesser degree, ESTSCLE, are polyphenotypic
      neoplasms, which, according to the evidence available at present, most likely
      arise from pluripotential uterine mesenchymal cells. In UTROSCT, the
      differentiation into sex cord components is predominant or exclusive, whereas in
      ESTSCLE, it is minor.

PMID- 18317220
TI  - Krukenberg tumor with yolk sac tumor differentiation.
AB  - An unusual case of bilateral Krukenberg tumor with foci of yolk sac tumor (YST)
      differentiation occurring in a 50-year-old patient is reported. The primary tumor
      was in the gastric antrum, and it showed morphology of poorly differentiated
      adenocarcinoma with diffuse and solid growth pattern. A component of typical YST
      was not found in the gastric primary and lymph node metastases, although some
      cells in these locations were positive for alpha-fetoprotein. In the ovarian
      metastases, YST element showed microcystic/reticular and solid patterns, whereas
      the adenocarcinoma component was of diffuse type with signet ring cells and with
      some undifferentiated areas. The case represents further example of the somatic
      cell-derived tumor with focal germ cell-type differentiation and the first report
      of YST differentiation in Krukenberg tumor.

PMID- 18317221
TI  - Highly differentiated follicular carcinoma arising from struma ovarii: a report
      of 3 cases, a review of the literature, and a reassessment of so-called
      peritoneal strumosis.
AB  - Struma ovarii has elicited considerable interest because of its many unique
      features since Ludwig Pick first elucidated its relationship to teratoma in the
      early part of the 20th century. The most common thyroid-type malignancies to
      arise in struma ovarii are papillary and follicular carcinomas. In this article,
      we describe a newly recognized neoplasm originating from struma ovarii that we
      interpret as follicular carcinoma with a high degree of differentiation. By
      definition, all of these cases have an innocuous appearance resembling that of
      nonneoplastic thyroid tissue in both the ovary and sites of dissemination.
      Including our own, 14 cases in the literature spread to the peritoneum, and 4
      metastasized to more distant sites. The peritoneal involvement more often was
      diagnosed at the same time as the ovarian struma; however, the systemic
      dissemination occurred subsequent to oophorectomy. Our index patient with highly
      differentiated follicular carcinoma (HDFCO) developed peritoneal dissemination
      and para-aortic lymph node metastases 26 years after excision of ovarian struma.
      Vascular invasion was not identified in any of the cases; however, the primary
      neoplasm extended to the surface of the ovary in 2 cases with peritoneal
      involvement. Because of its harmless histological appearance, this form of
      follicular carcinoma characteristically cannot be diagnosed until the neoplasm
      spreads beyond the ovary, thus, showing evidence of aggressive behavior. The
      corollary of this observation is that cases having the histological appearance of
      ordinary struma ovarii can rarely behave in a malignant fashion. Although cases
      of typical thyroid-type carcinoma with extraovarian dissemination are relatively
      easy to diagnose, those with an innocuous histological appearance present
      nosological and diagnostic difficulties. The differential diagnosis of peritoneal
      dissemination of struma includes HDFCO, the typical types of thyroid cancer, and
      so-called strumosis. We have studied the relationship of HDFCO to cases reported
      as peritoneal strumosis or similar terms and doubt the existence of the latter as
      a distinct clinicopathologic entity. The treatment of choice for patients with
      HDFCO is local resection of the extraovarian tumor with subsequent thyroidectomy
      followed by radioactive iodine ablation.

PMID- 18317222
TI  - Taxol resistance among the different histological subtypes of ovarian cancer may
      be associated with the expression of class III beta-tubulin.
AB  - The prognostic significance of histology has been well established in epithelial
      ovarian cancer (EOC). Clear cell and mucinous histologies are especially
      generally accepted to result in an adverse outcome because of their poor
      chemotherapy response. Previous reports suggested that class III beta-tubulin
      induced taxol resistance in association with a reduced effect on microtubule
      dynamic instability. Thus, this study aimed to evaluate class III beta-tubulin
      expression and examine whether the protein level of class III beta-tubulin was
      correlated with the histological difference in chemosensitivity. Class III beta
      tubulin expression in EOC tissues (n = 80) was immunohistochemically scored into
      4 groups (-, +/-, +, ++). High-level (+, ++) class III beta-tubulin expression
      was detected in 30 of 35 clear cell carcinomas, in 8 of 10 mucinous carcinomas, 5
      of 11 endometrioid carcinomas, and 5 of 24 serous carcinomas. Nineteen patients
      were evaluable for response. In 5 responders, high-level class III beta-tubulin
      expression was not detected. On the other hand, it was detected in 10 of 14
      nonresponders. In some ovarian cancer cell lines, we evaluated class III beta
      tubulin expression by Western blot analysis. Class III beta-tubulin expression in
      nonserous carcinoma tended to be higher than that in serous carcinoma. Taxol
      resistant SKOV cells showed high-level class III beta-tubulin expression compared
      with wild-type SKOV cells. Taxol sensitivity differing among histological
      subtypes in EOC is associated with the expression of class III beta-tubulin.

PMID- 18317223
TI  - Immunohistochemical analysis of reserve cell-like cells of ovarian mullerian
      mucinous/mixed epithelial borderline tumor.
AB  - Ovarian mucinous borderline tumor of mullerian type (MMBT) and mixed epithelial
      borderline tumor of mullerian type (MEBT) are uncommon subtypes of ovarian
      surface epithelial tumors. Both are often associated with endometriosis, but
      their histogenesis is still debated. We have noticed occasional foci of
      subepithelial cuboidal cells resembling uterine cervical reserve cells (RCs) in
      MMBTs/MEBTs, which have not been documented in the literature to the best of our
      knowledge. This study was carried out to identify the presence of RC-like cells
      (RCLCs) in MMBTs/MEBTs and their immunohistochemical features in comparison to
      those of cervical RCs. We analyzed 10 consecutive cases of RC-like MMBTs/MEBTs, 6
      of which were associated with endometriosis. Immunohistochemistry was performed
      for p63, cytokeratin 34BE12, cytokeratin 17 (CK17), and low-molecular cytokeratin
      CAM5.2. In 9 of 10 cases, RCLCs were appreciated in hematoxylin-eosin stain,
      although their amount in the tumor varied from case to case.
      Immunohistochemically, RCLCs were positive for p63 in 9 cases. They were positive
      for both 34BE12 and CK17 and were very weakly positive or negative for CAM5.2 in
      8 cases. This immunohistochemical profile is similar to that seen in the cervical
      RCs. Reserve cell-like cells were also found in the foci of endometriosis
      coexisting with MMBTs/MEBTs in 1 of 5 cases examined. We draw attention to the
      existence of the RCLCs in MMBTs/MEBTs and in endometriosis. Their similarity to
      the cervical RCs may indicate their potential role as precursor cell that may
      subsequently differentiate into different mullerian cell types, thus merit
      further study.

PMID- 18317224
TI  - The prognostic and predictive value of syntactic structure analysis in serous
      carcinoma of the ovary.
AB  - The objective of this study was to determine whether syntactic structure analysis
      (SSA) can predict survival outcome and chemotherapeutic response in ovarian
      carcinoma. Syntactic structure analysis parameters, blindly determined in
      archived hematoxylin and eosin sections of 132, International Federation of
      Gynecology and Obstetrics (FIGO) stage I to IV serous ovarian tumors, and
      clinicopathologic parameters were evaluated as to their univariate and
      multivariate prognostic value and ability to predict chemotherapy response as
      measured by changes in CA125 levels. Univariate analysis revealed FIGO stage,
      tumor grade, preoperative CA125, presence of ascites, extent of disease residuum,
      and the SSA parameters minimum spanning tree (min MST), maximum MST (max MST),
      percent connectivity to 1, and 2 nearest neighbors to be significant predictors
      of overall survival and disease-free survival. Tumor grade, FIGO stage, extent of
      disease residuum, presence of ascites, and percent connectivity to 2 nearest
      neighbors were found to be significant predictors of chemotherapy response.
      Multivariate analysis revealed extent of disease residuum to be a significant
      predictor for overall survival (P <or= 0.01) and prediction of chemotherapy
      response (P = 0.05). International Federation of Gynecology and Obstetrics stage
      was a significant predictor for disease-free survival (P <or= 0.01). Syntactic
      structure analysis parameters did not retain independent significance. Syntactic
      structure analysis features can predict survival outcome and chemotherapy
      response in ovarian carcinoma but, with multivariate analysis, are overshadowed
      by FIGO stage and residual disease.

PMID- 18317225
TI  - Women with undiagnosed colorectal adenocarcinomas presenting with ovarian
      metastases: clinicopathologic features and comparison with women having known
      colorectal adenocarcinomas and ovarian involvement.
AB  - Recognition of an ovarian tumor as a metastasis from an undiagnosed primary
      gastrointestinal tract carcinoma can be difficult when specific symptoms
      referable to the primary tumor are lacking and the tumor simulates a primary
      ovarian neoplasm grossly and microscopically. Ovarian metastases of colorectal
      adenocarcinomas, in particular, continue to pose diagnostic challenges both
      clinically and pathologically. Clinicopathologic features of 20 cases of ovarian
      metastases from undiagnosed colorectal adenocarcinomas (U-CRAs) were compared
      with those of 22 cases having metastases from known colorectal adenocarcinomas (K
      CRAs). Women with ovarian metastases from U-CRAs were significantly younger (mean
      age, 48 years; median, 47 years) than those with ovarian metastases from K-CRAs
      (mean, 61 years; median, 63 years) (P = 0.002), presented with clinical findings
      related to the ovarian metastases, often had elevated CA-125 levels, and lacked
      specific symptoms due to the colorectal carcinomas, which were diagnosed only at
      the time of intraoperative evaluation of the ovarian tumors. Mean/median ovarian
      tumor sizes (12.8/13.0 cm for U-CRAs; 14.1/15.8 cm for K-CRAs) and frequencies of
      bilaterality (45% for U-CRAs and 36% for K-CRAs) were not significantly different
      for the 2 groups; frequencies of clinically unilateral tumors of more than 10 cm
      were similar in both groups (30% for U-CRAs and 45% for KCRAs). Other features
      more commonly observed in ovarian metastases from U-CRAs included mucinous
      differentiation, extracellular mucin production, and some degree of cytokeratin 7
      expression; endometrioid-like differentiation was more common in metastases from
      K-CRA, but a garland pattern of necrosis and the presence of a confluent
      glandular, rather than infiltrative, pattern of invasion were similarly common in
      both groups. In cases having ovarian metastases from U-CRA, the younger age of
      the women, uniform presentation as pelvic masses without symptoms referable to
      the bowel, elevated CA-125 levels, occasional presentation as a large clinically
      unilateral tumor, frequent mucinous differentiation, and frequent coexpression of
      cytokeratin 7 are features that can contribute to misclassification of these
      metastases as primary ovarian neoplasms.

PMID- 18317226
TI  - Grading of ovarian cancer: a histotype-specific approach.
AB  - Over the last decade, our understanding of ovarian cancer has evolved; it is no
      longer considered a single entity, but instead a heterogeneous group of tumors.
      Accordingly, a histotype-specific grading system seems to be more appropriate
      than a universal grading system to reflect the diversity of this disease. In this
      article, this histotype-specific approach to the grading of ovarian carcinoma is
      discussed.

PMID- 18317227
TI  - Histologic subtypes of ovarian carcinoma: an overview.
AB  - Reproducible subclassification of ovarian carcinomas is biologically and
      increasingly therapeutically important. The traditional morphologic approach that
      ignores genotype and immunophenotype is subjective and therefore suboptimal. This
      review covers the prevalence, morphology, immunophenotype and, in some cases,
      genotype of each major ovarian cancer subtype. Serous carcinomas, frequently WT1
      positive, are morphologically diverse and mimic other tumors. Most transitional
      cell carcinomas are closely related to them. Mucinous carcinomas are uncommon and
      should only be diagnosed after extraovarian primaries are excluded; true ovarian
      mucinous carcinomas are usually low stage. Intestinal and mullerian mucinous
      (seromucinous) tumors are histogenetically and clinically distinct. Ovarian
      endometrioid carcinomas almost always resemble endometrioid carcinomas of
      endometrium, express estrogen receptors (ER) but not WT1, and are frequently low
      grade and low stage. Ovarian clear cell carcinomas, negative for ER and WT1 and
      lacking p53 overexpression, have a limited morphologic repertoire and are
      frequently low stage at presentation. Clinical biology, immunohistochemistry, and
      genotype can be used to enhance diagnostic objectivity.

PMID- 18317229
TI  - Estimating vertically acquired HIV infections and the impact of the prevention of
      mother-to-child transmission program in Zimbabwe: insights from decision analysis
      models.
AB  - BACKGROUND: The World Health Organization recommends a single-dose nevirapine
      (NVP) regimen for prevention of mother-to-child transmission (PMTCT) of HIV in
      settings without the capacity to deliver more complex regimens, but the
      population-level impact of this intervention has rarely been assessed. METHODS: A
      decision analysis model was developed, parameterized, and applied using local
      epidemiologic and demographic data to estimate vertical transmission of HIV and
      the impact of the PMTCT program in Zimbabwe up to 2005. RESULTS: Between 1980 and
      2005, of approximately 10 million children born in Zimbabwe, a cumulative 504,000
      (range: 362,000 to 665,000) were vertically infected with HIV; 59% of these
      infections occurred in nonurban areas. Mother-to-child transmission (MTCT) of HIV
      decreased from 8.2% (range: 6.0% to 10.7%) in 2000 to 6.2% (range: 4.9% to 8.9%)
      in 2005, predominantly attributable to declining maternal HIV prevalence rather
      than to the PMTCT program. Between 2002 and 2005, the single-dose NVP PMTCT
      program may have averted 4600 (range: 3900 to 7800) infections. In 2005, 32%
      (range: 26% to 44%) and 4.0% (range: 2.7% to 6.2%) of infections were
      attributable to breast-feeding and maternal seroconversion, respectively, and the
      PMTCT program reduced infant infections by 8.8% (range: 5.5% to 12.1%). Twice as
      many infections could have been averted had a more efficacious but logistically
      more complex NVP + zidovudine regimen been implemented with similar coverage
      (50%) and acceptance (42%). DISCUSSION: The decline in MTCT from 2000 to 2005 is
      attributable more to the concurrent decrease in HIV prevalence in pregnant women
      than to PMTCT at the current level of rollout. To improve the impact of PMTCT,
      program coverage and acceptance must be increased, especially in rural areas, and
      local infrastructure must then be strengthened so that single-dose NVP can be
      replaced with a more efficacious regimen.

PMID- 18317228
TI  - Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and
      their clinical implications.
AB  - The accepted view of ovarian carcinogenesis is that carcinoma begins in the
      ovary, undergoes progressive "dedifferentiation" from a well to a poorly
      differentiated tumor, and then spreads to the pelvic and abdominal cavities
      before metastasizing to distant sites. It has therefore been reasoned that
      survival for this highly lethal disease could be improved by developing screening
      methods that detect disease when it is confined to the ovary. To date, however,
      no prospective randomized trial of any ovarian cancer screening test(s) has
      demonstrated a decrease in mortality. We believe that one of the main reasons for
      this is that the dogma underlying ovarian carcinogenesis is flawed. Based on
      studies performed in our laboratory during the last decade, we have proposed a
      model of ovarian carcinogenesis that takes into account the diverse nature of
      ovarian cancer and correlates the clinical, pathological, and molecular features
      of the disease. In this model, ovarian tumors are divided into 2 groups
      designated type I and type II. Type I tumors are slow growing, generally confined
      to the ovary at diagnosis, and develop from well-established precursor lesions
      that are termed "borderline" tumors. Type I tumors include low-grade
      micropapillary serous carcinoma, mucinous, endometrioid, and clear cell
      carcinomas. They are genetically stable and are characterized by mutations in a
      number of different genes including KRAS, BRAF, PTEN, and beta-catenin. Type II
      tumors are rapidly growing highly aggressive neoplasms for which well-defined
      precursor lesions have not been described. Type II tumors include high-grade
      serous carcinoma, malignant mixed mesodermal tumors (carcinosarcomas), and
      undifferentiated carcinomas. This group of tumors has a high level of genetic
      instability and is characterized by mutation of TP53. The model helps to explain
      why current screening techniques, aimed at detecting stage I disease, have not
      been effective. Tumors that remain confined to the ovary for a long period belong
      to the type I group, but they account for only 25% of the malignant tumors. Most
      of what is considered ovarian cancer belongs to the type II category, and these
      are only rarely confined to the ovary. Although the reasons for this are not
      entirely clear, possible explanations include rapid spread from the ovary early
      in carcinogenesis and development of carcinoma in extra ovarian sites, notably,
      the peritoneum and fallopian tube, with secondary involvement of the ovary. The
      latter tumors are advanced stage at their inception. Therefore, a more realistic
      end point for the early detection of ovarian cancer is volume and not stage of
      disease. The model does not replace the histopathologic classification but, by
      drawing attention to the molecular genetic events that play a role in tumor
      progression, sheds light on new approaches to early detection and treatment.

PMID- 18317230
TI  - National survey of prevalent HIV strains: limited genetic variation of Korean HIV
      1 clade B within the population of Korean men who have sex with men.
AB  - The evolution of HIV is the result of an explosive combination of factors-a high
      rate of mutation, replication dynamics, frequent recombination, and natural
      selection. To understand the evolution of the distinctive Korean HIV-1 B clade,
      we investigated the characteristics of the genetic variation of the HIV-1 subtype
      B env gene within the group of Korean men who have sex with men (MSM). From 1985
      to 2005, 700 HIV-1-infected Koreans were sequenced at the V1 to V5 region of the
      HIV-1 env gene. In the phylogenetic analysis, 560 isolates were identified as HIV
      1 subtype B, and 489 of the 560 isolates were HIV-1 Korean clade B. Based on
      epidemiologic investigation, 249 of 700 HIV-1-infected patients were HIV-1
      subtype B-infected MSM. Interestingly, the proportion of the GPGS motif in MSM
      infected by Koreans was 1.6 times higher than in MSM infected by foreigners, and
      the genetic expansions of diversity and divergence for HIV-1 subtype B in Korean
      MSM were 2.1% and 2.5%, respectively. This was much lower than those observed in
      other countries. Therefore, our findings imply that the HIV strains in this group
      were closely related. This result may be helpful for understanding the evolution
      of the distinct HIV-1 Korean B clade.

PMID- 18317231
TI  - Postmenstrual age and CYP2D6 polymorphisms determine tramadol o-demethylation in
      critically ill neonates and infants.
AB  - To document determinants of O-demethylation in critically ill (pre)term neonates
      and infants, tramadol (M) and O-demethyl tramadol (M1) concentrations were
      quantified in eighty-six 24 h urine collections and 168 plasma samples. A
      significant correlation of urine log M/M1 (0.98, SD 0.66) and plasma log M/M1
      (0.78, SD 0.45) with postmenstrual age (PMA) (r = -0.69 and -0.65) was observed.
      One-way analysis of variance documented a significant decrease in urine log and
      plasma log M/M1 with increasing CYP2D6 activity score (F value 11.6 and 22.55).
      PMA and CYP2D6 activity score determined the urine and plasma log M/M1 (R 0.59
      and 0.64) in a forward multiple regression model. We therefore conclude that PMA
      and CYP2D6 polymorphisms determined O-demethylation activity in (pre)term
      neonates and young infants, illustrating the impact of pharmacogenetics on drug
      metabolism in neonates although a relevant part of the interindividual
      varaibility remained unexplained. Besides compound-specific relevance, CYP2D6 iso
      enzyme specific data on in vivo ontogeny of O-demethylation can contribute to
      safer and more effective administration of drugs metabolized by the same route in
      this population.

PMID- 18317232
TI  - Carnitine supplementation induces acylcarnitine production in tissues of very
      long-chain acyl-CoA dehydrogenase-deficient mice, without replenishing low free
      carnitine.
AB  - Deficiency of very long-chain acyl-CoA dehydrogenase (VLCAD) results in
      accumulation of C14-C18 acylcarnitines and low free carnitine. Carnitine
      supplementation is still controversial. VLCAD knockout (VLCAD(+/-)) mice exhibit
      a similar clinical and biochemical phenotype to those observed in humans.
      VLCAD(+/-) mice were fed with carnitine dissolved in drinking water. Carnitine,
      acylcarnitines, and gamma-butyrobetaine were measured in blood and tissues.
      Measurements were performed under resting conditions, after exercise and after 24
      h of regeneration. HepG2 cells were incubated with palmitoyl-CoA and palmitoyl
      carnitine, respectively, to examine toxicity. With carnitine supplementation,
      acylcarnitine production was significantly induced. Nevertheless, carnitine was
      low in skeletal muscle after exercise. Without carnitine supplementation, liver
      carnitine significantly increased after exercise, and after 24 h of regeneration,
      carnitine concentrations in skeletal muscle completely replenished to initial
      values. Incubation of hepatic cells with palmitoyl-CoA and palmitoyl-carnitine
      revealed a significantly reduced cell viability after incubation with palmitoyl
      carnitine. The present study demonstrates that carnitine supplementation results
      in significant accumulation of potentially toxic acylcarnitines in tissues. The
      expected prevention of low tissue carnitine was not confirmed. The principle
      mechanism regulating carnitine homeostasis seems to be endogenous carnitine
      biosynthesis, also under conditions with increased demand of carnitine such as in
      VLCAD-deficiency.

PMID- 18317233
TI  - Evidence of increased bone resorption in neurofibromatosis type 1 using urinary
      pyridinium crosslink analysis.
AB  - Although neurofibromatosis type 1 (NF1) is a neurocutaneous disorder, skeletal
      abnormalities such as long-bone dysplasia, scoliosis, sphenoid wing dysplasia,
      and osteopenia are observed. To investigate the role of bone resorption as a
      mechanism for the bony abnormalities, we selected urinary pyridinium crosslinks
      (collagen degradation products excreted in urine) as a measure of bone resorption
      in NF1. Bone resorption was evaluated by quantitative assessment of the urinary
      excretion of pyridinium crosslinks [pyridinoline (Pyd) and deoxypyridinoline
      (Dpd)]. Total (free plus peptide-bound) pyridinium crosslinks from the first
      morning urines from 59 NF1 children (ages 5-19) were extracted and analyzed (17
      children with a localized skeletal dysplasia, and 42 without). The data were
      compared with a healthy reference population without NF1 (n = 99). Multivariate
      analyses, controlling for age showed statistically significant increases for Dpd
      (p < 0.001) and the Dpd/Pyd ratio (p < 0.001) in NF1 individuals with and without
      a skeletal dysplasia. NF1 children have an increase in the urinary excretion of
      pyridinium crosslinks, reflecting increased bone resorption. The effects of NF1
      haploinsufficiency likely contribute to abnormal bone remodeling, either directly
      or indirectly by aberrant Ras signaling, potentially predisposing NF1 individuals
      to localized skeletal defects.

PMID- 18317234
TI  - Activation of the granzyme pathway in children with severe respiratory syncytial
      virus infection.
AB  - Granzymes (Grs), serine proteases present in granules of effector lymphocytes,
      are involved in several host immune responses, including the activation of cell
      death and inflammatory pathways. The main goal of this study was to determine
      whether the local cell-mediated Gr pathway is activated during severe respiratory
      syncytial virus (RSV) lower respiratory tract illness (LRTI) in children.
      Tracheal aspirates (TA) from 23 children with RSV-LRTI and 12 controls without
      pulmonary disease were analyzed for Gr A and B. Bronchoalveolar lavage fluid
      samples from seven children with RSV-LRTI were analyzed for cellular expression
      of GrB. Levels of GrA and GrB in TA were significantly increased in RSV patients
      compared with controls and both Grs showed preserved activity. Gr levels
      correlated with the total leukocyte counts and IL-8 levels in the airways at
      several time points. However, no correlation between Gr levels and release of
      caspase-cleaved cytokeratin-18 was found. There was evidence for marked
      expression of GrB by both CD8(+) and CD4(+) T cells and natural killer cells in
      the respiratory tract. These findings suggest activation of the cell-mediated Gr
      pathway during severe RSV-LRTI in children.

PMID- 18317235
TI  - CLN3p impacts galactosylceramide transport, raft morphology, and lipid content.
AB  - Juvenile neuronal ceroid lipofuscinosis (JNCL) belongs to the neuronal ceroid
      lipofuscinoses characterized by blindness/seizures/motor/cognitive decline and
      early death. JNCL is caused by CLN3 gene mutations that negatively modulate cell
      growth/apoptosis. CLN3 protein (CLN3p) localizes to Golgi/Rab4-/Rab11-positive
      endosomes and lipid rafts, and harbors a galactosylceramide (GalCer) lipid raft
      binding domain. Goals are proving CLN3p participates in GalCer transport from
      Golgi to rafts, and GalCer deficits negatively affect cell growth/apoptosis.
      GalCer/mutant CLN3p are retained in Golgi, with CLN3p rescuing GalCer deficits in
      rafts. Diminishing GalCer in normal cells by GalCer synthase siRNA negatively
      affects cell growth/apoptosis. GalCer restores JNCL cell growth. WT CLN3p binds
      GalCer, but not mutant CLN3p. Sphingolipid content of rafts/Golgi is perturbed
      with diminished GalCer in rafts and accumulation in Golgi. CLN3-deficient raft
      vesicular structures are small by transmission electron microscopy, reflecting
      altered sphingolipid composition of rafts. CLN1/CLN2/CLN6 proteins bind to
      lysophosphatidic acid/sulfatide, CLN6/CLN8 proteins to GalCer, and CLN8 protein
      to ceramide. Sphingolipid composition/morphology of CLN1-/CLN2-/CLN6-/CLN8- and
      CLN9-deficient rafts are altered suggesting changes in raft structure/lipid
      stoichiometry could be common themes underlying these diseases.

PMID- 18317236
TI  - The role of mannose-binding lectin in susceptibility to infection in preterm
      neonates.
AB  - Preterm neonates are susceptible to infection due to a combination of sub-optimal
      immunity and increased exposure to invasive organisms. Mannose-binding lectin
      (MBL) is a component of the innate immune system, which may be especially
      important in the neonatal setting. The objective of this study was to investigate
      the impact of MBL on susceptibility and severity of infection in preterm neonates
      during their first month of life. One hundred fifty eight preterm neonates were
      genotyped for MBL mutations by heteroduplex analyses. Consecutive serum MBL
      levels were measured by ELISA and clinical and laboratory data, including blood
      cultures, were collected for each baby. A third of the premature neonates had
      genetically determined MBL deficiency. In addition, MBL levels were also low in
      the first week of life and lower in neonates with a wild type genotype who were
      less than 28 wk gestation or a birth weight of less than 1000 g, thereby
      increasing the number of neonates with a low MBL level at birth. MBL deficiency
      was associated with an increased risk of sepsis (p < 0.01). This study indicates
      that MBL levels are low in neonates at birth and renders premature neonates to an
      increased risk of infection.

PMID- 18317238
TI  - Modifiable maternal exposures and offspring blood pressure: a review of
      epidemiological studies of maternal age, diet, and smoking.
AB  - Prenatal programming of adult disease is well established in animals. In humans
      the impact of common in utero exposures on long-term offspring health is less
      clear. We reviewed epidemiology studies of modifiable maternal exposures and
      offspring blood pressure (BP). Three maternal exposures were identified for
      review and meta-analyzed where possible: smoking during pregnancy, diet, and age
      at childbirth. Meta-analysis suggested there was a modest association between
      higher offspring BP and prenatal exposure to smoke (confounder-adjusted beta =
      0.62 mm Hg, 95% confidence interval: 0.19-1.05, I = 16.4%). However, the level of
      confounder adjustment varied between studies, which in some studies attenuated
      the association to the null. There was no strong evidence that any component of
      maternal diet during pregnancy (maternal protein, energy, calcium, and various
      other nutrients) influences offspring BP. The results of studies of maternal age
      varied and there was strong evidence of heterogeneity in the pooled analysis. The
      association with maternal age, if present, was modest (confounder-adjusted beta =
      0.09 mm Hg/y, 95% confidence interval: -0.03 to 0.21, I = 89.8%). In sum, there
      is little empirical evidence that the maternal exposures reviewed program
      offspring BP. Other components of offspring health may be more susceptible to
      effects of programming in utero.

PMID- 18317237
TI  - Population and disease-based prevalence of the common mutations associated with
      surfactant deficiency.
AB  - The prevalence of the common mutations in the surfactant protein-B (121ins2),
      surfactant protein-C (I73T), and ATP-binding cassette member A3 (E292V) genes in
      population-based or case-control cohorts of newborn respiratory distress syndrome
      (RDS) is unknown. We determined the frequencies of these mutations in ethnically
      diverse population and disease-based cohorts using restriction enzyme analysis
      (121ins2 and E292V) and a 5' nuclease assay (I73T) in DNA samples from population
      based cohorts in Missouri, Norway, South Korea, and South Africa, and from a case
      control cohort of newborns with and without RDS (n = 420). We resequenced the ATP
      binding cassette member A3 gene (ABCA3) in E292V carriers and computationally
      inferred ABCA3 haplotypes. The population-based frequencies of 121ins2, E292V,
      and I73T were rare (<0.4%). E292V was present in 3.8% of newborns with RDS, a 10
      fold greater prevalence than in the Missouri cohort (p < 0.001). We did not
      identify other loss of function mutations in ABCA3 among patients with E292V that
      would account for their RDS. E292V occurred on a unique haplotype that was
      derived from a recombination of two common ABCA3 haplotypes. E292V was over
      represented in newborns with RDS suggesting that E292V or its unique haplotype
      impart increased genetic risk for RDS.

PMID- 18317239
TI  - Plasma biomarkers in pediatric patients undergoing cardiopulmonary bypass.
AB  - It is critical to identify at-risk patients and minimize the deleterious effects
      of cardiopulmonary bypass (CPB) procedures in pediatric populations. The present
      study screened the plasma proteome of pediatric patients undergoing CPB
      procedures to identify potential clinical biomarkers related to tissue damage,
      inflammation, or other pathologies. Blood samples were collected at five
      different time points from 10 children undergoing a CPB procedure. Plasma was
      isolated and analyzed using two-dimensional differential in-gel electrophoresis
      and matrix-assisted laser desorption ionization time of flight mass spectrometry.
      Levels of differentially regulated proteins identified by two-dimensional
      differential in-gel electrophoresis, and related proteins were then measured in
      all time points and patients. As well, associated small molecules and ions were
      measured. The present study identified 13 proteins and protein isoforms altered
      in expression, including hemopexin, ceruloplasmin, inter-alpha inhibitor H4, and
      alpha-2-macroglobulin. Immunoblot analysis revealed significant decreases in each
      of these proteins during the CPB procedure. Significant changes in the levels of
      copper, iron, Hb, epinephrine, norepinephrine, and serotonin were observed. The
      potential markers of pathology (inflammation, oxidative stress) identified during
      this preliminary study may illuminate opportunities for preventative measures
      and/or treatments during and following CPB procedures in pediatric patients.

PMID- 18317240
TI  - Alzheimer disease research: have we forgotten the cerebrovascular circulation?

PMID- 18317241
TI  - The inflammatory hypothesis of Alzheimer disease: dead or alive?

PMID- 18317243
TI  - A randomized, double-blind, placebo controlled-trial of triflusal in mild
      cognitive impairment: the TRIMCI study.
AB  - BACKGROUND: Amnestic mild cognitive impairment represents, in many cases, the
      earliest clinical phases of Alzheimer disease. Anti-inflammatory agents have
      epidemiologic support as drugs potentially beneficial in Alzheimer disease. In
      vivo studies have shown that Triflusal and its active metabolite 2-hydroxy-4
      trifluoromethyl-benzoic acid have potent anti-inflammatory actions in the central
      nervous system. METHODS: We conducted a randomized, double-blind, placebo
      controlled trial of Triflusal in patients with amnestic mild cognitive
      impairment. Subjects were randomly assigned to receive 900 mg of Triflusal or
      placebo for 18 months. The primary outcome was a change in Cognitive subscale of
      the Alzheimer Disease Assessment Scale; conversion to dementia was a secondary
      outcome. RESULTS: A slow rate of recruitment forced a premature cessation of the
      study. Two hundred and fifty-seven subjects were enrolled and followed-up for an
      average of 13 months. The significance level was not reached for the primary
      outcome even though a trend in favor of Triflusal was observed. However, there
      was a significant difference in the probability of progression to dementia of
      Alzheimer's type with a lower risk in the Triflusal compared with the placebo
      group (hazard ratio, 2.10; 95% confidence interval, 1.10-4.01; P=0.024).
      CONCLUSIONS: In this study, Triflusal therapy was associated with a significant
      lower rate of conversion to dementia that is likely to be clinically relevant.
      Because the trial was prematurely halted, these results should be interpreted
      with caution and require further confirmation.

PMID- 18317244
TI  - Effects of galantamine on measures of attention: results from 2 clinical trials
      in Alzheimer disease patients with comparisons to donepezil.
AB  - Deficits in attention are present early in the course of Alzheimer disease (AD).
      Acetylcholine receptors are appealing molecular targets for intervention as
      cholinergic pathways are involved in the neurobiology of attention. For this
      reason, measures of attention were included in 2 independent, multicenter,
      randomized, parallel, controlled trials in subjects with AD comparing the effects
      of galantamine, an acetylcholinesterase inhibitor and postulated nicotinic
      receptor modulator, and donepezil, an acetylcholinesterase inhibitor. The
      attention battery of the Cognitive Drug Research computerized assessment system
      was used in both trials. Small magnitude, positive signals were observed for
      simple and choice reaction times for both compounds. Attention task performance
      tended to improve early for galantamine-treated subjects. A consistent temporal
      pattern of improvement was not observed in donepezil-treated subjects.
      Quantitative findings appeared more pronounced in subjects with moderate AD.
      Galantamine's proposed action as a nicotinic receptor modulator may bear on these
      findings. Improved attention may have positive effects on cognitive and
      functional outcomes for AD patients, although this hypothesis requires further
      study and validation.

PMID- 18317242
TI  - Children of persons with Alzheimer disease: what does the future hold?
AB  - Children of persons with Alzheimer disease (AD), as a group, face an increased
      risk of developing AD. Many of them, throughout their adult lives, seek input on
      how to reduce their chances of one day suffering their parent's fate. We examine
      the state of knowledge with respect to risk and protective factors for AD and
      recommend a research agenda with special emphasis on AD offspring.

PMID- 18317245
TI  - Cardiorespiratory fitness in early-stage Alzheimer disease.
AB  - There is an increasing interest in exercise and fitness in Alzheimer disease (AD)
      given evidence suggesting a role in the maintenance of cognitive health. There
      is, however, little data on the objective measure of cardiorespiratory fitness in
      individuals with AD. Thus, we assessed cardiorespiratory fitness in early AD and
      its relationship with physical activity levels, health markers, and cognitive
      performance in nondemented (Clinical Dementia Rating 0, n=31) and early-stage AD
      (Clinical Dementia Rating 0.5 and 1, n=31) participants. Cardiorespiratory
      fitness was assessed with maximal exercise testing to determine peak oxygen
      consumption (VOpeak2). Additionally, dual emission x-ray absorptiometry scanning
      for body composition and glucose tolerance tests were conducted. Despite
      reductions in physical performance and habitual physical activity levels in early
      AD, cardiorespiratory fitness (VOpeak2) was comparable in the 2 groups (19.8 in
      early AD vs. 21.2 mL/kg/min in nondemented, P=0.26). AD participants performed
      well on treadmill tests with similar levels of perceived exertion, maximal heart
      rate, and respiratory exchange ratio compared with nondemented individuals. After
      controlling for age and sex, VOpeak2 was associated with a beneficial
      glucoregulatory profile and inversely associated with percent body fat, body mass
      index, and triglycerides. A relationship between cognitive performance measures
      and VOpeak2 was not apparent. These results suggest that individuals in the early
      stages of AD have the capacity for maximal exercise testing and have comparable
      levels of cardiorespiratory fitness as nondemented individuals. Reduced physical
      activity associated with early AD underscores the need for further defining the
      role of exercise as a potential therapeutic intervention in the early stages of
      AD.

PMID- 18317246
TI  - Diagnostic value of CSF biomarker profile in frontotemporal lobar degeneration.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) biomarkers have been increasingly studied
      in dementia clinical and differential diagnosis. METHODS: We assessed levels of
      total tau protein (tauT), tau phosphorylated at threonine 181 (tau P-181), and
      beta-amyloid1-42 (A beta 42) in 34 patients with frontotemporal lobar
      degeneration (FTLD), 76 Alzheimer disease (AD) cases, and 93 controls (CTRL).
      Double sandwich enzyme-linked immunosorbent assays (Innogenetics) were used for
      measurements. RESULTS: Total tau was significantly increased and A beta 42
      decreased in FTLD and AD patients as compared with CTRL. CSF tau P-181 levels
      were significantly increased only in AD. The tauT/A beta 42 ratio successfully
      discriminated FTLD from CTRL with a 86.7% specificity and 80.6% sensitivity,
      whereas the tauT alone was more specific (95.7%) but less sensitive (64.75%). For
      the discrimination of FTLD from AD, tauT/A beta 42 ratio was better (90.3%
      sensitivity and 64.5% specificity) compared with the other biomarkers alone or in
      combination, whereas tau P-181 was less sensitive but more specific (68.4% and
      85.7%, respectively). Subtype analysis revealed that the most AD-like profile of
      biomarkers were observed in FTLD with motor neuron signs, whereas the most non-AD
      profile were observed in patients with primary progressive aphasia. CONCLUSIONS:
      Combined analysis of CSF biomarkers may be useful for the best possible
      antemortem discrimination of FTLD from AD.

PMID- 18317247
TI  - Brain N-acetylaspartate is reduced in Parkinson disease with dementia.
AB  - Persons with Parkinson disease (PD) are at risk of developing dementia. Of the
      dementias affecting patients with PD, PD with dementia (PDD) is not well
      understood, although brain imaging studies to date have observed characteristic
      patterns of brain atrophy. Metabolic differences have been observed in magnetic
      resonance spectroscopy (MRS) studies comparing patients with PDD to nondemented
      PD patients, although it is unclear whether PDD patients have abnormally low MRS
      ratios compared with healthy age-matched adults. In this study, 12 patients with
      PDD, 12 patients with PD and no dementia, and 12 age-matched healthy older adults
      underwent MRS of the posterior cingulate gyrus. Patients with PDD showed lower N
      acetylaspartate/creatine (NAA/Cr) compared with controls (P=0.004) and compared
      with nondemented PD patients (P=0.003). No abnormalities were observed in
      choline/Cr or myo-Inositol/Cr. NAA/Cr was correlated with mental status in
      patients with PD and in patients with PDD (r=0.56; P=0.029). The findings suggest
      that reduced NAA/Cr of the posterior cingulate could be used as a marker for
      dementia in patients with PD. Future studies investigating the utility of brain
      MRS as a predictor of dementia in PD and comparing brain metabolism in PDD with
      other dementias seem warranted.

PMID- 18317248
TI  - Polymorphisms of APOE and LRP genes in Brazilian individuals with Alzheimer
      disease.
AB  - Alzheimer disease (AD) is the most frequent cause of dementia in Western
      countries. Putative genetic risk factors for AD are polymorphisms in the
      apolipoprotein E (APOE) gene and in the low-density lipoprotein receptor-related
      protein (LRP) gene. Our objective was to investigate the role of the APOE coding
      region polymorphisms epsilon 2, epsilon 3, and epsilon 4 and APOE promoter
      variants A/T at position -491 and G/T at -219, as well as LRP polymorphism C/T,
      as risk factors for AD in Brazilian individuals. One hundred and twenty patients
      with probable AD, along with 120 controls were analyzed. A significant difference
      between patients and controls for epsilon 4 alleles was observed: frequency of
      this allele in AD was 0.31, and 0.10 in controls. Individuals with 2 epsilon 4
      alleles had a higher risk for AD than subjects with only 1 such allele; presence
      of 1 epsilon 2 allele proved protective. The presence of the T allele of the -219
      polymorphism was also associated with an increased risk of AD, but this
      polymorphism is in linkage disequilibrium with APOE epsilon polymorphisms. No
      significant differences between patients and controls were observed for -491 APOE
      or LRP polymorphisms. In this Brazilian population, both the epsilon 4 allele and
      T -219 polymorphism were associated with an increased risk for AD.

PMID- 18317249
TI  - Nutritional status is associated with disease progression in very mild Alzheimer
      disease.
AB  - The objective of this study is to identify, in a sample of very mild Alzheimer
      disease (AD) patients, factors associated with disease progression. The authors
      followed 160 AD patients from a multicenter cohort with a Clinical Dementia
      Rating (CDR) of 0.5, corresponding to very mild AD but with impairment
      insufficient to be classified as dementia. Patients with disease progression were
      defined as those with CDR> or =1 at 1 year; those with no progression (stable)
      remained at CDR 0.5. The baseline characteristics of these 2 groups of patients
      were compared in search of predictors of progression. After a 1-year follow-up,
      84 (52.5%) of the patients remained stable, CDR 0.5; 76 (47.5%) progressed to a
      CDR score > or =1. A baseline lower nutritional status assessed by the Mini
      Nutritional Assessment [odds ratio 0.80, 95% confidence interval (0.68-0.94),
      P=0.007] and a lower cognitive performance on the Alzheimer Disease Assessment
      Scale [odds ratio 1.22, 95% confidence interval (1.07-1.39), P=0.003] were found
      as predictors of progression. The results suggest that clinical assessment of
      nutritional status, along with cognitive data, may help detect patients at risk
      of progression in very early AD. Nutritional assessment should therefore form
      part of clinical evaluation of patients with AD at an early stage of the disease.

PMID- 18317250
TI  - Applicability of the abbreviated neuropsychologic battery (NEUROPSI) in Alzheimer
      disease patients.
AB  - NEUROPSI is a brief neuropsychologic battery developed to briefly assess a wide
      spectrum of cognitive functions. The aim of this study was to examine the
      applicability of a Portuguese version of this battery and verify the efficacy in
      detecting cognitive impairment in Alzheimer disease (AD) patients. NEUROPSI was
      applied to 75 elderly people, 25 patients with probable AD in mild stage (AD1),
      25 patients in moderate stage (AD2), and 25 healthy elderly persons (control
      group), matched with the AD patients for age and schooling. Before testing all
      participants were applied the Mini-Mental State Examination. Results showed
      significant differences in total scores of the tests; NEUROPSI (P<0.001) and Mini
      Mental State Examination (P<0.001), and the control group scored highest in both
      of the tests followed by groups AD1 and AD2. Differences were also found between
      the initial phase and the moderate phase. Results indicate that NEUROPSI is an
      efficient instrument for detecting AD patients in the initial stage of the
      disease.

PMID- 18317251
TI  - The Public's ability to recognize Alzheimer disease and their beliefs about its
      causes.
AB  - The authors report how the population identifies symptoms of Alzheimer disease
      (AD) and the causes attributed to this disorder in the city of Sao Paulo, Brazil.
      A total of 500 household residents aged 18 years and above were examined in a
      cross-sectional design, in Sao Paulo. Instruments were a case vignette depicting
      AD and a structured questionnaire. The symptoms of AD were identified by 46.4% as
      memory loss. The term AD was used in only 4% of the responses, although 39.4% of
      the respondents believed it was a mental illness. The main causes attributed were
      of psychosocial in nature: "drug use" and "isolation." Factors most influencing
      responses about causes were marital status, level of education, and economic
      status. In summary, medical-scientific concepts are not usually used in Sao
      Paulo. Causal attributions show that the laypersons' beliefs have important
      differences from the results of scientific evidence.

PMID- 18317252
TI  - The relationship between different pain assessments in dementia.
AB  - Persons with dementia have difficulty communicating, which has led to the
      underdetection and undertreatment of pain in this population. In this paper, we
      compare pain assessments using 3 different measurement types: self-report,
      informant rating, and observational assessments. Participants were 153 nursing
      home residents from 4 nursing homes. Four different self-report assessments were
      compared with 3 observational scales and 2 informant-based assessments, which
      included 3 summary rating scales. Only 60% of participants were able to complete
      at least 1 of the self-report assessments. The strongest correlations between
      assessments were found among instruments of the same type, that is, among the
      different self-report measures, among the different observational measures,
      between the 2 informant rating questionnaires, and among the 3 informant rating
      summary questions. Our results show that the different formats of pain
      assessments resulted in somewhat overlapping results, yet the differences were
      much larger than those obtained from different assessments within the same format
      type. The results reraise the questions of what pain is in this population, and
      whether the new assessments aimed to uncover such pain have targeted the correct
      construct. Results suggest that a multimethod type assessment may be needed to
      effectively manage pain.

PMID- 18317253
TI  - Health behavior changes after genetic risk assessment for Alzheimer disease: The
      REVEAL Study.
AB  - Risk information for Alzheimer disease (AD) may be communicated through
      susceptibility gene disclosure, even though this is not currently in clinical
      use. The REVEAL Study is the first randomized clinical trial of risk assessment
      for AD with apolipoprotein E (APOE) genotype and numerical risk estimate
      disclosure. We examined whether APOE genotype and numerical risk disclosure to
      asymptomatic individuals at high risk for AD alters health behaviors. One hundred
      sixty-two participants were randomized to either intervention (APOE disclosure)
      or control (no genotype disclosure) groups. Subjects in both groups received
      numerical lifetime risk estimates of future AD development based on sex and
      family history of AD. The intervention group received their APOE genotype.
      Subjects were informed that no proven preventive measures for AD existed and
      given an information sheet on preventative therapies under investigation.
      Participants who learned they were epsilon 4 positive were significantly more
      likely than epsilon 4 negative participants to report AD-specific health behavior
      change 1 year after disclosure (adjusted odds ratio: 2.73; 95% confidence
      interval: 1.14, 6.54; P=0.02). Post hoc analyses revealed similar significant
      associations between numerical lifetime risk estimates and self-report of AD
      specific health behavior change. Despite lack of preventive measures for AD,
      knowledge of APOE genotype, numerical lifetime risk, or both, influences health
      behavior.

PMID- 18317256
TI  - Medical software available for the blackberry.

PMID- 18317257
TI  - Nurses' perceptions of the impact of electronic health records on work and
      patient outcomes.
AB  - This study addresses community hospital nurses' use of electronic health records
      and views of the impact of such records on job performance and patient outcomes.
      Questionnaire, interview, and observation data from 46 nurses in medical-surgical
      and intensive care units at two community hospitals were analyzed. Nurses
      preferred electronic health records to paper charts and were comfortable with
      technology. They reported use of electronic health records enhanced nursing work
      through increased information access, improved organization and efficiency, and
      helpful alert screens. They thought use of the records hindered nursing work
      through impaired critical thinking, decreased interdisciplinary communication,
      and a high demand on work time (73% reported spending at least half their shift
      using the records). They thought use of electronic health records enabled them to
      provide safer care but decreased the quality of care. Administrative implications
      include involving bedside nurses in system choice, streamlining processes,
      developing guidelines for consistent documentation quality and location,
      increasing system speed, choosing hardware that encourages bedside use, and
      improving system information technology support.

PMID- 18317258
TI  - WebQuests: creating engaging, student-centered, constructivist learning
      activities.
AB  - Students entering health professions educational programs today have grown up and
      grown older in an unparalleled age of computers and connectivity. Yet most of
      these students face challenges in applying their information technology and
      information literacy abilities because most of them have never received formal
      training, have only a limited understanding of the tools they use, and underuse
      those tools. WebQuests are a unique method for enhancing students' information
      technology and information literacy competencies. As inquiry-oriented, engaging,
      and student-centered activities, WebQuests promote high-level thinking and
      problem-solving skills. Although WebQuests are used extensively in primary and
      secondary educational institutions, they have received limited attention in
      higher education settings. The authors describe the history of WebQuests and,
      using examples from a series of WebQuests used in an undergraduate informatics
      for healthcare course, offer specific guidelines for developing relevant
      WebQuests for nursing education.

PMID- 18317260
TI  - Use of personal digital assistants to support clinical reasoning in undergraduate
      baccalaureate nursing students.
AB  - The utility of personal digital assistant resources in healthcare practice and
      education presents new challenges for faculty due to changing device capabilities
      and software availability. Although there is a plethora of personal digital
      assistant resources available for use by healthcare providers, little is known
      about the effect on clinical reasoning in nursing students. The complexity of the
      healthcare arena precludes reliance on memory as a sole resource for problem
      solving because it can be unreliable. A personal digital assistant provides
      instant access to information on medical treatment options so reliance on memory
      alone is avoided. The aims of this study are to assess clinical reasoning when
      personal digital assistants are used as an information resource for nursing
      students. These findings have implications for the future nursing work force,
      including accurate differential diagnosis and diagnostic reasoning, reduction of
      medication errors, reduction of healthcare costs, and development of effective
      treatment protocols.

PMID- 18317261
TI  - Designing and delivering effective online nursing courses with the evolve
      electronic classroom.
AB  - This case study describes how the Evolve electronic course management system was
      used to deliver an online Trends and Issues in Nursing course for 53 nurses-in
      training at Our Lady of Lourdes School of Nursing. Evolve provided an open-ended,
      electronic course shell that supported the instructor's efforts to create an
      online learning environment using the seven principles of effective teaching. The
      course was evaluated with items from the Student Evaluation of Online Teaching
      Effectiveness and questions written to assess unique features of the Trends and
      Issues course. Results indicated that most learners perceived that the course was
      generally a positive learning experience and that constructivist-based principles
      were used to design and deliver instruction that effectively promoted student
      learning.

PMID- 18317262
TI  - Intentions of hospital nurses to work with computers: based on the theory of
      planned behavior.
AB  - The purpose of this study was to determine registered nurses' attitudes related
      to intent to use computers in the hospital setting as a predictor of their future
      behavior. The study was further aimed at identifying the relationship between
      these attitudes and selected sociological, professional, and personal factors and
      to describe a research model integrating these various factors. The study was
      based on the theory of planned behavior. A random sample of 411 registered nurses
      was selected from a single large medical center in Israel. The study tool was a
      Likert-style questionnaire. Nine different indices were used: (1) behavioral
      intention toward computer use; (2) general attitudes toward computer use; (3)
      nursing attitudes toward computer use; (4) threat involved in computer use; (5)
      challenge involved in computer use; (6) organizational climate; (7) departmental
      climate; (8) attraction to technological innovations/innovativeness; (9) self
      efficacy, ability to control behavior. Strong significant positive correlations
      were found between the nurses' attitudes (general attitudes and nursing
      attitudes), self-efficacy, innovativeness, and intentions to use computers.
      Higher correlations were found between departmental climate and attitudes than
      between organizational climate and attitudes. The threat and challenge that are
      involved in computer use were shown as important mediating variables to the
      understanding of the process of predicting attitudes and intentions toward using
      computers.

PMID- 18317263
TI  - Highlights of the AMIA 2007 fall symposium.

PMID- 18317264
TI  - Delaware Valley Nursing Computer Network (DVNCN) Conference: nursing informatics
      making evidence based documentation a reality.

PMID- 18317266
TI  - New insights into the pathoanatomy of spinocerebellar ataxia type 3 (Machado
      Joseph disease).
AB  - PURPOSE OF REVIEW: This review summarizes recent neuropathological findings in
      spinocerebellar ataxia type 3 and discusses their relevance for clinical
      neurology. RECENT FINDINGS: The extent of the spinocerebellar ataxia type 3
      related central nervous neurodegenerative changes has been recently
      systematically investigated in a series of pathoanatomical studies. These studies
      showed that the extent of the central nervous degenerative changes of
      spinocerebellar ataxia type 3 has been underestimated so far. The newly described
      pattern of central nervous neurodegeneration includes the visual, auditory,
      vestibular, somatosensory, ingestion-related, dopaminergic and cholinergic
      systems. These pathological findings were correlated with clinical findings and
      explain a variety of the spinocerebellar ataxia type 3 symptoms observed in
      clinical practice. SUMMARY: Systematic pathoanatomical analysis of
      spinocerebellar ataxia type 3 brains helps to understand the structural basis of
      this neurodegenerative disease and offers explanations for a variety of disease
      symptoms. This better understanding of the neuropathology of the condition has
      implications for the treatment of spinocerebellar ataxia type 3 patients and
      represents a basis for further biochemical and molecular biological studies aimed
      at deciphering the pathomechanisms of this progressive ataxic disorder.

PMID- 18317267
TI  - Medical genetics diagnostic evaluation of the child with global developmental
      delay or intellectual disability.
AB  - PURPOSE OF REVIEW: The review addresses the recent discovery of large-scale copy
      number variations in the human genome and advances in microarray technology which
      together have changed the clinical genetic diagnostic approach for children with
      global developmental delay. RECENT FINDINGS: Several publications in the last
      three years evaluate the diagnostic rate of array comparative genomic
      hybridization (aCGH) in the setting of global developmental delay; to date, the
      rate of etiologic diagnosis ranges from 4.8% to 20%, a potential doubling of the
      rate of diagnosis prior to the application of this technique. SUMMARY: Large
      scale copy number variations in the human genome leading to gene dosage
      imbalances comprise approximately 12% of the entire genome and some 10% of all
      known genes. Molecular testing for chromosome imbalances has changed with the
      application of array comparative genomic hybridization. Recent publications
      suggest a doubling of the rate of diagnosis of patients with genome copy number
      abnormalities as the cause of developmental delay. The use of array comparative
      genomic hybridization is replacing the use of fluorescent in-situ hybridization
      techniques for the child with idiopathic global developmental delay or
      intellectual disability.

PMID- 18317268
TI  - Neurodevelopmental outcomes of preterm infants.
AB  - PURPOSE OF REVIEW: Preterm birth is emerging as a major public health problem in
      the USA. Improvements in preterm birth and survival rates translate to increasing
      numbers of preterm survivors, and many develop motor, cognitive and sensory
      impairments. RECENT FINDINGS: The review discusses the recently reported
      prevalence of neurodevelopmental disabilities in preterm survivors, in addition
      to studies of factors associated with neurodevelopmental outcome. SUMMARY: A 2007
      report from the Institute of Medicine emphasizes preterm birth as an increasingly
      common complex condition with multiple risk factors resulting from multiple gene
      environmental interactions, leading to birth before 37 weeks gestation, neonatal
      complications and a disproportionately high contribution to neurodevelopmental
      disability rates. The increased risk of cerebral palsy with decreasing
      gestational age categories is well documented, but recent studies highlight the
      range and severity of cognitive, sensory, language, visual-perceptual, attention
      and learning deficits in very preterm children. Combined with increasingly
      sophisticated neuroimaging studies to identify perinatal risk factors,
      neurodevelopmental follow-up of neonatal intensive care unit trials offers the
      potential to really improve our understanding of how the preterm brain develops,
      is injured and recovers from injuries. Knowledge of what influences
      neurodevelopmental outcomes is key to developing better treatment strategies.

PMID- 18317269
TI  - Is cerebral palsy preventable?
AB  - PURPOSE OF REVIEW: To use evidence of good medical quality to update information
      on strategies for prevention of cerebral palsy, and on the success of these
      preventive efforts to date. RECENT FINDINGS: Causes of cerebral palsy, and
      therefore promising approaches to prevention, differ by gestational age group and
      by clinical subtype. Neuroimaging and neuropathology indicate the importance of
      white matter disorders and of ischemic stroke in cerebral palsy; birth asphyxia,
      congenital malformations, placental pathology, and genetic variants also
      contribute to cerebral palsy risk. Multiplicity of risk factors markedly
      increases risk. Recent studies indicate that mild hypothermia lessens cerebral
      palsy risk in term infants with moderate neonatal encephalopathy, and the
      possibility that administration of magnesium sulphate to women in preterm labor
      may aid in primary prevention of cerebral palsy in very preterm infants. SUMMARY:
      Past efforts to prevent cerebral palsy have not had the benefits sought, but
      recent results provide new hope and new challenges.

PMID- 18317270
TI  - Health and well being of adults with cerebral palsy.
AB  - PURPOSE OF REVIEW: This article reviews what is known about the health and well
      being of adults with cerebral palsy. It also addresses the factors known to
      affect the areas identified in the World Health Organization International
      Classification of Functioning model as being critical for optimal health and well
      being. RECENT FINDINGS: As adolescents with cerebral palsy progress to adulthood,
      they decrease their utilization of health and related services, in part because
      the transition to adult services is less than optimal. Adults with cerebral palsy
      have a high prevalence of comorbid and secondary conditions like pain. They have
      been shown to have regression in several areas of functioning including mobility.
      Adults with cerebral palsy also have less participation in areas such as social
      interactions, employment, marriage, and independent living than adults without
      cerebral palsy. Factors such as cognitive abilities, the severity of the cerebral
      palsy and age all affect participation. Very few studies have been done in adults
      to identify interventions that will help them achieve better health and well
      being. SUMMARY: The International Classification of Functioning can help identify
      areas in which research is needed to develop interventions that will optimize the
      health and well being of adults who have cerebral palsy.

PMID- 18317271
TI  - What is new in autism?
AB  - PURPOSE OF REVIEW: Autism is now recognized in one out of 150 children. This
      review highlights the topics within the growing autism literature that are
      shaping current thinking on autism and advancing research and clinical
      understanding of autism spectrum disorders. RECENT FINDINGS: The role of single
      stranded microdeletions and epigenetic influences on brain development has
      dramatically altered our understanding of the etiology of the autisms. Recent
      research has focused on the role of synapse structure and function as central to
      the development of autism and suggests possible targets of interventions. Brain
      underconnectivity has been a focus in recent imaging studies and has become a
      central theme in conceptualizing autism. Despite increased awareness of autism
      there is no 'epidemic' and no one cause for autism. Data from the sibling studies
      are identifying early markers of autism and defining the broader autism
      phenotype. SUMMARY: Larger datasets in genetics, a focus on the early signs of
      autism, and increased recognition of the importance of defining subgroups of
      children with autism are leading to a greater understanding of the etiologies of
      autism. A growing interest in defining the molecular biology of social cognition,
      which is at the core of autism, will lead to expansion of our presently limited
      choices of mechanistically based interventions.

PMID- 18317272
TI  - Progress in epilepsy: reducing the treatment gap and the promise of biomarkers.
AB  - PURPOSE OF REVIEW: Since the antiquities, the history of epilepsy has been
      characterized by ignorance and human suffering. People with epilepsy have
      benefited substantially from results of modern basic and clinical research;
      however, serious challenges remain. Two programs begun in the past decade offer
      the promise of even greater progress in the future. RECENT FINDINGS: The
      International League against Epilepsy, the International Bureau for Epilepsy and
      the WHO launched the Global Campaign against Epilepsy in 1997, which is using
      socioepidemiologic approaches to reduce the treatment gap and improve quality of
      life for people with epilepsy in the developing world. The US National Institute
      of Neurological Disorders and Stroke, and the American Epilepsy Society began a
      national neurobiological effort to move from targeting control of symptoms to
      strategies of prevention and cure, and in 2001 established benchmarks for future
      epilepsy research. The first of these benchmarks is to develop reliable
      biomarkers of epileptogenesis and epileptogenicity that could revolutionize our
      approach to diagnosis, treatment, prevention, and cure. SUMMARY: Epilepsy
      continues to be a major health burden worldwide. The Global Campaign against
      Epilepsy is leading the way towards universal acceptability of epilepsy and
      access to medical care. Among the many current neurobiological research
      objectives, development of reliable epilepsy biomarkers would be a major step
      toward realizing a world where no one is compromised by epilepsy.

PMID- 18317273
TI  - The multifaceted role of inhibition in epilepsy: seizure-genesis through
      excessive GABAergic inhibition in autosomal dominant nocturnal frontal lobe
      epilepsy.
AB  - PURPOSE OF REVIEW: While epilepsy describes a heterogeneous array of syndromes,
      the conventional view is that there is a common underlying failure in the ability
      of GABAergic inhibition to overcome excessive synaptic excitation. This review
      explores the possibility that enhanced GABAergic inhibition in the neocortex
      could also be proepileptogenic. RECENT FINDINGS: Recently, two mouse strains
      carrying mutant alleles of the alpha4 subunit of the nicotinic acetylcholine
      receptor that are associated with autosomal dominant nocturnal frontal lobe
      epilepsy have been found to show spontaneous seizures. Recordings from
      neocortical pyramidal neurons in vitro show that the autosomal dominant nocturnal
      frontal lobe epilepsy mutations are associated with large selective increases in
      nicotine-evoked GABAergic inhibition, which may be key factor in epileptogenesis,
      as the seizures in vivo are blocked by subconvulsive doses of the GABAA receptor
      antagonist, picrotoxin. SUMMARY: The precise links between the observed gain of
      neocortical inhibition and development of seizures in autosomal dominant
      nocturnal frontal lobe epilepsy mice remain unknown. Recent insights into the
      functional properties of cortical GABAergic circuits, however, suggest several
      possible pathways to be explored, whose elucidation could enable selective
      therapeutic interventions.

PMID- 18317274
TI  - Epileptic syndromes in infancy and childhood.
AB  - PURPOSE OF REVIEW: The aim of this article is to review new epilepsy syndromes,
      acquire a new understanding of older ones and emphasize the impact of this
      concept on basic research regarding aetiology and treatment. RECENT FINDINGS: In
      addition to those included in the classification of the International League
      Against Epilepsy, new epilepsy syndromes comprise febrile seizures plus, benign
      familial neonatal-infantile seizures (BFNIS), benign infantile focal epilepsy
      with midline spikes and waves during sleep (BFIS), malignant migrating partial
      seizures in infancy, devastating epilepsy in school age children and late onset
      cryptogenic spasms. Genetics played a central role in identifying some new
      entities (BFNIS, BFIS with choreoathetosis), to delineate older syndromes (Dravet
      syndrome and myoclonic astatic epilepsy) and determine their mechanisms
      (infantile spasms, pyridoxine dependent seizures, neonatal encephalopathy with
      suppression bursts). SUMMARY: A significant number of children, mainly infants,
      do not fit in any of the described epilepsy syndromes. Still many patients with
      infantile epilepsy require the identification of cause or recognition of an
      epilepsy syndrome.

PMID- 18317275
TI  - Strategy for utilization of new antiepileptic drugs.
AB  - PURPOSE OF REVIEW: The paper reviews strategies to incorporate new antiepileptic
      drugs into the treatment arsenal for patients with epilepsy. RECENT FINDINGS: Ten
      new antiepileptic drugs have been developed in the last two decades, making
      selection of optimal therapy complex; they have not been shown to have better
      efficacy but generally seem to be better tolerated. Newer antiepileptic drugs
      offer new opportunities to patients who have not had a favorable response to the
      old ones. Many new antiepileptic drugs exhibit a broad spectrum of activity while
      only one of the older ones (valproate) has a broad-spectrum profile. There are
      therefore more choices when trying to match treatment with epileptic seizures and
      syndromes. The side-effect profiles of the newer antiepileptic drugs differ from
      the older ones with fewer systemic reactions and better pharmacokinetics for the
      most part. SUMMARY: Comparative studies are needed to elucidate the specific
      weaknesses and strengths of each of the new antiepileptic drugs compared with the
      older ones. Most clinical trials do not help the physician in deciding drug,
      dose, or titration schedules. Thus the physician needs to understand efficacy
      spectrum and side-effect profiles of each new antiepileptic drug in order to be
      able to treat each patient optimally.

PMID- 18317276
TI  - The natural history of mesial temporal lobe epilepsy.
AB  - PURPOSE OF REVIEW: Mesial temporal lobe epilepsy is the most common indication
      for epilepsy surgery, yet little is known about its 'natural' history from
      initial onset. The review considers the available evidence and gaps in our
      current knowledge of the subject. RECENT FINDINGS: Although usually surgically
      treated in adulthood, the majority of people with refractory mesial temporal lobe
      epilepsy have their initial onset in childhood and adolescence. The course of the
      disorder is complex and may appear relatively benign at first with intractable
      seizures emerging only later. Early diagnosis of mesial temporal lobe epilepsy is
      made difficult due to the near absence of its MRI correlate, i.e. hippocampal
      atrophy, a lesion that seems to develop over time and is rarely present at
      initial onset. Early diagnosis is further complicated by the fact that there are
      likely many different entities that are localized to the temporal regions and are
      not clearly differentiated from each other initially. SUMMARY: Advances in
      understanding mesial temporal lobe epilepsy will require concerted efforts to
      characterize epilepsy with precision from onset and document its course over
      prolonged periods of time. Better recognition of specific subtypes currently
      lumped together as temporal lobe epilepsy is also needed.

PMID- 18317277
TI  - Early surgical treatment for epilepsy.
AB  - PURPOSE OF REVIEW: To review recent evidence that can assist clinicians facing
      the challenging question of when to offer brain surgery for epilepsy. RECENT
      FINDINGS: The most robust recent evidence pertains to temporal lobe epilepsy. We
      focus on this syndrome to assess the main issues pertaining to early surgery,
      which include natural history and effectiveness of medication, risks associated
      with continued seizures, effectiveness and risks of surgery, and cognitive
      outcomes in relation to timing of surgery. SUMMARY: The evidence for performing
      surgery earlier is persuasive but incomplete. Recent evidence indicates that
      intractability, and therefore consideration for surgery, does not develop at a
      uniform time in surgical candidates, and that late remissions with medical
      treatment are not rare. Factors that may suggest sustained intractability include
      a larger number of medications tried, longer duration of seizures, history of
      status epilepticus, mental retardation, and nonidiopathic epilepsy. Adequate
      prospective studies, however, need to address this important question
      systematically. The evidence regarding morbidity, quality of life, mortality,
      social and cognitive function suggests that earlier surgery may be beneficial,
      but prospective controlled studies with standardized interventions and outcomes
      will be required to derive firm conclusions.

PMID- 18317278
TI  - Complementary and alternative medical therapies.
AB  - PURPOSE OF REVIEW: Complementary and alternative medical therapies include herbs,
      acupuncture, and mind-body therapies. This review highlights the findings of
      recently published studies of complementary and alternative medical therapies and
      epilepsy, and provides an update of the US Food and Drug Administration's role in
      regulating herbal products. RECENT FINDINGS: Complementary and alternative
      medical therapies are often tried by patients with epilepsy, frequently without
      physician knowledge. Many modalities have been evaluated in patients with
      epilepsy, though methodological issues preclude any firm conclusions of efficacy
      or safety. Some herbal medicines have been shown experimentally to have
      mechanisms of action relevant to epilepsy and promising actions in animal models.
      SUMMARY: There is currently a paucity of credible evidence to support the use of
      complementary and alternative medical therapies in patients with epilepsy. Herbal
      medicines traditionally used for epilepsy and compounds isolated from them, as
      well as other herbal medicines and their constituent compounds that have been
      shown experimentally to have mechanisms of action relevant to epilepsy, should
      undergo further preclinical evaluation with a view towards clinical development
      under the new US Food and Drug Administration guidelines. Additional studies of
      other, nonherbal complementary and alternative medical therapies are also
      warranted based on anecdotal observations or pilot studies that suggest a
      favorable risk-benefit ratio.

PMID- 18317279
TI  - Depression in epilepsy: a complex relation with unexpected consequences.
AB  - PURPOSE OF REVIEW: The recent significant increase in research on depressive
      disorders in epilepsy has led to a greater recognition of its negative impact on
      multiple aspects of these patients' lives. Thus, a review of this topic could not
      be timelier. RECENT FINDINGS: A population-based study suggests that a lifetime
      history of depressive disorders is relatively frequent in epilepsy patients.
      Contrary to long-held beliefs, the relation between these two disorders is
      bidirectional and a history of depression can often be identified before the
      first seizure has ever happened. Such a relation is the expression of common
      pathogenic mechanisms operant in both conditions, among which decreased binding
      of serotonin-1A receptors appears to be pivotal. Furthermore, a lifetime history
      of depression preceding the onset of epilepsy appears to be predictive of worse
      seizure control with pharmacotherapy and epilepsy surgery. SUMMARY: These data
      are likely to change the way the relation between depression and epilepsy is
      conceptualized, to enhance the early recognition and treatment of this disorder
      and to generate further research on the impact of depressive disorders on seizure
      response to pharmacologic and surgical treatments.

PMID- 18317280
TI  - Psychogenic nonepileptic seizures.
AB  - PURPOSE OF REVIEW: This review summarizes the recent studies assessing patients
      with psychogenic nonepileptic seizures and developments in treatment. RECENT
      FINDINGS: The misdiagnosis of nonepileptic seizure is costly to patients, the
      healthcare system, and to society. Patients with nonepileptic seizures are
      prescribed antiepileptic drugs that do not treat nonepileptic seizures, have
      multiple laboratory tests performed, and may not receive the necessary mental
      healthcare that could benefit them.The first step in nonepileptic seizure
      treatment is proper diagnosis. Video electroencephalography remains the gold
      standard for nonepileptic seizure diagnosis. Certain seizure types, such as
      frontal lobe seizures, may mimic nonepileptic seizure semiology. Bedside
      observations may augment video electroencephalography to establish nonepileptic
      seizure diagnosis. The methodology in nonepileptic seizure treatment trials is
      examined, describing the challenges in conducting clinical trials with patients
      with overlapping neurologic and psychiatric disorders. Finally, realizing that
      nonepileptic seizures are in a spectrum of somatoform disorders, diagnostic
      literature is reviewed in other conversion disorders. SUMMARY: Nonepileptic
      seizure patients remain one of the most challenging populations to diagnose and
      treat in medical practice. Clinical findings and laboratory advances exist that
      more clearly establish the diagnosis of nonepileptic seizures. With the
      appropriate diagnosis, neurologists and mental health providers are better
      equipped to treat the underlying causes of nonepileptic seizures.

PMID- 18317281
TI  - Bibliography. Current world literature. Developmental disorders.

PMID- 18317282
TI  - Flow and the balanced life.

PMID- 18317283
TI  - Development, testing, and national evaluation of a pediatric Patient-Family
      Centered Care benchmarking survey.
AB  - This study provides evidence for reliability (the Cronbach alpha of .76-.94) and
      construct validity of the Patient-Family-Centered Care Survey developed by the
      researchers in collaboration with FKP Architects, used to measure and benchmark
      practice within pediatric institutions. The survey evaluates progress of
      integrating patient-family-centered care over time and can be triangulated with
      measurements of desired patient and institutional outcomes.

PMID- 18317285
TI  - Innovation in nursing education: preparing for the future of nursing practice.

PMID- 18317286
TI  - A holistic approach to severe depression: my story.
AB  - Given the prevalence of major depressive disorder (MDD) and its significant
      economic and personal costs to society, families, and those with MDD, and given
      the frequent failure of contemporary therapeutics to treat MDD, it is imperative
      that nurses explore holistic approaches to managing MDD. My story provides a case
      study for how several approaches can be blended to holistically manage MDD. The
      approach that is effective for me requires faithfully attending to diet,
      exercise, sunlight, sleep, and spirituality, as well as continuing to receive
      psychological and social support.

PMID- 18317287
TI  - Meaning holism in caring practice.
AB  - Drawing on Ludwig Wittgenstein's influential theory of concept possession, the
      article argues that assumptions about meaning in patients' linguistic communities
      normally play an important role in nurse-patient communication. Case studies are
      used to clarify the significance of the sociocultural dimension of understanding
      in caring practice.

PMID- 18317288
TI  - The effect of essential oils on work-related stress in intensive care unit
      nurses.
AB  - This small pilot study evaluated the effect of a topical application of the
      essential oils Lavandula angustifolia and Salvia sclaria on work-related stress
      of nurses in an ICU setting. Results demonstrated decreased perception of stress
      level in the intervention group during three 12-hour worked shifts.

PMID- 18317289
TI  - Effect of Healing Touch on stress perception and biological correlates.
AB  - The objective of this pilot study was to investigate the effect of Healing Touch
      on state/trait anxiety and physiological measures of heart rate, blood pressure,
      muscle tension, skin conductance, and skin temperature in healthy adults. The
      study used a single group, repeated measures design with a nonprobability
      convenience sample of 30 subjects. Physiological data were collected for 10
      minutes before intervention, during 30 minutes of Healing Touch treatment, and
      for 10 minutes posttreatment. During the course of the treatment, changes were
      observed for all psychological and physiological measures, with the exception of
      muscle tension that remained constant. Results suggest that Healing Touch
      treatment is associated with both physiological and psychological relaxation.
      Further study is warranted to explore the efficacy of Healing Touch as an
      intervention for stress in healthy adults.

PMID- 18317290
TI  - Nursing students' reflections on racism.
AB  - Racism is the systematic oppression of people of color at personal/interpersonal,
      institutional, and/or cultural levels. Discussions about racism often become
      emotional and personal. A discussion related to the accurate labeling of students
      on the basis of their heritage in an undergraduate professional issues class
      became emotionally charged. To prevent any further escalation of emotions, the
      author brought closure by asking students to read and write a reflective response
      to the Black Prayer. This article is a summary of urban nursing students'
      reflections and how giving voice to such reflections is a way of opening the door
      to frank discussions of racism and its effects.

PMID- 18317291
TI  - Forever young ... Living as young, as old as possible.

PMID- 18317292
TI  - Revised fundamental recommendations on radiological protection.

PMID- 18317293
TI  - Factors influencing radioguided surgery of neuroendocrine tumours using 99mTc
      ethylenediamine N,N'-diacetic acid/6-Hydrazinopyridine-3-carboxylic acid-D-Phe1
      Tyr3-octreotide.
AB  - OBJECTIVE: To determine factors influencing radioguided surgery of neuroendocrine
      tumours using Tc-ethylenediamine N,N'-diacetic acid/6-Hydrazinopyridine-3
      carboxylic acid-D-Phe-Tyr-octreotide and gamma-probe. METHODS: Patients with 17
      neuroendocrine tumours were operated on. Three to 6 h before surgery, 550-650 MBq
      of Tc-labelled octreotide were injected into the patients. Scintigraphy was
      performed immediately before surgery to confirm uptake of the radiopharmaceutical
      by the tumour. The uptake was graded on a scale from 0 to 4. Local measurements
      of radioactivity were performed during surgery using a gamma-probe and small lead
      shields. RESULTS: Intraoperatively 12 tumours in 11 patients were successfully
      localized using a gamma-probe: three tumours with uptake grade 4, seven with
      grade 3 and two with grade 2. Seven tumours were localized in the region of the
      pancreas, two next to the aortic bifurcation, one in the mesentery and two in the
      ileocecal region. Tumours were not found in five patients. They were all positive
      on scintigraphy with tracer uptake grade 4 in one patient, grade 3 in one, and
      grade 2 in three patients. Localization was confirmed by endoscopic ultrasound,
      computed tomography and/or MRI. All five tumours were located in the pancreatic
      area. In four of these patients, tumours were seen in the same localization as
      preoperatively on follow-up scintigraphy 6-12 months later. CONCLUSION: Factors
      influencing the success of surgery were high octreotide uptake (grades 3 and 4)
      and localization of the tumour away from kidneys and spleen. Positive
      localization on endoscopic ultrasound, computed tomography or MRI, size of
      tumour, pathohistology and reoperations did not influence surgical success.

PMID- 18317294
TI  - The impact of superficial injections of radiocolloids and dynamic
      lymphoscintigraphy on sentinel node identification in oral cavity cancer: a same
      day protocol.
AB  - AIM: To evaluate the role of dynamic lymphoscintigraphy with a same-day protocol
      for sentinel node biopsy in oral cavity cancer. METHODS: Twenty-two consecutive
      patients affected by cT1-2N0 squamous cell carcinoma of the oral cavity were
      enrolled between September 2001 and November 2005. After a local anaesthetic (10%
      lidocaine spray), a dose of 30-50 MBq of Tc human serum albumin nanocolloid, in
      ml saline, was injected superficially (1-2 mm subendothelial injection) into four
      points around the lesion. Dynamic lymphoscintigraphy was acquired immediately
      (256x256 matrix, 5 min pre-set time, LEGP collimator) in lateral and anterior
      projections. The imaging was prolonged until the lymph nodes of at least two neck
      levels were visualized (time required min). About 3 h later (same-day protocol)
      the patients had a radioguided sentinel node biopsy. Elective neck dissection was
      performed in the first 13 patients; whereas the last nine patients had elective
      neck dissection only if the sentinel node was positive. Sentinel nodes were
      dissected into 1 mm thick block sections and studied by haematoxylin & eosin
      staining and immunohistochemistry (anticytokeratin antibody). RESULTS: The
      sentinel nodes were found on the 1st neck level in 13 cases, on the 2nd neck
      level in eight cases, and on the 3rd neck level in one case (100% sensitivity).
      The average number of sentinel nodes was 2.2 for each patient. The sentinel node
      was positive in eight patients (36%); with six of them having the sentinel node
      as the exclusive site of metastasis. No skip metastases were found in the 14
      patients with negative sentinel node (100% specificity). CONCLUSION: Our
      preliminary data indicate that superficial injections of radiocolloid and dynamic
      lymphoscintigraphy provide a high success rate in sentinel node identification in
      oral cavity cancers. Dynamic lymphoscintigraphy helps in distinguishing sentinel
      node from second-tier lymph nodes. The same-day protocol is advisable in order to
      correctly identify the first sentinel node, avoiding multiple and unnecessary
      node biopsies, without reducing sensitivity.

PMID- 18317295
TI  - A clinical comparison between traditional planar V/Q images and planar images
      generated from SPECT V/Q scintigraphy.
AB  - PURPOSE: To compare interpretation of traditional planar ventilation-perfusion
      lung scan images with planar images reformatted from single photon emission
      computed tomography (SPECT) data using two different techniques. METHODS: Planar
      and SPECT ventilation-perfusion (V/Q) data were acquired from 50 patients
      referred with suspected pulmonary embolism. In addition to traditional six-view
      planar images, six-view planar images were also generated from SPECT data using
      two methodologies: an angular summing technique (angular summed planar images)
      and a forward projection technique (reprojected planar images). Three experienced
      nuclear medicine clinicians reviewed the images in a blinded, randomized fashion.
      Results were analysed by comparing the two reprojected techniques with the
      traditional true planar scans, examining for differences in the defects seen
      (number, type and confidence), and the impact on final clinical interpretation.
      RESULTS: Compared with true planar scintigraphy, angular summed images
      demonstrated fewer mismatched defects (P<0.0001), while the reprojected planar
      images had more matched defects (P=0.013). In addition, there was a significant
      change in the clinical interpretation of the angular summed planar images
      resulting in clinicians perceiving a decreased likelihood of pulmonary embolism
      (P<0.016). No such difference in interpretation was observed for the reprojected
      planar images. CONCLUSIONS: Angular summed planar images result in a perceived
      decreased likelihood of pulmonary embolism compared with true planar images. In
      contrast, while reprojected planar images result in an increased number of
      matched defects compared to true planar scans, there was no change in the
      clinical interpretation. Caution should be exercised when interpreting SPECT
      derived angular summed planar images in isolation.

PMID- 18317296
TI  - Diagnosis of infected total knee arthroplasty with anti-granulocyte scintigraphy:
      the importance of a dual-time acquisition protocol.
AB  - OBJECTIVE: To evaluate clinical efficacy of a dual-time acquisition protocol
      consisting of early 4 h and delayed 20-24 h imaging with anti-granulocyte
      scintigraphy (LeukoScan) in the diagnosis of infection in painful total knee
      arthroplasty (TKA). MATERIALS AND METHODS: Seventy-eight consecutive patients
      with TKA (12 bilateral) were prospectively enrolled in the study from August 2004
      to July 2005. All the patients had clinical and biochemical suspicious of
      infection, except for the 12 patients with bilateral painless prosthesis who had
      no signs and symptoms of loosening and/or infection and were considered as
      controls. TKA prostheses had been implanted 4 months to 9.5 years before our
      studies. Forty-three patients were on antibiotic therapy at the moment of
      scintigraphic examination, and treatment was not discontinued. All patients
      underwent LeukoScan examination by performing both early 4 h and delayed 20-24 h
      imaging. In addition to planar imaging SPECT was performed in 18 cases. A
      decrease in radiotracer uptake from early to delayed LeukoScan imaging was
      interpreted as an unspecific finding (negative for infection), while an
      increasing uptake was interpreted as a positive finding for the presence of
      infection. Three-phase Tc-MDP bone scan was also routinely performed by standard
      technique. Sensitivity and specificity of early and delayed LeukoScan imaging
      were calculated. RESULTS: Sensitivity for early and delayed imaging were 92.7%,
      while specificity was 78.4% for early imaging and 100% for delayed imaging
      approach. SPECT imaging did not add any significant information as regard to
      specificity in our experience. Eight false positive early scans were correctly
      diagnosed as negative at delayed imaging. Three false negative results were
      recorded. Sensitivity and specificity were similar when patients were on or off
      antibiotic therapy. Imaging was negative in all 12 controls. CONCLUSIONS: Our
      results, based on a large group of patients, suggest that delayed LeukoScan
      imaging is important in identifying false positive results detect at early
      imaging. Thus, a dual-time, 4 h early and 20-24 h delayed LeukoScan imaging
      approach should be recommended to increase the diagnostic accuracy of the
      scintigraphy, with the exception of patients with a negative early LeukoScan
      examination, in whom the acquisition of delayed imaging appears unnecessary. In
      our experience, concomitant antibiotic therapy did not influence the diagnostic
      value of LeukoScan.

PMID- 18317297
TI  - Systemic and local release of inflammatory cytokines regulates hepatobiliary
      excretion of 99mTc-mebrofenin.
AB  - OBJECTIVES: Imaging agents capable of providing cell compartment-specific
      information will facilitate studies of pathophysiological mechanisms, natural
      history of diseases, and therapeutic development. To demonstrate the effects of
      liver injury on the disposal of the organic anion mebrofenin, we performed animal
      studies. METHODS: Acute liver injury was induced in Fischer 344 rats with 0.25-1
      ml/kg single doses of carbon tetrachloride followed by studies of animals over 4
      weeks. The liver injury was analyzed by blood tests and histological grading.
      Additional rats were treated with lipopolysaccharide, interleukin-6 or tumor
      necrosis factor-alpha to activate inflammatory events. Hepatic clearance of Tc
      mebrofenin was studied with dynamic imaging and fractional retention after 60 min
      of peak hepatic mebrofenin activity was determined. RESULTS: In healthy rats,
      only 24+/-2% of peak mebrofenin activity was retained in the liver after 60 min.
      By contrast, 24 h after carbon tetrachloride, virtually all mebrofenin activity
      was retained in the liver (P<0.001). Three weeks were required for mebrofenin
      excretion to become normal after carbon tetrachloride administration. In this
      situation, we found that Kupffer cell activity was increased. In addition, the
      abnormality in mebrofenin excretion was reproduced by lipopolysaccharide, which
      activates Kupffer cells. Moreover, mebrofenin excretion was highly sensitive to
      interleukin-6 and/or tumor necrosis factor-alpha, which help mediate the Kupffer
      cell response. CONCLUSION: Hepatobiliary excretion of mebrofenin was affected
      rapidly and over an extended period by inflammatory cytokines released after
      liver injury. The remarkable sensitivity of mebrofenin excretion to cytokines
      suggests that Tc-mebrofenin imaging will be helpful for assessing cytokine
      mediated liver inflammation.

PMID- 18317298
TI  - Pixel-by-pixel mean transit time without deconvolution.
AB  - BACKGROUND: Mean transit time (MTT) within a kidney is given by the integral of
      the renal activity on a well-corrected renogram between time zero and time t
      divided by the integral of the plasma activity between zero and t, providing that
      t is close to infinity. However, as the data acquisition of a renogram is finite,
      the MTT calculated using this approach might result in the underestimation of the
      true MTT. To evaluate the degree of this underestimation we conducted a
      simulation study. METHODS: One thousand renograms were created by convoluting
      various plasma curves obtained from patients with different renal clearance
      levels with simulated retentions curves having different shapes and mean transit
      times. RESULTS: For a 20 min renogram, the calculated MTT started to
      underestimate the MTT when the MTT was higher than 6 min. The longer the MTT, the
      greater was the underestimation. Up to a MTT value of 6 min, the error on the MTT
      estimation is negligible. CONCLUSION: As normal cortical transit is less than 2
      min, this approach is used for patients to calculate pixel-to-pixel cortical mean
      transit time and to create a MTT parametric image without deconvolution.

PMID- 18317299
TI  - Striatal dopamine transporter abnormalities in patients with essential tremor.
AB  - BACKGROUND AND METHODS: We used (123)I-Ioflupane SPECT to study 32 unrelated
      patients with essential tremor (16 with positive familial history), 47 sporadic
      tremor dominant patients with Parkinson's disease and 31 healthy control
      subjects. Discriminant analysis was used to categorize healthy subjects and
      patients with Parkinson's disease or essential tremor. RESULTS: Patients with
      essential tremor had higher uptake values (50% putamen and 21% caudate, P<0.001)
      compared to those with Parkinson's disease but lower than healthy subjects (15%
      putamen and 21% caudate, P<0.05). Discriminant analysis classified seven
      essential tremor patients in the healthy subjects cohort (22%) and two as
      Parkinson's disease (6%). CONCLUSIONS: Our results show that some essential
      tremor patients may present mild abnormalities of striatal dopamine transporters
      and a typical Parkinson's disease-like pattern of uptake loss. These findings
      suggest a link between the two disorders.

PMID- 18317300
TI  - Misdiagnoses of 11C-choline combined with 18F-FDG PET imaging in brain tumours.
AB  - BACKGROUND AND OBJECTIVE: The widely applied F-FDG is known for its disadvantage
      in brain tumour PET imaging because of its high background uptake. C-choline can
      achieve high contrast of brain tumour imaging and was expected to have higher
      sensitivity and specificity. We analysed the misdiagnoses in C-choline PET
      imaging in brain tumours with the aim of improving the accuracy of diagnosis with
      C-choline PET imaging. PATIENTS AND METHODS: We selected 10 patients proven to
      have been misdiagnosed on the basis of histopathological correlation and clinical
      follow-up among 94 patients (110 studies) who underwent C-choline PET/CT for
      diagnosed or suspected brain tumour between 23 March 2005 and 8 February 2007. C
      choline PET imaging were performed on a Biograph Sensation 16 PET/CT scanner
      (Siemens Medical Systems), F-FDG imaging was also performed as reference.
      RESULTS: Of all 10 misdiagnosed patients, five were false positive (one abscess,
      one tuberculosis, one benign gliocyte proliferation, one inflammatory granuloma
      and one demyelination), four were false negative (two metastases from lung
      cancer, one lymphoma, one grade II glioma) and one was misdiagnosed by wrong
      interpretation due to lack of experience. The rate of false positives was (5/110)
      4.55%; the rate of false negatives was (4/110) 3.64%; the accuracy of C-choline
      alone was (93/110) 84.5%; by comparison, the accuracy of F-FDG alone was (78/110)
      70.9%. CONCLUSIONS: C-choline imaging has a certain rate of false positivity and
      false negativity. With proper application, C-choline might have greater potential
      than F-FDG for brain tumour PET imaging.

PMID- 18317301
TI  - Correcting tumour SUV for enhanced bone marrow uptake: retrospective 18F-FDG
      PET/CT studies.
AB  - PURPOSE: The concentration of F-FDG in the bone marrow is usually low. One common
      cause of high uptake is due to bone marrow stimulating drugs administered in
      conjunction with chemotherapy or radiation therapy. It has been hypothesized that
      the sequestration of F-FDG to the bone marrow may reduce the standardized uptake
      value (SUV) of a tumour. We tested this hypothesis by quantifying total F-FDG
      uptake in the bone marrow of patients with visibly enhanced bone marrow uptake
      and computing its effect on tumour SUV. METHODS: Total F-FDG in bone marrow was
      measured in two groups of PET/CT studies: one (n=19) with visibly enhanced bone
      marrow, the other (n=5), a baseline group with 'normal' levels of uptake. To
      measure the F-FDG in bone marrow, the entire skeleton in the CT was segmented
      from surrounding tissue, and the resulting volume applied to the PET image. Using
      kinetic analysis we show that the predicted correction factor to tumour SUV is
      given by (1-q0/Q)/(1-q/Q), where Q is the injected dose, and q and q0 are
      enhanced and baseline bone marrow uptake (MBq). RESULTS: The enhanced bone marrow
      uptake averaged 8.9+/-3.2% of injected dose (15.2% max) vs. 4.2+/-0.4% (4.6% max)
      at baseline. This resulted in a predicted artificial decrease in tumour SUV of up
      to 11.5% (4.9+/-4.3%, on average). CONCLUSION: Enhanced bone marrow uptake is
      predicted to reduce tumour SUVs by as much as 11.5% in our patient group and is a
      potential confounding factor in using SUV for monitoring tumour response to
      therapy.

PMID- 18317302
TI  - Significance of incidental fluorodeoxyglucose uptake in the parotid glands and
      its impact on patient management.
AB  - BACKGROUND AND OBJECTIVES: Minimal-to-low grade fluorodeoxyglucose (FDG) uptake
      in the parotid glands is regarded as a normal variant in a whole-body survey with
      FDG-PET. Not frequently, however, a relatively intense or asymmetric FDG uptake
      is encountered in the parotid glands. The aim of this study was to determine the
      causes and characteristics of this 'FDG accumulation of uncertain significance'
      in the parotid glands in patients without any known or suspected pathologies at
      the time of whole-body FDG-PET. In addition, we also examined patients in whom
      there was no documented evidence of parotid pathology before FDG-PET scan and a
      suspicion of disease involvement was first raised in the reports in view of focal
      uptake in the FDG-PET images. MATERIALS AND METHODS: A total of 25 patients with
      49 PET examinations [46 PET and three PET/computed tomography (CT) scans] were
      identified from the retrospective examination of PET reports and were analyzed in
      this study. Only those cases with no earlier history of disease involvement of
      parotid gland or known parotid pathology before FDG-PET were selected for this
      analysis. These patients were selected from a population of patients with a known
      malignancy elsewhere who underwent conventional whole-body FDG-PET or PET/CT for
      staging, disease viability assessment, or treatment monitoring purposes and had
      demonstrated varying patterns of FDG uptake (unilateral, bilateral, symmetric, or
      asymmetric) in the parotid glands. FDG uptake in the parotid glands was reported
      to be of uncertain significance in the majority of these patients and further
      correlation was suggested in the PET reports. In five patients with asymmetric
      and focally enhanced FDG uptake, a suspicion of disease involvement was raised in
      the reports. The results of appropriate correlative investigations with MRI, low
      dose nonenhanced attenuation CT images (based on PET/CT scans), and
      histopathology (in cases in which focal lesions were revealed by the anatomic
      imaging modalities and biopsy was performed) carried out subsequent to the FDG
      PET scans were reviewed for a definitive conclusion with regard to the
      significance of the FDG uptake in the parotid glands in these patients. In the
      absence of any focal pathology, clinical and follow-up FDG-PET data were reviewed
      for a logical conclusion, which were available in a majority of these patients.
      Standardized uptake values (maximum) were calculated by generating a manual
      region of interest over FDG activity. The pattern and the intensity of the FDG
      uptake were correlated with the final diagnosis. RESULTS: In six of the 25
      patients with diffuse and symmetrical FDG uptake no clearcut pathology was
      demonstrated by clinical or radiological examinations. Five patients of this
      subgroup also demonstrated associated enhanced FDG activity in the submandibular
      salivary glands. Nineteen patients (76%) demonstrated asymmetric FDG uptake.
      Among these, focally enhanced uptake was observed in seven patients (28% of the
      total number of patients and 36.8% of the patients who demonstrated asymmetric
      FDG uptake in the parotids). Twelve patients (48% of total patients and 63.2% of
      the patients who demonstrated asymmetric FDG uptake) demonstrated asymmetric and
      diffuse FDG uptake pattern. No revelation of disease either by the MRI or follow
      up clinical and FDG-PET examinations was observed in patients with asymmetric
      diffuse uptake. Five of the seven patients, who had asymmetric focal uptake in
      one of the parotids, were found to have focal lesions in either correlative MRI
      or low-dose nonenhanced CT. The final diagnosis based upon histopathology
      revealed primary parotid tumors (e.g., Warthin's tumor and pleomorphic adenoma,
      which presented as FDG-avid parotid incidentaloma) or metastatic disease
      involvement. CONCLUSION: Both the pattern and intensity of FDG uptake have
      important implications for differential diagnosis in the salivary glands in whole
      body FDG-PET. A bilaterally symmetrical increased uptake is usually
      physiological. An asymmetrical uptake, especially when focal, would warrant
      further radiological and histopathological correlation to rule out disease
      involvement. At times, this can lead to the detection of an asymptomatic hitherto
      unknown etiology, which would have been otherwise interpreted as a metastatic
      disease in the background of an existing malignancy in these patients; this is
      noteworthy as it may have a bearing on the subsequent management of these
      patients.

PMID- 18317303
TI  - Repeatability and reproducibility of phase analysis of gated single-photon
      emission computed tomography myocardial perfusion imaging used to quantify
      cardiac dyssynchrony.
AB  - BACKGROUND: A novel method to quantify dyssynchrony has been developed using
      phase analysis of gated single-photon emission computed tomography perfusion
      imaging. We report on the effect of variability in image reconstruction on the
      phase analysis results (repeatability) and on the interobserver and intraobserver
      reproducibility of the technique. METHODS: Phase standard deviation (SD) and
      bandwidth are phase indices that quantify dyssynchrony. To evaluate
      repeatability, raw data sets were processed twice in 50 patients with left
      ventricular dysfunction and 50 normal controls. To determine the optimal
      processing method, two replicated phase analysis results were obtained using
      automated and manual base parameter placement. Reproducibility of the phase
      analysis was determined using the data from 20 patients. RESULTS: In normal
      controls, manual base parameter placement improves repeatability of the phase
      analysis as measured by the mean absolute difference between two reads for phase
      SD (12.0 degrees vs. 1.2 degrees , P<0.0001) and bandwidth (33.7 degrees vs. 3.6
      degrees , P<0.0001). Repeatability is better for normal controls than for
      patients with left ventricular dysfunction for phase SD (1.2 degrees vs. 6.0
      degrees , P<0.0001) and bandwidth (3.6 degrees vs. 26.5 degrees , P<0.0001).
      Reproducibility of the phase analysis is high as measured by the intraclass
      correlation coefficients for phase SD and bandwidth of 0.99 and 0.99 for the
      interobserver comparisons and 1.00 and 1.00 for the intraobserver comparisons.
      CONCLUSION: A novel method to quantify dyssynchrony has been developed using
      gated single-photon emission computed tomography perfusion imaging. Manual base
      parameter placement reduces the effect that variability in image reconstruction
      has on phase analysis. A high degree of reproducibility of phase analysis is
      observed.

PMID- 18317304
TI  - Apical thinning: real or artefact?
AB  - BACKGROUND AND OBJECTIVE: Apical thinning is a well-known phenomenon in
      myocardial perfusion SPECT, often attributed to reduced myocardial thickness at
      the apex of the left ventricle. Attenuation correction processing appears to
      exaggerate this effect. Although currently there is agreement that reduced apical
      counts are not a diagnostic indicator, opinions differ over the cause of this
      effect; we sought to clarify this using results from a phantom study. METHODS: A
      commercially available anthropomorphic torso phantom was expanded using
      attachments mimicking tissue and bone to create three phantoms of increasing
      size. These were imaged using a dual-headed gamma camera and low-dose CT-based
      attenuation correction. The data were processed using iterative reconstruction,
      with and without attenuation correction. RESULTS: The cardiac insert had a
      uniform wall thickness and yet defects characteristic of apical thinning appeared
      after attenuation correction, increasing in severity with phantom size. Before
      attenuation correction, a flare of activity was seen at the apex corresponding in
      position and size to the defect after attenuation correction. Further
      investigations showed the following: depth-dependent resolution was not
      responsible; the severity of the defect was more noticeably dependent on the
      addition of breast activity than the addition of attenuating material; the
      artefact was not unique to one particular algorithm; increasing the number of
      iterations reduced the severity of the artefact. CONCLUSION: Data acquisition and
      processing methods are thought to be responsible for the apparent apical defect.
      This phantom study therefore demonstrates that apical thinning is not simply an
      anatomical feature but can also be an artefact introduced by the use of
      attenuation correction.

PMID- 18317305
TI  - Synergistic impact of attenuation correction and gating in routine myocardial
      SPECT reporting: 2 year follow-up study.
AB  - AIM: To look at the combined impact of non-uniform attenuation correction (AC)
      and gated SPECT in the visual interpretation of myocardial SPECT imaging. This
      was compared to the individual benefit obtained by adding AC information and
      gated SPECT information to non-AC image information. MATERIALS: We
      retrospectively studied a group of 141 patients with a 22-26 month follow-up who
      underwent myocardial perfusion scintigraphy imaging. All the studies were
      corrected for attenuation with Gd line source transmission data and were ECG
      gated. In patients who had abnormal studies, follow-up coronary angiography
      information was also obtained in addition to medical follow-up information.
      METHODS: Two experienced nuclear medicine physicians interpreted the images
      independently and were blinded to the other person's report. Non-attenuation
      corrected data was first evaluated followed by attenuation corrected data and
      gated SPECT data. Four approaches to interpretation of images were undertaken:
      (1) non-AC images only, (2) non-AC+AC images, (3) non-AC+gated images, and (4)
      non-AC+AC+gated images. Study results were divided into four categories based on
      how confident the observers were of the diagnosis: (1) normal, (2) borderline
      normal, (3) borderline abnormal, and (4) abnormal. RESULTS: When results for
      sensitivity and specificity using the four different interpretation techniques
      were compared there was a statistically significant improvement in the
      specificity compared to non-AC image (48%) with the addition of AC (77%) and
      gating (82%) information (P<0.001). The best improvement in the specificity was
      noted when both AC and gated information (91%) was used along with non-AC
      information. The normalcy rates almost doubled following the addition of AC and
      gated data. There was also a decrease in the number of borderline results,
      showing an improvement in the reporter confidence in interpreting myocardial
      SPECT studies. Sensitivity, however, did not show a significant change between
      the four different approaches to interpretation of the study. CONCLUSION:
      Attenuation correction and gating when combined have a synergistic impact upon
      improving the specificity of myocardial SPECT reporting when compared to the use
      of individual techniques alone to improve the specificity.

PMID- 18317306
TI  - Influence of various geometric factors on the iodine-131 uptake measurement for
      solitary thyroid nodules.
AB  - AIM: The influence of various geometric factors on I uptake measurements for
      solitary thyroid nodule was systematically investigated to derive an approach,
      based on routinely performed ultrasound examinations, to correct for the effect
      of geometric variations. METHODS: The influence of size, shape, and position of a
      thyroid nodule, neck-to-detector distance and neck curvature on the uptake value
      was analyzed with a three-dimensional model. Uptake measurements using a tissue
      equivalent neck phantom were carried out to verify the calculated correction
      factors and also to check the influence of scatter. Sonograms of 92 patients with
      solitary nodules were analyzed to correct for geometric variations. RESULTS: The
      correction factors were independent of the size and shape of the nodule, and the
      activity distribution of the solitary nodules can be approximated by a point
      source. The correction factors were mainly determined by the nodular depth and by
      the accuracy of the neck-to-detector distance and were affected to a lesser
      extent by the lateral position of the nodule as well as the curvature of the
      neck. The effect of scatter can be neglected if the energy window largely
      excludes Compton scatter, as is the case in the I uptake measurement. The
      ultrasound-derived correction factors ranged from 0.85 to 1.25. CONCLUSION: The
      proposed approach is capable of correcting for the geometric variation for a
      solitary nodule and can be easily applied in routine clinics. The accuracy of
      absorbed dose in radioiodine therapy can be improved in particular for nodules
      located well beneath the neck surface.

PMID- 18317307
TI  - Exposure of medical personnel to radiation during radionuclide therapy practices.
AB  - OBJECTIVES: Radioisotopes that emit beta radiation are used for the treatment of
      hepatocellular carcinoma, of arthritic patients (radiosynovectomy) and treatment
      of bone metastases with, respectively, I-labelled lipiodol, colloidal citrate of
      Y or and Sm-labelled EDTMP. Radiation energy of these radioisotopes that emit
      beta or beta and gamma radiation (from 300 to 2000 keV) leads to an increase in
      radiation dose received by nuclear medicine staff. In this paper we focused on
      clinical and laboratory staff exposure during these types of metabolic radiation
      therapies. METHODS: Cylindrical LiF thermoluminescence dosimeters were used to
      measure radiation-related whole-body doses (WBDs) and finger doses of the
      clinical staff. RESULTS: Exposure of the two radiopharmacists and three nurses
      taking part in I-labelled lipiodol, Y-colloid and Sm-EDTMP therapies, for 12
      months in succession, were 146 microSv and 750 microSv, respectively, considering
      WBD, and 14.6 mSv and 6.5 mSv, respectively, considering finger doses.
      Extrapolated annual exposures (six radiosynovectomies per year) for the
      rheumatologists were estimated to be 21 microSv (WBD) and 13.2 mSv (finger dose).
      Extrapolated annual WBDs and finger doses (25 I-labelled lipiodol treatments per
      year) for radiologists were estimated to 165 microSv and 3.8 microSv,
      respectively. CONCLUSION: Fortunately, these doses were always lower than the
      limits reported in the European Directive EURATOM 96/29 05/13/1996 (WBD <20
      mSv.year; finger dose: 500 mSv.year) but have to be added to those relative to
      other metabolic radiotherapies such as radioiodine treatments and new metabolic
      radiotherapies (Y-conjugated peptides or antibodies). Nevertheless, the global
      exposure of medical staff involved in all these clinical practices justifies
      dosimetry studies to validate protocols and radiation protection devices for each
      institution.

PMID- 18317309
TI  - The open-door policy: good or bad for whom?
AB  - Many new nursing leaders assuming deanships, assistant, or interim deanships have
      limited education, experience, or background to prepare them for the job. To
      assist new deans and those aspiring to be deans, the authors of this department,
      2 deans, offer survival tips based on their personal experiences and insights.
      They address common issues, challenges, and opportunities that face academic
      executive teams, such as negotiating an executive contract, obtaining faculty
      lines, building effective work teams, managing difficult employees, and creating
      nimble organizational structure to respond to changing consumer, healthcare
      delivery, and community needs. The authors welcome counterpoint discussions with
      readers.

PMID- 18317310
TI  - Sampling the sample.

PMID- 18317311
TI  - Assuring the success of part-time faculty.

PMID- 18317312
TI  - A rubric for grading or editing student papers.

PMID- 18317313
TI  - Nursing student employment: impact on academic achievement.

PMID- 18317314
TI  - Strategies for using assigned reading in nursing courses.

PMID- 18317315
TI  - Unexpected pediatric death: a classroom experience.

PMID- 18317316
TI  - Formalized new-faculty orientation programs: necessity or luxury?
AB  - Formalized new-faculty orientation programs are not a luxury but rather a crucial
      necessity to recruit and retain competent and qualified faculty. The author
      describes the contents of what might be contained in such a program. Specific
      educational purposes and their link to mission, vision, and values are discussed.
      Selection of topics and objectives will also be explored, along with learning
      experiences, program organization, and outcome evaluation.

PMID- 18317317
TI  - Cultivating caring through caring group and ropes course experiences.
AB  - Caring group and ropes course experiences were integrated into the first semester
      of an upper-division baccalaureate nursing curriculum to help students learn
      caring and teamwork. The authors discuss their teaching strategies and outcomes
      that promoted caring, group cohesion, closeness, trust, teamwork, and support
      among nursing students.

PMID- 18317318
TI  - Immersion in China: lessons learned.
AB  - Students can learn a great deal from international experiences. Although one can
      learn about another culture from books and discussions, immersing oneself in a
      culture tends to have a greater impact on both intended and incidental learning.
      The authors describe the lessons learned and student outcomes during a faculty
      led 5-week immersion trip to China.

PMID- 18317319
TI  - A strategy for learning principles and elements of informed consent.
AB  - Nurses frequently provide potential study participants with informed consent
      forms and information regarding involvement in research studies However, there is
      little information in the nursing literature that emphasizes how to evaluate
      informed consent documents for appropriateness. The authors present an
      instructional project for critiquing informed consent documents for content,
      clarity, readability, and conciseness.

PMID- 18317320
TI  - An academic fairy tale: a metaphor of the work-role transition from clinician to
      academician.
AB  - The author relates the findings of a qualitative study of the work-role
      transition of a clinical expert to novice nurse educator in a baccalaureate
      program. The information is presented in the form of a metaphor to provide a
      figurative way of reading research that can serve to stimulate thinking about the
      phenomenon while using storytelling to pique interest.

PMID- 18317321
TI  - Visual tracking strategies to move scholarship forward.
AB  - Moving from the doctoral student role to the faculty member role is a challenging
      transition. Strategies that motivate and help keep scholarship moving forward can
      be invaluable in helping make the transition successful. The authors discuss 2
      visual tracking strategies to promote the forward movement of scholarship. A
      whiteboard (dry erase) and a publication trajectory table to track manuscript and
      research ideas through grant proposal and manuscript submission to publication
      are described.

PMID- 18317322
TI  - Promoting self-confidence in clinical nursing students.
AB  - Clinical nursing instructors are continually telling their students that they
      just need more confidence. But how do students find this needed confidence and
      how can nursing instructors help them? The author discusses sources and
      principles of confidence in relationship to teaching behaviors and strategies for
      increasing self-confidence, such as simulations, peer modeling, story telling,
      skill review sessions, and journaling.

PMID- 18317323
TI  - Look before you leap: lessons learned when introducing clinical simulation.
AB  - Before investing in a human patient simulator, we designed a preliminary study
      that examined student responses to a laboratory exercise that used lower-fidelity
      simulation. Our purpose was to compare beginning-level, baccalaureate nursing
      students' self-reported assessment in the domains of confidence, ability, stress,
      and critical thinking before and after they participated in the simulation.
      Results showed statistically significant improvement in all domains for skills in
      urinary catheterization, intravenous and nasogastric medication administration,
      and sterile dressing change.

PMID- 18317324
TI  - Organizational achievements in glaucoma care and research.

PMID- 18317325
TI  - The Optometric Glaucoma Society (OGS).

PMID- 18317328
TI  - Descemet stripping and automated endothelial keratoplasty: an alternative to
      penetrating keratoplasty.
AB  - PURPOSE: To discuss Descemet stripping and automated endothelial keratoplasty
      (DSAEK) as an alternative to penetrating keratoplasty (PK), and to review the
      evolution of endothelial keratoplasty (EK) for endothelial dysfunction. METHODS:
      The endothelium of the right eye was removed through a 5-mm limbal incision and
      was replaced with a prepared donor endothelium that included posterior stromal
      tissue. RESULTS: After DSAEK, the patient's vision improved more rapidly and
      remained more stable than is typical for patients undergoing PK. CONCLUSION:
      DSAEK provides an alternative both to PK and to a repeat PK in patients with
      failed grafts because of endothelial cell dysfunction. The advantages DSAEK
      surgery can offer are a quicker visual recovery, a more stable refraction, a
      tectonically more stable globe, and fewer ocular surface defects associated with
      corneal sutures or the surface graft host interface. The limitations associated
      with DSAEK include donor button dislocation and endothelial cell loss and
      dysfunction. Whether DSAEK or PK offers the best visual outcome and graft
      survival over the long term is unknown. Caution is advised until multicenter
      trials confirm the optimal procedure.

PMID- 18317329
TI  - An improved low order method for corneal reconstruction.
AB  - PURPOSE: An iterative and cubic arc-step method for corneal reconstruction
      developed previously, was retested including improved skew-ray compensation. The
      method was compared with a similar method described by Klein, and also with a
      least squares based approach using Zernike polynomials. METHODS: Images of an
      asphere, a cornea after photorefractive keratectomy (PRK), an ellipsoid and
      radially keratotomized (RK) cornea were generated. Three reconstruction methods
      were applied: (i) the cubic method (without skew-ray compensation; with old and
      improved compensation), (ii) the method due to Klein and (iii) a least squares
      approach based on Zernike polynomials (order taken up to 25). Errors were
      recorded for all conditions tested. RESULTS: The root mean square errors for the
      improved method were well below micron level, and consistently lower than the
      method of Klein. The Zernike-based method produced lowest errors for aspheric and
      ellipsoidal surfaces, when order was > or =(10, 8) respectively. However, the
      improved method produced the lowest errors for the PRK and RK examples. In this
      case, the Zernike-based method produced submicron errors for orders > or =14
      (both surfaces), but errors comparable with the arc-step methods could not be
      achieved for polynomial orders < or =25. The improved method completed in three
      to four iterations (abs. height error <1 x 10(-7) mm) in all cases. CONCLUSIONS:
      Compensation for skew-rays was incorporated in a straightforward way, yielding an
      efficient and effective low-order method. The Zernike method produced the lowest
      root mean square errors for asphere and ellipsoid, provided order was > or =(10,
      8). However, the arc-step methods (the cubic and Klein methods) were more
      accurate for RK and PRK surfaces, at least for Zernike orders < or =25. The
      results suggest that low order methods provide a good solution to the
      reconstruction of corneal shape, at least for Placido disk videokeratography
      applications.

PMID- 18317330
TI  - Stereoacuity testability in African-American and Hispanic pre-school children.
AB  - PURPOSE: To determine testability using the Randot Pre-school Stereoacuity Test
      in black and Hispanic children 30 to 72 months of age. METHODS: A population
      based cohort of children 30 to 72 months of age was administered the Randot Pre
      school Stereoacuity Test, with presenting refractive correction, and before cover
      testing, visual acuity testing, or refraction. Children who could not point to
      specified two-dimensional demonstration pictures, and children who would not try
      to name or match random dot figures to the corresponding two-dimensional
      pictures, were classified as unable to perform the test. Children who were able
      to perform the task but could not correctly identify at least two 800-arcsecond
      random dot figures were classified as having no stereopsis, and were retested by
      another examiner. RESULTS: Stereoacuity testing was attempted in 1662 Hispanic
      and 1470 black children. Overall, 80% of children were able to be tested; 33% of
      children 30 to 36 months of age, 73% of children 37 to 48 months of age, 96% of
      children 49 to 60 months of age, and 98% of children 61 to 72 months of age were
      testable. Older children were significantly more likely to complete testing
      successfully than younger children (p < 0.0001). After adjusting for age, there
      was no significant ethnicity-related difference in testability (p = 0.19);
      however, there was a small but significant gender-related difference (p = 0.0002)
      with more girls (82%) than boys (77%) able to complete testing. CONCLUSIONS:
      Eighty percent of children aged 30 to 72 months can be tested using the Randot
      Pre-school Stereoacuity test. Testability increases steadily with age, and 97% of
      children over 48 months of age can complete the test. Testability does not differ
      between children of Hispanic and black ethnicity.

PMID- 18317331
TI  - The effects of interocular correlation and contrast on stereoscopic depth
      magnitude estimation.
AB  - PURPOSE: Decreasing the interocular correlation in random dot stereograms
      elevates disparity detection thresholds. Whether decorrelation also affects
      perceived depth from suprathreshold disparity magnitudes is unknown. The present
      study investigated the effects of interocular correlation and contrast on the
      magnitude of perceived depth in suprathreshold random dot stereograms. METHODS:
      Stereoscopic depth magnitude estimation as a function of percent interocular
      correlation of dynamic random dot stimuli was measured for five human subjects
      with clinically normal binocular vision. Each trial's stimulus was randomly
      assigned one of two magnitudes of either crossed or uncrossed relative disparity.
      Subjects verbally reported the direction and magnitude of perceived relative
      depth for each trial using a modulus-free scale. Normalized depth magnitude
      estimations as a function of the percent interocular correlation demonstrated the
      relationship between perceived depth, interocular correlation and contrast within
      subjects. Inter-subject variability was examined with comparisons of data across
      subjects. RESULTS: The depth magnitude perceived for a given magnitude of
      disparity declined as the percent of correlation of elements between the eyes
      decreased for both crossed and uncrossed directions. The effect generally was
      greater for uncrossed disparities and lower contrast. Some subjects demonstrated
      asymmetries in perceived depth for crossed vs. uncrossed disparities of the same
      magnitude. CONCLUSIONS: Magnitude estimation of suprathreshold stimuli provided a
      method of studying performance characteristics of stereoscopic depth perception
      across the range of functional disparities. Differences found in depth magnitude
      estimation as a function of the sign of disparity suggest that the neural
      mechanisms underlying depth perception from uncrossed disparity are more
      sensitive to image decorrelation, particularly at low contrast, than the
      mechanisms underlying depth estimation from crossed disparity. These results
      could occur from differences in near and far disparity-sensitive neurons, from
      the geometrical relationship between disparity and physical distance in normal
      viewing, or from the response measure independent of perception.

PMID- 18317332
TI  - Interocular differences in higher-order aberrations on binocular visual
      performance.
AB  - PURPOSE: To analyze the influence of higher-order aberrations on binocular visual
      performance under mesopic conditions. METHODS: We measured aberrations in both
      eyes of 35 emmetropic observers with a Wasca aberrometer. Binocular visual
      performance was checked with both binocular summation for contrast sensitivity
      function and a parameter that characterizes stereopsis (maximum disparity).
      RESULTS: Binocular summation and maximum disparity significantly decrease with
      increasing interocular differences in higher-order aberrations (total, coma, and
      spherical aberration). CONCLUSIONS: At least some aspects of binocular visual
      performance are less effective for large interocular differences in higher-order
      eye aberrations.

PMID- 18317333
TI  - ERGs and psychophysical thresholds in students with reading discomfort.
AB  - PURPOSE: Symptoms of reading discomfort include unpleasant somatic and perceptual
      effects, such as eye-strain, headache, and blurred text, despite normal visual
      acuity. Reading discomfort has been proposed to be the result of increased noise
      in the visual system. Several studies have suggested that the symptoms can be
      minimized by having the subject wear colored filters. Thus, there may be abnormal
      neural processing in the cone pathways. This study measured L- and M-cone
      isolating (1) ERGs and (2) psychophysical thresholds in normal and reading
      discomfort subjects to determine if cone processing was abnormal in the reading
      discomfort population. METHODS: Twenty-two normal and nineteen reading discomfort
      college students took part in this study. The normal subjects had Conlon survey
      scores within 0.5 SD of the mean and the reading discomfort subjects had scores
      >1.5 SD above the mean. ERGs were determined for a range (5 to 15%) of L- and M
      cone contrasts. Slopes were determined for the L- and M-cone ERG amplitudes for
      each subject. Psychophysical thresholds were determined with a 2AFC technique
      combined with a 3-up and 1-down staircase procedure that terminated after 18
      reversals occurred. The threshold was calculated as the average of the last 8
      reversals. RESULTS: The average ERG slopes were not significantly different
      between the normal and reading discomfort groups (L-Cone, p = 0.086; M-Cone, p =
      0.47). The L/M cone ratios for the slopes were not significantly different (p =
      0.55). The log of the color contrast thresholds were not significantly different
      between the normal and reading discomfort groups (L-Cone, p = 0.97; M-Cone, p =
      0.92). CONCLUSIONS: L- and M- cone ERG contrast gains and psychophysical
      estimates of color contrast thresholds were not significantly different. These
      results do not support the noisy visual system hypothesis of reading discomfort.

PMID- 18317334
TI  - Divergence influences triggering of both vertical and horizontal saccades.
AB  - PURPOSE: In real life, divergence is frequently combined with vertical saccades.
      The purpose of this study was to examine the initiation of vertical and
      horizontal saccades, pure or combined with divergence. METHODS: We used a gap
      paradigm to elicit vertical or horizontal saccades (10 degrees), pure or combined
      with a predictable divergence (10 degrees). Eye movements from 12 subjects were
      recorded with EyeLink II. RESULTS: The major results were (i) when combined with
      divergence, the latency of horizontal saccades increased but not the latency of
      vertical saccades; (ii) for both vertical and horizontal saccades, a tight
      correlation between the latency of saccade and divergence was found; (iii) when
      the divergence was anticipated, the saccade was delayed. CONCLUSION: We conclude
      that the initiation of both components of combined movements is interdependent.

PMID- 18317335
TI  - C677T methylene-H4-folate-reductase variant decreases binocular accommodation.
AB  - PURPOSE: The C677T polymorphism of methylene tetrahydrofolate reductase (MTHFR)
      lowers the activity of this enzyme, producing moderate elevation of blood levels
      of homocysteine (Hcy) and lowering the levels of 5-methyl-tetrahydro-folic acid
      (5-MeTHFA), methionine (Meth), and S-adenosylmethionine (SAM). In this study we
      examined 100 apparently normal subjects of both sexes (average age 25.6 +/- 4.25)
      for the genotypic presence of the T allele and its association with accommodative
      amplitude (AA). METHODS: The amplitude of accommodation was measured by the
      subjective "push-up" technique. DNA from buccal cells was genotyped for the C677T
      polymorphism of MTHFR by a PCR-restriction fragment length polymorphism
      genotyping assay. Descriptive statistics were obtained by frequency distribution
      and univariate analysis. Comparisons between monocular and binocular AA were
      obtained by t-test statistics or ANOVA. Associations between genotype and
      phenotype were analyzed using regression models. RESULTS: The C677T polymorphism
      was associated with decreased binocular AA (p = 0.0087). Monocular AA was not
      associated with the MTHFR genotype. CONCLUSIONS: Our results suggest a role for
      the C677T polymorphism in damaging the neural aspects of binocular vergence
      accommodation. The postulated neural damage could be due to the decreased
      formation of 5-MeTHFA and the defective synthesis of Meth, SAM and
      neurotransmitters or other methyl acceptors in nervous tissue of bearers of the
      C677T polymorphism. The differential effect upon monocular and binocular
      accommodation is hypothetically explained by a greater involvement of methylation
      reactions in vergence accommodation. A similar mechanism is proposed to explain
      the prevalent insufficient accommodation of Down's syndrome in which the blood
      levels of Meth and SAM are reduced.

PMID- 18317336
TI  - Optical and visual performance of aspheric soft contact lenses.
AB  - PURPOSE: This study was conducted to investigate whether aspheric design soft
      contact lenses reduce ocular aberrations and result in better visual acuity and
      subjective appreciation of clinical performance compared with spherical soft
      contact lenses. METHODS: A unilateral, double-masked, randomized and controlled
      study was undertaken in which ocular aberrations and high and low contrast logMAR
      visual acuity were measured on myopic subjects who wore aspheric design
      (Biomedics 55 Evolution, CooperVision) and spherical design (Biomedics 55,
      CooperVision) soft contact lenses. Ten subjects who had about -2.00 D myopia wore
      -2.00 D lenses and 10 subjects who had about -5.00 D myopia wore -5.00 D lenses.
      Measurements were made under photopic and mesopic lighting conditions. Subjects
      were invited to grade comfort, vision in photopic and mesopic conditions, and
      overall impression with the two lens types on 100 unit visual analogue scales.
      RESULTS: There was no significant difference in high contrast or low contrast
      visual acuity between the two lens designs of either power under photopic or
      mesopic conditions. Both lens designs displayed lower levels of spherical
      aberration compared with the "no lens" condition under photopic and mesopic light
      levels (p < 0.0001); however, there were no differences in aberrations between
      aspheric and spherical lens designs. There were no statistically significant
      differences in subjective appreciation of clinical performance between lens
      designs or lens powers. CONCLUSIONS: At least with respect to the brand of lenses
      tested, the fitting of aspheric design soft contact lenses does not result in
      superior visual acuity, aberration control, or subjective appreciation compared
      with equivalent spherical design soft contact lenses.

PMID- 18317337
TI  - What is the real gold standard for ROP screening?

PMID- 18317338
TI  - Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in
      progressive threshold retinopathy of prematurity.
AB  - PURPOSE: To report the short term anatomic response of intravitreal bevacizumab
      (Avastin, Genentech) as salvage treatment in progressive retinopathy of
      prematurity (ROP) in a small series of patients. METHODS: The study included five
      eyes of three patients with progressive ROP despite peripheral laser ablation.
      Patients received intravitreal injections of bevacizumab (Avastin, Genentech).
      RetCam (Clarity Medical Systems, Inc., Pleasanton, CA) photography and
      ultrasonography were used to document effect. RESULTS: Three patients were
      transferred to the Bascom Palmer Eye Institute/Jackson Memorial Hospital for
      management of progressive ROP despite laser therapy at an outside facility.
      RetCam fundus photography and ultrasonography were used to document all cases.
      After informed consent was obtained from the parents, the patients received off
      label intravitreal bevacizumab as salvage treatment. Repeat intravitreal
      injections of bevacizumab were utilized in several cases. The ROP stabilized
      allowing laser supplementation. There was varying development of tractional
      retinal detachments in several of the eyes but the ROP component quieted in all
      cases. CONCLUSIONS: Off-label use of bevacizumab appears to be useful as a
      salvage treatment for ROP when laser treatment is precluded. It improves
      dilation, quiets the disease when visibility is difficult, and temporizes the
      disease until laser can be supplemented.

PMID- 18317339
TI  - Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of
      prematurity.
AB  - PURPOSE: To evaluate the role of antiangiogenic therapy with intravitreal
      bevacizumab for retinopathy of prematurity (ROP). METHODS: In this
      noncomparative, prospective, interventional case series, bevacizumab was injected
      into the vitreous of patients with ROP in three different groups: group I,
      patients with stage IVa or IVb ROP who had no response to conventional treatment;
      group II, patients with threshold ROP who were difficult to treat with
      conventional therapy because of poor visualization of the retina; and group III,
      patients with high-risk prethreshold or threshold ROP. RESULTS: Thirteen patients
      (18 eyes; mean age +/- SD, 4 +/- 3 months; mean follow-up, 6 months) were
      included in the study. We found neovascular regression in 17 eyes. One patient
      with stage IVa ROP had spontaneous retinal reattachment after an intravitreal
      injection of bevacizumab. There were no serious ocular or systemic adverse
      events. CONCLUSION: The use of bevacizumab may be promising in the treatment of
      patients with ROP. Further studies need to be performed to determine the safety
      and long-term efficacy of intravitreal injection of bevacizumab, either as first
      line therapy or after failure of conventional therapy.

PMID- 18317340
TI  - Management of retinal detachment in Coats disease. Study of 15 cases.
AB  - PURPOSE: To correlate the final outcome with the initial presentation and
      treatment in Coats disease retinal detachment. METHODS: The records of 15
      patients with retinal detachment were evaluated retrospectively regarding the age
      at the time of diagnosis, initial presentation, methods of treatment, visual and
      anatomic results, and complications. Changes in vision and retinal status were
      noted and correlated with the different methods of treatment to propose a
      therapeutic strategy. RESULTS: In 15 patients (15 eyes), with a mean follow-up of
      28 months (range, 6 months to 7 years), Coats disease was diagnosed at a mean age
      of 3.4 years (range 3 months to 15 years). Primary management was laser
      photocoagulation in seven patients, cryotherapy in two, and vitreoretinal surgery
      in six. Additional treatment was necessary in nine patients of whom six had laser
      photocoagulation, one had cryotherapy, and two had vitreoretinal surgery. Visual
      stability was achieved in 12 cases. Anatomic improvement was achieved in 12 eyes
      (3 cases of phthisis bulbi). No enucleation was ultimately necessary.
      CONCLUSIONS: Carefully selected treatment can improve almost each eye with Coats
      disease complicated by retinal detachment. Although visual outcome is poor,
      anatomic improvement or stability is the main goal of the management.

PMID- 18317341
TI  - Pediatric endophthalmitis. A 10-year consecutive series.
AB  - PURPOSE: To report the etiology, culture results, management techniques, and
      visual outcomes for pediatric endophthalmitis at Emory University for the past 10
      years. METHODS: Retrospective chart review based on a computer generated database
      of all cases of endophthalmitis occurring in patients younger than 18 years from
      1995 to 2005. RESULTS: Sixteen cases of pediatric endophthalmitis were
      identified. Ocular trauma and previous ocular surgery were the most common
      etiologies, accounting for 44% and 38% of cases respectively. Nine cases (56%)
      had positive vitreous cultures. Sixty-six percent of cases with positive vitreous
      cultures involved Gram-positive species. All patients were treated with
      intravitreal antibiotics. Primary vitrectomy was performed in nine cases.
      Subsequent to the intraocular infection, 6 eyes (38%) developed retinal
      detachments. At last follow-up, visual acuity of 20/400 or better was obtained in
      only 6 eyes (38%). CONCLUSIONS: Pediatric endophthalmitis in this series most
      commonly resulted from penetrating ocular trauma or from ocular surgery. Retinal
      detachment commonly occurred as a complication. Despite aggressive management
      with antibiotics and in many cases vitrectomy, visual outcomes were poor in this
      series.

PMID- 18317342
TI  - Combination intravitreal triamcinolone injection and cryotherapy for exudative
      retinal detachments in severe Coats disease.
AB  - Intravitreal triamcinolone injection effectively reduces subretinal fluid in
      pediatric patients with exudative retinal detachments in severe Coats disease.
      However, when combined with cryotherapy, a large percentage of patients develop
      rhegmatogenous retinal detachments with proliferative vitreoretinopathy.

PMID- 18317343
TI  - Advanced Coats' disease. Management with repetitive aggressive laser ablation
      therapy.
AB  - PURPOSE: To review the rates of globe salvage and final visual acuity outcomes
      for patients undergoing repetitive laser ablation therapy for advanced Coats'
      disease. METHODS: This study was a retrospective chart review of all patients
      diagnosed with primary Coats' disease treated on the Ocular Oncology Service of
      the Bascom Palmer Eye Institute from 1991-2006. Patients underwent repetitive
      diode laser ablation (two to nine sessions) to telangiectatic vessels and areas
      of exudative retinal detachment. Main outcome measures included ability to
      achieve globe salvage, final visual acuity, and anatomic success. RESULTS:
      Seventeen patients were identified who met all of the inclusion criteria for the
      study. All of the eyes in this study had advanced disease with some degree of
      exudation with or without a retinal detachment. The median length of follow-up
      was 10 months (mean, 21 months). The median number of laser applications required
      was 4.8 (mean, 5). Fourteen patients (82%) achieved anatomic success with
      complete resolution of the telangiectasis and exudative retinal detachments.
      Sixteen patients (94%) achieved globe salvage. The final visual acuity was
      excellent (20/20-20/50) in 7 patients (47%), moderate (20/60-20/100) in 1 patient
      (7%), and poor (worse than 20/200) in 7 patients (47%). CONCLUSION: A majority of
      patients with Coats' disease can achieve globe salvage and about half of patients
      can retain useful vision with aggressive repetitive diode laser therapy even if
      the disease is very advanced at presentation.

PMID- 18317344
TI  - Ischemic retinopathy and neovascular proliferation secondary to shaken baby
      syndrome.
AB  - BACKGROUND: Ocular lesions known to occur after shaken baby syndrome (SBS) are
      epiretinal, intraretinal, and subretinal hemorrhages, which are present in up to
      100% of patients. Retinoschisis and retinal folds have also been described. We
      describe three patients with SBS who presented with tractional retinal
      detachments secondary to neovascular proliferation and discuss the role of
      ischemia at the retinal level. PATIENTS: Three patients (two 4-month-old babies
      and one 4-year-old child) with a history of SBS in the first year of life
      presented with tractional retinal detachment due to severe preretinal
      fibrovascular proliferation. Peripheral retinal ischemia and vascular
      disorganization were noted during clinical examination. CONCLUSION: Although
      physiopathology of SBS remains disputed, ischemia has been accepted as the main
      feature of cerebral lesions. Ischemia could also be present at the retinal level
      as suggested by our patients' presentation. It could be induced by direct
      vitreous shearing of the capillary network or more probably by vascular leak due
      to brain edema and hypoxic damage of capillaries. Long-term ocular follow-up is
      necessary in SBS to treat these patients preventively.

PMID- 18317345
TI  - The photographic screening for retinopathy of prematurity study (photo-ROP).
      Primary outcomes.
AB  - PURPOSE: To evaluate the utility of remote digital fundus imaging as compared to
      indirect ophthalmoscopy to screen for retinopathy of prematurity (ROP). METHODS:
      This was a prospective, multicenter, masked clinical trial. Infants <31 weeks
      gestational age and <1000 g at birth were eligible for enrollment. Eligible
      enrolled infants were screened for ROP employing serial fundus imaging followed
      by indirect ophthalmoscopy. The main outcome measures were diagnostic
      sensitivity, specificity, positive and negative predictive values, and accuracy
      of image interpretation compared to ophthalmoscopy. RESULTS: Fifty-one infants
      (102 eyes) meeting eligibility criteria were enrolled between February 2001 and
      February 2002. Mean weekly examinations per infant (+/-SD) were 5.73 +/- 3.22
      (median 7; range 2-10). For the purposes of this study, the reading center
      established a definition of ROP seen on digital fundus images deemed sufficiently
      severe (termed clinically significant ROP, or CSROP) to warrant on-site
      examination by an ophthalmologist experienced in ROP. CSROP developed in 59 of
      102 eyes (57.8%; 31 right eyes and 28 left eyes). Of the eyes with CSROP, 22%
      (13/59; 7 right eyes and 6 left eyes) progressed to ROP severe enough to require
      treatment according to the criteria of the Early Treatment for ROP Randomized
      Trial. Using onsite indirect ophthalmoscopic diagnosis as the reference standard,
      CSROP was identified by digital images with a sensitivity of 92% (94% right eyes
      and 89% left eyes) and specificity of 37.21% (40% right eyes and 35% left eyes),
      and Early Treatment for Retinopathy of Prematurity (ETROP) prethreshold Type I
      with a sensitivity of 92% (86% right eyes and 100% left eyes) and specificity of
      67.39% (67% right eyes and 68% left eyes). CONCLUSIONS: Remote interpretation of
      digital fundus images is a useful adjunct to conventional bedside ROP screening
      by indirect ophthalmoscopy. Diagnostic sensitivity in this study was excellent.
      It was highly unlikely that severe ROP would be missed when image quality was
      high. Differences between the two screening approaches in timing of diagnosis of
      CSROP and ETROP were not statistically significant. Remote digital fundus imaging
      as deployed in this study is unlikely to supplant bedside ophthalmoscopic
      examination due to limitations in diagnostic sensitivity, specificity, and
      accuracy when image quality is poor.

PMID- 18317346
TI  - Anterior segment ischemia following laser therapy for threshold retinopathy of
      prematurity.
AB  - PURPOSE: To report on the clinical characteristics and outcomes of premature
      infants developing signs of anterior segment ischemia after laser therapy for
      threshold retinopathy of prematurity treated or referred to a university
      institution. METHODS: A retrospective review of the medical records of premature
      infants with a primary diagnosis of retinopathy of prematurity undergoing laser
      therapy for threshold disease from January 1, 2001, to June 1, 2006. RESULTS: A
      total of 10 eyes in six patients were identified that developed signs of anterior
      segment ischemia for which a 1-year follow-up was available. The mean gestational
      age of patients developing anterior segment ischemia was 26.1 weeks. The mean
      weight was 855 g. The mean gestational age when laser photoablation was initiated
      was 36.3 weeks. All infants developing ischemia were treated with intermittent
      dense laser pattern using the diode laser. No infants treated thus far with
      confluent laser pattern have developed anterior segment ischemia. CONCLUSION:
      Confluent laser pattern in our experience does not predispose to anterior segment
      ischemia. Anterior segment ischemia primarily affects premature infants less than
      28 weeks gestational age with low birthweights, less than 1,075 g. Intravitreal
      steroids at the time of pars plana vitrectomy and lensectomy may be beneficial in
      selected patients.

PMID- 18317347
TI  - Association of systemic risk factors with the progression of laser-treated
      retinopathy of prematurity to retinal detachment.
AB  - PURPOSE: To identify systemic risk factors associated with treatment failure of
      diode laser photocoagulation for threshold or prethreshold retinopathy of
      prematurity (ROP). METHODS: Consecutive infants treated with laser at our
      institution and infants referred from outside centers with progression to stage 4
      or 5 ROP after laser treatment were included in this retrospective study. Two
      groups were identified: those with regression of ROP after laser (LT group; 196
      eyes of 98 infants) and those with progression to stage 4 or 5 ROP after laser
      (ST group; 134 eyes of 80 infants). RESULTS: Using a multiple logistic regression
      model, there was a statistically significant association for progression of
      treated ROP to retinal detachment (RD) with history of sepsis (P < 0.001), oxygen
      therapy (P = 0.003), mechanical ventilation (P = 0.003), respiratory distress
      syndrome (RDS; P = 0.005), and patent ductus arteriosus (PDA; P = 0.042). On the
      other hand, jaundice (P = 0.563), anemia (P = 0.599), thrombocytopenia (P =
      0.689), and blood transfusion (P = 0.878) did not show a statistically
      significant association with failure of laser treatment and progression of ROP to
      stage 4 or 5 disease. CONCLUSIONS: Premature infants with a history sepsis,
      oxygen therapy, mechanical ventilation, RDS, and PDA may be at a higher risk for
      progression of ROP despite diode laser treatment.

PMID- 18317348
TI  - 25-gauge lens-sparing vitrectomy for stage 4A retinopathy of prematurity.
AB  - PURPOSE: To evaluate the feasibility of performing lens-sparing vitrectomies
      using 25-gauge instruments for the management of stage 4A retinal detachments in
      Retinopathy of Prematurity (ROP). METHODS: 13 eyes of 10 patients with stage 4A
      retinal detachments underwent a lens-sparing pars plicata vitrectomy. All
      patients were operated using a three port transconjunctival 25-gauge sutureless
      technique. The sclerotomies were made 0.5 to 1.0 mm posterior to the limbus
      through the pars plicata. Core vitrectomy and membrane peeling were performed. A
      partial fluid-air exchange was used at the end of the procedure in the majority
      of the cases. The anatomic status of the retina was determined by ophthalmoscopy
      during routine follow up visits or under general anesthesia. Per-operative
      complications were recorded. RESULTS: Eight of the infants were female and two
      were male. The average postmenstrual age at birth was 26.4 weeks and the average
      postgestational age at time of surgery was 39.3 weeks (range, 33-44). Three out
      of the 13 eyes (23%) had zone I ROP. With a mean follow-up of 17 months (range, 4
      36) 12 out of the 13 eyes (92%) achieved successful retinal reattachment. One eye
      developed post operative hypotony with a small choroidal detachment that resolved
      spontaneously. CONCLUSIONS: Surgical intervention with a three port 25-gauge
      transconjunctival sutureless vitrectomy is an effective technique to attach the
      retina in patients with stage 4A retinal detachment in ROP.

PMID- 18317349
TI  - Subretinal hemorrhage after lens-sparing vitrectomy in infants born at or under
      24 weeks gestation.
AB  - PURPOSE: To describe short term outcomes in a case series of infants with rapidly
      progressive retinopathy of prematurity (ROP) requiring laser and lens-sparing
      vitrectomies (LSV) at early postmenstrual ages (PMAs). METHODS: Retrospective
      chart review of infants born at or under 24 0/7 weeks consecutively referred for
      management of severe ROP between August 2006 and January 2007. RESULTS: Five
      female infants (mean gestational age 23 4/7 weeks, mean birthweight 514.4 g)
      required laser treatment bilaterally for zone 1 or posterior zone II ROP at 35-37
      weeks PMA. LSV was performed for progressive stage 4 ROP in eight eyes at 37-39
      weeks PMA (mean 38.2 weeks). Subretinal hemorrhage occurred after LSV in five
      eyes, with three developing subretinal fibrosis preventing complete retinal
      reattachment. CONCLUSION: Premature infants in this series had rapidly
      progressive ROP requiring laser and LSV at early PMAs. Subretinal hemorrhage
      occurred and may be related to the amount of laser necessary to treat large zones
      of avascular retina, and the early timing of vitrectomy when postoperative
      contracting preretinal vitreous no longer has the natural tamponading force of
      formed gel against it. Improved therapies for premature infants of very young
      gestational ages and large avascular zones are needed.

PMID- 18317350
TI  - Plasmin enzyme-assisted vitrectomy for primary and reoperated eyes with stage 5
      retinopathy of prematurity.
AB  - PURPOSE: To review the surgical outcome of plasmin enzyme-assisted vitreoretinal
      surgery in managing stage 5 retinopathy of prematurity (ROP). METHODS: A
      retrospective, consecutive interventional cases series of 80 eyes (68 patients)
      with stage 5 ROP, treated with autologous or maternal plasmin enzyme-assisted
      vitreoretinal surgery, were reviewed. All study patients underwent surgery
      between 1995 and 2004 with plasmin enzyme-assisted vitreoretinal surgery. Thirty
      eight eyes had previous vitreous surgery without retinal breaks (Group 1).
      Fifteen eyes had previous vitreous surgery with retinal breaks (Group 2). Twenty
      eyes received previous laser, and/or cryotherapy, and/or scleral buckling, but no
      vitrectomy (Group 3). Seven eyes did not receive any treatment previously (Group
      4). RESULTS: Postoperative anatomic outcome, functional results, and surgical
      complications in each group of eyes at an average follow-up of 49 months were
      recorded. Following surgery of all 80 eyes, anatomic success was achieved in
      68.8%. Six eyes (7.5%) achieved 20/60 to 20/600 vision. Fifty-nine eyes (73.8%)
      achieved vision worse than 20/600 to light perception. Eleven eyes (13.8%)
      achieved no light perception. Visual results were uncertain in 4 eyes (5%)
      because of the inability to measure reliably. CONCLUSION: Plasmin enzyme-assisted
      vitrectomy in eyes with and without previous vitrectomy surgery can achieve
      visual improvement in stage 5 ROP. Early intervention with vitreous surgery for
      stage 4A ROP will achieve better anatomic and visual results and reduce the
      number of children with stage 5 ROP.

PMID- 18317351
TI  - Treatment of vascularly active familial exudative vitreoretinopathy with
      pegaptanib sodium (Macugen).
AB  - PURPOSE: To report results of treatment of vascularly active familial exudative
      vitreoretinopathy (FEVR) with pegaptanib sodium (Macugen; Eyetech
      Pharmaceuticals, New York, NY) injection. METHODS: In a retrospective case
      series, four patients with vascularly active FEVR, as demonstrated by increasing
      subretinal exudation despite photocoagulation, cryotherapy, and/or intravitreal
      steroid injection, received a single intravitreal injection of pegaptanib sodium.
      Preinjection and postinjection fundus photography, fluorescein angiography, and
      optical coherence tomography were performed to evaluate the changes in visual
      acuity, vascular activity, and amount of exudation. RESULTS: The mean follow-up
      period was 11.2 months (range, 8.1-15.5 months) after the first intravitreal
      injection. All four patients had a decrease in exudation after treatment with
      pegaptanib sodium documented by a decrease in subretinal exudate by fundus
      photography and decreased leakage by fluorescein angiography. After reduction of
      exudation, two patients required vitrectomy to relieve vitreoretinal traction.
      Visual acuity improved in two patients, stabilized in one patient, and worsened
      in one patient secondary to tractional retinal detachment. No injection
      associated systemic or ocular complications were observed in any of the treated
      patients. CONCLUSIONS: Intravitreal injection of pegaptanib sodium is a potential
      treatment option for patients with FEVR and worsening exudation despite treatment
      with standard therapy. Vitreoretinal traction may develop with rapid resolution
      of subretinal exudates, requiring surgical intervention. However, visual acuity
      can improve after retinal traction is released. Further studies using anti
      vascular endothelial growth factor agents are needed to better understand
      treatment of FEVR.

PMID- 18317352
TI  - Heterogeneous tumor vasculature in retinoblastoma: implications for vessel
      targeting therapy.
AB  - PURPOSE: The aim of this study is to correlate tumor size of retinoblastoma tumor
      samples with blood vessel maturation to assess how these factors may affect
      vessel targeting therapy. METHODS: Analysis was performed on retinoblastoma tumor
      specimens (n = 5) enucleated as primary treatment from May 2005 to February 2006.
      Tumor size was measured as the largest cross sectional area of the tumor,
      measured during pathologic assessment. Vessel density and heterogeneity was
      measured by immunohistochemical analysis. Total microvessel density was detected
      by staining endothelial cells using a lectin from Bandeira simplicifolia; novel
      vasculature was detected with the endothelial cell marker endoglin (CD105). Blood
      vessel basement membrane was detected with an antibody against type IV collagen.
      Vessel maturation was assessed by pericyte recruitment, detected with alpha
      smooth muscle actin (alpha-sma). RESULTS: A statistically significant correlation
      was detected between tumor burden and age at enucleation (P = 0.008). All
      retinoblastoma tumor samples harbored a high degree of blood vessel heterogeneity
      containing both immature neovessels as well as pericyte-committed mature
      vasculature. There was a statistically significant correlation between type IV
      collagen and age at enucleation (P = 0.045). CONCLUSIONS: This study provides a
      framework for a better understanding of tumor and vessel development in
      retinoblastoma. Results of this study provide insight into the relationship
      between age and tumor burden in these tumors. Knowledge of the degree of
      heterogeneity detected in these tumors will aid in the selection of novel blood
      vessel targeting strategies for children with this disease and other diseases
      with pathologic neovascularization.

PMID- 18317354
TI  - Chromosome mechanisms giving rise to the TMPRSS2-ERG fusion oncogene in prostate
      cancer and HGPIN lesions.

PMID- 18317355
TI  - Traumatic neuroma of the bronchi: bronchoscopy and histology of a hitherto
      unreported lesion.

PMID- 18317356
TI  - Chemokine receptors expression and migration potential of tumor-infiltrating and
      peripheral-expanded Vgamma9Vdelta2 T cells from renal cell carcinoma patients.
AB  - We previously showed that Vdelta2 T cells infiltrate renal tumors and can be
      expanded as potent cytotoxic effectors from peripheral blood mononuclear cells of
      most renal cell carcinoma (RCC) patients, using a structural analog of
      nonconventional T-cell receptor gamma9delta2 ligand, bromohydrin pyrophosphate,
      and interleukin-2 (IL-2). In this study, we have further investigated the
      differentiation status and the migration potential of circulating and tumor
      infiltrating Vgamma9Vdelta2 T lymphocytes from RCC patients. The repertoire of
      tumor-infiltrating and peripheral Vgamma9Vdelta2 T cells from RCC patients was
      characterized by a dominant CD27- CD45RA- subset. These effector memory
      Vgamma9Vdelta2 T cells were efficiently expanded using bromohydrin pyrophosphate
      combined with IL-15, but not IL-2. In addition, peripheral Vgamma9Vdelta2 T cells
      from RCC patients present a modified chemotactic pattern compared with donors.
      After ex vivo activation, peripheral expanded Vgamma9Vdelta2 T cells acquire low
      migration capacities toward renal cells. Tumor-infiltrating Vgamma9Vdelta2 T
      cells migrated with higher efficiency toward primary renal tumor cells. The
      traffic toward tumor cells required the CXCL12/CXCR4 interaction. Altogether,
      these results outline that those Vgamma9Vdelta2 effectors exhibit differential
      migration capacities according to their localization, their differentiation
      status, and the tumor microenvironment parameters that may influence their use in
      immunotherapy.

PMID- 18317357
TI  - Anti-idiotypic Immunotherapy in follicular lymphoma patients: results of a long
      follow-up study.
AB  - A specific immune response against the individual idiotypic determinants of
      clonal immunoglobulins can be elicited in patients with B-cell malignancies. We
      analyze the clinical outcome and the presence of tumor cells in the blood of 8
      patients with follicular lymphoma, vaccinated with autologous idiotype protein
      from their lymphoma cells. After a median follow-up of 90 months (range: 54 to
      128), all patients, except 1, remain in complete clinical remission and 5 are in
      complete molecular remission. Our results suggest that idiotype vaccination
      induces long-lasting clinical and molecular remissions and constitutes a
      potential curative treatment in follicular lymphoma patients.

PMID- 18317358
TI  - Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic
      melanoma.
AB  - We performed a phase 1/2 trial testing the safety, toxicity, and immune response
      of a vaccine consisting of autologous dendritic cells (DCs) transduced with a
      replication-defective adenovirus (AdV) encoding the full-length melanoma antigen
      MART-1/Melan-A (MART-1). This vaccine was designed to activate MART-1-specific
      CD+8 and CD4+ T cells. Metastatic melanoma patients received 3 injections of
      10(6) or 10(7) DCs, delivered intradermally. Cell surface phenotype and cytokine
      production of the DCs used for the vaccines were tested, and indicated
      intermediate maturity. CD8+ T-cell responses to MART-1 27-35 were assessed by
      both major histocompatibility complex class I tetramer and interferon (IFN)-gamma
      enzyme-linked immunosorbent spot (ELISPOT) before, during, and after each vaccine
      and CD4+ T-cell responses to MART-1 51-73 were followed by IFN-gamma ELISPOT. We
      also measured antigen response breadth. Determinant spreading from the immunizing
      antigen MART-1 to other melanoma antigens [gp100, tyrosinase, human melanoma
      antigen-A3 (MAGE-A3)] was assessed by IFN-gamma ELISPOT. Twenty-three patients
      were enrolled and 14 patients received all 3 scheduled DC vaccines. Significant
      CD8+ and/or CD4+ MART-1-specific T-cell responses were observed in 6/11 and 2/4
      patients evaluated, respectively, indicating that the E1-deleted adenovirus
      encoding the cDNA for MART-1/Melan-A (AdVMART1)/DC vaccine activated both helper
      and killer T cells in vivo. Responses in CD8+ and CD4+ T cells to additional
      antigens were noted in 2 patients. The AdVMART1-transduced DC vaccine was safe
      and immunogenic in patients with metastatic melanoma.

PMID- 18317359
TI  - Effect of frequently used chemotherapeutic drugs on cytotoxic activity of human
      cytotoxic T-lymphocytes.
AB  - Tumors are considered to be possible targets of immunotherapy using stimulated
      and expanded cytotoxic T-lymphocytes (CTL). It is important to consider the drug
      induced effects when chemotherapeutic regimens and CTL-mediated immunotherapy is
      planned to be used in parallel. In this study, we characterized the effect of 29
      frequently used chemotherapeutic agents on the cytotoxic activity of autologous
      and allogeneic CTLs. We found that treatment of CTLs with the following drugs:
      docetaxel, vincristine, chlorambucil, mitomycin C, oxaliplatin, doxorubicin, and
      bleomycin effectively inhibited CTL-mediated killing, without affecting their
      viability. On the other hand, the following drugs enhanced or permitted efficient
      CTL-mediated killing in vitro at concentrations comparable with the maximally
      achieved therapeutic concentration in vivo in humans: daunorubicin, prednisolone,
      vinorelbine, cisplatin, methotrexate, hydroxyurea, cytarabine, cyclophosphamide,
      topotecan, epirubicin, fluorouracil, carboplatin, asparaginase, 6-mercaptopurine,
      and bortezomib. Our results could potentially be used in the future to design new
      CTL-based adjuvant immunotherapy protocols.

PMID- 18317360
TI  - Increased immunostimulatory activity conferred to antigen-presenting cells by
      exposure to antigen extract from hepatocellular carcinoma after radiofrequency
      thermal ablation.
AB  - Radiofrequency thermal ablation represents an effective treatment for
      hepatocellular carcinoma (HCC) and it can also exert an "adjuvant" effect on
      spontaneous antitumor T-cell responses, as suggested by human and animal studies.
      The adjuvant effect is thought to depend on the huge amount of necrotic tumor
      antigen made available to the immune system by HCC thermal ablation. In addition,
      radiofrequency thermal ablation may result in the release of local stimuli
      responsible for activation and maturation of antigen-presenting cells (APCs). To
      test this hypothesis, we studied APC maturation and function in 19 patients
      undergoing thermal ablation for HCC. Patients' monocytes induced to differentiate
      with granulocyte macrophage colony-stimulating factor (GM-CSF), or GM-CSF plus IL
      4, were cocultured in vitro with tumor debris generated by radiofrequency thermal
      ablation. Expression of costimulatory molecules, lymphnode homing chemokine
      receptor, antigen presentation, and cytokine secretion were enhanced by
      incubation with HCC treated tissue as compared with untreated HCC and nontumor
      liver tissue. Moreover, HCC-specific T-cell responses could be induced by
      monocytes activated with GM-CSF and incubated with thermally ablated HCC tissue.
      HCC thermal ablation can create an antigenic source along with stimuli
      appropriate for maturation of APCs to induce HCC-specific T-cell responses. These
      results contribute to explain at least in part the adjuvant effect of HCC thermal
      ablation and suggest a novel strategy to induce maturation of APCs and their
      loading with HCC antigens for active immunotherapy protocols aimed at reducing
      HCC recurrence after thermal ablation.

PMID- 18317361
TI  - Adrenergic modulation of dendritic cell cancer vaccine in a mouse model: role of
      dendritic cell maturation.
AB  - The aim of the present study was to evaluate the role of beta2-adrenergic
      receptors (beta2-ARs) in the outcome of a dendritic cell (DC)-based cancer
      vaccine in the murine E.G7-ovalbumin (OVA) model. We found that unlike the beta2
      AR expressed on antigen loaded DCs, beta2-ARs expressed in the site of DCs
      inoculation may influence the efficacy of the antitumor response. Intradermal
      injection of Staphylococcus aureus peptidoglycan along with the beta2-AR-specific
      antagonist ICI 118,551 increased the local innate cytokine response in tumor
      bearing mice. When the adoptive transfer of immature DCs loaded with OVA followed
      this skin preconditioning, the antitumor response was increased and tumor growth
      was significantly reduced. Surprisingly, when OVA-loaded mature DCs were used,
      the effect of the skin preconditioning was the opposite and tumor growth was
      similar to that observed in control, nonimmunized mice. The extent of the
      antitumor response on transfer of immature or mature DCs was mediated by a
      different migration in the draining lymph nodes and by a distinct recruitment of
      endogenous DCs that resulted in a modulation of the OVA-specific cytotoxic T
      lymphocyte response. The unexpected tolerogenic effect exerted by mature DCs on
      skin preconditioning was apparently mediated by the expression of a distinctive
      pattern of cytokines and of the suppressive enzyme indoleamine 2, 3-dioxygenase
      in draining lymph nodes. In conclusion, we found that beta2-ARs inhibition along
      with toll-like receptor2 activation at the site of cancer vaccination may either
      enhance the resulting antitumor response or be tolerogenic in dependence of the
      maturation state of the transferred DCs.

PMID- 18317362
TI  - Interferon-alpha (IFN-alpha)-conditioned DC preferentially stimulate type-1 and
      limit Treg-type in vitro T-cell responses from RCC patients.
AB  - Dendritic cells (DCs) are potent antigen presenting cells and represent
      attractive candidates for use in novel immunotherapies for patients with renal
      cell carcinoma (RCC), a disease that has proven refractory to conventional
      treatment modalities, such as chemotherapy and radiotherapy. Given the perceived
      need to augment antitumor type-1 immunity (TC1 and Th1) as a therapeutic end
      point, and the known functional plasticity of DC populations that may display
      heterogeneous capacity to promote T-cell responses, we sought to identify a
      preferred DC preparation with this capacity. We compared 2 different preparations
      of monocyte-derived DC using interferon-alpha (IFN-alpha) (IFN-DC and alphaDC1)
      with classic DCs "matured" (mDCs) using interleukin-1beta/interleukin-6/tumor
      necrosis factor-alpha/prostaglandin E2, for their ability to promote autologous
      TC1 antitumor responses from RCC patients in vitro. IFN-alpha-conditioned DC
      promoted significantly higher numbers of RCC-specific CD8+ T cells exhibiting a
      cytotoxic phenotype after in vitro stimulation (IVS) than cytokine cocktail-mDCs.
      Furthermore, IVS using IFN-DCs was able to diminish regulatory-type T cells among
      CD4+ T-cell responder populations versus IVS using conventional mDC-based
      vaccines. These data emphasize an important role for IFN-alpha in modulating the
      immunologic functions of DCs toward a polarized DC1-type capable of coordinately
      promoting TH1-type and TC1-type T-cell mediated immunity and supports the
      translational development of patient-derived IFN-alpha-conditioned DC for use in
      novel immunotherapies for patients with RCC, and in whom, endogenous tumor
      specific TC1 effector cells may be dysfunctional, anergic, or prone to undergo
      apoptosis.

PMID- 18317363
TI  - Detection, isolation, and characterization of alpha-fetoprotein-specific T cell
      populations and clones using MHC class I multimer magnetic sorting.
AB  - alpha-fetoprotein (AFP) is a fetal protein specifically reexpressed in 50% of
      hepatocellular carcinomas. This protein could serve as a tumor-associated antigen
      for immunotherapy purpose. The aim of our work was to analyze the presence of AFP
      specific T cell populations in peripheral blood mononuclear cells (PBMCs) from
      cirrhotic patients with or without hepatocellular carcinoma. Using peptide-major
      histocompatibility complex class I multimers, AFP-specific populations
      corresponding to 3 previously described human leukocyte antigen (HLA)-A*0201
      major histocompatibility complex class I epitopes (AFP137, AFP158, and AFP325)
      were sorted magnetically from CD8 positive cells without prior stimulation with
      the target antigen. T cell populations specific for 1 peptide (AFP158) were
      frequent, whereas populations corresponding to peptide AFP137 were rare and
      absent for peptide AFP325. We also isolated and fully characterized T cell clones
      specific for AFP137 and AFP158 peptides. We show that these clones can be used to
      monitor dendritic cell loading with peptides and could be useful for future
      immunotherapy protocols.

PMID- 18317364
TI  - Fc-mOX40L fusion protein produces complete remission and enhanced survival in 2
      murine tumor models.
AB  - OX40L is a member of the tumor necrosis factor superfamily that provides a
      costimulatory signal to CD4+ and CD8+ T cells while inhibiting the effects of
      suppressive CD4+ CD25+ regulatory T cells. Because of this dual activity, OX40L
      may provide significant antitumor immunity in tumor-bearing mice. To study its
      clinical potential, a fusion protein consisting of mOX40L linked to the C
      terminus of the Fc fragment of immunoglobulin was genetically engineered. After
      demonstrating its potency in vitro, several assays were performed to evaluate its
      antitumor effect in comparison to the OX40 agonist antibody OX86. Dosing studies
      in Colon 26-bearing and renal cell carcinoma (RENCA)-bearing mice showed that
      although OX86 produced modest tumor regression, Fc-mOX40L produced complete
      remission in both tumor models. Survival studies confirmed these results and
      showed that Fc-mOX40L treatment produced lasting responses throughout the 5-month
      observation period. Flow cytometric analysis of treated and untreated tumors and
      tumor-draining lymph nodes identified a qualitative difference in the activity of
      Fc-mOX40L compared with OX86 treatment as evidenced by differences in lymphoid
      and macrophage populations. These studies reflect the profound therapeutic
      potential of Fc-mOX40L, which substantially exceeds the agonist antibody OX86 in
      ability to produce complete tumor remissions and promote long-term survival in
      solid tumor models.

PMID- 18317365
TI  - A humanized tumor necrosis factor receptor 1 (TNFR1)-specific antagonistic
      antibody for selective inhibition of tumor necrosis factor (TNF) action.
AB  - Tumor necrosis factor (TNF) is a recognized pathogenic mediator in a number of
      chronic and acute inflammatory diseases. Antibodies targeting TNF have
      significantly improved therapy of chronic inflammatory diseases, in particular
      rheumatoid arthritis. Despite this success, anti-TNF treatment shows clinical
      efficacy only in part of the patients and is often transient, necessitating the
      development of alternative reagents to combat TNF action. We here describe
      humanization and functional properties of a TNFR1-specific, monovalent antibody
      fragment, designated IZI-06.1, which binds to the cysteine-rich domain 1 of TNFR1
      with high affinity and competes ligand binding. IZI-06.1 serves as a receptor
      selective inhibitor of proapoptotic and antiapoptotic TNF actions, revealed from
      complete blockage of TNFR1-dependent apoptosis and interleukin-6 induction in Kym
      1 and HeLa cells, respectively, whereas TNFR2-mediated signals remained intact,
      evident from TNF and interleukin-2-mediated costimulation of interferon-gamma
      production in T cells. Accordingly, IZI-06.1 is a TNFR1-selective TNF antagonist
      and holds great promise to be developed into a clinically applicable therapeutic.
      IZI-06.1 could be a useful therapeutic alternative in all diseases already known
      to clinically respond to anti-TNF treatment and particularly in those diseases,
      where anti-TNF treatment has failed because of complete blockade of TNF action.

PMID- 18317366
TI  - Measuring activity in children and adolescents using self-report: PAQ-C and PAQ
      A.
AB  - PURPOSE: This study examined the psychometric properties of two versions of a
      commonly used physical activity 7-d self-report, the Physical Activity
      Questionnaire for Older Children (PAQ-C) and Physical Activity Questionnaire for
      Adolescents (PAQ-A). METHODS: We longitudinally examined the internal
      consistency, stability, and situational effects of the PAQ-C and PAQ-A in a
      cohort of children (N = 210) at ages 11 and 13 yr. Statistical analysis included
      factor loading and standardized Cronbach coefficient alphas. We cross-sectionally
      examined concurrent validity of the PAQ-A in a subsample of our cohort (N = 49)
      at age 13 by comparing it with concurrently measured physical activity using an
      activity monitor (Actigraph). Spearman correlation coefficients were used for
      this analysis. RESULTS: Standardized Cronbach alphas ranged from 0.72 to 0.88. A
      subsample analysis suggested that completing the questionnaires during the summer
      months slightly reduced the standardized alpha for the PAQ-C, but not the PAQ-A.
      Associations between the PAQ-A (revised) summary score and activity monitor
      variables were rho = 0.56 for total PA and rho = 0.63 for moderate through
      vigorous activity (P < 0.05). Associations between individual PAQ-A questions and
      activity monitor variables for the same time frame ranged from rho = 0.41 to 0.62
      (P < 0.05). CONCLUSION: The PAQ-C and PAQ-A show good internal consistency. The
      PAQ-A has acceptable validity.

PMID- 18317367
TI  - Validity of the CALER and OMNI-bike ratings of perceived exertion.
AB  - PURPOSE: To test the validity of the Cart and Load Effort Rating (CALER) and OMNI
      bike RPE scales. METHODS: Children (16 boys aged 9.5 +/- 0.7 and 16 girls aged
      9.4 +/- 0.8) performed a progressive exercise test on a cycle ergometer to
      exhaustion. Random effects models and correlation analysis were used to determine
      the association of the undifferentiated perceived exertion from the CALER and
      OMNI bike scales with heart rate and V O2 for concurrent validity and the
      association of the CALER scale with the validated OMNI bike scale for construct
      validity. Tests of proportions were performed to compare the proportion of
      maximal RPE scale (CALER, OMNI bike) with the proportion of maximal heart rate
      achieved during the final stage of the exercise test. RESULTS: Concurrent
      validity of the CALER and OMNI bike scales was established, as increases in
      scores of both scales were associated with (P < or = 0.001 regression) increases
      in heart rate (r = 0.88 and 0.89) and V O2 (r = 0.92 and 0.93). Construct
      validity of the CALER scale was established through a significant (P < or = 0.001
      regression) relationship with the OMNI bike scale (r = 0.93). The proportion of
      maximal CALER (75 +/- 20%) and OMNI bike (74 +/- 19%) scales were less (P < or =
      0.001) than the peak percentage of the predicted maximal heart rate (94.5 +/-
      3%). CONCLUSIONS: Validity for both the CALER and OMNI bike RPE scales was
      established for a progressively increasing exercise paradigm. However, the
      proportion of maximal perceived exertion scores from both scales was lower than
      the proportion of predicted maximal heart rate achieved during the final stage of
      the exercise test.

PMID- 18317368
TI  - Visuomotor expertise and dimensional complexity of cerebral cortical activity.
AB  - PURPOSE: This study employed the correlation dimension (D2) to examine whether
      visuomotor expertise was inversely related to the complexity of cerebral cortical
      activity. METHOD: Expert rifle shooters (N = 15) and novices (N = 21) completed
      40 shots in the standing position during which the electroencephalogram (EEG) was
      recorded at 10 sites (F3, F4, C3, C4, T3, T4, P3, P4, O1, and O2) during a 5-s
      aiming period prior to trigger pull. D2 was derived for each trial and averaged
      across shots. A 2 x 2 x 5 (group x cerebral hemisphere x region) ANOVA was
      employed to contrast D2, while correlation analyses were used to determine the
      relationship between D2 and target shooting accuracy as well as variability of
      shot placement. RESULTS: As predicted, experts exhibited lower D2 (5.02 +/- 0.16
      vs 5.49 +/- 0.13, respectively) and greater accuracy of shot placement ((339.8 +/
      44.7 vs 90.7 +/- 38.9 points out of 400 possible, respectively). Experts also
      exhibited an inverse relationship between D2 and shooting accuracy, while, in
      contrast, novices revealed a positive relationship. DISCUSSION: The results
      suggest that refinement and efficiency of cerebral cortical activity facilitates
      visuomotor performance. Lower complexity may be associated with less neuromotor
      "noise" in the brain, thus reducing interference with intended action.

PMID- 18317369
TI  - Caffeine effects on short-term performance during prolonged exercise in the heat.
AB  - PURPOSE: To determine the effect of water, carbohydrate, and caffeine ingestion
      on fatigue during prolonged exercise in the heat. METHODS: Seven endurance
      trained cyclists (V O2max = 61 +/- 8 mL.kg.min) pedaled for 120 min at 63% V
      O2max in a hot-dry environment (36 degrees C; 29% humidity), ingesting either no
      fluid (NF), water (WAT) to replace 97% fluid losses, the same volume of a 6%
      carbohydrate-electrolyte solution (CES), or each of these treatments along with
      ingestion of 6 mg of caffeine per kilogram of body weight (NF + CAFF, WAT + CAFF,
      and CES + CAFF). At regular intervals during exercise, maximal cycling power
      (PMAX) was measured. Before and after exercise, maximal voluntary contraction
      (MVC), voluntary activation (VA), and electrically evoked contractile properties
      of the quadriceps were determined. RESULTS: Without fluid replacement (NF and NF
      + CAFF), subjects were dehydrated by 3.8 +/- 0.3%, and rectal temperature reached
      39.4 +/- 0.3 degrees C, while it was maintained at 38.7 +/- 0.3 degrees C in
      trials with rehydration (P < 0.05). Trials with caffeine ingestion increased PMAX
      by 3% above trials without caffeine (P < 0.05). MVC reductions after exercise
      were larger with NF (-11 +/- 5%) than for the rest of the trials (P < 0.05). MVC
      was reduced in WAT compared with CES + CAFF (-6 +/- 4 vs 2 +/- 4%; P < 0.05).
      However, NF + CAFF maintained MVC at the level of the CES trial. VA showed the
      same treatment response pattern as MVC. There were no differences in electrically
      evoked contractile properties among trials. CONCLUSION: During prolonged exercise
      in the heat, caffeine ingestion (6 mg.kg body weight) maintains MVC and increases
      PMAX despite dehydration and hyperthermia. When combined with water and
      carbohydrate, caffeine ingestion increases maximal leg force by increasing VA
      (i.e., reducing central fatigue).

PMID- 18317370
TI  - Postactivation potentiation in human knee extensors during dynamic passive
      movements.
AB  - PURPOSE: Postactivation potentiation (PAP), i.e., the increase in twitch torque
      following a maximal voluntary conditioning contraction, has been shown to depend
      on muscle contractile conditions (e.g., muscle length). Few studies, however,
      have investigated the extent of twitch PAP under dynamic conditions in human
      subjects. Therefore, the aim of the present experiment was to test the twitch PAP
      during passive dynamic movements following isometric conditioning contractions on
      nine healthy men. METHODS: Maximal twitches were evoked on the knee extensor
      muscles before and exactly 5 s after a 3-s conditioning maximal voluntary
      isometric contraction. PAP was determined at a constant joint angle under
      isometric conditions, during and immediately after passive shortening and
      lengthening with slow and fast angular velocities (30 and 150 degrees .s).
      RESULTS: Our results indicate a significant PAP increase with increasing
      shortening angular velocity (34.6 +/- 13.2% and 51.9 +/- 21.1% at 30 degrees .s
      and 150 degrees .s velocities, respectively), whereas PAP was significantly lower
      during lengthening (15.2 +/- 15.2%) as compared with isometric conditions (28.5
      +/- 18.3%). Similar results were obtained when PAP was determined isometrically
      but immediately following passive shortening or lengthening (30 degrees .s).
      CONCLUSION: These data indicate that PAP affects dynamic torque production
      capacity and that PAP is dependent on contractile conditions. Furthermore, the
      similar extent of PAP during and immediately after passive movements suggests a
      PAP history dependency. Our results therefore suggest that PAP is recommended
      more for improving shortening performance than for lengthening.

PMID- 18317371
TI  - Spinal reflex plasticity during maximal dynamic contractions after eccentric
      training.
AB  - PURPOSE: The aim of the study was to use eccentric strength training of the
      plantar flexor muscles to investigate the plasticity of the spinal reflexes
      during maximal voluntary isometric, concentric, and eccentric contractions.
      METHODS: Eighteen healthy male subjects were divided into an eccentric strength
      training group (N = 10) and a control group (N = 8). The training program
      consisted of 18 sessions of eccentric exercise for a 7-wk period. All subjects
      were tested before, during, and after the training program. Soleus (SOL) and
      medial gastrocnemius (MG) spinal reflexes (H-reflex and V-wave) and M-waves were
      evoked at the same angular position during passive isometric, concentric, and
      eccentric actions (i.e., Hmax and Mmax, respectively) and during maximal
      voluntary isometric, concentric, and eccentric plantar flexion (MVC) (i.e., Hsup,
      V-wave, and Msup, respectively). RESULTS: : Both SOL and MG Hmax/Mmax ratios
      remained unchanged whatever the action type after training. The Hsup/Msup ratio
      was increased only during eccentric MVC for the SOL (P < 0.01) and regardless of
      the contraction type for the MG (P < 0.05). The eccentric SOL Hsup/Msup ratio was
      not different from the isometric and concentric Hsup/Msup ratios after 7 wk of
      training. The V/Msup ratios were increased during isometric and eccentric
      contractions for the SOL and regardless of the contraction type for the MG after
      training. CONCLUSION: : In conclusion, the present results suggest that the
      increase in voluntary torque induced by eccentric training could be ascribed,
      according to the contraction type, to an increased volitional drive from the
      supraspinal centers, which may induce neural adaptations at the spinal level.
      Changes in the regulation of the balance between excitation and inhibition
      affecting the motoneuron pool were suggested to explain the plasticity of the
      spinal reflexes.

PMID- 18317372
TI  - Differences in EMG activity in scapular plane abduction under variable arm
      positions and loading conditions.
AB  - PURPOSE: The present study was performed to investigate the activities of four
      shoulder muscles-the supraspinatus, the middle deltoid, the infraspinatus, and
      the upper trapezius-in scapular plane abduction in various exercise conditions.
      METHODS: Eight male subjects (mean +/- SD: 23.4 +/- 1.3 yr) with an asymptomatic
      nondominant left shoulder participated in this study. Each subject performed
      scapular plane abduction with humeral external rotation (full can position) and
      with humeral internal rotation (empty can position), producing constant target
      torques of 4 and 12 N.m, respectively. In addition, the subjects performed each
      exercise in the supine position with the limb supported by straps. Electromyogram
      (EMG) was recorded with intramuscular electrodes at the supraspinatus and
      infraspinatus, and with surface electrodes placed at the middle deltoid and upper
      trapezius. The EMG activity (RMS) of each muscle was normalized according to the
      highest EMG activity (100% MVC) during a maximum manual muscle test for the
      corresponding muscle (% MVC). RESULTS: EMG activity of the supraspinatus was
      significantly greater than those of the other shoulder muscles in the full can
      position from 10-20 degrees to 50-60 degrees arcs with a target torque of 4 N.m
      (P < 0.05). In contrast, the supraspinatus and middle deltoid showed similar EMG
      activities under other exercise conditions. CONCLUSIONS: These results suggest
      that there is an exercise condition that induces greater activity of the
      supraspinatus in scapular plane abduction.

PMID- 18317373
TI  - Lower-limb mechanics during the support phase of maximum-velocity sprint running.
AB  - INTRODUCTION: The forces produced by an athlete during the support phase of a
      sprint run are a vital determinant of the outcome of the performance. The purpose
      of this study was to improve the understanding of sprint technique in well
      trained sprinters through the comprehensive analysis of joint kinetics during the
      support phase of a maximum-velocity sprint. METHODS: Four well-trained sprinters
      performed maximum-effort 60-m sprints. Two-dimensional high-speed video (200 Hz)
      and ground-reaction force (1000 Hz) data were collected at the 45-m mark.
      Horizontal velocity, step length, step frequency, and normalized moment, power,
      and work, via inverse dynamics, were calculated for two trials in each athlete.
      RESULTS: The hip extensors performed positive work in early stance (normalized
      value = 0.063 +/- 0.017), and the plantar flexors performed positive work in late
      stance (normalized value = 0.053 +/- 0.010). The knee extensors played a
      negligible role in positive work generation throughout stance. CONCLUSIONS: In
      contrast to previous findings, the knee moment did not contribute substantially
      to power generation during the latter part of the support phase. This may be
      explained in part by the specific technical requirements of the maximum-velocity
      phase of the sprint. However, major periods of power generation of the hip
      extensors in early stance and of the plantar flexors in late stance were
      observed. The action of the knee joint during the support phase may therefore
      have been more of a facilitator for the radial transfer of power from the hip
      through the ankle on to the track.

PMID- 18317374
TI  - Validity of a multisensor armband in estimating 24-h energy expenditure in
      children.
AB  - Physical activity (PA) and energy expenditure (EE) in children are frequently
      assessed using portable activity monitors. Algorithms used to predict EE by these
      monitors are often based on adult populations and may not be accurate for
      children. PURPOSE: To evaluate the accuracy of the SenseWear Pro Armband (SWA)
      for assessing EE in African American children during treadmill exercise,
      sedentary activities, rest, sleep, and total 24-h EE, using indirect room
      calorimetry (IRC) as a reference standard. METHODS: Participants were healthy
      African American children (10 boys, 11 girls; age: 11.6 +/- 0.9 yr; weight: 47.3
      +/- 13.0 kg; height: 151.6 +/- 8.8 cm; BMI: 20.4 +/- 4.8 kg.m). EE was measured
      simultaneously using IRC and SWA during a 24-h stay in the IRC. Recorded
      activities included sedentary behaviors, treadmill exercise, rest periods, and
      sleep. Results from both methods were matched minute-by-minute and compared by
      Bland-Altman plot. Multiple linear regression analysis was used to describe the
      relationship between EE assessed by both methods and children's descriptive
      characteristics. RESULTS: SWA overestimated EE compared with IRC during all
      activities and time periods, ranging from 116% during sleep to 143% during rest
      after treadmill exercise. The SWA-predicted EE was improved by using linear
      regression modeling. Simple equations for sedentary activities and treadmill
      exercise were EE [kcal.min] = 0.462EE (SWA) [kcal.min] + 0.015 x body weight
      [kg], and EE [kcal.min] = 0.637EE (SWA) [kcal.min] + 0.034 x body weight [kg],
      respectively. The prediction equation for RMR was RMR [kcal.min] = 0.453EE (SWA)
      [kcal.min] + 0.011 x body weight [kg]. CONCLUSION: EE estimated using SWA was
      significantly higher than EE measured using IRC in African American children ages
      10-14 yr. Bias in individual EE estimated using SWA could be improved by an
      adjustment for the body weight of a child. The SWA manufacturer should work with
      researchers on improving existing algorithms for children.

PMID- 18317375
TI  - Human muscle gene expression following resistance exercise and blood flow
      restriction.
AB  - INTRODUCTION: Blood flow restriction in combination with low-intensity resistance
      exercise (REFR) increases skeletal muscle size to a similar extent as compared
      with traditional high-intensity resistance exercise training. However, there are
      limited data describing the molecular adaptations that occur after REFR. PURPOSE:
      To determine whether hypoxia inducible factor-1 alpha (HIF-1alpha) and REDD1 mRNA
      are expressed differently in REFR compared with low-intensity resistance exercise
      with no blood flow restriction (CONTROL). Secondly, to determine whether low
      intensity resistance exercise is able to induce changes in mRNA expression of
      several anabolic and catabolic genes as typically seen with high-intensity
      resistance exercise. METHODS: Six subjects were studied at baseline and 3 h after
      a bout of leg resistance exercise (20% 1RM) in REFR and CONTROL subjects. Each
      subject participated in both groups, with 3 wk separating each visit. Muscle
      biopsy samples were analyzed for mRNA expression, using qRT-PCR. RESULT: Our
      primary finding was that there were no differences between CONTROL and REFR for
      any of the selected genes at 3 h after exercise (P > 0.05). However, low
      intensity resistance exercise increased HIF-1alpha, p21, MyoD, and muscle RING
      finger 1 (MuRF1) mRNA expression and decreased REDD1 and myostatin mRNA
      expression in both groups (P < 0.05). CONCLUSION: Low-intensity resistance
      exercise can alter skeletal muscle mRNA expression of several genes associated
      with muscle growth and remodeling, such as REDD1, HIF-1alpha, MyoD, MuRF1, and
      myostatin. Further, the results from REFR and CONTROL were similar, indicating
      that the changes in early postexercise gene expression were attributable to the
      low-intensity resistance exercise bout, and not blood flow restriction.

PMID- 18317376
TI  - Gender differences in brachial blood flow during fatiguing intermittent handgrip.
AB  - PURPOSE: Females have been reported to have greater resistance to skeletal muscle
      fatigue than males. Blood flow, which plays an important role in supplying oxygen
      and nutrients to working muscles, may play an important role in the mechanisms of
      gender difference. We hypothesized that females would have greater conduit artery
      blood flow supplying working muscles than males during intermittent maximal
      handgrip exercise. METHODS: Healthy adult (22-31 yr old) males (N = 8) and
      females (N = 8), lying in a supine position, repeated static maximal voluntary
      contractions (MVC) with a handgrip device in an intermittent pattern. Mean
      brachial arterial blood flow (MBABF) was continuously monitored using Doppler
      ultrasonography during the 5-s muscle-relaxation phase, when intramuscular
      pressure does not impede measurement of muscle blood flow during the 4-min
      exercise period, and continuously during the 10-min recovery period. Vascular
      conductance (VC) was calculated from the MBABF normalized by forearm volume and
      mean blood pressure (MBP). RESULTS: Females achieved higher relative muscle force
      (%MVC) than males throughout both the exercise and the recovery periods (P <
      0.05); females tended to exhibit smaller declines in muscle force (i.e., less
      fatigue). Exercise-induced increases in MBABF normalized to forearm volume were
      greater in females compared with males during the relaxation phases (P < 0.05),
      during which females also exhibited greater VC than males (P < 0.05). CONCLUSION:
      Our findings suggest that the normalized MBABF and VC in females, who experience
      less muscle fatigue, are greater during intermittent maximal voluntary handgrip
      exercise.

PMID- 18317377
TI  - ACE genotype and the muscle hypertrophic and strength responses to strength
      training.
AB  - PURPOSE: Previous studies have linked an insertion/deletion polymorphism in the
      angiotensin-converting enzyme (ACE) gene with variability in muscle strength
      responses to strength training (ST), though conclusions have been inconsistent
      across investigations. Moreover, most previous studies have not investigated the
      influence of sex on the association of ACE I/D genotype with muscle phenotypes.
      The purpose of this study was to investigate the association of ACE genotype with
      muscle phenotypes before and after ST in older men and women. METHODS: Eighty-six
      inactive men and 139 inactive women, ages 50-85 yr (mean: 62 yr), were studied
      before and after 10 wk of unilateral knee extensor ST. The one-repetition maximum
      (1RM) test was used to assess knee extensor muscle strength, and computed
      tomography was used to measure quadriceps muscle volume (MV). Differences were
      compared among ACE genotype groups (II vs ID vs DD). RESULTS: Across the entire
      cohort at baseline, ACE genotype was significantly associated with total lean
      mass and body weight, with higher values in DD genotype carriers (both P < 0.05).
      At baseline, DD genotype carriers exhibited significantly greater MV compared
      with II genotype carriers for both the trained leg (men: 1828 +/- 44 vs 1629 +/-
      70; women: 1299 +/- 34 vs 1233 +/- 49; P = 0.02) and untrained leg (men: 1801 +/-
      46 vs 1559 +/- 72; women: 1268 +/- 36 vs 1189 +/- 51; P = 0.01), with no
      significant genotype x sex interaction. No ACE genotype associations were
      observed for the 1RM or MV adaptations to ST in either men or women. CONCLUSIONS:
      In the present study, ACE genotype was associated with baseline differences in
      muscle volume, but it was not associated with the muscle hypertrophic response to
      ST.

PMID- 18317378
TI  - Do sex or race differences influence strength training effects on muscle or fat?
AB  - PURPOSE: To examine the influence of sex and race on the effects of strength
      training (ST) on thigh muscle volume (MV), midthigh subcutaneous fat (SCF), and
      intermuscular fat (IMF). METHODS: One hundred eighty-one previously inactive
      healthy Caucasian (N = 117) and African American (N = 54) men (N = 82) and women
      (N = 99), aged 50-85 yr, underwent about 10 wk of unilateral knee extension ST.
      Ten subjects were neither Caucasian nor African American and were, therefore, not
      included in the race analysis. Quadriceps MV and midthigh SCF and IMF cross
      sectional area were measured with computed tomography before and after ST. Sex
      and race comparisons were made with a 2 x 2 (sex by race) analysis of covariance.
      RESULTS: Training-induced increases in absolute MV were significantly greater (P
      < 0.001) in men than in women, though both sex groups increased MV significantly
      with ST (P < 0.001), and the relative (%) increases were similar. There were
      significant increases in MV within race groups (P < 0.001), but no significant
      differences between races. There were no significant changes in SCF or IMF,
      whether sex and racial groups were separated or combined. In addition, there was
      no sex by race interaction for changes in MV, SCF, or IMF with ST. CONCLUSION:
      Strength training does not alter subcutaneous or intermuscular fat, regardless of
      sex or racial differences. Although men exhibit a greater muscle hypertrophic
      response to strength training than do women, the difference is small. Race does
      not influence this response.

PMID- 18317379
TI  - Sex differences in pulmonary function during exercise.
AB  - Structural and hormonal sex differences are known to exist that may influence the
      pulmonary system's response to exercise. Specifically, women tend to show reduced
      lung size, decreased maximal expiratory flow rates, reduced airway diameter, and
      a smaller diffusion surface than age- and height-matched men. Additionally,
      ovarian hormones, namely progesterone and estrogen, are known to modify and
      influence the pulmonary system. These differences may have an effect on airway
      responsiveness, ventilation, respiratory muscle work, and pulmonary gas exchange
      during exercise. Recent evidence suggests that during exercise, women demonstrate
      greater airway hyperresponsiveness and expiratory flow limitation, increased work
      of breathing, and, perhaps, greater exercise-induced arterial hypoxemia compared
      with men. The consequence of these pulmonary effects may influence exercise
      capacity.

PMID- 18317380
TI  - Response of the myocardium to exercise: sex-specific regulation of hsp70.
AB  - Sex is a potent modifier of the cardiovascular system because males and females
      differ in several aspects of the heart's biology and physiology.
      Epidemiologically, premenopausal women possess a distinct advantage over men in
      the occurrence of cardiovascular heart disease; however, this advantage shifts to
      men once a negative cardiac event has occurred. The reasons for these differences
      are not completely understood and are likely attributable to many factors.
      Nonetheless, the sex hormones seem to be important regulators of myocardial
      health. Of particular note, the sex hormones influence the molecular and
      physiological responses of the heart to the stress of exercise including the
      expression of several vital proteins such as the cardioprotective 70-kDa heat
      shock protein, Hsp70. This review will focus on the exercise-induced expression
      of Hsp70 and how it is modified by sex. A better understanding of how sex, the
      sex hormones in particular, modifies the exercise stress response has important
      implications in the prescription of exercise to males and females, young or old.

PMID- 18317381
TI  - Sex differences in exercise metabolism and the role of 17-beta estradiol.
AB  - Women oxidize more lipid and less carbohydrate and protein compared with men
      during endurance exercise. The increase in fat oxidation is associated with
      higher intramyocellular lipid content and use as well as greater adipocyte
      lipolysis. Glucose rates of appearance and disappearance are lower for women than
      for men, with no change in basal muscle glycogen, and some evidence for muscle
      glycogen sparing during endurance exercise. Women oxidize less protein compared
      with men and show lower leucine oxidation during exercise. The consistent and
      robust finding of higher mRNA abundance for most components of fat-oxidation
      pathways in women compared with men is directionally consistent with the
      substrate-oxidation data. A lack of directional consistency between mRNA species
      involved in carbohydrate and protein metabolism and the known sex differences
      during exercise implies that fat oxidation is regulated and that carbohydrate and
      protein oxidation follow by metabolic demand. Administration of 17-beta-estradiol
      to men recapitulates most of the described sex differences in metabolism and mRNA
      content. The greater fat oxidation for women during submaximal endurance exercise
      compared with men seems to occur partly through a sex hormone-mediated
      enhancement of lipid-oxidation pathways.

PMID- 18317382
TI  - Exercise physiologists talk about sex differences.
AB  - The number of publications addressing sex differences and exercise physiology has
      increased from 12, before 1970, to as many as 1344 through October 2007,
      according to a recent PubMed search. The following symposium represents three
      distinct examples of how exercise physiologists are approaching the issue of sex
      differences in various aspects of physiology. Tarnapolsky presents data from
      studies of sex and sex hormone effects on substrate use, a factor that may
      distinguish between the capacities of women and men to excel at exercise
      performance at different durations and intensities. Harms and Rosenkranz provide
      insight into the potential limitations of respiratory function at increased
      exercise intensities in the female sex attributable, in part, to sex-based
      anatomic differences in respiratory anatomy. Milne and Noble discuss important
      findings concerning the cardioprotective aspect of exercise-induced heat shock
      proteins versus the inherent cardioprotection of elevated estradiol
      concentrations in young women. Each paper demonstrates the novel methodology and
      sophisticated research designs currently being employed to discern sex
      differences and sex hormone effects on various aspects of exercise physiology.

PMID- 18317383
TI  - Television time and continuous metabolic risk in physically active adults.
AB  - PURPOSE: Among Australian adults who met the public health guideline for the
      minimum health-enhancing levels of physical activity, we examined the dose
      response associations of television-viewing time with continuous metabolic risk
      variables. METHODS: Data were analyzed on 2031 men and 2033 women aged > or = 25
      yr from the 1999-2000 Australian Diabetes, Obesity and Lifestyle study without
      clinically diagnosed diabetes or heart disease, who reported at least 2.5 h.wk of
      moderate- to vigorous-intensity physical activity. Waist circumference, resting
      blood pressure, and fasting and 2-h plasma glucose, triglycerides, and high
      density-lipoprotein cholesterol (HDL-C) were measured. The cross-sectional
      associations of these metabolic variables with quartiles and hours per day of
      self-reported television-viewing time were examined separately for men and for
      women. Analyses were adjusted for age, education, income, smoking, diet quality,
      alcohol intake, parental history of diabetes, and total physical activity time,
      as well as menopausal status and current use of postmenopausal hormones for
      women. RESULTS: Significant, detrimental dose-response associations of television
      viewing time were observed with waist circumference, systolic blood pressure, and
      2-h plasma glucose in men and women, and with fasting plasma glucose,
      triglycerides, and HDL-C in women. The associations were stronger in women than
      in men, with significant gender interactions observed for triglycerides and HDL
      C. Though waist circumference attenuated the associations, they remained
      statistically significant for 2-h plasma glucose in men and women, and for
      triglycerides and HDL-C in women. CONCLUSIONS: In a population of healthy
      Australian adults who met the public health guideline for physical activity,
      television-viewing time was positively associated with a number of metabolic risk
      variables. These findings support the case for a concurrent sedentary behavior
      and health guideline for adults, which is in addition to the public health
      guideline on physical activity.

PMID- 18317384
TI  - Patterns of objectively measured physical activity in the United States.
AB  - PURPOSE: We used latent class analysis (LCA) to assess patterns of physical
      activity among adults, using the 7 d of accelerometer data from the 2003-2004
      NHANES. METHODS: For each participant, we determined the daily minutes of
      moderate-to-vigorous physical activity (MVPA), vigorous physical activity (VPA),
      and minutes of MVPA that occurred in bouts of 10 min. Participants were then
      categorized into patterns of activity, using LCA and adjusting for
      sociodemographic characteristics. RESULTS: For overall MVPA, five classes of
      physical activity were defined, including two least active classes, which
      averaged less than 25 min of MVPA per day and represented 78.7% of the total
      study population. The most active class averaged 134 min of MVPA per day and
      comprised 0.9% of the population. The results for bout minutes of MVPA were
      similar to the patterns produced for overall MVPA, with the exception of a
      "weekend warrior" class with moderate levels of physical activity Monday through
      Friday but with a much higher level of activity on the weekend, particularly on
      Sunday. This class represented 1.8% of the population. Only 1.4% of all days
      achieved 10 min or more of VPA, and in 91.1% of all days, participants
      accumulated less than 1 min of VPA. The LCA analysis of VPA did not produce
      stable results, because of the small number of participants registering any
      minutes of VPA. CONCLUSION: Our results indicate that a very large portion of the
      U.S. population may be classified into patterns of physical activity that
      represent low levels of MVPA throughout the week. The LCA analysis provided a
      novel approach for assessing patterns of objectively measured physical activity
      in epidemiologic studies.

PMID- 18317385
TI  - Physical activity levels among children attending after-school programs.
AB  - PURPOSE: To describe the physical activity (PA) levels of children attending
      after-school programs, 2) examine PA levels in specific after-school sessions and
      activity contexts, and 3) evaluate after-school PA differences in groups defined
      by sex and weight status. METHODS: One hundred forty-seven students in grades 3-6
      (mean age: 10.1 +/- 0.7, 54.4% male, 16.5 % overweight (OW), 22.8% at-risk for
      OW) from seven after-school programs in the midwestern United States wore
      Actigraph GT1M accelerometers for the duration of their attendance to the
      program. PA was objectively assessed on six occasions during an academic year
      (three fall and three spring). Stored activity counts were uploaded to a
      customized data-reduction program to determine minutes of sedentary (SED), light
      (LPA), moderate (MPA), vigorous (VPA), and moderate-to-vigorous (MVPA) physical
      activity. Time spent in each intensity category was calculated for the duration
      of program attendance, as well as specific after-school sessions (e.g., free
      play, snack time). RESULTS: On average, participants exhibited 42.6 min of SED,
      40.8 min of LPA, 13.4 min of MPA, and 5.3 min of VPA. The average accumulation of
      MVPA was 20.3 min. Boys exhibited higher levels of MPA, VPA, and MVPA, and lower
      levels of SED and LPA, than girls. OW and at-risk-for-OW students exhibited
      significantly less VPA than nonoverweight students, but similar levels of LPA,
      MPA, and MVPA. MVPA levels were significantly higher during free-play activity
      sessions than during organized or structured activity sessions. CONCLUSION: After
      school programs seem to be an important contributor to the PA of attending
      children. Nevertheless, ample room for improvement exists by making better use of
      existing time devoted to physical activity.

PMID- 18317386
TI  - Exercise reduces inflammation and cell proliferation in rat colon carcinogenesis.
AB  - PURPOSES: There is evidence that the risk of colon cancer is reduced by
      appropriate levels of physical exercise. Nevertheless, the mechanisms involved in
      this protective effect of exercise remain largely unknown. Inflammation is
      emerging as a unifying link between a range of environment exposures and
      neoplastic risk. The carcinogen dimethyl-hydrazine (DMH) induces an increase in
      epithelial cell proliferation and in the expression of the inflammation-related
      enzyme cyclooxigenase-2 (COX-2) in the colon of rats. Our aim was to verify
      whether these events could be attenuated by exercise. METHODS: Four groups of
      eight Wistar rats were used in the experiment. The groups G1 and G3 were
      sedentary (controls), and the groups G2 and G4 were submitted to 8 wk of swimming
      training, 5 d.wk. The groups G3 and G4 were given subcutaneous injections of DMH
      immediately after the exercise protocols. Fifteen days after the neoplasic
      induction, the rats were sacrificed and the colon was processed for histological
      examination and immunohistochemistry staining of proliferating cell nuclear
      antigen (PCNA) and COX-2. RESULTS: We found a significant increase in the PCNA
      labeling index in both DMH-treated groups of rats. However, this increase was
      significantly attenuated in the training group G4 (P < 0.01). Similar results
      were observed in relation to the COX-2 expression. CONCLUSIONS: From our
      findings, we conclude that exercise training exerts remarkable antiproliferative
      and antiinflammatory effects in the rat colonic mucosa, suggesting that this may
      be an important mechanism to explain how exercise protects against colonic
      cancer.

PMID- 18317387
TI  - Reduced leg blood flow during submaximal exercise in type 2 diabetes.
AB  - It is unclear whether impaired cardiac and/or vascular function contribute to
      exercise intolerance in patients with type 2 diabetes. PURPOSE: Magnetic
      resonance imaging (MRI) was used to determine whether reductions in cardiac
      output and/or femoral arterial blood flow contribute to reduced aerobic capacity
      in patients with type 2 diabetes. METHODS: Cardiac and femoral arterial blood
      flow MRI scans were performed at rest and during low-intensity leg exercise in
      eight patients with type 2 diabetes and 11 healthy individuals. Maximal aerobic
      capacity VO(2 max) and maximal oxygen pulse were also determined in all
      participants. RESULTS: V O(2 max) was 20% lower and maximal oxygen pulse was 16%
      lower in patients with type 2 diabetes (P < 0.05), whereas maximal heart rate was
      the same between groups. Low-intensity exercise induced a 20% increase in heart
      rate and cardiac output as well as a 60-70% increase in femoral blood flow in
      both groups (P < 0.05). Femoral arterial blood flow indexed to thigh lean mass
      was reduced during exercise in patients with type 2 diabetes compared with
      healthy individuals. Stroke volume indexed to fat-free mass was lower in patients
      with type 2 diabetes, but greater heart rate allowed cardiac output to be
      maintained during submaximal exercise. CONCLUSIONS: These findings suggest that
      impaired femoral arterial blood flow, an indirect marker of muscle perfusion,
      affects low-intensity exercise performance in patients with type 2 diabetes.
      However, because of lower exercising stroke volume, we propose that femoral
      arterial blood flow and, possibly, cardiac output, limit V O(2 max) in patients
      with type 2 diabetes.

PMID- 18317388
TI  - Incidence and risk factors of acute traumatic primary patellar dislocation.
AB  - PURPOSE: The purpose of this study was to investigate incidence, nature, and risk
      factors of primary traumatic patellar dislocations. METHODS: We identified acute
      first-time traumatic patellar dislocations from a national hospital discharge
      register. Patients with previous patellar dislocations, subluxations, or knee
      traumas were excluded. The sample consisted of 128,714 Finnish male conscripts
      (median age 20). Background risk factor data were obtained from a Finnish
      conscript service database. The dislocators were observed during their service
      period for a short-term outcome. RESULTS: From the 128,714 male conscripts, 278
      had patellar dislocations, and 72 were classified as having sustained first-time
      traumatic patellar dislocations. The 128,436 nondislocators served as a control
      group. The incidence of acute traumatic primary patellar dislocations among male
      conscripts was 77.4 (95% CI: 61.1-96.8) per 100,000 persons per year. The male
      patients with traumatic primary patellar dislocations were taller (P = 0.03) and
      weighed more (P = 0.02) than the controls. Hemarthrosis was present in all
      patients, and when MRI or open surgery was performed, medial retinacular
      disruption and medial patellofemoral ligament (MPFL) injury were identified.
      Patients' return to military service was unrelated to the choice of treatment.
      CONCLUSION: Primary patellar dislocation is not a negligible cause of morbidity
      among young male adults. It can be concluded that hemarthrosis and MPFL rupture
      are the definite signs of an acute traumatic primary patellar dislocation. Height
      and weight were significant risk factors, whereas poor physical performance was
      not associated with primary patellar dislocation.

PMID- 18317389
TI  - Determinants of heart rate recovery following exercise in children.
AB  - PURPOSE: Heart rate (HR) recovery during the first minute after cessation of
      exercise is predominantly modulated by reactivation of vagal tone. Attenuated 1
      min HR recovery is a cardiovascular risk factor in adults. The purpose of this
      study was to determine predictors of 1-min HR recovery after a maximum-effort
      exercise test in healthy children. METHODS: HR recovery after cessation of a
      maximal treadmill exercise test (Bruce protocol) was assessed in 485 children
      (197 girls, 288 boys) who underwent an exercise test during their clinical
      evaluation to exclude cardiac disease and who were discharged as normal. The
      first-minute cool-down period (1.5 mph, 0% inclination on treadmill) was
      consistent for all subjects. Age- and gender-specific 25th, 50th, and 75th
      percentile values of 1-min HR recovery were generated. Multivariable linear
      regression analyses were performed to determine predictors of 1-min HR recovery.
      RESULTS: One-minute HR recovery was higher in boys and correlated inversely with
      age and with age-adjusted BMI in both boys and girls. In a multivariable linear
      regression model, age, gender, BMI, and baseline HR were significant predictors
      of 1-min HR recovery and explained 39% of variance. Exercise duration and peak HR
      were also significant predictors when added to the model, but they improved the
      explained variance by only 2%. CONCLUSION: One-minute HR recovery after exercise
      is attenuated with age in children. Children with higher BMI, particularly those
      who are overweight, and those with lower exercise endurance, have slower 1-min HR
      recovery.

PMID- 18317390
TI  - Tape that increases medial longitudinal arch height also reduces leg muscle
      activity: a preliminary study.
AB  - PURPOSE: : To evaluate the initial effects of antipronation taping (APT) on foot
      posture and electromyographic (EMG) activity of tibialis anterior (TA), tibialis
      posterior (TP), and peroneus longus (PL) muscles during walking. METHODS: : Five
      asymptomatic individuals who exhibited lower medial longitudinal arch height on a
      clinical assessment of gait walked on a treadmill for 10 min before and after the
      application of an APT technique-specifically, the augmented low-Dye. Arch height
      (AH) in standing as well as peak and average amplitude, duration, time of onset,
      and time of offset of recorded EMG activity during walking were analyzed for each
      condition. RESULTS: : APT produced a mean (95% confidence interval (CI)) increase
      in AH of 12.9% (6.5-19.3; P = 0.005). Mean (95% CI) reductions in peak and
      average EMG activation of TA (peak: -23.9% (-34.0 to -13.9); average: -7.8% (
      13.6 to -2.0)) and TP (peak: -45.5% (-77.3 to -13.7); average: -21.1% (-41.6 to 
      0.6)) were observed when walking with APT (P < 0.05). The APT also produced a
      small increase in duration of TA EMG activity of 3.7% (0.9-6.5) of the stride
      cycle duration, largely because of an earlier onset of EMG activity (4.4%; -8.1
      to -0.8 of a stride cycle; P < 0.05). CONCLUSION: : APT reduces activity of the
      TA and TP muscles during walking while increasing AH, which provides preliminary
      evidence of its role in reducing the load of these key extrinsic muscles of the
      ankle and the foot. Follow-up study is required to evaluate these findings.

PMID- 18317391
TI  - Phylogeny of the stapes prosthesis.
AB  - OBJECTIVE: To create the first ever stapes prosthesis phylogenetic tree for the
      evolution of the stapes prosthesis. STUDY DESIGN: Retrospective literature
      review, personal interviews. SETTING: University Medical Center. PATIENT: Not
      applicable. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Construction of
      a stapes prosthesis phylogenetic tree with branches capable of including all
      stapes prostheses. RESULTS: One hundred five different stapes prostheses were
      reviewed, starting with the first-ever prosthesis used in the first stapedectomy
      and continuing up to the present time. The stapes prosthesis family tree contains
      4 main branches that allow for categorization of all the commercial prostheses
      currently used. Many examples of atavistic prostheses, single surgeon use, and
      dead-end characteristics exist. CONCLUSION: An overview of the complicated
      phylogenetic tree for stapes prostheses gives great perspective to the history of
      stapedectomy and insights into many characteristics that are useful for designing
      new stapes prostheses.

PMID- 18317392
TI  - Prednisone treatment for vestibular neuritis.
AB  - OBJECTIVE: To evaluate the value of corticosteroids in the treatment of
      vestibular neuritis (VN). DESIGN: Prospective controlled randomized. METHODS:
      Thirty VN patients, 15 in the study and 15 in the control group, were the
      subjects of the study. The study group was treated by 1 mg/kg prednisone for 5
      days, followed by gradually reduced doses of prednisone for an additional 15
      days, and vestibular sedatives for symptomatic relief during the first 5 days
      after presentation. The control group received a placebo and similar vestibular
      sedatives. The patients had a baseline evaluation and follow-up examinations
      after 1, 3, 6, and 12 months. The groups were compared for the presence of
      symptoms and signs, caloric lateralization on the electronystagmography (ENG),
      the presence of other pathologic findings in the ENG, and Dizziness Handicap
      Inventory scores. RESULTS: No differences were found between the groups in the
      occurrence of symptoms and signs, degree of caloric lateralization, presence of
      other ENG pathologic findings, and Dizziness Handicap Inventory scores at the end
      of the study. Complete resolution was observed in 64% of the study and in 80% of
      the control group. The study group showed earlier recovery of ENG lateralization
      at the 1- and 3-month follow-up evaluations and higher rates of complete
      resolution at the 3- and 6-month follow-up points. CONCLUSION: Prednisone therapy
      might enhance earlier recovery but does not improve the long-term prognosis of
      VN. The clinical and laboratory parameters in VN are not correlated, and both are
      required for complete patient evaluation.

PMID- 18317393
TI  - Outcomes for conservative management of traumatic conductive hearing loss.
AB  - OBJECTIVES: To evaluate the natural history of traumatic conductive hearing loss.
      STUDY DESIGN: Retrospective chart review. METHODS: Otologic and audiometric
      evaluations of patients in the early posttraumatic phase were compared with
      evaluations at follow-up. Assessment included etiologies of trauma,
      classification of hearing loss, factors causing conductive loss, and analyses of
      changes in air-bone gaps, pure-tone averages and hearing loss class. RESULTS:
      There were 45 patients, representing 47 ears, with sufficient initial and follow
      up documentation to analyze the natural history of traumatic conductive hearing
      loss. Overall, 77% of ears showed an improvement in pure-tone averages without
      surgical intervention. Air-bone gaps closed from an average of 24.8 +/- 12.1 to
      13.2 +/- 11.1 dB. Only 11% of ears demonstrated a decrease in pure-tone averages,
      and 12% showed no change in thresholds. All forms of injury contributing to the
      conductive hearing loss had good outcomes. Specifically, tympanic membrane
      perforations showed final air-bone gaps of 14.9 +/- 11.2 dB; cases of
      hemotympanum had final air-bone gaps of 10.0 +/- 8.1 dB; and suspected ossicular
      chain disruptions had final air-bone gaps of 13.9 +/- 12.3 dB. Only 5 of 47 ears
      ultimately required surgical intervention for persistent pathology. CONCLUSION:
      Patients with all forms of traumatic conductive hearing loss can be initially
      managed conservatively. Even suspected ossicular chain disruptions have a high
      rate of spontaneous reparation. Surgical intervention for perforation or
      conductive hearing loss should be undertaken in the rare cases when these
      conditions persist greater than 6 months.

PMID- 18317394
TI  - Adenoid cystic carcinoma of the parotid gland with temporal bone invasion.
AB  - OBJECTIVE: To present our series of 16 patients with adenoid cystic carcinoma
      (ACC) of the parotid gland with temporal bone invasion. PATIENTS: All patients
      treated at our institution between July 1988 and July 2004 with parotid gland ACC
      with temporal bone invasion. INTERVENTIONS: Preoperative radiographic assessment
      with combined surgical and radiation therapy treatment. MAIN OUTCOME MEASURES:
      Postoperative- or radiation-related complications and overall 2-, 5-, and 10-year
      survival. RESULTS: The most common surgically related complications were new
      onset cranial nerve deficits, whereas osteoradionecrosis of the bony external
      auditory canal was the most frequently noted complication associated with
      radiation therapy. The overall survival rates at 2, 5, and 10 years were 94, 75,
      and 60%, respectively. CONCLUSION: Lateral cranial base access should be used in
      the extirpation of ACC of the parotid gland with temporal bone involvement.

PMID- 18317395
TI  - Evaluation of the short hybrid electrode in human temporal bones.
AB  - HYPOTHESIS: The current hybrid electrode can be inserted without trauma to the
      temporal bone and, after insertion, assumes a position within the scala tympani
      near the outer cochlear wall just beneath the basilar membrane. BACKGROUND:
      Conservation of residual hearing after cochlear implant electrode insertion
      requires a special insertion technique and an atraumatic short electrode. This
      allows electroacoustic stimulation in ears with significant residual hearing.
      METHODS: Human cadaveric temporal bones were implanted with soft surgical
      technique under fluoroscopic observation. Dehydrated and resin-impregnated bones
      are dissected. Real-time electrode insertion behavior and electrode position were
      evaluated. The bones are examined for evidence of insertion-related trauma.
      RESULTS: No gross trauma was observed in the implanted bones, and the electrode
      dynamics evaluation revealed smooth scala tympani insertions. CONCLUSION:
      Atraumatic insertion of the 10-mm hybrid electrode can be accomplished using an
      appropriate cochleostomy and insertion technique.

PMID- 18317396
TI  - Predicting outcome of malignant external otitis.
AB  - OBJECTIVE: Malignant external otitis (MEO) continues to pose a diagnostic and
      therapeutic challenge. The lack of a diagnostic study since 1987 combined with
      recent findings of quinolone-resistant MEO prompted the present analysis of MEO
      outcome in a major tertiary medical center. METHODS: Seventy-five consecutive
      patients hospitalized for suspected MEO between 1990 and 2003 were divided into 2
      diagnostic groups: MEO Type 1, presence of all obligatory clinical and radiologic
      criteria and most of the occasional criteria of Cohen and Friedman or absence of
      1 obligatory criterion with failure of intensive treatment, and MEO Type 2,
      absence of one of the obligatory criteria with treatment response within 1 week.
      The groups were compared for demographic data, underlying diseases, ear
      parameters, culture findings, length of hospitalization, and treatment before
      hospitalization, obtained from the charts. RESULTS: Both types of MEO affected
      mostly diabetic patients and were characterized by granulations and discharge in
      the external ear, severe prolonged pain, soft tissue involvement and bone
      destruction on computed tomographic scan, and growth of Pseudomonas aeruginosa in
      culture. However, Type 1 MEO was associated with a significantly older patient
      age at presentation, higher rate of oral antidiabetic treatment, history of
      diabetic (vascular) complications, computed tomographic findings of
      nasopharyngeal involvement (soft tissue swelling, soft tissue asymmetry, or
      abscess formation), bone destruction, and temporomandibular joint involvement-all
      of which led to significantly longer treatment and shorter survival. CONCLUSION:
      The worse prognosis of Type 1 MEO compared with Type 2 should alert clinicians to
      establish earlier diagnosis and treatment.

PMID- 18317397
TI  - Otologics fully implantable hearing system: Phase I trial 1-year results.
AB  - OBJECTIVE: To assess the safety of the Otologics fully implantable hearing system
      after 1 year of use in a Phase I clinical trial. STUDY DESIGN: Repeated-measures
      within-subjects design. SETTING: Procedures were performed in a variety of
      facilities, including a university, military, and private hospital's ambulatory
      surgical center and outpatient clinical audiologic test facilities. PATIENTS:
      Adult patients with bilateral moderate to severe sensorineural hearing loss.
      INTERVENTION(S): Surgical insertion of this prosthesis included an atticotomy to
      expose the incus, securing the transducer to the mastoid bone, attaching the
      transducer tip to the incus via insertion into a laser-drilled hole, and
      postauricular implantation of the microphone/battery/electronics capsule. MAIN
      OUTCOME MEASURE(S): Subjective patient benefit, aided sound field thresholds, and
      speech discrimination with the subject's own, appropriately fit, walk-in hearing
      aid(s) and the prosthesis were assessed. RESULTS: There were no pre-post-implant
      differences noted for bone conduction: slight differences were noted in the pre
      post-implant air conduction results (p < 0.05). These differences were attributed
      to the healing process and reversed to almost preimplant assessment levels by the
      third-month evaluation. Pure-tone averages and monaural word recognition scores
      were slightly better for the walk-in-aided condition (p < 0.05), whereas the
      patient benefit scales favored the postoperative implant-aided conditions.Adverse
      effects of the implant were encountered on 14 occasions after the implantation of
      the 20 subjects. With the exception of partial device extrusions (that occurred
      later), all were rectified by the time of initial activation. At the 12-month
      data collection point, problems that had been encountered by subjects included 1)
      partial device extrusion (3 subjects), necessitating explantation in 2; 2) loss
      of external communication (2 subjects), resulting in 1 explantation; and 3)
      increased charging times beyond 1.5 hours (7), resulting in 3 explantations and 2
      patients not using their device while awaiting explantation. CONCLUSION: Phase I
      trial results provide evidence that this fully implantable device can provide
      sound amplification to sensorineural hearing loss patients, with performance
      results similar to the patients' walk-in hearing aids.

PMID- 18317398
TI  - Diode laser in otosclerosis surgery: first clinical results.
AB  - OBJECTIVE: To evaluate the functional results of otosclerosis surgery using diode
      laser. STUDY DESIGN: Retrospective cohort analysis. PATIENTS: One hundred seven
      patients operated on for otosclerosis with a diode laser (119 ears, all primary
      cases) and 141 patients operated on with a conventional technique (141 ears, all
      primary cases). Revision cases using the diode laser were also described.
      METHODS: Preoperative tomographic computed scan findings and intraoperative
      observations were collected. Pure-tone and vocal audiometry was performed
      preoperatively and postoperatively (at 3 mo and 1 yr). RESULTS: In the laser
      group, the air-bone gap was 29 +/- 0.8 dB (n= 112) preoperatively and 9 +/- 0.6
      dB (n = 58) at 1 year. Air conduction was improved by 22 +/- 1.7 dB at 1 year (n
      = 58). In the conventional group, the air-bone gap was 32 +/- 0.9 dB (n=127)
      preoperatively and 10 +/- 0.6 dB (n = 127) at 1 year. Air conduction was improved
      by 25 +/- 1.1 dB (n = 127) at 1 year. No difference of hearing gain was observed
      between the 2 groups at 1 year. A decreased rate of footplate fracture was
      observed with the diode laser (3.6%) compared with the conventional technique
      (21.3%). CONCLUSION: Diode laser is a reliable and safe device for otosclerosis
      surgery. The functional results were similar to those reported in other series.

PMID- 18317399
TI  - Predicting cochlear implant outcomes in children with auditory neuropathy.
AB  - OBJECTIVE: To examine the outcome of cochlear implantation in children with
      auditory neuropathy (AN) and cochlear nerve deficiency (Group A). Results are
      compared with a cohort of children with AN and normal cochlear nerves (Group B).
      STUDY DESIGN: Retrospective cohort study. SETTING: The Sydney Cochlear Implant
      Centre and the Children's Hospital at Westmead. PATIENTS: Children younger than
      15 years with bilateral profound sensorineural hearing loss and the diagnosis of
      AN confirmed on electrophysiologic testing. All children underwent cochlear
      implantation with Nucleus 24 cochlear implants from 1997 to 2006. INTERVENTIONS:
      Magnetic resonance imaging was examined for deficiency of the vestibulocochlear
      nerve. Brain and inner ear abnormalities were recorded. Cochlear implant outcomes
      and demographic variables were compared. MAIN OUTCOME MEASURES: Melbourne speech
      perception score (MSPS) at 1 year and implant evoked electric auditory brainstem
      response (EABR). RESULTS: Group A performed significantly worse on both
      parameters than Group B. In Group A, median MSPS was 1, compared with a median
      score of 4 in Group B (z = -3.010; p = 0.003). EABR was abnormal in 13 of 15
      (87%) children in Group A, compared with 9 of 39 (23%) in Group B. Children in
      both groups with abnormal EABR had significantly worse MSPS (z = -2.780; p =
      0.005). Fourteen of 15 children with cochlear nerve deficiency had associated
      inner ear abnormalities. CONCLUSION: Children with AN can have associated
      cochlear nerve deficiency. These patients have worse speech perception scores at
      1 year post cochlear implantation, higher rates of abnormal EABR, and more
      associated inner ear abnormalities than children with AN and normal cochlear
      nerves.

PMID- 18317400
TI  - Posttranslational activation of endothelial nitric oxide synthase attenuates
      carbon tetrachloride-induced hepatotoxicity in newborn rats.
AB  - Nitric Oxide (NO) can be cytotoxic or cytoprotective depending on amount and
      location of its generation. eNOS is important in modulating blood flow and is
      allosterically regulated. Inducible NOS (iNOS) tends to produce large quantities
      of NO leading to cell injury. We studied the role and regulation of NOS in carbon
      tetrachloride (CCl(4))-induced hepatotoxicity in newborn rats. eNOS was expressed
      before birth, significantly increased on day of life (DOL) 2 reaching a maximum
      at DOL-20. iNOS was absent at all ages. CCl(4) treatment resulted in hepatic
      injury in newborn rats and damage was intensified by co-administration of a
      general NOS inhibitor. CCl(4) treatment increased eNOS activity without change in
      mRNA or protein levels. Administration of CCl(4) resulted in an increase in
      phosphorylation of threonine protein kinase (Akt) and eNOS, associated with an
      increase in eNOS activity. Administration of wortmannin (phosphatidylinositol 3
      kinase, PI3 K, inhibitor) attenuated the phosphorylation of Akt and eNOS and
      reduced eNOS activity. Co-administration of CCl(4) and wortmannin potentiated the
      degree of hepatic injury. iNOS was not detectable in CCl(4)-treated rats. This
      data indicates a protective role for eNOS in CCl(4)-induced hepatotoxicity in
      newborn rats with protection accomplished by activation of eNOS via
      posttranslational modification of the PI3 K/Akt signaling pathway.

PMID- 18317401
TI  - Augmented and accelerated nephrogenesis in TGF-beta2 heterozygous mutant mice.
AB  - Several members of the transforming growth factor-beta (TGF-beta) superfamily
      play key roles in kidney development, either directly or indirectly regulating
      nephron number. Although low nephron number is a risk factor for cardiovascular
      and renal disease, the implications of increased nephron number has not been
      examined due to the absence of appropriate animal models. Here, using unbiased
      stereology we demonstrated that kidneys from TGF-beta2 heterozygous (TGF-beta2(+/
      )) mice have approximately 60% more nephrons than wild-type mice at postnatal day
      30. To determine whether augmented nephron number involved accelerated ureteric
      branching morphogenesis, embryonic day 11.5 metanephroi were analyzed via
      confocal microscopy. A 40% increase in total ureteric branch length was observed
      in TGF-beta2(+/-) kidneys, together with an extra generation of branching. In
      embryonic day 12.5 metanephroi cultured for 48 h the numbers of both ureteric
      tree tips and glomeruli were significantly greater in TGF-beta2(+/-) kidneys.
      These findings suggest that augmented nephron number in TGF-beta2(+/-) kidneys
      results from accelerated ureteric branching morphogenesis and nephron formation.
      Manipulation of TGF-beta2 signaling in vivo may provide avenues for protection or
      rescue of nephron endowment in fetuses at risk.

PMID- 18317402
TI  - Long-term functional and protective actions of preconditioning with hypoxia,
      cobalt chloride, and desferrioxamine against hypoxic-ischemic injury in neonatal
      rats.
AB  - Preconditioning with hypoxia and hypoxia-mimetic compounds cobalt chloride
      (CoCl2) and desferrioxamine (DFX) protects against hypoxic-ischemic (HI) injury
      in neonatal rat brain. We examined long-term functional and protective actions of
      preconditioning induced by hypoxia, CoCl(2) and DFX in a neonatal rat model of
      HI. Postnatal day six rat pups were exposed to preconditioning with hypoxia (8%
      oxygen) or injections of CoCl(2), DFX or saline vehicle and 24 h later rats
      underwent HI or sham surgery. Behavioral tests were performed and at the
      conclusion of experiments, brains removed for morphologic analyses. HI resulted
      in a large unilateral lesion in the ipsilateral hemisphere compared with sham
      control rats. All preconditioning treatments significantly reduced the total
      lesion volume. Behavioral deficits were observed in HI rats compared with sham
      controls. The reduction in forelimb grasping strength in HI rats was attenuated
      by preconditioning with hypoxia, CoCl(2) and DFX. HI increased the number of foot
      faults in a grid-walking test and resulted in forelimb asymmetry in the cylinder
      test. Only preconditioning with hypoxia reversed all three functional deficits
      after HI. These findings indicate that preconditioning, especially when induced
      by hypoxia, has the potential to minimize the morphologic and functional effects
      of neonatal HI injury.

PMID- 18317403
TI  - The effect of superoxide dismutase overexpression on hepatic gluconeogenesis and
      whole-body glucose oxidation during resuscitated normotensive murine septic
      shock.
AB  - Besides excess cytokine and NO production, enhanced oxygen radical formation was
      referred to contribute to the impaired hepatic gluconeogenesis during sepsis or
      endotoxemia. Therefore, we tested the hypothesis that genetic overexpression of
      the Cu/Zn-superoxide dismutase (SOD-1) may restore the sepsis-related lack of the
      norepinephrine-induced increase in hepatic gluconeogenesis and whole-body glucose
      oxidation. Anesthetized, ventilated, and instrumented wild-type control, and
      heterozygous and homozygous SOD-1-overexpressing mice received hydroxyethyl
      starch and norepinephrine to maintain normotensive hemodynamics measured at 18,
      21, and 24 h after cecal ligation and puncture (CLP) or sham operation. Hepatic
      gluconeogenesis and whole-body glucose oxidation were calculated from liver
      tissue isotope and expiratory 13CO2 enrichments during continuous i.v.
      1,2,3,4,5,6-13C6-glucose. Superior mesenteric artery and portal vein flows
      (ultrasound flow probes) and hepatic microcirculatory perfusion (Laser Doppler
      flowmetry) and O2 saturation (remission spectrophotometry) were comparable in the
      CLP and sham-operated animals, without any difference related to the mouse
      strain. Despite continuous i.v. norepinephrine necessary in the CLP mice, both
      glycemia and hepatic gluconeogenesis were similar, irrespective of the presence
      of sepsis and the genetic strain. Glucose oxidation rate progressively increased
      in the CLP groups, again without difference between the genetic strains. The
      surgery- and CLP-induced increase in liver cell oxidative DNA damage (tail moment
      in the comet assay) was less pronounced in the homozygous mice. Heterozygous nor
      homozygous SOD-1 overexpression did not improve the sepsis-related impairment of
      carbohydrate metabolism, possibly because of the lacking increase of the tissue
      catalase and the mitochondrial SOD activity, and the ongoing i.v. norepinephrine.

PMID- 18317404
TI  - Neutrophil-derived circulating free DNA (cf-DNA/NETs): a potential prognostic
      marker for posttraumatic development of inflammatory second hit and sepsis.
AB  - The release of "neutrophil extracellular traps" (NETs) has been identified as a
      novel immune response in innate immunity. Neutrophil extracellular traps are
      composed of neutrophil-derived circulating free DNA (cf-DNA), histones, and
      neutrophil cytoplasm-derived proteins such as proteases. Here, we studied the
      putative predictive value of plasma cf-DNA/NETs for the development of sepsis and
      mortality after multiple trauma. In a prospective pilot study with 45 multiple
      trauma (Injury Severity Score>16) patients, cf-DNA was directly quantified in
      plasma. Blood samples were sequentially obtained daily from admission to our
      Trauma Center until day 10. Because of limited intensive care unit (ICU) stay of
      less than 3 days, 8 patients have been excluded, resulting in 37 patients that
      were evaluated. Time kinetics of cf-DNA/NETs was compared with C-reactive protein
      (CRP), interleukin (IL) 6, leukocyte counts, and myeloperoxidase. The severity of
      the injury was calculated on the basis of the Injury Severity Score, as well as
      Multiple Organ Dysfunction Score, Sequential Organ Failure Assessment, and
      Simplified Acute Physiology Score II on ICU. Initially high cf-DNA/NETs values
      (>800 ng/mL) with recurrent increased values between days 5 to 9 were associated
      with subsequent sepsis, multiple organ failure, and death. In conjunction with cf
      DNA/NETs, IL-6 was significantly elevated after admission. However, the
      development of a second hit was not indicated by IL-6. In contrast to cf
      DNA/NETs, no difference in CRP kinetics was observed between patients with and
      without development of sepsis. Circulating free DNA/NETs kinetics rather followed
      kinetics of Multiple Organ Dysfunction Score, Sepsis-related Organ Failure
      Assessment, leukocyte counts, and partially of myeloperoxidase. Circulating free
      DNA/NETs seems to be a valuable additional marker for the calculation of injury
      severity and/or prediction of inflammatory second hit on ICU. However, a large
      clinical trial with severely injured patients should confirm the prognostic value
      of neutrophil-derived cf-DNA/NETs.

PMID- 18317405
TI  - Pulmonary contusion induces alveolar type 2 epithelial cell apoptosis: role of
      alveolar macrophages and neutrophils.
AB  - Alveolar type 2 (AT-2) cell apoptosis is an important mechanism during lung
      inflammation, lung injury, and regeneration. Blunt chest trauma has been shown to
      activate inflammatory cells such as alveolar macrophages (AMs) or neutrophils
      (polymorphonuclear granulocytes [PMNs]), resulting in an inflammatory response.
      The present study was performed to determine the capacity of different
      components/cells of the alveolar compartment (AMs, PMNs, or bronchoalveolar
      lavage [BAL] fluids) to induce apoptosis in AT-2 cells following blunt chest
      trauma. To study this, male Sprague-Dawley rats were subjected to either sham
      procedure or blunt chest trauma induced by a single blast wave. Various time
      points after injury (6 h to 7 d), the lungs were analyzed by
      immunohistochemistry, for AT-2 cells, or with antibodies directed against caspase
      3, caspase 8, Fas, Fas ligand (FasL), BAX, and BCL-2. Bronchoalveolar lavage
      concentrations of TNF-alpha, IL-1beta, and soluble FasL were determined by enzyme
      linked immunosorbent assay. Furthermore, cultures of AT-2 cells isolated from
      healthy rats were incubated with supernatants of AMs, PMNs, or BAL fluids
      obtained from either trauma or sham-operated animals in the presence or absence
      of oxidative stress. Annexin V staining or TUNEL (terminal deoxynucleotidyl
      transferase) assay was used to detect apoptotic AT-2 cells. Histological
      evaluation revealed that the total number of AT-2 cells was significantly reduced
      at 48 h following trauma. Fas, FasL, active caspase 8, and active caspase 3 were
      markedly up-regulated in AT-2 cells after chest trauma. BAX and BCL-2 did not
      show any significant changes between sham and trauma. IL-1beta, but not TNF
      alpha, levels were markedly increased at 24 h after the injury, and soluble FasL
      concentrations were significantly enhanced at 6, 12, 24, and 48 h after the
      insult. Apoptosis of AT-2 cells incubated with supernatants from cultured AMs,
      isolated at 48 h following chest trauma was markedly increased when compared with
      shams. In contrast, no apoptosis was induced in AT-2 cells incubated with
      supernatants of activated PMNs or BAL fluids of traumatized animals. In summary,
      blunt chest trauma induced apoptosis in AT-2 cells, possibly involving the
      extrinsic death receptor pathway. Furthermore, mediators released by AMs appeared
      to be involved in the induction of AT-2 cell apoptosis.

PMID- 18317406
TI  - Endogenous retroviruses in systemic response to stress signals.
AB  - Infection of germline cells with retroviruses initiates permanent proviral
      colonization of the germline genome. The germline-integrated proviruses, called
      endogenous retroviruses (ERVs), are inherited to offspring in a Mendelian order
      and belong to the transposable element family. Endogenous retroviruses and other
      long terminal repeat retroelements constitute ~8% and ~10% of the human and mouse
      genomes, respectively. It is likely that each individual has a distinct genomic
      ERV profile. Recent studies have revealed that a substantial fraction of ERVs
      retains the coding potentials necessary for virion assembly and replication.
      There are several layers of potential mechanisms controlling ERV expression:
      intracellular transcription environment (e.g., transcription factor pool,
      splicing machinery, hormones), epigenetic status of the genome (e.g., proviral
      methylation, histone acetylation), profile of transcription regulatory elements
      on each ERV's promoter, and a range of stress signals (e.g., injury, infection,
      environment). Endogenous retroviruses may exert pathophysiologic effects by
      infection followed by random reintegration into the genome, by their gene
      products (e.g., envelope, superantigen), and by altering the expression of
      neighboring genes. Several studies have provided evidence that ERVs are
      associated with a range of pathogenic processes involving multiple sclerosis,
      systemic lupus erythematosus, breast cancer, and the response to burn injury. For
      instance, the proinflammatory properties of the human ERV-W envelope protein play
      a central role in demyelination of oligodendrocytes. As reviewed in this article,
      recent advances in ERV biology and mammalian genomics suggest that ERVs may have
      a profound influence on various pathogenic processes including the response to
      injury and infection. Understanding the roles of ERVs in the pathogenesis of
      injury and infection will broaden insights into the underlying mechanisms of
      systemic immune disorder and organ failure in these patients.

PMID- 18317407
TI  - TLR ligand decreases mesenteric ischemia and reperfusion injury-induced gut
      damage through TNF-alpha signaling.
AB  - Ischemic gut contributes to the development of sepsis and organ failure in
      critically ill patients. Toll-like receptors (TLRs) have been reported to mediate
      the pathophysiology of organ damage following ischemia/reperfusion (I/R) injury.
      We hypothesize that LPS, a ligand for TLR4, decreases mesenteric I/R injury
      induced gut damage through tumor necrosis factor alpha (TNF-alpha) signaling.
      First, wild-type (WT) mice were fed with oral antibiotics for 4 weeks to deplete
      the intestinal commensal microflora. At week 3, drinking water was supplemented
      with LPS (10 microg/microL) to trigger TLRs. The intestinal mucosa was harvested
      for TLR4 protein, caspase 3 activity, and terminal deoxynucleotide transferase
      labeling assay. Second, WT and Tnfrsf1a mice received 30-min ischemia and 30-min
      reperfusion (30I-30R) or 30I-180R of the intestine; intestinal permeability and
      lipid peroxidation of the intestine were examined. Third, WT and Tnfrsf1a mice
      were fed with oral antibiotics with or without LPS and received 30I-180R of the
      intestine. The intestinal mucosa was harvested for lipid peroxidation;
      glutathione (GSH) level; nuclear factor kappaB (NF-kappaB) and AP-1 DNA-binding
      activity; Bcl-w, TNF-alpha, and CXCR2 mRNA expression; and HSP70 protein assay.
      Commensal depletion increased caspase 3 activity as well as villi apoptosis and
      decreased TLR4 expression of the intestinal mucosa. LPS increased TLR4 expression
      and decreased villi apoptosis. Commensal depletion augmented 30I-180R-induced
      intestine permeability as well as lipid peroxidation and decreased GSH level in
      WT mice but not in Tnfrsf1a mice. LPS decreased 30I-180R-induced intestinal
      permeability as well as lipid peroxidation and increased GSH level of the
      intestinal mucosa in WT mice but not in Tnfrsf1a mice. Commensal depletion with
      30I-180R increased NF-kappaB and AP-1 DNA-binding activity, HSP70 protein
      expression, and decreased Bcl-w and TNF-alpha mRNA expression of the intestinal
      mucosa in WT mice but not in Tnfrsf1a mice. Collectively, commensal microflora
      induces TLR4 expression and decreases apoptosis of the intestinal mucosa.
      Commensal depletion enhances I/R-induced gut damage. LPS prevents I/R-induced
      intestinal permeability, lipid peroxidation, and decrease in GSH level. Given
      that the preventive effect of LPS on I/R-induced gut damage and NF-kappaB
      activity of the intestine is abolished in Tnfrsf1a mice, we conclude that TLR
      ligand decreases mesenteric I/R injury-induced gut damage through TNF-alpha
      signaling.

PMID- 18317408
TI  - regulatory effects of hypoxia-inducible factor 1alpha on vascular reactivity and
      its mechanisms following hemorrhagic shock in rats.
AB  - The purpose of the present study is to investigate the regulatory effect of
      hypoxia-inducible factor 1alpha (HIF-1alpha) on vascular reactivity and its
      mechanism after hemorrhagic shock (HS). Gene expression of HIF-1alpha and its
      downstream molecules, including eNOS, iNOS, cyclooxygenase 2 (COX-2), and heme
      oxygenase 1 (HO-1), and plasma nitric monoxide (NO), prostaglandin (PGI), and
      whole blood carbon monoxide (CO) were determined after HS in rats with or without
      oligomycin, the specific antagonist of HIF-1alpha. The vascular reactivity was
      determined via observing the constriction initiated by norepinephrine in isolated
      organ perfusion system. The results indicated that HIF-1alpha, eNOS, iNOS, HO-1,
      and COX-2 messenger RNA expression exhibited a time-dependent increase after HS,
      although the expression of these genes and their products, NO, CO, and PGI were
      suppressed by oligomycin to some extent. The vascular reactivity revealed a
      biphasic change, which was increased compensatorily at the early stage of HS
      (immediate to 1 h after shock) and decreased progressively at the decompensatory
      period after 4 h of shock. Oligomycin treatment partly inhibited the vascular
      reactivity at early stage (immediate to 1 h after shock) and improved it at
      decompensatory period at 4 to 6 h after shock (P < 0.01). The results suggested
      that HIF-1alpha plays an important regulatory role in the change of vascular
      reactivity after HS in rats. The possible mechanism of HIF-1alpha regulating
      vascular reactivity is closely related to its regulation on the expression of
      eNOS, iNOS, HO-1, COX-2 and the production of NO, CO and PGI.

PMID- 18317409
TI  - Persistent inhibition of mitochondrial permeability transition by preconditioning
      during the first hours of reperfusion.
AB  - Mitochondrial permeability transition pore (mPTP) opening is a crucial event in
      cardiomyocyte death after I/R. We questioned whether preconditioning (PC) may
      inhibit mPTP opening during ischemia and/or during reperfusion and whether this
      effect would persist as reperfusion evolves. Anesthetized New Zealand white
      rabbits underwent a test ischemia followed by reperfusion. Ischemia lasted either
      10 or 30 min, whereas reperfusion duration varied from 5 to 20, 60 and up to 240
      min. For each duration of ischemia and reperfusion, animals were randomized as
      either control or PC. Preconditioning was induced by 5 min of ischemia followed
      by 5 min of reperfusion. Mitochondria were isolated from myocardium at risk for
      assessment of the calcium retention capacity (CRC) (potentiometric technique)
      used here as an index of sensitivity of the mPTP to Ca2+ loading. In controls,
      the CRC was moderately reduced after ischemia alone, but reperfusion severely and
      time-dependently accelerated further CRC reduction. Preconditioning failed to
      modify mPTP opening during ischemia alone, but significantly improved CRC during
      reperfusion. This protective effect persisted as reperfusion evolved. These data
      suggest that (a) reperfusion strikingly increases the susceptibility to Ca2+
      induced mPTP opening, and that (b) PC inhibits mPTP opening at reflow and
      throughout the first hours of reperfusion.

PMID- 18317410
TI  - Inhibition of p53 by pifithrin-alpha reduces myocyte apoptosis and leukocyte
      transmigration in aged rat hearts following 24 hours of reperfusion.
AB  - Ischemic heart disease is a common age-related disease. Apoptotic cell death and
      inflammation are the major contributors to I/R injury. The mechanisms that
      trigger myocyte apoptosis and inflammation during myocardial I/R (MI/R) remain to
      be elucidated. Published data from our laboratory demonstrated that pretreatment
      of MI/R rats with pifithrin-alpha (PFT), a specific p53 inhibitor, reduced
      myocyte apoptosis and improved cardiac function compared with MI/R rats
      pretreated with saline at 4 h of reperfusion. In the present study, we
      investigated the effects of PFT on the occurrence of myocyte apoptosis and
      leukocyte transmigration in the later period of reperfusion. Aged (20-month-old)
      male F344 rats were subjected to 30 min of myocardial ischemia via ligature of
      the LCA, followed by 24 h of reperfusion. Pifithrin-alpha (2.2 mg/kg,
      intraperitoneally) or saline was administered to rats before ischemia. The
      results indicate that pretreatment of MI/R rats with PFT significantly decreased
      the percentage of infarct area to ischemic area (33 +/- 8 vs. 54 +/- 9, P < 0.05)
      and improved cardiac output (79 +/- 11 vs. 38 +/- 9 mL/min per 100 g body weight,
      P < 0.05) when compared with rats pretreated with saline at 24 h of reperfusion.
      The protective effects of PFT may involve the p53/Bax-mediated apoptosis because
      treatment of MI/R rats with PFT attenuated the ratio of Bax to Bcl2 (0.97 +/- 0.1
      vs. 2.1 +/- 0.2, P < 0.05) and reduced myocyte apoptosis. Interestingly,
      inhibition of p53 transcriptional function by PFT alleviated leukocyte
      infiltration into the ischemic area of the heart (339 +/- 37 vs. 498 +/- 75
      cells/10 high-power fields, P < 0.05). These data suggest that inhibition of p53
      transcriptional function by PFT attenuates myocyte apoptosis and alleviates
      leukocyte transmigration at 24 h of reperfusion. The mechanisms by which p53
      modulates leukocyte transmigration require further investigation.

PMID- 18317411
TI  - Dynamical system analysis of Staphylococcus epidermidis bloodstream infection.
AB  - Unlike many localized infections, the development and resolution of bacteremia
      involves physical and immunological interactions between many anatomic sites. In
      an effort to better understand these interactions, we developed a computational
      model of bacteremia as a dynamical system fashioned after multicompartmental
      pharmacodynamic models, incorporating bacterial proliferation and clearance in
      the blood, liver, spleen, and lungs, and the transport of pathogens between these
      sites. A system of four first-order homogeneous ODEs was developed. Blood and
      organ bacterial burdens were measured at various time points from 3 to 48 h
      postinoculation using an LD25 murine model of Staphylococcus epidermidis
      bacteremia. Using these empiric data, solutions to the mathematical model were
      recovered. A bootstrap resampling method was used to generate 95% confidence
      intervals around the solved parameters. The validity of the model was examined in
      parallel experiments using animals acutely immunocompromised with
      cyclophosphamide; the model captured abnormalities in bacterial partitioning
      previously described with this antineoplastic agent. Lastly, the approach was
      used to explore possible benefits to clinically observed hyperdynamic blood flow
      during sepsis: in simulation, normal mice, but not those treated with
      cyclophosphamide, enjoyed significantly more rapid bacterial clearance from the
      bloodstream under hyperdynamic conditions.

PMID- 18317412
TI  - Mitochondrial ischemia-reperfusion injury of the transplanted rat heart: improved
      protection by preservation versus cardioplegic solutions.
AB  - Cold ischemia time and preservation of organs are limited by I/R injury leading
      to primary nonfunction of the graft. In a rat heart transplant model, we compared
      cardioplegic St Thomas (ST) to histidine-tryptophan-ketoglutarate (HTK) and
      University of Wisconsin preservation solutions in terms of contractile function,
      and mitochondrial respiratory and enzymatic defects after prolonged cold ischemia
      and reperfusion. Contractile function was scored after transplantation and 24 h
      of reperfusion. Mitochondrial function was investigated by high-resolution
      respirometry of permeabilized myocardial fibers. Graft performance in terms of
      contractile function declined with the duration of cold storage. Recovery was
      significantly improved after 10 h of cold storage in HTK compared with ST
      (cardiac scores, 3.3+/-0.5 and 1.8+/-0.8, respectively). Tissue lactate
      dehydrogenase was better preserved in HTK than ST. Increase of tissue water
      content (edema) was less pronounced in HTK than ST (3.33+/-0.14 and 3.73+/-0.21
      mg/mg dry weight, respectively). Similar cardiac scores (2.6+/-0.9 and 2.9+/-1.2,
      respectively) and mitochondrial respiratory parameters were obtained after
      preservation in HTK and University of Wisconsin. Decline in contractile function
      of individual grafts correlated well with loss of mitochondrial respiratory
      capacity, whereas citrate synthase activity remained largely preserved,
      indicating specific damage of respiratory complexes. Our data provide evidence
      for the superiority of preservation solutions versus a cardioplegic solution for
      prolonged cold storage of the heart. The correlation of graft performance and
      mitochondrial function indicates the potential of high-resolution respirometry
      for quantitative assessment of myocardial injury upon cold I/R, providing a basis
      for diagnostic approaches and evaluation of improved preservation solutions for
      heart transplantation.

PMID- 18317422
TI  - The CTSAs, the Congress, and the scientific method.

PMID- 18317423
TI  - JIM interview with dr. Judith L. Swain.

PMID- 18317424
TI  - The effect of a disease management algorithm and dedicated postacute coronary
      syndrome clinic on achievement of guideline compliance: results from the parkland
      acute coronary event treatment study.
AB  - BACKGROUND: The application of disease management algorithms by physician
      extenders has been shown to improve therapeutic adherence in selected
      populations. It is unknown whether this strategy would improve adherence to
      secondary prevention goals after acute coronary syndromes (ACSs) in a largely
      indigent county hospital setting. METHODS: Patients admitted for ACS were
      randomized at the time of discharge to usual follow-up care versus the same care
      with the addition of a physician extender visit. Physician extender visits were
      conducted according to a treatment algorithm based on contemporary practice
      guidelines. Groups were compared using the primary end point of achievement of
      low-density lipoprotein treatment goals at 3 months after discharge and
      achievement of additional evidence-based practice goals. RESULTS: One hundred
      forty consecutive patients were randomized. A similar proportion of patients
      returned for study follow-up in both groups at 3 months (54 [79%]/68 in the usual
      care group vs 57 [79%]/72 in the intervention group; P = 0.97). Among those
      completing the 3-month visit, a low-density lipoprotein cholesterol level less
      than 100 mg/dL was achieved in 37 (69%) of the usual care patients compared with
      35 (57%) of those in the intervention group (P = 0.43). There was no statistical
      difference in implementation of therapeutic lifestyle changes (smoking cessation,
      cardiac rehabilitation, or exercise) between groups. Prescription rates of
      evidence-based therapeutics at 3 months were similar in both groups. CONCLUSION:
      The implementation of a post-ACS clinic run by a physician extender applying a
      disease management algorithm did not measurably improve adherence to evidence
      based secondary prevention treatment goals. Despite initially high rates of
      evidence-based treatment at discharge, adherence with follow-up appointments and
      sustained implementation of evidence-based therapies remains a significant
      challenge in this high-risk cohort.

PMID- 18317425
TI  - Serum ghrelin concentrations are increased in children with growth hormone
      insensitivity and decrease during long-term insulinlike growth factor-I
      treatment.
AB  - BACKGROUND: Ghrelin increases food intake, body weight, and growth hormone (GH)
      secretion. Serum concentrations of ghrelin are low in obese hyperinsulinemic
      persons, are reduced by infusion of insulin into normal-weight subjects, and are
      increased in underweight hypoinsulinemic patients with anorexia nervosa. Laron
      syndrome is an autosomal recessive disorder of GH insensitivity that results in
      decreased insulinlike growth factor-I (IGF-I) synthesis and growth failure. These
      patients have elevated GH levels, excess adipose tissue, and are insulin
      resistant. Because IGF-I has insulinlike actions and patients with GH
      insensitivity syndrome (GHIS) exhibit excess adiposity, we sought to determine
      whether ghrelin levels were elevated in these patients and potentially regulated
      by IGF-I replacement. METHODS: Thirteen children with GHIS and 20 normal control
      children matched for age, sex, and body mass index underwent complete physical
      examination and a fasting blood draw at baseline. The GHIS subjects then
      underwent follow-up fasting blood draws during therapy with human recombinant IGF
      I (80-120 mug/kg, given subcutaneously twice daily). Fasting glucose, insulin,
      and IGF-I concentrations were measured at the time of collection. Fasting total
      ghrelin levels were measured on stored serum samples. RESULTS: The GHIS subjects
      had 2-fold higher fasting ghrelin levels (2926 +/- 1869 pg/mL) compared with the
      normal control children (1492 +/- 493 pg/mL; P = 0.009), and mean ghrelin values
      were reduced 56% during 6.4 +/- 0.2 years of IGF-I replacement (P < 0.05).
      CONCLUSIONS: Growth hormone resistance and low IGF-I levels are associated with
      elevated ghrelin levels, which may potentiate GH secretion and adiposity in these
      children. Suppression of ghrelin during IGF-I treatment suggests a novel
      mechanism potentially regulating ghrelin levels.

PMID- 18317426
TI  - Prediction of cerebrovascular and cardiovascular events in patients with
      subclinical carotid atherosclerosis: the role of C-reactive protein.
AB  - BACKGROUND: Several studies have suggested that inflammation and infection may be
      important for accelerated progression of atherosclerosis, but few data are
      available on subjects with early stages of atherosclerosis. METHODS AND RESULTS:
      We included, in a prospective 5-year follow-up study, 150 patients with
      subclinical carotid atherosclerosis, evaluating at baseline all established
      traditional cardiovascular risk factors (eg, older age, male sex, obesity,
      hypertension, diabetes, smoking, family history of coronary artery disease, and
      dyslipidemia); 2 markers of inflammation, fibrinogen, and high-sensitivity C
      reactive protein (CRP); and the seropositivity to Helicobacter pylori, Chlamydia
      pneumoniae, and cytomegalovirus. After follow-up, cardiovascular and
      cerebrovascular events were registered in the 19% of patients, and the increment
      in CRP levels (in quintiles) was significantly associated with ischemic stroke (P
      = 0.0253), acute myocardial infarction (P = 0.0055), cardiovascular or
      cerebrovascular death (P = 0.0145), and the presence of any event (P = 0.0064).
      Most traditional cardiovascular risk factors (eg, older age, hypertension,
      diabetes, and dyslipidemia) were significantly associated with the events but
      only in the unadjusted analysis; in fact, at logistic regression analysis, among
      all baseline variables, only elevated CRP levels showed a predictive role (odds
      ratio, 7.0; 95% confidence interval, 2.2-18.4; P = 0.0247). CONCLUSIONS: Our
      findings suggest that elevated CRP concentrations may significantly influence the
      occurrence of cerebrovascular and cardiovascular events in patients with baseline
      subclinical carotid atherosclerosis. Notably, null findings were obtained by
      viral and bacteria titers, suggesting a greater role of inflammation (and not of
      infection) in the progression of atherosclerosis in our cohort. However, further
      studies are needed to evaluate the therapeutic implications in this category of
      patients.

PMID- 18317433
TI  - PPARgamma: a novel molecular target in lung disease.
AB  - Interest in peroxisome proliferator-activated receptors (PPARs) has steadily
      increased over the past 15 years. The recognition that subclasses of this
      receptor played critical roles in regulation of metabolism led to the development
      of synthetic ligands and their widespread application in the treatment of type 2
      diabetes. At the same time, emerging evidence demonstrated that the influence of
      PPARs extends well beyond metabolism and diabetes. A salient example of this can
      be seen in studies that explore the role of PPARs in lung cell biology. In fact,
      current literature suggests that PPAR receptors may well represent exciting new
      targets for treatment in a variety of lung disorders. In an attempt to keep the
      scientific and medical communities abreast of these developments, a symposium
      sponsored by the American Federation for Medical Research entitled "PPARgamma: A
      Novel Molecular Target in Lung Disease" was convened on April 29, 2007, at the
      Experimental Biology Meeting in Washington, DC. During that symposium, 4 speakers
      reviewed the latest developments in basic and translational research as they
      relate to specific lung diseases. Jesse Roman, MD, professor and director of the
      Emory University Division of Pulmonary, Allergy, and Critical Care Medicine,
      reviewed the role of PPARgamma in the pathogenesis of lung cancer and its
      implications for therapy. Raju Reddy, MD, assistant professor of Medicine at the
      University of Michigan, presented data regarding the immunomodulatory role of
      PPARgamma in alveolar macrophages. Patricia J. Sime, MD, associate professor of
      Medicine, Environmental Medicine, and Oncology at the University of Rochester
      School of Medicine, discussed the antifibrogenic potential of PPARgamma ligands
      in pulmonary fibrosis. Finally, C. Michael Hart, MD, professor of Medicine at
      Emory University and chief of the Atlanta Veterans Affairs Medical Center
      Pulmonary Section, reviewed the role of PPARgamma in pulmonary vascular disease.
      This brief introduction to the symposium will provide background information
      about PPARs to facilitate the general reader's appreciation of the more in-depth
      and disease-specific discussions that follow.

PMID- 18317434
TI  - The Role of PPARgamma in pulmonary vascular disease.
AB  - The peroxisome proliferator-activated receptor (PPAR) gamma is a member of the
      nuclear hormone receptor superfamily of ligand-activated transcription factors.
      Thiazolidinediones, pharmacological ligands for PPARgamma, are currently used in
      the management of type 2 diabetes. Peroxisome proliferator-activated receptor
      gamma is expressed in the lung and pulmonary vasculature, and its expression is
      reduced in the vascular lesions of patients with pulmonary hypertension.
      Furthermore, thiazolidinedione PPARgamma ligands reduced pulmonary hypertension
      and vascular remodeling in several experimental models of pulmonary hypertension.
      This report reviews current evidence that PPARgamma may represent a novel
      therapeutic target in pulmonary hypertension and examines studies that have begun
      to elucidate mechanisms that underlie these potential therapeutic effects.

PMID- 18317435
TI  - Immunomodulatory role of PPAR-gamma in alveolar macrophages.
AB  - The lung is constantly exposed to inhaled pathogens and toxins yet totally
      dependent on the integrity of a delicate alveolar-capillary interface for its
      function. Much of the balance between protection and collateral damage rests on
      the alveolar macrophage, which not only phagocytoses inhaled particles but also
      modulates the activity of both innate and acquired immune systems to limit
      unnecessary or exuberant inflammation. In its resting state, the alveolar
      macrophage secretes anti-inflammatory mediators while limiting antigen
      presentation to the adaptive immune system. The alveolar macrophage's state of
      activation is regulated by a variety of factors, including the activity of the
      nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma).
      Peroxisome proliferator-activated receptor gamma agonists reduce the ability of
      inflammatory stimuli to activate the alveolar macrophage while simultaneously
      stimulating phagocytosis of both opsonized and unopsonized particles, via the
      Fcgamma and CD36 receptors, respectively. All known endogenous PPAR-gamma ligands
      are fatty acid derivatives, and macrophage-specific knockout of the enzyme that
      converts esterified fatty acids to free fatty acids results in severe lung
      inflammation. Peroxisome proliferator-activated receptor gamma expression is
      reduced in alveolar macrophages from patients with pulmonary sarcoidosis and
      alveolar proteinosis, suggesting that the deficiency may play a role in
      pathogenesis of these diseases. In summary, these observations point to PPAR
      gamma in the context of the alveolar macrophage as a crucial factor in limiting
      excessive and possibly injurious inflammation in the lung.

PMID- 18317436
TI  - Peroxisome proliferator-activated receptor gamma and lung cancer biology:
      implications for therapy.
AB  - Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear
      receptor family of transcriptional modulators. In addition to their known roles
      in regulation of metabolism and inflammation, PPARs have also been implicated in
      carcinogenesis based on studies showing their ability to modulate cellular
      differentiation, proliferation, and apoptosis. Of the 3 PPARs identified to date
      (PPARalpha, PPARbeta/delta, and PPARgamma), PPARgamma has been studied the most
      in part because of the availability of PPARgamma agonists (also known as
      PPARgamma ligands). In many tumor cells, including lung carcinoma cells,
      activation of PPARgamma results in decreased cellular proliferation; this is
      particularly true for non-small cell lung carcinoma, the most common malignant
      lung tumor in the United States. Studies performed in xenograft models of lung
      cancer also show decreased tumor growth and progression in animals treated with
      PPARgamma ligands. More recently, data are emerging from retrospective clinical
      studies that suggest a protective role for PPARgamma ligands on the incidence of
      lung cancer. This review summarizes the available data that implicate PPARs in
      lung carcinogenesis while focusing on PPARgamma as a potential target for the
      development of novel anti-lung cancer treatment strategies.

PMID- 18317437
TI  - The antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis.
AB  - Pulmonary fibrosis is characterized by the accumulation of fibroblasts,
      myofibroblasts, collagen, and other extracellular matrix proteins in the
      interstitium of the lung, with subsequent scarring and destruction of the
      alveolar capillary interface. In some cases, pulmonary fibrosis is preceded by
      lung inflammation and can be treated with anti-inflammatory therapies. However,
      idiopathic pulmonary fibrosis is characterized by a relative paucity of
      underlying inflammation and currently has no effective treatment. There is
      increasing evidence that the transcription factor peroxisome proliferator
      activated receptor (PPAR) gamma plays an important role in controlling cell
      differentiation and that PPARgamma ligands can modify inflammatory and fibrotic
      responses. Peroxisome proliferator-activated receptor gamma ligands, including
      the thiazolidinedione class of antidiabetic drugs and novel triterpenoid
      compounds derived from oleanic acid, inhibit TGF-beta-stimulated profibrotic
      differentiation of lung fibroblasts in vitro and reduce lung scarring in animal
      models of fibrosis. The mechanism of action of the PPARgamma ligands is under
      investigation but seems to involve both PPARgamma-dependent and PPARgamma
      independent pathways. These in vitro and in vivo data highlight the potentially
      exciting role of PPARgamma ligands as novel therapies for fibrosis of the lung
      and other organ systems prone to scarring. Many of the synthetic PPARgamma
      ligands are orally active, and several are currently available and Food Drug
      Administration approved for use in therapy of type 2 diabetes. Further research
      is urgently required to more clearly elucidate the mechanism of action of these
      drugs and to develop more potent antifibrotic agents for patients with scarring
      diseases for whom there are currently few effective therapies.

PMID- 18317438
TI  - Improvement in insulin sensitivity and dyslipidemia in protease inhibitor-treated
      adult male patients after switch to atazanavir/ritonavir.
AB  - BACKGROUND: Treatment of human immunodeficiency virus (HIV) with protease
      inhibitors (PIs) is associated with insulin resistance, triglyceride-rich
      dyslipidemia, and fat redistribution. Atazanavir (ATV), a potent once-daily PI,
      has been recognized for its convenience to patients, and some studies describe
      improved lipid metabolism. However, its effects on insulin sensitivity have not
      been elucidated. We conducted this study to test the hypothesis that ATV improves
      insulin resistance and dyslipidemia. METHODS: We prospectively studied 9 HIV
      infected men with dyslipidemia (median age, 53 years; baseline triglyceride
      level, >200 mg/dL) on stable PI-containing antiretroviral therapy who elected to
      change PI therapy to ritonavir-boosted ATV therapy, dose of 300/100 mg. We
      measured insulin resistance at baseline and after 12 weeks of therapy using a
      hyperinsulinemic euglycemic clamp (insulin dose, 200 mU/m minute). Fasting lipid
      profiles and body composition (whole-body dual energy x-ray absorptiometry) were
      also measured at baseline and after 12 weeks. RESULTS: All 9 patients completed
      the study and maintained undetectable viral loads (<50 copies/mL) and stable CD4
      counts. After 12 weeks, insulin sensitivity significantly improved (+28%; P =
      0.008) in all patients. Triglyceride levels also improved. CONCLUSIONS: Using the
      gold-standard euglycemic clamp, ritonavir-boosted ATV therapy improved PI-induced
      insulin resistance among dyslipidemic HIV-infected men on PI-based antiretroviral
      therapy. These findings were not attributable to a change in body weight and
      provide further evidence for ATV's unique metabolic profile among the PIs.

PMID- 18317439
TI  - Are uremia, diabetes, and atherosclerosis linked with impaired antioxidant
      mechanisms?
AB  - BACKGROUND: Oxidative stress is a new risk factor for atherosclerosis. Increased
      oxidative stress in hemodialysis (HD) patients may arise from uremia-associated
      metabolic/humoral abnormalities and bioincompatibility of dialysis. Patients with
      diabetes mellitus (DM) may be subject to an additional risk. Respective
      influences of uremia, diabetes, and HD duration in accelerated atherosclerosis
      and oxidative stress have not been clarified yet. METHODS: The study was
      performed on 24 nondiabetic HD patients, 23 diabetic HD patients, 20 stages 3 to
      4 chronic kidney disease patients, and 21 diabetic patients without overt
      nephropathy. Carotid intima-media thickness, a surrogate of atherosclerosis, was
      measured by high-resolution B-mode ultrasonography. Oxidant status was determined
      by lipid peroxidation as expressed by malondialdehyde (MDA); antioxidant status
      was determined by superoxide dismutase, catalase, glutathione peroxidase, reduced
      intracellular glutathione, and plasma thiol. RESULTS: Intima-media thickness
      (IMT) was higher in patients undergoing HD but not different between nondiabetic
      HD patients and diabetic HD patients. No correlation was found between the
      duration of HD and intima-media thickness. Antioxidants were generally lower in
      HD patients. Intima-media thickness was positively correlated with MDA and
      negatively correlated with plasma thiol. Among other risk factors, only age was
      correlated with intima-media thickness. CONCLUSIONS: Increased carotid IMT in HD
      patients is independent of duration of HD or diabetes status. Age and MDA are the
      significant predictors of carotid IMT. Increased oxidative stress due to impaired
      antioxidant mechanisms, particularly reduced plasma thiol redox potential, may
      account for accelerated atherosclerosis in high-risk patients with chronic kidney
      failure and/or DM.

PMID- 18317441
TI  - Issues and trends in pediatric growth hormone therapy--an update from the
      GHMonitor observational registry.
AB  - The GHMonitor observational registry collates data on pediatric subjects
      receiving Saizen (recombinant human growth hormone (GH)) therapy. From January
      2003 through August 2006, 1335 subjects were enrolled in the registry,
      approximately two-thirds of whom are male. The most common diagnosis in the
      registry is idiopathic growth hormone deficiency (58%). Most subjects in
      GHMonitor are receiving Saizen doses using a needle-free delivery device, the
      cool.click (73%). Mean height standard deviation scores show an improvement from 
      2.1 at screening to -1.1 following 3 years of Saizen therapy. To date, adverse
      events have been reported in 4% of subjects. Three serious adverse events were
      identified to be related to Saizen by the primary investigator: cellulitis at the
      injection site, behavioral problems/suicidal ideation, and enlargement of a
      craniopharyngioma. This article provides an update on data from the registry and
      briefly discusses topical and controversial issues in the treatment of pediatric
      patients requiring GH therapy.

PMID- 18317442
TI  - Neuroimaging for the pediatric endocrinologist.
AB  - Imaging of the sella and surrounding structures has become essential in the
      evaluation of pituitary dysfunction and its causes. This article begins with a
      review of the normal anatomy of the sella and the imaging patterns in and about
      the normal pituitary gland. There exists considerable variability in the size and
      configuration of the normal gland in all age groups, and absolute determination
      of a 'large' or 'small' gland can prove difficult and problematic. Absence of the
      posterior bright-spot may indicate disruption of the normal stalk transport
      mechanisms. Microadenomas are well-resolved by magnetic resonance imaging as
      areas with reduced or delayed enhancement relative to the normal gland. Among
      hormonally active tumors, adrenocorticotropic hormone-releasing adenomas are most
      common in the first 11 years of life, while prolactinomas become more common into
      the teenage years. Macroadenomas tend to present clinically because of mass
      effect on adjacent structures, such as the bitemporal hemianopsia seen with optic
      chiasm compression. Cystic lesions such as Rathke's cleft cysts are commonly seen
      in the gland, even in healthy children, and their presence need not correlate
      with any functional abnormality; however, such cysts can cause mass effect on the
      remaining gland, reflect hemorrhage into adenoma, or actually comprise the
      central portion of a more worrisome tumor such as craniopharyngioma. Solid tumors
      of the suprasellar region include optic pathway gliomas, hamartomas, and
      germinomas. Among inflammatory conditions, granulomatous diseases such as
      sarcoidosis have predilection for involvement of the suprasellar regions and can
      spread along perivascular spaces deep within the parenchyma. Because of the
      association of pituitary endocrinopathies with midline anomalies, one should pay
      careful attention to midline structures included on a sellar survey.

PMID- 18317443
TI  - Management of pediatric sellar tumors.
AB  - Craniopharyngiomas and pituitary adenomas are the most common forms of sellar
      tumors in children. First-line treatment usually consists of surgical resection
      of the tumor, although dopamine agonist therapy may be considered as first-line
      therapy in most patients with prolactin-secreting adenomas. Transsphenoidal
      resection has become increasingly widespread and represents the mainstay of
      surgical therapy for pituitary adenomas and selected craniopharyngiomas. Radical
      surgery, while appropriate in most patients, carries increased risks of
      postoperative morbidity, mortality and endocrinopathy. Other less invasive
      treatments include intracavitary therapy and debulking followed by radiation
      therapy or stereotactic radiosurgery. Overall, the management of these tumors
      requires a multidisciplinary approach.

PMID- 18317444
TI  - Primary and secondary disorders of lipid metabolism in pediatrics.
AB  - In the circulation, cholesterol and triglycerides are enveloped in
      apolipoproteins and phospholipids, and transported as complex particles called
      lipoproteins. Abnormal levels of lipoproteins occur in children either because of
      a genetic defect in lipid metabolism pathways (primary lipid disorders, e.g.
      familial hypercholesterolemia [FH]) or secondary to other diseases or conditions
      (e.g. insulin resistance) and can be clinically significant; for example,
      elevated low-density lipoprotein cholesterol levels are a major risk factor for
      future cardiovascular disease. Patients with primary lipid disorders in childhood
      such as FH can exhibit early atherosclerotic lesions in childhood. Other risk
      factors for cardiovascular disease, such as obesity and type 2 diabetes mellitus,
      are increasingly common in the pediatric population, and are often associated
      with dyslipidemia. Thus, pediatricians should be aware of how to screen, diagnose
      and treat dyslipidemia. The majority of lipid disorders in children can be
      managed with diet and lifestyle modification. Pharmacologic therapy (e.g.
      statins) may be added if target lipoprotein levels are not achieved. Clinicians
      may be guided in patient management by recent scientific statements from the
      American Heart Association; however, existing National Cholesterol Education
      Program treatment guidelines should be urgently updated to incorporate new
      evidence regarding atherosclerosis pathophysiology, obesity and the metabolic
      syndrome, emerging cardiovascular risk factors, and pharmacologic therapy in
      pediatric patients.

PMID- 18317445
TI  - Clinical relevance of systemic and local IGF-I: lessons from animal models.
AB  - Since the original somatomedin hypothesis was first put forward, several major
      revisions have been made. These include the identification of the insulin-like
      growth factors (IGF-I and IGF-II) and, importantly, the finding that these
      substances have local (autocrine/paracrine) as well as endocrine effects.
      Differentiating the roles of IGF-I at these different levels has been an ongoing
      challenge. However, knowledge in this area has been advanced by studies of
      knockout mice with specific gene deletions of liver IGF-I as well as IGF binding
      proteins (IGFBPs). Targeting IGFBP and the acid-labile subunit, in gene deletion
      studies, has made it possible to almost completely eliminate circulating IGF-I.
      Finally, animal models looking at IGFBPs have begun to provide insights into the
      numerous and often surprising effects these proteins themselves have. Despite the
      advances in knowledge made through these animal models, our understanding of the
      IGF-I system is still incomplete.

PMID- 18317446
TI  - Use of GnRH agonists in GH-deficient patients: arguments for and against. The
      case for GnRH agonists in GH-deficient patients.
AB  - The use of gonadotropin releasing hormone (GnRH) agonists in growth hormone (GH)
      deficient children remains controversial. Evidence suggests that GnRH agonists
      can improve adult height by delaying epiphyseal closure, thereby allowing more
      time for growth during puberty. However, long-term treatment (>3 years) with GnRH
      agonists is needed to achieve significant growth, likely related to growth rate
      deceleration with GnRH agonists. In addition, the height gained following GnRH
      agonist treatment may not be significantly greater than that achieved with GH
      treatment alone. The timely diagnosis of GH deficiency and the initiation of GH
      therapy prior to puberty may provide sufficient height gains such that GnRH
      agonist therapy may be unnecessary. A clinician must balance multiple issues when
      considering GnRH agonist therapy, including physical concerns, such as reduced
      bone mineralization, psychological concerns stemming from significantly delaying
      puberty, as well as cost:benefit analysis. This review debates the use of GnRH
      agonist therapy in GH-deficient children.

PMID- 18317447
TI  - Use of GnRH agonists in GH-deficient patients: arguments for and against. The
      case against GnRH agonists in GH-deficient patients.

PMID- 18317448
TI  - Autocrine induction of invasion and metastasis by tumor-associated trypsin
      inhibitor in human colon cancer cells.
AB  - From the conditioned medium of the human colon carcinoma cells, HT-29 5M21 (CM
      5M21), expressing a spontaneous invasive phenotype, tumor-associated trypsin
      inhibitor (TATI) was identified and characterized by proteomics, cDNA microarray
      approaches and functional analyses. Both CM-5M21 and recombinant TATI, but not
      the K18Y-TATI mutant at the protease inhibitor site, trigger collagen type I
      invasion by several human adenoma and carcinoma cells of the colon and breast,
      through phosphoinositide-3-kinase, protein kinase C and Rho-GTPases/Rho kinase
      dependent pathways. Conversely, the proinvasive action of TATI in parental HT29
      cells was alleviated by the TATI antibody PSKAN2 and the K18Y-TATI mutant. Stable
      expression of K18Y-TATI in HT-29 5M21 cells downregulated tumor growth,
      angiogenesis and the expression of several metastasis-related genes, including
      CSPG4 (13.8-fold), BMP-7 (9.7-fold), the BMP antagonist CHORDIN (5.2-fold), IGFBP
      2 and IGF2 (9.6- and 4.6-fold). Accordingly, ectopic expression of KY-TATI
      inhibited the development of lung metastases from HT-29 5M21 tumor xenografts in
      immunodeficient mice. These findings identify TATI as an autocrine transforming
      factor potentially involved in early and late events of colon cancer progression,
      including local invasion of the primary tumor and its metastatic spread.
      Targeting TATI, its molecular partners and effectors may bring novel therapeutic
      applications for high-grade human solid tumors in the digestive and urogenital
      systems.

PMID- 18317449
TI  - Eliminating epigenetic barriers induces transient hormone-regulated gene
      expression in estrogen receptor negative breast cancer cells.
AB  - In breast cancer, approximately one-third of tumors express neither the estrogen
      receptor (ERalpha) nor estrogen-regulated genes such as the progesterone receptor
      gene (PR). Our study provides new insights into the mechanism allowing hormone
      activated expression of ERalpha target genes silenced in ERalpha-negative mammary
      tumor cells. In cell lines derived from ERalpha-negative MDA-MB231 cells, stable
      expression of different levels of ERalpha from a transgene did not result in
      transcription of PR. A quantitative comparative analysis demonstrates that
      inhibiting DNA methyltransferases using 5-aza-2'-deoxycytidine or specific
      disruption of DNMT1 by small interfering RNAs and treatment with the histone
      deacetylase inhibitor trichostatin A enabled ERalpha-mediated hormone-dependent
      expression of endogenous PR. We show that demethylation of a CpG island located
      in the first exon of PR was a prerequisite for ERalpha binding to these
      regulatory sequences. Although not a general requirement, DNA demethylation is
      also necessary for derepression of a subset of ERalpha target genes involved in
      tumorigenesis. PR transcription did not subsist 4 days after removal of the DNA
      methyltransferase blocking agents, suggesting that hormone-induced expression of
      ERalpha target genes in ERalpha-negative tumor cells is transient. Our
      observations support a model where an epigenetic mark confers stable silencing by
      precluding ERalpha access to promoters.

PMID- 18317450
TI  - Mutations in the catalytic subunit of class IA PI3K confer leukemogenic potential
      to hematopoietic cells.
AB  - Constitutive activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway is
      observed in up to 70% of acute myelogenous leukemia. To investigate the relevance
      of an intrinsic PI3K-AKT pathway activation in hematopoietic malignancies, we
      analysed the effect of point mutations in the catalytic (p110alpha) and
      regulatory (p85alpha) subunit of class IA PI3K. We demonstrated that mutations in
      the helical (E542K, E545A) and kinase domain (H1047R) of p110alpha constitutively
      activate the PI3K-AKT pathway and lead to factor-independent growth of early
      hematopoietic cells. Proliferation and survival of the cells were inhibited in a
      time- and dose-dependent manner using either PI3K or AKT inhibitors. The
      mammalian target of rapamycin (mTOR) was demonstrated to be important for
      mitogenic, but not antiapoptotic signaling of mutant p110alpha. In a syngenic
      mouse model, hematopoietic cells expressing mutated p110alpha induced a leukemia
      like disease characterized by anemia, neoplastic infiltration of hematopoietic
      organs and 90% mortality within 5 weeks, whereas activated mutants of the
      receptor tyrosine kinase c-KIT led to 100% mortality within 10 days. Our data
      show that point mutations in the p110alpha subunit of class IA PI3K confer factor
      independence to hematopoietic cells in vitro and leukemogenic potential in vivo,
      but have lower transforming activity than a deregulated class III receptor
      tyrosine kinase.

PMID- 18317451
TI  - Protein kinase C epsilon confers resistance of MCF-7 cells to TRAIL by Akt
      dependent activation of Hdm2 and downregulation of p53.
AB  - Protein kinase C epsilon (PKC epsilon ) acts as an antiapoptotic protein and
      inhibits tumor necrosis factor-alpha (TNF)-related apoptosis-inducing ligand
      (TRAIL)-induced apoptosis in MCF-7 breast cancer cells. Members of the TNF
      receptor superfamily trigger apoptosis independent of the tumor suppressor
      protein p53, which primarily affects DNA damage-induced apoptosis. We have
      previously shown that PKC epsilon acts upstream of Akt to inhibit receptor
      initiated cell death. Since Akt can regulate p53, we have examined the
      involvement of p53 in PKC epsilon-mediated TRAIL resistance. Overexpression of
      PKC epsilon in MCF-7 cells (MCF-7/PKC epsilon ) caused a decrease in p53 and an
      increase in human homolog of murine double minute 2 (Hdm2) and phospho-Hdm2.
      Depletion of p53 by siRNA attenuated, whereas depletion of Hdm2 enhanced TRAIL
      mediated apoptosis. Knockdown of Akt decreased Hdm2 phosphorylation, increased
      p53 level and potentiated TRAIL-induced cell death. Depletion of epsilon from MCF
      7 cells caused an increase in p53, whereas knockdown of p53 caused a decrease in
      Bid mRNA. Depletion of Akt from MCF-7/PKC epsilon cells resulted in an increase
      in p53 and Bid. These results suggest that PKC epsilon mediates TRAIL resistance
      by Akt-mediated phosphorylation of Hdm2 resulting in suppression of p53
      expression and downregulation of Bid in MCF-7 breast cancer cells.

PMID- 18317452
TI  - Immune escape as a fundamental trait of cancer: focus on IDO.
AB  - Immune escape is a critical gateway to malignancy. The emergence of this
      fundamental trait of cancer represents the defeat of immune surveillance, a
      potent, multi-armed and essential mode of cancer suppression that may influence
      the ultimate clinical impact of an early stage tumor. Indeed, immune escape may
      be a central modifier of clinical outcomes, by affecting tumor dormancy versus
      progression, licensing invasion and metastasis and impacting therapeutic
      response. Although relatively little studied until recently, immune suppression
      and escape in tumors are now hot areas with clinical translation of several new
      therapeutic agents already under way. The interconnections between signaling
      pathways that control immune escape and those that control proliferation,
      senescence, apoptosis, metabolic alterations, angiogenesis, invasion and
      metastasis remain virtually unexplored, offering rich new areas for
      investigation. Here, an overview of this area is provided with a focus on the
      tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO) and its recently
      discovered relative IDO2 that are implicated in suppressing T-cell immunity in
      normal and pathological settings including cancer. Emerging evidence suggests
      that during cancer progression activation of the IDO pathway might act as a
      preferred nodal modifier pathway for immune escape, for example analogous to the
      PI3K pathway for survival or the VEGF pathway for angiogenesis. Small molecule
      inhibitors of IDO and IDO2 heighten chemotherapeutic efficacy in mouse models of
      cancer in a nontoxic fashion and an initial lead compound entered phase I
      clinical trials in late 2007. New modalities in this area offer promising ways to
      broaden the combinatorial attack on advanced cancers, where immune escape
      mechanisms likely provide pivotal support.

PMID- 18317453
TI  - The checkpoint kinases Chk1 and Chk2 regulate the functional associations between
      hBRCA2 and Rad51 in response to DNA damage.
AB  - The cellular response to the introduction of double strand DNA breaks involves
      complexes of protein interactions that govern cell cycle checkpoint arrest and
      repair of the DNA lesions. The checkpoint kinases Chk1 and Chk2 phosphorylate the
      carboxy-terminal domain of hBRCA2, a protein involved in recombination-mediated
      DNA repair (HRR) and replication fork maintenance. Cells deficient in hBRCA2 are
      hypersensitive to DNA damaging agents. Phosphorylation of the residue in hBRCA2
      targeted by the Chk1 and Chk2 kinases regulates its interaction with Rad51.
      Furthermore, the cell line lex1/lex2, which lacks the carboxy-terminal domain
      containing the phosphorylated residue, does not support localization of Rad51 to
      nuclear foci after exposure to UV or treatment with ionizing radiation (IR). The
      data show that either phosphorylation of Rad51 by Chk1 or phosphorylation of the
      carboxy-terminal domain of hBRCA2 by Chk1 or Chk2 plays a critical role in the
      binding of Rad51 to hBRCA2 and the subsequent recruitment of Rad51 to sites of
      DNA damage. While depletion of Chk1 from cells leads to loss of Rad51
      localization to nuclear foci in response to replication arrest, cells lacking
      Chk2 also show a defect in Rad51 localization, but only in presence of double
      strand DNA breaks, indicating that each of these kinases may contribute somewhat
      differently to the formation of Rad51 nucleoprotein filaments depending on the
      type of DNA damage incurred by the cells.

PMID- 18317454
TI  - No impact of NOD2/CARD15 on outcome after SCT.
AB  - Recent studies have pointed towards an association between certain single
      nucleotide polymorphisms (SNPs) in the NOD2/CARD15 gene, and negative outcome of
      Allo-SCT. In this study, 198 patients and their corresponding donors were
      analyzed retrospectively for the occurrence of NOD2/CARD15 mutations to evaluate
      the impact on clinical results after Allo-SCT. In all, 7.6% of the patients and
      11% of the donors were heterozygous for one of three SNPs 8, 12 or 13. Contrary
      to earlier findings, we found no significant impact on incidence of acute GVHD or
      TRM following Allo-SCT. These differences in results could be due to a lower
      mutation frequency in the studied population and/or a lower overall incidence of
      severe GVHD. On the basis of these findings we conclude that a consideration to
      NOD2/CARD15 mutation status is not pertinent when selecting a donor for Allo-SCT
      at our centre.

PMID- 18317455
TI  - An unusual cause of acute abdomen following allogeneic transplantation: a
      zoonotic disease revisited.

PMID- 18317456
TI  - Efficacy of glutamine-supplemented parenteral nutrition on short-term survival
      following allo-SCT: a randomized study.
AB  - Fifty-three patients with hematological malignancies who underwent Allo-SCT from
      HLA-identical siblings were randomly assigned to receive glutamine-enriched
      parenteral nutrition-PN (GlPN, n=27) or standard PN (PN, n=26), in isonitrogenous
      solutions. Deaths (D+100 and D+180), infections, acute GVHD, length of stay, time
      of neutropenia and intestinal permeability (IP) were studied. Ages, gender,
      diagnosis, disease status and treatment variables were equally distributed
      between groups. Survival on D+180 was increased in GlPN (74%) vs PN (46%), P=0.03
      (log-rank), as on D+100 (P=0.05). Most deaths occurred before D+100, especially
      in PN (10/26, 39%) vs GlPN (4/27, 15%). GVHD was the most frequent cause of death
      (8/21, 38%), especially in PN (n=6, five before D+100). Other outcomes were not
      affected. IP was affected on admission, was not affected by glutamine enrichment,
      but consistently worsened throughout the study. Results showed that GlPN was
      efficacious in increasing short-term survival after Allo-SCT. Benefits of
      glutamine seem to be independent of mucosal protection, as IP was not affected by
      its use. A trend to a lower incidence of GVHD deaths may suggest an
      immunomodulatory role of glutamine.

PMID- 18317457
TI  - Rituximab for allo-SCT-associated thrombotic thrombocytopenic purpura.

PMID- 18317458
TI  - Allogeneic donor bone marrow cells recovery and infusion after allogeneic face
      transplantation from the same donor.

PMID- 18317459
TI  - Experienced pleasantness.

PMID- 18317460
TI  - Vibrio cholerae and Aeromonas: do they share a mutual host?
AB  - Species of the genus Aeromonas are native inhabitants of aquatic environments and
      have recently been considered as an emergent human pathogen. It is estimated that
      aeromonads cause up to 13% of reported gastroenteritis cases in the United
      States. Although the autochthonous existence of Aeromonas in the aquatic
      environment has been established, its natural reservoir is as yet unknown.
      Chironomids are closely related to mosquitoes except they do not bite and they
      are the most widely distributed insects in freshwater. They infest drinking water
      systems in Israel and all over the world. Vibrio cholerae inhabit chironomids and
      are able to degrade their egg masses. The degradation of the egg masses is
      followed by failure of the eggs to hatch. In the current study, egg masses from a
      waste stabilization pond and a river in northern Israel were collected and
      cultured during a five-month period. Bacterial colonies were randomly chosen and
      checked for their egg mass degradation abilities. In addition to V. cholerae,
      most of the other isolates that had the ability to degrade the egg masses were
      identified as Aeromonas species, thus, demonstrating that Aeromonas species are
      natural inhabitants of chironomid egg masses. The following virulence-associated
      genes were detected in Aeromonas species that were isolated from chironomid egg
      masses: alt (78%); ahpB (76%); act/aerA/hlyA (65%); fla (59%); pla/lipH3/apl
      1/lip (43%); and ast (2%). These findings indicate that the Aeromonas species
      inhabiting chironomid egg masses pose a potential health risk. Understanding the
      natural reservoir of Aeromonas will help to develop methods to monitor and
      control the bacteria in fresh and drinking water reservoirs and to better
      understand the relationships between chironomids, V. cholerae and Aeromonas
      populations.

PMID- 18317461
TI  - Decreased cortical muscarinic receptors define a subgroup of subjects with
      schizophrenia.
AB  - Schizophrenia is widely acknowledged as being a syndrome, consisting of an
      undefined number of diseases probably with differing pathologies. Although
      studying a syndrome makes the identification of an underlying pathology more
      difficult; neuroimaging, neuropsychopharmacological and post-mortem brain studies
      all implicate muscarinic acetylcholine receptors (CHRM) in the pathology of the
      disorder. We have established that the CHRM1 is selectively decreased in the
      dorsolateral prefrontal cortex of subjects with schizophrenia. To expand this
      finding, we wanted to ascertain whether decreased cortical CHRMs might (1) define
      a subgroup of schizophrenia and/or (2) be related to CHRM1 genotype. We assessed
      cortical [(3)H]pirenzepine binding and sequenced the CHRM1 in 80 subjects with
      schizophrenia and 74 age sex-matched control subjects. Kernel density estimation
      showed that [(3)H]pirenzepine binding in BA9 divided the schizophrenia, but not
      control, cohort into two distinct populations. One of the schizophrenia cohorts,
      comprising 26% of all subjects with the disorder, had a 74% reduction in mean
      cortical [(3)H]pirenzepine binding compared to controls. We suggest that these
      individuals make up 'muscarinic receptor-deficit schizophrenia' (MRDS). The MRDS
      could not be separated from other subjects with schizophrenia by CHRM1 sequence,
      gender, age, suicide, duration of illness or any particular drug treatment. Being
      able to define a subgroup within schizophrenia using a central biological
      parameter is a pivotal step towards understanding the biochemistry underlying at
      least one form of the disorder and may represent a biomarker that can be used in
      neuroimaging.

PMID- 18317462
TI  - Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar
      disorder.
AB  - The neuronal PAS domain 3 (NPAS3) gene encodes a neuronal transcription factor
      that is implicated in psychiatric disorders by the identification of a human
      chromosomal translocation associated with schizophrenia and a mouse knockout
      model with behavioural and hippocampal neurogenesis defects. To determine its
      contribution to the risk of psychiatric illness in the general population, we
      genotyped 70 single-nucleotide polymorphisms across the NPAS3 gene in 368
      individuals with bipolar disorder, 386 individuals with schizophrenia and 455
      controls. Modestly significant single-marker and global and individual haplotypes
      were identified in four discrete regions of the gene. The presence of both risk
      and protective haplotypes at each of these four regions indicated locus and
      allelic heterogeneity within NPAS3 and suggested a model whereby interactions
      between variants across the gene might contribute to susceptibility to illness.
      This was supported by predicting the most likely haplotype for each individual at
      each associated region and then calculating an NPAS3-mediated 'net genetic load'
      value. This value differed significantly from controls for both bipolar disorder
      (P=0.0000010) and schizophrenia (P=0.0000012). Logistic regression analysis also
      confirmed the combinatorial action of the four associated regions on disease
      risk. In addition, sensitivity/specificity plots showed that the extremes of the
      genetic loading distribution possess the greatest predictive power-a feature
      suggesting multiplicative allele interaction. These data add to recent evidence
      that the combinatorial analysis of a number of relatively small effect size
      haplotypes may have significant power to predict an individual's risk of a
      complex genetic disorder such as psychiatric illness.

PMID- 18317463
TI  - Effects of the G(-656)A variant on CREB1 promoter activity in a neuronal cell
      line: interactions with gonadal steroids and stress.
AB  - Major depressive disorder (MDD) constitutes a major public health problem
      worldwide and affects women twice as frequently as men. Previous genetic studies
      have revealed significant evidence of linkage of the cAMP-responsive element
      binding protein 1 (CREB1) gene region (2q33-35) to mood disorders among women
      from families with recurrent, early-onset MDD (RE-MDD), a severe and familial
      subtype of MDD. A rare G-to-A transition at position -656 in the CREB1 promoter
      co-segregates with mood disorders in women from these families, implicating CREB1
      as a sex-related susceptibility gene for unipolar mood disorders. In the current
      study, the functional significance of the CREB1 promoter variant was determined
      using transfection experiments that employed plasmid constructs containing the
      wild-type or variant CREB1 promoters coupled to a reporter gene. The results
      support the hypothesis that the A(-656) allele contributes to the development of
      MDD in women through selective alteration of CREB1 promoter activity by female
      gonadal steroids in noradrenergic neuronal cells. Furthermore, exaggeration of
      these effects during a simulated stress condition may be relevant to reported
      gene-environment interactions that contribute to the emergence of MDD in clinical
      populations.

PMID- 18317464
TI  - DISC1 association, heterogeneity and interplay in schizophrenia and bipolar
      disorder.
AB  - Disrupted in schizophrenia 1 (DISC1) has been associated with risk of
      schizophrenia, schizoaffective disorder, bipolar disorder, major depression,
      autism and Asperger syndrome, but apart from in the original translocation
      family, true causal variants have yet to be confirmed. Here we report a
      harmonized association study for DISC1 in European cohorts of schizophrenia and
      bipolar disorder. We identify regions of significant association, demonstrate
      allele frequency heterogeneity and provide preliminary evidence for modifying
      interplay between variants. Whereas no associations survived permutation analysis
      in the combined data set, significant corrected associations were observed for
      bipolar disorder at rs1538979 in the Finnish cohorts (uncorrected P=0.00020;
      corrected P=0.016; odds ratio=2.73+/-95% confidence interval (CI) 1.42-5.27) and
      at rs821577 in the London cohort (uncorrected P=0.00070; corrected P=0.040; odds
      ratio=1.64+/-95% CI 1.23-2.19). The rs821577 single nucleotide polymorphism (SNP)
      showed evidence for increased risk within the combined European cohorts (odds
      ratio=1.27+/-95% CI 1.07-1.51), even though significant corrected association was
      not detected (uncorrected P=0.0058; corrected P=0.28). After conditioning the
      European data set on the two risk alleles, reanalysis revealed a third
      significant SNP association (uncorrected P=0.00050; corrected P=0.025). This SNP
      showed evidence for interplay, either increasing or decreasing risk, dependent
      upon the presence or absence of rs1538979 or rs821577. These findings provide
      further support for the role of DISC1 in psychiatric illness and demonstrate the
      presence of locus heterogeneity, with the effect that clinically relevant genetic
      variants may go undetected by standard analysis of combined cohorts.

PMID- 18317465
TI  - Involvement of the PRKCB1 gene in autistic disorder: significant genetic
      association and reduced neocortical gene expression.
AB  - Protein kinase C enzymes play an important role in signal transduction,
      regulation of gene expression and control of cell division and differentiation.
      The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta
      gene (PRKCB1), previously found to be associated with autism. We performed a
      family-based association study in 229 simplex and 5 multiplex families, and a
      postmortem study of PRKCB1 gene expression in temporocortical gray matter
      (BA41/42) of 11 autistic patients and controls. PRKCB1 gene haplotypes are
      significantly associated with autism (P<0.05) and have the autistic endophenotype
      of enhanced oligopeptiduria (P<0.05). Temporocortical PRKCB1 gene expression was
      reduced on average by 35 and 31% for the PRKCB1-1 and PRKCB1-2 isoforms (P<0.01
      and <0.05, respectively) according to qPCR. Protein amounts measured for the
      PKCbetaII isoform were similarly decreased by 35% (P=0.05). Decreased gene
      expression characterized patients carrying the 'normal' PRKCB1 alleles, whereas
      patients homozygous for the autism-associated alleles displayed mRNA levels
      comparable to those of controls. Whole genome expression analysis unveiled a
      partial disruption in the coordinated expression of PKCbeta-driven genes,
      including several cytokines. These results confirm the association between autism
      and PRKCB1 gene variants, point toward PKCbeta roles in altered epithelial
      permeability, demonstrate a significant downregulation of brain PRKCB1 gene
      expression in autism and suggest that it could represent a compensatory
      adjustment aimed at limiting an ongoing dysreactive immune process. Altogether,
      these data underscore potential PKCbeta roles in autism pathogenesis and spur
      interest in the identification and functional characterization of PRKCB1 gene
      variants conferring autism vulnerability.

PMID- 18317466
TI  - COMT genotype predicts cortical-limbic D1 receptor availability measured with
      [11C]NNC112 and PET.
AB  - A common polymorphism (val158met) in the gene encoding catechol-O
      methyltransferase (COMT) has been shown to affect dopamine (DA) tone in cortex
      and cortical functioning. D1 receptors are the main DA receptors in the cortex,
      and studies have shown that decreased levels of cortical DA are associated with
      upregulation of D1 receptor availability, as measured with the positron-emission
      tomography (PET) radiotracer [11C]NNC112. We compared [11C]NNC 112 binding in
      healthy volunteers homozygous for the Val allele compared with Met carriers.
      Subjects were otherwise matched for parameters known to affect [11C]NNC 112
      binding. Subjects with Val/Val alleles had significantly higher cortical [11C]NNC
      112 binding compared with Met carriers, but did not differ in striatal binding.
      These results confirm the prominent role of COMT in regulating DA transmission in
      cortex but not striatum, and the reliability of [11C]NNC 112 as a marker for low
      DA tone as previously suggested by studies in patients with schizophrenia.

PMID- 18317467
TI  - Face-brain asymmetry in autism spectrum disorders.
AB  - The heterogeneity of autism spectrum disorders (ASDs) confounds attempts to
      identify causes and pathogenesis. Identifiable endophenotypes and reliable
      biomarkers within ASDs would help to focus molecular research and uncover genetic
      causes and developmental mechanisms. We used dense surface-modelling techniques
      to compare the facial morphology of 72 boys with ASD and 128 first-degree
      relatives to that of 254 unrelated controls. Pattern-matching algorithms were
      able to discriminate between the faces of ASD boys and those of matched controls
      (AUC=0.82) and also discriminate between the faces of unaffected mothers of ASD
      children and matched female controls (AUC=0.76). We detected significant facial
      asymmetry in boys with ASD (P<0.01), notably depth-wise in the supra- and
      periorbital regions anterior to the frontal pole of the right hemisphere of the
      brain. Unaffected mothers of children with ASD display similar significant facial
      asymmetry, more exaggerated than that in matched controls (P<0.03) and, in
      particular, show vertical asymmetry of the periorbital region. Unaffected fathers
      of children with ASD did not show facial asymmetry to a significant degree
      compared to controls. Two thirds of unaffected male siblings tested were
      classified unseen as more facially similar to unrelated boys with ASD than to
      unrelated controls. These unaffected male siblings and two small groups of girls
      with ASD and female siblings, all show overall directional asymmetry, but without
      achieving statistical significance in two-tailed t-tests of individual asymmetry
      of ASD family and matched control groups. We conclude that previously identified
      right dominant asymmetry of the frontal poles of boys with ASD could explain
      their facial asymmetry through the direct effect of brain growth. The atypical
      facial asymmetry of unaffected mothers of children with ASD requires further
      brain studies before the same explanation can be proposed. An alternative
      explanation, not mutually exclusive, is a simultaneous and parallel action on
      face and brain growth by genetic factors. Both possibilities suggest the need for
      coordinated face and brain studies on ASD probands and their first-degree
      relatives, especially on unaffected mothers, given that their unusual facial
      asymmetry suggests an ASD susceptibility arising from maternal genes.

PMID- 18317469
TI  - Abnormal postprandial PYY response in insulin sensitive nondiabetic subjects with
      a strong family history of type 2 diabetes.
AB  - OBJECTIVE: Gut-derived hormone peptide YY (PYY) is low in subjects with obesity
      and type 2 diabetes (T2D). However, it is unknown whether this is a primary
      defect or a consequence of metabolic disturbances. In this study, we aimed to
      assess whether low fasting and postprandial PYY secretion is an early defect,
      potentially promoting the development of obesity and T2D, and whether it is
      modified by macronutrient content. DESIGN: Prospective cross-sectional cohort
      study. SUBJECTS: Nine individuals with a strong family history of T2D (REL) and
      seven age and adiposity matched individuals with no family history of T2D (CON).
      INTERVENTIONS: Metabolic studies including hyperinsulinemic-euglycemic clamp,
      dual X-ray absorptiometry and two meal tests containing 1000 kcal with an either
      high fat (76%) or high carbohydrate (76%) content. MAIN OUTCOME MEASURES: Fasting
      and postprandial PYY levels were measured and analyzed for potential correlations
      with markers for adiposity and insulin resistance. RESULTS: Insulin sensitivity
      was not different between REL and CON. Fasting glucose, insulin, triglycerides
      and PYY were also not different between groups. However, the postprandial
      incremental area under curve (AUC) of PYY was significantly lower in REL after
      the high carbohydrate (HCHO) meal (+27.3 vs +60.6% increase from baseline,
      P=0.038). The AUC of insulin during HCHO meal correlated negatively with both AUC
      and fasting level of PYY (r=-0.58 and -0.60, respectively, P<0.05). CONCLUSIONS:
      A blunted postprandial PYY secretion is observed in a very early stage in the
      development of T2D in genetically susceptible individuals. This defect precedes
      the presence of insulin resistance and adiposity, and could therefore predispose
      to the development of T2D.

PMID- 18317468
TI  - Whole-genome association study of bipolar disorder.
AB  - We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1
      disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program
      for Bipolar Disorder and the University College London sample collections with
      successful genotyping for 372,193 single nucleotide polymorphisms (SNPs). Our
      strongest single SNP results are found in myosin5B (MYO5B; P=1.66 x 10(-7)) and
      tetraspanin-8 (TSPAN8; P=6.11 x 10(-7)). Haplotype analysis further supported
      single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor
      receptor (MYO5B; P=2.04 x 10(-8), TSPAN8; P=7.57 x 10(-7) and EGFR; P=8.36 x 10(
      8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n=409
      trios) and University of Edinburgh case-control samples (n=365 cases, 351
      controls) that did not provide independent replication after correction for
      multiple testing. A comparison of our strongest associations with the genome-wide
      scan of 1868 patients with BP disorder and 2938 controls who completed the scan
      as part of the Wellcome Trust Case-Control Consortium indicates concordant
      signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C
      subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of
      agreement between studies emphasizes that susceptibility alleles are likely to be
      modest in effect size and require even larger samples for detection.

PMID- 18317470
TI  - NYD-SP18 is associated with obesity in the NHLBI Family Heart Study.
AB  - OBJECTIVE: The NHLBI Family Heart Study (FHS) genome-wide linkage scan identified
      a region of chromosome 7q with a logarithm of odds score of 4.9 for body mass
      index (BMI). DESIGN: We report the results of fine mapping the linkage peak using
      1020 single nucleotide polymorphisms (SNPs) to test for association to obesity in
      families exhibiting linkage to chromosome 7. Association observed in linked
      families (284 obese cases/381 controls) was examined in an independent set of
      unrelated FHS participants (172 obese cases/308 controls) to validate the
      observed association. Two dichotomous obesity phenotypes were studied based on
      clinical BMI cutoffs and the sex-specific distribution of both BMI and leptin
      levels. RESULTS: Using a P-value of 0.01 as criteria for association in the
      linked families, a P-value of 0.05 as criteria for association in the unrelated
      sample, and requiring consistency in the direction of the effect of the minor
      allele between the two samples, we identified two coding SNPs in the NYD-SP18
      gene with minor alleles increasing the risk of obesity. Adjustment for exercise,
      smoking and FTO genotype did not influence the result in linked families, but
      improved the result in the unrelated sample. Carrying a minor allele of the
      nonsynonymous SNP rs6971091 conferred an odds ratio of at least 2 for obesity
      defined by both BMI and leptin levels. CONCLUSION: The effect of the NYD-SP18 SNP
      on obesity was larger than the effect of FTO in FHS families. Publicly available
      results from genome-wide association studies support the association between NYD
      SP18 and BMI. The NYD-SP18 gene is described as testes development related, but
      little is known about the gene's function or the mechanism by which it may
      influence risk for obesity.

PMID- 18317471
TI  - Perceptions of weight discrimination: prevalence and comparison to race and
      gender discrimination in America.
AB  - OBJECTIVE: Limited data are available on the prevalence and patterns of body
      weight discrimination from representative samples. This study examined
      experiences of weight/height discrimination in a nationally representative sample
      of US adults and compared their prevalence and patterns with discrimination
      experiences based on race and gender. METHOD AND PROCEDURES: Data were from the
      National Survey of Midlife Development in the United States, a 1995-1996
      community-based survey of English-speaking adults aged 25-74 (N=2290). Reported
      experiences of weight/height discrimination included a variety of institutional
      settings and interpersonal relationships. Multivariate regression analyses were
      used to predict weight/height discrimination controlling for sociodemographic
      characteristics and body weight status. RESULTS: The prevalence of weight/height
      discrimination ranged from 5% among men to 10% among women, but these average
      percentages obscure the much higher risk of weight discrimination among heavier
      individuals (40% for adults with body mass index (BMI) of 35 and above). Younger
      individuals with a higher BMI had a particularly high risk of weight/height
      discrimination regardless of their race, education and weight status. Women were
      at greater risk for weight/height discrimination than men, especially women with
      a BMI of 30-35 who were three times more likely to report weight/height
      discrimination compared to male peers of a similar weight. DISCUSSION:
      Weight/height discrimination is prevalent in American society and is relatively
      close to reported rates of racial discrimination, particularly among women. Both
      institutional forms of weight/height discrimination (for example, in employment
      settings) and interpersonal mistreatment due to weight/height (for example, being
      called names) were common, and in some cases were even more prevalent than
      discrimination due to gender and race.

PMID- 18317472
TI  - Vegetable-rich food pattern is related to obesity in China.
AB  - OBJECTIVE: To investigate the association between a vegetable-rich food pattern
      and obesity among Chinese adults. DESIGN: A food pattern rich in vegetables is
      associated with lower risk of obesity and non-communicable chronic disease in
      Western countries. A similar food pattern is found in the Chinese population but
      the cooking method is different. A cross-sectional household survey of 2849 men
      and women aged 20 years and over was undertaken in 2002 in Jiangsu Province
      (response rate, 89.0%). Food intake was assessed by food frequency questionnaire.
      Factor analysis was used to identify food patterns. Nutrient intake was measured
      by food weighing plus consecutive individual 3-day food records. Height, weight
      and waist circumference were measured. RESULTS: The prevalence of general obesity
      (BMI > or =28 kg m(-2)) was 8.0% in men and 12.7% in women, central obesity was
      19.5% (> or =90 cm) and 38.2% (> or =80 cm), respectively. A four-factor solution
      explained 28.5% of the total variance in food frequency intake. The vegetable
      rich food pattern (whole grains, fruits and vegetables) was positively associated
      with vegetable oil and energy intake. Prevalence of obesity/central obesity
      increased across the quartiles of vegetable-rich food pattern. After adjusting
      for sociodemographic factors and four distinct food patterns, the vegetable-rich
      pattern was independently associated with obesity. Compared with the lowest
      quartile of vegetable-rich pattern, the highest quartile had higher risk of
      general obesity (men, prevalence ratio (PR): 1.82, 95% confidence interval (CI):
      1.05-3.14; women, PR: 2.25, 95% CI: 1.45-3.49). CONCLUSION: The vegetable-rich
      food pattern was associated with higher risk of obesity/central obesity in
      Chinese adults in both genders. This association can be linked to the high intake
      of energy due to generous use of oil for stir-frying the vegetables.

PMID- 18317473
TI  - Genome-wide scan revealed genetic loci for energy metabolism in Hispanic children
      and adolescents.
AB  - OBJECTIVE: Genome-wide scans were conducted in search for genetic locations
      linked to energy expenditure and substrate oxidation in children. DESIGN:
      Pedigreed data of 1030 Hispanic children and adolescents were from the Viva La
      Familia Study which was designed to investigate genetic and environmental risk
      factors for the development of obesity in Hispanic families. A respiratory
      calorimeter was used to measure 24-h total energy expenditure (TEE), basal
      metabolic rate (BMR), sleep metabolic rate (SMR), 24-h respiratory quotient
      (24RQ), basal metabolic respiratory quotient (BMRQ) and sleep respiratory
      quotient (SRQ). Protein, fat and carbohydrate oxidation (PROOX, FATOX and CHOOX,
      respectively) were also estimated. All participants were genotyped for 384 single
      tandem repeat markers spaced an average of 10 cM apart. Computer program SOLAR
      was used to perform the genetic linkage analyses. RESULTS: Significant linkage
      for TEE was detected on chromosome 1 near marker D1S2841, with a logarithm of the
      odds (LOD) score of 4.0. SMR, BMRQ and PROOX were associated with loci on
      chromosome 18, 17 and 9, respectively, with LOD scores of 4.88, 3.17 and 4.55,
      respectively. A genome-wide scan of SMR per kg fat-free mass (SpFFM) peaked in
      the same region as SMR on chromosome 18 (LOD, 5.24). Suggestive linkage was
      observed for CHOOX and FATOX. Several candidate genes were found in the above
      chromosomal regions including leptin receptor (LEPR). CONCLUSION: Regions on
      chromosomes 1, 9, 17 and 18 harbor genes affecting variation in energy
      expenditure and substrate oxidation in Hispanic children and adolescents.

PMID- 18317474
TI  - Do you see what I see? Weight status misperception and exposure to obesity among
      children and adolescents.
AB  - OBJECTIVE: Obesity prevention in childhood is important. However, changing
      children's lifestyle behaviors to reduce overweight is a substantial challenge.
      Accurately perceiving oneself as overweight/obese has been linked to greater
      motivation to change lifestyle behaviors. Children and adolescents may be less
      likely to perceive themselves as overweight/obese if they are exposed to
      overweight/obese people in their immediate environments. This study examined
      whether youth who are exposed to overweight parents and schoolmates were more
      likely to misperceive their own weight status. DESIGN: The Quebec Child and
      Adolescent Health and Social Survey was a provincially representative, school
      based survey of children and adolescents conducted between January and May 1999.
      SUBJECTS: 3665 children and adolescents (age 9, n=1267; age 13, n=1186; age 16,
      n=1212) from 178 schools. Mean body mass index (BMI) was 17.5, 20.6 and 22.2
      kg/m(2), respectively. MEASUREMENTS: The misperception score was calculated as
      the standardized difference between self-perception of weight status (Stunkard
      Body Rating Scale) and actual BMI (from measured height and weight). Exposure to
      obesity was based on parent and schoolmate BMI. RESULTS: Overweight and obese
      youth were significantly more likely to misperceive their weight compared with
      non-overweight youth (P<0.001). Multilevel modeling indicated that greater parent
      and schoolmate BMI were significantly associated with greater misperception
      (underestimation) of weight status among children and adolescents. CONCLUSION:
      Children and adolescents who live in environments in which people they see on a
      daily basis, such as parents and schoolmates, are overweight/obese may develop
      inaccurate perceptions of what constitutes appropriate weight status. Targeting
      misperception may facilitate the adoption of healthy lifestyle behaviors and
      improve the effectiveness of obesity prevention interventions.

PMID- 18317475
TI  - Mechanisms of disease: ion channel remodeling in the failing ventricle.
AB  - In an attempt to compensate for compromised hemodynamics in heart failure,
      neurohumoral mechanisms are activated that trigger fundamental changes in gene
      expression and in protein processing, trafficking and post-translational
      regulation, resulting in myocyte hypertrophy. Unfortunately, over time these
      changes become maladaptive, predisposing to myocyte loss, chamber dilatation,
      interstitial hyperplasia and intercellular uncoupling. Intrinsic and peripheral
      responses to mechanical dysfunction alter the expression and function of key ion
      channels and calcium-handling proteins, thereby remodeling the cellular action
      potential and the intracellular calcium transient. This electrophysiological
      remodeling renders the heart more vulnerable to ventricular arrhythmias that
      underlie sudden cardiac death. In this Review, we consider key ventricular ionic
      changes that are associated with heart failure, with the intention of identifying
      molecular targets for antiarrhythmic therapy.

PMID- 18317476
TI  - Neglected diseases in cardiology: a call for urgent action.

PMID- 18317477
TI  - Screening to identify individuals at high risk of developing diabetic foot
      ulcers.

PMID- 18317478
TI  - A fixed combination of perindopril and indapamide reduces the risk of vascular
      outcomes in type 2 diabetes mellitus.

PMID- 18317479
TI  - The use of interleukin-1-receptor antagonists in the treatment of diabetes
      mellitus.

PMID- 18317480
TI  - Does radioiodine therapy for hyperthyroidism increase long-term morbidity?

PMID- 18317481
TI  - Sacral nerve stimulation as an option for the treatment of faecal incontinence in
      patients suffering from cauda equina syndrome.
AB  - STUDY DESIGN: Retrospective clinical study with 1-year follow-up. OBJECTIVES:
      Treatment of faecal incontinence by permanent sacral nerve stimulation (SNS) in
      patients suffering from cauda equina syndrome (CES). SETTING: Klosterneuburg,
      Austria. BACKGROUND AND PURPOSE: A flaccid paresis of the sphincter ani muscle
      and the pelvic floor combined with faecal incontinence can occur in patients
      suffering from CES as a result of a trauma in the region of the lumbar spine. If
      the incontinence cannot be managed by the use of laxatives or anal tampons, the
      patient is restricted in his/her quality of life. Thus, it was our aim to improve
      sphincter function and anal sensitivity to achieve voluntary rectal defaecation.
      MATERIALS AND METHODS: The functional integrity of at least one sacral root (S2
      S4) was determined through percutaneous nerve evaluation (PNE). Following this
      analysis, a period of external temporary SNS was performed to evaluate the
      functional effect. If there was a decrease in the number of episodes of faecal
      incontinence during this evaluation period, a neurostimulation device (InterStim;
      Medtronic) was implanted. PATIENTS: A total of 11 patients suffering from flaccid
      paresis of the anal sphincter muscle and faecal incontinence caused by CES
      underwent PNE, which was successful in 8 patients. Two of these patients were
      eliminated from the procedure at the end of the temporary SNS period, one patient
      refused the permanent implantation. Therefore, five patients proceeded to
      permanent implantation, which led to an improved continence in all the cases.
      DISCUSSION: In the synopsis of the preoperative proctologic and neurological
      findings, successful electric stimulation of the sacral roots can be expected in
      incomplete CES. In the case of flaccid paresis of the anal sphincter muscles
      caused by an incomplete CES, permanent SNS offers a promising option for the
      treatment of faecal incontinence. .

PMID- 18317482
TI  - Decreased levels of testosterone and gonadotrophins in men with long-standing
      tetraplegia.
AB  - STUDY DESIGN: Blood samples were frequently collected during a 24-h period from
      six tetraplegic men. The results were compared with those of eight able-bodied
      controls. OBJECTIVE: Previous studies have reported conflicting results regarding
      the plasma concentrations of testosterone, luteinizing hormone (LH) and follicle
      stimulating hormone (FSH) in tetraplegia. The objective of this study was to
      examine the pituitary-gonadal axis by determining the plasma concentrations and
      circadian variations of these hormones in men with long-standing tetraplegia.
      SETTING: Sunnaas Hospital, Norway. METHODS: The plasma concentrations of hormones
      were measured with standardized assays. RESULTS: All three hormones and free
      testosterone index were decreased in the tetraplegic subjects compared with the
      able-bodied controls (P<0.05). We also determined the morning levels of hormones
      with regulatory effects on testosterone, LH and FSH. Whereas plasma leptin was
      significantly higher in the tetraplegic group, no significant differences in the
      morning plasma values for insulin, SHBG, GH or IGF-1, or in the 24-h urine
      concentrations of cortisol were detected between the two groups. The plasma
      concentration of LH displayed a circadian variation (P<0.05) in the tetraplegic
      group, but not among the able-bodied. No circadian variation was noted for the
      plasma concentrations of testosterone and FSH in either group. CONCLUSION: Our
      data indicate that, over time, tetraplegic male subjects might be at risk of
      developing hypogonadism.

PMID- 18317483
TI  - Statistics and the prostate gland.

PMID- 18317484
TI  - Neuropathic bladder dysfunction in patients with motor complete and sensory
      incomplete spinal cord lesion.
AB  - STUDY DESIGN: A retrospective study of patients with motor complete spinal cord
      lesion and somatosensory preservation (American Spinal Injury Association (ASIA)
      impairment scale B). OBJECTIVE: To determine whether neuropathic bladder
      dysfunction is more or less severe with more or fewer complications in patients
      with somatosensory preservation. SETTING: 2nd Department of Physical and
      Rehabilitation Medicine, Neuropathic Bladder Unit, National Rehabilitation
      Center, EIAA, Athens, Greece. METHODS: The classification of spinal cord injured
      patients was determined according to ASIA protocol. All patients underwent
      urodynamics and retrograde cystography, with a follow-up period of at least 18
      months. The study sample consisted of 154 patients: 28 ASIA B patients compared
      with 126 ASIA A patients. We analyzed 140 traumatic and 14 nontraumatic lesions
      for (1) specific type of neuropathic bladder, (2) detrusor overactivity volume
      and pressure, (3) bladder compliance, (4) vesicoureteric reflux, (5) formation of
      bladder stones, (6) method of bladder emptying and (7) daily dose of
      anticholinergics needed to achieve safe bladder function. We also studied the
      presence of spasticity, autonomic dysreflexia and pain syndrome. RESULTS:
      Statistically significant differences were found between ASIA A and B patients in
      daily dose of anticholinergics needed to achieve safe bladder function, in the
      incidence of incontinence episodes and in formation of bladder stones.
      CONCLUSION: Patients with somatosensory incomplete lesion of spinal cord seem to
      have an advantage in the management of neuropathic bladder dysfunction (fewer
      anticholinergics needed, fewer incontinence episodes and fewer bladder stones).

PMID- 18317485
TI  - Residence and quality of life determinants for adults with tetraplegia of
      traumatic spinal cord injury etiology.
AB  - STUDY DESIGN: Cross-sectional analysis of individual interviews with a
      convenience sample of persons living with tetraplegia. OBJECTIVES: To describe
      patterns of residence among persons living with tetraplegia following discharge
      from initial acute medical care after spinal cord injury, decision-making process
      for each residence move and quality of life determinants at different residence
      types. SETTING: California and Minnesota, United States. METHODS: A total of 22
      adults with traumatic spinal cord injury tetraplegia were interviewed about their
      residence histories, the residence decision-making process for each move, and
      positive and negative features at each residence at which they had lived.
      RESULTS: Information, money, insurance, accessibility, intimate relationships and
      personal assistants had the strongest influence over residence location, with
      insufficient information and finances demonstrating particularly strong
      influences. Participants frequently viewed parents' homes as an 'only option,'
      'place of refuge' or 'stunting' environment. They viewed own homes as 'only
      options' or ways to achieve quality of life improvements, and other institutions
      as 'only options' or 'stepping-stones' to independent living. CONCLUSION: Further
      research is needed to examine decision-making across multiple moves over the
      course of the lives of persons living with tetraplegia, particularly examining
      the roles of inadequate information and finances as inhibitors of freedom of
      choice.

PMID- 18317486
TI  - Isolated intraspinal germinoma in a child with congenital adrenal hyperplasia.
AB  - STUDY DESIGN: Case report. OBJECTIVE: To report an intramedullary germinoma
      associated with congenital adrenal hyperplasia (CAH). METHOD: We report a 14-year
      old white male with CAH who was found to have an intramedullary germinoma of the
      conus medullaris. Presentation and evaluation were for progressive urinary
      incontinence. A brief review of relevant literature was presented. RESULTS: Cases
      where germinomas have occurred simultaneously with CAH have been identified
      intracranially, but to our knowledge, this is the first case of CAH and
      intramedullary spinal cord germinoma occurring simultaneously. CONCLUSION:
      Although rare, primary intramedullary germinomas do occur. The association
      between CAH and spinal cord germinoma should be considered by clinicians.

PMID- 18317487
TI  - Posterior decompression and stabilization for metastatic compression of the
      thoracic spinal cord: is this procedure still state of the art?
AB  - STUDY DESIGN: Retrospective study utilizing the standard patient data
      documentation of a spinal cord injury (SCI) unit. OBJECTIVE: To examine the
      efficacy and outcome of posterior decompression and stabilization for metastatic
      cord compression. SETTING: Orthopedic university hospital with large SCI unit.
      METHODS: The 34 consecutive patients who had presented with symptoms of spinal
      cord compression due to metastatic disease and progressive neurologic deficit
      were treated using a uniform surgical approach (posterior decompression and
      stabilization). After surgery, all treatment options available in a full-featured
      SCI unit were applied as necessary and suitable. Outcome was rated concerning
      neurologic function (American Spinal Injury Association, ASIA), functional status
      (Functional Independence Measure) and pain. The results were compared to the
      published results, focusing on publications describing results of anterior
      surgical approaches to the spine. RESULTS: Evaluation of the results of the ASIA
      exams showed that progression of the neurologic deficit could be stopped in the
      majority of cases-however recovery of neurologic function was rare. The
      functional status could be improved markedly and good pain reduction was
      achieved. CONCLUSION: I mmediate surgery can be recommended if the general
      condition of the patient warrants surgical intervention. Using accepted standards
      of documentation for SCI, a clear perspective of the results that can be expected
      is provided. Comparing the results of this study with the current literature
      there is no evidence that anterior approaches are superior.

PMID- 18317488
TI  - Treatment of neurogenic bowel dysfunction using transanal irrigation: a
      multicenter Italian study.
AB  - STUDY DESIGN: Thirty-six patients with unsatisfactory treatment of neurogenic
      bowel dysfunctions (NBD) were enrolled from Spinal Units and Rehabilitation
      Centers in Italy. Treatment was for 3 weeks using a newly developed integrated
      system with an enema continence catheter for transanal irrigation (Peristeen,
      Coloplast A/S Kokkedal Denmark). OBJECTIVES: To evaluate the effects of Peristeen
      Anal Irrigation on NBD and patient quality of life (QoL). SETTING: Italy.
      METHODS: Lesion level, ambulatory status and hand functionality were determined
      in all patients. NBD symptoms and QoL were evaluated before and after treatment,
      using a specific questionnaire. Statistical analysis was performed using McNemar
      Test and Sign Test. RESULTS: Thirty-six patients were enrolled, and 32 patients
      completed the study. At the end of the treatment, 28.6% of patients reduced or
      eliminated their use of pharmaceuticals. Twenty-four patients became less
      dependent on their caregiver. There was a significant increase in patients'
      opinion of their intestinal functionality (P=0.001), QoL score (P=0.001) and
      their answers regarding their degree of satisfaction (P=0.001). A successful
      outcome was recorded for 68% of patients with fecal incontinence, and for 63% of
      patients with constipation. CONCLUSION: Peristeen Anal Irrigation is a simple
      therapeutic method for managing NBD and improving QoL. It should be considered as
      the treatment of choice for NBD, playing a role in the neurogenic bowel analogous
      to that of intermittent clean catheterization in bladder treatment.

PMID- 18317489
TI  - Outcomes of lower urinary and bowel function in meningomyelocele patients with
      augmentation enterocystoplasty.
AB  - OBJECTIVES: We evaluated the outcomes of augmentation ileocystoplasty in video
      urodynamics (V-UDS) and questionnaires related to bowel and urinary function.
      METHODS: In 22 meningomyelocele (MMC) patients (11 male and 11 female, a mean age
      at surgery 14.4 years) who underwent augmentation ileocystoplasties, V-UDS was
      performed before and at a median of 15 months (6-120 months) after the surgery
      and the questionnaires were answered at a median of 7.1 years (1.1-14.5 years)
      after surgery. RESULTS: Concomitant procedures of urethral sling in four,
      cecostomy in four and ureteral reimplantation in two were performed at
      augmentation ileocystoplasty. V-UDS showed a significant improvement after the
      surgery in bladder capacity, bladder compliance and detrusor overactivity.
      Vesicoureteral reflux (VUR) disappeared after the surgery in 16 of 19 ureters
      with VUR. Although questionnaire for urinary condition using International
      Consultation on Incontinence Questionnaire-Short Form demonstrated that 80% of
      patients were completely free from urinary incontinence after surgery, more than
      a half of patients had persistent or deteriorated bowel function such as urgency
      of bowel movement and fecal incontinence in questionnaires for bowel function.
      Even with complaints in bowel function, more than 80% of MMC patients had a high
      level of satisfaction with augmentation enterocystoplasty in overall quality of
      life (QOL). CONCLUSIONS: Benefits of augmentation ileocystoplasty were maintained
      in urodynamic parameters as well as urinary continence. Although augmentation
      ileocystoplasty generally provides high QOL for MMC patients refractory to
      conservative therapies, an advance of fecal management can make MMC patients' QOL
      superior to a current state.

PMID- 18317490
TI  - Microglia inhibition is a target of mild hypothermic treatment after the spinal
      cord injury.
AB  - STUDY DESIGN: A basic study using a spinal cord injury (SCI) model in rats.
      OBJECTIVES: The effect of mild hypothermic treatment on histological changes and
      motor function after a rat spinal cord compression injury was assessed. METHODS:
      Mild spinal cord compression was performed at the eleventh thoracic vertebral
      level by a 20 g weight for 20 min. Rats in the mild hypothermic model were kept
      at a body temperature of 33 degrees C and rats in the normothermic group were
      kept at 37 degrees C for 1 h from beginning of compression. Motor function was
      evaluated by measuring the frequency of standing. Microglia were stained by
      isolectin B4 and observed in the compressed portion of the spinal cord. The
      amount of tumor necrosis factor-alpha (TNF-alpha) in the compressed spinal cord
      was measured by the ELISA method. RESULTS: In the normothermic rats, microglia
      proliferated up to 72 h after the compression. Proliferation was substantially
      inhibited at 48 and 72 h after compression in the hypothermic rats. The motor
      function of the hypothermic rats improved at 48 and 72 h after the compression,
      whereas no improvement was seen in the normothermic rats. The amount of TNF-alpha
      in the compressed portion of the spinal cord was lower in hypothermic rats
      compared with normothermic rats throughout the experiment. CONCLUSIONS: These
      results suggest that hypothermic treatment is effective for the amelioration of
      delayed motor dysfunction via inhibition of microglial inflammatory responses.

PMID- 18317491
TI  - Incidence and profile of spinal tuberculosis in patients at the only public
      hospital admitting such patients in KwaZulu-Natal.
AB  - STUDY DESIGN: A retrospective chart review at the major provincial public
      hospital serving patients with spinal injuries/pathology. OBJECTIVES AND SETTING:
      To determine the incidence of spinal tuberculosis (Tb) and establish the profile
      of these patients treated at King George V Hospital (KGV) in KwaZulu-Natal, South
      Africa. METHODS: A total of 525 medical records for the period March 2005 to
      April 2006 were reviewed. Data from 104 files of Tb spine cases were categorized
      according to demographic details, medical conditions and length of stay in
      hospital. The South African mid-year 2006 census was used to calculate
      associations and risk rates for race, gender, adulthood, urbanization and
      employment and analyzed using the STATA version 9.0 statistical package. RESULTS:
      About 90% of the patients were African and 10% from other races. Females
      comprised 58% of the patients. The incidence of Tb spine is 1.02 per 100,000 and
      3.13 per 100,000 for Africans and other races, respectively. The incidence rate
      is 1.17 per 100,000 females and 0.916 per 100,000 males. All the participants had
      a history of pulmonary Tb and 28% were human immunodeficiency virus positive.
      Thoracic spine was affected in 42% of the cases. About 32% presented with
      incomplete paraplegia. The average length of stay at this hospital for these
      patients was 41 days. CONCLUSIONS: About 20% of all patients seen for spinal
      conditions at KGV over the past year presented with Tb spine. A higher
      association between living in an urban area, adulthood (age 18+), being non-Black
      patients and the occurrence of spinal Tb was observed.

PMID- 18317492
TI  - Is laparoscopic colectomy inferior to open colectomy for patients with curable
      colon cancer?

PMID- 18317493
TI  - Is reflux dyspareunia a real entity?

PMID- 18317494
TI  - Mechanisms of disease: the evolving understanding of liver allograft rejection.
AB  - Liver transplantation is a successful treatment for select forms of liver disease
      and is unrivalled amongst other forms of solid organ transplantation in the
      ability of the recipient to develop long-term tolerance to the allograft. Much of
      this success can be attributed to the inherently tolerogenic manner in which
      antigens are presented in the liver and the presence of specialized regulatory
      lymphocyte populations. These observations are not universal, however, and a
      proportion of recipients develop problematic allograft rejection. Anti-allograft
      responses lead to an influx of effector cells that target hepatic parenchymal
      cells and induce apoptosis through members of the tumor necrosis factor
      superfamily. Anti-rejection therapies have traditionally targeted the entire
      lymphocyte response against the allograft and, whilst these therapies have been
      efficacious at limiting effector cell responses, they have also had deleterious
      effects on the regulatory cell populations that are required to promote long-term
      tolerance. The emergence of newer anti-rejection drugs that have the potential to
      target the effector response selectively, whilst preserving the much needed
      tolerogenic responses, has afforded us the opportunity to refine our future
      immunosuppressant strategies.

PMID- 18317495
TI  - Should hypogonadal men who are suboptimally responsive to testosterone gel switch
      to another gel preparation?

PMID- 18317496
TI  - The evolution of midurethral slings.
AB  - Use of urethral slings in the treatment of incontinence started in the early 20th
      century. An evolution in understanding the pathogenesis of urinary incontinence
      led to development of the midurethral sling, which was designed to replace the
      natural suburethral vectors of support, as described in the integral theory.
      Since the introduction of tension-free vaginal tape in 1995, multiple other
      commercially available types of midurethral sling have been introduced. In
      general, these sling types share the common characteristics of using a thin, type
      I synthetic mesh inserted at a midurethral level and applied without tension. The
      midurethral sling procedure has subsequently undergone multiple technical
      modifications, predominantly alterations to the technique and route used for
      sling insertion. Despite the variety in techniques, available evidence suggests
      that all sling types provide efficacious and durable outcomes. Several adverse
      effects have been reported that are specific to certain techniques, and include
      the risk of vascular, enteric or nerve injury, lower urinary tract injury,
      urinary retention or voiding dysfunction, and vaginal erosion. Nonetheless, the
      midurethral sling provides a safe surgical option overall, and represents a
      notable advance in the treatment of stress urinary incontinence.

PMID- 18317497
TI  - How should PSA screening efforts be focused to prevent underdiagnosis and
      overdiagnosis of prostate cancer?

PMID- 18317498
TI  - Bactofection of lung epithelial cells in vitro and in vivo using a genetically
      modified Escherichia coli.
AB  - Bacteria-mediated gene transfer ('bactofection') has emerged as an alternative
      approach for genetic vaccination and gene therapy. Here, we assessed bactofection
      of airway epithelial cells in vitro and in vivo using an attenuated Escherichia
      coli genetically engineered to invade non-phagocytic cells. Invasive E. coli
      expressing green fluorescent protein (GFP) under the control of a prokaryotic
      promoter was efficiently taken up into the cytoplasm of cystic fibrosis tracheal
      epithelial (CFTE29o-) cells and led to dose-related reporter gene expression. In
      vivo experiments showed that following nasal instillation the vast majority of
      GFP-positive bacteria pooled in the alveoli. Further, bactofection was assessed
      in vivo. Mice receiving 5 x 10(8) E. coli carrying pCIKLux, in which luciferase
      (lux) expression is under control of the eukaryotic cytomegalovirus (CMV)
      promoter, showed a significant increase (P<0.01) in lux activity in lung
      homogenates compared to untransfected mice. Surprisingly, similar level of lux
      activity was observed for the non-invasive control strain indicating that the
      eukaryotic CMV promoter might be active in E. coli. Insertion of prokaryotic
      transcription termination sequences into pCIKLux significantly reduced
      prokaryotic expression from the CMV promoter allowing bactofection to be detected
      in vitro and in vivo. However, bacteria-mediated gene transfer leads to a
      significantly lower lux expression than cationic lipid GL67-mediated gene
      transfer. In conclusion, although proof-of-principle for lung bactofection has
      been demonstrated, levels were low and further modification to the bacterial
      vector, vector administration and the plasmids will be required.

PMID- 18317499
TI  - How SAFE is albumin for fluid resuscitation in critically ill patients with
      traumatic brain injury?

PMID- 18317500
TI  - A case of paraneoplastic myelopathy associated with the neuromyelitis optica
      antibody.
AB  - BACKGROUND: A 63-year-old woman with a history of metastatic breast cancer
      presented to the emergency department with chest pain in a band-like
      distribution. Within 1 day of presentation the patient developed bilateral lower
      extremity weakness and urinary retention. The emergence of these symptoms
      coincided with the recurrence of her metastatic breast cancer. Fifteen months
      before presentation the patient had experienced a similar episode of myelopathy
      in the setting of recurrence of her breast cancer, from which she recovered
      completely following treatment with steroids. INVESTIGATIONS: General and
      neurological examination, routine laboratory testing, MRI of the brain and spine,
      tests for serum autoimmune antibodies, infectious serology testing, lumbar
      puncture, paraneoplastic panel, neuromyelitis optica antibody testing, evaluation
      for celiac disease, CT scans of the chest, abdomen and pelvis, whole-body
      [(18)F]fluoro-2-deoxyglucose PET scan, lymph node biopsy, electroencephalography
      observing visual and brainstem auditory evoked potentials, and neuro
      ophthalmological examination. DIAGNOSIS: Myelopathy, possibly paraneoplastic,
      associated with the neuromyelitis optica antibody in the setting of metastatic
      breast cancer. MANAGEMENT: Corticosteroids to treat the myelopathy and
      chemotherapy for the breast cancer.

PMID- 18317501
TI  - A case of fluoxetine-induced syndrome of inappropriate antidiuretic hormone
      secretion.
AB  - BACKGROUND: A 58-year-old schizophrenic male who had been drinking at least 4-5 l
      of pure water every day for 30 years was admitted to a hospital with complaints
      of nausea, fatigue, and irregular, fluctuating fevers (up to 39 degrees C). He
      had previously been prescribed fluoxetine at a dose of 20 mg/day and had been
      using the drug for 28 days. INVESTIGATIONS: Review of medical history, physical
      examination, blood analysis, urine analysis, chest radiography and abdominal
      ultrasound. DIAGNOSIS: Psychogenic polydipsia and fluoxetine-induced syndrome of
      inappropriate antidiuretic hormone secretion. MANAGEMENT: Fluid restriction and
      discontinuation of fluoxetine.

PMID- 18317502
TI  - Renal artery embolization for the symptomatic treatment of adult polycystic
      kidney disease.

PMID- 18317503
TI  - C-reactive protein is neither a marker nor a mediator of atherosclerosis.

PMID- 18317504
TI  - MicroRNA target detection and analysis for genes related to breast cancer using
      MDLcompress.
AB  - We describe initial results of miRNA sequence analysis with the optimal symbol
      compression ratio (OSCR) algorithm and recast this grammar inference algorithm as
      an improved minimum description length (MDL) learning tool: MDLcompress. We apply
      this tool to explore the relationship between miRNAs, single nucleotide
      polymorphisms (SNPs), and breast cancer. Our new algorithm outperforms other
      grammar-based coding methods, such as DNA Sequitur, while retaining a two-part
      code that highlights biologically significant phrases. The deep recursion of
      MDLcompress, together with its explicit two-part coding, enables it to identify
      biologically meaningful sequence without needlessly restrictive priors. The
      ability to quantify cost in bits for phrases in the MDL model allows prediction
      of regions where SNPs may have the most impact on biological activity.
      MDLcompress improves on our previous algorithm in execution time through an
      innovative data structure, and in specificity of motif detection (compression)
      through improved heuristics. An MDLcompress analysis of 144 over expressed genes
      from the breast cancer cell line BT474 has identified novel motifs, including
      potential microRNA (miRNA) binding sites that are candidates for experimental
      validation.

PMID- 18317505
TI  - Common QTL affect the rate of tomato seed germination under different stress and
      nonstress conditions.
AB  - The purpose of this study was to determine whether the rates of tomato seed
      germination under different stress and nonstress conditions were under common
      genetic controls by examining quantitative trait loci (QTL) affecting such
      traits. Seeds of BC(1) progeny of a cross between a slow-germinating tomato
      breeding line and a rapid-germinating tomato wild accession were evaluated for
      germination under nonstress as well as cold, salt, and drought stress conditions.
      In each treatment, the most rapidly-germinating seeds were selected, grown to
      maturity, and subjected to molecular marker analysis. A selective genotyping
      approach detected between 6 and 9 QTL affecting germination rate under each of
      the four conditions, with a total of 14 QTL identified. Ten QTL affected
      germination rate under 2 or 3 conditions, which were considered germination
      related common QTL. Four QTL affected germination rate only in one treatment,
      which were considered germination-related, condition-specific QTL . The results
      indicated that mostly the same QTL affected seed germination under different
      stress and nonstress conditions, supporting a previous suggestion that similar
      physiological mechanisms contribute to rapid seed germination under different
      conditions. Marker-assisted selection for the common QTL may result in progeny
      with rapid seed germinability under different conditions.

PMID- 18317506
TI  - Diffusion maps clustering for magnetic resonance q-ball imaging segmentation.
AB  - White matter fiber clustering aims to get insight about anatomical structures in
      order to generate atlases, perform clear visualizations, and compute statistics
      across subjects, all important and current neuroimaging problems. In this work,
      we present a diffusion maps clustering method applied to diffusion MRI in order
      to segment complex white matter fiber bundles. It is well known that diffusion
      tensor imaging (DTI) is restricted in complex fiber regions with crossings and
      this is why recent high-angular resolution diffusion imaging (HARDI) such as Q
      Ball imaging (QBI) has been introduced to overcome these limitations. QBI
      reconstructs the diffusion orientation distribution function (ODF), a spherical
      function that has its maxima agreeing with the underlying fiber populations. In
      this paper, we use a spherical harmonic ODF representation as input to the
      diffusion maps clustering method. We first show the advantage of using diffusion
      maps clustering over classical methods such as N-Cuts and Laplacian eigenmaps. In
      particular, our ODF diffusion maps requires a smaller number of hypothesis from
      the input data, reduces the number of artifacts in the segmentation, and
      automatically exhibits the number of clusters segmenting the Q-Ball image by
      using an adaptive scale-space parameter. We also show that our ODF diffusion maps
      clustering can reproduce published results using the diffusion tensor (DT)
      clustering with N-Cuts on simple synthetic images without crossings. On more
      complex data with crossings, we show that our ODF-based method succeeds to
      separate fiber bundles and crossing regions whereas the DT-based methods generate
      artifacts and exhibit wrong number of clusters. Finally, we show results on a
      real-brain dataset where we segment well-known fiber bundles.

PMID- 18317507
TI  - Cone-beam composite-circling scan and exact image reconstruction for a quasi
      short object.
AB  - Here we propose a cone-beam composite-circling mode to solve the quasi-short
      object problem, which is to reconstruct a short portion of a long object from
      longitudinally truncated cone-beam data involving the short object. In contrast
      to the saddle curve cone-beam scanning, the proposed scanning mode requires that
      the X-ray focal spot undergoes a circular motion in a plane facing the short
      object, while the X-ray source is rotated in the gantry main plane. Because of
      the symmetry of the proposed mechanical rotations and the compatibility with the
      physiological conditions, this new mode has significant advantages over the
      saddle curve from perspectives of both engineering implementation and clinical
      applications. As a feasibility study, a backprojection filtration (BPF) algorithm
      is developed to reconstruct images from data collected along a composite-circling
      trajectory. The initial simulation results demonstrate the correctness of the
      proposed exact reconstruction method and the merits of the proposed mode.

PMID- 18317508
TI  - Structural and functional genomics of tomato.
AB  - Tomato (Solanum lycopersicum L.) is the most intensively investigated Solanaceous
      species both in genetic and genomics studies. It is a diploid species with a
      haploid set of 12 chromosomes and a small genome (950 Mb). Based on the detailed
      knowledge on tomato structural genomics, the sequencing of the euchromatic
      regions started in the year 2005 as a common effort of different countries. The
      manuscript focuses on markers used for tomato, on mapping efforts mainly based on
      exploitation of natural biodiversity, and it gives an updated report on the
      international sequencing activities. The principal tools developed to explore the
      function of tomato genes are also summarized, including mutagenesis, genetic
      transformation, and transcriptome analysis. The current progress in bioinformatic
      strategies available to manage the overwhelming amount of data generated from
      different tomato "omics" approaches is reported, and emphasis is given to the
      effort of producing a computational workbench for the analysis of the
      organization, as well as the functionality and evolution of the Solanaceae
      family.

PMID- 18317509
TI  - Radioiodine labeled anti-MIF McAb: a potential agent for inflammation imaging.
AB  - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that
      may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb
      can be used to detect in vivo inflammatory changes. The objective of this study
      was to investigate in vivo biology of radioiodinated anti-MIF McAb using the
      inflammation model mice. Anti-MIF McAb was radioiodinated with NaI125 by Iodogen
      method. Animal models were induced in the mice by intramuscular injection of S.
      aureus, E. coli, and turpentine oil. The biodistribution studies with
      radioiodinated anti-MIF McAb were performed on inflammation mice. The
      relationship between inflammatory lesions and anti-MIF McAb binding was
      investigated using the percent of injected dose per gram tissue (% ID/g) of
      tissue samples and whole-body autoradiography. The radioactivity of I125-anti-MIF
      McAb in the inflammatory tissue increased gradually for three inflammation
      models. The highest uptake was found in S. aureus group and the lowest was in E.
      coli group. The uptake in turpentine oil group was average. Whole-body
      autoradiography showed that all inflammation foci could be visualized clearly
      from 24 hours after injection, but 48 hours images were much clearer in
      accordance with the high T/NT ratio. These results demonstrate the ability of
      radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented
      by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants
      further investigation as a potential inflammation-seeking agent for imaging to
      detect inflammatory disorders.

PMID- 18317510
TI  - A full automatic device for sampling small solution volumes in photometric
      titration procedure based on multicommuted flow system.
AB  - In this work, an automatic device to deliver titrant solution into a titration
      chamber with the ability to determine the dispensed volume of solution, with good
      precision independent of both elapsed time and flow rate, is proposed. A glass
      tube maintained at the vertical position was employed as a container for the
      titrant solution. Electronic devices were coupled to the glass tube in order to
      control its filling with titrant solution, as well as the stepwise solution
      delivering into the titration chamber. The detection of the titration end point
      was performed employing a photometer designed using a green LED (lambda=545 nm)
      and a phototransistor. The titration flow system comprised three-way solenoid
      valves, which were assembled to allow that the steps comprising the solution
      container loading and the titration run were carried out automatically. The
      device for the solution volume determination was designed employing an infrared
      LED (lambda=930 nm) and a photodiode. When solution volume delivered from
      proposed device was within the range of 5 to 105 mul, a linear relationship (R =
      0.999) between the delivered volumes and the generated potential difference was
      achieved. The usefulness of the proposed device was proved performing photometric
      titration of hydrochloric acid solution with a standardized sodium hydroxide
      solution and using phenolphthalein as an external indicator. The achieved results
      presented relative standard deviation of 1.5%.

PMID- 18317511
TI  - Delays in referral of soft tissue sarcomas.
AB  - Introduction and aims. It is well established that soft tissue sarcomas (STSs)
      are more effectively treated in a specialist centre. However, delays in time
      taken for a patient to be referred to a specialist centre may lead to a poorer
      prognosis. This study aims to identify the length of these delays and where they
      occur. Patients and methods. Patients with a proven STS were included. They were
      recruited from both outpatient clinics and from the surgical ward of the Royal
      Orthopaedic Hospital (Birmingham, UK). A structured interview was used to take a
      detailed history of the patients' treatment pathway, before arriving at the
      specialist centre. Dates given were validated using the case notes. Results. The
      median time for the patient to present to a specialist centre from the onset of
      symptoms was 40.4 weeks. The median delay until presentation to a medical
      professional (patient delay) was 1.3 weeks. Median delay in referral to a
      specialist centre (service delay) was 25.0 weeks. Discussion. Medical
      professionals rather than patients contribute the greatest source of delay in
      patients reaching a specialist centre for treatment of STS. Adherence to
      previously published guidelines could decrease this delay for diagnosis of
      possible sarcoma. Steps should be taken to refer patients directly to a
      diagnostic centre if they have symptoms or signs suggestive of STS.

PMID- 18317512
TI  - Diabetic retinopathy in native and nonnative Canadians.
AB  - High prevalence rates of type 2 diabetes are being observed in native Canadian
      communities. It is believed that native populations have a higher prevalence rate
      of vascular complications than nonnatives. The Southern Alberta Study of Diabetic
      Retinopathy (DR) examined the prevalence and incidence of DR and associated
      metabolic abnormalities in native and nonnative subjects. Prevalence rates of DR
      in type 2 diabetic native and nonnative subjects were identical, with a
      prevalence rate of 40%. Native subjects with retinopathy, however, tended to have
      more advanced changes of retinopathy compared to the nonnative subjects. Key
      factors such as A1c, blood pressure, duration of diabetes, and lipid values were
      not significantly different between the two cohorts. These data indicate that
      ethnicity does play a role in the development and severity of DR but potential
      risk factors that may affect the development of retinopathy are not significantly
      different between native and nonnative groups.

PMID- 18317513
TI  - Peroxisome Proliferator-Activated Receptor-gamma Is a Potent Target for
      Prevention and Treatment in Human Prostate and Testicular Cancer.
AB  - Peroxisome proliferator-activated receptor-gamma (PPAR)-gamma is a ligand
      activated transcriptional factor belonging to steroid receptor superfamily. PPAR
      gamma plays a role in both adipocyte differentiation and tumorigenesis. Up to
      date, PPAR-gamma is expressed in various cancer tissues, and PPAR-gamma ligand
      induces growth arrest of these cancer cells. In this study, we examined the
      expression of PPAR-gamma in prostate cancer (PC) and testicular cancer (TC) by RT
      PCR and immunohistochemistry, and we also examined the effect of PPAR-gamma
      ligand in these cells by MTT assay, hoechest staining, and flow cytometry. PPAR
      gamma expression was significantly more extensive and intense in malignant
      tissues than in normal tissues. PPAR-gamma ligand induced the reduction of
      malignant cell viability through apoptosis. These results demonstrated that the
      generated PPAR-gamma in PC and TC cells might play an important role in the
      tumorigenesis. PPAR-gamma may become a new target in the treatment of PC and TC.

PMID- 18317514
TI  - Cryptochrome and Period Proteins Are Regulated by the CLOCK/BMAL1 Gene: Crosstalk
      between the PPARs/RXRalpha-Regulated and CLOCK/BMAL1-Regulated Systems.
AB  - Feeding and the circadian system regulate lipid absorption and metabolism, and
      the expression of enzymes involved in lipid metabolism is believed to be directly
      controlled by the clock system. To investigate the interaction between the lipid
      metabolism system and the circadian system, we analyzed the effect of a
      CLOCK/BMAL1 heterodimer on the transcriptional regulation of PPAR-controlled
      genes through PPAR response elements (PPREs). Transcription of acyl-CoA oxidase,
      cellular retinol binding protein II (CRBPII), and 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) synthase was altered by CLOCK/BMAL1, and transcriptional
      activity via PPRE by PPARs/RXRalpha was enhanced by CLOCK/BMAL1 and/or by PPARs
      ligand/activators. We also found that CLOCK/BMAL1-mediated transcription of
      period (PER) and cryptochrome (CRY) was modulated by PPARalpha/RXRalpha. These
      results suggest that there may be crosstalk between the PPARs/RXRalpha-regulated
      system and the CLOCK/BMAL1-regulated system.

PMID- 18317515
TI  - Clustering approach to quantify long-term spatio-temporal interactions in
      epileptic intracranial electroencephalography.
AB  - Abnormal dynamical coupling between brain structures is believed to be primarily
      responsible for the generation of epileptic seizures and their propagation. In
      this study, we attempt to identify the spatio-temporal interactions of an
      epileptic brain using a previously proposed nonlinear dependency measure. Using a
      clustering model, we determine the average spatial mappings in an epileptic brain
      at different stages of a complex partial seizure. Results involving 8 seizures
      from 2 epileptic patients suggest that there may be a fixed pattern associated
      with regional spatio-temporal dynamics during the interictal to pre-post-ictal
      transition.

PMID- 18317516
TI  - The Functions of PPARs in Aging and Longevity.
AB  - Peroxisome proliferator-activated receptors (PPARs) are key regulators in various
      age-associated pathophysiological processes related to energy metabolism and
      oxidative stress. A progressive rise of oxidative stress and related inflammatory
      reaction appears the hallmarks of the aging process and many age-related
      diseases. PPARs are important redox-sensitive transcription factors and their
      dyregulated activations seem to be major culprits for these pathological
      processes. Drugs targeting PPARs activity are already in widespread clinical use;
      however, based on these concepts, this review highlights the understanding of the
      role of PPARs in aging and indicates the necessary particular attention for the
      potential therapeutic uses of current PPAR agonists in age-associated diseases.

PMID- 18317517
TI  - Bioengineering of improved biomaterials coatings for extracorporeal circulation
      requires extended observation of blood-biomaterial interaction under flow.
AB  - Extended use of cardiopulmonary bypass (CPB) systems is often hampered by
      thrombus formation and infection. Part of these problems relates to imperfect
      hemocompatibility of the CPB circuitry. The engineering of biomaterial surfaces
      with genuine long-term hemocompatibility is essentially virgin territory in
      biomaterials science. For example, most experiments with the well-known Chandler
      loop model, for evaluation of blood-biomaterial interactions under flow, have
      been described for a maximum duration of 2 hours only. This study reports a
      systematic evaluation of two commercial CPB tubings, each with a hemocompatible
      coating, and one uncoated control. The experiments comprised (i) testing over 5
      hours under flow, with human whole blood from 4 different donors; (ii)
      measurement of essential blood parameters of hemocompatibility; (iii) analysis of
      the luminal surfaces by scanning electron microscopy and thrombin generation time
      measurements. The dataset indicated differences in hemocompatibility of the
      tubings. Furthermore, it appeared that discrimination between biomaterial
      coatings can be made only after several hours of blood-biomaterial contact.
      Platelet counting, myeloperoxidase quantification, and scanning electron
      microscopy proved to be the most useful methods. These findings are believed to
      be relevant with respect to the bioengineering of extracorporeal devices that
      should function in contact with blood for extended time.

PMID- 18317518
TI  - Clinical potential of quantum dots.
AB  - Advances in nanotechnology have led to the development of novel fluorescent
      probes called quantum dots. Quantum dots have revolutionalized the processes of
      tagging molecules within research settings and are improving sentinel lymph node
      mapping and identification in vivo studies. As the unique physical and chemical
      properties of these fluorescent probes are being unraveled, new potential methods
      of early cancer detection, rapid spread and therapeutic management, that is,
      photodynamic therapy are being explored. Encouraging results of optical and real
      time identification of sentinel lymph nodes and lymph flow using quantum dots in
      vivo models are emerging. Quantum dots have also superseded many of the
      limitations of organic fluorophores and are a promising alternative as a research
      tool. In this review, we examine the promising clinical potential of quantum
      dots, their hindrances for clinical use and the current progress in abrogating
      their inherent toxicity.

PMID- 18317519
TI  - Superparamagnetic iron oxide nanoparticles coated with galactose-carrying polymer
      for hepatocyte targeting.
AB  - Our goal is to develop the functionalized superparamagnetic iron oxide
      nanoparticles (SPIONs) demonstrating the capacities to be delivered in liver
      specifically and to be dispersed in physiological environment stably. For this
      purpose, SPIONs were coated with polyvinylbenzyl-O-beta-D-galactopyranosyl-D
      gluconamide (PVLA) having galactose moieties to be recognized by
      asialoglycoprotein receptors (ASGP-R) on hepatocytes. For use as a control, we
      also prepared SPIONs coordinated with 2-pyrrolidone. The sizes, size
      distribution, structure, and coating of the nanoparticles were characterized by
      transmission electron microscopy (TEM), electrophoretic light scattering
      spectrophotometer (ELS), X-ray diffractometer (XRD), and Fourier transform
      infrared (FT-IR), respectively. Intracellular uptake of the PVLA-coated SPIONs
      was visualized by confocal laser scanning microscopy, and their hepatocyte
      specific delivery was also investigated through magnetic resonance (MR) images of
      rat liver. MRI experimental results indicated that the PVLA-coated SPIONs possess
      the more specific accumulation property in liver compared with control, which
      suggests their potential utility as liver-targeting MRI contrast agent.

PMID- 18317520
TI  - Haptic stylus and empirical studies on braille, button, and texture display.
AB  - This paper presents a haptic stylus interface with a built-in compact tactile
      display module and an impact module as well as empirical studies on Braille,
      button, and texture display. We describe preliminary evaluations verifying the
      tactile display's performance indicating that it can satisfactorily represent
      Braille numbers for both the normal and the blind. In order to prove haptic
      feedback capability of the stylus, an experiment providing impact feedback
      mimicking the click of a button has been conducted. Since the developed device is
      small enough to be attached to a force feedback device, its applicability to
      combined force and tactile feedback display in a pen-held haptic device is also
      investigated. The handle of pen-held haptic interface was replaced by the pen
      like interface to add tactile feedback capability to the device. Since the system
      provides combination of force, tactile and impact feedback, three haptic
      representation methods for texture display have been compared on surface with 3
      texture groups which differ in direction, groove width, and shape. In addition,
      we evaluate its capacity to support touch screen operations by providing tactile
      sensations when a user rubs against an image displayed on a monitor.

PMID- 18317521
TI  - A suprachoroidal electrical retinal stimulator design for long-term animal
      experiments and in vivo assessment of its feasibility and biocompatibility in
      rabbits.
AB  - This article reports on a retinal stimulation system for long-term use in animal
      electrical stimulation experiments. The presented system consisted of an
      implantable stimulator which provided continuous electrical stimulation, and an
      external component which provided preset stimulation patterns and power to the
      implanted stimulator via a paired radio frequency (RF) coil. A rechargeable
      internal battery and a parameter memory component were introduced to the
      implanted retinal stimulator. As a result, the external component was not
      necessary during the stimulation mode. The inductive coil pair was used to pass
      the parameter data and to recharge the battery. A switch circuit was used to
      separate the stimulation mode from the battery recharging mode. The implantable
      stimulator was implemented with IC chips and the electronics, except for the
      stimulation electrodes, were hermetically packaged in a biocompatible metal case.
      A polyimide-based gold electrode array was used. Surgical implantation into
      rabbits was performed to verify the functionality and safety of this newly
      designed system. The electrodes were implanted in the suprachoroidal space.
      Evoked cortical potentials were recorded during electrical stimulation of the
      retina. Long-term follow-up using OCT showed no chorioretinal abnormality after
      implantation of the electrodes.

PMID- 18317522
TI  - Statistical analysis of twin populations using dissimilarity measurements in
      hippocampus shape space.
AB  - By analyzing interpoint comparisons, we obtain significant results describing the
      relationship in "hippocampus shape space" of clinically depressed, high-risk, and
      control populations. In particular, our analysis demonstrates that the high-risk
      population is closer in shape space to the control population than to the
      clinically depressed population.

PMID- 18317523
TI  - Proteome-level responses of Escherichia coli to long-chain fatty acids and use of
      fatty acid inducible promoter in protein production.
AB  - In Escherichia coli, a long-chain acyl-CoA is a regulatory signal that modulates
      gene expression through its binding to a transcription factor FadR. In this
      study, comparative proteomic analysis of E. coli in the presence of glucose and
      oleic acid was performed to understand cell physiology in response to oleic acid.
      Among total of 52 proteins showing altered expression levels with oleic acid
      presence, 9 proteins including AldA, Cdd, FadA, FadB, FadL, MalE, RbsB, Udp, and
      YccU were newly synthesized. Among the genes that were induced by oleic acid, the
      promoter of the aldA gene was used for the production of a green fluorescent
      protein (GFP). Analysis of fluorescence intensities and confocal microscopic
      images revealed that soluble GFP was highly expressed under the control of the
      aldA promoter. These results suggest that proteomics is playing an important role
      not only in biological research but also in various biotechnological
      applications.

PMID- 18317524
TI  - Formal implementation of a performance evaluation model for the face recognition
      system.
AB  - Due to usability features, practical applications, and its lack of intrusiveness,
      face recognition technology, based on information, derived from individuals'
      facial features, has been attracting considerable attention recently. Reported
      recognition rates of commercialized face recognition systems cannot be admitted
      as official recognition rates, as they are based on assumptions that are
      beneficial to the specific system and face database. Therefore, performance
      evaluation methods and tools are necessary to objectively measure the accuracy
      and performance of any face recognition system. In this paper, we propose and
      formalize a performance evaluation model for the biometric recognition system,
      implementing an evaluation tool for face recognition systems based on the
      proposed model. Furthermore, we performed evaluations objectively by providing
      guidelines for the design and implementation of a performance evaluation system,
      formalizing the performance test process.

PMID- 18317525
TI  - Mathematical modeling of cytotoxic lymphocyte-mediated immune response to
      hepatitis B virus infection.
AB  - Nowak's model of the human immunodeficiency virus (HIV) infection has been
      extensively and successfully used to simulate the interaction between HIV and
      cytotoxic lymphocyte- (CTL-) mediated immune response. However, this model is not
      available for hepatitis B virus (HBV) infection. As the enhanced recruitment of
      virus-specific CTLs into the liver has been an important novel concept in the
      pathogenesis of hepatitis B, we develop a specific mathematical model analyzing
      the relationship between HBV and the CTL-mediated immune response, and the
      indicator of the liver cell damage, alanine aminotransferase (ALT). The stability
      condition of the complete recovery equilibrium point at which HBV will be
      eliminated entirely from the body is discussed. A different set of parameters is
      used in the simulation, and the results show that the model can interpret the
      wide variety of clinical manifestations of HBV infection. The model suggests that
      a rapid and vigorous CTL response is required for resolution of HBV infection.

PMID- 18317526
TI  - An approximate numerical technique for characterizing optical pulse propagation
      in inhomogeneous biological tissue.
AB  - An approximate numerical technique for modeling optical pulse propagation through
      weakly scattering biological tissue is developed by solving the photon transport
      equation in biological tissue that includes varying refractive index and varying
      scattering/absorption coefficients. The proposed technique involves first tracing
      the ray paths defined by the refractive index profile of the medium by solving
      the eikonal equation using a Runge-Kutta integration algorithm. The photon
      transport equation is solved only along these ray paths, minimizing the overall
      computational burden of the resulting algorithm. The main advantage of the
      current algorithm is that it enables to discretise the pulse propagation space
      adaptively by taking optical depth into account. Therefore, computational
      efficiency can be increased without compromising the accuracy of the algorithm.

PMID- 18317527
TI  - Angioedema: clinical and etiological aspects.
AB  - Angioedema is an abrupt swelling of the skin, mucous membrane, or both including
      respiratory and gastrointestinal tracts. This study aimed to report an experience
      of angioedema in a university hospital with respect to etiologies, clinical
      features, treatment, and outcome. One hundred and five patients were enrolled.
      About half had angioedema without urticaria. The common sites of involvement were
      periorbital area and lips. Forty five patients (49%) had systemic symptoms. The
      most common cause of angioedema was allergic angioedema. Nonsteroidal anti
      inflammatory drug-induced angioedema and idiopathic angioedema were detected in
      20% and 18%, respectively. Among patients with allergic angioedema, 41.7% were
      caused by food, 39.6% by drugs. Thirty seven patients (39%) had recurrent attacks
      of angioedema. Mean standard deviation (SD) number of attacks in patients with
      recurrent angioedema was 3.9 (2.7) (ranging from 2 to 10 times). Patients who had
      older age and multiple sites of skin involvement had tendency to have systemic
      symptoms.

PMID- 18317528
TI  - CRALBP is a highly prevalent autoantigen for human autoimmune uveitis.
AB  - Cellular retinaldehyde binding protein (CRALBP) is an autoantigen in spontaneous
      equine recurrent uveitis. In order to test whether CRALBP contributes to human
      autoimmune uveitis, the specificity of antibodies from human uveitis patient's
      sera was first evaluated in two-dimensional (2D) Western blot analysis.
      Subsequent identification of the immunoreactive proteins by mass spectrometry
      resulted in the identification of CRALBP as a putative autoantigen. Additionally,
      sera from human uveitis and control patients were by Western blot using purified
      human recombinant CRALBP. Anti-CRALBP autoantibodies occur more frequently
      (P<.01) in human uveitis patients than in normal controls. Thirty out of 56
      tested uveitis patient's sera contained autoantibodies reactive against CRALBP,
      compared to only four out of 23 normal control subjects. The presence of CRALBP
      autoantibodies in 54% of tested uveitis patients supports CRALBP as a possible
      autoantigen in human autoimmune uveitis.

PMID- 18317529
TI  - Soluble triggering receptor expressed on myeloid cells 1 is released in patients
      with stable chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a
      systemic disease that is associated with increased serum levels of markers of
      systemic inflammation. The triggering receptor expressed on myeloid cells 1 (TREM
      1) is a recently identified activating receptor on neutrophils, monocytes, and
      macrophage subsets. TREM-1 expression is upregulated by microbial products such
      as the toll-like receptor ligand lipoteichoic acid of Gram-positive or
      lipopolysaccharides of Gram-negative bacteria. In the present study, sera from 12
      COPD patients (GOLD stages I-IV, FEV1 51 +/- 6%) and 10 healthy individuals were
      retrospectively analyzed for soluble TREM-1 (sTREM-1) using a newly developed
      ELISA. In healthy subjects, sTREM-1 levels were low (median 0.25 ng/mL, range 0
      5.9 ng/mL). In contrast, levels of sTREM-1 in sera of COPD patients were
      significantly increased (median 11.68 ng/mL, range 6.2-41.9 ng/mL, P<.05).
      Furthermore, serum levels of sTREM-1 showed a significant negative correlation
      with lung function impairment. In summary, serum concentrations of sTREM-1 are
      increased in patients with COPD. Prospective studies are warranted to evaluate
      the relevance of sTREM-1 as a potential marker of the disease in patients with
      COPD.

PMID- 18317530
TI  - The possible correlation between the patient's immune tolerance level during
      cesaerean section and the incidence of subsequent emergency peripartum
      hysterectomy.
AB  - INTRODUCTION: Cesarean section is an independent risk factor for peripartum
      hysterectomy. As a method of delivery, cesarean section may interfere with a
      number of molecular changes that occur at the maternal-fetal interface during the
      course of labor. METHODS: The level of CD3, CD56, CD25, and CD69 antigen
      immunoreactivity was assessed by immunohistochemistry in 26 decidual tissue
      samples. The tissue samples were obtained from 18 women who underwent cesarean
      sections at term and from 8 women who underwent cesarean hysterectomies. RESULTS:
      An increase in the activity and infiltration of immune cells in the decidua
      sampled during the spontaneous beginning of labor was observed. The further
      progression of labor was accompanied by a decrease in the number and activity of
      immune cells. The number of CD56+ and CD3+ cells in the decidua was statistically
      significantly lower in patients who had undergone cesarean hysterectomies than in
      those who had had cesarean sections at term. CONCLUSION: Abnormal immune response
      during labor may increase the risk for peripartum hysterectomy.

PMID- 18317531
TI  - Pro- and anti-inflammatory cytokine balance in major depression: effect of
      sertraline therapy.
AB  - The specific associations between antidepressant treatment and alterations in the
      levels of cytokines remain to be elucidated. In this study, we aimed to explore
      the role of IL-2, IL-4, IL-12, TNF-alpha, TGF-beta1, and MCP-1 in major
      depression and to investigate the effects of sertraline therapy. Cytokine and
      chemokine levels were measured at the time of admission and 8 weeks after
      sertraline treatment. Our results suggest that the proinflammatory cytokines (IL
      2, IL-12, and TNF-alpha) and MCP-1 were significantly higher, whereas anti
      inflammatory cytokines IL-4 and TGF-beta1 were significantly lower in patients
      with major depression than those of healthy controls. It seems likely that the
      sertraline therapy might have exerted immunomodulatory effects through a decrease
      in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory
      cytokines IL-4 and TGF-beta1. In conclusion, our results indicate that Th1-, Th2
      , and Th3-type cytokines are altered in the depressed patients and some of them
      might have been corrected by sertraline treatment.

PMID- 18317532
TI  - Blurring borders: innate immunity with adaptive features.
AB  - Adaptive immunity has often been considered the penultimate of immune capacities.
      That system is now being deconstructed to encompass less stringent rules that
      govern its initiation, actual effector activity, and ambivalent results.
      Expanding the repertoire of innate immunity found in all invertebrates has
      greatly facilitated the relaxation of convictions concerning what actually
      constitutes innate and adaptive immunity. Two animal models, incidentally not on
      the line of chordate evolution (C. elegans and Drosophila), have contributed
      enormously to defining homology. The characteristics of specificity and memory
      and whether the antigen is pathogenic or nonpathogenic reveal considerable
      information on homology, thus deconstructing the more fundamentalist view.
      Senescence, cancer, and immunosuppression often associated with mammals that
      possess both innate and adaptive immunity also exist in invertebrates that only
      possess innate immunity. Strict definitions become blurred casting skepticism on
      the utility of creating rigid definitions of what innate and adaptive immunity
      are without considering overlaps.

PMID- 18317533
TI  - IPEX as a result of mutations in FOXP3.
AB  - Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is
      a rare disorder caused by mutations in the FOXP3 gene that result in the
      defective development of CD4+CD25+ regulatory T cells which constitute an
      important T cell subset involved in immune homeostasis and protection against
      autoimmunity. Their deficiency is the hallmark of IPEX and leads to severe
      autoimmune phenomena including autoimmune enteropathy, dermatitis, thyroiditis,
      and type 1 diabetes, frequently resulting in death within the first 2 years of
      life. Apart from its clinical implications, IPEX illustrates the importance of
      immunoregulatory cells such as CD4+CD25+ regulatory T cells.

PMID- 18317535
TI  - Attenuated disease in SIV-infected macaques treated with a monoclonal antibody
      against FasL.
AB  - Acute SIVmac infection in macaques is accompanied by high levels of plasma
      viremia that decline with the appearance of viral immunity and is a model for
      acute HIV disease in man. Despite specific immune responses, the virus
      establishes a chronic, persistent infection. The destruction of CD4+ and CD4-
      lymphocyte subsets in macaques contributes to viral persistence and suggests the
      importance of mechanisms for depleting both infected and uninfected (bystander)
      cells. Bystander cell killing can occur when FasL binds the Fas receptor on
      activated lymphocytes, which include T and B cell subpopulations that are
      responding to the infection. Destruction of specific immune cells could be an
      important mechanism for blunting viral immunity and establishing persistent
      infection with chronic disease. We inhibited the Fas pathway in vivo with a
      monoclonal antibody against FasL (RNOK203). Here we show that treatment with anti
      FasL reduced cell death in circulating T and B cells, increased CTL and antibody
      responses to viral proteins, and lowered the setpoint viremia. By blocking FasL
      during only the first few weeks after infection, we attenuated SIVmac disease and
      increased the life span for infected and treated macaques.

PMID- 18317536
TI  - Ambulance diagnosis of ST elevation myocardial infarction eligible for primary
      PCI.

PMID- 18317534
TI  - Regulatory T cells and human disease.
AB  - The main function of our immune system is to protect us from invading pathogens
      and microorganisms by destroying infected cells, while minimizing collateral
      damage to tissues. In order to maintain this balance between immunity and
      tolerance, current understanding of the immune system attributes a major role to
      regulatory T cells (Tregs) in controlling both immunity and tolerance. Various
      subsets of Tregs have been identified based on their expression of cell surface
      markers, production of cytokines, and mechanisms of action. In brief, naturally
      occurring thymic-derived CD4+CD25+ Tregs are characterized by constitutive
      expression of the transcription factor FOXP3, while antigen-induced or adaptive
      Tregs are mainly identified by expression of immunosuppressive cytokines
      (interleukin-10 (IL-10) and/or transforming growth factor-beta (TGF-beta)). While
      Tregs in normal conditions regulate ongoing immune responses and prevent
      autoimmunity, imbalanced function or number of these Tregs, either enhanced or
      decreased, might lead, respectively, to decreased immunity (e.g., with tumor
      development or infections) or autoimmunity (e.g., multiple sclerosis). This
      review will discuss recent research towards a better understanding of the biology
      of Tregs, their interaction with other immune effector cells, such as dendritic
      cells, and possible interventions in human disease.

PMID- 18317537
TI  - Prehospital diagnosis in STEMI patients treated by primary PCI: the key to rapid
      reperfusion.
AB  - BACKGROUND: Primary coronary intervention (PCI) for acute myocardial infarction
      should be performed as quickly as possible, with a door-toballoon time of less
      then 90 minutes. However, in daily practice this cannot always be achieved.
      Prehospital diagnosis of ST-elevation myocardial infarction (STEMI) is of major
      importance in reducing time to treatment, in particular when patients can be
      transported directly to a centre with interventional capacities. OBJECTIVES: The
      aim of the current study was to evaluate the time from prehospital diagnosis of
      STEMI to balloon inflation and identify factors related to treatment delay in
      patients directly referred to the catheterisation laboratory of the University
      Medical Centre of Groningen. METHODS: A cross-sectional descriptive design was
      used to collect data on patients treated with primary PCI after prehospital
      diagnosis of STEMI. RESULTS: Median prehospital diagnosis-to-balloon time was 64
      minutes for patients directly admitted to the catheterisation laboratory and 75
      minutes for patients initially admitted to the coronary care unit. A delay longer
      than 90 minutes was observed in 18 patients. Higher age was associated with
      longer delay times (p=0.041). Long delays were not associated with diabetes
      (p=0.293), time from symptom onset to prehospital diagnosis (p=0.87) or time of
      day (p=0.09). Initial unavailability of the catheterisation laboratory due to
      running procedures contributed to longer delay times in ten cases. CONCLUSION:
      Prehospital diagnosis of STEMI and direct referral to a catheterisation
      laboratory for primary PCI allows a prehospital diagnosis-toballoon time of less
      than 90 minutes in 82% of patients. Older patients are at risk of longer delays.
      (Neth Heart J 2008;16:5-9.).

PMID- 18317538
TI  - Mechanisms involved in symptomatic myocardial bridging: Value of sequential
      testing for endothelial function, flow reserve measurements and dobutamine stress
      angiography.
AB  - BACKGROUND: In patients with extensive myocardial bridging, evaluation of its
      clinical significance remains a challenge. HYPOTHESIS: Sequential invasive
      testing is feasible and gives more insight into the pathophysiological mechanism
      of bridging-related angina. METHODS: Twelve patients with chest pain, proven
      ischaemia and extensive myocardial bridging were assessed. Myocardial bridging
      was evaluated at rest, during intracoronary acetylcholine infusion, through
      coronary flow velocity and flow reserve measurements, and during dobutamine
      stress. RESULTS: The mean length of the bridging segment was 24.9 mm (QCA; range
      8.4-48.0 mm). Acetylcholine infusion caused severe vasospasm in two patients. In
      these two patients anginal symptoms were related to vasospasm and sequential
      testing was discontinued. In the remaining ten patients sequential testing was
      continued. Coronary flow reserve was normal in all patients: 3.3+/-0.6. In six
      patients reliable quantitative measurements could be performed during dobutamine
      stress. The mean systolic diameter of the bridging segment was 1.6+/-0.4 at
      baseline and 1.3+/-0.3 during dobutamine stress (mean of differences 0.38 (95% CI
      0.1-0.7)). The difference between the diastolic and systolic diameter in the
      bridging segment increased from 0.3+/-0.2 mm at baseline to 1.0+/-0.5 mm during
      dobutamine infusion (mean of differences 0.6 (95% CI 0.3 to 0.9)). CONCLUSION:
      Sequential testing for bridging is feasible and may disclose endothelial
      dysfunction or spasm as an underlying mechanism in a minority of patients.
      Coronary flow reserve was preserved. Dobutamine stress unmasked further lumen
      reduction and may give further insight into the clinical significance of
      myocardial bridging in individual patients. (Neth Heart J 2008;16:10-5.).

PMID- 18317539
TI  - History of echocardiography in the Netherlands: 30 years of education and
      clinical applications.
AB  - The development of ultrasound has created great opportunities for diagnostic
      cardiac imaging. For more than 30 years, echocardiography has been the most
      important and cost-effective diagnostic imaging modality in clinical cardiology.
      Many developments originated in the Netherlands, including the very first
      practical real-time crosssectional imaging of the moving heart with a linear
      array. Milestones include the first portable echo apparatus, early versions of
      echo catheters and transoesophageal echocardiography probes as well as many
      clinical 'firsts' with reference to the more than 100 Dutch dissertations related
      to echocardiography. The future of echocardiography promises to be as productive
      and exciting as it has been in the previous three decades, including
      threedimensional echocardiography, myocardial perfusion echocardiography, tissue
      Doppler imaging and speckle tracking. New potential therapeutic applications are
      upcoming. In this article, the advances of echocardiography in the Netherlands
      are described, in the past and during 30 years of education, as was recently
      presented by three Dutch pioneers during the 'Echomiddagen 2006-2007' organised
      by the CVOI. (Neth Heart J 2008;16:16-20.).

PMID- 18317540
TI  - Rapid oral desensitisation procedure in clopidogrel hypersensitivity.
AB  - We describe a patient who developed generalised pruritus with oedema and rash two
      weeks after she had started taking clopidogrel following coronary stent
      implantation. In the absence of other likely causative agents, clopidogrel
      hypersensitivity was probable. She was treated with a rapid oral desensitisation
      procedure, after which a daily dose of 75 mg clopidogrel was well tolerated. No
      major adverse events occurred during a follow-up period of eight months. Oral
      desensitisation in clopidogrel hypersensitivity seems to be a safe method to
      reduce the risk of coronary stent thrombosis. (Neth Heart J 2008;16:21-3.).

PMID- 18317541
TI  - Thrombus in a normal left ventricle.

PMID- 18317542
TI  - Ayurveda is Embraced by eCAM.

PMID- 18317544
TI  - The life threatened child and the life enhancing clown: towards a model of
      therapeutic clowning.
AB  - In the last decade, there has been a rapid growth in the presence of clowns in
      hospitals, particularly in pediatric settings. The proliferation of clowns in
      health care settings has resulted in varying levels of professionalism and
      accountability. For this reason, there is a need to examine various forms of
      clowning, in particular therapeutic clowning in pediatric settings. The purpose
      of this article is to address what therapeutic clowning is and to describe the
      extent to which it can provide a complementary form of health care. In an attempt
      to apply theory to practice, the article will draw upon the experiences of a
      therapeutic clown within a pediatric setting while providing a historical and
      theoretical account of how clowns came to be in hospitals. Toward this end, a
      proposed model of therapeutic clowning will be offered which can be adapted for a
      variety of settings where children require specialized forms of play in order to
      enhance their coping, development and adjustment to life changes. Finally,
      current research on clowning in children's hospitals will be reviewed including a
      summary of findings from surveys administered at the Hospital for Sick Children.

PMID- 18317543
TI  - The Medicinal Mushroom Agaricus blazei Murrill: Review of Literature and Pharmaco
      Toxicological Problems.
AB  - Agaricus blazei Murrill (ABM) popularly known as 'Cogumelo do Sol' in Brazil, or
      'Himematsutake' in Japan, is a mushroom native to Brazil, and widely cultivated
      in Japan for its medicinal uses, so it is now considered as one of the most
      important edible and culinary-medicinal biotechnological species. It was
      traditionally used to treat many common diseases like atherosclerosis, hepatitis,
      hyperlipidemia, diabetes, dermatitis and cancer. In vitro and in vivo ABM has
      shown immunomodulatory and antimutagenic properties, although the biological
      pathways and chemical substances involved in its pharmacological activities are
      still not clear. The polysaccharides phytocomplex is thought to be responsible
      for its immunostimulant and antitumor properties, probably through an opsonizing
      biochemical pathway. Clinical studies are positive confirmations, but we are
      still at the beginning, and there are perplexing concerns especially relative to
      the content of agaritine. Argantine is a well-known carcinogenic and toxic
      substance in animals, that must be completely and fully evaluated.

PMID- 18317545
TI  - The treatment of pulmonary diseases and respiratory-related conditions with
      inhaled (nebulized or aerosolized) glutathione.
AB  - Reduced glutathione or simply glutathione (gamma-glutamylcysteinylglycine; GSH)
      is found in the cytosol of most cells of the body. GSH in the epithelial lining
      fluid (ELF) of the lower respiratory tract is thought to be the first line of
      defense against oxidative stress. Inhalation (nebulized or aerosolized) is the
      only known method that increases GSH's levels in the ELF. A review of the
      literature was conducted to examine the clinical effectiveness of inhaled GSH as
      a treatment for various pulmonary diseases and respiratory-related conditions.
      This report also discusses clinical and theoretical indications for GSH
      inhalation, potential concerns with this treatment, its presumed mechanisms of
      action, optimal doses to be administered and other important details. Reasons for
      inhaled GSH's effectiveness include its role as a potent antioxidant, and
      possibly improved oxygenation and host defenses. Theoretical uses of this
      treatment include Farmer's lung, pre- and postexercise, multiple chemical
      sensitivity disorder and cigarette smoking. GSH inhalation should not be used as
      a treatment for primary lung cancer. Testing for sulfites in the urine is
      recommended prior to GSH inhalation. Minor side effects such as transient
      coughing and an unpleasant odor are common with this treatment. Major side
      effects such as bronchoconstriction have only occurred among asthma patients
      presumed to be sulfite-sensitive. The potential applications of inhaled GSH are
      numerous when one considers just how many pulmonary diseases and respiratory
      related conditions are affected by deficient antioxidant status or an over
      production of oxidants, poor oxygenation and/or impaired host defenses. More
      studies are clearly warranted.

PMID- 18317546
TI  - Humor and Laughter May Influence Health: III. Laughter and Health Outcomes.
AB  - This is part three of a four-part series reviewing the evidence on how humor
      influences physiological and psychological well-being. The first article included
      basic background information, definitions and a review of the theoretical
      underpinnings for this area of research. The second article discussed use of
      humor as a complementary therapy within various clinical samples, as well as
      evidence concerning how a sense of humor influences physiological and
      psychological wellbeing. This third article examines how laughter influences
      health outcomes; including muscle tension, cardio-respiratory functioning and
      various stress physiology measures.

PMID- 18317547
TI  - Mind/Body psychological treatments for irritable bowel syndrome.
AB  - Currently, the goal of treatment for those with irritable bowel syndrome (IBS) is
      to improve the quality of life through a reduction in symptoms. While the
      majority of treatment approaches involve the use of traditional medicine, more
      and more patients seek out a non-drug approach to managing their symptoms.
      Current forms of non-drug psychologic or mind/body treatment for IBS include
      hypnotherapy, cognitive behavioral therapy and brief psychodynamic psychotherapy,
      all of which have been proven efficacious in clinical trials. We propose that
      incorporating the constructs of mindfulness and acceptance into a mind/body
      psychologic treatment of IBS may be of added benefit due to the focus on changing
      awareness and acceptance of one's own state which is a strong component of
      traditional and Eastern healing philosophies.

PMID- 18317548
TI  - First International Conference between West and East-Leonardo and Lao-Tze.
      Western Science Meets Eastern Wisdom. Experiences of Scientists and Intellectuals
      for the Creation of a New Paradigm of Modern Science.
AB  - The Conference was organized and supported by: Nei Dan School (European School of
      Internal Martial Arts), NIB (Laboratory of Molecular Biology and Stem Cell
      Bioengineering, National Institute of Biostructures and Biosystems, Institute of
      Cardiology, S.Orsola-Malpighi Hospital, Bologna), WACIMA (Worldwide Association
      Chinese Internal Martial Arts), Arti D'Oriente(Magazine of Eastern culture and
      traditions), Nuovo Orizzonte (Taiji Quan School in Florence), Samurai (Journal on
      Martial Arts), and Pinus (First National Institute for the Unification of Medical
      Strategies). Nei Dan School (www.taichineidan.com, neidan@libero.it) was in
      charge of the organization. Future meetings of the Centro studi 'Tao and Science'
      will take place in spring 2007 in Firenze and in October 2007 in Bologna. For
      information: E-mail: neidan@libero.it; web site: www.taichineidan.com,
      www.taoandscience.com.

PMID- 18317549
TI  - Inhibitory Response of Raphanus sativus on Lipid Peroxidation in Albino Rats.
AB  - In the present study, inhibitory effect of the methanol extract of Raphanus
      sativus root on lipid peroxidation has been carried out in normal rats. Graded
      doses of methanol extract of root of the plant (40, 80 and 120 mg kg(-1) body
      weight) were administered orally for 15 days to experimental treated rats.
      Distilled water was administered to experimental control rats. At the end of
      experiment, rats were killed by decapitation after ether anesthesia. Blood and
      liver were collected to measure thiobarbituric acid reactive substance, reduced
      glutathione and activity of catalase. Results indicated that the extract of R.
      sativus root reduced the levels of thiobarbituric acid reactive substance
      significantly in all experimental treated groups (P < 0.05) as compared to the
      experimental control group. It also increased the levels of reduced glutathione
      and increased the activity of catalase. In vitro experiments with the liver of
      experimental control and experimental treated rats were also carried out against
      cumene hydroperoxide induced lipid peroxidation. The extract inhibited in vitro
      cumene hydroperoxide induced lipid peroxidation. R. sativus inhibits lipid
      peroxidation in vivo and in vitro. It provides protection by strengthening the
      antioxidants like glutathione and catalase. Inclusion of this plant in every day
      diet would be beneficial.

PMID- 18317550
TI  - Oral Bromelain Attenuates Inflammation in an Ovalbumin-induced Murine Model of
      Asthma.
AB  - Bromelain, a widely used pineapple extract with cysteine protease activity, has
      been shown to have immunomodulatory effects in a variety of immune system models.
      The purpose of the present study was to determine the effects of orally
      administered bromelain in an ovalbumin (OVA)-induced murine model of acute
      allergic airway disease (AAD). To establish AAD, female C57BL/6J mice were
      sensitized with intraperitoneal (i.p.) OVA/alum and then challenged with OVA
      aerosols for 3 days. Mice were gavaged with either (phosphate buffered saline)PBS
      or 200 mg/kg bromelain in PBS, twice daily for four consecutive days, beginning 1
      day prior to OVA aerosol challenge. Airway reactivity and methacholine
      sensitivity, bronchoalveolar lavage (BAL) cellular differential, Th2 cytokines IL
      5 and IL-13, and lung histology were compared between treatment groups. Oral
      bromelain-treatment of AAD mice demonstrated therapeutic efficacy as evidenced by
      decreased methacholine sensitivity (P </= 0.01), reduction in BAL eosinophils (P
      </= 0.02) and IL-13 concentrations (P </= 0.04) as compared with PBS controls. In
      addition, oral bromelain significantly reduced BAL CD19+ B cells (P </= 0.0001)
      and CD8+ T cells (P </= 0.0001) in AAD mice when compared with controls. These
      results suggest that oral treatment with bromelain had a beneficial therapeutic
      effect in this murine model of asthma and bromelain may also be effective in
      human conditions.

PMID- 18317551
TI  - Green brazilian propolis action on macrophages and lymphoid organs of chronically
      stressed mice.
AB  - Stress is a generic term that summarizes how psychosocial and environmental
      factors influence physical and mental well-being. The interaction between stress
      and immunity has been widely investigated, involving the neuroendocrine system
      and several organs. Assays using natural products in stress models deserve
      further investigation. Propolis immunomodulatory action has been mentioned and it
      has been the subject of scientific investigation in our laboratory. The aim of
      this study was to evaluate if and how propolis activated macrophages in BALB/c
      mice submitted to immobilization stress, as well as the histopathological
      analysis of the thymus, bone marrow, spleen and adrenal glands. Stressed mice
      showed a higher hydrogen peroxide (H(2)O(2)) generation by peritoneal
      macrophages, and propolis treatment potentiated H(2)O(2) generation and inhibited
      nitric oxide (NO) production by these cells. Histopathological analysis showed no
      alterations in the thymus, bone marrow and adrenal glands, but increased germinal
      centers in the spleen. Propolis treatment counteracted the alterations found in
      the spleen of stressed mice. New research is being carried out in order to
      elucidate propolis immunomodulatory action during stress.

PMID- 18317552
TI  - Amelioration of heat stress induced disturbances of antioxidant defense system in
      chicken by brahma rasayana.
AB  - Since the range of comfort zone or thermo neutral zone of domestic chickens is
      narrow, they become easily susceptible to heat and cold environmental stress. We
      evaluated Brahma Rasayana (BR) supplementation on concentrations of certain
      oxidative stress markers associated with heat stress. A total of 48 egg type male
      chickens of local strain were divided into six groups (n = 8) for the study.
      Three groups were fed with BR orally at the rate of 2 g/kg bw daily for 10 days
      prior to and during the period of experiment. Two of the four groups that were
      exposed to heat stress (HST i.e. to a temperature of 40 +/- 1 degrees C and
      relative humidity of 80 +/- 5% in an environmental chamber) for 4 h daily for 5
      or 10 days, received BR orally. The other two groups remained as BR treated and
      untreated non-heat stressed (NHST) controls. There was a significant (P < 0.05)
      increase in the activities of antioxidant enzymes in blood such as catalase (CAT)
      and superoxide dismutase (SOD), as well as liver CAT, glutathione peroxidase
      (GPX) and glutathione reductase (GR) in NHST-BR treated and HST-BR treated (both
      5 and 10 days) chickens when compared with untreated controls. A great deal of
      significant (P < 0.05) variations were seen in serum and liver reduced
      glutathione (GSH) concentration in NHST-BR treated and HST-BR treated (both 5 and
      10 days) chickens. Serum and liver lipid peroxidation levels were found to be
      significantly (P < 0.05) higher in HST-untreated (both 5 and 10 days) chickens
      when compared with other groups. Thus BR supplementation during HST brings about
      enhanced action of enzymatic and non-enzymatic antioxidants, which nullified the
      undesired side effects of free radicals that are generated during HST.

PMID- 18317553
TI  - Phellinus linteus Extract Augments the Immune Response in Mitomycin C-Induced
      Immunodeficient Mice.
AB  - Phellinus linteus is a fungus distributed throughout Japan, Korea and China.
      Boiled water-soluble extracts from P. linteus (PLW) have shown anti-tumor and
      immunomodulatory properties in experiments done by intraperitoneal treatment, or
      in in vitro cell cultures. This is the first investigation on how oral
      administration of PLW influences immune responses. Here, we established
      immunodeficient mice by mitomycin C (MMC) and then researched how PLW influenced
      plaque-forming cell (PFC) production and populations of cytokine [interferon-
      (IFNgamma-) and interleukin-4 (IL-4)]-producing T lymphocytes. PLW samples were
      administered orally for 19 days (1, 2 or 4 g/kg/day). PFC assay was followed
      using Jerne's method. IFN- and IL-4-producing T lymphocyte populations were
      measured by flow-activated cell sorter (FACS). These assays were conducted the
      day after the last oral administration. MMC groups were given MMC (1 mg/kg/day)
      intraperitoneally for 6 days with PLW administration. The number of PFC per 10(6)
      spleen cells increased significantly in the PLW (2 g/kg/day) group when compared
      with the MMC-control (P < 0.05) while populations of IFNgamma- and IL-4-producing
      T lymphocytes decreased by MMC treatment. However, the PLW group tended to
      increase more than the MMC-control. Our results indicated that PLW augments the
      immune response of the spleen in MMC-induced immunodeficient mice.

PMID- 18317554
TI  - Post-Coital Antifertility Activity of Hibiscus rosa-sinensis Linn. roots.
AB  - Ancient literature mentions the use of a number of plants/preparations for
      fertility regulation. Some local contraceptive agents have also been described in
      Ayurvedic and Unani texts. Documented experiments or clinical data are, however,
      lacking. Therefore, the present study was undertaken to explore the antifertility
      and estrogenic activity of ethanolic extract of the roots of Hibiscus rosa
      sinensis Linn. A strong anti-implantation (inhibition 100%) and uterotropic
      activity was observed at the dose level of 400 mg/kg body weight. Histological
      studies were carried out to confirm this effect.

PMID- 18317555
TI  - Evaluation of Antioxidant and Wound Healing Effects of Alcoholic and Aqueous
      Extract of Ocimum sanctum Linn in Rats.
AB  - In recent years, oxidative stress and free radicals have been implicated in
      impaired wound healing. Ocimum sanctum (O. sanctum), a plant widely used in
      Ayurveda, possesses anti-inflammatory and antioxidant properties. The present
      study was undertaken to assess the potential of alcoholic and aqueous extracts in
      wound healing in Wistar albino rats. The rats were divided into five groups of
      six animals each. Group 1 is normal wounded control and the other four groups
      were treated with two different doses each of alcoholic and aqueous extract of O.
      sanctum. The wound healing parameters were evaluated by using incision, excision
      and dead space wounds in extract-treated rats and controls. Both the doses of
      alcoholic and aqueous extract significantly increased wound breaking strength,
      hydroxyproline, hexuronic acid, hexosamines, superoxide dismutase, catalase,
      reduced glutathione and significantly decreased percentage of wound contraction
      and lipid peroxidation when compared with the control group. The results suggest
      that O. sanctum has antioxidant properties, which may be responsible and
      favorable for faster wound healing and this plant extract may be useful in the
      management of abnormal healing and hypertropic scars.

PMID- 18317556
TI  - Single-blind and Double-blind Randomized Controlled Trials of Palmtherapy(R), an
      Alternative Medical Approach, for Anxiety before Cardiac Catheterization.
AB  - Alternative medicine is widely used, but lacks consensus regarding its
      amenability to scientific investigation. Anxiety increases morbidity and
      mortality in ischemic heart disease. We performed two studies of Palmtherapy(R),
      an alternative treatment, for anxiety before cardiac catheterization. In the
      first study, patients were randomized to receive pressure at particular points on
      the palm, or at incorrect locations, for about 50 min, while the therapist
      conversed with them. In the second study, the conversation was conducted by a
      second, 'blind' investigator. In both studies, patients and nurses, all blind to
      treatment assignment, completed visual analog scale and National Institute of
      Mental Health measures of anxiety, respectively. Twenty-three subjects completed
      study 1, and 17 completed study 2. In study 1, palm therapy was superior to sham
      therapy for both outcome measures. In study 2, palm therapy was superior for self
      reported anxiety, but not for nurses' assessments of anxiety. Future studies
      should attempt to separate possible mechanistic effects of Palmtherapy(R) from
      therapist-related variables. Whether alternative medicine deserves to be studied
      at all remains controversial. Palmtherapy(R) may offer anxiolytic benefit without
      the harm attributable to drugs.

PMID- 18317557
TI  - Exploring of Antimicrobial Activity of Triphala Mashi-an Ayurvedic Formulation.
AB  - Triphala Mashi is an ayurvedic formulation that was prepared in our lab. Aqueous
      and alcoholic extracts of both Triphala and Triphala Mashi were used, to evaluate
      antimicrobial activity. Comparative phytochemical profile of Triphala and
      Triphala Mashi was done by preliminary phytochemical screening, total phenolic
      content and thin layer chromatography (TLC). Antimicrobial activity includes
      isolation of pathogens from clinical samples, its characterization, testing its
      multiple drug resistance against standard antibiotics and antimicrobial activity
      of aqueous and alcoholic extracts of both Triphala and Triphala Mashi against
      these organisms by using agar gel diffusion method. Triphala Mashi containing
      phenolic compounds, tannins exhibited comparable antimicrobial activity in
      relation to Triphala against all the microorganisms tested. It inhibits the dose
      dependent growth of Gram-positive and Gram-negative bacteria. In conclusion, it
      appears that Triphala Mashi has non-specific antimicrobial activity.

PMID- 18317559
TI  - Providing supportive care to cancer patients: a study on inter-organizational
      relationships.
AB  - BACKGROUND: Supportive cancer care (SCC) has historically been provided by
      organizations that work independently and possess limited inter-organizational
      coordination. Despite the recognition that SCC services must be better
      coordinated, little research has been done to examine inter-organizational
      relationships that would enable this goal. OBJECTIVE: The purpose of this study
      was to describe relationships among programs that support those affected by
      cancer. Through this description the study objective was to identify the optimal
      approach to coordinating SCC in the community. METHODS: Senior administrators in
      programs that provided care to persons and their families living with or affected
      by cancer participated in a personal interview. SETTING: South-central Ontario,
      Canada. STUDY POPULATION: administrators from 43 (97%) eligible programs
      consented to participate in the study. RESULTS: Network analysis revealed a
      diffuse system where centralization was greater in operational than
      administrative activities. A greater number of provider cliques were present at
      the operational level than the administrative level. Respondents identified
      several priorities to improve the coordination of cancer care in the community
      including: improving standards of care; establishing a regional coordinating
      body; increasing resources; and improving communication between programs.
      CONCLUSION: Our results point to the importance of developing a better
      understanding on the types of relationships that exist among service programs if
      effective integrated models of care are to be developed.

PMID- 18317560
TI  - An evaluation of a chronic disease prevention program in the Republika Srpska
      (RS) of Bosnia and Herzegovina.
AB  - INTRODUCTION: In 2002 the Republika Srpska of Bosnia and Herzegovina adopted
      goals for reducing the burden of chronic disease through a new screening program
      in its publicly funded health centers ("Dom Zdravljas"). This study evaluated the
      first year of program implementation. METHODS: The evaluation used in-depth
      interviews with 25 key stakeholders and in-person interviews with 1004 citizens.
      RESULTS: We found that many health care providers and citizens were unaware of
      the program. In addition, there was inadequate financing for the program, because
      the Health Insurance Fund does not collect revenue for uninsured citizens, more
      than 20 per cent of the population. CONCLUSION: We recommend improved co
      ordination among public and private organizations involved in implementation;
      increased promotion of the program with health care providers and citizens; and
      increased financial resources for providing screening for uninsured citizens.

PMID- 18317561
TI  - The effectiveness of the PRISMA integrated service delivery network: preliminary
      report on methods and baseline data.
AB  - PURPOSE: The PRISMA study analyzes an innovative coordination-type integrated
      service delivery (ISD) system developed to improve continuity and increase the
      effectiveness and efficiency of services, especially for older and disabled
      populations. The objective of the PRISMA study is to evaluate the effectiveness
      of this system to improve health, empowerment and satisfaction of frail older
      people, modify their health and social services utilization, without increasing
      the burden of informal caregivers. The objective of this paper is to present the
      methodology and give baseline data on the study participants. METHODS: A quasi
      experimental study with pre-test, multiple post-tests, and a comparison group was
      used to evaluate the impact of PRISMA ISD. Elders at risk of functional decline
      (501 experimental, 419 control) participated in the study. RESULTS: At entry, the
      two groups were comparable for most variables. Over the first year, when the
      implementation rate was low (32%), participants from the control group used fewer
      services than those from the experimental group. After the first year, no
      significant statistical difference was observed for functional decline and
      changes in the other outcome variables. CONCLUSION: This first year must be
      considered a baseline year, showing the situation without significant
      implementation of PRISMA ISD systems. Results for the following years will have
      to be examined with consideration of these baseline results.

PMID- 18317562
TI  - A stepped care programme for depression management: an uncontrolled pre-post
      study in primary and secondary care in The Netherlands.
AB  - INTRODUCTION: Stepped care strategies are potentially effective to organise
      integrated care but unknown is whether they function well in practice. This paper
      evaluates the implementation of a stepped care programme for depression in
      primary care and secondary care. THEORY AND METHODS: We developed a stepped care
      algorithm for diagnostics and treatment of depression, supported by a liaison
      consultation function. In a 2(1/2) year study with pre-post design in a pilot
      region, adherence to the protocol was assessed by interviewing 28 caregivers of
      235 patients with mild, moderate, or severe major depression. Consultation and
      referral patterns between primary and secondary care were analysed. RESULTS:
      Adherence of general practitioners and consultant caregivers to the stepped care
      protocol proved to be 96%. The percentage of patients referred for depression to
      secondary care decreased significantly from 26% to 21% (p=0.0180). In the post
      period more patients received treatment in primary care and requests for
      consultation became more concordant with the stepped care protocol. CONCLUSIONS:
      Implementation of a stepped care programme is feasible in a primary and secondary
      care setting and is associated with less referrals. DISCUSSION: Further research
      on all subsequent treatment steps in a standardised stepped care protocol is
      needed.

PMID- 18317563
TI  - Animal house.
AB  - While the JCI was originally conceived as a journal that would integrate various
      scientific approaches to the examination of human physiology and pathophysiology,
      we now find many of its pages filled with animal models of human disease. Is this
      a good thing?

PMID- 18317564
TI  - The comeback kid: TYSABRI now FDA approved for Crohn disease.

PMID- 18317565
TI  - Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin
      resistance: lessons from genetically engineered mice.
AB  - Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin
      resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases
      ranging from (i) fatty liver (hepatic steatosis); (ii) steatosis with
      inflammation and necrosis; and (iii) cirrhosis. Although the molecular mechanism
      leading to the development of hepatic steatosis in the pathogenesis of NAFLD is
      complex, recent animal models have shown that modulating important enzymes in
      fatty acid synthesis in liver may be key for the treatment of NAFLD. This review
      discusses recent advances in the field.

PMID- 18317566
TI  - Reduced immune complex binding capacity and increased complement susceptibility
      of red cells from children with severe malaria-associated anemia.
AB  - Plasmodium falciparum malaria causes 1-2 million deaths per year. Most deaths
      occur as a result of complications such as severe anemia and cerebral malaria
      (CM) (coma). Red cells of children with severe malaria-associated anemia (SMA)
      have acquired deficiencies in the complement regulatory proteins complement
      receptor 1 (CR1, CD35) and decay accelerating factor (DAF, CD55). We investigated
      whether these deficiencies affect the ability of erythrocytes to bind immune
      complexes (ICs) and regulate complement activation. We recruited 75 children with
      SMA (Hb < or = 6 g/dL) from the holoendemic malaria region of the Lake Victoria
      basin, western Kenya, and 74 age- and gender-matched uncomplicated malaria
      controls. In addition, we recruited 32 children with CM and 52 age- and gender
      matched controls. Deficiencies in red cell CR1 and CD55 in children with SMA were
      accompanied by a marked decline in IC binding capacity and increased C3b
      deposition in vivo and ex vivo. Importantly, these changes were specific because
      they were not seen in red cells of children with CM or their controls. These data
      suggest that the declines in red cell CR1 and CD55 seen in children with SMA are
      of physiologic significance and may predispose erythrocytes to complement
      mediated damage and phagocytosis in vivo.

PMID- 18317568
TI  - High Mobility Group Box Protein-1 correlates with renal function in chronic
      kidney disease (CKD).
AB  - Chronic kidney disease (CKD) is associated with inflammation and malnutrition and
      carries a markedly increased risk of cardiovascular disease (CVD). High Mobility
      Group Box Protein-1 (HMGB-1) is a 30-kDa nuclear and cytosolic protein known as a
      transcription and growth factor, recently identified as a proinflammatory
      mediator of tissue injury. Recent data implicates HMGB-1 in endotoxin lethality,
      rheumatoid arthritis, and atherosclerosis. The aim of this post-hoc, cross
      sectional study was to determine whether HMGB-1 serum levels are elevated in CKD
      patients. The study groups were categorized as follows: 110 patients starting
      dialysis defined as CKD 5; 67 patients with moderately to severely reduced renal
      function or CKD 3-4; and 48 healthy controls. High-sensitivity C-reactive-protein
      (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF), serum-albumin (S
      albumin), hemoglobin A(1c) (HbA(1c)), hemoglobin, subjective global nutritional
      assessment (SGA), and glomerular filtration rate (GFR) were analyzed. Kruskal
      Wallis test was used to compare groups and Spearman's rank correlation test was
      used for continuous variables. HMGB-1, measured by Western blot, was
      significantly (P < 0.001) elevated in CKD 5 (146.7 +/- 58.6 ng/mL) and CKD 3-4
      (85.6 +/- 31.8) compared with controls (10.9 +/- 10.5). HMGB-1 levels were
      correlated positively with TNF (Rho = 0.52; P < 0.001), hs-CRP (Rho = 0.38; P <
      0.001), IL-6 (Rho = 0.30; P < 0.001), HbA(1c) (Rho = 0.14; P = 0.02) and SGA (Rho
      = 0.21; P = 0.002) and negatively correlated with GFR (Rho = -0.69; P = 0.0001),
      Hb (Rho = -0.60; P < 0.001), S-albumin (Rho = -0.31; P < 0.001). The current
      study has revealed that HMGB-1 is elevated significantly in CKD patients and
      correlates with GFR as well as markers of inflammation and malnutrition. Future
      studies may delineate whether HMGB-1 is also a marker of disease activity and
      severity as well as a predictor of outcome in CKD.

PMID- 18317567
TI  - Iron-mediated inhibition of mitochondrial manganese uptake mediates mitochondrial
      dysfunction in a mouse model of hemochromatosis.
AB  - Previous phenotyping of glucose homeostasis and insulin secretion in a mouse
      model of hereditary hemochromatosis (Hfe(-/-)) and iron overload suggested
      mitochondrial dysfunction. Mitochondria from Hfe(-/-) mouse liver exhibited
      decreased respiratory capacity and increased lipid peroxidation. Although the
      cytosol contained excess iron, Hfe(-/-) mitochondria contained normal iron but
      decreased copper, manganese, and zinc, associated with reduced activities of
      copper-dependent cytochrome c oxidase and manganese-dependent superoxide
      dismutase (MnSOD). The attenuation in MnSOD activity was due to substantial
      levels of unmetallated apoprotein. The oxidative damage in Hfe(-/-) mitochondria
      is due to diminished MnSOD activity, as manganese supplementation of Hfe(-/-)
      mice led to enhancement of MnSOD activity and suppressed lipid peroxidation.
      Manganese supplementation also resulted in improved insulin secretion and glucose
      tolerance associated with increased MnSOD activity and decreased lipid
      peroxidation in islets. These data suggest a novel mechanism of iron-induced
      cellular dysfunction, namely altered mitochondrial uptake of other metal ions.

PMID- 18317570
TI  - RNAi and RNAa--the yin and yang of RNAome.
AB  - RNA interference (RNAi) is a powerful technology with huge applications for
      functional genomics, target identification in drug discovery and elucidation of
      molecular signaling pathways. Current RNAi studies have demonstrated the clinical
      potential of small interfering RNAs (siRNAs) in metabolic diseases, cancer, AIDS,
      malaria, neurodegenerative disorders, dental diseases and other illnesses.
      Interestingly, recent studies have shown that the small RNA molecules, either
      indigenously produced as microRNAs (miRNAs) or exogenously administered synthetic
      dsRNAs could effectively activate a particular gene in a sequence specific manner
      instead of silencing it. This novel, but still uncharacterized, phenomenon has
      been termed as RNA activation (RNAa). The paradoxical concept of Yin and Yang,
      which describe two primal opposing but complementary principles, can potentially
      be applied to elucidate the complex phenomenon of RNAa/RNAi in the RNAome. This
      warrants a proper understanding of the RNAi/RNAa molecular pathways in living
      organisms before any of the small dsRNAs can potentially be exploited for
      therapeutics in human beings.

PMID- 18317569
TI  - Presenilin-1 280Glu-->Ala mutation alters C-terminal APP processing yielding
      longer abeta peptides: implications for Alzheimer's disease.
AB  - Presenilin (PS) mutations enhance the production of the Abeta42 peptide that is
      derived from the amyloid precursor protein (APP). The pathway(s) by which the
      Abeta42 species is preferentially produced has not been elucidated, nor is the
      mechanism by which PS mutations produce early-onset dementia established. Using a
      combination of histological, immunohistochemical, biochemical, and mass
      spectrometric methods, we examined the structural and morphological nature of the
      amyloid species produced in a patient expressing the PS1 280Glu-->Ala familial
      Alzheimer's disease mutation. Abundant diffuse plaques were observed that
      exhibited a staining pattern and morphology distinct from previously described PS
      cases, as well as discreet amyloid plaques within the white matter. In addition
      to finding increased amounts of CT99 and Abeta42 peptides, our investigation
      revealed the presence of a complex array of Abeta peptides substantially longer
      than 42/43 amino acid residue species. The increased hydrophobic nature of longer
      Abeta species retained within the membrane walls could impact the structure and
      function of plasma membrane and organelles. These C-terminally longer peptides
      may, through steric effects, dampen the rate of turnover by critical amyloid
      degrading enzymes such as neprilysin and insulin degrading enzyme. A complete
      understanding of the deleterious side effects of membrane bound Abeta as a
      consequence of gamma-secretase alterations is needed to understand Alzheimer's
      disease pathophysiology and will aid in the design of therapeutic interventions.

PMID- 18317571
TI  - On the challenges of the HapMap resource.
AB  - The International HapMap Project provides a key resource of genotypic data on
      human lymphoblastoid cell lines derived from four major world populations of
      European, African, Chinese and Japanese ancestry for researchers to associate
      with various phenotypic data to find genes affecting health, disease and response
      to drugs. Recently, the HapMap resource has significantly benefited research
      areas such as gene expression variation studies. Besides some intrinsic
      limitations, there are a few challenges that should be considered in the next
      wave of research using this tremendous resource. We suggest that overcoming these
      challenges or considering the confounding variables in the interpretation of
      results can provide more insights into the current views of the human genome as
      well as complex traits such as drug response variation and susceptibility to
      common diseases.

PMID- 18317572
TI  - Proposed lead molecules against Hemagglutinin of avian influenza virus (H5N1).
AB  - Human infection with avian influenza H5N1 is an emerging infectious disease
      characterized by respiratory symptoms and a high fatality rate. Hemagglutinin and
      neuraminidase are the two surface proteins responsible for infection by influenza
      virus. Till date, neuraminidase has been the major target for antiviral drugs. In
      the present study we chose hemagglutinin protein as it mediates the binding of
      the virus to target cells through sialic acid residues on the host cell-surface.
      Hemagglutinin of H5 avian influenza (PDB ID: 1JSN) was used as the receptor
      protein. Ligands were generated by structure-based de novo approach and virtual
      screening of ZINC database. A total of 11,104 conformers were generated and
      docked into the receptor binding site using 'High Throughput Virtual Screening'.
      We proposed potential lead molecules against the receptor binding site of
      hemagglutinin based on the results obtained from in silico docking and hydrogen
      bond interaction between the ligand and the 1JSN protein molecule. We found
      sialic acid derivative 1 to be the lead molecules amongst the ligands generated
      by structure based de novo approach. However the molecules obtained from ZINC
      database were showing better docking scores as well as conserved hydrogen bond
      interactions. Thus we proposed ZINC00487720 and ZINC00046810 as potential lead
      molecules that could be used as an inhibitor to the receptor binding site of
      hemagglutinin. They could now be studied in vivo to validate the in silico
      results.

PMID- 18317573
TI  - MetaHuman genomics.

PMID- 18317574
TI  - SMARThivVLmos: a complexity-free and cost effective dynamic model technology for
      monitoring HIV viral load in resource-poor settings.
AB  - We design a "simple" and "low cost" model technology for monitoring HIV viral
      load in resource-poor settings: SMARThivVLmos. Cost and complexity are the major
      challenges to the developing world, in monitoring HIV patients viral load. We
      have previously demonstrated in our SMARThivPack model that cost and complexity
      of laboratory monitoring of HIV patients, may be reduced not only at a first
      technology development level, but also at a second technology implementation, and
      at a third global coordination levels. In our SMARThivPack model, the P24 HIV
      viral load monitoring system passed both the "cost" and the "complexity" tests.
      However, compared to other alternative viral monitoring systems such as the
      Cavidi EXAVIR, the sensitivity of the P24 system is too low. Here we describe a
      dynamic model technology that overcomes the sensitivity barrier of the P24 system
      while maintaining simplicity and low cost.

PMID- 18317575
TI  - Evaluation on the combined effect of Sesamin and Schisandra extract on blood
      fluidity.
AB  - Several studies have demonstrated a link between blood viscosity and various
      forms of liver dysfunction. Therefore, we investigated the effect of liver
      protective herbal materials, Sesamin combined with extract of Schisandra
      chinensis berry (Schisandra) for its potential to improve blood fluidity in
      humans. Ten human subjects were recruited to study the effect of sesamin combined
      with schisandra extract (SCH) for two weeks on blood viscosity. Blood fluidity
      was measured as the transit time for 100mul of heparinized whole blood to pass
      through a micro-channel array setup at baseline, 1 week and 2 weeks. For safety
      assessment, blood biochemistry, hematology and urine analysis were taken at
      baseline, 1 week and 2 weeks after SCH administration. No safety concern and
      adverse effects were observed during the 2-week continuous intake period. Intake
      of SCH reduced blood passage time by 9.0% and 9.7% at 1 and 2 weeks,
      respectively. In conclusion, this pilot clinical study indicates that the
      combined administration of sesamin with schisandra extract could improve blood
      fluidity after 1 week of oral intake and this effect was sustained up to 2 weeks.

PMID- 18317576
TI  - An SVM method using evolutionary information for the identification of allergenic
      proteins.
AB  - This study presents an allergenic protein prediction system that appears to be
      capable of producing high sensitivity and specificity. The proposed system is
      based on support vector machine (SVM) using evolutionary information in the form
      of an amino acid position specific scoring matrix (PSSM). The performance of this
      system is assessed by a 10-fold cross-validation experiment using a dataset
      consisting of 693 allergens and 1041 non-allergens obtained from Swiss-Prot and
      Structural Database of Allergenic Proteins (SDAP). The PSSM method produced an
      accuracy of 90.1% in comparison to the methods based on SVM using amino acid,
      dipeptide composition, pseudo (5-tier) amino acid composition that achieved an
      accuracy of 86.3, 86.5 and 82.1% respectively. The results show that evolutionary
      information can be useful to build more effective and efficient allergen
      prediction systems.

PMID- 18317577
TI  - SMARThivCD4mos: a complexity-free and cost effective model technology for
      monitoring HIV patients CD4 number in resource-poor settings.
AB  - We design a "simple" and "low cost" model technology for monitoring HIV patients
      CD4 number in resource-poor settings: SMARThivCD4mos. Cost and complexity are the
      major challenges to the developing world in transferring and implementing HIV
      surveillance technologies. We previously proposed a "three tests" combo kit model
      for improving HIV patients monitoring standards in resource-poor settings. From
      the pool of recommended alternative CD4 counting technologies, our "three tests"
      combo kit model retained the Capcellia technology for its "simplicity". However,
      compared to other CD4 counting technologies, such as Dynabeads, the Capcellia
      technology is "expensive". Here, we describe a cost reduction strategy of the
      Capcellia technology.

PMID- 18317578
TI  - A database on endemic plants at Tirumala hills in India.
AB  - Medicinal plants play an important role in health care. The use of medicinal
      plants for treatment is growing in view of cost and non-compliance of modern
      medicine as in case of non-communicable diseases. Plants such as Boswellia,
      ovalifoliolata, Cycas beddomei, Pimpinella tirupatiensis, Pterocarpus santalinus,
      Shorea thumbuggaia, Syzygium alternifolium, Terminalia pallida are endemic to
      Tirumala hills of seshachalam range falling under the Eastern Ghats of India.
      These plants species have medicinal properties such as anti-tumorogenic, anti
      microbial, purgative, hypoglycemic, abortificient, analgesic, anti-septic, anti
      pyretic and anti-inflammatory. We created a database named DEPTH in an attempt to
      communicate data of these plants to the scientific community. DEPTH contains data
      on scientific name, vernacular name, family name, morphological description,
      economic importance, known medicinal compounds and medicinal importance.
      AVAILABILITY: http://svimstpt.ap.nic.in/MedicinalPlants/mainpage.htm.

PMID- 18317579
TI  - RetroPred: A tool for prediction, classification and extraction of non-LTR
      retrotransposons (LINEs & SINEs) from the genome by integrating PALS, PILER, MEME
      and ANN.
AB  - The problem of predicting non-long terminal repeats (LTR) like long interspersed
      nuclear elements (LINEs) and short interspersed nuclear elements (SINEs) from the
      DNA sequence is still an open problem in bioinformatics. To elevate the quality
      of annotations of LINES and SINEs an automated tool "RetroPred" was developed.
      The pipeline allowed rapid and thorough annotation of non-LTR retrotransposons.
      The non-LTR retrotransposable elements were initially predicted by Pairwise
      Aligner for Long Sequences (PALS) and Parsimonious Inference of a Library of
      Elementary Repeats (PILER). Predicted non-LTR elements were automatically
      classified into LINEs and SINEs using ANN based on the position specific
      probability matrix (PSPM) generated by Multiple EM for Motif Elicitation (MEME).
      The ANN model revealed a superior model (accuracy = 78.79 +/- 6.86 %, Q(pred) =
      74.734 +/- 17.08 %, sensitivity = 84.48 +/- 6.73 %, specificity = 77.13 +/- 13.39
      %) using four-fold cross validation. As proof of principle, we have thoroughly
      annotated the location of LINEs and SINEs in rice and Arabidopsis genome using
      the tool and is proved to be very useful with good accuracy. Our tool is
      accessible at http://www.juit.ac.in/RepeatPred/home.html.

PMID- 18317580
TI  - Protein tyrosine phosphatases: new markers and targets in oncology?

PMID- 18317581
TI  - Canadian supportive care recommendations for the management of neutropenia in
      patients with cancer.
AB  - Hematologic toxicities of cancer chemotherapy are common and often limit the
      ability to provide treatment in a timely and dose-intensive manner. These
      limitations may be of utmost importance in the adjuvant and curative intent
      settings. Hematologic toxicities may result in febrile neutropenia, infections,
      fatigue, and bleeding, all of which may lead to additional complications and
      prolonged hospitalization. The older cancer patient and patients with significant
      comorbidities may be at highest risk of neutropenic complications. Colony
      stimulating factors (csfs) such as filgrastim and pegfilgrastim can effectively
      attenuate most of the neutropenic consequences of chemotherapy, improve the
      ability to continue chemotherapy on the planned schedule, and minimize the risk
      of febrile neutropenia and infectious morbidity and mortality. The present
      consensus statement reviews the use of csfs in the management of neutropenia in
      patients with cancer and sets out specific recommendations based on published
      international guidelines tailored to the specifics of the Canadian practice
      landscape. We review existing international guidelines, the indications for
      primary and secondary prophylaxis, the importance of maintaining dose intensity,
      and the use of csfs in leukemia, stem-cell transplantation, and radiotherapy.
      Specific disease-related recommendations are provided related to breast cancer,
      non-Hodgkin lymphoma, lung cancer, and gastrointestinal cancer. Finally, csf
      dosing and schedules, duration of therapy, and associated acute and potential
      chronic toxicities are examined.

PMID- 18317582
TI  - Cardiac management during adjuvant trastuzumab therapy: recommendations of the
      Canadian Trastuzumab Working Group.
AB  - Trastuzumab has been shown to be an effective therapy for women with breast
      cancer that overexpresses the human epidermal growth factor receptor 2 (her2)
      protein. In the pivotal metastatic breast cancer trials, cardiac dysfunction was
      observed in women treated with trastuzumab and chemotherapy. The incidence and
      severity of cardiac dysfunction was greatest among patients who received
      trastuzumab in combination with anthracycline-based therapy. Those findings
      influenced the design of subsequent trastuzumab trials to include prospective
      evaluations of cardiac effects and protocols for cardiac monitoring and
      management. The risk of cardiotoxicity has also driven efforts to develop non
      anthracycline-based regimens for women with her2-positive breast cancers.With the
      increasing use of trastuzumab, particularly in the curative adjuvant setting, the
      need for a rational approach to the treatment and cardiac management of the
      relevant patient population is clear. The mandate of the Canadian Trastuzumab
      Working Group was to formulate recommendations, based on available data, for the
      assessment and management of cardiac complications during adjuvant trastuzumab
      therapy. The panel formulated recommendations in four areas: Risk factors for
      cardiotoxicity, Effects of various regimens, Monitoring, Management. The
      recommendations published here are expected to evolve as more data become
      available and experience with trastuzumab in the adjuvant setting grows.

PMID- 18317583
TI  - Health management program: factors influencing completion of therapy with high
      dose interferon alfa-2b for high-risk melanoma.
AB  - The goal of the 1-year observational, multicentre, open-label study reported here
      was to identify factors influencing adherence to high-dose interferon alfa-2b
      adjuvant therapy in patients at high risk of recurrence following surgical
      excision of malignant melanoma. The study was carried out in 23 tertiary-care
      centres across Canada.The 225 patients enrolled in the study all had malignant
      melanoma that was surgically excised and that required adjuvant treatment with
      interferon alfa-2b. Of these patients, 64% were men. Mean age was 51.7 years. All
      patients received interferon alfa-2b treatment during a 4-week induction phase
      (20 MU/m(2) intravenously 5 days per week) followed by a 48-week maintenance
      phase (10 MU/m(2) subcutaneously 3 days per week).Oncology nurses reviewed side
      effect management with the patients before the induction and maintenance phases.
      Patients were provided with daily diaries, comprehensive educational materials,
      and ongoing nursing support. Data on side effects and discontinuations were
      obtained from patient interviews and diaries. THE MAIN OUTCOME MEASUREMENTS WERE
      RELATED TO TREATMENT DISCONTINUATION: rate, timing, reason, and prevention. Of
      the 225 patients, 75 (33.3%) discontinued interferon during the induction phase,
      and 58 (25.8%) discontinued during the maintenance phase. The main reasons for
      discontinuation were adverse events (58%) and disease progression (26%). Patients
      with a daily fluid intake greater than 1.5 L were more likely to complete therapy
      than were those with an intake less than 1.5 L (64% vs. 36%, p < 0.0001).Of 225
      patients enrolled in the interferon alfa-2b health management program, 41%
      completed the 1-year treatment course. Higher fluid intake (>1.5 L daily) was
      associated with increased adherence to therapy.

PMID- 18317584
TI  - Chinese medicine and biomodulation in cancer patients--Part one.
AB  - Traditional Chinese Medicine (tcm) may be integrated with conventional Western
      medicine to enhance the care of patients with cancer. Although tcm is normally
      implemented as a whole system, recent reductionist research suggests mechanisms
      for the effects of acupuncture, herbs, and nutrition within the scientific model
      of biomedicine. The health model of Chinese medicine accommodates physical and
      pharmacologic interventions within the framework of a body-mind network. A
      Cartesian split does not occur within this model, but to allow for scientific
      exploration within the restrictions of positivism, reductionism, and controls for
      confounding factors, the components must necessarily be separated. Still, whole
      systems research is important to evaluate effectiveness when applying the full
      model in clinical practice. Scientific analysis provides a mechanistic
      understanding of the processes that will improve the design of clinical studies
      and enhance safety. Enough preliminary evidence is available to encourage quality
      clinical trials to evaluate the efficacy of integrating tcm into Western cancer
      care.

PMID- 18317585
TI  - The Ontario cancer research ethics board: a central REB that works.
AB  - The Ontario Cancer Research Ethics Board (ocreb) has made its mark within Ontario
      as a successful, centralized, oncology-specific research ethics board. As such,
      ocreb has proven invaluable to principal investigators, sponsors, and study
      participants given its ability to reduce duplication during the submission
      process, to provide the highest quality of review, to shorten study start-up
      time, and to implement more efficient methods of reporting serious adverse
      events.

PMID- 18317586
TI  - Radiation recall dermatitis: case report and review of the literature.
AB  - "Radiation recall"-also called "radiation recall dermatitis"-has been defined as
      the "recalling" by skin of previous radiation exposure in response to the
      administration of certain response-inducing drugs. Although the phenomenon is
      relatively well known in the medical world, an exact cause has not been
      documented. Here, we report a rare occurrence of the radiation recall phenomenon
      in a breast cancer patient after palliative radiotherapy for bone, brain, and
      orbital metastases.

PMID- 18317587
TI  - "Crack lung and heart" presenting after chemotherapy in a 65-year-old man with
      non-Hodgkin lymphoma.
AB  - Crack cocaine can cause a variety of pulmonary and cardiac complications.
      Pulmonary findings in a 65- year-old man with non-Hodgkin lymphoma who presented
      with shortness of breath not resolving with antibiotics are presented here. The
      usual manifestation of "crack lung" in an unusual clinical circumstance
      underlines the importance of a clinical history in such cases. The finding of
      "crack lung" preceded the diagnosis of probable "crack heart." No other similar
      published case reports could be identified in the literature.

PMID- 18317588
TI  - Trastuzumab in the adjuvant setting: concurrent or sequential? It takes two to
      tango!

PMID- 18317590
TI  - Interactions between integrin alphaIIbbeta3 and the serotonin transporter
      regulate serotonin transport and platelet aggregation in mice and humans.
AB  - The essential contribution of the antidepressant-sensitive serotonin (5-HT)
      transporter SERT (which is encoded by the SLC6A4 gene) to platelet 5-HT stores
      suggests an important role of this transporter in platelet function. Here, using
      SERT-deficient mice, we have established a role for constitutive SERT expression
      in efficient ADP- and thrombin-triggered platelet aggregation. Additionally,
      using pharmacological blockers of SERT and the vesicular monoamine transporter
      (VMAT), we have identified a role for ongoing 5-HT release and SERT activity in
      efficient human platelet aggregation. We have also demonstrated that fibrinogen,
      an activator of integrin alphaIIbbeta3, enhances SERT activity in human platelets
      and that integrin alphaIIbbeta3 interacts directly with the C terminus of SERT.
      Consistent with these findings, knockout mice lacking integrin beta3 displayed
      diminished platelet SERT activity. Conversely, HEK293 cells engineered to express
      human SERT and an activated form of integrin beta3 exhibited enhanced SERT
      function that coincided with elevated SERT surface expression. Our results
      support an unsuspected role of alphaIIbbeta3/SERT associations as well as
      alphaIIbbeta3 activation in control of SERT activity in vivo that may have broad
      implications for hyperserotonemia, cardiovascular disorders, and autism.

PMID- 18317591
TI  - In vivo time-lapse microscopy reveals no loss of murine myonuclei during weeks of
      muscle atrophy.
AB  - Numerous studies have suggested that muscle atrophy is accompanied by apoptotic
      loss of myonuclei and therefore recovery would require replenishment by muscle
      stem cells. We used in vivo time-lapse microscopy to observe the loss and
      replenishment of myonuclei in murine muscle fibers following induced muscle
      atrophy. To our surprise, imaging of single fibers for up to 28 days did not
      support the concept of nuclear loss during atrophy. Muscles were inactivated by
      denervation, nerve impulse block, or mechanical unloading. Nuclei were stained in
      vivo either acutely by intracellular injection of fluorescent oligonucleotides or
      in time-lapse studies after transfection with a plasmid encoding GFP with a
      nuclear localization signal. We observed no loss of myonuclei in fast- or slow
      twitch muscle fibers despite a greater than 50% reduction in fiber cross
      sectional area. TUNEL labeling of fragmented DNA on histological sections
      revealed high levels of apoptotic nuclei in inactive muscles. However, when
      costained for laminin and dystrophin, virtually none of the TUNEL-positive nuclei
      could be classified as myonuclei; apoptosis was confined to stromal and satellite
      cells. We conclude that disuse atrophy is not a degenerative process, but is
      rather a change in the balance between protein synthesis and proteolysis in a
      permanent cell syncytium.

PMID- 18317592
TI  - Estrogen receptor beta protects against acoustic trauma in mice.
AB  - The hormone estradiol affects the auditory system both by itself and by its
      interaction with neuroprotective factors. In this study, we examined the role of
      estrogen receptors (ERs) in response to auditory trauma. We found a ligand
      dependent protective role for ERbeta in the auditory system by investigating mice
      deficient in ERalpha (ERKO mice), ERbeta (BERKO mice), and aromatase (ARKO mice).
      Basal auditory brainstem response (ABR) thresholds were similar in all animals.
      An acoustic trauma causing a temporary hearing loss raised ABR thresholds in male
      and female BERKO and ARKO mice compared with WT and ERKO mice. The ERalpha
      selective agonist, propyl(1H) pyrazole-1,3,5-triyl-trisphenol (PPT), partially
      protected ARKO mice from trauma, while the ERbeta-selective agonist, 2,3-bis (4
      hydroxyphenyl)-propionitrile (DPN), protected WT and ARKO mice.
      Immunohistochemistry and western blotting confirmed the expression of ERbeta in
      cochlea of WT males and females. Levels of brain-derived neurotrophic factor
      (BDNF), a neuroprotective peptide that can be induced by estrogen, was lower in
      BERKO and ARKO mice compared with WT. DPN treatment increased BDNF expression in
      ARKO mice. These data indicate ERbeta-mediated neuroprotection involving BDNF in
      the auditory system of males and females.

PMID- 18317593
TI  - Leptin resistance contributes to obesity and hypertension in mouse models of
      Bardet-Biedl syndrome.
AB  - Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by
      many features, including obesity and cardiovascular disease. We previously
      developed knockout mouse models of 3 BBS genes: BBS2, BBS4, and BBS6. To dissect
      the mechanisms involved in the metabolic disorders associated with BBS, we
      assessed the development of obesity in these mouse models and found that BBS-null
      mice were hyperphagic, had low locomotor activity, and had elevated circulating
      levels of the hormone leptin. The effect of exogenous leptin on body weight and
      food intake was attenuated in BBS mice, which suggests that leptin resistance may
      contribute to hyperleptinemia. In other mouse models of obesity, leptin
      resistance may be selective rather than systemic; although mice became resistant
      to leptin's anorectic effects, the ability to increase renal sympathetic nerve
      activity (SNA) was preserved. Although all 3 of the BBS mouse models were
      similarly resistant to leptin, the sensitivity of renal SNA to leptin was
      maintained in Bbs4 -/- and Bbs6 -/- mice, but not in Bbs2 -/- mice. Consequently,
      Bbs4 -/- and Bbs6 -/- mice had higher baseline renal SNA and arterial pressure
      and a greater reduction in arterial pressure in response to ganglionic blockade.
      Furthermore, we found that BBS mice had a decreased hypothalamic expression of
      proopiomelanocortin, which suggests that BBS genes play an important role in
      maintaining leptin sensitivity in proopiomelanocortin neurons.

PMID- 18317594
TI  - Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced
      apoptosis of human sebaceous gland cells.
AB  - 13-cis retinoic acid (13-cis RA; also known as isotretinoin) is the most potent
      agent available for treatment of acne. It is known that the drug induces
      apoptosis in cells cultured from human sebaceous glands, but its mechanism of
      action has not been determined. In this study, skin biopsies were taken from 7
      patients with acne prior to and at 1 week of treatment with 13-cis RA. TUNEL
      staining confirmed that 13-cis RA induced apoptosis in sebaceous glands.
      Transcriptional profiling of patient skin and cultured human sebaceous gland
      cells (SEB-1 sebocytes) indicated that lipocalin 2 was among the genes most
      highly upregulated by 13-cis RA. Lipocalin 2 encodes neutrophil gelatinase
      associated lipocalin (NGAL), which functions in innate immune defense and induces
      apoptosis of murine B lymphocytes. Increased immunolocalization of NGAL was noted
      in patients' sebaceous glands following treatment with 13-cis RA, and recombinant
      NGAL induced apoptosis in SEB-1 sebocytes. Furthermore, apoptosis in response to
      13-cis RA was inhibited in the presence of siRNA to lipocalin 2. These data
      indicate that NGAL mediates the apoptotic effect of 13-cis RA and suggest that
      agents that selectively induce NGAL expression in sebaceous glands might
      represent therapeutic alternatives to the use of 13-cis RA to treat individuals
      with acne.

PMID- 18317595
TI  - IFN-gamma- and TNF-dependent bystander eradication of antigen-loss variants in
      established mouse cancers.
AB  - Tumors elicit antitumor immune responses, but over time they evolve and can
      escape immune control through various mechanisms, including the loss of the
      antigen to which the response is directed. The escape of antigen-loss variants
      (ALVs) is a major obstacle to T cell-based immunotherapy for cancer. However,
      cancers can be cured if both the number of CTLs and the expression of antigen are
      high enough to allow targeting of not only tumor cells, but also the tumor
      stroma. Here, we showed that IFN-gamma and TNF produced by CTLs were crucial for
      the elimination of established mouse tumors, including ALVs. In addition, both BM
      and non-BM-derived stromal cells were required to express TNF receptors and IFN
      gamma receptors for the elimination of ALVs. Although IFN-gamma and TNF were not
      required by CTLs for perforin-mediated killing of antigen-expressing tumor cells,
      the strong inference is that tumor antigen-specific CTLs must secrete IFN-gamma
      and TNF for destruction of tumor stroma. Therefore, bystander killing of ALVs may
      result from IFN-gamma and TNF acting on tumor stroma.

PMID- 18317596
TI  - Targeted mutation of mouse skeletal muscle sodium channel produces myotonia and
      potassium-sensitive weakness.
AB  - Hyperkalemic periodic paralysis (HyperKPP) produces myotonia and attacks of
      muscle weakness triggered by rest after exercise or by K+ ingestion. We
      introduced a missense substitution corresponding to a human familial HyperKPP
      mutation (Met1592Val) into the mouse gene encoding the skeletal muscle voltage
      gated Na+ channel NaV1.4. Mice heterozygous for this mutation exhibited prominent
      myotonia at rest and muscle fiber-type switching to a more oxidative phenotype
      compared with controls. Isolated mutant extensor digitorum longus muscles were
      abnormally sensitive to the Na+/K+ pump inhibitor ouabain and exhibited age
      dependent changes, including delayed relaxation and altered generation of tetanic
      force. Moreover, rapid and sustained weakness of isolated mutant muscles was
      induced when the extracellular K+ concentration was increased from 4 mM to 10 mM,
      a level observed in the muscle interstitium of humans during exercise. Mutant
      muscle recovered from stimulation-induced fatigue more slowly than did control
      muscle, and the extent of recovery was decreased in the presence of high
      extracellular K+ levels. These findings demonstrate that expression of the
      Met1592ValNa+ channel in mouse muscle is sufficient to produce important features
      of HyperKPP, including myotonia, K+-sensitive paralysis, and susceptibility to
      delayed weakness during recovery from fatigue.

PMID- 18317598
TI  - Efficiency to enable equitable inclusion in relation to new technology.

PMID- 18317597
TI  - Premature termination codons in PRPF31 cause retinitis pigmentosa via
      haploinsufficiency due to nonsense-mediated mRNA decay.
AB  - Dominant mutations in the gene encoding the mRNA splicing factor PRPF31 cause
      retinitis pigmentosa, a hereditary form of retinal degeneration. Most of these
      mutations are characterized by DNA changes that lead to premature termination
      codons. We investigated 6 different PRPF31 mutations, represented by single-base
      substitutions or microdeletions, in cell lines derived from 9 patients with
      dominant retinitis pigmentosa. Five of these mutations lead to premature
      termination codons, and 1 leads to the skipping of exon 2. Allele-specific
      measurement of PRPF31 transcripts revealed a strong reduction in the expression
      of mutant alleles. As a consequence, total PRPF31 protein abundance was
      decreased, and no truncated proteins were detected. Subnuclear localization of
      the full-length PRPF31 that was present remained unaffected. Blocking nonsense
      mediated mRNA decay significantly restored the amount of mutant PRPF31 mRNA but
      did not restore the synthesis of mutant proteins, even in conjunction with
      inhibitors of protein degradation pathways. Our results indicate that most PRPF31
      mutations ultimately result in null alleles through the activation of
      surveillance mechanisms that inactivate mutant mRNA and, possibly, proteins.
      Furthermore, these data provide compelling evidence that the pathogenic effect of
      PRPF31 mutations is likely due to haploinsufficiency rather than to gain of
      function.

PMID- 18317599
TI  - Phonological performance measured by speech severity indices compared with
      correlated factors.
AB  - CONTEXT AND OBJECTIVE: Some factors seem to influence speech impairment among
      phonologically disordered children. The aim was to compare severity indices with
      some correlated factors. DESIGN AND SETTING: Observational, analytical and cross
      sectional study conducted within the Language-Speech-Hearing Sciences Course,
      Universidade de Sao Paulo. METHOD: Fifty phonologically disordered children with
      ages ranging from 4 to 11 years took part. The indices were calculated from
      phonology tests and were correlated with anamnesis and audiological data.
      Students t test and Spearmans correlation were used to compare percentages of
      consonants correct (PCC) and process density index (PDI) for children with and
      without otitis, upper respiratory histories and audiological abnormalities, with
      regard to whether or not they were comprehended during assessment, their ages
      when they started to speak and their ages at the assessment. RESULTS: The higher
      the age at the assessment was, the higher the PCC (imitation: 0.468; naming:
      0.431; Spearmans correlation) and the lower the PDI (imitation: 0.459; naming:
      0.431); the later the child started to speak, the lower the PCC (imitation p =
      0.064; naming p = 0.050) and the higher the PDI (imitation p = 0.067; naming p =
      0.042). There were differences between groups with and without upper respiratory
      history (PCC: imitation p = 0.016, naming p = 0.005; PDI: imitation p = 0.014,
      naming p = 0.008). There was no difference between the groups regarding otitis,
      comprehension during the assessment and audiological data. CONCLUSIONS: Children
      with upper respiratory histories who began to speak later presented more severe
      speech impairment indices.

PMID- 18317600
TI  - Prognostic factors for perioperative pulmonary events among patients undergoing
      upper abdominal surgery.
AB  - CONTEXT AND OBJECTIVE: The significant relationship between upper abdominal
      surgery and early (perioperative) pulmonary events was investigated among
      patients with preoperative pulmonary conditions undergoing general anesthesia.
      DESIGN AND SETTING: Retrospective study for which data were obtained
      prospectively from 1999 to 2004, at a tertiary university hospital. METHODS: We
      retrospectively studied 3107 patients over 11 years old presenting American
      Society of Anesthesiologists (ASA) status I, II or III who underwent upper
      abdominal surgery under general anesthesia and were discharged to the recovery
      room. The preoperative conditions analyzed using logistic regression were: age,
      sex, ASA physical status, congestive heart failure, asthma, chronic obstructive
      pulmonary disease (COPD), respiratory failure and smoking. The outcomes or
      dependent variables included intraoperative and postoperative events:
      bronchospasm, hypoxemia, hypercapnia, prolonged intubation and airway secretion.
      RESULTS: Among these patients (1500 males, 1607 females, mean age 48 years, 1088
      ASA I, 1402 ASA II and 617 ASA III), there were 80 congestive heart failures, 82
      asthmatics, 122 with COPD, 21 respiratory failures and 428 smokers. Logistic
      regression analysis showed that female sex (p < 0.001), age over 70 years (p <
      0.01), smoking (p < 0.001) and COPD (p < 0.02) significantly influenced pulmonary
      event development, particularly hypoxemia and bronchospasm, at both times but not
      in the same patients. Asthma and congestive heart failure cases did not present
      pulmonary events in the recovery room. CONCLUSION: In upper abdominal surgery
      under general anesthesia, female sex, age over 70, smoking and COPD were
      independent risk factors for intra and postoperative pulmonary events.

PMID- 18317601
TI  - Effectiveness and safety of endotracheal tube cuffs filled with air versus filled
      with alkalinized lidocaine: a randomized clinical trial.
AB  - CONTEXT AND OBJECTIVE: High intracuff pressure in endotracheal tubes (ETs) may
      cause tracheal lesions. The aim of this study was to evaluate the effectiveness
      and safety of endotracheal tube cuffs filled with air or with alkalinized
      lidocaine. DESIGN AND SETTING: This was a prospective clinical study at the
      Department of Anesthesiology, Faculdade de Medicina de Botucatu, Universidade
      Estadual Paulista. METHODS: Among 50 patients, ET cuff pressures were recorded
      before, 30, 60, 90 and 120 minutes after starting and upon ending nitrous oxide
      anesthesia. The patients were randomly allocated to two groups: Air, with ET cuff
      inflated with air to attain a cuff pressure of 20 cmH2O; and Lido, with ET cuff
      filled with 2% lidocaine plus 8.4% sodium bicarbonate to attain the same
      pressure. ET discomfort before tracheal extubation, and sore throat, hoarseness
      and coughing incidence were studied at the time of discharge from the post
      anesthesia care unit, and sore throat and hoarseness were studied 24 hours after
      anesthesia. RESULTS: Pressures in Lido cuffs were significantly lower than in Air
      cuffs (p < 0.05). Tracheal complaints were similar for the two groups, except for
      lower ET discomfort and sore throat incidence after 24 hours and lower systolic
      arterial pressure at the time of extubation in the Lido group (p < 0.05).
      CONCLUSION: ET cuffs filled with alkalinized lidocaine prevented the occurrence
      of high cuff pressures during N2O anesthesia and reduced ET discomfort and
      postoperative sore throat incidence. Thus, alkalinized lidocaine-filled ET cuffs
      seem to be safer than conventional air-filled ET cuffs.

PMID- 18317602
TI  - Cholelithiasis and biliary sludge in Downs syndrome patients.
AB  - CONTEXT AND OBJECTIVE: Although studies have demonstrated increased frequency of
      gallbladder abnormalities among Downs syndrome (DS) patients in some countries,
      there is only one paper on this subject in the Brazilian literature. The aim of
      this study was to demonstrate the prevalence, clinical characteristics and
      evolution of lithiasis and biliary sludge among DS patients in a maternity and
      childrens hospital in Rio de Janeiro. DESIGN AND SETTING: This was a cross
      sectional study followed by a retrospective cohort study on all individuals with
      an ultrasound diagnosis of gallbladder abnormalities. METHODS: 547 DS patients
      (53.2% male, 46.8% female) attending the Instituto Fernandes Figueira in 2001
      underwent abdominal ultrasound examination at ages of between one day and three
      years (mean: five months). Clinical and ultrasound data were analyzed. RESULTS:
      In 50 patients (9.1%), the ultrasound demonstrated gallbladder abnormalities
      (6.9% lithiasis and 2.1% biliary sludge). Spontaneous resolution was observed in
      66.7% of the patients with biliary sludge and 28.9% with lithiasis.
      Cholecystectomy was carried out on 26.3% of the patients with gallstones.
      CONCLUSION: The results from this study and comparison with the literature
      suggest that DS patients are at risk of developing lithiasis and biliary sludge
      and should be monitored throughout the neonatal period, even if there are no
      known risk factors for gallstone formation. Most frequently, these gallbladder
      abnormalities occur without symptoms and spontaneously resolve in most non
      symptomatic patients. DS patients should be monitored with serial abdominal
      ultrasound, and cholecystectomy is indicated for symptomatic cases or when
      cholecystitis is present.

PMID- 18317603
TI  - Non-alcoholic fatty liver disease and metabolic syndrome in Brazilian middle-aged
      and older adults.
AB  - CONTEXT AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a complex
      clinicopathological entity characterized by diffuse or focal fat accumulation in
      the hepatic parenchyma of patients who deny abusive alcohol consumption. This
      study aimed to assess idiopathic NAFLD in community-dwelling, middle-aged and
      older adults living in the Brazilian Federal District. Associations between NAFLD
      and components of metabolic syndrome and the whole syndrome were investigated.
      DESIGN AND SETTINGS: This was a cross-sectional study on 139 subjects aged 55
      years or older. METHODS: NAFLD was diagnosed by means of clinical procedures, to
      exclude subjects with signs of liver disorders, abusive alcohol consumption and
      influence from hepatotoxic drugs. Phenotypes were graded based on ultrasound
      examination. Metabolic syndrome was defined using the NCEP ATP III criteria.
      Laboratory tests were performed to assist clinical examinations and define the
      syndrome. RESULTS NAFLD was present in 35.2% of the subjects. Taken together, the
      two most intense phenotypes correlated with increased serum fasting glucose,
      triglyceride and VLDL cholesterol levels. Metabolic syndrome was diagnosed in
      25.9% of the sample. In addition to associating NAFLD with specific traits of
      metabolic syndrome, non-parametric analysis confirmed the existence of a
      relationship (p < 0.05) between the steatotic manifestation and the syndromic
      condition. CONCLUSION: Compared with the literature, this study reveals greater
      frequency of idiopathic NAFLD among Brazilian middle-aged and older adults than
      is described elsewhere. The findings also suggest that impaired glycemic
      metabolism coupled with increased fat delivery and/or sustained endogenous
      biosynthesis is the most likely physiopathogenic mechanisms underlying the onset
      of NAFLD in this population.

PMID- 18317604
TI  - Hysteroscopy as a standard procedure for assessing endometrial lesions among
      postmenopausal women.
AB  - CONTEXT AND OBJECTIVES: Endometrial cancer is the most prevalent type of
      malignant neoplasia of the genital tract. The objective of this study was to
      calculate the sensitivity, specificity, accuracy and positive and negative
      predictive values for diagnostic hysteroscopy, in comparison with
      histopathological tests, for all lesions of the endometrial cavity. DESIGN AND
      SETTING: Retrospective descriptive study at the public tertiary-level university
      hospital of Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo.
      METHODS: Diagnostic hysteroscopy was indicated in the following instances:
      endometrial thickness > 4 mm in asymptomatic patients; postmenopausal bleeding;
      and irregular endometrium or endometrium difficult to assess from ultrasound,
      with or without vaginal bleeding. Ultrasound evaluations were carried out no more
      than three months prior to hysteroscopy. RESULTS: There were 510 patients, with a
      mean age of 61.1+/-2.0 years and mean time elapsed since the menopause of 12.7+/
      2.5 years. Endometrial biopsies were performed on 293 patients (57.5%).
      Histopathological analysis showed that 18 patients presented endometrial
      carcinoma or typical or atypical hyperplasia, and none of them presented
      endometrial thickness of less than 8 mm. No significant differences were found
      between the median thicknesses of the various benign lesions (p > 0.05). In our
      data, the sensitivity, specificity, accuracy and positive and negative predictive
      values for cancer or hyperplasia were 94.4%, 97.0%, 96.8%, 68% and 99.6%,
      respectively. CONCLUSIONS: Our results suggest that hysteroscopy is valuable as a
      diagnostic tool for malignant/hyperplastic and benign lesions, except for
      submucous myomas, for which the sensitivity was only 52.6%.

PMID- 18317605
TI  - Efficacy of estriol in inhibiting epithelial proliferation in mammary
      fibroadenoma: randomized clinical trial.
AB  - CONTEXT AND OBJECTIVE: Mammary fibroadenoma is a disease that affects a large
      number of women of reproductive age. The aim of this study was to evaluate the
      proliferative activity of mammary fibroadenoma through expression of Ki-67 and c
      myc antigens, following administration of oral contraceptive with or without
      estriol. DESIGN AND SETTING: Placebo-controlled double-blind randomized clinical
      trial in the Mastology Sector of the Department of Gynecology, Universidade
      Federal de Sao Paulo. METHODS: Thirty-three fibroadenoma patients were studied.
      Ten women (group 1) took an oral contraceptive constituted by levonorgestrel and
      ethinyl estradiol together with placebo manufactured in the same capsule for four
      consecutive cycles with a seven-day interval between them. The other 23 patients
      (group 2) took the same oral contraceptive together with estriol, which was put
      into the same capsule and used in the same way as among the group 1 patients.
      After four cycles, the nodules were surgically removed and sent for
      immunohistochemical analysis of Ki-67 and c-myc expression. RESULTS: The Ki-67
      and c-myc analysis did not reveal any significant differences between the study
      groups. The values were 9.16 and 10.54 for group 1 and 10.86 and 17.03 for group
      2, respectively. There was a tendency towards higher expression of antigens in
      group 2. CONCLUSION: Our results showed that there was no significant statistical
      difference in Ki-67 and c-myc expression between our study groups, but only a
      tendency towards higher expression among users of oral contraceptives containing
      estriol.

PMID- 18317606
TI  - Ossification of caroticoclinoid ligament and its clinical importance in skull
      based surgery.
AB  - CONTEXT: The medial end of the posterior border of the sphenoid bone presents the
      anterior clinoid process (ACP), which is usually accessed for operations
      involving the clinoid space and the cavernous sinus. The ACP is often connected
      to the middle clinoid process (MCP) by a ligament known as the caroticoclinoid
      ligament (CCL), which may be ossified, forming the caroticoclinoid foramen (CCF).
      Variations in the ACP other than ossification are rare. The ossified CCL may have
      compressive effects on the internal carotid artery. Thus, anatomical and
      radiological knowledge of the ACP and the clinoid space is also important when
      operating on the internal carotid artery. Excision of the ACP may be required for
      many skull-based surgical procedures, and the presence of any anomalies such as
      ossified CCL may pose a problem for neurosurgeons. CASE REPORT: We observed the
      presence of ossified CCL in a skull bone. A detailed radiological study of the
      CCL and the CCF was conducted. Morphometric measurements were recorded and
      photographs were taken. The ACP was connected to the MCP and was converted into a
      CCF. Considering the fact that standard anatomy textbooks do not provide
      morphological descriptions and radiological evaluations of the CCL, the present
      study may be important for neurosurgeons operating in the region of the ACP.

PMID- 18317607
TI  - Treatment of Fraleys syndrome by upper-pole nephrectomy.
AB  - CONTEXT: Fraleys syndrome is characterized by vascular compression on the
      superior infundibulum with secondary dilatation of the upper pole calyx, mostly
      located on the right side. CASE REPORT: We present the case of a 22-year-old
      woman with vascular compression of the upper-pole infundibulocalyceal system
      (Fraleys syndrome). The patient had a history of frequent hospitalizations for
      emergency care due to lumbar pain over the past twelve months. The diagnosis was
      obtained following renal arteriography. Since the surgical treatment by means of
      upper-pole nephrectomy, the patient has not had any further symptoms.

PMID- 18317608
TI  - Chronic idiopathic intestinal pseudo-obstruction treated with jejunostomy: case
      report and literature review.
AB  - CONTEXT: Chronic idiopathic intestinal pseudo-obstruction is a very rare
      condition. CASE REPORT: This study describes a male patient who had presented
      obstructive symptoms for 24 years. He had been treated clinically and had
      undergone two previous operations in different services, with no clinical
      improvement or correct diagnosis. He was diagnosed with intestinal obstruction
      without mechanical factors in our service and underwent jejunostomy, which had a
      significant decompressive effect. The patient was able to gain weight and
      presented improvements in laboratory tests. Jejunostomy is a relatively simple
      surgical procedure that is considered palliative but, in this case, it was
      resolutive.

PMID- 18317609
TI  - A systematic review of the interventions to promote the wearing of hearing
      protection.
AB  - CONTEXT AND OBJECTIVE: Noise-induced hearing loss can only be prevented by
      eliminating or lowering noise exposure levels. When the source of the noise
      cannot be eliminated, workers have to rely on hearing protection equipment. The
      aim here was to summarize the evidence for the effectiveness of interventions to
      enhance the wearing of hearing protection among workers exposed to noise in the
      workplace. DATA SOURCE: Studies with random assignment were identified by an
      electronic search of the medical literature up to 2005. Data were double-entered
      into the Review Manager software, version 4.2.5. DATA SYNTHESIS: Two studies were
      found. A computer-based intervention tailored to individual workers risks and
      lasting 30 minutes was not found to be more effective than a video providing
      general information for workers. A second randomized controlled trial evaluated
      the effect of a four-year school-based hearing loss prevention program among
      schoolchildren working on their parents farms. The intervention group was twice
      as likely to wear some kind of hearing protection as was the control group (which
      received only minimal intervention). REVIEWERS CONCLUSIONS: The limited evidence
      does not show whether tailored interventions are more or less effective than
      general interventions among workers, 80% of whom already use hearing protection.
      Long-lasting school-based interventions may increase the use of hearing
      protection substantially. Better interventions to enhance the use of hearing
      protection need to be developed and evaluated in order to increase the prevention
      of noise-induced hearing loss among workers.

PMID- 18317610
TI  - Psychosocial, health and demographic characteristics of quality of life among
      patients with acute myeloid leukemia and malignant lymphoma who underwent
      autologous hematopoietic stem cell transplantation.
AB  - CONTEXT AND OBJECTIVE: This study evaluated the effect of selected psychosocial,
      health and demographic characteristics of quality of life (QOL) among patients
      treated with autologous hematopoietic stem cell transplantation (HSCT). DESIGN
      AND SETTING: This was a retrospective study at Charles University Hospital,
      Hradec Kralove. METHODS: The Czech version of the international generic European
      Quality-of-Life questionnaire (EQ-5D) was applied to evaluate QOL among patients
      with acute myeloid leukemia (AML) and malignant Hodgkins and non-Hodgkins
      lymphoma (ML). The total number of respondents was 36: 12 with AML (seven males
      and five females) and 24 with ML (11 males and 13 females). The mean age of AML
      respondents was 46 years and the mean age of ML respondents was 44.5 years.
      RESULTS: Age, smoking status and education level had statistically significant
      effects on QOL among AML respondents (p < 0.05), and age had a statistically
      significant effect on QOL among ML respondents (p < 0.05). The overall QOL among
      AML and ML respondents was generally good: the mean EQ-5D score among AML
      respondents was 71.5% and among ML respondents it was 82.7%. CONCLUSION: The QOL
      among AML and ML respondents treated with autologous HSCT was good. However,
      patients more than 50 years old, smokers and patients with lower education levels
      presented worse QOL. These findings need to be better evaluated in longitudinal
      studies, using large samples.

PMID- 18317611
TI  - Obesity among parents and children from an indigenous rural community in Mexico.

PMID- 18317612
TI  - Desmin-related restrictive cardiomyopathy.
AB  - Restrictive cardiomyopathies may have different etiologies, among which we can
      point out storage diseases by accumulation of different materials such as desmin.
      Desminopathies are uncommon diseases that progress with conduction abnormalities,
      peripheral myopathies, and ventricular dysfunction. The present report describes
      a patient with complete atrioventricular block as the initial event; he later
      developed skeletal muscle alterations and heart failure. The investigation led to
      the diagnosis of restrictive cardiomyopathy due to desmin accumulation.

PMID- 18317613
TI  - Sudden death of athletes--a new fact?

PMID- 18317614
TI  - The relevance of real-time intraoperatory echocardiogram as a guide to
      percutaneous treatment of septal defects through Amplatzer device.

PMID- 18317615
TI  - I guidelines for perioperative evaluation.

PMID- 18317617
TI  - Use of drug-eluting stents in Brazil: the CENIC (National Registry of
      Cardiovascular Interventions) registry.
AB  - BACKGROUND: Drug-eluting stents (DES) represent a major advance in the management
      of ischemic heart disease, but the extrapolation of favorable results from
      clinical trials to the real-world practice has been criticized. OBJECTIVE: To
      assess the use of DES in Brazil between 2000 and 2005. METHODS: Using the
      database of the National Registry of Cardiovascular Interventions (CENIC -
      Central Nacional de Intervencoes Cardiovasculares) of the Brazilian Society of
      Hemodynamics and Interventional Cardiology (SBHCI - Sociedade Brasileira de
      Hemodinamica e Cardiologia Intervencionista), all PCI procedures with DES
      implantation performed between 2000 and 2005 were analyzed. The groups were
      divided into the following biennia: 2000-2001(A), 2002-2003 (B), and 2004-2005
      (C), and patient's clinical and angiographic characteristics were compared, as
      well as their short-term clinical outcome. Statistical analyses were performed
      using the chi-square test or ANOVA, and p values of less than 0.05 were
      considered to be statistically significant. RESULTS: A total of 154,406 PCI
      procedures were studied, and DES was used in 10,426 (7%) interventions. A
      progressive and statistically significant increase was found in the use of DES
      during the period studied: 0.14% from 2000 to 2001, 5% from 2002 to 2003, and 14%
      from 2004 to 2005 (p < 0.0001). After 2001, there was an increase in success
      rates (96.58% in 2000-2001 (A), 99.69% in 2002-2003 (B), and 99.56% in 2004-2005
      (C), A x B with p < 0.001; B x C with p = 0.015) and a decrease in hospital
      mortality rates (1.59% in group A, 0.38% in group B, and 0.66% in group C, with p
      = 0.59 for A x B and p < 0.0001 for B x C). CONCLUSION: In Brazil, the use of
      drug-eluting stents increased significantly during recent years, resulting in
      higher success rates and lower hospital mortality.

PMID- 18317618
TI  - Evaluating the adequacy of cardiovascular risk factor control after myocardial
      revascularization surgery.
AB  - BACKGROUND: Cardiovascular risk factors (RF) for coronary artery disease (CAD)
      are responsible for the occurrence of cardiovascular events. OBJECTIVE: To
      estimate the percentage of patients submitted to myocardial revascularization
      surgery (MRS) that attains adequate control of modifiable RF at least six months
      after the surgery. METHODS: Data collection was based on the review of medical
      records and a clinical interview of 88 patients submitted to MRS between January
      and December of 2004 at a reference hospital for cardiovascular diseases. The
      patients were interviewed in the follow-up period, between six and twelve months
      after the surgical revascularization. RESULTS: Mean age was 63.1 +/- 9.9 years;
      51 patients (58%) were males, 86 (97.7%) were hypertensive, 38 (43.2%) were
      diabetic, 85 (96.6%) had hypercholesterolemia and 10 (11.4%) were smokers.
      Hypertension control (PA < 140 x 90 mmHg) was attained by 24.4% of the patients;
      cholesterol (LDL cholesterol < 100 mg/dl) and diabetes control (blood glucose
      levels < 110 mg/dl) levels were 30.6% and 31.6%, respectively. The use of
      antihypertensive drugs, hypoglycemic agents and statins, when indicated, were
      96.5%, 92.1% and 78.8%, respectively. However, only 14.8% patients had their
      blood pressure, glucose and cholesterol levels within the limits accepted as
      adequate control. CONCLUSION: Despite the frequent use of drugs to control
      hypertension, diabetes and hypercholesterolemia, a high proportion of patients
      still do not achieve the target levels of risk factor control recommended by
      current guidelines at least six months after revascularization surgery, which
      suggests there is a great potential for improvement in clinical practice.

PMID- 18317619
TI  - Preinfarction angina and in-hospital outcome of elderly patients with acute
      myocardial infarction.
AB  - BACKGROUND: Preinfarction angina (PIA) may be a marker of ischemic
      preconditioning. A decrease in infarct size, ventricular remodeling, congestive
      heart failure, cardiogenic shock or death was demonstrated in the presence of
      preinfarction angina. These findings were more evident in adults, but not in the
      elderly. OBJECTIVE: To assess the relationship between PIA and the clinical
      course of elderly patients with acute myocardial infarction (AMI). METHODS: This
      was a case-series study with a comparison group. A total of 36 patients with ST
      segment elevation AMI were included in the study and divided into two groups:
      group A (21 patients with PIA) and group B (15 patients without PIA). RESULTS:
      Mean age of the study population was 70.5 years, and there was a predominance of
      males (73%). Mean body mass index was 25.3 Kg/m2. Hypertension was present in
      77.8%, diabetes in 27.8% and dyslipidemia in 32.4%. Type-A chest pain was
      reported by 71.4% of patients, and the majority of them (72.2%) were in Killip
      class I. Clinical endpoints for groups A and B were as follows: postinfarction
      angina 9.5% versus 20%, p = 0.630; heart failure 23.8% versus 13.3%, p = 0.674;
      urgent revascularization 4.8% versus 6.7%, p = 1; and cardiac arrhythmia 0%
      versus 6.7%, p = 0.417. There was no case of reinfarction, cardiogenic shock or
      death within 30 days of follow up in either group. CONCLUSION: In this case
      series, preinfarction angina was not associated with better clinical course in
      elderly patients with AMI.

PMID- 18317620
TI  - Predictive value of myeloperoxidase to identify high risk patients admitted to
      the hospital with acute chest pain.
AB  - BACKGROUND: Myeloperoxidase (MPO) is a highly expressed enzyme due to leukocyte
      activation, with multiple atherogenic actions, including LDL cholesterol
      oxidation, and is related to the instability of atherosclerotic plaque. It is a
      predictor of adverse events in healthy individuals, patients with heart disease
      or those undergoing chest pain investigations. OBJECTIVE: To analyze the
      contribution of MPO to identify patients with acute chest pain, non-ST elevation
      ECG and at high risk for in-hospital adverse events. METHODS: Patients presenting
      acute chest pain and a non-ST elevation ECG, were admitted to the hospital and
      submitted to serum MPO level measurements and a structured examination protocol.
      RESULTS: From a cohort of 140 patients, 49 (35%) were diagnosed with acute
      coronary syndrome, of which 13 patients (9.3%) were diagnosed with non-ST
      elevation acute myocardial infarction (AMI) (troponin I >1.0 ng/mL). The best MPO
      cut-off point for AMI was identified as >100 pM using the ROC curve (AUC=0.662;
      CI 95%=0.532-0.793) revealing elevated sensitivity (92.3%) and negative
      predictive value (98.1%), however with low specificity (40.2%). In the
      multivariate analysis, MPO proved to be the only independent variable to diagnose
      AMI in evolution, with an odds ratio of 8.04 (p=0.048). CONCLUSION: In patients
      with acute chest pain and no ST elevation, high MPO levels upon admission to the
      hospital are an important tool to predict in-hospital adverse events, with an
      odds ratio of eight for the diagnosis of AMI.

PMID- 18317621
TI  - Myocardial dysfunction in chagasic patients with no apparent heart disease.
AB  - BACKGROUND: The Tei index simultaneously evaluates the ventricular systolic and
      diastolic functions. It has a good correlation with hemodynamic data and has
      enabled the detection of initial ventricular function alterations of different
      etiologies. OBJECTIVE: To study initial biventricular function alterations in
      chagasic patients with no apparent heart disease, using the Tei index. METHODS:
      Forty eight individuals were evaluated. Group 1 was comprised of 25 patients
      diagnosed with Chagas' disease with no apparent heart disease and normal
      echocardiogram; group 2 was comprised of 23 healthy individuals with negative
      serological tests for Chagas' disease. RESULTS: The Tei index was significantly
      higher in the group of chagasic patients with no apparent heart disease when
      compared to that of the control group: left ventricular Tei index (0.48 +/-0.11
      vs. 0.36 +/- 0.06, p < 0.001) , right ventricular Tei index (0.34 +/- 0.10 vs.
      0.26 +/- 0.07, p = 0.001). The left and right ventricular Tei indexes were
      considered abnormal in 48% and 28% of the chagasic patients, respectively.
      CONCLUSION: Chagasic patients with no apparent heart disease present early
      alterations of the right and left ventricles.

PMID- 18317622
TI  - Treadmill stress test in children and adolescents: higher tolerance on exertion
      with ramp protocol.
AB  - OBJECTIVE: Compare exercise tolerance by children and adolescents submitted to
      treadmill stress test (TST) following Bruce Protocol (BP) or Ramp Protocol (RP),
      as well as describe velocity and inclination reached with ramp protocol to help
      set protocol exercise standards. METHODS: Observational, case-based study, with
      history control of 1,006 children and adolescents in the 4 to 17-year-old range
      who were submitted to TST between October, 1986 and February, 2003, and who
      concluded one of the two protocols. Those who interrupted their ET for other
      reasons rather than physical exhaustion, those on medication that interfered in
      HR and those with physical constraints to exercise were excluded. Statistical
      analysis of data considered p<0.05 as significance level; with confidence
      interval at 95%. RESULTS: Exercise time close to 10 minutes in RP was
      significantly higher than in BP. HR max reached was higher than 180 bpm in both
      protocols. Inclination showed to be slightly higher in younger girls in Bruce
      Protocol. Velocity and VO2 max showed to be higher for all age ranges for those
      in the Ramp Protocol. CONCLUSION: Velocity and inclination reached with ramp
      protocol may be used as reference to help set ramp protocol exercise, which
      showed superior on exertion tolerance as compared to Bruce protocol.

PMID- 18317623
TI  - Spironolactone effects on myocardium changes induced by thyroid hormone in rats.
AB  - BACKGROUND: To study the possible role of aldosterone on thyroid hormone-induced
      myocardium hypertrophy, using spironolactone. OBJECTIVE: To evaluate
      morphological changes in the myocardium induced by thyroid hormone and the
      possible effects of spironolactone use on these alterations. METHODS: Forty
      Wistar rats were studied. The animals were allocated to four groups and were
      given: the vehicle used for dilution of the thyroid hormone (C); sodium
      levothyroxin at 50 microg/rat/day (H); spironolactone, 0.3 mg/kg/day (S); or
      thyroid hormone plus spironolactone (HS), at the same doses mentioned above, for
      28 consecutive days. All the animals were weighed, had blood drawn for hormonal
      measurements and underwent ECG at the start and the end of the experiment. At the
      end of experiment all animals were euthanized, the weight of the left ventricle
      (LV) was determined and LV slices were obtained for morphological analysis.
      RESULTS: There was an increase in T3 levels, decrease of body weight and higher
      heart rate in the animals from group H. The LV weight was significantly higher in
      the H e HS groups. The histometric analyses that measured the diameter of the
      myocytes showed higher values in group H and a progressive decrease in groups HS,
      S and C, with a significant difference among all the groups. The addition of
      spironolactone decreased the transversal myocyte hypertrophy by 14.6%.
      CONCLUSION: Rats treated with thyroid hormone present cardiac hypertrophy with
      increased LV weight and greater myocyte diameter. Spironolactone, when associated
      with thyroid hormone, can partially prevent this hypertrophy through mechanisms
      that are yet to be determined.

PMID- 18317624
TI  - Sedative and cardiovascular effects of midazolam and diazepam alone or combined
      with clonidine in patients undergoing hemodynamic studies for suspected coronary
      artery disease.
AB  - BACKGROUND: Sedation during coronary angiography has been rarely studied, and it
      is important to know which drug is the best to sedate these patients. OBJECTIVE:
      To evaluate the quality of sedation and the effects of midazolam and diazepam
      alone or combined with clonidine on the heart rate (HR) and blood pressure (BP)
      of patients with suspected coronary artery disease. METHODS: This is a
      controlled, randomized, double-blind, prospective clinical study of 160 patients
      divided into five groups of 32 patients each, according to the drug used: group C
      (clonidine 0.5 microg/kg); group M (midazolam 40 microg/kg); group MC
      (combination of midazolam 40 microg/kg and clonidine 0.5 microg/kg); group D
      (diazepam 40 microg/kg); and group DC (combination of diazepam 40 microg/kg and
      clonidine 0.5 microg/kg). Sedation was evaluated based on the Ramsay scale and on
      the use of meperidine 0.04 mg.kg-1. Invasive BP monitoring, HR and the sedation
      score were analyzed every five minutes at four different time points. RESULTS:
      Patients who received midazolam presented higher sedation scores as well as HR
      and BP variation (p < 0.05). Those who received diazepam or clonidine had lower
      sedation scores, which were more satisfactory for the performance of the
      procedure, and presented a lower BP and HR variation (p > 0.05). CONCLUSION:
      Midazolam was associated with a greater sedative and cardiovascular effect,
      whereas for diazepam these effects were less intense. Clonidine and diazepam had
      similar effects on BP, HR and sedation.

PMID- 18317625
TI  - [Impact of weight loss on adipocytokines, C-reactive protein and insulin
      sensitivity in hypertensive women with central obesity].
AB  - OBJECTIVE: To assess the impact of weight reduction on serum adipocytokines, C
      reactive protein (CRP), and insulin sensitivity in hypertensive female patients
      with central obesity. METHODS: This study was performed using the database and
      stored serum samples of female patients who had participated in an intervention
      study focused on weight loss. Thirty hypertensive women aged 18 to 65, body mass
      index (BMI) > 27 kg/m2, and central obesity were selected. They were randomly
      assigned to receive either a low-calorie diet plus orlistat 120 mg three times
      daily or a low-calorie diet alone for 16 weeks. Patients who experienced weight
      loss greater than 5% (n = 24) were assessed for blood pressure, anthropometric
      parameters, visceral fat, insulin resistance (HOMA-R - homeostasis model
      assessment of insulin resistance) and sensitivity (ISI - Insulin Sensitivity
      Index) indices, plus serum lipids, adipocytokines (adiponectin, leptin, IL-6, and
      TNF-alpha) and CRP levels. RESULTS: After BMI had been reduced by approximately
      5% in both groups, visceral fat, fasting glucose, triglycerides, and TNF-alpha
      decreased. Only the orlistat group, which was more insulin resistant at baseline,
      showed a significant reduction in blood glucose after oral glucose load, in
      addition to increased insulin sensitivity. CONCLUSION: This study's findings
      indicate that a weight loss greater than 5% is associated with improved
      inflammatory status and decreased insulin resistance, regardless of changes in
      adiponectin and TNF-a levels. The greatest improvements in insulin sensitivity
      experienced by the orlistat-treated patients could not be attributed to the use
      of this drug because of the higher number of insulin-resistant subjects in this
      group.

PMID- 18317626
TI  - Systemic hypertension and microalbuminuria.
AB  - OBJECTIVE: To identify the prevalence of microalbuminuria and target organ
      lesions and their association in a hypertensive population undergoing treatment.
      METHODS: This observational, descriptive and cross-sectional study was conducted
      between April and August 2006, and included 153 hypertensive patients undergoing
      treatment at the Internal Medicine and Cardiology Outpatient Clinics at a
      University Hospital in the Southern Region of Brazil. RESULTS: The prevalence of
      microalbuminuria was 13.7% (21/153). The clinical and demographic characteristics
      of groups with and without microalbuminuria were similar. The prevalence of
      target organ lesions was 48.4%, of which most were cardiac lesions. Target organ
      lesions were found more often in the microalbuminuria group [76.2% (16/21) versus
      43.9% (58/132)] with a significant statistical difference (p=0.006). This was
      also observed in the cardiac lesions, for both the total population (p=0.003) and
      the geriatric group (p=0.006). CONCLUSION: The prevalence of microalbuminuria in
      the study population was 13.7% and that of target organ lesions was 48.4%; a
      statistically significant association was found. Microalbuminuria is also
      associated with cardiac lesions, including in the geriatric population.

PMID- 18317627
TI  - Caso 6/2007: Early post-operative cardiogenic shock after stenting of thoracic
      aorta aneurysm.

PMID- 18317628
TI  - Renin-angiotensin system: is it possible to identify hypertension susceptibility
      genes?

PMID- 18317630
TI  - Broken-heart syndrome (Takotsubo syndrome).
AB  - Stress-induced cardiomyopathy, also know as reversible left ventricular apical
      ballooning, " Broken-Heart" syndrome, and in Japan, Takotsubo, is characterized
      by the presence of a transient left ventricular dyskinetic movement of the
      anterior wall of with hypercontraction of the ventricular basilar segments
      precipitated by emotional stress. The clinical course of Takotsubo cardiomyopathy
      is similar to that of an acute myocardial infarct with typical chest pain and
      electrocardiographic changes, and during the acute phase, coronary angiography is
      used to distinguish between the two conditions.

PMID- 18317631
TI  - What the cardiologist should know about trans fats.

PMID- 18317632
TI  - Angiographic follow-up of myocardial revascularization using the vineberg
      procedure correlated with intraoperative imaging.

PMID- 18317634
TI  - Prognostic value of Tc-99m tetrofosmin myocardial perfusion gated SPECT in
      patients with diabetes mellitus and suspected coronary artery disease.
AB  - BACKGROUND: The cardiovascular disease is the main cause of death among diabetic
      patients, which makes it crucial to identify the individuals at higher risk of
      cardiovascular events. OBJECTIVE: To evaluate the prognostic value of
      scintigraphy with gated single photon emission computed tomography (SPECT) in
      patients with diabetes mellitus (DM) and suspected coronary artery disease.
      METHODS: Retrospective study with 232 diabetic patients submitted to scintigraphy
      with gated SPECT. Perfusion Gated SPECT (scores and number of altered segments)
      as well as ventricular function parameters (ejection fraction, left ventricle
      (LV) volume and contractility) were evaluated. Cardiac death, acute ischemic
      coronary syndrome, revascularization procedures or encephalic vascular accident
      were considered future cardiovascular events. The uni- and multivariate analyses
      were carried out by the multiple logistic regression model (p< 0.05). RESULTS: At
      the univariate analysis, age (p=0.02), chest angina (p=0.01), insulin therapy
      (p=0.02), myocardial perfusion abnormalities (p<0.0001), the number of segments
      involved (p=0.0001), the perfusion scores (p=0.0001), the ejection fraction
      (p=0.004), the final systolic volume (p=0.03) and the finding of segmental
      alteration at the left ventricle contractility (p<0.0001) were associated with
      future events at the univariate analysis. At the multivariate analysis, the male
      sex (p=0.007), age (p=0.03), angina (p=0.001), insulin therapy (p=0.007) and the
      SDS > 3 (p=0.0001) and the number of altered segments > 3 (p=0.0001) were
      predictors of cardiovascular events. CONCLUSION: The myocardial scintigraphy with
      gated SPECT adds independent information to the stratification of the risk of
      future cardiovascular events in patients with DM and suspected coronary artery
      disease.

PMID- 18317635
TI  - AIDS in childhood: cardiac involvement with and without triple combination
      antiretroviral therapy.
AB  - OBJECTIVE: To describe the prevalence of cardiac abnormalities in the
      echocardiogram of children with AIDS followed up in a reference service at 18+/-6
      months of AIDS confirmed diagnosis. METHODS: A cross-section study with a cohort
      after 18+/-6 months of AIDS diagnosis. The study included a total of 93 children
      with a confirmed diagnosis of AIDS with vertical transmission, with no
      malignancies and who underwent echocardiogram (echo) during cardiologic
      evaluation. Cardiac abnormalities were assessed in patients who were not treated
      (G1) and patients who were treated (G2) with combination antiretroviral therapy.
      RESULTS: When diagnosed with AIDS, the children were on average 3.07 years old
      and 50.50% were female. The combination regimen with antiretroviral agents was
      used by 47 patients (G2). Cardiac involvement was present in 40 children
      (43.00%). The presence of left ventricular dysfunction (G1: 39.10%; G2: 10.60%)
      and the isolated enlargement of left ventricle (G1: 6.60%; G2: 14.90%) were the
      most frequent findings. We observed a significant association between the groups
      without and with combination antiretroviral therapy asregards the presence of
      left ventricular dysfunction (PR= 3.42; [1.41-8.26]; p = 0.02) and malnutrition
      (PR = 1.79; [1.00-3.20]; p = 0.04). CONCLUSION: Cardiac involvement was frequent
      in children with AIDS and left ventricular dysfunction was the most common
      abnormality on echocardiogram. There was a statistically significant difference
      between the groups with and without triple combination treatment as regards the
      presence of left ventricular dysfunction and malnutrition.

PMID- 18317636
TI  - Surgical myocardial revascularization: off-pump use of bilateral internal
      thoracic artery grafting.
AB  - BACKGROUND: Advances in surgical myocardial revascularization (MR) have
      introduced additional benefits with the off-pump (OP) technique and the use of
      bilateral internal thoracic artery (ITA) grafting. Off-pump surgical MR has been
      associated with improved immediate outcomes and reduced incidence of
      perioperative complications, and the use of bilateral ITA grafts provides
      increased survival and decreased cardiovascular events in the long term.
      OBJECTIVE: To present the initial experience with the combined use of these
      advances in surgical MR. METHODS: A total of 35 consecutive patients undergoing
      off-pump MR with bilateral ITA grafting were studied; the left ITA was directed
      toward the anterior descending artery and the right ITA was anastomosed to the
      circumflex artery branches. The predominant comorbidities were previous
      myocardial infarction in 71.4% of the patients, diabetes mellitus in 34.2%, and
      renal failure in 14.2%. RESULTS No patients presented electrocardiographic
      changes or enzyme elevation in the postoperative period. The number of bypasses
      per patient ranged from two to four (median of three bypasses/patient).
      Postoperative hospital stay ranged from three to 12 days (mean of 4.7 + 1.7
      days). No cases of sternal dehiscence or infection were observed, but one patient
      suffered a stroke on the fourth postoperative day and died. Late follow-up lasted
      from four to 48 months. No late deaths occurred, 31 patients are asymptomatic,
      and three have residual angina. CONCLUSION: The combination of these technical
      advances in surgical myocardial revascularization proved efficient and able to
      contribute to improved benefits in the long term.

PMID- 18317637
TI  - Lipid profile and intensity of atherosclerosis disease in acute coronary
      syndrome.
AB  - BACKGROUND: The relationship between coronary artery disease (CAD) and
      dyslipidemia in acute coronary syndromes has been rarely demonstrated in clinical
      and epidemiological studies. OBJECTIVE: To evaluate the association between lipid
      profile and severity of CAD in patients with acute coronary syndrome without ST
      segment elevation. METHODS: In this retrospective study, the authors reviewed
      medical records of 107 consecutive patients diagnosed with acute coronary
      syndrome (ACS) without ST-segment elevation admitted within a one-year period and
      who had undergone coronary angiography during hospitalization. Laboratory
      evaluation included serum levels of lipid fractions. Severity of CAD was
      determined by evaluating the number, degree, and score of coronary artery
      obstructions. For statistical analysis, the Students t test, chi-square test and
      ANOVA with statistical significance set at p<0.05, as well as multivariate
      analysis were performed. RESULTS: A total of 107 patients were included; 94(88%)
      had CAD, of which 50 (53.2%) were males with predominance of multivessel disease.
      As regards the lipid profile, 64(59.8%) patients were observed to have
      TC<200mg/dl, 33(30.8%) had HDL<40 mg/dl, and 38(35.5%) had LDL<100mg/dl. The
      analysis of coronary angiographies showed that 94(88%) patients had CAD, and 84%
      had > 70% stenosis. In the association between lipid profile and CAD, we observed
      a higher TC/HDL ratio in the multivessel and two-vessel groups in comparison with
      the one-vessel group (4.3+/-2, 4.0+/-1.7, 2.9+/-1.6, respectively) with ANOVA
      p=0.049. In the multivariate analysis, the TC/HDL ratio remained a significant
      predictor (p = 0.016). CONCLUSION: The TC/HDL ratio was a marker of severity of
      CAD in relation to the number of vessels affected, thus demonstrating that the
      lipid profile can be a determinant of severity in patients with ACS without ST
      segment elevation.

PMID- 18317638
TI  - An assessment of neutrophils/lymphocytes ratio in patients suspected of acute
      coronary syndrome.
AB  - BACKGROUND: Leukocytes total count is an independent risk marker for
      cardiovascular events. The ratio between neutrophils and lymphocytes (N/L) count
      has been investigated as a new predictor for cardiovascular risk, although its
      diagnostic role when assessing patients suspected of an acute coronary syndrome
      (ACS) condition is not yet known. OBJECTIVE: To evaluate the diagnostic power of
      N/L ratio in patients who have been admitted at a Chest Pain Unit (CPU) with the
      suspicion of ACS. METHODS: Evaluation was conducted in 178 patients admitted with
      chest pain. Diagnostic flowchart including clinical, electrocardiographic, and
      laboratory data. Diagnosis obtained was: acute myocardial infarction (AMI) with
      (AMI-STE) and with no segment T elevation (AMI-NSTE), unstable angina (UA ) and
      non-cardiac pain (NC). Total and differential leukocyte count was conducted in
      peripheral blood sample collected at admission. RESULTS: Patients diagnosed with
      non-cardiac pain reported the lowest N/L ratio (n=45; 3.0 +/- 1.6), followed by
      UA (n=65; 3.6 +/- 2.9), AMI-NSTE (n=33; 4.8 +/- 3.7) and AMI-STE (n=35; 6.9 +/-
      5.7); p < 0.0001. N/L ratio above 5.7 (highest quartile) reported 91.1%
      specificity, 4.51 odds ratio (CI 95% 1.51 to 13.45) for the final diagnosis of
      ACS when compared to the groups at lower quartiles. CONCLUSION: The N/L ratio
      presents correlation with final diagnosis of patients with suspicion of ACS at
      admission. Considering this is a low cost, good reproductibility test, new
      studies should ellucidate whether the ratio may be of relevance for diagnosis
      flowcharts currently in use.

PMID- 18317639
TI  - Internal thoracic artery graft (ITAG): patency and functional status at rest and
      during dobutamine-stress echocardiography.
AB  - BACKGROUND: The patent internal thoracic artery graft (ITAG) usually has a
      diastolic fraction (DF) > 50% of the flow. The functional assessment can be
      evaluated by the coronary reserve index (CRI). OBJECTIVE: The objective was to
      evaluate the patency and functional status of the ITAG through echocardiography
      and Doppler. METHODS: Data from sixty-six patients who underwent dobutamine
      stress echocardiography (DSE) were prospectively collected and analyzed. Group I
      (GI) had 49 ITAG without stenosis, Group II (GII), 10 ITAG with significant
      stenosis (> 50% and <100%) and Group III (GIII) had 7 ITAG with total occlusion.
      Diameters and Doppler spectrums from the ITAG at rest and during DSE were
      evaluated. RESULTS: Considering patency a DF >50%, it was observed in 49 ITAG
      (GI= 40, GII= 8 and GIII= 1) at rest and in 61 ITAG (GI=49, GII=10 and GIII=2)
      during DSE. The sensitivity, specificity, positive predictive value (PPV),
      negative predictive value (NPV) and accuracy were respectively, 81%, 86%, 98%,
      35% and 82%, and 100%, at rest and 71%, 97%, 100% and 97% in the DSE. The ITAG
      with DF>50% at rest were patent and the ones with DF<50% in the DSE presented
      total occlusion. Considering a CRI>1.8 for a good functional status, it was
      observed in 42 ITAG (39 from GI, 2 from GII and 1 from GIII), determining
      sensitivity=79%, specificity=85.7%, PPV=94%, NPV=59% and accuracy= 80.9%. The CRI
      in GI was higher (p= 0.02) than in GII or GIII. CONCLUSION: In our study, the non
      invasive assessment of the ITAG was effective to verify the patency and the
      functional status.

PMID- 18317640
TI  - Revision of the Sokolow-Lyon-Rappaport and cornell voltage criteria for left
      ventricular hypertrophy.
AB  - BACKGROUND: Electrocardiographically-detected left ventricular hypertrophy (LVH)
      is a strong predictor of cardiovascular morbidity and mortality. OBJECTIVE: To
      assess the performance of the Sokolow-Lyon-Rappaport (SLR) and Cornell voltage
      criteria in a population sample regarding the diagnosis of LVH on echocardiogram
      (ECHO). METHODS: A total of 641 out of the 682 participants of the second phase
      of the MONICA-Vitoria project were assessed using electrocardiogram and
      echocardiogram. A subgroup of healthy individuals (n=269) was used to generate
      reference values of LV mass (LVM). Sensitivities and specificities of the
      electrocardiographic criteria were determined by the ROC (receptor-operator
      characteristics) curve in relation to the diagnosis of LVH, as defined by the
      internal echocardiographic criterion (LVM > 48 and 46 g/m2.7 for males and
      females, respectively). RESULTS: The prevalence of LVH as detected by ECHO was
      23.7% in the total sample, in which 49% of the individuals were hypertensive. The
      Cornell criterion showed a better association with the LVM as estimated by ECHO
      (r= 0.37, p < 0.01) than the SLR criterion (r= 0.19) as well as a better
      performance in the analysis of the area under the ROC curve. The new cut-off
      points for the internally-defined Cornell voltage criterion (2.3 mV for males and
      1.9 mV for females) showed an acceptable combination of sensitivity (22.5 and 28%
      for males and females, respectively), with a high specificity (95%). CONCLUSION:
      The classic SLR and Cornell voltage criteria showed a low performance in relation
      to LVH as detected by the ECHO. However, this accuracy may be improved by using
      the Cornell voltage criteria defined in the present study.

PMID- 18317641
TI  - The importance of the interaction between leukocyte integrin Mac-1 and platelet
      glycoprotein Ib-a for leukocyte recruitment by platelets and for the inflammatory
      response to vascular injury.
AB  - OBJECTIVE: To assess the importance of the interaction between leukocyte integrin
      Mac-1 (a Mb 2) and platelet glycoprotein (GP) Ib-a for leukocyte recruitment
      after vascular injury and the effect of the neutralization of the Mac-1-GPIba
      interaction on cell proliferation and the neointimal hyperplasia triggered by the
      vascular injury. METHODS: A peptide called M2 or anti-M2 antibody was developed
      to block the Mac-1-GPIba interaction. This peptide was injected and compared to a
      control-peptide in C57B1/6J mice submitted to vascular injury of the femoral
      artery with a guide wire. One, five or 28 days after the vascular injury, the
      femoral arteries were removed for morphometric and immunohistochemical analyses.
      RESULTS: The blocking of the Mac-1-GPIba interaction promoted a statistically
      significant reduction in the number of leukocytes in the neointimal layer on the
      first day after the vascular injury (control: 7.9+/-5.0% of the cell total versus
      anti-M2: 2.0+/-1.6%, p=0.021), as well as determined a statistically significant
      decrease in leukocyte accumulation in the neointimal layer on days 5 and 28
      (control: 42.3+/-12.9% versus anti-M2: 24.6+/-10.8%, p=0.047 and control: 7.9+/
      3.0% versus anti-M2: 3.3+/-1.3%, p=0.012; respectively). Cell proliferation in
      the neointimal layer of the vessel five days post-injury was reduced with the
      blocking of the Mac-1-GPIba interaction (control: 5.0+/-2.9% of the cell total
      versus anti-M2: 1.8+/-0.5%; p=0.043), along with a significant decrease in cell
      proliferation in the vessel neointimal layer 28 days post-injury (control: 3.8+/
      1.7% versus anti-M2: 2.0+/-1.2%; p=0.047). The blocking of the Mac-1-GPIba
      interaction also determined a statistically significant decrease of the intimal
      thickening 28 days post-injury (control: 10,395+/-3,549 microm(2) versus anti-M2:
      4,561+/-4,915 microm(2); p=0.012). CONCLUSION: Leukocyte recruitment after a
      vascular injury depends on the Mac-1-GPIba interaction and the neutralization of
      this interaction inhibits cell proliferation and neointimal formation.

PMID- 18317642
TI  - Case 01/2008: a young female patient with the familial form of hypertrophic
      cardiomyopathy, who evolved with syncope, complex ventricular arrhythmia and
      cardiogenic shock.

PMID- 18317644
TI  - [Pelvic exenteration and treatment of cancer of the rectum].

PMID- 18317645
TI  - [Pelvic exenteration for T4 rectal cancer: a series of 15 ressectable cases].
AB  - BACKGROUND: Pelvic exenteration is the best therapeutic choice for treatment of
      T4 rectal cancer. Although, this operation still presents considerable mortality
      and high morbidity. AIM: To report on a series of 15 patients with a T4 rectal
      cancer at a general hospital and describe the outcomes (morbidity, mortality and
      long-term survival) following pelvic exenteration. METHODS: Complete follow-up
      data were available on 15 patients who underwent pelvic exenteration for T4
      rectal cancer between 1998 and 2006. These subjects comprised seven men and eight
      women with a mean age of 65 years. All of them presented serious incapacitating
      complaints. The surgical procedures included: infraelevator exenteration (n = 6),
      supraelevator exenteration (n = 4), posterior exenteration (n = 3) and, posterior
      exenteration plus partial cystectomy and ureterectomy (n = 2). RESULTS: The mean
      duration of surgery was 403 minutes (280-485). The mean blood loss was 1620 mL
      (300-4.800). The postoperative mortality was 6,66% (n = 1). The overall rate
      morbidity was 53,3% (n = 8). The pathological examination showed that all
      resections were R0. Lymph node involvement was present in four patients (26,66
      %), and all of them died due to tumor recurrence. The overall 5-year survival
      rate was 35,7%. CONCLUSION: In spite of its aggressive nature and high morbidity,
      pelvic exenteration seems justified in rectal carcinoma when the disease extends
      to the urinary or genital tract. This procedure may offer long-term disease
      control.

PMID- 18317646
TI  - [Compliance to drug therapy in inflammatory bowel diseases outpatients from a
      university hospital].
AB  - BACKGROUND: Compliance to drug therapy is important for a successful treatment.
      Although many studies have assessed compliance to treatment in patients with
      chronic diseases, few investigations have been carried out in inflammatory bowel
      diseases. AIM: To assess compliance to drug therapy in patients with inflammatory
      bowel diseases, Crohn's disease and ulcerative colitis, followed at a university
      hospital, who had prescribed medication supplied by the Brazilian National Health
      System. METHODS: In a cross sectional study, a structured interview was applied
      to assess the compliance of 26 Crohn's disease patients, 26 ulcerative colitis
      patients and 4 cases with undetermined colitis. Patients were characterized as
      presenting higher or lower degree of compliance, based on the comparison of the
      information provided by the patient in the interview and data in the medical
      records. The Morisky test was also used to assess the behavioral pattern of the
      patient regarding the daily use of the medication. RESULTS: The interview showed
      that 15.4% of patients with Crohn's disease and 13.3% of those with ulcerative
      colitis could be regarded as less compliant. However, the Morisky test revealed
      lower compliance in 50% of patients with Crohn's disease and 63.3% of those with
      ulcerative colitis. Univariate analysis showed an association between low
      compliance and long disease duration, married status and colon involvement in
      Crohn's disease, and between low compliance and increased disease activity and
      greater number of medications in ulcerative colitis. However, multivariate
      analysis did not confirm any association between low compliance and any
      demographic or clinical factor. CONCLUSIONS: A high degree of noncompliance to
      treatment, linked to habitual behavior and hard to predict from demographic or
      clinical factor, was detected in inflammatory bowel disease patients, which
      suggests the need for investment in patient education regarding medication use.

PMID- 18317647
TI  - Viscosities reproductive patterns for use in videofluoroscopy and rehabilitation
      therapy of dysphagic patients.
AB  - BACKGROUND: Usually the suitable consistence identified and indicated as safe by
      videofluoroscopic method has been empirically obtained by association of barium
      sulfate solution with meals. However, it has been evidenced to be very difficult
      to reproduce this consistence in nutritional rehabilitation therapy from
      subjective information. AIM: To build two reproductive similar crescent
      viscosities series of solutions, with and without barium sulfate, to be used, the
      first, as radiological contrasted mean and the second, as base to reproduce the
      defined safer consistence, in the oral diet rehabilitation of dysphagic patients.
      METHODS: Two viscosity solutions series were obtained from starch and distilled
      water with and without 100% barium sulfate solution. The viscosity levels were
      defined step by step with digital viscosimeter (Brookfield, model LVTD-II) and
      with infrared thermometer Icel TD - 960. The fluids viscosity was register in
      centipoises, with their inferior and superior values followed by complimentary
      information about spindle kind, rotation speed and temperature. RESULTS: The two
      series of solutions, with and without barium sulfate, could be defined as aqueous
      (>1-143,5 cP), fine liquid (428 - 551 cP), thick liquid (4.284 -7.346,5 cP)),
      pasty (7.346,4 - 13.035 cP), pasty thick (19.260 - 34.320 cP) and creamy (163.500
      - 255.300 cP). CONCLUSION: The study could offer reproductive formulas, with and
      without contrast mean, to be follow for obtaining the desirable viscosity to be
      used, each of them, in radiological evaluation and in nutritional diet minimizing
      the gaps fails between evaluation and therapy.

PMID- 18317648
TI  - p53 and Ki-67 in Barrett's carcinoma: is there any value to predict recurrence
      after circumferential endoscopic mucosal resection?
AB  - BACKGROUND: There are situations in which the specimens obtained after endoscopic
      mucosal resection of superficial adenocarcinoma arising from Barrett's esophagus
      are not adequate for histopathological assessment of the margins. In these cases,
      immunohistochemistry might be an useful tool for predicting cancer recurrence.
      AIM: To evaluate the value of p53 and Ki-67 immunohistochemistry in predicting
      the cancer recurrence in patients with Barrett's esophagus-related cancer
      referred to circumferential endoscopic mucosal resection. METHODS: Mucosectomy
      specimens from 41 patients were analyzed. All endoscopic biopsies prior to
      endoscopic mucosal resection presented high-grade dysplasia and cancer was
      detected in 23 of them. Positive reactions were considered the intense coloration
      in the nuclei of at least 90% of the cells in each high-power magnification
      field, and immunostaining could be classified as superficial or diffuse according
      to the mucosal distribution of the stained nuclei. RESULTS: Endoscopic mucosal
      resection samples detected cancer in 21 cases. In these cases, p53
      immunohistochemistry revealed a diffuse positivity for the great majority of
      these cancers (90.5% vs. 20%), and Ki-67 showed a diffuse pattern for all cases
      (100% vs. 30%); conversely, patients without cancer revealed a superficial or
      negative pattern for p53 (80% vs. 9.5%) and Ki-67 (70% vs. 0%). During a mean
      follow-up of 31.6 months, 5 (12.2%) patients developed six episodes of recurrent
      cancer. Endoscopic mucosal resection specimens did not show any significant
      difference in the p53 and Ki-67 expression for patients developing cancer after
      endoscopic treatment. CONCLUSIONS: p53 and Ki-67 immunohistochemistry were useful
      to confirm the cancer; however, they had not value for predicting the recurrent
      carcinoma after circumferential endoscopic mucosal resection of Barrett's
      carcinoma.

PMID- 18317649
TI  - [Esophagitis in patients with acquired human immunodeficiency syndrome: an
      histological and immunohistochemistry study].
AB  - BACKGROUND: Almost all patients with acquired immunodeficiency virus syndrome
      will have gastrointestinal symptoms during the course of their illness. The high
      prevalence and complications of esophagitis are well documented. AIM: Graduate
      esophagitis; identify microorganisms like Candida sp, cytomegalovirus,
      herpesvirus and mycobacteria; identify by immunohistochemical staining viral
      agents cytomegalovirus, herpesvirus I, herpesvirus II, Epstein-Barr Virus, human
      papilloma virus and human immunodeficiency virus; verify how immunohistochemistry
      changes the profile of esophagitis; verify the association between the
      histological and endoscopical findings; verify the relevance of the number of
      fragments studied in the characterization of the histological agents. METHODS: We
      studied retrospectively esophageal biopsies in 227 patients with acquired
      immunodeficiency virus syndrome using hematoxylin and eosin, PAS (periodic acid
      of Schiff), Groccott and Ziehl-Nielsen stains and immunoperoxidase stains to
      detect opportunistic agents. Endoscopic aspects were studied. RESULTS: The non
      specific esophagitis grade III, in the inferior third of the esophagus, was the
      most frequent type. Candida sp was the most frequent agent, followed by viruses
      cytomegalovirus, herpesvirus and mycobacteria. The presence of plaque and
      ulceration suggested the diagnosis of esophageal candidiasis and cytomegalovirus
      esophagitis. Immunohistochemical allowed the characterization of cytomegalovirus
      and of herpesvirus in those cases where other techniques could not achieve it,
      furthermore the cytomegalovirus was also found in histological normal cases,
      making the use of this technique advisable in routine diagnosis. The herpesvirus
      I was not found isolated but associated to herpesvirus II. We have not found
      immunoreactivity for the Epstein-Barr virus and the human immunodeficiency virus.
      The number of fragments does not seem to influence the detection of the etiologic
      agent. CONCLUSION: The endoscopic findings of plaques or ulcers are associated
      with candidiasis or cytomegalovirus esophagitis. Immunohistochemisty improved the
      diagnosis of viral infections. It is possible to detect cytomegalovirus
      infections in endoscopic and histologic normal cases.

PMID- 18317650
TI  - Cytomegaloviral colitis in HIV positive patients: endoscopic findings.
AB  - BACKGROUND: Diarrhea in seropositive human immunodeficiency virus patients is one
      of the most important and disabling symptoms, and often decreases their quality
      of life. Cytomegalovirus colitis is among the principal causes of this symptom
      and colonoscopy is the gold standard examination to diagnose it. AIM: To define
      the main endoscopic findings in seropositive human immunodeficiency virus
      patients with cytomegalovirus colitis. METHODS: Two hundred and forty-three
      colonoscopies were performed in 200 seropositive human immunodeficiency virus
      patients with diarrhea associated or not to abdominal pain or gastrointestinal
      bleeding, over 10-year period, whom 51 patients were diagnosed with
      cytomegalovirus colitis. Full length colonoscopy with ileum intubation was always
      tried and multiple biopsies of all segments examined, including endoscopically
      normal segments, were attempted. All diagnoses were confirmed by histologic and
      immunohistochemical studies. RESULTS: Total colonoscopy was possible in 98.03%
      and ileum intubation in 88.23% of these cytomegalovirus colitis patients. At
      colonoscopy, a heterogeneous ulcerative pattern was presented in 72.54%, an
      inflammatory process of the mucosa in 21.56% and 5.88% of the patients mucosa was
      endoscopically normal. CONCLUSION: Full length colonoscopy with ileum intubation
      and multiples biopsies of all segments, even when they are endoscopically normal,
      have always to be attempted in cases of seropositive human immunodeficiency virus
      patient with diarrhea.

PMID- 18317651
TI  - [Prevalence reduction of duodenal ulcer: a Brazilian study. (retrospective
      analysis in the last decade: 1996-2005)].
AB  - BACKGROUND: The duodenal ulcer always represented a very prevalent pathology
      among the gastrointestinal tract diseases worldwide. The average prevalence is
      approximately 10% of the world population. In the 90s the literature (both
      European and North American) begin to show a crescent reduction of this
      prevalence in many countries. AIM: To show through a retrospective analysis the
      annual prevalence of the duodenal ulcer in the last 10 years in a Digestive
      Endoscopy Service which is referred to public medical system in Porto Alegre and
      its suburban area and countryside of the State of Rio Grande do Sul, Brazil. The
      data analyzed is from March 1996 to December 2005. Specific data: transversal
      retrospective study with documented analysis of endoscopic diagnosis of upper
      gastrointestinal endoscopy. METHODS: A retrospective analysis of the diagnosis of
      the 13.130 procedures of upper gastrointestinal endoscopy between 1996 and 2005.
      The Sakita classification was used to verify the duodenal ulcer activity taking
      into consideration the patients who have lesions on A1 to S1 levels. To verify if
      there was a statistical significant results, a linear regression test was done
      (linear regression model). RESULTS: A graduate decrease of the prevalence
      percentuals was observed, year after year, it began with 8.3% of prevalence in
      1996 and finished with 3.3% in the beginning of 2006. The average annual
      reduction of this prevalence was calculated following the regression test and it
      was placed in the 1.3% a year in the studied period of time. In 2003, in an
      isolated way, it was an exception in the decrease of the percentage because it
      presented a prevalence increase of (6.5%) comparing to the first 6 years of
      study. CONCLUSION: In this study it was observed a decrease of duodenal ulcer
      prevalence, 1.3% a year to be more accurate in 10 years of study, showing a
      statistical significance in the linear regression test.

PMID- 18317652
TI  - [Comparison of pre-operative exams and per-operative findings in living donor
      liver transplantation].
AB  - BACKGROUND: Success in living donor liver transplantation is associated to donor
      vascular and biliar anatomy. AIM: Compare pre-operative and per-operative
      findings in living liver donors related to portal vein, hepatic artery, bile duct
      and hepatic venous drainage anatomy. METHODS: Donors charts of living donor liver
      transplants done at Clinics Hospital of the Federal University of Parana,
      Curitiba, PR, Brazil, were reviewed between March 1998 and August 2005. On the
      pre-operative period the anatomy was analysed through: celiac and mesenteric
      arteriography of the hepatic artery and portal vein (venous phase); magnetic
      resonance imaging of the venous drainage, portal vein and bile duct. Normality
      was determined based on data of the literature. Pre-operative findings were
      compared to per-operative findings. RESULTS: Portal vein and hepatic artery were
      studied in 44 patients, 16 females and 28 males, mean age of 33 years old. In 8
      cases the left liver lobe was used to pediatric receptor, in 36 cases the right
      liver lobe was used to adult receptor. Bile duct anatomy was studied in 37 cases
      and venous drainage in 32. Over all, the findings related to pre-operative and
      per-operative anatomy were not coincident in 36.36% of the cases. In the case of
      hepatic artery, they were not coincident in 11.36%, in the case of the portal
      vein in 9.1%, in the case of the venous drainage in 9.37% and in the case of the
      bile duct in 21.6%. CONCLUSION: The pre-operative and per-operative findings
      related to vascular and bile duct donor anatomy are frequently different in
      living donor liver transplantation.

PMID- 18317653
TI  - [Descriptive analysis of the social, clinical, laboratorial and anthropometric
      profiles of inflammatory bowel disease inwards patients from the "Clementino
      Fraga Filho" University Hospital, Rio de Janeiro, RJ, Brazil].
AB  - BACKGROUND: The epidemiologic survey in Brazil is limited probably due to a
      diagnosis deficiency and a small number of population-based studies performed.
      The majority of the prevalence studies available have evaluated inflammatory
      bowel diseases outpatients, but the knowledge of the profile of inflammatory
      bowel diseases inpatients is important in order to detect predictive markers of
      disease severity that will allow earlier medical intervention decreasing the rate
      of hospitalization and reducing the Health System costs. AIM: To determine
      social, clinical, laboratorial and anthropometric profiles of hospitalized adults
      inflammatory bowel diseases patients of a tertiary university hospital. METHODS:
      Prospective study was performed with 43 inflammatory bowel diseases inpatients
      from clinical and surgical wards and emergency section of university hospital. We
      characterized demographic data, presence of comorbidities, disease location and
      behavior, surgical past-history, extra intestinal manifestations using
      standardized definitions. Laboratory results were abstracted from medical records
      and anthropometric measures were performed during our visit. RESULTS: The vast
      majority of the inflammatory bowel diseases patients had Crohn's disease (72.1%),
      with ileocolic involvement (60%), with a penetrating disease behavior (77.4%)
      while ulcerative colitis group presented mostly pancolitis (50%). Articular pain
      was the most common (44.2%) extra intestinal manifestation of inflammatory bowel
      diseases patients and 97.7% of them had at least one type of complication related
      to disease. Although, the previous use of specific medical therapies to
      inflammatory bowel diseases before the hospitalization (more frequently
      corticosteroids) was done (79%), the majority of the patients were hospitalized
      because of inflammatory bowel diseases activity. Disease activity was present in
      80.7% of Crohn's disease and 50% ulcerative colitis patients. Inflammatory bowel
      diseases mortality rate was 5.5% (2/36). Comorbidities presence occurred only in
      30.2% of inflammatory bowel diseases patients. The predominant surgery performed
      was intestinal resection. The interval between the symptoms appearance and the
      definitive diagnosis was less than 1 year in more than 70% of inflammatory bowel
      diseases patients. Laboratory findings detected were a decreased serum albumin
      (85.7%) and anemia (69.8%). The majority of the patients had at least one
      anthropometric alteration. The social stratification of the inflammatory bowel
      diseases group was similar to the Brazilian population. CONCLUSION: The
      inflammatory bowel diseases inpatients from the university hospital wards had
      more severe evolution of these illnesses with an active and extensive disease
      with complications and frequent extra intestinal manifestations, despite the
      prolonged use of corticosteroids. The higher prevalence of Crohn's disease
      inpatients than ulcerative colitis could reflect a higher aggressive behavior of
      this disease. The reduced serum albumin, anemia and anthropometric alterations
      are common inflammatory bowel diseases inpatients and could be related to a major
      severity of inflammatory bowel diseases evolution.

PMID- 18317654
TI  - [Clinical characteristics of pediatric patients with chronic constipation
      according to age group].
AB  - BACKGROUND: There was no study evaluating clinical characteristics of
      constipation according pediatric age groups. AIM: To evaluate the clinical
      characteristics of patients with chronic constipation according to age group.
      METHODS: This retrospective study evaluated the demographic data and clinical
      characteristics of pediatric patients with chronic constipation who had been
      admitted to an outpatient clinic between May 1995 and December 2000. Data was
      analyzed according to the followings age groups: infants, pre-school, school age
      and adolescent. RESULTS: Five hundred and sixty one patients were included in the
      study. The percentage of patients according to age groups were: infants (19.1%),
      pre-school (42.9%), school age (26.9%), and adolescents (11.0%). There was no
      statistical gender difference among the four age groups. Less than three bowel
      movements per week were observed more frequently in pre-school (65.8%) and school
      age (59.6%) than in infants (52.4%) and adolescents (43.1%). Fecal escape
      ("soiling") was found in 75.6% of the pre-school patients aged more than 48
      months, in 68.2% of the school age and in 76.7% of the adolescents. Soiling was
      more frequent in boys (80.7%) than in girls (50.0%) only in school age children.
      Retentive posture (67.6%, 40.7%, 27.2%), fear for defecation (70.2%, 44.2%,
      29.7%) and abdominal pain (80.8%, 69.6%, 73.6%) were observed, respectively, more
      frequently in pre-school than in school age and adolescents. CONCLUSION: There
      were differences in clinical characteristics according to age group. However,
      prolonged duration of constipation and an elevated number of complications were
      observed in all age groups, especially fecal soiling and abdominal pain.

PMID- 18317655
TI  - [Nutritional risk and malnutrition determination by anthropometry in cirrhotic
      children and adolescents].
AB  - BACKGROUND: The malnutrition is a frequent finding in adults with cirrhosis, but
      the prevalence of nutritional risk and malnutrition is little known in pediatric
      patients. AIM: To evaluate through anthropometry the presence of nutritional risk
      and malnutrition in cirrhotic pediatric patients regularly attended at the
      Pediatric Gastroenterology Service of "Hospital de Clinicas" of Porto Alegre, RS,
      Brazil. METHODS: Cross-sectional study with 42 cirrhotic children and adolescents
      aged between 3 months and 18 years. The nutritional evaluation was made by the
      determination of the weight/age, height/age, body mass index and triceps skinfold
      thickness and arm muscle circumference measurements. Patients considered in
      nutritional risk were < or = -1,28 Z score which corresponds to < or = 10th
      percentile, and those under -2,0 Z and < or = 3th percentile were in malnutrition
      status. According to Child-Pugh criteria, 22 patients were classified as A (mild
      severity), 15 (moderate) B and 5 C (intense). RESULTS: The mean weight/age,
      height/age and body mass index Z scores were, respectively, - 0,38 +/- 1,4 SD, -
      0,83 +/- 1,16 SD and 0,17 +/- 1,3 SD. Patients in nutritional risk were 3/42
      (weight/age), 8/42 (height/age), 12/37 (triceps skinfold thickness), 9/37 (arm
      muscle circumference), 2/38 (body mass index); in malnutrition status were 6/42
      (weight/age), 7/42 (height/age), 4/37 (triceps skinfold thickness) and 4/37 (arm
      muscle circumference) and 3/38 (body mass index). CONCLUSION: The prevalence of
      nutritional risk was 32.4% and chronic malnutrition was 16.7%. The index which
      better reflected the nutritional risk in these patients was triceps skinfold
      thickness. Chronic malnutrition status occurrence was greater in the height/age
      index.

PMID- 18317656
TI  - [Non alcoholic fatty liver disease: treatment with soluble fibres].
AB  - The pilot study evaluated the efficiency of oral soluble fibers to treat patients
      with nonalcoholic fatty liver disease. Twelve patients received 10 g/day of
      soluble fibers during 3 months. After the treatment 100% of patients presented
      reduction in body mass index, waist circumference and insulin resistance index.
      In 66.7% of the patients were observed reduction of the cholesterol levels and
      75% presented normal liver enzymes (AST, ALT, and GGT). The present study
      suggests that oral soluble fibers may be useful to control risk factors and liver
      enzymes in patients with nonalcoholic fatty liver disease. However, future
      studies with histological controls are considered necessary.

PMID- 18317657
TI  - [I Brazilian consensus of endoscopic ultrasonography].
AB  - BACKGROUND: In the last 20 years, several papers have focused on demonstrating
      the impact of endoscopic ultrasonography findings on the management of different
      clinical scenarios in digestive disease. This fact is an indirect evidence of the
      difficulty of popularization of the method. On other hand, the limited
      availability of endoscopic ultrasonography in Brazil is a direct evidence of this
      limitation. This was the rationale for the organization of a consensus meeting on
      endoscopic ultrasonography. It was aimed to identify the best evidence that
      support the use of endoscopic ultrasonography in gastroenterology. METHODS: A
      panel of experts on endoscopic ultrasonography was selected based on the files of
      the Gastroenterology and Endoscopy Societies and on the registries of endoscope
      manufacturers. Two members of the meeting selected the relevant topics that were
      transformed into questions. The topics and the questions were debated among the
      experts five months before the consensus meeting. The experts were asked to
      perform systematic reviews in order to answer the questions so it could be
      possible to grade the answers based on the strength of the evidence. During the
      two days of the meeting the answers were presented, debated and voted. Consensus
      was reached when a minimum of 70% of the voters were in agreement. The final
      consensus report was submitted to the experts' evaluation and approval. RESULTS:
      Seventy nine questions were debated by the experts at the pre-Consensus meeting.
      As the result of this debate 85 questions came out and were assigned to the
      members of the panel. During the Consensus meeting 22 experts debated and voted
      85 answers. Consensus was reached for several clinical scenarios for which the
      impact of endoscopic ultrasonography findings were supported by level 1
      evidences: differential diagnosis of subepithelial lesions and thickening of
      gastric folds, staging and diagnosis of unresectable esophageal cancer, indirect
      signs of peritoneal involvement of gastric cancer, MALT gastric lymphoma and
      rectal cancer staging, diagnosis of common bile duct and gallbladder stones,
      diagnosis of chronic pancreatitis and differential diagnosis of a solid mass in
      chronic pancreatitis, differential diagnosis of the pancreatic cyst, prediction
      of the results of the endoscopic treatment of esophageal varices and diagnosis
      and staging of non-small cell lung cancer. CONCLUSIONS: There are the highest
      levels of evidences that support the indication of endoscopic ultrasonography for
      several digestive diseases and even for non-small cell lung cancer.

PMID- 18317661
TI  - Field studies on the environmental factors in controlling microcystin production
      in the subtropical shallow lakes of the Yangtze River.
AB  - Microcystin (MC) problem made more and more care about in China, intercellular MC
      (Int-MC) and cellular MC (Cel-MC) were important contents to reflect the
      producing-MC ability by cyanobacteria and by lakes. To study the correlations
      between Int-MC, Cel-MC concentration and biological and environmental factors,
      eight cyanobacterial blooming lakes were studied in the middle and lower reaches
      of the Yangtze River. Microcystin-RR (MC-RR) and Microcystin-LR (MC-LR) were the
      primary toxin variants in our data. From the linear correlations between MC and
      environmental factors, cellular-YR had significant correlation with most of
      chemical factors except total nitrogen (TN) and the ratio of total nitrogen and
      total phosphorus (TN/TP), most intracellular MC analogues had significant
      correlations with total dissolved nitrogen (TDN), ammonium (NH (4) (+) ), nitrite
      (NO (2) (-) ), TP, total dissolved phosphorus (TDP), Microcystis. From the
      canonal correspondence analysis, Int-MC concentrations were closely related with
      the chemical and biological factors, such as TP, total organic carbon (TOC),
      chlorophyll a (Chl a), Microcystis biomass, et al. While Cel-MC contents,
      especially Cel-RR and Cel-LR, were closely related with light environmental in
      the lakes such as water depth and transparence.

PMID- 18317662
TI  - A ring-shaped stone in a female urethral diverticulum: case report and review of
      literature.
AB  - The classic presentation of urethra diverticula has been described historically
      as the "3 Ds," meaning dysuria, dyspareunia, and dribbling. As the symptoms are
      not specific, urethral diverticulum may often be misdiagnosed. We report a case
      of a ring-shaped stone in a female urethral diverticulum, which was successfully
      treated surgically.

PMID- 18317663
TI  - Urodynamic study and quality of life in patients with fibromyalgia and lower
      urinary tract symptoms.
AB  - The aim of this study was to evaluate clinical and urodynamic observations on
      women with fibromyalgia (FM) and lower urinary tract symptoms (LUTS). Fifty-one
      patients with FM and LUTS and 50 patients with LUTS without FM answered questions
      about urinary symptoms and also two questionnaires about quality of life
      measures: "Medical Outcomes Study 36-Item Short-Form Health Survey" and "King's
      Health Questionnaire". The urodynamic parameters evaluated were the following:
      maximum cystometric capacity, urine loss due to cough, Valsalva leak point
      pressure, and detrusor overactivity (DO). The groups were homogeneous concerning
      age, parity, body mass index, and genital prolapse. Symptoms such as increase of
      urinary frequency (p=0.007) and urge urinary incontinence (p=0.004) were
      statistically more common in the FM group. DO was the statistically most common
      urodynamic observation in patients with FM (p=0.02). Regarding the questionnaires
      about quality of life, the patients with fibromyalgia and LUTS had the worst
      results in all fields. In conclusion, patients with FM and LUTS have detrusor
      overactivity more often as well as an increase of urinary frequency, contributing
      to the quality of life worsening.

PMID- 18317664
TI  - An anatomic study of the divisions of the lateral pterygoid muscle based on the
      findings of the origins and insertions.
AB  - The lateral pterygoid muscle has been generally described as a muscle composed of
      two separate heads, however, the border between these heads has not clearly
      identified. In the present study, we investigated the positional relationships
      between the muscle and the surrounding nerves, and examined the muscle bundle
      arrangements to determine the detailed information of the origins and insertions.
      We used 94 specimens of 52 Japanese cadavers (29 males and 25 females) for the
      investigations of the nerve courses, and randomly chose and used 10 specimens of
      5 (2 males and 3 females) cadavers from above-mentioned 52 cadavers for the
      detailed examinations of the muscle fiber constructions. In some specimens, the
      buccal nerve passed through the gap in the muscle, however, in many cases the
      nerve pierced the muscle. The muscle inserted into the medial half of the
      anterior surface and the medial surface of the condylar process. Only a thin
      superficial layer of the muscle fibers was attached to the inferior surface of
      the articular disc. According to the positions of the origins and insertions of
      the muscle and the positional relationships to the nerves, the muscle was not
      clearly divided into heads. The detailed findings of the origins and insertions
      of the present study suggest that the muscle is a single muscle with no clear
      border, containing fibers of various directions. A two-head muscle pattern would
      be indicated by the differences of the convergences of the muscle fibers.

PMID- 18317665
TI  - Review on balloon aortic valvuloplasty: a surgeon's perspective in 2008.
AB  - The article by Sack and co-workers published in this issue presents the results
      of a retrospective study on the treatment of severe calcified aortic stenosis
      (AS) by means of balloon aortic valvuloplasty (BAV) in the elderly patient. While
      arguing that BAV should be used in patients unfit for surgical aortic valve
      replacement (AVR) due to relative contraindications their results reveal widely
      unfavourable outcomes particularly with regard to survival and mortality rates.
      In contrast, surgical AVR yields excellent results in the mid- and long-term
      follow-up even in a high-risk patient population. In the rare case of real
      contraindications to surgical AVR transcatheter valve implantation techniques
      seem to be the more adequate alternative today.

PMID- 18317666
TI  - Therapy effects of green tea in a patient with systemic light-chain amyloidosis.

PMID- 18317667
TI  - Effects of cardiac rehabilitation program on exercise capacity and chronotropic
      variables in patients with orthotopic heart transplant.
AB  - AIM: To evaluate the effects of home- and hospital-exercise programs on exercise
      capacity and chronotropic variables in patients with heart transplantation.
      METHODS: Forty patients were randomized into two groups either hospital- or home
      based exercise program. The patients were compared, before and after the
      rehabilitation program, with respect to maximal oxygen uptake (pVO(2)),
      chronotropic variables [heart rate reserve (HRR(e)), heart rate recovery
      (HRR(1)), and chronotropic response index (CRI)] and Duke Treadmill Score (DTS).
      RESULTS: Hospital-based exercise group has shown a significant recovery in post
      exercise pVO(2) (pre-exercise 16.73 +/- 3.9 ml/kg/min, post-exercise 19.53 +/-
      3.89 ml/kg/min, P = 0.002) and DTS (pre-exercise 4.74 +/- 1.17, post-exercise
      5.61 +/- 1.11, P = 0.002). A significant recovery in favor of the hospital-based
      exercise group was found in HRR(e) (pre-exercise 26.9 +/- 14.6, post-exercise
      34.6 +/- 14.6, P = 0.01). No significant change was observed in HRR(1) (pre
      exercise -1.38 +/- 1.04, post-exercise -1.21 +/- 1.89, P = 0.49) and CRI (pre
      exercise 0.44 +/- 0.23, post-exercise 0.48 +/- 0.20, P = 0.15) in hospital-based
      exercise group. No significant change was observed in any parameters of home
      based group (P > 0.05). CONCLUSION: A significant recovery was observed both in
      the functional capacity and the chronotropic response in hospital-based exercise
      program. Exercise programs that are planned to be performed under supervision in
      rehabilitation units are useful for the patients with heart transplant in terms
      of the exercise capacity and chronotropic variables.

PMID- 18317668
TI  - Risk predictors for adverse outcomes after percutaneous coronary interventions
      and their related costs.
AB  - OBJECTIVES: During recent years, numerous clinical and procedural risk factors
      for adverse outcomes after percutaneous coronary interventions (PCI) have been
      identified. Due to the high economic pressure in many national health care
      systems, it is of some interest whether these predictors of clinical risks
      represent also the main cost drivers. METHODS: Data of 770 patients undergoing
      PCI were retrospectively analyzed. Risk factors for PCI as well as angiographic
      classifications were adopted from the ACC/AHA Guidelines. In-hospital costs for
      each patient were obtained from thoroughly performed calculations for the
      national Diagnosis Related Groups database in Germany. RESULTS: Creatinine >2
      mg/dl (192% of average costs, P < 0.0001), EF <or= 35% (146%, P < 0.0001),
      presence of a thrombus (146%, P < 0.0001), PCI of a venous bypass (143%, P <
      0.0001), CCS class IV (123%, P < 0.0001), coronary three-vessel disease (119%, P
      < 0.0001) and age (112%, P = 0.014) were associated with both higher in-hospital
      mortality and costs. Furthermore, in patients with acute coronary syndromes the
      time delay from onset of symptoms until PCI had marked impact on costs.
      CONCLUSIONS: Most predictors for adverse outcome after PCI were also found to be
      major cost drivers. Moreover, time delay from onset of ACS to PCI had marked
      impact on costs and should be implemented in the reimbursement systems.

PMID- 18317670
TI  - Editorial.

PMID- 18317669
TI  - Treatment of in-stent restenosis with sirolimus-eluting-stents: results from the
      prospective German Cypher stent registry.
AB  - AIMS: Drug-eluting stents have been reported to effectively reduce in-stent
      restenosis (ISR). However, the effectiveness and safety have yet been
      investigated only in small trials or case series. The aim of this prospective
      large scale registry was to show that treatment of ISR with sirolimus eluting
      stents (SES) is safe, effective and feasible in daily routine. METHODS AND
      RESULTS: The German Cypher registry prospectively enrolled 6,555 patients
      undergoing implantation with SES for various indications, including 1,533
      patients treated for ISR. Follow-up data (median 6.6 months) of this cohort was
      available for 1,531 patients (99.8%). Of these patients 75.8% were male. Of these
      patients 36.5% (n = 552) presented with acute coronary syndromes. In total, 1,932
      SES were used with successful implantation in 98.9%. MI during hospitalization
      was observed in 0.7% (n = 11) while in-hospital mortality was only 0.1% (n = 2).
      MACE-rate at follow-up was 13.8% (n = 211) including a mortality of 1.3% (n = 20)
      and MI in 1.9% (n = 29). Total revascularization procedures including CABG (1.7%)
      were necessary in 12.3% (n = 186). Target vessel revascularization (TVR) rate was
      9.3% (n = 139) and thus similar to patients with de novo lesions (8.1%, P =
      0.69). Ten patients (0.65%) suffered from subacute stent thrombosis Vs. 0.24%
      observed in patients with de novo lesions (P = 0.03). CONCLUSION: This large
      registry confirms that treatment of ISR with sirolimus-eluting-stents is
      effective and save with good clinical results at index procedure and follow-up.
      TVR was not different from de novo lesions.

PMID- 18317671
TI  - A shift from adaptive to innate immunity: a potential mechanism of disease
      progression in multiple sclerosis.
AB  - Multiple sclerosis is postulated to be a T cell-mediated autoimmune disease
      characterised by a relapsing-remitting stage followed by a secondary progressive
      phase. The relapsing remitting phase may involve waves of proinflammatory Th1 and
      Th17 cells that infiltrate the nervous system, provoking a clinical attack. The
      activity of these cells is modulated by other populations of regulatory T cells
      and the balance between the pro-inflammatory and regulatory T cells is critical
      for determining disease activity. Promoting the activity of regulatory cells is a
      potentially beneficial therapeutic strategy, and probably contributes to the
      action of glatiramer acetate. The progressive phase of multiple sclerosis is
      believed to be secondary to neurodegenerative changes triggered by inflammation.
      The status of the innate immune system and its relationship to the stages of
      multiple sclerosis has been poorly defined until recently. However, recent data
      suggest that these results demonstrate abnormalities of dendritic cell activation
      or maturation may underlie the transition to the progressive phase of the
      disease. Preventing this transition, perhaps by acting at the level of the innate
      immune system, is an important treatment goal. The identification of biomarkers
      to predict disease course and treatment response is a major challenge in multiple
      sclerosis research. Studies using antigen arrays have identified antibody
      patterns related to CNS antigens and heat-shock proteins that are associated with
      different disease stages and with response to therapy. In the future, such
      antibody repertoires could be used as biomarkers for the diagnosis and evaluation
      of patients with multiple sclerosis, for matching treatments to individual
      patients and, potentially, to identify healthy individuals at risk for this
      autoimmune disease.

PMID- 18317672
TI  - Interplay between mechanisms of damage and repair in multiple sclerosis.
AB  - The neuropathology of multiple sclerosis is characterised by focal damage to
      white matter. However, tissue damage is also present in the cortical grey matter,
      with a particularly high prevalence of cortical demyelination being observed in
      secondary progressive and primary progressive forms of the disease. The presence
      of meningeal B-cell follicle-like structures, which frequently appear during the
      secondary progressive phase of disease, may be involved in the formation of these
      subpial cortical lesions. Diffuse white matter inflammation accompanied by axonal
      damage can also be observed in normal appearing white matter and, again, this is
      more prominent in chronic progressive forms of multiple sclerosis than in acute
      stages of disease. Axonal damage is a particularly important component of the
      pathology of multiple sclerosis and appears to be a critical determinant of
      clinical outcome. Axons appear to become vulnerable to injury as a result of loss
      of their myelin sheaths. Remyelination represents an important mechanism of
      tissue repair in multiple sclerosis and already occurs at an early stage of
      lesion development and in both white and grey matter lesions. The extent of
      remyelination appears to be greater in cortical lesions and in lesions further
      from the ventricles. There is important heterogeneity between patients in terms
      of the extent of remyelination, which may reflect underlying differences in
      pathogenetic mechanisms between patients.

PMID- 18317673
TI  - The biology of CNS remyelination: the key to therapeutic advances.
AB  - Remyelination, the process by which new myelin sheaths are restored to
      demyelinated axons, represents one of the most compelling examples of adult
      multipotent progenitor cells contributing to regeneration of the injured CNS.
      This process can occur with remarkable efficiency in both clinical disease, such
      as multiple sclerosis, and in experimental models, revealing an impressive
      ability of the adult CNS to repair itself. However, the inconsistency of
      remyelination in multiple sclerosis, and the loss of axonal integrity that
      results from its failure, makes enhancement of remyelination an important
      therapeutic objective. Identifying potential targets requires a detailed
      understanding of the cellular and molecular mechanisms of remyelination. A
      critical step in achieving effective remyelination is the differentiation of
      precursor cells into mature oligodendrocytes. In experimental models of
      demyelinating disease in aged animals, as well as in multiple sclerosis, such
      differentiation appears to be impaired. This is due, at least in part, to changes
      in environmental signals governing remyelination. In particular, myelin debris
      within lesions appears to contain powerful inhibitors of precursor cell
      differentiation. Efficient removal of myelin debris by macrophages may thus
      facilitate differentiation and permit successful remyelination of damaged axons.
      This may represent a promising therapeutic target for promoting remyelination in
      multiple sclerosis and thus limiting the accumulation of irreversible
      neurological disability.

PMID- 18317674
TI  - Glatiramer acetate: evidence for a dual mechanism of action.
AB  - Glatiramer acetate is a disease-modifying drug approved for the treatment of
      relapsing-remitting multiple sclerosis. Since its discovery almost four decades
      ago, and in particular since the observation of its beneficial clinical effects
      in the late 1980s and early 1990s, numerous data have been generated and
      contribute pieces of a puzzle to help explain the mechanism of action of
      glatiramer acetate. Two major themes have emerged, namely (i) the induction of
      glatiramer acetate-reactive TH2 immunoregulatory cells, and (ii) the stimulation
      of neurotrophin secretion in the central nervous system that may promote neuronal
      repair.

PMID- 18317675
TI  - Rationale for early intervention with immunomodulatory treatments.
AB  - The McDonald diagnostic criteria have allowed the formal diagnosis of multiple
      sclerosis in patients presenting with clinically isolated syndromes to be brought
      forward. Evidence from research suggests that many patients with clinically
      isolated syndromes or early multiple sclerosis should be treated with disease
      modifying drugs at an early stage, since disease experience during the first few
      years are likely to have significant impact on the long-term evolution of the
      disease. Histopathological studies have demonstrated the presence of axonal
      transection in patients with less than five years of disease duration, and
      especially during the first twelve months. Natural history studies have shown
      that the number of relapses occurring during the first few years of the disease
      is related to the time to accrued disability. Moreover, longitudinal studies on
      patients with clinically isolated syndromes have shown that the presence of even
      a very small number of baseline MRI lesions is associated with an increased risk
      of developing clinically definite multiple sclerosis and, more importantly, that
      the increase in volume of the lesions seen in the first five years correlates
      with the degree of disability in the longer term. For example, long-term follow
      up of a large cohort of patients presenting with a clinically isolated syndrome
      in Barcelona has shown that the number of Barkhof criteria fulfilled at baseline
      was correlated with the risk of relapse, EDSS disability scores at five years and
      the risk of reaching given EDSS disability thresholds. Three randomised clinical
      trials in patients with a clinically isolated syndrome and abnormal brain MRI
      have shown significant benefit of initiating early therapy with beta-interferons,
      and a similar study is underway with glatiramer acetate. It is concluded that
      choosing the right time to introduce treatment is critically important for
      outcome and the earlier treatment is initiated, the better the outcome.

PMID- 18317676
TI  - Switching algorithms: from one immunomodulatory agent to another.
AB  - In spite of the availability of six disease-modifying treatments for multiple
      sclerosis, a significant minority of patients fail to respond adequately to
      treatment. Switching immunomodulatory therapy is a potentially useful treatment
      strategy in such patients. Several factors contribute to the need to switch
      between immunomodulatory treatments, including the variable response to drug
      treatment, the timing and choice of therapy, disease severity, and the occurrence
      of neutralising antibodies. Guidelines have been proposed to define treatment
      response, integrating both clinical and imaging criteria. Several observational
      studies, principally evaluating a switch from beta-interferons to glatiramer
      acetate, have demonstrated that switching treatments is both safe and effective
      in patients with inadequate control of disease activity or who are experiencing
      unacceptable side effects with their original treatment. A treatment algorithm is
      proposed for decision-making when switching therapies appears warranted.

PMID- 18317677
TI  - Combination therapies in multiple sclerosis.
AB  - The last years have seen enormous progress in our understanding of
      pathophysiology of multiple sclerosis. In addition, the armamentarium of
      available immunomodulatory or immunosuppressive therapies has greatly increased,
      especially for the relapsing remitting form of the disease. Since their
      therapeutic efficacy is often limited in individual patients, it is conceivable
      that combination therapies may bring improved clinical efficacy while managing
      increasing side effects and toxicity. The combination of agents with additive or
      synergistic modes of action is of particular interest. Combination of the two
      classes of recognised firstline treatment, a beta-interferon and glatiramer
      acetate is currently under evaluation in a large Phase III trial. However, there
      are theoretical reasons for thinking that such a combination may not be
      particularly beneficial. None of the combination studies performed with beta
      interferons to date have shown unequivocal evidence of benefit, including
      combinations with statins, natalizumab and azathioprine. On the other hand, for
      glatiramer acetate, the combination with mitoxantrone used as induction therapy
      may be of interest and preliminary data on combination with minocycline are also
      promising.

PMID- 18317678
TI  - The place of conventional MRI and newly emerging MRI techniques in monitoring
      different aspects of treatment outcome.
AB  - Magnetic resonance imaging (MRI) is the most important paraclinical measure for
      assessing and monitoring the pathologic changes implicated in the onset and
      progression of multiple sclerosis (MS). Conventional MRI sequences, such as T1
      weighted gadolinium (Gd) enhanced and spin-echo T2-weighted imaging, only provide
      an incomplete picture of the degree of inflammation and underlying
      neurodegenerative changes in this disease. Two- and three-dimensional fluid
      attenuated inversion recovery and double inversion recovery sequences allow
      better identification of cortical, periventricular and infratentorial lesions.
      Ultra-high field strength MRI has the potential to detect subpial cortical and
      deep gray matter lesions. Unenhanced T1-weighted imaging can reveal hypointense
      black holes, a measure of chronic neurodegeneration. Magnetization transfer
      imaging (MTI) is increasingly used to characterize the evolution of MS lesions
      and normal-appearing brain tissue. Evidence suggests that the dynamics of
      magnetization transfer changes correlate with the extent of demyelination and
      remyelination. Magnetic resonance spectroscopy, which provides details on tissue
      biochemistry, metabolism, and function, also has the capacity to reveal
      neuroprotective mechanisms. By measuring the motion of water, diffusion imaging
      can provide information about the orientation, size, and geometry of tissue
      damage in white and gray matter. These advanced non-conventional MRI techniques
      relate better to clinical impairment, disease progression, accumulation of
      disability, and have the potential to detect neuroprotective effects of
      treatment. Although detecting the status of neuronal integrity using MRI
      techniques continues to improve, a "gold standard" model remains to be
      established.

PMID- 18317679
TI  - The search for a balance between short and long-term treatment outcomes in
      multiple sclerosis.
AB  - Multiple sclerosis is a lifelong, immune-mediated progressive disorder. The early
      age of onset and the chronic nature of the disease with accumulation of physical
      disability, demand a long-term ("lifelong") management, including disease
      modifying immunomodulatory therapies and symptomatic treatments. The ultimate
      goal in the long-term management of multiple sclerosis is to prevent or delay the
      appearance of permanent neurological disability. Due to improvements in the
      diagnosis of multiple sclerosis, it is now possible to initiate treatment early
      in the disease process. To this end, first-line immunomodulatory treatments such
      as glatiramer acetate and beta-interferons are available that reduce the rate of
      relapses and disease activity as measured with magnetic resonance imaging.
      However, the short duration of clinical trials provides little information about
      long-term changes in disability over time. In the case of glatiramer acetate, a
      long-term, openlabel extension of the pivotal trial has provided prospective data
      on systematic regular follow-up of all patients who had ever received the drug
      during the original trial or its extension. Of 232 patients analysed, 108 were
      still participating in the study an average of ten years after treatment was
      initiated. Despite the limitations of open-label trials, this study has provided
      some evidence for a sustained reduction in frequency and severity of relapses and
      in the rate of accrual of disability. Such long-term data, which demonstrate
      safety, tolerability and sustained clinical benefit, help improve patient care
      and may contribute to patients taking a more positive view of treatment.
      Effective immunomodulatory treatment needs comprehensive information and
      education of the patient to establish long-term adherence, a critical determinant
      of long-term outcome. A multidisciplinary approach through a health care team is
      the optimal strategy, with encouragement to continue the therapy.

PMID- 18317680
TI  - Sourdough-leavened bread improves postprandial glucose and insulin plasma levels
      in subjects with impaired glucose tolerance.
AB  - Sourdough bread has been reported to improve glucose metabolism in healthy
      subjects. In this study postprandial glycaemic and insulinaemic responses were
      evaluated in subjects with impaired glucose tolerance (IGT) who had a meal
      containing sourdough bread leavened with lactobacilli, in comparison to a
      reference meal containing bread leavened with baker yeast. Sixteen IGT subjects
      (age range 52-75, average BMI 29.9 +/- 4.2 kg/ m2) were randomly given a meal
      containing sourdough bread (A) and a meal containing the reference bread (B) in
      two separate occasions at the beginning of the study and after 7 days. Sourdough
      bread was leavened for 8 h using a starter containing autochthonous Saccharomyces
      cerevisiae and several bacilli able to produce a significant amount of D-and L
      lactic acid, whereas the reference bread was leavened for 2 h with commercial
      baker yeast containing Saccharomyces cerevisiae. Plasma glucose and insulin
      levels were measured at time 0, 30, 60, 120, and 180 min. In IGT subjects
      sourdough bread induced a significantly lower plasma glucose response at 30
      minutes (p = 0.048) and a smaller incremental area under curve (AUC) delta 0-30
      and delta 0-60 min (p = 0.020 and 0.018 respectively) in comparison to the bread
      leavened with baker yeast. Plasma insulin response to this type of bread showed
      lower values at 30 min (p = 0.045) and a smaller AUC delta 0-30 min (p = 0.018).
      This study shows that in subjects with IGT glycaemic and insulinaemic responses
      after the consumption of sourdough bread are lower than after the bread leavened
      with baker yeast. This effect is likely due to the lactic acid produced during
      dough leavening as well as the reduced availability of simple carbohydrates.
      Thus, sour-dough bread may potentially be of benefit in subjects with impaired
      glucose metabolism.

PMID- 18317681
TI  - Auditory processing of sine tones before, during and after ECT in depressed
      patients by fMRI.
AB  - Our goal was to assess treatment effects of electroconvulsive therapy (ECT) on
      acoustic processing in major depression. We hypothesized that (1) depression is
      related to functional alterations in auditory networks, and that (2) pre
      treatment alterations in auditory networks are reversible through treatment with
      ECT. Acoustic perception of 20 severely depressed and 20 age and gender matched
      healthy controls was investigated by 3 T functional magnetic resonance imaging
      employing repeated stimulation by sine tones. Prior to ECT, depressed patients
      presented a multimodal recruitment of additional brain areas including regions of
      the secondary visual system (cuneus, lingualis) and the medial frontal cortex.
      During ECT, signal intensities were reduced compared to pre-ECT values and
      controls. Activation of several regions increased after ECT. Our data suggest
      that depression is accompanied by cortical dysfunction including impaired
      auditory processing of non-speech stimuli. This might be based on overall
      alterations of brain metabolism indicating functional impairment.

PMID- 18317682
TI  - Multiple aspects related to self-awareness and the awareness of others: an
      electroencephalography study.
AB  - The effect of possessive pronouns on the encoding of pronoun-noun associations
      (e.g., my garden) was investigated using the electroencephalography (EEG).
      Following an alphabetical, semantic and a contextual encoding instruction depth
      of noun processing was varied within three separate experiments in order to
      manipulate the grade of awareness related to verbal information processing. Only
      for the semantic encoding task (lexical decision) response time was significantly
      longer for nouns associated with the pronoun "mein" (German for "my") than for
      nouns associated with the pronoun "ein" (German for "a") although pronouns were
      not to be consciously processed at all. Following recognition tests related to
      nouns (without their previously associated pronouns) revealed no significant
      differences related to the number of correctly identified repeated nouns (hits)
      depending on the kind of previously associated pronoun. The analysis of
      neurophysiological data revealed a time range between about 250 ms and 400 ms
      after stimulus onset within which significant pronoun x electrode interactions
      occurred. No interaction with depth of word processing was found. Overlaid EEG
      curves, t maps and low resolution brain electromagnetic tomography (LORETA)
      demonstrate that in this time range "mein" and "sein" associated conditions
      elicit similar brain activity, both more negative, compared to the "ein"
      associated condition over occipital electrodes. On the other hand, at left
      temporal sites the "mein" condition elicited more negative potentials than both
      other conditions. It is interpreted that EEG recordings reveal two relevant
      areas, which are sensitive to the concept of a person (as represented by a
      personal pronoun) between about 250 ms and 400 ms after stimulus onset. One area
      is located in the occipital region and can distinguish between personal
      engagement and a neutral condition and the other area is located in the temporal
      region and is able to distinguish between oneself and somebody else. Together
      with our previous MEG results (Walla et al. in Neuropsychologia 45:796-809, 2007)
      we want to combine the inferences in the frame of the "multiple aspects"
      hypothesis related to research on self-awareness and the awareness of others.

PMID- 18317683
TI  - Glial and neuronal damage markers in patients with anorexia nervosa.
AB  - Anorexia nervosa (AN) commonly arises during adolescence leading to interruptions
      of somatic and psychological development as well as to atrophic brain changes. It
      remains unclear whether these brain changes are related to the loss of neurons,
      glia, neuropil or merely due to fluid shifts. We determined leptin levels and two
      brain-derived damage markers: glial fibrillary acidic protein (GFAP) and neuron
      specific enolase (NSE) of 43 acute AN patients and 50 healthy control woman
      (HCW). Peripheral GFAP and NSE concentrations of AN patients were not elevated
      and not different from HCW. Subjects with particularly low leptin concentration,
      indicating severe malnutrition, did not show abnormal values either. During
      weight recovery the marker proteins remained unchanged. Our preliminary results
      are in line with neuroimaging studies supporting the reversibility of brain
      changes in AN and do not substantiate hypotheses relying on the extensive damage
      of brain cells as an explanation for cerebral atrophy in AN.

PMID- 18317684
TI  - Dethiobacter alkaliphilus gen. nov. sp. nov., and Desulfurivibrio alkaliphilus
      gen. nov. sp. nov.: two novel representatives of reductive sulfur cycle from soda
      lakes.
AB  - Anaerobic enrichments with H2 as electron donor and thiosulfate/polysulfide as
      electron acceptor at pH 10 and 0.6 M total Na+ yielded two non sulfate-reducing
      representatives of reductive sulfur cycle from soda lake sediments. Strain AHT 1
      was isolated with thiosulfate as the electron acceptor from north-eastern
      Mongolian soda lakes and strain AHT 2-with polysulfide as the electron acceptor
      from Wadi al Natrun lakes in Egypt. Both isolates represented new phylogenetic
      lineages: AHT 1-within Clostridiales and AHT 2-within the Deltaproteobacteria.
      Both bacteria are obligate anaerobes with respiratory metabolism. Both grew
      chemolithoautotrophically with H2 as the electron donor and can use thiosulfate,
      elemental sulfur and polysulfide as the electron acceptors. AHT 2 also used
      nitrate as acceptor, reducing it to ammonia. During thiosulfate reduction, AHT 1
      excreted sulfite. dsrAB gene was not found in either strain. Both strains were
      moderate salt-tolerant (grow up to 2 M total Na+) true alkaliphiles (grow between
      pH 8.5 and 10.3). On the basis of the phenotypic and phylogenetic data, strains
      AHT 1 and AHT 2 are proposed as new genera and species Dethiobacter alkaliphilus
      and Desulfurivibrio alkaliphilus, respectively.

PMID- 18317685
TI  - Pituitary gland involvement by a gamma delta hepatosplenic lymphoma, a mimicker
      of pituitary adenoma: report of a rare case.
AB  - The authors report an unusual case of hepatosplenic T-cell lymphoma in a 41-year
      old male patient. He presented initially with low grade fever, hepatosplenomegaly
      and pancytopenia. Splenectomy was done which showed infiltration of red pulp by
      monomorphic lymphocytes. Liver was also infiltrated with similar cells. A
      provisional diagnosis of hairy cell leukemia was made. Subsequently, after 6
      months he was found to have a sellar mass, which on microscopy revealed lymphoma
      cells. These cells were positive for leukocyte common antigen and T-cell markers.
      Finally, based on overall clinical, histomorphological and immunophenotypic
      features, a diagnosis of hepatosplenic T-cell lymphoma, possibly gamma delta
      type, involving pituitary gland was established. On follow up, this patient
      showed evidence of bone marrow involvement and died after 1.5-year of diagnosis.
      This case highlights the involvement of rare site by a rare lymphoma and should
      be kept in mind in the differential diagnoses of pituitary tumors.

PMID- 18317686
TI  - Expression of vascular endothelial growth factor-A and mRNA stability factor HuR
      in human meningiomas.
AB  - We studied the expression of vascular endothelial growth factor-A (VEGF-A) and
      mRNA stability factor HuR in 40 supratentorial meningiomas using RT-PCR, ELISA
      and immunohistochemistry, and analyzed their associations with the
      clinicopathological characteristics, including microvascular density (MVD),
      peritumoral brain edema (PTBE), histological subtypes and grades, and the
      performance of preoperative arterial embolization. Furthermore, we investigated
      the involvement of HuR in the upregulation of VEGF-A expression using primary
      meningioma cell cultures. The level of VEGF-A is elevated in meningiomas with
      PTBE and in higher grade meningiomas. Preoperative arterial embolization did not
      significantly increase the level of VEGF-A, but it did increase the expression of
      HuR in tumor tissues. HuR expression was correlated positively with VEGF-A
      expression in meningioma tissues. In in vitro experiments, hypoxia induced the
      upregulation of VEGF-A expression and the cytoplasmic translocation of HuR
      protein in meningioma cells, and inhibition of the cytoplasmic translocation of
      HuR reduced the upregulation of VEGF-A expression in meningioma cells. These
      findings suggest that the expression of VEGF-A relates to the development of PTBE
      with meningiomas and the histological grade, and that HuR is involved in the
      upregulation of VEGF-A expression in human meningiomas.

PMID- 18317687
TI  - Extramedullary plasmacytoma presented as a non-functional invasive pituitary
      macro-adenoma.
AB  - Pituitary adenomas are the most common etiology of sellar masses. Intra-sellar
      plasmacytomas are rare causes of sellar tumors of non-pituitary origin and may
      mimic nonfunctional pituitary adenomas clinically and radiologically. We report
      an uncommon case of an intrasellar plasmacytoma presenting as the only
      manifestation of multiple myeloma.

PMID- 18317688
TI  - Glioblastoma multiforme with an abscess: case report and literature review.
AB  - An intratumoral or peritumoral microbial intracranial abscess is an infrequent
      diagnosis. The development of this complication may not be preceded by apparent
      local or general infection in all cases. To identify this diagnosis by
      radiological (MRI) or laboratory investigations is very intricate. Nevertheless,
      the recommended life-saving strategy is early surgery with resolution of both the
      tumor and infection. If subsequent oncological treatment is required, it has to
      be adjusted for prevention of re-inflammation. The described patient suffered
      from an intracranial abscess superimposed on a Glioblastoma Multiforme. The
      confirmed etiological agent was Staphylococcus aureus. The suspected route of
      microbial migration and colonization in this tumor was bacteremia via agents from
      thrombophlebitis. The patient is in a good condition following surgery,
      antimicrobial treatment, and radiotherapy.

PMID- 18317689
TI  - Successful outcome with tandem myeloablative chemotherapy and autologous
      peripheral blood stem cell transplants in a patient with atypical
      teratoid/rhabdoid tumor of the central nervous system.
AB  - Atypical teratoid rhabdoid tumors (ATRT) are highly malignant tumors of the
      central nervous system with a peak incidence in children less than 3 years of
      age. Despite multimodal therapy including surgery, radiation and chemotherapy,
      the prognosis remains dismal. No specific treatment guidelines are defined for
      ATRTs but a gross total resection and radiation therapy (RT) appear to improve
      overall outcome. In children less than 3 years of age, the prognosis is dismal
      due in part to the reluctance to utilize RT given its severe neurological
      sequelae. To avoid RT in this age group, intensification of chemotherapy has been
      tried and has shown to improve outcome. Myeloablative chemotherapy followed by
      autologous stem cell re-infusion has been used as a modality to intensify therapy
      but there are no reports of use of tandem myeloablative regimens and autologous
      stem cell re-infusions for treatment of ATRT. We herein report the case of a 4
      month-old boy with ATRT with partial resection of his tumor who achieved complete
      remission using tandem high-dose therapy followed by autologous peripheral blood
      stem cell re-infusions despite having biopsy proven disease at the time of
      starting the tandem regimens. This was achieved without the use of RT as a
      treatment modality.

PMID- 18317690
TI  - Knockdown of GluR1 expression by RNA interference inhibits glioma proliferation.
AB  - High-grade gliomas release excitotoxic concentrations of glutamate which
      contributes to their malignant phenotype. To improve our understanding of the
      mechanisms by which glutamate enhances tumor growth and invasion, we examined
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-mediated
      signaling in glioma cell lines. shRNA was used to stably knockdown GluR1, the
      most abundant AMPA receptor subunit in glioma, to evaluate its role in tumor
      signaling, proliferation and tumorigenicity. In a tissue array, there was a
      statistically significant increase in GluR1 expression in glioblastoma samples
      compared to anaplastic astrocytoma and low-grade tumors. In vitro, we observed a
      time and dose-dependent increase in MAPK phosphorylation following exposure to
      AMPA, which was blocked with AMPA receptor antagonists and the MEK1 inhibitor
      PD98059. Retroviral delivery of GluR1 shRNA in U251 and U87 glioma cells reduced
      GluR1 protein expression, inhibited AMPA-mediated increases in MAPK
      phosphorylation, and decreased glioma proliferation in vitro. U251 and U87
      shGluR1 cells implanted into the flanks of nude mice grew slower than controls,
      which correlated with a decrease in proliferation measured by Ki-67 staining and
      an increase in apoptosis. These results suggest that AMPA receptors are
      abundantly expressed in high-grade gliomas and gene silencing of the GluR1 AMPA
      receptor subunit results in abrogation of AMPA-mediated signaling and tumor
      growth.

PMID- 18317691
TI  - Correlation of F-18-fluoro-ethyl-tyrosin uptake with vascular and cell density in
      non-contrast-enhancing gliomas.
AB  - OBJECTIVE: Even without contrast enhancement on MRI scans gliomas can show
      histological features of anaplasia. These tumors are heterogeneous regarding
      anaplastic and non-anaplastic areas. Increased amino acid uptake was shown to be
      associated with dismal prognosis in gliomas. We investigated histological
      correlates of tumor grading in biopsies obtained from regions with maximum amino
      acid uptake revealed by F-18-fluoro-ethyl-tyrosin positron emission tomography
      (FET-PET). METHODS: We included 22 patients with non-contrast enhancing lesions
      on MRI scans. PET was performed 10 min after FET injection, and the area of
      maximum FET uptake was chosen as the biopsy target. In 13 patients neuronavigated
      biopsies were obtained during tumor resection. Nine patients had a stereotactic
      biopsy. The ratio of maximum standardized uptake value (SUV) to background was
      calculated. Histological specimens were classified and graded according to world
      health organization (WHO) criteria. We investigated cell and vascular density,
      mitotic activity, proliferation index, microvascular proliferation, nuclear
      pleomorphism, necrosis and immunoreactivity of LAT1 (SLC7A5), an amino acid
      transporter with prognostic impact in gliomas. RESULTS: 12 of the 22 non-contrast
      enhancing gliomas corresponded to anaplastic astrocytomas WHO grade III. Vascular
      and cellular density was correlated highly to the SUV ratio (P = 0.0015 and P =
      0.0021, respectively), but with no nuclear pleomorphism, mitotic activity, Mib-1
      immunoreactivity, or microvascular proliferation. Thus, no correlation was found
      between FET uptake and tumor grade. CONCLUSION: FET-PET correlates with vascular
      and cell density in non-contrast enhancing gliomas. Although tumor grade cannot
      be predicted, clinical use of FET PET as an indicator for neovascularization
      should be addressed in future studies.

PMID- 18317692
TI  - Multiple spinal metastases of cranial gliosarcoma: a case report and review of
      the literature.
AB  - Gliosarcoma is a rare brain tumor that consists of both glial and mesenchymal
      components. We report the case of a 68-year-old female with cranial gliosarcoma
      metastatic to the spinal cord. Initially, the patient was diagnosed with cranial
      gliosarcoma and treated with surgical resection followed by radiotherapy. Four
      months after she completed treatment, she presented with a sudden onset of
      hemiplegia. MRI (Magnetic Resonance Imaging) scan demonstrated two masses at the
      thoracic spinal cord. Immediate surgery was performed and the lesions were
      resected. No further therapy was recommended due to the poor condition of the
      patient. The patient subsequently died 3 months after diagnosis of the spinal
      cord metastases. There are about 20 reported cases of metastatic gliosarcoma and
      most focus on systemic metastases of gliosarcoma. Spinal cord metastases are,
      however, very rare and here we report such a case. Available literature on
      metastatic gliosarcoma was also reviewed.

PMID- 18317693
TI  - Large cell medulloblastoma with myogenic and melanotic differentiation: a case
      report with molecular analysis.
AB  - We present a case of large cell medulloblastoma with myogenic and melanotic
      differentiation arising in the cerebellar vermis of a 2-year-old boy and
      following an aggressive clinical course. Histologic and immunohistochemical
      features of this tumor include primitive neuronal, rhabdomyoblastic, and
      pigmented epithelial elements, along with large cell features.
      Immunohistochemical and molecular data (c-myc gene amplification and the presence
      of isochromosome 17q) support the contention that this histologically diverse
      tumor represents a pattern of medulloblastoma with striated muscle and pigmented
      epithelial differentiation, rather than a teratoma or a cerebellar variant of
      melanotic neuroectodermal tumor of infancy ('progonoma').

PMID- 18317694
TI  - Complete response after one cycle of temozolomide in an elderly patient with
      glioblastoma and poor performance status.
AB  - There is no standard of care for elderly patients with glioblastoma (GBM) and
      poor performance status. A 79-year-old woman with GBM, aphasia, and hemiplegia
      achieved a complete response after only one cycle of temozolomide (TMZ)
      (150mg/m2/day over 5 days). Genomic profiling of the tumor demonstrated loss of
      chromosome 10 and MDM2 amplification, which are predictive of poor outcome. The
      MGMT promoter was methylated, and it is likely that this at least partially
      explains the exquisite chemosensitivity in our patient. This unusual case report
      suggests that TMZ warrants further investigation in elderly patients with poor
      performance status.

PMID- 18317695
TI  - Expression, purification and characterization of the sulfite reductase hemo
      subunit, SiR-HP, from Acidithiobacillus ferrooxidans.
AB  - Sulfite reductase (SiR) is a large and soluble enzyme which catalyzes the
      transfer of six electrons from NADPH to sulfite to produce sulfide. The sulfite
      reductase flavoprotein (SiR-FP) contains both FAD and FMN, and the sulfite
      reductase hemoprotein (SiR-HP) contains an iron-sulfur cluster coupled to a
      siroheme. The enzyme is arranged so that the redox cofactors in the FAD-FMN
      Fe(4)S(4)-Heme sequence make an electron pathway between NADPH and sulfite. Here
      we report the cloning, expression, and characterization of the SiR-HP of the
      sulfite reductase from Acidithiobacillus ferrooxidans. The purified SiR-HP
      contained a [Fe(4)S(4)] cluster. Site-directed mutagenesis results revealed that
      Cys427, Cys433, Cys472 and Cys476 were in ligating with the [Fe(4)S(4)] cluster
      of the protein.

PMID- 18317696
TI  - Ectopic expression of Expansin3 or Expansinbeta1 causes enhanced hormone and salt
      stress sensitivity in Arabidopsis.
AB  - Expansins are cell wall loosening proteins that appear to permit the microfibril
      matrix network to slide in growing plant cell walls, thereby enabling the wall to
      expand. To scrutinize possible impacts on plant growth and development when
      expansins are over-expressed, we characterized phenotypic alterations of the
      transgenic plants that constitutively expressed AtEXP3 or AtEXP-beta1 under
      control of 35S-CaMV promoter. Our results suggest that both AtEXP3-OX and
      AtXPbeta1-OX are very sensitive to salt stress. However, the mechanisms
      underlying their enhanced salt sensitivity appear to be different.

PMID- 18317697
TI  - P19 embryonal carcinoma cells: a new model for the study of endothelial cell
      differentiation.
AB  - P19 embryonal carcinoma cells were examined under different conditions of
      embryoid body (EB) formation to evaluate endothelial differentiation. A prominent
      capillary-like network including PECAM-1 positive cells and upregulated
      expression of endothelial markers Tie-1, Tie-2, Flk-1 and PECAM-1 were identified
      in the DMSO-treated group during EB formation as well as after VEGF treatment.
      About 4% of the P19 cells differentiated into PECAM-1 positive cells on day 14 of
      differentiation. These results suggest that the P19 cells have the potential for
      endothelial cell differentiation and provide a new model system for future
      research.

PMID- 18317698
TI  - Poly(lactic-co-glycolic acid) nanosphere as a vehicle for gene delivery to human
      cord blood-derived mesenchymal stem cells: comparison with polyethylenimine.
AB  - Polyethylenimine (PEI) is one of the most extensively studied non-viral vectors
      but its cytotoxicity limits its clinical value. PLGA nanospheres are
      biocompatible and can facilitate sustained release of plasmid DNA. This study
      compares the cytotoxicity and long-term transgene expression between PLGA
      nanosphere and PEI. PLGA nanospheres were significantly less cytotoxic than PEI
      at various concentrations. PLGA nanospheres induced significantly higher
      transgene expression in vitro for a longer duration (21 days) than PEI. We
      conclude that PLGA nanospheres have potential as gene delivery vehicles for use
      in gene therapy for diseases in which a long-term therapeutic gene expression
      regimen is necessary.

PMID- 18317699
TI  - Bone morphogenetic protein-2 enhances bone regeneration mediated by
      transplantation of osteogenically undifferentiated bone marrow-derived
      mesenchymal stem cells.
AB  - We have hypothesized that human bone marrow-derived mesenchymal stem cells
      (BMMSCs), that are not osteogenically differentiated prior to implantation, would
      regenerate bone extensively in vivo once exogenous bone morphogenetic protein-2
      (BMP-2) was delivered to the implantation site. BMP-2 released from heparin
      conjugated poly(lactic-co-glycolic acid) (HCPLGA) scaffolds stimulates osteogenic
      differentiation of cultured BMMSCs. Upon implantation, undifferentiated BMMSCs on
      BMP-2-loaded HCPLGA scaffolds induce far more extensive bone formation than
      either undifferentiated BMMSCs or osteogenically differentiated BMMSCs on HCPLGA
      scaffolds. These BMP-2-loaded HCPLGA scaffolds could prove invaluable for in vivo
      regeneration of bone from undifferentiated human BMMSCs.

PMID- 18317700
TI  - Random mutagenesis and recombination of sam1 gene by integrating error-prone PCR
      with staggered extension process.
AB  - An efficient method for creating a DNA library is presented in which gene
      mutagenesis and recombination can be introduced by integrating error-prone PCR
      with a staggered extension process in one test tube. In this process, less than
      15 cycles of error-prone PCR are used to introduce random mutations. After
      precipitated and washed with ethanol solution, the error-prone PCR product is
      directly used both as template and primers in the following staggered extension
      process to introduce DNA recombination. The method was validated by using
      adenosyl-methionine (AdoMet) synthetase gene, sam1, as a model. The full-length
      target DNA fragment was available after a single round. After being selected with
      a competitive inhibitor, ethionine, a mutated gene was obtained that increased
      AdoMet accumulation in vivo by 56%.

PMID- 18317701
TI  - A modified T-vector for simplified assembly of hairpin RNAi constructs.
AB  - We describe a modified T-vector, pGFPm-T, for direct cloning of RT-PCR products
      to generate bidirectional restriction fragments for assembly of hairpin
      containing RNAi vectors in the popular pFGC and pGSA binary vector backbone.
      Green fluorescence protein (GFP) is used as a visual reporter for direct
      selection of recombinants under UV illumination. The simplified cloning process
      enables a seamless workflow from candidate gene selection and RT-PCR verification
      to inverted repeat cloning, using a single pair of gene-specific primers.

PMID- 18317702
TI  - Enhanced tolerance to drought stress in transgenic tobacco plants overexpressing
      VTE1 for increased tocopherol production from Arabidopsis thaliana.
AB  - Tocopherol cyclase (VTE1, encoded by VTE1 gene) catalyzes the penultimate step of
      tocopherol synthesis. Transgenic tobacco plants overexpressing VTE1 from
      Arabidopsis were exposed to drought conditions during which transgenic lines had
      decreased lipid peroxidation, electrolyte leakage and H(2)O(2) content, but had
      increased chlorophyll compared with the wild type. Thus VTE1 can be used to
      increase vitamin E content of plants and also to enhance tolerance to
      environmental stresses.

PMID- 18317703
TI  - Application of conjugation using phiC31 att/int system for Actinoplanes
      teichomyceticus, a producer of teicoplanin.
AB  - Actinoplanes teichomyceticus produces teicoplanin, which is a glycopeptide
      antibiotic for Gram-positive pathogenic bacteria and methicillin-resistant
      Staphylococcus aureus (MRSA). For a molecular genetic study of A.
      teichomyceticus, an effective transformation method using the conjugal transfer
      of DNA from E. coli to spores of A. teichomyceticus was established for the first
      time, based on the bacteriophage varphiC31 att/int system, in the genus of
      Actinoplanes. The high frequency of transconjugation was obtained on MS medium
      containing 40 mM MgCl(2), using 1.25 x 10(8) E. coli donor cells and 10(5) spores
      without a heat treatment. In addition, by cloning and sequencing the attB site A.
      teichomyceticus was shown to contain a single attB site within an ORF coding for
      a pirin homolog. Also, its attB site sequence showed high homology to that of
      Streptomyces lividans, unlike the case of Kitasatospora setae despite being a non
      Streptomyces actinomycete, which seems to be closely related to the high
      transconjugation frequency of A. teichomyceticus.

PMID- 18317704
TI  - Biodegradation of gaseous styrene by Brevibacillus sp. using a novel agitating
      biotrickling filter.
AB  - A novel biofilter with an agitator to control excessive biomass accumulation, the
      agitating biotrickling filter (ABTF) system, was developed for treatment of
      gaseous styrene using Brevibacillus sp. as the sole microorganism the ABTF
      exhibited an elimination capacity of 3 kg styrene m(-3) day(-1). After 110 days,
      the biodegradation efficiency decreased because of the clogging. The excess
      biomass was effectively removed by agitation. After the first agitation step,
      42.4 g biomass was eliminated, and the removal efficiency increased from 60% to
      95%. Stable operation of the ABTF was achieved by controlling the biomass
      accumulation via the agitation of the filter bed.

PMID- 18317705
TI  - Effects of short-term supplementation of clinoptilolite in colostrum and milk on
      the concentration of some serum minerals in neonatal dairy calves.
AB  - In recent years, the use of both natural and synthetic zeolites in animal
      nutrition has increased mainly to improve their performance, health, and to
      protect against mycotoxin intoxication. Thirty calves were used in the present
      study for the determination of some physiologic effects of clinoptilolite
      supplementation. The animals were divided equally into three groups (control,
      test 1, and test 2). The three groups of calves were homogeneous for parity of
      dams, sex, and month of birth. For group test 1, clinoptilolite in the
      concentration of 2% of each colostrum meal was added for 48 h, and for group test
      2, clinoptilolite in the concentration of 2% was added to each colostrum and milk
      meal for 14 days. Blood samples were taken from all calves 12 h after birth and
      at the end of the first, second, third, forth, fifth, and sixth weeks of life.
      Calcium (Ca), phosphorus (P), magnesium (Mg), iron (Fe), sodium (Na), and
      potassium (K) were determined in the serum. For statistical analysis of data, a
      repeated measures approach using analysis of variance (ANOVA) with mixed linear
      models was used. Clinoptilolite supplementation had significant effect on the
      concentrations of calcium, phosphorus, sodium, and iron. The concentrations of Fe
      significantly higher in test group 2 than other trial groups (p < 0.05). Calcium
      concentrations were significantly higher in serum of clinoptilolite-treated than
      control calves (p < 0.05). The concentrations of phosphorus were significantly
      lower in test groups than control group (p < 0.05). Sodium concentrations were
      significantly higher in clinoptilolite-supplemented groups than control calves (p
      < 0.05). Potassium and magnesium concentrations were not affected by
      clinoptilolite supplementation. Clinoptilolite supplementation could promote iron
      levels in serum and better hemopoiesis and prevent pathologic or physiologic drop
      of red blood cell (RBC) parameters in supplemented calves during a first few
      weeks of life. According to higher need and utilization of Ca in growing animals,
      clinoptilolite supplementation could increase available Ca. Based on the results
      of the present study and the importance of dietary phosphorus in many physiologic
      processes, the level of phosphorus in diet of neonatal dairy calves must be
      considered and adapted when clinoptilolite was supplemented. With an adequate
      supply of good quality drinking water, cattle can tolerate large quantities of
      dietary sodium chloride. Thus, it seems that significant increase in serum Na
      concentration during short-term supplementation of clinoptilolite in neonatal
      calves could be well tolerated without any adverse effects.

PMID- 18317706
TI  - Environmental and kinetic parameters for Cr(VI) bioreduction by a bacterial
      monoculture purified from Cr(VI)-resistant consortium.
AB  - Hexavalent chromium, Cr(VI), is toxic to living systems. Widespread contamination
      of water and soil by Cr(VI) present a serious public health problem. Chromium
      resistant bacteria can reduce and detoxify Cr(VI). Twelve bacteria resistant to
      high concentrations of Cr(VI) were isolated from soil enrichment cultures.
      Environmental parameters and kinetic parameters of Cr(VI) bioreduction by one
      monoculture isolate, identified by 16S rRNA gene sequence as Bacillus sp. PB2,
      were studied. The optimal temperature for growth and Cr(VI) reduction was 35
      degrees C. The isolate grew luxuriantly and substantially reduced Cr(VI) at
      initial pH 7.5 to 9. Maximal Cr(VI) bioreduction occurred at initial pH 8.0.
      Substantial Cr(VI) bioreduction was observed in salt media, but removal
      efficiency was inversely related to salt concentration (1-9%). Michaelis-Menten
      hyperbolic equation and the Lineweaver-Burk double reciprocal plot were
      comparatively employed to determine the k (m) and V (max) of Cr(VI) bioreduction.
      A k (m) of 82.5 microg mL(-1) and V (max) of 7.78 microg mL(-1) h(-1) were
      calculated by nonlinear regression analysis of the hyperbola curve. Linear
      regression analysis of the double reciprocal plot revealed k (m) and V (max) of
      80.9 microg mL(-1) and 10.6 microg mL(-1) h(-1), respectively. Time course
      studies displayed about 90% reduction of Cr(VI) at an initial concentration of
      8,000 microg L(-1) in 8 h, with an estimated t (1/2) of 4 h. Data from time
      course analysis of the rate of Cr(VI) bioreduction fitted zero-order model, and
      the kinetic constant k was calculated to be 840 microg L(-1) h(-1). The
      monoculture isolate, Bacillus sp. PB2, strongly reduces Cr(VI) and could be used
      for bioremediation of Cr(VI)-contaminated aquatic and terrestrial environments.

PMID- 18317708
TI  - Graft-versus-host disease and immunosuppression.

PMID- 18317709
TI  - Development and validation of a scale to assess social support in the postpartum
      period.
AB  - The development, reliability, and validity of a new instrument designed to assess
      aspects of social support specifically relevant to the postpartum period, the
      Postpartum Social Support Questionnaire (PSSQ), is described. The PSSQ was
      administered to 126 women at 2, 4, 6, and 12 months postpartum. Results indicate
      that it has high test-retest reliability and internal consistency. Factor
      analyses suggest that the scale consists of four factors: partner support, parent
      support, in-law support, and extended-family and friends support. In addition,
      the PSSQ scores of depressed and nondepressed women were compared at 2, 4, 6, and
      12 months postpartum. Women who met diagnostic criteria for depression at 2
      months postpartum reported less partner support than the nondepressed women at
      each assessment. The instrument appears to be a valid and reliable measure that
      should be useful in studies examining the role of social support in postpartum
      adaptation.

PMID- 18317710
TI  - Effects of a mindfulness-based intervention during pregnancy on prenatal stress
      and mood: results of a pilot study.
AB  - Stress and negative mood during pregnancy increase risk for poor childbirth
      outcomes and postnatal mood problems and may interfere with mother-infant
      attachment and child development. However, relatively little research has focused
      on the efficacy of psychosocial interventions to reduce stress and negative mood
      during pregnancy. In this study, we developed and pilot tested an eight-week
      mindfulness-based intervention directed toward reducing stress and improving mood
      in pregnancy and early postpartum. We then conducted a small randomized trial
      (n=31) comparing women who received the intervention during the last half of
      their pregnancy to a wait-list control group. Measures of perceived stress,
      positive and negative affect, depressed and anxious mood, and affect regulation
      were collected prior to, immediately following, and three months after the
      intervention (postpartum). Mothers who received the intervention showed
      significantly reduced anxiety (effect size, 0.89; p<0.05) and negative affect
      (effect size, 0.83; p<0.05) during the third trimester in comparison to those who
      did not receive the intervention. The brief and nonpharmaceutical nature of this
      intervention makes it a promising candidate for use during pregnancy.

PMID- 18317714
TI  - [Hiatus hernia and recurrence : the Achilles heel of antireflux surgery?].
AB  - Long-term studies show good postoperative results after laparoscopic antireflux
      surgery, but still approximately 10% of patients suffer from new or recurrent
      symptoms of gastroesophageal reflux disease. In the majority of cases the
      symptoms are caused by morphological changes of the fundic wrap or are related to
      the hiatal closure. Closure of the esophageal hiatus is therefore becoming more
      and more the key point of antireflux surgery. The aim of this study was to show
      the problems caused by the esophageal hiatus and to offer possible solutions.
      Therefore 1,201 laparoscopic antireflux procedures and 240 refundoplications
      performed in our department between 1993 and 2007 were analyzed with respect to
      morphologic reasons for failures and the corresponding symptoms. The most common
      morphological reason for complications after surgery was failure of the hiatal
      closure with consecutive intrathoracic migration of the fundic wrap, the so
      called slipped Nissen. In the past the typical problems after open antireflux
      surgery were either that the wrap was too loose, a breakdown of the wrap or a so
      called telescope phenomenon, all caused by failure of the fundic wrap and now a
      rarity since laparoscopic surgery. Even after repeated laparoscopic
      refundoplications the main problem was always the hiatus. This shows the
      importance of the crural closure and the necessity of a specific definition of
      size and form of the hiatus.The aim of this study was to initiate a discussion
      leading to a new definition of the hiatus with the focus on the "hiatal surface
      area" for a better basis for comparison of the published results of antireflux or
      hiatal surgery.

PMID- 18317715
TI  - [Lymph node dissection in papillary and follicular thyroid cancer].
AB  - BACKGROUND: There is still unresolved debate about the optimal surgical
      management of papillary (PTC) and follicular (FTC) thyroid cancer regarding lymph
      node dissection. So far the German guidelines recommend the same extent of
      surgery for both tumors. PATIENTS AND METHODS: This study is based on 626
      patients with PTC and 191 with FTC from a group of 1062 own patients with thyroid
      malignancies. The extent of surgery, tumor size, and pN status were analysed. The
      results were compared with those in the current literature. RESULTS: Tumors < or
      = 20 mm in size were found significantly more often in PTC than FTC (69.6% vs
      28.3%, P<0.05). Positive lymph nodes were found significantly more often in PTC
      than FTC as well (33.2% vs 5.2%, P<0.05). In PTC up to 10 mm and from 11 mm to 20
      mm in size, 16% and 34.4% of patients, respectively, showed positive lymph nodes.
      In FTC positive lymph nodes occurred only in tumors >25 mm. CONCLUSION: Due to
      prevalence and importance of lymph node metastasis differing between PTC and FTC,
      we recommend treating both tumor entities differently. For PTC a more extended
      lymph dissection is necessary, even in tumors < or = 20 mm. In small FTC it seems
      adequate to limit the operation to thyroidectomy without prophylactic lymph
      dissection.

PMID- 18317717
TI  - [Tortuosity and calcification of the splenic artery. More than an additional
      finding].
AB  - Tortuosity of the splenic artery and calcification of the vessel wall are typical
      additional findings on plain abdominal x-ray. The combination of both anomalies
      is common in elderly persons presenting without symptoms of splenic ischemia. Its
      pathogenesis is thought to be multifactorial. In infancy and childhood, the
      splenic artery is stretched in its entire course. A growing difference between
      the length of the vessel and the distance between its origin and the splenic
      hilum gives rise to tortuosity. The artery's proximal segment is involved more
      frequently and more severely than the distal one. The tortuous route of the
      vessel is accentuated by the direction of its major branches, which is roughly
      perpendicular to the main trajectory. Neither tortuosity nor calcification should
      be taken to be risk factors for the comparatively common splenic artery aneurysm.
      Calcific deposits are not confined to the media but are also detected in the
      intima of the vascular wall. Critical narrowings of the lumen arising on the
      calcium deposits are not observed. Calcifying atherosclerosis of the splenic
      artery is comparable to medial sclerosis of the peripheral arteries frequently
      noticed in diabetics and dialysis patients. Only the less important calcification
      of the intima may be attributed to mechanisms of the hydrohemodynamic theory of
      atherosclerosis. The spleen's blood storage capacity may contribute to the
      characteristic age-dependent alterations of the shape and course of the splenic
      artery.

PMID- 18317718
TI  - [Comparison of the effectiveness between long-term instillation of mitomycin C
      and short-term prophylaxis with MMC or bacille Calmette-Guerin. Study of patients
      with non-muscle-invasive urothelial cancer of the urinary bladder].
AB  - BACKGROUND: Adjuvant instillation therapy with chemo- or immunotherapeutic agents
      is an integral component in the treatment of non-muscle-invasive bladder cancer.
      There is, however, no general consensus on the choice of medication and the
      optimal duration of therapy. This multicenter trial compared a long-term
      treatment regimen with mitomycin C (MMC) with two short-term treatment approaches
      with MMC or bacille Calmette-Guerin (BCG) for intermediate-/high-risk bladder
      tumor after transurethral resection. In patients with low-risk bladder tumors,
      the effectiveness of six weekly MMC instillations was determined and compared
      with the results of patients not receiving adjuvant treatment. MATERIAL AND
      METHODS: A total of 495 patients with intermediate-/high-risk bladder tumor
      (recurrent and/or multifocal pTaG1, pTaG2-3, or pT1G1-3) were randomly
      administered either BCG-RIVM 2x108 CFU in six weekly instillations, MMC 20 mg in
      six weekly instillations, or MMC 20 mg in six weekly instillations with
      subsequent monthly instillations for 3 years. A total of 132 low-risk patients
      (first diagnosis of a unifocal pTaG1 bladder tumor) were randomly allocated to
      two treatment arms. In the first arm, 20 mg MMC were instilled weekly six times.
      In the control arm, the patients received no adjuvant therapy. RESULTS: The 3
      year recurrence-free rate in the patients of the intermediate-/high-risk group
      was 65.5% (95% CI: 55.9-73.5%) in the BCG arm and 68.6% (95% CI: 59.9-75.7%) in
      the MMC short-term arm. In the MMC long-term arm, the 3-year recurrence-free rate
      was significantly higher at 86.1% (95% CI: 77.9-91.4%, log-rank test: p=0.001).
      There was no increased toxicity observed with long-term administration of MMC. In
      the low-risk group, the 3-year recurrence-free rate after adjuvant therapy was
      74% (95% CI: 60.0-83.8%) and in the patients receiving no adjuvant treatment 63%
      (95% CI: 46.6-75.5%, corresponding to a hazard ratio of 0.58 (95% CI: 0.28
      1.18%). The difference between the treatment arms was not significant.
      CONCLUSION: Long-term prophylaxis with MMC results in a significantly reduced
      recurrence rate in intermediate-/high-risk bladder cancer with a comparable
      toxicity profile in comparison to short-term MMC or short-term BCG. Our study
      showed no significant decrease of the recurrence rate in low-risk tumors with six
      adjuvant MMC instillations. This treatment approach thus does not represent an
      alternative to early instillation.

PMID- 18317719
TI  - Construction of a potato transcriptome map based on the cDNA-AFLP technique.
AB  - The cDNA-AFLP technique can be used to monitor differential gene expression, but
      also for linkage mapping. Extending previous works, we have now constructed an
      integrated linkage map of the potato transcriptome based on the said technique
      that has a length of around 800 cM and contains nearly 700 transcriptome derived
      fragments (TDFs). At the same time, most of these markers are anchored to the
      bins of a highly saturated reference map in potato, combining in this way the
      information provided by different marker types. Moreover, we detected and
      confirmed an elevated degree of allelic fragments with this marker type, which
      was present in nearly half of all primer combinations and involved around 20% of
      all fragments. These properties were particularly useful to establish anchor
      points for integrating the individual parental linkage maps. Comparative
      expression profiling in different plant materials revealed that only a few
      additional TDFs were obtained which were specific for mature leaves or tubers
      compared to the TDFs present in whole in vitro plants. Since TDF markers are
      derived from coding regions, they generally also represent sequences with a
      biological function. In four case studies, co-migrating TDFs in different Solanum
      wild species always represented potential alleles based on elevated homologies
      among them. Two resistance gene homologs were identified by analysing TDFs, which
      were co-located with known QTLs.

PMID- 18317720
TI  - Association analysis of the IGF1 gene with childhood growth, IGF-1 concentrations
      and type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Insulin-like growth factor-1 is a major childhood growth factor
      and promotes pancreatic islet cell survival and growth in vitro. We hypothesised
      that genetic variation in IGF1 might be associated with childhood growth, glucose
      metabolism and type 1 diabetes risk. We therefore examined the association
      between common genetic variation in IGF1 and predisposition to type 1 diabetes,
      childhood growth and metabolism. MATERIALS AND METHODS: Variants in IGF1 were
      identified by direct resequencing of the exons, exon-intron boundaries and 5' and
      3' regions in 32 unrelated type 1 diabetes patients. A tagging subset of these
      variants was genotyped in a collection of type 1 diabetes families (3,121 parent
      child trios). We also genotyped a previously reported CA repeat in the region 5'
      to IGF1. A subset of seven tag single nucleotide polymorphism (SNPs) that
      captured variants with minor allele frequency (MAF) > or =0.05 was genotyped in
      902 children from the Avon Longitudinal Study of Parents And Children with data
      on growth, IGF-1 concentrations, insulin secretion and insulin action. RESULTS:
      Resequencing detected 27 SNPs in IGF1, of which 11 had a MAF > 0.05 and were
      novel. Variants with MAF > or = 0.10 were captured by a set of four tag-SNPs.
      These SNPs showed no association with type 1 diabetes. In children, global
      variation in IGF1 was weakly associated with IGF-1 concentrations, but not with
      other phenotypes. The CA repeat in the region 5' to IGF1 showed no association
      with any phenotype. CONCLUSIONS/INTERPRETATION: Common genetic variation in IGF1
      alters IGF-1 concentrations but is not associated with growth, glucose metabolism
      or type 1 diabetes.

PMID- 18317721
TI  - Caveats regarding the use of HbA1c for prediction of mean blood glucose.

PMID- 18317722
TI  - Fatty acid-induced mitochondrial uncoupling in adipocytes as a key protective
      factor against insulin resistance and beta cell dysfunction: do adipocytes
      consume sufficient amounts of oxygen to oxidise fatty acids?

PMID- 18317723
TI  - Serum alpha- and gamma-tocopherol concentrations and risk of advanced beta cell
      autoimmunity in children with HLA-conferred susceptibility to type 1 diabetes
      mellitus.
AB  - AIMS/HYPOTHESIS: The aim of our study was to assess the associations of serum
      alpha- and gamma-tocopherol concentrations with the risk of advanced beta cell
      autoimmunity in children with HLA-conferred genetic susceptibility to type 1
      diabetes mellitus. METHODS: A case-control study with 108 cases with advanced
      beta cell autoimmunity and 216 matched control participants nested within the
      birth cohort of the Type 1 Diabetes Prediction and Prevention Project. A serum
      sample for vitamin E analyses was collected from all the children in the cohort
      at the age of 1 year and thereafter at 12 month intervals. For each case-control
      group, all the repeated serum samples up to the age of seroconversion to
      autoantibody positivity in the case were analysed. A conditional logistic
      regression model was used to determine potential associations between
      seroconversion and serum tocopherol concentrations. RESULTS: Serum alpha- or
      gamma-tocopherol concentrations were not significantly associated with the risk
      of advanced beta cell autoimmunity. The odds ratio (95% CI) for micromol/l
      increase in serum concentration of the first-year sample was 0.97 (0.92-1.03) for
      alpha-tocopherol and 1.10 (0.70-1.74) for gamma-tocopherol. However, there was an
      interaction between high values of gamma-tocopherol at the age of 1 year and the
      time of seroconversion (p = 0.024). CONCLUSIONS/INTERPRETATION: It seems unlikely
      that high concentrations of alpha- or gamma-tocopherol protect against advanced
      beta cell autoimmunity in young children.

PMID- 18317724
TI  - The impact of diabetes on prescription drug costs: the population-based Turin
      study.
AB  - AIMS/HYPOTHESIS: The aim of our study was to compare prescription drug costs in
      diabetic and non-diabetic individuals in a large population-based Italian cohort
      covered by the National Health System. METHODS: We identified diabetic residents
      in Turin on 31 July 2003 through multiple independent data sources (diabetes
      registry, hospital discharges and prescriptions data sources). All prescriptions
      registered in the 12 month period 1 August 2003 to 31 July 2004 were examined to
      compare prevalence of treatment and costs in diabetic (n = 33,797) and non
      diabetic individuals (n = 863,876). A log-linear model was employed to estimate
      age- and sex-adjusted ratios of costs. RESULTS: Costs per person per year were
      830.90euros in diabetic patients and 182.80euros in non-diabetic individuals (age
      and sex-adjusted rate ratio 2.8, 95% CI 2.7-2.9). Diabetes treatment accounted
      for 18.5% of the total cost. Compared with non-diabetic individuals, the excess
      of expenditure was particularly high in diabetic patients aged <45 years (rate
      ratio 9.3), in those with type 1 diabetes (rate ratio 7.7) and in insulin users
      (rate ratio 4.8). The cost of diet-treated patients was similar to those treated
      with oral drugs. Diabetes was associated with an increased prevalence of
      treatment for most drug categories; one-third of the diabetic cohort received ACE
      inhibitors, anti-thrombotic drugs and statins. CONCLUSIONS/INTERPRETATION: This
      population-based study shows that diabetes has a great impact on prescription
      drug costs, independently of main confounders, particularly in insulin-treated
      patients, suggesting that a wide range of comorbidities affect their health.
      Costs are expected to further increase if the transferability of knowledge
      provided by evidence-based guidelines on diabetic patients is completed over the
      coming years.

PMID- 18317725
TI  - Marked temporal increase in the incidence of type 1 and type 2 diabetes among
      young adults in Finland.

PMID- 18317726
TI  - Impaired fasting glycaemia vs impaired glucose tolerance: similar impairment of
      pancreatic alpha and beta cell function but differential roles of incretin
      hormones and insulin action.
AB  - AIMS/HYPOTHESIS: The impact of strategies for prevention of type 2 diabetes in
      isolated impaired fasting glycaemia (i-IFG) vs isolated impaired glucose
      tolerance (i-IGT) may differ depending on the underlying pathophysiology. We
      examined insulin secretion during OGTTs and IVGTTs, hepatic and peripheral
      insulin action, and glucagon and incretin hormone secretion in individuals with i
      IFG (n = 18), i-IGT (n = 28) and normal glucose tolerance (NGT, n = 20). METHODS:
      Glucose tolerance status was confirmed by a repeated OGTT, during which
      circulating insulin, glucagon, glucose-dependent insulinotrophic polypeptide
      (GIP) and glucagon-like peptide-1 (GLP-1) levels were measured. A euglycaemic
      hyperinsulinaemic clamp with [3-3H]glucose preceded by an IVGTT was performed.
      RESULTS: Absolute first-phase insulin secretion during IVGTT was decreased in i
      IFG (p = 0.026), but not in i-IGT (p = 0.892) compared with NGT. Hepatic insulin
      sensitivity was normal in i-IFG and i-IGT individuals (p > or = 0.179).
      Individuals with i-IGT had peripheral insulin resistance (p = 0.003 vs NGT), and
      consequently the disposition index (DI; insulin secretion x insulin sensitivity)
      during IVGTT (DI(IVGTT))) was reduced in both i-IFG and i-IGT (p < 0.005 vs NGT).
      In contrast, the DI during OGTT (DI(OGTT)) was decreased only in i-IGT (p <
      0.001), but not in i-IFG (p = 0.143) compared with NGT. Decreased levels of GIP
      in i-IGT (p = 0.045 vs NGT) vs increased levels of GLP-1 in i-IFG (p = 0.013 vs
      NGT) during the OGTT may partially explain these discrepancies. Basal and post
      load glucagon levels were significantly increased in both i-IFG and i-IGT
      individuals (p < or = 0.001 vs NGT). CONCLUSIONS/INTERPRETATION: We propose that
      differentiated preventive initiatives in prediabetic individuals should be
      tested, targeting the specific underlying metabolic defects.

PMID- 18317727
TI  - Increasing overall physical activity and aerobic fitness is associated with
      improvements in metabolic risk: cohort analysis of the ProActive trial.
AB  - AIMS/HYPOTHESIS: Our aim was to examine the association between change in
      physical activity energy expenditure (PAEE), total body movement (counts per day)
      and aerobic fitness (maximum oxygen consumption [VO2max] over 1 year and
      metabolic risk among individuals with a family history of diabetes. METHODS:
      Three hundred and sixty-five offspring of people with type 2 diabetes underwent
      measurement of energy expenditure (PAEE measured using the flex heart rate
      method), total body movement (daily activity counts from accelerometry data),
      [VO2max] predicted from a submaximal graded treadmill exercise test and
      anthropometric and metabolic status at baseline and 1 year (n = 321) in the
      ProActive trial. Clustered metabolic risk was calculated by summing standardised
      values for waist circumference, fasting triacylglycerol, insulin and glucose,
      blood pressure and the inverse of HDL-cholesterol. Linear regression was used to
      quantify the association between changes in PAEE, total body movement and fitness
      and clustered metabolic risk at follow-up. RESULTS: Participants increased their
      activity by 0.01 units PAEE kJ kg(-1) day(-1) over 1 year. Total body movement
      increased by an average of 9,848 counts per day. Change in total body movement
      (beta = -0.066, p = 0.004) and fitness (beta = -0.056, p = 0.003) was associated
      with clustered metabolic risk at follow-up, independently of age, sex, smoking
      status, socioeconomic status and baseline metabolic score.
      CONCLUSIONS/INTERPRETATION: Small increases in activity and fitness were
      associated with a reduction in clustered metabolic risk in this cohort of
      carefully characterised at-risk individuals. Further research to quantify the
      reduction in risk of type 2 diabetes associated with feasible changes in these
      variables should inform preventive interventions.

PMID- 18317728
TI  - Beta cell mass in diabetes: a realistic therapeutic target?
AB  - Beta cell deficiency underlies both type 1 and type 2 diabetes, and restoration
      or replacement of beta cell function is therefore the logical long-term solution
      to therapy. This review sets out to describe the defects in beta cell mass and
      function in both forms of diabetes, summarises current understanding of the
      underlying causes of beta cell death, and the methodological limitations of
      determining beta cell mass in vivo. Finally, the potential effects of current and
      future treatment regimens on beta cell mass and turnover are considered.

PMID- 18317729
TI  - LR-90 prevents dyslipidaemia and diabetic nephropathy in the Zucker diabetic
      fatty rat.
AB  - AIMS/HYPOTHESIS: Previous studies have shown that LR-90, a new inhibitor of AGE
      formation, prevented the development of experimental type 1 diabetic nephropathy.
      In this study, we examined the effects of LR-90 in the Zucker diabetic fatty
      (ZDF) rat, a model of type 2 diabetes and metabolic syndrome, and investigated
      the mechanisms by which it may protect against renal injury. METHODS: Male ZDF
      rats were treated without or with LR-90 from age 13 to 40 weeks. Metabolic and
      kidney functions and renal histology were evaluated. AGE accumulation and the
      production of the receptor for AGE (AGER) were measured. Profibrotic growth
      factors, extracellular matrix proteins and intracellular signalling pathways
      associated with glomerular and tubular damage were also analysed. RESULTS: LR-90
      dramatically reduced plasma lipids in ZDF rats, with only modest effects on
      hyperglycaemia. Renal AGE, AGER and lipid peroxidation were all attenuated by LR
      90. LR-90 significantly retarded the increase in albuminuria and proteinuria.
      This was associated with reduction in glomerulosclerosis and tubulointerstitial
      fibrosis, concomitant with marked inhibition of renal overproduction of TGF
      beta1, connective tissue growth factor, fibronectin and collagen IV.
      Additionally, LR-90 downregulated the activation of key mitogen-activated protein
      kinases (MAPKs) and nuclear factor kappa B (NF-kappaB) in the renal cortex.
      CONCLUSIONS/INTERPRETATION: These results support our earlier studies on the
      renoprotective effects of LR-90 on type 1 diabetic nephropathy and provide
      further evidence that LR-90, an AGE inhibitor with pleiotrophic effects, may also
      be beneficial for the prevention of type 2 diabetic nephropathy, where multiple
      risk factors, such as hyperglycaemia, dyslipidaemia, obesity, insulin resistance
      and hypertension, contribute to renal injury.

PMID- 18317730
TI  - [Autologous chondrocyte transplantation in the treatment of articular cartilage
      lesions of the talus].
AB  - In contrast to the knee joint, autologous chondrocyte transplantation (ACT) is
      rarely used for treating articular cartilage lesions in the ankle joint. Matrix
      associated autologous chondrocyte transplantation (MACT) with the use of
      biomaterials as cell carriers has facilitated operative application and fixation
      within the lesion. We have gained experience in the use of two different MACT
      techniques. According to the Hannover scoring system for the ankle and visual
      analog scores, results improved significantly (p<or=0.001) after MACT with the
      Hyalograft C in nine ankles at a mean follow-up of 3.7 years (range 2.6-4.8
      years). All patients had undergone prior operative treatment for the cartilage
      lesion. Two patients were rated as excellent and seven as good. According to the
      ICRS cartilage repair assessment score, the transplanted areas were rated nearly
      normal (grade II) in seven patients who underwent undergone repeat arthroscopy.
      Magnetic resonance imaging revealed that in the majority of cases, filling of the
      defect was accomplished with a nonhomogeneous surface and structure of the graft.
      The use of a purely arthroscopically applicable three-dimensional MACT (ARTROcell
      3D) with chondrospheres further facilitates the process and reduces operative
      morbidity. We have included eight patients in a prospective study so far. Six
      patients had undergone prior operative treatment for the cartilage lesion. In two
      cases, culturing of the cells failed for unexplained reasons; therefore, only six
      patients finally received the MACT with chondrospheres, and only four patients
      were evaluated at a 6-month follow-up examination. Thus, valid results cannot be
      reported. In revision cases, MACT is suggested to be a reliable alternative for
      treating articular cartilage lesions of the talus, but longer-term results in
      more patients remain to be evaluated.

PMID- 18317731
TI  - On the way towards eradication of catheter-related infections!

PMID- 18317732
TI  - Influence of insertion site on central venous catheter colonization and
      bloodstream infection rates.
AB  - OBJECTIVE: To compare colonization and catheter-related bloodstream infection (CR
      BSI) rates among three insertion sites (subclavian, internal jugular, femoral)
      used for central venous catheter (CVC) placement. DESIGN: Twenty-four-month
      prospective study, with relative effects analyzed by Cox proportional hazards
      regression. SETTING: Eight-bed intensive care unit. PATIENTS: Four hundred and
      ten critically ill patients requiring CVC placement. MEASUREMENTS AND RESULTS:
      All short-term multi-lumen CVCs, including antimicrobial-coated devices, were
      studied with management standardized. Six hundred and five CVCs (4,040 catheter
      days) were analyzed. Colonization and CR-BSI incidence were, respectively, 15.1
      (95% CI 13.5-21.0) and 1.8 (95% CI 1.2-4.2) per 1,000 catheter-days. Colonization
      was higher at the internal jugular (HR 3.64; 95% CI 1.32-10.00; p=0.01) and
      femoral (HR 5.15; 95% CI 1.82-14.51; p=0.004) sites than at the subclavian site.
      The femoral site carried a greater risk of being colonized by non-S. epidermidis
      species than the subclavian and internal jugular sites combined (HR 4.15; 95% CI
      1.79-9.61; p=0.001). CVCs inserted in the Department of Emergency Medicine were
      more colonized than those inserted in the ICU or operating room (HR 2.66; 95% CI
      1.27-5.56; p=0.01), and CVCs were less colonized in females than in males (HR
      0.49; 95% CI 0.26-0.89; p=0.02). No difference in CR-BSI rates was noted between
      the three sites. CONCLUSIONS: Colonization was lowest at the subclavian site.
      Regional differences exist with respect to type of pathogen isolated.
      Colonization was influenced by insertion location and gender. The incidence of CR
      BSI was not different.

PMID- 18317733
TI  - Disparity between skin perfusion and sublingual microcirculatory alterations in
      severe sepsis and septic shock: a prospective observational study.
AB  - OBJECTIVE: Measurement of central-to-toe temperature difference has been
      advocated as an index of severity of shock and as a guide for circulatory therapy
      in critically ill patients. However, septic shock, in contrast to other forms of
      shock, is associated with a distributive malfunction resulting in a disparity
      between vascular compartments. Although this disparity has been established
      between systemic and microcirculatory parameters, it is unclear whether such
      disparity exists between skin perfusion and microcirculation. To test this
      hypothesis of disparity, we simultaneously measured parameters of the two
      vascular compartments, in the early phase of sepsis. DESIGN: Prospective
      observational study in patients with severe sepsis/septic shock in the first 6 h
      of ICU admission. Simultaneous measurements of central-to-toe temperature
      difference and sublingual microcirculatory orthogonal polarization spectral
      imaging, together with parameters of systemic hemodynamics. SETTING: 22 bed mixed
      ICU in a tertiary teaching hospital. PATIENTS: 35 consecutive patients in a 12
      month period. MEASUREMENTS AND RESULTS: In 35 septic patients and a median APACHE
      II score of 20, no correlation between central-to-toe temperature gradient and
      microvascular flow index was observed (r (s) = -0.08, p =0.65). Also no
      significant correlation between temperature gradient/microvascular flow index and
      systemic hemodynamic parameters could be demonstrated. CONCLUSIONS: During the
      early phase of resuscitated severe sepsis and septic shock there appears to be no
      correlation between sublingual microcirculatory alterations and the central-to
      toe temperature difference. This finding adds to the concept of a dispersive
      nature of blood flow under conditions of sepsis between microcirculatory and
      systemic hemodynamics.

PMID- 18317734
TI  - Relevance of animal models to human eating disorders and obesity.
AB  - BACKGROUND AND RATIONALE: This review addresses the role animal models play in
      contributing to our knowledge about the eating disorders anorexia nervosa (AN)
      and bulimia nervosa (BN) and obesity. OBJECTIVES: Explore the usefulness of
      animal models in complex biobehavioral familial conditions, such as AN, BN, and
      obesity, that involve interactions among genetic, physiologic, psychological, and
      cultural factors. RESULTS AND CONCLUSIONS: The most promising animal model to
      mimic AN is the activity-based anorexia rodent model leading to pathological
      weight loss. The paradigm incorporates reward elements of the drive for activity
      in the presence of an appetite and allows the use of genetically modified
      animals. For BN, the sham-feeding preparation in rodents equipped with a gastric
      fistula appears to be best suited to reproduce the postprandial emesis and the
      defects in satiety. Animal models that incorporate genes linked to behavior and
      mood may clarify biobehavioral processes underlying AN and BN. By contrast, a
      relative abundance of animal models has contributed to our understanding of human
      obesity. Both environmental and genetic determinants of obesity have been modeled
      in rodents. Here, we consider single gene mutant obesity models, along with
      models of obesigenic environmental conditions. The contributions of animal models
      to obesity research are illustrated by their utility for identifying genes linked
      to human obesity, for elucidating the pathways that regulate body weight and for
      the identification of potential therapeutic targets. The utility of these models
      may be further improved by exploring the impact of experimental manipulations on
      the behavioral determinants of energy balance.

PMID- 18317735
TI  - The postweaning social isolation in C57BL/6 mice: preferential vulnerability in
      the male sex.
AB  - INTRODUCTION: Social deprivation during early life can severely affect mental
      health later in adulthood, leading to the development of behavioural traits
      associated with several major psychiatric disorders including schizophrenia. This
      has led to the application of social isolation in laboratory animals to model the
      impact of environmental factors on the aetiopathology of schizophrenia. However,
      controversy exists over the precise behavioural profile and the robustness of
      some of the reported effects of social isolation rearing. MATERIALS AND METHODS:
      Here, we evaluated the efficacy of postweaning social isolation to induce
      schizophrenia-related behavioural deficits in C57BL/6 mice of both sexes.
      RESULTS: The effects of social isolation clearly differed between sexes: isolated
      male but not female mice exhibited multiple habituation deficits and enhanced
      locomotor reaction to amphetamine. DISCUSSION: The preferential vulnerability in
      the male sex corresponds well with the earlier disease onset and poorer prognosis
      in male relative to female schizophrenic patients. In contrast, we observed no
      evidence for a disruption of sensorimotor gating in the prepulse inhibition
      paradigm despite the efficacy of social isolation to alter startle reactivity.
      With both success and failure in the induction of schizophrenia-related
      endophenotypes, the present study thus provides important characterizations and
      qualifications to the application of the social isolation model in mice.
      CONCLUSIONS: We conclude that social isolation in mice represents a valuable tool
      for the examination of candidate genes within the context of the "two-hit"
      hypothesis of the aetiological processes in schizophrenia.

PMID- 18317736
TI  - A whole-cell assay for the high throughput screening of calmodulin antagonists.
AB  - Cell-based screening systems for pharmaceuticals are desired over molecular
      biosensing systems because of the information they provide on toxicity and
      bioavailability. However, the majority of sensing systems developed are molecular
      biosensing type screening systems and cannot be easily adapted to cell-based
      screening. In this study, we demonstrate that protein-based molecular sensing
      systems that employ a fluorescent protein as a signal transducer are amenable to
      cell-based sensing by expressing the protein molecular sensing system in the cell
      and employing these cells for screening of desired molecules. To achieve this, we
      expressed a molecular sensing system based on the fusion protein of calmodulin
      (CaM) and enhanced green fluorescent protein (EGFP) in bacterial cells, and
      utilized these cells for the screening of CaM antagonists. In the presence of
      Ca(2+), CaM undergoes a conformational change exposing a hydrophobic pocket that
      interacts with CaM-binding proteins, peptides, and drugs. This conformational
      change induced in CaM leads to a change in the microenvironment of EGFP,
      resulting in a change in its fluorescence intensity. The observed change in
      fluorescence intensity of EGFP can be correlated to the concentration of the
      analyte present in the sample. Dose-response curves for various tricyclic
      antidepressants were generated using cells containing CaM-EGFP fusion protein.
      Additionally, we demonstrate the versatility of our system for studying protein
      protein interactions by using cells to study the binding of a peptide to CaM. The
      study showed that the CaM-EGFP fusion protein within the intact cells responds
      similarly to that of the isolated fusion protein, hence eliminating the need for
      any isolation and purification steps. We have demonstrated that this system can
      be used for the rapid screening of various CaM antagonists that are potential
      antipsychotic drugs.

PMID- 18317737
TI  - Fast purification of trace vitellogenin from Chinese rare minnow using protein A
      immobilized antibody.
AB  - Vitellogenin (Vtg) is a highly responsive biomarker for environmental exposure to
      various estrogenically active compounds. Here we present a simple, fast, mild,
      and stable immobilization of anti-Vtg antibody, and demonstrate its powerful
      applications for preconcentration and purification of fish Vtg proteins, allowing
      for the monitoring and screening of environmental exposure to estrogenically
      active compounds. In this immobilization method, rabbit antiserum containing a
      specific polyclonal antibody against Vtg was directly immobilized on an antibody
      binding Staphylococcal protein A matrix (SpA) without the need for prior
      purification. Under the unique elution conditions, the Vtg protein can be eluted
      out alone without any leaked specific antibody. The developed method was further
      used to purify Vtg from whole-body homogenate of Chinese rare minnow. Compared
      with previous purification methods, the isolated Vtg fraction by this method
      displays higher purity and well-preserved structure integrity. Moreover, our
      method is eight times faster. The simple one-step protein A-based specific
      antibody immobilization and its associated elution strategy may be extended to a
      number of antibodies for various application purposes, highlighting the paramount
      advantages over traditional immunoprecipitation and covalent immobilization of
      antibodies, and suggesting a wide range of promising applications in
      environmental monitoring and proteome analysis.

PMID- 18317738
TI  - Comparison of methods with respect to efficiencies, recoveries, and quantitation
      of mercury species interconversions in food demonstrated using tuna fish.
AB  - Eight different analytical extraction procedures commonly used to extract mercury
      species from biological samples were evaluated by analyzing Tuna Fish Tissue
      Certified Reference Material (ERM-CE464) certified for the content of total
      mercury and methylmercury. Speciated isotope dilution mass spectrometry (SIDMS;
      US Environmental Protection Agency's method 6800) was utilized to evaluate and
      effectively compensate for potential errors during measurement and accurately
      quantify mercury species using all the extraction methods. SIDMS was used to
      accurately evaluate species transformations during sample pretreatment,
      preparation and analysis protocols. The extraction methods tested in this paper
      were based on alkaline extraction with KOH or tetramethylammonium hydroxide; acid
      leaching with HCl, HNO(3) or CH(3)COOH; extraction with L: -cysteine
      hydrochloride; and enzymatic digestion with protease XIV. Detection of total
      mercury and mercury species from all extraction methods was carried out by
      inductively coupled plasma mass spectrometry (ICP-MS) and high-performance liquid
      chromatography-ICP-MS, respectively. Microwave-assisted extraction and ultrasound
      assisted extraction were found to be the most efficient alkaline digestion
      protocols that caused the lowest levels of transformation of mercury species (6%
      or less). Extraction with 5 M HCl or enzymatic digestion with protease resulted
      in the second-highest extraction efficiency, with relatively lower transformation
      of methylmercury to inorganic mercury (3 and 1.4%, respectively). Despite
      frequent use of acid leaching for the extraction of mercury species from tuna
      fish samples, the lowest extraction efficiencies and the highest mercury species
      transformation were obtained when microwave-assisted extraction with 4 M HNO(3)
      or CH(3)COOH was used. Transformations as high as 30% were found using some
      literature protocols; however, all the extractions tested produced accurate
      quantitation when corrected in accordance with the SIDMS method standardized in
      the US Environmental Protection Agency's method 6800. [figure: see text]

PMID- 18317739
TI  - PowerSlicing to determine fluorescence lifetimes of water-soluble organic matter
      derived from soils, plant biomass, and animal manures.
AB  - Time-resolved fluorescence spectroscopy was used to characterize water-soluble
      organic matter (WSOM) which plays an important role in soil ecosystem processes.
      WSOM was extracted from plant biomass, animal manures, and soils from controlled
      cropping systems studies with known histories of organic amendments. Lifetime
      constants were derived using the multi-way PowerSlicing method which provides a
      non-iterative, multi-exponential fitting of decay profiles. The lifetimes
      obtained by PowerSlicing were not significantly different from those obtained
      using the traditional discrete components analysis. The three components
      attributed to WSOM had lifetimes of 0.38 +/- 0.14, 2.11 +/- 0.72, and 7.08 +/-
      1.18 ns which are in agreement with previous lifetimes reported for humic
      substances. This study provides further support for the new paradigm for the
      structure of soil organic matter where the organic matter is composed of low
      molecular-weight components held together by hydrogen bonding and hydrophobic
      interactions.

PMID- 18317740
TI  - Nanoparticle: is it promising in capillary electrophoresis?

PMID- 18317741
TI  - Application of LC and GC hyphenated with mass spectrometry as tool for
      characterization of unknown derivatives of isoflavonoids.
AB  - Polyphenols belonging to the class of secondary metabolites of plants and
      microorganisms play an important role as bioactive food constituents as well as
      contaminants. Structure elucidation of polyphenols in plant extracts or
      polyphenol metabolites, especially those arising during biotransformation, still
      represents a challenge for analytical chemistry. Various approaches have been
      proposed to utilize fragmentation reactions in connection with mass spectrometry
      (MS) for structural considerations on polyphenolic targets. We compiled and
      applied specific liquid chromatography (LC)-electrospray ionization in positive
      mode [ESI(+)]-tandem MS (MS/MS) and gas chromatography (GC)-(electron impact, EI)
      MS/MS fragmentation reactions with a special focus on the analysis of
      isoflavones, whereby this technique was also found to be extendable to determine
      further polyphenols. For ESI(+)-MS the basic retro-Diels-Alder (rDA)
      fragmentation offers information about the substitution pattern in the A- and B
      rings of flavonoids and the elimination of a protonated 4-methylenecyclohexa-2,5
      dienone (m/z = 107) fragment can be used as a diagnostic tool for many
      isoflavanones. For GC-(EI)-MS/MS analysis after derivatization of the analytes to
      their trimethylsilyl ethers, the elimination of methyl radicals,
      tetramethylsilane groups or the combined loss of two methyl groups can be shown
      to be specific for certain substitution patterns in polyphenols. The
      applicability of the fragmentation reactions presented is demonstrated
      exemplarily for three derivatives of the isoflavone irilone. With the help of
      these fragmentation reactions of the two MS techniques combined, a reliable
      identification of polyphenols is possible. Especially in such cases where NMR
      cannot be utilized owing to low analyte amounts being available or prior to
      purification, valuable information can be obtained.

PMID- 18317742
TI  - Induction of muscle cramps by nociceptive stimulation of latent myofascial
      trigger points.
AB  - The aim of this present study is to test the hypothesis that nociceptive
      stimulation of latent myofascial trigger points (MTrPs) increases the occurrence
      of local muscle cramps. Nociceptive muscle stimulation was obtained by a bolus
      injection of glutamate (0.1 ml, 0.5 M) into a latent MTrP and a control point (a
      non-MTrP) located in the right or left gastrocnemius medialis muscles in 14
      healthy subjects. A bolus of isotonic saline (0.9%, 0.1 ml) injection served as a
      control. The injections were guided by intramuscular electromyography (EMG)
      showing resting spontaneous electrical activity at a latent MTrP and no such
      activity at a non-MTrP. Intramuscular and surface EMG activities in the
      gastrocnemius medialis muscle were recorded pre-, during-, and post-injection for
      a period of 8 min to monitor the occurrence of muscle cramps, which are
      characterized by a brief episodic burst of high levels of EMG activity. The
      results showed that glutamate and isotonic saline injections into the latent
      MTrPs induced higher peak pain intensity than into the non-MTrPs (both P < 0.05).
      Glutamate injection induced higher peak pain intensity than isotonic saline
      injection into either latent MTrPs or non-MTrPs (both P < 0.05). Muscle camps
      were observed in 92.86% of the subjects following glutamate injection into the
      latent MTrPs, but not into the non-MTrPs (P < 0.001). No muscle cramps were
      recorded following isotonic saline injection into either the latent MTrPs or the
      non-MTrPs. These results suggest that latent MTrPs could be involved in the
      genesis of muscle cramps. Focal increase in nociceptive sensitivity at MTrPs
      constitutes one of the mechanisms underlying muscle cramps.

PMID- 18317743
TI  - Relationship between the velocity of illusory hand movement and strength of MEG
      signals in human primary motor cortex and left angular gyrus.
AB  - We studied the relationship between the velocity of movement illusion and the
      activity level of primary motor area (M1) and of the left angular gyrus (AG) in
      humans. To induce illusory movement perception, we applied co-vibration at
      different frequencies on tendons of antagonistic muscle groups. Since it is well
      established that the velocity of illusory movement is related to the difference
      in vibration frequency applied to two antagonistic muscles, we compared
      magnetoencephalography (MEG) signals recorded in two conditions of co-vibration:
      in the "fast illusion" condition a frequency difference of 80 Hz was applied on
      the tendons of the right wrist extensor and flexor muscle groups, whereas in the
      "slow illusion" condition a frequency difference of 40 Hz was applied on the same
      muscle groups. The dipole strength, reflecting the activity level of structures,
      was measured over M1 and the left AG in two different time-periods: 0-400 and 400
      800 ms in each condition. Our results showed that the activity level of the AG
      was similar in both conditions whatever the time-period, whereas the activity
      level of M1 was higher in the "fast illusion" condition compared to the "slow
      illusion" condition from 400 ms after the vibration onset only. The data suggest
      that the two structures differently contributed to the perception of illusory
      movements. Our hypothesis is that M1 would be involved in the coding of cinematic
      parameters of the illusory movement but not the AG.

PMID- 18317744
TI  - A mismatch process in brief delayed matching-to-sample task: an fMRI study.
AB  - Our previous ERP studies have consistently demonstrated that a negativity N270
      elicited by incongruent information in visual S1-S2 matching task represents a
      type of conflict process, which is distinct from that represented by the classic
      conflict task or other negative components in delayed matching-to-sample stimulus
      presentation patterns, since the inter-stimulus interval between S1 and S2 was
      presented as shorter as 500 ms. The N270 component of ERP was shown to reflect
      conflict processing during the simple working memory operations. In the present
      study, a functional MRI (fMRI) was used to investigate the visuospatial
      characteristics of brain activation associated with the task eliciting N270. The
      fMRI data showed an increased activation in the right anterior cingulate cortex
      (ACC, BA 24) and right dorsolateral prefrontal cortex (DLPFC, BA 46), and
      activation biased to the left occipitotemporal cortex (BA 37) in the incongruent
      condition. It is suggested that the greater activations of the right ACC coupling
      with right DLPFC to incongruent task reflect functional efficiency of the right
      cingulo-prefrontal network during the brief visual delayed period discrimination
      performance and mismatched information processing.

PMID- 18317745
TI  - Epidermoid cyst of the spleen.

PMID- 18317746
TI  - Monitoring the assembly of antibody-binding membrane protein arrays using
      polarised neutron reflection.
AB  - Protein arrays are used in a wide range of applications. The array described here
      binds IgG antibodies, produced in rabbit, to gold surfaces via a scaffold
      protein. The scaffold protein is a fusion of the monomeric E. coli porin outer
      membrane protein A (OmpA) and the Z domain of Staphylococcus aureus protein A.
      The OmpA binds to gold surfaces via a cysteine residue in a periplasmic turn and
      the Z domain binds immunoglobulins via their constant region. Polarised Neutron
      Reflection is used to probe the structure perpendicular to the gold surface at
      each stage of the assembly of the arrays. Polarised neutrons are used as this
      provides a means of achieving extra contrast in samples having a magnetic metal
      layer under the gold surface. This contrast is attained without resorting to
      hydrogen/deuterium exchange in the biological layer. Polarised Neutron Reflection
      allows for the modelling of many and complex layers with good fits. The total
      thickness of the biological layer immobilised on the gold surface is found to be
      187 A and the layer can thus far be separated into its lipid, protein and solvent
      parts.

PMID- 18317747
TI  - Photocatalytic antimicrobial activity of thin surface films of TiO(2), CuO and
      TiO (2)/CuO dual layers on Escherichia coli and bacteriophage T4.
AB  - TiO(2)-coated surfaces are increasingly studied for their ability to inactivate
      microorganisms. The activity of glass coated with thin films of TiO(2), CuO and
      hybrid CuO/TiO(2) prepared by atmospheric Chemical Vapour Deposition (Ap-CVD) and
      TiO(2) prepared by a sol-gel process was investigated using the inactivation of
      bacteriophage T4 as a model for inactivation of viruses. The chemical oxidising
      activity was also determined by measuring stearic acid oxidation. The results
      showed that the rate of inactivation of bacteriophage T4 increased with
      increasing chemical oxidising activity with the maximum rate obtained on highly
      active sol-gel preparations. However, these were delicate and easily damaged
      unlike the Ap-CVD coatings. Inactivation rates were highest on CuO and CuO/TiO(2)
      which had the lowest chemical oxidising activities. The inactivation of T4 was
      higher than that of Escherichia coli on low activity surfaces. The combination of
      photocatalysis and toxicity of copper acted synergistically to inactivate
      bacteriophage T4 and retained some self-cleaning activity. The presence of
      phosphate ions slowed inactivation but NaCl had no effect. The results show that
      TiO(2)/CuO coated surfaces are highly antiviral and may have applications in the
      food and healthcare industries.

PMID- 18317748
TI  - Functionality of a Bacillus cereus biological agent in response to physiological
      variables encountered in aquaculture.
AB  - The potential of a Bacillus cereus isolate (NRRL 100132) as a biological agent
      for aquaculture has been demonstrated in vitro and in vivo. The functionality of
      this isolate across a range of physiological conditions, including salinity, pH
      and temperature, based on rearing of high-value ornamental Cyprinus carpio, was
      investigated. Temperature had a significant influence on germination, specific
      growth rate and increase in cell number of B. cereus in shake-flask cultures,
      whilst salinity and pH did not have a measurable effect on growth. Controlled
      studies in bioreactors and modelling of the data to the Arrhenius function
      indicated the existence of high and low growth temperature domains. The rates of
      pathogenic Aeromonas hydrophila suppression and decrease in waste ion
      concentrations (ammonium, nitrite, nitrate and phosphate) were translated into a
      linear predictive indicator of efficacy of the B. cereus isolate at different
      temperatures. The present study confirmed the robustness of the B. cereus isolate
      (NRRL 100132) as a putative biological agent for aquaculture and further
      demonstrated a novel method for the assessment of in vitro biological efficacy as
      a function of temperature.

PMID- 18317749
TI  - Synergistic action of rapid chilling and nisin on the inactivation of Escherichia
      coli.
AB  - The effect of rapid and slow chilling on survival and nisin sensitivity was
      investigated in Escherichia coli. Membrane permeabilization induced by cold shock
      was assessed by uptake of the fluorescent dye 1-N-phenylnapthylamine. Slow
      chilling (2 degrees C min(-1)) did not induce transient susceptibility to nisin.
      Combining rapid chilling (2,000 degrees C min(-1)) and nisin causes a dose
      dependent reduction in the population of cells in both exponential and stationary
      growth phases. A reduction of 6 log of exponentially growing cells was achieved
      with rapid chilling in the presence of 100 IU ml(-1) nisin. Cells were more
      sensitive if nisin was present during stress. Nevertheless, addition of nisin to
      cell suspension after the rapid chilling produced up to 5 log of cell
      inactivation for exponentially growing cells and 1 log for stationary growing
      cells. This suggests that the rapid chilling strongly damaged the cell membrane
      by disrupting the outer membrane barrier, allowing the sensitization of E. coli
      to nisin post-rapid chilling. Measurements of membrane permeabilization showed a
      good correlation between the membrane alteration and nisin sensitivity.
      Application involving the simultaneous treatment with nisin and rapid cold shock
      could thus be of value in controlling Gram negatives, enhancing microbiological
      safety and stability.

PMID- 18317750
TI  - Mining Xanthomonas and Streptomyces genomes for new pectinase-encoding sequences
      and their heterologous expression in Escherichia coli.
AB  - Microbial genome sequencing has left a legacy of annotated yet uncharacterized
      genes or open reading frames, activities that may have useful applications in
      health and/or the environment. We are interested in the discovery and
      characterization of potentially new pectinolytic activities for the enzymatic
      retting of natural bast fibers such as hemp and flax. A highlight in this study
      is the discovery of a cold-active pectate lyase among five pectate-lyase-encoding
      sequences and two polygalacturonase-encoding sequences that we have cloned from
      the genomes of Xanthomonas campestris pv. campestris and Streptomyces coelicolor
      A3(2). Heterologous expression of these sequences as active pectate lyases and
      polygalacturonases required their subcloning in Escherichia coli Rosetta cells.
      The most active recombinant pectate lyase (XcPL NP_638163), a cold-active pectate
      lyase (XcPL NP_636037), and a polygalacturonase (XcPG NP_638805) were purified to
      near homogeneity and their kinetic parameters were determined. A significant
      amount of pectin degradation products was shown to be released by the two pectate
      lyases but not the polygalacturonase when hemp fiber pectin was used as
      substrate. Results of this study showed that genome data mining, besides an
      economical approach to new gene acquisition, may uncover new findings such as the
      discovery of a cold-active pectate-lyase-encoding sequence from X. campestris, a
      mesophilic microorganism.

PMID- 18317751
TI  - Clavatol and patulin formation as the antagonistic principle of Aspergillus
      clavatonanicus, an endophytic fungus of Taxus mairei.
AB  - Many endophytic fungi are known to protect plants from plant pathogens, but the
      antagonistic mechanism has rarely been revealed. In this study, we wished to
      learn whether an endophytic Aspergillus sp., isolated from Taxus mairei, would
      indeed produce bioactive components, and if so whether (a) they would antagonize
      plant pathogenic fungi; and (b) whether this Aspergillus sp. would produce the
      compound also under conditions of confrontation with these fungi. The endophytic
      fungal strain from T. mairei was identified as Aspergillus clavatonanicus by
      analysis of morphological characteristics and the sequence of the internal
      transcribed spacers (ITS rDNA) of rDNA. When grown in surface culture, the fungus
      produced clavatol (2',4'-dihydroxy-3',5'-dimethylacetophenone) and patulin (2
      hydroxy-3,7-dioxabicyclo [4.3.0]nona-5,9-dien-8-one), as shown by shown by NMR,
      MS, X-ray, and EI-MS analysis. Both exhibited inhibitory activity in vitro
      against several plant pathogenic fungi, i.e., Botrytis cinerea, Didymella
      bryoniae, Fusarium oxysporum f. sp. cucumerinum, Rhizoctonia solani, and Pythium
      ultimum. During confrontation with P. ultimum, A. clavatonanicus antagonized its
      growth of P. ultimum, and both clavatol as well as patulin were formed as the
      only bioactive components, albeit with different kinetics. We conclude that A.
      clavatonanicus produces clavatol and patulin, and that these two polyketides may
      be involved in the protection of T. mairei against attack by plant pathogens by
      this Aspergillus sp.

PMID- 18317752
TI  - Determination of tumour hypoxia with [18F]EF3 in patients with head and neck
      tumours: a phase I study to assess the tracer pharmacokinetics, biodistribution
      and metabolism.
AB  - PURPOSE: The aim of this study was to assess the pharmacokinetics,
      biodistribution and metabolism of [(18)F]EF3, a labelled 2-nitroimidazole hypoxia
      marker, in ten patients with head and neck cancer. METHODS: [(18)F]EF3 was
      administered intravenously (group 1, n=5, mean dose+/-SD: 324+/-108 MBq; group 2,
      n=5, mean dose+/-SD: 1,134+/-138 MBq) to patients (nine male, one female). Blood
      and urine samples and whole-body PET scans were obtained from 20 s to 4-6 h.
      Radioactivity was determined in several regions of interest. RESULTS: No serious
      adverse event was reported. [(18)F]EF3 concentration in blood exhibited a bi
      exponential decline. [(18)F]EF3 was mainly eliminated in the urine. By 7 h 40 min
      after injection, 53+/-14% of the injected dose was collected in the urine. There
      was no significant difference between the low- and high-dose groups. A
      progressive accumulation occurred also in the colon, indicating a hepatobiliary
      excretion. Except in organs involved in the elimination of [(18)F]EF3, the tumour
      to-organ ratio remained close to or below unity in muscle, lungs, heart and brain
      at various times after injection. In one patient, tumour hypoxia was observed
      with a tumour-to-blood ratio ranging from 1.4 to 1.9. Last, [(18)F]EF3 remained
      very stable after injection, with percentage of native tracer above 87% in the
      serum and 84% in the urine. CONCLUSION: Administration of [(18)F]EF3 in head and
      neck cancer patients is feasible and safe. Uptake and retention in tumour was
      observed, indicating the presence of hypoxia.

PMID- 18317753
TI  - Should we use more PET-CT in clinical cardiology?

PMID- 18317754
TI  - HLA typing demands for peptide-based anti-cancer vaccine.
AB  - Immunological treatment of cancer has made some very promising advances during
      the last years. Anti-cancer vaccination using peptides or peptide-pulsed
      dendritic cells and adoptive transfer of in vitro generated, epitope-specific T
      cells depend on a well-fitting interaction of HLA molecule and epitope. Accurate
      HLA-typing is a key factor for successful anti-cancer vaccination. No
      comprehensive data and no suggestion exist on the HLA-typing in this setting. We
      performed a systematic review of PubMed analyzing HLA-typing data in cancer
      vaccination trials over the last 4 years (2004-2007). Then, using the SYFPEITHI
      database, we calculated the peptide binding prediction of the eight most often
      used HLA-A*0201 binding epitopes. Finally, high-resolution typing [by sequence
      specific primers (SSP)] data of a HLA-A*02 or HLA-A*24 positive population in
      Berlin, Germany, were analyzed. Forty-five cancer vaccination trials with 764
      patients were included. Eighteen studies were performed in the USA, 13 in Europe,
      12 in Asia (mainly Japan), and two in Australia. Most common diseases targeted
      were melanoma, prostate cancer, colorectal cancer, renal cell cancer, and breast
      cancer. The trials tested protocols using peptide plus adjuvants without DC or
      protocols using peptide-pulsed DC. In 38 trials (84%) HLA-A2 positive patients
      were vaccinated, in 11 studies (24%) HLA-A24 positive patients were vaccinated.
      Nineteen studies with 291 patients (38%) presented the HLA type as four-digit
      code (high-resolution), 26 studies with 473 patients (62%) presented the HLA-type
      in a low-resolution code. The method of HLA determination was given in six out of
      45 trials (13%). Using the SYFPEITHI database we calculated the peptide binding
      prediction of the eight most often used HLA-A*0201 binding tumor antigen-derived
      epitopes for binding to HLA-A*0203. While the epitopes had a binding score of 17
      28 for HLA-A*0201, the score for binding to HLA-A*0203 was zero in seven out of
      eight tested peptides. Only for one peptide the score was eight. Finally, we
      analyzed high-resolution data of HLA-A*02 and HLA-A*24 positive patients in
      Berlin, Germany. We found the HLA-A*0201 allele and HLA-A*2402 allele in 95%,
      respectively. HLA-A*0201 and HLA-A*2402 are most commonly used for peptide based
      vaccine in cancer. Data on HLA-typing given in the included cancer vaccine
      manuscripts are fractional. Only 13% report the method of HLA typing and most HLA
      types are given as low-resolution code. Looking at the binding of specific
      peptides to both the alleles, it is important to perform high-resolution typing.
      Further suggestions for immunogenetic laboratories and clinical tumor
      immunologists regarding HLA-typing for cancer vaccine trials and adoptive T cell
      transfer approaches are discussed.

PMID- 18317755
TI  - NK cell-mediated targeting of human cancer and possibilities for new means of
      immunotherapy.
AB  - Insights into the molecular basis for natural killer (NK) cell recognition of
      human cancer have been obtained in recent years. Here, we review current
      knowledge on the molecular specificity and function of human NK cells. Evidence
      for NK cell targeting of human tumors is provided and new strategies for NK cell
      based immunotherapy against human cancer are discussed. Based on current
      knowledge, we foresee a development where more cancers may be subject to
      treatment with drugs or other immunomodulatory agents affecting NK cells, either
      directly or indirectly. We also envisage a possibility that certain forms of
      cancers may be subject to treatment with adoptively transferred NK cells, either
      alone or in combination with other therapeutic interventions.

PMID- 18317756
TI  - Minimally invasive percutaneous plate osteosynthesis (MIPPO) technique applied in
      the treatment of humeral shaft distal fractures through a lateral approach.
AB  - The minimally invasive percutaneous plate osteosynthesis (MIPPO) technique
      through the anterior approach has been successfully used in the treatment of
      humeral shaft fractures and has gained satisfactory clinical outcome. An
      anatomical study and a preliminary clinic report were performed to evaluate the
      feasibility of applying the MIPPO technique in the treatment of humeral shaft
      distal fractures through the lateral approach. This study was done on 14 arms
      from seven fresh cadavers. The results of this study showed that it is possible
      to treat humeral shaft distal fractures by using the MIPPO technique through the
      lateral approach. The results of using the MIPPO technique through the lateral
      approach in the treatment of humeral shaft fractures in 22 patients were also
      reviewed.

PMID- 18317757
TI  - Distribution of HFE gene mutations in Slovenian patients with hereditary
      hemochromatosis.

PMID- 18317758
TI  - Soluble transferrin receptor and sTfR-F index for assessing concurrent iron
      deficiency in patients with chronic renal failure.

PMID- 18317759
TI  - Fatal pulmonary and cerebral aspergillosis after a short course of
      corticosteroids for idiopathic thrombocytopenic purpura.

PMID- 18317760
TI  - Response to taxanes in triple negative breast cancer.

PMID- 18317761
TI  - Population pharmacokinetics of aprepitant and dexamethasone in the prevention of
      chemotherapy-induced nausea and vomiting.
AB  - PURPOSE: To develop a population pharmacokinetic model of aprepitant and
      dexamethasone in Japanese patients with cancer, explore the factors that affect
      the pharmacokinetics of aprepitant, and evaluate the effect of aprepitant on the
      clearance of intravenous dexamethasone. METHODS: A total of 897 aprepitant
      concentration measurements were obtained from 290 cancer patients and 25 healthy
      volunteers. For dexamethasone, a total of 847 measurements were obtained from 440
      patients who were co-administered aprepitant (40, 125 mg, or placebo). Plasma
      concentration of aprepitant and dexamethasone were determined by liquid
      chromatography connected with a tandem mass spectrometer and analyzed by a
      population approach using NONMEM software. RESULTS: The plasma concentration time
      course of aprepitant was described using a one-compartment model with first-order
      absorption and lag time. Oral clearance (CL/F) of aprepitant was changed by
      aprepitant dose at doses of 40 or 125 mg. Body weight was the most influential
      intrinsic factor to CL/F of aprepitant. Age, ALT, and BUN also had mild effects
      on the CL/F. Typical population estimates of CL/F, apparent distribution volume
      (V(d)/F), absorption constant (K(a)) and absorption lag time were 1.54 L/h, 72.1
      L, 0.893/h and 0.295 h, respectively. Inter-individual variability in CL/F,
      V(d)/F and K(a) were 53.9, 21.0, and 141%, respectively; intra-individual
      variability was 27.7%. The plasma concentration time course of intravenous
      dexamethasone was also described using a one-compartment model. Clearance of
      dexamethasone was decreased 24.7 and 47.5% by co-administration of aprepitant 40
      and 125 mg. All final model estimates of aprepitant and dexamethasone fell within
      10% of the bootstrapped mean. CONCLUSIONS: A pharmacokinetic model for aprepitant
      has been developed that incorporates body weight, age, ALT, BUN and aprepitant
      dose to predict the CL/F. The results of population pharmacokinetic analysis of
      dexamethasone support dose adjustment of dexamethasone in the case of co
      administration with aprepitant.

PMID- 18317762
TI  - Prevention of cisplatin nephrotoxicity: state of the art and recommendations from
      the European Society of Clinical Pharmacy Special Interest Group on Cancer Care.
AB  - Antineoplastic drugs used in the treatment of cancers present with variable renal
      tolerance profiles. Among drugs with a potential for renal toxicity, platinum
      salts, and especially cisplatin is a well-known agent that may induce acute and
      chronic renal failure. The mechanisms of its renal toxicity and the means of its
      prevention are presented in this article which represent the Clinical
      Recommendation from the Special Interest Group on Cancer Care of the European
      Society of Clinical Pharmacy (ESCP).

PMID- 18317763
TI  - A multicenter phase II study of biweekly paclitaxel and S-1 combination
      chemotherapy for unresectable or recurrent gastric cancer.
AB  - PURPOSE: This Phase II study assessed the activity and safety of biweekly
      paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric
      cancer. The maximum tolerated dose for this regimen had been established
      previously in a Phase I study performed in Japanese patients. PATIENTS AND
      METHODS: Chemotherapy was performed using two anticancer agents, S-1 and
      paclitaxel. Oral S-1 (80 mg/m(2)) was administered twice a day after meals for
      two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period;
      paclitaxel (120 mg/m(2)) was administered intravenously, biweekly, on Days 1 and
      15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles).
      The primary end point was the response rate according to the Response Evaluation
      Criteria in Solid Tumors. RESULTS: A total of 39 patients (median age, 65 years)
      were enrolled; 13 other patients were screened, but found to be ineligible. All
      patients had unresectable and recurrent gastric cancer. The most common treatment
      related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss,
      diarrhea, decreased sodium (each 5%), and anemia, increased alanine
      aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the
      patients experienced alopecia. Intent-to-treat analysis showed a response rate of
      43.6%. With a median follow-up of 14 months (range 8-21 months), median survival
      was 256 days and the median time to progression was 4 months. CONCLUSION: A
      combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and
      showed promising activity against unresectable and recurrent gastric cancer.

PMID- 18317764
TI  - New perspectives on effector mechanisms in uveitis.
AB  - Experimental autoimmune uveitis (EAU) in its several variants represents human
      autoimmune uveitis and has been instrumental in obtaining insights into the basic
      mechanisms of disease. Studies have uncovered that in addition to CD4+ Th1 cells,
      uveitis can be induced also by CD8+ T cells. Antibodies may have a secondary role
      after the blood-retinal barrier has been broken. The role in uveitis of a
      recently discovered IL-17-producing effector T cell type, Th17, is being
      intensively studied. Th17 cells elicit EAU, can be found in uveitic eyes along
      with Th1 cells, and are dominant in some types of EAU. In other types of EAU, Th1
      cells have a dominant role. The dominant effector type is at least in part
      determined by conditions under which initial exposure to self-antigen occurs.
      These findings shed light on the heterogeneity of human disease and may
      ultimately help to develop better and more rational treatment strategies for
      human uveitis.

PMID- 18317765
TI  - Evolution of conditional dispersal: a reaction-diffusion-advection model.
AB  - To study evolution of conditional dispersal, a Lotka-Volterra reaction-diffusion
      advection model for two competing species in a heterogeneous environment is
      proposed and investigated. The two species are assumed to be identical except
      their dispersal strategies: both species disperse by random diffusion and
      advection along environmental gradients, but one species has stronger biased
      movement (i.e., advection along the environmental gradients) than the other one.
      It is shown that at least two scenarios can occur: if only one species has a
      strong tendency to move upward the environmental gradients, the two species can
      coexist since one species mainly pursues resources at places of locally most
      favorable environments while the other relies on resources from other parts of
      the habitat; if both species have such strong biased movements, it can lead to
      overcrowding of the whole population at places of locally most favorable
      environments, which causes the extinction of the species with stronger biased
      movement. These results provide a new mechanism for the coexistence of competing
      species, and they also imply that selection is against excessive advection along
      environmental gradients, and an intermediate biased movement rate may evolve.

PMID- 18317766
TI  - Dynamic hematological disease: a review.
AB  - We review the basic characteristics of four periodic hematological disorders
      (periodic auto-immune hemolytic anemia, cyclical thrombocytopenia, cyclical
      neutropenia and periodic chronic myelogenous leukemia) and examine the role that
      mathematical modeling and numerical simulations have played in our understanding
      of the origin of these diseases and in the regulation of hematopoiesis.

PMID- 18317767
TI  - Transcriptional regulation of Saccharomyces cerevisiae CYS3 encoding
      cystathionine gamma-lyase.
AB  - In studying the regulation of GSH11, the structural gene of the high-affinity
      glutathione transporter (GSH-P1) in Saccharomyces cerevisiae, a cis-acting
      cysteine responsive element, CCGCCACAC (CCG motif), was detected. Like GSH-P1,
      the cystathionine gamma-lyase encoded by CYS3 is induced by sulfur starvation and
      repressed by addition of cysteine to the growth medium. We detected a CCG motif (
      311 to -303) and a CGC motif (CGCCACAC; -193 to -186), which is one base shorter
      than the CCG motif, in the 5'-upstream region of CYS3. One copy of the centromere
      determining element 1, CDE1 (TCACGTGA; -217 to -210), being responsible for
      regulation of the sulfate assimilation pathway genes, was also detected. We
      tested the roles of these three elements in the regulation of CYS3. Using a lacZ
      reporter assay system, we found that the CCG/CGC motif is required for activation
      of CYS3, as well as for its repression by cysteine. In contrast, the CDE1 motif
      was responsible for only activation of CYS3. We also found that two transcription
      factors, Met4 and VDE, are responsible for activation of CYS3 through the CCG/CGC
      and CDE1 motifs. These observations suggest a dual regulation of CYS3 by factors
      that interact with the CDE1 motif and the CCG/CGC motifs.

PMID- 18317768
TI  - Physical activity prevents bone loss in premenopausal women with rheumatoid
      arthritis: a cohort study.
AB  - The aim of the study was to compare the bone loss and the influence of physical
      activity between premenopausal women with rheumatoid arthritis (RA) and healthy
      women. A total of 71 patients with RA and 29 healthy premenopausal women with the
      criteria of the American College of Rheumatology for RA were followed for 2
      years. Of these 85% were Caucasian, aged 38 +/- 6.6 years and with a duration of
      disease of 88 +/- 50 months and 48 (71.8%) used GC, mean daily dose, 7.3 +/- 3.5
      mg. There was a reduction in the T-score of the femoral neck (P = 0.04) and in
      the Ward region (P = 0.05) in RA. Through logistic regression, it was found that
      sedentarism was a risk factor for osteopenia in RA, with relative risk of 1.6 (IC
      = 1.238-1.734). Moderate physical activity reduced the risk of osteopenia by 50%.
      Sedentarism and low weight are the main factors associated with bone loss.
      Physical activity reduces bone loss. Early preventive and therapeutic measures
      must be encouraged.

PMID- 18317769
TI  - Clinical evaluation and comparison of different criteria for classification in
      Turkish patients with psoriatic arthritis.
AB  - Several criteria are being used for the classification of psoriatic arthritis
      (PsA) and there is a lack of consensus about PsA as a separate entity. Our aim is
      to investigate the clinical features of our patients with a clinical diagnosis of
      PsA, compare the sensitivities of different classification criteria and agreement
      between the criteria. In this study 86 PsA patients were investigated (48 female,
      mean age 44). Moll and Wright criteria were fulfilled by 91%, Vasey and Espinoza
      criteria by 94% and modified European SpA study group criteria by 59%,
      classification of PsA study group criteria by 86%, modified McGonagle criteria by
      96%, Fournie et al. criteria by 84%, and Gladman criteria by 95%. Significant
      agreement was present between criteria but generally kappa values were less than
      0.5. The pattern of PsA can differ with time and the implementation of the
      available classification criteria showed considerable differences.

PMID- 18317770
TI  - A comparative evaluation of health related quality of life and depression in
      patients with fibromyalgia syndrome and rheumatoid arthritis.
AB  - The aim of this study was to compare health related quality of life (HRQoL) and
      assess functional and psychological status in rheumatoid arthritis (RA),
      fibromyalgia syndrome (FS) patients and controls (each 30 subjects). Demographic
      characteristics, pain and sleep disturbance by Visual Analog Scale, depression by
      Beck Depression Inventory (BDI), disease impact by fibromyalgia impact
      questionnaire, DAS-28, and HRQoL by SF-36 were gathered. The FS group scored
      significantly worser than the RA group with respect to physical role, social
      functioning and bodily pain subscales of SF-36. The scores of all SF-36 subscales
      were significantly lower in FS and RA patients than controls except mental health
      score. All of the subscales of SF-36 were negatively correlated with BDI scores
      in FS patients. In RA group, the DAS-28 scores were inversely correlated with all
      of SF-36 subscales. In conclusion, presence of comorbid depression must be taken
      into account when determining HRQoL in FS and RA. Essentials improving the HRQoL
      are management of depression in FS and control of disease activity in RA.

PMID- 18317771
TI  - Molecular aspects of osteopathy in type 1 Gaucher disease: correlation between
      genetics and bone density.
AB  - Bone-related complications in Gaucher disease are considered to be poorly
      responsive to specific enzyme replacement therapy. Polymorphisms of candidate
      genes associated with low bone density were investigated to see whether they are
      correlated with bone mineral density (BMD) and bone involvement in Gaucher
      disease. Genotyping for polymorphisms in candidate genes (interleukins 1alpha and
      1beta, interleukin-1 receptor antagonist; cytochrome P450; collagen 1A1; low
      density Lipoprotein Receptor; bone morphogenic protein 4; vitamin D receptor; and
      estrogen receptor 2beta) were performed using standard methodologies. BMD was
      measured by dual energy X-ray absorptiometry (DXA). One hundred and ninety-four
      patients and 100 controls were genotyped for the above polymorphisms. Thirteen
      haplotypes were obtained, with several correlations with BMD in patients; also, a
      haplotype (T889-T3954-C511-240VNTR of IL1) was significantly correlated with T
      scores and Z-score for femur neck and lumbar spine (p = 0.01) in patients.
      Haplotypes of bone-specific candidate genes associated with BMD may predict
      severity of these features in Gaucher disease.

PMID- 18317772
TI  - Genetic control of somatic embryogenesis induction in Eucalyptus globulus Labill.
AB  - A reproducible protocol for somatic embryogenesis (SE) induction in Eucalyptus
      globulus from mature zygotic embryos is available since 2002. However, for the
      use of SE in tree breeding programs, the frequency of SE initiation needs to be
      improved and controlled, and this was investigated in 13 open-pollinated (OP)
      families over three consecutive years. A diallel mating design with five parent
      trees was used to study genetic control of SE induction. Results showed that SE
      induction varies across E. globulus families and over the years of seed
      production tested. Somatic embryogenesis was initiated on explants from 84% of
      the OP families tested in 2002 and 100% of the families tested in 2003 and 2004.
      The year 2003 gave best results for percentage of induction and total number of
      somatic embryos produced. Results concerning genetic control showed that SE
      induction is under the control of additive genetic effects, as 22.0% of variation
      in SE initiation was due to general combining ability (GCA) effect, whereas 6.4%
      was due to maternal effects. Neither specific combining ability (SCA) nor
      reciprocal effects were significant.

PMID- 18317773
TI  - Development of a transient expression system in grapevine via agro-infiltration.
AB  - Transient expression of genes using Agrobacterium is a powerful tool for the
      analysis of gene function in plants. We have developed this method for the
      analysis of genes involved in disease resistance in grapevine leaves. Our
      research showed that the quality of the plant material, the plant genotype used
      for agro-infiltration and the presence of additional virulence factors (carried
      on plasmid pCH32) in the Agrobacterium strain are all important factors for
      success of the procedure. After optimising these factors, we consistently achieve
      sufficient acceptable levels of expression of the markers beta-glucuronidase
      (GUS) and green fluorescent protein (GFP) using vacuum infiltration of grapevine
      leaves from plants grown in vitro. We used this procedure to investigate the
      proposed role of stilbenes in defense against grapevine downy mildew (Plasmopara
      viticola) by transiently overexpressing stilbene synthase in grapevine leaves,
      before infection with P. viticola. We found that agro-infiltration itself induces
      the synthesis of stilbenes in grapevine leaves, thus preventing us to test the
      effect of the overexpression of stilbene synthase in defense. However, our
      results revealed that agro-infiltration before P. viticola inoculation had an
      effect on the development of the infection. Further research is required to show
      whether stilbenes or some other factor are the causal agent restricting pathogen
      development. The method described here provides and excellent tool to exploit at
      the many grapevine genomic resources now available, and will contribute to a
      better understanding of many areas of grapevine biology.

PMID- 18317774
TI  - Construction of the physical map of the gpa7 locus reveals that a large segment
      was deleted during rice domestication.
AB  - To facilitate cloning gene(s) underlying gpa7, a deep-coverage BAC library was
      constructed for an isolate of common wild rice (Oryza rufipogon Griff.) collected
      from Dongxiang, Jiangxi Province, China (DXCWR). gpa7, a quantitative trait locus
      corresponding to grain number per panicle, is positioned in the short arm of
      chromosome 7. The BAC library containing 96,768 clones represents approximate 18
      haploid genome equivalents. The contig spanning DXCWR gpa7 was constructed with a
      series of ordered markers. The putative physical map near the gpa7 locus of
      another accession of O. rufipogon (Accession: IRGC 105491) was also isolated in
      silico. Analysis of the physical maps of gpa7 indicated that a segment of about
      150 kb was deleted during domestication of common wild rice.

PMID- 18317775
TI  - Evaluation of selection strategies alternative to nptII in genetic transformation
      of citrus.
AB  - The neomycin phosphotransferase (nptII) selection system has proved successful in
      citrus transformation; however, it may be recommendable to replace it given the
      pressure exerted against antibiotic-resistance selectable marker genes in
      transgenic plants. The present work investigates three different selection
      alternatives, comparing them to nptII selection in two citrus genotypes, Carrizo
      citrange and Pineapple sweet orange. The first method used the beta-glucuronidase
      (uidA) reporter marker gene for selection; the second attempted to generate
      marker-free plants by transforming explants with a multi-auto-transformation
      (MAT) vector, combining an inducible R/RS-specific recombination system with
      transgenic-shoot selection through expression of isopentenyl transferase (ipt)
      and indoleacetamide hydrolase/tryptophan monooxygenase (iaaM/H) marker genes;
      while the third exploited the phosphomannose isomerase (PMI)/mannose conditional
      positive selection system. Firstly, GUS screening of all regenerated shoots in
      kanamycin-free medium gave 4.3% transformation efficiency for both genotypes.
      Secondly, workable transformation efficiencies were also achieved with the MAT
      system, 7.2% for citrange and 6.7% for sweet orange. This system affords an
      additional advantage as it enables selectable marker genes to be used during the
      in vitro culture phase and later removed from the transgenic plants by inducible
      recombination and site-specific excision. Thirdly, the highest transformation
      rates were obtained with the PMI/mannose system, 30% for citrange and 13% for
      sweet orange, which indicates that this marker is also an excellent candidate for
      citrus transformation.

PMID- 18317776
TI  - Creation and analysis of a novel chimeric promoter for the complete containment
      of pollen- and seed-mediated gene flow.
AB  - Effective containment of gene flow in transgenic plants requires a promoter that
      is highly specific for male and female gametes or tissues. Here, we report the
      creation of a novel pollen-, stigma- and carpel-specific (PSC) promoter through
      the fusion of the pollen-specific LAT52 and carpel-specific AGL5 enhancers to a
      stigma-specific SLG promoter. Gene expression analysis showed that fusion of the
      LAT52 enhancer to the SLG promoter enables the latter to gain pollen-specific
      activity while the acquirement of carpel-specific activity requires the correct
      orientation of the inserted AGL5 enhancer in the PSC promoter, and only a forward
      but not a reverse-oriented one is functional. The resulting fPSC promoter, when
      fused to DT-A, generated at least three aberrant gynoecium phenotypes. Type I
      plants exhibited shortened stigmatic tissues, resembling plants containing the DT
      A gene controlled by the SLG promoter. However, type II and III plants displayed
      partial or complete ablation of gynoecia, and were unable to support the
      reproductive process. Type II and III plants also produced severely perturbed
      anthers and pollen in comparison to type I or SLG::DT-A plants, and transgenic
      pollen grains were unable, when out-crossed with control plants, to pass the
      transgene to the next generation in all plants examined, indicating that they are
      selectively eliminated. This tissue-specific ablation or perturbation is highly
      specific, and does not compromise vegetative growth. Evidently, the fPSC promoter
      faithfully acquires tissue specificity from the incorporated enhancers and
      promoter, and should have a practical application for transgene containment in
      non-fruit and -grain producing plant crops.

PMID- 18317777
TI  - Arabidopsis R2R3-MYB transcription factor AtMYB60 functions as a transcriptional
      repressor of anthocyanin biosynthesis in lettuce (Lactuca sativa).
AB  - The MYB transcription factors play important roles in the regulation of many
      secondary metabolites at the transcriptional level. We evaluated the possible
      roles of the Arabidopsis R2R3-MYB transcription factors in flavonoid biosynthesis
      because they are induced by UV-B irradiation but their associated phenotypes are
      largely unexplored. We isolated their genes by RACE-PCR, and performed transgenic
      approach and metabolite analyses in lettuce (Lactuca sativa). We found that one
      member of this protein family, AtMYB60, inhibits anthocyanin biosynthesis in the
      lettuce plant. Wild-type lettuce normally accumulates anthocyanin, predominantly
      cyanidin and traces of delphinidin, and develops a red pigmentation. However, the
      production and accumulation of anthocyanin pigments in AtMYB60-overexpressing
      lettuce was inhibited. Using RT-PCR analysis, we also identified the complete
      absence or reduction of dihydroflavonol 4-reductase (DFR) transcripts in AtMYB60-
      overexpressing lettuce (AtMYB60-117 and AtMYB60-112 lines). The correlation
      between the overexpression of AtMYB60 and the inhibition of anthocyanin
      accumulation suggests that the transcription factorAtMYB60 controls anthocyanin
      biosynthesis in the lettuce leaf. Clarification of the roles of the AtMYB60
      transcription factor will facilitate further studies and provide genetic tools to
      better understand the regulation in plants of the genes controlled by the MYB
      type transcription factors. Furthermore, the characterization of AtMYB60 has
      implications for the development of new varieties of lettuce and other
      commercially important plants with metabolic engineering approaches.

PMID- 18317778
TI  - [Arteriovenous dissection for branch retinal vein occlusion].
AB  - Arteriovenous dissection (AVD) is a surgical maneuver to separate the retinal
      artery and vein at the crossing site in patients with branch retinal vein
      occlusion (BRVO). The published studies showed an evidence level 3. AVD seems to
      be maintainable in patients with recent onset of BRVO and decimal visual acuity <
      or =0.4.

PMID- 18317779
TI  - Complications of endoscopic third ventriculostomy.
AB  - OBJECTS: Although endoscopic third ventriculostomy (ETV) is considered as the
      first choice in the management of noncommunicating hydrocephalus, it is not
      without risk or complication. METHODS: The patients who had undergone ETV only
      between 1998 and 2005 were retrospectively reviewed. There were 85 males and 70
      females, and 173 ETVs were performed in 155 patients. The patients' age ranged
      from 2 months to 77 years. Complications were categorized as (1) intraoperative,
      (2) early postoperative (<1 month), and (3) late postoperative (>1 month). Follow
      up of the patients ranged from 1 to 86 months. RESULTS: Overall complication rate
      per patient was 15.4%, and complication per procedure was 18%. Complication rate
      significantly varied with the etiology of hydrocephalus (P = 0.013). The patients
      with Chiari type I malformation and tumor had no or very low complication rates.
      The complication risk was significantly higher in repeat endoscopic procedure
      (55.5%) than in the first procedure (10%; P = 0.0001). CONCLUSION: ETV should be
      the first choice in the management of noncommunicating hydrocephalus. Training,
      experience, and meticulous technique will decrease the complication rate.
      Patients undergoing ETV should be followed in a similar manner to patients with
      cerebrospinal fluid shunts.

PMID- 18317780
TI  - Microsurgical removal of intramedullary spinal cord gliomas in a rat spinal cord
      decreases onset to paresis, an animal model for intramedullary tumor treatment.
AB  - OBJECTIVE: Intramedullary spinal cord tumors (IMSCT) pose significant challenges
      given their recurrence rate and limited treatment options. Using our previously
      described rat model of IMSCT, we describe a technique for microsurgical tumor
      resection and present the functional and histopathological analysis of tumor
      progression. METHODS: Twenty-four Fischer 344 rats were randomized into two
      groups. All animals received a 5-microl intramedullary injection of 9L
      gliosarcoma cells. Animals were evaluated daily for signs of paralysis using the
      Basso, Beattie, and Bresnahan (BBB) scale. Group 1 continued with daily
      assessments using the BBB scale following tumor implantation, but received no
      further treatment. Group 2 underwent surgical removal of intramedullary tumor on
      postoperative day five. At a BBB score less than 5 (e.g., functional paraplegia),
      all animals of both groups were killed and sent for histopathological analysis.
      RESULTS: Group 1 had a median onset of functional hind limb paraplegia at 15 +/-
      1.0 days. Group 2 had a median onset of hind limb paresis at 53 +/- 0.46 days.
      Hematoxylin-eosin cross-sections confirmed the presence of intramedullary 9L
      tumor invading the spinal cord in both groups. CONCLUSION: Animals with 9L IMSCTs
      consistently developed hind limb paraplegia in a reliable and reproducible
      manner. Animals undergoing microsurgical resection of IMSCT had a significant
      delay in the onset of functional paraplegia compared to the untreated controls.
      These findings suggest that this model may mimic the behavior of IMSCTs following
      operative resection in humans and thus may be used to examine efficacy of new
      treatment options for high-grade intramedullary tumors.

PMID- 18317781
TI  - Haemangiomas and vascular malformations of the limb in children: the role of
      pressure garments.

PMID- 18317782
TI  - Cellular distribution of vascular endothelial growth factor A (VEGFA) and B
      (VEGFB) and VEGF receptors 1 and 2 in focal cortical dysplasia type IIB.
AB  - Members of the vascular endothelial growth factor (VEGF) family are key signaling
      proteins in the induction and regulation of angiogenesis, both during development
      and in pathological conditions. However, signaling mediated through VEGF family
      proteins and their receptors has recently been shown to have direct effects on
      neurons and glial cells. In the present study, we immunocytochemically
      investigated the expression and cellular distribution of VEGFA, VEGFB, and their
      associated receptors (VEGFR-1 and VEGFR-2) in focal cortical dysplasia (FCD) type
      IIB from patients with medically intractable epilepsy. Histologically normal
      temporal cortex and perilesional regions displayed neuronal immunoreactivity (IR)
      for VEGFA, VEGFB, and VEGF receptors (VEGFR-1 and VEGFR-2), mainly in pyramidal
      neurons. Weak IR was observed in blood vessels and there was no notable glial IR
      within the grey and white matter. In all FCD specimens, VEGFA, VEGFB, and both
      VEGF receptors were highly expressed in dysplastic neurons. IR in astroglial and
      balloon cells was observed for VEGFA and its receptors. VEGFR-1 displayed strong
      endothelial staining in FCD. Double-labeling also showed expression of VEGFA,
      VEGFB and VEGFR-1 in cells of the microglia/macrophage lineage. The neuronal
      expression of both VEGFA and VEGFB, together with their specific receptors in
      FCD, suggests autocrine/paracrine effects on dysplastic neurons. These
      autocrine/paracrine effects could play a role in the development of FCD,
      preventing the death of abnormal neuronal cells. In addition, the expression of
      VEGFA and its receptors in glial cells within the dysplastic cortex indicates
      that VEGF-mediated signaling could contribute to astroglial activation and
      associated inflammatory reactions.

PMID- 18317783
TI  - Prenatal exposure to passive smoking and duration of breastfeeding in nonsmoking
      women: Krakow inner city prospective cohort study.
AB  - INTRODUCTION: The relationship between tobacco smoking in pregnancy and
      breastfeeding is of public health importance. The present birth cohort study
      provided the opportunity to investigate whether the negative relationship between
      passive smoking measured by the cotinine concentrations in maternal blood at
      delivery and breastfeeding in postpartum could also be confirmed in nonsmoking
      mothers. MATERIALS AND METHODS: The study sample included 441 healthy pregnant
      women who were recruited in the first and second trimester of pregnancy.
      Enrollment included only nonsmoking women of the age of 18-35 years with
      singleton pregnancies, without illicit drug use and free from chronic diseases.
      After delivery, breastfeeding duration was defined using the answers recorded in
      the interviews with mothers conducted every 3 months. An infant was considered to
      be fully breastfed when breast milk was the only source of nourishment. Any
      breastfeeding was defined as an infant's being fully breastfed or receiving both
      breast milk and formula, with or without solids. In the statistical analysis only
      total duration of breastfeeding up to 6 months was considered for both forms of
      breastfeeding. Subjects were categorized into environmental tobacco smoke (ETS)
      exposure groups according to maternal blood cotinine level at delivery or self
      reported exposure to ETS during pregnancy. RESULTS: The adjusted relative risk of
      discontinuation of any breastfeeding after infant's first 6 months was more than
      two times higher (OR = 2.42; 95% CI: 1.42-4.14) in women whose blood cotinine
      level at delivery was above 75th percentile of cotinine distribution (>0.15
      ng/mL); the corresponding risk of discontinuation of full breastfeeding was OR =
      1.71; 95% CI: 1.03-2.82. Estimated relative risk of discontinuation of any
      breastfeeding based on self-reported ETS was also significant but much less
      marked; the corresponding risk of discontinuation of full breastfeeding was
      insignificant. CONCLUSION: The results obtained support the hypothesis that ETS
      may affect breastfeeding duration and support the avoidance of passive smoking as
      a necessary additional measure for breastfeeding promotion.

PMID- 18317784
TI  - Vaginal wall fibroid.
AB  - Localization of leiomyomas in the vaginal wall is very rare. We report about a
      case of a vaginal leiomyoma in the anterior vaginal wall, preoperatively
      identified with sonography and CT. Surgical enucleation was performed. Surgical
      removal in these cases is safe and usually with minimal bleeding.

PMID- 18317785
TI  - Adaptation process of the skin graft to vaginal mucosa after McIndoe
      vaginoplasty.
AB  - OBJECTIVE: There are many methods of treatment of vaginal agenesis. METHODS: In
      this study, patients who underwent McIndoe vaginoplasty were evaluated for
      development of vaginal mucosa. Vaginal pH measurements, smears, and punch
      biopsies were obtained from seven patients postoperatively at 3, 6, and 12 months
      after having McIndoe vaginoplasty. RESULTS: Neovaginal smears indicated no
      specific data for mucosal development at the 3rd and 6th month after the
      operation. However, Doderlein bacilli were determined at the 12th month.
      Histopathological examination of punch biopsies revealed dermal and subdermal
      thickening at the 3rd month, partial adaptation to mucosa at 6th month, and full
      adaptation to mucosa at 12th month. Also normal vaginal pH levels were recorded
      at the 12th month. CONCLUSION: As a result of the adaptation process, the split
      thickness skin graft acquired both histological and physiological characteristics
      of normal vaginal mucosa. Also, neovaginal epithelium was evaluated to be
      macroscopically similar to normal vaginal mucosa, 12 months after the operation.

PMID- 18317786
TI  - Detection of hormone receptors in the human vocal fold.
AB  - Until now only limited and controversial data are available concerning the
      presence of steroid hormone receptors in the human vocal fold. A sum of 140
      slides from 104 patients were investigated including 25 Reinke's edemas, 19 cases
      of recurrent respiratory papillomatosis, 19 polyps, 10 epithelial hyperplasias
      without or with dysplasias, 4 carcinomas in situ, 20 laryngeal carcinomas as well
      as 7 fresh cadaver samples without macroscopic alterations. The median patient
      age was 58 years. Paraffin-embedded tissue was incubated with monoclonal
      antibodies for estrogen-alpha, androgen and progesterone. Androgen receptors were
      expressed most frequently, followed by estrogen receptors, whereas no
      progesterone receptors were identified. Receptor staining could be detected with
      different densities and locations within the different vocal fold pathologies,
      but not in the autopsy samples. Our study could clearly demonstrate the presence
      of hormone receptors in the human vocal fold. Androgen receptors were most
      frequently detected, especially in the basal and intermediate layer of the
      stratified epithelium and the lamina propria. Whether the high incidence of
      steroid hormone receptors in some vocal fold pathologies has implications on
      their pathogenesis must be evaluated by further studies.

PMID- 18317787
TI  - Tinnitus with or without hearing loss: are its characteristics different?
AB  - The present study was carried out in order to analyze the clinical
      characteristics of tinnitus both in normal hearing subjects and in patients with
      hearing loss. The study considered 520 consecutive tinnitus sufferers. The
      following parameters were considered: age, sex, subjective disturbance caused by
      tinnitus, subjective judgment of tinnitus intensity, tinnitus laterality,
      tinnitus duration, tinnitus measurements, normal hearing or associated hearing
      loss. Among the patients considered, 223 have normal hearing while 297 have a
      hearing deficit. The hearing impairment was found to be in most cases of
      sensorineural type. The subjective discomfort is higher in presence of hearing
      loss. Subjects with hearing loss needed significantly higher masking levels. No
      evident differences in the residual inhibition (RI) result between the two groups
      were found. The present study confirms that tinnitus is most frequently
      associated with hearing loss. The characteristics of tinnitus in normal hearing
      subjects, except for the subjective judgment of tinnitus intensity, the pitch and
      the RI, are significantly different for those observed in subjects with hearing
      loss. The association of tinnitus and hearing deficit seems to increase the
      perceived severity of the symptom.

PMID- 18317788
TI  - Novel treatment of atrophic rhinitis: early results.
AB  - The aim of this randomized control trial, performed at a tertiary referral
      hospital, was to compare the therapeutic effectiveness of two novel treatment
      modalities, oral rifampicin and submucosal placentrex injection, in randomly
      selected patients of primary atrophic rhinitis regarding objective, subjective
      and histopathological improvement. Patients treated with oral rifampicin showed
      most promising results regarding objective, subjective and histopathological
      improvement with maximum disease-free interval on regular follow-up as compared
      to submucosal placentrex injections.

PMID- 18317789
TI  - Potassium titanyl phosphate laser treatment of intubation vocal granuloma.
AB  - Vocal process granuloma is an uncommon occurrence which is possibly related to
      endotrachial intubation. Despite its infrequent occurrence, intubation vocal
      granuloma has received considerable attention in the literature on account of its
      versatile clinical managements and various results. We presented a series of
      cases afflicted with intubation vocal granuloma and documented the promising
      effect of potassium titanyl phosphate (KTP) laser ablation. Twelve patients of
      intubation vocal granuloma had been retrospectively reviewed at Tri-Service
      General Hospital from January 1999 to June 2006. Detailed history taking,
      physical examination, and voice analysis were conducted in all patients before
      and after this surgical intervention. They all underwent KTP laser ablation of
      vocal granuloma. Patients were 7 females and 5 males with a mean age of 46.8
      years. The grade of hoarseness, roughness, breathiness, asthenia, and strain
      (GRBAS) scale and maximum phonation time (MPT) showed significant different
      before and after this surgical intervention (P < 0.05). There was no recurrence
      in all patients for at least 14 months in the follow-up. We have found that KTP
      laser microlaryngosurgery can be a useful therapy and can lead avoidance of
      repetitive surgical procedures.

PMID- 18317790
TI  - Cytokine changes after surgical treatment of obstructive sleep apnoea syndrome.
AB  - Obstructive sleep apnoea syndrome (OSAS) is associated with inflammatory
      processes and elevated plasma cytokines. This study assesses the effect of
      surgery in cytokine levels of OSAS patients. A total of 24 male patients with
      mild to moderate OSAS, confirmed with polysomnography underwent septoplasty and
      uvulo-palato-pharyngoplasty in a period of a year. Control group consisted of 12
      overweighted subjects and 15 obese subjects. Peripheral venous blood was
      collected from each patient 1 week before surgical treatment and 6 months
      postoperatively. Spontaneous production of tumour necrosis factor (TNF-a) by
      monocytes and serum levels of IL-1beta and IL-6 were investigated. Control
      subjects were also examined for the same pro-inflammatory cytokines. Production
      of TNF-a and IL-6 were significantly elevated in OSAS patients and obese controls
      compared with overweighted control subjects (p < 0.05). Serum levels of IL-1beta
      did not differ among the study groups. Preoperative cytokine values were
      significantly correlated with the preoperative body mass index (BMI) and the
      apnoea/hypopnoea index (AHI) in OSAS patients. Surgery resulted a significant
      reduction in the TNF-a and IL-6 values of the study group. Decrease in cytokine
      level was strongly correlated with the AHI decrease. The postoperative relative
      percentage change of IL-6 values was significantly higher than this of TNF-a (p <
      0.001). Surgical management of mild to moderate OSAS leads to a significant
      reduction in TNF-a and IL-6 values. Our data indicate that AHI is an independent
      risk factor of systemic inflammation; however it affects cytokines to a lesser
      degree compared with the BMI.

PMID- 18317791
TI  - HIV-associated cerebral lymphocyte infiltration mimicking vestibular schwannoma.
AB  - The association of unilateral, rapidly progressive hearing loss, tinnitus and
      vestibular dysfunction in combination with a contrast-enhancing mass within the
      internal auditory canal on MRI is suggestive of a vestibular schwannoma (VS). We
      report the rare finding of a HIV-associated cerebral lymphocyte infiltration,
      most probably malignant lymphoma, which was presumed initially to be a VS. A 36
      year-old male presented with progressive unilateral hearing loss accompanied by
      acute, ipsilateral tinnitus. Interpreted first as sudden sensorineural hearing
      loss, his symptoms were treated with rheologic therapy. Ipsilateral facial palsy
      appeared. MRI with gadolininium disclosed a contrast-enhancing mass within the
      internal auditory meatus of the left side. Within five weeks an extended
      leptomeningeal lymphocyte infiltration evolved and the diagnosis of an underlying
      HIV infection was made. Unilateral, rapidly progressive hearing loss and a fast
      growing cerebello-pontine mass is atypical for VS and highly suspicious of
      malignant disease. To our knowledge we report the first case of an HIV-associated
      cerebral lymphocyte infiltration, mimicking a VS. In such cases the diagnostic
      work-up should include a HIV test.

PMID- 18317792
TI  - Defining the role of Emi1 in the DNA replication-segregation cycle.
AB  - Ordered progression through the cell cycle is essential to maintain genomic
      stability, and fundamental to this is ubiquitin-mediated proteolysis. In
      particular, the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase
      destabilises specific regulators at defined times in the cycle to ensure that
      each round of DNA replication is followed by cell division. Thus, the proper
      regulation of the APC/C is crucial in each cell cycle. There are several APC/C
      regulators that restrict its activity to specific cell cycle phases, and amongst
      these the early mitotic inhibitor 1 (Emi1) protein has recently come to
      prominence. Emi1 has been proposed to control APC/C in early mitosis; however,
      recent evidence questions this role. In this review we discuss new evidence that
      indicates that Emi1 is essential to restrict APC/C activity in interphase and, by
      doing so, ensure the proper coordination between DNA replication and mitosis.

PMID- 18317793
TI  - Integrated cytogenetic map of mitotic metaphase chromosome 9 of maize:
      resolution, sensitivity, and banding paint development.
AB  - To study the correlation of the sequence positions on the physical DNA finger
      print contig (FPC) map and cytogenetic maps of pachytene and somatic maize
      chromosomes, sequences located along the chromosome 9 FPC map approximately every
      10 Mb were selected to place on maize chromosomes using fluorescent in situ
      hybridization (FISH). The probes were produced as pooled polymerase chain
      reaction products based on sequences of genetic markers or repeat-free portions
      of mapped bacterial artificial chromosome (BAC) clones. Fifteen probes were
      visualized on chromosome 9. The cytological positions of most sequences
      correspond on the pachytene, somatic, and FPC maps except some probes at the
      pericentromeric regions. Because of unequal condensation of mitotic metaphase
      chromosomes, being lower at pericentromeric regions and higher in the arms, probe
      positions are displaced to the distal ends of both arms. The axial resolution of
      FISH on somatic chromosome 9 varied from 3.3 to 8.2 Mb, which is 12-30 times
      lower than on pachytene chromosomes. The probe collection can be used as
      chromosomal landmarks or as a "banding paint" for the physical mapping of
      sequences including transgenes and BAC clones and for studying chromosomal
      rearrangements.

PMID- 18317794
TI  - Globally consistent depth sorting of overlapping 2D surfaces in a model using
      local recurrent interactions.
AB  - The human visual system utilizes depth information as a major cue to group
      together visual items constituting an object and to segregate them from items
      belonging to other objects in the visual scene. Depth information can be inferred
      from a variety of different visual cues, such as disparity, occlusions and
      perspective. Many of these cues provide only local and relative information about
      the depth of objects. For example, at occlusions, T-junctions indicate the local
      relative depth precedence of surface patches. However, in order to obtain a
      globally consistent interpretation of the depth relations between the surfaces
      and objects in a visual scene, a mechanism is necessary that globally propagates
      such local and relative information. We present a computational framework in
      which depth information derived from T-junctions is propagated along surface
      contours using local recurrent interactions between neighboring neurons. We
      demonstrate that within this framework a globally consistent depth sorting of
      overlapping surfaces can be obtained on the basis of local interactions. Unlike
      previous approaches in which locally restricted cell interactions could merely
      distinguish between two depths (figure and ground), our model can also represent
      several intermediate depth positions. Our approach is an extension of a previous
      model of recurrent V1-V2 interaction for contour processing and illusory contour
      formation. Based on the contour representation created by this model, a recursive
      scheme of local interactions subsequently achieves a globally consistent depth
      sorting of several overlapping surfaces. Within this framework, the induction of
      illusory contours by the model of recurrent V1-V2 interaction gives rise to the
      figure-ground segmentation of illusory figures such as a Kanizsa square.

PMID- 18317795
TI  - Surgery and adjuvant therapies in the treatment of stage IV melanoma: our
      experience in 84 patients.
AB  - BACKGROUND AND AIMS: Survival rates of patients with stage IV melanoma are poor:
      Median survival is 7-8 months and 5-year survival rates about 5%. There is no
      agreement on the role of surgery at this stage. Most patients with metastatic
      melanoma are not able to undergo resection and usually are sent to systemic chemo
      and immunotherapy. PATIENTS AND METHODS: Eighty-four patients operated on for
      stage IV melanoma were evaluated. Of them, 61.9% were submitted to reiterative
      surgery with 168 operations and 182 surgical procedures overall. A total of 90.5%
      was submitted to adjuvant therapies according to aggressive and reiterated
      schedules: chemotherapy, immunotherapy, dendritic cells vaccine, infusion of
      tumor infiltrating lymphocytes, local therapies as electrochemotherapy. RESULTS:
      The mean overall survival (Kaplan-Meier) was 56.7 months (1 year: 72.1%, 3 years:
      46.5%, 5 years: 23.16%). The survival of reiterative surgery was significatively
      longer than single surgery (62.7 vs 42.4 months, median 50.9 vs 16.0), p = 0.03.
      Multivariated Cox analysis was performed for disease-free interval, repeated
      surgery, adjuvant therapies, and site of metastasis according to the American
      Joint Committee on Cancer: Reiterative surgery was shown as an independent
      prognostic factor (p < 0.05). CONCLUSION: Metastatic resection associated with
      adjuvant therapy may improve overall survival and, in some instances, can provide
      long-term survival, whatever site and numbers of metastasis. In our series,
      reiterative surgery was more significatively efficient in improving survival than
      single-time surgery.

PMID- 18317796
TI  - OsCYT-INV1 for alkaline/neutral invertase is involved in root cell development
      and reproductivity in rice (Oryza sativa L.).
AB  - A short root mutant was isolated from an EMS-generated rice mutant library. Under
      normal growth conditions, the mutant exhibited short root, delayed flowering, and
      partial sterility. Some sections of the roots revealed that the cell length along
      the longitudinal axis was reduced and the cell shape in the root elongation zone
      shrank. Genetic analysis indicated that the short root phenotype was controlled
      by a recessive gene. Map-based cloning revealed that a nucleotide substitution
      causing an amino acid change from Gly to Arg occurred in the predicted rice gene
      (Os02g0550600). It coded an alkaline/neutral invertase and was homologous to
      Arabidopsis gene AtCyt-inv1. This gene was designated as OsCyt-inv1. The results
      of carbohydrate analysis showed an accumulation of sucrose and reduction of
      hexose in the Oscyt-inv1 mutant. Exogenously supplying glucose could rescue the
      root growth defects of the Oscyt-inv1 mutant. These results indicated that OsCyt
      inv1 played important roles in root cell development and reproductivity in rice.

PMID- 18317797
TI  - NADPH oxidase involvement in cellular integrity.
AB  - NADPH oxidase activity is involved in plant adaptation and development. The
      reactive oxygen species sourced by NADPH oxidase activity may contribute to wall
      strength and protoplast volume adjustment. Root hair bulge apices of the NADPH
      oxidase mutant rhd2/Atrbohc were more robust than the kjk cellulose synthase
      mutant, but burst more readily than the wild type (WT). Root epidermal wall
      appeared impaired in rhd2/Atrbohc, as revealed by the number of protoplasts
      released by wall-degrading enzymes. Root hair bulges of rhd2/Atrbohc burst more
      than the WT when challenged in situ with hypo-osmotic low ionic strength medium.
      Inhibition of NADPH oxidase activity with diphenylene iodonium caused WT to
      phenocopy the rhd2/Atrbohc bursting in response to hypo-osmotic shock. This
      implicates RHD2/AtRBOHC in softening the cell wall to permit protoplast
      expansion. Overall, the results point to a role for RHD2/AtRBOHC in contributing
      to wall strength.

PMID- 18317798
TI  - Two different effects of calcium on aquaporins in salinity-stressed pepper
      plants.
AB  - Two different effects of calcium were studied, respectively, in plasma membrane
      vesicles and in protoplasts isolated from roots of control pepper plants
      (Capsicum annuum L cv. California) or of plants treated with 50 mM NaCl, 10 mM
      CaCl(2) or 10 mM CaCl(2) + 50 mM NaCl. Under saline conditions, osmotic water
      permeability (P ( f )) values decreased in protoplasts and plasma membrane
      vesicles, and the same reduction was observed in the PIP1 aquaporin abundance,
      indicating inhibitory effects of NaCl on aquaporin functionality and protein
      abundance. The cytosolic Ca(2+) concentration, [Ca(2+)](cyt), was reduced by
      salinity, as observed by confocal microscope analysis. Two different actions of
      Ca(2+) were observed. On the one hand, increase in free cytosolic calcium
      concentrations associated with stress perception may lead to aquaporin closure.
      On the other hand, when critical requirements of Ca(2+) were reduced (by
      salinity), and extra-calcium would lead to an upregulation of aquaporins,
      indicating that a positive role of calcium at whole plant level combined with an
      inhibitory mechanism at aquaporin level may work in the regulation of pepper root
      water transport under salt stress. However, a link between these observations and
      other cell signalling in relation to water channel gating remains to be
      established.

PMID- 18317799
TI  - Fruit ripening in Vitis vinifera: apoplastic solute accumulation accounts for pre
      veraison turgor loss in berries.
AB  - In Vitis vinifera L. berries, the onset of ripening (known as "veraison")
      involves loss of turgor (P) in the mesocarp cells. We hypothesized that P loss
      was associated with an accumulation of apoplastic solutes in mesocarp tissue
      prior to veraison. Apoplastic sap was extracted from the mesocarp by
      centrifugation at the appropriate gravity to measure the apoplast solute
      potential (Psi (s) (A) ) and assay the sap composition. The Psi (s) (A) was about
      -0.2 MPa early in development, decreased about 1.0 MPa by veraison, and continued
      to decrease during ripening to almost -4.0 MPa by the end of berry development.
      Potassium, malate, tartrate, proline, glucose, fructose, and sucrose were
      quantified in apoplastic sap. The calculated contribution of these solutes was
      about 50% of the total Psi (s) (A) preveraison, but increased to about 75% as
      fructose and glucose accumulated during ripening. The contribution of the
      estimated matric potential to apoplast water potential decreased during
      development and was only 1.5% postveraison. We conclude that high concentrations
      of solutes accumulated in the mesocarp apoplast prior to veraison, and that P
      loss was a direct result of decreased Psi (s) (A) . Because Psi (s) (A) decreased
      before veraison, our findings suggest that apoplast solutes play an important
      role in the events of cellular metabolism that lead to the onset of ripening.

PMID- 18317800
TI  - Norepinephrinergic afferents and cytology of the macaque monkey midline,
      mediodorsal, and intralaminar thalamic nuclei.
AB  - The midline and intralaminar thalamic nuclei (MITN), locus coeruleus (LC) and
      cingulate cortex contain nociceptive neurons. The MITN that project to cingulate
      cortex have a prominent innervation by norepinephrinergic axons primarily
      originating from the LC. The hypothesis explored in this study is that MITN
      neurons that project to cingulate cortex receive a disproportionately high LC
      input that may modulate nociceptive afferent flow into the forebrain. Ten
      cynomolgus monkeys were evaluated for dopamine-beta hydroxylase (DBH)
      immunohistochemistry, and nuclei with moderate or high DBH activity were analyzed
      for intermediate neurofilament proteins, calbindin (CB), and calretinin (CR).
      Sections of all but DBH were thionin counterstained to assure precise
      localization in the mediodorsal and MITN, and cytoarchitecture was analyzed with
      neuron-specific nuclear binding protein. Moderate-high levels of DBH
      immunoreactive (ir) axons were generally associated with high densities of CB-ir
      and CR-ir neurons and low levels of neurofilament proteins. The paraventricular,
      superior centrolateral, limitans and central nuclei had relatively high and
      evenly distributed DBH, the magnocellular mediodorsal and paracentral nuclei had
      moderate DBH-ir, and other nuclei had an even and low level of activity. Some
      nuclei also have heterogeneities in DBH-ir that raised questions of functional
      segregation. The anterior multiformis part of the mediodorsal nucleus but not
      middle and caudal levels had high DBH activity. The posterior parafascicular
      nucleus (Pf) was heterogeneous with the lateral part having little DBH activity,
      while its medial division had most DBH-ir axons and its multiformis part had only
      a small number. These findings suggest that the LC may regulate nociceptive
      processing in the thalamus. The well established role of cingulate cortex in
      premotor functions and the projections of Pf and other MITN to the limbic
      striatum suggests a specific role in mediating motor outflow for the LC
      innervated nuclei of the MITN.

PMID- 18317801
TI  - Symptomatic asymmetry in the first six months of life: differential diagnosis.
AB  - Asymmetry in infancy is a clinical condition with a wide variation in appearances
      (shape, posture, and movement), etiology, localization, and severity. The
      prevalence of an asymmetric positional preference is 12% of all newborns during
      the first six months of life. The asymmetry is either idiopathic or symptomatic.
      Pediatricians and physiotherapists have to distinguish symptomatic asymmetry (SA)
      from idiopathic asymmetry (IA) when examining young infants with a positional
      preference to determine the prognosis and the intervention strategy. The majority
      of cases will be idiopathic, but the initial presentation of a positional
      preference might be a symptom of a more serious underlying disorder. The purpose
      of this review is to synthesize the current information on the incidence of SA,
      as well as the possible causes and the accompanying signs that differentiate SA
      from IA. This review presents an overview of the nine most prevalent disorders in
      infants in their first six months of life leading to SA. We have discovered that
      the literature does not provide a comprehensive analysis of the incidence,
      characteristics, signs, and symptoms of SA. Knowledge of the presented clues is
      important in the clinical decision making with regard to young infants with
      asymmetry. We recommend to design a valid and useful screening instrument.

PMID- 18317802
TI  - The health and economic burden of rotavirus disease in Belgium.
AB  - For health economic evaluations of rotavirus vaccination, estimates of the health
      and cost burden of rotavirus are required. Due to differences in health care
      systems and surveillance organisations, this is difficult to achieve by imputing
      estimates from one country to others. This study aimed to estimate the burden of
      rotavirus disease in Belgium. In children younger than 7 years of age, rotavirus
      is predicted to account annually for about 5,600 hospitalisations (676:100,000
      children); 26,800 outpatient, general practitioner and paediatrician visits; and
      about 44,600 episodes for which no medical care is sought. This burden is
      estimated to represent direct costs of 7.7 million Euro and indirect costs of
      12.8 million Euro. Rotavirus disease causes a substantial health and economic
      burden in Belgium.

PMID- 18317803
TI  - Novel BTK mutation presenting with vaccine-associated paralytic poliomyelitis.
AB  - Oral polio vaccine (OPV) has been used safely and efficiently for more than 40
      years in preventive medicine. Vaccine-associated paralytic poliomyelitis (VAPP)
      is a rare adverse event of OPV due to reversion of the vaccine strain virus to a
      neurovirulent strain. VAPP can occur in healthy recipients or their close
      contacts. However, persons with primary humoral immunodeficiencies are at a much
      higher risk. X-linked agammaglobulinemia (XLA) is a prototypic humoral deficiency
      caused by mutations in the Bruton's tyrosine kinase (BTK) gene. In addition to
      susceptibility to bacterial infections, patients with XLA are especially prone to
      enteroviruses. Here, we describe the occurrence of VAPP in a 15-month old Iranian
      boy. The child had received four doses of OPV, administered at birth, 2, 4, and 6
      months of age. The patient's infectious history was unremarkable. Laboratory
      evaluation revealed low levels of immunoglobulin G and CD19(+) B cells of less
      than 1% of the lymphocyte population. A novel insertion (c.685_686insTTAC) in the
      SH3 domain of the BTK gene was detected as the underlying cause. Immunodeficient
      recipients of OPV can excrete poliovirus vaccine strains for a long period and
      are at risk of developing flaccid paralysis. They could also serve as a source of
      reverted virulent poliovirus to be reintroduced into the general population. This
      patient presented for the first time with VAPP, without any history of other
      major infections in 15 months. This suggests that a negative history for
      recurrent infections does not exclude the presence of a primary defect in the
      immune system.

PMID- 18317804
TI  - Resolution of pathologic Q wave, left ventricular dysfunction and mitral
      regurgitation after dual coronary repair of the anomalous origin of the left
      coronary artery from the pulmonary artery.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA)
      is a rare congenital cardiac defect that usually presents as dilated
      cardiomyopathy in infancy. From 1984 to 2005, 13 (five males and eight females,
      0.13%) out of 9,950 patients with congenital heart disease were identified as
      ALCAPA at our institute. Corrective surgery was performed at a median age of 9
      months (range: 2 months to 5 years). Eleven patients underwent direct
      reimplantation of the left coronary artery (LCA) to the aorta, while two received
      extrapulmonary baffling. The overall survival rate was 92%. Only one patient died
      5 months after reimplantation of the LCA due to acute myocardial ischaemia. Left
      ventricular ejection fraction (LVEF) was significantly lower in the eight (62%)
      patients operated during infancy than in those operated beyond 5 months (median:
      35% vs. 75%). Left ventricle function was normalised in 11 patients (85%). Among
      the eight patients without concomitant mitral annuloplasty, mitral regurgitation
      (MR) improved to a mild or trivial degree in six patients and remained at the pre
      operative level in two patients. Pathologic Q wave was noted in 11 patients,
      which eventually regressed in all except two cases. The median interval of
      recovery was 16 days, 6 months and 24 months for MR, LVEF and electrocardiogram
      (ECG) changes, respectively. In conclusion, ALCAPA is also a rare disease in
      Asian countries, such as Taiwan. The subsequent recovery of MR, left ventricular
      (LV) function and even pathologic Q wave can be expected after dual coronary
      repair, regardless of the age at repair.

PMID- 18317805
TI  - Selection of reference genes for real-time PCR in human hepatocellular carcinoma
      tissues.
AB  - AIMS: To investigate the most suitable housekeeping genes for quantifying a
      change in mRNA expression levels due to hepatitis virus B related hepatocellular
      carcinoma (HCC). METHODS: Expression of mRNA encoding ACTB, GAPDH, B2M, HPRT and
      TBP was measured using quantitative reverse transcription polymerase chain
      reaction (qRT-PCR) in matched malignant and non-malignant tissues obtained from
      65 non-treated HCCs. The software programs geNorm and NormFinder were used to
      ascertain the most suitable reference gene combination. RESULTS: All candidate
      genes showed significantly different expression between malignant and non
      malignant samples. GAPDH and ACTB, genes most frequently used for normalization,
      were heavily regulated during HCC carcinogenesis and progression. B2M expression
      levels varied with hepatitis infection status. The combination of HPRT and TBP
      expression levels were the most stable, regardless of differences in tumor stage
      and cirrhotic and malignancy status. CONCLUSIONS: It is necessary to select
      reference genes based on tissue and disease specific expression profile and to
      further identify novel reference genes with greater expression stability for use
      in HBV related HCC gene expression studies.

PMID- 18317806
TI  - Establishment of a nude mouse transplantable model of a human malignant fibrous
      histiocytoma of the mandible with high metastatic potential to the lung.
AB  - Malignant fibrous histiocytoma (MFH) is one of the highest-grade sarcomas arising
      in bone and soft tissue. Its prognosis is poor because of chemoresistance and
      high metastatic potential to various organs. Few cases arising of MFH of the
      mandible or oral cavity have been documented. We established a tumor line in nude
      mice (MFH-N), which was derived from human MFH of the mandible and examined the
      characteristics of this tumor line. Histologically, MFH-N was identical to the
      original tumor and showed a storiform-pleomorphic pattern, but had low metastatic
      potential. Immunohistochemically, both the original and xenografted tumors
      expressed vimentin, S-100, alpha-SMA, and histiocytic marker CD68. Lysozyme was
      expressed by the original tumor, but only sporadically by the xenografted tumor.
      RT-PCR analysis demonstrated human beta-actin in this tumor line, indicating the
      human origin. In a parallel experiment, we established a new MFH cell line (MFH
      NC) from MFH-N. Tumor cells inoculated into the flanks and submandibular region
      of nude mice developed into tumors histologically similar to MFH-N and the
      original tumor; multiple lung metastases were detected approximately 5 months
      after inoculation. The expression levels of various metastasis-related molecules
      differed between MFH-N and MFH-NC on Western blotting. In MFH-NC, the expressions
      of MMP7, MMP9, MT1-MMP, CXCR4, COX-2 and integrin alpha4 were up-regulated, while
      those of MMP2 and TIMP1 were down-regulated. Expression of TIMP2, integrinalphaL
      and sialyl lewis X were not detected in either line. Our findings suggest that
      the MFH-N tumor line transplantable in nude mice is a useful model for studying
      the biological behavior of MFH.

PMID- 18317807
TI  - Helminth parasites of stellate sturgeon Acipenser stellatus Pallas, 1771 and
      Persian sturgeon Acipenser persicus Borodin, 1897 (Pisces: Acipenseridae) from
      the South-East Caspian Sea.
AB  - A total of 182 specimens of two sturgeon species, stellate sturgeon Acipenser
      stellatus (N=112) and Persian sturgeon Acipenser persicus (N=70), from three
      coastal stations in the South-East Caspian Sea were examined for endohelminth
      parasites. Four helminth species were recorded: Cucullanus sphaerocephala
      (Nematoda: Cucullanidae) and Skrjabinopsolus semiarmatus (Digenea:
      Acanthocolpidae), found in both host species, and Leptorhynchoides plagicephalus
      (Acanthocephala: Rhadinorhynchidae) and Amphilina foliacea (Cestodaria:
      Amphilinidae), found only in A. stellatus. The most abundant parasites were C.
      sphaerocephala and S. semiarmatus in A. persicus and A. stellatus, respectively.
      Canonical discriminant analysis was applied for separating host species using
      parasite numbers data, Brillouin index of diversity, and species richness. By
      this means, 83% of the hosts were assigned to their correct a priori groups. The
      different feeding habits and habitat preferences of the two hosts are probably
      the major factors accounting for the difference in their parasite burdens.

PMID- 18317808
TI  - Role of Mycobacterium vaccae in the protection induced by first generation
      Leishmania vaccine against murine model of leishmaniasis.
AB  - Various Leishmania antigens showed to induce protection when used with IL-12 as
      an adjuvant in an animal model of leishmaniasis. Limitations in using IL-12
      justify searching for an appropriate adjuvant to accelerate induction of a Th1
      type immune response and protection. In this study, the role of Mycobacterium
      vaccae as an adjuvant mixed with either autoclaved Leishmania major (ALM) or
      freeze-thawed-killed L. major (KLM) in increasing protection in susceptible and
      resistant mice was studied. Nineteen groups of BALB/c and 19 groups of C57BL/6
      mice, ten mice per group, were immunized three times in 45 days interval with
      different doses of either KLM or ALM alone or mixed with either BCG or different
      doses of M. vaccae. Immunized groups of mice and PBS-injected control group were
      challenged with 2 x 10(6) promastigotes of L. major at the base of the tail. The
      evolution of the lesion was monitored, and the size of the lesion was measured
      and recorded weekly. Anti-Leishmania total IgG Ab was titrated before and after
      challenge. The results showed that immunization of either susceptible or
      resistant mice with KLM or ALM mixed with low dose of M. vaccae increased
      protection defined by significantly smaller ulcer size in immunized mice compared
      with the PBS-injected control group.

PMID- 18317809
TI  - Transcriptomics and adaptive genomics of the asymptomatic bacteriuria Escherichia
      coli strain 83972.
AB  - Escherichia coli strains are the major cause of urinary tract infections in
      humans. Such strains can be divided into virulent, UPEC strains causing
      symptomatic infections, and asymptomatic, commensal-like strains causing
      asymptomatic bacteriuria, ABU. The best-characterized ABU strain is strain 83972.
      Global gene expression profiling of strain 83972 has been carried out under seven
      different sets of environmental conditions ranging from laboratory minimal medium
      to human bladders. The data reveal highly specific gene expression responses to
      different conditions. A number of potential fitness factors for the human urinary
      tract could be identified. Also, presence/ absence data of the gene expression
      was used as an adaptive genomics tool to model the gene pool of 83972 using
      primarily UPEC strain CFT073 as a scaffold. In our analysis, 96% of the
      transcripts filtered present in strain 83972 can be found in CFT073, and genes on
      six of the seven pathogenicity islands were expressed in 83972. Despite the very
      different patient symptom profiles, the two strains seem to be very similar.
      Genes expressed in CFT073 but not in 83972 were identified and can be considered
      as virulence factor candidates. Strain 83972 is a deconstructed pathogen rather
      than a commensal strain that has acquired fitness properties.

PMID- 18317810
TI  - The barley plastome mutant CL2 affects expression of nuclear and chloroplast
      housekeeping genes in a cell-age dependent manner.
AB  - The barley plastome mutant CL2 (cytoplasmic line 2) carries a point mutation in
      the infA gene, a homologue of the bacterial gene for the conserved translation
      initiator factor 1 (IF1). The function of infA in plastids is not known. The
      mutation in CL2 leads to a temporal chlorophyll deficiency in the primary leaf
      blade that is normalised in the basal and middle parts during further
      development. We have compared the expression of selected nuclear and plastid
      genes in different parts of primary leaves of CL2 and wild-type and found no
      indication for an adverse effect of the mutation on plastidial transcription. We
      observed an enhanced expression of RpoTp (encoding the phage-type nuclear-encoded
      plastid RNA polymerase) suggested to be caused by retrograde plastid signalling.
      Decreased amounts of plastid rRNA in basal and top sections are in agreement with
      the idea that the mutation in infA leads to a time- and position-dependent defect
      of plastid translation that causes a delay in plastid development. The
      normalisation of the phenotype in the middle section of CL2 leaves correlates
      with wild-type levels of chloroplast 16S rRNA and RbcL and increased expression
      of plastid housekeeping genes. The normalisation was not observed in cells at the
      tip of CL2 leaves suggesting different ways of regulating chloroplast development
      in cells at the tip of primary barley leaves as compared with other leaf
      sections.

PMID- 18317811
TI  - Evolutionary analysis of genes of two pathways involved in placental malaria
      infection.
AB  - Placental malaria is a special form of malaria that causes up to 200,000 maternal
      and infant deaths every year. Previous studies show that two receptor molecules,
      hyaluronic acid and chondroitin sulphate A, are mediating the adhesion of
      parasite-infected erythrocytes in the placenta of patients, which is believed to
      be a key step in the pathogenesis of the disease. In this study, we aimed at
      identifying sites of malaria-induced adaptation by scanning for signatures of
      natural selection in 24 genes in the complete biosynthesis pathway of these two
      receptor molecules. We analyzed a total of 24 Mb of publicly available
      polymorphism data from the International HapMap project for three human
      populations with European, Asian and African ancestry, with the African
      population from a region of presently and historically high malaria prevalence.
      Using the methods based on allele frequency distributions, genetic
      differentiation between populations, and on long-range haplotype structure, we
      found only limited evidence for malaria-induced genetic adaptation in this set of
      genes in the African population; however, we identified one candidate gene with
      clear evidence of selection in the Asian population. Although historical exposure
      to malaria in this population cannot be ruled out, we speculate that it might be
      caused by other pathogens, as there is growing evidence that these molecules are
      important receptors in a variety of host-pathogen interactions. We propose to use
      the present methods in a systematic way to help identify candidate regions under
      positive selection as a consequence of malaria.

PMID- 18317812
TI  - Anatomical evidence for ileal Peyer's patches innervation by enteric nervous
      system: a potential route for prion neuroinvasion?
AB  - We have examined the innervation of the gut-associated lymphoid system of the
      sheep ileum, with a view to identifying potential sites for neuroinvasion by
      pathogens, such as prions (PrP(Sc)). Special attention has been paid to the
      follicles of Peyer's patches (PPs), which are major sites of PrP(Sc) accumulation
      during infection. Evidence exists that the enteric nervous system, together with
      the parasympathetic and sympathetic pathways projecting to the intestine, are
      important for PrP(Sc) entry into the central nervous system. Thus, PrP(Sc) might
      move from PPs to the neurons and nerve fibres that innervate them. We
      investigated, by immunohistochemistry and retrograde tracing (DiI) from the
      follicles, the distribution and phenotype of enteric neurons innervating the
      follicles. Antibodies against protein gene product 9.5, tyrosine hydroxylase,
      dopamine beta hydroxylase, choline acetyltransferase, calbindin (CALB),
      calcitonin gene-related peptide (CGRP), and nitric oxide synthase were used to
      characterise the neurons. Immunoreactivity for each of these was observed in
      fibres around and inside PP follicles. CGRP-immunoreactive fibres were mainly
      seen at the follicular dome. Retrograde tracing revealed submucosal neurons that
      contributed to the innervation of PPs, including Dogiel type II neurons and
      neurons immunoreactive for CALB and CGRP. The major source of the adrenergic
      fibres are the sympathetic ganglia. Our results thus suggest that enteric and
      sympathetic neurons are involved during the first stage of neuroinvasion, with
      neurons connecting to them acting as potential carriers of PrP(Sc) to the central
      nervous system.

PMID- 18317813
TI  - Small interfering RNA of alkaline phosphatase inhibits matrix mineralization.
AB  - To investigate the cascade of matrix mineralization, cells expressing high and
      low alkaline phosphatase (ALP) were separated from human osteoblast-like (HOS)
      cells by fluorescence-activated cell sorting with an ALP antibody. After these
      cells had been recloned from single cells and then cultured under osteogenic
      conditions, high-ALP-expressing HOS (H-HOS) cells showed matrix mineralization,
      but low-ALP-expressing HOS (L-HOS) cells did not. The interaction among
      osteogenic-related genes, such as runt-related transcription factor 2 (RUNX2),
      collagen type I alpha1 chain (COL1A1), tissue non-specific ALP, and osteocalcin
      (OCN), is well known as being related to matrix mineralization. Quantitative real
      time polymerase chain reaction revealed that the gene expression of ALP was
      higher in H-HOS cells than in L-HOS, whereas the gene expression of RUNX2,
      COL1A1, and OCN was lower in H-HOS cells than in L-HOS cells. When small
      interfering RNAs (siRNAs) of these osteogenic-related genes were introduced into
      H-HOS cells by transfection, only ALP siRNA inhibited matrix mineralization.
      Furthermore, the expression of not only the ALP gene, but also the COL1A1 and
      RUNX2 genes was influenced by the inhibition of ALP, although the expression of
      OCN was not affected by the inhibition of ALP. We have been able to confirm that
      the ALP gene is a strong candidate as the trigger of matrix mineralization. These
      results indicate the usefulness of cloned osteogenic cells in investigating the
      molecular mechanisms of matrix mineralization, the function of which can be
      modulated by using a variety of siRNAs.

PMID- 18317814
TI  - Biochemical analysis of selenoprotein expression in brain cell lines and in
      distinct brain regions.
AB  - Selenium is present in various biologically important selenoproteins. The
      preferential incorporation of selenium into the brain indicates its significance
      for this organ, but so far knowledge concerning the cerebral selenoproteome is
      scarce. We therefore investigated the expression of selenoproteins in various
      regions of the rat brain, various subcellular fractions and several brain cell
      lines by (75)Se-labelling, gel electrophoretic separation and autoradiography,
      with the (75)Se tracer as the selenoprotein marker. Quantitative evaluation of
      the labelled proteins in selenium-deficient rats revealed information regarding
      preferentially supplied selenoproteins and their distribution; 21 selenoproteins
      could be distinguished, among them a novel or modified 15-kDa selenoprotein
      enriched in the cerebellum cytosol. The selenoproteins differed in the degree of
      their expression among the brain regions and within a region among the
      subcellular fractions. Some cell-type-specific selenium-containing proteins were
      found in the cell lines. Differences in the distribution patterns between mono
      cultured and co-cultured endothelial cells and astrocytes showed that mediators
      produced by other cells could affect the selenoprotein expression of a specific
      cell-type. This effect might play a role in the uptake and distribution of
      selenium in the brain but could also be of significance in the selenium
      metabolism of other tissues.

PMID- 18317815
TI  - Animal movement in dynamic landscapes: interaction between behavioural strategies
      and resource distributions.
AB  - Most ecological and evolutionary processes are thought to critically depend on
      dispersal and individual movement but there is little empirical information on
      the movement strategies used by animals to find resources. In particular, it is
      unclear whether behavioural variation exists at all scales, or whether
      behavioural decisions are primarily made at small spatial scales and thus broad
      scale patterns of movement simply reflect underlying resource distributions. We
      evaluated animal movement responses to variable resource distributions using the
      grey teal (Anas gracilis) in agricultural and desert landscapes in Australia as a
      model system. Birds in the two landscapes differed in the fractal dimension of
      their movement paths, with teal in the desert landscape moving less tortuously
      overall than their counterparts in the agricultural landscape. However, the most
      striking result was the high levels of individual variability in movement
      strategies, with different animals exhibiting different responses to the same
      resources. Teal in the agricultural basin moved with both high and low
      tortuosity, while teal in the desert basin primarily moved using low levels of
      tortuosity. These results call into question the idea that broad-scale movement
      patterns simply reflect underlying resource distributions, and suggest that
      movement responses in some animals may be behaviourally complex regardless of the
      spatial scale over which movement occurs.

PMID- 18317816
TI  - Predators reverse the direction of density dependence for juvenile salmon
      mortality.
AB  - The effect of predators on prey populations depends on how predator-caused
      mortality changes with prey population density. Predators can enforce density
      dependent prey mortality and contribute to population stability, but only if they
      have a positive numerical or behavioral response to increased prey density.
      Otherwise, predator saturation can result in inversely density-dependent
      mortality, destabilizing prey populations and increasing extinction risk.
      Juvenile salmon and trout provide some of the clearest empirical examples of
      density-dependent mortality in animal populations. However, although juvenile
      salmon are very vulnerable to predators, the demographic effects of predators on
      juvenile salmon are unknown. We tested the interactive effects of predators and
      population density on the mortality of juvenile Atlantic salmon (Salmo salar)
      using controlled releases of salmon in natural streams. We introduced newly
      hatched juvenile salmon at three population density treatments in six study
      streams, half of which contained slimy sculpin (Cottus cognatus), a common
      generalist predator (18 release sites in total, repeated over two summers).
      Sculpin reversed the direction of density dependence for juvenile salmon
      mortality. Salmon mortality was density dependent in streams with no sculpin, but
      inversely density dependent in streams where sculpin were abundant. Such predator
      mediated inverse density dependence is especially problematic for prey
      populations suppressed by other factors, thereby presenting a fundamental
      challenge to persistence of rare populations and restoration of extirpated
      populations.

PMID- 18317817
TI  - Determinants of abundance and effects of blood-sucking flying insects in the nest
      of a hole-nesting bird.
AB  - Compared to non-flying nest-dwelling ectoparasites, the biology of most species
      of flying ectoparasites and its potential impact on avian hosts is poorly known
      and rarely, if ever, reported. In this study we explore for the first time the
      factors that may affect biting midge (Diptera: Ceratopogonidae) and black fly
      (Diptera: Simuliidae) abundances in the nest cavity of a bird, the hole-nesting
      blue tit Cyanistes caeruleus, and report their effects on adults and nestlings
      during reproduction. The abundance of biting midges was positively associated
      with nest mass, parental provisioning effort and abundance of blowflies and black
      flies, while negatively associated with nestling condition. Furthermore, a
      medication treatment to reduce blood parasitaemias in adult birds revealed that
      biting midges were more abundant in nests of females whose blood parasitaemias
      were experimentally reduced. This finding would be in accordance with these
      insect vectors attacking preferentially uninfected or less infected hosts to
      increase their own survival. The abundance of black flies in the population was
      lower than that of biting midges and increased in nests with later hatching
      dates. No significant effect of black fly abundance on adult or nestling
      condition was detected. Blood-sucking flying insects may impose specific,
      particular selection pressures on their hosts and more research is needed to
      better understand these host-parasite associations.

PMID- 18317818
TI  - Correlation of acid-induced conformational transition of ferricytochrome c with
      cyanide binding kinetics.
AB  - A relation between pH-induced conformational transitions of horse heart
      ferricytochrome c and the kinetics of external ligand coordination to heme iron
      was investigated by optical spectroscopy, circular dichroism and viscometry. The
      dependencies of both the association, k (a), and dissociation rate constants of
      cyanide binding on pH were determined from kinetic measurements. The association
      rate constant exhibits a bell-shaped form of dependence on pH in the region where
      this protein unfolds. The maximum of the dependence of k (a) on pH is found to be
      coincident with the pK values of conformational transitions of ferricytochrome c
      in solutions with both low and high ionic strengths. This observation is
      explained in terms of ferricytochrome c unfolding, which is characterized by two
      processes: the gradual opening of the heme crevice accompanied by the detachment
      of the axial Met80 and its replacement with a water molecule. The former process
      enhances the rate, whereas the latter results in the inhibition of the rate of
      cyanide binding.

PMID- 18317819
TI  - Sigma-hole bonding between like atoms; a fallacy of atomic charges.
AB  - Covalently bonded atoms, at least in Groups V-VII, may have regions of both
      positive and negative electrostatic potentials on their surfaces. The positive
      regions tend to be along the extensions of the bonds to these atoms; the origin
      of this can be explained in terms of the sigma-hole concept. It is thus possible
      for such an atom in one molecule to interact electrostatically with its
      counterpart in a second, identical molecule, forming a highly directional
      noncovalent bond. Several examples are presented and discussed. Such "like-like"
      interactions could not be understood in terms of atomic charges assigned by any
      of the usual procedures, which view a bonded atom as being entirely positive or
      negative.

PMID- 18317820
TI  - Cervical necrotizing fasciitis: 8-years' experience of microbiology.
AB  - Cervical necrotizing fasciitis (CNF) is a life-threatening complication of
      pharyngeal or dental infections. The aim of this paper was to investigate whether
      dental or pharyngeal source result from different pathogen(s) in CNF and whether
      antibiotics, given before admission, influence the antimicrobial resistance of
      pathogens. In 152 CNF patients, Streptococcus milleri group and Prevotella
      species were the predominant isolates, frequently copathogens, mostly in dental
      CNF samples. Penicillin and clindamycin resistance were observed in 39% and 37%
      of cases, respectively, independently of any previous antibiotic therapy. Thus, a
      combined aerobe-anaerobe infection may have a synergistic effect, which allows
      the infection to spread in cervical tissues.

PMID- 18317821
TI  - Clinical outcomes and risk factors of community-acquired pneumonia caused by gram
      negative bacilli.
AB  - To identify specific risk factors and clinical outcomes of community-acquired
      pneumonia (CAP) caused by gram-negative bacilli (GNB), we compared the clinical
      features and outcomes of patients with CAP due to GNB with those of patients with
      non-GNB pneumonia. We performed a prospective observational study of 912 cases of
      adult CAP in Asian countries from January 2002 to December 2004. Systemic
      laboratory evaluation for determining the etiology and clinical evaluation were
      performed. Of 912 cases with CAP, 93 (10.1%) cases were caused by GNB: 59 with K.
      pneumoniae, 25 P. aeruginosa, 7 Enterobacter species, 1 Acinetobacter baumannii,
      and 1 Serratia marcescens. CAP caused by GNB was more frequently associated with
      septic shock, malignancy, cardiovascular diseases, smoking, hyponatremia, and
      dyspnea, according to multivariate analysis (P < 0.05). Overall 30-day mortality
      rate was 7.3% (65/885). Mortality was significantly higher in the GNB group than
      in the non-GNB group [18.3% (17/93) vs. 6.1% (48/792); P < 0.001]. GNB as a
      causative microorganism was found to be one of the independent risk factors for
      mortality (adjusted OR = 2.63, 95% CI 1.02-6.78, P = 0.046) with nursing home
      residence, mechanical ventilation, cardiovascular disease, respiratory rate >
      30/min, and hyponatremia (all P < 0.05). GNB was not only a frequent etiology of
      severe CAP but also an independent risk factor for mortality. Data suggest that
      an initial empirical antimicrobial coverage of GNB including P. aeruginosa should
      be seriously considered in cases of severe pneumonia, especially in patients with
      underlying malignancy, underlying cardiovascular diseases, smoking, septic shock,
      and hyponatremia.

PMID- 18317822
TI  - Correct identification and discrimination between Campylobacter jejuni and C.
      coli by a standardized hippurate test and species-specific polymerase chain
      reaction.
AB  - Hippurate hydrolysis test results of 240 Campylobacter strains were compared with
      those of two multiplex polymerase chain reaction (PCR) assays. Of the 152 strains
      identified in Finnish clinical microbiology routine laboratories as C. coli
      (hippurate-negative), 11% were C. jejuni (hippurate-positive) by standardized
      hippurate test and 39% by PCR in the reference laboratory. Two of the 81
      hippurate-positive strains were identified as C. coli. Standardizing the
      hippurate test by determining minimum and maximum turbidity limits (McFarland 6
      and McFarland 10, OD(450) values 0.8 and 1.4, respectively) for the bacterial
      cell suspension eliminated the false-positive results, but 32% of the 145
      hippurate-negative strains were still identified as C. jejuni by PCR. The species
      identification of Campylobacter isolates in Finland could be improved by using a
      standardized hippurate hydrolysis test to identify hippurate-positive C. jejuni
      and testing hippurate-negative strains by molecular methods. This would also
      improve the epidemiological data on this important zoonotic pathogen.

PMID- 18317823
TI  - Quick and reliable galactomannan detection in crude minced lung specimens from
      haematological patients with suspected invasive fungal infection: results from a
      case series.
AB  - Invasive aspergillosis (IA) is the leading direct or contributory cause of death
      in patients with haematological malignancies. Early diagnosis remains difficult
      and often elusive due the heterogeneity of clinical presentations and the low
      sensitivity of both histological examination and cultures of specimens obtained
      from patients at risk. We report two cases of IA, both of which lacked both
      histological and cultural evidence of IA from pulmonary specimens. In both
      patients, detection of galactomannan (GM) by enzyme immunoassay (EIA) on
      pulmonary tissue homogenates led to the diagnosis of IA, which was confirmed by
      Aspergillus DNA (real time PCR). In conclusion, we provide preliminary evidence
      that lung homogenates may be prepared for GM EIA assays, which may contribute to
      quick diagnosis of IA on otherwise negative samples. We feel that our results
      open up the opportunity of a prospective and comparative evaluation of this
      diagnostic technique.

PMID- 18317824
TI  - Dormancy in potato tuber meristems: chemically induced cessation in dormancy
      matches the natural process based on transcript profiles.
AB  - Meristem dormancy in perennial plants is a developmental process that results in
      repression of metabolism and growth. The cessation of dormancy results in rapid
      growth and should be associated with the production of nascent transcripts that
      encode for gene products controlling for cell division and growth. Dormancy
      cessation was allowed to progress normally or was chemically induced using
      bromoethane (BE), and microarray analysis was used to demonstrate changes in
      specific transcripts in response to dormancy cessation before a significant
      increase in cell division. Comparison of normal dormancy cessation to BE-induced
      dormancy cessation revealed a commonality in both up and downregulated
      transcripts. Many transcripts that decrease as dormancy terminates are inducible
      by abscisic acid particularly in the conserved BURP domain proteins, which
      include the RD22 class of proteins and in the storage protein patatin.
      Transcripts that are associated with an increase in expression encoded for
      proteins in the oxoglutarate-dependent oxygenase family. We conclude that BE
      induced cessation of dormancy initiates transcript profiles similar to the
      natural processes that control dormancy.

PMID- 18317826
TI  - Predicting enzyme behavior in nonconventional media: correlating nitrilase
      function with solvent properties.
AB  - The insolubility of nitrile substrates in aqueous reaction mixture decreases the
      enzymatic reaction rate. We studied the interaction of fourteen water miscible
      organic solvents with immobilized nitrile hydrolyzing biocatalyst. Correlation of
      nitrilase function with physico-chemical properties of the solvents has allowed
      us to predict the enzyme behavior in such non-conventional media. Addition of
      organic solvent up to a critical concentration leads to an enhancement in
      reaction rate, however, any further increase beyond the critical concentration in
      the latter leads to the decrease in catalytic efficiency of the enzyme, probably
      due to protein denaturation. The solvent dielectric constant (epsilon) showed a
      linear correlation with the critical concentration of the solvent used and the
      extent of nitrile hydrolysis. Unlike alcohols, the reaction rate in case of
      aprotic solvents could be linearly correlated to solvent log P. Further, kinetic
      analysis confirmed that the affinity of the enzyme for its substrate (K (m)) was
      highly dependent upon the aprotic solvent used. Finally, the prospect of solvent
      engineering also permitted the control of enzyme enantioselectivity by regulating
      enantiomer traffic at the active site.

PMID- 18317827
TI  - Methyl alpha-D-glucopyranoside enhances the enzymatic activity of recombinant
      beta-galactosidase inclusion bodies in the araBAD promoter system of Escherichia
      coli.
AB  - In this study, we utilized a catabolite repressor to improve the enzymatic
      activity of recombinant beta-galactosidase inclusion bodies (IBs) produced in
      Escherichia coli under the araBAD promoter system. Specifically, we employed
      methyl alpha-D: -glucopyranoside (alpha-MG) to lower the transcription rate of
      the beta-galactosidase structural gene. In deepwell microtiter plate and lab
      scale fermentor culture systems, we demonstrated that the addition of alpha-MG
      after induction improved the specific beta-galactosidase production, even though
      beta-galactosidase was still produced as an IB. Particularly, the addition of
      0.0025% alpha-MG led to the most significant increase in the specific activity of
      the beta-galactosidase. Interestingly, the beta-galactosidase IBs obtained in the
      presence of 0.0025% alpha-MG were more loosely packed, as determined by IB
      solubilization in guanidine hydrochloride solution. We propose that the reduced
      gene transcription rate was responsible for the increased specific beta
      galactosidase activity and the loose packing that characterized the IBs produced
      in the presence of alpha-MG. This principle could be applied throughout the
      enzyme bioprocessing industry in order to enhance the activity of aggregate-prone
      enzymes within IBs.

PMID- 18317828
TI  - Quantitative study of interactions between Saccharomyces cerevisiae and
      Oenococcus oeni strains.
AB  - This study examines the interactions that occur between Saccharomyces cerevisiae
      and Oenococcus oeni strains during the process of winemaking. Various
      yeast/bacteria pairs were studied by applying a sequential fermentation strategy
      which simulated the natural winemaking process. First, four yeast strains were
      tested in the presence of one bacterial strain leading to the inhibition of the
      bacterial component. The extent of inhibition varied widely from one pair to
      another and closely depended on the specific yeast strain chosen. Inhibition was
      correlated to weak bacterial growth rather than a reduction in the bacterial
      malolactic activity. Three of the four yeast strains were then grown with another
      bacteria strain. Contrary to the first results, this led to the bacterial
      stimulation, thus highlighting the importance of the bacteria strain. The
      biochemical profile of the four yeast fermented media exhibited slight variations
      in ethanol, SO(2) and fatty acids produced as well as assimilable consumed
      nitrogen. These parameters were not the only factors responsible for the
      malolactic fermentation inhibition observed with the first bacteria strain. The
      stimulation of the second has not been reported before in such conditions and
      remains unexplained.

PMID- 18317829
TI  - Analysis and comparison of the bacterial community in fermented grains during the
      fermentation for two different styles of Chinese liquor.
AB  - Bacterial populations in fermented grains during fermentation may play important
      roles in Chinese liquor flavor. PCR-based denaturing gradient gel electrophoresis
      (DGGE) and 16S rRNA gene library analysis were performed to analyze the bacterial
      community structure of two styles of liquor. The results of DGGE profiles showed
      that bacterial diversity decreased with the fermentation process and
      Lactobacillus acetotolerans became the predominant species at the end of the
      fermentation. But the obvious differences of bacterial community appeared in the
      middle stage of two styles of liquor fermentation, in which the different
      upstream production techniques were used. Moreover, 16S rRNA gene libraries of
      two styles were constructed. A total of 125 and 107 clones, chosen from two
      libraries, were grouped into 46 and 49 operational taxonomic units (OTUs) by
      amplified ribosomal DNA restriction analysis. According to sequencing results of
      clones, the predominant bacteria in strong aroma style fermented grains were
      those from the class Bacilli, Bacteroidetes, and Clostridia, whereas the
      predominant bacteria in fermented grains of roasted sesame aroma style belonged
      to Bacilli, Flavobacteria, and Gammaproteobacteria. Molecular analysis of the
      bacterial diversity of the liquor fermentation will benefit the analysis of
      important microorganisms playing key roles in the formation of liquor flavor
      components.

PMID- 18317830
TI  - Tumor microvasculature observed using different contrast agents: a comparison
      between Gd-DTPA-Albumin and B-22956/1 in an experimental model of mammary
      carcinoma.
AB  - OBJECTIVE: The aim of this study was to compare a pure macromolecular contrast
      agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent
      (B22956/1) in terms of their capacity to investigate the microvasculature in an
      experimental model of mammary carcinoma. MATERIALS AND METHODS: Tumors were
      induced by subcutaneous injection of 5 x 10(5) BB1 cells into the backs of 5-7
      week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when
      the longest diameter of the tumor was 10.2+/-2.0 mm. DCE-MRI experiments were
      carried out using B22956/1 and (24 h later) Gd-DTPA-albumin. RESULTS: DCE-MRI
      data showed that vasculature in the tumor rim was characterized by greater
      fractional plasma volume and transendothelial permeability than vasculature in
      the tumor core as measured by both contrast agents. Permeability to Gd-DTPA
      albumin in the tumor core was hardly measurable while permeability to B22956/1
      was substantial. Histologically the tumor core showed areas of well vascularized,
      viable tissue surrounded by necrotic regions. CONCLUSIONS: DCE-MRI experiments
      performed with B22956/1 are useful in the investigation of vasculature in those
      tumor regions that are characterized by low permeability to macromolecules.

PMID- 18317831
TI  - Identification of the B subtype of gamma-phospholipase A2 inhibitor from
      Protobothrops flavoviridis serum and molecular evolution of snake serum
      phospholipase A2 inhibitors.
AB  - A cDNA encoding a novel phospholipase A(2) (PLA(2)) inhibitor (PLI) was isolated
      from a Protobothrops flavoviridis snake (Tokunoshima island, Japan) liver cDNA
      library. This cDNA encoded a signal peptide of 19 amino acids followed by a
      mature protein of 181 amino acids. Its N-terminal amino acid sequence was
      completely in accord with that of a PLI, named PLI-II, previously found in P.
      flavoviridis serum. PLI-II showed a high similarity in sequence to the B subtype
      of gammaPLI, denoted gammaPLI-B, isolated from Agkistrodon blomhoffii siniticus
      serum. Thus, PLI-II is P. flavoviridis serum gammaPLI-B. Since PLI-I, previously
      isolated from P. flavoviridis serum, can be assigned as gammaPLI-A, P.
      flavoviridis serum contains both A and B subtypes of gammaPLI. Phylogenetic
      analysis of gammaPLIs from the sera of various kinds of snakes, Elapinae,
      Colubrinae, Laticaudinae, Acanthophiinae, Crotalinae, and Pythonidae, based on
      the amino acid sequences revealed that A and B subtypes of gammaPLIs are clearly
      separated from each other. It was also found that phylogenetic topologies of
      gammaPLIs are in good agreement with speciation processes of snakes. The BLAST
      search followed by analyses with particular Internet search engines of proteins
      with Cys/loop frameworks similar to those of PLI-II and PLI-I revealed that
      gammaPLI-Bs, including PLI-II and PLI-II-like proteins from mammalian sources,
      form a novel PLI-II family which possesses the common Cys/loop frameworks in the
      anterior and posterior three-finger motifs in the molecules. Several lines of
      evidence suggest that PLI-II is evolutionarily ancestral to PLI-I.

PMID- 18317832
TI  - Effluent toxicity test using developmental stages of the marine polychaete
      Hydroides elegans.
AB  - The US Environmental Protection Agency (USEPA) has established a suite of methods
      that use coastal invertebrate species as bioassay organisms to test industrial
      and domestic effluent as well as coastal waters for potential toxicity. Although
      these methods are used globally, the potential of such toxicity tests has not
      been adequately explored for Asian coastal waters. This study describes bioassay
      utilizing the gametes of Hydroides elegans to monitor coastal water quality and
      is based on the sensitivity of H. elegans embryo and larva to different
      concentrations of effluents and water samples collected from different regions of
      east coast of India. Among the water samples collected from different regions,
      seawater from Ennore station showed decrease in percentage of development, and
      25% effluent concentration led to development arrest of H. elegans embryos. The
      different morphological effects produced by effluents clearly reflect the defect
      in early differentiation of embryonic cells. Since fertilization can be inhibited
      in the presence of any xenobiotic, both fertilization and early development can
      be used as a biological indicator for a rapid bioassay to monitor pollution.
      Toxicity tests utilizing early life stages of H. elegans are suitable for the
      assessment of effects produced by low levels of pollutants due to their high
      sensitivity to various contaminants relative to other marine species and also due
      to the relative simplicity of the bioassay.

PMID- 18317833
TI  - Focal liver lesions: contrast-enhanced ultrasound.
AB  - Contrast-enhanced ultrasound (CEUS) represents a significant breakthrough in
      sonography and it is being increasingly used for the evaluation of focal liver
      lesions (FLLs). The unique feature of CEUS of non-invasively assessing in real
      time liver perfusion throughout the vascular phase has led to a dramatic
      improvement in diagnostic accuracy of US in either detection or characterization
      of FLLs, as well as in the guidance and evaluation of response of therapeutic
      procedures. Currently, CEUS is included as a part of the suggested diagnostic
      work-up of FLLs, resulting in a better patient management and cost-effective
      therapy delivering. After a brief description of the basis of different CEUS
      techniques, contrast-enhancement patterns of different types of benign and
      malignant FLLs, among hepatic pseudolesions, will be described and discussed on
      the basis of our experience and literature data. At the same time, the most
      recent concepts and the use of CEUS in different clinical settings will be
      presented.

PMID- 18317834
TI  - Renal involvement of polyarteritis nodosa: CT and MR findings.
AB  - BACKGROUND: To evaluate the imaging findings in patients with renal involvement
      of Polyarteritis nodosa (PN) to diagnose as early as possible. MATERIALS AND
      METHODS: Four patients diagnosed as having PN participated in the present study.
      Two patients underwent abdominal dynamic CT, one underwent only pre- and post
      contrast CT, and the remaining patient underwent only noncontrast CT and MR
      imaging, including dynamic contrast study. RESULTS: The common findings of CT and
      MR imaging were diffuse enlargement, multiple small wedge-shaped less-enhanced
      areas on dynamic contrast study, and indistinctness of the margin between the
      cortex and medulla on equilibrium-phase CT. Renal arteriogram showed multiple
      microaneurysms on arterial phase image in all four cases, and PN was diagnosed.
      The common CT and MR findings of renal involvement of PN mimicked those of
      pyelonephritis, when microaneurysms were not demonstrated. CONCLUSION: The
      differentiation between PN and pyelonephritis on CT and MR imaging is difficult.
      Therefore, the radiologist should be familiar with the imaging findings of renal
      involvement of PN. When PN is suspected, angiography should be performed as early
      as possible to make a definite diagnosis.

PMID- 18317836
TI  - Factors influencing local communities' satisfaction levels with different forest
      management approaches of Kakamega forest, Kenya.
AB  - Satisfaction of communities living close to forests with forest management
      authorities is essential for ensuring continued support for conservation efforts.
      However, more often than not, community satisfaction is not systematically
      elicited, analyzed, and incorporated in conservation decisions. This study
      attempts to elicit levels of community satisfaction with three management
      approaches of Kakamega forest in Kenya and analyze factors influencing them.
      Three distinct management approaches are applied by three different authorities:
      an incentive-based approach of the Forest Department (FD), a protectionist
      approach of the Kenya Wildlife Service (KWS), and a quasi-private incentive-based
      approach of Quakers Church Mission (QCM). Data was obtained from a random sample
      of about 360 households living within a 10-km radius around the forest margin.
      The protectionist approach was ranked highest overall for its performance in
      forest management. Results indicate that households are influenced by different
      factors in their ranking of management approaches. Educated households and those
      located far from market centers are likely to be dissatisfied with all the three
      management approaches. The location of the households from the forest margin
      influences negatively the satisfaction with the protectionist approach, whereas
      land size, a proxy for durable assets, has a similar effect on the private
      incentive based approach of the QCM. In conclusion, this article indicates a
      number of policy implications that can enable the different authorities and their
      management approaches to gain approval of the local communities.

PMID- 18317837
TI  - Formation of reactive oxygen species in lung alveolar cells: effect of vitamin E
      deficiency.
AB  - Reactive oxygen species (ROS) play an important role in the pathogenesis of
      numerous pulmonary diseases. Various mainly membrane-bound ROS-generating
      processes exist in alveolar cells. Vitamin E (vit. E) is the most important
      lipophilic antioxidant. However, the significance of vit. E levels in alveolar
      cells for the regulation of ROS generation has not been investigated so far. We
      demonstrated here that feeding rats with vit. E-depleted nourishment for 5 weeks
      reduced the concentration of vit. E in alveolar type II cell preparations to one
      fifth the amount of control animals. This reduction of vit. E levels was
      associated with an approximately threefold increase in ROS generation in type II
      pneumocytes, lymphocytes, and macrophages. The contribution of individual
      processes of ROS formation in control animals differed strongly among these three
      cell types. However, vit. E deficiency induced predominantly nonmitochondrial ROS
      formation in alveolar cells. Expression and NAD(P)H-oxidase activity in alveolar
      type II cell preparations was not affected by vit. E deficiency. Moreover,
      protein kinase C (PKC) also did not seem to be responsible for vit. E deficiency
      induced ROS generation in alveolar cells. Alimentary vit. E supplementation for 2
      days corrected the cellular vit. E concentration but failed to normalize ROS
      generation in alveolar cells. These data let us assume that alimentary vit. E
      deficiency caused a preferentially nonmitochondria-mediated increase of ROS
      formation in type II pneumocytes, macrophages, and lymphocytes. However, the
      short-term supplementation of vit. E does not reverse these effects.

PMID- 18317838
TI  - Laparoscopic ileal pouch-anal anastomosis in patients with chronic ulcerative
      colitis and primary sclerosing cholangitis: a case-matched study.
AB  - PURPOSE: This study was designed to compare short-term outcomes after
      laparoscopic ileal pouch-anal anastomosis with those of open ileal pouch-anal
      anastomosis in patients with both sclerosing cholangitis and ulcerative colitis.
      METHODS: Sixteen patients with sclerosing cholangitis and ulcerative colitis
      undergoing laparoscopic ileal pouch-anal anastomosis were matched with 16 open
      ileal pouch control subjects by sex, American Society of Anesthesiologists'
      score, age, and body mass index. RESULTS: Operative mortality was zero. Operative
      time was longer in the laparoscopic group (500 +/- 125.8 vs. 381.8 +/- 60.9
      minutes, P = 0.03). Thirty-day complications were not significantly different
      between groups (laparoscopic 25 percent vs. open 43.7 percent, P = 0.26). Length
      of stay was significantly shorter in the laparoscopic group (5.3 +/- 1.3 days vs.
      9.9 +/- 3.3 days open, P < 0.001). Average return of gastrointestinal function
      was 2.5 days in the laparoscopic group and 4.8 days in the open group (P =
      0.001). Time to soft diet was three days in the laparoscopic group and six days
      in the open group (P < 0.001). All patients were alive and all pouches were
      intact at last follow-up. CONCLUSIONS: Laparoscopic ileal pouch-anal anastomosis
      is feasible with apparent safety in patients with primary sclerosing cholangitis,
      resulting in shorter duration of hospital stay and quicker return of
      gastrointestinal function compared with the open procedure with no difference in
      perioperative complications, reoperations, and readmissions.

PMID- 18317839
TI  - Internal resistance may be more important for continence than anal wall tension.

PMID- 18317840
TI  - Intramural formalin injection for rectal ulcer refractory to medical and
      endoscopic treatment.

PMID- 18317841
TI  - Endorectal advancement flaps in the treatment of high anal fistula of
      cryptoglandular origin: full-thickness vs. mucosal-rectum flaps.
AB  - PURPOSE: The treatment of high anal fistula using endorectal advancement flaps
      represents an important technique to attain cure of fistulation and preserve anal
      continence. The creation of the advancement flap may comprise the rectal mucosa
      only or involve the full transection of the rectal wall. A comparison between
      full-thickness flaps and mucosal (partial-thickness) flaps was made to analyze
      the defining elements of successful fistula treatment: recurrence rates and anal
      continence. METHODS: A retrospective review of 54 consecutive patients with high
      anal fistula of cryptoglandular origin was undertaken. Patient risk was
      categorized according to previous anal surgery. Continence was assessed according
      to the Vaizey score. Recurrence rates were recorded in a long-term, complete
      follow-up. RESULTS: Thirty-four patients underwent surgery using a partial
      thickness flap; in 20 patients the full-thickness flap was used. There were no
      major intraoperative or postoperative complications. Continence scores revealed
      significant incontinence in 11.1 percent of all patients. Full transection of the
      rectal wall for flap creation did not pose a threat to continence. Twenty-four
      percent of all patients suffered from a recurrence. Patients with four or more
      previous anal surgeries were at highest risk for failure. A single patient in the
      full-thickness flap group (5 percent) as opposed to 12 patients (35.3 percent) in
      the partial-thickness group suffered from recurrence. CONCLUSION: The comparison
      of partial-thickness to full-thickness endorectal advancement flaps suggests an
      improvement of recurrence rates without higher incontinence rates when a full
      mobilization of the rectal wall is performed.

PMID- 18317842
TI  - Adrenalectomy for clinically isolated metastasis from colorectal carcinoma:
      report of eight cases.
AB  - PURPOSE: Metastasis to the adrenal glands is a relatively frequent finding at
      autopsy. Adrenal metastasis of colorectal carcinoma is rare (14 percent).
      Isolated adrenal metastasis is even rarer, and presents a therapeutic dilemma.
      METHODS: Between 1997 and 2006, eight patients (5 men; mean age, 62 years)
      underwent adrenalectomy for metastasis of colorectal carcinoma. The tumors were
      Stage D in four cases, Stage B in two cases, and Stage C in the remaining two.
      Adjuvant chemotherapy was instituted. RESULTS: All patients were asymptomatic,
      and adrenal metastasis was suspected from an elevated serum level of
      carcinoembryogenic antigen or discovered by computed tomography. Adrenal
      metastases were metachronous in seven patients, with median disease-free interval
      of 3.75 years. At the time of follow-up, one patient remained alive and free of
      disease 12 months after adrenalectomy, one patient was lost to follow-up after 22
      months, and 6 patients have died from malignancy. The mean survival for the
      patients who died was 32 months. CONCLUSIONS: The rarity of isolated adrenal
      metastasis of colorectal carcinoma makes a randomized, prospective trial
      comparing surgery vs. nonsurgical management highly unlikely. Our results provide
      further support for surgical resection of solitary adrenal metastasis, which may
      translate into survival benefit.

PMID- 18317843
TI  - Inter- and intraspecific comparisons of antiherbivore defenses in three species
      of rainforest understory shrubs.
AB  - Plants defend themselves against herbivores and pathogens with a suite of
      morphological, phenological, biochemical, and biotic defenses, each of which is
      presumably costly. The best studied are allocation costs that involve trade-offs
      in investment of resources to defense versus other plant functions. Decreases in
      growth or reproductive effort are the costs most often associated with
      antiherbivore defenses, but trade-offs among different defenses may also occur
      within a single plant species. We examined trade-offs among defenses in closely
      related tropical rain forest shrubs (Piper cenocladum, P. imperiale, and P.
      melanocladum) that possess different combinations of three types of defense: ant
      mutualists, secondary compounds, and leaf toughness. We also examined the
      effectiveness of different defenses and suites of defenses against the most
      abundant generalist and specialist Piper herbivores. For all species examined,
      leaf toughness was the most effective defense, with the toughest species, P.
      melanocladum, receiving the lowest incidence of total herbivory, and the least
      tough species, P. imperiale, receiving the highest incidence. Although variation
      in toughness within each species was substantial, there were no intraspecific
      relationships between toughness and herbivory. In other Piper studies, chemical
      and biotic defenses had strong intraspecific negative correlations with
      herbivory. A wide variety of defensive mechanisms was quantified in the three
      Piper species studied, ranging from low concentrations of chemical defenses in P.
      imperiale to a complex suite of defenses in P. cenocladum that includes ant
      mutualists, secondary metabolites, and moderate toughness. Ecological costs were
      evident for the array of defensive mechanisms within these Piper species, and the
      differences in defensive strategies among species may represent evolutionary
      trade-offs between costly defenses.

PMID- 18317844
TI  - Metasternal gland volatiles and sexual communication in the triatomine bug,
      Rhodnius prolixus.
AB  - Twelve compounds produced by the metasternal glands (MGs) of the triatomine bug
      Rhodnius prolixus were identified by solid phase microextraction (SPME) combined
      with coupled gas chromatography-mass spectrometry (GC-MS) using achiral and
      chiral columns. All substances were ketones or alcohols, and the same compound
      profile was found in the secretions produced by either sex. The most abundant
      compounds were 2-methyl-3-buten-2-ol, (2S)-pentanol, (3E)-2-methyl-3-penten-2-ol,
      and (2R/2S)-4-methyl-3-penten-2-ol. Emission of these compounds was detected more
      frequently from females than males, and females released them more frequently
      during the early hours of the scotophase, the period when sexual activity in this
      species is at its peak. These compounds were also detected in the headspace above
      mating pairs. Finally, the occlusion of the MG orifices of male or female bugs
      with paraffin resulted in a significant decrease in copulation frequency compared
      to sham-operated insects. Together, these data suggest that the MG secretions of
      R. prolixus may be involved in sexual communication.

PMID- 18317845
TI  - Allee effect and control of lake system invasion.
AB  - We consider the model of invasion prevention in a system of lakes that are
      connected via traffic of recreational boats. It is shown that in presence of an
      Allee effect, the general optimal control problem can be reduced to a
      significantly simpler stationary optimization problem of optimal invasion
      stopping. We consider possible values of model parameters for zebra mussels. The
      general N-lake control problem has to be solved numerically, and we show a number
      of typical features of solutions: distribution of control efforts in space and
      optimal stopping configurations related with the clusters in lake connection
      structure.

PMID- 18317846
TI  - Delivery of preventive services to adults aged 50-64: monitoring performance
      using a composite measure, 1997-2004.
AB  - OBJECTIVE: Population-based rates for the delivery of adult vaccinations or
      screenings are typically tracked as individual services. The current approach is
      useful in monitoring progress toward national health goals but does not yield
      information regarding how many U.S. adults receive a combination of preventive
      services routinely recommended based on a person's age and gender. A composite
      measure is important for policymaking, for developing public health
      interventions, and for monitoring the quality of clinical care. During the period
      under study, influenza vaccination was newly recommended (2000) to be routinely
      delivered to adults in this age range. The objective of the study was to compare
      the delivery of routine clinical preventive services to U.S. adults aged 50-64
      years between 1997 and 2004 using a composite measure that includes cancer
      screenings and vaccinations. DESIGN: Data were collected via telephone surveys in
      1997, 2002, and 2004 as part of the Behavioral Risk Factor Surveillance System.
      PARTICIPANTS: The participants were randomly selected adults aged 50-64 years in
      the 50 states and the District of Columbia in the selected years. Sample sizes
      ranged from 24,917 to 77,244. MEASUREMENTS AND MAIN RESULTS: The composite
      measure includes screening for colorectal cancer, cervical cancer, breast cancer,
      and vaccination against influenza (2002 and 2004 only). The composite measure
      quantifies the percentage of adults who are up-to-date with the complete set
      according to recommended schedules. With the inclusion of newly recommended
      influenza vaccination, the percentage of men and women aged 50-64 who were up-to
      date on all selected measures in 2004 was 23.4% and 23.0%, respectively, compared
      with 37.6% and 30.5% in 1997. Without including influenza vaccination, the
      percentage of up-to-date adults aged 50-64 would have risen in 2004 to 50.5%
      (men) and to 44.7% (women). For both sexes, results varied by education,
      race/ethnicity, marriage status, insurance status, health status, and state.
      CONCLUSION: In 2004, the percentage of adults aged 50-64 years receiving
      routinely recommended cancer screenings and influenza vaccination was low with
      fewer than 1 in 4 being up to date.

PMID- 18317848
TI  - How I do it: surgical management of gastrointestinal stromal tumors.
AB  - The surgical management of gastrointestinal stromal tumors (GISTs) has been
      impacted by the development of tyrosine kinase inhibitors (TKIs), advances in
      surgical technique, and a better understanding of the natural history of this
      unique disease. In this article, we review the technical aspects of the
      operations, the expanding role of laparoscopy, and the indications for
      neoadjuvant and neoadjuvant TKI therapy in primary GIST. Furthermore, we explore
      the rationale for and incorporation of surgery in the multidisciplinary
      management of advanced GIST.

PMID- 18317847
TI  - Why don't diabetes patients achieve recommended risk factor targets? Poor
      adherence versus lack of treatment intensification.
AB  - BACKGROUND: Despite the availability of effective hypertension, hyperlipidemia,
      and hyperglycemia therapies, target levels of systolic blood pressure (SBP), LDL
      cholesterol (LDL-c), and hemoglobin A1c control are often not achieved.
      OBJECTIVE: To examine the relative importance of patient medication nonadherence
      versus clinician lack of therapy intensification in explaining above target
      cardiovascular disease (CVD) risk factor levels. DESIGN: Cross-sectional
      assessment. PARTICIPANTS: In 2005, 161,697 Kaiser Permanente Northern California
      adult diabetes patients were included in the study. MEASUREMENT: "Above target"
      was defined as most recent A1c >/=7.0% for hyperglycemia, LDL-c >/=100 mg/dL for
      hyperlipidemia, and SBP >/=130 mmHg for hypertension. Poor adherence was defined
      as medication gaps for >/=20% of days covered for all medications for each
      condition separately. Treatment intensification was defined as an increase in the
      number of drug classes, increased dosage of a class, or a switch to a different
      class within the 3 months before or after notation of above target levels.
      RESULTS: Poor adherence was found in 20-23% of patients across the 3 conditions.
      No evidence of poor adherence with no treatment intensification was found in 30%
      of hyperglycemia patients, 47% of hyperlipidemia patients, and 36% of
      hypertension patients. Poor adherence or lack of therapy intensification was
      evident in 53-68% of patients above target levels across conditions. CONCLUSIONS:
      Both nonadherence and lack of treatment intensification occur frequently in
      patients above target for CVD risk factor levels; however, lack of therapy
      intensification was somewhat more common. Quality improvement efforts should
      focus on these modifiable barriers to CVD risk factor control.

PMID- 18317849
TI  - Treatment of thoracic esophageal anastomotic leaks and esophageal perforations
      with endoluminal stents: efficacy and current limitations.
AB  - BACKGROUND: Intra-thoracic esophageal leakage after esophageal resection or
      esophageal perforation is a life-threatening event. The objective of this non
      randomized observational study was to evaluate the effects of endoluminal stent
      treatment in patients with esophageal anastomotic leakages or perforations in a
      single tertiary care center. METHODS: Thirty-two consecutive patients with an
      intrathoracic esophageal leak, caused by esophagectomy (n = 19), transhiatal
      gastrectomy (n = 3), laparoscopic fundoplication (n = 2), and iatrogenic or
      spontaneous perforation (n = 8), undergoing endoscopic stent treatment were
      evaluated. Hospital stay, mortality and morbidity, sealing rate, extraction
      rates, complications, and long-term effects were measured. RESULTS: Median time
      interval between diagnosis and stent treatment was 3 and 5 days, respectively.
      Eighteen patients had futile surgical closure of the defect before stenting,
      while in 14 patients, stent placement was the primary treatment for leakage.
      Stent placement was technically correct in all patients. Functional sealing was
      achieved in 78%. Mortality was 15.6%. Stent extraction rate was 70%. Overall
      method-related complications occurred in nine patients (28%). CONCLUSIONS:
      Implantation of self-expanding stents after esophageal resection or perforation
      is a feasible and safe procedure with an acceptable morbidity even if used as
      last-choice treatment.

PMID- 18317850
TI  - Laparoscopic local resection based on sentinel node evaluation for early gastric
      cancer: a preliminary report.
AB  - We previously reported that lymphatic mapping using isosulfan blue can be used to
      identify sentinel nodes (SNs). This study was undertaken to evaluate the
      feasibility of using the SN technique in treating early gastric cancer and to
      explore its usefulness for minimal invasive surgery. Twenty-three patients with
      early gastric cancer who underwent SN biopsy were retrospectively evaluated.
      Based on SN evaluation, individualized surgery was performed in five patients
      with T1N0M0 gastric cancer. When pathological examination of frozen sections
      revealed metastasis in SNs, we performed a standard D2 gastrectomy. Laparoscopic
      local resection was applied when the SN biopsy was negative. Our results showed
      that the success rate with SN biopsy in early gastric cancer was 100%, as were
      the accuracy, sensitivity, and specificity. All five patients with early gastric
      cancer had SNs negative for metastases both by frozen section and by
      postoperative pathology. Thus, all these patients underwent laparoscopic local
      resection without extended lymphadenectomy. We conclude that SN biopsy is a
      useful tool to individualize the operative procedure, and laparoscopic local
      resection can be safely performed using SN guidance in selected patients with
      early gastric cancer.

PMID- 18317851
TI  - Quality of life in pancreatic cancer: analysis by stage and treatment.
AB  - In pancreatic cancer patients, survival and palliation of symptoms should be
      balanced with social and functional impairment, and for this reason, health
      related quality of life measurements could play an important role in the decision
      making process. The aim of this work was to evaluate the quality of life and
      survival in 92 patients with different stages of pancreatic adenocarcinoma who
      underwent surgical and/or medical interventions. Patients were evaluated with the
      Functional Assessment of Cancer Therapy questionnaires at diagnosis and follow-up
      (3 and 6 months). At diagnosis, 28 patients (30.5%) had localized disease (group
      1) and underwent surgical resection, 34 (37%) had locally advanced (group 2), and
      30 (32.5%) metastatic disease (Group 3). Improvement in quality of life was found
      in group 1, while in group 3, it decreased at follow-up (p=0.03). No changes in
      quality of life in group 2 were found. Chemotherapy/chemoradiation seems not to
      significantly modify quality of life in groups 2 and 3. Median survival time for
      the entire cohort was 9.8 months (range, 1-24). One-year survival was 74%, 30%,
      and 16% for groups 1, 2, and 3 respectively (p=0.001). Pancreatic cancer
      prognosis is still dismal. In addition to long-term survival benefits, surgery
      impacts favorably quality of life.

PMID- 18317852
TI  - Pregnancy following gastric bypass surgery for morbid obesity: maternal and
      neonatal outcomes.
AB  - BACKGROUND: The purpose of this study was to compare obstetric and neonatal
      outcomes after Roux-en-Y gastric bypass (RYGB) to those in women without such
      surgery. METHODS: Women with RYGB (cases) were matched for maternal age and prior
      cesarean to the next two consecutive women delivering without prior bariatric
      surgery (controls). Pregnancy and newborn outcomes were compared by univariate
      analysis. Outcomes approaching or reaching statistical significance were
      evaluated by conditional logistic regression controlling for maternal body mass
      index (BMI). RESULTS: Despite gastric bypass, the 38 cases were heavier (BMI
      33.4+/-7.3 vs. 28.1+/-6.7 kg/m2, p<0.001) and more often obese (BMI> or =30
      kg/m2, 26/38 (68.4%) vs. 20/76 (26.3%), p<0.001) than controls. Variables
      evaluated by logistic regression adjusted for BMI did not differ in cases versus
      controls, including hypertension (odds ratio [OR] 2.62, 95% confidence interval
      [CI] 0.66-10.50), preterm premature rupture of membranes (OR 0.24, 95% CI 0.02
      3.38), oligohydramnios (OR 2.39, 95% CI 0.66-8.61), and delivery > or =41 weeks
      (OR 0.57, 95% CI 0.11-2.97). DISCUSSION: Obstetric and neonatal outcomes after
      RYGB are similar to those of our general obstetric population.

PMID- 18317853
TI  - Improvement of insulin resistance after obesity surgery: a comparison of gastric
      banding and bypass procedures.
AB  - BACKGROUND: Obesity is a major risk factor for the development of type 2 diabetes
      mellitus (T2DM). Insulin resistance (IR) is considered the pathologic link
      between T2DM and obesity. The mechanism in improving T2DM after bariatric surgery
      remains speculative. This trial assessed the effect of duodenal jejunal exclusion
      on the resolution of IR in gastric banding and gastric bypass procedures.
      METHODS: 660 patients with complete biochemical and clinical data at baseline and
      at 3 years were selected for analysis. There were 197 males and 463 females. The
      mean age was 31.5 years (18-64) and mean BMI was 41.4 (32-77). There were 544
      patients who received laparoscopic gastric bypass, and 116 patients received
      laparoscopic gastric banding. IR was measured by homeostatic model assessment
      (HOMA) index (HI), that can be calculated as HI = plasma glucose (mmol/l) x
      insulin (UI/ml)/22.5. HI was measured before surgery and 1, 3, 6, 12, 24, and 36
      months after surgery. RESULTS: Of the 660 individuals, 517 (78.4%) had IR. The
      mean HI was 7.62 +/- 13.13. The HI was correlated with BMI, waist circumference,
      insulin resistance, hyperlipidemia, inflammatory indicators, and abnormal liver
      enzymes. Before surgery, the HI was 7.92 +/- 14.18 for the bypass group and 6.27
      +/- 6.47 for the banding group. After surgery, the HI began to lower in both
      groups, and this reduction was maintained during follow-up. At 36 months after
      surgery, mean percentage of excess weight loss (%EWL) was 70.5% for the bypass
      group and 41.9% for the banding group. The HI was 1.00 +/- 0.79 for bypass and
      1.51 +/- 1.25 for banding. The bypass patients had a better and faster weight
      reduction, but the HI was similar between the two groups at the same weight
      reduction percentage. CONCLUSION: IR is common in morbidly obese patients. Both
      gastric banding and gastric bypass are effective for the reverse of IR in these
      patients. It seems that the effect is related to the absolute weight loss rather
      than different surgical procedures. There is no duodenal jejunal exclusion effect
      on IR resolution was observed in this study.

PMID- 18317854
TI  - Psychosocial predictors of success after vertical banded gastroplasty.
AB  - BACKGROUND: Psychosocial and behavioral factors contribute to successful
      postoperative outcomes. Patients' psychological factors may be predictive of
      postsurgical adjustment. The identification of these factors would allow
      targeting patients at risk of a poor outcome. Furthermore, it would enable better
      patient selection and preoperative and/or postoperative counseling to improve
      long-term outcomes. Unfortunately, no such consistent and reproducible predictors
      have been found so far. METHODS: The present study investigated in morbid obese
      patients who underwent vertical banded gastroplasty (VBG) the predictive value of
      preoperative parameters, especially health-related quality of life (HRQoL),
      personality, psychosocial functioning, body image, and eating behavior for 2-year
      changes in these variables, as well as weight loss. RESULTS: Two years after VBG,
      patients had significant weight loss and reported improvements in physical HRQoL,
      personality and psychosocial functioning, body image, and eating behavior.
      Although we were not able to find psychosocial predictors of excess weight loss
      or excess body mass index loss 2 years after VBG, we did find psychosocial
      predictors of 2-year changes in HRQoL, personality and psychosocial functioning,
      body image, and eating behavior. CONCLUSION: Preoperative psychological
      assessment may not be necessary with respect to weight loss. However, it is
      helpful in targeting patients at risk of poor psychological outcomes after VBG.

PMID- 18317856
TI  - Comparison of volume-controlled and pressure-controlled ventilation during
      laparoscopic gastric banding in morbidly obese patients.
AB  - BACKGROUND: There are no guidelines on ventilation modes in morbidly obese
      patients. We investigated the effects of volume-controlled (VCV) and pressure
      controlled ventilation (PCV) on gas exchange, respiratory mechanics, and
      cardiovascular responses in laparoscopic gastric banding procedures. METHODS:
      After Institutional Review Board approval, 24 adult consenting patients scheduled
      for laparoscopic gastric banding were studied. Anesthesia was standardized using
      remifentanil, propofol, rocuronium, and sevoflurane. All patients started with
      VCV with a tidal volume of 10 ml kg(-1) ideal body weight, respiratory rate
      adjusted to obtain an end-tidal carbon dioxide of 35-40 mmHg, positive end
      expiratory pressure of 5 cmH2O, an inspiratory pause of 10% and an
      inspiratory/expiratory ratio of 1:2. Fifteen minutes after pneumoperitoneum, the
      patients were randomly allocated to two groups. In Group VCV (n = 12),
      ventilation was with the same parameters. In Group PCV (n = 12), the airway
      pressure was set to provide a tidal volume of 10 ml kg(-1) ideal body weight
      without exceeding 35 cm H2O. Respiratory rate was adjusted to keep an end-tidal
      carbon dioxide of 35-40 mmHg. Arterial blood samples were drawn after surgical
      positioning and 15 min after allocation. Analysis of variance (ANOVA) was used
      for statistical analysis. RESULTS: With constant minute ventilation, VCV
      generates equal airway pressures and cardiovascular effects with a lower PaCO2 as
      compared to PCV (42.5 (5.2) mmHg versus 48.9 (4.3) mmHg, p < 0.01 ANOVA).
      Arterial oxygenation remained unchanged. CONCLUSIONS: VCV and PCV appear to be an
      equally suited ventilatory technique for laparoscopic procedures in morbidly
      obese patients. Carbon dioxide elimination is more efficient when using VCV.

PMID- 18317857
TI  - Crural repair permits morbidly obese patients with not large hiatal hernia to
      choose laparoscopic adjustable banding as a bariatric surgical treatment.
AB  - BACKGROUND: Hiatal hernia, present radiologically in about 50% of patients
      desiring bariatric surgery, has been thought a contraindication to laparoscopic
      adjustable gastric banding (LAGB). Posited was the notion that adding crural
      repair to LAGB would enable this procedure to be offered to patients desiring
      bariatric surgery who had hiatal hernias. METHODS: After obtaining IRB approval,
      charts of all patients who underwent simultaneous crural repair and LAGB from
      June 2003 to January 2006 were reviewed. All patients were evaluated with the
      DeMeester score and the GERD-HQRL score pre- and postoperatively. Statistical
      analyses included the Mann-Whitney U test and the Chi-squared test. RESULTS:
      Twenty-one patients underwent laparoscopic procedure with crural repair; none
      required conversion to an open procedure. There were no mortalities. Two
      complications, a wound infection at the level of the port, and a case
      postoperative dysphagia resolved with therapy. Eighty-six percent of the patients
      ceased regular intake of heartburn medicines, P<.01. Median percent excess weight
      loss was 45% at 1 year and 55% at 2 years. The modified DeMeester score fell to 0
      2 postoperatively (P<.01). Two years after the procedure, symptoms were less, as
      assessed by GERD-HQRL scores (P<.01). CONCLUSION: Crural repair permits LAGB to
      be safely and effectively performed in patients with hiatal hernia.

PMID- 18317858
TI  - Iatrogenic injury of the intrathoracic esophagus sustained during a gastric
      banding procedure.
AB  - The wide diffusion of laparoscopic adjustable gastric banding as a common
      surgical procedure for the treatment of morbidly obese patients can be attributed
      not only to the easy surgical technique, the ability to caliber the stoma, and
      the potential for reversibility, but also to the fact that this procedure is
      associated with a low rate of immediate postoperative complications compared to
      other more complex bariatric procedures. Herein reported is the case of a 63-year
      old morbidly obese woman who sustained an iatrogenic injury of the intrathoracic
      esophagus during a laparoscopic adjustable gastric banding procedure. The
      putative mechanism of this previously unreported complication of laparoscopic
      adjustable gastric banding and the therapeutic options are discussed. The patient
      was initially treated with left pleural cavity drainage, antibiotics and the
      placement of an endoscopic silicone covered stent to cover the esophageal tear.
      Nine days later she underwent surgery through left thoracotomy due to the
      persistence of the esophageal leak. Esophageal perforation is a potentially life-
      threatening complication that may occur during a laparoscopic gastric banding
      procedure. The conservative treatment with an endoscopic stent should be reserved
      to patients with no signs of progressive systemic inflammation and include the
      drainage of the pleural cavity and the mediastinum, the endoscopic lavage and
      debridement. Standard surgical treatment with direct repair should not be
      retarded in case of persistence of the leak.

PMID- 18317859
TI  - A prospective multicenter study of 163 sleeve gastrectomies: results at 1 and 2
      years.
AB  - BACKGROUND: Good results obtained after laparoscopic sleeve gastrectomy (LSG), in
      terms of weight loss and morbidity, have been reported in few recent studies. Our
      team has designed a multicenter prospective study for the evaluation of the
      effectiveness and feasibility of this operation as a restrictive procedure.
      METHODS: From January 2003 to September 2006, 163 patients (68% women) with an
      average age of 41.57 years, were operated on with a LSG. Indications for this
      procedure were morbid obese [body mass index (BMI)>40 kg/m2] or severe obese
      patients (BMI>35 kg/m2) with severe comorbidities (diabetes, sleep apnea,
      hypertension...) with high-volume eating disorders and superobese patients
      (BMI>50 kg/m2). RESULTS: The average BMI was 45.9 kg/m2. Forty-four patients
      (26.99%) were superobese, 84 (51.53%) presented with morbid obesity, and 35
      (21.47%) were severe obese patients. Prospective evaluations of excess weight
      loss, mortality, and morbidity have been analyzed. Laparoscopy was performed in
      162 cases (99.39%). No conversion to laparotomy had to be performed. There was no
      operative mortality. Perioperative complications occurred in 12 cases (7.36%).
      The reoperation rate was 4.90% and the postoperative morbidity was 6.74% due to
      six gastric fistulas (3.66%), in which four patients (2.44%) had a previous
      laparoscopic adjustable gastric banding. Long-term morbidity was caused by
      esophageal reflux symptoms (11.80%). The percentage of loss in excessive body
      weight was 48.97% at 6 months, 59.45% at 1 year (120 patients), 62.02% at 18
      months, and 61.52% at 2 years (98 patients). No statistical difference was
      noticed in weight loss between obese and extreme obese patients. CONCLUSIONS: The
      sleeve gastrectomy seems to be a safe and effective restrictive bariatric
      procedure to treat morbid obesity in selected patients. LSG may be proposed for
      volume-eater patients or to prepare superobese patients for laparoscopic gastric
      bypass or laparoscopic duodenal switch. However, weight regained, quality of
      life, and evolution ofmorbidities due to obesity need to be evaluated in a long
      term follow up.

PMID- 18317860
TI  - Latin American Chapter of the International Federation for the Surgery of Obesity
      (IFSO-LA).

PMID- 18317861
TI  - Late results of absorbable pin fixation in the treatment of radial head
      fractures.
AB  - The use of bioabsorbable pins with prolonged degradation periods for fracture
      fixation has raised concerns about adverse soft tissue reactions, including
      seromas, discharging sinuses, or osteolytic changes. We asked whether
      bioabsorbable pins of self-reinforced polylactic acid polymer used in radial head
      fractures resulted in such reactions. We retrospectively reviewed 21 patients
      followed a minimum of 36 months (mean, 81 months; range, 36-136 months). There
      were nine Mason II, 10 Mason III, and two Mason IV fractures, which were
      evaluated clinically and radiographically. All fractures healed well with no
      radiographic signs of osteolysis. The mean Mayo Elbow Performance score was 93.8
      (range, 20-100), which is comparable to the outcome of historical groups with
      radial head arthroplasty. The mean range of flexion of the elbow was 9 degrees to
      132 degrees , with 79 degrees pronation and 77 degrees supination. The grip
      strength of the operated arm was not affected in comparison to the contralateral
      arm (mean range, 38.6 versus 40.9 kg). No material-related adverse effects were
      observed during and beyond the degradation period. Our data suggest concerns
      about soft tissue or bony reactions from these materials in radial head fractures
      are not justified.

PMID- 18317863
TI  - A cost-effective mesh design for extraperitoneal inguinal hernia repair using
      lightweight mesh.

PMID- 18317862
TI  - The effect of the microscopic and nanoscale structure on bone fragility.
AB  - Bone mineral density is the gold-standard for assessing bone quantity and
      diagnosing osteoporosis. Although bone mineral density measurements assess the
      quantity of bone, the quality of the tissue is an important predictor of
      fragility. Understanding the macro- and nanoscale properties of bone is critical
      to understanding bone fragility in osteoporosis. Osteoporosis is a disease that
      affects more than 75 million people worldwide. The gold standard for osteoporosis
      prognosis, bone mineral density, primarily measures the quantity of bone in the
      skeleton, overlooking more subtle aspects of bone's properties. Bone quality, a
      measure of bone's architecture, geometry and material properties, is evaluated
      via mechanical, structural and chemical testing. Although decreased BMD indicates
      tissue fragility at the clinical level, changes in the substructure of bone can
      help indicate how bone quality is altered in osteoporosis. Additionally,
      mechanical properties which can quantify fragility, or bone's inability to resist
      fracture, can be changed due to alterations in bone architecture and composition.
      Recent studies have focused on examination of bone on the nanoscale, suggesting
      the importance of understanding the interactions of the mineral crystals and
      collagen fibrils and how they can alter bone quality. It is therefore important
      to understand alterations in bone that occur at the macro-, micro- and nanoscopic
      levels to determine what parameters contribute to decreased bone quality in
      diseased tissue.

PMID- 18317864
TI  - Not only headache: higher degree of sexual pain symptoms among migraine
      sufferers.
AB  - Chronic illness and chronic pain can have profound negative effects on
      relationship and sexual satisfaction, yet the influence of migraine on sexuality
      has not been previously evaluated. To assess sexual functions in subjects with
      migraine compared to those with no migraine. We evaluated female university
      students using the Israeli sexual behavior inventory (ISBI). Migraine was
      diagnosed according to self-reported symptoms according to the IHS criteria.
      Several dimensions of female sexuality--desire, orgasm, sexual avoidance,
      interpersonal sexual relationship, health influence, satisfaction and pain were
      evaluated using a structured questionnaire. Thirty-three (23.9%) of the
      participants met the IHS criteria for episodic migraine with and without aura.
      Sexual activity, desire, orgasm and satisfaction from sexual life did not differ
      significantly between migraine sufferers and non-sufferers. Migraine patients
      reported lower ISBI scores, higher health influence on sexual life, higher levels
      of sexual pain and lower sexual satisfaction. Migraine negatively affected the
      sexual life of sufferers. Sexual pain disorder is more common among migraine
      sufferers compared to non-migraineurs.

PMID- 18317865
TI  - Triptans in the Italian population: a drug utilization study and a literature
      review.
AB  - Previous studies performed in selected populations show a poor utilization of
      triptans for migraine. The objectives of our study were to establish patterns of
      triptans utilization in a large sample, covering 1/10 of Italian population (5.57
      millions), and to perform a review of published studies on this topic. We
      investigated drug prescription database collected during 2006 from 33 health
      authorities distributed in 8 different regions. About 0.6% of the subjects
      received at least one prescription of triptans in 1 year: 77.7% were females and
      22.3% males. Age distribution shows that 9.5% of patients were aged above 65, and
      received prescriptions for 8.2% of packages. The review of the literature
      suggests that these percentages of utilization are common to several countries,
      and shows that occasional triptan users who received only one prescription in 1
      year are a large percentage (40-60%); moreover, a minor population of triptan
      users utilize a large amount of total triptans. Finally triptans are frequently
      prescribed in people aged above 65 years, a population in which triptans are
      contraindicated or not recommended. Our study and the analyzed ones indicate
      suboptimal treatment of migraine patients with triptans and also an incorrect use
      in some patients (triptan abusers, elderly).

PMID- 18317866
TI  - Rimonabant for overweight and "metabolic syndrome": the attempt to supersize
      disease and risk by pharmaceutical marketing.

PMID- 18317867
TI  - A case of adult croup.

PMID- 18317868
TI  - Risk factors for upper limb deep vein thrombosis associated with the use of
      central vein catheter in cancer patients.
AB  - Deep vein thrombosis of upper limb is a common complication of CVC in patients
      with cancer. In these patients the risk factors for CVC-related thrombosis are
      not completely defined. The purpose of this study was to identify the risk
      factors for CVC-related thrombosis in patients included in a randomized, double
      blind, placebo-controlled study aimed at assessing the efficacy and safety of
      enoxaparin for the prophylaxis of CVC-related thrombosis. CVC-related thrombosis
      was screened by mandatory venography after 6 weeks of study treatment. A number
      of patient baseline characteristics were assessed as potential risk factors for
      CVC-related deep vein thrombosis. Crude associations between risk factors and
      clinical outcomes were assessed by chi(2) test or Fisher's exact test. Multiple
      logistic regression analysis was used to identify independent risk factors. A CVC
      related thrombosis was found in 50 out of 310 patients (16.1%). At multiple
      logistic regression analysis, CVC tip misplaced in the upper half of superior
      vena cava (OR 4.05, 95%CI 1.64-10.02), left-sided CVC insertion (OR 2.29, 95%CI
      1.01-5.51) and chest radiotherapy (OR 7.01, 95%CI 1.42-34.66) were independent
      risk factors for thrombosis. In addition to these risk factors, the presence of
      distant metastases (OR 9.36, 95%CI 1.53-57.05) increased the risk of thrombosis
      in patients who received placebo. An inadequate position of the CVC tip, left
      sided CVC insertion and chest radiotherapy are independent risk factors for CVC
      related thrombosis in cancer patients. Patients with distant metastases have an
      increased risk for thrombosis in absence of antithrombotic prophylaxis.

PMID- 18317869
TI  - Two-phase surgical treatment of anteromedial knee injuries.
AB  - The treatment of severe anteromedial knee injuries over the years has undergone
      various types of approach, changing from proposals, such as combined surgical
      repair of the anterior cruciate ligament and medial compartment, to the more
      current protocol which involves conservative treatment of the peripheral injury
      and later reconstruction of the anterior cruciate ligament. However, in serious
      ruptures of the medial ligament compartment, conservative treatment does not make
      it possible to recover peripheral stability, thus transferring abnormal forces
      onto the anterior cruciate pro-ligament graft which can gradually deteriorate the
      transplant itself. Thus in severe anteromedial injuries a treatment with two
      distinct surgical phases is proposed, using direct immediate suture of the
      peripheral compartment and, after a period of rehabilitation, later replacement
      of the anterior cruciate ligament by arthroscope graft. Given the obtained
      results and the few complications observed in 25 cases, it is probable that this
      therapeutic scheme can be proposed in selected cases of severe ligament laxity of
      the medial compartment associated with rupture of the anterior cruciate ligament.

PMID- 18317870
TI  - Norovirus infection among children with acute gastroenteritis in Recife, Brazil:
      disease severity is comparable to rotavirus gastroenteritis.
AB  - Norovirus has captured increasing attention as an agent of childhood diarrhoea.
      However, it is not known whether norovirus causes as severe diarrhoea as
      rotavirus, particularly among children in developing countries. In a 1-year study
      conducted between May 2004 and April 2005 in Recife, Brazil, norovirus was
      detected by ELISA in 34/233 (15%) diarrhoeal children less than 5 years of age.
      The severity of clinical illness, as indicated by the presence of dehydration,
      the requirement for hospitalization, and the duration of hospital stay, was
      similar between children with norovirus and rotavirus infection. These data
      underscore the importance of norovirus as a cause of severe diarrhoea in
      children.

PMID- 18317871
TI  - Synthesis, spectroscopic and structural elucidation of tyrosinamide
      hydrogensquarate monohydrate.
AB  - Synthesis, isolation, spectroscopic and structural elucidation of tyrosinamide
      hydrogensquarate monohydrate (I) is reported on the basis of quantum chemical DFT
      calculations, vibrational analysis and experimental linear-polarized IR
      spectroscopy in solid state. These data are compared with those obtained using
      single crystal X-ray diffraction, which show that the molecules of (I) in the
      unit cell formed 3D network through moderate intermolecular (Tyr)OH...O = C(Sq)
      (2.727 A), O=C-NH2...OH(Tyr) (2.991 A), O=C-NH2...OH(Sq) (2.988 A), O=C-NH2...O=C
      NH2 (3.068 A), N+H3...O=C(Sq) (2.737, 2.953, 2.954 A), OH2...O=C(Sq) (2.839 A)
      and (Sq)OH...OH2 (2.607 A) hydrogen bonds. The relationship between the structure
      and spectroscopic properties is studied.

PMID- 18317872
TI  - Synthesis, spectroscopic and structural elucidation of sympathomimetic amine,
      tyraminium dihydrogenphosphate.
AB  - The synthesis, isolation, spectroscopic and structural elucidation of
      sympathomimetic amine, tyramine dihydrogenphosphate are of interest due to its
      biological activity and the establishing correlation between spectroscopic
      properties and structure. The complex approach for investigation included single
      crystal X-ray diffraction, new technique in linear-polarized IR-spectroscopy in
      solid state and quantum chemical calculations with a view to predict the
      electronic structure and vibrational data of interacting species in entitled
      compound, the correlation structure-spectroscopic properties as well as the
      influence of intermolecular interaction on IR-characteristic bands are carried
      out.

PMID- 18317873
TI  - Statistical analysis of the associations between polymorphisms within aldehyde
      dehydrogenase 2 (ALDH2), and quantitative and qualitative traits extracted from a
      large-scale database of Japanese single-nucleotide polymorphisms (SNPs).
AB  - A scan of 4,190 single-nucleotide polymorphisms (SNPs) in 199 different genes
      using 38 different quantitative traits to search for associations between
      genotypes and phenotypes detected an association between the genotypes at rs671
      of ALDH2 and gamma-glutamyltranspeptidase (gamma-GTP) levels. We examined the
      associations between five factors such as gender, age, rs671 genotype, alcohol
      drinking habit, and serum gamma-GTP level and found that all pairs were
      associated except for the pair of rs671 genotype and gender and rs671 genotype
      and age. We further analyzed the data by both multiple regression and subgroup
      analyses and found that the associations between rs671 genotype and alcohol
      drinking habit, alcohol-drinking habit and gamma-GTP level, gender and gamma-GTP,
      and age and gamma-GTP were independent of other factors. Conversely, the
      association between rs671 genotype and gamma-GTP level was dependent on alcohol
      drinking habit. Associations between genetic and environmental factors will
      become a focus of medical and biological studies. Our study has shown that (1) a
      large sample size combined with a replication study is necessary to overcome the
      multiple-comparison problem, and (2) subgroup analysis along with logistic and
      linear multiple regression analysis may be useful to dissect a complicated
      relationship.

PMID- 18317874
TI  - Serum levels of cystatin C in patients with malignancy.
AB  - BACKGROUND: Serum levels of cystatin C have been proposed to be an ideal marker
      of the glomerular filtration rate (GFR). However, some reports have shown that
      serum levels of cystatin C increase independently of GFR. In this study, we
      evaluated the clinical utility of cystatin C in monitoring GFR, especially in
      patients with a malignancy. METHOD: Study subjects consisted of 82 patients with
      a malignancy, 39 patients with a non-malignancy, 31 healthy volunteers, and 206
      patients with various degrees of renal function. We measured serum cystatin C,
      beta2-microglobulin (beta 2mG), and creatinine (CRE) levels in all patients.
      Serum CRP levels were measured in 21 patients with a malignancy and 28 patients
      with a non-malignancy whose creatinine clearance (Ccr) was > or =70 ml/min.
      Cystatin C, beta 2mG, and CRP were measured by immune nephelometry and CRE was
      measured by an enzyme assay. RESULTS: In patients with a malignancy, regression
      analysis yielded the equation: 1/cystatin C = 0.06 x Ccr + 0.710, correlation
      coefficient, r, of 0.33. The r was significantly lower than in patients with
      various degrees of renal function. There were no significant differences when the
      r performed on beta 2mG and CRE was compared between the same groups of patients.
      In 74 patients with a malignancy, in whom serum CRE levels were < or =1.1 mg/dl,
      increased levels of cystatin C were observed in 25 patients and increased levels
      of beta 2mG were observed in 39 patients. In comparing patients with a malignancy
      and a non-malignancy, the number of patients with an increased level of cystatin
      C, despite a Ccr > or = 70 ml/min (8/33) or a CRE < or = 1.1 mg/dl (13/41), was
      larger in the former group than the latter group, although the result was not
      statistically significant. Similarly, the number of patients with an increased
      level of beta 2mG, despite a Ccr > or = 70 ml/min or a CRE < or = 1.1 mg/dl was
      significantly larger in the former group compared to the latter group. Regression
      analysis between the serum levels of cystatin C and CRP in patients with a
      malignancy whose Ccr were > or =70 ml/min had a weak correlation (r = 0.31).
      CONCLUSION: The results of our study suggest that the serum levels of cystatin C
      are not always a reliable marker of the GFR in patients with a malignancy,
      probably in relation to its nature as a cysteine protease inhibitor.

PMID- 18317875
TI  - Renoprotective effects of angiotensin II receptor blocker, candesartan cilexetil,
      in patients with stage 4-5 chronic kidney disease.
AB  - BACKGROUND: To investigate the renoprotective effects and safety of angiotensin
      II receptor blocker (ARB) for patients with stage 4-5 chronic kidney disease.
      METHODS: An ARB, candesartan cilexetil, was administered to 13 patients (ARB
      group, n = 7; control group, n = 6) with a serum creatinine level of 2.52-5.95
      mg/dl whose blood pressure had been maintained below 140/90 mmHg by the use of
      drugs other than ARBs. Routine measurements were conducted for 48 weeks, and
      renal survival analysis was observed for up to 3 years with the endpoints being
      doubling of the serum creatinine level, entry to hemodialysis, or death. The
      results were compared with those of the control group that was not treated with
      ARB. RESULTS: No significant changes were observed in the blood pressure in
      either group. Proteinuria significantly decreased from 0.95 +/- 0.51 to 0.39 +/-
      0.12 g/day (paired t test, P = 0.033) in the ARB group, but did not change in the
      control group. Creatinine clearance in the control group decreased significantly
      from 16.2 +/- 5.7 to 10.4 +/- 4.8 ml/min per 1.73 m2 (paired t test, P = 0.011),
      but did not change in the other group. Thus, the slopes of the reciprocal serum
      creatinine values became less steep in the ARB group as compared with the control
      (-0.002 +/- 0.015 vs. -0.025 +/- 0.015 dl/mg per month; unpaired t test, P =
      0.019). Kaplan-Meier analysis revealed that ARB exhibited more favorable renal
      outcome at 3 years (log-rank, P = 0.025). No serious adverse events were noted in
      the study. CONCLUSION: These results show that ARB reduces proteinuria and
      protects renal function even in the advanced renal failure.

PMID- 18317876
TI  - Aldosterone and glomerular podocyte injury.
AB  - Aldosterone is traditionally viewed as a hormone regulating electrolyte and blood
      pressure homeostasis by acting on the distal nephron. Accumulating evidence
      suggests that aldosterone also plays pathogenetic roles in cardiovascular and
      renal injury. For example, aldosterone is a potent inducer of proteinuria. We
      demonstrated that podocyte injury underlies the pathogenesis of proteinuria in
      aldosterone-infused rats on a high salt diet. Mineralocorticoid receptor was
      detected in the podocytes in vivo and in vitro, and aldosterone caused induction
      of its effector kinase Sgk1, activation of NADPH oxidase and generation of
      reactive oxygen species. Selective aldosterone blocker eplerenone, as well as
      antioxidant tempol, ameliorated aldosterone-induced podocyte injury and
      proteinuria. Aldosterone was also involved in the podocyte damage and proteinuria
      of metabolic syndrome model SHR/NDmcr-cp. Adipocyte-derived aldosterone releasing
      factors were suggested to contribute to the aldosterone excess of this model.
      Furthermore, high salt diet markedly worsened the renal injury of SHR/NDmcr-cp.
      Although salt lowered serum aldosterone levels, it caused MR activation in the
      kidney. Accordingly, eplerenone dramatically improved the salt-evoked
      nephropathy. Taken together, aldosterone blockers can be an excellent therapeutic
      strategy for the treatment of podocyte injury, proteinuria, and cardiovascular
      and renal complications, not only in high aldosterone states but also in patients
      with activated MR signaling in the target tissue, whose circulating aldosterone
      level is not necessarily high. Addition of aldosterone blockers in patients
      treated with ACEIs or ARBs are also promising, because of "aldosterone
      breakthrough" phenomenon. Careful monitoring of hyperkalemia is necessary,
      especially in patients with impaired renal function.

PMID- 18317877
TI  - Maximum intensity projection as a tool to diagnose early rheumatoid arthritis.
AB  - In this study, we investigated the usefulness of contrast-enhanced MRI with
      maximum intensity projection (MIP) as a convenient tool for detecting early
      rheumatoid arthritis (RA). A total of 21 patients with undiagnosed arthritis of
      the hands at the initial visit were enrolled in a prospective study over a 1-year
      period. The number of swollen joints found during physical examination at this
      first visit, the results of serological tests and the number of synovitis joints
      diagnosed on MIP images were compared between the RA group and non-RA group. Of
      the 21 patients, 17 (81%) from the initial study who were followed up for an
      additional 1 year entered this study. Of these, 5 met the conditions for
      diagnosis of RA during follow-up, and 12 did not. MIP images were used to review
      the arthritis of RA patients, and a significant difference was found in the
      number of synovitis inflammations detected with MIP images when compared with
      findings after physical examinations. The two criteria of positive CARF and/or
      anti-CCP antibody and symmetrical synovitis in bilateral hands on MIP images
      allowed the prediction of RA with 100% sensitivity and 75% specificity. Thus, MIP
      is a useful tool for making early diagnosis of RA because it yields clear
      visualization even with just one image.

PMID- 18317878
TI  - Hughes syndrome (the antiphospholipid syndrome): 25 years old.
AB  - The antiphospholipid (Hughes) syndrome (APS) is a unique thrombotic disorder,
      causing both arterial and venous thrombosis, linked to the presence of antibodies
      directed against phospholipid-protein complexes. The first papers describing the
      syndrome were published in 1983 and, over the next two years, a series of
      publications described in detail the various clinical manifestations of the
      syndrome. Laboratory standardisation workshops were also set up and, in 1984, the
      first "world" symposium on APS was held. The international APS conferences have
      continued to grow in numbers and in stature. The APS has already had an impact in
      obstetrics, in medicine, in psychiatry, and in surgery. The approximate figure of
      1 in 5 is a useful guide -- 1 in 5 of all young strokes, 1 in 5 recurrent
      miscarriages, 1 in 5 DVTs. More precise data will become available in the worlds
      of epilepsy, migraine, Alzheimer's, and MS. The advent of newer "biologic"
      immunosuppressives such as rituximab may offer help in selected cases.
      Intravenous immunoglobulin has proved successful, especially in the emergency
      setting.

PMID- 18317879
TI  - Life expectancies of Japanese patients with rheumatoid arthritis: a review of
      deaths over a 20-year period.
AB  - We investigated trends in life expectancy in rheumatoid arthritis (RA) patients,
      reviewing records for 286 patients (204 female, 82 male) who had died over the
      past 20 years. The average age at death was 68.8 years before 1990, increasing to
      72.1 years after 2001. Trends in disease modifying anti-rheumatic drugs (DMARDs)
      saw gold preparations (45.2%) predominate before 1990, sulphydryl donor agents
      (53.6%) from 1991 to 2000, then methotrexate (43.0%) after 2001. The most common
      causes of death were infectious diseases up to 1995, rheumatic disease 1996-2000,
      and cardiovascular events and malignancies after 2001. Major advances in surgical
      interventions, such as joint replacement surgery, occurred after 1990. Surgical
      intervention followed by a period of rehabilitation maintained a favourable level
      of activities of daily living (ADLs), The requirements for favourable life
      expectancy are control of RA inflammation and maintenance of a favourable level
      of ADLs. Although recently developed DMARDs and biological agents show promise,
      caution is required to avoid serious adverse reactions. Optimum care of patients
      with RA will require preventive measures and early intervention for infections
      and rheumatic diseases, as well as for lifestyle diseases, osteoporosis and
      malignancies.

PMID- 18317880
TI  - Differential expression of HOX genes upon activation of leukocyte sub
      populations.
AB  - The HOX genes are key determinants of cellular identity both in early development
      and in the renewal and differentiation of adult blood cells. Although a number of
      studies have examined the expression of individual HOX genes in defined blood
      cell lineages, we have undertaken a comprehensive analysis of HOX gene expression
      in resting and activated lymphocytic and monocytic subpopulations. This has
      revealed distinct patterns of expression between different cell types and resting
      and activated states. (Main category A: Erythrocytes, Leukocytes and
      Hematopoiesis, subcategory: 8: Lymphocytes).

PMID- 18317881
TI  - Successful autologous peripheral blood stem cell transplantation in a Jehovah's
      Witness with multiple myeloma: review of literature and recommendations for high
      dose chemotherapy without support of allogeneic blood products.
AB  - We present a case report of a successful high-dose melphalan therapy and
      autologous stem cell transplantation without the use of allogeneic blood product
      support in a 70-year-old patient suffering from multiple myeloma. Based on the
      experience in this case and thorough evaluation of the literature, we consider
      pre-transplant Hb level of 11-12 g/dl, platelet count higher than 70/nl, good WHO
      performance status of two and lower and informed consent as important eligibility
      criteria. During cytopenia recommended supportive measures include growth factor
      support with erythropoietin and G-CSF, p.o. iron treatment as well as
      prophylactic use of anti-fibrinloytic agents. Furthermore we discuss additional
      options that might be considered depending on the individual factors as e.g. pre
      transplant collection and cryoconservation of autologous platelet concentrates.
      Moreover, an analysis of socio-economic issues regarding this procedure is
      presented. We conclude that allogeneic blood product free transplantation is a
      feasible procedure that can be offered to the patients belonging to distinct
      religious groups refusing allogeneic blood products as Jehovas Witnesses and
      patients presenting other contraindications for transfusions.

PMID- 18317882
TI  - Virus reactivation in high-risk non-Hodgkin's lymphoma patients after autologous
      CD34+ -selected peripheral blood progenitor cell transplantation.
AB  - CD34+-selected peripheral blood progenitor cells (PBPCs) may not only reduce
      contaminated tumor cells but also compromise immunologic reconstitution and
      increase incidence of infections after transplantation. We analyzed the incidence
      of virus reactivation in CD34+-selected PBPCs autologous transplantation. From
      December 2001 to December 2004, ten high-risk aggressive non-Hodgkin's lymphoma
      (NHL) patients were enrolled in a program of high-dose chemotherapy plus
      autologous CD34+-selected PBPCs support. Viral screening studies, including
      clinical symptoms, physical examinations, hepatitis B virus (HBV)-DNA,
      cytomegalovirus (CMV)-polymerase chain reaction (PCR), rapid diagnosis of
      fluorescent antibody stain for herpes-simplex virus (HSV), and viral culture from
      blood, fluid or tissue were performed weekly during the first 3 months and then
      monthly for 1 year. Two of four patients (50%) who were HBV carriers developed
      HBV reactivation. The other two HBV carriers who received prophylactic lamivudine
      therapy did not develop HBV reactivation. Two patients (20%) developed
      cytomegalovirus (CMV) infection, and three patients (30%) developed HSV infection
      in total ten serum-positive patients. The possibility of virus reactivation might
      increase in NHL patients undergoing autologous CD34+-selected PBPC
      transplantation. Administering prophylactic antivirus therapy and closely
      following patient's clinical viral complications should be considered.

PMID- 18317883
TI  - Identification of genes potentially involved in supporting hematopoietic stem
      cell activity of stromal cell line MC3T3-G2/PA6.
AB  - Although coculture of hematopoietic stem cells (HSCs) with stromal cells is a
      useful system to study hematopoiesis in the niche, little is known regarding the
      precise cellular and molecular mechanisms of maintaining HSCs through cell-cell
      interactions. The murine preadipose stromal cell line MC3T3-G2/PA6 (PA6) has been
      demonstrated to support HSCs in vitro. In this study, microarray analysis was
      performed on PA6 cells and HSC-nonsupporting PA6 subclone cells to identify genes
      responsible for supporting HSC activity. Comparison of gene expression profiles
      revealed that only 144 genes were down-regulated by more than twofold in PA6
      subclone cells. Of these down-regulated genes, we selected 11 candidate genes and
      evaluated for the maintenance of HSC function by overexpressing these genes in
      PA6 subclone cells. One unknown gene, 1110007F12Rik (also named as Tmem140),
      which is predicted to encode an integral membrane protein, demonstrated a partial
      restoration of the defect in HSC-supporting activity.

PMID- 18317884
TI  - In vivo single molecular imaging and sentinel node navigation by nanotechnology
      for molecular targeting drug-delivery systems and tailor-made medicine.
AB  - The recent advances in nanotechnology have a great potential to improve the
      prevention, diagnosis, and treatment of human diseases. Nanomaterials for medical
      applications are expected to grasp pharmacokinetics and the toxicity for
      application to medical treatment on the aspect of safety of the nanomaterials and
      nanodevices. We describe a generation of CdSe nanoparticles [quantum dots (QDs)]
      conjugated with monoclonal anti-HER2 antibody (Trastuzumab), for single molecular
      in vivo imaging of breast cancer cells. We established a high-resolution in vivo
      3D microscopic system for a novel imaging method at the molecular level. The
      cancer cells expressing HER2 protein were visualized by the nanoparticles in vivo
      at subcellular resolution, suggesting future utilization of the system in medical
      applications to improve drug-delivery systems to target the primary and
      metastatic tumors for made-to-order treatment. We also describe sentinel node
      navigation using fluorescent nanoparticles for breast cancer surgery in
      experimental model, which have shown the potential to be an alternative to
      existing tracers in the detection of the sentinel node if we select the
      appropriate particle size and wavelength. Future innovation in cancer imaging by
      nanotechnology and novel measurement technology will provide great improvement,
      not only in the clinical field but also in basic medical science for the
      development of medicine.

PMID- 18317885
TI  - Bilateral breast MR imaging: is it superior to conventional methods for the
      detection of contralateral breast cancer?
AB  - BACKGROUND: Breast MR imaging has emerged as a highly sensitive modality for the
      imaging of breast tumors. However, there have been no reports concerning the
      usefulness of bilateral breast MRI to evaluate the contralateral breast in Japan.
      The purpose of this study was to examine the frequency of primary bilateral
      breast cancer, and to investigate the role of bilateral breast MRI in the
      detection of contralateral breast cancer. METHODS: A retrospective review was
      performed of 556 consecutive women who had undergone surgery for the primary
      breast cancer. MR imaging was performed on a 1.5-T system. Both the breasts were
      examined in the coronal plane on the first-, second-, and fourth-phase dynamic
      images, acquired at 30, 90 s, and 4.5 min, respectively. The affected single
      breast was sagittally examined on images obtained in the third phase at 3 min.
      RESULTS: Twenty-four (4.3%) patients had bilateral breast cancer, 14 (2.5%) had
      synchronous cancer and 10 patients (1.8%) had metachronous cancer. In the 14
      cases with synchronous cancer, bilateral breast malignancy was suspected at the
      time of the initial diagnosis in 6 cases. The detection rate of 18 contralateral
      breast cancer cases by only MMG, only US, MMG and US, and MRI were 50% (9/18),
      67% (12/18), 78% (14/18) and 100% (17/17), respectively. For 8 of these cases
      with a second synchronous cancer, the corresponding rates were 75, 88, 100 and
      100%, respectively. For the 10 cases with a second metachronous cancer, the rates
      were 30, 50, 60 and 100%, respectively. CONCLUSION: Bilateral breast MRI is a
      more sensitive for the detection of contralateral breast cancers compared with
      conventional imaging methods. In particular, bilateral MRI also allows detection
      of metachronous contralateral cancers at an earlier stage during the
      postoperative follow-up period.

PMID- 18317886
TI  - Plasmid CpG depletion improves degree and duration of tumor gene expression after
      intravenous administration of polyplexes.
AB  - PURPOSE: Tumor gene expression after the intravenous (i.v.) administration of
      current polymer-based gene delivery systems is generally low and short-lived.
      Immune stimulatory CpG dinucleotides, present within the plasmid DNA of the
      polyplexes are likely to contribute to this. The effect of CpG replacement on the
      levels of transgene expression was studied, after the i.v. administration of
      polyethylenimine (PEI) polyplexes. METHODS: Tumor transfection and immune
      stimulation of PEI polyplexes containing plasmid DNA encoding for luciferase and
      rich in CpG motifs was monitored and compared to polyplexes containing the same
      gene but devoid of CpG motifs. Lipoplexes based on 1,2-dioleyl-3
      trimethylammonium-propane/dioleoylphosphatidylethanolamine liposomes were
      included as a control. RESULTS: The replacement of CpGrich DNA by CpGfree DNA did
      neither affect the physical properties of the DNA complexes nor did it affect
      their in vitro transfection activity or cytotoxicity. The immune stimulation
      (interleukin-12) after i.v. administration of the PEI DNA complexes was low and
      unaffected by the presence of CpG motifs. The absence of CpG motifs within the
      different DNA complexes improved the degree and the duration of organ and tumor
      gene expression. CONCLUSION: The depletion of CpG dinucleotides within the
      plasmid DNA of polyplexes enhances the degree and duration of in vivo transgene
      expression.

PMID- 18317887
TI  - Suppression of NFkappaB and its regulated gene products by oral administration of
      green tea polyphenols in an autochthonous mouse prostate cancer model.
AB  - PURPOSE: This study examines the role of cell survival/apoptosis related proteins
      involved in NFkappaB signaling pathways and its associated events in GTP-induced
      chemoprevention of prostate cancer in TRAMP mice. METHODS: Mice were given 0.1%
      GTP as drinking fluid. Western blot and immunohistochemical analysis performed to
      examine NFkappaB and its regulated pathway in response to GTP. RESULTS: Our data
      demonstrated increased expression of NFkappaB, IKKalpha, IKKbeta, RANK, NIK and
      STAT-3 in dorso-lateral prostate of TRAMP mice as a function of age and tumor
      growth and continuous GTP infusion for 32 weeks resulted in substantial reduction
      in these proteins. The levels of transcription factor osteopontin, a non
      collagenous extracellular matrix protein, were also downregulated. Inhibition of
      NFkappaB signaling is known to activate apoptotic and inhibit anti-apoptotic
      proteins. Therefore, we analyzed Bax and Bcl2 levels in the dorsolateral prostate
      of TRAMP mice fed GTP and observed a shift in balance between Bax and Bcl2
      favoring apoptosis. CONCLUSIONS: Based on the data we suggest that oral
      consumption of GTP might inhibit osteopontin and NFkappaB signaling that may
      contribute to induction of apoptosis observed in GTP fed TRAMP mice.

PMID- 18317888
TI  - Replication of low-risk gambling limits using canadian provincial gambling
      prevalence data.
AB  - A set of low-risk gambling limits were recently produced using Canadian
      epidemiological data on the intensity of gambling behavior and related
      consequences (Currie et al. Addiction 101:570-580, 2006). The empirically derived
      limits (gambling no more than two to three times per month, spending no more than
      $501-$100o CAN per year or no more than 1% of gross income spent on gambling)
      accurately predicted risk of gambling-related harm after controlling for other
      risk factors. The present study sought to replicate these limits on data
      collected in three independently conducted Canadian provincial gambling surveys.
      Dose-response curves and logistic regression analyses were applied to gambling
      prevalence data collected in surveys conducted in 2001-2002 within the provinces
      of Alberta, British Columbia, and Ontario (combined sample N = 7,675). A
      comparable dose-response relationship between gambling intensity and risk of harm
      was found in each province. The optimal thresholds for defining an upper limit of
      low-risk gambling were similar across the three provinces despite variations in
      the availability and organization of legalized gambling opportunities within each
      region. These results provide additional evidence supporting the validity of the
      low-risk gambling limits. Quantitative limits could be used to augment existing
      responsible gambling guidelines.

PMID- 18317889
TI  - Kinetics of ethanol oxidation catalyzed by yeast alcohol dehydrogenase in aqueous
      solutions of sodium dodecylsulfate.
AB  - A study has been made of the effect of sodium dodecylsufate (SDS) addition on the
      oxidation of ethanol catalyzed by yeast alcohol dehydrogenase. Experiments were
      performed at pH = 8.1 and SDS concentrations employed were below and above the
      surfactant critical micelle concentration (CMC). The double reciprocal plots
      obtained in the absence and in the presence of the surfactant were compatible
      with a sequential bi-bi ordered mechanism. In the presence of the surfactant the
      initial reaction rates were consistently lower than in pure buffer at all the
      surfactant concentrations considered (0.5-50 mM). This effect is mainly due to an
      increase in the dissociation constant of beta-NAD(+) which reaches its maximum
      value (7,100 +/- 1,700 microM) at the CMC. Above the CMC the effect of the
      surfactant is mainly due to an increase in the Michaels constants of the alcohol,
      with values of 41 +/- 1 mM for 15 mM SDS and 50 +/- 1 mM for 50 mM SDS. The
      catalytic rate constant was found to be practically independent of the presence
      of the surfactant in the range of concentrations considered (up to 50 mM).

PMID- 18317890
TI  - Spanish translations of Miranda warnings and the totality of the circumstances.
AB  - Spanish-translated Miranda warnings are administered annually to thousands of
      Hispanic custodial suspects. In examining 121 Spanish translations and their
      English counterparts from 33 states, the lengths of Miranda warnings were
      generally comparable but marked differences were observed in the reading levels
      for individual Miranda components. The adequacy of Miranda translations varies
      markedly from minor variations to substantive errors. The most serious problems
      involved the entire omission of Miranda components; several omissions were
      observed in the Spanish translations for even the basic rights to silence and
      counsel. More commonly, Miranda discrepancies involved dissimilar content with a
      substantial trend toward more information in English than Spanish versions.
      Findings related to the Miranda translations, different word lengths, and varied
      reading levels are discussed using the totality of circumstances as its
      framework.

PMID- 18317891
TI  - Racial disparities in perinatal outcomes and pregnancy spacing among women
      delaying initiation of childbearing.
AB  - INTRODUCTION: Reducing racial/ethnic disparities is a key objective of the
      Healthy People 2010 initiative. Unfortunately, racial disparities among women
      delaying initiation of childbearing have received limited attention. As more
      women in the US are delaying initiation of childbearing, it is important to
      examine racial disparities in reproductive health outcomes for this subgroup of
      women. OBJECTIVE: To examine racial disparities in perinatal outcomes,
      interpregnancy interval, and to assess the risk for adverse outcomes in
      subsequent pregnancy for women delaying initiation of childbearing until age 30
      or older compared to those initiating childbearing at age 20-29. METHODS: We
      conducted a retrospective cohort study using the Missouri maternally linked
      cohort files 1978-1997. Final study sample included 239,930 singleton sibling
      pairs (Whites and African Americans). Outcome variables included first and second
      pregnancy outcomes (fetal death, low birth weight, preterm delivery and small-for
      gestational age) and interpregnancy interval between first and second pregnancy.
      Independent variables included maternal age at first pregnancy and race. Analysis
      strategies used involved stratified analyses and multivariable unconditional
      logistic regression; interactions between maternal race, age and interpregnancy
      interval were examined in the regression models. RESULTS: Compared to Whites,
      African American mothers initiating childbearing at age 30 or older had
      significantly higher rates of adverse outcomes in the first and second pregnancy
      (P < 0.0001). Generally, African Americans had significantly higher rates of
      second pregnancy following intervals <6 months compared to Whites; however, no
      significant racial differences were noted in interpregnancy interval distribution
      pattern after controlling for maternal age at first pregnancy. African Americans
      delaying initiation of childbearing had significantly higher risk for adverse
      perinatal outcomes in the second pregnancy compared to Whites after controlling
      for potential confounders, however there were no significant interactions between
      maternal age at first pregnancy, race and short interpregnancy interval.
      CONCLUSION: Although African Americans were less likely to delay initiation of
      childbearing than were White women, their risk for adverse perinatal outcomes was
      much greater. As health care providers strive to address racial disparities in
      birth outcomes, there is need to pay attention to this unique group of women as
      their population continues to increase.

PMID- 18317892
TI  - Food security during infancy: implications for attachment and mental proficiency
      in toddlerhood.
AB  - OBJECTIVE: This study examined the associations between household food security
      (access to sufficient, safe, and nutritious food) during infancy and attachment
      and mental proficiency in toddlerhood. METHODS: Data from a longitudinal
      nationally representative sample of infants and toddlers (n = 8944) from the
      Early Childhood Longitudinal Study-9-month (2001-2002) and 24-month (2003-2004)
      surveys were used. Structural equation modeling was used to examine the direct
      and indirect associations between food insecurity at 9 months, and attachment and
      mental proficiency at 24 months. RESULTS: Food insecurity worked indirectly
      through depression and parenting practices to influence security of attachment
      and mental proficiency in toddlerhood. CONCLUSIONS: Social policies that address
      the adequacy and predictability of food supplies in families with infants have
      the potential to affect parental depression and parenting behavior, and thereby
      attachment and cognitive development at very early ages.

PMID- 18317893
TI  - Alcohol consumption by women before and during pregnancy.
AB  - OBJECTIVES: To determine the prevalence, patterns, and predictors of alcohol
      consumption prior to and during various intervals of pregnancy in the U.S.
      METHODS: Alcohol-related, pregnancy-related, and demographic data were derived
      from computer-assisted telephone interviews with 4,088 randomly selected control
      mothers from the National Birth Defects Prevention Study who delivered live born
      infants without birth defects during 1997-2002. Alcohol consumption rates and
      crude and adjusted odds ratios (OR) were calculated. RESULTS: 30.3% of all women
      reported drinking alcohol at some time during pregnancy, of which 8.3% reported
      binge drinking (4+ drinks on one occasion). Drinking rates declined considerably
      after the first month of pregnancy, during which 22.5% of women reported
      drinking, although 2.7% of women reported drinking during all trimesters of
      pregnancy and 7.9% reported drinking during the 3rd trimester. Pre-pregnancy
      binge drinking was a strong predictor of both drinking during pregnancy (adjusted
      OR = 8.52, 95% CI = 6.67-10.88) and binge drinking during pregnancy (adjusted OR
      = 36.02, 95% CI = 24.63-52.69). Other characteristics associated with both any
      drinking and binge drinking during pregnancy were non-Hispanic white
      race/ethnicity, cigarette smoking during pregnancy, and having an unintended
      pregnancy. CONCLUSIONS: Our study revealed that drinking during pregnancy is
      fairly common, three times the levels reported in surveys that ask only about
      drinking during the month before the survey. Women who binge drink before
      pregnancy are at particular risk for drinking after becoming pregnant. Sexually
      active women of childbearing ages who drink alcohol should be advised to use
      reliable methods to prevent pregnancy, plan their pregnancies, and stop drinking
      before becoming pregnant.

PMID- 18317894
TI  - Mother-to-infant emotional involvement at birth.
AB  - OBJECTIVES: To study mother-to-infant emotional involvement at birth, namely
      factors (socio-demographics, previous life events, type of delivery, pain at
      childbirth, support from partner, infant characteristics, early experiences with
      the newborn, and mother's mood) that interfere with the mother's positive,
      negative and not clear emotions toward the newborn. METHODS: The Bonding Scale
      (an extended Portuguese version of the 'New Mother-to-Infant Bonding Scale') and
      the Edinburgh Postnatal Depression Scale were administrated during the first
      after delivery days to 315 mothers recruited at Julio Dinis Maternity Hospital
      (MJD, Porto, Portugal). RESULTS: A worse emotional involvement with the newborn
      was observed when the mother was unemployed, unmarried, had less than grade 9,
      previous obstetrical/psychological problems or was depressed, as well as when the
      infant was female, had neonatal problems or was admitted in the intensive care
      unit. Lower total bonding results were significantly predicted when the mother
      was depressed and had a lower educational level; being depressed, unemployed and
      single predicted more negative emotions toward the infant as well. No significant
      differences in the mother-to-infant emotional involvement were obtained for
      events related to childbirth, such as type of delivery, pain and partner support,
      or early experiences with the newborn; these events do not predict mother's
      bonding results either. CONCLUSION: The study results support the need for
      screening and supporting depressed, unemployed and single mothers, in order to
      prevent bonding difficulties with the newborn at birth.

PMID- 18317915
TI  - Non-antiarrhythmic medications for atrial fibrillation: from bench to clinical
      practice.
AB  - Many treatment modalities have been developed over the years for the management
      of atrial fibrillation (AF). While they are still considered the first line of
      treatment for suppression of AF, antiarrhythmics often lead to treatment failure,
      complications and undesired consequences. Pulmonary vein ablation is an invasive
      procedure which is not always curative. Recently, there have been a variety of
      studies reporting the potential antiarrhythmic effects of various
      nonantiarrhythmic agents. This paper aims to provide a comprehensive review of
      the findings reported thus far about the antiarrhythmic effects of agents which
      are not antiarrhythmic drugs themselves, but which have been found to offer
      promise in the prevention and treatment of AF.

PMID- 18317916
TI  - Secondary prevention after acute myocardial infarction and coronary
      revascularisation: focus on Angiotensin converting enzyme inhibitors.
AB  - INTRODUCTION: Cardiovascular disease (CVD) is responsible for an estimated one
      third of all deaths worldwide. PATIENTS AND METHODS: One group of patients who
      are at a particularly high risk of cardiovascular events and death are those with
      stable coronary artery disease (CAD), especially if they have had a previous
      myocardial infarction (MI) or revascularisation. DISCUSSION: Lifestyle changes
      (smoking, alcohol intake, diet, exercise) and cardiac rehabilitation play an
      important part in reducing risk of recurrent events. In patients with a history
      of MI and/or those who underwent myocardial revascularisation these have to be
      supplemented with medication. Several pharmacological agents are known to improve
      prognosis in these patients, i.e. beta-blockers, antiplatelet agents, statins,
      and angiotensin converting enzyme inhibitors (ACEi). The present article focuses
      mainly on the role of ACEi in the prevention of cardiovascular events in patients
      with a history of MI or myocardial revascularization.

PMID- 18317917
TI  - Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in
      the viral nonstructural gene.
AB  - More and more H5N1 subtype avian influenza viruses possessing a 15-nucleotide (15
      nt) deletion in the viral nonstructural protein (NS) gene from position 263 to
      277 have emerged since 2000. In order to investigate the biological significance
      of this deletion, two pairs of H5N1 reassortants designated as rWSN-SD versus
      rWSN-mSD and rWSN-YZ versus rWSN-mYZ were generated by reverse genetics
      technique. These recombinant viruses shared the same inner genes of PB1, PB2, PA,
      NP, and M from strain A/WSN/33(H1N1) and outer genes of HA and NA from strain
      A/Duck/Shandong/093/2004 (H5N1) (A/D/SD/04), whereas they bore different NS gene.
      Recombinant rWSN-SD carried the full sequence NS gene from A/D/SD/04 in the
      natural state without deletion, whereas rWSN-mSD carried the same NS gene, but
      with an artificial 15-nt deletion from position 263 to 277. On the other hand,
      rWSN-YZ contained the NS gene in the natural state with a deletion from
      A/Duck/Yangzhou/232/2004 (H5N1) (A/D/YZ/04), while rWSN-mYZ bore the same NS gene
      but with an artificial insertion of 15-nt in site 263-277. All the four
      reassortants grew well in embryonated chicken eggs with similar mean death time
      (MDT) and viral titer of EID50 or HA. However, the virulence of these reassortant
      viruses in chickens and mice was different. Reassortant viruses with deletion in
      their NS gene (rWSN-mSD and rWSN-YZ) had much higher intraveneous pathogenicity
      index (IVPI) in chickens and lower MLD50 in mice than their counterparts without
      the deletion (rWSN-SD and rWSN-mYZ). Furthermore, rWSN-mSD and rWSN-YZ caused
      significantly more deaths in infected chickens and higher virus titers in tissues
      of inoculated mice than did rWSN-SD and rWSN-mYZ respectively. Sequence analysis
      also showed that H5N1 viruses carrying the 15-nt deletion in the NS gene
      invariably had the D92E shift in their NS1 protein. The results indicated that
      the 15-nucleotide deletion of NS gene from site 263 to 277 associated with D92E
      shift in NS1 protein contributes to the virulence increase of H5N1 viruses in
      chickens and mice.

PMID- 18317918
TI  - Parent ratings of ADHD symptoms: differential symptom functioning across
      Malaysian Malay and Chinese children.
AB  - This study examined differential symptom functioning (DSF) in ADHD symptoms
      across Malay and Chinese children in Malaysia. Malay (N=571) and Chinese (N=254)
      parents completed the Disruptive Behavior Rating Scale, which lists the DSM-IV
      ADHD symptoms. DSF was examined using the multiple indicators multiple causes
      (MIMIC) structural equation modeling procedure. Although DSF was found for a
      single inattention (IA) symptom and three hyperactivity-impulsivity (HI)
      symptoms, all these differences had low effect sizes. Controlling for these DSF,
      Chinese children had higher IA and HI latent factor scores. However the effect
      sizes were small. Together, these findings suggest adequate support for
      invariance of the ADHD symptoms across these ethno-cultural groups. The
      implications of the findings for cross-cultural invariance of the ADHD symptoms
      are discussed.

PMID- 18317919
TI  - Affective decision-making and externalizing behaviors: the role of autonomic
      activity.
AB  - We tested a conceptual model involving the inter-relations among affective
      decision-making (indexed by a gambling task), autonomic nervous system (ANS)
      activity, and attention-deficit/hyperactivity disorder (ADHD) and oppositional
      defiant disorder (ODD) symptoms in a largely impoverished, inner city sample of
      first through third grade children (N=63, 54% male). The present study
      hypothesized that impaired affective decision-making and decreased sympathetic
      and parasympathetic activation would be associated with higher levels of ADHD and
      ODD symptoms, and that low sympathetic and parasympathetic activation during an
      emotion-inducing task would mediate the relation between affective decision
      making and child externalizing symptoms. In support of our model, disadvantageous
      decision-making on a gambling task was associated with ADHD
      hyperactivity/impulsivity symptoms among boys, and attenuated sympathetic
      activation during an emotion-inducing task mediated this relation. Support for
      the model was not found among girls.

PMID- 18317920
TI  - Working memory deficits in boys with attention-deficit/hyperactivity disorder
      (ADHD): the contribution of central executive and subsystem processes.
AB  - The current study investigated contradictory findings from recent experimental
      and meta-analytic studies concerning working memory deficits in ADHD. Working
      memory refers to the cognitive ability to temporarily store and mentally
      manipulate limited amounts of information for use in guiding behavior.
      Phonological (verbal) and visuospatial (nonverbal) working memory were assessed
      across four memory load conditions in 23 boys (12 ADHD, 11 typically developing)
      using tasks based on Baddeley's (Working memory, thought, and action, Oxford
      University Press, New York, 2007) working memory model. The model posits separate
      phonological and visuospatial storage and rehearsal components that are
      controlled by a single attentional controller (CE: central executive). A latent
      variable approach was used to partial task performance related to three variables
      of interest: phonological buffer/rehearsal loop, visuospatial buffer/rehearsal
      loop, and the CE attentional controller. ADHD-related working memory deficits
      were apparent across all three cognitive systems--with the largest magnitude of
      deficits apparent in the CE--even after controlling for reading speed, nonverbal
      visual encoding, age, IQ, and SES.

PMID- 18317921
TI  - Research and action for bridging science and practice in prevention.
AB  - There is a well-known gap between science and practice. To address this gap in
      the areas of Child Maltreatment (CM) and Youth Violence (Y/V), the Division of
      Violence Prevention (DVP) at the Centers for Disease Control and Prevention (CDC)
      embarked on a Dissemination/Implementation (D/I) planning project. The project
      was aimed at identifying better ways to connect research and practice through
      reviews of the literature as well as through discussions with experts on violence
      prevention and research utilization. This introductory article sets the stage for
      the rest of the special issue by defining terms, providing a rationale for the
      planning project, describing the planning process, and summarizing what is to
      come in the rest of the issue.

PMID- 18317922
TI  - Assessing the cytoskeletal system and its elements in C6 glioma cells and
      astrocytes by atomic force microscopy.
AB  - OBJECT: To investigate how the characteristic structure of the cytoskeleton in
      glioma cells is associated with invasiveness. METHODS: The whole cytoskeletal
      system was characterized by atomic force microscopy (AFM), while single
      cytoskeletal elements were exhibited by AFM and using cytoskeletal protein
      inhibitors to inhibit microfilaments or/and microtubules and displayed by
      immunofluorescence microscopy. The fluorescence intensity of F-actin was measured
      by flow cytometry and the structural difference between C6 glioma cells and
      astrocytes was studied. RESULTS: Cytoskeletons in both cells presented network
      structures, however, the C6 glioma cells showed an irregular edge root and their
      microfilaments were creber and dense. Intermediate filaments were extensive
      network structure with non-polarized multipoint connections. The microtubules
      were relatively big and long and formed tight bundles with close connections
      between bundles. Astrocytes had a regular and smooth edge, with sparse
      microfilaments, while the intermediate filaments were dense and interwoven and
      the microtubules were dense bundled, but only loosely connected each other.
      Besides, the fluorescence intensity of F-actin was significantly higher in C6
      glioma cells (202.54 +/- 11.06) than in the astrocytes (62.64 +/- 10.23), P <
      0.01. CONCLUSION: Whole cytoskeleton and its elements of C6 cells were disclosed
      of characteristic structures associated with invasiveness. Meanwhile, the content
      of F-actin could be used as a parameter for measuring cell invasiveness.

PMID- 18317923
TI  - Cardiorespiratory and metabolic changes during yoga sessions: the effects of
      respiratory exercises and meditation practices.
AB  - The novelty of this study was to investigate the changes in cardiorespiratory and
      metabolic intensity brought about by the practice of pranayamas (breathing
      exercises of yoga) and meditation during the same hatha-yoga session. The
      technique applied was the one advocated by the hatha-yoga system. Nine yoga
      instructors-five females and four males, mean age of 44+/-11, 6, were subjected
      to analysis of the gases expired during three distinct periods of 30 min: rest,
      respiratory exercises and meditative practice. A metabolic open circuit
      computerized system was applied (VO2000, MedGraphics-USA). The oxygen uptake
      (VO(2)) and the carbon dioxide output (VCO(2)) were statistically different (P
      <or= 0.05) during meditation and pranayama practices when compared with rest. The
      heart rate also suffered relevant reductions when results at rest were compared
      with those during meditation. A smaller proportion of lipids was metabolized
      during meditation practice compared with rest. The results suggest that the
      meditation used in this study reduces the metabolic rate whereas the specific
      pranayama technique in this study increases it when compared with the rest state.

PMID- 18317924
TI  - Receipt of adjuvant systemic therapy among patients with high-risk breast cancer
      detected by mammography screening.
AB  - BACKGROUND: Few studies have compared screen-detected (SD) breast cancer patients
      with symptomatic patients for the frequency and determinants of receipt of
      adjuvant systemic therapy according to accepted guidelines. METHODS: Depending on
      the date of diagnosis, adjuvant therapy guidelines from the 5th, 6th, and 7th St.
      Gallen International Conferences were used as standards to audit the treatment of
      598 node-negative high-risk patients (59% SD) and 430 node-positive patients (40%
      SD) aged 50-69 years from an Italian cancer registry (1997-2001). Odds ratios
      (OR) and 95% confidence intervals (CI) were calculated using backward stepwise
      logistic regression models. RESULTS: Among node-negative high-risk patients, SD
      cancers were smaller (P = 0.000) and of lower grade (P = 0.003). Downgrading was
      generally from grade 3 to grade 2, with an increased proportion of patients
      placed in the high-risk category due to grade 2 alone. The total rates of
      adjuvant systemic therapy were similar (58 vs. 60%) whereas SD patients were less
      often treated according to the guidelines (34 vs. 45%; OR = 0.61; 95% CI, 0.44
      0.86). After adjustment for tumour size and other weaker confounders, the OR was
      0.99 (95% CI, 0.67-1.46). Among node-positive patients, the OR of receiving the
      standard adjuvant systemic therapy did not differ between SD and symptomatic
      cancers. CONCLUSIONS: SD cancers amplified the prognostic heterogeneity of node
      negative high-risk patients. Their lower likelihood of being treated according to
      the guidelines was largely explained by their lower risk profile. No evidence was
      found to suggest that physicians held a priori assumptions about the relative
      biological indolence of SD cancers.

PMID- 18317925
TI  - Brain atrophy in a murine model of chronic fatigue syndrome and beneficial effect
      of Hochu-ekki-to (TJ-41).
AB  - Brain-derived neurotrophic factor (BDNF) is associated with the main symptoms of
      chronic fatigue syndrome (CFS) and neuron apoptosis. Nevertheless, no study has
      been performed directly to explore the relationship between CFS, BDNF and neuron
      apoptosis. We induced a CFS model by six injections of killed Brucella abortus
      antigen in BALB/c mice and treated them with Hochu-ekki-to (TJ-41). Daily running
      activity, body weight (BW), ratio of cerebral weight to BW (CW/BW) and expression
      levels of BDNF and Bcl-2 mRNA in the hippocampus were determined. The daily
      activity and CW/BW decreased significantly in the CFS model. BDNF and Bcl-2 mRNA
      expression levels in the hippocampus were suppressed in the CFS model and TJ-41
      treated mice, while no significant difference was found between them. We improved
      a murine model to investigate the relationship between CFS and brain dysfunction.
      In this model, reduced daily activity might have been associated with decreased
      hippocampal BDNF mRNA expression, hippocampal apoptosis and brain atrophy. TJ-41
      increased the daily running activity of the model, which was independent of brain
      recovery.

PMID- 18317926
TI  - Translocation of amyloid precursor protein C-terminal fragment(s) to the nucleus
      precedes neuronal death due to thiamine deficiency-induced mild impairment of
      oxidative metabolism.
AB  - Thiamine deficiency (TD) is a model of neurodegeneration induced by mild
      impairment of oxidative metabolism. TD produces time-dependent glial activation,
      inflammation, oxidative stress, altered metabolism of amyloid precursor protein
      (APP), exacerbation of plaque formation from APP, and finally, selective neuron
      death in specific brain regions. The sub-medial thalamic nucleus (SmTN) is the
      most sensitive region to TD. Alteration in APP metabolism and nuclear
      translocation of carboxy-terminal fragments (CTF) of APP has been implicated in
      neuron death in other models of neurodegeneration. These experiments tested
      whether TD causes translocation of CTF into the nucleus of neurons in the SmTN
      that are destined to die after 9 days of TD by examining overlapping
      immunoreactivity (IR) of antibody APP 369 with either Alz90, 6E10 or 4G8 epitopes
      in the nuclei of the neurons in the SmTN. TD caused the accumulation of the CTF
      of APP in nuclei of SmTN neurons within 3 days of TD. These changes did not occur
      in the cortex which is spared in TD. Western blot analysis of nuclear fractions
      revealed a significant (61%; P < 0.026) increase in CTF 12 levels in TD SmTN
      (2.08 +/- 0.56) compared to control SmTN (1.29 +/- 0.41). Although TD increased
      CTF 15 levels in TD SmTN (1.95 +/- 0.73) compared to control SmTN (0.62 +/- 0.52)
      by 214%; P < 0.665 and decreased the full-length holo-APP levels in TD SmTN (0.32
      +/- 0.30) compared to control SmTN (0.47 +/- 0.18) by 34%; P < 0.753, the
      differences were statistically insignificant. TD did not alter CTF 15 or CTF 12
      levels in cortex. These findings demonstrate that changes in APP metabolism occur
      in early stages of TD, and they may play an important role in TD-induced
      selective neuronal loss.

PMID- 18317927
TI  - Historical change in the link between adolescent deviance proneness and marijuana
      use, 1979-2004.
AB  - We examined historical change in the association between adolescent deviance
      proneness and marijuana use using 26 years (from 1979 through 2004) of national
      12th grade data from the Monitoring the Future (MTF) study. "Deviance proneness"
      was measured using a latent factor model of behavioral and personality
      characteristics that underlie both substance use and antisocial disorders.
      Marijuana use was measured both in terms of annual frequency of use and degree of
      involvement with marijuana. Separate within-gender structural equation models
      were used to determine whether links between deviance proneness and marijuana use
      were consistently significant and invariant in magnitude across 13 two-year
      historical cohorts. Overall results affirmed the established association between
      adolescent deviance proneness and both the frequency of marijuana use as well as
      regular use. Among male youth, the size of the association between deviance
      proneness and marijuana use was significantly smaller at the cohort of lowest
      population prevalence (1991/92) compared to cohorts marking peaks in marijuana
      use prevalence, thus suggesting a "softening" historical trend. By contrast, the
      prediction of female marijuana use from deviance proneness was not consistently
      related to historical shifts in population prevalence of marijuana use. Study
      findings point to the utility of risk-focused prevention programming that targets
      early precursors of both antisocial and substance use disorders.

PMID- 18317928
TI  - Optimality in the variation of average branching angle with generation in the
      human bronchial tree.
AB  - In the human bronchial tree the branching angle becomes larger with generation or
      for the smaller branches. Previous theories based on single parameter
      optimization have not been successful at all in predicting the consistent
      increasing trend of branching angle with continued bifurcation. In this study a
      new theory for the optimality of the branching angle is proposed, which is based
      on the optimization between dual competing performances, the maximum space
      filling capability at the expense of minimum energy loss. A large-angle branching
      gives an effect of delivering air into a new direction away from the preceding
      airways. It then has an effect of utilizing the lung volume with better
      uniformity, but at the same time inevitably requires a high pressure loss. It is
      shown in this paper that the ever increasing branching angle with generation can
      be well explained as the optimum branching structure where the dual opposing
      performance of space filling and pressure loss is optimized. In estimating the
      pressure loss, branching loss is considered in addition to the Poiseuille loss.
      Change of predicted optimum branching angle with generation shows an excellent
      agreement with the observed data found in the human conducting airways.

PMID- 18317929
TI  - Anatomically realistic three-dimensional meshes of the pelvic floor & anal canal
      for finite element analysis.
AB  - Three anatomically realistic meshes, suitable for finite element analysis, of the
      pelvic floor and anal canal regions have been developed to provide a framework
      with which to examine the mechanics, via finite element analysis of normal
      function within the pelvic floor. Two cadaver-based meshes were produced using
      the Visible Human Project (male and female) cryosection data sets, and a third
      mesh was produced based on MR image data from a live subject. The Visible Man
      (VM) mesh included 10 different pelvic structures while the Visible Woman and MRI
      meshes contained 14 and 13 structures, respectively. Each image set was digitized
      and then finite element meshes were created using an iterative fitting procedure
      with smoothing constraints calculated from 'L'-curves. These weights produced
      accurate geometric meshes of each pelvic structure with average Root Mean Square
      (RMS) fitting errors of less than 1.15 mm. The Visible Human cadaveric data
      provided high resolution images, however, the cadaveric meshes lacked the normal
      dynamic form of living tissue and suffered from artifacts related to postmortem
      changes. The lower resolution MRI mesh was able to accurately portray structure
      of the living subject and paves the way for dynamic, functional modeling.

PMID- 18317930
TI  - Microvascular endothelial cells exhibit optimal aspect ratio for minimizing flow
      resistance.
AB  - A recent analytical solution of the three-dimensional Stokes flow through a bumpy
      tube predicts that for a given bump area, there exists an optimal circumferential
      wavenumber which minimizes flow resistance. This study uses measurements of
      microvessel endothelial cell morphology to test whether this prediction holds in
      the microvasculature. Endothelial cell (EC) morphology was measured in blood
      perfused in situ microvessels in anesthetized mice using confocal intravital
      microscopy. EC borders were identified by immunofluorescently labeling the EC
      surface molecule ICAM-1 which is expressed on the surface but not in the EC
      border regions. Comparison of this theory with extensive in situ measurements of
      microvascular EC geometry in mouse cremaster muscle using intravital microscopy
      reveals that the spacing of EC nuclei in venules ranging from 27 to 106 microm in
      diameter indeed lies quite close to this predicted optimal configuration.
      Interestingly, arteriolar ECs are configured to minimize flow resistance not in
      the resting state, but at the dilated vessel diameter. These results raise the
      question of whether less organized circulatory systems, such as that found in
      newly formed solid tumors or in the developing embryo, may deviate from the
      optimal bump spacing predicted to minimize flow resistance.

PMID- 18317931
TI  - Differential regulation of neutrophil CD18 integrin function by di- and tri
      valent cations: manganese vs. gadolinium.
AB  - Affinity regulation of integrin function plays an important role during both
      leukocyte-endothelial and leukocyte-leukocyte interactions. We compared the roles
      of Mn(2+) (Manganese) and Gd(3+) (Gadolinium) in regulating leukocyte CD18
      integrin function. We observed that: (i) Both cations prolonged neutrophil
      homotypic aggregation following chemoattractant IL-8 stimulation, with Gd(3+)
      being effective at doses two orders of magnitude (10 microM range) lower that
      Mn(2+). (ii) While both Gd(3+) and Mn(2+) mediate homotypic cell aggregation via
      L: -selectin and CD18 integrins, their effects on the integrin subunits, LFA-1
      (CD11a/CD18) and Mac-1 (CD11b/CD18), was different. Gd(3+) altered both LFA-1 and
      Mac-1 function, while the dominant effect of Mn(2+) was on Mac-1. This effect of
      Gd(3+) on LFA-1 function was confirmed in cell-free studies that measured the
      binding of recombinant ICAM-1 to LFA-1 immobilized on beads. (iii) Both ions
      augmented the binding of 327C, an antibody that recognizes active CD18 on human
      neutrophils, both in the presence and absence of exogenous IL-8. The effects of
      Mn(2+) was more pronounced since it caused 3-4-fold increase in mAb 327C binding
      to neutrophils compared to Gd(3+) which increased antibody binding by only
      approximately 80%. 327C binding was partially reduced by Ca(2+). Further, 327C
      binding induced by Mn(2+) did not correlate tightly with cell adhesion function.
      (iv) In studies that monitored intracellular Ca(2+) ([Ca(2+)](i)), the addition
      of Mn(2+) but not Gd(3+) to neutrophils altered [Ca(2+)](i) levels. Overall,
      while both Gd(3+) and Mn(2+) stabilize high affinity CD18 mediated cell adhesion,
      Gd(3+) affects integrin conformation while Mn(2+) may also trigger other effects.

PMID- 18317932
TI  - New Year's Day.

PMID- 18317933
TI  - Liver protective effects of Morinda citrifolia (Noni).
AB  - This study evaluated the protective effects of Noni fruit juice on acute liver
      injury induced by carbon tetrachloride (CCl(4)) in female Sprague-Dawley (SD)
      rats. Liver damage (micro-centrilobular necrosis) was observed in animals
      pretreated with 20% placebo (drinking water) + CCl(4). However, pretreatment with
      20% Noni juice in drinking water + CCl(4) resulted in markedly decreased
      hepatotoxic lesions. Furthermore, serum alanine aminotransferase and aspartate
      aminotransferase levels were significantly lower in the Noni group than the
      placebo group. In a correlative time-dependent study, one dose of CCl(4) (0.25
      mL/kg in corn oil, p.o.) in female SD rats, pretreated with 10% placebo for 12
      days, caused sequential progressive hepatotoxic lesions over a 24 h period, while
      a protective effect from 10% Noni juice pretreatment was observed. These results
      suggest that Noni juice is effective in protecting the liver from extrinsic toxin
      exposure.

PMID- 18317934
TI  - Broadband homonuclear TOCSY with amplitude and phase-modulated RF mixing schemes.
AB  - We have explored the design of broadband scalar coupling mediated (13)C-(13)C and
      cross-relaxation suppressed (1)H-(1)H TOCSY sequences employing phase/amplitude
      modulated inversion pulses. Considering a variety of supercycles, pulsewidths and
      a RF field strength of 10 kHz, the Fourier coefficients defining the amplitude
      and phase modulation profiles of the 180 degrees pulses were optimised
      numerically so as to obtain efficient magnetisation transfer within the desired
      range of resonance offsets. The coherence transfer characteristics of the mixing
      schemes were assessed via numerical simulations and experimental measurements and
      were compared with commonly used sequences based on rectangular RF pulses. The
      efficacies of the clean (1)H-(1)H TOCSY sequences were also examined via
      numerical simulations for application to weakly oriented systems and sequences
      with efficient, broadband and clean dipolar transfer characteristics were
      identified. In general, the amplitude and phase modulated TOCSY sequences
      presented here have moderately better performance characteristics than the
      sequences currently employed in biomolecular NMR spectroscopy.

PMID- 18317935
TI  - Identification of candidate CBF genes for the frost tolerance locus Fr-Am2 in
      Triticum monococcum.
AB  - A cluster of eleven CBF genes was recently mapped to the Frost resistance-2 (Fr
      Am2) locus on chromosome 5 of diploid wheat (Triticum monococcum) using a cross
      between frost tolerant accession G3116 and frost sensitive DV92. The Fr-Am2 locus
      was mapped at the peak of two overlapping quantitative trait loci (QTL), one for
      frost survival and the other for differential expression of the cold regulated
      gene COR14b. Seven lines with recombination events within the CBF cluster were
      used to identify CBF candidate genes for these QTL. The lines carrying the
      critical recombination events were tested for whole plant frost survival and for
      differential transcript levels of cold induced COR14b and DHN5 genes. The
      strongest effect for these traits was associated to the linked TmCBF12, TmCBF14
      and TmCBF15 genes, with the G3116 allele conferring improved frost tolerance and
      higher levels of COR14b and DHN5 transcript at mild cold temperatures (12-15
      degrees C) than the DV92 allele. Comparison of CBF protein sequences revealed
      that the DV92 TmCBF12 protein contains a deletion of five amino acids in the AP2
      DNA binding domain. Electrophoretic Mobility Shift Assays (EMSA) confirmed that
      the protein encoded by this allele cannot bind to the CRT/DRE (C-repeat/
      dehydration-responsive element) motif present in the promoters of several cold
      induced genes. A smaller effect on frost tolerance was mapped to the distal group
      of CBF genes including TmCBF16. Transcript levels of TmCBF16, as well as those of
      TmCBF12 and TmCBF15 were up-regulated at mild cold temperatures in G3116 but not
      in DV92. Higher threshold induction temperatures can result in earlier initiation
      of the cold acclimation process and better resistance to subsequent freezing
      temperatures. The non-functional TmCBF12 allele in DV92 can also contribute to
      its lower frost tolerance.

PMID- 18317936
TI  - 7beta-Hydroxycholesterol and 25-hydroxycholesterol-induced interleukin-8
      secretion involves a calcium-dependent activation of c-fos via the ERK1/2
      signaling pathway in THP-1 cells: oxysterols-induced IL-8 secretion is calcium
      dependent.
AB  - Oxysterols found in oxidized low-density lipoproteins are probably involved in
      the appearance of atheroma; some are cytotoxic and some able to induce cytokine
      secretion. An oxysterol-induced interleukin-8 (IL-8) secretion in human
      monocytes/macrophages has been previously noticed, but the mechanisms remained
      unclear. In this paper, we investigated the signaling pathways leading to the
      induction of IL-8 secretion in monocytic THP-1 cells treated with 7beta
      hydroxycholesterol, a cytototoxic oxysterol, or with 25-hydroxycholesterol, an
      oxysterol non-cytotoxic toward this cell line. The oxysterol-induced IL-8
      secretion appears to be a calcium-dependent phenomenon as shown by the use of
      calcium channel blockers, which strongly decreased IL-8 secretion and IL-8
      messenger RNA (mRNA) levels. Fluo-3 staining used in flow cytometry and video
      microscopy revealed an oxysterol-induced Ca(2+) influx, varying according to the
      oxysterol studied, leading to the activation of the MEK/ERK1/2 pathway as
      demonstrated by Western blot analysis. ERK activation led to an increase of c-fos
      mRNA and/or an activation of c-fos. Luciferase reporter gene assay using
      constructs of the human IL-8 gene promoter and Transam assay revealed the
      involvement of the AP-1 transcription factor in oxysterol-dependent IL-8
      secretion. These results demonstrate that oxysterol-induced IL-8 secretion is a
      calcium-dependent phenomenon involving the MEK/ERK1/2 pathway leading to the
      activation of IL-8 gene via AP-1 (c-fos).

PMID- 18317937
TI  - Integrative sediment quality assessment using a biomarker approach: review of 3
      years of field research.
AB  - Recent research efforts in sediment and dredged material assessment research have
      focused on the inclusion of sublethal endpoints (biomarkers) in acute and long
      term bioassays for dredged material characterisation and management. The
      incorporation of biomarkers as a new line of evidence in a weight of evidence
      approach allows the determination of more sensitive, longer-term biological
      information for use in laboratory and in situ sediment/tissue quality guidelines.

PMID- 18317938
TI  - In memoriam Dr. Judah Folkman.

PMID- 18317939
TI  - Using remote sensing and GIS to detect and monitor land use and land cover change
      in Dhaka Metropolitan of Bangladesh during 1960-2005.
AB  - This paper illustrates the result of land use/cover change in Dhaka Metropolitan
      of Bangladesh using topographic maps and multi-temporal remotely sensed data from
      1960 to 2005. The Maximum likelihood supervised classification technique was used
      to extract information from satellite data, and post-classification change
      detection method was employed to detect and monitor land use/cover change.
      Derived land use/cover maps were further validated by using high resolution
      images such as SPOT, IRS, IKONOS and field data. The overall accuracy of land
      cover change maps, generated from Landsat and IRS-1D data, ranged from 85% to
      90%. The analysis indicated that the urban expansion of Dhaka Metropolitan
      resulted in the considerable reduction of wetlands, cultivated land, vegetation
      and water bodies. The maps showed that between 1960 and 2005 built-up areas
      increased approximately 15,924 ha, while agricultural land decreased 7,614 ha,
      vegetation decreased 2,336 ha, wetland/lowland decreased 6,385 ha, and water
      bodies decreased about 864 ha. The amount of urban land increased from 11% (in
      1960) to 344% in 2005. Similarly, the growth of landfill/bare soils category was
      about 256% in the same period. Much of the city's rapid growth in population has
      been accommodated in informal settlements with little attempt being made to limit
      the risk of environmental impairments. The study quantified the patterns of land
      use/cover change for the last 45 years for Dhaka Metropolitan that forms valuable
      resources for urban planners and decision makers to devise sustainable land use
      and environmental planning.

PMID- 18317940
TI  - Distribution of endocrine disruptors in the Mondego River estuary, Portugal.
AB  - Recent studies in the Mondego River estuary demonstrated signs of pollution in
      the area, but the nature of the contamination remains unexplored. Because there
      seems to be any studies in that zone checking for the simultaneous presence of
      xenoestrogenic endocrine disrupting compounds, either of animal (estradiol and
      estrone), vegetal (daidzein, genistein and biochanin A), pharmaceutical (17alpha
      ethynylestradiol) or industrial (bisphenol A, 4-octylphenol, 4-nonylphenol)
      origins, the main objective of this study was to investigate their presence, in
      every year season and at eight points along the estuarine gradient. For this
      propose, water samples (2 L) were collected in high and low tides,
      preconcentrated in the Oasis HLB cartridges and cleaned in silica cartridges
      before their analysis by HPLC-DAD and GC-MS. The current data showed the absence
      of contamination by animal or pharmaceutical estrogens and by alkylphenols, but
      demonstrated the presence of high levels of phytoestrogens (up to 1.1 mug/L) and
      of bisphenol A (up to 880.0 ng/L). Because these two chemicals existed in high
      environmental concentrations in the most upstream sampling station, and taking in
      account that these pollutants may additively contribute to endocrine disruption,
      namely on fish, it was concluded that at least this particularly area of the
      Mondego estuary deserves continuous monitoring programmes.

PMID- 18317941
TI  - Exploring structure-selectivity relationships of biogenic amine GPCR antagonists
      using similarity searching and dynamic compound mapping.
AB  - We design and analyze compound selectivity sets of antagonists with differential
      selectivity against seven biogenic amine G-protein coupled receptors. The
      selectivity sets consist of a total of 267 antagonists and contain a spectrum of
      in part closely related molecular scaffolds. Each set represents a different
      selectivity profile. Using these com- pound sets, a systematic computational
      analysis of structure-selectivity relationships is carried out with different 2D
      similarity methods including fingerprints, recursive partitioning, clustering,
      and dynamic compound mapping. Screening calculations are performed in a
      background database containing nearly four million molecules. Fingerprint
      searching and compound mapping are found to enrich target-selective antagonists
      over family-selective ones. Dynamic compound mapping effectively discriminates
      database compounds from GPCR antagonists and consistently retains target
      selective antagonists during the final dimension extension levels. Furthermore,
      the widely used MACCS key fingerprint displays a strong tendency to distinguish
      between target- and family-selective GPCR antagonists. Taken together, the
      results indicate that different types of 2D similarity methods are capable of
      distinguishing closely related molecules having different selectivity. The
      reported compound benchmark system is made freely available in order to enable
      selectivity-oriented analyses using other computational approaches.

PMID- 18317942
TI  - Structural features of diverse ligands influencing binding affinities to estrogen
      alpha and estrogen beta receptors. Part II. Molecular descriptors calculated from
      conformation of the ligands in the complex resulting from previous docking study.
AB  - A QSAR study is reported, in which the relationship between chemical structure of
      a set of compounds and the binding affinity to human estrogen receptor alpha and
      beta (ER-alpha and ER-beta) is modelled. Counterpropagation neural networks are
      used to predict experimental binding affinity of a range of substances. Several
      compounds as estrogenic chemicals, phytoestrogens, and natural and synthetic
      estrogens are treated with a structure-based approach that involves the protein
      structure. The conformations obtained with a docking methodology are used to
      calculate molecular descriptors. The models are built up with the neural network
      training procedure, which encodes the information present in molecular
      descriptors and related binding affinities of the pre-selected training set of
      compounds. In order to reach the best possible models, a selection of the
      descriptors using genetic algorithm was conducted. The selection was directed by
      the error in the prediction of binding affinities of compounds from the test set.
      The final models obtained for estrogen receptor alpha and beta were tested with
      an external validation set and were compared with the models obtained from a
      receptor-independent approach reported in the accompanying paper.

PMID- 18317943
TI  - Counter propagation artificial neural networks modeling of an enantioselectivity
      of artificial metalloenzymes.
AB  - The counter propagation artificial neural networks (CP-ANNs) were used to develop
      a quantitative structure-selectivity relationship (QSSR) for a set of artificial
      metalloenzymes. The artificial metalloenzymes consist of biotinylated rhodium
      diphosphine complexes incorporated in streptavidin mutants acting as host
      protein. Such hybrid catalysts have been shown to be good enantioselective
      hydrogenation catalysts for acetamidoacrylic acid. The descriptor-based models
      were constructed to predict enantiomeric excess (%ee) on the basis of the
      catalyst structures originating from docking simulations. 3D molecular
      descriptors for the docked ligands structures were computed. The relative
      arrangement of guest and host molecules was coded using distance descriptors (Rh
      C(alpha) interatomic distances); the diversity of the mutant proteins at the
      position S112 was coded with molecular descriptors for the sequence of three
      neighboring amino acids (T111-S112X-G113). The selection of testing samples for
      the external model validation was based on the Kohonen mapping. The final model
      trained by two thirds of the entire dataset was characterized by satisfactory
      statistical parameters for the external test set (R = 0.953 and RMS = 16.8 %ee).
      The proposed procedure of docking-based descriptor generation thus appears as a
      promising alternative to the full characterization of the complex structure by
      experimental or computational methods.

PMID- 18317944
TI  - Gender and age differences in blood utilization and length of stay in radical
      cystectomy: a population-based study.
AB  - OBJECTIVE: Radical cystectomy is a major surgical procedure associated with
      significant blood loss and lengthy hospital stays. This surgical procedure is
      more challenging in women than men due to anatomical-based differences. We
      evaluated resource utilization and complication rates of patients undergoing
      radical cystectomy or exenteration using the Texas Hospital In-Patient Discharge
      Data Collection. METHODS: This was a retrospective study of 1,493 patients, 35
      years of age or older, who underwent radical cystectomy for bladder cancer from
      January 2000 to December 2003. We evaluated blood product charges, length of
      stay, and complication rates during hospitalization. RESULTS: In this sample, 24%
      of the patients (n = 356) were women. Overall, women had significantly increased
      blood product charges and length of stay compared to men, $1,392.87 vs. $718.21
      (P < 0.001) and 12.72 vs. 11.64 (P = 0.03), respectively. During hospitalization,
      26 of the patients died. No differences in mortality or complication rates were
      observed between men and women. Multivariate analysis showed that female sex (P <
      0.001) and age (P = 0.003) were independent predictors of increased blood product
      charges. Multivariate analysis showed that female sex (P = 0.015), age (P =
      0.003), and Charlson's comorbidity index >1 (P = 0.05) were predictors of longer
      length of stay. CONCLUSION: Women and older patients with bladder cancer are at
      risk of increased blood products utilization and length of hospital stay after a
      radical cystectomy. Appropriate postoperative care and referrals should improve
      postoperative outcomes for these vulnerable patients.

PMID- 18317945
TI  - Expression of p27((Kip1)), cyclin D3 and Ki67 in BPH, prostate cancer and hormone
      treated prostate cancer cells.
AB  - p27((Kip1)), cyclin D3 and Ki67 are the markers of DNA damage and cell
      proliferation. The goal of the current study was to analyze expression of the
      markers in benign and malignant prostate cancer tissues. Activity of p27((Kip1)),
      cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH,
      prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The
      tissue samples were derived by means of TURP or radical prostatectomy. Intensity
      of the expression was compared between the groups, and association was sought
      with clinical parameters. Total expression of p27((Kip1)) was significantly
      higher in BPH as compared with PCa. Epithelial marker expression was higher in
      HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal
      cells was negatively associated with the tumor stage and Gleason grades. Total
      Ki67 activity was positively correlated with patient age and serum PSA level.
      There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa)
      as compared with BPH. Epithelial and vascular marker expression was positively
      associated with tumor stage and Gleason grades. There was a positive correlation
      between cyclin D3 and serum PSA level. With the increase of Gleason grades,
      cyclin D3 expression increased significantly. Expression of p27((Kip1))
      negatively correlated with Ki67 and cyclin D3, while the latter two markers
      correlated positively. p27((Kip1)) is down-regulated, whereas Ki67 and cyclin D3
      are up-regulated in PCa. Intensity of the markers' expression is associated with
      tumor stage and grades. Hormonotherapy of PCa causes activation of p27((Kip1)).
      HEPCa is characterized by increased Ki67 expression.

PMID- 18317946
TI  - Premature senescence of human endothelial cells induced by inhibition of
      glutaminase.
AB  - Cellular senescence is now recognized as an important mechanism of tumor
      suppression, and the accumulation of senescent cells may contribute to the aging
      of various human tissues. Alterations of the cellular energy metabolism are
      considered key events in tumorigenesis and are also known to play an important
      role for aging processes in lower eukaryotic model systems. In this study, we
      addressed senescence-associated changes in the energy metabolism of human
      endothelial cells, using the HUVEC model of in vitro senescence. We observed a
      drastic reduction in cellular ATP levels in senescent endothelial cells. Although
      consumption of glucose and production of lactate significantly increased in
      senescent cells, no correlation was found between both metabolite conversion
      rates, neither in young endothelial cells nor in the senescent cells, which
      indicates that glycolysis is not the main energy source in HUVEC. On the other
      hand, glutamine consumption was increased in senescent HUVEC and inhibition of
      glutaminolysis by DON, a specific inhibitor of glutaminase, led to a significant
      reduction in the proliferative capacity of both early passage and late passage
      cells. Moreover, inhibition of glutaminase activity induced a senescent-like
      phenotype in young HUVEC within two passages. Together, the data indicate that
      glutaminolysis is an important energy source in endothelial cells and that
      alterations in this pathway play a role in endothelial cell senescence.

PMID- 18317947
TI  - Daily serotonin rhythms in rat brain during postnatal development and aging.
AB  - Aging is characterized by progressive decline in most physiological functions.
      The age-related sleep disturbances have been attributed to disturbances of
      circadian function. Neurotransmitter serotonin plays important role in the photic
      and non-photic regulation of circadian rhythms and is a precursor of melatonin,
      an internal zeitgeber. To understand the age induced changes in the functional
      integrity of circadian system, we studied daily serotonin rhythms in brain by
      measuring serotonin levels at variable time points in wide range of age groups
      such as 15 days, 1, 2, 3 (adult), 4, 6, 9, 12, 18 and 24-months old male Wistar
      rats. Animals were maintained under light-dark conditions (LD 12:12), 2 weeks
      prior to experiment. We report here, mean serotonin levels over 24 h period in
      brain is highest at 3 months and daily serotonin rhythmicity reliably begins at 3
      months and disintegrates at middle age and beyond. The age induced changes in
      daily serotonin rhythmicity in brain obtained in present study will be a step
      towards understanding age induced disorders of circadian function.

PMID- 18317948
TI  - Cloning and characterization of a soluble acid invertase-encoding gene from
      muskmelon.
AB  - Soluble acid invertase (S-AIV; EC 3.2.1.26) is thought to play a critical role in
      sucrose hydrolysis in muskmelon (Cucumis melo L.) fruit. A full-length cDNA clone
      encoding S-AIV was isolated from muskmelon by RT-PCR and RACE. The clone,
      designated as CmS-AIV1, contains 2178 nucleotides with an open reading frame of
      1908 nucleotides. The deduced 636 amino acid sequence showed high identities with
      other plant soluble acid invertases. Northern blot analysis indicated that CmS
      AIV1 was expressed in flowers and fruit, but was not detected in roots, stems or
      leaves. Moreover, the mRNA accumulation of CmS-AIV1 showed its maximum level at
      10 days after pollination (DAP) and decreased gradually during fruit development
      until its minimum level at mature fruit. Interestingly, the sucrose content was
      very low in fruit before 20 DAP but increased dramatically between 20 and 30 DAP
      during fruit development. In contrast to sucrose content, the activities of S-AIV
      was very high in fruit before 20 DAP and decreased apparently between 20 and 30
      DAP, suggesting that sucrose metabolism may be linked to the CmS-AIV1 transcript
      level in muskmelon fruit.

PMID- 18317949
TI  - Haplotype analysis revealed a genetic influence of osteopontin on large artery
      atherosclerosis.
AB  - Osteopontin (OPN) is a cytokine that involves in vascular remodeling processes in
      cerebrovascular diseases. The association of its gene with ischemic stroke was
      investigated in a Korean population. Representative sequence variants covering
      the entire OPN gene were genotyped in 455 controls and 271 patients with ischemic
      stroke including large artery atherosclerosis (LAA), small vessel occlusion, and
      cardioembolism. Analysis with the individual tagging variants and their
      haplotypes revealed an evidence of association only with LAA. Significances were
      shown with the haplotypes, especially with the TCA at the loci C2140T, C5891T,
      and A7385G conferring a risk of 2.09 for LAA (P < 0.05). The CG at the loci
      C1013T and A7385G was the most protective haplotype (OR = 0.66, P < 0.05). Our
      findings suggested that several haplotypes of OPN gene contributed to determining
      risk factors as well as protective factors of LAA.

PMID- 18317950
TI  - Differential phosphorylation of translation initiation regulators 4EBP1, S6k1,
      and Erk 1/2 following inhibition of alcohol metabolism in mouse heart.
AB  - Acute alcohol intoxication leads to an inhibition of protein synthesis in heart
      that results in part through altered phosphorylation of protein factors
      controlling mRNA translation initiation. The purpose of the present set of
      experiments was designed to examine the effects of inhibitors of ethanol
      metabolism on the phosphorylation of 4E-binding protein (4EBP1) and
      S6k1(Thr(389)), two factors regulating mRNA translation initiation.
      Phosphorylation of 4E-BP1, S6k1(Thr(389)), and Erk 1/2 was reduced 2 h following
      IP injection of alcohol. Pretreatment with 4-methylpyrazole (4-MP), an inhibitor
      of alcohol dehydrogenase (ADH), did not attenuate the ethanol-induced decrease in
      phosphorylation of 4EBP1 and S6k1(Thr(389)). In contrast, 4-MP prevented the
      decrease in Erk 1/2 phosphorylation observed with acute ethanol intoxication.
      Pretreatment with cyanamide, an inhibitor of aldehyde dehydrogenase, did not
      attenuate the ethanol-induced decrease in phosphorylation S6k1(Thr(389)), but
      partially prevented the ethanol-induced lowering of 4EBP1 phosphorylation. The
      studies indicate that modulation of ethanol metabolism through inhibition of ADH
      or aldehyde dehydrogenase leads to preferential modulation of the phosphorylation
      of distinct myocardial signaling systems involved in regulating protein
      synthesis.

PMID- 18317951
TI  - Calcium homeostasis during magnesium treatment in aneurysmal subarachnoid
      hemorrhage.
AB  - OBJECTIVE: Magnesium treatment in patients with subarachnoid hemorrhage (SAH) can
      result in hypocalcemia; this hypocalcemia increases the risk of delayed cerebral
      ischemia (DCI) and poor outcome. We assessed whether low serum levels of total
      calcium in patients with SAH treated with magnesium is mediated by parathyroid
      hormone (PTH) or calcitriol, and whether increased PTH or low serum levels of
      ionized calcium are associated with an increased risk of DCI and poor outcome.
      PATIENTS AND METHODS: We studied 167 patients included in a randomized, placebo
      controlled trial on magnesium in SAH. Mean serum magnesium during treatment was
      related to mean serum levels of ionized calcium, PTH and calcitriol with linear
      regression. Hypocalcemia (Ca(2+)) and high serum PTH were related to the
      occurrence of DCI by means of the Cox proportional hazards model and to poor
      outcome by logistic regression. RESULTS: Serum magnesium was inversely related to
      ionized calcium (B = -0.1; 95% CI -0.12 to -0.06), but not to PTH or calcitriol.
      Neither hypocalcemia nor high serum PTH was related to DCI. Hypocalcemia did not
      increased the risk for poor outcome (OR 1.2; 95% CI 0.6-2.3). In the subgroup of
      patients with known PTH (n = 67), high serum PTH increased the risk for poor
      outcome (OR 5.4; 1.6-18.9). CONCLUSIONS: Magnesium treatment in patients with SAH
      leads to hypocalcemia without effect on outcome. PTH is related to poor outcome,
      but this is independent of magnesium therapy.

PMID- 18317952
TI  - Adrenergic differentiation and Ret expression in rat pheochromocytomas.
AB  - Pheochromocytomas are catecholamine-producing tumors of the adult adrenal
      medulla. They are rare in humans and most other species but common in laboratory
      rats. However, the relevance of rat pheochromocytomas as a model for their human
      counterparts is uncertain. Previous studies of spontaneous and drug-induced rat
      pheochromocytomas and the PC12 pheochromocytoma cell line suggested a distinctive
      noradrenergic phenotype, possibly reflecting origin from a progenitor not present
      in the adult human adrenal. In this study, we studied 31 pheochromocytomas
      derived from test and control male and female rats in toxicologic studies for
      expression of the epinephrine-synthesizing enzyme phenylethanolamine-N
      methyltransferase (PNMT) and the receptor tyrosine kinase Ret. PNMT, which
      defines adrenergic chromaffin cells, is frequently expressed in human
      pheochromocytomas, often in tumors that also overexpress RET. We also tested for
      the expression of the cell cycle checkpoint protein p27(Kip1), which recently was
      reported absent in pheochromocytomas from a strain of rats with a hereditary
      mixed multiple endocrine neoplasia (MEN)-like syndrome. Using immunoblots, we
      demonstrated PNMT expression in almost 50% of the 31 tumors, although often at
      lower levels than in normal rat adrenal medulla. The majority of tumors
      overexpressed Ret. There was no apparent correlation between PNMT and Ret.
      However, in this study, PNMT expression was strongly associated with tumors
      arising in female rats, while overexpression of Ret did not show a sex
      predilection. Robust expression of p27(Kip1) was seen in all tumors from the
      toxicologic studies and also in a small sample of pheochromocytomas from Long
      Evans rats, which were reported to have a mixed MEN-like syndrome in the 1980s.
      The present results show that rat pheochromocytomas have greater phenotypic
      diversity than previously believed and greater similarity to their human
      counterparts with respect to these two important markers. Loss of p27(Kip1) does
      not appear to account for the high frequency of pheochromocytomas in commonly
      utilized rat strains.

PMID- 18317953
TI  - Silent familial isolated pituitary adenomas: histopathological and clinical case
      report.
AB  - Familial isolated pituitary adenoma (FIPA) is a rare condition independent of
      Carney Complex or MEN1. An international multicenter study recently described 28
      nonfunctioning pituitary adenomas in 26 families with only two homogeneous
      nonsecreting phenotype families consistent of silent GH and silent gonadotroph
      adenomas, respectively. We present the clinical, genetic, and morphological
      analysis of two silent pituitary adenomas occurring in a man and his daughter,
      and discuss the differential diagnosis associated with their histological,
      immunohistochemical, and ultrastructural features. The patients developed
      invasive nonsecreting macroadenomas manifesting only with compressive symptoms.
      Genetic analysis in the father showed no MEN-1 germ-line mutation. Tissue samples
      obtained after paraseptal trans-sphenoidal surgery were studied by
      immunohistochemistry for adenohypophyseal hormones, low molecular weight
      cytokeratins (CAM 5.2), proliferation markers, and anterior pituitary
      transcription factors (Pit-1 and SF-1) and by electron microscopy for secretory
      granules. The clinical, histological, and immunohistochemical features of the
      lesions posed a differential diagnosis between a null cell adenoma and a silent
      corticotroph adenoma (Type II); on the basis of immunohistochemical stains for
      cytokeratin and adenohypophysis cell lineage markers, tumor behavior and
      ultrastructural studies we concluded for the second. The reported cases represent
      an as yet undescribed example of homogeneous family with silent corticotroph
      adenomas (Type II). Our observations support the trend for more aggressive
      behavior in nonsecreting FIPAs as compared with sporadic adenomas.

PMID- 18317954
TI  - Prognostic and predictive value of vascular endothelial growth factor and its
      soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung
      cancer patients.
AB  - OBJECTIVES: Small cell lung cancer (SCLC) has a rapid growth rate and is
      characterized by early metastases. Tumor growth is dependent on angiogenesis.
      Vascular endothelial growth factor (VEGF) is an important regulator of
      angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and
      especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on
      clinical outcome is unknown. METHODS: From February 2001 to January 2003, 39
      consecutive patients with histological proven SCLC were enrolled into the study.
      Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients
      were collected at the time of their response evaluation. The levels of VEGF and
      its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative
      sandwich enzyme immunoassay technique. RESULTS: The median pre-treatment serum
      VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal
      controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8
      +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively.
      We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p:
      0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good
      response to treatment (p: 0.008) were found as good prognostic factors by
      multivariate analysis. CONCLUSIONS: Low serum VEGF concentration is a significant
      and independent prognostic factor in SCLC patients. Surveillance of VEGF and its
      receptors to predict chemotherapy response is not useful. Whether the levels of
      serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting
      treatment modalities of SCLC need further studies.

PMID- 18317955
TI  - The present and the future of breast cancer burden in the Kingdom of Saudi
      Arabia.
AB  - BACKGROUND: Despite the low cancer incidence in the Kingdom of Saudi Arabia
      (KSA), the country must be ready to face the challenge of foreseeable increase in
      cancer burden attributed to growth and aging of population. This work was
      designed to study female breast cancer as a model to assess future cancer burden
      and the impact on healthcare resources. METHODS: Cancer statistics for the KSA
      were compared with that for the USA. The Joinpoint regression program was used to
      identify changes in secular trends, while the GLOBOCAN 2002 software projected
      future incidence and mortality. RESULTS: In the KSA, the age-standardized cancer
      rate (ASR) is 61 per 100,000 population, while the median age at diagnosis is 54
      and 49 years for men and women, respectively. Fitting the ASR for breast cancer
      did not show any significant trend over a 10-year calendar period (16.2-18.2 per
      100,000), a pattern that was similar to that for the USA in the prescreening
      mammography era. Considering the growth and aging of population and using
      conservative estimates for the annual percent change in incidence (increase) and
      mortality (decrease) by 2025, incidence and mortality cases are expected to
      increase by about 350% and 160%, respectively. CONCLUSION: In developing
      countries, future cancer rates could demonstrate a considerable increase and
      enormous demands on healthcare resources. The present work may provide an impetus
      to study other prevalent cancer types particularly in developing countries.

PMID- 18317956
TI  - Providing metrics and performance feedback in a surgical simulator.
AB  - One of the most important advantages of computer simulators for surgical training
      is the opportunity they afford for independent learning. However, if the
      simulator does not provide useful instructional feedback to the user, this
      advantage is significantly blunted by the need for an instructor to supervise and
      tutor the trainee while using the simulator. Thus, the incorporation of relevant,
      intuitive metrics is essential to the development of efficient simulators.
      Equally as important is the presentation of such metrics to the user in such a
      way so as to provide constructive feedback that facilitates independent learning
      and improvement. This paper presents a number of novel metrics for the automated
      evaluation of surgical technique. The general approach was to take criteria that
      are intuitive to surgeons and develop ways to quantify them in a simulator.
      Although many of the concepts behind these metrics have wide application
      throughout surgery, they have been implemented specifically in the context of a
      simulation of mastoidectomy. First, the visuohaptic simulator itself is
      described, followed by the details of a wide variety of metrics designed to
      assess the user's performance. We present mechanisms for presenting
      visualizations and other feedback based on these metrics during a virtual
      procedure. We further describe a novel performance evaluation console that
      displays metric-based information during an automated debriefing session.
      Finally, the results of several user studies are reported, providing some
      preliminary validation of the simulator, the metrics, and the feedback
      mechanisms. Several machine learning algorithms, including Hidden Markov Models
      and a Naive Bayes Classifier, are applied to our simulator data to automatically
      differentiate users' expertise levels.

PMID- 18317957
TI  - Virtual reality-enhanced ultrasound guidance: a novel technique for intracardiac
      interventions.
AB  - Cardiopulmonary bypass surgery, although a highly invasive interventional
      approach leading to numerous complications, is still the most common therapy
      option for treating many forms of cardiac disease. We are currently engaged in a
      project designed to replace many bypass surgeries with less traumatic, minimally
      invasive intracardiac therapies. This project combines real-time intra-operative
      echocardiography with a virtual reality environment providing the surgeon with a
      broad range of valuable information. Pre-operative images, electrophysiological
      data, positions of magnetically tracked surgical instruments, and dynamic
      surgical target representations are among the data that can be presented to the
      surgeon to augment intra-operative ultrasound images. This augmented reality
      system is applicable to procedures such as mitral valve replacement and atrial
      septal defect repair, as well as ablation therapies for treatment of atrial
      fibrillation. Our goal is to develop a robust augmented reality system that will
      improve the efficacy of intracardiac treatments and broaden the range of cardiac
      surgeries that can be performed in a minimally invasive manner. This paper
      provides an overview of our interventional system and specific experiments that
      assess its pre-clinical performance.

PMID- 18317958
TI  - Surgery with cooperative robots.
AB  - Advances in endoscopic techniques for abdominal procedures continue to reduce the
      invasiveness of surgery. Gaining access to the peritoneal cavity through small
      incisions prompted the first significant shift in general surgery. The complete
      elimination of external incisions through natural orifice access is potentially
      the next step in reducing patient trauma. While minimally invasive techniques
      offer significant patient advantages, the procedures are surgically challenging.
      Robotic surgical systems are being developed that address the visualization and
      manipulation limitations, but many of these systems remain constrained by the
      entry incisions. Alternatively, miniature in vivo robots are being developed that
      are completely inserted into the peritoneal cavity for laparoscopic and natural
      orifice procedures. These robots can provide vision and task assistance without
      the constraints of the entry incision, and can reduce the number of incisions
      required for laparoscopic procedures. In this study, a series of minimally
      invasive animal-model surgeries were performed using multiple miniature in vivo
      robots in cooperation with existing laparoscopy and endoscopy tools as well as
      the da Vinci Surgical System. These procedures demonstrate that miniature in vivo
      robots can address the visualization constraints of minimally invasive surgery by
      providing video feedback and task assistance from arbitrary orientations within
      the peritoneal cavity.

PMID- 18317959
TI  - Multimodal virtual bronchoscopy using PET/CT images.
AB  - OBJECTIVE: To demonstrate the possibilities, advantages and limitations of
      virtual bronchoscopy using data sets from positron emission tomography (PET) and
      computed tomography (CT). MATERIALS AND METHODS: Eight consecutive patients with
      non-small cell lung cancer (NSCLC) underwent PET/CT. PET was performed with a
      glucose analog, 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG), using a state
      of-the-art full-ring Pico-3D PET scanner. CT was performed with a venous-dominant
      contrast-enhanced phase using a 16-slice CT scanner. The tracheobronchial system
      was segmented using the CT data set with an interactive threshold interval volume
      growing segmentation algorithm. The primary tumors and lymph node metastases were
      segmented for virtual CT-bronchoscopy using the CT data set and for virtual
      hybrid bronchoscopy using the PET/CT data set. The structures of interest were
      visualized with a color-coded shaded-surface rendering method. RESULTS: The use
      of CT and virtual CT-bronchoscopy primarily facilitates visualization of the
      anatomical details of the tracheobronchial system and detection of
      anatomical/morphologic structural changes caused by disease. PET/CT and virtual
      hybrid bronchoscopy, or virtual PET/CT-bronchoscopy, give superior results to
      virtual CT-bronchoscopy because the hybrid bronchoscopy uses both the CT
      information and the molecular/metabolic information about the disease obtained
      from PET. CONCLUSIONS: PET/CT imaging has proven to be a highly valuable
      oncological diagnostic modality. Virtual hybrid bronchoscopy can be performed
      using a low-dose CT scan or diagnostic CT. However, it is expected to improve
      diagnostic accuracy in identification and characterization of malignancies,
      verification of infections, and differentiation of viable tumor tissue from
      atelectases and scar tissue, as well as assessment of tumor staging and
      therapeutic response, and detection of early stage recurrences that are not
      detectable or are liable to be misjudged using virtual CT-bronchoscopy. It could
      also be useful as a screening examination method for patients with suspected
      endobronchial malignancy. Virtual hybrid bronchoscopy with a transparent color
      coded shaded-surface rendering model offers a useful alternative to fiberoptic
      bronchoscopy, and is particularly promising for patients for whom fiberoptic
      bronchoscopy is not feasible, contraindicated or refused.

PMID- 18317960
TI  - Electromagnetic navigation improves minimally invasive robot-assisted lung
      brachytherapy.
AB  - OBJECTIVE: Recent advances in minimally invasive thoracic surgery have renewed an
      interest in the role of interstitial brachytherapy for lung cancer. Our previous
      work has demonstrated that a minimally invasive robot-assisted (MIRA) lung
      brachytherapy system produced results that were equal to or better than those
      obtained with standard video-assisted thoracic surgery (VATS) and comparable to
      results with open surgery. The purpose of this project was to evaluate the
      performance of an integrated system for MIRA lung brachytherapy that incorporated
      modified electromagnetic navigation and ultrasound image guidance with robotic
      assistance. METHODS: The experimental test-bed consisted of a VATS box, ZEUS and
      AESOP surgical robotic arms, a seed injector, an ultrasound machine, video
      monitors, a computer, and an endoscope. Our previous custom-designed
      electromagnetic navigational software and the robotic controller were modified
      and incorporated into the MIRA III system to become the next-generation MIRA IV.
      Inactive brachytherapy seeds were injected as close as possible to a small metal
      ball target embedded in an opaque agar cube. The completion time, the number of
      attempts, and the accuracy of seed deployment were compared for manual placement,
      standard VATS, MIRA III, and the new MIRA IV system. RESULTS: The MIRA IV system
      significantly reduced the median procedure time by 61% (104 s to 41 s), tissue
      trauma by 75% (4 attempts to 1 attempt), and mean seed placement error by 64%
      (2.5 mm to 0.9 mm) when compared to a standard VATS. MIRA IV also reduced the
      mean procedure time by 48% (85 s to 44 s) and the seed placement error by 68%
      (2.8 mm to 0.9 mm) compared to the MIRA III system. CONCLUSIONS: A modified
      integrated system for performing minimally invasive robot-assisted lung
      brachytherapy was developed that incorporated electromagnetic navigation and an
      improved robotic controller. The MIRA IV system performed significantly better
      than standard VATS and better than MIRA III.

PMID- 18317961
TI  - Preoperative therapy as a model for translational research in breast cancer.

PMID- 18317962
TI  - OSM, LIF, its receptors, and its relationship with the malignance in human breast
      carcinoma (in situ and in infiltrative).
AB  - IL-6 cytokine family is composed by several members. IL-6, LIF, and gp130 have
      been associated with cancer progression. Cytokines play an important role in
      tumoral growth, invasion of the vessels and development of metastases.
      Immunoexpressions of LIF, OSM, LIFRbeta and OSMRbeta were studied in benign
      breast lesion, in situ and infiltrating tumors by Western blot and
      immunohistochemistry. Percentages of positive samples to OSM, LIF and OSMRbeta
      were higher in in situ carcinoma than in benign diseases and even higher in
      infiltrating tumors. gp130-positive samples was higher in infiltrating tumor than
      in benign diseases. All samples studied were LIFRbeta-positive. Infiltrating
      tumors showed the most intense immunostaining to LIFRbeta, OSM and OSMRbeta;
      comparing present results revealed an association between the expression of these
      proteins and increasing malignancy. In conclusions, development of breast tumor
      increases the expression of OSM, LIF, OSMRbeta, LIFRbeta and gp130, and this
      expression may be associated with the malignancy. IL-6 family exert their action
      through transducer receptor gp130, and gp130 expression increase with malignance,
      it might be a crucial point in the development of infiltrative adenocarcinoma.
      The secretion of OSM and LIF by both epithelial and stromal (paracrine manner)
      cells seems to promote tumor growth.

PMID- 18317963
TI  - Growth inhibition of insulin-like growth factor I receptor monoclonal antibody to
      human colorectal cancer cells.
AB  - AIM: Insulin-like growth factors (IGFs) and their receptors play a critical role
      in the growth and regulation of many type of malignant cells. The purpose of this
      study was to clarify the expression of Insulin-like growth factor I receptor (IGF
      IR) in a human colorectal cancer cell line HT-29 and investigate the effects of 2
      IGF-IR monoclonal antibodies (Mab) on the biological behavior of HT-29 cell line.
      METHODS: Immunohistochemistry was used to test the expression of IGF-IR in HT-29
      cell line, MTT assay was used to determine the antiproliferation effects of 2
      kinds of IGF-IR monoclonal antibody on HT-29 cells. The effects of apoptosis rate
      and cell cycle of HT-29 cells were estimated by flow cytometry (FCM). RESULTS:
      IGF-IR was expressed in the membranes of HT-29 cell line; MTT results show that
      each IGF-IR (alpha-Subunit)Ab-3 Mab group has remarkable difference (p < 0.01) as
      compared with control group, each IGF-IRalpha(1H7)L Mab group has no remarkable
      difference (p > 0.05) as compared with control group, each IGF-IRalpha(1H7)L Mab
      group has light antiproliferation effect on the HT-29 cells. IGF-IR(alpha
      Subunit)Ab-3 has stronger antiproliferation effect on the HT-29 cells and dose
      depended growth inhibition effects were observed when concentration is less than
      1.5 ug/ml;The 2 kinds of IGF-IR monoclonal antibody can arrest the cell cycle at
      any phase of HT-29 cells and induce apoptosis. Under the incubating conditions of
      containing 5 percent fetal bovine serum (FCS) and no FCS, the apoptosis
      percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L group have
      obviously increased (p < 0.01). After the number of cells was increased 30 times,
      the apoptosis percentage of IGF-IR(alpha-Subunit)Ab-3 group and IGF-IRalpha(1H7)L
      group have no remarkable differences as compared with control group (p > 0.05).
      CONCLUSIONS: Blockade of the IGF-IR with IGF-IR Mab inhibiting proliferation,
      arresting cell cycle and inducing apoptosis of HT-29 cells may represent a valid
      approach to inhibit tumor growth.

PMID- 18317964
TI  - Immune consequences of protracted host-tumor interactions in a transgenic mouse
      model of mammary carcinoma.
AB  - A transgenic mouse model of autochthonous mammary carcinoma was chosen to study
      the impact of tumor progression on the immune system over an extended period. We
      found: i) that splenocyte numbers, particularly myeloid cells, increased
      concurrently with tumor burden; ii) the percentage of tumor-infiltrating Treg
      cells was similar to that in human breast cancer; iii) suppressed T cell
      proliferation and cytokine production and; iv) significantly elevated MCP-1 and
      TNF-alpha in the sera of tumor-bearing mice. The modified immune status in these
      tumor-bearing hosts is consistent with a "syndrome" that likely impacts the
      efficacy of cancer immunosurveillance and response to therapy.

PMID- 18317965
TI  - Serum vascular endothelial growth factor (VEGF) levels correlate with tumor VEGF
      and p53 overexpression in endocrine positive primary breast cancer.
AB  - Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis,
      associated with unfavorable clinical characteristics in breast cancer. The aim of
      this study was to evaluate different angiogenic markers in endocrine-positive
      breast cancer patients. The authors analyzed serum and tumor samples from 71
      patients with endocrine-positive operable primary breast cancer to determine the
      expression and the possible relationship between circulating serum VEGF levels,
      tumor VEGF expression, microvessel density (MVD), and other immunohistochemical
      parameters. Basal VEGF serum levels were significantly higher in breast cancer
      patients than in healthy controls. A significant correlation was observed between
      basal VEGF serum concentrations, microvessel density (p = 0.01) and p53 status (p
      = 0.004). Intratumoral VEGF expression was significantly associated with
      neoplastic embolization (p = 0.041) and circulating VEGF levels (p = 0.047). The
      results confirm that in primary endocrine-positive breast cancer serum VEGF
      levels are elevated and show a positive relationship with tumor VEGF and p53
      overexpression.

PMID- 18317966
TI  - Circulating stromal cell derived factor-1alpha (SDF-1alpha) is predictive of
      distant metastasis in gastric carcinoma.
AB  - This study was conducted to investigate the value of the pretreatment circulating
      stromal cell derived factor-1alpha(SDF-1alpha) in patients with gastric
      carcinoma. We measured SDF-1alpha serum concentrations and evaluated the
      relationship between serum SDF-1alpha and serum vascular endothelial growth
      factor (VEGF) levels and clinical factors in 107 gastric cancer patients. Serum
      levels of SDF-1alpha and VEGF levels were higher in gastric cancer patients than
      in controls (p < 0.001). Serum SDF-1alpha levels were higher in metastatic
      patients than non-metastatic patients (p < 0.001). SDF-1alpha levels were
      correlated with the presence of distant metastases (r = 0.528; p < 0.001) and
      correlated with VEGF levels (r = 0.789; p < 0.001). SDF-1alpha might serve as a
      possible marker for predicting or monitoring distant metastasis in gastric
      carcinoma.

PMID- 18317967
TI  - Genomic instability in patients with non-small cell lung cancer assessed by the
      arbitrarily primed polymerase chain reaction.
AB  - In the present study, we used DNA profiling to measure genomic instability in 22
      patients with non-small cell lung cancer (NSCLC). Genomic instability was
      correlated with gender, the age of the patients at the time of diagnosis, the
      NSCLC subtype, histological grade and stage of the tumor, necrosis presence in
      the tumor and lymph node invasion. Genomic instability was significantly higher
      in patients older than 50 and those with adenocarcinoma compared to squamous-cell
      carcinoma. Most importantly, genomic instability significantly decreased as the
      tumor grade increased. Extensive genomic instability in the early carcinogenesis
      could be the prerequisite for NSCLC progression.

PMID- 18317968
TI  - A multicenter cohort study of dose-dense temozolomide (21 of 28 days) for the
      treatment of recurrent anaplastic astrocytoma or oligoastrocytoma.
AB  - Dose-dense temozolomide schedules deplete O6-methylguanine methyltransferase and
      may overcome chemoresistance. This multicenter cohort study enrolled 19 patients
      (15 anaplastic astrocytoma, 4 anaplastic oligoastrocytoma) who received
      temozolomide (100 mg/m2/day for 21 consecutive days every 28-day cycle) at first
      recurrence, either until disease progression or 12 cycles. Six-month progression
      free survival was 56%, comparing favorably with historic controls treated with
      the standard 5-day temozolomide schedule. Median survival was 12.9 months (95%
      CI: 3.7, 22 months). Among 15 evaluable patients, 2 had a complete or partial
      response, and 10 had stable disease. Grade 3 and 4 lymphopenia occurred in 53%
      and 47% of patients, respectively.

PMID- 18317969
TI  - The use of dynamic positron emission tomography imaging for evaluating the
      carcinogenic progression of intestinal metaplasia to esophageal adenocarcinoma.
AB  - BACKGROUND: In this study, we investigate the use of PET scanning in the
      carcinogenic progression of reflux esophagitis to Barrett's esophagus to high
      grade dysplasia to esophageal adenocarcinoma, and correlate the uptake levels of
      18F-FDG related to histological changes, and the rates of proliferation and
      apoptosis. METHODS: An established esophagoduodenal anastomsis rat model in
      conjunction with micro-PET scanning at 1 week, 1 month, 3 month, and 6 month
      after procedure was performed. RESULTS: Increased uptake levels of 18F-FDG were
      observed in the esophagi after EDA procedure. The higher level of 18F-FDG uptake
      within esophageal epithelium was identified in intestinal metaplastic
      transformation and esophagoduodenal adenocarcinoma by histological examination.
      CONCLUSIONS: Dynamic PET scanning represents a powerful tool in analyzing
      morphological carcinogenic transformation non-invasively in the esophagus. 18F-
      FDG accumulation was a sensitive marker in reflux esophageal injury carcinogenic
      progression from intestinal metaplasia to EAC.

PMID- 18317970
TI  - A pilot study of predictive markers of chemotherapy-related amenorrhea among
      premenopausal women with early stage breast cancer.
AB  - BACKGROUND: Premenopausal women treated for early stage breast cancer (ESBC) are
      at risk for chemotherapy-related amenorrhea (CRA). Prospectively-validated,
      predictive markers of CRA are needed. PATIENTS AND METHODS: Premenopausal women
      with ESBC and planned chemotherapy (>/= 25% risk of amenorrhea) were evaluated.
      Follicle stimulating hormone (FSH), estradiol, Inhibin A and B, anti-Mullerian
      hormone (AMH), and quality of life (QOL) were prospectively evaluated pre-, post
      , 6 months and 1 year post-chemotherapy and correlated with age and menstrual
      status. CRA was defined as absence of menses 1 year post-chemotherapy. RESULTS:
      Forty-four women were evaluated at the time of analysis. Median age at diagnosis
      and FSH 1 year post-chemotherapy were higher among women with CRA (44 yrs [33-51]
      vs. 40 yrs [31-43]; p = 0.03; 39.8 vs. 5.0 mLU/mL, p = 0.0058, respectively).
      Median estradiol 1 year post-chemotherapy was higher among women who resumed
      menses (108.3 vs. 41.3 pg/mL, p = 0.01). Pre-chemotherapy median Inhibin B and
      AMH were lower among women with CRA (33.2 vs. 108.8 pg/mL; p = 0.03; 0.16 vs.
      1.09 ng/mL, p = 0.02, respectively). The risk of CRA was increased among women
      with lower pre-chemotherapy Inhibin B (RR = 1.67, p = 0.15) and AMH (RR = 1.83, p
      = 0.05). Amongst women whose pre-chemotherapy Inhibin B and AMH values were below
      the median, the incidence of CRA was 87.5%. CONCLUSIONS: RESULTS indicate that
      pre-chemotherapy Inhibin B and AMH are lower among women experiencing CRA and may
      be predictive of CRA among premenopausal women facing chemotherapy for ESBC.

PMID- 18317971
TI  - Analysis of basement membrane structure and inflammation during the development
      of esophageal squamous cell carcinoma in the Chinese Chaoshan high risk region.
AB  - BACKGROUND & AIMS: To investigate relationships between basement membrane
      structure, inflammation, beta1 integrin expression, activation of ERK/MAPK
      signaling pathways, and cell proliferation in esophageal mucosa at various stages
      during the evolution of esophageal squamous cell carcinoma. METHODS: Three tissue
      arrays were made of 228 tissue cores from 428 surgically-resected specimens. The
      arrays included 26 samples of normal epithelium, 28 with hyperplasia, 18 with
      dysplasia, 27 with carcinoma in situ and 129 with invasive carcinoma. In
      addition, 21 cases of hyperplasia, 13 cases of dysplasia and 13 case of carcinoma
      in situ were obtained by manual microdissection of unfixed frozen tissue.
      Hematoxylin and eosin stained sections were used to evaluate the epithelium and
      inflammation. The periodic acid-Schiff stain and an immunohistochemical stain for
      laminin were used to examine the structure of basement membranes. The expression
      of beta1 integrin, p-ERK, and Ki67 were evaluated by quantitative
      immunohistochemistry. RT-PCR and Western blots were also used to detect
      expression of beta1 integrin. RESULTS: Quantitative scales were developed to
      classify basement membrane structure and inflammation. Basement membrane
      alterations correlated with the degree of epithelial change (chi2 = 501.9, p <
      0.01) and with the degree of lymphocytic infiltration in the lamina propria and
      epithelium (chi2 = 273.4, p < 0.01). There was a significant relationship between
      the extent of basement membrane alteration and the expression of beta1 integrin,
      p-ERK, and Ki67. CONCLUSIONS: The correlations suggest that there is a direct
      relationship between basement membrane structure and the development of
      esophageal squamous cell carcinoma.

PMID- 18317972
TI  - The role of environmental factors in the etiology of lymphoma.
AB  - The final quarter of the twentieth century saw a rise in the incidence of
      lymphoma, and it is now one of the most common neoplasms in the United States. As
      our understanding of lymphoma has grown, it has become clear that lymphomagenesis
      is a complex process and that many of the pathologic subtypes of lymphoma have
      different etiologies. This has prompted epidemiologists to investigate potential
      environmental causes of lymphoma. Below is a review of the body of literature
      that has resulted from these pursuits.

PMID- 18317973
TI  - The role of postoperative adjuvant chemotherapy following curative resection for
      gastric cancer: a meta-analysis.
AB  - To evaluate the effect of adjuvant chemotherapy on survival rates after curative
      resection of gastric cancer, MEDLINE (1969-2006), EMBASE (1974-2006),
      bibliographies, and review articles were searched for relevant articles. The meta
      analysis was finally based on 15 trials that included 3212 patients. RR for death
      in the treated group was 0.90 (95% CI, 0.84-0.96) (P = 0.0010). Little or no
      significant benefits were suggested in subgroup analyses between different
      population and regimens either. Postoperative adjuvant chemotherapy for gastric
      cancer confers slightly significant benefits compared to the surgery only group.
      The prognoses after surgery may differ among various population groups or because
      of different regimens.

PMID- 18317974
TI  - [Cough--assistance--ventilation: mechanical aids and assisted cough for patients
      with neuromuscular disease].

PMID- 18317975
TI  - [Physiology and pathophysiology of bronchial secretion].
AB  - The mechanisms of bronchial secretion are an important part of the innate defense
      system that protects the airways against pathogens and environmental toxins.
      Bronchial secretions are mainly produced by goblet cells and submucosal glands
      but also small amounts of surfactant from clara cells and some other fluids are
      part of the airway epithelium fluid. Together with the ciliary system the
      bronchial secretions are essential for the bronchial clearance ("mucociliary
      clearance"). Cilia beat within a periciliary layer with low viscosity ("sol
      phase"). They move the overlying mucous sheet ("gel-phase") by their tips towards
      the nose to remove those mucous particles together with foreign material and
      pathogens from the airways. The gel-layer of the airway epithelium fluid is
      formed mainly by water, mucins (MUC) and free proteins. Mucins are highly
      glycosylated macromolecules, to date more than 18 different MUC-genes have been
      described. In addition the airway epithelium fluids contains many antibacterial
      proteins and peptides including lysozyme, lactoferrin, secretory IgA, complement,
      beta-defensines as well as many others. Acute inflammatory or toxic stimuli can
      promote hypersecretion of mucins mediated by a large variety of cytokines and
      chemokines or even directly like some toxins. Chronic inflammatory conditions
      like asthma or COPD are associated with hyperplasia of goblet cells and
      submucosal glands thus increasing the secretory capacity of the airways. The
      system of mucociliary clearance forms a functional unit together with the
      coughing mechanisms discussed elsewhere in this journal.

PMID- 18317976
TI  - [Physiology and physiopathology of cough].
AB  - Cough clears off foreign bodies from the airways and maintains bronchial
      clearance when mucociliary transport is defective. Cough requires intact
      inspiratory muscles to inflate the lung up to 80 % of vital capacity and sound
      expiratory muscles to generate pressure against a closed glottis. Two mechanisms
      are required to facilitate proximal mucus transport: 1. Constriction of the
      cartilage containing airways caused by anterior bulging of the pars membranacea
      due to high air-flow velocity. 2. Thixotropia of the sputum. This feature changes
      mechanical properties in a way that sputum viscosity decreases with motion.
      Thixotropia is caused by the complex mucin-structure of the mucus.

PMID- 18317977
TI  - [Pathophysiology of respiratory muscle weakness].
AB  - The respiratory system consists of two parts which can be impaired independently
      from each other, the lungs and the respiratory pump. The latter is a complex
      system covering different anatomic structures: the breathing centre, the
      peripheral nervous system, the respiratory muscles, and the thorax. According to
      this complexity several underlying conditions can cause insufficiency of the
      respiratory pump, i. e. ventilatory failure. Disturbances of the breathing
      centre, different neuromuscular disorders, impairments of the mechanics, such as
      thoracic deformities or hyperinflation, and airway obstruction are example
      conditions responsible for ventilatory failure. Main characteristic of
      ventilatory failure is the occurrence of hypercapnia which is in contrast to
      pulmonary failure where diffusion disturbances typically not cause hypercapnia.
      Both acute and chronic ventilatory failure presenting with hypercapnia can
      develop. In acute ventilatory failure respiratory acidosis develops, but in
      chronic respiratory failure pH is normalized as a consequence of metabolic
      retention of bicarbonate. However, acute on chronic ventilatory failure can
      present with a combined picture, i. e. elevated bicarbonate levels, acidosis, and
      often severe hypercapnia. Clinical signs such as tachypnea, features of the
      underlying disease or hypercapnia are important diagnostic tools in addition to
      the measurement of pressures generated by the respiratory muscles. Non-invasive
      and widely available techniques, such as the assessment of the maximal ins- and
      expiratory mouth pressures (PImax, PEmax), should be used as screening
      instruments, but the reliability of these measurements is reduced due to the
      volitional character of the tests and due to the impossibility to define normal
      values. Inspiratory pressures can be assessed more accurately and independently
      from the patients' effort: with or without the insertion of oesophageal and
      gastric balloon catheters. However, this technique is more invasive and very
      complex. It is therefore restricted to centres with scientific aims.

PMID- 18317978
TI  - [Non-invasive ventilation: possibilities and limitations in patients with reduced
      ability to cough].
AB  - BACKGROUND: Neuromuscular diseases cover a wide range of pathologies, which are
      slowly or rapidly progressive. Besides the reduced capacity of the inspiratory
      muscles there is a limitation of expiration which compromises coughing.
      Ventilatory respiratory insufficiency (VRI) develops in stages, beginning during
      sleep with hypercapnia manifesting later on. Several retrospective studies have
      shown an improved alveolar ventilation, survival and quality of life for most
      NMD, even in non-bulbar ALS. The initiation of NIV is seen as apropriate when VRI
      in sleep develops. But patient acceptance to use NIV for more than 4 hours must
      be taken into account. NIV is limited by the interface which may cause skin
      abrasions or leakage due to pressure. NIV may be used day and night in stable
      conditions and with assistance experienced in mechanically-assisted coughing
      (MAC). The discussion of whether to perform tracheostomy remains a preeminent
      topic especially in ALS. CONCLUSION: NIV is effective in NMD and improves and
      prolongs life in slowly progressive NMD. Mask problems, leakage and bulbar
      dysfunction can limit the effectiveness. MAC is a tool that is very useful for
      elimination of bronchial secretions.

PMID- 18317979
TI  - [Assisted cough--physiotherapy to improve expectoration of mucus].
AB  - Pulmonary complications are the most common causes of mortality in patients with
      severe inspiratory and/or expiratory muscle weakness. An inspiratory tidal volume
      below 1500 ml and a peak cough flow below 160 L/min result in mucus retention and
      increase the risk of pneumonia. An intact cough function is pivotal for airway
      clearance during acute and chronic airway infections with increased mucus
      production as well as for protection against endotracheal aspirations. Effective
      cough requires that all of its phases work or are effectively supported. Non
      invasive assistance of inspiration can be provided by manual hyperinflation, air
      stacking, glossopharyngeal breathing or mechanical insufflation. Safe and
      effective methods of expiration assistance include manual thorax and abdominal
      compression, manual self-assistance as well as mechanical insufflation
      exsufflation. The use of these non-invasive inspiratory and expiratory muscle
      aids can decrease the risk of pulmonary complications in patients with severe
      ventilatory muscle weakness.

PMID- 18317980
TI  - [Basic principles of non-respiratory physiotherapy for neuromuscular diseases].
AB  - Loss of function, muscle pain and secondary muscoloskeletal complaints are common
      symptoms of patients with neuromuscular disease. Many patients develop a
      progressive handicap. Physiotherapeutic treatment is often used in the management
      of neuromuscular diseases. Different therapeutic strategies are useful depending
      on the stage and pathophysiology of the disease and with regard to the extent of
      the patient's handicap. The aims of the physiotherapy and realistic targets
      should be discussed critically with the patient at the beginning of the
      treatment. We propose different physiotherapeutic strategies depending on the
      stage of the underlying disease: 1) Patient is able to walk--active phase:
      education in self-training with regard to the risks of exhaustion. Manual and
      physical treatment of mycofascial complaints. 2) Progressive functional loss-
      assistive phase: support of compensation and daily functioning. 3) Patient in
      wheelchair or bedbound, loss of most voluntary functions--passive phase. The
      knowledge of the pathopysiology of the underlying disease is essential for the
      development of therapeutic strategies. Loss of upper neurons leads to the
      development of spasticity and muscle hypertonia whereas muscular atrophy and
      weakness is a prominent feature of lower motor neuron loss. Overtreatment and
      exhaustive training may lead to secondary muscle damage in primary myopathies.
      Training in short sessions with intervals between may have protective effects.

PMID- 18317981
TI  - [Oscillating physiotherapy for secretolysis].
AB  - Assisted coughing and mechanical cough aids compensate for the weak cough flow in
      patients with neuromuscular diseases (NMD). In cases with preserved respiratory
      muscles also breathing techniques and special devices, e. g., flutter or acapella
      can be used for secretion mobilisation during infections of the airways. These
      means are summarised as oscillating physiotherapy. Their mechanisms are believed
      to depend on separation of the mucus from the bronchial wall by vibration, thus
      facilitating mucus transport from the peripheral to the central airways. In
      mucoviscidosis and chronic obstructive pulmonary disease their application is
      established, but there is a paucity of data regarding the commitment in patients
      with neuromuscular diseases. The effective adoption of simple oscillation
      physiotherapeutic interventions demands usually a sufficient force of the
      respiratory muscles--exceptions are the application of the percussionaire
      (intrapulmonary percussive ventilator, IPV) or high frequency chest wall
      oscillation (HFCWO). In daily practice there is evidence that patients with weak
      respiratory muscles are overstrained with the use of these physiotherapeutic
      means, or get exhausted. A general recommendation for the adoption of simple
      oscillating physiotherapeutic interventions cannot be made in patients with NMDs.
      Perhaps in the future devices such as IPV or HFCWO will prove to be more
      effective in NMD patients.

PMID- 18317982
TI  - [Diagnosis and treatment of dysphagia in patients with neuromuscular disease].
AB  - Dysphagia is a risk factor for pneumonia in patients with neuromuscular disease
      (NMD). The management of dysphagia influences respiratory complications and
      prognosis in NMD. Early symptoms of dysphagia are often discrete. There may be
      symptoms like change of voice ("wet voice") or dyspnea following a meal, or
      weight loss. Fiberoptic flexible endoscopic evaluation of swallowing (FEES) and
      videofluoroscopy are important diagnostic tools in the work-up of dysphagia. FEES
      should be performed with different nourishments like fluid (water), pulp, normal
      meal and dry cookies. The therapy for swallowing dysfunction in patients with NMD
      should be performed by experienced speech therapists in an interdisciplinary
      setting with regard to the fatiguability of the orophyryngeal muscles. Therapy
      should focus on adaptive procedures and safe, adapted nourishment.

PMID- 18317983
TI  - [Treatment of sialorrhea in patients under long-term ventilation].
AB  - Sialorrhea (drooling or excessive salivation) is a common problem in patients
      with progressive neurolomuscular diseases and bulbar palsy. Contributing factors
      are hypersecretion of saliva induced by cholinergic drugs and poor dental status.
      Non-invasive ventilation is often severely impaired in these patients. Treatment
      should be initiated with a thorough evaluation of the medication and of the oral
      status by an otorhinolaryngologist. As drooling is commonly caused by poor oral
      or pharyngeal neuromuscular control, swallowing therapy should be initiated by a
      speech therapist. Further treatment options are anticholinergic medications,
      botulinum toxin injections into the salivary gland, radiation and and surgical
      procedures. Whereas systemic anticholinergic medications lead often to side
      effects, the (ultrasound-guided) injection of botulinum toxin into the parotid
      and submandibular gland is a safe and effective method for controlling drooling
      for at least 2 months.

PMID- 18317984
TI  - [Management of secretion in patients with neuromuscular diseases].
AB  - BACKGROUND: Many patients with neuromuscular diseases suffer from a weak cough.
      Due to infection or aspiration a life-threatening situation may occur. There are
      different options for the therapists to improve secretion clearance from the
      airways in the patient with a weak cough. Furthermore, there are indications that
      consequent practice of techniques to ameliorate bronchial clearance may also
      improve the prognosis of patients with neuromuscular diseases. MANAGEMENT: The
      management of secretions in neuromuscular disorders does not consist of single
      actions but is rather a complex programme. Diagnostics and several therapeutic
      measures have to be performed intensely and regularly. The diagnosis of a weak
      cough flow is based on anamnestic data, e. g., increase in secretions or
      dysphagia, physical examination, e. g., paradoxical breathing, and easily
      measured lung function parameters like vital capacity and peak cough flow (PCF).
      The diagnosis of an accumulation of secretions in the airways can be made easily
      by means of a pulse oximetry: while breathing room air the oxygen saturation in
      the case of a healthy lung and clean airways will be better than 95 %. A decline
      can, among others, be induced by amounts of secretions in the airways. The
      consequence should be measures to improve secretion expectoration (so-called
      oximetry-feedback protocol). To assist in secretion elimination from the airways
      several means are available like air stacking, manually assisted cough and
      mechanical assisted coughing--e. g., mechanical insufflator-exsufflator. Which of
      these techniques should be used depends on the extent of the disease: with
      preserved facial and bulbar muscles, air stacking alone or in combination with
      manually assisted coughing may be adequate and effective in the home care of the
      patient. In case of failure of these means, e. g., in bulbar paralysis, there is
      the possibility to apply mechanically assisted coughing by means of the
      mechanical insufflator-exsufflator. In case of tracheostomy, air stacking or
      mechanical assisted coughing has to be combined with tracheal suctioning. Acute
      infections of the lower airways are a special challenge: personnel intensive
      application of a combination of different secretion eliminating techniques, e.
      g., bronchoscopy in the hospital, manually assisted coughing and mechanically
      assisted coughing have to be performed in high intensity to avoid intubation.
      CONCLUSION: The early diagnosis of a weak cough in NMD patients is important for
      the timely start of existing and effective measures for improving the capacity of
      elimination of secretions--air stacking, manually assisted cough and mechanically
      assisted cough. Although there is no high degree of evidence, we believe that
      morbidity and possibly mortality can be affected in a positive manner.

PMID- 18317985
TI  - [Technical aspects of mechanical insufflator-exsufflators. Construction and
      function of the Emerson CoughAssist].
AB  - The electromechanical insufflator-exsufflator (Emerson CoughAssist) was developed
      as an aid for patients with neuromuscular disorders suffering from impaired
      cough. The insufflator-exsufflator simulates and supports physiological cough by
      supporting inspiration with positive pressure and shifting this positive pressure
      rapidly into a negative pressure that supports exsufflation and thus bronchial
      clearance. Maximum pressures are +/- 60 cm H2O, pressures between 30 and 50 cm
      H2O are sufficient to produce assisted cough in adults with neuromuscular
      disease. The pressure shift from positive to negative occurs with 0.02 sec and is
      regulated by a magnetic valve. An anaesthetic facemask is used as interface,
      alternatively, a mouthpiece can be used in combination with a nose strap. It is
      also possible to use the insufflator-exsufflator in patients with tracheostomy.
      We present in this article detailed information about the technical principles
      and practical use of the electromechanical insufflator-exsufflator.

PMID- 18317986
TI  - [NIV--modes and prognosis].
AB  - Non-invasive (NIV) as well as invasive mechanical ventilation are established for
      the treatment of ventilatory failure in neuromuscular diseases. The EUROVENT
      study provides data about mechanical ventilation at home. In this survey there is
      a trend towards pressure-derived ventilation in these patient groups. Volume
      cycled ventilators had been used in 41% patients with neuromuscular diseases.
      During the past decade a remarkable change towards pressure-cycled ventilation
      has occurred. Two recently published, randomised cross-over studies demonstrated
      equal efficacy of volume-cycled ventilation compared to pressure-cycled
      ventilation in terms of gas exchange and sleep efficacy in chronic ventilatory
      failure. In both groups the median survival times were equal. In respiratory
      muscle failure, assisted ventilation, assist/controlled ventilation as well as
      controlled ventilation are applied. Between 1977 and 2001, long-term survival
      improved in patients with Duchenne muscular dystrophy (DMD) in Denmark based on a
      strict organisation of care, home ventilation as standard treatment and the
      establishment of centres for home ventilation. The proportion of ventilated
      patients rose from 0.9% to 43.4% of all DMD patients. The median survival of an
      untreated DMD patient is 9.7 months. Simonds demonstrated a 5-year survival rate
      of 73% in these groups of patients under home mechanical ventilation. In patients
      with the more rapidly deteriorating amyotrophic lateral sclerosis, the efficacy
      of home ventilation is less impressive and bulbar involvement serves as an
      independent negative predictor.

PMID- 18317988
TI  - Sensitive and specific LC-MS assay for quantification of digoxin in human plasma
      and urine.
AB  - Digoxin, a commonly prescribed cardiac glycoside with a narrow therapeutic
      window, is routinely used in pharmacokinetic studies to assess the in vivo
      activity of the drug efflux pump P-glycoprotein. To minimize adverse events, a
      sub-therapeutic dose of digoxin is usually administered, producing low plasma
      concentrations requiring a sensitive detection technique. Commonly available
      immunoassay techniques do not provide the required sensitivity to measure these
      low plasma concentrations and are potentially non-specific in certain subject
      populations. Previously published mass spectrometric techniques require either
      large plasma volumes or a tandem mass spectrometer. To overcome these challenges
      we have developed a sensitive and specific LC-MS method for the quantification of
      digoxin in small volumes of human plasma and urine. Plasma (1 mL) was extracted
      with methyl t-butyl ether under basic conditions followed by LC-MS detection of
      the sodium adducts of digoxin (803.4 m/z) and digitoxin (787.4 m/z, internal
      standard). Linearity and accuracy were demonstrated across a wide range of
      digoxin plasma concentration (0.05-1.5 ng/mL). This specific, sensitive,
      validated digoxin LC-MS assay can be used to quantify sub-therapeutic digoxin
      plasma concentrations in men and women (pregnant and non-pregnant).

PMID- 18317989
TI  - New applications of cyclodextrins in electrically driven chromatographic systems:
      a review.
AB  - The new achievements in the employment of native and derivatised cyclodextrins in
      various electrically driven chromatographic systems are compiled. Cyclodextrin
      assisted separation techniques are concisely described and critically evaluated
      with special emphasis on the separation of enantiomer pairs.

PMID- 18317990
TI  - Personal control after a breast cancer diagnosis: stability and adaptive value.
AB  - OBJECTIVE: This longitudinal study aims to gain more insight in both the changes
      in personal control due to a breast cancer diagnosis, as well as in the stress
      buffering effect of personal control. METHODS: Personal control and distress were
      assessed in breast cancer patients not treated with chemotherapy (n=47), breast
      cancer patients treated with chemotherapy (n=32) and in healthy women (n=58) at
      3, 9 and 15 months after diagnosis. RESULTS: Results indicate that personal
      control was affected only in patients treated with chemotherapy, particularly
      right after the completion of treatment. Furthermore, the cross-sectional and
      longitudinal results provide modest support for the stress-buffering potential of
      control. CONCLUSIONS: The findings and future directions of research on the role
      of personal control in the adjustment to cancer will be discussed.

PMID- 18317991
TI  - End-of-life care in Italy: personal experience of family caregivers. A content
      analysis of open questions from the Italian Survey of the Dying of Cancer
      (ISDOC).
AB  - OBJECTIVE: This study aims at describing the emotional and practical experience
      of a representative sample of Italian non-professional caregivers when caring for
      a terminally ill family member and is part of the 'Italian Survey of the Dying of
      Cancer', which involved 2000 adult cancer deaths representative of the whole
      country. METHODS: Information on patients' experience was gathered from non
      professional caregivers by an interview. A specific question was asked about the
      caregivers' emotional and practical experiences while assisting a terminally ill
      relative. A content analysis of the open question on caregivers' perceptions was
      performed on transcribed answers. Three researchers independently generated
      categories. Subsequently, areas where they differed were reconsidered and an
      interpretation was agreed upon. RESULTS: Valid interviews were obtained from 1231
      non-professional caregivers. Answers were classified according to the perception
      of the experience as positive (33.1%), negative (65.1%) or neutral (1.8%).
      CONCLUSION: Assisting a family member with cancer in his/her last three months of
      life is a very strong physical and mental stress for the caregiver. In some
      cases, this experience is nevertheless perceived as an evolution chance. Health
      care providers should need to develop programs to ensure that family caregivers'
      needs for information and support are given great importance.

PMID- 18317994
TI  - To vaccinate or to screen--is that the question?
AB  - The recent recommendation by the Joint Committee on Vaccination and Immunisation
      (JCVI) that the human papillomavirus (HPV) vaccine should be routinely given to
      girls aged 12-13 raises important questions about prevention programmes to combat
      cervical cancer in the UK. The proposal of a mass immunization programme against
      HPV also presents some important ethical dilemmas. This paper discusses these
      questions within the current context of cervical cancer prevention programmes
      considering issues of efficacy and the impact of immunization on women and the
      implications for the current cervical screening programme. We argue that despite
      the JCVI recommendation to implement a national vaccination programme in the UK,
      which will undoubtedly save lives, further consideration needs to be given to key
      concerns about the efficacy of the delivery programme and potential risks
      associated with this, the additional costs of delivery of such a programme, the
      challenge of ensuring continued vaccination coverage among the highest risk
      population, the goals of the vaccination programme and the need to continue
      cervical cancer screening despite a vaccination programme.

PMID- 18317997
TI  - Increased nuchal translucency and foetal aortic incompetence due to a dysplastic
      bicuspid valve.

PMID- 18317998
TI  - First-trimester maternal serum progesterone in aneuploid pregnancies.
AB  - BACKGROUND: First-trimester maternal serum screening for Down syndrome (DS) can
      be improved by the use of additional serum markers. We examined whether
      progesterone (P), synthesized by placenta, might be a first-trimester maternal
      serum marker for fetal DS. MATERIALS AND METHODS: P was quantified in first
      trimester maternal serum from 42 DS, six trisomy 18 and two trisomy 13
      pregnancies and 115 controls. Log-regression of P versus gestational age in days
      was used to convert P concentrations into multiples of the median (MoM). RESULTS:
      The P concentrations in controls increased with gestational age (p = 9.5 x 10(
      7)). The log10MoM P distribution in DS pregnancies was not significantly
      different from that in controls. However, from day 58-67, the log10MoM P was
      elevated in DS pregnancies (n = 10) with a mean (SD) of 0.1040 (0.0956), compared
      to a mean (SD) of - 0.0109 (0.1661) in controls (n = 24) (p = 0.05). Five out of
      six trisomy 18 and both trisomy 13 pregnancies had a P MoM < 1. CONCLUSION: P is
      not a useful marker for DS in first trimester, except perhaps in a narrow
      gestational age window from day 58 to 67. P is a trisomy 18/13 marker.

PMID- 18317999
TI  - Decreased plasma levels of metastin in early pregnancy are associated with small
      for gestational age neonates.
AB  - OBJECTIVE: To investigate whether pregnancies with small for gestational age
      (SGA) neonates, defined as customized birth weight below the 10th centile, are
      associated with altered levels of metastin in maternal plasma in the first
      trimester. STUDY DESIGN: Maternal blood was obtained between 8 and 14 weeks of
      pregnancy. Levels of metastin were measured in pregnancies with (n = 31) or
      without SGA-neonates (n = 31), matched for gestational age at venipuncture.
      Measurement of beta-hCG was included to study the influence of gestational age
      and placental volume on plasma levels of the measured markers. RESULTS: Metastin
      was significantly lower in SGA-pregnancies compared to an equal number of matched
      uneventful pregnancies (metastin: 1376 +/- 1317 pmol/L vs 2035 +/- 1260 pmol/L, p
      = 0.035; mean +/- standard deviation). beta-hCG levels were not different.
      CONCLUSION: Metastin is significantly lower in maternal plasma in the first
      trimester, in pregnancies with SGA-neonates. It might therefore be used in
      combination with other markers for risk estimation of growth impairment in the
      first trimester.

PMID- 18318000
TI  - First trimester screening for Down syndrome in rhesus negative women.
AB  - OBJECTIVES: To explore the effect of maternal rhesus status on first-trimester
      screening markers for Down syndrome. METHODS: We accessed a database of singleton
      pregnancies undergoing first-trimester genetic screen with maternal Rh status
      documented and pregnancy outcome information available. Excluded were cases of
      fetal chromosomal or structural abnormalities, or maternal systemic disease.
      Results of maternal serum pregnancy-associated plasma protein A (PAPP-A) and beta
      human chorionic gonadotrophin (beta-hCG) adjusted for gestational age were
      compared between Rh-negative and Rh-positive women with p < 0.05 considered
      significant. RESULTS: Two thousand two hundred and two pregnancies fulfilled the
      study criteria, and 160 of them (7%) were Rh negative. Only free beta-hCG
      corrected multiples of the median (MoM) values were statistically increased in Rh
      negative women (p < 0.009). Using a cut-off of 1:300, screen-positive rates of
      maternal serum biochemistry were not significantly different between Rh-negative
      and Rh-positive women (12.5 vs 10.4%, p = 0.41). CONCLUSION: The present study
      focused on measurements of beta-hCG and PAPP-A in the sera of women with Rh
      negative blood group. Women with Rh-negative blood type have similar first
      trimester serum PAPP-A MoM values as Rh-positive women, but significantly higher
      beta-hCG MoM values. However, there was no significant difference in the screen
      positive rate for Down syndrome between the two groups.

PMID- 18318001
TI  - Developing a self-rating measure of patient competence in the context of
      oncology: a multi-center study.
AB  - OBJECTIVE: Concepts of patient competence (PC) are being increasingly used, but
      seldom clearly defined in the context of shared medical treatment decision making
      and coping with cancer. The meaning of such concepts should therefore be
      clarified, and measures developed that permit the assessment of different facets
      of this patient characteristic. Consequently, this study attempted to contribute
      to the definition and measurement of PC. METHODS: Employing literature reviews
      and qualitative interviews, we developed a working definition of PC in the
      context of cancer from which we designed a self-rating measure of this patient
      characteristic that was then tested for validity and reliability in a sample of
      N=536 patients with cancer. RESULTS: Using factor analyses, we developed five
      problem- and three emotion-focused subscales that measure distinct facets of PC
      with satisfactory reliability. Additional analyses provide preliminary evidence
      of the instruments' validity. CONCLUSIONS: This study represents an essential
      first step in developing a reliable self-rating measure of PC in the context of
      cancer. Although further refinement of this measure is clearly required, it
      provides a preliminary methodological basis for empirically investigating the
      determinants and potential health effects of PC.

PMID- 18318002
TI  - Serum proteomic analysis during nicotine self-administration, extinction and
      relapse in rats.
AB  - Nicotine dependence is known to induce long-term neural adaptations in brain. The
      purpose of this study was to verify whether specific protein patterns related to
      nicotine self-administration states could also be detected in a peripheral
      tissue. A serum proteomic analysis was performed by 2-DE on samples taken at six
      time points: N, naive; P, priming; S, self-administration; W, withdrawal; E,
      extinction; R, relapse. After image analysis, spot volume values were submitted
      to a principal component analysis and relevant comparisons were selected. In N
      versus S; S versus W; E versus R; S versus R and S versus E comparisons a clear
      separation between groups could be observed, suggesting that each self
      administration state correlates with a specific protein expression pattern.
      Partial least squares discriminant analysis was adopted to rank proteins by the
      contribution to the overall separation. A number of spots were identified; among
      them, C reactive protein and haemopexin displayed a significant reduction after
      nicotine administration; two haemopexin isoforms were decreased in the S state
      and antithrombin III was increased in the E phase. This study showed that
      specific protein patterns related to the nicotine self-administration states
      exist in serum. Further development of this approach may provide biomarkers to
      assess dependence states of drug-taking individuals.

PMID- 18318003
TI  - Capillary electrophoresis for the detection of PMP22 gene duplication: study in
      Mexican patients.
AB  - Charcot-Marie-Tooth (CMT) disease is the most common inherited disorder of the
      human peripheral nerve, with an estimated overall prevalence of 17-40/10 000 [1].
      The typical phenotype presents peroneal muscular atrophy and pes cavus [2]. CMT
      is usually divided into two large types, about two-thirds of the patients have
      CMT type 1 (CMT1), that affects the layer of myelin (demyelination). In type 2
      (CMT2) the nerve fibers are affected (axonal). CMT diseases have autosomal
      dominant, autosomal recessive, and X-linked inheritance [1]. The most frequent
      subtype is 1A (CMT1A) with autosomal dominant transmission, secondary in most
      cases to a tandem duplication of a 1.5 Mb DNA fragment on chromosome 17p11.2-p12
      [4-7]. In this region, the codification of the peripheral myelin protein 22
      (PMP22) takes place. The severity of the disease varies among patients, even
      within the same family, from almost no symptoms to severe foot-drop and sensory
      loss. The PMP22 gene has four exons and is regulated by two promoters located
      toward the extreme 5'. The origin of the duplication that causes the disease is
      an uneven exchange of the chromatids during the meiosis. This unequal
      recombination occurs between two regions that limit the PMP22 gene, described as
      REP places of 24 kb, proximal and distal [3, 4].

PMID- 18318004
TI  - Enantiomeric separations of binaphthyl derivatives by capillary electrophoresis
      using N-(2-hydroxydodecyl)-L-threonine as chiral selector: effect of organic
      additives.
AB  - The chiral selectivity of a novel amphiphile, N-(2-hydroxydodecyl)-L-threonine (2
      HDT), was evaluated for enantiomeric resolution of three binaphthyl derivatives
      (+/-)-1,1'-bi-2-naphthol, (+/-)-1,1'-binaphthyl-2,2'-diamine, and (+/-)-1,1'
      binaphthyl-2,2'-diylhdrogen phosphate (BNP) by micellar EKC. The effects of three
      organic modifiers, methanol, isopropanol, and acetonitrile, on the separations of
      enantiomers of these compounds were investigated. Separation of enantiomers could
      be achieved in relatively dilute solutions of the pure surfactant. However, best
      separations of enantiomers were obtained only in the presence of 10% v/v
      acetonitrile. Enantiomeric impurity in nonracemic mixtures of R- and S-forms of
      BNP was determined.

PMID- 18318005
TI  - Packaging of microfluidic chips via interstitial bonding technique.
AB  - In this paper, we describe an interstitial bonding technique for packaging of
      microfluidic chips. The cover plate is first placed on top of the microfluidic
      chip, followed by dispensing the UV-curable resin into the resin-loading
      reservoirs. With the interstitial space between the cover plate and the
      microfluidic chip connecting to the loading reservoirs, the UV-curable resin
      wicks through capillary force action and hydrostatic pressure generated by the
      liquid level in the resin-loading reservoirs. When reaching the microchannels,
      the UV-curable resin stops flowing into the microchannels due to the force
      balance between the surface tension and hydrostatic pressure. The assembly is
      then placed under the UV light, followed by further curing in the thermal oven.
      It is found that there is no leakage from the bonded microfluidic chips and a
      good DNA separation result was obtained by using the microfluidic chips as
      fabricated. This bonding technique is relatively simple and fast, which can be
      applied to the packaging of microfluidic chips made from hybrid materials with
      complicated designs as long as the interstitial space connects to the loading
      reservoirs.

PMID- 18318006
TI  - Proteome analysis of aflatoxin B1-induced hepatocarcinogenesis in tree shrew
      (Tupaia belangeri chinensis) and functional identification of candidate protein
      peroxiredoxin II.
AB  - In order to explore the proteins responsible for hepatocellular carcinoma (HCC),
      aflatoxin B(1)-induced hepatocarcinogenesis in tree shrew (Tupaia belangeri
      chinensis) was analyzed with 2-DE and MS. By comparing HCC samples with their own
      precancerous biopsies and HCC-surrounding tissues, a group of candidate proteins
      that differentially expressed in HCC were obtained. Peroxiredoxin (Prx) II, one
      of the candidates with distinct alteration, was further investigated and
      validated. Western blot and RT-PCR assays confirmed the overexpression of Prx II
      in both tree shrew and human HCC tissues. RNA interference for silencing Prx II
      was employed subsequently to explore the function and underlying mechanism of Prx
      II on liver cancer cell line Hep3B. Results showed the cell proliferation and
      clone formation decreased obviously when Prx II expression was inhibited, while
      the flow cytometer analysis showed the percentage of cell apoptosis enhanced.
      Inhibition of Prx II expression also obviously increased the generation of ROS
      and malondialdehyde, both are the products from peroxidation. These results imply
      the important role of Prx II in hepatocarcinogenesis, possibly through its
      function in regulating peroxidation and hereby to provide a favorable
      microenvironment for cancer cell surviving and progressing.

PMID- 18318007
TI  - Comparative glycomics of connective tissue glycosaminoglycans.
AB  - Homeostasis of connective joint tissues depends on the maintenance of an
      extracellular matrix, consisting of an integrated assembly of collagens,
      glycoproteins, proteoglycans, and glycosaminoglycans (GAGs). Isomeric chondroitin
      sulfate (CS) glycoforms differing in position and degree of sulfation and uronic
      acid epimerization play specific and distinct functional roles during development
      and disease onset. This work profiles the CS epitopes expressed by different
      joint tissues as a function of age and osteoarthritis. GAGs were extracted from
      joint tissues (cartilage, tendon, ligment, muscle, and synovium) and partially
      depolymerized using chondroitinase enzymes. The oligosaccharide products were
      differentially stable isotope labeled by reductive amination using 2-anthranilic
      acid-d(0) or -d(4) and subjected to amide-hydrophilic interaction chromatography
      (HILIC) online LC-MS/MS. The analysis presented herein enables simultaneous
      profiling of the expression of nonreducing end, linker region, and Delta
      unsaturated interior oligosaccharide domains of the CS chains among the different
      joint tissues. The results provide important new information on the changes to
      the expression of CS GAG chains during disease and development.

PMID- 18318008
TI  - Large-scale phosphoproteome analysis of human liver tissue by enrichment and
      fractionation of phosphopeptides with strong anion exchange chromatography.
AB  - The mixture of phosphopeptides enriched from proteome samples are very complex.
      To reduce the complexity it is necessary to fractionate the phosphopeptides.
      However, conventional enrichment methods typically only enrich phosphopeptides
      but not fractionate phosphopeptides. In this study, the application of strong
      anion exchange (SAX) chromatography for enrichment and fractionation of
      phosphopeptides was presented. It was found that phosphopeptides were highly
      enriched by SAX and majority of unmodified peptides did not bind onto SAX.
      Compared with Fe(3+) immobilized metal affinity chromatography (Fe(3+)-IMAC),
      almost double phosphopeptides were identified from the same sample when only one
      fraction was generated by SAX. SAX and Fe(3+)-IMAC showed the complementarity in
      enrichment and identification of phosphopeptides. It was also demonstrated that
      SAX have the ability to fractionate phosphopeptides under gradient elution based
      on their different interaction with SAX adsorbent. SAX was further applied to
      enrich and fractionate phosphopeptides in tryptic digest of proteins extracted
      from human liver tissue adjacent to tumorous region for phosphoproteome
      profiling. This resulted in the highly confident identification of 274
      phosphorylation sites from 305 unique phosphopeptides corresponding to 168
      proteins at false discovery rate (FDR) of 0.96%.

PMID- 18318009
TI  - Improved recovery of proteome-informative, protein N-terminal peptides by
      combined fractional diagonal chromatography (COFRADIC).
AB  - We previously described a proteome-wide, peptide-centric procedure for sorting
      protein N-terminal peptides and used these peptides as readouts for protease
      degradome and xenoproteome studies. This procedure is part of a repertoire of gel
      free techniques known as COmbined FRActional DIagonal Chromatography (COFRADIC)
      and highly enriches for alpha-amino-blocked peptides, including alpha-amino
      acetylated protein N-terminal peptides. Here, we introduce two additional steps
      that significantly increase the fraction of such proteome-informative, N-terminal
      peptides: strong cation exchange (SCX) segregation of alpha-amino-blocked and
      alpha-amino-free peptides and an enzymatic step liberating pyroglutamyl peptides
      for 2,4,6-trinitrobenzenesulphonic acid (TNBS) modification and thus COFRADIC
      sorting. The SCX step reduces the complexity of the analyte mixture by enriching
      N-terminal peptides and depleting alpha-amino-free internal peptides as well as
      proline-starting peptides prior to COFRADIC. The action of pyroglutamyl
      aminopeptidases prior to the first COFRADIC peptide separation results in greatly
      diminishing numbers of contaminating pyroglutamyl peptides in peptide maps. We
      further show that now close to 95% of all COFRADIC-sorted peptides are alpha
      amino-acetylated and, using the same amount of starting material, our novel
      procedure leads to an increased number of protein identifications.

PMID- 18318010
TI  - 6th HUPO Annual World Congress - Proteomics Standards Initiative Workshop 6-10
      October 2007, Seoul, Korea.
AB  - The plenary session of the Proteomics Standards Initiative of the Human Proteome
      Organisation at the 6th annual HUPO world congress updated the delegates on the
      current status of the ongoing work of this group. The new MS interchange format,
      mzML, had been entered into the HUPO document process immediately prior to the
      meeting and was already under active discussion by prospective users. It is
      anticipated this will become the de facto standard in this area in 2008. Minimal
      requirements documents are in the process of being published and proteomics
      journals are beginning to request data deposition as part of the manuscript
      submission process. The session ended with a lively debate on the practical
      implications these advances will have on daily laboratory work, on submission
      procedures and the tools which are being developed to assist in these activities.

PMID- 18318011
TI  - Proteomics Data Collection - 2nd ProDaC Workshop 5 October 2007, Seoul, Korea.
AB  - Proteomics Data Collection (ProDaC) is an EU-funded "Coordination Action" within
      the 6th framework programme. It aims to simplify the publication, dissemination
      and utilization of proteomics data by establishing standards that will support
      broad data collection from the research community. As a part of ProDaC, regular
      workshops are organized on a half-yearly basis to enable communication and
      discussion of the involved partners and to report on project progress. After the
      kick-off meeting (October 2006) in Long Beach, CA, USA and the 1st workshop in
      Lyon, France (April 2007), the 2nd ProDaC workshop took place at the COEX
      InterContinental Hotel in Seoul, Korea, on 5th October 2007, shortly before the
      HUPO World Congress. The progress achieved within the first year was presented by
      the leaders of the work packages. Additionally, a Journal's representative talked
      about his experiences and future plans concerning Proteomics standards; and two
      further external speakers presented their research related to data handling and
      Proteomics repositories.

PMID- 18318012
TI  - Development of a 6-hydroxychroman-based derivatization reagent: application to
      the analysis of 5-hydroxytryptamine and catecholamines by using high-performance
      liquid chromatography with electrochemical detection.
AB  - We developed a novel derivatization reagent, (2R)-2,5-dioxopyrrolidin-1-yl
      2,5,7,8-tetramethyl-6-(tetrahydro-2H-pyran-2-yloxy)chroman-2-carboxylate (NPCA),
      for electrochemical (EC) detection in HPLC. NPCA was synthesized from (R)-(+)-6
      hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (alpha-CA), which exhibits
      intense EC response. NPCA successfully yielded alpha-CA derivatives of primary
      amines by a two-step derivatization procedure. Following pre-column
      derivatization with NPCA, a simultaneous determination of alpha-CA derivatives of
      neuroactive monoamines [dopamine (DA), epinephrine, and 5-hydroxytryptamine (5
      HT)], their monoamine oxidase metabolites (3,4-dihydroxyphenylacetic acid,
      homovanillic acid, and 5-hydroxyindole-3-acetic acid) and their catechol-O
      methyltransferase metabolites [3-methoxytyramine (3-MT) and normetanephrine
      (NMN)] was completely achieved using our HPLC-EC method. Using an HPLC equipped
      with coulometric electrode-array detection system, the resultant alpha-CA
      derivatives of NMN, 5-HT, DA and 3-MT showed intense EC responses, that were
      approximately 1.3, 1.4, 1.1 and 1.4-fold higher than the corresponding native
      forms, respectively. The detection limits were in the range of approximately 16
      60 fmol on column (signal-to-noise ratio 3). The proposed HPLC method was applied
      to determine 5-HIAA, HVA, alpha-CA-5-HT and alpha-CA-DA in rat urine. As a
      consequence, these analytes were successfully determined with satisfactory
      precisions.

PMID- 18318013
TI  - Simultaneous determination of beta-blockers in human plasma using liquid
      chromatography-tandem mass spectrometry.
AB  - A detailed procedure for the analysis of four beta-blockers, acebutolol,
      labetalol, metoprolol and propranolol, in human plasma by high-performance liquid
      chromatography (LC)-tandem mass spectrometry (MS-MS) using an MSpak GF column,
      which enables direct injection of crude plasma samples, is presented. Protein
      and/or macromolecule matrix compounds were eluted first from the column, while
      the drugs were retained on the polymer stationary phase of the MSpak GF column.
      The analytes retained on the column were then eluted into an acetonitrile-rich
      mobile phase using a gradient separation technique. All drugs showed base peak
      ions due to [M + H]+ ions by LC-MS with positive ion electrospray ionization, and
      the product ions were produced from each [M + H]+ ion by LC-MS-MS. Quantification
      was performed by selected reaction monitoring. The recoveries of the four beta
      blockers spiked into plasma were 73.5-89.9%. The regression equations for all
      compounds showed excellent linearity in the range 10-1000 ng/mL of plasma, with
      the exception of propranolol (10-800 ng/mL). The limits of detection and
      quantification for each drug were 1-3 and 10 ng/mL, respectively, of plasma. The
      intra- and inter-day coefficients of variation for all drugs in plasma were not
      greater than 10.9%.

PMID- 18318015
TI  - Determination and pharmacokinetic study of nodakenin in rat plasma by RP-HPLC
      method.
AB  - A simple, sensitive and selective RP-HPLC method has been developed for
      quantification of nodakenin in rat plasma. Nodakenin in rat plasma was extracted
      with acetonitrile, which also acted as a deproteinization agent. Chromatographic
      separation of nodakenin was performed on an analytical Diamonsil ODS C18 column,
      with a mobile phase of MeOH-H2O (1:1, v/v) at a flow-rate of 1.0 mL/min, and UV
      detection was set at 330 nm. The calibration curve was linear over the range 0.2
      12.0 microg/mL (R2 = 0.9995) in rat plasma. The lower limit of detection and
      quantification were 0.01 and 0.1 microg/mL, respectively, using the rat plasma
      sample. The extraction recoveries were 77.36 +/- 4.56, 82.89 +/- 1.84 and 81.66
      +/- 2.49% at concentrations of 1.0, 5.0 and 10.0 microg/mL, respectively. The
      intra- and inter-day precision and accuracy were validated by relative standard
      deviation and relative error, which were in the ranges 5.07-5.83 and 3.95-6.29%,
      respectively. After i.v. administration to rats at a single dose of 40 mg/kg, the
      plasma concentration-time curve of nodakenin was best conformed to a two
      compartment open model. This assay method has been successfully applied to the
      study of the pharmacokinetics of nodakenin in rats.

PMID- 18318016
TI  - Determination of the lipophilic antipsychotic drug ziprasidone in rat plasma and
      brain tissue using liquid chromatography-tandem mass spectrometry.
AB  - A simple, sensitive and robust liquid chromatography/electrospray ionization
      tandem mass spectrometry (LCESI-MS/MS) method with low matrix effects was
      developed and validated for the quantification of the lipophilic antipsychotic
      ziprasidone from rat plasma and brain tissue. Ziprasidone was extracted from rat
      plasma and brain homogenate using a single-step liquid-liquid extraction.
      Ziprasidone was separated on an Agilent Eclipse XDB C8 column (150 x 2.1 mm i.d.,
      5 microm) column using a mobile phase of acetonitrile-0.02% ammonia in water (pH
      7.20 adjusted with formic acid) using gradient elution. Ziprasidone was detected
      in the positive ion mode using multiple reaction monitoring. The method was
      validated and the specificity, linearity, lower limit of quantitation (LLOQ),
      precision, accuracy, recovery, matrix effects and stability were determined. The
      LLOQ was 0.2 ng/mL for plasma and 0.833 ng/g for brain tissue. The method was
      linear over the concentration range from 0.2 to 200.0 ng/mL for plasma and 0.833
      833.3 ng/g for brain tissue. The correlation coefficient (R2) values were more
      than 0.996 for both plasma and brain homogenate. The precision and accuracy intra
      day and inter-day were better than 8.13%. The relative and absolute recovery was
      above 81.0% and matrix effects were lower than 5.2%. This validated method has
      been successfully used to quantify the rat plasma and brain tissue concentration
      of ziprasidone after chronic treatment.

PMID- 18318017
TI  - Identification of major alkaloids and steroidal saponins in rat serum by HPLC
      diode array detection-MS/MS following oral administration of Huangbai-Zhimu herb
      pair Extract.
AB  - Huangbai-Zhimu herb-pair (HBZMHP) is a widely used Chinese traditional medicine
      formula in treating various diseases; however, its active components have
      remained unknown. In this paper, serum chemistry and combined high-performance
      liquid chromatography (HPLC), diode-array detection and mass-spectrometry (MS)
      techniques were used to study the constituents of HBZMHP extract absorbed into
      rat serum after oral administration. A total of nine characteristic HPLC peaks in
      the TIC chromatograms were identified as magnoflorine (1), menisperine (2),
      palmatine (3), berberine (4), timosaponin N or timosaponin E1 (5), timosaponin D
      (6), timosaponin BIII, anemarsaponin C or xilingsaponin B (7) timosaponin BII (8)
      and timosaponin AIII (9). All of the identified peaks were constituents of HBZMHP
      extract. The results narrow the range of active compounds to be found in HBZMHP
      extract, and pave the way for the follow-up action mechanism research.

PMID- 18318018
TI  - Liquid chromatography/electrospray ionization tandem mass spectrometry for the
      quantification of mitiglinide in human plasma: validation and its application to
      pharmacokinetic studies.
AB  - A sensitive and specific method was developed and validated for the determination
      of mitiglinide in human plasma using liquid chromatographic separation with
      electrospray ionization tandem mass spectrometric detection. Acidified plasma
      samples were extracted with ethyl acetate. The chromatographic separation was
      performed on an Agilent Zorbax Eclipse Plus C(18) column with a mobile phase of
      methanol-10 mm ammonium acetate solution at a flow rate of 0.3 mL/min. Analytes
      were detected with an Agilent 6410 Triple qudrupole mass spectrometer equipped
      with an electrospray ionization source in positive multiple reaction monitoring
      mode: m/z 316.2 (precursor ion) to 298.2 (product ion) for mitiglinide and m/z
      318.2 (precursor ion) to 120.2 (product ion) for the internal standard. This
      method was validated over a linear range of 0.5-4000 ng/mL for mitiglinide in
      human plasma. The lower limit of quantification (LLOQ) was 0.5 ng/mL, while a
      relative standard deviation (RSD) was less than 3.9%. The intra- and inter-run
      precision (as RSD, %) obtained from three validation runs were all less than 15%.
      The validated method was successfully used to analyze human plasma samples for
      application in pharmacokinetic studies.

PMID- 18318019
TI  - Boldenone, testosterone and 1,4-androstadiene-3,17-dione determination in faeces
      from horses, untreated and after administration of androsta-1,4-diene-3,17-dione
      (boldione).
AB  - Faeces, which could be a potential alternative medium for doping control, have
      been used for the detection of 1,4-androstadiene-3,17-dione administration to the
      horse. Semi-quantitative analyses of 1,4-androstadiene-3,17-dione, testosterone,
      17alpha- and 17beta-boldenone have been conducted in pre- and post-administration
      faeces, and in controls (untreated stallions, geldings and mares). Sample
      preparation comprised diethyl ether extraction, lipid removal, HPLC purification
      and derivatisation. 1,4-Androstadiene-3,17-dione, testosterone, 17alpha- and
      17beta-boldenone were analysed by GC-EI/MS/MS. Quantitative limits of detection
      were 0.1 ng/g for 1,4-androstadiene-3,17-dione, and 0.025 ng/g for testosterone,
      17alpha- and 17beta-testosterone. In post-administration samples from geldings
      and mares, peak levels of 1,4-androstadiene-3,17-dione, 17alpha-, 17beta
      boldenone and testosterone were attained 24 h after administration. In untreated
      geldings and mares (in di- or anoestrus), 17alpha- and 17beta-boldenone and
      testosterone were not detected. Faeces from females in oestrus had detectable
      levels of boldenone isomers and testosterone. 1,4-Androstadiene-3,17-dione was
      undetectable in faeces collected from untreated horses, but the presence of this
      androgen was recently reported in faeces from untreated swine and it would
      therefore be advisable to check for its possible presence in a larger number of
      individual faecal samples.

PMID- 18318020
TI  - Divalent carbon(0) chemistry, part 1: Parent compounds.
AB  - Quantum-chemical calculations with DFT (BP86) and ab initio methods [MP2, SCS
      MP2, CCSD(T)] have been carried out for the molecules C(PH(3))(2) (1),
      C(PMe(3))(2) (2), C(PPh(3))(2) (3), C(PPh(3))(CO) (4), C(CO)(2) (5), C(NHC(H))(2)
      (6), C(NHC(Me))(2) (7) (Me(2)N)(2)C=C=C(NMe(2))(2) (8), and NHC (9), where NHC=N
      heterocyclic carbene and NHC(Me)=N-methyl-substituted NHC. The electronic
      structure in 1-9 was analyzed with charge- and energy-partitioning methods. The
      results show that the bonding situations in L(2)C compounds 1-8 can be
      interpreted in terms of donor-acceptor interactions between closed-shell ligands
      L and a carbon atom which has two lone-pair orbitals L-->C<--L. This holds
      particularly for the carbodiphosphoranes 1-3 where L=PR(3), which therefore are
      classified as divalent carbon(0) compounds. The NBO analysis suggests that the
      best Lewis structures for the carbodicarbenes 6 and 7 where L is a NHC ligand
      have C==C==C double bonds as in the tetraaminoallene 8. However, the Lewis
      structures of 6-8, in which two lone-pair orbitals at the central carbon atom are
      enforced, have only a slightly higher residual density. Visual inspection of the
      frontier orbitals of the latter species reveals their pronounced lone-pair
      character, which suggests that even the quasi-linear tetraaminoallene 8 is a
      "masked" divalent carbon(0) compound. This explains the very shallow bending
      potential of 8. The same conclusion is drawn for phosphoranylketene 4 and for
      carbon suboxide (5), which according to the bonding analysis have hidden double
      lone-pair character. The AIM analysis and the EDA calculations support the
      assignment of carbodiphosphoranes as divalent carbon(0) compounds, while NHC 9 is
      characterized as a divalent carbon(II) compound. The L-->C((1)D) donor-acceptor
      bonds are roughly twice as strong as the respective L-->BH(3) bond.

PMID- 18318021
TI  - Divalent carbon(0) chemistry, part 2: Protonation and complexes with main group
      and transition metal Lewis acids.
AB  - Quantum-chemical calculations with DFT (BP86) and ab initio methods (MP2, SCS
      MP2) were carried out for protonated and diprotonated compounds N-H(+) and N
      (H(+))(2) and for the complexes N-BH(3), N-(BH(3))(2), N-CO(2), N-(CO(2))(2), N
      W(CO)(5), N-Ni(CO)(3) and N-Ni(CO)(2) where N=C(PH(3))(2) (1), C(PMe(3))(2) (2),
      C(PPh(3))(2) (3), C(PPh(3))(CO) (4), C(CO)(2) (5), C(NHC(H))(2) (6),
      C(NHC(Me))(2) (7) (Me(2)N)(2)C==C==C(NMe(2))(2) (8) and NHC (9) (NHC(H)=N
      heterocyclic carbene, NHC(Me)=N-substituted N-heterocyclic carbene). Compounds 1
      4 and 6-9 are very strong electron donors, and this is manifested in calculated
      protonation energies that reach values of up to 300 kcal mol(-1) for 7 and in
      very high bond strengths of the donor-acceptor complexes. The electronic
      structure of the compounds was analyzed with charge- and energy-partitioning
      methods. The calculations show that the experimentally known compounds 2-5 and 8
      chemically behave like molecules L(2)C which have two L-->C donor-acceptor bonds
      and a carbon atom with two electron lone pairs. The behavior is not directly
      obvious when the linear structures of carbon suboxide and tetraaminoallenes are
      considered. They only come to the fore on reaction with strong electron-pair
      acceptors. The calculations predict that single and double protonation of 5 and 8
      take place at the central carbon atom, where the negative charge increases upon
      subsequent protonation. The hitherto experimentally unknown carbodicarbenes 6 and
      7 are predicted to be even stronger Lewis bases than the carbodiphosphoranes 1-3.

PMID- 18318022
TI  - Gold catalysis: deuterated substrates as the key for an experimental insight into
      the mechanism and selectivity of the phenol synthesis.
AB  - The second phase of the gold-catalyzed phenol synthesis, the ring opening of the
      intermediate arene oxide, follows general acid catalysis. The product selectivity
      is determined by the substrate only and can be explained by the stability of the
      intermediate arenium ions. Thus, even remote substitutents can be used to control
      the chemoselectivity of the overall reaction by electronic influences and their
      influence is stronger than the steric influence of neighboring substituents. This
      is supported by quantum chemical calculations of the intermediates. The lack of
      exchange of deuterium labels excludes even equilibria with acetylide or
      vinylidene intermediates and the observed deuterium distribution in the final
      products is in accord with the NIH-shift reaction. In addition, these findings
      now explain previously obtained results.

PMID- 18318023
TI  - Mechanism of charge separation in DNA by hole transfer through consecutive
      adenines.
AB  - To investigate the mechanism of charge separation in DNA with consecutive
      adenines adjacent to a photosensitizer (Sens), a series of naphthalimide (NI) and
      5-bromouracil ((br)U)-modified DNAs were prepared, and the quantum yields of
      formation of the charge-separated states (Phi) upon photo-excitation of the Sens
      NI in DNA were measured. The Phi was modulated by the incorporation site of
      (br)U, which changes the oxidation potential of its complementary A through
      hydrogen bonding and the hole-transfer rates between adenines. The results were
      interpreted as charge separation by means of the initial charge transfer between
      NI in the singlet excited state and the second- and third-nearest adenine to the
      NI. In addition, the oxidation of the A nearest to NI leads to the rapid charge
      recombination within a contact ion pair. This suggests that the charge-separation
      process can be refined to maximize the Phi by putting a redox-inactive spacer
      base pair between a photosensitizer and an A-T stretch.

PMID- 18318024
TI  - Mechanistic insights into the cobalt-mediated radical polymerization (CMRP) of
      vinyl acetate with cobalt(III) adducts as initiators.
AB  - Over the past few years, cobalt-mediated radical polymerization (CMRP) has proved
      efficient in controlling the radical polymerization of very reactive monomers,
      such as vinyl acetate (VAc). However, the reason for this success and the
      intimate mechanism remained basically speculative. Herein, two mechanisms are
      shown to coexist: the reversible termination of the growing poly(vinyl acetate)
      chains by the Co(acac)2 complex (acac: acetylacetonato), and a degenerative chain
      transfer process. The importance of one contribution over the other strongly
      depends on the polymerization conditions, including complexation of cobalt by
      ligands, such as water and pyridine. This significant progress in the CMRP
      mechanism relies on the isolation and characterization of the very first cobalt
      adducts formed in the polymerization medium and their use as CMRP initiators. The
      structure proposed for these adducts was supported by DFT calculations. Beyond
      the control of the VAc polymerization, which is the best ever achieved by CMRP,
      extension to other monomers and substantial progress in macromolecular
      engineering are now realistic forecasts.

PMID- 18318025
TI  - A new nanobiosensor for glucose with high sensitivity and selectivity in serum
      based on fluorescence resonance Energy transfer (FRET) between CdTe quantum dots
      and Au nanoparticles.
AB  - A novel assembled nanobiosensor QDs-ConA-beta-CDs-AuNPs was designed for the
      direct determination of glucose in serum with high sensitivity and selectivity.
      The sensing approach is based on fluorescence resonance energy transfer (FRET)
      between CdTe quantum dots (QDs) as an energy donor and gold nanoparticles (AuNPs)
      as an energy acceptor. The specific combination of concanavalin A (ConA)
      conjugated QDs and thiolated beta-cyclodextrins (beta-SH-CDs)-modified AuNPs
      assembles a hyperefficient FRET nanobiosensor. In the presence of glucose, the
      AuNPs-beta-CDs segment of the nanobiosensor is displaced by glucose which
      competes with beta-CDs on the binding sites of ConA, resulting in the
      fluorescence recovery of the quenched QDs. Experimental results show that the
      increase in fluorescence intensity is proportional to the concentration of
      glucose within the range of 0.10-50 muM under the optimized experimental
      conditions. In addition, the nanobiosensor has high sensitivity with a detection
      limit as low as 50 nM, and has excellent selectivity for glucose over other
      sugars and most biological species present in serum. The nanobiosensor was
      applied directly to determine glucose in normal adult human serum, and the
      recovery and precision of the method were satisfactory. The unique combination of
      high sensitivity and good selectivity of this biosensor indicates its potential
      for the clinical determination of glucose directly and simply in serum, and
      provides the possibility to detect low levels of glucose in single cells or
      bacterial cultures. Moreover, the designed nanobiosensor achieves direct
      detection in biological samples, suggesting the use of nanobiotechnology-based
      assembled sensors for direct analytical applications in vivo or in vitro.

PMID- 18318026
TI  - 1,2-Alkyl migration as a key element in the invention of cascade reactions
      catalyzed by pi-acids.
AB  - This brief overview highlights recent progress in the field of cascade reactions
      that are initiated by the activation of a pi-system using platinum and gold
      catalysts and that are coupled with a 1,2-alkyl migration step. While the
      reactions discussed aim to rapidly evolve molecular complexity, they are
      experimentally straightforward and easy to perform. Primarily guided by the type
      of 1,2-alkyl migration, methods are categorized as shifts to metal carbenoid
      centers and pinacol-type rearrangements.

PMID- 18318027
TI  - A shuttling molecular machine with reversible brake function.
AB  - Design, synthesis, and demonstration of a prototype of a shuttling molecular
      machine with a reversible brake function are reported. It is a photochemically
      and thermally reactive rotaxane composed of a dianthrylethane-based macrocycle as
      the ring component and a dumbbell shaped molecular unit with two, secondary
      ammonium stations separated by a phenylene spacer as the axle component. The rate
      of shuttling motion was shown to be reduced to less than 1 % (from 340 to <2.5 s(
      1)) by reducing the size of the ring component from 30-crown-8 to 24-crown-8
      macrocycles upon photoirradiation. The ring component was turned back to 30-crown
      8 by thermal ring opening, thus establishing a reversible brake function that
      works in response to photochemical and thermal stimuli.

PMID- 18318028
TI  - New rare earth metal complexes with nitrogen-rich ligands: 5,5'-bitetrazolate and
      1,3-bis(tetrazol-5-yl)triazenate-on the borderline between coordination and the
      formation of salt-like compounds.
AB  - From the two nitrogen-rich ligands BT(2-) (BT=5,5'-bitetrazole) and BTT(3-)
      (BTT=1,3-bis(1H-tetrazol-5-yl)triazene), a series of novel rare earth metal
      complexes were synthesised. For the BT ligand, a vast number of these complexes
      could be structurally characterised by single-crystal XRD, revealing structures
      ranging from discrete molecular aggregates to salt-like compounds. The
      isomorphous complexes [La2(BT)3]14 H2O (1) and [Ce2(BT)3]14 H2O (2) reveal
      discrete molecules in which one BT(2-) acts as a bridging ligand and two BT
      groups as chelating ligands. The complexes, [M(BT)(H2O)7]2[BT] x (x) H2O (3-5),
      (M=Nd (3), Sm (4), and Eu (5)), are also isomorphous and consist of
      [M(BT)(H2O)7]+ ions in which only one BT(2-) acts as a chelate ligand for each
      metal centre. [Tb(H2O)8]2[BT]3 x H2O (6) and [Er(H2O)8](2)[BT](3)x H2O (7) are
      salt-like compounds that do not exhibit any significant metal-nitrogen contacts.
      In the BTT-samarium compound 9, discrete molecules were found in which BTT(3-)
      acts as a tridentate ligand with three Sm--N bonds.

PMID- 18318029
TI  - Exogenous agents that target transmembrane domains of proteins.
AB  - Although membrane proteins account for approximately one third of all proteins
      encoded in the human genome, the functions and structures of their transmembrane
      domains are much less understood than the water-soluble regions. A major hurdle
      in studying these transmembrane domains is the lack of appropriate exogenous
      agents that can be used as specific probes. Despite the daunting challenges,
      major strides have recently been made in targeting the transmembrane domains of a
      variety of membrane proteins. High affinity and selectivity have been achieved in
      model biophysical systems, membranes of bacteria, and mammalian cells.

PMID- 18318030
TI  - Synthesis and structure of eight-, nine-, and ten-membered rings with P-Se-Se-P
      linkages.

PMID- 18318031
TI  - Highly efficient organic reactions "on water", "in water", and both.

PMID- 18318032
TI  - Total synthesis and structure assignment of papuamide B, a potent marine
      cyclodepsipeptide with anti-HIV properties.

PMID- 18318033
TI  - Iron-catalyzed S-arylation of thiols with aryl iodides.

PMID- 18318034
TI  - Room temperature copper-catalyzed 2-functionalization of pyrrole rings by a three
      component coupling reaction.

PMID- 18318035
TI  - Novel insight into inhibitor binding of highly symmetric HIV-1 protease.

PMID- 18318037
TI  - 100 years of bakelite, the material of a 1000 uses.

PMID- 18318036
TI  - Small molecule inhibitors targeting HIV-1 reverse transcriptase dimerization.
AB  - The enzymatic activities of human immunodeficiency virus type 1 (HIV-1) reverse
      transcriptase (RT) are strictly correlated with the dimeric forms of this vital
      retroviral enzyme. Accordingly, the development of inhibitors targeting the
      dimerization of RT represents a promising alternative antiviral strategy. Based
      on mutational studies, we applied a structure-based ligand design approach
      generating pharmacophoric models of the large subunit connection subdomain to
      possibly identify small molecules from the ASINEX database, which might interfere
      with the RT subunit interaction. Docking studies of the selected compounds
      identified several candidates, which were initially tested in an in vitro subunit
      association assay. One of these molecules (MAS0) strongly reduced the association
      of the two RT subunits p51 and p66. Most notably, the compound simultaneously
      inhibited both the polymerase as well as the RNase H activity of the retroviral
      enzyme, following preincubation with t(1/2) of about 2 h, indicative of a slow
      isomerization step. This step most probably represents a shift of the RT dimer
      equilibrium from an active to an inactive conformation. Taken together, to the
      best of our knowledge, this study represents the first successful rational screen
      for a small molecule HIV RT dimerization inhibitor, which may serve as attractive
      hit compound for the development of novel therapeutic agents.

PMID- 18318038
TI  - Analysis of case-control age-at-onset data using a modified case-cohort method.
AB  - Case-control designs are widely used in rare disease studies. In a typical case
      control study, data are collected from a sample of all available subjects who
      have experienced a disease (cases) and a sub-sample of subjects who have not
      experienced the disease (controls) in a study cohort. Cases are oversampled in
      case-control studies. Logistic regression is a common tool to estimate the
      relative risks of the disease with respect to a set of covariates. Very often in
      such a study, information of ages-at-onset of the disease for all cases and ages
      at survey of controls are known. Standard logistic regression analysis using age
      as a covariate is based on a dichotomous outcome and does not efficiently use
      such age-at-onset (time-to-event) information. We propose to analyze age-at-onset
      data using a modified case-cohort method by treating the control group as an
      approximation of a subcohort assuming rare events. We investigate the asymptotic
      bias of this approximation and show that the asymptotic bias of the proposed
      estimator is small when the disease rate is low. We evaluate the finite sample
      performance of the proposed method through a simulation study and illustrate the
      method using a breast cancer case-control data set.

PMID- 18318039
TI  - Generalized inferences on the overall treatment effect in meta-analysis with
      normally distributed outcomes.
AB  - This paper focuses on inferences about the overall treatment effect in meta
      analysis with normally distributed responses based on the concepts of generalized
      inference. A refined generalized pivotal quantity based on t distribution is
      presented and simulation study shows that it can provide confidence intervals
      with satisfactory coverage probabilities and perform hypothesis testing with
      satisfactory type-I error control at very small sample sizes.

PMID- 18318040
TI  - What's love got to do with it? Family cohesion and healthy eating behaviors in
      adolescent girls.
AB  - OBJECTIVE: To examine the association between family cohesion and behaviors
      linked to health or overweight in adolescents. METHOD: Cross-sectional analyses
      of family cohesion and eating behaviors of 2,379 girls (followed from ages 9-19)
      who participated in the National Heart, Lung, and Blood Institute Growth and
      Health Study (NGHS). Height and weight measurements were obtained on an annual
      basis. Family cohesion was measured by the Family Adaptability and Cohesion
      Evaluation Scale (FACES) III. Food diaries were used to assess frequency of
      breakfast consumption and intake of milk, soda, fruits, and vegetables. RESULTS:
      Family cohesion was significantly associated with less soda intake and higher
      rates of breakfast consumption. Ingestion of milk, fruits, and vegetables was
      predicted by family cohesion at the trend level. CONCLUSION: Understanding the
      role of familial factors in adolescent eating behaviors is an important research
      priority. Strengthening family cohesion may be a valuable goal toward promoting
      the health of adolescents, increasing breakfast eating and decreasing soda
      consumption.

PMID- 18318041
TI  - FGF2 secreting human fibroblast feeder cells: a novel culture system for human
      embryonic stem cells.
AB  - Human embryonic stem cell (hESC) lines are traditionally derived and maintained
      on mouse embryonic fibroblasts (MEF) which are xenogeneic and enter senescence
      rapidly. In view of the clinical implications of hESCs, the use of human
      fibroblast as feeders has been suggested as a plausible alternative. However, use
      of fibroblast cells from varying sources leads to culture variations along with
      the need to add FGF2 in cultures to sustain ES cell pluripotency. In this study
      we report the derivation of FGF2 expressing germ layer derived fibroblast cells
      (GLDF) from hESC lines. These feeders could support the pluripotency, karyotypes
      and proliferation of hESCs with or without FGF2 in prolonged cultures as
      efficiently as that on MEF. GLDF cells were derived from embryoid bodies and
      characterized for expression of fibroblast markers by RT-PCR, Immunofluorescence
      and by flow cytometry for CD marker expression. The expression and secretion of
      FGF2 was confirmed by RT-PCR, Western blot, and ELISA. The hESC lines cultured on
      MEF and GLDF were analyzed for various stemness markers. These feeder cells with
      fibroblast cells like properties maintained the properties of hESCs in prolonged
      culture over 30 passages. Proliferation and pluripotency of hESCs on GLDF was
      comparable to that on mouse feeders. Further we discovered that these GLDF cells
      could secrete FGF2 and maintained pluripotency of hESC cultures even in the
      absence of supplemental FGF2. To our knowledge, this is the first study reporting
      a novel hESC culture system which does not warrant FGF2 supplementation, thereby
      reducing the cost of hESC cultures.

PMID- 18318042
TI  - Recognition of rhesus macaque (Macaca mulatta) noisy screams: evidence from
      conspecifics and human listeners.
AB  - Vocalizations are among the diverse cues that animals use to recognize individual
      conspecifics. For some calls, such as noisy screams, there is debate over whether
      such recognition occurs. To test recognition of rhesus macaque noisy screams,
      recorded calls were played back to unrelated and related conspecific group
      members as either single calls or short bouts. Higher-ranking, but not lower
      ranking, monkeys looked longer toward the playback speaker in trials containing
      screams from kin than in those composed of screams from nonkin. In a second
      study, human listeners performed a "same/different" discrimination task between
      presentations of rhesus screams from either the same or two different monkeys.
      Listeners discriminated between "same" and "different" callers above an
      established empirical threshold, whether screams were presented singly or in
      short bouts. Together, these results suggest that rhesus monkeys can distinguish
      noisy screams between kin and nonkin, and humans are able to discriminate
      different individuals' noisy screams, even when the duration of the bout is
      short. Whether noisy screams are ideally designed signals for individual
      recognition is discussed with respect to possible evolutionary origins of the
      calls.

PMID- 18318043
TI  - Health-related quality of life in chronic hepatitis B patients.
AB  - The relationship between stages of chronic hepatitis B liver disease and health
      related quality of life (HRQoL) is an important aspect of the overall management
      of hepatitis B virus (HBV) infection, yet is not well characterized. Consequently
      we sought to examine HRQoL in HBV patients, stratified by disease severity,
      compared with normal controls and hypertensive patients, using the Short Form 36
      Health Survey (SF-36) and the EQ-5D self-report questionnaire. Univariate and
      multivariate analyses were then performed. A total of 432 HBV (156 asymptomatic
      carriers, 142 chronic hepatitis B, 66 compensated cirrhosis, 24 decompensated
      cirrhosis, 22 hepatocellular carcinoma, and 22 post-liver transplant) patients,
      93 hypertensive patients, and 108 normal controls participated in the study.
      Multivariate analysis showed that normal controls and asymptomatic carriers had
      similar SF-36 scores, which were better than those for hypertensive patients, but
      with development of chronic hepatitis B and compensated cirrhosis, showed a
      significant decrease in general health and the mental dimension, whereas those
      with advanced liver disease (decompensated cirrhosis and hepatocellular
      carcinoma) had significantly lower scores in all components (P < 0.05),
      indicating that the physical component deteriorates only with advanced liver
      disease. Similar results were obtained with EQ5D. Post-liver transplant patients
      had similar HRQoL to patients with decompensated cirrhosis and hepatocellular
      carcinoma, although there was a trend toward improvement. CONCLUSION: Our results
      showed that HRQoL in asymptomatic carriers is comparable to those of normal
      controls and better than hypertensive patients, but deteriorates with disease
      progression, initially in general health and mental dimensions, but with advanced
      disease all dimensions are affected.

PMID- 18318044
TI  - Describing and predicting psychological distress after colorectal cancer.
AB  - BACKGROUND: Psychological distress in cancer survivors can be detrimental to
      treatment adherence and self-care tasks and is associated with poor health
      behaviors and decreased overall quality of life. The prevalence, course, and
      predictors of psychological distress after the diagnosis of colorectal cancer are
      to date not well described. METHODS: A prospective survey of 1822 colorectal
      cancer patients was undertaken assessing psychological distress and hypothesized
      predictors including optimism, cancer threat appraisal, social support, and
      physical activity at 6 and 12 months postdiagnosis. Logistic regression
      identified correlates of psychological distress at 12 months postdiagnosis.
      RESULTS: The prevalence of global psychological distress was low: 8.3% and 6.7%
      at 6 and 12 months postdiagnosis, respectively. When baseline measures of
      independent variables were included in a logistic regression model, distress at 6
      months postdiagnosis (odds ratio [OR]=10.84), comorbidities (OR=1.64), optimism
      (OR=0.93), cancer threat appraisal (OR=0.92), and social support (OR=0.94) were
      significantly associated with distress at 12 months postdiagnosis. A second
      logistic regression model that included concurrent measures of cancer threat
      appraisal, social support, and physical activity found that distress at 6 months
      postdiagnosis (OR=12.49), comorbidities (OR=1.64), optimism (OR=0.94), and
      concurrent cancer threat appraisal (OR=0.85) were significantly associated with
      distress at 12 months postdiagnosis. CONCLUSIONS: Distress screening at regular
      intervals is needed to efficiently detect colorectal cancer patients who require
      in-depth psychological intervention. Threat appraisal is a modifiable variable
      that should be included in interventions for colorectal cancer survivors. Further
      research is needed to investigate the potential for physical activity to reduce
      distress after cancer.

PMID- 18318045
TI  - FAO and WHO urge all countries to be more vigilant about food safety. Recent food
      scares prove weaknesses in food safety systems around the world.

PMID- 18318046
TI  - New WHO pocket-charts will save lives by predicting heart attack and stroke.

PMID- 18318047
TI  - Parties to global tobacco control treaty take decisive steps to combat illicit
      tobacco trade and promote smoke-free environments.

PMID- 18318048
TI  - The report from the Sixty-third International Atlantic Economic Society
      conference held in Madrid, Spain, March 14-18, 2007.

PMID- 18318049
TI  - Discovery of new antitumoral and antibacterial drugs from brazilian plant
      extracts using high throughput screening.
AB  - Plants have played a significant role in the treatment of cancer and infectious
      diseases for the last four decades. The discovery and introduction to market of
      paclitaxel, the vinca alkaloids, etoposide, and many antibacterial drugs support
      drug discovery programs based on natural products. Natural products have been
      rediscovered as important tools for drug development despite advances in
      combinatorial chemistry, due to the complex molecular structures able to interact
      with mammalian cell targets. The Brazilian flora, the most diverse in the world,
      has become an interesting spot to prospect for new chemical leads or hits due to
      its species diversity and associated chemical richness. Screening programs have
      been established in Brazil as a strategy to identify potentially active
      substances. High throughput screening techniques allow for the analysis of large
      numbers of extracts in a relatively short period of time, and can be considered
      one of the most efficient ways of finding new leads from natural products. An
      updated review of the current status of the biological screening program is
      presented and recent results from new antitumoral and antibacterial chemical
      leads are discussed.

PMID- 18318050
TI  - Variations of dendritic cell-specific intercellualar adhesion molecule-3-grabing
      nonintegrin neck region in HIV infected individuals.

PMID- 18318051
TI  - [Simultant operative interventions in elective surgery of abdominal cavity].
AB  - The literature data concerning the problem of simultant operative interventions
      were analyzed and the unsolved topics were delineated. Basing on the detailed
      analysis of results of the operations obtained in 78 patients, performed for
      coexistent diseases, the authors consider the simultant operative interventions
      in elective surgery of the abdominal cavity the method of choice in presence of
      two-three coexistent diseases, which must be surgically treated.

PMID- 18318052
TI  - [The effect of low-molecular-weight heparin on the late follow-up results of the
      combined and complex treatment of patients with rectal cancer].
AB  - The late follow-up results of combined and complex treatment of 305 patients,
      suffering cancer recti, were analyzed. After the operation in 250 (82%) patients
      the anticoagulants were administered, including the low-molecular-weight heparin
      (calcium nadroparine)--129 (42.3%), and nonfractionized heparin--in 121 (39.7%).
      In 55 (18%) patients the complex and combined treatment was conducted, according
      to the present standards, without application of anticoagulants. There was
      proved, that administration of calcium nadroparine in combined and complex
      treatment of patients, suffering cancer recti, had promoted the patients three
      year and five-year survival indices increase due to reduction of the tumors
      generalization.

PMID- 18318053
TI  - [Colostasis in children].
AB  - The loss of the large bowel motor-evacuation function causes the metabolic
      processes disorder, the pain and not rare the patients invalidization due to
      chronic fecal intoxication incidence. That's why, the aim of surgical treatment
      of patients for chronic colostasis is their complete social rehabilitation. In
      1999-2004 yrs 107 patients were operated on, including those, suffering
      dolychosigm--54, Hirschsprung disease--15, megacolon--36, Pyre disease--2. The
      correct choice of the procedure as well as the rationality in the treatment
      tactics in chronic colostasis permits to determine the adequate volume of the
      operation choused.

PMID- 18318054
TI  - [Ischemic variant of cholecystocardial syndrome in the diseases of gallbladder].
AB  - There were analyzed 14 observations of patients suffering ischemic variant of
      cholecystocardial syndrome on the background of an acute calculous cholecystitis
      and cholecalculous disease. The rate of the pseudocoronary syndrome revealing was
      determined. The coding procedure using Minnesota's code was applied for the first
      time for ECG estimation in the patients.

PMID- 18318055
TI  - [Perspectives of using popliteo-tibial shunting in distal portions of the lower
      extremities arteries lesions].
AB  - In the treatment of ischemic disorders in patients, suffering diabetes mellitus,
      the venous shunting toward a. pedis dorsalis and/or paramalleolar segment of a.
      tibialis posterior are aplied most frequently. Distal shunting was performed in 3
      patients suffering critical ischemia of the lower extremities with possible
      alternative of amputation operation. The diameter and the state of internal
      vessel surface, the presence of its calcification, as well as the state of the
      blood inflow and outflow ways, had constituted the criterions of choice of
      certain segment of arteries for anastomosing. In the presence of several
      available vessels, the better surgical access to the artery and shorter way for
      shunting were taken into account. In 2 patients popliteoposterotibial shunting
      was performed, using autoven (1 observation) and the composed shunt (1
      observation); and in one--distal anastomosis was formed with a. pedis dorsalis.
      In 2 mo after the operation the composed shunt thrombosis occurred. In patients,
      to whom autovenous shunting was performed, the regional hemodynamics indices were
      stable, the shunts are functioning.

PMID- 18318056
TI  - [Chemotherapy of the small cell lung cancer using polyplatillen].
AB  - The experience of application of a new antitumoral platinum--containing
      preparation--polyplatyllen--in the treatment of the small cell pulmonary cancer
      was summarized. It was established, that the security profile of polyplatyllen is
      more favourable and efficacy in the treatment of the extended small cell
      pulmonary cancer is higher, than those of the standard scheme of treatment using
      cisplatinum and etoposide. The quality of life of the patients, while application
      of polyplatyllen, is more stable, than in application of the combined
      prescription of cisplatinum and etoposide.

PMID- 18318057
TI  - [Possibilities of plastic reconstructive surgery in the treatment of the skin
      defects on the head and neck].

PMID- 18318058
TI  - [Principles of prophylaxis of thrombosis and thromboembolism in oncosurgery].

PMID- 18318059
TI  - [The abdominal aorta aneurysm resection in a patient--Jehovah witness].

PMID- 18318060
TI  - [Observation of an acute arterial obstruction of the lower extremity, caused by
      the aortic wall dissection].

PMID- 18318061
TI  - [Esophageal resection for cicatricial stenosis on the background of the aquired
      immunodeficiency syndrome. Dangers and failures].

PMID- 18318062
TI  - [Incarcerated total vaginal hernia].

PMID- 18318063
TI  - [The changes of natural resistance of the patients with acute adhesive ileus].
AB  - The state of an organism natural resistance before and after the operative
      intervention for an acute adhesive ileus (AAI) was investigated. There was
      established, that the natural resistance of organism persisting after the
      operative intervention conduction constitutes the diagnostic criterion of the
      adhesive process progression in abdominal cavity and of the AAI recurrence
      occurrence.

PMID- 18318064
TI  - [The significance of intestinal decompression and lavage in the treatment of
      ileus and peritonitis].
AB  - The results of treatment of 67 patients, admitted to the hospital clinic for the
      spread peritonitis and ileus were studied. In 37 of them (main group) the
      intestinal decompression and hypothermic lavage was performed, in 30 (control
      group)--intestinal decompression only. The operation character and intensive
      therapy volume in patients of both groups were similar. In conduction of
      hypothermic intestinal lavage the accelerated restoration of intestinal
      peristalsis was noted, as well as the peritonitis and intoxication symptoms
      elimination. Duration of treatment of patients in stationary in the main and
      control groups had constituted, accordingly (11.6 +/- 0.73) and (16.8 +/- 1.03)
      days, lethality--8.1 and 13.8, frequency of complications--10.8 and 30%.

PMID- 18318065
TI  - [Application of lectin for studying of the erythrocytes membranes changes in an
      acute mechanical intestinal obstruction].
AB  - Osmoresistance and the erythrocytes membranes deformity were studied in 62
      patients, suffering an acute mechanical ileus, using lectin LPM. The lowering of
      indices, comparing with such in normal conditions, was established. While
      applying lectin, in tumoral ileus, in difference with nontumoral affection, the
      reduction of the erythrocytes membranes deformity was trustworthy (P < 0.01). In
      favourable course of postoperative period osmoresistance and deformity had
      approximated to normal values; in purulent complications occurrence the indices
      values had become poorer, these changes were strictly revealed using lectin. The
      method may be used for estimation of the treatment efficacy and the disease
      course prognosis.

PMID- 18318066
TI  - [Classification of chronic colostasis in children].
AB  - Chronic constipation--is a sign of many kinds of organic and functional affection
      of the colon and the rectoanal zone. It is observed in children of any age, it is
      characterized by durable absence of nonstimulated defecation act, as well as by
      various duration and severity. Constipation is delineated into a distinct
      disease, but classification of chronic colostasis, which meets the today's
      demands, is absent. The classification of chronic colostasis of their own is
      proposed by the authors, it reflects most entirely the causes and pathogenetic
      mechanisms of this failure in children.

PMID- 18318067
TI  - [Substantiation of perineal access to internal pudendal artery].
AB  - Perineal access to a. pudenda interna (API) was elaborated. Variants of the a.
      iliaca interna and her branches localization and topographic-anatomic
      peculiarities of perineal portion of API were studied. The proposed perineal
      (extraperitoneal) access to API is most expedient in the perineal region bleeding
      stopping. Morphometrical parameters of perineal portion of API permit to apply
      her for formation of vascular anastomosis in the procedure of revascularization
      of the descended colon while the intestinal continuity restoration.

PMID- 18318068
TI  - [Renal arteries stenting. Indications, procedure, results].
AB  - Vasorenal hypertension occurs approximately in 5% of patients, suffering arterial
      hypertension and in majority of them constitutes the consequence of the renal
      arteries stenosing atherosclerosis. Stenting constitutes the method of choice in
      the treatment of the renal artery stenosis. Endoprosthesis of renal artery was
      performed in 113 patients, in 10 of them--bilateral stenting. Angiographic effect
      was achieved in more than 98% of observations and the clinical one--in more than
      85%. Severe intraoperative complications were absent, all the patients are alive.
      In 13 patients the restenosis in the stent had occurred in 6-18 months after the
      operation, presenting by the clinical signs recurrence. To these patients the
      balloon angioplasty in the stent was accomplished. The depiction of technical
      peculiarities of the diagnosis and the procedure of the renal arteries stenting
      was suggested. According to modern recommendations of ACC/AHA, the stenting is
      indicated in the patients, suffering renal artery stenosis, and cardiac
      weaknesparoxysms, progressing arterial hypertension, unstable stenocardia,
      bilateral arterial affection. In the absence of symptoms, the efficacy of
      revascularization is not proved.

PMID- 18318069
TI  - [Prophylaxis of thromboembolism in general surgery: problems and perspectives].
AB  - In 52169 patients, suffering surgical diseases of abdominal cavity and operated
      in the clinic along 17 years, the prophylactic measures for venous thrombosis and
      pulmonary thromboembolism were analyzed. Pulmonary thromboembolism have had
      occurred postoperatively in 0.3% of patients and venous thrombosis--in 7/5%.
      Specific prophylaxis was done in 54.7%. In 1990-2006 yrs the occurrence rate of
      pulmonary thromboembolism reduced among other lethality causes from 12.2 to 5.7%.
      The main problem issues concerning the venous thrombosis and pulmonary
      thromboembolism prophylaxis in general surgery are enlightened, the perspectives
      of their solving are determined.

PMID- 18318070
TI  - [Prophylaxis of thromboembolic complications in bariatric surgery].
AB  - The efficacy of prophylaxis of tromboembolic complications in surgical treatment
      of 331 patients with morbid obesity, who underwent different bariatric
      operations, is estimated. The comparative analysis and results of application of
      non-fractionized heparin and low molecular weight heparins (Fraxiparin) in
      patients, suffering morbid obesity, are presented.

PMID- 18318071
TI  - [Use of simvatin for obliterating atherosclerosis after reconstructive operations
      on the main arteries of the lower extremities].
AB  - The results of application of simvatin in 207 patients after performance of
      reconstructive operations on the main arteries of femoro-popliteo-tibial segment
      were analyzed. Durable usage of simvatin had permitted to improve the immediate
      and the late results of reconstructive operations, to lower postoperative
      lethality significantly, caused by cardiovascular and vascular-cerebral
      insufficiency.

PMID- 18318072
TI  - [The survival indices of patients with stage IV gastric cancer treated by
      polyplatilen].
AB  - The survival indices of patients suffering gastric cancer stage IV in application
      of cytostatic preparation polyplatilen were studied up. The most expedient mode
      of treatment was suggested the conduction of no less than 2 courses of
      monochemotherapy. As a result, one year had survived (22.53 +/- 4.68)% patients,
      three years--(7.54 +/- 3.16)%, five years--(4.43 +/- 2.46)%.

PMID- 18318073
TI  - [First experience of bilateral hip joint prosthesis using DePuy ASR system].
AB  - Simultaneous bilateral hip joints prosthesis owes advantages over two-staged
      procedure, including the patients stationary treatment shortage, as well as
      duration of total operative time, total period of his disablement and financial
      expenses. Decision about application of such operations must be done
      individually, comparing the real criteria of risk for patient's life.

PMID- 18318074
TI  - [An acute obturation intestinal obstruction, caused by biliary concrement].

PMID- 18318075
TI  - [Incidental bacterial ascitis-peritonitis with pneumoperitoneum].

PMID- 18318076
TI  - [Rare observation of destructive diverticulum of colon ascendens].

PMID- 18318077
TI  - [The bleeding cessation using wax after removal of nonorgan retroperitoneal
      neurilemmoma].

PMID- 18318078
TI  - The massive medical coder shortage.

PMID- 18318079
TI  - Strategies for an effective call center.

PMID- 18318080
TI  - Access management back to basics.

PMID- 18318081
TI  - Managing the generation gap in healthcare.

PMID- 18318082
TI  - Is surgery still generally the first choice intervention in patients with carotid
      artery disease?
AB  - Five randomised trials (RCTs) provided the Level I, Grade A evidence which
      underpins (to this day) international guidelines regarding the roles of carotid
      endarterectomy (CEA) and best medical therapy in patients with symptomatic and
      asymptomatic carotid disease. However, since these trials were published, carotid
      angioplasty with stenting (CAS) has emerged as a viable alternative and triggered
      a completely new controversy. CAS offers potential advantages over CEA, but no
      fewer than eight RCTs have (so far) failed to translate 'potential' into clinical
      reality. More worryingly, some have questioned whether they ever will. The
      question posed for this debate is whether 'CEA should still remain the preferred
      first line intervention'. In order to answer this, it is essential to consider
      the evidence (separately) for patients deemed 'standard risk' (i.e. those
      randomised in ECST, NASCET, ACAS and ACST) as distinct from patients who are
      otherwise considered 'high risk'. The available evidence suggests that CEA
      remains the 'gold standard' in otherwise 'standard risk' patients outwith
      participation in RCTs. It is, however, likely that CAS could become the preferred
      intervention in selected 'high risk for surgery' symptomatic patients. However,
      evidence supporting a role for either CEA or CAS in 'high risk for surgery'
      asymptomatic patients remains poor. Many are probably best being treated
      conservatively.

PMID- 18318083
TI  - Carotid artery stenting: to be or not to be?
AB  - Carotid endarterectomy (CEA) has been the standard of care for suitable patients
      with symptomatic or asymptomatic high grade carotid stenosis since the landmark
      NASCET (North American Symptomatic Carotid Endarterectomy Trial), ECST (European
      Carotid Surgery Trial) and ACAS (Asymptomatic Carotid Artery Surgery) studies
      performed in the 1990s and more recently the ACST (Asymptomatic Carotid Surgery
      Trial). Carotid artery stenting (CAS) in the treatment of both symptomatic and
      asymptomatic patients with high grade carotid stenosis has recently been
      investigated as an alternative to CEA. We present a review of the most recent CAS
      trials and examine some of the controversies that surround them.

PMID- 18318084
TI  - The Rossetti-Nissen fundoplication--effective in managing gastro-oesophageal
      reflux disease.
AB  - BACKGROUND: The report herein details a prospective audit of a unit's eight-year
      experience of the Rossetti-Nissen fundoplication using a predominantly
      laparoscopic technique, selective hiatal repair, no bougie and a standardised
      protocol of pre- and post-operative functional endoscopic and symptom assessment.
      METHODS: Three hundred and seventy-eight patients underwent the Rossetti-Nissen
      fundoplication. All patients had documented data on endoscopy, health related
      quality of life (HR-QoL), surgical details and complications pre-operatively and
      at six months post-operatively. Repeat physiological testing was performed at six
      months. RESULTS: At a median follow-up of six (range 3-13) months there was
      improved symptom scoring and HR-QoL after fundoplication with an 89% patient
      satisfaction rate. Ninety-five patients (25%) reported some early dysphagia, and
      91 of these reported the outcome of surgery to be excellent or good. Thirty-eight
      patients (10%) had recurrent heartburn and 28 (7%) were back on medication at six
      months post-operatively. At follow-up pH study at a median of six months, 89% of
      patients had normalised acid reflux scores. CONCLUSIONS: Rossetti-Nissen
      fundoplication, with no use of an oesophageal bougie and no division of short
      gastric vessels, is an effective procedure giving 89% patient satisfaction and
      significant improvement in QoL parameters and physiological measurements.

PMID- 18318085
TI  - Current practice in management of Crohn's disease in Wales.
AB  - Crohn's disease (CD) demonstrates great heterogeneity in its presentation and
      severity. Management of CD is similarly diverse but the aim remains the same-
      remission of disease activity and improvement of health related quality of life
      (HR-QoL). Treatment options include steroids, 5-ASA derivatives, immunomodulators
      and surgery. The aim of this study was to define the variation in practice of
      consultant gastroenterologists and colorectal surgeons treating CD in Wales.
      METHODS: Consultant gastroenterologists and colorectal surgeons treating CD in
      Wales were sent a questionnaire aimed at determining their current practice and
      their responses were analysed. RESULTS: Eighty-eight consultants--46 (52%)
      gastroenterologists and 42 (48%) surgeons-- were invited to participate in the
      survey. Sixty-one (69%) of them responded. Coherent practice was seen across
      Wales, especially with respect to diagnosis of CD in line with British Society of
      Gastroenterology guidelines. Variation was detected in disease severity
      assessment and some aspects of management. CONCLUSION: Practice in Wales is in
      line with the guidelines for managing CD. While the diagnostic process follows a
      standard approach, variations exist in treatment and monitoring of disease.
      Validated disease measurement instruments are seldom used in routine practice.
      Disease assessment tools need to be simpler to use if they are to help objective
      measurement of disease activity and treatment decisions.

PMID- 18318086
TI  - Nerve injury in lower limb vascular surgery.
AB  - OBJECTIVE: Nerve injury is one of the most common complications of varicose vein
      surgery and is a frequent cause for litigation but its incidence following lower
      limb arterial surgery has not been well documented. This study was undertaken to
      determine the incidence of nerve injury following lower limb arterial surgery.
      This was addressed in relation to long saphenous or femoral vein harvesting, or
      re-operative surgery. MATERIALS AND METHODS: A total of one hundred patients who
      had undergone lower limb arterial reconstruction in the previous five years were
      invited to participate in this study. Seventy-eight patients responded, of which
      44 patients (66 operated legs) agreed to participate. They underwent neurological
      assessment of the lower limbs. RESULTS: 66.7% of limbs had objective evidence of
      sensory deficit following lower limb arterial surgery but none had motor deficit.
      Redo surgery or superficial femoral vein harvest had no influence on the
      incidence of nerve injury. Below knee incisions had a higher incidence of nerve
      injury than other approaches. Long saphenous vein harvest significantly increased
      the rate of nerve injury. CONCLUSIONS: There is a high incidence of sensory nerve
      damage following lower limb arterial surgery. In the present climate of
      increasing litigation it is important to know the likely incidence of post
      operative nerve damage so that patients can be counselled appropriately during
      the process of obtaining informed consent.

PMID- 18318087
TI  - Measuring competence in endoscopic sinus surgery.
AB  - BACKGROUND: Competence based education is currently being introduced into higher
      surgical training in the UK. Valid and reliable performance assessment tools are
      essential to ensure competencies are achieved. No such tools have yet been
      reported in the UK literature. OBJECTIVE: We sought to develop and pilot test an
      Endoscopic Sinus Surgery Competence Assessment Tool (ESSCAT). The ESSCAT was
      designed for in-theatre assessment of higher surgical trainees in the UK.
      METHODS: The ESSCAT rating matrix was developed through task analysis of ESS
      procedures. All otolaryngology consultants and specialist registrars in Scotland
      were given the opportunity to contribute to its refinement. Two cycles of in
      theatre testing were used to ensure utility and gather quantitative data on
      validity and reliability. Videos of trainees performing surgery were used in
      establishing inter-rater reliability. RESULTS: National consultation, the
      consensus derived minimum standard of performance, Cronbach's alpha = 0.89 and
      demonstration of trainee learning (p = 0.027) during the in vivo application of
      the ESSCAT suggest a high level of validity. Inter-rater reliability was moderate
      for competence decisions (Cohen's Kappa = 0.5) and good for total scores (Intra
      Class Correlation Co-efficient = 0.63). Intra-rater reliability was good for both
      competence decisions (Kappa = 0.67) and total scores (Kendall's Tau-b = 0.73).
      CONCLUSION: The ESSCAT generates a valid and reliable assessment of trainees' in
      theatre performance of endoscopic sinus surgery. In conjunction with ongoing
      evaluation of the instrument we recommend the use of the ESSCAT in higher
      specialist training in otolaryngology in the UK.

PMID- 18318088
TI  - Management of endoscopic retrograde cholangiopancreatography-related perforation.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation occurs
      in 0.1-1.8% of patients after therapeutic ERCP. It is a serious complication with
      a high mortality. However, little evidence exists in the medical literature and
      the optimal management remains unclear. This review aims to critically evaluate
      the optimal management of therapeutic ERCP-related perforation.

PMID- 18318089
TI  - Variation in surface marking of superior epigastric vessels. A guide to safe
      laparoscopic port insertion.
AB  - This study aimed to map surface markings of the superior epigastric artery, to
      provide safe landmarks for the placement of trochars in laparoscopic surgery.
      Seventeen cadavers were dissected and surface anatomy of the superior epigastric
      artery was defined at two levels: the xiphoid process, and midway between the
      xiphoid process and umbilicus. Safe sites for insertion of ports were determined
      in cadavers by dissecting and locating the main trunks of the superior epigastric
      artery. At the level of the xiphoid process, the distance from the midline ranged
      from 3.9cm to 4.8cm with a mean of 4.3cm (SD +/- 0.2cm) while midway between the
      xiphoid process and umbilicus, the distance of the superior epigastric artery
      from the midline ranged from 4 to 7.5cm, with a mean of 5.7cm (SD +/- 0.7cm). In
      this area the artery is vulnerable to damage, hence it can be declared as a
      danger zone.

PMID- 18318090
TI  - Substernal long segment left colon interposition for oesophageal replacement.
AB  - Long segments of colon, transposed on a vascular pedicle, have been used for
      oesophageal substitution for a long time. However the techniques employed for
      colonic reconstruction remain debated. We describe our substernal long segment
      replacement technique and emphasise several key aspects which are important in
      management of these patients. Optimising nutritional status and pulmonary
      function remain important aspects. Thymectomy allows room for the colonic segment
      preventing venous congestion. These patients are best managed in specialist units
      incorporating a multidisciplinary approach with good intensive care and
      radiological support.

PMID- 18318091
TI  - Hypoglycaemia in an adult male: a surprising finding in pursuit of insulinoma.
AB  - A 50-year-old man who had suffered several episodes of early morning sweats and
      tremors was diagnosed as having hyperinsulinaemic hypoglycaemia. Cross-sectional
      imaging and endoscopic ultrasound revealed no pancreatic lesion. A selective
      intra-arterial calcium infusion study showed a two-fold increase of insulin
      secretion after infusion of the splenic and superior mesenteric arteries.
      Laparotomy was performed, no lesion was identified after full mobilisation of the
      pancreas, and nothing was evident with intra-operative ultrasound. A distal
      pancreatectomy was performed. Microscopically, the pancreas exhibited diffuse
      islet cell hyperplasia consistent with nesidioblastosis. The patient remains
      euglycaemic eight months post-operatively.

PMID- 18318092
TI  - Re: Bioabsorbabale interference screws used in anterior cruciate ligament
      reconstruction: potential effects of postoperative infection.

PMID- 18318093
TI  - Evidence-based dental practice: part I. Formulating clinical questions and
      searching for answers.
AB  - Evidence-based dentistry (EBD) is an approach to oral health care that requires
      the judicious integration of systematic assessments of clinically relevant
      scientific evidence, relating to the patient's oral and medical condition and
      history, with the dentist's clinical expertise and the patient's treatment needs
      and preferences. Evidence-based care is now regarded as the "gold standard" in
      health care delivery worldwide. EBD involves tracking down the available
      evidence, assessing its validity and relevance, and then using the "best"
      evidence to inform decisions regarding care. Although, the concept of evidence
      based dentistry is not new, however, anecdotal evidence suggests that the
      awareness of this concept among Nigerian dental practitioners is low. This first
      of three articles on evidence-based dental practice discusses the historical
      background of evidence-based medicine/evidence-based dentistry, how to formulate
      clear clinical questions and how to track down (search) the available evidence in
      the literature databases.

PMID- 18318094
TI  - Adult lymphomas in Lagos Nigeria: a fourteen year study.
AB  - OBJECTIVE: we present a 14 year retrospective histopathological study of 92 cases
      of adult lymphomas in Lagos. The aim is to document the histologic types, age and
      sex distribution. MATERIALS AND METHOD: The materials consisted of slides and
      paraffin embedded blocks of all cases of lymphoma in adults above the age of 16
      years seen between 1991 and 2004 at the Morbid Anatomy Department of Lagos
      University Teaching Hospital Idi-Araba Lagos. RESULTS: Of ninety two cases of
      lymphoma studied, male and female patients accounted for 59(64%) and 33(36%)
      cases respectively, giving a M: F ratio of 1.8:1. The most frequently biopsied
      site is the cervical lymph node. Non-Hodgkin's lymphoma (NHL) which accounted for
      60 cases occurred most frequently in the 46-55 years age group and gives a male:
      female ratio of 2:1. Intermediate grade, high grade and low grade variants of
      NHLs accounted for 39%, 34% and 27% respectively. Hodgkin's lymphoma mostly
      affected patients of younger age group, 25-35 years with a M:F ratio of 1.7:1.
      Mixed cellularity 17 (55%) was the commonest subtype of Hodgkin's lymphoma.
      CONCLUSION: Non-Hodgkin's lymphoma is commoner than Hodgkin's lymphoma. The age
      and sex distribution agrees with reports from other parts of Nigeria and Africa
      with minimal variations.

PMID- 18318095
TI  - Migrated IUCD resulting in increased urinary frequency.
AB  - Missing Intrauterine contraceptive devices can migrate to various regions intra
      abdominally. Plain radiography usually confirms that the devise is still within
      the abdominal cavity, while other specific studies may define its relationship
      with the organ imaged. This is a case of a Migrated IUCD resulting in urinary
      symptoms.

PMID- 18318096
TI  - Comparison of the dimensional stability of alginate impressions disinfected with
      1% sodium hypochlorite using the spray or immersion method.
AB  - OBJECTIVE: To determine and compare the dimensional stability of alginate
      impressions disinfected with Sodium hypochlorite using the spray and immersion
      methods. METHODOLOGY: Alginate impressions of a master model of truncated metal
      cones were made and disinfected with 1% sodium hypochlorite constituted from 3.5%
      household bleach using the spray and immersion technique for 10; 20 and 30
      minutes. Impressions were cast in dental stone and the linear dimensional
      differences between the inter-abutment distances were measured with an electronic
      caliper. One sample T test and percentage differences were calculated. RESULT:
      There were no statistically significant differences in dimensions of alginate
      impressions of the control and those disinfected by either spraying or immersion
      methods when compared with the master model at 10 minutes. However, there was a
      statistically significant difference at 20 and 30 minutes. The spray technique
      showed the least percentage difference from the master model. CONCLUSION:
      Disinfection of alginate impressions with 1% sodium hypochlorite constituted from
      commercially available household bleach by the spray or immersion techniques for
      ten minutes will produce casts with minimal dimensional changes.

PMID- 18318097
TI  - Medication errors in paediatric outpatient prescriptions of a teaching hospital
      in Nigeria.
AB  - BACKGROUND: Proper and adequate pharmacovigilance is lacking in children's drug
      therapy, especially in developing countries. Therefore these children are at risk
      of developing adverse reactions to drugs as a result of medication errors. Having
      a better understanding of the types of error in a teaching hospital would be an
      important step toward quality improvement in children drug therapy. OBJECTIVES:
      This study was aimed at identifying the medication errors most frequently
      committed in the paediatric outpatient prescriptions at the Lagos State
      University Teaching Hospital, Ikeja and to suggest effective strategies for
      reducing these errors. METHODS: A total of 2,000 paediatric outpatient
      prescriptions randomly selected from five months prescriptions were studied.
      Information extracted from the prescription forms are age, sex and the drug
      prescription proper (adequacy of the dosage and duration of use; generic or trade
      name prescription; using abbreviation or acronym; prescribing injections in
      millilitres or milligram, syrup or suspensions in millilitres or milligram,
      tablets in unit numbers or milligram; and giving instructions on how to use the
      drugs in the case of drug-drug, drug-disease or drug-food interactions). RESULTS:
      A total of 1944 prescriptions met the criteria for inclusion in the study.
      Antimalarials (89.9%), analgesics (66.4%), vitamin B complex (61.5%) and
      antibiotics (41.4%) were the most prescribed drugs. Errors identified are
      inadequate medication dosing duration; omission of age, dosage, and duration of
      drug use; improper dosaging and prescription of those drugs that could adversely
      interact. While paracetamol, 94.6% of the analgesics, was prescribed for an
      average of 3.2 +/- 0.6 days, antibiotics were prescribed for an average of 6.2 +/
      1.0 days. Duration of use was omitted in 24 (2.0%) and 12 (1.5%) prescriptions
      for paracetamol and antibiotics respectively. Errors of overdosaging and
      underdosaging were common to most of the commonly prescribed drugs. Underdosage
      and overdosage were associated with 2518 (38.0%) and 1247 (18.8%) drugs
      respectively. There was a significant difference in the dosage error made in the
      prescription of tablets in mg/kg and in unit number of tablets (/2 = 148.42) and
      in the prescription of syrups/suspensions in millilitre and in mg/kg (/2 =
      95.58). Inadequate and omission of the duration of use of the drugs were observed
      in 1981(28.3%) and 61(0.9%) prescriptions respectively. CONCLUSION: Children
      presenting to the LASUTH are at a greater risk of adverse drug reactions from
      overdosage prescriptions and are also facing the risk of treatment inadequacy and
      failure from underdosage prescriptions. Therefore a monitoring committee is
      urgently required to be put in place to review all paediatric prescriptions for
      appropriateness, adequacy and dosage accuracy using the patient's weight, age,
      and other appropriate indicator(s) before dispensing and/or refill for paediatric
      patients. Also rational drug prescription should form part of the monthly
      continuous medical education of the hospital with much focus on the paediatric
      doctors.

PMID- 18318098
TI  - Evidence-based paradigm in orthodontics.
AB  - The need to integrate the accrued scientific evidence into clinical orthodontic
      practice is amongst the challenges facing orthodontists in the 21st century. The
      evidence-based health care approach aims to improve patient care based upon
      informed decision-making. This article therefore highlights the importance and
      application of evidence-based approach in orthodontic management of patients.

PMID- 18318099
TI  - Effect of sodium salicylate iontophoresis in the management of hip pain in
      patients with sickle cell disease.
AB  - BACKGROUND: Iotophoresis is a means of delivering drugs across the skin for the
      management of a variety of conditions, most often for localized inflammation and
      pain. It is becoming popular as an alternative to oral and injection delivery
      system because it is non-invasive, non-traumatic, and painless and also because
      of its specific delivery system. OBJECTIVE: The objective of this study was to
      determine the effectiveness of sodium salicylate iontophoresis in the management
      of hip pain in patient with sickle cell disorders (SCD). METHOD: The participants
      for this study were 20 patients with SCD, their ages ranged from 15-30 years.
      They were randomly assigned into two groups of 10 (study and control groups. All
      the participants were given conventional physiotherapy and their regular
      medications. In addition sodium salicylate iontophoresis was giving to the
      affected hip of the participants in the study group using a galvanic current
      machine. Pain intensity and range of motion at the hip joint were assessed at the
      beginning and after 10 treatment sessions. Data were analyzed using Mann Whitney
      U test and paired t-test for the visual analogue scale and goniometric values
      respectively. RESULT: The results showed that there was a statistically
      significant reduction in pain intensity only in the participants in the study
      group (p<0.05), there was also a statistically significant improvement in the hip
      range of motion of the participants in the study group (p<0.05). CONCLUSION: It
      was concluded that sodium salicylate iontophoresis was effective in the
      management of hip pain in patients with SCD. It is therefore recommended for
      routine use for patients with SCD on admission with severe pain.

PMID- 18318100
TI  - The intricacies of histopathological procedures and techniques.
AB  - BACKGROUND: Histopathology is basically the microscopic differentiation of normal
      from abnormal cells and tissues hence normal cells must not be made to look
      abnormal or vice versa during preparations. Some laboratories do not follow the
      adequate procedures that can pass Quality Assurance Test thereby giving false
      impression on slides and subsequently false reports. OBJECTIVE: This paper
      attempts to demonstrate the intricacies of histological procedures and techniques
      highlighting reasons why it is inevitable to follow the various precautionary
      measures in the production of valuable sections that will give the required
      results. METHOD: The bulk of this report is made up of personal laboratory
      experiences (its successes and failures), also wide and extensive research from
      secondary data (text books and manuals). RESULT: Carelessly made sections will
      give false reports that will mislead the pathologist. It will not present the
      tissue as it was in vivo as required. CONCLUSION: Precisely made sections that
      show trivial details are the only ones that can give authentic and reliable
      reports expected for patient's diagnosis, research work or teaching purposes.

PMID- 18318101
TI  - Pattern of ocular emergencies seen at L.U.T.H. over a period of 1 year.
AB  - AIM: To determine the commonest type of ocular emergencies seen at L.U.T.H. over
      a period of one year. METHODOLOGY: Data of all consecutive patients seen as
      emergencies within the designated period was taken. These included age, sex,
      symptoms, signs, agents of injury, duration and the complications. RESULTS: A
      total of 304 patients were seen. 207 (68.0%) of them were males, while 97 (32.0%)
      of them were females giving a ratio of 2.1:1. Out of the total number, 159
      (52.3%) had non-injurious emergencies. Of the 145 (47.7%) injurious emergencies,
      blunt trauma was the commonest with 77 patients (25.3%). Penetrating trauma was
      next in frequency with 37 patients (12.2%) as compared to blunt injury with 77
      patients. Foreign body injuries were seen in 18 patients (5.9%), followed by
      chemical injuries which constituted the least with 13 patients (4.3%).
      CONCLUSION: Majority of the ocular emergencies seen were due to non-injurious
      type, while blunt trauma was the commonest of the injurious type. RECOMMENDATION:
      Health education and awareness creation should be intensified on the various
      causes of the ocular emergencies, more importantly on the non-injurious causes to
      prevent the resultant ocular morbidity.

PMID- 18318102
TI  - Obesity: a review of its implications and considerations in oral and
      maxillofacial surgery.
AB  - Obesity is defined as the accumulation of fatty tissue to such a level that
      overall health might be adversely affected. It is a complex, multifactorial
      metabolic condition which develops from interactions of genetic and environmental
      factors. The prevalence of obesity is increasing at an alarming rate in many
      parts of the world including developing countries. Subsequently, increasing
      number of obese patients is expected to present for oral and maxillofacial
      treatment. Such treatment includes routine oral and maxillofacial procedures
      (teeth extraction, fracture fixation, biopsies), specific corrective procedures
      for snoring and obstructive sleep apnea, and intermaxillary fixation for weight
      reduction. Obese patients provide a unique challenge because of their body
      habitus, medical conditions, and physiologic, response to treatment, all of which
      have significant consequences on the surgical procedure being performed.
      Therefore, the oral and maxillofacial surgeon needs to be aware of these
      associated medical and surgical issues and take them into consideration when
      treating these patients. This article reviews the clinical and surgical
      implications that obesity has on the delivery of oral and maxillofacial surgical
      and anaesthetic care.

PMID- 18318103
TI  - Prevalence of iron deficiency in children 6-24 months in Lagos.
AB  - BACKGROUND: Iron deficiency is the commonest cause of nutritional anaemia in
      children worldwide particularly in developing countries. Infants and toddlers are
      prone to developing iron deficiency anaemia (IDA). This study was carried out to
      determine the prevalence of IDA and some factors associated with it in this group
      of children. STUDY DESIGN: Haemoglobin concentration and mean corpuscular volume
      (MCV) estimations carried out in 282 apparently well children aged 6-24 months.
      Estimations of serum iron (SI), total iron binding capacity (TIBC), serum
      ferritin (SF) and transferrin saturation (TS) were also determined in children
      with anaemia (Hb concentration < 11.0 g/dl). Information on current diet was also
      obtained using a diet record. RESULTS: Two hundred and twenty three (79.1%)
      children had anaemia. The mean Hb concentrations of all the age groups were less
      than 11.0 g/dl. Forty (14.9%) children had IDA (defined as aneamia plus 2 or more
      of the following--MCV < 70fl, Ts < 10% or SF < 10 microg/dL). The mean age of
      children with IDA (8.96 +/- 2.54 months) was statistically lower than for those
      without the condition 10.94 +/- 4.55 months (p = 0.016). Inclusion of vegetables
      and animal protein less than three times a week in the diet were both
      significantly associated with IDA. CONCLUSION: The prevalence of IDA in this
      study is high especially before the age of 12 months and an average weekly intake
      less than 3 times a week or iron rich foods like animal protein and vegetables
      was significantly associated with IDA. Emphasis should be on the inclusion of
      iron rich foods in the diet following exclusive breastfeeding to reduce the
      prevalence of IDA in these children.

PMID- 18318104
TI  - Medical students' view on the methods of teaching pharmacology at the Lagos State
      University College of Medicine, Nigeria.
AB  - OBJECTIVE: This study was aimed at determining the perception of the medical
      students of a relatively new medical school in Nigeria about the teaching of
      Pharmacology, the best way of learning and retaining the subject. Suggestions on
      the ways of making pharmacology more interesting to them were also sought.
      METHODS: A total of forty eight 400 level medical students of the Lagos State
      University College of Medicine (LASUCOM), who were due to write 2nd Professional
      M.B; B.S degree examinations in 2007 and 26 successful older students that had
      passed the 2nd Professional M.B; B.S degree examinations in 2006, were
      interviewed with a structured questionnaire. Some of the questions were close
      ended but the ones related to suggestion on impaired teaching of the subject were
      open-ended. The pharmacology lecturers were also interviewed with another
      questionnaire, different from the one used in interviewing the students, to
      assess their views on the non-inclusion of clinical pharmacology topics to the
      curriculum and to suggest ways of improving the teaching of the subject. RESULTS:
      Sixteen (41.02%) respondents and 26 (92.86%) successful older students wanted
      audiovisual aids teaching and inclusion of clinically oriented pharmacology
      lectures. Fourteen (35.89%) respondents respectively and all the successful older
      students wanted seminars and group discussions introduced into their programme.
      Over half (58.97%) of the respondents and all the successful older students
      wanted case studies and treatment as part of the regular teaching schedule, 20
      (51.28%) respondents and 20 (76.92%) successful older students preferred
      inclusion of clinical pharmacology. Most of the students (respondents and older
      successful students) felt that special topics in clinical pharmacology should be
      taught both in the lectures and practical. CONCLUSION: Medical students are very
      willing to learn pharmacology from both clinical and therapeutic angles that
      encompass both theoretical and practical approaches. It is therefore imperative
      to modify the Pharmacology programme of the LASUCOM in line with the global
      trend.

PMID- 18318105
TI  - Changes in plasma concentration of serotonin in response to spinal stabilisation
      exercises in chronic low back pain patient.
AB  - BACKGROUND: Currently, there is evidence demonstrating the efficacy of
      stabilisation exercises in the management of acute and chronic low back
      disorders. However, the main facilitation techniques behind the efficacy of this
      exercise still remain uncertain. OBJECTIVE: The purpose of the study was to
      investigate the changes in the plasma levels of serotonin in response to spinal
      stabilisation exercises in participants with chronic low back pain. METHODS:
      Twenty-two participants (11 males, 11 females) with chronic low back pain
      volunteered to the take part in this study. The main outcome measures used in
      this study were plasma levels of serotonin measured with Enzyme linked immuno
      absorbent assay (ELISA) technique. Participants were randomly allocated either to
      the stabilisation exercise groups, where they carried out stabilisation exercise
      training or the control (no exercise) group. RESULTS: The results showed
      significant increase in plasma serotonin level by 17.8% in the exercise groups
      immediately following active exercise, which was not noticed in the control
      group. CONCLUSION: It could also be that an increase in plasma serotonin levels
      produced with the use of stabilisation exercise may have a role to play in the
      positive out come of stabilisation exercise in the management of chronic low back
      pain.

PMID- 18318106
TI  - Oral hygiene practices among adolescents in Surulere, Lagos State, Nigeria.
AB  - OBJECTIVE: To determine the oral hygiene practices of adolescents attending
      schools within Surulere, a Local Government Area in Lagos, Nigeria. METHOD: A
      questionnaire enquiring about oral hygiene practices such as method of oral
      cleansing and frequency, and attitude to professional prophylaxis was
      administered to 600 adolescents. Demographic data such as sex, age, social class
      and ethnic group was also obtained. RESULTS: The majority (96.3%) of the subjects
      used toothbrush and paste only for oral hygiene. The use of the chewing stick
      combined with toothbrush/paste was practiced by nearly 4% of the subjects seen. A
      significant difference in the method of oral hygiene was observed among the
      social classes, with the use of chewing stick in combination with
      toothbrush/paste being more prevalent among the lower social classes than the
      higher social classes. Oral hygiene was carried out at least once a day by 97% of
      the subjects. Nearly all subjects (95.5%) had never been to the dental clinic for
      professional prophylaxis (scale and polish), with less than 1% routinely visiting
      the dental clinic for professional prophylaxis once or twice yearly. CONCLUSION:
      The use of toothbrush and paste appears to have increased slightly when compared
      to previous studies among this group. There is need for oral health education on
      the frequency of use of the toothbrush and the importance of routine dental
      visits and professional prophylaxis among the population especially the lower
      social classes.

PMID- 18318107
TI  - Telfairia occidentalis extract stabilizes human erythrocyte membranes.
AB  - In addition to being a widely consumed vegetable in West Africa, the leaves
      extract of Telfairia occidentalis is believed to have beneficial health effects
      and is used in tradomedical preparations. The effect of saline extract of T.
      occidentalis leaves on sickle and normal erythrocytes membrane stability was
      investigated. Human erythrocytes exposed to hypotonic and heat stress, by
      incubation in a buffered hypotonic medium at 56 degrees C, were stabilized by the
      extract in a doze dependent manner. The maximum stability was 72.3 +/- 3.1% and
      55.0 +/- 4.1% for the sickle and normal erythrocytes membrane respectively (p <
      0.0001). This study indicates that T. occidentalis has human erythrocyte membrane
      stabilizing activity. In addition the marked difference in the observed effect
      between the normal and sickle erythrocytes membranes suggests that
      pharmacogenetic factors may be involved in the response to herbal preparations.

PMID- 18318108
TI  - Evidence-based dental practice: Part II. Levels and quality of evidence, and
      research designs.
AB  - The ability to make a sound clinical decision is based largely on the quality of
      evidence and the practitioner's ability to evaluate this evidence. Clinical
      evidence are categorized and ranked according to the strength of their freedom
      from the various biases that beset medical research. Randomized controlled trials
      (RCTs) are the "gold standard" by which all clinical research is judged.
      Systematic reviews/meta-analysis of randomized controlled trials where available
      are considered the highest level in the evidence hierarchy (clinical questions
      related to therapy or interventions). However, this hierarchy of evidence can not
      answer all clinical questions especially the ones regarding diagnosis, aetiology
      or prognosis. For questions related to diagnosis, prognosis or causation, other
      study designs such as longitudinal studies, cohort studies or case-control
      studies are more appropriate. The present article discusses the levels and
      quality of evidence, and basic concepts of clinical research design in evidence
      based dental practice based on review of existing literature.

PMID- 18318109
TI  - Roles of the hypocretin/orexins in the regulation of sleep and wakefulness.
AB  - Hypocretin/orexin is produced exclusively in the dorsal and lateral hypothalamus
      but its projection is widespread within the brain and plays important roles. In
      this paper, we review the independent discoveries of the hypocretin/orexin
      peptides, the neuroanatomy of this system, and the link to the sleep disorder
      narcolepsy that has led to the idea that this system plays a crucial role in the
      regulation of sleep and wakefulness.

PMID- 18318110
TI  - Establishment of a laboratory colony of taiga tick Ixodes persulcatus for tick
      borne pathogen transmission studies.
AB  - Ixodes persulcatus Schulze (I. persulcatus) is distributed in Russia and Far East
      Asia including Japan, and has been implicated as the vector of several human
      pathogens. In particular, I. persulcatus acts as the only tick vector for human
      lyme borreliosis in Japan. In order to elucidate the mechanism of transmission of
      I. persulcatus-borne pathogens, we developed a laboratory colony of I.
      persulcatus. Ticks were fed on Syrian hamster and engorged ticks that had dropped
      off the animals were collected and maintained to allow them to molt. Tick rearing
      was performed in incubator at 20 degrees C with 95% relative humidity and 12-hour
      light/dark photo-period regimen. We found out that adult females fed for 8 +/- 2
      days and had a pre-oviposition period lasting for 7 +/- 2 days. The minimum egg
      incubation period was 1 month with the hatched larvae feeding for 3 +/- 1 days
      and molting to nymphs 3-4 months thereafter. Meanwhile, the nymphs fed for 4 +/-
      1 days and molted to adult 2-3 months thereafter. For future analysis of gene
      expression profiles in I. persulcatus, we cloned and sequenced the actin gene (a
      housekeeping gene), and found that it is 92.7% to 98.6% homologous to the
      published sequences of related ixodid ticks. This laboratory colony of I.
      persulcatus will facilitate investigations on the role of tick-derived molecules
      on the transmission of I. persulcatus-borne pathogens and will be important for
      identification of potential anti-tick vaccine and acaricide target molecules.

PMID- 18318111
TI  - Development of vaccine strains of H5 and H7 influenza viruses.
AB  - To establish vaccine strains of H5 and H7 influenza viruses, A/duck/Hokkaido/Vac
      1/04 (H5N1) [Vac-1/04 (H5N1)], A/duck/Hokkaido/Vac-3/07 (H5N1) [Vac-3/07 (H5N1)],
      and A/duck/Hokkaido/ Vac-2/04 (H7N7) [Vac-2/04 (H7N7)] were generated from non
      pathogenic avian influenza viruses isolated from migratory ducks. Vac-1/04 (H5N1)
      and Vac-3/07 (H5N1) were generated by genetic reassortment between H5N2 or H5N3
      virus as an HA gene provider and H7N1 or H6N1 viruses as an NA gene provider. Vac
      2/04 (H7N7) was a genetic reassortant obtained using H7N7 and H9 N2 viruses to
      give high growth character of the H9N2 virus in chicken embryonated eggs. The
      results of sequence analyses and experimental infections revealed that these H5N1
      and H7N7 reassortant viruses were non-pathogenic in chickens and embryos, and had
      good growth potential in embryonated eggs. These viruses should be useful to
      develop vaccines against H5 and H7 highly pathogenic avian influenza viruses.

PMID- 18318113
TI  - [Non-standard genetic codes and translation termination].
AB  - Genetic code is not universal. Various non-standard versions of the code were
      found in mitochondrial, prokaryotic and eukaryotic genomes. Stop codons are used
      to signal the ribosome stop translation of the coding sequence and prone to
      reassignment to sense codons. Class-1 termination factors recognize stop codons
      and promote hydrolysis of the peptidyl-tRNA in ribosome (RF1, RF2 in prokaryotes
      and eRF1 in eukaryotes). The class-1 factor termination specificity is changed in
      non-standart codes organisms. Pyrrolysine and selenocysteine use dissimilar
      decoding strategies. The various non-standart code origin hypotheses are
      described. It was proposed that specificity alteration of the class-1 release
      factor was a starting point for stop codon reassignment.

PMID- 18318112
TI  - [The use of p53 as a tool for human cancer therapy].
AB  - The p53 tumor suppressor is a central component of a system that reinforces
      genetic stability of somatic cells in animals and humans. Inactivation of this
      gene occurs virtually in every cancer case, which eliminates results in further
      rapid accumulation of additional mutations leading to progression of a cancer
      cell toward more malignant phenotype. The mechanisms of p53 inhibition in cancer
      include point mutations leading to accumulation of inactive protein, deletion of
      the whole gene, or its portion, alteration in the genes involved in regulation of
      activity of p53, and defects in the genes controlled by p53. In addition,
      oncogenic viruses encode specialized proteins that are entitled to modify p53
      functions in order to provide optimal condition for replication of viral genome.
      These viral proteins play central role in viral carcinogenesis, including 95% of
      cases of cervical carcinoma in women. The approacheas to restoration of p53
      activity depend on particular type of alteration within the p53 pathway. In some
      cases an effective mean would be introduction of exogenous p53, particularly with
      the use of adenoviral vectors. There are also approaches in development that
      target reactivation of mutant proteins, or suppress natural inhibitors of p53.
      The review summarizes various schemes for therapy and prevention of cancer that
      are based on our knowledge of the p53 gene functions. Potential usefulness of the
      approaches for practical applications is discussed.

PMID- 18318114
TI  - [Homology-dependent inactivation of LTR retrotransposons in genomes of
      Aspergillus fumigatus and A. nidulans].
AB  - Repeat-induced point mutation (RIP) is the most intriguing among the known
      mechanisms of repeated sequences inactivation because of its ability to produce
      irreversible mutation of repeated DNA. Discovered for the first time in
      Neurospora crassa, RIP is characterized by C:G to T:A transitions in duplicated
      sequences. The mechanisms and distribution of RIP are still purely investigated.
      Mobile elements are a common target for the processes which lead to homology
      dependent silencing because of their ability to propagate themselves. We have
      done comparative analysis of LTR retrotransposons in genomic scale from genomes
      of two aspergilli fungi--Aspergillus funmigatus and A. nidulans, based on several
      copies we reconstructed "de-RIP" retroelements. Investigations of frequencies of
      CpG, CpA and TpG sites, which are potential targets for mutagenesis, showed the
      much lower frequencies of these sites in mobile elements in comparison with
      structural genes. LTR retrotransposons from A. fumigatus and A. nidulans have
      different ratio of types of substitutions. Our analysis indicates that two
      investigated fungi have or had the RIP-like processes for repeated sequences
      inactivation, in various modes. Whereas in A. fumigatus the context for
      mutagenesis consists of both CpG and CpA sites, in A. nidulans inactivation seems
      to proceed only on CpG dinucleotides. The present investigation gives a
      theoretical background for planning of experimental studying of RIP inactivation
      in aspergilli.

PMID- 18318115
TI  - [Polymorphism of human MDR1 gene in the Siberian and central Asian populations].
AB  - The multidrug resistance gene (MDR1, ABCB1) encodes transmembrane P-glycoprotein
      an ATP-dependent transporter, which is involved in elimination of drugs,
      xenobiotics, peptides from a cell. It is expressed in such organs as a brain,
      kidneys, a liver, a gastroenteric tract. It is supposed, that this protein may
      take part in formation of individual resistance to action of adverse factors of
      an environment, such as toxic substances, xenobiotics and infectious diseases. A
      number of polymorphisms in MDR1 gene is associated with a expression level and
      functioning of the gene, as well as with the ability to eliminate drugs and with
      the resistance to various neurodegeneration and gastroenteric tract diseases. In
      this study the frequencies of five single nucleotide polymorphisms (SNPs)
      (3435C/T, 2677G/T/A, 1236C/T, +139C/T and -1G/A), located in MDR1 gene,
      frequencies of haplotypes, the genetic differentiation and linkage disequilibrium
      pattern in populations of Russians, Tuvinians, northern and southern Kirghizes
      are described. Significant genetic differences were found between populations of
      Russians and northern Kirghizes, and also between Tuvinians and northern
      Kirghizes. The linkage disequilibrium pattern is characterized by high population
      specificity.

PMID- 18318116
TI  - [Association of polymorphous markers Pro72Arg and C(-594)CC OF TP53 gene with
      diabetic polyneuropathy in patients with type 1 diabetes mellitus living in
      Moscow].
AB  - The aim of this study was the search of association of polymorphous markers
      Pro72Arg and C(-594)CC of TP53 gene with diabetic polyneuropathy (DPN) in
      patients with type 1 diabetes mellitus with or without clinical signs of DPN. We
      have found that polymorphous marker Pro72Arg of TP53 gene was associated with DPN
      in Russian patients with type 1 diabetes mellitus living in Moscow. The carriers
      of Arg allele and Arg/Arg genotype had higher risk of DPN development (OR = 1.96;
      CI = 1.32-2.90; and OR = 2.14; CI = 1.23-3.73; relatively). On the contrary, the
      carriage of Pro allele was associated with the lower risk of DPN development (OR
      = 0.51; CI = 0.34-0.76). We have not found any association of polymorphous marker
      C(-594)CC of TP53 gene with DPN in Russian patients with type 1 diabetes mellitus
      living in Moscow.

PMID- 18318117
TI  - [Hydrogen peroxide (H2O2) and methyl-beta-cyclodextrin (MPCD) down regulate
      caveolin expression in human lens epithelial cells (HLECs)].
AB  - Oxidative stimulation induced by hydrogen peroxide (H2O2) on human epithelial
      cells (HLECs) was performed to observe the effects on cell viability, caveolin
      expression, and cholesterol depletion in HLECs caused by methyl-beta-cyclodextrin
      (MbetaCD) was also studied. SRA01/04 HLECs were exposed to H2O2 or MbetaCD of
      various concentrations and durations. We used a 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay to measure the effect of H2O2 on the
      viability of SRA01/04 HLECs. The distributions of caveolins after oxidative
      stimulation were probed by fluorescence microscopy and laser scanning confocal
      microscopy. Immunoblotting was performed to analyze alterations of caveolins
      expression. We observed that the viability of SRA01/04 HLECs under 0.1 mM H2O2
      for 10 min or longer was significantly reduced (*p < 0.05, F = 11.63). Laser
      scanning microscopy showed immunofluorescent caveolins in SRA01/04 HLECs under
      0.1 mM H2O2 for 10 min or longer, caveolins were largely confined to
      intracellular domains. Western blots showed both membrane and total caveolin
      protein (22 kDa) levels in SRA01/04 HLECs treated with 0.1, 0.2, 0.5 or 1.0 mM
      H2O2 for 30 min were significantly reduced, compared with the untreated (*p <
      0.05, F = 6.149, or *p < 0.05, F = 14.489 respectively). In addition, the
      membrane and total caveolin protein level after treated with 0.1 mM (*p < 0.05, F
      = 6.843, or *p < 0.05, F = 7.944 respectively) H2O2 for different durations also
      down regulated. Fluorescence microscopy also showed that phosphorylated caveolin
      1 was distributed near the focal adhesions of the cells. This study concludes
      that the responses of HLECs to oxidative stress may include down regulation of
      caveolin and phosphorylation of caveolin-1 on Tyr14, and that MbetaCD also down
      regulates caveolin while depleting cholesterol in HLECs.

PMID- 18318118
TI  - [The 5' untranslated region of the maize alcohol dehydrogenase gene provides
      efficient translation of mRNA in plants under stress conditions].
AB  - Reduced level of expression of most cell proteins under stress conditions is
      determined by low efficiency of cap-dependent translation of corresponding mRNAs.
      The maize gene encoding alcohol dehydrogenase, adh1, is an example of a gene
      which mRNA is efficiently translated under hypoxia. Using reporter gene assay we
      showed that the leader sequence of adh1 mRNA, provides efficient translation of
      reporter gene gfp in Nicotiana benthamiana cells under hypoxia and heat shock.
      The presence of this leader sequence in 5' UTR of mRNA does not change the level
      of expression in aerobic conditions, but under hypoxia and heat shock the levels
      of reporter gfp expression were reduced about 5-10 fold in the absence of leader
      and remained unaffected in its presence in 5'UTR. We found that this leader
      sequence does not change the level of mRNA stability and does not exhibit
      promoter activity. Consequently, leader sequence acts as translational enhancer
      providing efficient translation of mRNA in plant cells under stress conditions.
      Introduction of this sequence into standard expression cassettes may be used for
      development of new systems of expression of target proteins in plants, efficient
      under stress conditions.

PMID- 18318119
TI  - [Multiadaptor 4.1 and RanBP9 protein family members as putative interaction
      partners for VARP, a Rab21 GTPase guanine nucleotide exchange factor].
AB  - VARP is a novel VPS9 domain-containing protein which acts as a guanine nucleotide
      exchange factor for small GTPases Rab21 and Rab5, regulators of early
      endocytosis. However, the molecular mechanisms underlying VARP activity
      regulation and intracellular localization remain unknown. Using protein
      interaction cloning in yeast we isolated multiadaptor proteins of 4.1 protein
      family and RanBP9 as putative VARP interaction partners. The interactions
      revealed might be important for proper intracellular localization of VARP and its
      functions in early endocytosis.

PMID- 18318120
TI  - [How translation termination factor eRF1 Euplotes does not recognise UGA stop
      codon].
AB  - In universal-code eukaryotes, a single class-1 translation termination factor
      eRF1 decodes all three stop codons, UAA, UAG, and UGA. In some ciliates with
      variant genetic codes one or two stop codons are used to encode amino acid(s) and
      are not recognized by eRF1. In Stylonychia, UAG and UAA codons are reassigned as
      glutamine codons, and in Euplotes, UGA is reassigned as cysteine codon. In
      omnipotent eRF1s, stop codon recognition is associated with the N-terminal domain
      of eRF1. Because variant-code ciliates most likely evolved from universal code
      ancestor(s), structural features should exist in ciliate eRF1s that restrict
      their stop codon recognition. To find out amino acid residues which confer UAR
      only specificity to Euplotes aediculatus eRF1, eRFI chimeras were constructed by
      swapping eRF1 E. aediculatus N-terminal domain sequences with the matching ones
      from the human protein. In these chimeras the MC-domain was from human eRF1.
      Functional analysis of these chimeric eRFI highlighted the crucial role of the
      two regions (positions 38-50 and 123-145) in the N-terminal domain of E.
      aediculatus eRF1 that restrict E. aediculatus eRF1 specificity toward UAR codons.
      Possibly, restriction of eRF1 specificity to UAR codons might have been an early
      event occurring in independent instances in ciliate evolutionary history,
      possibly facilitating the reassignment of UGA to sense codons.

PMID- 18318121
TI  - [Binding of human ribosomal protein S16 with the 18S rRNA fragment 1203-1236/1521
      1698].
AB  - Human ribosomal protein (rp) S16 is a homologue of prokaryotic rpS9 that contacts
      the 16S rRNA region formed by helices H29, H30. H38-40, H41, H43 according to X
      ray crystallography data on the 30S ribosomal subunit. In the present work, we
      report studying interaction of human recombinant rpS16 with a RNA transcript
      corresponding to the region 1203-1236/1521-1698 (helices H28-30 and H41-43) of
      human 18S rRNA, which is homologous to the 16S rRNA region known to bind rpS9.
      RpS16 was shown to specifically bind to the transcript forming a stable complex
      with the apparent dissociation constant of (1.3 +/- 0.1) x 10(-8) M at 20 degrees
      C. Nucleotide residues of the transcript that change their accessibility to
      RNases and modifying chemical probes upon the rpS16 binding were determined by
      enzymatic and chemical footprinting. It was shown that rpS16 causes significant
      enhancement of reactivities of nucleotides C1544 (internal loop of helix H41),
      C1618-U1622 and C1629-A1634 (helix H42), C1521-C1523, U1530, C1532 (helix H30)
      and C1645, C1646, G1648 (helix H43) and protection of nucleotides C1670-A1675
      (helix H43). In the bacterial 30S ribosomal subunit many of those nucleotides of
      16S rRNA that correspond to 18S rRNA nucleotides mentioned above contact rpS9
      amino acid residues.

PMID- 18318122
TI  - [Interaction of 23S ribosomal RNA helices 89 and 91 of Escherichia coli
      contributes to the activity of IF2 but is insignificant for elongation factors
      functioning].
AB  - The non-canonical base-pair C2475/G2529 joins helices 89 and 91 of the 23S rRNA
      in the large subunit of E. coli ribosomes. These nucleotides are located at the
      "crossroads" between the peptidyl transferase center, the sarcin-ricin loop and
      the GTPase-associated center. We probed the functional role of nucleotides
      C2475/G2529 by the mutations C2475G, C2475G/G2529C and deltaA2471/U2479 of 23S
      rRNA. All these mutations had no influence on the elongation factors activity but
      had different effects on the cell growth, 23S rRNA conformation and translation
      initiation. C2475G/G2529C and C2475G mutations led to more or less substantial
      decrease in IF2.GDPNP binding to the ribosomes, and IF2-assisted initiation
      complex formation. Ribosome-dependent GTPase activity of IF2 was enhanced by both
      C2475G/G2529C and C2475G mutations. Mutation deltaA2471/U2479 has no influence on
      IF2.GDPNP binding to the ribosome, but reduces IF2-dependent formation of
      initiation complex and the ribosome-dependent GTPase activity. Thus, the contact
      between helices 89 and 91 is important for efficient IF2 functioning in
      translation initiation.

PMID- 18318123
TI  - [Unstructured regions in elongation factors EF1A from three overkingdom of the
      living world].
AB  - A new characteristic for classification of the Living World which based on the
      ability of amino acid sequences to form unstructured regions that appear as loops
      in their 3D structure is described. Our approach is in principle different from
      RNA and protein phylogenies that are based on the alignment of amino acid
      sequences from different organisms. Introduction of new structural-functional
      characteristic in itself is of undoubted interest because megataxonomy and
      macrophylogeny lack features that may be resolve evolutionary relation between
      different groups of organisms though apparent abundance of such characteristics
      are present. We used the program FoldUnfold to search for unstructured regions in
      the elongation factors EF1A. The reliability of loop prediction was checked
      against five factors whose structure is known from X-ray analysis. In addition to
      two cross-bridges between three structural domains in the elongation factors, the
      program predicts extra loops. Not counting the effector loop that is inherent to
      all factors, there are six. Three (A, B and C) of the six different loops are
      revealed in the first domain, one loop (D) in the second, and two loops (E and F)
      in the third domain of the factor, all six of which are never found in the same
      factor. Signatures of elongation factors for each Superkingdom of the Living
      World have been found for several dozen typical representatives from each
      Superkingdom. These signatures lead to the variation of the number of loops and
      their localization within the factor domains. The obtained data leads us to
      believe that the approach based on the prediction of unstructured protein loops-
      up to six--must have higher resolution than the method based on the indels
      (insertion + deletion), the number of which equals one for the same elongation
      factors. In our analysis, the specificity of sequences it is important, in
      addition to the existence of loops. Since the total number of loops predicted in
      the factors increases with the complexity of an organism, we propose the
      following about the role of the loops in evolution: holding to the principle of
      "thrifty inventiveness", Nature operates with different universal inserts (loops)
      adapting their number and location among the factor domains as well as their
      amino acid composition so that the protein will perform special functions: one in
      protozoa and several in higher organisms.

PMID- 18318124
TI  - [Structure and evolution of mammalian maltase-glucoamylase and sucrase-isomaltase
      genes].
AB  - Maltase-glucoamylase and sucrase-isomaltase are two human glycosidases
      responsible for starch digestion. We have performed a comparative analysis of
      their amino acid sequences from several species of mammals and their orthologues
      from other chordates. This allowed us to determine the evolutionary history of
      the enzymes. Both glycosidases are paralogues and contain GH31 family catalytic
      domains. The common evolutionary precursor of these genes has arisen by a tandem
      duplication. As a consequence, sucrase-isomaltase consists of two homologous
      parts. The maltase-glucoamylase gene was a subject of several additional
      duplications, which number was not the same in different mammals. The locus,
      containing this gene, consists of 4-7 tandem repeats. The amino acid sequence,
      encoded by each of them, is similar to both parts of sucrase-isomaltase.

PMID- 18318125
TI  - [Transcription factor AP-1 components as a psoriasis candidate genes].
AB  - Psoriasis is an autoimmune multifactorial dermatological disease frequently
      occured in European population. As for other multifactorial genetic diseases
      success in psoriasis treatment may be achieved due to determination of molecular
      genetic mechanisms of pathogenesis triggering and psoriasis candidate genes and
      proteins searching as targets for drugs. Using bioinformatic analysis of
      transcriptome data AP-1 transcriptional factor components were revealed as
      psoriasis candidate genes.

PMID- 18318126
TI  - [Comparative analysis of copy number of ID and B1 short retroposons in rodent
      genomes].

PMID- 18318127
TI  - [Receptor specificity of human enteroviruses].
AB  - The review presents the currently available data on the receptor specificity of
      enteroviruses. It discusses whether changes in the receptor specificity of
      enteroviruses may play a role in their in vitro and in vivo reproduction.

PMID- 18318128
TI  - [Mutations of the Epstein-Barr virus LMP1 gene mutations in Russian patients with
      lymphoid pathology and healthy individuals].
AB  - Epstein-Barr virus (EBV) is an etiological agent of a number of benign and
      malignant human diseases, such as infectious mononucleosis (IM), Hodgkin's
      lymphoma (HL), and non-Hodgkin's lymphoma (NHL). EBV latent membrane protein 1
      (LMP1) gene (recognized as a viral oncoprotein) of various clinical and
      geographical origin was found to have different types of amino acid mutations
      affecting its biological activity. Since there was no information on the strain
      differences in LMP1 of EBV persisting in Russia, the authors made a sequence
      analysis of LMP1 samples amplified from the biological materials of Russian
      patients with IM, HL, and NHL and healthy individuals. The studies have shown
      that LMP1 variants of Russian origin are a mixed heterogeneous group containing
      both the earlier characterized and presumably new genetic variants. Among the
      point amino avid substitutions, the mutations S366T, F106Y, 185L, and E328Q
      associated with the enhanced transforming activity of a LMP1 molecule and its
      reduced cytotoxicity. There was no specific association between the certain
      Russian variants of LMP1 and the specific forms of the disease (IM, HL, and NHL).

PMID- 18318129
TI  - [Molecular epidemiology of ECHO 6 virus, the causative agent of the 2006 outbreak
      of serous meningitis in Khabarovsk].
AB  - A total of 3194 cases of enterovirus meningitis were notified in the Russian
      Federation in 2005, of them there were 1434 cases in the Khabarovsk Territory.
      Enteroviruses were isolated from 1020 out of the virologically studied 1362
      patients from the Khabarovsk Territory. Viruses E6 and E30 were isolated in 80
      and 14.7% of cases, respectively. E1, E3, E7, E33, Coxsackie virus B1, B4, B5,
      and A10 were sporadically detected. The E6 strains isolated in Komsomolsk-on-Amur
      were identical while E6 strains isolated in Khabarovsk belonged to two different
      genotypes and greatly differed from those isolated in Konsomolsk-on-Amur. The
      virus E30 strains isolated in Khabarovsk and Komsomolsk-on-Amur had a 1%
      difference in VP1 genome nucleotide sequence and belonged to E30 subtype that
      circulated in Russia and Kazakhstan in 2004-2005.

PMID- 18318130
TI  - [Native and renatured oligomer-dependent epitopes of intracellular influenza
      virus nucleocapsid protein].
AB  - Intracellular NP oligomers have been shown to react with some anti-NP monoclonal
      antibodies (mAbs) in radio-immnoprecipitation, immunoblotting, and dot
      immunoassay. Soluble NP monomers obtained after thermal dissociation of NP
      oligomers are not recognized by mAbs unlike the NP monomers whose concentration
      increased by about 100-fold due to transfer to the nitrocellulose membrane after
      polyacrylamide gel electrophoresis. The findings demonstrated that in the intact
      NP oligomers there were epitopes determined by their quaternary structure. These
      oligomer-dependent epitopes may be renaturated in vitro under the conditions
      allowing for a concentration-dependent NP-NP association.

PMID- 18318131
TI  - [Optimization of the gene composition of influenza H5 virus hemagglutinin
      containing reassortants and their efficacy in immune cross-protection
      experiments].
AB  - The reassortant described in the authors' previous paper contained 6 genes
      originating from the high-yield virus A/Puerto Rico/8/34 (H1N1) and the genes of
      hemagglutinin (HA) and neuraminidase (NA) of the low-pathogenic avian influenza
      A/Duck/Primorie/2621/2001 (H5N2) (6:2 reassortant). The reassortant was used for
      the backcrossing with the parent avian virus in order to optimize the gene
      composition. Genotyping of the highest-yield second-generation reassortment
      indicated that it had obtained the PB1, HA, and NA genes from the virus
      A/Duck/Primorie/ 2621/2001 and the other genes received the genes from the virus
      A/Puerto Rico/8/34 (5:3 reassortant). The yield produced in the embryonated
      chicken eggs by the 5:3 reassortant was higher than that produced by the 6:2
      reassortant although it did not achieve the reproduction of the parent virus
      A/Puerto Rico/8/34. Murine immunization with the inactivated reassortant
      containing the HA and NA genes of the virus A/Duck/Primorie/2621/2001 (H5N2)
      provided an efficient protection against the virus containing HA and NA of a
      recent H5N1 strain.

PMID- 18318132
TI  - [Immunogenic properties of recombinant vaccinia virus containing the human IL-2
      gene].
AB  - A genetic construct of the human interleukin-2 (IL-2) gene within vaccinia virus
      (L-IVP strain) has been designed. The authors show the capacity of CV-1 cells
      infected with the recombinant vaccinia virus VV-SIL2 to secrete human IL-2 into
      the culture medium. Human IL-2 has been detected by immunoblotting. The sera from
      the animals immunized with the recombinant virus VV-SIL2 exhibited both human IL
      2 and its antibodies throughout the observation period. This recombinant virus
      immunization induced both humoral and cell-mediated immune responses to human IL
      2; the observed changes in the concentrations of cytokines are likely to suggest
      that the response predominantly followed a Th1 pathway. The study construct was
      nontoxic at the used concentrations and administration routes. The findings point
      that it is promising to investigate the adjuvant properties of the recombinant VV
      SIL2 vaccine-based preparation for immunization in combination with various
      vaccines and to study this construct in therapy for cancer diseases.

PMID- 18318133
TI  - [Evaluation of the efficacy of wiferon and arbidol in adult influenza].
AB  - The therapeutic efficacy of wiferon (recombinant alpha2beta-interferon) versus
      arbidol was studied in a double-blind controlled study in patients with
      laboratorily verified influenza. Within the first 24-36 hours after the onset of
      the disease, wiferon and arbidol reduced the duration of fever, intoxication, and
      the catarrhal symptoms of the disease as a whole. The agents were shown to have
      an immunomodulating effect.

PMID- 18318134
TI  - [In vitro activity of Russian ribavirin on the models of Crimean-Congo
      hemorrhagic fever virus, Rift Valley fever virus, and Tahyna and Dhori viruses].
AB  - The high activity of ribavirin made by effective biotechnology in Russia was
      established in in vitro experiments using the models Crimean-Congo hemorrhagic
      fever virus, Rift Valley fever virus, and Tahyna and Dhori viruses, which
      suggests that it is promising in using the drug in the treatment of infection
      with these viruses.

PMID- 18318135
TI  - [Study of the diagnostic potential of various regions of tick-borne encephalitis
      virus glycoprotien E].
AB  - Bioinformation techniques were used to analyze envelope glycoprotein of tick
      borne encephalitis virus in order to determine the potential diagnostically
      significant antigenic clusters. Five selected regions of the amino acid sequence
      of protein E were retranslated to nucleic sequences, by employing the optimum
      code for E. coli. The resultant DNA fragments were synthesized by polymerase
      chain reaction from synthetic oligonucleotides and expressed in E. coli cells.
      The recombinant antigen replicating the region from 296 to 414 aminoacids
      demonstrated the most significant antigenic activity. The findings lead to the
      conclusion that this recombinant protein may be considered as a candidate for the
      development of a diagnostic assay.

PMID- 18318136
TI  - [Design of equine serum-based Marburg virus immunoglobulin].
AB  - Immunoglobulin (Ig) against Marburg fever (MF) has been obtained from the equine
      serum. In terms of physicochemical and immunobiological properties, the obtained
      preparation corresponds to the quality of heterologous commercial
      immunoglobulins. The application of Marburg virus (MV) Ig with a titer of no less
      than 1:2048 by the emergency prevention scheme 1-2 hours after intraperitoneal
      inoculation of guinea pigs with MV in a dose of 20-50 LD50 protected 88-100% of
      the animals from death. MV Ig is recommended for emergency prevention of human
      MF.

PMID- 18318137
TI  - [Evaluation of the efficiency of external assessment of the quality of
      determining antibodies to hepatitis C virus in the network of screening
      laboratories].
AB  - A regional external quality assessment (EQA) system for determining anti
      hepatitis C virus (HCV) was developed and introduced. For this, a control panel
      comprising 14 samples with anti-HCV and 6 samples without anti-HCV was tested in
      the reference laboratory of Moscow Infectious Hospital One. A total of 6 sessions
      were conducted with the participation of 8 laboratories. The regional EQA system
      covering a limited number of laboratories was shown to significantly improve the
      quality of detection of hepatitis C virus antibodies. The optimal multiplicity of
      sessions for the developed EQA system was ascertained to be once fortnight. It is
      possible to define the current rating of screening laboratories in the
      sensitivity criterion and to elaborate address organizational-and-methodic
      measures according to the results of control tests.

PMID- 18318138
TI  - [Alkaline cultivation of bovine rotavirus in the continuous cell cultures].
AB  - Alkaline versus neutral cultivation of bovine rotavirus strain 101 in the
      continuous cell cultures resulted in a significant acceleration of a reproduction
      cycle with a very significant cytopathic effect.

PMID- 18318139
TI  - [Comparative assessment of determination of measles virus IgG antibodies in blood
      serum and dried whole blood].
AB  - Enzyme immunoassay (Dade Behring Enzygnost diagnostic kit, Germany) was used to
      estimate the levels of measles virus IgG antibodies in 72 samples of blood serum
      and eluates of the whole blood dried on the Whatman 3M filter paper. The
      sensitivity of the dried blood test was 98.4%. The regression analysis showed a
      high correlation of the results (r2 = 0.89; regression coefficient 0.89). Measles
      virus IgG antibodies were ascertained to be retained in the dried blood at room
      temperature long (for at least 2 years). After 2-year storage at +4 degrees C,
      there was a reduction in the concentration of antibodies; however, they were
      still detectable in 62 (96.9%) out of 64 positive samples. The dried blood test
      is recommended for wide use to study immunity to measles virus.

PMID- 18318140
TI  - [Therapeutic efficacy of 4-(adamantyl-1)-1-(1-aminobutyl) benzene in experimental
      fungal pathology].
AB  - Antifungal activity of an adamantane derivative, i. e. 4-(adamantyl-1)-1-(1
      aminobutyl) benzol was studied in experiments in vivo in a model of generalized
      infection and local skin injury. In doses of 0.1 LD50, 0.001 LD50, 0.001 LD50
      (intraperitoneal administration) it had a therapeutic effect on generalized
      candidiasis and promoted 60-80-percent survival of the laboratory animals. Its
      application as 1-percent ointment to Candida albicans infected skin prevented the
      wound formation in rabbits and showed therapeutic efficacy in the treatment of
      infected wounds in albino rats.

PMID- 18318141
TI  - [Study of antituberculous activity of moxifloxacin conjugate with macrophage
      scavenger-receptor ligand].
AB  - Mycobacterium tuberculosis is an intracellular pathogen that persists in
      macrophages of the human host. An approach to improving the treatment of
      tuberculosis is target delivery of antibiotics to macrophages using ligands to
      macrophage receptors. The antituberculous activity of the conjugate of the
      antituberculous antibiotic moxifloxacin with carboxymethylglucan was studied in
      vitro using the J774 macrophage cell line and peritoneal macrophages. The
      antituberculous activity of the conjugate was higher than of the free
      moxifloxacin. The target antibiotic delivery to macrophage cells in tuberculosis
      infection was shown perspective.

PMID- 18318142
TI  - [Variability of nisin-synthesizing wild strain Lactococcus lactis subsp. lactis
      119 under the effect of ultraviolet light].
AB  - To increase the nisin synthesizing activity of the natural strain Lactococcus
      lactis subsp. lactis 119 isolated from sour milk, UV irradiation in different
      doses was used followed by isolation of productive clones. The highest mutation
      effect was observed with the dose of 76,000 erg/mm2, when 11% of the cells
      increased their productivity by 12.8% at the minimum survival rate. Two-step UV
      irradiation and adaptive selection on the nisin-contaning medium provided
      isolation of a strain with the activity 42.6% higher than that of the initial
      strain (3850 IU/ml). Natural and UV-induced variability of the strain by the
      nisin synthesis, growth rate, carbohydrate consumption and sensitivity to
      antibiotics of various groups were studied.

PMID- 18318143
TI  - [Resistance of experimental antibiotic resistant variants of Yersinia pestis EV76
      (NIIEG line) to modern marker antibiotics].
AB  - Lower susceptibility of previously designed experimental polyresistant variants
      of Yersinia pestis EV76 (NIIEG line) with inserted R plasmid or transposons to
      some present antibiotics efficient in the treatment of plague, i. e. doxycycline,
      amikacin and ceftriaxone, was shown. Clones, more resistant to them vs. the
      initial variants, were selected. They accustomed in vivo in laboratory animals
      per se and after administration of antibiotics. The data on the protective
      activity of the new variants in the treatment of experimental plague after
      combined vaccination and antibiotic prophylaxis are presented.

PMID- 18318144
TI  - [Relative bioavailability and bioequivalence of the antimycotics ketoconazole and
      fluconazole].
AB  - Pharmacokinetics and bioavailability of the antimycotics ketoconazole FPO and
      fluconazole (Russia) and the analogous drugs nizoral (Belgium) and diflucan
      (France) were comparatively studied on animals and in clinical trials. The
      pharmacokinetic parameters of the drugs were determined and their bioequivalence
      was shown (90-110%) that is evident of their therapeutic equality.

PMID- 18318145
TI  - [Antibiotic susceptibility and molecular mechanisms of cephalosporins resistance
      in Klebsiella isolates from patients with hospital-acquired infections].
AB  - Antibiotic susceptibility of nosocomial Klebsiella isolates from inpatients of 30
      medical centres in 15 various regions of Russia was studied. In total 212 strains
      were tested. The Klebsiella genus was represented by the following species:
      Klebsiella pmeumoniae ss. pneumoniae (182 isolates, 85.8%), Klebsiella pneumonia
      ss. ozaenae (1 isolate, 0.5%), Klebsiella oxytoca (29 isolates, 13.7%). The
      susceptibility was determined by the broth microdilution method. Carbapenems
      (imipenem and meropenem) remained to be the most active antibacterial agents.
      However, 1 imipenem resistant strain and 2 meropenem resistant strains were
      isolated. As for the 3rd generation cephalosporins, the lowest MICs were observed
      with the use of the inhibitor-protected agents, such as ceftazidime/clavulanic
      acid (MIC50 0.25 mcg/ml, MIC90 64 mcg/ml). 48.8%, 16.9%, 29.7% and only 10.5% of
      the isolates was susceptible to cefepime, cefotaxime, ceftazidime and
      cefoperazone respectively. Detecting of the beta-lactamase genes (TEM, SHV and
      CTX) was performed by PCR in 42 strains of Klebsiella pneumoniae ss. pneumoniae.
      Alone or in various combination the TEM type beta-lactamases were detected in 16
      (38.1%) isolates. SHV and CTX were detected in 29 (69%) and 27 (64.3%) isolates
      respectively. Combinations of 2 and 3 different determinants of resistance to
      beta-lactams were revealed in 23.8% and 26.2% of the isolates respectively. No
      isolates producing class B MBL among the carbapenem resistant nosocomial
      Klebsiella strains were detected.

PMID- 18318146
TI  - [Prophylaxis of wound infection in patients with head and neck tumors with an
      account of the pathogen taxonomic pattern].
AB  - The most important problem of onkology, i. e. antibiotic prophylaxis and
      treatment of postoperative infectious complications is touched upon in the paper.
      The current publications on the problem are discussed and the autors' experience
      on the treatment is described. The spectrum of the main pathogens of wound
      infections in patients with head and neck tumors is considered.

PMID- 18318147
TI  - [Analysis of the efficacy of various regimens of antibacterial therapy in
      inpatients with community-acquired pneumonia].

PMID- 18318148
TI  - [Survey of pharmacoeconomic studies on the problem of drug resistant
      tuberculosis].

PMID- 18318149
TI  - [The pathogenetic role of the serotonin-histamine-cyclic nucleotide system in
      ulcerogenesis].
AB  - The study was dedicated to the role of serotonin in the development of
      experimental gastric ulcer in rats, and the role of serotonin, histamine, and
      purine bases in patients with peptic ulcer. The intensification of serotonin and
      histamine production was shown to promote the sanogenesis of persistent gastric
      ulcer.

PMID- 18318150
TI  - [Endocrine-genotoxic switchings as promoter of main noninfectious diseases].
AB  - Peculiarities of the incidence and spread of main non-infectious diseases (MNID)
      are in one or another way connected with the conception of "normal" and
      "successful" aging. The age-related increase in the frequency of MNID, associated
      with estrogen deficiency or excess, can be explained by the presence of estrogen
      effect switching phenomenon. The increase in the genotoxic effect of estrogens,
      isolated or combined with the weakening of the hormonal effect, can worsen the
      clinical course of MNID (including malignant tumors of hormone-dependent
      tissues). The effects of two other endocrine-genotoxic switchings (the joker
      function of glucose and adipogenotoxicosis) may realize in the same direction.
      The three mentioned phenomena form the so called basic triad, separate elements
      of which can interact. Endocrine-genotoxic switchings and their inductors are
      targets for prophylactic measures and, possibly, therapeutic ones. Both
      approaches may be divided into several groups with different points of
      application, whereas their ultimate goal is optimal balance between hormonal and
      DNA-damaging effects of estrogens, glucose, and adipose tissue-associated
      factors.

PMID- 18318151
TI  - [Cytogenetic and other cariological parameters of exfoliative buccal cells in
      Vietnamese children from areas where dioxin-containing herbicides were applied].
AB  - In a cohort of 69 South Vietnam children, full cariological analysis of buccal
      epithelial cells was performed. In order to evaluate the significance of
      cariological changes, all the parameters under study were divided into three
      groups: cytogenetic indices, apoptotic indices, and indirect indices of
      proliferation; integral indexes in each group were determined and the relations
      between them were found while assessing the effects of environment pollution on
      public health. The number of cells with cytogenetic alterations (micronuclei and
      protrusions) was increased, the process of tissue proliferation was intensified,
      and the apoptotic process was decelerated in children li-ing in areas polluted
      with Agent Orange/dioxins, which evidenced that the complex of environmental
      factors these superecotoxicants were part of had a harmful effect on the
      population. The parameters studied did not depend on age and sex of the children;
      the number of congenital morphogenetic variants per one child significantly
      correlated with the sum of cells with cytogenetic alterations.

PMID- 18318152
TI  - [The role of food factor in the forming of the variety of the characteristics of
      fecal microbiocenosis in rats].
AB  - The researchers studied mechanisms of the forming of fecal microbiocenosis in
      rats on different diets. The composition of nutritional elements had a
      significant effect on the qualitative and quantitative composition of both
      indigenous and transitory fecal microflora. Under scant diet, the leading role in
      the forming of intestinal microbiocenosis belonged to macroorganism
      characteristics, while under excessive nutrition intestinal microbiocenosis
      depended mostly on the composition of the dietary intake. The study found that
      excessive nutrition lowered competition for the nutrition substrate, and
      indigenous microflora no more prevented the growth of transitory one.

PMID- 18318153
TI  - [The response of high school students' visual system in a model experiment with a
      wide scope of variants of information display].
AB  - In order to develop hygienic standards for information view on a personal
      computer display, a model (laboratory) experiment on high school students was
      performed. A wide scope of variants of information display (15 color combinations
      of alogical tests consisting of 7000 symbols vs. reading from a sheet of paper)
      was used, and the response of the visual system was studied. The response of the
      viewers was assessed according to reading speed taking into account the number of
      mistakes, which made it possible to determine visual task complexity for each
      variant of the test. The second parameter under study was mistake dynamics,
      counted according to the number of mistakes per each thousand of symbols read.
      The data obtained demonstrated that to high school students reading a PC monitor
      was a significantly more difficult visual task than reading a sheet of paper. The
      following color combinations on the computer display were most favorable: blue
      text on a yellow background, yellow text on a blue background, and red text on a
      green background.

PMID- 18318154
TI  - [The Saint-Petersburg summit of Group of Eight: the problems of infectious
      diseases and the ways of their solution].
AB  - In 2006, being the presiding country at the Group of Eight Summit for the first
      time, Russia proposed the issue of counteraction with infectious diseases as one
      of the priority issues. In addition to the realization of the priority National
      Health Project, which is to a large degree dedicated to the immunoprophylaxis of
      infectious diseases as well as the prevention and treatment of HIV-infection/AIDS
      and hepatites B and C, a meeting of the Presidium of Russian Federation State
      Council presided by President V. V. Putin, dedicated to the problem of HIV
      infection epidemic spread, was held on April 21; the meeting resulted in the
      formation of Governmental Commission on the problems of HIV-infection/AIDS. On
      July 16, the leaders of Group of Eight during their meeting in Saint-Petersburg,
      discussed and validated the Declaration on counteraction with infectious
      diseases, reflecting the position of the leaders on the entire complex of
      problems connected with the spread of infectious diseases, and determining the
      main principles of the global strategy of counteraction with epidemics under the
      threats associated with the appearance of new infections, such as avian
      influenza, HIV-infection/AIDS, tuberculosis, and malaria. While preparing for the
      Summit, Russia made a range of suggestion aimed mostly on the reinforcement of
      possibilities to control infectious diseases in Eastern Europe and Central Asia.
      Practically all Russia's initiatives were supported by the partners, which was
      also reflected in the conclusive document of the Summit. Following Russian
      initiatives, Group of Eight intends to increase the effectiveness of
      international affords on the prevention and elimination of the consequences of
      natural disasters, including the use of fast response teams. To provide Russia's
      contribution to this initiative, modernized specialized antiepidemic teams will
      be used. Taking into consideration the present-day financial participation of
      Russian Federation in the realization of international programs on counteraction
      with infectious diseases, Russia is gradually leaving the status of a recipient
      country and becomes a donor of international financial aid.

PMID- 18318155
TI  - [Chaperones and their role in atherogenesis].
AB  - The combination of HSP60-specific humoral and cellular reactions is handled as
      the new diagnostic sign, reflecting the risk of the development of
      atherosclerosis, which is independent of other classic risk factors. Chaperones
      are identified as important pathogen-related antigens used to design vaccines
      against atherosclerosis. The high evolutionary homology of HSPs raises the issue
      on the safety of such vaccines.

PMID- 18318156
TI  - [The role and biological significance of toll-like receptors in the anti
      infectious resistance of the organism].
AB  - Modem conceptions of the role of toll-like receptors (TLR) in the innante
      immunity mechanisms realization and data on the interaction between TLR and
      pattern-associated molecular proteins of microbial or endogenic origin are
      presented in the review.

PMID- 18318157
TI  - [Endothelial changes in cardiovascular pathology in the elderly. Part 2. Signal
      molecules and the pathogenesis of atherosclerosis].
AB  - This article is a continuation of the review on the issue of the interaction
      between the endothelium and numerous biologically active substances, secreted by
      endotheliocytes and their environment--the so called signal molecules--in the
      most prevalent cardiovascular pathology in the elderly. For example tumor
      necrosis factor plays a pathogenetic role as an immunomodulator, possesses anti
      inflammatory and pro-atherogenic properties, provokes endothelial dysfunction,
      and stimulates the expression of other pro-inflammatory cytokines. Other signal
      molecules are described as well. The article also presents data from studies
      directed towards the perfection of atherosclerosis therapy via affecting signal
      molecules: depression of the expression of interleukins and their receptors,
      inhibition of atherogenic interleukins, neutralization of pro-inflammatory
      interleukins, and introduction of interleukin receptor antagonists.

PMID- 18318158
TI  - [Clinical diagnostics of papillary fibroelastoma].
AB  - Papillary fibroelastoma (PFE) is a benign heart tumor, the diagnosis of which is
      difficult. Clinical manifestations of PFE are non-specific and scarce, and for
      this reason the tumor is often revealed during a heart surgery of an autopsy. PFE
      affects patients of all ages from neonates to 96-year-old ones and is often
      localized on valvular cusps, although vegetations may appear on other
      intracardiac structures. The histogenesis of the tumor is unclear; there are
      several theories of PFE origin (hemodynamic effects on the myocardium, viral
      theory, iatrogenic theory etc.) Macroscopically the tumor is small size, villous,
      whitish-grey, consists of a pedicle and villi of gely-like soft or dense-elastic
      consistence. The mobility of the tumor and the fragmentation of its tissue lead
      to its main complications such as obstruction of cardiac cameras (in-flow and out
      flow disorders) and embolic syndrome in various basins (the brain, coronary
      arteries, the eye, the kidneys, and the lungs). The diagnosis of PFE is made
      using EchoCG, preferably transesophageal one. Treatment of PFE is surgical and
      consists of tumor or cusp removal. PFE should be differentiated from other benign
      and malignant heart tumors, infective endocarditis, heart echinococcosis,
      coronary artery disease, and cerebrovascular diseases.

PMID- 18318159
TI  - [Population models in the study of neurogenic domnants of arterial hypertension.
      Report 2. The peculiarities of arterial hypertension matched with personal
      motivational priorities].
AB  - The peculiarities of primary arterial hypertension in persons with opposite types
      of motivational priorities were studied. The features and prevalence of the
      disease in two populations were analyzed. Group 1 consisted of 141 subjects whose
      profession and working conditions required maximum realization of the market
      oriented motivational dominant ("socially active persons"); Group 2 consisted of
      147 "altruistic" type subjects who lacked the first group's motivational
      dominant. The study found a higher prevalence of the disease and a lower level of
      psychological health as part of quality of life in Group 1 (p = 0.018); the
      disease in this group was more intensive and significant structural and
      functional left ventricular transformation was typical. The absence of pernicious
      habits and healthy life-style should not be considered primary factors of a more
      favorable clinical course of the disease in the "altruistic" group.

PMID- 18318160
TI  - [Multifactor stress-echocardiography in the diagnostics of coronary artery
      disease at the pre-hospital stage].
AB  - The aim of the study was to assess tolerance to and the appropriateness of multi
      factor stress-echoCG for the diagnostics of initial stages of coronary artery
      disease (CAD) in out-patient practice. The subjects of the study were 25 men aged
      32 to 51 (mean age 43.2 +/- 4.9 years). Of these patients, 10 men with heartache
      were suspected to have CAD, and 15 suffered from stage II essential hypertension
      (EH). In five patients (including four with stage II EH) chest pain which was
      untypical for stenocardia, was observed, and in five other patients rare attacks
      of class lexertional stenocardia took place. All the patients underwent stress
      echoCG with a combination of two stress agents: transesophageal left ventricular
      cardiostimulation (TEES) and dipiridamol test (DP). Stress echoCG was positive in
      eight (32%) of the patients including seven subjects with stenoses of less than
      50% of anterior interventricular artery (AIVA) diameter and one patient with
      stenoses of 50 to 70% of AIVA diameter. Of these patients, 20% (n = 5) had stage
      II EH. There were no complications or undesirable reactions. The method of
      multifactor stress-echoCG allowed for the early diagnosis of CAD in 32% of
      patients, in whom conventional functional diagnostic techniques were of little
      informative value, including the 20% of patients with stage II EH. Thus,
      multifactor stress-echoCG (DP+ TEES) is an approachable, informative, and safe
      method of early CAD diagnostics, which may be recommended for wide application in
      outpatient departments for a rational selection of patients for further CG and
      planning therapeutic tactics in CAD patients.

PMID- 18318161
TI  - [The efficacy of complex therapy of ventricular arrhythmias with emoxipin and
      preductal in combination with antiarrhythmic agents].
AB  - Forty-five patients with coronary heart disease and various forms of ventricular
      arrhythmias (25 men and 20 women aged 42 to 73) were examined. The use of complex
      therapy with emoxipin and preductal in a combination with antiarrhythmic agents
      potentated the action of these preparations. The application of emoxipin resulted
      in a longer positive effect.

PMID- 18318162
TI  - [The peculiarties of nitric oxide synthesis in patients after coronary bypass
      surgery].
AB  - Nitric oxide (NO) participates in many physiological processes including those
      taking place in the cardiovascular system. The peculiarities of NO synthesis in
      patients after coronary bypass surgery were studied. The systems of NO generation
      responded in different ways. Changes in the levels of end-products of NO
      metabolism may be used as an additional prognostic criterion of the course of the
      postoperative period. The study found a direct correlation between the levels of
      end-products of NO metabolism and left ventricular ejection fraction as well as a
      reverse correlation between the level of end-products of NO metabolism and
      atherogenic lipids.

PMID- 18318163
TI  - [Neutrophile apoptosis in patients with chronic rheumatic heart disease].
AB  - The purpose of the investigation was to study peculiarities of the functioning of
      neutrophile granulocytes in chronic rheumatic disease (CRD) complicated by
      cardiovascular pathology. The subjects of the study were 80 patients with CRD of
      the heart with valvular defects, accompanied by arterial hypertension (AH) and
      cardiac arrhythmias: 37 men (mean age 53.6 +/- 9.7 years) and 43 women (mean age
      56.2 +/- 9.6 years). The control group consisted of 25 healthy donors. Isolated
      peripheral blood neutrophiles were cultivated during 6 hours. The level of nitric
      oxide (NO) production was measured. Functional cell activity was studied by
      chemoluminiscent assay. The degree of apoptotic readiness was studied by
      immunocytochemical method, determining bak marker expression on cell membrane
      surface. In CRD the processes of oxygen-dependent neutrophile metabolism were
      found to be intensified, which was accompanied by intensified reserve abilities
      and decreased NO synthesis and apoptotic activity. Functional cell activity in
      patients with a background of AH was characterized by lowered granulocyte NO
      production. Intensified production of active oxygen metabolites, observed in
      paroxysmal cardiac fibrillation, evidences the hyperactivity of the pro-oxidative
      system, leads to fast myocardial cell membrane lesion and the development of
      structural changes forming abnormal automatism and trigger activity. Neutrophiles
      isolated from patients with CRD were in a state of priming, the feature of which
      was high biocide cell potential. The lowering of apoptotic readiness evidences
      high mobilization abilities of neutrophiles. The synthesis of NO as one of
      autoregulation factors is a protective mechanism directed against the cytotoxic
      activity of phagocytes. The stimulation of granulocyte NO production can lower
      the oxidative stress intensity and leukocyte aggression and stabilize the course
      of the disease.

PMID- 18318164
TI  - [The activity of Willebrand factor--glycoproteins IIb/IIIa complex in patients
      with coronary and low extremity arterial atherothrombosis and type 2 diabetes
      mellitus].
AB  - A lot of attention has been paid lately to the study of risk factors of
      cardiovascular diseases in patients with diabetes mellitus type 2 (DM2). Numerous
      investigations have revealed a connection between the intensity of thrombus
      formation and carbohydrate exchange disturbances. In the present paper, the
      dependence of the levels of Willebrand factor--glycoproteins IIb/IIIa complex on
      the clinical forms of coronary artery disease (I-II functional class stenocardia;
      old myocardial infarction) and lower limb ischemic disease (intermittent
      claudication) in patients with DM2 were studied. The comparison group consisted
      of DM2 patients without clinical manifestations of coronary artery disease or
      lower limb ischemic disease; the control group consisted of practically healthy
      individuals. The study found that the level of Willebrand factor--glycoproteids
      IIb/IIIa complex was significantly higher in all DM2 patients vs. healthy
      controls.

PMID- 18318165
TI  - [Hemodynamic types in arterial hypertension, and their changes under physical
      exercise].
AB  - Mismatch between the volume of blood entering the arterial circulation and the
      capacity of the latter presents the direct cause of arterial hypertension (AH),
      regardless its ethiology and pathogenesis. In most cases, it results from
      arteriolar spasm and increased blood flow resistance, or with increased cardiac
      output, which determines the type of hemodynamics. The aim of this investigation
      was to study central and peripheral hemodynamics in AH as well as to assess
      cardiovascular system reactivity under graduated physical exercise taking into
      account the type of hemodynamics and examinees" age. One hundred and nine
      patients aged 18 to 40 years with stage I to II AH were examined; 32 young
      healthy volunteers constituted the control group. All the subjects underwent
      veloergometry; vascular wall condition and hemodynamics were studied by volume
      compression oscillometry. The study found that in young AH patients hyperkinetic
      hemodynamic type prevailed; mismatch between arteriolar passability and increased
      cardiac output was obvious, which demonstrated that pathological changes in
      microcirculation were primary, while the tone of large vessels had not changed
      yet. AH patients with the hypokinetic variant of hemodynamics were most
      intolerant to physical load. The study also revealed that an excessive blood
      pressure response during veloergometry was more frequent in older patients (30 to
      40 years).

PMID- 18318166
TI  - [The characteristics of left ventricular myocardial remodeling in patients with
      chronic renal disease, and the effects of spironolactone therapy].
AB  - The work reflects modern concepts of the pathogenesis of myocardial and vascular
      remodelling in a chronic renal disease. Types of changes in left ventricular
      geometry and the condition of the diastolic function in patients at pre-dialysis
      stage of a chronic renal disease and patients on program hemodialysis. Dynamic
      changes in left ventricular parameters under the influence of therapy with
      spironolactone, an aldosterone receptor blocker, are described. The use of
      spironolactone in a dose of 25 mg per day is shown to regress myocardial
      hypertrophy in anuric patients on hemodialysis.

PMID- 18318167
TI  - [Arthrosonography as a method to assess the degenerative and inflammatory
      components of knee osteoarthrosis].
AB  - Ultrasound examination of the knee joints was performed in 254 patients with
      Kellgren-Lawrence I to III stage osteoarthrosis using Aloha Pro Sound 5500 device
      (Japan) and Philips Envision device with 7.5 to 12 MHz linear sensors. Bone
      contours, the height of the cartilage, the degree of the marginal osteophytosis,
      the structure of periarticular formations--the bursae, the tendons and their
      vaginas--as well as the presence and the quantity of articular excaudate, the
      thickness and changes in the synovian membrane, were evaluated. The degree of
      marginal osteophytosis detected by ultrasonography in manifest osteoarthrosis was
      in a direct correlation with the radiological picture. A decrease in cartilage
      height is an ultrasonographic sign of osteoarthrosis, while detailed evaluation
      of the stage of the degenerative process using ultrasonography should be based
      upon the revealing and evaluation of osteophytosis. An increase in the thickness
      of the knee joint synovian membrane by more than 2 mm according to ultrasound
      examination in case of prolonged secondary synoviitis evidences both the presence
      of an inflammatory process and the length of the osteoarthritic disease.

PMID- 18318168
TI  - [Lipid peroxidation in patients with epidemic parotitis complicated by
      pancreatitis].
AB  - The serum concentrations of diene conjugates (DC) and malonic dialdehyde (MDA)
      were measured in patients with epidemic parotitis (EP) complicated or not
      complicated by acute pancreatitis (AP). Forty-eight patients with EP were
      examined. Group 1 consisted of 30 patients with EP complicated by AP; Group 2
      consisted of 18 patients with non-complicated EP. The serum samples from 21
      healthy donors were used as controls. DC and MDA concentrations were measured
      after first clinical signs of AP (days 5th to 8th) appeared and before discharge.
      Serum samples from patients without AP were taken also on days 5th to 8th and
      before discharge. Lipid peroxidation (LP) proved to be activated in patients with
      EP, and in patients with complicated EP the increase in the concentration of
      primary LP products (DC) and intermediate (MDA) LP products was greater.

PMID- 18318169
TI  - [The effectiveness of ascorbic acid and emoxipin in treatment of infiltrative
      pulmonary tuberculosis].
AB  - The aim of this prospective placebo-controlled randomized study was to assess the
      effectiveness of ascorbic acid or emoxipin in the regimen of the therapy of
      infiltrative pulmonary tuberculosis. Emoxipin vs. ascorbic acid favored the
      eradication of tuberculosis mycobacteria. Both preparations decreased the blood
      level of the contra-inflammatory cytokine tumor necrosis factor-alpha (TNF
      alpha), shortened time to the closure of degeneration cavities in tubercular
      infiltrations, decreased the risk of the development of destructive forms, and
      lowered the need for surgical interventions for infiltrative pulmonary
      tuberculosis.

PMID- 18318170
TI  - [On the issue of the diagnosis "boundary arterial hypertension"].
AB  - Many-year observation of patients with arterial hypertension revealed that late
      diagnosis of the initial stage of the disease was typical. Time elapsed from the
      first medical record of an arterial pressure (AP) of higher than 140/90 mmHg to
      the moment the diagnosis of arterial hypertension was made was 4.5 +/- 1.6 years
      in 16 out of the 198 subjects. The authors offer new criteria for the diagnosis
      of boundary arterial hypertension based on 24-hour AP monitoring (unfavorable
      type of 24-hour AP profile) and veloergometry (hypertensive response to physical
      load). Active screening for boundary arterial hypertension based on instrumental
      examination is recommended, and an algorithm for its search is offered.

PMID- 18318171
TI  - [Fecal oncomarkers in the diagnostics of colorectal cancer].
AB  - Colorectal cancer (CRC) presents one of the central problems in modern medicine.
      In approximately every third patient, colon cancer is revealed at stage IV, which
      determines the patient's outcome. Early diagnosis is possible only at the pre
      clinical stage. To find a cheap and non-invasive diagnostic method which would
      determine indications to endoscopy is an important task of modern medicine. The
      authors studied what benefits in CRC diagnostics were provided by fecal
      calprotectin test and different methods for detection of occult blood in feces as
      well as combinations of these. The study found that calprotectin test and
      immunochemical test were more sensitive than hemocult-test for CRC diagnostics (p
      < 0.05). Immunochemical occult blood test proved to be more sensitive for the
      detection of polyps or any kind of colon dysplasia (p < 0.05). Hence, despite its
      relatively high cost, immunochemical occult blood test may be recommended as a
      non-invasive colorectal cancer marker in individuals with moderate risk, while
      fetal calprotectin test, being cheap and easily repeatable, may be used for
      screening only in patients with a high risk of CRC development. Combined
      application of tests for occult blood and calprotectin in feces makes it possible
      to increase the sensitivity of the method up to 97.2%, its specificity up to
      93.3%, and its effectiveness up to 95.6% in the detection of CRC.

PMID- 18318172
TI  - [Aortal regurgitation and atrioventricular block III in Wegener's
      granulomatosis].
AB  - The article presents a clinical observation of a female patient suffering from
      Wegener's granulomatosis with a rare variant of cardiac involvement--a
      combination of an aortal valvular disease (aortal regurgitation) and total
      atrioventricular blockade--who later underwent pacemaker implantation. The direct
      cause of the lethal outcome in this patient was destructive pancreatitis. Data
      from Russian and foreign literature on cardiac pathology in patients with
      Wegener's granulomatosis are analyzed.

PMID- 18318173
TI  - [The juridical significance of primary medical documentation].

PMID- 18318174
TI  - [The effect of dopaminergic nigrostriatal system on sleep deprivation in rats].
AB  - The analysis of the electrophysiological features of sleep-wakefulness cycle in
      Wistar rats for 9h after a 6h sleep deprivation was carried out. The delay of
      sleep rebound (since 2.5-3 h after deprivation) was found in the form of moderate
      increasing of slow-wave sleep and fast-wave sleep phases. According to these
      sleep-wakefulness cycle changes, a quantitative immunohistochemical study of
      tyrosine hydroxylase: a key enzyme of dopamine synthesis--and D1 and D2 receptors
      in nigro-striatal projections has been performed. After sleep, an elevation of D1
      receptors immunoreactivity in caudate nucleus and reduction of tyrosine
      hydroxylase immunoreactivity in compact part of substancia nigra was found. After
      postdeprivation sleep, a decrease of D1 receptors immunoreactivity and increase
      of D2 receptors immunoreactivity in caudate nucleus together some increase of
      tyrosine hydroxilase immunoreactivity in substancia nigra compacta has been
      observed. These data can testify about active role of dopaminergic nigrostriatal
      system which provide at the same time with another neurotransmitters of the
      central nervous system the telencephalo-diencephalic interaction in sleep
      wakefulness-sleep cycle.

PMID- 18318175
TI  - [Dependence of behavioral responses form during shake-off conditional reflex on
      laterality of the neocortex].
AB  - Pattern of discharges and interhemispheric interaction of parietal neurons
      (somatosensory presentation of the ear) were compared in interstimulus intervals
      before active shake-off and passive freezing reactions at stimuli after
      elaboration defensive avoid reflex. Before passive reactions in contrast to
      active right-side influences on left-side neurons were reinforced with delay to
      100 ms, it result in appearence of asymmetry in interhemispheric interaction with
      right-side dominance. Before passive reactions intensity of delta-frequencies was
      increased in impulsation of single neurons and in interaction of cells pair. On
      this evidence the pattern of interhemispheric asymmetry before stimuli can be one
      of a number of factors, determinant active or passive form of behavioral
      reactions and also reflective of activation level of neocortex.

PMID- 18318176
TI  - [Activity balance in behavioural inhibition and behavioural approach systems and
      rest blood pressure in humans].
AB  - The study determined the contribution of activity balance of the two motivational
      systems, i.e. appetitive and defensive, into mechanisms of blood pressure (BP)
      regulation in humans. Average age of participants was 30.29 +/- 9.8 years. Men
      having the BP within normal range and the individuals with firstly diagnosed
      increased arterial blood pressure up to abnormal values were selected. Using the
      method of emotional modulation of the startle reflex (EMSR) by different profiles
      of the EMSR. The participants with shifted balance toward enhanced activity of
      defensive system (amplified probe startle by unpleasant context) or shifted
      balance toward low activity of appetitive system (decrease or inhibition of the
      probe startle by pleasant context) had significantly increased BP in resting.
      Putative mechanisms of the revealed phenomena are discussed.

PMID- 18318177
TI  - [The role of endogenous bioregulators in formation of cardiogenic reflex effects
      on circulation].
AB  - The possible role of endogenous endothelium-derived bioactive substances in
      organization of cardiogenic depressor reflexes under cardiac receptor stimulation
      (by veratrine and bradykinin) was investigated in acute experiments on
      anesthetized rats. The results have shown that endothelium-derived bioactive
      substances take part in forming of the cardiogenic depressor reflex humoral
      components of nervous response or nervous modulators. These data contribute to
      understanding of the role of endogenous endothelium-derived bioactive substances
      (prostacyclin) and different NOS isoforms in mechanisms of depressor reflex
      development and species differences in their involvement in reflex vasomotor
      reactions.

PMID- 18318178
TI  - [Red blood cell aggredation: mechanisms, adrenergic regulation].
AB  - Red blood cell aggregation is a complex multiple-factor process and exerts a
      substantial effect on realization of basic blood function: oxygen transport.
      Insufficient knowledge about mechanisms of erythrocyte aggregation in normal
      conditions and, especially, in pathological conditions, complicates the control
      and correction of possible negative consequences of this process. On addition,
      red blood cell aggregation process is a suitable model for the elucidation of
      basic patterns of intercellular interactions. The paper presents contemporary
      data on mechanisms of erythrocyte aggregation and contribution of plasma and
      membrane erythrocyte properties to this process. Currently available data on
      intracellular signal pathways are discussed.

PMID- 18318179
TI  - [The number of the rat peritoneal cells in normal condition, blood loss, and
      under colchicine injection].
AB  - The modification of peritoneal cells derivation method proposed for the
      peritoneum rat, and the absolute amount of peritoneal lymphocytes, monocytes,
      macrophages, stem and polymorphonuclear neutrophyles, mat cells was determined.
      The procedure of acute 2% blood loss was found to reduce the total amount of the
      peritoneal cells due to depletion of lymphocytes accompanied by an increase in
      amount and proliferative activity of monocyte peritoneal cells, stem neutrophiles
      appearance in the peritoneal cavity. The subcutaneous injection of colchicine
      solution reduces the number of the peritoneal macrophages in normal rats,
      decreases the number of the monocytes, polymorphonuclear neutrophiles and led to
      disappearance of the stem neutrophiles on the second day of blood loss.

PMID- 18318180
TI  - [Effects of acute and chronic introduction of fluoxetine on anxiety-depressive
      condition of male and female mice].
AB  - The effects of acute and chronic fluoxetine treatment in intact and anxiety
      depressive male and female inbred mice of the C57BL/6J strain were studied. The
      gender differences in the behaviour of mice in the tests estimating anxiety,
      locomotion and exploration activity, communication, and depressive-like state
      after fluoxetine injection were established. The dependence of fluoxetine
      treatment on normal or pathological state in mice was discovered. It was
      concluded that use of the animals in pathological condition and chronic (but nor
      acute) fluoxetine treatment are represented as the most correct estimative means
      of antidepressant efficiency.

PMID- 18318181
TI  - [Developmental peculiarities of gas transporting system in chick embryo under
      respiratory surface restriction].
AB  - The half of the chick eggshell surface was covered by the gas-proof layer on the
      11th day and the incubation was continued up to the 14th day. The histological
      investigation of the chorioallantoic membrane after three days of experiment
      revealed that the blood vessels reduction in the covered part was completely
      compensated for by vessel dilatation and the growing in the mesodermal layer of
      intact part with parallel reorganization and dilation of capillary network on its
      surface. The blood gas capacity increase was supported for by haematocrit and
      haemoglobin growth and erythropoiesis stimulation. Cardiac work intensification
      was provided with the left ventricular myocyte hyperplasia and accelerated
      differentiation. The coordinated mobilization of all branches of gas transporting
      system compensated for surface half diminution to maintain the normal metabolic
      level in embryo during 11-14th days of incubation.

PMID- 18318182
TI  - [Response of glycine and glycyl-L-valine uptake parametrs across in vitro everted
      sacs of chicken gut to variations in oxygenation rate and fasting].
AB  - Energy-dependent accumulation of glycine and glycyl-L-valine within the small
      intestinal mucosa in a chicken model of in vitro local oxygenation of the small
      intestinal preparation was studied. It has been shown that the most effective
      bilateral oxygenation significantly increase accumulation of glycyl-L-valine in
      the proximal segment as compared to that under oxygenation only from serosal
      surface both in the fed and 24-hour fasted chickens, whereas in other segments
      these differences was less apparent. This may be due to increased H+/ peptide
      cotransporter expression in the proximal segment. Thus the bilateral oxygenation
      probably may turn on an additional amount of already existing (but non-functional
      during serosal oxygenation) H+/ peptide co-transporters. Moreover, low glycine
      transporter expression may be the reason why supplemental oxygen (bilateral
      oxygenation) has no effect on glycine accumulation in the distal segment of fed
      chickens. A 48-hour fasting decreases glycyl-L-valine accumulation in the
      proximal (and medial) segments, possibly due to progressive decrease in villus
      height. It is concluded that: a) the accumulation rate of glycine was greater
      when presented as the glycyl-L-valine than when presented as the equivalent
      amount of free amino acid; b) the rates of accumulation of glycyl-L-valine are
      highest in the proximal segment, decrease in the medial segment and are the
      lowest in the distal segment; c) the serosal oxygenation is less effective than
      the mucosal and bilateral oxygenation, which markedly stimulates accumulation of
      nutrients in the intestinal mucosa; d) a 24-hour fasting increases glycyl-L
      valine accumulation in the proximal segment only, while glycine uptake was
      increased in the distal segment.

PMID- 18318183
TI  - [Cells give preference to potassium compared to sodium: possible reason of
      alternative choice].

PMID- 18318184
TI  - [Bibliographical analysis of I.P. Pavlov's scientific publications].

PMID- 18318185
TI  - [Anticonvulsant effects of levetiracetam on audiogenic epileptiform siezures in
      Krushinsky-Molodkina rats].
AB  - The new antiepileptic drug levetiracetam (LVT) at doses of 40 and 80 mg/kg
      exhibits a pronounced anticonvulsant effect, influencing all the parameters of
      audiogenic epileptiform seizures (AES) in Krushinsky-Molodkina (KM) rats. The
      latent period of the motor reaction was increased 3-15 times compared to control,
      and the intensity of single convulsive episodes was significantly decreased.
      Changes were also detected in the profile of the first stage of motor activity,
      and the "two-wave" reaction was observed in 50-80% of animals. The mechanism of
      LVT anticonvulsant action in KM rats is probably associated with an increase in
      the inhibitory and a decrease in the excitatory processes in the CNS.

PMID- 18318186
TI  - [Changes in proline-specific peptidase activity in experimental model of
      retrograde amnesia].
AB  - Changes in proline-specific peptidase activity in the frontal cortex and
      hippocampus were studied using the experimental model of retrograde amnesia in
      rats. In one group, the amnesia was produced by a single injection of M
      cholinergic antagonist scopolamine and the other group received the maximal
      electroconvulsive stimulation (MES). The amnesic effect was evaluated in passive
      avoidance test. In the amnesia models under consideration, the activity of
      prolylendopeptidase was significantly increased in both frontal cortex and
      hippocampus. The activity of dipeptidyl peptidase IV was significantly decreased
      in the cortex, whereas in the hippocampus it remained unchanged. Pyracetam
      inhibited prolylendopeptidase in the cortex and hippocampus, whereas dipeptidyl
      peptidase IV activity remained unchanged.

PMID- 18318187
TI  - [Pineal melatonin exhibits more pronounced antistressor properties than
      anxiolytic diazepam].
AB  - The pineal hormone melatonin (0.1 mg/kg) produced a more pronounced antistressor
      effect as compared to the anxiolytic diazepam (same dose) in rats, which was
      manifested by decreased anxiety, improved heart rhythm variability, and prevented
      stress-induced violation of circadian locomotion. It is suggested that
      differences may result from more expressed hormonal chronotropic activity of
      melatonin.

PMID- 18318188
TI  - [Pharmacological correction of neuronal damage in sensomotor zone of frontal
      cortex under conditions of experimental cerebral blood flow pathology].
AB  - The administration of thiotriazoline, emoxypine and magnelong (a combined glycine
      magnesium preparation) to animals with acute cerebral circulatory insufficiency
      showed significant neuroprotective effect in both acute and late ischemic
      periods, as indicated by the indices of cell density and number and the
      characteristics of apoptic and destructed neurons approaching those in the group
      of intact rats. Pyracetam showed cerebroprotective effect only in late ischemic
      period. Magnelong exhibited the most significant neuroprotective effect,
      maintaining cell density on the intact control level and reducing the number of
      apoptotic and destructed neurons.

PMID- 18318189
TI  - [5-hydroxytryptamine and 5-methoxytryptamine increase tolerance to global
      cerebral ischemia].
AB  - In the global cerebral ischemia, 5-hydroxytryptamine (serotonin, 5-HT) and 5
      methoxytryptamine (5-MT) produce a significant neuroprotector effect closely
      correlated with their hypothermic action. This expands the spectrum of cerebral
      functions controlled by 5-HT. At the same time, melatonin and 2-iodmelatonin,
      which are chemically (but not pharmacologically) close to 5-HT and 5-MT, do not
      exhibit such protective effects. Probably, an important role in the interaction
      with 5-HT receptors belongs to the NH2 group of the indole ring.

PMID- 18318190
TI  - [Anticoagulant activity of low-molecular-weight heparins obtained using a
      hydrolase complex].
AB  - The anticoagulant activity of low-molecular weight heparins (LMWH-PC) with
      average distribution of molecular weights within 3.4-5.8 kD was investigated. The
      samples of LMWH-PC were obtained from unfractionated heparin using immobilized
      enzyme complex of protease C. The LMWH-PC derivatives inhibited the activity of
      blood coagulation factors IIa (thrombin) and Xa. The LMWH-PC derivatives had an
      anti-factor-Xa activity up to 131-208 IU/mg and anti-factor-IIa activity up to 81
      175 IU/mg. All LMWH-PC derivatives form complexes with protamine sulfate during
      electrophoresis in agarose gel. The anticoagulant activity of rabbit plasma
      exhibits a doze-dependent increase upon the intravenous or subcutaneous injection
      of LMWH-PC with a molecular weight of 5.4 kD.

PMID- 18318191
TI  - [Effect of medicinal preparations on the complement: inhibition of subcomponent
      C1q binding to a target].
AB  - A method is developed for determining the inhibition constants of substances
      capable of acting on the complement system at the stage of target recognition
      (immune complexes) by the first component of the complement (and, hence, blocking
      activation of the classical pathway of the complement). The ability of some drugs
      to inhibit the binding of subcomponent C1q to a target has been studied. It is
      shown that some drugs possess a pronounced ability to block the complement
      activation. The inhibition constants are compared to the therapeutic dozes of
      drugs. Some of the investigated preparations (suramin, sodium deoxiribonucleate,
      curcumin, heparin, sulfetron, guttalax, lysozyme) upon administration can present
      in the blood flow in concentrations capable of blocking the complement. The
      method is useful in the search for preparations capable of inhibiting the
      complement and in the study of side effects of medicinal preparations.

PMID- 18318192
TI  - [Effects of sodium humate from peat of Tomsk region on allergic reactions].
AB  - Sodium humate from peat of Tomsk region was tested on three animal models of
      allergic reaction. It was found that sodium humate suppresses the development and
      reduces the intensity of anaphylactic shock in guinea pigs and decreases the
      intensity of the delayed hypersensitivity reaction to goat erythrocytes. It is
      suggested that sodium humate can be a promising substance for the treatment of
      allergic states.

PMID- 18318193
TI  - [Antiinflammatory effect of bischofit ointment].
AB  - A new ointment based on the mineral bischofit exhibits a more pronounced
      antiinflammatory effect on the models of inflammation induced by carrageenin,
      histamine, and serotonin in rats in comparison to the reference ointment
      (vulnuzan). Bischofit ointment stimulates phagocyte activity of neutrophils,
      accelerates the healing and cleaning of infected skin wounds, and produces
      bacteriostatic action.

PMID- 18318194
TI  - [Antiedematous effect of diphenyliodinium salts on experimental toxic lung
      edema].
AB  - A series of diphenyliodinium (DPI) salts (chloride, sulfate, acetate and iodide)
      were synthesized and studied as preventive and therapeutic agents in the model
      toxic lung edema induced by thiourea and phosgene in rats. All DPI salts
      exhibited high antiedematous activity. The preventive action of drugs was more
      effective than their curative effect. The duration of the antiedematous action of
      DPI iodide exceeded 24 h. The effective dose of DPI salts in the toxic lung edema
      was within 0.2-0.5 LD50.

PMID- 18318195
TI  - [Meteoadaptogenic properties of peptide drugs in healthy volunteers].
AB  - The meteoadaptogenic properties of a series of drugs with peptide (cortexin,
      noopept, dilept) and nonpeptide (vinpotropil) structure were investigated in a
      climate thermobarocomplex (Tabay, Japan) on a group of healthy volunteers aged 20
      24. All the studied drugs produced a meteoadaptogenic action, the extent of which
      depended on the environmental test conditions (overcooling, overheating,
      hypobaric hypoxia). Vinpotropil, optimizing a physiological component of the
      functional state, can be recommended as a meteoadaptogen for both cold and hot
      climate as well as for hypobaric hypoxia, where it improved the psychological
      component of the functional state. Cortexin is qualified as an adaptogen and
      actoprotector only for hypobaric hypoxia conditions (uplands). Noopept, affecting
      positively a psychological component of the functional state, can be used for
      rapid adaptation to both cold and hot climate. In the hot climate, noopept also
      enhanced the physical work capacity. Dilept mostly elevated the psychological
      component of the functional state and can be considered as a psychomotor enhancer
      and adaptogen. Therefore, all the drugs studied (vinpotropil, cortexin, noopept
      and dilept) can be recommended as the agents producing activation, support and
      recovery of the physical and psychological efficiency under rapidly changing
      environment conditions.

PMID- 18318196
TI  - [Cardioprotective and antiarrhythmic properties of preparations from Leuzea
      carthamoides, Aralia mandshurica, and Eleutherococcus senticosus].
AB  - It is established that pretreatment with Leuzea carthamoides extract (LCE) (1
      ml/kg per os during 8 days) prevents the development of stress-induced (6-hr
      painful-emotional stress) damage of the rat heart. A chronic administration of
      LCE (1 ml/kg per os during 8 days) increased the cardiac tolerance to the
      cardiotoxic action of D, L-isoproterenol and the arrhythmogenic action of
      epinephrine. Pretreatment with naloxone (2 mg/kg) completely eliminated the
      cardioprotective effect LCE and attenuated but not abolished the antiarrhythmic
      effect of the phytoadaptogen. A chronic administration of LCE elevated the level
      of beta-endorphin levels in the rat blood plasma. It is suggested that the
      cardioprotective effect of LCE is related to an increase in the level of opioid
      peptides, which produce stimulation of the opioid receptors. It is also
      established that preliminary chronic administration of Aralia mandshurica extract
      (AME) increases the cardiac resistance to the arrhythmogenic action of a 45-min
      coronary artery occlusion, but has no effect on the necrosis/risk area ratio. A
      pretreatment with Eleutherococcus senticosus extract (ESE) (1 ml/kg per os during
      8 days) prevented the stress-induced damages of the rat heart. A chronic
      administration of ESE increased the cardiac tolerance to the cardiotoxic action
      of D, L-isoproterenol and the arrhythmogenic action of epinephrine. The
      pretreatment with naloxone (2 mg/kg) completely eliminated both the
      cardioprotective action and the antiarrhythmic effect of the phytoadaptogen. A
      chronic administration of ESE increased the beta-endorphin level in the rat blood
      plasma. It is suggested that the cardioprotective and antiarrhythmic effects of
      ESE is also related to an increase in the endogenous opioid peptide levels. A
      chronic administration of ESE had no effect on the arrhythmogenic effect of a 45
      min coronary artery occlusion and did not change the necrosis/risk area ratio in
      rats.

PMID- 18318197
TI  - [Studying the psychotropic activity of pineal hormone melatonin: original
      direction of our investigations. Twentieth anniversary of the melatonin study in
      the pharmacology department at the Stavropol medical academy].
AB  - Results of a series of original investigations devoted to the antidepressant,
      anxiolytic, and nootropic activity of the pineal hormone melatonin are
      summarized. It is established that a decisive role in this activity belongs to
      the chronotropic properties of melatonin.

PMID- 18318198
TI  - [Glaucoma: cardinal problems, opportunities].

PMID- 18318199
TI  - [The problems of endocrine ophthalmopathy].
AB  - Based on her own rich and many years' experience in following-up and treating
      patients with endocrine ophthalmopathy (EOP) and on the data available in the
      Russian and foreign literature, the author states the problems of EOP. These
      include the terminology and classification of a pathological process, a uniform
      treatment protocol by taking into account its form, compensation and development
      stages, the development of clear indications for decompressive operations on the
      orbit.

PMID- 18318200
TI  - [Evaluation of the efficiency of hydromonitoring phacofragmentation versus
      ultrasound phacoemulsification on the morphometric parameters of the central
      retinal region].
AB  - Morphometric studies using a laser retinal thickness showed great differences in
      the impact of hydromonitoring phacofragmentation and ultrasound
      phacoemulsification on the thickness of the central retinal region. Unlike
      ultrasound phacoemulsification, hydromonitoring phacofragmentation caused no
      transient increase in the thickness of the central retinal area. The performed
      studies revealed no correlation between the equivalent time of ultrasound and
      ultrasound phacoemulsification and the changes in the thickness of the central
      retinal region and fovea.

PMID- 18318201
TI  - [Computed tomographic anatomy of the orbit in the view of a clinician].
AB  - The paper deals with the examination of computed tomograms of 72 patients (90
      orbits), including 29 males (36 orbits) and 43 females (54 orbits), who had no
      any orbital pathology. The patients' age ranged from 34 to 65 years. Data on the
      volume of the bony orbit and its soft tissue contents are given. The dimensions
      of the transversal opening to the orbit and its depth are shown. The volumes of
      all the ocular muscles (extraocular muscles, the elevator muscle of the upper
      eyelid), optic nerve, eyeball, and ocular fat are separately calculated. These
      indices may be used for both the differential diagnosis of true exophthalmos and
      pseudoexophthalmos and the planning of any orbital surgery.

PMID- 18318202
TI  - [Malignant lymphoma of the central nervous system and eye].
AB  - Intraocular lymphoma was encountered in 11.4% of the 79 examined patients with
      malignant lymphoma of the central nervous system. In most cases it had occurred
      long on an average of 26 months before the development of neurological
      manifestations and the diagnosis of cerebral lymphoma. Biomicroscopy showed
      intraocular lymphoma to manifest itself as corneal endothelial precipitation of
      translucent corpuscles, opacity of the vitreous body, and its posterior
      detachment. Isolated intraocular lymphoma has been misinterpreted as uveitis of
      unclear etiology. In this connection, resistance to steroidal and antibacterial
      therapy should be an indication for diagnostic vitrectomy, followed by an
      immunohistochemical study of a biopsy specimen. The intraarterial administration
      of methotrexate, by breaking the blood-brain barrier, caused regression of
      cerebral lymphoma, but did not result in that of intraocular lymphoma, on this
      basis the authors consider the intravitreal injection of the agent to be
      indicated.

PMID- 18318203
TI  - [Clinical value of the local parameters of lipid peroxidation and antioxidative
      defense in patients after cataract extraction].
AB  - The postoperative period of cataract extraction and the parameters of lipid
      peroxidation (LPO) (dienic conjugates, TBA-active compounds) and the
      antioxidative activity (AOA) of tear were studied in 77 patients in relation to
      the type of a surgical intervention--extracapsular cataract extraction (ECCE) and
      phacoemulsification (PE). The incidence of severe postoperative uveitis was more
      than 3 times higher on days both 1 and 5 after surgery. Tear studies revealed a
      significant increase in the concentration of LPO products just on day 1, with its
      further slight increase by day 5 along with a further significant reduction in
      AOA, which indicates the significant consumption of antioxidative defense
      components and the expediency of using antioxidants. Comparison of tear
      biochemical parameters revealed no difference in patients after ECCE and PE.
      Thus, peroxidation processes reflect the severity of an inflammatory reaction in
      the early postoperative period, the study of the processes in tear is a
      noninvasive, high-informative method for recording the balance of LPO and
      antioxidative defense processes, which will assist in determining the direction
      of therapeutic measures to improve the outcome of a surgical intervention.

PMID- 18318204
TI  - [Three-dimensional echography in the diagnosis of hemophthalmia].
AB  - Ultrasound study involving three-dimensional echography was made in 250 patients
      aged 25 to 70 years who had vitreous body hemorrhage of varying etiology. Three
      degrees of acoustic hemophthalmia density: 1) low (from 5 to 25 MG); 2) moderate
      (from 25.1 to 40 MG); 3) high (from 40.1 to 55 MG or higher). According to the
      extent of a pathological focus, the authors identified total hemophthalmia (from
      50 to 100% of the volume of the vitreous body) that is equal to a volume of 2.61
      cm3 or more; disseminated hemophthalmia (from 25 to 50% of the volume of the
      vitreous body) that corresponds to a volume of 1.31 to 2.6 cm3; partial
      hemophthalmia (up to 25% of the volume of the vitreous body) to a volume of 0.1
      to 1.3 cm3. Three-dimensional echography makes it possible to measure the extent
      of intraocular hemorrhage, its acoustic density, to define criteria for
      evaluating the severity of intraocular hemorrhage, and to assess the risk of
      retinal detachment.

PMID- 18318205
TI  - [Role of vascular endothelial growth factor in the development of diabetic
      retinopathy in patients with type 1 diabetes mellitus].
AB  - The influence of vascular endothelial growth factor (VEGF) on the course of
      diabetic retinopathy (DR) was studied in 35 patients, including 11 males and 24
      females, aged 21 to 56 years (mean 37 +/- 2.6 years) who had type 1 diabetes
      mellitus (DM) whose history was 14 to 40 years (mean 21.4 +/- 2.7 years). Tear
      and serum VEGF was examined by solid-phase enzyme-linked immunosorbent assay
      (ELISA), by using diagnostic Bender MedSystems (Austria) on a Stat Fax-2100
      (USA). In the active phase of proliferative DR, the patients with type 1 DM were
      found to have the highest level of tear VEGF; when the process changed to a
      inactive phase, the content of this factor significantly reduced. There was a
      relationship between the tear level of VEGF and the degree of various
      manifestations of DR. There is an agreement of the tear and serum levels of VEGF
      in patients with different stages and manifestations of DR, which may be evidence
      for the single mechanism responsible for vascular endothelial damage in DM. There
      is a relationship between the presence of VEGF, the proliferative stage of DR,
      and diabetic nephropathy.

PMID- 18318206
TI  - [Analysis of the diagnostic efficiency of the Schirmer test versus the lacrimal
      meniscus biometric technique in impaired tear production].
AB  - The paper analyzes the diagnostic capacities of two studies (the routine Schirmer
      test and lacrimal meniscus biometry). It indicates the basic limitations of the
      Schirmer test and describes a procedure for lacrimal meniscus biometry. Based on
      the results of studying the lacrimal meniscus in healthy individuals from a
      control group, the authors revealed a relationship of the height of the lacrimal
      meniscus to the area and horizontal size of the palpebral fissure. Comparison of
      the results of studies of basal lacrimal secretion in the presence of dry
      keratoconjunctivitis and dry eye syndrome in the study patients with
      hypolacrimation defined the latter as mild, moderate, and severe. There was
      discordance between the values in 33.85% of cases. The Schirmer test has not
      shown to be the method of choice in examining basal lacrimal production;
      erroneous results may be obtained in a third of patients. Lacrimal meniscus
      biometry makes it possible to identify the degree of significant hypolacrimation
      more exactly and to minimize the indices of preserved basal secretion.

PMID- 18318207
TI  - [Experience with complex treatment for childhood amblyopia].
AB  - The effects of mexidole on the higher efficiency of treatment for diseases
      involving the visual nerve apparatus and on the achievement of stable visual
      function were studied in children. The study covered a study group of 36 children
      aged 5 to 12 years (mean 8.50 +/- 0.56 years) who had amblyopla of various
      genesis. A control group comprised 30 patients (mean age was 8.20 +/- 0.56 years)
      who had also amblyopia of various genesis and 25 healthy children (mean age was
      8.20 +/- 0.63 years). The patients of the first two groups received the similar
      course pleoptic treatment. Those of the study group were additionally given
      mexidole by the conventional regimen. Mexidole used in children with amblyopia
      enhanced the efficiency of complex pleoptic treatment in 83% of cases and long
      maintained the visual functions achieved during stimulation. The agent has a
      positive effect on the values of visually evoked potentials.

PMID- 18318208
TI  - [Experimental rationale for a transscleral approach to thermotherapy for
      intraocular tumors, by using a photosensitizer].
AB  - The authors present the results of an experimental study of the pattern of
      distribution of laser radiation at a wavelength of 810 nm in the normal and
      Photosens-photosensitized eye tissues and analyze the distribution of a
      temperature at the sclera/choroidea/ tumor border during transscleral radiation
      delivery. To further the goal, the authors have resorted to computer mathematical
      simulation. In convergent-beam radiation supply, the proportion of a scattered
      radiation component has been ascertained to be lower in the surface scleral layer
      than that in the layers adjacent to the choroidea and the base of a tumor. On
      entering the sclera, a splash of light decreases and power density and radiation
      induced heating of the deeply located tissues increase. Thus, the major
      hyperthermic effects show themselves in the tumor rather than on the sclera.

PMID- 18318209
TI  - [Analysis of changes in the accumulation of the photosensitizer Photosens, its
      elimination kinetics and distribution in the tissues of the eye and eyelids in
      health and in some tumorous processes].
AB  - The authors analyze and present the results of spectroscopic studies into changes
      in the accumulation of the photosensitizer Photosens, its elimination kinetics
      and distribution in the tissues of the eye and eyelids, as well as in the tumors
      that have developed at these sites. The findings allowed the authors to estimate
      the duration of the agent's persistence in the eye tissues and the time interval
      associated with the high risk for phototoxic eyelid skin and conjunctival
      reactions and to determine a possibility of and conditions for photodynamic
      therapy, as well as the length of hospital stay when the latter was performed.

PMID- 18318210
TI  - [Pathomorphological changes in the photosensitized eye tissues after transscleral
      laser radiation: experimental studies].
AB  - The authors analyze the pathological changes occurring in the eye tissues after
      their prephotosensitization and transscleral laser radiation at a wavelength of
      810 nm. These changes involve thrombosis of choroidal vessels, destructions of
      retinal photoreceptors and sclerocytes, and rupture of collagenous fibers of the
      deep layers of the sclera with its superficial layers being preserved. These
      changes were recorded just in the direct radiation area. Their magnitude, depth,
      and extent were directly correlated with the power of radiation and the diameter
      of a light splash. In the authors' opinion, the studies performed substantiate a
      transsceral approach for laser radiation in various abnormalities of the
      chorioretinal complex.

PMID- 18318211
TI  - [Wegener's granulomatosis (a case report)].

PMID- 18318212
TI  - [Efficacy a laser ophthalmic destructor used in the treatment of patients with
      eye diseases].

PMID- 18318213
TI  - [Ophthalmic chlamydiasis in young persons: etiology, pathogenesis, clinical
      forms, diagnosis].

PMID- 18318214
TI  - [Ophthalmologic manifestations of Wegener's granulomatosis].

PMID- 18318215
TI  - [Regularities of morphological and functional changes in the retina in its
      detachment and after surgical treatment. Communication 1. Deconstruction and
      restoration of photoreceptors].

PMID- 18318216
TI  - [Regularities of morphological and functional changes in the retina in its
      detachment and after surgical treatment. Communication 2. Remodeling of the
      internal retina].

PMID- 18318217
TI  - [Functional role of proteins containing ankyrin repeats].
AB  - This review describes and discusses new data about the structure and function of
      proteins which contain ankyrin-like repeats in their structure. These proteins
      have been found in cells of different organisms but they are not belonging to the
      cytoskeletal proteins. Many important functions of such proteins are provided by
      ankyrin repeats which maintain protein-protein interactions involved in the
      formation of transcription complexes, initiation of immuno-responses, biogenesis
      and assembly of cation channels in the membranes, regulation of some cell cycle
      stages, symbiotic interactions and many other processes. Mutations in genes
      encoding ankyrin-like proteins can cause defects in gene expression leading to
      diseases onset and progression in animals and humans. Therefore, the structure,
      dynamics and function of these proteins is an area of extensive research in
      modern biology.

PMID- 18318218
TI  - [Effects of antimicrobial peptides of neutrophils on tumor and normal cells in
      culture].
AB  - We performed a comparative study of effects of two structurally different
      cationic antimicrobial peptides of cathelicidin family, porcine protegrin 1 (PG1)
      and caprine bactenecin 5 (Bac5) on selected tumor and normal mammalian cells in
      vitro. Protegrins are amphiphilic beta-hairpin molecules having broad-spectrum
      antimicrobial activity due to their marked membranolytic properties. Bac5 belongs
      to the group of proline-rich peptides, which adopt a polyproline type II extended
      helix and kill microorganisms rather by a non-lytic mechanism. We have shown that
      while PG1 exerts distinct and fast cytotoxic effects on most of used tumor cells
      being slightly less toxic for nontransformed host cell, the proline-rich Bac5 is
      much less cytotoxic for all the cells tested. The toxic effects of PG1 were
      partially declined in the presence of 10% fetal calf serum. It was revealed that
      PG1 was able to interact with proteins of serpin family (as had been previously
      established for human defensins by Panyutich et al., 1995). Pre-incubation of PG1
      with alpha1-antitrypsin caused the decrease of the cytotoxic activity of the
      peptide and, on the other hand, the antiprotease activity of alpha1-antitrypsin
      was reduced after interaction of the serpin with PG1 (not with Bac5). Confocal
      microscopy experiments allowed to monitor the internalization of fluorescent
      labeled (by BODIPY FL) peptides into target cells and their intracellular
      distribution. Bac5-BODIPY (at 5 microM) was rapidly taken into the cells. PG1
      BODIPY at non-toxic concentrations was also able to enter the cells without
      significant damage to them. The comparative study of the kinetics of the peptides
      uptake into the target cells and the influence of low temperature, energy
      depletion and endocytosis inhibitors on the process of the internalization of the
      peptides into the cells was carried out using flow cytometry.

PMID- 18318219
TI  - [Microfluorimetric analysis of dynamics of genomic changes of Chinese hamster
      fibroblasts CHL V-79 RJK with multidrug resistance].
AB  - Results of karyological analysis of cells CHL V-79 RJK selected for resistance to
      ethidium bromide (EB) causing multidrug resistance (MDR) (line Vebr-5) were
      compared with the data of microfluorimetric determination of DNA content in
      individual chromosomes of the karyotype. The analysis was performed at the 11th
      and 88th passages. Karyotyping of Vebr-5 has shown the presence of an additional
      genetic material (ADM) in the form of homogenously or differentially stained
      regions (HSRs and DSRs, respectively) in two chromosomes (Z1 and Z6, loci 1 p29
      31 and 1q26, respectively). HSRs in Z6, in the region of localization of the wild
      type of gene mdr, had unstable length and structure characteristic of
      morphological markers of amplification of genes of the family mdr. During long
      cultivation of Vebr-5 in the presence of EB (88 passages), the instability of
      HSRs in Z6 increased. Results of microfluorimetric analysis of Vebr-5 at the 11th
      passage have shown an increase in the DNA content not only in chromosomes Z1 and
      Z6 marked by HSRs, but also in three chromosomes (Z5, Z12 and Z13) that have no
      visual morphological changes. The corresponding analysis at the 88th passage has
      also revealed non-random changes in the DNA content in four more chromosomes: an
      increase in Z14, while a decrease in chromosomes 8, Z7, and Z9. A decrease of the
      DNA content in chromosomes is considered to be a result of a partial loss of
      genetic material, while its increase is a result of its translocation and (or)
      amplification. Coefficient of variation of the DNA content changes for large
      chromosomes amounted to about 9%. while for small chromosomes it is about 26%,
      which indicates that small chromosomes have greater potential for instability
      than the large ones. The data obtained not only confirm, but also enlarge the
      concept of directions and character of destabilization of the cell genetic
      apparatus in the process of neoplastic transformation due to the MDR acquisition
      by cells.

PMID- 18318220
TI  - [E-cadherin affects MAP activation by growth factors stimulation in human
      carcinoma cells].
AB  - Met and EGF receptor (EGFR) activation is correlated with dissociation of cell
      cell adhesion and with increase in mobility of cancer cells. E-cadherin is a
      major protein of adhesion junctions. Using different approaches we have shown
      that EGF receptors intracellular localization depends of E-cadherin function. It
      was found that EGFR localized on the membrane in HT-29 cells which formed mature
      cell-cell contacts. Moreover, EGFR was colocalized with E-cadherin at the site of
      cell-cell adhesion in Triton-insoluble fraction. EGFR was accumulated preliminary
      in cytosol in E-cadherin negative HBL-100 cells. Study of signal transduction
      mediated by EGF and HGF in cells with different state of cell adhesion
      demonstrated that E-cadherin could affect ERK-signal-duration. Our preliminary
      studies proposed that mislocalization of Met and EGFR in E-cadherin negative
      cells altered receptors downstream signaling.

PMID- 18318221
TI  - [Studies of interaction of intracellular signalling and metabolic pathways under
      inhibition of mitochondrial aconitase with fluoroacetate].
AB  - Mitochondrial aconitase has been shown to be inactivated by a spectrum of
      substances or critical states. Fluoroacetate (FA) is the most known toxic agent
      inhibiting aconitase. The biochemistry of toxic action of FA is rather well
      understood, though no effective therapy has been proposed for the past six
      decades. In order to reveal novel approaches for possible antidotes to be
      developed, experiments were performed with rat liver mitochondria, Ehrlich ascite
      tumor cells and cardiomyocytes, exposed to FA or fluorocitrate in vitro. The
      effect of FA developed at much higher concentrations in comparison with
      fluorocitrate and was dependent upon respiratory substrates in experiments with
      mitochondria: with pyruvate, FA induced a slow oxidation and/or leak of pyridine
      nucleotides and inhibition of respiration. Oxidation of pyridine nucleotides was
      prevented by incubation of mitochondria with cyclosporin A. Studies of the
      pyridine nucleotides level and calcium response generated in Ehrlich ascite tumor
      cells under activation with ATP also revealed a loss of pyridine nucleotides from
      mitochondria resulting in a shift in the balance of mitochondrial and cytosolic
      NAD(P)H under exposure to FA. An increase of cytosolic [Ca2+] was observed in the
      cell lines exposed to FA and is explained by activation of plasma membrane
      calcium channels; this mechanism, could have an impact on amplitude and rate of
      Ca2+ waves in cardiomyocytes. Highlighting the reciprocal relationship between
      intracellular pyridine nucleotides and calcium balance, we discuss metabolic
      pathway modulation in the context of probable development of an effective therapy
      for FA poisoning and other inhibitors of aconitase.

PMID- 18318222
TI  - [Comparative analysis of Ca(2+)-signalling in brown preadipocytes of ground
      squirrel Spermophillus undulatus and mouse].
AB  - Analysis of the slow Ca(2+)-responses of brown preadipocytes of ground squirrel
      Spermophillus undulatus and mouse was carried out. The mouse brown preadipocytes
      demonstrated low but prominent responses to noradrenalin with the maximum at 3
      and 10 microM being the less effective. The ground squirrel brown preadipocytes
      practically did not practically respond to 10 nM-10 microM, whereas 30-600 microM
      noradrenalin was able to raise intracellular [Ca2+]i up to 600 nM with 300 microM
      agonist being the most effective. Stimulation of the plasma membrane Ca(2+)
      channels with thimerosal showed considerable reduction of the calcium entry
      system in the cell precursors of both species comparing with their mature
      adipocytes. Intracellular calcium stores liberated in preadipocytes of both
      species by tapsigargin and ionomycin in Ca(2+)-free medium were insignificant,
      and capacitative Ca(2+)-entry in response to the cellular Ca(2+)-stores depletion
      was completely absent in Ca(2+)-containing medium. The Ca(2+)-responses of the
      ground squirrel brown preadipocytes were independent on physiological state of
      the animals and annual seasons. Preadipocytes of both species showed the same
      dose-response curves for the Ca(2+)-raise under thimerosal, and the mouse had two
      fold higher kinetic constants for the Ca2+ ions entry. The ground squirrel brown
      adipocytes responded to ionomycin with approximately 25% higher increase in
      [Ca2+]i and the entry of the ions had 7-10-fold higher kinetic constants for this
      process. Kinetic constants for the [Ca2+]i raise in mouse preadipocytes were
      independent of ionomycin concentration, whereas in the ground squirrel brown
      preadipocytes the constant linearly increased with the ionophore concentration.
      It is suggested that the found difference in the function of Ca(2+)-signalling in
      preadipocytes of two species, which becomes apparent in the presence of
      ionomycin, might be responsible for the observed difference in the noradrenalin
      induced cellular Ca(2+)-responses as well.

PMID- 18318223
TI  - [Comparative analysis of tuberculosis morbidity in children and adolescents from
      Moscow and the Penza Region].
AB  - Tuberculosis morbidity was comparatively analyzed in the children and adolescents
      of Moscow and the Penza Region. The epidemiology of tuberculosis in the children
      and adolescents was established to be universal in the compared regions in the
      study period. This manifested itself as a stable tendency for higher morbidity
      rates (MR), increased incidence of destructive tuberculosis, inadequate use of
      the existing methods for active detection of tuberculosis in these age groups,
      and, among those who had fallen ill with this disease, an increase in the number
      of persons from the foci of tuberculous infection and persons with established
      contact with patients with tuberculosis. Along with a steady MR growth for
      tuberculosis among the children and adolescents, there has been a quantitative
      modification to the proportion of all epidemiologically hazardous forms of
      tuberculosis, such as the bacillary and destructive forms of pulmonary
      tuberculosis complicated by extrapulmonary tuberculosis. Hypodiagnosis of
      tuberculous pleurisy and extrapulmonary tuberculosis has been recently noted in
      the general health care network. The analysis also leads to the conclusion that
      the quality of mass tuberculin diagnosis remains poor. In both regions, general
      pediatricians are not adequately alert to tuberculosis, extrapulmonary
      tuberculosis in particular. With a rise in tuberculosis endemic, the incidence of
      tuberculosis in 18-21-year-old persons is 2-3 times greater than that in
      adolescents, which is associated with the greater activity of this population
      group and with the underdetection of the asymptomatic forms of tuberculosis in
      adolescents.

PMID- 18318224
TI  - [A systemic inflammatory response in teenagers with new-onset tuberculosis].
AB  - Fifty-eight adolescents aged 13-17 years who had new-onset pulmonary tuberculosis
      were examined. The serum levels of C-reactive protein (CRP), alpha-antitrypsin
      (alpha1-AT), haptoglobin (Hp), serum protein fractions, medium-weight molecules
      (MWM), and malonic dialdehyde (MDA) were assayed in the patients on admission, 2
      weeks, and 1, 2, 3, and 6 months after treatment. The parameters of a systemic
      inflammatory response were ascertained to naturally vary in the adolescents with
      new-onset tuberculosis, by reflecting as both a defense reaction (increases in
      the levels of CRP, a,-AT, Hp) and as metabolic decompensation manifestations
      (increases in the concentrations of MWM and MDA and a reduction in the
      almubin/globulin (A/G) ratio. The magnitude of these changes makes it possible to
      judge the severity of a process to a certain extent and it is unassociated with
      the genesis of the disease. The levels of acute-phase reagents and MDA undergo
      positive changes just 2 weeks of effective specific chemotherapy whereas there
      are no changes after ineffective treatment. After correction of chemotherapy and
      achieving a clinical effect, there was a complete normalization in the levels of
      CRP, Hp, and A/G ratio, but a slight increase in alpha1-AT and MDA in all the
      children by month 6 of therapy. In all the adolescents, the baseline increased
      concentration of MWM increased at the early stage of chemotherapy and returned to
      the original value after 6-month therapy, by remaining significantly higher than
      the normal values.

PMID- 18318225
TI  - [Adenosine deaminase in the blood cells and serum of patients with tuberculous
      pleurisy].
AB  - The common complication of pulmonary tuberculosis is pleurisy that requires not
      only special treatments, but also gives rise to difficulties in the differential
      diagnosis of tuberculosis. The investigation has studied the possibility of
      determining the activity of adenosine deaminase (ADA) as a marker of pleural
      effusion of tuberculous etiology. The patients with tuberculous pleurisy have
      been found to have higher lymphocytic and red blood ADA, and ADA, activities and
      a significantly increased serum ADA2 activity. Thus, the changes in the activity
      of ADA and its isozymes have been shown to be specific to pleurisy of tuberculous
      etiology and to be of diagnostic value.

PMID- 18318226
TI  - [The specific features of new-onset tuberculosis in medical workers of the
      Krasnoyarsk Territory].
AB  - The occupational pattern and clinical characteristics of 587 medical workers
      detected as having tuberculosis over 13 years in the Krasnoyarsk Territory are
      analyzed. The distinctive features of the pattern of clinical forms of a
      tuberculous process and its characteristics have been identified in the medical
      workers as compared with nonmedical workers and regional differences have been
      also revealed. The reasons are shown for higher tuberculosis morbidity in
      physicians. There is evidence for the leading role of exogenous superinfection
      and its nosocomial pattern in the development of tuberculosis in medical workers.
      Pitfalls associated with the fact that the administrators of therapeutic-and
      prophylactic and medical facilities exercise lax control over regular
      fluorographic studies of medical workers have been established in the
      organization of active tuberculosis detection. The findings are as a basis for
      developing a new guideline for the detection and prevention of tuberculosis in
      medical workers under the established epidemic situation.

PMID- 18318227
TI  - [Infiltrative pulmonary tuberculosis in persons over 60 years of age].
AB  - To study the specific features of infiltrative pulmonary tuberculosis and its
      treatment efficiency in patients over 60 years, the authors analyzed case
      histories of 80 patients who were divided into 2 groups: 1) 40 patients aged 60
      years or more and 2) 40 patients aged 18 to 50 years. The types of adaptive
      reactions (L. Kh. Garkavi et al., 1977) and those of the body's responsiveness
      (N. A. Brazhenko, 1987) were studied; the leukocytic shift index (N. I.
      Yabluchansky, et al., 1983) was calculated. The efficiency of treatment was
      evaluated from the results of control bacteriological and X-ray studies conducted
      after 2-, 5-, and 8-month drug therapy. The persons over 60 years of age were
      significantly more frequently (p < 0.05) diagnosed as having concomitant diseases
      (mainly coronary heart disease (65%), arterial hypertension (50%), chronic
      bronchitis (50%), atherosclerosis of central and peripheral arteries (35%), and
      adverse reactions caused by antituberculous drugs (75% versus 40%; among them
      there were prevalent neurotoxic and cardiotoxic reactions). Despite the fact that
      the results of treatment in this group of patients did not differ from those in
      young persons, which may be attributable to better compliance in patients above
      60 years of age.

PMID- 18318228
TI  - [Results of treatment in patients with destructive pulmonary tuberculosis without
      consideration of drug sensitivity in Mycobacterium tuberculosis].
AB  - Treatment of 63 patients having infiltrative and disseminated pulmonary
      tuberculosis attended by decay and bacterial excretion with 4 essential drugs
      (isoniazid, rifadine, pyrazinamide, ethambutol) and, in disseminated processes,
      additionally with streptomycin without determining their drug sensitivity
      contributed to the cessation of sputum acid-resistant mycobacteria in 96.8% and
      to cavity cicatrisation in 77.8%. Irregular use of izoniazid and rifadine during
      continued treatment is one of the reasons for the low rates of cavity resolution.

PMID- 18318229
TI  - [A case of development of acute miliary tuberculosis].

PMID- 18318230
TI  - [Precautions regarding prevent acute urethritis caused by Neisseria meningitidis
      in Japan].
AB  - In Japan, Neisseria meningitidis is not sufficiently recognized as the primary
      causative bacteria of sexually transmitted diseases (STDs) as the number of
      reported cases is small. Here, we summarize reports from 3 medical institutions,
      present clinical courses for each case, as well recommending precautions to
      prevent infection with this bacterium. Fourteen cases of N. meningitidis
      urethritis (MU) were admitted between April 2001 and June 2006. All patients were
      male, consulted a doctor after experiencing subjective symptoms, such as
      micturition pain and pus discharge, and were diagnosed as having urethritis using
      isolation culture methods. In 8 of the 14 cases, history of sexual contact in the
      preclinical stage was confirmed, and contact was with a commercial sex worker
      (CSW) in 6 of these cases. Many of these patients recalled oral contact. All
      strains indicated susceptibility to many drugs, and there were no problems with
      treatment. With regard to serotype, there were 10 cases of type Y, 1 case of type
      B, and 3 cases that were not classifiable or unidentified. In addition, among the
      9 strains that were subjected to genotype identification, 7 strains were ST-23.
      The recent increase in availability of nucleic acid amplification methods has
      facilitated simultaneous detection of Neisseria gonorrhoeae and Chlamydia
      trachomatis. However, we fear that MU will become latent. For screening of
      urethritis, Gram staining and culture of urethral material must be performed to
      detect this disease. The relationship of the detected strain and its role in the
      pathogenesis of meningitis are uncertain, but its serotype and genotype are
      common in cases of meningitis. Thus, precautions are required to prevent spread
      of this bacterium.

PMID- 18318231
TI  - [Pathophysiology and laboratory findings in measles].
AB  - Measles is a highly contagious disease characterized by a prodromal illness of
      fever, coryza, cough, and conjunctivitis followed by the appearance of a
      generalized maculopapular rash. Despite the availability of an effective and safe
      live attenuated vaccine, measles remains a cause of continuing outbreaks in
      Japan. Measles often accompanies diverse complications, including pneumonitis,
      otitis media, and central nervous system involvement. Neurological complications
      of measles includes ADEM, MIBE, and SSPE. MIBE and SSPE have unfavorable
      prognosis, which are caused by persistent infection of particular mutants of
      measles virus (MV) in brain. In SSPE patients, measles antibody titer increase in
      cerebrospinal fluid and serum. Primary vaccine failure and secondary vaccine
      failure may be a major cause of outbreaks in Japan, therefore, promotion of
      vaccination should be emphasized. 2 doses vaccination methods began in Japan in
      2006, and supplementary vaccination program at 12 and 18 years old begins from
      2008. Protection level of antibody titer varies according to the antibody
      measurement methods. NT provides the best correlate for protection from
      infection, however, needs complicated procedure. PA is chosen for the
      surveillance method in Japan, and 1:128 or over seems protection level. To
      protect health-care associated infection of MV, all health care worker under 35
      years old should be vaccinated if not have adequate immunity.

PMID- 18318232
TI  - [How to produce research information from the clinical laboratory--review of our
      research on the cytological diagnosis of aspergillosis].
AB  - We have evaluated the significance of the cytopathological diagnosis of pulmonary
      aspergillosis using touch smears or lavage fluid obtained by the bronchoscopic
      examination. Thirty five cases of aspergillosis were diagnosed through the
      cytological examination of bronchoscopic specimens with abundant neutrophils or
      necrotic debris from 211 patients. Thirty three of these 35 cases were non
      invasive or semi-invasive and the remaining two cases were allergic
      aspergillosis. Aspergilli could be cultivated from the bronchoscopic specimen
      only in 34% of these 35 cases. Serum beta-D glucan and galactomannan were
      elevated in 27% and 12% respectively. Although 92% of these 35 cases had high
      titer of aspergillus antibody, less than 40% of them had been suspected to be
      aspergillosis at the time of bronchoscopic examinations. These data clearly
      indicates that cytopathological examination is quite effective to make the
      diagnosis of pulmonary aspergillosis especially in the clinically unsuspected
      cases. Our experimental study revealed that Papanicolou's staining is able to
      color the cytoplasm of the fungal hyphae but ineffective to demonstrate empty
      wall of the degenerated hyphae. In our 35 aspergillosis, hyphae are frequently
      invisible in the slides stained with Papanicolou's method (21/35), because of the
      degenerative change. However, degenerated hyphae of these 21 cases were clearly
      demonstrated by special stain for fungi. In conclusion, application of the fungal
      stain to the bronchial cytological slides rich in neutrophils and/or necrotic
      debris is revealed to have clinical significance for the accurate diagnosis of
      pulmonary aspergillosis.

PMID- 18318233
TI  - [Hope for the clinical laboratory: from the viewpoint of the thyroidologist].
AB  - We have tried to screen for hyperthyroidism by neural networks using routine test
      data (without hormonal data), and found that screening with a set of three
      parameters (alkaline phosphatase, creatinine, and total cholesterol) allowed for
      quite accurate screening. The trouble in this study was that the methods of
      measurement for blood chemistry have sometimes changed in our hospital and the
      reference ranges have changed accordingly. Therefore, the data obtained several
      years ago could not be used. There were also remarkable inter-laboratory
      differences in free thyroxine measurement. We hope that the standardization of
      clinical laboratory measurement will be achieved in nationwide in the near
      future.

PMID- 18318234
TI  - [Development of measurement methods and contributions to medical care in the
      clinical laboratory].
AB  - The level of professional interest in clinical chemistry shown by technologists
      tends to erode as the recent advances in automation of clinical laboratory tests
      have made it possible to obtain accurate data by simply using reagent kits.
      Therefore, the most of medical technologists have foolish preconceptions to be
      impossible for the development of the new measurement methods in the clinical
      laboratory. However, there should be many studies that medical technologist
      should perform. In this paper, I give an outline about practice of the chemical
      reagent development in the laboratory and the effect mainly on the HDL
      cholesterol (HDL-C) homogeneous method which we developed. Because homogenous
      methods can easily be performed by automated analyzers, they have been widely
      implemented not only in Japan, but also throughout the rest of the world. When
      compared to the precipitation methods requiring centrifugation, homogenous assays
      are superior because of the great savings in manpower, many more samples can be
      analyzed within a given time, smaller quantities of samples are required, assay
      times are shorter, and measurement accuracy is greater. The most important
      contribution of homogenous assays is that because measurement accuracy is higher,
      the degree of inter-laboratory differences has been markedly decreased, thus
      making it possible to establish international standards.

PMID- 18318235
TI  - [Development, manufacture and sales of products for diagnosis of disease].
AB  - Final version of "Chronic kidney disease (CKD) Practice Guide" book is displayed
      on the Japanese Society of Nephrology (JSN) homepage in April, 2007. JSN
      epidemiology working-group finally approved the glomerular filtration rate (GFR)
      estimation equation for Japanese. Serum creatinine (Cr) should be measured by
      enzyme method. The modified the abbreviated MDRD Study equation for Japanese is
      already printed in the "CKD practice guide". GFR = 175 x Cr(-1.154) x Age (
      0.203) x 0.741 (if women 0.742) The limit of detection of enzymatic method of
      serum creatinine is at least 0.02 mg/dL to evaluate GFR accurately. Moreover,
      Japanese Government will assume decreasing the number of the prevalence and
      reserve of the lifestyle related disease up to present 25% to be a policy
      objective by 2015. And, it obligated the checkup and the health guidance
      specially provided to the employee of 40 years or more who worked in each
      corporation to be executed on April 1, 2008. The spread of the automatic clinical
      analyzer reduces a necessary amount of the specimen and the amount of the
      reagent, and has reduced time and the cost of clinical chemistry test greatly.
      The environment of the clinical examination will change in the future, and useful
      information for the patient and the doctor change again like this. To offer
      information suitable for needs in the changing age, the researcher who works at
      the site of the clinical examination and the researcher who works at the site of
      the reagent development should cooperate mutually, and continue study and the
      effort.

PMID- 18318236
TI  - [Topics in renal physiology: transgenic animals and cellular signaling].

PMID- 18318237
TI  - [Progress in nephrology during this year: Basic research for kidney diseases].

PMID- 18318238
TI  - [Progress in nephrology during this year: Clinical nephrology].

PMID- 18318239
TI  - [Progress in nephrology during this year: Kidney and hypertension].

PMID- 18318240
TI  - [Progress in nephrology during this year: Water electrolyte metabolism].

PMID- 18318241
TI  - [Progress in nephrology during this year: Renal transplantation].

PMID- 18318242
TI  - [Guidelines for the treatment of childhood IgA nephropathy].

PMID- 18318243
TI  - [Validation of the Japanese SF-36 v2 acute form in patients with chronic kidney
      disease].
AB  - OBJECTIVE: The SF-36v2 (version 2 of the SF-36 health survey) is an instrument
      used worldwide to measure the generic health-related quality of life (HQOL). The
      SF-36v2 has "standard" and "acute" forms, in which respondents are asked about
      the previous month and the previous week, respectively. The standard form of the
      Japanese-language version of the SF-36v2 has already been validated, but the
      acute form has not. We evaluated the validity and reliability of the Japanese SF
      36v2 acute form in patients with chronic kidney disease (CKD). METHODS: Cross
      sectional data from 210 CKD patients who enrolled a clinical trial of a long
      acting erythropoiesis stimulating agent (darbepoetin alfa) were analyzed. The
      feasibility of question items and distributions of the response choices were
      examined. Cronbach's alpha was computed to assess internal-consistency
      reliability. Construct validity was evaluated with tests of convergent and
      discriminant validity, and with factor analysis. Validity with regard to
      reference groups for the severity of anemia and for performance states was also
      assessed. RESULTS: There were few missing data and the distribution of response
      choices did not differ between the acute form and the standard form. Values of
      Cronbach's alpha for the acute form sub-scales were sufficient. The percentages
      of items that passed the tests of convergent validity and discriminant validity
      were 100% and 98.7%, respectively. Factor analysis identified the same components
      in the acute form as in the standard form. "Dose-response" relationships were
      found between the sub-scale scores on the acute form and the severity of anemia,
      and also between those scores and performance states. CONCLUSIONS: The Japanese
      SF-36v2 acute form can be expected to provide valid and reliable HQOL data in CKD
      patients.

PMID- 18318244
TI  - [Crescentic and necrotizing glomerulonephritis with C3 deposition].
AB  - Case 1: A 38-year-old female with a history of tonsillitis and sinusitis was
      admitted to our hospital because of lung edema. On admission, her serum
      creatinine increased to 5.57 mg/dL. Hypocomplementemia was not found. ASO and MPO
      ANCA were 24 U/mL and 12 EU, respectively. She underwent emergency hemodialysis.
      Renal biopsy showed global sclerosis and fibrocellular crescentic formation, and
      marked angionecrosis was noted by light microscopy. Granular deposition of C3,
      IgG and IgM was seen along the capillary walls on immunofluorescence study.
      Glomerular intramembranous deposits were scattered on electron microscopy. She
      was treated with intravenous methylprednisolone pulse therapy, and following oral
      prednisolone administration was decreased gradually. No therapeutic effects were
      observed, and intermittent hemodialysis was continued and became maintenance
      hemodialysis therapy. Case 2: A 28-year-old female suffering from both
      pharyngitis and acute renal failure with systemic edema was admitted to our
      hospital. On admission, her serum creatinine and ASO were 4.31 mg/dL and 239
      U/mL, respectively. MPO-ANCA was negative and CH50 was normal. Hemodialysis was
      initiated on the 6th hospital day. In renal biopsy, most glomeruli showed
      cellular crescentic formation, and marked angionecrosis was noted by light
      microscopy. Global sclerosis was not found in this case. Granular deposition of
      C3 resembling a starry sky pattern was seen along the capillary walls on
      immunofluorescence study. Electron microscopy revealed scattered glomerular
      subepithelial deposits. She was treated with intravenous methylprednisolone pulse
      therapy and then oral prednisolone administration. Because of the gradual
      improvement in renal function, hemodialysis was terminated after 53 sessions,
      however, the patient's chronic renal failure has persisted to date. In these two
      cases, the pathological findings supported the diagnosis of severe acute post
      infectious glomerulonephritis with the characteristic crescentic and necrotizing
      glomerulonephritis with C3 deposition.

PMID- 18318245
TI  - [Rhabdomyolysis in a patient with postoperative hypothyroidism and
      hypoparathyroidism].
AB  - The patient was an 81-year-old woman with postoperative hypothyroidism and
      hypoparathyroidism who developed rhabdomyolysis and acute renal failure. She had
      been on levothyroxine and vitamin D replacement therapy for 35 years following
      removal of the thyroid and parathyroid for Grave's disease, although her drug
      compliance had been poor for 6 months prior to admission due to senile dementia.
      She presented with anorexia, general malaise and gait disturbance. Rhabdomyolysis
      was diagnosed by elevated CK and serum myoglobin, and the difference between
      urinary blood occult reaction and red blood cell count. BUN and serum creatinine
      levels were 44.3 mg/dL and 1.9 mg/dL, respectively. The patient was immediately
      administered intravenous fluid and was started on levothyroxine and alfacalcidol
      replacement therapy, which improved the symptoms and laboratory findings. To the
      author's knowledge, this is the first case of rhabdomyolysis caused by both
      hypothyroidism and hypoparathyroidism.

PMID- 18318246
TI  - [Case of scleroderma with rapid progressive glomerulonephritis associated with
      both MPO-ANCA and anti-GBM antibodies].
AB  - A 66-year-old male with scleroderma developed rapidly progressive
      glomerulonephritis (RPGN). Renal pathology revealed crescentic glomerulonephritis
      with interstitial inflammation and fibrosis. Immunofluorescent micrography showed
      linear deposition of IgG along the glomerular capillary wall. Both anti
      glomerular basement membrane antibody (anti-GBM Ab), and myeloperoxidase
      antineutrophil cytoplasmic antibody (MPO-ANCA) were detected by an enzyme-linked
      immunosorbent assay (ELISA). These findings were compatible with ANCA-related
      vasculitis and anti-GBM Ab nephritis. Laboratory findings showed rapid elevation
      of the serum creatinine level (5.9 mg/dL), and a high titer of MPO-ANCA (530 EU)
      and anti-GBM Ab (21 EU). He was started on methylprednisolone pulse therapy and
      temporary hemodialysis. Since the immunosuppressive therapy lowered both antibody
      titers steadily and improved renal function, hemodialysis was discontinued 4
      weeks after the therapy. It has been reported that some scleroderma patients
      developed rapid progressive glomerulonephritis due to ANCA-associated vasculitis
      in addition to the typical scleroderma renal crisis. There have been few reports
      of a scleroderma patient associated with RPGN, in whom both MPO-ANCA and anti GBM
      antibodies were detected.

PMID- 18318247
TI  - [Macroscopic subtypes of asbestosis in relation to the amount of asbestos in 63
      Japanese autopsy cases].
AB  - Atelectatic induration (AI) and honeycombing (HNCB) are two distinct macroscopic
      features of asbestosis. The current study was undertaken to clarify whether or
      not there might be a relation between the macroscopic type of asbestosis and
      burden of asbestos fibers in the lung. The material (N = 63) derived from 58
      autopsies and 5 surgically removed lungs with lung cancers, which comprised 22
      cases of AI (mean age: 67 years: 20 males and 2 females) and 41 cases of HNCB
      (mean age: 66 years: 38 men and 3 women) types of asbestosis, respectively. The
      quantification of asbestos bodies (AB) and fibers (AF) was carried out using
      Kohyama's method. The AI type showed 260,000 +/- 460,000 AB per 1g of wet lung
      and 920,000 +/- 1,360,000 AF per 1g of dry lung, whereas HNCB showed 44,000 +/-
      93,000 AB and 200,000 +/- 490,000 AF, respectively. These differences were
      statistically significant between the types of asbestosis (p < 0.01). Diffuse
      pleural thickening and upper lobe involvement were more advanced in the AI type
      and the differences were statistically significant between subtypes (p < 0.05).
      In conclusion, asbestos load is considered to be a factor related to the
      macroscopic subtype of asbestosis.

PMID- 18318248
TI  - [Clinical and pathological analysis of 10 cases of secondary pneumothorax due to
      angiosarcoma of the scalp].
AB  - Angiosarcoma of the scalp is a very rare disease. Secondary pneumothorax is known
      as a characteristic complication in this disease due to lung metastasis. In this
      study, 17 patients of angiosarcoma of the scalp, diagnosed at our hospital
      between 1996 and 2006, were analyzed. Secondary pneumothorax was observed in 10
      of these patients, among which bilateral pneumothorax occurred in 5 relapse of
      pneumothorax occurred in 6 and pneumothorax with bloody pleural fluid occurred in
      7 patients. Characteristic findings on chest CT were multiple thin-wall cavities
      and ground-glass attenuation around the cavity, located in bilateral subpleural
      lung fields. It is suggested that the subpleural thin-wall cavities cause
      pneumothorax. Although pleurosclerosis were performed in 5 patients and one of
      them had a subsequent partial resection of the lung, pneumothorax reocurred
      within a short period of time in all patients. The average survival time from the
      first pneumothorax episode was only 4.1 months. Secondary pneumothorax caused by
      this disease was intractable, resulting in an unfavorable outcome. It is
      necessary to develop a proper treatment strategy for secondary pneumothorax to
      create a favorable prognosis in this disease.

PMID- 18318249
TI  - [Clinical effects of intravenous ciprofloxacin on community-acquired pneumonia
      with positive Immunocard Mycoplasma test results].
AB  - We studied the clinical effects of intravenous ciprofloxacin (CPFX) on community
      acquired pneumonia in patients with positive Immunocard Mycoplasma test results.
      The subjects were 35 patients (59.4 +/- 24.8 years old) with community-acquired
      pneumonia with positive Immunocard Mycoplasma test results. We infused CPFX 300mg
      copy intravenously twice daily for 3-14 days. It was effective in 33 of 35
      patients, with an efficacy rate of 94.3%. Adverse reactions consisted of itching
      in 2 patients, malaise in 2 patients, drug eruption in 1 patient, elevation of
      GPT in 1 patient and elevation of BUN in 1 patient, but all were mild. We
      conclude that intravenous CPFX is useful for community-acquired pneumonia in case
      with positive Immunocard Mycoplasma test results.

PMID- 18318250
TI  - [Case of HLA-DR8 positive sarcoidosis following polymyositis and Sjogren's
      syndrome].
AB  - A 69-year-old woman had been found to have idiopathic interstitial pneumonia
      (fibrotic NSIP) in 1997. Proximal muscle weakness appeared in April 2005. Chest
      CT revealed hilar and mediastinal lymphadenopathy. Polymyositis and Sjogren's
      syndrome were subsequently diagnosed. We assumed that the interstitial pneumonia
      had preceded polymyositis and Sjogren's syndrome. A muscle biopsy and
      transbronchial needle aspiration biopsy demonstrated noncaseating epithelioid
      cell granulomas. A diagnosis of sarcoidosis complicated with polymyositis and
      Sjogren's syndrome was made from these findings. Moreover, her HLA genotype
      contained DR8. HLA-DR8 is considered to be associated with polymyositis,
      Sjogren's syndrome, and sarcoidosis in Japanese patients. This case suggests the
      possibility that there are common immunological and genetical pathogenetic
      mechanisms in autoimmune diseases and sarcoidosis.

PMID- 18318251
TI  - [Case of agranulocytosis associated with thymoma].
AB  - A 75-year-old-woman had undergone extended thymectomy, right upper and middle
      lobe resection, and radiation therapy (40 Gy) for thymoma at the age of 63. She
      visited our hospital complaining of low grade fever, cough, anorexia and a sore
      throat. Peripheral blood count revealed agranulocytosis. Agranulocytosis
      associated with thymoma was diagnosed, because there were no other possible
      causes of agranulocytosis such as drugs, infection, recent radiation therapy, or
      bone marrow invasion. In spite of giving G-CSF, steroid therapy and
      immunosuppressants, she died of pneumonia caused by agranulocytosis. We consider
      that agranulocytosis is a very rare complication of thymoma.

PMID- 18318252
TI  - [Case of idiopathic bronchiolitis obliterans successfully treated by medication].
AB  - A 53-year-old woman visited a clinic for stridor and dyspnea, and was treated
      with steroid and heparin for bronchial asthma and pulmonary embolism. She was
      later admitted to our hospital for progressive dyspnea. Blood gas analysis showed
      severe hypoxemia with hypercapnia. Pulmonary funtion tests revealed severe
      obstractive pulmonary dysfunction. Chest computed tomography showed a mosaic
      perfusion pattern. Ventilation-perfusion scanning showed bilateral multiple
      matched defects, especially in the basal region. Since specimens of Video
      assisted thoracoscopic surgical (VATS) lung biopsy showed lymphocytic
      infiltration in membranous bronchiole and occlusion of the membranous bronchiole
      lumen, bronchiolitis obliterans was diagnosed. We initiated treatment with
      steroids, macrolides and bronchodilators and her condition stabilized. Although
      these therapies did not cure the BO, they did retard its progression.

PMID- 18318253
TI  - [Case of macrolide-ineffective Mycoplasma pneumoniae pneumonia successfully
      treated with intravenous ciprofloxacin].
AB  - A 18-year-old man complaining of remittent fever and nonproductive cough visited
      a nearby clinic. He did not recover despite treatment of oral azithromycin. We
      admitted him because his chest radiograph showed consolidation in the left upper
      lung field. We diagnosed his pneumonia as co-infection by non-bacterial and
      bacterial pathogens, and initiated treatment with intravenous ampicillin and oral
      clarithromycin. On the 3rd day after admission his symptom had not improved, so
      his treatment was changed to intravenous panipenem/betamipron and erythromycin.
      Ciprofloxacin was administered intravenously because consolidative shadows with
      atelectasis increased on the chest radiograph on the 6th day. Clinical symptoms
      such as fever, CRP and chest radiograph findings were rapidly improved after the
      start of ciprofloxacin treatment. He was discharged on the 22nd hospital day.
      Since serum antibody titer against Mycoplasma pneumoniae was elevated to x 20,480
      on the 13th hospital day, it is confirmed that causative pathogen was macrolide
      ineffective Mycoplasma Pneumoniae.

PMID- 18318254
TI  - [Case of nonspecific interstitial pneumonia associated with aortitis syndrome].
AB  - A 32-year-old woman was admitted to our hospital because of fever and back pain.
      Two months previously, she had been given a diagnosis of bacterial pneumonia
      based on the same symptoms and recovered after antibiotic treatment. Chest CT
      scans on admission showed a consolidation and thickened pleura in the right lower
      lobe. Bronchoalveolar lavage fluids showed an alveolar hemorrhage. Lung biopsy
      specimens showed thickened pulmonary arteries and fibrotic nonspecific
      interstitial pneumonia (NSIP). Three years later, she was admitted with fever and
      pain of the left arm and aortitis syndrome was diagnosed. In this case of NSIP
      pattern associated with aortitis syndrome we speculate that repeated pulmonary
      infarction and alveolar hemorrhages caused the NSIP pattern.

PMID- 18318255
TI  - [Case of bilateral chylothorax with systemic lupus erythematosus complicated by
      steroid-/immunosuppressant-resistant pleural effusion].
AB  - A 20-year-old woman, with systemic lupus erythmatosus complicated by steroid-and
      immunosuppressant-resistant bilateral pleural effusion, was admitted to the
      emergency room because of dyspnea and fever. Chest Xray film revealed bilateral
      massive pleural effusion. Bilateral thoracocentesis yielded fluid with chyle.
      Conservative treatment including intravenous hyper-alimentation and continuous
      drainage were performed but with no remarkable improvement. She underwent
      thoracoscopy-aided ligation of the thoracic duct. After the operation, bilateral
      pleurodesis was performed by intrathoracic injection of OK-432, because of
      uncontrolled pleural effusion. There have been no signs of recurrence at 10
      months in this case of SLE with steroid-and immunosuppressant-resistant pleural
      effusion.

PMID- 18318256
TI  - [Case of broncholithiasis lithoptysis occurring spontaneously after repeated
      pneumonia].
AB  - An abnormal chest shadow was pointed out in a 56-year-old woman in a health check
      in 2001. She had pulmonary tuberculosis at age 11. Because of repeated fever for
      the previous 2 years, she visited our hospital in 2003 and right upper lobe
      pneumonia was detected with a calcified nodule that completely obstructed the
      right upper lobe bronchus on CT. After admission, she spontaneously expectorated
      a stone. The composition of the stone was 57% calcium phosphate and 43% calcium
      carbonate. Radiological findings and the composition of the stone suggested that
      this broncholith was calcified bronchial mucus rather than a calcified lymph node
      that might have perforated into the airway. Bronchiectasis of the right B3
      broncus was observed on CT scan after lithoptysis. Although the bronchiectasis
      was unchanged 2 years later, she had no symptoms, such as fever or cough.

PMID- 18318257
TI  - [Case of malignant lymphoma associated with rheumatoid arthritis].
AB  - A 72-year-old woman was admitted to our hospital with exacerbation of dyspnea.
      She had a history of rheumatoid arthritis (RA) for 26 years, and had been taking
      methotrexate and prednisolone. Chest radiograph and chest CT revealed marked
      mediastinal and right axillary lymph node swelling, interstitial shadows and
      bilateral pleural effusion. A biopsy of the right axillary lymph node for
      histopathological examination revealed diffuse large B cell lymphoma. The patient
      achieved complete remission, following 7 cycles of chemotherapy (R-EPOCH). As RA
      is associated with an increased risk of developing lymphoma, malignant lymphoma
      must be considered as a possible cause of the mediastinal swelling in a patient
      with RA.

PMID- 18318258
TI  - [Case of acute eosinophilic pneumonia probably induced by minocycline].
AB  - We reported a case of acute eosinophilic pneumonia (AEP) induced by minocycline.
      A 55-year-old man presented with a low grade fever and cough and was treated with
      antibiotics, including minocycline (MINO). During treatment, the patient
      developed symptoms of acute respiratory failure, and computed tomography (CT)
      scan showed bilateral ground grass opacities. Bronchoalveolar lavage (BAL) was
      performed. The percentage of eosinophils in the BAL fluid was elevated (66%). The
      patient was treated with methylprednisolone under a diagnosis of AEP. Immediately
      after initiation of therapy, the CT film findings and clinical symptoms improved.
      Although a drug-induced lymphocyte stimulation test for MINO was negative, we
      speculated that AEP was caused by MINO in this case.

PMID- 18318259
TI  - [Case of acute bird fancier's lung caused by a yellow-shouldered Amazon bird
      associated with lung cancer].
AB  - A 69-year-old man was admitted to our hospital complaining of generalized
      weakness and cough for one month. Chest computed tomography (CT) demonstrated
      bilateral ground-glass opacities and a nodule in right S6 about 11mm in diameter
      with multiple mediastinal lymph node swellings. After admission the patient's
      symptoms improved without therapy and examination of the bronchoalveolar lavage
      fluid (BALF) and transbronchial lung biopsy (TBLB) revealed findings compatible
      with acute hypersensitivity pneumonitis. We did not consider that the acute
      hypersensitivity was caused by the patient's Amazon bird, because he had been
      breeding them for 40 years. However after obtaining a careful history, it became
      clear that close and frequent contact with the bird had occurred for the first
      time in the previous year. On the basis of the anti-bird excreta antibody found
      in the patient's serum and BALF, we diagnosed this case as a case of acute bird
      fancier's lung caused by the yellow-shouldered Amazon bird. We diagnosed the
      nodule in right S6 as lung adenocarcinoma by a thoracoscopic lung biopsy, and
      performed lower lobe lobectomy. We considered that the mediastinal lymph node
      swellings were caused by hypersensitivity pneumonitis.

PMID- 18318260
TI  - [Case of pulmonary MALT lymphoma with follow-up imaging for 10 years].
AB  - Although abnormal shadow in the left upper lung of an 84-year-old male patient
      was confirmed in an examination in November 1996, follow-up observation was
      discontinued. In July 2006, he first visited our department with a chief
      complaint of shortness of breath, and was hospitalized because of an abnormal
      shadow in the left upper lung field and left pleural effusion. Since atypical
      lymphocytes were found in the pleural effusion, and positive cellular surface
      markers CD19 and 20, and chromosomal aberration of t (11 ; 18) (q22 ; q21) were
      confirmed, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
      tissue (MALT lymphoma) was diagnosed. Transbronchial lung biopsy of the left
      upper lobe confirmed small lymphocyte-like cellular infiltration, as seen in the
      pleural effusion, and CD20 immunostaining was positive, leading to the diagnosis
      of MALT lymphoma. In addition, serum immunoelectrophoresis demonstrated the
      development of macroglobulinemia as a complication. This case is valuable as
      changes diagnostic image over 10 years can be compared.

PMID- 18318261
TI  - [Spontaneous mediastinal and retroperitoneal hematoma caused by trauma in an
      patient receiving anticoagulation treatment].
AB  - An 80-year-old man had chest and abdominal pains after he fell and twisted his
      body. He was taking anticoagulant drugs as a precautionary measure to prevent
      stroke. His chest CT and MRI was taking the presence of a sandglass-like
      nonenhanced shadow extending from the retromediastinum to the retroperitneum. No
      mediastinal tumor was detected by gastroscopy or on a chest CT 6 months later.
      Although the patient gradually became anemic, his vital signs remained normal
      throughout his hospital stay. The shadow decreased following conservative
      treatment by transthoracic drainage. We suspect that this tumor was a spontaneous
      hematoma caused by trauma in a patient receiving anticoagulation treatment.

PMID- 18318262
TI  - [Cyclooxygenase 2 derived lipid mediators play a pivotal role in resolution of
      acute lung injury].

PMID- 18318263
TI  - [Analysis of bronchial asthma development and receptivity. A strategy for
      prevention of bronchial remodeling].

PMID- 18318264
TI  - [Analysis of chromatin modification in A549 cells].

PMID- 18318265
TI  - [Preparation and effect of a behavioral science-based education program for sleep
      improvement among medical students].
AB  - OBJECTIVE: The present study aimed to investigate a simple education program that
      is effective for sleep improvement among medical students who will be medical
      doctors in the future. The education program applied in the present study was
      developed for sleep improvement based on behavioral science and changes in
      knowledge and sleeping habits were observed. METHODS: Subjects were 6th-year
      medical students of 2002 and 2003. Students of 2002 attended a program including
      a 90-minute lecture and a 2-week practice learning session, and students of 2003
      attended only the lecture. In the lecture, behavior therapy for chronic insomnia
      was explained using a booklet. In the practice learning session, students set a
      target behavior for improvement and conducted self-monitoring of their sleep and
      the targeted behavior. Changes in knowledge about sleep, attitude toward the
      therapy, sleep, and sleep-related habits were observed and compared between the 2
      groups of subjects immediately and 2-weeks after the lecture. RESULTS: It was
      found that after both programs subjects had more knowledge about sleep than
      before. In the program including practice learning session, subjects' attitude
      for managing patients changed from before the lecture to after the lecture, and
      after the practice learning session. It was found that more than half of the
      students thought that they could provide sleep guidance based on the behavior
      therapy. Regarding the subjects' sleep, significant improvements were observed
      for "having nightmares upon falling asleep," "sleepiness during daytime," "sense
      of getting a sound sleep," and "mood upon waking up." Regarding sleep-related
      habits, significant improvements were observed for "taking a nap," "dozing off,"
      and "eating breakfast." On the other hand, only the lecture subjects improved
      irregularity of bedtime and sleeping time. Although an increase in knowledge and
      improvement of sleep were observed among students who attended only the lecture,
      a further increase in knowledge and improvement of sleeping habits were observed
      among students who also attended the practice learning session. CONCLUSION: The
      results described herein suggest developing and providing a simple and convenient
      education program for sleep improvement was effective for increasing students'
      knowledge about sleep, developing improved coping methods regarding sleep, and
      improving sleep. It is also suggested that behavioral scientific instructive
      methods, including practice learning, are effective for medical education.

PMID- 18318266
TI  - [Analyzing physical fitness by age and gender among healthy individuals in
      Fukuoka City].

PMID- 18318267
TI  - [Study on pricing and uptake rate of influenza vaccination for the elderly in
      Japan with a simple random sampling method].
AB  - PURPOSE: In 2001, Japan launched a nationwide subsidy program for influenza
      immunization of the elderly, whose implementation was devolved to municipalities.
      Rapid appraisal of the financial impact and utilisation are helpful for
      evaluating public programs. The government appraised uptake rate with a resource
      consuming complete survey. In the present study, the authors carried out a simple
      and easy sample survey, with a simple random sampling method, to estimate
      averages of co-payment, subsidy, and total price for one vaccination. The utility
      of a simple random sampling method for a nationwide survey is also discussed.
      METHOD: A total of 300 individuals were randomly selected from about 22 million
      senior citizens in the 2001/2 season. A questionnaire is sent to their municipal
      authorities, inquiring about the price of vaccination, the target population
      size, and the numbers of vaccinated seniors from 2001/2 to 2004/5. Annual changes
      and the differences between urban and rural areas were examined with analysis of
      variance and regression analysis. RESULTS: The response rate is 94.0%. Nationwide
      average prices of vaccination in terms of co-payment, subsidy, and total price
      changes from 2001/2 to 2004/5 were as follows: the co-payments were yen 1134, yen
      1136, yen 1139, yen 1129 and yen 1148; the subsidies were yen 2972, yen 2955, yen
      2966, yen 2954 and yen 2941; and the total prices are yen 4194, yen 4169, yen
      4178, yen 4156 and yen 4142. No statistically significant differences were found
      in the annual rates. Vaccine uptake rates from 2001/2 to 2003/4 were 29.9%,
      37.8%, 46.1%, 49.6%, showing a statistically significant increase. CONCLUSION:
      These are the first estimates of price and uptake rates of influenza vaccination
      for the elderly in Japan by a sample survey method. The results demonstrate that
      the co-payment, subsidies, and the total price have not changed significantly
      since the program started, but that uptake has improved. The results also suggest
      that simple random sampling methods are useful for rapid appraisal of the
      nationwide trends with public programs devolved to municipalities.

PMID- 18318268
TI  - [Relationships between smoking and eating habits or behavior in male students].
AB  - OBJECTIVE: The aim of this study was to investigate relationships between smoking
      and eating habits or behavior in male students. METHODS: We performed a
      questionnaire regarding smoking, eating habits, eating behavior, and the
      frequency of food intake for 277 male students. We also measured bone mass by a
      quantitative ultrasound device, along with height, weight, body fat, and gripping
      power. RESULTS: The percentage of students who had a smoking habit was 22.4%. No
      significant differences in physical factors between the smoker and non-smoker
      groups were observed. However, there was significant variation for having meals
      regularly, and for the habit of assessing their own eating behavior (both P <
      0.05). The percentage of students who wanted to obtain nutritional support for
      maintaining their health, or desiring nutritional support in order to keep a good
      body style was significantly lower in the smoker group compared to the non-smoker
      group (P < 0.05, respectively). Moreover, the percentage of students who had a
      habit of drinking alcohol or skipping meals was significantly higher in the
      smoker group (P = 0.002). In addition, the percentage of smoking students who had
      a habit of exercise was significantly lower (P < 0.001). CONCLUSION: In this
      study, we obtained useful data regarding relationships between smoking and eating
      habits in male students. These results suggested that appropriate nutritional
      education is important in the smoker group of male students for promotion of
      their health.

PMID- 18318269
TI  - [Related factors in the elderly's use of municipal institutions: basic study for
      promoting participation in a care prevention program].
AB  - PURPOSE: This study was performed to examine factors related to the use of
      municipal institutions with the focus on 'Accessibility'. METHOD: The data used
      in this analysis were from the AGES (Aichi Gerontological Evaluation Study)
      Project, conducted by Nihon Fukushi University located in Aichi Prefecture,
      Japan. A self-administrated questionnaires was mailed to 5,759 persons aged 65
      years and older who were not disabled in 2006, and 2,795 persons responded. A
      dependent variable in the analysis was the use of municipal institutions (a
      Public Health Center, Welfare Center for the elderly and City Hall). Independent
      variables were age, disease, employment status, IADL (instrumental activities of
      daily living), depression (GDS: geriatric depression scale), self-rated feeling
      of health and 'Accessibility' (transportation mode and distance from municipal
      institutions). Multivariate logistic analysis was used to provide adjusted
      relative risk estimates for the associations between use of municipal
      institutions and related factors. RESULTS: In multivariate logistic analysis,
      'Accessibility' showed a significant relative risk for the use of municipal
      institutions after controlling for other related factors. Compared with the
      elderly whose places of residence was located less than 250 meters from the
      municipal institutions, the relative risk for the elderly who resided more than
      1,500 meters from the municipal institutions was around 0.4 (male: RR = 0.358;
      female: RR = 0.378). CONCLUSION: 'Accessibility' is significantly related to the
      use of municipal institutions. To promote use of the municipal institutions,
      improving elderly access may well be effective.

PMID- 18318270
TI  - [Acute retinal necrosis--today, past and future].

PMID- 18318271
TI  - [Clinical neuro-ophthalmology of vision].
AB  - To diagnose a patient with a failing visual system, it is necessary to localize
      the site of the lesion in the system, and identify the etiology that has produced
      it. Physicians do not see diseases but just their manifestations. Clinical neuro
      ophthalmology provides the basic principles on how to progress from
      manifestations to the diseases they indicate. The Frank B. Walsh Neuro
      Ophthalmology Society (the Walsh Society) that originated in 1969 in the United
      States has been the center of clinical neuro-ophthalmology case studies
      throughout the world. In Japan, the Ronald M. Burde Clinical Neuro-Ophthalmology
      Study Group (the RMB Society) was organized in 2001 to establish and promote a
      clinicopathologic conference in the style of the Walsh Society. On this occasion,
      Prof. Burde was invited to the Annual Japanese Ophthalmological Society meeting.
      Based on some illustrative cases presented at the annual meetings of the RMB
      society, this review was carried out to present the current knowledge of clinical
      neuro-ophthalmology.

PMID- 18318272
TI  - [DNA microarray for ophthalmic research-- basic and clinical research].
AB  - The development of DNA microchip analysis continues to progress. This development
      provides us with new biological knowledge. DNA microchip analysis can be divided
      into expression profiling and genotyping. In infectious disease, DNA microchip
      analysis helps us to identify the pathogen.

PMID- 18318273
TI  - [Answered and unanswered questions regarding posterior segment complications in
      high myopia].
AB  - It has been challenging to treat high myopia-related macular diseases such as
      macular hole with retinal detachment (MHRD), myopic foveoschisis (MF), and myopic
      choroidal neovascularization (mCNV). Recent advances in basic and clinical
      research have enabled us to treat at least some of these cases. For instance,
      development of optical coherence tomography facilitates the diagnosis of MF, and
      MF has been found to precede MHRD formation. Vitrectomy with or without internal
      limiting membrane peeling is effective in treating MF and preventing consequent
      MHRD. Triamcinolone sub-Tenon injection and intravitreal bevacizumab is now
      widely used to treat mCNV. We attempt to address answered and unanswered
      questions regarding these diseases at present in order to understand the future
      tasks that we face.

PMID- 18318274
TI  - [Clinical features of acute retinal necrosis at Hokkaido University Hospital].
AB  - PURPOSE: To study clinical features of acute retinal necrosis (ARN) at Hokkaido
      University Hospital. METHODS: Twenty-one eyes of 19 patients with ARN (10 male
      and 9 female patients) who were treated at Hokkaido University Hospital between
      1992 and 2006 were retrospectively examined from clinical records. RESULTS: The
      average age of the patients was 53.4 years (range, 13 to 91 years). 17 cases were
      unilateral and 2 were bilateral. The pathogenic virus was herpes simplex virus-1
      (HSV-1) in 2 patients, and varicella-zoster virus (VZV) in 17 patients. Clinical
      severity was assessed from spreading speed and area of the retinal exudation, and
      5 eyes were judged as fulminant cases (4 VZV eyes, 1 HSV eye), 6 eyes as severe
      cases (6 VZV eyes), and 10 eyes as mild cases (9 VZV eyes, 1 HSV eye). The range
      of retinal exudation was 1 to 2 quadrants in 7 eyes, 3 to 4 quadrants in 3 eyes,
      and increased to all quadrants in 11 eyes. Retinal detachment (RD) was observed
      in 8 eyes (38%), and the final visual acuity was less than 0.1 in 9 eyes (43%).
      CONCLUSIONS: The leading cause of ARN at Hokkaido University Hospital was VZV,
      and no HSV-2 ARN was seen. Compared with other areas in Japan, ARN at Hokkaido
      University Hospital seems to show less frequent RD, but the same prognosis for
      final visual acuity.

PMID- 18318275
TI  - [Influence of vitrectomy for diabetic retinopathy on health-related quality of
      life].
AB  - PURPOSE: To evaluate the vision-related quality of life (QOL) in patients
      undergoing vitrectomy for diabetic retinopathy with the Japanese version of the
      25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25).
      SUBJECTS AND METHODS: Subjects were 87 patients undergoing vitrectomy for
      diabetic retinopathy of vitreous hemorrhage, macular edema, or fibrovascular
      membrane, only for the subject eye, or for subjects undergoing vitrectomy for the
      fellow eye within 6 months or later. The VFQ-25 date was recorded one month
      before and 6 months after the vitrectomy. The VFQ-25 data were compared before
      and after the vitrectomy. The subjects were classified by the pathological
      condition: 41 eyes with vitreous hemorrhage, 28 eyes with macular edema, and 18
      eyes with fibrovascular membrane. RESULTS: The average VFQ-25 scores of all the
      patients increased in almost all of the 12 subscales. Vitrectomy for vitreous
      hemorrhage was most effective in improving the VFQ-25 score, in improving 10 of
      the 12 subscales in the VFQ-25, and in increasing VFQ-25 scores to almost the
      same level as in phacoemulsification and foldable intraocular lens implantation
      for cataract patients in both eyes. CONCLUSION: NEI VFQ-25 quantitatively
      clarified that vitrectomy for diabetic retinopathy is effective in increasing the
      QOL of diabetic retinopathy patients.

PMID- 18318276
TI  - [Comparison in effectiveness of sterilization between chlorhexidine gluconate and
      povidone-iodine].
AB  - PURPOSE: To evaluate the positive value of bacterial cultures which were
      collected soon after various types of ophthalmic surgery, from eyelids and
      conjunctiva disinfected by dilute chlorhexidine gluconate or povidone-iodine
      solution. METHODS: This study evaluated 179 cases (mean age, 65.6 +/- 15.3) (210
      eyes) who underwent cataract surgery, vitrectomy and scleral buckling performed
      by the same surgeon between April 2005 and December 2005. We divided all the
      cases into two groups: cases whose eyelids and conjunctiva were disinfected with
      dilute 0.05% solution of chlorhexidine gluconate, and the other cases whose
      eyelids were disinfected with 10% solution of povidone-iodine, and the
      conjunctiva was treated with 16 times dilute povidone-iodine solution. Soon after
      surgery, samples for bacterial culture were scraped from all eyelids and
      conjunctiva by swabs. RESULTS: From the eyelids, bacteria were detected from 39
      of the 107 eyes in the chlorhexidine gluconate group, and 19 of the 103 eyes in
      the povidone-iodine group (p<0.01). There was no significant difference between
      the chlorhexidine gluconate and povidone-iodine groups with respect to the number
      of positive cases from the conjunctiva. However, a higher positive value in
      bacterial culture collected from eyelids was shown in the chlorhexidine gluconate
      group. CONCLUSIONS: Therefore, based on this result, we consider that povidone
      iodine solution has a superior disinfectant effect compared to chlorhexidine
      gluconate.

PMID- 18318277
TI  - Rapid testing of infection and disease states: the faster the better.

PMID- 18318278
TI  - Microfluidics at the crossroad with point-of-care diagnostics.
AB  - Microfluidic devices have been long advertised as a key candidate to
      revolutionize point-of-care (POC) diagnostics. Recent advances in this field have
      addressed some of the most important issues, which limited the deployment of
      microfluidic devices outside of clinical laboratories. This contribution
      discusses important technical and economic constraints that microfluidic products
      must overcome to be adopted by healthcare systems. Two sets of technologies are
      described which comply with the constraints of the POC environment. As such,
      these technologies illustrate a possible route for the development of
      microfluidic devices, which could fulfil the needs of clinicians for disease
      staging and monitoring.

PMID- 18318279
TI  - Sample preparation: a challenge in the development of point-of-care nucleic acid
      based assays for resource-limited settings.
AB  - Currently available nucleic acid testing (NAT)-based assays are complex and time
      consuming, and they require expensive instrumentation and dedicated laboratory
      spaces for sample preparation as well as for amplification and detection of the
      nucleic acid target. Reagents required for these tests are also expensive and
      must be transported and stored refrigerated or frozen. These characteristics have
      limited the use of such assays for point-of-care (POC) testing, especially in
      resource-poor settings. Efforts to develop simple and rapid NAT-based assays have
      focused predominantly on the amplification and detection steps, with sample
      preparation and nucleic acid extraction remaining the bottleneck in the
      development of NAT systems suitable for POC applications or resource-limited
      settings. A review of NAT platforms and technologies currently under development
      and validation for rapid field testing revealed that, in addition to requiring
      expensive and complex instrumentation, many of these systems also require off
      line sample preparation and reagent handling. In their current format, they are
      therefore not appropriate for POC testing in resource-limited settings. We
      evaluated several commercially available technologies and procedures for the
      isolation of nucleic acid with the extraction of HIV-1 RNA from human plasma as a
      model system. Our results indicate that solid-phase extraction with silica or
      glass in the presence of a chaotropic salt provides the highest extraction
      efficiency. However, none of the existing methods and technologies is readily
      adaptable to a POC system. The integration of sample preparation procedures well
      suited to NAT-based assays in resource-limited settings therefore remains a
      challenge.

PMID- 18318280
TI  - Quantitative assessment of human whole blood RNA as a potential biomarker for
      infectious disease.
AB  - Infection remains a significant cause of morbidity and mortality especially in
      newborn infants. Analytical methods for diagnosing infection are severely limited
      in terms of sensitivity and specificity and require relatively large samples. It
      is proposed that stringent regulation of the human transcriptome affords a new
      molecular diagnostic approach based on measuring a highly specific systemic
      inflammatory response to infection, detectable at the RNA level. This proposition
      raises a number of as yet poorly characterised technical and biological variation
      issues that urgently need to be addressed. Here we report a quantitative
      assessment of methodological approaches for processing and extraction of RNA from
      small samples of infant whole blood and applying analysis of variation from
      biochip measurements. On the basis of testing and selection from a battery of
      assays we show that sufficient high quality RNA for analysis using multiplex
      array technology can be obtained from small neonatal samples. These findings
      formed the basis of implementing a set of robust clinical and experimental
      standard operating procedures for whole blood RNA samples from 58 infants.
      Modelling and analysis of variation between samples revealed significant sources
      of variation from the point of sample collection to processing and signal
      generation. These experiments further permitted power calculations to be run
      indicating the tractability and requirements of using changes in RNA expression
      profiles to detect different states between patient groups. Overall the results
      of our investigation provide an essential first step toward facilitating an
      alternative way for diagnosing infection from very small neonatal blood samples,
      providing methods and requirements for future chip-based studies.

PMID- 18318281
TI  - SERS detection of environmental pollutants in humic acid-gold nanoparticle
      composite materials.
AB  - Humic acid (HA) solutions provide an unexpected medium for direct fabrication of
      gold nanoparticles (HA-AuNP) and a clear window for surface-enhanced Raman
      scattering (SERS) with many potential applications in the ultrasensitive chemical
      analysis of environmental pollutants. It is demonstrated that the HA-AuNP
      fabrication can be easily achieved in a wide range of pH (2 to 12). The
      background SERS spectra of HA is relatively weak in absolute intensity, allowing
      the detection of the enhanced Raman signal from trace amount of contaminants. An
      in-situ approach is illustrated where the HA-AuNP fabrication is carried out with
      a HA solution containing the target pollutant. The technique may allow for the
      direct detection of organic pollutants present in the humic fraction of soil.

PMID- 18318282
TI  - Separation and detection of individual submicron particles by capillary
      electrophoresis with laser-light-scattering detection.
AB  - Separation and detection of individual submicron polystyrene spheres using
      capillary electrophoresis with laser-light-scattering detection has been
      demonstrated. Electrophoretically separated particles were passed through a
      focused laser beam and light scattered from individual particles was collected at
      90 degrees. Each diameter of polystyrene spheres injected (from 110 to 992 nm)
      resulted in the observation of a well-defined migration window containing
      multiple peaks, each arising from the light scattered by an individual particle.
      The migration time window for individual particles of a particular size
      corresponded well to the migration time of a peak from a population of particles
      of the same size detected using a UV absorbance detector. The electrophoretic
      mobility and scattered light intensity were determined for each particle
      detected. The average scattered light intensity for each particle size was
      consistent with Mie scattering theory. Particles as small as 110 nm in diameter
      were detected individually using this method, but particles with a diameter of 57
      nm could not be individually detected. The number of single particle scattering
      events was counted and compared to the theoretical number of particles injected
      electrokinetically, and the detection efficiency determined ranged from 38 to 57%
      for polystyrene spheres of different sizes. The laser-light-scattering detection
      method was directly compared to laser-induced fluorescence detection using
      fluorescent polystyrene microspheres. The number of particles detected
      individually by each method was in agreement.

PMID- 18318283
TI  - Novel polymer composite to eliminate background matrix ions in matrix assisted
      laser desorption/ionization-mass spectrometry.
AB  - Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) is
      rarely used for the analysis of small molecules (< 700 Da) because the low m/z
      signal is overwhelmed by a high background of matrix ions. We have developed a
      solution to this problem that employs a novel polymer composite which is formed
      by covalently cross-linking alpha-cyano-4-hydroxycinnamic acid (HCCA) to SU-8
      photoresist via cationic photo-polymerization. Since the HCCA molecules are
      immobilized, background noise resulting from the matrix ions is significantly
      reduced or eliminated. Moreover, owing to the hydrophobic surface of the polymer
      film, the sample spots shrink during solvent evaporation and thus the analytes
      can be concentrated. As a result, this polymer composite improves detection
      sensitivity and extends the analyzable species to the low-mass region. The
      covalent incorporation of HCCA with SU-8 was validated with reflectance FTIR
      spectroscopy, and the polymer surface was characterized with scanning electron
      microscopy (SEM). Using MRFA, a small peptide as a standard, 8 mg of HCCA per mL
      of SU-8 photoresist was found to yield the highest sensitivity and the lowest
      background noise. Analytes such as peptides or small organic molecules were
      further examined on this composite surface and no analyte degradation was
      observed. In a trial of peptide mass fingerprinting of cytochrome c on the
      composite substrate, the inclusion of low m/z tryptic peptides in the database
      search dramatically improved the protein identification probability score.

PMID- 18318284
TI  - Empirical versus modelling approaches to the estimation of measurement
      uncertainty caused by primary sampling.
AB  - Measurement uncertainty is a vital issue within analytical science. There are
      strong arguments that primary sampling should be considered the first and perhaps
      the most influential step in the measurement process. Increasingly, analytical
      laboratories are required to report measurement results to clients together with
      estimates of the uncertainty. Furthermore, these estimates can be used when
      pursuing regulation enforcement to decide whether a measured analyte
      concentration is above a threshold value. With its recognised importance in
      analytical measurement, the question arises of 'what is the most appropriate
      method to estimate the measurement uncertainty?'. Two broad methods for
      uncertainty estimation are identified, the modelling method and the empirical
      method. In modelling, the estimation of uncertainty involves the identification,
      quantification and summation (as variances) of each potential source of
      uncertainty. This approach has been applied to purely analytical systems, but
      becomes increasingly problematic in identifying all of such sources when it is
      applied to primary sampling. Applications of this methodology to sampling often
      utilise long-established theoretical models of sampling and adopt the assumption
      that a 'correct' sampling protocol will ensure a representative sample. The
      empirical approach to uncertainty estimation involves replicated measurements
      from either inter-organisational trials and/or internal method validation and
      quality control. A more simple method involves duplicating sampling and analysis,
      by one organisation, for a small proportion of the total number of samples. This
      has proven to be a suitable alternative to these often expensive and time
      consuming trials, in routine surveillance and one-off surveys, especially where
      heterogeneity is the main source of uncertainty. A case study of aflatoxins in
      pistachio nuts is used to broadly demonstrate the strengths and weakness of the
      two methods of uncertainty estimation. The estimate of sampling uncertainty made
      using the modelling approach (136%, at 68% confidence) is six times larger than
      that found using the empirical approach (22.5%). The difficulty in establishing
      reliable estimates for the input variable for the modelling approach is thought
      to be the main cause of the discrepancy. The empirical approach to uncertainty
      estimation, with the automatic inclusion of sampling within the uncertainty
      statement, is recognised as generally the most practical procedure, providing the
      more reliable estimates. The modelling approach is also shown to have a useful
      role, especially in choosing strategies to change the sampling uncertainty, when
      required.

PMID- 18318285
TI  - Use of contactless conductivity detection for non-invasive characterisation of
      monolithic stationary-phase coatings for application in capillary ion
      chromatography.
AB  - A capacitively-coupled contactless conductivity detector (C4D) has been utilised
      as an on-capillary detector within a capillary ion chromatograph, incorporating a
      reversed-phase monolithic silica capillary column semi-permanently modified with
      a suitable ionic surfactant. The monolithic capillary column (150 x 0.1 mm i.d.)
      was modified using sodium dioctyl sulfosuccinate (DOSS), an anionic surfactant,
      for the separation of small inorganic and organic cations. With the use of the on
      capillary conductivity detector, the longitudinal homogeneity and temporal
      stability of the coating were investigated. The approach allowed a detailed non
      invasive observation of the nature of the ion-exchange coating over time, and an
      example of an application of the technique to produce a longitudinal stationary
      phase charge gradient is shown. An investigation of the basis of the measured on
      capillary conductivity was carried out with a counter ion study, clearly showing
      the on-capillary detection technique could also distinguish between chemical
      forms of the immobilised ion exchanger. The above method was used to produce a
      stable and homogeneously-modified monolithic ion-exchange capillary column, for
      application to the separation of inorganic alkaline earth cations and amino
      acids.

PMID- 18318286
TI  - Fabrication and evaluation of a 3-dimensional microchip device where carbon
      microelectrodes individually address channels in the separate fluidic layers.
AB  - A fabrication method that results in a 3-dimensional fluidic device containing
      poly(dimethylsiloxane) (PDMS) -embedded microelectrodes that individually address
      each layer is described. The two electrode-containing layers and the
      polycarbonate membrane are reversibly sealed together, eliminating the need for
      plasma oxidation during device assembly, while enabling simultaneous amperometric
      detection in membrane-separated fluidic channels. The electrodes were
      characterized using microchip-based flow analysis. It was found that PDMS
      embedded electrodes have a limit of detection (400 nM for catechol) that is 5
      fold lower than that reported for microchip-based flow analysis with similar
      electrodes in a hybrid PDMS-glass device. The selectivity of the carbon ink
      microelectrodes can be tuned by a simplified modification procedure; this was
      demonstrated by the selective detection of nitric oxide over possible
      interferents. Finally, the ability to monitor processes occurring in separate
      layers of a 3-dimensional device was shown by the simultaneous detection of
      catechol on either side of the polycarbonate membrane. The electrode response in
      each fluidic channel was found to be linear as a function of concentration and
      the transport between layers could be controlled by varying the linear velocities
      of each fluidic channel. The ability to fabricate and operate this type of 3
      dimensional device will be useful for the development of cell-based in vivo
      mimics that involve the transport of molecular messengers and/or pharmaceuticals
      across layers of immobilized cells.

PMID- 18318287
TI  - Electrochemically-assisted deposition of oxidases on platinum nanoparticle/multi
      walled carbon nanotube-modified electrodes.
AB  - Platinum nanoparticles were electrodeposited by a multi-potential step technique
      onto a multi-walled carbon nanotube (MWCNT) film pre-casted on a glassy carbon
      (GC) or boron-doped diamond (BDD) electrode. The MWCNT network consisted of Pt
      nanoparticles with an average diameter of 120 nm after an optimization of 36
      deposition cycles. The resulting electrochemical sensors were capable of
      detecting hydrogen peroxide as low as 25 nM. Five different enzymes: glucose,
      lactate, glutamate, amino acid and xanthine oxidases, respectively, were
      deposited by a constant current technique for 5-10 min to form a stable and
      active biolayer for the analysis of their corresponding analytes. The glucose
      oxidase-based biosensor was linear up to 10 mM glucose with a detection limit of
      250 nM and a response time of 5 s. Similar response times and detection limits
      were observed with glutamate, lactate, and amino acid oxidase despite the fact
      that the linear ranges were noticeably narrower. The mechanism of deposition was
      attributed to the decrease of local pH, created by oxygen evolution and effected
      enzyme precipitation.

PMID- 18318288
TI  - Water-compatible molecularly imprinted polymers for efficient direct injection on
      line solid-phase extraction of ropivacaine and bupivacaine from human plasma.
AB  - Two novel molecularly imprinted polymers (MIPs) selected from a combinatorial
      library of bupivacaine imprinted polymers were used for selective on-line solid
      phase extraction of bupivacaine and ropivacaine from human plasma. The MIPs were
      prepared using methacrylic acid as the functional monomer, ethylene glycol
      dimethacrylate as the cross-linking monomer and in addition
      hydroxyethylmethacrylate to render the polymer surface hydrophilic. The novel
      MIPs showed high selectivity for the analytes and required fewer and lower
      concentrations of additives to suppress non-specific adsorption compared with a
      conventional MIP. This enabled the development of an on-line system for direct
      extraction of buffered plasma. Selective extraction was achieved without the use
      of time-consuming solvent switch steps, and transfer of the analytes from the MIP
      column to the analytical column was carried out under aqueous conditions fully
      compatible with reversed-phase LC gradient separation of analyte and internal
      standard. The MIPs showed excellent aqueous compatibility and yielded extractions
      with acceptable recovery and high selectivity.

PMID- 18318289
TI  - Do we really need to account for run bias when producing analytical results with
      stated uncertainty? Comment on 'Treatment of bias in estimating measurement
      uncertainty' by G. E. O'Donnell and D. B. Hibbert.
AB  - Treatment of bias is an important issue relating to analytical quality. Recently,
      G. E. O'Donnell and D. B. Hibbert (Analyst, 2005, 130, 721) recommended to always
      correct analytical results for 'run bias' determined by a single analysis of a
      certified reference material (CRM) in each analytical run. In the authors'
      opinion, this is necessary for the results obtained to be comparable from run to
      run. It is argued here that such a recommendation is logically inconsistent and
      stems from misinterpretation of measurement uncertainty as being estimated under
      repeatability conditions. The fundamental principle underlying the measurement
      uncertainty methodology is that all relevant sources of error should be taken
      into account, which results in overall uncertainty assessment and thus provides a
      means for a global comparability of measurement and test results. The local, i.e.
      run-to-run, comparability is not a factor if analytical results are interpreted
      on the basis of their associated uncertainty.

PMID- 18318290
TI  - ["Being a psychiatric nurse has been completely political"].

PMID- 18318291
TI  - [Method of nursing employment].

PMID- 18318292
TI  - [Working harder in order to gain months in the hospital].

PMID- 18318293
TI  - [Care of rheumatic diseases].

PMID- 18318294
TI  - [Treatment of iliac arthritis].

PMID- 18318295
TI  - [Treatment of Dupuytren's contracture by injection].

PMID- 18318296
TI  - [The school of rheumatoid arthritis for a therapeutic education].

PMID- 18318297
TI  - [Rheumatism information in 100 questions].

PMID- 18318298
TI  - [Mercedes Chaboissier on the track of a contemporary nurse].

PMID- 18318299
TI  - [Responsibilities of a nurse].

PMID- 18318300
TI  - [Sharing experiences in mobile units].

PMID- 18318301
TI  - [Nurses and genetic counseling].

PMID- 18318302
TI  - [Attitude of society on sexuality in the aged].

PMID- 18318303
TI  - [What are the perspectives of choice among nursing students?].

PMID- 18318304
TI  - [Ambulatory bladder ultrasonography].

PMID- 18318305
TI  - [The art of nursing, portraits of the progress of women and men].

PMID- 18318306
TI  - [Joseph Carrere (1740-1802)].

PMID- 18318307
TI  - [Filgastim (G-CSF)].

PMID- 18318308
TI  - [Study of abnormal agglutinins].

PMID- 18318309
TI  - [Room for support for women].

PMID- 18318310
TI  - An accidental death.

PMID- 18318311
TI  - Call for ban on unsafe needles after inquest into nurse's death.

PMID- 18318312
TI  - U.S. candidates under the microscope over country's failing health care.

PMID- 18318313
TI  - The nurse told my 85-year-old mother she was obnoxious.
AB  - Experienced nurse Judith Allen was proud to be a nurse--at least she was before
      her elderly mother was admitted to hospital for the final time.

PMID- 18318314
TI  - Model for malaria.
AB  - A system of franchising health clinics is bringing health care and medicines to
      rural Kenya--and helping people to make a living.

PMID- 18318315
TI  - Nutrition now. Ripe for reform.
AB  - Levels of nutritional care for patients in the community are difficult to gauge,
      but community nurses can make a difference to those at risk.

PMID- 18318316
TI  - Help to let go.

PMID- 18318317
TI  - Intramuscular injection techniques.
AB  - The administration of intramuscular (IM) injections is an important part of
      medication management and a common nursing intervention in clinical practice. A
      skilled injection technique can make the patient's experience less painful and
      avoid unnecessary complications.

PMID- 18318318
TI  - Caring for older adults with learning disabilities.
AB  - Older patients with learning disabilities have greater physical and mental
      healthcare needs than the general population. However, because of a lack of
      knowledge about learning disabilities and low confidence in working with this
      patient group, their healthcare needs are often misinterpreted or neglected. By
      learning more about this group and developing skills that can aid the nurse
      patient relationship, nurses will become more confident in their working practice
      and older patients with learning disabilities can receive the same quality health
      service as other patients.

PMID- 18318319
TI  - Improving nutrition.

PMID- 18318320
TI  - Non-cancer-related lymphoedema of the lower limb.
AB  - Lymphoedema is an incurable, progressive condition causing pain, psychological
      distress and mobility difficulties. Excessive swelling, worsening skin breakdown
      and leakage of lymph adversely affect the patient's quality of life while also
      placing increasing demands on district nursing resources. This article reviews
      the prevalence of non-cancer-related lower limb lymphoedema, the patient
      experience, management of the condition and district nurses' knowledge in this
      area.

PMID- 18318321
TI  - Differences between acute and chronic wounds and the role of wound bed
      preparation.
AB  - There are major differences in the way acute and chronic wounds heal. An
      understanding of these differences enables practitioners to plan more appropriate
      care and management for patients. A simple framework such as wound bed
      preparation can be used to identify problems and plan realistic and appropriate
      outcomes of care.

PMID- 18318322
TI  - Older and wiser.

PMID- 18318323
TI  - Leaders at Liverpool.

PMID- 18318324
TI  - Stress busters.

PMID- 18318325
TI  - The nurse's role in discouraging clinical inertia in diabetes management:
      optimizing cardiovascular health among African-Americans.

PMID- 18318326
TI  - Examining racial and ethnic disparities and predictors of medication use among
      California's African-American, Latino, and White children with asthma.
AB  - The purpose of this study was to determine the factors that are associated with
      the use of prescription medication to control asthma in California's African
      American, Latino, and White children from 1 to 11 years of age. This was a
      secondary analysis of parental reports of the use of prescription medication by
      children with current asthma symptoms (defined as MD diagnosis of asthma). These
      children were identified from a cross-sectional survey called the California
      Health Interview Survey (CHIS), 2001. An overall sample of 1,313 children with
      current asthma was used in the study. It was found that African-American children
      were 1.85 times (95% CI: 1.82, 1.88) more likely than White children were and
      1.87 times (95% CI: 1.86, 1.90) more likely than Latino children to use
      prescription medication to control their asthma. Multivariate analysis showed an
      association with severity (mild, moderate, and severe symptoms), two childhood
      disability factors, and medication use. Asthma severity and disability (defined
      as affects to social role function) predicts the use of medications for African
      American, Latino, and White children with asthma in California.

PMID- 18318327
TI  - Community income, smoking, and birth weight disparities in Wisconsin.
AB  - This study examined the extent to which community-level income and smoking status
      were associated with birth-weight disparities in the state of Wisconsin. Data
      included 1998 and 1999 birth record files with appended census income data for
      African-American, Latino, and White single births in Wisconsin. Multinomial
      logistic regression analysis was performed where the dependent variable included
      low birth weight (LBW: < 2,500 grams) and very low birth weight (VLBW: < 1,500
      grams) relative to normal birth weight. The independent variables included income
      levels categorized as poor (< $12,499), lower middle ($12,500-34,999), and upper
      middle to affluent ($35,000 or more) determined by zip code, and smoking status
      (yes/no). African-American and Latino mothers who lived in poor communities and
      smoked were almost three times more likely to have a low birth weight (LBW)
      infant than their more affluent, non-smoking counterparts. Community income and
      smoking status played significant roles in birth weight disparities.

PMID- 18318328
TI  - A quick survey of an HBCU's first year nursing students' perception of the
      HIV/AIDS phenomenon.
AB  - There are always some assumptions that are made about the knowledge of the Human
      Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) phenomenon
      among graduating high school seniors. To ascertain their knowledge, a categorical
      survey questionnaire was designed featuring yes and no answers, a Likert scale,
      and qualitative response questions to the problem of HIV/AIDS prevention
      behavior. It was administered to first semester nursing college students at an
      historically black college and university (HBCU) in northeastern United States.
      These freshman students were enrolled in the course University Seminar. The class
      consisted of 68 students (64 females and 4 males). The students in this class
      anonymously completed the questionnaire about their perceptions and knowledge of
      the HIV/AIDS phenomenon. Findings from the study indicated that the majority of
      the students knew that HIV/AIDS could make an individual sick enough to die. The
      students stated, however, that they were willing to submit to the sexual demands
      of their partners, even when they refused to wear condoms. Of the 64 female
      students who responded to the questionnaire, 38 stated that using a condom might
      diminish their feeling during the sexual experience and they thought that it was
      very important that that did not happen. Therefore, this situation might affect a
      student's decision as to whether or not to insist on using a condom. In
      conclusion, it is recommended that intensive HIV/AIDS education be incorporated
      into the curriculum and the questionnaire be repeated in these students' junior
      and senior years to ascertain whether or not there was a change in their
      attitudes.

PMID- 18318329
TI  - Assessing knowledge of breast self exams in older African-American women.
AB  - Breast cancer mortality rates for older women increase dramatically with age.
      This descriptive study assessed the knowledge of breast self-exams (BSEs) via pre
      tests and post-tests in older African-American women (> 60) at an initial session
      (Time 1), and then again at a follow-up session (Time 2) two months later. A
      sample of 57 older African-American women living in inner city apartment
      buildings participated in the study. There were significant differences between
      pre-test Time 1 and post-test Time 1 (p = .000) and pre-test Time 2 and post-test
      Time 2 (p = .000). In addition, a significant difference was detected between pre
      test Time 1 and pre-test Time 2 (p = .039). Additionally, a content analysis
      revealed what factors would influence older African-American women to continue to
      perform BSEs in the future. Providing BSE education to older African-American
      women may be useful in decreasing mortality rates for breast cancer.

PMID- 18318330
TI  - Health-promoting behaviors of English-speaking Caribbean women in the United
      States.
AB  - The purpose of this study was to identify factors that influence the health
      promotion levels of female English-speaking Caribbean immigrants. A descriptive
      cross-sectional design was used to determine the impact of (a) ethnicity, (b)
      marital status, (c) country of origin, (d) level of education, (e) years since
      immigration, (f) yearly income, (g) placement of health locus-of-control, and (h)
      self-efficacy on the health-promotion levels of English-speaking Caribbean
      immigrants. A descriptive cross-sectional design was used to conduct this study,
      a survey instrument was used for data collection, and interpretation utilized
      descriptive statistics. The study participants were 206 women who were obtained
      from a convenience sample of Caribbean associations and who responded to
      questionnaires. Analysis of data included descriptive and inferential statistics.
      Results from the analysis indicated that a higher level of education and
      increased self-efficacy were predictors of higher levels of health promotion
      among female Caribbean immigrants. Recommendations are for larger and broader
      cross-sectional studies of Caribbean immigrants. It is also recommended that
      health-promotion interventions be targeted towards those who have recently
      immigrated to the United States. Further research is needed to continue to
      investigate the processes behind the likelihood of participation in health
      promotion behavior.

PMID- 18318331
TI  - Patient perspectives on disparities in healthcare from African-American, Asian,
      Hispanic, and Native American samples including a secondary analysis of the
      Institute of Medicine focus group data.
AB  - The existence of racial and ethnic disparities in healthcare in the United States
      is well recognized. However, often overlooked in the planning and design of
      initiatives to address those disparities are the patient perspectives regarding
      the issues of racial and ethnic disparities that directly affect them. The
      objective of this study was to identify the patient priorities and to provide
      recommendations for action to improve minority health-care quality. A secondary
      objective was the qualitative analysis of the Institute of Medicine (IOM) focus
      group data. Six focus groups were conducted with nine participants in each. These
      included an African-American focus group in Washington, D.C., an African-American
      focus group in Los Angeles, an Asian focus group in Los Angeles, an Hispanic
      focus group in Washington, D.C., an Hispanic focus group in Los Angeles, and a
      Native American focus group in Albuquerque, NM. The barriers and priorities for
      action included difficulty in making informed choices when identifying and
      selecting providers, poor service delivery from medical office staff, the
      inefficiency of medical visits, provider communication and cultural competence
      barriers, and stressful treatment settings. Patient recommendations targeted
      provision of tools to empower patients throughout the process of care, provider
      and staff training in communication and cultural competence, alternate models of
      service delivery, and accessible mechanisms for evaluation and oversight. This
      study concluded that patient-identified priorities and recommendations warranted
      modification of current explanatory models for minority health-care quality and
      the provision of greater clarity regarding directions for policy and behavioral
      initiatives and criteria for performance evaluation be advanced.

PMID- 18318332
TI  - Promoting breast health among women in the U.S. Virgin Islands: a focused study
      of the needs of Caribbean women.
AB  - Breast cancer is the number one cause of cancer death among women in the United
      States Virgin Islands. Consequently, the Bureau of Health has identified breast
      cancer as a priority health concern. Within the medical community, increasing
      emphasis is being placed on the importance of hereditary, familial,
      environmental, and behavioral risk factors to breast cancer control. Little
      research has been conducted regarding these factors, however, to explore their
      influence on breast cancer detection and breast cancer risk management. This
      report highlights the outcomes of a study undertaken to explore the associations
      between breast cancer risk, risk assessment, risk communication, screening, and
      receptivity to the management of breast cancer risk among women from the United
      States Virgin Islands. Results of this study suggest a need within the territory
      to expand the systems that are responsible for monitoring and reporting breast
      cancer trends; forums to discuss concerns of women relative to breast health;
      forums to discuss communication with health-care providers; and, research efforts
      that address breast cancer detection and control among women in the United States
      Virgin Islands.

PMID- 18318333
TI  - Racial disparities in access to care within the cardiac revascularization
      population.
AB  - Health disparities and vulnerability are embedded within the context of
      historical and contemporary dynamics, and are confounded by inequities in access
      to quality healthcare. Early management and preventive therapy has been the
      cornerstone of cardiovascular medicine for acute coronary syndromes. Invasive
      cardiac strategies, including revascularization with percutaneous coronary
      intervention or coronary artery bypass grafting have been instituted as methods
      to minimize subsequent cardiovascular events and to improve survival benefits.
      Several studies have described the obstacles and variance involved in the
      distribution of access to cardiac catheterization, particularly among vulnerable
      groups such as African-Americans. There is a paucity of nursing research in the
      area of access to care and cardiovascular disease. The purpose of this article is
      to examine the existing nature of disparities in health-care access among ethnic
      minority cardiac populations who utilize or require invasive cardiac procedures.
      This will be followed by an exploration of avenues to which nursing science can
      make substantial contributions.

PMID- 18318334
TI  - The incidence of cardiovascular disease in menopausal women on hormone
      replacement therapy: a clinical evidence-based medicine review.
AB  - Postmenopausal women have looked to the scientific and medical community for
      conclusions on the effects of hormone replacement therapy (HRT) on cardiovascular
      disease. There have been many studies and clinical trials conducted in an attempt
      to address whether or not there is increased incidence of cardiovascular disease
      (CVD) among postmenopausal women on HRTs. The results of the Women Health
      Initiative study on HRTs and CVD have concluded that HRTs have no protective
      effect on the cardiovascular system. It has been suggested that HRTs may even
      promote the development of a cardiovascular event. Many researchers and members
      of the health-care community have disputed these claims. These opposing views
      have fostered more research in an attempt to draw a consensus in this debate.
      This clinical review examines evidence-based medical research literature and
      provides an overview of the outcomes.

PMID- 18318335
TI  - Advances in integrated and continuous measurements for particle mass and chemical
      composition.
AB  - Recent improvements in integrated and continuous PM2.5 mass and chemical
      measurements from the Supersite program and related studies in the past decade
      are summarized. Analytical capabilities of the measurement methods, including
      accuracy, precision, interferences, minimum detectable levels, comparability, and
      data completeness are documented. Upstream denuders followed by filter packs in
      integrated samplers allow an estimation of sampling artifacts. Efforts are needed
      to: (1) address positive and negative artifacts for organic carbon (OC), and (2)
      develop carbon standards to better separate organic versus elemental carbon (EC)
      under different temperature settings and analysis atmospheres. Advances in
      thermal desorption followed by gas chromatography/ mass spectrometry (GC/MS)
      provide organic speciation of approximately 130 nonpolar compounds (e.g., n
      alkanes, alkenes, hopanes, steranes, and polycyclic aromatic hydrocarbons [PAHs])
      using small portions of filters from existing integrated samples. Speciation of
      water-soluble OC (WSOC) using ion chromatography (IC)-based instruments can
      replace labor-intensive solvent extraction for many compounds used as source
      markers. Thermal gas-based continuous nitrate and sulfate measurements
      underestimate filter ions by 10-50% and require calibration against on-site
      filter-based measurements. IC-based instruments provide multiple ions and report
      comparable (+/-10%) results to filter-based measurements. Maintaining a greater
      than 80% data capture rate in continuous instruments is labor intensive and
      requires experienced operators. Several instruments quantify black carbon (BC) by
      optical or photoacoustic methods, or EC by thermal methods. A few instruments
      provide real-time OC, EC, and organic speciation. BC and EC concentrations from
      continuous instruments are highly correlated but the concentrations differ by a
      factor of two or more. Site- and season-specific mass absorption efficiencies are
      needed to convert light absorption to BC. Particle mass spectrometers, although
      semiquantitative, provide much information on particle size and composition
      related to formation, growth, and characteristics over short averaging times.
      Efforts are made to quantify mass by collocating with other particle sizing
      instruments. Common parameters should be identified and consistent approaches are
      needed to establish comparability among measurements.

PMID- 18318336
TI  - Continuous and semicontinuous monitoring techniques for particulate matter mass
      and chemical components: a synthesis of findings from EPA's Particulate Matter
      Supersites Program and related studies.
AB  - The U.S. Environmental Protection Agency (EPA) established the Particulate Matter
      (PM) Supersites Program to provide key stakeholders (government and private
      sector) with significantly improved information needed to develop effective and
      efficient strategies for reducing PM on urban and regional scales. All Supersites
      projects developed and evaluated methods and instruments, and significant
      advances have been made and applied within these programs to yield new insights
      to our understanding of PM accumulation in air as well as improved source
      receptor relationships. The tested methods include a variety of continuous and
      semicontinuous instruments typically with a time resolution of an hour or less.
      These methods often overcome many of the limitations associated with measuring
      atmospheric PM mass concentrations by daily filter-based methods (e.g., potential
      positive or negative sampling artifacts). Semicontinuous coarse and ultrafine
      mass measurement methods also were developed and evaluated. Other semicontinuous
      monitors tested measured the major components of PM such as nitrate, sulfate,
      ammonium, organic and elemental carbon, trace elements, and water content of the
      aerosol as well as methods for other physical properties of PM, such as number
      concentration, size distribution, and particle density. Particle mass
      spectrometers, although unlikely to be used in national routine monitoring
      networks in the foreseeable future because of their complex technical
      requirements and cost, are mentioned here because of the wealth of new
      information they provide on the size-resolved chemical composition of atmospheric
      particles on a near continuous basis. Particle mass spectrometers likely
      represent the greatest advancement in PM measurement technology during the last
      decade. The improvements in time resolution achieved by the reported
      semicontinuous methods have proven to be especially useful in characterizing
      ambient PM, and are becoming essential in allowing scientists to investigate
      sources of particulate pollution and to probe into the dynamics and mechanisms of
      aerosol formation in the atmosphere.

PMID- 18318337
TI  - Transport of atmospheric fine particulate matter: part 2--findings from recent
      field programs on the intraurban variability in fine particulate matter.
AB  - Air quality field data, collected as part of the fine particulate matter
      Supersites Program and other field measurements programs, have been used to
      assess the degree of intraurban variability for various physical and chemical
      properties of ambient fine particulate matter. Spatial patterns vary from nearly
      homogeneous to quite heterogeneous, depending on the city, parameter of interest,
      and the approach or method used to define spatial variability. Secondary
      formation, which is often regional in nature, drives fine particulate matter mass
      and the relevant chemical components toward high intraurban spatial homogeneity.
      Those particulate matter components that are dominated by primary emissions
      within the urban area, such as black carbon and several trace elements, tend to
      exhibit greater spatial heterogeneity. A variety of study designs and data
      analysis approaches have been used to characterize intraurban variability. High
      temporal correlation does not imply spatial homogeneity. For example, there can
      be high temporal correlation but with spatial heterogeneity manifested as smooth
      spatial gradients, often emanating from areas of high emissions such as the urban
      core or industrial zones.

PMID- 18318338
TI  - Synopsis of the temporal variation of particulate matter composition and size.
AB  - A synopsis of the detailed temporal variation of the size and number distribution
      of particulate matter (PM) and its chemical composition on the basis of
      measurements performed by several regional research consortia funded by the U.S.
      Environmental Protection Agency (EPA) PM Supersite Program is presented. This
      program deployed and evaluated a variety of research and emerging commercial
      measurement technologies to investigate the physical and chemical properties of
      atmospheric aerosols at a level of detail never before achieved. Most notably
      these studies demonstrated that systematic size-segregated measurements of mass,
      number, and associated chemical composition of the fine (PM2.5) and ultrafine
      (PM0.1) fraction of ambient aerosol with a time resolution down to minutes and
      less is achievable. A wealth of new information on the temporal variation of
      aerosol has been added to the existing knowledge pool that can be mined to
      resolve outstanding research and policy-related questions. This paper explores
      the nature of temporal variations (on time scales from several minutes to hours)
      in the chemical and physical properties of PM and its implications in the
      identification of PM formation processes, and source attribution (primary versus
      secondary), the contribution of local versus transported PM and the development
      of effective PM control strategies. The PM Supersite results summarized indicate
      that location, time of day, and season significantly influence not only the mass
      and chemical composition but also the size-resolved chemical/elemental
      composition of PM. Ambient measurements also show that ultrafine particles have
      different compositions and make up only a small portion of the PM mass
      concentration compared with inhalable coarse and fine particles, but their number
      concentration is significantly larger than their coarse or fine counterparts. PM
      size classes show differences in the relative amounts of nitrates, sulfates,
      crustal materials, and most especially carbon as well as variations in seasonal
      and diurnal patterns.

PMID- 18318339
TI  - Secondary particulate matter in the United States: insights from the Particulate
      Matter Supersites Program and related studies.
AB  - Secondary aerosols comprise a major fraction of fine particulate matter (PM2.5)
      in all parts of the country, during all seasons, and times of day. The most
      abundant secondary species include sulfate, nitrate, ammonium, and secondary
      organic aerosols (SOAs). The relative abundance of each species varies in space
      and time as a function of meteorology, source emissions strength and type,
      thermodynamics, and atmospheric processing. Transport of secondary aerosols from
      upwind locations can contribute significantly at downwind receptor sites,
      especially regionally in the eastern United States, and across a given urbanized
      area, such as in Los Angeles. Processes governing the formation of the inorganic
      secondary species (sulfate, nitrate, and ammonium) are fairly well understood,
      although the occurrence of nucleation bursts initiated with the formation of
      ultrafine sulfuric acid particles observed regionally on clean days in the
      eastern United States was unexpected. Because of the complex nature of organic
      material in air, much is still to be learned about the sources, formation, and
      even spatial and temporal distributions of SOAs. For example, a considerable
      fraction of ambient organic PM is oxidized organic species, many of which still
      need to be identified, quantified, and their sources and formation mechanisms
      determined. Furthermore, significant uncertainty (approaching 50% or more) is
      associated with estimating the SOA fraction of organic material in air with
      current methods. This review summarizes the findings of the Supersites Program
      and related studies addressing secondary particulate matter (PM), including
      spatial and temporal variations of secondary PM and its precursor species, data
      and methods for determining the primary and secondary fractions of PM mass, and
      findings on the anthropogenic and natural fractions of secondary PM.

PMID- 18318340
TI  - Transport of atmospheric fine particulate matter: part 1--findings from recent
      field programs on the extent of regional transport within North America.
AB  - Air quality field data, collected as part of the fine particulate matter
      Supersites program and other field measurements programs, have been used to
      assess the role of aerosol transport, over length scales of approximately 100
      1000 km, on fine particulate matter concentrations. Assessment of data from New
      York, NY; Baltimore, MD; Pittsburgh, PA; Atlanta, GA; Houston, TX; St. Louis, MO;
      and Fresno, CA, indicates that in virtually all of the regions, transport of
      aerosol over distances of 100-1000 km has a significant impact on urban
      particulate matter concentrations and a dominant role in determining rural
      particulate matter concentrations, though the nature of the regional
      contributions differs from region to region. This assessment is generally
      consistent with previous conceptual models of fine particulate matter formation
      and accumulation in these regions. The nature of the transported aerosol is
      largely sulfate in Eastern and Midwestern cities and nitrate in the Central
      Valley of California. In addition to physical transport of aerosol over distances
      of 100-1000 km, regional transport of aerosol precursors may lead to conditions
      conducive to large-scale nucleation events. Regional nucleation events have been
      reported in the East, Midwest, and in California. The events occurred in the
      morning soon after surface layers coupled with layers aloft, and the events
      generate ultrafine particles. In some cases, these nucleation events have been
      correlated with availability of sulfur dioxide and, therefore, may be sulfate
      formation events.

PMID- 18318341
TI  - Source apportionment: findings from the U.S. Supersites Program.
AB  - Receptor models are used to identify and quantify source contributions to
      particulate matter and volatile organic compounds based on measurements of many
      chemical components at receptor sites. These components are selected based on
      their consistent appearance in some source types and their absence in others.
      UNMIX, positive matrix factorization (PMF), and effective variance are different
      solutions to the chemical mass balance (CMB) receptor model equations and are
      implemented on available software. In their more general form, the CMB equations
      allow spatial, temporal, transport, and particle size profiles to be combined
      with chemical source profiles for improved source resolution. Although UNMIX and
      PMF do not use source profiles explicitly as input data, they still require
      measured profiles to justify their derived source factors. The U.S. Supersites
      Program provided advanced datasets to apply these CMB solutions in different
      urban areas. Still lacking are better characterization of source emissions, new
      methods to estimate profile changes between source and receptor, and systematic
      sensitivity tests of deviations from receptor model assumptions.

PMID- 18318342
TI  - EPA Supersites Program-related emissions-based particulate matter modeling:
      initial applications and advances.
AB  - One objective of the U.S. Environmental Protection Agency's (EPA's) Supersite
      Program was to provide data that could be used to more thoroughly evaluate and
      improve air quality models, and then have those models used to address both
      scientific and policy-related issues dealing with air quality management. In this
      direction, modeling studies have used Supersites-related data and are reviewed
      here. Fine temporal resolution data have been used both to test model components
      (e.g., the inorganic thermodynamic routines) and air quality modeling systems (in
      particular, Community Multiscale Air Quality [CMAQ] and Comprehensive Air Quality
      Model with extensions [CAMx] applications). Such evaluations suggest that the
      inorganic thermodynamic approaches being used are accurate, as well as the
      description of sulfate production, although there are significant uncertainties
      in production of nitric acid, biogenic and ammonia emissions, secondary organic
      aerosol formation, and the ability to follow the formation and evolution of
      ultrafine particles. Model applications have investigated how PM levels will
      respond to various emissions controls, suggesting that nitrate will replace some
      of the reductions in sulfate particulate matter (PM), although the replacement is
      small in the summer. Although not part of the Supersite program, modeling being
      conducted by EPA, regional planning organizations, and states for policy purposes
      has benefited from the detailed data collected, and the PM models have advanced
      by their more widespread use.

PMID- 18318343
TI  - What have we learned from highly time-resolved measurements during EPA's
      Supersites Program and related studies?
AB  - A wide range of new and exciting highly time-resolved instruments were deployed
      during the U.S. Environmental Protection Agency (EPA) Supersite program and
      related studies that occurred during the same time period. These measurements
      elucidated the temporal variation of a suite of gas-phase species, particle
      physical properties, and size-resolved particulate chemical composition. Because
      the temporal resolution was so high, concentration and size distribution changes
      as short as 1 min or less were discerned. Often data from multiple instruments
      were correlated with each other and with meteorological measurements, and these
      correlations enabled conclusions to be drawn about the photochemical activity of
      the atmosphere, the location of point sources, and even the emissions
      characteristics of these sources. For instance, rapid changes in particulate
      matter (PM) concentration were due to meteorological conditions, emissions, and
      plume excursions that led to increases in nitrate, sulfate, and organic carbon
      concentrations. This paper summarizes the conclusions that have been reached, to
      date, using these new, highly time-resolved instruments, and demonstrates their
      promise for future studies.

PMID- 18318344
TI  - Fine particulate matter emissions inventories: comparisons of emissions estimates
      with observations from recent field programs.
AB  - Emissions inventories of fine particulate matter (PM2.5) were compared with
      estimates of emissions based on data emerging from U.S. Environment Protection
      Agency Particulate Matter Supersites and other field programs. Six source
      categories for PM2.5 emissions were reviewed: on-road mobile sources, nonroad
      mobile sources, cooking, biomass combustion, fugitive dust, and stationary
      sources. Ammonia emissions from all of the source categories were also examined.
      Regional emissions inventories of PM in the exhaust from on-road and nonroad
      sources were generally consistent with ambient observations, though uncertainties
      in some emission factors were twice as large as the emission factors. In
      contrast, emissions inventories of road dust were up to an order of magnitude
      larger than ambient observations, and estimated brake wear and tire dust
      emissions were half as large as ambient observations in urban areas. Although
      comprehensive nationwide emissions inventories of PM2.5 from cooking sources and
      biomass burning are not yet available, observational data in urban areas suggest
      that cooking sources account for approximately 5-20% of total primary emissions
      (excluding dust), and biomass burning sources are highly dependent on region.
      Finally, relatively few observational data were available to assess the accuracy
      of emission estimates for stationary sources. Overall, the uncertainties in
      primary emissions for PM2.s are substantial. Similar uncertainties exist for
      ammonia emissions. Because of these uncertainties, the design of PM2.5 control
      strategies should be based on inventories that have been refined by a combination
      of bottom-up and top-down methods.

PMID- 18318345
TI  - Tuareg ethnoveterinary treatments of camel diseases in Agadez area (Niger).
AB  - For generations, nomadic herders have been learning to manage herd health,
      particularly in dromedaries because of their great value. Owing to the
      unavailability of veterinary services, camel herders in remote areas have been
      developing their own pharmacopoeia and veterinary techniques. The bleeding of
      sick animals is a common treatment, as Tuareg herders believe that 'tainted
      blood' (izni) is the cause of many conditions. Several surgical techniques are
      also used, such as excision of calcified sublingual cord. The remedies mentioned
      in this survey are derived from Maerua crassifolia, Boscia senegalensis, Acacia
      raddiana, Cucumis prophetarum, Calotropis procera, Ricinus communis, Citrullus
      colocynthis, green tea, millet, tobacco and onions. Artificial elements are also
      used for treatment of animals: Powders collected from batteries, various haircare
      or skincare creams, crushed glass, insecticides or motor oil belong to their
      pharmacopoeia. This broadmindedness allows the introduction of modern veterinary
      medicine. Factors such as the lack of real production objectives constitute
      limits to this progress, however.

PMID- 18318346
TI  - Concurrent infection with bovine leukaemia virus and Theileria annulata in a
      Friesian calf.
AB  - Concurrent infection with bovine leukaemia virus (BLV) and Theileria annulata was
      diagnosed in a Friesian calf about 6 months of age at a dairy farm at the Qassim
      region of central Saudi Arabia. The disease ended fatally with signs of liver and
      heart failure. There was anorexia, pyrexia, anaemia, generalized oedema and
      jaundice. Haematology showed low RBC counts, PCV percentage and haemoglobin
      concentration and WBC counts. Lymphocyte differential was high. Examination of
      blood smears stained with Giemsa's stain showed the presence of piroplasms in red
      blood cells. Autopsy showed enlarged lymph nodes and lymphosarcoma lesions in the
      omentum and the heart. There was hydroperitoneum, hydropericardium and
      hydrothorax. The liver was pale yellow and friable. Impression smears from sliced
      lymph nodes and stained with Giemsa's stain showed presence of Koch's blue bodies
      in lymphoblasts. Histopathological examination revealed fatty degeneration of
      hepatocytes and pleomorphic lymphoblasts and giant cells in lymph nodes.
      Lymphoblasts infiltrated the omentum and heart tissues. Amyloid was found around
      blood vessels in the liver, kidneys and lymph nodes. BVL infection was diagnosed
      by demonstrating antibodies against the virus in serum using agar gel
      immunodiffusion and was confirmed with ELISA.

PMID- 18318347
TI  - Seasonal pattern of bovine amphistomosis in traditionally reared cattle in the
      Kafue and Zambezi catchment areas of Zambia.
AB  - Seasonality of bovine amphistomosis in the Southern province of Zambia was
      established after examining 268 faecal samples from cattle presented for
      slaughter at Turnpike slaughter slab, Mazabuka. Amphistomosis was found present
      throughout the year but the highest abundance rate was found during the post
      rainy season (47.8%) and the lowest during the cold dry season (24.8%). In the
      rainy and post-rainy seasons, higher mean egg counts and cattle found positive
      were recorded than in any other season. The distribution of amphistome eggs was
      significantly different (p < 0.001) among the four seasons, with the rainy season
      having higher median egg counts than others. There were no significant
      differences in abundance rates between sexes or between ages of cattle. A similar
      seasonality to that of fasciolosis exists and may help in strategic management of
      Fasciola and amphistomes.

PMID- 18318348
TI  - Local chicken production system in Malawi: household flock structure, dynamics,
      management and health.
AB  - Household flocks of scavenging chickens were monitored from August 2002 to August
      2003 in 27 villages in Lilongwe, Malawi. The objective was to evaluate the local
      chicken production system by investigating flock structure, utilization,
      management and constraints. Farmers and researchers jointly obtained data on
      household flocks. Mean flock size was 12.9, with a range of 1-61 chickens. The
      flock dynamics of chickens over 8 weeks old constituted 91% migrating out of
      flocks and 9% into the flocks. Primary functions based on flock dynamics were, in
      order of importance, household consumption, participation in socio-cultural
      ceremonies, selling, exchanging breeding stock and gifts. Of the flock exits,
      43.9% were due to losses from diseases, predation and theft. Most flocks (85%)
      were housed in human dwelling units. Scavenging was the main source of feed. The
      majority (77.6%) of farmers supplemented their chickens erratically with energy
      rich feeds, mostly maize bran. Most supplementation took place during the cold
      dry season. Village chicken production offers diverse functional outputs but
      faces animal health (diseases, parasites, predation) and management (feeding)
      constraints, which require an integrated intervention approach at community and
      household level.

PMID- 18318349
TI  - Indigenous Muscovy ducks in Congo-Brazzaville. 1. A survey of indigenous Muscovy
      duck management in households in Dolisie City.
AB  - A cross-sectional study by means of a questionnaire with open-ended questions and
      multiple-choice questions was used to collect data on the profile of duck
      keepers, husbandry practices, and performances, opportunities and constraints of
      Muscovy duck breeding in households (n = 88) in Dolisie city (Congo-Brazzaville).
      The study confirmed the common observations on traditional poultry keeping such
      as scavenging during the day and housing overnight. The flock size (7.7 +/- 3
      ducks per unit) showed no specialization of husbandry (100% of surveyed flocks
      were kept for simultaneous production of ducklings, meat and eggs) and a high
      drake-to-duck ratio (1:3). The hatchability was close to 80.5% +/- 13%, whereas
      the average number of eggs was 13.2 +/- 5 per clutch. In addition, a high
      mortality (80%) was observed in ducklings, which was due to poor feeding, lack of
      veterinary care and housing conditions. Eggs and live ducks were sold by duck
      farmers in response to the family needs rather than market price. The three most
      important findings were as follows: (1) duck keepers were mainly men (80% versus
      20% of women); (2) there was no evidence of taboo; and (3) the duck as an exotic
      bird was not proscribed by cultural beliefs, and therefore development of the
      Muscovy duck in Congo Brazzaville should be unhindered.

PMID- 18318350
TI  - Indigenous Muscovy ducks in Congo Brazzaville. 2. Preliminary observations on
      indigenous Muscovy ducks reared under moderate inputs in Congolese conditions.
AB  - To evaluate the potential of the native Muscovy ducks in Congo, a trial was
      conducted with closed housing, commercial feeding and veterinary care. The
      characterization included reproductive performance, daily weight gain, live body
      weight, feed conversion ratio, body live weight productivity, and meat
      productivity. The experimental genetic stock was bred under natural mating and
      natural incubation. The number of eggs recorded per female and per clutch was
      14.6 +/- 3 eggs with 2 clutches per year. The average (+/-SD) hatchability was
      75% +/- 3% and the average egg weight was 72 +/- 8 g. The sexual dimorphism for
      body weight appeared after 3 weeks (p < 0.05). The maximum daily weight gain in
      males reached 55 +/- 8 g/day and occurred at 5 weeks, whereas in females it
      occurred at 4 weeks and reached 35 +/- 5 g/day. The carcass yield was 70% +/- 5%
      and 51 +/- 8% in males and females, respectively. The meat productivity was 26.7
      and 11.5 kg/m2 per year in males and females, respectively. From these findings,
      it can be concluded that the incubation by mother duck is preferred in the small
      farming duck and that males should be raised for meat and females for egg
      production. Further studies including local poultry-related issues are needed to
      optimize the performance of the native Muscovy duck in Congo-Brazzaville.

PMID- 18318351
TI  - Ovarian activity, transuterine embryo migration and prenatal losses in Ethiopian
      highland ewes.
AB  - A study was conducted on 1442 Ethiopian highland ewes to determine the
      seasonality of ovarian activity, intrauterine embryo migration and prenatal
      reproductive wastage. Assessment of ovarian follicular activity revealed that a
      higher (p < 0.01) proportion of ewes ovulated in the dry season than in the heavy
      and light rainy seasons. However, there was a tendency (p = 0.057) of decline in
      the mean number of ovulations per ewes during the light rains. The mean diameter
      of the largest follicle on the ipsilateral ovary was higher (p < 0.01) in both
      ewes with single and those with twin corpora lutea (CL) than on the contralateral
      ovary; and, compared to ewes with single CL, it was higher (p < 0.05) in those
      with twin CL. The right ovary was more active (p < 0.001) only in single
      ovulating ewes. Similarly, a higher (p < 0.001) proportion of ewes were pregnant
      in the right horn. Embryos migrated to the opposite horn in single-, twin- and
      triple-ovulating ewes. There was a higher (p < 0.001) tendency for the left-to
      right migration than the opposite. There was significant (p < 0.01) association
      between embryo loss and site and number of ovulations. Embryo loss was higher (p
      < 0.01) in ewes with twin ovulations on the right ovary. It is very likely that
      these results indicate a better chance of embryo survival in the right uterine
      horn.

PMID- 18318352
TI  - Birth weight, birth type and pre-weaning survivability of West African Dwarf
      goats raised in the Dangme West District of the Greater Accra Region of Ghana.
AB  - A study was conducted on 441 West African Dwarf goat (WADG) kids born from
      September 1999 to August 2002 at three locations in the Dangme West District of
      the Greater Accra Region in Ghana to determine the effect of environmental
      factors on birth weight, birth type and pre-weaning survivability. The overall
      mean birth weight was 1.32 +/- 0.01 kg. Birth weights were similar (p > 0.05)
      between single births (1.43 +/- 0.04 kg) and twins (1.34 +/- 0.03 kg), but
      singles were significantly heavier (p < 0.05) than triplets (1.24 +/- 0.05 kg).
      Kids born in the major wet season recorded the best mean birth weight (1.37 +/-
      0.04 kg). Sex, parity of does, and year of birth of kids had no significant (p >
      0.05) effect on birth weight. Mean litter size was 1.93 +/- 0.03. Does that
      kidded in the dry season had a significantly (p < 0.05) higher litter size (2.05
      +/- 0.06) than those that kidded in the minor wet season (1.80 +/- 0.10). Litter
      size of first-parity kids was significantly smaller (p < 0.05) than in subsequent
      parities. Litter size dropped significantly (p < 0.05) from year 2 (2.03 +/-
      0.07) to year 3 (1.83 +/- 0.07). Pre-weaning survivability was 79.1% and season
      of kidding had a significant (p < 0.05) effect on survivability. Survivability of
      quadruplets (61.8%) was significantly (p < 0.05) lower than in the other birth
      types.

PMID- 18318353
TI  - Effect of season and supplementation on percentage live sperm and sperm
      abnormalities in Horro (Zebu) bulls in sub-humid environment in Ethiopia.
AB  - A total of 32 Horro (Bos indicus) bulls, with an average initial body weight and
      age of approximately 211 kg and 6 years were evaluated. The bulls were divided
      into two treatment groups. One group was given a supplementary concentrate at a
      rate of 1.5 kg/day and the second group served as the control and received no
      supplementation. The observation period lasted for 50 weeks. Semen was collected
      every two weeks by mean of electrical stimulation with the aid of an electro
      ejaculator. The percentage of abnormal sperm (total abnormalities, head, midpiece
      and tail) remained lower in the supplemented group than in the non-supplemented
      group. The percentage of live sperm tended to be higher in the supplemented group
      throughout the 50-week trial period. Until week 17 of the trial there were no
      significant differences; however, starting at week 18 there were significant
      differences between the two treatment groups except for week 26. Thereafter,
      significant differences were recorded until week 38; from week 40 no significant
      differences were observed between the two groups in respect of percentage of live
      sperm (except for week 48). Season (week) during which the semen samples were
      collected had no significant effect on the percentage of abnormal sperm in both
      treatment groups (supplemented and non-supplemented). At the start of the trial
      the nutritionally supplemented group had a higher occurrence of sperm
      abnormalities (11.4% +/- 1.1%) compared to 8.3% +/- 1.3% in the control group.
      Thereafter, sperm abnormalities declined rapidly in the supplemented group
      (except for week 50). The sperm abnormalities for the non-supplemented group
      showed a tendency to increase during the entire observation period.

PMID- 18318354
TI  - Impending staffing shortage... Again?

PMID- 18318355
TI  - No, I'm sorry, you don't get paid for that either.

PMID- 18318356
TI  - Understanding the revenue cycle: coordinated billing process key to radiology
      success.
AB  - *An integrated approach across all involved departments is the key to revenue
      cycle success. *Accurate, complete, and timely data drives the revenue cycle. *Up
      to-date and accurate coding and charge capture will help ensure that the
      institution is reimbursed correctly.

PMID- 18318357
TI  - DICOM questions, answered.
AB  - *Connectivity issues due to the DICOM standard are still occurring even though it
      is a mature standard. This is due to a lack of training, a professional
      certification effort that is still in its infancy, and user errors. *DICOM
      modality worklists, sometimes not able to filter out exams that should be
      performed at a specific modality, are one of the troublespots. *New modality
      types, such as the panorex dental systems, create connectivity issues because
      many PACS systems do not yet have support to properly archive these images.

PMID- 18318358
TI  - Leadership challenges of a multigenerational workforce.
AB  - *Throughout history, the ability of a society to survive has been predicated on
      that society's willingness to adapt to cultural changes between generations and
      its effectiveness in passing knowledge and experience from one generation to
      another. *For current and future leaders in healthcare, an understanding of this
      principle is critical with the advent of a 4 generation workforce and the pending
      retirement of over 40% of the current workforce over the next decade. *Knowledge
      of the characteristics of each generation and the variation between generations
      is only a beginning. The challenges are to lead--to navigate the conflicts
      between the values and priorities of the different composites of the workforce-
      and to orchestrate the transfer of knowledge and expertise from one generation of
      workers to another.

PMID- 18318359
TI  - Employee incentives in the healthcare industry.
AB  - *Employee incentives are an important part of a radiology department's ability to
      attract and maintain employees. For incentive programs to be successful,
      radiology managers must diligently look for the incentives that motivate each
      particular employee. *The types of incentives being used frequently in the field
      of healthcare vary between technical, managerial, and executive positions. The
      process of identifying the right employee incentive for each group of individuals
      may be challenging, but if the result is a more productive and satisfied group of
      employees, the process is worth the effort.

PMID- 18318360
TI  - Do you have differential advantage?

PMID- 18318361
TI  - Disaster drill.

PMID- 18318362
TI  - The hazard in hookah smoke. Water pipes seem safer than cigarettes--but may be
      worse.

PMID- 18318363
TI  - A cancer gene for men, too.

PMID- 18318364
TI  - My bills are headed lower.

PMID- 18318365
TI  - Diet today, don't tomorrow. Fasting and skipping meals might actually be good for
      you.

PMID- 18318366
TI  - Closer to vanquishing the virus.

PMID- 18318367
TI  - Back to the drawing board. Hospitals, insurer support not enough to save
      California's universal coverage plan; lack of physician backing hurt chances.
AB  - A defeat in California for Gov. Arnold Schwarzenegger's comprehensive healthcare
      reform plan was not only a blow to advocates of the initiative but also could be
      a setback for other states that were hoping to follow in the Golden State's
      footsteps. Lloyd Dean, left, president and CEO of Catholic Healthcare West, said
      that he is "concerned this lack of progress will result in further deterioration
      of California's healthcare system".

PMID- 18318368
TI  - Stay the course. Doubtful any big changes coming.

PMID- 18318369
TI  - FDA's device inspection lacking. Two reports point to technology, staffing as key
      culprits.

PMID- 18318370
TI  - Health workers saying, 'union, yes'. New federal government statistics show 10.4%
      bump in '07 membership.

PMID- 18318371
TI  - Georgia CONtroversy. State divided on surgical specialist ASC issue.

PMID- 18318372
TI  - Is this really their legacy? Shelton's new company has handful of board members
      with potential conflicts.

PMID- 18318373
TI  - Proactive medicine. The benefits of an EMR in locations without one.

PMID- 18318374
TI  - Integrating efficiency. Verispan's annual ranking of the top integrated health
      networks shows improved operating margins along with expanded services.

PMID- 18318375
TI  - By the numbers. Largest healthcare law firms ranked by total membership in the
      American Health Lawyers Association.

PMID- 18318376
TI  - Will Virginia turn on the crop that saved it? With the polls to back it, the
      governor pushes for a smoking ban in the shadow of Philip Morris.

PMID- 18318377
TI  - Keeping your brain fit. There's plenty you can do to slow the effects of aging.
      Here's how to keep your thinking and memory sharp.

PMID- 18318378
TI  - Stitching together a new life. Here's a yarn: a former nurse finds focus in a
      knitting business.

PMID- 18318379
TI  - Covered but far from safe. Individual health plans often fall short when needed
      most.

PMID- 18318380
TI  - Goodbye, pain in the neck.

PMID- 18318381
TI  - Campus health's hidden costs. Students often face unexpected--and unnecessary-
      fees.

PMID- 18318382
TI  - After Triad, a chain is born. Former Triad leaders form Legacy Hospital Partners,
      aiming to make joint ventures with not-for-profits looking for capital.
AB  - Some former Triad executives have gotten together and formed a chain called
      Legacy Hospital Partners. Dan Moen, left, Triad's former executive vice
      president, is Legacy's president and chief executive officer. He and Triad's
      former CEO, Denny Shelton, say the company will stay out of markets where Triad
      operated a hospital until a noncompete clause expires in 2010.

PMID- 18318383
TI  - Dual duties. Not-for-profit execs land on board.

PMID- 18318384
TI  - HHS' new year's resolutions. Leavitt's priorities: fix SGR, increase health IT).

PMID- 18318385
TI  - Democratic lawmakers create task force. Trio of former healthcare professionals
      ready to push IT, disease-management bills.

PMID- 18318386
TI  - Einstein CEO joins board. Appointment ties exec to two GPOs.

PMID- 18318387
TI  - As U.S. toots its own corn...living a healthy lifestyle winds up taking a
      supersized back seat.

PMID- 18318388
TI  - HSAs: a risky strategy. Changes needed to avoid avalanche of medical debt.

PMID- 18318389
TI  - M&A trend: no big deal. Tight credit could make it tougher to finance large for
      profit acquisitions like those that made headlines the past two years.

PMID- 18318390
TI  - By the numbers. Largest healthcare services mergers/acquisitions announced in
      2007. U.S. deals ranked by deal's price.

PMID- 18318391
TI  - Taking a hard look. Insurers increase scrutiny of imaging providers.

PMID- 18318392
TI  - [Detection of viable metabolically active yeast cells using a colorimetric
      assay].
AB  - The increasing concern of yeasts able to form biofilm brings about the need for
      susceptibility testing of both planktonic and biofilm cells. Detection of
      viability or metabolic activity of yeast cells after exposure to antimicrobials
      plays a key role in the assessment of susceptibility testing results.
      Colorimetric assays based on the color change of the medium in the presence of
      metabolically active cells proved suitable for this purpose. In this study, the
      usability of a colorimetric assay with the resazurin redox indicator for
      monitoring the effect of yeast inoculum density on the reduction rate was tested.
      As correlation between the color change rate and inoculum density was observed,
      approximate quantification of viable cells was possible. The assay would be of
      relevance to antifungal susceptibility testing in both planktonic and biofilm
      yeasts.

PMID- 18318393
TI  - [Seroprevalence of Toxoplasma gondii among pregnant women in Slovakia].
AB  - Toxoplasmosis is caused by a protozoan parasite, Toxoplasma gondii. Primary
      infection with Toxoplasma gondii in pregnant women can lead to adverse outcomes.
      Since initially asymptomatic, toxoplasmosis is difficult to diagnose. The aims of
      this study were to determine the seroprevalence of toxoplasmosis in pregnant
      women in Slovakia and to identify possible risk factors. As many as 145 (22.1%)
      of 656 pregnant women screened for T. gondii were seropositive. The prevalence of
      toxoplasmosis significantly increases with age and the highest seropositivity
      rate (35.4 %) was found in the age group of 35-44 years. A significantly higher
      seropositivity rate was observed in women living in the surroundings of
      Bratislava (63.5%) as compared to Bratislava (36.6%, p < 0.001; OR = 0.53, 95% CI
      = 0.36-0.79) Among the epidemiological factors, contact with soil appeared
      statistically significant (35.3%, p = 0.014; OR = 1.67, 95% CI = 1.09-2.56).
      Fatigue (32.1%, p = 0.026; OR = 1.84, 95% CI = 1.03-3.27), miscarriages (44.1%, p
      = 0.002; OR = 2.22, 95% CI=1.3-3.8) and toxoplasmosis in the family (10.7%, p =
      0.002) were most commonly reported in history of the study subjects.

PMID- 18318394
TI  - [Invasive pneumococcal disease in the Czech Republic in 2000-2006].
AB  - STUDY OBJECTIVE: To assess the incidence of invasive pneumococcal disease and
      coverage of the causative serotypes by pneumococcal vaccines in the Czech
      Republic. METHODS: The incidence and fatality rates of reported cases of
      pneumococcal meningitis (EPIDAT) in 1997-2006 are analyzed. In addition, the data
      of the National Reference Laboratory for Streptococci and Enterococci from 2000
      2006 are presented. The incidence of invasive pneumococcal disease was calculated
      for the catchment population of the collaborating laboratories. Pneumococcal
      typing was performed in the National Reference Laboratory. The percentages of
      pneumococcal serotypes isolated from invasive disease in 2000-2006 and included
      in the pneumococcal vaccines were calculated. RESULTS: The incidence of invasive
      pneumococcal disease ranged from 2.30 to 4.28/100000 population. The age-specific
      incidence of invasive pneumococcal disease in 2000-2006 was the highest in the
      lowest age groups 0-11 months (15.75/100000) and 1-4 years (8.22/100000),
      followed by the age group of 65 years and older (7.3/100000). The total fatality
      rate of pneumococcal meningitis in 1997-2006 was 13.7%. The highest age-specific
      fatality rate was recorded in 65-year olds and over (24%). In the age group 0-11
      months, the coverage of pneumococcal serotypes is 66% by the 7-valent conjugate
      vaccine, 76% by the 10-valent conjugate vaccine and 82% by thel3-valent conjugate
      vaccine. In the age group 1-4 years, the respective rates are 65.1%, 76.4% and
      85.8%. The coverage of serotypes by conjugate vaccines is higher in the youngest
      age groups (0-11 months and 1-4 years) compared to adults (40-64 years and 65
      years and older). CONCLUSION: Based on laboratory data, the incidence of invasive
      pneumococcal disease in the Czech Republic in 2000-2006 is comparable with the
      rates reported in other European countries. The highest incidence rates were
      observed in the youngest age groups. The distribution of serotypes causing
      invasive pneumococcal disease differs between children and adults. The coverage
      of serotypes by conjugate pneumococcal vaccines is higher in children (66-65%)
      compared to adults (34-65%). It is desirable to launch a nationwide programme of
      surveillance of invasive pneumococcal disease. Furthermore, it is recommended
      that a conjugate pneumococcal vaccine should be included in the children's
      immunization schedule.

PMID- 18318395
TI  - [Multidisciplinary approach to the management of vulvovaginal discomfort].
AB  - Vulvovaginal discomfort is generally the most common reason for visiting a
      gynaecological clinic. The acute complaints are, in most cases, solved by a
      gynaecologist himself and the decision procedure is based on possibilities
      arising from outpatient examination. If need be, the evaluation of wet
      preparation should be carried out. In many cases we have been confronted with
      discrepant diagnosis where severe difficulties are not accompanied by relevant
      development of inflammatory changes and thus the diagnosis gives us an impression
      of quandary. In this case microbiological examination is the logic solution. With
      regard to changing living conditions we can expect in the future, that clinical
      symptoms of vulvovaginitis will not be entirely clear. The overview article
      points out the possibilities, which a gynecologist is able to use within
      differential diagnosis in the outpatient department. It also emphasis the
      necessity of interdisciplinary co-operation, particularly in patients with
      chronic difficulties where erudite evaluation of fixed preparation and culture
      examination are beneficial.

PMID- 18318396
TI  - [An outbreak of type A viral hepatitis in 1979. Memories of an old
      epidemiologist. Part one].

PMID- 18318397
TI  - [Karel Raska--An outstanding personality in the fight against microbes].

PMID- 18318398
TI  - Career change. Back to the NHS.

PMID- 18318399
TI  - Young people. Out with the old.

PMID- 18318400
TI  - Service redesign. Whose job is it anyway?

PMID- 18318401
TI  - Public health. Where work is good for you.

PMID- 18318402
TI  - Nursing. A reality check for diversity.

PMID- 18318403
TI  - Urgent care. Steady progress, urgent need.

PMID- 18318404
TI  - Public involvement. Use strategy to buck the trends.

PMID- 18318405
TI  - Time-based and event-based prospective memory across adulthood: underlying
      mechanisms and differential costs on the ongoing task.
AB  - The authors investigated the phenomenon that performance in an ongoing task
      declines when individuals must carry out a prospective memory (PM) task. This
      effect is referred to as the PM interference effect. The authors examined whether
      the PM interference effect differs between event-based and time-based PM tasks
      and whether it is increased among the elderly. The authors also investigated
      adult age differences in PM performance and the potential underlying mechanisms
      of the age deficits in PM. They found that the PM interference effect was greater
      in event-based than in time-based tasks. However, aging was not associated with
      an increase in PM interference effects. Age differences in PM performance were
      more exaggerated in time-based than event-based PM, but they were not mediated by
      age differences in traditional cognitive ability measures. In time-based PM, age
      showed a unique adverse effect even after controlling for the ability to
      externally monitor the time, leading to the possibility that aging disrupts time
      based PM because of deficits in internally processing the time.

PMID- 18318406
TI  - Biased lineup instructions and face identification from video images.
AB  - Previous eyewitness memory research has shown that biased lineup instructions
      reduce identification accuracy, primarily by increasing false-positive
      identifications in target-absent lineups. Because some attempts at identification
      do not rely on a witness's memory of the perpetrator but instead involve matching
      photos to images on surveillance video, the authors investigated the effects of
      biased instructions on identification accuracy in a matching task. In Experiment
      1, biased instructions did not affect the overall accuracy of participants who
      used video images as an identification aid, but nearly all correct decisions
      occurred with target-present photo spreads. Both biased and unbiased instructions
      resulted in high false-positive rates. In Experiment 2, which focused on video
      photo matching accuracy with target-absent photo spreads, unbiased instructions
      led to more correct responses (i.e., fewer false positives). These findings
      suggest that investigators should not relax precautions against biased
      instructions when people attempt to match photos to an unfamiliar person recorded
      on video.

PMID- 18318407
TI  - Prepartum and postpartum open-field behavior and maternal responsiveness in mice
      bidirectionally selected for open-field thigmotaxis.
AB  - The authors examined pre- and postpartum open-field (OF) behavior and maternal
      responsiveness in mice that they bidirectionally selected for OF thigmotaxis. The
      authors tested 40 female mice under 3 conditions: prepartum OF, postpartum OF,
      and a pup retrieval test. In both OF conditions, the high OF thigmotaxis (HOFT)
      mice were more thigmotactic but explored and reared less than the low OF
      thigmotaxis (LOFT) mice, indicating that the HOFT mice were more emotional. In
      the postpartum condition, the HOFT mothers also defecated more and ambulated less
      than the LOFT mothers. The increase in grooming after parturition was more
      conspicuous among the LOFT mothers than among the HOFT mothers. The LOFT mothers
      were also more attracted to their pups in the OF, but the retrieval test did not
      show any substantial line differences. The results suggested that the line
      difference in emotionality was more pronounced during lactation than during
      pregnancy, although parturition exerted no effect on thigmotaxis.

PMID- 18318408
TI  - Dwarf and golden hamsters' differing responses to conspecific signals for food.
AB  - The author presented dwarf hamsters (Phodopus campbelli) and golden hamsters
      (Mesocricetus auratus) with conspecific and inanimate signals for food. Both
      species approached a cardboard stimulus that predicted food. The dwarf hamsters
      engaged in high levels of social contact directed toward a conspecific
      conditioned stimulus for food, but the golden hamsters did not. The author also
      presented dwarf hamsters with a conspecific signal that did not indicate food,
      and the levels of social behaviors that they directed toward it were
      significantly lower. These results suggest the presence of a social component in
      the dwarf hamster feeding system and are consistent with previous findings that
      the social transmission of food preferences occurs more readily in dwarf hamsters
      than in golden hamsters.

PMID- 18318409
TI  - Two routes for activation in the priming of categorical coordinates.
AB  - The authors operationalized category priming as participants' recognition
      facilitation of nonstudied, low semantically similar exemplars by studied
      exemplars in a category. The existing literature either does not examine the
      effect of studied exemplars on nonstudied exemplars in a category or fails to
      show an appreciable amount of category priming. In 2 experiments, the authors
      demonstrated a unique process to account for the category priming effect and
      distinguish it from the semantic priming effect, facilitation of semantically
      similar exemplars, in the context of a category. In Experiment 1A, the authors
      used a multidimensional scaling technique to examine participants' internal
      structure of different categories. In Experiment 1B, the authors used a lexical
      decision task that used these internal structures to show that semantic encoding
      of category exemplars causes activation of existing category knowledge in memory.
      Consequently, participants easily recognized nonstudied, low semantically similar
      exemplars in a category. However, recognition facilitation between high
      semantically similar exemplars did not require category knowledge activation.

PMID- 18318410
TI  - Influence of recall procedures on the modality effect with numbers and enumerated
      stimuli.
AB  - Experiment 1 extended J. S. Nairne and W. L. McNabb's (1985) counting procedure
      for presenting numerical stimuli to examine the modality effect. The present
      authors presented participants with dots and beeps and instructed participants to
      count the items to derive to-be-remembered numbers. In addition, the authors
      presented numbers as visual and auditory symbols, and participants recalled items
      by using free-serial written recall. Experiment 1 demonstrated primacy effects,
      recency effects, and modality effects for visual and auditory symbols and for
      counts of dots and beeps. Experiment 2 replicated the procedure in Experiment 1
      using strict-serial written recall instead of free-serial written recall. The
      authors demonstrated primacy and recency effects across all 4 presentation
      conditions and found a modality effect for numbers that the authors presented as
      symbols. However, the authors found no modality effect when they presented
      numbers as counts of beeps and dots. The authors discuss the implications of the
      results in terms of methods for testing modality effects.

PMID- 18318411
TI  - Comparing dependent correlations.
AB  - In a recent article in The Journal of General Psychology, J. B. Hittner, K. May,
      and N. C. Silver (2003) described their investigation of several methods for
      comparing dependent correlations and found that all can be unsatisfactory, in
      terms of Type I errors, even with a sample size of 300. More precisely, when
      researchers test at the .05 level, the actual Type I error probability can exceed
      .10. The authors of this article extended J. B. Hittner et al.'s research by
      considering a variety of alternative methods. They found 3 that avoid inflating
      the Type I error rate above the nominal level. However, a Monte Carlo simulation
      demonstrated that when the underlying distribution of scores violated the
      assumption of normality, 2 of these methods had relatively low power and had
      actual Type I error rates well below the nominal level. The authors report
      comparisons with E. J. Williams' (1959) method.

PMID- 18318412
TI  - The photoparoxysmal response: the probable cause of attacks during video games.
AB  - Photic stimulation is part of a typical EEG in most countries, especially to
      check on the photoparoxysmal response (PPR). Interest in this response was
      enhanced in 1997 when hundreds of Japanese children had attacks while viewing a
      TV cartoon called "Pokemon." The overall prevalence of the PPR among patients
      requiring an EEG is approximately 0.8%, but 1.7% in children and 8.87% in
      patients with epilepsy, more often in Caucasians and females. Autosomal dominant
      inheritance is indicated, and this response is seen especially at the wavelength
      of 700 nm or at the flicker frequency of 15-18 Hz. The PPR extending beyond the
      stimulus carries no increased risk of seizures. Prognosis is generally good,
      especially after 20 years of age. Attention to PPR has been increased with the
      advent of video games, and the evoked seizures from these games are likely a
      manifestation of photosensitive epilepsy. Drug therapy has emphasized valproic
      acid, but Levetiracetam has also been successful in eliminating the PPR.

PMID- 18318413
TI  - Vertebrobasilar artery insufficiency and electroencephalogram.
AB  - This is a renewed diagnostic approach to vertebrobasilar artery insufficiency
      (VBI)--a condition which stood in the focus of this author's interest several
      decades ago. The time for a revisitation has come. The EEG findings consist
      mainly of generally reduced voltage output and enhanced photic driving response.
      There is also some theta activity over anterior temporal and midtemporal region,
      but this finding is common in the early stage of all cerebrovascular disorders.
      Dysfunction of the pontine portion of the ascending reticular formation might be
      the cause of the lowered voltage output. The enhanced photic driving might be due
      to very light hypoxia of the visual cortex.

PMID- 18318414
TI  - EEG infraslow activity in absence and partial seizures.
AB  - It is currently assumed that for recording of infraslow activity (ISA) DC-coupled
      amplifiers are required. This report will demonstrate that this may not be the
      case and presents some data about its potential clinical usefulness. Archived
      EEGs of 29 seizures from 6 children with absence attacks, accompanied by 3 Hz
      classical spike-wave discharges (SW), were compared with 20 partial seizures from
      10 adult patients. The data from the children were acquired on a Bio-logic
      system, those from the adults on a Grass-Telefactor instrument. In the children
      the original 30-minute routine EEG was used while in the adults stored
      videomonitored data were excerpted to provide 20-minute segments which included
      the preictal, ictal and postictal state. All data were analyzed with the BESA
      software package. The seizures were evaluated separately on conventional filter
      settings, full band of 0.01-to the upper limit of the instrument, and 0.01-0.1 Hz
      (infraslow activity, ISA). Filter settings of 0.01-0.1 Hz provided a better
      assessment of ISA than when the full band was evaluated. Absence seizures showed
      bilateral essentially synchronous ISA with a negative positive sequence in the
      frontal areas and opposite polarity in the posterior head regions. In partial
      seizures when seizure onset was clearly lateralizeable from conventional
      frequency settings ISA corresponded to that hemisphere, but the electrode
      position could be displaced to a neighboring one from the one which was maximally
      involved on conventional settings. Topographic analysis showed two types of ISA:
      one with focal spread only and the other where there was in addition an element
      of synchrony especially in the frontal areas. It is concluded that ISA can be
      recovered from conventional EEG recordings and may be helpful not only in
      determining the area(s) of seizure onset but can also differentiate truly focal
      seizures from those where an additional generalized seizure tendency is present.
      This is likely to be important when epilepsy surgery is performed in absence of a
      demonstrable structural lesion.

PMID- 18318415
TI  - Ictal scalp EEG findings in patients with mesial temporal lobe epilepsy.
AB  - The syndrome of mesial temporal lobe epilepsy (MTLE) is a well-defined clinical
      entity that responds to surgical treatment in a considerable number of patients.
      Although it has been subjected to intensive clinical research, few investigators
      have published the ictal scalp EEG findings and looked for specific features that
      might predict postoperative outcome. This study was designed to examine ictal
      scalp EEG characteristics in detail, in a group of patients with pathologically
      confirmed hippocampal sclerosis (HS). Patients who underwent long-term video-EEG
      monitoring at our center during a 3-year period and were diagnosed to have MTLE
      and pathologically proven HS were included in this retrospective study. All ictal
      scalp EEGs were investigated in a common reference montage, paying attention to
      the localization, morphology and frequency of ictal discharges that were accepted
      to represent a specific phase if the findings were sustained for at least 3
      seconds. Any significant change in localization, morphology or frequency of
      discharges was said to represent a different phase. The ictal EEG patterns in
      different phases were later compared among seizures of different patients. In
      addition, the ictal EEG characteristics of the patients in Group I (Engel's
      classification) were compared with the ictal EEG findings in patients who were
      included in another group. All the patients have been followed for more than 5
      years. Seventy-one ictal EEGs were investigated in 25 adult patients (11 M, 14
      F). Onset patterns were lateralized in 81.7% and localized in 76% of the
      seizures. Thirteen different patterns of onset were detected, the most common of
      which was the cessation of interictal discharges (35.2%). The most common ictal
      pattern following the initial changes was ipsilateral temporal rhythmic theta
      delta activity (85.2%) that occurred on the average 13.4 seconds after onset.
      Nonlocalized/lateralized seizure onset of all the seizures or bilateral
      independent onset was present in 75% of the patients in Groups II-III, whereas
      this ratio was 14.3% in the patients in Group I (p=0.031). In conclusion, ictal
      scalp EEG in MTLE allows correct lateralization and localization in most of the
      seizures. Onset patterns may vary considerably; however, a later significant
      pattern consisting of rhythmic ipsilateral temporal build-up develops in the
      majority of seizures. Some ictal EEG characteristics may be related to post
      operative outcome.

PMID- 18318416
TI  - Midline spikes.
AB  - Midline spikes are characterized by spike foci recorded at Cz, Fz, or Pz with
      amplitude ranging from 20 to 350 microvolts. Out of 7,929 EEGs performed at the
      Neurodiagnostics Laboratory, Kaiser Permanente Medical Center, Anaheim,
      California, between 1996 and 2006, 17 EEGs (0.21%) were identified as having
      interictal midline spikes with or without other epileptiform discharges. Eight
      EEGs showed midline spikes at Cz, 2 at Fz, 2 at Cz and Fz, 1 at Cz and C3, 1 at
      Cz, C3, and P3, 1 at Cz and F8, 1 at Cz and T4, and 1 at Cz with 2 Hz generalized
      spike and slow wave complex. Midline spikes were recorded in 10 males and 7
      females. The age ranged from 4 days to 38-years-old with a mean age of 10.8
      years. Twelve patients (70.6%) were children. Twelve patients (70.6%) had
      generalized tonic-clonic seizures and 5 had partial motor seizures. Of the 17
      patients, 14 had no known causes, 1 had an agenesis of corpus callosum, 1 had a
      left frontal arteriovenous malformation, and 1 had a left frontal area stroke. We
      postulate that the mechanism for the genesis of midline spikes may be
      heterogeneous. Midline spikes may be triggered by thalamocortical network in a
      generalized tonic-clonic seizure, or may originate in the parasagittal cortex in
      a partial motor seizure.

PMID- 18318417
TI  - Focal EEG findings in juvenile absence syndrome and the effect of antiepileptic
      drugs.
AB  - The presence of focal EEG abnormalities in juvenile absence syndrome (JAS) may
      cause it to be misdiagnosed as focal epilepsy. The purpose of our study was to
      determine the presence of focal EEG abnormalities in patients with JAS and to
      ascertain whether some clinical features or antiepileptic drugs (AEDs) have an
      effect on focality. Serial EEGs of 52 consecutive patients with JAS were
      retrospectively analyzed. The patients were divided into two groups according to
      whether they were treated with valproic acid and/or lamotrigine (VA-LTG) or not
      during the times of these EEG recordings. The relationship between the presence
      of EEG focality and the use of AEDs in addition to other risk factors was
      examined. Two or three consecutive EEGs (total 100) of the 52 patients were
      evaluated. Among these, the rates of focal EEG abnormalities were 18%, 36%, and
      25% during the follow-up EEGs without AEDs (5/27) and first (16/45) and second
      EEGs (7/28) with AEDs, respectively. The last two EEGs showed a tendency towards
      a higher proportion of EEG focality in patients who received other AEDs (47%-45%)
      compared with those that received VA-LTG (13%-12%). The proportion of JAS
      patients with focal EEG findings in serial EEGs tended to decrease with an
      increasing rate of VA-LTG use. As a hypothetical explanation, changes in EEG
      focality may reflect the effect of AEDs other than VA and/or LTG, in addition to
      a developing hyperexcitable cortical area.

PMID- 18318418
TI  - Akinesia and the frontal lobe.
AB  - A report of severe akinetic episodes in patients with Parkinson disease (PD) has
      been the stimulus for the following discussion of akinesia and its variants.
      Severe persistent akinesia may occur in frontal lobe impairment. Therefore, it is
      likely that extension of the Parkinsonian dysfunction into the frontal lobe
      causes severe akinesia which should be separated from the very common
      Parkinsonian hypokinesia. Another very common clinical phenomenon of PD is sudden
      freezing. Hence the frontal lobe--hardly regarded as a region of special interest
      in the realm of PD--can be the cause of severe and dangerous complications of PD.
      The term "arrest reaction" or "motor arrest" denotes a similar freezing. It is
      recommended to restrict these terms to certain forms of frontal lobe epilepsy.
      This discussion of hypokinetic and akinetic states should also include catatonia:
      a form of schizophrenia with a special type of akinesia. Though without major
      neuropathological substratum, this condition can, in extremely rare cases, lead
      to severe hyperthermia and fatal outcome (presumably via hypothalamic
      dysfunction).

PMID- 18318419
TI  - Ictal/interictal EEG patterns and functional neuroimaging findings in subcortical
      band heterotopia: report of three cases and review of the literature.
AB  - Subcortical band heterotopia (SBH) is a rare, genetic disorder of neuronal
      migration, which is seen almost exclusively in females. Little is known about the
      functionality of the band heterotopia, in terms of both physiology and pathology,
      in this malformation. Patients are reported to have several different types of
      seizures, which are usually drug resistant. Interictal EEG findings are known to
      correlate with the type of seizures, however less is known about the ictal EEG
      patterns. We present 3 female patients who were investigated at our center with
      video-scalp EEG monitoring, interictal single photon emission computed tomography
      (SPECT), functional magnetic resonance (MR) imaging (fMRI) and MR spectroscopy
      (MRS) besides routine MR imaging. They had several different types of seizures,
      and one of them reported also having circling seizures that have not been
      reported previously in patients with SBH. Ictal EEG recordings were remarkable
      for their unusual patterns of propagation. The findings in structural and
      functional neuroradiological investigations are discussed in light of the
      literature.

PMID- 18318420
TI  - Event-related brain potentials in reading disabled children during an inverse
      serial digit detection task.
AB  - It has been reported that limitations in different components of working memory
      could underlie reading disabilities. In addition, reading-disabled (RD) children
      seem to perform worse when digit name processing is required. With the purpose to
      explore further these assumptions one inverse serial digit detection task was
      evaluated using event-related brain potentials in fifteen 8-year-old RD children
      and a control group (CG). CG obtained significantly more correct responses than
      RD, but had similar reaction times. The experimental task performance
      significantly correlated with the performance on reading tests. Difference event
      related potentials showed a voltage component peaking at 160 ms over
      frontocentral leads (P160d) that reached significantly higher amplitude in RD
      group, and was interpreted as an index of the amount of neural resources involved
      in visual working memory load. The amplitude of P160d significantly correlated
      with reading speed, the backward digit span and with the experimental task
      performance. Present results point out that highly demanding working memory tasks
      reveal behavioral and electrophysiological differences in RD children with
      respect to healthy controls.

PMID- 18318421
TI  - Failure to obtain value enhancement by within-trial contrast in simultaneous and
      successive discriminations.
AB  - The present research tested the generality of the "work ethic" effect described
      by Clement, Feltus, Kaiser, and Zentall (2000). In Experiment 1, we trained 10
      pigeons on a pair of either simultaneous or successive discriminations. One
      discrimination followed a high-effort requirement (20 pecks to the center key)
      and the other followed a low-effort requirement (1 peck). Contrary to Clement et
      al.'s results, we found that preferences between the S+ and S- stimuli in
      transfer tests depended on the event that initiated the trial: Pigeons preferred
      the stimulus from the baseline discrimination whose initiating event was most
      dissimilar from that preceding the test trial. Preferences were similar but less
      extreme in the successive condition. In Experiment 2, we investigated whether
      test preferences depended on the amount of training. A total of 12 pigeons were
      trained on a pair of simultaneous discriminations, except that test sessions were
      scheduled after every three baseline sessions. Preferences increased across test
      sessions but were similar to those in Experiment 1. Together with Vasconcelos,
      Urcuioli, and Lionello-DeNolf (2007a), our study represents a second failure to
      replicate Clement et al.'s work ethic effect. The finding that preference depends
      on the event that initiates the test trial suggests that choice probes may not
      provide unambiguous assessments of stimulus value.

PMID- 18318422
TI  - Deprivation level and choice in pigeons: a test of within-trial contrast.
AB  - Within-trial contrast has been proposed as a mechanism underlying preferences for
      stimuli that follow relatively more aversive events over stimuli that follow less
      aversive events. In this study, we manipulated deprivation level to test within
      trial contrast predictions. In Experiment 1, pigeons encountered two
      discriminative stimuli, one presented when they were deprived and the other when
      they were prefed. When later given a choice between the two stimuli, pigeons
      strongly preferred the stimulus encountered when deprived, independently of their
      deprivation level at test. In Experiment 2, pigeons learned two simultaneous
      discriminations, one when deprived and the other when prefed. Here, subsequent
      tests between the two S+ or the two S- stimuli revealed no consistent
      preferences. These contrasting findings suggest that differential aversiveness is
      necessary but not sufficient to induce preferences via within-trial contrast.

PMID- 18318423
TI  - Within-trial contrast: when you see it and when you don't.
AB  - Within-trial contrast occurs when a discriminative stimulus that is preceded by a
      relatively aversive event is preferred over another that is preceded by a less
      aversive event. Recent failures to replicate (Arantes & Grace, 2008; Vasconcelos,
      Urcuioli, & Lionello-DeNolf, 2007) may allow us to identify factors that may be
      responsible. In the case of Vasconcelos et al., it is likely that insufficient
      training was provided (often 35-65 sessions are required). In the case of Arantes
      and Grace (Experiment 2), these pigeons had been involved in prior experiments
      involving lean schedules of reinforcement, and we find that prior experience its
      occurrence. with lean (relatively aversive) schedules appears to reduce the
      presumed aversiveness of the many-peck requirement, thus obviating the contrast
      effect. Finally, in the case of Vasconcelos and Urcuioli (2008), although the
      contrast effect with a simultaneous discrimination was not reliable, it was not
      reliably smaller than with a successive discrimination that did show a reliable
      effect, and the contrast effect was also similar in magnitude to a reliable
      effect reported by Kacelnik and Marsh (2002). Thus, although there have been
      several failures to replicate the original effects reported by Clement, Feltus,
      Kaiser and Zentall (2000), insufficient training, prior history with lean
      schedules of reinforcement, and low statistical power may have been responsible
      for those failures.

PMID- 18318424
TI  - Response-cost punishment with pigeons: further evidence of response suppression
      via token loss.
AB  - Four pigeons responded on a two-component multiple token-reinforcement schedule,
      in which tokens were produced according to a random-interval 30-sec schedule and
      exchanged according to a variable-ratio 4 schedule in both components. To assess
      the effects of contingent token loss, tokens were removed after every second
      response (i.e., fixed-ratio 2 loss) in one of the components. Response rates were
      selectively lower in the loss components relative to baseline (no-loss)
      conditions, as well as to the within-condition no-loss components. Response rates
      were decreased to a greater degree in the presence of tokens than in their
      absence. To control for the effects of changes in the density of token and food
      reinforcement, two parts consisted of additional conditions where food density
      and token loss were yoked to those in a previous loss condition. In the yoked
      food condition, tokens were produced as usual in both components, but the overall
      density of food reinforcement in one of the components was yoked to that obtained
      during a previous token-loss condition. In the yoked token-loss condition, tokens
      were removed during one component of the multiple schedule at a rate that
      approximately matched the obtained rate of loss from a previous token-loss
      condition. Response rates in these yoked components were less affected than those
      in comparable loss components, despite similar densities of token, exchange, and
      food reinforcement. On the whole, the results support the conclusion that
      contingent token loss serves as an effective punisher with pigeons.

PMID- 18318425
TI  - Rats show preference for delayed rewards on the radial maze.
AB  - Rats on an eight-arm radial maze chose between four arms on which a small reward
      could be obtained after a short delay and four arms on which a larger reward
      could be obtained after a longer delay. Experiments 1 and 2 showed that rats
      preferred the long-delay, large-reward arms over the short-delay, small-reward
      arms. This preference was particularly marked when the arms were made into
      enclosed alleys. Experiment 3 showed that this effect was not produced by a
      preference for staying in enclosed alleys. We argue that the rats endured longer
      delays to obtain larger rewards when fear of predation was minimized.

PMID- 18318426
TI  - Required pecking and refraining from pecking alter judgments of time by pigeons.
AB  - There is evidence that humans' perception of time is affected by the activity in
      which they are engaged while they are timing. The more demanding the task, the
      faster time appears to pass. A similar effect has been found in pigeons. Pigeons
      trained to discriminate between a short-duration (2-sec) and a long-duration (10
      sec) stimulus were required to peck when the stimulus was one color and to
      refrain from pecking when it was a different color. On probe trials of
      intermediate durations, the bisection point (50% choice of the stimulus
      associated with both long and short stimuli) for trials in which the pigeons were
      required to peck was almost 1 sec longer than on trials in which the pigeons were
      required to refrain from pecking (Zentall, Friedrich, & Clement, 2006). In the
      present research, we replicated this effect and determined the relation between
      this effect and the typical bisection point that occurs when pecking is permitted
      but not required. Results indicated that the typical procedure results in a
      bisection point that is between required pecking and refraining from pecking.
      Furthermore, the rate of pecking when pecking is allowed but not required also
      falls between the rate of pecking for the required-pecking and refrain-from
      pecking conditions. This result suggests that, similar to humans, pigeons
      underestimate the passage of time when they are active or when attention to time
      related cues has to be shared with attention to satisfying the response
      requirement.

PMID- 18318427
TI  - Potentiation of taste and extract stimuli in conditioned flavor preference
      learning.
AB  - In these experiments, we investigated the nature of potentiation in the
      conditioned flavor preference paradigm. Almond and banana extracts, which have
      strong odor components, were combined with salt and saccharin (liked tastes;
      Experiment 1) or quinine and citric acid (disliked tastes; Experiment 2) in a
      flavor preference procedure that mixed these solutions with a caloric reinforcer
      (polycose). The results showed that liked tastes potentiated preference
      conditioning to extracts (Experiment 1), whereas extracts potentiated preference
      conditioning to disliked tastes (Experiment 2). In both experiments, the
      presumably less liked stimulus (i.e., the extract in Experiment 1 and the
      disliked taste in Experiment 2) was the potentiated cue.

PMID- 18318428
TI  - CYP1A1, SULT1A1, and SULT1E1 polymorphisms are risk factors for endometrial
      cancer susceptibility.
AB  - BACKGROUND: In estrogen biosynthetic pathways, many enzymes are important for
      metabolism, detoxification, and bioavailability. Polymorphisms in these genes may
      have an effect on the enzymes' function. For example, higher expression and
      activation of biosynthetic enzymes and lower expression and activation of
      conjugation enzymes may lead to high toxicity or carcinogenesis. The authors
      hypothesized that single nucleotide polymorphisms (single nucleotide
      polymorphisms) of CYP1A1, CYP1A2, CYP1B1, CYP17, SULT1A1, SULT1E1, and SHBG genes
      may be risk factors for endometrial cancer. METHODS: DNA samples from 150 cases
      of endometrial cancer and healthy controls (n = 165) were analyzed by polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine
      the genotypic frequency of 13 different polymorphic loci on the CYP1A1 (m1, m2,
      m3, m4), CYP1A2 1F, CYP1B1 codon432, COMT codon158, CYP17, SULT1A1 (Arg213His,
      14A/G, 85C/T in the 3' flanking region), SULT1E1-64G/A promoter region, and SHBG
      genes. Genotyping was validated by direct DNA sequencing. The authors also
      investigated the relation between expression of CYP1A1 in endometrial cancer
      tissues and genotypes of CYP1A1 m1. RESULTS: A decreased frequency of TC + CC
      genotype of the CYP1A1 m1 (T/C) polymorphism was observed in endometrial cancer
      patients compared with controls (OR = 0.42; 95% CI, 0.27-0.69). The T-A haplotype
      of CYP1A1 m1 and m2 was increased in endometrial cancer patients (P = .017). The
      frequency of CYP1A1 m1 T/C + C/C was higher in a high CYP1A1 expression group (P
      = .009). The authors also found that individuals carrying the variants of SULT1A1
      codon213 and 2 single nucleotide polymorphisms in the 3' flanking region (14A/G
      and 85C/T) had an increased risk for endometrial cancer. The frequencies of G-A-C
      and A-G-T haplotypes of these 3 variants were higher in endometrial cancer
      patients (P < .0001; P = .0002). In addition, the frequency of combined genotypes
      (SULT1A1 213 GA + AA and CYP1A1 m1 TT) was higher in endometrial cancer patients.
      (OR, 4.58; 95% CI, 2.35-8.93). CONCLUSIONS: This is the first report on the
      combined association of CYP1A1 and SULT gene polymorphisms in endometrial cancer
      that suggests a decreased single nucleotide polymorphism of CYP1A1 and an
      increased single nucleotide polymorphism for SULT1A1 and SULT1E1 genes may be
      risk factors for endometrial cancer in Caucasians.

PMID- 18318429
TI  - Phase II study of topotecan in combination with dexamethasone, asparaginase, and
      vincristine in pediatric patients with acute lymphoblastic leukemia in first
      relapse.
AB  - BACKGROUND: The authors evaluated the response rate, toxicity, and
      pharmacokinetics of topotecan given before standard induction therapy for
      childhood acute lymphoblastic leukemia (ALL) in first relapse. METHODS: Patients
      received topotecan (2.4 mg/m(2) daily as a 30-minute infusion) for 5 days before
      induction therapy with dexamethasone, vincristine, and asparaginase (native or
      pegylated Escherichia coli). The pharmacokinetics of topotecan were measured with
      the first dose of treatment in 23 patients. RESULTS: Twenty-eight of 31 patients
      with circulating blast cells were evaluable for response to topotecan. Twenty
      five patients (89.3%) had a response (>25% decrease in circulating blast cells).
      The leukocyte count (P = .0001) and blast cell count (P = .0009) declined
      significantly during topotecan therapy. The median (range) topotecan lactone area
      under the concentration-time curve after the first dose was 85.4 L/hour/m(2)
      (range, 38.7-229.3 L/hour/m(2)). At the end of induction, 23 patients (74.2%) had
      a complete response, 1 patient (3.2%) had a partial response, 5 patients (16.1%)
      had no response, and 2 patients had died of infection. Six of the 17 patients who
      were studied for minimal residual disease (MRD) achieved MRD-negative status at
      the end of induction. The main toxicities were hematologic, gastrointestinal, and
      hepatic. The estimated 5-year survival rate, event-free survival rate, and
      cumulative incidence of second relapse were 24.1% +/- 7.9%, 18.2% +/- 7.4%, and
      22.8% +/- 8.7%, respectively, in the 29 patients who had a hematologic first
      relapse. CONCLUSIONS: A regimen comprising single-agent topotecan given with a
      standard 3-drug combination was effective in inducing remission in pediatric
      patients with relapsed ALL and was tolerated well.

PMID- 18318430
TI  - An ethical argument in support of interactions between developing world countries
      and pharmaceutical/biotechnology companies involved in oncology drug development.

PMID- 18318431
TI  - Establishing treatment benchmarks for mammography-screened breast cancer
      population based on a review of evidence-based clinical guidelines.
AB  - BACKGROUND: No benchmarks exist in the screened breast cancer population to
      establish the optimal proportions of newly detected cancer patients who should
      receive the ideal treatment. The aim of the study was to estimate the optimal
      proportion of cases diagnosed in a breast-screening program who should receive
      treatment according to evidence-based cancer treatment guidelines and to compare
      these optimal rates with actual treatment rates. METHOD.: Optimal surgery,
      radiotherapy, chemotherapy, and hormone therapy utilization trees were
      constructed based on indications from evidence-based treatment guidelines. The
      proportions with clinical attributes that indicated a possible benefit from a
      particular treatment were obtained from epidemiologic data from BreastScreen
      Victoria. The optimal proportions of screen-detected breast cancer patients who
      should receive various therapies were then calculated using TreeAge software and
      compared with the actual proportions obtained from the epidemiologic data.
      RESULTS: According to the best available evidence, the proportion of screen
      detected breast cancer patients who have attributes suitable for various
      treatments are: breast-conserving surgery (BCS) 85%, mastectomy 15%, radiotherapy
      87%, chemotherapy 34%, and hormonal therapy 68%. The actual BCS utilization rate
      in Victoria was similar to the optimal rate (79% vs 85%), whereas there appeared
      to be underuse of radiotherapy (62% vs 87%), chemotherapy (19% vs 34%), and
      hormonal therapy (49% vs 68%) when compared with guideline recommendations.
      CONCLUSIONS: This research provided optimal treatment utilization rates for
      screen-detected breast cancer and a comparison of best practice evidence and
      actual treatment. The results showed comparable rates for surgery but suggested
      underutilization of radiotherapy, chemotherapy, and hormone therapy.

PMID- 18318432
TI  - Primary central nervous system lymphoma: monocenter, long-term, intent-to-treat
      analysis.
AB  - BACKGROUND: This retrospective, single-center study assessed the feasibility,
      outcome, and late side effects of the treatment of immunocompetent patients with
      primary central nervous system lymphoma (PCNSL) at the authors' institution.
      METHODS: All 72 consecutive patients diagnosed with PCNSL between January 1994
      and February 2005 were scheduled to receive high-dose methotrexate (HDMTX)-based
      chemotherapy. RESULTS: The median age of the patients was 62 years and the median
      Karnofsky performance score (KPS) was 70. Twelve patients did not receive HDMTX
      based chemotherapy because of poor physical condition or renal insufficiency. Of
      the 60 patients treated with HDMTX-based chemotherapy, the treatment of 9 was
      followed with whole-brain irradiation. Of 54 patients who were evaluable for
      response, 35 (65%) responded (52% with a complete response and 13% with a partial
      response), and 19 patients (35%) did not. At a median follow-up of 58.7 months,
      the median progression-free survival was 9 months and the median overall survival
      (OAS) was 41.4 months. According to the Memorial Sloan-Kettering Cancer Center
      (MSKCC) prognosis score, patients could be divided into 3 groups with
      significantly different OAS: 52.9 months for patients aged <50 years, 42.4 months
      for patients aged >or= 50 years and with a KPS >70, and 5.2 months for patients
      aged >or= 50 years and with a KPS <70 (P= .009, log-rank test). CONCLUSIONS:
      Promising long-term results could be achieved with HDMTX-based chemotherapy in
      patients with PCNSL in this monocenter study. The MSKCC score proved useful for
      predicting survival.

PMID- 18318433
TI  - Etanercept therapy and acute myeloid leukemia.

PMID- 18318434
TI  - Inflammation induces tau pathology in inclusion body myositis model via glycogen
      synthase kinase-3beta.
AB  - OBJECTIVE: Inclusion body myositis (IBM) is an inflammatory muscle disease,
      although the role of inflammation remains to be elucidated. Here, we address the
      mechanisms by which inflammation modulates Abeta and tau, two hallmark features
      of this disease. METHODS: A transgenic mouse model of IBM was utilized in which
      acute and chronic inflammation was induced via lipopolysaccharide. The effects of
      inflammation were assessed by analyzing the myopathological and the behavioral
      phenotype. Human IBM skeletal muscle biopsies were investigated to determine
      concordance with data from the animal model. RESULTS: Both acute and chronic
      lipopolysaccharide exposure augmented infiltration by CD8(+) cytotoxic T cells
      and increased amyloid precursor protein steady-state levels in skeletal muscle,
      whereas increased Abeta generation was observed only in chronically treated mice.
      Both acute and chronic inflammation enhanced tau phosphorylation in skeletal
      muscle. The mechanism underlying this effect was mediated by the tau kinase,
      glycogen synthase kinase-3beta (GSK-3beta). Suppression of GSK-3beta activity
      using either a specific inhibitor or lithium chloride significantly reduced tau
      phosphorylation and partially rescued motor impairment. In human IBM muscle, GSK
      3beta and phospho-tau were colocalized, further supporting the pathogenic role of
      GSK-3beta in this disease. Using C2C12 myoblast cultures, we found that GSK-3beta
      was activated by proinflammatory cytokines (interleukin-1beta, interleukin-6,
      tumor necrosis factor-alpha), leading to enhanced tau phosphorylation.
      INTERPRETATION: Our results identify a molecular mechanism by which
      proinflammatory stimuli affect tau pathology via the GSK-3beta signaling pathway
      in skeletal muscle.

PMID- 18318435
TI  - Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling,
      and decreases survival in hepatocellular carcinoma.
AB  - It has been shown that the heparin-degrading endosulfatase, sulfatase 1 (SULF1),
      functions as a liver tumor suppressor, but the role of the related sulfatase,
      sulfatase 2 (SULF2), in liver carcinogenesis remains to be elucidated. We
      investigated the effect of SULF2 on liver tumorigenesis. Expression of SULF2 was
      increased in 79 (57%) of 139 hepatocellular carcinomas (HCCs) and 8 (73%) of 11
      HCC cell lines. Forced expression of SULF2 increased HCC cell growth and
      migration, whereas knockdown of SULF2 using short hairpin RNA targeting SULF2
      abrogated HCC cell proliferation and migration in vitro. Because SULF1 and SULF2
      desulfate heparan sulfate proteoglycans (HSPGs) and the HSPG glypican 3 (GPC3) is
      up-regulated in HCC, we investigated the effects of SULF2 on GPC3 expression and
      the association of SULF2 with GPC3. SULF2-mediated cell growth was associated
      with increased binding of fibroblast growth factor 2 (FGF2), phosphorylation of
      extracellular signal-regulated kinase and AKT, and expression of GPC3. Knockdown
      of GPC3 attenuated FGF2 binding in SULF2-expressing HCC cells. The effects of
      SULF2 on up-regulation of GPC3 and tumor growth were confirmed in nude mouse
      xenografts. Moreover, HCC patients with increased SULF2 expression in resected
      HCC tissues had a worse prognosis and a higher rate of recurrence after surgery.
      CONCLUSION: In contrast to the tumor suppressor effect of SULF1, SULF2 has an
      oncogenic effect in HCC mediated in part through up-regulation of FGF signaling
      and GPC3 expression.

PMID- 18318436
TI  - Thrombosis and anticoagulation in liver disease.

PMID- 18318437
TI  - Mortality attributable to cholestatic liver disease in the United States.
AB  - In the past 2 decades, important advances have been made in the treatment of
      cholestatic liver diseases, including primary biliary cirrhosis (PBC) and primary
      sclerosing cholangitis (PSC). Whether these new therapies have had demonstrable
      impact on mortality on a population-wide scale has not been evaluated. This study
      describes the age-specific and sex-specific mortality rates from PBC and PSC in
      the United States between 1980 and 1998, based on the Multiple Cause of Death
      files. Age-specific and sex- specific mortality rates from PBC and PSC were
      calculated. The multivariable Poisson model was used to evaluate temporal changes
      in mortality rates. In 1998, the total age-adjusted and sex-adjusted PBC-related
      mortality rate was 0.24 per 100,000, and the age-adjusted and sex-adjusted PSC
      related mortality rate was 0.23 per 100,000. During the observation period, PBC
      related mortality significantly decreased over time in women younger than 65
      years, and in men of all age groups, whereas in older women this number increased
      over time. PSC-related mortality remained essentially stable, except in men 65
      years of age or older. CONCLUSION: Since the early 1980s, significant changes in
      mortality from PBC have occurred. The most noticeable change was an increase in
      the age of death, which indicates prolongation of survival. These changes may be
      attributable to liver transplantation or ursodeoxycholic acid. In contrast,
      mortality from PSC remained largely unchanged, highlighting the need for more
      effective therapeutic strategies.

PMID- 18318438
TI  - Activation of liver X receptor sensitizes mice to gallbladder cholesterol
      crystallization.
AB  - Gallstone disease is a hepatobiliary disorder due to biochemical imbalances in
      the gallbladder bile. In this report, we show that activation of nuclear receptor
      liver X receptor (LXR) sensitized mice to lithogenic diet-induced gallbladder
      cholesterol crystallization, which was associated with dysregulation of several
      hepatic transporters that efflux cholesterol, phospholipids, and bile salts. The
      combined effect of increased biliary concentrations of cholesterol and
      phospholipids and decreased biliary concentrations of bile salts in LXR-activated
      mice led to an increased cholesterol saturation index and the formation of
      cholesterol crystals. Interestingly, the lithogenic effect of LXR was completely
      abolished in the low-density lipoprotein receptor (Ldlr) null background or when
      the mice were treated with Ezetimibe, a cholesterol-lowering drug that blocks
      intestinal dietary cholesterol absorption. These results suggest that LDLR
      mediated hepatic cholesterol uptake and intestinal cholesterol absorption play an
      essential role in LXR-promoted lithogenesis. CONCLUSION: The current study has
      revealed a novel lithogenic role of LXR as well as a functional interplay between
      LXR and LDLR in gallbladder cholesterol crystallization and possibly cholesterol
      gallstone disease (CGD). We propose that LXR is a lithogenic factor and that the
      LXR transgenic mice may offer a convenient CGD model to develop therapeutic
      interventions for this disease.

PMID- 18318439
TI  - Hemodynamic effects of urotensin II and its specific receptor antagonist
      palosuran in cirrhotic rats.
AB  - In cirrhosis, splanchnic vasodilation contributes to portal hypertension,
      subsequent renal sodium retention, and formation of ascites. Urotensin II(U-II)
      is a constrictor of large conductive vessels. Conversely, it relaxes mesenteric
      vessels, decreases glomerular filtration, and increases renal sodium retention.
      In patients with cirrhosis, U-II plasma levels are increased. Thus, we
      investigated hemodynamic and renal effects of U-II and its receptor antagonist,
      palosuran, in cirrhotic bile duct-ligated rats (BDL). In BDL and sham-operated
      rats, we studied acute effects of U-II (3 nmol/kg; intravenously) and palosuran
      (10 mg/kg; intravenously) and effects of oral administration of palosuran (30
      mg/kg/day; 3 days) on hemodynamics and renal function. We localized U-II and U-II
      receptor (UTR) in livers and portal veins by immunostaining. We determined U-II
      plasma levels by enzyme-linked immunosorbent assay (ELISA), and mesenteric
      nitrite/nitrate-levels by Griess-reaction. RhoA/Rho-kinase and endothelial nitric
      oxide synthase (eNOS) pathways were determined by western blot analysis and
      reverse transcription polymerase chain reaction (RT-PCR) in mesenteric arteries.
      U-II plasma levels, as well as U-II and UTR-receptor expression in livers and
      portal veins of cirrhotic rats were significantly increased. U-II administration
      further augmented the increased portal pressure (PP) and decreased mean arterial
      pressure (MAP), whereas palosuran decreased PP without affecting MAP. The
      decrease in PP was associated with an increase in splanchnic vascular resistance.
      In mesenteric vessels, palosuran treatment up-regulated expression of RhoA and
      Rho-kinase, increased Rho-kinase-activity, and diminished nitric oxide
      (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) signaling. Moreover, palosuran
      increased renal blood flow, sodium, and water excretion in BDL rats. CONCLUSION:
      In BDL rats, U-II is a mediator of splanchnic vasodilation, portal hypertension
      and renal sodium retention. The U-II-receptor antagonist palosuran might
      represent a new therapeutic option in liver cirrhosis with portal hypertension.

PMID- 18318440
TI  - Acute liver failure: Summary of a workshop.
AB  - Acute liver failure (ALF) is a rare but challenging clinical syndrome with
      multiple causes; a specific etiology cannot be identified in 15% of adult and 50%
      of pediatric cases. The course of ALF is variable and the mortality rate is high.
      Liver transplantation is the only therapy of proven benefit, but the rapidity of
      progression and the variable course of ALF limit its use. Currently in the United
      States, spontaneous survival occurs in approximately 45%, liver transplantation
      in 25%, and death without transplantation in 30% of adults with ALF. Higher rates
      of spontaneous recovery (56%) and transplantation (31%) with lower rates of death
      (13%) occur in children. The outcome of ALF varies by etiology, favorable
      prognoses being found with acetaminophen overdose, hepatitis A, and ischemia
      (approximately 60% spontaneous survival), and poor prognoses with drug-induced
      ALF, hepatitis B, and indeterminate cases (approximately 25% spontaneous
      survival). Excellent intensive care is critical in management of patients with
      ALF. Nonspecific therapies are of unproven benefit. Future possible therapeutic
      approaches include N-acetylcysteine, hypothermia, liver assist devices, and
      hepatocyte transplantation. Advances in stem cell research may allow provision of
      cells for bioartificial liver support. ALF presents many challenging
      opportunities in both clinical and basic research.

PMID- 18318441
TI  - Changing trends in hepatitis C-related mortality in the United States, 1995-2004.
AB  - The disease burden and mortality from hepatitis C are predicted to increase in
      the United States as the number of persons with long-standing chronic infection
      grows. We analyzed hepatitis C mortality rates derived from US Census and
      multiple-cause-of-death data for 1995-2004. Deaths were considered hepatitis C
      related if: (1) hepatitis C was the underlying cause of death, (2) chronic liver
      disease was the underlying cause and hepatitis C was a contributing cause, or (3)
      human immunodeficiency virus was the underlying cause and chronic liver disease
      and hepatitis C were contributing causes. A total of 56,409 hepatitis C-related
      deaths were identified. Mortality rates increased 123% during the study period
      (1.09 per 100,000 persons to 2.44 per 100,000), but average annual increases were
      smaller during 2000-2004 than 1995-1999. After peaking in 2002 (2.57 per
      100,000), overall rates declined slightly, but continued to increase among
      persons aged 55-64 years. Overall increases were greater among males (144%) than
      females (81%) and among non-Hispanic blacks (170%) and Native Americans (241%)
      compared to non-Hispanic whites (124%) and Hispanics (84%). The 7,427 hepatitis C
      deaths in 2004 (mean age: 55 years), corresponded to 148,611 years of potential
      life lost. The highest mortality rates in 2004 were observed among males, persons
      aged 45-54 and 55-64 years, Hispanics, non-Hispanic blacks, and non-Hispanic
      Native American/Alaska Natives. CONCLUSION: Overall, hepatitis C mortality has
      increased substantially since 1995. Despite small declines in recent years, rates
      have continued to increase among persons aged 55-64 years. Hepatitis C is an
      important cause of premature mortality.

PMID- 18318442
TI  - Loss of the glycine N-methyltransferase gene leads to steatosis and
      hepatocellular carcinoma in mice.
AB  - Glycine N-methyltransferase (GNMT) is the main enzyme responsible for catabolism
      of excess hepatic S-adenosylmethionine (SAMe). GNMT is absent in hepatocellular
      carcinoma (HCC), messenger RNA (mRNA) levels are significantly lower in livers of
      patients at risk of developing HCC, and GNMT has been proposed to be a tumor
      susceptibility gene for liver cancer. The identification of several children with
      liver disease as having mutations of the GNMT gene further suggests that this
      enzyme plays an important role in liver function. In the current study we studied
      development of liver pathologies including HCC in GNMT-knockout (GNMT-KO) mice.
      GNMT-KO mice have elevated serum aminotransferase, methionine, and SAMe levels
      and develop liver steatosis, fibrosis, and HCC. We found that activation of the
      Ras and Janus kinase (JAK)/signal transducer and activator of transcription
      (STAT) pathways was increased in liver tumors from GNMT-KO mice coincidently with
      the suppression of the Ras inhibitors Ras-association domain family/tumor
      suppressor (RASSF) 1 and 4 and the JAK/STAT inhibitors suppressor of cytokine
      signaling (SOCS) 1-3 and cytokine-inducible SH2-protein. Finally, we found that
      methylation of RASSF1 and SOCS2 promoters and the binding of trimethylated lysine
      27 in histone 3 to these 2 genes was increased in HCC from GNMT-KO mice.
      CONCLUSION: These data demonstrate that loss of GNMT induces aberrant methylation
      of DNA and histones, resulting in epigenetic modulation of critical carcinogenic
      pathways in mice.

PMID- 18318443
TI  - Blocking transforming growth factor-beta up-regulates E-cadherin and reduces
      migration and invasion of hepatocellular carcinoma cells.
AB  - Hepatocellular carcinoma (HCC) treatment is challenging because the mechanisms
      underlying tumor progression are still largely unknown. Transforming growth
      factor (TGF)-beta1 is considered a crucial molecule in HCC tumorigenesis because
      increased levels of patients' serum and urine are associated with disease
      progression. The aim of the present study was to investigate the inhibition of
      TGF-beta signaling and its impact on HCC progression. Human HCC cell lines were
      treated with a TGF-beta receptor kinase inhibitor (LY2109761) whose selectivity
      was determined in a kinase assay. Exogenous TGF-beta1 phosphorylates the TGF-beta
      receptor, consequently activating Smad-2, whereas the drug selectively blocks
      this effect and dephosphorylates autocrine p-Smad-2 at concentrations ranging
      from 0.001 to 0.1 microM. A cytotoxic effect documented by 3-[4,5-dimethylthiazol
      2-yl]-2,5-diphenyltetrazolium bromide (MTT), trypan blue, and propidium iodide
      staining assays was observed at 10microM, whereas the drug inhibits (P < 0.001)
      the migration of HCC cells on fibronectin, laminin-5, and vitronectin and
      invasion through Matrigel (P < 0.001) at concentrations up to 0.1 microM.
      LY2109761 up-regulates (P < 0.001) E-cadherin mRNA and protein levels. This
      increase was localized at the cellular membrane where E-cadherin mediates
      anchorage that is cell-cell dependent. Consistently, a functional monoclonal
      antibody that inhibits E-cadherin-dependent cell-cell contact restores the
      migratory and invasive activity. Finally, nonmetastatic HCC tissues from 7
      patients were cultured with TGF-beta1 in the presence or absence of LY2109761. E
      cadherin expression was reduced by TGF-beta1 and was significantly (P < 0.0001)
      increased by LY2109761 treatment, measured by quantitative real-time PCR on
      microdissected tissues and by immunohistochemistry on serial sections. In 72
      patients, E-cadherin tissue expression was more weakly expressed in metastatic
      than in nonmetastatic HCC (P < 0.0001). CONCLUSION: LY2109761 blocks migration
      and invasion of HCC cells by up-regulating E-cadherin, suggesting that there
      could be a mechanistic use for this molecule in clinical trials.

PMID- 18318444
TI  - Antibacterial hydrogels of amino acid-based cationic amphiphiles.
AB  - Development of biomaterials, which are inherently antibacterial having broad
      spectrum activity against both Gram-positive and Gram-negative bacteria with
      considerable biocompatibility, is of tremendous importance in biomedicinal
      chemistry. Microbial infections are still of great concern, often originated from
      indwelling medical devices typically in hospitalized patients. To this end,
      hydrogelating soft materials particularly from low-molecular-weight (LMW)
      gelators have generated significant interest in preparing and modifying
      biomedicinal implants. Herein, we have developed L-tryptophan based cationic
      amphiphilic hydrogelators with varying degree of hydrophobicity that exhibited
      remarkable bactericidal activity against wide range of Gram-positive (MIC = 0.1
      75 microg/mL) and Gram-negative bacteria (MIC = 0.5-5 microg/mL). Antimicrobial
      efficacy of the amphiphiles was greatly influenced by their alkyl chain length.
      This bactericidal effect of cationic hydrogelators is quite comparable or in some
      cases markedly better than that of clinically available antibiotics. Most
      excitingly, they selectively attack the bacterial pathogens while remain
      biocompatible to the mammalian cells. Thus, we have developed LMW biocompatible,
      inherently antibacterial hydrogels having potential applications in biomedicines.

PMID- 18318445
TI  - A role for microwave processing in the dry preservation of mammalian cells.
AB  - Dry preservation involves removing water from samples so that degradative
      biochemical processes are slowed and extended storage is possible. Recently this
      approach has been explored as a method for preserving living mammalian cells. The
      current work explores the use of microwave processing to enhance evaporation
      rates and to improve drying uniformity, thereby overcoming some of the challenges
      in this field. Mouse macrophage cells (J774) were pre-incubated in full
      complement media containing 50 mM trehalose, for 18-h, to allow for endocytosis
      of trehalose. Droplets of experimental and control (no intracellular trehalose)
      cell suspensions were placed on coverslips in a microwave cavity. Water was
      evaporated using intermittent microwave heating (600 W, 30 s intervals). Samples
      were dried to various moisture levels, rehydrated, and then survival was assessed
      after a 45-min recovery period using Calcein-AM/PI fluorescence and Trypan Blue
      exclusion assays. The metabolic activity of dried cells (4.3 gH(2)O/gdw) was
      assessed after rehydration using a resazurin reduction assay. Apoptosis levels
      were also measured. Post- rehydration survival correlated with the final moisture
      content achieved, consistent with other drying methods. Intracellular trehalose
      provided protection against injury associated with moisture loss. Metabolic
      assays revealed normal growth in surviving cells, and these survival levels were
      consistent with results from apoptosis assays (P > 0.05). Brightfield and
      fluorescence images of microwave-dried samples revealed a uniform distribution of
      cells within the dried matrix and profilometry analysis demonstrated that solids
      were uniformly distributed throughout the sample. Microwave-processing
      successfully facilitated rapid and uniform dehydration of cell-based samples.

PMID- 18318446
TI  - Combined use of supported liquid membrane and solid-phase extraction to enhance
      selectivity and sensitivity in capillary electrophoresis for the determination of
      ochratoxin A in wine.
AB  - This paper proposes a novel strategy to enhance selectivity and sensitivity in
      CE, using supported liquid membrane (SLM) and off-line SPE simultaneously. The
      determination of ochratoxin A (OA) in wine has been used to demonstrate the
      potential of this methodology. In the SLM step, the donor phase (either a 20 mL
      volume of a standard solution at pH 1 or a wine sample at pH 8) was placed in a
      vial, where a micromembrane extraction unit accommodating the acceptor phase (1
      mL water, pH 11) in its lumen was immersed. The SLM was constructed by
      impregnating a porous Fluoropore Teflon (PTFE) membrane with a water-immiscible
      organic solvent (octanol). In the off-line SPE step, the nonpolar sorbent (C-18,
      4 mg) selectively retained the target ochratoxin, enabling small volumes of
      acceptor phase (1 mL) to be introduced. The captured analytes were eluted in a
      small volume of methanol (0.1 mL). This procedure resulted in sample cleanup and
      concentration enhancement. The method was evaluated for accuracy and precision,
      and its RSD found to be 5%. The LODs for OA in the standard solutions and wine
      samples were 0.5 and 30 microg/L, respectively. The results obtained demonstrate
      that SLM combined with off-line is a good alternative to the use of
      immunoaffinity columns prior to CE analysis.

PMID- 18318447
TI  - Separation of membrane proteins by two-dimensional electrophoresis using cationic
      rehydrated strips.
AB  - Due to their poor solubility during IEF membrane proteins cannot be separated and
      analyzed satisfactorily with classical 2-DE. A more efficient method for such
      hydrophobic proteins is the benzyldimethyl-n-hexadecylammonium chloride (16
      BAC)/SDS-PAGE, but the corresponding protocol is intricate and time-consuming. We
      now developed an easy-to-handle electrophoresis method in connection with a novel
      device which enables reproducible separation of ionic solubilized membrane
      proteins using individually rehydrated plastic sheet gel strips. These strips are
      suitable for the first dimension in a 2-D 16-BAC/SDS system and can be handled
      easily; this is demonstrated by the separation of membrane proteins of human
      embryonic kidney (HEK293) cells.

PMID- 18318448
TI  - Improved adapter-ligation-mediated allele-specific amplification for multiplex
      genotyping by using software.
AB  - Adapter-ligation-mediated allele-specific amplification (ALM-ASA) is a potential
      method for multiplex SNPs typing at an ultra low cost. Here, we describe a kind
      of software, which designs allele-specific primers for ALM-ASA assay on multiplex
      SNPs. DNA sequences containing SNPs of interest are submitted into the software
      which contains various endonucleases for options. Based on the SNP sequence
      information and the selected endonucleases, the software is capable of
      automatically generating sets of information needed to perform genotyping
      experiments. Each set contains a suitable endonuclease, qualified allele-specific
      primers with orientations and melting temperatures, sizes of allele-specific
      amplicons, and gel electropherograms simulated according to the sizes of the
      allele-specific amplicons and the mobility of DNA fragments in 2% agarose gel.
      Seven SNPs in the arylamines N-acetyltransferase 2 (NAT2) gene, five SNPs in the
      BRCA1 gene, five SNPs in the COMT gene, six SNPs in the CYP2E1 gene, five SNPs in
      the MPO gene, and six SNPs in the NRG1 gene were selected for evaluating the
      software. Without extra optimization, seven SNPs in the NAT2 gene were
      successfully genotyped for genomic DNA samples from 127 individuals by using the
      first set of allele-specific primers yielded by the software. Although several
      steps are used in the ALM-ASA assay, the whole genotyping process can be
      completed within 3 h by optimizing each step. Profiting from the software, the
      ALM-ASA assay is easy-to-perform, labor-saving, and accurate.

PMID- 18318449
TI  - Interaction of humic acids with human DNA: proposed mechanisms and kinetics.
AB  - Human DNA quantification by quantitative real-time PCR (QRT-PCR) has gained great
      importance in forensic DNA and ancient DNA studies. However, in such samples, DNA
      quantification is impaired by the frequently present humic acid (HA). We have
      previously shown that the addition of synthetic HA inhibits QRT-PCR. In this
      study we investigated the possible mechanisms of HA interaction with human DNA,
      and kinetics of QRT-PCR inhibition. In QRT-PCR with pure human DNA and no HA
      added, VMAX was 40. With DNA sample containing 4 microg/mL of HA, VMAX was 30.30
      while the addition of extra Taq polymerase to the same sample changed VMAX into
      38.91, amplifying between 80 and 90% of input DNA. The KM/VMAX ratio in all the
      samples remained constant, indicating that the mechanism of HA inhibition of QRT
      PCR is uncompetitive by nature. Moreover, HA shifts the human DNA melting
      temperature point (Tm) from 75 to 87 degrees C and inhibits DNase I-mediated DNA
      cleavage, most probably affecting the enzyme's activity.

PMID- 18318450
TI  - Diastereomeric difference of inclusion modes between (-)-epicatechin gallate, (-)
      epigallocatechin gallate and (+)-gallocatechin gallate, with beta-cyclodextrin in
      aqueous solvent.
AB  - Inclusion complexes of (-)-epicatechin gallate (ECg) as well as (+)-gallocatechin
      gallate (GCg) and beta-cyclodextrin (beta-CD) in an aqueous solution were
      investigated using several NMR techniques and a computational method. ECg and
      EGCg formed a 1:1 complex with beta-CD, in which the A ring and a portion of the
      C ring were included from the wide secondary hydroxyl group side of the beta-CD
      cavity, and the B and B' rings were left outside the cavity. GCg formed a 1:2
      complex with beta-CD, in which the A and B rings of GCg were included by two
      molecules of beta-CD. The difference between the two modes of inclusion of the
      1:1 complex of ECg, EGCg.beta-CD and the 1:2 complex of GCg.beta-CD might have
      resulted from the size of the space between the B and B' rings in aqueous
      solution. As a result of nuclear Overhauser effect (NOE) experiments, GCg was
      considered to have a large enough space between the B and B' rings to include the
      B ring in the beta-CD cavity; on the other hand, ECg and EGCg have no such large
      space.

PMID- 18318451
TI  - Characterization of two hydroxytrichloropicolinic acids: application of the one
      bond chlorine-isotope effect in 13C NMR.
AB  - The structures of 4-hydroxy-3,5,6-trichloropyridine-2-carboxylic acid (1a) and 6
      hydroxy-3,4,5-trichloro-2-carboxylic acid (1b) were verified by the NMR analysis
      of their corresponding methylated and decarboxylated derivatives 2,3,5-trichloro
      4-methoxypyridine (5) and 3,4,5-trichloro-2-methoxypyridine (8), respectively.
      The 6-hydroxy isomer (1a) was found to be in equilibrium with its pyridinone
      tautomer as evidenced by the formation of significant amounts of 3,4,5-trichloro
      1-methyl-6-oxo-1,6-dihydropyridine-2-carboxylic acid methyl ester (6b) on
      exhaustive methylation. The one-bond chlorine-isotope effect was used and shown
      to be an effective tool for the identification of chlorinated carbons in (13)C
      NMR spectra providing an additional tool for solving structural problems in
      chlorinated compounds.

PMID- 18318452
TI  - Comparative analysis of hydrogen bonding with participation of the nitrogen,
      oxygen and sulfur atoms in the 2(2'-heteroaryl)pyrroles and their trifluoroacetyl
      derivatives based on the 1H, 13C, 15N spectroscopy and DFT calculations.
AB  - The N-H...X (X = N,O,S) intramolecular hydrogen bond in the series of 2(2'
      heteroaryl)pyrroles and their trifluoroacetyl derivatives is examined by the
      (1)H, (13)C, (15)N spectroscopy and density functional theory (DFT) calculations.
      The influence of the hydrogen bond on coupling and shielding constants is
      considered. It is shown that the N-H...N intramolecular hydrogen bond causes a
      larger increase in the absolute size of the (1)J(N,H) coupling constant and a
      larger deshielding of the bridge proton than the N-H...O hydrogen bond. The
      effect of the N-H...S interaction on the (1)J(N,H) coupling constant and the
      shielding of the bridge proton is small. The NMR parameter changes in the series
      of the 2(2'-heteroaryl)pyrroles due to N-H...X hydrogen bond and the series of
      the 1-vinyl-2-(2'-heteroaryl)-pyrroles due to C-H...X hydrogen bond have the same
      order. The proximity of the nitrogen, oxygen or sulfur lone pair to the F...H
      hydrogen bridge quenches the trans-hydrogen bond spin-spin couplings (1h)J(F,H-1)
      and (2h)J(F,N).

PMID- 18318453
TI  - Adolescent's stress responses and psychological functioning when a parent has
      early breast cancer.
AB  - OBJECTIVE: To identify factors associated with psychological functioning in
      adolescent children of early-stage breast cancer patients. METHOD: Adolescents'
      self-reported psychological functioning using the Child Behaviour Checklist
      (YSR), Mental Health subscale of the Child Health Questionnaire (CHQ-MH) and
      Child Impact of Events (C-IES) scale. The Family Assessment Device (FAD) and the
      Family Environment Scale (FES cohesion subscale) assessed family functioning.
      Maternal depression was assessed on the Beck Depression Inventory (BDI) and
      quality of life using the SF8. Using a cross-sectional within-groups design,
      assessments were obtained for 56 adolescents of 11-17 years . RESULTS: High rates
      of stress were found (C-IES) in 33% males and 45% females. Thirty percent of
      adolescents reported psychological problems (YSR) (28% males and 32% females)
      when compared with published norms. Poor family functioning was linked with YSR
      internalising and externalising problems; poor family cohesion with higher
      externalising and total YSR psychological problems. Maternal depression was
      linked with adolescent-reported internalising problems. CONCLUSIONS: When mothers
      have breast cancer, a substantial minority of their adolescent children have
      psychological and stress response-related problems linked with poor family
      functioning. These results argue in favour of a family-oriented approach to
      psychological support of breast cancer patients.

PMID- 18318454
TI  - Effects of psychological distress on quality of life of adult daughters and their
      mothers with cancer.
AB  - INTRODUCTION: As the population continues to age, adult daughters are more likely
      to be involved in caregiving. Given the fact that sharing emotional experiences
      is common in female relationships, (dis)similarity between mothers with cancer
      and their adult caregiving daughters is expected. However, the extent to which
      the (dis)similarity in psychological distress influences the quality of life of
      each person remains unknown. METHOD: This study aims at addressing this concern,
      using a total of 98 mother-daughter dyads participating in the American Cancer
      Society's Study of Cancer Survivors-I and Quality of Life Survey for Caregivers.
      RESULTS: Using the Actor Partner Interdependence Model, the results showed that
      although each person's psychological distress is the strongest predictor of their
      own quality of life, a mother's distress also plays a significant role in the
      daughter's quality of life. Specifically, when mothers experienced greater levels
      of psychological distress, the daughters reported better mental health but poorer
      physical health. CONCLUSIONS: Our findings on the disproportionately strong
      association between psychological distress of mothers with cancer and their adult
      caregiving daughters' quality of life suggest that caregiving daughters may
      benefit from programs designed to assist them to cope better with their mothers'
      psychological distress when both are living with cancer.

PMID- 18318455
TI  - Effects of lorazepam on visual perceptual abilities.
AB  - OBJECTIVE: To evaluate the effects of an acute dose of the benzodiazepine (BZ)
      lorazepam in young healthy volunteers on five distinguishable visual perception
      abilities determined by previous factor-analytic studies. METHODS: This was a
      double-blind, cross-over design study of acute oral doses of lorazepam (2 mg) and
      placebo in young healthy volunteers. We focused on a set of paper-and-pencil
      tests of visual perceptual abilities that load on five correlated but
      distinguishable factors (Spatial Visualization, Spatial Relations, Perceptual
      Speed, Closure Speed, and Closure Flexibility). Some other tests (DSST, immediate
      and delayed recall of prose; measures of subjective mood alterations) were used
      to control for the classic BZ-induced effects. RESULTS: Lorazepam impaired
      performance in the DSST and delayed recall of prose, increased subjective
      sedation and impaired tasks of all abilities except Spatial Visualization and
      Closure Speed. Only impairment in Perceptual Speed (Identical Pictures task) and
      delayed recall of prose were not explained by sedation. CONCLUSION: Acute
      administration of lorazepam, in a dose that impaired episodic memory, selectively
      affected different visual perceptual abilities before and after controlling for
      sedation. Central executive demands and sedation did not account for results, so
      impairment in the Identical Pictures task may be attributed to lorazepam's visual
      processing alterations.

PMID- 18318456
TI  - Catalytic effect of dissolved humic acids on the chemical degradation of
      phenylurea herbicides.
AB  - BACKGROUND: Although biodegradation seems to be the main cause of herbicide
      degradation, abiotic degradation can also be important for chemicals such as
      phenylureas, which are subject to catalysed soil reactions. The aim of this work
      is to investigate the effect of dissolved humic acids (HAs), normally present in
      natural waters, on the hydrolysis of phenylurea herbicides, and it presents a
      kinetic model that takes into account the role of adsorption. RESULTS: The
      linearity of the adsorption isotherms indicates that phenylurea-humic acid
      interaction can be considered in terms of a repartition-like equilibrium of
      phenylurea between water and HAs. Kinetic experiments show that the degradation
      rates of phenylureas increase with HA concentration. CONCLUSION: The kinetic
      equation adopted adequately describes the experimental data trend, allowing the
      evaluation of the catalytic effect of HAs on the chemical degradation of
      phenylureas. Carboxyl groups of HAs seem to play a leading role in the catalysis.
      The kinetic equation derived in this work could be helpful in predicting the
      persistence of phenylureas and of related compounds in natural water.

PMID- 18318457
TI  - Intestinal regeneration by a novel surgical procedure.
AB  - BACKGROUND: Treatment of short bowel syndrome is problematical. Small bowel
      tissue engineering has achieved modest results in animal studies. The aim of this
      study was to investigate intestinal regeneration in a novel surgical model.
      METHODS: Roux-en-Y bypass procedures were performed on 40 Wistar rats weighing
      250-350 g. Animals were killed at 1, 2, 3, 4, 8, 12 and 24 weeks after
      implantation with a 3-cm silicone tube. The spatio temporal relationship of
      intestinal regeneration was analysed using three-dimensional multislice computed
      tomography, and examination of sequential morphological changes on gross or
      histological findings and measurement of missing intestinal tissue (growth
      defects). RESULTS: Progressive intestinal regeneration on a silicone tube was
      identifiable in 35 animals. Most adhesions were initially localized on the tube
      but spread to a distal site 4 weeks after implantation. Growth defects decreased
      with time, with a marked reduction in the first 4 weeks and a gradual reduction
      to week 24 after implantation. Luminal patency shown radiologically as well as
      sequential histological findings, such as mucosal lining, matrix remodelling and
      muscular regeneration, suggested that regeneration of intestinal tissue took
      place, not merely scar contraction. CONCLUSION: Non-invasive as well as
      histomorphological assessment followed intestinal regeneration over time in this
      model, which provides scope for further studies.

PMID- 18318458
TI  - Frontomaxillary facial angle in trisomy 21 fetuses at 16-24 weeks of gestation.
AB  - OBJECTIVES: To establish a normal range for the frontomaxillary facial (FMF)
      angle by three-dimensional (3D) ultrasound imaging and to examine the FMF angle
      in trisomy 21 fetuses at 16-24 weeks of gestation. METHODS: We measured the FMF
      angle using 3D volumes of the fetal profile obtained with the transducer parallel
      to the long axis of the nose and at 45 degrees to the palate, which had been
      acquired from 150 normal fetuses and 23 fetuses with trisomy 21. RESULTS: In the
      normal group there was no significant association between the FMF angle and
      gestational age; the mean FMF angle was 83.9 degrees (range, 76.9-90.2 degrees )
      and the 95(th) centile was 88.5 degrees . In 15 (65.2%) of the fetuses with
      trisomy 21 the FMF angle was greater than 88.5 degrees . Repeatability studies
      demonstrated that in 95% of cases the difference between two measurements of FMF
      angle by the same operator and different operators was less than 5 degrees .
      CONCLUSIONS: In the majority of second-trimester fetuses with trisomy 21 the FMF
      angle is increased.

PMID- 18318459
TI  - Height of the cerebellar vermis and gestational age at birth.
AB  - OBJECTIVES: The objective of this study was to construct reference ranges of the
      neonatal cerebellar vermis height with respect to the gestational age at birth.
      METHODS: This observational study assessed 434 neonates born at 25-42 weeks'
      gestation. The neonates were singleton and appropriate in size for gestational
      age, and did not exhibit any abnormalities or neonatal disease. Gestational age
      was based on the date of the last menstrual period and confirmed by ultrasound
      examination performed within the 12(th) week of pregnancy. Sonographic
      measurements of the height of the cerebellar vermis in the mid-sagittal plane
      were performed within 24 h of birth by the same neonatal sonographer. Reference
      ranges (5(th), 50(th) and 95(th) centiles) were estimated by a mean and SD model
      based on least-squares polynomial regression. RESULTS: Neonatal sonographic
      measurements were obtained in all cases. Mean (SD) maternal age was 30.2 (4.3)
      years. Mean cerebellar vermis height adjusted for gestational age did not differ
      between males and females, the mean adjusted difference being 0.012 (95% CI, -
      0.009 to 0.033) cm. Mean cerebellar vermis height (cm) against gestational age
      (weeks) was suitably modeled by a linear-cubic polynomial as - 1.784 + 0.137 x GA
      - 0.000019 x GA(3) (SD = - 0.147 + 0.008 x GA), where GA = gestational age.
      CONCLUSIONS: Reference ranges for the height of the cerebellar vermis at birth
      with respect to gestational age at birth have been constructed in appropriate-for
      gestational-age neonates.

PMID- 18318460
TI  - A recombinant form of chagasin from Trypanosoma cruzi: inhibitory activity on
      insect cysteine proteinases.
AB  - BACKGROUND: The activity of the major digestive cysteine proteinase detected in
      the intestinal tract of larvae of the bean weevil, Acanthoscelides obtectus
      (Say), was efficiently inhibited by the well-characterized cysteine proteinase
      synthetic inhibitor E-64 and also by a recombinant form of chagasin (r-chagasin),
      a tight-binding cysteine proteinase inhibitor protein from Trypanosoma cruzi.
      RESULTS: Incorporation of r-chagasin into an artificial diet system at 0.1 g kg(
      1) retarded growth rate, decreased larval survival and led to complete mortality
      of A. obtectus at the end of the trial. The observed differences in growth rates
      occurred particularly in the first and second development stages. Artificial
      seeds containing high levels of r-chagasin (0.5-30 g kg(-1)) completely inhibited
      larval penetration. CONCLUSION: Together, the results reported in this paper
      support the hypothesis that the inhibitory activity of r-chagasin towards the
      major insect gut cysteine proteinase in vitro and in vivo is an accurate
      prediction of its insecticidal effects. The selectivity of this inhibitor against
      insect digestive proteinases supports the key role in parasite virulence by
      affecting the endogenous proteinase activity in its natural host.

PMID- 18318461
TI  - Unnatural amino acid incorporation into virus-like particles.
AB  - Virus-like particles composed of hepatitis B virus (HBV) or bacteriophage Qbeta
      capsid proteins have been labeled with azide- or alkyne-containing unnatural
      amino acids by expression in a methionine auxotrophic strain of E. coli. The
      substitution does not affect the ability of the particles to self-assemble into
      icosahedral structures indistinguishable from native forms. The azide and alkyne
      groups were addressed by Cu(I)-catalyzed [3 + 2] cycloaddition: HBV particles
      were decomposed by the formation of more than 120 triazole linkages per capsid in
      a location-dependent manner, whereas Qbeta suffered no such instability. The
      marriage of these well-known techniques of sense-codon reassignment and
      bioorthogonal chemical coupling provides the capability to construct polyvalent
      particles displaying a wide variety of functional groups with near-perfect
      control of spacing.

PMID- 18318462
TI  - Enhanced cell penetration of acid-degradable particles functionalized with cell
      penetrating peptides.
AB  - Biopharmaceuticals, such as proteins and DNA, have demonstrated their potential
      to prevent and cure diseases. The success of such therapeutic agents hinges upon
      their ability to cross complex barriers in the body and reach their target
      intact. In order to reap the full benefits of these therapeutic agents, a
      delivery vehicle capable of delivering cargo to all cell types, both phagocytic
      and non-phagocytic, is needed. This article presents the synthesis and evaluation
      of a microparticle delivery vehicle capable of cell penetration and sub-cellular
      triggered release of an encapsulated payload. pH-sensitive polyacrylamide
      particles functionalized with a polyarginine cell-penetrating peptide (CPP) were
      synthesized. The incorporation of a CPP into the microparticles led to efficient
      uptake by non-phagocytic cells in culture. In addition, the CPP-modified
      particles showed no cytotoxic effects at concentrations used in this study. The
      results suggest that these particles may provide a vehicle for the successful
      delivery of therapeutic agents to various cell types.

PMID- 18318463
TI  - Design, synthesis, and SAR of new pyrrole-oxindole progesterone receptor
      modulators leading to 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1H-indol-5-yl)-1
      methyl-1H-pyrrole-2-carbonitrile (WAY-255348).
AB  - We have continued to explore the 3,3-dialkyl-5-aryloxindole series of
      progesterone receptor (PR) modulators looking for new agents to be used in female
      healthcare: contraception, fibroids, endometriosis, and certain breast cancers.
      Previously we reported that subtle structural changes with this and related
      templates produced functional switches between agonist and antagonist properties
      ( Fensome et al. Biorg. Med. Chem. Lett. 2002, 12, 3487; 2003, 13, 1317 ). We
      herein report a new functional switch within the 5-(2-oxoindolin-5-yl)-1 H
      pyrrole-2-carbonitrile class of compounds. We found that the size of the 3,3
      dialkyl substituent is important for controlling the functional response; thus
      small groups (dimethyl) afford potent PR antagonists, whereas larger groups
      (spirocyclohexyl) are PR agonists. The product from our optimization activities
      in cell-based systems and also for kinetic properties in rodents and nonhuman
      primates was 5-(7-fluoro-3,3-dimethyl-2-oxo-2,3-dihydro-1 H-indol-5-yl)-1-methyl
      1 H-pyrrole-2-carbonitrile 27 (WAY-255348), which demonstrated potent and robust
      activity on PR antagonist and contraceptive end points in the rat and also in
      cynomolgus and rhesus monkeys including ovulation inhibition, menses induction,
      and reproductive tract morphology.

PMID- 18318464
TI  - Assessment of drug-lipid complex formation by a high-throughput Langmuir-balance
      and correlation to phospholipidosis.
AB  - Phospholipidosis, the accumulation of phospholipids in cells, is a relatively
      frequent side effect of cationic amphiphilic drugs. In response to the industry
      need, several methods have been recently published for the prediction of the
      phospholipidosis-inducing potential of drug candidates. We describe here a high
      throughput physicochemical approach, which is based on the measurement of drug
      phospholipid complex formation observed by their effect on the critical micelle
      concentration (CMC) of a short-chain acidic phospholipid. The relative change due
      to the drug, CMC(DL)/CMC(L) provides a direct measure of the energy of the drug
      phospholipid association, irrespective of the nature of the interaction.
      Comparison of results for 53 drugs to human data, animal testing, cell culture
      assays, and other screening methods reveals very good correlation to their
      phospholipidosis-inducing potential. The method is well suited for screening
      already in early phases of drug discovery.

PMID- 18318465
TI  - Benzyl ether-linked glucuronide derivative of 10-hydroxycamptothecin designed for
      selective camptothecin-based anticancer therapy.
AB  - A beta-glucuronidase-activated prodrug approach was applied to 10
      hydroxycamptothecin, a Camptotheca alkaloid with promising antitumor activity but
      poor water solubility. We synthesized a glucuronide prodrug of 10
      hydroxycamptothecin ( 7) in which glucuronic acid is connected via a self
      immolative 3-nitrobenzyl ether linker to the 10-OH group of 10
      hydroxycamptothecin. Compound 7 was 80 times more soluble than 10
      hydroxycamptothecin in aqueous solution at pH 4.0 and was stable in human plasma.
      Prodrug 7 was 10- to 15-fold less toxic than the parent drug to four human tumor
      cell lines. In the presence of beta-glucuronidase, prodrug 7 could be activated
      to elicit similar cytotoxicity to the parent drug in tumor cells. Enzyme kinetic
      studies showed that Escherichia coli beta-glucuronidase had a quite low K m of
      0.18 microM for compound 7 and exhibited 520 times higher catalytic efficiency
      for 7 than for 6 (a glucuronide prodrug of 9-aminocamptothecin). Molecular
      modeling studies predicted that compound 7 would have a higher binding affinity
      to human beta-glucuronidase than compound 6. Prodrug 7 may be useful for
      selective cancer chemotherapy by a prodrug monotherapy (PMT) or antibody-directed
      enzyme prodrug therapy (ADEPT) strategy.

PMID- 18318466
TI  - Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent
      naphthoquinone-based inhibitors.
AB  - Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic
      target for the treatment of cancer, chronic viral infections, and other diseases
      characterized by pathological immune suppression. While small molecule inhibitors
      of IDO exist, there remains a dearth of high-potency compounds offering in vivo
      efficacy and clinical translational potential. In this study, we address this gap
      by defining a new class of naphthoquinone-based IDO inhibitors exemplified by the
      natural product menadione, which is shown in mouse tumor models to have similar
      antitumor activity to previously characterized IDO inhibitors. Genetic validation
      that IDO is the critical in vivo target is demonstrated using IDO-null mice.
      Elaboration of menadione to a pyranonaphthoquinone has yielded low nanomolar
      potency inhibitors, including new compounds which are the most potent reported to
      date (K(i) = 61-70 nM). Synthetic accessibility of this class will facilitate
      preclinical chemical-genetic studies as well as further optimization of
      pharmacological parameters for clinical translation.

PMID- 18318467
TI  - Arginine binding motifs: design and synthesis of galactose-derived arginine
      tweezers as galectin-3 inhibitors.
AB  - Anionic O2 derivatives of methyl 3-deoxy-3-(4-methylbenzamido)-1-thio-beta-D
      galactopyranoside have been synthesized as inhibitors against galectin-3. The
      sulfate, H-phosphonate, and benzyl phosphate derivatives showed an increased
      affinity as compared to the parent unsubstituted galactopyranoside. Modeling
      revealed arginine-144 being pinched by the C3 benzamide and O2 anionic
      substituents in that the benzamide stacked face-to-face and the anionic O2
      substituent ion-paired with the guanidinium moiety.

PMID- 18318468
TI  - Design, synthesis, and biological evaluation of AT1 angiotensin II receptor
      antagonists based on the pyrazolo[3,4-b]pyridine and related heteroaromatic
      bicyclic systems.
AB  - Novel AT 1 receptor antagonists bearing the pyrazolo[3,4- b]pyridine bicyclic
      heteroaromatic system (or structurally related moieties) were designed and
      synthesized as the final step of a large program devoted to the development of
      new antihypertensive agents and to the understanding of the molecular basis of
      their pharmacodynamic and pharmacokinetic properties. The preliminary
      pharmacological characterization revealed nanomolar AT 1 receptor affinity for
      several compounds of the series and a potent antagonistic activity in isolated
      rabbit aortic strip functional assay for 7c and 8a. These results stimulated the
      study of the biopharmaceutical properties of some selected compounds, which were
      found to be characterized by a permeability from medium to high. Remarkably, the
      least permeable 7c showed both permeability and oral bioavailability (80%) higher
      than losartan, but its terminal half-life was shorter. These results suggest that
      the permeability is not a limiting factor in the pharmacokinetics of these AT 1
      receptor antagonists.

PMID- 18318469
TI  - Discovery of a new class of potent, selective, and orally bioavailable CRTH2
      (DP2) receptor antagonists for the treatment of allergic inflammatory diseases.
AB  - A novel chemical class of potent chemoattractant receptor-homologous expressed on
      Th2 lymphocytes (CRTH2 or DP2) antagonists is reported. An initial and moderately
      potent spiro-indolinone compound ( 5) was found during a high-throughput
      screening campaign. Structure-activity relationship (SAR) investigation around
      the carboxylic acid group revealed that changes in this part of the molecule
      could lead to a reversal of functional activity, yielding weakly potent agonists.
      SAR investigation of the succinimide functional group led to the discovery of
      several single-digit nanomolar antagonists. The potency of these compounds was
      confirmed in a human eosinophil chemotaxis assay. Moreover, compounds ( R)- 58
      and ( R)- 71 were shown to possess pharmacokinetic properties suitable for
      development as an orally bioavailable drug.

PMID- 18318470
TI  - X-ray snapshot of the mechanism of inactivation of human neutrophil elastase by
      1,2,5-thiadiazolidin-3-one 1,1-dioxide derivatives.
AB  - The mechanism of action of a general class of mechanism-based inhibitors of
      serine proteases, including human neutrophil elastase (HNE), has been elucidated
      by determining the X-ray crystal structure of an enzyme-inhibitor complex. The
      captured intermediate indicates that processing of inhibitor by the enzyme
      generates an N-sulfonyl imine functionality that is tethered to Ser195, in
      accordance with the postulated mechanism of action of this class of inhibitors.
      The identity of the HNE-N-sulfonyl imine species was further corroborated using
      electrospray ionization mass spectrometry.

PMID- 18318471
TI  - Covalent grafting of common trihydroxymethylaminomethane in the headgroup region
      imparts high serum compatibility and mouse lung transfection property to cationic
      amphiphile.
AB  - Clinical success of cationic transfection lipids in nonviral gene therapy
      continues to remain critically dependent on the use of serum compatible cationic
      amphiphiles efficient in delivering genes into our body cells. To this end, we
      demonstrate that covalent grafting of simple Tris-base component of the widely
      used biological Tris buffer in the headgroup region is capable of imparting high
      serum compatibility and intravenous mouse lung transfection properties to
      cationic amphiphile.

PMID- 18318473
TI  - Support-vector-machine-based ranking significantly improves the effectiveness of
      similarity searching using 2D fingerprints and multiple reference compounds.
AB  - Similarity searching using molecular fingerprints is computationally efficient
      and a surprisingly effective virtual screening tool. In this study, we have
      compared ranking methods for similarity searching using multiple active reference
      molecules. Different 2D fingerprints were used as search tools and also as
      descriptors for a support vector machine (SVM) algorithm. In systematic database
      search calculations, a SVM-based ranking scheme consistently outperformed nearest
      neighbor and centroid approaches, regardless of the fingerprints that were
      tested, even if only very small training sets were used for SVM learning. The
      superiority of SVM-based ranking over conventional fingerprint methods is
      ascribed to the fact that SVM makes use of information about database molecules,
      in addition to known active compounds, during the learning phase.

PMID- 18318472
TI  - Novel breast cancer biomarkers identified by integrative proteomic and gene
      expression mapping.
AB  - Proteomic and transcriptomic platforms both play important roles in cancer
      research, with differing strengths and limitations. Here, we describe a proteo
      transcriptomic integrative strategy for discovering novel cancer biomarkers,
      combining the direct visualization of differentially expressed proteins with the
      high-throughput scale of gene expression profiling. Using breast cancer as a case
      example, we generated comprehensive two-dimensional electrophoresis (2DE)/mass
      spectrometry (MS) proteomic maps of cancer (MCF-7 and HCC-38) and control (CCD
      1059Sk) cell lines, identifying 1724 expressed protein spots representing 484
      different protein species. The differentially expressed cell-line proteins were
      then mapped to mRNA transcript databases of cancer cell lines and primary breast
      tumors to identify candidate biomarkers that were concordantly expressed at the
      gene expression level. Of the top nine selected biomarker candidates, we
      reidentified ANX1, a protein previously reported to be differentially expressed
      in breast cancers and normal tissues, and validated three other novel candidates,
      CRAB, 6PGL, and CAZ2, as differentially expressed proteins by
      immunohistochemistry on breast tissue microarrays. In total, close to half (4/9)
      of our protein biomarker candidates were successfully validated. Our study thus
      illustrates how the systematic integration of proteomic and transcriptomic data
      from both cell line and primary tissue samples can prove advantageous for
      accelerating cancer biomarker discovery.

PMID- 18318474
TI  - Structure-based virtual screening with supervised consensus scoring: evaluation
      of pose prediction and enrichment factors.
AB  - Since the evaluation of ligand conformations is a crucial aspect of structure
      based virtual screening, scoring functions play significant roles in it. However,
      it is known that a scoring function does not always work well for all target
      proteins. When one cannot know which scoring function works best against a target
      protein a priori, there is no standard scoring method to know it even if 3D
      structure of a target protein-ligand complex is available. Therefore, development
      of the method to achieve high enrichments from given scoring functions and 3D
      structure of protein-ligand complex is a crucial and challenging task. To address
      this problem, we applied SCS (supervised consensus scoring), which employs a
      rough linear correlation between the binding free energy and the root-mean-square
      deviation (rmsd) of a native ligand conformations and incorporates protein-ligand
      binding process with docked ligand conformations using supervised learning, to
      virtual screening. We evaluated both the docking poses and enrichments of SCS and
      five scoring functions (F-Score, G-Score, D-Score, ChemScore, and PMF) for three
      different target proteins: thymidine kinase (TK), thrombin (thrombin), and
      peroxisome proliferator-activated receptor gamma (PPARgamma). Our enrichment
      studies show that SCS is competitive or superior to a best single scoring
      function at the top ranks of screened database. We found that the enrichments of
      SCS could be limited by a best scoring function, because SCS is obtained on the
      basis of the five individual scoring functions. Therefore, it is concluded that
      SCS works very successfully from our results. Moreover, from docking pose
      analysis, we revealed the connection between enrichment and average centroid
      distance of top-scored docking poses. Since SCS requires only one 3D structure of
      protein-ligand complex, SCS will be useful for identifying new ligands.

PMID- 18318475
TI  - Migratory insertion of the R2P group into a nitrogen-nitrogen bond - a novel type
      of rearrangement in phosphorus-nitrogen ligand chemistry. 3. The rearrangement of
      triphosphinohydrazide ligand -N(PPh2)-N(PPh2)2 to triphosphazenide anion {[(Ph2P
      N]2PPh2}- in the coordination sphere of divalent cobalt and nickel.
AB  - Hydrazine dihydrochloride reacts with 3 equiv of Ph2PCl in tetrahydrofuran in the
      presence of triethylamine to give tris(diphenylphosphino)hydrazine (1) in 70%
      yield. Each nitrogen atom in 1 has a trigonal-planar environment according to X
      ray analysis. Thermolysis of 1 at 130 degrees C results in the formation of two
      products: bis(diphenylphosphino)amine and octaphenylcyclotetraphosphazene. The
      interaction of free ligand 1 with NiBr2 affords a simple adduct [(Ph2P)2N-NH
      PPh2]NiBr2, while its anionic (hydrazide) form undergoes rearrangement in a
      coordination sphere of divalent cobalt and nickel involving migratory insertion
      of the Ph2P group into a nitrogen-nitrogen bond. The reaction of 1 with cobalt
      bis(trimethylsilyl)amide, [(Me3Si)2N]2Co, yields the complex of phosphazenide
      type (Me3Si)2N-Co[(Ph2PN)2PPh2] (2) in 86% yield. A similar reaction of 1 with
      nikelocene proceeds with substitution of one Cp ring to form durable 18-electron
      complex CpNi[(Ph2PN)2PPh2] (3).

PMID- 18318476
TI  - Computational study of the factors controlling enantioselectivity in
      ruthenium(II) hydrogenation catalysts.
AB  - The reduction of prochiral ketones catalyzed by Ru(diphosphine)(diamine)
      complexes has been studied at the DFT-PBE level of theory. Calculations have been
      conducted on real size systems [trans-Ru(H)2(S, S-dpen)(S-xylbinap) +
      acetophenone], [trans-Ru(H)2(S, S-dpen)(S-tolbinap) + acetophenone] and [trans
      Ru(H)2(S, S-dpen)(S-xylbinap) + cyclohexyl methyl ketone] with the aim of
      identifying the factors controlling the enantioselectivity in
      Ru(diphosphine)(diamine) catalysts. The high enantiomeric excess (99%) in the
      hydrogenation of acetophenone catalyzed by trans-Ru(H)2(S, S-dpen)(S-xylbinap)
      has been explained in terms of the existence of a stable intermediate along the
      reaction pathway associated with the (R)-alcohol. The formation of this
      intermediate is hindered with the competitive pathways, which consequently
      increases the activation energy for the hydrogen transfer acetophenone/(S)
      phenylethanol reaction. For the [trans-Ru(H)2(S, S-dpen)(S-tolbinap) +
      acetophenone] system, the lower enantioselectivity (i.e. 80%) is rationalized by
      the smaller differences in the activation energy between the competitive pathways
      which differentiate between the two diastereomeric approaches of the prochiral
      ketone. The DFT-PBE results suggest that this reaction is driven to the (R)
      product only by the process of binding the acetophenone to the active site of the
      trans-Ru(H) 2(S, S-dpen)(S-tolbinap) catalyst. For the hydrogenation of
      cyclohexyl methyl ketone catalyzed by trans-Ru(H)2(S, S-dpen)(S-xylbinap), the
      low performance in the enantioselective hydrogenation of the dialkyl ketone (i.e.
      37%) is again explained by the small differences in the activation and binding
      energies which are the factors which could effectively differentiate between the
      two alkyl groups.

PMID- 18318477
TI  - Anion recognition of chloride and bromide by a rigid dicobalt(II) cryptate.
AB  - The crystal structures of [Co 2L(Cl)](ClO 4) 3 ( 1), [Co 2L(Br)](ClO 4) 3 ( 2),
      [Co 2L(OH)(OH 2)]I 3 ( 3), and [Co 2L (1)(Cl)](ClO 4) 3 ( 4), the density
      functional theory calculations, as well as the binding constants of [Co 2L] (4+)
      toward Cl (-) and Br (-) and of [Co 2L (1)] (4+) toward Cl (-), are reported in
      this paper (L = N[(CH 2) 2NHCH 2(C 6H 4- p)CH 2NH(CH 2) 2] 3N, L (1) = N[(CH 2)
      2NHCH 2(C 6H 4- m)CH 2NH(CH 2) 2] 3N). The rigid dicobalt(II) cryptate [Co 2L]
      (4+) shows the recognition of Cl (-) and Br (-) but not of F (-) and I (-),
      because of the size matching to its rigid cavity. We also found that the relative
      rigid tripodal skeleton of L than that of L (1) results in the higher affinity of
      [Co 2L] (4+) toward Cl (-). Magnetic susceptibility measurements of 1 and 2
      indicate that the two Co(II) atoms in the cryptates are antiferromagnetically
      coupled through the Cl (-)/Br (-) bridge, with g = 2.19, J = -13.7 cm (-1) for 1,
      and g = 2.22, J = -17.1 cm (-1) for 2.

PMID- 18318478
TI  - Characterization and properties of novel infrared nonlinear optical crystal
      CsGe(BrxCl1-x)3.
AB  - Innovative infrared nonlinear optical crystals CsGe(BrxCl(1-x))3 were
      synthesized. Their powder X-ray diffraction patterns indicated that they had
      rhombohedral structures with (R3m, No. 160) space group symmetry. Their
      structural distortion increased with x. The Kurtz powder techniques revealed that
      the nonlinear optical efficiency of CsGeBr3 is about 9.64 times larger than that
      of rhombohedral CsGeCl3 and 28.29 times larger than that of KH2PO4 (KDP); most
      importantly, CsGe(BrxCl(1-x))3 is phase-matchable. The transparent infrared
      spectrum of rhombohedral CsGe(BrxCl(1-x))3 was extended to over 30 mum and
      demonstrated its potential in the field of nonlinear optics and applicability in
      the infrared region.

PMID- 18318479
TI  - 3D coordination networks based on supramolecular chains as building units:
      synthesis and crystal structures of two silver(I) pyridyldiethynides.
AB  - Two silver(I) pyridyldiethynides, [Ag2(3,5-C2PyC2).4CF3CO2Ag.4H2O] ( A) and [Ag
      2(3,5-C2PyC2).3AgNO3.H2O](B), were synthesized by reactions of 3,5
      diethynylpyridine with silver trifluoroacetate and silver nitrate in high yield,
      respectively. X-ray crystallographic studies revealed that in A pyridyldiethynide
      groups connect Ag 11 cluster units to generate 1D supramolecular chains as
      bridging ligands, where each ethynide group interacts with four silver atoms.
      These supramolecular chains bearing pyridyl groups are linked by silver ions to
      form wavelike layers, which are further connected by trifluoroacetate ligands to
      afford a 3D coordination network. However, B exhibits a different structural
      feature, where two ethynide groups in one pyridyldiethynide ligand coordinate to
      three and four silver atoms, respectively. These silver ethynide cluster units
      are linked through silver-ethynide and argentophilic interactions, leading to a
      double silver chain by sharing silver atoms in these units. In B, the silver
      double chains are further connected by bridging pyridyldiethynide groups to
      generate 2D networks, which interact through the Ag-N coordination bonds between
      silver atoms and pyridyl groups in the adjacent layers to generate a 3D
      coordination network. In these two compounds, trifluoroacetate and nitrate groups
      exhibit different bonding modes, indicating that the counterion is an important
      factor influencing the structures of supramolecular chains and coordination
      networks.

PMID- 18318480
TI  - Molecular architectures for trimetallic d/f/d complexes: magnetic studies of a
      LnCu2 core.
AB  - Five new trinuclear Cu-Ln-Cu cluster complexes have been prepared by a one-pot
      reaction using H3bcn (tris- N,N',N''-(2-hydroxybenzyl)-1,4,7-triazacyclononane)
      and Ln = La(III), Nd(III), Gd(III), Dy(III), and Yb(III) where the d- and f-block
      metal ions are in close proximity desirable for magnetic studies. The
      [LnCu2(bcn)2]ClO4.nH2O complexes possess the same stoichiometry as the previously
      reported [LnNi2(bcn)2]ClO4.nH2O and [LnZn2(bcn)2]ClO4.nH2O systems. Additionally,
      the solid state structures of the LnCu2 complexes appear to be isostructural to
      the LnNi2 and LnZn2 species as determined by their nearly superimposable IR
      spectra. The similarities in the structures of the [LnTM2(bcn)2]ClO4.nH2O series,
      where TM = Zn(II), Ni(II), and Cu(II), allow for direct comparison of their
      magnetic exchange. An empirical approach, removing first-order anisotropic
      contributions determined from the analogous [LnZn2(bcn)2]ClO4.nH2O was used to
      study the d/f/d spin interactions in the [LnCu2(bcn)2]ClO4.nH2O complexes. A
      ferromagnetic exchange was determined where Ln = Gd(III), Dy(III), or Yb(III) and
      an antiferromagnetic exchange for Ln = Nd(III), identical to the magnetic
      exchange observed for the [LnNi2(bcn)2]ClO4.nH2O complexes. An exchange integral
      of 3.67 cm(-1) for the trimetallic [GdCu2(bcn)2]ClO4.3H2O species was determined
      using a modified spin Hamiltonian. The [Cu(Hbcn)] and the [Cu3(Hbcn)2](ClO4)2
      building blocks of the larger coaggregated d/f/d species were also synthesized,
      and their structures are reported.

PMID- 18318481
TI  - Molecular architectures for trimetallic d/f/d complexes: structural and magnetic
      properties of a LnNi2 core.
AB  - A series of cationic, trimetallic d/f/d complexes have been prepared which use a
      multidentate, macrocyclic amine phenol ligand to coordinate divalent first row d
      block transition metal ions (TM) and lanthanides (Ln) ions in close proximity,
      desirable for magnetic studies. Isolable complexes of the d/f/d cluster compounds
      with the formula [Ln(TM)2(bcn)2]ClO4.nH2O, where H3bcn is tris-N, N', N''-(2
      hydroxybenzyl)-1,4,7-triazacyclononane, TM = Zn(II) and Ni(II) and Ln = La(III),
      Nd(III), Gd(III), Dy(III), and Yb(III), were synthesized by a one-pot sequential
      reaction of stoichiometric amounts of H 3bcn with the TM(II) and Ln(III) metal
      ions. The spontaneously formed cationic complexes were characterized by a variety
      of analytical techniques including IR, NMR, +ESI-MS, and EA. The [TM(Hbcn)].nH2O
      and [TM3(bcn)2].nH2O complexes were also synthesized to probe the building blocks
      of the d/f/d coaggregated species. The solid-state X-ray crystal structures of
      [GdNi2(bcn)2(CH3CN)2]ClO4.CH3CN and [GdZn2(bcn)2(CH3CN)2]ClO4.CH3CN were
      determined to be nearly identical with each TM(II) encapsulated in an octahedral
      geometry by the N3O3 binding pocket of the bcn (3-) ligand. The eight coordinate
      Gd(III) was bicapped by two [TM(bcn)](-) moieties and coordinated by two solvent
      molecules. Because of the isostructurality of the [LnZn2(bcn)2]ClO4.nH2O and
      [LnNi2(bcn)2]ClO4.nH2O complexes, an empirical approach using the LnZn2 magnetic
      data was utilized to remove first-order anisotropic contributions from the LnNi2
      species. Ferromagnetic spin interactions were determined for the
      [LnNi2(bcn)2]ClO4.nH2O complexes, where Ln = Gd(III), Dy(III), and Yb(III), while
      an antiferromagnetic exchange was observed for Ln = Nd(III).

PMID- 18318482
TI  - Imidazole-substituted oxoverdazyl radical as a mediator of intramolecular and
      intermolecular exchange interaction.
AB  - The 3-(2'-imidazolyl)-1,5-dimethyl-6-oxoverdazyl radical (imvd(*)) and the
      corresponding tetrazane H3imvd were prepared and structurally characterized, the
      former as two different hydrates. Reaction of imvd(*) with [M(hfac)2] led to the
      formation of monometallic complexes [M(hfac)2(imvd(*))] (M = Ni and Mn). They
      were characterized by single-crystal X-ray diffraction. In the solid state, all
      four radical-containing compounds exhibit imidazole-oxoverdazyl pi stacking.
      Following the structural analysis, imvd(*) behaves as an antiferromagnetic (AF)
      coupled chain with J = -100 cm(-1) (H = -J summation operator SiS(i+1)). The
      magnetic behavior of [M(hfac)2(imvd(*))] complexes is interpreted with a four
      coupled spin model with a metal ion radical intramolecular interaction (JMn = 
      62.5 cm(-1) and JNi = 193 cm(-1); H = -JSMSimvd) and an AF intermolecular
      interaction (JMn' = -12.6 cm(-1) and JNi' = -4.3 cm(-1)) related to imidazole
      oxoverdazyl pi stacking.

PMID- 18318483
TI  - New approach to the synthesis of an organopolymolybdate polymer in aqueous media
      by linkage of multicarboxylic ligands.
AB  - The reaction of molybdates with multicarboxylic ligands resulted in the
      crystalline materials of [Na 8(Mo (VI) 10O 32EDTA)(H 2O) 35] n ( 1) and (NH 4) 8
      n [Mo (VI) 10O 32PDTA] n (H 2O) 30 n ( 2) (EDTA = 1,2-diaminoethanetetraacetate;
      PDTA = 1,3-diaminopropanetetraacetate). In the two compounds, decamolybdate
      clusters are covalently linked by multicarboxylic ligands to form unusual meso
      helical chains. For the first time, the synthesis of an organopolyoxometalate
      polymer is realized in aqueous media, which opens a green chemical approach to
      the fabrication of polyoxometalate-based polymers. The photochromic properties of
      1 in the poly(vinyl alcohol) film displayed reddish-brown coloration upon UV
      irradiation, providing a new coloration material for photochromic films.

PMID- 18318484
TI  - La6Br10Fe: a La6Fe octahedron with a mixed M6X12/M6X8 type environment.
AB  - The title compound was synthesized from La, LaBr3, and Fe under Ar atmosphere at
      800 degrees C. It crystallizes in space group P4(1) (No. 76) with lattice
      constants a = 8.255(1) A and c = 30.033(6) A. The structure features an isolated
      Fe-centered La 6 octahedron with all corners, 9 of its 12 edges, and 3 of its 8
      triangular faces coordinated, bridged, or capped by Br atoms. The La6Fe
      octahedron is significantly distorted, and the La coordination by Br atoms
      deviates from the common close-packing arrangements found in other reduced rare
      earth metal halides. Band structure, bonding, and physical properties of the
      compound have been investigated.

PMID- 18318485
TI  - Nickel and cobalt hexamethylentetramine complexes (NO3)2Me(H2O)6(HMTA)2.4H2O (Me
      = Co2+, Ni2+): new molecular precursors for the preparation of metal dispersions.
AB  - Nickel and cobalt hexamethylenetetramine (HMTA) complexes
      (NO3)2Me(H2O)6(HMTA)2.4H2O were prepared and characterized structurally by single
      crystal X-ray diffraction. Both compounds crystallize in the triclinic P1 space
      group with the same structure. The structures are three-dimensional hydrogen
      bonded supramolecular frameworks containing two-dimensional cationic assemblies
      connected with proton acceptors, which are noncoordinated anionic species
      (nitrate) and neutral HMTA molecules. Thermal decomposition of these compounds
      under an inert atmosphere leads to the high-surface-area metal-carbon foams
      containing nickel and cobalt nanoparticles embedded within onionlike carbon
      shells. The decomposition process as studied by thermal analysis and in situ X
      ray absorption spectroscopy (XAS) measurements occurs as a rapid loss of oxygen
      in the form of CO, beginning at temperatures as low as 323 K. As the in situ XAS
      study demonstrated, the evolution of nickel and cobalt coordination spheres
      occurs with intermediate formation of amorphous metal carbides, which
      subsequently decompose to the metal nanoparticles covered with carbon shells.

PMID- 18318486
TI  - Investigations of acidity and nucleophilicity of diphenyldithiophosphinate
      ligands using theory and gas-phase dissociation reactions.
AB  - Diphenyldithiophosphinate (DTP) ligands modified with electron-withdrawing
      trifluoromethyl (TFM) substitutents are of high interest because they have
      demonstrated potential for exceptional separation of Am (3+) from lanthanide (3+)
      cations. Specifically, the bis( ortho-TFM) (L 1 (-)) and ( ortho-TFM)( meta-TFM)
      (L 2 (-)) derivatives have shown excellent separation selectivity, while the bis(
      meta-TFM) (L 3 (-)) and unmodified DTP (L u (-)) did not. Factors responsible for
      selective coordination have been investigated using density functional theory
      (DFT) calculations in concert with competitive dissociation reactions in the gas
      phase. To evaluate the role of (DTP + H) acidity, density functional calculations
      were used to predict p K a values of the free acids (HL n ), which followed the
      trend of HL 3 < HL 2 < HL 1 < HL u. The order of p K a for the TFM-modified
      (DTP+H) acids was opposite of what would be expected based on the e (-)
      withdrawing effects of the TFM group, suggesting that secondary factors influence
      the p K a and nucleophilicity. The relative nucleophilicities of the DTP anions
      were evaluated by forming metal-mixed ligand complexes in a trapped ion mass
      spectrometer and then fragmenting them using competitive collision induced
      dissociation. On the basis of these experiments, the unmodified L u (-) anion was
      the strongest nucleophile. Comparing the TFM derivatives, the bis( ortho-TFM)
      derivative L 1 (-) was found to be the strongest nucleophile, while the bis( meta
      TFM) L 3 (-) was the weakest, a trend consistent with the p K a calculations. DFT
      modeling of the Na (+) complexes suggested that the elevated cation affinity of
      the L 1 (-) and L 2 (-) anions was due to donation of electron density from
      fluorine atoms to the metal center, which was occurring in rotational conformers
      where the TFM moiety was proximate to the Na (+)-dithiophosphinate group.
      Competitive dissociation experiments were performed with the dithiophosphinate
      anions complexed with europium nitrate species; ionic dissociation of these
      complexes always generated the TFM-modified dithiophosphinate anions as the
      product ion, showing again that the unmodified L u (-) was the strongest
      nucleophile. The Eu(III) nitrate complexes also underwent redox elimination of
      radical ligands; the tendency of the ligands to undergo oxidation and be
      eliminated as neutral radicals followed the same trend as the nucleophilicities
      for Na (+), viz. L 3 (-) < L 2 (-) < L 1 (-) < L u (-).

PMID- 18318487
TI  - Fabrication of hierarchical ZnO architectures and their superhydrophobic surfaces
      with strong adhesive force.
AB  - Grid-structured ZnO microsphere arrays assembled by uniform ZnO nanorods were
      fabricated by noncatalytic chemical vapor deposition, taking advantage of
      morphologies of alumina nanowire pyramid substrates and ZnO oriented growth
      habits. Every ZnO microsphere (similar to the micropapilla on a lotus leaf
      surface) is assembled by over 200 various oriented ZnO nanorods (similar to the
      hairlike nanostructures on mircopapilla of a lotus leaf). This lotus-leaf-like
      ZnO micro-nanostructure films reveal superhydrophobicity and ultrastrong adhesive
      force to liquid. The realization of this hierarchical ZnO nanostructure film
      could be important for further understanding wettability of biological surfaces
      with micro-nanostructure and application in microfluidic devices.

PMID- 18318488
TI  - Structural, photophysical, and catalytic properties of Au(I) complexes with 4
      substituted pyridines.
AB  - Ionic gold(I) complexes with general formula of [Au(Py)2][AuCl2] and
      [Au(Py)2][PF6] (Py = 4-substituted pyridines) have been synthesized. Structures
      of five Au(I) complexes and a Ag(I) complex were determined by single crystal X
      ray diffraction. Evidence for cationic aggregation of [Au(py)2][PF6] complexes in
      solution was obtained by conductivity measurements and by the isosbestic point
      observed from variable temperature UV-visible absorption spectra. All compounds
      were luminous in the solid state. Calculations employing density functional
      theory were performed to shed light on the nature of the electronic transitions.
      While the [Au(4-dmapy)2][AuCl2] (4-dmapy = 4-dimethylaminopyridine) and [Au(4
      pic)2][AuCl2] (4-pic = 4-picoline) emissions were found to be mainly ligand in
      nature, their [PF6](-) counterparts involved a Au...Au-interaction imbedded in
      the highest occupied molecular orbital. [Au(4-dmapy)2][AuCl2] was found to be an
      efficient catalyst for Suzuki cross-coupling of aryl bromide and phenylboronic
      acid.

PMID- 18318489
TI  - {[P(o-tolyl)3]Br}2[Cu2Br6](Br2)--an ionic compound containing molecular bromine.
AB  - Dark green cuboid-shaped crystals of the composition {[P(o-tolyl) 3]Br} 2[Cu 2Br
      6](Br 2) are obtained by the reaction of P(o-tolyl) 3 and CuBr 2 with Br 2 in the
      ionic liquid [NMeBu 3][N(Tf) 2]. The bromocuprate crystallizes triclinic [space
      group P1; Z = 1; a = 10.667(2) A; b = 10.695(2) A; c = 11.582(2) A; alpha =
      74.42(3) degrees ; beta = 75.64(3) degrees ; and gamma = 85.68(3) degrees ]. The
      title compound is constituted of {[P(o-tolyl) 3]Br} (+) cations and [Cu 2Br 6] (2
      ) anions and contains molecular dibromine [d Br-Br = 2.341(1) A]. The latter is
      verified by thermogravimetry and mass spectrometry.

PMID- 18318490
TI  - High-pressure studies of (Mg0.9Fe0.1)2SiO4 olivine using raman spectroscopy, X
      ray diffraction, and mossbauer spectroscopy.
AB  - High-pressure studies of (Mg(0.9)Fe(0.1))2SiO4 olivine were performed at ambient
      temperature using X-ray diffraction, Raman spectroscopy, and Mossbauer
      spectroscopy. At approximately 40 GPa, a change of compressibility associated
      with saturation of the anisotropic compression mechanism was detected. This
      change is interpreted to result from the appearance of Si2O7 dimer defects, as
      deduced from Raman spectroscopy; the appearance of such defects also accounts for
      the previously reported pressure-induced amorphization observed for this material
      upon additional compression. Furthermore, this behavior is followed by a spin
      crossover of Fe(2+) that occurs over a wide pressure range, as revealed by
      Mossbauer spectroscopy.

PMID- 18318491
TI  - Distinct and long-lived activity states of single enzyme molecules.
AB  - Individual enzyme molecules have been observed to possess discrete and different
      turnover rates due to the presence of long-lived activity states. These stable
      activity states are thought to result from different molecular conformations or
      post-translational modifications. The distributions in kinetic activity observed
      in previous studies were obtained from small numbers of single enzyme molecules.
      Due to this limitation, it has not been possible to fully characterize the
      different kinetic and equilibrium binding parameters of single enzyme molecules.
      In this paper, we analyze hundreds of single beta-galactosidase molecules
      simultaneously; using a high-density array of 50,000 fL-reaction chambers, we
      confirm the presence of long-lived kinetic states within a population of enzyme
      molecules. Our analysis has isolated the source of kinetic variability to kcat.
      The results explain the kinetic variability within enzyme molecule populations
      and offer a deeper understanding of the unique properties of single enzyme
      molecules. Gaining a more fundamental understanding of how individual enzyme
      molecules work within a population should provide insight into how they affect
      downstream biochemical processes. If the results reported here can be generalized
      to other enzymes, then the stochastic nature of individual enzyme molecule
      kinetics should have a substantial impact on the overall metabolic activity
      within a cell.

PMID- 18318492
TI  - Methylmercury accumulation in rice (Oryza sativa L.) grown at abandoned mercury
      mines in Guizhou, China.
AB  - Mercury is a global pollutant that can transform into methylmercury, a highly
      toxic and bioaccumulative organic form. Previous surveys have shown that fish is
      the main source of human methylmercury exposure, whereas most other food products
      have an average value below 20 microg/kg and primarily in the inorganic form.
      This paper reports that methylmercury in rice (Oryza sativa L.) grown at
      abandoned mercury mining areas contained levels >100 microg/kg in its edible
      portion and proved to be 10-100 times higher than other crop plants. The daily
      adult intake of methylmercury through rice consumption causes abnormally high
      methylmercury exposure to humans. The results demonstrate that rice is a
      methylmercury bioaccumulative plant and the main methylmercury source for human
      exposure in the areas studied.

PMID- 18318493
TI  - Evidence of the formation of light polycyclic aromatic hydrocarbons during the
      oxidation of edible oils in closed containers at room temperature.
AB  - Solid phase microextraction (SPME) followed by gas chromatography-mass
      spectrometry (GC-MS) of the headspace composition of two sunflower oil samples
      was carried out; both samples were taken from the same original oil, stored for a
      prolonged time (112 months) in closed containers at room temperature under
      different air/oil volume ratios. Great differences in the headspace compositions
      of both samples were found due to the different oxidation levels reached. One of
      the most significant findings is that both contain monocyclic and light
      polycyclic aromatic hydrocarbons, the proportions of which are in line with the
      oxidation level of the sample. The determination of polycyclic aromatic compounds
      in the oil liquid matrix of both oil samples, carried out by means of a classical
      scheme of isolation, cleanup, separation, and quantification, showed that the
      concentrations of these compounds in the oil liquid phase also follow the
      oxidation degree reached by each sample, proving that this oxidation process at
      room temperature leads to the formation of these compounds.

PMID- 18318494
TI  - Compositional analysis and rheological properties of gum kondagogu (Cochlospermum
      gossypium): a tree gum from India.
AB  - Gum kondagogu ( Cochlospermum gossypium) is a tree exudate gum that belongs to
      the family Bixaceae. Compositional analysis of the gum by HPLC and LC-MS revealed
      uronic acids to be the major component of the polymer ( approximately 26 mol %).
      Furthermore, analysis of the gum by GC-MS indicated the presence of sugars such
      as arabinose (2.52 mol %), mannose (8.30 mol %), alpha- d-glucose (2.48 mol %),
      beta- d-glucose (2.52 mol %), rhamnose (12.85 mol %), galactose (18.95 mol %), d
      glucuronic acid (19.26 mol %), beta- d-galactouronic acid (13.22 mol %), and
      alpha- d-galacturonic acid (11.22 mol %). Gum kondagogu, being rich in rhamnose,
      galactose, and uronic acids, can be categorized on the basis of its sugar
      composition as a rhamnogalacturonan type of gum. The rheological measurements
      performed on the gum suggest that above 0.6% (w/v) it shows a Newtonian behavior
      and shear rate thinning behavior as a function of gum concentration. The
      viscoelastic behavior of gum kondagogu solutions (1 and 2%) in aqueous as well as
      in 100 mM NaCl solution exhibits a typical gel-like system. The G' (viscous
      modulus)/ G'' (elastic modulus) ratios of native gum kondagogu (1 and 2%) in
      aqueous solution were found to be 1.89 and 1.85 and those in 100 mM NaCl to be
      1.54 and 2.2, respectively, suggesting a weak gel-like property of the polymer.
      Crossover values of G' and G'' were observed to be at frequencies of 0.432 Hz for
      1% and 1.2 Hz for 2% for native gum in aqueous condition, indicating a
      predominantly liquid- to solid-like behavior, whereas crossover values of 2.1 Hz
      for 1% and 1.68 Hz for 2% gum in 100 mM NaCl solution suggest a larger elastic
      contribution.

PMID- 18318495
TI  - Formation of pyrazines and a novel pyrrole in Maillard model systems of 1,3
      dihydroxyacetone and 2-oxopropanal.
AB  - Alkylpyrazines are a very important class of Maillard flavor compounds, but their
      mechanism of formation is complex and consists of different pathways. The model
      reaction of 20 different amino acids with 1,3-dihydroxyacetone, as a precursor of
      2-oxopropanal, was studied by means of SPME-GC-MS to investigate the involvement
      of the amino acid side chain in the substitution pattern of the resulting
      pyrazines. 2,5-Dimethylpyrazine was quantitatively the most important pyrazine
      formed from all of the amino acids. The amino acid side chain is not involved in
      its formation. The substituents of other less abundant pyrazines resulted mainly
      from the incorporation of the Strecker aldehyde or aldol condensation products in
      the intermediate dihydropyrazine. The importance of different reaction mechanisms
      was evaluated, taking into account the pattern of pyrazines identified. In the
      solvent extracts of aqueous model reactions of 2-oxopropanal with amino acids,
      the main reaction product was not a pyrazine but a novel pyrrole. This pyrrole
      was identified as 2,5-diacetyl-3-methyl-1 H-pyrrole by means of spectral
      analysis, secured by chemical synthesis. A reaction mechanism for its formation
      was proposed and evaluated. The influence of various reaction conditions on the
      formation of 2,5-diacetyl-3-methyl-1 H-pyrrole and 2,5-dimethylpyrazine in the
      model reaction of alanine with 2-oxopropanal was studied. These results
      underscore the importance of the ratio of the different reagents and the presence
      of water in the resulting flavor formation in the Maillard reaction.

PMID- 18318496
TI  - Investigation on the lipid- and cholesterol-lowering abilities of biocellulose.
AB  - The present study investigated and compared the physicochemical properties as
      well as the hypolipidemic and hypocholesterolemic effects between plant cellulose
      and biocellulose. Biocellulose had higher water-holding and cation-exchange
      capacities than plant cellulose ( approximately 2- and 6-fold, respectively). The
      results showed that the administration of plant cellulose and biocellulose to
      hamsters effectively ( P < 0.05) decreased the concentrations of serum
      triglyceride (by 13.9-55.5%), serum total cholesterol (by 17.4-27.9%), serum low
      density lipoprotein cholesterol (by 41.9-47.9%), liver total lipids (by 6.4
      10.3%), and liver cholesterol (by 11.8-16.3%). Feeding plant cellulose and
      biocellulose also enhanced the excretion of total lipids (144-182%), cholesterol
      (136-203%), and bile acids (259-479%) in feces. The efficacy of biocellulose in
      lowering serum lipids and cholesterol in hamsters was significantly higher than
      that of plant cellulose. These results suggested that biocellulose could be a
      promising low-calorie bulking ingredient for the development of novel fiber-rich
      functional foods of different forms such as powder, gelatinous, or shred forms.

PMID- 18318497
TI  - Enantioselective degradation and ecotoxicity of the chiral herbicide diclofop in
      three freshwater alga cultures.
AB  - Aryloxyphenoxypropanoates are a class of chiral herbicides. They have a pair of
      enantiomers, only the R(+) form of which is herbicidally active. Diclofop, the
      model compound of these herbicides, is commercialized as the racemate of the
      ester form, diclofop-methyl, consisting of a 1:1 mixture of the enantiomers. This
      study evaluated the enantioselectivity in aquatic toxicity and biodegradation of
      diclofop and diclofop-methyl. The herbicidally inactive S(-) enantiomers of both
      diclofop-methyl and diclofop were similar to or higher than the corresponding
      R(+) forms in toxicity to algae, depending on specific species. Although no
      enantiomeric conversion occurred for diclofop-methyl and diclofop, the difference
      in the enantioselective degradation of these herbicides observed in algae
      cultures suggested that their application forms were an important factor
      determining their enantioselective environmental behavior. The cell permeability
      and heat treatment of algae revealed that the enantioselective degradation of
      diclofop in algae cultures was governed primarily by the facilitated uptake by
      algae, whereas the enantioselective toxicity was primarily governed by the
      passive uptake. These results suggested that the acute toxicity test such as the
      96 h EC 50 was insufficient to assess the ecological risk of chiral pesticides
      because of the differential degradation as well as possibly differential action
      sites of enantiomers. From this study, it was concluded that the enantioselective
      degradation and toxicity of chiral herbicides may result in their
      ecotoxicological effects being difficult to predict and that specific attention
      should thus be paid to currently used racemic pesticides as less active or
      inactive enantiomers may pose higher ecological risks.

PMID- 18318498
TI  - Formation of peptide-bound Heyns compounds.
AB  - The reaction of the Nalpha-hippuryllysine (BzGK) with fructose was investigated
      in two model systems to obtain an insight in fructose-induced modification of
      lysine in bakery products. After BzGK and fructose had been heated in a buffered
      low-moisture model system (80 degrees C, 60 min, aW = 0.86, pH 7.4), formation of
      epimeric Heyns compounds Nalpha-hippuryl-Nepsilon-glucosyl-lysine (BzGGlcK) and
      Nalpha-hippuryl-Nepsilon-mannosyl-lysine (BzGManK) was clearly demonstrated using
      RP-HPLC with UV as well as MS detection. The Amadori compound Nalpha-hippuryl
      Nepsilon-fructosyl-lysine (BzGFruK) was formed in glucose-containing samples.
      When BzGK was added to the dough of fructose-containing biscuits, the Heyns
      compounds were detectable after baking at 175 degrees C for 7 min. The yields of
      the Heyns compounds in the fructose-containing biscuits and the yield of the
      Amadori compound in the glucose-containing biscuits were determined to 33 and
      63%, pointing to the fact that formation of substantial amounts of Heyns products
      is very likely in fructose-containing bakery products.

PMID- 18318499
TI  - The flavonoids of tomatoes.
AB  - Tomatoes ( Lycopersicon esculentum Mill.) have been recognized as an important
      source of dietary flavonoids because of a high consumption worldwide. The
      qualitative and quantitative flavonoid compositions of assorted tomato cultivars
      including individual quantitative contributions of the five most significant
      flavonoids have been determined in this work. The dihydrochalcone phloretin 3',5'
      di-C-beta-glucopyranoside and the flavonol quercetin 3-O-(2''-O-beta
      apiofuranosyl-6''-O-alpha-rhamnopyranosyl-beta-glucopyranoside) were identified
      for the first time in Solanaceae spp. and found to be among the main flavonoids
      in all cultivars. Phloretin 3',5'-di-C-glc is the first C-glycoside identified in
      tomatoes and also the first dihydrochalcone from this species. In addition,
      chalconaringenin, kaempferol 3-rutinoside, and quercetin 3-rutinoside (rutin),
      though previously reported to occur in tomato, were fully characterized by
      extensive use of 2D NMR techniques and high-resolution LCMS. The total flavonoid
      content of different tomato types varied from 4 to 26 mg 100 (-1) g FW with
      chalconaringenin as the predominant compound comprising 35 to 71% of the total
      flavonoid content. The individual quantities of quercetin 3-O-(2''- O-beta
      apiofuranosyl-6''- O-alpha-rhamnopyranosyl-beta-glucopyranoside) and phloretin
      3',5'-di-C-beta-glucopyranoside was similar to that of rutin in several
      cultivars.

PMID- 18318500
TI  - Enzymatic removal of off-flavors from apple juice.
AB  - Contaminating microorganisms such as Actinomycetes, Alicyclobacillus, and
      Chlostridium can generate off-flavors in apple juices. Such bacterial metabolites
      represent, besides phenol types such as guaiacol and 2,6-dibromophenol, a broad
      range of other chemicals, for example, geosmin, 2-methylisoborneol, or alpha
      terpineol. A laccase from Trametes hirsuta was purified, immobilized, and applied
      for the selective elimination of off-flavor substances in apple juice caused by
      microbial contamination. The evaluation using GC-MS showed that enzymatic
      treatment could reduce the amount of guaiacol and 2,6-dibromophenol in apple
      juice significantly by 99 and 52%, respectively. Upon addition of mediators, the
      degradation could be increased and the spectrum of substrates extented.
      Furthermore, commercial apple juices spiked with off-flavors were treated in a
      continuous-flow reactor and tested by sensory evaluation.

PMID- 18318501
TI  - Generating elastic, biodegradable polyurethane/poly(lactide-co-glycolide) fibrous
      sheets with controlled antibiotic release via two-stream electrospinning.
AB  - Damage control laparotomy is commonly applied to prevent compartment syndrome
      following trauma but is associated with new risks to the tissue, including
      infection. To address the need for biomaterials to improve abdominal laparotomy
      management, we fabricated an elastic, fibrous composite sheet with two distinct
      submicrometer fiber populations: biodegradable poly(ester urethane) urea (PEUU)
      and poly(lactide-co-glycolide) (PLGA), where the PLGA was loaded with the
      antibiotic tetracycline hydrochloride (PLGA-tet). A two-stream electrospinning
      setup was developed to create a uniform blend of PEUU and PLGA-tet fibers.
      Composite sheets were flexible with breaking strains exceeding 200%, tensile
      strengths of 5-7 MPa, and high suture retention capacity. The blending of PEUU
      fibers markedly reduced the shrinkage ratio observed for PLGA-tet sheets in
      buffer from 50% to 15%, while imparting elastomeric properties to the composites.
      Antibacterial activity was maintained for composite sheets following incubation
      in buffer for 7 days at 37 degrees C. In vivo studies demonstrated prevention of
      abscess formation in a contaminated rat abdominal wall model with the implanted
      material. These results demonstrate the benefits derivable from a two-stream
      electrospinning approach wherein mechanical and controlled-release properties are
      contributed by independent fiber populations and the applicability of this
      composite material to abdominal wall closure.

PMID- 18318503
TI  - Photoinduced removal of the franck-condon blockade in single-electron inelastic
      charge transmission.
AB  - A new mechanism of charge transmission through a metal-molecule-metal junction is
      suggested that is based on optical driving of electronic transitions in the
      neutral and singly charged molecular state. The effects of strong electron
      vibrational coupling, intramolecular vibrational energy redistribution, and
      molecular de-excitation caused by electron-hole pair formation in the leads are
      taken into account. It is shown that current suppression due to the Franck-Condon
      blockade can be overcome by opening new transmission channels via
      photoexcitation.

PMID- 18318502
TI  - Using 3'-bridging phosphorothiolates to isolate the forward DNA cleavage reaction
      of human topoisomerase IIalpha.
AB  - The ability to cleave DNA is critical to the cellular and pharmacological
      functions of human type II topoisomerases. However, the low level of cleavage at
      equilibrium and the tight coupling of the cleavage and ligation reactions make it
      difficult to characterize the mechanism by which these enzymes cut DNA.
      Therefore, to establish a system that isolates topoisomerase II-mediated DNA
      scission from ligation, oligonucleotide substrates were developed that contained
      a 3'-bridging phosphorothiolate at the scissile bond. Scission of these
      substrates generates a 3'-terminal -SH moiety that is a poor nucleophile relative
      to the normal 3'-terminal -OH group. Consequently, topoisomerase II cannot
      efficiently ligate phosphorothiolate substrates once they are cleaved. The
      characteristics of topoisomerase IIalpha-mediated cleavage of phosphorothiolate
      oligonucleotides were identical to those seen with wild-type substrates, except
      that no ligation was observed. This unidirectional accumulation of cleavage
      complexes provided critical information regarding coordination of the protomer
      subunits of topoisomerase IIalpha and the mechanism of action of topoisomerase II
      poisons. Results indicate that the two enzyme subunits are partially coordinated
      and that cleavage at one scissile bond increases the degree of cleavage at the
      other. Furthermore, anticancer drugs such as etoposide and amsacrine that
      strongly inhibit topoisomerase II-mediated DNA ligation have little effect on the
      forward scission reaction. In contrast, abasic sites that increase levels of
      cleavage complexes without affecting ligation stimulate the forward rate of
      scission. Phosphorothiolate substrates provide significant advantages over
      traditional "suicide substrates" and should be valuable for future studies on DNA
      scission and the topoisomerase II-DNA cleavage complex.

PMID- 18318504
TI  - Self-contained, biomolecular motor-driven protein sorting and concentrating in an
      ultrasensitive microfluidic chip.
AB  - We developed a molecular sorter that operates without external power or control
      by integrating the microtubule-based, biological motor kinesin into a
      microfluidic channel network to sort, transport, and concentrate molecules. In
      our devices, functionalized microtubules that capture analyte molecules are
      steered along kinesin-coated microchannel tracks toward a collector structure,
      concentrated, and trapped. Using fluorescent analyte molecules and nanoliter
      sample volumes, we demonstrated 14 fM sensitivity, even in the presence of high
      concentrations of other proteins.

PMID- 18318505
TI  - MspA Porin-Gold Nanoparticle Assemblies: Enhanced Binding through a Controlled
      Cysteine Mutation.
AB  - In this study, the interactions of two gold nanoparticles of different sizes
      (average diameters of 3.7 +/- 2.6 and 17 +/- 3 nm) with octameric mycobacterial
      porin A from Mycobacterium smegmatis (MspA) and a mutant of MspA featuring a
      cysteine mutation in position 126 (Q126C) are investigated. From the observation
      of enhanced photoluminescence quenching, it is inferred that the presence of
      eight cysteines in the MspA Q126C mutant significantly enhances the binding of
      selected small gold nanoparticles within the inner pore of MspA. The large gold
      nanoparticle/porin complex shows photoluminescence enhancement, which is expected
      since the larger nanoparticles cannot dock within the homopore of MspA due to
      size exclusion. In addition to the fluorescence experiments, observation of
      energy transfer from the small gold nanoparticles to the MspA shows the close
      proximity of the small gold nanoparticles with the porin. Interestingly, the
      energy transfer of the large nanoparticle/MspA complex is completely missing.
      From high-performance liquid chromatography data, the estimated binding constants
      for small Au@MspA, large Au@MspA, small Au@MspAcys, and large Au@MspAcys are 1.3
      x 10 (9), 2.22 x 10 (10), > 10 (12) (irreversible), and 1.7 x 10 (10),
      respectively.

PMID- 18318506
TI  - The function of a TiO2 compact layer in dye-sensitized solar cells incorporating
      "planar" organic dyes.
AB  - We present a device based study into the operation of liquid electrolyte dye
      sensitized solar cells (DSSC's) using organic dyes. We find that, for these
      systems, it is entirely necessary to employ a compact TiO2 layer between the
      transparent fluorine doped SnO2 (FTO) anode and the electrolyte in order to
      reduce charge recombination losses. By incorporation of a compact layer, the
      device efficiency can be increased by over 160% under simulated full sun
      illumination and more than doubled at lower light intensities. This is strong
      evidence that the more widely employed ruthenium based sensitizers act as to
      "insulate" the anode against recombination losses and that many planar organic
      dyes employed in DSSC's could greatly benefit from the use of a compact TiO2
      blocking layer. This is in strong contrast to DSSC's sensitized with ruthenium
      based systems, where the introduction of compact TiO2 has only marginal effects
      on conversion efficiencies.

PMID- 18318507
TI  - Protonation effects on the branching ratio in photoexcited single-walled carbon
      nanotube dispersions.
AB  - The ensemble PL quantum yield for raw single-walled carbon nanotubes (SWNTs)
      dispersed in sodium cholate (SC) is approximately 5 times greater than that for
      the same raw SWNTs dispersed in sodium dodecyl sulfate (SDS) and approximately 10
      times greater than the quantum yield of purified SWNTs dispersed in SC.
      Absorbance and Raman spectra indicate that purified SC-dispersed SWNTs and raw
      SDS-dispersed SWNTs are hole-doped by protonation. Experiments comparing PL
      emission efficiency using E2 and E1 excitation show that protonation
      significantly affects the E2 --> E1 relaxation process, which has typically been
      assumed to occur with unit efficiency. The E2 --> E 1 relaxation is 5 times more
      efficient in producing E 1 PL when SWNTs are unprotonated and protected by the SC
      surfactant. The results provide clear evidence that extrinsic factors, such as
      residual acids and the specific nature of SWNT-surfactant and SWNT-solvent
      interactions, can significantly affect measured SWNT luminescence quantum yields.

PMID- 18318508
TI  - Method of measuring oligonucleotide-metal affinities: interactions of the
      thrombin binding aptamer with K+ and Sr2+.
AB  - We report a new, mass spectrometry-based method for measuring affinity constants
      for specific metal ion binding to DNA, particularly for quadruplex DNA. This
      method, which is applicable to other systems, utilizes the gas-phase signal
      fractions, as determined by mass spectrometry, from the bound and unbound species
      as input into a mathematical model that determines various parameters, one of
      which is the binding affinity constant. The system used to develop and test the
      model was the thrombin-binding aptamer, an appropriate quadruplex structure that
      binds both K+ and Sr2+ cations. Using this method, we measured the binding
      constants of potassium and strontium cations with the quadruplex structure to be
      5000 and 240 nM, respectively. We then applied the method to measure the change
      in enthalpy of the binding of strontium cations to the thrombin binding aptamer.
      The DeltaH for this interaction is -71 kJ/mol (-17 kcal/mol). The binding
      constant measurements are consistent with earlier measurements on the same
      system, and the measured change in enthalpy is in excellent agreement with
      previous work.

PMID- 18318509
TI  - Study of cell antigens and intracellular DNA by identification of element
      containing labels and metallointercalators using inductively coupled plasma mass
      spectrometry.
AB  - The enumeration of absolute cell numbers and cell proliferation in clinical
      samples is important for diagnostic and research purposes. Detection of cellular
      DNA with fluorescent dyes is the most commonly used approach for cell enumeration
      in cytometry. Inductively coupled plasma mass spectrometry (ICPMS) has been
      recently introduced to the field of protein and cell surface antigen
      identification via ICPMS-linked immunoassays using element-labeled affinity
      reagents such as gold and lanthanide-conjugated antibodies. In the present work,
      we describe novel methods for using metallointercalators that irreversibly bind
      DNA and low concentrations of rare earth metals added to cell growth media for
      rapid and sensitive measurement of cell numbers by mass spectrometry. We show
      that Ir- and Rh-containing metallointercalators are useful reagents for labeling
      cells and normalizing signals when studying antigen expression on different types
      and numbers of cells. Results are presented for solution analysis performed by
      conventional ICPMS and compared to measurements obtained on the novel flow
      cytometer mass spectrometer (FC-MS) instrument, designed to analyze multiple
      antigens and DNA simultaneously in single cells.

PMID- 18318510
TI  - Alternating current electrokinetic motion of colloidal particles on
      interdigitated microelectrodes.
AB  - Alternating current (ac) electrokinetic motion of colloidal particles suspended
      in an aqueous medium and subjected to a spatially nonuniform ac electric field
      are examined using a simple theoretical model that considers the relative
      magnitudes of dielectrophoresis, electrophoresis, ac-electroosmosis, and Brownian
      motion. Dominant electrokinetic forces are explained as a function of the
      electric field frequency, amplitude, and conductivity of the suspending medium
      for given material properties and geometry. Parametric experimental validations
      of the model are conducted utilizing interdigitated microelectrodes with
      polystyrene and gold particles and Clostridium sporogenes bacterial spores. The
      theoretical model provides quantitative descriptions of ac electrokinetic
      transport for the given target species in a wide spectrum of electric field
      amplitude and frequency and medium conductivity. The presented model can be used
      as an effective framework for design and optimization of ac electrokinetic
      devices.

PMID- 18318511
TI  - Fluorescein isothiocyanate linked immunoabsorbent assay based on surface-enhanced
      resonance Raman scattering.
AB  - By using fluorescein isothiocyanate (FITC) as a Raman probe, we have developed a
      simple and sensitive method for an immunoassay based on surface-enhanced
      resonance Raman scattering (SERRS). For the first time, a SERRS-based immunoassay
      on the bottom of a microtiter plate is reported. We have applied the main
      pretreatment method of enzyme-linked immunoabsorbent assay (ELISA) to the present
      study. In this method, SERRS spectra of FITC are measured after several
      continuous steps of antigen coating, blocking, antibody adding, and colloidal
      silver staining. Human immunoglobulin G (IgG) and FITC-antihuman IgG are used for
      the immunoreaction. The proposed method has several advantages for immunoassay.
      First, we can determine the concentration of antigens via the intensity of a
      SERRS signal of FITC molecules that are attached to antibodies without an enzyme
      reaction, and thus the process is simple and reagent saving. Second, one can
      obtain SERRS spectra of FITC directly from silver aggregates on the bottom of a
      microtiter plate without displacement. Third, by using SERRS of FITC, the present
      method is sensitive enough to detect antigens at the concentration of 0.2 ng/mL,
      which is comparable to ELISA. Results are presented to demonstrate that the
      proposed SERRS-based immunoassay may have great potential as a high-sensitivity
      and high-throughout immunoassay.

PMID- 18318512
TI  - Effect of substituting oxygen for terminal nitrogen in aniline oligomers: a DFT
      comparison of hydroxyl and amino terminated aniline trimers.
AB  - Quantum mechanical density functional theory (DFT) calculations are reported for
      N,N'-bis(4'-hydroxyphenyl)-1,4-quinonediimine [henceforth referred to as the
      hydroxyl terminated trimer], a derivative of previously investigated aniline
      trimers. Calculations are also reported on all isomers, common oxidations states,
      and hydrochloride salts of this material. The significance of replacing terminal
      amino groups by hydroxyl groups is detailed. The hydroxyl terminated trimer has a
      calculated electron affinity larger than that of the corresponding amino
      terminated aniline trimer N,N'-bis(4'-aminophenyl)-1,4-quinonediimine. The
      electron affinity of the anti conformer of the hydroxyl terminated emeraldine
      base trimer is 0.059767 hartrees (37.5 kcal mol(-1)), whereas that of the amino
      terminated form is 0.052728 (33.1 kcal mol(-1)). The electron affinity of the
      anti conformer of the hydroxyl terminated emeraldine dihydrochloride salt trimer
      is 0.130546 hartrees (81.9 kcal mol(-1)), whereas that of the amino terminated
      dihydrochloride salt is only 0.118972 (74.7 kcal mol(-1)). Because previous work
      has suggested that a larger electron affinity in the salt form leads to improved
      effectiveness in the role of corrosion inhibitor, these high-level calculations
      suggest a new and superior material for this application.

PMID- 18318513
TI  - Instability of the Al4(2-) "all-metal aromatic" ion and its implications.
AB  - Al42 - is a prototype structural unit of a new class of "all-metal aromatic"
      molecules. Without stabilizing counterions this species is unstable with respect
      to electron autodetachment in the gas phase. We estimated the height of the
      repulsive Coulomb barrier to approximately 2.7 eV and calculated a lifetime of 9
      fs. This is a short lifetime: The only way to study the isolated dianion
      experimentally is to use electron scattering techniques. Investigations of the
      validity of bound-state quantum chemical calculations on the isolated species
      show that the results suffer from significant admixture of continuum states to
      the bound-state wave function depending on the basis set. Calculations of
      molecular properties can therefore give essentially arbitrary results for this
      ill-defined system, as is demonstrated for the energy and nuclear magnetic
      shieldings. This substantiates that results from calculations on the isolated
      dianion should be approached with caution.

PMID- 18318514
TI  - Theoretical study of the reaction mechanism of HCN+ and CH4 of relevance to
      Titan's ion chemistry.
AB  - Titan is the largest satellite of Saturn. In its atmosphere, CH4 is the most
      abundant neutral after nitrogen. In this paper, the complex doublet potential
      energy surface related to the reaction between HCN+ and CH4 is investigated at
      the B3LYP/6-311G(d,p), CCSD(T)/6-311G++(3df,2pd)(single-point), and QCISD/6
      311G(d,p) computational levels. A total of seven products are located on the PES.
      The initial association of HCN+ with CH4 is found to be a prereaction complex 1
      (HCNHCH3(+)) without barrier. Starting from 1, the most feasible pathway is the
      direct H-abstraction process (the internal C-H bond dissociation) leading to the
      product P1 (HCNH++CH3). By C-C addition, prereaction complex 1 can form
      intermediate 2 (HNCHCH3(+)) and then lead to the product P2 (CH3CNH++H). The rate
      controlling step of this process is only 25.6 kcal/mol. It makes the Path P2 (1)
      R --> 1 --> TS1/2 --> 2 --> TS2/P2 --> P2 another possible way for the reaction.
      P3 (HCNCH3(+) + H), P5 (cNCHCH2(+) + H2), and P6 (NCCH3(+) + H2) are exothermic
      products, but they have higher barriers (more than 40.0 kcal/mol); P4 (H + HCN +
      CH3(+)) and P7 (H + H2 + HCCNH+) are endothermic products. They should be
      discovered under different experimental or interstellar conditions. The present
      study may be helpful for investigating the analogous ion-molecule reaction in
      Titan's atmosphere.

PMID- 18318515
TI  - Non-RRKM dynamics in the CH3O2 + NO reaction system.
AB  - Quasi-classical trajectory (QCT) calculations on a model potential energy surface
      (PES) show strong deviations from statistical Rice-Ramsperger-Kassel-Marcus
      (RRKM) rate theory for the decomposition reaction (1) CH3OONO* --> CH3O + NO2,
      where the highly excited CH3OONO* was formed by (2) CH3O2 + NO --> CH3OONO*. The
      model PES accurately describes the vibrational frequencies, structures, and
      thermochemistry of the cis- and trans-CH3OONO isomers; it includes cis-trans
      isomerization in addition to reactions 1 and 2 but does not include nitrate
      formation, which is too slow to affect the decay rate of CH3OONO*. The QCT
      results give a strongly time-dependent rate constant for decomposition and damped
      oscillations in the decomposition rate, not predicted by statistical rate theory.
      Anharmonicity is shown to play an important role in reducing the rate constant by
      a factor of 10 smaller than predicted using classical harmonic RRKM theory
      (microcanonical variational transition state theory). Master equation simulations
      of organic nitrate yields published previously by two groups assumed that RRKM
      theory is accurate for reactions 1 and 2 but required surprising parametrizations
      to fit experimental nitrate yield data. In the present work, it is hypothesized
      that the non-RRKM rate of reaction (1) and vibrational anharmonicity are at least
      partly responsible for the surprising parameters.

PMID- 18318516
TI  - Geometries, stabilities, and vibrational properties of bimetallic Mo2-doped Gen
      (n = 9-15) clusters: a density functional investigation.
AB  - Geometries of the bimetallic Mo2Gen (n = 9-15) clusters have been investigated
      systematically with the density functional approach. The relative stabilities and
      charge-transfer and vibrational properties of these clusters are presented and
      discussed. The dominant geometries of Mo2Gen (n = 9-12) clusters can be described
      as one Mo atom inside a Ge cage and another Mo atom on the surface at smaller
      sizes with n = 9-12. Interestingly, the stable geometry of Mo2Ge9 cluster has the
      framework which is analogous to a recent experimental observation (Goicoechea, J.
      M.; Sevov, S. C. J. Am Chem. Soc. 2006, 128, 4155). The calculated fragmentation
      energies and the obtained relative stabilities demonstrate that the remarkable
      Mo2-doped Ge12 is the most stable species of all different sized clusters. The
      critical size of Mo2-encapsulated cagelike germanium clusters appears at n = 15.
      The largest energy gap and strongest stability of Mo2Ge12 enable this species to
      be a unit of multiple metal Mo-doped germanium nanotubes. Vibrational mode
      analyses of Mo2Gen clusters demonstrate that the Mo-Mo stretching vibrations are
      sensitive to the geometries of the germanium frame, and that the point-group
      symmetry of germanium clusters can vary the Mo-Mo stretching vibration relative
      to the IR inactive vibration.

PMID- 18318517
TI  - Semiempirical double-hybrid density functional with improved description of long
      range correlation.
AB  - The recently proposed new family of "double-hybrid" density functionals [Grimme,
      S. J. Chem. Phys. 2006, 124, 34108] replaces a fraction of the semi-local
      correlation energy by a non-local correlation energy expression that employs the
      Kohn-Sham orbitals in second-order many-body perturbation theory. These
      functionals have provided results of high accuracy over a wide range of
      properties but fail to accurately describe long-range van der Waals interactions.
      In this work, a distance-dependent scaling factor for the non-local correlation
      energy is introduced to address this problem, and two new double-hybrid density
      functionals are proposed. The new functionals are optimized with the finite cc
      pVTZ basis on training sets of atomization energies and intermolecular
      interaction energies. They are compared against (scaled) second-order Moller
      Plesset perturbation theories and popular density functionals including the
      hybrid-GGA functional B3-LYP and the first double-hybrid functional (B2-PLYP).
      Tests are performed on an extensive set including reaction energies, barrier
      heights, weakly interacting complexes, transition-metal systems, molecular
      geometries, and harmonic vibrational frequencies. Within the cc-pVTZ atomic
      orbital basis, we have demonstrated the ability to find a parametrization scheme
      which is simultaneously able to describe thermochemistry and weakly bound systems
      with a satisfactory degree of accuracy.

PMID- 18318518
TI  - Isotope effects in isotope-exchange reactions: evidence for a large 12C/13C
      kinetic isotope effect in the gas phase.
AB  - The O-exchange reaction between CO2+ and CO is triggered by two different
      entrance channels in 13C-labeled systems. The unimolecular dissociation of the
      C13CO3(+) reactive intermediate is investigated at varying energies by mass
      spectrometric techniques. An almost "one-way" O-exchange at energies close to the
      dissociation threshold discloses a remarkably large intramolecular 12C/13C
      kinetic isotope effect ranging from 6.0 to 7.3 +/- 0.5.

PMID- 18318519
TI  - Structure, stability, and dynamics of canonical and noncanonical base pairs:
      quantum chemical studies.
AB  - The importance of non-Watson-Crick base pairs in the three-dimensional structure
      of RNA is now well established. The structure and stability of these noncanonical
      base pairs are, however, poorly understood. We have attempted to understand
      structural features of 33 frequently occurring base pairs using density
      functional theory. These are of three types, namely (i) those stabilized by two
      or more polar hydrogen bonds between the bases, (ii) those having one polar and
      another C-H...O/N type interactions, and (iii) those having one H-bond between
      the bases and another involving one of the sugars linked to the bases. We found
      that the base pairs having two polar H-bonds are very stable as compared to those
      having one C-H...O/N interaction. Our quantitatively analysis of structures of
      these optimized base pairs indicates that they possess a different amount of
      nonplanarity with large propeller or buckle values as also observed in the
      crystal structures. We further found that geometry optimization does not modify
      the hydrogen-bonding pattern, as values of shear and open angle of the base pairs
      remain conserved. The structures of initial crystal geometry and final optimized
      geometry of some base pairs having only one polar H-bond and a C-H...O/N
      interaction, however, are significantly different, indicating the weak nature of
      the nonpolar interaction. The base pair flexibility, as measured from normal-mode
      analysis, in terms of the intrinsic standard deviations of the base pair
      structural parameters are in conformity with those calculated from RNA crystal
      structures. We also noticed that deformation of a base pair along the stretch
      direction is impossible for all of the base pairs, and movements of the base
      pairs along shear and open are also quite restricted. The base pair opening mode
      through alteration of propeller or buckle is considerably less restricted for
      most of the base pairs.

PMID- 18318520
TI  - Two-dimensional gradient mapping technique useful for detailed spectral analysis
      of polymer transition temperatures.
AB  - This paper demonstrates the potential of a two-dimensional (2D) gradient mapping
      technique that utilized the eigenvalue manipulating transformation (EMT) of the
      spectral data set. The EMT technique, by lowering the power of a set of
      eigenvalues associated with the original data, enhances the contributions of
      minor principle components (PCs). The operation converts the original spectral
      data set to the one with subtle differences among the responses of the system
      being exaggerated. Small shoulders and obscure minor features may become much
      more visible, because such small differentiating features are often captured only
      by the minor PCs enlarged by the EMT treatment. This improvement for 2D mapping
      is potentially very important to determine the transition temperatures, which are
      not readily detected in convention spectral analysis.

PMID- 18318521
TI  - Incorporating perylene moiety into poly(phenothiazine-co-bithiophene) backbone
      for higher charge transport.
AB  - Low band gap pi-conjugated polymers composed of phenothiazine, bithiophene, and
      perylene moieties were prepared in high yields by using a palladium-catalyzed
      Suzuki coupling reaction. The polymers were characterized by NMR, gel permeation
      chromatography, and elemental analysis. The characterizations revealed that high
      molecular weight (weight-average molecular weight up to 42,400 g/mol) polymers
      were thermally stable with a decomposition temperature in the region of 338-354
      degrees C and their glass transition temperatures (Tg) ranging from 124 to 136
      degrees C. All polymers demonstrated broad optical absorption in the region of
      300-550 nm with efficient blue-green light emission. The absorption was broadened
      further (for ca. 50 nm) when the perylene moiety was incorporated. Cyclic
      voltammograms displayed that the p- and n-doping processes of all the polymers
      were partially reversible and that electrochemical band gaps were as low as -2.30
      eV with the incorporation of a perylene moiety. The hole mobility of polymers was
      evaluated by using the space-charge-limited current model with a device structure
      of ITO/PEDOT:PSS/polymer/Ca. The results show that the incorporation of perylene
      is beneficial for improving the hole mobility of the conjugated polymers.

PMID- 18318522
TI  - Solid phases of cyclopentane: combined experimental and simulation study.
AB  - The phase diagram of cyclopentane has been studied by powder neutron diffraction,
      providing diffraction patterns for phases I, II, and III, over a range of
      temperatures and pressures. The putative phase IV was not observed. The structure
      of the ordered phase III has been solved by single-crystal diffraction.
      Computational modeling reveals that there are many equienergetic ordered
      structures for cyclopentane within a small energy range. Molecular dynamics
      simulations reproduce the structures and diffraction patterns for phases I and
      III and also show an intermediate disordered phase, which is used to interpret
      phase II.

PMID- 18318523
TI  - Three different tyrosyl radicals identified in L-tyrosine HCl crystals upon gamma
      irradiation: magnetic characterization and temporal evolution.
AB  - High-frequency electron paramagnetic resonance (EPR) and X-band electron-nuclear
      double resonance (ENDOR) spectroscopies were used to investigate the effect of
      gamma-irradiation on single crystals of L-tyrosine hydrochloride at room
      temperature. The oxidation product is the tyrosyl radical formed by hydrogen
      abstraction from the phenolic group; interestingly, on freshly irradiated
      crystals, two tyrosyl radicals were identified, characterized by slightly
      different magnetic parameters. In particular, one of the two radicals, with a gxx
      value of 2.00621, has its phenoxyl oxygen strongly hydrogen-bonded to one or more
      donors; to our knowledge, this is the lower gxx value reported for tyrosyl
      radicals. These two oxidation radicals are found to evolve very slowly to a
      third, single more stable radical conformation. To interpret the experimental
      data, a possible molecular scenario is presented, where the process of radical
      formation can be seen as a hydrogen atom transfer or a proton-coupled electron
      transfer. These processes seem to be controlled by the specific network of
      hydrogen-bond interactions present in the crystal. The results are discussed in
      relation to their relevance for the interpretation of EPR spectra of tyrosyl
      radicals in biological systems.

PMID- 18318524
TI  - Effect of macromolecular polydispersity on diffusion coefficients measured by
      Rayleigh interferometry.
AB  - Rayleigh interferometry has been extensively used for the precise determination
      of diffusion coefficients for binary and ternary liquid mixtures. For ternary
      mixtures, the 2x2 matrix of multicomponent diffusion coefficients is obtained.
      Polydispersity adds complexity to the meaning of these measured diffusion
      coefficients. Here we discuss three important issues of polydispersity regarding
      the diffusion measurements extracted from this interferometric technique. First,
      we report novel equations for the extraction of diffusion moments from the
      Rayleigh interferometric pattern. These moments are used to define polydispersity
      parameters for macromolecular systems. We have experimentally determined mean
      diffusion coefficients and polydispersity parameters for aqueous solutions of
      poly(ethylene glycol) and poly(vinyl alcohol) at 25 degrees C. Aqueous solutions
      of poly(ethylene glycol) mixtures were used to examine the accuracy of the
      polydispersity parameters. Second, we compare Rayleigh interferometry to dynamic
      light scattering. Specifically, we have performed diffusion measurements on the
      same system using both techniques. To our knowledge, no direct experimental
      comparison between dynamic light scattering and classical methods for the
      measurements of diffusion coefficients has been previously reported in relation
      to polydispersity. We find that substantial discrepancies (i.e., 1 order of
      magnitude) between the mean diffusion coefficients obtained from these two
      different techniques can be observed when polydispersity is large. Third, for two
      solute mixtures with one polydisperse solute, we report a novel corrective
      procedure for extracting accurate ternary diffusion coefficients from Rayleigh
      interferometry. Computer simulations were used to examine the accuracy of the
      extracted ternary diffusion coefficients.

PMID- 18318525
TI  - The protein "glass" transition and the role of the solvent.
AB  - Hydrated proteins undergo a change in their dynamical properties in the
      neighborhood of a temperature. The change of dynamics has been likened to glass
      transition of glass-forming substances because similar properties were found.
      However, a complete understanding of the conformation fluctuations of hydrated
      proteins and their relation to the dynamics of the solvent is still not
      available, possibly due to the protein molecules being more complex than ordinary
      glass-formers. For this reason, we turn our attention to the experimental
      findings of the dynamics of mixtures of water with simpler glass-formers (small
      molecules and polymers). Two major relaxation processes have been observed in
      these aqueous mixtures. One is the structural alpha-relaxation of the hydrophilic
      glass-former hydrogen bonded to the water, which is responsible for glass
      transition. The other one is the local secondary beta-relaxation of water in the
      mixture. Remarkably, these two relaxation processes in aqueous mixtures have
      analogues in hydrated proteins with the same properties. The conformation
      fluctuations of the protein and the relaxation of the solvent in hydrated
      proteins behave like the alpha-relaxation of the hydrophilic glass-former
      hydrogen bonded to the water and the beta-relaxation of water in other aqueous
      mixtures, respectively. At low temperatures, the Arrhenius activation energy of
      the relaxation time of the solvent in a hydrated protein is almost the same as
      that of the beta-relaxation of water in the glassy states of aqueous mixtures.
      The Arrhenius T-dependence of the solvent relaxation times no longer holds at
      temperatures that exceed the "glass" transition temperature of the hydrated
      protein, defined as the temperature at which the conformation relaxation time is
      very long. This behavior of the solvent in hydrated proteins is similar to that
      found in the beta-relaxation of water in aqueous mixtures when crossing the glass
      transition temperature of the mixture (Capaccioli, S.; Ngai, K. L.; Shinyashiki,
      N. J. Phys. Chem. B 2007, 111, 8197). Furthermore, the same dynamics were found
      in mixtures of two van der Waals glass-formers, which are even simpler systems
      than aqueous mixtures because of the absence of hydrogen bonding. The
      experimental data of these ideal mixtures of van der Waals glass-formers have
      been given a satisfactory theoretical explanation. Since the properties of
      hydrated proteins, aqueous mixtures, and the mixtures of van der Waals liquids
      are similar, we transfer the theoretical understanding gained in the study of the
      last system sequentially to the two other increasingly more complex systems.

PMID- 18318526
TI  - Transport and separation of biomolecular cargo on paramagnetic colloidal
      particles in a magnetic ratchet.
AB  - Paramagnetic particles in a magnetic ratchet potential were transported in
      discrete steps in an aqueous solution on the surface of a magnetic garnet film.
      The proposed technique allows the simultaneously controlled, dispersion-free
      movement of an ensemble of paramagnetic particles across the surface. External
      magnetic modulations were used to transport the particles in a defined direction,
      and a current reversal upon changing the size of the particles was used to
      separate particles having different diameters. Doublets consisting of a larger
      and a smaller particle functionalized with complimentary oligonucleotides and
      bound via Watson-Crick base pairing were separated after melting the double
      stranded DNA.

PMID- 18318527
TI  - Does Forster theory predict the rate of electronic energy transfer for a model
      dyad at low temperature?
AB  - The use of the Forster model to predict the dynamics of resonant electronic
      energy transfer (RET) in a model donor-acceptor dyad (a terphenyl-bridged
      perylene diimide (PDI)-terrylene diimide (TDI) dyad molecule) embedded at low
      temperature in a PMMA matrix is tested against experiment. The relevant
      ingredients involved in the Forster rate for RET, namely electronic coupling,
      spectral overlap, and screening effects, are accounted for in a quantitative
      manner. Electronic couplings are obtained from time-dependent density functional
      theory calculations, and the effect of the PMMA environment is included both on
      the transition densities and on their interaction through the IEFPCM model. We
      find that the presence of the terphenyl bridge induces a slight delocalization of
      the PDI and TDI transition densities over the bridge originating in a 56%
      increase in the coupling and in the breakdown of the dipole-dipole approximation.
      The spectral overlap is determined on the basis of a detailed simulation of the
      homogeneously broadened donor emission and acceptor absorption line shapes
      determined by fitting the single molecule spectra measured at 1.2 K. The
      corresponding distribution of spectral overlap throughout the ensemble is then
      estimated by assuming an uncorrelated inhomogeneous line broadening for the donor
      and acceptor. Combining the calculated electronic couplings and spectral overlaps
      sampled from Monte Carlo realizations of the energetic disorder, we obtain a mean
      RET time (approximately 8 ps) and a distribution in reasonable agreement with
      experiment.

PMID- 18318528
TI  - Supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids:
      synthesis, glucose-surfaced nanoparticles, and recognition with lectin.
AB  - A new class of supramolecular and biomimetic glycopolymer/poly(epsilon
      caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D
      gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA
      PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was
      synthesized by the combination of ring-opening polymerization of epsilon
      caprolactone, supramolecular inclusion reaction, and direct atom transfer radical
      polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA)
      glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion
      complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha
      cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into
      the hydrophobic alpha-CD cavities and their crystallization was completely
      suppressed. Moreover, the self-assembled aggregates from these triblock
      copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded
      polypseudorotaxane core, which changed from spherical micelles to vesicles with
      the decreasing weight fraction of glycopolymer segments. Furthermore, it was
      demonstrated that these triblock copolymers had specific biomolecular recognition
      with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the
      best of our knowledge, this is the first report that describes the synthesis of
      supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids and the
      fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane
      cored aggregates. This hopefully provides a platform for targeted drug delivery
      and for studying the biomolecular recognition between sugar and lectin.

PMID- 18318529
TI  - Reversible bridge-mediated excited-state symmetry breaking in stilbene-linked DNA
      dumbbells.
AB  - The excited-state behavior of synthetic DNA dumbbells possessing
      stilbenedicarboxamide (Sa) linkers separated by short A-tracts or alternating A-T
      base-pair sequences has been investigated by means of fluorescence and transient
      absorption spectroscopy. Electronic excitation of the Sa chromophores results in
      conversion of a locally excited state to a charge-separated state in which one Sa
      is reduced and the other is oxidized. This symmetry-breaking process occurs
      exclusively via a multistep mechanism-hole injection followed by hole transport
      and hole trapping-even at short distances. Rate constants for charge separation
      are strongly distance-dependent at short distances but become less so at longer
      distances. Disruption of the A-tract by inversion of a single A-T base pair
      results in a pronounced decrease in both the rate constant and efficiency of
      charge separation. Hole trapping by Sa is highly reversible, resulting in rapid
      charge recombination that occurs via the reverse of the charge separation
      process: hole detrapping, hole transport, and charge return to regenerate the
      locally excited Sa singlet state. These results differ in several significant
      respects from those previously reported for guanine or stilbenediether as hole
      traps. Neither charge separation nor charge recombination occur via a single-step
      superexchange mechanism, and hole trapping is slower and detrapping faster when
      Sa serves as the electron donor. Both the occurrence of symmetry breaking and
      reversible hole trapping by a shallow trap in a DNA-based system are without
      precedent.

PMID- 18318530
TI  - Activity coefficients at infinite dilution of organic compounds in 1
      (meth)acryloyloxyalkyl-3-methylimidazolium bromide using inverse gas
      chromatography.
AB  - Activity coefficients at infinite dilution, gammainfinity, of organic compounds
      in two new room-temperature ionic liquids (n-methacryloyloxyhexyl-N
      methylimidazolium bromide (C10H17O2MIM)(Br) at 313.15 and 323.15 K and n
      acryloyloxypropyl-N-methylimidazolium bromide(C6H11O2MIM)(Br)) were determined
      using inverse gas chromatography. Phase loading studies of the net retention
      volume per gram of packing as a function of the percent phase loading were used
      to estimate the influence of concurrent retention mechanisms on the accuracy of
      activity coefficients at infinite dilution of solutes in both ionic liquids. It
      was found that most of the solutes were retained largely by partition with a
      small contribution from adsorption and that n-alkanes were retained predominantly
      by interfacial adsorption on ionic liquids studied in this work. The solvation
      characteristics of the two ionic liquids were evaluated using the Abraham
      solvation parameter model.

PMID- 18318531
TI  - Decrease of droplet size of the reverse microemulsion 1-butyl-3-methylimidazolium
      tetrafluoroborate/Triton X-100/cyclohexane by addition of water.
AB  - In the present contribution, results concerning the role of small amounts of
      water in the 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF4)-in
      cyclohexane ionic liquid (IL) reverse microemulsions are reported. Dynamic light
      scattering (DLS) revealed that the size of microemulsion droplets decreased
      remarkably with increasing water content although water is often used as a polar
      component to swell reverse microemulsions. It was thus deduced that the number of
      microemulsion droplets was increased which was confirmed by conductivity
      measurements. The states of dissolved water were investigated by Fourier
      transform IR (FTIR) spectroscopic analysis showing that water molecules mainly
      act as bound water. 1H NMR along with two-dimensional rotating frame nuclear
      Overhauser effect (NOE) experiments (ROESY) further revealed that water molecules
      were mainly located in the periphery of the polar core of the microemulsion
      droplets and behave like a chock being inserted in the palisade layer of the
      droplet. This increased the curvature of the surfactant film at the
      IL/cyclohexane interface and thus led to the decrease of the microemulsion
      droplet size. The order of surfactant molecules arranged in the interface film
      was increased and thus induced a loss of entropy. Isothermal titration
      calorimetry (ITC) indicated that an enthalpy increase compensates for the loss of
      entropy during the process of microstructural transition.

PMID- 18318532
TI  - Photoactive proton conductor: poly(4-vinyl pyridine) gel.
AB  - We describe a hydrogen-bonded poly(4-vinyl pyridine)-based dielectric material,
      in which conductivity can be induced due to the presence of side-chain protonated
      species that form spontaneously when the polymer is dissolved in pyridine. The
      conductivity of the proton conductive gel can be controlled by direct irradiation
      at the proton-transfer center: a reversible change of conductivity was observed
      in response to the on/off switching of 385 nm wavelength radiation. Over most of
      the range of intensities used, the proton conductivity exhibited a bimolecular
      character. We present a model of the protonated pyridine side-chain unit in the
      ground and excited states (DFT level). In the ground state, the protonated
      pyridine moiety has a cyclic, conjugated structure.

PMID- 18318533
TI  - Modulation of the optical response of polyethylene films containing luminescent
      perylene chromophores.
AB  - In this work, two perylene derivatives containing different peripheral alkyl
      chains (i.e., N,N'-bis-(hexyl)perylene-3,4,9,10-tetracarboxyldiimide (ES-PTCDI)
      and N,N'-bis-(2'-ethylhexyl)perylene-3,4,9,10-tetracarboxyldiimide (EE-PTCDI))
      were synthesized and efficiently dispersed at low loadings (from 0.01 to 0.1 wt
      %) into linear low-density polyethylene (LLDPE) by processing in the melt.
      Spectroscopic investigations (UV-vis and fluorescence) combined with quantum
      mechanical studies demonstrated the ability of both chromophores to generate
      aggregates among the planar structure of dyes when dissolved in solution or
      dispersed into LLDPE above a certain concentration. The data acquired for dyes'
      dispersions into the polymer matrix reveal that the optical properties and
      responsiveness to mechanical stimuli are strongly dependent on the compactness of
      perylene aggregates provided by the different molecular structure of dyes. In
      particular, the strong intermolecular aggregates of ES-PTCDI resulted in being
      more resistant toward mechanical stress and less orientable by uniaxial drawing
      along the drawing direction of the film, whereas the less compact and distorted
      supramolecular architecture of EE-PTCDI chromophores provided composite films
      with a remarkable optical response to mechanical solicitations.

PMID- 18318534
TI  - Size dependence of transition temperature in polymer nanowires.
AB  - We studied the effect of changing temperature on the mechanical properties of
      nanosized poly(methyl methacrylate) wires fabricated by two-photon fabrication.
      At around room temperature, the nanowires showed a transition temperature where
      the shear modulus suddenly changed. This transition temperature was observed to
      decrease more than 40 K by decreasing the radius of the nanowires from 450 to 150
      nm. This size is several times larger in nanowires than reported values of
      polymer thin film thickness showing a depression of the glass transition
      temperature.

PMID- 18318535
TI  - Deuterated protein folds obtained directly from unassigned nuclear overhauser
      effect data.
AB  - We demonstrate the feasibility of determining the global fold of a highly
      deuterated protein from unassigned experimental NMR nuclear Overhauser effect
      (NOE) data only. The method relies on the calculation of a spatial configuration
      of covalently unconnected protons-a "cloud"-directly from unassigned distance
      restraints derived from 13C- and 15N-edited NOESY spectra. Each proton in the
      cloud, labeled by its chemical shift and that of the directly bound 13C or 15N,
      is subsequently mapped to specific atoms in the protein. This is achieved via
      graph-theoretical protocols that search for connectivities in graphs that encode
      the structural information within the cloud. The peptidyl HN chain is traced by
      seeking for all possible routes and selecting the one that yields the minimal sum
      of sequential distances. Complete proton identification in the cloud is achieved
      by linking the side-chain protons to proximal main-chain HNs via bipartite graph
      matching. The identified protons automatically yield the NOE assignments, which
      in turn are used for structure calculation with RosettaNMR, a protocol that
      incorporates structural bias derived from protein databases. The method, named
      Sparse-Constraint CLOUDS, was applied to experimental NOESY data on the 58
      residue Z domain of staphylococcal protein A. The generated structures are of
      similar accuracy to those previously reported, which were derived via a
      conventional approach involving a larger NMR data set. Additional tests were
      performed on seven reported protein structures of various folds, using restraint
      lists simulated from the known atomic coordinates.

PMID- 18318536
TI  - Anionic charge is prioritized over geometry in aluminum and magnesium fluoride
      transition state analogs of phosphoryl transfer enzymes.
AB  - Phosphoryl transfer reactions are ubiquitous in biology and metal fluoride
      complexes have played a central role in structural approaches to understanding
      how they are catalyzed. In particular, numerous structures of AlFx-containing
      complexes have been reported to be transition state analogs (TSAs). A survey of
      nucleotide kinases has proposed a correlation between the pH of the
      crystallization solution and the number of coordinated fluorides in the resulting
      aluminum fluoride TSA complexes formed. Enzyme ligands crystallized above pH 7.0
      were attributed to AlF3, whereas those crystallized at or below pH 7.0 were
      assigned as AlF4-. We use 19F NMR to show that for beta-phosphoglucomutase from
      Lactococcus lactis, the pH-switch in fluoride coordination does not derive from
      an AlF4- moiety converting into AlF3. Instead, AlF4- is progressively replaced by
      MgF3- as the pH increases. Hence, the enzyme prioritizes anionic charge at the
      expense of preferred native trigonal geometry over a very broad range of pH. We
      demonstrate similar behavior for two phosphate transfer enzymes that represent
      typical biological phosphate transfer catalysts: an amino acid phosphatase,
      phosphoserine phosphatase from Methanococcus jannaschii and a nucleotide kinase,
      phosphoglycerate kinase from Geobacillus stearothermophilus. Finally, we
      establish that at near-physiological ratios of aluminum to magnesium, aluminum
      can dominate over magnesium in the enzyme-metal fluoride inhibitory TSA
      complexes, and hence is the more likely origin of some of the physiological
      effects of fluoride.

PMID- 18318537
TI  - Oxide and carbide formation at titanium/organic monolayer interfaces.
AB  - X-ray photoelectron spectra (XPS) are reported from a series of buried
      titanium/organic monolayer interfaces accessed through sample delamination in
      ultrahigh vacuum (UHV). Conventional characterization of such buried interfaces
      requires ion-mill depth profiling, an energetic process that frequently destroys
      bonding information by chemically reducing the milled material. In contrast, we
      show that delaminating the samples at the metal/organic interface in vacuum
      yields sharp, nonreduced spectra that allow quantitative analysis of the buried
      interface chemistry. Using this UHV delamination XPS, we examine titanium vapor
      deposited onto a C18 cadmium stearate Langmuir-Blodgett monolayer supported on
      Au, SiO2, or PtO2 substrates. Titanium is widely used as an adhesion layer in
      organic thick film metallization as well as a top metal contact for molecular
      monolayer junctions, where it has been assumed to form a few-atoms-thick Ti
      carbide overlayer. We establish here that under many conditions the titanium
      instead forms a few-nanometers-thick Ti oxide overlayer. Both TiO2 and reduced
      TiOx species exist, with the relative proportion depending on oxygen
      availability. Oxygen is gettered during deposition from the ambient, from the
      organic film, and remarkably, from the substrate itself, producing substrate
      dependent amounts of Ti oxide and Ti carbide "damage". On Au substrates, up to
      20% of the molecular-monolayer carbon formed titanium carbide, SiO2 substrates
      approximately 15%, and PtO2 substrates <5%. Titanium oxide formation is also
      strongly dependent on the deposition rate and chamber pressure.

PMID- 18318538
TI  - Cobalt dinitrosoalkane complexes in the C-H functionalization of olefins.
AB  - The use of cobalt dinitrosoalkane complexes in the C-H functionalization of
      alkenes has been demonstrated. Reaction of a series of alkenes with Me4CpCo(CO)2
      in the presence of NO generates intermediate cobalt dinitrosoalkane complexes
      that can be deprotonated alpha to the nitrosyl group and added to various Michael
      acceptors. The resultant products can then undergo retrocycloaddition reactions
      in the presence of the original alkene to regenerate the starting cobalt
      dinitrosoalkane complex and release the functionalized alkene.

PMID- 18318539
TI  - Synthesis of 7-Epi +-FR900482: an epimer of comparable anti-cancer activity.
AB  - FR900482 is a potent anti-tumor therapeutic that has been investigated as a
      replacement candidate for the clinically useful Mitomycin C. Herein, we report
      synthesis and biological testing of 7-Epi (+)-FR900482, which demonstrates equal
      potency relative to the natural product against several cancer cell lines.
      Highlights of this work include utilization of our palladium-catalyzed DYKAT
      methodology and development of a Polonovski oxidative ring expansion strategy to
      yield this equipotent epimer in 23 linear steps.

PMID- 18318540
TI  - Total synthesis of (+/-)-dysibetaine.
AB  - The marine natural product dysibetaine was synthesized in racemic form from a
      levulinic acid derivative using a convertible isocyanide and an ammonium acetate
      in the Ugi 4-center-3-component condensation reaction.

PMID- 18318541
TI  - Expeditious microwave-assisted thionation with the system PSCl3/H2O/Et3N under
      solvent-free condition.
AB  - A novel thionation protocol for carbonyl compounds, with the system
      PSCl3/H2O/Et3N has been discovered. Clean, rapid, and efficient synthesis of a
      variety of thiocarbonyl compounds such as thioamides, thiolactams, thioketones,
      thioxanthones, and thioacridone can be achieved through this simple and
      convenient method under solventless condition with microwave irradiation.

PMID- 18318542
TI  - Beckmann rearrangement of ketoximes to lactams by triphosphazene catalyst.
AB  - Triphosphazene, 1,3,5-triazo-2,4,6-triphosphorine-2,2,4,4,6,6-chloride (TAPC),
      was found to be an efficient catalyst for the Beckmann rearrangement of
      cyclohexanone oxime and cyclododecanone oxime to epsilon-caprolactam and
      laurolactam, which are raw materials of nylon-6 and nylon-12, respectively.

PMID- 18318543
TI  - Boron trihalide mediated alkyne-aldehyde coupling reactions: a mechanistic
      investigation.
AB  - A boron trihalide mediated alkyne-aldehyde coupling reaction leading to
      stereodefined 1,3,5-triaryl-1,5-dihalo-1,4-pentadienes is described. The study
      led to the discovery of a direct substitution of hydroxyl groups by stereodefined
      alkenyl moieties using alkenylboron dihalides. During the investigation, it was
      also discovered that, at low temperatures, the reaction of BCl3 with alkynes
      produces monovinylboron dichloride rather than the reported divinylboron
      chloride. A modified reaction mechanism for the boron trichloride mediated alkyne
      aldehyde coupling reaction is now proposed. The reaction temperature and mode of
      addition have been found to have dramatic affects on the stereochemistry of the
      diene products.

PMID- 18318544
TI  - Nickel-catalyzed cycloadditions of unsaturated hydrocarbons, aldehydes, and
      ketones.
AB  - The nickel-catalyzed cycloaddition of unsaturated hydrocarbons and carbonyls is
      reported. Diynes and enynes were used as coupling partners. Carbonyl substrates
      include both aldehdyes and ketones. Reactions of diynes and aldehydes afforded
      the [3,3] electrocyclic ring-opened tautomers, rather than pyrans, in high
      yields. The cycloaddition reaction of enynes and aldehydes afforded two distinct
      products. A new carbon-carbon bond is formed, prior to a competitive beta
      hydrogen elimination of a nickel alkoxide, between the carbonyl carbon and either
      one of the carbons of the olefin or the alkyne. The steric hindrance of the enyne
      greatly affected the chemoselectivity of the cycloaddition of enynes and
      aldehydes. In some cases, dihydropyran was also formed. The scope of the
      cycloaddition reaction was expanded to include the coupling of enynes and
      ketones. No beta-hydrogen elimination was observed in cycloaddition reaction of
      enynes and ketones. Instead, C-O bond-forming reductive elimination occurred
      exclusively to afford dihydropyrans in excellent yields. In all cases, complete
      chemoselectivity was observed; only dihydropyrans where the carbonyl carbon forms
      a carbon-carbon bond with a carbon of the olefin, rather than of the alkyne, were
      observed. All cycloaddition reactions occur at room temperature and employ nickel
      catalysts bearing the hindered 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene
      (IPr) or its saturated analogue, 1,3-bis(2,6-diisopropylphenyl)-4,5
      dihydroimidazolin-2-ylidene (SIPr).

PMID- 18318545
TI  - Hypervalent iodine(III)-mediated regioselective N-acylation of 1,3-disubstituted
      thioureas.
AB  - Reaction of asymmetrical 1,3-disubstituted thioureas with diacetoxyiodobenzene
      (DIB) produces regioselectively N-acetylurea in shorter time. Regioselectivity is
      dependent on the pKa's of the amine attached to the thiourea moiety with
      acylation taking place toward the amine having a lower pKa. This is the first
      example of DIB being employed as an N-acetylating agent. A mechanism for this
      novel transformation is also proposed. Mild reaction conditions, shorter reaction
      times, high efficiencies, environmentally benign methods, and facile isolation of
      the desired product make the present methodology a most suitable alternative.

PMID- 18318546
TI  - The vapor-phase phototransposition chemistry of pyridine: deuterium labeling
      studies.
AB  - The six isomeric trideuteriopyridines and the three isomeric
      tetradeuteriopyridines undergo phototransposition upon S0 --> S2 (pi, pi*)
      excitation in the vapor phase at 254 nm. On the basis of the products formed, the
      six trideuteriopyridine isomers can be divided into two triads. Similarly, the
      three isomeric tetradeuteriopyridines also constitute a triad. Irradiation of any
      one member of each triad results in the formation of the other two members of
      that triad. These isomerizations are consistent with a mechanism involving
      photocyclization, nitrogen migration around the five sides of the cyclopentenyl
      ring, and rearomatization.

PMID- 18318547
TI  - General access to the vinca and tacaman alkaloids using a Rh(II)-catalyzed
      cyclization/cycloaddition cascade.
AB  - The total synthesis of several members of the vinca and tacaman classes of indole
      alkaloids has been accomplished. The central step in the synthesis consists of an
      intramolecular [3+2]-cycloaddition reaction of an alpha-diazo indoloamide which
      delivers the pentacyclic skeleton of the natural product in excellent yield. The
      acid lability of the oxabicyclic structure was exploited to establish the trans
      D/E ring fusion of (+/-)-3H-epivincamine (3). Finally, a base induced keto-amide
      ring contraction was utilized to generate the E-ring of the natural product. A
      variation of the cascade sequence of reactions used to synthesize (+/-)-3H
      epivincamine was also employed for the synthesis of the tacaman alkaloids (+/-)
      tacamonine and (+/-)-apotacamine.

PMID- 18318548
TI  - Microfabricated dual sprayer for on-line mass tagging of phosphopeptides.
AB  - Phosphopeptides tagging reactions by dinuclear zinc(II) complexes (1,3-bis[bis(2
      pyridylmethyl)amino]-propan-2-olato dizinc(II)3+, called tag) were performed with
      a dual-channel microsprayer in electrospray ionization mass spectrometry. The
      reaction is first studied ex situ and analyzed with a commercial electrospray
      source. In situ reactions (i.e., inside the Taylor cone) were achieved with a
      dual-channel microsprayer both with the tag synthesized chemically before the
      experiments and with the tag electrogenerated by in situ oxidation of a zinc
      electrode, also used to apply the electrospray current. The device consists of a
      polyimide microchip with two microchannels (20 microm x 50 microm x 1 cm) etched
      on each side of the structure and connecting only at the tip of the microchip. We
      demonstrate here that mixing two solutions with different physicochemical
      properties inside the Taylor cone can be used to selectively tag target
      molecules.

PMID- 18318549
TI  - Sequencing of DNA by free-solution capillary electrophoresis using a genetically
      engineered protein polymer drag-tag.
AB  - We demonstrate the first use of a non-natural, genetically engineered protein
      polymer drag-tag to sequence DNA fragments by end-labeled free-solution
      electrophoresis (ELFSE). Fluorescently labeled DNA fragments resulting from the
      Sanger cycle sequencing reaction were separated by free-solution capillary
      electrophoresis, with much higher resolution and cleaner results than previously
      reported for this technique. With ELFSE, size-based separation of DNA in the
      absence of a sieving matrix is enabled by the end-on attachment of a polymeric
      "drag-tag" that modifies the charge-to-friction ratio of DNA in a size-dependent
      fashion. Progress in ELFSE separations has previously been limited by the lack of
      suitable large, monodisperse drag-tags. To address this problem, we designed,
      constructed, cloned, expressed, and purified a non-natural, genetically
      engineered 127mer protein polymer for use as an ELFSE drag-tag. The Sanger cycle
      sequencing reaction is performed with the drag-tag covalently attached to the
      sequencing primer, a major advance over previous strategies for ELFSE sequencing.
      The electrophoretic separation is diffusion-limited, without significant
      adsorption of the drag-tag to capillary walls. Although the read length (at about
      180 bases) is still short, our results provide evidence that larger protein
      polymer drag-tags, currently under development, could extend the read length of
      ELFSE to more competitive levels. ELFSE offers the possibility of very rapid DNA
      sequencing separations without any of the difficulties associated with viscous
      polymeric sieving networks and hence will be amenable to implementation in
      microchannel and chip-based electrophoresis systems.

PMID- 18318550
TI  - Interfacial tension and spreading coefficient for thin films.
AB  - We present a modified mathematical expression for the interfacial tension of very
      thin films. At large thicknesses the modified expression converges to the classic
      mathematical expression. We use this modified expression to derive an equation
      for the spreading coefficient as a function of film thickness. The spreading
      coefficient equation is then used to calculate the equilibrium thickness of a
      wetting liquid film for a "pancake drop". Our predictions agree with experimental
      data. The study is subjected to systems with van der Waals interactions only.

PMID- 18318551
TI  - Simulations of lipid vesicle adsorption for different lipid mixtures.
AB  - Numerous experimental studies of lipid vesicle adsorption on solid surfaces show
      that electrostatic interactions play an important role for the kinetics and end
      result. The latter can, e.g., be intact vesicles or supported lipid bilayers
      (SLB). Despite an accumulated quite large experimental data base, the
      understanding of the underlying processes is still poor, and mathematical models
      are scarce. We have developed a phenomenological model of a vesicle adsorbing on
      a substrate, where the charge of the surface and the charge and polar state of
      the lipid headgroup can be varied. With physically reasonable assumptions and
      input parameters, we reproduce many key experimental observations, clarify the
      details of some experiments, and give predictions and suggestions for future
      experiments. Specifically, we have investigated the influence of different lipid
      mixtures (different charges of the headgroups) in the vesicle on the outcome of a
      vesicle adsorption event. For different mixtures of zwitterionic lipids with
      positive and negative lipids, we investigated whether the vesicle adsorbs or not,
      and--if it adsorbs--to what extent it gets deformed and when it ruptures
      spontaneously. Diffusion of neutral vesicles on different types of negatively
      charged substrates was also simulated. The mean surface charge density of the
      substrate was varied, including or excluding local fluctuations in the surface
      charge density. The simulations are compared to available experiments. A
      consistent picture of the influence of different lipid mixtures in the vesicle on
      adsorption, and the influence of different types of substrates on vesicle
      diffusion, appear as a result of the simulation data.

PMID- 18318552
TI  - Surface rheology of hydrophobically modified PEG polymers associating with a
      phospholipid monolayer at the air-water interface.
AB  - Surface rheology of irreversibly bound hydrophobically modified poly(ethylene
      glycol) (PEG) polymers (HMPEG) on a dipalmitoylphosphatidylcholine (DPPC)
      monolayer is investigated to determine attributes that may contribute to immune
      recognition. Previously, three comb-graft polymers (HMPEG136-DP3, HMPEG273-DP2.5,
      and HMPEG273-DP5) adsorbed on liposomes were examined for their strength of
      adsorption and protection from complement binding. The data supported an optimal
      ratio between the hydrophilicity of the PEG polymer and the number of hydrophobic
      anchors. The HMPEG polymers have different polymer brush thicknesses (4.2-5.9 nm)
      and levels of cooperativity (2.5-5 hydrophobes). The results indicate that an
      increased viscous force (above 0.25 mN s/m) at the surface may enable the
      polymers to shield liposomes from protein interactions. Similar rheological
      behavior is shown for all polymer architectures at low polymer surface coverage
      (0.5 mg/m2, in the mushroom regime), whereas at high surface coverage (>0.5
      mg/m2, in the brush regime), we observe a structural dependence of the surface
      viscous forces at 40 mN/m. This threshold correlates with a 92% decrease in
      complement protein binding for liposomes coated with 1 mg/m2 HMPEG273-DP5. This
      may suggest that surface viscous forces play a role in reducing complement
      protein binding.

PMID- 18318553
TI  - Silver nanoplates: a highly sensitive material toward inorganic anions.
AB  - This paper demonstrates a simple sensing method to detect inorganic anions by
      silver nanoplates (edge length of approximately 70 nm and thickness of
      approximately 2 nm) in aqueous solution. By this method, the solution system
      containing silver nanoplates shows a high sensitivity on the order of 1 x 10(-6)
      M in detecting halides, phosphate, and thiocyanate ions in water at room
      temperature. The sensitivity could be identified by the shift in the surface
      plasmon resonance (SPR) band in UV-vis spectrum. The selectivity of such a
      sensing system toward various anions was also studied, and it was found that this
      sensing system could distinguish individual anions (e.g., Cl-, Br-, I-, H2PO4-,
      and SCN-) from other anions (e.g., F-, SO42-, CH3COO-, NO3-, and ClO4-) and
      inorganic cations (e.g., Zn2+, Cd2+, and Cu2+) under the given conditions. The
      sensing mechanism was also analyzed. It was proposed that the particle surface
      electron charging, which is mainly determined by the interaction tendency between
      silver atoms and various inorganic anions in water, is responsible for the shift
      in the SPR observed. The need for further studies was finally discussed,
      particularly for systems composed of mixed anions.

PMID- 18318554
TI  - Molecular dynamics simulations for water and ions in protein crystals.
AB  - The spatial and temporal properties of water and ions in bionanoporous materials
      protein crystals-have been investigated using molecular dynamics simulations.
      Three protein crystals are considered systematically with different morphologies
      and chemical topologies: tetragonal lysozyme, orthorhombic lysozyme, and
      tetragonal thermolysin. It is found that the thermal fluctuations of C(alpha)
      atoms in the secondary structures of protein molecules are relatively weak due to
      hydrogen bonding. The solvent-accessible surface area per residue is nearly
      identical in the three protein crystals; the hydrophobic and hydrophilic residues
      in each crystal possess approximately the same solvent-accessible surface area.
      Water distributes heterogeneously and has different local structures within the
      biological nanopores of the three protein crystals. The mobility of water and
      ions in the crystals is enhanced as the porosity increases and also by the
      fluctuations of protein atoms particularly in the two lysozyme crystals.
      Anisotropic diffusion is found preferentially along the pore axis, as
      experimentally observed. The anisotropy of the three crystals increases in the
      order: tetragonal thermolysin < tetragonal lysozyme < orthorhombic lysozyme.

PMID- 18318555
TI  - Probing the conformation of polyelectrolytes in mesoporous silica spheres.
AB  - We report a fluorescence-based approach to probing the conformation of a
      macromolecule, poly(allylamine hydrochloride) (PAH), in bimodal mesoporous silica
      (BMS) particles. The method involves monitoring the fluorescent properties of the
      probe, 1,3,6,8-pyrenetetrasulfonic acid tetrasodium salt (4-PSA), upon
      electrostatic binding to PAH molecules adsorbed in the nanopores of the BMS
      particles. PAH infiltration into the BMS particles, quantified by
      thermogravimetric analysis and visualized by confocal laser scanning microscopy,
      was examined as a function of PAH adsorption time, PAH molecular weight, and the
      sodium chloride (NaCl) concentration and pH of the PAH adsorption solution. The
      conformation of PAH molecules in the nanopores was investigated by incubating the
      PAH-loaded BMS particles in 4-PSA and using the ratio of the excimer to monomer
      emission intensity to discern differences in the PAH conformation in the
      nanopores. Control experiments involving nonporous silica (NS) particles were
      also conducted to determine the extent to which the nanopores within the BMS
      particles influence the degree of PAH adsorption and the conformation of the
      adsorbed PAH molecules. The data indicate that PAH molecules adsorbed in the
      nanopores adopt a more coiled conformation than PAH molecules adsorbed on NS
      particles over a wide range of conditions. Further, the conformation of PAH
      molecules in the nanopores can be tuned by adjusting the NaCl concentration
      and/or pH of the PAH adsorption solution. 4-PSA titration experiments revealed
      that at saturation binding there are ca. 3.8 PAH monomer units per 4-PSA
      molecule. This study provides insights into macromolecule infiltration and
      conformation in nanopores, which are important for the application of mesoporous
      materials in the fields of adsorption/immobilization, catalysis, delivery,
      sensing, separations, and synthesis.

PMID- 18318556
TI  - On the interaction of the anthraquinone barbaloin with negatively charged DMPG
      bilayers.
AB  - Barbaloin is a bioactive glycosilated 1,8-dihydroxyanthraquinone present in
      several exudates from plants, such as Aloe vera, which are used for cosmetic or
      food purposes. It has been shown that barbaloin interacts with DMPG
      (dimyristoylphosphatidylglycerol) model membranes, altering the bilayer structure
      (Alves, D. S.; Perez-Fons, L.; Estepa, A.; Micol, V. Biochem. Pharm. 2004, 68,
      549). Considering that ESR (electron spin resonance) of spin labels is one of the
      best techniques to monitor structural properties at the molecular level, the
      alterations caused by the anthraquinone barbaloin on phospholipid bilayers will
      be discussed here via the ESR signal of phospholipid spin probes intercalated
      into the membranes. In DMPG at high ionic strength (10 mM Hepes pH 7.4 + 100 mM
      NaCl), a system that presents a gel-fluid transition around 23 degrees C, 20 mol
      % barbaloin turns the gel phase more rigid, does not alter much the fluid phase
      packing, but makes the lipid thermal transition less sharp. However, in a low
      salt DMPG dispersion (10 mM Hepes pH 7.4 + 2 mM NaCl), which presents a rather
      complex gel-fluid thermal transition (Lamy-Freund, M. T.; Riske, K. A. Chem.
      Phys. Lipids 2003, 122, 19), barbaloin strongly affects bilayer structural
      properties, both in the gel and fluid phases, extending the transition region to
      much higher temperature values. The position of barbaloin in DMPG bilayers will
      be discussed on the basis of ESR results, in parallel with data from sample
      viscosity, DSC (differential scanning calorimetry), and SAXS (small-angle X-ray
      scattering).

PMID- 18318557
TI  - Photopatterned nanoporosity in polyelectrolyte multilayer films.
AB  - We report on spatial control of nanoporosity in polyelectrolyte multilayer (PEM)
      films using photopatterning and its effects on film optical and adsorption
      properties. Multilayers assembled from poly(acrylic acid-ran-vinylbenzyl
      acrylate) (PAArVBA), a photo-cross-linking polymer, and poly(allylamine
      hydrochloric acid) (PAH) were patterned using ultraviolet light followed by
      immersion in low pH and then neutral pH solutions to induce nanoporosity in
      unexposed regions. Model charged small molecules rhodamine B, fluorescein, and
      propidium iodide and the model protein albumin exhibit increased adsorption to
      nanoporous regions of patterned PEM films as shown by fluorescence microscopy and
      radiolabeling experiments. Films assembled with alternating stacks of
      PAH/poly(sodium-4-styrene sulfonate) (SPS), which do not become nanoporous, and
      stacks of PAH/PAArVBA were patterned to create nanoporous capillary channels.
      Interdigitated channels demonstrated simultaneous, separate wicking of dimethyl
      sulfoxide-solvated fluorescein and rhodamine B. In addition, these heterostack
      structures exhibited patternable Bragg reflectivity of greater than 25% due to
      refractive index differences between the nanoporous and nonporous stacks.
      Finally, the PEM assembly process coupled with photo-cross-linking was used to
      create films with two separate stacked reflective patterns with a doubling in
      reflectivity where patterns overlapped. The combined adsorptive and reflective
      properties of these films hold promise for applications in diagnostic arrays and
      therapeutics delivery.

PMID- 18318558
TI  - Microscopic mechanism of adsorption in cylindrical nanopores with heterogenous
      wall structure.
AB  - We study the microscopic mechanism of adsorption in nanometric cylindrical pores
      with strongly heterogeneous walls using grand canonical Monte Carlo simulations.
      The pore surface structure is modeled by a new lattice-site approach. Each site
      is characterized by two amplitudes--structural and energetic--that locally modify
      the structural and energetic properties of the surface. The amplitudes are
      randomly distributed over the pore wall. We have shown that different structural
      and energetic distribution functions lead to different mechanism of adsorption.
      The energetic site distribution plays the most crucial role in the submonolayer
      region. The structural site distribution modifies the multilayer adsorption. A
      method to analyze the stability of the adsorbed system using static
      susceptibility is proposed. Potential applications in multiscale modeling are
      discussed.

PMID- 18318559
TI  - Gastro-oesophageal reflux disease in Asia : birth of a 'new' disease?
AB  - Gastro-oesophageal reflux disease (GORD) is one of the most common
      gastrointestinal diseases in the Western world and imposes a heavy burden on
      society. Although its prevalence in Asia is much lower, there is evidence that
      this is rapidly rising in Asia. The reported population prevalence of GORD in
      Eastern Asia ranges from 2.5% to 6.7% for at least weekly symptoms of heartburn
      and/or acid regurgitation. In general, Asians tend to have a milder spectrum of
      the disease. Most Asian patients have non-erosive GORD; erosive oesophagitis is
      less commonly seen than in the Western population. Complicated GORD, such as
      oesophageal stricture and Barrett's oesophagus, is seldom encountered. The
      mechanisms of GORD may be different in the Chinese population compared with the
      Western population. Chest pain is the most predominant extra-oesophageal
      manifestation of GORD in China, whereas an association with asthma has been shown
      in Japanese patients. The prevalence of GORD appears to be increasing and
      possible factors for GORD in Asian populations include Helicobacterpylori
      infection, obesity and increasing dietary fat intake. The adoption of a Western
      lifestyle in many developing Asian countries may account for the increasing
      prevalence of GORD. Proton pump inhibitors remain the most effective medical
      treatment for GORD. GORD will undoubtedly be a great challenge to clinicians both
      in primary care and in gastroenterology practice in the Asia-Pacific region in
      the coming years.

PMID- 18318560
TI  - Overview of the management of acute gout and the role of adrenocorticotropic
      hormone.
AB  - It is important to distinguish between therapy used to reduce acute inflammation
      in gout and therapy used to manage hyperuricaemia in patients with chronic gouty
      arthritis. This article discusses treatments for acute gout, emphasizing the use
      of corticotrophin (adrenocorticotropic hormone; ACTH) and the evidence on which
      we base our treatment of acute gout. There are no formal guidelines for the
      treatment of acute gout and only a few randomized controlled trials have been
      conducted to evaluate the efficacy of the various treatments for acute gout. The
      options available for the treatment of acute attacks of gout are NSAIDs,
      colchicine, corticosteroids, corticotropin and intra-articular corticosteroids.
      Most rheumatologists practicing in the US use combination therapy to treat acute
      gout, a practice that merits study. In a patient without complications, NSAIDs
      are the preferred therapy. The most important determinant of therapeutic success
      is not which NSAID is chosen, but rather how soon NSAID therapy is initiated.
      Exciting new research shows that corticotropin acts peripherally by activation of
      the melanocortin type 3 receptor, and this could be responsible, at least in
      part, for its efficacy in acute gout. Hopefully, this will lead to renewed
      interest in corticotropin as a treatment for acute gout.

PMID- 18318561
TI  - Oral colorectal cleansing preparations in adults.
AB  - Bowel preparation has been a much-debated issue for both colonoscopy and for
      colorectal surgery. While bowel preparation for colonoscopy is clearly mandatory
      for optimal intraluminal visualization, bowel preparation for surgery has
      recently been challenged. This review evaluates oral bowel preparation, based on
      evidence in the literature, in order to provide a practical guide for physicians
      and practitioners about oral bowel cleansing preparations in current use for both
      colonoscopy and for colorectal surgery.A MEDLINE search, limited to publications
      in English language, was done through Ovid including articles published from 1966
      to 2007 about bowel preparation using terms 'pre-operative care' and
      'colonoscopy' or 'surgical procedure' associated with 'polyethylene glycol' and
      'sodium phosphate'. The references lists from the identified articles were also
      included in the review. No bowel preparation method meets the ideal criteria for
      bowel cleansing prior to colonoscopy. However, polyethylene glycol-electrolyte
      lavage solution (PEG-ELS) and sodium phosphate are the most commonly used bowel
      preparations before colonoscopy and colon surgery. Both preparations are safely
      used and effective; however, some precautions should be considered, particularly
      with sodium phosphate. In addition, the efficacy of low-volume PEG-ELS can be
      improved by the addition of preparation adjuncts. Timing and dose are important
      considerations regardless of the method used. Mechanical bowel preparation for
      surgery has been questioned, and shown to have no extra benefits and possibly the
      association with increased morbidity. Regardless of the evidence, there are many
      randomized controlled trials showing the lack of benefit of mechanical bowel
      preparation.

PMID- 18318562
TI  - Nelarabine.
AB  - Nelarabine is an anticancer prodrug of arabinofuranosylguanine (ara-G), which is
      metabolized in cells to the cytotoxic metabolite ara-G triphosphate (ara-GTP).
      Ara-GTP competes with deoxyguanosine triphosphate for incorporation into DNA.
      Once incorporated, it inhibits DNA synthesis and leads to high molecular weight
      DNA fragmentation and cell death. In paediatric and adult patients with T-cell
      acute lymphoblastic leukaemia or T-cell lymphoblastic lymphoma, nelarabine
      induced a complete response, with or without complete haematological recovery, in
      approximately one-fifth of patients who had not responded to, or had relapsed
      following treatment with, two or more prior chemotherapy regimens. The median
      overall survival time was 13.1 and 20.6 weeks in paediatric and adult patients,
      with corresponding 1-year survival rates of 14% and 29%. Treatment-emergent
      adverse events were common, but non-haematological events were mostly of mild or
      moderate severity. Neurological events, which may be severe and irreversible,
      were the most likely adverse events to limit treatment.

PMID- 18318563
TI  - Nilotinib.
AB  - Nilotinib is an orally administered BCR-ABL tyrosine kinase inhibitor that has
      shown good clinical efficacy in imatinib-resistant or -intolerant, Philadelphia
      chromosome-positive, chronic myeloid leukaemia (CML) in a phase I/II trial. The
      phase I component of the trial established the dosage regimen used in the phase
      II part of the trial, which included several arms. Three of these arms, or phase
      II trials, evaluated nilotinib in each of the three phases of CML (chronic,
      accelerated or blast crisis).I n the phase II trial in patients with chronic
      phase CML, major cytogenetic response (primary endpoint) was achieved in 48% of
      the 280 patients who received nilotinib and had a follow-up period of > or = 6
      months. Major cytogenetic response rates did not differ between imatinib
      resistant and -intolerant patients, and nilotinib was effective in patients with
      BCR-ABL mutations (except T315I). Haematologic response rate (primary endpoint)
      was 47% in the phase II trial with nilotinib in patients with accelerated-phase
      CML (n = 119). Complete haematologic response was achieved in 26% of patients and
      21% had no evidence of leukaemia or returned to chronic-phase CML. Major
      cytogenetic response, an important secondary endpoint in the trial, occurred in
      29% of patients. Data from the phase II trial in patients with CML in blast
      crisis (n = 135) also showed promising results, with 39% of patients achieving
      haematologic response with nilotinib. Adverse events reported with nilotinib have
      generally been of mild to moderate severity. Grade 3 or 4 neutropenia and
      thrombocytopenia were reported in 29% of patients each.

PMID- 18318566
TI  - Dutasteride: a review of its use in the management of prostate disorders.
AB  - Dutasteride (Avodart), an oral synthetic 4-azasteroid, is a potent, selective,
      irreversible inhibitor of type 1 and type 2 5alpha-reductase (5AR), the enzyme
      that converts testosterone to dihydrotestosterone (DHT) intracellularly. Although
      type 2 5AR predominates, both isoenzymes are overexpressed in prostate tissue in
      benign prostatic hyperplasia (BPH) and at all stages in some prostate cancers.
      Oral dutasteride 0.5 mg once daily is approved for the treatment of moderate to
      severe symptomatic BPH in men with an enlarged prostate to improve symptoms, and
      to reduce the risk of acute urinary retention (AUR) and the need for BPH-related
      surgery.In pivotal 2-year phase III trials, oral dutasteride 0.5 mg once daily
      improved urinary symptoms, decreased total prostate volume (TPV), and reduced the
      risk of AUR and BPH-related surgery in men with moderate to severe symptoms of
      BPH and prostate enlargement. The good efficacy and tolerability of dutasteride
      was maintained for up to 4 years in open-label extension studies. Results of the
      pre-planned, 2-year interim analysis of the CombAT trial showed that the
      combination of dutasteride and tamsulosin was superior to either drug as
      monotherapy in improving BPH-related symptoms, peak urinary flow and BPH-related
      health status. The overall adverse event profile for combination therapy was
      consistent with those reported for both monotherapies. Although drug-related
      adverse events were more frequent with combination therapy versus both
      monotherapies, most did not result in treatment cessation. Dutasteride is being
      investigated for its efficacy in reducing the risk of prostate cancer in at-risk
      men in the 4-year REDUCE study and as treatment to extend the time to progression
      in men with low-risk localized prostate cancer who would otherwise undergo
      watchful waiting in the 3-year REDEEM study. Thus, dutasteride is an effective
      treatment option in patients with moderate to severe symptomatic BPH and
      demonstrable prostatic enlargement, and may have potential to reduce the risk of
      developing biopsy-detectable prostate cancer in at-risk individuals or extending
      the time to progression in low-risk localized prostate cancer.

PMID- 18318567
TI  - Bevacizumab: a review of its use in metastatic colorectal cancer.
AB  - Bevacizumab (Avastin) is a recombinant, humanized monoclonal antibody against
      vascular endothelial growth factor (VEGF) that is used to inhibit VEGF function
      in vascular endothelial cells and thereby inhibit tumour angiogenesis, upon which
      solid tumours depend for growth and metastasis. The addition of bevacizumab to
      fluoropyrimidine-based chemotherapy, with or without irinotecan or oxaliplatin,
      in both the first- and second-line treatment of metastatic colorectal cancer,
      significantly increased median progression-free survival or time to disease
      progression in most randomized controlled trials. Bevacizumab was generally, but
      not always, associated with a survival advantage; in phase III trials, the
      increases in median overall survival attributable to bevacizumab were 4.7 months
      with first-line therapy and 2.1 months with second-line therapy. In some studies,
      patients experienced clinical improvement without an apparent overall survival
      benefit. Bevacizumab had acceptable tolerability, with the majority of adverse
      events being generally mild and clinically manageable. However, from the UK
      National Health Service perspective, bevacizumab was not considered to be cost
      effective in combination with bolus fluorouracil/folinic acid or irinotecan/bolus
      fluorouracil/folinic acid. Additional pharmacoeconomic analyses from different
      perspectives and using clinical data for combinations with the more efficacious
      infusional fluorouracil/folinic acid plus oxaliplatin or irinotecan chemotherapy
      regimens are required. Although cost effectiveness may be a concern, the
      combination of bevacizumab and fluoropyrimidine-based chemotherapy has potential
      in the treatment of metastatic colorectal cancer.

PMID- 18318568
TI  - Zoledronic acid : a review of its use in the management of bone metastases of
      malignancy.
AB  - Zoledronic acid (Zometa), a third-generation amino-bisphosphonate, has been
      approved in the US, the EU and many other countries worldwide for the prevention
      of skeletal-related events in patients with bone metastases of malignancy. In
      several well designed trials, zoledronic acid 4 mg administered as a 15-minute
      infusion every 3-4 weeks was effective in reducing the occurrence of skeletal
      complications in patients with bone metastases secondary to multiple myeloma,
      breast cancer or prostate cancer. Zoledronic acid was as effective as pamidronic
      acid in reducing the occurrence of skeletal complications in patients with
      multiple myeloma or breast cancer. In patients with solid tumours other than
      breast or prostate cancer, zoledronic acid did not show significant clinical
      benefit over placebo in terms of the primary endpoint; however, some benefit of
      therapy in terms of secondary endpoints was observed with zoledronic acid
      relative to placebo. Its efficacy in a broad range of tumours and short infusion
      time (15 minutes) are an advantage over other available bisphosphonates. Modelled
      pharmacoeconomic analyses in patients with breast cancer suggested that
      zoledronic acid therapy is cost effective relative to no therapy with regard to
      the cost per quality-adjusted life-year (QALY) gained; however, results were
      mixed when zoledronic acid was compared with other commonly used bisphosphonates.
      Zoledronic acid is generally well tolerated; the risk of osteonecrosis of the jaw
      may be minimized by adhering to recommendations regarding dental therapy.
      Additional efficacy and economic data are required to definitively position
      zoledronic acid with respect to other bisphosphonates. Nevertheless, available
      clinical data indicate that zoledronic acid is an effective treatment option for
      the management of bone metastases of malignancy.

PMID- 18318569
TI  - Levofloxacin : a review of its use as a high-dose, short-course treatment for
      bacterial infection.
AB  - Levofloxacin (Levaquin) is a fluoroquinolone antibacterial that is the L-isomer
      of ofloxacin. A high-dose (750 mg) short-course (5 days) of once-daily
      levofloxacin is approved for use in the US in the treatment of community-acquired
      pneumonia (CAP), acute bacterial sinusitis (ABS), complicated urinary tract
      infections (UTI) and acute pyelonephritis (AP). The broad spectrum antibacterial
      profile of levofloxacin means that monotherapy is often a possibility in patients
      with CAP at times when other agents may require combination therapy, although
      levofloxacin can be used in combination therapy when necessary. The high-dose,
      short-course levofloxacin regimen maximizes its concentration-dependent
      bactericidal activity and may reduce the potential for resistance to emerge. In
      addition, this regimen lends itself to better compliance because of the shorter
      duration of treatment and the convenient once-daily administration schedule. Oral
      levofloxacin is rapidly absorbed and is bioequivalent to the intravenous
      formulation; importantly, patients can transition between the formulations, which
      results in more options in regards to the treatment regimen and the potential for
      patients with varying degrees of illness to be treated. Levofloxacin has good
      tissue penetration and an adequate concentration can be maintained in the urinary
      tract to treat uropathogens. Levofloxacin is generally well tolerated and has
      good efficacy in the treatment of patients with CAP, ABS, complicated UTI and AP.
      The efficacy and tolerability of levofloxacin 500 mg once daily for 10 days in
      patients with CAP, ABS and UTIs is well established, and the high-dose, short
      course levofloxacin regimen has been shown to be noninferior to the 10-day
      regimen in CAP and ABS, and to have a similar tolerability profile. Similarly,
      the high-dose, short-course levofloxacin regimen is noninferior to ciprofloxacin
      in patients with complicated UTI or AP. Thus, levofloxacin is a valuable
      antimicrobial agent that has activity against a wide range of bacterial
      pathogens; however, its use should be considered carefully so that the potential
      for resistance selection can be minimized and its usefulness in severe infections
      and against a range of penicillin- and macrolide-resistant pathogens can be
      maintained.

PMID- 18318570
TI  - Application of statistical experimental design and multivariate data analysis for
      evaluation of mixtures using cytochrome P4501A induction.
AB  - Cytochrome P4501A (CYP1A) induction was evaluated in the rat hepatoma cell line
      H4IIE as a biomarker of exposure to organic compounds. The 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyl-tetrazoliumbromide assay was performed to assess the viability
      of cells exposed to environmentally relevant concentrations of cadmium. Cadmium
      concentrations greater than approximately 0.7 microM were found to affect cell
      viability. Cells were exposed to environmentally relevant concentrations of
      3,3',4,4'-tetrachlorobiphenyl (PCB 77) or benzo[a]pyrene (BaP) and to
      combinations of PCB 77, BaP, and cadmium based on a statistical experimental
      design. Quantification of CYP1A proteins using Western blot analysis showed that
      both BaP and PCB 77 induced CYP1A in a concentration-dependent manner up to 5
      microM. Response surface modeling for evaluation of the combined effect of
      compounds was conducted using the multivariate regression model projection to
      latent structures (PLS). Analysis of response surface models for the ternary
      mixtures indicated antagonistic interactions between BaP and PCB 77 and a
      possible inhibitory effect of cadmium on PCB 77- induced CYP1A. Use of CYP1A
      induction in the H4IIE cell line with immunodetection of CYP1A proteins, combined
      with the application of response surface design and PLS, is shown to be a
      suitable strategy for evaluating combined effects in pollutant mixtures.

PMID- 18318571
TI  - Human epidermal growth factor receptor 2 testing in breast cancer: 30% versus 10%
      cutoff for immunohistochemistry.

PMID- 18318572
TI  - Lesions of ductal morphology in the prostate.

PMID- 18318574
TI  - Should women with abnormal serum thyroid stimulating hormone undergo screening
      for anemia?

PMID- 18318575
TI  - Illuminating the invisible specimen: Descemet membrane endothelial keratoplasty.

PMID- 18318576
TI  - Immunohistochemistry: then and now.

PMID- 18318577
TI  - Undifferentiated tumor: true identity by immunohistochemistry.
AB  - CONTEXT: "Undifferentiated tumor" refers to a heterogeneous group of neoplasms
      with little or no evidence of differentiation on routine light microscopic
      morphology. OBJECTIVE: To identify the true identity of undifferentiated tumors
      by immunohistochemical analysis. DATA SOURCES: Review of the pertinent literature
      and the authors' experience. CONCLUSIONS: For treatment and prognostic
      evaluation, it is crucial to delineate whether an undifferentiated neoplasm is
      epithelial, mesenchymal, melanocytic, or hematopoietic in nature. Application of
      a screening panel to demonstrate the expression of markers of major lineages is
      fundamental for determination of the broad category of neoplasia. Because poorly
      differentiated carcinomas and in particular sarcomatoid carcinomas are known to
      be heterogeneous in their antigen expression, several epithelial markers in
      combination may be required to establish the carcinomatous nature of tumor. A
      diagnostic misinterpretation as a consequence of occasional aberrant or
      unexpected antigen expression is best avoided by using a broad panel that
      includes both antibodies that are anticipated to be positive and those that are
      expected to be negative. In this treatise, the immunohistochemical dissection of
      undifferentiated tumors on the basis of their morphologic features is outlined,
      supplemented with algorithmic immunohistochemical analysis for each morphologic
      category of small round cell tumors, carcinomatous tumors, sarcomatous (or
      sarcoma-like) tumors, and tumors with histologically overlapping features,
      including hematolymphoid malignancies, melanoma, and sarcomas with epithelioid
      appearance. The utility of several organ- or tissue-specific markers in the
      context of undifferentiated tumors is reviewed.

PMID- 18318578
TI  - Application of immunohistochemistry to breast lesions.
AB  - CONTEXT: Immunohistochemistry has an expanding role in mammary pathology that has
      been facilitated by a growing list of available antibodies and a better
      understanding of biology. OBJECTIVE: To explore the key role of
      immunohistochemistry in guiding adjuvant therapy decisions and sentinel node
      staging in breast cancer, as well as the role of immunohistochemistry as an aid
      to distinguishing usual ductal hyperplasia from atypical ductal hyperplasia/low
      grade carcinoma in situ; subtyping a carcinoma as ductal or lobular, basal or
      luminal; ruling out microinvasion in extensive intraductal carcinoma;
      distinguishing invasive carcinoma from mimics; and establishing that a metastatic
      carcinoma of unknown primary site has originated in the breast. DATA SOURCES:
      Current literature is reviewed, including clinical and pathologic journals.
      CONCLUSIONS: As new, targeted treatments for breast cancer are developed,
      pathologists can expect additional immunohistochemistry applications in the
      future.

PMID- 18318579
TI  - Application of immunohistochemistry to thyroid neoplasms.
AB  - CONTEXT: Thyroid lesions with nodular architecture and follicular pattern of
      growth often pose difficulties in accurate diagnosis during the assessment of
      cytologic and histologic specimens. The diagnosis of follicular neoplasm on
      cytology or of follicular tumor of uncertain malignant potential on histology is
      likely to cause confusion among clinicians and delay effective management of
      these lesions. Occasionally, thyroid tumors represent unusual or metastatic
      lesions and their accurate diagnosis requires immunohistochemical confirmation.
      OBJECTIVE: To review the literature on the applications of immunohistochemistry
      in the differential diagnosis of thyroid tumors. DATA SOURCES: Relevant articles
      indexed in PubMed (National Library of Medicine) between 1976 and 2006.
      CONCLUSIONS: Our review supports the use of ancillary techniques involving a
      panel of antibodies suitable for immunohistochemistry and molecular analysis in
      the assessment of thyroid nodules. These tools can improve diagnostic accuracy
      when combined with standard morphologic criteria.

PMID- 18318580
TI  - Application of immunohistochemistry to cytology.
AB  - CONTEXT: The uses of monoclonal antibodies via immunochemistry have been reported
      frequently within the literature using various methodologies with applications to
      cytology specimens. The direct application of immunochemistry to cytology may
      have a variety of pitfalls that the general pathologist familiar with its
      application to histology may be unaware of when applying it prospectively to
      patient specimens. OBJECTIVE: To review common pitfalls when applying
      immunochemistry to cytology specimens and to suggest approaches to the more
      common differential dilemmas that apply to a variety of cytology specimens that
      could be seen in a general pathology practice. DATA SOURCES: The authors' own
      experiences of applying immunochemistry to cytopathology specimens within an
      academic setting along with supportive data from the literature. CONCLUSIONS:
      Immunochemistry can be used to increase the predictability of a cytology
      diagnosis if care is taken with the cytology sample preparation methodology and
      there is judicious use of select monoclonal antibody panels to support a specific
      cytology diagnosis. Up-to-date evidence-based antibody databases should be used
      when selecting antibody panels.

PMID- 18318581
TI  - Application of immunohistochemistry to the diagnosis of primary and metastatic
      carcinoma to the lung.
AB  - CONTEXT: Immunohistochemistry is a very valuable and often used tool in the
      differential diagnosis of lung carcinomas whether primary or secondary to the
      lung. The most useful application is in distinguishing primary lung tumors from
      metastatic tumors to the lung from common sites (colon, breast, prostate,
      pancreas, stomach, kidney, bladder, ovaries, and uterus). Immunohistochemistry
      also aids in the separation of small cell carcinoma from non-small cell carcinoma
      and carcinoids particularly in small biopsy specimens limited by artifact.
      Although there is no "lung-specific tumor marker," with the help of a relatively
      restricted marker, thyroid transcription factor 1, it is possible to separate a
      lung primary from a metastasis with a reasonable degree of certainty. Another
      lung-specific marker on the horizon is napsin A, which appears to complement
      thyroid transcription factor 1 in defining a lung primary. OBJECTIVE: To present
      a practical review and to critique commonly used markers in the differential
      diagnosis of lung neoplasms and to list valuable immunohistochemical prognostic
      markers that the pathologist is called on to perform and interpret. DATA SOURCES:
      A comprehensive PubMed data search and personal practical experience.
      CONCLUSIONS: With a panel of immunohistochemical markers, it is possible to
      distinguish or narrow down most lung neoplasms and separate them into meaningful
      therapeutic categories. In the future as more proteomic and genomic data surface,
      immunohistochemical markers to newly discovered antigens may become a routine
      part of prognostication.

PMID- 18318582
TI  - Application of immunohistochemistry to the diagnosis of malignant mesothelioma.
AB  - CONTEXT: The diagnosis of malignant mesothelioma (MM) is rendered with the aid of
      immunohistochemistry to demonstrate the presence of "mesothelial," "epithelial,"
      or "sarcomatous" differentiation. Antibody panels that have been proposed for the
      distinction between MM and other neoplasms usually include 2 or more epithelial
      markers used to exclude the diagnosis of a carcinoma, such as monoclonal and
      polyclonal carcinoembryonic antigen, Ber-EP4, B72.3, CD15, MOC-31, thyroid
      transcription factor 1, BG8, and others, and 2 or more mesothelial markers used
      to confirm the diagnosis of MM, such as cytokeratin 5/6, calretinin, HBME-1,
      thrombomodulin, WT-1, mesothelin, D2-40, and podoplanin. In general, most
      antibody panels provide excellent sensitivity and specificity for the
      differential diagnosis between MM epithelial variant and adenocarcinoma,
      particularly of lung origin. However, the accuracy of these markers is lower for
      the diagnosis of sarcomatous MM and for the differential diagnosis between MM and
      squamous cell carcinoma and carcinomas of renal, ovarian, and other origin.
      OBJECTIVE: To identify optimal antibody panels for the diagnosis of MM. DATA
      SOURCES: Literature review to determine how many and which mesothelial and
      epithelial markers need to be included in differential diagnosis antibody panels.
      CONCLUSIONS: Various antibody panels have been recommended for the diagnosis of
      MM, with no overall consensus about how many and which markers should be used. A
      recent study with Bayesian statistics has demonstrated that the use of many
      markers does not provide higher diagnostic accuracy than the use of selected
      single antibodies or various combinations of only 2 markers. There is a need for
      the development of evidence-based or consensus-based guidelines for the diagnosis
      of MM in different differential diagnosis situations.

PMID- 18318583
TI  - Application of immunohistochemistry to gynecologic pathology.
AB  - CONTEXT: A large variety of tumors and lesions arise in the female genital tract.
      Although the majority of these can be correctly recognized on routine hematoxylin
      eosin-stained slides, occasional cases present a diagnostic challenge.
      Immunohistochemical stains are extremely useful in resolving many of these
      problematic cases. As the knowledge in this area is constantly expanding, it is
      useful to have this updated information in a review form for easy access.
      OBJECTIVE: To present our current knowledge of immunohistochemistry of the
      lesions of the female genital tract in a readily accessible form. DATA SOURCES:
      The review is based on previously published articles on this topic. CONCLUSIONS:
      Immunohistochemical stains help in reaching a conclusive diagnosis in a variety
      of problematic lesions seen in gynecologic pathology. As in any other system,
      immunohistochemical findings need to be interpreted in light of the clinical
      history and morphologic findings.

PMID- 18318584
TI  - Application of immunohistochemistry to infections.
AB  - CONTEXT: Pathologists play an important role in the diagnosis or exclusion of
      infectious diseases. Traditionally, the diagnosis of infectious diseases rely on
      serologic assays and cultures. Serologic results may be difficult to interpret in
      the setting of immunosuppression, fresh tissue is not always available for
      culture, and culture of fastidious pathogens can be difficult and may take weeks
      or months to yield a result. Although some microorganisms or their cytopathic
      effects may be readily identifiable on routine and/or histochemical stains, often
      these changes are not specific or are sparse in the sample evaluated. In these
      cases, additional immunohistochemical stains are often needed to establish the
      diagnosis of infection. OBJECTIVE: To review the current value and limitations of
      the use of immunohistochemistry in the diagnosis of infectious diseases in
      formalin-fixed tissue samples. DATA SOURCES: Literature in Medline and the
      authors' own experience. CONCLUSIONS: Immunohistochemistry has proven to be a
      useful tool in the diagnosis of infectious diseases in tissue samples.
      Immunohistochemistry is especially useful in the identification of microorganisms
      that are present in low numbers, stain poorly, are fastidious to grow, are
      noncultivable, or exhibit an atypical morphology. Finally, it is important to
      remember that there may be widespread occurrence of common antigens among
      bacteria and pathogenic fungi and both monoclonal and polyclonal antibodies must
      be tested for possible cross-reactivity with other organisms.

PMID- 18318585
TI  - Application of immunohistochemistry to the genitourinary system (prostate,
      urinary bladder, testis, and kidney).
AB  - CONTEXT: The variety of morphologic patterns of different entities of the
      genitourinary tract can present a diagnostic dilemma for the pathologist. This is
      especially true in cases of mimics of cancer, a cancer of unknown primary, or
      poorly differentiated tumors, in which it is hard to assign histogenesis needed
      to plan the correct therapy for the patient. Immunohistochemistry offers a better
      capacity than hematoxylin-eosin staining alone to differentiate human tissue
      types. Also, in the past decades, several techniques had been developed to
      differentiate between benign and malignant processes with morphologic overlap. By
      using immunohistochemistry in selected cases, the rate of false-negative and
      false-positive diagnoses can be reduced, and some patients are afforded the
      opportunity to get more specific or effective therapy as a result. OBJECTIVE: For
      each subgroup of genitourinary system tumors, common diagnostic problems are
      reviewed, and immunohistochemical markers useful in addressing these problems are
      discussed, along with expected patterns of immunoreactivity. DATA SOURCES: The
      pertinent literature, with focus on immunohistochemical staining of tumors of the
      genitourinary tract. CONCLUSIONS: The addition of immunohistochemistry to the
      diagnostic armamentarium for genitourinary pathologic diagnosis has increased the
      sensitivity and specificity of diagnoses and aided in the selection of optional
      therapeutic regimens in selected cases.

PMID- 18318586
TI  - Application of immunohistochemistry in the diagnosis of non-Hodgkin and Hodgkin
      lymphoma.
AB  - CONTEXT: Beginning with the immunologic classifications of Lukes and Collins and
      Kiel and culminating in the Revised European-American Lymphoma and World Health
      Organization classifications, the diagnosis of lymphoid tumors relies heavily on
      the determination of cell lineage, maturation, and function, based on antigen
      expression in addition to morphology and clinical features. Technologic advances
      in immunology, antibody production, genetic analysis, cloning, and the
      identification of new genes and proteins by microarray and proteomics have
      provided pathologists with many antibodies to use in routine diagnosis.
      OBJECTIVE: To provide guidance to the practicing pathologist in the appropriate
      selection of an antibody panel for the diagnosis of lymphoma based on morphology
      and relevant clinical data and to avoid pitfalls in the interpretation of
      immunohistochemical data. Attention is given to some of the newer antibodies,
      particularly against transcription factors, that are diagnostically and
      prognostically useful. DATA SOURCES: The information presented in this article is
      based on review of the literature using the OVID database (Ovid MEDLINE 1950 to
      present with daily update) and 20 years of experience in diagnostic
      hematopathology. CONCLUSIONS: Immunophenotyping is required for the diagnosis and
      classification of lymphoid malignancies. Many paraffin-reactive antibodies are
      available to the pathologist but most are not specific. To avoid diagnostic
      pitfalls, interpretation of marker studies must be based on a panel and knowledge
      of a particular antigen's expression in normal, reactive, and neoplastic
      conditions.

PMID- 18318587
TI  - Acute leukemia immunohistochemistry: a systematic diagnostic approach.
AB  - CONTEXT: The diagnosis and classification of leukemia is becoming increasingly
      complex. Current classification schemes incorporate morphologic features,
      immunophenotype, molecular genetics, and clinical data to specifically categorize
      leukemias into various subtypes. Although sophisticated methodologies are
      frequently used to detect characteristic features conferring diagnostic,
      prognostic, or therapeutic implications, a thorough microscopic examination
      remains essential to the pathologic evaluation. Detailed blast immunophenotyping
      can be performed with lineage- and maturation-specific markers. Although no one
      marker is pathognomonic for one malignancy, a well-chosen panel of antibodies can
      efficiently aid the diagnosis and classification of acute leukemias. OBJECTIVE:
      To review important developments from recent and historical literature. General
      immunohistochemical staining patterns of the most commonly encountered lymphoid
      and myeloid leukemias are emphasized. The goal is to discuss the immunostaining
      of acute leukemias when flow cytometry and genetic studies are not available.
      DATA SOURCES: A comprehensive review was performed of the relevant literature
      indexed in PubMed (National Library of Medicine) and referenced medical texts.
      Additional references were identified in the reviewed manuscripts. CONCLUSIONS:
      Immunophenotyping of blasts using an immunohistochemical approach to lymphoid and
      myeloid malignancies is presented. Initial and subsequent additional antibody
      panels are suggested to confirm or exclude each possibility in the differential
      diagnosis and a general strategy for diagnostic evaluation is discussed. Although
      the use of immunohistochemistry alone is limited and evaluation by flow cytometry
      and genetic studies is highly recommended, unavoidable situations requiring
      analysis of formalin-fixed tissue specimens arise. When performed in an optimized
      laboratory and combined with a careful morphologic examination, the
      immunohistochemical approach represents a useful laboratory tool for classifying
      various leukemias.

PMID- 18318588
TI  - Application of immunohistochemistry to soft tissue neoplasms.
AB  - CONTEXT: Soft tissue tumors are composed of numerous and complex diagnostic
      entities. Because of this complexity and the recognition of an intermediate
      malignancy category including some tumors with a deceptively bland histologic
      appearance, soft tissue tumors may represent a major diagnostic challenge to the
      general practicing pathologist. OBJECTIVE: To correctly diagnose soft tissue
      tumors with the ancillary use of immunohistochemistry. DATA SOURCES: Review of
      the current literature with emphasis on those tumors for which
      immunohistochemistry has proven to be particularly useful. CONCLUSIONS:
      Immunohistochemistry plays an important role in the diagnosis of soft tissue
      tumors. One of its major utilities is to correctly identify a tumor as being of
      mesenchymal or nonmesenchymal origin. Once mesenchymal origin has been
      established, histologic subtyping according to specific cell lineage may be
      achieved with the use of lineage-specific markers. Tumors of uncertain cell
      lineage and tumors with primitive small round cell morphology are often
      characterized by a unique immunohistochemical phenotype. In this group of tumors,
      immunohistochemistry is most widely applied and is of greatest value. Despite the
      rapid development of molecular genetic techniques, immunohistochemistry still
      remains the most important diagnostic tool in the diagnosis of soft tissue tumors
      aside from recognition of morphologic features and clinical correlation.

PMID- 18318589
TI  - Application of immunohistochemistry to liver and gastrointestinal neoplasms:
      liver, stomach, colon, and pancreas.
AB  - CONTEXT: Immunohistochemistry has become an integral component of the practice of
      pathology. Newer antibodies allow for increasingly precise diagnoses for tumors
      that previously could not be easily identified. Recently, immunohistochemical
      evaluations have begun to allow pathologists to actively assist in determining
      prognosis and even in selecting therapies. OBJECTIVE: To summarize the usefulness
      of currently available immunostains for the study of liver and gastrointestinal
      system neoplasms and to make recommendations for panels of immunostains that can
      be particularly helpful. DATA SOURCES: Information has been collected from recent
      literature as well as from personal experience and practice. CONCLUSIONS: Many
      immunostains are now available for the practicing pathologist that allow for
      increasing accuracy in diagnosis of liver and gastrointestinal tract neoplasms.
      Panels of immunostains can be used to differentiate between various tumors and
      also to identify site of origin in the case of a metastatic neoplasm.
      Immunostains that allow for prognostic determinations and for guidance in the
      selection of chemotherapeutic agents can also be used by pathologists to assist
      in the management of patients with malignant tumors affecting the liver and
      gastrointestinal tract.

PMID- 18318590
TI  - The differential diagnosis of central nervous system tumors: a critical
      examination of some recent immunohistochemical applications.
AB  - CONTEXT: As we write, novel antibodies that may well alter the routine practice
      of surgical neuropathology are in development, characterization, and the early
      stages of clinical use. These will be used for purposes of tumor
      subclassification, as prognostic markers, as identifiers of potential therapeutic
      targets, and as predictors of treatment response. OBJECTIVE: To provide for
      nonspecialists a critical assessment of the peer-reviewed literature (necessarily
      colored by our own experience) as it pertains to several immunohistochemical
      reagents that have been recently forwarded as adjuncts to the histologic typing
      of central nervous system tumors. DATA SOURCES: We address in these pages only
      antibodies that are commercially available, that have been the subjects of
      multiple published series, and that we have had occasion to use in the course of
      everyday problem solving. CONCLUSIONS: Discussion concentrates on the use of 4
      antibodies: BAF47 in the diagnosis of atypical teratoid/ rhabdoid tumor, OCT4 in
      intracranial germinoma, beta-catenin in craniopharyngioma, and NeuN as a marker
      of neuronal differentiation in neuroepithelial neoplasms.

PMID- 18318592
TI  - How to deal with lipophilic and volatile organic substances in microtiter plate
      assays.
AB  - Microtiter plate-based assays are a promising technique for toxicity assessment
      of substances. Chemicals with physicochemical properties such as high volatility
      and/or high lipophilicity, however, can be lost from the exposure solution during
      an experiment, so that exposure concentrations are not consistent. The aim of the
      present study was to determine and reduce the proportion of the reference
      compounds phenanthrene and phenanthridine lost during exposure in the zebra fish
      (Danio rerio) embryo test regime. It could be shown that under the standard
      exposure regime (48 h), the concentration of phenanthrene decreased strongly, by
      more than 99%, whereas that of phenanthridine decreased by 17% during a 48-h
      experiment. After modifications to the microtiter plate exposure regime, the
      phenanthrene concentration showed a decrease of only 40%, while the
      phenanthridine concentration remained unchanged. The major processes of substance
      loss could be assigned to accumulations of these substances into the glue of
      commercially available adhesive foils and the polystyrene walls of the microtiter
      plates. Furthermore, by investigating the sorption capacity of different
      plastics, it was found that the phenanthrene concentration decreased less when
      using a plexiglass specimen (28%) compared with the same-sized polystyrene
      specimen (94%). Moreover, it was found, for a constant exposure regime, that
      concentration profiles of different phenanthrene concentrations in the microtiter
      plate assay during an experiment were similar. A mathematical method is proposed
      to predict concentration profiles in an exposure solution by scaling a determined
      profile.

PMID- 18318593
TI  - Toxicodynamic assumptions in ecotoxicological hazard models.
AB  - Existing toxicokinetic and toxicodynamic models and dynamic formulations of
      popular ecotoxicological concepts (e.g., the critical body residue concept) are
      examined. Their underlying assumptions about speed of recovery and thresholds are
      clarified, and a rigorous mathematical treatment shows that they can all be
      placed within a unifying framework. Such analysis aids in the selection of
      appropriate ecotoxicological models.

PMID- 18318594
TI  - Could an open-source clinical trial data-management system be what we have all
      been looking for?

PMID- 18318595
TI  - Late-life cardiac interventions and the treatment imperative.

PMID- 18318596
TI  - An antibiotic-responsive mouse model of fulminant ulcerative colitis.
AB  - BACKGROUND: The constellation of human inflammatory bowel disease (IBD) includes
      ulcerative colitis and Crohn's disease, which both display a wide spectrum in the
      severity of pathology. One theory is that multiple genetic hits to the host
      immune system may contribute to the susceptibility and severity of IBD. However,
      experimental proof of this concept is still lacking. Several genetic mouse models
      that each recapitulate some aspects of human IBD have utilized a single gene
      defect to induce colitis. However, none have produced pathology clearly
      distinguishable as either ulcerative colitis or Crohn's disease, in part because
      none of them reproduce the most severe forms of disease that are observed in
      human patients. This lack of severe IBD models has posed a challenge for research
      into pathogenic mechanisms and development of new treatments. We hypothesized
      that multiple genetic hits to the regulatory machinery that normally inhibits
      immune activation in the intestine would generate more severe, reproducible
      pathology that would mimic either ulcerative colitis or Crohn's disease. METHODS
      AND FINDINGS: We generated a novel mouse line (dnKO) that possessed defects in
      both TGFbetaRII and IL-10R2 signaling. These mice rapidly and reproducibly
      developed a disease resembling fulminant human ulcerative colitis that was quite
      distinct from the much longer and more variable course of pathology observed
      previously in mice possessing only single defects. Pathogenesis was driven by
      uncontrolled production of proinflammatory cytokines resulting in large part from
      T cell activation. The disease process could be significantly ameliorated by
      administration of antibodies against IFNgamma and TNFalpha and was completely
      inhibited by a combination of broad-spectrum antibiotics. CONCLUSIONS: Here, we
      develop to our knowledge the first mouse model of fulminant ulcerative colitis by
      combining multiple genetic hits in immune regulation and demonstrate that the
      resulting disease is sensitive to both anticytokine therapy and broad-spectrum
      antibiotics. These findings indicated the IL-10 and TGFbeta pathways synergize to
      inhibit microbially induced production of proinflammatory cytokines, including
      IFNgamma and TNFalpha, which are known to play a role in the pathogenesis of
      human ulcerative colitis. Our findings also provide evidence that broad-spectrum
      antibiotics may have an application in the treatment of patients with ulcerative
      colitis. This model system will be useful in the future to explore the microbial
      factors that induce immune activation and characterize how these interactions
      produce disease.

PMID- 18318597
TI  - Alcohol intake and blood pressure: a systematic review implementing a Mendelian
      randomization approach.
AB  - BACKGROUND: Alcohol has been reported to be a common and modifiable risk factor
      for hypertension. However, observational studies are subject to confounding by
      other behavioural and sociodemographic factors, while clinical trials are
      difficult to implement and have limited follow-up time. Mendelian randomization
      can provide robust evidence on the nature of this association by use of a common
      polymorphism in aldehyde dehydrogenase 2 (ALDH2) as a surrogate for measuring
      alcohol consumption. ALDH2 encodes a major enzyme involved in alcohol metabolism.
      Individuals homozygous for the null variant (*2*2) experience adverse symptoms
      when drinking alcohol and consequently drink considerably less alcohol than wild
      type homozygotes (*1*1) or heterozygotes. We hypothesise that this polymorphism
      may influence the risk of hypertension by affecting alcohol drinking behaviour.
      METHODS AND FINDINGS: We carried out fixed effect meta-analyses of the ALDH2
      genotype with blood pressure (five studies, n = 7,658) and hypertension (three
      studies, n = 4,219) using studies identified via systematic review. In males, we
      obtained an overall odds ratio of 2.42 (95% confidence interval [CI] 1.66-3.55, p
      = 4.8 x 10(-6)) for hypertension comparing *1*1 with *2*2 homozygotes and an odds
      ratio of 1.72 (95% CI 1.17-2.52, p = 0.006) comparing heterozygotes (surrogate
      for moderate drinkers) with *2*2 homozygotes. Systolic blood pressure was 7.44
      mmHg (95% CI 5.39-9.49, p = 1.1 x 10(-12)) greater among *1*1 than among *2*2
      homozygotes, and 4.24 mmHg (95% CI 2.18-6.31, p = 0.00005) greater among
      heterozygotes than among *2*2 homozygotes. CONCLUSIONS: These findings support
      the hypothesis that alcohol intake has a marked effect on blood pressure and the
      risk of hypertension.

PMID- 18318598
TI  - Aberrant mucin assembly in mice causes endoplasmic reticulum stress and
      spontaneous inflammation resembling ulcerative colitis.
AB  - BACKGROUND: MUC2 mucin produced by intestinal goblet cells is the major component
      of the intestinal mucus barrier. The inflammatory bowel disease ulcerative
      colitis is characterized by depleted goblet cells and a reduced mucus layer, but
      the aetiology remains obscure. In this study we used random mutagenesis to
      produce two murine models of inflammatory bowel disease, characterised the basis
      and nature of the inflammation in these mice, and compared the pathology with
      human ulcerative colitis. METHODS AND FINDINGS: By murine N-ethyl-N-nitrosourea
      mutagenesis we identified two distinct noncomplementing missense mutations in
      Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains
      developed mild spontaneous distal intestinal inflammation by 6 wk (histological
      colitis scores versus wild-type mice, p < 0.01) and chronic diarrhoea. Monitoring
      over 300 mice of each strain demonstrated that 25% and 40% of each strain,
      respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice
      showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a
      diminished mucus barrier, and increased susceptibility to colitis induced by a
      luminal toxin. Enhanced local production of IL-1beta, TNF-alpha, and IFN-gamma
      was seen in the distal colon, and intestinal permeability increased 2-fold. The
      number of leukocytes within mesenteric lymph nodes increased 5-fold and
      leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-gamma, TNF
      alpha, and IL-13). This pathology was accompanied by accumulation of the Muc2
      precursor and ultrastructural and biochemical evidence of endoplasmic reticulum
      (ER) stress in goblet cells, activation of the unfolded protein response, and
      altered intestinal expression of genes involved in ER stress, inflammation,
      apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains
      in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress.
      In human ulcerative colitis we demonstrate similar accumulation of
      nonglycosylated MUC2 precursor in goblet cells together with ultrastructural and
      biochemical evidence of ER stress even in noninflamed intestinal tissue. Although
      our study demonstrates that mucin misfolding and ER stress initiate colitis in
      mice, it does not ascertain the genetic or environmental drivers of ER stress in
      human colitis. CONCLUSIONS: Characterisation of the mouse models we created and
      comparison with human disease suggest that ER stress-related mucin depletion
      could be a fundamental component of the pathogenesis of human colitis and that
      clinical studies combining genetics, ER stress-related pathology and relevant
      environmental epidemiology are warranted.

PMID- 18318599
TI  - Idiopathic pulmonary fibrosis: aberrant recapitulation of developmental programs?

PMID- 18318600
TI  - Assessing evidence for a pervasive alteration in tropical tree communities.
AB  - In Amazonian tropical forests, recent studies have reported increases in
      aboveground biomass and in primary productivity, as well as shifts in plant
      species composition favouring fast-growing species over slow-growing ones. This
      pervasive alteration of mature tropical forests was attributed to global
      environmental change, such as an increase in atmospheric CO2 concentration,
      nutrient deposition, temperature, drought frequency, and/or irradiance. We used
      standardized, repeated measurements of over 2 million trees in ten large (16-52
      ha each) forest plots on three continents to evaluate the generality of these
      findings across tropical forests. Aboveground biomass increased at seven of our
      ten plots, significantly so at four plots, and showed a large decrease at a
      single plot. Carbon accumulation pooled across sites was significant (+0.24 MgC
      ha(-1) y(-1), 95% confidence intervals [0.07, 0.39] MgC ha(-1) y(-1)), but lower
      than reported previously for Amazonia. At three sites for which we had data for
      multiple census intervals, we found no concerted increase in biomass gain, in
      conflict with the increased productivity hypothesis. Over all ten plots, the
      fastest-growing quartile of species gained biomass (+0.33 [0.09, 0.55] % y(-1))
      compared with the tree community as a whole (+0.15 % y(-1)); however, this
      significant trend was due to a single plot. Biomass of slow-growing species
      increased significantly when calculated over all plots (+0.21 [0.02, 0.37] % y(
      1)), and in half of our plots when calculated individually. Our results do not
      support the hypothesis that fast-growing species are consistently increasing in
      dominance in tropical tree communities. Instead, they suggest that our plots may
      be simultaneously recovering from past disturbances and affected by changes in
      resource availability. More long-term studies are necessary to clarify the
      contribution of global change to the functioning of tropical forests.

PMID- 18318601
TI  - Insights into mad2 regulation in the spindle checkpoint revealed by the crystal
      structure of the symmetric mad2 dimer.
AB  - In response to misaligned sister chromatids during mitosis, the spindle
      checkpoint protein Mad2 inhibits the anaphase-promoting complex or cyclosome
      (APC/C) through binding to its mitotic activator Cdc20, thus delaying anaphase
      onset. Mad1, an upstream regulator of Mad2, forms a tight core complex with Mad2
      and facilitates Mad2 binding to Cdc20. In the absence of its binding proteins,
      free Mad2 has two natively folded conformers, termed N1-Mad2/open-Mad2 (O-Mad2)
      and N2-Mad2/closed Mad2 (C-Mad2), with C-Mad2 being more active in APC/C(Cdc20)
      inhibition. Here, we show that whereas O-Mad2 is monomeric, C-Mad2 forms either
      symmetric C-Mad2-C-Mad2 (C-C) or asymmetric O-Mad2-C-Mad2 (O-C) dimers. We also
      report the crystal structure of the symmetric C-C Mad2 dimer, revealing the basis
      for the ability of unliganded C-Mad2, but not O-Mad2 or liganded C-Mad2, to form
      symmetric dimers. A Mad2 mutant that predominantly forms the C-C dimer is
      functional in vitro and in living cells. Finally, the Mad1-Mad2 core complex
      facilitates the conversion of O-Mad2 to C-Mad2 in vitro. Collectively, our
      results establish the existence of a symmetric Mad2 dimer and provide insights
      into Mad1-assisted conformational activation of Mad2 in the spindle checkpoint.

PMID- 18318602
TI  - Effects of selection for honey bee worker reproduction on foraging traits.
AB  - The "reproductive ground plan" hypothesis (RGPH) proposes that reproductive
      division of labour in social insects had its antecedents in the ancient gene
      regulatory networks that evolved to regulate the foraging and reproductive phases
      of their solitary ancestors. Thus, queens express traits that are characteristic
      of the reproductive phase of solitary insects, whereas workers express traits
      characteristic of the foraging phase. The RGPH has also been extended to help
      understand the regulation of age polyethism within the worker caste and more
      recently to explain differences in the foraging specialisations of individual
      honey bee workers. Foragers that specialise in collecting proteinaceous pollen
      are hypothesised to have higher reproductive potential than individuals that
      preferentially forage for nectar because genes that were ancestrally associated
      with the reproductive phase are active. We investigated the links between honey
      bee worker foraging behaviour and reproductive traits by comparing the foraging
      preferences of a line of workers that has been selected for high rates of worker
      reproduction with the preferences of wild-type bees. We show that while selection
      for reproductive behaviour in workers has not altered foraging preferences, the
      age at onset of foraging of our selected line has been increased. Our findings
      therefore support the hypothesis that age polyethism is related to the
      reproductive ground plan, but they cast doubt on recent suggestions that foraging
      preferences and reproductive traits are pleiotropically linked.

PMID- 18318603
TI  - Functional adaptation of a plant receptor-kinase paved the way for the evolution
      of intracellular root symbioses with bacteria.
AB  - Nitrogen-fixing root nodule symbioses (RNS) occur in two major forms-Actinorhiza
      and legume-rhizobium symbiosis-which differ in bacterial partner, intracellular
      infection pattern, and morphogenesis. The phylogenetic restriction of nodulation
      to eurosid angiosperms indicates a common and recent evolutionary invention, but
      the molecular steps involved are still obscure. In legumes, at least seven genes
      including the symbiosis receptor-kinase gene SYMRK-are essential for the
      interaction with rhizobia bacteria and for the Arbuscular Mycorrhiza (AM)
      symbiosis with phosphate-acquiring fungi, which is widespread in occurrence and
      believed to date back to the earliest land plants. We show that SYMRK is also
      required for Actinorhiza symbiosis of the cucurbit Datisca glomerata with
      actinobacteria of the genus Frankia, revealing a common genetic basis for both
      forms of RNS. We found that SYMRK exists in at least three different structural
      versions, of which the shorter forms from rice and tomato are sufficient for AM,
      but not for functional endosymbiosis with bacteria in the legume Lotus japonicus.
      Our data support the idea that SYMRK sequence evolution was involved in the
      recruitment of a pre-existing signalling network from AM, paving the way for the
      evolution of intracellular root symbioses with nitrogen-fixing bacteria.

PMID- 18318604
TI  - Face adaptation does not improve performance on search or discrimination tasks.
AB  - The face adaptation effect, as described by M. A. Webster and O. H. MacLin
      (1999), is a robust perceptual shift in the appearance of faces after a brief
      adaptation period. For example, prolonged exposure to Asian faces causes a
      Eurasian face to appear distinctly Caucasian. This adaptation effect has been
      documented for general configural effects, as well as for the facial properties
      of gender, ethnicity, expression, and identity. We began by replicating the
      finding that adaptation to ethnicity, gender, and a combination of both features
      induces selective shifts in category appearance. We then investigated whether
      this adaptation has perceptual consequences beyond a shift in the perceived
      category boundary by measuring the effects of adaptation on RSVP, spatial search,
      and discrimination tasks. Adaptation had no discernable effect on performance for
      any of these tasks.

PMID- 18318605
TI  - Chromatic discrimination of natural objects.
AB  - Studies of chromatic discrimination are typically based on homogeneously colored
      patches. Surfaces of natural objects, however, cannot be characterized by a
      single color. Instead, they have a chromatic texture, that is, a distribution of
      different chromaticities. Here we study chromatic discrimination for natural
      images and synthetic stimuli with a distribution of different chromaticities
      under various states of adaptation. Discrimination was measured at the adaptation
      point, where the mean chromaticity of the test stimuli was the same as the
      chromaticity of the adapting background, and away from the adaptation point. At
      the adaptation point, discrimination for natural objects resulted in threshold
      contours that were selectively elongated in a direction of color space matching
      the chromatic variation of the colors within the natural object. Similar effects
      occurred for synthetic stimuli. Away from the adaptation point, discrimination
      thresholds increased and threshold ellipses were elongated along the contrast
      axis connecting adapting color and test color. Away from the adaptation point, no
      significant differences between the different stimulus classes were found. The
      effect of the chromatic texture on discrimination seemed to be masked by the
      overall increase in discrimination thresholds. Our results show that
      discrimination of chromatic textures, either synthetic or natural, differs from
      that of simple uniform patches when the chromatic variation is centered at the
      adaptation point.

PMID- 18318606
TI  - The initial interactions underlying binocular rivalry require visual awareness.
AB  - Current theories of binocular vision suggest that the neural processes that
      resolve interocular conflict do not involve a single brain region but occur at
      multiple stages of visual processing. Here, using an adaptation paradigm, we
      explore the initial mechanisms involved in selecting a stimulus for perceptual
      dominance during binocular rivalry. When one or both eyes briefly viewed an
      adapting grating stimulus prior to the presentation of the adapting grating to
      one eye and an orthogonal, non-adapted grating to the other eye, participants
      more often reported perceptual dominance of the non-adapted grating. Crowding
      reduced awareness of the adapting grating. On trials in which subjects were
      unaware of the orientation of the adaptor grating, there was no effect of the
      adaptor on perceived dominance during rivalry; participants were just as likely
      to report dominance of the adapted or non-adapted grating. This implies that the
      initial events in binocular rivalry involve later stages of visual processing.

PMID- 18318607
TI  - Localized information is necessary for scene categorization, including the
      Natural/Man-made distinction.
AB  - What information do people use to categorize scenes? Computational scene
      classification models have proposed that unlocalized amplitude information, the
      distribution of spatial frequencies and orientations, is useful for categorizing
      scenes. Previous research has provided conflicting results regarding this claim.
      Our previous research (Loschky et al., 2007) has shown that randomly localizing
      amplitude information (i.e., randomizing phase) greatly disrupts scene
      categorization at the basic level. Conversely, studies suggesting the usefulness
      of unlocalized amplitude information have used binary distinctions, e.g.,
      Natural/Man-made. We hypothesized that unlocalized amplitude information
      contributes more to the Natural/Man-made distinction than basic level
      distinctions. Using an established set of images and categories, we varied phase
      randomization and measured participants' ability to distinguish Natural versus
      Man-made scenes or scenes at the basic level. Results showed that eliminating
      localized information by phase randomization disrupted scene classification even
      for the Natural/Man-made distinction, demonstrating that amplitude localization
      is necessary for scene categorization.

PMID- 18318608
TI  - Perceptual learning of bisection stimuli under roving: slow and largely specific.
AB  - In perceptual learning, performance often improves within a short time if only
      one stimulus variant is presented, such as a line bisection stimulus with one
      outer-line-distance. However, performance stagnates if two bisection stimuli with
      two outer-line-distances are presented randomly interleaved. Recently, S. G.
      Kuai, J. Y. Zhang, S. A. Klein, D. M. Levi, and C. Yu, (2005) proposed that
      learning under roving conditions is impossible in general. Contrary to this
      proposition, we show here that perceptual learning with bisection stimuli under
      roving is possible with extensive training of 18000 trials. Despite this
      extensive training, the improvement of performance is still largely specific.
      Furthermore, this improvement of performance cannot be explained by an
      accommodation to stimulus uncertainty caused by roving.

PMID- 18318609
TI  - The correlation dimension: a useful objective measure of the transient visual
      evoked potential?
AB  - Visual evoked potentials (VEPs) may be analyzed by examination of the morphology
      of their components, such as negative (N) and positive (P) peaks. However,
      methods that rely on component identification may be unreliable when dealing with
      responses of complex and variable morphology; therefore, objective methods are
      also useful. One potentially useful measure of the VEP is the correlation
      dimension. Its relevance to the visual system was investigated by examining its
      behavior when applied to the transient VEP in response to a range of chromatic
      contrasts (42%, two times psychophysical threshold, at psychophysical threshold)
      and to the visually unevoked response (zero contrast). Tests of nonlinearity
      (e.g., surrogate testing) were conducted. The correlation dimension was found to
      be negatively correlated with a stimulus property (chromatic contrast) and a
      known linear measure (the Fourier-derived VEP amplitude). It was also found to be
      related to visibility and perception of the stimulus such that the dimension
      reached a maximum for most of the participants at psychophysical threshold. The
      latter suggests that the correlation dimension may be useful as a diagnostic
      parameter to estimate psychophysical threshold and may find application in the
      objective screening and monitoring of congenital and acquired color vision
      deficiencies, with or without associated disease processes.

PMID- 18318610
TI  - Head and eye movements and the role of memory limitations in a visual search
      paradigm.
AB  - The image information guiding visual behavior is acquired and maintained in an
      interplay of gaze shifts and visual short-term memory (VSTM). If storage capacity
      of VSTM is exhausted, gaze shifts can be used to regain information not currently
      represented in memory. By varying the separation between relevant image regions,
      S. Inamdar and M. Pomplun (2003) demonstrated a trade-off between VSTM storage
      and gaze shifts, which were performed as pure eye movements, that is, without a
      head movement component. Here we extend this paradigm to larger gaze shifts
      involving both eye and head movements. We use a comparative visual search
      paradigm with two relevant image regions and region separation as independent
      variable. Image regions were defined by two cupboards displaying colored
      geometrical objects in roughly equal arrangements. Subjects were asked to find
      differences in the arrangement of the objects in the two cupboards. Cupboard
      separation was varied between 30 degrees and 120 degrees . Images were presented
      with two projectors on a 150 degrees x 70 degrees curved screen. Head and eye
      movements were simultaneously recorded with an ART head tracker and an ASL mobile
      eye tracker, respectively. In the large separation conditions, the number of gaze
      shifts between the two cupboards was reduced, while fixation duration increased.
      Furthermore, the head movement proportions negatively correlated with the number
      of gaze shifts and positively correlated with fixation duration. We conclude that
      the visual system uses increased VSTM involvement to avoid gaze movements and in
      particular movements of the head. Scan path analysis revealed two subject
      specific strategies (encode left, compare right, and vice versa), which were
      consistently used in all separation conditions.

PMID- 18318611
TI  - Separating color from color contrast.
AB  - Visual objects can be described by their color and by their color contrast. For
      example, a red disk in front of a white background appears "red with high color
      contrast," whereas a red disk in front of a slightly less-saturated red
      background will appear "red with low color contrast." This paper examines the
      visual response to color contrast in a cone-based color space. The stimulus
      consists of two disks whose chromaticity and/or luminance modulate in time along
      a line in a DKL color space; the chromaticity and luminance levels of the two
      disks are always identical. One disk is surrounded by a static ring whose color
      is at one end of the color line, and the other disk is surrounded by a static
      ring whose color is at the opposite end of the color line. The disks appear to
      modulate in antiphase (following the contrast information), yet they can also
      appear to be approximately the same color (following the chromatic/luminance
      information). The observers' task was to adjust the color angle of modulating
      disks until the antiphase appearance was eliminated-creating a contrast null.
      Observers set contrast nulls at a color angle approximately 90 deg away from the
      line connecting the colors of the surround rings; this result occurred in both
      chromoluminant and equiluminant color planes, although two observers showed a
      flattening near equiluminance in the chromoluminance planes. To account for the
      data, I present a model that contains one pathway for color and another pathway
      for color contrast. I show that (1) the model correctly predicts orthogonal
      directions in color space for the contrast nulling task; (2) the response of the
      contrast pathway appears to be faster than the response of the color pathway; (3)
      the response of the contrast pathway may mediate detection thresholds under some
      conditions (a finding that can account for some of the effects of surround
      luminance on temporal sensitivity); (4) the asynchronous modulation can be seen
      even when the stimulus is blurred; and (5) the asynchrony does not require a disk
      ring configuration.

PMID- 18318612
TI  - More efficient scanning for familiar faces.
AB  - The present study reveals changes in eye movement patterns as newly learned faces
      become more familiar. Observers received multiple exposures to newly learned
      faces over four consecutive days. Recall tasks were performed on all 4 days, and
      a recognition task was performed on the fourth day. Eye movement behavior was
      compared across facial exposure and task type. Overall, the eyes were viewed for
      longer and more often than any other facial region, regardless of face
      familiarity. As a face became more familiar, observers made fewer fixations
      during recall and recognition. With increased exposure, observers sampled more
      from the eyes and sampled less from the nose, mouth, forehead, chin, and cheek
      regions. Interestingly, this change in scanning behavior was only observed for
      recall tasks, but not for recognition.

PMID- 18318613
TI  - The loss of the PDE6 deactivating enzyme, RGS9, results in precocious light
      adaptation at low light levels.
AB  - The GTPase activating protein, RGS9-1, is vital for the deactivation and
      regulation of the phototransduction cascade (C. K. Chen et al., 2000; C. W.
      Cowan, R. N. Fariss, I. Sokal, K. Palczewski, & T. G. Wensel, 1998; W. He, C. W.
      Cowan, & T. G. Wensel, 1998; A. L. Lyubarsky et al., 2001). Its loss through
      genetic defects in humans has been linked to a slow recovery to changes in
      illumination (K. M. Nishiguchi et al., 2004). Such a deficit is to be expected
      because RGS9-1 normally speeds up the deactivation of the activated
      phosphodiesterase effector molecule, PDE6*, and thus accelerates the turning off
      of the visual response. Paradoxically, however, we find that the cone response in
      an observer lacking RGS9-1 is faster at lower light levels than it is in a normal
      observer. Though surprising, this result is nonetheless consistent with molecular
      models of light adaptation (e.g., E. N. Pugh, S. Nikonov, & T. D. Lamb, 1999),
      which predict that the excess of PDE6* resulting from the loss of RGS9-1 will
      shorten the visual integration time and speed up the visual response at
      inappropriately low light levels. The gain in speed caused by the superfluity of
      PDE6* at lower light levels compensates for the loss caused by its slow
      deactivation; thus quickening the response relative to that in the normal. As the
      light level is increased and the PDE6* concentration in the normal rises relative
      to that in the observer lacking RGS9-1, the temporal advantage of the latter is
      soon lost, leaving only the deficit due to delayed deactivation.

PMID- 18318614
TI  - Geometric structure and chunking in reproduction of motion sequences.
AB  - Learning by imitation is fundamental to human behavior, but not all observed
      actions are equally easy to imitate. To understand why some actions are more
      difficult to imitate than others, we examined how higher-order relationships
      among the components of a stimulus model influenced the fidelity with which an
      action could be observed and then reproduced. With static contours, perception
      and short-term memory are strongly influenced by contour geometry, particularly
      by the presence and distribution of curvature extrema. To determine whether
      analogous relationships among subcomponents of a seen action would be important
      in encoding the action for subsequent reproduction, we manipulated actions'
      spatio-temporal geometry. In three experiments, we measured imitation fidelity
      for sequences of randomly directed, linked motions of a disc. The geometry of the
      disc's motion path strongly affected the accuracy of subsequent imitation: When
      the disc moved along a trajectory whose components were fairly consistent in
      their directions, imitation was strikingly better than when with irregular,
      jagged trajectories. A second experiment showed that this effect depended not
      upon co-variation in stimulus models' spatial extent, but rather on the
      relationship between successive movement directions. In a final, learning
      experiment, subjects had multiple opportunities to view and reproduce each model.
      The effect of the model's geometry persisted throughout the learning process,
      suggesting that it does not depend upon variables such as familiarity or
      expectancy but is somehow inherent to the pattern generated by the disc's motion.
      Our findings suggest that when analyzing seen actions, the brain privileges
      regular, consistent curvatures, grouping components that form a coherent shape
      into a unified "chunk." Inconsistencies among the directional components of a
      motion sequence cause the sequence to be chunked into additional components,
      which increases the load on working memory, undermining the fidelity with which
      the sequence can be imitated.

PMID- 18318615
TI  - The spatiotemporal profile of cortical processing leading up to visual
      perception.
AB  - Much controversy exists around the locus of conscious visual perception in human
      cortex. Some authors have proposed that its neural correlates correspond with
      recurrent processing within visual cortex, whereas others have argued they are
      located in a frontoparietal network. The present experiment aims to bring
      together these competing viewpoints. We recorded EEG from human subjects that
      were engaged in detecting masked visual targets. From this, we obtained a
      spatiotemporal profile of neural activity selectively related to the processing
      of the targets, which we correlated with the subjects' ability to detect those
      targets. This made it possible to distinguish between those stages of visual
      processing that correlate with human perception and those that do not. The
      results show that target induced extra-striate feedforward activity peaking at
      121 ms does not correlate with perception, whereas more posterior recurrent
      activity peaking at 160 ms does. Several subsequent stages show an alternating
      pattern of frontoparietal and occipital activity, all of which correlate highly
      with perception. This shows that perception emerges early on, but only after an
      initial feedforward volley, and suggests that multiple reentrant loops are
      involved in propagating this signal to frontoparietal areas.

PMID- 18318616
TI  - Illusory displacement due to object substitution near the consciousness
      threshold.
AB  - A briefly presented target shape can be made invisible by the subsequent
      presentation of a mask that replaces the target. While varying the target-mask
      interval in order to investigate perception near the consciousness threshold, we
      discovered a novel visual illusion. At some intervals, the target is clearly
      visible, but its location is misperceived. By manipulating the mask's size and
      target's position, we demonstrate that the perceived target location is always
      displaced to the boundary of a virtual surface defined by the mask contours.
      Thus, mutual exclusion of surfaces appears as a cause of masking.

PMID- 18318617
TI  - Highlight disparity contributes to the authenticity and strength of perceived
      glossiness.
AB  - The disparity of highlights on specular reflecting surfaces usually differs from
      the disparity of the surface points. A. Kirschmann (1895) proposed that this fact
      may be used as a binocular cue for gloss perception. This was confirmed by A.
      Blake and H. Bulthoff (1990) who found that subjects judged the glossiness of
      convex ellipsoidal surfaces as most realistic if the disparity of the highlights
      was close to the physical correct one. Extending on this finding, we investigate
      more closely whether the effect of highlight disparity depends on the sharpness
      of the highlight and the relative amount of diffuse and specular reflection. We
      measured the effect of highlight disparity on both perceived strength and
      perceived authenticity of gloss. We used complex, three-dimensional curved
      surfaces that were stereoscopically presented on a CRT. The reflection
      characteristics were varied using the Phong lighting model. Highlights were
      presented either with or without highlight disparity. In a rating experiment,
      subjects were asked to judge the strength and the authenticity of the perceived
      surface glossiness. The presence of highlight disparity lead to an enhancement of
      both the authenticity and the strength of perceived glossiness. The latter
      finding was confirmed in an additional matching experiment.

PMID- 18318618
TI  - Influence of adaptation state and stimulus luminance on peri-saccadic
      localization.
AB  - Spatial localization of flashed stimuli across saccades shows transient
      distortions of perceived position: Stimuli appear shifted in saccade direction
      and compressed towards the saccade target. The strength and spatial pattern of
      this mislocalization is influenced by contrast, duration, and spatial and
      temporal arrangement of stimuli and background. Because mislocalization of
      stimuli on a background depends on contrast, we asked whether mislocalization of
      stimuli in darkness depends on luminance. Since dark adaptation changes luminance
      thresholds, we compared mislocalization in dark-adapted and light-adapted states.
      Peri-saccadic mislocalization was measured with near-threshold stimuli and above
      threshold stimuli in dark-adapted and light-adapted subjects. In both adaptation
      states, near-threshold stimuli gave much larger mislocalization than above
      threshold stimuli. Furthermore, when the stimulus was presented near-threshold,
      the perceived positions of the stimuli clustered closer together. Stimulus
      luminance that produced strong mislocalization in the light-adapted state
      produced very little mislocalization in the dark-adapted state because it was now
      well above threshold. We conclude that the strength of peri-saccadic
      mislocalization depends on the strength of the stimulus: stimuli with near
      threshold luminance, and hence low visibility, are more mis-localized than
      clearly visible stimuli with high luminance.

PMID- 18318619
TI  - Apparent contrast differs across the vertical meridian: visual and attentional
      factors.
AB  - It is known that visual performance is better on the horizontal than the vertical
      meridian, and in the lower than the upper region of the vertical meridian
      (Vertical Meridian Asymmetry, "VMA"), and that exogenous spatial attention
      increases the apparent contrast of a stimulus. Here we investigate whether the
      VMA also leads to differences in the subjective appearance of contrast between
      the upper and lower vertical meridian, and how the effects of exogenous spatial
      attention on appearance interact with the VMA. Two Gabor stimuli were presented
      North and South of fixation at 4 degrees eccentricity along the vertical
      meridian. Observers were asked to report the orientation of the Gabor that was
      higher in contrast. By assessing which stimulus observers perceived to be higher
      in contrast, we obtained psychometric functions and their concomitant points of
      subjective equality (PSE). These functions were measured both when a neutral cue
      was presented in the middle of the display and transient attention was deployed
      via a peripheral cue to the location of one of the stimuli. Observers were told
      that the cues were uninformative as to the stimulus contrast or its orientation.
      We report two novel findings. First, apparent contrast is higher on the lower
      vertical meridian than on the upper. Second, the attentional enhancement of
      apparent contrast is asymmetrical with both low and high contrast stimuli; the
      effect of exogenous spatial attention is greater on the lower than the upper
      vertical meridian. As in prior studies, we find no corresponding asymmetry in
      orientation discrimination. Signal detection-based models explain the
      asymmetrical appearance effects as a function of differential multiplicative gain
      factors for the North and South locations, and predict a similar but much smaller
      asymmetry for orientation discrimination.

PMID- 18318620
TI  - Monitoring mouse retinal degeneration with high-resolution spectral-domain
      optical coherence tomography.
AB  - Progression of retinal degeneration in a mouse model was studied in vivo with
      high-resolution spectral-domain optical coherence tomography (SD-OCT). Imaging in
      3D with high depth resolution (<3 mum), SD-OCT resolved all the major layers of
      the retina of control C57BL/6J mice. Images of transgenic mice having a null
      mutation of the rhodopsin gene revealed the anatomical consequences of retinal
      degeneration: thinning of the outer retina, including the outer plexiform layer
      (OPL), outer nuclear layer (ONL), and inner and outer segments (IS/OS). We
      monitored the progression of retinal degeneration in rd1 mice (C3H/HeJ) by
      periodically imaging the same mice from the time the pups opened their eyes on
      P13 to P34. SD-OCT images showed that the outer retina (OPL, ONL, IS/OS) had
      already thinned by 73% (100 to 27 mum) at eye opening. The retina continued to
      degenerate, and by P20 the outer retina was not resolvable. The thickness of
      entire retina decreased from 228 mum (control) to 152 mum on P13 and to 98 mum by
      P34, a 57% reduction with the complete loss in the outer retina. In summary, we
      show that SD-OCT can monitor the progression of retinal degeneration in
      transgenic mice.

PMID- 18318621
TI  - Changes in crystalline lens radii of curvature and lens tilt and decentration
      during dynamic accommodation in rhesus monkeys.
AB  - Dynamic changes in crystalline lens radii of curvature and lens tilt and
      decentration were measured during centrally stimulated accommodation in four
      iridectomized eyes of two adolescent rhesus monkeys. Phakometry measurements were
      performed dynamically using a custom-built, video-based, Purkinje-image
      instrument. Lens anterior and posterior radii were calculated from reflections of
      paired light sources from the ocular surfaces (Purkinje images PI, PIII, and
      PIV). Lens tilt and decentration were calculated assuming linearity between
      Purkinje image positions, eye rotation, lens tilt, and decentration. Because the
      monkey eyes were iridectomized, Purkinje images were referred to the mid-point of
      the double first Purkinje image (PI). Mean unaccommodated values of anterior and
      posterior lens radii of curvature were 11.11 +/- 1.58 mm and -6.64 +/- 0.62 mm,
      respectively, and these decreased relatively linearly with accommodation in all
      eyes, at a rate of 0.48 +/- 0.14 mm/D and 0.17 +/- 0.03 mm/D for anterior and
      posterior lens surfaces, respectively. Tilt and decentration did not change
      significantly with accommodation except for tilt around the horizontal axis,
      which changed at a rate of 0.147 +/- 0.25 deg/D. These results are important to
      fully characterize accommodation in rhesus monkeys.

PMID- 18318622
TI  - On the decline of 1st and 2nd order sensitivity with eccentricity.
AB  - We studied the relationship between the decline in sensitivity that occurs with
      eccentricity for stimuli of different spatial scale defined by either luminance
      (LM) or contrast (CM) modulation. We show that the detectability of CM stimuli
      declines with eccentricity in a spatial frequency-dependent manner, and that the
      rate of sensitivity decline for CM stimuli is roughly that expected from their
      1st order carriers, except, possibly, at finer scales. Using an equivalent noise
      paradigm, we investigated the possible reasons for why the foveal sensitivity for
      detecting LM and CM stimuli differs as well as the reason why the detectability
      of 1st order stimuli declines with eccentricity. We show the former can be
      modeled by an increase in internal noise whereas the latter involves both an
      increase in internal noise and a loss of efficiency. To encompass both the
      threshold and suprathreshold transfer properties of peripheral vision, we propose
      a model in terms of the contrast gain of the underlying mechanisms.

PMID- 18318623
TI  - Covert inhibition potentiates online control in a double-step task.
AB  - A planned action awaiting execution requires withholding a prepared response. We
      asked whether such a form of inhibition would interact with online decision
      processes that require changes in planned responses when new goals are
      unexpectedly specified. To investigate this issue with respect to oculomotor
      control, subjects performed, in separate sessions, standard visually-guided (SV)
      saccades, or memory-guided (MG) and delayed visually-guided (DV) saccades, both
      of which required withholding a planned saccade. To probe control, a second
      target (target-step) was presented in some trials after a variable delay that
      instructed subjects to redirect their gaze to the newly specified target. The
      time taken to cancel or inhibit the saccade directed at the initial target, the
      target step reaction time, was calculated using a race model that hypothesizes a
      covert inhibitory process, and was found to be significantly smaller for memory
      guided redirect task (MGR; 94 ms) and delayed visually-guided redirect task (DVR;
      96 ms) compared to standard visually-guided redirect task (SVR; 117 ms),
      suggesting facilitation of online inhibition in MGR and DVR. These results
      suggest that a tonic level of inhibition interacts with online decision processes
      to potentiate inhibitory control during double-step tasks.

PMID- 18318624
TI  - Visual-haptic cue weighting is independent of modality-specific attention.
AB  - Some object properties (e.g., size, shape, and depth information) are perceived
      through multiple sensory modalities. Such redundant sensory information is
      integrated into a unified percept. The integrated estimate is a weighted average
      of the sensory estimates, where higher weight is attributed to the more reliable
      sensory signal. Here we examine whether modality-specific attention can affect
      multisensory integration. Selectively reducing attention in one sensory channel
      can reduce the relative reliability of the estimate derived from this channel and
      might thus alter the weighting of the sensory estimates. In the present study,
      observers performed unimodal (visual and haptic) and bimodal (visual-haptic) size
      discrimination tasks. They either performed the primary task alone or they
      performed a secondary task simultaneously (dual task). The secondary task
      consisted of a same/different judgment of rapidly presented visual letter
      sequences, and so might be expected to withdraw attention predominantly from the
      visual rather than the haptic channel. Comparing size discrimination performance
      in single- and dual-task conditions, we found that vision-based estimates were
      more affected by the secondary task than the haptics-based estimates, indicating
      that indeed attention to vision was more reduced than attention to haptics. This
      attentional manipulation, however, did not affect the cue weighting in the
      bimodal task. Bimodal discrimination performance was better than unimodal
      performance in both single- and dual-task conditions, indicating that observers
      still integrate visual and haptic size information in the dual-task condition,
      when attention is withdrawn from vision. These findings indicate that visual
      haptic cue weighting is independent of modality-specific attention.

PMID- 18318625
TI  - Temporal dynamics of directional selectivity in human vision.
AB  - We used psychophysical reverse correlation to determine how directional signals
      are integrated across a time window of 300 ms. Directional tuning was time
      independent within the resolution of our measurements, as demonstrated by the
      fact that the perceptual filter was almost perfectly separable in its temporal
      and directional dimensions. The amplitude of the filter peaked very early (30-60
      ms) and then quickly decreased to almost zero, after which it increased slightly
      again. We successfully modeled this bimodal behavior using a simple circuit where
      each directional filter normalizes its own output, with the normalizing signal
      delayed by approximately 100 ms.

PMID- 18318626
TI  - A scale invariant measure of clutter.
AB  - We propose a measure of clutter for real images that can be used to predict
      search times. This measure uses an efficient segmentation algorithm (P.
      Felzenszwalb & D. Huttenlocher, 2004) to count the number of regions in an image.
      This number is not uniquely defined, however, because it varies with the scale of
      segmentation. The relationship between the number of regions and the scale of
      segmentation follows a power law, and the exponent of the power law is similar
      across images. We fit power law functions to the multiple scale segmentations of
      160 images. The power law exponent was set to the average value for the set of
      images, and the constant of proportionality was used as a measure of image
      clutter. The same 160 images were also used as stimuli in a visual search
      experiment. This scale-invariant measure of clutter accounted for about 40% of
      the variance in the visual search times.

PMID- 18318627
TI  - Anti-Glass patterns and real motion perception: same or different mechanisms?
AB  - A sequence of anti-Glass patterns, composed by dot pairs with opposite luminance
      polarity, elicits a clear perception of motion in the direction of the white dot
      of the pair. This effect can be reversed by introducing a delay in the
      presentation of white dots, suggesting a faster processing of light dots as a
      cause of the motion signal (M. M. Del Viva, M. Gori, & D. C. Burr, 2006). If this
      hypothesis is correct, anti-Glass patterns should interact with real motion
      signals. In this study, we compare the motion induced by these stimuli to test
      whether they are analyzed by the same motion mechanism. We found that motion
      induced by anti-Glass patterns annuls real motion, when they are presented
      simultaneously in the same display and moving in opposite directions. By lowering
      the contrast of one of them, motion toward the stimulus with higher contrast
      prevails. We also found sub-threshold summation of motion induced by anti-Glass
      patterns and real motion, when presented simultaneously and moving in the same
      direction. These findings indicate that anti-Glass patterns and moving stimuli
      are processed by the same, contrast-dependent motion mechanism and lend further
      support to the proposed explanation of the effect.

PMID- 18318628
TI  - Task-demands can immediately reverse the effects of sensory-driven saliency in
      complex visual stimuli.
AB  - In natural vision both stimulus features and task-demands affect an observer's
      attention. However, the relationship between sensory-driven ("bottom-up") and
      task-dependent ("top-down") factors remains controversial: Can task-demands
      counteract strong sensory signals fully, quickly, and irrespective of bottom-up
      features? To measure attention under naturalistic conditions, we recorded eye
      movements in human observers, while they viewed photographs of outdoor scenes. In
      the first experiment, smooth modulations of contrast biased the stimuli's sensory
      driven saliency towards one side. In free-viewing, observers' eye-positions were
      immediately biased toward the high-contrast, i.e., high-saliency, side. However,
      this sensory-driven bias disappeared entirely when observers searched for a
      bull's-eye target embedded with equal probability to either side of the stimulus.
      When the target always occurred in the low-contrast side, observers' eye
      positions were immediately biased towards this low-saliency side, i.e., the
      sensory-driven bias reversed. Hence, task-demands do not only override sensory
      driven saliency but also actively countermand it. In a second experiment, a 5-Hz
      flicker replaced the contrast gradient. Whereas the bias was less persistent in
      free viewing, the overriding and reversal took longer to deploy. Hence,
      insufficient sensory-driven saliency cannot account for the bias reversal. In a
      third experiment, subjects searched for a spot of locally increased contrast
      ("oddity") instead of the bull's-eye ("template"). In contrast to the other
      conditions, a slight sensory-driven free-viewing bias prevails in this condition.
      In a fourth experiment, we demonstrate that at known locations template targets
      are detected faster than oddity targets, suggesting that the former induce a
      stronger top-down drive when used as search targets. Taken together, task-demands
      can override sensory-driven saliency in complex visual stimuli almost
      immediately, and the extent of overriding depends on the search target and the
      overridden feature, but not on the latter's free-viewing saliency.

PMID- 18318629
TI  - Learning optimal integration of arbitrary features in a perceptual discrimination
      task.
AB  - A number of studies have demonstrated that people often integrate information
      from multiple perceptual cues in a statistically optimal manner when judging
      properties of surfaces in a scene. For example, subjects typically weight the
      information based on each cue to a degree that is inversely proportional to the
      variance of the distribution of a scene property given a cue's value. We wanted
      to determine whether subjects similarly use information about the reliabilities
      of arbitrary low-level visual features when making image-based discriminations,
      as in visual texture discrimination. To investigate this question, we developed a
      modification of the classification image technique and conducted two experiments
      that explored subjects' discrimination strategies using this improved technique.
      We created a basis set consisting of 20 low-level features and created stimuli by
      linearly combining the basis vectors. Subjects were trained to discriminate
      between two prototype signals corrupted with Gaussian feature noise. When we
      analyzed subjects' classification images over time, we found that they modified
      their decision strategies in a manner consistent with optimal feature
      integration, giving greater weight to reliable features and less weight to
      unreliable features. We conclude that optimal integration is not a characteristic
      specific to conventional visual cues or to judgments involving three-dimensional
      scene properties. Rather, just as researchers have previously demonstrated that
      people are sensitive to the reliabilities of conventionally defined cues when
      judging the depth or slant of a surface, we demonstrate that they are likewise
      sensitive to the reliabilities of arbitrary low-level features when making image
      based discriminations.

PMID- 18318630
TI  - Occlusion and the solution to visual motion ambiguity: Looking beyond the
      aperture problem.
AB  - A horizontally moving grating viewed within a diamond-shaped aperture can be made
      to appear to move obliquely by introducing appropriate depth-ordering cues (R. O.
      Duncan, T. D. Albright, & G. R. Stoner, 2000). It is commonly assumed that the
      depth cues in such displays determine which line terminators are seen as
      intrinsic to the grating and which are seen as resulting from occlusion and hence
      extrinsic to the grating. The ambiguous motion of the grating (arising from the
      aperture problem) is then supposed to be overcome by selectively pooling motion
      signals arising from the intrinsic terminators with those arising from the
      grating while discounting the motion of the extrinsic terminators. In our first
      experiment, we tested the sufficiency of this explanation. Observers reported the
      direction of motion of ambiguously moving random dots viewed through a diamond
      shaped aperture defined by four panels. Binocular disparity was used to simulate
      occlusion: two panels occluded the virtual surface upon which the dots were
      positioned and two panels were occluded by that surface. Reports were
      significantly biased toward the direction of the occluding panels. Since none of
      the moving features abutted the surrounding panels, none should have been
      classified as extrinsic and hence this result cannot have relied on terminator
      classification. In a second experiment, we tested the hypothesis that depth
      ordering cues selectively gate the propagation of motion signals so that the
      representation of the moving surface extends behind the occluders. This was
      tested by asking observers to report the direction of moving dots viewed through
      a briefly "opened" probe window within either occluding or occluded panels.
      Consistent with our hypothesis, evidence of motion propagation was only found for
      probe windows within occluding panels. Surprisingly, however, this propagation
      was only observed when the dots in the inducer window moved away from the probe
      window, suggesting a "pull," and not a "push" mechanism.

PMID- 18318631
TI  - The L:M cone ratio in males of African descent with normal color vision.
AB  - Among Caucasian males with normal color vision, long-wavelength-sensitive (L)
      cones outnumber middle-wavelength-sensitive (M) cones by nearly three to one, on
      average, and the L and the M cone opsin genes are arrayed on the X-chromosome
      with the L opsin gene being closest to an upstream enhancer element termed the
      locus control region (LCR). Interaction between an opsin gene promoter and the
      LCR is required to mediate normal opsin gene expression, and the relative
      proximity of the L opsin gene promoter (4,000 base pairs for L compared to 40,000
      base pairs for the M opsin gene promoter) has been proposed to endow the L gene
      with the advantage in competing for interaction with the LCR, thereby accounting
      for the nearly 3:1 ratio of L:M cones. This proximal advantage hypothesis
      predicts that the L:M cone ratio will be similar among populations that share the
      same X-chromosome opsin gene array organization. Here, we tested this hypothesis
      by examining a sample of males of African descent and found them to have a
      significantly different average L:M ratio compared to Caucasian males, even
      though their X-chromosome opsin gene arrays were indistinguishable from arrays in
      males of Caucasian descent. How these observations might be reconciled is
      discussed.

PMID- 18318632
TI  - What can saliency models predict about eye movements? Spatial and sequential
      aspects of fixations during encoding and recognition.
AB  - Saliency map models account for a small but significant amount of the variance in
      where people fixate, but evaluating these models with natural stimuli has led to
      mixed results. In the present study, the eye movements of participants were
      recorded while they viewed color photographs of natural scenes in preparation for
      a memory test (encoding) and when recognizing them later. These eye movements
      were then compared to the predictions of a well defined saliency map model (L.
      Itti & C. Koch, 2000), in terms of both individual fixation locations and
      fixation sequences (scanpaths). The saliency model is a significantly better
      predictor of fixation location than random models that take into account bias
      toward central fixations, and this is the case at both encoding and recognition.
      However, similarity between scanpaths made at multiple viewings of the same
      stimulus suggests that repetitive scanpaths also contribute to where people look.
      Top-down recapitulation of scanpaths is a key prediction of scanpath theory (D.
      Noton & L. Stark, 1971), but it might also be explained by bottom-up guidance.
      The present data suggest that saliency cannot account for scanpaths and that
      incorporating these sequences could improve model predictions.

PMID- 18318633
TI  - If I saw it, it probably wasn't far from where I was looking.
AB  - People are most likely to see something if their gaze is directed at it. Thus if
      they saw something they may be biased towards believing that they had been
      looking at it. In order to examine whether this is so we asked participants where
      a target that jumped to a new position every 250 ms had been at a moment
      indicated by a flash or a tone. The jumping introduced uncertainty about where
      the target was at the indicated moment, giving room for biases to be expressed.
      Participants showed a clear preference to select positions that were nearer to
      where they were looking.

PMID- 18318634
TI  - Contrast and stimulus information effects in rapid learning of a visual task.
AB  - We have previously described a psychophysical paradigm for investigating rapid
      learning of relevant visual information in detection tasks (M. P. Eckstein, C. K.
      Abbey, B. T. Pham, & S. S. Shimozaki, 2004). This paradigm uses blocked trials
      with a set of possible target profiles, and it has demonstrated learning effects
      after a single trial. When targets are masked by Gaussian luminance noise, there
      exists a Bayesian ideal observer that also exhibits learning effects over the
      trials within a block. In this work, we investigate the effect of target contrast
      and the effect of the information to be learned in the target profile set.
      Absolute efficiency tracks target contrast closely and ranges from approximately
      10% to 25% in these experiments. To disambiguate learning from other effects
      contributing to absolute efficiency, we define a measure of learning efficiency
      that measures the observed improvement over a block of trials against the total
      improvement expected in the ideal observer. We find significant positive trends
      in learning efficiency both over contrast and the within-block trial number. We
      find that a two-feature profile set containing orientation and polarity
      differences leads to a greater within-block gain in performance than a one
      feature profile set that contains only orientation differences. However, this
      apparent difference disappears when efficiency is compared. Lastly, we show that
      the disparity between task performance and accumulated knowledge of the target
      profile can be largely explained by a model that only allows learning to occur in
      trials the observer performs correctly.

PMID- 18318635
TI  - Object features used by humans and monkeys to identify rotated shapes.
AB  - Humans and rhesus monkeys can identify shapes that have been rotated in the
      picture plane. Recognition of rotated shapes can be as efficient as recognition
      of upright shapes. Here we investigate whether subjects showing view-invariant
      performance use the same object features to identify upright and rotated versions
      of a shape. We find marked differences between humans and monkeys. While humans
      tend to use the same features independent of shape orientation, monkeys use
      unique features for each orientation. Humans are able to generalize to a greater
      degree across orientation changes than rhesus monkey observers, who tend to
      relearn separate problems at each orientation rather than flexibly apply
      previously learned knowledge to novel problems.

PMID- 18318636
TI  - Integration of ordinal and metric cues in depth processing.
AB  - J. Burge, M. A. Peterson, and S. E. Palmer (2005) reported that ordinal,
      configural cues of familiarity and convexity influence perceived depth even when
      unambiguous metric information in the form of binocular disparity is available.
      In their study, a shape that was both convex and familiar (i.e., a face)
      increased perceived depth in random dot stereograms if the shape was shown in the
      foreground and decreased perceived depth if it was shown in the background. It is
      generally assumed that luminance cues are necessary for pre-figural shape
      representation to influence figure-ground computations in this way (M. A.
      Peterson & B. S. Gibson, 1993); thus, Burge et al. (2005) had used a luminance
      edge. In this research, we asked whether configural cues need to be defined by
      luminance, contrast, or neither. For a sufficiently large disparity pedestal
      (about 2.5 arcmin), configural cues influenced perceived depth both for second
      order contours and for contours defined only by disparity. The integration of
      ordinal and metric cues seems to be driven by the general saliency of the
      contours and not only by luminance information. This challenges the notion that
      the integration of such cues always needs to arise during figure-ground
      organization through early combinations of luminance-defined shape and binocular
      disparity.

PMID- 18318637
TI  - Motion-induced blindness is not tuned to retinal speed.
AB  - Motion-induced blindness is a visual phenomenon in which a moving pattern can
      cause superimposed static targets that remain physically present to
      intermittently disappear from awareness. To date, there has been little
      systematic investigation of the type of motion that induces the most robust
      perceptual disappearances. To address this issue, we investigated the temporal
      frequency and stimulus speed sensitivity of this phenomenon in two experiments.
      In the first, we used radial gratings and waveform modulation to decouple
      spatiotemporal frequency and retinal speed characteristics. The results suggested
      that motion-induced disappearances are tuned to temporal frequency, but not to
      stimulus speed. In the second, we showed that luminance flicker-induced
      disappearances were tuned to the same temporal frequency as motion-induced
      disappearances. In combination, these data suggest that motion-induced blindness
      does not depend on retinal stimulus speed. Rather, it seems to be broadly tuned
      for moderate rates of temporal modulation. This observation is reminiscent of
      other instances where motion and spatial coding interact to modulate visibility.

PMID- 18318638
TI  - First- and second-order motion mechanisms are distinct at low but common at high
      temporal frequencies.
AB  - There is no consensus on the type of nonlinearity enabling motion processing of
      second-order stimuli. Some authors suggest that a nonlinearity specifically
      applied to second-order stimuli prior to motion processing (e.g., rectification
      process) recovers the spatial structure of the signal permitting subsequent first
      order motion analyses (e.g., filter-rectify-filter model). Others suggest that
      nonlinearities within motion processing enable first-order-sensitive mechanisms
      to process second-order stimuli (e.g., gradient-based model). In the present
      study, we evaluated intra- and inter-attribute interactions by measuring the
      impact of dynamic noise modulators (either luminance (LM) or contrast-modulated
      (CM)) on the processing of moving LM and CM gratings. When the signal and noise
      were both of the same type, similar calculation efficiencies but different
      internal equivalent noises were observed at all temporal frequencies. At high
      temporal frequencies, each noise type affected both attributes by similar
      proportions suggesting that both attributes are processed by common mechanisms.
      Conversely, at low temporal frequencies, each noise type primarily impaired the
      processing of the attribute of the same type suggesting distinct mechanisms. We
      therefore conclude that two fundamentally different mechanisms are processing CM
      stimuli: one low-pass and distinct from the mechanisms processing LM stimuli and
      the other common to the mechanisms processing LM stimuli.

PMID- 18318639
TI  - How keratoconus influences optical performance of the eye.
AB  - Using a statistical description of keratoconus (KC) topography, schematic eye
      models of various KC conditions are constructed to study their optical influence
      on visual performance. The cone shape, protruding height and extent, and distance
      from the visual zone are independently investigated with the three-dimensional
      optical eye-modeling and ray-tracing techniques. The subsequent spherical
      equivalent (SE), cylinder, together with residual high-order ocular aberrations,
      are examined and related to each separated variable. The results show that myopic
      nature of SE is greatly dominated by the location of the cone. The cylinder is
      determined by the cone shape when the cone is inside the visual zone. It is
      dominated by the cone location when the cone is away from visual axis. The least
      myopic meridian always falls on the cone direction, and the high-order
      aberrations strongly relate to the cone dimension. This study investigates KC
      cone effect on optical quality and provides comprehension of clinical
      observations.

PMID- 18318640
TI  - A single "stopwatch" for duration estimation, a single "ruler" for size.
AB  - Although observers can discriminate visual targets with long exposures from
      otherwise-identical targets with shorter exposures, temporally overlapping
      distracters with an intermediate exposure can produce a striking degradation in
      performance. This new finding suggests that observers can only estimate one
      duration at a time. Discrimination on the basis of size, rather than duration,
      did not degrade as rapidly with the number of distracters but was still worse
      than predicted by unlimited-capacity models. The critical difference between
      estimates of temporal length and estimates of spatial length seems to be that the
      former can only be made at the end of an exposure, while the latter can be made
      at any time during an exposure. When sizes varied throughout the trial and
      decisions were based on terminal sizes, the set-size effect was as large as that
      obtained for duration discrimination. We conclude that when textural filters are
      not available for segregating a target from distracters, efficient estimates of
      size or duration require the serial examination of individual display items.

PMID- 18318641
TI  - Nearly instantaneous brightness induction.
AB  - Brightness induction is the modulation of the perceived intensity of a region by
      the luminance of surrounding regions and reveals fundamental properties of neural
      organization in the visual system. Grating induction affords a unique opportunity
      to precisely measure the temporal properties of induction using a quadrature
      motion technique. Contrary to previous reports that induction is a sluggish
      process with temporal frequency cutoffs of 2-5 Hz (R. L. DeValois, M. A. Webster,
      K. K. DeValois, & B. Lingelbach, 1986; A. F. Rossi & M. A. Paradiso, 1996), we
      find that induction is nearly instantaneous. The temporal response of induced
      brightness differs from that of luminance gratings by a small time lag (<1 ms),
      or by a small temporal phase lag (<0.016 cycle), and remains relatively constant
      across wide variations in test field height. These data are not easily explained
      by an edge-dependent, homogeneous filling-in process (A. F. Rossi & M. A.
      Paradiso, 1996); however, they are consistent with an explanation of brightness
      induction based on spatial filtering by cortical simple cells (B. Blakeslee & M.
      E. McCourt, 1999).

PMID- 18318642
TI  - Gating of remote effects on lightness.
AB  - In various versions of the dungeon illusion (P. Bressan, 2001), we show that
      grouping between targets and contextual disks determines whether remote
      luminances affect target lightness or not. In the dungeon illusion, target disks
      surrounded by contextual disks contrast with them rather than with the immediate
      background. We formally establish the existence of this illusion and show that it
      reverses when the luminance of the targets is either lower (double decrement) or
      higher (double increment) than the luminances of both the background and the
      contextual disks rather than in between them. On the basis of the double
      anchoring theory of lightness (P. Bressan, 2006a), we predict and show that
      grouping gates the effects of remote luminances in such a way that they go in
      opposite directions in the double-decrement and double-increment inverted-dungeon
      illusions. Our results support the double-anchoring theory and demonstrate that
      luminances that are far away from the targets are irrelevant in some conditions
      but critical in others.

PMID- 18318644
TI  - Bone-targeted replacement therapy for hypophosphatasia.

PMID- 18318645
TI  - Winning the battle against childhood physical inactivity: the key to bone
      strength?

PMID- 18318643
TI  - Considerations for development of surrogate endpoints for antifracture efficacy
      of new treatments in osteoporosis: a perspective.
AB  - Because of the broad availability of efficacious osteoporosis therapies, conduct
      of placebo-controlled trials in subjects at high risk for fracture is becoming
      increasing difficult. Alternative trial designs include placebo-controlled trials
      in patients at low risk for fracture or active comparator studies, both of which
      would require enormous sample sizes and associated financial resources. Another
      more attractive alternative is to develop and validate surrogate endpoints for
      fracture. In this perspective, we review the concept of surrogate endpoints as it
      has been developed in other fields of medicine and discuss how it could be
      applied in clinical trials of osteoporosis. We outline a stepwise approach and
      possible study designs to qualify a biomarker as a surrogate endpoint in
      osteoporosis and review the existing data for several potential surrogate
      endpoints to assess their success in meeting the proposed criteria. Finally, we
      suggest a research agenda needed to advance the development of biomarkers as
      surrogate endpoints for fracture in osteoporosis trials. To ensure optimal
      development and best use of biomarkers to accelerate drug development, continuous
      dialog among the health professionals, industry, and regulators is of paramount
      importance.

PMID- 18318646
TI  - Different intrafamilial clinical presentation of FMF mutation carriers.
AB  - Familial Mediterranean fever (FMF) is a heterogeneous disorder; at present, it is
      diagnosed using only genetic methods. In the current study, we performed
      molecular analysis in two families presenting with FMF. In the first family, we
      report two brothers with a common genotype (M694V/V726A) but with different
      clinical presentation. In the second family, we identified the M694V and K695R
      mutations in a presymptomatic carrier.

PMID- 18318647
TI  - Associations between anticipated reactions to genetic test results and interest
      in genetic testing: will self-selection reduce the potential for harm?
AB  - The proliferation of genetic susceptibility tests for complex diseases away from
      clinic settings increases the potential for harm. This study assessed whether
      people are likely to self-select themselves into or out of genetic testing
      depending on whether they believe they could cope with the results. Associations
      between anticipated reactions to adverse genetic test results and interest in
      taking genetic tests for cancer and heart disease were examined in a community
      sample of English adults (n = 1,024). Interest in genetic testing overall was 78%
      for cancer risk and 80% for heart disease risk. As predicted, there were
      differences by anticipated reactions. People who anticipated regret about having
      taken a genetic test for cancer risk expressed lower interest than those who did
      not anticipate regret (46% vs. 89%), and people who anticipated being glad to
      know of increased risk status (i.e., reduced uncertainty) were more interested
      than those who did not look forward to reduced uncertainty (91% vs. 22%).
      Patterns were similar for heart disease ("regret" 66% vs. 87%; "reduced
      uncertainty" 87% vs. 38%). The potential for harm from future genetic
      susceptibility tests may be less than feared if people who anticipate adverse
      reactions self-select themselves out of testing. However, given that a
      significant proportion of people who anticipated adverse reactions also expressed
      interest in testing, there is still a concern about safety. It remains to be seen
      whether the same patterns emerge in studies that actually offer genetic tests for
      common gene variants in community settings.

PMID- 18318648
TI  - Rising atmospheric carbon dioxide and plant biology: the overlooked paradigm.

PMID- 18318649
TI  - Emerging application of quantum dots for drug delivery and therapy.
AB  - Quantum dots have proven themselves as powerful fluorescent probes, especially
      for long-term, multiplexed, and quantitative imaging and detection. Newly
      engineered quantum dots with integrated targeting, imaging and therapeutic
      functionalities have become excellent material to study drug delivery in cells
      and small animals. This fluorescent 'prototype' will provide important
      information in the rational design of biocompatible drug carriers and will serve
      as a superior alternative to magnetic and radioactive imaging contrast agents in
      preclinical drug screening, validation and delivery research. This Editorial
      article is not intended to offer a comprehensive review on drug delivery, but to
      highlight the breakthroughs in the emerging applications of quantum dots in this
      field and to provide our perspective on future research.

PMID- 18318650
TI  - Disease guided optimization of the respiratory delivery of microparticulate
      formulations.
AB  - BACKGROUND: Inhalation of microparticulate dosage forms can be effectively used
      in the treatment of respiratory and systemic diseases. OBJECTIVE: Disease states
      investigated for treatment by inhalation of microparticles were reviewed along
      with the drugs' pharmacological, pharmacokinetic and physical chemical properties
      to identify the advantages of microparticulate inhalation formulations and to
      identify areas for further improvement. METHODS: Microbial infections of the
      lung, asthma, diabetes, lung transplantation and lung cancer were examined, with
      a focus on those systems intended to provide a sustained release. CONCLUSION: In
      developing microparticulate formulations for inhalation in the lung, there is a
      need to understand the pharmacology of the drug as the key to revealing the
      optimal concentration time profile, the disease state, and the pharmacokinetic
      properties of the pure drug as determined by IV administration and inhalation.
      Finally, in vitro release studies will allow better identification of the best
      dosing strategy to be used in efficacy and safety studies.

PMID- 18318651
TI  - Lipid implants as drug delivery systems.
AB  - The parenteral controlled delivery of acid-labile drugs (e.g., proteins) is
      difficult, because the standard polymer poly(lactic-co-glycolic acid) used to
      control drug release upon parenteral administration degrades into shorter chain
      acids, creating acidic microclimates. Lipid implants do not show this
      disadvantage. The objective of this article is to give an overview on the present
      state of the art and to highlight the advantages and drawbacks of the different
      types of systems reported in the literature. The major preparation techniques for
      lipid implants, underlying mass transport mechanisms, biocompatibility and in
      vivo performance of the most interesting systems are described. Lipid implants
      offer a great potential as parenteral controlled drug delivery systems,
      especially for protein-based drugs. A broad spectra of release patterns can be
      provided and acidic microclimates avoided.

PMID- 18318652
TI  - Targeted drug delivery via folate receptors.
AB  - Targeted delivery via selective cellular markers can potentially increase the
      efficacy and reduce the toxicity of therapeutic agents. The folate receptor (FR)
      has two glycosyl phosphatidylinositol (GPI)-anchored isoforms, alpha and beta. FR
      alpha expression is frequently amplified in epithelial cancers, whereas FR-beta
      expression is found in myeloid leukemia and activated macrophages associated with
      chronic inflammatory diseases. Conjugates of folic acid and anti-FR antibodies
      can be taken up by cancer cells via receptor-mediated endocytosis, thus providing
      a mechanism for targeted delivery to FR+ cells. The aim of this article is to
      provide a brief overview of applications of FR targeting in drug delivery, with
      an emphasis on the strategy of using folate as a targeting ligand. In order to do
      this, recent literature is surveyed on targeted delivery via both FR sub-types,
      as well as new findings on selective receptor upregulation in the targeted cells.
      A wide variety of molecules and drug carriers, including imaging agents,
      chemotherapeutic agents, oligonucleotides, proteins, haptens, liposomes,
      nanoparticles and gene transfer vectors have been conjugated to folate and
      evaluated for FR-targeted delivery. Substantial targeting efficacy has been found
      both in vitro and in vivo. In addition, mechanisms and methods for selective FR
      upregulation have been uncovered, which might enhance the effectiveness of the FR
      targeted delivery strategy. FR-alpha serves as a useful marker for cancer,
      whereas FR-beta serves as a marker for myeloid leukemia and chronic inflammatory
      diseases. FR-targeted agents have shown promising efficacy in preclinical models
      and significant potential for future clinical application in a wide range of
      diseases.

PMID- 18318653
TI  - Targeted filamentous bacteriophages as therapeutic agents.
AB  - Bacteriophages (phages) have been used for therapy of bacterial infections, for
      genetic research, as tools for the discovery of specific target binding proteins
      and for vaccine development. The aim of this article is to present advances in
      genetic and chemical engineering of filamentous bacteriophages that facilitated
      their application for therapeutic purposes. We review studies where phages were
      applied for in vivo imaging, as gene delivery vehicles and as drug carriers.
      Target specificity is based on peptides or proteins displayed on the phage coat.
      The cargo may be a packaged gene incorporated into the phage genome for gene
      delivery applications, or imaging agents or cytotoxic drugs chemically conjugated
      at high density onto the phage coat. We believe that the combination of those
      separately developed methodologies would result in clinical applications of phage
      based therapeutics.

PMID- 18318654
TI  - Opportunities and challenges of carbon-based nanomaterials for cancer therapy.
AB  - The possibility of incorporating carbon-based nanomaterials into living systems
      has opened the way for the investigation of their potential applications in the
      emerging field of nanomedicine. A wide variety of different nanomaterials based
      on allotropic forms of carbon, such as nanotubes, nanohorns and nanodiamonds, are
      currently being explored towards different biomedical applications. In this
      review, we discuss the recent advances in the development of these novel
      nanomaterials for cancer therapy. A comparison between the characteristics, the
      advantages, the drawbacks, the benefits and the risks associated with these novel
      biocompatible forms of carbon is presented here.

PMID- 18318655
TI  - Nanodisks: hydrophobic drug delivery vehicles.
AB  - Members of the class of exchangeable apolipoproteins possess the unique capacity
      to transform phospholipid vesicle substrates into nanoscale disk-shaped bilayers.
      This reaction can proceed in the presence of exogenous hydrophobic biomolecules,
      resulting in the formation of novel transport vehicles termed nanodisks (NDs).
      The objective of this study is to describe the structural organization of NDs and
      evaluate the utility of these complexes as hydrophobic biomolecule transport
      vehicles. The topics presented focus on two distinct water insoluble drugs,
      amphotericin B (AMB) and all trans retinoic acid (ATRA). In vitro and in vivo
      studies reveal that AMB-ND display potent anti-fungal and anti-protozoal
      activity, while ATRA-ND show promise in the treatment of cancer. The versatility
      conferred by the presence of a polypeptide component provides opportunities for
      targeted delivery of ND to cells.

PMID- 18318656
TI  - Thermally targeted delivery of chemotherapeutics and anti-cancer peptides by
      elastin-like polypeptide.
AB  - Current chemotherapy treatment of solid tumors is limited due to a lack of
      specific delivery of the drugs to the tumor, leading to systemic toxicity.
      Therefore, it is necessary to develop targeted cancer therapies and tumor
      targeted drug carriers. The authors review the development of elastin-like
      polypeptide (ELP) as a potential carrier for thermally targeted delivery of
      therapeutics. The authors searched Medline for articles concerning the
      application of ELP as a drug delivery vector for small molecule drugs and
      therapeutic peptides. ELP has been demonstrated to be a promising thermally
      targeted carrier. Further examination of the in vivo biodistribution and efficacy
      will provide the necessary data to advance ELP technology toward the ultimate
      goal of human therapeutics.

PMID- 18318657
TI  - Integrating diverse data for structure determination of macromolecular
      assemblies.
AB  - To understand the cell, we need to determine the macromolecular assembly
      structures, which may consist of tens to hundreds of components. First, we review
      the varied experimental data that characterize the assemblies at several levels
      of resolution. We then describe computational methods for generating the
      structures using these data. To maximize completeness, resolution, accuracy,
      precision, and efficiency of the structure determination, a computational
      approach is required that uses spatial information from a variety of experimental
      methods. We propose such an approach, defined by its three main components: a
      hierarchical representation of the assembly, a scoring function consisting of
      spatial restraints derived from experimental data, and an optimization method
      that generates structures consistent with the data. This approach is illustrated
      by determining the configuration of the 456 proteins in the nuclear pore complex
      (NPC) from baker's yeast. With these tools, we are poised to integrate structural
      information gathered at multiple levels of the biological hierarchy--from atoms
      to cells--into a common framework.

PMID- 18318659
TI  - Diverse roles for chloroplast stromal and thylakoid-bound ascorbate peroxidases
      in plant stress responses.
AB  - Photosynthetic light reactions comprise a significant source of hydrogen peroxide
      (H(2)O(2)) in illuminated leaves. APXs (ascorbate peroxidases) reduce H(2)O(2) to
      water and play an important role in the antioxidant system of plants. In the
      present study we addressed the significance of chloroplast APXs in stress
      tolerance and signalling in Arabidopsis thaliana. To this end, T-DNA (transfer
      DNA) insertion mutants tapx, sapx and tapx sapx, lacking the tAPX (thylakoid
      bound APX), sAPX (stromal APX) or both respectively, were characterized. Photo
      oxidative stress during germination led to bleaching of chloroplasts in sapx
      single-mutant and particularly in the tapx sapx double-mutant plants, whereas the
      greening process of wild-type and tapx plants was only partially impaired. Mature
      leaves of tapx sapx double mutants were also susceptible to short-term photo
      oxidative stress induced by high light or methyl viologen treatments. After a 2
      week acclimation period under high light or under low temperature, none of the
      mutants exhibited enhanced stress symptoms. Immunoblot analysis revealed that
      high-light-stress-acclimated tapx sapx double mutants compensated for the absence
      of tAPX and sAPX by increasing the level of 2-cysteine peroxiredoxin.
      Furthermore, the absence of tAPX and sAPX induced alterations in the
      transcriptomic profile of tapx sapx double-mutant plants already under quite
      optimal growth conditions. We conclude that sAPX is particularly important for
      photoprotection during the early greening process. In mature leaves, tAPX and
      sAPX are functionally redundant, and crucial upon sudden onset of oxidative
      stress. Moreover, chloroplast APXs contribute to chloroplast retrograde
      signalling pathways upon slight fluctuations in the accumulation of H(2)O(2) in
      chloroplasts.

PMID- 18318658
TI  - Toward a control theory analysis of aging.
AB  - Aging is due to the accumulation of damage over time that affects the function
      and survival of the organism; however, it has proven difficult to infer the
      relative importance of the many processes that contribute to aging. To address
      this, here we outline an approach that may prove useful in analyzing aging. In
      this approach, the function of the organism is described as a set of interacting
      physiological systems. Degradation of their outputs leads to functional decline
      and death as a result of aging. In turn, degradation of the system outputs is
      attributable to changes at the next hierarchical level down, the cell, through
      changes in cell number or function, which are in turn a consequence of the
      metabolic history of the cell. Within this framework, we then adapt the methods
      of metabolic control analysis (MCA) to determine which modifications are
      important for aging. This combination of a hierarchical framework and the
      methodologies of MCA may prove useful both for thinking about aging and for
      analyzing it experimentally.

PMID- 18318660
TI  - A cyclic peptidylic inhibitor of murine urokinase-type plasminogen activator:
      changing species specificity by substitution of a single residue.
AB  - uPA (urokinase-type plasminogen activator) is a potential therapeutic target in a
      variety of pathological conditions, including cancer. In order to find new
      principles for inhibiting uPA in murine cancer models, we screened a phage
      displayed peptide library with murine uPA as bait. We thereby isolated several
      murine uPA-binding peptide sequences, the predominant of which was the disulfide
      bridged constrained sequence CPAYSRYLDC, which we will refer to as mupain-1. A
      chemically synthesized peptide corresponding to this sequence was found to be a
      competitive inhibitor of murine uPA, inhibiting its activity towards a low
      molecular-mass chromogenic substrate as well as towards its natural substrate
      plasminogen. The K(i) value for inhibition as well as the K(D) value for binding
      were approx. 400 nM. Among a variety of other murine and human serine proteases,
      including trypsin, mupain-1 was found to be highly selective for murine uPA and
      did not even measurably inhibit human uPA. The cyclic structure of mupain-1 was
      indispensable for binding. Alanine scanning mutagenesis identified Arg(6) of
      mupain-1 as the P1 residue and indicated an extended binding interaction
      including the P5, P3, P2, P1 and P1' residues of mupain-1 and the specificity
      pocket, the catalytic triad and amino acids 41, 99 and 192 located in and around
      the active site of murine uPA. Exchanging His(99) of human uPA by a tyrosine
      residue, the corresponding residue in murine uPA, conferred mupain-1
      susceptibility on to the latter. Peptide-derived inhibitors, such as mupain-1,
      may provide novel mechanistic information about enzyme-inhibitor interactions,
      provide alternative methodologies for designing effective protease inhibitors,
      and be used for target validation in murine model systems.

PMID- 18318661
TI  - Activation of the insulin receptor (IR) by insulin and a synthetic peptide has
      different effects on gene expression in IR-transfected L6 myoblasts.
AB  - Single-chain peptides have been recently produced that display either mimetic or
      antagonistic properties against the insulin and IGF-1 (insulin-like growth factor
      1) receptors. We have shown previously that the insulin mimetic peptide S597
      leads to significant differences in receptor activation and initiation of
      downstream signalling cascades despite similar binding affinity and in vivo
      hypoglycaemic potency. It is still unclear how two ligands can initiate different
      signalling responses through the IR (insulin receptor). To investigate further
      how the activation of the IR by insulin and S597 differentially activates post
      receptor signalling, we studied the gene expression profile in response to IR
      activation by either insulin or S597 using microarray technology. We found
      striking differences between the patterns induced by these two ligands. Most
      remarkable was that almost half of the genes differentially regulated by insulin
      and S597 were involved in cell proliferation and growth. Insulin either
      selectively regulated the expression of these genes or was a more potent
      regulator. Furthermore, we found that half of the differentially regulated genes
      interact with the genes involved with the MAPK (mitogen-activated protein kinase)
      pathway. These findings support our signalling results obtained previously and
      confirm that the main difference between S597 and insulin stimulation resides in
      the activation of the MAPK pathway. In conclusion, we show that insulin and S597
      acting via the same receptor differentially affect gene expression in cells,
      resulting in a different mitogenicity of the two ligands, a finding which has
      critical therapeutic implications.

PMID- 18318662
TI  - Genetic variation in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP)
      is associated with myocardial infarction in the German population.
AB  - Genetic variation in the genes ALOX5AP (arachidonate 5-lipoxygenase-activating
      protein) and LTA4H (leukotriene A4 hydrolase) has previously been shown to
      contribute to the risk of MI (myocardial infarction) and stroke in Icelandic and
      Scottish populations. Both genes encode proteins playing a role in the synthesis
      of the pro-inflammatory leukotriene B mediators, possibly providing a link
      between MI and inflammation. The aim of the present study was to investigate
      whether these associations could be confirmed in a large study of German MI
      patients. Two previously described four SNP (single nucleotide polymorphism)
      haplotypes of the ALOX5AP gene (termed haplotype A and B) and one SNP (rs2660899)
      of the LTA4H gene conferring the greatest risk of MI in previous studies were
      genotyped in 1211 unrelated MI cases from the German MI Family Study and in 1015
      healthy married-in spouses serving as controls. Haplotype B in the ALOX5AP gene
      was associated with an increased risk of MI in the German population, confirming
      previously reported associations of this haplotype with CAD (coronary artery
      disease) in populations from Scotland and Italy. No association with the risk of
      MI was detected for haplotype A of the ALOX5AP gene or for SNP rs2660899
      representing the LTA4H gene. In conclusion, haplotype B of the ALOX5AP gene is
      associated with an increased risk of MI in a large German study. The present
      study is the third independent report from a European population describing an
      increased risk of CAD for carriers of haplotype B of the ALOX5AP gene, which
      substantiates further a role of this gene in the pathogenesis of CAD in
      Europeans.

PMID- 18318663
TI  - Junction ribonuclease: a ribonuclease HII orthologue from Thermus thermophilus
      HB8 prefers the RNA-DNA junction to the RNA/DNA heteroduplex.
AB  - The genome of an extremely thermophilic bacterium, Thermus thermophilus HB8,
      contains a single ORF (open reading frame) encoding an RNase-HII-like sequence.
      Despite the presence of significant amino acid sequence identities with RNase
      (ribonuclease) HII enzymes, the ORF TTHA0198 could not suppress the temperature
      sensitive growth defect of an RNase-H-deficient Escherichia coli mutant and the
      purified recombinant protein could not cleave an RNA strand of an RNA/DNA
      heteroduplex, suggesting that the TTHA0198 exhibited no RNase H activity both in
      vivo and in vitro. When oligomeric RNA-DNA/DNAs were used as a mimic substrate
      for Okazaki fragments, however, the protein cleaved them only at the 5' side of
      the last ribonucleotide at the RNA-DNA junction. In fact, the TTHA0198 protein
      prefers the RNA-DNA junction to the RNA/DNA hybrid. We have referred to this
      activity as JRNase (junction RNase) activity, which recognizes an RNA-DNA
      junction of the RNA-DNA/DNA heteroduplex and cleaves it leaving a mono
      ribonucleotide at the 5' terminus of the RNA-DNA junction. E. coli and
      Deinococcus radiodurans RNases HII also cleaved the RNA-DNA/DNA substrates at the
      same site with a different metal-ion preference from that for RNase H activity,
      implying that the enzymes have JRNase activity as well as RNase H activity. The
      specialization in the JRNase activity of the RNase HII orthologue from T.
      thermophilus HB8 (Tth-JRNase) suggests that the JRNase activity of RNase HII
      enzymes might be independent of the RNase H activity.

PMID- 18318664
TI  - University of Sarajevo Medical Faculty - 60 years of continuous work.

PMID- 18318665
TI  - Inhibition of hepatitis C virus (HCV) core protein- induced cell growth by non
      structural protein 4A (NS4A) is mediated by mitochondrial dysregulation.
AB  - Hepatitis C virus (HCV) is a significant health problem facing the world. More
      than 170 million people are infected with HCV worldwide. HCV encodes a large
      polyprotein precursor that is processed into at least 10 distinct products
      including structural (core, E1 and E2) and non-structural (NS2, NS3, NS4A, NS4B,
      NS5A and NS5B). Besides its importance in virus replication, NS4A functions as a
      cofactor for NS3 and contributes to viral pathogenesis by influencing cellular
      functions. Here, we investigated the effect of NS4A protein on the growth rate
      induced by core protein in liver cells. Using our established tetracycline
      inducible system, we demonstrated the ability of NS4A protein to inhibit core
      protein-induced cell growth in Hepatoma cell line, HepG2. Induction of both core
      and NS4A proteins in HepG2-core/NS4A transfectants inhibited core-induced growth
      advantage in HepG2-core transfectants and blocked NS4A protein-induced cell
      growth inhibition in HepG2-NS4A transfectants. Using both immune fluorescence
      staining and Western blot analysis, we confirmed the localization of NS4A protein
      to the mitochondria in HepG2-NS4A transfectants expressing NS4A protein. Data
      obtained from flow cytometry analysis, using JC-1 demonstrated the loss of
      mitochondrial membrane potential (DeltaPsim) by the expression of NS4A protein in
      HepG2-NS4A transfectants, but not by the expression of core protein in HepG2-core
      transfectants. Whereas, the induction of the expression of both core and NS4A
      proteins in HepG2-core/NS4A transfectants blocked NS4A-induced loss of DeltaPsim
      in HepG2 cells. Taken together, our data suggest an important role for
      mitochondria in the modulation HCV NS4A-induced inhibition of HCV core-mediated
      cell growth.

PMID- 18318666
TI  - Direct immunofluorescence and immunohistochemistry in diagnostics of
      glomerulonephritis.
AB  - The needle biopsies from 60 transplanted and native kidneys have been processed
      and a prospective analysis of pattern, intensity and distribution of
      immunoglobulin deposits (IgA, IgG and IgM) and complement components (C3c and
      C1q) identified in these lesions has been carried out by immunohistochemistry
      with three step immunoperoxidase, in the period from 2000 to 2004. Those deposits
      were previously detected and analyzed by immunofluorescence. The samples
      consisted of 30 renal biopsies, previously diagnosed with glomerulonephritis and
      positive immunofluorescence and 30 renal biopsies without morphologic changes and
      deposits on immunofluorescence. 78,7% of the analyzed samples showed the
      identical results of the deposits of immunoglobulin and components of the
      complement with both, immunohistochemistry and immunofluorescence method.
      Sensitivity of the immunohistochemistry method with three step immunoperoxidase
      for all analyzed immunoglobulin and complement components is high (0,93), while
      specificity for the same method is 0,79. Standardized method of the three step
      immunoperoxidase on the paraffin embedded, formalin fixed needle renal biopsies
      could successfully replace the immunofluorescence method in diagnostic of GN,
      with the emphasis on a follow up and control of each single step in the procedure
      of the method.

PMID- 18318667
TI  - Influence of posttraumatic stress disorder of the fathers on other family
      members.
AB  - The purpose of this work is to analyze the frequency of depression and anxiety
      and children behaviour in families whose heads of the family (father) suffer from
      post-traumatic stress disorder (PTSD). The study was conducted from September
      2005 until July 2006, with patients living in Mostar. The frequency of depression
      and anxiety in family members older than 18 years, and changes of the behaviour
      in children younger than 18 years of age were measured. The data were collected
      from 60 men and their families who had been diagnosed with PTSD by their
      psychiatrist. The control group was formed using matching criteria (age of the
      head of the family, his education, religion, family income and number of
      children). In this study, three questionnaires were used: one specially designed
      for this study, covering general information about family members, and a personal
      opinion of each family member about the family situation and relations within the
      family; Hopkins symptoms checklist - 25 (HSCL-25) for evaluation of depression
      and anxiety for subjects older than 18; and General Health Questionnaire (GHQ)
      for children 5 to 18 years of age, which was completed by their mothers. More
      wives from the PTSD families had depression than wives from the controlled group
      (chi2=21,099; df=1; P<0,050). There was no difference between groups in frequency
      of depression and anxiety (chi2=0,003; df=1; P=0,959) for children older than 18
      years. No difference in answers between groups of children younger than 18 years
      were found in the General Health Questionnaire. However, we found significant
      differences in separate questions. Mothers, who filled the questionnaire form,
      reported that children from fathers who had PTSD experienced stomach pain more
      often (chi2=10,474;df=2; P=0,005), eating problems (chi2=14,204;df=2; P=0,001)
      and breathing problems (chi2=9,748;df=2; P=0,008), than children from fathers who
      did not have PTSD. Children from fathers with PTSD were more easily upset
      (chi2=7,586; df=2; P=0,023) and worried more often (chi2=12,093; df=2; P=0,002),
      they were also more aggressive towards other children (chi2=6,156; df=1;
      P=0,013). The controlled group of children who wanted to help with the house work
      was larger than the tested group (chi2=10,383; df=2; P=0,006). More children from
      the controlled group missed school than from the other group of surveyed children
      (chi2=6,056; df=2; P=0,048). A significantly larger number of women, whose
      husbands had PTSD, were depressed, unlike women whose husbands were not ill.
      There was no significant difference in depression manifestation in a group of
      children older than 18, as well as in behaviour of a group of children younger
      than 18, but significant differences in some provided answers were found, that
      indicate the differences between controlled and tested groups.

PMID- 18318668
TI  - Brucellosis of ruminants in Bosnia and Herzegovina: disease status, past
      experiences and initiation of a new surveillance strategy.
AB  - The current animal health situation in Bosnia and Herzegovina requires the
      prioritization of diseases for the application of control measures. One of the
      diseases requiring high priority is brucellosis of ruminants. Brucellosis is a
      zoonotic infectious disease and one of the most important zoonoses in the world.
      Brucellosis has been recognized during the past five decades as an important
      infectious disease in ruminants in Bosnia and Herzegovina. Control and
      eradication of brucellosis in animals is based on test and slaughter control
      policy. When the existing brucellosis control program was instituted, the
      veterinary and animal production sector was almost exclusively owned by the
      government, an arrangement that promoted compliance with the program and resulted
      in the successful control of the disease. This paper provides an overview of the
      current institutional and legislative framework for brucellosis control including
      the laboratory detection system and the epidemiological status of brucellosis in
      ruminants in Bosnia and Herzegovina. Relevant data were collected during the
      period spanning from the beginning of 2001 until the middle of 2007. Data we
      collected reveal an increase in the number of reported outbreaks in ruminants as
      well as a related increase in the number of human cases. This has brought serious
      consequences to public health, animal health and production and international
      trade.

PMID- 18318669
TI  - Complementarity of standard cytogenetic assays.
AB  - Standard cytogenetic assays used in genotoxicology usually include chromosome
      aberrations analysis and micronucleus cytokinesis-block assay. Both tests
      originate on standard protocol for lymphocyte culture and can be used as
      complement or substitute to each other. Aim of this study was to evaluate
      complementarities between results of chromosome aberration analysis assay and
      results of micronucleus cytokinesis-block assay in representative sample of
      inhabitants from Bosnia and Herzegovina. The aim was achieved by calculating
      Pearson correlation coefficient and simple linear regression.

PMID- 18318670
TI  - Urinary hippuric acid after ingestion of edible fruits.
AB  - Aim of this study was to evaluate the biotransformation of simple phenols after
      ingestion of edible fruits and mixed food. It was analyzed hippuric acid in urine
      as biomarker of conjugation in the liver cells of glycine with aromatic phenolic
      acids such benzoic and salicylic acid from ingested food. Measurement of hippuric
      acid in urine samples of 10 healthy individuals: 5 female and 5 male with a mean
      age 51,5 years were recruited to participate in this study. Urine samples were
      collected for 24 hours. The additional meals 300 g of fruits: blueberry, cherry,
      raspberry, melon, blackberry and mixed food were given immediately before the 24
      hr urine sampling. Otherwise, the meals given during 24 hr was a usually food.
      Biotransformation of phenols in edible fruits, that are together with liver
      glycins precursors of hippuric acid biosynthesis, was evaluated by direct
      spectrophotometric measurement of excreted hippuric acid in urine at 410 nm. It
      was established that the highest quantity of hippuric acid was after ingestion of
      300 g of bilberry fruits (p< 0,003), and same quantity of cherries (p< 0,003).
      Concentration of excreted hippuric acid was twice higher after ingestion of these
      fruits in comparison with hippuric acid concentrations in urine after ingestion
      of common - mixed food. Quantity of biosynthesised hippuric acid was in direct
      correlation with the concentrations of its precursors, primarily phenol acids and
      other simple aromatic acids ingested with food.

PMID- 18318671
TI  - Should diagnostic hysteroscopy be a routine procedure during diagnostic
      laparoscopy in infertile women?
AB  - The aim of this study was to clarify the role of simultaneous combined diagnostic
      approach using laparoscopy and hysteroscopy in the evaluation of female
      infertility. In a retrospective study, 360 infertile women underwent complete
      fertility evaluation. All the patients were examined by simultaneous combined
      laparoscopy and hysteroscopy as a part of the routine infertility evaluation.
      Laparoscopy and hysteroscopy were successful in 360 patients. Bilateral tubes
      were blocked in 18 (5%) and unilateral tubal occlusion were in 30 (8,33%) of
      patients. Pelvic adhesions were revealed in 40 (11,11%), and myomas in 42
      (11,65%) out of that 31 (8,6%) were revealed by laparoscopy and 11 (3,05%) by
      hysteroscopy. Endometrial polyps were revealed in 26 (7,22%) and Syndrome
      Asherman in 3(0,83%) of patients. Uterine anomaly was found in 19 (5,27%) of
      cases and out of that septate uterus in 7 (37,15%), bicornuate uterus in 5
      (26,31%), arcuate uterus in 4 (21,26%) and uterus unicornu cum cornu rudimentario
      in 3 (15,27%) of uterine anomalies. Endometriosis was found in 51 (14,16%),
      dermoid cysts in 8 (2,22%) and in 16 (4,44%) functional cysts of patients. Also,
      Fitz-Hugh-Curtis syndrome was revealed in 23 (6,11%) of our patients. Laparoscopy
      and hysteroscopy play very important role as diagnostic tools in the infertility
      women. Combined diagnostic simultaneous laparoscopy and hysteroscopy should be
      performed in all infertile patients before the treatment.

PMID- 18318672
TI  - Postoperative glycaemia in patients following the CABG surgery.
AB  - In this study we analyzed patients glucose levels taken before and after coronary
      artery bypass surgery. The data are taken from University of Sarajevo Clinics
      Centre- medical documentation of Heart Center from January 1st, 2007 to October
      31st, 2007. Therefore, the entire study is done retrospectively. The patients
      considered in this analysis were divided into three groups. The patients in the
      first group were treated with peroral antidiabetics. The second group included
      patients treated with insulin while the third group consisted of patients without
      diabetes and acted as control group. All the patients had increased BMI. In the
      first two groups glucose levels were elevated before the surgery. Data analysis
      showed that three patients from the first group changed from peroral
      antidiabetics to insulin during postoperative period, and they were dismissed
      from hospital with this therapy. In the control group, peroral antidiabetis were
      introduced in four patients. The study results show that all the three groups
      have had high glycaemia on the first postoperative day. This may be caused by a
      number of reasons: inadequate pre-operative antidiabetic therapy, the impact of
      stress during surgery, inadequate pre-operative treatment of glycaemia or
      avoidance of the proscribed therapy by patients themselves. Stress during
      operation and administration of several medications after operation may also
      cause increased insulin resistance and distort glycaemia control.

PMID- 18318673
TI  - More than ten years of DOTS in Bosnia and Herzegovina.
AB  - Directly Observed Therapy Short-course (DOTS) is composed of five distinct
      elements: political commitment, case detection through quality-assured
      bacteriology; drug supplies; surveillance and monitoring systems and use of
      highly efficacious regimens; and direct observation of treatment. DOTS produces
      cure rates of up to 95 percent even in the poorest countries and prevents the
      development of Multi-Drug Resistant Tuberculosis. National TB Programme (NTP) has
      been started to introduce in 1994 according to DOTS principles in B&H with
      central and regional levels. At central levels there are national TB
      coordinators, and in all Cantons/Regions there are regional TB Coordinators.
      During intensive phase of therapy, patients are hospitalized. In the second phase
      of therapy, patients are treated in anti-tuberculosis dispensaries and some of
      them by a responsible member of the family (family supervision). There are
      several weaknesses in implementation of DOTS in B&H: TB case detection was not
      fully implemented in all medical services. Registration of TB cases in some
      facilities, there is no official central recommended registry, individual
      reporting for treatment outcomes and establishing a reliable monitoring and
      evaluation system. Application for 6 round of The Global Fund to Fight AIDS, TB
      and Malaria (GFATM) had been finally approved and signed for B&H in October 2007.
      These grants would repair some implementation gaps and improve DOTS strategy in
      B&H.

PMID- 18318674
TI  - The effects of antenatal corticosteroid treatment on IVH-PVh of premature
      infants.
AB  - Intraventricular-periventricular hemorrhage (IVH-PVH) is the most frequent type
      of intracranial hemorrhage in premature infants and the major cause of
      neurodevelopmental disabilities in children too. The objective of this work is to
      evaluate the effects of prenatal corticosteroid treatment on the incidence of IVH
      PVH in premature infants. The study enrolled 163 prematures of 26-34 weeks'
      gestation. They have been divided into two groups: the experimental group
      (80/163), who have been treated with corticosteroids prenatally and control group
      (83/163), who have not received such treatment. There is statistically
      significant difference in IVH-PVH incidence between the experimental group
      (18/80) and control group (32/83) (chi2 =5,616, p<0,05). There is no
      statistically significant difference in Apgar score after 5 minutes between the
      experimental group and control group of IVH-PVH prematures, t= 0,121. There is no
      statistically significant difference in mean gestation age between the
      experimental group (30,74 weeks) and control group (29,97 weeks) of IVH-PVH
      prematures, t= 1,299. There is no statistically significant difference in mean
      birth weight between the experimental group (1479,44 grams) and control group
      (1379,37 grams) of IVH-PVH prematures, t= 0,913. Antenatal corticosteroid
      treatment of premature infants reduced the incidence of IVH-PVH significantly.
      There is no statistically significant difference in Apgar score after 5 minutes,
      mean gestation age and mean birth weight between the experimental and control
      group of IVH PVH prematures.

PMID- 18318675
TI  - Scanning near-field optical microscopy.
AB  - An average human eye can see details down to 0,07 mm in size. The ability to see
      smaller details of the matter is correlated with the development of the science
      and the comprehension of the nature. Today's science needs eyes for the nano
      world. Examples are easily found in biology and medical sciences. There is a
      great need to determine shape, size, chemical composition, molecular structure
      and dynamic properties of nano-structures. To do this, microscopes with high
      spatial, spectral and temporal resolution are required. Scanning Near-field
      Optical Microscopy (SNOM) is a new step in the evolution of microscopy. The
      conventional, lens-based microscopes have their resolution limited by
      diffraction. SNOM is not subject to this limitation and can offer up to 70 times
      better resolution.

PMID- 18318676
TI  - The results of Hodgkin lymphoma treatment in children in the period 1997-2006.
AB  - In this paper we present the study of chemotherapy and radiotherapy treatment
      success in children suffering from Hodgkin's disease (HD) that were treated at
      Hematology-oncology Department of Pediatric Clinic in Sarajevo. In retrospective
      study we followed all patients with HD aged 0-15 who were diagnosed with and
      treated for HD at Pediatric Clinic in Sarajevo over the last 10 years (1st of
      January 1997 - 31st of December 2006). Until 2000 we used combination of
      chemotherapy and radiotherapy according to UKCCSG HD 9201 treatment protocol, and
      after the year 2000 protocol UKCCSG HD 2000 (ChlVPP / ABVD) was applied. The
      total number of the treated children 33. There were 17 boys (51,51 %) and 16
      girls (48,49 %). In 10 patients (30,3 %) we found II A stage of HD, in 4 (12,1 %)
      II B stage of HD, in 6 children (18,8 %) stage III A, in 4 children (12,1 %)
      stage III B, in 4 children (12,1 %) stage IV A and in 5 (15,1 %) stage IV B. In 7
      patients (21,2 %) relapse occurred, which demanded more aggressive
      chemotherapeutic treatment and radiotherapy too; while for 4 patients (12,1 %) in
      combination with bone marrow transplantation. Three patients (9,0 %) died. There
      are 30 children (91,0 %) who are alive and in either 1st or 2nd remission phase
      of HD. Secondary malignancies did not occur in any of the patients. Although many
      patients (58,1%) were diagnosed in an advanced stage of illness (III and IV) the
      results of HD therapy at Pediatric Clinic in Sarajevo are comparable to those in
      other European centers.

PMID- 18318677
TI  - Paroxetine in the treatment of post traumatic stress disorder: our experiences.
AB  - Posttraumatic stress disorder can develop after individual's exposure or
      witnessing of life threatening events. It is characterized by three clusters of
      symptoms. The course of PTSD is often chronic and impedes individual's
      functioning. Studies of PTSD treatment with paroxetine provide evidence for its
      efficacy in reducing symptoms and its favorable profile of side-effects. The
      objective of this work was to determine the efficacy of paroxetine in the
      treatment of PTSD. The sample consisted of 30 subjects with chronic PTSD. All
      subjects received treatment with paroxetine in therapeutic dose range for six
      months. Subjects were assessed prior to therapy and following six months of
      treatment with paroxetine with the use of following instruments: SCL 90-R,
      Mississippi Questionnaire, and CGI. The results indicate statistically
      significant reduction on all subscales of SCL 90-R following six months of
      treatment, P<0,05. The difference between two assessments with Mississippi
      Questionnaire was statistically significant, P< 0,05. PTSD rate in our sample was
      reduced from 100% before treatment to 64% after treatment. Paroxetine was
      administered in daily dose of 20 mg in 88% of the subjects, and 40 mg in the
      remaining 12%. Unwanted effects were registered in 16,7% of the subjects and they
      were mild. Objective improvement was registered in 84% of the sample, and
      subjective improvement was registered in 80%. Reduction of relapse symptoms was
      registered in 24% of the subjects. Paroxetine proved to be efficient and safe in
      treatment of symptoms of PTSD in this study.

PMID- 18318678
TI  - Some aspects of balance disorder in patients with multiple sclerosis.
AB  - The aim of this study was to analyze: frequency of balance disorder (vertigo and
      disequilibrium), frequency of abnormalities in auditory evoked potentials (AEP)
      and magnetic resonance imaging (MRI) changes of the brain in multiple sclerosis
      (MS) patients with balance disorder, relation of patient's disability status to
      balance disorder and relation of the changes in MRI of the brainstem to AEP
      abnormalities. It was analyzed 60 patients with relapsing-remitting form of MS.
      Two groups of patients were made consecutively under Expanded Disability Status
      Scale score (EDSS): A (EDSS < or =4,5) and B (EDSS > or =5,0). The study was
      retrospective-prospective. After the neurological exam AEP and MRI of the brain
      have been done. Balance disorder has been verified as initial symptom in 29
      (48,4%) and out of them disequilibrium experienced 24 (83,4%) patients. During
      the relapses balance disorder experienced 48 (80%) patients and in 37 (77,1%) it
      was disequilibrium. Among them 33 (68,7%) were with lower EDSS (< or =4,5) and 15
      (31,3%) with higher EDSS score (> or =5). There is no correlation between
      disability status and vertigo which means that vertigo is not more frequent in
      more disabled patients and vice-versa. The AEP were pathological in 57 (95%)
      patients. Of all 29 patients with vertigo AEP were pathological in 28 (96,5%)
      while in 31 patients without vertigo pathological AEP were in 29 (93,5%) but it
      is not statistical significant. The most frequent characteristic of AEP changes
      were prolonged inter-peak latency III-V waves (48 patients or 80%). The plaque in
      brainstem visualized by MRI was found in 41 (71,8%) of patients (38 or 92,6% of
      them had pathological AEP and in three patients AEP were normal). In group of
      patients with pathological AEP, 38 (66,6%) of them had plaque in brainstem. In
      other three patients with normal AEP it was visualized plaque in brainstem. In
      the group of 29 patients with balance disorder, 20 (68,9%) had plaque in
      brainstem as well as 21 (67,7%) out of 31 patients without balance disorder had
      plaque in the brainstem. This difference is not statistical significant. It is
      concluded that the vertigo (including disequilibrium) is relatively often (48,4%)
      initial symptom of MS. Vertigo is not more frequent in patients with higher EDSS
      score and vice-versa. Pathological AEP are frequent neurophysiologic finding in
      both (95%) patients with (96,5%) and without (93,5%) vertigo. The most often
      pathological characteristic of AEP are prolonged interpeak latency of III-V waves
      (78,5%), as well as abnormalities of V and than IV wave. MS plaques in brainstem
      visualized by MRI technique are frequent in both groups of patients with and
      without pathological finding of the AEP.

PMID- 18318679
TI  - Correlation of autoantibodies presence detected by IFA-anti-dsDNA, IFA-AMA and
      immunoblotting with corresponding data in clinical management of autoimmune
      diseases.
AB  - Diagnosis and management of patients with SLE (Systemic Lupus Eritematosus),
      autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), involves specific
      diagnostic tests, such as IFA-AMA, IFA anti-dsDNA and immunoblotting for the
      detection of autoantibodies for specific autoantigens (mitochondria, dsDNA, M2,
      LKM-1, LC-1, SLA/LP). We established specific correlation between the detected
      autoantibodies and corresponding clinical findings. The total of 813 serum
      specimens were probed with IFA-anti-dsDNA, 98 of which tested positive. We also
      performed dilution analysis to the end point for all the positive specimens.
      Numerous specimens were tested by IFA, AMA and immunoblotting.

PMID- 18318680
TI  - Stability of cefuroxime axetil oral suspension at different temperature storage
      conditions.
AB  - Stability testing of an active substance or finished product provides information
      of the variation of drug substance or final product with time influenced by a
      variety of environmental factors such as temperature, humidity and light.
      Knowledge gained from stability studies enables understanding of the effects of
      the environment on the drugs. The aim of our study was to determine the stability
      of cefuroxime axetil oral suspension at different temperature storage conditions
      (stored at room /20 degrees C/ and refrigerated /5 degrees C/ conditions).
      Determination of cefuroxime (as cefuroxime axetil) was performed by dissolution
      testing. Fractions of the released cefuroxime axetil were compared using f2
      value. After interpolating data for dissolution profiles at room and refrigerated
      conditions the following f2values were obtained: 62,56; 56,32 and 36,18 on 3rd,
      6th and 10th day, respectively. These values indicate similarities in drug
      release from analyzed cefuroxime axetil oral suspension on 3rd, 6th day, and
      differences on 10th day. Based on our results, we may assume that cefuroxime
      axetil oral suspension preserves its stability for 10 days after reconstitution
      under room and refrigerated conditions. It is obvious, according to the f2 value
      obtained on the 10th day, that there is a difference between the released
      cefuroxime axetil from oral suspension at room (87,68%) and refrigerated (92,35%)
      conditions. Concentration changes can be caused by the mechanisms associated with
      drug release and hydrolytical decomposition of the sample and higher temperatures
      during longer period of storage.

PMID- 18318681
TI  - Leo stent-assisted coil embolization of a giant middle cerebral artery aneurysm.
AB  - We report a case of a 70-year-old man harboring a wide-necked thrombosed giant
      aneurysm of the left middle cerebral artery (MCA) on the M1 segment. The patient
      presented with generalized tonic-clonic seizures. A computerized tomography scan
      showed a calcified aneurysmal wall with perianeurysmal swelling. The aneurysm was
      successfully embolized using closed-cell nitinol stent-assisted coiling (Leo,
      BALT Co., Montmorency, France).

PMID- 18318682
TI  - The value of diffusion-weighted imaging in the diagnosis of Marchiafava-Bignami
      disease: apropos of a case.
AB  - Marchiafava-Bignami disease (MBD) is characterized by demyelination and necrosis
      of corpus callosum encountered in chronic alcoholic patients. Etiology is the
      deficiency of vitamin B complex. Magnetic resonance imaging (MRI) in MBD
      typically reveals focal lesions of high T2 and FLAIR signal intensity in the
      corpus callosum. We here present a 42-year-old male alcoholic diagnosed as MBD on
      the basis of MRI and diffusion-weighted imaging (DWI) features. The patient
      totally recovered following appropriate vitamin B complex replacement therapy,
      despite reduced diffusion in the initial setting. This case report emphasizes on
      the important role played by MRI and DWI in the early diagnosis and follow-up of
      this potentially fatal disease.

PMID- 18318683
TI  - Novel applications of magnetic resonance imaging to image tissue inflammation
      after stroke.
AB  - Experimental studies suggest that stroke-induced brain damage progresses during
      subacute stages. Cerebral ischemic injury is associated with the induction of a
      series of inflammatory events, including the infiltration of circulating immune
      cells and activation of resident cells. Local brain inflammation is
      spatiotemporally related to the occurrence of delayed apoptotic cell death.
      Therefore, ischemia-associated inflammation may not only play a major role in the
      pathogenesis of neurodegeneration associated with stroke, but may also mediate
      beneficial effects such as lesion demarcation, wound healing, and tissue
      regeneration especially via secretion of nerve growth factors. In this context,
      noninvasive imaging of inflammation associated with ischemic stroke lesions could
      have a predictive value and may be helpful for the development of cytoprotective
      drugs.

PMID- 18318684
TI  - Multi-site phasic neural activity mediates the execution of an auditory
      continuous performance task: a PET and electrophysiological study.
AB  - BACKGROUND AND PURPOSE: We studied an auditory continuous performance task with
      positron emission tomography (PET) and EEG-derived current density
      reconstructions (CDRs) to define the spatial and temporal aspects of auditory
      attention. METHODS: The CDRs were employed to segregate responses to targets and
      non-targets at sites identified by PET. We then studied the time course of brain
      activity using statistical parametric mapping (SPM) of the CDR data. RESULTS: In
      contrast to target EEG activity, non-targets did not produce significant peaks
      after 300 ms. Pre-300 ms biphasic activation of auditory, left posterior frontal,
      left supplemental, and primary motor cortices and the anterior cingulate (AC) and
      biphasic suppression of posterior cingulate and occipital cortex were identical
      for targets and non-targets and may mediate the target non-target decision. SPM
      analysis of post-300 ms CDRs showed cingulate cortices were the first to be
      reactivated, remained active through 672 ms, and were accompanied by reactivation
      and deactivation of the same sites observed in the pre-P300 responses.
      CONCLUSIONS: The cingulate may play an important role in post-decisional activity
      and control activity at other sites involved in post-decisional cognitive
      processing.

PMID- 18318685
TI  - Mitochondrial respiratory pathways modulate nitrate sensing and nitrogen
      dependent regulation of plant architecture in Nicotiana sylvestris.
AB  - Mitochondrial electron transport pathways exert effects on carbon-nitrogen (C/N)
      relationships. To examine whether mitochondria-N interactions also influence
      plant growth and development, we explored the responses of roots and shoots to
      external N supply in wild-type (WT) Nicotiana sylvestris and the cytoplasmic male
      sterile II (CMSII) mutant, which has a N-rich phenotype. Root architecture in N.
      sylvestris seedlings showed classic responses to nitrate and sucrose
      availability. In contrast, CMSII showed an altered 'nitrate-sensing' phenotype
      with decreased sensitivity to C and N metabolites. The WT growth phenotype was
      restored in CMSII seedling roots by high nitrate plus sugars and in shoots by
      gibberellic acid (GA). Genome-wide cDNA-amplified fragment length polymorphism
      (AFLP) analysis of leaves from mature plants revealed that only a small subset of
      transcripts was altered in CMSII. Tissue abscisic acid content was similar in
      CMSII and WT roots and shoots, and growth responses to zeatin were comparable.
      However, the abundance of key transcripts associated with GA synthesis was
      modified both by the availability of N and by the CMSII mutation. The CMSII
      mutant maintained a much higher shoot/root ratio at low N than WT, whereas no
      difference was observed at high N. Shoot/root ratios were strikingly correlated
      with root amines/nitrate ratios, values of <1 being characteristic of high N
      status. We propose a model in which the amine/nitrate ratio interacts with GA
      signalling and respiratory pathways to regulate the partitioning of biomass
      between shoots and roots.

PMID- 18318686
TI  - Changing transcriptional initiation sites and alternative 5'- and 3'-splice site
      selection of the first intron deploys Arabidopsis protein isoaspartyl
      methyltransferase2 variants to different subcellular compartments.
AB  - Arabidopsis thaliana (L.) Heynh. possesses two PROTEIN-L-ISOASPARTATE
      METHYLTRANSFERASE (PIMT) genes encoding enzymes (EC 2.1.1.77) capable of
      converting uncoded l-isoaspartyl residues, arising spontaneously at l-asparaginyl
      and l-aspartyl sites in proteins, to l-aspartate. PIMT2 produces at least eight
      transcripts by using four transcriptional initiation sites (TIS; resulting in
      three different initiating methionines) and both 5'- and 3'-alternative splice
      site selection of the first intron. The transcripts produce mature proteins
      capable of converting l-isoaspartate to l-aspartate in small peptide substrates.
      PIMT:GFP fusion proteins generated a detectable signal in the nucleus. However,
      whether the protein was also detectable in the cytoplasm, endo-membrane system,
      chloroplasts, and/or mitochondria, depended on the transcript from which it was
      produced. On-blot-methylation of proteins, prior to the completion of
      germination, indicated that cruciferin subunits contain isoaspartate. The
      implications of using transcriptional mechanisms to expand a single gene's
      repertoire to protein variants capable of entry into the cell's various
      compartments are discussed in light of PIMT's presumed role in repairing the
      proteome.

PMID- 18318687
TI  - AtMSH5 partners AtMSH4 in the class I meiotic crossover pathway in Arabidopsis
      thaliana, but is not required for synapsis.
AB  - MSH5, a meiosis-specific member of the MutS-homologue family of genes, is
      required for normal levels of recombination in budding yeast, mouse and
      Caenorhabditis elegans. In this paper we report the identification and
      characterization of the Arabidopsis homologue of MSH5 (AtMSH5). Transcripts of
      AtMSH5 are specific to reproductive tissues, and immunofluorescence studies
      indicate that expression of the protein is abundant during prophase I of meiosis.
      In a T-DNA tagged insertional mutant (Atmsh5-1), recombination is reduced to
      about 13% of wild-type levels. The residual chiasmata are randomly distributed
      between cells and chromosomes. These data provide further evidence for at least
      two pathways of meiotic recombination in Arabidopsis and indicate that AtMSH5
      protein is required for the formation of class I interference-sensitive
      crossovers. Localization of AtMSH5 to meiotic chromosomes occurs at leptotene and
      is dependent on DNA double-strand break formation and strand exchange.
      Localization of AtMSH5 to the chromatin at mid-prophase I is dependent on
      expression of AtMSH4. At late zygotene/early pachytene a proportion of AtMSH5
      foci co-localize with AtMLH1 which marks crossover-designated sites. Chromosome
      synapsis appears to proceed normally, without significant delay, in Atmsh5-1 but
      the pachytene stage is extended by several hours, indicative of the operation of
      a surveillance system that monitors the progression of prophase I.

PMID- 18318688
TI  - Coagulation, genotypes and recurrent cardiovascular events: what further studies
      are required?

PMID- 18318689
TI  - Prospective multicenter evaluation of the pulmonary embolism rule-out criteria.
AB  - BACKGROUND: Over-investigation of low-risk patients with suspected pulmonary
      embolism (PE) represents a growing problem. The combination of gestalt estimate
      of low suspicion for PE, together with the PE rule-out criteria [PERC(-): age <
      50 years, pulse < 100 beats min(-1), SaO(2) >or= 95%, no hemoptysis, no estrogen
      use, no surgery/trauma requiring hospitalization within 4 weeks, no prior venous
      thromboembolism (VTE), and no unilateral leg swelling], may reduce speculative
      testing for PE. We hypothesized that low suspicion and PERC(-) would predict a
      post-test probability of VTE(+) or death below 2.0%. METHODS: We enrolled
      outpatients with suspected PE in 13 emergency departments. Clinicians completed a
      72-field, web-based data form at the time of test order. Low suspicion required a
      gestalt pretest probability estimate of <15%. The main outcome was the composite
      of image-proven VTE(+) or death from any cause within 45 days. RESULTS: We
      enrolled 8138 patients, 85% of whom had a chief complaint of either dyspnea or
      chest pain. Clinicians reported a low suspicion for PE, together with PERC(-), in
      1666 patients (20%). At initial testing and within 45 days, 561 patients (6.9%,
      95% confidence interval 6.5-7.6) were VTE(+), and 56 others died. Among the low
      suspicion and PERC(-) patients, 15 were VTE(+) and one other patient died,
      yielding a false-negative rate of 16/1666 (1.0%, 0.6-1.6%). As a diagnostic test,
      low suspicion and PERC(-) had a sensitivity of 97.4% (95.8-98.5%) and a
      specificity of 21.9% (21.0-22.9%). CONCLUSIONS: The combination of gestalt
      estimate of low suspicion for PE and PERC(-) reduces the probability of VTE to
      below 2% in about 20% of outpatients with suspected PE.

PMID- 18318690
TI  - Introducing a single-cell-derived human mesenchymal stem cell line expressing
      hTERT after lentiviral gene transfer.
AB  - Human mesenchymal stem cells (hMSCs) can be readily isolated from bone marrow and
      differentiate into multiple tissues, making them a promising target for future
      cell and gene therapy applications. The low frequency of hMSCs in bone marrow
      necessitates their isolation and expansion in vitro prior to clinical use, but
      due to senescence-associated growth arrest during culture, limited cell numbers
      can be generated. The lifespan of hMSCs has been extended by ectopic expression
      of human telomerase reverse transcriptase (hTERT) using retroviral vectors. Since
      malignant transformation was observed in hMSCs and retroviral vectors cause
      insertional mutagenesis, we ectopically expressed hTERT using lentiviral gene
      transfer. Single-cell-derived hMSC clones expressing hTERT did not show malignant
      transformation in vitro and in vivo after extended culture periods. There were no
      changes observed in the expression of tumour suppressor genes and karyotype.
      Cultured hMSCs lack telomerase activity, but it was significantly increased by
      ectopic expression of hTERT. HTERT expression prevented hMSC senescence and the
      cells showed significantly higher and unlimited proliferation capacity. Even
      after an extended culture period, hMSCs expressing hTERT preserved their stem
      cells character as shown by osteogenic, adipogenic and chondrogenic
      differentiation. In summary, extending the lifespan of human mesenchymal stem
      cells by ectopic expression of hTERT using lentiviral gene transfer may be an
      attractive and safe way to generate appropriate cell numbers for cell and gene
      therapy applications.

PMID- 18318691
TI  - Epidermal growth factor receptor and cancer: control of oncogenic signalling by
      endocytosis.
AB  - The epidermal growth factor receptor (EGFR) and other members of the EGFR/ErbB
      receptor family of receptor tyrosine kinases (RTKs) are important regulators of
      proliferation, angiogenesis, migration, tumorigenesis and metastasis.
      Overexpression, mutations, deletions and production of autocrine ligands
      contribute to aberrant activation of the ErbB proteins. The signalling output
      from EGFR is complicated given that other ErbB proteins are often additionally
      expressed and activated in the same cell, resulting in formation of homo-and/or
      heterodimers. In particular, association of EGFR with ErbB2 prevents its down
      regulation, underscoring the importance of the cellular background for EGFR
      effects. Signalling from ErbB proteins can either be terminated by dissociation
      of ligand resulting in dephosphorylation, or blunted by degradation of the
      receptors. Although proteasomal targeting of ErbB proteins has been described,
      lysosomal degradation upon ligand-induced endocytosis seems to play the major
      role in EGFR down-regulation. Preclinical and clinical data have demonstrated
      that EGFR is a central player in cancer, especially in carcinomas, some brain
      tumours and in non-small cell lung cancer. Such studies have further validated
      EGFR as an important molecular target in cancer treatment. This review focuses on
      mechanisms involved in ligand-induced EGFR activation and endocytic down
      regulation. A better understanding of EGFR biology should allow development of
      more tumour-selective therapeutic approaches targeting EGFR-induced signalling.

PMID- 18318692
TI  - Stratified epithelial sheets engineered from a single adult murine corneal/limbal
      progenitor cell.
AB  - The limbal region of the adult cornea contains stem cells which are ultimately
      responsible for regeneration of the corneal epithelium during wound repair.
      However, primarily-isolated murine corneal/limbal epithelial cells rapidly
      senesce on plastic in a serum-free low [Ca(2+)] medium, suggesting only transit
      amplifying cells are promoted. We developed a novel expansion method by seeding
      at a low cell density (<500 cells/cm(2)) and prolonging each culture time beyond
      the lifespan of transit amplifying cells (4 weeks). Expanded cells were uniformly
      small, negative to K12 keratin, but positive for p63 nuclear staining, and could
      be subcultured beyond 100 passages. After limiting dilution, one clone (TKE2) was
      selected that exhibited single cell clonal expansion with a doubling time of 34.2
      hrs, and had normal karyotyping, but no anchorage-independent growth. A single
      cell could be continually expanded to a confluent monolayer on denuded amniotic
      membrane and became stratified by exposing to the air-medium interface. The
      resultant stratified epithelium expressed K14 keratin, involucrin, connexin 43
      and p63, but not K12 keratin or Pax 6. However, expression of K12 could be up
      regulated by increasing extracellular calcium concentration and addition of
      foetal bovine serum (FBS) at P12, but less so at P85. Therefore, this murine lim
      bal/corneal epithelium-derived progenitor cell line still retained the plasticity
      for adopting corneal lineage differentiation, could be useful for investigating
      limbal niche cues that may promote corneal epithelial fate decision.

PMID- 18318693
TI  - Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population
      based study.
AB  - The risk of dementia and Alzheimer's disease (AD) probably results from an
      interaction between genetic and environmental factors. The aim of this study was
      to investigate the effects and putative interactions between the apoE epsilon4
      allele and lifestyle related risk factors for dementia and AD. Participants of
      the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived
      from random, population-based samples previously studied in 1972, 1977, 1982 or
      1987. After an average follow-up of 21 years, 1449 individuals (72.5%) aged 65-79
      years were re-examined in 1998. The apoE epsilon4 allele was an independent risk
      factor for dementia/AD even after adjustments for sociodemographic, lifestyle and
      vascular factors (odds ratio [OR]=2.83, 95% confidence interval [CI]=1.61-4.97).
      Physical inactivity, alcohol drinking and smoking increased the risk of
      dementia/AD particularly among the apoE epsilon4 carriers. Furthermore, low
      moderate intake of polyunsaturated, and moderate-high intake of saturated fats
      were associated with an increased risk of dementia/AD more pronouncedly among
      apoE epsilon4 carriers. Composite effect of the lifestyle factors was
      particularly seen among the epsilon4 carriers (OR=11.42, 95% CI=1.94-67.07 in the
      4th quartile). Physical inactivity, dietary fat intake, alcohol drinking and
      smoking at midlife are associated with the risk of dementia and AD, especially
      among the apoE epsilon4 carriers. The apoE epsilon4 carriers may be more
      vulnerable to environmental factors, and thus, lifestyle interventions may
      greatly modify dementia risk particularly among the genetically susceptible
      individuals.

PMID- 18318694
TI  - Factor analysis scales of generalized amino acid information as applied in
      predicting interactions between the human amphiphysin-1 SH3 domains and their
      peptide ligands.
AB  - Factor analysis scales of generalized amino acid information (FASGAI) involving
      hydrophobicity, alpha-helix and beta-turn propensities, bulky properties,
      compositional characteristics, local flexibility, and electronic properties, was
      proposed to represent the structures of the decapeptides binding the human
      amphiphysin-1 SH3 domains. Parameters being responsible for the binding
      affinities were selected by genetic algorithm, and a quantitative structure
      affinity relationship (QSAR) model by partial least square was established to
      predict the peptide-SH3 domain interactions. Diversified properties of the
      residues between P(2) and P(-3) (including P(2) and P(-3)) of the decapeptide
      (P(4)P(3)P(2)P(1)P(0)P(-1)P(-2)P(-3)P(-4)P(-5)) may contribute remarkable effect
      to the interactions between the SH3 domain and the decapeptide. Particularly,
      electronic properties of P(2) may provide relatively large positive contributions
      to the interactions, and reversely, hydrophobicity of P(2) may be largely
      negative to the interactions. These results showed that FASGAI vectors can well
      represent the structural characteristics of the decapeptides. Furthermore, the
      model obtained, which showed low computational complexity, correlated FASGAI
      descriptors with the binding affinities as well as that FASGAI vectors may also
      be applied in QSAR studies of peptides.

PMID- 18318695
TI  - Postoperative severe uvular edema following tonsillectomy in a child with a
      history of obstructive sleep apnea.

PMID- 18318696
TI  - Effect of drinks that are added as flavoring in oral midazolam premedication on
      sedation success.
AB  - BACKGROUND: Midazolam is one of the most frequently used agents for sedation in
      pediatric dentistry. The injectable form of midazolam can also be given orally.
      However, its bad taste has negative effects on ingestion of the drug. In this
      study, we aimed to evaluate the effect of drinks which were added to mask the
      bitter taste of midazolam for drug acceptance and sedation. METHODS: In the
      laboratory; the pH values of 2.5 ml midazolam (15 mg x 3 ml(-1)) and the mixtures
      of Pepsi Cola, 10% sodium citrate, fresh pomegranate juice, and fresh grapefruit
      juice in equal volumes were measured. Seventy-five patients between 2 and 8 years
      of age who were assessed to have anxiety with the Frankl Behavior Scale and whose
      dental treatment was planned under sedation were randomly divided into five
      groups. Pepsi Cola (Group I), 10% sodium citrate (Group II), pomegranate juice
      (Group III), and grapefruit juice (Group IV) which were added to 0.75 mg x kg(-1)
      midazolam in equal volumes, and (Group V) 0.75 mg x kg(-1) midazolam given orally
      to children. The drug compliance of children was evaluated. After 15 min, 4-5 l x
      min(-1) of N(2)O : O(2) (40 : 60) inhalation was started via a nasal hood. During
      the procedure, heart rate, and SpO2 were monitored with pulse oximetry and
      sedation levels with the Ramsay Sedation Scale (RSS). Anesthetist, dentist, and
      parental satisfaction levels were recorded. RESULTS: The groups had similar
      demographics, drug ingestion was better in Groups I and II, but the mean RSS was
      the highest in Group II (P < 0.05). CONCLUSIONS: As well as making drug ingestion
      much simpler, the addition of sodium citrate to the midazolam administered orally
      to the children increased the effectiveness of sedation.

PMID- 18318697
TI  - The neglected 'm' in MCH programmes--why mental health of mothers is important
      for child nutrition.
AB  - In most societies, mothers are the primary providers of nutrition and care to
      young children. This is a demanding task, and poor physical or mental health in
      mothers might be expected to have adverse consequences on their children's
      health, nutrition and psychological well-being. Child nutrition programmes do not
      adequately address maternal mental health. In this article, we consider the
      evidence from less developed countries on whether maternal mental health
      influences child growth, with respect to evidence from both observational studies
      and from clinical trials. We estimate how much of the burden of undernutrition
      might be averted in one setting, and propose that promoting maternal mental
      health and treating maternal mental illness offer important new opportunities to
      tackle the twin scourges of maternal ill-health and child undernutrition.

PMID- 18318698
TI  - Could clinical audit improve the diagnosis of pulmonary tuberculosis in Cuba,
      Peru and Bolivia?
AB  - OBJECTIVES: To assess the effectiveness of clinical audit in improving the
      quality of diagnostic care provided to patients suspected of tuberculosis; and to
      understand the contextual factors which impede or facilitate its success.
      METHODS: Twenty-six health centres in Cuba, Peru and Bolivia were recruited.
      Clinical audit was introduced to improve the diagnostic care for patients
      attending with suspected TB. Standards were based on the WHO and TB programme
      guidelines relating to the appropriate use of microscopy, culture and
      radiological investigations. At least two audit cycles were completed over 2
      years. Improvement was determined by comparing the performance between two six
      month periods pre- and post-intervention. Qualitative methods were used to
      ascertain facilitating and limiting contextual factors influencing change among
      healthcare professionals' clinical behaviour after the introduction of clinical
      audit. RESULTS: We found a significant improvement in 11 of 13 criteria in Cuba,
      in 2 of 6 criteria in Bolivia and in 2 of 5 criteria in Peru. Twelve out of 24 of
      the audit criteria in all three countries reached the agreed standards. Barriers
      to quality improvement included conflicting objectives for clinicians and TB
      programmes, poor coordination within the health system and patients' attitudes
      towards illness. CONCLUSIONS: Clinical audit may drive improvements in the
      quality of clinical care in resource-poor settings. It is likely to be more
      effective if integrated within and supported by the local TB programmes. We
      recommend developing and evaluating an integrated model of quality improvement
      including clinical audit.

PMID- 18318699
TI  - The prevalence of allergic diseases in an unselected group of 6-year-old
      children. The DARC birth cohort study.
AB  - This study determines the prevalence of atopic dermatitis, asthma,
      rhinoconjunctivitis, food hypersensitivity and urticaria and the frequency of
      sensitization in children with and without clinical allergic disease. In an
      ongoing prospective non-interventional birth cohort study of 562 unselected
      children, 404 children were subjected to interview, clinical examination, lung
      function measurements and allergy testing at 6 yr of age. Sensitization measured
      by skin prick test (SPT) and specific immunoglobulin E (S-IgE) was determined for
      24 different allergens. The 1-yr period prevalence of atopic dermatitis, asthma
      and rhinoconjunctivitis was 14.4%, 6.2% and 13.6%. 25.7% of the children suffered
      from at least one of the three diseases. The frequency of sensitization in
      children with no disease (controls), any allergic disease, atopic dermatitis,
      asthma and rhinoconjunctivitis was 17%, 45%, 47%, 56% and 55% (defined as SPT
      >or=3 mm and/or S-IgE >or=0.35 kU/l for at least one allergen). Symptoms were
      linked to sensitization for 44% in the asthma group and 42% in the
      rhinoconjunctivitis group, whereas sensitization could not be linked to worsening
      of the eczema in any cases of atopic dermatitis. Overlap between the three
      diseases was significantly more frequent in sensitized children than in non
      sensitized (19/46 = 41% vs. 9/58 = 16%, p = 0.004). The prevalence of food
      hypersensitivity and urticaria was 1.2% and 5.4% respectively. In unselected 6 yr
      old children, approximately half of the children with atopic dermatitis, asthma
      or rhinoconjunctivitis are IgE-sensitized. Sensitization tends to link these
      diseases to each other.

PMID- 18318700
TI  - Keratosis lichenoides chronica in an Indian child following erythroderma.
AB  - A 4-year-old boy presented with mildly itchy, linear, skin lesions over the
      trunk, arms, and face of 3 months' duration. He had previously been admitted to a
      private hospital for generalized exfoliation of the skin following drug intake
      for fever and throat pain. The nature of the drugs was not known. The exfoliative
      dermatitis was treated with oral prednisolone, 10 mg daily, tapered over 3 weeks.
      No further topical or oral medication was given. The present skin lesions started
      1 month after the cessation of the steroids. There was no family history of skin
      lesions, voice changes, or systemic complaints. Cutaneous examination showed
      multiple violaceous, linear, reticulate ridges with adherent scaling over the
      chest, back, and neck. There were scaly, flat-topped papules over the extensor
      aspects of both upper arms and the buttocks, and scaly plaques over the cheeks
      (Figs 1a-d and 2a,b). The scalp showed diffuse greasy scaling. There were no
      oral, genital, axillary, or eye lesions. The nails were normal. Systemic
      examination did not reveal any abnormal finding. Routine hematologic
      investigations, liver and kidney function tests, tests for hepatitis B and C, and
      enzyme-linked immunosorbent assay (ELISA) for HIV were normal. Histopathology
      from skin lesions on the back revealed hyperkeratosis, patchy parakeratosis,
      follicular plugging, alternating irregular acanthosis and epidermal thinning,
      basal cell degeneration, and a band-like inflammatory infiltrate of lymphocytes,
      histiocytes, and a few plasma cells (Fig. 3). Based on the classical clinical
      features and histopathology, keratosis lichenoides chronica was diagnosed, and
      topical 1% hydrocortisone acetate cream, twice daily, was prescribed. There was
      slight relief of pruritus at a follow-up visit after 3 weeks; however, the
      patient was subsequently lost to follow-up.

PMID- 18318701
TI  - A case of extragenital chancre on a nipple from a human bite during sexual
      intercourse.

PMID- 18318702
TI  - Difference in apolipoprotein E type 4 allele (APOE epsilon 4) among dentate and
      edentulous subjects.
AB  - OBJECTIVES: To evaluate the frequency of apolipoprotein (APOE) alleles and
      determine whether APOE type 4 allele (epsilon 4) was associated with
      edentulousness even when certain factors were controlled. BACKGROUND: The APOE
      are important in lipid homeostasis, and APOE epsilon 4 has been found in many
      diseases and to have a negative impact on longevity. Tooth loss is more common in
      ill aged subjects with low income and education. MATERIALS AND METHODS: In a
      population-based study involving 1860 subjects between 35 and 85 years 1321
      dentate (mean age = 54; 54% women, 46% men) and 539 edentulous (mean age = 72;
      62% women, 38% men) subjects were studied. Logistic regression was performed with
      dentate/edentulous as dependent variables and years of education, socio-economic
      status, social network, stress level, handicap from birth, 23 various diseases
      and APOE epsilon 4 as covariates. Thereafter, APOE epsilon 4 frequencies were
      studied in 342 dentate and 336 edentulous subjects 50-85 years of age. The
      subjects were matched with regard to age, gender, years of education, living
      condition, stress level, handicap from birth and 23 various diseases. RESULTS:
      APOE allele frequency in the total group was epsilon 2 = 7.8%, epsilon 3 = 76.4%
      and epsilon 4 = 15.8%. Age, living condition, years of education and APOE epsilon
      4 were significant covariates in edentulous subjects (p <or= 0.001). APOE epsilon
      4 in the matched groups revealed significant differences between the dentate
      group and the edentulous group (chi2 = 5.68; p = 0.017). There was no group
      effect (F(29,648) = 0.849; p < 0.696; Wilks' lambda = 0.963). In the dentate
      group, the frequencies of APOE were: epsilon 2 = 8.8%, epsilon 3 = 77.9% and
      epsilon 4 = 13.3%. Corresponding frequencies of APOE in the edentulous group
      were: epsilon 2 = 6.6%, epsilon 3 = 75.4% and epsilon 4 = 18.0%. CONCLUSION:
      Despite matching both groups with regard to different background factors, the
      edentulous group had a higher frequency of APOE epsilon 4 than the dentate group.
      Thus, genetic factors might contribute to greater risk in developing complex oral
      diseases leading to tooth loss or just be an indication that the subjects in our
      study carrying APOE epsilon 4 are more fragile.

PMID- 18318703
TI  - Melatonin receptor antagonist luzindole is a powerful radical scavenger in vitro.

PMID- 18318704
TI  - Age-related alterations in Ca2+ signals and mitochondrial membrane potential in
      exocrine cells are prevented by melatonin.
AB  - Information regarding age-induced Ca(2+) signal alterations in nonexcitable cells
      is limited. In addition, little evidence exists on the ability of melatonin to
      palliate the effects of aging on Ca(2+) signals and mitochondrial potential, a
      parameter involved in both Ca(2+) signaling and aging. We studied the ability of
      melatonin to prevent the effects of aging on intracellular Ca(2+) homeostasis and
      mitochondrial potential in exocrine cells. Pancreatic acinar cells were obtained
      from adult (3 months old) and aged (22-24 months old) mice by collagenase
      dispersion. Ca(2+) signals, in situ mitochondrial potential and in vitro amylase
      secretion were determined. Secretion in response to increasing levels of the
      secretagogues, acetylcholine and cholecystokinin (CCK), were impaired in aged
      pancreatic acini. This decrease was accompanied by an inhibition in the amplitude
      of the peak response to maximal concentrations of the agonists, and by a decrease
      in the pattern of Ca(2+) oscillations induced by postprandial levels of CCK. Both
      the size of the calcium pools, assessed by low levels of ionomycin, and
      capacitative calcium entry, induced by depletion of the stores with thapsigargin,
      were diminished in aged cells. These changes in Ca(2+) homeostasis were
      associated with depolarization of intracellular mitochondria. Oral administration
      of melatonin for 3 months to aged mice restored the secretory response, the
      amplitude and frequency of Ca(2+) responses, the size of intracellular calcium
      pools, the capacitative calcium entry, and the mitochondrial potential. In
      conclusion, melatonin restores secretory function, Ca(2+) signals and
      mitochondrial potential of aged exocrine cells.

PMID- 18318705
TI  - Chronotherapy beyond blood pressure reduction?

PMID- 18318706
TI  - An electromyographic evaluation of bilateral symmetry of masticatory, neck and
      trunk muscles activity in patients wearing a positioner.
AB  - This study was designed to investigate the attitude of a positioner (Finition) or
      an Hawley's retention appliance to create a symmetric function of the
      masticatory, neck and trunk muscles during the orthodontic retention phase.
      Sixteen patients (18.5 +/- 2.2 years) were included in the sample. All the
      patients received an orthodontic therapy for the treatment of an Angle's class I
      malocclusion and skeletal class I, for a period of 2 years. After removal of
      orthodontic brackets, eight patients wore a teeth positioner (group I) as
      retention appliance and eight subjects wore an Hawley's appliance as upper
      retention (group II). Surface electromyographic (sEMG) activity was recorded from
      the bilateral anterior temporal, posterior temporal, masseter,
      sternocleidomastoid (SCM), upper and lower trapezius and cervical muscles at
      mandibular rest position and during maximal voluntary clenching (MVC) at T0, i.e.
      soon after the removal of orthodontic brackets and at T1, i.e. after 3 months of
      retention treatment. No significant difference was observed between the two
      groups at T0. At T1, at mandibular rest position, the group I showed a
      significantly lower sEMG activity of anterior temporal and SCM muscles compared
      with the group II. During MVC, at T1, the group I showed a significantly lower
      sEMG activity of the SCM and posterior cervicals, compared with the group II. The
      positioner seems to show a relevant effect on the sEMG activity of masticatory,
      neck and trunk muscles.

PMID- 18318707
TI  - Dysfunction of CD4+CD25high T regulatory cells in patients with recurrent
      aphthous stomatitis.
AB  - BACKGROUND: Recurrent aphthous stomatitis (RAS) is a chronic inflammatory disease
      of unknown etiology characterized by recurring formation of painful oral ulcers.
      RAS may result from oral epithelium damage caused by T-cell-mediated immune
      response. CD4(+)CD25(+) T regulatory (Treg) cells suppress proliferation and
      effector functions of other immune cells, and therefore are crucial in regulating
      the immune response. METHODS: We tested the function of peripheral
      CD4(+)CD25(high) Treg cells in active RAS through their ability to inhibit
      proliferation and cytokine production of conventional CD4(+) T cells. We also
      attempted to detect the presence of FOXP3 and indoleamine 2,3-dioxygenase (IDO)
      mRNA in the lesional and non-lesional oral mucosa of RAS patients and healthy
      individuals using real-time PCR assay. RESULTS: Treg cells derived from RAS
      patients were less efficient in the suppression of cytokine production of CD4(+)
      T effector cells than Treg cells from healthy individuals. Moreover, in RAS, Treg
      cells were nearly twice less potent in the inhibition of CD4(+)CD25(-) T cell
      proliferation than in healthy donors. Furthermore, we have demonstrated the
      decreased proportion of CD4(+)CD25(+)FOXP3(+) Treg cells in peripheral blood of
      RAS patients compared with controls. We failed to detect FOXP3 mRNA, while IDO
      mRNA expression was decreased in non-lesional mucosa biopsies from RAS patients
      compared with ulcer biopsies or normal mucosa from healthy donors. CONCLUSIONS:
      These findings suggest that CD4(+)CD25(high) Treg cells are both functionally and
      quantitatively compromised in RAS and that decreased constitutive expression of
      IDO in oral mucosa in RAS may lead to the loss of local immune tolerance.

PMID- 18318708
TI  - The role of glutathione reductase in the interplay between oxidative stress
      response and turnover of cytosolic NADPH in Kluyveromyces lactis.
AB  - The phosphoglucose isomerase mutant of the respiratory yeast Kluyveromyces lactis
      (rag2) is forced to metabolize glucose through the oxidative pentose phosphate
      pathway and shows an increased respiratory chain activity and reactive oxygen
      species production. We have proved that the K. lactis rag2 mutant is more
      resistant to oxidative stress (OS) than the wild type, and higher activities of
      glutathione reductase (GLR) and catalase contribute to this phenotype. Resistance
      to OS of the rag2 mutant is reduced when the gene encoding GLR is deleted. The
      reduction is higher when, in addition, catalase activity is inhibited. In K.
      lactis, catalase activity is induced by peroxide-mediated OS but GLR is not. We
      have found that the increase of GLR activity is correlated with that of glucose-6
      phosphate dehydrogenase (G6PDH) activity that produces NADPH. G6PDH is positively
      regulated by an active respiratory chain and GLR plays a role in the reoxidation
      of the NADPH from the pentose phosphate pathway in these conditions. Cytosolic
      NADPH is also used by mitochondrial external alternative dehydrogenases. Neither
      GLR overexpression nor induction of the OS response restores growth on glucose of
      the rag2 mutant when the mitochondrial reoxidation of cytosolic NADPH is blocked.

PMID- 18318709
TI  - The inheritance of mtDNA in lager brewing strains.
AB  - In this work, we compared the mtDNA of a number of interspecific Saccharomyces
      hybrids (Saccharomyces cerevisiae x Saccharomyces uvarum and S. cerevisiae x
      Saccharomyces bayanus) to the mtDNA of 22 lager brewing strains that are thought
      to be the result of a natural hybridization between S. cerevisiae and another
      Saccharomyces yeast, possibly belonging to the species S. bayanus. We detected
      that in hybrids constructed in vitro, the mtDNA could be inherited from either
      parental strain. Conversely, in the lager strains tested, the mtDNA was never of
      the S. cerevisiae type. Moreover, the nucleotide sequence of lager brewing
      strains COXII gene was identical to S. bayanus strain NBRC 1948 COXII gene. MtDNA
      restriction analysis carried out with three enzymes confirmed this finding.
      However, restriction analysis with a fourth enzyme (AvaI) provided restriction
      patterns for lager strains that differed from those of S. bayanus strain NBRC
      1948. Our results raise the hypothesis that the human-driven selection carried
      out on existing lager yeasts has favored only those bearing optimal fermentation
      characteristics at low temperatures, which harbor the mtDNA of S. bayanus.

PMID- 18318710
TI  - In vivo proteome analysis of Xanthomonas campestris pv. campestris in the
      interaction with the host plant Brassica oleracea.
AB  - The genus Xanthomonas is composed of several species that cause severe crop
      losses around the world. In Latin America, one of the most relevant species is
      Xanthomonas campestris pv. campestris, which is responsible for black rot in
      cruciferous plants. This pathogen causes yield losses in several cultures,
      including cabbage, cauliflower and broccoli. Although the complete structural
      genome of X. campestris pv. campestris has been elucidated, little is known about
      the protein expression of this pathogen in close interaction with the host plant.
      Recently, a method for in vivo analysis of Xanthomonas axonopodis pv. citri was
      developed. In the present study, this technique was employed for the
      characterization of the protein expression of X. campestris pv. campestris in
      close interaction with the host plant Brassica oleracea. The bacterium was
      infiltrated into leaves of the susceptible cultivar and later recovered for
      proteome analysis. Recovered cells were used for protein extraction and separated
      by two-dimensional electrophoresis. Proteins were analysed by peptide mass
      fingerprinting or de novo sequencing and identified by searches in public
      databases. The approach used in this study may be extremely useful in further
      analyses in order to develop novel strategies to control this important plant
      pathogen.

PMID- 18318711
TI  - Ecophysiology and geochemistry of microbial arsenic oxidation within a high
      arsenic, circumneutral hot spring system of the Alvord Desert.
AB  - Microbial metabolism of arsenic has gained considerable interest, due to the
      potential of microorganisms to drive arsenic cycling and significantly influence
      the geochemistry of naturally arsenic-rich or anthropogenically arsenic-polluted
      environments. Alvord Hot Spring in southeastern Oregon is a circumneutral hot
      spring with an average arsenic concentration of 4.5 mg L(-1) (60 microM).
      Hydrogeochemical analyses indicated significant arsenite oxidation, increased pH
      and decreased temperature along the stream channels flowing into Alvord Hot
      Spring. The dynamic range of pH and temperature over the length of three stream
      channels were 6.76-7.06 and 69.5-78.2 degrees C, respectively. Biofilm samples
      showed As(III) oxidation ex situ. 16S rRNA gene studies of sparse upstream
      biofilm indicated a dominance of bacteria related to Sulfurihydrogenibium,
      Thermus, and Thermocrinis. The lush downstream biofilm community included these
      same three groups but was more diverse with sequences related to uncultured OP10
      bacterial phylum, uncultured Bacteroidetes, and an uncultured clade. Isolation of
      an arsenite oxidizer was conducted with artificial hot spring medium and yielded
      the isolate A03C, which is closely related to Thermus aquaticus based on 16S rRNA
      gene analysis. Thus, this study demonstrated the bacterial diversity along
      geochemical gradients of temperature, pH and As(III): As(V), and provided
      evidence of microbial arsenite oxidation within the Alvord Hot Spring system.

PMID- 18318712
TI  - Environmental Vibrio spp., isolated in Mozambique, contain a polymorphic group of
      integrative conjugative elements and class 1 integrons.
AB  - Circulation of mobile genetic elements linked to drug resistance spread was
      studied in Vibrio strains isolated from surface urban water (river and sea) and
      shellfish samples in 2002-2003 in Maputo, Mozambique. Class 1 integrons and
      integrating conjugative elements (ICE) were investigated by PCR and mating
      experiments in strains of major health interest: 10 Vibrio cholerae, six Vibrio
      parahaemolyticus, two Vibrio alginolyticus and one Vibrio fluvialis. Resistance
      to at least two antibiotics (predominantly beta-lactams) was detected in all the
      strains, with additional resistances to sulfamethoxazole, spectinomycin,
      streptomycin and/or trimethoprim. Class 1 integrons contributed partially to the
      expression of drug resistance and were found in five isolates: four V. cholerae
      (blaP1 cassette, one strain also contained the dfrA15 cassette) and one V.
      alginolyticus (aadA2 cassette). ICEs, apparently devoid of resistance genes, were
      found in eight V. cholerae, three V. parahaemolyticus and one V. fluvialis
      isolates. A wide variability was observed by molecular characterization of ICEs.
      Five ICEs were included in the SXT/R391 family and seven ICEs were not
      classified. Our results indicate that the SXT/R391 family and related ICEs
      comprise a large class of polymorphic genetic elements widely circulating in
      environmental Vibrio strains in Africa, beside those evidently linked to drug
      resistance in clinical isolates.

PMID- 18318713
TI  - Changes in Escherichia coli outer membrane subproteome under environmental
      conditions inducing the viable but nonculturable state.
AB  - Changes in the outer membrane subproteome of Escherichia coli along the
      transition to the viable but nonculturable state (VBNC) were studied. The VBNC
      state was triggered by exposure of E. coli cells to adverse conditions such as
      aquatic systems, starvation, suboptimal temperature, visible light irradiation
      and seawater. The subproteome, obtained according to Molloy et al., was analysed
      at the beginning of exposure (inoculum, phase 1), after a variable exposure time
      (95% of population culturable, phase 2) and when populations were mainly in the
      VBNC state (95% of cells VBNC, phase 3). Proteome changes were dependent on
      adverse conditions inducing the transition and were detected mainly in phase 2.
      The permanence of E. coli cells in seawater under illumination conditions
      entailed a dramatic rearrangement of the outer membrane subproteome involving 106
      new spots, some of which could be identified by peptide fingerprinting. However,
      proteins exclusive to the VBNC state were not detected.

PMID- 18318714
TI  - Quantification of mcrA by fluorescent PCR in methanogenic and methanotrophic
      microbial communities.
AB  - A quantitative fluorogenic PCR method for detecting methanogenic and
      methanotrophic orders was established using a refined primer set for the methyl
      coenzyme M reductase subunit A gene (mcrA). The method developed was applied to
      several microbial communities in which diversity and abundance of methanogens or
      anaerobic methanotrophs (ANMEs) was identified by 16S rRNA gene clone analysis,
      and strong correlations between the copy numbers of mcrA with those of archaeal
      16S rRNA genes in the communities were observed. The assay can be applied to
      detecting and assessing the abundance of methanogens and/or ANMEs in anoxic
      environments that could not be detected by 16S rRNA gene sequence analyses.

PMID- 18318715
TI  - Consumption of functional fermented milk containing borage oil, green tea and
      vitamin E enhances skin barrier function.
AB  - As emerging studies show that skin functioning can be improved with orally
      imbibed ingredients, we decided to investigate a mixture of borage oil,
      catechins, vitamin E and probiotics, all known for their reported effects on
      epidermal function, in a fermented dairy product, for the first time. Gamma
      linolenic acid (GLA) and catechins bioavailability and their effects on skin
      functionality have not been previously investigated from a fermented dairy
      product. Firstly, we assessed the bioavailability of GLA and catechins mixed in a
      fermented dairy matrix by measuring their levels in chylomicrons and plasma
      samples respectively. For the GLA contained in the dairy matrix, the area under
      the curve and time for maximal absorption were significantly different to the
      same kinetic parameters compared with absorption from the free oil indicating
      improved oral bioavailability. However, the overall absorption of catechins over
      the 6-h period was identical for both product forms. These results were
      sufficiently promising to warrant a 24 week skin nutrition intervention study in
      female volunteers having dry and sensitive skin. The product improved stratum
      corneum barrier function compared with a control product as early as 6 weeks
      after the consumption which continued throughout the rest of the study. The
      reduction in transepidermal water loss relative to control was maintained
      throughout the trial despite seasonal changes. Moreover, as a result of the
      enhanced bioavailability, a much greater effect on skin barrier function occurred
      than reported previously for the individual ingredients. Nevertheless, body mass
      index significantly influenced various outcome measurements of this study.

PMID- 18318716
TI  - Novel uncultured Chloroflexi dechlorinate perchloroethene to trans-dichloroethene
      in tidal flat sediments.
AB  - The marine environment represents a rich source of bio- and geogenically produced
      organohalogens, including the common pollutant perchloroethene (PCE). However,
      diversity and function of marine chloroethene-dechlorinating microorganisms are
      largely unknown. Here, we have studied the activity and composition of a tidal
      flat sediment bacterial and archaeal community from the North Sea exposed to low
      concentrations of PCE. After 2 weeks of incubation, PCE was rapidly dechlorinated
      via trichloroethene to dichloroethene (DCE). Unexpectedly, these microcosms
      produced 3.5-fold more trans-DCE than cis-DCE. The actively dechlorinating
      microbial populations were traced by stable isotope probing of rRNA with (13)C
      labelled acetate for 4 days. Terminal restriction fragment length polymorphism
      fingerprinting and clone libraries of isotopically enriched, 'heavy'(13)C
      labelled bacterial 16S rRNA revealed the populations potentially involved in
      reductive dechlorination. Major clone groups belonged to the Proteobacteria
      (50.0%; 22.4% delta-, 12.1% gamma-, 6.9% alpha-, 6.9% beta- and 1.7% epsilon
      subgroup) and Chloroflexi (29.3%). Populations represented by the two dominant
      terminal restriction fragments were affiliated with the Dehalococcoidetes
      (subphylum II of the Chloroflexi), and were exclusively detected in the heavy
      fraction of the PCE-dechlorinating incubation. The phylogenetically novel, larger
      population, designated Tidal Flat Chloroflexi Cluster, was closely related to the
      recently discovered PCE-dechlorinating Lahn Cluster bacteria from anoxic river
      sediment but more distantly related to canonical Dehalococcoides spp. (92-94%
      sequence identity). The second population was closely related to 'Dehalobium
      chlorocoercia DF-1'. Both populations appear to be responsible for reductive
      dechlorination of highly chlorinated ethenes to predominantly trans-DCE in tidal
      flat sediment incubations.

PMID- 18318717
TI  - Global concordance in diversity patterns of vascular plants and terrestrial
      vertebrates.
AB  - The factors that determine large-scale patterns of species richness are poorly
      understood. In particular, biologists have not determined the relative roles of
      taxon-specific characteristics that influence diversification and distribution,
      and region-specific features that promote and constrain diversity. We show that
      the numbers of species of vascular plants and of four terrestrial vertebrate taxa
      (mammals, birds, reptiles and amphibians) vary in parallel across 296 geographic
      areas covering most of the globe, even after accounting for sample area, climate,
      topographic heterogeneity and differences between continents. Thus, a common set
      of regional characteristics and processes appears to shape patterns of species
      richness in a diverse set of taxa, despite substantial differences in their
      biological traits.

PMID- 18318718
TI  - Spatial mating networks in insect-pollinated plants.
AB  - Gene flow in plant populations is largely determined by landscape heterogeneity.
      Both the shape of the pollination kernel and the spatial distribution of trees
      affect the distribution of pollen grains and the genotypes they harbour, but
      little is known about the relative contribution of each of these two factors.
      Using genetic markers we build a spatial network of pollination events between
      any two trees in a population of Prunus mahaleb, an insect-pollinated plant.
      Then, we apply tools from the science of complex networks to characterize the
      structure of such a mating network. Although the distribution of the number of
      pollen donors per tree is quite homogeneous, the identity of donors is
      distributed heterogeneously across the population. This results in a population
      structured in well-defined modules or compartments, formed by a group of mother
      trees and their shared pollen donors. Long-distance pollination events decrease
      the modular structure by favouring mating among all available mates. This
      increases gene flow across the entire population, reducing its genetic structure,
      and potentially decreasing the role of genetic drift.

PMID- 18318719
TI  - Effect of aspirin and heparin on random skin flap survival in rats.
AB  - BACKGROUND: Aspirin and heparin are commonly given to patients undergoing
      microvascular procedures to increase flap survival and patency, yet there is
      scant information concerning the effect these flaps have on nonmicrovascular
      flaps. OBJECTIVE: The objective was to obtain baseline values concerning the
      effect of aspirin and heparin on the viability of standardized flap tissues.
      METHODS AND MATERIALS: One hundred rats were divided into five groups receiving
      high-dose aspirin, low-dose aspirin, high-dose aspirin in combination with
      heparin, and heparin alone and the final group were controls. The viability of
      the tissue was measured at 1 week by fluorescein fluorescence. RESULTS: There was
      significant improvement in flap survival in the high-dose aspirin and high-dose
      aspirin combination groups. CONCLUSIONS: It appears that high-dose aspirin
      increases survival of ischemic flap tissue irrespective of the presence of
      microvascular anastomosis and may be of clinical benefit in all flap surgery. The
      authors have indicated no significant interest with commercial supporters.

PMID- 18318720
TI  - Treatment of dermatofibroma sarcoma protuberans using modified Mohs micrographic
      surgery: no recurrences and smaller defects.
AB  - OBJECTIVES: The purpose of this study was to evaluate the use of modified Mohs
      micrographic surgery (MMS) for dermatofibroma sarcoma protuberans (DFSP) in a
      single institution by a single surgeon. METHODS: The authors conducted a
      retrospective analysis of 25 patients with DFSP who were treated with modified
      MMS over the past 19 years at Scripps Clinic. RESULTS: Of the 25 patients treated
      with modified MMS for DFSP, there were no identifiable recurrences. The mean
      follow-up time was 101 months. The defect sizes of DFSP lesions treated by
      modified MMS are smaller than if the lesions had been treated with the standard
      wide local excision (WLE) margins of 3 cm. LIMITATIONS: This is a retrospective
      analysis using the data of one surgeon. Five of the 25 patients were not examined
      in our office. Not all patients had 5-year follow-up. There were no cases of the
      fibrosarcomatous variant. CONCLUSION: Our data support the growing literature
      that modified MMS achieves excellent local control for DFSP with a possible
      benefit of smaller defects when compared with treatment with WLE. The authors
      have indicated no significant interest with commercial supporters.

PMID- 18318721
TI  - Split-face comparison of the erbium micropeel with intense pulsed light.
AB  - BACKGROUND: A variety of photorejuvenative techniques have been utilized to
      reverse the signs of cutaneous photoaging, including ablative and nonablative
      laser resurfacing as well as light-based devices. OBJECTIVE: The purpose of this
      split-face randomized prospective open-label trial was to determine the
      effectiveness of sequential erbium:yttrium-aluminum-garnet (Er:YAG) laser versus
      intense pulsed light (IPL) for the treatment of mild to moderate facial
      photodamage. MATERIALS AND METHODS: Ten subjects (ages 35-63) with facial
      dyschromia and rhytides were enrolled. Study patients were randomized to the two
      treatment arms, Er:YAG (3.8 J/cm(2), 30% pattern overlap, 0% interpulse overlap,
      15 microm per pass with no coagulation) and IPL (560-nm filter, 30 J/cm(2),
      2.4/4.0-ms pulse with 10-ms delay), each receiving three sequential treatments
      spaced 1 month apart. Subjective and blinded physician evaluations were performed
      at baseline and 4, 8, and 20 weeks posttreatment using a nominal scale from 1 to
      4. Erythema and adverse events were assessed 1 week following each treatment.
      RESULTS: Ten female subjects with mild to moderate facial photodamage were
      treated with one pass of either IPL or Er:YAG in a split-face fashion. Patients
      received three treatments each spaced 1 month apart. Nine of 10 patients
      completed the trial; 1 withdrew due to pain during the second Er:YAG treatment.
      Baseline subjective and blinded physician dyschromia and rhytid scores revealed
      no significant difference between the IPL and Er:YAG randomly assigned sides. Up
      to three IPL or Er:YAG treatments did not result in a significant improvement in
      rhytid scores. Subjective and blinded physician dyschromia scores improved 26 and
      38%, respectively, 3 months after the final IPL treatment, but only by 7 and 29%,
      respectively, with Er:YAG. Subjective global facial appearance scores worsened by
      5% while blinded physician scores improved by 16% 3 months after 3 Er:YAG
      treatments, but by 28 and 20% for IPL, respectively. The overall incidence of
      adverse events and subsequent downtime was increased for Er:YAG (1/10 patients
      experienced hyperpigmentation, 3/10 exfoliation, 1/10 blistering, and 5/10
      discomfort) compared to IPL (1/10 exfoliation and 1/10 discomfort), although no
      permanent side effects were observed with either treatment arm. CONCLUSIONS:
      While low-fluence erbium resurfacing has a modest effect on facial photodamage,
      patients preferred IPL because it resulted in less downtime. The authors have
      indicated no significant interest with commercial supporters.

PMID- 18318722
TI  - Subdermal Nd-YAG laser for axillary hyperhidrosis.
AB  - BACKGROUND: Axillary hyperhidrosis is a common but difficult-to-treat condition
      with major social, labor, and emotional consequences. OBJECTIVE: The aim of this
      study is to present the Nd-YAG laser as a safe and effective option for the
      treatment of axillary hyperhidrosis. MATERIALS AND METHODS: From January 2002 to
      April 2007, 17 patients (15 women and 2 men) with axillary hyperhidrosis were
      treated using a subdermal 1,064-nm Nd-YAG laser. The results were evaluated by
      the patients as well as by the physician. The objective evaluation was realized
      by Minor's iodine starch test combined with planimetry. Histology was performed
      in axillary skin after the laser treatment. RESULTS: The subdermal laser-assisted
      axillary hyperhidrosis treatment using a 1,064-nm Nd-YAG laser resulted in
      significant clinical improvement. CONCLUSIONS: The treatment of axillary
      hyperhidrosis using the 1,064-nm Nd-YAG laser has the advantage of a minor
      invasive procedure without leaving large scars and causing temporary impairment.
      The laser proved to be effective and safe. Although the laser treatment has shown
      promising results in this pilot trial, further studies are necessary for final
      conclusions. The authors have indicated no significant interest with commercial
      supporters.

PMID- 18318723
TI  - Efficacy of botulinum toxin type A in the treatment of focal axillary
      hyperhidrosis.
AB  - BACKGROUND: Local intradermal injection of botulinum toxin Type A has become a
      recognized treatment for axillary hyperhidrosis. This study has investigated the
      efficacy of this method of treatment in terms of symptom-free interval between
      treatments and patients' satisfaction. We also investigated the reliance on
      patients' subjective assessment of the recurrence of symptoms in determining the
      timing of repeat injections. METHODS: All patients referred to our clinic between
      May 2001 and December 2005 with a diagnosis of focal primary axillary
      hyperhidrosis were included in this study. Data were collected prospectively in a
      standard proforma. Every patient received a questionnaire to complete over a 4
      week period. The questionnaire included visual analogue scales for periprocedural
      pain, degree of dryness, satisfaction, regret, and complications. Final symptom
      free interval was recorded when the patient requested a repeat injection. The
      data were recorded on a spreadsheet and analyzed using standard statistical
      methods. RESULTS: A total of 52 consecutive patients and 238 axillary injections
      were analyzed. The symptom-free interval ranged from 3 to 14 months with a median
      of 5.97 months. There were no significant complications from this treatment
      modality. A total of 97% of the patients were highly satisfied with only 1
      patient regretting the treatment. CONCLUSION: Botulinum toxin Type A is an
      effective and well-tolerated treatment for axillary hyperhidrosis. Timing of
      repeat injections as determined subjectively by patients is comparable to studies
      using colorimetric and gravimetric techniques to quantify the severity of
      sweating prior to the administration of repeat injections. The authors have
      indicated no significant interest with commercial supporters.

PMID- 18318724
TI  - Hydrogen peroxide and wound healing: a theoretical and practical review for hair
      transplant surgeons.
AB  - BACKGROUND: In most hair restoration practices, hydrogen peroxide has been
      routinely used to remove blood during and after hair transplant surgery. In other
      specialties, hydrogen peroxide is also used in these ways: wound cleaning,
      prevention of infection, hemostasis, and removal of debris. Despite its
      widespread use, there are still concerns and controversy about the potential
      toxic effect of hydrogen peroxide. OBJECTIVE: The objective was to review all
      available literature including in vivo and in vitro effects of hydrogen peroxide,
      as well as general wound healing research. MATERIAL AND METHODS: Literature up to
      and including the past three decades was investigated. RESULTS: Two pilot studies
      were found, and there are not enough data examining the real impact of using
      hydrogen peroxide in hair transplant surgery. In other specialties, H(2)O(2)
      appears to have positive effects, such as stimulation of vascular endothelial
      growth factor, induction of fibroblast proliferation, and collagen, or negative
      effects, such as cytotoxicity, inhibition of keratinocyte migration, disruption
      of scarless fetal wound repair, and apoptosis. CONCLUSIONS: There are not enough
      data in hair restoration surgery about the use of hydrogen peroxide, and it is
      unknown and unclear what the optimum dilution should be. Positive and negative
      effects were found in other specialties. Further studies are recommended. The
      authors have indicated no significant interest with commercial supporters.

PMID- 18318725
TI  - Expanded polytetrafluoroethylene implants for soft-tissue augmentation: 5-year
      follow-up and literature review.
AB  - BACKGROUND: Expanded polytetrafluoroethylene implants have been used successfully
      for augmentation of thinning lips, deep nasolabial folds, and marionette lines
      without the risk, recovery time, and expense of major surgery. OBJECTIVE: The
      objective was to assess long-term results and patient satisfaction with expanded
      polytetrafluoroethylene implants. MATERIALS AND METHODS: A retrospective chart
      review was performed on all patients treated with expanded
      polytetrafluoroethylene implants from January 1, 2001, to July 1, 2002. RESULTS:
      Eighty-five implants were placed in 33 patients. Forty-six percent of implants
      were placed in the nasolabial folds, 34% in the lips, 16.5% in the marionette
      lines, 2% in the oral commisures, and 1% in the glabella. Eighty-seven percent of
      implants remain in place with excellent correction. Eleven implants in 6 patients
      were removed. Four of the 11 implants removed were considered too small by the
      patient and were replaced with larger implants without difficulty. The other
      reasons for implant removal included malposition, localized swelling, and an
      unnatural feel. Patient and physician satisfaction with the treatment was high.
      CONCLUSION: Expanded polytetrafluoroethylene implants are a safe, effective, and
      permanent option for facial volume augmentation. Patients who have had their
      implants in place for 5 years or more continue to report high satisfaction with
      the treatment. The authors have indicated no significant interest with commercial
      supporters.

PMID- 18318726
TI  - Successful treatment with injected hyaluronic acid in a patient with lip
      asymmetry after surgical correction of cleft lip.
AB  - BACKGROUND: Surgical repair of cleft lip, while correcting deformity and
      dysfunction, may leave residual cosmetic imperfections. The resultant asymmetry
      and low volume of the upper lip can be addressed surgically and via less invasive
      methods. OBJECTIVE: We present the first reported use of injectable hyaluronic
      acid to correct the characteristic lip asymmetry and poor volume after surgical
      repair of a cleft lip. METHODS AND MATERIALS: Using injectable hyaluronic acid,
      we treated the patient's upper lip to restore symmetry and achieve an augmented
      volume. RESULTS: We obtained a symmetric correction and aesthetically pleasing
      volume augmentation in the affected lip. These results lasted approximately 4
      months. CONCLUSION: Using a temporary, alloplastic, injectable soft tissue filler
      such as hyaluronic acid satisfactorily achieves correction of asymmetry and low
      volume in a surgically repaired cleft lip. For patients who have endured multiple
      corrective surgeries, this is a novel and less invasive way to improve their
      cosmetic concerns.

PMID- 18318727
TI  - Tumescent suction curettage versus minimal skin resection with subcutaneous
      curettage of sweat glands in axillary hyperhidrosis.
AB  - BACKGROUND: Axillary hyperhidrosis is a common problem with a strong negative
      impact on professional and social life. Various types of surgical procedures have
      been developed for its treatment. OBJECTIVE: We want to compare efficacy and risk
      benefit ratio of two local surgical procedures, i.e., the minimal skin excision
      with subcutaneous curettage (Method A) and tumescent liposuction curettage
      (Method B). METHODS: A total of 163 patients with primary axillary hyperhidrosis
      as assessed by positive iodine-starch test were included. The age range of
      patients was 16 to 61 years (mean 28 years), including 33 males and 129 females.
      A total of 125 underwent Method A, and 37 were treated by Method B. Both
      procedures were performed in tumescent anesthesia. The mean follow-up was 21
      months (Method A) and 48 months (Method B). The outcome was evaluated by
      patient's global assessment and by Minor's starch test. Patient satisfaction was
      scored as "satisfied,""partially satisfied," or "dissatisfied." Adverse effects,
      complications, hospitalization time, and time to return to work were recorded and
      compared for both methods. In patients who underwent Method A, scar formation was
      assessed only for the first axilla (n=99). RESULTS: In Method A, the rate of
      residual sweating was 12.0%. The relapse rate was 1.0% of patients or 2% of
      axillae. In Method B, the relapse rate was 16.2% of patients or 14.5% of axillae
      within 12 months. If we consider both the relapses and the residual sweating,
      this modified relapse rate per axilla was 12.8% for Method A and 14.5% for Method
      B. Patients who underwent Method B had significantly less pain, no atrophic or
      hypertrophic scars, and no complications such as wound infections, bleeding (with
      the need of a second operation), or delayed healing. Using Method A, the stay in
      hospital was on average 5.8 days per patient or 3.2 days per axilla. Mean time to
      return to work was 8.8+/-3.5 days. For Method B, the procedure was performed in
      an outpatient setting. The mean time to return to professional work was 1.3+/-0.8
      days. The total satisfaction rate was 97% for Method A and 89.2% for Method B,
      respectively. CONCLUSIONS: As shown by this study, minor skin resection with
      subcutaneous curettage of axillary sweat glands (Method A) is somewhat more
      effective in permanent reduction of hyperhidrosis than suction curettage. The
      minimal invasiveness of suction curettage and the minimal scarring, however, are
      significant advantages over excisional surgery. Downtime after surgery is
      significantly shorter for suction curettage. Therefore, suction curettage might
      be the surgical treatment of choice for axillary hyperhidrosis.

PMID- 18318728
TI  - Treatment of facial telangiectasia using a dual-wavelength laser system (595 and
      1,064 nm): a randomized controlled trial with blinded response evaluation.
AB  - BACKGROUND AND OBJECTIVE: Pulsed dye (PDL) 595- and 1,064-nm Nd:YAG lasers are
      used for the treatment of vascular lesions. PDL-heated blood exhibits increased
      absorption of radiation at 1,064 nm, suggesting that the use of combined
      sequential dual wavelengths may offer benefits over single-wavelength treatments.
      This study compares the treatment efficacy of combined sequential dual-wavelength
      versus single delivery of 595-nm PDL or 1,064-nm Nd:YAG wavelengths in facial
      telangiectasia in a split face study design using subpurpuric parameters.
      MATERIALS AND METHODS: Twenty patients were studied using the sequential delivery
      of PDL and Nd:YAG wavelengths on one side of the nose. The other side received
      either PDL or Nd:YAG treatment. Vessels (<0.6 mm in diameter) were treated with a
      7-mm spot size at 10 J/cm(2), 10 ms with the PDL, followed by the Nd:YAG at 70
      J/cm(2), 15 ms with a multiplex interpulse delay of 100 ms. Subjects received a
      single treatment, and results were evaluated after 4-week follow-up. Improvement
      was determined by blinded assessment of photographs taken before and after final
      evaluation. RESULTS: The efficacy of the dual-wavelength laser treatment when
      compared to Nd:YAG or PDL laser alone was significantly more evident than either
      single-wavelength treatment (p<.05). There was no statistically significant
      difference in efficacy between the single-wavelength treatment groups.
      CONCLUSION: The sequential delivery of 595- and 1,064-nm-wavelength radiation
      with an interpulse delay suggests that the synergistic approach to laser therapy
      for facial telangiectasia is a superior method compared to standard single
      wavelength therapy.

PMID- 18318729
TI  - Efficacy and safety of intense pulsed light in treatment of melasma in Chinese
      patients.
AB  - BACKGROUND: Melasma is commonly seen in the Asian population. Traditional
      therapies are less effective and may cause adverse effects. OBJECTIVE: The
      objective was to study the efficacy and safety of a new intense pulsed light
      (IPL) device in the treatment of melasma in Chinese patients. METHODS: Eighty
      nine women with melasma were enrolled in this open-labeled study. Subjects
      received a total of four IPL treatments at 3-week intervals. Changes in facial
      hyperpigmentation and telangiectasis were evaluated using an objective, skin
      colorimeter (Mexameter, Courage & Khazaka), the melasma area and severity index
      (MASI), and a global evaluation by the patients and blind investigators. RESULTS:
      Sixty-nine of 89 patients (77.5%) obtained 51% to 100% improvement, according to
      the overall evaluation by dermatologists. Self-assessment by the patients
      indicated that 63 of 89 patients (70.8) considered more than 50% or more
      improvement. Mean MASI scores decreased substantially from 15.2 to 4.5. Mexameter
      results demonstrated a significant decrease in the degree of pigmentation and
      erythema beneath the melasma lesions. Patients with the epidermal-type melasma
      responded better to treatment than the mixed type. Adverse actions were minimal.
      CONCLUSION: IPL treatment is a good option for patients with melasma. Adverse
      actions of IPL were minimal and acceptable.

PMID- 18318730
TI  - Minimally ablative erbium:YAG laser resurfacing of facial atrophic acne scars in
      Asian skin: a pilot study.
AB  - BACKGROUND: Atrophic scars are dermal depressions caused by collagen damage most
      commonly occurring after inflammatory acne vulgaris. There are little published
      data regarding the effectiveness and safety of minimally invasive lasers in the
      treatment of atrophic acne scars in darker skin types. OBJECTIVE: The purpose was
      to evaluate the efficacy and safety of a low-fluence 2,940-nm erbium:YAG laser in
      the treatment of atrophic acne scars in Asian patients. MATERIALS AND METHODS:
      Nine patients aged 19 to 45 years with mild to moderate atrophic facial scars and
      Skin Types IV and V were treated with topical anesthesia and one to two passes
      with an erbium:YAG laser two times at 1-month intervals. Treatment parameters
      were 6-mm spot size, fluence of 400 mJ, pulse duration of 300 micros, and
      repetition rate of 2 Hz. RESULTS: At 2 months after the last treatment, mild to
      moderate clinical improvement was noted in all patients compared to baseline.
      Treatment was well tolerated. Side effects consisted of posttreatment erythema,
      peeling, and crusting, which resolved within 1 to 2 weeks. There was no
      postinflammatory hyper- or hypopigmentation, blistering, or hypertrophic
      scarring. CONCLUSION: Low-fluence erbium:YAG facial resurfacing was effective and
      safe in patients with mild to moderately severe atrophic acne scarring.

PMID- 18318731
TI  - Split-face treatment of facial dyschromia: pulsed dye laser with a compression
      handpiece versus intense pulsed light.
AB  - BACKGROUND: Many visible light lasers and intense pulsed light (IPL) devices are
      available to treat photodamaged skin. OBJECTIVES: The objective was to perform a
      multiple-treatment split-face comparison evaluating a pulsed dye laser (PDL) with
      a compression handpiece versus IPL for photorejuvenation. METHODS: Ten subjects
      were treated three times at 3- to 4-week intervals. One side of the face was
      treated with the PDL with compression handpiece, and the other with IPL. One
      month after final treatment, blinded evaluation assessed for improvements in
      dyschromias and texture. Patients provided self-assessment of improvement in
      dyschromias and texture. Time to complete final treatments and pain during all
      treatments were recorded for each device. RESULTS: Improvement of the PDL was
      (mean) 86.5, 65, 85, 38, and 40% for dark lentigines, light lentigines, vessels
      <0.6 mm, vessels >0.6 mm, and texture, respectively, versus 82, 62.5, 78.5, 32.5,
      and 32%, respectively, for the IPL side. Patient-evaluated difference in
      improvement for vascular lesions significantly favored the PDL (p=.011). Mean
      third treatment times were 7.7 minutes for PDL versus 4.6 minutes for the IPL
      (p=.005). Mean pain ratings were 5.8 for the PDL and 3.1 for the IPL (p=.007).
      Purpura-free procedures depended on proper technical use of the compression
      handpiece when treating lentigines with the PDL. CONCLUSIONS: The PDL with
      compression handpiece and IPL are highly effective for photorejuvenation.

PMID- 18318732
TI  - Development of the Gross Motor Function Classification System for cerebral palsy.
AB  - The Gross Motor Function Classification System (GMFCS) for cerebral palsy has
      been widely used internationally for clinical, research, and administrative
      purposes. This paper recounts the ideas and work behind the creation of the
      GMFCS, reports on the lessons learned, and identifies some philosophical
      challenges inherent in trying to develop an ordered, valid, and consistent system
      to describe function in children and adolescents with developmental differences.
      It is hoped that these ideas will be useful to others who choose to expand the
      field with additional systems in other areas of childhood neurodisability.

PMID- 18318733
TI  - VegT, eFGF and Xbra cause overall posteriorization while Xwnt8 causes eye-level
      restricted posteriorization in synergy with chordin in early Xenopus development.
AB  - We examined several candidate posterior/mesodermal inducing molecules using
      permanent blastula-type embryos (PBEs) as an assay system. Candidate molecules
      were injected individually or in combination with the organizer factor chordin
      mRNA. Injection of chordin alone resulted in a white hemispherical neural tissue
      surrounded by a large circular cement gland, together with anterior neural gene
      expression and thus the development of the anterior-most parts of the embryo,
      without mesodermal tissues. When VegT, eFGF or Xbra mRNAs were injected into a
      different blastomere of the chordin-injected PBEs, the embryos elongated and
      formed eye, muscle and pigment cells, and expressed mesodermal and posterior
      neural genes. These embryos formed the full spectrum of the anteroposterior
      embryonic axis. In contrast, injection of CSKA-Xwnt8 DNA into PBEs injected with
      chordin resulted in eye formation and expression of En2, a midbrain/hindbrain
      marker, and Xnot, a notochord marker, but neither elongation, muscle formation
      nor more posterior gene expression. Injection of chordin and posteriorizing
      molecules into the same cell did not result in elongation of the embryo. Thus, by
      using PBEs as the host test system we show that (i) overall anteroposterior
      neural development, mesoderm (muscle) formation, together with embryo elongation
      can occur through the synergistic effect(s) of the organizer molecule chordin,
      and each of the 'verall posteriorizing molecules'eFGF, VegT and Xbra; (ii) Xwnt8
      mediated posteriorization is restricted to the eye level and is independent of
      mesoderm formation; and (iii) proper anteroposterior patterning requires a
      separation of the dorsalizing and posteriorizing gene expression domains.

PMID- 18318734
TI  - Attitude to nephrolithiasis in the potential living kidney donor: a survey of the
      German kidney transplant centers and review of the literature.
AB  - Living donor kidney transplantation (LD-KTX) is increasing worldwide. With the
      prevalence of urolithiasis ranging between 4% and 15%, the number of donors with
      current nephrolithiasis or a history of the disease will increase as well. A
      questionnaire was sent to all German centers with LD-KTX programs (urologists and
      general surgeons). Answers were compared for differences between urological and
      surgical kidney transplant centers. Response rate was 74%. Nephrolithiasis at the
      time of KTX is an exclusion criterion at 36% of the German centers (58%
      urological/19% surgical, chi(2) = 4.65, p = 0.03, Fishers exact p = 0.05), 96% of
      the centers accept kidney donors with a history of nephrolithiasis. The length of
      the stone-free episode is regarded as relevant by 42% of all centers (58%
      urological vs. 32% surgical centers, p = ns). Stone composition is a criterion
      for 54% of centers (66% vs. 44%, p = ns). More than half of the centers accept a
      history of cystine stones, almost all centers of struvite and urate stones.
      Donors with current nephrolithiasis were less commonly accepted by urologists
      than by general surgeons. For almost all centers history of nephrolithiasis does
      not preclude living kidney donation. Stone composition proved to be of little
      relevance for decision making.

PMID- 18318735
TI  - Optimal interventional treatment and long-term outcomes for biliary stricture
      after liver transplantation.
AB  - We undertook an evaluation of the clinical outcomes of endoscopic cholangioplasty
      (ECP) and percutaneous cholangioplasty (PCP) for biliary strictures after liver
      transplantation. We compared success rates of intervention, patency after
      successful intervention and procedure-related morbidities in 79 patients with
      anastomotic stricture (n = 54) or non-anastomotic stricture (n = 25). Twenty-five
      ECP and 61 PCP procedures were performed; seven PCP procedures were consecutively
      performed after failure of ECP. Fifty-one (64.6%) patients were successfully
      treated by cholangioplasty. Successful intervention rates (60.0% in ECP vs. 59.3%
      in PCP, p = 1.00) and patencies after successful intervention (44.8 +/- 7.4
      months in ECP vs. 41.9 +/- 3.4 months in PCP, p = 0.47) were no different for the
      two techniques. However, the number of intervention sessions for PCP (7.2 +/-
      0.6) was higher than for ECP (2.9 +/- 0.6) (p < 0.01). Multivariate analysis
      showed that only an anastomotic stricture was found to be related with a longer
      patency with an estimated odds ratio of 5.74 (p = 0.04) and had a tendency to be
      associated with successful intervention with an estimated odds ratio of 3.12 (p =
      0.07) irrespective of techniques. Endoscopic access should be the preferred first
      approach in patients with biliary stricture after liver transplantation
      irrespective of the type of stricture, in view of its less invasive nature and
      patient convenience.

PMID- 18318736
TI  - Validation of the HCC-MELD for dropout probability in patients with small
      hepatocellular carcinoma undergoing locoregional therapy.
AB  - BACKGROUND: The model for end-stage liver disease (MELD) is used in prioritizing
      cirrhotic patients awaiting liver transplantation. Patients with small
      hepatocellular carcinoma (HCC) are eligible candidates. An HCC-MELD equation was
      recently proposed to predict the dropout rate of HCC patients on the waiting
      list. This study aimed to validate the accuracy of this equation. METHODS: We
      investigated 390 patients with small HCC who were candidates for liver
      transplantation and underwent locoregional therapy. RESULTS: The estimated
      probability of dropout according to the equation was 8.2% for T1 stage and 13.5%
      for T2 stage HCC (p < 0.0001). The actual disease progression rate at three
      months was 2.1% for T1 and 3.0% for T2 stage HCC. At six months, the progression
      rate was 5.3% for T1 stage and 6.8% for T2 stage. The area under receiver
      operating characteristic curve of the HCC-MELD equation was 0.81 at three months
      and 0.80 at six months. Patients undergoing radiofrequency ablation (RFA) had
      significantly lower dropout rates compared with other treatment groups according
      to the equation (p = 0.0007). The actual tumor progression rate was also the
      lowest for the RFA group at both three and six months. CONCLUSION: The HCC-MELD
      equation is a feasible predictive model for patients with small HCC undergoing
      locoregional therapy.

PMID- 18318737
TI  - Determinants of bone mass in end-stage renal failure patients at the time of
      kidney transplantation.
AB  - BACKGROUND: Patients with chronic renal failure (CRF) are at high risk of renal
      osteodystrophy. Our study aimed to identify predictors of bone mass and
      cumulative fracture rate at the time of renal transplantation (RTx). This is
      important since the patients experience further substantial bone loss the first
      month post-transplant. MATERIAL AND METHODS: Altogether 133 renal transplant
      patients were examined for bone mineral density (BMD) using dual-energy X-ray
      absorptiometry shortly after RTx. RESULTS: The patients'Z-scores were
      significantly lower at the time of RTx compared to the reference population (p <
      0.05), 32% were osteopenic and 11% had osteoporosis. Independent predictors of
      low bone mass were age (p < 0.001), female sex (p < 0.001), intact parathyroid
      hormone (iPTH) level (p < 0.001), former transplantation (p = 0.001) and time on
      hemodialysis (HD) (p = 0.005). Body mass index (BMI) (p < 0.001) and physical
      activity (p = 0.027) were associated with high BMD. Cumulative fracture rate
      (29%) was associated with physical inactivity (p = 0.003), BMI (p = 0.036) and
      osteopenia (p < 0.001) at the time of RTx. CONCLUSION: In a representative CRF
      population, BMD was reduced. Independent predictors of BMD were as for the
      general population, and uremia associated predictors were time on HD, previous
      transplantation and serum iPTH level. Fracture rate was high, and physical
      inactivity had the strongest association with fractures.

PMID- 18318738
TI  - What happens to the kidney in an SPK transplant when the pancreas fails due to a
      technical complication?
AB  - We examined a group of SPK recipients that had early (<90 d post-transplant)
      pancreas graft failure caused by a technical complication, and looked at outcomes
      of the kidney graft in these recipients. Of 289 SPK transplants, 36 (12.5%) had
      early pancreas graft failure because of a technical complication: thrombosis (n =
      16), leak (n = 5), infection (n = 14), and pancreatitis (n = 1). Once the
      pancreas was lost, there was a high incidence of subsequent kidney graft failure.
      Kidney graft survival in these 36 recipients was 71.4% at one yr and 59.5% at
      three yr, significantly inferior compared to recipients that did not have early
      failure of the pancreas (86% at one yr and 82% at three yr, p < 0.001). Of the 36
      recipients with early pancreas loss, 18 have gone on to failure of the kidney
      graft. Causes included thrombosis (n = 3), infection (n = 1), death with function
      (n = 6), chronic rejection (n = 4), ischemia (n = 1), and other (n = 3). Of the
      18 kidney graft failures, nine occurred within three months after loss of the
      pancreas graft, usually either because of graft thrombosis, or patient death
      (usually from systemic sepsis). Multivariate analysis showed technical failure of
      the pancreas to be the most significant risk factor for kidney graft loss (HR =
      2.08, p = 0.006).

PMID- 18318739
TI  - Split liver transplantation with extended right grafts under patient-oriented
      allocation policy. Single center matched-pair outcome analysis.
AB  - BACKGROUND: Split liver transplantation (SLT) is an established technique
      developed to optimize the number of available grafts. Few data are available on
      SLT with extended right liver grafts (eRLG) in the context of patient-oriented
      allocation policy. METHODS: Between July 1, 2001 and December 31, 2005, 12 whole
      liver graft (WLG) recipients were matched with 12 eRLG recipients according to
      their clinical status, indication and year of liver transplantation. RESULTS:
      There were no differences according to recipient Model for End-stage Liver
      Disease score, total serum bilirubin, creatinine levels and international
      normalized ratio in both groups. Fifty percent of donors in eRLG group presented
      2 or more extended criteria. Liver transplantation was performed in UNOS status
      1/2A in 58% of cases in both groups. Vascular and biliary complications were
      observed in three patients in the eRLG group. The median follow-up was 25.3
      months (range 0.4-63). Early mortality (<or=3 m) was 16.7% in WLG vs. 0% in eRLG,
      respectively (p = n.s.). Five-yr patient and graft survival rates were 84% and
      77%, and 75% and 68%, respectively, for WLG and eRLG. CONCLUSION: Split liver
      transplantation with eRLG according to the patient-oriented allocation policy can
      be performed under emergency or urgent care circumstances with acceptable
      morbidity and adequate long-term survival.

PMID- 18318740
TI  - Diffuse large B-cell lymphoma in a renal allograft associated with Epstein-Barr
      virus in the recipient: a case report and a review of lymphomas presenting in a
      transplanted kidney.
AB  - The purpose of this review was to evaluate the case reports with
      lymphoproliferative disorders exclusively localized in the allograft transplanted
      kidney. We also report a rare case of diffuse large B-cell lymphoma originated
      from the lymphocytes of the recipient with exclusive localization in the kidney
      allograft. We searched the medical literature for case reports of this condition.
      We found only 16 cases of lymphoma presenting in the kidney allograft without
      systemic affectation. The most frequent clinical manifestations were graft
      dysfunction and fever. In the majority of patients included in this review, the
      diagnosis was established from the tissue of explanted allograft. Seven patients
      were diagnosed with B-cell lymphoma, and the relationship with Epstein-Barr virus
      could only be demonstrated in four patients. However, the outcome was
      satisfactory in all cases, except in one case in which death was not related with
      the lymphoma etiology. Health care providers should be aware of this clinical
      entity and heightened index of suspicion should be used so as not to delay
      diagnosis and not to lose the allograft.

PMID- 18318741
TI  - Determinants and patterns of renin-angiotensin system inhibitors' prescription in
      the first year following kidney transplantation.
AB  - The benefit of prescribing angiotensin-converting enzyme inhibitors (ACEi) and
      angiotensin-II receptor antagonists (ARB) to kidney transplant recipients remains
      controversial. We investigated determinants and prescribing patterns of ACEi/ARB
      during the first year following kidney transplantation. All recipients of a first
      kidney transplant performed at the university hospital of Nancy (France) between
      January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription
      were identified by Cox models among various recipient characteristics (at
      transplantation and during follow-up), donor characteristics and transplant
      parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after
      transplantation, and 26.9% were taking them at one yr. Recipient determinants of
      ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre-transplant hypertension
      (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post
      transplant proteinuria (HR: 1.62, p < 0.0001) and anemia (HR: 4.08, p < 0.0001).
      Glomerular filtration rate level was not associated with ACEi/ARB use. Post
      transplant hypercholesterolemia (HR: 0.42, p = 0.013) and higher donor age (HR:
      0.98, p = 0.015) were associated with a lower likelihood of ACEi/ARB use. Fewer
      HLA mismatches (HR: 1.16, p = 0.029) and shorter cold ischemia duration (HR:
      1.02, p = 0.045) were also independent predictors of ACEi/ARB use. Regardless of
      recipient characteristics, nephrologists were more likely to prescribe ACEi/ARB
      after kidney transplantation when the transplant parameters were favorable.

PMID- 18318742
TI  - Central venous catheter removal from patients with candidaemia.

PMID- 18318743
TI  - Invasive infections caused by Neisseria meningitidis, Haemophilus influenzae and
      Streptococcus pneumoniae among children in St Petersburg, Russia.
AB  - This study investigated the causes of invasive bacterial infections in children
      aged <15 years in St Petersburg, Russia, during 2001-2003, using culture and
      antigen detection methods (rapid antigen latex agglutination (RAL)) for normally
      sterile body fluids. A pathogen was detected in 90 cases (culture 50, RAL 40).
      Neisseria meningitidis was the most common pathogen (66%), followed by
      Haemophilus influenzae (19%) and Streptococcus pneumoniae (16%). Meningitis was
      the main clinical diagnosis (68/90, 76%), with N. meningitidis serogroup B, H.
      influenzae type b (Hib), and S. pneumoniae serogroup 1 being the most common
      isolates. Hib was less prevalent in St Petersburg than it was in industrialised
      countries before the introduction of Hib vaccinations.

PMID- 18318744
TI  - Performance of two tube coagulase methods for rapid identification of
      Staphylococcus aureus from blood cultures and their impact on antimicrobial
      management.
AB  - Test parameters and clinical impact of the direct tube coagulase test (DTCT) for
      rapid identification of Staphylococcus aureus from blood culture were
      investigated. The sensitivity of the DTCT at 4 h using saline dilution was 96%,
      compared with 93% using serum separator tubes; specificity was 100% for both
      methods. Among 32 patients with S. aureus bacteraemia, treatment modifications
      were based on microbiology results from the primary source of infection in 12
      patients, on a Gram's stain from blood culture in seven patients, and on the DTCT
      in nine patients. The DTCT is a valuable adjunct in the routine microbiology
      laboratory because of its good performance, technical simplicity and low cost.

PMID- 18318745
TI  - Anti-oxidant activity mediated neuroprotective potential of trimetazidine on
      focal cerebral ischaemia-reperfusion injury in rats.
AB  - 1. The present study was designed to investigate the neuroprotective effect of
      trimetazidine (TMZ) following focal cerebral ischaemia-reperfusion (I/R) injury
      in rat forebrain. 2. Cerebral I/R injury was induced in rats by middle cerebral
      artery occlusion (MCAO) for 2 h, followed by reperfusion for 22 h. Trimetazidine
      (5 and 25 mg/kg, i.p.) was administered 1 h after induction of MCAO. The effects
      of TMZ were investigated by measuring neurological deficit, volume of infarct and
      brain swelling after 22 h reperfusion. Oxidative stress and inflammatory
      reactivity were assessed by estimating anti-oxidant markers and myeloperoxidase
      (MPO) activity in brain homogenates. Rectal temperature was measured during the
      study. The effects of TMZ on blood-brain barrier (BBB) permeability and apoptosis
      were also investigated in rat brain. Apoptosis was observed by DNA fragmentation
      studies using agarose gel electrophoresis. 3. Treatment with TMZ significantly (P
      < 0.01) reduced infarct volume and brain swelling. Superoxide dismutase (SOD)
      activity was reduced in ipsilateral hemispheres of vehicle (saline)-treated
      reperfused (RI) animals. Treatment with TMZ significantly restored SOD activity
      (P < 0.01) and glutathione levels (P < 0.05) after reperfusion compared with RI
      animals. Lipid peroxidation, MPO activity, BBB permeability and rectal
      temperature were all significantly (P < 0.01, P < 0.05 and P < 0.001,
      respectively) reduced in TMZ-treated animals compared with RI animals. 4. These
      results suggest that TMZ protects the brain against cerebral I/R injury and that
      this neuroprotective activity could be mediated by its anti-oxidant properties.
      The reduction in rectal temperature by TMZ treatment may be responsible for
      maintaining the delicate energy balance during I/R injury in rat brain and could
      have contributed to the neuroprotective activity of TMZ.

PMID- 18318746
TI  - Effectiveness of an educational and physical programme in reducing headache, neck
      and shoulder pain: a workplace controlled trial.
AB  - This study was an 8-month controlled trial to evaluate the effectiveness of a
      workplace educational and physical programme in reducing headache and neck and
      shoulder pain. Central registry office employees (n = 192; study group) and 192
      peripheral registry office and central tax office employees (controls) in the
      city of Turin, Italy were given diaries for the daily recording of pain episodes.
      After 2 months, the study group only began the educational and physical
      programme. The primary end-point was the change in frequency of headache and neck
      and shoulder pain expressed as the number of days per month with pain, and as the
      proportion of subjects with a >or= 50% reduction of frequency (responder rate).
      The number of days of analgesic drug consumption was also recorded. Diaries
      completed for the whole 8 months were available for 169 subjects in the study
      group and 175 controls. The baseline frequency of headache (days per month) was
      5.87 and 6.30 in the study group and in controls; frequency of neck and shoulder
      pain was 7.12 and 7.79, respectively. Mean treatment effects [days per month, 95%
      confidence interval (CI)] on comparing the last 2 months vs. baseline were:
      headache frequency -2.45 (-3.48, -1.43); frequency of neck pain -2.62 (-4.09, 
      1.16); responder rates (odds ratio, 95% CI) 5.51 (2.75, 11) for headache, 3.10
      (1.65, 5.81) for neck and shoulder pain, and 3.08 (1.06, 8.90) for days with
      analgesic drug consumption. The study suggests that an educational and physical
      programme reduces headache and neck and shoulder pain in a working community.

PMID- 18318747
TI  - The role of cervical dysfunction in migraine: a systematic review.
AB  - This systematic review evaluates the strength of the evidence for the role of
      cervical musculoskeletal dysfunction in migraine. In this review, cervical
      musculoskeletal dysfunction will refer to the abnormal sensory afferentation from
      cervical region structures contained within the receptive field of the
      trigeminocervical nucleus. Electronic database searches using MEDLINE, PubMed and
      CINAHL were performed, and 17 studies investigating cervical musculoskeletal
      dysfunction in people with migraine were selected for review. The methodological
      quality of the included studies was assessed by two independent reviewers using a
      customized checklist. The review found that intersubject differences were
      inadequately reported and controlled, which resulted in grouping of participants
      with varying pathologies and symptoms. A diverse range of assessment procedures
      was used by the reviewed studies, which made comparison of their findings
      difficult. The assessment procedures were mainly used to quantify the degree of
      cervical musculoskeletal dysfunction, rather than to identify a cause and effect
      relationship between cervical structure and migrainous pain. Although animal
      study evidence proposes a role for cervical musculoskeletal dysfunction in
      migraine, this systematic review of the literature found that there is currently
      no convincing evidence to confirm this phenomenon in humans.

PMID- 18318748
TI  - Occipital neuralgia with cervical myelitis.

PMID- 18318749
TI  - Bath-related thunderclap headache: a study of 21 consecutive patients.
AB  - We consecutively recruited 21 patients (all women, mean 54 +/- 8 years) with bath
      related thunderclap headache (BRTH). Thirteen of them were in menopause, two had
      just ceased hormonal therapy, and one was at 3 months postpartum. Bathing was the
      initial trigger for thunderclap headaches in nine patients (43%). Many patients
      (n = 15, 71%) had other non-bath-related attacks. Most patients (n = 18, 86%)
      reported that the headache occurred immediately when water was sprayed over their
      body, with warm water (52%) as the most common. During the disease course [mean
      14 days (6-34)], the mean number of BRTH was 5.1 +/- 3.6 attacks. Nineteen
      patients (90%) changed bathing habits to prevent attacks. Thirteen patients (62%)
      had magnetic resonance angiography vasoconstrictions, and two of them (15%)
      developed reversible posterior encephalopathy. None of the patients without
      vasoconstrictions had this complication. Nimodipine was effective in stopping
      further attacks in 84% (16/19) treated patients. No relapse was reported at a
      mean follow-up of 30 months. BRTH occurred exclusively in women and predominantly
      in middle age. Deficiency or fluctuation of female sex hormones may play a role.
      About 60% patients showed cerebral vasospasms, fulfilling the diagnosis of
      reversible cerebral vasoconstriction syndrome and indicating a risk of posterior
      encephalopathy.

PMID- 18318750
TI  - Human blood dendritic cells from allergic subjects have impaired capacity to
      produce interferon-alpha via Toll-like receptor 9.
AB  - BACKGROUND: High-affinity IgE receptor (Fc epsilon RI) expression on blood
      dendritic cells reportedly correlates with serum IgE levels. Our studies
      demonstrate that plasmacytoid dendritic cells (pDCs) secrete pro-inflammatory
      cytokines (IL-6, TNF-alpha) following Fc epsilon RI stimulation - a mode of
      activation that simultaneously reduces expression of Toll-like receptor 9 (TLR9).
      Whether or not TLR9 and/or Fc epsilon RI levels and their function on dendritic
      cells relate to allergic status is unknown. OBJECTIVE: The aim of this study is
      to compare the innate (TLR9-mediated) immune response of human pDCs to TLR9 and
      Fc epsilon RI alpha receptor expression in allergic and non-allergic subjects.
      METHODS: Basophil-depleted mononuclear cell fractions containing pDCs were
      prepared from peripheral blood of allergic and non-allergic subjects.
      Intracellular TLR9 and surface Fc epsilon RI alpha expression in blood dendritic
      cell antigen-2-positive cells were determined by flow cytometry. Activating anti
      IgE antibody, anti-Fc epsilon RI alpha antibody, and TLR9 agonist were used to
      stimulate cell suspensions, with cytokine levels determined by ELISA. RESULTS: No
      difference in the frequency of pDCs was detected among allergic (n=9) vs. non
      allergic (n=11) subjects (P=0.261). While there was also no difference in the
      baseline expression of TLR9, pDCs from allergic subjects produced sixfold less
      IFN-alpha when stimulated with CpG (P=0.002). Conversely, there was higher Fc
      epsilon RI alpha expression (P=0.01) on the pDCs of allergic subjects.
      CONCLUSIONS: Impaired TLR9-dependent immune responses in human pDCs are
      associated with allergic status and inversely correlated with Fc epsilon RI alpha
      expression. This impaired innate immune response among dendritic cells of
      allergic subjects may lead to more targeted therapeutic approaches and could
      provide a better understanding of the mechanisms underlying conventional and CpG
      based immunotherapy.

PMID- 18318751
TI  - Implementation of the scientific evidence into daily practice--example from fast
      track colonic cancer surgery.
AB  - OBJECTIVE: To report the implementation and results of fast-track surgery for
      colonic cancer in the daily routine. METHOD: A total of 131 consecutive patients
      scheduled for elective colonic cancer resections entered a fast-track
      perioperative course after thorough information. The regimen contained: no
      preoperative bowel cleansing, transverse and small abdominal incisions, no drains
      nor tubes, mobilization and normal meal the evening on the day of surgery,
      epidural analgesia, oral laxatives, and a planned discharge on postoperative day
      3. RESULTS: Median number of days postoperative in hospital were 4 days (range 1
      46). Eighty-nine per cent experienced an uncomplicated course, 3% were readmitted
      within 30 days, and the 30-day mortality was 3.8%. CONCLUSION: Fast-track surgery
      is feasible in an unselected patient population scheduled for elective colon
      cancer resections without compromising quality.

PMID- 18318752
TI  - Risk factors for anastomotic leakage after rectal cancer surgery: a case-control
      study.
AB  - BACKGROUND: With introduction of the total mesorectal excision technique and
      preoperative radiotherapy in rectal cancer surgery, the local recurrence rate has
      decreased and the overall survival has improved. One drawback, however, is the
      high anastomotic leakage rate of approximately 10-18%. Male gender and low
      anastomoses are known risk factors for such leakage. The aim of this study was to
      identify potentially modifiable risk factors. METHOD: In a case-control study,
      data from the Swedish Rectal Cancer Registry (1995-2000) were analysed. Cases
      were all patients with anastomotic leakage after an anterior resection (n = 134).
      Two controls were randomly selected for each case. The medical records (n = 402)
      were checked against a study protocol. Due to incorrect recording two cases and
      28 controls were excluded from further analyses. RESULTS: In the multivariate
      analysis significant risk factors were American Society of Anesthesiologists
      score > 2 [OR = 1.40 (95% CI 1.05-1.83)], preoperative radiotherapy [OR = 1.34
      (95% CI 1.06-1.69)], intraoperative adverse events [OR = 1.85 (95% CI 1.32
      2.58)], level of anastomosis <or= 6 cm [OR = 1.39 (95% CI 1.01-1.90)] and severe
      bleeding [OR = 1.45 (95% CI 1.14-1.84)]. Diverting stoma protected from leakage
      [OR = 0.68 (95% CI 0.52-0.88)]. Male gender was a risk factor in the univariate
      but not in the multivariate analysis [OR = 1.30 (95% CI 1.04-1.63) and OR = 1.26
      (95% CI 1.00-1.58), respectively]. Except for a protective stoma, none of the
      variables considered as possible targets for improvement, such as postoperative
      epidural anaesthesia, observation at intensive care unit for more than 24 h, and
      intraabdominal drainage, proved to be protective factors either in the univariate
      or in the multivariate analyses. CONCLUSION: The most important risk factors for
      leakage were adverse intraoperative events, low anastomoses and preoperative
      radiotherapy. A diverting stoma is protective and can reduce the consequences
      when leakage occurs. Further analyses with focus on the surgical technique and
      individual surgeon may be valuable in identifying targets for improvement.

PMID- 18318754
TI  - Magnetic resonance imaging in rectal cancer downstaged using neoadjuvant
      chemoradiation: accuracy of prediction of tumour stage and circumferential
      resection margin status.
AB  - OBJECTIVE: The aim was to examine the accuracy of magnetic resonance imaging
      (MRI) in predicting circumferential resection margin (CRM) involvement, T- and N
      stage in patients with locally advanced carcinoma of the rectum, who had
      undergone long-course downstaging chemoradiation (CRT). METHOD: Patients with
      rectal cancer were selected for long-course downstaging CRT if their tumour was
      considered to threaten (< or = 1 mm) or involve the CRM on MRI. Eighty such
      patients had a repeat MRI at a median of 6 weeks post-CRT followed by surgical
      excision soon thereafter. The findings on the post-CRT MRI were compared with
      histological examination of the surgical specimen. RESULTS: For CRM involvement,
      post-CRT restaging MRI had an accuracy of 81% (65/80) a sensitivity of 54%
      (7/13), a specificity of 87% (58/67), a positive predictive value of 44% (7/16)
      and a negative predictive value of 91% (58/64). Accuracy for T- and N-staging was
      43% (34/80) and 78% (62/80), respectively. 38% of T-stages were overstaged and
      20% understaged. 4% of N-stages were overstaged and 19% understaged. The 13
      patients with histological positive CRM had worse clinical outcomes than the 67
      patients with negative CRM in terms of disease-free survival (relative risk of
      reduced DFS 4.6, P = 0.001) and overall survival (relative risk of death 3.6, P =
      0.016). CONCLUSION: Magnetic resonance imaging has good specificity and negative
      predictive value for predicting an uninvolved CRM post downstaging CRT in locally
      advanced rectal cancer although sensitivity and positive predictive value for an
      involved CRM were unsatisfactory. The shortcomings of MRI stem from poor
      differentiation of viable tumour from posttreatment changes and inability to
      identify small nodal and tumour deposits. Clinical correlates in this group of
      patients have confirmed the importance of achieving a clear CRM at surgery.

PMID- 18318755
TI  - Colonoscopy for screening and follow up of patients with a family history of
      colorectal cancer.
AB  - OBJECTIVE: To determine the minimum family history of colorectal cancer (CRC),
      which justifies colonoscopy and to establish whether further colonic assessment
      is necessary after a negative screening colonoscopy. METHOD: A retrospective
      review of every colonoscopy undertaken for family screening at the Royal
      Berkshire and Battle Hospitals, Reading between October 1996 and July 2004.
      RESULTS: Four hundred and thirty-two patients (261 women) with an average age of
      48 years (range 14-84) were screened. Three cancers in patients over the age of
      60 years and 49 adenomas were found in 37 patients. Twenty three of 281 (8%)
      patients with a 'low-risk' family history (one in 12 or less lifetime risk of
      developing CRC) had either a cancer or an adenoma. Eighteen of 151 (12%) patients
      with a 'high-risk' family history (one in 10 or greater) had a similar positive
      colonoscopy. Thirteen of 15 patients who had an adenoma aged under 45 years had a
      high-risk family history. Seventy-three patients subsequently underwent two or
      more follow-up colonoscopies. There were 22 adenomatous polyps found in 12
      patients (16%) at the first screening, nine adenomas in seven patients in the
      second colonoscopy and four adenomas found in four patients in all subsequent
      colonoscopies. CONCLUSION: Patients with a low-risk family history have a similar
      adenoma pick-up to that of the general population. These patients need not be
      screened below the age of 50 unless symptomatic. Follow up of low-risk family
      history (FH) patients with a negative screening colonoscopy is unlikely to be
      beneficial.

PMID- 18318753
TI  - Involvement of surgical trainees in surgery for colorectal cancer and their
      effect on outcome.
AB  - OBJECTIVE: Surgical training in the UK is undergoing substantial changes. This
      study assessed: 1) the training opportunities available to trainees in operations
      for colorectal cancer, 2) the effect of colorectal specialization on training,
      and 3) the effect of consultant supervision on anastomotic complications,
      postoperative stay, operative mortality and 5-year survival. METHOD: Unadjusted
      and adjusted comparisons of outcomes were made for unsupervised trainees,
      supervised trainees and consultants as the primary surgeon in 7411 operated
      patients included in the Northern Region Colorectal Cancer Audit between 1998 and
      2002. RESULTS: Surgery was performed in 656 (8.8%) patients by unsupervised
      trainees and in 1578 (21.3%) patients by supervised trainees. Unsupervised
      operations reduced from 182 (12.4%) in 1998 to 82 (6.1%) in 2002 (P < 0.001).
      Consultants with a colorectal specialist interest were more likely than
      nonspecialists to be present at surgical resections (OR 1.35, 1.12-1.63, P =
      0.001) and to provide supervised training (OR 1.34, 1.17-1.53, P < 0.001).
      Patients operated on by unsupervised trainees were more often high-risk patients,
      however, consultant presence was not significantly associated with operative
      mortality (OR 0.83, 0.63-1.09, P = 0.186) or survival (HR 1.02, 0.92-1.13, P =
      0.735) in risk-adjusted analysis. Supervised trainees had a case-mix similar to
      consultants, with shorter length of hospital stay (11.4 vs 12.4 days, P < 0.001),
      but similar mortality (OR 0.90, 0.71-1.16, 0.418) and survival (HR 0.96, 0.89
      1.05, P = 0.378). CONCLUSION: One third of patients were operated on by trainees,
      who were more likely to perform supervised resections in colorectal teams. There
      was no difference in anastomotic leaks rates, operative mortality or survival
      between unsupervised trainees, supervised trainees and consultants when case-mix
      adjustment was applied. This study would suggest that there is considerable
      underused training capacity available.

PMID- 18318756
TI  - Effect of deferasirox (ICL670) on arterial function in patients with beta
      thalassaemia major.
AB  - Deferasirox (ICL670) has been shown to have rapid accessibility to intracellular
      labile iron. We tested the hypothesis that oral deferasirox improves arterial
      dysfunction in patients with beta-thalassaemia major. Nineteen thalassaemia
      patients, aged 23 +/- 7 years, with normal left ventricular (LV) function were
      treated with deferasirox at 25-35 mg/kg/d for 12 months. LV function, brachial
      arterial flow-mediated dilation (FMD), carotid arterial stiffness, and serum
      ferritin levels were determined at baseline prior to initiation, after 6 months
      and after 12 months of therapy. The baseline cardiovascular indices were compared
      with those of 17 age-matched controls. Longitudinal changes in patients during
      the treatment period were also determined. Compared with controls, patients had
      similar echocardiographic indices of LV function (all P > 0.05), while their
      baseline brachial FMD was reduced (P < 0.001) and carotid stiffness increased (P
      = 0.019). An increase in FMD (P < 0.001) and a decrease in carotid stiffness (P =
      0.007) were found at 6 and 12 months follow-up. The stiffness index correlated
      inversely with FMD (r = -0.42, P = 0.001). Although there was an increase in
      ferritin level at 12 months (3303 +/- 1185 ng/ml vs. 2714 +/- 780 ng/ml at
      baseline, P = 0.006), no significant correlation existed between ferritin level
      and FMD or carotid stiffness. In conclusion, deferasirox therapy in thalassaemia
      patients is associated with improved arterial function.

PMID- 18318757
TI  - The evolving use of serum free light chain assays in haematology.
AB  - Over the last few years new immunoassays have emerged that allow the measurement
      of free immunoglobulin light chains (FLCs) in serum to a level of 2-4 mg/l and
      provide a much greater sensitivity than older methods, such as immunofixation,
      which is able to detect FLCs at a minimum concentration of 100-150 mg/l. The new
      FLC assay has enabled the detection of monoclonal protein in some patients with
      non-secretory myeloma and amyloidosis that were previously undetectable. FLC
      measurements are quantitative, correlating with disease activity, and are an
      advance in monitoring light chain only multiple myeloma, AL amyloidosis, non
      secretory and oligo-secretory multiple myeloma. Serum FLC concentrations also
      reflect the disease course in the majority of myeloma patients producing intact
      monoclonal immunoglobulin proteins and have been incorporated into the new
      response criteria. The rapid half life of lambda and kappa free light chains
      means that FLC assays may provide a more rapid indication of the response to
      treatment but their clinical utility in this setting needs further study. An
      abnormal FLC ratio has been shown to be a risk factor for progression of
      monoclonal gammopathy of undetermined significance, smouldering myeloma and
      solitary plasmacytoma of bone and is prognostic in multiple myeloma.

PMID- 18318758
TI  - Detection of elevated levels of tumour-associated microRNAs in serum of patients
      with diffuse large B-cell lymphoma.
AB  - Circulating nucleic acids have been shown to have potential as non-invasive
      diagnostic markers in cancer. We therefore investigated whether microRNAs also
      have diagnostic utility by comparing levels of tumour-associated MIRN155 (miR
      155), MIRN210 (miR-210) and MIRN21 (miR-21) in serum from diffuse large B-cell
      lymphoma (DLBCL) patients (n = 60) with healthy controls (n = 43). Levels were
      higher in patient than control sera (P = 0.009, 0.02 and 0.04 respectively).
      Moreover, high MIRN21 expression was associated with relapse-free survival (P =
      0.05). This is the first description of circulating microRNAs and suggests that
      microRNAs have potential as non-invasive diagnostic markers for DLBCL and
      possibly other cancers.

PMID- 18318759
TI  - Prospective study of homocysteine and MTHFR 677TT genotype and risk for venous
      thrombosis in a general population--results from the HUNT 2 study.
AB  - This case-cohort designed study prospectively investigated whether elevated
      homocysteine levels measured in blood samples drawn before the event and
      methylenetetrahydrofolate reductase (MTHFR) gene polymorphism (MTHFR C677T) were
      associated with subsequent first venous thrombosis (VT) in a general population.
      Between August 1995 and June 1997, blood was collected from 66 140 people in the
      second Norwegian Health Study of Nord-Trondelag (HUNT2). During a seven-year
      follow-up, 505 VT cases were identified. 1458 age- and sex-matched controls were
      selected from the original cohort. Serum total homocysteine (tHcy) and MTHFR
      genotype were measured in stored samples that were drawn a median of 33 months
      before the events. The overall odds ratio (OR) was 1.50 [95% confidence interval
      (CI) 0.97-2.30] for homocysteine levels above versus below the 95th percentile.
      There was no graded association with VT over quintiles of homocysteine. In men
      the OR was 2.17 (95% CI 1.20-3.91) for levels above versus below the 95th
      percentile, but no association was found in women (OR 1.00). Stratification by
      age, predisposing risk factors or time to event did not change these results. The
      MTHFR 677TT genotype was not related to risk for VT. In conclusion, elevated
      homocysteine levels in the general population predicted subsequent first VT in
      men but not in women.

PMID- 18318760
TI  - Epigenetic inactivation of suppressors of cytokine signalling in Philadelphia
      negative chronic myeloproliferative disorders.
AB  - Ph-negative chronic myeloproliferative disorders (CMPD) are characterized by
      constitutive Janus kinase-signal transducer and activator of transcription (JAK
      STAT) activation. SOCS3, SOCS1 and PTPN6 (SHP1) are negative regulators of the
      JAK-STAT pathway. We investigated epigenetic and genetic inactivation of SOCS3,
      SOCS1 and PTPN6 in 112 CMPD and 20 acute myeloid leukaemia (AML) post-CMPD. SOCS3
      methylation occurred at high frequency in both CMPD (46/112; 41.1%) and AML post
      CMPD (10/17; 58.8%) and was associated with transcriptional silencing. In
      contrast, methylation of SOCS1 and PTPN6 was observed in only a fraction of CMPD
      (15/112, 13.4% for SOCS1; and 8/112, 7.1% for PTPN6) and AML post-CMPD (3/20, 15%
      for SOCS1; and 1/20, 5% for PTPN6). No somatic mutations of SOCS1 were found in
      CMPD. SOCS3, SOCS1 and PTPN6 methylation occurred in both JAK2V617F-positive
      (35.1% for SOCS3; 14.9% for SOCS1; 8.1% for PTPN6) and JAK2V617F-negative (57.1%
      for SOCS3; 14.3% for SOCS1; and 9.5% for PTPN6) CMPD. These data indicate that
      methylation of SOCS3 and, to a lesser extent, SOCS1 and PTPN6 is a frequent event
      in both JAK2V617F-positive and -negative CMPD and may act as an alternative or
      complementary mechanism to JAK2 mutations, enhancing cytokine signal
      transduction. The frequent inactivation of SOCS3 is a novel finding in CMPD with
      potential implications for the molecular pathology of these disorders.

PMID- 18318761
TI  - Outcome after autologous stem cell transplantation for multiple myeloma in
      patients with preceding plasma cell disorders.
AB  - A third of patients with multiple myeloma (MM) have a preceding diagnosis of
      plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of
      undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While
      autologous stem cell transplantation (SCT) improves survival in MM, it is not
      clear if patients with preceding PCPD have a different outcome. We identified 151
      patients with preceding PCPD from among 804 patients undergoing SCT, and their
      outcomes were compared. The response rates, including complete responses, were
      similar between the groups. Patients with a preceding diagnosis of MGUS had
      longer time to progression (TTP; 27.5 months vs. 17.2 months, P = 0.01), and
      longer overall survival (OS) from transplant (80.2 months vs. 48.3 months, P =
      0.03) compared to those with de novo myeloma. However no differences were seen
      among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or
      OS from transplant when compared to those with de novo myeloma. Multivariate
      analysis indicated that the presence of MGUS prior to myeloma was prognostic for
      post-transplant relapse independent of other known risk factors. Patients with
      pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT,
      reflecting more indolent disease and a favourable biology than those presenting
      with de novo myeloma.

PMID- 18318762
TI  - Outcome of BEAM-autologous and BEAM-alemtuzumab allogeneic transplantation in
      relapsed advanced stage follicular lymphoma.
AB  - The role of haematopoietic stem cell transplantation (HSCT) in relapsed
      follicular lymphoma remains controversial. This study analysed 126 patients with
      relapsed, advanced stage follicular lymphoma who received BEAM (BCNU
      [carmustine], cytarabine, etoposide, melphalan)-alemtuzumab allogeneic HSCT (BEAM
      allo) (n = 44) or BEAM-autologous HSCT (BEAM-auto) (n = 82). The BEAM-allo group
      had a younger median age (48 years vs. 56 years, P < 0.001) but received a higher
      median number of therapies pretransplant (P = 0.015) compared with the BEAM-auto
      group. There was a higher non-relapse mortality (NRM) in the BEAM-allo group
      compared with the BEAM-auto group at 1 year (20% vs. 2%, P = 0.001). Older age
      and heavily pretreated patients were associated with a higher NRM and poorer
      survival in the BEAM-allo group. There was, however, a significantly lower
      relapse rate (20% vs. 43%, P = 0.01) at 3 years with BEAM-alemtuzumab, with no
      relapses after 2 years, compared with a continued pattern of relapse in the
      autologous group. No difference in overall survival (OS) (P = 0.99) or disease
      free survival (DFS) (P = 0.90) was identified at 3 years, whereas a plateau in OS
      and DFS with crossing of the survival curves in favour of BEAM-allo group was
      observed. Furthermore, the ability to re-induce remissions with donor leucocytes
      provides additional benefit in favour of allogeneic HSCT.

PMID- 18318763
TI  - A mechanism for Ikaros regulation of human globin gene switching.
AB  - The human beta globin locus consists of an upstream LCR and functional genes
      arranged sequentially in the order of their expression during development: 5'
      HBE1, HBG2, HBG1, HBD, HBB-3'. Haemoglobin switching entails the successive
      recruitment of these genes into an active chromatin hub (ACH). Here we show that
      the transcription factor Ikaros plays a major role in the formation of the beta
      globin ACH, and in haemoglobin switching. In Plastic mice, where the DNA-binding
      region of Ikaros is disrupted by a point mutation, there is concomitant marked
      down-regulation of HBB, and up-regulation of HBG expression. We show for the
      first time Ikaros and its family member Eos, bind to critical cis elements
      implicated in haemoglobin switching and deletional hereditary persistence of
      fetal haemoglobin (HPFH). Chromatin conformation capture (3C) data demonstrated
      that Ikaros facilitates long-distance DNA looping between the LCR and a region
      upstream of HBD. This study provides new insights into the mechanism of stage
      specific assembly of the beta-globin ACH, and HPFH.

PMID- 18318764
TI  - ACE I/D polymorphism and recurrent first trimester pregnancy loss: interaction
      with SERPINE1 4G/5G and F13 Val34Leu polymorphisms.

PMID- 18318765
TI  - Rituximab in the treatment of autoimmune haematological disorders.
AB  - Current treatment regimens for haematological autoimmune diseases are relatively
      non-selective and are often associated with considerable toxicity. Recently, it
      has become clear that B cells play a key role in both the development and
      perpetuation of autoimmunity, suggesting that B-cell depletion could be a
      valuable treatment approach for patients with autoimmune diseases. This article
      reviews data supporting the use of rituximab--an anti-CD20 monoclonal antibody
      that specifically depletes B cells--in four key autoimmune haematological
      disorders: idiopathic thrombocytopenic purpura (ITP); autoimmune haemolytic
      anaemia (AIHA); acquired haemophilia; and thrombotic thrombocytopenic purpura
      (TTP). Although treatment of ITP, AIHA, acquired haemophilia and TTP with
      rituximab is still relatively uncommon, results from case series and small phase
      II trials indicate that patients of all ages can respond to rituximab,
      irrespective of the number or type of prior treatments that they have received.
      Moreover, patients with these diseases receiving rituximab experienced
      predominantly mild adverse events, with only a few serious adverse events
      reported. These data suggest that rituximab provides an effective and well
      tolerated alternative treatment option for patients with ITP, AIHA, acquired
      haemophilia and TTP, many of whom have limited treatment choices.

PMID- 18318766
TI  - Intracranial small lymphocytic lymphoma.

PMID- 18318767
TI  - Fetal haemoglobin response to hydroxycarbamide treatment and sar1a promoter
      polymorphisms in sickle cell anaemia.
AB  - The hydroxycarbamide (HC)-inducible small guanosine triphosphate (GTP)-binding
      protein, secretion-associated and RAS-related (SAR) protein has recently been
      shown to play a pivotal role in HBG induction and erythroid maturation by causing
      cell apoptosis and G1/S-phase arrest. Our preliminary analysis indicated that HC
      inducibility is transcriptionally regulated by elements within the SAR1A
      promoter. This study aimed to assess whether polymorphisms in the SAR1A promoter
      are associated with differences Hb F levels or HC therapeutic responses among
      sickle cell disease (SCD) patients. We studied 386 individuals with SCD comprised
      of 269 adults treated with or without HC and 117 newborns with SCD identified
      from a newborn screening program. Three previously unknown single nucleotide
      polymorphisms (SNPs) in the upstream 5'UTR (-809 C>T, -502 G>T and -385 C>A) were
      significantly associated with the fetal haemoglobin (HbF) response in Hb SS
      patients treated with HC (P < 0.05). In addition, four SNPs (rs2310991, -809 C>T,
      -385 C>A and rs4282891) were significantly associated with the change in absolute
      HbF after 2 years of treatment with HC. These data suggest that variation within
      SAR1A regulatory elements might contribute to inter-individual differences in
      regulation of HbF expression and patient responses to HC in SCD.

PMID- 18318768
TI  - Murine bone marrow derived stromal progenitor cells fail to prevent or treat
      acute graft-versus-host disease.
AB  - Human and murine stromal progenitor cells (SPCs) can suppress alloresponse in
      vitro, suggesting that SPCs may have clinical application toward prevention or
      treatment of graft-versus-host disease (GVHD). However, th eresults of in vivo
      studies have been conflicting. This study utilized an established murine model of
      acute GVHD to assess the ability of bone marrow derived murine SPCs (mSPCs) to
      prevent or treat GVHD. GVHD was established by transplantation of B6 bone marrow
      and spleen cells into lethally irradiated (900 cGy) B6 x BALB/c F(1) recipients.
      mSPCs were administered using various dose and timing protocols designed to
      either prevent or treat GVHD. After transplantation, mice were monitored daily
      for weight and survival. Differences in symptom severity were compared using a
      clinical GVHD scoring system. All GVHD control mice died of lethal GVHD. All
      groups treated with mSPCs for the prevention of GVHD went on to develop clinical
      GVHD with no alteration of the disease course or severity compared to controls.
      Administration of mSPC after the development of GVHD failed to improve the
      disease course. We conclude that in this model, the ability of SPCs to suppress
      alloresponse in vitro does not correlate with in vivo prevention or treatment of
      acute GVHD.

PMID- 18318769
TI  - Anti-CD20 monoclonal antibody therapy in multiple myeloma.
AB  - CD20 is a particularly appealing target that is expressed on the surface of
      almost all B cells, with no significant shedding, secretion or internalization.
      In contrast to the demonstrated efficacy of anti-CD20 strategies in various B
      cell lymphoproliferative disorders, the role of such therapy in multiple myeloma
      is undetermined and controversial. The expression of CD20 by myeloma cells is
      heterogeneous, and can be detected only in 13-22% of patients. However, there is
      increasing interest in testing anti-CD20 therapy in myeloma because of recent
      studies suggesting the existence of clonogenic CD20-positive precursor B cells in
      the disease. This article reviews the rationale, preclinical and clinical
      activity of anti-CD20 therapy in myeloma. Clinical trials show that anti-CD20
      therapy with rituximab elicits a partial response in approximately 10% of CD20+
      patients with multiple myeloma. In addition, there is preliminary evidence of
      disease stabilization in 50-57% of CD20+ patients for a period of 10-27 months.
      Further large-scale clinical trials are therefore needed to establish the role of
      this promising strategy in the treatment of myeloma.

PMID- 18318770
TI  - Double-negative regulatory T cells induce allotolerance when expanded after
      allogeneic haematopoietic stem cell transplantation.
AB  - Double-negative (DN) regulatory T cells (Tregs) are specialized T lymphocytes
      involved in the down-modulation of immune responses, resulting in allotolerance
      after allogeneic haematopoietic stem cell transplantation (HSCT). Most of the
      properties of DN Tregs were identified in murine models, including the unique
      ability to suppress alloreactive syngeneic effector T cells in an antigen
      specific manner via Fas/Fas-ligand interactions. We investigated the behaviour of
      DN Tregs following human allogeneic HSCT with regard to occurrence of graft
      versus-host disease (GvHD) and restoration of T-cell receptor repertoire in a
      cohort of 40 patients. The frequency of DN Tregs and CD4/CD8 TCR repertoire was
      measured serially and at the time of diagnosis of GvHD by flow cytometry.
      Analysis demonstrated a positive correlation between degree of alloreactivity, as
      measured by grade of GvHD, and the number of variable beta chain (Vbeta) family
      expansions in both T-cell populations. We also found that a deficiency of DN
      Tregs was associated with an increased number of Vbeta family expansions, and
      most importantly, with the occurrence of GvHD. All individuals who demonstrated
      more than 1% DN Tregs did not develop GvHD, providing evidence that DN Tregs
      participate in peripheral tolerance to prevent GvHD when expanded after
      allogeneic HSCT.

PMID- 18318771
TI  - Recessive congenital methaemoglobinaemia: cytochrome b(5) reductase deficiency.
AB  - Some 60 years ago, Quentin Gibson reported the first hereditary disorder
      involving an enzyme when he deduced that familial methaemoglobinaemia was caused
      by an enzymatic lesion associated with the glycolysis pathway in red blood cells.
      This disorder, now known as recessive congenital methaemoglobinaemia (RCM), is
      caused by NADH-cytochrome b5 reductase (cb(5)r) deficiency. Two distinct clinical
      forms, types I and II, have been recognized, both characterized by cyanosis from
      birth. In type II, the cyanosis is accompanied by neurological impairment and
      reduced life expectancy. Cytochrome b(5) reductase is composed of one FAD and one
      NADH binding domain linked by a hinge region. It is encoded by the CYB5R3
      (previously known as DIA1) gene and more than 40 mutations have been described,
      some of which are common to both types of RCM. Mutations associated with type II
      tend to cause incorrect splicing, disruption of the active site or truncation of
      the protein. At present the description of the sequence variants of cb(5)r in the
      literature is confusing, due to the use of two conventions which differ by one
      codon position. Herein we propose a new system for nomenclature of cb(5)r based
      on recommendations of the Human Genome Variation Society. The development of a
      heterologous expression system has allowed the impact of naturally occurring
      variants of cb(5)r to be assessed and has provided insight into the function of
      cb(5)r.

PMID- 18318772
TI  - HIC1 tumour suppressor gene is suppressed in acute myeloid leukaemia and induced
      during granulocytic differentiation.
AB  - A hallmark of acute myeloid leukaemia (AML) is a block in differentiation caused
      by deregulated gene expression. The tumour suppressor Hypermethylated In Cancer 1
      (HIC1) is a transcriptional repressor, which is epigenetically silenced in solid
      cancers. HIC1 mRNA expression was found to be low in 128 patient samples of AML
      and CD34+ progenitor cells when compared with terminally differentiated
      granulocytes. HIC1 mRNA was induced in a patient with t(15;17)-positive acute
      promyelocytic leukaemia receiving all-trans retinoic acid (ATRA) therapy. We
      therefore investigated whether HIC1 plays a role in granulocytic differentiation
      and whether loss of function of this gene might contribute to the differentiation
      block in AML. We evaluated HIC1 mRNA levels in HL-60 and U-937 cells upon ATRA
      induced differentiation and in CD34+ progenitor cells after granulocyte colony
      stimulating factor-induced differentiation. In both models of granulocytic
      differentiation, we observed significant HIC1 induction. When HIC1 mRNA was
      suppressed in HL-60 cells using stably expressed short hairpin RNA targeting
      HIC1, granulocytic differentiation was altered as assessed by CD11b expression.
      Bisulphite sequencing of GC-rich regions (CpG islands) in the HIC1 promoter
      provided evidence that the observed suppression in HL-60 cells was not because of
      promoter hypermethylation. Our findings indicate a role for the tumour suppressor
      gene HIC1 in granulocytic differentiation. Low expression of HIC1 may very well
      contribute to pathogenic events in leukaemogenesis.

PMID- 18318773
TI  - Safety, tolerability and pharmacokinetics of udenafil, a novel PDE-5 inhibitor,
      in healthy young Korean subjects.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: The phosphodiesterase (PDE) type 5
      inhibitor is a widely used agent that facilitates penile erection. Udenafil is
      newly developed as a PDE-5 inhibitor. WHAT THIS STUDY ADDS: This is the first
      study to determine the safety, tolerability and pharmacokinetics of udenafil in
      healthy subjects. Udenafil was safe and well tolerated in healthy Korean
      subjects. The AUC and C(max) of udenafil increased supraproportionally with
      increasing dose upon single administration, but there was no significant drug
      accumulation upon multiple administrations. AIM: To evaluate the safety,
      tolerability and pharmacokinetics (PK) of udenafil, a novel phosphodiesterase
      type 5 inhibitor. METHODS: A double-blind, randomized, placebo-controlled, dose
      rising, parallel-group, single- and multiple-dose study was conducted in healthy
      Korean subjects. The subjects were allocated to single-dose groups of 25, 50,
      100, 200 or 300 mg (eight subjects in each dose group, including two placebos),
      or to multiple-dose groups of 100 or 200 mg (once-daily dosing for 7 days; nine
      subjects in each dose group, including three placebos). Serial samples of blood
      and urine were collected after oral administration and the drug concentrations in
      plasma and urine were determined by high-performance liquid chromatography.
      Safety and tolerability were evaluated by monitoring clinical laboratory
      parameters and adverse events. RESULTS: Udenafil reached peak plasma
      concentrations at 0.8-1.3 h, and then declined mono-exponentially with a terminal
      half-life of 7.3-12.1 h in the single-dose study. The area under the time
      concentration curves (AUC) and maximum plasma concentrations (C(max)) increased
      supraproportionally with increasing dose in the single-dose study. During
      multiple dosing, a steady state was reached at 5 days and little accumulation
      occurred after repeated dosing for 7 days. Udenafil was generally well tolerated
      in these healthy subjects, and no serious adverse events occurred. CONCLUSIONS:
      Udenafil was safe and well tolerated in healthy volunteers. The AUC and C(max) of
      udenafil increased supraproportionally with increasing dose upon single
      administration, but there was no significant drug accumulation upon multiple
      administrations.

PMID- 18318774
TI  - UGT1A6 genotype-related pharmacokinetics of deferiprone (L1) in healthy
      volunteers.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: UGT1A6 has been proposed as the
      predominant isoform responsible for the glucuronidation of deferiprone. UGT1A6*2
      allele has been associated with the altered enzyme activity. WHAT THIS STUDY
      ADDS: There is no statistically significant effect of UGT1A6 genotype on the
      single-dose pharmacokinetics of deferiprone in healthy volunteers. Gender
      influences serum pharmacokinetics of deferiprone. Body iron stores reflected by
      serum ferritin levels may have an influence on the extent of extravascular
      deferiprone distribution. AIMS To examine the effects of UGT1A6 polymorphisms on
      the pharmacokinetics of deferiprone in healthy volunteers. METHODS: Twenty-two
      healthy volunteers were enrolled and grouped according to UGT1A6 genotype. After
      an overnight fast, the subjects received a single oral dose of 25 mg kg(-1)
      deferiprone. Blood samples were collected at 0, 15, 30, 45, 60, 90, 120, 180,
      240, 300 and 360 min after dosing. Urine output was collected at 0, 0-2, 2-4, 4
      8, 8-12 and 12-24 h. Deferiprone (L1) and deferiprone-glucuronide (L1G)
      concentrations in serum and urine were determined using a validated high
      performance liquid chromatography method. UGT1A6 genotypes were determined by
      polymerase chain reaction-restriction fragment length polymorphism analysis.
      RESULTS: No statistically significant differences in any pharmacokinetic
      parameters of either deferiprone or deferiprone-glucuronide among the genotype
      groups were noted. Likewise, there were no statistically significant differences
      in 24-h urinary deferiprone and deferiprone-glucuronide excretion among the
      genotype groups. Significant differences between men and women were found in
      AUC(0-infinity), V(d)/F, and CL/F of deferiprone. Gender differences in 24-h
      urinary deferiprone and its metabolite excretion, however, failed to reach
      statistical significance. The V(d)/F of deferiprone was found to correlate
      significantly with serum ferritin (r(s) = 0.665; P = 0.001). CONCLUSION: The
      studied single nucleotide polymorphisms in UGT1A6 do not appear to exert
      statistically significant effects on the single-dose pharmacokinetics of
      deferiprone. Gender appears to influence the serum pharmacokinetics of
      deferiprone, but not urinary excretion of deferiprone and its metabolite. Body
      iron stores may have an influence on the extent of extravascular deferiprone
      distribution.

PMID- 18318775
TI  - Survival after lung transplantation of cystic fibrosis patients infected with
      Burkholderia cepacia complex.
AB  - Within the Burkholderia cepacia complex (Bcc), B. cenocepacia portends increased
      mortality compared with other species. We investigated the impact of Bcc
      infection on mortality and re-infection following lung transplant (LT). Species
      designation for isolates from Bcc-infected patients was determined using 16S rDNA
      and recA gene analyses. Of 75 cystic fibrosis patients undergoing LT from
      September 1992 to August 2002, 59 had no Bcc and 16 had Bcc (including 7 B.
      cenocepacia) isolated in the year before LT. Of the latter, 87.5% had Bcc
      recovered after transplantation, and all retained their pretransplant strains.
      Survival was 97%, 92%, 76% and 63% for noninfected patients; 89%, 89%, 67% and
      56% for patients infected with Bcc species other than B. cenocepacia; and 71%,
      29%, 29% and 29% for patients with B. cenocepacia (p = 0.014) at 1 month, 1 year,
      3 years and 5 years, respectively. Patients infected with B. cenocepacia before
      transplant were six times more likely to die within 1 year of transplant than
      those infected with other Bcc species (p = 0.04) and eight times than noninfected
      patients (p < 0.00005). Following LT, infection with Bcc species other than B.
      cenocepacia does not significantly impact 5-year survival whereas infection with
      B. cenocepacia pretransplant is associated with decreased survival.

PMID- 18318776
TI  - Early events in kidney donation: progression of endothelial activation, oxidative
      stress and tubular injury after brain death.
AB  - Cerebral injury leading to brain death (BD) causes major physiologic derangements
      in potential organ donors, which may result in vascular-endothelial activation
      and affect posttransplant graft function. We investigated the kinetic of pro
      coagulatory and pro-inflammatory endothelial activation and the subsequent
      oxidative stress and renal tubular injury, early after BD declaration. BD was
      induced by slowly inflating a balloon-catheter inserted in the extradural space
      over a period of 30 min. Rats (n = 30) were sacrificed 0.5, 1, 2 or 4 h after BD
      induction and compared with sham-controls. This study demonstrates immediate pro
      coagulatory and pro-inflammatory activation of vascular endothelium after BD in
      kidney donor rats, proportional with the duration of BD. E- and P-Selectins,
      Aalpha/Bbeta-fibrinogen mRNA were abruptly and progressively up-regulated from
      0.5 h BD onwards; P-Selectin membrane protein expression was increased;
      fibrinogen was primarily visualized in the peritubular capillaries. Plasma von
      Willebrand factor was significantly higher after 2 h and 4 h BD. Urine heart
      fatty-acid-binding-protein and N-acetyl-glucosaminidase, used as new specific and
      sensitive markers of proximal and distal tubular damage, were found significantly
      increased after 0.5 h, with a maximum at 4 h. Unexpectedly, oxidative stress was
      detectable only late, after the installation of tubular injury, suggesting only a
      secondary role for hypoxia in triggering these injuries.

PMID- 18318777
TI  - Gadolinium exposure in organ donors may cause nephrogenic system fibrosis in
      transplant recipients never exposed to gadolinium.

PMID- 18318778
TI  - The cardiac allograft is going up in smoke: a call to action.

PMID- 18318779
TI  - Heart transplantation for homozygous familial transthyretin (TTR) V122I cardiac
      amyloidosis.
AB  - Heart failure is the usual cause of death in patients with amyloid
      cardiomyopathy. The commonest form of hereditary cardiac amyloidosis is
      associated with the Val122Ile variant of transthyretin (TTR), which is carried by
      3-4% of the African American population. Here, we report the outcome of the first
      cardiac transplantation in a patient with TTR V122I. A 59-year-old Caribbean man
      presented with biventricular failure. Other than previous bilateral carpel tunnel
      syndrome, he had been well and had no evidence of extracardiac amyloidosis. An
      endomyocardial biopsy demonstrated amyloid of TTR type. Sequencing of TTR gene
      indicated homozygosity for V122I. He underwent cardiac transplantation and 3
      years later, remains well with no evidence of allograft or systemic amyloid
      deposition.

PMID- 18318780
TI  - The oversight of solid organ transplantation in the United States.
AB  - The publication of the Organ Procurement and Transplantation Network (OPTN) Final
      Rule in 2000 resulted in a new and different regulatory environment for solid
      organ transplantation in the United States. In this review the role of the OPTN
      in providing oversight is clarified, differentiating the powers of enforcement
      the OPTN and HHS possess compared to the importance of confidential peer review
      in promoting compliance with OPTN policies. The function of the OPTN's Membership
      and Professional Standards Committee (MPSC) in adjudicating center performance
      and investigating alleged violations is described as well as the type and impact
      of adverse actions that the MPSC can recommend. The role of the OPTN Board
      compared to that of the Secretary of HHS in determining adverse actions is
      differentiated. We describe MPSC's broad scope of work in the ongoing evaluation
      of performance of all transplant centers. Finally, the relationship between the
      OPTN oversight and other entities charged with safe health care practices in the
      United States is considered.

PMID- 18318781
TI  - Last resort for renal transplant recipients, 'restored kidneys' from living
      donors/patients.
AB  - Because of the grave shortage of deceased kidney allografts in Japan, we have
      embarked on a new source of organs, 'Restored kidneys' from living patients. From
      January 1991 through September 2006, 42 kidneys (eight benign pathology, eight
      small renal cancers, eight ureteral cancers, six aneurysms, eight severe
      nephrotic syndrome from four patients and four ureteral stenosis) were obtained
      from 38 patients/donors after extensive discussion of treatment modalities and
      risks. All patients/donors agreed to undergo total nephrectomy. The lesions were
      removed/repaired ex vivo on the back table, then transplanted. All recipients
      were notified of all possible risks including donor disease recurrence. One, 5
      and 10-year patient survival rates of restored transplant patients were 92.9%,
      79.3% and 63.8%, respectively. One, 5 and 10-year graft survival rates of
      restored kidney transplant patients were 78.6%, 51.8% and 42.7%, respectively.
      There were no recurrences of small renal cell carcinomas. There was one
      recurrence of ureteral cancer in the transplanted kidney 15 months after
      operation. In countries where deceased donors are scarce, such as Japan, the
      restored kidneys can be a last resort for renal allografts.

PMID- 18318782
TI  - Larger dose of intradermal influenza vaccination may be more immunogenic in
      transplant recipients.

PMID- 18318783
TI  - A novel model measuring the harm of transplanting hepatocellular carcinoma
      exceeding Milan criteria.
AB  - No empirical studies have defined the posttransplant survival that would justify
      expansion of the Milan criteria for liver transplantation of hepatocellular
      carcinoma. We created a Markov model comparing the survival benefit of
      transplantation for a patient with >Milan HCC, versus the harm caused to other
      patients on the waiting list. In the base-case analysis, the strategy of
      transplanting the patient with >Milan HCC resulted in a 44% increased risk of
      death and a utility loss of 3 quality-adjusted years of life across the pre- and
      posttransplant periods for a nationally representative cohort of patients on the
      waiting list. This harm outweighed the benefit of transplantation for a patient
      with >Milan HCC having a 5-year posttransplant survival of less than 61%. This
      survival threshold was most sensitive to geographic variations in organ shortage,
      with the threshold varying from 25% (Region 3) to >72% (Regions 1, 5, 7 and 9).
      In conclusion, expansion of the Milan criteria will require demonstrating high
      survival rates for the newly eligible patients-approximately 61% at 5 years after
      transplantation. In regions with less severe organ shortage, a more aggressive
      approach to transplanting these patients may be justified.

PMID- 18318784
TI  - Pharmacokinetics and pharmacodynamics of cinacalcet in patients with
      hyperparathyroidism after renal transplantation.
AB  - Cinacalcet is a calcimimetic drug for the treatment of secondary
      hyperparathyroidism (HPT). In a sequential open-label study, ten patients with
      persistent HPT after renal transplantation received first 30 and then 60 mg oral
      cinacalcet once daily over 2 weeks each. Cinacalcet steady state oral clearance
      was 131.1 +/- 20.9 l/h and 92.8 +/- 9.5 l/h (mean +/- SE) after 30 and 60 mg,
      respectively. Cinacalcet and parathyroid hormone (PTH) concentrations showed an
      inverse correlation and were fitted to a simple E(max) model (E(max) = 80%
      reduction vs. baseline, EC(50) = 13 ng/mL). A once daily administration of
      cinacalcet lowered serum calcium over 24 h without fluctuations. The 8-h
      fractional urinary excretion of calcium was increased after 60 mg cinacalcet
      (baseline 0.85 +/- 0.17%, 30 mg 1.53 +/- 0.35%, 60 mg 1.92 +/- 0.37%). Renal
      function remained stable. Cinacalcet pharmacokinetics and pharmacodynamics showed
      a pronounced interindividual variability. We conclude that the once daily
      administration of cinacalcet in patients with secondary HPT after renal
      transplantation effectively reduced iPTH and serum calcium. The transient
      calciuria could potentially favor nephrocalcinosis and reduce bone mineral
      density, suggesting that higher doses of cinacalcet need to be used with caution
      in renal transplant recipients with severe persistent hyperparathyroidism.

PMID- 18318785
TI  - Efficient approximation of P-value of the maximum of correlated tests, with
      applications to genome-wide association studies.
AB  - Genome-wide association study (GWAS), typically involving 100,000 to 500,000
      single-nucleotide polymorphisms (SNPs), is a powerful approach to identify
      disease susceptibility loci. In a GWAS, single-marker analysis, which tests one
      SNP at a time, is usually used as the first stage to screen SNPs across the
      genome in order to identify a small fraction of promising SNPs with relatively
      low p-values for further and more focused studies. For single-marker analysis,
      the trend test derived for an additive genetic model is often used. This may not
      be robust when the additive assumption is not appropriate for the true underlying
      disease model. A robust test, MAX, based on the maximum of three trend test
      statistics derived for recessive, additive, and dominant models, has been
      proposed recently for GWAS. But its p-value has to be evaluated through a
      resampling-based procedure, which is computationally challenging for the analysis
      of GWAS. Obtaining the p-value for MAX with adjustment for the covariates can be
      even more time-consuming. In this article, we provide a simple approximation for
      the p-value of the MAX test with or without adjusting for the covariates. The new
      method avoids resampling steps and thus makes the MAX test readily applicable to
      GWAS. We use simulation studies as well as real datasets on 17 confirmed disease
      associated SNPs to assess the accuracy of the proposed method. We also apply the
      method to the GWAS of coronary artery disease.

PMID- 18318786
TI  - Polymorphisms of the tumor suppressor gene LSAMP are associated with left main
      coronary artery disease.
AB  - Previous association mapping on chromosome 3q13-21 detected evidence for
      association at the limbic system-associated membrane protein (LSAMP) gene in
      individuals with late-onset coronary artery disease (CAD). LSAMP has never been
      implicated in the pathogenesis of CAD. We sought to thoroughly characterize the
      association and the gene. Non-redundant single nucleotide polymorphisms (SNPs)
      across the gene were examined in an initial dataset (168 cases with late-onset
      CAD, 149 controls). Stratification analysis on left main CAD (N = 102) revealed
      stronger association, which was further validated in a validation dataset (141
      cases with left main CAD, 215 controls), a third control dataset (N = 255), and a
      family-based dataset (N = 2954). A haplotype residing in a novel alternative
      transcript of the LSAMP gene was significant in all independent case-control
      datasets (p = 0.0001 to 0.0205) and highly significant in the joint analysis (p =
      0.00004). Lower expression of the novel alternative transcript was associated
      with the risk haplotype (p = 0.0002) and atherosclerosis burden in human aortas
      (p = 0.0001). Furthermore, silencing LSAMP expression in human aortic smooth
      muscle cells (SMCs) substantially augmented SMC proliferation (p<0.01).
      Therefore, the risk conferred by the LSAMP haplotype appears to be mediated by
      LSAMP down-regulation, which may promote SMC proliferation in the arterial wall
      and progression of atherosclerosis.

PMID- 18318787
TI  - Alternative splicing at exon 28 of the acetyl-coenzyme A carboxylase alpha gene
      in adult pigs and embryos.

PMID- 18318788
TI  - Characterization of the porcine KIT ligand gene: expression analysis, genomic
      structure, polymorphism detection and association with coat colour traits.
AB  - Kit ligand (KITLG) is the ligand for the type III receptor tyrosine kinase KIT.
      Studies of the KIT/KITLG pathway in a number of mammalian species have shown that
      it is important for the development of stem cell populations in haematopoietic
      tissues, germ cells in reproductive organs and the embryonic migrating
      melanoblasts that give rise to melanocytes. Consequently, mutations in the
      pathway may result in a range of defects including anaemia, sterility and de
      pigmentation. The cDNA sequence of the porcine KITLG gene has been reported
      previously, and is an attractive candidate locus for moderating coat colour in
      pigs. In this paper we report the gene structure and physical mapping of the
      porcine gene. We also report the identification of polymorphisms in the gene, one
      of which was used to confirm linkage to chromosome 5. Preliminary RNA expression
      studies using a panel of tissues have shown that in addition to the known variant
      lacking exon 6, there is alternative splicing of exon 4. However, little evidence
      was found for the KITLG gene being linked to variation in colour in a Meishan x
      Large White cross.

PMID- 18318789
TI  - Identification of polymorphisms influencing feed intake and efficiency in beef
      cattle.
AB  - Feed efficiency is an economically important trait in beef cattle. Net feed
      efficiency, measured as residual feed intake (RFI), is the difference between
      actual feed intake and the predicted feed intake required for maintenance and
      gain of the animal. SNPs that show associations with RFI may be useful
      quantitative trait nucleotides for marker-assisted selection. This study
      identified associations between SNPs underlying five RFI QTL on five bovine
      chromosomes (BTA2, 5, 10, 20 and 29) with measures of dry matter intake (DMI),
      RFI and feed conversion ratio (FCR) in beef cattle. Six SNPs were found to have
      effects on RFI (P < 0.05). The largest single SNP allele substitution effect for
      RFI was -0.25 kg/day located on BTA2. The combined effects of the SNPs found
      significant in this experiment explained 6.9% of the phenotypic variation of RFI.
      Not all the RFI SNPs showed associations with DMI and FCR even though these
      traits are highly correlated with RFI (r = 0.77 and r = 0.62 respectively). This
      shows that these SNPs may be affecting the underlying biological mechanisms of
      feed efficiency beyond feed intake control and weight gain efficiency. These SNPs
      can be used in marker-assisted selection but first it will be important to verify
      these effects in independent populations of cattle.

PMID- 18318790
TI  - Application of the Sleeping Beauty transposon system to avian cells.
AB  - We have for the first time assessed the ability of the Sleeping Beauty (SB)
      transposon system to enhance transgenesis in chicken and turkey cells. The
      efficiency of transgenesis with a transposon encoding an antibiotic resistance
      gene was dramatically enhanced 15- to 35-fold when transposase was supplied by co
      transfection of immortalized chicken and turkey cells with a construct encoding
      SB. In contrast, transgenesis of primary chicken embryo fibroblast (CEF) cells
      was not significantly increased by providing transposase, suggesting that the
      benefits of transposon-transgenesis in primary avian cells will require the
      application of more efficient transfection methods, further enhanced SB
      transposase or an alternative transposon system.

PMID- 18318791
TI  - A genetic linkage map for coho salmon (Oncorhynchus kisutch).
AB  - Construction of genetic linkage maps is an important first step for a variety of
      genomic applications, such as selective breeding in aquaculture, comparative
      studies of chromosomal evolution and identification of loci that have played key
      roles in the evolution of a species. Here we present a sex-specific linkage map
      for coho salmon. The map was constructed using 148 AFLP markers, 133
      microsatellite loci and the phenotypic locus SEX. Twenty-four linkage groups
      spanning 287.4 cM were mapped in males, and 33 linkage groups spanning 429.7 cM
      were mapped in females. Several male linkage groups corresponded to two female
      linkage groups. The combination of linkage groups across both sexes appeared to
      characterize regions of 26 chromosomes. Two homeologous chromosomes were
      identified based on information from duplicated loci. Homologies between the coho
      and rainbow trout maps were examined. Eighty-six loci were found to form common
      linkage relationships between the two maps; these relationships provided evidence
      for whole-arm fissions, fusions and conservation of chromosomal regions in the
      evolution of these two species.

PMID- 18318792
TI  - Decision memo for percutaneous transluminal angioplasty of the carotid artery
      concurrent with stenting (CAG-00085R3).

PMID- 18318793
TI  - fMRI of optokinetic eye movements with and without a contribution of smooth
      pursuit.
AB  - BACKGROUND AND PURPOSE: Optokinetic eye movements are elicited when tracking a
      moving pattern. It can be argued that a moving pattern of stripes invokes both
      the optokinetic and the smooth pursuit eye movement system, which may confound
      the observed brain activation patterns using functional magnetic resonance
      imaging (fMRI). A moving pattern of limited-lifetime-dot stimulation does not
      target the smooth pursuit eye movement system. METHODS: fMRI was used to compare
      the cortical activity elicited by an optokinetic eye movement response evoked by
      a moving pattern of stripes and a moving pattern of limited lifetime dots.
      RESULTS: The eye movement behavior showed that both types of stimuli evoked an
      adequate and similar optokinetic eye movement response, but stimulation with
      stripes evoked more activation in the frontal and parietal eye fields, MT/V5, and
      in the cerebellar area VI than stimulation with limited-lifetime dots.
      CONCLUSIONS: These brain areas are implicated in smooth pursuit eye movements.
      Our results suggest that indeed both the optokinetic and the smooth pursuit eye
      movement system are involved in tracking a moving pattern of stripes.

PMID- 18318794
TI  - Normalized upper cervical spinal cord atrophy in multiple sclerosis.
AB  - BACKGROUND AND PURPOSE: To find an optimal normalizing factor for upper cervical
      spinal cord area (UCCA) and to establish whether, in a cross-sectional study, the
      normalized UCCA correlates better with the neurological disability than the
      absolute measurement in multiple sclerosis patients. METHODS: UCCA and three
      potential normalizing factors were estimated from magnetic resonance imaging data
      in 51 control subjects. Their reliability was assessed and the linear
      relationships between UCCA and three potential correction factors were
      investigated. UCCA was then normalized by these factors respectively. On the
      basis of these results, an optimal factor was selected and applied to 29 MS
      subjects. RESULTS: An extremely strong correlation between UCCA and LECA was seen
      (r= .88, P < .01). The coefficient of variation (COV) of UCCA was reduced to 4.4%
      from 9.3% after correction by LECA. The normalized measurement of UCCA correlated
      better with the expanded disability status scale (EDSS) than the absolute
      measurement especially in relapsing-remitting multiple sclerosis patients.
      Moreover, more spinal cord atrophy was identified in corrected data than
      uncorrected data. CONCLUSION: Our findings suggest that LECA is an optimal
      correction factor for UCCA and normalized UCCA is preferable to absolute
      measurement in cross-sectional study.

PMID- 18318795
TI  - Recovery of reversed basilar artery flow as seen by transcranial sonography and
      MRA source images for vertebral dissection.
AB  - The dissection of the intracranial vertebral artery (VAD) is a common cause of
      young age brain stem stroke. VAD can be detected by conventional angiography, but
      there is yet no agreement on the most effective tool to use for the detection of
      VAD. Here, we report a patient with VAD, who was diagnosed with an intimal flap
      within the left vertebral artery by the magnetic resonance angiography (MRA)
      source images. Transcranial Doppler (TCD) showed a reversed flow in the basilar
      artery. After 4 months, TCD and transcranial color-coded Doppler (TCCD) confirmed
      a normal anterograde flow of the vertebro-basilar arteries.

PMID- 18318798
TI  - Prevention vs. cure.

PMID- 18318799
TI  - Genesis of the prevention guidelines project.

PMID- 18318800
TI  - Guidelines for the prevention of venous ulcers.

PMID- 18318801
TI  - Guidelines for the prevention of pressure ulcers.

PMID- 18318802
TI  - Guidelines for the prevention of diabetic ulcers.

PMID- 18318803
TI  - Guidelines for the prevention of lower extremity arterial ulcers.

PMID- 18318804
TI  - Subepidermal moisture differentiates erythema and stage I pressure ulcers in
      nursing home residents.
AB  - The objective of this descriptive cohort study was to examine the relationship
      between subepidermal moisture (SEM) and visual assessment of early pressure
      ulcers (PUs) in 31 nursing home (NH) residents residing in two NHs. Concurrent
      visual assessments and SEM were obtained at the sacrum, right and left
      trochanters, buttocks, and ischium weekly for 20 weeks. Visual assessment was
      rated as normal, erythema, stage I PU, or stage II+ PU. SEM, measured with a
      dermal phase meter where higher readings indicate greater SEM (range: 0-999
      dermal phase units [DPU]), was modeled as a predictor of concurrent visual
      assessment of skin damage and erythema and stage I PUs at the sacrum 1 week later
      with covariate PU risk. Participants had a mean age of 84.1 years, were 83%
      female, 72% non-Hispanic white. SEM was lowest for normal skin (104 DPU, SD 114),
      higher for erythema (185 DPU, SD 138), stage I PUs (264 DPU, SD 208), and highest
      for stage II+ PUs (727 DPU, SD 287) across all sites (all p<0.01). SEM was
      responsive to visual assessment changes, differentiated between erythema and
      stage I PU, and higher SEM predicted greater likelihood of erythema/stage I PU at
      the sacrum the next week (odds ratio=1.32 for every 100 DPU increase, p=0.03).
      SEM was associated with concurrent skin damage and future (1 week later)
      development of sacral erythema/stage I PUs. SEM differentiates between erythema
      and stage I PUs. SEM may assist in predicting early PU damage, allowing for
      earlier intervention to prevent PUs.

PMID- 18318805
TI  - Use of a novel porcine collagen paste as a dermal substitute in full-thickness
      wounds.
AB  - A commercially available porcine collagen sheet material has been found
      previously to be useful as an implant for reconstructive surgery. However, its
      use as a dermal substitute has been hindered by slow cell penetration and
      vascularization. A novel paste formulation of this material was investigated for
      its potential role as a dermal substitute in full-thickness wounds. A porcine
      punch biopsy model was initially used to assess the integration of a wide range
      of material formulations. Selected formulations were then assessed further in a
      larger wound-chamber model. Paste formulations were compared with those of sheet
      and another commercially available dermal regeneration template. The porcine
      collagen paste became integrated into full-thickness wounds without rejection and
      without excessive inflammation. It was detected in wounds up to day 27
      postimplantation. Porcine collagen paste was readily infiltrated by host cells by
      day 2 and supported migrating keratinocytes on its surface. Staining for
      endothelial cells indicated neovasculature formation as early as day 4 and
      functional newly formed microvessels were noted at day 7. This was comparable
      with neovascularization of an alternative and clinically proven dermal
      regeneration template and was significantly superior to the sheet material
      formulation at the same time points. Our findings suggest that porcine collagen
      paste may be suitable as an alternative to current dermal substitutes in full
      thickness wounds.

PMID- 18318806
TI  - Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the
      genetically diabetic mouse.
AB  - Healing of diabetic wounds still remains a critical medical problem.
      Polydeoxyribonucleotide (PDRN), a compound having a mixture of
      deoxyribonucleotide polymers, stimulates the A2 purinergic receptor with no toxic
      or adverse effect. We studied the effects of PDRN in diabetes-related healing
      defect using an incisional skin-wound model produced on the back of female
      diabetic mice (db+/db+) and their normal littermates (db+/+m). Animals were
      treated daily for 12 days with PDRN (8 mg/kg/ip) or its vehicle (100 muL
      0.9%NaCl). Mice were killed 3, 6, and 12 days after skin injury to measure
      vascular endothelial growth factor (VEGF) mRNA expression and protein synthesis,
      to assay angiogenesis and tissue remodeling through histological evaluation, and
      to study CD31, Angiopoietin-1 and Transglutaminase-II. Furthermore, we measured
      wound breaking strength at day 12. PDRN injection in diabetic mice resulted in an
      increased VEGF message (vehicle=1.0+/-0.2 n-fold vs. beta-actin; PDRN=1.5+/-0.09
      n-fold vs. beta-actin) and protein wound content on day 6 (vehicle=0.3+/-0.07
      pg/wound; PDRN=0.9+/-0.1 pg/wound). PDRN injection improved the impaired wound
      healing and increased the wound-breaking strength in diabetic mice. PDRN also
      caused a marked increase in CD31 immunostaining and induced Transglutaminase-II
      and Angiopoietin-1 expression. Furthermore, the concomitant administration of 3,7
      dimethyl-1-propargilxanthine, a selective adenosine A2A receptor antagonist,
      abolished PDRN positive effects on healing. However, 3,7-dimethyl-1
      propargilxanthine alone did not affect wound healing in both diabetic mice and
      normal littermates. These results suggest that PDRN might be useful in wound
      disorders associated with diabetes.

PMID- 18318807
TI  - Healing modulation induced by freeze-dried platelet-rich plasma and micronized
      allogenic dermis in a diabetic wound model.
AB  - The incidence and prevalence of chronic and diabetic wounds are increasing and
      clinical treatments to tackle these epidemics are still insufficient. In this
      study, we tested the ability of freeze-dried platelet-rich plasma (PRP) and an
      allogenic micronized acellular dermal matrix alone and in combination to modulate
      diabetic wound healing. Therapeutic materials were applied to 1.0 cm(2)
      excisional wounds on genetically diabetic (db/db) mice. Wound-healing kinetics
      and new tissue formation were studied at 9 and 21 days posttreatment.
      Quantitative immunohistochemistry was used to study vascularity and cellular
      proliferation (days 9 and 21), and collagen deposition was evaluated 21 days
      postwounding. In vitro, micronized allogenic dermis, when combined with PRP,
      absorbed nearly 50% of original platelet-derived growth factor, transforming
      growth factor-beta, vascular endothelial growth factor, and epidermal growth
      factor from platelets and stimulated fibroblast proliferation. In vivo,
      micronized dermis increased the formation of vascularized wound tissue by day 9.
      Freeze-dried PRP alone or in combination with micronized dermis increased wound
      tissue revascularization and proliferation compared with spontaneous healing. The
      increase in cell proliferation persisted until day 21 only when freeze-dried PRP
      was used in combination with micronized dermis. These results indicate that
      micronized allogenic dermis may be used to provide a dermal matrix to stimulate
      tissue formation and the combination with PRP may confer additional beneficial
      growth factors to chronic or diabetic wounds.

PMID- 18318808
TI  - The mast cell stabilizer ketotifen prevents development of excessive skin wound
      contraction and fibrosis in red Duroc pigs.
AB  - Skin wound healing in Yorkshire pigs closely approximates human wound healing.
      Conversely, red Duroc pigs form fibroproliferative, hypercontractile scars. As
      mast cells have been implicated in several fibrotic conditions, the present study
      used these models to evaluate the potential role of mast cells in wound
      contraction and fibrosis. Immediately following the creation of full-thickness
      excisional wounds, the mast cell stabilizer ketotifen was used to treat both
      Yorkshire and red Durocs. Control red Durocs showed significantly more wound
      contraction than Yorkshires, both before and after reepithelialization. Ketotifen
      treatment significantly reduced the first phase of contraction in red Duroc
      wounds to a level equivalent to Yorkshire wounds, but had no detectable effect on
      the postepithelialization phase of contraction. Cessation of drug treatment after
      10 weeks did not lead to resumption of excessive contraction in red Durocs,
      indicating that ketotifen blocked rather than delayed such contraction during a
      critical phase of healing. Ketotifen treatment also reduced the deposition of
      collagen within the red Duroc wounds, but did not affect Yorkshire wound
      contraction or collagen deposition. These results suggest that ketotifen may be
      an effective treatment for the reduction of excessive wound contraction and
      fibrosis in human cutaneous injuries, without affecting the normal healing
      process.

PMID- 18318809
TI  - Correlation of near infrared absorption and diffuse reflectance spectroscopy
      scattering with tissue neovascularization and collagen concentration in a
      diabetic rat wound healing model.
AB  - The objective of this paper was to correlate optical changes of tissue during
      wound healing measured by near infrared (NIR) and diffuse reflectance
      spectroscopy (DRS) with histologic changes in an animal model. Amplitude and
      phase of scattered light were obtained in a diabetic rat and control model and
      biopsies were taken for blood vessel ingrowth and collagen concentration. NIR
      absorption coefficient correlated with blood vessel ingrowth over time, in both
      the control and diabetic animals. DRS data correlated with collagen
      concentration. Previous publications by this group documented only the NIR
      changes during the wound healing process but this is the first reported
      correlation with histology data. The ability to correlate DRS scattering with
      collagen concentration during healing is another important and novel finding.
      This technology may play an important role clinically in assessing the efficacy
      of wound healing agents in diabetics.

PMID- 18318810
TI  - Differing responses of human follicular and nonfollicular scalp cells in an in
      vitro wound healing assay: effects of estrogen on vascular endothelial growth
      factor secretion.
AB  - Improved wound healing of hairy skin may involve mesenchymal hair follicle cells
      with stem cell potential and enhancement by estrogen therapy. How estrogen
      affects follicular dermal papilla (DP) and dermal sheath (DS) cells in wound
      healing is unknown. Therefore, a comparison of estradiol action on DP, DS, and
      corresponding interfollicular dermal fibroblasts (DF) in a scratch-wound assay
      was performed using matching primary cultures established from female temporo
      occipital scalp. All three cell types expressed mRNA transcripts and protein for
      estrogen receptors alpha (ERalpha) and beta (ERbeta). DF ERalpha transcripts were
      half that of DP and one-third of DS cells, while DF ERbeta transcripts were two
      thirds of DP and DS cells. In the scratch-wound assay all three cells types
      migrated at similar rates, but only the rate of DF was enhanced by estradiol.
      Mechanical wounding increased DNA synthesis rates of all three cell types and
      increased the secretion of collagen by DF and DS cells. All three secreted
      similar basal levels of vascular endothelial growth factor (VEGF), which was
      increased by wounding DF and DS cells, but not DP cells. DP cells required
      estradiol to increase VEGF secretion; by contrast VEGF secretion was decreased by
      estradiol in wounded DS cells. These results highlight differences in the
      responses of DF, DP, and DS cells to estradiol in a scratch-wound assay,
      providing further support for the dichotomy of cellular functions in the hair
      follicle. Further understanding of the role of estrogen in cutaneous wound
      healing may have important implications for the management of chronic wounds and
      scarring.

PMID- 18318811
TI  - Serum amyloid P inhibits dermal wound healing.
AB  - The repair of open wounds depends on granulation tissue formation and
      contraction, which is primarily mediated by myofibroblasts. A subset of
      myofibroblasts originates from bone-marrow-derived monocytes which differentiate
      into fibroblast-like cells called fibrocytes. Serum amyloid P (SAP) inhibits
      differentiation of monocytes into fibrocytes. Thus, we hypothesized that the
      addition of exogenous SAP would hinder the normal wound healing process.
      Excisional murine dorsal wounds were either injected with SAP (intradermal group)
      or the mice were treated with systemic SAP (intraperitoneal group) and compared
      with animals treated with vehicle. Grossly, SAP-treated wounds closed slower than
      respective controls in both groups. Histologically, the contraction rate was
      slower in SAP-treated wounds in both groups and the reepithelialization rate was
      slower in the intraperitoneal group. Furthermore, significantly less
      myofibroblasts expressing alpha-smooth muscle actin were noted in the
      intraperitoneal group wounds compared with controls. These data suggest that SAP
      delays normal murine dermal wound healing, probably due to increased inhibition
      of fibrocyte differentiation, and ultimately a decreased wound myofibroblast
      population. SAP may provide a potential therapeutic target to prevent or limit
      excessive fibrosis associated with keloid or hypertrophic scar formation.
      Furthermore, SAP removal from wound fluid could potentially accelerate the
      healing of chronic, nonhealing wounds.

PMID- 18318812
TI  - Impaired wound healing in an acute diabetic pig model and the effects of local
      hyperglycemia.
AB  - Diabetic wounds result in significant morbidity, prolonged hospitalization, and
      enormous health-care expenses. Pigs have been shown to have wound healing
      resembling that in humans. The aim of this study was to develop a large-animal
      model for diabetic wound healing. Diabetes was induced by streptozotocin
      injection in Yorkshire pigs. Full-thickness wounds were created and dressed with
      a sealed chamber. Nondiabetic pigs with or without high glucose wound fluid
      concentration served as controls. Glucose concentration in serum and wound fluid
      was measured and collected. Wound contraction was monitored, and biopsies were
      obtained for measurement of reepithelialization. Wound fluid was analyzed for
      insulin-like growth factor-1 (IGF-1), platelet-derived growth factor, and
      transforming growth factor. Glucose concentration in wound fluid initially
      followed serum levels and then decreased to undetectable on day 9.
      Reepithelialization was significantly delayed in diabetic pigs. In nondiabetic
      pigs, wounds treated in a local hyperglycemic environment, and thus excluding the
      effects of systemic hyperglycemia, showed no difference in wound closure compared
      with controls. This suggests that delayed wound healing in diabetes is not
      induced by local high-glucose concentration itself. Analysis of growth factor
      expression showed a marked reduction in IGF-1 in the diabetic wounds. Diabetic
      pigs have impaired healing that is accompanied by a reduction of IGF-1 in the
      healing wound and is not due to the local hyperglycemia condition itself.

PMID- 18318813
TI  - RGTA OTR 4120, a heparan sulfate proteoglycan mimetic, increases wound breaking
      strength and vasodilatory capability in healing rat full-thickness excisional
      wounds.
AB  - ReGeneraTing Agents (RGTAs), a family of polymers engineered to protect and
      stabilize heparin-binding growth factors, have been shown to promote tissue
      repair and regeneration. In this study, the effects of one of these polymers,
      RGTA OTR4120, on healing of full-thickness excisional wounds in rats were
      investigated. Two 1.5 cm diameter circular full-thickness excisional wounds were
      created on the dorsum of a rat. After creation of the wounds, RGTA OTR4120 was
      applied. The progress of healing was assessed quantitatively by evaluating the
      wound closure rate, vasodilatory capability, and wound breaking strength. The
      results showed a triple increase of the local vascular response to heat
      provocation in the RGTA OTR4120-treated wounds as compared with vehicle-treated
      wounds. On days 14 and 79 after surgery, the wounds treated with RGTA OTR4120
      gained skin strength 12% and 48% of the unwounded skin, respectively, and
      displayed a significantly increased gain in skin strength when compared with
      control animals. These results raise the possibility of efficacy of RGTA OTR4120
      in accelerating surgically cutaneous wound healing by enhancing the wound
      breaking strength and improving the microcirculation.

PMID- 18318814
TI  - Human dermal fibroblast subpopulations; differential interactions with vascular
      endothelial cells in coculture: nonsoluble factors in the extracellular matrix
      influence interactions.
AB  - The superficial dermis of adult human skin contains a complex arcading
      microvasculature that provides nutrient support to the overlying epidermis. We
      propose that the unique subpopulations of dermal fibroblasts located in the
      superficial dermis contribute to the organization and maintenance of this
      elaborate microvasculature. This possibility was tested in a coculture system in
      which distinct subpopulations of adult human dermal fibroblasts were grown to
      form high-density lawns that were then seeded with human umbilical vein vascular
      endothelial cells (EC). The fibroblast subpopulation cultured specifically from
      the papillary dermis supported a robust array of highly branched tube-like
      structures. In contrast, fibroblasts cultured from the reticular dermis provided
      an anemic level of support for the formation of tube-like structures. These
      varied interactions with vascular EC were not due to the differential production
      of the potent pro-angiogenic factors vascular endothelial growth factor-A or
      fibroblast growth factor-2. Instead, the extracellular matrix and/or molecules
      bound to this matrix appeared to contain instructions that modulated these
      differential fibroblast-vascular EC interactions. One matrix-binding growth
      factor, hepatocyte growth factor/scatter factor, was identified that was both
      differentially expressed by papillary and reticular dermal fibroblasts and which
      was shown to be physiologically relevant in the coculture model. These studies
      highlight the importance of fibroblasts in supporting and maintaining vascular
      integrity. Furthermore, these studies have important implications for wound
      repair and may help to explain how fibroblasts contribute to the etiology of
      nonhealing wounds.

PMID- 18318815
TI  - Altered tissue repair in hevin-null mice: inhibition of fibroblast migration by a
      matricellular SPARC homolog.
AB  - Matricellular proteins such as hevin, secreted protein acidic and rich in
      cysteine, and thrombospondin-2 play an important role during tissue repair
      through their influence on fundamental cellular activities such as adhesion,
      migration, proliferation, and extracellular matrix synthesis/reorganization. We
      have investigated the role played by hevin during excisional and incisional
      cutaneous wound repair in hevin-null mice. Hevin-null animals both close and heal
      their skin wounds faster than wild-type animals, as evidenced by enhanced
      macrophage infiltration of wound beds at early time points, the earlier
      appearance of mature extracellular matrix, and the overall higher maturity score.
      In addition, fibrovascular invasion of polyvinyl alcohol sponges was more robust
      in hevin-null mice, a result indicating that differences in cell migration might
      underlie the observed alterations in wound repair. Experiments in vitro showed
      that hevin induced the deadhesion and inhibited the migration of primary dermal
      fibroblasts in a Rac-1-dependent manner. These findings indicate that the
      differences in wound repair between hevin-null and wild-type animals can be
      attributed in part to the deadhesive function of hevin and reduced cell migration
      within dermal wound beds in which this protein is expressed.

PMID- 18318816
TI  - Publications from China: the sleeping giant awakens.

PMID- 18318817
TI  - Heparanase and gallbladder cancer: new insights into understanding tumor growth
      and invasion.

PMID- 18318818
TI  - Protocol-based management strategy for post-endoscopic retrograde
      cholangiopancreatography pancreatitis: can it make a difference?

PMID- 18318819
TI  - Core promoter mutations of hepatitis B virus and hepatocellular carcinoma: story
      beyond A1762T/G1764A mutations.

PMID- 18318821
TI  - Hepatotoxic slimming aids and other herbal hepatotoxins.
AB  - Perceptions of safety and/or cultural mores prompt individuals to seek herbal
      slimming aids in preference to conventional dietary, physical activity and
      medication-based protocols. In recent years, terpenoid-containing dietary
      supplements have been implicated in causing severe and sometimes fatal
      hepatotoxicity. Teucrium polium (germander) was the first of these herbal
      products to be clearly linked to cases of acute liver failure. Subsequently,
      similar hepatotoxicity has been observed with other members of the Teucrium
      genus. While diterpenoid-derived reactive metabolites are central to germander
      hepatotoxicity, it may also be that the hepatic effects of compounds such as Sho
      saiko-to, Centella asiatica and Black cohosh are linked to their triterpenoid
      content. Other non-terpenoid-containing herbal remedies marketed for weight
      reduction have been causally associated with significant liver injury. Important
      among these are preparations containing N-nitrosofenfluramine, usnic acid and
      ephedra alkaloids. Finally, we review recent data on known and emerging
      hepatotoxins such as Boh-Gol-Zhee, Kava, pyrrolizidine alkaloids and Shou-Wu
      Pian. Better public and physician awareness through health education, early
      recognition and management of herbal toxicity and tighter regulation of
      complementary/alternative medicine systems are required to minimize the dangers
      of herbal product use.

PMID- 18318820
TI  - Asia-Pacific consensus guidelines on gastric cancer prevention.
AB  - BACKGROUND AND AIM: Gastric cancer is a major health burden in the Asia-Pacific
      region but consensus on prevention strategies has been lacking. We aimed to
      critically evaluate strategies for preventing gastric cancer. METHODS: A
      multidisciplinary group developed consensus statements using a Delphi approach.
      Relevant data were presented, and the quality of evidence, strength of
      recommendation, and level of consensus were graded. RESULTS: Helicobacter pylori
      infection is a necessary but not sufficient causal factor for non-cardia gastric
      adenocarcinoma. A high intake of salt is strongly associated with gastric cancer.
      Fresh fruits and vegetables are protective but the use of vitamins and other
      dietary supplements does not prevent gastric cancer. Host-bacterial interaction
      in H. pylori infection results in different patterns of gastritis and differences
      in gastric acid secretion which determine disease outcome. A positive family
      history of gastric cancer is an important risk factor. Low serum pepsinogens
      reflect gastric atrophy and may be useful as a marker to identify populations at
      high risk for gastric cancer. H. pylori screening and treatment is a recommended
      gastric cancer risk reduction strategy in high-risk populations. H. pylori
      screening and treatment is most effective before atrophic gastritis has
      developed. It does not exclude the existing practice of gastric cancer
      surveillance in high-risk populations. In populations at low risk for gastric
      cancer, H. pylori screening is not recommended. First-line treatment of H. pylori
      infection should be in accordance with national treatment guidelines. CONCLUSION:
      A strategy of H. pylori screening and eradication in high-risk populations will
      probably reduce gastric cancer incidence, and based on current evidence is
      recommended by consensus.

PMID- 18318822
TI  - Scientific publications in gastroenterology and hepatology journals from Chinese
      authors in various parts of North Asia: 10-year survey of literature.
AB  - BACKGROUND AND AIMS: People of Chinese ethnicity are one of the groups at most
      risk of gastrointestinal and liver diseases in the world. The research status in
      gastroenterology and hepatology (gastrointestinal [GI]) among Chinese individuals
      in the three major regions of China-the mainland (ML), Hong Kong (HK), and Taiwan
      (TW)-are unknown. The outputs of articles published in international GI journals
      from the three regions were compared in this study. METHODS: Articles published
      in 52 journals related to GI originating from the ML, TW, and HK from1996-2005
      were retrieved from the PubMed database. The numbers of total articles, clinical
      trials, randomized controlled trials, case reports, impact factors (IF), citation
      reports, and articles published in the top general medical journals were
      conducted for quantity and quality comparisons. RESULTS: The number of articles
      from the three regions increased significantly from 1996 to 2005. There were 5170
      articles from the ML (2969), TW (1551), and HK (650). However, nearly 90% of
      articles from the ML were published in World Journal of Gastroenterology (WJG), a
      controversial Chinese journal. Following the exclusion of WJG, the ML had
      published the least number of articles and had the least total citations. The
      accumulated IF of the articles from TW (3747.893) was much higher than the ML
      (775.084) and HK (2272.972). HK had the highest average IF of articles in GI
      journals and the most articles published in the top, general medical journals
      among the three regions. CONCLUSION: The difference between the number of GI
      research articles published in the ML, TW, and HK still appears to be
      considerable, particularly when assessed by IF, although the gap appears to be
      narrowing.

PMID- 18318823
TI  - Protocol-based medical management of post-ERCP pancreatitis.
AB  - BACKGROUND AND AIMS: Although numerous studies have evaluated outcomes pertaining
      to endoscopic retrograde cholangio-pancreatography (ERCP) complications, studies
      evaluating outcomes of management of post-ERCP pancreatitis are scant. This study
      evaluated the effectiveness of a standard treatment protocol in management of
      post-ERCP pancreatitis. METHODS: This is a retrospective study of consecutive
      patients managed for post-ERCP pancreatitis, using a standard treatment protocol
      over a 3-year period. By protocol, patients received only intravenous fluids,
      narcotics, and analgesics for the first 24-72 h after admission. Oral intake was
      attempted when white cell count was normal or followed a downward trend,
      abdominal pain was absent or minimal without need for narcotics over a 12-h
      period, and serum lipase was less than three times normal range. For patients
      hospitalized beyond 72 h, an abdomen CT was obtained at days 4 and 10 to guide
      management. Intravenous antibiotics were administered only for patients with
      pancreatic necrosis. Jejunal feeding and a meperidine pump for pain control were
      initiated in symptomatic patients at day 4. Data on ERCP complications were
      collected prospectively and graded per consensus criteria. Effectiveness of the
      treatment protocol was evaluated by comparing clinical outcomes of patients
      managed by protocol versus those managed outside protocol. RESULTS: 45 of 1976
      patients (2.3%) who underwent ERCP developed post-ERCP pancreatitis. Of the 45
      (female 31; mean age 43 years) patients, 32 were managed by protocol and 13
      outside protocol. Protocol based management was associated with less severe
      disease as compared with those managed outside protocol (crude odds ratio (OR) =
      11.2; 95% confidence interval (CI) = 1.9-68.7; P = 0.002). One patient managed
      outside protocol died of severe pancreatitis. When compared with those managed
      outside protocol, the median duration of hospital stay (7 vs 3 days; P = 0.01),
      the use of CT (100% vs 15.6%; P < 0.001), and the use of antibiotics (50% vs
      3.1%; P = 0.01) were significantly lower in those managed by protocol. By
      multiple logistic regression, protocol-based management was associated with less
      severe disease (adjusted OR = 18.7; 95% CI = 2.6-132.1; P = 0.003) when adjusted
      for age, comorbidity, endotherapy and pancreatic stenting. CONCLUSIONS: A
      protocol-based management strategy was associated with less severe pancreatitis,
      shorter length of hospital stay, need for fewer imaging studies, and use of
      antibiotics. Prospective validation of these findings is justified.

PMID- 18318824
TI  - Endoluminal gastroplication for the treatment of gastroesophageal reflux disease:
      a 2-year prospective pilot study from Taiwan.
AB  - BACKGROUND AND AIM: Endoluminal gastroplication (ELGP) offers a minimally
      invasive option for the treatment of gastroesophageal reflux disease (GERD) in
      Western countries. However, long-term outcomes of ELGP in Asian populations have
      not been investigated. The aim of this prospective study was to evaluate the long
      term benefits of ELGP in Asian patients with GERD. METHODS: Taiwanese patients
      diagnosed with GERD were enrolled and had the procedure performed with EndoCinch.
      The assessment included symptom scoring, validated GERD questionnaires,
      esophagogastroduodenoscopy, esophageal manometry and 24-h pH monitoring before
      and after the procedure over a 2-year period. RESULTS: Twenty-one consecutive
      patients were recruited and underwent ELGP. Patients reported improved heartburn
      symptom score (mean 64.0 vs 21.1, P < 0.001), regurgitation frequency score (mean
      2.4 vs 1.3, P < 0.001), and GERD health-related quality of life (mean 23.1 vs
      10.1, P < 0.001) at 24 months. The mean total time of pH < 4 reduced from 121.7
      min to 67.1 min (P = 0.008) and mean DeMeester score reduced from 32.9 to 17.6 (P
      = 0.011) at 3 months. Antisecretory drug discontinuation rate was 81%, 57%, 52%
      and 48% at 1, 6, 12 and 24 months, respectively. Of the patients who had a
      favorable initial response to ELGP at 1 month, 41% resumed antisecretory
      medications at 24 months follow-up. All adverse events were mild and transient.
      CONCLUSIONS: Endoluminal gastroplication is a safe and modestly effective
      endotherapy for patients with GERD. It significantly improved symptoms in an
      Asian population. Approximately one in two patients continues to be off
      medication at 24 months follow-up. However, the long-term efficacy and durability
      are still to be determined.

PMID- 18318825
TI  - Virological and clinical implication of core promoter C1752/V1753 and T1764/G1766
      mutations in hepatitis B virus genotype D infection in Mongolia.
AB  - BACKGROUND AND AIM: The aim of the present study was to reveal virological and
      clinical features of hepatitis B virus (HBV) genotype D infection. METHODS: One
      hundred and twenty-two Mongolian chronic liver disease (CLD) patients infected
      with HBV were subjected for serological HBV-markers screening and HBV-enzyme
      immunoassay (EIA) genotyping. Nucleotide sequences were analyzed for 48 HBV/D
      strains (23 isolated from hepatocellular carcinoma (HCC) and 25 from CLD
      patients). RESULTS: Prevalence of hepatitis B e antigen (HBeAg) positivity was
      low (25.9%) in young patients (< or =30 years old) indicating early HBeAg
      seroclearance in HBV/D carriers. The T1764/G1766 double mutation was the most
      common basal core promoter (BCP) mutation (29.2%) and was frequent in HBeAg
      negative patients (39.3%). Patients harboring T1764/G1766 mutants exhibited lower
      HBV-DNA and HBV core antigen (HBcAg) levels than those with wild-type BCP strains
      (P = 0.024, 0.049, respectively). C1752 and/or V (not T) 1753 mutation was
      significantly prevalent in HCC patients (HCC vs CLD; 52.2% vs 20%, P = 0.033).
      T1762/A1764 mutation was detected in 75.0% of HCC patients with high viral load
      (> or =5 log copies/mL). Precore stop codon mutation A1896 was detected in
      (70.8%) of HBV/D-infected patients. CONCLUSIONS: In Mongolians infected with
      HBV/D, C1752 and/or V1753 mutation was associated with HCC.

PMID- 18318826
TI  - Education and imaging. Hepatobiliary and pancreatic: arteriovenous malformation
      of the pancreas.

PMID- 18318827
TI  - Education and imaging. Gastrointestinal: Chilaiditi syndrome.

PMID- 18318828
TI  - Education and imaging. Gastrointestinal: intramucosal gastric cancer treated by
      endoscopic submucosal dissection.

PMID- 18318832
TI  - Photosynthetic acclimation: molecular mechanisms of short and long-term
      acclimation.

PMID- 18318833
TI  - Photosynthetic acclimation: structural reorganisation of light harvesting antenna
      -role of redox-dependent phosphorylation of major and minor chlorophyll a/b
      binding proteins.
AB  - In order to carry out photosynthesis, plants and algae rely on the co-operative
      interaction of two photosystems: photosystem I and photosystem II. For maximum
      efficiency, each photosystem should absorb the same amount of light. To achieve
      this, plants and green algae have a mobile pool of chlorophyll a/b-binding
      proteins that can switch between being light-harvesting antenna for photosystem I
      or photosystem II, in order to maintain an optimal excitation balance. This
      switch, termed state transitions, involves the reversible phosphorylation of the
      mobile chlorophyll a/b-binding proteins, which is regulated by the redox state of
      the plastoquinone-mediating electron transfer between photosystem I and
      photosystem II. In this review, we will present the data supporting the function
      of redox-dependent phosphorylation of the major and minor chlorophyll a/b-binding
      proteins by the specific thylakoid-bound kinases (Stt7, STN7, TAKs) providing a
      molecular switch for the structural remodelling of the light-harvesting complexes
      during state transitions. We will also overview the latest X-ray crystallographic
      and electron microscopy-derived models for structural re-arrangement of the light
      harvesting antenna during State 1-to-State 2 transition, in which the minor
      chlorophyll a/b-binding protein, CP29, and the mobile light-harvesting complex II
      trimer detach from the light-harvesting complex II-photosystem II supercomplex
      and associate with the photosystem I core in the vicinity of the PsaH/L/O/P
      domain.

PMID- 18318834
TI  - Photosynthetic acclimation: does the dynamic structure and macro-organisation of
      photosystem II in higher plant grana membranes regulate light harvesting states?
AB  - The efficiency of light harvesting in higher plant photosynthesis is regulated in
      response to external environmental conditions. Under conditions of excess light,
      the normally highly efficient light-harvesting system of photosystem II is
      switched into a state in which unwanted, potentially harmful, energy is
      dissipated as heat. This process, known as nonphotochemical quenching, occurs by
      the creation of energy quenchers following conformational change in the light
      harvesting complexes, which is initiated by the build up of the thylakoid pH
      gradient and controlled by the xanthophyll cycle. In the present study, the
      evidence to support the notion that this regulatory mechanism is dependent upon
      the organization of the different antenna subunits in the stacked grana membranes
      is reviewed. We postulate that nonphotochemical quenching occurs within a
      structural locus comprising the PsbS subunit and components of the light
      harvesting antenna, CP26, CP24, CP29 and LHCIIb (the major trimeric light
      harvesting complex), formed in response to protonation and controlled by the
      xanthophyll cycle carotenoids.

PMID- 18318835
TI  - Photosynthetic acclimation: state transitions and adjustment of photosystem
      stoichiometry--functional relationships between short-term and long-term light
      quality acclimation in plants.
AB  - In dense plant populations, individuals shade each other resulting in a low-light
      habitat that is enriched in far-red light. This light quality gradient decreases
      the efficiency of the photosynthetic light reaction as a result of imbalanced
      excitation of the two photosystems. Plants counteract such conditions by
      performing acclimation reactions. Two major mechanisms are known to assure
      efficient photosynthesis: state transitions, which act on a short-term timescale;
      and a long-term response, which enables the plant to re-adjust photosystem
      stoichiometry in favour of the rate-limiting photosystem. Both processes start
      with the perception of the imbalanced photosystem excitation via
      reduction/oxidation (redox) signals from the photosynthetic electron transport
      chain. Recent data in Arabidopsis indicate that initialization of the molecular
      processes in both cases involve the activity of the thylakoid membrane-associated
      kinase, STN7. Thus, redox-controlled phosphorylation events may not only adjust
      photosystem antenna structure but may also affect plastid, as well as nuclear,
      gene expression. Both state transitions and the long-term response have been
      described mainly in molecular terms, while the physiological relevance concerning
      plant survival and reproduction has been poorly investigated. Recent studies have
      shed more light on this topic. Here, we give an overview on the long-term
      response, its physiological effects, possible mechanisms and its relationship to
      state transitions as well as to nonphotochemical quenching, another important
      short-term mechanism that mediates high-light acclimation. Special emphasis is
      given to the functional roles and potential interactions between the different
      light acclimation strategies. A working model displays the various responses as
      an integrated molecular system that helps plants to acclimate to the changing
      light environment.

PMID- 18318836
TI  - Cloning and functional characterization of Arabidopsis thaliana D-amino acid
      aminotransferase--D-aspartate behavior during germination.
AB  - The understanding of D-amino acid metabolism in higher plants lags far behind
      that in mammals, for which the biological functions of these unique amino acids
      have already been elucidated. In this article, we report on the biochemical
      behavior of D-amino acids (particularly D-Asp) and relevant metabolic enzymes in
      Arabidopsis thaliana. During germination and growth of the plant, a transient
      increase in D-Asp levels was observed, suggesting that D-Asp is synthesized in
      the plant. Administration of D-Asp suppressed growth, although the inhibitory
      mechanism responsible for this remains to be clarified. Exogenous D-Asp was
      efficiently incorporated and metabolized, and was converted to other D-amino
      acids (D-Glu and D-Ala). We then studied the related metabolic enzymes, and
      consequently cloned and characterized A. thaliana D-amino acid aminotransferase,
      which is presumably involved in the metabolism of D-Asp in the plant by
      catalyzing transamination between D-amino acids. This is the first report of cDNA
      cloning and functional characterization of a D-amino acid aminotransferase in
      eukaryotes. The results presented here provide important information for
      understanding the significance of D-amino acids in the metabolism of higher
      plants.

PMID- 18318837
TI  - A comparative analysis of the transcriptome and signal pathways in hepatic
      differentiation of human adipose mesenchymal stem cells.
AB  - The specific features of the plasticity of adult stem cells are largely unknown.
      Recently, we demonstrated the hepatic differentiation of human adipose tissue
      derived mesenchymal stem cells (AT-MSCs). To identify the genes responsible for
      hepatic differentiation, we examined the gene expression profiles of AT-MSC
      derived hepatocytes (AT-MSC-Hepa) using several microarray methods. The resulting
      sets of differentially expressed genes (1639 clones) were comprehensively
      analyzed to identify the pathways expressed in AT-MSC-Hepa. Clustering analysis
      revealed a striking similarity of gene clusters between AT-MSC-Hepa and the whole
      liver, indicating that AT-MSC-Hepa were similar to liver with regard to gene
      expression. Further analysis showed that enriched categories of genes and
      signaling pathways such as complementary activation and the blood clotting
      cascade in the AT-MSC-Hepa were relevant to liver-specific functions. Notably,
      decreases in Twist and Snail expression indicated that mesenchymal-to-epithelial
      transition occurred in the differentiation of AT-MSCs into hepatocytes. Our data
      show a similarity between AT-MSC-Hepa and the liver, suggesting that AT-MSCs are
      modulated by their environmental conditions, and that AT-MSC-Hepa may be useful
      in basic studies of liver function as well as in the development of stem cell
      based therapy.

PMID- 18318838
TI  - Primary structure and function of a cytotoxic outer-membrane protein (ComP) of
      Plesiomonas shigelloides.
AB  - We previously isolated and characterized a 40-kDa cytotoxic outer-membrane
      protein (ComP) produced by Plesiomonas shigelloides strain P-1 (P-1). Sequence
      analysis of the comP gene revealed a coding region of 1068 bp, with a predicted
      mature protein composed of 335 amino acids and a molecular mass of 38.597 kDa.
      Three-dimensional structural modeling of ComP suggests that it has a beta-barrel
      structure with 16 transmembrane strands, eight short periplasmic turns and eight
      external loops. blast search results and protein modeling suggest that ComP may
      be a novel porin protein of P. shigelloides. In order to understand the role of
      ComP during P. shigelloides infection, we constructed a deletion mutant strain
      (P. shigelloides DeltacomP; P-1201), and compared the pathogenicity of P-1201 vs.
      the wild-type strain P-1 in Caco-2 cells. Unlike P-1, the deletion strain P-1201
      was not cytotoxic to Caco-2 cells and did not lead to apoptosis. These data
      indicate that ComP may be the predominant virulence factor that triggers cell
      death in the host cells following infection.

PMID- 18318839
TI  - Genomic organization of a polygalacturonase gene from a hyperpectinolytic mutant
      strain of Penicillium occitanis.
AB  - The pga1 gene encoding an endopolygalacturonase was isolated from a
      hyperpectinolytic mutant strain of Penicillium occitanis. It consists of an ORF
      of 1.155 kbp encoding a putative protein of 346 amino acids with a predicted
      molecular mass of 39 kDa, belonging to the family 28 of glycosyl hydrolases. The
      deduced amino acid sequence comprises a putative 38 N terminal amino acids of the
      prepropeptide. The nature and position of amino acids comprising the active site
      as well as the overall three-dimensional structure were well conserved between
      the P. occitanis pga1 and all polygalacturonases. The coding region of the pga1
      gene is interrupted by three short introns of 57, 53 and 65 bp in length. In
      addition to the determination of the transcription start site, the promoter
      sequence from the pga1 gene was analysed. It showed the conservation of known
      response elements for CreA and Hap2-3-4 factors. Southern blot analysis at high
      stringency shows that the isolated polygalacturonase gene exists as a single copy
      in the fungus genome. Northern blot analysis confirmed the constitutive
      hyperpectinolytic nature of the hyperpectinolytic CT1 mutation as high levels of
      pga1 mRNA were observed either on pectin or on glucose-grown cells.

PMID- 18318840
TI  - MJ0400 from Methanocaldococcus jannaschii exhibits fructose-1,6-bisphosphate
      aldolase activity.
AB  - The central carbon metabolism is well investigated in bacteria, but this is not
      the case for archaea. MJ0400-His(6) from Methanocaldococcus jannaschii catalyzes
      the cleavage of fructose-1,6-bisphosphate (FBP) to glyceraldehyde-3-phosphate and
      dihydroxyacetone phosphate with a V(max) of 33 mU mg(-1) and a K(m) of 430 microM
      at 50 degrees C. MJ0400-His(6) is inhibited competitively by erythrose-4
      phosphate with a K(i) of 380 microM and displays heat stability with a half-life
      of c. 1 h at 100 degrees C. Hence, MJ0400 is the second gene encoding for an FBP
      aldolase in M. jannaschii. Previously, MJ0400 was shown to act as an 2-amino-3,7
      dideoxy-D-threo-hept-6-ulosonic acid synthase. This indicates that MJ0400 is
      involved in both the carbon metabolism and the shikimate pathway in M.
      jannaschii.

PMID- 18318841
TI  - Comparative analysis of the complete mitochondrial genomes of Aspergillus niger
      mtDNA type 1a and Aspergillus tubingensis mtDNA type 2b.
AB  - To understand the differences in the organization of mitochondrial genomes of the
      very closely related Aspergillus niger and Aspergillus tubingensis species, we
      determined the complete genome sequence of the 1a mtDNA type of A. niger and 2b
      mtDNA type of A. tubingensis and now we provide a comparative analysis of the two
      mtDNAs. We found that (1) the organization (gene content and order) of the two
      genomes is almost identical and (2) the size difference between them is
      principally attributed to the different intron content of their cox1, atp9 and
      ndh4L genes.

PMID- 18318842
TI  - Inhibition of swarming motility of Pseudomonas aeruginosa by branched-chain fatty
      acids.
AB  - Pseudomonas aeruginosa is capable of moving by swimming, swarming, and twitching
      motilities. In this study, we investigated the effects of fatty acids on
      Pseudomonas aeruginosa PAO1 motilities. A branched-chain fatty acid (BCFA)--12
      methyltetradecanoic acid (anteiso-C15:0)--has slightly repressed flagella-driven
      swimming motility and completely inhibited a more complex type of surface
      motility, i.e. swarming, at a concentration of 10 microg mL(-1). In contrast,
      anteiso-C15:0 exhibited no effect on pili-mediated twitching motility. Other
      BCFAs and unsaturated fatty acids tested in this study showed similar inhibitory
      effects on swarming motility, although the level of inhibition differed between
      these fatty acids. These fatty acids caused no significant growth inhibition in
      liquid cultures. Straight-chain saturated fatty acids such as palmitic acid were
      less effective in swarming inhibition. The wetness of the PAO1 colony was
      significantly reduced by the addition of anteiso-C15:0; however, the production
      of rhamnolipids as a surface-active agent was not affected by the fatty acid. In
      addition to motility repression, anteiso-C15:0 caused 31% repression of biofilm
      formation by PAO1, suggesting that BCFA could affect the multiple cellular
      activities of Pseudomonas aeruginosa.

PMID- 18318843
TI  - Laterally transferred genomic islands in Xanthomonadales related to pathogenicity
      and primary metabolism.
AB  - Lateral gene transfer (LGT) is considered as one of the drivers in bacterial
      genome evolution, usually associated with increased fitness and/or changes in
      behavior, especially if one considers pathogenic vs. non-pathogenic bacterial
      groups. The genomes of two phytopathogens, Xanthomonas campestris pv. campestris
      and Xanthomonas axonopodis pv. citri, were previously inspected for genome
      islands originating from LGT events, and, in this work, potentially early and
      late LGT events were identified according to their altered nucleotide
      composition. The biological role of the islands was also assessed, and
      pathogenicity, virulence and secondary metabolism pathways were functions highly
      represented, especially in islands that were found to be recently transferred.
      However, old islands are composed of a high proportion of genes related to cell
      primary metabolic functions. These old islands, normally undetected by
      traditional atypical composition analysis, but confirmed as product of LGT by
      atypical phylogenetic reconstruction, reveal the role of LGT events by replacing
      core metabolic genes normally inherited by vertical processes.

PMID- 18318844
TI  - Rural and remote public health in Australia: an introduction to the special
      issue.

PMID- 18318845
TI  - Rural and remote public health in Australia: building on our strengths.

PMID- 18318846
TI  - Addressing the health disadvantage of rural populations: how does epidemiological
      evidence inform rural health policies and research?
AB  - We reviewed evidence of any apparently significant 'rural-urban' health status
      differentials in developed countries, to determine whether such differentials are
      generic or nation-specific, and to explore the nature and policy implications of
      determinants underpinning rural-urban health variations. A comprehensive
      literature review of rural-urban health status differentials within Australia,
      New Zealand, Canada, the USA, the UK, and a variety of other western European
      nations was undertaken to understand the differences in life expectancy and cause
      specific morbidity and mortality. While rural location plays a major role in
      determining the nature and level of access to and provision of health services,
      it does not always translate into health disadvantage. When controlling for major
      risk determinants, rurality per se does not necessarily lead to rural-urban
      disparities, but may exacerbate the effects of socio-economic disadvantage,
      ethnicity, poorer service availability, higher levels of personal risk and more
      hazardous environmental, occupational and transportation conditions. Programs to
      improve rural health will be most effective when based on policies which target
      all risk determinants collectively contributing to poor rural health outcomes.
      Focusing solely on 'area-based' explanations and responses to rural health
      problems may divert attention from more fundamental social and structural
      processes operating in the broader context to the detriment of rural health
      policy formulation and remedial effort.

PMID- 18318847
TI  - Implementing a chronic disease strategy in two remote Indigenous Australian
      settings: a multi-method pilot evaluation.
AB  - OBJECTIVE: To test an evaluation framework designed to evaluate implementation of
      the North Queensland Indigenous communities between August and December 2005.
      SETTING: Both communities are located in Cape York, North Queensland. Community A
      has an estimated population of around 600 people; Community B has an enumerated
      population of 750, although health centre records indicate a higher number.
      PARTICIPANTS: Process evaluation involved health centre staff in both
      communities; clinical audits used random samples from the adult population (each
      sample n = 30); ethnographic fieldwork was conducted with resident population.
      MAIN OUTCOME MEASURES: Health centre scores and qualitative findings using a
      System Assessment Tool; clinical audits--extent to which scheduled services
      recorded; selected primary health performance indicators; qualitative
      ethnographic findings. RESULTS: On almost all indicators, implementation of
      NQICDS had progressed further in Community A than in Community B; however, some
      common issues emerged, especially lack of linkages between health centres and
      other groups, and lack of support for client self-management. CONCLUSIONS: The
      evaluation framework is an effective and acceptable framework for monitoring
      implementation of the NQICDS at the primary health centre level.

PMID- 18318848
TI  - Lukumbat marawana: a changing pattern of drug use by youth in a remote Aboriginal
      community.
AB  - OBJECTIVE: To examine marijuana use by youth in a remote Aboriginal community in
      Northern Australia over a 5-year period. DESIGN: Participant observation,
      structured and unstructured interviews. SETTING: Remote Indigenous Australian
      community. PARTICIPANTS: Young Aboriginal people and adult community members.
      MAIN OUTCOME MEASURE: Emergent themes of the attitudes towards marijuana use
      among remote Indigenous residents are reported. RESULTS: Restrictions in the
      availability of alcohol and petrol have led to increased use of marijuana with
      serious social and community consequences. CONCLUSIONS: Efforts to control licit
      substances, such as alcohol, in remote communities need to be addressed in the
      context of understanding of the dynamics of alcohol and drug use in totality as
      well as interventions that address underlying structural and social inequalities.

PMID- 18318849
TI  - Mobilising a rural community to lose weight: impact evaluation of the
      WellingTonne Challenge.
AB  - OBJECTIVE: To evaluate the impact of the WellingTonne Challenge. DESIGN: Before
      after study. SETTING: The National Action Agenda for the prevention and control
      of obesity in Australia identified community action and development as a key
      theme. The WellingTonne Challenge was a whole-of-community project designed to
      support a small rural community to lose weight and reduce their risk of chronic
      disease. PARTICIPANTS: Adult residents of the Wellington Local Government Area
      who were overweight or obese. RESULTS: The project successfully engaged the
      community with around 10% of the target group formally participating in the
      Challenge. Participants achieved a weight reduction of around 3 kg each, as well
      as positive changes in diet and physical activity. A total of 59% of those who
      signed up for the Challenge achieved an accumulated loss of 687 kg at the end of
      the 12-week program--less than the community goal of 1000 kg. CONCLUSION: The
      WellingTonne Challenge is a promising intervention. Wider implementation of this
      approach in other small rural communities might make a significant contribution
      to the national effort. The opportunity should be taken to undertake a more
      rigorous evaluation to determine whether this approach benefits communities in
      the longer term.

PMID- 18318850
TI  - Rural obesity, healthy weight and perceptions of risk: struggles, strategies and
      motivation for change.
AB  - OBJECTIVE: To explore risk logics, embodiment (the interplay between the
      physical, social and subjective body) and issues related to adult obesity in
      remote New South Wales. DESIGN: Qualitative multiple-method design using
      semistructured interviews and visual aids (food and exercise palm cards) to
      explore the saliency of food and exercise options. A one-page demographic survey
      incorporated self-reported body mass index. PARTICIPANTS: A total of 19 rural
      adults (13 female; six male). SETTING: Community in remote New South Wales,
      Australia. RESULTS: Thematic analysis revealed 14 major weight-related themes.
      Respondents raised numerous explanations for their weight gain, reported
      struggles with weight loss, revealed a range of motivations for weight loss and a
      variety of approaches to risk, not all of which are aligned to dominant health
      discourse. The need for realistic interventions incorporating social meaning and
      pleasure seeking is revealed. CONCLUSION: Obesity interventions promoting 'easy'
      healthy choices also need to acknowledge embodiment and social status linked to
      consumption. Interventions that ignore the complexity surrounding consumption
      (e.g. the interplay of social taste, group distinction and embodiment) will have
      lower relevance and effectiveness.

PMID- 18318851
TI  - Physical activity behaviours of adults in the Greater Green Triangle region of
      rural Australia.
AB  - OBJECTIVE: To assess physical activity (PA) behaviours of adults in rural
      Australia. DESIGN AND SETTING: Three cross-sectional surveys in the Greater Green
      Triangle area covering the south-east of South Australia (Limestone Coast), and
      south-west (Corangamite Shire) and north-west (Wimmera) of Victoria during 2004
      2006. PARTICIPANTS: A total of 1546 persons, aged 25- 74 years, randomly selected
      from the electoral roll. MAIN OUTCOME MEASURES: Overall PA, leisure-time PA,
      occupational PA, active commuting and moderate-to-vigorous PA. RESULTS:
      Approximately 80% of participants, more women than men, engaged in 30 minutes or
      more of daily PA. Only 30% (95% CI 26.3, 33.0) of men and 21% (95% CI 18.3, 23.9)
      of women did moderate-to-vigorous PA for at least 20-30 minutes four or more
      times a week. In leisure time, most participants were moderately active; almost
      one-fifth were inactive and another fifth highly active. Two-thirds of men
      engaged in high-level occupational PA, compared with one-sixth of women. Only 30%
      of participants actively commuted to work. There was a tendency for a positive
      association between income level and leisure-time PA. CONCLUSIONS: One-fifth of
      adults in rural Australia were inactive. While there was a high prevalence of
      participants who engaged in daily PA, few did so at moderate-to-vigorous
      intensity to achieve health benefits. As occupational PA is difficult to change,
      improvements in levels of PA are more likely during leisure-time and for some
      people by engaging in commuting PA.

PMID- 18318852
TI  - An evaluation of a community pharmacy-based rural asthma management service.
AB  - OBJECTIVE: To compare the effect of a pharmacist-delivered rural asthma
      management service (RAMS) on health outcomes for people with asthma in a
      rural/regional area with 'standard care' delivered through community pharmacies.
      DESIGN: A parallel group controlled repeated measures study. SETTING: Community
      pharmacies in Central West New South Wales. INTERVENTION: Standardised protocols
      and resources based on national asthma management guidelines, delivered by
      specially trained community pharmacists. Patients visited the pharmacy at
      baseline and 1, 3 and 6 months after baseline in the intervention group and at
      baseline plus 6 months after baseline in the control group. PARTICIPANTS: The
      intervention pharmacists (n = 12) were trained to deliver the RAMS model, while
      control pharmacists (n = 8) provided standard asthma care to their recruited
      patients. Fifty-one and 39 patients were recruited by intervention and control
      pharmacists. MAIN OUTCOME MEASURE: Asthma severity score which was a composite
      score based on recency, frequency and severity of asthma symptoms, and asthma
      history. RESULTS: Data compared at the final visit between groups indicated that
      the RAMS patient group demonstrated a significant reduction in the asthma
      severity scores (7.9 +/- 2.6 versus 10.4 +/- 2.6, P < 0.001); a reduction in the
      risk of non-adherence to medication scores (1.6 +/- 0.7 versus 2.3 +/- 1.1, P <
      0.001); and an increase in the proportion of patients owning a written action
      plan (50% versus 23%, P = 0.04). CONCLUSIONS: These results indicated that the
      community pharmacy-based RAMS model can improve asthma outcomes for patients in
      rural settings, and similar models for asthma and other chronic diseases should
      be tested rigorously and adopted in rural primary care practice.

PMID- 18318853
TI  - Evaluation of iodine levels in the Riverina population.
AB  - OBJECTIVE: To assess the iodine status in a random group of adults in a rural
      region. DESIGN: A cross-sectional study; urinary iodine concentrations (UIC) were
      correlated with results of a questionnaire that collected demographic
      information. SETTING: Primary care. PARTICIPANTS: A total of 173 adults from the
      Riverina region provided a morning midstream urine sample and completed a
      questionnaire. There were no exclusion criteria. MAIN OUTCOME MEASURES: Iodine
      status was based upon mean UIC (MUIC) values and categorised according to World
      Health Organisation criterion. Subgroups were classified according to sex, age,
      town, salt usage, vitamin/supplement usage, pregnant or breast-feeding status and
      diet. RESULTS: The MUIC for the study population was 79 microg L(-1); 29% were
      iodine-replete, 52% had mild deficiency and 18.5% were moderately to severely
      deficient. Use of iodised salt produced a non-clinically significant increase in
      MUIC of 81 microg L(-1)compared with 71 microg L(-1)(P = 0.1907). Daily vitamin
      supplementation led to iodine sufficiency with a MUIC of 111 microg L(-1)(P =
      0.0011). Participants aged 50-59 years had a significantly lower MUIC than
      participants aged 18-39 years (67 versus 89 microg L(-1), respectively, P =
      0.0106). Further, the MUIC decreased with age from 18 to 59 years (P = 0.0208).
      CONCLUSIONS: A mild iodine deficiency was found in this sample of the Riverina
      population, consistent with other Australian studies. Salt iodisation might not
      be an effective strategy to correct iodine deficiencies within Australia.

PMID- 18318854
TI  - Feeling safe in one's neighbourhood: variation by location among older
      Australians.

PMID- 18318855
TI  - Health workforce crisis: how to achieve a work-life balance.

PMID- 18318856
TI  - NRF: Mental health support for rural practitioners.

PMID- 18318857
TI  - A hierarchical view of convergent evolution in microbial eukaryotes.
AB  - Distinguishing convergent evolution from other causes of similarity in organisms
      is necessary for reconstructing phylogenetic relationships, inferring patterns of
      character evolution, and investigating the forces of natural selection. In
      contrast to animals and land plants, the pervasiveness and adaptive significance
      of convergent evolution in microbes has yet to be systematically explored or
      articulated. Convergent evolution in microbial eukaryotes, for instance, often
      involves very distantly related lineages with relatively limited repertoires of
      morphological features. These large phylogenetic distances weaken the role of
      ancestral developmental programs on the subsequent evolution of morphological
      characters, making convergent evolution between very distantly related lineages
      fundamentally different from convergent evolution between closely related
      lineages. This suggests that examples of convergence at different levels in the
      phylogenetic hierarchy offer different clues about the causes and processes of
      macroevolutionary diversification. Accordingly (and despite opinions to the
      contrary), I recognize three broad and overlapping categories of phenotypic
      convergence-"parallel", "proximate" and "ultimate"-that represent either (1)
      subcellular analogues, (2) subcellular analogues to multicellular systems (and
      vice versa), or (3) multicellular analogues. Microbial eukaryotes living in
      planktonic environments, interstitial environments, and the intestinal
      environments of metazoan hosts provide compelling examples of ultimate
      convergence. After describing selected examples in microbial eukaryotes, I
      suggest some future directions needed to more fully understand the hierarchical
      structure of convergent evolution and the overall history of life.

PMID- 18318858
TI  - Adaptation of the fungal parasite Zygorhizidium planktonicum during 200
      generations of growth on homogeneous and heterogeneous populations of its host,
      the diatom Asterionella formosa.
AB  - We followed adaptation of the chytrid parasite Zygorhizidium planktonicum during
      200 generations of growth on its host, the freshwater diatom Asterionella
      formosa, in a serial passage experiment. Evolution of parasite fitness was
      assessed both on a homogenous and heterogeneous host population, consisting of
      respectively a single new and ten different new host strains. These 10 host
      strains were genetically different and also varied in their initial
      susceptibility to the parasite. Parasite fitness increased significantly and
      rapidly on the new, genetically homogenous host population, but remained
      unaltered during 200 generations of growth on the heterogeneous host population.
      Enhanced parasite fitness was the result of faster and more efficient
      transmission, resulting in higher values of R0 (number of secondary infections).
      Consequently, parasites that evolved within the uniclonal host population
      infected significantly more of these hosts than did their ancestors. We thus
      provide experimental evidence for the widely held view that host genetic
      diversity restricts evolution of parasites and moderates their harmful effects.
      Genetically uniform host populations are not only at increased risk from fungal
      epidemics because they all share the same susceptibility, but also because new
      parasite strains are able to adapt quickly to new host environments and to
      improve their fitness.

PMID- 18318859
TI  - Redescription of the tintinnid Stenosemella pacifica Kofoid and Campbell, 1929
      (Ciliophora, Spirotricha) based on live observation, protargol Impregnation, and
      Scanning Electron Microscopy.
AB  - The tintinnid ciliate Stenosemella pacifica Kofoid and Campbell, 1929 was
      occasionally recorded from the pelagial of temperate, subtropical, and tropical
      neritic waters. Since its cytological features were unknown, the species is
      redescribed from material collected in the pelagial of the Irish Sea, using live
      observation, protargol impregnation, and scanning electron microscopy.
      Furthermore, the species diagnosis is improved to include new characteristics,
      e.g. the somatic ciliary pattern comprising a ventral, dorsal, and posterior
      kinety as well as a right, left, and lateral ciliary field. The stomatogenesis of
      S. pacifica is typical for species with such a complex somatic ciliary pattern:
      the oral primordium develops hypoapokinetally posterior to the lateral ciliary
      field. The presence of windows in the lorica collar of Stenosemella ventricosa,
      the type of the genus, necessitates (i) an improved genus diagnosis, (ii) a
      synonymization of the genus LuminellaKofoid and Campbell, 1939, and (iii) a
      transfer of the Luminella species to the genus Stenosemella, including Luminella
      neocalifornica, which becomes Stenosemella neocalifornica nov. comb. Owing to the
      lack of a description, Stenosemella crateri is considered a nomen nudum.

PMID- 18318860
TI  - A comparison of the polycation receptors of Paramecium tetraurelia and
      Tetrahymena thermophila.
AB  - Chemorepellents are compounds that cause ciliated protozoans to reorient their
      swimming direction. A number of chemorepellents have been studied in the ciliated
      protozoans, Paramecium and Tetrahymena. Chemorepellents, such as polycations,
      cause the organism to exhibit "avoidance behavior," a swimming behavior
      characterized by jerky movements and other deviations from normal forward
      swimming, which result from ciliary reversal. One well-characterized
      chemorepellent pathway in Tetrahymena is that of the proposed polycation receptor
      that is activated by lysozyme and pituitary adenylate cyclase activating
      polypeptide (PACAP). In this study, we compare the response of Paramecium to the
      chemorepellents lysozyme, vasoactive intestinal peptide (VIP), and PACAP to the
      previously studied polycation response in Tetrahymena. Our results indicate that
      lysozyme, VIP, and PACAP are all chemorepellents in Paramecium, just as they are
      in Tetrahymena. However, the signaling pathways involved appear to be different.
      While previous pharmacological characterization indicates that G-proteins are
      involved in polycation signaling in Tetrahymena, we present evidence that similar
      reception in Paramecium involves activation of a tyrosine kinase pathway in order
      for lysozyme avoidance to occur. Polycation responses of both organisms are
      inhibited by neomycin sulfate. While PACAP is the most effective of the three
      chemorepellents in Tetrahymena, lysozyme is the most effective chemorepellent in
      Paramecium.

PMID- 18318861
TI  - Morphological variation and phylogenetic analysis of the dinoflagellate
      Gymnodinium aureolum from a tributary of Chesapeake Bay.
AB  - Cultures of four strains of the dinoflagellate Gymnodinium aureolum (Hulburt) G.
      Hansen were established from the Elizabeth River, a tidal tributary of the
      Chesapeake Bay, USA. Light microscopy, scanning electron microscopy, nuclear
      encoded large sub-unit rDNA sequencing, and culturing observations were conducted
      to further characterize this species. Observations of morphology included: a
      multiple structured apical groove; a peduncle located between the emerging points
      of the two flagella; pentagonal and hexagonal vesicles on the amphiesma;
      production and germination of resting cysts; variation in the location of the
      nucleus within the center of the cell; a longitudinal ventral concavity; and
      considerable variation in cell width/length and overall cell size. A fish
      bioassay using juvenile sheepshead minnows detected no ichthyotoxicity from any
      of the strains over a 48-h period. Molecular analysis confirmed the
      dinoflagellate was conspecific with G. aureolum strains from around the world,
      and formed a cluster along with several other Gymnodinium species. Morphological
      evidence suggests that further research is necessary to examine the relationship
      between G. aureolum and a possibly closely related species Gymnodinium
      maguelonnense.

PMID- 18318862
TI  - The search finds an end: colpodidiids belong to the Class Nassophorea
      (ciliophora).
AB  - At its discovery in 1982, the ciliate genus Colpodidium was assigned to the Class
      Colpodea. Redescriptions of the type species Colpodidium caudatum caused the
      establishment of a new family (Colpodidiidae). Based on ontogenetic data,
      eventually a new order-Colpodidiida-was established and hypothesized to belong to
      the Class Nassophorea. Despite a remarkable increase in the number of colpodidiid
      species, no sequence data were available to confirm or reject either class
      assignment or to assess the phylogenetic validity of the Colpodidiidae and the
      Colpodidiida. We here retrieved and phylogenetically analyzed the SSrDNA
      sequences of C. caudatum from a Namibian soil and an as-yet undescribed
      colpodidiid ciliate from the Chobe River floodplain, Botswana. Bayesian inference
      methods and evolutionary distance analyses confirmed the assignment of these taxa
      to the class Nassophorea.

PMID- 18318863
TI  - Toward improvements of oomycete transformation protocols.
AB  - Some of the most important plant pathogens worldwide are oomycetes, and billions
      of dollars are expended annually to suppress diseases they cause. More efficient
      disease suppression technologies will be derived from a better understanding of
      the basic biology of these organisms, but inefficient transformation currently
      limits basic molecular investigations. Of the various approaches, transformation
      of protoplasts using polyethylene glycol/calcium chloride remains most
      successful, but the frequency of stable transformation remains low and
      inconsistent. Here we report that modifications of a protocol, previously used
      for Arabidopsis mesophyll cells, successfully releases protoplasts from four
      different oomycetes (Phytophthora citricola, Phytophthora infestans, Phytophthora
      sojae, and Pythium aphanidermatum). The protoplasts of all oomycetes were able to
      take up DNA and regenerate, with protoplast release as well as regeneration being
      most efficient in P. aphanidermatum. In addition to a good protoplast production
      system, more effective transformation vectors may improve stable transformation
      rates. We constructed, and evaluated 17 novel candidate transformation vectors
      for their ability to drive transient expression of the beta-glucuronidase (GUS)
      reporter gene in P. infestans and P. aphanidermatum. Five of the newly
      constructed vectors were also evaluated in P. sojae and P. citricola, and
      exhibited a similar pattern of transcriptional activity as in P. infestans and P.
      aphanidermatum. One of the newly constructed vectors, pDBHAMT35G, containing a
      chimeric promoter, supported the highest GUS expression in P. infestans and P.
      citricola, and could potentially be useful for future studies.

PMID- 18318864
TI  - Differentially expressed genes during fruiting body development in the
      aggregative ciliate Sorogena stoianovitchae (Ciliophora: Colpodea).
AB  - Sorogena stoianovitchae is the only ciliate that undergoes fruiting body
      development. Previously, we demonstrated that the developmental process is
      divided into five distinct stages: aggregation, compact aggregation, secretion of
      a mucous matrix, stalk elongation, and completion of the fruiting body. When S.
      stoianovitchae is mildly starved, several hundreds of cells aggregate beneath the
      water surface, and the aggregate develops into an aerial fruiting body. Essential
      requirements for fruiting body development are high-cell density, a light-dark
      cycle, and a dark period of more than 8 consecutive hours. In addition, the
      initial aggregation begins during the night, and light stimulation at sunrise
      triggers subsequent development. To elucidate the genes involved in fruiting body
      development, we carried out a reverse transcription-polymerase chain reaction (RT
      PCR) in cells before and after such development. Thirty-six sequences with stage
      specific expression patterns were cloned and partially sequenced. BLASTX search
      revealed that sequences with high identity for extracellular proteins (mucin,
      proteophosphoglycan) or membrane proteins (surface protein, TM9SF) are likely
      candidates for aggregation material, mucous matrix, and stalk material. Other
      sequences showed similarities to proteins, such as the casein kinase related to
      exocytosis in Paramecium, suggesting that they are involved in exocytosis
      signaling pathways for fruiting body development.

PMID- 18318865
TI  - Description of Perkinsus beihaiensis n. sp., a new Perkinsus sp. parasite in
      oysters of Southern China.
AB  - Oysters were collected from coastal locations in China from 1999-2006 for
      parasite analyses by molecular, culture, and histological techniques. Polymerase
      chain reaction-based assays targeting the internal transcribed spacer (ITS)
      region of the ribosomal RNA gene complex were performed to detect the presence of
      Perkinsus species. Sequencing and phylogenetic analysis of amplified Perkinsus
      sp. DNAs indicated that a novel Perkinsus sp. infects Crassostrea hongkongensis,
      Crassostrea ariakensis, and other bivalve hosts from Fujian to Guangxi provinces
      in southern China. Prevalence of this Perkinsus sp. reaches as high as 60% in
      affected oyster populations. Analyses of nucleotide sequences of the rRNA ITS
      region and of large subunit rRNA and actin genes, consistently confirmed the
      genus affiliation of this Perkinsus sp., but distinguished it from currently
      accepted Perkinsus species. Parasite cell types, such as signet ring trophozoites
      of 2-8 microm diameter, were observed by histology, and application of both genus
      Perkinsus and Perkinsus species-specific in situ hybridization probes
      consistently labelled the same Perkinsus sp. cells in histological sections from
      infected oyster tissues. Combined phylogenetic and histological results support
      the identity of a new parasite species, Perkinsus beihaiensis n. sp.

PMID- 18318866
TI  - Distinct localization patterns of two putative mitochondrial proteins in the
      microsporidian Encephalitozoon cuniculi.
AB  - Microsporidia were once considered amitochondriate, but have now been found to
      retain relict mitochondria called mitosomes. These organelles have been
      identified by immunolocalization in Trachipleistophora hominis, whereas most data
      on function have been inferred from the presence of mitochondrial protein
      encoding sequences in the genome of Encephalitozoon cuniculi. Here we describe
      the localization of two such enzymes in E. cuniculi cells. Immunofluorescent
      localization of ferredoxin involved in mitochondrial iron-sulfur cluster assembly
      reveals a punctate distribution as expected for mitochondria. In contrast,
      localization of mitochondrial glycerol-3-phosphate dehydrogenase suggests a
      cytoplasmic distribution in E. cuniculi and possible relocalization of this
      typically mitochondrial protein.

PMID- 18318867
TI  - Abortion in the United States: incidence and access to services, 2005.
AB  - CONTEXT: Accurate information about abortion incidence and services is necessary
      to monitor levels of unwanted pregnancy and women's ability to access abortion
      services. METHODS: All known abortion providers in the United States were
      contacted for information about abortion services in 2004 and 2005. This
      information, along with data from the U.S. Census Bureau, was used to examine
      national and state trends in numbers of abortions and abortion rates, proportions
      of counties and metropolitan areas without an abortion provider, and
      accessibility of abortion services. RESULTS: An estimated 1.2 million abortions
      were performed in the United States in 2005, 8% fewer than in 2000. The abortion
      rate in 2005 was 19.4 per 1,000 women aged 15-44; this rate represents a 9%
      decline from 2000. There were 1,787 abortion providers in 2005, only 2% fewer
      than in 2000. Some 87% of U.S. counties, containing 35% of women aged 15-44, did
      not have an abortion provider in 2005. Early medication abortion, offered by an
      estimated 57% of known providers, accounted for 13% of abortions (and for 22% of
      abortions before nine weeks' gestation). The average amount paid for an abortion
      at 10 weeks was $413-after adjustment for inflation, $11 less than in 2001.
      CONCLUSION: The numbers of abortions and the abortion rate continued their long
      term decline through 2005. Reasons for this trend are unknown but may include
      improved access to and use of contraceptives or decreased access to abortion
      services.

PMID- 18318868
TI  - Older sexual partners during adolescence: links to reproductive health outcomes
      in young adulthood.
AB  - CONTEXT: Sex at a young age with an older partner has been linked to poor
      reproductive health outcomes during adolescence, but minimal research has
      examined the influence of teenagers' having an older sexual partner on
      reproductive health outcomes during the transition to young adulthood. METHODS:
      Logistic regression and contrast analyses of three waves of data from the
      National Longitudinal Study of Adolescent Health were used to examine whether
      individuals who had had sex before age 16 with a partner at least three years
      their senior were at increased risk of becoming teenage or unmarried parents or
      of contracting an STD by young adulthood. RESULTS: Ten percent of females and 2%
      of males had had early sex with an older partner. These females were more likely
      to acquire an STD as young adults than were those whose riskiest relationship was
      before age 16 with a similar-aged partner (odds ratio, 2.1) or at age 16 or later
      with a similar-aged or older partner (2.4 and 2.6, respectively). For males,
      having sex before 16, regardless of partner age, was associated with an elevated
      STD risk (odds ratio, 1.9), although controlling for relationship history
      characteristics attenuated the association. CONCLUSIONS: Adolescents,
      particularly young adolescents, should be made aware of the potential risks
      associated with having older sexual partners. In particular, program providers
      should be alerted that females who engage in early sexual activity with older
      partners are at especially high risk of experiencing adverse reproductive health
      consequences.

PMID- 18318869
TI  - Sexual behavior of single adult American women.
AB  - CONTEXT: Public policies promoting abstinence until marriage attempt to influence
      the sexual behavior of the more than 18 million American women who are currently
      single. An analysis of these women's behavior is needed to inform policies that
      are responsive to their sexual and reproductive health needs. METHODS: Sexual
      behaviors, risk factors and reproductive health needs were examined among a
      nationally representative sample of 6,493 women aged 20-44 from the 2002 National
      Survey of Family Growth. Paired t tests were used to assess differences among
      single, married and cohabiting women by selected demographic, behavioral and risk
      measures. RESULTS: Thirty-six percent of women aged 20-44 are single, and nine in
      10 single women are sexually experienced. Seventy percent of the latter women are
      currently sexually active; on average, they had intercourse in seven of the last
      12 months. A higher proportion of single women (22%) than of cohabiting (9%) or
      married women (2%) have had two or more partners in the past year, and half of
      single women are at risk of unintended pregnancy. Furthermore, single women and
      cohabiting women are more likely to lack health insurance than are married women
      (21-25% vs. 12%). CONCLUSIONS: Because of the high level of sexual activity among
      single adult women, providers must address their reproductive health care needs
      and offer appropriate counseling and services. Government policies aimed at
      encouraging adult women to have sex only within marriage appear out of touch with
      the reality of the sexual behavior of single women.

PMID- 18318870
TI  - The impact of programs to increase contraceptive use among adult women: a review
      of experimental and quasi-experimental studies.
AB  - CONTEXT: Because rates of unintended pregnancy, abortion and unintended birth are
      very high among adult women in the United States, it is important to identify
      interventions that can increase contraceptive use in this population. METHODS:
      PubMed, PsycINFO and POPLINE were searched for experimental or quasi-experimental
      studies published between 1990 and 2005 that evaluated policies or programs
      designed to increase contraceptive use or reduce pregnancy among adult women in
      the United States. In addition, relevant journals were searched, experts were
      asked to provide further citations and several subsequently published articles
      were included. RESULTS: Only 11 studies that assessed programs, and none that
      assessed policies, were found. The evaluated interventions offered pregnancy and
      STD prevention counseling (one study); provided contraceptives in settings other
      than family planning clinics (two studies); had women initiate contraceptive use
      during the medical visit (two studies); provided advance supplies of emergency
      contraception (four studies); or implemented systems to remind injectable
      contraceptive users about their next injection (two studies). The interventions
      generally had positive, albeit short-term, effects on contraceptive use; none
      reduced pregnancy rates. Programs that gave women a contraceptive during the
      visit were the most effective at increasing method use. Advance provision of
      emergency contraception increased the likelihood of its use and did not affect
      regular contraceptive use. CONCLUSIONS: Very few studies have evaluated
      interventions to increase contraceptive use among adult women. A research plan
      that rigorously assesses the impact of different approaches to increasing
      contraceptive use among adult women should be an integral part of any long-term
      effort to prevent unintended pregnancy in the United States.

PMID- 18318871
TI  - Effects of a school-based, theory-driven HIV and pregnancy prevention curriculum.
AB  - CONTEXT: Although a number of interventions are effective at reducing risky
      adolescent sexual behavior, it may be possible to make them even more effective
      by addressing adolescents' approaches to risk-taking. METHODS: Schools were
      assigned to teach one of three curricula in a quasi-experimental intervention
      study: the school's standard pregnancy and HIV prevention curriculum; the
      Reducing the Risk curriculum; or a modified Reducing the Risk curriculum, adapted
      for high sensation seekers and impulsive decision makers. A sample of 1,944
      students from 17 schools was surveyed at three time points between 1995 and 1997.
      Mixed models regression and logistic regression were used to examine the
      difference in impact among curricula. RESULTS: Differences in the impact of the
      original and modified Reducing the Risk interventions were not significant for
      the total sample or for high sensation seekers and impulsive decision makers
      separately. Students from both intervention groups demonstrated short-term
      improvements in knowledge; students who received their schools' standard
      curriculum were significantly more likely than those assigned to either
      intervention to have initiated sexual intercourse by the third time point (odds
      ratio, 2.4). CONCLUSION: More work is necessary to understand the best ways to
      design classroom messages that will be effective in reducing the risk behaviors
      of high sensation seekers and impulsive decision makers.

PMID- 18318872
TI  - Abstracts of the 4th ELITA-ELTR (European Society for Organ Transplantation
      European Liver and Intestine Transplant Association) Winter Meeting. April 3-5,
      2008. Cortina d'Ampezzo, Italy.

PMID- 18318873
TI  - Optimising outcomes of hospital infections through appropriate empirical
      antimicrobial therapy. Introduction.

PMID- 18318874
TI  - Evolving problems with resistant pathogens.
AB  - Over the past decade, patterns of resistance to antimicrobial agents have changed
      dramatically, particularly because of the increasing prevalence of methicillin
      resistant Staphylococcus aureus (MRSA), as well as the increasing rate of
      antimicrobial resistance seen in several species of Gram-negative bacteria. The
      unique nature of the intensive care unit (ICU) environment makes it a focus for
      the emergence and spread of many antimicrobial-resistant pathogens. The patients
      in this setting are commonly exposed to broad-spectrum antimicrobial agents, and
      opportunities for the cross-transmission of resistant bacteria from patient to
      patient abound. Not surprisingly, resistance rates have increased for most
      pathogens associated with nosocomial infections among ICU patients, and rates are
      almost universally higher among ICU patients than among non-ICU patients. MRSA
      strains are now spreading in the community, possibly because of antibiotic
      pressure outside the hospital, but also because of transfer from hospital
      settings. Such strains are worrisome, particularly the strains carrying the gene
      for Panton-Valentine leukocidin (PVL), which has been associated with heightened
      virulence. Managing infections caused by today's pathogens requires avoidance of
      antimicrobial agent overuse and appropriate selection, dosing and duration of
      efficacious antimicrobial therapy.

PMID- 18318875
TI  - Appropriate vs. inappropriate antimicrobial therapy.
AB  - Inappropriate antimicrobial treatment (defined as use of antimicrobial agent to
      which a pathogen is resistant) or a delay in starting appropriate treatment are
      both associated with increased morbidity and mortality. Studies of ventilator
      associated pneumonia, intra-abdominal infections or bacteraemia document higher
      mortality in patients who received inappropriate therapy. In addition, the
      outcome in patients switched from inappropriate to appropriate therapy is better
      than for patients who remained on inappropriate therapy, but the benefit is not
      as great as for those who were started on appropriate therapy initially. While
      inappropriate therapy undoubtedly has an important influence on outcomes, it
      needs to be considered in the context of other patient risk-factors, such as co
      morbid conditions, severity score measures, and functional status. When assessing
      the impact of inappropriate therapy on outcomes such as length of hospital stay,
      it is important to be as precise as possible about the time of onset of
      infection. Failure to do so may lead to inaccurate estimation of the effect of
      inappropriate therapy. While the likelihood that resistant pathogens can increase
      costs throughout the healthcare system is generally recognised, an under
      appreciated aspect of resistance is its consequences for patients and their
      carers. Initiatives are underway to gauge the impact of resistance and strategies
      to combat its spread.

PMID- 18318876
TI  - Strategies for managing today's infections.
AB  - Bacterial infections are becoming more difficult to treat. At the present time c.
      70% of nosocomial infections are resistant to at least one antimicrobial drug
      that previously was effective for the causative pathogen. Pathogens that are
      notorious for their virulence and ability to develop resistance include
      Staphylococcus aureus, Enterococcus spp., members of the Enterobacteriaceae,
      Pseudomonas aeruginosa, and Acinetobacter species. Notable resistance patterns
      that have emerged include methicillin resistance in S. aureus, which started in
      the healthcare setting but has now moved into the community. Vancomycin
      resistance in enterococci is frequently seen, and vancomycin resistance in
      methicillin-resistant S. aureus is a public health threat. Resistance patterns
      seen in pseudomonal and Acinetobacter infections are rapidly shifting. The
      situation has become sufficiently serious for clinical opinion leaders to call
      upon governments for assistance in addressing the problem. In this worsening
      environment, in which patients are at progressively greater risk of untreatable
      infections, clear recommendations for prescribers are urgently needed. Severity
      of infection and underlying conditions are key issues, as patients with the most
      serious diseases are those in most urgent need, and improvements in our ability
      to predict likely infecting pathogens when empirical therapy is necessary are
      needed. Risk-factors and local resistance patterns must be accounted for, and
      initial empirical therapy should be adequately broad spectrum and adequately
      dosed. Agents must be highly active, able to penetrate adequately to the site of
      infection, safe, and well-tolerated.

PMID- 18318877
TI  - New and emerging treatment of Staphylococcus aureus infections in the hospital
      setting.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA), both hospital-acquired and
      community-acquired, is a dangerous pathogen that is involved in an increasing
      number of serious infections with high risk for morbidity and mortality.
      Community-acquired MRSA strains have epidemic potential and can be particularly
      virulent. Vancomycin has been the standard hospital treatment for the past 40
      years, but vancomycin-resistant isolates of S. aureus have emerged in the USA,
      and vancomycin-intermediate isolates are increasingly being reported worldwide.
      New antimicrobial agents with activity against multidrug-resistant S. aureus and
      other resistant pathogens are urgently needed. Despite great strides, further
      advances in our understanding of the molecular and biochemical mechanisms
      responsible for antimicrobial resistance are still required. Several agents have
      been recently approved for the treatment of serious Gram-positive infections,
      including linezolid, daptomycin, and tigecycline. The novel investigational
      cephalosporin, ceftobiprole, is one of the first penicillinase-resistant agents
      to target penicillin-binding protein 2a (or PBP2a), an acquired PBP with low beta
      lactam-affinity that confers intrinsic beta-lactam resistance to S. aureus and
      other staphylococci. This mechanism of PBP binding, including inhibition of
      PBP2a, confers broad-spectrum activity against clinically important Gram-negative
      and Gram-positive pathogens, including MRSA. Phase III clinical trials comparing
      ceftobiprole with vancomycin alone and in combination with ceftazidime for the
      treatment of complicated skin and skin structure infections showed ceftobiprole
      to have efficacy similar to the efficacy of these comparators as evidenced by non
      inferior clinical cure and microbiological eradication rates.

PMID- 18318878
TI  - Treatment of psychocutaneous diseases.

PMID- 18318879
TI  - Delusions of parasitosis.
AB  - Delusions of parasitosis is a rare psychiatric disorder in which the patient has
      a fixed, false belief that he or she is infested by parasites. Even though it is
      a psychiatric disorder, these patients usually present to a dermatologist because
      they are convinced that they have a dermatologic problem. Patients with delusions
      of parasitosis generally reject psychiatric referral. The traditional treatment
      of choice for delusions of parasitosis is the antipsychotic medication pimozide
      (Orap, Gate Pharmaceuticals, Philadelphia, PA). The use of pimozide has been
      limited by its adverse effects, most notably extrapyramidal adverse effects.
      There is now an emerging role for atypical antipsychotics with a safer adverse
      effect profile in the treatment of delusions of parasitosis. However, the most
      challenging aspect of managing these patients may be the challenge of
      establishing rapport in the face of unshakable delusional ideation.

PMID- 18318880
TI  - Morgellons disease?
AB  - Morgellons disease, a pattern of dermatologic symptoms very similar, if not
      identical, to those of delusions of parasitosis, was first described many
      centuries ago, but has recently been given much attention on the internet and in
      the mass media. The present authors present a history of Morgellons disease, in
      addition to which they discuss the potential benefit of using this diagnostic
      term as a means of building trust and rapport with patients to maximize treatment
      benefit. The present authors also suggest "meeting the patient halfway" and
      creating a therapeutic alliance when providing dermatologic treatment by taking
      their cutaneous symptoms seriously enough to provide both topical ointments as
      well as antipsychotic medications, which can be therapeutic in these patients.

PMID- 18318881
TI  - Trichotillomania.
AB  - Patients with trichotillomania often first present to dermatologists, as patients
      may be unaware of or deny hair pulling and seek an etiology for their hair loss.
      It therefore becomes the job of the dermatologist to correctly diagnose
      trichotillomania as well as offer treatment options. There appear to be three
      groups characterized by age of onset: preschool-age children, preadolescents to
      young adults, and adults. Young children often have a self-limited course of hair
      pulling. Adults frequently have psychiatric conditions associated with their
      trichotillomania. Preadolescents to young adults may benefit the most from active
      intervention, such as increasing awareness of hair pulling behaviors and behavior
      modification training. The approach of a patient by age of onset is helpful in
      guiding a dermatologist towards effective treatment options.

PMID- 18318882
TI  - Psychoneuroimmunology.
AB  - Psychoneuroimmunology (PNI) is a discipline that has evolved in the last 40 years
      to study the relationship between immunity, the endocrine system, and the central
      and peripheral nervous systems. In this manner, neurotransmitters, hormones, and
      neuropeptides have been found to regulate immune cells, and these in turn are
      capable of communicating with nervous tissue through the secretion of a wide
      variety of cytokines. Of critical importance is the effect of products of the CNS
      and nerves on the maintenance of the delicate balance between cell-mediated (Th1)
      and humoral (Th2) immune responses. A good example of how this concept operates
      in vivo becomes evident when analyzing the effects of stressors. Chronic stress
      affects significantly the function of the immune system as well as modifies the
      evolution of a variety of skin diseases, as psychosocial interventions have
      proved to be effective in their therapy.

PMID- 18318883
TI  - Neuropathic and psychogenic itch.
AB  - Neuropathic and psychogenic itch are two entities that have not been well
      studied. Neuropathic itch is related to pathology located at any point along the
      afferent pathway of the nervous system. It could be related to damage to the
      peripheral nervous system, such as in postherpetic neuropathy, brachioradial
      pruritus, notalgia paresthetica, and in central nervous system damage as a result
      of spinal cord tumors and demyelinization diseases such as multiple sclerosis. It
      has many clinical features similar to neuropathic pain. Patients complain of
      itch, which coincides with burning sensation, aching, and stinging. Psychogenic
      itch is related to psychologic abnormalities e.g., itch in obsessive compulsive
      disorders, depression, and delusions of parasitosis. Although no controlled
      studies have been conducted for treatment of neuropathic and psychogenic itch,
      medications that are part of the treatment armentarium for neuropathic pain,
      depression, and anxiety seem to be effective.

PMID- 18318884
TI  - Prurigo nodularis and lichen simplex chronicus.
AB  - Emotional tensions in predisposed subjects may play a key role in inducing a
      pruritic sensation, leading to a scratching that, becoming a self-perpetuating
      pathomechanism, may represent the main feature of two distinct cutaneous clinical
      entities: prurigo nodularis and lichen simplex chronicus. Psychogenic factors
      play a relevant role in both conditions, and they are often associated with
      depression and dissociative experiences. Hence, the importance of the evaluation
      of these patients from the point of view of psychodermatology, which may analyze
      the relationship between skin disease and psychological factors. Patients with
      real or perceived imperfections in particular areas of the body (face, scalp,
      hands, and genital area) are more prone to psychologic distress, whereas
      cutaneous diseases may lead to experience a heightened level of distress. As
      psychosomatic factors have been estimated to be present in at least one-third of
      dermatologic patients, effective management of skin conditions involves
      consideration of the associated emotional factors.

PMID- 18318885
TI  - Understanding the psychology of the cosmetic patients.
AB  - Patients seeking cosmetic surgery commonly present with psychiatric disorders
      including body dysmorphic disorder, narcissistic personality disorder, and
      histrionic personality disorder. A basic understanding of the characteristic
      features of these conditions and the importance of specialized screening
      questionnaires and preoperative interview questions are valuable to dermatologic
      surgeons as the information extracted can help provide clinicians with the most
      appropriate management including referral for psychiatric intervention.

PMID- 18318886
TI  - The psychosocial and occupational impact of chronic skin disease.
AB  - Chronic skin diseases, particularly psoriasis and atopic dermatitis, have a
      negative impact on patients' quality of life. Patients often experience
      significant psychological and social distress such as increased levels of
      depression and fear of stigma. Skin diseases can also impact patients'
      occupational lives by causing them to miss work or be less productive. Quality of
      life instruments provide important information for healthcare professionals, the
      general public, and those involved in distribution of healthcare resources, which
      helps prevent chronic skin disease from being overlooked amidst other medical
      conditions.

PMID- 18318887
TI  - Nonpharmacologic management of common skin and psychocutaneous disorders.
AB  - Data supporting the effectiveness of nonpharmacologic psychocutaneous techniques
      continues to accumulate. These interventions are used for the treatment of common
      and psychocutaneous skin conditions. They are most commonly used as adjuncts to
      traditional therapies. This article will review the data on the effectiveness of
      hypnosis, biofeedback, psychotherapy, meditation, support groups, guided imagery
      and progressive muscle relaxation, and psychotherapy.

PMID- 18318888
TI  - Psychopharmacology in dermatology.
AB  - Many patients with skin disorders have psychologic issues associated with their
      chief complaints. Dermatologists who wish to help their patients with
      psychodermatologic conditions can greatly enhance their therapeutic armamentarium
      by becoming familiar with the use of a few selected psychotropic agents. This
      paper will review the current status and future directions of psychopharmacology
      for the major types of psychopathologies encountered in a dermatology practice
      (depression, obsessive-compulsive disorder, anxiety, and delusional disorder)
      with the intent of guiding dermatologists in the choice of a psychotropic agent
      for patients with psychologic component to their skin disorder.

PMID- 18318890
TI  - One hub-one process: a tool based view on regulatory network topology.
AB  - BACKGROUND: The relationship between the regulatory design and the functionality
      of molecular networks is a key issue in biology. Modules and motifs have been
      associated to various cellular processes, thereby providing anecdotal evidence
      for performance based localization on molecular networks. RESULTS: To quantify
      structure-function relationship we investigate similarities of proteins which are
      close in the regulatory network of the yeast Saccharomyces Cerevisiae. We find
      that the topology of the regulatory network only show weak remnants of its
      history of network reorganizations, but strong features of co-regulated proteins
      associated to similar tasks. These functional correlations decreases strongly
      when one consider proteins separated by more than two steps in the regulatory
      network. The network topology primarily reflects the processes that is
      orchestrated by each individual hub, whereas there is nearly no remnants of the
      history of protein duplications. CONCLUSION: Our results suggests that local
      topological features of regulatory networks, including broad degree
      distributions, emerge as an implicit result of matching a number of needed
      processes to a finite toolbox of proteins.

PMID- 18318891
TI  - Prostaglandin E2 metabolism in rat brain: Role of the blood-brain interfaces.
AB  - BACKGROUND: Prostaglandin E2 (PGE2) is involved in the regulation of synaptic
      activity and plasticity, and in brain maturation. It is also an important
      mediator of the central response to inflammatory challenges. The aim of this
      study was to evaluate the ability of the tissues forming the blood-brain
      interfaces to act as signal termination sites for PGE2 by metabolic inactivation.
      METHODS: The specific activity of 15-hydroxyprostaglandin dehydrogenase was
      measured in homogenates of microvessels, choroid plexuses and cerebral cortex
      isolated from postnatal and adult rat brain, and compared to the activity
      measured in peripheral organs which are established signal termination sites for
      prostaglandins. PGE2 metabolites produced ex vivo by choroid plexuses were
      identified and quantified by HPLC coupled to radiochemical detection. RESULTS:
      The data confirmed the absence of metabolic activity in brain parenchyma, and
      showed that no detectable activity was associated with brain microvessels forming
      the blood-brain barrier. By contrast, 15-hydroxyprostaglandin dehydrogenase
      activity was measured in both fourth and lateral ventricle choroid plexuses from
      2-day-old rats, albeit at a lower level than in lung or kidney. The activity was
      barely detectable in adult choroidal tissue. Metabolic profiles indicated that
      isolated choroid plexus has the ability to metabolize PGE2, mainly into 13,14
      dihydro-15-keto-PGE2. In short-term incubations, this metabolite distributed in
      the tissue rather than in the external medium, suggesting its release in the
      choroidal stroma. CONCLUSION: The rat choroidal tissue has a significant ability
      to metabolize PGE2 during early postnatal life. This metabolic activity may
      participate in signal termination of centrally released PGE2 in the brain, or
      function as an enzymatic barrier acting to maintain PGE2 homeostasis in CSF
      during the critical early postnatal period of brain development.

PMID- 18318892
TI  - A global view of drug-therapy interactions.
AB  - BACKGROUND: Network science is already making an impact on the study of complex
      systems and offers a promising variety of tools to understand their formation and
      evolution in many disparate fields from technological networks to biological
      systems. Even though new high-throughput technologies have rapidly been
      generating large amounts of genomic data, drug design has not followed the same
      development, and it is still complicated and expensive to develop new single
      target drugs. Nevertheless, recent approaches suggest that multi-target drug
      design combined with a network-dependent approach and large-scale systems
      oriented strategies create a promising framework to combat complex multi-genetic
      disorders like cancer or diabetes. RESULTS: We here investigate the human network
      corresponding to the interactions between all US approved drugs and human
      therapies, defined by known relationships between drugs and their therapeutic
      applications. Our results show that the average paths in this drug-therapy
      network are shorter than three steps, indicating that distant therapies are
      separated by a surprisingly low number of chemical compounds. We also identify a
      sub-network composed by drugs with high centrality measures in the drug-therapy
      network, which represent the structural backbone of this system and act as hubs
      routing information between distant parts of the network. CONCLUSION: These
      findings provide for the first time a global map of the large-scale organization
      of all known drugs and associated therapies, bringing new insights on possible
      strategies for future drug development. Special attention should be given to
      drugs which combine the two properties of (a) having a high centrality value in
      the drug-therapy network and (b) acting on multiple molecular targets in the
      human system.

PMID- 18318893
TI  - Birth-death prior on phylogeny and speed dating.
AB  - BACKGROUND: In recent years there has been a trend of leaving the strict
      molecular clock in order to infer dating of speciations and other evolutionary
      events. Explicit modeling of substitution rates and divergence times makes
      formulation of informative prior distributions for branch lengths possible.
      Models with birth-death priors on tree branching and auto-correlated or iid
      substitution rates among lineages have been proposed, enabling simultaneous
      inference of substitution rates and divergence times. This problem has, however,
      mainly been analysed in the Markov chain Monte Carlo (MCMC) framework, an
      approach requiring computation times of hours or days when applied to large
      phylogenies. RESULTS: We demonstrate that a hill-climbing maximum a posteriori
      (MAP) adaptation of the MCMC scheme results in considerable gain in computational
      efficiency. We demonstrate also that a novel dynamic programming (DP) algorithm
      for branch length factorization, useful both in the hill-climbing and in the MCMC
      setting, further reduces computation time. For the problem of inferring rates and
      times parameters on a fixed tree, we perform simulations, comparisons between
      hill-climbing and MCMC on a plant rbcL gene dataset, and dating analysis on an
      animal mtDNA dataset, showing that our methodology enables efficient, highly
      accurate analysis of very large trees. Datasets requiring a computation time of
      several days with MCMC can with our MAP algorithm be accurately analysed in less
      than a minute. From the results of our example analyses, we conclude that our
      methodology generally avoids getting trapped early in local optima. For the cases
      where this nevertheless can be a problem, for instance when we in addition to the
      parameters also infer the tree topology, we show that the problem can be evaded
      by using a simulated-annealing like (SAL) method in which we favour tree swaps
      early in the inference while biasing our focus towards rate and time parameter
      changes later on. CONCLUSION: Our contribution leaves the field open for fast and
      accurate dating analysis of nucleotide sequence data. Modeling branch
      substitutions rates and divergence times separately allows us to include birth
      death priors on the times without the assumption of a molecular clock. The
      methodology is easily adapted to take data from fossil records into account and
      it can be used together with a broad range of rate and substitution models.

PMID- 18318894
TI  - Negotiating the transition from adolescence to motherhood: coping with prenatal
      and parenting stress in teenage mothers in Mulago hospital, Uganda.
AB  - BACKGROUND: Adolescence is a transitional stage from childhood to adulthood that
      is characterized by physical, physiological, psychosocial and behavioral changes
      that are influenced to a large extent by the age, culture and socialization of
      the individual. To explore what adolescent mothers perceive as their struggles
      during the period of transition from childhood to parenthood (through motherhood)
      and to describe strategies employed in coping with stress of pregnancy,
      motherhood and parenthood. METHODS: Longitudinal qualitative study involving
      twenty two in-depth interviews and six focus group discussions among pregnant
      adolescents who were followed from pregnant to delivery, from January 2004 to
      August 2005. Participant were selected by theoretical sampling and data was
      analyzed using grounded theory. RESULTS: Overall, young adolescents reported more
      anxiety, loss of self esteem (when they conceived), difficulty in accessing
      financial, moral and material support from parents or partners and stigmatization
      by health workers when they sought care from health facilities. Three strategies
      by which adolescent mothers cope with parenting and pregnancy stress that were
      described as utilizing opportunities (thriving), accommodating the challenges
      (bargaining and surviving), or failure (despairing), and varied in the extent to
      which they enabled adolescents to cope with the stress. CONCLUSION: Adolescents
      on the transition to motherhood have variable needs and aspirations and utilize
      different strategies to cope with the stress of pregnancy and parenthood.

PMID- 18318895
TI  - The incidence of low venous oxygen saturation on admission to the intensive care
      unit: a multi-center observational study in The Netherlands.
AB  - BACKGROUND: Low mixed or central venous saturation (S(c)vO2) can reveal global
      tissue hypoxia and therefore can predict poor prognosis in critically ill
      patients. Early goal directed therapy (EGDT), aiming at an ScvO2 >/= 70%, has
      been shown to be a valuable strategy in patients with sepsis or septic shock and
      is incorporated in the Surviving Sepsis Campaign guidelines. METHODS: In this
      prospective observational multi-center study, we determined central venous
      pressure (CVP), hematocrit, pH, lactate and ScvO2 or SvO2 in a heterogeneous
      group of critically ill patients early after admission to the intensive care
      units (ICUs) in three Dutch hospitals. RESULTS: Data of 340 acutely admitted
      critically ill patients were collected. The mean SvO2 value was > 65% and the
      mean ScvO2 value was > 70%. With mean CVP of 10.3 +/- 5.5 mmHg, lactate plasma
      levels of 3.6 +/- 3.6 and acute physiology, age and chronic health evaluation
      (APACHE II) scores of 21.5 +/- 8.3, the in-hospital mortality of the total
      heterogeneous population was 32.0%. A subgroup of septic patients (n = 125)
      showed a CVP of 9.8 +/- 5.4 mmHg, mean ScvO2 values of 74.0 +/- 10.2%, where only
      1% in this subgroup revealed a ScvO2 value < 50%, and lactate plasma levels of
      2.7 +/- 2.2 mmol/l with APACHE II scores 20.9 +/- 7.3. Hospital mortality of this
      subgroup was 26%. CONCLUSION: The incidence of low ScvO2 values for acutely
      admitted critically ill patients is low in Dutch ICUs. This is especially true
      for patients with sepsis/septic shock.

PMID- 18318896
TI  - Small-volume resuscitation with hyperoncotic albumin: a systematic review of
      randomized clinical trials.
AB  - BACKGROUND: Small-volume resuscitation can rapidly correct hypovolemia.
      Hyperoncotic albumin solutions, long in clinical use, are suitable for small
      volume resuscitation; however, their clinical benefits remain uncertain. METHODS:
      Randomized clinical trials comparing hyperoncotic albumin with a control regimen
      for volume expansion were sought by multiple methods, including computer searches
      of bibliographic databases, perusal of reference lists, and manual searching.
      Major findings were qualitatively summarized. In addition, a quantitative meta
      analysis was performed on available survival data. RESULTS: In all, 25 randomized
      clinical trials with a total of 1,485 patients were included. In surgery,
      hyperoncotic albumin preserved renal function and reduced intestinal edema
      compared with control fluids. In trauma and sepsis, cardiac index and oxygenation
      were higher after administration of hydroxyethyl starch than hyperoncotic
      albumin. Improved treatment response and renal function, shorter hospital stay
      and lower costs of care were reported in patients with liver disease receiving
      hyperoncotic albumin. Edema and morbidity were decreased in high-risk neonates
      after hyperoncotic albumin administration. Disability was reduced by therapy with
      hyperoncotic albumin in brain injury. There was no evidence of deleterious
      effects attributable to hyperoncotic albumin. Survival was unaffected by
      hyperoncotic albumin (pooled relative risk, 0.95; 95% confidence interval 0.78 to
      1.17). CONCLUSION: In some clinical indications, randomized trial evidence has
      suggested certain benefits of hyperoncotic albumin such as reductions in
      morbidity, renal impairment and edema. However, further clinical trials are
      needed, particularly in surgery, trauma and sepsis.

PMID- 18318897
TI  - Mortality in Dutch hospitals: trends in time, place and cause of death after
      admission for myocardial infarction and stroke. An observational study.
AB  - BACKGROUND: Patterns in time, place and cause of death can have an important
      impact on calculated hospital mortality rates. Objective is to quantify these
      patterns following myocardial infarction and stroke admissions in Dutch hospitals
      during the period 1996-2003, and to compare trends in the commonly used 30-day in
      hospital mortality rates with other types of mortality rates which use more
      extensive follow-up in time and place of death. METHODS: Discharge data for all
      Dutch admissions for index conditions (1996-2003) were linked to the death
      certification registry. Then, mortality rates within the first 30, 90 and 365
      days following admissions were analyzed for deaths occurring within and outside
      hospitals. RESULTS: Most deaths within a year after admission occurred within 30
      days (60-70%). No significant trends in this distribution of deaths over time
      were observed. Significant trends in the distribution over place of death were
      observed for both conditions. For myocardial infarction, the proportion of deaths
      after transfer to another hospital has doubled from 1996-2003. For stroke a
      significant rise of the proportion of deaths outside hospital was found. For MI
      the proportion of deaths attributed to a circulatory disease has significantly
      fallen overtime. Seven types of hospital mortality indicators, different in scope
      and observation period, all show a drop of hospital mortality for both MI and
      stroke over the period 1996-2003. For stroke the observed absolute reduction in
      death rate increases for the first year after admission, for MI the observed drop
      in 365-day overall mortality almost equals the observed drop in 30-day in
      hospital mortality over 1996-2003. CONCLUSION: Changes in the timing, place and
      causes of death following admissions for myocardial infarction and stroke have
      important implications for the definitions of in-hospital and post-admission
      mortality rates as measures of hospital performance. Although necessary for
      understanding mortality patterns over time, including within mortality rates
      deaths which occur outside hospitals and after longer periods following index
      admissions remain debatable and may not reflect actual hospital performance but
      probably mirrors transfer, efficiency, and other health care policies.

PMID- 18318898
TI  - Antidepressant drugs modulate growth factors in cultured cells.
AB  - BACKGROUND: Different classes of antidepressant drugs are used as a treatment for
      depression by activating the catecholinergic system. In addition, depression has
      been associated with decrease of growth factors, which causes insufficient axonal
      sprouting and reduced neuronal damage repair. In this study, antidepressant
      treatments are analyzed in a cell culture system, to study the modulation of
      growth factors. RESULTS: We quantified the transcription of several growth
      factors in three cell lines after application of antidepressant drugs by real
      time polymerase chain reaction. Antidepressant drugs counteracted against
      phorbolester-induced deregulation of growth factors in PMA-differentiated
      neuronal SY5Y cells. We also found indications in a pilot experiment that
      magnetic stimulation could possibly modify BDNF in the cell culture system.
      CONCLUSION: The antidepressant effects antidepressant drugs might be explained by
      selective modulation of growth factors, which subsequently affects neuronal
      plasticity.

PMID- 18318899
TI  - Antenatal counseling on breastfeeding -- is it adequate? A descriptive study from
      Pondicherry, India.
AB  - BACKGROUND: Antenatal counseling on breastfeeding and postnatal lactation support
      are likely to improve rates of exclusive breastfeeding. This descriptive study
      was undertaken to assess whether antenatal visits were utilized for promotion of
      exclusive breastfeeding in addition to the routine obstetric services. METHODS:
      This descriptive study was conducted at a tertiary hospital in Pondicherry,
      India. Every third primigravida mother admitted in the maternity ward from June
      to December 2005 was recruited. Among these 144 primigravida mothers, 108 who had
      a minimum of three antenatal visits ("booked") were included in the study. These
      108 mothers were administered a pre-tested semi-structured questionnaire on
      breastfeeding in the local language, Tamil, within 24 hours of giving birth.
      Appropriate flash cards with pictures were also used while administering the
      questionnaire. The awareness among mothers (both "counseled" and "not counseled")
      regarding health information pertaining to breastfeeding was assessed. RESULTS:
      Of the booked mothers, 21% (n = 23) had received some antenatal counseling about
      breastfeeding while 79% (n = 85) had not received any such counseling. Four
      percent had undergone breast examination during antenatal visits. Awareness
      related to breastfeeding among mothers in the "counseled" group was better than
      those in the "not counseled" group. Even in the "counseled" group, awareness
      among mothers with regard to correct breastfeeding technique and concept of
      continuing breastfeeding during illness in the baby was no different from those
      in the "not counseled" group. CONCLUSION: Existing antenatal counseling on
      breastfeeding is inadequate in the population studied and needs to be
      strengthened. Informing all pregnant women about the benefits and management of
      breastfeeding should be a priority during antenatal visits.

PMID- 18318900
TI  - Cardiovascular response to dobutamine stress predicts outcome in severe sepsis
      and septic shock.
AB  - INTRODUCTION: During septic shock, resistance to the haemodynamic effects of
      catecholamine vasopressors and inotropes is a well-recognised marker of mortality
      risk. However, the specific cardiovascular or metabolic response elements that
      are most closely associated with outcome have not been well defined. The
      objective of this study was to assess cardiovascular and metabolic responses to
      dobutamine as correlates of outcome in patients with severe sepsis or septic
      shock. METHODS: A prospective, non-randomised, non-blinded interventional study
      of graded dobutamine challenge (0, 5, 10, and 15 mug/kg/min) in adult patients
      who had undergone pulmonary artery catheterisation within 48 hours of onset of
      severe sepsis or septic shock (8 survivors/15 non-survivors) was performed.
      Radionuclide cineangiography during graded infusion was used to determine
      biventricular ejection fractions at each increment of dobutamine. RESULTS: In
      univariate analysis, a variety of cardiovascular or haemodynamic and oxygen
      transport or metabolic variables (at the point of maximum cardiac index response
      for a given subject) were associated with survival including: increased stroke
      volume index (p = 0.0003); right ventricular end-diastolic volume index (p =
      0.0047); left ventricular stroke work index (p = 0.0054); oxygen delivery index
      (p = 0.0084); cardiac index (p = 0.0093); systolic blood pressure/left
      ventricular end-systolic volume index ratio (p = 0.0188); left ventricular
      ejection fraction (p = 0.0160); venous oxygen content (p = 0.0208); mixed venous
      oxygen saturation (p = 0.0234); pulse pressure (p = 0.0403); decreased pulmonary
      artery diastolic pressure (p = 0.0133); systemic vascular resistance index (p =
      0.0154); extraction ratio (p = 0.0160); and pulmonary vascular resistance index
      (p = 0.0390). Increases of stroke volume index of greater than or less than 8.5
      mL/m2 were concordant with survival or death in 21 of 23 cases. Multivariate
      profile construction showed stroke volume index as the dominant discriminating
      variable for survival with the systolic blood pressure/left ventricular end
      systolic volume index ratio alone among all other variables significantly
      improving the model. CONCLUSION: Survivors maintain cardiac responsiveness to
      catecholamine stimulation during septic shock. Survival from severe sepsis or
      septic shock is associated with increased cardiac performance and contractility
      indices during dobutamine infusion. Further studies are required to determine
      whether these parameters are predictive of outcome in a larger severe
      sepsis/septic shock population.

PMID- 18318901
TI  - LEA (late embryogenesis abundant) proteins and their encoding genes in
      Arabidopsis thaliana.
AB  - BACKGROUND: LEA (late embryogenesis abundant) proteins have first been described
      about 25 years ago as accumulating late in plant seed development. They were
      later found in vegetative plant tissues following environmental stress and also
      in desiccation tolerant bacteria and invertebrates. Although they are widely
      assumed to play crucial roles in cellular dehydration tolerance, their
      physiological and biochemical functions are largely unknown. RESULTS: We present
      a genome-wide analysis of LEA proteins and their encoding genes in Arabidopsis
      thaliana. We identified 51 LEA protein encoding genes in the Arabidopsis genome
      that could be classified into nine distinct groups. Expression studies were
      performed on all genes at different developmental stages, in different plant
      organs and under different stress and hormone treatments using quantitative RT
      PCR. We found evidence of expression for all 51 genes. There was only little
      overlap between genes expressed in vegetative tissues and in seeds and expression
      levels were generally higher in seeds. Most genes encoding LEA proteins had
      abscisic acid response (ABRE) and/or low temperature response (LTRE) elements in
      their promoters and many genes containing the respective promoter elements were
      induced by abscisic acid, cold or drought. We also found that 33% of all
      Arabidopsis LEA protein encoding genes are arranged in tandem repeats and that
      43% are part of homeologous pairs. The majority of LEA proteins were predicted to
      be highly hydrophilic and natively unstructured, but some were predicted to be
      folded. CONCLUSION: The analyses indicate a wide range of sequence diversity,
      intracellular localizations, and expression patterns. The high fraction of
      retained duplicate genes and the inferred functional diversification indicate
      that they confer an evolutionary advantage for an organism under varying
      stressful environmental conditions. This comprehensive analysis will be an
      important starting point for future efforts to elucidate the functional role of
      these enigmatic proteins.

PMID- 18318902
TI  - Acute effects of caffeine and cigarette smoking on ventricular long-axis function
      in healthy subjects.
AB  - BACKGROUND: Few data exist regarding the direct effects of caffeine and smoking
      on cardiac function. We sought to explore the acute effects of caffeine
      assumption, cigarette smoking, or both on left ventricular (LV) and right
      ventricular (RV) function in a population of young normal subjects. METHODS:
      Forty-five healthy subjects aged 25 +/- 2 years underwent echocardiography.
      Fifteen of them were non-smokers and habitual coffee consumers (group 1), 15 were
      smokers and not habitual coffee consumers (group 2), and 15 were smokers and
      habitual coffee consumers (group 3). Peak systolic (Sa), early diastolic Ea, and
      late diastolic (Aa) velocity of mitral annulus were measured by pulsed Tissue
      Doppler, and left atrioventricular plane displacement was determined by M-mode.
      Tricuspid annular velocities and systolic excursion (TAPSE) were also determined.
      Measurements were performed at baseline and after oral assumption of caffeine 100
      mg in group 1, one cigarette smoking in group 2, and both in group 3. RESULTS: No
      changes in ventricular function were observed in group 1 after caffeine
      administration. In group 2, cigarette smoking yielded an acute increase in mitral
      Aa (+12.1%, p = 0.0026), tricuspid Sa (+9.8%, p = 0.012) and TAPSE (+7.9%, p =
      0.017), and a decrease in the mitral Ea/Aa ratio (-8.5%, p = 0.0084). Sequential
      caffeine assumption and cigarette smoking in group 3 was associated with an acute
      increase in mitral Aa (+13.0%, p = 0.015) and tricuspid Aa (+11.6%, p < 0.0001)
      and a reduction in mitral Ea/Aa ratio (-8.5%, p = 0.0084) tricuspid Ea (-6.6%, p
      = 0.048) and tricuspid Ea/Aa ratio (-9.6%, p = 0.0003). In a two-way ANOVA model
      controlling for hemodynamic confounding factors, changes in the overall
      population remained significant for mitral Aa and Ea/Aa ratio, and for tricuspid
      Aa and Ea/Aa ratio. CONCLUSION: In young healthy subjects, one cigarette smoking
      is associated to an acute impairment in LV diastolic function and a hyperdynamic
      RV systolic response. Caffeine assumption alone does not exert any acute effect
      on ventricular long-axis function, but potentiates the negative effect of
      cigarette smoking by abolishing RV supernormal response and leading to a
      simultaneous impairment in both LV and RV diastolic function.

PMID- 18318903
TI  - Sutureless prepuceplasty with wound healing by second intention: an alternative
      surgical approach in children's phimosis treatment.
AB  - BACKGROUND: A new technique for the treatment of children's phimosis is presented
      that minimizes the repairing time, the postoperative complications and maintains
      the physical foreskin appearance intact. METHODS: Eightyseven children with
      phimosis were treated with this new developed technique, between 2003 and 2005.
      Sutureless prepuceplasty creates a permanent surgical extension of the close
      prepuce. Stretching and retraction of phimotic foreskin reveals a tight prepuce
      ring that is cutting in its dorsal surface longitudinally. Rarely triple
      symmetric incisions in the preputial outlet are necessary. The foreskin is loose
      and moves absolutely free in bilateral courses. The wounds are healing by second
      intention. Antisepsis, steroids and Elicina cream, (which contains allantoin,
      collagen, elastin, glycolic acid and vitamins A, D, and E) should apply daily,
      for twenty to thirty days. RESULTS: The foreskin is moving in centripetal or
      efferent courses absolutely loosely, painlessly and bloodlessly. The mean time of
      follow-up was 27 months (one to four years). No complications were observed.
      CONCLUSION: Sutureless prepuceplasty may present an acceptable alternative in
      children's phimosis reconstruction.

PMID- 18318904
TI  - Pelvic radiography in ATLS algorithms: A diminishing role?
AB  - BACKGROUND: Pelvic x-ray is a routine part of the primary survey of
      polytraumatized patients according to Advanced Trauma Life Support (ATLS)
      guidelines. However, pelvic CT is the gold standard imaging technique in the
      diagnosis of pelvic fractures. This study was conducted to confirm the safety of
      a modified ATLS algorithm omitting pelvic x-ray in hemodynamically stable
      polytraumatized patients with clinically stable pelvis in favour of later pelvic
      examination by CT scan. METHODS: We conducted a retrospective analysis of all
      polytraumatized patients in our emergency room between 01.07.2004 and 31.01.2006.
      Inclusion criteria were blunt abdominal trauma, initial hemodynamic stability and
      a stable pelvis on clinical examination. We excluded patients requiring immediate
      intervention because of hemodynamic instability. RESULTS: We reviewed the records
      of n = 452 polytraumatized patients, of which n = 91 fulfilled inclusion criteria
      (56% male, mean age = 45 years). The mechanism of trauma included 43% road
      traffic accidents, 47% falls. In 68/91 (75%) patients, both a pelvic x-ray and a
      CT examination were performed; the remainder had only pelvic CT. In 6/68 (9%)
      patients, pelvic fracture was diagnosed by pelvic x-ray. None of these 6 patients
      was found having a false positive pelvic x-ray, i.e. there was no fracture on
      pelvic CT scan. In 3/68 (4%) cases a fracture was missed in the pelvic x-ray, but
      confirmed on CT (false negative on x-ray). None of the diagnosed fractures needed
      an immediate therapeutic intervention. 5 (56%) were classified type A fractures,
      and another 4 (44%) B 2.1 in computed tomography (AO classification). One A 2.1
      fracture was found in a clinically stable patient who only received CT scan
      (1/23). CONCLUSION: While pelvic x-ray is an integral part of ATLS assessment,
      this retrospective study suggests that in hemodynamically stable patients with
      clinically stable pevis, its sensitivity is only 67% and it may safely be omitted
      in favor of a pelvic CT examination if such is planned in adjunct assessment and
      available. The results support the safety and utility of our modified ATLS
      algorithm. A randomized controlled trial using the algorithm can safely be
      conducted to confirm the results.

PMID- 18318905
TI  - Career choices for ophthalmology made by newly qualified doctors in the United
      Kingdom, 1974-2005.
AB  - BACKGROUND: The paper aims to report trends in career choices for ophthalmology
      among UK medical graduates. METHODS: Postal questionnaire surveys were undertaken
      of qualifiers from all UK medical schools in nine qualification years since 1974.
      Data were analysed by univariate cross-tabulation. The significance of
      comparisons between groups of doctors were calculated by the use of chi-squared
      tests and adjusted residuals. RESULTS: Ophthalmology was the first choice of long
      term career for 2.3% of men and 1.5% of women one year after qualification; 2.0%
      of men and 1.4% of women three years after; and 1.8% of men and 1.2% of women at
      five years. Comparing early choices with eventual destinations, 64% who chose
      ophthalmology in year one, 84% in year three, and 92% in year five eventually
      practised in the specialty. The concordance between year one choice and eventual
      destination was higher for ophthalmology than for most other specialties.
      'Enthusiasm for and commitment to the specialty' was the most important single
      factor in influencing career choice. The prospect of good working hours and
      conditions was also an important influence: it influenced career choice a great
      deal for a higher percentage of those who chose ophthalmology (66% in the third
      year) than those who made other surgical choices (23%). CONCLUSION: Those
      choosing ophthalmology show a high level of commitment to it. Their commitment is
      strengthened by the prospect of attractive hours and working conditions. Many
      doctors who become ophthalmologists have already made their choice by the end of
      their first post-qualification year.

PMID- 18318906
TI  - The adaptive evolution of the mammalian mitochondrial genome.
AB  - BACKGROUND: The mitochondria produce up to 95% of a eukaryotic cell's energy
      through oxidative phosphorylation. The proteins involved in this vital process
      are under high functional constraints. However, metabolic requirements vary
      across species, potentially modifying selective pressures. We evaluate the
      adaptive evolution of 12 protein-coding mitochondrial genes in 41 placental
      mammalian species by assessing amino acid sequence variation and exploring the
      functional implications of observed variation in secondary and tertiary protein
      structures. RESULTS: Wide variation in the properties of amino acids were
      observed at functionally important regions of cytochrome b in species with more
      specialized metabolic requirements (such as adaptation to low energy diet or
      large body size, such as in elephant, dugong, sloth, and pangolin, and adaptation
      to unusual oxygen requirements, for example diving in cetaceans, flying in bats,
      and living at high altitudes in alpacas). Signatures of adaptive variation in the
      NADH dehydrogenase complex were restricted to the loop regions of the
      transmembrane units which likely function as protons pumps. Evidence of adaptive
      variation in the cytochrome c oxidase complex was observed mostly at the
      interface between the mitochondrial and nuclear-encoded subunits, perhaps
      evidence of co-evolution. The ATP8 subunit, which has an important role in the
      assembly of F0, exhibited the highest signal of adaptive variation. ATP6, which
      has an essential role in rotor performance, showed a high adaptive variation in
      predicted loop areas. CONCLUSION: Our study provides insight into the adaptive
      evolution of the mtDNA genome in mammals and its implications for the molecular
      mechanism of oxidative phosphorylation. We present a framework for future
      experimental characterization of the impact of specific mutations in the
      function, physiology, and interactions of the mtDNA encoded proteins involved in
      oxidative phosphorylation.

PMID- 18318907
TI  - Obesity and cardio-metabolic risk factors in urban adults of Benin: relationship
      with socio-economic status, urbanisation, and lifestyle patterns.
AB  - BACKGROUND: There is a dearth of information on diet-related chronic diseases in
      West Africa. This cross-sectional study assessed the rate of obesity and other
      cardiovascular disease (CVD) risk factors in a random sample of 200 urban adults
      in Benin and explored the associations between these factors and socio-economic
      status (SES), urbanisation as well as lifestyle patterns. METHODS: Anthropometric
      parameters (height, weight and waist circumference), blood pressure, fasting
      plasma glucose, and serum lipids (HDL-cholesterol and triglycerides) were
      measured. WHO cut-offs were used to define CVD risk factors. Food intake and
      physical activity were assessed with three non-consecutive 24-hour recalls.
      Information on tobacco use and alcohol consumption was collected using a
      questionnaire. An overall lifestyle score (OLS) was created based on diet
      quality, alcohol consumption, smoking, and physical activity. A SES score was
      computed based on education, main occupation and household amenities (as proxy
      for income). RESULTS: The most prevalent CVD risk factors were overall obesity
      (18%), abdominal obesity (32%), hypertension (23%), and low HDL-cholesterol
      (13%). Diabetes and hypertriglyceridemia were uncommon. The prevalence of overall
      obesity was roughly four times higher in women than in men (28 vs. 8%). After
      controlling for age and sex, the odds of obesity increased significantly with
      SES, while a longer exposure to the urban environment was associated with higher
      odds of hypertension. Of the single lifestyle factors examined, physical activity
      was the most strongly associated with several CVD risk factors. Logistic
      regression analyses revealed that the likelihood of obesity and hypertension
      decreased significantly as the OLS improved, while controlling for potential
      confounding factors. CONCLUSION: Our data show that obesity and cardio-metabolic
      risk factors are highly prevalent among urban adults in Benin, which calls for
      urgent measures to avert the rise of diet-related chronic diseases. People with
      higher SES and those with a longer exposure to the urban environment are priority
      target groups for interventions focusing on environmental risk factors that are
      amenable to change in this population. Lifestyle interventions would appear
      appropriate, with particular emphasis on physical activity.

PMID- 18318908
TI  - Goldsurfer2 (Gs2): a comprehensive tool for the analysis and visualization of
      genome wide association studies.
AB  - BACKGROUND: Genome wide association (GWA) studies are now being widely undertaken
      aiming to find the link between genetic variations and common diseases. Ideally,
      a well-powered GWA study will involve the measurement of hundreds of thousands of
      single nucleotide polymorphisms (SNPs) in thousands of individuals. The sheer
      volume of data generated by these experiments creates very high analytical
      demands. There are a number of important steps during the analysis of such data,
      many of which may present severe bottlenecks. The data need to be imported and
      reviewed to perform initial quality control (QC) before proceeding to association
      testing. Evaluation of results may involve further statistical analysis, such as
      permutation testing, or further QC of associated markers, for example, reviewing
      raw genotyping intensities. Finally significant associations need to be
      prioritised using functional and biological interpretation methods, browsing
      available biological annotation, pathway information and patterns of linkage
      disequilibrium (LD). RESULTS: We have developed an interactive and user-friendly
      graphical application to be used in all steps in GWA projects from initial data
      QC and analysis to biological evaluation and validation of results. The program
      is implemented in Java and can be used on all platforms. CONCLUSION: Very large
      data sets (e.g. 500 k markers and 5000 samples) can be quality assessed, rapidly
      analysed and integrated with genomic sequence information. Candidate SNPs can be
      selected and functionally evaluated.

PMID- 18318909
TI  - Information transfer in signaling pathways: a study using coupled simulated and
      experimental data.
AB  - BACKGROUND: The topology of signaling cascades has been studied in quite some
      detail. However, how information is processed exactly is still relatively
      unknown. Since quite diverse information has to be transported by one and the
      same signaling cascade (e.g. in case of different agonists), it is clear that the
      underlying mechanism is more complex than a simple binary switch which relies on
      the mere presence or absence of a particular species. Therefore, finding means to
      analyze the information transferred will help in deciphering how information is
      processed exactly in the cell. Using the information-theoretic measure transfer
      entropy, we studied the properties of information transfer in an example case,
      namely calcium signaling under different cellular conditions. Transfer entropy is
      an asymmetric and dynamic measure of the dependence of two (nonlinear) stochastic
      processes. We used calcium signaling since it is a well-studied example of
      complex cellular signaling. It has been suggested that specific information is
      encoded in the amplitude, frequency and waveform of the oscillatory Ca(2+)
      signal. RESULTS: We set up a computational framework to study information
      transfer, e.g. for calcium signaling at different levels of activation and
      different particle numbers in the system. We stochastically coupled simulated and
      experimentally measured calcium signals to simulated target proteins and used
      kernel density methods to estimate the transfer entropy from these bivariate time
      series. We found that, most of the time, the transfer entropy increases with
      increasing particle numbers. In systems with only few particles, faithful
      information transfer is hampered by random fluctuations. The transfer entropy
      also seems to be slightly correlated to the complexity (spiking, bursting or
      irregular oscillations) of the signal. Finally, we discuss a number of
      peculiarities of our approach in detail. CONCLUSION: This study presents the
      first application of transfer entropy to biochemical signaling pathways. We could
      quantify the information transferred from simulated/experimentally measured
      calcium signals to a target enzyme under different cellular conditions. Our
      approach, comprising stochastic coupling and using the information-theoretic
      measure transfer entropy, could also be a valuable tool for the analysis of other
      signaling pathways.

PMID- 18318910
TI  - Effects of acute and 14-day coenzyme Q10 supplementation on exercise performance
      in both trained and untrained individuals.
AB  - BACKGROUND: To determine whether acute (single dose) and/or chronic (14-days)
      supplementation of CoQ10 will improve anaerobic and/or aerobic exercise
      performance by increasing plasma and muscle CoQ10 concentrations within trained
      and untrained individuals. METHODS: Twenty-two aerobically trained and nineteen
      untrained male and female subjects (26.1 +/- 7.6 yrs, 172 +/- 8.7 cm, 73.5 +/- 17
      kg, and 21.2 +/- 7.0%) were randomized to ingest in a double-blind manner either
      100 mg of a dextrose placebo (CON) or a fast-melt CoQ10 supplement (CoQ10) twice
      a day for 14-days. On the first day of supplementation, subjects donated fasting
      blood samples and a muscle biopsy. Subjects were then given 200 mg of the placebo
      or the CoQ10 supplement. Sixty minutes following supplement ingestion, subjects
      completed an isokinetic knee extension endurance test, a 30-second wingate
      anaerobic capacity test, and a maximal cardiopulmonary graded exercise test
      interspersed with 30-minutes of recovery. Additional blood samples were taken
      immediately following each exercise test and a second muscle biopsy sample was
      taken following the final exercise test. Subjects consumed twice daily (morning
      and night), 100 mg of either supplement for a period of 14-days, and then
      returned to the lab to complete the same battery of tests. Data was analyzed
      using repeated measures ANOVA with an alpha of 0.05. RESULTS: Plasma CoQ10 levels
      were significantly increased following 2 weeks of CoQ10 supplementation (p <
      0.001); while a trend for higher muscle CoQ10 levels was observed after acute
      CoQ10 ingestion (p = 0.098). A trend for lower serum superoxide dismutase (SOD)
      was observed following acute supplementation with CoQ10 (p = 0.06), whereas serum
      malondialdehyde (MDA) tended to be significantly higher (p < 0.05). Following
      acute ingestion of CoQ10, plasma CoQ10 levels were significantly correlated to
      muscle CoQ10 levels; maximal oxygen consumption; and treadmill time to
      exhaustion. A trend for increased time to exhaustion was observed following 2
      weeks of CoQ10 supplementation (p = 0.06). CONCLUSION: Acute supplementation with
      CoQ10 resulted in higher muscle CoQ10 concentration, lower serum SOD oxidative
      stress, and higher MDA levels during and following exercise. Chronic CoQ10
      supplementation increased plasma CoQ10 concentrations and tended to increase time
      to exhaustion. Results indicate that acute and chronic supplementation of CoQ10
      may affect acute and/or chronic responses to various types of exercise.

PMID- 18318911
TI  - Association of Epstein-Barr virus antibody titers with a human IL-10 promoter
      polymorphism in Japanese women.
AB  - BACKGROUND: Multiple sclerosis (MS) risk, over 10-fold higher in Western than in
      Asian countries, is associated with elevated IgG antibody titers against Epstein
      Barr viral capcid antigen (anti-EBVCA IgG titers). Given the 84% homology of the
      open reading frame BCRF1 of Epstein-Barr virus (EBV) to human interleukin 10 (hIL
      10) and the remarkable Caucasian-vs.-Asian population differences in hIL-10 gene
      promoter polymorphisms, this strong association of MS risk with anti-EB-VCA IgG
      titers may be explained by the genetic variations in the hIL-10 gene. METHODS: We
      evaluated anti-EB-VCA IgG titers in association with a single nucleotide
      polymorphism (SNP) in the promoter of hIL-10 at position -819 (hIL-10 T-819C) in
      a cross-sectional survey of 241 Japanese. Anti-EB-VCA IgG titer and its elevation
      (> or = 1:160) were evaluated, stratified by sex and hIL-10 T-819C genotype.
      RESULTS: The cytosine-allele frequencies at hIL-10 T-819C were 32.9% in women and
      30.9% in men. These are consistent with the published reports of Japanese and
      Chinese, but substantially lower than those of Caucasians (> 70%). In women, the
      proportion with elevated anti-EB-VCA IgG titers (> or = 1:160) increased
      appreciably from 53.7% in the T/T genotype group to 66.7% in the T/C group and to
      83.3% in the C/C group (P-trend = 0.037). The titers did not differ by the hIL-10
      T-819C genotype in men. CONCLUSION: Anti-EB-VCA IgG titers may increase with the
      number of cytosine alleles at hIL-10 T-819C in women. This observed gender
      specific association in Japanese warrants further investigation, especially in
      Western populations with high MS risk.

PMID- 18318912
TI  - Variability in prescription drug expenditures explained by adjusted clinical
      groups (ACG) case-mix: a cross-sectional study of patient electronic records in
      primary care.
AB  - BACKGROUND: In view of rapidly increasing prescription costs, case-mix adjustment
      should be considered for effective control of costs. We have estimated the
      variability in pharmacy costs explained by ACG in centers using patient
      electronic records, profiled centers and physicians and analyzed the correlation
      between cost and quality of prescription. METHODS: We analyzed 65,630 patient
      records attending five primary care centers in Spain during 2005. Variables
      explored were age, gender, registered diagnosed episodes of care during 2005,
      total cost of prescriptions, physician and center. One ACG was assigned to each
      patient with ACG case-mix software version 7.1. In a two-part model, logistic
      regression was used to explain the incurrence of drug expenditure at the first
      stage and a linear mixed model that considered the multilevel structure of data
      modeled the cost, conditional upon incurring any expense. Risk and efficiency
      indexes in pharmacy cost adjusted for ACG were obtained for centers and
      physicians. Spearman rank correlation between physician expenditure, adjusted for
      ACG, and a prescription quality index was also obtained. Pediatric and adult data
      were analyzed separately. RESULTS: No prescription was recorded for 13% of adults
      and 39.6% of children. The proportion of variance of the incurrence of
      expenditure explained by ACGs was 0.29 in adults and 0.21 in children. For adults
      with prescriptions, the variance of cost explained by ACGs was 35.4%, by
      physician-center was 1.8% and age 10.5% (residual 52.3%). For children, ACGs
      explained 22.4% of cost and physician-center 10.9% (residual 66.7%). Center
      efficiency index for adults ranged 0.58 to 1.22 and for children 0.32 to 2.36.
      Spearman correlation between expenditure and prescription quality index was -0.36
      in family physicians (p = 0.019, N = 41) and -0.52 in pediatricians (p = 0.08, N
      = 12). CONCLUSION: In our setting, ACG is the variable studied that explains more
      variability in pharmacy cost in adults compared to physician and center. In
      children there is greater variability among physicians and centers not related to
      case-mix. In our sites, ACG is useful to profile physicians and centers using
      electronic records in real practical conditions. Physicians with lower
      pharmaceutical expenditure have higher scores for a prescription quality index.

PMID- 18318913
TI  - Analysis of tall fescue ESTs representing different abiotic stresses, tissue
      types and developmental stages.
AB  - BACKGROUND: Tall fescue (Festuca arundinacea Schreb) is a major cool season
      forage and turf grass species grown in the temperate regions of the world. In
      this paper we report the generation of a tall fescue expressed sequence tag (EST)
      database developed from nine cDNA libraries representing tissues from different
      plant organs, developmental stages, and abiotic stress factors. The results of
      inter-library and library-specific in silico expression analyses of these ESTs
      are also reported. RESULTS: A total of 41,516 ESTs were generated from nine cDNA
      libraries of tall fescue representing tissues from different plant organs,
      developmental stages, and abiotic stress conditions. The Festuca Gene Index
      (FaGI) has been established. To date, this represents the first publicly
      available tall fescue EST database. In silico gene expression studies using these
      ESTs were performed to understand stress responses in tall fescue. A large number
      of ESTs of known stress response gene were identified from stressed tissue
      libraries. These ESTs represent gene homologues of heat-shock and oxidative
      stress proteins, and various transcription factor protein families. Highly
      expressed ESTs representing genes of unknown functions were also identified in
      the stressed tissue libraries. CONCLUSION: FaGI provides a useful resource for
      genomics studies of tall fescue and other closely related forage and turf grass
      species. Comparative genomic analyses between tall fescue and other grass
      species, including ryegrasses (Lolium sp.), meadow fescue (F. pratensis) and
      tetraploid fescue (F. arundinacea var glaucescens) will benefit from this
      database. These ESTs are an excellent resource for the development of simple
      sequence repeat (SSR) and single nucleotide polymorphism (SNP) PCR-based
      molecular markers.

PMID- 18318914
TI  - Coexistence of carcinoma and tuberculosis in one breast.
AB  - BACKGROUND: The coexistence of breast cancer and tuberculosis is very rare. This
      can create a dilemma in the diagnosis and treatment as there are no pathognomonic
      symptoms or signs to distinguish both diseases. CASE PRESENTATION: A female
      patient was seen in the breast clinic for a right breast lump. Clinical
      examination and investigation confirmed cancer and tuberculosis of the right
      breast. She underwent right mastectomy and axillary clearance and received chemo
      and radiotherapy. Unfortunately, she died of wide spread metastases. CONCLUSION:
      The simultaneous occurrence of these two major illnesses in the breast can lead
      to many problems regarding diagnosis and treatment. Though rare, surgeons,
      pathologists and radiologists should be aware of such condition.

PMID- 18318915
TI  - Detecting myocardial infarction in critical illness using screening troponin
      measurements and ECG recordings.
AB  - INTRODUCTION: To use screening cardiac troponin (cTn) measurements and
      electrocardiograms (ECGs) to determine the incidence of elevated cTn and of
      myocardial infarction (MI) in patients admitted to the intensive care unit (ICU),
      and to assess whether these findings influence prognosis. This is a prospective
      screening study. MATERIALS AND METHODS: We enrolled consecutive patients admitted
      to a general medical-surgical ICU over two months. All patients underwent
      systematic screening with cTn measurements and ECGs on ICU admission, then daily
      for the first week in ICU, alternate days for up to one month and weekly
      thereafter until ICU death or discharge, for a maximum of two months. Patients
      without these investigations ordered during routine clinical care underwent
      screening for study purposes but these results were unavailable to the ICU team.
      After the study, all ECGs were interpreted independently in duplicate for
      ischaemic changes meeting ESC/ACC criteria supporting a diagnosis of MI. Patients
      were classified as having MI (elevated cTn and ECG evidence supporting diagnosis
      of MI), elevated cTn only (no ECG evidence supporting diagnosis of MI), or no cTn
      elevation. RESULTS: One hundred and three patients were admitted to the ICU on
      112 occasions. Overall, 37 patients (35.9 per cent) had an MI, 15 patients (14.6
      per cent) had an elevated cTn only and 51 patients (49.5 per cent) had no cTn
      elevation. Patients with MI had longer duration of mechanical ventilation (p <
      0.0001), longer ICU stay (p = 0.001), higher ICU mortality (p < 0.0001) and
      higher hospital mortality (p < 0.0001) compared with those with no cTn elevation.
      Patients with elevated cTn had higher hospital mortality (p = 0.001) than
      patients without cTn elevation. Elevated cTn was associated with increased
      hospital mortality (odds ratio 27.3, 95 per cent CI 1.7 - 449.4), after adjusting
      for APACHE II score, MI and advanced life support. The ICU team diagnosed 18
      patients (17.5 per cent) as having MI on clinical grounds; four of these patients
      did not have MI by adjudication. Thus, screening detected an additional 23 MIs
      not diagnosed in practice, reflecting 62.2 per cent of MIs ultimately diagnosed.
      Patients with MI diagnosed by the ICU team had similar outcomes to patients with
      MI detected by screening alone. CONCLUSION: Systematic screening detected
      elevated cTn measurements and MI in more patients than were found in routine
      practice. Elevated cTn was an independent predictor of hospital mortality.
      Further research is needed to evaluate whether screening and subsequent treatment
      of these patients reduces mortality.

PMID- 18318916
TI  - Extensive necrosis of visceral melanoma metastases after immunotherapy.
AB  - BACKGROUND: The prognosis for metastatic melanoma remains poor even with
      traditional decarbazine or interferon therapy. 5-year survival is markedly higher
      amongst patients undergoing metastatectomy. Unfortunately not all are suitable
      for metastatectomy. Alternative agents for systemic therapy have, to date,
      offered no greater rates of survival beyond traditional therapy. A toll-like
      receptor 9 agonist, PF-3512676 (formerly known as CPG 7909) is currently being
      evaluated for its potential. CASE PRESENTATION: We present the case of a 54-year
      old Caucasian male with completely resected metastatic cutaneous melanoma after
      immunotherapy. The patient initially progressed during adjuvant high-dose
      interferon, with metastases to the liver, spleen, and pelvic lymph nodes. During
      an 18-month treatment period with PF-3512676 (formerly known as CPG 7909), a
      synthetic cytosine-phosphorothioate-guanine rich oligodeoxynucleotide, slow
      radiologic disease progression was demonstrated at the original disease sites.
      Subsequent excision of splenic and pelvic nodal metastases was performed,
      followed by resection of the liver metastases. Histologic examination of both
      hepatic and splenic melanoma metastases showed extensive necrosis. Subsequent
      disease-free status was demonstrated by serial positron emission tomography
      (PET). CONCLUSION: Existing evidence from phase I/II trials suggests systemic
      treatment with PF-3512676 is capable of provoking a strong tumor-specific immune
      response and may account for the prolonged tumor control in this instance.

PMID- 18318917
TI  - Normalization of oligonucleotide arrays based on the least-variant set of genes.
AB  - BACKGROUND: It is well known that the normalization step of microarray data makes
      a difference in the downstream analysis. All normalization methods rely on
      certain assumptions, so differences in results can be traced to different
      sensitivities to violation of the assumptions. Illustrating the lack of
      robustness, in a striking spike-in experiment all existing normalization methods
      fail because of an imbalance between up- and down-regulated genes. This means it
      is still important to develop a normalization method that is robust against
      violation of the standard assumptions RESULTS: We develop a new algorithm based
      on identification of the least-variant set (LVS) of genes across the arrays. The
      array-to-array variation is evaluated in the robust linear model fit of pre
      normalized probe-level data. The genes are then used as a reference set for a non
      linear normalization. The method is applicable to any existing expression
      summaries, such as MAS5 or RMA. CONCLUSION: We show that LVS normalization
      outperforms other normalization methods when the standard assumptions are not
      satisfied. In the complex spike-in study, LVS performs similarly to the ideal (in
      practice unknown) housekeeping-gene normalization. An R package called lvs is
      available in http://www.meb.ki.se/~yudpaw.

PMID- 18318918
TI  - Absence of contralateral suppression of transiently evoked otoacoustic emissions
      in fibromyalgia syndrome.
AB  - OBJECTIVE: To assess contralateral suppression of transiently evoked otoacoustic
      emissions in patients with fibromyalgia syndrome and normal hearing. METHODS:
      Twenty-four female patients with fibromyalgia syndrome and 24 healthy female
      controls with normal hearing were assessed using pure tone audiometry and
      transiently evoked otoacoustic emissions. RESULTS: All patients with fibromyalgia
      syndrome and all controls had normal hearing on pure tone audiometry. In the
      patients with fibromyalgia syndrome, the mean transiently evoked otoacoustic
      emission amplitude was 15.5 +/- 4.8 dB. The mean transiently evoked otoacoustic
      emission amplitudes after contralateral suppression was 15.5 +/- 4.9 dB. There
      was no statistically significant difference between the transiently evoked
      otoacoustic emission amplitudes measured before and after contralateral
      suppression (p > 0.05). In the controls, the mean transiently evoked otoacoustic
      emission amplitude was 12 +/- 5 dB. The mean transiently evoked otoacoustic
      emission amplitudes after contralateral suppression was 11 +/- 4.7 dB. There was
      a statistically significant decrease in transiently evoked otoacoustic emission
      amplitudes after contralateral suppression (p < 0.01). CONCLUSION: The mechanisms
      related to contralateral suppression of transiently evoked otoacoustic emissions
      seem dysfunctional in fibromyalgia syndrome. This dysfunction may be at the brain
      stem level, where the medial superior olivary complex is located, or at the
      synapses of medial superior olivary complex fibres with the outer hair cells in
      the cochlea. Demonstration of lack of contralateral suppression of transiently
      evoked otoacoustic emissions can be used as a diagnostic tool in patients with
      fibromyalgia syndrome.

PMID- 18318919
TI  - Re: secular trends in the epidemiology of shingles in Alberta.

PMID- 18318920
TI  - The JTT at 100.

PMID- 18318921
TI  - Mobile teledermatology: a feasibility study of 58 subjects using mobile phones.
AB  - We investigated the diagnostic agreement between teledermatology based on images
      from a mobile phone camera and face-to-face (FTF) dermatology. Diagnostic
      agreement was assessed for two teledermatologists (TD) in comparison with FTF
      consultations in 58 subjects. In almost three-quarters of the cases (TD1: 71%;
      TD2: 76%), the telediagnosis was fully concordant with the FTF diagnosis.
      Furthermore, the diagnosed diseases were almost all in the same diagnostic
      category (TD1: 97%; TD2: 90%). If mobile teledermatology had been used for remote
      triage, TD1 could have treated 53% subjects remotely and 47% subjects would have
      had to consult a dermatologist FTF. TD2 could have treated 59% subjects remotely,
      whereas 41% subjects would have had to consult a dermatologist FTF. Forty-eight
      subjects responded to a questionnaire, of whom only 10 had any concerns regarding
      teledermatology. Thirty-one subjects stated that they would be willing to pay to
      use a similar service in future and suggested an amount ranging from euro5 to
      euro50 per consultation (mean euro22) (euro = pound0.7, US $1.4). These results
      are encouraging as patient acceptance and reimbursement represent potential
      obstacles to the implementation of telemedicine services.

PMID- 18318922
TI  - An evaluation of second and third generation telecare services in older people's
      housing.
AB  - In a controlled study of older people living in sheltered housing (retirement
      housing), 24 people provided with telecare were compared with a control group of
      28 people. The intervention consisted of second generation telecare equipment,
      such as automatic flood or falls detectors, a third generation lifestyle
      reassurance system and an Internet cafe. After a 12-month monitoring period,
      there was no noticeable change in the fear of falling. There was no significant
      difference for eight of the nine SF-36 domains. However, the Social Functioning
      domain showed a significant difference (P = 0.049), with scores 8% higher in the
      intervention group, suggesting a beneficial effect of telecare. Positive trends
      were also evident in areas such as an increase in the length of time spent out of
      the home, improved feelings of safety during the day and night, and a reduction
      in the fear of crime. The Internet cafe was used by 25% of people for at least 20
      min per week. The results suggest that second generation telecare systems and
      Internet facilities could be more widely used in service delivery, but that
      lifestyle reassurance requires further development.

PMID- 18318923
TI  - Long-term treatment of obese children and adolescents using a telemedicine
      support programme.
AB  - A total of 140 obese patients (mean age 14 years) participated in a structured
      treatment and teaching programme (STTP) in hospital, with the aim of weight
      reduction. At both the start and finish of the STTP, patients underwent clinical
      and psychological examination. During an average hospital stay of 35 days, their
      mean bodyweight decreased from 82.4 kg to 76.0 kg (P < 0.001). Patients were then
      followed up with a telemedicine support programme. During the next 12 months, the
      acceptance of the telemedicine support programme declined from 93% to 46%. The
      body mass index was 30.5 kg/m(2) at admission and 27.7 kg/m(2) at 12-month follow
      up (P < 0.05). In parallel, wellbeing and treatment satisfaction increased, and
      there was a positive effect on eating behaviour and exercise. Intervention was
      needed in up to 64% of the children and adolescents who participated in the
      programme, most frequently due to poor results in exercise. Telemedical follow-up
      care and counselling seemed to be highly effective, and allowed not only an
      initial weight reduction, but long-term stabilization as well.

PMID- 18318924
TI  - The TeleGuard trial of additional telemedicine care in CAD patients. 1
      Utilization of the system.
AB  - Patients with established coronary artery disease (CAD) were recruited in 11
      hospitals and randomized to an intervention (telemedicine system; n = 752) or a
      control group (usual medical care; n = 748). On the day before discharge,
      patients in the intervention group were equipped with a 12-lead event recorder
      and trained to use the device. Whenever they had symptoms, they could contact the
      call centre, transmit an ECG (without redialling) and consult a physician. During
      a 12-month study, 171 patients (23%) in the intervention group contacted the call
      centre, a total of 269 times. The main reasons for calling were chest pain and
      radiating pain. Pathological changes were seen in 24% of the transmitted ECGs.
      Only 23% of the calls were made in the first hour after onset of symptoms and a
      further 12% in the subsequent hour, suggesting that patients should be encouraged
      to use ECG transmission at an earlier stage. At follow-up, 157 patients (21%) had
      had at least one recurrent cardiac event (myocardial infarction, cardiac hospital
      stay, re-vascularization). The proportion was significantly higher in
      telemedicine users (35%) than in non-users (17%), P < 0.001. Regardless of
      utilization, the majority of the intervention patients considered that the
      telemedicine system was helpful (users = 93%, non-users = 89%; P = 0.095).

PMID- 18318925
TI  - The TeleGuard trial of additional telemedicine care in CAD patients. 2 Morbidity
      and mortality after 12 months.
AB  - In the TeleGuard trial, 1500 patients with established coronary artery disease
      (CAD) were recruited and randomized to control or intervention groups. Patients
      in the intervention group were equipped with a 12-lead event recorder and could
      contact a call centre and transmit an ECG whenever they wished. In a 12-month
      study, the composite endpoint (all-cause mortality, myocardial infarction, re
      hospitalization or re-vascularization) was seen in 40% of the intervention
      patients and in 38% of the control patients. In both groups, approximately 40%
      were re-hospitalized. In total, 73 patients experienced re-vascularization, 75
      showed an infarction and 33 died. Equipping CAD patients with a 12-lead ECG
      device and providing a telemedicine centre with 24-hour availability did not
      decrease risk for the composite endpoint (re-hospitalization, re-vascularization,
      (subsequent) myocardial infarction and/or death). It is likely that the clinical
      pathway used in the telemedicine centre led to an increased hospital admission
      rate in the intervention group.

PMID- 18318926
TI  - The potential of digital monochrome images versus colour slides in telescreening
      for diabetic retinopathy.
AB  - We explored the potential of digital monochrome images as an alternative to
      colour slides in screening for diabetic retinopathy. Twenty-eight patients with
      diabetes were recruited for the study and 20 actually participated. Using a
      fundus camera (Nikon 505AF) one set of three digital images and one set of three
      colour slides were taken per eye. Two independent ophthalmologists graded the
      colour slides and the digital images for diabetic retinopathy. The
      ophthalmologists spent about two minutes grading each set of images, suggesting
      that specialists could potentially screen a large number of patients. The
      agreement between the two screening methods was 0.95 and 0.89, with respect to
      disease or no disease. The agreement (kappa) between the two ophthalmologists for
      grade of retinopathy was 0.47 when colour slides were employed and 0.61 when
      digital monochrome images were employed. The results indicate that digital red
      free monochrome images represent a superior screening tool for diabetic
      retinopathy. Tele-screening may be beneficial when patients have to travel
      substantial distances to visit an ophthalmologist.

PMID- 18318927
TI  - Automated telephone reminder messages can assist electronic diabetes care.
AB  - Telephone reminder systems have been used to assist in the treatment of many
      chronic diseases. However, it is unclear if these systems can increase medication
      and appointment adherence in patients with diabetes without direct patient
      provider telephone contact. We tested the feasibility of using an automated
      telephone reminder system (ATRS) to deliver reminder messages to 253 adults with
      diabetes enrolled in a randomized controlled trial. Eighty-four percent of the
      patients were able to register using voice recognition and at least one reminder
      was delivered to 95% of registered patients over a period of 7.5 months. None of
      the demographic features studied predicted a patient's ability to enroll or to
      receive reminder calls. At the end of the study, 63% of patients indicated that
      they wished to continue to receive ATRS calls. The level of system use as
      determined by the number of received reminder calls was not associated with a
      change in the number of physician visits or diabetes-related laboratory tests
      during follow-up. The clinical benefits and sustainability of ATRS remain
      unproven, but our results indicate that an automated reminder system can be
      effective for providing messages to a large group of older patients with
      diabetes.

PMID- 18318928
TI  - A review of ICT systems for HIV/AIDS and anti-retroviral treatment management in
      South Africa.
AB  - Telemedicine and e-health systems have been proposed as a support tool, to
      monitor and evaluate HIV/AIDS management strategies. The aim of the present study
      was to provide an overview of telemedicine and e-health systems for HIV/AIDS in
      South Africa as a basis for developing an e-health toolkit for anti-retroviral
      treatment (ART). An initial literature review and a subsequent interactive
      networking approach were chosen to identify telemedicine and e-health systems,
      projects and services for HIV/AIDS and ART facilities in low-resource settings
      and under-served areas. The literature review produced little useful information.
      In contrast, the face-to-face interviews and the focus group discussions provided
      useful information about projects and systems which had not been published. The
      meetings involved 1 - 5 people per session, about 30 people in total. The review
      showed that there were some plans for telemedicine and e-health implementation in
      South Africa. However, there was no all-inclusive ICT-based system in place for
      AIDS treatment there. With the exception of the major health information systems
      and electronic patient record systems, none of the telemedicine and e-health
      systems identified in the review were ready to be deployed across the country as
      a whole.

PMID- 18318929
TI  - Mental health profile of callers to a telephone counselling service.
AB  - We studied the mental health profile of callers to a generalist helpline. A
      survey was conducted in a large telephone counselling centre over a four-week
      period in 2006. Telephone counsellors administered the survey at the completion
      of a user's call. The centre answered a total of 1404 calls in the study period.
      Of these, 439 calls met the inclusion criteria and 270 callers agreed to
      participate. The survey collected data from callers on demographic variables,
      anxiety, depression, panic and social phobia, alcohol use, frequency of help
      seeking from the service, sources of professional help, attitudes to help
      services and access to the Internet. Callers experienced high levels of anxiety
      and depression. More frequent callers were older, with very frequent callers more
      likely to be never married. More frequent callers were more likely to report
      concerns with loneliness, physical illness and anxiety. There was a significant
      difference on the Goldberg Anxiety Scale (P < 0.05), with more frequent callers
      having higher anxiety scores. However, there was no significant difference on the
      Goldberg depression scores as a function of call frequency (P > 0.05). Panic
      attacks were more common among more frequent callers. These results will be
      useful in developing new telephone-administered anxiety and depression treatment
      programmes.

PMID- 18318930
TI  - Memorable telemedicine experiences.

PMID- 18318931
TI  - Complexity of the msp2 locus and the severity of childhood malaria, in south
      western Nigeria.
AB  - As the genetic diversity of Plasmodium falciparum infections in humans is
      implicated in the pathogenesis of malaria, the association between P. falciparum
      diversity at the merozoite surface protein-2 (msp2) locus and the severity of
      childhood malaria was investigated in Ibadan, in south-western Nigeria. The 400
      children enrolled had acute uncomplicated malaria (144), cerebral malaria (64),
      severe malarial anaemia (67) or asymptomatic infections with P. falciparum (125).
      Nested PCR was used to investigate the msp2 genotype(s) of the parasites
      infecting each child. In terms of the complexity of infection and frequency of
      polyinfection, the children with asymptomatic infection were significantly
      different from those with uncomplicated malaria or severe malaria. The median
      number of FC27 alleles detected was higher in the asymptomatic children than in
      the symptomatic. After controlling for age and level of parasitaemia (with
      'asymptomatic infection' as the reference category), a child in whom no FC27
      alleles were detected was found to be at five-fold greater risk of uncomplicated
      malaria, and a child without polyinfection was found to have a three-fold
      increased risk of severe malarial anaemia and a six-fold increased risk of
      cerebral malaria. It therefore appears that msp2 genotypes are associated with
      asymptomatic carriage and that children with mono-infections are more likely to
      develop severe malaria than children with polyinfection.

PMID- 18318932
TI  - Febrile status, malarial parasitaemia and gastro-intestinal helminthiases in
      schoolchildren resident at different altitudes, in south-western Cameroon.
AB  - In the many areas where human malaria and helminthiases are co-endemic,
      schoolchildren often harbour the heaviest infections and suffer much of the
      associated morbidity, especially when co-infected. In one such area, the Buea
      district, in south-western Cameroon, two cross-sectional surveys, together
      covering 263 apparently healthy schoolchildren aged 4-12 years, were recently
      conducted. The prevalences of fever, malarial parasitaemia and intestinal
      helminth infections, the seroprevalences of anti-Plasmodium falciparum IgG and
      IgE and anti-glycosylphosphatidylinositol (anti-GPI) IgG, plasma concentrations
      of total IgE, and the incidence of anaemia were all investigated. The mean (S.D.)
      age of the study children was 7.56 (1.82) years. Overall, 156 (59.3%) of the
      children were found parasitaemic, with a geometric mean parasitaemia of 565
      parasites/microl. Parasitaemia and fever were significantly associated (P=0.042).
      The children who lived at low altitude, attending schools that lay 400-650 m
      above sea level, had significantly higher parasitaemias than their high-altitude
      counterparts (P<0.01). At low altitude, the children attending government schools
      had significantly higher parasitaemias than their mission-school counterparts
      (P=0.010). Of the 31 children (11.9%) found anaemic, 22 (70.4%) had mild anaemia
      and none had severe anaemia. A significant negative correlation (r=-0.224;
      P=0.005) was observed between haemoglobin concentration and level of
      parasitaemia. Infection with Plasmodium appeared to reduce erythrocyte counts
      (P=0.045), a condition that was exacerbated by co-infection with helminths
      (P=0.035). Plasma concentrations of total IgE were higher in the children found
      to be excreting helminth eggs than in those who appeared helminth-free, while
      levels of anti-P. falciparum IgE were higher in the children with low-grade
      parasitaemias than in those with more intense parasitaemias. Levels of anti-GPI
      IgG increased with age and were relatively high in the children who lived at low
      altitude and in those who were aparasitaemic. The survey results confirm that
      asymptomatic malarial parasitaemia frequently co-exists with helminth infections
      in schoolchildren and indicate links with fever, altitude and school type.
      Immunoglobulin E may play a role in immune protection against helminthiasis
      whereas anti-GPI antibodies may be important in the development of antimalarial
      immunity in such children. In Cameroon, as in other areas with endemic malaria,
      control programmes to reduce the prevalences of infections with intestinal
      helminths and malarial parasites in schoolchildren, which may effectively reduce
      the incidence of anaemia, are clearly needed.

PMID- 18318933
TI  - A community-based, comparative evaluation of direct agglutination and rK39 strip
      tests in the early detection of subclinical Leishmania donovani infection.
AB  - In the Indian state of Bihar, the sensitivities and specificities of direct
      agglutination tests (DAT) and rK39 test strips for the detection of Leishmania
      donovani infection in humans were explored and found to be generally good (92%
      100%). When 172 asymptomatic individuals [16 'case-contacts' who lived in the
      same households as past or current, confirmed cases of visceral leishmaniasis
      (VL) and 156 other subjects from neighbouring households] were tested, the same
      36 (21%) individuals, including all 16 'case-contacts', were found seropositive
      using each type of test. When followed-up after 3 months, 18 of the individuals
      who had been found seropositive in the baseline survey remained seropositive, and
      eight (44%) of these had developed symptomatic VL, with amastigotes in their
      splenic aspirates. Seven (44%) of the 16 'case-contacts' but only one (5%) of the
      other 20 subjects found seropositive at baseline went on to develop VL within 3
      months. Although the strip test appeared slightly better than DAT for predicting
      the development of VL in the 172 subjects, either type of test may be very useful
      for the early detection of asymptomatic L. donovani infection and thus the
      identification of those at relatively high risk of developing VL.

PMID- 18318934
TI  - Rodent infection with Leishmania in a new focus of human cutaneous leishmaniasis,
      in northern Iran.
AB  - The incidence of zoonotic cutaneous leishmaniasis (ZCL), which is endemic in
      several parts of Iran, has recently increased in the rural areas of the northern
      district of Damghan, in Semnan province. Between 2001 and 2004, as part of an
      investigation of this worrying trend, wild rodents in this region were caught and
      checked, by the microscopical examination of liver and spleen smears, for
      leishmanial infection, to see which species were acting as 'reservoir' hosts.
      Overall 298 Nesokia indica, 29 Meriones libycus, 10 Mus musculus and two Microtus
      socialis were caught. Most of the N. indica (61%) and Me. libycus (52%) but none
      of the other rodents were found smear-positive for leishmanial amastigotes. When
      PCR was used to test scrapings from 50 of the smears (of which 25 had been found
      to harbour amastigotes, by microscopy), 29 (58%) of the smears were found
      positive for the kinetoplast DNA of Leishmania major; none was found positive for
      any other Leishmania species. Nesokia indica and Me. libycus are therefore
      incriminated as the main 'reservoir' hosts of L. major in Damghan.

PMID- 18318935
TI  - Prevention of lymphatic filariasis with insecticide-treated bednets in Cambodia.
AB  - Potential risk factors for lymphatic filariasis (LF), including the failure to
      use insecticide-treated bednets (ITN), were studied in four north-eastern
      provinces of Cambodia, using 43 cases of LF and 248 apparently healthy controls
      who were matched with the cases in terms of age (+/-5 years), gender and village.
      The results of a univariate matched analysis indicated that lack of ITN [odds
      ratio (OR)=20.1; 95% confidence interval (CI)=2.2-182.4; P=0.008] and frequent
      overnight stays in forests or paddy fields outside the village (OR=3.6; CI=1.3
      10.0; P=0.012) were the most important risk factors. In a multivariate matched
      analysis, frequent overnight stays outside the village combined with bednet use
      showed a clear dose-response relationship, with untreated nets offering
      significant protection during such stays but ITN offering significantly better
      protection. Even if villagers used ITN during such stays, they were significantly
      more likely to develop LF than villagers who did not travel (OR=5.0; CI=1.5-16.3;
      P=0.008), and if they used untreated or no nets while away they were even more
      likely than the non-travellers to develop the disease (OR=1413; CI=28.0-71,189;
      P<0.001). Taken together, these results provide further evidence for the
      importance of bednet use and their impregnation in the prevention of LF. At least
      in north-eastern Cambodia, the use of bednets and, preferably, ITN is
      particularly important during overnight stays outside the home village. In areas
      where LF is endemic, the sustained distribution of insecticide-treated bednets or
      hammock nets appears to be a very good idea.

PMID- 18318936
TI  - Comparative efficacies of albendazole and the Chinese herbal medicine long-dan
      xie-gan-tan, used alone or in combination, in the treatment of experimental
      eosinophilic meningitis induced by Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis, the rat lungworm, is the principal cause of human
      eosinophilic meningitis or meningoencephalitis world-wide. In the present study,
      the efficacies of early-stage treatment with the Chinese herbal medicine long-dan
      xie-gan-tan (LDXGT) and albendazole, used alone or in combination, were evaluated
      in BALB/c mice with A. cantonensis-induced dysfunction of the blood-central
      nervous-system barrier and eosinophilic meningo-encephalitis. Indicators of the
      therapeutic effect included worm recovery, histopathological scores for the
      meningitis, assays of tissue-type plasminogen activator (PA), urokinase-type PA
      and matrix metalloproteinase-9 (MMP-9) in the brain, the ratio between albumin
      concentrations in the cerebrospinal fluid (CSF) and serum, and counts of
      eosinophils in the CSF. Combined treatment with albendazole and LDXGT gave better
      results than monotherapy based on either drug, apparently inhibiting eosinophilic
      meningitis via antagonists of the PA/MMP-9 system. LDXGT may have a therapeutic
      role in reducing inflammatory reaction in the subarachnoid space. Monotherapy
      with such an anti-inflammatory drug may relieve the symptoms of mild infection
      and the host's immune responses to A. cantonensis larvae. In severe infection,
      however, co-therapy with an anthelmintic (to kill the larvae) and an anti
      inflammatory agent (to provide symptomatic relief) is probably a better approach.
      The therapeutic strategy should be tailored to the severity of the illness and
      the numbers of eosinophils in the CSF.

PMID- 18318937
TI  - rTES-30USM: cloning via assembly PCR, expression, and evaluation of usefulness in
      the detection of toxocariasis.
AB  - Currently, the laboratory diagnosis of toxocariasis, caused by Toxocara canis or
      T. cati, mainly relies on serological tests. Unfortunately, however, the
      specificities of most of the commercial tests that are available for the
      serodiagnosis of this disease are not very high and this may cause problems,
      especially in tropical countries where co-infections with other helminths are
      common. In an effort to develop a serological assay with improved specificity for
      the detection of Toxocara infection, an IgG(4)-ELISA based on a recombinant
      version (rTES-30USM) of the 30-kDa Toxocara excretory-secretory antigen (TES-30)
      has recently been developed. To produce the antigen, the TES-30 gene was cloned
      via assembly PCR, subcloned into a His-tagged prokaryotic expression vector, and
      purified by affinity chromatography using Ni(2+)-nitrilotriacetic-acid (Ni-NTA)
      resin. The performance of the ELISA based on the recombinant antigen was then
      compared with that of commercial kit, based on an IgG-ELISA, for the
      serodiagnosis of toxocariasis (Toxocara IgG-ELISA; Cypress Diagnostics, Langdorp,
      Belgium). Both assays were used to test 338 serum samples, including 26 samples
      from probable cases of toxocariasis. Assuming that all the probable cases were
      true cases, the assay based on rTES-30USM demonstrated a sensitivity of 92.3%
      (24/26) and a specificity of 89.6% (103/115) whereas the commercial kit exhibited
      a sensitivity of 100% (26/26) but a specificity of only 55.7% (64/115). The high
      sensitivity and specificity exhibited by the new IgG(4)-ELISA should make the
      assay a good choice for use in tropical countries and any other area where
      potentially cross-reactive helminthic infections are common.

PMID- 18318938
TI  - Assessment of a new strategy, based on Aedes aegypti (L.) pupal productivity, for
      the surveillance and control of dengue transmission in Thailand.
AB  - In the countries where the disease is endemic, control of dengue is mainly based
      on the elimination or treatment of the water-filled containers where the main
      vector, Aedes aegypti, breeds, in interventions usually reliant on community
      participation. Although such control activities must be continuous, since vector
      eradication appears impossible, it should be possible to reduce the incidence of
      dengue significantly, in a cost-effective manner, by targeting only those types
      of containers in which large numbers of Ae. aegypti are produced. This strategy
      is now recommended by the World Health Organization, although it depends on the
      most productive types of container being carefully identified, in each endemic
      region. In Thailand, exhaustive surveys of 3125 wet containers in 240 houses in
      either an urban area (100-120 houses) or a rural area (120 houses) were conducted
      during a rainy and a dry season in 2004-2005. Indices based on the numbers of Ae.
      aegypti pupae observed were found to correlate with the 'classical' entomological
      indices that are based on all of the immature stages of the vector. Overall, 2.3
      and 0.8 Ae. aegypti pupae were observed per person in the rural and urban areas,
      respectively. Although adult female Ae. aegypti laid eggs in all 10 types of wet
      container that were identified, large water-storage containers produced the
      majority of the pupae, especially at the end of the dry season (when such
      containers accounted for 90% of the pupae detected in the rural area and 60% of
      those in the urban area). Since these containers are large, easy to reach and
      account for, <50% of all wet containers, it should be relatively easy and quick
      to treat them with larvicide or to cover them. If even such targeted treatment is
      to be sustainable, however, it will have to be integrated, as one of several
      activities in which the at-risk communities are encouraged to participate.

PMID- 18318939
TI  - Efficacy of RPMI 1640 and M 199 media in the isolation of Leishmania from
      cutaneous lesions.

PMID- 18318940
TI  - Triple drug administration (TDA), with praziquantel, ivermectin and albendazole,
      for the prevention of three neglected tropical diseases in Nigeria.

PMID- 18318941
TI  - Antimalarial activity of a stilbene glycoside from Pleuropterus ciliinervis.

PMID- 18318942
TI  - HIV infection, visceral leishmaniasis and Guillain-Barre syndrome in the same
      patient: a case report.

PMID- 18318944
TI  - Diagnosis of pulmonary tuberculosis in young children.
AB  - The Stop TB Strategy encompasses promotion and support for childhood TB including
      diagnosis. The diagnosis of TB in low-income countries needs to be improved using
      existing technology. All hospitals involved in managing children with TB should
      have a regular stock of tuberculin. A chest radiograph (CXR) is an integral part
      of the diagnosis of pulmonary TB and hospitals should be able to take
      satisfactory CXRs of young children. If there is a reliable laboratory service,
      bacterial confirmation should be undertaken in selected cases. The laboratory
      should be able to deal satisfactorily with paediatric specimens. Gastric
      aspiration is the method of choice to obtain sputum from young children and
      generally produces higher yields than other methods, and, with good technique,
      results in outpatients may not be much lower than in inpatients. Nasopharyngeal
      aspiration is a simple alternative method requiring limited equipment. Sputum
      induction requires a special room, capital and recurrent equipment and a
      dedicated nurse. Laryngeal swabs are suitable for older outpatients unable to
      produce adequate sputum. Each hospital should have a clinician trained in the
      diagnosis and management of childhood TB, including the interpretation of CXRs
      and skill in fine-needle aspiration. Radiologists and clinicians should use a
      simple, clear, internationally accepted classification of paediatric CXRs. The
      clinician(s) in charge of TB services should oversee all inpatients with TB and
      be at the forefront in running the TB clinic. A TB nurse specialist(s) should be
      part of the team. There is now a will to improve the diagnosis and management of
      childhood TB but bringing it to fruition requires efforts by the local TB
      service, paediatricians, radiology departments and laboratory services.

PMID- 18318945
TI  - Treatment of severe malnutrition with 2-day intramuscular ceftriaxone vs 5-day
      amoxicillin.
AB  - BACKGROUND: Systemic antibiotics are routinely prescribed for severe acute
      malnutrition (SAM). However, there is no consensus regarding the most suitable
      regimen. In a therapeutic feeding centre in Khartoum, Sudan, a randomised,
      unblinded, superiority-controlled trial was conducted, comparing once daily
      intramuscular injection with ceftriaxone for 2 days with oral amoxicillin twice
      daily for 5 days in children aged 6-59 months with SAM. METHODS: Commencing with
      the first measured weight gain (WG) following admission, the risk difference and
      95% confidence interval (95% CI) for children with a WG > or = 10 g/kg/day were
      calculated over a 14-day period. The recovery rate and case fatality ratio (CFR)
      between the two groups were also calculated. RESULTS: In an intention-to-treat
      analysis of 458 children, 53.5% (123/230) in the amoxicillin group and 55.7%
      (127/228, difference 2.2%, 95% CI -6.9-11.3) in the ceftriaxone group had a WG >
      or = 10 g/kg/day during a 14-day period. Recovery rate was 70% (161/230) in the
      amoxicillin group and 74.6% (170/228) in the ceftriaxone group (p=0.27). CFR was
      3.9% (9/230) and 3.1% (7/228), respectively (p=0.67). Most deaths occurred within
      the 1st 2 weeks of admission. CONCLUSION: In the absence of severe complications,
      either ceftriaxone or amoxicillin is appropriate for malnourished children.
      However, in ambulatory programmes, especially where there are large numbers of
      admissions, ceftriaxone should facilitate the work of medical personnel.

PMID- 18318946
TI  - Reduction of unnecessary transfusion and intravenous fluids in severely
      malnourished children is not enough to reduce mortality.
AB  - AIM: To test whether standardising the use of blood transfusions and intravenous
      (IV) infusions could reduce fatality in severely malnourished children admitted
      to Mulago Hospital, Kampala. METHODS: Improved adherence to the WHO protocol for
      blood transfusion and IV fluids was effected in patients with severe malnutrition
      by continuous medical education. A 'before and after' design was used to study
      450 severely malnourished children (weight-for-height < -3 Z-score or presence of
      oedema) under 60 months of age. A total of 220 pre- and 230 post-'improved
      practice' patients were enrolled consecutively during the periods September to
      November 2003 and September to December 2004, respectively. Patients were
      followed up until discharge or death. The Kaplan-Meier survival curve and the Cox
      regression hazard model were used for univariate and multivariate analyses,
      respectively. RESULTS: Overall case fatality was 23.6% (52/220) in the pre-period
      and 24.8% (57/230) in the post-period (p=0.78). Most of the deaths occurred in
      the 1st week of admission (73%, 38/52 in the pre-period and 61%, 35/57 in the
      post-period) and were of children who had received blood transfusion or IV
      infusion or both in the pre-period. Mortality in children transfused and/or
      infused was significantly reduced in the post-period (82%, 31/38 in the pre
      period vs 23%, 8/35 in the post-period, p=0.008). In the post-period, there was a
      significant reduction in the number of inappropriate blood transfusions (18%,
      34/194 vs 3.5%, 8/230, p=0.01) and IV fluid infusions (27%, 52/194 vs 9%, 20/230,
      p<0.001). Survival improved in children who received blood transfusions in the
      post-period [hazards ratio (HR) 0.22, 95% CI 0.30-1.67 vs HR 4.80, 95% CI 1.71
      13.51], as did that of children who received IV infusions (HR 2.10, 95% CI 0.84
      5.23 vs HR 3.91, 95% CI 1.10-14.04). CONCLUSION: Management according to the WHO
      protocol for severe malnutrition can reduce the need for blood and IV infusions.
      However, further studies are required to verify whether full implementation of
      the WHO protocol reduces the high case fatality in sub-Saharan hospitals.

PMID- 18318947
TI  - Clinico-epidemiological profile and predictors of severe illness in young infants
      (0-59 days) in Ghana.
AB  - BACKGROUND: Young infant mortality has remained high and relatively unchanged
      compared with deaths of older infants. Strategies to reduce infant mortality,
      however, are mostly targeted at the older child. OBJECTIVES: To describe the
      clinical profile of sick young infants presenting to a hospital and to define
      important signs and symptoms that will enable health workers to detect young
      infants with severe illness requiring hospital admission. METHODS: Young infants
      aged 0-59 days presenting to a paediatric out-patient clinic were evaluated by a
      nurse using a standardised list of signs and symptoms. A paediatrician
      independently evaluated these children and decided whether they needed
      hospitalisation. RESULTS: A total of 685 young infants were enrolled, 22% of whom
      were <7 days of age. The commonest reasons for seeking care were jaundice in the
      0-6-day group, skin problems in the 7-27-day group and cough in the 28-59-day
      group. The primary clinical diagnoses for admissions were sepsis in the 0-6- and
      7-27-day groups and pneumonia in the 28-59-day group. Clinical signs and symptoms
      predicting severe illness requiring admission were general (history of fever,
      difficult feeding, not feeding well and temperature >37.5 degrees C) and
      respiratory (respiratory rate > or =60/min, severe chest in-drawing). CONCLUSION:
      General and respiratory signs are important predictors for severe illness in
      young infants. Training peripheral health workers to recognise these signs and to
      refer to hospital for further assessment and management might have a significant
      impact on young infant mortality.

PMID- 18318948
TI  - Current usefulness of Crede's method of preventing neonatal ophthalmia.
AB  - The conjunctiva's bacterial profile at birth and 1 week after Crede's gonoccocal
      ophthalmic prophylaxis was evaluated over a 3-month period using culture and
      direct immunofluorescence. Thirty-four neonates received 10% silver vitellinate
      and 42 sterile saline. Chlamydia trachomatis was recovered in 7/34 and 9/42
      neonates receiving silver vitellinate and saline at birth and in 8/34 and 12/42
      after 1 week, respectively. Neisseria gonorrhoeae was not identified. Crede's may
      not be the ideal prophylactic method in areas with a low prevalence of N.
      gonorrhoeae.

PMID- 18318949
TI  - Management of primary congenital glaucoma by trabeculectomy in Nigeria.
AB  - AIM: To review the management of congenital glaucoma, bearing in mind the limited
      facilities available in developing countries. METHODS: The medical records of
      children aged < or = 3 years with primary congenital glaucoma seen at two
      teaching hospitals and one private eye hospital in Enugu, Nigeria over a 5-year
      period were reviewed retrospectively. All the children underwent trabeculectomy
      without use of anti-metabolites. RESULTS: Fifty-seven eyes of 32 patients (5
      unilateral, 26 bilateral) were reviewed. Pre-operatively, 63.2% of the eyes had a
      corneal diameter of 12-15 mm. After surgery, the number with corneal haziness
      decreased from 25 (43.8%) to 15 (26.4%) (p=0.05). The mean (SD) pre-operative
      intra-ocular pressure (IOP) was 28.3 (7.5) mmHg and the mean post-operative IOP
      was 17 (5.6) mmHg (p=0.001). CONCLUSIONS: When facilities for other treatment
      modalities are not available, primary trabeculectomy without the use of anti
      metabolites can be employed to manage primary congenital glaucoma.

PMID- 18318950
TI  - Typhoid intestinal perforation under 5 years of age.
AB  - BACKGROUND: Typhoid intestinal perforation is an important cause of morbidity and
      mortality in many developing countries. The peculiar features in children <5
      years old need to be recognised in order to improve outcome. OBJECTIVE: To
      determine the characteristic pattern and outcome of typhoid intestinal
      perforation in children under 5 years of age in south-east Nigeria. METHOD:
      Comparative analysis of 83 children with typhoid intestinal perforation between
      January 2001 and December 2006 at the University of Nigeria Teaching Hospital,
      Enugu. RESULTS: There were 22 (26.5%) children <5 years of age and 61 (73.5%) >5
      years. In the younger children, the predominant presentation was fever, vomiting
      and abdominal tenderness, and in the older children it was fever, abdominal pain
      and distension. Features of peritonitis were present in only 54.5% aged <5 years
      compared with 90.2% of the older children (p<0.001). The average number of
      perforations in the under-5s was 2.1 (range 1-4) and >1.3 (range 1-3) in the
      older children (p<0.01). The types of operative procedure (simple closure and
      segmental bowel resection) were similar in both groups. Post-operative
      complications were not significantly different in the two groups and included
      surgical wound infection, prolonged ileus, pulmonary infection, wound dehiscence,
      re-perforation, intra-abdominal abscess and incisional hernia. There were nine
      (40.9%) deaths in the <5s and 12 (19.7%) in the >5s (p<0.05). CONCLUSION: Typhoid
      intestinal perforation in children <5 is associated with atypical presentation
      and high mortality. A high index of suspicion will ensure earlier presentation
      and might improve outcome.

PMID- 18318951
TI  - Growth parameters in HIV-vertically-infected adolescents on antiretroviral
      therapy in Rio de Janeiro, Brazil.
AB  - BACKGROUND: Growth failure in HIV-infected children is an important factor in
      either initiating or changing antiretroviral therapy (ART). This study assesses
      the impact of HIV infection on growth parameters of adolescents who acquired HIV
      vertically. METHODS: This retrospective, longitudinal study involved adolescents
      aged 10-20 years with vertically-acquired HIV infection who were followed up in
      one of the three main referral centres for paediatric HIV/AIDS in Rio de Janeiro,
      Brazil. Length, weight and variables related to demographic, clinical and
      laboratory issues were analysed. RESULTS: 108 subjects were enrolled. Median age
      was 12.7 years, median duration of follow-up was 97.2 months and 61 (56.5%) were
      female. The difference between the baseline and final weight Z-scores was -0.31
      (p=0.02). Patients with final weight Z-scores < or = -2 used more ART regimens
      (average 4.13) than those with Z-scores > -2 (average 2.90, p<0.01) and also had
      a lower final CD4+ cell percentage--average 19% vs 24% (p<0.01), respectively.
      The difference between baseline and final-height Z-scores was -0.27 (p<0.01).
      Several factors were associated with a final-height Z-score < or = -2: clinical
      stage C during follow-up (RR 1.60, 95% CI 1.11-2.31), chronic diarrhoea during
      follow-up (RR 2.02, 95% CI 1.04-3.90), HAART use (RR 1.41, 95% CI 1.16-1.71),
      number of ART regimens (p<0.01) and final CD4+ cell percentage (p<0.01). In
      multivariate analysis, presentation in clinical stage C during follow-up was the
      only significant variable (OR 4.04, 95% CI 1.23-13.28). CONCLUSION: Even on
      HAART, HIV-infected adolescents have lower growth parameters than the normal
      population and this is associated with a worse prognosis.

PMID- 18318952
TI  - Fine needle aspiration biopsy: diagnostic utility in resource-limited settings.
AB  - BACKGROUND: Little information is available on the value of fine needle
      aspiration biopsy (FNAB) in routine paediatric practice in resource-limited
      settings. AIM: To provide an overview of all paediatric FNAB samples received at
      Tygerberg Hospital, Cape Town, South Africa over a 3-year period, including the
      determinants of sample adequacy and the diagnoses. METHODS: Samples were analysed
      from three locations: Tygerberg Hospital (TBH) where pathologists performed all
      the procedures, surrounding clinics where aspirates were mostly performed by
      doctors with no formal training in FNAB technique, and Queen Elizabeth Hospital,
      Blantyre, Malawi where FNABs were performed by trained nurse aspirators. RESULTS:
      A total of 830 aspirates were reviewed: 464 (56%) from TBH, 264 (32%) from local
      clinics and 102 (12%) from Blantyre. The main diagnoses at TBH were mycobacterial
      infection (31%), normal/reactive tissue (27%) and malignancy (14%); malignancy
      dominated (74%) in the select group from Blantyre. Sample adequacy rates were
      similar between pathologists and nurse aspirators [399/464 vs 82/102, odds ratio
      (OR) 1.4, 95% confidence interval (CI) 0.8-2.6]. Results were significantly
      better in the group who received formal training (TBH and Malawi) than in the
      clinics where clinicians had no formal training (481/566 vs 171/264, OR 3.1, 95%
      CI 2.2-4.4). CONCLUSIONS: FNAB provides a definitive tissue diagnosis in the
      majority of patients. Well-trained nurse aspirators perform as well as
      pathologists, indicating the feasibility of FNAB in resource-limited settings.

PMID- 18318953
TI  - Implementing an oxygen programme in hospitals in Papua New Guinea.
AB  - In Papua New Guinea (PNG), the most common cause of death among children under 5
      years of age is pneumonia. Children with severe pneumonia need antibiotics and
      oxygen but oxygen shortages are common owing to the cost and complex logistics of
      transporting it in cylinders. Detection of hypoxaemia using clinical signs can be
      difficult, especially in highly pigmented children in whom cyanosis is difficult
      to recognise. Pulse oximetry is the most reliable, non-invasive way of detecting
      hypoxaemia. However, most hospitals in PNG do not have pulse oximetry. We
      proposed that the installation of a reliable, sufficient and cheap supply of
      oxygen in hospitals coupled with the use of pulse oximetry would make a
      significant difference to child survival rates in PNG. Oxygen concentrators,
      which extract oxygen from ambient air, were installed in the children's wards of
      five hospitals during 2005. Pulse oximeters were also introduced to enable better
      detection of hypoxaemia. This paper describes the technical aspects of this
      programme: the equipment used and the rationale behind choosing it, the
      installation, commissioning and testing processes. The ongoing training of
      clinical and engineering staff as well as two follow-up evaluations are
      described.

PMID- 18318954
TI  - Brain abscesses in Malawian children: value of CT scan.
AB  - The clinical presentation and management of brain abscess in three HIV-uninfected
      Malawian children are reported. One case was associated with staphylococcal
      empyema and severe malarial anaemia and another case with chronic suppurative
      otitis media and mastoiditis. The third case had no identified extracranial focus
      of infection. These cases illustrate the difficulties of diagnosis and management
      of brain abscesses in the resource-poor setting where other causes of
      encephalopathy caused by infection are common, and highlight the value of
      neuroradiological imaging.

PMID- 18318955
TI  - Biodegradable hydrophobic-hydrophilic hybrid hydrogels: swelling behavior and
      controlled drug release.
AB  - The objective of this work was to investigate a new family of hydrophobic
      hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of
      hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo
      means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL
      Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of
      the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and
      0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine
      methiodide, was used as the model drug for the release study from the hybrid
      hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data
      of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors'
      feed ratio, and there were several-fold differences in swelling ratios between a
      pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of
      the hydrophobic PGCL-Ma component significantly reduced the initial burst
      swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios,
      the swelling data during the early period obeyed either Fickian diffusion (for
      50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and
      100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex
      Ma). A wide range of cocaine methiodide release profiles was achieved by
      controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug
      burst release was significantly reduced as the concentration of the hydrophobic
      PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine
      methiodide released during the 160-h period was via diffusion-controlled
      mechanism, while degradation-controlled mechanism dominated thereafter.

PMID- 18318956
TI  - Porous nano-hydroxyapatite/poly(vinyl alcohol) composite hydrogel as artificial
      cornea fringe: characterization and evaluation in vitro.
AB  - A nano-hydroxyapatite/poly(vinyl alcohol) (n-HA/PVA) composite hydrogel was
      employed as artificial cornea fringe to improve biocompatibility for the firm
      fixation between material and surrounding host tissues. The morphology and
      swelling behavior, as well as mechanical strength of the fringes were
      characterized. The results showed that the n-HA/PVA fringes had interconnective
      porous structure, high water content and good mechanical properties. With the aid
      of cell culture observed by inverted microscopy, scanning electron microscopy
      (SEM) and MTT test, it was concluded that PVA hydrogel modified with n-HA can
      improve biocompatibility and has no negative effects on the corneal fibroblasts
      in vitro. These findings indicate that the porous n-HA/PVA fringe can allow
      invasion and proliferation of cells, and can function as a fringe for artificial
      cornea.

PMID- 18318957
TI  - Optimal aggregation of dissociated islet cells for functional islet-like cluster.
AB  - Genetically-engineered islets can serve as a potential means to modulate the
      regional immunity occurring in the transplant environment, although gene transfer
      into islets is not easy due to the extracellular matrix of islets. In this study,
      we aggregated single islet cells dissociated by trypsinization for successful
      gene transfection into islet cells. To enhance the functionality of aggregated
      islets, we optimized the conditions for the aggregation of dissociated islet
      cells using several supplements such as collagen, all-trans-retinoic acid (atRA)
      and the culture medium of pancreatic exocrine cells (ECM). The dissociated islet
      cells formed tight cell clusters containing the normal insulin secretion against
      glucose concentration and the aggregation yield was significantly improved by
      treatment with atRA and ECM. However, collagen did not improve cell aggregation.
      Therefore, this re-aggregation technology would be useful for the development of
      genetically-engineered islets.

PMID- 18318958
TI  - In vitro and in vivo degradation behavior of acetylated chitosan porous beads.
AB  - Chitosans with different degree of acetylation (DA, 10-50%) were synthesized by
      the acetylation reaction of deacetylated chitosan and acetic anhydride with
      different ratios. The porous beads (approx. 500 mum) fabricated from the
      acetylated chitosans were used to investigate the degradation behaviors of
      chitosans with different DA in vitro and in vivo. The in vitro degradation
      behavior of the acetylated chitosan beads was investigated in solutions of
      lysozyme and/or N-acetyl-beta-D-glucosaminidase (NAGase), which are enzymes for
      chitosan present in the human body. It was observed that the degradation rate of
      acetylated chitosans can be controlled by adjusting the DA value: the degradation
      increased with increasing DA value of the acetylated chitosans. It seemed that
      NAGase plays an important role for the full degradation of chitosans in the body,
      even though NAGase itself can not initiate the degradation of chitosans. The in
      vitro degradation behavior of the chitosans in the mixture solution of lysozyme
      and NAGase was more similar to the in vivo degradation behavior than in the
      single lysozyme or NAGase solution. It may be owing to the sequential degradation
      reaction of chitosans in the mixture solution of lysozyme and NAGase (initial
      degradation by lysozyme to low-molecular-weight species or oligomers and the
      following degradation by NAGase to monomer forms). The in vivo degradation rate
      of acetylated chitosan beads was faster than the in vitro degradation rate. The
      acetylated chitosan porous beads with different DA value (and thus different
      degradation time) can be widely applicable as cell carriers for tissue
      engineering applications.

PMID- 18318959
TI  - Preparation of hydroxylated polyethylene surfaces.
AB  - The surfaces of high-density or ultra-high-molecular-weight polyethylenes were
      hydroxylated using a two-step process. The wetting and wear properties of the
      untreated (virgin) and surface hydroxylated polyethylenes were compared. The
      introduction of hydroxyl groups provided an increase in surface hydrophilicity
      resulting in reduced wear. Hydrophilicity was analyzed by optical analysis of
      water contact angle. Wear was determined by weight loss under conditions of a
      reciprocating pin-on-plate apparatus with the panels immersed in water or calf
      serum. These results suggest that hydroxylation of polyethylene friction-bearing
      orthopedic surfaces may lead to a longer joint life.

PMID- 18318960
TI  - Physical properties and biocompatibility of cellulose/soy protein isolate
      membranes coagulated from acetic aqueous solution.
AB  - A series of cellulose/soy protein isolate (SPI) membranes was prepared from
      cellulose and SPI solution by casting and coagulation from 5 wt% acetic acid and
      5 wt% sulphuric acid aqueous solution, respectively. The structure and properties
      of the membranes were characterized by Fourier transform infrared spectroscopy, X
      ray diffraction, scanning electron microscopy and tensile testing. The effects of
      SPI content (W(SPI)) and the coagulants on the structure and properties of the
      membranes were investigated. The membranes exhibited porous structure. The pore
      size in the surfaces and cross-sections of the membranes increased with an
      increase of W(SPI) regardless of the coagulants. The membranes containing 10 wt%
      W(SPI) showed higher tensile strength and elongation at break than other
      membranes. The membranes with the same W(SPI) coagulated from acetic acid
      solution exhibited higher values of tensile strength, elongation at break and
      pore size in the surfaces and cross-sections than those corresponding membranes
      coagulated from sulphuric acid. The biocompatibility of the acetic acid
      coagulated membranes was preliminarily evaluated by cell culture and in vivo
      implantation experiments. The results revealed that human umbilical vein
      endothelial cells (ECV304) grew well on this biomaterial. In comparison with the
      pure cellulose membrane, because of the incorporation of SPI and the resultant
      alteration of microstructure, the SPI-modified membranes showed an improved in
      vivo biocompatibility and biodegradability in the implantation experiments. These
      cellulose/SPI membranes warrant further explorations in biomedical fields.

PMID- 18318961
TI  - Improved blood compatibility of poly(ethylene terephthalate) films modified with
      L-arginine.
AB  - In order to improve the blood compatibility of the commonly used blood-contacting
      biomaterial poly(ethylene terephthalate) (PET), in this study PET films were
      chemically modified with L-arginine (L-Arg) by a three-step-procedure using
      glutaraldehyde (GA) as a cross-linker. The composition and chemical structure of
      PET and its change with surface modification were examined by X-ray photoelectron
      spectroscopy (XPS) and attenuated total reflection Fourier transform infrared
      (ATR-FT-IR) spectroscopy, while the change in hydrophilicity was judged by water
      contact angles measurement. The result of water contact measurement indicated
      that the modified films became more hydrophilic than PET with the contact angle
      decreasing from 78.5 degrees for PET to 43.7 degrees for PET-Arg. The protein
      adsorption on the film surface was evaluated by bicinchoninic acid assay (BCA)
      method, and the result showed that the L-Arg-modified films decreased the amount
      of protein adsorption by about 25%. The in vitro blood compatibility such as
      platelet adhesion (observed by scanning electron microscopy) and thrombus
      formation was also investigated, and the results demonstrated that the L-Arg
      modified films significantly suppressed platelet adhesion and aggregation and
      reduced the thrombus formation by about 67% compared with PET.

PMID- 18318962
TI  - Synthesis and characterization of phosphoryl-choline-capped poly(epsilon
      caprolactone)-poly(ethylene oxide) di-block co-polymers and its surface
      modification on polyurethanes.
AB  - By sequential ring-opening polymerization of ethylene oxide and epsilon
      caprolactone, poly(ethylene oxide) (PEO)-poly(epsilon-caprolactone) (PCL) di
      block co-polymers with a phosphoryl choline (PC)-terminated group were
      synthesized. Using FT-IR, NMR, DSC and SEC, the products were characterized and
      the results proved the successful synthesis of functionalized di-block co
      polymer. After blending the products with polyurethane (PU) and casting the
      result as film, the PEO segments migrated to the surface of the blend and the PCL
      segments acted as an anchor to fix the co-polymer on PU matrix, while the PEO
      segments provided PU the hydrophibility to prevent the fibrinogen adsorption on
      PU. This specific di-block co-polymer and the method of processing are hoped to
      be applied in the biomedical field to improve the biocompatibility of polymer
      materials.

PMID- 18318963
TI  - The influence of isocyanurate content on the bioperformance of hydrocarbon-based
      polyurethanes.
AB  - Bulk, surface and bioactivity of newly synthesized hydroxy telechelic
      polyisoprene-based (H-HTPI) polyurethane were investigated by means of ATR-FT-IR,
      contact-angle measurements, cell viability, calcification, and platelet and
      fibrinogen quantification. The influence of isophorone diisocyanates isocyanurate
      (I-IPDI) content on these properties was determined. Results generally showed a
      non-significant difference in these properties when they were compared with a
      commercially available biomedical polyurethane (PU), such as Tecoflex.
      Unexpectedly, where the increase of isocyanate content for commercial
      diisocyanate-based biocompatible PU significantly increases the surface contact
      angle, the new hydroxy telechelic polyisoprene-based PU showed a decrease of
      water contact angle with increasing I-IPDI content in the polymer. Nevertheless,
      the overall surface exhibited hydrophobic properties, i.e., theta > 85. Polymer
      cytotoxicity, assessed with L929 cell line in direct contact with the surface of
      the samples, showed no toxic effects on the cells. Interestingly, regardless of
      the I-IPDI content, platelet adhesion and fibrinogen adsorption, as well as the
      mineral deposition were fairly similar for all synthesized PUs. Our findings
      revealed that replacing diisocyanates by their isocyanurate homologues is a very
      relevant approach for preparation of polyurethanes with different mechanical
      properties while maintaining similar surface properties.

PMID- 18318965
TI  - Giving control to patients.

PMID- 18318966
TI  - Community-based maternity care in 2008.

PMID- 18318967
TI  - Heavy menstrual bleeding: delivering patient-centred care.

PMID- 18318968
TI  - Delay between pregnancy confirmation and sickle cell and [corrected] thalassaemia
      screening: a population-based cohort study.
AB  - BACKGROUND: Antenatal sickle cell and thalassaemia screening sometimes occurs too
      late to allow couples a choice regarding termination of affected fetuses. The
      target gestational age for offering the test in the UK is 10 weeks. AIM: To
      describe the proportion of women screened before 70 days' (10 weeks') gestation
      and the delay between pregnancy confirmation in primary care and antenatal sickle
      cell and thalassaemia screening. DESIGN OF STUDY: Cohort study of reported
      pregnancies. SETTING: Twenty-five general practices in two UK inner-city primary
      care trusts offering universal screening. METHOD: Anonymised data on all
      pregnancies reported to participating general practices was collected for a
      minimum of 6 months. RESULTS: There were 1441 eligible women intending to proceed
      with their pregnancies, whose carrier status was not known. The median
      (interquartile range [IQR]) gestational age at pregnancy confirmation was 7.6
      weeks (6.0-10.7 weeks) and 74% presented before 10 weeks. The median gestational
      age at screening was 15.3 weeks (IQR = 12.6-18.0 weeks), with only 4.4% being
      screened before 10 weeks. The median delay between pregnancy confirmation and
      screening was 6.9 weeks (4.7-9.3 weeks) After allowing for practice level
      variation, there was no association between delay times and maternal age, parity,
      and ethnic group. CONCLUSION: About 74% of women consulted for pregnancy before
      10 weeks' gestation but fewer than 5% of women were screened before the target
      time of 10 weeks. Reducing the considerable delay between pregnancy confirmation
      in primary care and antenatal sickle cell and thalassaemia screening requires
      methods of organising and delivering antenatal care that facilitate earlier
      screening to be developed and evaluated.

PMID- 18318970
TI  - Parents' experiences of universal screening for haemoglobin disorders:
      implications for practice in a new genetics era.
AB  - BACKGROUND: England is the only country in the world that currently has universal
      population screening for haemoglobin disorders through linked antenatal and
      newborn screening. Little is known about the acceptability of such screening.
      AIM: To explore parents' experiences of, and attitudes towards, new universal
      genetic screening for haemoglobin disorders. DESIGN OF STUDY: Narrative interview
      study. SETTING: Primary and community care settings across England. METHOD:
      Narrative interviews were undertaken with a maximum variation sample of 39 people
      who had experienced gene-carrier identification through antenatal and newborn
      screening for sickle cell, thalassaemia, and other haemoglobin variants within
      the previous 2 years. RESULTS: Most parents were unaware screening had occurred
      or had given it little consideration and so were surprised or shocked by results.
      However, they were glad to learn of their carrier status, reproductive genetic
      risk, or their newborn's carrier status. Participants emphasised that antenatal
      screening should happen as early as possible. Many would rather have known their
      carrier status before pregnancy or before entering a relationship. Although most
      were satisfied with the information they received, significant misunderstandings
      remained. There were culturally diverse attitudes towards prenatal diagnosis and
      termination. These procedures were acceptable to some parents with strong
      religious beliefs, including Christians and Muslims. CONCLUSION: Parents support
      screening for haemoglobin disorders but need to be better informed and better
      prepared for results and what they mean. Sensitivity to patient diversity in
      attitudes and choices is also required. Universal screening for genetic
      reproductive risk will increasingly involve generalists, particularly in primary
      care, presenting opportunities for screening before or earlier in pregnancy,
      which is likely to be welcomed by patients.

PMID- 18318971
TI  - Becoming pregnant: exploring the perspectives of women living with diabetes.
AB  - BACKGROUND: The risk of adverse pregnancy outcome for women with type 1 diabetes
      is reduced through tight diabetes control. Most women enter pregnancy with
      inadequate blood glucose control. Interview studies with women suggest the
      concept of 'planned' and 'unplanned' pregnancies is unhelpful. AIM: To explore
      women's accounts of their journeys to becoming pregnant while living with type 1
      diabetes. DESIGN OF STUDY: Semi-structured interviews with 15 women living with
      pre-gestational type 1 diabetes, between 20 and 30 weeks gestation and with a
      normal pregnancy ultrasound scan. SETTING: Four UK specialist diabetes antenatal
      clinics. METHOD: Interviews explored women's journeys to becoming pregnant and
      the impact of health care. Analysis involved comparison of women's accounts of
      each pregnancy and a thematic analysis. RESULTS: Women's experiences of becoming
      pregnant were diverse. Of the 40 pregnancies described, at least one positive
      step towards becoming pregnant was taken by 11 women in 23 pregnancies but not in
      the remaining 17 pregnancies, with variation between pregnancies. Prior to and in
      early pregnancy, some women described themselves as experts in their diabetes but
      most described seeking and/or receiving advice from their usual health
      professionals. Three women described pre-conception counselling and the anxiety
      this provoked. CONCLUSION: For women living with type 1 diabetes each pregnancy
      is different. The concept of planned and unplanned pregnancy is unhelpful for
      designing health care. Formal preconception counselling can have unintended
      consequences. Those providing usual care to women are well positioned to provide
      advice and support to women about becoming pregnant, tailoring it to the changing
      needs and situation of each woman.

PMID- 18318973
TI  - Identifying undiagnosed diabetes: cross-sectional survey of 3.6 million patients'
      electronic records.
AB  - BACKGROUND: Around 1% of the UK population has diabetes that is either
      undiagnosed or unrecorded on practice disease registers. AIM: To estimate the
      number of people in UK primary care databases with biochemical evidence of
      undiagnosed diabetes. To develop simple practice-based search techniques to
      support early recognition of diabetes. DESIGN OF STUDY: Cross-sectional survey of
      3 630 296 electronic records. SETTING: Four hundred and eighty UK practices
      contributing to the QRESEARCH database. METHOD: Electronic searches to identify
      people with no diabetes diagnosis in one of two categories (A and B), using the
      most recently recorded blood glucose measurement: random blood glucose level
      >or=11.1 mmol/l or fasting blood glucose level >or=7.0 mmol/l (A); either a
      random or a fasting blood glucose level >or=7.0 mmol/l (B). An additional outcome
      measure was the proportion of the population with at least one blood glucose
      measurement in the record. RESULTS: The number (percentage) identified in
      category A was 3758 (0.10% of the total population); the number in category B was
      32 785 (0.90%). Projected to a practice of 7000 patients, around eight patients
      have biochemical evidence of undiagnosed diabetes, and 68 have results suggesting
      the need for further follow-up. One-third of people aged over 40 years without
      diabetes have a blood glucose measurement in the past 2 years in their record.
      CONCLUSION: People with possible undiagnosed diabetes are readily identifiable in
      UK primary care databases through electronic searches using blood glucose data.
      People with borderline levels, who may benefit from interventions to reduce their
      risk of progression to diabetes, can also be identified using practice-based
      software.

PMID- 18318974
TI  - Predicting who will benefit from an Expert Patients Programme self-management
      course.
AB  - BACKGROUND: In England, the Expert Patients Programme, a lay-led chronic disease
      self-management course, was developed to improve self-care support and skills.
      The course is designed for anyone with a self-defined long-term condition, and
      attracts a heterogeneous group of patients. A randomised controlled trial has
      demonstrated effectiveness in improving subjective health. However, it is not
      known whether particular patient characteristics predict the impact of the
      course. AIM: To determine whether baseline characteristics predict clinical
      outcomes from attendance at a chronic disease self-management course; and to
      assess whether identification of such characteristics assists in targeting the
      course to individuals most likely to benefit. DESIGN OF STUDY: A post-hoc
      subgroup analysis of data from a randomised controlled trial to explore
      predictors of three trial outcomes: self-efficacy, energy, and health-related
      quality of life. SETTING: Participants with self-defined long-term conditions (n
      = 629) were recruited from community settings in all 28 strategic health
      authorities in England. METHOD: Multiple regression was used to examine
      interactions between baseline variables and trial outcomes. RESULTS: The
      predictors demonstrating significant interactions were: age and general health,
      and baseline values for self-efficacy, energy levels, and health-related quality
      of life. CONCLUSION: Participants with lower self-efficacy and health-related
      quality of life at baseline demonstrated more positive health outcomes. The
      Expert Patients Programme may have a protective effect on health-related quality
      of life for patients with poor health and low confidence. Younger people
      benefited substantially more than older people. Results suggest that positive
      outcomes associated with the course will be demonstrated with a wide variety of
      patients, although it may be worthwhile encouraging attendance of younger
      patients, those lacking confidence, and those coping poorly with their condition.

PMID- 18318975
TI  - Connecting for health.

PMID- 18318976
TI  - Salaried GPs.

PMID- 18318977
TI  - GPs' working lives.

PMID- 18318978
TI  - On strengthening primary care.

PMID- 18318980
TI  - Appraisals.

PMID- 18318981
TI  - Adolescent anger or angst?

PMID- 18318982
TI  - Complementary and alternative medicine: what the NHS should be funding?

PMID- 18318983
TI  - What Sir Luke Fildes' 1887 painting The Doctor can teach us about the practice of
      medicine today.

PMID- 18318989
TI  - The functional roles of lipid rafts in T cell activation, immune diseases and HIV
      infection and prevention.
AB  - The first appearance of lipid rafts, or lipid rafts-like structure, was
      occasionally observed by cryo-electronic microscopy in 1980s as cavity, such as
      caveolae. However, the fully understanding of lipid raft was attributed by the
      studies of T cell activation, virus entry/budding, and other membrane events.
      During the interaction of T cell and antigen presenting cell, a highly organized
      structure is formed at the interface of the two cells, where cholesterol and
      sphingolipids are enriched, and form a liquid ordered phase that facilitates the
      signaling proteins on and off. Lipid rafts are also involved in virus entry and
      assembly. In this review, we will discuss cholesterol-sphingolipid floating
      microdomain, the lipid raft as a unique compartment of the plasma membrane, with
      biological functions that ensure correct intracellular traffic of proteins and
      lipids, such as protein-protein interactions by concentrating certain proteins in
      these microdomains, while excluding others. We also discuss the disruption of
      lipid rafts is related to different diseases and aging, and we especially exploit
      the lipid rafts as pharmaceutical targets for anti-virus and anti-inflammation,
      particularly a new approach to control HIV infection for AIDS prevention and
      protection by inhibition or disruption of lipid rafts.

PMID- 18318990
TI  - The classical and regulatory functions of C1q in immunity and autoimmunity.
AB  - A classical function of C1q is to bind immune complexes and initiate complement
      activation producing membrane lytic complexes, opsonins and anaphylatoxins. This
      classical pathway of complement activation is also elicited when C1q binds some
      other ligands. Besides complement activation, C1q also regulates cell
      differentiation, adhesion, migration, activation and survival. C1q deficiency is
      associated with autoimmunity as well as increased susceptibility to infections.
      In this article, we discuss the basic properties of C1q, its expression, and
      classical and regulatory functions.

PMID- 18318991
TI  - The immunopharmaceutical effects and mechanisms of herb medicine.
AB  - In recent years, studies on evaluation of the therapeutic and toxic activity of
      herbal medicinal products became available and popular. The advances in modern
      biotechnology have led to discovery of many new active constituents. However, it
      is a constant challenge to establish the pharmacological basis for efficacy and
      safety of herbal medicinal products. A better understanding of the effects and
      bioavailability of phytopharmaceuticals can help in discovering suitable and
      rational therapies. In this review, we present the bioavailability studies in
      immune system that has been conducted for some of the more important or widely
      used phytopharmaceuticals. Furthermore, various new drug targets worthy of using
      for drug development in immunomodulating herbal medicine area and their
      regulatory mechanisms are also discussed. Adverse effects, drug interactions, and
      contraindications are also discussed which show that caution should be exercised
      when combining phytopharmaceuticals with chemically derived pharmaceutical
      components.

PMID- 18318992
TI  - Fine-tuned expression of programmed death 1 ligands in mature dendritic cells
      stimulated by CD40 ligand is critical for the induction of an efficient tumor
      specific immune response.
AB  - During maturation, murine myeloid dendritic cells (DCs) upregulated the
      expressions of CD11c, CD25, CD40, CD80, CD86, MHC II and programmed death 1
      ligands 1 and 2 (PD-L1 and PD-L2). Differential expression patterns of PD-L1 and
      PD-L2 were found when DCs were triggered by CD40 ligand and TNF-alpha. PD-L1
      expression was repressed and PD-L2 expression remained unchanged in mature CD40
      ligated DCs, whereas TNF-alpha stimulated DCs kept high expression of PD-L1 and
      significantly enhanced PD-L2 expression on DCs. Proliferations of T lymphocytes
      stimulated by immature DCs were enhanced by blockade of the PD-1 and PD-1 ligand
      interaction. But inhibitive effects were found in T lymphocytes stimulated by
      CD40-ligated DCs. With the fine-tuned expressions of PD-L1 and PD-L2, CD40
      ligated DCs could sustain a longer activation period and elicit a more efficient
      T lymphocyte activation.

PMID- 18318993
TI  - IL-10 gene modified dendritic cells inhibit T helper type 1-mediated alloimmune
      responses and promote immunological tolerance in diabetes.
AB  - Dendritic cells (DCs) have the potency to regulate the outcome of autoimmunity
      through the modulation of immune responses. The induction of antigen specific
      tolerance is critical for prevention and treatment of allograft rejection. In the
      present study, we transfected IL-10 gene into DCs and investigated their effect
      on inhibition of lymphocyte activity in vitro and induction of immune tolerance
      on islet allograft in mice. An IDDM C57BL/6 mouse model was induced by
      streptozotocin. The islet cells isolated from the BALB/c mice were transplanted
      into the kidney capules of the model mice followed by injection of IL-10 modified
      DCs (mDCs). The results showed that mDCs could significantly inhibit T lymphocyte
      proliferation mediated by allotype cells and induce its apoptosis, whereas,
      unmodified DCs (umDCs) could promote the murine lymphocyte proliferation
      markedly. The injection of mDCs could prolong the survival of allotype islet
      transplanted IDDM mice. The average plasma glucose (PG) level in mDCs treated
      mice returned to normal within 3 days and lasted for about 2 weeks. The rejection
      response in control mice occurred for 5 days after transplantation. The level of
      IFN-gamma was lower while IL-4 was higher in mDCs treated mice than that in umDCs
      treated mice, which indicated that Th1/Th2 deviation occurred. Our studies
      suggest that IL-10 gene modified DCs can induce the immune tolerance to islet
      graft and prolong survival of the recipients by the inhibiting of T cell
      proliferation in allotype mice.

PMID- 18318994
TI  - Establishment and characterization of a cell based artificial antigen-presenting
      cell for expansion and activation of CD8+ T cells ex vivo.
AB  - Artificial antigen-presenting cells are expected to stimulate the expansion and
      acquisition of optimal therapeutic features of T cells before infusion. Here CD32
      that binds to a crystallizable fragment of IgG monoclonal antibody was
      genetically expressed on human K562 leukemia cells to provide a ligand for T-cell
      receptor. CD86 and 4-1BBL, which are ligands of co-stimulating receptors of CD28
      and 4-1BB, respectively, were also expressed on K562 cells. Then we accomplished
      the artificial antigen-presenting cells by coupling K32/CD86/4-1BBL cell with
      OKT3 monoclonal antibody against CD3, named K32/CD86/4-1BBL/OKT3 cells. These
      artificial modified cells had the abilities of inducing CD8+ T cell activation,
      promoting CD8+ T cell proliferation, division, and long-term growth, inhibiting
      CD8+ T cell apoptosis, and enhancing CD8+ T cell secretion of IFN-gamma and
      perforin. Furthermore, antigen-specific cytotoxic T lymphocytes could be retained
      in the culture stimulated with K32/CD86/4-1BBL/OKT3 cells at least within 28
      days. This approach was robust, simple, reproducible and economical for expansion
      and activation of CD8+ T cells and may have important therapeutic implications
      for adoptive immunotherapy.

PMID- 18318995
TI  - Characterization of a novel anti-DR5 monoclonal antibody WD1 with the potential
      to induce tumor cell apoptosis.
AB  - TNF-related apoptosis-inducing ligand (TRAIL) is a TNF family member capable of
      inducing apoptosis. Death receptor 5 (DR 5) is a key receptor of TRAIL and plays
      an important role in TRAIL-induced apoptosis. To prepare monoclonal antibodies
      (mAbs) against DR5, cDNA encoding soluble DR5 (sDR5) was firstly amplified by
      reverse transcriptase-polymerase chain reaction (RT-PCR) with specific primers,
      and then inserted into a prokaryotic expression vector pET-30a. The recombinant
      plasmid was expressed in Escherichia coli strain BL21 (DE3), and sDR5 was
      purified by nickel affinity chromatography. As an antigen, sDR5 was used to
      immunize mice. Hybridomas secreting antibodies against sDR5 were identified. One
      positive clone was selected to produce antibody, WD1. ELISA and
      immunofluorescence demonstrated that WD1 could bind recombinant sDR5 and membrane
      bound DR5 (mDR5) on Jurkat and Molt-4 cells. ATPLite assays showed that Jurkat
      and Molt-4 cells were sensitive to the antibody in a dose dependent manner. The
      Annexin V/PI assays and Giemsa's staining both showed that WD1 could induce
      Jurkat cell apoptosis efficiently. Transient transfection of 293T cells and
      indirect immunofluorescence assay demonstrated that mAb (WD1) couldn't cross
      react with DR4. Our findings indicated that the novel antibody, WD1 could act as
      a direct agonist, bind DR5 characteristically, and initiate efficient apoptotic
      signaling and tumor regression. Thus, WD1 would be a leading candidate for
      potential cancer therapeutics.

PMID- 18318996
TI  - RGD-FasL induces apoptosis of pituitary adenoma cells.
AB  - This study was to investigate the cytotoxic effects on pituitary adenoma cell
      lines GH3/MMQ/AtT20 induced by RGD-FasL and the underlying mechanism. Fas/DcR3
      mRNAs were detected by RT-PCR and their surface expressions were measured by flow
      cytometry. Cytotoxicity exerted by RGD-FasL on tumor cells was measured with MTT
      assay and the induced apoptosis was determined by agarose gel electrophoresis.
      The cell cycle and apoptosis was assessed by flow cytometry with PI staining. The
      expressions of caspase8/9/3, Bcl-2, RANKL and JNK2 were detected by Western
      blotting. Approximately 13.7% of GH3 cells, 25.5% of MMQ cells, 22.2% of AtT20
      cells express Fas, while 23.9% of GH3 cells, 24.1% of MMQ cells, 4.6% of AtT20
      cells express DcR3. The cytotoxic effects of FasL/RGD-FasL on tumor cells were
      all taken in a dose-dependent manner. Cell lines MMQ/AtT20 showed the same
      sensitivity to RGD-FasL as to FasL, while cell line GH3 was less sensitive to RGD
      FasL. The cell cycle analysis indicated that RGD-FasL could inhibit cells in
      G0/G1 phase and G2/M phase. In MMQ and AtT20 cells treated with RGD-FasL, the AI
      was not significantly different from that treated with FasL, while in GH3 cells
      treated with RGD-FasL, the AI was lower than that treated with FasL. The
      expressions of caspase-8/9/3, RANKL and JNK2 were increased while that of Bcl-2
      was decreased after treatment with RGD-FasL, suggesting that RGD-FasL induces
      apoptosis through caspase activation. We concluded that RGD-FasL could possibly
      be considered as a novel therapeutical candidate for the treatment of pituitary
      adenomas.

PMID- 18318997
TI  - The expression of CD2 in chronic HBV infection.
AB  - It was previously reported that several kinds of intercellular adhesion molecules
      are closely related to chronic HBV infection. The complex of CD2 and CD58 plays
      an important role in enhancing the adhesion of T lymphocytes to target cells, and
      promoting hyperplasia and activation of T lymphocytes. In this study, we detected
      the level of CD2 expressed on the surface of PBMC, the expression level of CD2
      mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with
      chronic HBV infection and compared them with the expression level of normal
      controls. We also determined the level of serum HBV DNA from patients with
      chronic HBV infection and from normal controls. The clinical characteristics of
      hepatic function were tested as well. The results showed that the expression of
      CD2 significantly increased with the severity of chronic HBV infection, which
      suggested that CD2 might contribute to the hepatocyte damage in chronic HBV
      infection.

PMID- 18318998
TI  - Analysis of 15 years of skin cancer in central Iran (Yazd).
AB  - Skin cancer incidences over a 15-year period (1987-2001) were studied in Yazd, a
      hot, dry, desert area in the center of Iran. The mean skin cancer frequency was
      determined to be 28.6 percent and 1,124 patients were diagnosed with skin cancer
      during this time period, approximately 11 per 100,000. The most common skin
      cancer was basal cell carcinoma, accounting for 76.9 percent. Squamous cell
      carcinoma was diagnosed in 18.1 percent and melanoma in 2.7 percent; 2.3 percent
      were other uncommon skin cancers. Most cancers were diagnosed in the seventh and
      eighth decades of life. The face, head, and neck were the sites of 92 percent of
      skin cancers. The sex ratio was determined to be 1.6 (male/female), similar to
      other reported populations. However, melanoma was found to be 1.5 times higher in
      men in this study, in contrast to most studied populations. Skin cancer incidence
      in Iran is lower than western countries. It is very likely that clothing and body
      covering customs can account for such differences.

PMID- 18318999
TI  - Cryotherapy for anogenital warts: factors affecting therapeutic response.
AB  - Human papilloma virus genital infection remains a treatment dilemma; there is
      still no gold standard therapy, treatment options are limited, expensive and
      often ineffective, and recurrence rates are relatively high. The primary
      objective of this study is to establish the efficacy, safety, and tolerability of
      cryotherapy in the treatment of these lesions. From 1999 to 2003, 100 consecutive
      patients with at least ten genital warts were treated with liquid nitrogen
      cryotherapy using a cotton-tipped applicator and two freeze-thaw cycles at the
      outpatient dermatology clinic of Hazrat-e Rasool University Hospital. Treatment
      was repeated every 3 weeks until the disappearance of all visible lesions was
      achieved. Patients were followed up every 4 months for 18 months. Complete
      clinical cure (CCC) was defined as complete clearance of all lesions and no
      evidence of disease for a minimum of 18 months. The CCC and relapse rate were
      evaluated based on different demographic and clinical characteristics. Overall,
      86 percent of the patients achieved CCC after an average of 3.31 treatment
      sessions. All of the failed cases were attributed to recurrence of warts in new
      sites. The cure rate increased in parallel with increasing treatment sessions
      until the 6th session, after which it remained constant. The cure rate was lower
      and the number of treatment sessions higher in older patients. The age of the
      patient and number of treatment sessions affect the cure rate. The recurrence
      rate was significantly higher for the married or multi-partner group than for
      unmarried patients. We concluded that cryotherapy is an effective method for
      treatment of anogenital warts. The age of the patient and size of the lesions
      affect the cure rate. However, the most important factor in relapse of the
      lesions is unprotected sexual contact during and after treatment.

PMID- 18319000
TI  - StopPicking.com: Internet-based treatment for self-injurious skin picking.
AB  - StopPicking.com is an interactive self-help approach derived from an evidence
      based cognitive behavioral model of treatment for skin picking (SP). We examined
      the development and two phases of program evaluation for an Internet-based self
      help treatment for self-injurious SP. Participants included 372 individuals
      consecutively enrolling in StopPicking.com during a 5-month period. Results
      revealed significant reductions in frequency of picking episodes and symptom
      severity ratings from baseline to post-intervention. Treatment response rates
      were comparable or superior to previous research utilizing pharmacotherapy for
      the treatment of SP suggesting that StopPicking.com may provide an alternative or
      adjunctive treatment for SP. The current study is limited by lack of a control
      condition and use of a non-referred sample of skin pickers.

PMID- 18319001
TI  - Azithromycin: a new therapeutical strategy for acne in adolescents.
AB  - AIM: To study the efficacy, safety, and compliance of 500 mg azithromycin thrice
      weekly for 8 weeks to treat acne vulgaris in adolescents. METHODS: An open-label,
      non-comparative study was carried out for 8 weeks. Fifty-two teenagers with
      moderate to severe papulo-pustular acne vulgaris were enrolled. Azithromycin, 500
      mg orally thrice weekly for 8 weeks, was prescribed. No topical treatment was
      permitted. At the baseline visit, patients were scheduled to return at two-weekly
      intervals for 8 weeks. Efficacy was gauged by the percentage clearance of papulo
      pustular acne lesions. All patients were also evaluated at four months post
      treatment. RESULTS: A majority of patients (47/52) showed remarkable improvement
      in the first 4 weeks with a more than 20 percent reduction of their inflammatory
      papulo-pustular lesions. Maximum clearance was observed in 32 patients at 8
      weeks. Slow improvement with eruptions of new lesions was seen in 6 patients.
      Adverse events, such as heartburn and nausea, were reported by 3 patients. All
      patients completed the 8-week study period. The beneficial effect was maintained
      at 4 months after the conclusion of treatment. CONCLUSIONS: Azithromycin, 500 mg
      thrice weekly for 8 weeks, appears to be a safe and effective treatment for acne
      vulgaris in adolescents, with excellent patient compliance.

PMID- 18319002
TI  - Drug representatives: giving you lunch or stealing your soul?
AB  - Pharmaceutical companies and their representatives attempt to influence the
      practice of medicine by giving gifts. Gifts, even those of trivial monetary
      value, impart a sense of obligation that conflicts with the provider's primary
      responsibility to the patient. Providers are less likely than their patients and
      peers to believe that gifts change their own prescribing habits, making them
      vulnerable to manipulation by industry. Providers who interact with drug reps
      must exercise caution to prevent compromise of the patient-physician
      relationship.

PMID- 18319003
TI  - Complete response in a cutaneous facial metastatic nodule from renal cell
      carcinoma after hypofractionated radiotherapy.
AB  - Cutaneous metastases from renal cell carcinoma (RCC) are uncommon, but may be
      painful and deforming. A review of the English language literature yields no
      references regarding the use of radiotherapy in the palliation of cutaneous RCC
      metastases. We report the first documented case of a patient with a single RCC
      facial metastatic nodule treated with hypofractionated electron beam radiotherapy
      followed by administration of sorafenib. The patient achieved a complete
      resolution of the cutaneous metastasis.

PMID- 18319004
TI  - Posttransplant Epstein-Barr virus related lymphoproliferative disorder with a
      primary cutaneous presentation.
AB  - Posttransplant lymphoproliferative disorder is a rare and often difficult
      diagnosis in patients with only cutaneous symptoms. A stepwise approach to
      diagnosis and classification can lead to successful treatment. We report a case
      of an EBV-associated posttransplant lymphoproliferative disorder (PTLD) occurring
      on the face with a primary cutaneous presentation. The appropriate diagnosis was
      made only after multiple biopsies and special stains. There was near complete
      resolution with decreased levels of iatrogenic immunosuppression. The diagnosis
      of Posttransplant lymphoproliferative disorder can be difficult to establish. A
      proper workup will aid in making an accelerated diagnosis and choosing
      appropriate treatment options.

PMID- 18319005
TI  - Imipramine-induced hyperpigmentation of the skin.

PMID- 18319006
TI  - Granulomatous rosacea-like demodicidosis.
AB  - Demodicidosis may present as pityriasis folliculitis, papulopustular lesions,
      rosacea-like eruptions, and granulomatous rosacea-like eruptions. We report a
      case of demodex granuloma presenting with recurrent granulomatous rosacea-like
      papules on the face in a middle-aged woman. The diagnosis of demodicidosis was
      made by finding extrafollicular mites in the perifollicular inflammatory
      infiltrate. The papules resolved after 3 weeks of systemic and topical
      metronidazole, and low-dose oral prednisolone therapy. In summary, demodex
      granuloma may be mistaken for granulomatous rosacea-like papules. Correct
      diagnosis can be facilitated by finding extrafollicular demodex mites in skin
      biopsy specimens.

PMID- 18319007
TI  - Acquired lymphangioma circumscriptum of the vulva.
AB  - Lymphangiomas are rare benign proliferations of the lymphatic system. Acquired
      lymphangioma circumscriptum of the vulva is induced by impaired lymph flow. We
      describe a new case of lymphangioma circumscriptum resulting from tuberculosis
      involving a lymph node. A 45-year-old female presented with swelling of the vulva
      for the past 8 years. She had a history of multiple left inguinal swellings
      successfully treated with four antituberculosis drugs. Her vulval swelling did
      not respond and was diagnosed as acquired lymphangioma circumscriptum. She
      becomes the fifth reported case of acquired lymphangioma circumscriptum of the
      vulva with tubercular lymphadenitis. The single antituberculosis treatment is
      insufficient to control lymphangioma. Ablative methods seem encouraging.

PMID- 18319008
TI  - KID syndrome.
AB  - KID syndrome is a rare congenital disorder characterized by keratitis,
      ichthyosis, and deafness. We have described a 4-year-old girl who is treated with
      bland emollients and topical keratolytics such as urea and surprisingly observed
      marked improvement in skin hyperkeratosis and palmoplantar keratoderma. We think
      that along with urgent ophthalmologic and otolaryngologic measures, simple
      topical therapies may improve skin condition in KID syndrome precluding the
      possible hazards of systemic retinoid therapy.

PMID- 18319009
TI  - Numerous fibrous papules of the face unassociated with any genodermatosis.
AB  - Numerous angiofibromas on the face are commonly associated with tuberous
      sclerosis or multiple endocrine neoplasia type 1. We present a healthy 66-year
      old female with numerous facial angiofibromas, without evidence of tuberous
      sclerosis, multiple endocrine neoplasia type 1, or any of the less common
      syndromes associated with many angiofibromas on the face. To our knowledge, there
      have been no previously reported cases of patients with numerous facial
      angiofibromas who did not have an associated genodermatosis.

PMID- 18319010
TI  - Capecitabine induced inflammation of actinic keratoses.
AB  - Capecitabine, an oral prodrug of 5-fluorouracil, is a systemic chemotherapeutic
      agent used in the treatment of metastatic breast and colon cancer. Patients
      undergoing capecitabine therapy may experience inflammation and irritation of
      existing actinic keratoses. Oncologists and dermatologists alike should be aware
      of this side effect.

PMID- 18319011
TI  - Protracted superficial Wegener granulomatosis in a child.
AB  - Wegener granulomatosis is a rare, chronic, multisystemic vasculitis affecting
      mainly the upper and lower respiratory tracts together with glomerulonephritis,
      but the disease may involve any other organ. Protracted superficial form is a
      rare variant of the disease. We report a case of protracted superficial Wegener
      granulomatosis in a 16-year-old boy in whom the disease started with recurrent
      digital ulcers at age 7 years. Later, he developed nodules and papules associated
      with upper airway involvement and ocular keratitis without lung or renal
      involvement. C-ANCA was positive. The patient was treated with oral prednisone.
      Similar cutaneous and mucosal lesions developed during two relapses of the
      disease without renal or respiratory involvement.

PMID- 18319012
TI  - Linear porokeratosis.
AB  - Linear porokeratosis is a rare variant. It can be present at birth or can develop
      in adult life. Lesions of linear porokeratosis are grouped and linearly arranged
      along the lines of Blaschko. On the extremities it affects the distal portion
      more than the proximal areas. On the trunk these can be zosteriform in
      distribution. Lesions of linear porokeratosis probably result from an abnormal
      clone of epidermal precursors. A 20 year old male presented with annular plaques
      in linear pattern following the lines of Blaschko over the left upper limb
      extending up to the axilla present since childhood. The lesions had atrophic
      centre and raised hyperkeratotic borders. The lesions were more proximal than
      distal. Few scattered lesions were present on left side of trunk. There was no
      family history of such lesions. Systemic examination of patient was normal. On
      histopathological examination there was hyperkeratosis and parakeratosis. A
      coronoid lamella was present. At the base of coronoid lamella thinned out
      granular layer and necrotic keratinocytes were also seen. In the dermis pigment
      incontinence and perivascular lymphocytic infiltrate were present. This case is
      being reported because of its rarity. It is an atypical presentation because the
      lesions were disposed more over proximal than distal area of upper limb. Linear
      porokeratosis is associated with an increased risk of malignant transformation.

PMID- 18319013
TI  - Osteo-nevus of Nanta (osseous metaplasia in a benign intradermal melanocytic
      nevus): an uncommon phenomenon.

PMID- 18319014
TI  - A clinically practical way to estimate surgical blood loss.

PMID- 18319015
TI  - Improvement of patient tolerance to dapsone: current and future developments.

PMID- 18319016
TI  - Isolated sixth nerve palsy following low dose oral methotrexate.

PMID- 18319017
TI  - Looking beyond the borders of our specialty: the 2006 Clarence S. Livingood MD
      Lecture.
AB  - The following is adapted from the Clarence S. Livingood Lecture delivered at the
      2006 American Academy of Dermatology Annual Meeting. The Livingood Lecture is the
      only presentation during the Annual Meeting of the American Academy of
      Dermatology that is specifically dedicated to issues other than the science and
      practice of dermatology. The lecture describes the impact of the
      compartmentalization of Medicine. Compartments prevent us from seeing certain
      things and make some of our own observations untrustworthy. Furthermore,
      compartments affect the context in which we interpret our observations. These
      limitations on perception impact the physician-patient relationship and outcomes
      of care, as well as inter-specialty relationships. Compartments may even play a
      critical role in world conflicts. We would be wise to follow Dr. Livingood's
      advice to look beyond the borders in our lives.

PMID- 18319018
TI  - Pattern of non-venereal dermatoses of female external genitalia in South India.
AB  - Non-venereal dermatoses tend to be confused with venereal diseases, which may be
      responsible for mental distress and guilt feelings in patients. We conducted the
      study to find the pattern of non-venereal dermatoses of female external genitalia
      and to correlate non-venereal dermatoses with various clinical parameters. The
      study included 120 female patients with non-venereal dermatoses of female
      external genitalia presenting over a period of 22 months from September 2005 to
      June 2007. The demographic characteristics and clinical findings were recorded.
      Cases having venereal diseases were excluded from the study. A total of nineteen
      non-venereal dermatoses were noted in the study. The most common non-venereal
      dermatoses were lichen sclerosus (26 cases or 21.7%), vitiligo (19 cases or
      15.8%), lichen simplex chronicus (16 cases or 13.3%), and vulval candidiasis (11
      or 9.2%). Other dermatoses included lymphedema, invasive squamous cell carcinoma,
      tinea cruris, psoriasis, furuncle, folliculitis, lichen planus, epidermal
      inclusion cyst, herpes zoster, irritant contact dermatitis, acrochordon,
      Bartholin cyst, fibroepithelial stromal polyp, molluscum contagiosum
      (autoinoculated), and streptococcal vulvitis. This study highlights the
      importance of diagnosing non-venereal dermatoses and refutes the general
      misconception that all vulval itching is the result of fungal infection. The two
      most common causes of vulval itching observed in the study were lichen sclerosus
      and lichen simplex chronicus.

PMID- 18319019
TI  - Vulvodynia.
AB  - Vulvodynia or vulvar pain syndrome is a chronic, heterogeneous, and
      multifactorial disease with a high prevalence. This condition affects Caucasians,
      African Americans, Africans and Hispanic women, particularly those sexually
      active at child-bearing age. The etiology of this condition is complex and
      remains elusive. An accurate diagnosis requires a comprehensive history, physical
      examination and targeted diagnostic tests. Although many treatment options have
      been utilized, a rational therapeutic strategy is still under research.
      Psychological counseling and group support should be considered in all cases.

PMID- 18319020
TI  - Poromatosis: the occurrence of multiple eccrine poromas.
AB  - Eccrine poromas are rare, benign adnexal tumors derived from the intraepidermal
      portion of sweat ducts. Historically they were thought to arise from eccrine
      ducts although today it is thought that they may also have an apocrine origin.
      They usually appear as solitary, slow-growing, skin-colored papules on acral
      surfaces. Here we present the unusual situation of a patient with multiple
      poromas only three of which are located near the distal extremities.

PMID- 18319021
TI  - Pilomatrical carcinoma: a case in a patient with HIV and hepatitis C.
AB  - Pilomatrical carcinoma is a rare tumor without a single pathognemonic feature
      that distinguishes it from the benign pilomatricoma. We report a 51-year-old man
      with HIV, hepatitis C, and pilomatrical carcinoma.

PMID- 18319022
TI  - Mycobacterium mucogenicum: report of a skin infection associated with etanercept.
AB  - Mycobacterium mucogenicum is a recently characterized organism that rarely may
      cause human infections. This rapidly growing mycobacterium is commonly identified
      in tap water. Both immunosuppressed and immunocompetent patients may develop
      infections from Mycobacterium mucogenicum. Some patients have experienced lethal
      disease, including sepsis. Infections occurring in the skin and soft tissues have
      been described only after a preceding injury. We present the first case of
      infection with Mycobacterium mucogenicum occurring in a patient on the TNF-alpha
      antagonist etanercept and without any prior soft tissue injury.

PMID- 18319023
TI  - An unusual presentation of atypical fibroxanthoma.
AB  - Atypical fibroxanthoma (AFX) is a rare cutaneous spindle-cell neoplasm. The tumor
      occurs most commonly in sun-damaged skin of the head and neck in elderly
      patients. A small subset of patients (approximately one in five cases) is middle
      aged and presents with AFX of the trunk or extremities in areas without evidence
      of actinic damage. We report an unusual case of AFX of the lower leg in an 81
      year-old woman with extensive actinic damage.

PMID- 18319024
TI  - Melkersson Rosenthal syndrome associated with ipsilateral facial, hand, and foot
      swelling.
AB  - Melkersson-Rosenthal syndrome is a complex neuromucocutaneous disorder. A 60-year
      old woman presented with granulomatous cheilitis of the lower lip, unilateral
      facial paralysis, and ipsilateral facial and acral swelling. The result of
      histopathological evaluation in extremities and inferior lip was compatible with
      Melkersson-Rosenthal syndrome.

PMID- 18319025
TI  - Blepharochalasis--a rare entity.
AB  - We report a case of a 9-year-old boy with blepharochalasis, who had recurrent
      angioedema along with wrinkling of the skin of the upper eyelids since age 5
      years. The systemic examination of the patient was normal. The patient was
      diagnosed as a typical case of blepharochalasis. Although the normal age to
      develop blepharochalasis is at puberty, our patient developed it, which is rare.

PMID- 18319026
TI  - Bardet-Biedl syndrome: a case report.
AB  - Bardet-Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive
      disorder characterized by progressive retinal dystrophy, polydactyly, obesity,
      hypogonadism, mental retardation, and renal dysfunction. Other manifestations
      include diabetes mellitus, heart disease, hepatic fibrosis, neurological
      features, and multiple pigmented nevi. To date, twelve BBS genes have been cloned
      (BBS1-BBS12). Herein we discussed a patient with BBS who had multiple pigmented
      nevi.

PMID- 18319027
TI  - Calcinosis cutis: a rare feature of adult dermatomyositis.
AB  - Dermatomyositis is an idiopathic inflammatory myopathy with characteristic
      cutaneous manifestations. We describe a case of a 55-year-old woman with
      dermatomyositis who presented with dystrophic calcinosis resistant to medical
      treatment.

PMID- 18319028
TI  - Multiple lentigines arising in resolving psoriatic plaques after treatment with
      etanercept.
AB  - Development of lentigines in zones previously affected by plaques of psoriasis
      has been described, and its frequency has probably been underestimated. Most
      cases have been described following the use of phototherapy, although other
      authors have observed the appearance of lentigines in patients with psoriasis
      treated only with topical products. It has been suggested that the mechanism
      involved could be an abnormal reaction to UV light or an unusual form of
      postinflammatory hyperpigmentation. We report the case of two patients in whom
      multiple lentigines appeared, confined to plaques of psoriasis after using
      etanercept. Development of lentigines after using biologic drugs is a phenomenon
      that does not appear to have been described previously. We consider that the
      mechanism of production of lentigines is related to psoriasis itself and not to
      the therapy used.

PMID- 18319029
TI  - Sudden onset of verrucous plaques to the face and trunk: a case of reactivation
      cutaneous histoplasmosis in the setting of HIV.
AB  - A 66-year-old Columbian man presented with a 15-day history of generalized
      weakness, cough, fever, and verrucous, ulcerating plaques of the face, upper
      chest, upper back, and arms. The patient proved to be HIV positive.
      Histopathologic examination showed a diffuse lymphocytic infiltrate coupled with
      a striking number of yeast forms within macrophages. The clinical presentation
      and histopathologic alterations are consistent with the diagnosis disseminated
      Histoplasma capsulatum. This case emphasizes the importance of increasing
      awareness of histoplasmosis in nonendemic areas as a result of the large subgroup
      of immunocompromised patients at risk. Disseminated histoplasmosis can be a
      treatable HIV complication if recognized early, although is unfortunately a
      harbinger for an overall poor prognosis.

PMID- 18319030
TI  - Post traumatic amelanotic subungual melanoma.
AB  - Subungual melanomas are rare; a delay in the diagnosis is common and is
      associated with advanced stage. Part of the reason for a delay in presentation to
      the physician is that patients often attribute the lesion to trauma. Trauma may
      play a role in the pathogenesis or just draw attention to a skin tumor that may
      be more susceptible to injury. We report a case of subungual melanoma that was
      observed in an 86 year old man. The preceding trauma history and misleading
      clinical appearance delayed the diagnosis slightly. Biopsy of every nodular acral
      tumor is very important. A direct role of the trauma in the pathogenesis of
      melanoma remains unclear.

PMID- 18319031
TI  - Solid facial edema: treatment failure with oral isotretinoin monotherapy and
      combination oral isotretinoin and oral steroid therapy.

PMID- 18319032
TI  - Pigmented nodular hidradenoma masquerading as nodular malignant melanoma.

PMID- 18319033
TI  - Hereditary leiomyomatosis and renal cell carcinoma syndrome: a case report.
AB  - The simultaneous occurrence of multiple cutaneous leiomyomas, uterine
      leiomyomatosis, and renal cancer is described as a cancer syndrome with an
      autosomal dominant pattern of inheritance. We report a 79-year-old man who
      presented with multiple hyperkeratotic, erythematous nodules on his right leg
      with a histological diagnosis of pilar leiomyoma. In a review of systems, gross
      hematuria, weight loss, and bone pain were noted. His pathologic diagnosis was
      determined to be metastatic papillary renal cell carcinoma. A family history
      revealed that his sister had a hysterectomy for uterine leiomyomas. The findings
      in this case can be attributed to hereditary leiomyomatosis and renal cell
      carcinoma syndrome.

PMID- 18319034
TI  - Oral melanoma: an unusual presentation.
AB  - Melanoma of the oral cavity is a rare malignant disease that is often discovered
      in an advanced stage; survival time is an average of five years. Oral melanoma
      makes up from 0.2 to 8 percent of all melanomas. The presentation of this
      clinical case demonstrates the complexity of clinical and histopathological
      manifestations and poor prognosis of oral melanoma.

PMID- 18319035
TI  - Pagetoid reticulosis of Woringer-Kolopp.
AB  - Pagetoid reticulosis of Woringer-Kolopp is a rare form of cutaneous T-cell
      lymphoma that primarily affects middle-aged males. It is characterized by the
      presence of one or several scaly patches and plaques with an acral distribution.
      We present a case of a 58-year-old woman, otherwise healthy, with a 5-month
      history of asymptomatic, hyperkeratotic plaques on the hands and feet.
      Histological and immunohistochemical analysis confirmed the diagnosis. Nearly
      complete spontaneous regression was noted 7 months after the initial examination.
      After 5 years no evidence of the disease remained.

PMID- 18319036
TI  - Shah-Waardenburg syndrome.
AB  - A case of Shah-Waardenburg syndrome, a rare variant of Waardenburg syndrome, is
      presented. Inherited as an autosomal recessive or dominant trait, the disorder
      presumably results from defective migration of neural crest cells. It clinically
      manifests with pigmentary anomalies and congenital megacolon.

PMID- 18319037
TI  - Tripod vibration anesthesia.
AB  - Cutaneous vibrators have been introduced to relieve pain associated with a
      variety of dermatology procedures including injections and laser treatments. The
      simple tripod massager described in this report is effective and acceptable to
      patients for cutaneous injection anesthesia.

PMID- 18319038
TI  - Dermatitis herpetiformis: potential for confusion with linear IgA bullous
      dermatosis on direct immunofluorescence.

PMID- 18319039
TI  - Dermatology misnomers.

PMID- 18319040
TI  - Which cyclic antidepressants are superior for the treatment of depressed
      psoriatic patients? A theoretical molecular approach.

PMID- 18319041
TI  - Unilateral laterothoracic exanthem with coincident evidence of Epstein-Barr virus
      reactivation: exploration of a possible link.

PMID- 18319042
TI  - Exanthematous allergic drug reactions due to four chemically unrelated drugs.

PMID- 18319044
TI  - MD/PhDs are more likely than MDs to choose a career in academic dermatology.
AB  - There are fewer dermatologists entering and being retained in academics. We
      investigated the hypothesis that MD/PhDs are more likely than MDs to enter a
      career in academic dermatology. This retrospective study of university
      dermatology departments and divisions studied MDs, DOs, and MD/PhDs who completed
      a dermatology program in the U.S. and were serving as full-time dermatology
      faculty members at a US dermatology program as of December 2004. The main outcome
      measures were percentage of MD/PhDs who chose a career in academics compared to
      the percentage of MDs who chose a career in academics; MDs, DOs, MD/PhDs and
      serving as full-time faculty members and the number serving as chair or chief of
      dermatology. The total number of MD/PhDs and percentage of MD/PhDs as full-time
      faculty in 107 U.S. dermatology programs were determined. As of December 2004,
      there were 782 full-time faculty MDs who completed a residency in the US, with 72
      (9.2%) MD/PhDs who completed a US dermatology residency program. MD/PhDs were
      1.63 times (p < or =0.001) more likely to go into academics compared to MDs. The
      programs with the highest number of MD/PhDs as full-time faculty and the programs
      with the highest percentage of MD/PhDs as full-time faculty were tabulated. Seven
      out of an eligible 101 dermatology chiefs/chairs were MD/PhDs. The assumption
      that 5.8 percent of dermatology residents who were MD/PhD during 2004-2007 could
      be extrapolated to the 35 year period of 1970-2004. MD/PhDs are an important
      source of physician-scientists in academic dermatology and were 1.63 times more
      likely compared to MDs to choose a career in academics and remain in academics.

PMID- 18319045
TI  - Sunburn risk factors for beachgoing children.
AB  - Sunburn prevention in children and the early establishment of sun protective
      behavior is predicted to result in a decreased future incidence of skin cancer. A
      survey of beachgoing families was conducted to evaluate the parental/guardian
      role in the use of sun protection for their minor children. Ethnicity and
      Fitzpatrick Skin Type of children and their parents were the best predictors for
      sunburn. White, non-Hispanic children were 7.8 times more likely to have a
      history of sunburn than children whose parents identified them as Hispanic when
      controlled for the same Fitzpatrick Skin Types.

PMID- 18319046
TI  - Identifying residents who will choose academic dermatology.

PMID- 18319047
TI  - Risk and timing of neutropenic events in adult cancer patients receiving
      chemotherapy: the results of a prospective nationwide study of oncology practice.
AB  - This study was undertaken to describe the relationship between the occurrence and
      timing of neutropenic events and chemotherapy treatment in a community-based
      population of patients with cancer. The study included 2962 patients with breast,
      lung, colorectal, lymphoma, and ovarian cancers from a prospective U.S. registry
      of patients initiating a new chemotherapy regimen. Detailed patient-, disease-,
      and treatment-related data, including toxicities, were captured at baseline, the
      beginning of each cycle, and each midcycle blood draw for up to 4 cycles of
      treatment. Primary outcomes included febrile neutropenia (FN), severe neutropenia
      without fever/ infection, and relative dose intensity (RDI). Thirty-seven percent
      of patients were aged 65 years or older, 43.5% had an Eastern Cooperative
      Oncology Group performance status of 1 or greater, and 27% had 1 or more
      comorbidities. Reductions in RDI to less than 85% of standard in the first cycle
      were planned in 23.6% of patients, whereas primary colony-stimulating factor
      prophylaxis was used in 18.2%. In the first 3 cycles of treatment, 10.7% of
      patients experienced FN, with most of these events (58.9%) occurring in the first
      cycle. This first-cycle pattern was consistently observed despite wide variations
      in event rates by tumor type, disease stage, chemotherapy regimen and dose, and
      patient characteristics. Despite frequent planned reductions from standard RDI,
      the incidence of FN remains high in community oncology practice in the United
      States. Improved methods of pretreatment assessment of patient risk factors for
      neutropenia are needed.

PMID- 18319048
TI  - Prevention and treatment of cancer-related infections.

PMID- 18319049
TI  - Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for
      invasive mold infections: point.
AB  - Invasive fungal infections (IFIs) are a leading cause of infection-related
      mortality in patients with acute leukemia and prolonged neutropenia and in
      allogeneic hematopoietic stem cell transplant (HSCT) recipients with graft-versus
      host disease (GVHD). Although invasive candidiasis was the principal IFI
      predating fluconazole prophylaxis, invasive aspergillosis and other mold
      infections now cause most deaths from fungal infection in this patient
      population. The availability of broad-spectrum antifungal agents that can be
      safely administered over prolonged periods has stimulated interest in using mold
      active prophylactic agents early as prophylaxis rather than later as therapy for
      suspected or documented IFIs. Two recent, prospective, randomized trials have
      shown a clear benefit of posaconazole prophylaxis in patients with
      myelodysplastic syndrome and acute mye-logenous leukemia with prolonged
      neutropenia and in allogeneic HSCT recipients with severe GVHD. In contrast, the
      peer-reviewed published database on the strategy of preemptive antifungal
      therapy, in which yeast-active prophylaxis (fluconazole) or no antifungal
      prophylaxis is used initially and modifications are triggered by a combination of
      laboratory markers and chest CT scans, is currently limited to an open-label
      feasibility study. Does sufficient evidence currently exist that the net benefit
      of the preemptive approach is at least on a par with posaconazole prophylaxis in
      the specific patient groups that were studied? The authors believe not and that
      more research is needed before the preemptive strategy can be recommended.

PMID- 18319050
TI  - Broad-spectrum antifungal prophylaxis in patients with cancer at high risk for
      invasive mold infections: counterpoint.
AB  - Management of invasive mold infections in patients with prolonged neutropenia and
      hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host
      disease (GVHD) has been hampered by the difficulty in diagnosing these
      infections. Definite diagnosis invariably centers on histologic identification of
      hyphae in tissue or on culture from a sterile body site. Therefore, most
      practitioners have relied on prophylaxis and empiric therapy. Currently, emphasis
      is shifting from routine prophylaxis and empiric therapy to screening of patients
      with neutropenia at high risk so that clinicians can administer appropriate
      antifungal therapy early, when it can potentially improve patient outcome. Non
      culture-based microbiologic tools are at the forefront of this paradigm shift.
      Commercially available methods to detect fungal antigens and sophisticated
      techniques to detect fungal DNA may be used as screening tools during the highest
      risk period. Together with assessment of clinical signs, cultures, and especially
      CT scanning, these methods are useful for starting antifungal therapy
      preemptively. While awaiting further evaluation of these tools during the
      postengraftment period of allogeneic HSCT, mold-active prophylaxis targeting the
      subgroup of patients with severe acute or chronic GVHD may be justified. However,
      some critical issues have not yet been adequately addressed, including the
      generalizability of study results, impact of mucositis and gastrointestinal GVHD
      on drug bioavailability, need for therapeutic drug monitoring, impact of
      prophylaxis on the performance of diagnostic assays, and optimal treatment of
      breakthrough invasive fungal infections.

PMID- 18319051
TI  - Prevention and early treatment of opportunistic viral infections in patients with
      leukemia and allogeneic stem cell transplantation recipients.
AB  - A leading complication of leukemia therapy and stem cell transplantation is
      opportunistic viral infections. Infections caused by cytomegalovirus, herpes
      simplex, varicella-zoster, Epstein-Barr, and the community respiratory viruses
      are associated with significant morbidity and mortality in this highly
      immunosuppressed population. Fortunately, a growing armamentarium is allowing
      more effective prophylaxis of these pathogens. This article reviews the
      epidemiology and prophylactic strategies available for these common opportunistic
      viral pathogens.

PMID- 18319052
TI  - Infectious complications associated with immunomodulating monoclonal antibodies
      used in the treatment of hematologic malignancy.
AB  - Immunomodulating monoclonal antibodies are a relatively new addition to the
      armamentarium of cancer therapeutics and have been shown to improve clinical
      outcomes in patients with various hematologic malignancies. Because of their
      targeted nature, these agents are often believed to be less immunosuppressive
      than standard cytotoxic chemotherapeutic agents. A clear causal association
      between an immunomodulating therapy and its infectious sequelae is often
      difficult to discern because of the burden of comorbid illness, intrinsic
      immunosuppression from the underlying malignancy, use in the salvage setting, and
      prior and concomitant use of immunosuppressive agents in this patient population.
      This article evaluates better-established and anecdotal infectious complications
      associated with major immunomodulating therapies used in hematologic malignancy
      and hematopoietic stem cell transplantation, including rituximab, alemtuzumab,
      gemtuzumab ozogamicin, infliximab, dacluzimab, and basiliximab.

PMID- 18319053
TI  - Influenza: preparedness for an inevitable "Emergency" for oncology and BMT units.
AB  - Influenza is a seasonal and pandemic threat to the general population. The
      effects can be devastating for cancer patients and those who have undergone blood
      and marrow transplantation (BMT). However, this impact can be minimized.
      Emergency preparedness is the key to mitigating the impact on the oncology and
      BMT services. Having a plan that provides a framework of preparedness and
      outlines steps to take in the event of a community outbreak is crucial. A
      vigorous immunization campaign for patients, household contacts, and health care
      staff early in the season is the single most important action. In the midst of an
      outbreak, the oncology and BMT teams should act to quickly identify patients with
      suspected infections, move infected patients and staff away from noninfected
      patients to prevent contact, and decide which patients require prevention or
      treatment with antiviral agents. Ongoing engagement by the entire team to
      evaluate the effectiveness of its actions and modify its plan as necessary will
      ensure success.

PMID- 18319054
TI  - The link between IL-23 and Th17 cell-mediated immune pathologies.
AB  - IL-23--produced by dendritic cells--and Th17 cells have both been identified as
      major factors involved in autoimmune inflammation, yet their relationship with
      each other remains controversial. This review aims to describe the initial
      discovery of Th17 cells, their subsequent characterization as a unique T helper
      subset in mouse and man, as well as the mechanisms involved in regulating these
      cells. Finally, the roles of IL-23 in inflammatory diseases in relation to Th17
      function will be discussed.

PMID- 18319055
TI  - The proximal N-terminal amino acid residues are required for the coupling
      activity of the bovine heart mitochondrial factor B.
AB  - Treatment of the recombinant bovine factor B with trypsin yielded a fragment
      (amino acid residues 62-175) devoid of coupling activity. Removal of the N
      terminal Trp2-Gly3-Trp4 peptide resulted in a significant loss of coupling
      activity in the FB(DeltaW)(2)(-W)(4) deletion mutant. Sucrose density gradient
      centrifugation demonstrated co-sedimentation of recombinant factor B with the
      ADP/ATP carrier, which is present in preparations of H(+)-translocating F(0)F(1)
      ATPase, but not in preparations of complex V. The N-terminally truncated factor B
      mutant FB(DeltaW)(2)(-W)(4) did not co-sediment with the ADP/ATP carrier.
      Recombinant factor B co-sedimented with partially purified membrane sector F(0),
      extracted from F(1)-stripped bovine submitochondrial particles with n-dodecyl
      beta-d-maltoside. Factor B inhibited the passive proton conductance catalyzed by
      F(0) reconstituted into asolectin liposomes. A factor B mutant, bearing a
      photoreactive unnatural amino acid pbenzoyl-l-phenylalanine (pBpa) substituted
      for Trp2, cross-linked with F(0) subunits e and g as well as the ADP/ATP carrier.
      These results suggest that the N-terminal domain and, in particular, the proximal
      N-terminal amino acids are important for the coupling activity and protein
      protein interactions of bovine factor B.

PMID- 18319056
TI  - WITHDRAWN: Generation of F0F1-ATPase nanoarray by Dip-Pen Nanolithography and its
      application as biosensor.
AB  - This article has been withdrawn consistent with Elsevier Policy on Article
      Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher
      apologizes for any inconvenience this may cause.

PMID- 18319057
TI  - An efficient and convenient synthesis of deuterium-labelled seminolipid
      isotopomers and their ESI-MS characterization.
AB  - Seminolipids 1a and 1b and galactosylalkylacylglycerols 2a and 2b, labelled with
      deuterium on the alkyl or acyl chain, respectively, were obtained isotopically
      and chemically pure through a straightforward synthesis from protected glycidyl
      galactoside 3 in an overall 22% yield. The identity and purity of compounds was
      ascertained by NMR spectroscopy and ESI mass spectrometry analysis. These
      labelled compounds are important as internal standards for quantification of
      these lipids by mass spectrometry, and they could also be used in metabolic
      studies in in vitro and even in vivo systems. Extension of the procedure could
      provide a route for the preparation of isotopomers of other compounds of the same
      general class.

PMID- 18319058
TI  - Pharmacokinetics of the new proton pump inhibitor ilaprazole in Chinese healthy
      subjects in relation to CYP3A5 and CYP2C19 genotypes.
AB  - BACKGROUND: PPIs are widely used in peptic diseases, and this paper is to
      investigate the kinetic characteristics of a new PPI ilaprazole in Chinese
      healthy subjects and the association with CYP3A5 and CYP2C19 polymorphisms.
      METHODS: 21 subjects were selected and treated with 10mg ilaprazole according to
      their CYP3A5*3 genotypes (including 7 of CYP3A5*1/*1, 7 of *1/*3, and 7 of
      *3/*3). The plasma concentrations of ilaprazole and its metabolites were
      monitored by LC-MS/MS method. RESULTS: The C(max), AUC((0-6)), AUC((0-48)) and
      AUC((0-infinity)) of ilaprazole were all significantly different across the 3
      CYP3A5 genotypes (including 4 of CYP3A5*1/*1, 4 of *1/*3, 3 of *3/*3; P<0.05) in
      CYP2C19 wild-type subjects (CYP2C19 wt/wts), similar variety of C(max) and AUC((0
      6)) among CYP3A5 genotypes (including 3 of CYP3A5*1/*1, 3 of *1/*3, 4 of *3/*3;
      P<0.05) were also observed in CYP2C19 heterozygous subjects (CYP2C19 wt/mts). The
      sulfoxidation metabolic index (measure of collective CYP3A activity) indicates
      that the CYP3A5*1/*1, (high-expressers), *1/*3, (low-expressers), and *3/*3 (no
      expressers) groups have medium, lowest and highest activities on ilaprazole
      metabolism, inconsistent with genotype-based CYP3A5 enzymatic activity. Further
      analysis showed no correlation between ilaprazole metabolism and CYP2C19
      genotypes, evidenced by that the AUC((0-infinity)) of ilaprazole from either
      CYP3A5*1/*1 or CYP3A5*1/*3 groups was much higher in CYP2C19 wt/wts (n=4) than
      that in CYP2C19 wt/mts (n=3) (P<0.001), but the C(max) and AUC((0-6)) of
      ilaprazole from CYP3A5*3/*3 groups, were significantly lower in CYP2C19 wt/wts
      (n=3) compared to CYP2C19 wt/mts (n=4) (P<0.01). CONCLUSIONS: There was no
      demonstrated relationship between ilaprazole metabolism and CYP3A5 polymorphisms.

PMID- 18319059
TI  - Residue 134 determines the dimer-tetramer assembly of nucleoside diphosphate
      kinase from moderately halophilic bacteria.
AB  - Halomonas nucleoside diphosphate kinase (HaNDK) forms a dimeric assembly and
      Pseudomonas NDK (PaNDK) forms a tetrameric assembly. The mutation of Glu134 to
      Ala in HaNDK resulted in the conversion of the native dimeric structure to the
      tetramer assembly. Conversely, the mutation of Ala134 to Glu in PaNDK lead to the
      conversion from the tetramer to the dimer assembly, indicating that a single
      amino acid substitution at position 134 results in an alteration of the
      oligomeric structure of NDK. By modeling the structure of HaNDK and PaNDK based
      on the crystal structure of Myxococcus NDK, we showed that Glu134 exerts
      sufficient repulsive forces to disrupt the dimer-dimer interaction and prevent
      the formation of the tetramer.

PMID- 18319060
TI  - Evidence for a novel phosphopantetheinyl transferase domain in the polyketide
      synthase for enediyne biosynthesis.
AB  - The polyketide synthase associated with the biosynthesis of enediyne-containing
      calicheamicin contains a putative phosphopantetheinyl transferase (PPTase)
      domain. By cloning and expressing the C-terminal region of the polyketide
      synthase and in vitro phosphopantetheinylation assay, we found that the PPTase
      domain exhibits preferred substrate specificity towards acyl and peptidyl carrier
      proteins in fatty acid and non-ribosomal peptide synthesis over its cognate
      partner. We also found evidence suggesting that the PPTase domain adopts a pseudo
      trimeric structure, distinct from the pseudo-dimeric structure of type II
      PPTases. The results revealed a novel type of PPTase with unique structure and
      substrate specificity, and suggested that the polyketide synthase probably
      acquired the PPTase domain from a primary metabolic pathway in evolution.

PMID- 18319061
TI  - Lysine 263 residue of NPM/B23 is essential for regulating ATP binding and B23
      stability.
AB  - Here, we show that Nucleophsomin/B23 provides lysine 263 as a critical binding
      site for ATP. Mutagenesis of lysine 263 to asparagine (K263N) disrupts B23 from
      ATP binding. While B23 WT exclusively localizes to the nucleolus, the B23-K263N
      is redistributed from the nucleolus to the nucleoplam. Notably, the K263N mutant
      is unstable, and displayed rapid degradation. Alteration of K263 induced B23
      instability through increased ubiquitination and proteaosomal degradation.
      Moreover, mutation of K263 impedes the mitogenic effect of B23 in PC12 cells.
      Thus, K263 is a critical site for ATP binding and required for B23 stability,
      confining B23 in the nucleolus.

PMID- 18319062
TI  - IFNgamma enhances IL-23 production during Francisella infection of human
      monocytes.
AB  - We previously demonstrated that monocytes produce IL-23 during Francisella
      infection, and that IL-23 induces IFNgamma from NK cells. Here, we demonstrate
      that IFNgamma-priming of monocytes enhances IL-23 production during Francisella
      infection. This effect was seen on the IL12/23 p40 subunit. Induction of IL-12/23
      p40 is reported to be enhanced by IRF-1 and IRF-8. Consistently, microarray
      analysis of IFNgamma-treated monocytes revealed a significant induction of the
      IRFs. Interestingly, IFNgamma-primed monocytes produced IL-12 p70, a more potent
      inducer of IFNgamma than IL-23. We propose that there exists an amplification
      loop between monocyte IL-23 and NK/T cell IFNgamma that leads to IL-12 p70
      production.

PMID- 18319063
TI  - Site-directed mutagenesis studies of acetylglutamate synthase delineate the site
      for the arginine inhibitor.
AB  - N-acetyl-L-glutamate synthase (NAGS), the first enzyme of bacterial/plant
      arginine biosynthesis and an essential activator of the urea cycle in animals,
      is, respectively, arginine-inhibited and activated. Site-directed mutagenesis of
      recombinant Pseudomonas aeruginosa NAGS (PaNAGS) delineates the arginine site in
      the PaNAGS acetylglutamate kinase-like domain, and, by extension, in human NAGS.
      Key residues for glutamate binding are identified in the acetyltransferase
      domain. However, the acetylglutamate kinase-like domain may modulate glutamate
      binding, since one mutation affecting this domain increases the K(m) for
      glutamate. The effects on PaNAGS of two mutations found in human NAGS deficiency
      support the similarity of bacterial and human NAGSs despite their low sequence
      identity.

PMID- 18319065
TI  - Roles of l-serine and sphingolipid synthesis in brain development and neuronal
      survival.
AB  - Sphingolipids represent a class of membrane lipids that contain a hydrophobic
      ceramide chain as its common backbone structure. Sphingolipid synthesis requires
      two simple components: l-serine and palmitoyl CoA. Although l-serine is
      classified as a non-essential amino acid, an external supply of l-serine is
      essential for the synthesis of sphingolipids and phosphatidylserine (PS) in
      particular types of central nervous system (CNS) neurons. l-Serine is also
      essential for these neurons to undergo neuritogenesis and to survive. Biochemical
      analysis has shown that l-serine is synthesized from glucose and released by
      astrocytes but not by neurons, which is the major reason why this amino acid is
      an essential amino acid for neurons. Biosynthesis of membrane lipids, such as
      sphingolipids, PS, and phosphatidylethanolamine (PE), in neurons is completely
      dependent on this astrocytic factor. Recent advances in lipid biology research
      using transgenic mice have demonstrated that synthesis of endogenous l-serine and
      neuronal sphingolipids is essential for brain development. In this review, we
      discuss the metabolic system that coordinates sphingolipid synthesis with the l
      serine synthetic pathway between neurons and glia. We also discuss the crucial
      roles of the metabolic conversion of l-serine to sphingolipids in neuronal
      development and survival. Human diseases associated with serine and sphingolipid
      biosynthesis are also discussed.

PMID- 18319066
TI  - Natural causes of programmed death of yeast Saccharomyces cerevisiae.
AB  - The existence of cell death program in unicellular organisms has been reported
      for a number of species. Nevertheless, the question why the ability to commit
      suicide has been maintained throughout evolution is far from being solved. While
      it is believed that altruistic death of individual yeast cells could be
      beneficial for the population, it is generally not known (i) what is wrong with
      the individuals destined for elimination, (ii) what is the critical value of the
      parameter that makes a cell unfit and (iii) how the cell monitors this parameter.
      Studies performed on yeast Saccharomyces cerevisiae allow us to hypothesize on
      ways of possible solutions of these problems. Here we argue that (a) the main
      parameter for life-or-death decision measured by the cell is the degree of damage
      to the genetic material, (b) its critical value is dictated by quorum sensing
      machinery, and (c) it is measured by monitoring delays in cell division.

PMID- 18319067
TI  - The impact of mitochondrial tRNA mutations on the amount of ATP synthase differs
      in the brain compared to other tissues.
AB  - The impact of point mutations in mitochondrial tRNA genes on the amount and
      stability of respiratory chain complexes and ATP synthase (OXPHOS) has been
      broadly characterized in cultured skin fibroblasts, skeletal muscle samples, and
      mitochondrial cybrids. However, less is known about how these mutations affect
      other tissues, especially the brain. We have compared OXPHOS protein deficiency
      patterns in skeletal muscle mitochondria of patients with Leigh (8363G>A), MERRF
      (8344A>G), and MELAS (3243A>G) syndromes. Both mutations that affect mt-tRNA(Lys)
      (8363G>A, 8344A>G) resulted in severe combined deficiency of complexes I and IV,
      compared to an isolated severe defect of complex I in the 3243A>G sample (mt
      tRNA(LeuUUR). Furthermore, we compared obtained patterns with those found in the
      heart, frontal cortex, and liver of 8363G>A and 3243A>G patients. In the frontal
      cortex mitochondria of both patients, the patterns of OXPHOS deficiencies
      differed substantially from those observed in other tissues, and this difference
      was particularly striking for ATP synthase. Surprisingly, in the frontal cortex
      of the 3243A>G patient, whose ATP synthase level was below the detection limit,
      the assembly of complex IV, as inferred from 2D-PAGE immunoblotting, appeared to
      be hindered by some factor other than the availability of mtDNA-encoded subunits.

PMID- 18319068
TI  - Structural and functional characterization of osmotically inducible protein C
      (OsmC) from Thermococcus kodakaraensis KOD1.
AB  - Osmotically inducible protein C (OsmC) is involved in the cellular defense
      mechanism against oxidative stress caused by exposure to hyperoxides or elevated
      osmolarity. OsmC was identified by two-dimensional electrophoresis (2DE) analysis
      as a protein that is overexpressed in response to osmotic stress, but not under
      heat and oxidative stress. Here, an OsmC gene from T. kodakaraensis KOD1 was
      cloned and expressed in Escherichia coli. TkOsmC showed a homotetrameric
      structure based on gel filtration and electron microscopic analyses. TkOsmC has a
      significant peroxidase activity toward both organic and inorganic peroxides in
      high, but not in low temperature.

PMID- 18319070
TI  - A critical appraisal of the scientific basis of commercial genomic profiles used
      to assess health risks and personalize health interventions.
AB  - Predictive genomic profiling used to produce personalized nutrition and other
      lifestyle health recommendations is currently offered directly to consumers. By
      examining previous meta-analyses and HuGE reviews, we assessed the scientific
      evidence supporting the purported gene-disease associations for genes included in
      genomic profiles offered online. We identified seven companies that offer
      predictive genomic profiling. We searched PubMed for meta-analyses and HuGE
      reviews of studies of gene-disease associations published from 2000 through June
      2007 in which the genotypes of people with a disease were compared with those of
      a healthy or general-population control group. The seven companies tested at
      least 69 different polymorphisms in 56 genes. Of the 56 genes tested, 24 (43%)
      were not reviewed in meta-analyses. For the remaining 32 genes, we found 260 meta
      analyses that examined 160 unique polymorphism-disease associations, of which
      only 60 (38%) were found to be statistically significant. Even the 60 significant
      associations, which involved 29 different polymorphisms and 28 different
      diseases, were generally modest, with synthetic odds ratios ranging from 0.54 to
      0.88 for protective variants and from 1.04 to 3.2 for risk variants. Furthermore,
      genes in cardiogenomic profiles were more frequently associated with
      noncardiovascular diseases than with cardiovascular diseases, and though two of
      the five genes of the osteogenomic profiles did show significant associations
      with disease, the associations were not with bone diseases. There is insufficient
      scientific evidence to conclude that genomic profiles are useful in measuring
      genetic risk for common diseases or in developing personalized diet and lifestyle
      recommendations for disease prevention.

PMID- 18319071
TI  - Multipoint approximations of identity-by-descent probabilities for accurate
      linkage analysis of distantly related individuals.
AB  - We propose an analytical approximation method for the estimation of multipoint
      identity by descent (IBD) probabilities in pedigrees containing a moderate number
      of distantly related individuals. We show that in large pedigrees where cases are
      related through untyped ancestors only, it is possible to formulate the hidden
      Markov model of the Lander-Green algorithm in terms of the IBD configurations of
      the cases. We use a first-order Markov approximation to model the changes in this
      IBD-configuration variable along the chromosome. In simulated and real data sets,
      we demonstrate that estimates of parametric and nonparametric linkage statistics
      based on the first-order Markov approximation are accurate. The computation time
      is exponential in the number of cases instead of in the number of meioses
      separating the cases. We have implemented our approach in the computer program
      ALADIN (accurate linkage analysis of distantly related individuals). ALADIN can
      be applied to general pedigrees and marker types and has the ability to model
      marker-marker linkage disequilibrium with a clustered-markers approach. Using
      ALADIN is straightforward: It requires no parameters to be specified and accepts
      standard input files.

PMID- 18319069
TI  - The involvement of DNA-damage and -repair defects in neurological dysfunction.
AB  - A genetic link between defects in DNA repair and neurological abnormalities has
      been well established through studies of inherited disorders such as ataxia
      telangiectasia and xeroderma pigmentosum. In this review, we present a
      comprehensive summary of the major types of DNA damage, the molecular pathways
      that function in their repair, and the connection between defective DNA-repair
      responses and specific neurological disease. Particular attention is given to
      describing the nature of the repair defect and its relationship to the
      manifestation of the associated neurological dysfunction. Finally, the review
      touches upon the role of oxidative stress, a leading precursor to DNA damage, in
      the development of certain neurodegenerative pathologies, such as Alzheimer's and
      Parkinson's.

PMID- 18319072
TI  - CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and
      seizures.
AB  - Coenzyme Q(10) (CoQ(10)) plays a pivotal role in oxidative phosphorylation
      (OXPHOS) in that it distributes electrons between the various dehydrogenases and
      the cytochrome segments of the respiratory chain. Primary coenzyme Q(10)
      deficiency represents a clinically heterogeneous condition suggestive of genetic
      heterogeneity, and several disease genes have been previously identified. The
      CABC1 gene, also called COQ8 or ADCK3, is the human homolog of the yeast
      ABC1/COQ8 gene, one of the numerous genes involved in the ubiquinone biosynthesis
      pathway. The exact function of the Abc1/Coq8 protein is as yet unknown, but this
      protein is classified as a putative protein kinase. We report here CABC1 gene
      mutations in four ubiquinone-deficient patients in three distinct families. These
      patients presented a similar progressive neurological disorder with cerebellar
      atrophy and seizures. In all cases, enzymological studies pointed to ubiquinone
      deficiency. CoQ(10) deficiency was confirmed by decreased content of ubiquinone
      in muscle. Various missense mutations (R213W, G272V, G272D, and E551K) modifying
      highly conserved amino acids of the protein and a 1 bp frameshift insertion
      c.[1812_1813insG] were identified. The missense mutations were introduced into
      the yeast ABC1/COQ8 gene and expressed in a Saccharomyces cerevisiae strain in
      which the ABC1/COQ8 gene was deleted. All the missense mutations resulted in a
      respiratory phenotype with no or decreased growth on glycerol medium and a severe
      reduction in ubiquinone synthesis, demonstrating that these mutations alter the
      protein function.

PMID- 18319073
TI  - Using the optimal receiver operating characteristic curve to design a predictive
      genetic test, exemplified with type 2 diabetes.
AB  - Current extensive genetic research into common complex diseases, especially with
      the completion of genome-wide association studies, is bringing to light many
      novel genetic risk loci. These new discoveries, along with previously known
      genetic risk variants, offer an important opportunity for researchers to improve
      health care. We describe a method of quick evaluation of these new findings for
      potential clinical practice by designing a new predictive genetic test,
      estimating its classification accuracy, and determining the sample size required
      for the verification of this accuracy. The proposed predictive test is
      asymptotically more powerful than tests built on any other existing method and
      can be extended to scenarios where loci are linked or interact. We illustrate the
      approach for the case of type 2 diabetes. We incorporate recently discovered risk
      factors into the proposed test and find a potentially better predictive genetic
      test. The area under the receiver operating characteristic (ROC) curve (AUC) of
      the proposed test is estimated to be higher (AUC = 0.671) than for the existing
      test (AUC = 0.580).

PMID- 18319074
TI  - ADCK3, an ancestral kinase, is mutated in a form of recessive ataxia associated
      with coenzyme Q10 deficiency.
AB  - Muscle coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency has been identified in
      more than 20 patients with presumed autosomal-recessive ataxia. However,
      mutations in genes required for CoQ(10) biosynthetic pathway have been identified
      only in patients with infantile-onset multisystemic diseases or isolated
      nephropathy. Our SNP-based genome-wide scan in a large consanguineous family
      revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative
      mutation is a homozygous splice-site mutation in the aarF-domain-containing
      kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three
      patients with sporadic ataxia, including one known to have CoQ(10) deficiency in
      muscle. All of the patients have childhood-onset cerebellar ataxia with slow
      progression, and three of six have mildly elevated lactate levels. ADCK3 is a
      mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB
      proteins, which are required for CoQ biosynthesis. Three out of four patients
      tested showed a low endogenous pool of CoQ(10) in their fibroblasts or
      lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis,
      strongly suggesting that ADCK3 is also involved in CoQ(10) biosynthesis. The
      deleterious nature of the three identified missense changes was confirmed by the
      introduction of them at the corresponding positions of the yeast COQ8 gene.
      Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of
      atypical kinases, which includes phosphoinositide and choline kinases, suggesting
      that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly
      as part of a feedback loop that regulates ATP production.

PMID- 18319075
TI  - Epigenomic profiling reveals DNA-methylation changes associated with major
      psychosis.
AB  - Epigenetic misregulation is consistent with various non-Mendelian features of
      schizophrenia and bipolar disorder. To date, however, few studies have
      investigated the role of DNA methylation in major psychosis, and none have taken
      a genome-wide epigenomic approach. In this study we used CpG-island microarrays
      to identify DNA-methylation changes in the frontal cortex and germline associated
      with schizophrenia and bipolar disorder. In the frontal cortex we find evidence
      for psychosis-associated DNA-methylation differences in numerous loci, including
      several involved in glutamatergic and GABAergic neurotransmission, brain
      development, and other processes functionally linked to disease etiology. DNA
      methylation changes in a significant proportion of these loci correspond to
      reported changes of steady-state mRNA level associated with psychosis. Gene
      ontology analysis highlighted epigenetic disruption to loci involved in
      mitochondrial function, brain development, and stress response. Methylome network
      analysis uncovered decreased epigenetic modularity in both the brain and the
      germline of affected individuals, suggesting that systemic epigenetic dysfunction
      may be associated with major psychosis. We also report evidence for a strong
      correlation between DNA methylation in the MEK1 gene promoter region and lifetime
      antipsychotic use in schizophrenia patients. Finally, we observe that frontal
      cortex DNA methylation in the BDNF gene is correlated with genotype at a nearby
      nonsynonymous SNP that has been previously associated with major psychosis. Our
      data are consistent with the epigenetic theory of major psychosis and suggest
      that DNA-methylation changes are important to the etiology of schizophrenia and
      bipolar disorder.

PMID- 18319076
TI  - Characterization of apparently balanced chromosomal rearrangements from the
      developmental genome anatomy project.
AB  - Apparently balanced chromosomal rearrangements in individuals with major
      congenital anomalies represent natural experiments of gene disruption and
      dysregulation. These individuals can be studied to identify novel genes critical
      in human development and to annotate further the function of known genes.
      Identification and characterization of these genes is the goal of the
      Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort
      that leverages the recent advances resulting from the Human Genome Project to
      increase our understanding of birth defects and the process of human development.
      Clinically significant phenotypes of individuals enrolled in DGAP are varied and,
      in most cases, involve multiple organ systems. Study of these individuals'
      chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40
      chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern
      blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal
      breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and
      cryptic rearrangements were detected, but less frequently than has been reported
      previously. Chromosomal rearrangements, both balanced and unbalanced, in
      individuals with multiple congenital anomalies continue to be a valuable resource
      for gene discovery and annotation.

PMID- 18319077
TI  - Estimating ethnic admixture from pedigree data.
AB  - This paper introduces a likelihood method of estimating ethnic admixture that
      uses individuals, pedigrees, or a combination of individuals and pedigrees. For
      each founder of a pedigree, admixture proportions are calculated by conditioning
      on the pedigree-wide genotypes at all ancestry-informative markers. These
      estimates are then propagated down the pedigree to the nonfounders by a simple
      averaging process. The large-sample standard errors of the founders' proportions
      can be similarly transformed into standard errors for the admixture proportions
      of the descendants. These standard errors are smaller than the corresponding
      standard errors when each individual is treated independently. Both hard and soft
      information on a founder's ancestry can be accommodated in this scheme, which has
      been implemented in the genetic software package Mendel. The utility of the
      method is demonstrated on simulated data and a real data example involving
      Mexican families of mixed Amerindian and Spanish ancestry.

PMID- 18319078
TI  - Genetic flip-flop without an accompanying change in linkage disequilibrium.

PMID- 18319080
TI  - Optimal two-stage testing for family-based genome-wide association studies.

PMID- 18319082
TI  - In response to "Selective serotonin reuptake inhibitors--a new modality for the
      treatment of lymphoma/leukaemia?" by C. Schuster, et al. [Biochem. Pharmacol. 74
      (9) 2007 1424-1435].

PMID- 18319085
TI  - Re: Restoration of a nonrestorable central incisor using forced orthodontic
      eruption, immediate implant placement, and an all-ceramic restoration: a clinical
      report.

PMID- 18319086
TI  - Customization of milled zirconia copings for all-ceramic crowns: a clinical
      report.
AB  - Generically milled zirconia copings for all-ceramic crowns may not provide
      optimal thickness and form for the coping or the porcelain veneer. This article
      describes the customization of milled zirconia copings to provide even and
      controlled porcelain thickness with the aim of decreasing cohesive porcelain
      fracture and other failures. A full-contour waxing and cut back in conjunction
      with a dual-scan technique was used to ensure adequate coping thickness,
      adequate, even porcelain thickness, and butt joints at the porcelain-to-coping
      junctions.

PMID- 18319087
TI  - The prosthodontic rehabilitation of malpositioned implants in a patient with
      basal cell carcinoma: a clinical report.
AB  - This clinical report describes the prosthodontic rehabilitation of a patient with
      a partially edentulous maxilla and compromised mandibular anatomy caused by
      resection of bone due to basal cell carcinoma. Placement of a fibula bone graft
      was followed by placement of 2 implants. The implants were malpositioned in the
      anteroposterior plane due to the altered form of the alveolar bone. Prosthodontic
      treatment included a maxillary removable partial denture and a mandibular partial
      overdenture supported by implants and remaining teeth.

PMID- 18319088
TI  - New shade guide for tooth whitening monitoring: visual assessment.
AB  - STATEMENT OF PROBLEM: Shade guides currently used to monitor tooth bleaching lack
      logical order, uniform color distribution, and light shade tabs, thus, limiting
      the design of bleaching studies and diminishing the validity of obtained results.
      PURPOSE: The purpose of this study was to perform a visual evaluation of a new
      shade guide designed primarily for monitoring tooth whitening and to compare this
      shade guide with 2 commercial shade guides. MATERIAL AND METHODS: Tab arrangement
      of 3 shade guides (prototype of new VITA Bleachedguide 3D-Master (BG), value
      scale of Vitapan Classical (VC), and color-ordered Trubyte Bioform porcelain
      shade guide (TB)) was evaluated. The tabs from each shade guide, one at a time,
      were scattered and visually reordered from the lightest to the darkest by 15
      observers under controlled conditions of a viewing booth. Visual ranking was
      compared to manufacturer-suggested ranking. Interobserver repeatability was
      compared using the Mann-Whitney U test (alpha=.05). All observers responded to a
      questionnaire grading the 3 shade guides using a Likert scale (1, strongly
      disagree, to 5, strongly agree). The Kolmogorov-Smirnov z-test (alpha=.05) was
      used to process the results obtained in the questionnaire RESULTS: Visually
      determined BG order was found to be identical to the order given by the
      manufacturer. This was not the case with the 2 other products: visual and
      manufacturers' order were identical for 7 of 16 VC tabs and 9 of 24 TB tabs.
      Interobserver repeatability for BG was significantly higher (P<.001) as compared
      to corresponding values recorded for VC and TB, whereas no statistically
      significant difference in interobserver repeatability between VC and TB was
      observed. CONCLUSIONS: Visually determined lightest to darkest order was
      identical to the suggested manufacturer order only for VITA Bleachedguide 3D
      Master. The same shade guide was also superior based on the scores given in the
      questionnaire. These findings support the use of the new VITA Bleachedguide 3D
      Master for monitoring tooth whitening.

PMID- 18319089
TI  - Stress analysis of effects of nonrigid connectors on fixed partial dentures with
      pier abutments.
AB  - STATEMENT OF PROBLEM: In some patients, the pattern of missing teeth may require
      the use of a fixed partial denture (FPD) with an intermediate pier abutment.
      Information is needed regarding the biomechanical behavior and the position of a
      nonrigid connector for this treatment option. PURPOSE: The purpose of this study
      was to evaluate, by means of finite element method (FEM), the effects of rigid
      and nonrigid design types on stress distribution for 5-unit FPDs with pier
      abutments. MATERIAL AND METHODS: A 3-dimensional cross-section FEM model (SAP
      2000) simulating a 5-unit metal ceramic FPD with a pier abutment with rigid or
      nonrigid designs (connector location at the mesial region of the second molar, at
      the distal region of the second premolar, at the mesial region of the second
      premolar, and at the distal region of the canine) was developed. In the model,
      the canine, second premolar, and second molar served as abutments. A supporting
      periodontal ligament and alveolar bone (cortical and trabecular) were modeled. A
      50-N static vertical occlusal load was applied on the cusp of each abutment to
      calculate the stress distributions. Three different types of load were evaluated:
      loading of all cusps to simulate maximum centric occlusion contacts, loading of
      the canine to simulate a single anterior contact, and loading of the second molar
      to simulate a posterior contact. RESULTS: The analysis of the von Mises stress
      values revealed that maximum stress concentrations were located at the load areas
      for all models. Also, for all models, the highest stress values were located at
      connectors and cervical regions of abutment teeth, especially at the pier
      abutment. CONCLUSIONS: The area of maximum stress concentration at the pier
      abutment was decreased by the use of a nonrigid connector at the distal region of
      the second premolar.

PMID- 18319090
TI  - Colorimetric analysis of opaque porcelain fired to different base metal alloys
      used in metal ceramic restorations.
AB  - STATEMENT OF PROBLEM: The popularity of base metal alloys has considerably
      increased in recent years because of their superior mechanical properties as well
      as the high cost of noble alloys. However, there is disagreement about their
      effect on the opaque porcelain color and the color differences among base metal
      alloys. PURPOSE: The purpose of this in vitro study was to determine and compare
      the influence of various commercially available base metal alloys (excluding
      titanium-based systems) on the resulting color of opaque porcelain with the use
      of a colorimetric device. MATERIAL AND METHODS: Fourteen different types of Ni-Cr
      and 3 different types of Co-Cr porcelain bonding alloys were selected with a Au
      Pd alloy (V-Delta SF) as the control group for colorimetric measurements and
      determination of color shift after opaque application. Shade B1 of an opaque
      porcelain (IPS d.SIGN Opaquer) was applied (0.1 mm) to all specimens (16 mm x 1
      mm). The color coordinates of each specimen were measured with a chromameter. The
      data were displayed in L*, a*, and b* values according to the CIELAB system, and
      the color differences (DeltaE) between base metal alloys and the control group
      were calculated. Data were statistically analyzed with 1-way ANOVA (alpha=.05).
      The ANOVA was followed by Dunnett's multiple comparison test for comparisons with
      the control group to determine specifically which groups were significantly
      different from the control group. RESULTS: The L* value of only 1 base metal
      alloy was significantly different from the control group (P<.001). All base metal
      alloy groups except 3 had a* values which were significantly different from the
      control group a* value (P=.001 for Rexillium III, P=.008 for Heracles N, and
      P<.001 for the remaining 12 alloys), whereas only 3 base metal alloys were not
      statistically significantly different from the control group in the means of b*
      values (P<.001). All base metal alloys to which opaque porcelain was applied had
      significantly different DeltaE values in comparison with the control group
      (P<.001). CONCLUSIONS: The data of the study indicated that a 0.1-mm-thick layer
      of opaque porcelain applied on the Ni-Cr and Co-Cr alloys did not reliably
      reproduce the color of opaque porcelain. However, within the limitations of this
      study, the color differences of base metal alloys measured according to the
      control group are within clinically acceptable limits (DeltaE<3.5).

PMID- 18319091
TI  - The effect of repeated firings on the color of an all-ceramic system with two
      different veneering porcelain shades.
AB  - STATEMENT OF PROBLEM: Color matching between a restoration and natural teeth is a
      common clinical problem. Despite careful shade selection, color of the
      restoration may be affected by fabrication procedures. PURPOSE: The purpose of
      this study was to determine the color changes of an all-ceramic restoration with
      2 different veneering porcelain shades after repeated firings. MATERIAL AND
      METHODS: Twenty disc-shaped ceramic specimens, 4 mm in diameter with a 1-mm core
      thickness and 2 different veneering porcelain shades (A1, A3), were fabricated
      from a zirconia-based porcelain (DC-Zirkon) (n=10). Repeated firings (3, 5, 7, or
      9 firings) were performed for the specimens, and color differences (DeltaE) were
      determined using a spectrophotometer. Repeated measures ANOVA was used to analyze
      the data (number of firings, veneering porcelain color). The Tukey HSD test and
      paired 2-tailed tests were performed for multiple comparisons (alpha=.05).
      RESULTS: The L*a*b* values of the ceramic system were affected by the number of
      firings (3, 5, 7, or 9) (P<.001) and the veneering porcelain shade (P<.001).
      Significant interactions were present between the number of firings and veneering
      porcelain shade for L* (P=.003) and b* (P=.042) values, but not for the a* value
      (P=.82). An increase in the number of firings of the specimens with both A1 and
      A3 veneering porcelain shades produced an increase in the L* value, resulting in
      lighter specimens (P<.001). For both A1 and A3 veneering porcelain shades, the a*
      value decreased after repeated firings, which resulted in more green specimens
      (P=.002). The b* value did not change after repeated firings (P=.09) for the A1
      veneering porcelain shade; however, it increased for the A3 veneering porcelain
      shade, which resulted in more yellow specimens (P=.001). CONCLUSIONS: The color
      of the all-ceramic specimens with different veneering porcelain shades is
      influenced by repeated firings. However, color changes that occurred are
      clinically acceptable.

PMID- 18319092
TI  - Residual interface tensile strength of ceramic bonded to dentin after cyclic
      loading and aging.
AB  - STATEMENT OF PROBLEM: To guard against the potential risk of cusp fracture,
      esthetic onlay restorations have been advocated for teeth with large
      restorations. The influence of the adhesive resin cement is believed to play a
      role in strengthening these restorations. The durability of this
      tooth/adhesive/ceramic interface is critical to ensure clinical longevity.
      PURPOSE: The purpose of this study was to assess the effects of cyclic loading
      and environmental aging on the residual interface strength of a ceramic bonded to
      dentin structure. MATERIAL AND METHODS: Eighteen simple trilayer specimens were
      fabricated, consisting of a 1.5-mm-thick ceramic plate (ProCAD) bonded to a
      flattened human molar tooth with exposed coronal dentin. The ceramic plates were
      bonded using resin cement (Nexus 2) and manufacturer-recommended bonding
      techniques. The specimens were divided into 3 equal groups and were stored in
      water at 37 degrees C for 10 weeks as a control group (CT), 9 months as an aging
      group (AG), or placed in water at 37 degrees C while being subjected to 10
      million vertical loading cycles between 20 N to 200 N, as a fatigue group (FG).
      After the specimens were subjected to the experimental conditions, they were
      sectioned perpendicular to the flat ceramic surface into 1 x 1-mm sticks. The
      mean residual interface microtensile bond (MTB) strength was determined for each
      specimen using only those sticks which contained ceramic bonded to dentin. The
      MTB strength data were analyzed using Weibull analysis methods to determine
      differences between groups. All subsequent failed specimen surfaces were
      evaluated under a stereomicroscope at x10 magnification to determine the apparent
      failure modes. Some specimens were selected from each failure mode category for
      surface evaluation under a scanning electron microscope (SEM). RESULTS: The
      characteristic Weibull means for the 3 groups were CT, 19.2, FG, 14.7, and AG,
      11.7. The bond strength of group CT was significantly greater than both AG
      (P=.007) and FG (P=.014). Light microscopic categorization of the failure modes
      suggests that adhesive failure at the ceramic/cement interface was the most
      common (65%) for all 3 groups. SEM evaluation of failed surfaces of select
      specimens from each group could not distinguish any interface appearance
      differences. CONCLUSIONS: For indirect adhesive-retained ceramic restorations,
      both cyclic masticatory loading and hydrolytic degradation may contribute to a
      weakening of the interface bond. The ceramic/resin interface may be more
      susceptible to these changes over the time frame of this investigation than the
      dentin/resin interface.

PMID- 18319093
TI  - Ultrasound detection of submerged dental implants through soft tissue in a
      porcine model.
AB  - STATEMENT OF PROBLEM: Current methods of measuring soft tissue thickness over
      potential dental implant sites and locating submerged implants may be imprecise
      or invasive. PURPOSE: The purpose of this study was to develop and demonstrate
      proof of the concept of a customized ultrasound imaging system in locating and
      measuring the depth of implants submerged beneath soft tissue. MATERIAL AND
      METHODS: A complete ultrasound system, including a customized soft tissue-matched
      transducer, transceiver, and digital signal processing algorithms, was created
      for the specific application of detecting dental implants anchored in bone
      beneath soft tissue. The system was used to locate implants placed in cancellous
      bone and measure overlying soft tissue depth in a porcine model. Ten measurements
      were made on each porcine model by manually moving the transducer laterally over
      the soft tissue surface. Data were analyzed with descriptive statistics. RESULTS:
      The mean signal-to-noise ratio, SNR (standard deviation), from the bone surfaces,
      was 19.1 (4.6) dB, and the mean SNR from the implant surfaces was 36.6 (2.2) dB,
      resulting in a mean difference of 17.5 dB, or x56.2, in average signal power
      between the bone and implant surfaces. Consequently, implants were easily and
      accurately (+/-0.2 mm) located beneath at least 5 mm of soft tissue. Likewise,
      soft tissue depths over bone and implants were accurately measured and were
      within the corresponding caliper tissue measurement error (+/-0.5 mm).
      CONCLUSIONS: The specialized ultrasound imaging system located and measured the
      depth of implants placed in bone submerged beneath soft tissue in a porcine
      model.

PMID- 18319094
TI  - Fracture resistance of endodontically treated molars restored with extensive
      composite resin restorations.
AB  - STATEMENT OF PROBLEM: When cuspal coverage is required, there is no evidence that
      indirect composite resin restorations are superior to direct restorations in
      terms of biomechanical behavior. PURPOSE: The purpose of this in vitro study was
      to compare the fracture resistance of cusp-replacing direct and indirect
      composite resin restorations in endodontically treated molars. MATERIAL AND
      METHODS: Forty-five human mandibular molars were selected and divided into 3
      groups (n=15): DIR specimens, restored with direct composite resin (Estelite
      Sigma) restorations; IND specimens, restored with indirect composite resin
      (Estelite Sigma) restorations, and control specimens, which remained intact.
      Endodontic treatment was performed using NiTi ProTaper rotary instruments, and
      teeth were filled using lateral condensation of gutta-percha and sealer.
      Extensive Class II MO cavities were prepared, and the 2 mesial cusps were
      reduced, allowing a 2-mm layer of composite resin. All teeth were prepared to the
      same dimensions, considering reasonable human variation. Specimens were loaded to
      failure and the fracture loads were recorded (N). The mode of fracture was
      determined using a stereomicroscope and classified as favorable or unfavorable
      failure. The data were subjected to a Kruskal-Wallis test, multiple-comparison
      Mann-Whitney test, and a chi-square test (alpha=.05). RESULTS: Significant
      differences (P<.001) were observed between the control group and both DIR and IND
      groups. However, no significant difference was found between the DIR and IND
      groups. The chi-square test did not show a significant difference in the
      frequencies of favorable/unfavorable failure modes among the 3 groups (P=.981).
      CONCLUSIONS: No significant difference was observed in the fracture resistance of
      endodontically treated molars restored to original contours with an extensive
      cusp-replacing direct or indirect composite resin restoration.

PMID- 18319095
TI  - The further development and validation of the Liverpool Oral Rehabilitation
      Questionnaire (LORQ) version 3: a cross-sectional survey of patients referred to
      a dental hospital for removable prostheses replacement.
AB  - STATEMENT OF PROBLEM: The Liverpool Oral Rehabilitation Questionnaire (LORQ) is a
      health-related quality of life instrument assessing the impact of oral
      rehabilitation on patients' health-related quality of life (HRQOL) following
      treatment for oral cancer. The small number of patients wearing prostheses in
      previous studies limited the validation of the denture/denture satisfaction part
      of the questionnaire. PURPOSE: The purpose of this study was to further validate
      the LORQ by obtaining HRQOL data from patients requiring replacement dentures.
      MATERIAL AND METHODS: The LORQv3, together with items assessing mood and anxiety,
      was administered with the Oral Health Impact Profile 14-item (OHIP-14)
      questionnaire to 104 consecutive patients, between the ages of 40 and 79,
      referred by their general dentists to the department of prosthodontics at the
      Liverpool University Dental Hospital for replacement of removable prostheses
      between November 2004 and June 2005. The Mann-Whitney and Kruskal-Wallis tests
      compared scores between patient groups. Internal consistency was measured by
      Cronbach's alpha. Spearman's correlation investigated associations between items
      on the LORQv3 and items from the OHIP-14. Test-retest was measured by the kappa
      coefficient, weighted by applying standard weights according to the number of
      categories in error. RESULTS: Patients wearing complete dentures in 1 or both
      arches generally scored worse for oral function and mandibular denture
      problems/satisfaction than patients wearing removable partial dentures. Thirty
      three percent of patients were somewhat or extremely depressed, 25% were anxious
      or very anxious, and 15% were both depressed and anxious. CONCLUSIONS: The
      denture section of the LORQv3 identified expected differences among various
      patient subgroups in this cohort confirmed by similar findings for the OHIP-14
      and the literature. Thus, this part of the LORQv3 referring to dentures and
      patient satisfaction demonstrated good construct and criterion validity.

PMID- 18319096
TI  - Customizing palatal contours of a denture to improve speech intelligibility.
AB  - Accurate approximation of palatal contours of a maxillary complete denture to a
      patient's tongue can improve speech intelligibility, if other factors such as
      tooth position, occlusal plane, and occlusal vertical dimension are satisfactory.
      Customizing palatal contours of a maxillary complete denture can be accomplished
      by using tissue-conditioning material, which provides sufficient working time for
      a patient to pronounce a series of sibilant sounds while recording dynamic
      impression of the tongue. This article describes a technique for customizing
      palatal contours of a maxillary complete denture with autopolymerizing acrylic
      resin to improve speech intelligibility.

PMID- 18319097
TI  - Multiple health behavior change research: en avant, March!

PMID- 18319098
TI  - Multiple health behavior change research: an introduction and overview.
AB  - In 2002, the Society of Behavioral Medicine's special interest group on Multiple
      Health Behavior Change was formed. The group focuses on the interrelationships
      among health behaviors and interventions designed to promote change in more than
      one health behavior at a time. Growing evidence suggests the potential for
      multiple-behavior interventions to have a greater impact on public health than
      single-behavior interventions. However, there exists surprisingly little
      understanding of some very basic principles concerning multiple health behavior
      change (MHBC) research. This paper presents the rationale and need for MHBC
      research and interventions, briefly reviews the research base, and identifies
      core conceptual and methodological issues unique to this growing area. The
      prospects of MHBC for the health of individuals and populations are considerable.

PMID- 18319099
TI  - Methods of quantifying change in multiple risk factor interventions.
AB  - OBJECTIVE: Risky behaviors such as smoking, alcohol abuse, physical inactivity,
      and poor diet are detrimental to health, costly, and often co-occur. Greater
      efforts are being targeted at changing multiple risk behaviors to more
      comprehensively address the health needs of individuals and populations. With
      increased interest in multiple risk factor interventions, the field will need
      ways to conceptualize the issue of overall behavior change. METHOD: Analyzing
      data from over 8000 participants in four multibehavioral interventions, we
      present five different methods for quantifying and reporting changes in multiple
      risk behaviors. RESULTS: The methods are: (a) the traditional approach of
      reporting changes in individual risk behaviors; (b) creating a combined
      statistical index of overall behavior change, standardizing scores across
      behaviors on different metrics; (c) using a behavioral index; (d) calculating an
      overall impact factor; and (e) using overarching outcome measures such as quality
      of life, related biometrics, or cost outcomes. We discuss the methods'
      interpretations, strengths, and limitations. CONCLUSION: Given the lack of
      consensus in the field on how to examine change in multiple risk behaviors, we
      recommend researchers employ and compare multiple methods in their publications.
      A dialogue is needed to work toward developing a consensus for optimal ways of
      conceptualizing and reporting changes in multibehavioral interventions.

PMID- 18319100
TI  - Multiple Health Behavior Research represents the future of preventive medicine.
AB  - Given the disease and cost burdens, Multiple Health Behavior Research represents
      the future of preventive medicine. Growing evidence in this special issue and
      beyond indicates that simultaneous and sequential interventions can be effective.
      The challenge for the future is to make such interventions more effective, cost
      effective and less demanding. Co-variation represents one innovative approach in
      which effective change on one treated behavior increases the odds of effective
      action on a second targeted behavior. Co-variation can occur when all behaviors
      received full treatment, when one receives full treatment and the others receive
      minimal treatment and when only one behavior is treated and others co-vary
      without treatment. Integrative treatments represent another innovation in which
      higher order constructs drive change on multiple behaviors related to the
      construct and treatment has to be only on one higher order behavior. A more
      integrated approach to research and practice involves new paradigms complementing
      established paradigms. Multiple behaviors proactively treated in populations at
      home or work by computer-based and stage-based interventions designed to generate
      co-variation that produces greater impacts can complement traditional paradigms
      that treat single behaviors in individual patients in clinics by clinicians with
      action-oriented modular interventions designed for specific behaviors to produce
      significant efficacy. More inclusive research to support more inclusive practices
      can hopefully lead to more inclusive care.

PMID- 18319101
TI  - The diagnosis and management of cardiovascular disease in cancer patients.
      Foreword.

PMID- 18319102
TI  - The diagnosis and management of cardiovascular disease in cancer patients.
AB  - Cardiovascular disease is commonly found in cancer patients. The co-existence of
      heart disease and cancer in a patient often complicates treatment, because
      therapy for one disease may negatively affect the outcome of the other disease.
      In addition, guidelines for the treatment of cardiovascular disease are often
      based on studies, which exclude patients who have cancer. In this review we will
      discuss the diagnosis and management of cardiovascular disease in cancer
      patients. We will focus on cancer-related causes of cardiovascular disease and
      special treatment options for cardiovascular disease in cancer patients. The
      cardiac complications of cancer therapy will be discussed according to common
      syndromes: left ventricular dysfunction, myocardial ischemia, blood pressure
      changes, thromboembolism, bradyarrhythmias, and prolonged QT interval.

PMID- 18319103
TI  - Statistical tools in the quest for truth: hypothesis testing, confidence
      intervals, and the power of clinical studies.

PMID- 18319104
TI  - Keratoprosthesis surgery for end-stage corneal blindness in asian eyes.
AB  - PURPOSE: To establish a multidisciplinary surgical program for osteo-odonto
      keratoprosthesis (OOKP) surgery in Asia and to evaluate efficacy and preliminary
      safety of this keratoprosthesis in end-stage corneal and ocular surface disease.
      DESIGN: Prospective noncomparative case series. PARTICIPANTS: Sixteen adults of
      Asian ethnic origin, bilaterally blind with end-stage corneal blindness from
      Stevens-Johnson syndrome, or severe chemical or thermal burns. METHODS: Osteo
      odonto-keratoprosthesis surgery involves 2 procedures-in stage 1, an autologous
      canine tooth is removed, modified to receive an optical polymethyl methacrylate
      cylinder, and implanted into the cheek. The ocular surface is denuded and
      replaced with full-thickness buccal mucosa. Stage 2 surgery, performed 2 to 4
      months later, involves retrieval of the tooth-cylinder complex and implanting it
      into the cornea, after reflection of the buccal mucosal flap, corneal
      trephination, iris and lens removal, and anterior vitrectomy. Concurrent glaucoma
      and vitreoretinal procedures are also performed at either stage, as required.
      MAIN OUTCOME MEASURES: Visual acuity (VA), field of vision, anatomical integrity
      and stability, and ocular and oral complications related or unrelated to the OOKP
      device. RESULTS: Osteo-odonto-keratoprosthesis surgery was performed on 15
      patients, with a mean follow-up of 19.1 months (range, 5-31). Intraoperative
      complications included expulsive hemorrhage (keratoprosthesis device not
      implanted), tooth fracture (n = 1), oronasal fistula (n = 1), and mild inferior
      optic tilt (n = 1). Anatomical stability and keratoprosthesis retention has been
      maintained in all eyes, with no dislocation, extrusion, retroprosthetic membrane
      formation, or keratoprosthesis-related infection. Other complications not
      directly related to device insertion included retinal detachment (RD) related to
      silicone oil removal (n = 1) and endophthalmitis related to endoscopic
      cyclophotocoagulation performed 1 year after OOKP surgery (n = 1). Eleven
      patients (73.3%) attained a stable best spectacle-corrected VA of at least 20/40
      or better, whereas 9 (60%) attained stable 20/20 vision. Four patients achieved
      their best visual potential, ranging from 20/100 to counting fingers vision,
      related to preexisting glaucomatous optic neuropathy or previous RD. CONCLUSIONS:
      Establishment of our OOKP program suggests that OOKP surgery has the potential to
      restore good vision to the most severe cases of corneal blindness in an Asian
      setting, with minimal device-related complications. Longer follow-up of these
      cases is currently underway.

PMID- 18319105
TI  - Guidelines for PDT in Japan.

PMID- 18319106
TI  - Bevacizumab and macular edema.

PMID- 18319107
TI  - Timing of detachment surgery.

PMID- 18319110
TI  - Posterior corneal surface.

PMID- 18319111
TI  - Corneal magnification.

PMID- 18319112
TI  - OCT of corneal opacities.

PMID- 18319115
TI  - Normal-tension glaucoma.

PMID- 18319117
TI  - Phakic IOLs in Children.

PMID- 18319119
TI  - Infantile orbital cellulitis.

PMID- 18319121
TI  - Glass ceiling?

PMID- 18319122
TI  - Patient safety in obstetrics and gynecology: improving outcomes, reducing risks.
      Foreword.

PMID- 18319123
TI  - Patient safety in obstetrics and gynecology: improving outcomes, reducing risks.
      Preface.

PMID- 18319124
TI  - Scope of problem and history of patient safety.
AB  - Creating a safe environment in our incredibly complex health care system requires
      a major culture change. While it may be frustratingly slow and halting, that
      change is occurring and beginning to show results. This article addresses the
      issue of patient safety, discussing its history, and organizations and practices
      that are helping to make it more of a reality in today's health care environment.

PMID- 18319125
TI  - Medical error theory.
AB  - Some errors in health care are inevitable because of human fallibility and system
      complexity. To improve patient safety we must develop three strategies. First,
      prevent errors with forcing functions, reducing complexity and providing
      reminders at the point of care. Second, everyone working in health care should be
      alert to identify and eliminate latent (potential) errors before patients are
      harmed. Finally, we must establish defensive barriers that will intercept those
      errors that still occur and prevent them from causing patient injury. Only in
      this way can health care fulfill its potential and significantly reduce
      iatrogenic harm.

PMID- 18319126
TI  - Practical solutions to improve safety in the obstetrics/gynecology office setting
      and in the operating room.
AB  - There are great opportunities to enhance patient safety in office practice, but
      the pattern of medical errors and techniques to reduce their frequency appears to
      differ from the hospital environment. A focus on decreasing the risks of
      prescribing errors and tracking errors may be particularly fruitful in the office
      setting, such as electronic prescribing, electronic medical records, the use of
      detailed patient instructions, unambiguous prescribing, and meticulous follow-up
      of test results. The surgical environment presents its own unique set of risks to
      patient safety, particularly because of the catastrophic consequences that may
      result from even infrequent events. Vigilance against stress and fatigue is
      particularly important. Patient safety in surgery is promoted by routine use of
      the "universal protocol," antibiotic prophylaxis, thromboprophylaxis, open
      communication among all members of the surgical team, and clear guidelines for
      introducing new procedures and technology.

PMID- 18319127
TI  - Medication safety.
AB  - Patient safety is a state of mind, not a technology. The technologies used in the
      medical setting represent tools that must be properly designed, used well, and
      assessed on an on-going basis. Moreover, in all settings, building a culture of
      safety is pivotal for improving safety, and many nontechnologic approaches, such
      as medication reconciliation and teaching patients about their medications, are
      also essential. This article addresses the topic of medication safety and
      examines specific strategies being used to decrease the incidence of medication
      errors across various clinical settings.

PMID- 18319128
TI  - Transparency, apology and disclosure of adverse outcomes.
AB  - Medical errors became a common topic of conversation with the release of the
      Institute of Medicine's "To Err Is Human" in November of 1999. This release
      reported that as many as 98,000 people die each year from inpatient medical
      errors. Putting this into perspective, deaths from medical errors surpassed
      deaths from breast cancer, motor vehicle accidents, and AIDS. Furthermore,
      medication errors account for more deaths annually than workplace injuries. This
      article addresses communication of adverse outcomes to patients (disclosure)
      through transparency and apology.

PMID- 18319129
TI  - Electronic health records and electronic prescribing: promise and pitfalls.
AB  - Health information technology (health IT), especially technology related to
      electronic health records (EHRs) and electronic prescription (e-prescribing)
      systems, is believed to be the cornerstone for improvements in quality of care,
      patient safety, and efficiencies, all leading to cost benefits. With increasing
      requirements for quality reporting and with new pay-for-performance programs
      being initiated by insurers, many physicians are asking if it is time to invest
      in health IT. However, as those who have already made this decision have found,
      adopting EHRs and e-prescribing systems is not an easy task: Our colleagues
      resist their use, they are costly, the case for a return on investment for an
      ambulatory practice has not been well established, incentives to use are
      misaligned, implementations may be difficult, and often such systems disrupt or
      inhibit workflow.

PMID- 18319130
TI  - Team function in obstetrics to reduce errors and improve outcomes.
AB  - Crew resource management (CRM), adapted from aviation for the practice of
      medicine, offers the potential of reducing medical errors, increasing employee
      retention, and improving patient satisfaction. CRM, however, requires a culture
      that promotes teamwork and acceptance of new concepts. Leadership is needed to
      transform the culture, as well as to train, coach, and sustain the behavior CRM
      demands. Culture change can be fostered through teamwork activities that, when
      made part of a daily routine, provides the basis for modeling teamwork skills and
      sets the stage for sustained culture change. New tools are available to measure
      processes as well as patient and staff satisfaction.

PMID- 18319131
TI  - Simulation in obstetrics and gynecology.
AB  - Simulation is a practical and safe approach to the acquisition and maintenance of
      task-oriented and behavioral skills across the spectrum of medical specialties,
      including obstetrics and gynecology. Since the 1990s, the profession of
      obstetrics and gynecology has come to appreciate the value of simulation and
      major steps are being taken toward incorporating this technique into specialty
      specific training, evaluation, and credentialing programs. This article provides
      an overview of simulators and simulation in health care and describes the scope
      of their current use and anticipated applications in the field of obstetrics and
      gynecology.

PMID- 18319132
TI  - Elements of a successful quality improvement and patient safety program in
      obstetrics and gynecology.
AB  - In this article we present the elements of one approach to quality improvement
      and patient safety that we believe can be successful and sustainable in the field
      of obstetrics and gynecology, along with several strategies (and caveats) that
      have worked and are working in academic and nonacademic institutions in the
      United States. Also included are several noteworthy definitions of quality to
      provide some additional perspectives on what is meant by quality in health care.

PMID- 18319133
TI  - Quality assessment tools: ACOG Voluntary Review of Quality of Care Program, Peer
      Review Reporting System.
AB  - The Voluntary Review of Quality of Care Program is the American College of
      Obstetricians and Gynecologists' program of peer review. It is dedicated to
      quality improvement, patient safety, and peer review, which is conducted by a
      national professional specialty organization. Since the program's inception, 236
      hospitals providing obstetric and gynecologic services in this country have been
      reviewed. This article presents the results of these reviews. Common problems are
      identified and possible corrective action is recommended. This program represents
      a useful model of national peer review activity that can impact patient care.

PMID- 18319134
TI  - An environmental approach to correcting iodine deficiency: supplementing iodine
      in soil by iodination of irrigation water in remote areas.
AB  - OBJECTIVE: Iodine deficiency disorders continue to be a severe problem in many
      parts of Central Asia, causing delayed mental development and cretinism in
      indigenous populations. In some areas, iodized salt has not succeeded in
      controlling this problem. In southern Xinjiang Province of China, we tried a new
      method of supplying iodine to rural populations by dripping potassium iodate into
      irrigation water canals. By this means iodine was distributed into soil, crops,
      animals and people. This proved feasible and cost effective; it reached all the
      people, required no medical expertise, required no continuing effort after the
      initial dripping, and had the important added benefit of improving livestock
      production. METHODS: We serially monitored iodine concentrations in soil, crops,
      animal products and human urine for several years after the last dripping. In a
      similar project in Inner Mongolia, total soil iodine was determined in addition.
      Here, iodine concentrations in soil, crops, animals and people have been
      monitored for 4 years after supplementation. RESULTS: After dripping, total
      iodine increased two-fold, while soluble iodine increased 4-5-fold. Iodine added
      to soil is available for more than 4 years after a single application.
      CONCLUSIONS: Potassium iodate added to soil appears to increase soluble iodine
      out of proportion to the amount added. This effect and the long persistence of
      dripped iodate in soil contribute to the efficacy and cost effectiveness of this
      method of iodine supplementation.

PMID- 18319135
TI  - Effects of selenium status and supplementary seleno-chemical sources on mouse T
      cell mitogenesis.
AB  - Although selenium is thought to be essential for various immune responses, the
      excess supplementation may have an adverse effect on certain immunological
      functions. The present study was designed to determine the effective chemical
      forms of selenium and their optimal levels on T-cell mitogenesis with splenic
      cells from mice given a selenium-deficient diet for 8 weeks to avoid effects of
      cellular selenium sources. Although selenium in tissues, except for spleen and
      thymus, was almost depleted by feeding selenium-deficient diet, the lymphoid
      organs still contained low levels of selenium. Both activities of cellular
      glutathione peroxidase (cGPx) and thioredoxin reductase (TR) in liver and splenic
      cells showed a tendency to decrease by selenium deficiency. However, splenic
      cells were tolerant against decrease of the selenoenzyme activities, and TR was
      also more tolerant than cGPx. T-cell proliferation of the selenium-insufficient
      splenic cells induced by concanavalin A was increased by addition of Na2SeO3,
      Na2SeO4, Na2Se, seleno-DL-cystine, seleno-L-methionine and selenocystamine. Their
      promoting action was observed at levels lower than 0.1 micromol/L and was
      completely suppressed at the highest concentration (1 micromol/L), except for
      selenocystamine. Na2SeO3 was one of the efficient selenocompounds for the
      mitogenesis, which was concomitant with the significant induction of cGPx and TR.
      However, recovery of cGPx activity in the selenium-insufficient cells by
      supplementary Na2SeO3 was only partial,while TR activity was readily recovered
      from selenium deficiency. These results therefore indicate that only low levels
      of selenium is essential for T-cell mitogenesis even in selenium-insufficient
      splenic cells, and TR, which is readily recovered by Na2SeO3, may be the critical
      enzyme.

PMID- 18319136
TI  - Element distribution is altered in a zone surrounding human glioblastoma
      multiforme.
AB  - Recent data indicate that A(1) adenosine receptor (A(1)AR) density is increased
      in a zone surrounding human and experimental gliomas. On the contrary, tumor
      tissue and adjacent brain tissue show low to intermediate A(1)AR densities. In
      order to assess whether changes in A(1)AR expression are indicating further
      processes of a chemical reorganization of the peritumoral zone, we investigated
      element concentrations and distribution patterns of copper and zinc in six human
      glioblastoma multiforme (GBM) specimens by laser ablation-inductively coupled
      plasma-mass spectrometry (LA-ICP-MS). Uranium and lead were used as external
      standards. Copper and zinc levels were increased in a peritumoral zone
      corresponding to the region of elevated A(1)AR density. They showed a lower
      density in the solid tumor in comparison to surrounding brain tissue, although
      the cellular density was higher within GBM. Our findings suggest that the
      immediate vicinity of GBM is characterized by increased levels of copper and zinc
      supporting the view that higher A(1)AR density surrounding GBM is not an isolated
      alteration of peritumoral tissue but an indicator of complex changes in the
      vicinity of infiltrative tumors. Further research is needed to explore the
      pathophysiological consequences of altered peritumoral element distribution.

PMID- 18319137
TI  - New assay for the measurement of selenoprotein P as a sepsis biomarker from
      serum.
AB  - Selenium (Se) is incorporated into selenoproteins as the 21st proteinogenic amino
      acid selenocysteine. Serum Se concentrations decline during critical illness and
      are indicative of poor prognosis. Serum Se is mainly contained in the hepatically
      derived selenoprotein P (SePP) which controls the expression of antioxidative
      selenoproteins. Here, we describe the development of an immunoluminometric
      sandwich assay that uses two polyclonal sheep antihuman SePP antibodies. After
      assessing the stability of the analyte, we determined SePP concentrations in
      samples from healthy individuals and patients with sepsis. The analytical
      detection limit was 0.016 mg SePP/L serum. The assay was linear on dilution. SePP
      was stable in serum at room temperature for at least 24 h and resistant to six
      freeze-thaw cycles. Median SePP concentration in healthy individuals was 3.04 mg
      SePP/L serum (25th-75th percentiles, 2.6-3.4 mg/L) which corresponded to 98.4
      microg Se/L serum. The interlaboratory CV was <20% for SePP values >0.06 mg/L.
      There was no association with gender, but concentrations differed between young
      and older individuals. Median SePP concentrations were significantly (P<0.0001)
      decreased in patients with sepsis (n=60) compared to healthy controls (n=318).
      Since SePP contains the major fraction of serum Se, we conclude that
      downregulation of SePP biosynthesis or removal of circulating SePP from blood
      underlies the negative acute phase response of serum Se in critical illness.

PMID- 18319138
TI  - Effect of high dietary copper on weight gain and neuropeptide Y level in the
      hypothalamus of pigs.
AB  - An experiment was performed to examine the effect of dietary copper
      supplementation on weight gain, neuropeptide Y (NPY) concentration and NPY mRNA
      expression level in the hypothalamus of pigs. Forty-five crossbred pigs were
      randomly assigned to three groups of 15 pigs, each comprising five replicates of
      3 animals. Pigs were allocated to diets that contained 10mg/kg (as a control),
      125 and 250 mg/kg copper as CuSO4. Live weight gain and feed conversion
      efficiency was determined at the end of the experiment and five pigs, selected at
      random from each group, were slaughtered and the hypothalami collected for
      determination of NPY concentration and NPY mRNA expression level. The results
      showed that average daily gain (ADG) and average daily feed intake (ADFI) were
      higher and feed:gain (F:G) ratio was lower in pigs fed the diets with 125 and 250
      mg/kg copper (P<0.05), respectively, than in pigs fed a diet with 10 mg/kg
      copper, but that there was no statistically significant difference in growth
      performance between animals of the 125 mg/kg and the 250 mg/kg copper groups.
      Furthermore, pigs fed diets with 125 and 250 mg/kg copper had higher NPY
      concentrations and NPY mRNA expression levels in their hypothalamus than control
      animals. The data indicated that 125 and 250 mg/kg copper gave similar responses
      in terms of weight gain, whilst high dietary copper could enhance NPY
      concentration and NPY mRNA expression level in the hypothalamus of pigs. High
      dietary copper appears to increase feed intake and promote weight gain by
      enhancing NPY concentration and NPY mRNA expression level in the hypothalamus of
      pigs.

PMID- 18319139
TI  - A novel silicon complex is as effective as sodium metasilicate in enhancing the
      collagen-induced inflammatory response of silicon-deprived rats.
AB  - An experiment was conducted with rats to determine whether silicon deprivation
      affects the inflammatory response to the injection of type II collagen, and to
      compare the effectiveness of the organic complex arginine silicate inositol (ASI)
      with inorganic silicon (NaSiO(3)) in mitigating any observed change in response.
      Dark Agouti rats were fed a ground corn-casein-safflower-based diet containing
      about 2.8 mg Si/kg. The experimental variables were supplemental 0 and 35 mg
      Si/kg as either ASI or NaSiO3. After five weeks on their respective treatments,
      each rat was injected with type II collagen and euthanized four weeks later.
      Urine was collected before injection during week five and week nine before
      euthanasia. The silicon-supplemented rats generally exhibited a more marked
      inflammatory response than the silicon-deprived rats. The circulating number of
      lymphocytes was higher (p<0.003) and number of neutrophils was lower (p<0.008) in
      silicon-deprived than silicon-supplemented rats. ASI and NaSiO3 were about
      equally effective in enhancing these changes. Post-injection of tibial release of
      prostaglandin E(2) (PGE(2)) (p<0.04), urinary excretion of magnesium (p<0.03) and
      deoxypyridinoline (p<0.009), and plasma osteopontin (p<0.009), magnesium
      (p<0.0007) and copper (p<0.004) were higher in silicon-supplemented than silicon
      deprived rats. The increases in plasma magnesium (Si x sex, p<0.04) and copper
      (Si x sex, p<0.02) were more marked in male than female rats. One but not the
      other silicon supplement when compared to silicon deprivation significantly
      affected the tibial release of PGE(2), and plasma copper and iron concentrations.
      However, with the exception of the pre-injection urinary excretion of helical
      peptide, no other of the variables determined was significantly different between
      rats fed ASI and those fed NaSiO3. The findings suggest that, in rodents,
      physiological amounts of silicon promote the immune response, sex may influence
      the response to dietary silicon, and that both organic silicon complexes and
      inorganic silicon are similarly effective in preventing changes in inflammation
      induced by silicon deprivation.

PMID- 18319140
TI  - Non-ceruloplasmin-bound copper in routine clinical practice in different
      laboratories.
AB  - BACKGROUND: Copper is an essential nutrient but is toxic when the free form is in
      excess. Wilson's disease (WD) is an autosomal recessive disorder of copper
      excess. Its diagnosis is a challenge, especially in the absence of obvious
      neurological changes, or Kayser-Fleischer rings. Non-ceruloplasmin-bound copper
      is a calculated parameter devised for the investigation of patients who
      potentially have WD. METHODS: We compared non-ceruloplasmin-bound copper from
      three different laboratories. We retrospectively reviewed paired ceruloplasmin
      and copper data and calculated non-ceruloplasmin-bound copper. Comparative
      statistics, linear regression, chi-square test and graphical techniques were
      employed to compare the data. RESULTS: All three assays had negative results for
      over 20% of the non-ceruloplasmin-bound copper concentrations; this was not
      significantly different. However, there were statistically significant
      differences for the 97.5th percentile. When plotted against the ceruloplasmin and
      copper concentrations, significant differences existed for both the visual and
      linear regression data between the three different laboratories. CONCLUSIONS: Non
      ceruloplasmin-bound copper cut-offs may not be transferable between laboratories.
      Each laboratory should derive its own cut-offs for the 97.5th percentile, as
      there are differences due to assays, populations or both.

PMID- 18319141
TI  - Selenium in placenta predicts birth weight in normal but not intrauterine growth
      restriction pregnancy.
AB  - Placental selenium, lead and cadmium concentrations were determined in a group of
      pregnancies with birth weight appropriate for gestational age and in a group of
      intrauterine growth restriction cases. Following adjustment for a number of
      confounding variables, selenium was found to be a significant predictor of
      newborn weight only in the group of pregnancies with birth weights appropriate
      for gestational age. Placental lead and cadmium levels were not associated with
      birth weight in either group.

PMID- 18319142
TI  - Acute effects on the lung and the liver of oral administration of cerium chloride
      on adult, neonatal and fetal mice.
AB  - We evaluated tissue changes associated with cerium chloride administration via
      gavage to adult mice, via milk to neonatal mice and transplacentally to fetal
      mice. Change in adults consisted of extensive pulmonary hemorrhage, pulmonary
      venous congestion, thickened alveolar septae, hepatic necrosis and neutrophil
      infiltrations. Those in fetal mice consisted of pulmonary and hepatic congestion.
      These results indicate that gavage cerium administration elicited subtle tissue
      changes, though oral toxicity is rather low. These changes were less severe in
      neonatal and fetal mice. When cerium was injected into adult mice through the
      tail vein, cerium was distributed mainly to the liver, spleen and lung dose
      dependently with the cerium concentration gradually decreasing after 3 days. A
      study of cerium anticoagulation in mouse plasma showed that clotting time was
      significantly prolonged when cerium was added to plasma. These results suggest
      that cerium may disturb blood coagulation and cause pulmonary and hepatic
      vascular congestion.

PMID- 18319143
TI  - Relation between lipid peroxidation and iron concentration in mouse liver after
      acute and subacute cadmium intoxication.
AB  - In this study the effect of acute and subacute cadmium (Cd) intoxication on iron
      (Fe) concentration and lipid peroxidation (LPO) was investigated in the livers of
      Swiss mice. Animals were divided into two groups: the Cd group--mice intoxicated
      with Cd and controls. In acute time-response studies, Fe and malondialdehyde
      (MDA) levels were determined at 4, 6, 12, 24 and 48 h after a single oral dose of
      Cd (20 mg Cd/kg b.w.). In the subacute experiment, mice were given 10 mg Cd/kg
      b.w. orally every day for 14 days; Fe and MDA contents were determined in liver
      after 1 and 2 weeks. Acute Cd intoxication induced a significantly increased
      hepatic Fe content after 4 and 6h, and a statistically significant increase in
      MDA 6, 12 and 24h after Cd administration, although a significantly decreased MDA
      level was observed after 48 h. The results suggest development of early oxidative
      stress in livers of mice after acute intoxication with Cd. The decreased MDA
      observed after 48 h occurred presumably due to the adaptive response of the
      organism. Subacute Cd intoxication induced a significant decrease of hepatic Fe
      and MDA levels at both investigated time intervals compared with control. These
      results indicate a positive correlation between hepatic Fe and MDA content and
      suggest that prolonged Cd intoxication decreases hepatic LPO indirectly, by
      reducing the Fe content of mouse liver.

PMID- 18319144
TI  - Paradigm shifts in fungal secondary metabolite research.
AB  - The 8th International Mycological Congress (IMC8; Cairns, Australia) hosted
      several plenary lectures, poster presentations, and even entire symposia
      dedicated to fungal secondary metabolites (extrolites). These advances, presented
      in this special issue, together demonstrated how the impact of molecular biology
      and genomics and the availability of sophisticated methods of analytical
      chemistry has resulted in paradigm shifts in our understanding of fungal
      secondary metabolism and its key role in fungal biology. Rather than focus on
      classical topics such as discovery of novel drug candidates and identification of
      toxins, here we address two major themes in this special issue: (1) the utility
      and importance of secondary metabolites and their genes in polyphasic taxonomy,
      phylogeny, and evolutionary history of kingdom Fungi (syn. Eumycota); and (2) the
      genetic processes regulating secondary metabolite biosynthesis. The history of
      fungal chemotaxonomy and some important classes of secondary metabolites are
      reviewed.

PMID- 18319145
TI  - The use of secondary metabolite profiling in chemotaxonomy of filamentous fungi.
AB  - A secondary metabolite is a chemical compound produced by a limited number of
      fungal species in a genus, an order, or even phylum. A profile of secondary
      metabolites consists of all the different compounds a fungus can produce on a
      given substratum and includes toxins, antibiotics and other outward-directed
      compounds. Chemotaxonomy is traditionally restricted to comprise fatty acids,
      proteins, carbohydrates, or secondary metabolites, but has sometimes been defined
      so broadly that it also includes DNA sequences. It is not yet possible to use
      secondary metabolites in phylogeny, because of the inconsistent distribution
      throughout the fungal kingdom. However, this is the very quality that makes
      secondary metabolites so useful in classification and identification. Four groups
      of organisms are particularly good producers of secondary metabolites: plants,
      fungi, lichen fungi, and actinomycetes, whereas yeasts, protozoa, and animals are
      less efficient producers. Therefore, secondary metabolites have mostly been used
      in plant and fungal taxonomy, whereas chemotaxonomy has been neglected in
      bacteriology. Lichen chemotaxonomy has been based on few biosynthetic families
      (chemosyndromes), whereas filamentous fungi have been analysed for a wide array
      of terpenes, polyketides, non-ribosomal peptides, and combinations of these.
      Fungal chemotaxonomy based on secondary metabolites has been used successfully in
      large ascomycete genera such as Alternaria, Aspergillus, Fusarium, Hypoxylon,
      Penicillium, Stachybotrys, Xylaria and in few basidiomycete genera, but not in
      Zygomycota and Chytridiomycota.

PMID- 18319146
TI  - Affinities of Phylacia and the daldinoid Xylariaceae, inferred from chemotypes of
      cultures and ribosomal DNA sequences.
AB  - A chemotaxonomic evaluation using hplc profiling was undertaken to resolve the
      infrageneric and intergeneric affinities of over 150 strains of Xylariaceae.
      Daldinia placentiformis, Hypoxylon nicaraguense, H. polyporus, and Phylacia
      sagrana were found to contain 8-methoxy-1-naphthol, which is apparently absent in
      Annulohypoxylon, Hypoxylon, and related genera with bipartite stromata. D.
      placentiformis and other species of Daldinia and Entonaema produced this
      naphthol, 5-hydroxy-2-methylchromone, isosclerone derivatives, and 'AB-5046'
      phytotoxins. Phylacia sagrana differed from most Daldinia spp., except for D.
      caldariorum, by producing eutypine derivatives in addition to the above
      compounds. Indolylquinones were observed in H. nicaraguense and H. polyporus.
      Isosclerones were also identified in the A. multiforme complex, but Hypoxylon and
      other Annulohypoxylon and most Hypoxylon spp. studied Annulohypoxylon spp.
      contained 5-methylmellein as the major metabolite of their cultures. Based on the
      occurrence of the above metabolites, further mellein-type dihydroisocoumarins,
      teleomorphic and anamorphic Xylariaceae with Nodulisporium-like anamorphs
      ('Hypoxyloideae') were divided into various chemotypes. A comparison of their
      5.8S/ITS nuc-rDNA sequences agreed in some important aspects with the above
      results: H. nicaraguense and H. polyporus appeared basal to a clade comprising
      Daldinia, Entonaema, and Ph. sagrana. The latter species appeared allied to D.
      caldariorum, but was distantly related to Pyrenomyxa morganii and Hypoxylon s.
      str.

PMID- 18319147
TI  - Predicting the use of individualized risk assessment for breast cancer.
AB  - PURPOSE: The purpose of this study was to investigate the decision to obtain
      individualized risk assessment (IRA) after a breast cancer education session.
      METHODS: A sample of both African American and Caucasian women was used to
      determine if there were differences by race/ethnicity in uptake of the assessment
      and differences in the variables that were most predictive of uptake. The sample
      included 166 women between the ages of 18 and 80. Sixty-two percent of the sample
      were African American women. KEY FINDINGS: The results suggested that African
      American women and Caucasian women used different factors and used other factors
      differently to decide whether or not to obtain an IRA. CONCLUSIONS AND
      IMPLICATIONS: These results are discussed within the context of health
      disparities among ethnic minority and Caucasian women with implications for
      breast cancer control programs. The results of this study suggest that knowledge
      alone does not lead to opting for a personalized risk assessment, and that
      African American and Caucasian women use different pieces of information, or
      information differently to make decision about getting more personalized
      information about risk.

PMID- 18319148
TI  - Quality control in a National Program for the Early Detection of Breast Cancer:
      women's satisfaction with the mammography process.
AB  - INTRODUCTION: The experience of the mammography testing process and related
      satisfaction influence women's willingness to undergo the test again. The study
      goal was to assess women's overall satisfaction with the mammography examination
      service provided by participating units in the National Program for the Early
      Detection of Breast Cancer in Israel. METHODS: Between August 2003 and March
      2004, a random sample of 3,295 women from 38 mammography units nationwide was
      drawn. Women were interviewed within 48 hours of their mammography, regarding
      their assessment of the examination process: discomfort, overall satisfaction,
      and intention to rescreen. Overall satisfaction and process items were measured
      on an ordinal scale ranging from 1 (lowest) to 6 (highest). Multivariate binomial
      regression was performed to identify significant predictors of being less
      satisfied and to estimate the associated relative risks with 95% confidence
      interval (CI). RESULTS: A response of "very satisfied" (score 6), indicating
      overall satisfaction with the mammography process, was reported by 77% (95% CI,
      73%-80%) of the women, 19% (95% CI, 17%-21%) said they were satisfied.
      Willingness to rescreen was reported by 95%. Negative assessment of staff
      attitude was the most influential predictor of being less satisfied. Twenty-six
      percent of women reported experiencing very discomforting pain. This response was
      associated with a diagnostic test indication, and with process items directly
      related to the test (technician's attitude toward the patient; information
      provided by her; privacy during the test). CONCLUSIONS: Women's satisfaction was
      high, as was intention to rescreen. The gap between intention and rescreening
      begs further investigations as to other types of barriers preventing women from
      adherence to rescreening.

PMID- 18319149
TI  - Physical and sexual violence among North Carolina women: associations with
      physical health, mental health, and functional impairment.
AB  - OBJECTIVE: This study examines links between women's experiences of violence
      during adulthood (including physical and sexual violence) and women's physical
      health, mental health, and functional status. METHODS: Data were analyzed from a
      representative sample of 9,830 North Carolina women surveyed by the North
      Carolina Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: One-quarter
      of the women experienced violence as adults, with current or ex-partners being
      the most common perpetrators. Logistic regression analyses that controlled for
      the sociodemographic characteristics of the women found that women who
      experienced violence were significantly more likely than other women to have poor
      physical health, poor mental health, and functional limitations. Moreover, these
      negative health outcomes were most prevalent among the women who experienced a
      combination of both physical and sexual violence. CONCLUSIONS: These findings
      underscore the need for trauma-informed women's health services and policies.

PMID- 18319150
TI  - Viruses and prion in the CNS. Foreword.

PMID- 18319151
TI  - Viruses and prion in the CNS. Preface.

PMID- 18319152
TI  - CNS viruses--diagnostic approach.
AB  - Diagnosis of CNS viral infections is challenging; yet, significant progress in
      laboratory diagnosis of CNS infections has come through applications of serology
      and polymerase chain reaction (PCR) to CSF and tissues. Advances in molecular and
      laboratory techniques, together with neuroimaging, epidemiologic, and
      surveillance efforts, are yielding greater success in CNS viral diagnosis and
      treatment.

PMID- 18319153
TI  - Neuropathology of viral infections of the central nervous system.
AB  - Many viral infections of the nervous system cause stereotyped pathologic features
      and overlapping clinical and imaging features. Neuroimaging usually offers
      neuroanatomical localization of the pathology, degree of involvement of the
      nervous system, and response to therapy during follow up in a few instances.
      Neuroimaging is a useful adjunct for diagnosis.

PMID- 18319154
TI  - Imaging of nonspecific (nonherpetic) acute viral infections.
AB  - Encephalitis is an acute infection of brain parenchyma characterized clinically
      by fever, headache, and an altered level of consciousness. In the twenty-first
      century several outbreaks of encephalitis have been reported. Urbanization and
      encroachment on natural environments, the ease of world travel, and global trade
      have led to the spread of vectors and viruses.

PMID- 18319155
TI  - Central nervous system infections of herpesvirus family.
AB  - Herpesviruses are one of the most common groups of pathogens causing central
      nervous system infections in humans. They mostly cause encephalitis, meningitis,
      or myelitis in immunocompetent and immunocompromised patients. Children, adults,
      and the elderly can all be affected. Although contrast-enhanced CT is more widely
      used for diagnosis, contrast-enhanced MR imaging combined with diffusion-weighted
      imaging is superior to CT in the detection of early changes and the real extent
      of the disease, and in assessing prognosis and monitoring response to antiviral
      treatment. More sophisticated techniques, such as MR spectroscopy and perfusion
      imaging, can aid in the differential diagnosis of herpesvirus infections from
      other tumoral, demyelinating, and ischemic processes.

PMID- 18319156
TI  - Imaging of topographic viral CNS infections.
AB  - Infections caused by enteroviruses, rabies, adenoviruses, and Nipah and Hanta
      viruses are discussed. Several studies defined the pattern of MR imaging findings
      in these disease processes that reflect parenchymal infiltration with
      inflammatory cells, typically visualized as areas of low attenuation on CT, as
      well as of low T1 and high T2 signal intensity on MR imaging. Diffusion-weighted
      MR imaging has been shown to be superior to conventional magnetic resonance
      imaging for the detection of early signal abnormalities in encephalitis. Focal
      unilateral hyperperfusion as visualized by SPECT appears to be an indicator of
      severe inflammation of the brain tissue and was found to be an independent
      predictor of poor prognosis, whereas clinical outcome variables, CSF, or EEG
      findings are not.

PMID- 18319157
TI  - Neuroimaging in the brain in HIV-1-infected patients.
AB  - The brain may be affected by a variety of abnormalities in association with HIV
      infection. Knowledge of these abnormalities and their characteristic imaging
      features is important to neuroradiologists for the detection, diagnosis, and
      initiation of appropriate treatment. This review attempts to describe the imaging
      findings associated with brain disorders in HIV-seropositive patients and the
      rationales for integrating neuroradiologic techniques.

PMID- 18319158
TI  - Neuroimaging of viral infections in infants and young children.
AB  - Many viral infections can involve the central nervous systems (CNS) of fetuses,
      neonates, infants, and children. The pathogenesis, patterns of CNS involvement,
      and species of viral infection may differ in the developing fetus, infant and
      neonate, and early childhood. Familiarity with the clinical course and imaging
      appearances of the variable CNS diseases is helpful in making correct
      differential diagnoses and in prompting timely treatment. This article reviews
      the clinical courses, pathologic findings, and imaging features of the most
      common viral infections that may involve the CNS of neonates and infants,
      including congenital and neonatal CNS viral infections, common CNS viral
      infections, and parainfectious encephalomyelitis.

PMID- 18319159
TI  - Imaging of slow viruses.
AB  - The symptoms associated with slow viral or prion diseases of the central nervous
      system tend to have multiple neurologic symptoms, and different patients may
      present with different symptoms. This review discusses the most common slow virus
      infections and their imaging findings.

PMID- 18319160
TI  - Imaging of acute disseminated encephalomyelitis.
AB  - Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease
      of the central nervous system typically affecting the gray and the white matter
      of the brain and spinal cord in multiple locations. In the acute stages, ADEM is
      characterized histologically by perivenous edema, demyelination, and infiltration
      with macrophages and lymphocytes, with relative axonal sparing, whereas the late
      course of the disease is characterized by perivascular gliosis.

PMID- 18319161
TI  - Prion protein disease and neuropathology of prion disease.
AB  - Human prion diseases, in common with other neurodegenerative diseases, may be
      sporadic or inherited and are characterized by the accumulation of cellular
      proteins accompanied by neuronal death and synaptic loss. Prion diseases are,
      however, unique in being transmissible. Central to the pathogenesis of all forms
      of prion disease is the prion protein. This article provides a brief overview of
      the biology of human prion diseases followed by a more in-depth discussion of the
      neuropathology of these diseases, including features of neuroradiologic
      relevance.

PMID- 18319162
TI  - Prion infections of the brain.
AB  - Prions are a rare cause of human disease but very important to recognize because
      of their potential for transmissibility and uniformly severe outcome. MR imaging
      plays an extremely important role in early diagnosis, especially with diffusion
      weighted and fluid-attenuated inversion recovery images, which are the most
      sensitive for depicting prion-induced brain lesions. The lesions are
      characteristically shown as ribbons of cortical hyperintensity, or basal ganglia
      or thalamic hyperintensity. The cortical and deep lesions may appear alone or
      together, and although usually bilateral and symmetric, they may be asymmetric or
      purely unilateral. When these MRI findings are observed in an appropriate
      clinical context, the diagnosis of prion disease is very likely.

PMID- 18319164
TI  - Dental implants in children, adolescents, and young adults. Preface.

PMID- 18319166
TI  - Dental implants, growth of the jaws, and determination of skeletal maturity.

PMID- 18319167
TI  - Dental implants in the management of nonsyndromal oligodontia.

PMID- 18319168
TI  - Use of dental implants in the management of syndromal oligodontia.

PMID- 18319169
TI  - Use of dental implants in the management of dental malformations.

PMID- 18319170
TI  - Use of dental implants in the management of cleft lip and palate.

PMID- 18319171
TI  - Rehabilitation of trauma using dental implants.

PMID- 18319172
TI  - Reconstruction of ablative defects using dental implants.

PMID- 18319173
TI  - Facilitation of orthodontics and orthognathic surgery using dental implants.

PMID- 18319174
TI  - Distraction osteogenesis using dental implants.

PMID- 18319175
TI  - Obstetric anesthesia. Foreword.

PMID- 18319176
TI  - Obstetric anesthesia. Preface.

PMID- 18319177
TI  - Anticoagulation in pregnancy and neuraxial blocks.
AB  - The peripartum management of the anticoagulated parturient represents a
      significant clinical challenge to both the obstetrician and the anesthesiologist.
      This review discusses the causes of thrombosis in the pregnant population, the
      anticoagulants used for prophylaxis, and treatment of these disorders, along with
      recommendations for neuraxial blockade in parturients who receive peripartum
      anticoagulation.

PMID- 18319178
TI  - Neurological infections after neuraxial anesthesia.
AB  - Infection is the commonest cause of serious neurologic sequelae of neuraxial
      anesthesia. The incidence depends on operator skill and patient population.
      Meningitis, a complication of dural puncture, is usually caused by viridans
      streptococci. The risk factors are dural puncture during labor, no mask and poor
      aseptic technique, vaginal infection and bacteremia. Epidural abscess is a
      complication of epidural catheterization, route of entry the catheter track and
      the organism usually the staphylococcus. Principal risk factors are prolonged
      catheterization, poor aseptic technique and traumatic insertion. Prevention
      includes wearing a mask, using a full sterile technique, avoiding prolonged
      catheterization and prescribing antibiotics in a high-risk situation.

PMID- 18319179
TI  - Major obstetric hemorrhage.
AB  - Major obstetric hemorrhage remains the leading cause of maternal mortality and
      morbidity worldwide, and is associated with a high rate of substandard care. A
      well-defined and multidisciplinary approach that aims to act quickly and avoid
      omissions or conflicting strategies is key. The most common etiologies of
      hemorrhage are abruptio placenta, placenta previa/accreta, uterine rupture in the
      antepartum period and retained placenta, uterine atony, and genital-tract trauma
      in the postpartum period. Basic treatment of postpartum hemorrhage relies on
      manual removal of the placenta or manual exploration of the uterus plus bladder
      emptying and oxytocin administration. If this does not arrest bleeding, or if
      there is any suspicion of genital-tract trauma, examination of the vagina and
      cervix with appropriate valves and analgesia/anesthesia must follow quickly.
      Postpartum uterine atony resistant to oxytocin must be treated with prostaglandin
      within 15 to 30 minutes; uterine balloon tamponade can be also useful at this
      stage. Aggressive transfusion therapy and resuscitation are mandatory in major
      obstetric hemorrhage. Specific invasive treatment must be considered within no
      more than 30 to 60 minutes, if previous measures have failed -- and even earlier
      in some particular etiologies. The two main options are radiologic embolization
      and surgical artery ligations. Recombinant factor VIIa may also be considered,
      but should not delay the performance of a life-saving procedure such as
      embolization or surgery. Hysterectomy must be implemented when all other
      interventions have failed.

PMID- 18319180
TI  - The historical narrative: tales of professionalism?
AB  - The historical narrative is a story told to illustrate a point, however
      subconsciously. The "giants" of obstetric anesthesia -- Simpson, Snow, Apgar --
      and countless other less well-known physicians all contributed to the history of
      obstetric anesthesia. We remember them by retelling this history to illustrate
      elements of professionalism and how we as a profession wish to act. The Physician
      Charter is an excellent first approximation of a workable definition of this
      quality, which can and does change over time. By using the three principles and
      10 professional responsibilities as a template, the past comes alive as a
      teaching method to each and every obstetric anesthesiologist.

PMID- 18319181
TI  - Vasopressors in obstetrics.
AB  - Hypotension is a common, treatable side effect of neuraxial anesthesia, which has
      significant side effects for the mother and demonstrable biochemical effects in
      the fetus. It is clear that a shift in management of hypotension in the obstetric
      population is in order, but we can only speculate on the benefits for the
      compromised fetus due to the lack of available information in that patient
      population.

PMID- 18319182
TI  - Obstetric anesthesia: outside the labor and delivery unit.
AB  - The maternal mortality rate in the United States has stagnated for the past 2
      decades. To further lower morbidity and mortality, we must take a broader
      perspective. When a pregnant woman is treated in a nonobstetric part of the
      hospital, care must adapt quickly to her special needs. Excessive concern as to
      medication, radiation, and litigation may render her care neither safe, timely,
      efficient, effective, nor patient-centered. Anesthesiologists can significantly
      improve the care of the pregnant patient by applying their uniquely broad-based
      skills, experience, and knowledge outside the labor unit.

PMID- 18319183
TI  - Principles and practices of obstetric airway management.
AB  - Although maternal mortality resulting from anesthesia is declining, airway causes
      predominate. Although there are many physiologic and nonphysiologic factors that
      contribute to potential difficulties when intubating parturients, whether or not
      the maternal airway is more difficult anatomically continues to be debatable.
      What is more certain, however, is that the situation is more complex than other
      settings. Vigilance, avoidance, and preparation continue to be key to management.
      In cases of unexpected difficulty, which likely are unavoidable, several rescue
      devices may be helpful.

PMID- 18319184
TI  - Anesthesia for the pregnant HIV patient.
AB  - Numbers of HIV-infected individuals across the globe are increasing, as is the
      proportion of women infected with HIV. However, better understanding of the HIV
      virus, and rapidly evolving treatments has provided hope for millions of people
      world-wide. In the pregnant population, recent understanding of factors
      influencing vertical transmission has enabled dramatic reductions in mother-to
      child transmission. The anesthesiologist is likely to encounter HIV-infected
      parturients in the delivery suite as part of routine practice, and should be
      aware of the current trends in obstetric -- as well as anesthetic -- best
      practice and management.

PMID- 18319185
TI  - Ultrasound-facilitated epidurals and spinals in obstetrics.
AB  - Regional anesthesia is currently the gold standard of practice for pain control
      in obstetrics. Failures and complications of regional anesthesia can be related
      to many causes, one of the most important being the blind nature of such
      techniques. The practice of epidurals and spinals relies primarily on the
      palpation of anatomic landmarks that are not always easy to find. Ultrasound has
      recently been introduced into clinical anesthesia to facilitate lumbar spinals
      and epidurals. The use of preprocedure ultrasound imaging or, eventually, real
      time ultrasound guidance should improve not only clinical practice, but also
      teaching. This article describes the techniques, challenges, and benefits related
      to the use of ultrasound in guiding lumbar spinals and epidurals.

PMID- 18319186
TI  - Can medical simulation and team training reduce errors in labor and delivery?
AB  - Patient safety is one of the most pressing challenges in health care today, and
      there is no question that medical errors occur and that patients are worried
      about them. Currently, there is a belief that the availability of medical
      simulations and the knowledge gained from the science of team training may
      improve patient outcomes, and there is a paradigm shift occurring in many
      universities and training programs. This article discusses two strategies that,
      when combined, may reduce medical error in the labor and delivery suite: team
      training and medical simulation.

PMID- 18319187
TI  - The use of remifentanil in obstetrics.
AB  - Remifentanil has been proposed as the most suitable systemic opioid for use in
      obstetrics. Although the onset and offset are rapid, it cannot achieve maximum
      effect within the time period of a single uterine contraction. Nevertheless, it
      provides worthwhile analgesia mainly for the first stage of labor with
      consistently high maternal satisfaction. Maternal oxygen desaturation limits the
      dose and suitable monitoring during use is advised. As an adjunct to general
      anesthesia, it is successful in blunting responses to airway manipulation and
      providing hemodynamic stability in high-risk women. Neonatal effects when used in
      labor are minimal, but when combined with general anesthesia neonatal depression
      is unpredictable and more likely with an infusion dose greater than 0.1
      microg/kg/min.

PMID- 18319188
TI  - Pharmacogenetics and obstetric anesthesia.
AB  - The ultimate goal of pharmacogenetics research is to help doctors tailor doses of
      medicines to a person's unique genetic make-up, making medicines safer and more
      effective for everyone. Although there still are no guidelines and immediate
      clinical implications for practitioners providing analgesia or anesthesia, it is
      essential to realize that trial-and-error pharmacotherapy and one-size-fits-all
      dogmas are bound to die. This review briefly outlines the genetic variability of
      pharmacokinetics and pharmacodynamics and discusses selected fields relevant to
      obstetric anesthesiologists for whom the challenges of translating
      pharmacogenetics to clinical practice hopefully are on their way.

PMID- 18319189
TI  - Maternal morbidity, mortality, and risk assessment.
AB  - Maternal deaths in developed countries continue to decline and are rare. Maternal
      mortality statistics are essentially similar in the United States and United
      Kingdom. However, the situation is completely different in developing countries,
      where maternal mortality exceeds 0.5 million every year. This article not only
      assesses morbidity risks in some of the leading causes of maternal death but also
      highlights strategies to minimize the risks and to prevent maternal morbidity and
      mortality.

PMID- 18319190
TI  - Adsorption of a few heavy metals on natural and modified kaolinite and
      montmorillonite: a review.
AB  - The feasibility of using two important and common clay minerals, kaolinite and
      montmorillonite, as adsorbents for removal of toxic heavy metals has been
      reviewed. A good number of works have been reported where the modifications of
      these natural clays were done to carry the adsorption of metals from aqueous
      solutions. The modification was predominantly done by pillaring with various
      polyoxy cations of Zr4+, Al3+, Si4+, Ti4+, Fe3+, Cr3+or Ga3+, etc. Preparation of
      pillared clays with quaternary ammonium cations, namely, tetramethylammonium-,
      tetramethylphosphonium- and trimethyl-phenylammonium-, N'-didodecyl-N, N'
      tetramethylethanediammonium, etc, are also common. Moreover, the acid treatment
      of clays often boosted their adsorption capacities. The adsorption of toxic
      metals, viz., As, Cd, Cr, Co, Cu, Fe, Pb, Mn, Ni, Zn, etc., have been studied
      predominantly. Montmorillonite and its modified forms have much higher metal
      adsorption capacity compared to that of kaolinite as well as modified-kaolinite.

PMID- 18319192
TI  - Temporal-spatial expressions of p27kip1 and its phosphorylation on Serine-10
      after acute spinal cord injury in adult rat: Implications for post-traumatic
      glial proliferation.
AB  - P27kip1, as a member of Cip/Kip family of cyclin-dependent kinase inhibitors,
      plays important roles in cell cycle regulation and neurogenesis in the developing
      central nervous system. Serine-10 is the major phosphorylation site of p27kip1,
      and post-translational regulation of p27kip1 by different phosphorylation events
      is critical for its function. To elucidate the expressions and possible functions
      of p27kip1 and its phosphorylation in central nervous system lesion and repair,
      we performed an acute spinal cord contusion injury model in adult rats. Our work
      studied the temporal-spatial expression patterns of p27kip1 and Serine-10
      phosphorylated p27kip1 (p-p27s10). Western blot analysis showed p27kip1 level
      significantly decreased at day 3 after damage, while p-p27s10 was detected at a
      high-level at the same time reaching the uninjured level. Moreover,
      immunofluorescence double labeling suggested these changes were striking in
      microglia and astrocytes, which were largely proliferated. Immunohistochemical
      analysis revealed subcellular localization changes of p27kip1 and p-p27s10
      staining between nucleus and cytoplasm after injury in about 20% of total
      positive cells including neurons and glial cells. We also investigated the
      increased interactions of p27kip1 and p-p27s10 with CRM1 3 days after injury by
      co-immunoprecipitation studies. Taken together, we hypothesized spinal cord
      injury stimulated mitogenic signals to induce a serine-threonine kinase KIS
      (kinase interacting stathmin) to phosphorylate p27kip1 on Serine-10, so that
      p27kip1 could bind to CRM1 and be exported from nuclei for degradation. Such an
      event facilitated cell cycle progression of glial cells, especially microglia and
      astrocytes which had a prevalent proliferation.

PMID- 18319193
TI  - Experiment investigation of La(1-x)SrxMnO3 by high-resolution X-ray emission and
      spin-polarized X-ray absorption spectroscopy.
AB  - Big changes in resistivity along with the changing of local structure in some
      oxide systems, such as high-temperature superconductors and colossal
      magnetoresistance system, strongly suggest the need of a systematic investigation
      of their local electronic and atomic structures. In this work we present the high
      resolution X-ray emission spectra and the spin-polarized X-ray absorption near
      edge spectroscopy (SPXANES) data at the Mn K-edge in the La(1-x)Sr(x)MnO(3). This
      experiment is based on a high-resolution large-acceptance crystal analyzer based
      on Si (111) and optimized for X-ray fluorescence spectroscopy. With a spherical
      bent crystal monochromator, a Mn Kbeta emission spectra with high resolution was
      obtained with a short collection time and SPXANES spectra of La(1-x)Sr(x)MnO(3)
      at room temperature were also measured at high temperature.

PMID- 18319195
TI  - The psychosocial impact of epilepsy in Czech children: what are causative factors
      of differences during ten years interval?
AB  - Epilepsy is the most common chronic neurological condition in childhood. In this
      paper we present results of analysis of a comparative survey, using data derived
      from 34-item questionnaire completed by 2 groups of children with epilepsy from
      the whole Czech Republic. The first group (1,217 children) was invited to
      complete the questionnaire in 1995, the second group (612 children) in 2004. The
      greatest attention is usually paid to the "biological" characteristics of
      epilepsy like control of seizures or adverse effects of medication. However,
      children's perception or feelings about epilepsy and interferences with their
      everyday life (school, socializing, holidays, leisure time...) seem's to be at
      least of the same importance. That's why our main objective was to examine
      exactly such psychosocial aspects of quality of life (QOL) and we targeted to
      identify any potential shift of children's perception over the last 10 years.
      Three principal informations arised out of this analysis: during the 10 years
      period adverse effects of antiepileptic drugs (AEDs) became less frequent,
      probably in accordance with the shift towards the use of new AEDs. The second
      group in feels to be less restricted in personal, social and sporting activities 
      most probably because they have generally achieved better control of seizures.
      The children admitted better awareness about epilepsy among teachers and friends
      over 10 years. The study has provided important information about the level of
      psychosocial QOL of children with epilepsy in the Czech Republic and showed a
      slight shift towards optimism in thinking and feeling of children with epilepsy
      during the 10-years period.

PMID- 18319196
TI  - Epilepsia, epileptiform abnormalities, non-right-handedness, hypotonia and severe
      decreased IQ are associated with language impairment in autism.
AB  - The aim of this study was to categorize speech problems in autistic children in a
      manner allowing recognition of associated risk factors. We were specifically
      interested in the role of epilepsy and epileptiform activity in EEG in autistic
      patients since these dynamic processes can influence each other. We combined
      subtypes of autism with degrees of their functionality and we selected three
      speech endpoints: i) delayed development of speech, ii) complete mutism and iii)
      regression of speech. We retrospectively examined 205 autistic children (boys
      145/70.7%, mean age 10 years). Median IQ was 55 (15;104) and median Childhood
      Autism Rating Scale (CARS) ranged within 38 (32;48). Univariate and multivariate
      logistic regression helped to define clinical and diagnostic factors that were
      significantly associated with speech endpoints. Epileptic seizures, epileptiform
      EEG abnormalities, non-right-handedness, hypotonia and severe decreased IQ score
      were found to be the most important mutually independent factors contributing to
      the increased risk of speech-related problems in patients with ASD.

PMID- 18319197
TI  - Language lateralization in children with pre- and postnatal epileptogenic lesions
      of the left hemisphere: an fMRI study.
AB  - Functional MRI was used to evaluate factors influencing hemispheric dominance for
      language in 34 children suffering from intractable focal epilepsy due to left
      hemispheric lesion of pre- (n = 19) or postnatal (n = 15) origin. Nineteen
      children (56%) exhibited pronounced left-hemispheric language dominance.
      Significant co-activation of the right hemisphere or a complete language shift to
      this hemisphere was present in 15 children (44%). Atypical language
      representation was detected in 6 children (31,6%) with developmental pathology
      and in 9 patients (60%) with acquired epileptogenic lesion. Younger age at
      epilepsy onset and longer duration of epilepsy correlated significantly with
      atypical language presentation (p < 0,017 and p < 0,025). Whereas lesser tendency
      of prenatal lesions to displace cortical language centers did not reach
      statistical significance in simple paired tests, multiple logistic regression
      analysis viewed positive interaction between language shift, etiology and age at
      epilepsy onset. In conclusion, the language network reorganization was strongly
      influenced by both, the age at epilepsy onset and duration of epilepsy, and to a
      lesser degree by the character of the epileptogenic lesion, either developmental
      or acquired postnatally.

PMID- 18319198
TI  - Epileptiform activity in children with developmental dysphasia: quantification of
      discharges in overnight sleep video-EEG.
AB  - We present results of analysis of overnight sleep video-EEG in 8 patients with
      developmental dysphasia and rolandic discharges. We evaluated the incidence of
      epileptiform discharges (expressed as paroxysmal activity density) at one or more
      electrodes in different sleep stages in three different periods of the night
      (after falling asleep, around midnight and before awakening). The difference of
      paroxysmal activity density was never higher than 21%, indicating that
      quantifying the discharges in the whole night recording is not necessary. We also
      showed that two independent foci may differ in the frequency of discharges. We
      propose a scheme for evaluation of EEG reflecting both frequency and distribution
      of discharges.

PMID- 18319199
TI  - Hypoxia-induced changes of seizure susceptibility in immature rats are modified
      by vigabatrin.
AB  - The effects of hypoxia on susceptibility to pentylenetetrazol (PTZ)-induced
      seizures were assessed in juvenile rats. Animals at postnatal (P) day 25 were
      exposed to hypobaric hypoxia (simulated altitude of 7000 m) for 8 h PTZ in a dose
      of 100 mg/kg was injected 1, 3 or 7 days later and latency, pattern and severity
      of seizures were registered. Mortality due to seizures was also evaluated. Two
      seizure types were evaluated: minimal mostly clonic seizures (mMS) and
      generalized tonic clonic seizures (GTCS). To study protective effects of
      vigabatrin (600 mg/kg, i.p.), drug was injected either 24 h before or immediately
      after hypoxia exposure. Non-hypoxic animals of corresponding age were used for
      comparison as controls. In non-hypoxic controls, administration of vigabatrin had
      pro-convulsive effects in intervals from 3 days up to 1 week - incidence of GTCS
      increased by 56-57%. Hypoxia exposure resulted to increased seizure
      susceptibility three days later, incidence of generalized tonic clonic seizures
      increased by 60% and latency to both seizure types shorter than in non-hypoxic
      controls. Also, mortality due to seizures was higher (by 58%). In other
      intervals, there was no difference between hypoxic and non-hypoxic animals.
      Vigabatrin administered 24 h before hypoxia led to significant decrease of
      seizure-induced mortality in intervals 1 and 3 days. Administration of vigabatrin
      immediately after hypoxia exposure resulted in decreased seizure severity when
      assessed 3 days later. Our data suggest that hypobaric hypoxia transiently
      increases seizure susceptibility. This effect is partially abolished by
      vigabatrin administered after hypoxia exposure.

PMID- 18319200
TI  - Effects of a GABA-B receptor agonist baclofen on cortical epileptic
      afterdischarges in rats.
AB  - Inhibition mediated by GABA-B receptors can play a role in epilepsy. We therefore
      studied its involvement in cortical epileptic afterdischarges in adult rats by
      means of a GABA-B receptor agonist baclofen. Three different experiments were
      performed with cortical epileptic afterdischarges and an additional experiment
      studied possible effect of baclofen on cortical interhemispheric (transcallosal)
      evoked potentials. Baclofen was administered intraperitoneally in doses of 3 or 6
      mg/kg. In contrast to a marked proconvulsant action of a GABA-B receptor
      antagonist baclofen did not exhibit clear anticonvulsant action against EEG
      afterdischarges but a moderate effect on motor phenomena was observed. On the
      contrary, it tended to decrease threshold intensities for individual epileptic
      phenomena. Augmentation of postictal refractoriness by baclofen was found only
      with a short poststimulation interval (2 min). Cortical interhemispheric
      responses induced by single pulses were influenced only moderately by baclofen;
      paired-pulse potentiation induced by short intervals between stimuli was not
      changed but there was a depression of the second response induced 200 and 250 ms
      after the first one with the 6 mg/kg dose of baclofen. Failure of baclofen to
      exhibit an expected anticonvulsant activity might be due to a complexity of GABA
      B inhibitory system (pre- as well as postsynaptic localization of GABA-B
      receptors).

PMID- 18319201
TI  - Psychogenic non-epileptic seizures, prospective clinical experience: diagnosis,
      clinical features, risk factors, psychiatric comorbidity, treatment outcome.
AB  - In our study, we evaluated 249 patients with refractory seizures using video-EEG
      monitoring. In this sample, we identified 56 (22.5%) patients with psychogenic
      non-epileptic seizures - PNES only. Spontaneous seizures were recorded in 49
      (87%) patients with PNES. Suggestive seizure induction using intravenous saline
      placebo was successful in 77.1% of induced PNES cases. Disease duration prior to
      PNES diagnosis was quite long. Prolonged past and current intake of high number
      of different antiepileptic drugs was also typical for these patients. We
      evaluated ictal PNES semiology. Whereas ictal EEG was normal in all PNES
      patients, interictal EEG was abnormal in 46.4%. Brain MRI was abnormal in 30.4%.
      Personality disorders were the most frequent psychiatric co-morbidity (in 44.6%
      of PNES patients), emotionally unstable (borderline) personality disorder was
      predominant (in 32.1% of PNES patients). Risk factors for epilepsy misdiagnosis
      and PNES manifestation are discussed. Therapeutic outcome after two years of
      combined treatment (psychopharmacotherapy and/or psychotherapy) is presented;
      approximately one third of patients were seizure-free following two years of
      treatment, one third of patients were responders (>or= 50% reduction in seizure
      frequency) and one third did not respond to treatment.

PMID- 18319202
TI  - Magnetic resonance spectroscopy of the thalamus in patients with mesial temporal
      lobe epilepsy and hippocampal sclerosis.
AB  - PURPOSE: to investigate potential neuronal dysfunction within the thalamus in
      patients suffering from mesial temporal lobe epilepsy with hippocampal sclerosis
      (MTLE/HS). METHODS: we examined twenty epileptic patients suffering from mesial
      temporal lobe epilepsy with hippocampal sclerosis (17 females, 3 males) and
      twenty sex- and age-matched healthy controls. H MR spectroscopic imaging (SI) was
      performed over the right and left thalamus in all patients and controls. In
      addition both hippocampi were investigated by the H MR spectroscopic single voxel
      (SV) technique in both groups. RESULTS: statistical analysis of compared data in
      both groups demonstrated that the total thalamic NAA level was significantly
      decreased in patients with MTLE/HS as compared to healthy controls. Detailed
      analysis revealed a statistically significant reduction of NAA, NAA/Cr and
      NAA/(Cr+Cho) ratios in the thalamus ipsilateral to hippocampus affected with
      hippocampal sclerosis in patients compared to controls, while no significant
      changes were observed in the thalamus contralateral to sclerotic hippocampus. A
      comparison of values in ipsilateral and contralateral thalami in patients showed
      statistically significant difference with lower values of NAA and both ratios in
      the ipsilateral thalamus. Previously reported reduced hippocampal concentration
      of NAA, NAA/Cr and NAA/(Cr+Cho) ratios on the side of hippocampal sclerosis
      compared with contralateral hippocampus in patients and both hippocampi in
      controls was confirmed. CONCLUSIONS: the present MRS data clearly indicate
      neuronal dysfunction within the thalamus ipsilateral to the sclerotic hippocampus
      of patients with mesial temporal lobe epilepsy. In agreement with other recent
      functional and structural neuroimagings our results confirm the role of the
      ipsilateral thalamus in the medial temporal/limbic epileptic network.

PMID- 18319203
TI  - Stereotactic amygdalohippocampectomy for temporal lobe epilepsy: promising
      results in 16 patients.
AB  - OBJECTIVES: Minimally invasive procedures for treating temporal lobe epilepsy
      have been investigated recently, namely stereotactic and gamma knife
      amygdalohippocampectomy (AHE). However, the results are not fully satisfactory.
      Our aim was to evaluate efficacy and side-effects of stereotactic AHE mimicking
      the neurosurgical procedure in terms of extent of the lesion. METHODS: 16
      consecutive patients were assessed using VEEG, MRI, FDG-PET and WADA test. All
      had definite pharmacoresistant medial temporal lobe epilepsy. The stereotactic
      AHE was performed on the Leksell stereotactic system. All lesions exceeded 40 mm
      along the long axis of the hippocamus. RESULTS: Seizure outcome was favourable on
      one year follow-up: 12 patients (75%) were seizure-free (Engel I), three (19%)
      were Engel II, and one (6%) was Engel III. Side-effects were mild, lasting up to
      7 days: cephalea, meningeal syndrome with sterile CSF in three subjects, and CSF
      leak lasting up to 3 days in seven subjects. CONCLUSION: Stereotactic AHE
      encompassing sufficient volume of the amygdalohippocampal complex appears to be
      safe, effective, and free from long-term side-effects.

PMID- 18319204
TI  - Clinical characteristics in patients with hippocampal sclerosis with or without
      cortical dysplasia.
AB  - BACKGROUND: Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS)
      constitutes a distinct clinical syndrome with variable pathogenesis.
      Extrahippocampal regions may be affected in MTLE/HS, association with cortical
      dysplasia is common and temporal polar cortex is frequently involved in seizure
      onset. Patients with dual pathology may have favourable outcome from the surgery
      provided that both pathologies are removed. The aim of the study was to review
      clinical variables of MTLE/HS patients in order to distinguish preoperatively
      patients with associated microscopic cortical dysplasia in the temporal pole.
      METHODS: A series of 38 patients with the clinical diagnosis of MTLE and
      histopathologically proven HS were analysed. Patients were divided into two
      groups on the basis of histopathological finding in the temporal polar cortex: HS
      associated with malformation of cortical development (group HS+, n = 19) and a
      group with isolated HS (group HS, n = 19). Demographic, clinical, electrographic
      and seizure semiology variables were obtained and their prevalence compared
      between both groups. RESULTS: At least one insult was identified in early
      childhood history of 18 patients in the HS group in comparison to 10 patients in
      the HS+ group (p < 0.01). Complicated febrile seizures were found in both groups
      with similar prevalence, the history of early childhood CNS infection prevailed
      in the HS group (p < 0.01). Absence of aura was reported in HS group only.
      Patients in the the HS+ group had earlier surgery (p < 0.05) but the seizure
      outcome was comparable between groups. CONCLUSIONS: Microscopic dual pathology is
      common in MTLE/HS patients. This group of patients is difficult to distinguish
      preoperatively on the basis of noninvasive electrographic features or ictal
      clinical semiology. Detailed information regarding the possible precipitating
      insult in the history may be of critical importance.

PMID- 18319205
TI  - Sexual functions in women with focal epilepsy. A preliminary study.
AB  - We analyzed sexual function in 29 women suffering from focal epilepsy using the
      Female Sexual Function Index, Beck Depression Inventory, Beck Anxiety Inventory
      and a battery of laboratory tests were performed to find possible correlations
      and differences. A total FSFI score lower than the predefined cut-off score was
      found in 20.7% women and the presence of at least one subtype of sexual
      dysfunction was found in 51.7% of them. The most frequent dysfunction was lack of
      lubrication, which occurred in 34.5% of patients. A higher depression score was
      significantly correlated with a worse total score of Female Sexual Function Index
      and with decreased score of lubrication, satisfaction and pain. Patients who were
      seizure-free had better total score of Female Sexual Function Index and score of
      lubrication, orgasm and pain in comparison to patients who were not seizure-free.
      A higher anxiety scale was correlated only with lower satisfaction. We found a
      statistically significant correlation of reduced desire and use of carbamazepine
      and with lower dehydroepiandrosterone sulphate and free-androgene index. Reduced
      arousal was also correlated with the use of carbamazepine and lower
      dehydroepiandrosterone sulphate. Patients with a combination of complex partial
      and generalized tonic-clonic seizures had a worse total sexual function score and
      pain score than those with complex partial and generalized tonic-clonic seizures
      only. Sexual dysfunctions are relatively common problems in epileptic women with
      focal epilepsy. Prospective studies, including a control group, are needed.

PMID- 18319206
TI  - Nocturnal activity positively correlated with auditory sensitivity in noctuoid
      moths.
AB  - We investigated the relationship between predator detection threshold and
      antipredator behaviour in noctuoid moths. Moths with ears sensitive to the
      echolocation calls of insectivorous bats use avoidance manoeuvres in flight to
      evade these predators. Earless moths generally fly less than eared species as a
      primary defence against predation by bats. For eared moths, however, there is
      interspecific variation in auditory sensitivity. At the species level, and when
      controlling for shared evolutionary history, nocturnal flight time and auditory
      sensitivity were positively correlated in moths, a relationship that most likely
      reflects selection pressure from aerial-hawking bats. We suggest that species
      specific differences in the detection of predator cues are important but often
      overlooked factors in the evolution and maintenance of antipredator behaviour.

PMID- 18319207
TI  - Female sperm limitation in natural populations of a sexual/asexual mating complex
      (Poecilia latipinna, Poecilia formosa).
AB  - In sperm-dependent sexual/asexual mating systems, male mate choice is critical
      for understanding the mechanisms behind apparent stability observed in natural
      populations. The gynogenetic Amazon molly (Poecilia formosa) requires sperm from
      sexual males (e.g. Poecilia latipinna) to trigger embryogenesis, but inheritance
      is strictly maternal. Consequently, males should try to avoid or reduce the cost
      of mating with asexuals. We investigated male mate choice by documenting the
      presence of sperm in natural populations and found that a higher proportion of
      sexual females had sperm than asexuals. In addition, among those females that had
      sperm, sexuals had more sperm than asexuals. Our results hint at a role for male
      mate choice as a stabilizing factor in such systems.

PMID- 18319208
TI  - Top-down causation by information control: from a philosophical problem to a
      scientific research programme.
AB  - It has been claimed that different types of causes must be considered in
      biological systems, including top-down as well as same-level and bottom-up
      causation, thus enabling the top levels to be causally efficacious in their own
      right. To clarify this issue, the important distinctions between information and
      signs are introduced here and the concepts of information control and functional
      equivalence classes in those systems are rigorously defined and used to
      characterize when top-down causation by feedback control happens, in a way that
      is testable. The causally significant elements we consider are equivalence
      classes of lower level processes, realized in biological systems through
      different operations having the same outcome within the context of information
      control and networks.

PMID- 18319209
TI  - Dynamic social networks and the implications for the spread of infectious
      disease.
AB  - Understanding the nature of human contact patterns is crucial for predicting the
      impact of future pandemics and devising effective control measures. However, few
      studies provide a quantitative description of the aspects of social interactions
      that are most relevant to disease transmission. Here, we present the results from
      a detailed diary-based survey of casual (conversational) and close contact
      (physical) encounters made by a small peer group of 49 adults who recorded 8,661
      encounters with 3,528 different individuals over 14 non-consecutive days. We find
      that the stability of interactions depends on the intimacy of contact and social
      context. Casual contact encounters mostly occur in the workplace and are
      predominantly irregular, while close contact encounters mostly occur at home or
      in social situations and tend to be more stable. Simulated epidemics of casual
      contact transmission involve a large number of non-repeated encounters, and the
      social network is well captured by a random mixing model. However, the stability
      of the social network should be taken into account for close contact infections.
      Our findings have implications for the modelling of human epidemics and planning
      pandemic control policies based on social distancing methods.

PMID- 18319210
TI  - Fluid-particle dynamics in canalithiasis.
AB  - The semicircular canals (SCCs; located in the inner ear) are the primary sensors
      for angular motion. Angular head movements induce a fluid flow in the SCCs. This
      flow is detected by afferent hair cells inside the SCCs. Canalithiasis is a
      condition where small particles disturb this flow, which leads to benign
      paroxysmal positional vertigo (top-shelf vertigo). The present work investigates
      the interaction between the fluid flow and the particles on the basis of an
      idealized analytical model. Numerical solutions of the full model and a thorough
      analytical study of the linearized model reveal the principal mechanisms of
      canalithiasis. We propose a set of dimensionless numbers to characterize
      canalithiasis and derive explicit expressions connecting these dimensionless
      numbers directly to the typical clinical symptoms.

PMID- 18319211
TI  - A genetic component of resistance to fungal infection in frog embryos.
AB  - The embryo has traditionally been considered to completely rely upon parental
      strategies to prevent threats to survival posed by predators and pathogens, such
      as fungi. However, recent evidence suggests that embryos may have hitherto
      neglected abilities to counter pathogens. Using artificial fertilization, we show
      that among-family variation in the number of Saprolegnia-infected eggs and
      embryos in the moor frog, Rana arvalis, cannot be explained by maternal effects.
      However, analysed as a within-females effect, sire identity had an effect on the
      degree of infection. Furthermore, relatively more eggs and embryos were infected
      when eggs were fertilized by sperm from the same, compared with a different,
      population. These effects were independent of variation in fertilization success.
      Thus, there is likely to be a significant genetic component in embryonic
      resistance to fungal infection in frog embryos. Early developmental stages may
      show more diverse defences against pathogens than has previously been
      acknowledged.

PMID- 18319212
TI  - Geometry explains the benefits of division of labour in a leafcutter ant.
AB  - Many ant species have morphologically distinct worker sub-castes. This presumably
      increases colony efficiency and is thought to be optimized by natural selection.
      Optimality arguments are, however, often lacking in detail. In ants, the benefits
      of having workers in a range of sizes have rarely been explained mechanistically.
      In Atta leafcutter ants, large workers specialize in defence and also cut fruit.
      Fruit is soft and can be cut by smaller workers. Why, therefore, are large
      workers involved? According to the geometry hypothesis, cutting large pieces from
      three-dimensional objects like fruit is enhanced by longer mandibles. By
      contrast, long mandibles are not needed to cut leaves that are effectively two
      dimensional. Our results from Atta laevigata support three predictions from the
      geometry hypothesis. First, larger workers cut larger fruit pieces. Second, the
      effect of large size is greater in cutting fruit than leaves. Third, the size of
      fruit pieces cut increases approximately in proportion to the cube of mandible
      length. Our results are a novel mechanistic example of how size variation among
      worker ants enhances division of labour.

PMID- 18319213
TI  - Size-dependent resistance of protected areas to land-use change.
AB  - One of the major threats facing protected areas (PAs) is land-use change and
      habitat loss. We assessed the impact of land-use change on PAs. The majority of
      parks have been effective at protecting the ecosystems within their borders, even
      in areas with significant land-use pressures. More in particular, the capacity of
      PAs to slow down habitat degradation and to favour habitat restoration is clearly
      related to their size, with smaller areas that on average follow the dominant
      land-use change pattern into which they are embedded. Our results suggest that
      small parks are not going to be viable in the long term if they are considered as
      islands surrounded by a 'human-dominated ocean'. However, small PAs are, in many
      cases, the only option available, implying that we need to devote much more
      attention to the non-protected matrix in which PAs must survive.

PMID- 18319214
TI  - Are the small human-like fossils found on Flores human endemic cretins?
AB  - Fossils from Liang Bua (LB) on Flores, Indonesia, including a nearly complete
      skeleton (LB1) dated to 18kyr BP, were assigned to a new species, Homo
      floresiensis. We hypothesize that these individuals are myxoedematous endemic
      (ME) cretins, part of an inland population of (mostly unaffected) Homo sapiens.
      ME cretins are born without a functioning thyroid; their congenital
      hypothyroidism leads to severe dwarfism and reduced brain size, but less severe
      mental retardation and motor disability than neurological endemic cretins. We
      show that the fossils display many signs of congenital hypothyroidism, including
      enlarged pituitary fossa, and that distinctive primitive features of LB1 such as
      the double rooted lower premolar and the primitive wrist morphology are
      consistent with the hypothesis. We find that the null hypothesis (that LB1 is not
      a cretin) is rejected by the pituitary fossa size of LB1, and by multivariate
      analyses of cranial measures. We show that critical environmental factors were
      potentially present on Flores, how remains of cretins but not of unaffected
      individuals could be preserved in caves, and that extant oral traditions may
      provide a record of cretinism.

PMID- 18319215
TI  - Chemical basis of nest-mate discrimination in the ant Formica exsecta.
AB  - Distinguishing nest-mates from non-nest-mates underlies key animal behaviours,
      such as territoriality, altruism and the evolution of sociality. Despite its
      importance, there is very little empirical support for such a mechanism in
      nature. Here we provide data that the nest-mate recognition mechanism in an ant
      is based on a colony-specific Z9-alkene signature, proving that surface chemicals
      are indeed used in ant nest-mate recognition as was suggested 100 years ago. We
      investigated the cuticular hydrocarbon profiles of 10 Formica exsecta colonies
      that are composed almost entirely of a Z9-alkene and alkane component. Then we
      showed that worker aggression is only elicited by the Z9-alkene part. This was
      confirmed using synthetic Z9-alkene and alkane blends matched to the individual
      colony profiles of the two most different chemical colonies. In both colonies,
      only glass beads with 'nest-mate' alkene profiles received reduced aggression.
      Finally, changing the abundance of a single Z9-alkene on live ants was shown to
      significantly increase the aggression they received from nest-mates in all five
      colonies tested. Our data suggest that nest-mate discrimination in the social
      insects has evolved to rely upon highly sensitive responses to relatively few
      compounds.

PMID- 18319216
TI  - CORONA, statins, and heart failure: who lost the crown?

PMID- 18319217
TI  - Coronary artery disease in young women and men with long-standing insulin
      dependent diabetes.
AB  - The prevalence and predictors of coronary artery disease were examined in people
      aged 40 years and younger with insulin-dependent diabetes mellitus. Analysis was
      performed on those who presented between 1999 and 2003 for kidney and/or pancreas
      transplant at the University of Minnesota, as all patients who have diabetes
      mellitus are required to have perioperative cardiology evaluation. The mean age
      was 33.5 +/- 4.4 years for 88 subjects, all had insulin-dependent diabetes
      mellitus, and 33% were dialysis dependent. Severe coronary artery disease was
      found in 18.2% of women and in 24.2% of men. Three-vessel coronary artery disease
      trended less in women (9.1%) compared with men (12.1%). Multivariate predictors
      for severe and 3-vessel coronary artery disease included prior coronary artery
      disease, hypertension duration, and ST-T wave changes on electrocardiogram.
      Coronary artery disease is twice as high as expected in young woman. Studies on
      early management for atherosclerosis are warranted in this high-risk population.

PMID- 18319218
TI  - What is the relationship between myocardial perfusion imaging and coronary artery
      disease risk factors and markers of inflammation?
AB  - The treatment of coronary artery disease (CAD) is clinically measured by
      monitoring changes in venous lipids and inflammatory markers. There is currently
      no established quantified relationship between coronary flow reserve and markers
      of inflammatory CAD. A total of 120 men and women underwent quantified
      measurement of coronary blood flow using SPECT imaging at baseline and 1 year
      later. They had fasting venous blood work obtained at baseline and 1 year later.
      These markers of lipids and inflammation included, total cholesterol, low-density
      lipoprotein cholesterol, very low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, triglycerides, lipoprotein-a, homocysteine, fibrinogen,
      C-reactive protein, and interleukin-6. Regression analysis reveals no general
      statistical relationship between these markers and coronary blood flow as
      measured by myocardial perfusion imaging. However, when changes in indices are
      considered and changes in risk factors are compared with changes in ischemia,
      blood factor based estimates yield an adjusted R2 = 0.31, R = 0.57, P < .0001.
      Initial levels of coronary ischemia cannot be diagnostically inferred from
      baseline values in lipid and inflammatory markers of coronary artery disease.
      When change in coronary blood flow is quantified using SPECT imaging, 6
      independent underlying blood factors provided statistically useful information in
      identifying changes in coronary blood flow. Although the relationship of changes
      is statistically significant ( P < .0001), quantification of coronary blood flow
      by SPECT imaging provides physiologic status information, which cannot be
      inferred from fasting markers of lipids and inflammation status.

PMID- 18319219
TI  - Serum total and high-density lipoprotein phospholipid levels in a population
      based study and relationship to risk of metabolic syndrome and coronary disease.
AB  - The aim of study was to investigate the role of serum total (TPL) and high
      density lipoprotein phospholipids (HDL-pl) as a risk factor in coronary heart
      disease (CHD) and metabolic syndrome (MS). In a random sample, total and HDL-pl
      were measured in 1088 and 642 adults from Turkey, respectively, who have a high
      prevalence of MS; this was done with an enzymatic method that measures total
      phosphatidylcholine, sphingomyelin, and lysophosphatidylcholine. Serum TPL and
      HDL-pl levels were significantly higher in women (TPL, 2.8 mmol/L; HDL-pl, 1.21
      mmol/L) than in men. Strong correlations existed between serum TPL levels and non
      HDL cholesterol (HDL-C), triglycerides, apolipoprotein (apo) B, complement C3,
      and gamma-glutamyltransferase. Non-HDL-C, HDL triglyceride, and apo A-I were
      strongly correlated with HDL-pl. Linear regression analyses revealed HDL-C, apo
      B, triglycerides, diabetes, and female gender as independent significant
      determinants of TPL levels in adults. HDL-C and impaired glucose regulation were
      sole significant variables, together contributing one-quarter of serum HDL-pl.
      Individuals with MS or diabetes had significantly higher TPL concentrations. The
      gender- and age-adjusted odds ratio (OR) of TPL for MS was 1.73 (95% confidence
      interval, 1.35-2.21), whereas the multiadjusted OR of HDL-pl per 1 SD increment
      corresponded to a significantly reduced independent MS likelihood by 26% in women
      (and 18% in the entire group). The multiadjusted OR of HDL-pl for CHD in men and
      women combined was 0.32 (P = .057) corresponding to a reduced CHD likelihood by
      32% per 1 SD increment of HDL-pl. Plasma TPL levels point to an adverse
      relationship to MS, whereas their role in CHD risk needs further investigation.
      HDL-pls, in contrast, mark substantial protection from MS as well as from CHD.

PMID- 18319220
TI  - Achieving vascular risk factor targets: a survey of a London general practice.
AB  - We assessed lipid goal achievement in patients at high risk for vascular events
      from a general practice (London, United Kingdom). Patients were identified as
      those with a prescription for hypolipidaemic medication, a significant (>20%)
      Framingham risk, and from the myocardial infarction register. Two hundred forty
      five patients were currently taking a statin (average dose, 23.1 mg/day).
      Cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein
      cholesterol, and triglycerides changed significantly following statin treatment.
      Of 285 patients who had taken statins at some time point, 11 (3.9%) were
      intolerant, 5 of which subsequently tolerated another statin. Approximately 10.1%
      of patients discontinued statin treatment for unclear reasons. Only 64 patients
      (29.1% of 220) reached the Joint British Societies' Guidelines on Prevention of
      Cardiovascular Disease target of a total cholesterol of <4.0 mmol/L; 50 patients
      (38.8% of 129) reached the low-density lipoprotein-cholesterol target of <2.0
      mmol/L. This value of low-density lipoprotein-cholesterol is similar to that
      recommended by the American Heart Association/American College of Cardiology.
      With regard to the General Medical Services guidelines target for total
      cholesterol, 162 (73.6% of 220) patients reached <or=5.0 mmol/L. The group that
      best achieved target cholesterol (Joint British Societies' Guidelines and General
      Medical Services) were those with comorbidities. In conclusion, while reaching
      General Medical Services targets was satisfactory, the percentage of patients
      reaching Joint British Societies' Guidelines targets was not. This discrepancy
      may reflect the presence of multiple guidelines. The current stricter lipid
      targets are difficult to achieve; possible methods that may be used to improve
      lipids further could involve using combination therapy, statin dose titration,
      and better education.

PMID- 18319221
TI  - Angiographic restenosis in ephesos coronary stents: experience from a large
      medical center in Ankara, Turkey.
AB  - Coronary stent restenosis, which emerges in late periods after implantation, has
      not been completely abolished. Our aim was to investigate the restenosis rates of
      Ephesos coronary stents. In all, 96 patients (66 men) with 135 Ephesos coronary
      stents were included. Control angiograms were performed after 160 +/- 60 days.
      Quantitative coronary analysis was performed during the procedure and control
      angiogram. The stents were divided into 2 groups according to the presence or
      absence of restenosis. Groups were compared with clinical and angiographic
      variables. Restenosis was observed in 31 (23%) of 135 stents. Preprocedure
      percent diameter stenosis was higher (P = .02), whereas minimum lumen diameter (
      P = .02), mean age (P < .001), and hypertension incidence ( P = .043) was less,
      and there was a trend toward smaller stent size ( P = .054) in the restenosis
      group. By multivariate analysis, age <50 years (P < .001) and stent size <3.0 mm
      (P = .016) were independent predictors of restenosis. Ephesos coronary stents
      seems to have acceptable restenosis rates.

PMID- 18319222
TI  - Impaired flow-mediated endothelium-dependent and endothelium-independent
      vasodilation of the brachial artery in patients with atherosclerotic peripheral
      vascular disease.
AB  - A flow-mediated endothelium-dependent vasodilation and endothelium-independent
      nitroglycerin-induced vasodilation were carried out in 70 patients and 15 age
      matched adults without any atherosclerotic risk factors to clarify vascular
      responsiveness in patients with atherosclerotic peripheral vascular disease. The
      percent change in flow-mediated vasodilation was significantly lower in patients
      than in controls (5.4 +/- 0.7% vs 12.8 +/- 2.2%, P < .001). Moreover, the percent
      change in nitroglycerin-induced vasodilation measured after sublingual
      administration of nitroglycerin was lower in patients than in controls (5.8 +/-
      0.6% vs 10.2 +/- 1.5%, P < .01). On multiple regression analysis, none of the
      determinant factors showed a significant correlation with flow-mediated
      vasodilation. In contrast, Fontaine classification was found to be a significant
      predictor for nitroglycerin-induced vasodilation (r = -0.307, P < .05). There is
      a significant positive correlation between nitroglycerin-induced vasodilation and
      ankle-brachial pressure index in the patients. The data showed that vasoditation
      function were markedly impaired in end-stage patients with peripheral vascular
      disease.

PMID- 18319223
TI  - Prescribing practice of general practitioners in Northern Ireland for peripheral
      arterial disease.
AB  - Peripheral arterial disease is prevalent and reflects overall cardiovascular
      disease state. Best medical treatment is the cornerstone of management to reduce
      peripheral arterial disease symptoms and to minimize vascular morbidity and
      mortality. The aim of this study was to assess the prescription practice of
      general practitioners in Northern Ireland for patients with peripheral arterial
      disease. All general practitioners were from the Northern Ireland Professional
      Medical Directory, and a questionnaire was used to determine the prescribing
      patterns for peripheral arterial disease. In all, 468 general practitioners
      responded; 94% prescribed aspirin to nondiabetic patients, and 44.9% prescribed
      statin, with similar results for diabetic patients. Angiotensin-converting enzyme
      inhibitors, multivitamins, and beta-blockers were not often prescribed. Statin
      was prescribed to patients with diabetic peripheral arterial disease at a lower
      cholesterol concentration. In all, 52% would consider statin and fibrate
      together. Budgetary consideration influenced 6%. Northern Ireland general
      practitioners are reluctant to prescribe medication that is effective in the
      secondary prevention of vascular morbidity and mortality in high-risk patients.

PMID- 18319224
TI  - Isosorbide dinitrate spray as therapeutic strategy for treatment of chronic
      venous ulcers.
AB  - Venous ulcers are the most common form of leg ulcers, which induce lesion because
      of the loss of substances deposited on the damaged skin. Isosorbide dinitrate is
      a vasodilator with effects on both arteries and veins and induces opening of
      vascular layers. The objective is to study the effects of isosorbide dinitrate
      spray in patients with chronic venous ulcers. Forty-five patients of both sexes
      with chronic venous ulcers were randomized to receive isosorbide dinitrate or
      placebo sprays daily for 3 months. The ulcers were measured and clinical
      characteristics were taken every 15 days during the treatment. Patients treated
      with isosorbide dinitrate showed an improvement of the ulcerated area (71.29%)
      compared with patients treated with placebo (54.35%). The histopathological study
      indicated an increment in the number of hypertrophic and hyperplasic capillaries.
      Macroscopically, the isosorbide dinitrate-treatment showed the best results, but
      it was only during the first 6 weeks of treatment. Patients with chronic venous
      ulcer receiving isosorbide dinitrate spray showed improvement.

PMID- 18319225
TI  - The Tromped: a solution for flight-related deep vein thrombosis?
AB  - Flight-related deep vein thrombosis (DVT) is well recognized. Reduced venous
      return occurs during immobility. This alteration in venous hemodynamics may
      contribute to DVT development. A prototype design of an in-flight exercise device
      to stimulate ambulatory bloodflow while seated has been developed, consisting of
      a foot pedal attached to a base by a hinge mechanism. Four devices of differing
      resistance were evaluated. Calf muscle pump function was assessed by air
      plethysmography in 10 healthy volunteers. Ejection volume fraction and RVF were
      determined in the standing position (control values) and were compared with those
      achieved by depression of the 4 devices while seated. Similar EVF and RVF values
      were achieved by the control and 2 of the devices. Plantar flexion against a
      predetermined resistance can effectively activate the calf muscle pump while
      seated and may reduce the incidence of flight-related DVT.

PMID- 18319226
TI  - Lymphatic tissue transplant in lymphedema--a minimally invasive, outpatient,
      surgical method: a 10-year follow-up pilot study.
AB  - Lymphedema is mainly characterized by swelling, fibrosis, and non-pitting edema.
      The aim of this study was evaluation of the long-term (10 years) effects of
      autologous lymphatic tissue implant in lymphedema. Lymphatic tissue from 9
      patients (harvested form the same patient in areas not affected by lymphedema)
      was reimplanted into the affected limb, and these patients were followed for 10
      years. Lymph nodes were harvested at the neck, axillary, or inguinal space
      (contralateral limb). Results showed that limb volume was decreased in the
      treatment group vs. controls. In ultrasound, black, low density, lymphatic spaces
      were visible in 100% of patients at inclusion but in only 23% of these subjects
      at 10 years. Thus, this early report proposes a new, minimally invasive method to
      improve lymphedema. Studies in progress will indicate the role of lymphatic
      transplant in the management of lymphedema and the best indications for this
      method.

PMID- 18319227
TI  - Levo-propionyl-carnitine improves the effectiveness of supervised physical
      training on the absolute claudication distance in patients with intermittent
      claudication.
AB  - The mechanisms by which supervised physical training improves walking ability in
      patients with intermittent claudication (IC) are microcirculatory, rheological,
      and metabolic. The main mechanism of levo-propionylcarnitine (LPC) is metabolic;
      it increases the walking ability in claudicants, providing an additional energy
      to the ischemic muscle by an anaplerotic activity. Therefore, the current study
      was carried out to ascertain whether the combined treatment has a synergistic
      effect. The results confirm the effectiveness of supervised physical training in
      patients with IC, and we recommend the use of LPC during the exercise training
      program, at least in patients with severe claudication. Finally, underlining the
      similar mechanisms of physical training and LPC treatment, the study suggests
      that a cycle of LPC infusions could be advised in patients with severe
      claudication who cannot be included, for various reasons, in an exercise
      rehabilitation program.

PMID- 18319228
TI  - Intravenous port catheter embolization: mechanisms, clinical features, and
      management.
AB  - Venous catheters are important therapeutic devices for the administration of
      fluid and chemotherapeutic agents; however, their use may be associated with
      serious complications, such as catheter rupture and embolism. Most data on port
      catheter embolization consist of isolated case reports; only a few studies have
      examined a large number of patients with port catheter embolism. The purpose of
      this study was to identify the incidence of clinical symptoms in patients with
      catheter dislocation and to determine the role of catheter fragment localization
      in combination with the presenting symptoms. We conducted a retrospective
      analysis of patients admitted to Martin-Luther University Hospital Center from
      January 1994 to September 2005. In total, 41 patients with centrally dislocated
      catheter fragments were analyzed. Most catheter fragments were located in the
      pulmonary artery, superior vena cava, and right atrium. Of the patients in whom
      the catheter fragments were located in the right atrium, right ventricle, and the
      pulmonary artery, 7.3% presented cardiac symptoms. Catheter malfunction occurred
      in 39%. In 53.7%, catheter embolism was found incidentally. The embolized
      catheter fragments were retrieved by a goose-neck snare under fluoroscopy within
      24 hours after the diagnosis without any complications. The mean length of these
      fragments was 11.6 cm. Catheter embolism may go undiagnosed for a prolonged
      period and be found incidentally. In these patients, predominantly local symptoms
      occur; however, severe systemic clinical signs may develop. The risk of serious
      complications in asymptomatic catheter embolism is unknown. Catheter fragments
      should be removed to prevent further complications.

PMID- 18319229
TI  - Fernando Martorell (1906-1984): centenary of a pioneer in angiology.

PMID- 18319230
TI  - Diagnosis and management of subclavian vein thrombosis: three case reports and
      review of literature.
AB  - Axillosubclavian vein thrombosis is seen relatively infrequently in clinical
      practice when compared with lower limb deep-venous thrombosis; however, it is a
      condition that can result in significant morbidity if managed suboptimally. A
      multimodal treatment approach has been increasingly adopted with thrombolysis
      and/or thoracic outlet decompression being favored over anticoagulation alone,
      although the evidence base to support this approach is limited. In all, 3 cases
      are reported, which highlight numerous pertinent issues relating to the
      diagnostic and therapeutic options available.

PMID- 18319231
TI  - Dolichoectatic cervical arteries (carotid and vertebral arteries) heralded by
      recurrent cerebral ischemia: case illustration.
AB  - A case of a 61-year-old man with recurrent episodes of cerebral transient
      ischemic attacks is reported. The patient had a history of cigarette smoking,
      hypertension, hypercholesterolemia, and diabetes mellitus. Before these episodes,
      the patient had no clinical symptoms and signs of cerebral pathology. Brain
      magnetic resonance imaging revealed microvascular lesions in the white matter of
      the cerebral hemispheres. Digital subtraction arteriogram revealed the aortic
      arch dolichoic shape and course of the great vessels originating from it, whereas
      there were no pathological findings from the intracranial vessels. This study
      describes a case of the existence of distal dolichoectasia of the vertebral and
      carotid arteries without intracranial dolichoectasia. It seems that such a type
      of dolichoectasia does not influence the performance status of a patient, but
      when a critical point is crossed, patients suffer from cerebrovascular disease.

PMID- 18319232
TI  - Postaortic valve replacement bradycardia induced torsades de pointes.
AB  - The authors present an unusual case of torsades de pointes (Tdp) in an elderly
      woman with a history of aortic stenosis, status post aortic valve replacement.
      She was admitted for atrial fibrillation with a slow ventricular response. At the
      time of admission, the patient was asymptomatic and not taking any medications
      known to be associated with QT prolongation. During hospitalization, she
      developed episodes of Tdp without any provocable cause. This case highlights the
      occurrence of Tdp secondary to conduction disturbance caused by aortic valve
      surgery.

PMID- 18319233
TI  - Migration of an endovascular stent from superior vena cava to the right
      ventricular outflow tract in a patient with superior vena cava syndrome.
AB  - Migration of endovascular stents is a rare problem but can be fatal. We report an
      unusual case of an endovascular stent in the right ventricular outflow tract,
      which migrated from superior vena cava in a patient with superior vena cava
      syndrome.

PMID- 18319234
TI  - Coronary stenosis treated by percutaneous angioplasty in a patient with
      dermatomyositis.
AB  - A female patient suffering from dermatomyositis in whom symptoms of heart failure
      without angina is described. An impairment of left ventricular function and
      significant coronary lesions were diagnosed using noninvasive and invasive
      procedures. Coronary angioplasty with stent implantation was successfully applied
      to improve the quality of life and clinical symptoms.

PMID- 18319235
TI  - Hyperkalemia secondary to a postobstructive uropathy manifesting as complete
      heart block in a hypertensive patient receiving multiple atrioventricular nodal
      blocking agents.

PMID- 18319236
TI  - Nosocomial outbreak of vancomycin-resistant Enterococcus faecium in a paediatric
      unit at a Turkish university hospital.
AB  - BACKGROUND: Despite growing concern about vancomycin-resistant enterococci (VRE)
      as nosocomial pathogens, especially in the USA, they have been rarely isolated in
      Turkish hospitals. After initial description in 2001 of unrelated VRE isolates,
      we report now the molecular characterization of a nosocomial outbreak at the
      Akdeniz University Hospital, Antalya, Turkey. METHODS: VRE isolates were from
      either clinical or rectal swab specimens. Identification, susceptibility testing
      and molecular characterization were performed according to standard techniques.
      Virulence genes (encoding aggregation substance, gelatinase, cytolysin,
      enterococcal surface protein and hyaluronidase) were sought by PCR. RESULTS:
      Thirty-six VRE were isolated from 10 patients between June and October 2005 in
      the Department of Paediatrics. Six patients were only carriers, two had urinary
      tract infections and two had bloodstream infections. All isolates were
      Enterococcus faecium, of vanA genotype and belonged either to a main pulsotype
      (A) or to three minor pulsotypes (B, C and D). The epidemic strain A, found in
      eight patients, expressed high-level glycopeptide resistance (MIC of vancomycin
      256 mg/L and MIC of teicoplanin 64 mg/L) and was of multilocus sequence typing
      sequence type (ST) 31, whereas the minor strain D, found in two patients,
      expressed heterogeneous glycopeptide resistance (MIC of vancomycin 8 to 256 mg/L)
      and was ST18. Strains B and C were only found in single patients either with
      strain A or alone. The two epidemic strains A and D were esp gene-positive. Their
      vanA genes were located on transposons similar to Tn1546, except for deletion of
      the transposition genes and the presence of IS1542, inserted upstream of the vanA
      operon, and IS1216, inserted at the 3' end of the vanX gene. VRE outbreak was
      contained by early identification and implementation of measures for patient
      isolation and of stringent hand and environmental disinfection policies.
      CONCLUSIONS: This work underlines the emergence in Turkey of epidemic VRE clones
      that belong to the clonal complex-17 (CC-17) and that are esp-positive.

PMID- 18319237
TI  - Nosocomial bloodstream infections due to metallo-beta-lactamase-producing
      Pseudomonas aeruginosa.

PMID- 18319238
TI  - Large-scale mRNA expression profiling in the common ice plant, Mesembryanthemum
      crystallinum, performing C3 photosynthesis and Crassulacean acid metabolism
      (CAM).
AB  - The common ice plant (Mesembryanthemum crystallinum L.) has emerged as a useful
      model for molecular genetic studies of Crassulacean acid metabolism (CAM) because
      CAM can be induced in this species by water deficit or salinity stress. Non
      redundant sequence information from expressed sequence tag data was used to
      fabricate a custom oligonucleotide microarray to compare large-scale mRNA
      expression patterns in M. crystallinum plants conducting C(3) photosynthesis
      versus CAM. Samples were collected every 4 h over a 24 h time period at the start
      of the subjective second day from plants grown under constant light and
      temperature conditions in order to capture variation in mRNA expression due to
      salinity stress and circadian clock control. Of 8455 genes, a total of 2343 genes
      (approximately 28%) showed a significant change as judged by analysis of variance
      (ANOVA) in steady-state mRNA abundance at one or more time points over the 24 h
      period. Of these, 858 (10%) and 599 (7%) exhibited a greater than two-fold ratio
      (TFR) increase or decrease in mRNA abundance, respectively. Functional
      categorization of these TFR genes revealed that many genes encoding products that
      function in CAM-related C(4) acid carboxylation/decarboxylation,
      glycolysis/gluconeogenesis, polysaccharide, polyol, and starch
      biosynthesis/degradation, protein degradation, transcriptional activation,
      signalling, stress response, and transport facilitation, and novel, unclassified
      proteins exhibited stress-induced increases in mRNA abundance. In contrast, salt
      stress resulted in a significant decrease in transcript abundance for genes
      encoding photosynthetic functions, protein synthesis, and cellular biogenesis
      functions. Many genes with CAM-related functions exhibited phase shifts in their
      putative circadian expression patterns following CAM induction. This report
      establishes an extensive catalogue of gene expression patterns for future
      investigations aimed at understanding the complex, transcriptional hierarchies
      that govern CAM-specific expression patterns. A novel graph-theoretic approach
      called 'Max Clique Builder' is introduced that identifies and organizes sets of
      coordinately regulated genes, such as those encoding subunits of the vacuolar
      H(+)-ATPase complex, into tighter functionally related clusters with more similar
      expression patterns compared with standard hierarchical clustering methods.

PMID- 18319239
TI  - A new species of Phyllopsora (Lecanorales, lichen-forming Ascomycota) from
      Dominican amber, with remarks on the fossil history of lichens.
AB  - Phyllopsora dominicanus sp. nov. (Bacidiaceae, Lecanorales, lichen-forming
      Ascomycota) is described and illustrated from Dominican amber. The diagnostic
      features of the lichen include a minute subfolious thallus of lacinulate,
      ascending squamules, a well-developed upper cortex, and a net-like pseudocortex
      on the lower surface. The algal symbionts are unicellular green algae, forming a
      distinct layer immediately below the upper cortex. The fossil demonstrates that
      distinguishing features of Phyllopsora have remained unchanged for tens of
      millions of years. The fossil also provides the first detailed views of mycobiont
      photobiont contacts in Tertiary green algal lichens. The mycobiont hyphae formed
      apical and intercalary appressoria by pressing closely against the photobiont
      cells. This indicates that a conserved maintenance of structure is also seen in
      the fine details of the fungal-algal interface.

PMID- 18319240
TI  - Genetic engineering of rice capable of synthesizing fructans and enhancing
      chilling tolerance.
AB  - Fructans are water-soluble fructose oligomers and polymers that are based on
      sucrose, and have been implicated in protecting plants against water stress. Rice
      (Oryza sativa L.) is highly sensitive to chilling temperatures, and is not able
      to synthesize fructans. Two wheat fructan-synthesizing enzymes, sucrose:sucrose 1
      fructosyltransferase, encoded by wft2, or sucrose:fructan 6-fructosyltransferase,
      encoded by wft1, were introduced into rice plants, and rice transformants that
      accumulate fructans were successfully obtained. The mature leaf blades of
      transgenic rice lines with wft2 or wft1 accumulated 16.2 mg g(-1) FW of oligo-
      and polysaccharides mainly composed of inulin oligomers of more than DP7, and 3.7
      mg g(-1) FW of oligo- and polysaccharides, mainly composed of phlein oligomers of
      more than DP15, respectively. The transgenic rice seedlings with wft2 accumulated
      significantly higher concentrations of oligo- and polysaccharides than non
      transgenic rice seedlings, and exhibited enhanced chilling tolerance. The oligo-
      and polysaccharide concentrations of seedlings expressing wft1 were obviously
      lower than those of lines expressing wft2, and no correlation between oligo- and
      polysaccharide concentrations and chilling tolerance was detected in wft1
      expressing rice lines. The results suggest that transgenic rice lines expressing
      wheat-derived fructosyltransferase genes accumulated large amounts of fructans in
      mature leaf blades and exhibited enhanced chilling tolerance at the seedling
      stage. This is the first report owing that fructan accumulation enhanced
      tolerance to non-freezing low temperatures.

PMID- 18319241
TI  - The remarkable chloroplast genome of dinoflagellates.
AB  - Dinoflagellates are an economically and ecologically important eukaryotic algal
      group. The organization of their chloroplast genome appears to be radically
      different from that in plants and other algae. The gene content has been
      dramatically reduced in dinoflagellates, with the large-scale transfer of genes
      to the nucleus. Most of the remaining genes encode subunits of Photosystems I and
      II, the cytochrome b(6)f complex, and ATP synthase, as well as rRNAs and a few
      tRNAs. Whereas conventional chloroplast genomes have all their genes physically
      linked on one molecule, dinoflagellate chloroplast genes are located on small
      plasmids, termed 'minicircles'. Each minicircle has at most a few genes, and a
      distinguishable 'core' region. Genes are always in the same orientation with
      respect to the core region. There are also non-coding minicircles, including
      aberrant forms of minicircles apparently derived from other minicircles by
      rearrangement. The evidence that the minicircles are located in the chloroplast
      and that there is no conventional chloroplast genome in addition to the
      minicircles is discussed. Transcription of minicircles is probably initiated
      close to the core, generating transcripts corresponding to an almost entire
      minicircle. The transcripts are then cleaved to molecules corresponding to
      individual genes. Post-transcriptional modifications include editing and addition
      of a polyU tail. It is discussed why these particular genes have been retained in
      the dinoflagellate chloroplast, together with the possibility that the
      chloroplast supplies fMet-tRNA to the mitochondrion.

PMID- 18319242
TI  - Neurotoxicological evaluation of long-term lanthanum chloride exposure in rats.
AB  - With their widespread application in industry, agriculture, medicine, and daily
      life, rare earth elements (REEs) are widely used in various fields and eventually
      accumulated in human body. Therefore, understanding the effects of REEs on health
      has become more and more important. In this work, the neurotoxicity of lanthanum
      (La) was evaluated. Wistar rats were exposed to lanthanum chloride through oral
      administration at 0, 0.1, 2, and 40 mg/kg doses from gestation day 0 through 6
      months of age. Experiments were carried out to reveal the effects of La exposure
      on brain functions from four aspects including behavioral performance, [Ca2+](i)
      level and the activity of Ca2+-ATPase (adenosine triphosphatase) in hippocampal
      cells, oxidative stress, and Nissl staining. Adverse effects were observed in 2
      and 40 mg/kg dose groups and increased with dose. Morris water maze test showed
      that La exposure at 2 and 40 mg/kg could significantly impair the behavioral
      performance. (The preference for the target quadrant decreased by 16.6% and 19.4%
      versus control, respectively.) The neurotoxicological consequences demonstrated
      that the alteration in homeostasis of [Ca2+](i)/Ca2+-ATPase (the ratio of
      [Ca2+](i) vs. Ca2+-ATPase activity increased by 44% in rats of 40 mg/kg group),
      the inhibition to activities of antioxidant enzymes, and the subsequent cell
      damage (18% and 23% cell loss in CA3 subregion of rats in 2 and 40 mg/kg group,
      respectively) might be involved in the neurological adverse effects of REEs
      exposure.

PMID- 18319243
TI  - Na+/H+ exchanger-1 inhibitors reduce neuronal excitability and alter na+ channel
      inactivation properties in rat primary sensory neurons.
AB  - Inhibitors of the Na+/H+ exchanger isoform 1 (NHE-1) have been associated with
      peripheral neuropathy in rats and dogs. Recent studies suggest that NHE-1 plays
      an important role in mediating neuronal excitability. To investigate potential
      NHE-1-mediated mechanisms contributing to neuronal toxicity, we studied the
      effects of NHE-1 inhibitors on nerve and dorsal root ganglion (DRG) neurons
      isolated from the adult rat. Compound action potentials (CAPs) were recorded from
      electrically stimulated sections of isolated sciatic nerve/DRG/root preparations.
      Whole-cell patch-clamp technique was used to record fast and slow voltage
      dependent Na+ currents from dissociated DRG neurons (29-41 microm). Exposures to
      1 and 10 microM of a selective NHE-1 inhibitor reduced the amplitude of the CAP
      recorded from the dorsal root by 33% and 58%, respectively (p < 0.05). The
      compound had no effect on CAPs recorded from the ventral root. Perfusion of
      dissociated DRG neurons with NHE-1 inhibitors at 10 and 100 microM shifted
      voltage-dependent inactivation curves of fast Na+ current by as much as 11 mV (p
      < 0.001) in the hyperpolarizing direction. No shift was observed in slow Na+
      currents. No statistically significant drug effects were observed on voltage
      dependent activation or recovery from inactivation of either fast or slow Na+
      currents. These results suggest that NHE-1 inhibitors may reduce peripheral
      neuronal excitability by shifting fast Na+ channels into the inactivated state
      under physiological conditions. Such effects may underlie peripheral neuropathies
      reported in rats and dogs with NHE-1 inhibitors.

PMID- 18319244
TI  - A mixed branch length model of heterotachy improves phylogenetic accuracy.
AB  - Evolutionary relationships are typically inferred from molecular sequence data
      using a statistical model of the evolutionary process. When the model accurately
      reflects the underlying process, probabilistic phylogenetic methods recover the
      correct relationships with high accuracy. There is ample evidence, however, that
      models commonly used today do not adequately reflect real-world evolutionary
      dynamics. Virtually all contemporary models assume that relatively fast-evolving
      sites are fast across the entire tree, whereas slower sites always evolve at
      relatively slower rates. Many molecular sequences, however, exhibit site-specific
      changes in evolutionary rates, called "heterotachy." Here we examine the accuracy
      of 2 phylogenetic methods for incorporating heterotachy, the mixed branch length
      model--which incorporates site-specific rate changes by summing likelihoods over
      multiple sets of branch lengths on the same tree--and the covarion model, which
      uses a hidden Markov process to allow sites to switch between variable and
      invariable as they evolve. Under a variety of simple heterogeneous simulation
      conditions, the mixed model was dramatically more accurate than homotachous
      models, which were subject to topological biases as well as biases in branch
      length estimates. When data were simulated with strong versions of the types of
      heterotachy observed in real molecular sequences, the mixed branch length model
      was more accurate than homotachous techniques. Analyses of empirical data sets
      confirmed that the mixed branch length model can improve phylogenetic accuracy
      under conditions that cause homotachous models to fail. In contrast, the covarion
      model did not improve phylogenetic accuracy compared with homotachous models and
      was sometimes substantially less accurate. We conclude that a mixed branch length
      approach, although not the solution to all phylogenetic errors, is a valuable
      strategy for improving the accuracy of inferred trees.

PMID- 18319245
TI  - The hominoid-specific oncogene TBC1D3 activates Ras and modulates epidermal
      growth factor receptor signaling and trafficking.
AB  - Hominoid- and human-specific genes may have evolved to modulate signaling
      pathways of a higher order of complexity. TBC1D3 is a hominoid-specific oncogene
      encoded by a cluster of eight paralogs on chromosome 17. Initial work indicates
      that TBC1D3 is widely expressed in human tissues ( Hodzic, D., Kong, C.,
      Wainszelbaum, M. J., Charron, A. J., Su, X., and Stahl, P. D. (2006) Genomics 88,
      731-736 ). In this study, we show that TBC1D3 expression has a powerful effect on
      cell proliferation that is further enhanced by epidermal growth factor (EGF) in
      both human and mouse cell lines. EGF activation of the Erk and protein kinase
      B/Akt pathways is enhanced, both in amplitude and duration, by TBC1D3 expression,
      whereas RNA interference silencing of TBC1D3 suppresses the activation. Light
      microscopy and Western blot experiments demonstrate that increased signaling in
      response to EGF is coupled with a significant delay in EGF receptor (EGFR)
      trafficking and degradation, which significantly extends the life span of EGFR.
      Moreover, TBC1D3 suppresses polyubiquitination of the EGFR and the recruitment of
      c-Cbl. Using the Ras binding domain of Raf1 to monitor GTP-Ras we show that
      TBC1D3 expression enhances Ras activation in quiescent cells, which is further
      increased by EGF treatment. We speculate that TBC1D3 may alter Ras GTP loading.
      We conclude that the expression of TBC1D3 generates a delay in EGFR degradation,
      a decrease in ubiquitination, and a failure to recruit adapter proteins that
      ultimately dysregulate EGFR signal transduction and enhance cell proliferation.
      Altered growth factor receptor trafficking and GTP-Ras turnover may be sites
      where recently evolved genes such as TBC1D3 selectively modulate signaling in
      hominoids and humans.

PMID- 18319246
TI  - Activation of D-tyrosine by Bacillus stearothermophilus tyrosyl-tRNA synthetase:
      2. Cooperative binding of ATP is limited to the initial turnover of the enzyme.
AB  - The activation of D-tyrosine by tyrosyl-tRNA synthetase has been investigated
      using single and multiple turnover kinetic methods. In the presence of saturating
      concentrations of D-tyrosine, the activation reaction displays sigmoidal kinetics
      with respect to ATP concentration under single turnover conditions. In contrast,
      when the kinetics for the activation reaction are monitored using a steady-state
      (multiple turnover) pyrophosphate exchange assay, Michaelis-Menten kinetics are
      observed. Previous investigations indicated that activation of l-tyrosine by the
      K233A variant of Bacillus stearothermophilus tyrosyl-tRNA synthetase displays
      sigmoidal kinetics similar to those observed for activation of d-tyrosine by the
      wild-type enzyme. Kinetic analyses indicate that the sigmoidal behavior of the d
      tyrosine activation reaction is not enhanced when Lys-233 is replaced by alanine.
      This supports the hypothesis that the mechanistic basis for the sigmoidal
      behavior is the same for both d-tyrosine activation by wild-type tyrosyl-tRNA
      synthetase and activation of l-tyrosine by the K233A variant. The observed
      sigmoidal behavior presents a paradox, as tyrosyl-tRNA synthetase displays an
      extreme form of negative cooperativity, known as "half-of-the-sites reactivity,"
      with respect to tyrosine binding and tyrosyl-adenylate formation. We propose that
      the binding of D-tyrosine weakens the affinity with which ATP binds to the
      functional subunit in tyrosyl-tRNA synthetase. This allows ATP to bind initially
      to the nonfunctional subunit, inducing a conformational change in the enzyme that
      enhances the affinity of the functional subunit for ATP. The observation that
      sigmoidal kinetics are observed only under single turnover conditions suggests
      that this conformational change is stable over multiple rounds of catalysis.

PMID- 18319247
TI  - Activation of D-tyrosine by Bacillus stearothermophilus tyrosyl-tRNA synthetase:
      1. Pre-steady-state kinetic analysis reveals the mechanistic basis for the
      recognition of D-tyrosine.
AB  - Tyrosyl-tRNA synthetase (TyrRS) is able to catalyze the transfer of both l- and d
      tyrosine to the 3' end of tRNA(Tyr). Activation of either stereoisomer by ATP
      results in formation of an enzyme-bound tyrosyl-adenylate intermediate and is
      accompanied by a blue shift in the intrinsic fluorescence of the protein. Single
      turnover kinetics for the aminoacylation of tRNA(Tyr) by D-tyrosine were
      monitored using stopped-flow fluorescence spectroscopy. Bacillus
      stearothermophilus tyrosyl-tRNA synthetase binds d-tyrosine with an 8.5-fold
      lower affinity than that of l-tyrosine (K (D-Tyr)(d) = 102 microm) and exhibits a
      3-fold decrease in the forward rate constant for the activation reaction (k (D
      Tyr)(3) = 13 s(-1)). Furthermore, as is the case for l-tyrosine, tyrosyl-tRNA
      synthetase exhibits "half-of-the-sites" reactivity with respect to the binding
      and activation of D-tyrosine. Surprisingly, pyrophosphate binds to the TyrRS.d
      Tyr-AMP intermediate with a 14-fold higher affinity than it binds to the TyrRS.l
      Tyr-AMP intermediate (K (PPi)(d) = 0.043 for TyrRS.d-Tyr-AMP.PP(i)). tRNA(Tyr)
      binds with a slightly (2.3-fold) lower affinity to the TyrRS.d-Tyr-AMP
      intermediate than it does to the TyrRS.l-Tyr-AMP intermediate. The observation
      that the K (Tyr)(d) and k(3) values are similar for l- and d-tyrosine suggests
      that their side chains bind to tyrosyl-tRNA synthetase in similar orientations
      and that at least one of the carboxylate oxygen atoms in d-tyrosine is properly
      positioned for attack on the alpha-phosphate of ATP.

PMID- 18319248
TI  - A biotin interference assay highlights two different asymmetric interaction
      profiles for lambda integrase arm-type binding sites in integrative versus
      excisive recombination.
AB  - The site-specific recombinase integrase encoded by bacteriophage lambda promotes
      integration and excision of the viral chromosome into and out of its Escherichia
      coli host chromosome through a Holliday junction recombination intermediate. This
      intermediate contains an integrase tetramer bound via its catalytic carboxyl
      terminal domains to the four "core-type" sites of the Holliday junction DNA and
      via its amino-terminal domains to distal "arm-type" sites. The two classes of
      integrase binding sites are brought into close proximity by an ensemble of
      accessory proteins that bind and bend the intervening DNA. We have used a biotin
      interference assay that probes the requirement for major groove protein binding
      at specified DNA loci in conjunction with DNA protection, gel mobility shift, and
      genetic experiments to test several predictions of the models derived from the x
      ray crystal structures of minimized and symmetrized surrogates of recombination
      intermediates lacking the accessory proteins and their cognate DNA targets. Our
      data do not support the predictions of "non-canonical" DNA targets for the N
      domain of integrase, and they indicate that the complexes used for x-ray
      crystallography are more appropriate for modeling excisive rather than
      integrative recombination intermediates. We suggest that the difference in the
      asymmetric interaction profiles of the N-domains and arm-type sites in
      integrative versus excisive recombinogenic complexes reflects the regulation of
      recombination, whereas the asymmetry of these patterns within each reaction
      contributes to directionality.

PMID- 18319249
TI  - Identification of regulatory factor X as a novel mismatch repair stimulatory
      factor.
AB  - This report describes the identification and purification of a novel mismatch
      repair stimulatory factor from HeLa cell extracts. This activity copurifies with
      a proliferating cell nuclear antigen-dependent 5 ' --> 3 ' DNA excision activity
      during several purification steps but is resolved from the excision activity
      during gel filtration chromatography using Sephacryl S-300. After purification to
      near homogeneity, the stimulatory factor is associated with three polypeptides
      with apparent molecular masses of 68, 36, and 30 kDa. Peptide sequencing analysis
      by tandem mass spectrometry identified the stimulatory factor as the
      heterotrimeric regulatory factor X (RFX) complex, which regulates transcription
      of the class II major histocompatibility complex by facilitating histone
      acetylation and is defective in the human hereditary immunodeficiency syndrome
      called bare lymphocyte syndrome. This conclusion was confirmed by the facts that
      purified recombinant RFX stimulates mismatch repair in an in vitro reconstituted
      mismatch repair system and that depletion of RFX from nuclear extracts or RFX
      knockdown in cells reduces mismatch repair activity. As expected, RFX knockdown
      cells display instability in microsatellite sequences. The possible role of RFX
      in human MMR repair is discussed.

PMID- 18319250
TI  - Binding of yeast frataxin to the scaffold for Fe-S cluster biogenesis, Isu.
AB  - Friedreich ataxia is caused by reduced activity of frataxin, a conserved iron
      binding protein of the mitochondrial matrix, thought to supply iron for formation
      of Fe-S clusters on the scaffold protein Isu. Frataxin binds Isu in an iron
      dependent manner in vitro. However, the biological relevance of this interaction
      and whether in vivo the interaction between frataxin and Isu is mediated by
      adaptor proteins is a matter of debate. Here, we report that alterations of
      conserved, surface-exposed residues of yeast frataxin, which have deleterious
      effects on cell growth, impair Fe-S cluster biogenesis and interaction with Isu
      while altering neither iron binding nor oligomerization. Our results support the
      idea that the surface of the beta-sheet, adjacent to the acidic, iron binding
      ridge, is important for interaction of Yfh1 with the Fe-S cluster scaffold and
      point to a critical role for frataxin in Fe-S cluster biogenesis.

PMID- 18319251
TI  - Activation of cyclic AMP Signaling in Ae2-deficient mouse fibroblasts.
AB  - Anion exchanger 2 (AE2, SLC4A2) is a ubiquitously expressed membrane solute
      carrier that regulates intracellular pH (pH(i)) by exchanging cytosolic
      bicarbonate for extracellular chloride. We used fibroblasts from Ae2-deficient
      (Ae2(a,b)(-/-)) mice to study the effects of an alkaline shift in resting
      intracellular pH (pH(i)) on the activation of cAMP signaling and gene expression.
      Ae2(a,b)(-/-) fibroblasts show increased pH(i) (by 0.22 +/- 0.03 unit) compared
      with wild type cells at extracellular pH (pH(o)) 7.4 and 37 degrees C. This shift
      in resting pH(i) is associated with an up-regulation of bicarbonate-activated
      soluble adenylyl cyclase expression, increased cAMP production, Creb
      phosphorylation, inducible cAMP early repressor 1 mRNA expression, and impaired
      activation of c-Fos transcription by forskolin. These results highlight the
      importance of bicarbonate transport via Ae2 in maintaining pH(i) homeostasis in
      cultured mouse fibroblasts and unveil the role of cAMP in the cellular response
      to chronic alkalization, which putatively includes an inducible cAMP early
      repressor 1-mediated attenuation of phosphorylated Creb activity.

PMID- 18319252
TI  - Constitutive activity of the cannabinoid CB1 receptor regulates the function of
      co-expressed Mu opioid receptors.
AB  - The human mu opioid receptor was expressed stably in Flp-In T-REx HEK293 cells.
      Occupancy by the agonist DAMGO (Tyr-d-Ala-Gly-N-methyl-Phe-Gly-ol) resulted in
      phosphorylation of the ERK1/2 MAP kinases, which was blocked by the opioid
      antagonist naloxone but not the cannabinoid CB1 receptor inverse agonist
      SR141716A. Expression of the human cannabinoid CB1 receptor in these cells from
      the inducible Flp-In T-REx locus did not alter expression levels of the mu opioid
      receptor. This allowed the cannabinoid CB1 agonist WIN55212-2 to stimulate ERK1/2
      phosphorylation but resulted in a large reduction in the capacity of DAMGO to
      activate these kinases. Although lacking affinity for the mu opioid receptor, co
      addition of SR141716A caused recovery of the effectiveness of DAMGO. In contrast
      co-addition of the CB1 receptor neutral antagonist O-2050 did not. Induction of
      the CB1 receptor also resulted in an increase of basal [(35)S]guanosine 5'-3-O
      (thio)triphosphate (GTPgammaS) binding and thereby a greatly reduced capacity of
      DAMGO to further stimulate [(35)S]GTPgammaS binding. CB1 inverse agonists
      attenuated basal [(35)S]GTPgammaS binding and restored the capacity of DAMGO to
      stimulate. Flp-In T-REx HEK293 cells were generated, which express the human mu
      opioid receptor constitutively and harbor a modified D163N cannabinoid CB1
      receptor that lacks constitutive activity. Induction of expression of the
      modified cannabinoid CB1 receptor did not limit DAMGO-mediated ERK1/2 MAP kinase
      phosphorylation and did not allow SR141716A to enhance the function of DAMGO.
      These data indicate that it is the constitutive activity inherent in the
      cannabinoid CB1 receptor that reduces the capacity of co-expressed mu opioid
      receptor to function.

PMID- 18319253
TI  - Cyclooxygenase-2 up-regulates CCR7 via EP2/EP4 receptor signaling pathways to
      enhance lymphatic invasion of breast cancer cells.
AB  - Recent studies demonstrate that cyclooxygenase-2 (COX-2) expression is frequently
      associated with lymph node metastasis. However, the mechanism by which COX-2
      increases the invasion of cancer cells to lymph node is unclear. CCR7 is a
      chemokine receptor that plays important roles in the mediation of migration of
      leukocytes and dendritic cells toward lymphatic endothelial cells (LECs) that
      express receptor ligand CCL21. We found that treatment of prostaglandin E(2) or
      ectopic expression of COX-2 in MCF-7 cells up-regulated CCR7 expression. On the
      contrary, knockdown of COX-2 by small hairpin RNA reduced CCR7 in COX-2
      overexpressing MDA-MB-231 cells. Interaction of CCR7 and CCL21 was important for
      the migration of breast cancer cells toward LECs because antibodies against these
      two molecules inhibited the migration. We also found that COX-2 increased CCR7
      expression via the EP2 and EP4 receptor in breast cancer cells. EP2 and EP4
      agonists stimulated CCR7 in MCF-7 cells, whereas antagonists or small hairpin RNA
      of EP2 and EP4 attenuated CCR7 in MDA-MB-231 cells. Protein kinase A and AKT
      kinase were involved in COX-2-induced CCR7. Pathological analysis demonstrated
      that COX-2 overexpression was associated with CCR7, EP2, and EP4 expressions in
      breast tumor tissues. In addition, CCR7 expression in COX-2-overexpressing tumors
      was significantly correlated with lymph node metastasis. Collectively, we suggest
      that CCR7 is a down-stream target for COX-2 to enhance the migration of breast
      cancer cells toward LECs and to promote lymphatic invasion.

PMID- 18319254
TI  - Characterization of human SLC4A10 as an electroneutral Na/HCO3 cotransporter
      (NBCn2) with Cl- self-exchange activity.
AB  - The SLC4A10 gene product, commonly known as NCBE, is highly expressed in rodent
      brain and has been characterized by others as a Na(+)-driven Cl-HCO(3) exchanger.
      However, some of the earlier data are not consistent with Na(+)-driven Cl-HCO(3)
      exchange activity. In the present study, northern blot analysis showed that, also
      in humans, NCBE transcripts are predominantly expressed in brain. In some human
      NCBE transcripts, splice cassettes A and/or B, originally reported in rats and
      mice, are spliced out. In brain cDNA, we found evidence of a unique partial
      splice of cassette B that is predicted to produce an NCBE protein with a novel C
      terminus containing a protein kinase C phosphorylation site. We used pH-sensitive
      microelectrodes to study the molecular physiology of human NCBE expressed in
      Xenopus oocytes. In agreement with others we found that NCBE mediates the 4,4'
      diisothiocyanato-stilbene-2,2'-disulfonic acid-sensitive, Na(+)-dependent
      transport of HCO(3)(-). For the first time, we demonstrated that this transport
      process is electroneutral. Using Cl(-)-sensitive microelectrodes positioned at
      the oocyte surface, we found that, unlike both human and squid Na(+)-driven Cl
      HCO(3) exchangers, human NCBE does not normally couple the net influx of HCO(3)(
      ) to a net efflux of Cl(-). Moreover we found that that the (36)Cl efflux from
      NCBE-expressing oocytes, interpreted by others to be coupled to the influx of
      Na(+) and HCO(3)(-), actually represents a CO(2)/HCO(3)(-)-stimulated Cl(-) self
      exchange not coupled to either Na(+) or net HCO(3)(-) transport. We propose to
      rename NCBE as the second electroneutral Na/HCO(3) cotransporter, NBCn2.

PMID- 18319255
TI  - Profiling microRNA expression in hepatocellular carcinoma reveals microRNA-224 up
      regulation and apoptosis inhibitor-5 as a microRNA-224-specific target.
AB  - Like other cancers, aberrant gene regulation features significantly in
      hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) were recently found to
      regulate gene expression at the post-transcriptional/translational levels. The
      expression profiles of 157 miRNAs were examined in 19 HCC patients, and 19 up
      regulated and 3 down-regulated miRNAs were found to be associated with HCC.
      Putative gene targets of these 22 miRNAs were predicted in silico and were
      significantly enriched in 34 biological pathways, most of which are frequently
      dysregulated during carcinogenesis. Further characterization of microRNA-224 (miR
      224), the most significantly up-regulated miRNA in HCC patients, revealed that
      miR-224 increases apoptotic cell death as well as proliferation and targets
      apoptosis inhibitor-5 (API-5) to inhibit API-5 transcript expression.
      Significantly, miR-224 expression was found to be inversely correlated with API-5
      expression in HCC patients (p < 0.05). Hence, our findings define a true in vivo
      target of miR-224 and reaffirm the important role of miRNAs in the dysregulation
      of cellular processes that may ultimately lead to tumorigenesis.

PMID- 18319256
TI  - The mechanism of cystic fibrosis transmembrane conductance regulator
      transcriptional repression during the unfolded protein response.
AB  - The unfolded protein response (UPR) aids cellular recovery by increasing the
      capacity and decreasing the protein load of the endoplasmic reticulum (ER).
      Although the main pathways of the UPR are known, the mechanisms of UPR-associated
      transcriptional repression have not been explored in mammalian cells. Previous
      studies indicate that endogenous cystic fibrosis transmembrane conductance
      regulator (CFTR) mRNA levels and protein maturation efficiency decrease when the
      UPR is activated. In the present study, we demonstrate that inhibition of CFTR
      expression under ER stress leads to reduced cAMP-activated chloride secretion in
      epithelial monolayers, an indication of diminished CFTR function. Moreover, ER
      stress and the UPR obliterate endogenous DeltaF508 CFTR mRNA expression in CFPAC
      1 cells without affecting recombinant DeltaF508 CFTR mRNA levels or mRNA half
      life. These results emphasize that transcriptional repression of CFTR under ER
      stress, in concert with decreased CFTR maturation efficiency, leads to diminished
      function. Using human CFTR promoter reporter constructs, we confined the ER
      stress-associated CFTR transcriptional repression to the minimal promoter.
      Chromatin immunoprecipitation assays established the binding of the UPR-activated
      ATF6 transcription factor to this region during ER stress, which links the
      repression to the UPR. Methylation-specific PCR (MSP) revealed hypermethylation
      of CpG sites inside and in the vicinity of the MAZ transcription factor binding
      region of CFTR, demonstrating methylation-dependent repression. Using
      pharmacological inhibitors, we show that both DNA methylation and histone
      deacetylation contribute to CFTR transcriptional inhibition. These studies
      provide novel insight into the mechanism of gene repression during the mammalian
      UPR.

PMID- 18319257
TI  - Highly conserved asparagine 82 controls the interaction of Na+ with the sodium
      coupled neutral amino acid transporter SNAT2.
AB  - The neutral amino acid transporter 2 (SNAT2), which belongs to the SLC38 family
      of solute transporters, couples the transport of amino acid to the cotransport of
      one Na(+) ion into the cell. Several polar amino acids are highly conserved
      within the SLC38 family. Here, we mutated three of these conserved amino acids,
      Asn(82) in the predicted transmembrane domain 1 (TMD1), Tyr(337) in TMD7, and
      Arg(374) in TMD8; and we studied the functional consequences of these
      modifications. The mutation of N82A virtually eliminated the alanine-induced
      transport current, as well as amino acid uptake by SNAT2. In contrast, the
      mutations Y337A and R374Q did not abolish amino acid transport. The K(m) of SNAT2
      for its interaction with Na(+), K(Na(+)), was dramatically reduced by the N82A
      mutation, whereas the more conservative mutation N82S resulted in a K(Na(+)) that
      was in between SNAT2(N82A) and SNAT2(WT). These results were interpreted as a
      reduction of Na(+) affinity caused by the Asn(82) mutations, suggesting that
      these mutations interfere with the interaction of SNAT2 with the sodium ion. As a
      consequence of this dramatic reduction in Na(+) affinity, the apparent K(m) of
      SNAT2(N82A) for alanine was increased 27-fold compared with that of SNAT2(WT).
      Our results demonstrate a direct or indirect involvement of Asn(82) in Na(+)
      coordination by SNAT2. Therefore, we predict that TMD1 is crucial for the
      function of SLC38 transporters and that of related families.

PMID- 18319258
TI  - Class-specific regulation of pro-inflammatory genes by MyD88 pathways and
      IkappaBzeta.
AB  - Toll-like receptors trigger the induction of primary response genes via MyD88
      mediated activation of NF-kappaB and other transcription factors. These factors
      then act in concert with primary response gene products to induce secondary
      response genes. Although the MyD88 pathway is important for the expression of
      both primary and secondary response genes, we show that the recruitment of NF
      kappaB, RNA polymerase, and the TATA-binding protein is MyD88-dependent only at
      secondary response genes. This selective dependence correlates with the fact that
      MyD88 is required for nucleosome remodeling and histone H3K4 trimethylation at
      secondary response promoters, whereas rapidly induced primary response promoters
      are assembled into poised MyD88-independent chromatin structures. At a subset of
      secondary response promoters, IkappaBzeta was identified as a selective regulator
      of H3K4 trimethylation and preinitiation complex assembly after nucleosome
      remodeling. These mechanistic distinctions advance our understanding of the
      diverse molecular cascades that underlie the differential regulation of pro
      inflammatory genes.

PMID- 18319259
TI  - Coordination of growth and endoplasmic reticulum stress signaling by regulator of
      calcineurin 1 (RCAN1), a novel ATF6-inducible gene.
AB  - Exposing cells to conditions that modulate growth can impair endoplasmic
      reticulum (ER) protein folding, leading to ER stress and activation of the
      transcription factor, ATF6. ATF6 binds to ER stress response elements in target
      genes, inducing expression of proteins that enhance the ER protein folding
      capacity, which helps overcome the stress and foster survival. To examine the
      mechanism of ATF6-mediated survival in vivo, we developed a transgenic mouse
      model that expresses a novel conditionally activated form of ATF6. We previously
      showed that activating ATF6 protected the hearts of ATF6 transgenic mice from ER
      stresses. In the present study, transcript profiling identified modulatory
      calcineurin interacting protein-1 (MCIP1), also known as regulator of calcineurin
      1 (RCAN1), as a novel ATF6-inducible gene that encodes a known regulator of
      calcineurin/nuclear factor of activated T cells (NFAT)-mediated growth and
      development in many tissues. The ability of ATF6 to induce RCAN1 in vivo was
      replicated in cultured cardiac myocytes, where adenoviral (AdV)-mediated
      overexpression of activated ATF6 induced the RCAN1 promoter, up-regulated RCAN1
      mRNA, inhibited calcineurin phosphatase activity, and exerted a striking growth
      modulating effect that was inhibited by RCAN1-targeted small interfering RNA.
      These results demonstrate that RCAN1 is a novel ATF6 target gene that may
      coordinate growth and ER stress signaling pathways. By modulating growth, RCAN1
      may reduce the need for ER protein folding, thus helping to overcome the stress
      and enhance survival. Moreover, these results suggest that RCAN1 may also be a
      novel integrator of growth and ER stress signaling in many other tissues that
      depend on calcineurin/NFAT signaling for optimal growth and development.

PMID- 18319260
TI  - GLI2-specific transcriptional activation of the bone morphogenetic
      protein/activin antagonist follistatin in human epidermal cells.
AB  - Hedgehog (HH) signaling in the epidermis is primarily mediated by the zinc finger
      transcription factors GLI1 and GLI2. Exquisite regulation of HH/GLI signaling is
      crucial for proper specification of the epidermal lineage and development of its
      derivatives, whereas dysregulation of HH/GLI signaling disrupts tissue
      homeostasis and causes basal cell carcinoma (BCC). Similarly, bone morphogenetic
      proteins (BMPs) and activins have been described as key signaling factors in the
      complex regulation of epidermal fate decisions, although their precise interplay
      with HH/GLI is largely elusive. Here we show that, in human epidermal cells,
      expression of the activin/BMP antagonist follistatin (FST) is predominantly up
      regulated by the HH effector GLI2. Consistently, we found strong FST expression
      in the outer root sheath of human hair follicles and BCC. Detailed promoter
      analysis showed that two sequences with homology to the GLI consensus binding
      site are required for GLI2-mediated activation. Interestingly, activation of the
      FST promoter is highly GLI2-specific, because neither GLI1 nor GLI3 can
      significantly increase FST transcription. GLI2 specificity requires the presence
      of a 518-bp fragment in the proximal FST promoter region. On the protein level,
      sequences C-terminal to the zinc finger are responsible for GLI2-specific
      activation of FST transcription, pointing to the existence of GLI-interacting
      cofactors that modulate GLI target specificity. Our results reveal a key role of
      GLI2 in activation of the activin/BMP antagonist FST in response to HH signaling
      and provide new evidence for a regulatory interaction between HH and activin/BMP
      signaling in hair follicle development and BCC.

PMID- 18319261
TI  - Direct interaction between SET8 and proliferating cell nuclear antigen couples H4
      K20 methylation with DNA replication.
AB  - Chromatin endowed by histone modifications governs chromatin structure, which in
      turn represents a means to regulate cellular processes, including transcription
      and heterochromatin formation. Recent evidence revealed a plethora of enzymes
      that catalyze specific histone modifications for epigenetic maintenance, and
      dysregulation of which contributes to tumorigenesis and developmental defects.
      The histone methyltransferase SET8 (also known as Pr-Set7) was previously
      reported to monomethylate Lys(20) of histone H4. However, the temporal and
      spatial control of SET8 activity remains elusive. Here, we provide evidence to
      support that SET8 monomethylates Lys(20) of histone H4 during S phase by
      tethering to proliferating cell nuclear antigen via a putative proliferating cell
      nuclear antigen-interacting protein box. In addition, we show that SET8 function
      is required for S phase progression. Finally, deletion of SET8 in mice causes
      embryonic lethality, suggesting that SET8 plays an important role in mammalian
      embryogenesis.

PMID- 18319262
TI  - Fhit interaction with ferredoxin reductase triggers generation of reactive oxygen
      species and apoptosis of cancer cells.
AB  - Fhit protein is lost in most cancers, its restoration suppresses tumorigenicity,
      and virus-mediated FHIT gene therapy induces apoptosis and suppresses tumors in
      preclinical models. We have used protein cross-linking and proteomics methods to
      characterize a Fhit protein complex involved in triggering Fhit-mediated
      apoptosis. The complex includes Hsp60 and Hsp10 that mediate Fhit stability and
      may affect import into mitochondria, where it interacts with ferredoxin
      reductase, responsible for transferring electrons from NADPH to cytochrome P450
      via ferredoxin. Viral-mediated Fhit restoration increases production of
      intracellular reactive oxygen species, followed by increased apoptosis of lung
      cancer cells under oxidative stress conditions; conversely, Fhit-negative cells
      escape apoptosis, carrying serious oxidative DNA damage that may contribute to an
      increased mutation rate. Characterization of Fhit interacting proteins has
      identified direct effectors of the Fhit-mediated apoptotic pathway that is lost
      in most cancers through loss of Fhit.

PMID- 18319263
TI  - Effect of superoxide derived from lucifer yellow CH on voltage-gated currents of
      mouse taste bud cells.
AB  - Lucifer yellow CH (LY), a fluorescent membrane-impermeable cell marker dye, has
      been routinely loaded into cells through recording electrodes to visualize these
      cells after electrophysiological investigation, without considering its
      pharmacological effect. Recently, we showed that the exposure of cells loaded
      with LY to light for microscopy produced unidentified radical species that
      retarded the inactivation of voltage-gated Na+ currents irreversibly (Higure Y et
      al. 2003). Here, we show that superoxide dismutase, an enzyme that decomposes
      superoxide, reverses the retardation effect, which assures that superoxide is the
      unidentified radical species. The estimated mean lifetime of superoxide in
      recording electrodes (in the absence of cytoplasm) is approximately 6 min, and
      hence, the Na+ currents are retarded even in the dark, when LY is exposed to
      light before being loaded into the cell. Superoxide has no effect on voltage
      gated Cl- currents. These results show that superoxide action on ion channels is
      rather selective. The breakdown of superoxide inside cells and the effect of
      endogenous superoxide on the superoxide-susceptible channels are discussed.

PMID- 18319264
TI  - Frequency analysis of the fibrillatory activity from surface ECG lead V1 and
      intracardiac recordings: implications for mapping of AF.
AB  - AIMS: Fibrillatory waves observed in the surface electrograms may be a direct
      reflection of the electrophysiologic mechanism of the atrial fibrillation (AF).
      This study compared the fibrillatory waves in the surface ECG and the individual
      intracardiac mapping sites in different types of paroxysmal AF. METHODS AND
      RESULTS: Thirty patients with paroxysmal AF originating from the pulmonary veins
      (PVs) or superior vena cava (SVC) were enrolled. Frequency analysis was performed
      on the intracardiac electrograms recorded from various mapping sites in both
      atria sequentially with simultaneous surface electrogram recordings. The SVC-AF
      patients had a trend toward a higher DF in ECG lead V1 when compared with the PV
      AF patients (7.35 +/- 2.09 vs. 5.89 +/- 0.79 Hz, P = 0.018). The mean dominant
      frequency (DF) of the LA mapping sites in the PV-AF patients was higher than that
      in the SVC-AF patients (7.06 +/- 0.66 vs. 6.13 +/- 0.96 Hz, P = 0.009), whereas
      the mean DF of the RA mapping sites was similar between the two groups (5.84 +/-
      0.80 vs. 6.26 +/- 1.11 Hz, P = NS). The intra-class correlation coefficient (ICC)
      between the mean DF of the RA sites and V1 was higher (r = 0.21, P = 0.02) when
      compared with the mean DF of the LA sites (r = -0.007, P > 0.05). Furthermore,
      the maximal ICC was observed in the anterolateral RA free wall (r = 0.84, P <
      0.001) and not the other anatomic sites of the RA and LA. CONCLUSION: The
      fibrillatory activity observed in ECG lead V1 correlated primarily with the
      activity of the anterolateral RA free wall and thus may be useful for detecting
      the AF source if it is close to that area.

PMID- 18319265
TI  - Persistent left superior vena cava: a blessing in disguise.
AB  - Persistent left superior vena cava (SVC) is an uncommon condition, usually
      encountered during cannulation of the left subclavian vein. We describe a patient
      who required a cardiac device upgrade to cardiac resynchronization implantable
      cardioverter defibrillator for biventricular failure. The presence of a
      persistent left SVC proved to be a blessing in disguise in this patient as he had
      since developed total occlusion of the left subclavian-innominate system.

PMID- 18319266
TI  - Estimation of the requirement for implantable cardioverter defibrillators for the
      primary prevention of sudden cardiac death post-myocardial infarction based on UK
      national guidelines (2006).
AB  - AIMS: To assess the impact of the new UK National Institute for Health and
      Clinical Excellence (NICE) guidelines on the incidence of implantable
      cardioverter defibrillator (ICD) indications for the primary prevention of sudden
      cardiac death following myocardial infarction (MI). METHODS AND RESULTS: We
      performed a retrospective single centre study in a District General Hospital. The
      transthoracic echocardiogram reports of all patients with a discharge diagnosis
      of MI during a 6-month period were studied. We reviewed the notes of all patients
      with an estimated left ventricular ejection fraction (LVEF) of <35% and used UK
      national guidance to assess the incidence of potential ICD indications. Five
      hundred and forty-six patients had a discharge diagnosis of MI. Fifty had
      estimated LVEF <35% and 8-11 of these met the NICE post-MI primary prevention
      criteria for ICD implantation. This gives an estimated incidence based upon our
      local population of 29-39 patients/million/year. Most of these patients (64-88%)
      were identified purely by ECG criteria (QRS > 120 ms) and LVEF. CONCLUSION: The
      latest published UK ICD data give a new implantation rate of approximately
      40/million/year. Combining our results with published data for NICE secondary
      prevention indications gives a combined ICD indication incidence of approximately
      105-115/million/year. This suggests there is currently significant under
      provision of ICD therapy in the UK.

PMID- 18319267
TI  - Successful internal defibrillation following unusual positioning of defibrillator
      lead.

PMID- 18319268
TI  - Dynamic left ventricular dyssynchrony contributes to B-type natriuretic peptide
      release during exercise in patients with systolic heart failure.
AB  - AIMS: Plasma B-type natriuretic peptide (BNP) is an emerging biomarker in heart
      failure. In this setting, the extent of left ventricular (LV) dyssynchrony
      contributes to exercise symptoms. Whether exercise-induced changes in LV
      dyssynchrony might be a trigger of BNP release has never been investigated.
      METHODS AND RESULTS: Fifty-seven patients with systolic LV dysfunction underwent
      quantitative analysis of BNP, mitral regurgitation (MR), and dyssynchrony at rest
      and during exercise. None had inducible ischaemia on perfusion imaging. By
      multiple regression analysis, end-systolic volume index (P < 0.0001), effective
      regurgitant orifice (ERO) (P < 0.001), and E/Ea (P = 0.002) emerged as
      independent determinants of BNP at baseline (R(2) = 0.67). Exercise induced a
      significant rise in BNP levels (P < 0.0001). In multivariate analysis, a smaller
      change in systolic blood pressure (P = 0.04), a larger increase in ERO (P =
      0.017), and in systolic dyssynchrony index (P = 0.006) during exercise emerged as
      independent determinants of exercise-induced increases in BNP (R(2) = 0.45).
      CONCLUSION: MR severity, volume overload, and LV filling pressure are surrogates
      of BNP at rest. During exercise, changes in BNP reflect the presence of dynamic
      changes in both LV dyssynchrony and MR severity in the absence of inducible
      ischaemia.

PMID- 18319269
TI  - The efficacy of ventricular pacing with device automaticity in paediatric
      patients.
AB  - AIMS: To compare pacemaker reprogramming and re-intervention rates in children
      with AutoCapture (AC) and conventionally (Conv) programmed devices, and to assess
      reliability of device automaticity. METHODS AND RESULTS: Data of children with AC
      (group AC, n = 49) and conventionally programmed devices (group Conv, n = 41)
      were analysed. A total of 1106 outpatient visits and 147 Holter recordings were
      screened for device reprogramming and invasive re-intervention. At 2 and 5 years,
      freedom from reprogramming differed significantly between groups (AC: 63/35% vs.
      Conv: 13/4%; P < 0.0001), whereas freedom from re-intervention was not different
      (AC: 95/90% vs. Conv: 95/85%; P = 0.26). Mean yearly rate of reprogramming was
      lower in group AC (AC: 0.67 +/- 0.55 vs. Conv: 1.13 +/- 0.82; P = 0.005). Follow
      up duration correlated with a decreasing number of reprogramming per year in
      group Conv (rho = -0.73, P < 0.001). No ventricular output reprogramming was
      required in group AC. Holter recordings required 0.07 +/- 0.13 reprogramming per
      year in group Conv, none in group AC (P < 0.001). Holter-detected lead
      dysfunction prompted re-intervention in one patient of each group. CONCLUSION:
      Estimated freedom from as well as total yearly rate of device reprogramming was
      favourable for AC-programmed devices. No difference was seen for the incidence of
      invasive re-interventions. AC ventricular output control was effective.
      Structured device follow-up and Holter recordings in specific patient groups
      remain mandatory for all devices in paediatric patients.

PMID- 18319270
TI  - Does confined placental mosaicism account for adverse perinatal outcomes in IVF
      pregnancies?
AB  - BACKGROUND: IVF singletons have poorer perinatal outcomes than singletons from
      spontaneous conceptions. This may be due to the influence of ovarian stimulation
      on the chromosomal constitution of the embryos which could be translated into
      localized chromosomal anomalies in the placenta. The aim of this study was to
      compare the incidence of confined placental mosaicism (CPM) in IVF/ICSI
      pregnancies and spontaneous conceptions. METHODS: We conducted a multi-centre
      retrospective analysis of karyotype results obtained by chorionic villus sampling
      (CVS), performed due to advanced maternal age (>or=36 years at 18 weeks of
      gestation), in the Netherlands between 1995 and 2005. RESULTS: From a total of
      322 246 pregnancies, 20 885 CVS results were analysed: 235 in the IVF/ICSI group
      and 20 650 in the control group. The mean age of women in both groups was 38.4
      years (mean difference -0.08, 95% CI -0.35 to 0.18). Data relating to the fetal
      karyotype were missing in 143 cases in the control group. When taking into
      account missing data, the incidence of CPM was lower in the IVF-ICSI group than
      in the control group, 1.3% versus 2.2% (odds ratio 0.59, 95% CI 0.19-1.85),
      whereas the incidence of fetal chromosomal anomalies was increased 4.3% versus
      2.4% (odds ratio 1.81, 95% CI 0.95-3.42). Neither differences were statistically
      significant. CONCLUSIONS: The incidence of CPM is not increased in IVF/ICSI
      pregnancies compared with spontaneous conceptions. CPM probably does not account
      for the adverse perinatal outcomes following IVF/ICSI.

PMID- 18319271
TI  - Distribution and expression of soluble epoxide hydrolase in human brain.
AB  - Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic
      acid, which function in the brain to regulate cerebral blood flow and protect
      against ischemic brain injury. EETs are converted by soluble epoxide hydrolase
      (sEH) to the corresponding inactive diol metabolites. Previous animal studies
      have indicated that sEH gene deletion or treatment with sEH inhibitors results in
      increased levels of EETs and protection against stroke-induced brain damage. To
      begin elucidating the underlying mechanism for these effects, we sought to
      determine the distribution, expression, and activity of sEH in human brain
      samples obtained from patients with no neurological changes/pathologies.
      Immunohistochemical analyses showed the distribution of sEH mainly in the
      neuronal cell bodies, oligodendrocytes, and scattered astrocytes. Surprisingly,
      in the choroid plexus, sEH was found to be highly expressed in ependymal cells.
      Vascular localization of sEH was evident in several regions, where it was highly
      expressed in the smooth muscles of the arterioles. Western blot analysis and
      enzyme assays confirmed the presence of sEH in the normal brain. Our results
      indicate differential localization of sEH in the human brain, thus suggestive of
      an essential role for this enzyme in the central nervous system. This manuscript
      contains online supplemental material at http://www.jhc.org. Please visit this
      article online to view these materials.

PMID- 18319272
TI  - Matrix mineralization as a trigger for osteocyte maturation.
AB  - The morphology of the osteocyte changes during the cell's lifetime. Shortly after
      becoming buried in the matrix, an osteocyte is plump with a rich rough
      endoplasmic reticulum and a well-developed Golgi complex. This "immature"
      osteocyte reduces its number of organelles to become a "mature" osteocyte when it
      comes to reside deeper in the bone matrix. We hypothesized that mineralization of
      the surrounding matrix is the trigger for osteocyte maturation. To verify this,
      we prevented mineralization of newly formed matrix by administration of 1
      hydroxyethylidene-1,1-bisphosphonate (HEBP) and then examined the morphological
      changes in the osteocytes in rats. In the HEBP group, matrix mineralization was
      disturbed, but matrix formation was not affected. The osteocytes found in the
      unmineralized matrix were immature. Mature osteocytes were seen in the
      corresponding mineralized matrix in the control group. The immature osteocytes in
      the unmineralized matrix failed to show immunoreactivity with anti-sclerostin
      antibody, whereas mature osteocytes in the mineralized matrix showed
      immunoreactivity in both control and HEBP groups. These findings suggest that
      mineralization of the matrix surrounding the osteocyte is the trigger for
      cytodifferentiation from a plump immature form to a mature osteocyte. The
      osteocyte appears to start secreting sclerostin only after it matures in the
      mineralized bone matrix.

PMID- 18319273
TI  - Expression and synthesis of bone morphogenetic proteins by osteoclasts: a
      possible path to anabolic bone remodeling.
AB  - Skeletal remodeling is a finely orchestrated process coupling bone formation to
      bone resorption. The dynamics of coupling is regulated by the microenvironment at
      the bone remodeling site, which in turn is influenced by the intercellular
      communication between cells like osteoclasts and osteoblasts. Understanding the
      dynamics of coupling is important in devising new therapeutic approaches to the
      treatment of skeletal diseases characterized by disturbances in the bone
      remodeling process. In this study, we report the localization of bone
      morphogenetic proteins (BMPs) in osteoclasts generated from primary cocultures of
      bone marrow cells from mouse femur and tibia with mouse calvarial osteoblasts,
      using immunocytochemistry and in situ hybridization. Positive staining was seen
      in osteoclasts for BMP-2, -4, -6, and -7. Real-time PCR was used to
      quantitatively confirm the expression of transcripts for BMP-2, BMP-4, and BMP-6
      mRNA in murine osteoclasts. Finally, the presence of BMP-2, -4, -6, and-7
      proteins was confirmed in osteoclast lysates by Western blotting. Overall, our
      data suggest a possible direct role for osteoclasts in promoting bone formation
      via expression and synthesis of BMPs, which then would play an important role in
      promoting the recruitment, proliferation, and differentiation of osteoblasts at
      bone resorption sites.

PMID- 18319274
TI  - Glomerular CD34 expression in short- and long-term diabetes.
AB  - Aging and diabetes are associated with exacerbated expression of adhesion
      molecules. Given their importance in endothelial dysfunction and their possible
      involvement in the alteration of glomerular permeability occurring in diabetes,
      we have evaluated expression of the sialomucin-type adhesion molecule CD34 in
      renal glomerular cells of normal and diabetic animals at two different ages by
      colloidal gold immunocytochemistry and immunoblotting. CD34 labeling was mostly
      assigned to the plasma membranes of glomerular endothelium and mesangial
      processes. Podocyte membranes were also labeled, but to a lesser degree. Short-
      and long-term diabetes triggers a substantial increase in immunogold labeling for
      CD34 in renal tissues compared with young normoglycemic animals. However, the
      level of labeling in old diabetic and healthy control rats is similar, suggesting
      that the effect of diabetes and aging on CD34 expression is similar but not
      synergistic. Western blotting of isolated glomerular fractions corroborated
      immunocytochemical results. Increased expression of CD34 may reflect its
      involvement in the pathogenesis of glomerular alterations related to age and
      diabetes. Alterations present in early diabetes, resembling those occurring with
      age, strengthen the concept that diabetes is an accelerated form of aging.

PMID- 18319275
TI  - Trends in overweight and obesity among 5-7-year-old White and South Asian
      children born between 1991 and 1999.
AB  - OBJECTIVE: To determine the trends in overweight and obesity among White and
      South Asian children aged 5-7 years born between 1991 and 1999 and included in
      the East Berkshire Child Health System. METHODS: Children were grouped into nine
      cohorts based on their year of birth. The UK National BMI percentile
      classification was used to classify the children as overweight and obese and to
      examine the prevalence and trends by year of birth, sex and ethnicity. RESULTS:
      Overall, more boys (10.1%; 9.7-10.6%) than girls (9.1%; 8.7-9.6%) were obese (P <
      0.003). South Asian boys were more likely to be overweight (OR 1.92; 95% CI 1.62
      2.28; P < 0.01) and obese (OR 1.53; 95% CI 1.28-1.89; P < 0.01) than South Asian
      girls. Overweight (1.77; 1.56-2.00; P < 0.05) and obesity (1.76; 1.50-2.06; P <
      0.05) were significantly higher among South Asian boys compared with their White
      counterparts (baseline). After adjusting for sex, ethnicity and year of birth,
      South Asian children were 27% more overweight (P < 0.01) and 45% more obese (P <
      0.01) compared with White children, and boys were 6% more overweight (P = 0.04)
      and 12% more obese (P = 0.003) compared with girls. There was an increasing trend
      in overweight among boys (P = 0.01) and girls (P = 0.003); and in obesity among
      boys (P < 0.001) and girls (P = 0.008) in children born from 1991 to 1999.
      CONCLUSION: There is a significant rise in childhood obesity among 5-7-year-old
      children. Overweight and obesity among South Asian boys are significantly higher
      than that among South Asian girls. This group may be at greater risk of morbidity
      and mortality related to obesity and may need to be targeted appropriately for
      interventions to reduce obesity.

PMID- 18319276
TI  - From politics to policy: a new payment approach in Medicare Advantage.
AB  - While the Medicare Advantage program's future remains contentious politically,
      the Medicare Payment Advisory Commission's (MedPAC's) recommended policy of
      financial neutrality at the local level between private plans and traditional
      Medicare ignores local market dynamics in important ways. An analysis correlating
      plan bids against traditional Medicare's local spending levels likely would
      provide an alternative method of setting benchmarks, by producing a blend of
      local and national rates. A result would be that the rural and lower-cost urban
      "floor counties" would have benchmarks below currently inflated levels but above
      what financial neutrality at the local level--MedPAC's approach--would produce.

PMID- 18319277
TI  - Development of a patient safety climate scale in Japan.
AB  - BACKGROUND: Although patient safety climate is an important factor in preventing
      adverse events in health care organizations, there is no usable Japanese scale.
      OBJECTIVE: To develop a Japanese scale to measure patient safety climate and to
      evaluate its psychometric properties. METHODS: Cross-sectional questionnaire
      survey was conducted with respect to 9 non-academic general hospitals in Japan. A
      total of 1878 health care professionals (nurses, therapists, technicians,
      pharmacists and physicians) were included in a study. RESULTS: The eight
      dimensions measuring worker attitudes (free communication flow, continuous
      improvement, reporting/rules compliance and patient/family involvement) and
      organizational factors (supervisors' safety leadership, allied professionals'
      safety leadership, patient safety committee leadership and rules/equipment
      availability) were extracted by factor analysis. The internal consistency
      (measured by Cronbach's alpha) and repeatability (measured by intraclass
      correlation) were more than 0.70 for all subscales. In addition, the mean score,
      the within-group interrater reliability statistic (r(wg)) and the correlation
      coefficients of the mean score were confirmed at the workplace level.
      CONCLUSIONS: The scale showed acceptable dimensionality, reliability and
      validity. It also provided workplace team-evaluation and a tool for assessing the
      patient safety climate at the level of the workplace.

PMID- 18319278
TI  - Non-referral of unnatural deaths to coroners and non-reporting of unnatural
      deaths on death certificates in Taiwan: implications of using mortality data to
      monitor quality and safety in healthcare.
AB  - BACKGROUND: Mortality data has often been used to monitor the quality of cardiac
      care. OBJECTIVE: To investigate the under-reporting of unnatural deaths in
      mortality data. METHOD: All patients with a main discharge diagnosis of injury
      (ICD-9-CM code 800-999) who died in 2003 or 2004 were identified through record
      linkage between hospital discharge claims data and cause of death data in Taiwan.
      Percentages of unnatural deaths that had been referred to the coroner and in
      which injury-related information was reported on the death certificate were
      estimated. RESULTS: Of 4086 known or suspected unnatural deaths, only 57%
      (2346/4086) were referred to the coroner, and in 71% (2889/4086) injury-related
      information was reported on the death certificate. The percentages of referral
      and reporting were lowest for deaths related to complications in medical and
      surgical care. In deaths related to fracture of the femur and the effects of a
      foreign body, many doctors report injury-related information on the death
      certificate but do not refer the certification of cause of death to the coroner.
      CONCLUSIONS: The sensitivity of using mortality data alone to detect known or
      suspected unnatural deaths varied according to the types of injury and external
      causes. Monitoring cause of death data linked with hospital discharge record data
      could provide a better system for discovering these unnatural deaths.

PMID- 18319279
TI  - Clinical image quality criteria for full field digital mammography: a first
      practical application.
AB  - In order to quantify the clinical quality of full-field digital mammography, a
      set of image quality parameters is developed. The set consisted of 12 image
      quality criteria and 8 physical characteristics of the image. The first set
      interrogates the visibility of anatomical structures and typical characteristics
      of a digital image, such as noise and saturation of dark and white areas. The
      second set of criteria evaluates contrast, sharpness and confidence with the
      representation of masses, microcalcifications and the image. The use of these
      criteria is reported in a retrospective study, in which the impact of dose on the
      radiological quality of digital mammograms is evaluated. Fifty patients acquired
      in a low-dose mode were retrieved and compared with 50 patients acquired in a
      dose mode that was set 41% higher. The dose affects, more than expected, contrast
      and sharpness of the image, whereas the visibility of the anatomical structures
      remains unchanged. With these parameters, quantification of the image quality is
      possible; however, because of subjectivity of the parameters, only intra-observer
      comparison and evaluation of the individual parameters rather than the overall
      results are advised. Together with physical tests of image quality, critical
      radiological evaluation of the quality should be included in the acceptance
      process of digital mammography.

PMID- 18319280
TI  - Extremity dosimetry trial: Devonport Royal Dockyard.
AB  - This trial was undertaken to assess extremity dosemeters, which were made
      available to Devonport Royal Dockyard and determine the most suitable to the
      site. The trial included operational and laboratory-based exposures. Operational
      exposures were within a submarine reactor compartment and a waste storage area.
      Laboratory exposures were undertaken using (241)Am, (137)Cs and (60)Co sources to
      compare and contrast the dosemeters energy response. In addition, the low dose
      response and the response if placed in the incorrect orientation were also
      assessed. Ten passive and two active dosemeters were tested, with three
      highlighted as the most technically suitable, DSTL Harshaw DXT-RAD, HPA Harshaw
      EXT-RAD and the AMEC Panasonic UD-807A. The most technically suitable dosemeter
      was the DSTL Harshaw DXT-RAD, due to good responses within all aspects of the
      trial and the user's preference for the ring type design. The John Caunt ED2
      electronic dosemeter 2 (ED2) also performed well, but suffered radio frequency
      interference.

PMID- 18319281
TI  - Quality assurance of computed and digital radiography systems.
AB  - Computed radiography (CR) and digital radiography (DR) are replacing traditional
      film screen radiography as hospitals move towards digital imaging and picture
      archiving and communication systems (PACS). Both IPEM and KCARE have recently
      published quality assurance and acceptance testing guidelines for DR. In this
      paper, the performance of a range of CR and DR systems is compared. Six different
      manufacturers are included. Particular attention is paid to the performance of
      the systems under automatic exposure control (AEC). The patient is simulated
      using a range of thicknesses of tissue equivalent material. Image quality
      assessment was based on detector assessment protocols and includes pixel value
      measures as well as subjective assessment using Leeds Test Objects. The protocols
      for detector assessment cover a broad range of tests and in general detectors
      (whether DR or CR) performed satisfactorily. The chief limitation in performing
      these tests was that not all systems provided ready access to pixel values.
      Subjective tests include the use of the Leeds TO20. As part of this work,
      suggested reference values are provided to calculate the TO20 image quality
      factor. One consequence of moving from film screen to digital technologies is
      that the dynamic range of digital detectors is much wider, and increased
      exposures are no longer evident from changes in image quality. As such, AEC is a
      key parameter for CR and DR. Dose was measured using a standard phantom as a
      basic means of comparing systems. In order to assess the AEC performance, exit
      doses were also measured while varying phantom thickness. Signal-to-noise ratios
      (SNRs) were calculated on a number of systems where pixel values were available.
      SNR was affected by the selection of acquisition protocol. Comparisons between
      different technologies and collation of data will help refine acceptance
      thresholds and contribute to optimising dose and image quality.

PMID- 18319282
TI  - A quantitative method for evaluating the detectability of lesions in digital
      mammography.
AB  - This study presents a quantitative method for evaluating the detectability of
      microcalcifications in digital mammography. Four hundred and twenty
      microcalcifications (with various morphology, size and contrast), simulated with
      a previously validated method, were used for the creation of image datasets.
      Lesions were inserted into 163 regions of interests of 59 selected raw digital
      mammograms with various anatomical backgrounds and acquired with a Siemens
      Novation DR. After processing, these composite images were scored by experienced
      radiologists, who located multiple simulated lesions and rated them under
      conditions of free-search. For statistical analysis, free-response receiver
      operating characteristic curves are plotted; the use of jackknife free-response
      receiver-operating characteristic method has also been investigated. The main
      advantage of this methodology is that the exact number of inserted
      microcalcifications is well known and that the lesions are fully characterised in
      terms of pathology, size, morphology and peak contrast. A first application has
      been the evaluation of the effect of anatomical background on microcalcifications
      detection. Preliminary findings in this study indicate that this method may be a
      promising tool to evaluate factors that have an influence on the detectability of
      lesions, such as the clinical processing or the viewing conditions.

PMID- 18319283
TI  - An international calibration of Kerma-Area Product meters for patient dose
      optimisation study.
AB  - The results of international calibration of Kerma Area Product (KAP) meters for
      European SENTINEL survey on patient dose optimisation of cardiac and
      interventional radiology practice are presented. Twelve countries were involved
      in the study. An investigation was conduced on 25 KAP meters fitted to undercouch
      X-ray tubes; 13 KAP meters were installed on cardiac units and the remaining 12
      on interventional ones. The simplified calibration method has been applied,
      consisting of KAP estimation by multiplying the air kerma at the centre of the X
      ray field by the irradiated area. The obtained values of calibration factors
      range from 0.4 to 0.9 and from 0.4 to 0.8 for KAP meters installed on cardiac and
      interventional units, respectively. They account also for table and mattress
      attenuation. For air kerma assessment, measurements with thermoluminescent
      dosemeters have been applied and when possible compared against an additional
      reference dosemeter. As the result of the investigation, the importance of
      calibration of KAP meters in clinical conditions that include mattress and table
      attenuation has been recognised.

PMID- 18319284
TI  - Molecular dissection of Penelope transposable element regulatory machinery.
AB  - Penelope-like elements (PLEs) represent a new class of retroelements identified
      in more than 80 species belonging to at least 10 animal phyla. Penelope isolated
      from Drosophila virilis is the only known transpositionally active representative
      of this class. Although the size and structure of the Penelope major transcript
      has been previously described in both D. virilis and D. melanogaster transgenic
      strains, the architecture of the Penelope regulatory region remains unknown. In
      order to determine the localization of presumptive Penelope promoter and enhancer
      like elements, segments of the putative Penelope regulatory region were linked to
      a CAT reporter gene and introduced into D. melanogaster by P-element-mediated
      transformation. The results obtained using ELISA to measure CAT expression levels
      and RNA studies, including RT-PCR, suggest that the active Penelope transposon
      contains an internal promoter similar to the TATA-less promoters of LINEs. The
      results also suggest that some of the Penelope regulatory sequences control the
      preferential expression in the ovaries of the adult flies by enhancing expression
      in the ovary and reducing expression in the carcass. The possible significance of
      the intron within Penelope for the function and evolution of PLEs, and the effect
      of Penelope insertions on adjacent genes, are discussed.

PMID- 18319285
TI  - Bioinformatic and functional analysis of RNA secondary structure elements among
      different genera of human and animal caliciviruses.
AB  - The mechanism and role of RNA structure elements in the replication and
      translation of Caliciviridae remains poorly understood. Several algorithmically
      independent methods were used to predict secondary structures within the
      Norovirus, Sapovirus, Vesivirus and Lagovirus genera. All showed profound
      suppression of synonymous site variability (SSSV) at genomic 5' ends and the
      start of the sub-genomic (sg) transcript, consistent with evolutionary
      constraints from underlying RNA structure. A newly developed thermodynamic
      scanning method predicted RNA folding mapping precisely to regions of SSSV and at
      the genomic 3' end. These regions contained several evolutionarily conserved RNA
      secondary structures, of variable size and positions. However, all caliciviruses
      contained 3' terminal hairpins, and stem-loops in the anti-genomic strand
      invariably six bases upstream of the sg transcript, indicating putative roles as
      sg promoters. Using the murine norovirus (MNV) reverse-genetics system,
      disruption of 5' end stem-loops produced approximately 15- to 20-fold infectivity
      reductions, while disruption of the RNA structure in the sg promoter region and
      at the 3' end entirely destroyed replication ability. Restoration of infectivity
      by repair mutations in the sg promoter region confirmed a functional role for the
      RNA secondary structure, not the sequence. This study provides comprehensive
      bioinformatic resources for future functional studies of MNV and other
      caliciviruses.

PMID- 18319286
TI  - An optimized split-ubiquitin cDNA-library screening system to identify novel
      interactors of the human Frizzled 1 receptor.
AB  - The yeast split-ubiquitin system has previously been shown to be suitable to
      detect protein interactions of membrane proteins and of transcription factors in
      vivo. Therefore, this technology complements the classical split-transcription
      factor based yeast two-hybrid system (Y2H). Success or failure of the Y2H depends
      primarily on the ability to avoid false-negative and false-positive hits that
      become a limiting factor for the value of the system, especially in large scale
      proteomic analyses. We provide here a systematic assessment of parameters to help
      improving the quality of split-ubiquitin cDNA-library screenings. We
      experimentally defined the optimal 5-fluoroorotic acid (5-FOA) concentration as a
      key parameter to increase the reproducibility of interactions and, at the same
      time, to keep non-specific background growth low. Furthermore, we show that the
      efficacy of the 5-FOA selection is modulated by the plating density of the yeast
      clones. Moreover, a reporter-specific class of false-positive hits was
      identified, and a simple phenotypic assay for efficient de-selection was
      developed. We demonstrate the application of this improved system to identify
      novel interacting proteins of the human Frizzled 1 receptor. We identified
      several novel interactors with components of the Wnt-Frizzled signalling pathways
      and discuss their potential roles as direct mediators of Frizzled receptor
      signalling. The present work is the first example of a split-ubiquitin
      interaction screen using an in-situ expressed receptor of the serpentine class,
      emphasizing the suitability of the described improvements in the screening
      protocol.

PMID- 18319287
TI  - Siring success and paternal effects in heterodichogamous Acer opalus.
AB  - BACKGROUND AND AIMS: Heterodichogamy (a dimorphic breeding system comprising
      protandrous and protogynous individuals) is a potential starting point in the
      evolution of dioecy from hermaphroditism. In the genus Acer, previous work
      suggests that dioecy evolved from heterodichogamy through an initial spread of
      unisexual males. Here, the question is asked as to whether the different morphs
      in Acer opalus, a species in which males co-exist with heterodichogamous
      hermaphrodites, differ in various components of male in fitness. METHODS: Several
      components of male fertility were analysed. Pollination rates in the male phase
      were recorded across one flowering period. Pollen viability was compared among
      morphs through hand pollinations both with pollen from a single sexual morph and
      also simulating a situation of pollen competition; in the latter experiment,
      paternity was assessed with microsatellite markers. It was also determined
      whether effects of genetic relatedness between pollen donors and recipients could
      influence the siring success. Finally, paternal effects occurring beyond the
      fertilization process were tested for by measuring the height reached by
      seedlings with different sires over three consecutive growing seasons. KEY
      RESULTS: The males and protandrous morphs had higher pollination rates than the
      protogynous morph, and the seedlings they sired grew taller. No differences in
      male fertility were found between males and protandrous individuals. Departures
      from random mating due to effects of genetic relatedness among sires and pollen
      recipients were also ruled out. CONCLUSIONS: Males and protandrous individuals
      are probably better sires than protogynous individuals, as shown by the higher
      pollination rates and the differential growth of the seedlings sired by these
      morphs. In contrast, the fertility of males was not higher than the male
      fertility of the protandrous morph. While the appearance of males in sexually
      specialized heterodichogamous populations is possible, even in the absence of a
      fitness advantage, it is not clear that males can be maintained at an
      evolutionary equilibrium with two classes of heterodichogamous hermaphrodites.

PMID- 18319288
TI  - Contribution of viral and cellular cytokines to Kaposi's sarcoma-associated
      herpesvirus pathogenesis.
AB  - Kaposi's sarcoma (KS)-associated herpesvirus is associated with the
      proliferative/malignant disorders KS, primary effusion lymphoma (PEL), and
      multicentric Castleman's disease (MCD) in patients with AIDS. In spite of recent
      advances in the treatment of KS, PEL and MCD represent therapeutic challenges.
      Recent advances in dissecting the pathogenesis of these diseases have indicated
      that the viral cytokine IL-6 and the cellular cytokines/growth factors IL-10, IL
      6, stromal cell-derived factor 1, and vascular endothelial growth factor are
      important contributors to the growth, survival, and spread of PEL and MCD and are
      therefore potential targets for drug development.

PMID- 18319289
TI  - An age-associated increase in pulmonary inflammation after burn injury is
      abrogated by CXCR2 inhibition.
AB  - Burn patients over the age of 60 are at a greater risk for developing pulmonary
      complications than younger patients. The mechanisms for this, however, have yet
      to be elucidated. The objective of this study was to determine whether increased
      chemoattraction plays a role in the age-related differences in pulmonary
      inflammation after burn injury. At 6 or 24 h after receiving sham or 15% total
      body surface area scald injury, lungs from young and aged mice were analyzed for
      leukocyte content by histological examination and immunostaining. Lungs were then
      homogenized, and levels of neutrophil chemokines, MIP-2 and KC, were measured. At
      6 h after burn, the number of neutrophils was four times higher in the lungs of
      both burn groups compared with aged-matched controls (P<0.05), but no age
      difference was evident. At 24 h, in contrast, neutrophils returned to sham levels
      in the lungs of young, burn-injured mice (P<0.05) but did not change in the lungs
      of aged, burn-injured mice. Pulmonary levels of the neutrophil chemokine KC but
      not MIP-2 were consistently three times higher in aged, burn-injured mice
      compared with young, burn-injured mice at both time-points analyzed.
      Administration with anti-CXCR2 antibody completely abrogated the excessive
      pulmonary neutrophil content by 24 h (P<0.05), while not affecting the
      inflammatory response of the wounds. These studies show that CXCR2-mediated
      chemoattraction is involved in the pulmonary inflammatory response after burn and
      suggest that aged individuals sustaining a burn injury may benefit from treatment
      strategies that target neutrophil chemokines.

PMID- 18319290
TI  - Identification and functional characterization of a bovine orthologue to DC-SIGN.
AB  - Dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN) C-type lectin is
      almost exclusively expressed at the cell surface of DC. In addition to its normal
      function facilitating contact of DC with T cells, DC-SIGN has been shown to bind
      a variety of pathogens, including Mycobacterium bovis, and HIV-1 envelope protein
      gp120. In this study, we identified the bovine ortholog of the human DC-SIGN gene
      within the bovine genome, which exists as a single copy. PCR amplified a product,
      showing a 100% match with the predicted sequences as well as a sequence predicted
      to be similar to that of SIGNR7. Furthermore, a protein with the same molecular
      weight as human DC-SIGN was detected by Western blot in cell lysate derived from
      bovine DC. To characterize this molecule functionally, the uptake of FITC-labeled
      OVA and FITC-labeled gp120 (FITC-gp120) by bovine and human DC was assessed. FITC
      gp120 was shown to bind to bovine DC in a time- and temperature-dependent manner.
      Binding was blocked by a polyclonal anti-DC-SIGN antibody but not by a control
      antibody. Furthermore, blocking of this molecule also reduced the binding of M.
      bovis bacillus Calmette-Guerin expressing GFP. Confocal microscopy showed that DC
      SIGN was expressed on the surface of bovine DC. Subsequent pulse-chase studies
      revealed that FITC-gp120 was internalized by bovine monocyte-derived DC as early
      as 10 min. Thus, there is evidence of a DC-SIGN-like molecule expressed
      specifically by bovine DC. This molecule may play an important role in the
      infection of bovine (DC) cells with M. bovis.

PMID- 18319291
TI  - Norovirus and sapovirus infections among children with acute gastroenteritis in
      Ho Chi Minh City during 2005-2006.
AB  - A molecular epidemiological study on common diarrheal viruses was conducted in a
      children's hospital in Ho Chi Minh City between December 2005 and November 2006.
      Fecal samples were collected from 502 pediatric patients with acute
      gastroenteritis, and were screened for the presence of norovirus (NoV) and
      sapovirus (SaV). NoVs GII and SaVs were detected in 6.4% and 1.2% specimens,
      respectively, while there was no NoV GI found among studied samples. NoVs could
      be identified through the year, except in April and July, with the peak of
      detection rate (62.5%) during the rainy season. Conversely, four out of six
      (66.7%) of the SaV strains were identified during the dry season. Patients aged
      between 6 and 23 months were found to be more infected by NoVs. The overall mean
      severity score of norovirus-positive patients was 9.8 +/- 3.6, and no significant
      difference of severity scores among patients belonged to different age groups,
      gender and place of living. The results of phylogenetic analysis showed the
      diversity of caliciviruses circulating in the area, and various types of
      recombination were identified among NoVs and SaVs detected. These results provide
      important information on calicivirus infections among Vietnamese children.

PMID- 18319292
TI  - Impact of an acute medical admission unit on hospital mortality: a 5-year
      prospective study.
AB  - AIM: To determine the impact of the introduction of an acute medical admission
      unit (AMAU) on all-cause hospital mortality in unselected patients undergoing
      acute medical admission to a teaching hospital. DESIGN: Analysis of data recorded
      in the hospital in-patient enquiry (HIPE) system relating to all emergency
      medical patients admitted to St James's Hospital (SJH), Dublin between 1 January
      2002 and 31 December 2006. METHODS: The reference year was 2002, during which
      patients were admitted to a variety of wards under the care of a named consultant
      physician. In 2003, two centrally located wards were re-configured to function as
      an AMAU, and all emergency medical patients were admitted to this unit following
      emergency department evaluation. Hospital mortality was obtained from a database
      of deaths occurring during this period and linked to HIPE data. RESULTS:
      Following the introduction of the AMAU process, all-cause hospital mortality
      decreased from 12.6% in 2002 to 7.0% in 2006 (P < 0.0001), representing a 44.4%
      relative reduction during the course of the 5-year observation period (P <
      0.0001). The Odds ratio (95% confidence interval) for all-cause mortality in 2006
      compared with 2002 was 0.28 (0.23, 0.35). This effect was powerfully independent
      of other covariates, including Charlson co-morbidity and illness severity score
      (APACHE II), in binary logistic regression analysis and was observed across a
      wide cross-section of diagnostic groups. CONCLUSION: The introduction of an AMAU
      significantly improved all-cause hospital mortality in acute unselected medical
      patients. The delivery of Acute Medicine may be enhanced by structural reform
      with emphasis on focus and volume. Prospective studies validating similar models
      elsewhere should be explored.

PMID- 18319293
TI  - Hypothesis: arterial glycocalyx dysfunction is the first step in the
      atherothrombotic process.
AB  - We present evidence that the 0.5 microm thick gel layer, lining the inner wall of
      healthy blood vessels, the glycocalyx, is the first line of defence against
      atherothrombotic disease. All blood vessel linings are coated with this gel, a
      highly negatively charged structure, rich in anionic sites mostly represented by
      the sialic acid moieties of glycoproteins and the sulphate and carboxyl groups of
      heparan-sulphate proteoglycans. Blood flow in arteries is associated with a shear
      stress at the glycocalyx, which signals the underlying endothelial cells to
      release nitric oxide (NO), an anti-atherogenic factor. Sites of low shear stress
      in the arterial tree are more susceptible to atheroma due to lack of NO
      generation through this mechanism, whereas exercise, by increasing blood flow and
      shear stress, is protective. We postulate that risk factors for atherothrombosis
      act by impairing glycocalyx function. That luminal hyperglycaemia causes
      glycocalyx dysfunction has already been shown; we postulate this to be the first
      step in the atherothrombotic process in patients with diabetes mellitus and
      metabolic syndrome (insulin resistance). There is also evidence of glycocalyx
      defects from exposure to oxidized low-density lipoprotein. We postulate that
      other risk factors will have a similar action on the glycocalyx as the initiating
      factor in the disease process, e.g. smoking, hyperlipidaemias and
      hyperhomocystenaemia. These predictions can now be tested in a large animal model
      of shear-stress-mediated arterial dilatation.

PMID- 18319294
TI  - An unusual haversack on the shoulder.

PMID- 18319295
TI  - Predicting outcome in acute organophosphorus poisoning with a poison severity
      score or the Glasgow coma scale.
AB  - BACKGROUND: Organophosphorus (OP) pesticide poisoning kills around 200,000 people
      each year, principally due to self-poisoning in the Asia-Pacific region. AIM: We
      wished to assess whether patients at high risk of death could be identified
      accurately using clinical parameters soon after hospital admission. DESIGN: We
      evaluated the usefulness of the International Program on Chemical Safety Poison
      Severity Score (IPCS PSS) and the Glasgow Coma Score (GCS) prospectively for
      predicting death in patients poisoned by OP pesticides. METHODS: Data were
      collected as part of a multicenter cohort study in Sri Lanka. Study doctors saw
      all patients on admission, collecting data on pulse, blood pressure, pupil size,
      need for intubation and GCS. RESULTS: Of the patients, 1365 with a history of
      acute OP poisoning were included. Receiver operating characteristic (ROC) curves
      were calculated for the IPCS PSS and GCS on admission. The IPCS PSS and GCS had
      similar ROC area under the curves (AUC) and best cut points as determined by
      Youden's index (AUC/sensitivity/specificity 0.81/0.78/0.79 for IPCS PSS > or =
      grade 2 and 0.84/0.79/0.79 for GCS < or = 13). The predictive value varied with
      the pesticide ingested, being more accurate for dimethoate poisoning and less
      accurate for fenthion poisoning (GCS AUC 0.91 compared with 0.69). CONCLUSION:
      GCS and the IPCS PSS were similarly effective at predicting outcome. Patients
      presenting with a GCS < or = 13 need intensive monitoring and treatment. However,
      the identity of the organophosphate must be taken into account, since the half of
      all patients who died from fenthion poisoning only had mild symptoms at
      presentation.

PMID- 18319296
TI  - A systematic review of vanadium oral supplements for glycaemic control in type 2
      diabetes mellitus.
AB  - OBJECTIVE: To assess the effectiveness of oral vanadium supplementation for
      glycaemic control in type 2 diabetes by conducting a systematic review of the
      literature. DESIGN AND METHODS: Eligible studies were identified by searching 14
      databases using standardized terms. Experts, study authors and manufacturers were
      also contacted. Hand-searching was not undertaken. Selection criteria for
      inclusion in the review were controlled human trials of vanadium vs. placebo in
      adults with type 2 diabetes of minimum 2 months duration, and a minimum of 10
      subjects per arm. Data extraction, assessment of study quality and outcome
      analysis were undertaken by two independent reviewers. RESULTS: One hundred and
      fifty one studies were found but none met the inclusion criteria. We proceeded to
      summarize the state of existing evidence and plan for a future clinical trial by
      applying revised, less restrictive criteria to our search, for clinical trials of
      30-150 mg daily oral vanadium supplementation in diabetic humans. Only five were
      identified. These demonstrated significant treatment-effects, but due to poor
      study quality, must be interpreted with caution. Treatment with vanadium often
      results in gastrointestinal side-effects. CONCLUSION: There is no rigorous
      evidence that oral vanadium supplementation improves glycaemic control in type 2
      diabetes. The routine use of vanadium for this purpose cannot be recommended. A
      large-scale randomized controlled trial is needed to address this clinical
      question.

PMID- 18319297
TI  - Efficacy of antidepressants.

PMID- 18319298
TI  - The non-cancer mortality experience of male workers at British Nuclear Fuels plc,
      1946-2005.
AB  - BACKGROUND: Recent studies of the Hiroshima and Nagasaki A-bomb survivors,
      together with some (but not all) cohorts exposed occupationally or medically to
      ionizing radiation, have found an increasing trend in mortality from non
      malignant disease with increasing radiation dose. The aim of this study was to
      establish whether such a trend could be found in a large cohort of employees in
      the UK nuclear industry. METHODS: The cohort comprised 64 937 individuals ever
      employed at the study sites between 1946 and 2002, followed up to 2005; radiation
      exposures as measured by personal dosimeters ('film badges') were available for
      42 426 individuals classified as 'radiation workers'. Poisson regression models
      were used to investigate the relationship between excess mortality rates and
      cumulative radiation exposure, using both relative and additive risk models.
      RESULTS: The cohort shows a pronounced 'healthy worker' effect. Overall, socio
      economic status as indicated by employment status has a greater influence on
      mortality than does radiation exposure status. For male radiation workers, there
      is an apparent dose response for mortality from circulatory system disease [P <
      0.001, ERR = 0.65 (90% CI 0.36-0.98) Sv(-1)]. However there is evidence for
      inhomogeneity in the apparent dose response (P = 0.016), arising principally at
      cumulative doses in excess of 300 mSv, when the four categories of employment and
      radiation exposure status are examined separately. CONCLUSIONS: We have found
      evidence for an association between mortality from non-cancer causes of death,
      particularly circulatory system disease, and external exposure to ionizing
      radiation in this cohort. However, the tentative nature of biological mechanisms
      that might explain such an effect at low chronic doses and the above
      inhomogeneities in apparent dose-response, mean that the results of our analysis
      are not consistent with any simple causal interpretation. Further work is
      required to explain these inhomogeneities, and on the possible role of factors
      associated with socio-economic status and shift working, before any further
      conclusions can be drawn.

PMID- 18319299
TI  - Microneme protein 8--a new essential invasion factor in Toxoplasma gondii.
AB  - Apicomplexan parasites rely on sequential secretion of specialised secretory
      organelles for the invasion of the host cell. First, micronemes release their
      content upon contact with the host cell. Second, rhoptries are discharged,
      leading to the formation of a tight interaction (moving junction) with the host
      cell, through which the parasite invades. The functional characterisation of
      several micronemal proteins in Toxoplasma gondii suggests the occurrence of a
      stepwise process. Here, we show that the micronemal protein MIC8 of T. gondii is
      essential for the parasite to invade the host cell. When MIC8 is not present, a
      block in invasion is caused by the incapability of the parasite to form a moving
      junction with the host cell. We furthermore demonstrate that the cytosolic domain
      is crucial for the function of MIC8 and can not be functionally complemented by
      any other micronemal protein characterised so far, suggesting that MIC8
      represents a novel, functionally distinct invasion factor in this apicomplexan
      parasite.

PMID- 18319300
TI  - Structural basis for the nuclear import of the human androgen receptor.
AB  - Ligand-dependent nuclear import is crucial for the function of the androgen
      receptor (AR) in both health and disease. The unliganded AR is retained in the
      cytoplasm but, on binding 5alpha-dihydrotestosterone, it translocates into the
      nucleus and alters transcription of its target genes. Nuclear import of AR is
      mediated by the nuclear import factor importin-alpha, which functions as a
      receptor that recognises and binds to specific nuclear localisation signal (NLS)
      motifs on cargo proteins. We show here that the AR binds to importin-alpha
      directly, albeit more weakly than the NLS of SV40 or nucleoplasmin. We describe
      the 2.6-angstroms-resolution crystal structure of the importin-alpha-AR-NLS
      complex, and show that the AR binds to the major NLS-binding site on importin
      alpha in a manner different from most other NLSs. Finally, we have shown that
      pathological mutations within the NLS of AR that are associated with prostate
      cancer and androgen-insensitivity syndrome reduce the binding affinity to
      importin-alpha and, subsequently, retard nuclear import; surprisingly, however,
      the transcriptional activity of these mutants varies widely. Thus, in addition to
      its function in the nuclear import of AR, the NLS in the hinge region of AR has a
      separate, quite distinct role on transactivation, which becomes apparent once
      nuclear import has been achieved.

PMID- 18319301
TI  - Cdc42- and Rac1-mediated endothelial lumen formation requires Pak2, Pak4 and
      Par3, and PKC-dependent signaling.
AB  - Rho GTPases regulate a diverse spectrum of cellular functions involved in
      vascular morphogenesis. Here, we show that Cdc42 and Rac1 play a key role in
      endothelial cell (EC) lumen and tube formation as well as in EC invasion in three
      dimensional (3D) collagen matrices and that their regulation is mediated by
      various downstream effectors, including Pak2, Pak4, Par3 and Par6. RNAi-mediated
      or dominant-negative suppression of Pak2 or Pak4, two major regulators of
      cytoskeletal signaling downstream of Cdc42 or Rac1, markedly inhibits EC lumen
      and tube formation. Both Pak2 and Pak4 phosphorylation strongly correlate with
      the lumen formation process in a manner that depends on protein kinase C (PKC)
      mediated signaling. We identify PKCepsilon and PKCzeta as regulators of EC
      lumenogenesis in 3D collagen matrices. Two polarity proteins, Par3 and Par6, are
      also required for EC lumen and tube formation, as they establish EC polarity
      through their association with Cdc42 and atypical PKC. In our model, disruption
      of any member in the Cdc42-Par3-Par6-PKCzeta polarity complex impairs EC lumen
      and tube formation in 3D collagen matrices. This work reveals novel regulators
      that control the signaling events mediating the crucial lumen formation step in
      vascular morphogenesis.

PMID- 18319302
TI  - Phenotype reversion in fetal human liver epithelial cells identifies the role of
      an intermediate meso-endodermal stage before hepatic maturation.
AB  - Understanding the biological potential of fetal stem/progenitor cells will help
      define mechanisms in liver development and homeostasis. We isolated epithelial
      fetal human liver cells and established phenotype-specific changes in gene
      expression during continuous culture conditions. Fetal human liver epithelial
      cells displayed stem cell properties with multilineage gene expression, extensive
      proliferation and generation of mesenchymal lineage cells, although the initial
      epithelial phenotype was rapidly supplanted by meso-endodermal phenotype in
      culture. This meso-endodermal phenotype was genetically regulated through
      cytokine signaling, including transforming growth factor beta, bone morphogenetic
      protein, fibroblast growth factor and other signaling pathways. Reactivation of
      HNF3alpha (FOXA1) transcription factor, a driver of hepatic specification in the
      primitive endoderm, indicated that the meso-endodermal phenotype represented an
      earlier developmental stage of cells. We found that fetal liver epithelial cells
      formed mature hepatocytes in vivo, including after genetic manipulation using
      lentiviral vectors, offering convenient assays for analysis of further cell
      differentiation and fate. Taken together, these studies demonstrate plasticity in
      fetal liver epithelial stem cells, offer paradigms for defining mechanisms
      regulating lineage switching in stem cells, and provide potential avenues for
      regulating cell phenotypes for applications of stem cells, such as for cell
      therapy.

PMID- 18319303
TI  - PAK is required for the disruption of E-cadherin adhesion by the small GTPase
      Rac.
AB  - E-cadherin cell-cell adhesion plays a major role in the maintenance of the
      morphology and function of epithelial tissues. Modulation of E-cadherin function
      is an important process in morphogenesis and tumour de-differentiation. We have
      previously shown that constitutively active Rac1 induces the disassembly of E
      cadherin complexes from junctions in human keratinocytes. Here, we compare this
      activity in three members of the Rac subfamily (Rac1, Rac3 and Rac1b) and
      investigate the molecular mechanisms underlying Rac1-induced destabilization of
      junctions. We demonstrate that Rac3 shares with Rac1 the ability to interfere
      with cadherin-mediated adhesion. Rac1b is an alternative splice variant of Rac1
      but, surprisingly, Rac1b cannot induce junction disassembly. Thus, Rac family
      members differ on their potential to perturb keratinocyte cell-cell contacts. The
      mechanism through which Rac promotes disassembly of cadherin-dependent adhesion
      does not involve an increase in contractility. Instead, activation of the Rac
      target PAK1 is necessary for destabilization of cell-cell contacts. Inhibition of
      PAK1 by dominant-negative constructs or depletion of endogenous PAK1 by RNA
      interference efficiently blocked Rac1-induced perturbation of junctions.
      Interestingly, PAK1 cannot be activated by Rac1b, suggesting that this may
      contribute to the inability of Rac1b to disrupt cell-cell contacts in
      keratinocytes. As PAK1 also plays a crucial role in lamellipodia formation, our
      data indicate that PAK1 is at the interface between junction destabilization and
      increased motility during morphogenetic events.

PMID- 18319304
TI  - Elevated epidermal growth factor receptor phosphorylation induces resistance
      artery dysfunction in diabetic db/db mice.
AB  - OBJECTIVE: We previously showed epidermal growth factor receptor (EGFR)
      transactivation to be key mechanism in the regulation of resistance artery
      myogenic tone. Type 2 diabetes is associated with microvascular complications. We
      hypothesized that elevated EGFR phosphorylation contributes to resistance artery
      dysfunction in type 2 diabetes. RESEARCH DESIGN AND METHODS AND RESULTS: Diabetic
      db/db and nondiabetic (control) mice were treated with EGFR inhibitor (AG1478; 10
      mg x kg(-1) x day(-1)) for 2 weeks. Isolated coronary artery and mesenteric
      resistance artery (MRA) were mounted in an arteriograph. Pressure-induced
      myogenic tone was increased in MRA and coronary artery from diabetic mice and
      normalized by AG1478. Phenylephrine-induced contraction and nitric oxide donor
      induced relaxation were similar in all groups. Endothelium-dependent relaxation
      in response to shear stress and acetylcholine of MRA and coronary artery from
      diabetic mice was altered and associated with reduced endothelial nitric oxide
      synthase (eNOS) expression and phosphorylation. Treated diabetic mice with AG1478
      improved coronary artery and MRA endothelial function and restored eNOS
      expression. Immunostaining and Western blot analysis showed increased endothelial
      and smooth muscle cell EGFR phosphorylation of MRA and coronary artery from
      diabetic mouse, which was reduced by AG1478. Primary cultured endothelial cells
      from resistance arteries treated with high glucose for 48 h showed an increase of
      EGFR phosphorylation associated with eNOS expression and phosphorylation decrease
      in response to calcium ionophore. Pretreatment of endothelial cells with AG1478
      prevented the effect of high glucose. CONCLUSIONS: This study provides evidence
      of the role of elevated EGFR phosphorylation in coronary artery and MRA
      dysfunction in diabetic db/db mice. Therefore, EGFR should be a potential target
      for overcoming diabetic small artery complications.

PMID- 18319305
TI  - Thyroid diseases in atomic bomb survivors exposed in utero.
AB  - OBJECTIVE: The objective of the study was to evaluate the association of thyroid
      disease with radiation dose in atomic bomb survivors exposed in utero. DESIGN:
      This was a cross-sectional study. SETTING: The study was conducted in atomic bomb
      survivors in Hiroshima and Nagasaki, Japan. PARTICIPANTS: Participants included
      328 atomic bomb survivors exposed in utero (mean age 55.2 yr, 162 males) who
      participated in the thyroid study at the Radiation Effects Research Foundation.
      Examinations were conducted between March 2000 and February 2003. MAIN OUTCOME
      MEASURES: The relationships of various thyroid conditions to atomic bomb
      radiation dose were measured. RESULTS: Among the 319 participants excluding nine
      participants whose exposure radiation dose was not estimated, the mean maternal
      uterine radiation dose was 0.256 Gy. We observed no significant dose-response
      relationship for the prevalence of solid thyroid nodules (odds ratio at 1 Gy,
      2.78; 95% confidence interval 0.50-11.80, P = 0.22), but the risk estimate was
      similar to the estimate for childhood exposures. The prevalence of cysts and
      autoimmune thyroid diseases was not associated with radiation dose (P > 0.30). We
      could not evaluate the dose response for malignant tumors or benign nodules due
      to the small number of cases. CONCLUSIONS: We did not observe a statistically
      significant linear dose response to radiation for thyroid nodules or autoimmune
      thyroid diseases 55-58 yr after participants' in utero exposure. However, the
      risk estimate for solid thyroid nodules was similar for those exposed in utero
      and those exposed in childhood. Because the study had limited statistical power
      to detect moderately sized effects, further studies are needed for a definitive
      conclusion.

PMID- 18319306
TI  - Metformin treatment for four years to reduce total and visceral fat in low birth
      weight girls with precocious pubarche.
AB  - CONTEXT AND OBJECTIVE: A low birth weight (LBW) tends to be followed by
      overweight due to an excess of fat, including visceral fat. LBW girls with
      precocious pubarche (PP) (pubic hair < 8 yr) are at high risk for developing an
      adipose state of hyperinsulinemic androgen excess that leads toward early
      menarche. We explored the effects of insulin sensitization with metformin in LBW
      PP girls. SETTING, DESIGN, PATIENTS, INTERVENTION: Prepubertal LBW girls with PP
      (mean body weight 2.4 kg; age 7.9 yr; body mass index 18.4 kg/m(2)) were studied.
      Girls were randomly assigned to remain untreated (n=19) or receive metformin for
      4 yr (n = 19; 425 mg/d for 2 yr, then 850 mg/d for 2 yr). MAIN OUTCOMES: At the
      start and after 4 yr, height, weight, fasting insulin, glucose, IGF-I,
      testosterone, lipids, leptin, high molecular weight adiponectin, body composition
      by absorptiometry, abdominal fat partitioning (only 4 yr) by magnetic resonance
      imaging, and menarcheal status were determined. RESULTS: Metformin-treated girls
      gained on average 5.5 kg (or approximately 50%) less fat, after 4 yr were less
      insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less
      atherogenic lipid profile, and were less likely to be post-menarcheal than
      untreated girls, whereas their gain in height, lean mass, and bone mineral
      density were similar. After 4 yr, untreated girls had more visceral fat, a higher
      ratio of visceral-to-sc fat, and a higher leptin-to-high molecular weight
      adiponectin ratio (all approximately 50% higher) than metformin-treated girls.
      CONCLUSION: Long-term metformin treatment appears to reduce total and visceral
      fat in LBW-PP girls, and to delay menarche without attenuating linear growth,
      thereby opening the perspective that adult height may be increased.

PMID- 18319307
TI  - p.H62L, a rare mutation of the CYP21 gene identified in two forms of 21
      hydroxylase deficiency.
AB  - CONTEXT: Steroid 21-hydroxylase deficiency is the most common enzymatic defect
      causing congenital adrenal hyperplasia with good genotype/phenotype relationships
      for common mutations. To determine the severity of rare mutations is essential
      for genetic counseling and better understanding of the structure-function of the
      cytochrome P450c21. OBJECTIVE: The p.H62L mutation was the most frequent of 60
      new mutations detected in 2900 steroid 21-hydroxylase deficiency patients, either
      isolated or associated on the same allele with a mild mutation (p.P453S, p.P30L,
      or partial promoter). Because phenotypes seemed to differ between patients with
      isolated or associated p.H62L, a detailed phenotype description and functional
      studies were performed. RESULTS: Regarding phenotype, patients with isolated
      p.H62L had a nonclassical form, whereas patients with the association p.H62L +
      mild mutation had a simple virilizing form. Functional studies showed that p.H62L
      reduced the conversion of the two substrates, progesterone and 17
      hydroxyprogesterone, in the same way as the mild p.P453S; the association p.H62L
      + p.P453S decreased enzymatic activity more strongly while conserving residual
      activity at a level intermediate between p.P453S and p.I172N. This suggested that
      p.H62L was a mild mutation, whereas a synergistic effect occurred when it was
      associated. Analysis of p.H62L in a three-dimensional model structure of the
      CYP21 protein explained the observed in vitro effects, the H62 being located in a
      domain implied in membrane anchoring. CONCLUSION: According to phenotype and
      functional studies, p.H62L is a mild mutation, responsible for a more severe
      phenotype when associated with another mild mutation. These data are important
      for patient management and genetic counseling.

PMID- 18319308
TI  - 24-hour serum levels of growth hormone, prolactin, and cortisol in pre- and
      postmenopausal women: the effect of combined estrogen and progestin treatment.
AB  - OBJECTIVE: Our objective was to study the 24-h profiles of GH, prolactin (PRL),
      and cortisol concentrations in older postmenopausal and middle-aged premenopausal
      women, before and after estrogen-progestin treatment (EPT). DESIGN: The study was
      a randomized, placebo-controlled, double-blind trial. GH, PRL, and cortisol were
      sampled every 20 min for 24 h in 18 postmenopausal (aged 58-70 yr) and 17
      premenopausal (aged 45-51 yr) women before and after 6 months of EPT. RESULTS:
      The mean 24-h GH (1.0 vs. 1.8 mU/liter, P = 0.033) and PRL (6.8 vs. 10.0 ng/ml, P
      = 0.009) concentrations were lower in postmenopausal than in premenopausal women.
      After EPT, the postmenopausal GH and PRL did not differ from premenopausal
      baseline levels. Postmenopausal mean 24-h GH (P < 0.001) and PRL (P = 0.002),
      daytime GH (P < 0.001) and nighttime PRL (P = 0.004) were higher during EPT
      compared with placebo. Cortisol levels did not differ. Premenopausal mean
      nighttime PRL (P = 0.026) and cortisol (P = 0.018) were higher during EPT
      compared with placebo. Postmenopausal PRL and premenopausal GH and PRL
      concentrations were higher at night than during the day. EPT did not alter this
      pattern. CONCLUSIONS: Menopause was associated with decreased 24-h levels of GH
      and PRL, which were reversible with EPT. In contrast, cortisol levels were not
      affected by menopause or EPT. In middle-aged premenopausal women, the studied
      effects of EPT were limited to nighttime increases of PRL and cortisol.

PMID- 18319309
TI  - Effects in postmenopausal women of estradiol and medroxyprogesterone alone and
      combined on resistance artery function and endothelial morphology and movement.
AB  - CONTEXT: Endothelial dysfunction in resistance arteries after menopause is
      important for the development of high blood pressure and cardiovascular disease.
      OBJECTIVES: Our objectives were to study the effects of different hormone
      replacement therapies on the function and morphology of isolated resistance
      arteries, and to look for their mechanistic basis. DESIGN AND SETTING: This was a
      randomized, placebo-controlled double-blind study in a University hospital, along
      with laboratory based studies. PATIENTS AND INTERVENTIONS: We isolated resistance
      arteries in sc biopsies from 55 postmenopausal women before and after 3-month
      therapy with estradiol (E2), medroxyprogesterone acetate (MPA), E2 plus MPA, or
      placebo. In addition, we studied isolated human endothelial cells. MAIN OUTCOME
      MEASURES AND RESULTS: Artery flow-mediated dilatation was augmented after
      treatment with E2 or E2 plus MPA, whereas MPA or placebo had no effect. Pressure
      induced myogenic tone was reduced by E2 plus MPA, whereas it was unchanged in the
      other groups. Scanning microscopy showed that E2 improved endothelial cell
      morphology and decreased signs of endothelial apoptosis, but the addition of MPA
      impaired these events. E2, MPA, or the combination all increased the expression
      and phosphorylation of the actin-binding protein, moesin and of the focal
      adhesion complex controller, focal adhesion kinase, and induced the rearrangement
      of cytoskeletal actin and vinculin fibers. All treatments promoted endothelial
      cell horizontal migration, with E2 inducing the strongest effect. CONCLUSIONS:
      This study suggests that hormone replacement therapy with estrogens or in
      combination with MPA may benefit the function of resistance arteries and may
      preserve the morphological integrity of endothelial cells by regulatory actions
      on the cytoskeleton.

PMID- 18319310
TI  - Connective tissue growth factor and susceptibility to renal and vascular disease
      risk in type 1 diabetes.
AB  - OBJECTIVE: We explored the relevance and significance of connective tissue growth
      factor (CTGF) as a determinant of renal and vascular complications among type 1
      diabetic patients. METHODS AND RESULTS: We measured the circulating and urinary
      levels of CTGF and CTGF N fragment in 1050 subjects with type 1 diabetes from the
      Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions
      and Complications (DCCT/EDIC) Study cohort. We found that hypertensive diabetic
      subjects have significantly higher levels of plasma log CTGF N fragment relative
      to normotensive subjects (P = 0.0005). Multiple regression analysis showed a
      positive and independent association between CTGF N fragment levels and log
      albumin excretion rate (P < 0.0001). In categorical analysis, patients with
      macroalbuminuria had higher levels of CTGF N fragment than diabetic subjects with
      or without microalbuminuria (P < 0.0001). Univariate and multiple regression
      analyses demonstrated an independent and significant association of log CTGF N
      fragment with the common and internal carotid intima-media thickness. The
      relative risk for increased carotid intima-media thickness was higher in patients
      with concomitantly elevated plasma CTGF N fragment and macroalbuminuria relative
      to patients with normal plasma CTGF N fragment and normal albuminuria (relative
      risk = 4.76; 95% confidence interval, 2.21-10.25; P < 0.0001). CONCLUSION: These
      findings demonstrate that plasma CTGF is a risk marker of diabetic renal and
      vascular disease.

PMID- 18319311
TI  - Osteoprotegerin Lys3Asn polymorphism and the risk of fracture in older women.
AB  - CONTEXT: Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator
      nuclear factor kappa-beta that blocks osteoclastic bone resorption. OBJECTIVE: We
      investigated the association between a Lys3Asn polymorphism in the OPG gene and
      bone mineral density (BMD), and the risk of fracture in 6695 women aged 65 yr and
      older participating in the Study of Osteoporotic Fractures. DESIGN: BMD was
      measured using either single-photon absorptiometry (Osteon Osteoanalyzer; Dove
      Medical Group, Los Angeles, CA) or dual-energy x-ray absorptiometry (Hologic QDR
      1000; Hologic, Inc., Bedford, MA). Incident fractures were confirmed by physician
      adjudication of radiology reports. Genotyping was performed using an immobilized
      probe-based assay. RESULTS: Women who were homozygous for the minor G (Lys)
      allele had significantly lower BMD at the intertrochanter, distal radius, lumbar
      spine, and calcaneus than those with the C (Asn) allele. There were 701 incident
      hip fractures during 13.6-yr follow-up (91,249 person-years), including 362
      femoral neck and 333 intertrochanteric hip fractures. Women with the C/C (Asn
      Asn) genotype had a 51% higher risk of femoral neck fracture (95% confidence
      interval, 1.13-2.02) and 26% higher risk of hip fracture (95% confidence
      interval, 1.02-1.54) than those with the G/G (Lys-Lys) genotype. These
      associations were independent of BMD. Intertrochanteric fractures were not
      associated with the Lys3Asn polymorphism. CONCLUSION: These results require
      confirmation but suggest a role for the OPG Lys3Asn polymorphism in the genetic
      susceptibility to hip fractures among older white women.

PMID- 18319312
TI  - Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms,
      and implications of a rare genetic disorder.
AB  - CONTEXT: Primary generalized glucocorticoid resistance is a rare genetic
      condition characterized by generalized, partial, target-tissue insensitivity to
      glucocorticoids. We review the clinical aspects, molecular mechanisms, and
      implications of this disorder. EVIDENCE ACQUISITION: We conducted a systematic
      review of the published, peer-reviewed medical literature using MEDLINE (1975
      through February 2008) to identify original articles and reviews on this topic.
      EVIDENCE SYNTHESIS: We have relied on the experience of a number of experts in
      the field, including our extensive personal experience. CONCLUSIONS: The clinical
      spectrum of primary generalized glucocorticoid resistance is broad, ranging from
      asymptomatic to severe cases of hyperandrogenism, fatigue, and/or
      mineralocorticoid excess. The molecular basis of the condition has been ascribed
      to mutations in the human glucocorticoid receptor (hGR) gene, which impair
      glucocorticoid signal transduction and reduce tissue sensitivity to
      glucocorticoids. A consequent increase in the activity of the hypothalamic
      pituitary-adrenal axis compensates for the reduced sensitivity of peripheral
      tissues to glucocorticoids at the expense of ACTH hypersecretion-related
      pathology. The study of functional defects of natural hGR mutants enhances our
      understanding of the molecular mechanisms of hGR action and highlights the
      importance of integrated cellular and molecular signaling mechanisms for
      maintaining homeostasis and preserving normal physiology.

PMID- 18319313
TI  - Regulation of ovarian cancer cell viability and sensitivity to cisplatin by
      progesterone receptor membrane component-1.
AB  - CONTEXT: Progesterone (P4) influences ovarian cancer cells by an unknown
      mechanism. OBJECTIVE: The objective was to determine whether P4 acts through
      progesterone receptor membrane component-1 (PGRMC1) in ovarian cancers. DESIGN,
      SETTING AND PATIENTS: Archival tissue and cDNA provided by OriGene were used for
      expression studies. In vitro experiments were conducted with Ovcar-3 cells. MAIN
      OUTCOME MEASURES: PCR, Western blot, and immunohistochemistry were used to
      measure expression of PGRMC1 and nuclear progesterone receptor (PGR). PGRMC1's
      role in regulating the viability of ovarian cancers was assessed by
      overexpressing PGRMC1, depleting PGRMC1 using small interfering RNA, and
      attenuating PGRMC1's action with a blocking antibody. Apoptosis was determined by
      4',6'-diamino-2-phenylindole staining. RESULTS: PGRMC1 mRNA increased and PGR
      mRNA decreased in advanced stages of ovarian cancer. Unlike PGR, PGRMC1 was
      expressed in virtually every cancer cell within the tumor. A similar relationship
      between PGRMC1 and PGR was observed in Ovcar-3 cells. In these cells P4
      suppressed apoptosis induced by either serum withdrawal or cisplatin (CDDP).
      Moreover, in the presence of P4, the following occurs: 1) overexpression of
      PGRMC1 reduces the effectiveness of CDDP, 2) depletion of PGRMC1 with small
      interfering RNA enhances the effects of CDDP, and 3) PGRMC1 antibody treatment
      increases the apoptotic response to CDDP. CONCLUSIONS: These findings indicate
      that PGRMC1 plays an important role in promoting ovarian cancer cell viability
      and that attenuating PGRMC1's action makes the ovarian cancer cells more
      sensitive to CDDP. These data suggest that targeted depletion of PGRMC1 could be
      useful as an adjunct to CDDP therapy.

PMID- 18319314
TI  - Low testosterone levels are common and associated with insulin resistance in men
      with diabetes.
AB  - CONTEXT: Low testosterone levels are common in men with type 2 diabetes and may
      be associated with insulin resistance. OBJECTIVE: We investigated prevalence of
      testosterone deficiency and the relationship between testosterone and insulin
      resistance in a large cohort of men with type 2 and type 1 diabetes. DESIGN: The
      study was a cross-sectional survey of 580 men with type 2 diabetes and 69 men
      with type 1 diabetes. A subgroup of 262 men with type 2 diabetes was then
      reassessed after a median of 6 months. RESULTS: Forty-three percent of men with
      type 2 diabetes had a reduced total testosterone, and 57% had a reduced
      calculated free testosterone. Only 7% of men with type 1 diabetes had low total
      testosterone. By contrast, 20.3% of men with type 1 diabetes had low calculated
      free testosterone, similar to that observed in type 2 diabetes (age-body mass
      index adjusted odds ratio = 1.4; 95% confidence interval = 0.7-2.9). Low
      testosterone levels were independently associated with insulin resistance in men
      with type 1 diabetes as well as type 2 diabetes. Serial measurements also
      revealed an inverse relationship between changes in testosterone levels and
      insulin resistance. CONCLUSIONS: Testosterone deficiency is common in men with
      diabetes, regardless of the type. Testosterone levels are partly influenced by
      insulin resistance, which may represent an important avenue for intervention,
      whereas the utility of testosterone replacement remains to be established in
      prospective trials.

PMID- 18319315
TI  - Does osteoprotegerin or receptor activator of nuclear factor-kappaB ligand
      mediate the association between bone and coronary artery calcification?
AB  - CONTEXT: Accumulating evidence indicates that vascular and bone mineralization
      may be related, although the exact mechanism remains unknown. OBJECTIVE: Our
      objective was to investigate whether an observed inverse association between bone
      mineral density (BMD) and coronary artery calcification (CAC) in postmenopausal
      women currently taking estrogen therapy is mediated by osteoprotegerin (OPG) or
      receptor activator of nuclear factor-kappaB ligand (RANKL). DESIGN: Participants
      were 92 postmenopausal women (aged 58-81 yr) taking estrogen therapy who had hip
      and spine BMD assessed by dual-energy x-ray absorptiometry and CAC measured by
      electron-beam computed tomography in 1998-2002 and serum RANKL and OPG levels
      measured in samples collected in 1997-1999. Total CAC score was dichotomized as
      none/minimal (</=10) vs. some (>10). RESULTS: OPG serum levels were higher in
      women who had some CAC compared with those who had none/minimal (126.8 +/- 1.08
      vs. 102.9 +/- 1.07 pg/ml, respectively, P = 0.03); these differences became
      nonsignificant after adjustment for age and other risk factors (P = 0.51). A 1 sd
      increase in hip BMD was associated with significantly lower odds of having CAC >
      10 (odds ratio = 0.52; 95% confidence interval = 0.29-0.93) independent of age,
      fat-free mass, high-density lipoprotein cholesterol, current smoking, and use of
      cholesterol-lowering medications. Other skeletal sites demonstrated a similar
      pattern. Addition of RANKL and/or OPG to the model had minimal effect on the
      magnitude or statistical significance of the BMD-CAC association. Additionally, a
      test of interaction indicated that RANKL and OPG are not significant effect
      modifiers. CONCLUSIONS: Serum OPG and RANKL do not account for the observed
      association between bone and coronary artery calcification among postmenopausal
      women using hormone therapy.

PMID- 18319316
TI  - 1H magnetic resonance spectroscopy in monocarboxylate transporter 8 gene
      deficiency.
AB  - CONTEXT: In monocarboxylate transporter 8 (MCT8) gene deficiency, a syndrome
      combining thyroid and neurological abnormalities, the central nervous system has
      not yet been characterized by magnetic resonance (MR) spectroscopy. OBJECTIVE: We
      studied whether the degree of dysmyelinization in MCT8 gene deficiency according
      to MR imaging (MRI) is coupled with abnormalities in brain metabolism. DESIGN:
      MRI and MR spectroscopy of the brain were performed twice in two MCT8 gene
      deficiency patients, for the first time at age 8-10 months and for the second
      time at age 17-28 months. The results were compared with those obtained in
      controls of a similar age. RESULTS: Compared with controls, young children with
      MCT8 show choline and myoinositol level increases and N-acetyl aspartate
      decreases in supraventricular gray and white matter, phenomena associated with
      the degree of dysmyelinization according to MRI. CONCLUSION: MCT8 gene deficiency
      results in deviant myelinization and general atrophy, which is substantiated by
      the MR spectroscopy findings of increased choline and myoinositol levels and
      decreased N-acetyl aspartate. The observations suggest that different mutations
      in the MCT8 gene lead to differences in the severity of the clinical spectrum,
      dysmyelinization, and MR spectroscopy-detectable changes in brain metabolism.

PMID- 18319317
TI  - Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous
      versus systemic-venous graft drainage: impact on glucose regulatory hormones and
      the growth hormone/insulin-like growth factor-I axis.
AB  - CONTEXT: Pancreas grafts can be drained through the iliac vein (systemic
      drainage) or the portal vein. OBJECTIVE: We hypothesized that normalization of
      portal insulin in patients with portal pancreas graft drainage stimulates the
      GH/IGF-I axis and thereby contributes to glucose control. METHODS: We compared
      patients after combined kidney and pancreas transplantation with portal drainage
      (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and
      nondiabetic controls (n = 8). Overnight fasting sera were analyzed for free and
      total IGF-I and IGF-binding proteins. Glucose regulatory hormones were examined
      after an oral glucose tolerance test and GH after stimulation with GHRH. RESULTS:
      Systemic drainage led to higher basal and stimulated insulin levels than portal
      drainage (P < 0.05), but increments in response to oral glucose were reduced in
      both transplanted groups (P < 0.05 vs. controls). However, glucose tolerance was
      similar in all groups. Circulating free and total IGF-I and IGF-binding protein-3
      were similar to control levels in the systemic drainage group but elevated in the
      portal drainage group (P < 0.05). Consistently, the GH response was reduced in
      the portal drainage group (P < 0.05 vs. controls) and correlated inversely with
      free IGF-I (r = -0.63, P < 0.05). CONCLUSION: Portal drainage of pancreatic
      endocrine secretion in pancreas graft recipients raises IGF-I and lowers GH
      secretion. These changes might explain that glucose regulation is maintained
      despite lower peripheral insulin levels, compared with patients with systemic
      graft drainage and nondiabetic control subjects.

PMID- 18319318
TI  - Correlation among 25-hydroxy-vitamin D assays.
AB  - CONTEXT: Measurement of circulating 25-hydroxy-vitamin D [25(OH)D]) is the
      accepted clinical indicator of vitamin D status. However, between-laboratory
      differences in measurement of this analyte exist, which may confound clinical
      care. OBJECTIVES: We investigated the current agreement of 25(OH)D measurement in
      clinical laboratories and explored the possibility that simple calibration would
      improve between-laboratory agreement. DESIGN AND PARTICIPANTS: Serum obtained
      from healthy volunteers (age 20-60 yr) and one "calibrator," selected to have a
      25(OH)D value near 30 ng/ml, were sent for 25(OH)D measurement in four clinical
      laboratories (laboratories A-D) using HPLC, liquid chromatography tandem mass
      spectroscopy, and RIA methodologies. MAIN OUTCOME MEASURES: Serum 25(OH)D. Based
      upon self-report, the laboratory with the lowest interassay percent coefficient
      of variation was assigned as the reference to which the others were compared
      using linear regression and Bland-Altman analyses (Analyse-it; Analyse-it
      Software, Ltd., Leeds, UK). RESULTS: Good correlation was observed for 25(OH)D
      measurement between laboratory A and laboratories B-D (R(2) = 0.99, 0.81, and
      0.95, respectively). Modest between-laboratory variation was noted; the mean bias
      ranged from 2.9-5.2 ng/ml. Consistent with a systematic offset, each value in
      laboratory B was higher than in laboratory A, and 89% of values from laboratories
      B-D were higher than laboratory A. The use of a single calibrator and correction
      factor reduced mean between-laboratory bias for laboratories B and D.
      CONCLUSIONS: Measurement of 25(OH)D by clinical laboratories yields similar
      results. The use of even a single calibrator will improve, but not resolve,
      between-laboratory variability. Based upon these data, in combination with
      reported within-individual variability, we recommend that clinicians aim for
      values greater than 30 ng/ml in their patients.

PMID- 18319319
TI  - Visceral obesity and plasma glucose-insulin homeostasis: contributions of
      interleukin-6 and tumor necrosis factor-alpha in men.
AB  - OBJECTIVE: This study examined the relationships of two inflammatory cytokines,
      IL-6 and TNF-alpha, to visceral adiposity and indices of plasma glucose-insulin
      homeostasis. RESEARCH DESIGN AND METHODS: Plasma levels of IL-6 and TNF-alpha
      were measured in 189 untreated asymptomatic men (aged 43.7 +/- 7.8 yr; body mass
      index 29.0 +/- 4.3 kg/m(2); waist girth 98.6 +/- 10.3 cm). RESULTS: Significant
      and positive associations were found between both cytokines with adiposity and
      adipose tissue distribution indices (0.15 < or = r < 0.32; P < 0.05) as well as
      plasma glucose-insulin homeostasis variables (0.22 < or = r < 0.28; P <0.05).
      Comparison of two subgroups, each composed of 32 overweight men (> or =25
      kg/m(2)) with similar body mass index values (28.7 kg/m(2) in both groups) but
      with markedly different levels of visceral adipose tissue (< vs. > or = 130
      cm(2)), revealed significant differences only for IL-6 levels (1.42 +/- 1.15 vs.
      0.86 +/- 0.52 pg/ml; P < 0.02 for men with high vs. low visceral adipose tissue,
      respectively). Finally, when subjects were stratified on the basis of their
      respective concentrations of IL-6 and TNF-alpha (using the 50th percentile of
      their overall distribution), an ANOVA revealed an independent contribution of IL
      6 to the variation of fasting insulin (P < 0.01) and each of these two cytokines
      to the variation of insulin levels measured after a 75-g oral glucose challenge
      (P <0.01 for IL-6 and P < 0.05 for TNF-alpha). CONCLUSIONS: Because IL-6 appeared
      to be clearly associated with visceral adiposity, TNF-alpha rather showed
      associations with indices of total body fatness. Thus, TNF-alpha may contribute
      to the insulin resistance of overall obesity, whereas IL-6 may be one of the
      mediators of the hyperinsulinemic state specifically related to excess visceral
      adiposity.

PMID- 18319320
TI  - Insulin-induced gene 2 involvement in human adipocyte metabolism and body weight
      regulation.
AB  - BACKGROUND: Insulin-induced genes (INSIGs) encode proteins that block proteolytic
      activation of sterol regulatory element-binding proteins, transcription factors
      that regulate lipogenic enzymes, and adipocyte differentiation. OBJECTIVE: Here,
      we analyzed the relative significance of INSIG1 and INSIG2 in human liver and
      adipocyte metabolism, and defined a novel, functional polymorphism in the
      promoter of INSIG2 associated with body mass index. RESEARCH METHODS: Variations
      in gene expression of different human tissues, of hepatoma cells exposed to
      INSIG1 and INSIG2 gene silencing probes, and of differentiating 3T3-L1 adipocytes
      were determined by real-time quantitative PCR. The functional significance of a
      novel polymorphism in the promoter of INSIG2 was analyzed using in vitro methods
      and gene expression analysis of human adipose tissue, whereas the phenotype
      associated with this polymorphism was studied in two cohorts of middle-aged men.
      RESULTS: Gene expression analysis of 17 human tissues demonstrated that INSIG1 is
      highly expressed in the liver, whereas INSIG2 is ubiquitously expressed. Gene
      silencing experiments confirmed that INSIG1, but not INSIG2, regulates the
      expression of sterol regulatory element-binding proteins target genes in human
      hepatoma cells. In contrast, adipocyte differentiation of 3T3-L1 cells was
      associated with a 13-fold increase in expression of INSIG2. Significant
      relationships between the INSIG2-102G/A polymorphism and body mass index were
      observed in two cohorts of middle-aged men (ANOVA P = 0.017 and 0.044,
      respectively). In vitro studies and analysis of allele-specific expression in
      human adipose tissue substantiated the functional significance of the INSIG2
      102G/A polymorphism. CONCLUSION: INSIG2 is involved in adipocyte metabolism and
      body weight regulation.

PMID- 18319321
TI  - Differences between measurements of bone mineral densities by quantitative
      ultrasound and dual-energy X-ray absorptiometry in type 2 diabetic postmenopausal
      women.
AB  - CONTEXT: Quantitative ultrasound (QUS) may be more helpful than dual-energy X-ray
      absorptiometry (DXA) in detecting bone deficits in patients with type 2 diabetes
      mellitus (T2DM). OBJECTIVE: The objective of the study was to compare differences
      in bone mass measurement by DXA and QUS in T2DM and nondiabetic postmenopausal
      women. DESIGN, SETTING, AND PARTICIPANTS: This clinical investigation was a cross
      sectional study in 76 patients with T2DM and 86 nondiabetic postmenopausal women.
      MAIN OUTCOME MEASURES: The primary outcomes were speed of sound (SOS) at the
      radius, phalanx, and tibia measured by QUS and bone mineral density (BMD) at the
      lumbar spine (LS), femoral neck (FN), and total hip (TH) measured by DXA.
      RESULTS: BMDs in T2DM patients were higher (LS, 1.06 +/- 0.12 vs. 0.90 +/- 0.23
      g/cm(2); FN, 0.80 +/- 0.13 vs. 0.74 +/- 0.12 g/cm(2); TH, 0.87 +/- 0.14 vs. 0.80
      +/- 0.13 g/cm(2), respectively, P < 0.001), whereas SOSs were lower than those in
      nondiabetics (radius, 4044 +/- 178 vs. 4129 +/- 182 m/sec; phalanx, 3902 +/- 207
      vs. 3999 +/- 214 m/sec, respectively, P < 0.001). The positive relationships
      between SOS and BMD (r = 0.26-0.75, P < 0.05) in nondiabetics were not observed
      in women with T2DM. T2DM impacted negatively on SOSs (radius, beta= -0.223, P
      <0.01; phalanx, beta= -0.219, P <0.01) but positively on BMDs (LS, beta = 0.314,
      P < 0.001; FN, beta = 0.173, P < 0.05; TH, beta = 0.203, P <0.01). CONCLUSIONS:
      Differences in bone mass as measured by DXA and QUS in postmenopausal T2DM and
      nondiabetic women do not change in parallel. QUS can provide useful information
      in the skeletal assessment of patients with T2DM.

PMID- 18319322
TI  - Retinoic acid stimulation of the sodium/iodide symporter in MCF-7 breast cancer
      cells is mediated by the insulin growth factor-I/phosphatidylinositol 3-kinase
      and p38 mitogen-activated protein kinase signaling pathways.
AB  - CONTEXT: All-trans retinoic acid (tRA) induces differentiation in MCF-7 breast
      cancer cells, stimulates sodium/iodide symporter (NIS) gene expression, and
      inhibits cell proliferation. Radioiodine administration after systemic tRA
      treatment has been proposed as an approach to image and treat some differentiated
      breast cancer. OBJECTIVE: The objective of this work was to study the relative
      role of genomic and nongenomic pathways in tRA stimulation of NIS expression in
      MCF-7 cells. DESIGN: We inspected the human NIS gene locus for retinoic acid
      responsive elements and tested them for function. The effects of signal
      transduction pathway inhibitors were also tested in tRA-treated MCF-7 cells and
      TSH-stimulated FRTL-5 rat thyroid cells, followed by iodide uptake assay,
      quantitative RT-PCR of NIS, and cell cycle phase analysis. RESULTS: Multiple
      retinoic acid response elements around the NIS locus were identified by sequence
      inspection, but none of them was a functional tRA-induced element in MCF-7 cells.
      Inhibitors of the IGF-I receptor, Janus kinase, and phosphatidylinositol 3-kinase
      (PI3K), significantly reduced NIS mRNA expression and iodide uptake in tRA
      stimulated MCF-7 cells but not FRTL-5 cells. An inhibitor of p38 MAPK
      significantly reduced iodide uptake in both tRA-stimulated MCF-7 cells and TSH
      stimulated FRTL-5 cells. IGF-I and PI3K inhibitors did not significantly reduce
      the basal NIS mRNA expression in MCF-7 cells. Despite the chronic inhibitory
      effects on cell proliferation, tRA did not reduce the S-phase distribution of MCF
      7 cells during the period of NIS induction. CONCLUSION: The IGF-I receptor/PI3K
      pathway mediates tRA-stimulated NIS expression in MCF-7 but not FRTL-5 thyroid
      cells.

PMID- 18319323
TI  - Is a flexible mitral annuloplasty ring superior to a semi-rigid or rigid ring in
      terms of improvement in symptoms and survival?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether, in patients with mitral
      regurgitation secondary to degenerative mitral valve disease requiring mitral
      valve repair with an annuloplasty ring, a flexible ring is superior to a semi
      rigid or rigid ring in terms of improvement in symptoms and survival. Using the
      reported search 478 papers were identified. Twelve papers of which seven were
      echocardiographic studies and five clinical studies, including two randomised
      controlled trials (RCTs), represented the best evidence on the subject. The
      author, journal, date and country of publication, patient group studied, study
      type, relevant outcomes, results and study comments and weaknesses were tabulated
      for these. We conclude that current best available evidence suggests that, in
      patients with a flexible annuloplasty ring compared to patients with a semi
      rigid/rigid annuloplasty ring, the improvement in LV systolic function as
      reported by all the seven sophisticated echocardiographic studies with a total of
      266 patients does not translate into better clinical outcomes as five clinical
      studies with a total of 941 patients, including two RCTs, report comparable
      clinical outcomes for patients with mitral regurgitation secondary to
      degenerative mitral valve disease requiring mitral valve repair with an
      annuloplasty ring.

PMID- 18319324
TI  - Re-expansion pulmonary edema following video-assisted thoracic surgery for
      recurrent malignant pleural effusion.
AB  - A rare case of a unilateral re-expansion pulmonary edema following video-assisted
      thoracic surgery for malignant pleural effusion is described.

PMID- 18319325
TI  - Prediction of mortality in type 2 diabetes from health-related quality of life
      (ZODIAC-4).
AB  - OBJECTIVE: To investigate the relationship between health-related quality of life
      (HRQOL) and mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS: In 1998,
      1,143 primary care patients with type 2 diabetes participated in the Zwolle
      Outpatient Diabetes project Integrating Available Care (ZODIAC) study. At
      baseline, HRQOL was assessed with the RAND-36 and, after almost 6 years, life
      status was retrieved. Cox proportional hazards modeling was used to investigate
      the association between HRQOL (continuous data) and mortality with adjustment for
      selected confounders (smoking, age, sex, diabetes duration, A1C, renal function,
      BMI, blood pressure, HDL cholesterol, and macrovascular complications). RESULTS:
      The Physical Component Summary of the RAND-36 was inversely associated with
      mortality (hazard ratio [HR] 0.979 [95% CI 0.966-0.992]), as were two separate
      RAND-36 dimensions. CONCLUSIONS: This study found that HRQOL is an independent
      marker of mortality and emphasizes the importance of looking beyond clinical
      parameters in patients with type 2 diabetes.

PMID- 18319326
TI  - Serial measurements of cystatin C are more accurate than creatinine-based methods
      in detecting declining renal function in type 1 diabetes.
AB  - OBJECTIVE: Cystatin C-and creatinine-based methods were compared with (99m)
      technetium-diethylene-triamine-penta-acetic acid ((99m)Tc-DTPA) plasma clearance
      (isotopic glomerular filtration rate [iGFR]) for detecting declining renal
      function. RESEARCH DESIGN AND METHODS: Glomerular filtration rate (GFR) was
      monitored over a mean of 10.1 years in 85 subjects with type 1 diabetes (with an
      average of 5.6 measurements per individual). Baseline mean +/- SD iGFR of the
      cohort was 106.1 +/- 2.6 ml/min per 1.73 m(2). The rates of decline in GFR
      (DeltaGFR) were derived using linear regression. RESULTS: In 19 of 85 subjects
      with declining renal function (i.e., DeltaiGFR >3.3 ml/min per 1.73 m(2) per
      year), DeltaGFR (ml/min per 1.73 m(2) per year) was 6.5 by iGFR, 4.2 by
      10(4)/creatinine, 3.6 by Cockcroft-Gault formula, 3.4 by the Modification of Diet
      in Renal Disease (MDRD)-6 equation, and 3.5 by the MDRD-4 variable equation (P <
      0.01 vs. iGFR). In comparison, DeltaGFR was 6.1 using the formula Cys-GFR =
      (86.7/cystatin C concentration) - 4.2 (not significant). CONCLUSIONS: Cystatin C
      was more accurate in detecting decline in renal function than creatinine-based
      methods in this population of subjects with type 1 diabetes and a normal mean
      baseline GFR.

PMID- 18319327
TI  - Monoallele deletion of CBP leads to pericentromeric heterochromatin condensation
      through ESET expression and histone H3 (K9) methylation.
AB  - Chromatin remodeling is tightly controlled under physiological conditions.
      Alterations in chromatin structure are involved in the pathogenesis of neuronal
      systems. We found that the monoallelic deletion of CREB binding protein (CBP)
      results in the induction of ERG-associated protein with SET domain (ESET) and
      increases trimethylation of histone H3 (K9) and condensation of pericentromeric
      heterochromatin structure in neurons. Nested deletion and mutational analysis of
      the ESET promoter further demonstrated that the Ets-2 transcription factor
      regulates transcriptional activity of the ESET gene. In CBP+/- mice, Ets-2
      occupancy in the ESET promoter DNA was markedly elevated. Our results suggest
      that CBP is a transcriptional repressor of ESET gene expression by limiting Ets-2
      transcriptional activity, while CBP siRNA enhances basal and Ets-2-dependent ESET
      transcriptional activity. Altered expression of the ESET gene and
      hypertrimethylation of H3 (K9) correlate with striatal neuron atrophy and
      dysfunction in CBP+/- mice. These results establish an alternative pathway that
      loss of CBP leads to the pericentric heterochromatin condensation through ESET
      expression and trimethylation of H3 (K9).

PMID- 18319328
TI  - A regulatory variation in OPRK1, the gene encoding the kappa-opioid receptor, is
      associated with alcohol dependence.
AB  - Variations in OPRK1, which encodes the kappa-opioid receptor, are associated with
      the risk for alcohol dependence. Sequencing DNAs with higher and lower risk
      haplotypes revealed an insertion/deletion (indel) with a net addition of 830 bp
      located 1986 bp upstream of the translation start site (1389 bp upstream of the
      transcription start site). We demonstrated that the upstream region extending
      from -1647 to -10 bp or from -2312 to -10 bp (relative to the translation start
      site) could function as a promoter in transient transfection assays. We then
      determined that the presence of the indel reduced transcriptional activity by
      half. We used a PCR assay to genotype individuals in 219 multiplex alcohol
      dependent families of European American descent for the presence or absence of
      this indel. Family-based association analyses detected significant evidence of
      association of this insertion with alcoholism; the longer allele (with the
      indel), which had lower expression, is associated with higher risk for
      alcoholism. This indel is, therefore, a functional regulatory variation likely to
      explain at least part of the association of OPRK1 with alcohol dependence.

PMID- 18319329
TI  - Is sunlight important to melanoma causation?

PMID- 18319330
TI  - Are we overemphasizing sun avoidance in protection from melanoma?
AB  - The public health effect of melanoma in the United States is undeniable as
      approximately 60,000 diagnoses of invasive melanoma and 8,000 deaths from
      melanoma are expected in 2007. Due to the poor outcomes associated with treating
      advanced cases of melanoma, substantial public health resources have been devoted
      to prevention efforts. Of the various factors involved in the pathogenesis of
      melanoma, including genetic predisposition, immunosuppression, and UV radiation,
      decreasing UV exposure has attracted the most attention for decreasing the public
      health effect of melanoma. Although sun avoidance may be an important measure for
      reducing the public health effect of melanocytic and keratinocytic malignancies,
      educational and media campaigns to encourage sun avoidance have failed to achieve
      the desired behavior changes in young people, have had limited effect on elderly
      patients who have already experienced decades of damaging sun exposure, and most
      importantly have failed to decrease the incidence of melanoma. We believe the
      best method to reduce deaths from melanoma is to emphasize early detection and
      treatment of suspicious lesions through combined efforts of both patients and
      providers.

PMID- 18319331
TI  - Mitogen-activated protein kinase kinase signaling promotes growth and
      vascularization of fibrosarcoma.
AB  - We hypothesized that signaling through multiple mitogen-activated protein kinase
      (MAPK) kinase (MKK) pathways is essential for the growth and vascularization of
      soft-tissue sarcomas, which are malignant tumors derived from mesenchymal
      tissues. We tested this using HT-1080, NCI, and Shac fibrosarcoma-derived cell
      lines and anthrax lethal toxin (LeTx), a bacterial toxin that inactivates MKKs.
      Western blots confirmed that LeTx treatment reduced the levels of phosphorylated
      extracellular signal-regulated kinase and p38 MAPK in vitro. Although short
      treatments with LeTx only modestly affected cell proliferation, sustained
      treatment markedly reduced cell numbers. LeTx also substantially inhibited the
      extracellular release of angioproliferative factors including vascular
      endothelial growth factor, interleukin-8, and basic fibroblast growth factor.
      Similar results were obtained with cell lines derived from malignant fibrous
      histiocytomas, leiomyosarcomas, and liposarcomas. In vivo, LeTx decreased MAPK
      activity and blocked fibrosarcoma growth. Growth inhibition correlated with
      decreased cellular proliferation and extensive necrosis, and it was accompanied
      by a decrease in tumor mean vessel density as well as a reduction in serum
      expression of angioproliferative cytokines. Vital imaging using high-resolution
      ultrasound enhanced with contrast microbubbles revealed that the effects of LeTx
      on tumor perfusion were remarkably rapid (<24 h) and resulted in a marked
      reduction of perfusion within the tumor but not in nontumor tissues. These
      results are consistent with our initial hypothesis and lead us to propose that
      MKK inhibition by LeTx is a broadly effective strategy for targeting
      neovascularization in fibrosarcomas and other similar proliferative lesions.

PMID- 18319332
TI  - Targeted drug delivery to mesothelioma cells using functionally selected
      internalizing human single-chain antibodies.
AB  - Mesothelioma is a malignancy of the mesothelium and current treatments are
      generally ineffective. One promising area of anticancer drug development is to
      explore tumor susceptibility to targeted therapy. To achieve efficient, targeted
      intracellular delivery of therapeutic agents to mesothelioma cells, we selected a
      naive human single-chain (scFv) phage antibody display library directly on the
      surface of live mesothelioma cells to identify internalizing antibodies that
      target mesothelioma-associated cell surface antigens. We have identified a panel
      of internalizing scFvs that bind to mesothelioma cell lines derived from both
      epithelioid (M28) and sarcomatous (VAMT-1) types of this disease. Most
      importantly, these antibodies stain mesothelioma cells in situ and therefore
      define a panel of clinically represented tumor antigens. We have further
      exploited the internalizing function of these scFvs to achieve targeted
      intracellular drug delivery to mesothelioma cells. We showed that scFv-targeted
      immunoliposomes were efficiently and specifically taken up by both epithelioid
      and sarcomatous mesothelioma cells, but not control cells, and immunoliposomes
      encapsulating the small-molecule drug topotecan caused targeted killing of both
      types of mesothelioma cells in vitro.

PMID- 18319333
TI  - Ellipticine derivative NSC 338258 represents a potential new antineoplastic agent
      for the treatment of multiple myeloma.
AB  - High-risk multiple myeloma can be correlated with amplification and
      overexpression of the cell cycle regulator CKS1B. Herein, we used the COMPARE
      algorithm to correlate high expression of CKS1B mRNA in the NCI-60 cell line
      panel with the concentration causing 50% growth inhibition (GI(50)) of >40,000
      synthetic compounds. This led to the identification of NSC 338258 (EPED3), a
      highly stable, hydrophilic derivative of the plant alkaloid ellipticine. In
      vitro, this synthetic anticancer compound exhibits dramatic cytotoxic activity
      against myeloma cells grown in suspension or in coculture with stromal cells.
      EPED3-induced cell cycle arrest and an apoptotic progression that appear to be a
      consequence of the instantaneous effect of the drug on cytoplasmic organelles,
      particularly mitochondria. Disruption of mitochondria and cytoplasmic
      distribution of cytochrome c initiated the intracellular proteolytic cascade
      through the intrinsic apoptotic pathway. EPED3 is able to induce apoptosis in
      myeloma cells with de novo or acquired resistance to commonly administered
      antimyeloma agents. Collectively, our data suggest that EPED3 targets
      mitochondrial function to rapidly deplete chemical energy and initiate apoptosis
      in myeloma cells at nanomolar concentrations while leaving stromal cells
      unharmed.

PMID- 18319334
TI  - Level of HER-2/neu protein expression in breast cancer may affect the development
      of endogenous HER-2/neu-specific immunity.
AB  - We questioned whether the incidence or magnitude of the humoral or cellular
      immune response to the self-tumor antigen HER-2/neu is influenced by the level of
      HER-2/neu protein overexpression as defined by immunohistochemical staining of
      tumors in breast cancer patients. We obtained peripheral blood from 104 women
      with stage II, III, and IV pathologically confirmed HER-2/neu-overexpressing
      breast cancer. Patients were categorized with +1 (n = 14), +2 (n = 20), or +3 (n
      = 70) HER-2/neu overexpression by institutional pathologic report. Circulating
      antibodies to HER-2/neu were evaluated using ELISA. T-cell responses to HER-2/neu
      were measured using an antigen-specific tritiated thymidine incorporation assay.
      Eighty-two percent of subjects with HER-2/neu antibodies were +3 overexpressors
      compared with 18% +2 overexpressors and 0% +1 overexpressors, a highly
      significant difference (P < 0.001), and there were significant differences in the
      magnitude of the HER-2/neu-specific antibodies between groups with varying HER
      2/neu protein expression (P = 0.022). In addition, 65% of subjects with HER-2/neu
      specific T cells were +3 overexpressors compared with 16% +2 overexpressors and
      19% +1 overexpressors (P = 0.001). Data presented here indicate that endogenous
      HER-2/neu-specific humoral and T-cell immunity is greater in patients with +3
      protein overexpression in their tumors than in patients with lower levels of HER
      2/neu expression. Overexpression of a self-tumor-associated protein is a
      potential mechanism by which immunogenicity is enhanced and may aid in the
      identification of biologically relevant proteins to target for immune-based
      molecular cancer therapies.

PMID- 18319335
TI  - Modulation of drug resistance by artificial transcription factors.
AB  - The efficiency of chemotherapeutic treatments in cancer patients is often
      impaired by the acquisition of drug resistance. Cancer cells develop drug
      resistance through dysregulation of one or more genes or cellular pathways. To
      isolate efficient regulators of drug resistance in tumor cells, we have adopted a
      genome-wide scanning approach based on the screening of large libraries of
      artificial transcription factors (ATFs) made of three and six randomly assembled
      zinc finger domains. Zinc finger libraries were linked to a VP64 activation
      domain and delivered into a paclitaxel-sensitive tumor cell line. Following drug
      treatment, several ATFs were isolated that promoted drug resistance. One of these
      ATFs, 3ZF-1-VP, promoted paclitaxel resistance in cell lines having mutated or
      inactivated p53, such as MDA-MB-435 and Kaposi's sarcoma cell lines. 3ZF-1-VP
      also induced strong resistance to etoposide, vincristine, and cisplatinum.
      Linkage of a repression domain to the selected ATF resulted in enhanced
      sensitivity to multiple drugs, particularly vincristine, cisplatinum, and 5
      fluorouracil. Small interfering RNA-mediated inhibition of p53 revealed that 3ZF
      1-VP activated both p53-dependent and p53-independent mechanisms to promote
      survival, whereas other ATF required intact p53. Real-time expression analysis
      and DNA microarrays showed that several ATFs up-regulated targets of p53, such as
      the cyclin-dependent kinase inhibitor p21(WAF1/CIP1), and genes participating in
      the p14(ARF)-MDM2-p53 tumor suppressor pathway, such as hDMP1. Thus, ATF can be
      used to map genes and pathways involved in drug resistance phenotypes and have
      potential as novel therapeutic agents to inhibit drug resistance.

PMID- 18319336
TI  - Opening and closing of the periplasmic gate in lactose permease.
AB  - X-ray crystal structures of lactose permease (LacY) reveal pseudosymmetrically
      arranged N- and C-terminal six-transmembrane helix bundles surrounding a deep
      internal cavity open on the cytoplasmic side and completely closed on the
      periplasmic side. The residues essential for sugar recognition and H(+)
      translocation are located at the apex of the cavity and are inaccessible from the
      outside. On the periplasmic side, helices I/II and VII from the N- and C- six
      helix bundles, respectively, participate in sealing the cavity from the outside.
      Three paired double-Cys mutants-Ile-40 --> Cys/Asn-245 --> Cys, Thr-45 -->
      Cys/Asn-245 --> Cys, and Ile-32 --> Cys/Asn-245 --> Cys-located in the interface
      between helices I/II and VII on the periplasmic side of LacY were constructed.
      After cross-linking with homobifunctional reagents less than approximately 15 A
      in length, all three mutants lose the ability to catalyze lactose transport.
      Strikingly, however, full or partial activity is observed when cross-linking is
      mediated by flexible reagents greater than approximately 15 A in length. The
      results provide direct support for the argument that transport via LacY involves
      opening and closing of a large periplasmic cavity.

PMID- 18319337
TI  - Leishmania requires Rab7-mediated degradation of endocytosed hemoglobin for their
      growth.
AB  - Leishmania is unable to synthesize heme and must acquire it from exogenous
      source, the mechanism of which is not known. We have shown that Leishmania
      endocytoses hemoglobin (Hb) and subsequently degrade it probably to generate
      heme. To understand how internalized Hb is degraded, we have cloned and expressed
      Rab7 homolog from Leishmania donovani. Interestingly, Rab7 in Leishmania is found
      to be localized both on early and late endocytic compartment and regulates both
      uptake and degradation of endocytosed Hb demonstrating that Rab7 in Leishmania
      play a very unique role connecting both early and late events of Hb endocytosis.
      Our data also indicate that overexpression of Rab7:WT in Leishmania induces
      transport of Hb to lysosomes and rapidly degrade internalized Hb. Whereas Hb
      transport to lysosomes and its degradation is significantly inhibited in cells
      overexpressing Rab7:T21N, a GDP locked mutant of Rab7. Moreover, cells
      overexpressing Rab7:T21N grow at a slower rate (<50%) compared with control
      Leishmania. Addition of exogenous hemin recovers the growth of Rab7:T21N mutant
      cells almost to the control level, suggesting that intracellular heme generated
      by Rab7-mediated Hb degradation is required for optimal growth of the parasites.
      Thus, our results identify a potential target which might be exploited to
      suppress the growth of Leishmania.

PMID- 18319338
TI  - Elephant shark sequence reveals unique insights into the evolutionary history of
      vertebrate genes: A comparative analysis of the protocadherin cluster.
AB  - Cartilaginous fishes are the oldest living phylogenetic group of jawed
      vertebrates. Here, we demonstrate the value of cartilaginous fish sequences in
      reconstructing the evolutionary history of vertebrate genomes by sequencing the
      protocadherin cluster in the relatively small genome (910 Mb) of the elephant
      shark (Callorhinchus milii). Human and coelacanth contain a single protocadherin
      cluster with 53 and 49 genes, respectively, that are organized in three
      subclusters, Pcdhalpha, Pcdhbeta, and Pcdhgamma, whereas the duplicated
      protocadherin clusters in fugu and zebrafish contain >77 and 107 genes,
      respectively, that are organized in Pcdhalpha and Pcdhgamma subclusters. By
      contrast, the elephant shark contains a single protocadherin cluster with 47
      genes organized in four subclusters (Pcdhdelta, Pcdhepsilon, Pcdhmu, and Pcdhnu).
      By comparison with elephant shark sequences, we discovered a Pcdhdelta subcluster
      in teleost fishes, coelacanth, Xenopus, and chicken. Our results suggest that the
      protocadherin cluster in the ancestral jawed vertebrate contained more
      subclusters than modern vertebrates, and the evolution of the protocadherin
      cluster is characterized by lineage-specific differential loss of entire
      subclusters of genes. In contrast to teleost fish and mammalian protocadherin
      genes that have undergone gene conversion events, elephant shark protocadherin
      genes have experienced very little gene conversion. The syntenic block of genes
      in the elephant shark protocadherin locus is well conserved in human but
      disrupted in fugu. Thus, the elephant shark genome appears to be less prone to
      rearrangements compared with teleost fish genomes. The small and "stable" genome
      of the elephant shark is a valuable reference for understanding the evolution of
      vertebrate genomes.

PMID- 18319339
TI  - Unmodified self antigen triggers human CD8 T cells with stronger tumor reactivity
      than altered antigen.
AB  - Human cancer vaccines are often prepared with altered "analog" or "heteroclitic"
      antigens that have been optimized for HLA class I binding, resulting in enhanced
      immunogenicity. Here, we take advantage of CpG oligodeoxynucleotides as powerful
      vaccine adjuvants and demonstrate the induction of high T cell frequencies in
      melanoma patients, despite the use of natural (unmodified) tumor antigenic
      peptide. Compared with vaccination with analog peptide, natural peptide induced T
      cell frequencies that were approximately twofold lower. However, T cells showed
      superior tumor reactivity because of (i) increased functional avidity for natural
      antigen and (ii) enhancement of T cell activation and effector function. Thus,
      novel vaccine formulations comprising potent immune stimulators may allow to
      circumvent the need for modified antigens and can induce highly functional T
      cells with precise antigen specificity.

PMID- 18319340
TI  - Micro- and nanoparticles self-assembly for virtually defect-free, adjustable
      monolayers.
AB  - As chips further shrink toward smaller scales, fabrication processes based on the
      self-assembly of individual particles into patterns or structures are often
      sought. One of the most popular techniques for two-dimensional assembly (self
      assembled monolayers) is based on capillary forces acting on particles placed at
      a liquid interface. Capillarity-induced clustering, however, has several
      limitations: it applies to relatively large (radius > approximately 10 microm)
      particles only, the clustering is usually non-defect-free and lacks long-range
      order, and the lattice spacing cannot be adjusted. The goal of the present
      article is to show that these shortcomings can be addressed by using an external
      electric field normal to the interface. The resulting self-assembly is capable of
      controlling the lattice spacing statically or dynamically, forming virtually
      defect-free monolayers, and manipulating a broad range of particle sizes and
      types including nanoparticles and electrically neutral particles.

PMID- 18319341
TI  - A nanostructure-initiator mass spectrometry-based enzyme activity assay.
AB  - We describe a Nanostructure-Initiator Mass Spectrometry (NIMS) enzymatic
      (Nimzyme) assay in which enzyme substrates are immobilized on the mass
      spectrometry surface by using fluorous-phase interactions. This "soft"
      immobilization allows efficient desorption/ionization while also enabling the use
      of surface-washing steps to reduce signal suppression from complex biological
      samples, which results from the preferential retention of the tagged products and
      reactants. The Nimzyme assay is sensitive to subpicogram levels of enzyme,
      detects both addition and cleavage reactions (sialyltransferase and
      galactosidase), is applicable over a wide range of pHs and temperatures, and can
      measure activity directly from crude cell lysates. The ability of the Nimzyme
      assay to analyze complex mixtures is illustrated by identifying and directly
      characterizing beta-1,4-galactosidase activity from a thermophilic microbial
      community lysate. The optimal enzyme temperature and pH were found to be 65
      degrees C and 5.5, respectively, and the activity was inhibited by both
      phenylethyl-beta-d-thiogalactopyranoside and deoxygalactonojirimycin. Metagenomic
      analysis of the community suggests that the activity is from an uncultured,
      unsequenced gamma-proteobacterium. In general, this assay provides an efficient
      method for detection and characterization of enzymatic activities in complex
      biological mixtures prior to sequencing or cloning efforts. More generally, this
      approach may have important applications for screening both enzymatic and
      inhibitor libraries, constructing and screening glycan microarrays, and
      complementing fluorous-phase organic synthesis.

PMID- 18319342
TI  - Simultaneous in vivo positron emission tomography and magnetic resonance imaging.
AB  - Positron emission tomography (PET) and magnetic resonance imaging (MRI) are
      widely used in vivo imaging technologies with both clinical and biomedical
      research applications. The strengths of MRI include high-resolution, high
      contrast morphologic imaging of soft tissues; the ability to image physiologic
      parameters such as diffusion and changes in oxygenation level resulting from
      neuronal stimulation; and the measurement of metabolites using chemical shift
      imaging. PET images the distribution of biologically targeted radiotracers with
      high sensitivity, but images generally lack anatomic context and are of lower
      spatial resolution. Integration of these technologies permits the acquisition of
      temporally correlated data showing the distribution of PET radiotracers and MRI
      contrast agents or MR-detectable metabolites, with registration to the underlying
      anatomy. An MRI-compatible PET scanner has been built for biomedical research
      applications that allows data from both modalities to be acquired simultaneously.
      Experiments demonstrate no effect of the MRI system on the spatial resolution of
      the PET system and <10% reduction in the fraction of radioactive decay events
      detected by the PET scanner inside the MRI. The signal-to-noise ratio and
      uniformity of the MR images, with the exception of one particular pulse sequence,
      were little affected by the presence of the PET scanner. In vivo simultaneous PET
      and MRI studies were performed in mice. Proof-of-principle in vivo MR
      spectroscopy and functional MRI experiments were also demonstrated with the
      combined scanner.

PMID- 18319343
TI  - Inhibition of midkine alleviates experimental autoimmune encephalomyelitis
      through the expansion of regulatory T cell population.
AB  - CD4(+)CD25(+) regulatory T (Treg) cells are crucial mediators of autoimmune
      tolerance. The factors that regulate Treg cells, however, are largely unknown.
      Here, we show that deficiency in midkine (MK), a heparin-binding growth factor
      involved in oncogenesis, inflammation, and tissue repair, attenuated experimental
      autoimmune encephalomyelitis (EAE) because of an expansion of the Treg cell
      population in peripheral lymph nodes and decreased numbers of autoreactive T
      helper type 1 (T(H)1) and T(H)17 cells. MK decreased the Treg cell population ex
      vivo in a dose-dependent manner by suppression of STAT5 phosphorylation that is
      essential for Foxp3 expression. Moreover, administration of anti-MK RNA aptamers
      significantly expanded the Treg cell population and alleviated EAE symptoms.
      These observations indicate that MK serves as a critical suppressor of Treg cell
      expansion, and inhibition of MK using RNA aptamers may provide an effective
      therapeutic strategy against autoimmune diseases, including multiple sclerosis.

PMID- 18319344
TI  - Analyses of Mlc-IIBGlc interaction and a plausible molecular mechanism of Mlc
      inactivation by membrane sequestration.
AB  - In Escherichia coli, glucose-dependent transcriptional induction of genes
      encoding a variety of sugar-metabolizing enzymes and transport systems is
      mediated by the phosphorylation state-dependent interaction of membrane-bound
      enzyme IICB(Glc) (EIICB(Glc)) with the global repressor Mlc. Here we report the
      crystal structure of a tetrameric Mlc in a complex with four molecules of enzyme
      IIB(Glc) (EIIB), the cytoplasmic domain of EIICB(Glc). Each monomer of Mlc has
      one bound EIIB molecule, indicating the 1:1 stoichiometry. The detailed view of
      the interface, along with the high-resolution structure of EIIB containing a
      sulfate ion at the phosphorylation site, suggests that the phosphorylation
      induced steric hindrance and disturbance of polar intermolecular interactions
      impede complex formation. Furthermore, we reveal that Mlc possesses a built-in
      flexibility for the structural adaptation to its target DNA and that interaction
      of Mlc with EIIB fused only to dimeric proteins resulted in the loss of its DNA
      binding ability, suggesting that flexibility of the Mlc structure is
      indispensable for its DNA binding.

PMID- 18319345
TI  - Regulation of surface architecture by symbiotic bacteria mediates host
      colonization.
AB  - Microbes occupy countless ecological niches in nature. Sometimes these
      environments may be on or within another organism, as is the case in both
      microbial infections and symbiosis of mammals. Unlike pathogens that establish
      opportunistic infections, hundreds of human commensal bacterial species establish
      a lifelong cohabitation with their hosts. Although many virulence factors of
      infectious bacteria have been described, the molecular mechanisms used during
      beneficial host-symbiont colonization remain almost entirely unknown. The novel
      identification of multiple surface polysaccharides in the important human
      symbiont Bacteroides fragilis raised the critical question of how these molecules
      contribute to commensalism. To understand the function of the bacterial capsule
      during symbiotic colonization of mammals, we generated B. fragilis strains
      deleted in the global regulator of polysaccharide expression and isolated mutants
      with defects in capsule expression. Surprisingly, attempts to completely
      eliminate capsule production are not tolerated by the microorganism, which
      displays growth deficits and subsequent reversion to express capsular
      polysaccharides. We identify an alternative pathway by which B. fragilis is able
      to reestablish capsule production and modulate expression of surface structures.
      Most importantly, mutants expressing single, defined surface polysaccharides are
      defective for intestinal colonization compared with bacteria expressing a
      complete polysaccharide repertoire. Restoring the expression of multiple capsular
      polysaccharides rescues the inability of mutants to compete for commensalism.
      These findings suggest a model whereby display of multiple capsular
      polysaccharides provides essential functions for bacterial colonization during
      host-symbiont mutualism.

PMID- 18319346
TI  - Snowboarding and ski boarding injuries in Niigata, Japan.
AB  - BACKGROUND: The purpose of this study was to compare the injury patterns and
      incidence of snowboarding and ski boarding injuries with that of alpine skiing in
      2000 to 2005, as there are few previous studies comparing these 3 sports,
      especially in Asia. HYPOTHESIS: The injury patterns are different among the 3
      snow sports. STUDY DESIGN: Descriptive epidemiology study. METHODS: The subjects
      were alpine skiers (1240 cases), snowboarders (2220 cases), and ski boarders (132
      cases) who were injured in 2 ski resorts located in Niigata prefecture in Japan
      and visited the authors' clinics in these ski resorts between 2000 and 2005. On
      visiting the clinics, patients completed a questionnaire reviewing the
      circumstances surrounding the injury event, and physicians documented the
      diagnosis. RESULTS: The injury rate, which was based on all purchased lift
      tickets, in snowboarding decreased gradually, although it was still 2 times
      higher than that of alpine skiing. Snowboarding and ski boarding had a higher
      fracture and dislocation rate. Both sports also had a 4 times higher rate of
      injuries because of jumping. The characteristics of ski boarding were a lower
      head and neck injury rate and collision injury rate than those of the other 2
      snow sports, as well as a 2 times higher rate of fractures compared with alpine
      skiing injuries and a 1.4 times higher incidence than that of snowboarding
      injuries. Of the fractures caused by ski boarding accidents, 39.6% affected the
      lower leg bones. CONCLUSION: Injury prevention strategies should focus on jumps
      for snowboarders and ski boarders.

PMID- 18319347
TI  - Shoulder strength after open versus arthroscopic stabilization.
AB  - BACKGROUND: With current techniques, the main difference between arthroscopic and
      open shoulder stabilization is the violation of the subscapularis tendon. No
      studies have looked at strength differences of internal and external rotation
      between these groups. HYPOTHESIS: Internal rotation strength deficits will exist
      in patients having undergone an open shoulder stabilization procedure compared
      with an arthroscopic one. STUDY DESIGN: Piggy-back randomized controlled trial;
      Level of evidence, 1. METHODS: Forty-eight patients (38 men, 10 women), average
      age, 30.6 years (range, 18-59 years), were randomized to either open (n = 24) or
      arthroscopic (n = 24) shoulder stabilization. Rehabilitation protocols were
      standardized. At a mean follow-up of 19.4 months (range, 12-36 months) from
      surgery, patients underwent isokinetic strength testing (concentric and eccentric
      peak moments at 60 deg/s and 180 deg/s). Measurements were body-mass normalized.
      Primary outcome was internal rotation strength at 60 deg/s. RESULTS: There were
      no significant differences between groups with respect to age, gender, or
      operative limb. There were no statistical differences between operative groups
      for the primary outcome of internal concentric strength at 60 deg/s (mean
      difference, 0.011 N.m/kg; 95% confidence interval, -0.043 to 0.066; P = .677) or
      secondary strength measures. When compared with the contralateral limb, strength
      deficits existed for both surgical groups for both internal and external
      rotation. Regression analysis demonstrated that arm dominance is a factor in
      strength deficits. CONCLUSION: The results of this trial suggest there are no
      side-to-side isokinetic strength deficits between patients having an open
      stabilization using a subscapularis splitting approach versus arthroscopic
      stabilization for anterior traumatic shoulder instability at 1 year after
      surgery. Strength deficits exist in both groups when compared with the
      contralateral limb.

PMID- 18319348
TI  - Augmentation of tendon-to-bone healing with a magnesium-based bone adhesive.
AB  - BACKGROUND: Healing of an anterior cruciate ligament graft in a bone tunnel
      occurs by formation of fibrous scar tissue, which is weaker than the normal
      fibrocartilaginous insertion. HYPOTHESIS: We hypothesized that a magnesium-based
      bone adhesive would improve tendon-to-bone healing in a rabbit anterior cruciate
      ligament reconstruction model. STUDY DESIGN: Controlled laboratory study.
      METHODS: Thirty-five New Zealand White rabbits underwent bilateral anterior
      cruciate ligament reconstructions with semitendinosus autografts. A total of 12.5
      g of bone adhesive was placed in the intraosseous tunnel around the graft in one
      limb, while the tunnels in the contralateral limb received no implant. Sixteen
      animals each were sacrificed at 3 weeks and at 6 weeks (12 biomechanical
      testing/4 histology). Outcomes included semiquantitative histologic analyses for
      new cartilage formation and fibrous tissue formation in the tendon-bone
      interface, microcomputed tomography to quantify new bone formation along the bone
      tunnel, and biomechanical testing of load-to-failure and stiffness. Three animals
      were sacrificed at time 0 to confirm adequate tunnel fill with the bone adhesive
      on microcomputed tomography. RESULTS: All specimens had adequate tunnel fill with
      the bone adhesive at time 0. Application of the bone adhesive resulted in more
      cartilage formation and less fibrous tissue formation at the tendon-bone
      interface at 6 weeks compared with controls (P < .05). There was significantly
      more bone formation in the tibia of the treated limbs at 6 weeks (P = .01). The
      load-to-failure was significantly higher in the treated group at 6 weeks (71.8 +/
      31.8 N vs 43.4 +/- 14.8 N; P = .04). There were no differences in stiffness at
      either time point, and there were no differences at 3 weeks in any outcome
      variable. CONCLUSION: The magnesium-based bone adhesive improves tendon-to-bone
      healing based on histologic and biomechanical testing at 6 weeks in a rabbit
      model of anterior cruciate ligament reconstruction. CLINICAL RELEVANCE: Further
      studies are needed to investigate the clinical potential of this bone adhesive to
      enhance healing and decrease recovery time in soft-tissue ligament
      reconstruction.

PMID- 18319349
TI  - Complete proximal hamstring avulsions: a series of 41 patients with operative
      treatment.
AB  - BACKGROUND: Complete proximal hamstring avulsions can cause considerable
      morbidity and are often associated with significant functional loss. HYPOTHESIS:
      Early surgical treatment leads to better results than does surgery in the chronic
      phase. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Forty-one
      patients (21 men and 20 women) with a complete proximal hamstring avulsion were
      included. The cases were retrospectively analyzed, and a 4-category rating system
      was used to evaluate the overall result of the surgical treatment. RESULTS: The
      mean follow-up was 37 months (range, 12-72 months). Nineteen patients were rated
      as having an excellent result and 10 patients a good result. In 5 patients, the
      result was classified as moderate and in 7 patients poor. In the patients with an
      excellent or good result, the delay from the injury to surgery averaged 2.4
      months, whereas in patients with a moderate or poor result, the delay averaged
      11.7 months. The difference was statistically significant (P < .001). CONCLUSION:
      Excellent or good results can often be expected with surgery, and considerable
      improvement of symptoms may be achieved even in chronic cases. According to the
      results, early operative treatment in complete proximal avulsions of the
      hamstring muscles gives better results than does late surgery and is therefore
      recommended.

PMID- 18319350
TI  - The addition of rotator interval closure after arthroscopic repair of either
      anterior or posterior shoulder instability: effect on glenohumeral translation
      and range of motion.
AB  - BACKGROUND: Although the use of rotator interval closure is frequently advocated
      as a useful supplement to shoulder instability repairs, the addition of a rotator
      interval closure after arthroscopic instability repair has not been fully
      investigated. PURPOSE: The objective of this study was to investigate whether a
      rotator interval closure improves glenohumeral stability in an anterior and
      posterior instability shoulder model. STUDY DESIGN: Controlled laboratory study.
      METHODS: Fourteen fresh-frozen cadaveric shoulder specimens were dissected free
      of soft tissues, leaving the rotator cuff intact with simulated cuff loading. All
      specimens were mounted in a custom testing apparatus using infrared sensors to
      document glenohumeral translation and rotation. The specimens were then tested
      for stability in the following order: vented/subluxated state, after arthroscopic
      anterior (Group 1; 7 specimens) or posterior (Group 2; 7 specimens) instability
      repair with suture anchors, and then after rotator interval closure. For each of
      the 3 testing conditions, the following were measured: (1) external and internal
      rotation at neutral, (2) external and internal rotation at 90 degrees of
      abduction, (3) posterior and anterior translation at neutral rotation (15 N and
      25 N), (4) anterior translation at 90 degrees of abduction and external rotation
      (Group 1; 15 N and 25 N), (5) posterior translation at 90 degrees of flexion and
      internal rotation (Group 2; 15 N and 25 N), and (6) sulcus testing in neutral
      (7.5 N). RESULTS: Posterior stability was only improved after anchor
      capsulolabral repair (8.0 to 5.0 mm; P = .017, 25 N), but there was no
      improvement after rotator interval closure (5.0 to 4.6 mm; P = .453). However,
      anterior stability was improved after capsulolabral repair (8.6 to 4.0 mm; P =
      .016, 25 N) and also improved further by rotator interval closure (4.0 to 2.4 mm;
      P = .007). The mean loss of external rotation was significantly increased by the
      addition of the rotator interval closure in both neutral and abducted
      glenohumeral positions, with a mean external rotation loss of 28 degrees in
      neutral (P = .013). The addition of a rotator interval closure did not improve
      sulcus stability (P = .4). CONCLUSION: The addition of an arthroscopic rotator
      interval closure after posterior capsulolabral repair did not improve posterior
      stability; however, anterior stability was improved further after a rotator
      interval closure. Inferior stability was not improved. Arthroscopic rotator
      interval closure significantly decreased external rotation at both neutral and
      abducted arm positions. CLINICAL RELEVANCE: Arthroscopic closure may be
      beneficial in certain cases of anterior shoulder instability; however, posterior
      instability was not improved. Predictable losses of external rotation after
      rotator interval closure are of concern.

PMID- 18319351
TI  - Arthroscopic repair of isolated meniscal tears in patients 18 years and younger.
AB  - BACKGROUND: Isolated meniscal tears in the skeletally immature patient are
      infrequent but well-recognized injuries. Although few studies have evaluated the
      pediatric and adolescent population, arthroscopic surgical repair remains the
      standard of care for patients in this age group with unstable meniscal tears.
      PURPOSE: To review our results of arthroscopic repair of isolated meniscal tears
      in pediatric and adolescent patients to further define future management of these
      injuries. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The records
      of all patients 18 years old or younger who underwent isolated meniscal repair
      between 1990 and 2005 were retrospectively reviewed. Forty-four patients (6
      girls, 38 boys) with an average age of 15.8 years (range, 9.9-18.7 years) were
      included in this study, for a total of 45 isolated meniscal tears. Clinical
      examinations were performed, International Knee Documentation Committee forms
      were administered, and Tegner scores were determined at an average of 5.8 years
      (range, 2.5 months-13.8 years) postoperative follow-up. Three patients were lost
      to follow-up. RESULTS: The clinical success rate of arthroscopic meniscal repair
      was 80% for simple tears, 68% for displaced bucket-handle tears, and 13% for
      complex tears. Seventeen menisci (38% overall) failed initial repair at a mean of
      17 months (range, 3-61 months) postoperatively and underwent repeat arthroscopic
      surgery (15 partial meniscectomies, 2 rerepair). The average Tegner and
      International Knee Documentation Committee scores were 8 (range, 5-9) and 89.4
      (range, 79-99), respectively, at the time of final follow-up. Risk factors for
      failure included complex tears and rim width greater than 3 mm. CONCLUSION:
      Clinically successful repair of an isolated meniscal tear in patients 18 years or
      younger was variable depending on tear type, with complex tears and rim width 3
      mm or greater being negative prognostic factors.

PMID- 18319352
TI  - Exercise-induced alterations in intramyocellular lipids and insulin resistance:
      the athlete's paradox revisited.
AB  - We previously reported an "athlete's paradox" in which endurance-trained
      athletes, who possess a high oxidative capacity and enhanced insulin sensitivity,
      also have higher intramyocellular lipid (IMCL) content. The purpose of this study
      was to determine whether moderate exercise training would increase IMCL,
      oxidative capacity of muscle, and insulin sensitivity in previously sedentary
      overweight to obese, insulin-resistant, older subjects. Twenty-five older (66.4
      +/- 0.8 yr) obese (BMI = 30.3 +/- 0.7 kg/m2) men (n = 9) and women (n = 16)
      completed a 16-wk moderate but progressive exercise training program. Body weight
      and fat mass modestly but significantly (P < 0.01) decreased. Insulin
      sensitivity, measured using the euglycemic hyperinsulinemic clamp, was increased
      (21%, P = 0.02), with modest improvements (7%, P = 0.04) in aerobic fitness
      (Vo2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative
      capacity [succinate dehydrogenase activity (SDH)], glycogen content, capillary
      density, and fiber type were performed on skeletal muscle biopsies. Exercise
      training increased IMCL by 21%. In contrast, diacylglycerol and ceramide,
      measured by mass spectroscopy, were decreased (n = 13; -29% and -24%,
      respectively, P < 0.05) with exercise training. SDH (19%), glycogen content
      (15%), capillary density (7%), and the percentage of type I slow oxidative fibers
      (from 50.8 to 55.7%), all P < or = 0.05, were increased after exercise. In
      summary, these results extend the athlete's paradox by demonstrating that chronic
      exercise in overweight to obese older adults improves insulin sensitivity in
      conjunction with favorable alterations in lipid partitioning and an enhanced
      oxidative capacity within muscle. Therefore, several key deleterious effects of
      aging and/or obesity on the metabolic profile of skeletal muscle can be reversed
      with only moderate increases in physical activity.

PMID- 18319353
TI  - Uteroplacental insufficiency and reducing litter size alters skeletal muscle
      mitochondrial biogenesis in a sex-specific manner in the adult rat.
AB  - Uteroplacental insufficiency has been shown to impair insulin action and glucose
      homeostasis in adult offspring and may act in part via altered mitochondrial
      biogenesis and lipid balance in skeletal muscle. Bilateral uterine vessel
      ligation to induce uteroplacental insufficiency in offspring (Restricted) or sham
      surgery was performed on day 18 of gestation in rats. To match the litter size of
      Restricted offspring, a separate cohort of sham litters had litter size reduced
      to five at birth (Reduced Litter), which also restricted postnatal growth.
      Remaining litters from sham mothers were unaltered (Control). Offspring were
      studied at 6 mo of age. In males, both Restricted and Reduced Litter offspring
      had reduced gastrocnemius PPARgamma coactivator-1alpha (PGC-1alpha) mRNA and
      protein, and mitochondrial transcription factor A (mtTFA) and cytochrome oxidase
      (COX) III mRNA (P < 0.05), whereas only Restricted had reduced skeletal muscle
      COX IV mRNA and protein and glycogen (P < 0.05), despite unaltered glucose
      tolerance, homeostasis model assessment (HOMA) and intramuscular triglycerides.
      In females, only gastrocnemius mtTFA mRNA was lower in Reduced Litter offspring
      (P < 0.05). Furthermore, glucose tolerance was not altered in any female
      offspring, although HOMA and intramuscular triglycerides increased in Restricted
      offspring (P < 0.05). It is concluded that restriction of growth due to
      uteroplacental insufficiency alters skeletal muscle mitochondrial biogenesis and
      metabolic characteristics, such as glycogen and lipid levels, in a sex-specific
      manner in the adult rat in the absence of impaired glucose tolerance.
      Furthermore, an adverse postnatal environment induced by reducing litter size
      also restricts growth and alters skeletal muscle mitochondrial biogenesis and
      metabolic characteristics in the adult rat.

PMID- 18319354
TI  - Thrombospondin-1-induced migration is functionally dependent upon focal adhesion
      kinase.
AB  - Vascular smooth muscle cell migration is important in vascular disease.
      Previously, we showed thrombospondin-1 activates focal adhesion kinase in these
      cells. We hypothesized that focal adhesion kinase is important for thrombspondin
      1-induced vascular smooth muscle cell migration. Bovine aortic smooth muscle
      cells were transfected with FAK397, FAK-wild type, pcDNA, or beta-Gal plasmids.
      Migration was assessed with thrombospondin-1 or serum-free medium in quiescent
      transfected cells or quiescent cells pretreated with the focal adhesion kinase
      inhibitor, geldanamycin. Number of cells migrated per 5 fields (x400) were
      recorded. Antihemagglutinin immunoprecipitation and Western blot were used to
      examine thrombospondin-1-induced focal adhesion kinase phosphorylation in
      transfected cells. FAK397 transfection inhibited thrombospondin-1-induced focal
      adhesion kinase phosphorylation and migration (P < .05). Geldanamycin inhibited
      thrombospondin-1-induced smooth muscle cell migration (P < .05). In conclusion,
      vascular smooth muscle cells transfected with FAK397 inhibited thrombosponin-1
      induced migration and tyrosine phosphorylation. Further, geldanamycin also
      inhibited migration. These results suggest focal adhesion kinase is involved in
      thrombospondin-1-induced vascular smooth muscle cell migration.

PMID- 18319355
TI  - Local versus systemic mechanisms underlying supervised exercise training for
      intermittent claudication.
AB  - The mechanisms by which exercise training improves intermittent claudication
      remain unclear. In this article, the effects of local and systemic physiological
      factors on improved exercise tolerance after a supervised exercise program in
      claudicants are investigated. A total of 60 patients were randomized to 3 months
      of supervised exercise followed by 3 months of unsupervised exercise, or to
      exercise advice alone (control). Supervised exercise increased both pain-free and
      maximal walking distances. Heart rate during submaximal exercise and resting mean
      arterial pressure were lower after supervised exercise at 6 months. Serum lactate
      at maximum claudication increased significantly after 3 months in the supervised
      exercise group but this change had resolved by 6 months. Symptomatic improvement
      was accompanied by modest reductions in mean arterial pressure and submaximal
      heart rate on exercise. Increased serum lactate at maximum claudication
      subsequently declined despite continued improvement in walking distance,
      suggesting local adaptations to improve efficiency of muscle oxygen delivery
      and/or utilization.

PMID- 18319356
TI  - Atrial natriuretic peptide protects against ischemia-reperfusion injury in rabbit
      hearts in vivo.
AB  - The aim of this study is to investigate whether atrial natriuretic peptide can
      mimic preconditioning to protect ischemia or reperfusion injury in rabbit hearts.
      New Zealand white rabbits were randomized into 3 groups: (1) Controls. Hearts
      received a 60 minute-occlusion of the left anterior descending artery, followed
      by a 180 minute-reperfusion. (2) Preconditioning. Two 5-minute periods of
      ischemia separated by a 10-minute reperfusion, followed by a 60-minute ischemia
      and a 180-minute reperfusion. (3) Atrial natriuretic peptide treatment. Bolus
      injection of exogenous atrial natriuretic peptide (2.5 microg/kg) given
      intravenously at 15 minutes prior to 60 minute-ischemia followed by a 180-minute
      reperfusion. Myocardial necrotic area and area at risk of necrosis were
      determined by triphenyltetrazolium chloride staining. Ratio of necrotic area to
      area at risk was 49.95% +/- 1.15%, 7.95% +/- 0.33%, and 8.36% +/- 0.61% in the
      controls, preconditioning group, and atrial natriuretic peptide group,
      respectively. Both preconditioning and atrial natriuretic peptide significantly
      reduced the size of infarct caused by ischemia (preconditioning vs controls, P <
      .05; atrial natriuretic peptide vs controls, P < .05). Atrial natriuretic peptide
      can mimic ischemic preconditioning to protect rabbit hearts from prolonged
      ischemia and reperfusion injury. It may be involved in the cardioprotective
      mechanisms of preconditioning.

PMID- 18319357
TI  - Rituximab therapy in early recurrent focal segmental sclerosis after renal
      transplantation.

PMID- 18319358
TI  - The uraemic retention solute para-hydroxy-hippuric acid attenuates apoptosis of
      polymorphonuclear leukocytes from healthy subjects but not from haemodialysis
      patients.
AB  - BACKGROUND: Disturbed polymorphonuclear leukocyte (PMNL) apoptosis contributes to
      the dysregulation of the non-specific immune system in uraemia. Intracellular
      Ca(2+) modulates PMNL apoptotic cell death. We investigated the effect of para
      hydroxy-hippuric acid (PHA), an erythrocyte plasma membrane Ca(2+)-ATPase
      inhibitor accumulating in uraemic sera, and of cyclopiazonic acid (CPA), an
      inhibitor of the sarko/endoplasmatic Ca(2+)-ATPase, on PMNL apoptosis. METHODS:
      Apoptosis of PMNLs from healthy subjects and from haemodialysis (HD) patients was
      assessed after incubation for 20 h by evaluating morphological features under the
      fluorescence microscope and by measuring the DNA content and caspase activities
      by flow cytometry. The intracellular calcium concentration ([Ca(2+)](i)) was
      determined by measurement of fura-2 fluorescence using the 340/ 380 nm dual
      wavelength excitation. RESULTS: Spontaneous apoptosis of PMNLs from healthy
      subjects and from HD patients did not differ. PHA significantly attenuated, while
      CPA increased, the apoptotic cell death of PMNLs from healthy subjects. The PHA
      effect was not observed with PMNLs from HD patients, irrespective of whether the
      blood was drawn before or after HD treatment. Baseline [Ca(2+)](i) was increased
      in PMNLs obtained from HD patients before dialysis but reversed after dialysis.
      The PHA effects were not mediated via [Ca(2+)](i). The chemotactic peptide N
      formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induced a [Ca(2+)](i) increase
      and reduced PMNL survival. Extracellular Ca(2+) did not affect CPA- and fMLP
      induced apoptosis. CONCLUSIONS: PHA, without affecting [Ca(2+)](i), attenuates
      apoptosis of healthy but not of uraemic PMNLs. CPA and fMLP enhance PMNL
      apoptosis independently of Ca(2+) influx.

PMID- 18319359
TI  - Possible differential induction of phase 2 enzyme and antioxidant pathways by
      american ginseng, Panax quinquefolius.
AB  - Human immunodeficiency virus (HIV)-infected patients often take herbal medicines,
      which may interact with antiretrovirals. American ginseng induces phase 2 and
      antioxidant enzymes in vitro and might increase the clearance of zidovudine
      and/or enhance antioxidant activity. Ten healthy volunteers received 300 mg of
      zidovudine orally before and after 2 weeks of treatment with a ginsenoside
      enriched American ginseng extract 200 mg twice daily. This ginseng extract
      induced the phase 2 enzyme quinone reductase with an average concentration of
      doubling of enzyme activity of 190 microg/mL. Total ginsenoside content was 8.5
      +/- 0.5%. Pharmacokinetic profiles of zidovudine and oxidative stress marker
      concentrations were measured post-zidovudine dose. American ginseng does not
      significantly affect the formation clearance of zidovudine to its glucuronide
      (ratio post- to pre-American ginseng = 1.17; 90% confidence interval: 0.95-1.45;
      P = .21), total clearance (ratio = 0.97; 0.82-1.14; P = .70), or plasma
      zidovudine AUC0-8 (ratio = 1.03; 0.87-1.21; P = .77). Oxidative stress biomarkers
      are reduced post-American ginseng (F2-isoprostane ratio = 0.79; 0.72-0.86; P <
      .001; 8-hydroxy-deoxyguanosine ratio = 0.74; 0.59-0.92; P = .02). Two weeks of
      American ginseng does not alter zidovudine pharmacokinetics but reduces oxidative
      stress markers.

PMID- 18319360
TI  - Disposition and antimuscarinic effects of the urinary bladder spasmolytics
      propiverine: influence of dosage forms and circadian-time rhythms.
AB  - Propiverine extended release is expected to be better tolerated compared to
      immediate release tablets because of slower drug release and reduced formation of
      active metabolites in the colon. CYP3A4 and ABCC2, the major variables in
      pharmacokinetics of propiverine, are less expressed in the colon. Therefore,
      disposition and pharmacodynamics of propiverine were measured in a double-blind,
      double-dummy, crossover study with administration of 15 mg immediate release 3
      times daily for 7 days compared to 45 mg extended release once daily for 7 days
      in 24 healthy subjects. Twelve subjects also received 15 mg propiverine
      intravenously. Serum and urine propiverine levels were measured repeatedly
      following oral administration on day 7 for up to 72 hours and correlated to
      duodenal expression of CYP3A4, ABCB1, and ABCC2. Propiverine immediate release 3
      times daily was not different to extended release once daily in areas under the
      serum concentration-time curve (0-24 hours) and peak-trough fluctuation. The
      areas under the serum concentration-time curve of propiverine immediate release
      was circadian-time-dependent, with the lowest values during the night.
      Disposition of intravenous propiverine and propiverine immediate release
      administered in the night was influenced by intestinal expression of ABCC2. We
      concluded that oral absorption of propiverine is site-dependent and influenced by
      dosage form and circadian-time-dependent elimination processes.

PMID- 18319361
TI  - A 12-month, randomized, controlled study to evaluate exposure and cardiovascular
      risk factors in adult smokers switching from conventional cigarettes to a second
      generation electrically heated cigarette smoking system.
AB  - This randomized, controlled, forced-switching, open-label, parallel-group study
      in 97 adult male and female smokers of conventional cigarettes evaluated
      biomarkers of tobacco smoke exposure and cardiovascular risk factors. After
      baseline measurements, smokers were either switched to a second-generation
      electrically heated cigarette smoking system (EHCSS) or continued smoking
      conventional cigarettes for 12 months. Biomarkers of exposure and cardiovascular
      risk factors were measured at 0.5, 1, 2, 3, 4, 5, 6, 9, and 12 months. There was
      a rapid and sustained reduction in all biomarkers of exposure after switching to
      the EHCSS, with statistically significant reductions from baseline in nicotine
      equivalents (-18%), plasma cotinine (-16%), total 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (-73%), total 1-hydroxypyrene (-53%), urine mutagenicity (
      52%), 4-aminobiphenyl hemoglobin adducts (-43%), carboxyhemoglobin AUC7-23 h (
      80%), and 3-hydroxypropylmercapturic acid (-35%). These reductions in exposure in
      the EHCSS group were associated with statistically significant and
      pathophysiologically favorable changes in several cardiovascular risk factors,
      including white blood cell count (-0.78 x 10(3)/microL), hemoglobin (-0.16 g/dL),
      hematocrit (-0.44%), urine 11-dehydrothromboxane B2 (-374 ng/24 h), and high
      density lipoprotein cholesterol (+5 mg/dL).

PMID- 18319362
TI  - Lunchtime practices and problem behaviors among multiethnic urban youth.
AB  - Research has begun to show associations between adolescents' mealtime practices
      and their engagement in problem behaviors. Few studies have addressed this
      longitudinally and/or examined lunchtime practices during the school day. This
      study tests for associations between urban multiethnic middle school students' (N
      = 1498) lunchtime practices in the sixth grade and their engagement in problem
      behaviors by eighth grade. Positive associations were found between not eating
      lunch at school in the sixth grade and increased drug use and delinquency by
      eighth grade. Eating lunch outside of school was found to be significantly
      associated with smoking and marijuana use only. Gender differences in
      associations between lunchtime practices and problem behaviors were suggested.
      Implications for school policy and prevention efforts are discussed.

PMID- 18319363
TI  - Factors related to willingness to help survivors of intimate partner violence.
AB  - Although researchers have found that survivors of intimate partner violence seek
      support from a multitude of sources, ranging from professionals to informal
      support networks, little is known about the extent to which community members
      reach out to help survivors. This study explored the type of support provided to
      survivors and various factors that relate to individuals' willingness to help.
      Survivors were more likely to be helped by women, younger individuals, those who
      strongly endorsed criminal justice interventions for perpetrators, and those who
      perceived intimate partner violence as a frequently occurring issue in their
      communities. Two additional factors were found to relate to an individual's
      likelihood of assisting others, including witnessing intimate partner violence as
      a child and prior victimization. Further research is needed in this area to
      explore helper, survivor, and contextual characteristics that may affect one's
      likelihood to offer assistance to survivors.

PMID- 18319364
TI  - Won't you be my neighbor? Using an ecological approach to examine the impact of
      community on revictimization.
AB  - An ecological model is used to explore the moderating effects of community-level
      variables on the relation between childhood sexual, physical, and emotional abuse
      and adult intimate partner violence (IPV) within a sample of 98 African American
      women from low incomes. Results from hierarchical, binary logistics regressions
      analyses show that community-level variables (perceived neighborhood disorder and
      community cohesion) moderated the relation between childhood emotional abuse and
      adult physical IPV. Findings support the use of an ecological approach in
      examining the phenomena of revictimization. Clinical implications from a
      community and ecological perspective are discussed.

PMID- 18319365
TI  - Youth gang membership and serious violent victimization: the importance of
      lifestyles and routine activities.
AB  - Youth gangs have received substantial scholarly and public attention during the
      past two decades. Although most of the extant research on youth gang members has
      focused on their offending behaviors, recent studies have examined the
      victimization of youth gang members relative to their nongang peers. Gang members
      generally have been found to be at increased risk of victimization, although the
      reasons for this relationship have not fully been explored. The current study
      uses data from a multisite study of youth to explore whether the gang membership
      victimization link is mediated by lifestyles and routine activities. In other
      words, is gang members' involvement in delinquent lifestyles and routine
      activities a viable explanation for their increased risk of serious violent
      victimization? Implications of these findings and suggestions for future research
      and policy are discussed.

PMID- 18319366
TI  - Measuring sex differences in violence victimization and perpetration within date
      and same-sex peer relationships.
AB  - This study examines sex differences in the patterns of repeated perpetration and
      victimization of physical violence and psychological aggression within dating
      relationships and same-sex peer relationships. Data were obtained from the Youth
      Violence Survey: Linkages among Different Forms of Violence, conducted in 2004,
      and administered to all public school students enrolled in grades 7, 9, 11 and 12
      (N = 4,131) in a high-risk school district. Analyses of adolescents who dated in
      the past year (n = 2,888) show that girls are significantly more likely than boys
      to report physical violence and psychological aggression perpetration within
      dating relationships. However, boys are significantly more likely than girls to
      report physically injuring a date. Boys are also significantly more likely than
      girls to report physical violence victimization and perpetration within same-sex
      peer relationships. Implications and directions for future research are
      discussed.

PMID- 18319367
TI  - Women, anger, and aggression: an interpretative phenomenological analysis.
AB  - This study reports a qualitative phenomenological investigation of anger and
      anger-related aggression in the context of the lives of individual women.
      Semistructured interviews with five women are analyzed using interpretative
      phenomenological analysis. This inductive approach aims to capture the richness
      and complexity of the lived experience of emotional life. In particular, it draws
      attention to the context-dependent and relational dimension of angry feelings and
      aggressive behavior. Three analytic themes are presented here: the subjective
      experience of anger, which includes the perceptual confusion and bodily change
      felt by the women when angry, crying, and the presence of multiple emotions; the
      forms and contexts of aggression, paying particular attention to the range of
      aggressive strategies used; and anger as moral judgment, in particular
      perceptions of injustice and unfairness. The authors conclude by examining the
      analytic observations in light of phenomenological thinking.

PMID- 18319368
TI  - Domestically and generally violent forensic psychiatric outpatients: personality
      traits and behavior.
AB  - A group of 63 domestically violent patients and a group of 103 generally violent
      patients at a Dutch forensic psychiatric outpatient clinic are examined with
      regard to personality traits and problem behaviors to develop treatment programs
      for domestically violent patients. The domestically violent patients are more
      unstable from a psychological viewpoint but not more inclined to anger than the
      average Dutch male. They report less anxiety in situations in which criticism can
      be given but more anxiety in situations in which someone can be given a
      compliment. When comparing domestically violent patients with generally violent
      patients, domestically violent patients score lower on anger as disposition and
      on aggressive behavior than the generally violent patients do. However, both
      groups do not differ from each other in their score on the dimension of
      psychopathy.

PMID- 18319369
TI  - A preliminary investigation of the effects of giving testimony and learning yogic
      breathing techniques on battered women's feelings of depression.
AB  - Researchers have shown that mood and sense of control over one's life are
      significantly affected by testimony and other forms of disclosure and that
      learning to control breathing has positive effects on mood and anxiety. This
      preliminary experiment tests whether African American and European American
      abused women who give testimony about their experiences of intimate partner
      violence and learn how to use yogic breathing techniques have reduced feelings of
      depression. Results indicate that learning yogic breathing techniques alone and
      combined with giving testimony significantly reduces feelings of depression.
      Recasting women as authorities on domestic violence and teaching them how to calm
      their minds by focusing on yogic breathing may be simple and effective ways to
      help women take control over their bodies and lives.

PMID- 18319370
TI  - "The red zone": temporal risk for unwanted sex among college students.
AB  - The "red zone" usually refers to the first few weeks of the first semester at
      college, when female students are believed to be at greatest risk for
      experiencing unwanted sex. We tested this notion using data from a survey study
      of 207 first-and second-year students (121 women, 84 men) at a small, liberal
      arts university. Results demonstrated only one significant elevation in incidence
      rates of first- and second-year women's unwanted sexual experiences (sexual
      touching, attempted and completed anal, oral, and vaginal sex), between the end
      of the first month and fall break (mid-October) during the second year at school.
      Previous research and local information about the relevant behaviors of sorority
      and fraternity members is discussed in light of these findings to provide
      heuristic material for further empirical testing. Because risk may involve both
      temporal and situational factors, systematic collection and dissemination of
      local data are recommended.

PMID- 18319371
TI  - Premilitary adult sexual assault victimization and perpetration in a Navy recruit
      sample.
AB  - Female (n = 5,226) and male (n = 5,969) U.S. Navy recruits completed a survey
      assessing their premilitary histories of adult sexual assault (SA), defined as
      attempted or completed rape since the age of 14. The survey was completed under
      anonymous or identified conditions. Overall, 39% of women reported premilitary SA
      victimization and 13% of men admitted premilitary SA perpetration. As predicted,
      rates were significantly higher in the anonymous than in the identified
      condition. For the sample of women as a whole, marital status, ethnicity, and
      family income were associated with SA victimization; for men, only marital status
      was associated with SA perpetration. Compared to previous college samples, Navy
      recruits were more likely to have previous SA experience. Given the negative
      consequences associated with SA victimization and perpetration, the present study
      reinforces the desirability of developing additional treatment, education, and
      prevention programs to reduce the occurrence of SA among military recruits.

PMID- 18319372
TI  - Cumulative experiences of violence among high-risk urban youth.
AB  - This study examines type-specific and cumulative experiences of violence among a
      vulnerable population of youth. Sixty high-risk, shelter-dwelling, urban youth
      were interviewed regarding their history of childhood maltreatment, exposure to
      community violence (ECV), and experience with intimate partner violence (IPV).
      Results show a high prevalence and high degree of overlap among multiple types of
      violence exposure. Childhood physical, sexual (CSA), and emotional (CEA) abuse
      were interrelated and were associated with ECV. Cumulative experiences of
      childhood abuse (CCA) had a graded association with IPV victimization. In
      multivariate analyses, CCA and ECV were independently associated with IPV
      victimization. Gender moderated the effect of one association: CEA raised the
      risk of IPV victimization for girls but not for boys. Only CSA predicted IPV
      perpetration. Findings suggest that cumulative exposures to violence create
      cumulative risk for experiencing more violence. Shelter-dwelling, urban youth may
      be particularly vulnerable to this additive effect.

PMID- 18319373
TI  - Collaborating for family safety: results from the Greenbook multisite evaluation.

PMID- 18319374
TI  - Neighborhood disorganization, substance use, and violence among adolescents in
      Puerto Rico.
AB  - This study investigates the role of neighborhoods in adolescent violence in poor
      neighborhoods in San Juan, Puerto Rico. The study is part of a larger
      longitudinal project examining risk and resilience in adolescents' ages 12 to 15
      years old and their caregivers. Using a cross-sectional design, a self-completion
      questionnaire, and an interviewer questionnaire, the authors assessed violent
      behaviors among participants across demographics, characteristics, and
      neighborhood social disorganization using the concepts of physical disorders and
      social disorder. Adolescent violence was positively associated with social
      disorder. The finding that adults in these neighborhoods walk around with visible
      firearms and engage in fighting, may have led adolescents to perceive that
      violence is an accepted behavior. Furthermore, socially disorganized
      neighborhoods might be less likely to organize on their own behalf because the
      occurrence of negative experience limits the amount of social support and
      resources that are available in the neighborhood.

PMID- 18319375
TI  - Prostitute homicides: a descriptive study.
AB  - It has been estimated that women involved in street prostitution are 60 to 100
      times more likely to be murdered than are nonprostitute females. In addition,
      homicides of prostitutes are notoriously difficult to investigate and, as such,
      many cases remain unsolved. Despite this large risk factor, little literature
      exists on homicides of prostitutes, and there is a lack of basic statistics and
      knowledge regarding this very specific victim group that could possibly help
      investigators. The aim of the current study is to conduct an exploratory study to
      explore the key characteristics of this group and how they differ from other
      subgroups of homicide. Forty-six cases of U.K. prostitute homicides are analyzed
      and compared to 59 male offender-female victim nonsexual homicide cases and 17
      male offender-female victim sexual homicide cases.

PMID- 18319376
TI  - Comorbidity of psychiatric disorders and parental psychiatric disorders in a
      sample of Iranian children with ADHD.
AB  - OBJECTIVE: To study the psychiatric comorbidity of a clinical sample of children
      with ADHD and the psychiatric disorders in their parents. METHOD: Structured
      psychiatric interviews assessing lifetime psychiatric disorders by DSM-IV
      criteria, using the Farsi version of the Schedule for Affective Disorders and
      Schizophrenia. RESULTS: The mean age of the children was 8.7, mothers, 40.1, and
      fathers, 34.6 years. Only 7.6% of the boys and 21.7% of the girls manifested ADHD
      without any other psychiatric comorbidity. The most common comorbid disorders
      were disruptive behavior disorders and anxiety disorders. The prevalence of
      lifetime ADHD in the parents was 45.8% and 17.7%, respectively. The rate for
      major depressive disorder in mothers and fathers was 48.1% and 43.0%,
      respectively. DISCUSSION: The clinical sample of ADHD children typically had at
      least one other psychiatric disorder, usually oppositional defiant disorder in
      boys and anxiety disorders in girls. The most common psychiatric disorder in the
      parents was mood disorder.

PMID- 18319377
TI  - Translation of health programs for American Indians in the United States.
AB  - American Indian and Alaska Native (AI/AN) cultures in the United States include a
      diverse group of indigenous cultures that have been affected by their contact
      with European Americans and have suffered adverse psychological, physical, and
      economic consequences. AI/AN adolescents have the highest prevalence of cigarette
      smoking of all U.S. ethnic groups. Culturally competent health promotion programs
      are needed to enhance their resiliency and help them avoid recreational,
      addictive use of commercial tobacco. The authors describe the diverse AI/AN
      populations and their unique health and social issues, including adolescent
      smoking. They present examples of smoking prevention programs tailored or adapted
      for AI/AN adolescents and make recommendations for implementation and evaluation
      of prototype programs. Recommendations include involving the community,
      respecting tribes' wishes for confidentiality, being aware of IRB issues,
      beginning with formative and qualitative research, using culturally appropriate
      measures, understanding the diversity of AI/AN cultures, and involving multiple
      generations of the family.

PMID- 18319378
TI  - Busy perceivers and ineffective suppression goals: a critical role for distracter
      thoughts.
AB  - With limited cognitive resources, suppressing thoughts can be ineffective. The
      detrimental effects of cognitive load on suppression have typically been
      attributed to increased accessibility of avoided thoughts. However, little
      research has examined distracter thoughts and their contribution to these
      effects. In three studies, participants pursued suppression goals related to
      social judgments (e.g., avoid negative thoughts about a target's performance)
      with sufficient or diminished cognitive resources. Compared to suppressors not
      under cognitive load, suppressors under load drew more negative social inferences
      when pursuing a negative suppression goal and more positive inferences under a
      positive suppression goal; load did not similarly disrupt a concentration goal
      (i.e., focus on positive thoughts). Across studies, load reduced high-quality
      oppositely valenced distracter thoughts, and these distracter thoughts mediated
      the detrimental effects of load on social inferences. The discussion focuses on
      mechanisms underlying the effects of load on suppression, implications, and
      future directions for research on ironic processes.

PMID- 18319379
TI  - Acridinediones: selective and potent inhibitors of the malaria parasite
      mitochondrial bc1 complex.
AB  - The development of drug resistance to affordable drugs has contributed to a
      global increase in the number of deaths from malaria. This unacceptable situation
      has stimulated research for new drugs active against multidrug-resistant
      Plasmodium falciparum parasites. In this regard, we show here that deshydroxy-1
      imino derivatives of acridine (i.e., dihydroacridinediones) are selective
      antimalarial drugs acting as potent (nanomolar K(i)) inhibitors of parasite
      mitochondrial bc(1) complex. Inhibition of the bc(1) complex led to a collapse of
      the mitochondrial membrane potential, resulting in cell death (IC(50)
      approximately 15 nM). The selectivity of one of the dihydroacridinediones against
      the parasite enzyme was some 5000-fold higher than for the human bc(1) complex,
      significantly higher ( approximately 200 fold) than that observed with
      atovaquone, a licensed bc(1)-specific antimalarial drug. Experiments performed
      with yeast manifesting mutations in the bc(1) complex reveal that binding is
      directed to the quinol oxidation site (Q(o)) of the bc(1) complex. This is
      supported by favorable binding energies for in silico docking of
      dihydroacridinediones to P. falciparum bc(1) Q(o). Dihydroacridinediones
      represent an entirely new class of bc(1) inhibitors and the potential of these
      compounds as novel antimalarial drugs is discussed.

PMID- 18319380
TI  - The tuberculin skin test: a hundred, not out?

PMID- 18319381
TI  - One size does not fit all: getting drug doses right for children.

PMID- 18319382
TI  - "We want everything done".

PMID- 18319383
TI  - Normal x rays in Perthes disease.

PMID- 18319384
TI  - The midline nasal lesion.

PMID- 18319385
TI  - Results of lung transplantation for cystic fibrosis in the USA, 1992-2002.

PMID- 18319386
TI  - Childhood body-mass index and adult coronary risk.

PMID- 18319387
TI  - Pallidal stimulation for pantothenate kinase-associated neurodegeneration
      dystonia.
AB  - Pantothenate kinase-associated neurodegeneration is associated with generalised
      dystonia and cognitive deterioration. Limited evidence suggests that pallidal
      deep brain stimulation improves physical functioning. This is a report of the
      assessment and treatment of a severely affected patient in whom pallidal deep
      brain stimulation improved both physical and psychosocial functioning.
      Implications for treatment are briefly discussed.

PMID- 18319388
TI  - "Glue lung": pulmonary micro-embolism caused by the glue used during
      interventional radiology.

PMID- 18319389
TI  - Monitoring of newborn weight, breast feeding and severe neurological sequelae
      secondary to dehydration.

PMID- 18319390
TI  - In neonates requiring intravascular volume resuscitation in the use of gelofusine
      safe and efficacious?

PMID- 18319393
TI  - Pharmacist monitoring of QTc interval-prolonging medications in critically ill
      medical patients: a pilot study.
AB  - BACKGROUND: No data exist regarding the value of pharmacist monitoring of drugs
      associated with QTc interval prolongation. OBJECTIVE: To assess the capability,
      clinical impact, and economic impact of pharmacists monitoring for drug-induced
      QTc interval prolongation in critically ill medical adult patients. METHODS: In a
      prospective, parallel-group study, 149 consecutive medical intensive care unit
      (ICU) patients prescribed a QTc interval-prolonging drug at the Los Angeles
      County + University of Southern California Medical Center were assigned on
      alternating days to an intervention group (clinical pharmacist on physician team
      monitored drugs using a standardized algorithm) or a standard care group (team
      without pharmacist using an algorithm). The monitoring algorithm used daily
      assessments of electrocardiograms and laboratory data to generate
      pharmacotherapeutic recommendations. The primary endpoint was the frequency of
      QTc interval prolongation (>500 msec at any time or an increase > or =60 msec
      over baseline). Secondary endpoints included QTc interval greater than 470 msec
      in women or greater than 450 msec in men, mean increase in QTc interval at 48
      hours, recommendation acceptance rate, and cost of care. RESULTS: QTc interval
      prolongation occurred less frequently in the intervention group compared with the
      standard care group (19% vs 39%, respectively; p = 0.006). Incidence of QTc
      interval greater than 500 msec (13% vs 33%, respectively; p = 0.003) was also
      lower in the intervention group. Incidence of QTc interval increase of 60 msec or
      more over baseline (12% vs 21%, respectively; p = 0.12) and increase in QTc
      interval at 48 hours over baseline (mean +/- SD; 6.4 +/- 40.8 vs 18.2 +/- 42.3
      msec, respectively; p = 0.097) were not significantly different between the
      groups. Algorithm-generated recommendations were accepted 70% of the time by the
      intervention group physician team. Total cost and cost per day were not
      significantly different between groups. CONCLUSIONS: In this preliminary study,
      pharmacist monitoring of QTc interval-prolonging drugs using a simple algorithm
      was feasible and reduced the risk of QTc interval prolongation. Further studies
      that monitor other proarrhythmic medications are warranted.

PMID- 18319394
TI  - Indications for dual antiplatelet therapy with aspirin and clopidogrel: evidence
      based recommendations for use.
AB  - OBJECTIVE: To review the literature assessing dual antiplatelet therapy with
      aspirin and clopidogrel and subsequently provide evidence-based recommendations
      for appropriate indications and length of therapy. DATA SOURCES: An English
      language MEDLINE search (1950-December 2007) was conducted using the search terms
      antiplatelet, aspirin, thienopyridine, and clopidogrel to identify articles
      assessing dual antiplatelet therapy. Evaluation of references from identified
      trials for possible inclusion was also conducted. STUDY SELECTION AND DATA
      EXTRACTION: All studies that assessed treatment with the combination of aspirin
      and clopidogrel for any indication were included. DATA SYNTHESIS: Aspirin and
      clopidogrel have complementary mechanisms of action to inhibit platelet function.
      Indications that have been studied include coronary artery disease (CAD),
      atherosclerotic ischemic stroke, and atrial fibrillation. This combination has
      been beneficial in patients with acute coronary syndrome (ACS) with or without
      percutaneous coronary intervention (PCI), and in PCI patients without an acute
      event. There is a small but significant risk for increased bleeding with dual
      antiplatelet therapy for these indications. When used in patients with a history
      of atherosclerotic ischemic stroke or for prevention of cardioembolic stroke in
      patients with atrial fibrillation, this combination has been shown to increase
      bleeding, providing no clinical benefit, and to increase outcomes including
      stroke, myocardial infarction, and death, respectively. CONCLUSIONS: There is
      evidence to support use of aspirin in combination with clopidogrel for patients
      presenting with all ACS types, as well as for patients presenting with PCI for
      any indication. The treatment duration varies, but patients who have received
      stenting should receive at least 1 year of combination therapy. There is no
      evidence to support this combination for primary prevention of CAD or
      atherosclerotic ischemic events, secondary prevention of stable CAD, or
      prevention of cardioembolic stroke in patients with atrial fibrillation. The
      possible benefits of dual antiplatelet therapy also must be weighed against the
      risk of bleeding.

PMID- 18319396
TI  - Promoter-proximal introns in Arabidopsis thaliana are enriched in dispersed
      signals that elevate gene expression.
AB  - Introns that elevate mRNA accumulation have been found in a wide range of
      eukaryotes. However, not all introns affect gene expression, and direct testing
      is currently the only way to identify stimulatory introns. Our genome-wide
      analysis in Arabidopsis thaliana revealed that promoter-proximal introns as a
      group are compositionally distinct from distal introns and that the degree to
      which an individual intron matches the promoter-proximal intron profile is a
      strong predictor of its ability to increase expression. We found that the
      sequences responsible for elevating expression are dispersed throughout an
      enhancing intron, as is a candidate motif that is overrepresented in first
      introns and whose occurrence in tested introns is proportional to its effect on
      expression. The signals responsible for intron-mediated enhancement are
      apparently conserved between Arabidopsis and rice (Oryza sativa) despite the
      large evolutionary distance separating these plants.

PMID- 18319397
TI  - The Arabidopsis thaliana type I Isopentenyl Diphosphate Isomerases are targeted
      to multiple subcellular compartments and have overlapping functions in isoprenoid
      biosynthesis.
AB  - To form the building blocks of isoprenoids, isopentenyl diphosphate (IPP)
      isomerase activity, which converts IPP to dimethylallyl diphosphate (DMAPP),
      appears to be necessary in cytosol, plastids, and mitochondria. Arabidopsis
      thaliana contains only two IPP isomerases (Isopentenyl Diphosphate Isomerase1
      [IDI1] and IDI2). Both encode proteins with N-terminal extensions similar to
      transit peptides and are expressed in all organs, with IDI1 less abundant than
      IDI2. Examination of enhanced green fluorescent protein fusions established that
      IDI1 is mainly in the plastid, whereas IDI2 is mainly in the mitochondria. Both
      proteins are also in the cytosol as a result of their translation from naturally
      occurring shorter transcripts lacking transit peptides, as demonstrated by 5'
      rapid amplification of cDNA ends cloning. IPP isomerase activity in the cytosol
      was confirmed by uniform labeling of IPP- and DMAPP-derived units of the
      cytoplasmic isoprenoid product, sitosterol, when labeled mevalonate was
      administered. Analysis of mutant lines showed that double mutants were nonviable,
      while homozygous single mutants had no major morphological or chemical
      differences from the wild type except for flowers with fused sepals and
      underdeveloped petals on idi2 mutants. Thus, each of the two Arabidopsis IPP
      isomerases is found in multiple but partially overlapping subcellular locations,
      and each can compensate for the loss of the other through partial redundancy in
      the cytosol.

PMID- 18319398
TI  - Common variable immunodeficiency disorders: division into distinct clinical
      phenotypes.
AB  - The European Common Variable Immunodeficiency Disorders registry was started in
      1996 to define distinct clinical phenotypes and determine overlap within
      individual patients. A total of 7 centers contributed patient data, resulting in
      the largest cohort yet reported. Patients (334), validated for the diagnosis,
      were followed for an average of 25.6 years (9461 patient-years). Data were used
      to define 5 distinct clinical phenotypes: no complications, autoimmunity,
      polyclonal lymphocytic infiltration, enteropathy, and lymphoid malignancy. A
      total of 83% of patients had only one of these phenotypes. Analysis of mortality
      showed a considerable reduction in the last 15 years and that different
      phenotypes were associated with different survival times. Types of complications
      and clinical phenotypes varied significantly between countries, indicating the
      need for large, international registries. Ages at onset of symptoms and diagnosis
      were shown to have a Gaussian distribution, but were not useful predictors of
      phenotype. The only clinical predictor was polyclonal lymphocytic infiltration,
      which was associated with a 5-fold increased risk of lymphoid malignancy. There
      was widespread variation in the levels of serum immunoglobulin isotypes as well
      as in the percentages and absolute numbers of B cells, confirming the
      heterogeneity of these conditions. Higher serum IgM and lower circulating CD8
      proportions were found to be predictive markers for polyclonal lymphocytic
      infiltration and autoimmunity, respectively.

PMID- 18319400
TI  - A role for interleukin-12/23 in the maturation of human natural killer and CD56+
      T cells in vivo.
AB  - Natural killer (NK) cells have been originally defined by their "naturally
      occurring" effector function. However, only a fraction of human NK cells is
      reactive toward a panel of prototypical tumor cell targets in vitro, both for the
      production of interferon-gamma (IFN-gamma) and for their cytotoxic response. In
      patients with IL12RB1 mutations that lead to a complete IL-12Rbeta1 deficiency,
      the size of this naturally reactive NK cell subset is diminished, in particular
      for the IFN-gamma production. Similar data were obtained from a patient with a
      complete deficit in IL-12p40. In addition, the size of the subset of effector
      memory T cells expressing CD56 was severely decreased in IL-12Rbeta1- and IL
      12p40-deficient patients. Human NK cells thus require in vivo priming with IL
      12/23 to acquire their full spectrum of functional reactivity, while T cells are
      dependent upon IL-12/23 signals for the differentiation and/or the maintenance of
      CD56(+) effector memory T cells. The susceptibility of IL-12/23 axis-deficient
      patients to Mycobacterium and Salmonella infections in combination with the
      absence of mycobacteriosis or salmonellosis in the rare cases of human NK cell
      deficiencies point to a role for CD56(+) T cells in the control of these
      infections in humans.

PMID- 18319399
TI  - A critical role of Rap1b in B-cell trafficking and marginal zone B-cell
      development.
AB  - B-cell development is orchestrated by complex signaling networks. Rap1 is a
      member of the Ras superfamily of small GTP-binding proteins and has 2 isoforms,
      Rap1a and Rap1b. Although Rap1 has been suggested to have an important role in a
      variety of cellular processes, no direct evidence demonstrates a role for Rap1 in
      B-cell biology. In this study, we found that Rap1b was the dominant isoform of
      Rap1 in B cells. We discovered that Rap1b deficiency in mice barely affected
      early development of B cells but markedly reduced marginal zone (MZ) B cells in
      the spleen and mature B cells in peripheral and mucosal lymph nodes. Rap1b
      deficient B cells displayed normal survival and proliferation in vivo and in
      vitro. However, Rap1b-deficient B cells had impaired adhesion and reduced
      chemotaxis in vitro, and lessened homing to lymph nodes in vivo. Furthermore, we
      found that Rap1b deficiency had no marked effect on LPS-, BCR-, or SDF-1-induced
      activation of mitogen-activated protein kinases and AKT but clearly impaired SDF
      1-mediated activation of Pyk-2, a key regulator of SDF-1-mediated B-cell
      migration. Thus, we have discovered a critical and distinct role of Rap1b in
      mature B-cell trafficking and development of MZ B cells.

PMID- 18319401
TI  - A 21-year-old man with chronic pancreatitis.
AB  - Chronic pancreatitis is a disease for which the diagnosis may be difficult to
      ascertain and the treatments are limited. Using the case of a 21-year-old man who
      has had recurrent episodes of epigastric pain since age 10 years and was
      ultimately diagnosed as having idiopathic pancreatitis complicated by pancreatic
      duct stones, we discuss the evaluation and treatment of chronic pancreatitis.
      Diagnosis is based on thorough history taking, physical examination, and
      carefully selected imaging studies. Etiologies may be structural or
      nonstructural; genes predisposing to chronic pancreatitis have been identified.
      An evidence-based approach to treatment is limited by a paucity of randomized
      controlled trials. We address the patient's concerns regarding chronic
      pancreatitis, including what he should expect over the next several years,
      whether endoscopic or surgical therapies should be considered, and whether there
      are any cures.

PMID- 18319402
TI  - The cover. Still life with parrots.

PMID- 18319403
TI  - A piece of my mind. Lessons from the Santa Fe trail.

PMID- 18319404
TI  - Experts debate need to improve quality and oversight of continuing education.

PMID- 18319405
TI  - DHHS halts quality improvement study: policy may hamper tests of methods to
      improve care.

PMID- 18319406
TI  - Research reveals low immunization rates and vaccination awareness among adults.

PMID- 18319407
TI  - Cardiorespiratory fitness, adiposity, and mortality.

PMID- 18319408
TI  - Cardiorespiratory fitness, adiposity, and mortality.

PMID- 18319409
TI  - The future of general surgery.

PMID- 18319410
TI  - The future of general surgery.

PMID- 18319411
TI  - Commercial features of placebo and therapeutic efficacy.

PMID- 18319412
TI  - Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based
      chemoradiation following resection of pancreatic adenocarcinoma: a randomized
      controlled trial.
AB  - CONTEXT: Among patients with locally advanced metastatic pancreatic
      adenocarcinoma, gemcitabine has been shown to improve outcomes compared with
      fluorouracil. OBJECTIVE: To determine if the addition of gemcitabine to adjuvant
      fluorouracil chemoradiation (chemotherapy plus radiation) improves survival for
      patients with resected pancreatic adenocarcinoma. DESIGN, SETTING, AND
      PARTICIPANTS: Randomized controlled phase 3 trial of patients with complete gross
      total resection of pancreatic adenocarcinoma and no prior radiation or
      chemotherapy enrolled between July 1998 and July 2002 with follow-up through
      August 18, 2006, at 164 US and Canadian institutions. INTERVENTION: Chemotherapy
      with either fluorouracil (continuous infusion of 250 mg/m2 per day; n = 230) or
      gemcitabine (30-minute infusion of 1000 mg/m2 once per week; n = 221) for 3 weeks
      prior to chemoradiation therapy and for 12 weeks after chemoradiation therapy.
      Chemoradiation with a continuous infusion of fluorouracil (250 mg/m2 per day) was
      the same for all patients (50.4 Gy). MAIN OUTCOME MEASURES: Survival for all
      patients and survival for patients with pancreatic head tumors were the primary
      end points. Secondary end points included toxicity. RESULTS: A total of 451
      patients were randomized, eligible, and analyzable. Patients with pancreatic head
      tumors (n = 388) had a median survival of 20.5 months and a 3-year survival of
      31% in the gemcitabine group vs a median survival of 16.9 months and a 3-year
      survival of 22% in the fluorouracil group (hazard ratio, 0.82 [95% confidence
      interval, 0.65-1.03]; P = .09). The treatment effect was strengthened on
      multivariate analysis (hazard ratio, 0.80 [95% confidence interval, 0.63-1.00]; P
      = .05). Grade 4 hematologic toxicity was 1% in the fluorouracil group and 14% in
      the gemcitabine group (P < .001) without a difference in febrile neutropenia or
      infection. There were no differences in the ability to complete chemotherapy or
      radiation therapy (>85%). CONCLUSIONS: The addition of gemcitabine to adjuvant
      fluorouracil-based chemoradiation was associated with a survival benefit for
      patients with resected pancreatic cancer, although this improvement was not
      statistically significant. TRIAL REGISTRATION: clinicaltrials.gov Identifier:
      NCT00003216.

PMID- 18319413
TI  - Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in
      asymptomatic and symptomatic adults.
AB  - CONTEXT: Colorectal cancer is the second leading cause of cancer death in the
      United States. Prevention has focused on the detection and removal of polypoid
      neoplasms. Data are limited on the significance of nonpolypoid colorectal
      neoplasms (NP-CRNs). OBJECTIVES: To determine the prevalence of NP-CRNs in a
      veterans hospital population and to characterize their association with
      colorectal cancer. DESIGN, SETTING, AND PATIENTS: Cross-sectional study at a
      veterans hospital in California with 1819 patients undergoing elective
      colonoscopy from July 2003 to June 2004. MAIN OUTCOME MEASURES: Endoscopic
      appearance, location, size, histology, and depth of invasion of neoplasms.
      RESULTS: The overall prevalence of NP-CRNs was 9.35% (95% confidence interval
      [95% CI], 8.05%-10.78%; n = 170). The prevalence of NP-CRNs in the subpopulations
      for screening, surveillance, and symptoms was 5.84% (95% CI, 4.13%-8.00%; n =
      36), 15.44% (95% CI, 12.76%-18.44%; n = 101), and 6.01% (95% CI, 4.17%-8.34%; n =
      33), respectively. The overall prevalence of NP-CRNs with in situ or submucosal
      invasive carcinoma was 0.82% (95% CI, 0.46%-1.36%; n = 15); in the screening
      population, the prevalence was 0.32% (95% CI, 0.04%-1.17%; n = 2). Overall, NP
      CRNs were more likely to contain carcinoma (odds ratio, 9.78; 95% CI, 3.93-24.4)
      than polypoid lesions, irrespective of the size. The positive size-adjusted
      association of NP-CRNs with in situ or submucosal invasive carcinoma was also
      observed in subpopulations for screening (odds ratio, 2.01; 95% CI, 0.27-15.3)
      and surveillance (odds ratio, 63.7; 95% CI, 9.41-431). The depressed type had the
      highest risk (33%). Nonpolypoid colorectal neoplasms containing carcinoma were
      smaller in diameter as compared with the polypoid ones (mean [SD] diameter, 15.9
      [10.2] mm vs 19.2 [9.6] mm, respectively). The procedure times did not change
      appreciably as compared with historical controls. CONCLUSION: In this group of
      veteran patients, NP-CRNs were relatively common lesions diagnosed during routine
      colonoscopy and had a greater association with carcinoma compared with polypoid
      neoplasms, irrespective of size.

PMID- 18319414
TI  - Health risks and benefits 3 years after stopping randomized treatment with
      estrogen and progestin.
AB  - CONTEXT: The Women's Health Initiative (WHI) trial of estrogen plus progestin vs
      placebo was stopped early, after a mean 5.6 years of follow-up, because the
      overall health risks of hormone therapy exceeded its benefits. OBJECTIVE: To
      report health outcomes at 3 years (mean 2.4 years of follow-up) after the
      intervention was stopped. DESIGN, SETTING, AND PARTICIPANTS: The intervention
      phase was a double-blind, placebo-controlled, randomized trial of conjugated
      equine estrogens (CEE) 0.625 mg daily plus medroxyprogesterone acetate (MPA) 2.5
      mg daily, in 16,608 women aged 50 through 79 years, recruited by 40 centers from
      1993 to 1998. The postintervention phase commenced July 8, 2002, and included 15
      730 women. MAIN OUTCOME MEASURES: Semi-annual monitoring and outcomes
      ascertainment continued per trial protocol. The primary end points were coronary
      heart disease and invasive breast cancer. A global index summarizing the balance
      of risks and benefits included the 2 primary end points plus stroke, pulmonary
      embolism, endometrial cancer, colorectal cancer, hip fracture, and death due to
      other causes. RESULTS: The risk of cardiovascular events after the intervention
      was comparable by initial randomized assignments, 1.97% (annualized rate) in the
      CEE plus MPA (343 events) and 1.91% in the placebo group (323 events). A greater
      risk of malignancies occurred in the CEE plus MPA than in the placebo group
      (1.56% [n = 281] vs 1.26% [n = 218]; hazard ratio [HR], 1.24; 95% confidence
      interval [CI], 1.04-1.48). More breast cancers were diagnosed in women who had
      been randomly assigned to receive CEE plus MPA vs placebo (0.42% [n = 79] vs
      0.33% [n = 60]; HR, 1.27; 95% CI, 0.91-1.78) with a modest trend toward a lower
      HR during the follow-up after the intervention. All-cause mortality was somewhat
      higher in the CEE plus MPA than in the placebo group (1.20% [n = 233] vs 1.06% [n
      = 196]; HR, 1.15; 95% CI, 0.95-1.39). The global index of risks and benefits was
      unchanged from randomization through March 31, 2005 (HR, 1.12; 95% CI, 1.03
      1.21), indicating that the risks of CEE plus MPA exceed the benefits for chronic
      disease prevention. CONCLUSIONS: The increased cardiovascular risks in the women
      assigned to CEE plus MPA during the intervention period were not observed after
      the intervention. A greater risk of fatal and nonfatal malignancies occurred
      after the intervention in the CEE plus MPA group and the global risk index was
      12% higher in women randomly assigned to receive CEE plus MPA compared with
      placebo. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00000611.

PMID- 18319415
TI  - Update: a 62-year-old woman with a new diagnosis of breast cancer.

PMID- 18319416
TI  - Who really pays for health care? The myth of "shared responsibility".

PMID- 18319417
TI  - Financial support of continuing medical education.

PMID- 18319418
TI  - The loss of serendipity in psychopharmacology.

PMID- 18319419
TI  - Adjuvant therapy for surgically resected pancreatic adenocarcinoma.

PMID- 18319420
TI  - Nonpolypoid colorectal neoplasia in the United States: the parachute is open.

PMID- 18319421
TI  - JAMA patient page. Peripheral neuropathy.

PMID- 18319422
TI  - Using an empirical binomial hierarchical Bayesian model as an alternative to
      analyzing data from multisite studies.
AB  - This article explores the statistical methodologies used in demonstration and
      effectiveness studies when the treatments are applied across multiple settings.
      The importance of evaluating and how to evaluate these types of studies are
      discussed. As an alternative to standard methodology, the authors of this article
      offer an empirical binomial hierarchical Bayesian model as a way to effectively
      evaluate multisite studies. An application of using the Bayesian model in a real
      world multisite study is given.

PMID- 18319423
TI  - The truncation-by-death problem: what to do in an experimental evaluation when
      the outcome is not always defined.
AB  - Although experiments are viewed as the gold standard for evaluation, some of
      their benefits may be lost when, as is common, outcomes are not defined for some
      sample members. In evaluations of marriage interventions, for example, a key
      outcome--relationship quality--is undefined when a couple splits up. This article
      shows how treatment-control differences in mean outcomes can be misleading when
      outcomes are not defined for everyone and discusses ways to identify the
      seriousness of the problem. Potential solutions to the problem are described,
      including approaches that rely on simple treatment-control differences-in-means
      as well as more complex modeling approaches.

PMID- 18319424
TI  - Mixed results in a transitional planning program for alternative school students.
AB  - Disciplinary alternative schools have a reputation as gateways to the juvenile
      and criminal justice systems. The authors conducted an evaluation of an
      intervention (Strategies for Success) designed to divert seventh-, eighth-, and
      ninth-grade alternative school students from this gateway. They used propensity
      score matching and a multivariate random effects model to estimate program
      impacts and found that the program not only increased attendance rates, at least
      in the short term, but also increased the likelihood of reassignment to
      alternative schools. The discussion focuses on possible reasons and solutions for
      high rates of return to alternative school and for the erosion of program
      effects.

PMID- 18319425
TI  - Prion protein in sheep urine.
AB  - The misfolded form of cellular prion protein (PrP(C)) is the main component of
      the infectious agent of transmissible spongiform encephalopathies and the
      validated biomarker for these diseases. The expression of PrP(C) is highest in
      the central nervous system and has been found in peripheral tissues. Soluble
      PrP(C) has been detected in cerebrospinal fluid, urine, serum, milk, and seminal
      plasma. In this study, attempts were made to characterize prion protein in urine
      samples from normal and scrapie-infected sheep. Urine samples from scrapie
      infected sheep and age-matched healthy sheep were collected and analyzed by
      Western blot following concentration. A protease K-sensitive protein band with a
      molecular weight of approximately 27-30 kDa was visualized after immunoblotting
      with anti-PrP monoclonal antibodies to a C-terminal part of PrP(C), but not after
      immunoblotting with monoclonal antibodies to an N-terminal epitope of PrP(C) or
      with secondary antibodies only. The amount of PrP(C) in the urine of 49 animals
      (control group: n = 16; naturally scrapie-infected group: n = 33) was estimated
      by comparison with known amounts of ovine recombinant PrP in the immunoblot.
      Background concentration of PrP(C) in urine was found to be 0-0.16 ng/ml
      (adjusted to the initial nonconcentrated volume of the urine samples). Seven out
      of 33 naturally scrapie-infected animals had an elevated level (0.3-4.7 ng/ml) of
      PrP(C) in urine. The origin of PrP(C) in urine and the reason for the increased
      level of PrP(C) in scrapie-infected sheep urine has yet to be explored.

PMID- 18319426
TI  - Comparison of two real-time reverse transcription polymerase chain reaction
      assays for the detection of Equine arteritis virus nucleic acid in equine semen
      and tissue culture fluid.
AB  - Two previously developed TaqMan fluorogenic probe-based 1-tube real-time reverse
      transcription polymerase chain reaction (real-time RT-PCR) assays (T1 and T2)
      were compared and validated for the detection of Equine arteritis virus (EAV)
      nucleic acid in equine semen and tissue culture fluid (TCF). The specificity and
      sensitivity of these 2 molecular-based assays were compared to traditional virus
      isolation (VI) in cell culture. The T1 real-time RT-PCR had a higher sensitivity
      (93.4%) than the T2 real-time RT-PCR (42.6%) for detection of EAV RNA in semen.
      However, the T1 real-time RT-PCR was less sensitive (93.4%) than the World
      Organization for Animal Health (OIE)-prescribed VI test (gold standard). The
      sensitivity of both PCR assays was high (100.0% [T1] and 95.2% [T2]) for
      detecting EAV RNA in TCF. In light of the discrepancy in sensitivity between
      either real-time RT-PCR assay and VI, semen that is negative for EAV nucleic acid
      by real-time RT-PCR that is from an EAV-seropositive stallion should be confirmed
      free of virus by VI. Similarly, the presence of EAV in TCF samples that are VI
      positive but real-time RT-PCR-negative should be confirmed in a 1-way
      neutralization test using anti-EAV equine serum or by fluorescent antibody test
      using monoclonal antibodies to EAV. If the viral isolate is not identified as
      EAV, such samples should be tested for other equine viral pathogens. The results
      of this study underscore the importance of comparative evaluation and validation
      of real-time RT-PCR assays prior to their recommended use in a diagnostic setting
      for the detection and identification of specific infectious agents.

PMID- 18319427
TI  - Detection of Porcine reproductive and respiratory syndrome virus infection in
      porcine oral fluid samples: a longitudinal study under experimental conditions.
AB  - Isolation of Porcine reproductive and respiratory syndrome virus (PRRSV) from
      oral fluids was first reported in 1997. The objective of the present study was to
      determine whether PRRSV and/or anti-PRRSV antibodies were present in oral fluids
      at diagnostic levels. The level and duration of PRRSV and anti-PRRSV antibodies
      in serum and oral fluids was evaluated in 3 age groups of pigs (4, 8, or 12 weeks
      of age) inoculated with a type 2 (North American) PRRSV isolate. Serum, buccal
      swabs, and pen-based oral fluid samples were collected for 63 days following
      inoculation. Specimens were assayed for PRRSV by real-time quantitative reverse
      transcription polymerase chain reaction (qRT-PCR), and for anti-PRRSV antibodies
      by enzyme-linked immunosorbent assay (ELISA) and indirect fluorescent antibody
      test (IFAT). Porcine reproductive and respiratory syndrome virus was detected by
      real-time qRT-PCR in serum for approximately 5 weeks and in oral fluids for
      approximately 4 weeks postinoculation. Pig age at the time of inoculation had no
      effect on the quantity or duration of virus in oral fluid samples. Low levels of
      anti-PRRSV antibody were detected in oral fluid samples by ELISA and IFAT.
      Although the approach remains to be validated in the field, the results of this
      experiment suggest that pen-based oral fluid sampling could be an efficient, cost
      effective approach to PRRSV surveillance in swine populations.

PMID- 18319428
TI  - Comparison of histologic techniques for the diagnosis of bovine tuberculosis in
      the framework of eradication programs.
AB  - Rapid diagnosis of tuberculosis in cattle reacting positive in antemortem assays
      is crucial in countries where eradication programs are operated to confirm the
      presence of the infection in tuberculosis-free herds. This study evaluated the
      accuracy of histopathologic examination by hematoxylin and eosin and Ziehl
      Neelsen (ZN) staining applied in this framework, when suspected lesions are
      caused by low infectious doses and are detected in early stages of the disease.
      For this purpose, histologic methods were compared with mycobacterial culture as
      reference test on suspected lymph node samples from 173 cattle reacting positive
      in antemortem tests. Histopathology demonstrated high sensitivity (93.4%) and
      specificity (92.3%), while ZN sensitivity and specificity were respectively 33.9%
      and 100%. There was good agreement between histopathology and bacterial culture,
      suggesting that histopathologic examination is a reliable tool for rapid
      diagnosis in countries where active tuberculosis eradication programs allow the
      prompt identification and elimination of reactor cattle. Histopathology permits
      identification of typical mycobacterial lesions and its differentiation from
      other causes.

PMID- 18319429
TI  - Development and validation of an enzyme-linked immunosorbent assay for the
      diagnosis of porcine proliferative enteropathy.
AB  - The objective of this study was to develop an indirect enzyme-linked
      immunosorbent assay (ELISA) using a sonicated pure culture of Lawsonia
      intracellularis as the antigen (So-ELISA). A total of 332 serum samples,
      consisting of 232 experimentally infected animals and 100 animals naturally
      infected with L. intracellularis, were used to assess the diagnostic sensitivity.
      Three hundred and fifty-five sera from uninfected animals were used to determine
      the diagnostic specificity. The receiver operating characteristic and mean +3
      standard deviation of optical density (OD) values from uninfected animals were
      used for selecting cut-off points. The diagnostic accuracy of So-ELISA was
      considered to be high as the area under the curve index was 0.991 with 0.0029
      standard error. The optimal cut-off for So-ELISA was set at 0.45 OD with 89.8%
      sensitivity and 99.4% specificity based on a combination of good sensitivity and
      high specificity. No cross-reactivity was found in sera from pigs exposed to
      Brachyspira pilosicoli, B. hyodysenteriae, Campylobacter mucosalis, C. jejuni, or
      C. coli. Inter- and intracoefficient of variation of all control sera tested with
      So-ELISA was less than 10%. The observed agreements between So-ELISA and the
      immunoperoxidase monolayer assay tested with experimental challenge animals and
      field samples were 95.08% with 0.88 kappa and 90.65% with 0.74 kappa value,
      respectively. So-ELISA was able to detect the seroconversion of infected animals
      at 2 to 4 weeks after exposure to L. intracellularis. Based on the validation
      results, So-ELISA could be used as an alternative serology for proliferative
      enteropathy diagnosis.

PMID- 18319430
TI  - Comparison of flow cytometry and immunofluorescence microscopy for the detection
      of Giardia duodenalis in bovine fecal samples.
AB  - The performance of flow cytometry (FC) was compared with immunofluorescence
      microscopy (IM) for detection of Giardia duodenalis in bovine feces. Samples from
      36 adult dairy cows and 208 dairy calves were collected. Flow cytometry test
      characteristics were calculated using continuous, ordinal, and dichotomized
      results. Spearman correlation coefficients comparing the results of the 2 tests
      were 0.47 and 0.68 for cows and calves, respectively. Using IM as indicative of
      presence or absence of G. duodenalis cysts in each sample, likelihood ratios of
      FC results with 0, 1, and > or = 2 gated events indicated that samples with 1
      gated event were likely to be positive in the cows but not in the calves.
      Immunofluorescence microscopy detected G. duodenalis in 69.7% and 48.1% of cows
      and calves, respectively. When dichotomizing the FC results at a cut-off point of
      1 or 2 gated events, 46.3% and 19.9% of the cow and 51.9% and 35.1% of the calf
      samples, respectively, were classified as G. duodenalis-positive. Relative to IM,
      the sensitivity in the cows was 0.59 and 0.28, respectively, and 0.76 and 0.64,
      respectively, in the calves. At a cut-off point of 1, 65.7% and 73.1% of the cow
      and calf samples, respectively, were correctly classified in FC, and at a cut-off
      point of 2, 49.3% and 78.4% were correctly classified in the cows and calves,
      respectively. Flow cytometry was less sensitive than IM. Possible reasons and
      research needed to improve FC for G. duodenalis detection are discussed.

PMID- 18319431
TI  - Investigation of characteristics and factors associated with avian
      mycobacteriosis in zoo birds.
AB  - The objective of the current study was to identify factors associated with avian
      mycobacteriosis in zoo birds. Inventory data, population health records, and
      necropsy data from eligible birds in the Zoological Society of San Diego's (ZSSD)
      collection from 1991-2005 (n = 13,976) were used to describe disease incidence,
      prevalence, and postmortem findings. A matched case-control study was then
      conducted to identify factors describing demographic, temporal, and enclosure
      characteristics, along with move and exposure histories. Cases (disease-positive
      birds; n = 167) were matched in a 17 ratio with controls (disease-negative birds;
      n = 1169) of similar age and taxonomic grouping. Potential risk factors were
      evaluated using univariate and multivariable conditional logistic regression.
      Disease prevalence and incidence were estimated for the study period at 1.2% and
      3 cases/(1,000 bird-years at risk), respectively. Lesion characteristics and
      order prevalence are described. In the multivariable model, case birds were more
      likely to have been previously housed with a bird with mycobacterial disease
      involving the intestinal tract (odds ratio [OR] = 5.6, P < 0.01) or involving
      only nonintestinal sites (OR = 2.0, P < 0.01). Cases were more likely to have
      been imported into the collection than hatched at the ZSSD (OR = 4.2, P < 0.01).
      Cases were moved among ZSSD enclosures more than controls (OR = 1.1 for each
      additional move, P < 0.01). Findings will help guide future management of this
      disease for zoo bird populations.

PMID- 18319432
TI  - Frequency of yeasts and dermatophytes from healthy and diseased dogs.
AB  - The aim of this study was to investigate the presence of dermatophytes and yeasts
      in healthy and diseased dogs. A total of 633 samples were collected from 26
      healthy animals (104 samples), 131 with dermatitis (343 samples), 74 with otitis
      (148 samples), and 19 with ocular diseases (38 samples). Cultures from healthy
      animals were positive for Malassezia pachydermatis in 13.5% (7/52) of samples
      from skin, 42.3% (11/26) from ear, and 3.8% (1/26) from eye. Fungal growth was
      observed in 20.4% (70/343) samples from animals with dermatitis. Microsporum
      canis was the most isolated fungus (n = 39), followed by M. pachydermatis (n =
      30) and Malassezia sp. (n = 3). Of the 148 samples from dogs with otitis, 90
      (60.8%) were positive for M. pachydermatis, and of the clinical specimens from
      the conjunctiva of animals with ophthalmic disease, 2.6% (1/38) presented
      positive cultures for M. pachydermatis. Only 14.3% (2/14) of the positive
      cultures for M. pachydermatis and 40.9% (9/22) of those for M. canis were
      positive in the direct exam. Direct exams were positive in 84.3% (70/83) of the
      culture positive samples from affected ears of dogs with otitis. Malassezia
      pachydermatis may act as an aggravating factor in the occurrence of cutaneous
      diseases, or the isolation of M. canis may be associated with the onset of
      dermatophytosis. Fungal culture, rather than microscopic examination, should be
      used as the definitive diagnostic test for dermatomycoses and otitis.

PMID- 18319433
TI  - Adaptation and evaluation of a rapid test for the diagnosis of sheep scrapie in
      samples of rectal mucosa.
AB  - In recent publications, it was shown that disease-associated prion protein
      (PrP(d)) accumulates in the lymphoid tissue of the rectal mucosa of a high
      proportion of scrapie-infected sheep at clinical and preclinical stages,
      regardless of several host factors; PrP(d) can also be detected in biopsy
      specimens of rectal mucosa, with an increased probability proportional to age or
      incubation period and with an efficiency almost identical to that of tonsil
      biopsies. Rectal biopsies have the advantages of providing higher numbers of
      lymphoid follicles and of being simpler to perform, which makes them suitable for
      scrapie screening in the field. In biopsy samples, PrP(d) could be demonstrated
      by immunohistochemical (IHC) and Western immunoblotting methods, and the purpose
      of the present study was to optimize and evaluate a "rapid test" for the
      diagnosis of scrapie in rectal biopsy samples. The HerdChek CWD (chronic wasting
      disease) antigen EIA (enzyme immunoassay) test was chosen and, once optimized,
      provided specificity and sensitivity figures of 99.2% and 93.5%, respectively,
      compared with IHC results in the same samples obtained at a postmortem. The
      sensitivity of the assay increased from 82.1%, when a single rectal mucosa sample
      was tested to 99.4% for those sheep in which 3 or more samples were analyzed.
      Similarly, sensitivity values of the HerdChek CWD antigen EIA test on biopsy
      samples increased from 95% to 100% for sheep subjected to 1 or 2 sequential
      biopsies 4 months apart, respectively. Thus, a preclinical diagnosis of scrapie
      in live sheep can be achieved by a combination of a simple sampling procedure,
      which can be repeated several times with no detrimental effect for the animals,
      and a rapid and efficient laboratory method.

PMID- 18319434
TI  - A real-time polymerase chain reaction assay to detect single nucleotide
      polymorphisms at codon 171 in the prion gene for the genotyping of scrapie
      susceptibility in sheep.
AB  - The objective of this study was to report a reliable real-time polymerase chain
      reaction assay compatible with the Roche LightCycler 2.0 capable of genotyping
      sheep for scrapie susceptibility at codon 171. The single nucleotide
      polymorphisms (SNPs) in the prion protein gene in sheep that may govern
      resistance to scrapie at codon 171 encode for lysine (K), histidine (H),
      glutamine (Q), and arginine (R). A modified proteinase K method for leukocytes or
      whole blood was used to isolate genomic DNA from sheep blood. Fluoresentric
      developed and optimized primers and probes for the codon 171 SNP assay. The assay
      was initially validated using 218 determinations from whole blood of known
      genotypes with 100% correct identity. The assay was further validated through a
      whole-blood check test provided annually by the National Veterinary Services
      Laboratory with a correct identification rate of 100%. From January 2005 to
      December 2006, 3,672 samples from blood were genotyped at codon 171. The
      genotypes were QR(171) (n = 1,838, 50.05%), RR(171) (n = 1,423, 38.75%), QQ(171)
      (n = 407, 11.08%), HR(171) (n = 2, 0.05%), and HQ(171) (n = 2, 0.05%). The
      combination of this simple extraction method and the novel Fluoresentric assay is
      very accurate, is capable of identifying all 4 SNPs at codon 171 in one reaction,
      and has proven to be a useful tool for producers in their selective breeding
      programs.

PMID- 18319435
TI  - Culture of Piscirickettsia salmonis on enriched blood agar.
AB  - Piscirickettsia salmonis is the etiologic agent of piscirickettsiosis, an
      economically significant disease of fish. Isolation of P. salmonis by culturing
      on fish cell lines has been the standard technique since the initial isolation of
      the organism. The ability to grow P. salmonis on artificial media would relieve
      facilities of the cost of maintaining cell lines, permit isolation at fish
      culture sites with fewer contamination problems, and allow easier transport of
      isolates to diagnostic facilities for confirmation assays. This report describes
      the successful culture of P. salmonis on enriched blood agar.

PMID- 18319436
TI  - Antemortem versus postmortem methods for detection of betanodavirus in Senegalese
      sole (Solea senegalensis).
AB  - The suitability of nested reverse transcription polymerase chain reaction (nRT
      PCR) to detect betanodavirus in blood samples from naturally infected Senegalese
      sole (Solea senegalensis) was evaluated in comparison with other diagnostic
      methods. Results indicated that histologic examination of brain lesions could be
      regarded as the most consistent indicator of nodavirus infection in this species.
      The nRT-PCR showed low to moderate levels of detection; the best values were
      obtained in brain samples followed by blood samples. Inoculation of SSN-1 and SAF
      1 cells with fish samples did not cause cytopathic effect, although virus was
      detected by reverse transcription polymerase chain reaction in approximately 25%
      of the SSN-1 inoculated wells. The efficiency of detection of the viral genome
      was dramatically increased by the use of nRT-PCR, reaching 90.6% of positives in
      brain samples and 84.4% in blood samples. The sensitivity and the negative
      predictive value of nRT-PCR in blood samples were slightly lower than those
      obtained using brain samples. Nevertheless, it is suggested that the advantage of
      being able to perform diagnosis on live fish adequately counterbalances the
      slightly lower sensitivity of nRT-PCR on blood samples. This technique is
      proposed as a useful tool, not only for the selection of nodavirus-free breeders
      but also to check the fish status during ongrowing.

PMID- 18319437
TI  - The effects of formalin fixation and tissue embedding of bovine liver on copper,
      iron, and zinc analysis.
AB  - Veterinary analytical chemistry laboratories might be called upon to analyze
      formalin-fixed or paraffin-embedded tissue samples for trace minerals. The
      purpose of this study was to determine whether concentrations of copper (Cu),
      iron (Fe), and zinc (Zn) are comparable among fresh or frozen, formalin-fixed,
      and paraffin-embedded bovine liver samples on an as-received basis. Three liver
      sample subtypes (fresh or frozen, formalin-fixed, and paraffin-embedded) from 12
      cows were collected and analyzed for Cu, Fe, and Zn concentrations.
      Concentrations were measured by using inductively coupled argon plasma atomic
      emission spectroscopy. There was no significant difference in mineral
      measurements between fresh or frozen and formalin-fixed samples for Cu and Zn
      (both P > or = 0.052). The median concentration of Fe was lower in the fresh or
      frozen samples than in the formalin-fixed samples. However, for every pair of
      fresh or frozen and paraffin-embedded samples for all 3 minerals, the fresh or
      frozen sample had a lower measurement than the paraffin-embedded sample (all P =
      0.005). Differences in mineral measurements associated with tissue processing did
      not result in differences in classification (within or outside the reference
      range) for Fe. However, the classification of Cu and Zn was different up to 25%
      of the time with fresh or frozen versus formalin-fixed or embedded liver.
      Although Cu, Fe, and Zn concentrations attained from processed tissue may be
      useful, they must be evaluated with caution.

PMID- 18319438
TI  - Association of canine obesity with reduced serum levels of C-reactive protein.
AB  - The prevalence of obesity is increasing in dogs as well as in humans. C-reactive
      protein (CRP) is an important tool for the detection of inflammation and/or early
      tissue damage and is linked to obesity in humans. The objective of the present
      study was to determine if serum CRP levels are altered in obese dogs. Fifteen
      lean (control group) and 16 overweight (obese group) dogs were examined. Blood
      samples were collected under fasted conditions for serum determination of CRP,
      glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated
      that obese dogs were insulin resistant because serum insulin and insulin/glucose
      ratios were higher than in lean dogs (P < or = 0.05). Serum CRP concentrations
      were lower in obese dogs than in controls (P < or = 0.001). C-reactive protein
      was negatively correlated with insulin/glucose ratio (R = -0.42) and cholesterol
      (R = -0.39; P < or = 0.05). Furthermore, levels of cholesterol, triglycerides,
      and fructosamine were increased in the obese group compared with the control
      group. Based on these results, it can be postulated that CRP production is
      inhibited by obesity and insulin resistance in dogs.

PMID- 18319439
TI  - Identification of complex vertebral malformation carriers in Chinese Holstein.
AB  - Complex vertebral malformation (CVM) is a monogenic autosomal recessive
      hereditary defect of Holstein dairy cattle. It is caused by a point mutation from
      G to T at the nucleotide position 559 in bovine solute carrier family 35, member
      3 gene (SLC35A3), which changes the amino acid sequence of uridine 5'-diphosphate
      N-acetylglucosamine transporter protein from a valine to a phenylalanine in
      position 180. The elite U.S. Holstein sire Penstate Ivanhoe Star was identified
      as the common ancestor of the current CVM carriers. Because his offspring, mainly
      those of Carlin-M Ivanhoe Bell, were used in many countries, CVM has potentially
      spread into China. In the present study, using the polymerase chain reaction
      single-stranded conformational polymorphism (PCR-SSCP) technique, 10 CVM carriers
      were found among 68 at-risk Chinese Holstein bulls, and 282 carriers were found
      among 602 at-risk cows. The results of this study indicate that the CVM gene
      exists in the Chinese Holstein population.

PMID- 18319440
TI  - Development and field validation of a Mycoplasma iowae real-time polymerase chain
      reaction assay.
AB  - A Mycoplasma iowae real-time polymerase chain reaction (PCR) assay using primers
      and probes targeting the 16S rRNA gene was developed and field-validated in this
      study. The assay specifically identified M. iowae with a detection limit of 80
      colony-forming units (cfu) per turkey cloacal swab sample (3.2 cfu per PCR
      reaction). It was validated by testing 154 field turkey cloacal swab samples in
      parallel with culture isolation. The diagnostic sensitivity of the PCR was 97.6%,
      and the specificity was 95.5%. The real-time PCR developed in this study is a
      rapid, sensitive, and cost-effective alternative to culture isolation for
      detecting M. iowae from cloacal swab samples.

PMID- 18319441
TI  - Respiratory herpesvirus infection in two Indian Ringneck parakeets.
AB  - A flock of Indian Ringneck parakeets (Psittacula krameri manillensis) was
      imported to the United States from Australia. Soon after, 1 parakeet suddenly
      died, and a second parakeet died after a 2-day course of illness, which consisted
      of anorexia, lethargy, emaciation, and dyspnea. At necropsy, the affected birds
      had diffuse consolidation and red discoloration of the lungs, as well as
      thickened, congested air sacs. The microscopic examination revealed multifocal,
      necrotizing bronchitis, parabronchitis, and interstitial pneumonia. The lumen of
      the affected airways contained numerous, large syncytial cells with up to 15
      nuclei. The nuclei of these syncytial cells often contained large, eosinophilic
      inclusion bodies, consistent with herpesvirus. The epithelium of the trachea and
      air sacs was hypertrophied and contained syncytial cells with intranuclear
      inclusion bodies similar to the bronchi. In addition, a few intranuclear
      inclusion bodies were also present in the epithelial cells that line the air
      capillaries. On ultrastructural examination, the nuclei of degenerating
      epithelial cells contained clusters of viral nucleocapsid proteins and
      unenveloped, icosahedral, viral particles that were approximately 90 nm in
      diameter. In addition, some epithelial cells contained clusters of enveloped
      viral particles approximately 105 nm in diameter, within the cytocavitary
      network. These lesions are characteristic of those caused by respiratory
      herpesvirus of parakeets.

PMID- 18319442
TI  - Hemolytic-uremic syndrome in a postpartum mare concurrent with encephalopathy in
      the neonatal foal.
AB  - A postpartum mare and foal were presented for evaluation of fever and lethargy in
      the mare. The mare was diagnosed with endometritis and initially responded well
      to treatment. On the second day of hospitalization, the mare developed renal
      insufficiency characterized by oliguria, azotemia, hemolysis, and
      thrombocytopenia. Concurrently, the foal developed rapidly progressive central
      nervous system signs culminating in refractory seizures. Both animals failed to
      respond to treatment and were euthanized. Thrombotic microangiopathy involving
      glomeruli was evident on microscopic examination of the mare's kidneys.
      Microscopic evidence of brain edema was the principal postmortem finding in the
      foal. No specific etiology was confirmed in either case. Notably, Escherichia
      coli 0103:H2 was isolated from the mare's uterus and the gastrointestinal tracts
      of both animals. To the authors' knowledge, this is the first report in which an
      organism implicated as a cause of hemolytic-uremic syndrome was isolated from an
      animal with clinical signs and postmortem findings consistent with the disease.

PMID- 18319443
TI  - Hematogenous metastasis of embryonal rhabdomyosarcoma originating from skeletal
      muscle in a young dog.
AB  - An 8-month-old, intact male Golden Retriever with a history of left forelimb
      lameness for 2 months was presented to the Veterinary Medical Teaching Hospital
      of Konkuk University (Seoul, Korea). Results of a physical examination revealed a
      mass in the left axillary region. A thoracic radiography showed an osteolytic
      lesion in the scapula and the presence of a soft tissue density from the thoracic
      wall to the scapula. A computerized tomography revealed a mass invading into the
      scapula, and small nodules in the lung that suggested metastasis. At necropsy, a
      pale-yellow, irregular, firm, 8 x 10 x 5 cm mass extended from axillary region
      and destroyed the scapular. In addition, small nodules were noted in the lung. On
      microscopic examination, the mass consisted of round-to-oval cells, with
      eccentrically located hyperchromatic nuclei and eosinophilic cytoplasm in
      fibromyxoid stroma. Tumor cells were observed in blood vessels in the primary
      mass. Tumor cells strongly expressed vimentin, desmin, and myoglobin. In
      phosphotungstic acid-hematoxylin staining, cross-striations were detected in
      rhabdomyoblasts. In periodic acid-Schiff reaction, only a few cells were
      detected. The diagnosis was primary rhabdomyosarcoma of the appendicular muscle
      of a young dog. The tumor presumably originated in the skeletal muscle of the
      limb, invaded into the adjacent scapular bone, and metastasized to the lung.

PMID- 18319444
TI  - Community--academia partnerships to promote nutrition in the lower Mississippi
      delta: community members' perceptions of effectiveness, barriers, and factors
      related to success.
AB  - This study examined the perceptions of community members' engaged in community
      academia partnerships involved in developing nutrition interventions in three
      communities in the Lower Mississippi Delta. Perceptions on effectiveness of the
      partnerships were investigated. Six focus group interviews were conducted, with
      33 participants that included 27 females and 6 males. The data were analyzed by
      content coding. Emerging themes were identified and related to accomplishments,
      barriers to success, and factors related to success of the partnerships.
      Accomplishments included the establishment of active committees, positive changes
      in health behavior related to food choices, and participation in community
      events. Barriers to success included the slow pace of intervention
      implementation, difficulties with understanding the role of the community in the
      participatory research process, the decision-making processes, and project name
      recognition. Factors related to success were tangible benefits to the community,
      participation that was representative, simplification of the research process,
      and the decision-making processes.

PMID- 18319445
TI  - Entrepreneurship in health education and health promotion: five cardinal rules.
AB  - The nature of health education and health promotion (HE/HP) offers a fertile
      ground for entrepreneurial activity. As primary prevention of chronic diseases
      becomes a more central component of the health and/ or medical care continuum,
      entrepreneurial opportunities for health educators will continue to expand. The
      process used to design, implement, and evaluate health promotion and disease
      prevention has clear articulation with entrepreneurial, marketing management, and
      other business processes. Thus, entrepreneurs in HE/HP must be able to utilize
      business process to facilitate creative, new HE/HP business ideas. The purpose of
      this article is to weave theory and practical application into a primer on
      entrepreneurial applications in HE/HP. More specifically, the authors meld their
      prospective experiences and expertise to provide background thoughts on
      entrepreneurship in HE/HP and develop a framework for establishing an
      entrepreneurial venture in HE/HP. Five Cardinal Rules for Entrepreneurs in HE/HP
      are proposed.

PMID- 18319446
TI  - Changing stage of readiness for physical activity in Medicaid beneficiaries with
      physical impairments.
AB  - People with disabilities are more sedentary than the general population, putting
      them at risk for secondary conditions like diabetes. This study investigated the
      effectiveness of motivational interviewing (MI) for changing stage of readiness
      for physical activity, taking into account baseline stage of readiness and
      participation barriers. Study participants (n = 139 non-institutionalized,
      disabled Medicaid beneficiaries) were randomly assigned to either the treatment
      condition (MI) or a control condition (newsletter). Individuals receiving MI were
      more likely to move into the preparation stage of readiness (OR = 3.13).
      Regardless of treatment condition, individuals in the contemplation stage at
      baseline were more likely to move into preparation (OR = 5.53) and action stage
      (OR = 8.89). With regard to participation barriers, each unit increase in
      participants' ratings predicted a 4% to 5% reduction in likelihood of moving into
      either the preparation or action stage of readiness.

PMID- 18319447
TI  - Meeting report: cGMP matters.
AB  - The second messenger cyclic guanosine 3',5'-monophosphate (cGMP) controls many
      cellular functions ranging from growth to contractility. Generated from guanylyl
      cyclases in response to natriuretic peptides or nitric oxide, cGMP transduces its
      effects through a number of cGMP effectors, including cGMP-regulated
      phosphodiesterases and protein kinases. Drugs that modulate cGMP levels are
      emerging as promising therapies, particularly for cardiovascular disorders. This
      report summarizes new data on the molecular mechanisms, (patho)physiological
      relevance, and therapeutic potential of the cGMP signaling system that were
      presented at the 3rd cGMP meeting held in June 2007 in Dresden, Germany.

PMID- 18319448
TI  - List of new names and new combinations previously effectively, but not validly,
      published.
AB  - The purpose of this announcement is to effect the valid publication of the
      following effectively published new names and new combinations under the
      procedure described in the Bacteriological Code (1990 Revision). Authors and
      other individuals wishing to have new names and/or combinations included in
      future lists should send three copies of the pertinent reprint or photocopies
      thereof, or an electronic copy of the published paper, to the IJSEM Editorial
      Office for confirmation that all of the other requirements for valid publication
      have been met. It is also a requirement of IJSEM and the ICSP that authors of new
      species, new subspecies and new combinations provide evidence that types are
      deposited in two recognized culture collections in two different countries (i.e.
      documents certifying deposition and availability of type strains). It should be
      noted that the date of valid publication of these new names and combinations is
      the date of publication of this list, not the date of the original publication of
      the names and combinations. The authors of the new names and combinations are as
      given below, and these authors' names will be included in the author index of the
      present issue and in the volume author index. Inclusion of a name on these lists
      validates the publication of the name and thereby makes it available in
      bacteriological nomenclature. The inclusion of a name on this list is not to be
      construed as taxonomic acceptance of the taxon to which the name is applied.
      Indeed, some of these names may, in time, be shown to be synonyms, or the
      organisms may be transferred to another genus, thus necessitating the creation of
      a new combination.

PMID- 18319449
TI  - Notification that new names and new combinations have appeared in volume 57, part
      12, of the IJSEM.
AB  - This listing of names published in a previous issue of the IJSEM is provided as a
      service to bacteriology to assist in the recognition of new names and new
      combinations. This procedure was proposed by the Judicial Commission [Minute
      11(ii), Int J Syst Bacteriol 41 (1991), p. 185]. The names given herein are
      listed according to the Rules of priority (i.e. page number and order of valid
      publication of names in the original articles). Taxonomic opinions included in
      this List (i.e. the creation of synonyms or the emendation of circumscriptions)
      cannot be considered as validly published nor, in any other way, approved by the
      International Committee on Systematics of Prokaryotes and its Judicial
      Commission.

PMID- 18319450
TI  - Chryseobacterium aquaticum sp. nov., isolated from a water reservoir.
AB  - Strains 10-46(T) and 10-106 were isolated from a water reservoir in Korea. They
      were Gram-negative, non-motile, non-spore-forming rods, produced yellow-pigmented
      colonies on nutrient agar, contained MK-6 as the predominant menaquinone and 15 :
      0 iso and 17 : 0 iso 3-OH as the major fatty acids and had polar lipid profiles
      consisting of phosphatidylethanolamine and several unknown aminolipids.
      Phylogenetic analysis, based on 16S rRNA gene sequencing, showed that the strains
      were closely related to Chryseobacterium indoltheticum ATCC 27950(T),
      Chryseobacterium scophthalmum LMG 13028(T) and Chryseobacterium soldanellicola
      KCTC 12382(T) (96.9, 96.8 and 96.7 % sequence similarity, respectively) and
      formed a separate lineage within the genus Chryseobacterium. The combined
      genotypic and phenotypic data supported the conclusion that the strains represent
      a novel species of the genus Chryseobacterium, for which the name
      Chryseobacterium aquaticum sp. nov. is proposed. The type strain is 10-46(T)
      (=KCTC 12483(T) =CECT 7302(T)).

PMID- 18319451
TI  - Sanguibacter soli sp. nov., isolated from soil of a ginseng field.
AB  - A Gram-positive, non-spore-forming, rod-shaped, motile bacterium, designated
      strain DCY22(T), was isolated from soil of a ginseng field in South Korea and
      characterized in order to determine its taxonomic position. 16S rRNA gene
      sequence analysis revealed that strain DCY22(T) belonged within the family
      Sanguibacteraceae, and highest levels of sequence similarity were found with
      Sanguibacter marinus 1-19(T) (96.8 %), Sanguibacter suarezii ST-26(T) (96.0 %),
      Sanguibacter inulinus ST-50(T) (95.9 %), Sanguibacter keddieii ST-74(T) (95.5 %),
      Terrabacter terrae PPLB(T) (94.0 %) and Terrabacter tumescens DSM 20308(T) (93.8
      %). Chemotaxonomic investigations revealed that strain DCY22(T) possessed
      menaquinone MK-9, a common feature of members of the genus Sanguibacter.
      Predominant fatty acids were unknown ECL 13.961 (45.81 %), 17 : 0 anteiso (23.46
      %), 18 : 0 iso (15.42 %) and unknown ECL 14.966 (8.70 %). The results of
      physiological and biochemical tests clearly demonstrated that strain DCY22(T)
      represents a novel species of the genus Sanguibacter, for which the name
      Sanguibacter soli sp. nov. is proposed. The type strain is DCY22(T) (=KCTC
      13155(T)=JCM 14841(T)).

PMID- 18319452
TI  - Tenacibaculum adriaticum sp. nov., from a bryozoan in the Adriatic Sea.
AB  - A rod-shaped, translucent yellow-pigmented, Gram-negative bacterium, strain
      B390(T), was isolated from the bryozoan Schizobrachiella sanguinea collected in
      the Adriatic Sea, near Rovinj, Croatia. 16S rRNA gene sequence analysis indicated
      affiliation to the genus Tenacibaculum, with sequence similarity levels of 94.8
      97.3 % to type strains of species with validly published names. It grew at 5-34
      degrees C, with optimal growth at 18-26 degrees C, and only in the presence of
      NaCl or sea salts. In contrast to other type strains of the genus, strain B390(T)
      was able to hydrolyse aesculin. The predominant menaquinone was MK-6 and major
      fatty acids were iso-C(15 : 0), iso-C(15 : 0) 3-OH and iso-C(15 : 1). The DNA G+C
      content was 31.6 mol%. DNA-DNA hybridization and comparative physiological tests
      were performed with type strains Tenacibaculum aestuarii JCM 13491(T) and
      Tenacibaculum lutimaris DSM 16505(T), since they exhibit 16S rRNA gene sequence
      similarities above 97 %. These data, as well as phylogenetic analyses, suggest
      that strain B390(T) (=DSM 18961(T) =JCM 14633(T)) should be classified as the
      type strain of a novel species within the genus Tenacibaculum, for which the name
      Tenacibaculum adriaticum sp. nov. is proposed.

PMID- 18319453
TI  - Sneathiella glossodoripedis sp. nov., a marine alphaproteobacterium isolated from
      the nudibranch Glossodoris cincta, and proposal of Sneathiellales ord. nov. and
      Sneathiellaceae fam. nov.
AB  - A novel marine bacterium, designated strain MKT133(T), was isolated from the foot
      epidermis of a nudibranch, Glossodoris cincta (Mollusca), collected in seawater
      off the coast of Japan at a depth of 4 m. This bacterium was Gram-negative,
      motile, mesophilic and strictly aerobic, with small rod-shaped cells. Colonies of
      the strain after 4-5 days incubation on marine agar 2216 at 30 degrees C were
      less than 1 mm in diameter. The strain required salt for growth and contained Q
      10 as the predominant respiratory quinone, C(18 : 1) omega 7c, C(16 : 0) and C(17
      : 1) as major cellular fatty acids and C(14 : 0) 3-OH as a hydroxy fatty acid.
      16S rRNA gene sequence analysis showed that the isolate had highest similarity to
      Sneathiella chinensis, with 97.2 % sequence similarity to the type strain. Our
      phylogenetic analysis also revealed that this clade represents a distinct lineage
      and forms a deep branch with less than 90 % 16S rRNA gene sequence similarity to
      the members of the eight known orders within the Alphaproteobacteria. Sufficient
      differences exist to distinguish this strain from Sneathiella chinensis. The name
      Sneathiella glossodoripedis sp. nov. is proposed, with the type strain MKT133(T)
      (=IAM 15419(T) =KCTC 12842(T)). The novel order Sneathiellales ord. nov. and
      family Sneathiellaceae fam. nov. are proposed for the distinct phyletic line
      represented by the genus Sneathiella.

PMID- 18319454
TI  - Differential patterns of evolution and distribution of the symbiotic behaviour in
      nostocacean cyanobacteria.
AB  - Many cyanobacteria commonly identified as belonging to the genus Nostoc are well
      known cyanobionts (symbionts) of a wide variety of plants and fungi. They form
      symbioses with bryophytes, pteridophytes, gymnosperms and angiosperms that are
      considerably different in the type of reciprocal interaction between the host and
      the cyanobiont. The phylogenetic and taxonomic relationships among cyanobionts
      isolated from different hosts and Nostoc strains isolated from free-living
      conditions are still not well understood. We compared phylogeny and morphology of
      symbiotic cyanobacteria originating from different host plants (genera Gunnera,
      Azolla, Cycas, Dioon, Encephalartos, Macrozamia and Anthoceros) with free-living
      Nostoc isolates originating from different habitats. After preliminary clustering
      with ARDRA (amplified rDNA restriction analysis), phylogeny was reconstructed on
      the basis of 16S rRNA gene sequences and compared with morphological
      characterization, obtaining several supported clusters. Two main Nostoc clusters
      harboured almost all cyanobionts of Gunnera, Anthoceros and of several cycads,
      together with free-living strains of the species Nostoc muscorum, Nostoc
      calcicola, Nostoc edaphicum, Nostoc ellipsosporum and strains related to Nostoc
      commune. We suggest that the frequent occurrence of symbiotic strains within
      these clusters is explained by the intensive hormogonia production that was
      observed in many of the strains studied. However, no evidence for discrimination
      between symbiotic and free-living strains, either by molecular or morphological
      approaches, could be found. Sequences of Azolla cyanobiont filaments, taken
      directly from leaf cavities, clustered tightly with sequences from the planktic
      cyanobacterium Cylindrospermopsis raciborskii, from the benthic Anabaena
      cylindrica 133 and from Anabaena oscillarioides HINDAK 1984/43, with high
      bootstrap values. The phylogenetic analysis showed that two distinct patterns of
      evolution of symbiotic behaviour might exist for the nostocacean cyanobacteria,
      one leading to symbioses of Nostoc species with a wide variety of plants, the
      other leading to the association of a unique cyanobacterial type with the water
      fern Azolla.

PMID- 18319455
TI  - Burkholderia sediminicola sp. nov., isolated from freshwater sediment.
AB  - A Gram-negative, motile and rod-shaped bacterium, designated HU2-65W(T), was
      isolated from freshwater sediment. The strain possessed ubiquinone 8 as the
      predominant isoprenoid quinone and contained major amounts of omega7-cis
      octadecenoic acid and hexadecanoic acid in its cell envelope, which are
      properties shared by members of the genus Burkholderia. On the basis of 16S rRNA
      gene sequence similarity, strain HU2-65W(T) was most closely related to the type
      strain of Burkholderia xenovorans (98.4 %). The DNA G+C content of strain HU2
      65W(T) was 61.2 mol%, and DNA-DNA relatedness values to type strains of closely
      related species were found to be much lower than 70 %, indicating that the strain
      represents a separate genomic species within the genus Burkholderia. Strain HU2
      65W(T) was also differentiated from other species of the genus by physiological
      and biochemical characteristics. Consequently, strain HU2-65W(T) is considered to
      represent a single, novel species of the genus Burkholderia, for which the name
      Burkholderia sediminicola sp. nov. is proposed, with the type strain HU2-65W(T)
      (=KCTC 22086(T) =LMG 24238(T)).

PMID- 18319456
TI  - Saccharomonospora saliphila sp. nov., a halophilic actinomycete from an Indian
      soil.
AB  - A Gram-positive, moderately halophilic actinomycete strain, designated YIM
      90502(T), was isolated from a sample of muddy soil collected from Gulbarga,
      Karnataka Province, India, and subjected to a polyphasic taxonomical analysis.
      The isolate grew optimally at 28 degrees C and in the presence of 10 % (w/v)
      NaCl. The isolate was characterized chemotaxonomically as having meso
      diaminopimelic acid in the cell-wall peptidoglycan and galactose and arabinose as
      whole-cell sugars. The predominant menaquinone was MK-9(H(4)), while MK-8(H(4))
      was found in smaller amounts. The phospholipids were phosphatidylinositol,
      phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The
      major fatty acids were iso-C(16 : 0) (49.2 %) and C(17 : 1)omega6c (9.1 %). The
      DNA G+C content of the isolate was 71.8 mol%. A phylogenetic tree based on 16S
      rRNA gene sequences showed that the isolate fell within the evolutionary
      radiation encompassed by the genus Saccharomonospora. 16S rRNA gene sequence
      similarity between strain YIM 90502(T) and the type strains of Saccharomonospora
      species ranged from 92.42 % (with Saccharomonospora xinjiangensis CCTCC AA
      97021(T)) to 97.45 % (with Saccharomonospora azurea KCTC 9693(T)). Levels of DNA
      DNA relatedness between strain YIM 90502(T) and S. azurea KCTC 9693(T),
      Saccharomonospora halophila DSM 44411(T) and Saccharomonospora paurometabolica
      DSM 44619(T) were 46.0, 41.0 and 42.5 %, respectively. On the basis of
      phenotypic, phylogenetic and genotypic data, strain YIM 90502(T) was classified
      in the genus Saccharomonospora as a member of a novel species, for which the name
      Saccharomonospora saliphila sp. nov. is proposed, with YIM 90502(T) (=KCTC
      19234(T) =DSM 45087(T)) as the type strain.

PMID- 18319457
TI  - Brevibacterium album sp. nov., a novel actinobacterium isolated from a saline
      soil in China.
AB  - A novel Gram-positive, rod-shaped actinobacterium, designated strain YIM
      90718(T), was isolated from a saline soil in Xinjiang province, north-west China,
      and subjected to polyphasic taxonomy. The peptidoglycan type was A1gamma and the
      cell-wall sugars contained galactose. Phospholipids were phosphatidylglycerol and
      diphosphatidylglycerol. The predominant menaquinone was MK-8(H(2)). The major
      fatty acids were anteiso-C(15 : 0), anteiso-C(17 : 0) and iso-C(15 : 0). All of
      these chemotaxonomic data assigned the new isolate YIM 90718(T) consistently to
      the genus Brevibacterium. Phylogenetic analysis based on 16S rRNA gene sequences
      revealed that strain YIM 90718(T) formed a distinct phyletic lineage in the genus
      Brevibacterium and showed the highest sequence similarity (96.2 %) to
      Brevibacterium samyangense SST-8(T) and low similarity (<95.5 %) to other species
      of the genus Brevibacterium. On the based of the polyphasic evidence, a novel
      species, Brevibacterium album sp. nov., is proposed, with the type strain YIM
      90718(T) (=DSM 18261(T) =KCTC 19173(T) =CCTCC AB 206112(T)).

PMID- 18319458
TI  - Nevskia soli sp. nov., isolated from soil cultivated with Korean ginseng.
AB  - A Gram-negative bacterium, designated strain GR15-1(T), was isolated from a field
      cultivated with Korean ginseng. Cells were strictly aerobic, motile with
      multipolar flagella and rod-shaped. The strain grew optimally at 25-28 degrees C
      and pH 6.0-7.0. The predominant fatty acids of strain GR15-1(T) were C(18 :
      1)omega7c, C(16 : 0) and summed feature 2 (C(14 : 0) 3-OH and/or iso-C(16 : 1)
      I). The major isoprenoid quinone was ubiquinone 8. The G+C content of the genomic
      DNA was 63.9 mol%. Phylogenetic analysis showed that strain GR15-1(T) formed a
      phyletic cluster with Nevskia ramosa Soe1(T), with a 16S rRNA gene sequence
      similarity of 96.8 %. Based on phenotypic, chemotaxonomic and phylogenetic
      features, strain GR15-1(T) represents a novel species within the genus Nevskia,
      for which the name Nevskia soli sp. nov. is proposed. The type strain is GR15
      1(T) (=KACC 11703(T) =DSM 19509(T)).

PMID- 18319459
TI  - Veillonella rogosae sp. nov., an anaerobic, Gram-negative coccus isolated from
      dental plaque.
AB  - Strains of a novel anaerobic, Gram-negative coccus were isolated from the supra
      gingival plaque of children. Independent strains from each of six subjects were
      shown, at a phenotypic level and based on 16S rRNA gene sequencing, to be members
      of the genus Veillonella. Analysis revealed that the six strains shared 99.7 %
      similarity in their 16S rRNA gene sequences and 99.0 % similarity in their rpoB
      gene sequences. The six novel strains formed a distinct group and could be
      clearly separated from recognized species of the genus Veillonella of human or
      animal origin. The novel strains exhibited 98 and 91 % similarity to partial 16S
      rRNA and rpoB gene sequences of Veillonella parvula ATCC 10790(T), the most
      closely related member of the genus. The six novel strains could be
      differentiated from recognized species of the genus Veillonella based on partial
      16S rRNA and rpoB gene sequencing. The six novel strains are thus considered to
      represent a single novel species of the genus Veillonella, for which the name
      Veillonella rogosae sp. nov. is proposed. The type strain is CF100(T) (=CCUG
      54233(T)=DSM 18960(T)).

PMID- 18319460
TI  - Spongiibacter marinus gen. nov., sp. nov., a halophilic marine bacterium isolated
      from the boreal sponge Haliclona sp. 1.
AB  - Strain HAL40b(T) was isolated from the marine sponge Haliclona sp. 1 collected at
      the Sula Ridge off the Norwegian coast and characterized by physiological,
      biochemical and phylogenetic analyses. The isolate was a small rod with a polar
      flagellum. It was aerobic, Gram-negative and oxidase- and catalase-positive.
      Optimal growth was observed at 20-30 degrees C, pH 7-9 and in 3 % NaCl. Substrate
      utilization tests were positive for arabinose, Tween 40 and Tween 80. Enzyme
      tests were positive for alkaline phosphatase, esterase lipase (C8), leucine
      arylamidase, acid phosphatase, naphthol-AS-BI-phosphohydrolase and N-acetyl-beta
      glucosaminidase. The predominant cellular fatty acid was C(17 : 1) omega8,
      followed by C(17 : 0) and C(18 : 1) omega7. Analysis by matrix-assisted laser
      desorption/ionization time-of-flight MS was used to characterize the strain,
      producing a characteristic low-molecular-mass protein pattern that could be used
      as a fingerprint for identification of members of this species. The DNA G+C
      content was 69.1 mol%. Phylogenetic analysis supported by 16S rRNA gene sequence
      comparison classified the strain as a member of the class Gammaproteobacteria.
      Strain HAL40b(T) was only distantly related to other marine bacteria including
      Neptunomonas naphthovorans and Marinobacter daepoensis (type strain sequence
      similarity >90 %). Based on its phenotypic, physiological and phylogenetic
      characteristics, it is proposed that the strain should be placed into a new genus
      as a representative of a novel species, Spongiibacter marinus gen. nov., sp.
      nov.; the type strain of Spongiibacter marinus is HAL40b(T) (=DSM 17750(T) =CCUG
      54896(T)).

PMID- 18319461
TI  - Classification of halo(alkali)philic and halo(alkali)tolerant methanotrophs
      provisionally assigned to the genera Methylomicrobium and Methylobacter and
      emended description of the genus Methylomicrobium.
AB  - The taxonomic positions of four aerobic, obligately halo(alkali)philic/-tolerant,
      methanotrophic bacteria previously affiliated with the genera Methylobacter
      ('Methylobacter alcaliphilus' strains 20Z and 5Z) and Methylomicrobium
      (Methylomicrobium strains AMO1 and NI) were investigated. Phylogenetic analysis
      of 16S rRNA gene sequences indicated that the strains form a separate branch
      within the type I methanotrophic bacteria and are closely related to
      Methylomicrobium pelagicum. DNA-DNA hybridization data revealed relatively low
      levels of relatedness of Methylomicrobium sp. AMO1 and Methylomicrobium sp. N1
      with each other and with previously described species of the genera
      Methylomicrobium and Methylobacter (<55 %), indicating that they may represent
      novel species. Based on the results presented here and on previously reported
      morphological and physiological characteristics, we classify these halotolerant
      and halophilic methanotrophic strains as representing novel species within the
      genus Methylomicrobium: Methylomicrobium alcaliphilum sp. nov. (type strain
      20Z(T) =VKM B-2133(T) =NCIMB 14124(T); reference strain 5Z =VKM B-2180),
      Methylomicrobium japanense sp. nov. (type strain NI(T) =VKM B-2462(T) =FERM BP
      5633(T) =NBRC 103677(T)) and Methylomicrobium kenyense sp. nov. (type strain
      AMO1(T) =NCCB 97157(T) =NCIMB 13566(T) =VKM B-2464(T)). The genus
      Methylomicrobium has been emended in its description.

PMID- 18319462
TI  - Phycicoccus dokdonensis sp. nov., isolated from soil.
AB  - A Gram-positive, non-motile, coccoid-shaped bacterium, designated strain DS-8(T),
      was isolated from soil from Dokdo, Korea, and its taxonomic position was
      investigated by using a polyphasic study. Strain DS-8(T) grew optimally at 30
      degrees C and pH 6.5-7.5 in the presence of 0.5-1.0 % (w/v) NaCl. A neighbour
      joining phylogenetic tree based on 16S rRNA gene sequences showed that strain DS
      8(T) joined the type strain of Phycicoccus jejuensis, with a bootstrap resampling
      value of 92.5 %, and shared 96.5 % 16S rRNA gene sequence similarity with P.
      jejuensis. The cell-wall peptidoglycan type was based on meso-diaminopimelic acid
      and the acyl type of the muramic acid was acetyl. The predominant menaquinone was
      MK-8(H(4)). The major fatty acids were iso-C(15 : 0) and iso-C(16 : 0). Major
      polar lipids detected in strain DS-8(T) were phosphatidylinositol,
      phosphatidylglycerol, diphosphatidylglycerol and two unidentified phospholipids.
      The DNA G+C content was 70.7 mol%. DNA-DNA relatedness data and differential
      phenotypic properties, together with the phylogenetic distinctiveness, revealed
      that strain DS-8(T) differs from P. jejuensis. On the basis of the data obtained,
      strain DS-8(T) is considered to represent a novel species of the genus
      Phycicoccus, for which the name Phycicoccus dokdonensis sp. nov. is proposed. The
      type strain is DS-8(T) (=KCTC 19248(T)=CCUG 54521(T)).

PMID- 18319463
TI  - Nubsella zeaxanthinifaciens gen. nov., sp. nov., a zeaxanthin-producing bacterium
      of the family Sphingobacteriaceae isolated from freshwater.
AB  - A yellow-pigmented, Gram-negative, strictly aerobic, rod-shaped bacterium (TDMA
      5(T)) was isolated from a freshwater sample collected at Misasa (Tottori, Japan).
      The DNA G+C content was 38.6 mol%. Major fatty acids were iso-C(15 : 0), iso-C(17
      : 0) 3-OH and summed feature 4 (iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c). MK-7
      was the predominant respiratory quinone. Zeaxanthin was the major carotenoid
      pigment produced; flexirubin-type pigments were not produced. TDMA-5(T) was
      sensitive to gamma-irradiation. The strain degraded gelatin, casein, starch,
      Tween 80 and DNA. Phylogenetic analysis based on the 16S rRNA gene sequence
      placed TDMA-5(T) in a distinct lineage in the family Sphingobacteriaceae, sharing
      89.4-93.4 % sequence similarity with members of the nearest genus Pedobacter.
      Strain TDMA-5(T) could be distinguished from the other members of the family
      Sphingobacteriaceae by a number of chemotaxonomic and phenotypic characteristics.
      Based on its unique phenotypic, genotypic and phylogenetic features, strain TDMA
      5(T) represents a novel genus and species, for which the name Nubsella
      zeaxanthinifaciens gen. nov., sp. nov. is proposed. The type strain of Nubsella
      zeaxanthinifaciens is TDMA-5(T) (=NBRC 102579(T) =CCUG 54348(T)).

PMID- 18319464
TI  - Chryseobacterium aquifrigidense sp. nov., isolated from a water-cooling system.
AB  - A non-motile, yellow-pigmented bacterium, designated strain CW9(T), was isolated
      from a water-cooling system in Gwangyang, Republic of Korea. The cells were Gram
      negative, catalase- and oxidase-positive, short rods. The major fatty acids were
      iso-C(15 : 0) (45.5 %), iso-C(17 : 1)omega9c (14.4 %), iso-C(17 : 0) 3-OH (13.0
      %) and summed feature 3 (comprising iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c;
      8.8 %). The DNA G+C content was 35.6 mol%. A phylogenetic tree based on 16S rRNA
      gene sequences showed that strain CW9(T) formed a lineage within the genus
      Chryseobacterium and was closely related to Chryseobacterium gleum ATCC 35910(T)
      (98.4 % sequence similarity) and Chryseobacterium indologenes ATCC 29897(T) (97.8
      % sequence similarity). Phenotypic characteristics and DNA-DNA relatedness data
      served to distinguish strain CW9(T) from these two species. On the basis of the
      evidence presented in this study, strain CW9(T) represents a novel species of the
      genus Chryseobacterium, for which the name Chryseobacterium aquifrigidense sp.
      nov. is proposed. The type strain is CW9(T) (=KCTC 12894(T)=JCM 14756(T)).

PMID- 18319465
TI  - Paenibacillus woosongensis sp. nov., a xylanolytic bacterium isolated from forest
      soil.
AB  - A novel xylan-degrading bacterium, YB-45(T), was isolated from forest soil. The
      organism is a facultatively anaerobic, Gram-variable, motile, endospore-forming,
      rod-shaped bacterium. It grew optimally at 37 degrees C and pH 7.5 in the
      presence of 3 % (w/v) NaCl. The predominant cellular fatty acids were anteiso
      C(15 : 0), iso-C(15 : 0) and C(16 : 0). The DNA G+C content was 51.7 mol% and the
      predominant menaquinone was MK-7. Growth was observed with many carbohydrates,
      including xylan, as sole carbon sources. Strain YB-45(T) produces a wide variety
      of hydrolytic enzymes, such as xylanase, cellulase, amylase, beta-mannanase, beta
      mannosidase, beta-xylosidase, alpha-galactosidase, beta-galactosidase and beta
      glucosidase. Phylogenetic analyses based on 16S rRNA gene sequences showed that
      strain YB-45(T) belongs to the genus Paenibacillus, sharing sequence similarity
      that was <96 %. It was related most closely to Paenibacillus jamilae DSM
      13815(T), with 95.7 % sequence similarity. On the basis of morphological,
      chemotaxonomic, physiological and phylogenetic properties, strain YB-45(T)
      represents a novel species of the genus Paenibacillus, for which the name
      Paenibacillus woosongensis sp. nov. is proposed. The type strain is YB-45(T)
      (=KCTC 3953(T)=DSM 16971(T)).

PMID- 18319466
TI  - Identification of vibrio cholerae and vibrio mimicus by multilocus sequence
      analysis (MLSA).
AB  - Vibrio cholerae and Vibrio mimicus have similar phenotypes and genomes making
      rapid differentiation of these two species difficult. The first standard
      multilocus sequence analysis (MLSA) scheme for the identification of these
      species is described. A collection of 45 representative isolates from different
      geographical regions and hosts was examined using segments of the housekeeping
      genes pyrH, recA and rpoA. Overall, the closest phylogenetic neighbours of these
      species were Vibrio furnissii and Vibrio fluvialis. V. cholerae and V. mimicus
      formed separate species clusters on the basis of each gene, suggesting that these
      genes are useful as identification markers. These species clusters arose by the
      accumulation of point mutations. The pyrH gene showed the highest resolution for
      differentiating V. cholerae and V. mimicus. The maximum interspecies pyrH gene
      sequence similarity was 91 %. Clearly, V. mimicus strains were more heterogeneous
      than V. cholerae strains at the three loci. It is suggested that vibrio species
      may be defined on the basis of MLSA data. A vibrio species was defined as a group
      of strains forming a monophyletic group on the basis of these loci and with an
      intraspecific sequence similarity of at least 95 %. V. cholerae and V. mimicus
      isolates can be readily identified through the open database resource 'The
      Taxonomy of Vibrios' (http://www.taxvibrio.lncc.br/).

PMID- 18319467
TI  - Halobacillus seohaensis sp. nov., isolated from a marine solar saltern in Korea.
AB  - A Gram-positive or Gram-variable, motile, moderately halophilic, rod-shaped
      bacterial strain, ISL-50(T), was isolated from a marine solar saltern in Korea
      and subjected to a polyphasic taxonomic study. Strain ISL-50(T) grew optimally at
      pH 7.0-8.0 and 37 degrees C in the presence of 8 % (w/v) NaCl. Phylogenetic
      analyses based on 16S rRNA gene sequences showed that strain ISL-50(T) belonged
      to the genus Halobacillus. Strain ISL-50(T) exhibited 16S rRNA gene sequence
      similarity values of 95.3-98.2 % with respect to the type strains of recognized
      Halobacillus species. The cell-wall peptidoglycan was based on meso
      diaminopimelic acid, the predominant menaquinone was MK-7 and the major fatty
      acids were anteiso-C(15 : 0) and anteiso-C(17 : 0). The DNA G+C content was 39.3
      mol%. DNA-DNA relatedness data and differential phenotypic properties revealed
      that strain ISL-50(T) was distinguishable from the recognized Halobacillus
      species. On the basis of phenotypic, chemotaxonomic, phylogenetic and genetic
      data, strain ISL-50(T) represents a novel species of the genus Halobacillus, for
      which the name Halobacillus seohaensis sp. nov. is proposed. The type strain is
      ISL-50(T) (=KCTC 13145(T)=CCUG 54358(T)).

PMID- 18319468
TI  - Saccharopolyspora cebuensis sp. nov., a novel actinomycete isolated from a
      Philippine sponge (Porifera).
AB  - The taxonomic status of a marine actinomycete isolated from the sponge Haliclona
      sp. collected from Cebu, Philippines, was established using both phenotypic and
      genotypic data. Strain SPE 10-1(T) exhibited chemotaxonomic and morphological
      characteristics that were consistent with those of members of the genus
      Saccharopolyspora. It showed a strict requirement for salt and is the first
      obligate marine bacterium of the genus Saccharopolyspora to be isolated. The
      principal isoprenoid quinone detected was MK-9(H(4)). The fatty acid pattern
      consisted mainly of terminally branched iso and anteiso fatty acids. The DNA G+C
      content was 72.6 mol%. Analysis of the 16S rRNA gene sequence supported
      affiliation of the strain with the genus Saccharopolyspora; the type strain of
      Saccharopolyspora gregorii was the closest phylogenetic relative (96 % sequence
      similarity). Sequence similarities of strain SPE 10-1(T) to other type strains of
      this genus were 93-95 %. It is proposed that strain SPE 10-1(T) should be
      classified in the genus Saccharopolyspora as a representative of
      Saccharopolyspora cebuensis sp. nov. The type strain of Saccharopolyspora
      cebuensis is SPE 10-1(T) (=DSM 45019(T)=CIP 109355(T)).

PMID- 18319469
TI  - Devosia geojensis sp. nov., isolated from diesel-contaminated soil in Korea.
AB  - A Gram-negative, strictly aerobic, non-spore-forming bacterium, designated strain
      BD-c194(T), was isolated from diesel-contaminated soil in Geoje, Korea. The cells
      were short, motile rods with single polar flagella. Growth of strain BD-c194(T)
      was observed between 15 and 45 degrees C (optimally at 30-35 degrees C) and
      between pH 6.0 and 9.5 (optimally at pH 7.5-9.0). The predominant fatty acids
      were 11-methyl C(18 : 1)omega7c, C(16 : 0), C(18 : 1)omega7c, C(18 : 0) and an
      unknown fatty acid (equivalent chain-length 18.814); a large amount of
      phosphatidylglycerol and a small amount of diphosphatidylglycerol were present as
      polar lipids. The G+C content of the genomic DNA was 60.8 mol% and the major
      isoprenoid quinone was Q-10. A comparative 16S rRNA gene sequence analysis showed
      that strain BD-c194(T) formed a well-defined phyletic lineage within the genus
      Devosia (with 100 % bootstrap support). The levels of 16S rRNA gene sequence
      similarity with respect to the type strains of other Devosia species ranged from
      95.0 to 96.1 %. On the basis of chemotaxonomic data and molecular properties,
      strain BD-c194(T) represents a novel species within the genus Devosia, for which
      the name Devosia geojensis sp. nov. is proposed. The type strain is BD-c194(T)
      (=KCTC 22082(T) =DSM 19414(T)).

PMID- 18319470
TI  - Marinobacter pelagius sp. nov., a moderately halophilic bacterium.
AB  - A Gram-negative, aerobic, neutrophilic, moderately halophilic bacterial strain,
      HS225(T), was isolated from seawater samples around the Zhoushan Archipelago,
      Zhejiang Province, China. The isolate grew optimally in media with 5.0 % NaCl, at
      pH 7.0-8.0 and at 25-30 degrees C. The predominant fatty acids were C(16 :
      0)omega9c, C(16 : 0), C(12 : 0) 3-OH and C(18 : 1)omega9c. The genomic DNA G+C
      content was 59.0 mol%. Based on 16S rRNA gene sequence analysis, the isolate was
      found to be affiliated to the genus Marinobacter. Strain HS225(T) exhibited
      closest phylogenetic affinity to Marinobacter koreensis DD-M3(T) (98.1 % 16S rRNA
      gene sequence similarity). DNA-DNA relatedness data and DNA G+C contents as well
      as physiological and biochemical test results allowed the genotypic and
      phenotypic differentiation of strain HS225(T) from closely related species.
      Therefore, it is proposed that strain HS225(T) represents a novel species of the
      genus Marinobacter, for which the name Marinobacter pelagius sp. nov. is
      proposed. The type strain is HS225(T) (=CGMCC 1.6775(T) =JCM 14804(T)).

PMID- 18319471
TI  - Mycobacterium senuense sp. nov., a slowly growing, non-chromogenic species
      closely related to the Mycobacterium terrae complex.
AB  - A previously undescribed, slowly growing, non-chromogenic mycobacterium, isolated
      from a Korean patient with a symptomatic pulmonary infection, is described as
      representing a novel species. Its 16S rRNA gene sequence was unique and
      phylogenetic analysis based on 16S rRNA gene sequences showed that this organism
      belonged to the Mycobacterium terrae subclade. Phenotypically, the strain was
      generally similar to M. terrae and Mycobacterium nonchromogenicum, but its growth
      rate was slower than those of other M. terrae complex strains. A unique mycolic
      acid profile and phylogenetic analysis based on two different alternative
      chronometer molecules, hsp65 and rpoB, confirm the taxonomic status of this
      strain as a representative of a novel species. The name Mycobacterium senuense
      sp. nov. is proposed, with the type strain 05-832(T) (=DSM 44999(T) =KCTC
      19147(T)).

PMID- 18319472
TI  - Virgibacillus kekensis sp. nov., a moderately halophilic bacterium isolated from
      a salt lake in China.
AB  - A Gram-positive, moderately halophilic, motile, strictly aerobic, endospore
      forming, oxidase- and catalase-positive, rod-shaped bacterium, strain YIM
      kkny16(T), was isolated from a saline mud sample collected from the Keke salt
      lake in the Qaidam Basin, north-west China. This isolate grew in the presence of
      0-25 % (w/v) NaCl and at pH 6.0-10.0 and 10-50 degrees C; optimum growth was
      observed with 10 % (w/v) NaCl and at pH 7.0 and 37 degrees C. Strain YIM
      kkny16(T) had meso-diaminopimelic acid as the diagnostic diamino acid, MK-7 as
      the predominant respiratory quinone, with a significant amount of MK-6, and
      anteiso-C(15 : 0), iso-C(14 : 0) and C(16 : 1)omega7c alcohol as major fatty
      acids. Major polar lipids were diphosphatidylglycerol and phosphatidylglycerol.
      The DNA G+C content was 41.8 mol%. Phylogenetic analysis based on 16S rRNA gene
      sequences confirmed that strain YIM kkny16(T) was a member of the genus
      Virgibacillus, exhibiting sequence similarities of 94.9-97.3 % to the type
      strains of recognized Virgibacillus species. Strain YIM kkny16(T) could be
      differentiated from recognized Virgibacillus species based on phenotypic
      characteristics, chemotaxonomic differences, phylogenetic analysis and DNA-DNA
      hybridization data. On the basis of evidence from this polyphasic study, strain
      YIM kkny16(T) is considered to represent a novel species of the genus
      Virgibacillus, for which the name Virgibacillus kekensis sp. nov. is proposed.
      The type strain is YIM kkny16(T) (=DSM 17056(T)=CGMCC 1.6298(T)).

PMID- 18319473
TI  - Microbacterium hatanonis sp. nov., isolated as a contaminant of hairspray.
AB  - An aerobic, rod-shaped, Gram-positive, oxidase-negative, catalase-positive
      bacterial isolate, strain FCC-01(T), originating as a contaminant of hairspray
      was characterized using phenotypic and molecular taxonomic methods. A 16S rRNA
      gene sequence analysis revealed that the isolate belonged to the genus
      Microbacterium and represented an evolutionary lineage that was distinct from
      recognized Microbacterium species. Cell-wall hydrolysate from the isolate
      contained ornithine and the cell-wall sugars consisted of rhamnose and galactose.
      The main respiratory quinones were MK-12 (38 %) and MK-11 (35 %). The major
      cellular fatty acids were anteiso-C(15 : 0) (48 %), anteiso-C(17 : 0) (35 %) and
      iso-C(16 : 0) (11 %). The DNA G+C content was 69 mol%. The isolate showed <98 %
      16S rRNA gene sequence similarity with respect to all of the Microbacterium
      species with validly published names. On the basis of the morphological,
      physiological and chemotaxonomic data and the results of the comparative 16S rRNA
      gene sequence analysis, this isolate represents a novel species of the genus
      Microbacterium, for which the name Microbacterium hatanonis sp. nov. is proposed.
      The type strain is FCC-01(T) (=JCM 14558(T) =DSM 19179(T)).

PMID- 18319474
TI  - Thermosulfidibacter takaii gen. nov., sp. nov., a thermophilic, hydrogen
      oxidizing, sulfur-reducing chemolithoautotroph isolated from a deep-sea
      hydrothermal field in the Southern Okinawa Trough.
AB  - A novel thermophilic, sulfur-reducing chemolithoautotroph, strain ABI70S6(T), was
      isolated from a deep-sea hydrothermal field at the Yonaguni Knoll IV, Southern
      Okinawa Trough. Cells of strain ABI70S6(T) were motile rods, 0.9-2.0 microm in
      length and 0.4-0.8 microm in width. Strain ABI70S6(T) was an obligately anaerobic
      chemolithotroph, exhibiting hydrogen oxidation coupled with sulfur reduction.
      Growth was observed at 55-78 degrees C (optimum, 70 degrees C), pH 5.0-7.5
      (optimum, pH 5.5-6.0) and 0.5-4.5 % NaCl (optimum, 3.0 % NaCl). H(2) and
      elemental sulfur were utilized as electron donor and acceptor, respectively. The
      major fatty acids were C(16 : 0) (40.0 %) and C(20 : 1) (60.0 %). The G+C content
      of genomic DNA was 44.2 mol%. The physiological attributes of strain ABI70S6(T)
      are similar to those of species of genera within the family
      Desulfurobacteriaceae, most of which are thermophilic and chemolithoautotrophic
      sulfur reducers. However, 16S rRNA gene sequence similarities between the novel
      isolate and type strains of all species within the family Desulfurobacteriaceae
      were <87 %, which is close to the similarities found between the novel isolate
      and members of the family Thermodesulfobacteriaceae (<85 %). Based on
      physiological and phylogenetic features of the novel isolate, it is proposed that
      it represents a novel species in a novel genus, Thermosulfidibacter takaii gen.
      nov., sp. nov., within the phylum Aquificae. The type strain of T. takaii is
      ABI70S6(T) (=JCM 13301(T)=DSM 17441(T)).

PMID- 18319475
TI  - Description of Caldanaerobius fijiensis gen. nov., sp. nov., an inulin-degrading,
      ethanol-producing, thermophilic bacterium from a Fijian hot spring sediment, and
      reclassification of Thermoanaerobacterium polysaccharolyticum and
      Thermoanaerobacterium zeae as Caldanaerobius polysaccharolyticus comb. nov. and
      Caldanaerobius zeae comb. nov.
AB  - An obligately anaerobic, spore-forming, Gram-type-positive but Gram-staining
      negative thermophilic bacterium, strain JW/YJL-F3(T), was isolated from a Fijian
      hot spring sediment sample. Cells of strain JW/YJL-F3(T) were straight to
      slightly curved rods, 0.5-1.2 microm in diameter and 1.5-19 microm long. The
      temperature range for growth was between 40 and 67 degrees C, with an optimum at
      60-63 degrees C. The pH(25 degrees C) range for growth was 4.5-8.4 with an
      optimum of 6.8. The salinity range for growth was 0-0.5 %. Strain JW/YJL-F3(T)
      utilized a range of substrates including arabinose, cellobiose, galactose,
      glucose, inulin, lactose, maltose, mannose, raffinose, ribose, trehalose, xylose
      and yeast extract as carbon and energy sources. The major fermentation end
      products from glucose were ethanol, acetate and formate. Strain JW/YJL-F3(T)
      converted thiosulfate to elemental sulfur, producing sulfur globules. The DNA G+C
      content was 37.6 mol% as determined by HPLC. Phylogenetic analysis using the 16S
      rRNA gene sequence indicated that the isolate is distantly related to the clade
      of the genus Thermoanaerobacterium. However, Thermoanaerobacterium
      polysaccharolyticum (96.7 % similarity to the type strain) and
      Thermoanaerobacterium zeae were the closest relatives, forming a separate, well
      supported clade together with the novel isolate. Because Thermoanaerobacterium
      polysaccharolyticum, Thermoanaerobacterium zeae and strain JW/YJL-F3(T) have
      different features from other Thermoanaerobacterium species, including a higher
      G+C content and formate production, and are placed distantly from the remaining
      species of Thermoanaerobacterium (greater than 10 % distance) in the 16S rRNA
      gene sequence analysis, we propose to place the new isolate JW/YJL-F3(T) and
      Thermoanaerobacterium polysaccharolyticum and Thermoanaerobacterium zeae into the
      novel genus Caldanaerobius gen. nov. as Caldanaerobius fijiensis gen. nov., sp.
      nov. (the type species), Caldanaerobius polysaccharolyticus comb. nov. and
      Caldanaerobius zeae comb. nov., respectively. The type strain of Caldanaerobius
      fijiensis is JW/YJL-F3(T) (=ATCC BAA-1278(T) =DSM 17918(T)).

PMID- 18319476
TI  - Bacillus velezensis is a later heterotypic synonym of Bacillus amyloliquefaciens.
AB  - Strain BCRC 14193, isolated from soil, shared more than 99 % 16S rRNA gene
      sequence similarity with Bacillus amyloliquefaciens BCRC 11601(T) and Bacillus
      velezensis BCRC 17467(T). This strain was previously identified as B.
      amyloliquefaciens, based on DNA-DNA hybridization, but its DNA relatedness value
      with B. velezensis BCRC 17467(T) was 89 %. To investigate the relatedness of
      strain BCRC 14193, B. amyloliquefaciens and B. velezensis, the partial sequence
      of the gene encoding the subunit B protein of DNA gyrase (gyrB) was determined.
      B. velezensis BCRC 17467(T) shared high gyrB gene sequence similarity with B.
      amyloliquefaciens BCRC 14193 (98.4 %) and all of the B. amyloliquefaciens strains
      available (95.5-95.6 %). DNA-DNA hybridization experiments revealed high
      relatedness values between B. velezensis BCRC 17467(T) and B. amyloliquefaciens
      BCRC 11601(T) (74 %) and the B. amyloliquefaciens reference strains (74-89 %).
      Based on these data and the lack of phenotypic distinctive characteristics, we
      propose Bacillus velezensis as a later heterotypic synonym of Bacillus
      amyloliquefaciens.

PMID- 18319477
TI  - Hydrogenivirga okinawensis sp. nov., a thermophilic sulfur-oxidizing
      chemolithoautotroph isolated from a deep-sea hydrothermal field, Southern Okinawa
      Trough.
AB  - A novel extremely thermophilic sulfur-oxidizing bacterium, strain LS12-2(T), was
      isolated from a deep-sea hydrothermal field at the Yonaguni Knoll IV, Southern
      Okinawa Trough. Cells of strain LS12-2(T) were motile rods, 1.5-4.0 microm in
      length and 0.4-0.5 microm in width. Strain LS12-2(T) was an obligate
      chemolithoautotroph that could utilize elemental sulfur or thiosulfate as an
      electron donor and nitrate or oxygen as an electron acceptor. Growth was observed
      at 65-85 degrees C (optimum 70-75 degrees C), pH 5.8-8.3 (optimum pH 6.9-7.5),
      1.0-4.0 % (w/v) NaCl (optimum 2.5 %) and 1.0-7.0 % O(2) in the gas phase (optimum
      3.0 %). Fatty acids detected were C(16 : 0) (8.0 %), C(18 : 0) (9.0 %), C(18 : 1)
      (62.5 %) and C(20 : 1) (20.5 %). The genomic DNA G+C content was 51.3 mol%. 16S
      rRNA gene sequence analysis indicated that strain LS12-2(T) belonged to the genus
      Hydrogenivirga. Based on physiological and phylogenetic characteristics of the
      isolate, it is proposed that this strain represents a novel species in the genus
      Hydrogenivirga, Hydrogenivirga okinawensis sp. nov. The type strain of
      Hydrogenivirga okinawensis is LS12-2(T) (=JCM 13302(T)=DSM 17378(T)).

PMID- 18319478
TI  - Paenibacillus provencensis sp. nov., isolated from human cerebrospinal fluid, and
      Paenibacillus urinalis sp. nov., isolated from human urine.
AB  - Gram-negative, spore-forming rods were isolated from a human urine sample (strain
      5402403(T)) and a human cerebrospinal fluid sample (strain 4401170(T)). Based on
      genotypic characteristics, these strains belonged to the genus Paenibacillus and
      were closely related. Phylogenetic analysis based on 16S rRNA gene sequence
      comparison showed that they clustered with Paenibacillus massiliensis 2301065(T)
      (95.9 and 94.3 % 16S rRNA gene sequence similarity, respectively, for strains
      5402403(T) and 4401170(T)), Paenibacillus illinoisensis NRRL NRS-61356(T) (90.6
      and 93.8 %), Paenibacillus xylanilyticus XIL14(T) (95.3 and 95.4 %),
      Paenibacillus barcinonensis BP-23(T) (94.3 and 94.0 %), Paenibacillus pabuli
      NCIMB 12781(T) (89.1 and 92.3 %) and Paenibacillus amylolyticus NRRL NRS-290(T)
      (94.2 and 93.8 %). The predominant fatty acids were 15 : 0 anteiso (49.0 and 55.3
      %, respectively, for strains 5402403(T) and 4401170(T)), 16 : 0 iso (15.4 and
      13.5 %), 16 : 0 (7.6 and 3.6 %), 15 : 0 (6.3 and 2.8 %), 17 : 0 anteiso (5.7 and
      7.5 %), 14 : 0 iso (4.1 and 2.7 %) and 15 : 0 iso (4.1 and 3.4 %). 16S rRNA gene
      sequence similarity between strain 4401170(T) and strain 5402403(T) was 98.4 %,
      but the DNA-DNA reassociation rate between the two strains was 53.2 %. So,
      considering the recommendations of the ad hoc committee, they do not belong to
      the same species. On the basis of phenotypic data and genotypic inference, it is
      proposed that the strains should be assigned to the novel species Paenibacillus
      urinalis sp. nov. (type strain 5402403(T) =CIP 109357(T) =CCUG 53521(T)) and
      Paenibacillus provencensis sp. nov. (type strain 4401170(T) =CIP 109358(T) =CCUG
      53519(T)).

PMID- 18319479
TI  - Classification of 'Streptomyces tenebrarius' Higgins and Kastner as
      Streptoalloteichus tenebrarius nom. rev., comb. nov., and emended description of
      the genus Streptoalloteichus.
AB  - Phylogenetic analysis of 'Streptomyces tenebrarius' NBRC 16177 on the basis of
      the 16S rRNA gene sequence revealed that this organism was related to
      Streptoalloteichus hindustanus. It possessed glutamic acid, alanine and meso
      diaminopimelic acid as cell-wall amino acids, galactose, mannose and glucose as
      whole-cell sugars and the menaquinones MK-10(H(6)), MK-10(H(4)), MK-9(H(6)) and
      MK-9(H(4)). The chemotaxonomic characteristics of this strain were consistent
      with those of the genus Streptoalloteichus. DNA-DNA hybridization, physiological,
      biochemical and chemotaxonomic data revealed that 'Streptomyces tenebrarius' can
      be easily differentiated from the other member of the genus Streptoalloteichus
      and that it merits separate species status. The phenotypic and genetic evidence
      reveals that 'Streptomyces tenebrarius' represents a novel species of the genus
      Streptoalloteichus; the name Streptoalloteichus tenebrarius (ex Higgins and
      Kastner) nom. rev., comb. nov. is proposed for this species. The type strain is
      NBRC 16177(T) (=ATCC 17920(T) =DSM 40477(T) =JCM 4838(T) =NRRL B-12390(T) =ISP
      5477(T)).

PMID- 18319480
TI  - Labrys portucalensis sp. nov., a fluorobenzene-degrading bacterium isolated from
      an industrially contaminated sediment in northern Portugal.
AB  - A detailed classification of a novel bacterial strain, designated F11(T), capable
      of degrading fluorobenzene as a sole carbon and energy source, was performed by
      using a polyphasic approach. This Gram-negative, rod-shaped, non-motile, non
      spore-forming, aerobic bacterium was isolated from a sediment sample collected
      from an industrially contaminated site in northern Portugal. The predominant
      whole-cell fatty acids were C(19 : 0) cyclo omega8c, C(16 : 0), C(18 : 1)omega7c,
      C(18 : 0), C(18 : 0) 3-OH and C(16 : 0) 3-OH. The G+C content of the DNA was 62.9
      mol% and the major respiratory quinone was ubiquinone 10 (UQ-10). 16S rRNA gene
      sequence analysis revealed that strain F11(T) was a member of the class
      Alphaproteobacteria and was phylogenetically related to the genus Labrys, having
      sequence similarities of 95.6 and 93.1 % to the type strains of Labrys monachus
      and Labrys methylaminiphilus, respectively. DNA-DNA hybridization experiments
      revealed levels of relatedness of <70 % between strain F11(T) and the type
      strains of L. monachus and L. methylaminiphilus (38.6 and 34.1 %, respectively),
      justifying the classification of strain F11(T) as representing a novel species of
      the genus Labrys. The name Labrys portucalensis sp. nov. is proposed for this
      organism. The type strain is F11(T) (=LMG 23412(T)=DSM 17916(T)).

PMID- 18319481
TI  - Nocardiopsis quinghaiensis sp. nov., isolated from saline soil in China.
AB  - A previously unknown Gram-positive, obligately aerobic actinomycete, YIM 28A4(T),
      was isolated from a sample of saline soil collected from the Qaidam Basin in
      Qinghai Province, north-west China, and was investigated using a polyphasic
      taxonomic approach. The strain grew well on most of the media tested, producing
      white to pale-yellow substrate mycelium, white aerial mycelium and straight to
      flexuous hyphae. The substrate mycelium was well developed and fragmented with
      age; the aerial mycelium produced long, straight spore chains. The spore chains
      were composed of non-motile, smooth-surfaced, rod-shaped spores. No diffusible
      pigments were produced on any of the media tested. The strain grew in the
      presence of 0-10 % (w/v) NaCl and at pH 6.0-8.0, with optimum growth occurring at
      3 % (w/v) NaCl and pH 7.0. It grew at 10-37 degrees C, the optimum growth
      temperature being 28 degrees C. Whole-cell hydrolysates of strain YIM 28A4(T)
      contained meso-diaminopimelic acid and no diagnostic sugars. The predominant
      phospholipids were phosphatidylcholine, phosphatidylglycerol and
      diphosphatidylglycerol. The predominant menaquinones were MK-10, MK-10(H(2)), MK
      11 and MK-11(H(2)). The major cellular fatty acids were iso-C(16 : 0), anteiso
      C(15 : 0) and anteiso-C(17 : 0). The DNA G+C content was 67.1 mol%. The
      morphological and chemotaxonomic characteristics of the isolate matched those
      described for Nocardiopsis species. A phylogenetic analysis based on 16S rRNA
      gene sequence comparisons confirmed that strain YIM 28A4(T) was a member of the
      genus Nocardiopsis and most closely related to the type strains Nocardiopsis
      aegyptia DSM 44442(T) and Nocardiopsis halotolerans DSM 44410(T), showing 98.1
      and 97.8 % 16S rRNA gene sequence similarity, respectively. Strain YIM 28A4(T)
      can be differentiated from these type strains by using phenotypic, phylogenetic
      and DNA-DNA hybridization data. On the basis of the polyphasic evidence, strain
      YIM 28A4(T) represents a novel species of the genus Nocardiopsis, for which the
      name Nocardiopsis quinghaiensis sp. nov. is proposed. The type strain is YIM
      28A4(T) (=DSM 44739(T) =CGMCC 4.3494(T)).

PMID- 18319482
TI  - Pseudomonas marincola sp. nov., isolated from marine environments.
AB  - An aerobic, Gram-negative, motile, non-pigmented bacterium, strain KMM 3042(T),
      isolated from a deep-sea brittle star in the Fiji Sea, was subjected to a
      polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene
      sequences revealed marine Mn(II)-oxidizing isolate S185-2B as the closest
      neighbour of strain KMM 3042(T) (99.9 % sequence similarity). The two strains
      formed a distinct lineage within the genus Pseudomonas adjacent to the members of
      the Pseudomonas borbori cluster, sharing highest sequence similarity of 97.4 and
      97.0 %, respectively, with P. borbori DSM 17834(T) and Pseudomonas flavescens DSM
      12071(T). The DNA-DNA hybridization value (71 %) between strains KMM 3042(T) and
      S185-2B confirmed their assignment to the same species. On the basis of
      phylogenetic analysis, DNA-DNA hybridization and physiological and biochemical
      characterization, strains KMM 3042(T) and S185-2B should be assigned to a novel
      species of the genus Pseudomonas, for which the name Pseudomonas marincola sp.
      nov. is proposed. The type strain is KMM 3042(T) (=NRIC 0729(T) =JCM 14761(T)).

PMID- 18319483
TI  - Thalassospira tepidiphila sp. nov., a polycyclic aromatic hydrocarbon-degrading
      bacterium isolated from seawater.
AB  - A Gram-negative, mesophilic bacterial strain, designated 1-1B(T), which degrades
      polycyclic aromatic hydrocarbons, was isolated from petroleum-contaminated
      seawater during a bioremediation experiment. A 16S rRNA gene sequence analysis
      indicated that the isolate was affiliated with the genus Thalassospira in the
      Alphaproteobacteria; the sequence was found to be most similar to those of
      Thalassospira profundimaris WP0211(T) (99.8 %), Thalassospira xiamenensis M-5(T)
      (98.2 %) and Thalassospira lucentensis DSM 14000(T) (98.1 %). However, the levels
      of DNA-DNA relatedness between strain 1-1B(T) and these type strains were 50.7+/
      17.2, 35.7+/-17.8 and 32.0+/-21.1 %, respectively. In addition, strain 1-1B(T)
      was found to be distinct from the other described species of the genus
      Thalassospira in terms of some taxonomically important traits, including DNA G+C
      content, optimum growth temperature, salinity tolerance, utilization of carbon
      sources and fatty acid composition. Furthermore, strain 1-1B(T) and T.
      profundimaris were also different with regard to motility and denitrification
      capacities. On the basis of physiological and DNA-DNA hybridization data, strain
      1-1B(T) represents a novel species within the genus Thalassospira, for which the
      name Thalassospira tepidiphila sp. nov. is proposed. The type strain is 1-1B(T)
      (=JCM 14578(T) =DSM 18888(T)).

PMID- 18319484
TI  - Multigene phylogenies of clonal Spumella-like strains, a cryptic heterotrophic
      nanoflagellate, isolated from different geographical regions.
AB  - Many nanoflagellate morphospecies comprise an enormous variation of genotypes,
      probably indicating cryptic species. One of the best-investigated morphospecies
      with respect to molecular and ecophysiological variation are flagellates of the
      Spumella morphotype. Here, we have phylogenetically analysed three protein-coding
      genes (actin, alpha-tubulin, beta-tubulin), internal transcribed spacers (ITS1,
      ITS2) and the 5.8S rDNA of 17 Spumella-like strains isolated from soil,
      freshwater and marine samples in order to (i) test the validity of the current
      Spumella-like phylogenetic classification system based exclusively on small
      subunit (SSU) rDNA, (ii) elucidate the phylogenetic associations of SSU rDNA
      unresolved strains and (iii) evaluate the validity of the assignment of
      ecophysiological adaptations to previously identified SSU rDNA sequence clades.
      All single-gene analyses show different patterns of support, are incongruent and
      identify a number of conflicting nodes. Likewise, a concatenation of all protein
      genes fails to recover specific SSU rDNA clades. However, a combined analysis of
      all genes confidently resolved the conflicts of the single genes and the protein
      gene concatenations and resulted in a tree topology that is identical to the SSU
      rDNA analysis, but with enhanced phylogenetic resolution and decisively greater
      support. We conclude that, depending on the genes concatenated, a 'supergene'
      analysis minimizes artefactual effects of single genes and may be superior in its
      performance in phylogenetically analysing cryptic species. We confirm the
      validity of the SSU rDNA Spumella-like phyloclades and support the suggestion
      that these clades indeed seem to reflect certain ecophysiological adaptations.

PMID- 18319485
TI  - Two novel aflatoxin-producing Aspergillus species from Argentinean peanuts.
AB  - Two novel species from Aspergillus section Flavi from different species of
      Arachis (peanuts) in Argentina are described as Aspergillus arachidicola sp. nov.
      and Aspergillus minisclerotigenes sp. nov. Their novel taxonomic status was
      determined using a polyphasic taxonomic approach with phenotypic (morphology and
      extrolite profiles) and molecular (beta-tubulin and calmodulin gene sequences)
      characters. A. minisclerotigenes resembles Aspergillus flavus and Aspergillus
      parvisclerotigenus in producing aflatoxins B(1) and B(2), cyclopiazonic acid,
      kojic acid and aspergillic acid, but in addition it produces aflatoxins G(1) and
      G(2), aflavarins, aflatrem, aflavinines, parasiticolides and paspaline. This
      species also includes several isolates previously assigned to A. flavus group II
      and three Australian soil isolates. A. arachidicola produces aflatoxins B(1),
      B(2), G(1) and G(2), kojic acid, chrysogine and parasiticolide, and some strains
      produce aspergillic acid. The type strain of A. arachidicola is CBS 117610(T)
      =IBT 25020(T) and that of A. minisclerotigenes is CBS 117635(T) =IBT 27196(T).
      The Mycobank accession numbers for Aspergillus minisclerotigenes sp. nov. and
      Aspergillus arachidicola sp. nov. are respectively MB 505188 and MB 505189
      (http://www.mycobank.org).

PMID- 18319486
TI  - Reappraisal of the Sporobolomyces roseus species complex and description of
      Sporidiobolus metaroseus sp. nov.
AB  - Here, we investigate a group of red to pinkish ballistoconidia-forming yeasts
      that were preliminarily identified as Sporobolomyces roseus or Sporidiobolus
      pararoseus. Detailed molecular and micromorphological studies revealed that the
      sexual strains and several conspecific anamorphic isolates belonged to a novel
      teleomorph that represents the sexual stage of Sporobolomyces roseus.
      Consequently, a new taxon in the genus Sporidiobolus is here described as
      Sporidiobolus metaroseus sp. nov. (type strain CBS 7683(T)). The main
      characteristics of Sporidiobolus metaroseus are presented and compared with those
      of the more closely related species. Our studies also led to the clarification of
      the life cycle of Sporidiobolus pararoseus. We confirm that the teliospores of
      this species germinate by forming short branches of hyphae, instead of basidia.

PMID- 18319487
TI  - Proposal to replace the illegitimate genus name Bryantella Wolin et al. 2004VP
      with the genus name Marvinbryantia gen. nov. and to replace the illegitimate
      combination Bryantella formatexigens Wolin et al. 2004VP with Marvinbryantia
      formatexigens comb. nov.
AB  - The prokaryote generic name Bryantella Wolin et al. 2004(VP) is illegitimate
      because it is a later homonym of Bryantella Chickering, 1946 (Animalia,
      Arthropoda, Arachnida, Araneae, Salticidae, Dendryphantinae, Dendryphantini) and
      a later homonym of Bryantella Britton, 1957 (Animalia, Arthropoda, Scarabaeoidea,
      Scarabaeidae, Melolonthinae) [Principle 2, Rule 51b(4) of the Bacteriological
      Code (1990 Revision)]. Bryantella represents a genus of jumping spiders within
      the family Salticidae and a genus of melolonthine scarab beetles within the
      family Scarabaeidae. Therefore, a new genus name, Marvinbryantia gen. nov., is
      proposed for this taxon. As a result, a new combination, Marvinbryantia
      formatexigens comb. nov., is required for the type species to replace the
      illegitimate combination Bryantella formatexigens Wolin et al. 2004(VP).

PMID- 18319488
TI  - Diabetes specialists keep ACCORD data in perspective.

PMID- 18319489
TI  - State-paid medication therapy management services succeed.

PMID- 18319490
TI  - EPA inspections of drug disposal practices can be a learning moment.

PMID- 18319491
TI  - Palliative care pharmacists consider patients' psychosocial issues.

PMID- 18319493
TI  - Indocyanine green availability from compounding pharmacies.

PMID- 18319494
TI  - Unintentional overdose of insulin glargine.

PMID- 18319495
TI  - Development and maintenance of an online formulary for a large health system.

PMID- 18319496
TI  - Using self-talk to enhance career satisfaction and performance.

PMID- 18319497
TI  - Sitagliptin: a novel agent for the management of type 2 diabetes mellitus.
AB  - PURPOSE: The pharmacologic, pharmacokinetic, safety, clinical efficacy, and role
      of sitagliptin in the management of type 2 diabetes mellitus are reviewed.
      SUMMARY: Sitagliptin is a dipeptidyl-peptidase IV (DPP4) inhibitor that increases
      insulin release and decreases glucagon levels by preventing the activation of
      incretin hormones--glucagon-like peptide-1 and glucose-dependent insulinotropic
      polypeptide. The clinical trials reviewed provide evidence that sitagliptin,
      either alone or in combination with metformin or thiazolidinediones, is effective
      in reducing glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, and two
      hour postprandial glucose levels in patients with type 2 diabetes. Specifically,
      sitagliptin has a role in patients who have been compliant with their oral
      hypoglycemic agents but unable to attain target HbA(1c) values with monotherapy
      and lifestyle modifications. Sitagliptin is generally well tolerated, with the
      frequency of adverse events being similar to placebo and a low frequency of
      hypoglycemia. Sitagliptin does not appear to alter the pharmacokinetics of
      metformin, rosiglitazone, glyburide, simvastatin, warfarin, or oral
      contraceptives. The addition of sitagliptin to a patient's oral antidiabetic
      regimen would necessitate close monitoring for adverse events and possible drug
      interactions. The sitagliptin dosage recommended by the manufacturer is 100 mg
      once daily as monotherapy or in combination with metformin or a
      thiazolidinedione. No formal pharmacoeconomic evaluations of sitagliptin therapy
      have been conducted. CONCLUSION: Sitagliptin, a DPP4 inhibitor, offers a novel
      treatment option for patients with type 2 diabetes mellitus.

PMID- 18319498
TI  - Teriparatide in the treatment of osteoporosis.
AB  - PURPOSE: The efficacy, safety, and cost of teriparatide in the treatment of
      osteoporosis are reviewed. SUMMARY: Osteoporosis is a leading cause of fractures
      in women and men but is underdiagnosed and undertreated. Antiresorptive therapies
      (calcitonin, estrogen, bisphosphonates, and selective estrogen-receptor
      modulators) have historically been used to treat this condition. Teriparatide
      (recombinant human parathyroid hormone) is an anabolic agent labeled for use in
      postmenopausal women and men with osteoporosis who are at high risk for
      fractures. Clinical trials indicate that teriparatide increases predominantly
      trabecular bone in the lumbar spine and femoral neck; it has less significant
      effects at cortical sites. The combination of teriparatide with antiresorptive
      agents is not more effective than teriparatide monotherapy. The most common
      adverse effects associated with teriparatide include injection-site pain, nausea,
      headaches, leg cramps, and dizziness. After a maximum of two years of
      teriparatide therapy, the drug should be discontinued and antiresorptive therapy
      begun to maintain bone mineral density. Teriparatide is expensive but may be cost
      effective in selected patients. CONCLUSION: Teriparatide offers a therapeutic
      option for patients at high risk of an osteoporotic fracture and for patients who
      are intolerant of or unresponsive to antiresorptive therapy.

PMID- 18319499
TI  - Erythropoietic agents for anemia of critical illness.
AB  - PURPOSE: Evidence regarding the cost-effective use of and benefits associated
      with epoetin alfa in treating anemia of critically ill patients is assessed.
      SUMMARY: Anemia of critical illness is a leading cause of inadequate oxygen
      delivery that affects almost all patients in the intensive care unit setting
      after day 3. Red blood cell transfusions are commonly used to correct anemia of
      critical illness, but they are also associated with risks including hemolytic
      reactions and viral transmission. The latest evidence suggests that when a strict
      transfusion protocol is implemented, epoetin alfa does not decrease the
      transfusion requirements of critically ill patients. In the absence of a strict
      transfusion protocol, an average of 5.1 doses of epoetin, at a cost of $2154, is
      required to avoid one transfusion. Evidence is accumulating that epoetin may
      reduce mortality rates in trauma patients. However, important questions remain
      regarding the magnitude and mechanism of the potential benefit and if the benefit
      outweighs the risk of thromboembolism. Therefore, the reduction in transfusion
      related adverse events is the only clinical outcome benefit that is well
      supported by current evidence. However, the known risk of transfusion-related
      adverse events is low; approximately 29,000 patients would need to be treated to
      avoid a serious transfusion-related event. Treating these patients would cost
      over $25 million, and it would take over 100 years to prevent one serious event
      in a unit admitting 20 epoetin-eligible patients per month. CONCLUSION: Published
      data suggest a prohibitive cost associated with epoetin alfa use in critically
      ill patients given that the only well-supported clinical benefit of this
      treatment is the avoidance of transfusion-related adverse events. Continued
      research is necessary to clarify if there is a net clinical benefit of epoetin
      use (especially in trauma patients) and to develop optimal blood management
      strategies.

PMID- 18319500
TI  - Ciprofloxacin-induced Q-T interval prolongation.
AB  - PURPOSE: A case of Q-T interval prolongation in a pediatric patient with no known
      risk factors for the development of a long Q-T syndrome is reported. SUMMARY: A
      16-year-old boy arrived at a children's hospital reporting mucous diarrhea that
      had lasted two weeks, light-headedness with two blackouts on the day before his
      arrival to the hospital, and a 4.3-kg weight loss over the previous three weeks.
      He had a 3.5-year history of Crohn's disease and had been hospitalized for two
      months with a diagnosis of colitis with cryptitis. He was admitted for the
      treatment of an acute flare of Crohn's disease and a perirectal abscess. The
      patient was started on i.v. ciprofloxacin 400 mg twice daily and metronidazole
      500 mg every six hours. The selected agents provided adequate empirical coverage
      of the suspected organisms and would not be contraindicated with the patient's
      allergy to penicillin. Within 48 hours of administration of ciprofloxacin, the
      patient became bradycardic. The cardiology service was consulted, and an
      electrocardiogram showed a mildly prolonged Q-T interval (corrected Q-T interval,
      486 msec) and low heart rate (42 beats/min). Antimicrobial therapy was changed to
      ampicillin and then to linezolid. The patient's Q-T interval normalized within
      seven days of ciprofloxacin discontinuation. The patient had no further cardiac
      anomalies. Two weeks later, he was discharged on linezolid and aztreonam for the
      treatment of his abscess and was responding to treatment. CONCLUSION: A pediatric
      patient with Crohn's disease and colitis with cryptitis developed a prolonged Q-T
      interval within 48 hours of treatment with ciprofloxacin.

PMID- 18319501
TI  - Undocumented source of pharmacy benefit manager revenue.
AB  - PURPOSE: The difference between what pharmacy benefit management companies (PBMs)
      charge prescription benefit plan sponsors and what dispensing pharmacies are paid
      ("spread") was studied. METHODS: Data from prescription transaction invoices from
      two large employer groups, each using a different PBM, and 84 community
      pharmacies (which differed for each employer group due to clear geographic
      separation) participating in these plans between October 1, 2002, and December
      31, 2004, were studied. Detailed community pharmacy payment transaction records
      were compared with PBM claim records from two employers. One employer provided
      49,633 prescription claim records, and the other employer provided 120,684
      prescription claim records. Spread between amount due billed to the employer by
      the PBM and amount due paid to the dispensing pharmacy by the PBM for all
      prescriptions, for brand-name prescriptions, and for generic prescriptions was
      analyzed. RESULTS: For the two PBMs combined, the mean +/- S.D. spread for 20,376
      paid transactions was $1.82 +/- $8.26 per prescription. The mean +/- S.D. spread
      for brand-name prescriptions was $0.07 +/- $5.18 and for generic medications was
      $4.20 +/- $10.69 per prescription. The two PBMs differed significantly in their
      spread for all drugs ($2.30 +/- $6.17 and $1.78 +/- $8.40) and for brand-name
      drugs ($0.47 +/- $3.21 and $0.04 +/- $5.30). The difference between PBMs for
      spreads on generic medications did not achieve statistical significance.
      CONCLUSION: Wide variations in spread pricing existed between two PBMs and
      between brand-name and generic medications. Pharmacists and prescription benefit
      plan sponsors should be aware of this discrepancy and seek a more transparent
      contract with PBMs.

PMID- 18319502
TI  - Stability of a flavored formulation of acetylcysteine for oral administration.
AB  - PURPOSE: The chemical and physical stability of a flavored solution of
      acetylcysteine stored at room temperature or under refrigeration for up to 35
      days in amber plastic prescription bottles were studied. METHODS: The flavored
      acetylcysteine solution was prepared by adding a sweetener and a strawberry
      creamsicle flavoring to acetylcysteine solution 10% to a final nominal
      acetylcysteine concentration of 86.5 mg/mL. Six identical samples of the
      formulation were prepared in amber plastic prescription bottles. Three bottles
      were stored at room temperature (23-25 degrees C) and the other three were stored
      in the refrigerator (3-5 degrees C). Immediately after preparation and at 7, 14,
      21, 28, and 35 days, each sample was assayed in duplicate by high- performance
      liquid chromatography. Stability was defined as the retention of at least 90% of
      the initial drug concentration. RESULTS: On day 35, the refrigerated
      acetylcysteine samples retained 96.7% of their initial concentration. The samples
      stored at room temperature retained 92.5% of their initial concentration.
      CONCLUSION: A flavored oral formulation of acetylcysteine 86.5 mg/mL was stable
      for at least 35 days when stored at room temperature and in the refrigerator in
      amber plastic bottles.

PMID- 18319503
TI  - Dietary supplement use in pediatric patients with cystic fibrosis.
AB  - PURPOSE: The use of dietary supplements and their perceived effectiveness in
      pediatric patients with cystic fibrosis (CF) were studied. METHODS: A descriptive
      survey, comprising both open- and closed-ended questions, was developed to assess
      current and past use of dietary supplements, identify sources of dietary
      supplement information, determine the perceived effectiveness of these dietary
      supplements, and evaluate families' knowledge of regulations regarding dietary
      supplements. RESULTS: A total of 121 pediatric CF patients and their families
      completed the survey. Assessment of dietary supplement use showed that 19% of
      patients (n = 23) were currently using dietary supplements and 10% (n = 12)
      reported past dietary supplement use. A total of 5 patients reported both current
      and past use of dietary supplements. Almost 40% of the patients who reported
      dietary supplement use did not inform their primary care provider about their
      use. While many factors may influence a patient's decision to begin therapy with
      a dietary supplement, 20% (n = 6) of patients felt their physician was most
      influential. Most patients (n = 104, 86%) correctly believed that dietary
      supplements are not regulated in the same manner as other prescription
      medications; however, only 60% (n = 72) would change the way dietary supplements
      are regulated. CONCLUSION: The use of dietary supplements in pediatric patients
      with CF was common, although few patients and families perceived it as effective
      for treating CF.

PMID- 18319504
TI  - Enhancing clinical services by using pharmacy students during advanced
      experiential rotations.

PMID- 18319505
TI  - Medication order communication using fax and document-imaging technologies.
AB  - PURPOSE: The implementation of fax and document-imaging technology to
      electronically communicate medication orders from nursing stations to the
      pharmacy is described. METHODS: The evaluation of a commercially available
      pharmacy order imaging system to improve order communication and to make document
      retrieval more efficient led to the selection and customization of a system
      already licensed and used in seven affiliated hospitals. The system consisted of
      existing fax machines and document-imaging software that would capture images of
      written orders and send them from nursing stations to a central database server.
      Pharmacists would then retrieve the images and enter the orders in an electronic
      medical record system. The pharmacy representatives from all seven hospitals
      agreed on the configuration and functionality of the custom application. RESULTS:
      A 30-day trial of the order imaging system was successfully conducted at one of
      the larger institutions. The new system was then implemented at the remaining six
      hospitals over a period of 60 days. The transition from a paper-order system to
      electronic communication via a standardized pharmacy document management
      application tailored to the specific needs of this health system was
      accomplished. CONCLUSION: A health system with seven affiliated hospitals
      successfully implemented electronic communication and the management of inpatient
      paper-chart orders by using faxes and document-imaging technology. This
      standardized application eliminated the problems associated with the hand
      delivery of paper orders, the use of the pneumatic tube system, and the printing
      of traditional faxes.

PMID- 18319507
TI  - Do decision biases predict bad decisions? Omission bias, naturalness bias, and
      influenza vaccination.
AB  - PURPOSE: Numerous studies using hypothetical vignettes have demonstrated decision
      biases or deviations from utility theory. Do people who commit biases in
      questionnaire studies make worse real-world decisions than do less biased people?
      METHODS: Two hundred seventy university faculty and staff participated in a
      questionnaire study in which they reported whether they accepted a free influenza
      vaccine offered at their work place. Influenza vaccine acceptance was the measure
      of real-world decision making. Participants responded to 3 hypothetical
      scenarios. Two scenarios measured the omission bias and described a vaccine
      (scenario 1) and a medication (scenario 2) that prevented a negative health
      outcome but that itself could cause the negative health outcome. The omission
      bias is a preference for not vaccinating or medicating even when the
      vaccine/medication lowers the total risk of the negative outcome. A 3rd scenario
      measured the naturalness bias by presenting a choice between 2 chemically
      identical medications, one extracted from a natural herb and the other
      synthesized in a laboratory. Preference for the natural medication indicated the
      naturalness bias. RESULTS: The results indicated that a substantial proportion of
      participants exhibited these biases and that participants who exhibited these
      biases were less likely to accept the flu vaccine. CONCLUSIONS: To the extent
      that declining a free flu vaccine is a worse real-world decision, people who
      demonstrate the naturalness and omission biases in hypothetical scenarios make
      worse real-world decisions.

PMID- 18319508
TI  - Impact of PSA screening on the incidence of advanced stage prostate cancer in the
      United States: a surveillance modeling approach.
AB  - BACKGROUND: and objective. Both the detection and the treatment of prostate
      cancer have undergone important clinical advances. Simultaneously, both distant
      stage incidence and disease-specific mortality have fallen in the United States.
      A recent study suggests that if prostate-specific antigen (PSA) testing explains
      the decline in distant stage incidence, then it may be largely responsible for
      the decline in mortality. The objective was to quantify this link between PSA
      screening and the decline in distant stage incidence. METHODS: A fixed-cohort
      simulation model of prostate cancer progression and screening was adapted to a
      population-based model that integrates new data on trends in testing and biopsy
      practices. The model was calibrated to pre-PSA incidence and then screening was
      superimposed, obtaining incidence projections in the absence and presence of
      testing. This approach permits calculation of clinically relevant measures for
      model validation and direct assessment of the role of testing in the distant
      stage incidence decline. RESULTS: The model validated well with prior studies of
      natural history, and the sensitivity analysis indicated that the findings were
      robust to variation in model parameters. Model results indicate that PSA
      screening accounts for approximately 80% of the observed decline in distant stage
      incidence. CONCLUSIONS: PSA screening contributed to the observed declines in
      distant stage incidence and mortality in the 1990s. However, additional factors,
      such as increasing awareness of prostate cancer and advances in treatment, have
      probably also played a role in these trends.

PMID- 18319510
TI  - Psychosocial impact of poverty on antiretroviral nonadherence among HIV-TB
      coinfected patients in Lima, Peru.
AB  - OBJECTIVE: Tuberculosis and HIV coinfection poses unique clinical and
      psychosocial complexities that can impact nonadherence to highly active
      antiretroviral treatment (HAART). METHODS: This was a prospective case series to
      identify risk factors for HAART nonadherence among 43 patients with HIV and
      tuberculosis (TB) in Lima, Peru. Nonadherence was defined by patient self-report.
      RESULTS: The median initial CD4 and HIV viral load were 63 and 159,000,
      respectively. Patients had received a median of 6.1 months of ART. Univariable
      analysis found low social support, substance use, and depression to be associated
      with nonadherence. In multivariable analysis, low social support was associated
      with nonadherence. CONCLUSIONS: In the authors' urban cohort of HIV-TB coinfected
      individuals in Lima, Peru, substance use, depression, and lack of social support
      were key barriers to adherence. These findings suggest that adherence
      interventions may be unsuccessful unless they target the underlying psychosocial
      challenges faced by patients living with TB and AIDS.

PMID- 18319511
TI  - Clinical presentations of newly diagnosed HIV-infected patients at a university
      hospital in Bangkok, Thailand.
AB  - BACKGROUND: Epidemiology and clinical features of newly diagnosed HIV-infected
      patients vary and depend on period of time and geographical area. METHODS: A
      retrospective review was conducted in adults with positive HIV antibody testing
      between January and December 2006 at a university hospital setting. RESULTS:
      Prevalence of HIV infection was 1.0%. There were 221 patients with a median age
      of 35.5 (range, 15.8-72.3) years, and 57% were males. The most common risk of HIV
      acquisition was heterosexual (63.8%). The most common reason for HIV testing was
      preoperative screening (41.2%). Of all, 52.9%, 37.1%, and 10% were diagnosed as
      AIDS, asymptomatic, and symptomatic patients, respectively. Median CD4 count at
      HIV diagnosis was 260 (range, 6-1284) cells/mm(3). AIDS-defining illnesses were
      found in 35.7%. Overall mortality rate was 1.8%. CONCLUSIONS: More than half of
      newly diagnosed HIV-infected patients have advanced HIV disease and are unaware
      of their HIV status. These results reflect inadequate education of HIV risks and
      voluntary HIV testing in Thailand.

PMID- 18319512
TI  - Racial variance in rationale for HIV testing in community-based setting in the
      United States: evidence from the National Health Interview Survey.
AB  - BACKGROUND: HIV testing varies across racial/ethnic groups in the United States,
      but it is unclear whether the rationale for testing differs as well racially. The
      authors aimed to assess the rationale for HIV testing and the racial/ethnic
      variation therein. METHODS: Using the National Health Interview Survey 2003 (n =
      29 753), the authors examined the association between rationale for HIV testing
      and race. Chi-square statistic and multinomial logistic regression analyses were
      used to test for racial differences and the effect of race/ethnicity on the
      rationale for HIV testing. RESULTS: There was a statistically significant racial
      difference with respect to HIV testing rationale, chi(2) = (24, N = 10,481) =
      808.9, P < .001. After adjustment for relevant covariates, compared with
      Caucasians, African Americans were 37% less likely to be tested due to exposure
      to sex/drugs, whereas Hispanics were not (prevalence risk ratio [PRR], 0.63, 95%
      confidence interval [CI] = 0.47-0.84, respectively). Likewise African Americans
      and Hispanics were less likely to be tested if they were sick or had a medical
      problem (PRR = 0.66, 95% CI = 0.44-0.99 and PRR = 0.65, 95% CI = 0.43-0.98).
      CONCLUSIONS: Substantial racial variation occurred in the reasons for being
      tested for HIV in the United States, indicative of the need to understand such
      rationale for effective HIV screening and testing.

PMID- 18319513
TI  - Possible case of CNS Whipple's disease in an adolescent with AIDS.
AB  - An adolescent with HIV/AIDS presented subacutely with progressive encephalopathy,
      spastic quadraplegia, and diarrhea. His brain biopsy was suggestive of central
      nervous system Whipple's disease, a disease rarely described in HIV patients. Due
      to overlapping, nonspecific symptoms associated with several opportunistic
      infections and to the difficulty in culturing the causative organism Tropheryma
      whipplei, Whipple's disease may be more common than previously suspected, and it
      is an important consideration in patients with AIDS.

PMID- 18319516
TI  - Motivating people to move: exercise behavior research.

PMID- 18319518
TI  - Sixty-four multislice computed tomography after transcutaneous implantation of a
      Cribier-Edwards bioprosthesis in the aortic position.

PMID- 18319519
TI  - Adverse outcomes in fibrinolytic-based facilitated percutaneous coronary
      intervention: insights from the ASSENT-4 PCI electrocardiographic substudy.
AB  - AIMS: Patients in ASSENT-4 PCI undergoing tenecteplase-facilitated percutaneous
      coronary intervention (PCI) had more adverse events than those undergoing primary
      PCI. We analysed this to gain further insights. METHODS AND RESULTS: A total of
      549 patients with facilitated PCI and 541 undergoing primary PCI were
      characterized according to the extent of ST resolution. We also examined the
      relationship between time from symptom onset, presence of baseline Q waves, and
      90 day events. Irrespective of treatment, 90 day mortality was lowest among 186
      patients with complete ST resolution at both 60 and 180 min (1.8% facilitated; 0%
      primary PCI group) and highest in those 502 patients without complete ST
      resolution at either 60 or 180 min (6.7% facilitated; 5.2% primary PCI group, all
      P < or = 0.05). Patients undergoing facilitated PCI presenting >3 h with baseline
      Q waves also had higher 90 day mortality compared with those without Q waves
      (10.4 vs. 2.5%, P = 0.056). No significant differences were found within primary
      PCI patients on the basis of time from symptom onset or presence of initial Q
      waves. CONCLUSION: In this post hoc analysis, our data suggest that a
      fibrinolysis-facilitated PCI strategy was especially harmful in patients
      presenting beyond 3 h from symptom onset with established Q waves on their
      baseline ECG. This may relate to the convergence of later, less effective pre
      procedural reperfusion but persisting exposure to the pro-thrombotic and bleeding
      risks of fibrinolysis.

PMID- 18319520
TI  - A simple method to irradiate blood cells in vitro with radon gas.
AB  - The design and dosimetry of a novel in vitro radon irradiation facility to
      investigate cytogenetic damage induced by radon and progeny is described. The
      system offers a 4pi geometry for uniform irradiation, proving a versatile and
      convenient facility for irradiation of whole blood cells in suspension or media.
      Doses can be controlled as exact volumes of the gas can be dispensed and measured
      by the Lucas cell. Irradiation of blood samples could be carried out in a unique
      and safe manner and the present study is an attempt to demonstrate the usefulness
      of a facility to expose blood lymphocytes in vitro to radon and its decay
      products for chromosome aberration analysis. The preliminary results obtained
      using this facility are presented. Results show an increase in dicentric
      frequency with increasing concentration of radon (r = 0.97, P < 0.0001). Multiple
      aberrations in a single cell, characteristic of high linear energy transfer
      radiation, confirm the effect of alpha exposure.

PMID- 18319521
TI  - Recent progress in allergen immunotherapy.
AB  - The efficacy of allergen immunotherapy for the treatment of allergic
      rhinoconjunctivitis with or without seasonal bronchial asthma and anaphylaxis
      caused by the sting of the hymenoptera class of insects has been clearly
      demonstrated in numerous well-designed, placebo-controlled trials. Immunotherapy
      whether by subcutaneous injection of allergen extract or by oral/sublingual
      routes modifies peripheral and mucosal TH2 responses in favour of TH1 responses
      and augments IL-10 synthesis by TRegs both locally and by peripheral T cells.
      Recent researches into the cellular and molecular basis of allergic reactions
      have advanced our understanding of the mechanisms involved in allergic diseases.
      They have also helped the development of innovative approaches that are likely to
      further improve the control of allergic responses in the future. Novel approaches
      to immunotherapy that are currently being explored include the use of peptide
      based allergen preparations, which do not bind IgE and therefore do not activate
      mast cells, but reduce both Th1 and Th2-cytokine synthesis, while increasing
      levels of IL-10. Alternative strategies include the use of adjuvants, such as
      nucleotide immunostimulatory sequences derived from bacteria CpG or
      monophosphoryl lipid A that potentiate Th1 responses. Blocking the effects of IgE
      using anti-IgE such as omalizumab, a recombinant humanized monoclonal antibody
      that selectively binds to IgE, has been shown to be a useful strategy in the
      treatment of allergic asthma and rhinitis. The combination of anti-IgE-monoclonal
      antibody omalizumab with allergen immunotherapy has proved beneficial for the
      treatment of allergic diseases, offering improved efficacy, limited adverse
      effects, and potential immune-modifying effects. This combination may also
      accelerate the rapidity by which immunotherapy induces TReg cells. If allergic
      diseases are due to a lack of allergen-specific TReg cells, then effective
      therapies should target the induction and the development of TReg cells producing
      cytokines such as IL-10.

PMID- 18319522
TI  - Immunophenotypic characterization of the leukemic B-cells from Iranian patients
      with chronic lymphocytic leukemia: association between CD38 expression and
      disease progression.
AB  - BACKGROUND: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have
      heterogeneous clinical courses, thus several biological parameters need to be
      added to the current clinical staging systems to predict disease outcome. Recent
      immunophenotypic studies performed mainly in Western populations have
      demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL.
      OBJECTIVES: To investigate the expression pattern of a variety of membrane
      antigens on leukemic cells from Iranian patients with CLL and to find out if
      there are any differences in the expression of these markers between indolent and
      progressive groups. METHODS: In the present study, peripheral blood samples from
      87 Iranian patients with B-CLL were analysed by flow cytometry. RESULTS: In all
      cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast
      majority of the cases expressed CD23, but failed to stain for CD3 or CD14. The
      leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87,
      83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the
      indolent (n=42) and progressive (n=37) patients revealed significantly higher
      frequency and intensity of CD38 expression in progressive group (40.5%) compared
      to indolent (11.9%) patients (p<0.05). None of the other membrane antigens were
      differentially expressed in these two groups of patients. CONCLUSION: Our results
      obtained in an Asian ethnic population confirm and extend previous findings
      obtained from Western populations regarding the association of CD38 expression
      and disease progression in B-CLL.

PMID- 18319523
TI  - Listeria monocytogenes activated dendritic cell based vaccine for prevention of
      experimental tumor in mice.
AB  - BACKGROUND: The use of dendritic cells (DCs) as a cellular adjuvant provides a
      promising approach in immunotherapy of cancer. It has been demonstrated that
      Listeria monocytogenes activated DCs pulsed ex vivo with tumor antigens trigger a
      systemic Th1-biased specific immune response and a single dose of this vaccine
      will cause a considerable anti tumor immunity. OBJECTIVE: The present study was
      designed to evaluate the ability of multiple doses of tumor antigen-pulsed DCs,
      matured in the presence of Listeria monocytogenes components in induction of a
      potent anti-tumor response and the prevention of tumor formation in an
      experimental model. METHODS: Bone-marrow derived DCs (BMDCs) were cultured in the
      presence of GM-CSF and IL-4. After 5 days, tumor lysates with/without Listeria
      monocytogenes lysate were added to the culture media for another 2 days. Mice
      received mature and tumor antigen pulsed dendritic cells subcutaneously in 3
      groups. Tumor growth was monitored and two weeks after immunotherapy, cytotoxic
      activity of CD8+ T cells was evaluated in different groups. RESULTS: According to
      the findings, repeated doses of vaccine did not lead to a significant increase in
      the activity of cytotoxic T cells and decreased tumor growth of immunized
      animals. CONCLUSION: The current study suggests that increased doses of vaccine
      do not have sufficient efficiency for prevention of tumor induction. Generation
      of T regulatory responses upon repeated doses of such vaccines should be
      considered in future investigations.

PMID- 18319524
TI  - Antitetanus toxoid antibody titer of chronic hemodialysis patients in Iran.
AB  - BACKGROUND: Patients with end stage renal disease have higher incidence of
      infection diseases that is thought to be related to impaired immune system.
      OBJECTIVE: To determine the antitetanus IgG antibody level in Iranian
      hemodialysis patients with end stage renal disease and to find its association
      with sex, age, blood hemoglobin, serum albumin, duration of dialysis, time of
      dialysis per week, dialysis adequacy, erythropoietin, or iron supplementation,
      body mass index (BMI) and underlying renal disorder. METHODS: We conducted a
      cross sectional study on a total of 108 Iranian hemodialysis patients with end
      stage renal disorder, and 36 healthy individuals in the control group matched
      with the patient group. The patients and controls did not receive any antitetanus
      vaccine or immunoglobulins a year prior to the investigation. The serum
      antitetanus IgG antibody levels were measured by an ELISA method. RESULTS: We
      found 74.3% of patients to have unprotected antitetanus IgG antibody level
      compared with 52.8% of the control group. Except hemodialysis duration, none of
      the contributing factors seemed to affect immunity. CONCLUSION: We conclude that
      in our study, there is a significant difference in the antitetanus IgG antibody
      level between hemodialysis patients and the control group and also in the chronic
      hemodialysis patients.

PMID- 18319525
TI  - High sensitivity C-reactive protein and immunoglobulin G against Chlamydia
      pneumoniae and chlamydial heat shock protein-60 in ischemic heart disease.
AB  - BACKGROUND: Inflammation and infectious agents such as Chlamydia pneumoniae have
      been associated with cardiovascular disease. OBJECTIVE: To evaluate the serum
      high sensitivity C-reactive protein (hs-CRP) and antibodies against Chlamydia
      pneumoniae and Chlamydial heat shock protein-60 (Cp-HSP-60) in patients with
      ischemic heart disease (IHD). METHODS: 62 patients with IHD having either acute
      myocardial infarction (AMI; n=31) or unstable angina (UA; n=31) and 31 sex- and
      age- matched healthy subjects as a control group were enrolled in this study.
      Serum samples of participants were tested for the presence of hs-CRP and
      antibodies against C. pneumoniae and Cp-HSP-60 using ELISA method. RESULTS: The
      seroprevalence of anti-C. pneumoniae antibody in AMI group (93.5%) or UA group
      (90.3%) was significantly higher than the control group (61.3%; p<0.001). The
      seroprevalence of anti-Cp-HSP60 IgG was 22.6% in healthy subjects with mean end
      titer of 43.1+/-6.32. The seropositive rates of anti-Cp-HSP60 were 48.4%, 54.8%
      and 51.6% in AMI, UA and the overall IHD groups with mean end titers of 94+/
      22.86, 113.8+/-24.25 and 103.9+/-16.57, respectively. Both the seroprevalence and
      the mean titer of anti-Cp-HSP60 in patients groups were significantly higher than
      those observed in the control group (p<0.04 and p<0.03, respectively). Moreover,
      the mean serum hs-CRP levels was significantly higher in the IHD group as
      compared to the control group (21.6 microg/ml+/-3.73 vs 2.5 microg/ml+/-0.52;
      p<0.00001). The mean serum hs-CRP levels of AMI (30.3 microg/ml+/-6.07) or UA
      (12.9 microg/ml+/-3.85) groups were also significantly higher than those observed
      in the control group (p<0.00001 and p<0.001, respectively). Furthermore, the
      difference of the mean serum hs-CRP levels between AMI and UA groups was also
      significant (p<0.02). CONCLUSIONS: These results showed that the seroprevalence
      of antibodies against C. pneumoniae and Cp-HSP-60 and the serum levels of hs-CRP
      and anti-Cp-HSP60 IgG were higher in patients with IHD.

PMID- 18319526
TI  - Immunotherapy of Chenopodium album induced asthma by intranasal administration of
      CpG oligodeoxynucleotides in BALB/c mice.
AB  - BACKGROUND: There are many therapeutic methods for allergic conditions. CpG
      oligonucleotides play a critical role in immunity via the augmentation of Th1 and
      suppression of Th2 responses. OBJECTIVE: In the present study we aimed to
      estimate the effectiveness of intranasal administration of CpG ODN plus
      Chenopodium album allergen in allergic asthma compared with the administration of
      allergen alone and to find out how CpG ODN therapy is useful in the treatment of
      allergen induced asthma. METHODS: BALB/c Mice were intraperitoneally and
      intranasally sensitized with allergenic extract precipitated on aluminum
      hydroxide. Therapy with CpG/Ag was performed intranasally. After antigenic
      challenge, a number of Immunologic variables such as serum IgE and IgG, systemic
      and local IL-10 and IFN-gamma were studied in splenocytes, and lung tissue
      culture supernatants, respectively. RESULTS: Our study indicated that intranasal
      administration of CpG/Ag had significant increases in both systemic and local
      levels of IL-10 and IFN-gamma (p <or= 0.001), but showed no significant effect on
      the levels of IgE, IgG2a, and IgG1 in serum (p=0.06). This study demonstrated
      that CpG ODN has therapeutic effects not only on splenocytes but also on nasal
      lymphocytes to produce IFN-gamma as a Th1 cytokine, and IL-10 as a regulatory
      cytokine. CONCLUSION: According to these data from the mouse model, we conclude
      that intranasal administration of CpG motifs before allergen exposure may be
      useful for the control of allergic asthma. Therefore, further investigations on
      humans using CpG motifs are recommended in order to modulate the allergic effects
      of Chenopodium album as well as other regional allergens.

PMID- 18319527
TI  - Co-existence of common variable immunodeficiency (CVID) with idiopathic
      thrombocytopenic purpura (ITP).

PMID- 18319528
TI  - Anticardiolipin and antiphospholipid antibodies in Iraqi patients with angina
      pectoris.

PMID- 18319530
TI  - Life time risk for development of ten major cancers in India and its trends over
      the years 1982 to 2000.
AB  - BACKGROUND: Understanding cancer magnitude, risk and trends will be of help in
      cancer control programs. AIM: To study trends in cumulative risk up to 64 years
      of age as lifetime risk of developing major cancers in India during the years
      1982 to 2000. DESIGN: Retrospective. SETTING: Secondary sources of cancer
      registration data. MATERIALS AND METHODS: Data on age-specific cancer-incidence
      rates were collected for patients 0-64 years of age of either sex for 10 major
      cancer sites from the National Cancer Registry Program (NCRP) reports of India
      from Mumbai, Chennai, Bangalore, Bhopal and Delhi; and Barshi registries for the
      years 1982 or 1988 to 2000. STATISTICAL ANALYSIS: Cumulative risks computed for
      lifetime development of cancer. Linear trends were studied using simple linear
      regressions. RESULTS: The lifetime risk among females for the 10 cancer sites
      ranged from 0.02 to 3.3% and from 0.04 to 2.4% for the years 1982 and 2000
      respectively; whereas among males, it ranged from 0.04 to 0.89% and from 0.05 to
      0.95% respectively. Significant (P<0.05) increasing trends were observed for
      breast, non-Hodgkin's lymphoma (NHL), gallbladder, thyroid and ovary cancers
      among females; while declining trends were observed for cervix, mouth, stomach,
      esophagus and tongue cancers. Among males, significant (P<0.05) increasing trends
      wre observed for NHL and prostate cancer; whereas declining trends were observed
      for stomach, liver, hypopharynx and tongue cancers. Cancers of mouth and
      esophagus showed increasing trends (P<0.05) in some regions and declining trends
      (P<0.05) in some other. CONCLUSION: Significant and higher rates of positive
      trends in lifetime cancer risks for breast cancer among females and for NHL among
      both sexes were observed.

PMID- 18319531
TI  - Epidemiological correlates of nutritional anemia among children (6-35 months) in
      rural Wardha, Central India.
AB  - BACKGROUND AND OBJECTIVES: Nutritional anemia is associated with impaired
      performance of a range of mental and physical functions in children, along with
      increased morbidity. Iron supplementation at a later age may not reverse the
      adverse effects. National Nutritional Anemia Control Program was launched in
      India in 1970, but it failed to make any impact. The present study was undertaken
      to find out prevalence of anemia and its correlates in rural Wardha in children 6
      35 months of age. MATERIALS AND METHODS: Seven hundred seventy-two children
      between 6 months and 35 months of age were studied for anemia by cluster-sampling
      method. The hemoglobin was estimated in the child by 'Filter paper
      cyanmethemoglobin method.' Pre-designed and pre-tested questionnaire was used to
      collect data on socio-demographic and other variables. Data was analyzed by SPSS
      12.0.1. RESULTS: Mean hemoglobin level was 98.5+/-12.9 gm/L. Prevalence of anemia
      was 80.3%. Only 1.3% children had severe anemia (hemoglobin<70 gm/L). The
      univariate analysis showed that anemia is significantly associated with age of
      the child, education of mother and father, occupation of father, socioeconomic
      status, birth order and nutritional status as measured by weight for age. The
      final model suggested that only educational status of the mother, occupation of
      the father, birth order and nutritional status of the child were significantly
      associated with anemia. INTERPRETATION AND CONCLUSION: For short-term impact,
      appropriate nutritional interventions remain the only operational intervention as
      only the nutritional status (weight for age) is a modifiable factor. But for long
      term sustained impact, policy makers need to focus on improving maternal
      education and reducing family size.

PMID- 18319532
TI  - Development of a scale for attitude toward condom use for migrant workers in
      India.
AB  - BACKGROUND: The propaganda for the use of condoms remains one of the mainstay for
      prevention of human immunodeficiency virus (HIV) transmission. In spite of the
      proven efficacy of condom, some moral, social and psychological obstacles are
      still prevalent, hindering the use of condoms. AIMS: The study tried to construct
      a short condom-attitude scale for use among the migrant workers, a major bridge
      population in India. SETTINGS AND DESIGN: The study was conducted among the male
      migrant workers who were 18-49 years old, sexually active and had heard about
      condoms and were engaged in nonformal jobs. We recruited 234 and 280 candidates
      for Phase 1 and Phase 2 respectively. MATERIALS AND METHODS: Ten items from the
      original 40-item Brown's ATC (attitude towards condom) scale were selected in
      Phase 1. After analysis of Phase 1 results, using principal component analysis
      six items were found appropriate for measuring attitude towards condom use. These
      six items were then administered in another group in Phase 2. Utilizing Pearson's
      correlations, scale items were examined in terms of their mean response scores
      and the correlation matrix between items. Cornbach's alpha and construct validity
      were also assessed for the entire sample. RESULTS: Study subjects were
      categorized as condom users and nonusers. The scale structure was explored by
      analyzing response scores with respect to the items, using principal component
      analysis followed by varimax rotation analysis. Principal component analysis
      revealed that the first factor accounted for 71% of the variance, with eigenvalue
      greater than one. Eigenvalues of the second factor was less than one. Application
      of screen test suggests only one factor was dominant. Mean score of six items
      among condom users was 20.45 and that among nonusers was 16.67, which was
      statistically significant (P<0.01). Cornbach's alpha coefficient was 0.92.
      CONCLUSION: This tailor-made attitude-toward-condom-use scale, targeted for most
      vulnerable people in India, can be included in any rapid survey for assessing the
      existing beliefs and attitudes toward condoms and also for evaluating efficacy of
      an intervention program.

PMID- 18319533
TI  - Myasthenic crisis-like syndrome due to Cleistanthus collinus poisoning.
AB  - Poisoning with Cleistanthus collinus frequently causes cardiac manifestations
      such as rhythm disturbances and also results in other manifestations such as
      metabolic acidosis and hypokalemia. We present the case of a patient who
      presented with a rare myasthenic crisis-like syndrome requiring assisted
      ventilation due to Cleistanthus collinus poisoning, which responded to treatment
      with neostigmine.

PMID- 18319534
TI  - Unusual associations of pachydermoperiostosis: a case report.
AB  - Primary hypertrophic osteoarthropathy (HOA), or pachydermoperiostosis, is a rare
      benign disorder of unknown etiology. It is characterized by clubbing, periosteal
      reaction, and thickening of the skin. Disease usually progresses slowly, and
      natural arrest may occur. Reported herein is the case of a 28-year-old male
      patient with progressively increasing swelling of large joints of lower limbs
      with severe anemia. He was diagnosed as a case of pachydermoperiostosis with
      myelofibrosis, which is a rare association. The development of myelofibrosis
      makes primary HOA a disease with unfavorable outcome.

PMID- 18319535
TI  - Acute disseminated encephalomyelitis after treatment of severe falciparum
      malaria.

PMID- 18319536
TI  - An unusual complication of Plasmodium falciparum malaria.

PMID- 18319537
TI  - E-endocrinology: an update.
AB  - Internet, from a long time, has opened up a myriad resource of knowledge and
      applications for academicians, researchers and clinicians alike in all health
      care professions across the globe. Basic endocrinologists are exploring through
      bench-top protocols to understand endocrine system and to design therapeutic
      interventions. Clinicians are required to continuously look for new developments
      relating to investigation, diagnosis and therapeutic options in their everyday
      practice for better quality of life of patients. All these require managing a
      large body of information. Now, these innovative technologies have opened up
      newer avenues for endocrinologists. As internet is serving the backbone for
      modern technologies, it is of utmost necessity to use and refine internet
      applications for future endocrinologists. Increasingly, easy access to internet
      has dramatically reduced barriers in sharing information among basic and clinical
      endocrinologists. Considering the growing scope for endocrinologists in the use
      of internet, it is necessary to understand internet as a source of information
      and backbone of modern applications. This review illustrates the expanding roles
      of the internet for endocrinologists and provides a ready-to-use compilation of
      useful academic, research, clinical resources, and is expected to introduce,
      stimulate and guide endocrinologists into the realm of WWW.

PMID- 18319538
TI  - Metabolic syndrome.

PMID- 18319539
TI  - Vitamin A and sleep regulation.
AB  - Vitamin A is the parent compound of retinoids, which regulate gene transcription
      by binding to nuclear retinoid receptors. Recently, it has been suggested that
      retinoid signaling pathways are important for adult neural function in health and
      disease. In this mini review we will summarize the molecular pathway of retinoid
      and experimental data on this pathway relating to sleep regulation, which
      suggests that retinoid signaling mechanism may be involved in the homeostatic
      component of sleep electroencephalogram.

PMID- 18319540
TI  - Regulation of epithelial cell adhesion and repulsion: role of endocytic
      recycling.
AB  - A proper balance between cell adhesion and repulsion is essential for cellular
      morphogenesis during epithelial-mesenchymal transition and mesenchymal-epithelial
      transition. A number of ligand-receptor pairs including hepatocyte growth
      factor/scatter factor-Met and semaphorin-plexin are known to control this balance
      through the complex intracellular signaling pathways. Cell adhesion to other
      cells and extracellular matrix (ECM) is mediated by cell adhesion molecules
      (CAMs) and ECM receptors, respectively, which are associated with cytoskeleton
      through a variety of plaque proteins strengthening and/or weakening adhesion
      activities. Cell repulsion requires the downregulation of cell adhesion and the
      extensive changes in cytoskeletal dynamics. The endocytic recycling of CAMs and
      ECM receptors has recently emerged as an important mechanism to control the
      balance between cell adhesion and repulsion. Molecule interacting with CasL
      (MICAL) family proteins are originally identified as a plaque protein associated
      with ECM receptors integrins and implicated in semaphorin-plexin dependent
      repulsive axon guidance. We have recently shown that MICAL family protein
      JRAB/MICAL-L2 functions as an effector protein for Rab family small G protein
      Rab13 and regulates the endocytic recycling of tight junctional CAM occludin and
      controls the adhesion and repulsion of epithelial cells.

PMID- 18319541
TI  - Optimal therapy for thymoma.
AB  - Thymoma is the most common tumor of the anterior mediastinum. This tumor is
      associated with unique paraneoplastic syndromes (myasthenia gravis, pure red cell
      aplasia, hypogammaglobulinemia, and other autoimmune diseases). The rarity of
      this tumor has somewhat obscured the optimal treatment. Although the histologic
      classification of thymoma has remained a subject of controversy for many years,
      the WHO classification system, published in 1999, appeared to be an advance in
      our understanding of thymoma. The optimal treatment for thymoma depends on its
      clinical stage. Surgery remains the mainstay of treatment for thymic epithelial
      tumors. Thymomas also have a high response rate to chemotherapy or radiotherapy.
      Only surgical resection is performed for patients with stage I (non-invasive)
      thymoma. The value of postoperative radiotherapy in completely resected stage II
      or III tumors is questionable. Multimodality therapy involving surgery,
      chemotherapy and radiotherapy appears to increase the rate of complete resection
      and survival in advanced (stage III and IV) thymomas.

PMID- 18319542
TI  - Longitudinal analysis of low-molecular weight fluorophores in type 1 diabetes
      mellitus.
AB  - OBJECTIVES: Circulating low molecular weight (<10 kDa) fluorophores (LMW-F)
      measured by non-specific fluorescence spectroscopy may detect small advanced
      glycation end-products (AGEs) not recognized by other assays. This longitudinal
      study assessed correlates of LMW-F and predictive power of LMW-F levels for
      vascular health in Type 1 diabetes (T1DM) patients. METHODS: Fasting patients
      with T1DM (n=37) were studied twice at intervals of 12-60 months (mean+/-SD, 33+/
      15 months). LMW-F levels were also measured once in 112 healthy control subjects.
      RESULTS: Relative to controls, LMW-F levels were higher in diabetic subjects at
      initial and final time points (mean+/-SD), 5.4+/-1.9 AU/ml and 4.5+/-1.8 AU/ml
      respectively vs. 3.8+/-2.1 AU/ml; p=0.0001 and p=0.06). Baseline LMW-F levels
      predicted subsequent hs-CRP and oxLDL/LDL values. LMW-F levels decreased
      significantly over time in diabetes (5.4+/-1.9 vs. 4.5+/-1.8 AU/ml; p=0.02).
      Rises in LMW-F levels in individual diabetic subjects correlated significantly
      with worsening renal function (BUN), glycemia (HbA1c) and with vascular
      dysfunction (systemic vascular resistance). CONCLUSIONS: LMW-F levels predict
      levels of inflammation and oxidation in T1DM. Changes in LMW-F levels in T1DM
      reflect variations in glycemia and renal function. Biochemical characterization
      of LMW-F would facilitate understanding of the potential utility of LMW-F as a
      therapeutic target.

PMID- 18319543
TI  - Effect of mediastinal lymph nodes sampling in patients with clinical stage I non
      small cell lung cancer.
AB  - OBJECTIVE: Systematic nodal dissection has been recommended for patients with
      resectable non-small cell lung cancer because of its staging accuracy. However,
      in patients with clinical stage I non-small cell lung cancer whether systematic
      nodal dissection provides more benefits than mediastinal lymph node sampling or
      not is controversial. In this retrospective study, we evaluated the effect of
      mediastinal lymph node sampling in patients with clinical stage I NSCLC. METHODS:
      One hundred and nineteen consecutive patients with clinical stage I NSCLC, who
      underwent curative operation between January 1994 and December 2000, were
      retrospectively reviewed (dissection group = 58: sampling group= 61). Systematic
      nodal dissection was defined as complete removal of mediastinal lymph node, and
      mediastinal lymph node sampling was defined as removal of lymph node levels 3, 4,
      and 7 for right-sided tumors and levels 5, 6, and 7 for left-sided tumors.
      RESULTS: The total number of removed mediastinal lymph nodes in patients who
      underwent systematic nodal dissection was 22.1 +/- 9.7, which was significantly
      higher than that in patients who underwent mediastinal lymph node sampling of
      11.4 +/- 7.0 (p < 0.001). Postoperatively N2 disease was detected in 8 patients
      (13.8%) in the dissection group and 7 (11.5%) in the sampling group. After the
      median follow up of 79 months, the cancer specific survival rate at 5 year was
      78.0% in the dissection group and 76.2% in the sampling group (p = 0.60).
      CONCLUSIONS: Mediastinal lymph node sampling showed the similar effect to
      systematic nodal dissection in patients with clinical stage I non-small cell lung
      cancer.

PMID- 18319544
TI  - Determination of the side-separated pulmonary right-to-left shunt volume.
AB  - BACKGROUND: With the present method of intrapulmonary right-to-left shunt volume
      calculation, no differentiation can be made between the shunt volume shares of
      the right and left lungs. For a better understanding of pathophysiological
      processes during thorax surgery with side-separated ventilation, a side-separated
      shunt volume determination would be useful. MATERIALS AND METHODS: In 14 young
      female pigs, catheters were implanted into the left atrium after left
      thoracotomy. After transient clamping of the ipsilateral pulmonary veins,
      pulmonary venous blood was selectively obtained from the right lung. Cardiac
      output (CO) and side-separated pulmonary perfusion were determined with
      flowprobes at the pulmonary trunk and the left pulmonary artery. The shunt
      volumes were determined before and after thoracotomy during two-lung ventilation
      (Two-LV), after one-lung (right) ventilation (One-LV) with a continuous positive
      airway pressure (CPAP) of +7.5, +5.0 cm H(2)O, and under atelectasis of the non
      dependent left lung (NDL). RESULTS: After thoracotomy in lateral decubitus
      position and Two-LV, the shunt volumes of the two lungs differ. The right lung
      holds the major share (11.0 +/- 1.7% CO) [mean +/- SD]. The share of the left NDL
      is only 3.3 +/- 1.4. Under One-LV (right) and CPAP in the NDL, the total
      pulmonary shunt volume rises. This is caused by the increase in the NDL shunt
      volume share to 8.8 +/- 5.2 under CPAP +7.5 (p<0.05) and to 9.7 +/- 2.5 under
      CPAP +5.0 (p < 0.05). CONCLUSIONS: The new intraoperative method of side
      separated arterial blood gas analysis in conjunction with side-separated
      perfusion measurement makes side- separated right-to-left shunt volume
      determination possible and may lead to interesting new pathophysiological
      insights.

PMID- 18319545
TI  - Transconjunctival sutureless 25-gauge vitrectomy with newly designed
      microcannulas.
AB  - AIM: To evaluate the usefulness of the newly designed 25-gauge (25-G)
      microcannula for transconjunctival sutureless vitrectomy (TSV). METHODS: 25-G TSV
      was performed on 20 consecutive eyes with the newly designed 25-G microcannulas.
      We studied usefulness, intraoperative and postoperative complications in these
      cases. RESULTS: No complications were recognized during surgery. Postoperative
      complications included blebs in five eyes, vitreous hemorrhage in one eye, high
      intraocular pressure (more than 22 mmHg) in one eye and a retinal tear in one
      eye. No eyes with low intraocular pressure (less than 10 mmHg) were noted.
      CONCLUSIONS: This microcannula for 25-G vitrectomy is thought to be very useful
      and effective for performing 25-G vitrectomy safely.

PMID- 18319546
TI  - Thymidine phosphorylase and dihydropyrimidine dehydrogenase are predictive
      factors of therapeutic efficacy of capecitabine monotherapy for breast cancer
      preliminary results.
AB  - Capecitabine monotherapy was administered for 25 patients with advanced or
      recurrent breast cancer, and the clinical therapeutic efficacy and its
      relationship to expression of 5-fluorouracil-related enzymes (i. e., thymidine
      phosphorylase (TP), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase
      (DPD)) were investigated. The expressions of TP, TS and DPD were determined by
      immunohistochemical staining techniques and rated using a scoring system of 1~4.
      The expression score for TP/DPD showed a statistically significant correlation
      with the clinical response, whereas the expression score for TP/TS also showed a
      correlation but it was not statistically significant. The number of patients was
      small, but the results revealed the potential of application of the TP/DPD
      expression score as a factor for predicting the efficacy of the drug in
      individual patients.

PMID- 18319547
TI  - NO-1886, a lipoprotein lipase activator, attenuates contraction of rat intestinal
      ring preparations.
AB  - Various intestinal symptoms or diseases are closely associated with intestinal
      motility, which may be altered by metabolic disturbances associated with diabetes
      and obesity. It is therefore important that drugs used in the treatment of
      metabolic disorders should not have any adverse effects on the intestine. In the
      present study, we examined whether [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]
      phosphonic acid diethyl ester (NO-1886), a lipoprotein lipase activator with anti
      diabetic and/or anti-obese activity, affects stimulant-induced intestinal
      contractility. Administration of NO-1886 to intestinal ring preparations of
      ileum, rectum and colon isolated from Wistar rats attenuated or relaxed
      contraction induced by a high K+ environment or acetylcholine (ACh). This effect
      of NO-1886 was dependent on extracellular Ca(2+) and intracellular myosin light
      chain kinase activity. Our results also showed that ACh-induced colonic
      contraction was significantly higher in the obese Otsuka Long-Evans Tokushima
      Fatty (OLETF) than in the non-obese Long-Evans Tokushima Otsuka (LETO) rats. The
      hypercontractility observed in the colons of OLETF rats occurred concomitantly
      with an elevation in muscarinic M3 ACh receptor protein levels. Administration of
      NO-1886 attenuated the obesity-induced hypercontractility of the colonic rings of
      OLETF rats. Thus, intestinal contractile system would be a novel pharmacological
      target of the lipoprotein lipase activator NO-1886.

PMID- 18319548
TI  - Effects of lifestyle habits and eating meals together with the family on the
      prevalence of obesity among school children in Tokushima, Japan: a cross
      sectional questionnaire-based survey.
AB  - Obesity in children has become a major global public health concern. The
      prevention of obesity must start from early childhood in order to establish sound
      lifestyle habits and promote healthy adulthood. In this study, we evaluated
      factors associated with the prevention of obesity and the development of healthy
      lifestyle habits in children. A cross-sectional, questionnaire-based survey was
      performed in elementary and junior high school students in Tokushima Prefecture,
      Japan, during the summer of 2004. The questionnaire consisted of 30 items such as
      physique, sleep, eating habits, diet, exercise, free time, and attending after
      school lessons. Our study revealed that eating meals as a family every day is
      associated with a lower rate of obesity as well as getting good lifestyle habits
      such as eating balanced meals and getting enough sleep. Of the 3,291 students who
      responded to the questionnaire, 2,688 (81.7%) reported that they eat meals with
      their family every day. The percentage of students who eat meals with their
      family every day decreased with increasing school grade, with the lowest percent
      in the junior high school students. However, the results regarding female junior
      high school students revealed a marked association between eating meals with the
      family every day and good lifestyle habits. We recommend that parents and school
      teaching staff encourage the establishment of sound, healthy lifestyle habits in
      children from early childhood as an effective measure for the prevention of
      obesity.

PMID- 18319549
TI  - Prognostic significance of HIF-2alpha expression on tumor infiltrating
      macrophages in patients with uterine cervical cancer undergoing radiotherapy.
AB  - Hypoxia-inducible factor (HIF)-2alpha, a basic helix-loop-helix (bHLH)-PAS
      protein, is the principal regulator of the hypoxic transcriptional response. An
      immunohistochemical study reported strong HIF-2alpha expression in the cytoplasm
      of tumor infiltrative macrophages (TIMs). Thus we assessed the expression of HIF
      2alpha in human cervical cancer tissue before radiation therapy and its
      relationship to the clinical outcome. Seventy three patients with histologically
      proven primary advanced squamous cell carcinoma of the uterine cervix underwent
      radiotherapy in Tokushima University Hospital after biopsy specimens were taken.
      Among 73 specimens stained for HIF-2alpha, 53 (72.6%) exhibited HIF-2alpha
      immunoreactivity in the TIMs. In only 5 of 73 cases, HIF-2alpha immunoreactivity
      was observed in the nuclei of tumor cells. The HIF-2alpha positive cell count
      ratio in TIMs was associated with disease-free survival (DFS) with the worst DFS
      (p=0.024) being in cases in the group with a high positive cell count ratio. A
      high HIF-2alpha positive cell count ratio in TIMs increased the risk of local
      recurrence (p=0.0142). These findings might suggest that the ratio of the HIF
      2alpha positive cell in TIMs may be a new predictive indicator for prognosis
      before radiation therapy for uterine cervical cancer.

PMID- 18319550
TI  - Sp6 downregulation of follistatin gene expression in ameloblasts.
AB  - Sp6 is a member of the Sp family of transcription factors that regulate a wide
      range of cellular functions, such as cell growth and differentiation. Sp6, also
      called epiprofin, is specifically expressed in tooth germ, limb bud, and hair
      follicle, but there is little information on its function.To investigate the
      possible role of Sp6 in tooth development, first we established an Sp6
      overproducing clone, CHA9, and analyzed the features of the cell, including cell
      proliferation and gene expression. The parental cells of CHA9 are the ameloblast
      lineage G5 cells that we previously established from rat dental epithelia of
      lower incisor. Sp6 overproduction accelerated cell proliferation and induced the
      expression of ameloblastin mRNA, a marker of ameloblast differentiation. Second,
      we performed genome-wide screening of Sp6 target genes by microarray analysis.
      Out of a total 20,450 genes, 448 genes were up-regulated and 500 genes were down
      regulated by Sp6. We found the expression of follistatin, a BMP antagonist, to be
      22.4-fold lower in CHA9 than in control cells. Transfection of the Sp6-antisense
      construct into CHA9 cells restored follistatin expression back to equivalent
      levels seen in control cells, indicating that Sp6 regulates follistatin gene
      expression in ameloblasts. Our findings demonstrate that the follistatin gene is
      one of the Sp6 target genes in ameloblasts and suggest that Sp6 promotes
      amelogenesis through inhibition of follistatin gene expression.

PMID- 18319551
TI  - Can Kampo therapy prolong the life of cancer patients?
AB  - Our policy regarding the performance of radiotherapy to squamous cell carcinoma
      of the uterine cervix has not changed since 1969. We have already reported the
      treatment results which were as good as those from other institutions. Since
      1978, Kampo therapy was first introduced in the treatment of cancer patients in
      dealing with problems such as the side effects of radiotherapy and chemotherapy
      and various types of general malaise. We analyzed our treatment results in order
      to re-evaluate the chemo-radiotherapy in combination with Kampo. Survival rates
      for 5, 10 and 15 years, respectively, were 90.9%, 71.6% and 71.6% for Stage IB,
      78.9%, 61.8% and 41.8% for Stage II, 62.3%, 49.1% and 41.2% for Stage III and
      53.1%, 36.5% and 16.7% for Stage IV. The Kampo significantly extended the
      survival of patients with uterine cervical cancer. We intend to perform further
      research with more patients to explore how this therapy contributes to the
      prolonging of patients survival.

PMID- 18319552
TI  - Prognostic significance of serum hepatocyte growth factor in clear cell renal
      cell carcinoma: comparison with serum vascular endothelial growth factor.
AB  - No adequate serum predictive biomarker currently exists, which can identify the
      activity of renal cell carcinoma (RCC). We investigate the association of serum
      hepatocyte growth factor (HGF) and serum vascular endothelial growth factor
      (VEGF) levels with clinicopathologic parameters in untreated clear cell RCC
      patients. We measured serum levels of HGF and VEGF in 45 patients with untreated
      clear cell RCC and 45 healthy controls using an enzyme-linked immunosorbent assay
      (ELISA). Patients with clear cell RCC had significantly higher serum HGF and VEGF
      concentrations than healthy subjects: median, 1070.7 versus 728.3 pg/ml
      (p<0.0001) for HGF; and median, 397.5 versus 245.6 pg/ml (p=0.0003) for VEGF. We
      found a significant correlation between serum level of HGF and clinical stage and
      tumor grade. Survival of patients with high serum HGF (>1150 pg/ml) was
      significantly reduced compared to patients with low serum HGF concentrations
      (p=0.0044). In patients with nuclear grade 2 or high stage RCC, the higher serum
      HGF group exhibited significantly lower cause-specific survival (p=0.0087 and p<
      0.05, respectively). No significant difference was observed between serum VEGF
      levels and cause-specific survival rate. Serum HGF might be a diagnostic and
      prognostic indicator in clear cell RCC, especially for patients with grade 2 or
      high stage RCC.

PMID- 18319553
TI  - Observations on the occurrence of exacerbations in clinical course of systemic
      lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a chronic disease that is characterized by
      an undulating course of exacerbations and remissions, and a major determinant of
      long-term prognosis is organ damage consequent to tissue injury that accompanies
      disease activity and toxicity of therapy. In this study, we evaluated which
      patients with SLE will develop an exacerbation and whether factors can be
      identified to predict the development of an exacerbation. Fifty-seven SLE
      patients (52 females) were included in this study. The exacerbation of SLE was
      found in 15 patients (26.3%). A relatively increased incidence of an exacerbation
      was found in younger SLE patients. An increased percentage of patients who had
      lupus nephritis at the time of diagnosis of SLE was found in patients with a
      subsequent exacerbation when compared with that in those without it. Increased
      incidence of an exacerbation was observed in patients who had decreased number of
      WBC and platelets, decreased level of C3 and CH50, and the presence positivity of
      anti-Sm antibodies at the time of the diagnosis. This study suggests that age,
      renal involvement, and the presence of decreased number of WBC and platelets,
      decreased level of complements anti-Sm antibodies are predictors of exacerbation.

PMID- 18319554
TI  - Analyses of the characteristics of potential and cross-talk at each electrode in
      electro-oculogram.
AB  - We placed negative electrodes on the body and positive electrodes at the medial
      and lateral canthi, measured their potentials separately, evaluated their
      characteristics, and analyzed cross-talk. We recorded EOG in 6 normal subjects
      and found the following. The potential at the medial was lower than that at the
      lateral canthus in the bilateral eyes. The polarity of waves at the lateral was
      reverse to that at the medial canthus in the bilateral eyes. We recorded EOG in 6
      patients with unilateral anophthalmia and found the following. On the
      anophthalmia side, the potential at the lateral was considerably lower than that
      at the medial canthus. The polarity of the potential was the same between the
      medial and lateral canthi. The mean cross-talk to the medial canthus on the
      anophthalmia side was 8.7%-54.0% of the potential at the medial canthus on the
      normal side. The mean cross-talk to the lateral canthus on the anophthalmia side
      was 4.4%-16.9%. The influence of cross-talk of the other eye was marked at the
      medial but slight at the lateral canthus. In EOG recording, results with minimum
      errors due to cross-talk can be obtained by paying attention to the potential at
      the lateral canthus.

PMID- 18319555
TI  - Serum level of galectin-3 in human bladder cancer.
AB  - We examine serum level of galectin-3 in patients with bladder cancer. We used
      serum samples of 67 patients with urological diseases and classified these
      patients into bladder cancer group (n=43) and control group (n=24). Galectin-3
      concentration was measured by ELISA (Human Galectin-3 Assay Kit, IBL). And we
      selected the patient with high serum galectin-3 concentration (Urothelial
      Carcinoma, G3, pT3a pN0M0), we performed immunohistochemical staining with the
      VECTASTAIN ABC (Avidin Biotinylated enzyme Complex) system. Median value of serum
      galectin-3 concentration was 1068 pg/ml (range 551-2028) in the cancer group vs
      584 pg/ml (range 259-1262) in controls. Serum galectin-3 concentration of the
      bladder cancer patients was statistically higher than that of controls
      (p<0.0005). There was no apparent correlation in serum galectin-3 concentration
      with the clinico-pathological features such as stage and grade. Higher expression
      of galectin-3 was observed in bladder cancer tissue than in normal bladder
      tissue. We suggest the measurement of serum galectin-3 is useful for diagnosis of
      bladder cancer.

PMID- 18319556
TI  - Opposing effects of estradiol and progesterone on the oxidative stress-induced
      production of chemokine and proinflammatory cytokines in murine peritoneal
      macrophages.
AB  - In inflammatory and oxidative liver injury, virus proteins and reactive oxygen
      species are involved in the regulation of proinflammatory cytokine production by
      macrophages. This study investigated the effects of estradiol (E2) and
      progesterone on the unstimulated and oxidative stress-stimulated production of
      tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, macrophage
      inflammatory protein (MIP)-2, and macrophage chemotactic protein (MCP)-1 by
      peritoneal macrophages isolated from male and female mice. E2 inhibited the
      cytokine production of TNF-alpha, IL-1beta, MIP-2, and MCP-1 by the unstimulated
      macrophages from males and females, which was then further stimulated by
      progesterone. The exposure to hydrogen peroxide in the macrophages from both
      sexes induced the production of cytokine. The hydrogen peroxide-stimulated
      cytokine production was suppressed by E2 and enhanced by progesterone. The sex
      hormone effects on the unstimulated and stimulated macrophages were blocked by
      their receptor antagonists and showed no significant difference between male and
      female subjects. These findings suggest that E2 may play a favorable role in the
      course of persistent liver injury, by inhibiting proinflammatory cytokine
      production, which, in addition, progesterone may counteract the favorable E2
      effects through their receptors.

PMID- 18319557
TI  - Autopsy case of rapid progressive atypical carcinoid of the lung discovered with
      multiple nodular shadows.
AB  - We report an autopsy case of rapid progressive atypical carcinoid of the lung
      discovered as multiple nodular shadows. The patient was an 82-year-old man with
      non-productive cough. Both chest radiography and computed tomography revealed
      multiple nodules in both the lung and pleural effusion. Multiple metastases to
      bone and liver were also noted. Samples from the wall-side pleural lesion were
      obtained by video-assisted thoracoscopic surgery under local anesthesia, and
      histological examination led to a diagnosis of atypical carcinoid. Treatment was
      ineffective and the patient died on day 39 after admission. The primary site was
      identified as the lung after autopsy. We believe that early detection is crucial
      in the treatment of atypical carcinoid due to poor prognosis.

PMID- 18319558
TI  - Laparoscopy and intersex: report of 5 cases of male pseudohermaphroditism.
AB  - From May, 1999 to August, 2006, we performed laparoscopic diagnosis and treatment
      for 103 cases of impalpable testes. Among those we found 5 cases of male
      pseudohermaphroditism of different etiologies. Three males presented by
      impalpable testes with ambiguous genitalia and 2 females presented by primary
      amenorrhea. All of them have 46-XY normal male chromosomal pattern. In the first
      3 cases, the etiology was complete gonadal dysgenesis, and 2 cases with
      persistent Mullerian syndrome. Timed gonadectomy for the first case and
      laparoscopic orchiopexy for the other 2 cases were performed. For the other 2
      female cases, the etiology was complete androgen insensitivity syndrome and
      laparoscopic bilateral orchiectomy was performed for both of them. All the
      procedures were done without complications with satisfactory results.

PMID- 18319559
TI  - Rare case of choroidal hemorrhage complicated with hypertension due to chronic
      renal failure.
AB  - BACKGROUND: Choroidal hemorrhage is usually seen as expulsive hemorrhage related
      to surgical invasion and is rarely observed in the absence of surgery or trauma.
      In this report, we describe a case of choroidal hemorrhage caused by hypertension
      related to chronic renal failure. CASE: A 32-year-old man presented with sudden
      visual loss, eye pain and swelling in his left eye. He had a history of renal
      failure and hypertension. Eye examination demonstrated choroidal hemorrhage
      associated with ocular hypertension in his left eye and marked hypertensive
      retinopathy in his right eye. OBSERVATIONS: He was treated with hemodialysis and
      antihypertensive drugs. Upon repeat eye examinations, a gradual reabsorption of
      the choroidal hemorrhage was observed, although vitreous hemorrhage appeared in
      the left eye. The vitreous hemorrhage was treated with vitrectomy with the
      patient regaining good visual acuity post-surgery. CONCLUSIONS: This rare case
      suggests that patients with severe background disease need to be carefully
      observed.

PMID- 18319560
TI  - Problems in three Japanese drug users with Human Immunodeficiency Virus
      infection.
AB  - Numbers of individuals infected with Human Immunodeficiency Virus (HIV) are
      increasing in Japan. The majority of them are Men who have sex with men and a
      part of them take drugs as 'Sex drug' at their sexual intercourse. Especially,
      Amyl nitrite, Methamphetamine, 5-methoxy-N, N-diisopropyltryptamine (5-MeO-DIPT;
      Foxy), and 3, 4-methylenedioxy- methamphetamine (MDMA; Ecstasy) are used, and
      they sometimes cause the physical and mental disorders. However, the actual drug
      inducing troubles among Japanese HIV-infected drug users had not yet been
      discussed enough. In this report, we describe three cases with HIV infection; a
      case developed severe neuroleptic malignant syndrome (NMS) after taking 5-MeO
      DIPT, a case with persistent convulsion due to multiple drug intake and a case
      with rhabdomyolysis due to the non-subjective methamphetamine intake. Through
      these cases, we raise and discuss several underlying problems associated with
      drug use among HIV-infected individuals.

PMID- 18319561
TI  - Cholangiolocellular carcinoma containing hepatocellular carcinoma and
      cholangiocellular carcinoma, extremely rare tumor of the liver:a case report.
AB  - Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor
      which was first defined by Steiner, et al. in 1957 (1). CLC is thought to be
      derived from Hering's canal because tumor glands of CLC are morphologically
      similar to cholangioles. Recently, Theise, et al. reported that Hering's canal
      might be composed of hepatic stem cells (3). In addition, CLC sometimes contains
      a hepatocellular carcinoma (HCC) or cholangiocellular carcinoma (CCC) component
      within the tumor. Those findings suggest that CLC might originate from hepatic
      stem cells. On the other hand, because of its low frequency, clinicopatholigical
      features of CLC have not been fully clarified yet. We herein report a case of a
      71-year old man with CLC. Based on preoperative imagings, the hepatic tumor was
      diagnosed as HCC, and he underwent a partial hepatectomy. The tumor contained
      both a HCC and CCC-like area. In immunohistochemistry, cytokeratin (CK) 7, CK20,
      CAM5.2 was positive, and CK19 was negative, therefore the tumor was diagnosed as
      CLC. The diagnostic criteria have not been described clearly, so CLC is difficult
      to diagnose preoperatively. Further studies are needed to clarify the clinical
      and clinicopatholigical features of CLC.

PMID- 18319562
TI  - Possible involvement of altered arginase activity, arginase type I and type II
      expressions, and nitric oxide production in occurrence of intimal hyperplasia in
      premenopausal human uterine arteries.
AB  - In the present experiments, we tried to elucidate whether changes in arginase
      activity and protein expression of arginase I and II are involved in the
      occurrence of intimal hyperplasia in premenopausal human uterine arteries. They
      were obtained from thirty-four patients undergoing total abdominal hysterectomy
      with informed consent for the present study. All specimens were assessed
      histologically and the intima/media ratio (%) was evaluated as an index of the
      intimal hyperplasia. Thirteen patients out of 34 had histologically normal
      arteries (intima/media ratio = 18.1 +/- 0.7%), whereas the remaining 21 patients
      had various degrees of intimal hyperplasia (intima/media ratio = 32.7 +/- 2.3%),
      and these specimens were categorized as hyperplasic. Intimal hyperplasia was
      accompanied by impaired cyclic GMP production, enhanced overall arginase
      activity, and up-regulations of arginase I and II in endothelial cells and of
      arginase II in the smooth muscle layer. Pearson's correlation coefficient
      analyses revealed the close relationships among the arginase activities in
      endothelial cells and smooth muscle layer, the intimal/media ratio, and cyclic
      GMP production. These results suggest that the enhanced arginase activity and
      expressions of two arginase subtypes shed new light on the processes associated
      with the occurrence of intimal hyperplasia in premenopausal human uterine
      arteries.

PMID- 18319563
TI  - A functional RNAi screen for Runx2-regulated genes associated with ectopic bone
      formation in human spinal ligaments.
AB  - Ossification of the posterior longitudinal ligament of the spine (OPLL) is
      characterized by ectopic ossification in the spinal ligaments, which enlarges
      with time and compresses the spinal cord, resulting in serious neurological
      symptoms. We previously reported that Runx2 expression was enhanced in spinal
      ligament cells from OPLL patients (OPLL cells). To clarify genes regulated by
      Runx2, Runx2 expression was first enhanced by culturing primary OPLL cells in
      osteogenic medium (OS induction) and then inhibited by siRNAs targeted to Runx2.
      DNA microarray demonstrated that in addition to chondrogenic factors such as
      connective tissue growth factor and cartilage oligomeric matrix protein,
      angiopoietin-1 was also significantly increased by OS induction and decreased by
      siRNAs for Runx2 in OPLL cells, suggesting that these genes are regulated by
      Runx2. However, these changes were not observed in non-OPLL control cells (from
      cervical spondylotic myelopathy patients). Furthermore, Runx2 was not decreased
      by siRNAs for angiopoietin-1. OS induction and RNAi inhibition of angiopoietin-1
      expression was also observed in osteoblasts. Both siRNAs for Runx2 and
      angiopoietin-1 completely inhibited aggrecan-1 expression. These results suggest
      that angiopoietin-1 is downstream of Runx2 in both OPLL primary cells and
      osteoblasts. Angiopoietin-1 may play an important role in ectopic ossification.

PMID- 18319564
TI  - Characteristics of gabexate mesilate-induced cell injury in porcine aorta
      endothelial cells.
AB  - Gabexate mesilate (GM), a serine protease inhibitor, often causes severe vascular
      injury, when injected in high concentration. In the present study, we
      investigated the mechanisms for the cytotoxicity of GM on porcine aorta
      endothelial cells (PAECs). GM (0.5 - 5.0 mM) decreased cell viability in a dose
      dependent manner and caused cell injury, whilst nafamostat mesilate (NM), another
      serine protease inhibitor, or mesilate itself had no effect on cell viability.
      zVAD-fmk, a pancaspase inhibitor, or zDEVD-fmk, a caspase-3 inhibitor, did not
      affect the GM (1.5 mM)-induced decrease of cell viability. Apoptotic cells or DNA
      fragmentation were also not observed after GM treatment. Moreover, Ca(2+)
      chelators, a nitric oxide (NO) synthase inhibitor, antioxidants, and radical
      scavengers had no effect on the GM-induced cell injury. On the other hand,
      cellular ATP content was decreased in the GM (2.0 mM)-treated cells.
      Surprisingly, GM (2.0 mM) immediately increased cellular uptake of propidium
      iodine. These findings suggest that GM induces necrotic cell death via injury of
      the cell membrane.

PMID- 18319565
TI  - Direct inhibition of N-methyl-D-aspartate (NMDA)-receptor function by
      antiglaucomatous beta-antagonists.
AB  - In the present study, we investigated the direct effects of antiglaucoma drugs
      (timolol, betaxolol, pilocarpine, and latanoprost) on N-methyl-D-aspartate (NMDA)
      receptor function using a Xenopus oocytes expression system and
      electrophysiological techniques. In oocytes expressing wild-type NMDA (NR1a/NR2A)
      receptors, timolol and betaxolol significantly inhibited glutamate-evoked
      currents, whereas less inhibition was obtained with pilocarpine, and latanoprost
      had few effects. Moreover, the effect of timolol and betaxolol was noncompetitive
      with respect to glutamate. Mutations that changed Asn616 of the NR1a subunit, a
      critical residue for Mg(2+) blocking of NMDA receptors, to Arg (N616R) or Gln
      (N616Q) almost eliminated the inhibitory effects of timolol and betaxolol, as
      well as the blocking effect of Mg(2+). Experiments were also carried out to
      examine the protective effects of timolol and betaxolol against death of oocytes
      expressing NMDA receptors. During incubation of oocytes, especially in Mg(2+)
      free medium, cell death was induced by addition of glutamate because of the
      continuous activation of the NMDA receptors expressed. Timolol and betaxolol
      significantly improved oocyte viability when they were added during the
      incubation period. These results suggest that timolol and betaxolol may have an
      additional role that they directly inhibit NMDA-receptor function, possibly via
      N616 of the NR1a subunit.

PMID- 18319566
TI  - Pharmacological characterization of the newly synthesized nociceptin/orphanin FQ
      receptor agonist 1-[1-(1-methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]
      1H-benzimidazole as an anxiolytic agent.
AB  - Nociceptin/orphanin FQ peptide (NOP)-receptor agonists have been shown to produce
      anxiolytic-like effects in rodents subjected to various behavioral assays.
      Recently, we developed a new nonpeptide agonist of the NOP receptor, 1-[1-(1
      methylcyclooctyl)-4-piperidinyl]-2-[(3R)-3-piperidinyl]-1H-benzimidazole
      (MCOPPB), as an anxiolytic agent. MCOPPB has a high affinity for the human NOP
      receptor (pKi = 10.07 +/- 0.01) and selectivity for the NOP receptor over other
      members of the opioid receptor family: 12-, 270- and >1000-fold more selective
      for the NOP receptor than for the micro-, kappa-, and delta-receptor,
      respectively. In an ex vivo binding study, MCOPPB (10 mg/kg, p.o.) inhibited
      signaling through the NOP receptor in the mouse brain, suggesting that it
      penetrated into the brain after it was orally administered. In the mouse Vogel
      conflict test, MCOPPB (10 mg/kg, p.o.) and diazepam (3 mg/kg, p.o.) elicited
      anxiolytic-like effects, although MCOPPB produced a bell-shaped response curve.
      In addition, MCOPPB (10 mg/kg, p.o.) was still effective as an anxiolytic agent
      even after repeated administration for 5 days. MCOPPB at an oral dose of 10 mg/kg
      did not affect locomotor activity or memory, nor did it contribute to ethanol
      induced hypnosis. On the other hand, the benzodiazepine-type anxiolytic agent
      diazepam caused memory deficits and enhanced ethanol-induced hypnosis. These
      findings suggest that MCOPPB - a compound with few adverse effects on the central
      nervous system - is a potential therapeutic agent for the treatment of anxiety.

PMID- 18319567
TI  - Phenoxazine derivatives inactivate human cytomegalovirus, herpes simplex virus-1,
      and herpes simplex virus-2 in vitro.
AB  - We examined whether phenoxazine derivatives, 2-amino-4,4alpha-dihydro-4alpha-7
      dimethyl-3H-phenoxazine-3-one (Phx-1), 3-amino-1,4alpha-dihydro-4alpha-8-dimethyl
      2H-phenoxazine-2-one (Phx-2), and 2-amino-phenoxazine-3-one (Phx-3) may have
      antiviral activity against herpes family viruses: human cytomegalovirus (HCMV),
      herpes simplex virus type 1 (HSV-1), and herpes simplex virus type 2 (HSV-2). The
      antiviral activity was evaluated by the selectivity index (SI), which is the
      ratio of 50% cytotoxic concentration (CC(50)) and 50% antiviral concentration
      (IC(50)). Among these phenoxazines, Phx-2 exerted strong antiviral activity to
      HCMV with the SI of 200, while Phx-1 and Phx-3 exerted no marked anti-HCMV
      activity. Phx-2 also showed moderate inhibition of HSV-1 and HSV-2, with the SI
      of 6.7 and 17, respectively. In the time-of-addition experiments, inhibitory
      effect of Phx-2 against HCMV was active even when applied to cells at 100 h after
      HCMV infection, while ganciclovir (GCV) showed potent inhibition when applied to
      cells before 42-h post-infection, but its inhibitory effects disappeared
      thereafter. Attachment and penetration of HCMV was not affected by the presence
      of Phx-2. When HCMV was pretreated with Phx-2, concentration-dependent virucidal
      action was observed, suggesting that Phx-2 inactivates HCMV directly. From these
      data, it was found that Phx-2 might have a different anti-HCMV target from GCV.

PMID- 18319568
TI  - Interactions of organic anion transporters and organic cation transporters with
      mycotoxins.
AB  - Mycotoxins are secondary metabolites of moulds that which exert adverse effects
      in humans and animals. It is known that direct cellular toxicity is often
      associated with increased cellular accumulation of toxic compounds, and membrane
      transport may be the first fundamental stage in the development of the
      cytotoxicity. To elucidate the entry pathway for mycotoxins into cells, we have
      investigated the interactions of human and rat organic anion transporters
      (hOATs/rOats) and human organic cation transporters (hOCTs) with mycotoxins using
      cells stably expressing hOATs/rOats/hOCTs. The mycotoxins tested were aflatoxin
      B1, alpha-zearalenol, citrinin, citrioveridine, cyclopiazonic acid, fumonisin B1,
      gliotoxin, patulin, penicillic acid, rubratoxin B, and zearalenone. These
      mycotoxins inhibited organic anion uptake mediated by hOAT1-4, and organic cation
      uptake mediated by hOCT1-2. By comparing the IC(50) values of mycotoxins for
      hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions
      with mycotoxins than hOAT2 and hOAT4. There was no interspecies difference
      between humans and rats for the interactions of OATs with mycotoxins except that
      of OAT3 with rubratoxin B. Finally, we observed that hOAT1-4 and hOCT1-2 mediated
      the uptake of aflatoxin B1. In conclusion, hOATs and hOCTs interacted with
      various mycotoxins. Considering the localization of hOATs/rOats and hOCTs, it was
      suggested that these transporters were the possible entrance pathway for
      mycotoxins in kidney and liver, leading to the induction of adverse effects in
      humans and rats.

PMID- 18319569
TI  - Heterologous gap junctions between granulosa cells and oocytes in ayu
      (Plecoglossus altivelis): formation and role during luteinizing hormone-dependent
      acquisition of oocyte maturational competence.
AB  - Gap junctions (GJs) are intercellular channels. Molecules with a molecular weight
      of 1 kDa or less can pass back and forth between adjacent cells through GJs.
      Communication between oocytes and the somatic cells that surround them via GJs is
      known to play key roles to initiate oocyte maturation in many vertebrates.
      However, little is known of the detailed functions of ovarian GJs during oocyte
      maturation in fish. The oocyte maturation of fish is induced by a maturation
      inducing steroid (MIS). The sensitivity of oocytes to the MIS is known as oocyte
      maturational competence (OMC) and is induced by luteinizing hormone (LH).
      However, LH receptors are found on the surface of granulosa cells rather than
      oocytes. We therefore proposed that the LH signals received by granulosa cells
      were passed to oocytes via GJs. This review describes current knowledge of the
      role of GJs between granulosa cells and oocytes during the LH-induced acquisition
      of OMC in fish.

PMID- 18319570
TI  - Health status and productive performance of somatic cell cloned cattle and their
      offspring produced in Japan.
AB  - Since the first somatic cell cloned calves were born in Japan in 1998, more than
      500 cloned cattle have been produced by somatic cell nuclear transfer and many
      studies concerning cloned cattle and their offspring have been conducted in this
      country. However, most of the results have been published in Japanese; thus, the
      data produced in this country is not well utilized by researchers throughout the
      world. This article reviews the 65 reports produced by Japanese researchers (62
      written in Japanese and 3 written in English), which employed 171 clones and 32
      offspring, and categorizes them according to the following 7 categories: (1)
      genetic similarities and muzzle prints, (2) hematology and clinical chemistry
      findings, (3) pathology, (4) growth performance, (5) reproductive performance,
      (6) meat production performance and (7) milk production performance. No
      remarkable differences in health status or reproductive performance were found
      among conventionally bred cattle, somatic cell cloned cattle surviving to
      adulthood and offspring of somatic cell cloned cattle. Similarities in growth
      performance and meat quality were observed between nuclear donor cattle and their
      clones. The growth curves of the offspring resembled those of their full
      siblings.

PMID- 18319571
TI  - C-reactive protein concentration in dogs with various diseases.
AB  - To investigate the clinical utility of C-reactive protein (CRP) determination in
      dogs, its plasma concentration was measured by a laser nephelometric method in
      928 dogs with various diseases, and was compared with other inflammatory
      parameters. CRP concentration was elevated in various inflammatory diseases, this
      was most frequently observed in cases with neoplastic and immune-mediated
      diseases. All cases of pyometra, panniculitis, acute pancreatitis, polyarthritis,
      and hemangiosarcoma showed significantly elevated CRP concentrations. On the
      other hand, the CRP concentration was elevated only in few cases of neurological
      diseases such as epilepsy, meningoencephalitis, and hydrocephalus and endocrine
      diseases such as hypothyroidism, hyperadrenocorticism, and diabetes mellitus.
      Only a weak correlation was observed between the CRP concentration and white
      blood cell (WBC) counts (r=0.44) but no correlation with band neutrophil counts.
      There was no correlation between the CRP and albumin concentrations, but a weak
      negative correlation (r=-0.40) when excluding chronic intestinal diseases and
      nephrotic syndrome, which can cause protein loss. Thus, CRP can be useful to
      detect inflammations that cannot be detected by WBC and, or band neutrophil
      counts, suggesting that the examination of CRP concentration is essential as
      routine diagnostic test.

PMID- 18319572
TI  - Histopathological characteristics of hepatic lipogranulomas with portosystemic
      shunt in dogs.
AB  - In the canine liver with portosystemic shunts (PSS), focal lesions consisting of
      cells with cytoplasmic brown pigments and lipid vacuoles are often observed in
      the hepatic parenchyma. Termed lipogranulomas, their histopathological
      characteristics have been little studied. In the present study, we examined liver
      biopsy samples from 144 dogs (age: 3 months-16 years; 65 PSS and 79 non-PSS
      cases), and investigated the histopathological characteristics, incidence, and
      density of lipogranulomas. Lipogranulomas were detected histopathologically in
      55.4% of PSS dogs. The lesions were then grouped into 3 types according to the
      amount of cytoplasmic lipid vacuoles and brown pigments. The pigments were
      positive for Berlin blue, PAS, and Sudan black B, but negative with the Hall
      method. The majority of the cells were immunohistochemically positive for
      macrophage scavenger receptor, class A (MSR-A), while no cells were positive for
      hepatocyte-antigen and albumin. The cytoplasmic pigments were recognized as
      electron-dense microgranular materials by electron microscopy. The incidence of
      lipogranulomas was significantly higher in the PSS group than non-PSS group when
      dogs less than 1 year old were excluded. The lipogranuloma density in the liver
      was significantly higher in the PSS group. It is concluded that lipogranulomas
      are frequently observed in liver biopsies of canine PSS especially in dogs more
      than 1 year old. The lesions consisted of Kupffer cells and/or macrophages, and
      the cytoplasmic brown pigments are ceroid and hemosiderin. The pathogenesis of
      lipogranuloma in PSS needs to be clarified.

PMID- 18319573
TI  - Functional disorder of the retina in manganese-deficient Japanese quail revealed
      by electroretinography using a contact lens electrode with built-in light source.
AB  - Manganese deficiency results in neurological and skeletal defects, together with
      ultrastructural disarrangement of the retina in rats. Wild birds show a range of
      Mn concentrations in their tissues, including the liver, raising the possibility
      of Mn-related disorders in the wild. Electroretinography (ERG) provides a useful
      noninvasive approach to evaluate visual function. This method is especially
      useful in birds, as objective analysis of them is very difficult, while they have
      well-developed vision. In this study, we carried out a convenient and reliable
      ERG recording using a contact lens electrode with a built-in light source (LED
      electrode) of Japanese quail (Coturnix coturnix japonica) fed a Mn-deficient
      diet. After 10 min light adaptation, single-flash and flicker cone responses were
      reproducibly recorded to cause an intensity-dependent increase in amplitude of
      both a-wave and b-wave in single-flash ERG. Mn-deficient feeding markedly
      decreased the Mn concentration in the liver by almost half in 3 to 6 weeks,
      followed by body weight loss in 13 to 15 weeks. Implicit time of a-wave and b
      wave cone response by single-flash stimulation was significantly delayed in quail
      with a Mn depletion from 3 to 6 weeks. Every cone response of the Mn-deprived
      quail had a tendency to decrease amplitude. The ultrastructure of cone
      photoreceptor cells was disorganized by Mn deficiency, including changes in outer
      segment discs of photoreceptor cells. These results suggest the essential role of
      Mn in the integrity of the retinal function of birds.

PMID- 18319574
TI  - Effect of repeated stress in early childhood on the onset of diabetes mellitus in
      male Spontaneously Diabetic Torii rats.
AB  - Spontaneously Diabetic Torii (SDT) rats were discovered from SD rats and
      represent a confirmed spontaneous type 2 diabetes mellitus model. We investigated
      the effect of repeated stress in early childhood on SDT rats fed a high-fat diet,
      on locomotor activity and on the onset of diabetes mellitus. Regarding stress, a
      water immersion-restraint stress (WIRS) burden was applied 10 times every other
      day from 4 weeks of age. The results of the study showed, that the locomotor
      activity of the young SDT rats was clearly lower than that of the SD rats, and
      their locomotor activity was inferred to be congenitally low. In addition, the
      stress-burdened SDT rats showed delayed onset of diabetes mellitus and impaired
      glucose tolerance compared with the rats not receiving stress burden. The
      locomotor activity of SDT rats is less than that of SD rats, and they SDT rats
      are thought to have poor at spontaneous energy expenditure. On the other hand,
      the feeding efficiency of the WIRS-burdened SDT rats was reduced, and in
      comparison with the SDT rats with no WIRS burden, energy expenditure was
      increased; this is suggested to influence the onset of diabetes mellitus.

PMID- 18319575
TI  - Changes in peripheral blood mononuclear cells after calving in lactating cows
      with serious decrease of body weight before and after calving.
AB  - The aim of this study was to clarify the hormonal and immunological changes in
      periparturient dairy cows with excessive weight loss following calving. We
      analyzed leukocyte populations and the peripheral blood mononuclear cell (PBMC)
      mRNA of IFN-gamma, IL-4, growth hormone (GH)-receptor (R) and insulin -R and
      measured the GH and insulin concentrations. Ten dairy cows fed in one herd were
      used in this study and were divided into two groups. Five cows that experienced
      loss of body weight following calving of over 10% comprised the Weight Loss
      Group, and the remaining five cows, which experienced loss of body weight of 5%
      or less following calving, served as the Control Group. The Weight Loss Group had
      high serum cholesterol and low blood urea nitrogen levels compared with the
      Control Group throughout the period of observation. In regard to the leukocyte
      populations, there were significantly fewer CD4(+)CD45R-T cells in the Weight
      Loss Group 1 to 2 months after calving compared with the Control Group. The
      percentage of IFN-gamma/IL-4 among PBMCs in the Weight Loss Group tended to be
      lower than in the Control Group throughout the observation period. In the Weight
      Loss Group, the levels of GH-R during month 2 were lower than in the Control
      Group. We concluded that excessive loss of body weight in dairy cows following
      calving is associated with depressed cellular immune function.

PMID- 18319576
TI  - Conformational change in hamster scrapie prion protein (PrP27-30) associated with
      proteinase K resistance and prion infectivity.
AB  - The scrapie prion protein (PrP27-30) is a crucial component of the prion and is
      responsible for its transmissibility. Structural information on this protein is
      limited because it is insoluble and shows aggregated properties. In this study,
      PrP27-30 was effectively dispersed using sonication under the weak alkaline
      condition. Subsequently, the small PrP27-30 aggregates were subjected to
      different pH, heat, and denaturing conditions. The loss of proteinase K (PK)
      resistance of PrP27-30 and prion infectivity were monitored along with
      spectroscopic changes. Prion inactivation could not be achieved by the loss of PK
      resistance alone; a significant loss of the PrP27-30 amyloid structure, which was
      represented by a decrease in thioflavin T fluorescence, was required for the loss
      of transmissibility.

PMID- 18319577
TI  - Prevention of biofilm formation with a coating of 2-methacryloyloxyethyl
      phosphorylcholine polymer.
AB  - Device-associated infections are serious complications, and their prevention is
      an issue of considerable importance. Since biofilms are responsible for these
      refractory infections, effective methods to inhibit biofilm formation are
      required. In this investigation, stainless steel plates with and without 2
      methacryloyloxyethyl phosphorylcholine (MPC) polymer, i.e., poly (MPC-co-n-butyl
      methacrylate) (PMB) coating, were incubated in a medium containing bacteria. In
      the course of incubation, half of the specimens received antibiotics. The
      specimens were stained for nucleic acid and polysaccharides, and then examined
      with a confocal laser scanning microscope. The numbers of bacteria on the
      specimen surfaces were evaluated by an ATP assay. On the surfaces of the
      specimens without PMB coating, the formation of a biofilm enveloping bacteria was
      confirmed. The addition of antibiotics did not effectively decrease the number of
      bacteria. On the other hand, on the surfaces of the specimens with PMB coating,
      no biofilm formation was observed, and the number of bacteria was significantly
      decreased. The addition of potent antibiotics further decreased the number of
      bacteria by 1/100 to 1/1000 times. The PMB coating combined with the validated
      use of antibiotics might provide a method for the simultaneous achievement of
      biocompatible surfaces of devices and the prevention of device-associated
      infections.

PMID- 18319578
TI  - Efficacy and safety of ultrasound-guided percutaneous biopsy of the right kidney
      in cattle.
AB  - The purpose of the present study was to develop a technique for biopsy of the
      kidneys of cattle and to evaluate its usefulness and safety based on 25
      consecutive biopsies. Using a handheld 14G spinal biopsy needle, the right kidney
      was biopsied under ultrasound control by one operator. To assess the immediate
      effects of renal biopsy, twenty cattle were necropsied shortly after the
      procedure and examined. The remaining five animals were biopsied and examined
      daily for nine days and then necropsied. One pass was made for biopsy of the
      right kidney. No immediate or delayed macroscopic hematuria was observed post
      biopsy. Six animals had a thin subcapsular hematoma (less than 2 cm in diameter).
      We conclude that percutaneous ultrasound-guided biopsy of the right kidney is
      safe, fast, cost-effective and practical as long as it is performed properly.

PMID- 18319579
TI  - Characterization of canine platelet activation induced by platelet activating
      factor (PAF).
AB  - Characteristics of the signal transduction in Platelet activating factor (PAF)
      activated platelets and effects of anti-platelet agents on this response were
      investigated in vitro for potential therapeutic applications in canine
      endotoxemia. Blockade of the PAF receptor by a specific blocker has the strongest
      inhibitive effect on the PAF-induced platelet reactions. The response was also
      inhibited by either Ca(2+) channel blockers or prostaglandin E(1).

PMID- 18319580
TI  - Changes in peripheral lymphocyte subsets in the type 1 diabetic dogs treated with
      insulin injections.
AB  - Plasma metabolites and peripheral lymphocyte subsets were measured in ten
      diabetic and ten control dogs to investigate their significances as indicators to
      evaluate immune states in the diabetic dogs. Diabetic dogs were treated with
      insulin injections, however their plasma glucose and fructosamine concentrations
      were significantly higher than those of the controls. There were no significant
      differences in counts of total white blood cells (WBC) and lymphocyte CD8(+)
      cells (cytotoxic T cells) between the control and the diabetic dogs. In the
      diabetic dogs, the counts of CD3(+) (T cells), CD4(+) (Helper T cells) and
      CD21(+) (B cells) cells and the peripheral lymphocytes CD4/CD8 ratio were
      significantly lower than those in the control dogs. We confirmed abnormality of
      lymphocyte subsets in insulin treated diabetic dogs and it may relate to
      depression of immunocompetence and high susceptibility to common infectious
      diseases.

PMID- 18319581
TI  - Evaluation of antigen detection kits for diagnosis of equine influenza.
AB  - In this study, we evaluated whether five rapid antigen detection kits for human
      influenza could be used for the diagnosis of equine influenza (EI). Limiting
      dilution analyses showed that Directigen Flu A+B and ESPLINE INFLUENZA A&B-N had
      the highest sensitivities to equine-2 influenza viruses (EIVs) among the kits
      investigated. From the results of virus detection in nasal swabs taken from
      horses infected with EIV, these two kits could produce positive results in
      reasonable agreement with those obtained by virus isolation or RT-PCR, suggesting
      that these kits could be useful for rapid diagnosis of EI in the field. However,
      from the viewpoint of specificity for EIV, Espline seems to be superior to
      Directigen.

PMID- 18319582
TI  - Effects of mycotoxins on mitogen-stimulated proliferation of bovine peripheral
      blood mononuclear cells.
AB  - The effects of mycotoxins on mitogen-stimulated proliferation of bovine
      peripheral blood mononuclear cells (PBMCs) were investigated. Aflatoxin B(1)
      (AFB(1)), deoxynivalenol (DON) and zearalenone (ZEN) were added to cultures of
      PBMCs, and the proliferation responses were measured using MTT bioassays.
      Suppression of the proliferation of calf PBMCs by AFB(1) and DON was
      significantly stronger than that of cow PBMCs, whereas there were no differences
      in suppressive effects on PBMCs from Holstein and Japanese Black calves and cows.
      The suppressive effect was greatest in the order of DON, AFB(1) and ZEN, and the
      effects of DON and AFB(1) seemed to be dose-dependent. The results suggest that
      some mycotoxins directly suppress proliferation of bovine PBMCs.

PMID- 18319583
TI  - Cytokine responses in camels (Camelus bactrianus) vaccinated with Brucella
      abortus strain 19 vaccine.
AB  - In the present study, we determined the levels of cytokines produced by camel
      (Camelus bactrianus) peripheral blood mononuclear cells (PBMCs) in response to
      live attenuated Brucella abortus (B. abortus) S19 vaccine. Seven camels were
      vaccinated with commercial B. abortus S19 vaccine, and their cytokine responses
      were determined using a real-time PCR assay. Cytokine responses to B. abortus S19
      were examined at 6 hr, 48 hr and 1, 2 and 3 weeks post-vaccination. Serological
      tests were performed to further confirm these immune responses. The results
      revealed that IFN-gamma and IL-6 were upregulated during the first week post
      vaccination. Low level expressions of IL-1alpha, IL-1beta, TNFalpha and IL-10 and
      no expression of IL-2 and IL-4 were observed compared with the control camels.
      The findings showed that B. abortus stimulates cell-mediated immunity by directly
      activating camel Th1 cells to secrete IFN-gamma. This quantification of cytokine
      expression in camels is essential for understanding of Camelidae disease
      development and protective immune responses. This is the first report of in vivo
      camel cytokine quantification after vaccination.

PMID- 18319584
TI  - Plasmodium (Bennettinia) juxtanucleare infection in a captive white eared
      pheasant (Crossoptilon crossoptilon) at a Japanese zoo.
AB  - An adult male white eared-pheasant (Crossoptilon crossoptilon) at a Japanese zoo
      exhibited lethargy and emaciation. Microscopic examination of a blood smear
      revealed a haemosporidian parasitic infection. Based on the morphological
      characteristics and molecular analysis of the parasite, it was identified as
      Plasmodium (Bennettinia) juxtanucleare. This is the first report of P.
      juxtanucleare infection in bird species belonging to the genus Crossoptilon.
      Caution against avian malaria infection is required for the conservation of
      endangered bird species in zoos.

PMID- 18319585
TI  - Cough efficacy is related to the disability status in patients with multiple
      sclerosis.
AB  - BACKGROUND: Cough is an important defense mechanism, whose main function is to
      remove mucus and/or foreign bodies from the airways. In patients with multiple
      sclerosis (MS), respiratory muscle function may be affected and cough may be
      impaired. OBJECTIVES: Respiratory muscle strength and voluntary cough efficacy
      were determined in MS patients and controls, and the relationship between cough
      efficacy and patients' degree of disability was investigated. METHODS: We
      recruited 27 MS patients (age: 41 +/- 11 years; 18 females) with mild-to-moderate
      disability, Expanded Disability Status Scale (EDSS) score range: 1-7, and 20
      healthy controls (age: 37 +/- 11 years; 12 females). The maximal inspiratory
      (PIMAX) and expiratory (PEMAX) pressures, maximal whistle mouth pressures (PMOW),
      cough peak flows (CPF), cough expiratory volumes (CEV) and cough gastric
      pressures (PGA) were measured in all subjects. RESULTS: In MS patients, the EDSS
      score was significantly related to CPF, PEMAX, PMOW, cough PGA, PIMAX and CEV (p
      < 0.01, each correlation). The receiver-operating characteristic curve showed
      that an EDSS score > or =5.5 was consistent with impaired cough (CPF < or =5.6
      l/s), with a sensitivity of 0.85 and a specificity of 0.95 (area under curve
      0.90, p < 0.001). CPF was related to and predicted by PEMAX, PMOW, cough PGA and
      PIMAX in MS patients (p < 0.01 each correlation), but not in controls.
      CONCLUSIONS: MS can affect voluntary cough efficacy and respiratory muscle
      strength, which are inversely related to the patients' degree of disability. In
      addition, this study shows that CPF is a measure of clinical relevance in MS
      patients.

PMID- 18319586
TI  - Inhaled corticosteroids as additional treatment in alpha-1-antitrypsin-deficiency
      related COPD.
AB  - BACKGROUND: No consistent data are available regarding the effect of inhaled
      corticosteroids (ICS) in alpha(1)-antitrypsin-deficiency (AATD)-related COPD.
      Recent data report inflammatory effects of the polymers of alpha(1)-antitrypsin
      on the peripheral lung. OBJECTIVES: The aim of this study was to assess the
      effectiveness of an extra-fine ICS, hydrofluoroalkane-134a beclometasone
      dipropionate (HFA-BDP) with a mass median aerodynamic diameter of 1.1 microm, on
      lung function and exercise tolerance in COPD patients with AATD when added to
      long-acting bronchodilators (LABAs). METHODS: After a 1-week washout, 8 steroid
      naive COPD patients with AATD (ZZ genotype), within a double-blind randomized
      cross-over study, were assigned to one of the following 16-week treatments: (1)
      HFA-BDP 400 microg b.i.d., salmeterol 50 microg b.i.d. and oxitropium bromide 200
      microg t.i.d. or (2) placebo, salmeterol 50 microg b.i.d. and oxitropium bromide
      200 microg t.i.d; after a 2-week washout period they received the other
      treatment. In weeks 1, 17, 19 and 35, patients took a spirometry assessment
      (breathing air and heliox) and a shuttle walking test (SWT) with dyspnea assessed
      by the modified Borg scale. RESULTS: Significant differences in improvement were
      found in FEV(1), FVC, IC, distance covered and dyspnea perceived during SWT
      between the 2 treatments and baseline values (p < 0.05; Friedman's test).
      However, further analysis showed that only the LABAs + ICS condition showed
      significant increases in the FEV(1), FVC, IC, DeltaMEF(50%) and distance covered
      during SWT along with a reduction in maximum isostep exertional dyspnea (p <
      0.05; Wilcoxon test). A greater distance was walked at the end of the SWT with
      LABA + ICS than LABAs alone (301 +/- 105 vs. 270 +/- 112 m; p < 0.05).
      CONCLUSIONS: In AATD-related COPD patients (ZZ genotype) the addition of extra
      fine ICS to LABAs decreases airway narrowing, mostly in the small airways,
      further reducing dynamic hyperinflation with a marked improvement in exercise
      tolerance and dyspnea, suggesting that a peripheral inflammatory process
      contributes to airflow obstruction in these patients.

PMID- 18319587
TI  - Effect of meal replacement on metabolic risk factors in overweight and obese
      subjects.
AB  - AIM: Our objective was to assess alterations in metabolic risk factors, body
      weight, fat mass and hormonal parameters following 6 weeks of lifestyle
      intervention with increased physical activity and either a meal-replacement
      regimen or a low calorie diet. RESEARCH METHODS AND PROCEDURES: 90 overweight or
      obese subjects (age 47 +/- 7.5 years, weight 90.6 +/- 11.3 kg, BMI 31.5 +/- 2.3)
      were included in this randomized controlled clinical trial. Subjects in the fat
      restricted low-calorie-diet group (LCD-G; n = 30) received 2 dietary counseling
      sessions and instructions on how to increase physical activity. Subjects in the
      meal-replacement-diet group (MRD-G; n = 60) received the same lifestyle education
      and were instructed to replace 2 daily meals by a low-calorie high soy-protein
      drink. RESULTS: Subjects in the MRD-G lost significantly more weight (6.4 vs. 3.1
      kg, p < 0.01) and fat mass (5.1 vs. 2.8 kg, p < 0.01) than the LCD-G. Most
      metabolic risk parameters were reduced in both the MRD-G and the LCD-G; however,
      subjects in the MRD-G showed a higher reduction in waist circumference (6.1 vs.
      1.8 cm, p < 0.01) and a larger decrease in triglycerides (-19.6 vs. +12.5 mg/dl,
      p < 0.01). The prevalence of the metabolic syndrome was reduced in subjects in
      the MRD-G only (-12%, p < 0.05) compared to an unchanged risk score in the LCD-G.
      The reductions in leptin (18.2 vs. 6.97 ng/ml) and insulin (4.92 vs. 0.58
      microU/ml) were only significant in the MRD-G (p < 0.01). DISCUSSION: Our data
      suggest that even over a short period of time, a meal-replacement diet is more
      effective in reducing metabolic risk factors, insulin, and leptin, and in
      improving anthropometric measures than a fat-restricted low-calorie diet.

PMID- 18319588
TI  - Circannual rhythm of laboratory test parameters among chronic haemodialysis
      patients.
AB  - BACKGROUND/AIMS: Seasonal variations in laboratory test results have been pointed
      out in dialysis patients. Although the mechanism for this phenomenon is not
      clear, this could result in changes in dialysis and medication prescriptions. We
      investigated the effect of the circannual rhythm on laboratory test parameters in
      chronic haemodialysis patients. METHODS: Data of 38 laboratory test parameters
      were collected every month and analyzed for 150 stable haemodialysis patients,
      with non-linear sine wave regression and paired t test between data of peak and
      trough months. RESULTS: Serum urea nitrogen, unsaturated iron binding capacity,
      lactate dehydrogenase, alkaline phosphatase, amylase, and neutrophil count showed
      significant circannual rhythms with high amplitudes. Additionally, serum
      creatinine, uric acid, chloride, calcium, phosphate, magnesium, total
      cholesterol, total protein, leucocyte count, mean corpuscular haemoglobin level,
      mean corpuscular haemoglobin concentration, and platelet count showed significant
      circannual rhythms with little amplitudes. CONCLUSIONS: The circannual rhythm of
      laboratory test parameters could be attributed to seasonal variations in food
      intake. Awareness of these variations should be taken into account in the
      interpretation of laboratory results.

PMID- 18319589
TI  - Prospective study of the association between fluoride intake and dental fluorosis
      in permanent teeth.
AB  - OBJECTIVE: To evaluate the relationship between fluoride intake and dental
      fluorosis in permanent central incisors and first molars. METHODS: Fluoride
      intake (mg F/kg body weight/day) from diet, dentifrice and both combined was
      determined on a single occasion in 1998 among children aged 19-39 months living
      in two fluoridated Brazilian communities (0.6-0.8 ppm F). Six years later, when
      the permanent teeth of these children had erupted (central incisors and first
      molars), 49 children aged 7-9 years [20 girls (40.8%) and 29 boys (58.2%)] were
      evaluated for dental fluorosis. To test the association between fluorosis and
      fluoride intake, children were dichotomized into two groups, cases (children with
      dental fluorosis on at least two teeth, TFI > or =1) and noncases (children
      without dental fluorosis, TFI = 0). RESULTS: Among the case group (n = 29),
      median fluoride doses from diet, dentifrice and combined were 0.031, 0.050 and
      0.083 mg F/kg/day, respectively. Among the noncase group (n = 20), median
      fluoride doses were 0.029, 0.049, 0.084 mg F/kg/day, respectively. There was no
      association between dental fluorosis in permanent teeth and fluoride intake from
      diet, dentifrice and combined (p > 0.05). CONCLUSIONS: There was no difference
      between children with and without fluorosis in the permanent central incisors and
      first molars regarding fluoride intake. However, this study has limitations that
      must be recognized: fluoride intake was only measured once, and there were no
      children in the sample with severe degrees of dental fluorosis.

PMID- 18319590
TI  - 14-3-3 zeta and tau genes interactively decrease Alzheimer's disease risk.
AB  - Abnormal tau hyperphosphorylation has been suggested as being one of the central
      events in the development of neurofibrillary tangles, which are one of the
      characteristic neuropathological lesions found in Alzheimer's disease (AD)
      brains. 14-3-3 zeta protein is associated with tau in brain and stimulates tau
      phosphorylation. In a case-control study in 293 AD patients and 396 healthy
      controls, we examined whether the combined gene effects between 14-3-3 zeta
      (intron 4, rs 983583) polymorphism and tau (intron 9, rs 2471738) polymorphism
      might be responsible for susceptibility to AD. Subjects carrying both the 14-3-3
      zeta (intron 4, rs 983583) AA and the tau (intron 9, rs 2471738) CC genotypes had
      a two and a half times lower risk of developing AD than subjects without these
      risk genotypes (OR = 0.4, 95% CI = 0.2-0.8, p = 0.016). Considering synergistic
      effects between polymorphisms in tau phosphorylation related genes may help in
      determining the risk profile for AD.

PMID- 18319591
TI  - The Severe Cognitive Impairment Rating Scale--an instrument for the assessment of
      cognition in moderate to severe dementia patients.
AB  - BACKGROUND/AIMS: This study aimed to develop a brief, reliable and valid test for
      cognitive function of severely demented patients. METHODS: We constructed the
      Severe Cognitive Impairment Rating Scale, which consisted of 11 items covering
      memory, language, visuospatial function, frontal function and orientation, and
      investigated its reliability and validity on 267 subjects [normal: 65, very mild
      Alzheimer's disease (AD): 42, mild AD: 58, moderate AD: 36, severe AD: 44,
      profound AD: 22]. RESULTS: The internal consistency obtained by Cronbach's
      coefficient alpha was 0.93. The interrater reliability and test-retest
      reliability in the moderately to severely impaired subjects with an MMSE score of
      <or=14 was 0.99 (p < 0.001) and 0.90 (p < 0.001), respectively. It showed
      significant correlation with Severe MMSE (r = 0.96, p < 0.01), MMSE (r = 0.86, p
      < 0.01) and Clinical Dementia Rating (r = -0.83, p < 0.01). It was robust to both
      the floor effect in the severe/profound stage of AD and the ceiling effect in the
      mild/moderate stage of AD. Exploratory factor analysis yielded 2 factors
      (automatic informational processing and controlled informational processing)
      accounting for 73.5% of the total variance. CONCLUSIONS: The Severe Cognitive
      Impairment Rating Scale is a valid and reliable test for evaluating the cognitive
      function of advanced AD patients.

PMID- 18319592
TI  - mTOR inhibitors and calcineurin inhibitors do not affect adhesion molecule
      expression of human macro- and microvascular endothelial cells.
AB  - We examined the effect of cyclosporin A, tacrolimus, sirolimus and everolimus on
      the cell growth, viability, proliferation, expression of cellular adhesion
      molecules (CAM) and leukocyte (PBMC) binding of human macrovascular (coronary
      artery, saphenous vein) and microvascular endothelial cells (EC). Tacrolimus did
      not affect EC integrity, growth or expression of CAM. Exclusively, EC from the
      coronary arteries showed a reduced cellular growth (about 30%) under cyclosporin
      A and tacrolimus treatment. In contrast, treatment with mTOR inhibitors reduced
      EC proliferative activity by about 40%, independently of the EC origin. No
      induction of apoptosis (caspase-3/7 activity) or cytotoxicity (MTS test) was
      observed. Long-term treatment with high concentrations of sirolimus and
      everolimus did not enhance the expression of CAM. Stimulation with tumor necrosis
      factor significantly increased the expression of CAM, independently of the drugs
      used. None of the mTOR inhibitors influenced the tumor necrosis factor-induced
      expression of CAM, whereas adhesion of PBMC increased significantly, as described
      by other papers. In summary, neither calcineurin inhibitors nor mTOR inhibitors
      activate human micro- and macrovascular EC. Therefore, the investigated drugs are
      unlikely to contribute to EC activation during transplant-associated
      vasculopathy.

PMID- 18319593
TI  - Gene expression during the development of experimentally induced cerebral
      aneurysms.
AB  - Cerebral aneurysms are a major cause of subarachnoid hemorrhage, but the
      mechanism of their development remains unclear. In this study, we investigated
      candidate genes whose expression is significantly changed during the development
      of experimentally induced cerebral aneurysms using adaptor-tagged competitive
      polymerase chain reaction (ATAC-PCR). Twenty-four rats received sham operation
      (control) or the operation for the induction of experimental cerebral aneurysms.
      Rats were sacrificed at time 0, 2 weeks, 1 month and 3 months after the operation
      (n = 6 for each group). RNAs from right anterior cerebral artery/olfactory artery
      (ACA/OA) bifurcations were assessed via a 191-gene data matrix expression profile
      by ATAC-PCR. We identified 15 genes whose expression is significantly altered
      during cerebral aneurysm formation, including major heparan sulfate proteoglycan,
      cathepsin B, hevin and beta(4)-integrin. We also confirmed protein expression of
      beta(4)-integrin in rat cerebral aneurysms by quantitative real-time PCR and
      immunohistochemistry. The ATAC-PCR revealed temporal changes in gene expression
      during the development of experimental cerebral aneurysms. The genes that were
      significantly changed in this study would be the candidates for future studies
      concerning the development of cerebral aneurysms.

PMID- 18319594
TI  - Testosterone and blood pressure regulation.
AB  - BACKGROUND: There is substantial evidence that androgens may play a role in
      determining sex-specific blood pressure. Men are at higher risk for developing
      coronary heart disease or hypertension compared to premenopausal women. However,
      effects of androgens on the renal and cardiovascular system are complex. This
      review provides a critical overview of testosterone actions. METHODS: We searched
      Pubmed library for experimental, animal and clinical studies, using the keywords
      'blood pressure', 'hypertension', 'testosterone' and 'androgens'. RESULTS: While
      acute administration of testosterone seems to decrease vascular tone, the long
      term net effect of androgens appears to be vasoconstriction via upregulation of
      thromboxane A2 expression, norepinephrine synthesis, angiotensin II expression,
      and endothelin-1 action. Furthermore, androgens cause cardiac hypertrophy,
      promote atherosclerosis, vascular remodelling and stimulate renal prohypertensive
      processes involving the renin-angiotensin-aldosterone system. Androgens seem to
      promote oxidative stress in the kidney and may also play a role in the
      differentiation of brain areas involved in blood pressure regulation. CONCLUSION:
      The effects of sex steroids on different parts of the renal-vascular system are
      complex and often contradictory. In sum, net effects of androgen action seem to
      be vasoconstriction, atherosclerosis and stimulation of the renin-angiotensin
      aldosterone system. Therefore, androgens may determine blood pressure and the
      prevalence of cardiovascular disease.

PMID- 18319595
TI  - Gonadal steroids regulate neural plasticity in the sexually dimorphic nucleus of
      the preoptic area of adult male and female rats.
AB  - BACKGROUND: The densely staining sexually dimorphic nucleus of the preoptic area
      (SDNPOA) is profoundly affected by gonadal steroids during perinatal development.
      METHODS: We tested whether the SDNPOA in rats also remains responsive to gonadal
      hormones in adulthood. RESULTS: Castration of 60-day-old male rats led to a
      reduction of soma size in SDNPOA neurons 28 days later, but not 14 days later. In
      contrast, the SDNPOA volume in males was unaffected by adult castration,
      increasing somewhat between 60 and 88 days of age in both castrated males and
      sham controls. For female rats ovariectomized at 60 days of age, testosterone
      treatment resulted in a significantly larger SDNPOA soma size after either 14 or
      28 days of treatment, compared to blank-treated controls. Testosterone-treated
      ovariectomized females also had a modestly larger SDNPOA volume after 28 days,
      but not 14 days, of treatment compared to blank-treated ovariectomized animals. A
      second experiment revealed that these effects in females were due to ovariectomy:
      both SDNPOA soma size and regional volume shrank in females that were
      ovariectomized compared to females subjected to sham surgery. The effects of
      ovariectomy were blocked by testosterone treatment. The cessation of testosterone
      treatment in females returned SDNPOA soma size and regional volume to that of
      control-treated ovariectomized females. CONCLUSION: These results indicate
      considerable plasticity of the adult rat SDNPOA, and that (1) circulating
      androgens are required to maintain soma size, but not regional volume in males,
      and (2) ovarian steroids maintain both soma size and regional volume of the
      SDNPOA in females, an effect that can be mimicked with testosterone treatment and
      is fully reversible in adulthood.

PMID- 18319596
TI  - p75 and TrkC neurotrophin receptors demonstrate a different immunoreactivity
      profile in comparison to TrkA and TrkB receptors in human normal pituitary gland
      and adenomas.
AB  - BACKGROUND/AIMS: Recent knowledge indicates that neurotrophins play a significant
      role in neuroendocrine systems through their specific receptors TrkA, TrkB, TrkC
      and low-affinity p75(NTR) receptor. TrkA and TrkB receptors have been previously
      detected in numerous endocrine cells in human anterior pituitary and adenomas. In
      the present study, the localization of p75(NTR) and TrkC along with TrkA and TrkB
      receptors was investigated. METHODS: Semi-serial paraffin-embedded sections of 5
      human normal pituitaries and 30 adenomas were immunostained using specific
      antibodies. RESULTS: Expression of p75(NTR) receptor was demonstrated in the
      intricate capillary and reticulin network in the anterior pituitary and in the
      pericapillary tissue and pituicytes in the posterior lobe. p75(NTR)
      immunoreactivity was absent from all adenomas. In normal anterior pituitary, a
      few scattered cells showed weak TrkC immunoreactivity in contrast to a high
      percentage of endocrine cells distributed throughout the pars distalis and pars
      intermedia which exhibited strong TrkA and/or intermediate TrkB immunoreactivity.
      Double immunohistochemistry demonstrated TrkA immunoreactivity in more than 80%
      of lactotropes and 70% of corticotropes and to a lesser extent in other cell
      types. Furthermore, in the majority of adenomas, independently of type, sex and
      age, a high percentage of TrkA- and/or TrkB-positive cells was detected.
      Interestingly, TrkC expression appeared to be increased in some adenomas compared
      to normal pituitary. Endothelial cells and perivascular connective tissue were
      always TrkB-immunostained. CONCLUSION: The above findings support a potential
      role of all neurotrophins, through their different receptors, in pituitary
      functions.

PMID- 18319597
TI  - Heparin cryoprecipitation reduces plasma levels of non-traditional risk factors
      for atherosclerosis in vitro.
AB  - AIMS: To show that heparin cryoprecipitation (HCP), an in vitro method of plasma
      purification, reduces the levels of in vivo modified proteins and non-traditional
      risk factors from plasma of atherosclerotic hemodialysis (HD) patients. METHODS:
      HCP was applied to plasma obtained from HD patients and controls, forming a
      precipitate--cryogel. Levels of fibrinogen, albumin, CRP, TNF-alpha, IL-6,
      advanced oxidation protein products, carbonylated fibrinogen and carbonylated
      albumin were determined in plasma before and after applying HCP and in the
      cryogel. RESULTS: Treatment of HD plasma with HCP, beyond the significant
      reduction of the increased levels of all the above-mentioned molecules, reduced
      fibrinogen, TNF-alpha, carbonylated fibrinogen and carbonylated albumin to
      control levels which were simultaneously found in the cryogel. CONCLUSIONS: HCP
      applied to plasma enables the simultaneous precipitation of modified molecules
      and circulating non-traditional risk factors for atherosclerosis. This study may
      serve as a base for the future development of a clinical purification technique.

PMID- 18319598
TI  - Voxel-based analysis of gray matter and CSF space in idiopathic normal pressure
      hydrocephalus.
AB  - AIMS: To investigate regional morphologic changes in idiopathic normal pressure
      hydrocephalus (INPH) based on diagnosis with INPH Guidelines using voxel-based
      morphometry. METHOD: Three-dimensional magnetic resonance imaging was performed
      in 34 INPH patients, who met probable INPH criteria, probable 34 Alzheimer
      disease patients, and 34 normal control subjects. RESULTS: Statistical parametric
      mapping was used to conduct voxel-based morphometry analysis of the morphologic
      data and revealed enlarged ventricles and sylvian fissures and stenotic sulci of
      high convexity, especially in the precuneus in the INPH group, with decreased
      gray matter density in the insula, caudate and thalamus. CONCLUSION: In INPH,
      morphologic change occurs in the frontoparietal high convexity with ventricular
      dilatations, dilated sylvian fissures and tight sulci in the medial parietal
      lobes.

PMID- 18319599
TI  - Depressive symptoms, vascular risk factors and mild cognitive impairment. The
      Italian longitudinal study on aging.
AB  - AIMS: We evaluated the impact of depressive symptoms on the rate of incident mild
      cognitive impairment (MCI) after a 3.5-year follow-up, and we assessed the
      interaction between depressive symptoms and vascular risk factors for incident
      MCI. METHODS: A total of 2,963 individuals from a sample of 5,632 65- to 84-year
      old subjects were cognitively and functionally evaluated at the 1st and 2nd
      surveys of the Italian Longitudinal Study on Aging, a prospective cohort study
      with a 3.5-year follow-up. MCI and dementia were classified using current
      clinical criteria. Depressive symptoms were measured with the Geriatric
      Depression Scale. RESULTS: Among the 2,963 participants, 139 prevalent MCI cases
      were diagnosed at the 1st survey. During the 3.5-year follow-up, 105 new events
      of MCI were diagnosed. We did not observe any significant association between
      depressive symptoms and incident MCI (RR = 1.25, 95% CI = 0.85-1.84, chi(2) =
      1.30, p < 0.25). No sociodemographic variables or vascular risk factors modified
      the relationship between depressive symptoms and incident MCI. CONCLUSION: In our
      population, depressive symptoms were not associated with the rate of incident
      MCI. Our findings did not support a role of sociodemographic variables or
      vascular risk factors in the link between depressive symptoms and incident MCI.

PMID- 18319600
TI  - Neuroanatomical correlates of unawareness of memory deficits in early Alzheimer's
      disease.
AB  - BACKGROUND/AIMS: To investigate neuroanatomical substrates of unawareness of
      memory deficits in patients with early Alzheimer's disease (AD). METHODS: We
      compared regional perfusion deficits between AD patients with awareness (n = 19)
      and unawareness (n = 19). SPECT data were analyzed by statistical brain imaging
      method. RESULTS: Statistical maps demonstrated a more extensive and severe
      reduction in perfusion in the unaware group than in the aware group. Quantitative
      analysis demonstrated a significant difference between the groups in the right
      subcallosal, anterior cingulate and cingulate gyri and left orbital, subcallosal,
      and anterior cingulate gyri. CONCLUSION: Functional damage to the inferior,
      medial and orbital frontal lobes as well as the anterior cingulate gyri may be
      associated with the lack of awareness in patients with early AD.

PMID- 18319601
TI  - Disease severity, quality of life and health care in plaque-type psoriasis: a
      multicenter cross-sectional study in Germany.
AB  - BACKGROUND: Plaque-type psoriasis produces significant morbidity, has negative
      effects on patients' health-related quality of life (HRQoL), and represents an
      economic burden. OBJECTIVES: The assessment of disease severity, HRQoL and health
      care in plaque-type psoriasis in everyday German medical practice. METHODS:
      Details of patients with plaque-type psoriasis were recorded by 48 dermatologists
      in Germany. During the visit, demographic data, medical history, previous and
      current treatments, occupational impairment, the current state of the disease
      (measured by the Psoriasis Area and Severity Index; PASI), overall lesion
      severity, and HRQoL were evaluated. RESULTS: In total, 1,511 plaque-type
      psoriasis patients were included. The average PASI score was 12.0. The average
      Dermatology Life Quality Index score was 8.6. Among the patients with the
      severest psoriasis (PASI >20), only 45.4% had ever been prescribed systemic
      treatments. CONCLUSIONS: Psoriasis patients have a reduced HRQoL and are not
      sufficiently treated in practice. A more widespread use of systemic treatment and
      the definition of treatment goals are essential to improve the standard of care
      for psoriasis patients.

PMID- 18319602
TI  - Comparison of effects of total enteral versus total parenteral nutrition on
      ischemia/reperfusion-induced heart injury in rats.
AB  - BACKGROUND: The long-term effect of nutrition on cardiac function remains to be
      elucidated. One possible link is the newly discovered gastric hormone ghrelin,
      which has been reported to be cardioprotective. AIM: The present study examined
      whether total enteral nutrition (TEN) and total parenteral nutrition (TPN) differ
      in their modulation of ghrelin production and their effects on cardiac function
      after ischemia/reperfusion injury. METHODS: Rats received isocaloric parenteral
      or enteral nutrition through implanted vascular catheters or gastrostomy tubes.
      TEN was administered in a conventional (TEN-C) or immunonutrition (TEN-I) form.
      After 7 days, serum ghrelin levels were determined by enzyme-linked immunosorbent
      assays and myocardial function was assessed using the Langendorff isolated heart
      technique. RESULTS: TEN-I animals had significantly higher plasma ghrelin levels
      than the other groups. After ischemia/reperfusion injury, left ventricular
      developed pressure decreased in animals receiving TPN when compared to animals
      receiving TEN-I. Animals receiving TPN also had significant reductions in their
      maximal rates of increase and decrease in left ventricular pressure when compared
      to animals receiving TEN-I (unpaired t test, p < 0.05). CONCLUSION: TEN-I
      increases serum levels of ghrelin, which protects cardiac function after
      ischemic/reperfusion injury. Because TEN-I more effectively protects cardiac
      function, we recommend it for long-term nutritional support.

PMID- 18319603
TI  - Progesterone, estrogen and pregnancy do not decrease colon myoelectric activity
      in rats: an in vivo study.
AB  - BACKGROUND: Progesterone, estrogen and the hormonal complex of pregnancy have
      been responsible for some degree of colon hypomotility in human pregnancy.
      OBJECTIVE: To find out if estrogen, progesterone and the hormonal complex of
      pregnancy decrease colon myoelectric activity. METHODS: The study was performed
      in 37 healthy female rats in which electrodes were implanted on the serosa of the
      proximal ascendent, distal ascendent, transverse, and descendent colon. We
      analyzed the records of colon myoelectric activity in vivo in five groups:
      control, ovariectomized, ovariectomized and treated with estrogen, ovariectomized
      and treated with progesterone, and pregnant rats. RESULTS: We found a great
      variation in myoelectric activity in all groups studied. The mean of electric
      activity did not show statistical difference among the five groups, but pregnant
      rats had a statistically significant higher duration of maximum electric activity
      in all distances from the cecocolon junction. CONCLUSION: Pregnant rats had a
      statistically higher duration of maximum electric activity. If we could transpose
      these results to humans, this increase in duration of colon myoelectric activity
      could explain, in part, the slight constipation that some pregnant women have.

PMID- 18319604
TI  - SGK1-dependent upregulation of connective tissue growth factor by angiotensin II.
AB  - Angiotensin II has previously been shown to trigger fibrosis, an effect involving
      connective tissue growth factor (CTGF). The signaling pathways linking
      angiotensin II to CTGF formation are, however, incompletely understood. A gene
      highly expressed in fibrosing tissue is the serum- and glucocorticoid-inducible
      kinase SGK1. The present study explored whether SGK1 is transcriptionally
      regulated by angiotensin II and participates in the angiotensin II-dependent
      regulation of CTGF expression. To this end, experiments have been performed in
      human kidney fibroblasts and mouse lung fibroblasts from gene-targeted mice
      lacking SGK1 (sgk1-/-) and their wild-type littermates (sgk1+/+). In human renal
      fibroblasts, SGK1 and CTGF protein expression were enhanced by angiotensin II (10
      nM) within 4 h. In sgk1+/+ mouse fibroblasts, SGK1 transcript levels were
      significantly increased after 4 h of angiotensin II treatment. Angiotensin II
      stimulated both transcript and protein abundance of CTGF in fibroblasts from
      sgk1+/+ mice, effects significantly blunted in fibroblasts of sgk1-/- mice. In
      conclusion, angiotensin II stimulates the expression of SGK1, which is in turn
      required for the stimulating effect of angiotensin II on the expression of CTGF.
      Thus, SGK1 presumably contributes to the profibrotic effect of angiotensin II.

PMID- 18319605
TI  - Vanadate-induced suicidal erythrocyte death.
AB  - Vanadium, a trace element, as vanadate (VO4(3-)) is known to interfere with a
      wide variety of enzymes including Ca2+ ATPase and Na+/+ ATPase. VO4(3-) is
      excreted mainly via the kidney. In renal insufficiency, the impaired VO4(3-)
      excretion leads to VO4(3-) accumulation in blood.The present study explored the
      effect of VO4(3-) on eryptosis, the suicidal death of erythrocytes. Eryptosis is
      characterized by cell shrinkage and phosphatidylserine exposure at the
      erythrocyte surface. Eryptotic cells are phagocytosed and thus rapidly cleared
      from circulating blood. Stimulators of eryptosis include an increase of the
      cytosolic Ca2+ concentration. Erythrocyte Ca2+ activity was estimated from Fluo-3
      fluorescence, phosphatidylserine exposure from annexin V-binding, and erythrocyte
      volume from forward scatter in FACS analysis. Exposure of erythrocytes to VO4(3-)
      increased cytosolic Ca2+ concentration, enhanced the percentage of annexin V
      binding erythrocytes, decreased erythrocyte forward scatter, and lowered the
      intracellular ATP concentration. In conclusion, VO4(3-) induces eryptosis at
      least partially through increase of cytosolic Ca2+ concentration, an effect
      presumably contributing to the development of anemia in chronic renal failure.

PMID- 18319606
TI  - Hyponatremia revisited: translating physiology to practice.
AB  - The complexity of hyponatremia as a clinical problem is likely caused by the
      opposite scenarios that accompany this electrolyte disorder regarding
      pathophysiology (depletional versus dilutional hyponatremia, high versus low
      vasopressin levels) and therapy (rapid correction to treat cerebral edema versus
      slow correction to prevent osmotic demyelination, fluid restriction versus fluid
      resuscitation). For a balanced differentiation between these opposites, an
      understanding of the pathophysiology of hyponatremia is required. Therefore, in
      this review an attempt is made to translate the physiology of water balance
      regulation to strategies that improve the clinical management of hyponatremia. A
      physiology-based approach to the patient with hyponatremia is presented, first
      addressing the possibility of acute hyponatremia, and then asking if and if so
      why vasopressin is secreted non-osmotically. Additional diagnostic
      recommendations are not to rely too heavily of the assessment of the
      extracellular fluid volume, to regard the syndrome of inappropriate antidiuresis
      as a diagnosis of exclusion, and to rationally investigate the pathophysiology of
      hyponatremia rather than to rely on isolated laboratory values with arbitrary
      cutoff values. The features of the major hyponatremic disorders are discussed,
      including diuretic-induced hyponatremia, adrenal and pituitary insufficiency, the
      syndrome of inappropriate antidiuresis, cerebral salt wasting, and exercise
      associated hyponatremia. The treatment of hyponatremia is reviewed from simple
      saline solutions to the recently introduced vasopressin receptor antagonists,
      including their promises and limitations. Given the persistently high rates of
      hospital-acquired hyponatremia, the importance of improving the management of
      hyponatremia seems both necessary and achievable.

PMID- 18319607
TI  - Editorial.

PMID- 18319608
TI  - Endochondral ossification signals in cartilage degradation during osteoarthritis
      progression in experimental mouse models.
AB  - Osteoarthritis (OA), one of the most common skeletal disorders characterized by
      cartilage degradation and osteophyte formation in joints, is induced by
      accumulated mechanical stress; however, little is known about the underlying
      molecular mechanism. Several experimental OA models in mice by producing
      instability in the knee joints have been developed to apply approaches from mouse
      genetics. Although proteinases like matrix metalloproteinases and aggrecanases
      have now been proven to be the principal initiators of OA progression, clinical
      trials of proteinase inhibitors have not been successful for the treatment,
      turning the interest of researchers to the upstream signals of proteinase
      induction. These signals include undegraded and fragmented matrix proteins like
      type II collagen or fibronection that affects chondrocytes through distinct
      receptors. Another signal is pro-inflammatory factors that are produced by
      chondrocytes and synovial cells; however, recent studies that used mouse OA
      models in knockout mice did not support that these factors have a role in the
      central contribution to OA development. Our mouse genetic approaches found that
      the induction of a transcriptional activator Runx2 in chondrocytes under
      mechanical stress contributes to the pathogenesis of OA through chondrocyte
      hypertrophy. In addition, chondrocyte apoptosis has recently been identified as
      being involved in OA progression. We hereby propose that these endochondral
      ossification signals may be important for the OA progression, suggesting that the
      related molecules can clinically be therapeutic targets of this disease.

PMID- 18319609
TI  - Altered complexin expression in psychiatric and neurological disorders: cause or
      consequence?
AB  - Complexins play a critical role in the control of fast synchronous
      neurotransmitter release. They operate by binding to trimeric SNARE complexes
      consisting of the vesicle protein Synaptobrevin and the plasma membrane proteins
      Syntaxin and SNAP-25, which are key executors of membrane fusion reactions. SNARE
      complex binding by Complexins is thought to stabilize and clamp the SNARE complex
      in a highly fusogenic state, thereby providing a pool of readily releasable
      synaptic vesicles that can be released quickly and synchronously in response to
      an action potential and the concomitant increase in intra-synaptic Ca(2+) levels.
      Genetic elimination of Complexins from mammalian neurons causes a strong
      reduction in evoked neurotransmitter release, and altered Complexin expression
      levels with consequent deficits in synaptic transmission were suggested to
      contribute to the etiology or pathogenesis of schizophrenia, Huntington's
      disease, depression, bipolar disorder, Parkinson's disease, Alzheimer's disease,
      traumatic brain injury, Wernicke's encephalopathy, and fetal alcohol syndrome. In
      the present review I provide a summary of available data on the role of altered
      Complexin expression in brain diseases. On aggregate, the available information
      indicates that altered Complexin expression levels are unlikely to have a causal
      role in the etiology of the disorders that they have been implicated in, but that
      they may contribute to the corresponding symptoms.

PMID- 18319610
TI  - Identification of a third haplotype of the sequence linked to the Restorer-of
      fertility (Rf) gene and its implications for male-sterility phenotypes in peppers
      (Capsicum annuum L.).
AB  - Cytoplasmic male sterility (CMS), one of the most important traits in crop
      breeding, has been used for commercial seed production by F1 hybrid cultivars of
      pepper (Capsicum annuum L.). To develop reliable molecular markers for allelic
      selection of the Restorer-of-fertility (Rf) gene, which is known to be a major
      determinant of pollen fertility restoration in peppers, a sequence of
      approximately 10 kb flanking an RAPD fragment closely linked to the Rf locus was
      obtained by genome walking. A homology search revealed that this sequence
      contained an LTR retrotransposon and a non-LTR LINE-like retrotransposon.
      Sequencing of this Rf-linked region to search for polymorphisms between a
      dominant and recessive allele revealed 98% nucleotide sequence identity between
      them. A third polymorphic haplotype of the Rf-linked sequence, which has 94-96%
      nucleotide sequence identity with the two previously isolated haplotypes, was
      identified among a large number of breeding lines. Utilizing polymorphic
      sequences in the haplotypes, PCR markers were developed for selection of
      particular haplotypes and used to examine the distribution of the haplotypes in
      diverse breeding lines, cultivars, and C. annuum germplasms. Surprisingly, the
      third haplotype was the predominant type in C. annuum germplasms, while its
      frequency in F1 hybrid cultivars was relatively low. Meanwhile, analysis of
      breeding lines whose Rf allele genotypes and male-sterility phenotypes were
      already known revealed that the third haplotype was mainly present in exotic
      breeding lines that cause unstable male-sterility when combined with sterile
      cytoplasms.

PMID- 18319611
TI  - Genetic organization of the hrp genes cluster in Erwinia pyrifoliae and
      characterization of HR active domains in HrpNEp protein by mutational analysis.
AB  - The disease-specific (dsp) region and the hypersensitive response and
      pathogenicity (hrp) genes, including the hrpW, hrpNEp, and hrpC operons have
      previously been sequenced in Erwinia pyrifoliae WT3 [Shrestha et al. (2005a)]. In
      this study, the remaining hrp genes, including the hrpC, hrpA, hrpS, hrpXY, hrpL
      and hrpJ operons, were determined. The hrp genes cluster (ca. 38 kb) was
      comprised of eight transcriptional units and contained nine hrc (hrp conserved)
      genes. The genetic organization of the hrp/hrc genes and their orientation for
      the transcriptions were also similar to and collinear with those of E. amylovora,
      showing > or = 80% homologies. However, ORFU1 and ORFU2 of unknown functions,
      present between the hrpA and hrpS operons of E. amylovora, were absent in E.
      pyrifoliae. To determine the HR active domains, several proteins were prepared
      from truncated fragments of the N-terminal and the C-terminal regions of HrpN(Ep)
      protein of E. pyrifoliae. The proteins prepared from the N-terminal region
      elicited HR, but not from those of the C-terminal region indicating that HR
      active domains are located in only N-terminal region of the HrpN(Ep) protein. Two
      synthetic oligopeptides produced HR on tobacco confirming presence of two HR
      active domains in the HrpN(Ep). The HR positive N-terminal fragment (HN delta
      C187) was further narrowed down by deleting C-terminal amino acids and internal
      amino acids to investigate whether amino acid insertion region have role in
      faster and stronger HR activity in HrpN(Ep) than HrpN(Ea). The HrpN(Ep) mutant
      proteins HN delta C187 (D1AIR), HN delta C187 (D2AIR) and HN delta C187 (DM41)
      retained similar HR activation to that of wild-type HrpN(Ep). However, the
      HrpN(Ep) mutant protein HN delta C187 (D3AIR) lacking third amino acid insertion
      region (102 to 113 aa) reduced HR when compared to that of wild-type HrpN(Ep).
      Reduction in HR elicitation could not be observed when single amino acids at
      different positions were substituted at third amino acids insertion region. But,
      substitution of amino acids at L103R, L106K and L110R showed reduction in HR
      activity on tobacco suggesting their importance in activation of HR faster in the
      HrpN(Ep) although it requires further detailed analysis.

PMID- 18319612
TI  - Proteomics analysis of immunoprecipitated proteins associated with the oncogenic
      kinase cot.
AB  - Cancer Osaka thyroid, also known as Tpl-2 (Cot) is a member of the MAP3K kinase
      family and plays a key role in the regulation of the immune response to pro
      inflammatory stimuli such as lipopolysaccharide (LPS) and tumour necrosis factor
      alpha (TNF-alpha). A series of Cot constructs with an N-terminal 6xHis tag were
      transiently expressed in HEK293 cells: Cot(130-399) (kinase domain), Cot(1-388)
      (N-terminal and kinase domains), Cot(1-413), Cot(1-438) (containing a putative
      PEST sequence), Cot(1-457) (containing both PEST and degron sequences) and Cot(1
      467) (full-length protein). These Cot proteins were pulled down using an anti
      6xHis antibody and separated by 2D electrophoresis. The gels were silver-stained
      and 21 proteins were detected that did not appear, or had substantially reduced
      intensity, in the control sample. Three of these were identified by MS and MS/MS
      analysis as Hsp90, Hsp70 and Grp78. Hsp90 appeared to bind to the kinase domain
      of Cot and this interaction was further investigated using co-immuno
      precipitation with both overexpressed Cot in HEK293 cells and endogenous Cot in
      Hela cells.

PMID- 18319613
TI  - Human vesicular glutamate transporters functionally complement EAT-4 in C.
      elegans.
AB  - The vesicular glutamate transporter (VGLUT) transports glutamate into pre
      synaptic vesicles. Three isoforms of VGLUT have been identified in humans, but
      their functional differences remain largely unknown. EAT-4 is the only homologue
      of human VGLUT in C. elegans. Here we report that mutants of eat-4 exhibit
      hyperforaging behavior and that each of the isoforms of human VGLUT functionally
      rescues the defects in eat-4 worms.

PMID- 18319614
TI  - Transduction of familial amyotrophic lateral sclerosis-related mutant PEP-1-SOD
      proteins into neuronal cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder
      characterized by the selective death of motor neurons. Mutations in the SOD1 gene
      are responsible for a familial form of ALS (FALS). Although many studies suggest
      that mutant SOD1 proteins are cytotoxic, the mechanism is not fully understood.
      To investigate the role of mutant SOD1 in FALS, human SOD1 genes were fused with
      a PEP-1 peptide in a bacterial expression vector to produce in-frame PEP-1-SOD
      fusion proteins (wild type and mutants). The expressed and purified PEP-1-SOD
      fusion proteins were efficiently transduced into neuronal cells. Neurones
      harboring the A4V, G93A, G85R, and D90A mutants of PEP-1-SOD were more vulnerable
      to oxidative stress induced by paraquat than those harboring wild-type proteins.
      Moreover, neurones harboring the mutant SOD proteins had lower heat shock protein
      (Hsp) expression levels than those harboring wild-type SOD. The effects of the
      transduced SOD1 fusion proteins may provide an explanation for the association of
      SOD1 with FALS, and Hsps could be candidate agents for the treatment of ALS.

PMID- 18319615
TI  - CD4+CD25+ regulatory T cells selectively diminish systemic autoreactivity in
      arthritic K/BxN mice.
AB  - Although the arthritis symptoms observed in the K/BxN model have been shown to be
      dependent on the functions of T and B cells specific to the self antigen glucose
      6-phosphate isomerase, less is known about the in vivo roles of CD4(+)CD25(+)
      regulatory T (T(reg)) cells in the pathology of K/BxN mice. We determined the
      quantitative and functional characteristics of the T(reg) cells in K/BxN mice.
      These mice contained a higher percentage of Foxp3(+) T(reg) cells among the
      CD4(+) T cells than their BxN littermates. These T(reg) cells were anergic and
      efficiently suppressed the proliferation of naive CD4(+) T cells and cytokine
      production by effector CD4(+) T cells in vitro. Antibody-mediated depletion of
      CD25(+) cells caused K/BxN mice to develop multi-organ inflammation and
      autoantibody production, while the symptoms of arthritis were not affected. These
      results demonstrate that despite the inability of the T(reg) cells to suppress
      arthritis development, they play a critical role protecting the arthritic mice
      from systemic expansion of autoimmunity.

PMID- 18319616
TI  - Proteomic identification of differentially expressed proteins in Arabidopsis
      mutant ntm1-D with disturbed cell division.
AB  - Proteome analysis was performed to identify proteins differentially expressed in
      an Arabidopsis mutant, ntm1-D. In this mutant the NAC transcription factor NTM1
      is constitutively expressed and the resultant phenotypic changes include
      dwarfism, serrated leaves, and altered floral structures, probably due to reduced
      cell division. Marked elevation of proteins mediating environmental stress
      responses, including annexin, vegetative storage proteins, beta-glucosidase
      homolog 1, and glutathione transferases was observed. Overexpression of annexin
      was confirmed by RT-PCR and Western blotting. These observations suggest that the
      reduced growth observed in the ntm1-D mutant is caused by enhancement of its
      stress responses, possibly resulting in a cost in fitness.

PMID- 18319617
TI  - The fast skeletal muscle myosin light chain is differentially expressed in smooth
      muscle cells of OVA-challenged mouse trachea.
AB  - In a search for new molecular pathways associated with asthma, we performed an
      mRNA differential display analysis using total RNA extracted from the tracheal
      tissues of ovalbumin (OVA)-challenged mice and sham controls. cDNAs corresponding
      to mRNAs for which expression levels were altered by OVA-challenge were isolate
      and sequenced. Twenty-eight genes differentially expressed in sham and OVA
      challenged mice were identified. A GenBank BLAST homology search revealed that
      they were related to cytoskeleton remodeling, transcription, protein synthesis
      and modification, energy production, and cell growth and differentiation. Two
      were selected for further characterization. Up-regulation of both the perinatal
      skeletal myosin heavy chain (skMHC) and fast skeletal muscle myosin light chain
      (skMLC) genes was confirmed by RT-PCR of trachea tissue from OVA challenged mice.
      Overexpression of skMLC protein was observed in the smooth muscle layers of OVA
      challenged mice by immunohistochemistry, and the surface areas stained with skMLC
      antibody increased in the OVA-challenged mice. The overexpression of skMLC in
      murine asthma may be associated with the changes of bronchial smooth muscle.

PMID- 18319618
TI  - HS 1-associated protein X-1 is cleaved by caspase-3 during apoptosis.
AB  - Caspase-3 (CASP3) plays a key role in apoptosis. In this study, HAX-1 was
      identified as a new substrate of CASP3 during apoptosis. HAX-1 was cleaved by
      CASP3 during etoposide-(ETO) induced apoptosis, and this event was inhibited by a
      CASP3-specific inhibitor. The cleavage site of HAX-1, at Asp(127), was located
      using N-terminal amino acid sequencing of in vitro cleavage products of
      recombinant HAX-1. Overexpression of HAX-1 inhibited ETO-induced apoptotic cell
      death. It also inhibited CASP3 activity. Together, these results suggest that HAX
      1, a substrate of CASP3, inhibits the apoptotic process by inhibiting CASP3
      activity.

PMID- 18319619
TI  - Involvement of amino acids flanking Glu7.32 of the gonadotropin-releasing hormone
      receptor in the selectivity of antagonists.
AB  - The Glu/Asp(7.32) residue in extracellular loop 3 of the mammalian type-I
      gonadotropin-releasing hormone receptor (GnRHR) interacts with Arg(8) of GnRH-I,
      conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously,
      we demonstrated that the residues (Ser and Pro) flanking Glu/Asp(7.32) also play
      a role in the differential agonist selectivity of mammalian and non-mammalian
      GnRHRs. In this study, we examined the differential antagonist selectivity of
      wild type and mutant GnRHRs in which the Ser and Pro residues were changed.
      Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist,
      exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs,
      respectively. The inhibitory activities of the antagonists were dependent on
      agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif
      was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity
      to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1
      with the SEP motif had the reverse antagonist selectivity, with reduced
      sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These
      findings indicate that the residues flanking Glu(7.32) are important for
      antagonist as well as agonist selectivity.

PMID- 18319620
TI  - Contribution of TLR2 to the initiation of ganglioside-triggered inflammatory
      signaling.
AB  - Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many
      neuronal diseases, but the precise molecular mechanisms underlying their
      pathological activities are poorly understood. Here we report that TLR2
      participates in the initiation of ganglioside-triggered inflammatory signaling
      responses. Using FACS analysis and immunofluorescence microscopy, we found that
      gangliosides rapidly enhanced the cell surface expression of TLR2 in microglia,
      while reducing that of TLR4. The ganglioside-dependent increase of TLR2
      expression was also observed at the messenger and protein levels. We also showed
      that gangliosides stimulate the interaction of TLR2 with Myd88, an adaptor for
      TLRs, and obtained evidence that lipid raft formation is closely associated with
      the ganglioside-induced activation of TLR2 and subsequent inflammatory signaling.
      These results collectively suggest that TLR2 contributes to the ability of
      gangliosides to cause inflammatory conditions in the brain.

PMID- 18319621
TI  - Gamma-irradiation enhances RECK protein levels in Panc-1 pancreatic cancer cells.
AB  - Radiotherapy is an important treatment for many malignant tumors, but there are
      recent reports that radiation may increase the malignancy of cancer cells by
      stimulating expression of type IV collagenases. In this study, we examined
      changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue
      inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to
      irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein
      levels but not mRNA levels, whereas no significant changes were found in TIMP-1
      and TIMP-2. The enhanced RECK protein levels were associated with an increase in
      MMP inhibitory activity. However, irradiation slightly but reproducibly increased
      the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells
      with transforming growth factor (TGF)-Beta1 led to a 2-fold increase in RECK
      protein levels. Transient transfection with Smad3 also increased RECK protein
      levels, but transfection with Smad7 markedly reduced them. Stable expression of
      Smad7 and treatment with SB431542, an inhibitor of TGF-Beta receptor I kinase,
      abolished TGF-Beta1- and radiation-mediated effects on RECK. Furthermore,
      irradiation increased levels of phosphorylated Smad3. We conclude that radiation
      post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in
      part, via TGF-Beta signaling, and that irradiation increases Panc-1 invasiveness
      via a mechanism that may not be linked to MMP-2 activity.

PMID- 18319622
TI  - Molecular cloning and expression of a laccase from Ganoderma lucidum, and its
      antioxidative properties.
AB  - Laccases are multicopper-containing oxidases that catalyze the oxidation of many
      aromatic compounds with concomitant reduction of oxygen to water. Interest in
      this enzyme has arisen in many fields of industry, including detoxification, wine
      stabilization, paper processing, and enzymatic conversion of chemical
      intermediates. In this study, we cloned a laccase gene (GLlac1) from the white
      rot fungus Ganoderma lucidum. The cloned gene consists of 4,357 bp, with its
      coding region interrupted by nine introns, and the upstream region has putative
      CAAT and TATA boxes as well as several metal responsive elements (MREs). We also
      cloned a full-length cDNA of GLlac1, which contains an uninterrupted open reading
      frame (ORF) of 1,560 bp coding for 520 amino acids with a putative 21-residue
      signal sequence. The DNA and deduced amino acid sequences of GLlac1 were similar
      but not identical to those of other fungal laccases. GLlac1 was released from the
      cells when expressed in P. pastoris, and had high laccase activity. In addition,
      GLlac1 conferred antioxidative protection from protein degradation, and thus may
      be useful in bio-medical applications.

PMID- 18319623
TI  - A forward genetic approach for analyzing the mechanism of resistance to the anti
      cancer drug, 5-fluorouracil, using Caenorhabditis elegans.
AB  - Pyrimidine antagonists including 5-Fluorouracil (5-FU) have been used in
      chemotherapy for cancer patients for over 40 years. 5-FU, especially, is a
      mainstay treatment for colorectal cancer. It is a pro-drug that is converted to
      the active drug via the nucleic acid biosynthetic pathway. The metabolites of 5
      FU inhibit normal RNA and DNA function, and induce apoptosis of cancer cells. One
      of the major obstacles to successful chemotherapy is the resistance of cancer
      cells to anti-cancer drugs. Therefore, it is important to elucidate resistance
      mechanisms to improve the efficacy of chemotherapy. We have used C. elegans as a
      model system to investigate the mechanism of resistance to 5-FU, which induces
      germ cell death and inhibits larval development in C. elegans. We screened 5-FU
      resistant mutants no longer arrested as larvae by 5-FU. We obtained 18 mutants
      out of 72,000 F1 individuals screened, and mapped them into three complementation
      groups. We propose that C. elegans could be a useful model system for studying
      mechanisms of resistance to anti-cancer drugs.

PMID- 18319624
TI  - Expression of Kir2.1 channels in astrocytes under pathophysiological conditions.
AB  - Astrocyte ion channels participate in ionic homeostasis in the brain. Inward
      rectifying potassium channels (Kir channels) in astrocytes have been particularly
      implicated in K(+) homeostasis because of their high open probability at resting
      potential and their increased conductance at high concentrations of extracellular
      K(+). We examined the expression of the Kir2.1 subunit, one of the Kir channel
      subunits, in the mouse brain by immunohistochemistry. Kir2.1 channels were widely
      distributed throughout the brain, with high expression in the olfactory bulb and
      the cerebellum. Interestingly, they were abundantly expressed in astrocytes of
      the olfactory bulb, while astrocytes in other brain regions including the
      hippocampus did not show any detectable expression. However, Kir2.1 channel
      expressing cells were dramatically increased in the hippocampus by kainic acid
      induced seizure and the cells were glial fibrillary acidic protein (GFAP)
      positive, which confirms that astrocytes in the hippocampus express Kir2.1
      channels under pathological conditions. Our results imply that Kir2.1 channels in
      astrocyte may be involved in buffering K(+) against accumulated extracellular
      K(+) caused by neuronal hyperexcitability under phathophysiological conditions.

PMID- 18319625
TI  - v-Crk induces Rac-dependent membrane ruffling and cell migration in CAS-deficient
      embryonic fibroblasts.
AB  - Crk-associated substrate (CAS) is a focal adhesion protein that is involved in
      integrin signaling and cell migration. CAS deficiency reduces the migration and
      spreading of cells, both of which are processes mediated by Rac activation. We
      examined the functions of v-Crk, the oncogene product of the CT10 virus p47gag
      crk, which affects cell migration and spreading, membrane ruffling, and Rac
      activation in CAS-deficient mouse embryonic fibroblasts (CAS-/- MEFs). CAS-/-
      MEFs showed less spreading than did CAS+/+ MEFs, but spreading was recovered in
      mutant cells that expressed v-Crk (CAS-/-v-Crk MEF). We observed that the
      reduction in spreading was linked to the formation of membrane ruffles, which
      were accompanied by Rac activation. In CAS-/- MEFs, Rac activity was
      significantly reduced, and Rac was not localized to the membrane. In contrast,
      Rac was active and localized to the membrane in CAS-/-v-Crk MEFs. Lamellipodia
      protrusion and ruffle retraction velocities were both reduced in CAS-/- MEFs, but
      not in CAS-/-v-Crk MEFs. We also found that microinjection of anti-gag antibodies
      inhibited the migration of CAS-/-v-Crk MEFs. These findings indicate that v-Crk
      controls cell migration and membrane dynamics by activating Rac in CAS-deficient
      MEFs.

PMID- 18319626
TI  - Backbone 1H, 15N, and 13C resonance assignments and secondary-structure of the
      conserved hypothetical protein HP0892 of Helicobacter pylori.
AB  - HP0892 (SwissProt/TrEMBL ID O25552) is a 90-residue conserved hypothetical
      protein from Helicobacter pylori strain 26695, with a calculated pI of 9.38 and a
      molecular mass of 10.41 kDa. It belongs to the Plasmid stabilization system
      protein family (PF05016) in the Pfam database. Proteins with sequence similarity
      to HP0892 exist in Vibrio choierae, Enterococcus faecalis, Campylobacter jejuni,
      Streptococcus pneumoniae, Haemophilus influenzae, Escherichia coli O157. Here we
      report the sequence-specific backbone resonance assignments of HP0892 using
      multidimentional heteronuclear NMR spectroscopy. About 97.0% (422/ 435) of the
      HN, N, CO, C Alpha , C Beta resonances of 90 residues of HP0892 were assigned. On
      the basis of the resonance assignments, three helical regions and four strand
      regions were identified using the CSI program. This study is a prerequisite for
      calculating the solution structure of HP0892, and will be useful for studying its
      interaction with other molecules.

PMID- 18319627
TI  - Characterization of the bovine endogenous retrovirus beta3 genome.
AB  - We recently used degenerate PCR and locus-specific PCR methods to identify the
      endogenous retroviruses (ERV) in the bovine genome. Using the ovine ERV
      classification system, the bovine ERVs (BERVs) could be classified into four
      families. Here, we searched the most recently released bovine genome database
      with the partial nucleotide sequence of the pro/pol region of the BERV beta3
      family. This allowed us to obtain and analyze the complete genome of BERV beta3.
      The BERV beta3 genome is 7666 nucleotides long and has the typical retroviral
      organization, namely, 5'-long terminal repeat (LTR)-gag-pro-pol-env-LTR-3'. The
      deduced open reading frames for gag, pro, pol and env of BERV Beta en- code 507,
      271, 879 and 603 amino acids, respectively. BERV beta3 showed little amino acid
      similarity to other betaretroviruses. Phylogenetic analysis showed that it
      clusters with HERV-K. This is the first report describing the genetic structure
      and sequence of an entire BERV.

PMID- 18319628
TI  - Severe hypoglycemia in a patient with anorexia nervosa.
AB  - OBJECTIVE: Severe hypoglycemia is an important but uncommon complication of
      anorexia nervosa. A 35-year-old woman showed severe hypoglycemia after a recovery
      from severe liver dysfunction due to malnutrition. METHODS: To reveal the cause
      of severe hypoglycemia, we measured plasma hormones and performed a 75g oral
      glucose loading test. RESULTS: Fasting serum adrenocorticotropic hormone,
      cortisol, growth hormone, somatostatin, and active ghrelin were elevated. Serum
      free triiodothyronine, leptin, and adiponectin were reduced. Plasma glucose
      fluctuated from 67 to 76 mg/dl after a 75g glucose ingestion, without
      hyperinsulinemia. Serum growth hormone, somatostatin, and active ghrelin levels
      were decreased after glucose ingestion. Plasma glucagon levels were increased and
      remained at high levels at 120 min, and glucose-dependent insulinotropic
      polypeptide (GIP) levels were continuously and remarkably increased after glucose
      ingestion. CONCLUSION: We observed a strongly reduced sensitivity in glucagon
      induced hepatic glycogenolysis, and significantly elevated fasting and
      postprandial GIP levels, and a defective GIP-mediated glucagon secretion, in an
      anorectic patient with severe hypoglycemia.

PMID- 18319629
TI  - Validity of some prediction equations to assess resting energy expenditure (REE)
      in 29 elderly obese subjects (>60 years).
AB  - BACKGROUND AND AIMS: Recent estimates in US have shown that more than a third of
      65 years old subjects are obese. The objective of this study was to test the
      accuracy of six prediction equations to estimate resting energy expenditure (REE)
      in elderly obese subjects (age >60 years). METHODS: Twenty-nine obese Caucasian
      male (n=8) and female (n=21) subjects (age range: 60-77 years) attended the
      Outpatient Clinic of the Neuroscience Department of Naples "Federico II"
      University Medical School (Italy), Section of Aging and Nutrition from January
      2005 to January 2006. Weight, height, BMI and body composition (bioimpedance)
      were measured. REE was measured using a ventilated-hood indirect calorimetry and
      compared to six prediction equations (Harris-Benedict, Fredrix, Mifflin, Owen,
      WHO, Livingston). RESULTS: Mean age and body mass index (BMI) were 65.9+/-4.8
      years and 36.8+/-5.3 kg/m2, respectively. The measured REE was 1658+/-289
      kcal/day. The Harris-Benedict', Owen' and Livingston's equations performed less
      well than the other equations and they showed a tendency towards underestimation.
      The equation with the best REE prediction was the Fredrix's one (DeltaREE=
      19.4kcal/day) with 66% of REE predictions lying within 10% of measured REE.
      CONCLUSIONS: These data support the utilization of the Fredrix's equation to
      calculate REE in obese elderly subjects.

PMID- 18319630
TI  - The association between high parity and obesity in women living in South-eastern
      Turkey.
AB  - BACKGROUND AND AIM: One of the major public health problems in Turkey is the high
      prevalence of obesity, which is particularly frequent among women. As it has been
      reported that parity affects body fat and BMI, the aim of this study was to
      evaluate the association between parity number, socioeconomic status and obesity.
      SUBJECTS AND METHODS: The study involved 286 married or divorced women aged 28-
      80 years (mean age: 46.7+/-9.7), who were divided into two groups depending on
      whether they had experienced three or fewer pregnancies (group 1) or four or more
      pregnancies (group 2). We measured their body weight and height, and waist and
      hip circumferences, calculated their BMI, and determined their body fat
      percentage and fat mass by means of bioelectric impedance. RESULTS: The women in
      group 2 had a higher BMI, a greater fat percentage and fat mass, a larger waist
      circumference and higher waist/hip ratio values than those in group 1, and their
      mean age and illiteracy ratio were also higher. There was a significant
      correlation between parity number and body weight, BMI and hip circumference.
      CONCLUSIONS: Among other risk factors, a high parity number and socioeconomic
      indices may be associated with obesity in women.

PMID- 18319631
TI  - Quality of life (QoL) and motivation for treatment: a female issue?
AB  - OBJECTIVE: The Quality of Life (QoL) of overweight and obese subjects is a widely
      discussed topic. From numerous studies, it emerges that obese persons suffer
      significant damage as result of their overweight in terms of QoL with regard to
      their physical and psychosocial well-being, with greater incidence associated
      with the degree of obesity. Our study aims at evaluating the usefulness of
      specific psychometric tests on the "obese population" that may be effective for
      the overall evaluation of the patient and in identifying specific subgroups on
      the basis of psychometric characteristics relating to QoL and of motivation for
      treatment. METHODS: The study was carried out on a sample of 150 obese subjects
      who approached the Section of Human Nutrition of the University of Pavia
      requesting treatment for weight loss. The persons in the selected sample were
      subjected to a specialized examination during which, as well as collecting all
      the anamnestic information on each individual patient, they were also asked to
      fill out the obesity-specific ORWELL 97 (Obesity Related Well- Being)
      questionnaire and the DBI (Decisional Balance Inventory) questionnaire. RESULTS:
      An analysis of the results indicates that the female group is strongly
      characterized by a lower QoL, as well as by a clearly larger number of failed
      dieting attempts and by a strong motivation to undergo treatment. CONCLUSIONS:
      The evaluation of QoL and motivation for treatment in overweight and obese
      individuals appears to be an effective tool for better identification of the
      subjects and for planning the most appropriate diagnostic approach.

PMID- 18319632
TI  - Family history of anxiety and mood disorders in anorexia nervosa: review of the
      literature.
AB  - OBJECTIVE: To provide a critical review of the research on mood and anxiety
      disorders in relatives of individuals with anorexia nervosa (AN). In the first
      section, we explore methodological issues with these studies. In the second
      section, we present results. METHOD: A Medline search identified studies
      published on family history of mood and anxiety disorders in AN, and was
      complemented by a manual search. Only studies from 1980 to 2006 using strict
      diagnostic criteria for the disorders were included [Feighner and Halmi criteria
      for AN, Reasearch Diagnostic Criteria (RDC), Diagnostic and Statistical Manual of
      Mental Disorders - Third Edition - Revised (DSM-III-R) or DSM - Fourth Edition
      (DSM-IV) for anorexia and other disorders]. RESULTS: A review of the research
      methods used in the studies revealed a number of methodological problems.
      Therefore, we provide only a description of the prevalence of mood and anxiety
      disorders in relatives of individuals with AN. CONCLUSIONS: In the light of the
      methodological issues uncovered, the value of the results of these studies and
      their implications for further study are considered.

PMID- 18319633
TI  - Body dissatisfaction and restrained eating in male juvenile and adult athletes.
AB  - Athletes of light-weight sport classes are under a constant strain to control
      eating and body shape, which can make them prone to develop eating disorders. In
      the present study, cognitive control of eating (restrained eating) and body
      dissatisfaction were investigated in male elite athletes of light-weight and
      heavy-weight classes at different ages. Body dissatisfaction was assessed under
      hunger and satiety. Adult light-weight rowers had extremely high scores of
      restrained eating and a more pronounced body dissatisfaction under hunger
      compared to satiety in contrast to heavy-weight rowers. Juvenile light-weight
      rowers had a pronounced cognitive control of eating behavior while body
      dissatisfaction was not affected by weight-class or hunger. The results suggest
      that extensive participation in a light-weight sport increases the cognitive
      control of eating behavior but not the disinhibition of cognitive control of
      eating. High levels of cognitive control of eating in the adult lightweight
      rowers are accompanied with body dissatisfaction under hunger but not under
      satiety.

PMID- 18319634
TI  - Negative mood induction and unbalanced nutrition style as possible triggers of
      binges in binge eating disorder (BED).
AB  - OBJECTIVE: To investigate whether negative mood and unbalanced nutrition style
      (fat rich/carbohydrate low) synergistically trigger binge eating in overweight
      and obese binge eating disorder (BED) patients. METHODS: Subsequently to
      following an unbalanced or a balanced nutrition plan for three days,
      participants' food intake in a taste test was measured. During the taste test,
      participants were either in a negative or a neutral mood that was induced through
      a guided imagery task. PARTICIPANTS: Sixty-nine overweight and obese women with
      BED (mean age: 36.7 years, mean body mass index: 32.8 kg/m2). MEASUREMENTS:
      Eating behavior was assessed by measuring the amount of eaten food during the
      taste test. Visual analog scales were used to assess negative affect, tension,
      urge to eat, and hunger before and after the mood induction and after the taste
      test. RESULTS: Negative mood and unbalanced nutrition had neither a combined
      synergistic effect nor separate additive effects on the amount of food intake.
      Negative affect and tension decreased after the taste test in the negative mood
      group. CONCLUSIONS: Negative mood does not invariably enhance the risk of binge
      eating behavior. Fat-rich, carbohydrate-low nutrition style did not influence
      food intake during a taste test. This finding questions the role of this specific
      nutrition style as a crucial factor in promoting binge eating. If replicated,
      these findings are important, since they could guide development of treatment
      protocols.

PMID- 18319635
TI  - Psychosocial and behavioral pre-treatment predictors of weight loss outcomes.
AB  - OBJECTIVE: This study tested whether baseline behavioral and psychological
      variables predict weight and fat loss among overweight, non-obese individuals
      participating in a six-month calorie restriction trial. Participants (N=48) were
      randomly assigned to four groups, three of which included a calorie restriction
      program and one of which served as a healthy diet weight maintenance control. For
      the purposes of this study, data were analyzed only for participants assigned to
      the three calorie restriction groups (n=36). Ten psychological and behavioral
      measures were investigated through principal components factor analysis to
      examine whether these measures were assessing similar or distinct psychological
      and behavioral constructs. Based on the obtained six-factor solution, one measure
      from each domain was selected for inclusion in hierarchical regression analyses,
      which was used to test the relative importance of psychosocial and behavioral
      variables in predicting percent weight and fat loss over six months. After
      controlling for demographic and treatment variables, the behavioral and
      psychological measures of negative mood states, poor psychosocial functioning,
      and somatic symptoms were associated with less weight loss (R2=0.68, p<0.001) and
      fat loss (R2=0.65, p<0.001) over six months. Among overweight individuals, poor
      psychological adjustment, somatic symptoms, and negative mood states appear to
      form a psychosocial profile that is predictive of less weight and fat loss in
      calorie restriction programs.

PMID- 18319636
TI  - A prospective study of predictors of successful weight maintenance by women
      enrolled in community-based weight-loss programs.
AB  - OBJECTIVE: Research is limited on the psychological predictors of successful long
      term weight maintenance after weight loss. Therefore, the present study examined
      the individual contributions of body image, depression, and self-esteem to
      successful weight maintenance after a significant weight loss. METHOD: Measures
      of depression, self-esteem, and body image were administered at baseline, three-,
      and twelve-months to 73 women enrolled in community- based weight loss programs.
      RESULTS: Significant predictors of weight maintenance included baseline self
      classified weight, early (3 months) weight maintenance, later (12 months) change
      in perceptual body image, and the interaction between early and late change in
      body image avoidance. Classifying oneself as more overweight at baseline
      predicted less weight maintenance, while later discrepancies between current and
      realistic body size were positively associated with weight maintenance. Those who
      showed steady improvements in body image avoidance behavior were more likely to
      maintain weight loss. Baseline BMI, self-esteem, and depression did not predict
      12-month weight maintenance. DISCUSSION: Further understanding how body image and
      related factors contribute to weight maintenance may inform development of more
      effective interventions to promote long-term weight maintenance.

PMID- 18319637
TI  - Oral ingestion of a hydrolyzed gelatin meal in subjects with normal weight and in
      obese patients: Postprandial effect on circulating gut peptides, glucose and
      insulin.
AB  - Gut hormones [ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1)] are
      an important group of hormones that target appetite control. They are released
      from endocrine L cells of the small bowel in proportion to the volume, components
      and calories in a meal. In the current study, 20 g of gelatin (flavored and
      sweetened) were given to obese patients (n=12) and lean subjects (n=10).
      Subsequently, plasma samples were collected at-30- minute intervals up to 180
      minutes and glucose, insulin, PYY, GLP-1 and ghrelin were assayed using specific
      and sensitive immunofluorometric and radioimmunoassays. As expected, obese
      patients had normal serum glucose levels, higher serum insulin, and lower plasma
      concentration of ghrelin at all times compared to lean subjects. GLP-1 plasma
      levels were significantly elevated at 60 minutes, peaking at 120 minutes in obese
      patients and lean subjects. As a consequence, there was a significant rise in
      serum insulin levels with a significantly higher peak level at 60 min (obese) and
      30 min (lean). There were no significant changes in PYY plasma concentrations and
      no correlation was found between body mass index and concentrations of ghrelin,
      PYY and GLP-1 in the group of obese patients. In conclusion, a single gelatin
      meal induces a rise in plasma GLP-1 followed by an increase in serum levels of
      insulin. These findings may be applied to maximize satiety in obese patients as a
      means of improving adherence to calorie-controlled diets as well as provide
      better control of diabetic patients.

PMID- 18319638
TI  - Compensatory mechanisms and the type of injury determine the fate of cells with
      impaired macroautophagy.
AB  - The relationship between the degradative process of autophagy and cellular death
      pathways remains unclear. Macroautophagy may potentially function to prevent or
      promote cell death, and both effects have been reported in studies of cells with
      a block in macroautophagy. To better delineate the function of macroautophagy in
      cell death, we contrasted the responses to death stimuli in wild-type and atg5(-/
      ) murine embryonic fibroblasts. We have reported that a knockout of the critical
      macroautophagy gene ATG5 sensitizes cells to death receptor ligand-induced death
      from Fas and tumor necrosis factor-alpha. Death occurs by caspase-dependent
      apoptosis resulting from activation of the mitochondrial death pathway. In
      contrast, atg5(-/-) cells are more resistant to death induced by oxidative stress
      from menadione or UV light. This resistance was associated with an upregulation
      of chaperone-mediated autophagy. Inhibition of this form of autophagy sensitizes
      cells to death from menadione, suggesting that the compensatory upregulation of
      chaperone-mediated autophagy, and not the loss of macroautophagy, prevents death
      from menadione. These findings demonstrate that the effects of a loss of
      macroautophagy on the cellular death response differ depending on the mechanism
      of cellular injury and the compensatory changes in other forms of autophagy.

PMID- 18319639
TI  - Apoptosis meets autophagy-like cell death in the ischemic penumbra: Two sides of
      the same coin?
AB  - Autophagy is a homeostatic cellular process required for the recycling of
      proteins and damaged organelles, and in most scenarios is believed to promote
      cell survival. However, there is accumulating evidence that under certain
      pathological situations, autophagy can also trigger and mediate programmed cell
      death (type II death). Despite the well-established pathophysiological role of
      apoptosis (type I cell death) in post-ischemic neuron death, there is now
      increasing interest whether alternative types of programmed cell death might be
      involved in regulation of neuronal death after both global and focal cerebral
      ischemia. Initial studies demonstrating the involvement of lysosomal proteases of
      the cathepsin family in neuron death after global ischemia already had suggested
      that this type of cell death may occur in an autophagy-dependent manner. Recently
      it was also shown that focal ischemia is associated with potently enhanced
      expression of the autophagy regulator Beclin 1 and subcellular redistribution of
      the autophagic marker LC3 to vacuolic structures in ischemic neurons. Increasing
      evidence suggests that the effects of autophagy are highly contextual. An
      insufficient autophagic response might render cells more susceptible to stress
      conditions whereas on the other hand prolonged overactivation of autophagy can
      lead to a complete self digestion of the cell. The extent of autophagy may
      represent a master switch between cell survival and cell death, and it will be of
      fundamental importance to dissect whether autophagy is primarily a strategy for
      survival or whether autophagy can also be a part of a cell death program and thus
      contribute to cell death after cerebral ischemia. A profound understanding of the
      biological effects and the mechanisms underlying ischemia-induced autophagy in
      neurons might be helpful in seeking effective new treatments for cerebral
      ischemia.

PMID- 18319640
TI  - Eating on the fly: function and regulation of autophagy during cell growth,
      survival and death in Drosophila.
AB  - Significant progress has been made over recent years in defining the normal
      progression and regulation of autophagy, particularly in cultured mammalian cells
      and yeast model systems. However, apart from a few notable exceptions, our
      understanding of the physiological roles of autophagy has lagged behind these
      advances, and identification of components and features of autophagy unique to
      higher eukaryotes also remains a challenge. In this review we describe recent
      insights into the roles and control mechanisms of autophagy gained from in vivo
      studies in Drosophila. We focus on potential roles of autophagy in controlling
      cell growth and death, and describe how the regulation of autophagy has evolved
      to include metazoan-specific signaling pathways. We discuss genetic screening
      approaches that are being used to identify novel regulators and effectors of
      autophagy, and speculate about areas of research in this system likely to bear
      fruit in future studies.

PMID- 18319641
TI  - Autophagy research on insects.

PMID- 18319675
TI  - Trans fat. Time for an oil change.

PMID- 18319676
TI  - Is HPV testing better than a pap test? Not just yet.

PMID- 18319677
TI  - Hospice. Easing life's final phase.

PMID- 18319678
TI  - Mayo Clinic office visit. Finding reliable health information on the Internet.

PMID- 18319679
TI  - Dealing with risk. Facing the certainty of uncertainty.

PMID- 18319680
TI  - One on one. Should I be concerned about the "cherry spots" on my chest?

PMID- 18319681
TI  - One on one. Is it dangerous to sit in one position for too long, such as for a
      long flight?

PMID- 18319682
TI  - Endoscopic transpapillary gallbladder drainage: 10-year single center experience.
AB  - AIM: A subset of patients with acute cholecystitis is severely ill and extremely
      high-risk to undergo cholecystectomy. Data on the use of endoscopic
      transpapillary gallbladder drainage (ETGBD) in the treatment of acute
      cholecystitis are limited. This article reviews the 10-year experience of ETGBD
      at Mayo Clinic and evaluated patient and procedure characteristics. METHODS: A
      retrospective review of the endoscopy database from 1998-2007 was performed to
      identify patients who had undergone ETGBD. Clinical information and procedure
      details were abstracted from the electronic medical record. RESULTS: Fifty one
      patients underwent ETGBD for acute cholecystitis between 1998 to July 2007. The
      mean age was 62+/-19 years and 67% of patients were males. The median number of
      comorbid medical conditions was two (range 0-5) and 27% had underlying diabetes
      mellitus. Acute calculous cholecystitis was the predominant indication for ETGBD
      (78%). A gallbladder stent was used in 33 (65%) patients, nasocholecystic drain
      in 14 (27%) patients, and both in four patients (8%). Bleeding (4%) and sedation
      related complications (4%) were the most common complications noted. Among
      patients who underwent cholecystectomy, the majority (76%) needed an open
      procedure. The median time to cholecystectomy was 15 days (range 1-352 days).
      Four patients (8%) succumbed to septic shock during their hospitalization.
      CONCLUSIONS: ETGBD is a valuable alternative therapeutic modality for the
      treatment of patients with acute cholecystitis who are at high-risk for early
      cholecystectomy, and/or those who have contraindications to percutaneous
      gallbladder drainage.

PMID- 18319683
TI  - Gastroenterology in Italian clinical practice. The RING Study: six years' data
      from gastroenterology departments.
AB  - AIM: Computer systems in hospitals provide information on the work of each single
      operative unit and the complexity of its caselist. However, in Italy, there is no
      official data-base for Gastroenterology Departments, to summarize their work.
      METHODS: The RING (Ricerca-INformatizzata-in-Gastroenterologia) study has
      collected, through a software made on purpose, 113 237 hospital discharge files
      (HDF) from 55 Italian hospital Gastroenterology Units, since 2001. This caselist
      provides a picture of the patients and is useful for clinical/management
      evaluation. RESULTS: Between January 2001 and December 2006, 55 Gastroenterology
      Units gathered 88240 HDF referring to ''ordinary admissions''. The male:female
      rate was 1:1, mean age was 61.3+/-18.5 years. Mean hospital stay was around eight
      days. Over the years there was a significant drop in DRG183 (miscellaneous
      digestive disorders-without complications) from 11.5% to 7.4% (P<0.0001), with no
      similar increase in DRG182 (with complications) which rose from 3.1% to 4.0%.
      Principal discharge diagnoses are post-hepatic and alcohol-related cirrhosis,
      hepatocarcinoma, acute pancreatitis, duodenal/gastric ulcer. CONCLUSIONS: The
      RING data show that the gastroenterologist has been working increasingly with
      patients whose pathologies would have been ''inappropriately'' treated surgically
      (DRGs 204 and 174). Inappropriate gastroenterological treatment seems to have
      decreased as well as the DRG183 with no apparent ''opportunistic'' compensatory
      increase in DRGs with complications, such as 182.

PMID- 18319684
TI  - EUS in gastroenterology. New challenges after Turin 2007.

PMID- 18319685
TI  - Endoscopic ultrasound and fine needle aspiration for the diagnosis of
      hepatocellular carcinoma.
AB  - Liver cancer is one of the most frequent solid cancers. The major risk factor
      associated with the development of hepatocellular carcinoma (HCC) is cirrhosis
      caused by hepatitis B, hepatitis C virus or chronic alcohol consumption. The
      overall prognosis of patients with HCC is very poor and this is mainly due to the
      advanced stages of cancer at presentation and also because of underlying
      cirrhosis. When HCC is diagnosed at early stages, prognosis is better with five
      year disease free survival of around 50% with resection, or local ablative
      treatments such as radio-frequency ablation or percutaneous ethanol injection,
      and 70-80% with liver transplantation. Therefore, systematic screening of all the
      high-risk patients is the key to an early diagnosis of small HCC and the use of
      an appropriate treatment modality. The currently available tools for the
      screening, surveillance and diagnosis of HCC in the presence of cirrhosis remain
      sub-optimal. The advancements made in the past 10 years, however, have made HCC a
      potentially curable disease in a highly selected group of patients. This review
      will briefly discuss the current guidelines for surveillance and diagnosis of HCC
      in high-risk subjects and then review the potential role of endoscopic ultrasound
      and fine needle aspiration for the diagnosis of small HCC.

PMID- 18319686
TI  - Endoscopic ultrasonography in hepatology: focus on portal hypertension.
AB  - Portal hypertension (PHT) is more frequently caused by cirrhosis. Increase in
      portal pressure induces development of collateral circulation with shunting
      resulting in disturbances such as gastroesophageal varices (GEV). Prevention and
      therapy of bleeding from GEV are mandatory. Therefore, the diagnosis of PHT
      represents a crucial step. Endoscopic ultrasound (EUS), with its combination of
      endoscopic imaging and ultrasonic capabilities, can offer an almost comprehensive
      evaluation of portal venous system and porto-systemic collateral circulation. The
      improved endoscopic view of several video-echoendoscopes has filled the gap
      between EUS and standard video-endoscopy in diagnosing GEV and in assessing
      endoscopic criteria of bleeding risk. EUS combined with Color-Doppler
      capabilities are able to provide hemodynamic information. Furthermore, EUS data
      allow to stratify patients on the basis of PHT severity and first bleeding risk,
      monitor the results of pharmacologic and/or endoscopic therapy, predict the
      response to treatment, quantify the risk of variceal recurrence and recurrent
      bleeding after GEV obliteration and guide or assist EGD therapy. Despite having
      this amount of information, there is lack of scientific evidence that EUS imaging
      and EUS-assisted therapy can have a clear-cut clinical impact and affect patients
      outcome.

PMID- 18319687
TI  - Endoscopic management of biliary leaks. The answer for the future.
AB  - Bile duct diseases and biliary leaks are not uncommon complications and their
      management is challenging. Majority of bile leaks occur secondary to trauma,
      major liver, gallbladder and biliary tract surgeries. Early recognition of bile
      leaks by imaging combined with a high clinical suspicion is required. Bile leaks
      can be managed either conservatively, or through percutaneous drainage, or
      endoscopically or by surgical intervention. The innovations in endoscopic
      techniques have expanded the horizons for managing patients with bile leaks
      irrespective of their etiology. Endoscopic interventions through biliary
      sphincterotomy alone, biliary stenting with or without sphincterotomy, and
      nasobiliary drainage with or without sphincterotomy, use of self expanding
      covered metal stents and the recent use of biodegradable stents have been very
      effective in the management of all kinds of biliary leaks. All endoscopic
      techniques are based on the principle that eliminating the rise in pressure
      inside the bile duct by promoting decompression in the form of stent
      placement/sphincterotomy promotes healing of bile leaks. Further future
      developments in endoscopic techniques are expected to improve their effectiveness
      in managing patients with bile leaks.

PMID- 18319688
TI  - Endoscopic ultrasound (EUS) guided access and therapy of pancreatico-biliary
      disorders.
AB  - Endoscopic ultrasound (EUS) has evolved from a purely diagnostic imaging modality
      to one that allows therapeutic intervention. It now serves as a viable
      alternative, and at times is preferred, to percutaneous and surgical techniques
      for obtaining biliary and pancreatic duct access and for providing drainage. EUS
      guided intervention is usually performed following failed endoscopic retrograde
      cholangiopancreatography (ERCP) or as an option for patients who decline surgical
      intervention or in poor operative candidates. Published data demonstrate overall
      technical success in 83% of patients with 12% experiencing a procedure related
      complication. New techniques and equipment must be developed to simplify and
      abbreviate the procedures, to limit complications, and improve outcomes. In
      addition, longitudinal data are needed to determine the long-term outcomes and
      role of EUS guided pancreaticobiliary intervention.

PMID- 18319689
TI  - Endoscopic ultrasonography and pancreatic cancer.
AB  - Despite extensive multidisciplinary efforts, the five-year survival rate for all
      patients with pancreatic adenocarcinoma remains less than 3%. In the last twenty
      years, endoscopic ultrasound (EUS) has developed into an indispensable tool for
      the diagnosis and staging of malignant pancreatic lesions. EUS, in combination
      with helical and multidetector computed tomography scans, is currently 80-90%
      accurate in determining the tumor TNM stage. EUS fine-needle aspiration obtains
      diagnostic pathologic samples in approximately 80% of cases, and intraductal
      ultrasound has augmented the ability to determine the malignant potential of
      pancreatic strictures. In patients at high-risk for pancreatic malignancy, EUS
      has been advocated as a screening tool for malignancy. Finally, exciting new
      developments suggest the potential of EUS as a therapeutic tool, both for the
      management of pain from pancreatic cancer and as a novel therapeutic-delivery
      device.

PMID- 18319690
TI  - An overview of endoscopic ultrasound equipment.
AB  - Endoscopic ultrasound imaging technology has significantly improved over the last
      decade. Innovative design of equipment and devices has broadened the utility of
      EUS as diagnostic and therapeutic tools. Lesions as small as 3 mm can be imaged
      and targeted for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA).
      EUS imaging with the latest generation electronic radial and linear scopes is
      excellent and does not vary significantly between models. Miniprobes should not
      be used in place of routine EUS echoendoscopes when available and technically
      feasible. The drawbacks of ultrasound miniprobes are the inability to perform
      fine needle aspiration and the limited depth of imaging. Transpapillary
      intraductal ultrasound (IDUS) improves staging of biliary tumors and improves
      imaging of biliary and pancreatic duct strictures. Endoscopic ultrasound-guided
      celiac plexus neurolysis or block (EUS-CPN/CPB) can be performed with the EUS-FNA
      needle or a specially designed celiac plexus block needle which distributes the
      neurolytic agent into the celiac plexus in a radial fashion. Use of the core
      biopsy needle is safe and should be used with a therapeutic linear scope through
      the gastric wall.

PMID- 18319691
TI  - Capsule endoscopy: a review from the clinician's perspectives.
AB  - The possibility of visualization of the small bowel has dramatically improved
      with the introduction of capsule endoscopy (CE) and it has rapidly become
      standard practice in investigating diseases of the small bowel. Nowadays, there
      are many reasons to perform CE: most often suspected obscure gastrointestinal
      bleeding, inflammatory bowel disease, celiac disease and small bowel neoplasia.
      CE has higher diagnostic yields than other (more invasive) diagnostic modalities
      for most of these indications. Furthermore, there are virtually no real contra
      indications anymore for the procedure. CE appears also to be safe in selected
      paediatric cases in which it has similar diagnostic yields compared with adults.
      This review is a practical update for the clinician on CE, including the
      complementary role of double balloon enteroscopy and the new developments of
      Pillcam ESO and the Pillcam COLON.

PMID- 18319692
TI  - Treatment regimens for patients with chronic hepatitis C.
AB  - Infection by the hepatitis C virus (HCV) is a major public health problem, with
      more than 170 million people infected throughout the world. The infection
      prevalence, with small regional differences, is estimated in 1-3% of the global
      population. HCV is the most frequent cause of chronic liver disease and 20-30% of
      patients develop cirrhosis with a risk of hepatocellular carcinoma. Nowadays,
      pegylated interferon-a (PEG-IFN) in combination with ribavirin, a nucleoside
      analogue, is the current treatment for chronic hepatitis C (CHC), with less
      adverse effects and better compliance. Dosage and duration depend on some factors
      as weight, genotype, viral load and a rapid virological response presented by the
      patient. One of the most relevant aspects in the treatment of CHC is how to
      manage the group of non-responder or relapser patients to previous treatments. As
      such, a substantial proportion of patients had already been unsuccessfully
      treated with interferon-based therapies and these patients claim for an optimal
      therapeutic option. The future treatment of CHC walk along through the
      association of two or three drugs, including nucleoside/nucleotide analogues,
      higher PEG-IFN initial dosages (induction) or longer treatments duration, or
      combination of helicase and protease inhibitors.

PMID- 18319693
TI  - Hepatitis C virus cirrhosis: prolonged sustained virological response in a
      patient after low-dose antiviral treatment.
AB  - Hepatitis C virus (HCV) infection is the most frequent cause of chronic liver
      disease in the western world. The ''gold standard'' treatment of chronic HCV
      infection currently involves the administration of pegylated interferon alpha
      (PEG-IFN) and ribavirin. The success of this therapy is demonstrated by sustained
      virological responses (SVR). Randomized trials and practice guidelines have
      reported that compensated HCV cirrhosis is an indication for treatment with PEG
      IFN and ribavirin, not only to obtain SVR but also to increase survival and to
      reduce the development of cirrhotic sequelae. In particular, the literature has
      reported that antiviral treatment was associated with histological improvement of
      fibrosis in cirrhotic patients with SVR. Recently, the same authors have
      evaluated the efficacy and safety of different doses of antiviral treatment in
      patients with chronic HCV infection. The use of interferon has been limited due
      to associated side effects, particularly in cirrhotic patients. Consequently,
      therapeutic decisions should be made on an individual basis. The Authors report a
      case of a patient with compensated HCV liver cirrhosis, with associated severe
      thrombocytopenia and oesophageal varices, in which the administration of
      antiviral therapy at a dose lower than the therapeutic ''gold standard'' has
      achieved SVR and consequently improved clinical status.

PMID- 18319694
TI  - Jejunal perforation secondary to metastatic sarcomatoid carcinoma of the lung.
AB  - The Authors present the third case of small-bowel perforation of a metastatic
      sarcomatoid carcinoma of the lung. A 62-year-old man underwent a right upper
      lobectomy because of a lung tumour infiltrating the posterior thoracic wall. The
      histology showed pleomorphic subtype of a sarcomatoid carcinoma (pT3 pN0 cM0).
      The postoperative course was uneventful and thus the patient received 5 000 cGY
      over five weeks. After 5 months the patient was admitted to the Surgical
      Department for acute abdomen. At laparotomy an advanced fibrinous, bile-stained
      peritonitis secondary to a solitary perforation of the jejunum 50 cm distal to
      the Treitz were observed. The microscopical examination showed that the
      perforated mass consisted of infiltration of dischoesive malignant giant cells,
      highly pleomorphic multi and mononucleated. The immunohistochemistry, performed
      with multiple keratin antibodies, revealed epithelial differentiation of
      malignant cells, compatible with a metastatic carcinoma, consistent to the lung
      primary. In conclusion, according with literature, the small-bowel perforation is
      a rare presentation of a metastatic lung carcinoma, and particularly of a
      sarcomatoid carcinoma. It should be considered in differential diagnosis of
      patients with acute abdominal symptoms especially in those with a previous
      treated lung cancer. The surgeons should be aware of the poor outcome of these
      patients and choose a palliative treatment.

PMID- 18319695
TI  - Autoimmune hepatitis in India. Getting to the heart of the matter.

PMID- 18319696
TI  - Evaluation of the left ventricular anatomy in hypertrophic cardiomyopathy:
      comparison between echocardiography and cardiac magnetic resonance imaging.
AB  - AIM: The aim of this study was to assess the relationship between
      echocardiographic indexes of left ventricular (LV) hypertrophy with LV mass (LVM)
      obtained at cardiac magnetic resonance (CMR) in a population of patients with
      hypertrophic cardiomiopathy (HCM). METHODS: Thirty-nine patients with HCM
      underwent echocardiography and CMR. By echocardiography maximal wall thickness
      (MWT), Spirito' and Maron's hypertrophy index and the Wigle's score were
      obtained. Absolute LVM was measured through CMR and indexed to body surface area
      (LVMi). Data were analysed using linear regression analysis. RESULTS: In 31% of
      patients there was an incomplete echocardiographic LV anatomic characterization.
      However, there was a good correlation between MWT measured at echocardiography
      and at CMR (P<0.001; r=0.755). Overall echocardiographic indexes of LV
      hypertrophy correlate with either LVM and LVMi: MWT (P=0.008, r=0.420 and
      P=0.003, r=0.467, respectively); Spirito' and Maron's hypertrophy index (P=0.003,
      r=0.551 and P=0.001, r=0.606, respectively) and Wigle's score (P=0.004, r=0.522
      and P=0.004, r=0.522, respectively). CONCLUSION: In our HCM population, although
      a complete anatomic LV anatomic characterization was not obtained by
      echocardiography in all patients, echocardiographic hypertrophic indexes showed a
      good correlation with LVM obtained by CMR.

PMID- 18319697
TI  - Oxidative stress and inflammation due to peripheral polymorphonuclear leukocytes
      after coronary angiography vs percutaneous coronary intervention.
AB  - AIM: Percutaneous coronary intervention (PCI) as an invasive procedure includes
      inflation of a balloon and/or implantation of an endovascular prosthesis (stent)
      in an atherosclerotic coronary vessel at a level where the plaque narrows its
      cross-sectional area by more than 75%. Various reports have demonstrated that
      balloon inflation or stent implantation trigger inflammation and subsequent
      growth of smooth muscle cells. Both oxidative stress (OS) and inflammation
      parameters worsen, increasing the risk of complications. The polymorphonuclear
      leukocyte (PMNL) is one of the inflammatory cells releasing reactive oxygen
      species contributing to OS, inflammation and endothelial injury. The aim of this
      study was to study the contribution of PMNLs during coronary intervention.
      METHODS: Patients enrolled in this study were randomized into two groups, namely
      nine patients undergoing PCI procedure, compared to 11 undergoing diagnostic
      coronary angiography. PMNLs were separated from patient blood, before and
      following PCI. PMNL priming was measured by rate of superoxide release from PMNLs
      and flow cytometry analysis of CD11b levels. PMNL-related inflammation was
      estimated by white blood cells (WBC) and PMNL count. Systemic inflammation was
      monitored by C-reactive protein (CRP) and fibrinogen. RESULTS: Tested patients
      were divided into patients undergoing PCI procedure, compared to those undergoing
      diagnostic coronary angiography; already at time ''0'', OS and inflammation
      parameters were higher in the PCI group of patients. OS parameters decreased
      significantly following PCI procedure. PCI itself induces increased OS and
      inflammation. Significant positive correlation was found between serum creatine
      phosphokinase and rate of superoxide release from PMNLs, indicating correlation
      between PMNL priming and the severity of cardiac disease. Systemic inflammation
      parameters, such as fibrinogen and CRP, showed significant decrease in the PCI
      group after the procedure, while those related to PMNLs did not. CONCLUSION: PMNL
      contribution to OS and inflammation is lower in patients undergoing diagnostic
      coronary angiography, compared to the PCI group. This research adds new facet to
      evaluation of cardiac patients whether they will undergo PCI procedure or
      diagnostic coronary angiography.

PMID- 18319698
TI  - Reduction incidence of myocardial infarction associated with a national
      legislative ban on smoking.
AB  - AIM: The aim of the present study was to assess change in admissions for acute
      myocardial infarction (AMI) in the period immediately subsequent to the coming
      into force of law no. 3/2003 ''Protection of the health of non-smokers''.
      METHODS: Four Italian regions (Piedmont, Friuli Venezia Giulia, Lazio and
      Campania) took part in the study. Data regarding admissions for AMI were taken
      from the daily discharge papers of patients aged between 40 and 64 (cod. ICD9-CM
      410.), in the period 10 January-10 March 2001-2005. Repeated admissions were
      excluded. Admission rates standardised by age and overall total, and specifically
      by region, age and gender were calculated. The hypothesis of a significant
      reduction between 2005 and 2004 was also checked. RESULTS: The results showed a
      decrease in the number of cases and in the standardised rates between 2004 and
      2005. The number of admissions estimated with a linear regression model for 2005
      was significantly higher than that really observed (+13%). The decrease between
      the 2005 and 2004 rates was noteworthy for all four regions. Analysis by gender
      shows that the effect is observed only in male patients and in the age classes 45
      49 and 50-54. CONCLUSION: This study shows that there has been an appreciable
      reduction in the incidence of heart attacks in the period immediately subsequent
      to the coming into force of the non-smoking Law in the populations surveyed, and
      that this reduction mainly regards men of working age. The reduction reverses a
      trend that has been evident for a number of years, namely that of a decidedly
      upward trend in the number of admissions for AMI.

PMID- 18319699
TI  - Biodegradable stents.
AB  - Bioabsorbable stents must be biocompatible and as well as their degenerated
      products. The challenge is to find material that exhibit minimal recoil and
      remain in situ for several months before complete bio-absorption. There are now
      some worthy polymer based and metallic bioabsorbable stents with encouraging
      preclinical and clinical data. Their behaviour will not only redefine current
      percutaneous coronary intervention but may also have a wider role in the
      cardiovascular system as whole.

PMID- 18319700
TI  - Multi-slice computed tomography coronary angiography: anatomic vs functional
      assessment in clinical practice.
AB  - Non-invasive imaging plays an increasingly important role in the diagnosis and
      risk stratification of coronary artery disease (CAD). Several techniques such as
      stress echocardiography and myocardial perfusion imaging have become available to
      assess cardiac function and myocardial perfusion. With the arrival of multi-slice
      computed tomography coronary angiography (CTA), non-invasive imaging of coronary
      anatomy has also become possible. Studies concerning the diagnostic accuracy have
      demonstrated a good agreement with conventional coronary angiography resulting in
      a sensitivity and specificity of approximately 86% and 96%, respectively. The
      high negative predictive value of 97% renders it particularly useful to rule out
      the presence of CAD in patients with an intermediate pretest likelihood.
      Moreover, comparative studies have demonstrated that anatomic imaging with CTA
      may provide information complementary to the traditionally used techniques for
      functional assessment. From these studies can be derived that only approximately
      50% of significant stenoses on CTA are functionally relevant; a large proportion
      of significant (>50%) lesions on CTA does not result in perfusion abnormalities.
      Alternatively, many patients with a normal perfusion CTA show considerable
      atherosclerosis on CTA. Therefore, the combined use of these techniques may
      enhance the assessment of the presence and extent of CAD. In the future
      diagnostic algorithms, combining non-invasive anatomic and functional imaging
      need to be evaluated in large patient populations to establish their efficacy,
      safety, and cost effectiveness. Importantly, these investigations should result
      in the development of comprehensive guidelines on the use of CTA in clinical
      practice as well.

PMID- 18319701
TI  - Measuring left ventricular mechanical dyssynchrony from ECG-gated SPECT
      myocardial perfusion imaging.
AB  - Cardiac resynchronization therapy (CRT) has shown benefits in patients with
      severe heart failure. The traditional criteria to select patients for CRT (New
      York Heart Association [NYHA] class III or IV, depressed left ventricular [LV]
      ejection fraction, and prolonged QRS duration) result in at least 30% of the
      selected patients with no response to CRT. Recent studies with echocardiography
      have shown that the presence of LV dyssynchrony is an important predictor for
      response to CRT. However, the recent report from the predictors of response to
      cardiac resynchronization therapy (PROSPECT) trial suggested that under ''real
      world'' conditions the current available echocardiographic techniques including
      tissue Doppler imaging (TDI) and myocardial strain-rate imaging are not ready for
      routine clinical practice to assess LV dyssynchrony. Phase analysis is a recently
      developed technique that allows measuring LV dyssynchrony from electrocardiogram
      (ECG)-gated single photon emission computed tomography (GSPECT) myocardial
      perfusion imaging (MPI). This technique uses Fourier harmonic functions to
      approximate regional wall thickening over the cardiac cycle and to calculate
      regional onset of mechanical contraction (OMC) phases. These OMC phases are
      obtained three-dimensionally over the entire left ventricle to quantitatively
      assess the degree of LV dyssynchrony. This technique has been compared to TDI and
      shown promising results in clinical validations. The advantages of this technique
      over echocardiography in measuring LV dyssynchrony are its automation, its high
      repeatability and reproducibility. It can be applied to any conventional GSPECT
      MPI study with no additional procedure. In this review the phase analysis
      methodology is described and its up-to-date clinical validations are summarized.

PMID- 18319702
TI  - Assessment of myocardial viability in ischemic heart disease by cardiac magnetic
      resonance imaging.
AB  - Assessment of myocardial viability aims at differentiating between viable and non
      viable myocardium. The proof of dysfunctional but viable myocardium is crucial to
      predict outcome of revascularization after acute (AMI) and chronic myocardial
      infarction (CMI). Cardiac magnetic resonance imaging (CMRI) offers different
      options to detect viable myocardium: Measurements of end-diastolic wall thickness
      by cine-CMRI can be used to depict chronically scarred myocardium, but fails to
      detect acute myocardial necrosis. Low-dose dobutamine stimulation (LDDS) cine
      CMRI analyses the contractile reserve of dysfunctional but viable myocardium
      under pharmacologic stimulus to identify viable myocardium in AMI and CMI with
      high specificity. Sensitivity of LDDS cine-CMRI is superior to LDDS
      echocardiography but reduced in patients with severely impaired left ventricular
      (LV) function. The delayed-enhancement (DE) technique directly visualises non
      viable myocardium due to an altered contrast-media distribution in necrotic and
      fibrotic tissue. DE-CMRI identifies non-viable myocardium with high spatial
      resolution independently from LV function. The transmural extent of contrast
      enhancement in DE-CMRI is used to predict functional recovery after
      revascularization in AMI and CMI. Furthermore, the amount and pattern of contrast
      enhancement in DE-CMRI provide important prognostic information in both entities.
      Recent studies demonstrated the superiority of DE-CMRI compared to single photon
      emission tomography (SPECT) and positron emission tomography (PET) to assess
      myocardial viability. Therefore, DE-CMRI is currently recognised as the standard
      of reference for assessment of myocardial viability. The technical background,
      clinical application and accuracy of the different CMRI techniques to assess
      myocardial viability in AMI and CMI are discussed in this work.

PMID- 18319703
TI  - Telecardiogram: still of matter in the modern cardiac imaging era?
AB  - The modern cardiovascular imaging era has seen the introduction in clinical
      practice of highly innovative and performing diagnostic features. The negative
      side of this outstanding evolution risks to be an under-assessment of well
      established classical diagnostic techniques. Thereby, to support the actual
      relevance of a properly executed chest X-ray, this article describes two
      paradigmatic cases of exceptional cardiac abnormalities, in which X-rays played a
      key diagnostic role.

PMID- 18319704
TI  - Venture wire control catheter in percutaneous treatment of complex coronary
      bifurcation. A case report.
AB  - We present a case report of a man with atherosclerotic involvement of a left main
      trifurcation treated by the Venture wire control catheter. The patient was
      submitted to primary percutaneous transluminal coronary angioplasty (PTCA) in a
      primary center for acute occlusion of the left anterior descending artery, then
      he was transferred to our tertiary center to perform left main trifurcation
      revascularization that was unsuccessful by traditional approach. In our high
      volume center (operator >600 PTCA/year) as well, the attempts at crossing the
      lesion with a number of different guidewires failed because of the extreme
      angulation of the circumflex artery. At last, a successful attempt was reached
      using the Venture wire control, a low profile catheter with a tip that can be
      deflected up to 90 degrees . Once the lesion was crossed and wiring of other
      branches obtained, crush stenting of the left anterior descending artery and
      intermediate ramus and T-stent of the circumflex artery were performed with an
      optimal angiographic result.

PMID- 18319705
TI  - Multiple cardiac rhabdomyomas at routine fetal ultrasonography.

PMID- 18319706
TI  - Acute chest pain and ST-elevation during patent foramen ovale closure.

PMID- 18319707
TI  - Risk of stent thrombosis after lower-extremity endovascular revascularization:
      which is the optimal antithrombotic therapy and is early strenuous exercise safe?

PMID- 18319708
TI  - Coronary thrombosis in a patient with leukemic thrombocytosis: which was the best
      treatment?

PMID- 18319710
TI  - Mechanisms of disease: autoantigens as clues to the pathogenesis of myositis.
AB  - Autoimmune inflammatory myopathies, referred to as myositis, comprise a
      heterogeneous group of chronic inflammatory muscle diseases that present with
      various clinical phenotypes, histologic changes and autoantibodies, resulting in
      progressive inflammatory muscle damage and weakness. In up to 20% of myositis
      patients, particularly those with dermatomyositis, there is an association with
      cancer that is most frequently diagnosed within 1 year of presentation of
      myositis. Accumulating data show that autoantibodies in myositis target a
      specific group of intracellular molecules that are not muscle-specific in their
      expression. The striking association between autoantibodies recognizing
      ubiquitously expressed molecules and distinct clinical phenotypes suggests that
      the target tissues themselves might regulate and shape the phenotype-specific
      immune response in myositis. Studies indicate that changes in phenotype-specific
      autoantigens, such as altered structure, enhanced expression, and acquisition of
      adjuvant properties during various forms of cellular stress, apoptosis, and
      transformation, might be mechanistically important in this regard. This Review
      discusses these developments and highlights a central role of autoantigens
      themselves as a critical partner in driving autoimmune diseases, and the
      potential for their therapeutic manipulation. In addition, we will highlight
      insights that the cancer-autoimmunity interface in this group of diseases
      provides into the relationship between the anticancer immune response and
      autoimmune diseases.

PMID- 18319711
TI  - Primer: SNP-associated studies and what they can teach us.
AB  - Single-nucleotide polymorphisms (SNPs) are single base-pair alterations in the
      DNA sequence that represent a major source of genetic heterogeneity. Well
      developed and sophisticated technologies exist to measure and analyze the
      presence of SNPs, and SNP genotyping is an important tool with which to
      investigate other genetic variants. SNP-based, large-scale, genome-wide
      association studies are detecting many polymorphisms that can be used to evaluate
      the risk of various common traits, including rheumatic diseases. This increased
      knowledge of genetic risk could potentially be used to refine medical care in
      rheumatology clinics in the near future.

PMID- 18319712
TI  - Global meta-analysis of the C-11377G alteration in the ADIPOQ gene indicates the
      presence of population-specific effects: challenge for global health initiatives.
AB  - Type II diabetes mellitus is currently globally one of the fastest growing non
      communicable diseases, especially in developing countries. This investigation
      reports on a meta-analysis undertaken of the C-11377G locus within the
      adiponectin gene in a black South African, a Cuban Hispanic and a German
      Caucasian cohort. Genotyping was performed via a real-time PCR strategy. Both
      fixed- and random-effects models were tested to describe the diabetes risk at
      both the cohort and population levels. The 2,2 genotype may only be associated
      with increased diabetes risk in the Cuban Hispanic cohort. Population-specific
      effects may have masked these associations upon meta-analytical analysis, as no
      significant odds ratio could be determined. Thus, to examine diabetes risk, a
      more global approach including the design of population-specific experimental
      strategies should be used, which will be crucial in developing health education
      and policies in a global health programme.

PMID- 18319713
TI  - A phase I trial of ispinesib, a kinesin spindle protein inhibitor, with docetaxel
      in patients with advanced solid tumours.
AB  - The aim of this study is to define the maximum tolerated dose (MTD), safety,
      pharmacokinetics (PKs) and efficacy of ispinesib (SB-715992) in combination with
      docetaxel. Patients with advanced solid tumours were treated with ispinesib (6-12
      mg m(-2)) and docetaxel (50-75 mg m(-2)). Docetaxel was administered over 1 h
      followed by a 1-h infusion of ispinesib on day 1 of a 21-day schedule. At least
      three patients were treated at each dose level. Blood samples were collected
      during cycle 1 for PK analysis. Clinical response assessments were performed
      every two cycles using RECIST guidelines. Twenty-four patients were treated at
      four dose levels. Prolonged neutropaenia and febrile neutropaenia were dose
      limiting in six and two patients, respectively. The MTD was ispinesib 10 mg m(-2)
      with docetaxel 60 mg m(-2). Pharmacokinetic assessment demonstrated
      concentrations of ispinesib and docetaxel, consistent with published data from
      single agent studies of the drugs. Seven patients (six hormone refractory
      prostate cancer (HRPC), one renal cancer) had a best response of stable disease
      (>or=18 weeks). One patient with HRPC had a confirmed >50% prostatic-specific
      antigen decrease. The MTD for ispinesib and docetaxel was defined and the
      combination demonstrated an acceptable toxicity profile. Preliminary PK data
      suggest no interaction between ispinesib and docetaxel.

PMID- 18319714
TI  - Population pharmacokinetic data analysis of three phase I studies of matuzumab, a
      humanised anti-EGFR monoclonal antibody in clinical cancer development.
AB  - A population pharmacokinetic model based on data from three phase I studies was
      to be developed including a covariate analysis to describe the concentration-time
      profiles of matuzumab, a novel humanised monoclonal antibody. Matuzumab was
      administered as multiple 1 h i.v. infusions with 11 different dosing regimens
      ranging from 400 to 2000 mg, q1w-q3w. For analysis, 90 patients with 1256 serum
      concentration-time data were simultaneously fitted using the software NONMEM.
      Data were best described using a two-compartment model with the parameters
      central (V1) and peripheral distribution volume (V2), intercompartmental (Q) and
      linear (CLL) clearance and an additional nonlinear elimination pathway (Km,
      Vmax). Structural parameters were in agreement with immunoglobulin
      characteristics. In total, interindividual variability on Vmax, CLL, V1 and V2
      and interoccasion variability on CLL was 22-62% CV. A covariate analysis
      identified weight having an influence on V1 (+0.44% per kg) and CLL (+0.87% per
      kg). All parameters were estimated with good precision (RSE<39%). A robust
      population pharmacokinetic model for matuzumab was developed, including a
      nonlinear pharmacokinetic process. In addition, relevant and plausible covariates
      were identified and incorporated into the model. When correlated to efficacy,
      this model could serve as a tool to guide dose selection for this 'targeted'
      cancer therapy.

PMID- 18319715
TI  - Inhibition of mTOR pathway by everolimus cooperates with EGFR inhibitors in human
      tumours sensitive and resistant to anti-EGFR drugs.
AB  - Inhibition of a single transduction pathway is often inefficient due to
      activation of alternative signalling. The mammalian target of rapamycin (mTOR) is
      a key intracellular kinase integrating proliferation, survival and angiogenic
      pathways and has been implicated in the resistance to EGFR inhibitors. Thus, mTOR
      blockade is pursued to interfere at multiple levels with tumour growth. We used
      everolimus (RAD001) to inhibit mTOR, alone or in combination with anti-EGFR drugs
      gefitinib or cetuximab, on human cancer cell lines sensitive and resistant to
      EGFR inhibitors, both in vitro and in vivo. We demonstrated that everolimus is
      active against EGFR-resistant cancer cell lines and partially restores the
      ability of EGFR inhibitors to inhibit growth and survival. Everolimus reduces the
      expression of EGFR-related signalling effectors and VEGF production, inhibiting
      proliferation and capillary tube formation of endothelial cells, both alone and
      in combination with gefitinib. Finally, combination of everolimus and gefitinib
      inhibits growth of GEO and GEO-GR (gefitinib resistant) colon cancer xenografts,
      activation of signalling proteins and VEGF secretion. Targeting mTOR pathway with
      everolimus overcomes resistance to EGFR inhibitors and produces a cooperative
      effect with EGFR inhibitors, providing a valid therapeutic strategy to be tested
      in a clinical setting.

PMID- 18319717
TI  - The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by
      paclitaxel in ovarian cancers.
AB  - The role of transcriptional factor FOXO1 in the mechanism of drug-resistance in
      ovarian cancer has not been elucidated. In ovarian cancer cell lines, FOXO1
      expression and its correlation with paclitaxel treatment was investigated by
      cytotoxic assay and silencing experiment. Clinical ovarian cancer samples were
      also examined for FOXO1 expression by immunohistochemistry. FOXO1 expression was
      distinctively upregulated in paclitaxel-resistant cell line, and enhanced by
      exposure to paclitaxel. FOXO1 overexpression was frequently observed in tissue
      samples from chemoresistant patients compared to chemosensitive patients. FOXO1
      silencing in paclitaxel-resistant cell line decreased its resistance.
      Modification of oxidative stress by co-treatment with pharmacologic modulators of
      reactive oxygen species attenuated cytotoxicity of paclitaxel. Downstream targets
      of FOXO1 involving oxidative stress were also attenuated in silencing experiment,
      suggesting its involvement in altered sensitivity to paclitaxel. These results
      indicate that FOXO1 links to cytotoxic stress induced by paclitaxel and
      contributes to the drug-resistance in ovarian cancers.

PMID- 18319718
TI  - Tumour-necrosis factor-A polymorphisms and gastric cancer risk: a meta-analysis.
AB  - Inflammation is one of the early phases in the development of gastric cancer.
      Therefore, several studies have examined the association of polymorphisms in
      tumour-necrosis factor-A gene (TNF-A) with gastric cancer risk. This meta
      analysis reviews and summarises published evidence for these associations.
      Searching several databases yielded 24 independent studies that reported on the
      associations between TNF-A polymorphisms and gastric cancer risk. We analysed
      available data for the most commonly investigated polymorphisms: TNF-A -308G>A
      (23 studies), TNF-A -238G>A (9 studies), and TNF-A -857C>T (5 studies). Summary
      odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated in the
      random-effects model using the DerSimonian-Laird method. Q-statistic and I(2)
      statistic were calculated to examine heterogeneity, and funnel plots were plotted
      to examine small study effects. The overall ORs (95% CIs) for AG and AA genotypes
      vs GG genotype for TNF-A -308 were 1.09 (0.94-1.27) and 1.49 (1.11-1.99),
      respectively. For TNF-A -238, the corresponding ORs (95% CIs) were 1.05 (0.84
      1.33) and 1.25 (0.30-5.26), respectively. The overall ORs (95% CIs) for CT and TT
      genotypes (vs CC) for TNF-A -857 were 1.06 (0.89-1.27) and 1.57 (0.91-2.70),
      respectively. The statistically significant association between TNF-A -308GG and
      gastric cancer was limited to western populations. This association showed little
      heterogeneity (I(2)=0) and remained consistently strong when analyses were
      limited to anatomic and histologic subtypes of gastric cancer, or limited to
      studies in which genotype frequencies were in Hardy-Weinberg equilibrium, or
      limited to larger studies. These same subgroup analyses did not change results
      associated with other polymorphisms. In conclusion, TNF-A -308AA genotype was
      associated with a statistically significant increased risk of gastric cancer,
      whereas other studied polymorphisms were not. The association between TNF-A 
      857TT genotype and gastric cancer was near significant, and may become
      significant if more studies are published.

PMID- 18319719
TI  - Phase I/II study of oxaliplatin with oral S-1 as first-line therapy for patients
      with metastatic colorectal cancer.
AB  - Two phase II studies of S-1 monotherapy have shown promising response rates (RR)
      of 35-40% with good tolerability in patients with untreated metastatic colorectal
      cancer. To investigate the usefulness of S-1 plus oxaliplatin (SOX) as an
      alternative to infusional 5-fluorouracil/leucovorin plus oxaliplatin, the
      recommended dose (RD) of SOX was determined, and its safety and preliminary
      efficacy were evaluated in a phase I/II study. Oxaliplatin was administered at a
      dose of 100 mg m(-2) (level 1) or 130 mg m(-2) (level 2) on day 1, and S-1 (80
      120) was given twice daily for 2 weeks followed by a 1-week rest. This schedule
      was repeated every 3 weeks. Level 2 was determined to be the RD. For the 28
      patients who received the RD, the median treatment course was 6.5 cycles (2-14),
      RR of 50% (1 CR and 13 PR: 95% CI 31-69%), with a median progression-free
      survival of 196 days. Survival rate (1 year) was 79%. Peripheral neuropathy was
      observed in all patients but with no functional disorders. Major grade 3 or 4
      adverse reactions at the RD were neutropaenia (14%), thrombocytopaenia (28%), and
      diarrhoea (3%). SOX regimen is effective and easily manageable without central
      vein access.

PMID- 18319720
TI  - Does smoking among friends explain apparent genetic effects on current smoking in
      adolescence and young adulthood?
AB  - We used data from a prospective cohort study of twins to investigate the
      influence of unmeasured genetic and measured and unmeasured environmental factors
      on the smoking behaviour of adolescents and young adults. Twins were surveyed in
      1988 (aged 11-18 years), 1991, 1996 and 2004 with data from 1409, 1121, 732 and
      758 pairs analysed from each survey wave, respectively. Questionnaires assessed
      the smoking behaviour of twins and the perceived smoking behaviour of friends and
      parents. Using a novel logistic regression analysis, we simultaneously modelled
      individual risk and excess concordance for current smoking as a function of
      zygosity, survey wave, parental smoking and peer smoking. Being concordant for
      having peers who smoked was a predictor of concordance for current smoking
      (P<0.001). After adjusting for peer smoking, monozygotic (MZ) pairs were no more
      alike than dizygotic pairs for current smoking at waves 2, 3 and 4. Genetic
      explanations are not needed to explain the greater concordance for current
      smoking among adult MZ pairs. However, if they are invoked, the role of genes may
      be due to indirect effects acting through the social environment. Smoking
      prevention efforts may benefit more by targeting social factors than attempting
      to identify genetic factors associated with smoking.

PMID- 18319721
TI  - eQED: an efficient method for interpreting eQTL associations using protein
      networks.
AB  - Analysis of expression quantitative trait loci (eQTLs) is an emerging technique
      in which individuals are genotyped across a panel of genetic markers and,
      simultaneously, phenotyped using DNA microarrays. Because of the spacing of
      markers and linkage disequilibrium, each marker may be near many genes making it
      difficult to finely map which of these genes are the causal factors responsible
      for the observed changes in the downstream expression. To address this challenge,
      we present an efficient method for prioritizing candidate genes at a locus. This
      approach, called 'eQTL electrical diagrams' (eQED), integrates eQTLs with protein
      interaction networks by modeling the two data sets as a wiring diagram of current
      sources and resistors. eQED achieved a 79% accuracy in recovering a reference set
      of regulator-target pairs in yeast, which is significantly higher than the
      performance of three competing methods. eQED also annotates 368 protein-protein
      interactions with their directionality of information flow with an accuracy of
      approximately 75%.

PMID- 18319722
TI  - Selection to minimise noise in living systems and its implications for the
      evolution of gene expression.
AB  - Gene expression, like many biological processes, is subject to noise. This noise
      has been measured on a global scale, but its general importance to the fitness of
      an organism is unclear. Here, I show that noise in gene expression in yeast has
      evolved to prevent harmful stochastic variation in the levels of genes that
      reduce fitness when their expression levels change. Therefore, there has probably
      been widespread selection to minimise noise in gene expression. Selection to
      minimise noise, because it results in gene expression that is stable to
      stochastic variation in cellular components, may also constrain the ability of
      gene expression to respond to non-stochastic variation. I present evidence that
      this has indeed been the case in yeast. I therefore conclude that gene expression
      noise is an important biological trait, and one that probably limits the
      evolvability of complex living systems.

PMID- 18319723
TI  - Formulating genome-scale kinetic models in the post-genome era.
AB  - The biological community is now awash in high-throughput data sets and is
      grappling with the challenge of integrating disparate data sets. Such integration
      has taken the form of statistical analysis of large data sets, or through the
      bottom-up reconstruction of reaction networks. While progress has been made with
      statistical and structural methods, large-scale systems have remained refractory
      to dynamic model building by traditional approaches. The availability of
      annotated genomes enabled the reconstruction of genome-scale networks, and now
      the availability of high-throughput metabolomic and fluxomic data along with
      thermodynamic information opens the possibility to build genome-scale kinetic
      models. We describe here a framework for building and analyzing such models. The
      mathematical analysis challenges are reflected in four foundational properties,
      (i) the decomposition of the Jacobian matrix into chemical, kinetic and
      thermodynamic information, (ii) the structural similarity between the
      stoichiometric matrix and the transpose of the gradient matrix, (iii) the duality
      transformations enabling either fluxes or concentrations to serve as the
      independent variables and (iv) the timescale hierarchy in biological networks.
      Recognition and appreciation of these properties highlight notable and
      challenging new in silico analysis issues.

PMID- 18319724
TI  - A systems-level approach to mapping the telomere length maintenance gene
      circuitry.
AB  - The ends of eukaryotic chromosomes are protected by telomeres, nucleoprotein
      structures that are essential for chromosomal stability and integrity.
      Understanding how telomere length is controlled has significant medical
      implications, especially in the fields of aging and cancer. Two recent systematic
      genome-wide surveys measuring the telomere length of deleted mutants in the yeast
      Saccharomyces cerevisiae have identified hundreds of telomere length maintenance
      (TLM) genes, which span a large array of functional categories and different
      localizations within the cell. This study presents a novel general method that
      integrates large-scale screening mutant data with protein-protein interaction
      information to rigorously chart the cellular subnetwork underlying the function
      investigated. Applying this method to the yeast telomere length control data, we
      identify pathways that connect the TLM proteins to the telomere-processing
      machinery, and predict new TLM genes and their effect on telomere length. We
      experimentally validate some of these predictions, demonstrating that our method
      is remarkably accurate. Our results both uncover the complex cellular network
      underlying TLM and validate a new method for inferring such networks.

PMID- 18319725
TI  - A comprehensive modular map of molecular interactions in RB/E2F pathway.
AB  - We present, here, a detailed and curated map of molecular interactions taking
      place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1).
      Deregulations and/or mutations in this pathway are observed in most human
      cancers. The map was created using Systems Biology Graphical Notation language
      with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway
      description format. In the current state the map contains 78 proteins, 176 genes,
      99 protein complexes, 208 distinct chemical species and 165 chemical reactions.
      Overall, the map recapitulates biological facts from approximately 350
      publications annotated in the diagram. The network contains more details about
      RB/E2F interaction network than existing large-scale pathway databases.
      Structural analysis of the interaction network revealed a modular organization of
      the network, which was used to elaborate a more summarized, higher-level
      representation of RB/E2F network. The simplification of complex networks opens
      the road for creating realistic computational models of this regulatory pathway.

PMID- 18319726
TI  - A complete collection of single-gene deletion mutants of Acinetobacter baylyi
      ADP1.
AB  - We have constructed a collection of single-gene deletion mutants for all
      dispensable genes of the soil bacterium Acinetobacter baylyi ADP1. A total of
      2594 deletion mutants were obtained, whereas 499 (16%) were not, and are
      therefore candidate essential genes for life on minimal medium. This essentiality
      data set is 88% consistent with the Escherichia coli data set inferred from the
      Keio mutant collection profiled for growth on minimal medium, while 80% of the
      orthologous genes described as essential in Pseudomonas aeruginosa are also
      essential in ADP1. Several strategies were undertaken to investigate ADP1
      metabolism by (1) searching for discrepancies between our essentiality data and
      current metabolic knowledge, (2) comparing this essentiality data set to those
      from other organisms, (3) systematic phenotyping of the mutant collection on a
      variety of carbon sources (quinate, 2-3 butanediol, glucose, etc.). This
      collection provides a new resource for the study of gene function by forward and
      reverse genetic approaches and constitutes a robust experimental data source for
      systems biology approaches.

PMID- 18319727
TI  - Control of mental activities by internal models in the cerebellum.
AB  - The intricate neuronal circuitry of the cerebellum is thought to encode internal
      models that reproduce the dynamic properties of body parts. These models are
      essential for controlling the movement of these body parts: they allow the brain
      to precisely control the movement without the need for sensory feedback. It is
      thought that the cerebellum might also encode internal models that reproduce the
      essential properties of mental representations in the cerebral cortex. This
      hypothesis suggests a possible mechanism by which intuition and implicit thought
      might function and explains some of the symptoms that are exhibited by
      psychiatric patients. This article examines the conceptual bases and experimental
      evidence for this hypothesis.

PMID- 18319729
TI  - Aspirin resistance is more common in lacunar strokes than embolic strokes and is
      related to stroke severity.
AB  - The aim of this study was to investigate the relationship between aspirin
      resistance, ischaemic stroke subtype, stroke severity, and inflammatory
      cytokines. Aspirin resistance was assessed by thrombelastography in 45 people
      with ischaemic stroke and 25 controls. Plasma interleukin (IL)-6 was measured.
      Stroke severity was assessed using the modified Rankin scale and National
      Institute of Health Stroke Score within 72 h of stroke. Aspirin resistance was
      more common in the stroke than the control group (67% versus 40%, P=0.028), and
      within the stroke group the aspirin-resistant group had a higher Rankin score
      (4.0 versus 2.0, P=0.013). Aspirin resistance was greater in lacunar than embolic
      strokes (platelet activation 79% versus 59%, P=0.020). The stroke aspirin
      resistant group had higher levels of IL-6 than the stroke aspirin-sensitive group
      (2.4+/-1 versus 1.8+/-0.9 ng/mL, P=0.037). Using multivariate analysis, we
      examined the interrelationships between aspirin resistance, IL-6, and stroke
      severity. These analyses showed that IL-6 was independently associated with
      stroke severity as the outcome (B=3.738, P=0.036), and aspirin resistance was
      independently associated with IL-6 (B=0.765, P=0.005) as the outcome. In
      conclusion, aspirin resistance is related to stroke severity and aspirin
      resistance is more common in lacunar strokes than embolic strokes.

PMID- 18319728
TI  - Noise in the nervous system.
AB  - Noise--random disturbances of signals--poses a fundamental problem for
      information processing and affects all aspects of nervous-system function.
      However, the nature, amount and impact of noise in the nervous system have only
      recently been addressed in a quantitative manner. Experimental and computational
      methods have shown that multiple noise sources contribute to cellular and
      behavioural trial-to-trial variability. We review the sources of noise in the
      nervous system, from the molecular to the behavioural level, and show how noise
      contributes to trial-to-trial variability. We highlight how noise affects
      neuronal networks and the principles the nervous system applies to counter
      detrimental effects of noise, and briefly discuss noise's potential benefits.

PMID- 18319730
TI  - Proliferating progenitor cells: a required cellular element for induction of
      ischemic tolerance in the brain.
AB  - Permanent cerebral blood flow reduction results in brain injury (stroke), whereas
      transient ischemic stress results in preconditioning, which can ameliorate the
      extent of irreversible brain injury from subsequent ischemia-the phenomena of
      ischemic tolerance. Neurogenesis in the brain occurs after both ischemic injury
      and the brief ischemia resulting in preconditioning. As neurogenesis is regarded
      as having an intrinsic neuroprotective role in the brain, we investigated the
      possible role of these endogenous progenitor cells in the induction of ischemic
      tolerance. Methylazoxymethanol acetate (MAM) was injected in wild-type mice to
      attenuate precursor cell proliferation and ganciclovir was used to diminish newly
      generated cells in GFAP/HSV-TK mice. Both MAM and ganciclovir significantly
      attenuated ischemia-induced progenitor cell proliferation in the subventricular
      zone, dentate gyrus, penumbra, and corpus callosum as quantified by 5-bromo-2'
      deoxyuridine- or Ki-67-positive cells. Attenuation of ischemia-induced progenitor
      cell proliferation in the brain blocked the induction of ischemic tolerance.
      Further the number of TUNEL (TdT-mediated dUTP nick end labeling)-positive cells
      was considerably increased in MAM-treated animals, whereas MAM did not cause cell
      death in sham-operated controls. The results of this study suggest a role for
      endogenous progenitors in the protective effect of ischemic tolerance.

PMID- 18319731
TI  - Detection of phosphorylated NF-H in the cerebrospinal fluid and blood of
      aneurysmal subarachnoid hemorrhage patients.
AB  - Blood and cerebrospinal fluid (CSF) of 30 Fisher grade 3 aneurysmal subarachnoid
      hemorrhage (ASAH) patients were analyzed for the presence of the phosphorylated
      axonal form of the major neurofilament subunit NF-H (pNF-H), a promising
      biomarker of axonal injury. Patient demographic data including development of
      vasospasm and outcome scores at 6 months after aneurysmal rupture (AR) were
      evaluated. Higher pNF-H blood levels in the first few days after AR were strongly
      predictive of a negative outcome. Blood pNF-H levels in most recovering patients
      showed a steady increase into the second week after AR, presumably reflecting
      axonal degeneration secondary to the original insult. Almost half of the patients
      studied showed sudden dramatic peaks of pNF-H protein release into CSF in the 3-
      to 14-day time period after AR, which must reflect profound, coordinated, and
      secondary loss of axons. Patients in whom vasospasm was detected had
      significantly more pNF-H in both blood and CSF compared with those in whom
      vasospasm was not detected. We conclude that the analysis of pNF-H levels in
      blood and CSF differentiates between patients with poor and favorable outcomes
      and also reveals several novel features of ASAH progression and recovery.

PMID- 18319732
TI  - Endothelial nitric oxide synthase gene single-nucleotide polymorphism predicts
      cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
AB  - Vasospasm is a major cause of morbidity and mortality after aneurysmal
      subarachnoid hemorrhage (aSAH). Studies have shown a link between single
      nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (eNOS)
      gene and the incidence of coronary spasm and aneurysms. Alterations in the eNOS T
      786 SNP may lead to an increased risk of post-aSAH cerebral vasospasm. In this
      prospective clinical study, 77 aSAH patients provided genetic material and were
      followed for the occurrence of vasospasm. In multivariate logistic regression
      analysis, genotype was the only factor predictive of vasospasm. The odds ratio
      (OR) for symptomatic vasospasm in patients with one T allele was 3.3 (95%
      confidence interval (CI): 1.1 to 10.0, P=0.034) and 10.9 for TT. Patients with
      angiographic spasm were 3.6 times more likely to have a T allele (95% CI: 1.3 to
      9.6, P=0.013; for TT: OR 12.6). Patients with severe vasospasm requiring
      endovascular therapy were more likely to have a T allele (OR 3.5, 95% CI: 1.3 to
      9.5, P=0.016; for TT: OR 12.0). Patients with the T allele of the eNOS gene are
      more likely to have severe vasospasm. Presence of this genotype may allow the
      identification of individuals at high risk for post-aSAH vasospasm and lead to
      early treatment and improved outcome.

PMID- 18319733
TI  - Neuroprotective effects of tempol, a catalytic scavenger of peroxynitrite-derived
      free radicals, in a mouse traumatic brain injury model.
AB  - We examined the ability of tempol, a catalytic scavenger of peroxynitrite (PN)
      derived free radicals, to reduce cortical oxidative damage, mitochondrial
      dysfunction, calpain-mediated cytoskeletal (alpha-spectrin) degradation, and
      neurodegeneration, and to improve behavioral recovery after a severe (depth 1.0
      mm), unilateral controlled cortical impact traumatic brain injury (CCI-TBI) in
      male CF-1 mice. Administration of a single 300 mg/kg intraperitoneal dose of
      tempol 15 mins after TBI produced a complete suppression of PN-mediated oxidative
      damage (3-nitrotyrosine, 3NT) in injured cortical tissue at 1 h after injury.
      Identical tempol dosing maintained respiratory function and attenuated 3NT in
      isolated cortical mitochondria at 12 h after injury, the peak of mitochondrial
      dysfunction. Multiple dosing with tempol (300 mg/kg intraperitoneally at 15 mins,
      3, 6, 9, and 12 h) also suppressed alpha-spectrin degradation by 45% at its 24 h
      post-injury peak. The same dosing regimen improved 48 h motor function and
      produced a significant, but limited (17.4%, P<0.05), decrease in hemispheric
      neurodegeneration at 7 days. These results are consistent with a mechanistic link
      between PN-mediated oxidative damage to brain mitochondria, calpain-mediated
      proteolytic damage, and neurodegeneration. However, the modest neuroprotective
      effect of tempol suggests that multitarget combination strategies may be needed
      to interfere with posttraumatic secondary injury to a degree worthy of clinical
      translation.

PMID- 18319734
TI  - Shaping the discussion.

PMID- 18319735
TI  - Forging a proteasome alpha-ring with dedicated proteasome chaperones.

PMID- 18319736
TI  - Ankyrin for methylated lysines.

PMID- 18319737
TI  - A purified catalytically competent spliceosome.

PMID- 18319738
TI  - When a domain is not a domain.

PMID- 18319741
TI  - What is the relevance of determining EGFR-variant-III status in glioblastomas?

PMID- 18319742
TI  - Rates of evolutionary change in viruses: patterns and determinants.
AB  - Understanding the factors that determine the rate at which genomes generate and
      fix mutations provides important insights into key evolutionary mechanisms. We
      review our current knowledge of the rates of mutation and substitution, as well
      as their determinants, in RNA viruses, DNA viruses and retroviruses. We show that
      the high rate of nucleotide substitution in RNA viruses is matched by some DNA
      viruses, suggesting that evolutionary rates in viruses are explained by diverse
      aspects of viral biology, such as genomic architecture and replication speed, and
      not simply by polymerase fidelity.

PMID- 18319743
TI  - Heritability in the genomics era--concepts and misconceptions.
AB  - Heritability allows a comparison of the relative importance of genes and
      environment to the variation of traits within and across populations. The concept
      of heritability and its definition as an estimable, dimensionless population
      parameter was introduced by Sewall Wright and Ronald Fisher nearly a century ago.
      Despite continuous misunderstandings and controversies over its use and
      application, heritability remains key to the response to selection in
      evolutionary biology and agriculture, and to the prediction of disease risk in
      medicine. Recent reports of substantial heritability for gene expression and new
      estimation methods using marker data highlight the relevance of heritability in
      the genomics era.

PMID- 18319744
TI  - Measurements of the atmospheric carbon monoxide column with a ground-based length
      modulated radiometer.
AB  - A ground-based remote sounding instrument that uses a length-modulated radiometer
      to measure the total atmospheric carbon monoxide (CO) column has been built.
      Measurements made in Toronto during August and September of 1994 showed average
      CO concentrations of 125 to 150 parts per billion in volume (ppbv, parts in
      10(9)). Similar measurements made in October at a rural site 80 km north of
      Toronto showed concentrations of approximately 100 ppbv. The latter measurements
      are shown to agree with other simultaneous ground- and satellite-based
      measurements. This instrument is an advanced prototype of the MOPITT
      (Measurements of Pollution in the Troposphere) satellite instrument.

PMID- 18319745
TI  - Transient behavior of infrared photoconductors: application of a numerical model.
AB  - A numerical model for the transient response of extrinsic photoconductors is
      applied to the behavior of Ge:Ga and GaAs:Te detectors. Photoconductors display a
      two-component response to changes in illumination. The characteristic time and
      magnitude for the slow component have been studied as a function of background
      flux, applied field, temperature, device length, and signal size. For large
      signal applications, the background flux affects the transient response even when
      the signal is orders of magnitude greater than the background. Experimental
      results are presented to support key predictions of the modeling. Because the
      ratio of fast to slow components is independent of both background and signal
      size, we propose the operation of detectors in such a way that final signal
      levels are derived from the fast component.

PMID- 18319746
TI  - Normal-incidence efficiencies of 4800-grooves/mm-ruled replica gratings with
      multilayer and gold coatings in the 125-325-A wavelength region.
AB  - The normal-incidence efficiencies of two 4800-grooves/mm ruled replica gratings,
      one with a dual-bandpass molybdenum/silicon multilayer coating and the other with
      a gold coating, were measured by use of synchrotron radiation in the 125-325-A
      wavelength region. The peak reflectance of the multilayer coating was 22% in the
      first Bragg order near 235 A and 28% in the second Bragg order near 126 A. The
      peak efficiency of the multilayer grating was 2.6% in the first diffraction order
      near 225 A and 0.3% in the second diffraction order near 125 A. The efficiencies
      of the multilayer grating were much higher than the corresponding efficiencies of
      the gold grating. The characterization of the surfaces of the gratings by atomic
      force microscopy indicated rms microroughness values in the 5-18-microm(-1)
      frequency range of 12-20 A for the multilayer grating and 22-32 A for the gold
      grating. Both gratings had bumpy surface features larger than the nominal groove
      height. The rather large surface roughness and groove irregularities had a
      detrimental effect on the grating efficiencies.

PMID- 18319747
TI  - Fiber-optic voltage sensor for SF6 gas-insulated high-voltage switchgear.
AB  - We present an optical-fiber voltage sensor for 170-kV gas-insulated high-voltage
      switchgear. The sensor is based on the converse piezoelectric effect of quartz.
      The full voltage is applied to a cylinder-shaped quartz crystal. The resulting
      alternating piezoelectric deformation of the crystal is sensed by an elliptical
      core dual-mode fiber, which is wound onto the circumferential crystal surface.
      The fiber is interrogated by low-coherence interferometry. We address the
      dielectric design of the sensor and verify its dielectric reliability under ac
      overvoltages and lightning impulse voltages. We then investigate the sensor
      performance, including accuracy, dynamic range, bandwidth, and temperature
      dependence.

PMID- 18319748
TI  - Phase unwrapping through demodulation by use of the regularized phase-tracking
      technique.
AB  - Most interferogram demodulation techniques give the detected phase wrapped owing
      to the arctangent function involved in the final step of the demodulation
      process. To obtain a continuous detected phase, an unwrapping process must be
      performed. Here we propose a phase-unwrapping technique based on a regularized
      phase-tracking (RPT) system. Phase unwrapping is achieved in two steps. First, we
      obtain two phase-shifted fringe patterns from the demodulated wrapped phase (the
      sine and the cosine), then demodulate them by using the RPT technique. In the RPT
      technique the unwrapping process is achieved simultaneously with the demodulation
      process so that the final goal of unwrapping is therefore achieved. The RPT
      method for unwrapping the phase is compared with the technique of least-squares
      integration of wrapped phase differences to outline the substantial noise
      robustness of the RPT technique.

PMID- 18319749
TI  - Two-dimensional restoration of motion-degraded intensified CCD imagery.
AB  - A Wiener filter-based deconvolution algorithm is developed to restore vibration
      degraded video imagery from an intensified CCD camera. The method is based on the
      use of azimuth and elevation angular optical line-of-sight data recorded from
      external sensors to estimate a two-dimensional vibration-blur impulse response on
      a per frame basis. Flight conditions are reproduced in the laboratory by use of
      prerecorded in-flight vibration data. The performance of the algorithm varies
      from frame to frame, following the time-varying characteristics of the vibration
      blur impulse response. However, real-time display of the restored video minimizes
      these effects because of eye integration, and near-full restoration of the
      original uncorrupted imagery is observed for both high-light- and low-light-level
      conditions with minimal amplification of noise.

PMID- 18319750
TI  - Polarimetric distributed feedback fiber laser sensor for simultaneous strain and
      temperature measurements.
AB  - We report the application of a dual polarization distributed feedback (DFB) fiber
      laser as a strain and temperature sensor. By measurement of the absolute
      wavelength of one polarization as well as the polarization beat frequency, strain
      and temperature were determined simultaneously. The sensor has an accuracy of +3
      microepsilon and +/-0.04 degrees C. Self-heating of the DFB fiber laser as a
      function of pump power was measured with this sensor.

PMID- 18319751
TI  - Measurement of changes in optical path length and reflectivity with phase
      shifting laser feedback interferometry.
AB  - The operating characteristics of a novel phase-shifting interferometer are
      presented. Interference arises by reflecting the light from a sample back into
      the cavity of a cw He-Ne laser. Changes in phase and fringe visibility are
      calculated from an overdetermined set of phase-shifted intensity measurements
      with the phase shifts being introduced with an electro-optic modulator. The
      interferometer is sensitive enough to measure displacements below 1 Hz with a rms
      error of approximately 1 nm from a sample that reflects only 3% of the 28 microW
      that is incident on its surface. The interferometer is applied to the
      determination of cantilever bending of a piezoelectric bimorph.

PMID- 18319752
TI  - Simultaneous measurement of velocity and length of moving surfaces by a speckle
      velocimeter with two self-mixing laser diodes.
AB  - A novel laser speckle velocimeter with two self-mixing laser diodes (SM-LD's) for
      velocity and length measurements of moving surfaces is reported. The mean
      frequency of the speckle signal obtained in the measurement system depends on the
      surface path illuminated by the SM-LD. This behavior of the speckle signal in the
      SM-LD's is exploited to detect the front and the end edges of a target surface by
      sampling continuously the number of intensity changes in a speckle signal
      waveform. Once the edges are determined, the velocity and the length of the
      surface are calculated easily. The error for length and velocity measurements of
      a target with a homogeneous rough plane surface of 60-mm length, moving at a
      velocity of 200 mm/s, can be as low as 2.1% and 1.75%, respectively.

PMID- 18319753
TI  - Photopolarimetric measurement of single, intact pulp fibers by mueller matrix
      imaging polarimetry.
AB  - A method based on Mueller matrix polarimetry is developed and demonstrated for
      determining the fibril angle and relative phase retardation of single, intact
      pulp fibers. The method permits quantitative and nondestructive determination of
      these parameters from measurements at one wavelength without any fiber alignment.
      The Mueller matrix of a pulp fiber and its relationship with the fibril angle and
      phase retardation are described. A nonmodulation method for determining the
      Mueller matrix is then proposed that is based on a set of intensity data
      registered by a single detector. Measurements were carried out with single pulp
      fibers as samples to test the theoretical prediction. The test measurements and
      results are described and presented.

PMID- 18319754
TI  - White-light performance of a polarization-independent liquid-crystal phase
      modulator.
AB  - The broadband performance of a polarization-insensitive liquid-crystal phase
      modulator is analyzed, and its effect on an adaptive optics system is quantified.

PMID- 18319755
TI  - Measurement of shape by using projected random patterns and temporal digital
      speckle photography.
AB  - Projected random patterns have been used to measure the shape of discontinuous
      objects. A sequence of independent random patterns are projected onto the object.
      These images are analyzed by use of the technique called temporal digital speckle
      photography (DSP) that is introduced here. With temporal DSP the spatial
      resolution of the shape measurement is improved considerably compared with
      previously reported results with projected random patterns. A calibration
      procedure is described that uses a sequence of independent random patterns to
      calibrate measurement volume. As a result, independent space coordinates for each
      subimage are obtained. The accuracy is of the order of 1/1000 of the field of
      view where a subimage size of 8 pixels seems to be a good compromise between
      reliability and spatial resolution. The technique is illustrated with a
      measurement of an electrical plug and a 9-V battery.

PMID- 18319756
TI  - Errors of temperature measurement with multiband infrared systems.
AB  - A model of the errors of temperature measurement with multiband systems was
      developed. Calculations of these errors for some measurement conditions and
      systems were carried out. It was shown that multiband systems are capable of
      producing accurate results of noncontact temperature measurement only in a
      limited number of applications and that to have small internal errors, they must
      be designed and built with much greater care than in the case of typical single
      band systems.

PMID- 18319757
TI  - Spectrophotometer spectral bandwidth calibration with absorption bands crystal
      standard.
AB  - A procedure for calibration of a spectral bandwidth standard for high-resolution
      spectrophotometers is described. Symmetrical absorption bands for a crystal
      standard are adopted. The method relies on spectral band shape fitting followed
      by a convolution with the slit function of the spectrophotometer. A reference
      spectrophotometer is used to calibrate the spectral bandwidth standard. Bandwidth
      calibration curves for a minimum spectral transmission factor relative to the
      spectral bandwidth of the reference spectrophotometer are derived for the
      absorption bands at the wavelength of the band absorption maximum. The family of
      these calibration curves characterizes the spectral bandwidth standard. We
      calibrate the spectral bandwidth of a spectrophotometer with respect to the
      reference spectrophotometer by determining the spectral transmission factor
      minimum at every calibrated absorption band of the bandwidth standard for the
      nominal instrument values of the spectral bandwidth. With reference to the
      standard spectral bandwidth calibration curves, the relation of the spectral
      bandwidth to the reference spectrophotometer is determined. We determine the
      discrepancy in the spectrophotometers' spectral bandwidths by averaging the
      spectral bandwidth discrepancies relative to the standard calibrated values found
      at the absorption bands considered. A weighted average of the uncertainties is
      taken.

PMID- 18319758
TI  - Stability improvements for an interferometer through study of spectral
      interference patterns.
AB  - Conventional Mach-Zehnder interferometer configuration is modified to enhance its
      stability from the vibrations. To study the effects of vibrations on the Mach
      Zehnder interferometer, we used spectral interference fringes from a broadband
      nanosecond dye laser source. We observed an improvement in the stability of the
      interferometer by a factor of 3.

PMID- 18319759
TI  - Absolute measurement of planarity with Fritz's method: uncertainty evaluation.
AB  - Fritz's method [Opt. Eng. 23, 379 (1984)] of using Zernike polynomials to assess
      the absolute planarity of test plates is revisited. A refinement is described
      that takes into account the data decorrelation that appears in experiments. An
      uncertainty balance is defined by propagation of error contributions through the
      steps of the method. The resultant measuring procedure is demonstrated on a data
      set from experiments, and a nanometer level of uncertainty is achieved.

PMID- 18319760
TI  - Differential equation for normal glass dispersion and evaluation of the secondary
      spectrum.
AB  - Some of the questions concerning secondary chromatic aberration at both sides of
      the visible band of the spectrum are the following: (1) What is the bandwidth at
      different wavelengths, given the permissible chromatic aberration circle and the
      lens aperture? (2) What is the size of the chromatic aberration circle, given the
      wavelength, the bandwidth, and the lens aperture? The answers to these and other
      questions may be found with the new definitions of V-number and relative partial
      dispersion P based on infinitesimal bandwidths that we propose. In addition, an
      alignment chart for the secondary color of a normal glass doublet is presented,
      so fast answers to the questions posed above and to other questions concerned
      with secondary color can be found. In addition, a continual challenge in computer
      aided lens design is the use of optical glasses as design parameters in
      simultaneous optimization of lens systems over various regions of the spectrum.
      This problem could be solved if we could find an ideal glass family, not too
      different from real glasses, such that, given the refractive index n and the V
      number at any wavelength, the indices at all wavelengths could be determined.
      Therefore we derive a differential equation for normal glass dispersion and
      present a recursive solution.

PMID- 18319761
TI  - Modulation transfer function measurements of microjetted microlenses.
AB  - We measured the modulation transfer function for microjetted microlenses with
      diameters ranging between 109 and 400 microm and with focal lengths ranging
      between 135 and 540 microm. We found that single-drop 109-microm-diameter
      microlenses perform close to their theoretical cutoff frequency. However, the
      larger lenses made with multiple droplets have a cutoff frequency that is 35% of
      the theoretical value. We interpret this as an illustration of the rapid increase
      in spherical aberration as the diameter of a lens increases.

PMID- 18319762
TI  - Small optical magnetic-field sensor that uses rare-Earth iron garnet films based
      on the faraday effect.
AB  - Highly accurate optical magnetic-field probe sensors that use iron garnet films
      have been developed. New probe-type sensors were designed with a confocal optical
      system. A new garnet composition,
      Bi(0.98)Gd(0.92)La(0.03)Y(1.07)Fe(4.72)Ga(0.28)O(12), was found that shows high
      temperature stability for a sensitivity of less than 2.0% from -20 to +80 degrees
      C. The linearity error of the sensor output was within 1.0% for alternating
      magnetic fields from 0.3 to 42 mT. An optical current transformer that uses the
      proposed sensor has an ac linearity of 1.0% for input current up to nearly 300 A.
      The sensor realized high performance in actual use.

PMID- 18319763
TI  - Simple expressions for transmission and reflection matrix elements of a biaxial
      thin layer at normal incidence.
AB  - The extended Jones matrix method is applied for determination of the transmission
      and reflection matrices for a normally incident plane wave upon an homogeneous
      and lossless biaxial thin layer. The elements of these matrices are expressed by
      simple analytical relations. By using these relations one can express
      analytically the polarization-dependent optical parameters to be determined by
      generalized ellipsometry.

PMID- 18319764
TI  - Photon cross-correlation spectroscopy to 10-ns resolution.
AB  - We describe a low-cost modification based on the research of Arecchi et al. [Opt.
      Commun. 3, 284-288 (1971)] on a standard photon correlation spectroscopy setup
      for measuring small (approximately equal 1%) and fast (resolution, approximately
      equal 10 ns) light fluctuations. Details of the electronics and optics permit the
      apparatus to be easily reproduced. Careful tests show that spurious correlations
      of <or=1% can be achieved with standard detectors only when taking precautions
      with the electronics. Moreover, measurements on latex spheres, ellipsoids, and
      protein solutions show that fast and very small light fluctuations (
      approximately equal 1-5%) can be studied versus scattering vector and light
      polarization.

PMID- 18319765
TI  - Determination of Kubelka-Munk scattering and absorption coefficients by diffuse
      illumination.
AB  - The Kubelka-Munk theory, although it provides an equation that relates the
      reflection of a sample under diffuse illumination to certain of its properties,
      does not take boundary reflectance into account. Boundary reflection is always
      present because there is always a difference between the refractive indices of
      the sample and of the surrounding medium. We describe how a half-sphere is used
      to achieve diffuse illumination, and we present and exemplify equations that
      correct for boundary reflection with measurements of four composite restorative
      dental materials. The refractive index of the sample is measured with a matching
      technique that employs a glycerol-water mixture. Edge loss errors are estimated.

PMID- 18319766
TI  - Interference coatings based on synthesized silicon nitride.
AB  - Silicon nitrides are synthesized by ion-assisted deposition with only one coating
      material and a nitrogen-ion-beam source. All the SiN(x) films are amorphous and
      mechanically strong. A wide range of refractive indices from 3.43 to 1.72 at a
      wavelength of 1550 nm is obtained. Near-IR antireflection coating and a bandpass
      filter based on the multilayers of SiN(x) and Si are demonstrated.

PMID- 18319767
TI  - Layer thickness fluctuations in optical coatings with non-quarter-wave design.
AB  - Previous research on highly reflective multilayer optical coatings has shown that
      varying the thickness of layers from their traditional quarter-wave values gives
      the potential for greater damage thresholds without sacrificing the desired
      optical properties. We numerically investigate the influence of unintended layer
      thickness fluctuations in these nontraditional designs, concluding that such
      fluctuations should have minimal effect on the optical properties of the coating.
      This result makes the prospect of producing nontraditional designs more
      promising.

PMID- 18319768
TI  - Cone prism: principles of optical design and linear measurement of the
      applanation diameter or area of the cornea.
AB  - The cone prism introduced is mainly used in applanation tonometers to act as an
      applanation prism for linear measurement of the applanation diameter or the
      applanation area of the cornea. Its principles of optical design and linear
      measurement are expounded in detail. The measuring body, which comprises the cone
      prism and other optical and electronic parts, is also briefly introduced.

PMID- 18319769
TI  - Characterization of dentin and enamel by use of optical coherence tomography.
AB  - Optical coherence tomographic images of human dentin and enamel are obtained by
      use of polarization-sensitive optical coherence tomography. A birefringence
      effect in enamel (lambda = 856 nm) and light propagation along dentinal tubules
      are observed. The group index of refraction for both dentin and enamel was
      measured at 1.50 +/- 0.02 and 1.62 +/- 0.02, respectively.

PMID- 18319770
TI  - Evaluation of optical coherence quantitation of analytes in turbid media by use
      of two wavelengths.
AB  - We introduce a novel method for determining analyte concentration as a function
      of depth in a highly scattering media by use of a dual-wavelength optical
      coherence tomography system. We account for the effect of scattering on the
      measured attenuation by using a second wavelength that is not absorbed by the
      sample. We assess the applicability of this technique by measuring the
      concentration of water in an Intralipid phantom, using a probe wavelength of 1.53
      microm and a reference wavelength of 1.31 microm. The results of our study show a
      strong correlation between the measured absorption and the water content of the
      sample. The accuracy of the technique, however, was limited by the dominance of
      scattering over absorption in the turbid media. Thus, although the effects of
      scattering were minimized, significant errors remained in the calculated
      absorption values. More-accurate results could be obtained with the use of more
      powerful superluminescent diodes and a choice of wavelengths at which absorption
      effects are more significant relative to scattering.

PMID- 18319771
TI  - Video-rate confocal scanning laser microscope for imaging human tissues in vivo.
AB  - We have built a video-rate confocal scanning laser microscope for reflectance
      imaging of human skin and oral mucosa in vivo. Design and imaging parameters were
      determined for optimum resolution and contrast. Mechanical skin-holding fixtures
      and oral tissue clamps were made for stable objective lens-to-tissue contact such
      that gross tissue motion relative to the microscope was minimized. Confocal
      imaging was possible to maximum depths of 350 microm in human skin and 450 microm
      in oral mucosa, with measured lateral resolution of 0.5-1 microm and axial
      resolution (section thickness) of 3-5 microm at the 1064-nm wavelength. This
      resolution is comparable with that of conventional microscopy of excised biopsies
      (histology). Normal and abnormal tissue morphology and dynamic processes were
      observed.

PMID- 18319772
TI  - Noise analysis of a combined optical coherence tomograph and a confocal scanning
      ophthalmoscope.
AB  - A fiberized optical coherence tomographic (OCT) system is modified to produce a
      confocal image similar to that produced by a scanning laser ophthalmoscope. Two
      possible configurations are presented, one that can deliver either an OCT or a
      confocal image and another that is capable of producing both the OCT and the
      confocal images simultaneously. Using the later configuration, we demonstrate
      such images from the retina in the living eye. The penalty in terms of
      performance reduction introduced into the optical coherence tomograph when
      integrated with a confocal receiver and the signal-to-noise ratio analysis for
      the different confocal receiver configurations are presented.

PMID- 18319773
TI  - Experimental and theoretical laser-Doppler frequency spectra of a tissuelike
      model of a human head with capillaries.
AB  - Laser-Doppler flow measurements with penetration depths from 10 to 30 mm have
      been performed on a layered model of the human head consisting of a regular array
      of capillaries with diameters of 340 microm embedded in an epoxy matrix with
      tissuelike scattering and absorption properties. Monte Carlo simulations and an
      analytical approach based on diffusing wave spectroscopy have corroborated the
      measurements and have led to a quantitative description of flow in deep-lying
      tissue layers with regard to layers near the surface also. The results indicate
      that it may be possible to measure changes in cortical blood flow even in the
      presence of a well-perfused scalp.

PMID- 18319774
TI  - Biomedical optical tomography using dynamic parameterization and bayesian
      conditioning on photon migration measurements.
AB  - Stochastic reconstruction techniques are developed for mapping the interior
      optical properties of tissues from exterior frequency-domain photon migration
      measurements at the air-tissue interface. Parameter fields of absorption cross
      section, fluorescence lifetime, and quantum efficiency are accurately
      reconstructed from simulated noisy measurements of phase shift and amplitude
      modulation by use of a recursive, Bayesian, minimum-variance estimator known as
      the approximate extended Kalman filter. Parameter field updates are followed by
      data-driven zonation to improve the accuracy, stability, and computational
      efficiency of the method by moving the system from an underdetermined toward an
      overdetermined set of equations. These methods were originally developed by
      Eppstein and Dougherty [Water Resources Res. 32, 3321 (1996)] for applications in
      geohydrology. Estimates are constrained to within feasible ranges by modeling of
      parameters as beta-distributed random variables. No arbitrary smoothing,
      regularization, or interpolation is required. Results are compared with those
      determined by use of Newton-Raphson-based inversions. The speed and accuracy of
      these preliminary Bayesian reconstructions suggest the near-future application of
      this inversion technology to three-dimensional biomedical imaging with frequency
      domain photon migration.

PMID- 18319776
TI  - Fast simulation of a kolmogorov phase screen.
AB  - A previously presented method for modeling Kolmogorov phase fluctuations over a
      finite aperture is both formalized and improved on. The method relies on forming
      an initial low-resolution Kolmogorov phase screen from direct factorization of a
      covariance. The resolution of the screen is then increased by a randomized
      interpolation to produce a Kolmogorov phase screen of the desired size. The
      computational requirement is asymptotically proportional to the number of points
      in the phase screen.

PMID- 18319777
TI  - Subwavelength-resolvable focused non-gaussian beam shaped with a binary
      diffractive optical element.
AB  - The diffraction-limited spot size limits the optical disk storage capacity and
      microscopic resolution. We describe a technique to shape a focused Gaussian beam
      into a superresolving beam by using a diffractive optical element fabricated by
      laser-assisted chemical etching. The focused shaped beam has a smaller width and
      a longer depth of focus than a similarly focused Gaussian beam. Using the
      diffraction-limited shaped beam along with threshold writing, we achieved a
      written pit size of less than 0.33 microm at a 695-nm laser wavelength, compared
      with a 0.7-microm focused Gaussian spot size (full width at e(-2) of the peak)
      with the same focusing lens. The energy conversion efficiency for the beam
      shaping was approximately 81%.

PMID- 18319778
TI  - Polarization multiplexing of diffractive elements with metal-stripe grating
      pixels.
AB  - Diffractive elements with polarization multiplexing for the visible spectral
      region are demonstrated. The polarization-multiplexing property of the element is
      based on the polarization-dependent transmission characteristics of metal-stripe
      subwavelength period gratings. The proper dimensions of these gratings are
      estimated by rigorous calculations. The principle of polarization multiplexing by
      use of metal-stripe subwavelength period gratings is described for a diffractive
      element that has a binary amplitude transmission per polarization channel and is
      demonstrated by experimental results.

PMID- 18319779
TI  - Morphologically preprocessed joint transform correlation.
AB  - A morphologically preprocessed joint transform correlation is proposed that
      combines the techniques of morphological filtering and joint transform
      correlation. We improve on the performance of a joint transform correlator by
      eliminating noise with morphological preprocessing and by performing edge
      detection of input images. Computer simulation results show that the
      corresponding system contributes to a better discrimination capability than
      gradient operator-based and wavelet-based preprocessed joint transform
      correlation.

PMID- 18319780
TI  - Computer-generated holograms to produce high-density intensity patterns.
AB  - A computer-generated hologram consisting of N x N resolution cells produces a
      reconstructed image consisting of N x N sampling points. Since the width of the
      primary peaks in the point-spread function is twice the pitch of the sampling
      points, the intensity at intermediate points between the sampling points depends
      on the interference between the sampling points. Carefully controlling the
      complex amplitudes of the sampling points makes it possible to control the
      intensity not only at the sampling points but also at the intermediate points;
      the intensity of the reconstructed image can be controlled at 2N x 2N points.
      Preliminary experiments demonstrating the generation of high-density intensity
      patterns were performed.

PMID- 18319781
TI  - Electronic channel fringe holography for depth and delay measurements.
AB  - Electronic spectral holography in the form developed by Shih [Ph.D. dissertation,
      University Microfilms, Ann Arbor, Mich. (1995)] is adapted to various
      applications, including optical coherence tomography in scattering media,
      contouring of surfaces, and optical fiber mode examination.

PMID- 18319782
TI  - Fast numerical reconstruction technique for high-resolution hybrid holographic
      microscopy.
AB  - A numerical reconstruction method believed to be new is proposed for hybrid
      holographic microscopy in which the hologram of a microscopic object is recorded
      by an image sensor and is then reconstructed by a computer. Because the Fresnel
      Kirchhoff integral must be used for numerical reconstruction to achieve high
      resolution, we propose an approximation technique for reducing the calculation
      time. This approximation technique is suitable for microscopic application. The
      numerical reconstruction of 1-microm-sized objects was demonstrated with a He-Ne
      laser (lambda = 0.6328 microm).

PMID- 18319783
TI  - Simple model for image-plane polychromatic speckle contrast.
AB  - A simple geometrical model was developed for calculation of the contrast of a
      polychromatic image-plane speckle pattern from a source of light with high
      spatial coherence. It is based on counting the number of independent speckle
      patterns that contribute to a given point in the image plane. This results in a
      simple equation for the contrast as a function of imaging geometry; relative
      orientation of the projection direction, observation direction, and specimen
      normal; bandwidth of the light source; and surface roughness. Its validity was
      established by comparison with an exact solution: rms errors in the calculated
      contrast were only 0.033 over a wide range of parameter values likely to be
      encountered in practice.

PMID- 18319784
TI  - Two-dimensional measurement technique for birefringence vector distributions:
      data processing and experimental verification.
AB  - A two-dimensional measurement method for a birefringence vector distribution
      differs from a point-measurement method not only in the two-dimensional system
      nonuniformity but also in the system reliability. The previously proposed
      intrinsic vector allowed for the elimination of the influence of the system
      nonuniformity, whereas the two-dimensional system reliability is ensured by both
      an online diagnosis technique and an image lock-in processing. It is revealed
      that the measured intrinsic vector is relevant not only with the birefringence
      vector distribution in a sample but also with the natural birefringence vector
      distributions that exist in the optic components. The complete solution from the
      measured intrinsic vector results in a bidirectional vector for the desired
      birefringence vector distribution. The correctness of the two-dimensional
      measurement principle is examined by means of a comparison of the measured data
      with that calculated from a finite-element analysis based on the photoelastic
      effect.

PMID- 18319785
TI  - Two-dimensional measurement technique for birefringence vector distributions:
      measurement principle.
AB  - The two-dimensional measurement principle for a birefringence vector distribution
      in transparent materials is analyzed. The system nonuniformity that results from
      the system components makes the two-dimensional measurement principle quite
      different from that of a point-measurement method, and the measurement principle
      requires a two-dimensional analysis. A pulsed optical phase modulation is
      employed to simplify the two-dimensional mathematical analysis. As a result,
      concepts are proposed of the system function that characterizes the system
      nonuniformity that results from the system components and of the intrinsic
      function that is related to the birefringence vector distribution in a
      birefringent sample. The influence of the system nonuniformity on the two
      dimensional measurement is eliminated by measurement of the intrinsic function,
      whereas its two values allow for the mathematical separation of the birefringence
      vector components. The effectiveness of the two-dimensional analysis is
      illustrated by measurement of a birefringence vector distribution, which is
      induced by an internal stress distribution in a poly(methyl methacrylate) plate,
      owing to the photoelastic effect.

PMID- 18319786
TI  - Regularization of the image division approach to blind deconvolution.
AB  - A problem of blind deconvolution arises when one attempts to restore a short
      exposure image that has been degraded by random atmospheric turbulence. We attack
      the problem by using two short-exposure images as data inputs. The Fourier
      transform of each is taken, and the two are divided. The result is the quotient
      of the two unknown transfer functions. The latter are expressed, by means of the
      sampling theorem, as Fourier series in corresponding point-spread functions, the
      unknowns of the problem. Cross multiplying the division equation gives an
      equation that is linear in the unknowns. However, the problem has, initially, a
      multiplicity of solutions. This deficiency is overcome by use of the prior
      knowledge that the object and the point-spread functions have finite (albeit
      unknown) support extensions and also are positive. The result is a fixed-length,
      linear algorithm that is regularized to the presence of 4-15% additive noise of
      detection.

PMID- 18319787
TI  - Electronic and optical moi? Interference with microchannel plates: artifacts and
      benefits.
AB  - The spatial resolution of position-sensitive detectors that use stacks of
      microchannel plates (MCP's) with high-resolution anodes can be better than 20
      microm FWHM [Proc. SPIE 3114, 283-294 (1997)]. At this level of accuracy, channel
      misalignments of the MCP's in the stack can cause observable moire interference
      patterns. We show that the flat-field detector response can have moire beat
      pattern modulations of as great as approximately 27% with periods from as small
      as a few channel diameters to as great as the size of a MCP multifiber. These
      modulations, however, may be essentially eliminated by rotation of the MCP's or
      by a mismatch of the channel sizes. We also discuss how the modulation phenomena
      can be a useful tool for mapping the metric nonlinearities of MCP detector
      readout systems. Employing the optical moire effect, we demonstrate a simple, but
      effective, technique for evaluation of geometrical deformations simultaneously
      over a large MCP area. For a typical MCP, with a 60-channel-wide multifiber, we
      can obtain accuracies of 1.2 mrad for multifiber rotations and twists and
      35/(L/p) mrad for channel-long axis distortions (where L/p is MCP thickness to
      interchannel distance ratio). This technique may be used for the development of
      MCP x-ray optics, which impose tight limitations on geometrical distortions,
      which in turn are not otherwise easily measurable with high accuracy.

PMID- 18319788
TI  - Joint processing of hartmann sensor and conventional image measurements to
      estimate large aberrations: theory and experimental results.
AB  - We report experimental results for what we believe to be a new technique for
      estimating aberrations that extends the strength of an aberration that may be
      sensed with Hartmann sensor technology by means of an algorithm that processes
      both a Hartmann sensor image and a conventional image formed with the same
      aberration. We find that the theory and the experiment match well within the
      experimental error and that strong defocus aberrations can be accurately sensed
      with this technique.

PMID- 18319789
TI  - Complex phase tracing method for fringe pattern analysis.
AB  - We present what we believe to be a novel complex phase tracing method for fringe
      pattern analysis related to the phase-locked loop idea. The image with deformed
      complex fringes is analyzed with lexicographic scansion that leads directly to
      the investigated phase without unwrapping. Robustness of the procedure is ensured
      by the delay mechanism in the process of calculating the reference value. A
      numerical model and examples of application of the presented method are given.

PMID- 18319790
TI  - Application of multiframe high-resolution image reconstruction to digital
      microscopy.
AB  - A high-resolution image reconstruction algorithm previously used to improve
      undersampled infrared airborne imagery was applied to two different sets of
      digital microscopy images. One set is that of medical pap smear images, and the
      second set contains metallurgical micrographs. Both the pap smear images and the
      metallurgical micrographs are undersampled, thus causing loss of detail and
      aliasing artifacts. The algorithm minimizes the effects of aliasing and restores
      detail unobtainable through simple interpolation techniques. Both applications
      demonstrate improvement by use of the image reconstruction algorithm.

PMID- 18319791
TI  - Demonstration and architectural analysis of complementary metal-oxide
      semiconductor /multiple-quantum-well smart-pixel array cellular logic processors
      for single-instruction multiple-data parallel-pipeline processing.
AB  - We present an optoelectronic-VLSI system that integrates complementary metal
      oxide semiconductor/multiple-quantum-well smart pixels for high-throughput
      computation and signal processing. The system uses 5 x 10 cellular smart-pixel
      arrays with intrachip electrical mesh interconnections and interchip optical
      point-to-point interconnections. Each smart pixel is a fine grain microprocessor
      that executes binary image algebra instructions. There is one dual-rail optical
      modulator output and one dual-rail optical detector input in each pixel. These
      optical input-output arrays provide chip-to-chip optical interconnects. Cascading
      these smart-pixel array chips permits direct transfer of two-dimensional data or
      images in parallel. We present laboratory demonstrations of the system for
      digital image edge detection and digital video motion estimation. We also analyze
      the performance of the system compared with that of conventional single
      instruction-multiple-data processors.

PMID- 18319792
TI  - Tolerance of optical interconnections to misalignment.
AB  - The fundamental reasons that determine the tolerance of free-space optical
      interconnect systems to misalignment are considered. By evaluation of the overlap
      of single-mode optical beams in the presence of misalignment it possible to
      determine an optimum beam configuration. It is shown that for any level of
      misalignment there is an optimum beam diameter that maximizes the coupling of
      light through the system. Many interconnect systems are not single mode
      throughout, so the analysis is extended to cover multimode systems. It is shown
      that, in principle, any level of misalignment can be accommodated by use of
      multimode beams, although at the cost of reduced channel density. It is shown
      that the presence of misalignment will mean that the number of channels that can
      be supported by an interconnect reduces with the length of the interconnect. As
      possible candidates for passively aligned systems, three example optical systems
      are analyzed by use of the methods developed.

PMID- 18319793
TI  - Free-space optical relay for the interconnection of multimode fibers.
AB  - We present results from a system that shows that multimode fibers can be used for
      both the input and the output of a free-space optical system. The system consists
      of plastic microlenses integrated with plastic optomechanical components that are
      suitable for low-cost fabrication and assembly. Such a system opens up
      opportunities to construct large repeaters and switches for multigigabit ethernet
      applications by integration with two-dimensional arrays of optoelectronic
      devices. We demonstrate a 2.5-Gbit/s transmission rate by using commercial
      vertical-cavity surface-emitting lasers coupled to 62.5-microm core fibers. We
      consider the design constraints and the capabilities of custom optical modules
      suitable for mass production.

PMID- 18319794
TI  - Optical tunneling effect calculation of a solid immersion lens for use in optical
      disk memory.
AB  - A solid immersion lens (SIL) has the advantage of easily decreasing the spot size
      for high data density in optical recording. To accurately obtain the optical
      tunneling effect for a high-N.A. SIL, we calculated the optical tunneling beam
      characteristics, using electromagnetic theory. Tunneling beam spot-size
      dependence on polarization direction and energy-transfer efficiency are also
      clearly shown.

PMID- 18319795
TI  - Etching and printing of diffractive optical microstructures by a femtosecond
      excimer laser.
AB  - Diffractive optics fabrication is performed by two complementary processing
      methods that rely on the photoablation of materials by ultrashort UV laser
      pulses. The spatially selective ablation of materials permits the direct
      microetching of high-quality surface-relief patterns. In addition, the direct,
      spatially selective transfer of the ablated material onto planar and nonplanar
      receiving substrates provides a complementary microprinting operation. The
      radiation from the ultrashort pulsed excimer laser results in superior quality at
      relatively low-energy density levels, owing to the short absorption length and
      minimal thermal-diffusion effects. Computer-generated holographic structures are
      produced by both modes of operation. Submicrometer features, including Bragg-type
      structures, are microprinted onto planar and high-curvature optical-fiber
      surfaces, demonstrating the unique ability of the schemes for complex
      microstructure and potentially nanostructure development.

PMID- 18319796
TI  - Synchronous amplitude and time control for an optimum dynamic range variable
      photonic delay line.
AB  - A synchronous-amplitude-controlled and time-delay-controlled photonic controller
      for phased-array antenna applications is proposed and demonstrated. Amplitude
      control is based on a variable optical attenuator system that operates in
      synchronism with the photonic delay line (PDL). This amplitude control system can
      provide both the signal calibration for the different PDL channels and settings
      required for driving the antenna elements of a phased-array radar and the optimum
      optical power levels that impinge on the photodetector for optimum fiber-optic
      link performance. Various variable amplitude control modules based on
      ferroelectric liquid crystals, polymer-dispersed liquid crystals, and
      photoconductive devices are proposed. We show that the dynamic range loss due to
      a switched-PDL inherent structure loss can be compensated when we control the
      optical power from the laser, using the synchronous optical attenuation system.
      For the first time to our knowledge, full dynamic range loss compensation is
      demonstrated for an external-modulation-fed 3-bit switched PDL with a structure
      optical insertion loss of 5.5 dB. A compression dynamic range of 158 dBxHz was
      measured at 6 GHz, and a spurious free dynamic range of 111 dBxHz(2/3) was
      estimated. Feasibility of the dynamic range compensation technique for
      multichannel, higher-insertion-loss PDL systems is discussed.

PMID- 18319797
TI  - Determination of the complex index of refraction and size distribution of
      aerosols from polar nephelometer measurements.
AB  - The polar nephelometer of Tohoku University has been improved so that it can be
      used to measure the scattering matrix element D21. Polar nephelometer
      observations were conducted at Tohoku University in the suburbs of Sendai, Japan,
      from 12 October to 10 December 1988. A method presented in an earlier publication
      [Appl. Opt. 36, 7992 (1997)] is applied to determine the complex index of
      refraction and size distribution of aerosols simultaneously. It is shown that the
      accuracy of the determined quantities is reasonable.

PMID- 18319798
TI  - Influence of CO2-laser linewidth on the measured absorption coefficients of
      atmospheric water vapor and ammonia.
AB  - We describe the results of analysis of the experimental and calculated data on
      the water vapor and ammonia absorption coefficients of CO2-laser radiation. We
      believe that the different halfwidths of CO2-laser lines, caused by different
      pressures of the working mixtures in specific experiments, are probably the
      reason for discrepancies between data presented in various papers.

PMID- 18319799
TI  - Measurement of the spatial coherence of light influenced by turbulence.
AB  - To evaluate the Earth's surface with a sensor on a satellite, it is important for
      one to use a correction factor such as atmospheric turbulence. The spatial
      coherence of light influenced by turbulence was measured in the laboratory by use
      of a simulator equipped with a multiple reflection system. The turbulence was
      generated by changing the ambient temperatures from 32 to 48 degrees C. It was
      found that the spatial coherence of light that passed through the turbulent
      region decreased when the temperature increased. Double-slit interference fringes
      were analyzed by a photographic method. The visibility of the interference
      fringes is the degree of coherence.

PMID- 18319800
TI  - Microphysical particle parameters from extinction and backscatter lidar data by
      inversion with regularization: theory.
AB  - A method is proposed that permits one to retrieve physical parameters of
      tropospheric particle size distributions, e.g., effective radius, volume, surface
      area, and number concentrations, as well as the mean complex refractive index on
      a routine basis from backscatter and extinction coefficients at multiple
      wavelengths. The optical data in terms of vertical profiles are derived from
      multiple-wavelength lidar measurements at 355, 400, 532, 710, 800, and 1064 nm
      for backscatter data and 355 and 532 nm for extinction data. The algorithm is
      based on the concept of inversion with regularization. Regularization is
      performed by generalized cross-validation. This method does not require knowledge
      of the shape of the particle size distribution and can handle measurement errors
      of the order of 20%. It is shown that at least two extinction data are necessary
      to retrieve the particle parameters to an acceptable accuracy. Simulations with
      monomodal and bimodal logarithmic-normal size distributions show that it is
      possible to derive effective radius, volume, and surface-area concentrations to
      an accuracy of +/-50%, the real part of the complex refractive index to +/-0.05,
      and the imaginary part to +/-50%. Number concentrations may have errors larger
      than +/-50%.

PMID- 18319801
TI  - Microphysical particle parameters from extinction and backscatter lidar data by
      inversion with regularization: simulation.
AB  - A sensitivity study with an inversion scheme that permits one to retrieve
      physical parameters of tropospheric particle size distributions, e.g., effective
      radius, volume, surface-area, and number concentrations, as well as the mean
      complex refractive index from backscatter and extinction coefficients at multiple
      wavelengths is presented. The optical data for the analysis are derived from Mie
      scattering calculations for monomodal and bimodal logarithmic-normal
      distributions in the particle size range between 0.01 and 10 microm. The complex
      refractive index is taken between 1.33 and 1.8 in the real part and between 0 and
      0.1 in the imaginary part. The choice of these parameters takes account of
      properties of optically active atmospheric particles. The wavelengths were chosen
      at 355, 400, 532, 710, 800, and 1064 nm for the backscatter and at 355 and 532 nm
      for the extinction data, which are the available wavelengths of the two lidar
      systems at the Institute for Tropospheric Research. Cases of erroneous optical
      data of the order of as much as 20%, an unknown refractive index, which may also
      be wavelength and size dependent, as well as the a priori unknown modality of the
      particle size distribution were considered. It is shown that both extinction
      channels are necessary for determining the above-mentioned parameters within
      reasonable limits, i.e., effective radius, surface-area, and volume
      concentrations to an accuracy of +/-50%, the real part of the complex refractive
      index to +/-0.1, and the imaginary part to +/-50%. The number concentration may
      have errors larger than 50%. The overall performance of the inversion scheme
      permits the evaluation of experimental data on a routine basis.

PMID- 18319802
TI  - Atmospheric particulate absorption and black carbon measurement.
AB  - It is convenient to measure the optical attenuation A of the combination of a
      layer of atmospheric particulate matter and the quartz fiber filter on which it
      has been collected. The problem of relating A to the absorption and scattering
      coefficients k and s of the particulate matter itself is treated as a problem in
      diffuse reflectance spectroscopy using the KubelkaMunk theory. The results show
      that although, in general, A is a nonlinear function strongly dependent on both s
      and k, for a limited range of s and sample thickness d, A can be a practically
      linear function of k. Fortunately, this range includes that common to atmospheric
      particulate samples. Furthermore, it is shown that if the filter's reflectance is
      sufficiently high, A can be nearly independent of s. This is in agreement with
      experimental and, for the limiting case when the substrate filter reflectance is
      unity, theoretical results obtained by other researchers. Use of such
      measurements of A as a means of determining the black carbon mass loading C on a
      filter is also investigated. It is shown that when the black carbon mass fraction
      f(c) is high, as it is for samples collected in large urban areas, A is a
      predictable and practically linear function of C. However, when f(c) is low, as
      it is for many rural locations, then the slope of the function A(C) is strongly
      dependent on f(c), leading to possible overestimates of C. This problem can be
      alleviated by making the measurement of A at near-infrared wavelengths rather
      than in the visible spectrum.

PMID- 18319803
TI  - Spectral dependence of the scattering coefficient in case 1 and case 2 waters.
AB  - An approximate linear relationship between the scattering coefficient and the
      wavelength of light in the visible is found in case 1 and case 2 waters. From
      this relationship, we estimate scattering at an unknown wavelength from
      scattering at a single measured wavelength. This approximation is based on
      measurements in a 1.5-m-thick surface layer collected with an AC9 instrument at
      63 stations in the Arabian Sea, northern Gulf of Mexico, and coastal North
      Carolina. The light-scattering coefficient at 412 nm ranged from 0.2 to 15.1 m(
      1) in these waters, and the absorption coefficient at 412 nm ranged from 0.2 to
      4.0 m(-1). A separate data set for 100 stations from Oceanside, California, and
      Chesapeake Bay, Virginia, was used to validate the relationship. Although the
      Oceanside waters were considerably different from the developmental data set
      (based on absorption-to-scattering ratios and single-scattering albedos), the
      average error between modeled and measured scattering values was 6.0% for the
      entire test data set over all wavelengths (without regard to sign). The slope of
      the spectral scattering relationship decreases progressively from high
      scattering, turbid waters dominated by suspended sediments to lower-scattering,
      clear waters dominated by phytoplankton.

PMID- 18319804
TI  - Lidar equations for turbid media with pulse stretching.
AB  - Lidar equations for a system with multiple-scattering beam spreading and pulse
      stretching are developed from an analytical model for the beam spread function.
      The resulting lidar equations are transparent to the physics and with some simple
      approximations for system transfer functions become mathematically simple
      engineering models for system studies. Application to and comparison with a
      variety of lidar applications in ocean environments (turbidity and bathymetry)
      and clouds (aerosol scattering) are presented. These examples provide model
      validation. The lidar model developed represents a significant extension beyond
      historical lidar models that exclude pulse stretching. Their mathematical
      simplicity should foster use in a broader class of problems involving light
      propagation in turbid media.

PMID- 18319805
TI  - Derivation of temperature and pressure from submillimetric limb observations.
AB  - We demonstrate the feasibility of retrieval of temperature and pressure profiles
      from spaceborne limb-sounding spectroscopic measurements in the submillimetric
      region. Whether these profiles can be retrieved determines whether a
      submillimetric instrument can be self-sufficient as far as the atmospheric model
      is concerned or whether complementary sensors in other spectral regions,
      dedicated to temperature and pressure measurements, are needed. Molecular-oxygen
      transitions are selected for the purpose of temperature and pressure retrieval on
      the basis of realistic observational parameters. We use a mathematical model of
      the retrieval process to evaluate the information content of the spectral
      features and to study the trade-off between the uncertainty of the retrieved
      profiles and their vertical resolution. It is shown that, using only one oxygen
      transition and without any constraint, one can achieve uncertainties of 5% for
      both temperature and pressure from 10 to approximately 40 km of altitude with a
      vertical resolution of 3 km; above 40 km the vertical resolution needs to be
      degraded to limit the uncertainties. The possibility of exploiting a priori
      information is discussed, as well as the effects of external constraints that can
      be used to improve the quality of the retrieved profiles. The sources of
      systematic error that need to be considered for the compilation of the total
      error budget are also evaluated.

PMID- 18319806
TI  - Rayleigh-Mie Doppler wind lidar for atmospheric measurements. I. Instrumental
      setup, validation, and first climatological results.
AB  - Since 1989 Service d'Aeronomie du Centre National de la Recherche Scientifique
      has used an incoherent Doppler lidar technique for wind measurements in the
      atmosphere. A new-generation Rayleigh-Mie Doppler lidar has been designed and is
      currently operated at the Observatoire de Haute Provence (France). We give a
      detailed description of this instrument and highlight two important upgrades
      leading to quasi-simultaneous and absolute measurements of the wind from
      approximately 8 to 50 km altitude. The possible sources of error are identified
      and quantified in terms of accuracy in the wind determination. Experimental
      results are given in detail, and a validation of the measurements is performed
      with the help of ancillary data. A first climatological description of the mean
      wind is briefly reported.

PMID- 18319807
TI  - Rayleigh-Mie Doppler wind lidar for atmospheric measurements. II. Mie scattering
      effect, theory, and calibration.
AB  - A theoretical and experimental study is conducted for the direct-detection
      Doppler Lidar developed by the Service d'Aeronomie du Centre National de la
      Recherche Scientifique. Thanks to a specific design, the double-edge technique
      that applies primarily to Rayleigh scattering can also be employed in presence of
      aerosols backscatter. We focus on a careful estimate of the particle-induced
      error on the wind measurements. With a theoretical model for the Fabry-Perot
      interferometer and two sets of calibration measurements, the true spectral
      properties of the interferometer and the calibration curves are recovered.
      Furthermore, the particle-induced error is estimated for varying values of the
      scattering ratio at 532 nm. When applied to real atmospheric signals, this error
      is shown to be negligible. A comparison between ancillary data and the wind and
      backscatter ratio as retrieved from the Doppler lidar signals confirms our
      estimate.

PMID- 18319808
TI  - Comparison of spectral irradiance standards used to calibrate shortwave
      radiometers and spectroradiometers.
AB  - Absolute calibration of spectral shortwave radiometers is usually performed with
      National Institute of Standards and Technology (NIST) or NIST-traceable
      incandescent lamps. We compare 18 irradiance standards from NIST and three
      commercial vendors using the same spectrometer to assess their agreement with our
      working standard. The NIST procedure is followed for the 1000-W FEL lamps from
      NIST, Optronics, and EG&G. A modified calibration procedure developed by Li-Cor
      is followed for their 200-W tungsten-halogen lamps. Results are reproducible from
      one day to the next to approximately 0.1% using the same spectrometer.
      Measurements taken four months apart using two similar but different
      spectrometers were reproducible to 0.5%. The comparisons suggest that even NIST
      standards may disagree with each other beyond their stated accuracy. Some of the
      1000-W commercial lamps agreed with the NIST lamps to within their stated
      accuracy, but not all. Surprisingly, the lowest-cost lamps from Li-Cor agreed
      much better with the NIST lamps than their stated accuracy of 4%, typically
      within 2%. An analysis of errors leads us to conclude that we can transfer the
      calibration from a standard lamp to a secondary standard lamp with approximately
      1% added uncertainty. A field spectrometer was calibrated with a secondary
      standard, producing a responsivity for the spectrometer that was within 5% of the
      responsivity obtained by Langley calibration using routine field measurements.

PMID- 18319809
TI  - Extremely asymmetrical scattering of optical waves in nonuniform periodic Bragg
      arrays.
AB  - The extremely asymmetrical scattering (EAS) of bulk and guided electromagnetic
      waves in nonuniform periodic Bragg arrays with steplike variations of the grating
      amplitude is analyzed theoretically by means of a recently developed approach
      based on allowance for the diffractional divergence of the scattered wave. Arrays
      of finite and infinite widths are investigated. It is shown that, for thin
      nonuniform arrays, EAS has the same pattern as for uniform arrays with mean
      grating amplitude. On the contrary, for wide nonuniform arrays, the scattered
      wave amplitudes are well determined by local values of the grating amplitude. In
      this case, the energy of the scattered wave is shown to concentrate mainly in
      regions with smaller grating amplitude. The sensitivity of EAS to small
      imperfections of periodic arrays is investigated theoretically. The physical
      explanation of the observed effects is based on the diffractional divergence of
      the scattered wave.

PMID- 18319810
TI  - Linear control of the spectral characteristics of wavelength-selective components
      with a high-index tapered thin-film planar waveguide and a single-mode half
      coupler.
AB  - A simple system of linearly tunable fiber-film wavelength-dependent components is
      demonstrated that includes a linearly tapered high-index thin-film planar
      waveguide (PWG) evanescently coupled by a single-mode-fiber half-coupler. We
      present experimental and theoretical results for the linear tuning of spectral
      responses such as coupled power, resonance position (lambda0), and fiber output
      light polarization through position shifting of the linearly tapered PWG, in the
      direction of the propagating light in the fiber, over the half-coupler block. We
      achieved almost linear control of the spectral response by changing the
      temperature of mixture-of-oils and overlay-doped poly(methyl methacrylate) PWG's
      when the refractive index of the system decreases with temperature. The variation
      in thickness of the tapered film is along the direction of the interaction length
      of the system. Linear tapered PWG's that comprised a mixture of oils, BK7 glass,
      and overlay-doped PMMA with high refractive indices were fabricated that could
      operate the device at lower and higher modes. We investigated the dependence of
      tuning lambda0 on the PWG mode. Tuning by shifting of a linear tapered PWG over a
      fiber half-block is mode dependent, whereas tuning by changing the refractive
      index of a uniform PWG is mode independent. Wavelength shift Deltalambda0 is
      found to decrease with an increase in the resonant PWG mode number m for linearly
      tapered PWG's. A fiber-to-asymmetric linear tapered-PWG coupler, which maintains
      the taper slope to within a specific limit, can function as a linearly tunable
      polarizer for the light in the fiber.

PMID- 18319811
TI  - Aluminum-coated hollow glass fibers for ArF-excimer laser light fabricated by
      metallorganic chemical-vapor deposition.
AB  - A hollow fiber composed of a glass capillary tube and a metal thin film upon the
      inside of the tube is proposed for the delivery of ArF-excimer laser light. From
      theoretical analysis, aluminum is chosen as the metal layer. A thin aluminum film
      is deposited by metallorganic chemical-vapor deposition, with dimethylethylamine
      alane employed as the source material. Measured loss spectra in vacuum
      ultraviolet and ultraviolet regions and losses for ArF-excimer laser light show
      the low-loss property of the aluminum-coated fiber at the 193-nm wavelength of
      ArF-excimer laser light. The straight loss of the 1-m long, 1-mm-bore fiber is
      1.0 dB.

PMID- 18319812
TI  - Fiber-based 205-mW (27% efficiency) power-delivery system for an all-fiber
      network with optoelectronic sensor units.
AB  - An optical fiber power-delivery system has been developed. An analysis of the
      spectral response of every component in the system has been carried out.
      Experimental measurements of the system are presented. We obtained 205 mW of
      power (5.4 V, 38.3 mA), yielding 27.4% efficiency. As an application, a sensor
      module is optically powered. This is an electrically isolated system, inasmuch as
      it also sends the measured data through a fiber. Several other applications are
      envisaged in the fields of aerospace, avionics, and domotics.

PMID- 18319813
TI  - In-plane rotation analysis by two-wavelength electronic speckle interferometry.
AB  - A simple method is presented for the measurement of in-plane rotation (angle and
      sign) of an object by use of the conventional in-plane sensitive electronic
      speckle pattern interferometry technique combined with the two-wavelength laser
      diode method. The advantage of this method is that it can be used to measure the
      angle of rotation in a simple way by determination of fringe tilt. The
      experimental setup is described, and results are presented.

PMID- 18319814
TI  - Vibration: history and measurement with an extrinsic Fabry-Perot sensor with
      solid-state laser interferometry.
AB  - We have studied the history of vibration and demonstrate a laser-based noncontact
      interferometric vibration sensor. The sensor promises the measurement of
      microdisplacement by using a Fabry-Perot cavity formed between a partially coated
      gradient-index lens and a movable reflector. Displacement is determined by the
      detection of interference fringes caused by phase modulation within the cavity.
      The sensor was tested in conjunction with both multimode and single-mode fiber
      transmission. Calibration with multimode fiber produced a fringe-contrast
      function that decreased monotonically with displacement. This calibration allowed
      at least 30 fringes to be discriminated, giving a displacement resolution of
      0.034 microm across a range of 10.2 microm. Dynamic tests demonstrated a working
      range of at least 3.74 microm at frequencies as high as 2 kHz. Similar tests in
      which single-mode fiber was used indicated a dynamic working range of at least
      4.29 microm.

PMID- 18319815
TI  - Two-dimensional imaging of soot volume fraction in laminar diffusion flames.
AB  - A technique for acquiring two-dimensional soot-volume-fraction measurements in
      laminar flames has been demonstrated. The technique provides a map of very low
      noise concentration over a range of wavelengths (250-1100 nm). A noise level of
      0.0007 in extinction and a spatial resolution of 30-40 microm for soot
      concentration were achieved with an arc lamp source that was filtered to provide
      greater spatial coherence and a CCD detector. The broadband arc lamp source also
      allowed us to avoid the added noise resulting from speckle with coherent laser
      sources. Beam steering, due to refractive-index gradients in the flame, was
      measured and compared with theoretical predictions. The optical arrangement to
      minimize the effect of beam steering is described. As a result the beam steering
      had no effect on the soot measurements in the flames examined. Flame-transmission
      maps obtained with this system in an ethylene/air laminar diffusion flame are
      presented. Tomographic analysis from use of an Abel inversion of the line-of
      sight data to obtain radial profiles of soot concentration is described.

PMID- 18319816
TI  - Calibration of a computer-controlled precision wavemeter for use with pulsed
      lasers.
AB  - The design of a pulsed wavemeter to monitor the high-precision tuning of pulsed
      (as well as cw) laser sources is presented. This device is developed from a
      combination of silver-coated Fabry-Perot etalons with various plate spacings.
      These etalons provide stepwise refinement of the wavelength to be measured. The
      wavemeter is controlled by a computer through a CAMAC interface, which measures
      the absolute wavelength in the visible with an accuracy of 2 parts in 10(8). The
      time required for data acquisition and computation to measure the refined
      wavelength with a single 2-MHz CPU is less than 100 ms. We describe the
      calibration of the instrument over the wavelength range 400-850 nm. We obtain the
      required calibration lines by locking lasers on hyperfine transitions of iodine,
      uranium, rubidium, and cesium. Methods to reduce the number of calibration lines
      required for calibration of the system are described. The expected wavelength
      dependent phase shift of the silver coatings is compared with that measured for
      the etalon following calibration. The differences are larger than expected
      because of either optical aberations or the use of centroids to measure the
      fringe position.

PMID- 18319818
TI  - Switching of output coupling in a grating coupler by diffraction transition to
      the distributed Bragg reflector regime.
AB  - In a proposed switching grating coupler (SGC), the grating period Lambda is
      chosen so that the SGC converts from a first-order grating coupler to a third
      order distributed Bragg reflector by means of a small change in the guided mode
      index. The principle for switching the radiated wave power and the effective
      aperture of the SGC were experimentally confirmed by use of the thermo-optic
      effect of a polymer waveguide. The extinction of the peak intensity of the wave
      radiated by the SGC and collected by an external lens was measured to be 5 dB
      with a temperature change of 10 degrees.

PMID- 18319819
TI  - Thermal and optical properties of polymer hosts for solid-state dye lasers.
AB  - We present measurements of thermal and optical properties of poly(methyl
      methacrylate) (PMMA), PMMA modified by the addition of ethanol (MPMMA), and
      copolymers of methyl methacrylate with 2-hydroxyethyl methacrylate [P(HEMA:MMA)].
      Spectral transmission of the polymers is excellent (alpha = 0.5 cm(-1) at 400 nm,
      decreasing to 0.04 cm(-1) at 633 nm). Measured laser damage thresholds of MPMMA
      and P(HEMA:MMA) show at least a twofold increase over PMMA. Thermal lensing
      measured in these hosts doped with Rhodamine 6G is shown to be similar (f = -450
      mm for pump power of 200 mW in a 2-mm-diameter spot, scaling with pump
      intensity). Compared with MPMMA, P(HEMA:MMA) offers an improved surface quality
      and a more uniform dye distribution.

PMID- 18319820
TI  - Laser-induced bulk damage in various types of vitreous silica at 1064, 532, 355,
      and 266 nm: evidence of different damage mechanisms between 266-nm and longer
      wavelengths.
AB  - Laser-induced-damage thresholds (LIDT's) with various types of vitreous silica at
      1064, 532, 355, and 266 nm are investigated. At 1064 nm no difference in the LIDT
      was observed in any sample. At 1064-355 nm the wavelength dependence of the LIDT
      of synthetic fused silica (SFS) can be described well by the relation I(th) =
      1.45lambda(0.43), where I(th) is the LIDT in J/cm2 and lambda is the wavelength
      in nanometers. At 266 nm, however, LIDT's were smaller than half of the
      calculated value from the relation above. This difference can be explained by the
      damage mechanism; at 266 nm two-photon absorption-induced defects lower the LIDT
      as in the case of KrF-excimer-laser-induced defects, whereas at longer
      wavelengths the two-photon process does not occur. LIDT's of fused quartz (FQ) at
      532 and 355 nm and that of SFS containing approximately 1000 ppm of Cl and no OH
      at 355 nm were a little lower than those of the other SFS's. This lower LIDT may
      be related to the absorption of metallic impurities in FQ and dissolved Cl2
      molecules in SFS. At 266 nm, on the other hand, LIDT's of FQ's were higher than
      those of most SFS's.

PMID- 18319821
TI  - Design and operation of a very large ring laser gyroscope.
AB  - The design and initial operation of a vertical square He-Ne ring laser G0 with a
      perimeter of 14 m is discussed. This builds on earlier demonstrations of the
      feasibility of large ring lasers (perimeter approximately 4 m) for single-mode
      gyroscope operation and with lesser pulling than navigation gyroscopes. With
      servoing of the rf excitation to yield single-mode operation, G0 gave a quality
      factor 1 x 10(12) and a Sagnac line with a frequency of 287.8 +/- 1.0 Hz induced
      by Earth rotation Omega(E). This has confirmed some vital questions over the
      feasibility of very large gyroscopes for geodetic measurements at the level of
      10(-9) Omega(E).

PMID- 18319822
TI  - Theoretical treatment of fluorescence detection by a dual-fiber-optic sensor with
      consideration of sampling variability and package effects associated with
      particles.
AB  - The characteristics of a dual-fiber-optic sensor for measurements of chlorophyll
      fluorescence in aquatic environments were evaluated with a theoretical model.
      Consideration was given to sampling variability and package effects associated
      with particles (e.g., phytoplankton cells). A numerical simulation was developed
      to approximate the optical geometry of the dual fiber-optic sensor that permitted
      a visual representation of the fluorescence distribution within the sensor
      sampling volume. A Monte Carlo simulation was used to evaluate sampling
      variability associated with the number and distribution of particles within the
      sampling volume. Relatively high coefficients of variation were associated with
      low particle concentrations, although with sufficient signal averaging the
      coefficient of variation was reduced to less than 20%. The influence of package
      effects and intracellular absorption of fluorescence was evaluated with a
      simplified form of the model that treated fluorescence as a linear function of
      particle density and assumed uniform particle composition, constant fluorescence
      cross-sectional yield, and sufficient averaging of the fluorescence signal. The
      model predicted decreasing fluorescence per unit of chlorophyll with increasing
      values of the product of particle diameter and intraparticle chlorophyll
      concentration. Experimental trends in size dependence of chlorophyll-fluorescence
      relationships were compared with predictions of the model.

PMID- 18319823
TI  - Intracavity testing of KTiOPO4 crystals for second-harmonic generation at 532 nm.
AB  - We have developed a diode-pumped Nd:YVO4 cw laser for testing KTiOPO4 crystals
      designed for intracavity second-harmonic generation at 532 nm. We demonstrate
      that this source is extremely sensitive to defects inside the crystal, inducing
      losses at 1064 nm and an index mismatch between fundamental and harmonic waves.

PMID- 18319824
TI  - Deceleration of a calcium atomic beam with a frequency-doubled diode laser.
AB  - A calcium atomic beam has been decelerated by a single extended-cavity diode
      laser, frequency doubled to 423 nm. A potassium niobate crystal is placed in an
      external power buildup cavity, and the second-harmonic laser beam,
      counterpropagating with the atomic beam, is tuned into resonance with the strong
      1S0-1P1 transition of calcium. For input power of 78 mW at 846 nm, we generate 22
      mW at 423 nm after correction for the reflectivity of our cavity output coupler.
      To keep the atoms always in resonance during the deceleration process, the Zeeman
      tuning technique was used.

PMID- 18319825
TI  - High-speed random access laser tuning.
AB  - We have developed a technique for laser tuning at rates of 100 kHz or more using
      a pair of acousto-optic modulators. In addition to all-electronic wavelength
      control, the same modulators also can provide electronically variable Q
      switching, cavity length and power stabilization, chirp and linewidth control,
      and variable output coupling, all at rates far beyond what is possible with
      conventional mechanically tuned components. Tuning rates of 70 kHz have been
      demonstrated on a radio-frequency-pumped CO2 laser, with random access to over 50
      laser lines spanning a 17% range in wavelength and with wavelength discrimination
      better than 1 part in 1000. A compact tuner and Q-switch has been deployed in a 5
      10-kHz pulsed lidar system. The modulators each operate at a fixed Bragg angle,
      with the acoustic frequency determining the selected wavelength. This arrangement
      doubles the wavelength resolution without introducing an undesirable frequency
      shift.

PMID- 18319826
TI  - Passively Q-switched 1.57-microm intracavity optical parametric oscillator.
AB  - We demonstrate an eye-safe KTP-based optical parametric oscillator (OPO) driven
      intracavity by a diode-pumped 1064-nm Nd:YAG laser, passively Q-switched by a
      Cr4+:YAG crystal. The characteristics of this system, which operates at 1570 nm
      with a repetition rate as high as 50 Hz, are studied as a function of Cr4+:YAG
      optical density. Under optimum conditions the OPO generates 1.5-mJ, 3.4 +/- 0.1
      ns pulses in a single transverse mode. For a Cr4+:YAG Q-switch element with an
      optical density of 0.5 the conversion efficiency of the intracavity energy is
      approximately 45% with the ratio of OPO to Nd:YAG peak-pulse intensity exceeding
      unity. These and other OPO characteristics compare favorably with a simple rate
      equation model of the OPO dynamics.

PMID- 18319827
TI  - Generation of 6.6-microm optical parametric oscillation with periodically poled
      LiNbO3.
AB  - Greater than 6-microm-oscillation was demonstrated by means of optical parametric
      oscillation with periodically poled LiNbO3 (PPLN). The interaction length and
      thickness were 40 mm and 500 microm. The pump source used was a Q-switched Nd:YAG
      laser with a pulse duration of 120 ns and a repetition rate of 1 kHz. The tuning
      ranges of the idler waves were 6.57-6.56, 6.22-6.12, and 6.06-5.94 microm for
      PPLN wafers of 20-, 21.3-, and 22-microm periods, respectively.

PMID- 18319828
TI  - Optical characteristics of stretched silver island multilayers for submicrometer
      thick optical polarizing films.
AB  - We fabricated submicrometer-thick optical polarizing films at a wavelength of
      1300 nm with extinction ratios of > or = 30 dB by stretching periodic multilayers
      of silver island layers and glass layers. We compared the measured and
      theoretical optical characteristics of the polarizing films. The measured optical
      characteristics were quantitatively different from preliminary theoretical ones
      reported in an earlier paper [Opt. Lett. 16, 964 (1991)]. We have improved the
      theory by considering the distribution in silver island shapes and the difference
      between the stretching ratios of the glass layers and the silver islands. We have
      successfully elucidated the optical characteristics of the fabricated optical
      polarizing films.

PMID- 18319829
TI  - Liquid-crystal luminaire consisting of an optical shutter and a metal halide
      lamp.
AB  - We made a liquid-crystal (LC) luminaire for the first time to our knowledge by
      combining a metal halide lamp and an optical shutter composed of a compound of a
      very high nematic-isotropic point (172 degrees C) LC and a polymer (CLCP). The
      shutter can modulate high-power light independently of the state of polarization
      because the CLCP film becomes transparent or opalescent when either sufficiently
      high or no voltage is applied to it. To solve the problem, which is peculiar to
      CLCP films, that the color temperature of light modulated by the film changes
      with the film's transmittance, a pulse-width modulation method that varies the
      time ratio of the on and off states of the shutter was developed. The performance
      characteristics of the luminaire were as follows: illuminance range, 192 to
      10,400 lx at a distance of 5 m from the luminaire; rise and decay times, 1.4 and
      1.5 ms; color temperature, 4060-5600 K; operation room temperature, approximately
      150 degrees C; stable operation time, more than 2000 h. Experimental results show
      the feasibility of applications of this luminaire in various fields, including
      television, movie, and stage lighting.

PMID- 18319830
TI  - Using the spectral asymmetry of TEA CO2 laser pulses to determine the Doppler
      shift sign in coherent lidars with low frequency stability.
AB  - We develop a method for determinating the relative positions of the lidar
      transmitter (LT) and the local oscillator (LO) frequencies in Doppler CO2 lidars.
      It uses the weak spectral asymmetry of TEA CO2 laser pulses, defined by a number
      of secondary peaks at the high-frequency side of the main spectrum peak.
      Depending on the sign of the beat frequency, these peaks may appear in the
      demodulated spectrum at either the high- or the low-frequency side. Each laser
      pulse spectrum is compared with reference spectra with two types of asymmetry,
      with the cross-correlation coefficients used as criteria. The performance of the
      method at different values of signal-to-noise ratio is analyzed numerically. The
      method is also applied to raw data from the lidar reference channel and
      demonstrates good performance at noise levels lower than the secondary peaks in
      the pulse spectrum or at a signal-to-noise ratio of > or = 20 dB. Application of
      the pulse spectrum asymmetry for lidar frequency stabilization is analyzed. Lidar
      operation without frequency stabilization is considered as well. The method
      offers a simple Doppler lidar hardware for the creation of low-cost coherent
      lidars, velocimeters-rangefinders, etc.

PMID- 18319831
TI  - Laser remote-sensing system analysis for search and rescue.
AB  - We develop a general model of a laser remote-sensing system for search and rescue
      using targets marked with fluorescent dye. The dye fluoresces at a longer peak
      wavelength than the incident radiation, enabling a dye-covered target to be
      distinguished from the unshifted ground echo by the search system. The principal
      result is a simple expression derived for the average laser power required to
      search at a particular rate given a required ground energy density. A similar
      expression is applicable to imaging lidar systems. The example system shown
      indicates that active probing for lost planes may be practical.

PMID- 18319832
TI  - Tunable Fabry-Perot etalon-based long-wavelength infrared imaging
      spectroradiometer.
AB  - Imaging spectrometry enables passive, stand-off detection and analysis of the
      chemical composition of gas plumes and surfaces over wide geographic areas. We
      describe the use of a long-wavelength infrared imaging spectroradiometer,
      comprised of a low-order tunable Fabry-Perot etalon coupled to a HgCdTe detector
      array, to perform multispectral detection of chemical vapor plumes. The tunable
      Fabry-Perot etalon used in this research provides coverage of the 9.5-14-microm
      spectral region with a resolution of 7-9 cm(-1). The etalon-based imaging system
      provides the opportunity to image a scene at only those wavelengths needed for
      chemical species identification and quantification and thereby minimize the data
      volume necessary for selective species detection. We present initial results
      using a brassboard imaging system for stand-off detection and quantification of
      chemical vapor plumes against near-ambient-temperature backgrounds. These data
      show detection limits of 22 parts per million by volume times meter (ppmv x m)
      and 0.6 ppmv x m for dimethyl methyphosphonate and SF6, respectively, for a
      gas/background DeltaT of 6 K. The system noise-equivalent spectral radiance is
      approximately 2 microW cm(-2) sr(-1) microm(-1). Model calculations are presented
      comparing the measured sensitivity of the sensor to the anticipated signal levels
      for two chemical release scenarios.

PMID- 18319833
TI  - Rocketborne Rayleigh lidar for in situ measurements of neutral atmospheric
      density.
AB  - We describe the design of a small Rayleigh scattering lidar for launch on a
      sounding rocket as well as the first, to our knowledge, in situ measurements of
      neutral number density performed with a rocketborne lidar in the mesosphere. The
      aim of the experiment is to study the dynamics of the neutral atmosphere with
      emphasis on turbulent structures and gravity waves. The altitude resolution of
      the density profile is better than 10 m. The uncertainty is 0.3% below 55 km and
      better than 1% to an altitude of 65 km. The lidar technique meets the requirement
      of measurement of total molecular density outside the shock front surrounding the
      supersonic payload, which is necessary for precision measurements of neutral
      atmospheric density. We have compared different component technologies and design
      approaches and show performance calculations for two electro-optical systems. The
      first system has laser and detector components that were available in 1993, the
      second has new solutions that became available in 1995. The second system has a
      signal-to-noise ratio that is five times higher than the first and employs a
      pulsed high-power laser diode array as the transmitter and a large-area avalanche
      photodiode as the receiver.

PMID- 18319834
TI  - Measurement of an isosbestic point in the Raman spectrum of liquid water by use
      of a backscattering geometry.
AB  - Measurements presented here confirm that a temperature-insensitive point occurs
      in the backscattered Raman spectrum from liquid water. This result, coupled with
      existing laboratory measurements of Raman scattering from liquid droplets,
      indicates that a Raman lidar measurement of cloud liquid water is feasible.

PMID- 18319835
TI  - Backscattering measurements of atmospheric aerosols at CO2 laser wavelengths:
      implications of aerosol spectral structure on differential-absorption lidar
      retrievals of molecular species.
AB  - The volume backscattering coefficients of atmospheric aerosol were measured with
      a tunable CO2 lidar system at various wavelengths in Utah (a desert environment)
      along a horizontal path a few meters above the ground. In deducing the aerosol
      backscattering, a deconvolution (to remove the smearing effect of the long CO2
      lidar pulse and the lidar limited bandwidth) and a constrained-slope method were
      employed. The spectral shape beta(lambda) was similar for all the 13 measurements
      during a 3-day period. A mean aerosol backscattering-wavelength dependence
      beta(lambda) was computed from the measurements and used to estimate the error
      Delta(CL) (concentration-path-length product) in differential-absorption lidar
      measurements for various gases caused by the systematic aerosol differential
      backscattering and the error that is due to fluctuations in the aerosol
      backscattering. The water-vapor concentration-path-length product CL and the
      average concentration C = <CL>/L for a path length L computed from the range
      resolved lidar measurements is consistently in good agreement with the water
      vapor concentration measured by a meteorological station. However, I was unable
      to deduce, reliably, the range-resolved water-vapor concentration C(r), which is
      the derivative of the range-dependent product CL, because of the effect of
      residual noise caused mainly by errors in the deconvolved lidar measurements.

PMID- 18319836
TI  - External photoacoustic detection of a trace vapor inside a multimode laser.
AB  - We combine highly sensitive intracavity absorption spectroscopy in a multimode
      laser with external photoacoustic detection, providing high detectivity.
      Photoacoustic measurements of the intracavity iodine concentration in a Rhodamine
      6G laser are compared with simultaneous spectral recordings. They demonstrate
      slightly improved overall sensitivity and a greatly enhanced dynamic range of 5
      orders of magnitude that may be shifted along the absolute scale of absorber
      density.

PMID- 18319837
TI  - Development of Fourier transform spectrometry for UV-visible differential optical
      absorption spectroscopy measurements of tropospheric minor constituents.
AB  - Concentration measurements of trace gases in the atmosphere require the use of
      highly sensitive and precise techniques. The UV-visible differential optical
      absorption spectroscopy technique is one that is heavily used for tropospheric
      measurements. To assess the advantages and drawbacks of using a Fourier transform
      spectrometer, we built a differential optical absorption spectroscopy optical
      setup based on a Bruker IFS 120M spectrometer. The characteristics and the
      capabilities of this setup have been studied and compared with those of the more
      conventional grating-based instruments. Two of the main advantages of the Fourier
      transform spectrometer are (1) the existence of a reproducible and precise wave
      number scale, which greatly simplifies the algorithms used to analyze the
      atmospheric spectra, and (2) the possibility of recording large spectral regions
      at relatively high resolution, enabling the simultaneous detection of numerous
      chemical species with better discriminating properties. The main drawback, on the
      other hand, is due to the fact that a Fourier transform spectrometer is a
      scanning device for which the scanning time is small compared with the total
      measurement time. It does not have the signal integration capabilities of the CCD
      or photodiode array-based grating spectrographs. The Fourier transform
      spectrometer therefore needs fairly large amounts of light and is limited to
      short to medium absorption path lengths when working in the UV.

PMID- 18319838
TI  - Passage of light through a dispersion medium with a high concentration of
      discrete inhomogeneities: experiment.
AB  - The passage of light through dispersion layers consisting of large weakly
      absorbing scatterers has been investigated. Measurements of the transmittance and
      the angular structure of scattered radiation have been made. The dependence of
      these characteristics on the thickness and the concentration of scatterers has
      been analyzed.

PMID- 18319839
TI  - Cylindrical localized approximation to speed up computations for Gaussian beams
      in the generalized Lorenz-Mie theory for cylinders, with arbitrary location and
      orientation of the scatterer.
AB  - A cylindrical localized approximation to speed up numerical computations in
      generalized Lorenz-Mie theory for cylinders, in a special case of perpendicular
      illumination, was recently introduced and rigorously justified. We generalize
      this approximation to the case when the cylinder is arbitrarily located and
      arbitrarily oriented in a Gaussian beam.

PMID- 18319840
TI  - Elastic laser light scattering by GaAs surfaces.
AB  - Angle-resolved scattering (ARS) intensities were measured in the backscattering
      hemisphere for the (1 0 0) and (1 1 1) faces of GaAs single crystals. Three
      epitaxial layers were deposited onto the GaAs (1 0 0) single-crystalline wafers.
      The laser elastic light scattering shows the presence of a regular surface
      microrelief whose orientation corresponds to the crystallographic axes in the
      surface plane. We studied the statistical properties of this microrelief and
      determined the parameters that characterize the surface. We propose to use the
      ARS ratio for two wavelengths (in our case, 632.8 and 441.6 nm) to determine the
      topographical properties of scattering and to study crystal surface defects.

PMID- 18319841
TI  - Inversion of particle-size distribution from angular light-scattering data with
      genetic algorithms.
AB  - A stochastic inverse technique based on a genetic algorithm (GA) to invert
      particle-size distribution from angular light-scattering data is developed. This
      inverse technique is independent of any given a priori information of particle
      size distribution. Numerical tests show that this technique can be successfully
      applied to inverse problems with high stability in the presence of random noise
      and low susceptibility to the shape of distributions. It has also been shown that
      the GA-based inverse technique is more efficient in use of computing time than
      the inverse Monte Carlo method recently developed by Ligon et al. [Appl. Opt. 35,
      4297 (1996)].

PMID- 18319842
TI  - In situ light-scattering measurements of morphologically evolving flame
      synthesized oxide nanoaggregates.
AB  - Nonspherical Al2O3 aggregates produced in a laminar counterflow nonpremixed
      methane flame were investigated with an in situ laser light-scattering (LLS)
      technique in combination with a thermophoretic sampling-transmission electron
      microscope (TS-TEM) method. These flame-synthesized nanoparticles clearly
      underwent morphological changes following their formation (from precursor
      trimethylaluminum hydrolysis), mainly as a result of aggregation and sintering
      processes in the approximately 3.3 x 10(4) K/s heating environment. To
      characterize this particulate morphological evolution conveniently we made
      multiangular absolute LLS measurements and interpreted them based on the Rayleigh
      Debye-Gans scattering theory for fractal aggregates. Optically determined fractal
      dimension D(f), mean radius of gyration, aggregate size distribution, and local
      particle volume fraction phi(p) were found to be consistent with our independent
      ex situ TS-TEM experiments. D(f) (optically inferred) increased from 1.60 to 1.84
      with axial position, confirming the morphological evolution of alumina aggregates
      owing to finite-rate, spatially resolved high-temperature sintering. An extension
      of our TS-TEM method was successfully applied, for the first time to our
      knowledge, to inorganic particles. Phi(p) inferred by means of this ex situ
      technique generally agreed with that from the in situ LLS technique, supporting
      our interpretation of both measurements. Moreover, an optically inferred net
      sintering rate of alumina aggregates approaching the flame was estimated to be
      consistent with the available TEM data. The LLS methods and results presented
      here are expected to permit more comprehensive mechanistic analyses of
      nanoaggregate sintering and coagulation kinetics in such flame environments,
      ultimately improving the modeling of more-complex (e.g., turbulent, high
      pressure) combustion systems involving nanoparticle formation and evolution.

PMID- 18319843
TI  - Optical particle-sizing method that provides optical isolation of the sampling
      volume.
AB  - We have constructed and tested a novel particle sizer that employs particle
      counting (the time-domain approach) rather than the ensemble-diffraction approach
      that currently dominates the market in atmospheric-dust particle sizers. The
      method does not depend on mechanical devices to restrict particles within the
      sampling volume but instead allows for optical isolation of the sampling volume.
      This technique is useful for atmospheric-dust measurements for which nonobtrusive
      measurement is often desirable.

PMID- 18319844
TI  - Filling in of Fraunhofer and gas-absorption lines in sky spectra as caused by
      rotational Raman scattering.
AB  - A line-by-line radiative-transfer model to quantify the Ring effect as caused by
      rotational Raman scattering has been developed for the 310-550-nm spectral
      interval. The solar zenith angle and the resolution are key input parameters, as
      is the sky spectrum (excluding inelastic atmospheric scattering), which was
      modeled with MODTRAN 3.5. The filling in is modeled for ground-based viewing
      geometry and includes surface reflection and single inelastic scattering. It is
      shown that O2 contributes half of the filling in of N2. A strong inverse
      relationship with wavelength is noted in the filling in. A comparison with
      observations shows moderate agreement. The largest filling in occurs in the Ca II
      K and H lines.

PMID- 18319845
TI  - Upconversion and reduced 4F(3/2) upper-state lifetime in intensely pumped Nd:YLF.
AB  - Nonexponential decay of the 4F(3/2) upper laser state in Nd:YLF was observed with
      time-resolved fluorescence spectroscopy and small-signal gain probes in low-doped
      (1.16-at. %) samples when intensely pumped to high population inversions. A rapid
      initial decay is observed after Q-switched laser pumping, followed by a longer
      nonexponential decay that is clearly identified as a phase of migration-assisted
      energy-transfer upconversion (ETU) in the hopping regime. During this phase, a
      rate-equation treatment is valid and the macroscopic ETU coefficient, alpha2 =
      (0.98 +/- 0.03) x 10(-16) cm3/s, is directly evaluated from the decay kinetics.
      The ETU and the migration microparameters are also estimated to be C(da)*
      approximately 200 x 10(-40) cm6/s and C(dd) approximately 1000 x 10(-40) cm6/s,
      respectively, and are compared with theoretical values found in the literature.
      On the basis of these values, rate-equation treatments of intensely pumped Nd:YLF
      are not strictly valid.

PMID- 18319846
TI  - Nondestructive inspection of Phaseolus coccineus L. soya beans by use of near
      infrared lasers.
AB  - We propose a nondestructive inspection method for the quantitative analysis of
      molds inside soya beans (Phaseolus coccineus L.) that does not render the beans
      unfit for human consumption. Three near-infrared lasers are used for
      multispectral transmission imaging of the beans. Eigenvalue analysis and a least
      squares method are used for estimation of the diffuse reflectance spectrum of
      each type of mold. The estimated spectra are used for determining the internal
      concentration of the molds inside the beans. Experimental results verify the
      usefulness of our method.

PMID- 18319847
TI  - Method of phase-Doppler anemometry free from the measurement-volume effect.
AB  - A novel method is developed to improve the accuracy of particle sizing in laser
      phase-Doppler anemometry (PDA). In this method the vector sum of refractive and
      reflective rays is taken into consideration in describing a dual-mechanism
      scattering model caused by a nonuniformly illuminated PDA measurement volume. The
      constraint of the single-mechanism-scattering model in the conventional PDA is
      removed. As a result the error caused by the measurement-volume effect, which
      consists of a Gaussian-beam defect and a slit effect, can be eliminated. This new
      method can be easily implemented with minimal modification of the conventional
      PDA system. The results of simulation based on the generalized Lorenz-Mie theory
      show that the new method can provide a PDA system free from the measurement
      volume effect.

PMID- 18319848
TI  - Optimum design of a grazing-incidence flat-field spectrograph with a spherical
      varied-line-space grating.
AB  - A grazing-incidence spectrograph is designed by use of the flat-field image
      focusing property of a spherical varied-line-space grating. Optimum grating
      parameters for mechanical ruling are selected by application of genetic
      algorithms. Two gratings, one for 2-5-nm and the other for 5-20-nm spectral
      regions, are designed, and their fabrication tolerances are analyzed.

PMID- 18319849
TI  - Simultaneous measurement of strain and temperature by use of a single-fiber Bragg
      grating and an erbium-doped fiber amplifier.
AB  - We propose and demonstrate a novel sensor by using a single-fiber Bragg grating
      that can simultaneously measure strain and temperature with the aid of an erbium
      doped fiber amplifier. By using a linear variation in the amplified spontaneous
      emission power of the erbium-doped fiber amplifier with temperature, we determine
      the temperature. By subtracting the temperature effect from the fiber Bragg
      grating Bragg wavelength shift, we determine the strain. Experiments show rms
      deviations of 18.2 microepsilon and 0.7 degrees C for strain and temperature,
      respectively.

PMID- 18319850
TI  - Fiber Bragg grating temperature sensor with controllable sensitivity.
AB  - We demonstrate a fiber Bragg grating (FBG) sensor with controllable sensitivity
      by connecting two metal strips that have different temperature-expansion
      coefficients. By changing the lengths of the metal strips we successfully
      controlled and improved the temperature sensitivity to 3.3 times of that of bare
      FBG.

PMID- 18319851
TI  - Structural monitoring by use of a Brillouin distributed sensor.
AB  - The testing of a fiber-optic distributed-strain sensor attached to a simple
      structural member is reported. A Brillouin scattering-based sensor system was
      used to measure both tensile and compressive strains along the length of a
      cantilever beam subjected to various loads. The sensing fiber was attached to the
      beam in such a way that some sections experienced uniform strain, whereas others
      were subjected to a nonuniform strain distribution. A spatial resolution of 0.4 m
      was used, and a measurement precision of approximately +/-50 microepsilon was
      achieved.

PMID- 18319852
TI  - Modified in-line Sagnac interferometer with passive demodulation technique for
      environmental immunity of a fiber-optic current sensor.
AB  - A modified in-line Sagnac interferometer (MISI) with passive demodulation
      Technique (PDT) was proposed to immunize the fiber-optic current sensor (FOCS)
      from environmental perturbations. A large vibration to simulate the environmental
      perturbations with acceleration up to 12 g was applied to the lead fiber of the
      FOCS. The noise floor could be significantly suppressed (20 dB) by the MISI
      better than by a conventional interferometer. In the same dynamic environments,
      the PDT could make the FOCS achieve a good linear demodulation with average
      distortion rates always lower than 0.9%. In addition, all the sensitivities
      measured in both static and dynamic environments are all approximately 4.5
      microrad/(A(rms) turns), which is close to the literatural data measured in
      static environments. These considerable achievements of high sensitivity,
      environmental immunity, and free electric shock concerns may lead FOCS's to field
      monitoring applications of power delivery lines.

PMID- 18319853
TI  - Proof-testing and probabilistic lifetime estimation of glass fibers for sensor
      applications.
AB  - The mechanical reliability of sensing glass fiber is one of the important
      problems in the practical use of fiber-optic sensors. To ensure long-term
      reliability on a mass-production level, a method of proof-testing is applied to a
      sensing glass fiber that will be subjected to mechanical deformation in its
      service situation. We propose to employ a higher strain level (screening level)
      in the proof-testing with a fiber-recoating technique that can suppress excessive
      damage during the testing. We consider a standard lifetime of 15 years of
      automotive applications and ensure a practical level of failure probability by a
      model calculation by using the strength data of a prototype fiber with the method
      of fracture-mechanics theory.

PMID- 18319854
TI  - Viewing angle of liquid-crystal displays: representation on the Poincare sphere.
AB  - Using the extended Jones calculus for oblique incidence, we have succeeded in
      representing light propagation through birefringent media on the Poincare sphere
      for arbitrary propagation directions. The situation is far more complicated than
      for the case of perpendicular transmission. To achieve a simple representation
      method we had to define appropriate conventions. One can use the method to
      evaluate the efficiency of existing viewing-angle compensation foils. The
      Poincare sphere turns out to be a valid geometrical method for the design of new
      compensation foils that optimize the contrast ratio. The different parameters of
      a homogeneous compensation foil that is applied to a liquid-crystal display to
      improve the viewing-angle properties can be systematically determined.

PMID- 18319855
TI  - Transmittance of skew rays through metal light pipes.
AB  - The transmittance of skew rays through metal light pipes is examined with ray
      tracing. The transmittance with respect to pipe length is compared with
      analytical approximations and with experimental data. The effects of pipe
      material, pipe shape, wavelength of the incident light, distribution of the
      incident light, and maximum angle of incidence on transmittance are examined. The
      transmittance is shown, in general, not to be exponential with respect to pipe
      length. Additionally, the effect on transmittance of elbows and gaps in a pipe is
      investigated.

PMID- 18319856
TI  - Super high resolution for long-range imaging.
AB  - A new optical system with a resolution that is superior to the resolution of the
      usual optical systems with diffraction limit is presented. We introduce a newly
      generated narrow light beam that propagates for a long range while almost
      maintaining its beam width and show that the beam width is narrower than that of
      the diffraction limit of normal optics. Thus a super high resolution is achieved
      for a long range, e.g., a range of a few kilometers, by the use of a 10-cm
      diameter telescope. The high resolution for long-range imaging can be obtained by
      a Galilean telescope with a negative eyepiece that has a spherical aberration. We
      demonstrate theoretically high-resolution imaging by using simple objects and
      assuming a telescope 10 cm in diameter and a visible wavelength. A comparison of
      simulation results by the conventional optical system and by the special optical
      system clearly shows the superiority of the new system.

PMID- 18319857
TI  - Techniques for measuring aberrations in lenses used in photolithography with
      printed patterns.
AB  - In optical lithography, it is a serious problem that aberrations in projection
      lenses reduce the imaging quality. Therefore techniques to measure the
      aberrations are required that will predict the adverse effects of aberrations on
      lithographic imagery and reduce them. We present a measurement method that uses a
      fine grating and its imaging condition to quantify coma, astigmatism, and
      spherical aberration. With this method, these aberrations can be described with
      simple expressions from the measured results. Application of this method revealed
      the coma of Zernike polynomials for our krypton fluoride (KrF) excimer-laser
      scanner.

PMID- 18319858
TI  - Current sensor using heterodyne detection.
AB  - Based on the Faraday effect for measuring ac current, we describe a fiber-optic
      sensor that uses laser-diode intensity modulation to perform heterodyne signal
      detection. The sensor output at the carrier frequency is used as a reference
      signal to normalize the results. The sensing element consists of a few coils low
      birefringence fibers between polarizers. We built the current sensor described
      above and tested its performance--sensitivity and noise--as functions of the
      angle between polarizers.

PMID- 18319859
TI  - Measurement of ultrasonic pressure by heterodyne interferometry with a fiber-tip
      sensor.
AB  - A fiber-optic measurement system is described that allows ultrasound to be
      detected in fluids. It is based on a heterodyne interferometer, and the sensing
      element consists of a metal-coated fiber tip. The heterodyne technique permits
      direct acquisition of the sound pressure. The required ac photodetection is
      carried out with wide bandwidth, and the system provides high temporal and
      spatial resolution. For optimum performance the system parameters are matched to
      the sound-wave properties of the current application with the aid of theoretical
      and numerical calculations. The fiber-optic sensor system was applied to two
      problems of ultrasonic exposimetry in which the favorable features of the
      measurement technique were exploited. Shock waves from an electromagnetic
      lithotripter were investigated by use of the wide bandwidth of the system, and
      the subharmonic in an ultrasonic cleaner was detected, which indicates
      cavitation.

PMID- 18319860
TI  - Comparison of temperature resolution of single-band, dual-band, and multiband
      infrared systems.
AB  - A new measure of temperature resolution of IR systems called noise-generated
      error (NGE) was recently proposed. The NGE does not have limitations of the
      classical noise-equivalent temperature difference and can be used to describe the
      resolution of single-band, dual-band, and multiband IR measurement systems. The
      results of theoretical and experimental testing of the temperature resolution NGE
      of a developed model of single-band, dual-band, and multiband pyrometers are
      presented.

PMID- 18319861
TI  - Profile measurement taken with liquid-crystal gratings.
AB  - Profile measurement taken with liquid-crystal gratings and a phase-shifting
      technique is proposed, and its effectiveness is verified by experiment. The
      surface profile is obtained by measurement of the phase distributions of the
      sinusoidal gratings deformed by an object's surface. The liquid-crystal grating
      gives an accurate phase shift, an arbitrary projection pitch, and a constant
      surface brightness compared with conventional gratings such as a laser
      interference fringe grating and a Ronchi grating. Therefore a flexible measuring
      system may be developed with it. Two gratings with different pitches are used to
      measure an object with large steps. A two-color projection system can be used to
      produce such gratings simultaneously. Locally varying reflectivity on a surface
      can also be compensated by adjustment of the color component of the projected
      grating with a liquid-crystal grating. Thus the contrast in the projected grating
      can be made uniform, and a good profile measurement can be accomplished.

PMID- 18319862
TI  - Performance optimization and light-beam-deviation analysis of the parallel-slab
      division-of-amplitude photopolarimeter.
AB  - A division-of-amplitude photopolarimeter that uses a parallel-slab multiple
      reflection beam splitter was described recently [Opt. Lett. 21, 1709 (1996)]. We
      provide a general analysis and an optimization of a specific design that uses a
      fused-silica slab that is uniformly coated with a transparent thin film of ZnS on
      the front surface and with an opaque Ag or Au reflecting layer on the back.
      Multiple internal reflections within the slab give rise to a set of parallel,
      equispaced, reflected beams numbered 0, 1, 2, and 3 that are intercepted by
      photodetectors D(0), D(1), D(2), and D(3), respectively, to produce output
      electrical signals i(0), i(1), i(2), and i(3), respectively. The instrument
      matrix A, which relates the output-signal vector I to the input Stokes vector S
      by I = AS, and its determinant D are analyzed. The instrument matrix A is
      nonsingular; hence all four Stokes parameters can be measured simultaneously over
      a broad spectral range (UV-VIS-IR). The optimum film thickness, the optimum angle
      of incidence, and the effect of light-beam deviation on the measured input Stokes
      parameters are considered.

PMID- 18319863
TI  - Optical roughness measurements with fringe projection.
AB  - The characterization of roughness of engineering surfaces over an area is an
      important task for different applications as well as for manufacturing processes.
      The surface roughness is in particular an important factor in determining the
      performance of a workpiece. We demonstrate that the fringe projection technique
      allows very fast three-dimensional surface inspections. The inspection time for
      an entire measurement is reduced to less than 5 s with standard hardware. Based
      on a zoom stereo microscope setup, we demonstrate a modular measuring instrument.
      The magnification-dependent vertical resolution can be as high as 0.1 microm. The
      special properties for roughness measurements are demonstrated, especially the
      comparability with a tactile sensor and with other optical sensors, which is
      discussed in connection with amplitude parameters.

PMID- 18319864
TI  - Measurement of absolute displacement by a double-modulation technique based on a
      Michelson interferometer.
AB  - A novel method is presented for of measuring absolute displacement with a
      synthesized wavelength interferometer. The optical phase of the interferometer is
      simultaneously modulated with a frequency-modulated laser diode and optical path
      length difference. The error signal originating from the intensity modulation of
      the source is eliminated by a signal processing circuit. In addition, a lock-in
      technique is used to demodulate the envelope of the interferometric signal. The
      displacement signal is derived by the self-mixing technique.

PMID- 18319865
TI  - Absolute-length determination of a long-baseline Fabry-Perot cavity by means of
      resonating modulation sidebands.
AB  - A new method has been demonstrated for absolute-length measurements of a long
      baseline Fabry-Perot cavity by use of phase-modulated light. This method is based
      on determination of a free spectral range (FSR) of the cavity from the frequency
      difference between a carrier and phase-modulation sidebands, both of which
      resonate in the cavity. Sensitive response of the Fabry-Perot cavity near
      resonant frequencies ensures accurate determination of the FSR and thus of the
      absolute length of the cavity. This method was applied to a 300-m Fabry-Perot
      cavity of the TAMA gravitational wave detector that is being developed at the
      National Astronomical Observatory, Tokyo. With a modulation frequency of
      approximately 12 MHz, we successfully determined the absolute cavity length with
      resolution of 1 microm (3 x 10(-9) in strain) and observed local ground strain
      variations of 6 x 10(-8).

PMID- 18319866
TI  - Influence of the director field structure on extinction and scattering by a
      nematic liquid-crystal droplet.
AB  - On the basis of calculations under the discrete dipole approximation and a
      proposed extended model of nested ellipsoids for bipolar droplets, the changes in
      optical properties of a spherical liquid-crystal droplet, caused by a change in
      director configuration under the influence of an external field, have been
      considered.

PMID- 18319867
TI  - Direct ray aberration estimation in Hartmanngrams by use of a regularized phase
      tracking system.
AB  - The Hartmann test is a well-known technique for testing large telescope mirrors.
      The Hartmann technique samples the wave front under analysis by use of a screen
      of uniformly spaced array of holes located at the pupil plane. The traditional
      technique used to gather quantitative data requires the measurement of the
      centroid of these holes as imaged near the paraxial focus. The deviation from its
      unaberrated uniform position is proportional to the slope of the wave-front
      asphericity. The centroid estimation is normally done manually with the aid of a
      microscope or a densitometer; however, newer automatic fringe-processing
      techniques that use the synchronous detection technique or the Fourier phase
      estimation method may also be used. Here we propose a new technique based on a
      regularized phase-tracking (RPT) system to detect the transverse aberration in
      Hartmanngrams in a direct way. That is, it takes the dotted pattern of the
      Hartmanngram as input, and as output the RPT system gives the unwrapped
      transverse ray aberration in just one step. Our RPT is compared with the
      synchronous and the Fourier methods, which may be regarded as its closest
      competitors.

PMID- 18319868
TI  - Fabrication and measurement of optics for the laser interferometer gravitational
      wave observatory.
AB  - The manufacture and testing of high-precision optical surfaces for the Laser
      Interferometer Gravitational Wave Observatory is described. Through the use of
      carefully shaped polishing laps made of a nondeformable polymer material coated
      on a rigid base, surfaces 250 mm in diameter with radii of curvature between 7
      and 15 km were polished to an accuracy of several hundred meters in the curvature
      and with low values of waviness and microroughness. Metrology instrumentation
      used to measure the optical finish included a large-aperture digital
      interferometer calibrated to nanometer-level accuracy for measurements of
      curvature, astigmatism, and waviness and an interference microscope for
      measurements of microroughness. The power spectra of the data from both
      instruments were in good agreement.

PMID- 18319869
TI  - Loss factors of mirrors for a gravitational wave antenna.
AB  - Low-loss mirrors fabricated by ion-beam-sputtering machines for possible
      application in an interferometric gravitational wave antenna were evaluated by
      use of Nd:YAG laser light (lambda = 1064 nm) with two distinct measurements: a
      tabletop experiment that used a short cavity with a small beam with a beam waist
      of approximately 2w(0) = 0.82 mm, and an optical test that used a 20-m
      prototypical gravitational-wave detector with a large beam with a beam waist of
      approximately 2w(0) = 4.4 mm. A multilayer coating comprised 29 layers of
      SiO(2)/Ta(2)O(5) and one protective coating of SiO(2). The best values obtained
      as a result of these measurements were 16 ppm (parts in 10(6)) and 30 ppm in
      total loss, respectively. Also, a two-dimensional loss map generated by use of a
      small beam successfully revealed the existence of a loss structure within the
      coating surface. These results imply that a high-reflectance multilayer coating
      has some inhomogeneities and a loss distribution with a typical scale of a few
      millimeters and that the total measured losses depend on the beam spot size.

PMID- 18319870
TI  - Surface roughness from highlight structure.
AB  - Highlights are due to specular reflection and cause the lustrous or mirrorlike
      appearance of many material surfaces. We investigated in detail the structure of
      highlight patterns that are due to material surface roughness. We interpret
      results in terms of a simple model of a random Gaussian surface. The model's
      prediction corresponds with the microscopic measurement within a factor of 2. The
      method allows one to rank generally the roughness of the surfaces of the fruit
      samples by purely optical means. This simple procedure for estimating surface
      roughness from images has implications for visual perception and graphic
      rendering.

PMID- 18319871
TI  - Band-integrated infrared absorptance of low-molecular-weight paraffin
      hydrocarbons at high temperatures.
AB  - The spectral absorptance of the 3.4-microm band of methane, ethane, propane, and
      butane has been measured with a Fourier transform infrared spectrometer over a
      range of temperatures from 296 to 900 K. The measurements were made at a 4-cm(-1)
      resolution and integrated over the entire band to give the total absorptance. The
      total absorptance is found to behave in such a way that it can be correlated by a
      combination of algebraic expressions that depend on the gas temperature and
      concentration. Average discrepancies between the correlations and the
      measurements are less than 4%, with maximum differences of no greater than 17%.
      In addition, the correlations presented here for methane are shown to be in good
      agreement with established models. Expressions given for the integrated intensity
      of each gas show an inverse dependence on temperature, reflecting the associated
      change in density.

PMID- 18319872
TI  - Polarization properties and fractional-power analysis of coated and uncoated
      parallel-slab multireflection beam splitters.
AB  - The polarization properties of coated and uncoated parallel-slab multireflection
      beam splitters are investigated. In a recent study [Opt. Lett. 21, 1709 (1996)]
      it was shown that the parallel-slab beam splitter is a basic optical component of
      the parallel-slab division-of-amplitude photopolarimeter. The ellipsometric
      parameters and the fractional powers for multireflected components generated by
      this system are analyzed. Interesting new observations with respect to the
      polarization properties at the Brewster angle of incidence and the distribution
      of powers among the multireflected components are presented.

PMID- 18319873
TI  - Discrete thin-film thickness-modulated designs: spacing of all possible
      stopbands.
AB  - The spectral spacing of multiple, high-reflectance stopbands is determined
      analytically for discrete thin-film layer-thickness-modulated designs. Discrete,
      sinusoidal modulation of layer thickness produces unique multilayer designs for
      fundamental modulation frequencies within the range 0 < f(m)<or= 0.5. Thickness
      modulated designs typically have several high-reflectance stopbands at spectral
      frequencies that are a function of modulation frequency. All stopbands were
      verified by the trace of the characteristic matrix for each thickness-modulated
      design. A universal stopband equation is presented that predicts the relative
      spectral spacing of all possible stopbands for thickness-modulated designs. Two
      harmonic components of thickness-modulated designs are defined. The spectral
      performance (stopband position) is shown graphically for modulation amplitudes
      0.25, 0.5, 0.75, 1.0, and 0 < f(m) <or= 0.5.

PMID- 18319874
TI  - Multicomponent blood analysis by near-infrared Raman spectroscopy.
AB  - We demonstrate the use of Raman spectroscopy to measure the concentration of many
      important constituents (analytes) in serum and whole blood samples at
      physiological concentration in vitro across a multipatient data set. A near
      infrared (830-nm) diode laser generates Raman spectra that contain superpositions
      of Raman signals from different analytes. Calibrations for glucose, cholesterol,
      urea, and other analytes are developed by use of partial least-squares cross
      validation. We predict six analytes in serum with significant accuracy in a 66
      patient data set, using 60-s spectra. The calibrations are shown to be fairly
      robust against system drift over the span of seven weeks. In whole blood, a
      preliminary analysis yields accurate predictions of some of the same analytes and
      also hematocrit. The results hold promise for potential medical applications.

PMID- 18319875
TI  - Development of a time-domain optical mammograph and first in vivo applications.
AB  - We have developed a laser-pulse mammograph capable of recording optical
      mammograms within approximately 3 min by measuring time-resolved transmittance at
      each of typically 1500 scan positions, 2.5 mm apart. As a first application two
      patients who have tumors were investigated successfully. From measured
      distributions of times of flight of photons corrected for edge effects we derived
      (1) characteristic quantities, such as photon counts in selected time windows, to
      generate optical mammograms; (2) effective transport scattering and absorption
      coefficients of breast tissue at each scan position, assuming the breast to be
      homogeneous; and (3) optical properties of a selected tumor by applying the
      theory of diffraction of photon density waves by spherical inhomogeneity.
      Mammograms recorded at different lateral offsets between source and detector
      fiber were used to estimate the depth of inhomogeneities.

PMID- 18319876
TI  - Monte carlo simulation of converging laser beams propagating in biological
      materials.
AB  - A new method of Monte Carlo simulation has been developed to simulate the spatial
      distribution of photon density of converging laser beams propagating in a turbid
      medium such as the phantom of biological tissue. This method can be used to
      obtain steady-state light distribution in the tissue phantom for a continuous
      wave laser beam. We have calculated the steady-state distribution of the photon
      density and found important features that are uniquely related to the propagation
      of the converging beams in the tissue phantom.

PMID- 18319877
TI  - Spatially variant regularization improves diffuse optical tomography.
AB  - Diffuse tomography with near-infrared light has biomedical application for
      imaging hemoglobin, water, lipids, cytochromes, or exogenous contrast agents and
      is being investigated for breast cancer diagnosis. A Newton-Raphson inversion
      algorithm is used for image reconstruction of tissue optical absorption and
      transport scattering coefficients from frequency-domain measurements of modulated
      phase shift and light intensity. A variant of Tikhonov regularization is examined
      in which radial variation is allowed in the value of the regularization
      parameter. This method minimizes high-frequency noise in the reconstructed image
      near the source-detector locations and can produce constant image resolution and
      contrast across the image field.

PMID- 18319878
TI  - Diffractive optics and micro-optics: introduction to the feature issue.
AB  - This issue of Applied Optics features 16 papers related to the fabrication,
      design, and application of diffractive and micro-optical elements. A companion
      feature in the Journal of the Optical Society of America A [J. Opt. Soc. Am. A
      16(5), 1091 (1999)] includes papers on the modeling of diffractive elements.

PMID- 18319879
TI  - Mass-transport fabrication of off-axis and prismatic gallium phosphide optics.
AB  - Refractive prismatic and off-axis micro-optical elements have been fabricated in
      gallium phosphide by mass-transport smoothing of multistep and binary preforms,
      respectively. A total optical efficiency of greater than 94% was measured for the
      prism, while diffraction-limited collimation and steering were demonstrated with
      the off-axis lens. A qualitative discussion of possible errors in binary preform
      etching and their effects on the surface figure is also included.

PMID- 18319880
TI  - Fabrication of microprisms for planar optical interconnections by use of analog
      gray-scale lithography with high-energy-beam-sensitive glass.
AB  - For an integrated free-space optical interconnection system we suggest the use of
      microprisms to achieve large coupling angles at low loss. Prisms were fabricated
      in photoresist and quartz glass by analog lithography. High-energy-beam-sensitive
      glass was used as the gray-tone mask. Optical testing of the prisms shows
      acceptable surface quality and high efficiency (95%).

PMID- 18319881
TI  - Ultraviolet-cured polymer microlens arrays.
AB  - A method for fabricating microlens arrays that uses the contraction effect of UV
      curable photopolymers is presented. Lenses with diameters ranging from 0.2 to 2
      mm that were made under different conditions are optically evaluated. The optimum
      conditions for producing low f-number lenses are discussed.

PMID- 18319882
TI  - Beam redirection and frequency filtering with transparent elastomeric diffractive
      elements.
AB  - A new, to our knowledge, type of optical device capable of beam redirection and
      frequency filtering is described. It is based on a transparent elastomeric binary
      diffraction grating. When light is passed through the device the intensities of
      the diffraction orders can be modulated by compression of the elastomer in the
      direction perpendicular to the plane of the grating. Selective filtering of the
      component frequencies of two-component light (lambda = 543.5 nm and lambda =
      632.8 nm) has been demonstrated. Experimental observations are in agreement with
      theoretical calculations quantifying the performance of the device.

PMID- 18319883
TI  - Efficiency-enhanced third-order grating coupler.
AB  - A third-order grating coupler with a grating period 3 times that of a first-order
      grating is discussed in terms of efficiency enhancement. A reflection film is
      integrated between the optical buffer layer and the substrate beneath the grating
      guiding core. The power-distribution ratio for each diffracted wave depends on
      the optical buffer layer's thickness because of interference effects. The
      thickness is determined to suppress first- and second-order diffraction and to
      enhance the power distribution to the output air-radiation wave generated by
      third-order diffraction. A demonstrator was designed and examined at a wavelength
      of 0.82 microm. The measured output coupling efficiency was 40%, whereas the
      theoretical prediction was 60%.

PMID- 18319884
TI  - Reflection-type multiorder grating lens for three ultraviolet wavelengths.
AB  - Utilization of second-, third-, and fourth-order diffraction is discussed for
      providing a single reflection grating lens that yields the same wave-front
      conversions for wavelengths of 420, 280, and 210 nm, which are used to sense
      NO(x) and SO(2) gas densities. A blazed grating lens was fabricated by a planar
      process and characterized by use of UV lamps. The same wave-front conversion was
      observed at the three UV wavelengths. Efficiencies were measured to be 80%, 70%,
      and 30% for second-, third-, and fourth-order diffractions, respectively, at
      wavelengths of 420, 280, and 210 nm, respectively.

PMID- 18319885
TI  - Multiwavelength operation with thin diffractive elements.
AB  - It is generally accepted that diffractive elements designed for multiwavelength
      operation require deep surface-relief profiles. We show, however, that thin
      diffractive elements can be designed to operate with more than one wavelength. A
      novel, to our knowledge, optimization technique is introduced for this purpose.
      The maximum phase delay is limited to only a few multiples of 2pi, and the
      element can implement different functions for different wavelengths. Examples
      with fan-out gratings are discussed.

PMID- 18319886
TI  - Holographic diffractive collimators based on recording with homocentric diverging
      beams for diode lasers.
AB  - A single collimating transmission off-axis blazed surface-relief holographic
      diffractive element that corrects the ellipticity and the astigmatism of a diode
      laser beam was designed. The procedure was applied to a hypothetical laser
      operating at a wavelength of 633 nm that possesses extremely large astigmatism
      and relatively small ellipticity together with small diverging angles of the
      laser beam. The element was recorded with only homocentric diverging beams that
      had pure spherical wave fronts. Because of the off-axis nature of the element,
      the aberration of asymmetry had to be corrected. The element was tested in a
      reciprocal way when the incident wave was a collimated He-Ne laser beam. A
      diffraction-limited beam was obtained that was as large as approximately half of
      the designed aperture.

PMID- 18319887
TI  - Simplified intracavity phase plates for increasing laser-mode discrimination.
AB  - Recently, a new class of laser resonators was introduced that utilizes
      diffractive mirrors and an additional intracavity diffractive phase element. High
      modal discrimination and low fundamental-mode loss were achieved simultaneously
      by use of sinusoidal and pseudorandom diffractive phase elements. An intracavity
      phase element consisting of a simple single-step phase modulation is approximated
      by a Gaussian with a small radius. Explicit expressions are obtained for the
      modal-discrimination factor as a function of resonator parameters with a Gaussian
      output mirror. Numerical simulations are performed for a phase element with a
      step singularity in the phase function, the fundamental mode of this cavity being
      super-Gaussian. The modal discrimination of the cavity is studied for different
      radii of the single-step phase modulation, the position of the phase plate, and
      the cavity Fresnel number. Optimum solutions are found for a plane output mirror
      with either a striped or a circular shape.

PMID- 18319888
TI  - Spatial-mode control of vertical-cavity lasers with micromirrors fabricated and
      replicated in semiconductor materials.
AB  - Micromirrors were fabricated in gallium phosphide by mass transport to provide
      spatial-mode control of vertical-cavity surface-emitting lasers (VCSEL's). The
      concave mirrors were used in an external-cavity configuration to provide spatial
      filtering in the far field. Single-mode cw lasing was demonstrated in 15-microm
      diameter VCSEL's with currents as high as 6 times threshold. The fabrication
      process was extended to micromirrors in gallium arsenide by use of a replication
      and dry-etch transfer process.

PMID- 18319889
TI  - Fabrication of a multichannel wavelength-division multiplexing-passive optical
      net demultiplexer with arrayed-waveguide gratings and diffractive optical
      elements.
AB  - A novel, to our knowledge, integrated wavelength-division multiplexing-passive
      optical net demultiplexer that uses an arrayed-waveguide grating and diffractive
      optical elements is presented. The demultiplexer is used to distribute 1.3-microm
      wavelength signals and to multiplex an eight-channel wavelength-division
      multiplexer spectrum at a 1.55-microm wavelength. The device shows high
      functionality and good optical performance. The measured cross talk was less than
      -21 dB, and the 3-dB bandwidth was determined to be 97 GHz, which is close to the
      theoretical value of 93 GHz. Average losses of 4.5 and 8 dB were measured for the
      1.3- and the 1.55-microm signals, respectively.

PMID- 18319890
TI  - Path-reversed substrate- guided-wave optical interconnects for wavelength
      division demultiplexing.
AB  - A path-reversed substrate-guided-wave holographic interconnection scheme is
      investigated for a wavelength-division demultiplexing application. Using a
      beveled edge of a waveguiding plate allows optical signals to be coupled into the
      waveguiding plate and then to be coupled out of the plate by a waveguide
      hologram. Theoretical analyses are given for dispersion, bandwidth, and recording
      parameters of various guided-wave holographic gratings. A device is fabricated
      with a 45 degrees incident angle and a 45 degrees diffraction angle by use of a
      20-microm photopolymer film. The 3-dB bandwidth of the device is measured to be
      20 nm. Four-channel wavelength demultiplexing is demonstrated at 796, 798, 800,
      and 802 nm with no cross talk observed. A one-to-five cascaded four-channel
      wavelength-division demultiplexer with +/-5% energy uniformity under s
      polarization is also demonstrated to increase the user-sharing capacity. Twenty
      fan-out channels (5 x 4) are achieved experimentally.

PMID- 18319891
TI  - Waveguide-hologram-based wavelength-multiplexed pseudoanalog true-time-delay
      module for wideband phased-array antennas.
AB  - A pseudoanalog true-time-delay (TTD) module based on substrate-guided waves and
      wavelength-division multiplexing is presented. A 1-to-32 (5-bit) even fan-out is
      demonstrated by use of a two-dimensional waveguide hologram array. This module
      has a packing density of 2.5 lines/cm(2) and very compact packaging (8 cm x 4 cm
      x 8 mm). It also reduces TTD system complexity by providing continuously tuned
      delay signals to parallel-control the whole phased-array antenna system. The
      device has a measured bandwidth of as high as 2.4 THz. The delay signal can range
      from tens of picoseconds to several nanoseconds.

PMID- 18319892
TI  - Binary zone-plate array for a parallel joint transform correlator applied to face
      recognition.
AB  - Taking advantage of small aberrations, high efficiency, and compactness, we
      developed a new, to our knowledge, design procedure for a binary zone-plate array
      (BZPA) and applied it to a parallel joint transform correlator for the
      recognition of the human face. Pairs of reference and unknown images of faces are
      displayed on a liquid-crystal spatial light modulator (SLM), Fourier transformed
      by the BZPA, intensity recorded on an optically addressable SLM, and inversely
      Fourier transformed to obtain correlation signals. Consideration of the bandwidth
      allows the relations among the channel number, the numerical aperture of the zone
      plates, and the pattern size to be determined. Experimentally a five-channel
      parallel correlator was implemented and tested successfully with a 100-person
      database. The design and the fabrication of a 20-channel BZPA for phonetic
      character recognition are also included.

PMID- 18319893
TI  - Stray-light effects of diffractive beam-shaping elements in optical microsystems.
AB  - The use of diffractive beam-shaping elements in hybrid or monolithic microsystems
      is investigated. Compact optical systems require diffractive structures with
      small grating periods for creating large deflection angles. Such elements are
      difficult to fabricate while a low stray-light level is maintained. In addition,
      because of the small geometrical dimensions and the short propagation lengths in
      an optomechanical microsystem, any stray light generated by the diffractive
      structure critically affects the overall optical performance. A model for the
      estimation of the interference effects between the designed and the unwanted
      diffraction orders is developed and applied to an example of a collimating
      diffractive optical element. On the basis of theoretical and experimental
      results, design rules for the application of diffractive beam-shaping elements in
      microsystems are derived.

PMID- 18319894
TI  - Design and analysis of a diffractive optical filter for use in an optoelectronic
      error-diffusion neural network.
AB  - The design, fabrication, experimental characterization, and system-performance
      analysis of a diffractive optical implementation of an error-diffusion filter for
      use in digital image halftoning is reported. A diffractive optical filter was
      fabricated as an eight-level phase element that diffuses the quantization error
      nonuniformly in both the weighting and the spatial dimensions, according to a
      prescribed algorithm. Ten identical diffractive elements were fabricated on ten
      different wafers and subsequently characterized experimentally. A detailed error
      analysis including both fabrication and instrumentation errors was carried out to
      quantify the performance of the fabrication process as well as the expected
      system performance of the filters. Halftone system performance was evaluated by
      use of the experimental filter's performance and both quantitative and
      qualitative performance metrics. The results of this analysis demonstrate that
      multiple identical copies of a diffractive optical filter can be produced with
      sufficient accuracy that no loss in the halftoning system performance results.

PMID- 18319895
TI  - Polarized pseudonondiffracting beams generated by polarization-selective
      diffractive phase elements.
AB  - The concept and the generation of polarized pseudonondiffracting beams (PNDB's)
      from polarization-selective diffractive phase elements (DPE's) are presented for
      what we believe is the first time in a monochromatic illuminating system. The
      polarized PNDB's behave as segmented almost constant axial-intensity
      distributions with individual different polarization states in different
      segments. The pure polarization state in each segment can be arbitrarily preset.
      The design of polarization-selective DPE's is achieved with the use of the
      conjugate-gradient method. The simulation results show that the DPE's we designed
      can successfully implement the desired polarization modulation. Furthermore the
      PNDB's characteristics of axial-intensity uniformity and beamlike shape are well
      achieved with the DPE's we designed.

PMID- 18319896
TI  - Disk-type multiplex holography.
AB  - A theory for making a disk-type multiplex hologram is derived. This theory
      relates the final image point, as seen by the observer, to a point on the
      original three-dimensional object through a set of equations. From these
      equations the distortion of the image and the wavelength as seen by each
      individual eye can be evaluated. Computer simulation shows the characteristics of
      this hologram. Some experimental results also confirm these characteristics. By
      reversing the process and specifying a desired image, we generated a set of
      distorted two-dimensional originals. The hologram fabricated with these distorted
      images can generate nearly distortion-free images.

PMID- 18319897
TI  - Multichannel acousto-optic Bragg cell for real-time electroholography.
AB  - A multichannel acousto-optic Bragg cell was made by the joining of acousto-optic
      cells that have the shape of symmetrical trapezoidal prisms. This acousto-optic
      Bragg cell has an aperture length equal to the sum of its component acousto-optic
      cells but has an aperture time equal to that of each acousto-optic cell. We
      tested the performance of the multichannel acousto-optic Bragg cell by joining
      six TeO(2) acousto-optic cells together with 300-microm gaps between one another.
      The holographic fringe data prepared by computer were divided into six equal
      segments. Each data segment was again divided into six equal parts and then fed
      into the corresponding acousto-optic cell. The holographic images were
      reconstructed by the periodical illumination of a green (lambda = 0.5145 microm)
      pulse laser beam onto the multichannel acousto-optic Bragg cell. The
      reconstructed images are sharp and clear. This indicates that the multichannel
      acousto-optic Bragg cell is working properly.

PMID- 18319898
TI  - Two-dimensional optical architectures for the receive mode of phased-array
      antennas.
AB  - We propose and experimentally demonstrate two optical architectures that process
      the receive mode of a p x p element phased-array antenna. The architectures are
      based on free-space propagation and switching of the channelized optical carriers
      of microwave signals. With the first architecture a direct transposition of the
      received signals in the optical domain is assumed. The second architecture is
      based on the optical generation and distribution of a microwave local oscillator
      matched in frequency and direction. Preliminary experimental results at microwave
      frequencies of approximately 3 GHz are presented.

PMID- 18319899
TI  - Experimental revealing of polarization waves.
AB  - Stationary and traveling waves of the states of optical polarization are
      considered in the framework of Jones vector formalism. The feasibility of
      revealing these waves in holographic and interference arrangements is
      substantiated and demonstrated.

PMID- 18319900
TI  - Atmospheric ray path modeling for radiative transfer algorithms.
AB  - A new method for the determination of ray paths as well as resulting path
      segments and partial gas columns within a layered atmosphere is presented. Any
      singularity at the tangent point is avoided. No use is made of the gross
      spherical symmetry of the Earth's atmosphere. Using this approach we examine the
      impact of the Earth's oblate shape and horizontal atmospheric inhomogeneities on
      infrared limb spectra.

PMID- 18319901
TI  - Multiple scattering of a photon flux: implications for the integral average
      cosine of the underwater light field.
AB  - It is shown that where micros is the average cosine of scattering, then for any
      set of photons that undergoes exactly n scatterings per photon, the average
      cosine after scattering is micro(0)micro(s)(n), where micro(0) is the average
      cosine of the photon flux before scattering. For a set of photons that has
      traversed distance d through a medium with scattering coefficient b, the average
      cosine is micro(0) exp[-bd(1 - micro(s))]. For water bodies in which loss of
      upward-scattered photons through the surface is small enough to be disregarded,
      the value of micro(c) (the average cosine of all the photons instantaneously
      present in the water column) for any given incoming flux of photons with average
      cosine micro(0) is determined entirely by the inherent optical properties of the
      water in accordance with micro(c)= micro(0)/[1 + (b/a)(1 - micro(s))], where a
      and b are the absorption and scattering coefficients.

PMID- 18319902
TI  - Finite-difference time-domain solution of light scattering by dielectric
      particles with a perfectly matched layer absorbing boundary condition.
AB  - A three-dimensional finite-difference time-domain (FDTD) program has been
      developed to provide a numerical solution for light scattering by nonspherical
      dielectric particles. The perfectly matched layer (PML) absorbing boundary
      condition (ABC) is used to truncate the computational domain. As a result of
      using the PML ABC, the present FDTD program requires much less computer memory
      and CPU time than those that use traditional truncation techniques. For spheres
      with particle-size parameters as large as 40, the extinction and absorption
      efficiencies from the present FDTD program match the Mie results closely, with
      differences of less than approximately 1%. The difference in the scattering phase
      function is typically smaller than approximately 5%. The FDTD program has also
      been checked by use of the exact solution for light scattering by a pair of
      spheres in contact. Finally, applications of the PML FDTD to hexagonal particles
      and to spheres aggregated into tetrahedral structures are presented.

PMID- 18319903
TI  - Nondiffracting narrow light beam with small atmospheric turbulence-influenced
      propagation.
AB  - A narrow light beam that propagates in the atmosphere with less disturbance than
      conventional light beams is introduced. The operating method and features of the
      newly proposed long-range nondiffracting beam (LRNB) are briefly demonstrated.
      Some experimental results of the atmospheric propagation of this beam at a
      distance of 500 m are shown in comparison with a conventional collimated beam and
      a focused beam. The results and related analyses show that the LRNB is much less
      influenced by atmospheric turbulence than other beams and suggest that the LRNB
      can apply to many fields.

PMID- 18319904
TI  - Degree of linear polarization in spectral radiances from water-viewing infrared
      radiometers.
AB  - Infrared radiances from water become partially polarized at oblique viewing
      angles through both emission and reflection. I describe computer simulations that
      show how the state of polarization for water varies with environmental conditions
      over a wavelength range of 3-15 microm with 0.05-microm resolution. Polarization
      at wavelengths longer than approximately 4 microm generally is negative (p, or
      vertical) and increases with incidence angle up to approximately 75 degrees,
      beyond which the horizontally polarized reflected atmospheric radiance begins to
      dominate the surface emission. The highest p polarization (approximately 4-10%)
      is found in the atmospheric window regions of approximately 4-5 and 8-14 microm.
      In the 3-5-microm spectral band, especially between 3 and 4 microm, reflected
      atmospheric radiance usually is greater than surface emission, resulting in a net
      s polarization (horizontal). The results of these simulations agree well with
      broadband measurements of the degree of polarization for a water surface viewed
      at nadir angles of 0-75 degrees.

PMID- 18319905
TI  - Contribution of Raman scattering to water-leaving radiance: a reexamination.
AB  - We have reexamined the contribution of Raman scattering to the water-leaving
      radiance in case 1 waters by carrying out radiative transfer simulations that
      combine the latest reported measurements of the absorption coefficient of pure
      water with direct measurements of the spectral variation of the Raman-scattering
      coefficient. The resulting contribution of Raman scattering is then compared with
      experimental measurements of the water-leaving radiance, and the fractional
      contribution of radiance produced by Raman scattering to the total radiance
      measured at a given wavelength is determined. The results show that (1) the
      contribution of Raman scattering to the water-leaving radiance in an ocean of
      pure seawater is as much as 50-100% larger than earlier predictions, and (2) the
      Raman contribution does not decay as rapidly with increasing concentrations of
      chlorophyllouslike pigments C as predicted earlier. In fact, the Raman fraction
      for C <or= 1 mg/m(3) is approximately >8% at wavelengths of interest in ocean
      color remote sensing and therefore cannot be ignored in ocean color modeling.

PMID- 18319906
TI  - Lidar inversion of atmospheric backscatter and extinction-to-backscatter ratios
      by use of a Kalman filter.
AB  - A first inversion of the backscatter profile and extinction-to-backscatter ratio
      from pulsed elastic-backscatter lidar returns is treated by means of an extended
      Kalman filter (EKF). The EKF approach enables one to overcome the intrinsic
      limitations of standard straightforward nonmemory procedures such as the slope
      method, exponential curve fitting, and the backward inversion algorithm. Whereas
      those procedures are inherently not adaptable because independent inversions are
      performed for each return signal and neither the statistics of the signals nor a
      priori uncertainties (e.g., boundary calibrations) are taken into account, in the
      case of the Kalman filter the filter updates itself because it is weighted by the
      imbalance between the a priori estimates of the optical parameters (i.e., past
      inversions) and the new estimates based on a minimum-variance criterion, as long
      as there are different lidar returns. Calibration errors and initialization
      uncertainties can be assimilated also. The study begins with the formulation of
      the inversion problem and an appropriate atmospheric stochastic model. Based on
      extensive simulation and realistic conditions, it is shown that the EKF approach
      enables one to retrieve the optical parameters as time-range-dependent functions
      and hence to track the atmospheric evolution; the performance of this approach is
      limited only by the quality and availability of the a priori information and the
      accuracy of the atmospheric model used. The study ends with an encouraging
      practical inversion of a live scene measured at the Nd:YAG elastic-backscatter
      lidar station at our premises at the Polytechnic University of Catalonia,
      Barcelona.

PMID- 18319907
TI  - Retrieval of aerosol profile variations from reflected radiation in the oxygen
      absorption a band.
AB  - Through a Fredholm integral equation of the first kind, aerosol kernel functions
      relate the variations in radiance measured by satellites to the variations in the
      aerosol extinction profile and thus permit profile retrieval from radiance
      measurements by inversion of the set of radiative transfer equations for various
      spectral intervals. Previously [Appl. Opt. 36, 1328 (1997)] the kernel functions
      were evaluated for the red and near-infrared spectral regions outside molecular
      absorption bands. Here they are computed within the oxygen A band with 20-cm(-1)
      spectral resolution. It is shown that, even with such a relatively low spectral
      resolution, the new set of kernels is able to provide better information on and
      improved accuracy of the retrieved profile.

PMID- 18319908
TI  - Reciprocity principle applicable to reflected radiance measurements and the
      searchlight problem.
AB  - In a recent paper by Di Girolamo et al. [J. Geophys. Res. D 103, 8795 (1998)] a
      heuristic argument was used to derive a reciprocity principle applicable to
      reflected solar radiation measurements. Here a formal derivation of this
      reciprocity principle is presented. It is also demonstrated that a purely spatial
      reciprocal relationship exists between one-dimensional radiative transfer theory
      and the three-dimensional searchlight problem for horizontally homogeneous media.

PMID- 18319909
TI  - Algorithms for ocean-bottom albedo determination from in-water natural-light
      measurements.
AB  - A method for determining the ocean-bottom optical albedo R(b) from in-water
      upward and downward irradiance measurements at a shallow site is presented,
      tested, and compared with a more familiar approach that requires additional
      measurements at a nearby deep-water site. Also presented are two new algorithms
      for estimating R(b) from measurements of the downward irradiance and vertically
      upward radiance. All methods performed well in numerical situations at depths at
      which the influence of the bottom on the light field was significant.

PMID- 18319910
TI  - Effect of temperature on the absorption loss of chalcogenide glass fibers.
AB  - The change in the absorption loss of IR-transmitting chalcogenide glass fibers in
      the temperature range of -90 degrees C <or= T <or= 70 degrees C was investigated.
      For sulfur-based glass fibers the change in loss relative to room temperature was
      slightly affected by the temperature in the wavelength region of 1-5 microm. For
      lambda >or= 6 microm the change in loss was mainly due to multiphonon absorption.
      The change in loss for tellurium-based glass fibers increased significantly at T
      = 60 degrees C. The increase in the loss at short wavelengths (lambda <or= 4.1
      microm) was due to electronic excitations in the tail states. Between 5 and 9
      microm there was noticeable free-carrier absorption. Beyond lambda >or= 9 microm,
      multiphonon absorption dominated the loss spectrum.

PMID- 18319911
TI  - General formula for coupling-loss characterization of single-mode fiber
      collimators by use of gradient-index rod lenses.
AB  - A general formula for determining the coupling loss between two single-mode fiber
      collimators with the simultaneous existence of separation, lateral offset and
      angular tilt misalignments, and spot-size mismatch is theoretically derived by
      use of the Gaussian field approximation. Based on this general formula, the
      formulas for coupling losses that are due to the misalignment of insert
      separation, lateral offset, and angular tilt are given. The formula for the
      coupling loss that is due to Gaussian spot-size mismatch of two single-mode
      collimators is also given. Good agreement between these formulas and experimental
      results is demonstrated with gradient-index rod lens-based fiber collimators
      operating in the 1300-nm band.

PMID- 18319912
TI  - Analysis of phase-shifted fiber Bragg gratings written with phase plates.
AB  - A method for obtaining phase-shifted Bragg gratings by use of phase plates is
      presented. A comparison of experimental and theoretical results allows us to
      describe the utility of such a component.

PMID- 18319913
TI  - Power versus stabilization for laser satellite communication.
AB  - To establish optical communication between any two satellites, the lines of sight
      of their optics must be aligned for the duration of the communication. The
      satellite pointing and tracking systems perform the alignment. The satellite
      pointing systems vibrate because of tracking noise and mechanical impacts (such
      as thruster operation, the antenna pointing mechanism, the solar array driver,
      navigation noise, tracking noise). These vibrations increase the bit error rate
      (BER) of the communication system. An expression is derived for adaptive
      transmitter power that compensates for vibration effects in heterodyne laser
      satellite links. This compensation makes it possible to keep the link BER
      performance constant for changes in vibration amplitudes. The motivation for
      constant BER is derived from the requirement for future satellite communication
      networks with high quality of service. A practical situation of a two-low-Earth
      orbit satellite communication link is given. From the results of the example it
      is seen that the required power for a given BER increases almost exponentially
      for linear increase in vibration amplitude.

PMID- 18319914
TI  - Design of microprism-type symmetric Y-junction waveguides with the full phase
      compensation method.
AB  - Using the full phase compensation method, we derive a set of precise phase
      compensation formulas to design a three-dimensional microprism-type Y junction.
      The simulated and traditional results are compared to verify that the proposed
      structure is better. By taking into account the orthogonality principle to
      estimate the branching losses, the proposed structure was improved to better than
      approximately 6-10% over the traditional structure.

PMID- 18319915
TI  - Analysis of an optically controlled photonic switch.
AB  - The principle that the coupling of light between two fiber waveguides can be
      controlled by the resonant interference of a third waveguide has been developed
      [Attard, Appl. Opt. 37, 2296-2302 (1998)]. Here significant details concerning
      the operation of a photonic switch are obtained, and a more complete analysis is
      presented. Multiple-resonant conditions are identified for slab and fiber control
      waveguides at large indices of refraction. Thus a selection of materials with an
      appropriate refractive index and a Kerr coefficient is rendered more easily.
      Furthermore it is shown that the light used to control the index of refraction in
      the control waveguide does not enter the output of the photonic switch but
      remains confined to the control waveguide, for either a slab or a multimode fiber
      control waveguide. Spatial fluctuations of the control light beam in the control
      waveguide do not affect the operation of the photonic switch. Tolerances have
      been determined for the spacing between the control waveguide and the photonic
      coupler and also for the index of refraction of the control waveguide.

PMID- 18319916
TI  - Experimental investigation of an unstable ring resonator with 90-deg beam
      rotation for a chemical oxygen iodine laser.
AB  - We report the experimental results of an unstable ring resonator with 90-deg beam
      rotation for a kilowatt class chemical oxygen iodine laser (COIL). The
      distributions of near-field phase and far-field intensity were measured. A beam
      quality of 1.6 was achieved when the COIL average output power was approximately
      5 kW.

PMID- 18319917
TI  - Experimental determination of fractional thermal loading in an operating diode
      pumped Nd:YVO4 minilaser at 1064 nm.
AB  - A practical in situ method is described and used for determination of the
      fractional thermal-loading parameter eta(h) in an operating diode-pumped
      Nd:YVO(4) minilaser at 1064 nm. Readily applicable to the thermal
      characterization of other solid-state media, the method is based on the fact that
      thermally induced lensing will cause the laser oscillation to be quenched at a
      critical pump power whose magnitude depends on the cavity configuration, thermo
      optical properties of the gain medium, and, in particular, on the value of
      eta(h). In the experiments described here, a 0.5-mm-long coated Nd:YVO(4) crystal
      with 3-at. % Nd concentration was used to construct the diode-pumped laser with a
      flat highly reflecting end mirror and an intracavity lens. For the method to be
      effective, the resonator was set up close to the edge of the stability range.
      Above the oscillation threshold, the pump power at which lasing was quenched
      because of the onset of the thermally induced resonator instability was measured
      as a function of the intracavity lens position. A numerical model that accounted
      for absorption saturation and pump-induced thermal lensing was then used to
      analyze the experimentally measured data with eta(h) as an adjustable parameter.
      The average best-fit value of eta(h) was determined to be 0.40 with an estimated
      statistical variation of 8%.

PMID- 18319918
TI  - Systematic errors in laser gain, saturation irradiance, and cavity loss
      measurements and comparison with a HCN laser.
AB  - A pair of laser parameters of considerable practical interest are the small
      signal gain and saturation irradiance of the gain medium. These are commonly
      measured by observing the dependence of the output power on some adjustable
      cavity loss parameter and comparing the measured data with the predictions of a
      suitable laser model. Because of the inevitable approximations in this model the
      resulting estimates of gain and saturation irradiance are always affected to some
      extent by systematic errors. The small-gain, plane-wave, mean-field, and pure
      homogeneous or inhomogeneous line-broadening approximations are considered, with
      estimates of the magnitudes of these errors being presented for the case in which
      the gain, the saturation irradiance, and the cavity loss are fitted to the data.
      It is shown that these errors can be quite substantial, and therefore accurate
      absolute measurements of the three laser parameters can be quite difficult to
      obtain using the variable loss method. As an illustration of these errors, a
      comparison between the measured output power from a HCN laser and the power
      predicted using experimentally measured gain and saturation irradiance values is
      shown. The poor quality of these predictions illustrates the serious effects that
      the systematic errors can have, although an alternative analysis in which the
      cavity loss is supplied and only the gain and saturation irradiance fitted is
      also shown and gives good predictions despite inaccuracies in the model.

PMID- 18319919
TI  - Temperature characteristics and stabilization of orthogonal polarization two
      frequency Nd3+:YAG microchip lasers.
AB  - The temperature dependence of the beat frequency and polarization azimuth of
      fiber-guiding laser diode pumped Nd(3+):YAG microchip lasers emitting orthogonal
      linear polarization at two frequencies is investigated, and we found a
      resemblance to the features that result from the application of mechanical force.
      The experimental observations are well described by the cavity model, which
      indicates that temperature change induces weak phase anisotropy in addition to
      the original phase anisotropy with general mutually inclined axes of anisotropy.
      With a servo control to keep the beat frequency constant, the beat and central
      laser frequencies are simultaneously stabilized to within +/-0.1 MHz and +/-0.35
      GHz, respectively.

PMID- 18319920
TI  - Photon-avalanche upconversion in thulium-doped lutetium aluminum garnet.
AB  - Strong blue fluorescence at 487 nm corresponding to the (1)G(4) --> (3)H(6)
      transition was generated from Tm(3+)-doped lutetium aluminum garnet on excitation
      with a 618-nm dye laser as a result of a photon-avalanche upconversion mechanism.

PMID- 18319921
TI  - Theoretical modeling and design of a Tm, Ho:YLiF4 microchip laser.
AB  - We present theoretical modeling that makes it possible to compute the output
      characteristics of a laser-pumped codoped Tm, Ho microchip laser and the
      experimental results already obtained with a Tm, Ho:YLiF(4) crystal. By taking
      into account the match of the pump beam to the self-induced eigenmode of the
      cavity, we find good agreement between theory and experiment when the pump beam
      size is properly adjusted relative to the absorbed pump power and the crystal
      characteristics.

PMID- 18319922
TI  - Thermal coefficients of the expansion and refractive index in YAG.
AB  - The thermal expansion coefficient and dn/dT are measured by interferometry
      techniques in undoped YAG below 300 K. The thermal expansion coefficient at 125 K
      is measured to be 2.70 x 10(-6) K(-1) and dn/dT at 633 nm is 2.5 x 10(-6) K(-1),
      compared with 7 x 10(-6) K(-1) and 9 x 10(-6) K(-1) for these quantities at 300
      K.

PMID- 18319923
TI  - Powerful and tunable operation of a 1-2-kHz repetition-rate gain-switched
      Cr:forsterite laser and its frequency doubling.
AB  - We present a comprehensive study of the optimum operating regime in gain-switched
      Cr:forsterite lasers pumped at kilohertz repetition rates, comparing five
      crystals of similar quality but different dopant levels. The optimization of the
      cavity design includes selection of the proper pump fluence to account for
      excited-state absorption, optimum matching of the pump and laser modes, and
      consideration of thermal effects. As a result >1-W average output power is
      demonstrated at 2 kHz. The maximum conversion efficiencies achieved at 1 kHz are
      24.2% (slope) and 20% (absolute). Narrow-band operation of this laser is possible
      with a birefringent filter, which is a prerequisite for efficient frequency
      doubling to cover the 585-660-nm part of the visible spectral range. Tunable
      second-harmonic generation in a temperature-tuned noncritical scheme that employs
      LiB(3)O(5) produces 60 mW of average power near 619 nm with 13.5% conversion
      efficiency.

PMID- 18319924
TI  - Femtosecond regenerative amplification in Cr:forsterite.
AB  - We describe an oscillator-amplifier laser system for the generation of high-power
      femtosecond pulses near 1.25 microm based on chromium-doped forsterite. Chirped
      pulse amplification at a 1-kHz repetition rate raises the pulse energy to >350
      microJ. The nearly transform-limited 200-microJ, 135-fs-long recompressed pulses
      have a peak power of approximately 1.5 GW.

PMID- 18319925
TI  - Two-dimensional simulation of an unstable resonator with a stable core.
AB  - An optical resonator simulation code based on the idea of a partially coherent
      optical field has been developed and used to optimize the design parameters of an
      unstable resonator with a stable core. The resonator was intended for use with
      low-gain, large-bore lasers, such as the chemical oxygen-iodine laser (COIL).
      First the design parameters of the resonator were optimized by the simulation
      code; then a set of mirrors was fabricated for a small-scale COIL. A 14-W output
      with M(2) = 29 was obtained. The experimentally obtained results were in good
      agreement with calculations.

PMID- 18319926
TI  - Complete characterization of a self-mode-locked ti:sapphire laser in the vicinity
      of zero group-delay dispersion by frequency-resolved optical gating.
AB  - The intensity and the phase of ultrashort pulses from a self-mode-locked
      Ti:sapphire laser operating in the vicinity of zero group-delay dispersion (GDD)
      have been completely characterized by the technique of frequency-resolved optical
      gating (FROG). For small values of negative GDD, the appearance of a dispersive
      wave in the pulse spectrum is manifested in the measured FROG trace, and pulse
      retrieval directly shows its association with a broad leading-edge pedestal. For
      positive GDD, we confirm previous experimental observations of picosecond pulses
      with large positive chirp and report a new operating regime in which the output
      pulses are of picosecond duration but are intensity modulated at 20 THz. The
      physical origin of this modulation is discussed by analogy with similar effects
      observed during pulse propagation in optical fibers, and the experimental results
      are compared with a model of intracavity four-wave mixing about the cavity zero
      GDD wavelength.

PMID- 18319927
TI  - All-prism achromatic phase matching for tunable second-harmonic generation.
AB  - Achromatic phase matching (APM) involves dispersing the light entering a
      nonlinear optical crystal so that a wide range of wavelengths is simultaneously
      phase matched. We constructed an APM apparatus consisting of six prisms, the
      final dispersion angle of which was optimized to match to second order in
      wavelength the type I phase-matching angle of beta barium borate (BBO). With this
      apparatus, we doubled tunable fundamental light from 620 to 700 nm in wavelength
      using a 4-mm-long BBO crystal. An analogous set of six prisms after the BBO
      crystal, optimized to second order in second-harmonic wavelength, realigned the
      output second-harmonic beams. Computer simulations predict that adjustment of a
      single prism can compensate angular misalignment of any or all the prisms before
      the crystal, and similarly for the prisms after the crystal. We demonstrated such
      compensation with the experimental device. The simulations also indicate that the
      phase-matching wavelength band can be shifted and optimized for different crystal
      lengths.

PMID- 18319928
TI  - Synchronously pumped optical parametric oscillation in periodically poled lithium
      niobate with 1-w average output power.
AB  - We report on a rugged all-solid-state laser source of near-IR radiation in the
      range of 1461-1601 nm based on a high-power Nd:YVO(4) laser that is mode locked
      by a semiconductor saturable Bragg reflector as the pump source of a
      synchronously pumped optical parametric oscillator with a periodically poled
      lithium niobate crystal. The system produces 34-ps pulses with a high repetition
      rate of 235 MHz and an average output power of 1 W. The relatively long pulses
      lead to wide cavity detuning tolerances. The comparatively narrow spectral
      bandwidth of <15 GHz is suitable for applications such as pollutant detection.

PMID- 18319929
TI  - Experimental considerations of simultaneous thermal lens and beam deflection
      phenomena.
AB  - A theoretical model, believed to be novel, that describes simultaneous thermal
      lens and beam deflection phenomena was experimentally tested. The effect of beam
      deflection on thermal lens measurements and the effect of the thermal lens on
      beam deflection measurements were investigated. The experiment confirmed the
      validity of theoretical predictions for measurements of strongly absorbing
      samples for which the assumption of an unchanged pump beam in the sample is still
      valid.

PMID- 18319930
TI  - Continuous-wave power transmission and thermal lensing of a saturable absorber
      subject to excited-state absorption.
AB  - Rate-equation analysis has been used in an investigation of the role of
      saturation and excited-state absorption in the power transmission characteristics
      and thermal lensing of an absorber. Use of an iterative approach gives explicit
      analytical results for power transmission and thermal focal length in the
      presence of excited-state absorption. Sample calculations indicate that pump
      absorption can increase or decrease with increasing incident pump power,
      depending on the relative strength of the excited-state absorption cross section
      with respect to the ground-state absorption cross section. In the case of thermal
      lensing, results further indicate that saturation and excited-state absorption
      act as two competing effects, the former reducing the strength of the thermal
      lens and the latter causing the opposite effect. The analytical formulas derived
      in this analysis should prove useful to experimentalists in determination of
      ground-state and excited-state absorption cross sections from experimental power
      transmission and lensing data.

PMID- 18319931
TI  - Laser ablative shaping of plastic optical components for phase control.
AB  - A new scheme for phase control of optical components with laser ablation has been
      developed. One can ablate the surface shape of optical plastic material coated on
      a glass plate by using 193-nm laser light to control the transmission wave front.
      The surface shape is monitored in situ and corrected to attain the desired
      aberration level. The irradiation fluence is approximately 40 mJ/cm(2), and the
      ablation depth/pulse is approximately 0.01 microm/pulse for UV-cured resin. A
      wave-front aberration of 3.0 lambda is reduced to 0.17 lambda for flat surface
      shaping. For spherical surface generation, an aberration of 2.5 lambda is reduced
      to 0.2 lambda. The increase in surface roughness is kept within acceptable
      levels.

PMID- 18319932
TI  - Multilateration with the wide-angle airborne laser ranging system: positioning
      precision and atmospheric effects.
AB  - Numerical simulations based on previously validated models for the wide-angle
      airborne laser ranging system are used here for assessing the precision in
      coordinate estimates of ground-based cube-corner retroreflectors (CCR's). It is
      shown that the precision can be optimized to first order as a function of
      instrument performance, number of laser shots (LS's), and network size. Laser
      beam divergence, aircraft altitude, and CCR density are only second-order
      parameters, provided that the number of echoes per LS is greater than 20. Thus
      precision in the vertical is approximately 1 mm, with a signal-to-noise ratio of
      50 at nadir, a 10-km altitude, a 20 degrees beam divergence, and approximately 5
      x 10(3) measurements. Scintillation and fair-weather cumulus clouds usually have
      negligible influence on the estimates. Laser biases and path delay are
      compensated for by adjustment of aircraft offsets. The predominant atmospheric
      effect is with mesoscale nonuniform horizontal temperature gradients, which might
      lead to biases near 0.5 mm.

PMID- 18319933
TI  - Application of statistical methods to the determination of slope in lidar data.
AB  - Assumptions made in the analysis of both Raman lidar measurements of aerosol
      extinction and differential absorption lidar (DIAL) measurements of an absorbing
      species are tested. Statistical analysis techniques are used to enhance the
      estimation of aerosol extinction and aerosol extinction error that is usually
      handled using a linear model. It is determined that the most probable extinction
      value can differ from that of the linear assumption by up to 10% and that
      differences larger than 50% can occur in the calculation of extinction error.
      Ignoring error in the number density alters the calculated extinction by up to 3%
      and that of extinction error by up to 10%. The preceding results were obtained
      using the least-squares technique. The least-squares technique assumes that the
      data being regressed are normally distributed. However, the quantity that is
      usually regressed in aerosol extinction and DIAL calculations is not normally
      distributed. A technique is presented that allows the required numerical
      derivative to be determined by regressing only normally distributed data. The
      results from this technique are compared with the usual procedure. The same
      concerns raised here regarding appropriate choice of a model in the context of
      aerosol extinction calculations should apply to DIAL calculations of absorbing
      species such as water vapor or ozone as well because the numerical derivative
      that is required is identical.

PMID- 18319934
TI  - Demonstration of a rapidly strain tuned Er3+-doped fiber laser for sensitive gas
      detection.
AB  - We describe a novel combination of a diode-pumped, wavelength-modulated Er(3+)
      doped fiber laser light source with a sensitive noise cancellation circuit for
      detection of acetylene and ammonia. The laser tuning element, a fiber Bragg
      grating, was mounted in such a way that it could be strained controllably and
      rapidly, allowing noise cancellation techniques to be applied to the wavelength
      modulated output of the fiber laser. The experimental setup is relatively simple
      and can be extended to other fiber laser wavelengths for which semiconductor
      lasers are not readily available by selection of a different fiber Bragg grating
      and gain medium.

PMID- 18319935
TI  - Linearization of the frequency sweep of a frequency-modulated continuous-wave
      semiconductor laser radar and the resulting ranging performance.
AB  - The performance of a frequency-modulated continuous-wave (FMCW) semiconductor
      laser radar has been examined. Frequency modulation (linear chirp) has been
      studied experimentally in detail. To create a linear frequency sweep, we modified
      the modulating function according to the measured frequency response of the
      laser, using an arbitrary function generator. The measurements indicate the
      possibility of achieving a spectral width of the signal peak that is transform
      limited rather than limited by the frequency modulation response of the laser,
      which permits the use of a narrow detection bandwidth. The narrow width results
      in a relatively high signal-to-noise ratio for low output power and thus also in
      relatively long-range and high-range accuracy. We have performed measurements of
      a diffuse target to determine the performance of a test laser radar system. The
      maximum range, range accuracy, and speed accuracy for a semiconductor laser with
      an output power of 10 mW and a linewidth of 400 kHz are presented. The influence
      of the laser's output power and coherence length on the performance of a
      semiconductor-laser-based FMCW laser radar is discussed.

PMID- 18319936
TI  - Interference of backscatter from two droplets in a focused continuous-wave CO2
      Doppler lidar beam.
AB  - With a focused continuous-wave CO(2) Doppler lidar at 9.1-microm wavelength, the
      superposition of backscatter from two appromately 14.12-microm-diameter silicone
      oil droplets in the lidar beam produced interference that resulted in a single
      backscatter pulse from the two droplets with a distinct periodic structure. This
      interference is caused by the phase difference in backscatter from the two
      droplets while they are traversing the lidar beam at different speeds, and thus
      the droplet separation is not constant. The complete cycle of interference, with
      periodicity 2pi, gives excellent agreement between measurements and lidar theory.

PMID- 18319937
TI  - Abel inversion of deflectometric measurements in dynamic flows.
AB  - We present an Abel-inversion algorithm to reconstruct mean and rms refractive
      index profiles from spatially resolved statistical measurements of the beam
      deflection angle in time-dependent, axisymmetric flows. An oscillating gas-jet
      diffusion flame was investigated as a test case for applying the algorithm.
      Experimental data were obtained across the whole field by a rainbow schlieren
      apparatus. Results show that simultaneous multipoint measurements are necessary
      to reconstruct the rms refractive index accurately.

PMID- 18319938
TI  - Light backscattering polarization patterns from turbid media: theory and
      experiment.
AB  - We present both experimental measurements and Monte-Carlo-based simulations of
      the diffusely backscattered intensity patterns that arise from illuminating a
      turbid medium with a polarized laser beam. It is rigorously shown that, because
      of axial symmetry of the system, only seven elements of the effective
      backscattering Mueller matrix are independent. A new numerical method that allows
      simultaneous calculation of all 16 elements of the two-dimensional Mueller matrix
      is used. To validate our method we compared calculations to measurements from a
      turbid medium that consisted of polystyrene spheres of different sizes and
      concentrations in deionized water. The experimental and numerical results are in
      excellent agreement.

PMID- 18319939
TI  - Particle sizing in strongly turbid suspensions with the one-beam cross
      correlation dynamic light-scattering technique.
AB  - The utility of the one-beam cross-correlation dynamic light-scattering system for
      sizing small particles in suspension was previously limited by its small
      intensity signal-to-baseline ratio for strongly turbid suspensions. We describe
      three improvements in the optical system and sample cell that raise the ratio to
      a value comparable with that of other cross-correlation dynamic light-scattering
      systems. These improvements are (i) using a square cross-sectional sample cell to
      minimize the attenuation of the incident beam and singly scattered light, (ii)
      placing a 200-microm-wide slit between the sample cell and the detector fibers to
      mask off the region of weak single scattering and strong multiple scattering from
      the detectors' field of view, and (iii) aligning the center of the detectors'
      field of view with the region of strongest single scattering. We analyze a number
      of suspensions of polystyrene latex spheres with a diameter between 65 and 562 nm
      in water using this improved one-beam instrument and find that the measured
      radius is determined in a 2-min data collection time to better than +/-10% for
      volume fractions of the suspended polystyrene latex spheres up to a few percent.

PMID- 18319940
TI  - Analysis of the instrumental line shape of high-resolution fourier transform IR
      spectrometers with gas cell measurements and new retrieval software.
AB  - The instrumental line shape (ILS) of two commercial high-resolution Fourier
      transform IR spectrometers has been analysed with gas cell measurements and a new
      ILS retrieval software LINEFIT. The instruments are used for atmospheric remote
      sounding, and the compatibility of the ILS deduced from laboratory gas cell
      measurements with the ILS in the atmospheric measurement itself is examined.

PMID- 18319941
TI  - Visible absorption bands of the (O2)2 collision complex at pressures below 760
      Torr.
AB  - The collision-induced absorption of oxygen in the 540-650-nm wavelength region
      has been measured ata pressure range from 0 to 730 Torr at T 5 294 K. Pressure
      dependent cross sections of the X 3Sigmag(+)+X 3Sigmag alpha 1Deltag(nu =0) +
      alpha 1Deltag(nu = 1 ) and X 3Simag(+)+ X 3Sigmag+--> alpha 1Deltag(nu =0) + 1
      alpha 1Deltag (nu = 0) transitions have been determined by means of cavity
      ringdown spectroscopy. Contributions of the overlapping g and d bands of O2 have
      been evaded, and Rayleigh extinction has been taken into account.

PMID- 18319943
TI  - Third-generation holographic Rowland mounting: fourth-order theory.
AB  - The third-generation holographic Rowland mount consists of a Rowland-mounted,
      optimally recorded holographic spherical grating, referred to as an optimized
      Rowland grating (ORG), whose recording sources are aberrated by two auxiliary
      ORG's. The main purpose of this mount is to avoid any aspherical surface while
      providing control over all the parameters needed to correct the aberrations up to
      and including the fourth order. Earlier [Appl. Opt. 30, 4019-4025 (1991)], we
      considered the case of a moderate coma c2. We now give the fourth-order theory,
      apply it to the high-dispersion (4600 grooves/mm) grating considered previously,
      and obtain for it diffraction-limited images.

PMID- 18319944
TI  - Dependence of fringe spacing on the grating separation in a long-period fiber
      grating pair.
AB  - The spectral spacing of the interference fringes formed by a pair of long-period
      fiber gratings was investigated. The variation of the fringe spacing was measured
      while the separation between the gratings was changed from 22 to 500 mm. When the
      grating separation was much longer than the length of the individual grating, the
      inverse of the fringe spacing became linearly proportional to the grating
      separation and to the differential effective group index of the fiber. In the
      third stop band of the grating pair, made along a dispersion-shifted fiber
      centered at 1.55 microm, the differential effective group index was calculated to
      be approximately 6.4 x 10(-3), which is approximately twice the differential
      effective index of the fiber. The discrepancy between the two indices was
      observed to decrease with the band order, a phenomenon that is explained by the
      first-order dispersion of the fiber. The measured interference fringes were not
      regularly spaced in the frequency domain, but regular spacing is required in
      wavelength-division multiplexing communication systems. Analysis of the second
      order dispersion of the fiber and the grating-induced nonlinear phase shift
      within grating regions as the factors that induce chirping on the fringe spacing
      is presented.

PMID- 18319945
TI  - Pulsed digital holography for high-speed contouring that uses a two-wavelength
      method.
AB  - A two-wavelength method for a fast shape measurement by use of a pulsed ruby
      laser is presented. The wavelength change is produced by alteration of the
      distance between the plates of the laser's output etalon. One plate of the etalon
      is mounted on a vibrating piezoelectric element; this allows a fast wavelength
      change. Two holograms at different wavelengths are recorded in a few microseconds
      by use of a CCD. The holograms are reconstructed digitally, and the wave-front
      phase is calculated. The shape is obtained by subtraction of the phases of the
      wave fronts recorded at different wavelengths. Environmental disturbances at low
      frequencies, such as air turbulence, vibrations, and object drift, have no
      influence on the measurement. Experimental results are presented.

PMID- 18319946
TI  - Measurement of three-dimensional temperature fields with interferometric
      tomography.
AB  - Optical computerized tomography (OCT) technology is used to reconstruct the
      asymmetric three-dimensional temperature field generated by radiators and
      electronic chips. First, the OCT method is described. Second, the reconstructed
      results are tested by a double-cylinder radiator model. Finally, OCT is applied
      to reconstruction of the temperature field above the surface of a CPU. The air
      temperature field above a CPU circuit can be imaged with an OCT system that
      reflects whether the heat production from different parts of the CPU is even;
      therefore possibly the technique can be used to determine whether the integrated
      circuit design in the CPU is smart.

PMID- 18319947
TI  - Digital speckle correlation method based on wavelet-packet noise-reduction
      processing.
AB  - Despite the advantages of being highly sensitive and nondestructive, the digital
      speckle correlation method (DSCM) may have difficulties in detecting tiny defects
      such as delaminations in multilayer ceramic capacitors. This is because the
      presence of background noise always complicates the data processing. We present a
      new algorithm, which employs the wavelet-packet noise-reduction process together
      with the improved DSCM, to improve data processing. Both the computational error
      and the noise are shown to be reduced successfully by this new algorithm. The
      accuracy (or precision) of the improved DSCM is increased after operation of the
      wavelet-packet noise-reduction process. The most important feature of this new
      algorithm is that it can extract a small hillock signal from a large noisy
      background in a DSCM deformation result. This helps to save time in the detection
      of tiny defects, such as delamination, in a miniaturized electronic component.

PMID- 18319948
TI  - Aberration extraction in the hartmann test by use of spatial filters.
AB  - Using a computer, we generated a set of filters to aid in the retrieval of
      aberration functions from Hartmanngrams. These filters consist of discrete two
      dimensional data points, like the Hartmanngrams themselves, and are
      orthogonalized by the Gram-Schmidt procedure. The aberration coefficients are
      obtained by calculation of the scalar product of the Hartmanngram and each
      orthogonal filter.

PMID- 18319949
TI  - General and self-consistent method for the calibration of polarization
      modulators, polarimeters, and mueller-matrix ellipsometers.
AB  - Calibration of polarization-state generators (PSG's), polarimeters, and Mueller
      matrix ellipsometers (MME's) is an important factor in the practical use of these
      instruments. A new general procedure, the eigenvalue calibration method (ECM), is
      presented. It can calibrate any complete MME consisting of a PSG and a
      polarimeter that generate and measure, respectively, all the states of
      polarization of light. In the ECM, the PSG and the polarimeter are described by
      two 4 x 4 matrices W and A, and their 32 coefficients are determined from three
      or four measurements performed on reference samples. Those references are smooth
      isotropic samples and perfect linear polarizers. Their optical characteristics
      are unambiguously determined during the calibration from the eigenvalues of the
      measured matrices. The ECM does not require accurate alignment of the various
      optical elements and does not involve any first-order approximation. The ECM also
      displays an efficient error control capability that can be used to improve the
      MME behavior. The ECM is illustrated by an experimental calibration, at two
      wavelengths (458 and 633 nm), of a MME consisting of a coupled phase modulator
      associated with a prism division-of-amplitude polarimeter.

PMID- 18319950
TI  - Improvement of measurement accuracy in shadow moire by considering the influence
      of harmonics in the moire profile.
AB  - A method for high-resolution three-dimensional shape measurement for a shadow
      moire system is proposed. To increase the resolving power of the method, the
      problem caused by the harmonics of the moire profile needs to be solved. It is
      well known that moire fringes in a shadow moire system have a nonsinusoidal
      profile caused by harmonics. The influence of the harmonics in moire profile on
      the measurement accuracy of the method is discussed. The method is improved to
      eliminate the error caused by the harmonics in the moire profile. Both simulation
      and experimental results show that the improved method can effectively reduce the
      influence of harmonics.

PMID- 18319951
TI  - Three-dimensional phase imaging with a scanning optical-fiber interferometer.
AB  - We describe a quantitative method for measuring the phase of a propagating wave
      field in three dimensions by use of a scanning optical-fiber interferometer.
      Because phase modulation in the reference arm is exploited, this technique is
      insensitive to large variations in the intensity of the field being studied and
      is therefore highly suitable for measurement of phase within spatially confined
      optical beams. It uses only a single detector and is not reliant on lock-in
      electronics. The technique is applied to the measurement of the near field of a
      cleaved optical fiber and is shown to produce results in good agreement with
      theory.

PMID- 18319952
TI  - Ultraviolet interferometry with apochromatic reflection optics.
AB  - To improve the resolution and the sensitivity of optical metrology, we have
      constructed an interferometer for vacuum-ultraviolet wavelengths. To examine the
      influence of the wavelength, especially with regard to the period of the object's
      structure, we chose an apochromatic design. With reflective optics, wavelengths
      from 157 to 900 nm can be employed for interferometric measurements. The benefits
      and also the technological problems that accompany the use of vacuum-ultraviolet
      wavelengths are discussed. The design of this interferometer and measuring
      results with different wavelengths are presented.

PMID- 18319953
TI  - Dual-domain point diffraction interferometer.
AB  - The phase-shifting point diffraction interferometer has recently been developed
      and implemented at Lawrence Berkeley National Laboratory to meet the significant
      metrology challenge of characterizing extreme ultraviolet projection lithography
      systems. Here we present a refined version of this interferometer that overcomes
      the original design's susceptibility to noise attributed to scattered light. The
      theory of the new hybrid spatial- and temporal-domain (dual-domain) point
      diffraction interferometer is described in detail and experimental results are
      presented.

PMID- 18319954
TI  - Spatiotemporal phase unwrapping for the measurement of discontinuous objects in
      dynamic fringe-projection phase-shifting profilometry.
AB  - A spatiotemporal phase-unwrapping method is presented that combines the dynamic
      fringe-projection method and the phase-shifting technique and extends the phase
      unwrapping method, which measures two phase maps at different sensitivities. The
      most important feature of the method is that it makes possible the automatic
      three-dimensional shape measurement of discontinuous objects with large dynamic
      range limits and high precision because the effective wavelength of the fringe
      projection profilometry can be continuously varied over several orders of
      magnitude by rotation of the projection grating in its own plane. Only one
      grating and several steps of rotating the grating are required; therefore the
      method is inherently simple, fast, and robust. In the experiment, choosing the
      rotation angle was crucial for optimizing the measurement speed and the
      measurement accuracy. A criterion is presented for the choice of the minimum
      number of rotational steps for a given accuracy. The experimental results
      demonstrate the validity of the proposed method.

PMID- 18319955
TI  - Focal-length measurement by multiple-beam shearing interferometry.
AB  - The application of multiple-beam shearing interferometry to lens focal-length
      measurement is described. A coated shearing plate interferometer was used in
      transmission to produce sharp multiple-beam fringes that rotate as the
      collimation of the incoming wave front from the lens under test changes. The test
      lens was used to collimate light from a point source that was translated
      longitudinally, and the focal length was determined from the rate of rotation of
      the fringes as the source moved. This method is simple, accurate, and lends
      itself to automatic determination of focal length.

PMID- 18319956
TI  - Phase-step calibration for phase-stepped interferometry.
AB  - A novel method to set the proper phase steps, as used in phase-stepped
      interferometry, is presented. It is indicated how and when this method can be
      used. With only two images one can deduce the relative phase step between them by
      calculating the correlation between the two images. The error of the proposed
      method is shown to be smaller than 0.1%.

PMID- 18319957
TI  - Unified calibration technique and its applications in optical triangular
      profilometry.
AB  - A unified calibration technique based on ray tracing for optical triangular
      profilometry is presented. The proposed technique based on the inherent geometric
      relation between depth and a distorted signal is capable of speedy and accurate
      measurement without the determination of geometric parameters. The technique can
      also reduce calibration error caused by the lens distortion of the projector and
      the camera owing to the reasonable assumption that mapping in a small local area
      is a linear transformation and the coefficients of the linear transformation may
      be varied in different local areas. Three classical systems of triangular
      profilometry, spot inspection, a single-line system, and a projection-grating
      system, are discussed and demonstrated by experiment.

PMID- 18319958
TI  - Effect of a finite-size pinhole on noise performance in single-, two-, and three
      photon confocal fluorescence microscopy.
AB  - It is known that signal level in single-, two- and three-photon confocal
      fluorescence microscopy increases with the size of the detector. Here we evaluate
      the signal-to-noise and the signal-to-background criteria for these microscopes.
      We investigate the effect of pinhole size on their ability to detect a weakly
      fluorescent point object in the presence of a uniformly fluorescence background.
      Numerical results based on a paraxial approximation theory show that optimization
      of these criteria gives an optimal value for pinhole size, which results in an
      improved imaging performance. The resulting improvement in noise performance,
      compared with the use of a large detector, is greater for three-photon than for
      two-photon confocal fluorescence microscopes.

PMID- 18319959
TI  - Silicon planar-apertured probe array for high-density near-field optical storage.
AB  - We propose a novel, to our knowledge, silicon planar-apertured probe array as an
      optical head for high-density near-field optical storage. In comparison with a
      conventional fiber probe employed for near-field optical storage the apertured
      probe array has a higher readout data-transmission rate and better mechanical
      durability. A probe array with an aperture size of 100 nm was fabricated by use
      of photolithography and wet etching of a silicon wafer. Subwavelength-readout
      capability was demonstrated by use of one aperture of the probe array.
      Furthermore, we achieved a 16 times increase in the light-transmission efficiency
      of the probe array by installing glass-sphere microlenses on each aperture. The
      increase was confirmed by measurement of the near-field optical intensity.

PMID- 18319960
TI  - Photographic optical systems with nonrotational aspheric surfaces.
AB  - Sections of nonrotational aspheric surfaces can be useful in a variety of optical
      situations. In several examples, image-forming objectives, as for photographic or
      electronic camera products, are described in which suitably located asymmetric
      pairs of refractive surfaces are devised, such that relative rotation about a
      displaced axis of one with respect to the other can be used to produce a focusing
      effect that is satisfactory for imaging purposes over reasonable fields of view
      and for practicable apertures and achromatic corrections. Taylor expansions about
      assignable reference points in any given surface of a sequence, together with
      suitable coordinate systems, can be employed to relate performance to shape
      parameters.

PMID- 18319961
TI  - Concentration of diffuse linear light sources with continuous optical elements.
AB  - A new technique for geometric transformation of a diffuse linear light source
      into a two-dimensional symmetric virtual source is proposed and demonstrated. It
      involves two cylindrical lenses and a single holographic element that is
      optically recorded with a simple and single step. The results for a specific
      arrangement that transforms a 40 mm x 0.4 mm source, with diffusive angle of 0.1
      rad, into a 1 mm x 1.2 mm nearly symmetric spot are presented. The lack of sharp
      boundaries in either the beam or the optical elements suppresses any diffraction
      losses, relaxes alignment tolerances, and improves stability.

PMID- 18319962
TI  - Linear cylindrical taper as optical line source.
AB  - We propose to use a linear cylindrical taper as an optical line illuminator for
      various light-emitting-diode-based emerging scanning and display applications. A
      simple model to explain the mechanism of this line illuminator is presented.
      Experimental verifications are performed, and main performance characteristics
      are discussed.

PMID- 18319963
TI  - Light emission from sources located within metallodielectric planar
      microcavities.
AB  - A simple, rigorous electromagnetic formula is derived for predicting the
      electromagnetic power provided by sources located in transparent or dissipative
      planar microcavities. With this simple approach, we compare numerically and
      experimentally the electromagnetic power that escapes the microcavity when the
      source is located in a metallodielectric or in an all-dielectric resonant planar
      structure. Although a strong light-extraction coefficient might be expected for
      metallodielectric microcavities, we show that these attractive structures suffer
      from metal absorption even when thin metallic layers are used. Experiments
      implemented with europium chelates located in metallodielectric or in all
      dielectric microcavities confirm this result.

PMID- 18319964
TI  - Ion-assisted deposition of oxide materials at room temperature by use of
      different ion sources.
AB  - Thin films of SiO(2), TiO(2), Ta(2)O(5), ZrO(2), and the mixed oxide H4 (Merck)
      have been deposited onto nonheated glass substrates by electron-beam evaporation
      in commercial coating plants. All depositions have been carried out with ion
      assistance provided by three different ion or plasma sources (end-hall, plasma,
      and cold-cathode sources). The optical film properties such as index of
      refraction, extinction coefficient, light scattering, and absorption have been
      examined by spectrophotometry, laser calorimetry, and total integrated light
      scatter measurements. Surface morphology has been investigated by atomic force
      microscopy studies. Furthermore, films have undergone sand erosion tests for the
      determination of relative wear resistance. The film properties are compared for
      the three different ion sources.

PMID- 18319965
TI  - Measurement of the electron-phonon coupling factor dependence on film thickness
      and grain size in Au, Cr, and Al.
AB  - Femtosecond thermoreflectance data for thin films and bulk quantities of Au, Cr,
      and Al are compared with the parabolic two-step thermal diffusion model for the
      purpose of determining the electron-phonon coupling factor. The thin films were
      evaporated and sputtered onto different substrates to produce films that vary
      structurally. The measurement of the electron-phonon coupling factor is shown to
      be sensitive to grain size and film thickness. The thin-film thermoreflectance
      data are compared with that of the corresponding bulk material and to a
      theoretical model relating the coupling rate to the grain-boundary scattering and
      size effects on the mean free path of the relevant energy carrier.

PMID- 18319966
TI  - Serial bideposition of anisotropic thin films with enhanced linear birefringence.
AB  - We describe a serial bideposition technique in which a tilted substrate is
      rotated stepwise by half a turn about a normal axis during the evaporation of a
      metal oxide from a single electron-beam source. Coatings formed by the new method
      develop a columnar nanostructure that is perpendicular to the substrate and has
      greatest width or bunching perpendicular to the common deposition plane. With
      appropriate choice of deposition parameters, the method produces biaxial films
      with large birefringence, principal axes aligned parallel and perpendicular to
      the substrate, and improved uniformity. Measured phase retardances for light
      incident normally on the films are double the corresponding values for tilted
      columnar films.

PMID- 18319967
TI  - Fourier analysis of light scattered by elongated scatterers.
AB  - Biological stimulation of living cells is sometimes associated with morphological
      changes. A practical method is developed to monitor cell stimulation by means of
      their conformational changes through interpretation of the pattern of light
      scattered from a cell population. For this purpose a mathematical model is
      suggested that predicts the power spectrum from a population of elliptic objects
      with a given eccentricity. A computer simulation of that model is presented
      together with supporting experimental results of the simulation. The predicted
      and the measured spectra are in good agreement. This technique was applied to
      elongated cells that become circular on exposure to a human hormone, indicating
      the potential applicability of the method in biology and medicine. The method and
      the apparatus presented in this study could be applied to bioassays of cell
      systems that respond to a variety of stimulants and to trace quantitatively the
      structural changes that occur during biological processes.

PMID- 18319968
TI  - Influence of optical aberrations on laser-induced plasma formation in water and
      their consequences for intraocular photodisruption.
AB  - The influence of spherical aberrations on laser-induced plasma formation in water
      by 6-ns Nd:YAG laser pulses was investigated for focusing angles that are used in
      intraocular microsurgery. Waveform distortions of 5.5lambda and 18.5lambda
      between the optical axis and the 1/e(2) irradiance values of the laser beam were
      introduced by replacement of laser achromats in the delivery system by
      planoconvex lenses. Aberrations of 18.5lambda increased the energy threshold for
      plasma formation by a factor of 8.5 compared with the optimized system. The
      actual irradiance threshold for optical breakdown was determined from the
      threshold energy in the optimized system and the spot size measured with a knife
      edge technique. For aberrations of 18.5lambda the irradiance threshold was 48
      times larger than the actual threshold when it was calculated by use of the
      diffraction-limited spot size but was 35 times smaller when it was calculated by
      use of the measured spot size. The latter discrepancy is probably due to hot
      spots in the focal region of the aberrated laser beam. Hence the determination of
      the optical-breakdown threshold in the presence of aberrations leads to highly
      erroneous results. In the presence of aberrations the plasmas are as much as 3
      times longer and the transmitted energy is 17-20 times higher than without
      aberrations. Aberrations can thus strongly compromise the precision and the
      safety of intraocular microsurgery. They can further account for a major part of
      the differences in the breakdown-threshold and the plasma-transmission values
      reported in previous investigations.

PMID- 18319969
TI  - Estimation of transmittance spectra from multiband micrographs of fungi and its
      application to segmentation of conidia and hyphae.
AB  - Transmittance spectra of fungi were estimated from seven-band optical
      micrographs. An optical microscope adjusted with a single-chip CCD camera with
      seven band filters was used for image acquisition. The Wiener method was applied
      to estimate the transmittance spectra of five species that belong to one genus of
      fungi. The Wiener estimation operator was calculated from transmittance spectra
      of 16 color transparencies and the corresponding camera responses. The estimated
      transmittance spectra were used for segmentation of conidia and hyphae in fungal
      optical micrographs; then the competitive learning in an artificial neural
      network was applied to the segmentation.

PMID- 18319970
TI  - Light scattering from cells: finite-difference time-domain simulations and
      goniometric measurements.
AB  - We have examined the light-scattering properties of inhomogeneous biological
      cells through a combination of theoretical simulations and goniometric
      measurements. A finite-difference time-domain (FDTD) technique was used to
      compute intensity as a function of scattering angle for cells containing multiple
      organelles and spatially varying index of refraction profiles. An automated
      goniometer was constructed to measure the scattering properties of dilute cell
      suspensions. Measurements compared favorably with FDTD predictions. FDTD and
      experimental results indicate that scattering properties are strongly influenced
      by cellular biochemical and morphological structure.

PMID- 18319971
TI  - Fluorescence measurement in thick tissue layers by linear or nonlinear long
      wavelength excitation.
AB  - Samples of different animal tissues containing, at variable depth, a thin
      fluorescent sheet are irradiated with continuous violet or red light or with
      nonlinearly absorbed pulsed infrared light. The fluorescence intensity measured
      at the tissue surface as a function of the location of the fluorescent sheet
      exhibits, after a transition zone close to the tissue surface, an exponential
      decrease, the slope of which depends on the optical penetration depths of the
      exciting and the fluorescent light. From these results the total fluorescence
      output is determined for specific fluorophor distributions. It is seen that
      considerably deeper tissue layers are explored by use of excitation with red
      instead of violet light. Nonlinear excitation by infrared light can provide a
      further improvement, especially in liver tissue.

PMID- 18319972
TI  - Compact tissue oximeter based on dual-wavelength multichannel time-resolved
      reflectance.
AB  - We developed a compact dual-wavelength multichannel tissue oximeter based on the
      time-correlated single-photon counting (TCSPC) technique. The light sources are
      two pulsed diode lasers (output wavelengths of 672 and 818 nm, an average power
      of 1 mW, a pulse duration of 100 ps, and a pulse-repetition rate as high as 80
      MHz). The time-resolved reflectance photons are detected by a multianode
      photomultiplier, and the output signals are redirected by a router to different
      memory blocks of the TCSPC personal computer board. The system's accuracy in
      determining the absorption microa and the reduced-scattering micros' coefficients
      and in reconstructing absorber concentrations in diffusive media was tested on
      phantoms. Preliminary in vivo tissue-oxygenation measurements were performed on
      healthy volunteers under different physiological conditions with a minimum
      acquisition time of 100 ms and an injected power of less than 100 microW.

PMID- 18319973
TI  - Time-resolved transmission through homogeneous scattering media: time-response
      effects.
AB  - An analytical expression has been obtained that describes the time variation of
      time-resolved signals transmitted through or reflected by a homogeneous
      scattering slab as measured with a detection system having a square-impulse
      response. This expression can be used to improve the match between theoretical
      and experimental time-resolved signals measured with a system having a finite
      response time. It can also be used to assess the effect of a finite detection
      response time on the time-domain characterization of a turbid medium. The
      expression can be adapted to detection systems that are not time invariant.

PMID- 18319974
TI  - Time-domain optical imaging: discrimination between scattering and absorption.
AB  - A technique for discriminating between scattering and absorbing inclusions
      located in the center of a scattering slab is presented. The technique is based
      on an empirical model that provides a simple mathematical expression to describe
      the change in the time-resolved transmission resulting from the presence of an
      inclusion. Experimental results from various configurations show that the
      technique allows for proper recognition of the type of an inclusion whether it is
      scattering or absorbing. This technique is a significant step toward tissue
      differentiation.

PMID- 18319975
TI  - Time-alternating method based on single-sideband holography with half-zone-plate
      processing for the enlargement of viewing zones.
AB  - The single-sideband method of holography, as is well known, cuts off beams that
      come from conjugate images for holograms produced in the Fraunhofer region and
      from objects with no phase components. The single-sideband method with half-zone
      plate processing is also effective in the Fresnel region for beams from an object
      that has phase components. However, this method restricts the viewing zone to a
      narrow range. We propose a method to improve this restriction by time-alternating
      switching of hologram patterns and a spatial filter set on the focal plane of a
      reconstruction lens.

PMID- 18319976
TI  - Narrow-band resonant grating waveguide filters constructed with azobenzene
      polymers.
AB  - Resonant grating waveguide structures were used to fabricate narrow-bandwidth
      optical filters. Azopolymer films were deposited on top of slab waveguides, and
      surface relief gratings were optically inscribed on them to be used as couplers.
      This technique is a simple one-step process and produces efficient gratings with
      high accuracy. Sharp resonant peaks are observed in the transmission and the
      reflection spectra of these structures. The thickness and the index of refraction
      of the waveguide can be accurately determined from these resonances by use of
      modal theory. These parameters are then used in the design of an optical filter.
      Bandwidths of less than 1 nm and a decrease in transmitted signal of 60% are
      reported. Measurement of these values was limited by the divergence of the probe
      beam.

PMID- 18319977
TI  - Optical symmetry filtering by use of anisotropic self-diffraction in BaTiO3
      crystals.
AB  - We propose what we believe to be a novel and simple method for optical symmetry
      filtering, using anisotropic self-diffraction in BaTiO(3) crystals. This method
      allows us to distinguish a centrosymmetric pattern from a noncentrosymmetric
      pattern easily with scale invariance. It is self-referential; no extra reference
      element is required. Both the theory and the experiment are demonstrated.

PMID- 18319978
TI  - Rainbow holography with large image depth.
AB  - A synthetic slit method is used to record the rainbow hologram of a three
      dimensional diffused object directly, without any lens. By controlling the
      position of the synthetic slit, we use this method to produce the reconstructed
      image of a hologram with much larger image depth than without such control.

PMID- 18319979
TI  - Hologram reconstruction by use of optical wavelet transform.
AB  - High-speed in-line holography is used to visualize the trajectories of glass
      fibers being drawn out in a turbulent flame. To improve the signal-to-noise
      ratio, the images are not observed by a conventional reconstruction setup, but
      the holographic plate is placed directly on the input plane of a wavelet
      transform optical system. This processing system is based on a VanderLugt
      correlator with inclusion of an electrically addressed spatial light modulator.
      The shape of the matched filters is deduced by successive rotation and dilatation
      operations of wavelet functions in the Fourier domain. We estimate the three
      dimensional location of a fiber element and its orientation by searching for the
      daughter wavelet that yields the maximum intensity on the output plane of the
      correlator, which also contains the reconstructed image. The results are compared
      with those obtained by conventional optical reconstruction. The signal-to-noise
      ratios of the images observed on the output plane are improved. Moreover, it is
      shown that the axis coordinate accuracy is improved to Dz = +/-50 microm, instead
      of +/-0.5 mm for holographic reconstruction.

PMID- 18319980
TI  - Image compression by vector quantization with noniterative derivation of a
      codebook: applications to video and confocal images.
AB  - We demonstrate an image-compression technique that uses what we believe is a new
      noniterative codebook generation algorithm for vector quantization. The technique
      supports rapid decompression and is equally applicable to individual images or to
      a set of images without the need for interframe processing. Compression with a
      single-image codebook is tested on (1) ten confocal images of the hindbrain of a
      mouse embryo, (2) video images of a polystyrene microsphere that is manipulated
      by a focused laser light, and (3) five fluorescence images of the embryo eye lens
      taken at different magnifications. The reconstructions are assessed with the
      normalized mean-squared error and with Linfoot's criteria of fidelity, structural
      content, and correlation quality. Experimental results with single-image
      compression show that the technique produces fewer local artifacts than JPEG
      compression, especially with noisy images. Results with video and confocal image
      series indicate that single-image codebook generation is sufficient at practical
      compression ratios for producing acceptable reconstructions for mouse embryo
      analysis and for viewing optically trapped microspheres. Experiments with the
      magnified images also reveal that the compression scheme is robust to scaling.

PMID- 18319981
TI  - Mixed-expectation image-reconstruction technique.
AB  - An iterative method of reconstructing degraded images is developed from
      consideration of a mixed-noise imaging situation. Both photon noise in the image
      itself and postdetection Gaussian noise are combined by use of the standard
      maximum-likelihood method to produce a mixed-expectation reconstruction technique
      that demonstrates good performance in the presence of both noise sources. The new
      algorithm is evaluated through computer simulations.

PMID- 18319982
TI  - Polarization microscopy of magnetic domains for magneto-optical disks.
AB  - Polarization microscopes are widely used to image the magnetic domains of a
      magneto-optical disk and to characterize the birefringence of the disk substrate.
      For high-resolution imaging, unfortunately, the coupling of the polarization
      rotation from the Kerr signal, the effect of Fresnel's reflection coefficients,
      and the substrate birefringence severely deteriorate the image contrast obtained
      from conventional observations. Here we present the technique of differential
      polarization microscopy, which replaces the analyzer with a Wollaston prism, for
      providing better image contrast. Images of a magnetic pattern obtained with both
      conventional and differential methods are observed for objective lenses that have
      different numerical apertures and magneto-optical disks with and without a
      birefringent substrate. The computer simulations and experimental results show
      that the use of this differential method improves the image contrast and provides
      excellent tolerance for defects of the optical system.

PMID- 18319983
TI  - Neural network pattern recognition by means of differential absorption Mueller
      matrix spectroscopy.
AB  - Artificial neural network systems were built for detecting amino acids, sugars,
      and other solid organic matter by pattern recognition of their polarized light
      scattering signatures in the form of a Mueller matrix. Backward-error propagation
      and adaptive gradient descent methods perform network training. The product of
      the training is a weight matrix that, when applied as a filter, discerns the
      presence of the analytes on the basis of their cued susceptive Mueller matrix
      difference elements. This filter function can be implemented as a software or a
      hardware module to a future differential absorption Mueller matrix spectrometer.

PMID- 18319984
TI  - Quantitative study of the gray-scale fidelity of volume holographic images.
AB  - The reconstruction fidelity of gray-scale holographic images is analyzed
      quantitatively and assessed by use of proposed quantities, especially the
      correlation coefficient between the original and the retrieved images. The
      physical factors affecting the fidelity of photorefractive holograms are
      investigated experimentally, leading to results that are useful for the
      determination of the recording-beam ratio and the exposure dosage for high
      fidelity retrieval. Investigation of the effects of noise on the fidelity of
      multiplexed holograms suggests that, if multiple-gray-scale data pages are
      multiplexed in a given volume, the total bit capacity may be competitive with
      that realized by means of storing binary pages.

PMID- 18319985
TI  - Dual-wavelength optical head with a wavelength-selective filter for 0.6- and 1.2
      mm-thick-substrate optical disks.
AB  - A dual-wavelength optical head, believed to be new in design, for 0.6- and 1.2-mm
      thick-substrate optical disks was developed by use of 650- and 780-nm-wavelength
      light and a wavelength-selective filter, which reduces the spherical aberration
      that is due to the difference in substrate thicknesses and restricts the
      numerical aperture for 780-nm-wavelength light. According to this configuration,
      both high light power efficiency and wide image field characteristics are
      obtained, which are suitable not only for read-only but also for recordable or
      rewritable optical disk systems. A reading operation for a digital video disc and
      for a compact disc and a recording operation for a phase change optical disk were
      successfully demonstrated.

PMID- 18319986
TI  - Vector diffraction from subwavelength optical disk structures: two-dimensional
      modeling of near-field profiles, far-field intensities, and detector signals from
      a DVD.
AB  - Rigorous two-dimensional vector-diffraction patterns of a focused beam incident
      on an optical disk, specifically, a digital versatile disk (DVD), are examined
      both in the near field and in the far field. An efficient finite-difference
      frequency-domain method is developed for calculating the electromagnetic fields
      in the neighborhood of subwavelength dielectric and metallic structures. The
      results of vector-diffraction theory are compared with those of scalar
      diffraction theory for pressed DVD features that consist of pits or of bumps. The
      sum (data) and difference (tracking) signals from a split photodetector are also
      calculated for different disk features and for different polarizations. The
      subwavelength features of a DVD result in considerable vector-diffraction effects
      both in the near-field profiles and in the detector signals, depending not only
      on the polarization of illumination but also on whether the features are pits or
      bumps. This paper provides important insight into the vector-diffraction effects
      encountered in high-density optical data storage systems.

PMID- 18319987
TI  - Deformed-helix ferroelectric liquid-crystal spatial light modulator that
      demonstrates high diffraction efficiency and 370-line pairs/mm resolution.
AB  - New liquid-crystal media and photoconductor materials are being utilized in
      spatial light modulators to increase their resolution, diffraction efficiency,
      speed, and sensitivity. A prototypical device developed for real-time holography
      applications has shown an 8% diffraction efficiency from a holographic grating
      with a spatial frequency of 370 line pairs/mm (lp/mm). At 18 lp/mm the device has
      demonstrated a 31% diffraction efficiency with a 600-micros hologram write time
      using 400-nJ/cm(2) write beams.

PMID- 18319988
TI  - Pseudorandom encoding for real-valued ternary spatial light modulators.
AB  - Pseudorandom encoding with quantized real modulation values encodes only
      continuous real-valued functions. However, an arbitrary complex value can be
      represented if the desired value is first mapped to the closest real value
      realized by use of pseudorandom encoding. Examples of encoding real- and complex
      valued functions illustrate performance improvements over conventional minimum
      distance mapping methods in reducing peak sidelobes and in improving the
      uniformity of spot arrays.

PMID- 18319989
TI  - Femtosecond single-shot correlation system: a time-domain approach.
AB  - We introduce, analyze, and experimentally demonstrate what to the best of our
      knowledge is a new pulse correlation technique that is capable of real-time
      conversion of a femtosecond pulse sequence into its spatial image. Our technique
      uses a grating at the entrance of the system, thus introducing a transverse time
      delay (TTD) into the transform-limited reference pulse. The shaped signal pulses
      and the TTD reference pulse are mixed in a nonlinear optical crystal
      (LiB(3)O(5)), thus producing a second-harmonic field that carries the spatial
      image of the temporal shaped signal pulse. We show that the time scaling of the
      system is set by the magnification of the anamorphic imaging system as well as by
      the grating frequency and that the time window of the system is set by the size
      of the grating aperture. Our experimental results show a time window of
      approximately 20 ps. We also show that the chirp information of the shaped pulse
      can be recovered by measurement of the spectrum of the resulting second-harmonic
      field.

PMID- 18319990
TI  - Hyperspectral remote sensing for shallow waters. 2. Deriving bottom depths and
      water properties by optimization.
AB  - In earlier studies of passive remote sensing of shallow-water bathymetry, bottom
      depths were usually derived by empirical regression. This approach provides rapid
      data processing, but it requires knowledge of a few true depths for the
      regression parameters to be determined, and it cannot reveal in-water
      constituents. In this study a newly developed hyperspectral, remote-sensing
      reflectance model for shallow water is applied to data from computer simulations
      and field measurements. In the process, a remote-sensing reflectance spectrum is
      modeled by a set of values of absorption, backscattering, bottom albedo, and
      bottom depth; then it is compared with the spectrum from measurements. The
      difference between the two spectral curves is minimized by adjusting the model
      values in a predictor-corrector scheme. No information in addition to the
      measured reflectance is required. When the difference reaches a minimum, or the
      set of variables is optimized, absorption coefficients and bottom depths along
      with other properties are derived simultaneously. For computer-simulated data at
      a wind speed of 5 m/s the retrieval error was 5.3% for depths ranging from 2.0 to
      20.0 m and 7.0% for total absorption coefficients at 440 nm ranging from 0.04 to
      0.24 m(-1). At a wind speed of 10 m/s the errors were 5.1% for depth and 6.3% for
      total absorption at 440 nm. For field data with depths ranging from 0.8 to 25.0 m
      the difference was 10.9% (R2 = 0.96, N = 37) between inversion-derived and field
      measured depth values and just 8.1% (N = 33) for depths greater than 2.0 m. These
      results suggest that the model and the method used in this study, which do not
      require in situ calibration measurements, perform very well in retrieving in
      water optical properties and bottom depths from above-surface hyperspectral
      measurements.

PMID- 18319991
TI  - Reduction of skylight reflection effects in the above-water measurement of
      diffuse marine reflectance.
AB  - Reflected skylight in above-water measurements of diffuse marine reflectance can
      be reduced substantially by viewing the surface through an analyzer transmitting
      the vertically polarized component of incident radiance. For maximum reduction of
      effects, radiometric measurements should be made at a viewing zenith angle of
      approximately 45 degrees (near the Brewster angle) and a relative azimuth angle
      between solar and viewing directions greater than 90 degrees (backscattering),
      preferably 135 degrees. In this case the residual reflected skylight in the
      polarized signal exhibits minimum sensitivity to the sea state and can be
      corrected to within a few 10(-4) in reflectance units. For most oceanic waters
      the resulting relative error on the diffuse marine reflectance in the blue and
      green is less than 1%. Since the water body polarizes incident skylight, the
      measured polarized reflectance differs from the total reflectance. The
      difference, however, is small for the considered geometry. Measurements made at
      the Scripps Institution of Oceanography pier in La Jolla, Calif., with a
      specifically designed scanning polarization radiometer, confirm the theoretical
      findings and demonstrate the usefulness of polarization radiometry for measuring
      diffuse marine reflectance.

PMID- 18319992
TI  - Modeling the combined effect of static and varying phase distortions on the
      performance of adaptive optical systems.
AB  - The end-to-end performance achieved by an adaptive optical (AO) imaging system is
      determined by a combination of the residual time-varying phase distortions
      associated with atmospheric turbulence and the quasi-static unsensed and
      uncorrectable aberrations in the optical system itself. Although the effects of
      these two errors on the time-averaged Strehl ratio and the time-averaged optical
      transfer function (OTF) of the AO system are not formally separable, such an
      approximation is found to be accurate to within a few percent for a range of
      representative residual wave-front errors. In these calculations, we combined
      static optical system aberrations and time-varying residual phase distortion
      characteristics of a deformable mirror fitting error, wave-front sensor noise,
      and anisoplanatism. The static aberrations consist of focus errors of varying
      magnitudes as well as a combination of unsensed and uncorrectable mirror figure
      errors derived from modeling by the Gemini 8-Meter Telescopes Project. The
      overall Strehl ratios and OTF's that are due to the combined effect of these
      error sources are well approximated as products of separate factors for the
      static and time-varying aberrations, as long as the overall Strehl ratio that is
      due to both errors is greater than approximately 0.1. For lower Strehl ratios,
      the products provide lower bounds on the actual values of the Strehl ratio and
      the OTF. The speckle transfer function is also well approximated by a product of
      two functions, but only where AO compensation is sufficiently good that speckle
      imaging techniques are usually not required.

PMID- 18319993
TI  - Method to determine snow albedo values in the ultraviolet for radiative transfer
      modeling.
AB  - For many cases modeled and measured UV global irradiances agree to within +/-5%
      for cloudless conditions, provided that all relevant parameters for describing
      the atmosphere and the surface are well known. However, for conditions with snow
      covered surfaces this agreement is usually not achievable, because on the one
      hand the regional albedo, which has to be used in a model, is only rarely
      available and on the other hand UV irradiance alters with different snow cover of
      the surface by as much as 50%. Therefore a method is given to determine the
      regional albedo values for conditions with snow cover by use of a
      parameterization on the basis of snow depth and snow age, routinely monitored by
      the weather services. An algorithm is evolved by multiple linear regression
      between the snow data and snow-albedo values in the UV, which are determined from
      a best fit of modeled and measured UV irradiances for an alpine site in Europe.
      The resulting regional albedo values in the case of snow are in the 0.18-0.5
      range. Since the constants of the regression depend on the area conditions, they
      have to be adapted if the method is applied for other sites. Using the algorithm
      for actual cases with different snow conditions improves the accuracy of modeled
      UV irradiances considerably. Compared with the use of an average, constant snow
      albedo, the use of actual albedo values, provided by the algorithm, halves the
      average deviations between measured and modeled UV global irradiances.

PMID- 18319994
TI  - Partitioning in situ total spectral absorption by use of moored spectral
      absorption-attenuation meters.
AB  - High-temporal-resolution spectral absorption data were acquired by use of one
      bottom-mounted (approximately 68-m) and three moored spectral absorption and
      attenuation meters (ac-9 meters at 14, 37, and 52 m) on the Middle Atlantic Bight
      continental shelf during the fall 1996 period of the Coastal Mixing and Optics
      experiment. We employed a previously published spectral absorption model with the
      data to partition total absorption into absorption by water, phytoplankton,
      detritus, and gelbstoff (dissolved matter). We validated the model by comparing
      its results against coincident in vivo absorption coefficients derived from
      discrete bottle samples. Correlations between modeled and in vivo spectra range
      from 0.873 to 0.998. We optimized these correlations to determine the model
      parameters. These parameters could not be determined solely from the moored ac-9
      results. Therefore a separate set of absorption measurements (from discrete
      bottle samples) was necessary to permit values for the model parameters to be
      determined. Model results allow us to separate particulate and dissolved
      components of absorption and to examine the temporal variability and the vertical
      distributions and concentrations of each component, given the total absorption in
      the water column.

PMID- 18319995
TI  - Transmission of linearly polarized light through a single-mode fiber with random
      fluctuations of birefringence.
AB  - A simple theoretical formalism is developed to describe the effect of
      transmission on linearly polarized light through a fiber with random fluctuations
      of birefringence. We conclude that, for any optical fiber that does not
      experience polarization-dependent gain or loss, there exist two orientations for
      linearly polarized light input into the optical fiber that will also exit the
      fiber linearly polarized. We report experimental results that verify this
      prediction and also investigate its practical implications and limitations; in
      particular we investigate the stability of these linearly polarized output states
      in laboratory conditions.

PMID- 18319996
TI  - Photobleaching for optical waveguide formation in a guest-host polyimide.
AB  - We present a methodology for determining the bleaching characteristics of dye
      doped polymers. Our general phenomenological model predicts the absorption
      spectrum as well as the change in index of refraction as a function of wavelength
      for a bleached film. Determination of the parameters of the model requires only
      measurements of physical film characteristics (e.g., thickness, dye
      concentration), absorption features, and one index of refraction point. Our
      technique requires no detailed knowledge of the chemistry or physics of the
      polymer dye system. We have demonstrated the efficacy of our methodology by
      characterizing a guest-host system of 4-dicyanomethylene-2-methyl-6-(p
      dimethylaminostyryl)-4-H-pyran in Amoco 4212 polyimide. Based on our results, we
      speculate that it should be straightforward to generate model parameter values to
      characterize the bleaching of other dye-doped polymer systems.

PMID- 18319997
TI  - Theory for a new full-vectorial beam-propagation method in anisotropic
      structures.
AB  - We present a theoretical model of light-beam propagation in anisotropic and
      inhomogeneous dielectric structures obtained as a direct extension of the scalar
      fast-Fourier-transform beam-propagation method. We solve Maxwell's equations in a
      generalized geometrical optics approximation, in which the reflected fields are
      neglected. This is a full-vectorial model because it accounts for the
      polarization effects that are due to both the anisotropy and the inhomogeneity of
      the medium.

PMID- 18319998
TI  - All-optical switching in a distributed-feedback GaInAsP waveguide.
AB  - The characteristics of all-optical switching in a waveguide device with a
      distributed-feedback structure were experimentally investigated. The device was
      composed of a strip-loaded GaInAsP/InP waveguide and a distributed-feedback
      structure, which was fabricated by a combination of reactive-ion etching and
      electron-beam exposure. In the experiments, several optical switching operations
      were demonstrated. In particular, the all-optical set-reset operation and
      threshold operation were obtained.

PMID- 18319999
TI  - Optimal control theory for optical waveguide design: application to Y-branch
      structures.
AB  - A recently introduced optimal control theory method for optical waveguide design
      is applied to Y-branch waveguides and Mach-Zehnder modulators. The method
      simultaneously optimizes many parameters in a chosen design scheme; computational
      effort scales mildly with the number of parameters considered. Significant
      improvement in guiding efficiency relative to intuitively reasonable initial
      parameter choices is obtained in all cases.

PMID- 18320000
TI  - Laser-induced fluorescence measurements of translational temperature and relative
      cycle number by use of optically pumped trace-sodium vapor.
AB  - Sodium fluorescence induced by a narrow-bandwidth tunable laser has been used to
      measure temperature, pressure, axial velocity, and species concentrations in wind
      tunnels, rocket engine exhausts, and the upper atmosphere. Optical pumping of the
      ground states of the sodium, however, can radically alter the shape of the laser
      induced fluorescence excitation spectrum, complicating such measurements. Here a
      straightforward extension of rate equations originally proposed to account for
      the features of the pumped spectrum is used to make temperature measurements from
      spectra taken in pumped vapor. Also determined from the spectrum is the relative
      fluorescence cycle number, which has application to measurement of diffusion rate
      and transverse flow velocity. The accuracy of both the temperature and the cycle
      number measurements is comparable with that of temperature measurements made in
      the absence of pumping.

PMID- 18320001
TI  - Angular variation of thermal infrared emissivity for some natural surfaces from
      experimental measurements.
AB  - Multiangle algorithms for estimating sea and land surface temperature with Along
      Track Scanning Radiometer data require a precise knowledge of the angular
      variation of surface emissivity in the thermal infrared. Currently, few
      measurements of this variation exist. Here an experimental investigation of the
      angular variation of the infrared emissivity in the thermal infrared (8-14
      microm) band of some representative samples was made at angles of 0 degrees-65
      degrees (at 5 degrees increments) to the surface normal. The results show a
      decrease of the emissivity with increasing viewing angle, with water showing the
      highest angular dependence (approximately 7% from 0 degrees to 65 degrees views).
      Clay, sand, slime, and gravel show variations of approximately 1-3% for the same
      range of views, whereas a homogeneous grass cover does not show angular
      dependence. Finally, we include an evaluation of the impact that these data can
      produce on the algorithms for determining land and sea surface temperature from
      double-angle views.

PMID- 18320002
TI  - Backscattering target detection in a turbid medium by polarization
      discrimination.
AB  - We describe a method for increasing target contrast within a turbid medium by
      means of the polarization state of the scattered light. The backscattered Mueller
      matrices for various concentrations of 0.1-microm spherical scatterers were
      measured with and without a painted metal target. Simple discrimination based on
      detecting cross-polarized intensities is shown to be more effective than the use
      of total intensity information. As a result, the choice of polarization state is
      dictated primarily by the requirement to maximize depolarization at the target.
      This in general means that circularly polarized light is the optimum choice.

PMID- 18320003
TI  - Design of an efficient broadband far-infrared Fourier-transform spectrometer.
AB  - As part of a feasibility study for a far-infrared Fourier-transform spaceborne
      spectrometer, the criteria that drive the choice of the instrument configuration
      have been identified as broadband operation, dual input and output ports, optics
      of the interferometer with full tilt compensation, and measurement of both planes
      of polarization of the source on a single detector. Despite the fact that some of
      these requirements are apparently difficult to reconcile, a new configuration of
      the polarizing interferometer that meets all the above requirements has been
      identified. The considerations that led to the design of this new configuration
      are discussed.

PMID- 18320004
TI  - Pulsed, single-mode cavity ringdown spectroscopy.
AB  - We discuss the use of single-mode cavity ringdown spectroscopy with pulsed lasers
      for quantitative gas density and line strength measurements. The single-mode
      approach to cavity ringdown spectroscopy gives single exponential decay signals
      without mode beating, which allows measurements with uncertainties near the shot
      noise limit. The technique is demonstrated with a 10-cm-long ringdown cavity and
      a pulsed, frequency-stabilized optical parametric oscillator as the light source.
      A noise-equivalent absorption coefficient of 5 x 10(-10) cm(-1) Hz(-1/2) is
      demonstrated, and the relative standard deviation in the ringdown time
      (sigma(tau)/tau) extracted from a fit to an individual ringdown curve is found to
      be the same as that for an ensemble of hundreds of independent measurements.
      Repeated measurement of a line strength is shown to have a standard deviation
      <0.3%. The effects of normally distributed noise on quantities measured using
      cavity ringdown spectroscopy are discussed, formulas for the relative standard
      deviation in the ringdown time are given in the shot- and technical-noise limits,
      and the noise-equivalent absorption coefficient in these limits are compared for
      pulsed and continuous-wave light sources.

PMID- 18320005
TI  - Transmission features of frequency-selective components in the far infrared
      determined by terahertz time-domain spectroscopy.
AB  - Transmission and phase-shift characteristics of dichroic high-pass filters with
      cutoff frequencies as high as 1.11 THz and of a cross-shaped grid bandpass filter
      with a resonance frequency of 280 GHz were measured with an electro-optic
      sampling terahertz time-domain spectrometer operating between 0.1 and 2 THz. Good
      agreement with transmission theories is found. We also compare the transmission
      performance of cascaded dichroic filters with that of cross-shaped grid bandpass
      filters. Both types of bandpass filter permit frequency-selective ultrafast
      experiments in the far-infrared spectral region. In the millimeter and the
      submillimeter wavelength regions, which are difficult to access by conventional
      means, knowledge of the frequency response of frequency-selective components is
      important for applications in frequency mixing, multiplying, and multiplexing in
      quasi-optical systems.

PMID- 18320006
TI  - Toward the Total Synthesis of Scleritodermin A: Preparation of the C(1)-N(15)
      Fragment.
AB  - The synthesis of the C(1)-N(15) fragment of the marine natural product
      Scleritodermin A has been accomplished through a short and stereocontrolled
      sequence. Highlights of this route include the synthesis of the novel ACT
      fragment and the formation of the alpha-keto amide linkage by the use of a highly
      activated alpha, beta-ketonitrile.

PMID- 18320007
TI  - One-pot synthesis of polysubstituted indoles from aliphatic nitro compounds under
      mild conditions.
AB  - Polysubstituted indoles can be prepared directly from functionalized nitroalkanes
      under very mildly acidic conditions in a simple, one-pot, two-stage procedure.

PMID- 18320008
TI  - Dioxadispiroketal Compounds and a Potential Acyclic Precursor from Amomum
      aculeatum.
AB  - Four new compounds having an unusual 1,7-dioxadispiro[5.1.5.2]-12-ene-11-one
      tricyclic ring system (1-4), their potential precursor, 5R-hydroxy-1-(4-hydroxyl
      phenyl)-eicosan-3-one (5), and two known compounds, aculeatins A (6) and B (7),
      have been isolated from Amomum aculeatum. All compounds were characterized by
      spectroscopic methods and the configurations were established by 2D NOE
      correlations. Compounds 1-4, 6 and 7 showed cytotoxic activity against several
      human cancer cell lines.

PMID- 18320009
TI  - A context-sensitive active contour for 2D corpus callosum segmentation.
AB  - We propose a new context-sensitive active contour for 2D corpus callosum
      segmentation. After a seed contour consisting of interconnected parts is being
      initialized by the user, each part will start to deform according to its own
      motion law derived from high-level prior knowledge, and is constantly aware of
      its own orientation and destination during the deformation process. Experimental
      results demonstrate the accuracy and robustness of our algorithm.

PMID- 18320010
TI  - Defective differentiation of myeloid and plasmacytoid dendritic cells in advanced
      cancer patients is not normalized by tyrosine kinase inhibition of the vascular
      endothelial growth factor receptor.
AB  - Tumor-derived vascular endothelial growth factor (VEGF) has previously been
      identified as a causative factor in the disturbed differentiation of myeloid
      dendritic cells (DC) in advanced cancer patients. Here, we investigated the
      potential of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase
      (TK) inhibition to overcome this defective DC differentiation. To this end,
      peripheral blood DC (PBDC) precursor and subset frequencies were measured in 13
      patients with advanced cancer before and after treatment with AZD2171, a TK
      inhibitor (TKI) of VEGFR, coadministered with gefitinib, and an epidermal growth
      factor receptor (EGFR) TKI. Of note, not only myeloid DC but also plasmacytoid DC
      frequencies were significantly reduced in the blood of the cancer patients prior
      to treatment, as compared to healthy controls. Moreover, besides an accumulated
      population of immature myeloid cells (ImC), a population of myeloid suppressor
      cells (MSC) was significantly increased. Upon systemic VEGFR TK inhibition, DC
      frequencies did not increase, whereas the rate of circulating MSC showed a
      slight, but not significant, decrease. In conclusion, TK inhibition of VEGFR with
      AZD2171 does not restore the defective PBDC differentiation observed in advanced
      cancer patients.

PMID- 18320011
TI  - Human brain microvascular endothelial cells and umbilical vein endothelial cells
      differentially facilitate leukocyte recruitment and utilize chemokines for T cell
      migration.
AB  - Endothelial cells that functionally express blood brain barrier (BBB) properties
      are useful surrogates for studying leukocyte-endothelial cell interactions at the
      BBB. In this study, we compared two different endothelial cellular models:
      transfected human brain microvascular endothelial cells (THBMECs) and human
      umbilical vein endothelial cells (HUVECs). With each grow under optimal
      conditions, confluent THBMEC cultures showed continuous occludin and ZO-1
      immunoreactivity, while HUVEC cultures exhibited punctate ZO-1 expression at
      sites of cell-cell contact only. Confluent THBMEC cultures on 24-well collagen
      coated transwell inserts had significantly higher transendothelial electrical
      resistance (TEER) and lower solute permeability than HUVECs. Confluent THBMECs
      were more restrictive for mononuclear cell migration than HUVECs. Only THBMECs
      utilized abluminal CCL5 to facilitate T-lymphocyte migration in vitro although
      both THBMECs and HUVECs employed CCL3 to facilitate T cell migration. These data
      establish baseline conditions for using THBMECs to develop in vitro BBB models
      for studying leukocyte-endothelial interactions during neuroinflammation.

PMID- 18320012
TI  - The immune response is involved in atherosclerotic plaque calcification: could
      the RANKL/RANK/OPG system be a marker of plaque instability?
AB  - Atherogenesis is characterized by an intense inflammatory process, involving
      immune and vascular cells. These cells play a crucial role in all phases of
      atherosclerotic plaque formation and complication through cytokine, protease, and
      prothrombotic factor secretion. The accumulation of inflammatory cells and thus
      high amounts of soluble mediators are responsible for the evolution of some
      plaques to instable phenotype which may lead to rupture. One condition strongly
      associated with plaque rupture is calcification, a physiopathological process
      orchestrated by several soluble factors, including the receptor activator of
      nuclear factor (NF)kappaB ligand (RANKL)/receptor activator of nuclear factor
      (NF)kappaB (RANK)/osteoprotegerin (OPG) system. Although some studies showed some
      interesting correlations with acute ischemic events, at present, more evidences
      are needed to evaluate the predictive and diagnostic value of serum sRANKL and
      OPG levels for clinical use. The major limitation is probably the poor
      specificity of these factors for cardiovascular disease. The identification of
      tissue-specific isoforms could increase the importance of sRANKL and OPG in
      predicting calcified plaque rupture and the dramatic ischemic consequences in the
      brain and the heart.

PMID- 18320013
TI  - An innovative approach to functionality testing of analysers in the clinical
      laboratory.
AB  - The established protocols for evaluating new analytical systems produce
      indispensable information with regard to quality characteristics, but in general
      they fail to analyse the system performance under routine-like conditions. We
      describe a model which allows the testing of a new analytical system under
      conditions close to the routine in a controlled and systematic manner by using an
      appropriate software tool. Performing routine simulation experiments, either
      reflecting imprecision or method comparison characteristics, gives the user
      essential information on the overall system performance under real intended-use
      conditions.

PMID- 18320014
TI  - Tumor necrosis factor-alpha in peripical tissue exudates of teeth with apical
      periodontitis.
AB  - AIM: The aim of this study was to determine tumor necrosis factor-alpha (TNF
      alpha) levels in periapical exudates and to evaluate their relationship with
      radiological findings. METHODOLOGY: Periapical exudates were collected from root
      canals of 60 single-rooted teeth using absorbent paper points. TNF-alpha levels
      were determined by enzyme-linked immunosorbent assays. The samples were divided
      into three groups according to the periapical radiolucent area. RESULTS:
      Nonparametric Kruskal-Wallis test revealed significant differences between TNF
      alpha concentrations in control group (40, 57+/-28, 15 pg/mL) and group with
      larger radiolucent areas (2365, 79+/-582, 95 pg/mL), as well as between control
      and canals with small radiolucent areas (507, 66+/-278, 97) (P<.05). CONCLUSIONS:
      The levels of TNF-alpha increase significantly in teeth with periapical pathosis,
      from smaller to bigger lesions. This research and its results have shown that
      objective analysis of the TNF-alpha levels enables establishment of a
      relationship between different concentrations of TNF-alpha and different
      radiological changes.

PMID- 18320015
TI  - Early expression of FcgammaRI (CD64) on monocytes of cardiac surgical patients
      and higher density of monocyte anti-inflammatory scavenger CD163 receptor in "on
      pump" patients.
AB  - OBJECTIVE: Activation of innate immunity cells is inseparably linked to cardiac
      surgical operation. The aim of this study was to assess the kinetics in the
      expression of receptor for Fc part of IgG, FcgammaRI (CD64), and scavenger
      receptor CD163 on peripheral blood cells of cardiac surgical patients and to
      examine the effect of cardiac bypass as a separable influence on the systemic
      acute inflammatory response. METHODS: Forty patients, twenty in each group, were
      randomly assigned to CABG surgery performed either with "on-pump" or without "off
      pump" cardiopulmonary bypass. Standardized quantitative flow cytometry method was
      used to determine the expression of surface markers. RESULTS: The density of CD64
      molecule on monocytes reached maximum on the 1st postoperative day (P<.001)
      whereas the peak for CD64 molecule expression on granulocytes was postponed to
      the 3rd postoperative day (P<.001). The expression of CD163 scavenger molecule on
      monocytes reached maximum on the 1st postoperative day (P<.001). The density of
      CD163 molecule on monocytes on the 1st postoperative day is significantly higher
      in "on-pump" patients in comparison with "off-pump" patients (P<.001).
      CONCLUSION: In cardiac surgical patients the expression of activation marker
      FcgammaR1 (CD64) on monocytes is increased earlier in comparison with
      granulocytes in both "on-pump" and "off-pump" patients. The expression of
      scavenger molecule CD163 on monocytes is significantly higher in "on-pump"
      patients.

PMID- 18320016
TI  - Novel triazine JPC-2067-B inhibits Toxoplasma gondii in vitro and in vivo.
AB  - BACKGROUND AND METHODOLOGY: Toxoplasma gondii causes substantial morbidity,
      mortality, and costs for healthcare in the developed and developing world.
      Current medicines are not well tolerated and cause hypersensitivity reactions.
      The dihydrotriazine JPC-2067-B (4, 6-diamino-1, 2-dihydro-2, 2-dimethyl-1-(3'(2
      chloro-, 4-trifluoromethoxyphenoxy)propyloxy)-1, 3, 5-triazine), which inhibits
      dihydrofolate reductase (DHFR), is highly effective against Plasmodium
      falciparum, Plasmodium vivax, and apicomplexans related to T. gondii. JPC-2067-B
      is the primary metabolite of the orally active biguanide JPC-2056 1-(3'-(2-chloro
      4-trifluoromethoxyphenyloxy)propyl oxy)- 5-isopropylbiguanide, which is being
      advanced to clinical trials for malaria. Efficacy of the prodrug JPC-2056 and the
      active metabolite JPC-2067-B against T. gondii and T. gondii DHFR as well as
      toxicity toward mammalian cells were tested. PRINCIPAL FINDINGS AND CONCLUSIONS:
      Herein, we found that JPC-2067-B is highly effective against T. gondii. We
      demonstrate that JPC-2067-B inhibits T. gondii growth in culture (IC50 20 nM),
      inhibits the purified enzyme (IC50 6.5 nM), is more efficacious than
      pyrimethamine, and is cidal in vitro. JPC-2067-B administered parenterally and
      the orally administered pro-drug (JPC-2056) are also effective against T. gondii
      tachyzoites in vivo. A molecular model of T. gondii DHFR-TS complexed with JPC
      2067-B was developed. We found that the three main parasite clonal types and
      isolates from South and Central America, the United States, Canada, China, and
      Sri Lanka have the same amino acid sequences preserving key binding sites for the
      triazine. SIGNIFICANCE: JPC-2056/JPC-2067-B have potential to be more effective
      and possibly less toxic treatments for toxoplasmosis than currently available
      medicines.

PMID- 18320017
TI  - Schistosomiasis Japonica: The DALYs Recaptured.

PMID- 18320018
TI  - Decision-model estimation of the age-specific disability weight for
      schistosomiasis japonica: a systematic review of the literature.
AB  - Schistosomiasis is among the most prevalent parasitic infections worldwide.
      However, current Global Burden of Disease (GBD) disability-adjusted life year
      estimates indicate that its population-level impact is negligible. Recent studies
      suggest that GBD methodologies may significantly underestimate the burden of
      parasitic diseases, including schistosomiasis. Furthermore, strain-specific
      disability weights have not been established for schistosomiasis, and the
      magnitude of human disease burden due to Schistosoma japonicum remains
      controversial. We used a decision model to quantify an alternative disability
      weight estimate of the burden of human disease due to S. japonicum. We reviewed
      S. japonicum morbidity data, and constructed decision trees for all infected
      persons and two age-specific strata, <15 years (y) and > or =15 y. We conducted
      stochastic and probabilistic sensitivity analyses for each model. Infection with
      S. japonicum was associated with an average disability weight of 0.132, with age
      specific disability weights of 0.098 (<15 y) and 0.186 (> or =15 y). Re-estimated
      disability weights were seven to 46 times greater than current GBD measures; no
      simulations produced disability weight estimates lower than 0.009. Nutritional
      morbidities had the greatest contribution to the S. japonicum disability weight
      in the <15 y model, whereas major organ pathologies were the most critical
      variables in the older age group. GBD disability weights for schistosomiasis
      urgently need to be revised, and species-specific disability weights should be
      established. Even a marginal increase in current estimates would result in a
      substantial rise in the estimated global burden of schistosomiasis, and have
      considerable implications for public health prioritization and resource
      allocation for schistosomiasis research, monitoring, and control.

PMID- 18320019
TI  - Peptide mimicrying between SARS coronavirus spike protein and human proteins
      reacts with SARS patient serum.
AB  - Molecular mimicry, defined as similar structures shared by molecules from
      dissimilar genes or proteins, is a general strategy used by pathogens to infect
      host cells. Severe acute respiratory syndrome (SARS) is a new human respiratory
      infectious disease caused by SARS coronavirus (SARS-CoV). The spike (S) protein
      of SARS-CoV plays an important role in the virus entry into a cell. In this
      study, eleven synthetic peptides from the S protein were selected based on its
      sequence homology with human proteins. Two of the peptides D07 (residues 927-937)
      and D08 (residues 942-951) were recognized by the sera of SARS patients. Murine
      hyperimmune sera against these peptides bound to proteins of human lung
      epithelial cells A549. Another peptide D10 (residues 490-502) stimulated A549 to
      proliferate and secrete IL-8. The present results suggest that the selected S
      protein regions, which share sequence homology with human proteins, may play
      important roles in SARS-CoV infection.

PMID- 18320020
TI  - Synthesis, structure, electrochemistry, and spectral characterization of bis
      isatin thiocarbohydrazone metal complexes and their antitumor activity against
      ehrlich ascites carcinoma in swiss albino mice.
AB  - The synthesis, structure, electrochemistry, and biological studies of Co(II),
      Ni(II), Cu(II), and Zn(II) complexes of thiocarbohydrazone ligand are described.
      The ligand is synthesized starting from thiocarbohydrazide and isatin. It is
      evident from the IR data that in all the complexes, only one part of the ligand
      is coordinated to the metal ion resulting mononuclear complexes. The ligand
      coordinates essentially through the carbonyl oxygen of the isatin fragment, the
      nitrogen atom of the azomethine group, and sulfur atom after deprotonation to
      give five membered rings. H1 NMR spectrum of the ligand shows only one set of
      signals for the aromatic protons, while the NH of isatin and NH of hydrazone give
      rise to two different singlets in the 11-14 ppm range. The formulations,
      [Cu(L)Cl].2H2O, [Cu(L)(CH3COO)].2H2O, [Ni(L)Cl], [Ni(L)(CH3COO)], [Co(L2)], and
      [Zn(L2)].2H2O are in accordance with elemental analyses, physical, and
      spectroscopic measurements. The complexes are soluble in organic solvents. Molar
      conductance values in DMF indicate the nonelectrolytic nature of the complexes.
      Copper complex displays quasireversible cyclic voltametric responses with Ep near
      -0.659 v and 0.504 v Vs Ag/AgCl at the scan rate of 0.1 V/s. Copper(II) complexes
      show a single line EPR signals. For the observed magnetic moment and electronic
      spectral data possible explanation has been discussed. From all the available
      data, the probable structures for the complexes have been proposed. The compounds
      synthesized in present study have shown promising cytotoxic activity when
      screened using the in vitro method and at the same time were shown to have good
      activity when tested using the Ehrlich ascites carcinoma (EAC) model. The
      antimicrobial screening showed that the cobalt complex possesses enhanced
      antimicrobial activity towards fungi.

PMID- 18320021
TI  - Change in localization of alkaline phosphatase and mannosidase II by colchicine
      treatment of primary cultures of fetal rat hepatocytes.
AB  - We examined the changes in localization of alkaline phosphatase (ALP) and
      mannosidase II (man II), a Golgi marker, after colchicine treatment of primary
      cultures of fetal rat hepatocytes, using double immunofluorescence staining and
      confocal laser microscopy. In hepatocytes cultured in basal medium, ALP was
      localized in the perinuclear cytoplasm, and man II was observed in the Golgi
      region of the cytoplasm. When hepatocytes were cultured in dexamethasone
      supplemented medium, ALP was also localized in the plasma membrane surrounding
      the bile canaliculus-like structure that was formed between adjacent cells. In
      hepatocytes cultured in the same medium containing colchicine, the structure of
      microtubules in the cytoplasm was lost, man II exhibited granular distribution
      scattering throughout the cytoplasm, and ALP was localized in coarse granular
      sites of the cytoplasm. However, ALP was not colocalized at the same sites as man
      II. The present study indicated that colchicine inhibits the dexamethasone
      promoted translocation of ALP to the plasma membrane surrounding the bile
      canaliculus-like structure in primary cultures of fetal rat hepatocytes by
      disassembling microtubules and discomposing the Golgi complex.

PMID- 18320022
TI  - Toddlers' and Preschoolers' Experience in Family Day Care: Age Differences and
      Behavioral Correlates.
AB  - One hundred and twelve children, 56 toddlers and 56 preschoolers, were observed
      in their family child care settings to determine whether toddlers cared for in
      settings that also included preschoolers were, relative to the preschoolers,
      receiving more or less high-quality care and/or whether their functioning at
      child care appeared to be more or less dependent on aspects of the care
      providers' interactions with the children. Quality of care was analyzed along two
      dimensions: Sensitive/Supportive Care and Structured Care. Four indices of child
      functioning at child care were examined: integration in social activities,
      attention, positive mood, and angry/aggressive behavior. Results indicate that
      toddlers received less sensitive, supportive care than preschoolers in these
      mixed-age settings and toddlers were less socially integrated and less engaged in
      activities in the child care setting. Preschoolers displayed increased levels of
      angry/aggressive behavior relative to toddlers. In addition, associations of care
      provider behaviors and child functioning were larger for toddlers than
      preschoolers, suggesting that toddlers were more dependent on caregiver support
      for more successful functioning in these family child care settings. For both
      toddlers and preschoolers, care provider behavior and child functioning was
      generally poorer in settings with more children.

PMID- 18320023
TI  - Integration of gene dosage and gene expression in non-small cell lung cancer,
      identification of HSP90 as potential target.
AB  - BACKGROUND: Lung cancer causes approximately 1.2 million deaths per year
      worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung
      cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC)
      is essential to improve early diagnosis and treatment for this disease.
      METHODOLOGY AND PRINCIPAL FINDINGS: In an attempt to identify novel NSCLC related
      genes, we performed a genome-wide screening of chromosomal copy number changes
      affecting gene expression using microarray based comparative genomic
      hybridization and gene expression arrays on 32 radically resected tumor samples
      from stage I and II NSCLC patients. An integrative analysis tool was applied to
      determine whether chromosomal copy number affects gene expression. We identified
      a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which
      significantly influenced gene expression for HSP90, residing on 14q32. This
      deletion was correlated with better overall survival (P = 0.008), survival was
      also longer in patients whose tumors had low expression levels of HSP90. We
      extended the analysis to three independent validation sets of NSCLC patients, and
      confirmed low HSP90 expression to be related with longer overall survival (P =
      0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90
      inhibitor had potent antiproliferative activity in NSCLC cell lines. CONCLUSIONS:
      We suggest that targeting HSP90 will have clinical impact for NSCLC patients.

PMID- 18320024
TI  - The human TPR protein TTC4 is a putative Hsp90 co-chaperone which interacts with
      CDC6 and shows alterations in transformed cells.
AB  - BACKGROUND: The human TTC4 protein is a TPR (tetratricopeptide repeat) motif
      containing protein. The gene was originally identified as being localized in a
      genomic region linked to breast cancer and subsequent studies on melanoma cell
      lines revealed point mutations in the TTC4 protein that may be associated with
      the progression of malignant melanoma. METHODOLOGY/PRINCIPLE FINDINGS: Here we
      show that TTC4 is a nucleoplasmic protein which interacts with HSP90 and HSP70,
      and also with the replication protein CDC6. It has significant structural and
      functional similarities with a previously characterised Drosophila protein
      Dpit47. We show that TTC4 protein levels are raised in malignant melanoma cell
      lines compared to melanocytes. We also see increased TTC4 expression in a variety
      of tumour lines derived from other tissues. In addition we show that TTC4
      proteins bearing some of the mutations previously identified from patient samples
      lose their interaction with the CDC6 protein. CONCLUSIONS/SIGNIFICANCE: Based on
      these results and our previous work with the Drosophila Dpit47 protein we suggest
      that TTC4 is an HSP90 co-chaperone protein which forms a link between HSP90
      chaperone activity and DNA replication. We further suggest that the loss of the
      interaction with CDC6 or with additional client proteins could provide one route
      through which TTC4 could influence malignant development of cells.

PMID- 18320025
TI  - Frequent fires in ancient shrub tundra: implications of paleorecords for arctic
      environmental change.
AB  - Understanding feedbacks between terrestrial and atmospheric systems is vital for
      predicting the consequences of global change, particularly in the rapidly
      changing Arctic. Fire is a key process in this context, but the consequences of
      altered fire regimes in tundra ecosystems are rarely considered, largely because
      tundra fires occur infrequently on the modern landscape. We present
      paleoecological data that indicate frequent tundra fires in northcentral Alaska
      between 14,000 and 10,000 years ago. Charcoal and pollen from lake sediments
      reveal that ancient birch-dominated shrub tundra burned as often as modern boreal
      forests in the region, every 144 years on average (+/- 90 s.d.; n = 44). Although
      paleoclimate interpretations and data from modern tundra fires suggest that
      increased burning was aided by low effective moisture, vegetation cover clearly
      played a critical role in facilitating the paleofires by creating an abundance of
      fine fuels. These records suggest that greater fire activity will likely
      accompany temperature-related increases in shrub-dominated tundra predicted for
      the 21(st) century and beyond. Increased tundra burning will have broad impacts
      on physical and biological systems as well as on land-atmosphere interactions in
      the Arctic, including the potential to release stored organic carbon to the
      atmosphere.

PMID- 18320026
TI  - Induction of tachykinin production in airway epithelia in response to viral
      infection.
AB  - BACKGROUND: The tachykinins are implicated in neurogenic inflammation and the
      neuropeptide substance P in particular has been shown to be a proinflammatory
      mediator. A role for the tachykinins in host response to lung challenge has been
      previously demonstrated but has been focused predominantly on the release of the
      tachykinins from nerves innervating the lung. We have previously demonstrated the
      most dramatic phenotype described for the substance P encoding gene
      preprotachykinin-A (PPT-A) to date in controlling the host immune response to the
      murine gammaherpesvirus 68, in the lung. METHODOLOGY/PRINCIPAL FINDINGS: In this
      study we have utilised transgenic mice engineered to co-ordinately express the
      beta-galactosidase marker gene along with PPT-A to facilitate the tracking of PPT
      A expression. Using a combination of these mice and conventional immunohistology
      we now demonstrate that PPT-A gene expression and substance P peptide are induced
      in cells of the respiratory tract including tracheal, bronchiolar and alveolar
      epithelial cells and macrophages after viral infection. This induction was
      observed 24h post infection, prior to observable inflammation and the expression
      of pro-inflammatory chemokines in this model. Induced expression of the PPT-A
      gene and peptide persisted in the lower respiratory tract through day 7 post
      infection. CONCLUSIONS/SIGNIFICANCE: Non-neuronal PPT-A expression early after
      infection may have important clinical implications for the progression or
      management of lung disease or infection aside from the well characterised later
      involvement of the tachykinins during the inflammatory response.

PMID- 18320027
TI  - Case-control study of fetal microchimerism and breast cancer.
AB  - BACKGROUND: Prior pregnancy is known to protect against development of breast
      cancer. Recent studies have demonstrated that pregnancy has the capacity to
      establish small numbers of immunologically active fetal-derived cells in the
      mother, a phenomenon known as fetal microchimerism (FMc). We asked whether
      presence of FMc, routinely acquired during pregnancy, is a protective factor for
      breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: DNA extracts from peripheral blood
      specimens were obtained from a population-based case-control study of risk
      factors for breast cancer in women 21 to 45 years old. Specimens were tested with
      quantitative PCR for presence and concentrations of male DNA presumed to derive
      from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence
      intervals (CI) were estimated with consideration of multiple established
      reproductive and environmental risk factors for breast cancer. FMc results were
      generated on 99 parous women, 54 with primary invasive breast cancer and 45
      general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in
      controls and cases, respectively. Women harboring FMc were less likely to have
      had breast cancer (OR = 0.29, 95% CI 0.11-0.83; p = 0.02, adjusting for age,
      number of children, birth of a son, history of miscarriage, and total DNA
      tested). In addition, FMc concentrations were higher in controls versus cases (p
      = 0.01). Median concentrations were 2 (0-78) and 0 (0-374) fetal genomes/10(6)
      maternal genomes in controls and cases, respectively. CONCLUSIONS: Results
      suggest that the enigma of why some parous women are not afforded protection from
      breast cancer by pregnancy might in part be explained by differences in FMc.
      Mechanistic studies of FMc-derived protection against breast cancer are
      warranted.

PMID- 18320028
TI  - Peripherally-derived BDNF promotes regeneration of ascending sensory neurons
      after spinal cord injury.
AB  - BACKGROUND: The blood brain barrier (BBB) and truncated trkB receptor on
      astrocytes prevent the penetration of brain derived neurotrophic factor (BDNF)
      applied into the peripheral (PNS) and central nervous system (CNS) thus restrict
      its application in the treatment of nervous diseases. As BDNF is anterogradely
      transported by axons, we propose that peripherally derived and/or applied BDNF
      may act on the regeneration of central axons of ascending sensory neurons.
      METHODOLOGY/PRINCIPAL FINDINGS: The present study aimed to test the hypothesis by
      using conditioning lesion of the sciatic nerve as a model to increase the
      expression of endogenous BDNF in sensory neurons and by injecting exogenous BDNF
      into the peripheral nerve or tissues. Here we showed that most of regenerating
      sensory neurons expressed BDNF and p-CREB but not p75NTR. Conditioning-lesion
      induced regeneration of ascending sensory neuron and the increase in the number
      of p-Erk positive and GAP-43 positive neurons was blocked by the injection of the
      BDNF antiserum in the periphery. Enhanced neurite outgrowth of dorsal root
      ganglia (DRG) neurons in vitro by conditioning lesion was also inhibited by the
      neutralization with the BDNF antiserum. The delivery of exogenous BDNF into the
      sciatic nerve or the footpad significantly increased the number of regenerating
      DRG neurons and regenerating sensory axons in the injured spinal cord. In a
      contusion injury model, an injection of BDNF into the footpad promoted recovery
      of motor functions. CONCLUSIONS/SIGNIFICANCE: Our data suggest that endogenous
      BDNF in DRG and spinal cord is required for the enhanced regeneration of
      ascending sensory neurons after conditioning lesion of sciatic nerve and
      peripherally applied BDNF may have therapeutic effects on the spinal cord injury.

PMID- 18320029
TI  - Signaling signatures and functional properties of anti-human CD28 superagonistic
      antibodies.
AB  - Superagonistic CD28 antibodies (CD28SAs) activate T lymphocytes without
      concomitant perturbation of the TCR/CD3-complex. In rodents these reagents induce
      the preferential expansion of regulatory T cells and can be used for the
      treatment of autoimmune diseases. Unexpectedly, the humanized CD28 superagonist
      TGN1412 caused severe and life threatening adverse effects during a recently
      conducted phase I clinical trail. The underlying molecular mechanisms are as yet
      unclear. We show that TGN1412 as well as the commercially available CD28
      superagonist ANC28.1 induce a delayed but extremely sustained calcium response in
      human naive and memory CD4+ T cells but not in cynomolgus T lymphocytes. The
      sustained Ca++-signal was associated with the activation of multiple
      intracellular signaling pathways and together these events culminated in the
      rapid de novo synthesis of high amounts of pro-inflammatory cytokines, most
      notably IFN-gamma and TNF-alpha. Importantly, sustained transmembranous calcium
      flux, activation of Src-kinases as well as activation of PI3K were found to be
      absolutely required for CD28SA-mediated production of IFN-gamma and IL-2.
      Collectively, our data suggest a molecular basis for the severe side effects
      caused by TGN1412 and impinge upon the relevance of non-human primates as
      preclinical models for reagents that are supposed to modify the function of human
      T cells.

PMID- 18320030
TI  - SnoRNA Snord116 (Pwcr1/MBII-85) deletion causes growth deficiency and hyperphagia
      in mice.
AB  - Prader-Willi syndrome (PWS) is the leading genetic cause of obesity. After
      initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if
      intake is not restricted. Short stature with abnormal growth hormone secretion,
      hypogonadism, cognitive impairment, anxiety and behavior problems are other
      features. PWS is caused by lack of expression of imprinted genes in a
      approximately 4 mb region of chromosome band 15q11.2. Our previous translocation
      studies predicted a major role for the C/D box small nucleolar RNA cluster
      SNORD116 (PWCR1/HBII-85) in PWS. To test this hypothesis, we created a
      approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85) in
      C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression
      of this snoRNA. They have early-onset postnatal growth deficiency, but normal
      fertility and lifespan. While pituitary structure and somatotrophs are normal,
      liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice
      are deficient in motor learning and have increased anxiety. Around three months
      of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On
      reduced caloric intake, Snord116del mice maintain their weight better than wild
      type littermates, excluding increased energy requirement as a cause of
      hyperphagia. Normal compensatory feeding after fasting, and ability to maintain
      body temperature in the cold indicate normal energy homeostasis regulation.
      Metabolic chamber studies reveal that Snord116del mice maintain energy
      homeostasis by altered fuel usage. Prolonged mealtime and increased circulating
      ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the
      first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in
      growth and feeding regulation.

PMID- 18320031
TI  - SIRT1 overexpression antagonizes cellular senescence with activated ERK/S6k1
      signaling in human diploid fibroblasts.
AB  - Sir2, a NAD-dependent deacetylase, modulates lifespan in yeasts, worms and flies.
      The SIRT1, mammalian homologue of Sir2, regulates signaling for favoring survival
      in stress. But whether SIRT1 has the function to influence cell viability and
      senescence under non-stressed conditions in human diploid fibroblasts is far from
      unknown. Our data showed that enforced SIRT1 expression promoted cell
      proliferation and antagonized cellular senescence with the characteristic
      features of delayed Senescence-Associated beta-galactosidase (SA-beta-gal)
      staining, reduced Senescence-Associated Heterochromatic Foci (SAHF) formation and
      G1 phase arrest, increased cell growth rate and extended cellular lifespan in
      human fibroblasts, while dominant-negative SIRT1 allele (H363Y) did not
      significantly affect cell growth and senescence but displayed a bit decreased
      lifespan. Western blot results showed that SIRT1 reduced the expression of
      p16(INK4A) and promoted phosphorylation of Rb. Our data also exposed that
      overexpression of SIRT1 was accompanied by enhanced activation of ERK and S6K1
      signaling. These effects were mimicked in both WI38 cells and 2BS cells by
      concentration-dependent resveratrol, a SIRT1 activator. It was noted that
      treatment of SIRT1-.transfected cells with Rapamycin, a mTOR inhibitor, reduced
      the phosphorylation of S6K1 and the expression of Id1, implying that SIRT1
      induced phosphorylation of S6K1 may be partly for the decreased expression of
      p16(INK4A) and promoted phosphorylation of Rb in 2BS. It was also observed that
      the expression of SIRT1 and phosphorylation of ERK and S6K1 was declined in
      senescent 2BS. These findings suggested that SIRT1-promoted cell proliferation
      and antagonized cellular senescence in human diploid fibroblasts may be, in part,
      via the activation of ERK/ S6K1 signaling.

PMID- 18320032
TI  - When did HIV incidence peak in Harare, Zimbabwe? Back-calculation from mortality
      statistics.
AB  - HIV prevalence has recently begun to decline in Zimbabwe, a result of both high
      levels of AIDS mortality and a reduction in incident infections. An important
      component in understanding the dynamics in HIV prevalence is knowledge of past
      trends in incidence, such as when incidence peaked and at what level. However,
      empirical measurements of incidence over an extended time period are not
      available from Zimbabwe or elsewhere in sub-Saharan Africa. Using mortality data,
      we use a back-calculation technique to reconstruct historic trends in incidence.
      From AIDS mortality data, extracted from death registration in Harare, together
      with an estimate of survival post-infection, HIV incidence trends were
      reconstructed that would give rise to the observed patterns of AIDS mortality.
      Models were fitted assuming three parametric forms of the incidence curve and
      under nine different assumptions regarding combinations of trends in non-AIDS
      mortality and patterns of survival post-infection with HIV. HIV prevalence was
      forward-projected from the fitted incidence and mortality curves. Models that
      constrained the incidence pattern to a cubic spline function were flexible and
      produced well-fitting, realistic patterns of incidence. In models assuming
      constant levels of non-AIDS mortality, annual incidence peaked between 4 and 5%
      between 1988 and 1990. Under other assumptions the peak level ranged from 3 to 8%
      per annum. However, scenarios assuming increasing levels of non-AIDS mortality
      resulted in implausibly low estimates of peak prevalence (11%), whereas models
      with decreasing underlying crude mortality could be consistent with the
      prevalence and mortality data. HIV incidence is most likely to have peaked in
      Harare between 1988 and 1990, which may have preceded the peak elsewhere in
      Zimbabwe. This finding, considered alongside the timing and location of HIV
      prevention activities, will give insight into the decline of HIV prevalence in
      Zimbabwe.

PMID- 18320033
TI  - Identifying selected regions from heterozygosity and divergence using a light
      coverage genomic dataset from two human populations.
AB  - When a selective sweep occurs in the chromosomal region around a target gene in
      two populations that have recently separated, it produces three dramatic genomic
      consequences: 1) decreased multi-locus heterozygosity in the region; 2) elevated
      or diminished genetic divergence (F(ST)) of multiple polymorphic variants
      adjacent to the selected locus between the divergent populations, due to the
      alternative fixation of alleles; and 3) a consequent regional increase in the
      variance of F(ST) (S(2)F(ST)) for the same clustered variants, due to the
      increased alternative fixation of alleles in the loci surrounding the selection
      target. In the first part of our study, to search for potential targets of
      directional selection, we developed and validated a resampling-based
      computational approach; we then scanned an array of 31 different-sized moving
      windows of SNP variants (5-65 SNPs) across the human genome in a set of European
      and African American population samples with 183,997 SNP loci after correcting
      for the recombination rate variation. The analysis revealed 180 regions of recent
      selection with very strong evidence in either population or both. In the second
      part of our study, we compared the newly discovered putative regions to those
      sites previously postulated in the literature, using methods based on inspecting
      patterns of linkage disequilibrium, population divergence and other
      methodologies. The newly found regions were cross-validated with those found in
      nine other studies that have searched for selection signals. Our study was
      replicated especially well in those regions confirmed by three or more studies.
      These validated regions were independently verified, using a combination of
      different methods and different databases in other studies, and should include
      fewer false positives. The main strength of our analysis method compared to
      others is that it does not require dense genotyping and therefore can be used
      with data from population-based genome SNP scans from smaller studies of humans
      or other species.

PMID- 18320034
TI  - Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.
AB  - BACKGROUND: Obesity is associated with macrophage infiltration of adipose tissue,
      which may link adipose inflammation to insulin resistance. However, the impact of
      inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate
      resistant acid phosphatase (TRAP) is an enzyme expressed by subsets of
      macrophages and osteoclasts that exists either as an enzymatically inactive
      monomer or as an active, proteolytically processed dimer. PRINCIPAL FINDINGS:
      Using mice over expressing TRAP, we show that over-expression of monomeric, but
      not the dimeric form in adipose tissue leads to early onset spontaneous
      hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric,
      but not proteolytically processed TRAP induced proliferation and differentiation
      of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was
      highly expressed in the adipose tissue of obese individuals. In both the mouse
      model and in the obese humans the source of TRAP in adipose tissue was
      macrophages. In addition, the obese TRAP over expressing mice exhibited signs of
      a low-grade inflammatory reaction in adipose tissue without evidence of abnormal
      adipocyte lipolysis, lipogenesis or insulin sensitivity. CONCLUSION: Monomeric
      TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic
      obesity with normal adipocyte lipid metabolism and insulin sensitivity.

PMID- 18320035
TI  - Ganglion cell adaptability: does the coupling of horizontal cells play a role?
AB  - BACKGROUND: The visual system can adjust itself to different visual environments.
      One of the most well known examples of this is the shift in spatial tuning that
      occurs in retinal ganglion cells with the change from night to day vision. This
      shift is thought to be produced by a change in the ganglion cell receptive field
      surround, mediated by a decrease in the coupling of horizontal cells.
      METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, we used a transgenic
      mouse line, a connexin57-deficient line, in which horizontal cell coupling was
      abolished. Measurements, both at the ganglion cell level and the level of
      behavioral performance, showed no differences between wild-type retinas and
      retinas with decoupled horizontal cells from connexin57-deficient mice.
      CONCLUSION/SIGNIFICANCE: This analysis showed that the coupling and uncoupling of
      horizontal cells does not play a dominant role in spatial tuning and its
      adjustability to night and day light conditions. Instead, our data suggest that
      another mechanism, likely arising in the inner retina, must be responsible.

PMID- 18320036
TI  - Heterogeneous adaptive trajectories of small populations on complex fitness
      landscapes.
AB  - BACKGROUND: Small populations are thought to be adaptively handicapped, not only
      because they suffer more from deleterious mutations but also because they have
      limited access to new beneficial mutations, particularly those conferring large
      benefits. METHODOLOGY/PRINCIPAL FINDINGS: Here, we test this widely held
      conjecture using both simulations and experiments with small and large bacterial
      populations evolving in either a simple or a complex nutrient environment.
      Consistent with expectations, we find that small populations are adaptively
      constrained in the simple environment; however, in the complex environment small
      populations not only follow more heterogeneous adaptive trajectories, but can
      also attain higher fitness than the large populations. Large populations are
      constrained to near deterministic fixation of rare large-benefit mutations. While
      such determinism speeds adaptation on the smooth adaptive landscape represented
      by the simple environment, it can limit the ability of large populations from
      effectively exploring the underlying topography of rugged adaptive landscapes
      characterized by complex environments. CONCLUSIONS: Our results show that
      adaptive constraints often faced by small populations can be circumvented during
      evolution on rugged adaptive landscapes.

PMID- 18320037
TI  - Relativistic compression and expansion of experiential time in the left and right
      space.
AB  - Time, space and numbers are closely linked in the physical world. However, the
      relativistic-like effects on time perception of spatial and magnitude factors
      remain poorly investigated. Here we wanted to investigate whether duration
      judgments of digit visual stimuli are biased depending on the side of space where
      the stimuli are presented and on the magnitude of the stimulus itself. Different
      groups of healthy subjects performed duration judgment tasks on various types of
      visual stimuli. In the first two experiments visual stimuli were constituted by
      digit pairs (1 and 9), presented in the centre of the screen or in the right and
      left space. In a third experiment visual stimuli were constituted by black
      circles. The duration of the reference stimulus was fixed at 300 ms. Subjects had
      to indicate the relative duration of the test stimulus compared with the
      reference one. The main results showed that, regardless of digit magnitude,
      duration of stimuli presented in the left hemispace is underestimated and that of
      stimuli presented in the right hemispace is overestimated. On the other hand, in
      midline position, duration judgments are affected by the numerical magnitude of
      the presented stimulus, with time underestimation of stimuli of low magnitude and
      time overestimation of stimuli of high magnitude. These results argue for the
      presence of strict interactions between space, time and magnitude representation
      on the human brain.

PMID- 18320038
TI  - A visual data mining tool that facilitates reconstruction of transcription
      regulatory networks.
AB  - BACKGROUND: Although the use of microarray technology has seen exponential
      growth, analysis of microarray data remains a challenge to many investigators.
      One difficulty lies in the interpretation of a list of differentially expressed
      genes, or in how to plan new experiments given that knowledge. Clustering methods
      can be used to identify groups of genes with similar expression patterns, and
      genes with unknown function can be provisionally annotated based on the concept
      of "guilt by association", where function is tentatively inferred from the known
      functions of genes with similar expression patterns. These methods frequently
      suffer from two limitations: (1) visualization usually only gives access to group
      membership, rather than specific information about nearest neighbors, and (2) the
      resolution or quality of the relationships are not easily inferred.
      METHODOLOGY/PRINCIPAL FINDINGS: We have addressed these issues by improving the
      precision of similarity detection over that of a single experiment and by
      creating a tool to visualize tractable association networks: we (1) performed
      meta-analysis computation of correlation coefficients for all gene pairs in a
      heterogeneous data set collected from 2,145 publicly available micorarray samples
      in mouse, (2) filtered the resulting distribution of over 130 million correlation
      coefficients to build new, more tractable distributions from the strongest
      correlations, and (3) designed and implemented a new Web based tool (StarNet,
      http://vanburenlab.medicine.tamhsc.edu/starnet.html) for visualization of sub
      networks of the correlation coefficients built according to user specified
      parameters. CONCLUSIONS/SIGNIFICANCE: Correlations were calculated across a
      heterogeneous collection of publicly available microarray data. Users can access
      this analysis using a new freely available Web-based application for visualizing
      tractable correlation networks that are flexibly specified by the user. This new
      resource enables rapid hypothesis development for transcription regulatory
      relationships.

PMID- 18320039
TI  - Adaptor SKAP-55 binds p21 activating exchange factor RasGRP1 and negatively
      regulates the p21-ERK pathway in T-cells.
AB  - While the adaptor SKAP-55 mediates LFA-1 adhesion on T-cells, it is not known
      whether the adaptor regulates other aspects of signaling. SKAP-55 could
      potentially act as a node to coordinate the modulation of adhesion with
      downstream signaling. In this regard, the GTPase p21(ras) and the extracellular
      signal-regulated kinase (ERK) pathway play central roles in T-cell function. In
      this study, we report that SKAP-55 has opposing effects on adhesion and the
      activation of the p21(ras) -ERK pathway in T-cells. SKAP-55 deficient primary T
      cells showed a defect in LFA-1 adhesion concurrent with the hyper-activation of
      the ERK pathway relative to wild-type cells. RNAi knock down (KD) of SKAP-55 in T
      cell lines also showed an increase in p21(ras) activation, while over-expression
      of SKAP-55 inhibited activation of ERK and its transcriptional target ELK. Three
      observations implicated the p21(ras) activating exchange factor RasGRP1 in the
      process. Firstly, SKAP-55 bound to RasGRP1 via its C-terminus, while secondly,
      the loss of binding abrogated SKAP-55 inhibition of ERK and ELK activation.
      Thirdly, SKAP-55-/- primary T-cells showed an increased presence of RasGRP1 in
      the trans-Golgi network (TGN) following TCR activation, the site where p21(ras)
      becomes activated. Our findings indicate that SKAP-55 has a dual role in
      regulating p21(ras)-ERK pathway via RasGRP1, as a possible mechanism to restrict
      activation during T-cell adhesion.

PMID- 18320040
TI  - The effect of central loops in miRNA:MRE duplexes on the efficiency of miRNA
      mediated gene regulation.
AB  - MicroRNAs (miRNAs) guide posttranscriptional repression of mRNAs. Hundreds of
      miRNAs have been identified but the target identification of mammalian mRNAs is
      still a difficult task due to a poor understanding of the interaction between
      miRNAs and the miRNA recognizing element (MRE). In recent research, the
      importance of the 5' end of the miRNA:MRE duplex has been emphasized and the
      effect of the tail region addressed, but the role of the central loop has largely
      remained unexplored. Here we examined the effect of the loop region in miRNA:MRE
      duplexes and found that the location of the central loop is one of the important
      factors affecting the efficiency of gene regulation mediated by miRNAs. It was
      further determined that the addition of a loop score combining both location and
      size as a new criterion for predicting MREs and their cognate miRNAs
      significantly decreased the false positive rates and increased the specificity of
      MRE prediction.

PMID- 18320041
TI  - The balance between plasmacytoid DC versus conventional DC determines pulmonary
      immunity to virus infections.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) infects nearly all infants by age 2
      and is a leading cause of bronchiolitis. RSV may employ several mechanisms to
      induce immune dysregulation, including dendritic cell (DC) modulation during the
      immune response to RSV. METHODS AND FINDINGS: Expansion of cDC and pDC by Flt3L
      treatment promoted an anti-viral response with reduced pathophysiology
      characterized by decreased airway hyperreactivity, reduced Th2 cytokines,
      increased Th1 cytokines, and a reduction in airway inflammation and mucus
      overexpression. These protective aspects of DC expansion could be completely
      reversed by depleting pDCs during the RSV infection. Expansion of DCs by Flt3L
      treatment enhanced in CD8+ T cell responses, which was reversed by depletion of
      pDC. CONCLUSIONS: These results indicate that a balance between cDC and pDC in
      the lung and its lymph nodes is crucial for the outcome of a pulmonary infection.
      Increased pDC numbers induced by Flt3L treatment have a protective impact on the
      nature of the overall immune environment.

PMID- 18320042
TI  - Has the DOTS strategy improved case finding or treatment success? An empirical
      assessment.
AB  - BACKGROUND: Nearly fifteen years after the start of WHO's DOTS strategy,
      tuberculosis remains a major global health problem. Given the lack of empirical
      evidence that DOTS reduces tuberculosis burden, considerable debate has arisen
      about its place in the future of global tuberculosis control efforts. An
      independent evaluation of DOTS, one of the most widely-implemented and longest
      running interventions in global health, is a prerequisite for meaningful
      improvements to tuberculosis control efforts, including WHO's new Stop TB
      Strategy. We investigate the impact of the expansion of the DOTS strategy on
      tuberculosis case finding and treatment success, using only empirical data.
      METHODS AND FINDINGS: We study the effect of DOTS using time-series cross
      sectional methods. We first estimate the impact of DOTS expansion on case
      detection, using reported case notification data and controlling for other
      determinants of change in notifications, including HIV prevalence, GDP, and
      country-specific effects. We then estimate the effect of DOTS expansion on
      treatment success. DOTS programme variables had no statistically significant
      impact on case detection in a wide range of models and specifications. DOTS
      population coverage had a significant effect on overall treatment success rates,
      such that countries with full DOTS coverage benefit from at least an 18% increase
      in treatment success (95% CI: 5-31%). CONCLUSIONS: The DOTS technical package
      improved overall treatment success. By contrast, DOTS expansion had no effect on
      case detection. This finding is less optimistic than previous analyses. Better
      epidemiological and programme data would facilitate future monitoring and
      evaluation efforts.

PMID- 18320043
TI  - Transcriptome of Aphanomyces euteiches: new oomycete putative pathogenicity
      factors and metabolic pathways.
AB  - Aphanomyces euteiches is an oomycete pathogen that causes seedling blight and
      root rot of legumes, such as alfalfa and pea. The genus Aphanomyces is
      phylogenically distinct from well-studied oomycetes such as Phytophthora sp., and
      contains species pathogenic on plants and aquatic animals. To provide the first
      foray into gene diversity of A. euteiches, two cDNA libraries were constructed
      using mRNA extracted from mycelium grown in an artificial liquid medium or in
      contact to plant roots. A unigene set of 7,977 sequences was obtained from 18,864
      high-quality expressed sequenced tags (ESTs) and characterized for potential
      functions. Comparisons with oomycete proteomes revealed major differences between
      the gene content of A. euteiches and those of Phytophthora species, leading to
      the identification of biosynthetic pathways absent in Phytophthora, of new
      putative pathogenicity genes and of expansion of gene families encoding
      extracellular proteins, notably different classes of proteases. Among the genes
      specific of A. euteiches are members of a new family of extracellular proteins
      putatively involved in adhesion, containing up to four protein domains similar to
      fungal cellulose binding domains. Comparison of A. euteiches sequences with
      proteomes of fully sequenced eukaryotic pathogens, including fungi, apicomplexa
      and trypanosomatids, allowed the identification of A. euteiches genes with close
      orthologs in these microorganisms but absent in other oomycetes sequenced so far,
      notably transporters and non-ribosomal peptide synthetases, and suggests the
      presence of a defense mechanism against oxidative stress which was initially
      characterized in the pathogenic trypanosomatids.

PMID- 18320044
TI  - B cell response is required for granuloma formation in the early infection of
      Schistosoma japonicum.
AB  - Schistosoma egg-induced liver granuloma is a dynamic inflammatory reaction that
      results from complex immune responses to the infection. However, the role of B
      cells in inflammatory granuloma development is not yet fully understood. We
      report here that B cell function is required for S. japonicum egg-induced
      granuloma pathology in early infection. Both OBF-1 knockout mice and microMT mice
      develop severely reduced hepatic granulomas at five weeks post-infection compared
      to their wild-type counterparts. In contrast, they display no significant
      difference in granuloma pathology at eight weeks post-infection. Moreover, we
      find that B cells and antibodies accumulate in the granulomas of wild-type mice
      early in the infection, indicating a contribution of the B cell response to the
      granulomatous inflammation. Furthermore, defects in B cell function markedly
      reduce liver egg burden. These results suggest an important role for B cells in
      early granuloma pathology. Surprisingly, we found that the S. japonicum infection
      destroys the structure of the lymphoid follicles. This disruptive effect is
      correlated with a severely impaired T cell-dependent antibody response upon
      challenge with ovalbumin. Thus, these findings reveal a novel aspect of the
      interaction between Schistosoma and the host immune system.

PMID- 18320045
TI  - Overestimates of survival after HAART: implications for global scale-up efforts.
AB  - BACKGROUND: Monitoring the effectiveness of global antiretroviral therapy scale
      up efforts in resource-limited settings is a global health priority, but is
      complicated by high rates of losses to follow-up after treatment initiation.
      Determining definitive outcomes of these lost patients, and the effects of losses
      to follow-up on estimates of survival and risk factors for death after HAART, are
      key to monitoring the effectiveness of global HAART scale-up efforts.
      METHODOLOGY/PRINCIPAL FINDINGS: A cohort study comparing clinical outcomes and
      risk factors for death after HAART initiation as reported before and after
      tracing of patients lost to follow-up was conducted in Botswana's National
      Antiretroviral Therapy Program. 410 HIV-infected adults consecutively presenting
      for HAART were evaluated. The main outcome measures were death or loss to follow
      up within the first year after HAART initiation. Of 68 patients initially
      categorized as lost, over half (58.8%) were confirmed dead after tracing. Patient
      tracing resulted in reporting of significantly lower survival rates when death
      was used as the outcome and losses to follow-up were censored [1-year Kaplan
      Meier survival estimate 0.92 (95% confidence interval, 0.88-0.94 before tracing
      and 0.83 (95% confidence interval, 0.79-0.86) after tracing, log rank P<0.001].
      In addition, a significantly increased risk of death after HAART among men
      [adjusted hazard ratio 1.74 (95% confidence interval, 1.05-2.87)] would have been
      missed had patients not been traced [adjusted hazard ratio 1.41 (95% confidence
      interval, 0.65-3.05)]. CONCLUSIONS/SIGNIFICANCE: Due to high rates of death among
      patients lost to follow-up after HAART, survival rates may be inaccurate and
      important risk factors for death may be missed if patients are not actively
      traced. Patient tracing and uniform reporting of outcomes after HAART are needed
      to enable accurate monitoring of global HAART scale-up efforts.

PMID- 18320046
TI  - Common variants within MECP2 confer risk of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a predominantly female autoimmune disease
      that affects multiple organ systems. Herein, we report on an X-chromosome gene
      association with SLE. Methyl-CpG-binding protein 2 (MECP2) is located on
      chromosome Xq28 and encodes for a protein that plays a critical role in
      epigenetic transcriptional regulation of methylation-sensitive genes. Utilizing a
      candidate gene association approach, we genotyped 21 SNPs within and around MECP2
      in SLE patients and controls. We identify and replicate association between SLE
      and the genomic element containing MECP2 in two independent SLE cohorts from two
      ethnically divergent populations. These findings are potentially related to the
      overexpression of methylation-sensitive genes in SLE.

PMID- 18320047
TI  - Exploring action dynamics as an index of paired-associate learning.
AB  - Much evidence exists supporting a richer interaction between cognition and action
      than commonly assumed. Such findings demonstrate that short-timescale processes,
      such as motor execution, may relate in systematic ways to longer-timescale
      cognitive processes, such as learning. We further substantiate one direction of
      this interaction: the flow of cognition into action systems. Two experiments
      explored match-to-sample paired-associate learning, in which participants learned
      randomized pairs of unfamiliar symbols. During the experiments, their hand
      movements were continuously tracked using the Nintendo Wiimote. Across learning,
      participant arm movements are initiated and completed more quickly, exhibit lower
      fluctuation, and exert more perturbation on the Wiimote during the button press.
      A second experiment demonstrated that action dynamics index novel learning
      scenarios, and not simply acclimatization to the Wiimote interface. Results
      support a graded and systematic covariation between cognition and action, and
      recommend ways in which this theoretical perspective may contribute to applied
      learning contexts.

PMID- 18320048
TI  - Nanofibrous scaffolds incorporating PDGF-BB microspheres induce chemokine
      expression and tissue neogenesis in vivo.
AB  - Platelet-derived growth factor (PDGF) exerts multiple cellular effects that
      stimulate wound repair in multiple tissues. However, a major obstacle for its
      successful clinical application is the delivery system, which ultimately controls
      the in vivo release rate of PDGF. Polylactic-co-glycolic acid (PLGA) microspheres
      (MS) in nanofibrous scaffolds (NFS) have been shown to control the release of
      rhPDGF-BB in vitro. In order to investigate the effects of rhPDGF-BB release from
      MS in NFS on gene expression and enhancement of soft tissue engineering, rhPDGF
      BB was incorporated into differing molecular weight (MW) polymeric MS. By
      controlling the MW of the MS over a range of 6.5 KDa-64 KDa, release rates of
      PDGF can be regulated over periods of weeks to months in vitro. The NFS-MS
      scaffolds were divided into multiple groups based on MS release characteristics
      and PDGF concentration ranging from 2.5-25.0 microg and evaluated in vivo in a
      soft tissue wound repair model in the dorsa of rats. At 3, 7, 14 and 21 days post
      implantation, the scaffold implants were harvested followed by assessments of
      cell penetration, vasculogenesis and tissue neogenesis. Gene expression profiles
      using cDNA microarrays were performed on the PDGF-releasing NFS. The percentage
      of tissue invasion into MS-containing NFS at 7 days was higher in the PDGF groups
      when compared to controls. Blood vessel number in the HMW groups containing
      either 2.5 or 25 microg PDGF was increased above those of other groups at 7d
      (p<0.01). Results from cDNA array showed that PDGF strongly enhanced in vivo gene
      expression of the CXC chemokine family members such as CXCL1, CXCL2 and CXCL5.
      Thus, sustained release of rhPDGF-BB, controlled by slow-releasing MS associated
      with the NFS delivery system, enhanced cell migration and angiogenesis in vivo,
      and may be related to an induced expression of chemokine-related genes. This
      approach offers a technology to accurately control growth factor release to
      promote soft tissue engineering in vivo.

PMID- 18320049
TI  - Tempo and mode of diversification of lake Tanganyika cichlid fishes.
AB  - BACKGROUND: Understanding the causes of disparities in species diversity across
      taxonomic groups and regions is a fundamental aim in evolutionary biology.
      Addressing these questions is difficult because of the need for densely sampled
      phylogenies and suitable empirical systems. METHODOLOGY/PRINCIPAL FINDINGS: Here
      we investigate the cichlid fish radiation of Lake Tanganyika and show that per
      lineage diversification rates have been more than six times slower than in the
      species flocks of Lakes Victoria and Malawi. The result holds even at peak
      periods of diversification in Lake Tanganyika, ruling out the age of the lake as
      an explanation for slow average rates, and is robust to uncertainties over the
      calibration of cichlid radiations in geological time. Moreover, Lake Tanganyika
      lineages, irrespective of different biological characteristics (e.g. sexually
      dichromatic versus sexually monochromatic clades), have diversified at similar
      rates, falling within typical estimates across a range of plant and animal
      clades. For example, the mostly sexually dichromatic haplochromines, which have
      speciated explosively in Lakes Victoria and Malawi, have displayed modest rates
      in Lake Tanganyika (where they are called Tropheini). CONCLUSION/SIGNIFICANCE:
      Our results show that either the Lake Tanganyika environment is less conducive
      for cichlid speciation or the remarkable diversifying abilities of the
      haplochromines were inhibited by the prior occupancy of older radiations.
      Although the results indicate a dominant role for the environment in shaping
      cichlid diversification, differences in the timing of diversification among the
      Tanganyikan tribes indicate that biological differences were still important for
      the dynamics of species build-up in the lake. While we cannot resolve the timing
      of the radiation relative to the origin of the lake, because of the lack of
      robust geological date calibrations for cichlids, our results are consistent with
      a scenario that the different clades reflect independent adaptive radiations into
      different broad niches in the lake.

PMID- 18320050
TI  - Quantitative evaluation of DNA methylation patterns for ALVE and TVB genes in a
      neoplastic disease susceptible and resistant chicken model.
AB  - Chicken endogenous viruses, ALVE (Avian Leukosis Virus subgroup E), are inherited
      as LTR (long terminal repeat) retrotransposons, which are negatively correlated
      with disease resistance, and any changes in DNA methylation may contribute to the
      susceptibility to neoplastic disease. The relationship between ALVE methylation
      status and neoplastic disease in the chicken is undefined. White Leghorn inbred
      lines 7(2) and 6(3) at the ADOL have been respectively selected for resistance
      and susceptibility to tumors that are induced by avian viruses. In this study,
      the DNA methylation patterns of 3 approximately 6 CpG sites of four conserved
      regions in ALVE, including one unique region in ALVE1, the promoter region in the
      TVB (tumor virus receptor of ALV subgroup B, D and E) locus, were analyzed in the
      two lines using pyrosequencing methods in four tissues, i.e., liver, spleen,
      blood and hypothalamus. A significant CpG hypermethylation level was seen in line
      7(2) in all four tissues, e.g., 91.86 +/- 1.63% for ALVE region2 in blood,
      whereas the same region was hemimethylated (46.16 +/- 2.56%) in line 6(3). CpG
      methylation contents of the ALVE regions were significantly lower in line 6(3)
      than in line 7(2) in all tissues (P < 0.01) except the ALVE region 3/4 in liver.
      RNA expressions of ALVE regions 2 and 3 (PPT-U3) were significantly higher in
      line 6(3) than in line 7(2) (P < 0.01). The methylation levels of six recombinant
      congenic strains (RCSs) closely resembled to the background line 6(3) in ALVE
      region 2, which imply the methylation pattern of ALVE-region 2 may be a biomarker
      in resistant disease breeding. The methylation level of the promoter region in
      the TVB was significantly different in blood (P < 0.05) and hypothalamus (P <
      0.0001), respectively. Our data disclosed a hypermethylation pattern of ALVE that
      may be relevant for resistance against ALV induced tumors in chickens.

PMID- 18320051
TI  - Identification and characterization of a novel Plasmodium falciparum merozoite
      apical protein involved in erythrocyte binding and invasion.
AB  - Proteins that coat Plasmodium falciparum merozoite surface and those secreted
      from its apical secretory organelles are considered promising candidates for the
      vaccine against malaria. In the present study, we have identified an asparagine
      rich parasite protein (PfAARP; Gene ID PFD1105w), that harbors a predicted signal
      sequence, a C-terminal transmembrane region and whose transcription and
      translation patterns are similar to some well characterized merozoite
      surface/apical proteins. PfAARP was localized to the apical end of the merozoites
      by GFP-targeting approach using an inducible, schizont-stage expression system,
      by immunofluorescence assays using anti-PfAARP antibodies. Immuno-electron
      microsopic studies showed that PfAARP is localized in the apical ends of the
      rhoptries in the merozoites. RBC binding assays with PfAARP expressed on COS
      cells surface showed that it binds to RBCs through its N-terminal region with a
      receptor on the RBC surface that is sensitive to trypsin and neuraminidase
      treatments. Sequencing of PfAARP from different P. falciparum strains as well as
      field isolates showed that the N-terminal region is highly conserved. Recombinant
      protein corresponding to the N-terminal region of PfAARP (PfAARP-N) was produced
      in its functional form in E. coli. PfAARP-N showed reactivity with immune sera
      from individuals residing in P. falciparum endemic area. The anti-PfAARP-N rabbit
      antibodies significantly inhibited parasite invasion in vitro. Our data on
      localization, functional assays and invasion inhibition, suggest a role of PfAARP
      in erythrocyte binding and invasion by the merozoite.

PMID- 18320052
TI  - Early and late pathogenic events of newborn mice encephalitis experimentally
      induced by itacaiunas and curionopolis bracorhabdoviruses infection.
AB  - In previous reports we proposed a new genus for Rhabdoviridae and described
      neurotropic preference and gross neuropathology in newborn albino Swiss mice
      after Curionopolis and Itacaiunas infections. In the present report a time-course
      study of experimental encephalitis induced by Itacaiunas and Curionopolis virus
      was conducted both in vivo and in vitro to investigate cellular targets and the
      sequence of neuroinvasion. We also investigate, after intranasal inoculation,
      clinical signs, histopathology and apoptosis in correlation with viral
      immunolabeling at different time points. Curionopolis and Itacaiunas viral
      antigens were first detected in the parenchyma of olfactory pathways at 2 and 3
      days post-inoculation (dpi) and the first clinical signs were observed at 4 and 8
      dpi, respectively. After Curionopolis infection, the mortality rate was 100%
      between 5 and 6 dpi, and 35% between 8 and 15 dpi after Itacaiunas infection. We
      identified CNS mice cell types both in vivo and in vitro and the temporal
      sequence of neuroanatomical olfactory areas infected by Itacaiunas and
      Curionopolis virus. Distinct virulences were reflected in the neuropathological
      changes including TUNEL immunolabeling and cytopathic effects, more intense and
      precocious after intracerebral or in vitro inoculations of Curionopolis than
      after Itacaiunas virus. In vitro studies revealed neuronal but not astrocyte or
      microglial cytopathic effects at 2 dpi, with monolayer destruction occurring at 5
      and 7 dpi with Curionopolis and Itacaiunas virus, respectively. Ultrastructural
      changes included virus budding associated with interstitial and perivascular
      edema, endothelial hypertrophy, a reduced and/or collapsed small vessel luminal
      area, thickening of the capillary basement membrane, and presence of phagocytosed
      apoptotic bodies. Glial cells with viral budding similar to oligodendrocytes were
      infected with Itacaiunas virus but not with Curionopolis virus. Thus,
      Curionopolis and Itacaiunas viruses share many pathological and clinical features
      present in other rhabdoviruses but distinct virulence and glial targets in
      newborn albino Swiss mice brain.

PMID- 18320053
TI  - Nonvirally modified autologous primary hepatocytes correct diabetes and prevent
      target organ injury in a large preclinical model.
AB  - BACKGROUND: Current gene- and cell-based therapies have significant limitations
      which impede widespread clinical application. Taking diabetes mellitus as a
      paradigm, we have sought to overcome these limitations by ex vivo electrotransfer
      of a nonviral insulin expression vector into primary hepatocytes followed by
      immediate autologous reimplantation in a preclinical model of diabetes. METHODS
      AND RESULTS: In a single 3-hour procedure, hepatocytes were isolated from a
      surgically resected liver wedge, electroporated with an insulin expression
      plasmid ex vivo and reimplanted intraparenchymally under ultrasonic guidance into
      the liver in each of 10 streptozotocin-induced diabetic Yorkshire pigs. The
      vector was comprised of a bifunctional, glucose-responsive promoter linked to
      human insulin cDNA. Ambient glucose concentrations appropriately altered human
      insulin mRNA expression and C-peptide secretion within minutes in vitro and in
      vivo. Treated swine showed correction of hyperglycemia, glucose intolerance,
      dyslipidemia and other metabolic abnormalities for > or = 47 weeks. Metabolic
      correction correlated significantly with the number of hepatocytes implanted.
      Importantly, we observed no hypoglycemia even under fasting conditions. Direct
      intrahepatic implantation of hepatocytes did not alter biochemical indices of
      liver function or induce abnormal hepatic lobular architecture. About 70% of
      implanted hepatocytes functionally engrafted, appeared histologically normal,
      retained vector DNA and expressed human insulin for > or = 47 weeks. Based on
      structural tissue analyses and transcriptome data, we showed that early
      correction of diabetes attenuated and even prevented pathological changes in the
      eye, kidney, liver and aorta. CONCLUSIONS: We demonstrate that autologous
      hepatocytes can be efficiently, simply and safely modified by electroporation of
      a nonviral vector to express, process and secrete insulin durably. This strategy,
      which achieved significant and sustained therapeutic efficacy in a large
      preclinical model without adverse effects, warrants consideration for clinical
      development especially as it could have broader future applications for the
      treatment of other acquired and inherited diseases for which systemic
      reconstitution of a specific protein deficiency is critical.

PMID- 18320054
TI  - Auditory cortical contrast enhancing by global winner-take-all inhibitory
      interactions.
AB  - Brains decompose the world into discrete objects of perception, thereby facing
      the problem of how to segregate and selectively address similar objects that are
      concurrently present in a scene. Theoretical models propose that this could be
      achieved by neuronal implementations of so-called winner-take-all algorithms
      where neuronal representations of objects or object features interact in a
      competitive manner. Here we present evidence for the existence of such a
      mechanism in an animal species. We present electrophysiological,
      neuropharmacological and neuroanatomical data which suggest a novel view of the
      role of GABA(A)-mediated inhibition in primary auditory cortex (AI), where
      intracortical GABA(A)-mediated inhibition operates on a global scale within a
      circular map of sound periodicity representation in AI, with functionally
      inhibitory projections of similar effect from any location throughout the whole
      map. These interactions could underlie the proposed competitive "winner-take-all"
      algorithm to support object segregation, e.g., segregation of different speakers
      in cocktail-party situations.

PMID- 18320055
TI  - Retention of memory through metamorphosis: can a moth remember what it learned as
      a caterpillar?
AB  - Insects that undergo complete metamorphosis experience enormous changes in both
      morphology and lifestyle. The current study examines whether larval experience
      can persist through pupation into adulthood in Lepidoptera, and assesses two
      possible mechanisms that could underlie such behavior: exposure of emerging
      adults to chemicals from the larval environment, or associative learning
      transferred to adulthood via maintenance of intact synaptic connections. Fifth
      instar Manduca sexta caterpillars received an electrical shock associatively
      paired with a specific odor in order to create a conditioned odor aversion, and
      were assayed for learning in a Y choice apparatus as larvae and again as adult
      moths. We show that larvae learned to avoid the training odor, and that this
      aversion was still present in the adults. The adult aversion did not result from
      carryover of chemicals from the larval environment, as neither applying odorants
      to naive pupae nor washing the pupae of trained caterpillars resulted in a change
      in behavior. In addition, we report that larvae trained at third instar still
      showed odor aversion after two molts, as fifth instars, but did not avoid the
      odor as adults, consistent with the idea that post-metamorphic recall involves
      regions of the brain that are not produced until later in larval development. The
      present study, the first to demonstrate conclusively that associative memory
      survives metamorphosis in Lepidoptera, provokes intriguing new questions about
      the organization and persistence of the central nervous system during
      metamorphosis. Our results have both ecological and evolutionary implications, as
      retention of memory through metamorphosis could influence host choice by
      polyphagous insects, shape habitat selection, and lead to eventual sympatric
      speciation.

PMID- 18320057
TI  - Estimating heritabilities and genetic correlations: comparing the 'animal model'
      with parent-offspring regression using data from a natural population.
AB  - Quantitative genetic parameters are nowadays more frequently estimated with
      restricted maximum likelihood using the 'animal model' than with traditional
      methods such as parent-offspring regressions. These methods have however rarely
      been evaluated using equivalent data sets. We compare heritabilities and genetic
      correlations from animal model and parent-offspring analyses, respectively, using
      data on eight morphological traits in the great reed warbler (Acrocephalus
      arundinaceus). Animal models were run using either mean trait values or
      individual repeated measurements to be able to separate between effects of
      including more extended pedigree information and effects of replicated sampling
      from the same individuals. We show that the inclusion of more pedigree
      information by the use of mean traits animal models had limited effect on the
      standard error and magnitude of heritabilities. In contrast, the use of repeated
      measures animal model generally had a positive effect on the sampling accuracy
      and resulted in lower heritabilities; the latter due to lower additive variance
      and higher phenotypic variance. For most trait combinations, both animal model
      methods gave genetic correlations that were lower than the parent-offspring
      estimates, whereas the standard errors were lower only for the mean traits animal
      model. We conclude that differences in heritabilities between the animal model
      and parent-offspring regressions were mostly due to the inclusion of individual
      replicates to the animal model rather than the inclusion of more extended
      pedigree information. Genetic correlations were, on the other hand, primarily
      affected by the inclusion of more pedigree information. This study is to our
      knowledge the most comprehensive empirical evaluation of the performance of the
      animal model in relation to parent-offspring regressions in a wild population.
      Our conclusions should be valuable for reconciliation of data obtained in earlier
      studies as well as for future meta-analyses utilizing estimates from both
      traditional methods and the animal model.

PMID- 18320056
TI  - MicroRNA biogenesis is required for mouse primordial germ cell development and
      spermatogenesis.
AB  - BACKGROUND: MicroRNAs (miRNAs) are critical regulators of transcriptional and
      post-transcriptional gene silencing, which are involved in multiple developmental
      processes in many organisms. Apart from miRNAs, mouse germ cells express another
      type of small RNA, piwi-interacting RNAs (piRNAs). Although it has been clear
      that piRNAs play a role in repression of retrotransposons during spermatogenesis,
      the function of miRNA in mouse germ cells has been unclear. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we first revealed the expression pattern of miRNAs by
      using a real-time PCR-based 220-plex miRNA expression profiling method. During
      development of germ cells, miR-17-92 cluster, which is thought to promote cell
      cycling, and the ES cell-specific cluster encoding miR-290 to -295 (miR-290-295
      cluster) were highly expressed in primordial germ cells (PGCs) and spermatogonia.
      A set of miRNAs was developmentally regulated. We next analysed function of miRNA
      biogenesis in germ cell development by using conditional Dicer-knockout mice in
      which Dicer gene was deleted specifically in the germ cells. Dicer-deleted PGCs
      and spermatogonia exhibited poor proliferation. Retrotransposon activity was
      unexpectedly suppressed in Dicer-deleted PGCs, but not affected in the
      spermatogonia. In Dicer-deleted testis, spermatogenesis was retarded at an early
      stage when proliferation and/or early differentiation. Additionally, we analysed
      spermatogenesis in conditional Argonaute2-deficient mice. In contrast to Dicer
      deficient testis, spermatogenesis in Argonaute2-deficient testis was
      indistinguishable from that in wild type. CONCLUSION/SIGNIFICANCE: These results
      illustrate that miRNAs are important for the proliferation of PGCs and
      spermatogonia, but dispensable for the repression of retrotransposons in
      developing germ cells. Consistently, miRNAs promoting cell cycling are highly
      expressed in PGCs and spermatogonia. Furthermore, based on normal spermatogenesis
      in Argonaute2-deficient testis, the critical function of Dicer in spermatogenesis
      is independent of Argonaute2.

PMID- 18320058
TI  - Architecture of an antagonistic tree/fungus network: the asymmetric influence of
      past evolutionary history.
AB  - BACKGROUND: Compartmentalization and nestedness are common patterns in ecological
      networks. The aim of this study was to elucidate some of the processes shaping
      these patterns in a well resolved network of host/pathogen interactions.
      METHODOLOGY/PRINCIPAL FINDINGS: Based on a long-term (1972-2005) survey of forest
      health at the regional scale (all French forests; 15 million ha), we uncovered an
      almost fully connected network of 51 tree taxa and 157 parasitic fungal species.
      Our analyses revealed that the compartmentalization of the network maps out the
      ancient evolutionary history of seed plants, but not the ancient evolutionary
      history of fungal species. The very early divergence of the major fungal phyla
      may account for this asymmetric influence of past evolutionary history. Unlike
      compartmentalization, nestedness did not reflect any consistent phylogenetic
      signal. Instead, it seemed to reflect the ecological features of the current
      species, such as the relative abundance of tree species and the life-history
      strategies of fungal pathogens. We discussed how the evolution of host range in
      fungal species may account for the observed nested patterns.
      CONCLUSION/SIGNIFICANCE: Overall, our analyses emphasized how the current
      complexity of ecological networks results from the diversification of the species
      and their interactions over evolutionary times. They confirmed that the current
      architecture of ecological networks is not only dependent on recent ecological
      processes.

PMID- 18320059
TI  - S100A7-downregulation inhibits epidermal growth factor-induced signaling in
      breast cancer cells and blocks osteoclast formation.
AB  - S100A7 is a small calcium binding protein, which has been shown to be
      differentially expressed in psoriatic skin lesions, as well as in squamous cell
      tumors of the skin, lung and breast. Although its expression has been correlated
      to HER+ high-grade tumors and to a high risk of progression, the molecular
      mechanisms of these S100A7-mediated tumorigenic effects are not well known. Here,
      we showed for the first time that epidermal growth factor (EGF) induces S100A7
      expression in both MCF-7 and MDA-MB-468 cell lines. We also observed a decrease
      in EGF-directed migration in shRNA-downregulated MDA-MB-468 cell lines.
      Furthermore, our signaling studies revealed that EGF induced simultaneous EGF
      receptor phosphorylation at Tyr1173 and HER2 phosphorylation at Tyr1248 in S100A7
      downregulated cell lines as compared to the vector-transfected controls. In
      addition, reduced phosphorylation of Src at tyrosine 416 and p-SHP2 at tyrosine
      542 was observed in these downregulated cell lines. Further studies revealed that
      S100A7-downregulated cells had reduced angiogenesis in vivo based on matrigel
      plug assays. Our results also showed decreased tumor-induced osteoclastic
      resorption in an intra-tibial bone injection model involving SCID mice. S100A7
      downregulated cells had decreased osteoclast number and size as compared to the
      vector controls, and this decrease was associated with variations in IL-8
      expression in in vitro cell cultures. This is a novel report on the role of
      S100A7 in EGF-induced signaling in breast cancer cells and in osteoclast
      formation.

PMID- 18320060
TI  - Automated 3D phenotype analysis using data mining.
AB  - The ability to analyze and classify three-dimensional (3D) biological morphology
      has lagged behind the analysis of other biological data types such as gene
      sequences. Here, we introduce the techniques of data mining to the study of 3D
      biological shapes to bring the analyses of phenomes closer to the efficiency of
      studying genomes. We compiled five training sets of highly variable morphologies
      of mammalian teeth from the MorphoBrowser database. Samples were labeled either
      by dietary class or by conventional dental types (e.g. carnassial, selenodont).
      We automatically extracted a multitude of topological attributes using Geographic
      Information Systems (GIS)-like procedures that were then used in several
      combinations of feature selection schemes and probabilistic classification models
      to build and optimize classifiers for predicting the labels of the training sets.
      In terms of classification accuracy, computational time and size of the feature
      sets used, non-repeated best-first search combined with 1-nearest neighbor
      classifier was the best approach. However, several other classification models
      combined with the same searching scheme proved practical. The current study
      represents a first step in the automatic analysis of 3D phenotypes, which will be
      increasingly valuable with the future increase in 3D morphology and phenomics
      databases.

PMID- 18320061
TI  - Hibernation in an antarctic fish: on ice for winter.
AB  - Active metabolic suppression in anticipation of winter conditions has been
      demonstrated in species of mammals, birds, reptiles and amphibians, but not fish.
      This is because the reduction in metabolic rate in fish is directly proportional
      to the decrease in water temperature and they appear to be incapable of further
      suppressing their metabolic rate independently of temperature. However, the
      Antarctic fish (Notothenia coriiceps) is unusual because it undergoes winter
      metabolic suppression irrespective of water temperature. We assessed the seasonal
      ecological strategy by monitoring swimming activity, growth, feeding and heart
      rate (f(H)) in N. coriiceps as they free-ranged within sub-zero waters. The
      metabolic rate of wild fish was extrapolated from f(H )recordings, from oxygen
      consumption calibrations established in the laboratory prior to fish release.
      Throughout the summer months N. coriiceps spent a considerable proportion of its
      time foraging, resulting in a growth rate (G(w)) of 0.18 +/- 0.2% day(-1). In
      contrast, during winter much of the time was spent sedentary within a refuge and
      fish showed a net loss in G(w) (-0.05 +/- 0.05% day(-1)). Whilst inactive during
      winter, N. coriiceps displayed a very low f(H), reduced sensory and motor
      capabilities, and standard metabolic rate was one third lower than in summer. In
      a similar manner to other hibernating species, dormancy was interrupted with
      periodic arousals. These arousals, which lasted a few hours, occurred every 4-12
      days. During arousal activity, f(H) and metabolism increased to summer levels.
      This endogenous suppression and activation of metabolic processes, independent of
      body temperature, demonstrates that N. coriiceps were effectively 'putting
      themselves on ice' during winter months until food resources improved. This study
      demonstrates that at least some fish species can enter a dormant state similar to
      hibernation that is not temperature driven and presumably provides seasonal
      energetic benefits.

PMID- 18320062
TI  - Seed dispersal anachronisms: rethinking the fruits extinct megafauna ate.
AB  - BACKGROUND: Some neotropical, fleshy-fruited plants have fruits structurally
      similar to paleotropical fruits dispersed by megafauna (mammals > 10(3) kg), yet
      these dispersers were extinct in South America 10-15 Kyr BP. Anachronic dispersal
      systems are best explained by interactions with extinct animals and show impaired
      dispersal resulting in altered seed dispersal dynamics. METHODOLOGY/PRINCIPAL
      FINDINGS: We introduce an operational definition of megafaunal fruits and perform
      a comparative analysis of 103 Neotropical fruit species fitting this dispersal
      mode. We define two megafaunal fruit types based on previous analyses of elephant
      fruits: fruits 4-10 cm in diameter with up to five large seeds, and fruits > 10
      cm diameter with numerous small seeds. Megafaunal fruits are well represented in
      unrelated families such as Sapotaceae, Fabaceae, Solanaceae, Apocynaceae,
      Malvaceae, Caryocaraceae, and Arecaceae and combine an overbuilt design (large
      fruit mass and size) with either a single or few (< 3 seeds) extremely large
      seeds or many small seeds (usually > 100 seeds). Within-family and within-genus
      contrasts between megafaunal and non-megafaunal groups of species indicate a
      marked difference in fruit diameter and fruit mass but less so for individual
      seed mass, with a significant trend for megafaunal fruits to have larger seeds
      and seediness. CONCLUSIONS/SIGNIFICANCE: Megafaunal fruits allow plants to
      circumvent the trade-off between seed size and dispersal by relying on frugivores
      able to disperse enormous seed loads over long-distances. Present-day seed
      dispersal by scatter-hoarding rodents, introduced livestock, runoff, flooding,
      gravity, and human-mediated dispersal allowed survival of megafauna-dependent
      fruit species after extinction of the major seed dispersers. Megafauna extinction
      had several potential consequences, such as a scale shift reducing the seed
      dispersal distances, increasingly clumped spatial patterns, reduced geographic
      ranges and limited genetic variation and increased among-population structuring.
      These effects could be extended to other plant species dispersed by large
      vertebrates in present-day, defaunated communities.

PMID- 18320063
TI  - T cell receptor engagement triggers its CD3epsilon and CD3zeta subunits to adopt
      a compact, locked conformation.
AB  - How the T cell antigen receptor (TCR) discriminates between molecularly related
      peptide/Major Histocompatibility Complex (pMHC) ligands and converts this
      information into different possible signaling outcomes is still not understood.
      One current model proposes that strong pMHC ligands, but not weak ones, induce a
      conformational change in the TCR. Evidence supporting this comes from a pull-down
      assay that detects ligand-induced binding of the TCR to the N-terminal SH3 domain
      of the adapter protein Nck, and also from studies with a neoepitope-specific
      antibody. Both methods rely on the exposure of a polyproline sequence in the
      CD3epsilon subunit of the TCR, and neither indicates whether the conformational
      change is transmitted to other CD3 subunits. Using a protease-sensitivity assay,
      we now show that the cytoplasmic tails of CD3epsilon and CD3zeta subunits become
      fully protected from degradation upon TCR triggering. These results suggest that
      the TCR conformational change is transmitted to the tails of CD3epsilon and
      CD3zeta, and perhaps all CD3 subunits. Furthermore, the resistance to protease
      digestion suggests that CD3 cytoplasmic tails adopt a compact structure in the
      triggered TCR. These results are consistent with a model in which transduction of
      the conformational change induced upon TCR triggering promotes condensation and
      shielding of the CD3 cytoplasmic tails.

PMID- 18320064
TI  - Open-label comparative clinical study of chlorproguanil-dapsone fixed dose
      combination (Lapdap) alone or with three different doses of artesunate for
      uncomplicated Plasmodium falciparum malaria.
AB  - The objective of this study was to determine the appropriate dose of artesunate
      for use in a fixed dose combination therapy with chlorproguanil-dapsone (CPG-DDS)
      for the treatment of uncomplicated falciparum malaria. METHODS: Open-label
      clinical trial comparing CPG-DDS alone or with artesunate 4, 2, or 1 mg/kg at
      medical centers in Blantyre, Malawi and Farafenni, The Gambia. The trial was
      conducted between June 2002 and February 2005, including 116 adults (median age
      27 years) and 107 children (median age 38 months) with acute uncomplicated
      Plasmodium falciparum malaria. Subjects were randomized into 4 groups to receive
      CPG-DDS alone or plus 4, 2 or 1 mg/kg of artesunate once daily for 3 days.
      Assessments took place on Days 0-3 in hospital and follow-up on Days 7 and 14 as
      out-patients. Efficacy was evaluated in the Day 3 per-protocol (PP) population
      using mean time to reduce baseline parasitemia by 90% (PC90). A number of
      secondary outcomes were also included. Appropriate artesunate dose was determined
      using a pre-defined decision matrix based on primary and secondary outcomes.
      Treatment emergent adverse events were recorded from clinical assessments and
      blood parameters. Safety was evaluated in the intent to treat (ITT) population.
      RESULTS: In the Day 3 PP population for the adult group (N = 85), mean time to
      PC90 was 19.1 h in the CPG-DDS group, significantly longer than for the
      +artesunate 1 mg/kg (12.5 h; treatment difference -6.6 h [95%CI -11.8, -1.5]), 2
      mg/kg (10.7 h; -8.4 h [95%CI -13.6, -3.2]) and 4 mg/kg (10.3 h; -8.7 h [95%CI 
      14.1, -3.2]) groups. For children in the Day 3 PP population (N = 92), mean time
      to PC90 was 21.1 h in the CPG-DDS group, similar to the +artesunate 1 mg/kg group
      (17.7 h; -3.3 h [95%CI -8.6, 2.0]), though the +artesunate 2 mg/kg and 4 mg/kg
      groups had significantly shorter mean times to PC90 versus CPG-DDS; 14.4 h
      (treatment difference -6.4 h [95%CI -11.7, -1.0]) and 12.8 h (-7.4 h [95%CI 
      12.9, -1.8]), respectively. An analysis of mean time to PC90 for the Day 14 PP
      and ITT populations was consistent with the primary analysis. Treatment emergent,
      drug-related adverse events were experienced in 35.3% (41/116) of adults and
      70.1% (75/107) of children; mostly hematological and gastroenterological. The
      nature and incidence of adverse events was similar between the groups. No dose
      related changes in laboratory parameters were observed. Nine serious adverse
      events due to any cause occurred in five subjects including two cases of
      hemolysis believed to be associated with drug treatment (one adult, one child).
      One adult died of anaphylactic shock, not associated with investigational
      therapy. CONCLUSIONS: CPG-DDS plus artesunate demonstrated advantages over CPG
      DDS alone for the primary efficacy endpoint (mean time to PC90) except in
      children for the 1 mg/kg artesunate dose. Based on a pre-defined decision matrix,
      the primary endpoint in the child group supported an artesunate dose of 4 mg/kg.
      Secondary endpoints also supported a 4 mg/kg artesunate dose to take forward into
      the remainder of the development program. TRIAL REGISTRATION: ClinicalTrials.gov
      NCT00519467.

PMID- 18320065
TI  - Cellular magnetic resonance imaging: in vivo imaging of melanoma cells in lymph
      nodes of mice.
AB  - Metastasis is responsible for most deaths due to malignant melanoma. The clinical
      significance of micrometastases in the lymph is a hotly debated topic, but an
      improved understanding of the lymphatic spread of cancer remains important for
      improving cancer survival. Cellular magnetic resonance imaging (MRI) is a newly
      emerging field of imaging research that is expected to have a large impact on
      cancer research. In this study, we demonstrate the cellular MRI technology
      required to reliably image the lymphatic system in mice and to detect iron
      labeled metastatic melanoma cells within the mouse lymph nodes. Melanoma cells
      were implanted directly into the inguinal lymph nodes in mice, and micro-MRI was
      performed using a customized 1.5-T clinical MRI system. We show cell detection of
      as few as 100 iron-labeled cells within the lymph node, with injections of larger
      cell numbers producing increasingly obvious regions of signal void. In addition,
      we show that cellular MRI allows monitoring of the fate of these cells over time
      as they develop into intranodal tumors. This technology will allow noninvasive
      investigations of cellular events in cancer metastasis within an entire animal
      and will facilitate progress in understanding the mechanisms of metastasis within
      the lymphatic system.

PMID- 18320066
TI  - SiRNA-mediated reduction of alpha-actinin-1 inhibits pressure-induced murine
      tumor cell wound implantation and enhances tumor-free survival.
AB  - Viable cancer cells can commonly be recovered from surgical sites and venous
      blood during tumor resection. The adhesion of these cells to surrounding tissues
      may impact patient outcomes. Iatrogenic exposure to increased extracellular
      pressure modulates integrin binding affinity and stimulates colon cancer cell
      adhesion in vitro through an alpha-actinin-1-dependent signaling pathway. We
      hypothesized that preoperative small interfering RNA-mediated silencing of alpha
      actinin-1 in tumor tissue could disrupt pressure-stimulated cancer cell adhesion
      to murine surgical wounds and thereby enhance subsequent tumor-free survival.
      Reducing alpha-actinin-1 in CT26 murine adenocarcinoma cells blocked cell
      adhesion to collagen in vitro and similarly inhibited pressure-induced CT26
      implantation in murine surgical wounds in vivo. Surgical wound contamination with
      pressure-activated CT26 cells significantly reduced tumor-free survival compared
      to contamination with tumor cells maintained under ambient pressure. However,
      mice treated with pressure-activated CT26 cells preoperatively transfected with
      alpha-actinin-1-specific small interfering RNA displayed reduced surgical site
      implantation and increased tumor-free survival compared to mice exposed to
      pressure-activated cells expressing normal levels of alpha-actinin-1 protein.
      These results suggest that pressure activation of malignant cells promotes tumor
      development and impairs tumor-free survival. alpha-Actinin-1 may be an effective
      therapeutic target to inhibit perioperative pressure-stimulated tumor cell
      implantation.

PMID- 18320067
TI  - Downregulation of Plk1 expression by receptor-mediated uptake of antisense
      oligonucleotide-loaded nanoparticles.
AB  - Human serum albumin (HSA) nanoparticles represent a promising tool for targeted
      drug delivery to tumor cells. The coupling of the antibody trastuzumab to
      nanoparticles uses the capability of human epidermal growth factor receptor 2
      (HER2)-positive cells to incorporate agents linked to HER2. In our present study,
      we developed targeted nanoparticles loaded with antisense oligonucleotides (ASOs)
      against polo-like kinase 1 (Plk1). We evaluated the receptor-mediated uptake into
      HER2-positive and -negative breast cancer and murine cell lines. We performed
      quantitative real-time PCR and Western blot analyses to monitor the impact on
      Plk1 expression in HER2-positive breast cancer cells. Antibody-conjugated
      nanoparticles showed a specific targeting to HER2-overexpressing cells with
      cellular uptake by receptor-mediated endocytosis and a release into HER2-positive
      BT-474 cells. We observed a significant reduction of Plk1 mRNA and protein
      expression and increased activation of Caspase 3/7. Thus, this is the first
      report about ASO-loaded HSA nanoparticles, where an impact on gene expression
      could be observed. The data provide the basis for the further development of
      carrier systems for Plk1-specific ASOs to reduce off-target effects evoked by
      systemically administered ASOs and to achieve a better penetration into primary
      and metastatic target cells. Treatment of tumors using trastuzumab-conjugated ASO
      loaded HSA nanoparticles could be a promising approach to reach this goal.

PMID- 18320068
TI  - FK506 binding protein mediates glioma cell growth and sensitivity to rapamycin
      treatment by regulating NF-kappaB signaling pathway.
AB  - FK506 binding protein 5 (FKBP5) belongs to a family of immunophilins named for
      their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis
      trans isomerases, and also with chaperones to help protein folding. Using glioma
      cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors.
      This finding was further validated by real-time reverse transcription-polymerase
      chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were
      then examined. We found that cell growth was suppressed after FKBP5 expression
      was inhibited by short interfering RNA transfection and enhanced by FKBP5
      overexpression. Electrophoretic mobility shift assay showed that nuclear factor
      kappa B (NF-kappaB) and DNA binding was enhanced by FKBP5 overexpression. The
      expression level of I-kappa B alpha and phosphorylated NF-kappaB was regulated by
      the expression of FKBP5. These data suggest that FKBP5 is involved in NF-kappaB
      pathway activation in glioma cells. In addition, FKBP5 overexpression in
      rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment,
      whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were
      synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting
      that the FKBP5 regulates glioma cell response to rapamycin treatment. In
      conclusion, our study demonstrates that FKBP5 plays an important role in glioma
      growth and chemoresistance through regulating signal transduction of the NF
      kappaB pathway.

PMID- 18320069
TI  - CXCL5 promotes prostate cancer progression.
AB  - CXCL5 is a proangiogenic CXC-type chemokine that is an inflammatory mediator and
      a powerful attractant for granulocytic immune cells. Unlike many other
      chemokines, CXCL5 is secreted by both immune (neutrophil, monocyte, and
      macrophage) and nonimmune (epithelial, endothelial, and fibroblastic) cell types.
      The current study was intended to determine which of these cell types express
      CXCL5 in normal and malignant human prostatic tissues, whether expression levels
      correlated with malignancy and whether CXCL5 stimulated biologic effects
      consistent with a benign or malignant prostate epithelial phenotype. The results
      of these studies show that CXCL5 protein expression levels are concordant with
      prostate tumor progression, are highly associated with inflammatory infiltrate,
      and are frequently detected in the lumens of both benign and malignant prostate
      glands. Exogenous administration of CXCL5 stimulates cellular proliferation and
      gene transcription in both nontransformed and transformed prostate epithelial
      cells and induces highly aggressive prostate cancer cells to invade through
      synthetic basement membrane in vitro. These findings suggest that the
      inflammatory mediator, CXCL5, may play multiple roles in the etiology of both
      benign and malignant proliferative diseases in the prostate.

PMID- 18320070
TI  - DNA repair gene polymorphisms may be associated with prognosis of upper urinary
      tract transitional cell carcinoma.
AB  - Upper urinary tract transitional cell carcinoma (UUT-TCC) is quite an uncommon
      disease, and its prognosis differs among individuals irrespective of tumor stage.
      DNA repair gene polymorphisms are reported to result in the modulation of the
      repair capacity and might influence the prognosis of UUT-TCC. We examined the
      associations between functional polymorphisms in five DNA repair genes, and the
      prognosis of UUT-TCC in 103 UUT-TCC patients. Variant alleles in xeroderma
      pigmentosum complementation group C, more than three total variant alleles in all
      DNA repair genes studied and more than two total variant alleles in three
      nucleotide excision repair genes were independently associated with improved
      overall and disease-specific survival of UUT-TCC patients in multivariate
      analysis (P = .0063 and P = .0005 for xeroderma pigmentosum complementation group
      C, P = .016 and P = .0016 for all genes, and P = .0053 and P = .018 for
      nucleotide excision repair genes, respectively). These results suggest that some
      DNA repair gene polymorphisms may preoperatively be valuable as prognostic
      factors for UUT-TCC beyond tumor stage and grade, helping to provide optimal
      treatment strategies for individual patients.

PMID- 18320071
TI  - Pharmacological inhibition of DNA methylation induces proinvasive and
      prometastatic genes in vitro and in vivo.
AB  - The mechanism of action of DNA methylation inhibitor 5-aza-2'-deoxycytidine (5
      aza-CdR), a potential anticancer agent is believed to be activated by the
      demethylation of tumor suppressor genes. We tested here the hypothesis that
      demethylating agents also demethylate and activate genes involved in invasion and
      metastasis and therefore might increase the risk of developing tumor metastasis.
      The effect of 5-aza-CdR on noninvasive human breast cancer cells MCF-7 and ZR-75
      1 was evaluated by cell proliferation, invasion, and migration assay. The ability
      of 5-aza-CdR to activate a panel of silenced prometastatic and tumor suppressor
      genes was evaluated using reverse transcription-polymerase chain reaction and
      bisulfite DNA sequence analysis in vitro and for change in tumor growth and gene
      expression in vivo. Treatment of MCF-7 and ZR-75-1 with 5-aza-CdR diminished cell
      proliferation, induced tumor suppressor RASSF1A, and altered cell cycle kinetics'
      G(2)/M-phase cell cycle arrest. While these effects of 5-aza-CdR slowed the
      growth of tumors in nude mice, it also induced a battery of prometastatic genes,
      namely, uPA, CXCR4, HEPARANASE, SYNUCLEIN gamma, and transforming growth factor
      beta (TGF-beta), by demethylation of their promoters. These results draw
      attention to the critical role of demethylation as a potential mechanism that can
      promote the development and progression of tumor metastasis after demethylation
      therapy as an anticancer treatment.

PMID- 18320072
TI  - Differential expression of secretory phospholipases A2 in normal and malignant
      prostate cell lines: regulation by cytokines, cell signaling pathways, and
      epigenetic mechanisms.
AB  - Upregulation of group IIA phospholipase A(2) (sPLA(2)-IIA) correlates with
      prostate tumor progression suggesting prooncogenic properties of this protein.
      Here, we report data on expression of three different sPLA(2) isozymes (groups
      IIA, V, and X) in normal (PrEC) and malignant (DU-145, PC-3, and LNCaP) human
      prostate cell lines. All studied cell lines constitutively expressed sPLA(2)-X,
      whereas sPLA(2)-V transcripts were identified only in malignant cells. In
      contrast, no expression of sPLA(2)-IIA was found in PrEC and DU-145 cells, but it
      was constitutively expressed by IFN-gamma in LNCaP and PC-3 cells. Expression of
      sPLA(2)-IIA is upregulated in PC-3 and in PrEC cell in a signal transducer and
      activator of transcription-1-dependent manner, but not in LNCaP cell. Additional
      signaling pathways regulating sPLA(2)-IIA expression include cAMP/protein kinase
      A, p38 mitogen-activated protein kinase, protein kinase C, Rho-kinase, and
      mitogen-activated/extracellular response protein kinase / extracellular signal
      regulated kinase. No deletions were revealed in the sPLA(2)-IIA gene from DU-145
      cells lacking the expression of sPLA(2)-IIA. Reexpression of sPLA(2)-IIA was
      induced by 5-aza-2'-deoxycytidine demonstrating that DNA methylation is
      implicated in the regulation of sPLA(2)-II. Together, these data suggest that
      sPLA(2)-IIA and sPLA(2)-V, but not sPLA(2)-X, are differentially expressed in
      normal and malignant prostate cells under the control of proinflammatory
      cytokines; epigenetic mechanisms appear involved in the regulation of sPLA(2)-IIA
      expression, at least in DU-145 cells.

PMID- 18320073
TI  - Inhibition of JAK1, 2/STAT3 signaling induces apoptosis, cell cycle arrest, and
      reduces tumor cell invasion in colorectal cancer cells.
AB  - Abnormalities in the STAT3 pathway are involved in the oncogenesis of several
      cancers. However, the mechanism by which dysregulated STAT3 signaling contributes
      to the progression of human colorectal cancer (CRC) has not been elucidated, nor
      has the role of JAK, the physiological activator of STAT3, been evaluated. To
      investigate the role of both JAK and STAT3 in CRC progression, we inhibited JAK
      with AG490 and depleted STAT3 with a SiRNA. Our results demonstrate that STAT3
      and both JAK1 and 2 are involved in CRC cell growth, survival, invasion, and
      migration through regulation of gene expression, such as Bcl-2, p1(6ink4a),
      p21(waf1/cip1), p27(kip1), E-cadherin, VEGF, and MMPs. Importantly, the FAK is
      not required for STAT3-mediated regulation, but does function downstream of JAK.
      In addition, our data show that proteasome-mediated proteolysis promotes
      dephosphorylation of the JAK2, and consequently, negatively regulates STAT3
      signaling in CRC. Moreover, immunohistochemical staining reveals that nuclear
      staining of phospho-STAT3 mostly presents in adenomas and adenocarcinomas, and a
      positive correlation is found between phospho-JAK2 immunoreactivity and the
      differentiation of colorectal adenocarcinomas. Therefore, our findings illustrate
      the biologic significance of JAK1, 2/STAT3 signaling in CRC progression and
      provide novel evidence that the JAK/STAT3 pathway may be a new potential target
      for therapy of CRC.

PMID- 18320074
TI  - EML4-ALK fusion lung cancer: a rare acquired event.
AB  - A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung
      cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of
      adenocarcinomas of the lung were independently reported recently. Because the
      EML4-ALK fusion was only shown by a reverse transcription-polymerase chain
      reaction approach, we developed fluorescent in situ hybridization assays to
      interrogate more than 600 NSCLCs using break-apart probes for EML4 and ALK. We
      found that EML4-ALK fusions occur in less than 3% of NSCLC samples and that EML4
      and/or ALK amplifications also occur. We also observed that, in most cases in
      which an EML4/ALK alteration is detected, not all of the tumor cells harbor the
      lesion. By using a detailed multi-fluorescent in situ hybridization probe assay
      and reverse transcription-polymerase chain reaction, we have evidence that other,
      more common mechanisms besides gene inversion exist including the possibility of
      other fusion partners for ALK and EML4. Furthermore, we confirmed the NKX2-1 high
      level amplification in a significant subset of NSCLC and found this amplification
      to be mutually exclusive to ALK and EML4 rearrangements.

PMID- 18320075
TI  - Homologues of HSV-1 nuclear egress factor UL34 are potential phosphoinositide
      binding proteins.
AB  - During the herpesvirus replication cycle, viral transcription, DNA replication,
      formation of capsids and DNA packaging occur in the nucleus. The subsequent
      nuclear egress of newly synthesized nucleocapsids is performed by budding of the
      inner leaflet of the nuclear membrane, which creates the primary envelope.
      Although products of two genes conserved throughout the Herpesviridae family (HSV
      1 UL34 and UL31) have previously been shown to be involved in the execution of
      this process, the molecular basis of their activity is not clear. Here we present
      results of protein structure prediction for the conserved domain of UL34. The
      applied methodology suggests that this protein adopts a pleckstrin homology (PH)
      fold to perform its function. A detailed inspection of the ligand binding site
      strongly supports the hypothesis that UL34 orthologs can recognize
      phosphoinositides. Since previous works suggest that alterations of UL34 gene
      product result in a drastic impairment of primary envelopment of HSV-1 and
      trapping of capsids in the nucleus, the presented data may lead to the
      development of novel anti-herpetic therapeutic strategies where analogs of
      phosphoinositides are administered.

PMID- 18320076
TI  - Cytomegalovirus immediate early gene UL37 encodes a novel MHC-like protein.
AB  - The cytomegalovirus (CMV) genome encodes four clusters of genes expressed
      immediately after infection--i.e.: UL36-38, UL122-123, TRS1-IRS1, and US3. The
      general function of these genes is associated with inhibition of cellular
      mechanisms of antiviral response. Although several biological processes have been
      mapped onto specific gene products, the knowledge of the molecular mechanism of
      their activity remains fragmentary. Here, we report the application of protein
      structure prediction methods in assigning the function to a glycosylated domain
      encoded by UL37 of CMV (gpUL37, UL37x3). The discerned similarity clearly points
      out that this domain represents a novel type of a major histocompatibility
      complex (MHC)-like protein, and consequently may play a central role in an
      additional mechanism of escape from antiviral response.

PMID- 18320078
TI  - Show me the data.

PMID- 18320079
TI  - Prevalence and covariates of electrocardiographic left ventricular hypertrophy in
      diabetic patients in Tanzania.
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) has been demonstrated to be a
      powerful predictor of cardiovascular (CV) morbidity and mortality in diabetic as
      well as hypertensive patients. However, less is known about the prevalence of
      electrocardiographic LVH (ECG-LVH) and its relation to other CV risk factors in
      diabetic patients in sub-Saharan Africa. Therefore, the aim was to assess the
      prevalence of ECG-LVH in diabetic patients in Dares Salaam, Tanzania, and its
      relation to other cardiovascular risk factors. METHODS: Two hundred and thirty
      seven consecutive patients attending the Muhimbili diabetic clinic were studied.
      ECG-LVH was diagnosed by Sokolow-Lyon voltage and Cornell voltage-duration
      product criteria. Q waves, ST-segment deviation, T-wave abnormalities and
      intraventricular conduction defects were classified by the Minnesota codes. Blood
      pressure (BP), serum creatinine, cholesterol and triglyceride levels, and HbA 1c
      and urinary albumin and creatinine concentrations were determined. RESULTS: The
      prevalence of LVH in patients was 16% by either ECG criteria; 12.2% by Sokolow
      Lyon and 5.1% by Cornell product criteria. Patients with LVH had significantly
      higher systolic and mean BP and pulse pressure, and a higher prevalence of ST
      segment abnormalities, T-wave inversion and albuminuria than those without LVH
      (all p < 0.05). In multivariate logistic regression analysis, systolic BP was the
      only independent predictor of ECG-LVH. The prevalence of ECG-LVH increased by 15%
      per 10 mmHg higher systolic BP [OR 1.151 (95% CI 1.009-1.314), p < 0.05].
      Clustering of cardiovascular risk factors differed significantly between type 1
      and type 2 diabetes patients. On average, type 1 patients had 0.8 and type 2 had
      2.2 additional CV risk factors. CONCLUSION: ECG-LVH was present in 16% of
      diabetic patients in Tanzania. Systolic BP was the most important predictor of
      ECG-LVH. Clustering of CV risks was significantly higher in type 2 than in type 1
      diabetics, demonstrating the need for systematic multiple risk-factor assessment
      in these patients.

PMID- 18320080
TI  - The alpha 2C Del322-325 adrenergic receptor polymorphism is not associated with
      heart failure due to idiopathic dilated cardiomyopathy in black Africans.
AB  - BACKGROUND: A four-amino acid deletion was identified within the alpha 2C
      adrenergic receptor (alpha 2C Del322-325) that, when homozygous, increases the
      risk of heart failure in African-Americans nearly six-fold. We hypothesised that
      homozygosity for the alpha 2C Del322-325 polymorphism may be a risk factor for
      heart failure due to idiopathic dilated cardiomyopathy (DCM) in black South
      Africans. METHODS: The alpha 2C Del322-325 polymorphism was genotyped in 37
      patients with heart failure and 34 controls, all of black African ancestry.
      Genotyping was performed by a size-fractionation assay. RESULTS: The patients
      studied ranged in age from 21 to 79 years with a mean age of 50 years, and 62%
      were male. No significant difference was observed in homozygosity for the alpha
      2C Del322-325 polymorphism or in allele and genotype frequencies between patients
      and controls. The frequency of the allele containing the deletion was 0.54 in
      cases and 0.53 in controls. The genotype frequencies in the patients were
      consistent with those of the controls (p = 0.56). CONCLUSIONS: Homozygosity for
      the alpha 2C Del322-325 polymorphism is not associated with an increased risk for
      heart failure due to idiopathic DCM in black South Africans.

PMID- 18320081
TI  - Short- and long-term outcomes of percutaneous coronary intervention in patients
      with low, intermediate and high ejection fraction.
AB  - BACKGROUND: Reduced ejection fraction (EF) has previously been shown to be a risk
      factor for adverse outcomes in patients undergoing percutaneous coronary
      intervention (PCI). However, with the advent of stents, procedural complications
      and restenosis rates have reduced dramatically. The aim of this study was to
      assess the association between left ventricular (LV ) ejection fraction and in
      hospital and longterm outcomes using a prospective registry. METHODS: After
      exclusion of patients with acute myocardial infarction (MI) and those with
      missing data on left ventricular ejection fraction, 2 030 patients undergoing PCI
      between March 2002 and 2004 remained in our prospective registry. Patients were
      divided into three categories: group 1: EF <or= 40% (n = 293), group 2: EF = 41
      49% (n = 268) and group 3: EF >or= 50% (n = 1 469). The frequency of in-hospital
      and follow-up outcomes between groups was compared using appropriate statistical
      methods. RESULTS: Stents were used for over 85% of the patients in each group.
      The mean EF +/- SD in the lowest to highest EF groups was 35.8 +/- 5.4%, 45.5 +/-
      1.6% and 57 +/- 5.7%, respectively. The angiographic and procedural success rates
      were 91.8, 92.1 and 94.1%, (p = 0.16); and 91.1, 90.3 and 92.9%, (p = 0.09),
      respectively. The respective cumulative major adverse cardiac events (MACE) and
      cardiac death rates at follow-up were 5.8, 2.2 and 3.3% (p = 0.04) and 2, 0.4 and
      0.3% (p = 0.02), respectively. The hazards ratio (95% CI) for MACE and cardiac
      death in the lowest versus highest EF groups were 2.07 (1.03-4.16) and 5.49 (1.29
      23.3). CONCLUSIONS: Patients with significant left ventricular dysfunction had
      higher long-term major adverse cardiac events and cardiac death rates. Even the
      use of newer techniques such as stenting did not compensate for this.

PMID- 18320082
TI  - Electrocardiographic abnormalities in patients with heart failure.
AB  - BACKGROUND: The morbidity and mortality from heart failure (HF) differ between
      patients with reduced (< 50%) and with preserved ( >or= 50%) left ventricular
      ejection fraction (LVEF) on account of many factors, including abnormalities
      detected in the electrocardiogram (ECG). The aim of this study was to determine
      and compare the ECG abnormalities between HF patients with reduced and with
      preserved LVEF. METHODS: The study was cross-sectional in design and carried out
      in Aminu Kano teaching hospital and Murtala Mohammed specialist hospital, Kano,
      Nigeria, from April 2005 to June 2006. We studied the resting electrocardiograms
      of all HF patients aged 15 years and older who were referred to the two centres
      for echocardiography. RESULTS: A total of 113 patients were studied and 98.2% of
      them had abnormal ECGs. Forty-two patients (37.2%) had preserved LVEF while the
      remaining 71 (62.8%) had reduced LVEF. Left ventricular hypertrophy (LVH) was the
      commonest ECG abnormality, found among 55 patients (77.5%) with reduced LVEF, and
      21 patients (50%) with preserved LVEF (p = 0.0026). The commonest arrhythmia was
      atrial fibrillation, found among 10 patients (14.1%) with reduced LVEF and eight
      patients (19.1%) with preserved LVEF (p = 0.486). Prolonged corrected QT interval
      was found among 30 (71.4%) and 56 patients (78.9%) with preserved and reduced
      LVEF, respectively (p 5 0.370). CONCLUSION: Most of the patients with heart
      failure studied in Kano, Nigeria had abnormal electrocardiograms, and the most
      common abnormality was LVH.

PMID- 18320083
TI  - Primary cardiac angiosarcoma with right coronary-to-right atrium fistula.
AB  - Primary tumours of the heart are rare. About 25% of all cardiac tumours are
      malignant and the most common of these is the angiosarcoma. We present a 61-year
      old male with a right atrial angiosarcoma that was detected on coronary
      angiography. The tumour showed marked vascularity and a right coronary-to-right
      atrium fistula, and the patient underwent surgical resection. Pathological
      examination of the tumour was consistent with a cardiac angiosacoma and the
      diagnosis was also confirmed by immuno-histochemistry. He consequently underwent
      chemotherapy, however the patient died 60 days after the surgery.

PMID- 18320084
TI  - Resolution of a giant atrial thrombus following anticoagulation therapy.
AB  - We report on a patient in whom a giant thrombus in the left atrium was detected
      by transthoracic echocardiography. Anticoagulant theraphy was started. After two
      months of therapy, repeat echocardiography showed complete resolution of the
      thrombus. This case indicates that large and presumably organised thrombi may be
      treated with anticoagulant therapy.

PMID- 18320085
TI  - William Nelson ECG quiz.

PMID- 18320086
TI  - Pacemaker-mediated tachycardia induced by left ventriculography during diagnostic
      catheterisation: a rare event.
AB  - Pacemaker-mediated tachycardia (PMT) is an arrhythmia seen in patients implanted
      with dual-chamber pacemakers. It occurs when ventricular contraction is followed
      by retrograde conduction to the atrium, which is sensed by the pacemaker, leading
      to ventricular triggering. A vicious re-entry cycle is set up, leading to
      incessant tachycardia unless appropriately terminated. A common precipitant is a
      premature ventricular contraction (PVC). Although PVCs are frequently generated
      during ventriculography, PMT is an extremely rare event during cardiac
      catheterisation despite the fact that a large number of patients with implanted
      pacemakers do undergo the procedure. We report on a case and hope to highlight
      the possibility of PMT occurring during catheterisation, as well on therapeutic
      options.

PMID- 18320087
TI  - Takotsubo cardiomyopathy: an acute and reversible cardiomyopathy mimicking acute
      myocardial infarction.
AB  - Takotsubo cardiomyopathy is an acute, reversible form of left ventricular
      dysfunction precipitated by emotional or physical stress. The condition is
      important to recognise as it mimics acute myocardial infarction and acute
      coronary syndrome. Most patients are female and postmenopausal. Presenting
      symptoms include severe chest pain, acute dyspnoea, hypotension or even
      cardiogenic shock. The ECG changes are suggestive of an acute coronary syndrome
      with T-wave inversion with/without ST elevation, most often in the precordial
      leads. The syndrome is characterised by a sudden onset of transient extensive
      akinesia of the left ventricle, often involving all three major coronary artery
      territories, in the absence of significant coronary artery stenosis. The wall
      motion typically involves the apex of the left ventricle with hyperkinesis of the
      base of the heart. Variant forms have recently been described where the wall
      motion abnormality involves the mid-ventricular wall with hyperkinesis of the
      base and apex, or the base of the heart with hyperkinesis of the apex.
      Characteristically, there is only a limited release of cardiac enzymes
      disproportionate to the extent of regional wall motion abnormality. Transient
      right ventricular dysfunction may occur and is associated with more
      complications, longer hospitalisation and worse left ventricular systolic
      dysfunction. Serial echocardiography is useful to document improvement in cardiac
      function. The pathogenesis is unclear. Transient mid-cavity obstruction has been
      invoked with subsequent myocardial stunning in the akinetic segments. Treatment
      is supportive. The most effective long-term management remains to be defined.
      Although the prognosis is good with recovery of ventricular function at about
      three weeks, some patients have died. The syndrome may recur.

PMID- 18320088
TI  - Electrocardiographic left ventricular hypertrophy with strain pattern:
      prevalence, mechanisms and prognostic implications.
AB  - BACKGROUND: Electrocardiographic left ventricular hypertrophy with strain pattern
      has been documented as a marker for left ventricular hypertrophy. Its presence on
      the ECG of hypertensive patients is associated with a poor prognosis. This review
      was undertaken to report the prevalence, mechanism and prognostic implications of
      this ECG abnormality. MATERIALS AND METHODS: We conducted a comprehensive search
      of electronic databases to identify studies relating to the title of this review.
      The search criteria were related to the title. Two of the reviewers independently
      screened the searches. RESULTS: Results were described qualitatively. The data
      were not pooled because there were no randomised studies on the topic. The
      prevalence of ECG strain pattern ranged from 2.1 to 36%. The highest prevalence
      was reported before the era of good antihypertensive therapy. The sensitivity as
      a measure of left ventricular hypertrophy ranged from 3.8 to 50%, while the
      specificity was in the range of 89.8 to 100%. Strain pattern was associated with
      adverse cardiovascular risk factors as well as increased all-cause and CV
      morbidity and mortality. ST-segment depression and T-wave inversion on the ECG
      was recognised as the strongest marker of morbidity and mortality when ECG-LVH
      criteria were utilised for risk stratification in hypertensive subjects.
      CONCLUSION: Electrocardiographic strain pattern identifies cardiac patients at
      higher risk of cardiovascular-related as well as all-cause morbidity and
      mortality.

PMID- 18320089
TI  - ONTARGET programme of cardio- and vascular protection - first results are
      imminent.

PMID- 18320090
TI  - Extended ASCOT - lipid lowering (ASCOT-LLA) study shows positive results of
      atorvastatin.

PMID- 18320092
TI  - Controlled off-label use of recombinant activated factor VII (NovoSeven) can
      build evidence base.

PMID- 18320093
TI  - A practical routine regimen for amiodarone usage to reduce atrial fibrillation in
      patients undergoing coronary bypass surgery.

PMID- 18320094
TI  - Managing acutely ill medical patients to reduce venous thromboembolic events.

PMID- 18320095
TI  - SA experts comment on clopidogrel and aspirin (dual platelet therapy) use with
      bare metal and drug-eluting stents.

PMID- 18320096
TI  - First head-to-head study comparing rosuvastatin and atorvastatin effects on the
      treatment of atherosclerosis.

PMID- 18320097
TI  - [Fever that should not kill].

PMID- 18320098
TI  - [Diagnosis of small intestinal bacterial overgrowth in children: the use of
      lactulose in the breath hydrogen test as a screening test].
AB  - INTRODUCTION: The standard method for diagnosis of small intestinal bacterial
      overgrowth is a duodenal aspirate that produces a coliform count greater than
      10(5) colonic forming units/ml. Because this is an invasive procedure, the
      lactulose breath hydrogen test is considered as a non-invasive alternative.
      Better experimental support is required, however, for the routine use of
      lactulose in diagnosis. OBJECTIVE: Experimental evidence is provided to support
      the use of lactulose in the breath hydrogen test. Validation of the test is
      accomplished by comparison to the duodenal aspirate culture. MATERIALS AND
      METHODS: A rational basis for the use of lactulose was established by a
      comparison of the kinetics of lactulose and lactose on intestinal lactase. For
      validation, the hydrogen test was applied to 47 children suffering from
      gastrointestinal disorders, and the results compared with aspirate culture
      counts. The validity of the hydrogen test was assessed by a contingency table and
      the degree of agreement established by the kappa index. RESULTS: The kinetics
      data showed that lactase is 240 times less efficient in presence of lactulose
      than it is in presence of lactose. The sensitivity of the breath hydrogen test
      was 85.7% (82.0-89.4%), its specificity 90.9% (89.3-92.5%), the predictive
      positive value 80.0% (76.5-83.5%) and the predictive negative value 93.8% (92.1
      95.4%); the kappa index=0.785 (0.54-0.95) showed excellent agreement between the
      two diagnostic tests. CONCLUSION: The results provided experimental support for
      the use of lactulose in the breath hydrogen test, and it was validated as
      screening test in the diagnosis of small intestinal bacterial overgrowth.

PMID- 18320099
TI  - [A global view of population health in Colombia: role of social macro
      determinants].
AB  - INTRODUCTION: The social environment is an important determinant of population
      and individual health. However, its impact is often not considered in national
      health policies and generally its attributes are considered as constants. For
      this reason, contemporary health policies place greater emphasis on individual
      risk factors. OBJECTIVE: Colombias position in the world ranking is described
      with respect to several social macro-determinants of health, previously
      characterized as components of class/welfare regime model. MATERIALS AND METHODS:
      The exploratory study included all countries with comparable data including the
      following: (1) economic development [gross domestic product per capita adjusted
      for purchasing power parity], (2) income inequality [Gini coefficient], (3)
      social capital corruption perceptions index and generalized trust, and (4)
      political regime index of freedom. First, correlations between these macro
      determinants were estimated, and second, the relationship between them and life
      expectancy at birth was explored. Finally, the position of Colombia in global
      context was determined. RESULTS: Important correlations occurred among the macro
      determinants. Colombia tended to have intermediate to low positions in the global
      context in all macro-determinants, with the exception of gross domestic product
      per capita adjusted for purchasing power parity. CONCLUSION: The macro
      determinant of population health with the highest potential of effecting
      improvement in health conditions is to modify income inequality.

PMID- 18320100
TI  - [Giardia duodenalis prevalence and associated risk factors in preschool and
      school-age children of rural Colombia].
AB  - INTRODUCTION: Giardia doudenalis infection remains an important public health
      problem worldwide, as well as in Colombia. This infection is associated with
      poverty and lack of public services. OBJECTIVE: The study was designed to
      describe prevalence trends of Giardia duodenalis infections in preschool and
      school-age children from the village of La Virgen, Quipile, Cundinamarca, and its
      possible association with socioeconomic variables. MATERIALS AND METHODS: Three
      cross-sectional studies were undertaken in 1995, 2001 and 2005. In each, a non
      random sample was selected among children aged <1 to 15 years. Fecal samples were
      collected for direct examination in order to determine G. duodenalis infection
      and other intestinal parasites. During the 2005 survey information was collected
      concerning the sociodemographic and economic conditions in each family group from
      which a child was sampled. RESULTS: The prevalence of G. duodenalis infection did
      not change significantly during the study period-13.6% in 1995, 12.8% in 2001 and
      15.2% in 2005. These results suggested that belonging to the subsidized health
      care regime was associated with G. duodenalis infection (prevalence rate [PR]:
      4.47; 95% confidence interval [95% CI] 0.6-32.0), not having water supply (PR
      2.6; 95% CI 1.1-6.0) and involvement in agricultural activities (PR 2.5; 95% CI
      1.0-6.4). CONCLUSION: Giardiasis is a continuing public health problem at La
      Virgen. As long as the environmental and socioeconomic factors associated with
      infection persist, this intestinal protozoan infection will not be controlled.

PMID- 18320101
TI  - [Trends in adult mortality in the city of Medellin, Colombia, 1994-2003].
AB  - INTRODUCTION: The death of an adult affects the family as well as the adults role
      in its labor and social environment. In developing countries, the load of
      diseases and associated trauma continues to increase and place increasing demands
      for the intervention by public health authorities. OBJECTIVE: Trends of mortality
      were determined for adults of 20 to 64 years in Medellin, Colombia, between 1994
      and 2003 according to sex. MATERIALS AND METHODS: A retrospective, longitudinal
      study was undertaken that analyzed trends in mortality rates. A secondary data
      source consisted of death certificates recorded at the Departamento
      Administrativo Nacional de Estadisticas (National Department of Statistics)
      during the decade 1994-2003. RESULTS: The rate average of mortality for the
      decade was 497 deaths per 1000 habitants. Men displayed a risk of dying of 3.5
      (95%CI: 2.0-6.0) times that of women. Approximately 59% of the deaths had
      external causes (i.e., not related to illness or old age). Twenty-nine percent of
      the female deaths were due to tumors; this trend was positive throughout the
      decade. The 5 most important causes of mortality were as follows: aggressive
      behaviors, heart disease, traffic accidents, malignant tumors and pulmonary
      disease. The trend in deaths due to by external causes was negative, but positive
      for the deaths due to acute myocardial infarctions (mainly in the 45 to 64 year
      population) and HIV in young adults. An increasing trend in malignant breast
      cancer was observed in young adult women, but remained constant in the 45 to 64
      year-old female population. CONCLUSION: Mortality in the adult population differs
      by sex and age. The younger male population is more at risk than women as a
      consequence of environmental factors in early life. In later life, women are more
      strongly affected by increasing incidence of cardiovascular disease and malignant
      tumors. The increased levels of mortality at all age levels represent a problem
      that generates a high human and economic cost.

PMID- 18320102
TI  - Rickettsial infection in capybaras (Hydrochoerus hydrochaeris) from Sao Paulo,
      Brazil: serological evidence for infection by Rickettsia bellii and Rickettsia
      parkeri.
AB  - INTRODUCTION: In Brazil, capybaras (Hydrochoerus hydrochaeris) are important
      hosts for Amblyomma ticks, which in turn can transmit rickettsiae to humans and
      animals. Therefore, capybaras are potential sentinels for rickettsial infection.
      OBJECTIVE: The present study evaluated rickettsial infection in capybaras in
      different areas of the state of Sao Paulo, where rickettsiosis has never been
      reported. Materials and methods. Blood sera from 73 capybaras from six localities
      in Sao Paulo were tested by indirect immunofluorescence assay using Rickettsia
      rickettsii, Rickettsia parkeri, and Rickettsia bellii antigens. Capybara spleens
      were tested by PCR, targeting a fragment of the rickettsial gltA gene. Ticks were
      collected from each capybara sample and taxonomically identified to species.
      RESULTS: A total of 94 positively reacting capybara samples, 19 (26.0%), 25
      (34.2%), and 50 (68.5%) capybara sera reacted to R. rickettsii, R. parkeri, and
      R. bellii, respectively. Twenty-five capybara sera showed titers to R. bellii at
      least four-fold higher than to any of the other two antigens. These sera were
      considered homologous to R. bellii. Using the same criteria, 3 capybara sera were
      considered homologous to R. parkeri. No sera were be considered homologous to R.
      rickettsii. No rickettsial DNA was detected in capybara spleen samples. Ticks
      collected on capybaras were Amblyomma dubitatum and Amblyomma cajennense.
      CONCLUSIONS: The first evidence is reported of R. bellii natural infection in
      vertebrate hosts, and the first evidence of R. parkeri infection in capybaras.
      While R. parkeri is known to infect and cause disease in humans, no similar
      evidence for human infection has been indicated by R. bellii.

PMID- 18320103
TI  - [Evaluation of amyloid-beta by the E280A mutation in presenilin gene].
AB  - INTRODUCTION: The E280A mutation of the presenilin 1 gene has been found to be
      the most common associate in Alzheimers patients with a family history of this
      disease. Presenilin 1 is a critical component of the g-secretase complex and
      plays an essential role in the production of amyloid-beta peptide. This peptide
      has been strongly associated with the physiopathology of the disease. OBJECTIVE:
      The E280A mutation in the presenilin 1 was investigated for increased production
      of amyloid-beta , as a response to gain in gamma-secretase function. MATERIALS
      AND METHODS: Levels of systemic amyloid-beta were measured with congo red
      staining and immuno-histochemistry of the tissues of affected cadavers, compared
      with non-affected cadavers. The 40 and 42 amino acid amyloid-beta levels were
      quantified by ELISA assay in CHO cell cultures. The amyloid precursor protein
      expressed by the cultures was detected by transfection with the cDNAs of
      presenilin 1 carrying the M146L, E280A, DE9 y L392V mutations. RESULTS: Protein
      deposits were found in all tissues investigatged, but only a few with beta 
      amyloid deposition. No differences were observed in the amount or location of
      amyloid-beta between affected and unaffected cadavers. Not increase was noted in
      the production of amyloid-beta from the CHO cells transfected with cDNA from any
      of the mutations of presenilin 1. CONCLUSIONS: The E280A mutation in the
      presenilin 1 gene was not associated with the increased production of amyloid
      beta in non-neuronal peripheral tissues, or in the in vitro model. This is in
      contrast to the expectation in a gamma-secretase gain of function.

PMID- 18320104
TI  - [Lipid and apoprotein A-I and B-100 levels in school children school from five
      central-eastern provinces of Colombia].
AB  - INTRODUCTION: Lipid and apolipoprotein are known to vary in children.These
      variations can be associated to physiologic changes or the environment; this last
      one probably induces future alterations in the lipids. OBJECTIVE: The levels of
      total cholesterol, LDL-cholesterol, HDL-cholesterol, and apoproteins A-I and B
      100 were compared in school children from five provinces of middle-eastern
      Colombia. Associations were made with age, gender, body mass index, fitness
      activity, and food preference. MATERIALS AND METHODS: 741 blood samples were
      collected and biochemical determinations were undertaken with standard enzymatic,
      colorimetric, and inmunoturbidimetric methods. All values are presented as mean
      +/- SE, comparisons among groups were made using Student s t test, ANOVA and
      Scheffe. RESULTS: Lipid variation was observed in the school children, however in
      contrast, the concentrations of Apoproteins ApoB-100 and ApoA-I tended to be
      constant. The lipid fluctuations showed some relationship with changes in age and
      gender, however, changes were also observed that indicate a possible relationship
      with sexual maturation, diet and fitness activity. An important finding was that
      the HDL cholesterol value was lower that reported from other countries, while the
      triglycerides was higher and this may indicate a future increased risk for
      cardiovascular diseases. CONCLUSION: Fluctuations occur in the lipid levels and
      vary with age and gender. Associations with other factors may be present;
      however, more research is necessary to determinate the contribution of each
      factor. A promotion campaign among school-age children for a healthier life style
      may contribute to a decrease in future risk for cardiovascular diseases
      associated with low HDL-cholesterol levels and higher triglycerides.

PMID- 18320105
TI  - [Organophosphorus and carbamate pesticide exposure in Putumayo Province,
      Colombia].
AB  - INTRODUCTION: In 2005, the Sistema de Vigilancia en Salud Publica, the
      governmental agency responsible for monitoring public health, found that Putumayo
      Province has the highest incidence of poisoning by pesticides in Colombia.
      OBJECTIVE: Exposure to organophosphorus and carbamate pesticides and carbamates
      was established in the agricultural population of Putumayo by determining
      acetylcholinesterase levels. MATERIALS AND METHODS: A cross-sectional survey was
      made in 204 occupationally exposed workers in four municipalities of Putumayo. A
      questionnaire was administered to collect subject information; a blood sample was
      taken for acetylcholinesterase determination by Michels method. A straightforward
      analysis of the variables and possible associations were explored. A group of
      workers was enabled with SARAR (a participative educational strategy that means:
      S: safety, A: association, R: reaction, A: actualization and R:
      responsability)methodology for use and handling of pesticides. RESULTS: The
      average time of exposure was nine years. Seventy-five percent declared using
      extremely toxic pesticides and 13% highly toxic. On average, they applied
      pesticides 7.3 hours/day. Nearly 10% used organochloride pesticides. Furthermore,
      17.6% demonstrated inhibition of the enzyme acetylcholinesterase. CONCLUSION: A
      realistic scale of the pesticide use problem in humans was obtained; and the data
      effectively recommend an educatiional intervention for the workers and their
      families with SARAR methodology.

PMID- 18320106
TI  - [The intergenic region of the histone H2a gene supports two major lineages of
      Trypanosoma rangeli].
AB  - INTRODUCTION: Trypanosoma rangeli has been classified in the KP1(+) and KP1(-)
      subpopulations, based on the mini-exon gene and kinetoplast DNA minicircle
      amplification profiles. OBJECTIVE: The intergenic region of the histone h2a gene
      was compared between KP1(+) and KP1(-) strains of T. rangeli to substantiate this
      classification. MATERIALS AND METHODS: The amplification, cloning and sequencing
      of the h2a gene intergenic region was undertaken for the Tre and 5048 KP1(-)
      strains for comparison with the Choachi KP1(+) strain. These sequences, along
      with those previously reported for the KP1 (+) and KP1 (-) H14 and C23 strains,
      were used to reconstruct phylogenetic trees based on the "neighbor-joining",
      maximum parsimony and maximum likelihood methods. The Y strain of Trypanosoma
      cruzi was chosen as the outgroup. RESULTS: Intra-specific heterogeneity was
      observed in the size of the gene region under study, supported by bootstarp
      values of 85% (neighbor-joining), 66% (maximum parsimony) and 57% (maximum
      likelihood). The KP1(-) strains were grouped apart, clearly differentiated from
      the KP1(+) strains. The latter demonstrated a higher intra-specific
      heterogeneity, both in sequence length and composition. In addition, a closer
      phylogenetic relationship between T. rangeli and T. cruzi was found to be more
      closely related to one another than to T. rangeli and Trypanosoma brucei.
      CONCLUSION: Phylogenetic analyses of analyzed strains based on the intergenic
      region of the h2a genes supported the T. rangeli grouping in two major
      subpopulations known as KP1(+) and KP1(-) strains. However, a higher number of
      strains are needed to confirm this finding.

PMID- 18320107
TI  - [Evaluation of diagnostic scales for appendicitis in patients with lower
      abdominal pain].
AB  - INTRODUCTION: Diagnosis of apendicitis is difficult; however several clinical
      scales have been developed that attempt to improve diagnostic accuracy.
      OBJECTIVE: The operational characteristics of Alvarado and Fenyo scales were
      defined in patients with abdominal pain suggestive of appendicitis and were
      compare with clinical and pathological diagnoses. MATERIAL AND METHODS: A
      prospective trial assessed the diagnostic tests. Sign, symptoms, and laboratory
      tests were included in scales selected. Surgeon decision was maintained
      independent from the results of the scales. Sensitivity, specificity, positive
      and negative predictive value and positive and negative likelihood ratio for each
      scale was compared with the surgeon evaluation. RESULTS: The sample included 374
      patients with approximately equal sexes. Of these 269 patients underwent surgery.
      Howeve, 16.9% of the male and 31.4% of female patients did not have appendicitis.
      For men, a diagnosis made by the surgeon had better sensitivity than scales
      (86.2% vs. 73% for Alvarado and 67.2% for Fenyo) without significant differences
      in specificity. For women, surgeon and Alvarado scale diagnoses were similar, and
      better than Fenyo scale (77.1% vs. 79.5% for Alvarado and 47% for Fenyo), but
      specificity was higher for Fenyo scale (92.9% vs. 71.4% for Alvarado and 75.9%
      for surgeon). Accuracy in diagnosis of appendicitis increases with a higher
      Alvarado score. CONCLUSION: For men with abdominal pain on right lower quadrant,
      surgeon diagnosis is more accurate than scales. For women, Fenyo scale offers a
      better sensitivity. Alvarado score can facilitate decision-making in patients
      with these abdominal symptoms.

PMID- 18320108
TI  - [Analysis of the primary and secondary structure of the mitochondrial serine
      transfer RNA in seven species of Lutzomyia].
AB  - INTRODUCTION: Lutzomyia sand flies are involved in the transmission of the
      parasite Leishmania spp. in America. The taxonomy of these vectors is
      traditionally based on morphological features of the adult stage, particularly
      the paired structures of the head and genitalia. Although these characters are
      useful to distinguish most species of Lutzomyia, morphological identification may
      be complicated by the similarities within subgenera and species group. OBJECTIVE:
      To evaluate the utility of mitochondrial serine transfer RNA tRNA Ser for
      taxonomic identification of Lutzomyia. MATERIALS AND METHODS: Seven sand fly
      species, each representing one of the 27 taxonomic subdivisions in genus
      Lutzomyia, were analyzed including L. trinidadensis (Oswaldoi group), L.
      (Psychodopygus) panamensis, L.(Micropygomyia) cayennensis cayennensis, L.
      dubitans (Migonei group), L. (Lutzomyia) gomezi, L. rangeliana (ungrouped) and L.
      evansi (Verrucarum group). The mitochondrial tRNA Ser gene, flanked by the
      cytochrome b and NAD dehydrogenase subunit one genes, was extracted, amplified
      and sequenced from each specimen. Secondary structure of the tRNA Ser was
      predicted by comparisons with previously described homologous structures from
      other dipteran species. RESULTS: The tRNA Ser gene ranged in size from 66 base
      pairs in L. gomezi to 69 base pairs in L. trinidadensis. Fourteen polymorphic
      sites, including four insertion-deletion events, were observed in the aligned 70
      nucleotide positions. The majority of the substitutions were located in the
      dihydrouridine, ribothymidine-pseudouridine-cytosine and variable loops, as well
      as in the basal extreme of the anticodon arm. CONCLUSION: Changes of primary
      sequence of the tRNASer provided useful molecular characters for taxonomic
      identification of the sand fly species under consideration.

PMID- 18320109
TI  - [Molecular identification of non-tuberculous mycobacteria].
AB  - INTRODUCTION: Nontuberculous mycobacteria can be saprophytic, pathogenic or
      opportunistic. The most common diseases produced by these microorganisms are the
      post-surgical infections due to anesthetic procedures, infections associated with
      catheters, disseminated cutaneous diseases and pulmonary and central nervous
      system diseases that especially affect HIV patients. Identification of the
      nontuberculous mycobacteria can take several weeks and even then, differentiation
      of complex members is not possible. OBJECTIVE: The PCR-restriction analysis (PRA)
      technique was evaluated as a method for genotypic identification of
      nontuberculous mycobacteria isolated of clinical samples located in the culture
      collection of the Instituto Nacional de Salud (National Institute of Health),
      Bogota, Colombia. MATERIALS AND METHODS: Seventy clinical isolates of
      nontuberculous mycobacteria stored in 50% glycerol at -70 degrees C were
      identified by phenotypic techniques. The genotypic identification was made using
      the PCR-restriction analysis (PRA) using the restriction enzymes BstEII and
      HseIII, the restriction products were visualized on gels of agarose to 3%, and
      the concordance between the methodologies was evaluated. RESULTS: A matching of
      100% was obtained in the identification of Mycobacterium terrae, M. szulgai, M.
      avium, M. chelonae and M. scrofulaceum, the matching between M. fortuitum
      species, M. abscessus, M. gordonae and M. intracellulare varied from 44 to 89%;
      there was no concurrence in the identification of species M. flavescens and M.
      malmoense. CONCLUSIONS: PRA provided a fast, inexpensive and accurate alternative
      for the identification of nontuberculous mycobacteria that permited the
      differentiation among species of a complex and determining the subtype of each
      species sample.

PMID- 18320110
TI  - The direct agglutination test as an alternative method for the diagnosis of
      canine and human visceral leishmaniasis.
AB  - INTRODUCTION: Visceral leishmaniasis is the most severe clinical form of
      leishmaniasis and is often fatal without proper treatment. Therefore, early and
      accurate diagnosis is important, but often difficult in endemic areas. OBJECTIVE:
      The aim was to evaluate a direct agglutination test as a potential visceral
      leishmaniasis diagnostic method in endemic areas of Venezuela. MATERIALS AND
      METHODS: The performance of the direct agglutination test, based on freeze-dried
      Leishmania donovani antigen was evaluated under laboratory conditions using serum
      samples of humans and dogs from several Venezuelan visceral leishmaniasis endemic
      areas: Nueva Esparta (Margarita Island), Lara, Anzoategui and Trujillo Status.
      The study included confirmed visceral leishmaniasis patients (n=30), visceral
      leishmaniasis suspected subjects (n=4), healthy controls (n=19) and patients with
      other confirmed diseases (n=20). In addition, 24 serum samples from dogs with
      confirmed visceral leishmaniasis and 18 healthy control dogs were tested.
      RESULTS: All serum samples of visceral leishmaniasis patients, either active or
      recovered, were positive. They showed anti-L. donovani titers above 1:1600. Three
      out of four suspected visceral leishmaniasis cases were also positive, while
      serum samples from endemic controls and patients with other diseases had titers
      lower than 1:800. A sensitivity of 100% was obtained for all threshold levels
      under consideration and 100% specificity at the threshold titer of 1:800 (95%
      confidence interval: 91-100%). A 93% sensitivity (95% confidence interval: 76
      99%) was observed in dog samples, with 100% specificity (95% confidence interval:
      79-100%) at the threshold titer of 1:200. CONCLUSION: The direct agglutination
      test seems suitable for use in epidemiological studies and for serological
      diagnosis of human visceral leishmaniasis and canine visceral leishmaniasis.

PMID- 18320111
TI  - [Identification of Haemophilus influenzae, Streptococcus pneumoniae and Neisseria
      meningitidis by polymerase chain reaction].
AB  - INTRODUCTION: Haemophilus influenzae, Streptococcus pneumoniae and Neisseria
      meningitidis are the main human pathogens that cause meningitis. OBJECTIVE:
      Primers omp2, lytA and crgA were evaluated with H. influenzae, S. pnumoniae and
      N. meningitidis DNA in a multiplex PCR, determining the sensitivity and the
      specificity of the technique. MATERIALS AND METHODS: Primers for H. influenzae
      outer membrane protein (omp2, 1000 pb), S. pneumoniae autolysin (lytA, 395 pb)
      and N. meningitidis, contact regulated gene (crgA, 230 pb) were evaluated in a
      multiplex PCR, determining the sensitivity and the specificity of the technique.
      RESULTS: Reproducible results were obtained with 50 nM of each of the three
      primers and annealing temperature of 57 degrees C in the multiplex PCR, obtaining
      a sensitivity of 12.5 fg for H. influenzae and S. pneumoniae and 3.12 fg for N.
      meningitidis. No cross reactions with other microorganisms agents of meningitis
      or related with the genera, appeared. CONCLUSIONS: The results for sensitivity
      and specificity suggest that the evaluated primers can be used for the
      development of a PCR in a multiplex format to the identification of the three
      main pathogens that cause meningitis.

PMID- 18320112
TI  - [Detection of yellow fever virus by reverse transcriptase polymerase chain
      reaction in wild monkeys: a sensitive tool for epidemiologic surveillance].
AB  - INTRODUCTION: Yellow fever is a zoonotic infection maintained in nature by non
      human primates. Appropriate surveillance with sensitive laboratory techniques is
      necessary to evidence viral activity in the tropical forest habitats of these
      primates. OBJECTIVE: Yellow fever virus was detected in hepatic tissue samples
      from non-human primates by reverse transcriptase polymerase chain reaction (RT
      PCR) technique using specific primers for diagnosis. MATERIALS AND METHODS:
      Hepatic tissue samples were processed from five monkeys belonging genus Alouatta
      spp found dead in sylvatic areas of Cesar and Magdalena Provinces, Colombia,
      between December 2003 and June 2004. Samples were treated with lysis buffer prior
      to the isolation of viral RNA, which was then subjected to reverse transcriptase
      polymerase chain reaction (RT-PCR) using yellow fever-specific primers.
      Simultaneously, viral proteins were identified by immunohistochemistry on parafin
      embedded hepatic tissue. RESULTS: The PCR method amplified fragments of the
      expected size (424 bp) in four of the tested samples. In addition, these samples
      showed a positive reaction by immunohistochemistry, supporting the evidence that
      the virus was present. CONCLUSION: The detection of yellow fever virus in wild
      monkeys was clear evidence of enzootic activity in northern Colombia. Increased
      probability of yellow fever transmission among human populations is indicated due
      to urbanization processes as a consequence of forced migration and displacement
      of the human populations. Molecular tests for rapid and specific detection of
      yellow fever in tissue samples of non-human primates is an important tool for
      epidemiologic surveillance. Rapid virus identification will permit the timely
      activation of control systems for prevention of further cases and epidemic
      situations.

PMID- 18320113
TI  - [XDR-TB, extensively drug-resistant tuberculosis].

PMID- 18320114
TI  - [Congenital tuberculosis associated with maternal disseminated miliary
      tuberculosis].
AB  - Untreated tuberculosis during pregnancy presents a serious risk for transmission
      of disease to the newborn and can result in adverse perinatal and obstetrical
      outcomes. Tuberculosis during pregnancy and congenital tuberculosis are
      infrequent conditions and are difficult to diagnose due the non-specificity of
      the symptoms. A case report is presented of a woman who had no children
      previously with disseminated miliary tuberculosis. Tuberculosis symptoms appeared
      immediately after birth of the first child, with a clinical diagnosis on the
      second month after childbirth, whereupon the patient died. The son, a premature
      infant, showed disease symptoms from the first day, with primary pulmonary
      complex and persistent atelectasis due to bronchial obstruction. The obstruction
      was due to thoracic lymphadenitis and coinfection with cytomegalovirus. The
      infant received standard treatment and his condition improved.

PMID- 18320115
TI  - [Frequency of Trypanosoma cruzi infection in patients with implanted pacemaker].
AB  - INTRODUCTION: In Colombia the impact of infections of Trypanosoma cruzi are known
      to produce chronic cardiopathy and expressed by bradycardia. In Colombia the
      extent and impact of these infections has not been examined. OBJECTIVE: The
      current study aimed to determine the prevalence of T. cruzi infection as measured
      by serology, in a population of patients with cardiopathy that required a
      permanent pacemaker as treatment for cardiac rhythm abnormalities and conduction
      blocking. MATERIALS AND METHODS: A cross sectional study sampled 332 patients
      from the pacemaker clinic at the San Pedro Claver Hospital in Bogota, Colombia,
      for one year (2004-2005). Epidemiological and clinical data were obtained through
      interviews and physical examination. Serological tests consisted of indirect
      inmunofluorescence assay and ELISA. Statistical analyses were accomplished with
      chi-square and Students t tests. RESULTS: Of patients with pacemakers, 17.1% had
      anti-T. cruzi antibodies (seropositive). At the time when the pacemaker was
      implanted, chronic Chagas disease patients were younger (55+/-13 years) than
      those patients with cardiopathy (60+/-17 years) with no anti-T. cruzi antibodies
      (p<0.01). The seropositive group was aware of the Chagas disease vector (83.6%)
      in contrast to the seronegative group (39.6%, p<0.001). In 60% of the patients of
      the seropositive group, no clinical signs of the disease were apparent. The
      geographical origin of the seropositive group were traced to regions in Colombia
      known to be endemic for Chagas disease transmission. CONCLUSION: Chagas disease
      prevalence is high in Colombian patients who required a permanent cardiac
      pacemaker. Chronic Chagas disease patients required pacemaker implant at a
      younger age in contrast with patients with other cardiac pathologies. The
      clinical recognition of Chagas disease associated with cardiopathy is low despite
      the epidemiological data.

PMID- 18320116
TI  - [Adverse reproductive outcomes among women working in Colombian floriculture: a
      summary of the evidence through metaanalysis].
AB  - INTRODUCTION: Workers in floriculture are exposed to pesticides and other risk
      factors. Work in these occupational environments is suspected to be associated
      with adverse reproductive outcomes. However, epidemiological studies in Colombia,
      a country that has a long tradition with this occupation, have not been
      consistent or conclusive. OBJECTIVE: To quantify the effect of womens work in
      Colombian floriculture in the occurrence of spontaneous abortion, prematurity,
      and birth defects, using the results of two previous studies. MATERIAL AND
      METHODS: The results of two previous studies among Colombian floriculture worker
      populations were summarized with metaanalysis techniques. A critical evaluation
      of each of the studies identified potential biases and methodological
      limitations. RESULTS: The pooled estimator of spontaneous abortion was 2.24
      (95CI: 1.87-2.68); that of premature infant birth was 1.49 (95%CI: 0.91-2.43),
      and of birth defects 1.31 (95%CI: 1.95-1.64). CONCLUSIONS: The analyses suggested
      that work in floriculture is associated with a higher occurrence of spontaneous
      abortion and birth defects. However, these effects are not necessarily associated
      with pesticide exposure. Other risk factors requiring further study are levels of
      physical activity and high temperature in greenhouses. Data from countries which
      have initiated occupations in floriculture more recently will add valuable
      evidence for this controversial association.

PMID- 18320117
TI  - [Incidence of and factors for non-compliance to antituberculous treatment].
AB  - INTRODUCTION: Tuberculosis is a public health problem. Non-compliance with
      treatment regimes increases morbidity-mortality, perpetuates transmission and
      generates bacterial resistance. It is necessary to know incidence and associated
      factors to non-compliance for performance interventions. OBJECTIVE: The incidence
      of and associated factors associated with non-compliance to antituberculous
      treatment were investigated. MATERIALS AND METHODS: A follow-up study was
      conducted in an adult cohort with tuberculosis, living in an urban area. Non
      compliance was defined as treatment default of 30 days or more. Patients were
      interviewed at the initiation of treatment and and re-interviewed in subsequent
      intervals. Outcome was defined as the period of time until treatment abandonment.
      Non-compliance rates were calculated, as well as survival curves; the Cox
      regression model was used to adjust for associated variables. RESULTS: Of the 261
      patients who were interviewed, 39 (14.9%) had abandoned treatment (rate 0.4
      episodes/1,000 days-person, 95%CI 0.2-0.8). Factors associated with compliance
      were family support (HR=0.4, 95%CI 0.2-0.9), secondary drug effects (HR=0.2,
      95%CI 0.1-0.6) and opportunity to receive treatment at the clinic where
      tuberculosis was diagnosed (HR=0.3, 95%CI 0.1-0.6). Risk factors for non
      compliance were as follows: treatment requiring >2 months (HR=14.3, 95%CI 1.8
      112.7), low socioeconomic status (HR=3.90, 95%CI 2.1-9.3), age between 21-30
      years (HR=20.6, 95%CI 2.4-175.4), history of incarceration (HR=2.2, 95%CI 1.0
      5.4), skipping treatments more that twice (HR=6.6, 95%CI 2.8-15.6) and co
      infection with HIV/AIDS (HR=2.9, 95%CI 1.6-5.4). CONCLUSION: Non-compliance rate
      is higher than previously reported. The data recommend the following strategies
      for improving compliance with antituberculosis treatment: (1) early diagnosis,
      (2) opportune treatment, (3) improved family support and (4) immediate
      intervention if a treatment is missed -especially in patients with HIV/AIDS, from
      low socioeconomic strata, or with record of incarceration.

PMID- 18320118
TI  - [Leptin levels in school age children associated with anthropometric measurements
      and lipid profiles].
AB  - INTRODUCTION: Leptins are proteins that regulate body weight. Their
      concentrations are modified depending on several factors including metabolic
      status, diabetes mellitus type 2 and cardiovascular diseases. OBJECTIVE: The
      leptin concentrations were measured in Colombian children and related to age,
      sex, body mass index, triceps skinfold and lipid profile. MATERIALS AND METHODS:
      School age children from 5 provinces of central-eastern Colombia were examined.
      Measurements included body mass index, body fat reserves, leptin concentrations
      and lipid profile. RESULTS: The overall leptin concentrations were 8.3+/-8.9
      ng/ml. The concentrations varied by differences in the age and sex, but were
      equal in children with higher body weight and greater fat deposition. A positive
      relationship was observed between high leptin levels and high total cholesterol
      in males, and in females, an association of high leptin levels with high levels
      of triglycerides. CONCLUSION: The leptin concentrations followed a trend similar
      to those of other population groups with differences according to the age, sex
      and deposits of fat mass. However, the values seem to be influenced by hormonal
      differences and food habits. In addition, overweight or obese school children
      probably have hyperleptinemia, correlated to metabolic syndrome, diabetes
      mellitus type 2 and cardiovascular diseases. The sex specific association between
      total cholesterol, triglycerides and leptin suggests a complex relationship that
      depends on biological and hormonal differences, as well as environmental and life
      style differences. Each of these associations requires additional focused study
      for verification.

PMID- 18320119
TI  - [Effectiveness of prophylaxis against tuberculosis in patients infected with
      HIV].
AB  - INTRODUCTION: Prophylaxis against tuberculosis has been recognized as important
      for preventing clinical forms of tuberculosis, mainly in HIV positive patients.
      However, in countries with high tuberculosis prevalence, prophylaxis application
      and effectiveness remains controversial. OBJECTIVE: Effectiveness was established
      for two prophylaxis regimens -isoniazid treatment for nine months and
      pirazinamid/rifampin for 60 days. MATERIALS AND METHODS: Two cohort groups of
      patients diagnosed with HIV/AIDS were compared. One consisted of 131 volunteer
      patients, who received one of the two prophylactic regimens -pirazinamid/rifampin
      or isoniazid. The tuberculosis treatment drugs were self-administered and
      independent of tuberculin response tests. The second group consisted of 200
      patients selected from the records of a HIV/AIDS control program. Follow up for
      both groups was conducted over a two-year period through clinical records.
      RESULTS: The 2 groups were similar with respect to clinical and demographic
      variables. A higher proportion of patients in the control group had CD4 counts
      <200/ml and viral load >100,000 copies. In the prophylactic group, 8% of patients
      reported adverse effects due to the drug, and one person had tuberculosis in that
      group (0.8%). Ten persons in the control group contracted tuberculosis (5%)
      RR=0.15, 95%CI 0.02-1.18, p=0.07. The prophylaxis protective level was calculated
      to be 80%, after taking into account CD4, viral load, and effective
      antiretroviral therapy. CONCLUSION: The prophylaxis against tuberculosis was
      effective in HIV positive patients, independently of the immune status, viral
      load, and highly effective antiretroviral therapy.

PMID- 18320120
TI  - [Genetic polymorphism of the E apolipoprotein in school age children: comparison
      with levels of plasma lipids and apolipoproteins].
AB  - INTRODUCTION: Research in laboratories around the world has documented the
      contribution of the E apolipoprotein alleles to structural variations of lipids
      and apolipoproteins. OBJECTIVE: The gene frequencies of the E apolipoprotein
      alleles were compared with the lipid and apolipoprotein levels in school age
      children. MATERIALS AND METHODS: Six hundred and ninety one 5 to 15 years old
      school age children from the Colombian departments of Cundinamarca, Boyaca, Meta,
      Santander and Norte de Santander, were evaluated. The genotypes of the E
      apolipoprotein were identified by polymerase chain reaction-restriction fragment
      length polymorphism. Plasma levels for the following 5 lipids and lipoproteins
      were assayed: total cholesterol, HDL (high density lipoprotein) cholesterol, LDL
      (low density lipoprotein) cholesterol, triglycerides, VLDL (very low density
      lipoprotein) cholesterol, A-I apolipoprotein and B-100 apolipoprotein. RESULTS:
      Alleles e2, e3 and e4 were found in frequencies of 0.04, 0.86 and 0.08,
      respectively. The E4 group (E4/3-E4/4), in contrast with the E2 group (E3/2
      E2/2), presented highest plasma concentrations of total cholesterol, LDL
      cholesterol and B-100 apolipoprotein (p=0.014, 0.001 and 0.000, respectively).
      When the E3/3 group was compared with E2, the same result was obtained (p=0.015,
      0.002 and 0.002, respectively). The influence of the E apolipoprotein
      polymorphism appeared greater in female children than male. CONCLUSIONS: The e4
      allele was associated with higher levels of total cholesterol, LDL cholesterol
      and B-100 apolipoprotein and indicates the necessity of additional research into
      the interactions between polymorphism E apolipoprotein and other genes, life
      styles, risk factors and potential contribution to cardiovascular diseases.

PMID- 18320121
TI  - [Human leucocyte antigen gene (HLA-A, HLA-B, HLA-DRB1) frequencies in deceased
      organ donors].
AB  - INTRODUCTION: Genetic characterization of the human leucocyte antigen (HLA)
      system has provided insights into mechanisms of susceptibility to diverse
      diseases and immunological phenomena during pregnancy, as well as providing
      evidence for compatibility in the selection of organ transplant donors and
      recipients. OBJECTIVE: The HLA-A,-B,-DRB1 allele, genotype and haplotype
      frequencies were determined in deceased organ donors in Medellin, Colombia.
      MATERIALS AND METHODS: The genotypes of 926 deceased donors were evaluated over a
      17-year period (1989- 2006). HLA-A, HLA-B and HLA-DRB1 typing was performed by
      sequence specific primer-polymerase chain reaction (SSP-PCR). Maximum likelihood
      frequencies were estimated by the zipper version of expectation maximation
      algorithm. Hardy-Weinberg equilibrium were determined by an exact test analogous
      to Fishers test by using Markovs chain, and linkage disequilibrium between pairs
      of loci. RESULTS: Twenty-two, 43 and 14 alleles were identified for HLA-A, -B and
      -DRB loci, respectively. The most frequent were A*02, A*24, B*35, and DRB1*04. A
      deficiency in the proportion of heterozygotes in HLA-A and B loci (p<0.01 and
      p<0.00001, respectively). The most frequent haplotypes were as follows: HLA-A*24,
      B*35 (7.7%) for HLA-A,-B; HLA-B*35, DRB1*04 (6.4%) for HLA-B,-DRB1 and HLA-A*24,
      DRB1*04 (8.9%) for HLA-A,-DRB1. For the 3 loci HLA-A,-B,-DRB1, the most frequent
      haplotypes were A*24, B*35, DRB1*04 (4.6%) and A*24, B*61, DRB1*04 (2.0%).
      CONCLUSIONS: These results confirm the three-ethnic ancestry of the Medellin
      population. The predominance of Caucasian admixture differs from many other Latin
      American populations and can serve as a reference for comparative studies of
      these populations as well as applications within the Medellin population.

PMID- 18320122
TI  - [Decreased number neurons expressing GABA in the cerebral cortex of rabies
      infected mice].
AB  - INTRODUCTION: GABAergic neurons synthesize and release gamma-aminobutyric acid,
      the predominant inhibitory neurotransmitter in the brain. Certain clinical signs
      of rabies and previous experimental studies have suggested that rabies viral
      infections affect the host GABAergic system. OBJECTIVE: The effect of rabies
      virus infection on the expression of GABA was evaluated in neurons of the mouse
      cerebral cortex. MATERIALS AND METHODS: Adult mice were inoculated by
      intramuscular injection with the standard strain of rabies (CVS virus). The
      animals were sacrificed in the terminal stage of the illness and perfused with 4%
      paraformaldehyde and 1% glutaraldehyde. Frontal sections were obtained in a
      Vibratome(R) and treated with appropriate immunohistochemical reactions for
      identifying the GABAergic neurons in the cerebral cortex. Counts and comparative
      quantitative analysis of the GABA+ neurons were compared in samples of infected
      and normal mice. RESULTS: In the animals infected with rabies virus, the
      distribution pattern of cortical GABAergic neurons was not changed, but their
      number diminished significantly. The mean value of GABA+ cells number in 1
      microm2 of cerebral cortex was 293+/-32 in normal samples and 209+/-13 in
      infected samples. Despite the loss in GABA+ cell number, the average size of
      GABA+ cells per unit increased from 104+/-8 microm2 in normal mice to 122+/-10
      microm2 in infected mice because the cell loss consisted more frequently of
      smaller neurons. Nevertheless, the rank of GABA+ cell sizes in infected samples
      was similar to normal samples. CONCLUSION: This evidence supported the hypothesis
      that GABA is involved in rabies pathology.

PMID- 18320123
TI  - [Nutritional status of children with malaria in northwest Colombia].
AB  - INTRODUCTION: Malaria and malnutrition coexist within the poorest regions of the
      world. In the regions of Colombia where malaria is endemic, malnutrition is also
      a public health problem. OBJECTIVE: The prevalence of malnutrition in children
      with malaria was determined and several factors associated with malnutrition were
      identified. MATERIALS AND METHODS: A total of 93 children with malaria were
      included. They resided in the municipalities of Turbo and El Bagre (Antioquia,
      Colombia) and volunteered for an experimental, study to evaluate the outcome of
      an antimalarial treatment with a vitamin A supplement and an anti-intestinal
      parasite treatment administered as a single dose. At enrollment, the nutritional
      status was evaluated by anthropometry, and a survey questionnaire was
      administered about economic and social conditions of the family. RESULTS:
      Prevalence of moderate or severe chronic malnutrition was 22.6%-10.8% of children
      had moderate or severe global malnutrition and 2.3% had acute malnutrition. The
      prevalence of malnutrition was higher in males and in children from Turbo.
      CONCLUSIONS: Prevalence of malnutrition was higher than previously reported by
      the National Health and Demography Survey (2005) and, in Turbo, the prevalence
      was higher than that reported for the rest of the Uraba region of Antioquia.

PMID- 18320124
TI  - [Evaluation of two rapid diagnostic tests, NOW ICT Malaria Pf/Pv and OptiMAL, for
      diagnosis of malaria].
AB  - INTRODUCTION: To increase the accessibility of malaria diagnosis, the Instituto
      Nacional de Salud de Colombia undertook a field trial to evaluate the sensitivity
      and specificity of two rapid diagnostic tests. OBJECTIVE: The sensitivity,
      specificity and concordance was compared for two rapid diagnostic tests for
      malaria, NOW ICT Malaria Pf/Pv and OptiMAL. MATERIALS AND METHODS: A descriptive
      and concordance study was performed with 214 patients in the southwestern coastal
      city of Tumaco, Colombia, each of whom presented at least one of the symptoms of
      the classical malaria triad. Two strategies were applied for patient recruitment
      one by passive search and a second through local health brigades. RESULTS: NOW
      ICT showed a general sensitivity of 98.4% (95%CI: 90.3-99.9), and a general
      specificity of 98.0% (95%CI: 93.9-99.5). For Plasmodium falciparum, the
      sensitivity was 98.2% (95%CI: 89.4-99.9) and the specificity 98.1% (95%CI: 94.1
      99.5). The sensitivity was lower (80.0%) when parasitemia ranged from 200 to
      4,000 parasites/microl. The sensitivity and specificity of the NOW ICT for P.
      vivax malaria were 100%. The sensitivity for this test was not affected for the
      established ranges of parasitemia for P. vivax. The overall figures for OptiMAL
      were 95.2% (95%CI: 85.8-98.8) sensitivity and 99.3% (95%CI: 95.8-100.0)
      specificity. For P. falciparum malaria OptiMAL showed 94.7% (95%CI: 84.5-98.6)
      sensitivity and 99.4% (95%CI: 96.0-100.0) specificity. The sensitivity was lower
      (60.0%) when samples with 200-4,000 parasites/microl were tested. For P. vivax,
      OptiMAL presented a 66.7% (95%CI: 24.1-94.0) sensitivity, which diminished to 50%
      with a parasitemia between 300-2.500 parasites/microL. CONCLUSIONS: Good results
      for sensitivity and specificity were obtained for malaria diagnosis using NOW ICT
      and OptiMAL, with NOW ICT showing higher sensitivity and specificity values than
      OptiMAL.

PMID- 18320125
TI  - [Clinical profiles of patients with uncomplicated Plasmodum falciparum malaria in
      northwestern Colombia].
AB  - INTRODUCTION: Few studies describe the clinical presentations of uncomplicated
      Plasmodium falciparum malaria in the province of Cordoba in an endemic area of
      northwestern Colombia. OBJECTIVE: Profiles of patients with uncomplicated
      Plasmodium falciparum malaria were described from two twons of Cordoba, Tierrata
      and Puerto Libertador, based on clinical, epidemiological and laboratory
      variables. MATERIALS AND METHODS: Patients were examined according to standard
      WHO/PAHO protocols for assessment of antimalarial drug efficacy. Clinical data
      and parasitological information was collected as well. A multiple correspondence
      multivariate analysis was used to compare the profiles of 127 patients with
      uncomplicated Plasmodium falciparum malaria. RESULTS: Of the 127 patients,105
      completed the 14-day follow-up and 7 had adequate clinical response. Between 80%
      and 98% of patients exhibited at least one of the most frequent symptoms of
      uncomplicated malaria, and 80.3% had asthenia as the most frequent symptom. The
      multivariate analysis grouped the variables into five distinguishable clusters of
      clinical profiles. These groups showed similarities with the classical clinical
      descriptions of uncomplicated malaria encountered in the literature. The low
      frequency of patients with adequate clinical response hampered the association
      analysis. CONCLUSIONS: In Cordoba, therapeutic failure to chloroquine treatment
      is high in treating uncomplicated Plasmodium falciparum malaria. Multivariate
      analysis summarized variables related to epidemiological and clinical aspects and
      permitted a more objective approach to the interpretation of the findings.

PMID- 18320126
TI  - [Cytotoxicity of the herbicide glyphosate in human peripheral blood mononuclear
      cells].
AB  - INTRODUCTION: Glyphosate is a broad-spectrum, non-selective herbicide and
      commonly used to eliminate weeds in agricultural and forest settings. Studies
      evaluating glyphosate toxicity in animals and environment show that commercial
      formulations of glyphosate are more toxic than the active component itself.
      OBJECTIVES: Technical grade glyphosate was compared with the commercial
      formulation Roundup in their respective toxicities on human peripheral blood
      mononuclear cells. MATERIALS AND METHODS: Human peripheral blood mononuclear
      cells were exposed to different concentrations of glyphosate, either technical
      grade or in the form of Roundup for 24 h, 48 h, 72 h, and 96 h. Cytotoxicity was
      assayed by trypan blue dye exclusion method and reduction of (2,3-bis[2-methoxy-4
      nitro-5-sulfophenyl]-2Htetrazolium-5-carboxyanilide inner salt)XTT reagent.
      RESULTS: Both technical grade glyphosate and Roundup formulation were toxic to
      human peripheral blood mononuclear cells. Cytotoxicity of Roundup was higher than
      cytotoxicity of glyphosate, since the LC50 (50% lethal concentration) determined
      by the trypan blue exclusion method at 24 h was the equivalent of 56.4 microg/ml
      of glyphosate in the form of Roundup and 1,640 microg/ml (1.64 mg/ml) for
      technical grade glyphosate. CONCLUSIONS: This in vitro study confirmed the toxic
      effects on human cells by glyphosate and its commercial preparations. Commercial
      formulations were more cytotoxic than the active component alone, supporting the
      concept that additives in commercial formulations play a role in the toxicity
      attributed to glyphosate-based herbicides.

PMID- 18320127
TI  - [Neuronal dentritic morphology alterations in the cerebral cortex of rabies
      infected mice: a Golgi study].
AB  - INTRODUCTION: The neurological signs of rabies are very dramatic. Nevertheless,
      the infected brain manifests only very subtle histological changes. OBJECTIVE:
      The neuronal morphology in the cerebral cortex of rabies-infected mice was
      examined by means the Golgi technique for detection of neuropathy. MATERIALS AND
      METHODS: Two groups of mice were inoculated with rabies-one with street virus
      isolated from an infected dog and the second with fixed CVS (challenge virus
      standard) virus. At the terminal phase of illness, the animals were sacrificed
      and fixed for histological staining by perfusion with paraformaldehyde. Next, the
      brains were treated by the Golgi technique and coronal sections were obtained.
      Neurons enclosed within 1 mm2 frames of the frontal cortex sections were counted
      and the sizes of the cellular bodies were measured. Photographs of several depth
      levels from the sections were obtained. RESULTS: Cortical pyramidal neurons
      showed distinctive morphological alterations in the soma and dendrites (including
      loss of dendritic spines) in 12.9% of cells from intracerebral infected-mice with
      street virus; in 8.2% of neurons from intramuscular infected-mice with street
      virus, and in 31.8% of neurons from mice injected intramusculary with fixed
      virus. In addition, the number of neurons impregnated by the Golgi technique in
      infected brains was considerably lower than in the non-infected samples.
      CONCLUSIONS: Rabies virus can induce structural neuron damage. The infection also
      appears to induce tissue changes that interfere with the chemical mechanisms of
      the Golgi silver impregnation method.

PMID- 18320128
TI  - Younger onset of depression is associated with greater suicidal intent.
AB  - BACKGROUND: Age of onset of major depression seems to be dropping in Western
      nations. Early onset usually predicts a more serious illness with a relatively
      poor prognosis. Since depression is associated with suicide, this begs the
      question of whether early onset of depression is associated with the degree of
      intent of suicidal behaviour, and whether this relationship differs according to
      gender. METHODS: Relevant responses from 9,282 residents of the United States
      were drawn from a nationally representative community survey conducted in 2001
      through 2003 using the W.H.O. version of the Composite International Diagnostic
      Interview. The primary outcome measure was the retrospectively determined age of
      first major depressive episode. RESULTS: Younger age of onset for depression was
      associated with higher levels of suicidal intent, irrespective of age at the time
      of interview. A significant interaction between level of intent and age at
      interview appeared to be accounted for by the later onset among those in the
      eldest cohort who reported an absence of suicidal behaviour. The influence of
      suicidal intent on onset of depression was greater for women than for men.
      CONCLUSIONS: The earlier the age of first symptoms of major depressive episode,
      the higher the degree of suicidal intent, irrespective of age at interview and
      gender, although the more pronounced trend for women suggests a greater
      sensitivity to underlying factors that may involve depression and lead to suicide
      risk.

PMID- 18320129
TI  - Ambulatory care provision versus first admission to psychiatric hospital: 5 years
      follow up.
AB  - OBJECTIVE: Ambulatory care for subjects with severe mental problems has been
      clearly shown to be a valid alternative to hospitalisation. However, very few
      studies have considered the fate of patients over several years. Ambulatory care
      services are often experimental set-ups, for small groups, and their impact on
      subsequent treatment has only been assessed over the first few months of
      treatment. The value of developing this practice therefore remains unclear. We
      investigated the possible consequences of generalising ambulatory care services
      by a mobile crisis intervention team (ERIC) to all requests for the first
      hospitalisation in a psychiatric department. The principal aim was to determine
      whether systemic intervention by the crisis intervention team could provide a
      true alternative to hospitalisation. We also investigated whether problem
      resolving approaches and ambulatory care led, in the long term, to fewer
      prolonged or repeated periods of hospitalisation than practices in which
      hospitalisation was considered as an ordinary solution. METHODS: We carried out a
      prospective, comparative, cohort study over a 5-year period beginning with the
      creation of ERIC by one of the hospital departments. All patients arriving at
      this department for the first time were offered immediate ambulatory care by this
      team for 1 month. Their hospitalisation record (duration of hospital stay, number
      of days in hospital) was compared with that of subjects hospitalised in the same
      conditions but in other departments of the hospital. RESULTS: This study included
      most of the subjects referred for the first time to the psychiatric hospital, in
      our department. Regardless of their diagnosis, intensive follow-up at home, based
      on systemic crisis intervention work, was found to be an effective and well
      accepted alternative to hospitalisation. Indeed, a highly significant immediate
      decrease in both the number of admissions and the duration of hospital stay was
      observed for the experimental group, with no subsequent increase in the number of
      days of hospitalisation. From the second year onwards, the use of hospitalisation
      did not seem to be influenced by the type of care initially given to the patient.
      Rehospitalisation was rare in both groups. One third of the patients in the
      experimental group benefited from another intervention of the ambulatory
      emergency team from the second year onwards, highlighting the value placed on
      this type of care by the patients and their families. CONCLUSION: Our results
      support the development of ambulatory crisis intervention services, including
      those from psychiatric hospitals. Clinical studies following the treatment paths
      of patients in a more exhaustive manner would almost certainly distinguish more
      precisely between the "natural" course of the disease and the impact of the care
      provided. In any case, the prevention of hospitalisation must be based as much on
      a possible alternative at the time of the crisis as on subsequent access to
      ambulatory care.

PMID- 18320130
TI  - Occurrence of glyphosate in surface waters of Southern Ontario.
AB  - Glyphosate in surface waters of southern Ontario (Canada) was studied over a 2
      year period. A small percentage of samples exhibited glyphosate concentrations
      greater than the analytical limit of quantitation (17 microg a.e./L), and the
      maximum concentration of glyphosate measured was 40.8 microg/L. No samples of
      roughly 500 analyzed exceeded the Canadian Water Quality Guideline of 65 microg
      a.e./L considered protective of aquatic life. Typical concentrations of
      glyphosate in amphibian habitats were well below a range of toxicity thresholds
      for aquatic organisms, and were thus judged to be unlikely to pose a substantial
      risk to either sensitive amphibian larvae or other aquatic biota.

PMID- 18320131
TI  - Water quality and trace metal distribution in a pristine Lake in the Lake basin
      in Kenya.
AB  - Water and surface sediment samples taken from various locations within Lake
      Kanyaboli in the Lake Victoria basin were analysed to determine the concentration
      and distribution of heavy metals. There were wide ranges in concentrations of the
      metals among the sampling points analysed. Sediment concentrations (microg/g dry
      weight) ranged from n.d.-2.54 (Ag), 0.25-1.08 (Cd), 0.89-1.64 (Co), 3.7-7.73
      (Cr), 1.80-30.27 (Cu), 1073-2627 (Mn), 22.61-55.60 (Ni), 11.42-153.9 (Pb), 40.46
      154.7 (Sn) and 65.0-146.5 (Zn). Dissolved metal concentrations (microg/L) ranged
      from n.d.-9.22 (Ag), n.d.-5.54 (Cd), n.d.-8.30 (Co), 5.26-60.82 (Cr), 10.96-43.11
      (Cu), 184.7-375.9 (Mn), 1.84-38.3 (Ni), 5.98-47.77 (Pb), n.d.-540.6 (Sn) and 14.5
      55.9 (Zn). Compared with WHO standards and other freshwaters worldwide, this lake
      was found to be unpolluted, with all metals, except Mn, being detected at
      concentrations lower than the highest desirable levels and maximum permissible
      levels. Some of the toxic metals, Cu, Zn, Pb and Cd (in sediment) and Ag, Co and
      Pb (in water) were detected at lower concentrations than those found in the
      polluted Kisumu Pier in Winam Gulf in the Lake basin, which confirms the
      anthropogenic influence on the latter.

PMID- 18320132
TI  - Polybrominated diphenyl ethers in human serum and sperm quality.
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants;
      currently, they are identified as ubiquitous environmental contaminants. Several
      studies indicate that PBDEs might affect male fertility. We present the results
      of a pilot study on the relationship between human serum PBDEs and sperm quality.
      The PBDE levels in Japan are comparable to those found in European countries.
      Strong inverse correlations were observed between the serum concentration of
      2,2',4,4',5,5'-hexabromodiphenyl ether and sperm concentration (r = -0.841, p =
      0.002) and testis size (r = -0.764, p = 0.01). Extensive studies on the
      relationship between PBDEs and sperm quality are required.

PMID- 18320133
TI  - Influence of factors regulating bone formation and remodeling on bone quality in
      osteonecrosis of the femoral head.
AB  - Osteonecrosis of the femoral head (ONFH) usually affects young individuals and
      has a major impact on lifestyle. Notably, the pathogenetic mechanisms of
      osteonecrosis are unresolved and no effective treatment exists. The objective of
      this study was to assess the gene expression levels of factors regulating bone
      formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2,
      osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to
      those of patients with primary osteoarthritis (OA). The cellular and
      macromolecular composition of the bone matrix was assessed by osteocalcin
      immunohistochemistry, and the three-dimensional organization of trabecular bone
      was characterized by micro-computed tomographic analysis. Our results demonstrate
      that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with
      ONFH. We observed increased extracellular osteocalcin deposition, presumably
      caused by a higher number of osteoblasts in concordance with increased activity
      of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast
      differentiation rate in ONFH bone. We found no significant change in bone volume,
      connectivity, and structural model index; further, no significant differences
      were detected for trabecular properties in ONFH bone. In conclusion, we have
      shown increased gene expression of factors regulating bone formation and
      remodeling in the femoral head and/or neck of patients with ONFH. Further, we
      observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte
      cell number, while no significant changes in trabecular microarchitecture were
      detected. This study increases our understanding of the pathophysiology and
      repair process following ONFH and might help in the development of new treatment
      strategies in the future.

PMID- 18320134
TI  - Comparative study of the anatomy, CT and MR images of the lateral collateral
      ligaments of the ankle joint.
AB  - Clinical diagnosis of lateral collateral ligamentous injury caused by ankle
      sprains depends primarily on clinical signs, and X-ray and CT images. None of
      these, however, provide direct or accurate information about ligamentous injury.
      MRI has long been testified as a useful tool in the demonstration of ligaments
      due to its good resolution of soft tissues. We confirmed the appearance of the
      lateral collateral ligaments of the ankle joints on MR images by comparing MR
      images with CT images of the ligaments enhanced by coating with contrast medium
      after dissection of six cadaver feet. Compare study of MR images reveals no
      difference in the natural position and the dorsal position (P > 0.05), whereas,
      taken into the consideration the long hour of MRI examination, the natural
      position is regarded as the optimal position for MRI performance. Measured on
      transverse MR images, lateral ligaments of acutely injured ankles were
      significantly thicker than those of normal ankles (P < 0.01). According to the MR
      images of normal and injured ankles, the lateral collateral ligaments injuries
      were classified as type I and type II. Osteal contusion, cartilaginous injury,
      musculotendinous injury, tenosynovitis, and peritenosynovitis were also observed
      by MRI in type I and type II acute lateral collateral ligament injury. All these
      complications have higher incidence in type II than in type I injury (P < 0.05).
      Thus, by comparing with the CT images and the anatomy we confirmed the normal
      appearance of the lateral collateral ligaments on MR images and figured out that
      the natural position is the optimal position for MRI performance. The thickness
      of the ligaments and incidence of the complications could be regarded as useful
      cue for the assistant in clinical diagnosis of the lateral collateral ligament
      injury.

PMID- 18320135
TI  - Pregnant woman and road safety: experimental crash test with post mortem human
      subject.
AB  - BACKGROUND: Trauma affect between 3 and 7% of all pregnancies in industrialized
      countries, and the leading cause of these traumas is car crashes. The difficulty
      to appreciate physiologic and anatomic changes occurring during pregnancy explain
      that majority of studies were not based on anatomical data. We present a protocol
      to create a realistic anatomical model of pregnant woman using a post mortem
      human subject (PMHS). METHODS: We inserted a physical model of the gravid uterus
      into the pelvis of a PMHS. 3D acceleration sensors were placed on the subject to
      measure the acceleration on different body segments. We simulated three frontal
      impact situations at 20 km/h between two average European cars. RESULTS: Two main
      kinematics events were identified as possible causes of injuries: lap belt
      loading and backrest impact. CONCLUSIONS: Cadaver experiments provide one
      interesting complementary approach to study injury mechanisms related to road
      accidents involving pregnant women. This anatomical accuracy makes it possible to
      progress in the field of safety devices.

PMID- 18320136
TI  - Characterization of tomato zonate spot virus, a new tospovirus in China.
AB  - An isolate of a new tospovirus species, causing concentric zoned ringspots on
      fruits and necrotic lesions on leaves of infected plants, was characterised based
      on particle morphology, host range and serological properties. The complete
      nucleotide sequences of large (L), medium (M), and small (S) RNAs of this virus
      were found to contain 8919, 4945, and 3279 nts respectively. The L RNA encoded
      the RNA-dependent RNA polymerase (RdRp) (2885 aa, 332.7 kDa). The M RNA encoded a
      non-structural (NSm) protein (309 aa, 34.4 kDa) and a viral glycoprotein
      precursor (Gn/Gc) (1122 aa, 127.4 kDa). The S RNA encoded a non-structural
      protein (NSs) (459 aa, 51.9 kDa) and the nucleocapsid (N) protein (278 aa, 30.6
      kDa). This N protein shared amino acid identities of 80.9% with those of calla
      lily chlorotic spot virus. Our results suggest that the virus studied here
      belongs to a new tospovirus species, for which the name tomato zonate spot virus
      is proposed.

PMID- 18320137
TI  - The evaluation of latent tuberculosis in rheumatologic diseases for anti-TNF
      therapy: experience with 192 patients.
AB  - It is recommended to evaluate the presence of latent tuberculosis infection
      (LTBI) before initiating antitumor necrosis factor alpha (anti-TNF) therapy for
      rheumatologic diseases. We aimed to present the follow-up results of 192 patients
      with rheumatologic diseases before anti-TNF therapy for LTBI. We enrolled 192
      patients who were given anti-TNF therapy for their rheumatologic diseases between
      April 2005 and January 2008. The demographic characteristics of the patients were
      recorded. Chest X-ray was obtained and tuberculin skin test (TST) was performed
      in all patients before anti-TNF therapy. LTBI was assessed by detailed history of
      close contact with infectious cases within the last year, abnormal chest
      radiography, and positive TST (> or =5 mm) before initiating anti-TNF therapy.
      Patients with anti-TNF therapy were followed with 2-month intervals for active
      tuberculosis by pulmonary and extrapulmonary symptoms, physical examination, and
      chest X-ray. Of 192 patients, 104 (54.2%) patients were women, age (mean +/- SD)
      43.1 +/- 12.7 years and 88 (45.8%) patients were men, age (mean +/- SD) 39.3 +/-
      11.2 years. Ninety-one (47.4%) of them had rheumatoid arthritis (RA); 92 (47.9%)
      had ankylosing spondylitis (AS), and nine (4.7%) had psoriatic arthritis.
      Isoniazid treatment was started in 129 (67.2%) patients in whom LTBI was
      detected. No significant difference was observed for TST positivity (TST > or = 5
      mm) between the patients with RA and AS (p = 0.101). Similarly, no significant
      difference was also observed for TST positivity between the patients who received
      immunosuppressive therapy and those who did not (p = 0.154). Only three (1.6%)
      patients developed active tuberculosis at the study period. We suggested that in
      despite of the presence of rheumatologic disease and/or immunosuppressive
      therapy, TST is an acceptable and available diagnostic test for detecting LTBI
      before anti-TNF therapy.

PMID- 18320138
TI  - Clinical features of late cytomegalovirus infection after hematopoietic stem cell
      transplantation.
AB  - Late cytomegalovirus (CMV) disease beyond day 100 after hematopoietic stem cell
      transplantation (HSCT) has become an increasing problem after the introduction of
      preemptive ganciclovir (GCV) administration. To clarify the risk factors and
      outcome for late CMV reactivation and disease, we retrospectively analyzed the
      records of 101 Japanese adult patients who underwent allogeneic HSCT between 1998
      and 2005 at our hospital. Fifty-one developed late positive CMV antigenemia, with
      a cumulative incidence of 53%. Recipient CMV seropositivity, the use of
      alemtuzumab, chronic GVHD, and high-dose steroids were significantly associated
      with late positive antigenemia. Eight patients developed late CMV disease, with a
      cumulative incidence of 8%, including retinitis and gastrointestinal disease.
      None progressed to a fatal disease. The use of alemtuzumab was identified as an
      independent significant risk factor for late CMV disease, although it was not
      associated with increased non-relapse mortality. Among the 51 patients with late
      positive antigenemia, 28 had consistently less than three positive cells, 25 of
      whom showed negative conversion without antiviral agents. In conclusion, late CMV
      antigenemia appeared to develop frequently, especially in patients with profound
      immune suppression; however, a fatal outcome could be prevented by optimal
      preemptive therapy. Low-level antigenemia may not require antiviral treatments.

PMID- 18320139
TI  - HCV non-structural protein 3 and HCV RNA genome in non-Hodgkin lymphoma and
      transition of the serum HCV RNA level: a retrospective analysis in one
      institution.
AB  - There have been various reports on the association of hepatitis C virus (HCV)
      infection with B lymphocyte proliferative disorders, such as non-Hodgkin lymphoma
      (NHL). We experienced a case (Case 1) of anti-HCV antibody (HCV-Ab)-positive NHL
      in which HCV nonstructural protein 3 (NS3) expression was observed in lymphoma
      tissue at the time of recurrence and in which the serum HCV RNA level exhibited a
      transient increase prior to recurrence. We investigated the HCV RNA genome in
      lymphoma tissue in Case 1, and it could be detected at recurrence. We also
      investigated HCV NS3 protein expression in lymphoma tissue and changes in serum
      HCV RNA level during the clinical course in four other cases of HCV-Ab-positive
      NHL treated in our hospital. We examined lymphoma tissues for HCV NS3 protein
      expression in four of the five cases, but it was not identified except for in
      Case 1 at recurrence. In three cases with no recurrence, serum HCV RNA levels
      showed a tendency to decrease after completion of chemotherapy and became stable
      thereafter. Further studies are necessary to clarify the association between
      serum HCV RNA and the onset and exacerbation of NHL.

PMID- 18320140
TI  - Primary intracranial myxoma of the parietal region. Illustrated case report.
AB  - An extremely rare case of primary intracranial myxoma mimicking an intraaxial
      parenchymal tumour is reported. A 25 year old male presented with complaints of
      headache and right sided hemiparesis. A gross total resection of the tumour was
      achieved. Histology confirmed that the tumour was a myxoma. Investigations did
      not reveal any underlying cardiac focus. Following surgery, the patient had rapid
      recovery from his symptoms and on a follow up at 3 months was asymptomatic.
      Primary intracranial myxomas are extremely rare and this is the fifth reported
      case in neurosurgical literature and third report of supratentorial myxoma.
      Though metastatic myxomas from atrial myxomas are known to occur primary
      intracranial myxomas are extremely rare. Surgical resection provides an excellent
      prognosis and the surgical aim should be to achieve total resection.

PMID- 18320141
TI  - Occurrence of a germinoma 22 years after resection of a mature cerebral teratoma.
AB  - We present the rare case of a 31-year-old man who developed a germinoma 22 years
      after resection of a mature teratoma of the pineal region. The initial
      stereotactic biopsy showed a granulomatous inflammation, but no malignant cells.
      The correct diagnosis could only be confirmed in a second cerebral biopsy,
      allowing for proper treatment with radiation therapy. The need to consider
      metachronous germinoma in this setting is discussed.

PMID- 18320142
TI  - Chordoid meningioma: presentation of two case reports, review of the literature,
      and plea for data standardisation.
AB  - Chordoid meningioma is a rare variant of meningioma with histological features
      resembling those of chordoma. This tumour should have a greater risk of
      recurrence and aggressive growth (WHO grade II). So far, 92 such tumours have
      been described in the literature. We report two cases of chordoid meningioma
      occurring in adult female patients. In our two patients (aged 28 and 60 years
      with chordoid meningioma of the convexity and left-sided outer sphenoid wing,
      respectively) we centred on some rarely discussed aspects of the tumour. MRI
      scans showed no edema in the vicinity of either of the two meningiomas, whereas
      selective angiography of ACI and ACE revealed a dural type of vascular supply to
      the two neoplasms. In both cases, the tumour was removed by radical surgery
      (Simpson grade I resection) with a normal post-operative course. Both women (one
      2 years post-surgery and one 4 years post-surgery) are now free from any signs of
      relapse on MRI and with normal neurological findings. The vascular endothelial
      growth factor (VEGF) expression was low in either case (5 and 40%, respectively).
      We regard the factors under consideration in our study (i.e. absence of edema,
      dural supply, low VEGF expression and radical Simpson grade I resection) as an
      important contribution to the discussion of the biological behaviour of chordoid
      meningioma.

PMID- 18320143
TI  - Factors affecting xylanase functionality in the degradation of arabinoxylans.
AB  - Endo-beta-1,4-xylanases are key enzymes in the degradation of arabinoxylans, the
      main non-starch polysaccharides from grain cell walls. Due to the heterogeneity
      of arabinoxylans, xylanases with different characteristics are required in
      industrial applications but the choice of the enzyme is still largely empirical.
      Although the classification into glycoside hydrolase families greatly helped to
      derive mechanistic information on the catalytic and substrate specificity of
      xylanases, other factors e.g. their sensitivity to endogenous inhibitors, the
      presence of carbohydrate-binding module(s) and their degree of selectivity
      towards soluble versus insoluble substrate may play a role in determining the
      functionality of these enzymes in the degradation of arabinoxylans.

PMID- 18320144
TI  - Efficacy of silver nanoparticles-impregnated external ventricular drain catheters
      in patients with acute occlusive hydrocephalus.
AB  - INTRODUCTION: Catheter-associated infection of cerebrospinal fluid (CSF) is a
      potentially life-threatening complication of external ventricular drainage (EVD).
      The purpose of this pilot study was to address the efficacy of silver-impregnated
      EVD catheters in neurological and neurosurgical patients requiring external CSF
      drainage due to acute occlusive hydrocephalus. METHODS: Nineteen consecutive
      patients were enrolled in the treatment arm of the study and data were
      prospectively recorded for these patients. The control group consisted of 20
      patients for whom data were retrospectively assessed. CSF samples were drawn at
      least three times a week and routine bacterial cultures and CSF analyses were
      done according to standard protocols. The primary endpoint of the study was the
      occurrence of catheter-associated ventriculitis (CAV) proven by positive CSF
      culture. Secondary endpoints were bacterial colonization of the catheter tip and
      CSF pleocytosis. RESULTS: In 20 control patients, 5 CAVs were microbiologically
      diagnosed. In contrast, no positive CSF cultures were found in the treatment
      group. This difference was statistically significant (P < 0.05). All CAVs
      occurred later than day 10 after catheter placement. Colonization of the catheter
      tip was found in 6 patients in the control group and in 5 patients in the
      treatment group (not significant). CONCLUSIONS: This pilot study indicates that
      EVD catheters impregnated with silver nanoparticles might be a new option for
      preventing CAV in neurocritical care patients, and therefore evaluation in a
      large prospective randomized study is warranted.

PMID- 18320145
TI  - Primary intraventricular hemorrhage: yield of diagnostic angiography and clinical
      outcome.
AB  - INTRODUCTION: Primary intraventricular hemorrhage (IVH), bleeding in the
      ventricular system without a discernable parenchymal component, is a rare
      neurological disorder. To better define the features of primary IVH and the yield
      of diagnostic angiography in this condition, we retrospectively analyzed all
      cases of primary IVH evaluated at a tertiary referral hospital over a 6-year
      period and performed a systematic review of the literature. METHODS: For the
      retrospective case series, all patients with primary IVH admitted to the
      neurovascular service at a single tertiary referral center over a 6-year period
      were identified by screening a departmental database. For the systematic review
      of the literature, all case series of patients with primary IVH diagnosed by
      computed tomography were identified in the Medline database. RESULTS: From the
      systematic review, the majority of patients with spontaneous primary IVH
      presented with headache (69%), nausea/vomiting (53%), and altered mental status
      (66%). Most primary IVH patients had associated hydrocephalus (62%), and about
      one-third required ventricular drainage (34%). Diagnostic cerebral angiography
      was positive for a bleeding source in 56%. The two most common causes identified
      by angiography were arteriovenous malformations (58% of positive angiograms) and
      aneurysms (36% of positive angiograms). Approximately one-third of patients with
      primary IVH do not survive hospital discharge (39%). Patient age and amount of
      IVH independently predicted in-hospital mortality. CONCLUSIONS: Primary IVH is a
      rare form of intracerebral hemorrhage, with varying short-term outcomes that
      depend on patient age and the extent of intraventricular hemorrhage. The yield of
      diagnostic cerebral angiography in the setting of primary IVH is very high. The
      two most common causes of primary IVH identified on angiography are arteriovenous
      malformations and aneurysms. Routine catheter angiography in the setting of
      primary IVH is warranted.

PMID- 18320147
TI  - New evidence.

PMID- 18320146
TI  - The conundrum of hyperuricemia, metabolic syndrome, and renal disease.
AB  - The level of serum uric acid in human has been increasing over the last decades,
      and correlates with an increase prevalence of renal disease and metabolic
      syndrome. Understanding the role of uric acid in these conditions may provide
      clues for preventing the current epidemic of renal disease. Controversy still
      remains if hyperuricemia is simply a consequence or a cause of renal disease
      although epidemiological studies have attempted to resolve this issue. In this
      review, we discuss the clinical and experimental evidence for a causal role of
      hyperuricemia in renal diseases and potential relationships of hyperuricemia with
      metabolic syndrome.

PMID- 18320148
TI  - Completely reversible agranulocytosis in a multiple myeloma patient treated with
      thalidomide-dexamethasone.

PMID- 18320149
TI  - First diagnosis of colorectal or breast cancer and prevalence of atrial
      fibrillation.
AB  - Aim of the present study was to assess the prevalence of atrial fibrillation (AF)
      in patients with two different types of cancer. Recent epidemiologic and clinical
      studies support the hypothesis that AF is promoted and maintained by a broad
      spectrum of modulating factors. A total of 2,339 patients admitted to the Surgery
      Department of "Luigi Sacco Hospital, Milan," over the period 1987-2004 were
      eligible for the study. One thousand three hundred and seventeen patients were
      admitted consecutively with a first diagnosis of colorectal or breast cancer
      (cases). The remaining 1,022 were patients admitted to undergo non-neoplastic
      surgery (controls). Routine pre-surgery electrocardiogram available in patient
      charts was analysed by a cardiologist who was not aware of the present study to
      evaluate the presence of atrial fibrillation or other arrhythmias. Overall, AF
      was present in 3.6% cases and 1.6% controls. This corresponded to at least two
      times higher likelihood of having AF in cases compared to controls. Prevalence of
      AF increased with age both in cases and controls. Our study describes an
      increased prevalence of AF in two different types of cancer. Autonomic,
      endocrine, coagulation, and inflammatory alterations were previously described in
      both AF and cancer, and can provide the physiopathological basis to our clinical
      observation.

PMID- 18320150
TI  - Post-surgical hallux varus. A case report.
AB  - Sometimes a hallux varus occurs as a consequence of the treatment for a hallux
      valgus, determined by an alteration of the balance between the muscolo
      ligamentous structure which crosses the first metatarso-phalangeal joint. This
      complication is poorly tolerated by patients. Various operations have been
      proposed to correct the varus, which includes the bone and the soft tissue. A
      clinical case has been presented which uses a split extensor hallucis longus
      transfer, distally sectioned and made to pass under the deep transverse
      intermetatarsal ligament, used as a pulley, and through a tunnel made in the bone
      at the proximal-lateral base of the proximal phalanx, and then tensioned and
      sutured to its medial side.

PMID- 18320151
TI  - Advances in the diagnosis and immunotherapy for ocular inflammatory disease.
AB  - Significant advances in the diagnosis and therapy for uveitis have been made to
      improve the quality of care for patients with ocular inflammatory diseases. While
      traditional ophthalmic examination techniques, fluorescein angiography, and
      optical coherence tomography continue to play a major role in the evaluation of
      patients with uveitis, the advent of spectral domain optical coherence tomography
      and fundus autofluorescence into clinical practice provides additional
      information about disease processes. Polymerase chain reaction and cytokine
      diagnostics have also continued to play a greater role in the evaluation of
      patients with inflammatory diseases. The biologic agents, a group of medications
      that targets cytokines and other soluble mediators of inflammation, have
      demonstrated promise in targeted immunotherapy for specific uveitic entities.
      Their ophthalmic indications have continued to expand, improving the therapeutic
      armentarium of uveitis specialists.

PMID- 18320152
TI  - In vivo imaging of the immune response in the eye.
AB  - The immune system is governed by dynamic events involving in part direct
      intercellular interactions between an immune cell and other cells or the cell's
      environment. Owing to its unique optical characteristics, the eye offers
      remarkable opportunities for the analysis of the immune system by intravital
      microscopy. In this review, we present a brief overview of the current state of
      knowledge of leukocyte trafficking in each of three anatomically distinct and
      medically important regions of the eye (cornea, iris, retina) as determined by
      the application of intravital microscopy to animal models of disease.
      Additionally, we discuss the use of ocular imaging in patients and volunteers.
      Finally, we examine the future prospects for this field in terms of its potential
      for impacting our understanding of fundamental immunological phenomena.

PMID- 18320153
TI  - [Sepsis therapy: present guidelines and their application].
AB  - Severe sepsis and septic shock have an increasing incidence and unchanged high
      mortality. Early diagnosis is necessary to slow the progression of organ
      dysfunction and improve outcome. Early administration of broad-spectrum
      antimicrobial therapy, early and aggressive hemodynamic therapy, and surgical
      source control are the most promising therapeutic approaches. Norepinephrine is
      the first choice as a vasopressor. Starches for volume resuscitation, intensive
      insulin therapy (aiming at 80-110 mg/dl), and low-dose hydrocortisone are not
      recommended outside randomized trials. Recombinant activated protein C is one
      choice for certain patients. The German Sepsis Competence Network (SepNet) is
      currently investigating other open questions.

PMID- 18320154
TI  - [No ordinary anal fistula...].
AB  - We present the case of a 63 year-old male Swiss patient with chronic diarrhea,
      mucous anal discharge, anal fistula, chronic anal ulceration and history of
      tuberculosis 56 years ago. Imaging and endoscopy was highly suspicious for
      Crohn's Disease, but histology and culture for M. tuberculosis proved tuberculous
      proctitis with perianal involvement and fistulation. The consideration of
      extrapulmonal tuberculosis with its various manifestations is crucial for the
      investigation of chronic abdominal complaints in order to avoid serious
      consequences of tuberculosis treated with immunosuppressive therapy.

PMID- 18320156
TI  - Effects of maternal diet and host quality on oviposition patterns and offspring
      performance in a seed beetle (Coleoptera: Bruchidae).
AB  - In seed beetles, oviposition decisions may influence the offspring phenotype
      because eggs constitute the initial resources available for larval development.
      We tested the effects of host quality variations (small vs. large seeds of the
      host plant Calystegia sepium, Convolvulaceae) on oviposition patterns and
      offspring performance of the seed beetle Megacerus eulophus. We also manipulated
      the maternal diet: high diet quality vs. low diet quality to evaluate possible
      interactive effects of the maternal nutritional environment and host quality on
      oviposition patterns. We further assessed the consequences of egg size variation
      in offspring size. Female M. eulophus fed with high-quality diet (H-diet) laid
      more eggs and lived longer than females fed with low-quality diet (P-diet).
      Fecundity decreased under a low-quality host for both maternal diets. The
      occurrence of maternal environmental effects on egg size plasticity was detected.
      Under conditions of low-quality host, mothers fed with the high-quality diet
      produced bigger eggs in comparison with a high-quality host, whereas females fed
      with the low-quality diet produced smaller ones. Regardless of these differences
      observed in egg size depending on the maternal diet, progeny emerging from small
      seeds (low-quality host) showed a similar performance at emergence. Offspring
      traits were only significantly affected by host quality. Beetles emerging from
      large seeds had greater body weight and length than those reared on small seeds.
      Variations in oviposition patterns in response to host quality are discussed.

PMID- 18320157
TI  - Ethanol concentration in food and body condition affect foraging behavior in
      Egyptian fruit bats (Rousettus aegyptiacus).
AB  - Ethanol occurs in fleshy fruit as a result of sugar fermentation by both
      microorganisms and the plant itself; its concentration [EtOH] increases as fruit
      ripens. At low concentrations, ethanol is a nutrient, whereas at high
      concentrations, it is toxic. We hypothesized that the effects of ethanol on the
      foraging behavior of frugivorous vertebrates depend on its concentration in food
      and the body condition of the forager. We predicted that ethanol stimulates food
      consumption when its concentration is similar to that found in ripe fruit,
      whereas [EtOH] below or above that of ripe fruit has either no effect, or else
      deters foragers, respectively. Moreover, we expected that the amount of food
      ingested on a particular day of feeding influences the toxic effects of ethanol
      on a forager, and consequently shapes its feeding decisions on the following day.
      We therefore predicted that for a food-restricted forager, ethanol-rich food is
      of lower value than ethanol-free food. We used Egyptian fruit bats (Rousettus
      aegyptiacus) as a model to test our hypotheses, and found that ethanol did not
      increase the value of food for the bats. High [EtOH] reduced the value of food
      for well-fed bats. However, for food-restricted bats, there was no difference
      between the value of ethanol-rich and ethanol-free food. Thus, microorganisms,
      via their production of ethanol, may affect the patterns of feeding of seed
      dispersing frugivores. However, these patterns could be modified by the body
      condition of the animals because they might trade-off the costs of intoxication
      against the value of nutrients acquired.

PMID- 18320158
TI  - Aggressive reproductive competition among hopelessly queenless honeybee workers
      triggered by pheromone signaling.
AB  - In the honeybee, Apis mellifera, the queen monopolizes reproduction, while the
      sterile workers cooperate harmoniously in nest maintenance. However, under
      queenless (QL) conditions, cooperation collapses and reproductive competition
      among workers ensues. This is mediated through aggression and worker oviposition,
      as well as shifts in pheromones, from worker to queen-like composition. Many
      studies suggest a dichotomy between conflict resolution through aggression or
      through pheromonal signaling. In this paper, we demonstrate that both phenomena
      comprise essential components of reproductive competition and that pheromone
      signaling actually triggers the onset of aggression. We kept workers as QL groups
      until first aggression was observed and subsequently determined the contestants'
      reproductive status and content of the mandibular (MG) and Dufour's glands (DG).
      In groups in which aggression occurred early, the attacked bee had consistently
      more queen-like pheromone in both the MG and DG, although both contestants had
      undeveloped ovaries. In groups with late aggression, the attacked bee had
      consistently larger oocytes and more queen-like pheromone in the DG, but not the
      MG. We suggest that at early stages of competition, the MG secretion is utilized
      to establish dominance and that the DG provides an honest fertility signal. We
      further argue that it is the higher amount of DG pheromone that triggers
      aggression.

PMID- 18320159
TI  - Mate guarding and territorial aggression vary with breeding synchrony in golden
      whistlers (Pachycephala pectoralis).
AB  - Male paternity assurance behaviour during the female fertile period has been
      widely documented amongst birds. In contrast, how sex-specific behavioural
      strategies vary with local breeding synchrony levels remains largely unknown.
      This is important because, in many species, intra-population patterns of extra
      pair fertilisation rates, and hence cuckoldry risk, are known to vary with the
      number of simultaneously fertile females. Each sex may therefore differ in how
      they behave towards male conspecifics during different degrees of breeding
      synchrony. Here I provide evidence of such sex-specific differences in the golden
      whistler (Pachycephala pectoralis), a species in which within-pair paternity
      assurance is negatively associated with breeding synchrony. Via simulated
      territorial intrusions using decoy males, I show that males, but not females,
      increase levels of aggression to male intruders during periods of low synchrony,
      possibly because cuckoldry risk is greatest during this period. In addition,
      males appear to invest more effort into mate guarding after, but not before,
      territorial intrusions during this period. These inter-sexual differences may
      reflect conflicts in interest between the sexes, with females consistently
      showing interest in males during the fertile period regardless of synchrony
      levels and males investing more resources into expelling intruders when the risk
      of paternity loss is greatest. This study thus provides evidence that males may
      be able to detect variation in breeding synchrony and cuckoldry risk and adjust
      their paternity assurance behaviour accordingly.

PMID- 18320160
TI  - Fertility signals in the bumblebee Bombus terrestris (Hymenoptera: Apidae).
AB  - In eusocial Hymenoptera, queen control over workers is probably inseparable from
      the mechanism of queen recognition. In primitively eusocial bumblebees (Bombus),
      worker reproduction is controlled not only by the presence or absence of a
      dominant queen but also by other dominant workers. Furthermore, it was shown that
      the queen dominance is maintained by pheromonal cues. We investigated whether
      there is a similar odor signal released by egg-laying queens and workers that may
      have a function as a fertility signal. We collected cuticular surface extracts
      from nest-searching and breeding Bombus terrestris queens and workers that were
      characterized by their ovarian stages. In chemical analyses, we identified 61
      compounds consisting of aldehydes, alkanes, alkenes, and fatty acid esters. Nest
      searching queens and all groups of breeding females differed significantly in
      their odor bouquets. Furthermore, workers before the competition point (time
      point of colony development where workers start to develop ovaries and lay eggs)
      differed largely from queens and all other groups of workers. Breeding queens
      showed a unique bouquet of chemical compounds and certain queen-specific
      compounds, and the differences toward workers decrease with an increasing
      development of the workers' ovaries, hinting the presence of a reliable fertility
      signal. Among the worker groups, the smallest differences were found after the
      competition point. Egg-laying females contained higher total amounts of chemical
      compounds and of relative proportions of wax-type esters and aldehydes than nest
      searching queens and workers before the competition point. Therefore, these
      compounds may have a function as a fertility signal present in queens and
      workers.

PMID- 18320161
TI  - Biogeography of diseases: a framework for analysis.
AB  - A growing body of literature offers a framework for understanding geographic and
      ecological distributions of species; a few applications of this framework have
      treated disease transmission systems and their geography. The general framework
      focuses on interactions among abiotic requirements, biotic constraints, and
      dispersal abilities of species as determinants of distributional areas. Disease
      transmission systems have key differences from other sorts of biological
      phenomena: Interactions among species are particularly important, interactions
      may be stable or unstable, abiotic conditions may be relatively less important in
      shaping disease distributions, and dispersal abilities may be quite variable. The
      ways in which these differences may influence disease transmission geography are
      complex; I illustrate their effects by means of worked examples regarding West
      Nile Virus, plague, filoviruses, and yellow fever.

PMID- 18320162
TI  - [Follow-up in uterine fibroid embolization].
AB  - Follow-up controls in patients after uterine fibroid embolization (UFE) should
      monitor clinical improvement of symptoms, document shrinkage of the fibroids,
      exclude malignancies and detect and treat potential complications of the
      intervention.A close cooperation with the referring gynecologist, sufficiently
      and carefully informing the patient about the routine follow-up procedure,
      potential complications and their clinical signs are necessary to fulfill this
      goal.Imaging is usually based on ultrasound imaging but may be supplemented by
      MRI. There are different complications in the early phase after UFE and in the
      later postembolization phase.

PMID- 18320163
TI  - [Radiation dose in computed tomography. Risks and challenges].
AB  - The exponentially growing performance of newer scanner generations has increased
      diagnostic opportunities and utilization of computed tomography. The excellent
      clinical results with CT, however, have to be weighed against a high radiation
      exposure. While radiation exposure with modern scanners is well below the
      diagnostic reference values of the EU for most organ systems, radiation dose for
      retrospectively gated cardiac examinations can be substantially higher: organ
      doses can reach 100 mGy, a dose for which cancer induction been proven. For
      children, the situation may also be critical if scanning parameters are not
      adapted to their smaller size and increased radiation risk: the risk-benefit
      ratio may then no longer favor CT. The application of CT for young patients,
      patients with favorable prognosis and for frequent follow-up examinations will
      increase the radiation risk to the individual and the population. The growth
      rates for CT utilization in Germany are well below those in the United States but
      the increasing number of exams will lead to a substantial increase in population
      dose even if the dose per individual exam can be reduced. The combination of
      optimum scanning parameters, automated dose modulation and dose adaptation to the
      individual patient will help contain radiation dose. Further reduction is
      possible by reducing the number of scan phases, limiting the scan length and
      choosing a lower tube voltage. Most important, however, is the close
      collaboration with referring physicians: scanning technique and choice of imaging
      modality can only be adapted if the clinical question is clearly defined. In the
      light of radiation exposure the critical and knowledgeable use of CT becomes the
      more important the easier it is to request an exam and the better the clinical
      results.

PMID- 18320164
TI  - [Terminology of lower urinary tract dysfunction and coding in the ICD-10-GM
      catalogue].
AB  - The terminology of lower urinary tract dysfunction was recommended by the AWMF
      and the German Society of Urology in 2004. However, there is no transfer of this
      terminology to diagnoses according to the classification of the ICD-10-GM
      catalogue. This catalogue is of major relevance for remuneration of inpatient and
      outpatient treatment in the German diagnosis-related groups (DRG) system. This
      article presents a table showing the correspondence between the current
      terminology and the ICD-10-GM classification. The correct coding can change the
      DRG remuneration by a factor of 2 to 3.

PMID- 18320165
TI  - Association between age at menarche and risk of diabetes in adults: results from
      the EPIC-Norfolk cohort study.
AB  - AIMS/HYPOTHESIS: Earlier age at menarche is associated with increased BMI and
      obesity risk from early childhood through to adulthood. We hypothesised that
      earlier age at menarche would also predict subsequent diabetes risk. METHODS:
      This was a population-based prospective cohort study of 13,308 women, who were
      aged 40 to 75 years between 1993 and 1997 and participating in the Norfolk cohort
      of the European Prospective Investigation into Cancer and Nutrition (EPIC
      Norfolk). We used data on age at menarche and ascertained diabetes incidence to
      2005. RESULTS: There were 734 cases of diabetes (363 incident and 371 prevalent
      cases). Mean age at menarche was lower in women with diabetes than in non
      diabetic women (12.8 vs 13.0 years, p = 0.008). Compared with the earliest
      quintile (menarche at 8-11 years), women in the oldest quintile (menarche at 15
      18 years) had lower BMI (25.5 vs 27.4 kg/m2, p < 0.0001) and a reduced risk of
      diabetes (OR 0.66 [95% CI 0.51-0.86] adjusted for age, family history, physical
      activity, smoking, occupational social class, parity and use of hormonal
      preparations). The association between age at menarche and diabetes was linear
      (adjusted OR 0.91 [95% CI 0.87-0.96] per 1 year later menarche) and appeared to
      be completely mediated by adult BMI or waist circumference (OR 0.98 [95% CI 0.93
      1.03], further adjusted for BMI at age 40-75 years). CONCLUSIONS/INTERPRETATION:
      Earlier age at menarche increases the risk of diabetes in women and this
      association appears to be mediated by increased adiposity. History of earlier
      menarche may help to identify women with increased subsequent risk of diabetes.

PMID- 18320166
TI  - The management of plasma glucose in acute cerebral ischaemia and traumatic brain
      injury: more research needed.

PMID- 18320167
TI  - Hyperglycemia and cerebral glucose in aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE: To determine whether hyperglycemia exerts deleterious effects via
      cerebral energy metabolism and to illuminate the effects of cerebral high/low
      glucose in patients with aneurysmal subarachnoid hemorrhage. DESIGN AND SETTING:
      Prospective, nonrandomized single-center study over a 2-year period in an
      intensive care unit at a primary-level university hospital. PATIENTS: 28
      subarachnoid hemorrhage patients (age 53 +/- 10 years, WFNS grade 2.8 +/- 1.5)
      classified as asymptomatic (n = 5) or symptomatic with acute focal or delayed
      ischemic neurological deficits (n = 23). MEASUREMENTS AND RESULTS: Hyperglycemia
      (> 7.8 mmol/l; >140 mg/dl) was more frequent in symptomatic patients and was
      reflected in higher glycerol concentrations than in asymptomatic patients. In all
      patients a microdialysis catheter was inserted into the tissue at risk;
      dialysates were collected hourly for 10 days. Cerebral low-glucose episodes (0.6
      mmol/l) and high-glucose episodes (>2.6 mmol/l) occurred independently of blood
      glucose levels. During high-glucose episodes cerebral microdialysate levels were
      normal, while cerebral low glucose, occurring more frequently in symptomatic
      patients, was associated with severe cellular distress (increase in
      lactate/pyruvate ratio, glutamate, glycerol) and with unfavorable outcome if
      combined with hyperglycemia. CONCLUSIONS: Although hyperglycemia was more
      frequent in symptomatic patients and associated with high glycerol levels,
      hyperglycemia was not related to cerebral high glucose. It appears that the
      association of adverse outcome with acute-phase hyperglycemia is not mediated by
      cerebral glucose metabolism. Cerebral low glucose was associated with severe
      metabolic distress and may present a target for therapy to improve clinical
      outcome.

PMID- 18320168
TI  - Comparative evaluation of different helmets on patient-ventilator interaction
      during noninvasive ventilation.

PMID- 18320169
TI  - Posterior ankle impingement syndrome caused by malunion of joint depressed type
      calcaneal fracture.
AB  - Late complications after calcaneal fracture usually resulted in lateral heel
      pain. Malunion of joint depressed type calcaneal fracture can result in posterior
      ankle impingement pain. This is caused by the posterior calcaneal bone spike
      formed just behind the posterior calcaneal facet. We describe a technique to
      resect the offending posterior calcaneal bone spike to relieve the posterior
      ankle impingement pain.

PMID- 18320170
TI  - Optimal configuration of arthroscopic sliding knots backed up with multiple half
      hitches.
AB  - The purpose of this biomechanical study was to determine optimized configuration
      of additional half-hitches placed after various arthroscopic sliding knots. Four
      commonly used arthroscopic sliding knots, namely, the Duncan loop, the SMC,
      Weston, and SP knot, were included in this study. All knots were tied with a
      single-hole knot pusher using a knot-tying simulator. After tying a sliding knot,
      it was backed up with zero to four additional reverse half-hitches on alternating
      posts (RHAPs). The first half-hitch was either placed on the same post
      (conventional RHAP; c-RHAP) or on the loop limb of the sliding knot (switched
      RHAP; s-RHAP). Ten knots were tied in each configuration using No. 2 Ethibond or
      No. 1 PDSII sutures. Loop security (loop circumference at 5 N) and knot security
      (highest load to failure at a cross-head displacement of 3 mm) were measured.
      Knot configurations, number of RHAPs, or mode of placement of the first half
      hitch did not make clinically significant effects on loop security for either
      suture type. Using No. 2 Ethibond sutures, SMC, SP, and Weston knots required at
      least three additional half-hitches before knot security plateaued. However, when
      the first half-hitch was switched to the loop limb of the sliding knot, only two
      additional half-hitches (2 s-RHAPs) were required to reach maximum knot security.
      Using No. 1 PDSII sutures, SMC knots needed one additional half-hitch to reach
      maximum knot security, whereas SP and Weston knots required two half-hitches.
      However, SMC, SP and Weston knots with switched first half-hitch only required
      one additional half-hitch (1 s-RHAP) to achieve maximum knot security. This study
      demonstrated that switching the post just after the sliding knot could save one
      half-hitch without compromising knot security. That means that sliding knots with
      2 s-RHAPs for No. 2 Ethibond and 1 s-RHAPs for No. 1 PDSII achieved knot security
      comparable to that of sliding knots with 3 c-RHAPs and with 2 c-RHAPs,
      respectively. The results suggested that the optimized configuration for
      arthroscopic sliding knots required a secure sliding knot, such as, the SMC, SP,
      or Weston knots and 2 s-RHAPs when No. 2 Ethibond or No. 1 PDSII suture materials
      were used considering the unraveling tendency of No. 1 PDSII. Results of the
      current study may be helpful for establishing arthroscopic sliding knot-tying
      routines for best results in clinical practice.

PMID- 18320171
TI  - Different bacterial strategies to degrade taurocholate.
AB  - Aerobic enrichment cultures with taurocholate or alkanesulfonates as sole sources
      of carbon and energy for growth were successful and yielded nine bacterial
      isolates, all of which utilized taurocholate. Growth was complex and involved not
      only many, usually transient, excretion products but also sorption of
      taurocholate and cholate to cells. Three metabolic strategies to dissimilate
      taurocholate were elucidated, all of which involved bile salt hydrolase cleaving
      taurocholate to cholate and taurine. Comamonas testosteroni KF-1 utilized both
      the taurine and the cholate moieties for growth. Pseudomonas spp., e.g. strain
      TAC-K3 and Rhodococcus equi TAC-A1 grew with the cholate moiety and released
      taurine quantitatively. Delftia acidovorans SPH-1 utilized the taurine moiety and
      released cholate.

PMID- 18320172
TI  - Cloning and characterization of the rat free fatty acid receptor GPR120: in vivo
      effect of the natural ligand on GLP-1 secretion and proliferation of pancreatic
      beta cells.
AB  - We have recently found that GPR120, which is abundantly expressed in intestine,
      functions as a receptor for unsaturated long-chain free fatty acids (FFAs) and
      that GPR120 stimulation promotes the secretion of glucagons-like peptide-1 (GLP
      1) in the mouse (Hirasawa et al., Nat Med 11:90-94, 2005). In this study, we
      cloned and characterized rat GPR120 (rGPR120), and then we examined the in vivo
      effects of acute and long-term administration of the natural ligand alpha
      linolenic acid (alpha-LA). The cloned rat GPR120 complimentary DNA had a seven
      transmembrane structure, and a homology comparison of human, mouse, and rat
      GPR120 revealed that the rat GPR120 (rGPR120) shares 85 and 98% sequence identity
      with the human and mouse GPR120 proteins, respectively. The tissue distribution
      and ligand properties of rGPR120 were similar to those of mouse GPR120. In
      addition, alpha-LA provoked a transient increase in [Ca2+]i levels in HEK293
      cells expressing rGPR120. Furthermore, administration of alpha-LA to the rat
      increased plasma GLP-1 levels, and long-term administration of alpha-LA led to
      proliferation of pancreatic beta cells, probably because of the enhanced GLP-1
      secretion. These results show that rat GPR120 is a G-protein-coupled receptor
      whose ligand is a free fatty acid, and it may play an important role in the FFA
      associated physiological responses.

PMID- 18320173
TI  - Isotope dilution quantification of ultratrace gamma-glutamyl-Se
      methylselenocysteine species using HPLC with enhanced ICP-MS detection by
      ultrasonic nebulisation or carbon-loaded plasma.
AB  - A method for the accurate determination of ultratrace selenium species of
      relevance to cancer research, such as gamma-glutamyl-Se-methylselenocysteine
      (gamma-glutamyl-SeMC), using species-specific double isotope dilution analysis
      (IDA) with HPLC-ICP-MS is reported for the first time. The (77)Se-enriched gamma
      glutamyl-SeMC spike was produced in-house by collecting the fraction at the
      retention time of the gamma-glutamyl-SeMC peak from a chromatographed aqueous
      extract of (77)Se-enriched yeast, pooling the collected fractions and freeze
      drying the homogenate. The Se content of this spike was characterised using
      reverse isotope dilution mass spectrometry (IDMS) and the isotopic composition of
      this spike was checked prior to quantification of the natural abundance dipeptide
      species in garlic using speciated IDA. The extraction of the gamma-glutamyl-SeMC
      species in water was performed in a sonication bath for 2 h after adding an
      appropriate quantity of (77)Se-enriched gamma-glutamyl-SeMC to 50 mg of garlic to
      give optimal (78)Se/(77)Se and (82)Se/(77)Se ratios of 1.5 and 0.6, respectively.
      The effect of ultrasonic nebulisation, in comparison with the loading of the ICP
      with carbon (through the addition of methane gas on-line), on the detection of Se
      associated with gamma-glutamyl-SeMC using collision/reaction cell ICP-MS with
      hydrogen as collision gas was investigated. Sensitivity enhancements of
      approximately fourfold and twofold were achieved using USN and methane mixed
      plasma, respectively, in comparison with conventional nebulisation and
      conventional Ar ICP-MS. However, an approximately twofold improvement in the
      detection limit was achieved using both approaches (42 ng kg(-1) for (78)Se using
      peak height measurements). The use of species-specific IDMS enabled
      quantification of the dipeptide species at ng g(-1) levels (603 ng g(-1) Se) in
      the complex food matrix with a relative standard deviation (RSD, n = 4) of 4.5%,
      which was approximately half that obtained using standard addition as a
      confirmatory technique. Furthermore, good agreement was found between the gamma
      glutamyl-SeMC species concentrations obtained using both calibration methods.

PMID- 18320174
TI  - Multivariate curve resolution-alternating least squares (MCR-ALS) applied to
      spectroscopic data from monitoring chemical reactions processes.
AB  - This paper overviews the application of multivariate curve resolution (optimized
      by alternating least squares) to spectroscopic data acquired by monitoring
      chemical reactions and other processes. The goals of the resolution methods and
      the principles for understanding their applications are described. Some of the
      problems arising from these evolving systems and the limitations of the
      multivariate curve resolution methods are also discussed. This article reviews
      most of the applications of multivariate curve resolution applied to reacting
      systems published between January 2000 and June 2007. Some basic papers dated
      before 2000 have also been included.

PMID- 18320175
TI  - Biomolecular structural separations by ion mobility-mass spectrometry.

PMID- 18320176
TI  - The risk of altering soil and sediment samples upon extract preparation for
      analytical and bio-analytical investigations--a review.
AB  - Organic total extracts play an important role in soil and sediment risk
      assessment. Beside a routine application in analytical chemistry, they are used
      in bio-analytical investigations as a "worst-case scenario" or, e.g., in order to
      simulate chronic intoxication, and as samples for effect-directed analysis. While
      theoretically providing highly reliable data and good reproducibility, the whole
      process of sample handling and extract preparation can lead to extracts that
      might fail to accurately represent a toxic potential of their corresponding
      sampling site. This review identifies and discusses the most important possible
      alterations that have the potential to lead to over and, more often,
      underestimation of the effectiveness of extracts. Since incorrect data will
      compromise soil and sediment risk assessment as a whole, results from analytical
      and bio-analytical investigations of extracts demand cautious interpretation.
      Reliability of extract testing grows with reproducibility; experiments should
      therefore be repeated with independent extraction replicates. New or optimized
      extraction procedures should circumvent the issues mentioned here while being
      suitable for routine application.

PMID- 18320177
TI  - Analysis of ancient Greco-Roman cosmetic materials using laser desorption
      ionization and electrospray ionization mass spectrometry.
AB  - Microsamples of pink cosmetic powders from the Greco-Roman period were analyzed
      using two complementary analytical approaches for identification of the colouring
      agents (lake pigments originally manufactured from madder plants with an inert
      binder, usually a metallic salt) present in the samples. The first technique was
      a methanolic acidic extraction of the archaeological samples with an additional
      ethyl acetate extraction of the anthraquinone-type colouring agents which were
      identified using high performance liquid chromatography coupled to electrospray
      ionization with high resolution mass spectrometry (LC-ESI-HRMS), and the second
      was direct analysis of a microsample by laser desorption ionization-mass
      spectrometry (LDI-MS). The latter technique is well suited when the quantity of
      samples is very low. This soft ionization technique enables the detection of very
      small quantities of compounds using the combination of positive and negative-ion
      modes. It was also successfully applied for the direct analysis of some
      laboratory-made reference compounds. However, the presence of lead in one of
      these ancient samples induced a spectral suppression phenomenon. In this case and
      conditional on a sufficient quantity of available sample, the former method is
      better adapted for the characterization of these anthraquinone-type molecules.
      This study also confirmed that purpurin, munjistin, and pseudopurpurin are the
      principal colouring agents present in these ancient cosmetic powders constituted
      from madder plants.

PMID- 18320178
TI  - Development and trends of biosurfactant analysis and purification using
      rhamnolipids as an example.
AB  - During the last few decades, increasing interest in biological surfactants led to
      an intensification of research for the cost-efficient production of
      biosurfactants compared with traditional petrochemical surface-active components.
      The quest for alternative production strains also is associated with new demands
      on biosurfactant analysis. The present paper gives an overview of existing
      analytical methods, based on the example of rhamnolipids. The methods reviewed
      range from simple colorimetric testing to sophisticated chromatographic
      separation coupled with detection systems like mass spectrometry, by means of
      which detailed structural information is obtained. High-performance liquid
      chromatography (HPLC) coupled with mass spectrometry currently presents the most
      precise method for rhamnolipid identification and quantification. Suitable
      approaches to accelerate rhamnolipid quantification for better control of
      biosurfactant production are HPLC analysis directly from culture broth by adding
      an internal standard or Fourier transform infrared attenuated total reflectance
      spectroscopy measurements of culture broth as a possible quasi-online
      quantification method in the future. The search for alternative rhamnolipid
      producing strains makes a structure analysis and constant adaptation of the
      existing quantification methods necessary. Therefore, simple colorimetric tests
      based on whole rhamnolipid content can be useful for strain and medium screening.
      Furthermore, rhamnolipid purification from a fermentation broth will be
      considered depending on the following application.

PMID- 18320179
TI  - Neural correlates of decision making with explicit information about
      probabilities and incentives in elderly healthy subjects.
AB  - Recent functional neuroimaging and lesion studies demonstrate the involvement of
      the orbitofrontal/ventromedial prefrontal cortex as a key structure in decision
      making processes. This region seems to be particularly crucial when contingencies
      between options and consequences are unknown but have to be learned by the use of
      feedback following previous decisions (decision making under ambiguity). However,
      little is known about the neural correlates of decision making under risk
      conditions in which information about probabilities and potential outcomes is
      given. In the present study, we used functional magnetic resonance imaging to
      measure blood-oxygenation-level-dependent (BOLD) responses in 12 subjects during
      a decision making task. This task provided explicit information about
      probabilities and associated potential incentives. The responses were compared to
      BOLD signals in a control condition without information about incentives. In
      contrast to previous decision making studies, we completely removed the outcome
      phase following a decision to exclude the potential influence of feedback
      previously received on current decisions. The results indicate that the
      integration of information about probabilities and incentives leads to
      activations within the dorsolateral prefrontal cortex, the posterior parietal
      lobe, the anterior cingulate and the right lingual gyrus. We assume that this
      pattern of activation is due to the involvement of executive functions, conflict
      detection mechanisms and arithmetic operations during the deliberation phase of
      decisional processes that are based on explicit information.

PMID- 18320180
TI  - Interindividual variability and age-dependency of motor cortical plasticity
      induced by paired associative stimulation.
AB  - Paired associative stimulation (PAS) can increase motor cortical excitability,
      possibly by long-term potentiation (LTP)-like mechanisms. As the capability of
      the cortex for plasticity decreases with age, we were interested here in testing
      interindividual variability and age-dependency of the PAS effect. Motor-evoked
      potentials (MEPs) were recorded from the resting right abductor pollicis brevis
      muscle before and for 30 min after PAS in 27 healthy subjects (22-71 years of
      age). PAS consisted of 225 pairs (rate, 0.25 Hz) of right median nerve
      stimulation followed at an interval equaling the individual N20-latency of the
      median nerve somatosensory-evoked cortical potential plus 2 ms by transcranial
      magnetic stimulation of the hand area of left primary motor cortex (PAS(N20+2)).
      The PAS(N20+2)-induced changes in MEP amplitude (ratio post PAS/pre PAS) were
      highly variable (1.00 +/- 0.07, range 0.36-1.68). Fourteen subjects showed the
      expected LTP-like MEP increase (responders) while 13 subjects showed a long-term
      depression (LTD)-like MEP decrease (non-responders). Responders had a
      significantly lower resting motor threshold (RMT) and minimum stimulus intensity
      to elicit MEPs of 1 mV (MEP(1 mV)) than non-responders. RMT and MEP(1 mV)
      correlated significantly negatively with the PAS(N20+2) effect. The absolute
      PAS(N20+2) effect size irrespective of its direction decreased with age (r = 
      0.57, P = 0.002), i.e., LTP-like and LTD-like plasticity were large in young
      subjects but substantially smaller in elderly subjects. In conclusion, measures
      of motor cortical excitability (RMT, MEP(1 mV)) and age determine direction and
      magnitude of PAS effects in individual subjects.

PMID- 18320181
TI  - Population pharmacokinetics of arbekacin in burn patients.
AB  - The aim of this study was to estimate the pharmacokinetics (PK) of arbekacin in
      burn patients using a population-PK approach. Therapeutic drug monitoring data
      consisting of 126 plasma concentrations (including 17 values that were below the
      quantitation limit) from 47 burn patients were retrospectively analyzed using a
      mixed effect method (NONMEM, ver. 6.0). Covariates, such as burn index, age, sex,
      among others, were tested on the basic one-compartment model. In the basic model,
      positive correlations of body weight (WT) and creatinine clearance (CLcr) on
      total clearance (CL) and volume of distributions (V) were assumed. In the final
      model, V increased with burn index (BI). The final model was: CL(L/h) = 3.18x WT/
      70 + 4.49x CLcr/120; V(L) = 27.5x WT/70 + 0.28x (BI-23.5). Between-subject
      variability in terms of CL and V were 35 and 39%, respectively. The CL of our
      burn patients was significantly greater than that reported in unburned patients,
      and V increased proportionally with increasing BI.

PMID- 18320182
TI  - Tizanidine-induced hypotension in patients with liver cirrhosis.

PMID- 18320183
TI  - Who volunteers for phase I clinical trials? Influences of anxiety, social anxiety
      and depressive symptoms on self-selection and the reporting of adverse events.
AB  - OBJECTIVE: To investigate the influence of anxiety, social anxiety and depressive
      symptoms on the willingness of healthy subjects to volunteer for phase I studies
      and to report adverse events. MATERIALS AND METHODS: A group of healthy subjects
      who had never participated in a clinical trial ("Naive Subjects") were invited to
      participate in a phase I study. All subjects were assessed for trait anxiety
      (State-Trait Anxiety Inventory, STAI-T), social anxiety (Social Avoidance and
      Distress, SAD, and Fear of Negative Evaluation, FNE) and depressive
      symptomatology (Beck Depression Inventory, BDI-II). Subjects who accepted the
      invitation to participate were compared with those who refused. The personality
      traits of a group of "Actual Participants" were examined, and the relation of
      these traits to adverse events reported during participation was evaluated.
      RESULTS: A significant inverse correlation was found between the STAI-T (R = 
      0.203, p < 0.05) and SAD (R = -0.204, p < 0.05) scores and the willingness to
      participate. Naive Subjects who refused the invitation to participate showed
      higher scores on STAI-T (Z = -2.600, p < 0.01) and SAD (Z = -2.524, p < 0.05)
      inventories. Logistic regression using BDI-II, STAI-T, SAD and FNE as covariates
      also showed that the only unique predictors of participation were the STAI-T (p <
      0.05) and SAD (p < 0.01) scores. Significant positive correlations were found
      between trait anxiety and reporting of adverse events. CONCLUSION: Participants
      in phase I studies are a self-selected sample defined by low trait-anxiety and
      social avoidance behaviors. This self-selection bias may affect the study results
      because less anxious subjects tend to report fewer adverse events. The
      characterization of a participant's personality traits may be important in phase
      I studies.

PMID- 18320184
TI  - Use of ACE inhibitors and risk of community-acquired pneumonia: a review.
AB  - BACKGROUND: The administration of angiotensin-converting enzyme (ACE) inhibitors
      has been suggested as an alternative strategy for lowering the risk of community
      acquired pneumonia (CAP) in the elderly, especially in patients with neurological
      and cerebrovascular comorbidity. METHODS: We critically examined the relevant
      data from studies regarding the impact of ACE inhibitors in lowering the risk of
      CAP and/or mortality due to CAP in the elderly. We searched PubMed, Cochrane
      Database, and references of initially retrieved articles, and
      http://clinicaltrials.gov for ongoing trials. RESULTS: We identified 285
      evaluable studies. Fourteen studies met the inclusion criteria and were evaluated
      further, of which seven were prospective studies, two randomized controlled
      trials, and five retrospective studies. Eight of ten studies including patients
      of Asian origin demonstrated a statistical significance in favor of ACE
      inhibitors. On the contrary, only one of five studies including patients of non
      Asian origin demonstrated results in favor of ACE inhibitors. CONCLUSION: The
      available data suggest that ACE inhibitors may contribute to the reduction of the
      risk of CAP. Nevertheless, clinical data are scarce and mainly comprise studies
      including patients of Asian origin. As there seem to be differences regarding the
      genetic polymorphism of ACE among patients of different origins, future studies
      are needed that incorporate relevant genetics data that may help clarify the
      role, if any, of ACE inhibitors in preventing CAP.

PMID- 18320185
TI  - Efficacy and safety of disodium ascorbyl phytostanol phosphates in men with
      moderate dyslipidemia.
AB  - OBJECTIVE: This study investigated the efficacy, safety, tolerability, and
      pharmacokinetics of a novel cholesterol absorption inhibitor, FM-VP4, comprising
      disodium ascorbyl sitostanol phosphate (DASP) and disodium ascorbyl campestanol
      phosphate (DACP). METHODS: In phase 1, 30 men received a single dose of 100, 200,
      400, 800, 1,600, or 2,000 mg FM-VP4 or placebo. In phase 2, 100 men were treated
      with 100, 200, 400, or 800 mg/day of FM-VP4 or placebo for 4 weeks. RESULTS: The
      drug was well tolerated at each single or multiple dose level. After 4 weeks of
      treatment, low-density lipoprotein cholesterol (LDL-C) levels changed by 2.7% in
      the placebo group and by 2.9%, -4.2%, and -4.6% in the 100, 200, and 800 mg/day
      groups, respectively, which was not statistically significant. However, 400
      mg/day of FM-VP4 significantly decreased LDL-C by 6.5% (p=0.02). Phase 1 showed
      that DACP and DASP were absorbed into plasma with a median t(max) of 12 h for
      both components, and clearance was slow with a mean t(1/2lambda) of 57 h. During
      4 weeks of treatment, steady state was reached by approximately 8 days.
      CONCLUSION: This study demonstrated that up to 800 mg/day of FM-VP4 is safe and
      well tolerated for at least 4 weeks. Furthermore, the higher doses significantly
      reduced LDL-C by 7% compared with baseline or by 10% compared with placebo, with
      the maximum effect reached at 400 mg/day.

PMID- 18320186
TI  - Plant/microbe cooperation for electricity generation in a rice paddy field.
AB  - Soils are rich in organics, particularly those that support growth of plants.
      These organics are possible sources of sustainable energy, and a microbial fuel
      cell (MFC) system can potentially be used for this purpose. Here, we report the
      application of an MFC system to electricity generation in a rice paddy field. In
      our system, graphite felt electrodes were used; an anode was set in the rice
      rhizosphere, and a cathode was in the flooded water above the rhizosphere. It was
      observed that electricity generation (as high as 6 mW/m(2), normalized to the
      anode projection area) was sunlight dependent and exhibited circadian
      oscillation. Artificial shading of rice plants in the daytime inhibited the
      electricity generation. In the rhizosphere, rice roots penetrated the anode
      graphite felt where specific bacterial populations occurred. Supplementation to
      the anode region with acetate (one of the major root-exhausted organic compounds)
      enhanced the electricity generation in the dark. These results suggest that the
      paddy-field electricity-generation system was an ecological solar cell in which
      the plant photosynthesis was coupled to the microbial conversion of organics to
      electricity.

PMID- 18320187
TI  - Colonization pattern of plant root and leaf surfaces visualized by use of green
      fluorescent-marked strain of Methylobacterium suomiense and its persistence in
      rhizosphere.
AB  - The localization of bacterial cell, pattern of colonization, and survival of
      Methylobacterium suomiense CBMB120 in the rhizosphere of rice and tomato plants
      were followed by confocal laser scanning, scanning electron microscopy, and
      selective plating. M. suomiense CBMB120 was tagged with green fluorescent protein
      (gfp), and inoculation was carried out through seed source. The results clearly
      showed that the gfp marker is stably inherited and is expressed in planta
      allowing for easy visualization of M. suomiense CBMB120. The colonization
      differed in rice and tomato -- intercellular colonization of surface-sterilized
      root sections was visible in tomato but not in rice. In both rice and tomato, the
      cells were visible in the substomatal chambers of leaves. Furthermore, the strain
      was able to compete with the indigenous microorganisms and persist in the
      rhizosphere of tomato and rice, assessed through dilution plating on selective
      media. The detailed ultra-structural study on the rhizosphere colonization by
      Methylobacterium put forth conclusively that M. suomiense CBMB120 colonize the
      roots and leaf surfaces of the plants studied and is transmitted to the aerial
      plant parts from the seed source.

PMID- 18320188
TI  - Present state and perspective of downstream processing of biologically produced
      1,3-propanediol and 2,3-butanediol.
AB  - 1,3-Propanediol and 2,3-butanediol are two promising chemicals which have a wide
      range of applications and can be biologically produced. The separation of these
      diols from fermentation broth makes more than 50% of the total costs in their
      microbial production. This review summarizes the present state of methods studied
      for the recovery and purification of biologically produced diols, with particular
      emphasis on 1,3-propoanediol. Previous studies on the separation of 1,3
      propanediol primarily include evaporation, distillation, membrane filtration,
      pervaporation, ion exchange chromatography, liquid-liquid extraction, and
      reactive extraction. Main methods for the recovery of 2,3-butanediol include
      steam stripping, pervaporation, and solvent extraction. No single method has
      proved to be simple and efficient, and improvements are especially needed with
      regard to yield, purity, and energy consumption. Perspectives for an improved
      downstream processing of biologically produced diols, especially 1,3-propanediol
      are discussed based on our own experience and recent work. It is argued that
      separation technologies such as aqueous two-phase extraction with short chain
      alcohols, pervaporation, reverse osmosis, and in situ extractive or pervaporative
      fermentations deserve more attention in the future.

PMID- 18320189
TI  - Antibody variable-region sequencing as a method for hybridoma cell-line
      authentication.
AB  - Cross-contamination and misidentification of various cell lines is a widespread
      problem that can lead to spurious scientific conclusions. DNA fingerprinting is a
      powerful identification technique, which can be effectively used for the
      authentication of human cell lines. In contrast to human cancer cell lines,
      little attention has so far been given to establishing authentication practices
      for hybridoma cell lines. Since the majority of hybridomas stem from inbred
      animals, they have high genetic uniformity, which reduces the applicability of
      DNA fingerprinting. In the present study, we propose antibody variable-region
      sequencing as a method of choice for hybridoma cell-line authentication. This
      method focuses on the most diverse characteristic of hybridoma cell lines and
      thereby achieves a very high discriminatory power. The sequencing of light-chain
      variable regions has proven to be especially suitable for routine use because of
      its high success rate. Two other possible authentication methods, random
      amplified polymorphic DNA analysis and two-dimensional gel electrophoresis, were
      also examined. Compared to these and other methods that can be used for
      discrimination between hybridoma cell lines, variable-region sequencing has many
      advantages, most notably those of a very high discriminatory power, insensitivity
      to changes in experimental conditions, simple data analysis, and accessibility to
      most laboratories.

PMID- 18320190
TI  - Deletion of iscR stimulates recombinant clostridial Fe-Fe hydrogenase activity
      and H2-accumulation in Escherichia coli BL21(DE3).
AB  - Proteins that catalyze H2-pathways often contain iron-sulfur (Fe-S) clusters and
      are sensitive to O2. We tested whether deletion of the gene encoding the
      transcriptional negative regulator, IscR, could enhance the ability of
      Escherichia coli BL21 to synthesize active recombinant H2-pathway components and
      stimulate ferredoxin-dependent H2-accumulation in the presence or absence of
      oxygen. Under anoxic conditions, deletion of iscR stimulated recombinant Fe-Fe
      hydrogenase activity threefold, whilst plasmid-based overexpression of the isc
      operon had no effect on hydrogenase activity. After cultivation with 21% (v/v) O2
      in the headspace, no recombinant hydrogenase activity was observed in soluble
      extracts of wild-type BL21, although low levels of activity could be observed in
      the DeltaiscR strain (700-fold lower than anoxic conditions, 180-fold greater
      than the limit of detection). Under closed batch conditions starting with 5%
      (v/v) O2, DeltaiscR strains displayed fivefold greater levels of total
      hydrogenase activity and recombinant ferredoxin-dependent H2-accumulation
      relative to the control strain. In cultures starting with 10% (v/v) O2, H2
      accumulation was stimulated 35-fold relative to the control. DeltaiscR strains
      displayed enhanced synthesis and activity of integral H2-pathway components under
      all tested conditions and enhanced H2-accumulation under partially oxic
      conditions. Deletion of iscR is, therefore, a useful strategy to stimulate H2
      production, particularly if the hydrogenase catalyzes the rate-limiting reaction.

PMID- 18320191
TI  - A phase I pharmacological and biological study of PI-88 and docetaxel in patients
      with advanced malignancies.
AB  - PURPOSE: This study evaluated the safety, toxicity, pharmacological properties
      and biological activity of PI-88, a heparanase endoglycosidase enzyme inhibitor,
      with fixed weekly docetaxel in patients with advanced solid malignancies.
      EXPERIMENTAL DESIGN: This was a phase I study to determine the maximal-tolerated
      dose of escalating doses of PI-88 administered subcutaneously for 4 days per
      week, along with docetaxel 30 mg/m(2) given on days 1, 8, 15 of a 28-day
      schedule. RESULTS: Sixteen patients received a total of 42 courses of therapy. No
      dose-limiting toxicities were observed despite escalation to the highest planned
      dose level of PI-88 (250 mg/day). Frequent minor toxicities included fatigue
      (38%), dysgeusia (28.5%), thrombocytopenia (12%), diarrhea (14%), nausea (12%),
      and emesis (10%) in the 42 courses. No significant bleeding complications were
      observed. One patient developed a positive anti-heparin antibody test/serotonin
      releasing assay with positive anti-platelet factor 4/PI-88 antibodies and grade 1
      thrombocytopenia in cycle 5, and was withdrawn from the study without any
      sequelae. PI-88 plasma concentrations (mirrored by APTT) and urinary elimination
      were linear and dose-proportional. Docetaxel did not alter the pharmacokinetic
      (PK) profile of PI-88, nor did PI-88 affect docetaxel PK. No significant
      relationship was determined between plasma or urine FGF-2, or plasma VEGF levels
      and PI-88 dose/response. Although no objective responses were observed; 9 of the
      15 evaluable patients had stable disease for greater than two cycles of therapy.
      CONCLUSION: PI-88 administered at 250 mg/day for 4 days each week for 3 weeks
      with docetaxel 30 mg/m(2) on days 1, 8 and 15, every 28 days, was determined to
      be the recommended dose level for phase II evaluation. This combination was well
      tolerated without severe toxicities or PK interactions.

PMID- 18320192
TI  - Management of cutaneous vascular complications in systemic scleroderma:
      experience from the German network.
AB  - Major cutaneous vascular complications of systemic sclerosis (SSc) are secondary
      Raynaud's phenomenon (RP) and digital ulcers. Even though SSc is a rare disease,
      timely and appropriate management of its vascular complications is mandatory for
      reducing the rate of major impairment. It should therefore be aware to physicians
      from different specialties. We evaluated the diagnostic and therapeutic approach
      toward secondary RP and ulceration in SSc patients at 28 German clinical centers
      at the time of initiation of the German network for Systemic Scleroderma (DNSS).
      We retrieved data via questionnaires and from the DNSS patient registry.
      Management of RP and ulcerations in SSc were heterogeneous at initiation of the
      network, reflecting a sometimes insufficient use of the diagnostic and
      therapeutic possibilities. As such, (1) calcium channel blockers were the first
      line therapy in most centers; but often in insufficient dosages, and (2) only
      21.2% of patients with acral ulceration had received prostacyclins when recruited
      into the network. The sometimes insufficient care of vascular complications of
      SSc in Germany revealed the need for their standardized management, e.g. within a
      network for SSc and for consensus on a diagnostic or therapeutic algorithm.

PMID- 18320193
TI  - Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties.
AB  - We report the case of coexistence of five autoimmune diseases in a 36-year-old
      woman, who initially developed psoriasis. Several years later, the patient was
      diagnosed with a mixed connective tissue disease and primary biliary cirrhosis
      (PBC). On admission to the Department of Rheumatology and Connective Tissue
      Diseases, the patient fulfilled classification criteria of an overlap syndrome
      systemic lupus erythematosus (SLE) with secondary antiphospholipid
      syndrome/systemic sclerosis (SSc)/Sjogren's syndrome (SS) with coexisting PBC and
      psoriasis. The SLE symptoms included discoid lupus erythematosus, arthritis,
      pancytopenia, antinuclear antibodies and anticardiolipin antibodies. Moreover,
      the patient met the criteria of antiphospholipid syndrome diagnosed based on
      preterm delivery before week 34, and high values of anticardiolipin antibodies
      were found at repeated determinations. The SSc symptoms included sclerodactyly,
      pulmonary fibrosis with pulmonary hypertension and esophageal dysfunction. The SS
      syndrome involved xerostomia, xerophthalmia, the positive Schirmer's test and
      presence of anti-SS antibodies. The literature reports overlap syndromes in
      various combinations; however, the coexistence of five autoimmune diseases is
      extremely rare.

PMID- 18320194
TI  - Expression of a synthetic cry1EC gene for resistance against Spodoptera litura in
      transgenic peanut (Arachis hypogaea L.).
AB  - The tobacco cutworm (Spodoptera litura) is a polyphagous foliage insect and a
      major pest on peanut (Arachis hypogaea L.). S. litura is susceptible to the
      chimeric delta-endotoxin Cry1EC reported earlier. De-embryonated cotyledon
      explants of peanut were transformed using Agrobacterium tumefaciens strain EHA101
      harboring a synthetic cry1EC gene driven by the CaMV 35S promoter. Transgenic
      plants of peanut with a single copy insertion of cry1EC were selected in the T(0)
      generation by Southern blot hybridization. Real-time PCR, Western blot and ELISA
      analysis indicated that expression of the cry1EC gene was higher in single copy
      T(1) plants. Immunoassay showed expression of Cry1EC up to 0.13% of total soluble
      protein in T(1) plants. Leaf feeding bioassay on highly expressing transgenic
      lines showed 100% killing of larvae at the 2(nd) instar stage of S. litura. This
      is the first report of transgenic peanut plants with resistance to S. litura.

PMID- 18320195
TI  - Dark-lumen MR colonography with fecal tagging: a comparison of water enema and
      air methods of colonic distension for detecting colonic neoplasms.
AB  - The purpose was to evaluate MR colonography (MRC) with barium fecal tagging in
      detecting colorectal pathology and to determine how air-based and water-based
      colonic distension influences MRC. We studied 83 patients with high risk of
      colonic neoplasms. All received oral barium sulfate for colonic preparation
      before unenhanced and enhanced T1-weighted gradient-echo MRC using either water
      (n=54) or air (n=29) for colonic distension. Fecal tagging, distension, and
      artifacts were recorded. All patients underwent conventional colonoscopy within 2
      weeks of MRC; the techniques were compared for detection of malignant neoplasms
      and polyps >or=1 cm, 6-9 mm, and <or=5 mm. Fecal tagging was "good" in 76% of the
      colonic segments in water-distended patients and 46% of air-distended patients.
      The degree of distension was "good" in 90.7% of water-distended patients and 44%
      of air-distended patients. Severe artifacts were present in 15% air-distended
      patients and 0.3% of water-distended patients. Both water-distended and air
      distended MRC detected all malignant neoplasms and polyps >or=1 cm, but more air
      distended MRC were excluded for poor quality. MRC with fecal tagging is useful
      for detecting lesions >or=1 cm. Air distension was inferior to water distension
      in most aspects. Water-based colonic distension should be used for barium-tagging
      MRC.

PMID- 18320196
TI  - Nectar intake rate is modulated by changes in sucking pump activity according to
      colony starvation in carpenter ants.
AB  - Dynamics of fluid feeding has been deeply studied in insects. However, the
      ability to vary the nectar-intake rate depending only on the carbohydrate
      deprivation has been clearly demonstrated only in Camponotus mus ants. When
      insect morphometry and fluid properties remain constant, changes in intake rate
      could only be attributed to variations in sucking pump activity. Previous records
      of the electrical activity generated during feeding in C. mus have revealed two
      different signal patterns: the regular (RP, frequencies: 2-5 Hz) and the
      irregular (IP, frequencies: 7-12 Hz). This work studies the mechanism underlying
      food intake-rate modulation in ants by analysing whether these patterns are
      involved. Behaviour and electrical activity generated by ants at different
      starvation levels were analysed during feeding on sucrose solutions. Ants were
      able to modulate the intake rate for a variety of sucrose concentrations (10, 40
      and 60%w/w). The IP only occurred for 60% of solutions and its presence did not
      affect the intake rate. However, during the RP generated under the starved state,
      we found frequencies up to 7.5 Hz. RP frequencies positively correlated with the
      intake-rate for all sucrose concentrations. Hence, intake-rate modulation
      according to sugar deprivation is mainly achieved by the ant's ability to vary
      the pumping frequency.

PMID- 18320197
TI  - Dynamic properties of Drosophila olfactory electroantennograms.
AB  - Time-dependent properties of chemical signals are probably crucially important to
      many animals, but little is known about the dynamics of chemoreceptors.
      Behavioral evidence of dynamic sensitivity includes the control of moth flight by
      pheromone plume structure, and the ability of some blood-sucking insects to
      detect varying concentrations of carbon dioxide, possibly matched to host
      breathing rates. Measurement of chemoreceptor dynamics has been limited by the
      technical challenge of producing controlled, accurate modulation of olfactory and
      gustatory chemical concentrations over suitably wide ranges of amplitude and
      frequency. We used a new servo-controlled laminar flow system, combined with
      photoionization detection of surrogate tracer gas, to characterize
      electroantennograms (EAG) of Drosophila antennae during stimulation with fruit
      odorants or aggregation pheromone in air. Frequency response functions and
      coherence functions measured over a bandwidth of 0-100 Hz were well characterized
      by first-order low-pass linear filter functions. Filter time constant varied over
      almost a tenfold range, and was characteristic for each odorant, indicating that
      several dynamically different chemotransduction mechanisms are present. Pheromone
      response was delayed relative to fruit odors. Amplitude of response, and
      consequently signal-to-noise ratio, also varied consistently with different
      compounds. Accurate dynamic characterization promises to provide important new
      information about chemotransduction and odorant-stimulated behavior.

PMID- 18320198
TI  - A not entirely benign procedure: progression of Parkinson's disease.

PMID- 18320199
TI  - Fusiform aneurysm of the basilar artery presenting as a cerebellopontine angle
      mass.
AB  - It is extremely rare that nonsaccular intracranial aneurysms are located at the
      cerebellopontine angle. A 60-year-old woman presented with dizziness and left
      sided sensorineural hearing loss that had developed gradually for 6 months.
      Magnetic resonance imaging scan and magnetic resonance angiography revealed that
      the basilar artery was ectatic and markedly displaced to the cerebellopontine
      angle. The association between otoneurological findings and radiological findings
      is discussed.

PMID- 18320200
TI  - Temporal breach management in chronic otitis media.
AB  - In a retrospective study performed at the Otolaryngology, Head and Neck Surgery
      Department, Pitie-Salpetriere Hospital, Paris from 1991 to March 2007, we
      determined surgical procedures for the treatment of tegmen breaches in chronic
      otitis media. Forty-two cases were examined: 76% corresponded to chronic otitis
      media with cholesteatoma, and 24% to chronic otitis media without cholesteatoma.
      Twenty-eight cases were operated using a combined approach, eight cases using a
      single suprapetrous approach, and six cases using a transmastoid approach. A
      total of 33% of the cases showed a meningocele or a meningoencephalocele treated
      through either a combined or a suprapetrous approach. No recurrence or
      neural/meningeal infectious involvement was found after a mean time of 43 months
      in the 36 long-term follow-up cases operated through the combined or suprapetrous
      approaches. Two cases included in the study were a loss to follow-up. Three of
      the former cases had already been operated for supracentimetric fissure using
      lower approach. Two out of the six patients operated using lower approach
      presented post surgery cerebrospinal fluid otorrhea. Combined or suprapetrous
      approaches seem to be best adapted to the treatment of supracentimetric or
      recurrent tegmen breaches, as well as to the precise examination and repair of
      meningeal lesions. Treatment for tegmen breach can be achieved in a single
      intervention, even when there is an ongoing infection of the middle ear. The
      mastoid approach should be used only for infracentimetric defects when there is
      no neural/meningeal lesion.

PMID- 18320201
TI  - Acute contraction of the proliferative membrane after an intravitreal injection
      of bevacizumab for advanced retinopathy of prematurity.
AB  - BACKGROUND: Despite the recent reports describing the benefits of the
      intravitreal injection of bevacizumab (IVB) to treat ocular neovascular
      disorders, including retinopathy of prematurity (ROP), the possible adverse
      effects of this therapy must also be described. We report here a case of advanced
      ROP which showed an acute contraction of the proliferative membrane after an
      intravitreal injection of bevacizumab. METHODS: A female infant born at 23 weeks
      of gestation with a birth weight of 598 g was referred to the ophthalmologist at
      4 weeks of age. With funduscopic examinations, broad avascular retinas were found
      in both eyes. Since the ROP had progressed to stage 3, zone 1 with plus disease
      in both eyes, retinal photocoagulation was performed at 10 weeks of age. Despite
      the adequate photocoagulation therapy, the proliferation progressed further, and
      partial tractional retinal detachment (TRD) occurred in the right eye, classified
      as stage 4A with plus disease. After extensive discussion with the parents about
      the risks and benefits of IVB as an alternative therapy, they consented to the
      treatment. Under general anesthesia, an intravitreal injection of 0.4 mg
      bevacizumab was performed at 14 weeks of age. RESULTS: The following day, the
      vascular component of the fibrovascular membrane (FVM) regressed, and acute
      fibrosis occurred. However, the ring-shaped FVM contracted centripetally, which
      caused a deterioration of the TRD. The contraction of the FVM progressed until 7
      days after IVB, and resulted in a funnel-like retinal detachment at the posterior
      retina. The other eye also showed TRD at 19 weeks of age classified as stage 4B,
      which necessitated a vitrectomy. No systemic complications were noted before and
      after the treatment. CONCLUSIONS: IVB is a useful therapy to maintain aggressive
      ROP. However, IVB might cause TRD progression in some specific cases.

PMID- 18320202
TI  - Localized matrix metalloproteinase (MMP)-2 and MMP-9 activity in the rat ventral
      prostate during the first week of postnatal development.
AB  - The initial events in prostatic morphogenesis involve cell proliferation,
      epithelial canalization and outgrowth toward the stroma. We have hypothesized
      that stromal rearrangement takes place at the sites of epithelial growth and
      branching and that this rearrangement involves the action of gelatinases matrix
      metalloproteinase (MMP)-2 and MMP-9. Thus, the purpose of the present study was
      to characterize structural aspects of epithelial growth during the first week of
      postnatal development of the rat ventral prostate and to investigate the
      expression, localization and activity of MMP-2 and MMP-9 during this period by
      histological, ultrastructural and immunocytochemical analysis, in addition to gel
      zymography, in situ zymography and Western blotting. An increasing complexity of
      prostatic architecture was observed within the first postnatal week.
      Concurrently, the stroma became more organized and some cells differentiated into
      smooth muscle cells. Reticulin fibers appeared in a basket-like arrangement
      around both growing tips and epithelial sprouts, associated with a fainter
      staining for laminin. MMP-2 and MMP-9 activities were detected. MMP-2/MMP-9
      expression decreased during the first week. Developing epithelial cords showed
      strong and difuse gelatinolytic activity. This activity coincided with the
      distribution of MMP-2 as determined by immunocytochemistry. On the other hand,
      MMP-9 was rather concentrated at the epithelial tips. These results suggest that
      gelatinolytic activity (with contribution of both MMP-2 and MMP-9) in the
      epithelium and at the epithelium-stroma interface are at least in part
      responsible for the tissue remodeling that allows epithelial growth and its
      projection into the surrounding stroma.

PMID- 18320203
TI  - Autophagy-physiology and pathophysiology.
AB  - "Autophagy" is a highly conserved pathway for degradation, by which wasted
      intracellular macromolecules are delivered to lysosomes, where they are degraded
      into biologically active monomers such as amino acids that are subsequently re
      used to maintain cellular metabolic turnover and homeostasis. Recent genetic
      studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7)
      cannot survive longer than 12 h after birth because of nutrient shortage.
      Moreover, tissue-specific impairment of autophagy in central nervous system
      tissue causes massive loss of neurons, resulting in neurodegeneration, while
      impaired autophagy in liver tissue causes accumulation of wasted organelles,
      leading to hepatomegaly. Although autophagy generally prevents cell death, our
      recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated
      the presence of autophagic neuron death in the hippocampus after neonatal
      hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that
      autophagy is involved in various cellular functions. In this review, we introduce
      physiological and pathophysiological roles of autophagy.

PMID- 18320204
TI  - Organotypical tissue cultures from adult murine colon as an in vitro model of
      intestinal mucosa.
AB  - Together with animal experiments, organotypical cell cultures are important
      models for analyzing cellular interactions of the mucosal epithelium and
      pathogenic mechanisms in the gastrointestinal tract. Here, we introduce a three
      dimensional culture model from the adult mouse colon for cell biological
      investigations in an in vivo-like environment. These explant cultures were
      cultured for up to 2 weeks and maintained typical characteristics of the
      intestinal mucosa, including a high-prismatic epithelium with specific epithelial
      cell-to-cell connections, a basal lamina and various connective tissue cell
      types, as analyzed with immunohistological and electron microscopic methods. The
      function of the epithelium was tested by treating the cultures with
      dexamethasone, which resulted in a strong upregulation of the serum- and
      glucocorticoid-inducible kinase 1 similar to that found in vivo. The culture
      system was investigated in infection experiments with the fungal pathogen Candida
      albicans. Wildtype but not Deltacph1/Deltaefg1-knockout Candida adhered to,
      penetrated and infiltrated the epithelial barrier. The results demonstrate the
      potential usefulness of this intestinal in vitro model for studying epithelial
      cell-cell interactions, cellular signaling and microbiological infections in a
      three-dimensional cell arrangement.

PMID- 18320205
TI  - Call-handlers' working conditions and their subjective experience of work: a
      transversal study.
AB  - OBJECTIVES: The present study sought to describe call-center working conditions
      and call-handlers' subjective experience of their work. METHODS: A transversal
      study was performed in companies followed by the 47 occupational physicians
      taking part. A dedicated questionnaire included one part on working conditions
      (work-station organization, task types, work schedules, and controls) and another
      on the perception of working conditions. Psychosocial risk factors were explored
      by three dimensions of the Karasek questionnaire, decision latitude,
      psychological demands and social support. A descriptive stage characterized the
      population and quantified the frequency of the various types of work
      organization, working conditions and perception. Certain working conditions data
      were crossed with perception data. RESULTS: The total sample comprised 2,130 call
      handlers from around 100 different companies. The population was 71.9% female,
      with a mean age of 32.4 years. The general educational level was high, with 1,443
      (68.2%) of call-handlers having at least 2 years' higher education; 1,937 of the
      workers (91.2%) had permanent work contracts. Some working situations were found
      to be associated with low decision latitude and high psychological demands: i.e.,
      where the schedule (full-time or part-time) was imposed, where the call-handlers
      had not chosen to work in a call-center, or where they received prior warning of
      controls. Moreover, the rate of low decision latitude and high psychological
      demands increased with seniority in the job. The rate of low decision latitude
      increased with the size of the company and was higher when call duration was
      imposed and when the call-handlers handled only incoming calls. The rate of high
      psychological demands was higher when call-handlers handled both incoming and
      outgoing calls. CONCLUSIONS: This study confirmed the high rate of psychosocial
      constraints for call-handlers and identified work situations at risk.

PMID- 18320206
TI  - Dynamic stability control in forward falls: postural corrections after muscle
      fatigue in young and older adults.
AB  - Many studies report that muscle strength loss may alter the human system's
      capacity to generate rapid force for balance corrections after perturbations,
      leading to deficient recovery behaviours. Yet little is known regarding the
      effect of modifications in the neuromuscular system induced by fatigue on dynamic
      stability control during postural perturbations. This study investigates the
      effect of muscle strength decline induced by fatiguing contractions on the
      dynamic stability control of young and older adults during forward falls. Eleven
      young and eleven older male adults had to regain balance after sudden falls
      before and after submaximal fatiguing knee extension-flexion contractions. Young
      subjects had a higher margin of stability than older ones before and after the
      fatiguing task. This reflects their enhanced ability in using mechanisms for
      maintaining dynamic stability (i.e. a greater base of support). The margin of
      stability, the boundary of the base of support and the position of the
      extrapolated centre of mass, remained unaffected by the reduction in muscle
      strength induced by the fatiguing contractions, indicating an appropriate
      adjustment of the motor commands to compensate the deficit in muscle strength.
      Both young and older adults were able to counteract the decreased horizontal
      ground reaction forces after the fatiguing task by flexing their knee to a
      greater extent, leading to similar decreases in the horizontal velocity of centre
      of mass as in the pre fatigue condition. The results demonstrate the ability of
      the central nervous system to rapidly modify the execution of postural
      corrections including mechanisms for maintaining dynamic stability.

PMID- 18320207
TI  - Effect of 5 weeks horizontal bed rest on human muscle thickness and architecture
      of weight bearing and non-weight bearing muscles.
AB  - The aim of the present study was to investigate the changes in thickness,
      fascicle length (L (f)) and pennation angle (theta) of the antigravity
      gastrocnemius medialis (GM) and vastus lateralis (VL) muscles, and the non
      antigravity tibialis anterior (TA) and biceps brachii (BB) muscles measured by
      ultrasonography in ten healthy males (aged 22.3 +/- 2.2 years) in response to 5
      weeks of horizontal bed rest (BR). After BR, muscle thickness decreased by 12.2
      +/- 8.8% (P < 0.05) and 8.0 +/- 9.1% (P < 0.005) in the GM and VL, respectively.
      No changes were observed in the TA and BB muscles. L (f) and theta decreased by
      4.8 +/- 5.0% (P < 0.05) and 14.3 +/- 6.8% (P < 0.005) in the GM and by 5.9 +/-
      5.3% (P < 0.05) and 13.5 +/- 16.2% (P < 0.005) in the VL, again without any
      changes in the TA and BB muscles. The finding that amongst the antigravity
      muscles of the lower limbs, the GM deteriorated to a greater extent than the VL
      is possibly related to the differences in relative load that this muscle normally
      experiences during daily loading. The dissimilar response in antigravity and non
      antigravity muscles to unloading likely reflects differences in loading under
      normal conditions. The significant structural alterations of the GM and VL
      muscles highlight the rapid remodelling of muscle architecture occurring with
      disuse.

PMID- 18320208
TI  - Effects of exercise on leukocyte death: prevention by hydrolyzed whey protein
      enriched with glutamine dipeptide.
AB  - Lymphocyte and neutrophil death induced by exercise and the role of hydrolyzed
      whey protein enriched with glutamine dipeptide (Gln) supplementation was
      investigated. Nine triathletes performed two exhaustive exercise trials with a 1
      week interval in a randomized, double blind, crossover protocol. Thirty minutes
      before treadmill exhaustive exercise at variable speeds in an inclination of 1%
      the subjects ingested 50 g of maltodextrin (placebo) or 50 g of maltodextrin plus
      4 tablets of 700 mg of hydrolyzed whey protein enriched with 175 mg of glutamine
      dipeptide dissolved in 250 mL water. Cell viability, DNA fragmentation,
      mitochondrial transmembrane potential and production of reactive oxygen species
      (ROS) were determined in lymphocytes and neutrophils. Exhaustive exercise
      decreased viable lymphocytes but had no effect on neutrophils. A 2.2-fold
      increase in the proportion of lymphocytes and neutrophils with depolarized
      mitochondria was observed after exhaustive exercise. Supplementation of
      maltodextrin plus Gln (MGln) prevented the loss of lymphocyte membrane integrity
      and the mitochondrial membrane depolarization induced by exercise. Exercise
      caused an increase in ROS production by neutrophils, whereas supplementation of
      MGln had no additional effect. MGln supplementation partially prevented
      lymphocyte apoptosis induced by exhaustive exercise possibly by a protective
      effect on mitochondrial function.

PMID- 18320209
TI  - Effect of hyperthermia on the function of thyroid gland.
AB  - Hyperthermia may be a consequence of environmental conditions, bacterial or viral
      infections and/or thyroid storm. This study investigates the acute effect of body
      temperature elevation on thyroid function and on its scintigraphy studies.
      Thyroid scintigraphy was performed on New Zealand White rabbits weighing
      approximately 3-3.5 kg. Each rabbit was injected with 115 MBq (3.1 mCi)
      technetium-99 m pertechnetate ((99m)Tc pertechnetate). Studies were performed
      using Gamma camera equipped with a low energy, high resolution, pinhole
      collimator interfaced with a computer. Static images were acquired 20 min after
      administration of the radiotracer. Two days later the same protocol was repeated
      for the same rabbit after increasing the body temperature by 2 degrees C. The
      experiment was repeated again after a 2-day interval at 3 degrees C, and then
      after another 2-day interval at 4 degrees C. Plasma free thyroxine (FT(4)), free
      triiodothyronine (FT(3)) and thyroid stimulating hormone (TSH) were measured at
      control and at different hyperthermic temperatures (+2, 3, 4 degrees C). We
      recorded isometric tension of rabbit thyroid artery strips in organ baths during
      stepwise temperature elevation. During hyperthermia the decrease in thyroid
      function and thyroid scintigraphy studies was proportional to body temperature
      elevation. The recording of isometric tension in rabbit thyroid artery strips in
      organ baths showed vasoconstriction during hyperthermia which is proportional to
      the heating temperature. Plasma FT(4) and FT(3) level were decreased while TSH
      levels were not affected by acute fever. Our results indicate that hyperthermia
      causes a transient decrease in thyroid gland function and scintigraphic patterns
      on radionuclide studies. Thus, body temperatures must be measured before
      radionuclide studies in order to ensure that interpretation of data is not
      influenced by hyperthermia.

PMID- 18320210
TI  - Endotoxemia and endotoxin tolerance in patients with ARDS.
AB  - BACKGROUND: The significance of endotoxemia in man is controversial, induces
      cytokine release and stimulates the immune system. Exaggerated cytokine release
      of mononuclear cells was observed in acute lung injury/acute respiratory distress
      syndrome (ALI/ARDS). However, repetitive administration of endotoxin can cause
      tolerance. OBJECTIVE: To investigate endotoxemia, plasma TNFalpha, IL-1beta, IL
      6, the liberation capacity of those cytokines from mononuclear cells after LPS
      challenge (Delta values), and plasma antibodies to endotoxins and alpha-hemolysin
      of Staphylococcus aureus in ALI/ARDS. DESIGN: A prospective clinical study was
      conducted. SETTING: The study was carried out at the University Hospital Ulm,
      Ulm, Germany. SUBJECTS: The respondents were 23 patients with ALI/ARDS.
      INTERVENTIONS: ALI/ARDS was defined according to the American-European Consensus
      Conference on ARDS. Blood was collected periodically. Parameters were measured by
      LAL or ELISA. RESULTS: ARDS (P(a)O(2)/F(i)O(2) < 200) revealed higher endotoxemia
      (0.22-0.46 [0.06-1.15] EU/mL vs 0.05-0.14 [0.02-0.63] EU/mL) than ALI
      (P(a)O(2)/F(i)O(2) > 200) but lower DeltaIL-6 (124-209 [10-1214] pg/mL vs 298-746
      [5-1797] pg/mL), DeltaTNFalpha (50-100 [6-660] pg/mL vs 143-243 [12-2795] pg/mL),
      and DeltaIL-1 (2-3 [0-26] pg/mL vs 2-14 [0-99] pg/mL). Endotoxemia correlated
      negative with P(a)O(2)/F(i)O(2) (r, -0.44 to -0.50). All patients presented
      antibodies to lipopolysaccharides and alpha-hemolysin, but the level did not
      correlate with P(a)O(2)/F(i)O(2). CONCLUSIONS: ALI/ARDS is associated with
      endotoxemia. The more severe the disease, the more intense is endotoxemia but the
      lower is the capacity of mononuclear cells to release cytokines (tolerance).
      Antibodies against Gram-positive and Gram-negative bacteria are detectable in the
      plasma but without relation to P(a)O(2)/F(i)O(2).

PMID- 18320211
TI  - Analysis of POSSUM score and postoperative morbidity in patients with rectal
      cancer undergoing surgery.
AB  - BACKGROUND: The Physiological and Operative Severity Score for the enUmeration of
      Mortality and morbidity (POSSUM) and later modifications (P-POSSUM y CR-POSSUM)
      have been used to predict morbidity and mortality rates among patients with
      rectal cancer undergoing surgery. These calculations need some adjustment,
      however. The aim of this study was to assess the applicability of POSSUM to a
      group of patients with rectal cancer undergoing surgery, analysing surgical
      morbidity by means of several variables. METHODS: between January 1995 and
      December 2004, 273 consecutive patients underwent surgery for rectal cancer.
      Information was gathered about the patients, tumour and therapy. To assess the
      prediction capacity of POSSUM, subgroups for analysis were created according to
      variables related to operative morbidity and mortality. RESULTS: The global
      morbidity rate was 23.6% (31.2% predicted by POSSUM). The mortality rate was 0.7%
      (6.64, 1.95 and 2.08 predicted by POSSUM, P-POSSUM and CR-POSSUM respectively).
      POSSUM predictions may be more accurate for patients younger than 51 years, older
      than 70 years, with low anaesthetic risk (ASA I/II), DUKES stage C and D, surgery
      duration of less than 180 minutes and for those receiving neoadjuvant therapy.
      CONCLUSION: POSSUM is a good instrument to make results between different
      institutions and publication comparable. We found prediction errors for some
      variables related to morbidity. Modifications of surgical variables and
      specifications for neoadjuvant therapy as well as physiological variables
      including life style may improve future prediction of surgical risk. More
      research is needed to identify further potential risk factors for surgical
      complications.

PMID- 18320212
TI  - Vacuolar H(+)-ATPase-an enzyme for all seasons.
AB  - The life of every eukaryotic cell depends on the function of vacuolar H(+)-ATPase
      (V-ATPase). Because of its complexity and its challenging properties, the study
      of this enzyme has lagged behind that of its close relative, F-ATPase. We now
      know that V-ATPase is vital for many more physiological and biochemical processes
      than anticipated when the enzyme was discovered a few decades ago. It plays a
      crucial role in the proper functioning of internal organelles such as vacuoles,
      lysosomes, synaptic vesicles, endosomes, secretory granules, and the Golgi
      apparatus as well as in plasma membrane of several organisms and specific tissues
      and specialized cells. Knowledge of its involvement in several diseases,
      including cancer, has helped to establish the importance of V-ATPase for the
      preservation of life.

PMID- 18320213
TI  - Characterization of spermidine and spermine synthases in Lotus japonicus:
      induction and spatial organization of polyamine biosynthesis in nitrogen fixing
      nodules.
AB  - The biosynthesis of the polyamines spermidine (Spd) and spermine (Spm) from
      putrescine (Put) is catalysed by the consequent action of two
      aminopropyltransferases, spermidine synthase (SPDS EC: 2.5.1.16) and spermine
      synthase (SPMS EC: 2.5.1.22). Two cDNA clones coding for SPDS and SPMS homologues
      in the nitrogen-fixing nodules of the model legume Lotus japonicus were
      identified. Functionality of the encoded polypeptides was confirmed by their
      ability to complement spermidine and spermine deficiencies in yeast. The temporal
      and spatial expression pattern of the respective genes was correlated with the
      accumulation of total polyamines in symbiotic and non-symbiotic organs.
      Expression of both genes was maximal at early stages of nodule development, while
      at later stages the levels of both transcripts declined. Both genes were
      expressed in nodule inner cortical cells, vascular bundles, and central tissue.
      In contrast to gene expression, increasing amounts of Put, Spd, and Spm were
      found to accumulate during nodule development and after maturity. Interestingly,
      nodulated plants exhibited systemic changes in both LjSPDS and LjSPMS transcript
      levels and polyamine content in roots, stem and leaves, in comparison to
      uninoculated plants. These results give new insights into the neglected role of
      polyamines during nodule development and symbiotic nitrogen fixation (SNF).

PMID- 18320214
TI  - Gibberellin-induced formation of tension wood in angiosperm trees.
AB  - After gibberellin had been applied to the vertical stems of four species of
      angiosperm trees for approximately 2 months, we observed eccentric radial growth
      that was due to the enhanced growth rings on the sides of stems to which
      gibberellin had been applied. Moreover, the application of gibberellin resulted
      in the formation of wood fibers in which the thickness of inner layers of cell
      walls was enhanced. These thickened inner layers of cell walls were unlignified
      or only slightly lignified. In addition, cellulose microfibrils on the innermost
      surface of these thickened inner layers of cell walls were oriented parallel or
      nearly parallel to the longitudinal axis of the fibers. Such thickened inner
      layers of cell walls had features similar to those of gelatinous layers in the
      wood fibers of tension wood, which are referred to as gelatinous fibers. Our
      anatomical and histochemical investigations indicate that the application of
      gibberellin can induce the formation of tension wood on vertical stems of
      angiosperm trees in the absence of gravitational stimulus.

PMID- 18320215
TI  - Automatic mode of acquisition of spatial sequences in a serial reaction time
      paradigm.
AB  - In this study, the acquisition of spatial sequences was investigated. It was
      found that the acquisition of spatial sequence order could be acquired under
      strictly automatic conditions, namely, when not being part of the task
      requirement nor when being beneficial to purposive behavior. The results are
      discussed from the perspective of the difference between spatial versus non
      spatial sequence learning.

PMID- 18320216
TI  - Microsaccadic responses in a bimodal oddball task.
AB  - In a visual oddball task the presentation of rare targets induces a prolonged
      microsaccadic inhibition as compared to standards. Here, we replicated this
      effect also in the auditory modality. In addition, although auditory standards
      induced a more limited modulation of microsaccadic frequency as compared to
      visual standards, auditory oddballs induced a prolonged microsaccadic inhibition.
      With bimodal standard stimuli the microsaccadic response was determined by the
      attended modality, resembling that produced by attended unimodal stimuli. The
      present findings support the idea that the microsaccadic response to oddball and
      standard stimuli is partly driven by cognitive mechanisms common to both the
      visual and the auditory modality, and that microsaccades can be used as an
      implicit behavioral measure of ongoing cognitive processes.

PMID- 18320217
TI  - Goal congruency without stimulus congruency in bimanual coordination.
AB  - Two experiments explored the role of stimulus congruency and goal congruency for
      the generation of object-oriented actions with two hands. Participants had to
      place two objects into either parallel or opposite orientations by carrying out
      either symmetrical or asymmetrical forearm rotations. Performance was superior
      when the required object orientations were identical rather than different,
      almost independent of the symmetry of the required arm movements. In extending
      previous research, goal congruency effects ensued even under conditions in which
      congruency of imperative response signals could not have contributed to goal
      congruency effects, either because only a single stimulus was used to indicate
      the required goals in an individual trial (Experiment 1) or such stimuli were
      absent at all (Experiment 2). The results thus confirm the importance of goal
      codes for the reconcilableness of bimanual actions, and rule out accounts in
      terms of stimulus-related processes.

PMID- 18320218
TI  - Incidental learning of abstract rules for non-dominant word orders.
AB  - One way in which adult second language learners may acquire a word order that
      differs from their native language word order is through exposure-based
      incidental learning, but little is known about that process and what constrains
      it. The current studies examine whether a non-dominant word order can be learned
      incidentally, and if so, whether the rule can be generalized to new words not
      previously seen in the non-dominant order. Two studies examined the incidental
      learning of rules underlying the order of nouns and verbs in three-word strings.
      The self-timed reading speeds of native English speakers decreased as a result of
      practice with a non-dominant rule (words ordered either as "verb noun noun" or
      "noun noun verb"). The same pattern of results was also found for new words
      ordered according to the previously encountered rule, suggesting learning
      generalized beyond the specific instances encountered. A second experiment showed
      such rule learning could also occur when the nouns were replaced with
      pronounceable pseudowords. Learning was therefore possible in the absence of any
      pre-existing relationships between the items. Theoretical and educational
      implications are discussed.

PMID- 18320219
TI  - Refinement of strategies for the development of a human cytomegalovirus dense
      body vaccine.
AB  - Development of a vaccine against human cytomegalovirus (HCMV) infection has been
      identified as a high priority goal in biomedical research, yet no vaccine has
      been licensed until now. Recombinant subviral dense bodies (recDB) are a
      promising basis for the establishment of such a vaccine. In this article,
      strategies for the generation of recDB, based on recombination-mediated genetic
      engineering of the 230 kb HCMV DNA genome in E. coli are outlined. Analysis of
      viral mutants that were constructed in this process provided the proof-of
      principle that heterologous antigens can be packaged into recDB and that these
      particles prime CD8 T cell responses against the recombinant antigen upon their
      application to HLA-A2 transgenic mice.

PMID- 18320220
TI  - Etiology of hemolysis in two patients with hepatitis A infection: glucose-6
      phosphate dehydrogenase deficiency or autoimmune hemolytic anemia.
AB  - We report two children with hemolytic anemia during the course of hepatitis A
      infection. On admission, the patients had high blood urea nitrogen, creatinine,
      and uric acid levels, as well as anemia, leucocytosis, and direct and indirect
      hyperbilirubinemia. Both patients had a glucose-6-phosphate dehydrogenase
      deficiency (G6PD) and autoimmune antibodies. They were given vitamin K on
      admission. Inadvertent administration of vitamin K could have been related to an
      acute reduction in hemoglobin concentration. To prevent renal damage,
      plasmapheresis with fresh frozen plasma was done to clear bilirubin and plasma
      hemoglobin. The hyperbilirubinemia responded to plasmapheresis. However, acute
      tubular necrosis complicated the clinical course in one patient, and several
      sessions of hemodialysis were required. In conclusion, intravascular hemolysis
      should be considered in patients with hepatitis A infection, marked
      hyperbilirubinemia, and anemia. Although hepatitis A vaccination is not yet
      recommended for routine administration, high-risk patients, including those with
      a G6PD deficiency, should be vaccinated against hepatitis A.

PMID- 18320221
TI  - What's new in: "genetics in childhood epilepsy".
AB  - In recent years, different mutations in genes that control the excitability of
      neurons have been described in idiopathic childhood epilepsies. Most commonly,
      sodium/potassium channelopathies and GABA-receptor mutations are involved. Major
      progress has been made in the field of idiopathic generalised epilepsies
      associated with febrile seizures (GEFS+). It now is becoming clear that mutations
      should not only be looked for in familial cases, but also in sporadic cases,
      especially in infants and young children with unexplained severe epileptic
      encephalopathies. Many studies also define 'epilepsy susceptibility genes', which
      contribute to one's individual genetic vulnerability to develop epilepsy. It
      should be realized, however, that in the most common idiopathic benign childhood
      epilepsies (benign rolandic and occipital epilepsies), major breakthroughs are
      still awaited. In addition, a better clinical description of the epileptic
      phenotypes is needed to explain more precisely the genotypic and phenotypic
      heterogeneity. Genetic studies are nowadays becoming a necessary diagnostic step
      in the evaluation of idiopathic childhood epilepsies, not only in familial cases,
      but also in sporadic cases.

PMID- 18320222
TI  - Genetic variability of diurnally sub-periodic Wuchereria bancrofti in Nicobarese
      tribe of Nicobar group of Islands, Andaman and Nicobar Islands, India.
AB  - Sub-periodic form of Wuchereria bancrofti occurs in several well-isolated islands
      of Nicobar group of islands of Andaman Nicobar archipelago, India, presenting an
      interesting situation to study the genetic variability of its population.
      Microfilariae collected from 40 microfilaria (mf) carriers residing in eight
      locations on five islands (five carriers from each locality) were studied for
      genetic variability by generating random-amplified polymorphic DNA profiles.
      Phylognetic analysis of the profiles revealed a considerable genetic variability
      among parasite populations of different islands. The Nei's gene diversity between
      populations of 40 individual mf carriers ranged from 0.0218 to 0.2400. It was
      highest (0.24) among the parasite populations of Car Nicobar island and lowest
      (0.0218) among those of Payuha area of Camorta island and Teressa island. The
      dendrogram constructed exhibited four distinct clusters, which are geographically
      localized, and the gene flow between them appears to be influenced by human
      migration pattern.

PMID- 18320223
TI  - Trichobilharzia spp. in natural conditions in Annecy Lake, France.
AB  - Annecy Lake is a well-known focus of human cercarial dermatitis in France.
      Identification of the parasites, however, was not performed in the past. Previous
      studies suspected two species, Trichobilharzia franki and Trichobilharzia
      regenti, based on the presence of parasites in mallards and/or morphological
      identification of snails emitting ocellate furcocercariae. Following a
      standardized molecular approach, we studied snails and furcocercariae and
      compared their haplotypes with those deposited in GenBank. The selected markers
      were the second internal transcribed spacer ITS-2 for the snails and ITS-2 and D2
      domain of the ribosomal DNA for the parasites. Our results confirm the presence
      of T. franki and T. regenti and two probable new species that could be potential
      agents of cercarial dermatitis. All the snails emitting the ocellate
      furcocercariae belong to the same species identified as Radix peregra (=Radix
      ovata = Radix balthica). Parasite-host relationships between species of the genus
      Trichobilharzia and snails of the genus Radix do not seem to be as specific as
      supposed previously.

PMID- 18320224
TI  - Metamicrocotyla macracantha, a polyopisthocotylid gill parasite of the striped
      mullet, Mugil cephalus: population dynamics in South Carolina estuaries.
AB  - In the estuarine system of South Carolina (USA), the striped mullet, Mugil
      cephalus, was found to be parasitized by the polyopisthocotylid monogenean
      Metamicrocotyla macracantha among other gill parasites. Mullet of various ages
      were collected monthly for 1 year from oligohaline, mesohaline, polyhaline, and
      euryhaline localities. The population dynamics of M. macracantha was analyzed
      according to time of year, different salinity levels, and host age and sex. Out
      of the 770 mullet studied, 11.2% were infected (mean, two worms per host).
      Neither prevalence nor mean intensity was correlated with biotic factors.
      However, significant seasonal variation in prevalence was observed, and the worm
      was found more frequently in higher salinities. Mean intensity, however, did not
      change significantly with time of year or salinity. This is the first published
      report of M. macracantha in the South Carolina estuarine system and represents
      the northernmost record for this parasite. Furthermore, the lack of common egg
      bearing individuals and juveniles indicated that this area is likely the northern
      limit of the geographical range of M. macracantha, whose life cycle seems
      restricted to more constant water temperatures than those found at the South
      Carolina latitudes.

PMID- 18320225
TI  - Characterization of a profilin-like protein from Schistosoma japonicum, a
      potential new vaccine candidate.
AB  - The tegumental membrane of platyhelminth parasites is of crucial importance for
      modulation of the host response and parasite survival. A complementary
      deoxyribonucleic acid (cDNA) containing an open reading frame of 390 bp, which
      encodes a profilin-like tegumental protein with a theoretical isoelectric point
      of 6.02 and a molecular weight of 14.42 kDa, had been identified by bioinformatic
      analysis. The coding region of the cDNA was cloned into the prokaryotic
      expression vector pGEX-4T-1 and expressed in Escherichia coli. The purified
      recombinant protein named rSj15 was immunogenic and could elicit a high titer of
      antibody in mice. Western blot analysis revealed that the protein was
      differentially expressed during the different growth stages of Schistosoma
      japonicum. Immunohistochemical analysis localized the protein to the tegument and
      underlying tissue of the S. japonicum adult worm. The rSj15 could induce the
      expressions of IL-12 in the cultured mouse dendritic cell.

PMID- 18320226
TI  - Magnetic separation: a highly effective method for synchronization of cultured
      erythrocytic Plasmodium falciparum.
AB  - The magnetic method has been previously utilized to concentrate Plasmodium
      infected erythrocytes without any significant influence on the viability of the
      parasite. We attempted, in this study, to concentrate and synchronize cultivated
      P. falciparum via the magnetic method. The results of this study showed that the
      magnetic method effectively synchronized and concentrated P. falciparum with
      finer demarcation capacity in the erythrocytic asexual cycle of the parasite than
      currently available synchronization methods. Concentration and synchronization by
      the magnetic method proved most effective when schizonts were dominant.
      Therefore, it proved necessary to enhance the synchronization efficiency of the
      magnetic method by first applying the method currently in use, which renders
      schizonts dominant. Our study also showed that the intrinsic life cycle of
      erythrocytic P. falciparum was slightly longer than 48 h observed in natural
      infection cases, and that the length of the intrinsic life cycles between various
      P. falciparum strains differed slightly.

PMID- 18320227
TI  - Gene expression enhancement mediated by the 5' UTR intron of the rice rubi3 gene
      varied remarkably among tissues in transgenic rice plants.
AB  - Introns are important sequence elements that modulate the expression of genes.
      Using the GUS reporter gene driven by the promoter of the rice (Oryza sativa L.)
      polyubiquitin rubi3 gene, we investigated the effects of the 5' UTR intron of the
      rubi3 gene and the 5' terminal 27 bp of the rubi3 coding sequence on gene
      expression in stably transformed rice plants. While the intron enhanced GUS gene
      expression, the 27-bp fused to the GUS coding sequence further augmented GUS
      expression level, with both varying among different tissues. The intron elevated
      GUS gene expression mainly at mRNA accumulation level, but also stimulated
      enhancement at translational level. The enhancement on mRNA accumulation, as
      determined by realtime quantitative RT-PCR, varied remarkably with tissue type.
      The augmentation by the intron at translational level also differed by tissue
      type, but to a lesser extent. On the other hand, the 27-bp fusion further boosted
      GUS protein yield without affecting mRNA accumulation level, indicating
      stimulation at translation level, which was also affected by tissue type. The
      research revealed substantial variation in the magnitudes of intron-mediated
      enhancement of gene expression (IME) among tissues in rice plants and the
      importance of using transgenic plants for IME studies.

PMID- 18320228
TI  - Aspergillus niger genome-wide analysis reveals a large number of novel alpha
      glucan acting enzymes with unexpected expression profiles.
AB  - The filamentous ascomycete Aspergillus niger is well known for its ability to
      produce a large variety of enzymes for the degradation of plant polysaccharide
      material. A major carbon and energy source for this soil fungus is starch, which
      can be degraded by the concerted action of alpha-amylase, glucoamylase and alpha
      glucosidase enzymes, members of the glycoside hydrolase (GH) families 13, 15 and
      31, respectively. In this study we have combined analysis of the genome sequence
      of A. niger CBS 513.88 with microarray experiments to identify novel enzymes from
      these families and to predict their physiological functions. We have identified
      17 previously unknown family GH13, 15 and 31 enzymes in the A. niger genome, all
      of which have orthologues in other aspergilli. Only two of the newly identified
      enzymes, a putative alpha-glucosidase (AgdB) and an alpha-amylase (AmyC), were
      predicted to play a role in starch degradation. The expression of the majority of
      the genes identified was not induced by maltose as carbon source, and not
      dependent on the presence of AmyR, the transcriptional regulator for starch
      degrading enzymes. The possible physiological functions of the other predicted
      family GH13, GH15 and GH31 enzymes, including intracellular enzymes and cell wall
      associated proteins, in alternative alpha-glucan modifying processes are
      discussed.

PMID- 18320230
TI  - Alteration of sensory abilities regulates the spatial scale of nonlethal predator
      effects.
AB  - Many studies have shown that nonlethal predator effects such as trait-mediated
      interactions (TMIs) can have significant impacts on the structure and function of
      communities, but the role that environmental conditions play in modulating the
      scale and magnitude of these effects has not been carefully investigated. TMIs
      occur when prey exhibit behavioral or physiological responses to predators and
      may be more prevalent when abiotic conditions increase prey reactions to
      consumers. The purpose of this study was to determine if turbulence would alter
      the distance over which prey in aquatic systems respond to chemical cues emitted
      by predators in nature, thus changing the scales over which nonlethal predator
      effects occur. Using hard clams and blue crabs as a model predator-prey system,
      we investigated the effects of turbulence on clam reactive distance to predatory
      blue crabs in the field. Results suggest that turbulence diminishes clam
      reactions to predators and that the environmental context must be considered when
      predicting the extent of indirect predator effects in natural systems.

PMID- 18320229
TI  - Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery:
      new insights on GxE interactions and pathogenic pathways.
AB  - Preterm delivery (PTD, <37 weeks of gestation) is a significant clinical and
      public health problem. Previously, we reported that maternal smoking and
      metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 synergistically increase
      the risk of low birth weight. This study investigates the relationship between
      maternal smoking and metabolic gene polymorphisms of CYP1A1 MspI and GSTT1 with
      preterm delivery (PTD) as a whole and preterm subgroups. This case-control study
      included 1,749 multi-ethnic mothers (571 with PTD and 1,178 controls) enrolled at
      Boston Medical Center. After adjusting covariates, regression analyses were
      performed to identify individual and joint associations of maternal smoking, two
      functional variants of CYP1A1 and GSTT1 with PTD. We observed a moderate effect
      of maternal smoking on PTD (OR = 1.6; 95% CI: 1.1-2.2). We found that compared to
      non-smoking mothers with low-risk genotypes, there was a significant joint
      association of maternal smoking, CYP1A1 (Aa/aa) and GSTT1 (absent) genotypes with
      gestational age (beta = -3.37; SE = 0.86; P = 9 x 10(-5)) and with PTD (OR = 5.8;
      95% CI: 2.0-21.1), respectively. Such joint association was particularly strong
      in certain preterm subgroups, including spontaneous PTD (OR = 8.3; 95% CI: 2.7
      30.6), PTD < 32 weeks (OR = 11.1; 95% CI: 2.9-47.7), and PTD accompanied by
      histologic chorioamnionitis (OR = 15.6; 95% CI: 4.1-76.7). Similar patterns were
      observed across ethnic groups. Taken together, maternal smoking significantly
      increased the risk of PTD among women with high-risk CYP1A1 and GSTT1 genotypes.
      Such joint associations were strongest among PTD accompanied by histologic
      chorioamnionitis.

PMID- 18320231
TI  - Recruitment dynamics in a rainforest seedling community: context-independent
      impact of a keystone consumer.
AB  - The influence of keystone consumers on community structure is frequently context
      dependent; the same species plays a central organising role in some situations,
      but not others. On Christmas Island, in the Indian Ocean, a single species of
      omnivorous land crab, Gecarcoidea natalis, dominates the forest floor across
      intact rainforest. We hypothesised that this consumer plays a key role in
      regulating seedling recruitment and in controlling litter dynamics on the island,
      independent of the type of vegetation in which it occurred. To test this
      hypothesis, we conducted crab exclusion experiments in two forest types on the
      island and followed the dynamics of seedling recruitment and litter processing
      for six years. To determine if these effects were likely to be general across the
      island, we compared land crab densities and seedling abundance and diversity at
      ten sites across island rainforest. Surveys across island rainforest showed that
      seedlings of species susceptible to predation by land crabs are consistently
      rare. Abundance and diversity of these species were negatively correlated to red
      crab abundance. Although red land crabs may be important determinants of seedling
      recruitment to the overstorey, differences in overstorey and seedling composition
      at the sites suggests that recruitment of vulnerable trees still occurs at a
      temporal scale exceeding that of this study. These "windows" of recruitment may
      be related to infrequent events that reduce the effects of land crabs. Our
      results suggest that unlike the context dependence of most keystone consumers in
      continental systems, a single consumer, the red land crab, consistently controls
      the dynamics of seedling recruitment across this island rainforest.

PMID- 18320232
TI  - Clustering hybrid regression: a novel computational approach to study and model
      biohydrogen production through dark fermentation.
AB  - Clustering hybrid regression (CHR) approach was developed and evaluated using
      data from H(2)-producing glucose-based, suspended-cell bioreactor operated for 5
      months. The aim was to describe the relationship between metabolic end products
      and H(2)-production rate. Self-organizing maps (SOM) were used to better
      visualize the dataset and to detect main metabolic patterns in bioprocess data.
      SOM detected three distinct metabolic patterns with butyrate, acetate and ethanol
      as dominant metabolites, respectively. Butyrate dominated metabolism was related
      to high H(2) production, while acetate and ethanol dominated metabolisms resulted
      in low H(2) production. CHR models performed well [mean square error (MSE) 0.55
      and 0.56] in modeling the H(2)-production rate. The results validate the
      suitability of the CHR approach in describing the bioprocess behavior and in the
      modeling of H(2) production rate. The developed model can help in discovering key
      metabolic interactions and suitable process parameters from complex datasets, and
      increase the understanding of the bioprocesses occurring in engineered and
      natural environments.

PMID- 18320233
TI  - Interaction between biofilm development, structure and detachment in rotating
      annular reactors.
AB  - In biotechnology, composition of biofilms and suspended bioaggregates can be
      crucial for system performance or product quality. Consequently, understanding
      biofilm dynamics is important for any process optimisation. The aim of this study
      was to investigate biofilm development and detachment under different
      hydrodynamic conditions and varying glucose load. Confocal laser scanning
      microscopy proved to be a fast method providing information about structure,
      distribution and volume ratio of bacteria and extra cellular polymers (EPS)
      within biofilms and detached biomass. As a result, it could be shown that biofilm
      structure, in terms of density and EPS volume, was largely influenced by
      hydrodynamic conditions. Furthermore, it was demonstrated that the EPS:bacteria
      ratio and distribution was largely influenced by substrate load. Finally, the
      characteristics in biofilm structure and development were reflected in the
      composition and quantity of the detached biomass.

PMID- 18320234
TI  - An effective and simplified pH-stat control strategy for the industrial
      fermentation of vitamin B(12) by Pseudomonas denitrificans.
AB  - In order to improve the productivity of vitamin B(12) by Pseudomonas
      denitrificans carried out in a 120-m(3) fermenter, the effect of pH on vitamin
      B(12) biosynthesis was investigated. Results obtained from shake flask
      experiments showed that the feeding of carbon source (beet molasses or glucose)
      and methyl-group donor (betaine or choline chloride) significantly influenced the
      pH and the biosynthesis of vitamin B(12). In contrast to beet molasses or choline
      chloride, using glucose as a feed medium and betaine as a methyl-group donor, pH
      could be maintained at a stable range. As a result, higher vitamin B(12)
      production was achieved. Accordingly, an effective and simplified pH-stat control
      strategy was established for the fermentation of vitamin B(12) in a 120-m(3)
      industrial fermenter. When the new pH control strategy was applied, pH was stably
      kept in the range of 7.15-7.30 during fermentation. Thus, 214.3 microg/mL of
      vitamin B(12) was achieved.

PMID- 18320235
TI  - Idiopathic mid-aortic syndrome in children.
AB  - Mid-aortic syndrome (MAS) is an uncommon condition characterized by narrowing of
      the abdominal aorta and stenosis of its major branches. Our goal was to
      illustrate the presentation, diagnosis and management of six new cases of
      idiopathic MAS together with 96 cases of idiopathic MAS from the literature. The
      mean age of the 102 cases was 14.3 years (19 days to 49 years). Our patient who
      presented at 19 days of age is the youngest reported to date. Clinical
      presentations included hypertension (94%), claudication (17%), renal failure (4%)
      and intestinal ischemia (1%). Angiography was the diagnostic imaging study of
      choice. Renal arteries were involved in 91% of patients, while the superior
      mesenteric artery and celiac artery were involved in 35%. Thirteen percent of
      cases were managed medically, and the remainder was treated surgically. Our
      experience shows that initial conservative blood pressure management of
      idiopathic MAS is feasible unless medical control of hypertension is
      unsatisfactory, renal function is at risk or there are symptoms of claudication
      or intestinal ischemia. Careful timing and planning of a surgical intervention is
      possible for most cases and may, in select cases, be considered after completion
      of puberty to allow growth to be completed.

PMID- 18320236
TI  - Diabetes and chronic kidney disease: lessons from the Pima Indians.
AB  - Although diabetic nephropathy is a very rare cause of kidney failure during
      childhood, the underlying events leading to progressive kidney injury begin
      during childhood in many patients with type 1 diabetes mellitus (T1DM) and in
      increasing numbers of children with type 2 diabetes mellitus (T2DM). The Pima
      Indians of Arizona represent an exceptionally thoroughly studied population
      suffering from very high rates of T2DM and diabetic nephropathy (T2DN). This
      population well illustrates the often inexorable progression from glomerular
      hyperfiltration to microalbuminuria to overt proteinuria and loss of glomerular
      filtration rate (GFR), paralleled by the accumulation of mesangial matrix and
      basement membrane, glomerular hypertrophy, loss of podocytes and eventual
      glomerular sclerosis and interstitial fibrosis. Structural changes quantitatively
      account for the loss of GFR in T2DN. The mechanism of albuminuria (and its
      relationship to GFR loss) is much less clear. There is strong functional and
      structural evidence for defects in glomerular size-selectivity (shunts) due to
      podocyte pathology, but only beginning at relatively high levels of proteinuria
      (albumin/creatinine ratios > 3000 mg/g). Podocyte loss accompanies, and may
      underlie, the loss of glomeruli to sclerosis. At this point, most evidence in
      humans suggests detachment of intact podocytes from the glomerular basement
      membrane, rather than apoptosis, as the predominant mechanism of podocyte loss.

PMID- 18320237
TI  - Metabonomics of acute kidney injury in children after cardiac surgery.
AB  - Acute kidney injury (AKI) is a major complication in children who undergo
      cardiopulmonary bypass surgery. We performed metabonomic analyses of urine
      samples obtained from 40 children that underwent cardiac surgery for correction
      of congenital cardiac defects. Serial urine samples were obtained from each
      patient prior to surgery and at 4 h and 12 h after surgery. AKI, defined as a 50%
      or greater rise in baseline level of serum creatinine, was noted in 21 children
      at 48-72 h after cardiac surgery. The principal component analysis of liquid
      chromatography/mass spectrometry (LC/MS) negative ionization data of the urine
      samples obtained 4 h and 12 h after surgery from patients who develop AKI
      clustered away from patients who did not develop AKI. The LC/MS peak with mass-to
      charge ratio (m/z) 261.01 and retention time (tR) 4.92 min was further analyzed
      by tandem mass spectrometry (MS/MS) and identified as homovanillic acid sulfate
      (HVA-SO4), a dopamine metabolite. By MS single-reaction monitoring, the
      sensitivity was 0.90 and specificity was 0.95 for a cut-off value of 24 ng/microl
      for HVA-SO4 at 12 h after surgery. We concluded that urinary HVA-SO4 represents a
      novel, sensitive, and predictive early biomarker of AKI after pediatric cardiac
      surgery.

PMID- 18320238
TI  - At the bottom of the differential diagnosis list: unusual causes of pediatric
      hypertension.
AB  - Hypertension affects 1-5% of children and adolescents, and the incidence has been
      increasing in association with obesity. However, secondary causes of hypertension
      such as renal parenchymal diseases, congenital abnormalities and renovascular
      disorders still remain the leading cause of pediatric hypertension, particularly
      in children under 12 years old. Other less common causes of hypertension in
      children and adolescents, including immobilization, burns, illicit and
      prescription drugs, dietary supplements, genetic disorders, and tumors will be
      addressed in this review.

PMID- 18320239
TI  - A "TNM" classification system for cancer pain: the Edmonton Classification System
      for Cancer Pain (ECS-CP).
AB  - OBJECTIVE: The purpose of this paper is to provide an overview of the development
      of a "TNM" cancer pain classification system for advanced cancer patients, the
      Edmonton Classification System for Cancer Pain (ECS-CP). Until we have a common
      international language to discuss cancer pain, understanding differences in
      clinical and research experience in opioid rotation and use remains problematic.
      The complexity of the cancer pain experience presents unique challenges for the
      classification of pain. To date, no universally accepted pain classification
      measure can accurately predict the complexity of pain management, particularly
      for patients with cancer pain that is difficult to treat. MATERIALS AND METHODS:
      In response to this gap in clinical assessment, the Edmonton Staging System
      (ESS), a classification system for cancer pain, was developed. Difficulties in
      definitions and interpretation of some aspects of the ESS restricted acceptance
      and widespread use. RESULT: Construct, inter-rater reliability, and predictive
      validity evidence have contributed to the development of the ECS-CP. The five
      features of the ECS-CP--Pain Mechanism, Incident Pain, Psychological Distress,
      Addictive Behavior and Cognitive Function--have demonstrated value in predicting
      pain management complexity. CONCLUSION: The development of a standardized
      classification system that is comprehensive, prognostic and simple to use could
      provide a common language for clinical management and research of cancer pain. An
      international study to assess the inter-rater reliability and predictive value of
      the ECS-CP is currently in progress.

PMID- 18320240
TI  - Bipolar incompatibility system of an ectomycorrhizal basidiomycete, Rhizopogon
      rubescens.
AB  - The mating systems of most ectomycorrhizal fungi have not been elucidated because
      of two reasons. One is the difficulty of obtaining homokaryotic isolates for
      mating tests caused by the low germination rate of basidiospores, and another is
      the difficulty of checking dikaryotization caused by the absence or inconsistent
      production of clamp connections on heterokaryotic mycelia under laboratory
      conditions. Basidiospore germination of a few ectomycorrhizal fungi has been
      induced by living roots of their host plants. Based on this information, we
      examined methods to obtain homokaryotic isolates of Rhizopogon rubescens using
      its host plant, Pinus thunbergii. The basidiospores of R. rubescens appeared to
      germinate well on an agar plate, on which axenic pine seedlings were grown in
      advance to induce germination, even when the seedlings were removed from the
      plate at the time of spore inoculation. To enhance the production rate of clamp
      connections on the heterokaryotic mycelia of R. rubescens, the culture medium
      composition was modified. The pH of the medium was critical for the production of
      clamp connections, and the optimal pH was higher for the production of clamp
      connections than for mycelial growth. These findings made it possible to conduct
      mating tests, and we found that the mating system of R. rubescens is bipolar with
      a multiallelic mating type factor.

PMID- 18320241
TI  - Cleavage agents for soluble oligomers of human islet amyloid polypeptide.
AB  - Soluble oligomers of human islet amyloid polypeptide (h-IAPP) are implicated in
      the initiation of beta-cell apoptosis leading to type 2 diabetes mellitus (T2DM).
      Cleavage of the h-IAPP included in an oligomer may provide a novel method for
      reducing the level of h-IAPP oligomers, offering a new therapeutic option for
      T2DM. From the combinatorial library of triazine derivatives prepared by
      exploiting the Co(III) complex of cyclen as the cleavage center for peptide
      bonds, eight compounds were selected as cleavage agents for oligomers of h-IAPP.
      After reaction with cleavage agents for 36 h at 37 degrees C and pH 7.50, up to
      20 mol% of h-IAPP (initial concentration: 4.0 microM) was cleaved, although the
      target oligomers existed as transient species. Considerable activity was
      manifested at agent concentrations as low as 100 nM.

PMID- 18320242
TI  - Clinical evaluation of anorganic bovine-derived hydroxyapatite matrix/cell
      binding peptide (P-15) in the treatment of human infrabony defects.
AB  - The purpose of the present study was to compare the clinical outcomes of
      infrabony periodontal defects following treatment with an anorganic bovine
      derived hydroxyapatite matrix/cell-binding peptide (ABM/P-15) flow to open flap
      debridement. Twenty-six patients, each displaying one infrabony defect with
      probing depth>or=6 mm and vertical radiographic bone loss>or=3 mm participated in
      the present study. Patients were allocated randomly to be treated with ABM/P-15
      flow (test group) or open flap debridement (control group). At baseline and at 12
      months after surgery, the following clinical parameters were recorded by a
      blinded examiner: plaque index, gingival index, probing depth (PD), clinical
      attachment level (CAL), and gingival recession. Both treatments resulted in
      significant improvements between baseline and 12 months, in terms of PD reduction
      and CAL gain (p<0.001). At 12 months following therapy, the test group showed a
      reduction in mean PD from 7.8+/-1.6 mm to 3.5+/-1.0 mm and a change in mean CAL
      from 8.5+/-2.1 mm to 4.6+/-1.2 mm, whereas in the control group the mean PD
      decreased from 7.5+/-0.8 mm to 4.9+/-0.7 mm and mean CAL from 8.2+/-1.2 mm to
      6.4+/-1.4 mm. The test group demonstrated significantly greater PD reductions
      (p=0.002) and CAL gains (p=0.001) compared to the control group. In conclusion,
      treatment of infrabony periodontal defects with ABM/P-15 flow significantly
      improved clinical outcomes compared to open flap debridement.

PMID- 18320243
TI  - Learning from others' mistakes in capuchin monkeys (Cebus apella).
AB  - We investigated whether tufted capuchin monkeys (Cebus apella) learn from others'
      mistakes. We prepared three kinds of transparent containers having the same
      appearance: one that could be opened by the lid, one that could be opened from
      the bottom, and one that could be opened either way. Using each of the first two
      one-way-open type containers, the monkeys were trained to copy the human
      demonstrator's action to open the container and obtain a piece of sweet potato
      contained therein. After this training, the demonstrator showed the monkeys an
      action that would open or fail to open the third, two-way-open type container.
      None of the monkeys reliably opened the container by spontaneously compensating
      for the demonstrator's failure (Experiment 1). In Experiment 2, the same subjects
      were trained to correct their own mistakes immediately after failure, before we
      introduced the same test as in Experiment 1. This experience did not result in
      subjects using the demonstrator's failure to produce a successful action. In
      Experiment 3, we placed two monkeys face to face. In this situation, the second
      monkey was presented with the container after the first monkey failed to open it.
      As a result, two capuchin monkeys capitalized on the partner's failure to
      correctly guide his/her behavior. Thus, the monkeys monitored not only the
      outcome of the others' action, but also that action per se. This result suggests
      that not only humans and apes, but also monkeys may understand the meaning of
      others' actions in social learning.

PMID- 18320244
TI  - Molecular epidemiology of Enterobacter cloacae in a neonatal department: a 2-year
      surveillance study.
AB  - A surveillance program was implemented to investigate the molecular epidemiology
      of Enterobacter cloacae in neonatal units. This program ran for 2 years and
      involved screening for E. cloacae intestinal colonization of all infants at
      admission and weekly thereafter. In addition, mothers whose children were
      admitted to neonatal units were also screened. Pulsed-field gel electrophoresis
      analysis was used to establish genetic relationships between strains and to
      identify mother-to-child transmission. During the survey period, 166 (22.6%) of
      the 735 included children had E. cloacae intestinal colonization, and 29 (3.9%)
      patients gave clinical samples positive for E. cloacae. Genotyping revealed 90
      different pulsotypes in the 199 clinical and screening isolates from neonates,
      including three major epidemic clones. Mother-to-child transmission of E. cloacae
      was directly responsible for 8.8% of intestinal colonization of the neonates.
      This surveillance program reveals a major contribution of patient-to-patient
      transmission and the rarity of mother-to-child transmission in the spread of E.
      cloacae in neonates. This highlights the importance of good compliance with
      infection control procedures by health-care workers.

PMID- 18320245
TI  - Lymphadenitis in children is caused by Mycobacterium avium hominissuis and not
      related to 'bird tuberculosis'.
AB  - Mycobacterium avium is the most commonly encountered mycobacterium species among
      non-Mycobacterium tuberculosis complex (nontuberculous mycobacteria) isolates
      worldwide and frequently causes lymphadenitis in children. During a multi-centre
      study in The Netherlands that was performed to determine the optimal treatment
      for mycobacterial lymphadenitis, concern was expressed in the media about the
      possible role of birds as sources of these M. avium infections, referred to as
      'bird tuberculosis.' To examine the involvement of birds in mycobacterial
      lymphadenitis, 34 M. avium isolates from lymphadenitis cases were subjected to
      IS1245 restriction fragment length polymorphism (RFLP) typing. This genotyping
      method enables the distinction of the subspecies M. avium subsp. hominissuis and
      the 'bird-type' M. avium spp. avium. Highly variable RFLP patterns were found
      among the lymphadenitis M. avium isolates, and all belonged to the M. avium
      hominissuis subspecies. A relation to pet birds in the etiology of mycobacterial
      lymphadenitis could not be established, and the source of the infections may be
      environmental.

PMID- 18320246
TI  - A20/AN1 zinc-finger domain-containing proteins in plants and animals represent
      common elements in stress response.
AB  - A20/AN1 zinc-finger domain-containing proteins are well characterized in animals,
      and their role in regulating the immune response is established. Recently, such
      A20/AN1 zinc-finger proteins have been reported from plants. These plant proteins
      are involved in stress response, but their exact molecular mechanism of action is
      yet to be deciphered. Sequence information available in public databases has been
      used to conduct a survey of A20/AN1 zinc-finger proteins across diverse organisms
      with a special emphasis on plants. Domain analysis provides some interesting
      insights into their biological function, the most important being that A20/AN1
      zinc-finger proteins could represent common elements of stress response in plants
      and animals.

PMID- 18320247
TI  - Genome-wide analysis for identification of salt-responsive genes in common wheat.
AB  - To identify salt-responsive genes in wheat, global expression analysis of
      transcripts was carried out using oligo-DNA microarrays. Microarrays have been
      designed from approximately 32,000 unique wheat genes classified from a large
      number of expressed sequence tags (ESTs). Two-week-old seedlings of wheat were
      treated with 150 mM NaCl for 1, 6, and 24 h, and their roots and shoots were
      separately subjected to analyses. Consequently, 5,996 genes showed changes in
      expression of more than twofold and were classified into 12 groups according to
      correlations in expression patterns. These salt-responsive genes were assigned
      functions using the Gene Ontology (GO). Genes assigned to transcription factor,
      transcription-regulator activity, and DNA-binding functions were preferentially
      classified into early response groups. On the other hand, those assigned
      transferase and transporter activity were classified into late response groups.
      These data suggest that multiple signal transduction pathways in response to
      salinity exist in wheat. Transcription factors (TFs) which have been reported as
      participants in salt-tolerant pathway changed their expression levels in response
      to salt treatment. Among them, only a few TFs show high sequence homologies to
      genes in rice. These investigations suggest that salt-responsive genes identified
      by this study are candidates for salt-stress tolerance uniquely in wheat.

PMID- 18320248
TI  - Discovering active compounds from mixture of natural products by data mining
      approach.
AB  - Traditionally, active compounds were discovered from natural products by repeated
      isolation and bioassays, which can be highly time consuming. Here, we have
      developed a data mining approach using the casual discovery algorithm to identify
      active compounds from mixtures by investigating the correlation between their
      chemical composition and bioactivity in the mixtures. The efficacy of our
      algorithm was validated by the cytotoxic effect of Panax ginseng extracts on MCF
      7 cells and compared with previous reports. It was demonstrated that our method
      could successfully pick out active compounds from a mixture in the absence of
      separation processes. It is expected that the presented algorithm can possibly
      accelerate the process of discovering new drugs.

PMID- 18320249
TI  - Alterations in vasomotor control of coronary resistance vessels in remodelled
      myocardium of swine with a recent myocardial infarction.
AB  - The mechanism underlying the progressive deterioration of left ventricular (LV)
      dysfunction after myocardial infarction (MI) towards overt heart failure remains
      incompletely understood, but may involve impairments in coronary blood flow
      regulation within remodelled myocardium leading to intermittent myocardial
      ischemia. Blood flow to the remodelled myocardium is hampered as the coronary
      vasculature does not grow commensurate with the increase in LV mass and because
      extravascular compression of the coronary vasculature is increased. In addition
      to these factors, an increase in coronary vasomotor tone, secondary to
      neurohumoral activation and endothelial dysfunction, could also contribute to the
      impaired myocardial oxygen supply. Consequently, we explored, in a series of
      studies, the alterations in regulation of coronary resistance vessel tone in
      remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate
      that myocardial oxygen balance is perturbed in remodelled myocardium, thereby
      forcing the myocardium to increase its oxygen extraction. These perturbations do
      not appear to be the result of blunted beta-adrenergic or endothelial NO-mediated
      coronary vasodilator influences, and are opposed by an increased vasodilator
      influence through opening of K(ATP) channels. Unexpectedly, we observed that
      despite increased circulating levels of noradrenaline, angiotensin II and
      endothelin-1, alpha-adrenergic tone remained negligible, while the coronary
      vasoconstrictor influences of endogenous endothelin and angiotensin II were
      virtually abolished. We conclude that, early after MI, perturbations in
      myocardial oxygen balance are observed in remodelled myocardium. However,
      adaptive alterations in coronary resistance vessel control, consisting of
      increased vasodilator influences in conjunction with blunted vasoconstrictor
      influences, act to minimize the impairments of myocardial oxygen balance.

PMID- 18320250
TI  - Delayed metabolism of postprandial triglyceride-rich lipoproteins in subjects
      with echolucent carotid plaques.
AB  - Subjects with echolucent carotid plaques have an increased risk of ischemic
      cerebrovascular events independent of degree of stenosis. Low plasma lipoprotein
      lipase (LPL) activity promotes a proatherogenic lipid profile, and delayed
      chylomicron clearance is a risk factor for atherosclerosis. This study was
      conducted to determine plasma LPL activity and postprandial metabolism of
      triglycerides in relation to carotid plaque morphology. Plaque echogenicity was
      assessed by B-mode ultrasound and analysis of the grey scale median (GSM).
      Echolucent plaques were defined as GSM < or = 63 (the median) and echogenic
      plaques as GSM > 63, and 57 subjects with carotid plaques and 38 subjects without
      carotid plaques were recruited. Blood samples were collected before and at 2-h
      interval for 8 h after a standard high fat meal. LPL activity and mass was
      determined before and after heparin administration. Postheparin LPL activity was
      decreased in subjects with echolucent plaques compared to subjects with echogenic
      plaques (P = 0.06) and to controls (P = 0.04). Plaque echogenicity increased
      linearly with increasing levels of postheparin LPL activity (P = 0.02) and mass
      (P = 0.03). Subjects with echolucent plaques had delayed postprandial clearance
      of chylomicron triglycerides compared to controls (P = 0.04). Low postheparin LPL
      activity due to attenuated mobilization of LPL from capillary endothelium may
      play an important role in the formation of echolucent plaques by modulation of
      postprandial lipids and subsequent fat accumulation in the arterial wall.

PMID- 18320251
TI  - SNPs of the FADS gene cluster are associated with polyunsaturated fatty acids in
      a cohort of patients with cardiovascular disease.
AB  - Polymorphisms of the human Delta-5 (FADS1) and Delta-6 (FADS2) desaturase genes
      have been recently described to be associated with the level of several long
      chain n-3 and n-6 polyunsaturated fatty acids (PUFAs) in serum phospholipids. We
      have genotyped 13 single nucleotide polymorphisms (SNPs) located on the FADS1
      FADS2-FADS3 gene cluster (chromosome 11q12-13.1) in 658 Italian adults (78%
      males; mean age 59.7 +/- 11.1 years) participating in the Verona Heart Project.
      Polymorphisms and statistically inferred haplotypes showed a strong association
      with arachidonic acid (C20:4n-6) levels in serum phospholipids and in erythrocyte
      cell membranes (rs174545 adjusted P value for multiple tests, P < 0.0001 and P <
      0.0001, respectively). Other significant associations were observed for linoleic
      (C18:2n-6), alpha-linolenic (C18:3n-3) and eicosadienoic (C20:2n-6) acids. Minor
      allele homozygotes and heterozygotes were associated to higher levels of
      linoleic, alpha-linolenic, eicosadienoic and lower levels of arachidonic acid. No
      significant association was observed for stearidonic (C18:4n-3), eicosapentaenoic
      (C20:5n-3) and docosahexaenoic (C22:6n-3) acids levels. The observed strong
      association of FADS gene polymorphisms with the levels of arachidonic acid, which
      is a precursor of molecules involved in inflammation and immunity processes,
      suggests that SNPs of the FADS1 and FADS2 gene region are worth studying in
      diseases related to inflammatory conditions or alterations in the concentration
      of PUFAs.

PMID- 18320252
TI  - Eicosapentaenoic acid supplementation for chronic hepatitis C patients during
      combination therapy of pegylated interferon alpha-2b and ribavirin.
AB  - Eicosapentaenoic acid (EPA) (1.8 g/day) was administered to 12 chronic hepatitis
      C patients receiving combination therapy of pegylated interferon (PEG-IFN) alpha
      2b and ribavirin for 48 weeks (EPA group). Twelve patients were not administered
      EPA (control group). All patients also received vitamin E and C (300, 600 mg/day,
      respectively) during the therapy. Serum alanine aminotransferase improved to a
      normal level in 8 of 12 patients from the EPA group and 6 of 12 patients from the
      control group after 12 weeks. Lymphocyte counts decreased significantly after 8
      weeks in the control group, but not the EPA group. T-helper (Th) 1 decreased
      after 4 weeks in the control group, but not in the EPA group (two-way ANOVA; P <
      0.05). Th1/Th2 ratios were elevated in 9 of 12 patients in the EPA group, and 3
      out of 12 in the control group (P < 0.05) after 8 weeks. After 12 weeks, the
      arachidonic acid/EPA molar ratio of erythrocyte membrane phospholipid correlated
      negatively with the leukocyte count (n = 24, r = -0.439, P < 0.05) and the
      neutrophil count (n = 24, r = -0.671, P < 0.02). The hemoglobin level improved
      after 48 weeks compared with 24 weeks in only the EPA group. These findings
      suggest that EPA supplementation may be useful in therapy for chronic hepatitis
      C.

PMID- 18320253
TI  - "Genes".
AB  - In order to describe a cell at molecular level, a notion of a "gene" is neither
      necessary nor helpful. It is sufficient to consider the molecules (i.e.,
      chromosomes, transcripts, proteins) and their interactions to describe cellular
      processes. The downside of the resulting high resolution is that it becomes very
      tedious to address features on the organismal and phenotypic levels with a
      language based on molecular terms. Looking for the missing link between
      biological disciplines dealing with different levels of biological organization,
      we suggest to return to the original intent behind the term "gene". To this end,
      we propose to investigate whether a useful notion of "gene" can be constructed
      based on an underlying notion of function, and whether this can serve as the
      necessary link and embed the various distinct gene concepts of biological
      (sub)disciplines in a coherent theoretical framework. In reply to the Genon
      Theory recently put forward by Klaus Scherrer and Jurgen Jost in this journal, we
      shall discuss a general approach to assess a gene definition that should then be
      tested for its expressiveness and potential cross-disciplinary relevance.

PMID- 18320254
TI  - Zeaxanthin is bioavailable from genetically modified zeaxanthin-rich potatoes.
AB  - The carotenoid zeaxanthin accumulates in the human macula lutea and protects
      retinal cells from blue light damage. However, zeaxanthin intake from food
      sources is low. Increasing zeaxanthin in common foods such as potatoes by
      traditional plant breeding or by genetic engineering could contribute to an
      increased intake of this carotenoid and, consequently, to a decreased risk of age
      related macular degeneration. Our aim was to investigate whether zeaxanthin from
      genetically modified zeaxanthin-rich potatoes is bioavailable in humans. Three
      men participated in this randomized, controlled double-blinded, crossover pilot
      study. All subjects consumed 1,100 g of mashed potatoes, either genetically
      modified (Solanum tuberosum L. var. Baltica GM47/18; 3 mg zeaxanthin) or wild
      type control potatoes (Solanum tuberosum L. var. Baltica; 0.14 mg zeaxanthin). A
      second treatment was followed after a 7-day wash-out period. The concentration of
      zeaxanthin was significantly increased in chylomicrons after consumption of
      genetically modified potatoes and 0.27 mg of the 3 mg zeaxanthin dose could be
      detected in chylomicrons. Consumption of control potatoes had no effect on
      concentrations of zeaxanthin in chylomicrons. After normalization of chylomicron
      zeaxanthin for plasma triacylglycerol, the time course of zeaxanthin
      concentrations peaked at 7 h after consumption of genetically modified potatoes.
      There were no significant differences in the concentrations of other major potato
      carotenoids such as lutein and beta-carotene in chylomicrons after consumption of
      genetically modified and wild type control potatoes. Thus, consumption of
      zeaxanthin-rich potatoes significantly increases chylomicron zeaxanthin
      concentrations suggesting that potentially such potatoes could be used as an
      important dietary source of zeaxanthin.

PMID- 18320255
TI  - Orange juice is a good folate source in respect to folate content and stability
      during storage and simulated digestion.
AB  - BACKGROUND: Estimated average folate intake in Sweden is less than 55% of the
      recommended daily intake (RDI) for women of childbearing age (Becker and Pearson
      in Riksmaten 1997-1998 Kostvanor och naringsintag i Sverige. National Food
      Administration, Uppsala, pp 34, 44, 121, 2002). Because a good folate status
      reduces the risk of neural tube defects, mandatory folic acid fortification is
      discussed in some European countries. This however, could lead to exposure to
      unintentionally high amounts of folic acid for some population groups, therefore
      targeted folic acid fortification could be an alternative. AIMS: To (1) determine
      natural folate content in three popular brands of orange juice sold in Sweden,
      (2) determine stability of natural folate and folic acid fortificant during shelf
      life in a folic acid/iron fortified orange juice, (3) determine folate stability
      in four juices during simulated household consumption for one week and (4)
      determine the in vitro bioaccessibility of natural folate in one brand of orange
      juice using the TNO gastroIntestinal Model (TIM). METHODS: Natural folate content
      in juices was determined using RP-HPLC-FL. To determine folic acid content and
      confirm RP-HPLC-FL values LCMS was used. Stability during shelf life was
      determined in unopened bottles of a folic acid/iron fortified juice and for one
      week in four popular juices under household consumption conditions with reopening
      of bottles daily. For an in vitro folate bioaccessibility experiment in orange
      juice the TNO TIM Model was used. RESULTS: 5-CH(3)-H(4)folate was the dominant
      natural folate form in the juices with contents ranging from 16-30 microg/100 g.
      Shelf life losses of folic acid fortificant were 1-4%. During one week simulated
      household consumption 5-CH(3)-H(4)folate content decreased by up to 7% (n.s).
      Bioaccessibility of natural folate in orange juice was almost 100%. Most folate
      was released for absorption in jejunum between 60-120 min after trial start.
      CONCLUSION: Orange juice may be considered a good source of natural folate in
      respect to content and stability during storage and simulated digestion.
      Moreover, added folic acid fortificant in a folic acid/iron fortified orange
      juice was stable during shelf life.

PMID- 18320256
TI  - Serum 1,25-dihydroxy vitamin D is inversely associated with body mass index.
AB  - BACKGROUND: Based on in vitro studies, it has been hypothesized that 1,25
      dihydroxy vitamin D (1,25-vit D) may promote weight gain in humans, but previous
      studies have demonstrated conflicting results regarding the association between
      serum 1,25-vit D and body mass index (BMI). AIM OF THE STUDY: To evaluate the
      relation between serum 1,25-vit D and BMI. METHODS: Two thousand one hundred and
      eighty-seven subjects, recruited from a metabolic and medical lifestyle
      management clinic, were included in a cross-sectional study. BMI, 25-hydroxy
      vitamin D (25-OH-vit D) and 1,25-vit D were measured. The cohort was divided
      according to BMI in five groups (<25, 25-29.9, 30-34.9, 35-39.9 and >39.9
      kg/m(2)). Statistical analyses were performed with multiple linear regression
      models. Age and gender were used as explanatory covariates. RESULTS: With
      increasing BMI group, there was a significant decrease in both serum 25-OH-vit D
      and 1,25-vit D (P<0.001). Those with BMI >39.9 kg/m(2) had 24% lower serum 25-OH
      vit D levels and 18% lower 1,25-vit D levels than those with BMI <25 kg/m(2).
      CONCLUSIONS: There is an inverse association between BMI and the serum levels of
      25-OH-vit D and 1,25-vit D. This makes it highly unlikely that high levels of
      circulating 1,25-vit D contribute to the development of obesity.

PMID- 18320257
TI  - Down-regulation of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde
      decarboxylase by polyunsaturated fatty acids in hepatocytes is not mediated by
      PPARalpha.
AB  - BACKGROUND: alpha-Amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase
      (ACMSD) is a key enzyme in NAD biosynthesis from tryptophan. Dietary
      polyunsaturated fatty acids (PUFA) have been shown to suppress hepatic ACMSD
      activity and its mRNA level in rat. However the mechanism of the suppressive
      action has not been clarified yet. Although the phenomena that fatty acids
      suppress the expression of ACMSD in rat liver have been established in vivo
      experiment, it is still obscure whether the effect of fatty acids on the
      expression of the enzyme is caused by its direct or indirect action, because
      there have been very few investigations performed in vitro. AIM OF THE STUDY: In
      this study, to examine whether down-regulation of ACMSD mRNA by PUFA involves
      peroxisome proliferator-activated receptor (PPAR) alpha mediated mechanism or
      not, we investigated the effect of PUFA on the ACMSD expression by using primary
      cultured rat hepatocytes. METHODS: For this purpose we investigated the effect of
      PUFA (linoleic acid and eicosapentanoic acid) on the ACMSD mRNA level in primary
      cultured rat hepatocytes and compared its effect with that of WY-14,643 (a
      PPARalpha agonist). After the incubation of hepatocytes with fatty acids, WY
      14,643 and/or MK886 (a PPARalpha antagonist), mRNA levels of ACMSD and a
      peroxisome marker enzyme acyl-CoA oxidase (ACO) were determined by competitive
      reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: ACMSD
      mRNA level in primary hepatocytes were decreased by the incubation with high
      concentrations of linoleic acid, eicosapentaenoic acid (EPA) and WY-14,643. The
      appearance of ACO mRNA by WY-14,643 was remarkably increased, and those by
      linoleic acid and EPA were increased less than that by WY-14,643. Moreover, the
      suppression of ACMSD mRNA and the augmentation of ACO mRNA by WY-14,643 were
      inhibited by MK886, but the suppression by PUFA was not substantially affected by
      MK886. CONCLUSIONS: The present study suggesting that the mechanism of decrease
      in ACMSD mRNA level by PUFA was different from that by WY-14,643, and that there
      would be any pathway other than PPARalpha mediated one for PUFA to regulate ACMSD
      expression.

PMID- 18320258
TI  - Bayesian coalescent analysis reveals a high rate of molecular evolution in GB
      virus C.
AB  - GB virus C/hepatitis G (GBV-C) is an RNA virus of the family Flaviviridae.
      Despite replicating with an RNA-dependent RNA polymerase, some previous estimates
      of rates of evolutionary change in GBV-C suggest that it fixes mutations at the
      anomalously low rate of approximately 10(-7) nucleotide substitution per site,
      per year. However, these estimates were largely based on the assumption that GBV
      C and its close relative GBV-A (New World monkey GB viruses) codiverged with
      their primate hosts over millions of years. Herein, we estimated the substitution
      rate of GBV-C using the largest set of dated GBV-C isolates compiled to date and
      a Bayesian coalescent approach that utilizes the year of sampling and so is
      independent of the assumption of codivergence. This revealed a rate of
      evolutionary change approximately four orders of magnitude higher than that
      estimated previously, in the range of 10(-2) to 10(-3) sub/site/year, and hence
      in line with those previously determined for RNA viruses in general and the
      Flaviviridae in particular. In addition, we tested the assumption of host-virus
      codivergence in GBV-A by performing a reconciliation analysis of host and virus
      phylogenies. Strikingly, we found no statistical evidence for host-virus
      codivergence in GBV-A, indicating that substitution rates in the GB viruses
      should not be estimated from host divergence times.

PMID- 18320259
TI  - Complex microsatellite dynamics in the myostatin gene within ruminants.
AB  - A microsatellite has previously been identified in myostatin in cattle.
      Sequencing of this region from other artiodactyls coupled with phylogenetic
      analysis has been used to uncover the potential origins of the microsatellite
      event, which appears either to have been born twice or to have been gained and
      lost within ruminants. While caprids and ovids share the ancestral state with
      pigs and other mammals, microsatellite activity (length polymorphism) is
      uncovered in both deer and bovids. The dynamic process of microsatellite
      evolution, including birth, is discussed here in light of several models.
      Finally, these models are evaluated in the context of patterns of microsatellite
      conservation between closely related mammalian genomes.

PMID- 18320260
TI  - A candidate complex approach to study functional mitochondrial DNA changes:
      sequence variation and quaternary structure modeling of Drosophila simulans
      cytochrome c oxidase.
AB  - A problem with studying evolutionary dynamics of mitochondrial (mt) DNA is that
      classical population genetic techniques cannot identify selected substitutions
      because of genetic hitchhiking. We circumvented this problem by employing a
      candidate complex approach to study sequence variation in cytochrome c oxidase
      (COX) genes within and among three distinct Drosophila simulans mtDNA
      haplogroups. First, we determined sequence variation in complete coding regions
      for all COX mtDNA and nuclear loci and their isoforms. Second, we constructed a
      quaternary structure model of D. simulans COX. Third, we predicted that six of
      nine amino acid changes in D. simulans mtDNA are likely to be functionally
      important. Of these seven, genetic crosses can experimentally determine the
      functional significance of three. Fourth, we identified two single amino acid
      changes and a deletion of two consecutive amino acids in nuclear encoded COX loci
      that are likely to influence cytochrome c oxidase activity. These data show that
      linking population genetics and quaternary structure modeling can lead to
      functional predictions of specific mtDNA amino acid mutations and validate the
      candidate complex approach.

PMID- 18320261
TI  - Rare genomic characters do not support Coelomata: RGC_CAMs.
AB  - Recently there has been a lively debate about a new class of rare genomic
      characters, RGC_CAMs, and their implications for deep bilaterian phylogeny. Most
      recently, nine bilaterian species were analyzed along with subsets of six
      outgroups (Rogozin et al. 2007b), and support for a coelomate clade reported. The
      authors suggested that our previously reported support for an ecdysozoan clade
      (Irimia et al. 2007) reflected (i) one outgroup, Nematostella vectensis, being
      too closely related to bilaterians and (ii) lack of "rigorous statistical
      analysis." Here, we report further studies of these characters. First, we discuss
      general issues of outgroup choice. Second, we point out that an argument used by
      Rogozin et al. against backmutation is not statistically significant. Third, we
      point out that the statistical method of Rogozin et al. fails to incorporate
      backmutations, leading to systematic placement of the long-branch taxon as the
      outgroup. A simple modification of the method yields very different results: 51
      of 63 outgroup combinations favor Ecdysozoa, including 51 of 52 with at least
      eight phylogenetically informative characters, and all 19 with statistically
      significant signal. These results indicate that the Coelomata signal is a long
      branch artifact.

PMID- 18320262
TI  - Solid-phase control on lead bioaccessibility in smelter-impacted soils.
AB  - The goal of this work was to identify the solid-phase control on lead (Pb)
      bioaccessibility in soils impacted by smelter activities in the city of San Luis
      Potosi, in north-central Mexico. Total Pb concentrations in 30 ha of soil terrain
      from a residential area adjacent to the smelter showed levels above the 400-mg/kg
      intervention guideline dictated by Mexican Environmental regulations. These
      concentrations, although raising human health and environmental concerns, showed
      low water-soluble lead (<0.1 mg/L) and relatively low lead bioaccessibility (2.4
      20.5%). X-ray diffraction and electron microscopy techniques showed, in addition
      to common Pb phases reported in similar contaminated environments [galena (PbS)
      and anglesite (PbSO(4))], the presence of a solid lead arsenate phase. The Pb
      solubility measured in soils agrees very well with the low solubility reported
      for the Pb minerals identified and explains the relatively low Pb
      bioaccessibility values measured, presumably from their low dissolution during
      passage through the gastrointestinal tract. The results reported are highly
      relevant for smelter-originated environmental contamination scenarios in general.

PMID- 18320263
TI  - The round-ear incision in full face-lifting.
AB  - Several techniques for face-lifting have been described, all aimed at achieving a
      youthful appearance with a hidden scar. The authors are concerned about the
      conspicuous horizontal scar that travels all the way through the hairless skin
      behind the ears, which they consider very unpleasant and totally unnecessary.
      They are able to achieve a normal-appearing face with a safer technique that
      minimizes the visible scars such as the postauricular one, yet still has good and
      lasting results. In the past 9 years, 202 patients, men and women ages 38 to 86
      years, have undergone surgery using the round-ear face-lifting technique, most of
      them with local anesthesia and sedation. The authors were able to achieve good
      and lasting results with a minimum of complications and to change the unaesthetic
      postauricular scar to a retroauricular one (with contouring of the concha) using
      a new design of marking the skin incisions. A new face-lifting incision is
      described. The procedure is suitable and safer for all patients requiring facial
      rejuvenation. The main advantage of this technique is the absence of visible
      postauricular scars.

PMID- 18320264
TI  - A case of postmastectomy defect reconstructed using a laterothoracic bilaterally
      pedicled v-y advancement flap.
AB  - BACKGROUND: The reconstruction of major defects of the trunk is generally
      achieved by means of pedicled or free musculocutaneous flaps, but for less
      extensive defects, local flaps or skin grafts are currently used. The bilaterally
      pedicled V-Y advancement flap differs from the traditional V-Y advancement flap
      and was described for soft tissue reconstruction in the face. In our unit, the
      bilaterally pedicled V-Y advancement flap is the most used local flap for face
      reconstruction, and our aim was to use it in a different location. METHODS: In
      this case report we present a postmastectomy defect reconstructed with good
      results using the bilaterally pedicled V-Y advancement flap. RESULTS: The flap
      healed without further problems, and a good aesthetic result was obtained.
      CONCLUSION: The bilaterally pedicled V-Y advancement flap is reliable and easy to
      harvest, and not only for face reconstruction. Its versatility and plasticity
      allow its use for the reconstruction of many defects at varying locations.

PMID- 18320265
TI  - Spatial analysis of soil erosion and sediment fluxes: a paired watershed study of
      two Rappahannock River tributaries, Stafford County, Virginia.
AB  - Soil erosion is a serious problem in areas with expanding construction,
      agricultural production, and improper storm water management. It is important to
      understand the major processes affecting sediment delivery to surficial water
      bodies in order to tailor effective mitigation and outreach activities. This
      study analyzes how naturally occurring and anthropogenic influences, such as
      urbanization and soil disturbance on steep slopes, are reflected in the amount of
      soil erosion and sediment delivery within sub-watershed-sized areas. In this
      study, two sub-watersheds of the Rappahannock River, Horsepen Run and Little
      Falls Run, were analyzed using the Revised Universal Soil Loss Equation (RUSLE)
      and a sediment delivery ratio (SDR) to estimate annual sediment flux rates. The
      RUSLE/SDR analyses for Horsepen Run and Little Falls Run predicted 298 Mg/y and
      234 Mg/y, respectively, but nearly identical per-unit-area sediment flux rates of
      0.15 Mg/ha/y and 0.18 Mg/ha/y. Suspended sediment sampling indicated greater
      amounts of sediment in Little Falls Run, which is most likely due to
      anthropogenic influences. Field analyses also suggest that all-terrain vehicle
      crossings represent the majority of sediment flux derived from forested areas of
      Horsepen Run. The combined RUSLE/SDR and field sampling data indicate that small
      scale anthropogenic disturbances (ATV trails and construction sites) play a major
      role in overall sediment flux rates for both basins and that these sites must be
      properly accounted for when evaluating sediment flux rates at a sub-watershed
      scale.

PMID- 18320266
TI  - Iron ore industry emissions as a potential ecological risk factor for tropical
      coastal vegetation.
AB  - In the coastal zone of the Espirito Santo state, Brazil, fragments of restinga,
      which form a natural ecosystem, share their space with an increasing number of
      iron ore industries. The iron ore dust and SO(2) originating from the industry
      processing activities can interfere with the vegetation of the adjacent
      ecosystems at various levels. This study was undertaken in order to evaluate the
      effects of industry emissions on representative members of the restinga flora, by
      measuring physiological and phenological parameters. Foliar samples of Ipomoea
      pes caprae, Canavalia rosea, Sophora tomentosa, and Schinus terebinthifolius were
      collected at three increasing distances from an ore industry (1.0, 5.0, and 15.0
      km), and were assessed for their dust deposition, chlorophyll, and Fe content.
      Phenological monitoring was focused on the formation of shoots, flowers, and
      fruits and was also performed throughout the course of a year. The results showed
      that the edaphic characteristics and the mineral constitutions of the plants were
      affected by industry emissions. In addition, the chlorophyll content of the four
      species increased with proximity to the industry. Phenological data revealed that
      the reproductive effort, as measured by fruit production, was affected by
      emissions and S. tomentosa was the most affected species. The use of an
      integrative approach that combines biochemical and ecological data indicates that
      the restinga flora is under stress due to industry emissions, which on a long
      term basis may put the ecosystem at risk.

PMID- 18320267
TI  - Increasing access to surgical services for the poor in rural Haiti: surgery as a
      public good for public health.
AB  - Although surgical care has not been seen as a priority in the international
      public health community, surgical disease constitutes a significant portion of
      the global burden of disease and must urgently be addressed. The experience of
      the nongovernmental organizations Partners In Health (PIH) and Zanmi Lasante (ZL)
      in Haiti demonstrates the potential for success of a surgical program in a rural,
      resource-poor area when services are provided through the public sector,
      integrated with primary health care services, and provided free of charge to
      patients who cannot pay. Providing surgical care in resource-constrained settings
      is an issue of global health equity and must be featured in national and
      international discussions on the improvement of global health. There are numerous
      training, funding, and programmatic considerations, several of which are raised
      by considering the data from Haiti presented here.

PMID- 18320268
TI  - What is a surgical complication?

PMID- 18320270
TI  - Standing waves of hepatic artery associated with renal and extrarenal
      fibromuscular dysplasia.

PMID- 18320271
TI  - Microcatheter use for difficult percutaneous biliary procedures.
AB  - Percutaneous biliary drainage procedures in patients with nondilated ducts are
      demanding, resulting in lower success rates than in patients with bile duct
      dilatation. Pertinent clinical settings include patients with iatrogenic bile
      leaks, diffuse cholangiocarcinomas, and sclerosing cholangitis. We describe a
      method to facilitate these procedures with the combined use of a 2.7-Fr
      microcatheter and a 0.018-in. hydrophilic wire.

PMID- 18320272
TI  - Inhibition of quorum sensing in Serratia marcescens H30 by molecular regulation.
AB  - Quorum sensing in Serratia marcescens, which uses two types of signaling
      molecules-N-acyl homoserine lactones and furanosyl borate diester-play important
      regulatory roles in the synthesis of 2,3-butanediol and prodigiosin. In the hope
      of understanding the effect of quorum sensing on physiologic metabolism, we
      established two molecular strategies, one to express acyl-homoserine lactone
      hydrolase to inactivate AI-1 signaling molecule using an expression vector with
      lactose as the inducer and the other to mutate luxS gene with a suicide plasmid
      pUTKm2 to inhibit the synthesis of AI-2 signaling molecule.

PMID- 18320273
TI  - Aminoglycoside-resistance mechanisms in multidrug-resistant Staphylococcus aureus
      clinical isolates.
AB  - Aminoglycoside resistance in six clinically isolated Staphylococcus aureus was
      evaluated. Genotypical examination revealed that three isolates (HLGR-10, HLGR
      12, and MSSA-21) have aminoglycoside-modifying enzyme (AME) coding genes and
      another three (GRSA-2, GRSA-4, and GRSA-6) lacked these genes in their genome.
      Whereas isolates HLGR-10 and HLGR-14 possessed bifunctional AME coding gene
      aac(6')-aph(2''), and aph(3')-III and showed high-level resistance to gentamycin
      and streptomycin, MSSA-21 possessed aph(3')-III and exhibited low resistance to
      gentamycin, streptomycin, and kanamycin. The remaining three isolates (GRSA-2,
      GRSA-4, and GRSA-6) exhibited low resistance to all the aminoglycosides because
      they lack aminoglycoside-modifying enzyme coding genes in their genome. The
      transmission electron microscopy of the three isolates revealed changes in cell
      size, shape, and septa formation, supporting the view that the phenomenon of
      adaptive resistance is operative in these isolates.

PMID- 18320277
TI  - New technique for the retraction of the liver in laparoscopic gastrectomy.
AB  - We developed a new technique for the retraction of the liver using a Penrose
      drain and a J-shaped retractor, which is both an easy and time-saving method that
      provides a good view during laparoscopic gastrectomy without damaging the liver.

PMID- 18320278
TI  - Thoracoscopic esophageal mobilization during minimally invasive esophagectomy: a
      head-to-head comparison of prone versus decubitus positions.
AB  - BACKGROUND: Minimally invasive esophagectomy (MIE) is being performed at an
      increasing number of institutions. The thoracoscopic portion is generally
      performed in the left lateral decubitus position. Recently there has been
      increasing interest in esophageal mobilization in the prone position and the
      potential benefits of this technique with regard to operative time, surgeon
      ergonomics, and operative exposure. We sought to objectively compare
      thoracoscopic mobilization of the esophagus in the left lateral decubitus
      position versus the prone position and identify potential differences between the
      two techniques. METHODS: A retrospective review of a prospectively maintained
      esophagectomy database identified 44 patients undergoing MIE during a 20-month
      period (June 2005-February 2007). Of these, 32 patients underwent thoracoscopic
      esophageal mobilization with cervical esophagogastric anastomosis. Eleven cases
      were performed in the left lateral decubitus position and 21 performed in the
      prone position. RESULTS: The patients were comparable in age, tumor stage, and
      fraction undergoing neoadjuvant therapy. There was no statistically significant
      difference between decubitus position and prone position with regard to number of
      lymph nodes procured (14.6 versus 15.5, p = 0.69), complications (6/11 versus
      10/21, p = 1.0), length of stay (9 versus 10 days, p = 1.0), or intraoperative
      blood loss (85 versus 65 cc, p = 0.14). Thoracoscopic operative times were
      significantly shorter in the prone group than the decubitus group (86 versus 123
      min, p = 0.0001). CONCLUSIONS: Prone thoracoscopic esophageal mobilization
      appears to be equivalent to decubitus thoracoscopic esophageal mobilization with
      respect to blood loss, number of lymph nodes dissected, and complications, but
      with a significant reduction in thoracoscopic surgical time.

PMID- 18320279
TI  - Robotic surgery for rectal cancer: may it improve also survival?

PMID- 18320280
TI  - A decision-making learning and assessment tool in laparoscopic cholecystectomy.
AB  - AIMS: Making correct decisions is an integral part of surgical competency and
      excellence. The learning of this expert skill takes years to accumulate during
      training. To date there has not been an attempt to accelerate this learning
      process by developing a tool. In our present study we develop a self-appraisal
      computer software learning and assessment decision-making tool for laparoscopic
      surgery. It aims to accumulate several years of varied surgical experience, so
      the trainee can start to learn the complexities of surgical decision making in
      various types of cases. In this study we aim to validate the tool. METHODS: Three
      decision-making modules were developed in a computer program for laparoscopic
      cholecystectomy: knowledge of operation, operative surgical technique and
      operative task completion. The latter two modules were based on answering
      questions based on watching recorded live operations from a library of 100
      recorded laparoscopic cholecystectomies of various grades. The questions were
      devised by two experienced surgeons with more than 14 years postgraduate surgical
      experience. To validate the tool two groups with varying surgical experience were
      assessed: intermediate and expert surgeons. These groups were determined by the
      number of laparoscopic cholecystectomies performed as well as of number of years
      of operative surgical experience. RESULTS: A total of 20 subjects were assessed,
      12 intermediate and 8 experts surgeons. Mean time to perform the programme was 21
      min (range 18-45 min). Using the Mann-Whitney test, p < 0.05, construct validity
      was demonstrated in the surgical technique and completion of task modules as well
      as the total combined scores. CONCLUSIONS: Our computer-based decision-making
      learning tool for laparoscopic cholecystectomy seems to have face, content,
      concurrent and construct validities. Surgical decision making is a multifaceted
      process; by assessing how and why decisions are made effectively, focussed
      surgical training may be achieved. We aim in the future to determine if the self
      appraisal decision-making tool improves or accelerates surgical training.

PMID- 18320281
TI  - Open versus laparoscopic incisional hernia repair: something different from a
      meta-analysis.
AB  - BACKGROUND: Incisional hernias after laparotomy are a large financial burden for
      society as well as for the patients suffering from pain and limitations of
      activity over time. The introduction of alloplastic materials such as
      polypropylene seems to improve the results. The question of whether to apply open
      or laparoscopic implantation of the mesh is of ongoing interest. We compare the
      available alloplastic materials and try to clarify the question of whether the
      laparoscopic procedure is superior to the conventional (open) technique based on
      the available randomized studies. METHODS: All available meshes for
      intraperitoneal and extraperitoneal implantation were described regarding their
      handling and their pros and cons. A database search (PubMed, Medline, Ovid, and
      in the secondary literature) was carried out to retrieve all randomized studies
      comparing laparoscopic and open hernia repair. Data were reviewed by two
      independent scientists for surgical and statistical design. RESULTS: The ideal
      mesh for a laparoscopic maintenance of abdominal wall hernias as well as the
      optimal fixation of the mesh has not been found yet. Recent available literature
      shows no evidence demonstrating the superiority of one of these meshes. The
      available studies found a lower infection rate, but higher occurrence of seroma
      for the laparoscopic procedure. The value of the different studies is reduced due
      to deficiency in study design and power. Guidelines for further studies are
      discussed to avoid surgical and statistical pitfalls. CONCLUSIONS: Laparoscopic
      incisional hernia repair shows, in some (randomized) studies as well as a large
      number of retrospective analyses and in case control studies, superiority
      compared to conventional hernia repair. Long-term results with a high level of
      evidence are not available. Additional well-designed randomized trials including
      long-term observation of patients are required in order to clarify a number of
      interesting questions.

PMID- 18320282
TI  - Critical evaluation of a novel DualMesh repair for large hiatal hernias.
AB  - BACKGROUND: The use of mesh for laparoscopic repair of large hiatal hernias may
      reduce recurrence rates in comparison to primary suture repair. However, there is
      a potential risk of mesh-related oesophageal complications due to prosthesis
      erosion. The aim of this study was to critically evaluate a novel mesh (DualMesh)
      repair of hiatal hernias with particular reference to intraluminal erosion.
      METHOD: Medical records of 19 patients who underwent laparoscopic hiatal hernia
      repair with DualMesh reinforcement of the crural closure were reviewed from a
      prospectively collected database. Quality of life and symptom analysis was
      performed using quality of life in reflux and dyspepsia (QOLRAD) questionnaires
      pre- and postoperatively after 6 weeks, 6 months, 1 year and 2 years. Barium
      studies were performed on patients pre-operatively and two years postoperatively
      to assess hernia recurrence. After 2 years, oesophagogastric endoscopy was
      performed to assess signs of erosion. RESULTS: Mean patient age was 70.5 years
      (range 49-85 years). Two years after hiatal hernia repair, there was significant
      improvement in quality-of-life scores (QOLRAD: p < 0.001). Follow-up barium
      studies performed at 31.3 months (range 29-40 months) after surgery showed
      moderate recurrent hernias (>4 cm) in 1/14 patients (7%). Endoscopies performed
      at 34.4 months (range 28-41 months) after surgery did not show any signs of
      prosthetic erosion. CONCLUSION: Laparoscopic reinforcement of primary hiatal
      closure with DualMesh leads to a durable repair in patients with large hiatal
      hernias. Long-term endoscopic follow-up did not show any signs of mesh erosion
      after prosthetic reinforcement of the crural repair.

PMID- 18320283
TI  - Laparoscopic ventral rectopexy for obstructed defecation syndrome.
AB  - INTRODUCTION: Obstructed defecation remains a serious syndrome. Several
      procedures have been applied to treat it. A concomitant enterocele excludes some
      of these procedures, because of potential threat of damaging the bowel. The aim
      of this study was to assess the outcome of patients who underwent laparoscopic
      nerve sparing ventral rectopexy for obstructed defecation syndrome with
      concomitant enterocele. METHODS: Seventeen patients were included. Data about
      clinical history, physical examination and a defecogram were collected. All
      patients underwent a laparoscopic ventral rectopexy. Complications, hospital
      stay, postoperative morbidity and long-term outcome were documented. RESULTS: All
      patients underwent laparoscopic ventral rectopexy. The median operating time was
      199 min (range 186-239 min). One conversion laparotomy was required. Six patients
      had postoperative complications (ileus n = 2, posttraumatic leg dystrophy n = 1,
      wound infection n = 1, incisional hernia n = 2). The median hospital stay was 6
      days (range 3-24 days). Fifteen patients had improvement of their defecation
      problem, although six patients still had minor constipation symptoms. In one
      patient the mesh was rejected and finally removed. CONCLUSION: Obstructed
      defecation syndrome is a combined functional and mechanical problem. In selected
      patients, especially when an enterocele is present, laparoscopic ventral
      rectopexy is a feasible technique, with an acceptable number of complications.

PMID- 18320284
TI  - Surgical treatment of hepatocellular carcinoma beyond Milan criteria. Results of
      liver resection, salvage transplantation, and primary liver transplantation.
AB  - BACKGROUND: There is no clear consensus regarding the best treatment strategy for
      patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with
      cirrhosis and HCC beyond Milan who had undergone liver resection (LR) or primary
      orthotopic liver transplantation (OLT) between November 1995 and December 2005
      were included in this study. Pathological tumor staging was based on the American
      Liver Tumor Study Group modified Tumor-Node-Metastasis classification. RESULTS: A
      total of 23 HCC patients were primarily treated by means of LR, 5 of whom
      eventually underwent salvage OLT. An additional 32 patients underwent primary
      OLT. The overall actuarial survival rates at 3 and 5 years were 35% after LR, and
      69% and 60%, respectively, after primary OLT. Recurrence-free survival at 5 years
      was significantly higher after OLT (65%) than after LR (26%). Of the patients who
      underwent LR, 11 (48%) experienced HCC recurrence only in the liver; 6 of these
      11 presented with advanced HCC recurrence, poor medical status, or short disease
      free intervals and were not considered for transplantation. Salvage OLT was
      performed in 5 patients with early stage recurrence (45% of patients with hepatic
      recurrence after LR and 22% of all patients who underwent LR). At a median of 18
      months after salvage OLT, all 5 patients are alive, 4 are free of disease, and 1
      developed HCC recurrence 16 months after salvage OLT. CONCLUSION: For patients
      with HCC beyond Milan criteria, multimodality treatment-including LR, salvage
      OLT, and primary OLT-results in long-term survival in half of the patients. When
      indicated, LR can optimize the use of scarce donor organs by leaving OLT as a
      reserve option for early stage HCC recurrence.

PMID- 18320285
TI  - Survival after pancreatectomy with major arterial resection and reconstruction.
AB  - BACKGROUND: Absence of major arterial tumor involvement has generally been
      regarded as a major criterion for resectability of pancreatic tumors. We
      hypothesize that resection of a tumor-involved hepatic artery (HA) or celiac
      artery (CA) with reconstruction may offer a survival benefit to patients whose
      tumors were traditionally regarded as unresectable. METHODS: All patients with
      pancreatic adenocarcinoma treated between 1996 and 2007 were reviewed. Patients
      were included if they underwent resection of the HA or CA during pancreatectomy.
      Survival was analyzed by Kaplan-Meier survivor functions, Cox proportional hazard
      models, and the log rank test. RESULTS: Twelve patients (six men and six women)
      with adenocarcinoma underwent pancreatectomy with resection of a tumor-involved
      HA (n = 2) and/or CA (n = 10). Median age at diagnosis was 62 years (range, 53-73
      years). All patients completed neoadjuvant chemoradiotherapy with or without full
      dose chemotherapy before resection. Procedures performed were six extended
      pancreaticoduodenectomies, two proximal subtotal pancreatectomies, two distal
      pancreatectomies, and two total pancreatectomies. Ten cases involved celiac
      resections, and two had isolated HA resections. The 60-day mortality was 17% (2
      of 12). Median survival after diagnosis was 20 months (range, 6-41 months).
      Median survival after resection was 17 months (range, 1-36 months). Survival was
      not statistically significantly related to age, sex, margin status, or
      preoperative CA19-9 level. The 3-year survival was 17%. There were no 5-year
      survivors. CONCLUSIONS: Resection of the HA or CA with reconstruction may prolong
      survival for selected patients who undergo pancreatic resection after neoadjuvant
      therapy. However, this aggressive approach did not result in any long-term
      survivors in our series.

PMID- 18320286
TI  - Sorting through the heterogeneity of recurrent melanoma.

PMID- 18320287
TI  - Positive margins: the challenge continues for breast surgeons.

PMID- 18320288
TI  - Intravital microscopic characterization of suramin effects in an orthotopic
      immunocompetent rat model of pancreatic cancer.
AB  - OBJECTIVES: We investigated the effect of suramin on tumor growth and spread in
      an immunocompetent, orthotopic rat model of pancreatic cancer and analyzed the
      tumor vasculature by intravital microscopy. METHODS AND METHODS: In vitro, rat
      ductal pancreatic cancer cells (DSL-6A) were incubated with suramin (10-800
      microg/ml), and cell proliferation was assessed. In vivo, DSL-6A tumors were
      induced in the pancreas of Lewis rats. Animals received suramin (60 mg/kg, weekly
      i.p.) or the vehicle (controls). Treatment started after 3 days. Intravital
      microscopy after 1, 4, and 8 weeks quantified diameter, density, and permeability
      of tumor vessels. Primary tumor volume, local infiltration, and metastatic spread
      were determined at autopsy. Microvessel density was analyzed by
      immunohistochemistry. RESULTS: In vitro, proliferation was inhibited by suramin
      up to 95%. In vivo, all controls developed extensive tumor growth and spread. No
      tumor was detectable in half of the suramin-treated animals after 8 weeks; tumor
      dissemination was almost completely depressed. Suramin therapy resulted in a
      complete regression of tumor macrovessels and a significant reduction of
      microvessel density. CONCLUSION: Suramin significantly reduces primary tumor
      growth and dissemination in a clinically relevant rat model of pancreatic cancer
      and seems to play an important role for the inhibition of tumor angiogenesis.

PMID- 18320289
TI  - Effects of Roux-en-Y gastric bypass on resting energy expenditure in women.
AB  - BACKGROUND: Bariatric surgery is the gold standard treatment for morbid obesity,
      but little is known about its effects on resting energy expenditure. METHOD:
      Twenty-one women underwent anthropometric and resting energy expenditure (REE)
      measurements before and 3 months after bariatric surgery using the Roux-en-Y
      gastric bypass (RYGBP) technique developed by Capella. RESULTS: The patients
      experienced a significant reduction in body weight, body mass index, waist
      circumference, and waist-to-hip ratio (WHR). The cardiopulmonary variables oxygen
      uptake, carbon dioxide output, non-protein respiratory quotient, and heart rate
      all decreased, whereas oxygen pulse did not change significantly. Absolute REE
      showed a significant reduction 3 months postoperatively (2006.7 +/- 376.4
      kcal/day to 1763.3 +/- 310.5 kcal/day), but no significant difference was found
      compared with REE relative to body weight (0.71 +/- 0.15 kcal kg(-1)h(-1) to 0.75
      +/- 0.12 kcal kg(-1) h(-1)) or as percent of Harris-Benedict predicted REE (106.2
      +/- 21.0% to 103.3 +/- 15.1%). CONCLUSION: In this study, bariatric surgery using
      the RYGBP technique (Capella) led to a significant decrease of body weight that
      decreased resting energy expenditure proportional to this weight loss, and to an
      increase in the utilization of fat as an energy substrate. It can be concluded
      that after 3 months, the Roux-en-Y gastric bypass surgery may provide significant
      metabolic benefits to morbidly obese women.

PMID- 18320290
TI  - Gastric carcinoid tumor--incidental finding on endoscopy prior to bariatric
      surgery.
AB  - A 32-year-old female patient with morbid obesity (body mass index 44.4) was
      submitted to upper digestive endoscopy performed routinely as a preoperative
      procedure in bariatric surgery. The examination identified multiple small
      polypoid lesions in the upper portion of the gastric body, some with small
      ulcerations. Anatomo-pathological findings were compatible with carcinoid tumor
      of the stomach. The patient was submitted to extended subtotal gastrectomy with
      loco-regional lymphadenectomy. Upper digestive endoscopy is performed routinely
      in some services for bariatric surgery, but its value has been questioned by some
      authors. In this case, endoscopic examination was of great importance, being
      responsible for a change in the surgical procedure. We did not find any report in
      the literature of a carcinoid tumor of the stomach in morbidly obese patients.

PMID- 18320291
TI  - Prolidase-dependent regulation of collagen biosynthesis.
AB  - Prolidase [EC.3.4.13.9] is a cytosolic imidodipeptidase, which specifically
      splits imidodipeptides with C-terminal proline or hydroxyproline. The enzyme
      plays an important role in the recycling of proline from imidodipeptides (mostly
      derived from degradation products of collagen) for resynthesis of collagen and
      other proline-containing proteins. The enzyme activity is up-regulated by beta(1)
      integrin receptor stimulation. The increase in the enzyme activity is due to its
      phosphorylation on serine/threonine residues. Collagen is not only structural
      component of extracellular matrix. It has been recognized as a ligand for
      integrin receptors, which play an important role in signaling that regulate ion
      transport, lipid metabolism, kinase activation and gene expression. Therefore,
      changes in the quantity, structure and distribution of collagens in tissues may
      affect cell signaling, metabolism and function. Several line of evidence suggests
      that prolidase activity may be a step-limiting factor in the regulation of
      collagen biosynthesis. It has been shown in different physiologic and pathologic
      conditions. It is of great importance during wound healing, inflammation, aging,
      tissue fibrosis and possibly skeletal abnormalities seen in Osteogenesis
      Imperfecta. The mechanism of prolidase-dependent regulation of collagen
      biosynthesis was found at both transcriptional and post-transcriptional levels.
      In this study, we provide evidence for prolidase-dependent transcriptional
      regulation of collagen biosynthesis. The mechanism was found at the level of NF
      kB, known inhibitor of type I collagen gene expression. Modulation of integrin
      dependent signaling by stimulatory (i.e. thrombin) or inhibitory (i.e.
      echistatin) beta(1)-integrin ligands or by nitric oxide donors (i.e. DETA/NO)
      affect prolidase at post-transcriptional level. All those factors may represent
      novel approach to pharmacotherapy of connective tissue disorders.

PMID- 18320292
TI  - Individualization of breast cancer based on histopathological features and
      molecular alterations.
AB  - Histopathological findings and molecular alterations well reflect the biological
      properties of individual primary breast carcinomas. Specifically, pT (size of the
      invasive component), pN (number of metastatic lymph nodes), histological or
      nuclear grade, lymphovascular invasion, hormone receptors, and HER2 (c-erbB-2)
      gene overexpresson or amplification are known to be effective markers for
      assessing the risk of operable primary breast carcinoma, albeit incompletely. It
      is expected that additional molecular markers and novel diagnostic tools will be
      developed in the future to facilitate a more accurate characterization of higher
      risk node-negative breast carcinomas.

PMID- 18320293
TI  - L-NAME inhibits tumor cell progression and pulmonary metastasis of r/m HM-SFME-1
      cells by decreasing NO from tumor cells and TNF-alpha from macrophages.
AB  - Highly metastatic ras/myc-transformed serum-free mouse embryo (r/m HM-SFME-1)
      cells were injected subcutaneously to mice and the effects of Nomega-nitro-L
      arginine methyl ester (L-NAME) on the tumor progression and pulmonary metastasis
      were investigated. In addition, production of nitric oxide (NO), matrix
      metalloproteinases (MMPs) and tumor necrosis factor-alpha (TNF-alpha) in the
      tumor cells and in a mouse macrophage-like cell line, J774.1 cells, was analyzed.
      The increase in footpad thickness was significantly smaller in the mice which
      were fed the L-NAME containing water (4.24+/-0.39 mg/day/mouse). The number of
      the tumor cells metastasized to the lungs was smaller in the L-NAME treated mice,
      although statistical significance was not found. Co-treatment of r/m HM-SFME-1
      cells with interferon-gamma (IFN-gamma; 100 U/ml) and lipopolysaccharide (LPS;
      0.5 microg/ml) significantly enhanced NO production, and the presence of L-NAME
      at 1 mM significantly decreased this response. In r/m HM-SFME-1 cells, MMP-2 was
      undetectable and MMP-9 was also very little in the basal level, and both MMPs
      were unaffected by the IFN-gamma and/or LPS treatments, not to mention by the L
      NAME treatment. In J774.1 cells, any treatment including LPS appeared to enhance
      MMP-9 production, however, this upregulation was not inhibited by the additional
      presence of L-NAME. Production of TNF-alpha by J774.1 cells was markedly enhanced
      with LPS treatment, and this enhancement was significantly reduced in the
      presence of L-NAME. These results indicate that the inhibitory effects of L-NAME
      on the tumor cell progression and pulmonary metastasis could be due to
      suppression of NO from tumor cells and TNF-alpha from macrophages (Mol Cell
      Biochem, 2007).

PMID- 18320294
TI  - Intra and inter-molecular interactions dictate the aggregation state of
      irinotecan co-encapsulated with floxuridine inside liposomes.
AB  - PURPOSE: The inter/intramolecular interactions between drugs (floxuridine,
      irinotecan) and excipients (copper gluconate, triethanolamine) in the dual-drug
      liposomal formulation CPX-1 were elucidated in order to identify the
      physicochemical properties that allow coordinated release of irinotecan and
      floxuridine and maintenance of the two agents at a fixed, synergistic 1:1 molar
      ratio. METHODS: Release of irinotecan and floxuridine from the liposomes was
      assessed using an in vitro-release assay. Fluorescence, Nuclear Magnetic
      Resonance spectroscopy (NMR) and UV-Vis were used to characterize the aggregation
      state of the drugs within the liposomes. RESULTS: Coordinated release of the
      drugs from liposomes was disrupted by removing copper gluconate. Approximately
      45% of the total irinotecan was detectable in the copper-containing CPX-1
      formulation by NMR, which decreased to 19% without copper present in the
      liposomal interior. Formation of higher order, NMR-silent aggregates was
      associated with slower and uncoordinated irinotecan release relative to
      floxuridine and loss of the synergistic drug/drug ratio. Solution spectroscopy
      and calorimetry revealed that while all formulation components were required to
      achieve the highest solubility of irinotecan, direct drug-excipient binding
      interactions were absent. CONCLUSIONS: Long-range interactions between
      irinotecan, floxuridine and excipients modulate the aggregation state of
      irinotecan, allowing for simultaneous release of both drugs from the liposomes.

PMID- 18320295
TI  - What is a suitable dissolution method for drug nanoparticles?
AB  - PURPOSE: Many existing and new drugs fail to be fully utilized because of their
      limited bioavailability due to poor solubility in aqueous media. Given the
      emerging importance of using nanoparticles as a promising way to enhance the
      dissolution rate of these drugs, a method must be developed to adequately reflect
      the rate-change due to size reduction. At present, there is little published work
      examining the suitability of different dissolution apparatus for nanoparticles.
      METHODS: Four commonly-used methods (the paddle, rotating basket and flow-through
      cell from the US Pharmacopia, and a dialysis method) were employed to measure the
      dissolution rates of cefuroxime axetil as a model for nanodrug particles.
      RESULTS: Experimental rate ratios between the nanoparticles and their unprocessed
      form were 6.95, 1.57 and 1.00 for the flow-through, basket and paddle apparatus
      respectively. In comparison, the model-predicted value was 7.97. Dissolution via
      dialysis was rate-limited by the membrane. CONCLUSIONS: The data showed the flow
      through cell to be unequivocally the most robust dissolution method for the
      nanoparticulate system. Furthermore, the dissolution profiles conform closely to
      the classic Noyes-Whitney model, indicating that the increase in dissolution rate
      as particles become smaller results from the increase in surface area and
      solubility of the nanoparticles.

PMID- 18320296
TI  - Significant others and gambling treatment outcomes.
AB  - AIMS: This study investigates the effect of significant others on treatment
      outcomes among treated pathological gamblers. DESIGN: This is a cohort study of
      individuals who received gambling treatment. SETTING: Oregon Problem Gambling
      Services (OPGS) for gamblers and their family members. PARTICIPANTS: 4,410 adult
      gamblers who were discharged from treatment between August, 2001 and April, 2007.
      MEASUREMENTS: OPGS enrollment forms provided gambler gender, age, ethnicity,
      education level, employment status, gambling-related debt, and whether the
      gambler had a significant other at the time of enrollment. Termination forms
      provided information on the type of discharge (successful/unsuccessful) and
      treatment length (in days). Participation of the gambler's significant other in
      the family treatment program was identified. FINDINGS: Results showed that age,
      ethnicity, gambling debt, and having a significant other are associated with the
      odds of successful treatment. Education level moderates the effect of having a
      significant other on treatment success. Age, ethnicity, education, employment,
      and having a significant other participate in treatment significantly impacted
      gamblers' length in treatment. CONCLUSIONS: These findings indicate that there
      may be a benefit to integrating significant others in gambling treatment methods.
      Significant others may act as social supports for gamblers seeking treatment, and
      involving loved ones in gambling treatment models may positively affect gambler
      treatment outcomes.

PMID- 18320298
TI  - Transcatheter ablation of arrhythmias associated with congenital heart disease.
AB  - The improvement of surgical techniques resulted in significant life prolongation
      of many young patients with congenital heart disease (CHD). However, as these
      patients reach adulthood, their risk for late complications associated with
      surgery is also increased. One of the most difficult challenges associated with
      CHD is the high incidence of cardiac arrhythmias that arise from either the
      myocardial substrate created by abnormal physiology (pressure/volume changes,
      septal patches, and suture lines) or the presence of surgical scar. Catheter
      ablation is proven to be effective in treating atrial and ventricular arrhythmias
      in structurally normal hearts, and has also been used to treat arrhythmias in
      adults with congenital heart disease. In this review we provide an overview about
      diagnostic challenges, mapping and ablation techniques and outcome of patients
      undergoing transcatheter ablation procedures.

PMID- 18320299
TI  - Modeling the role of lateral membrane diffusion in AMPA receptor trafficking
      along a spiny dendrite.
AB  - AMPA receptor trafficking in dendritic spines is emerging as a major postsynaptic
      mechanism for the expression of plasticity at glutamatergic synapses. AMPA
      receptors within a spine are in a continuous state of flux, being exchanged with
      local intracellular pools via exo/endocytosis and with the surrounding dendrite
      via lateral membrane diffusion. This suggests that one cannot treat a single
      spine in isolation. Here we present a model of AMPA receptor trafficking between
      multiple dendritic spines distributed along the surface of a dendrite. Receptors
      undergo lateral diffusion within the dendritic membrane, with each spine acting
      as a spatially localized trap where receptors can bind to scaffolding proteins or
      be internalized through endocytosis. Exocytosis of receptors occurs either at the
      soma or at sites local to dendritic spines via constitutive recycling from
      intracellular pools. We derive a reaction-diffusion equation for receptor
      trafficking that takes into account these various processes. Solutions of this
      equation allow us to calculate the distribution of synaptic receptor numbers
      across the population of spines, and hence determine how lateral diffusion
      contributes to the strength of a synapse. A number of specific results follow
      from our modeling and analysis. (1) Lateral membrane diffusion alone is
      insufficient as a mechanism for delivering AMPA receptors from the soma to distal
      dendrites. (2) A source of surface receptors at the soma tends to generate an
      exponential-like distribution of receptors along the dendrite, which has
      implications for synaptic democracy. (3) Diffusion mediates a heterosynaptic
      interaction between spines so that local changes in the constitutive recycling of
      AMPA receptors induce nonlocal changes in synaptic strength. On the other hand,
      structural changes in a spine following long term potentiation or depression have
      a purely local effect on synaptic strength. (4) A global change in the rates of
      AMPA receptor exo/endocytosis is unlikely to be the sole mechanism for
      homeostatic synaptic scaling. (5) The dynamics of AMPA receptor trafficking
      occurs on multiple timescales and varies according to spatial location along the
      dendrite. Understanding such dynamics is important when interpreting data from
      inactivation experiments that are used to infer the rate of relaxation to steady
      state.

PMID- 18320300
TI  - Initiation and propagation of a neuronal intracellular calcium wave.
AB  - The ability to image calcium movement within individual neurons inspires
      questions of functionality including whether calcium entry into the nucleus is
      related to genetic regulation for phenomena such as long term potentiation.
      Calcium waves have been initiated in hippocampal pyramidal cells with
      glutmatergic signals both in the presence and absence of back propagating action
      potentials (BPAPs). The dendritic sites of initiation of these calcium waves
      within about 100 microm of the soma are thought to be localized near oblique
      junctions. Stimulation of synapses on oblique dendrites leads to production of
      inositol 1,4,5-trisphosphate (IP(3)) which diffuses to the apical dendrite
      igniting awaiting IP(3) receptors (IP(3)Rs) and initiating and propagating
      catalytic calcium release from the endoplasmic reticulum. We construct a reduced
      mathematical system which accounts for calcium wave initiation and propagation
      due to elevated IP(3). Inhomogeneity in IP(3) distribution is responsible for
      calcium wave initiation versus subthreshold or spatially uniform suprathreshold
      activation. However, the likelihood that a calcium wave is initiated does not
      necessarily increase with more calcium entering from BPAPs. For low transient
      synaptic stimuli, timing between IP(3) generation and BPAPs is critical for
      calcium wave initiation. We also show that inhomogeneity in IP(3)R density can
      account for calcium wave directionality. Simulating somatic muscarinic receptor
      production of IP(3), we can account for the critical difference between calcium
      wave entry into the soma and failure to do so.

PMID- 18320301
TI  - Evaluation of mediators of change in the treatment of epilepsy with acceptance
      and commitment therapy.
AB  - The present study examined the mediators of change accounting for outcomes of a
      previously published study on acceptance and commitment therapy for the self
      management of epilepsy and its life restricting impact. Conducted with 27 poor
      South Africans, a 9-h ACT protocol that included seizure management methods was
      shown to greatly reduce epileptic seizures and to increase quality of life over
      the next year as compared to an attention placebo control. A series of
      bootstrapped non-parametric multiple mediator tests showed that pre to follow-up
      changes in: seizures, quality of life, and well-being outcomes were mediated to a
      degree by ACT process measures of epilepsy-related acceptance or defusion, values
      attainment, persistence in the face of barriers, or their combination. The
      results of this study contribute to the understanding of the contextual
      conditioning mechanisms at work for those suffering from epilepsy and may show
      that helping people live vital lives may also help to reduce seizures.

PMID- 18320302
TI  - Effects of written anger expression in chronic pain patients: making meaning from
      pain.
AB  - Based on prior research demonstrating benefits of emotional disclosure for
      chronically ill individuals and evidence that anger is particularly problematic
      in chronic pain sufferers, outpatients from a chronic pain center (N=102) were
      randomly assigned to express their anger constructively or to write about their
      goals non-emotionally in a letter-writing format on two occasions. Letters were
      coded for degree of expressed anger and meaning-making (speculation and insight
      into conditions that precipitated anger). Over a 9 week period, participants in
      the anger-expression group (n=51) experienced greater improvement in control over
      pain and depressed mood, and marginally greater improvement in pain severity than
      the control group (n=51). Degree of expressed anger uniquely accounted for
      intervention effects and meaning-making mediated effects on depressed mood. These
      findings suggest that expressing anger may be helpful for chronic pain sufferers,
      particularly if it leads to meaning-making.

PMID- 18320303
TI  - Evaluation of breathing pattern: comparison of a Manual Assessment of Respiratory
      Motion (MARM) and respiratory induction plethysmography.
AB  - Altered breathing pattern is an aspect of dysfunctional breathing but few
      standardised techniques exist to evaluate it. This study investigates a technique
      for evaluating and quantifying breathing pattern, called the Manual Assessment of
      Respiratory Motion (MARM) and compares it to measures performed with Respiratory
      Induction Plethysmography (RIP). About 12 subjects altered their breathing and
      posture while 2 examiners assessed their breathing using the MARM. Simultaneous
      measurements with RIP were taken. Inter-examiner agreement and agreement between
      MARM and RIP were assessed. The ability of the measurement methods to
      differentiate between diverse breathing and postural patterns was compared. High
      levels of agreement between examiners were found with the MARM for measures of
      the upper rib cage relative to lower rib cage/abdomen motion during breathing but
      not for measures of volume. The measures of upper rib cage dominance during
      breathing correlated with similar measures obtained from RIP. Both RIP and MARM
      measures methods were able to differentiate between abdominal and thoracic
      breathing patterns, but only MARM was able to differentiate between breathing
      changes occurring as result of slumped versus erect sitting posture. This study
      suggests that the MARM is a reliable clinical tool for assessing breathing
      pattern.

PMID- 18320304
TI  - Sex hormone concentrations and gonad histology in brown trout (Salmo trutta)
      exposed to 17beta-estradiol and bisphenol A.
AB  - The impact of 17beta-estradiol (E2) and bisphenol A (BPA) on steroid hormone
      levels and gonad development in brown trout (Salmo trutta) was determined.
      Exposure took place from 0 to 63 days post-fertilisation (dpf) and gonad
      development was followed till 400 dpf. The onset of xenoestrogen metabolism was
      examined by measurements of whole body concentrations of bisphenol A (BPA) and
      its conjugation product bisphenol A glucuronic acid (BPAGA). Exposure to 500 ng
      E2/l led to an increase in E2 levels in the embryos and fry while 10 ng E2/l did
      not. Metabolic conversion of BPA to BPAGA began during the first weeks of
      embryonic development. Few consistent effects were found on the sex
      differentiation of the brown trout. Only one intersex fish (4.5%) was found among
      male fish at 400 dpf exposed to 500 ng E2/l. Females with male germ cells among
      the normally developing oocytes were observed in all groups (in up to 50% of the
      female fish, independently of exposure regime). The fact that exposure to 500 ng
      E2/l only caused subtle effects in a small number of individuals indicates that
      exposure during early life stages results in little to no induction of endocrine
      disruption in brown trout.

PMID- 18320305
TI  - Protein levels and activity of some antioxidant enzymes in hippocampus of
      subjects with amnestic mild cognitive impairment.
AB  - Mild cognitive impairment (MCI) is generally referred to the transitional zone
      between normal cognitive aging and early dementia or clinically probable
      Alzheimer's disease (AD). Most individuals with amnestic MCI eventually develop
      AD, which suggests that MCI may be the earliest phase of AD. Oxidative stress is
      observed in brain from subjects with both AD and MCI. Among others, two
      possibilities for elevated oxidative stress are decreased activity or elevated
      expression of antioxidant enzymes, the latter as a response to the former.
      Accordingly, in the current study, the protein levels and activity of some
      antioxidant enzymes in the hippocampus of control and MCI brain were measured
      using Western blot analysis and spectrophotometric methods, respectively.
      Alterations in the levels and activity of a number of antioxidant enzymes in MCI
      brain compared to age-matched controls were found. These results are consistent
      with the hypothesis that oxidative stress may be an early event in the
      progression of amnestic MCI to AD.

PMID- 18320306
TI  - Role of tuberin in neuronal degeneration.
AB  - One of the tuberous sclerosis complex (TSC) gene products, tuberin is assumed to
      be the functional component, being involved in a wide variety of cellular
      processes. Here, we report for the first time that tuberin dysfunction may
      represent a mechanism for neuronal damage in Alzheimer's disease (AD),
      Parkinson's disease with dementia (PD/DLB), and a mouse model of PD. Tuberin was
      hyperphosphorylated at Thr1462 in post-mortem frontal cortex tissue of both AD
      and PD/DLB patients and in mice treated with 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine hydrochloride (MPTP). Both PTEN and Akt phosphoactivation
      corresponded to the hyperphosphorylation patterns of tuberin suggesting that the
      PTEN-Akt pathway might be the mechanism of tuberin phosphorylation. Our data
      provide new information regarding the possible role of tuberin dysfunction in
      major neurodegenerative disorders, such as AD and PD, whereby inhibition of
      tuberin function may trigger an onset of neuronal cell death.

PMID- 18320307
TI  - Biliary complications associated with selective internal radiation (SIR) therapy
      for unresectable liver malignancies.
AB  - Selective internal radiation (SIR) therapy using 90yttrium microspheres is
      effective for treating selected cases of unresectable liver malignancies with
      little morbidity. We herein report two cases illustrating a very rare
      complication of SIR. A 68-year-old patient with inoperable recurrent
      hepatocellular carcinoma received one treatment of SIR with 90yttrium
      microspheres and 4 months later presented with obstructive jaundice. Percutaneous
      transhepatic cholangiography revealed diffusely dilated intrahepatic ducts with
      multiple biliary strictures. Hepatic angiography showed normal hepatic arterial
      branches with no evidence of vascular insufficiency. Liver biopsy finally
      revealed cholestasis, cholangitis, and fibrosis, consistent with radiation
      induced damage. Another 56-year-old patient with unresectable colorectal liver
      metastases presented with cholangitis 4 weeks after SIR. Ultrasonography showed
      no biliary dilatation, and endoscopic retrograde cholangiopancreatography
      demonstrated a normal biliary tree. Liver biopsy subsequently confirmed radiation
      induced cholangitis.

PMID- 18320308
TI  - Altered expression of the PMAIP1 gene: A major player in the evolution of
      gastrointestinal and systemic malignancies.

PMID- 18320309
TI  - Clonidine therapy for pancreatitis.

PMID- 18320310
TI  - Acute appendicitis associated with Peutz-Jeghers-type hamartoma of the appendix.

PMID- 18320311
TI  - c-Jun, Fra-2, and ATF-2 immunoreactivity in the jejunal tissues of the healthy
      rat.
AB  - The aim of this study was to compare the localization of some activator protein-1
      (AP-1) proteins in healthy rat jejunum. For this purpose, the AP-1 members c-Jun,
      Fra-2, and ATF-2 immunoreactivity (c-Jun-IR, Fra-2-IR, ATF-2-IR) in villus
      epithelial cells (ECs), intravillous lamina propria cells (LPCs), crypt cells
      (CCs), and smooth muscle cells (SMCs) were analyzed by immunohistochemical
      methods. Among all the cell groups, the lowest positivity ratio was found in c
      Jun-IR and the highest positivity ratio was found in ATF-2-IR. For each group of
      ECs, LPCs, CCs, and SMCs, c-Jun-IR, Fra-2-IR, and ATF-2-IR were compared and
      statistically significant differences found. There were no significant
      differences among the cell groups with respect to c-Jun-IR and Fra-2-IR, but
      there was a statistically significant difference in ATF-2-IR. These findings
      suggest that each member of AP-1 is expressed differently and that ATF-2 is more
      active than c-Jun and Fra-2 in physiological conditions in healthy rat jejunum.

PMID- 18320312
TI  - Alanyl-glutamine and glutamine supplementation improves 5-fluorouracil-induced
      intestinal epithelium damage in vitro.
AB  - In this study, we have examined the role of glutamine derivatives in reducing 5
      fluorouracil (5-FU)-induced epithelial damage in an undifferentiated crypt
      intestinal cell line, IEC-6. In this model, we have investigated proliferation
      indirectly by detecting the enzyme-derived formazan dye from the tetrazolium salt
      WST-1 in viable cells at 24 and 48 h after 5-FU treatment. Migration was measured
      at 12 and 24 h after razor scraping of the cell monolayer. Cell death was
      measured by quantifying the percentage of apoptotic and necrotic figures by flow
      cytometry at 12 and 24 h following 5-FU challenge. Neither glutamine nor alanyl
      glutamine prevented 5-FU-induced apoptosis and necrosis in IEC-6 cells at 12 and
      24 h after 5-FU challenge. However, glutamine and alanyl-glutamine enhanced
      migration and proliferation when compared with 5-FU-treated controls (P < 0.05).
      These new findings support our earlier study on the benefit of oral glutamine in
      enhancing epithelial recovery after 5-FU challenge.

PMID- 18320313
TI  - Safety, reliability and limitations of the given patency capsule in patients at
      risk of capsule retention: a 3-year technical review.
AB  - INTRODUCTION: The patency capsule may prevent capsule retention in high-risk
      patients. However data on its use in routine clinical practice is limited.
      METHODS: Patients referred to our institution between Feb-04 and Jan-07 were
      reviewed. The following data was collected: presenting symptoms; medical/surgical
      history; medication; radiology; patency/video capsule result; subsequent
      investigations; clinical outcomes. RESULTS: 373 patients were referred. In 315
      (84%) 'low-risk' patients (no patency capsule): delayed transit occurred in
      three, with no cases of capsule retention. In 58 (16%) 'high risk' patients
      (patency capsule): asymptomatic retention occurred in eight, all with pathology
      despite normal prior barium studies in six; in four cases patency location was
      incorrectly assessed radiologically, leading to video capsule retention and
      surgery in one. DISCUSSION: Most patients can safely undergo capsule endoscopy
      without a patency capsule. The patency capsule appears safe and is indicative of
      pathology when retained. Assessment of patency capsule location post ingestion
      can be difficult, and if barium radiology is equivocal a limited abdominal
      computed tomography (CT) scan is suggested.

PMID- 18320314
TI  - Hepatic sarcoidosis associated with pegylated interferon alfa therapy for chronic
      hepatitis C: case report and review of literature.

PMID- 18320315
TI  - Antral inflammatory cells, gastric emptying, and electrogastrography in pediatric
      functional dyspepsia.
AB  - The aims of the current study were to determine the activation states of antral
      eosinophils and mast cells and to evaluate the interactions of antral
      inflammatory cells with gastric emptying and electrogastrography (EGG) in 30
      pediatric patients with functional dyspepsia. Eosinophil degranulation was
      moderate in 42% and extensive in 54% of patients. Mast cell degranulation was >
      50% in 81% of patients. Elevated mast cell density was associated with slower one
      hour gastric emptying and increased preprandial dysrhythmia. Mast cell density
      correlated with the preprandial percentage tachygastria. CD3+ cell density
      correlated with the preprandial percentage tachygastria also, but only in
      patients with increased eosinophil density. In conclusion, antral eosinophils and
      mast cells are significantly activated in pediatric functional dyspepsia. Mast
      cell density is associated with delayed gastric emptying and preprandial
      dysrhythmia, suggesting that there may be an interaction between antral
      inflammation and gastric electromechanical dysfunction in the pathophysiology of
      pediatric functional dyspepsia.

PMID- 18320316
TI  - Endoscopic ultrasonography findings in patients with non-specific changes of the
      pancreas on computed tomography: a single-center experience.
AB  - Inconclusive findings on abdominal computerized tomography (CT) scans such as
      "enlarged or prominent pancreas" are commonly reported; however, their clinical
      significance is not clearly understood. The objective was to evaluate the
      efficacy of endoscopic ultrasound (EUS) in a cohort of patients with
      indeterminate findings on CT. We undertook a retrospective, single-center study
      at a tertiary care university hospital. About 107 consecutive patients (56 men)
      underwent EUS evaluation for inconclusive CT findings. The main intervention was
      EUS with fine needle aspiration (FNA) The main outcome measurement was to
      describe lesions identified by EUS in this cohort of patients. About 22 patients
      (21%) had pancreatic adenocarcinoma, 14 (13%) had chronic pancreatitis, 28 (26%)
      had benign lesions, and 35 patients (33%) had a normal EUS exam. Pancreatic
      cancer was more likely to be found on EUS in patients with significant weight
      loss (OR 10.1; 95% CI: 3.3-30.60), hyperbilirubinemia (OR 9; 95% CI: 3-26.0), or
      common bile duct (CBD) dilatation (OR 3.2; 95% CI: 1.25-8.5). The limitations of
      the study were that we were unable to control the uniformity of CT interpretation
      because the scans were reviewed by multiple radiologists. There were also limited
      follow-up data on patients who had benign lesions or normal EUS. In conclusion,
      EUS is an effective modality for evaluating pancreatic lesions in patients with
      inconclusive findings on abdominal CT. This assists in the prompt diagnosis and
      institution of appropriate treatment strategies for a variety of pancreatic
      diseases including cancer. In the setting of inconclusive CT findings, patients
      with hyperbilirubinemia, significant weight loss, or CBD dilatation should
      undergo EUS evaluation as they are at a higher risk of having underlying
      pancreatic cancer.

PMID- 18320317
TI  - Endoscopic visualization of angiotensin-converting enzyme inhibitor-induced small
      bowel angioedema as a cause of relapsing abdominal pain using double-balloon
      enteroscopy.
AB  - A 40-year-old woman presented with 3 episodes of abdominal pain. Abdominal
      ultrasound demonstrated edema of the small bowel. Double-balloon enteroscopy
      (DBE) showed diffuse swelling of the small intestine, petechial bleeding in the
      jejunum, and focal inflammation of the ileum. Pain and small bowel edema resolved
      spontaneously within 48 h during each episode. Review of the patient's history
      revealed that she had been started on enalapril for arterial hypertension two
      weeks before her first episode. Angiotensin-converting enzyme (ACE) inhibitor
      associated angioedema of the small bowel was suspected and enalapril was
      discontinued. The patient remained symptom-free after discontinuing the ACE
      inhibitor. Review of the literature reveals only 11 similar cases with this case
      being the first to apply DBE to visualize macroscopic alterations to the small
      intestine. Angioedema of the intestine is a diagnostic pitfall frequently leading
      to prolonged diagnostic procedures and is a potential cause for abdominal pain in
      patients taking ACE inhibitors.

PMID- 18320318
TI  - An assessment of the accuracy of hepatic and splenic size based upon a
      clinician's physical examination, a radiologist's impression and the actual liver
      and spleen volumes calculated by CT scanning.
AB  - OBJECTIVES: In this study, a radiologist's impression of liver and spleen size
      based on computed tomography (CT) images, calculated liver and spleen volumes as
      determined radiologically, and findings of a hepatologist were compared. METHODS:
      One hundred and ninety-four consecutive subjects seen by a hepatologist were
      evaluated clinically and radiologically. Liver and spleen volumes were calculated
      based on CT images and compared to radiologist's impression and to expected liver
      volume based on body weight. Covariate analysis was used to determine the
      relationships between different variables, and a value of P < 0.05 was considered
      to be significant. RESULTS: Liver volume calculated on the basis of CT scans
      correlated to liver size based on the hepatologist's clinical exam but not to the
      radiologist's impression of liver size. In contrast, spleen volume based on CT
      scans, splenic size based upon radiologist's impression, and clinician's
      assessment all correlated well. CONCLUSIONS: A variety of biases determine and/or
      affect the radiologist's assessment of liver size but not of splenic size.

PMID- 18320319
TI  - Helicobacter pylori prevalence in diabetes mellitus patients with dyspeptic
      symptoms and its relationship to glycemic control and late complications.
AB  - BACKGROUND: There are contradictory reports on Helicobacter pylori prevalence and
      its relationship to late complications of diabetes mellitus (DM). The aim of this
      study was to determine the prevalence of H. pylori infection in type 2 DM
      patients and to evaluate the relationship between H. pylori infection and the
      glycemic control, late complications. MATERIAL AND METHOD: A total of 141 type 2
      DM patients and 142 nondiabetic subjects with upper gastrointestinal symptoms
      were enrolled in the study. All patients underwent upper gastrointestinal
      endoscopy with biopsy specimens obtained from gastric antrum and corpus. H.
      pylori status was evaluated in each patient by both the rapid urease test and
      histopathological examination. Plasma glucose, HbA1c, microalbuminuria in 24 h
      collected urine, electroneuromyography, and fundoscopic examinations were
      performed in all subjects. RESULTS: The prevalence of H. pylori infection was
      61.7% and 58.5%, respectively, among type 2 diabetic patients and nondiabetic
      controls and was not statistically significant (P = 0.577). The duration of
      diabetes, fasting blood glucose and haemoglobin A1c levels, nephropathy and
      retinopathy prevalence did not differ significantly between the two groups
      (diabetics versus nondiabetics). There was no late complication in 60.3% of the
      type 2 diabetic patients as compared to at least one late complication in the
      remainders. A statistically significant correlation was found between H. pylori
      infection and the presence of neuropathy (P = 0.021). CONCLUSIONS: The prevalence
      of H. pylori infection did not differ significantly between the diabetic patients
      and nondiabetic controls. Interestingly, diabetics with H. pylori infection had a
      higher incidence of neuropathy, although there was no association between the
      duration and regulation of diabetes, retinopathy, nephropathy and H. pylori
      status.

PMID- 18320320
TI  - Lactulose/mannitol test and specificity, sensitivity, and area under curve of
      intestinal permeability parameters in patients with liver cirrhosis and Crohn's
      disease.
AB  - The purpose of this study was to investigate and compare the specificity,
      sensitivity, and area under curve (AUC) of the lactulose/mannitol ratio,
      lactulose/creatinine ratio, and lactulose recovery and their diagnostic value for
      intestinal permeability assessment within the absorption lactulose/mannitol (L/M)
      test. RESULTS: The value of the lactulose/mannitol ratio, lactulose/creatinine
      ratio, and the percentage of lactulose recovery in Crohn's disease (0.0763 +/-
      0.0369; 99.62 +/- 67.87; 1.0478 +/- 0.6148) and in liver cirrhosis (0.0517 +/-
      0.0365; 54.65 +/- 53.26; 0.838 +/- 0.929) were significantly different from the
      values measured in the control group (0.0123 +/- 0.0081; 10.95 +/- 7.07; 0.2438
      +/- 0.1568), P < 0.0001-0.002). In Crohn's disease, specificity, sensitivity, and
      AUC were 100%, 89.5%, and 0.987, respectively, of the lactulose/mannitol ratio at
      a cut-off level of 0.022. In liver cirrhosis, the test characteristics were
      88.5%, 84.2%, and 0.910 at a cut-off level of 0.018. CONCLUSION: The
      lactulose/mannitol ratio was evaluated to have the highest diagnostic value to
      assess intestinal permeability.

PMID- 18320321
TI  - Bioflora probiotic in immunomodulation and prophylaxis of intestinal bacterial
      translocation in rats.
AB  - The immunomodulator effect of Bioflora probiotic on T (CD4+) and B (CD20)
      lymphocytes in gastrointestinal mucosa and intestinal bacterial translocation was
      studied using Wistar rats (n = 10 per group). Two experiments were used: (I)
      stress with immobilization and water immersion at 22 degrees C for 7 h plus the
      application of indomethacin (Indo) 10 mg/kg SC every 24 h for 3 days (comparator
      group), and (II) stress experiment I with the addition of 1 mL of Bioflora
      applied through a orogastric tube every 12 h for 3 days. At the 4th day, in
      asepsis, a dissection laparotomy of liver, spleen, mesenteric lymphatic nodes,
      and cecum was performed for microbiological culture, and stomach, ileum, and
      colon were also dissected for immunohistochemical and quantification of CD4+ and
      CD20. Findings in experiment I revealed cecum bacterial overdevelopment of 6 x
      10(10) +/- 2.3 x 10(9) colony-forming units (CFU) (P < 0.01) and positive
      cultures in liver, spleen, and all mesenteric lymphatic nodes. On the other hand,
      in the group treated with Probiotic Bioflora, cecum without overdevelopment (3 x
      10(6) +/- 1.3 x 10(5) CFU), negative cultures in liver and spleen, and in
      lymphatic nodes two positive and eight negative cultures for E. coli and P.
      vulgaris (P < 0.01) were observed. Immunohistochemistry revealed a relevant
      increase of T lymphocytes (CD4+) in ileum and colon. CONCLUSIONS: Bioflora
      probiotic was shown to be an intestinal immunomodulator that induced increased T
      (CD4+) lymphocytes that also offer prophylaxis of intestinal bacterial
      translocation in a stressed rat model.

PMID- 18320322
TI  - Laryngopharyngeal reflux disease treated with laparoscopic fundoplication.
AB  - The objective of this clinical prospective study was to find out if laparoscopic
      Nissen fundoplication is an effective treatment in laryngopharyngeal reflux
      disease. Twenty-two consecutive patients, 16 female and 6 male, who were referred
      to laparoscopic fundoplication and operated by a senior gastroenterology surgeon
      were included in this study. Their mean age was 41 years (SD 13), and ranged from
      18 to 64. The patients selected for surgical treatment had LPRD with several
      vocal and laryngeal symptoms. The status findings were typical for
      laryngopharyngeal reflux and the symptoms and signs had responded to antireflux
      medication. Vocal symptoms were interviewed and patients underwent laryngoscopy,
      esophagogastroscopy, and 24-h esophageal pH monitoring. The follow-up of symptoms
      and signs were 3 months after beginning of medication, before surgery, 3 months,
      and 1 year after surgery. The number of patients experiencing vocal symptoms
      decreased during the medical treatment, from the situation before medical
      treatment to the situation before surgery (P < 0.001), from the situation before
      surgery to the situation 3 months (P < 0.001) and 1 year post operation (P <
      0.001), but no significant changes were found from the situation 3 months to 1
      year post operation. Voice quality improved significantly only from the time
      point before surgery to 3 months post operation. Three months after medical
      treatment, laryngeal and pharyngeal findings did not decrease significantly, but
      several findings decreased significantly (P < 0.001) from the time point before
      surgery compared to 3 months and to 1 year post operation. Based on this study,
      the laparoscopic fundoplication is an effective and safe treatment of LPRD.

PMID- 18320323
TI  - Adherence, internalization, and persistence of Helicobacter pylori in
      hepatocytes.
AB  - Although Helicobacter pylori have been identified in the liver, the role of
      Helicobacter sp. in human liver diseases remains unclear. This study explored
      whether H. pylori were internalized and could persist in hepatocytes. The
      majority of an inoculum of H. pylori (1 x 10(7) colony forming units) adhered to
      hepatocytes. Using the gentamicin invasion assay we found that approximately 2%
      were internalized and persisted following passage for more than 2 months.
      Electron microscopy confirmed the presence of intracellular Helicobacter. The
      number of adherent or internalized H. pylori was significantly greater with
      hepatocytes than with gastric epithelial cells (P < 0.05) and was also dependent
      on cag pathogenicity island (PAI), VacA, OipA, or BabA status. Transmission
      electron microscopy was used to confirm adherence and invasion of H. pylori into
      hepatocytes. Internalization of H. pylori was inhibited by antibodies to beta1
      integrin receptors, genistein, and cytochalasin D (P < 0.05) consistent with
      beta1-integrin acting as a surface receptor with additional requirements for
      tyrosine kinase phosphorylation and actin polymerization. In summary, H. pylori
      both adhered to and invaded into hepatocytes in vitro, depending on the virulent
      factors, and persisted within hepatocytes during subcultures. beta1-integrin is
      likely a receptor involved in internalization of H. pylori into hepatocytes.

PMID- 18320324
TI  - Serrated adenoma is a risk factor for subsequent adenomatous polyps.
AB  - BACKGROUND: Serrated adenomas (SA) are histologically defined by the presence of
      both hyperplastic and adenomatous features. These uncommon polyps are thought to
      play an important role in the development of sporadic colorectal cancers (CRC)
      with microsatellite instability (MSI). There is paucity of data on the risk of
      progression of SA to CRC. This study was undertaken to define the relationship
      between SA and the future development of adenomatous polyps. METHODS:
      Colonoscopic biopsies that contained a pathologic diagnosis of SA were identified
      from a pathology database of a major urban academic medical center. Those
      patients with absence of concomitant malignancy, complete colonoscopy, good or
      adequate prep and presence of at least one follow-up procedures were identified.
      These were matched to controls by age, sex, indication for colonoscopy, polyp
      type and number and duration of follow-up. Outcomes of the follow-up procedures
      were compared. RESULTS: Between January 1997 and June 2005 17,226 colonoscopic
      biopsies and polypectomies were performed. Of these, 80 patients (0.5%) with SA
      were found, and of these SA, 80% were found in the left colon. The average age of
      patients undergoing colonoscopy was 58.5 years, and the average age of patients
      with SA was 68 years (P = 0.004). Of all patients with SA, 7 (9%) had concomitant
      CRC. The final groups contained 17 patients and 17 controls, respectively, and
      were well matched. The mean follow-up interval in the patient group was 29 months
      vs. 31 months in the control group (P = 0.82). On follow-up examination four
      patients (24%) and no controls had adenomatous polyps (P = 0.01). CONCLUSIONS:
      While SA are uncommon, they are commonly associated with colorectal cancer.
      Serrated adenomas appear to be found more commonly in the left colon and in older
      patients. This study found a significant association between SA and the
      subsequent development of adenomatous polyps. Further studies are needed to
      define appropriate preventive strategies for these patients.

PMID- 18320325
TI  - The COX-2 selective inhibitor-independent COX-2 effect on colon carcinoma cells
      is associated with the Delta1/Notch1 pathway.
AB  - BACKGROUND: Cyclooxygenase-2 (COX-2) is a key factor in the development of
      colorectal cancer, and non-steroidal anti-inflammatory drugs (NSAIDs) have anti
      colorectal cancer activity. However, the potential molecular mechanism of the COX
      2 selective inhibitor effect on proliferation and apoptosis of colon cancer cells
      is unclear. In this study, we have demonstrated for the first time that the
      Delta1/Notch1 signal transduction pathway mediates the COX-2 selective inhibitor
      effect on colorectal cancer cells, and we reveal the mechanism of the Notch1
      pathway in terms of regulating the proliferation and apoptosis of colorectal
      cancer cells. METHODS AND RESULT: Colon cancer cell lines HT-29 and SW480 were
      treated with NS-398 (a COX-2 selective inhibitor) and DAPT (a gamma-secretase
      inhibitor). The colormetric MTT cell proliferation assay and flow cytometry were
      used to measure cell proliferation and apoptosis. Reverse transcriptase (RT)-PCR
      and ELISA analyses were used to detect the levels of COX-2 mRNA expression and
      prostaglandin E2 (PGE2) concentration from the two cell lines, respectively. The
      expression of the Notch1, Delta1, ICN, Hes1 and NF-kappaB2 proteins was measured
      by Western blot. Immunohistochemistry results showed that Notch1 was expressed
      mainly in the cytoplasm and ICN mainly in the nucleus. COX-2 mRNA was highly
      expressed in HT-29 cells but not in SW480 cells. Both COX-2 mRNA expression and
      PGE2 concentration decreased in HT-29 cells treated with NS-398; however, PGE2
      levels did not change in SW480 cells treated with NS-398. NS-398 and DAPT
      inhibited cell proliferation and induced apoptosis in a dose time-dependent
      manner accompanied by significantly decreased Notch1 activity (P < 0.01), and
      resulted in a significant down-regulation of Hes1 and NF-kappaB2 (P < 0.01).
      CONCLUSIONS: Our results show that the selective COX-2 inhibitor may inhibit the
      proliferation and induce apoptosis in colon cancer cells through the COX-2
      dependent pathway (HT-29) by decreasing the COX-2 mRNA/PGE2 levels and the
      activity of the COX-2-independent pathway (SW480). The Notch1 signal pathway
      mediates the effects of the COX-2 inhibitor on the proliferation and apoptosis of
      colon cancer cells. This may be a new target of the selective COX-2 inhibitor
      effect on colon cancer.

PMID- 18320326
TI  - A rare case of paraganglioma of the sella with bone metastases.
AB  - Sellar paragangliomas are very rare lesions with only 11 previous cases described
      in the literature. We present a further case of sellar paraganglioma. The patient
      is a 17-year-old man who developed headache, visual blurring, and diplopia. MRI
      showed a sellar lesion. Trans-nasal trans-sphenoid biopsy showed features of
      paraganglioma. He was treated by Stereotactic radiotherapy. Four months after
      treatment he developed bone metastases which was palliated by radiation,
      zoledronic acid, and chemotherapy. This is the first case of sellar paraganglioma
      showing metastases to bone.

PMID- 18320327
TI  - Postoperative assessment of the patient after transsphenoidal pituitary surgery.
AB  - While most transsphenoidal pituitary surgery is accomplished without
      complication, monitoring is required postoperatively for a set of disorders that
      are specific to this surgery. Postoperative assessments are tailored to the early
      and later postoperative periods. In the early period, which spans the first few
      weeks after surgery, both monitoring of anterior and posterior pituitary function
      and managing neurosurgical issues are the focus of care. Potential disruption of
      pituitary-adrenal function is covered with perioperative glucocorticoids. Various
      strategies exist for ensuring the integrity of this axis, but typically this is
      done by measuring a morning cortisol on the 2nd or 3rd postoperative days.
      Patients with levels <10 microg/l should continue therapy with reassessment in
      the later postoperative period. Monitoring for water imbalances, which are due to
      deficiency or excess of ADH (DI or SIADH, respectively), is accomplished by
      continuous accounting of fluid intake, urine output and specific gravities
      coupled with daily serum electrolyte measurements. DI is characterized by excess
      volumes of inappropriately dilute urine, which can lead to hypernatremia. Most
      patients maintain adequate fluid intake and euvolemia, but desmopressin therapy
      is required for some. SIADH, which peaks in incidence on 7th postoperative day,
      presents with hyponatremia that can be severe and symptomatic. Management
      consists of fluid restriction. Neurosurgical monitoring is primarily for
      disturbances in vision or neurological function, and although uncommon, for CSF
      leak and infections such as meningitis. In the later postoperative period, the
      adrenal, thyroid and gonadal axes are assessed. New persistent hypopituitarism is
      rare when transsphenoidal surgery is performed by an experienced surgeon. Various
      strategies are available for assessing each axis and for providing replacement
      therapy in patients with deficiencies. Long term monitoring with assessments of
      visual, neurological and pituitary function coupled with pituitary imaging is
      necessary for all patients who have undergone surgery, irrespective of the
      hormone status of their tumors.

PMID- 18320328
TI  - Murine Itk SH3 domain.

PMID- 18320329
TI  - Structural constraints for the Crh protein from solid-state NMR experiments.
AB  - We demonstrate that short, medium and long-range constraints can be extracted
      from proton mediated, rare-spin detected correlation solid-state NMR experiments
      for the microcrystalline 10.4 x 2 kDa dimeric model protein Crh. Magnetization
      build-up curves from cross signals in NHHC and CHHC spectra deliver detailed
      information on side chain conformers and secondary structure for interactions
      between spin pairs. A large number of medium and long-range correlations can be
      observed in the spectra, and an analysis of the resolved signals reveals that the
      constraints cover the entire sequence, also including inter-monomer contacts
      between the two molecules forming the domain-swapped Crh dimer. Dynamic behavior
      is shown to have an impact on cross signals intensities, as indicated for mobile
      residues or regions by contacts predicted from the crystal structure, but absent
      in the spectra. Our work validates strategies involving proton distance
      measurements for large and complex proteins as the Crh dimer, and confirms the
      magnetization transfer properties previously described for small molecules in
      solid protein samples.

PMID- 18320330
TI  - The war of tools: how can NMR spectroscopists detect errors in their structures?
AB  - Protein structure determination by NMR methods has started in the mid-eighties
      and has been growing steadily since then. Ca. 14% of the protein structures
      deposited in the PDB have been solved by NMR. The evaluation of the quality of
      NMR structures however is still lacking a well-established practice. In this
      work, we examined various tools for the assessment of structural quality to
      ascertain the extent to which these tools could be applied to detect flaws in NMR
      structures. In particular, we investigated the variation in the scores assigned
      by these programs as a function of the deviation of the structures induced by
      errors in assignments or in the upper distance limits used. These perturbations
      did not distort radically the protein fold, but resulted in backbone RMS
      deviations up to 3 A, which is in line with errors highlighted in the available
      literature. We found that it is quite difficult to discriminate the structures
      perturbed because of misassignments from the original ones, also because the
      spread in score over the conformers of the original bundle is relatively large.
      varphi-psi distributions and normality scores related to the backbone
      conformation and to the distribution of side-chain dihedral angles are the most
      sensitive indicators of flaws.

PMID- 18320331
TI  - Population cytogenetics of Chironomus circumdatus Kieffer, 1921 (Diptera,
      Chironomidae) from Thailand.
AB  - The objectives of this study were to explore cytogenetic variation and the role
      of chromosomal change on local adaptation and genetic differentiation of
      Chironomus circumdatus Kieffer from Thailand. A total of 1,505 larvae from 24
      populations were examined cytologically. Twelve chromosomal inversions were found
      and most of these (9 of 12) were rare inversions. All populations were in Hardy
      Weinberg equilibrium. Significant association (P < 0.001) between the A2 and B5
      inversions was detected in one population. Population genetic structure analysis
      indicated significant genetic differentiation between populations (F (ST) =
      0.037, P < 0.001). Geographic distance was the principal factor limiting gene
      flow between populations. Nei's modified genetic distance (D (A)) between
      populations ranged from 0.001 to 0.011 with an average of 0.003. An UPGMA
      population phenogram depicting relationship between populations based on D (A)
      values revealed three groups of populations, group I, II and III each
      characterized by different inversions/inversion frequencies. Significant
      correlation of inversion C3 and water temperature suggested that this inversion
      might have a role to play on adaptation to high temperature habitat. However, if
      detection of significant population subdivision and relationship between genetic
      and geographic distance are taken into account, relationship between C3 and water
      temperature will also be due to the effect of migration/drift alone without the
      effect of selection.

PMID- 18320332
TI  - Natural radioactivity and trace metals in crude oils: implication for health.
AB  - Crude oil samples were collected from six different fields in the central Niger
      Delta in order to determine their natural radioactivity and trace element
      contents, with the aim of assessing the radiological health implications and
      environmental health hazard of the metals, and also to provide natural
      radioactivity baseline data that could be used for more comprehensive future
      study in this respect. The activity concentrations of the radionuclides were
      measured using a well, accurately calibrated and shielded vertical cryostat,
      Canberra coaxial high-purity germanium (HPGe) detector system, and the derived
      doses were evaluated. The metal concentrations were determined by the graphite
      furnace atomic absorption spectroscopic (GFAAS) method. The radionuclides
      identified with reliable regularity belong to the decay series of naturally
      occurring radionuclides headed by (238)U and (232)Th along with the non-decay
      series radionuclide, (40)K. The averaged activity concentrations obtained were
      10.52 +/- 0.03 Bq kg(-1), 0.80 +/- 0.37 Bq kg(-1) and 0.17 +/- 0.09 Bq kg(-1) for
      (40)K, (238)U and (232)Th, respectively. The equivalent doses were very low,
      ranging from 0.0028 to 0.012 mSv year(-1) with a mean value of 0.0070 mSv year(
      1). The results obtained were low, and hence, the radioactivity content from the
      crude oils in the Niger delta oil province of Nigeria do not constitute any
      health hazard to occupationally exposed workers, the public and the end user. The
      concentrations of the elements (As, Cd, Co, Fe, Mn, Ni, Se and V) determined
      ranged from 0.73 to 202.90 ppb with an average of 74.35 ppb for the oil samples
      analysed. The pattern of occurrence of each element agreed with the earlier
      studies from other parts of the Niger Delta. It was obvious from this study and
      previous ones that the Niger Delta oils have low metal contents. However, despite
      the low concentrations, they could still pose an intrinsic health hazard
      considering their cumulative effects in the environment. Also, various studies on
      the impact of oil spillage and activities of oil exploration and production on
      organisms in the immediate environment suggest this.

PMID- 18320333
TI  - Expression change of beta-1,4 galactosyltransferase I, V mRNAs and
      Galbeta1,4GlcNAc group in rat sciatic nerve after crush.
AB  - Glycosylation is one of the most important post-translational modifications. It
      is clear that the single step of beta-1,4-galactosylation is performed by a
      family of beta-1,4-galactosyltransferases (beta-1,4-GalTs), and that each member
      of this family may play a distinct role in different tissues and cells. beta-1,4
      GalT I and V are involved in the biosynthesis of N-linked oligosaccharides. In
      the present study, Real-time PCR revealed that the beta-1,4-GalT I and V mRNAs
      reached peaks at 2 w after sciatic nerve crush. In situ hybridization showed that
      at 1 d after sciatic nerve crush, the expression levels of beta-1,4-GalT I and V
      mRNAs were strong at the crush site, and decreased gradually from crush site to
      the distal segments. In addition, combined in situ hybridization for beta1,4-GalT
      I and V mRNAs and immunohistochemistry for S100 showed that beta1,4-GalT I and V
      mRNAs were mainly located in Schwann cells. Lectin blot showed that the
      expression of Galbeta1,4GlcNAc group increased at 6 h immediately, reached a peak
      at 12 h and remained elevated up to 4 w after sciatic nerve crush. In conclusion,
      beta1,4-GalT I and V might play important roles in the regeneration of the
      injured sciatic nerve, and upregulation of Galbeta1,4GlcNAc group might be
      correlated with the process of the sciatic nerve injury.

PMID- 18320334
TI  - Cross-bridge kinetics of fast and slow fibres of cat jaw and limb muscles:
      correlations with myosin subunit composition.
AB  - Mechanical properties of the jaw-closing muscles of the cat are poorly
      understood. These muscles are known to differ in myosin and fibre type
      compositions from limb muscles. This work aims to correlate mechanical properties
      of single fibres in cat jaw and limb muscles with their myosin subunit
      compositions. The stiffness minimum frequency, f(min), which reflects isometric
      cross-bridge kinetics, was measured in Ca(2+)-activated glycerinated fast and
      slow fibres from cat jaw and limb muscles for temperatures ranging between 15 and
      30 degrees C by mechanical perturbation analysis. At 15 degrees C, f(min) was 0.5
      Hz for limb-slow fibres, 4-6 Hz for jaw-slow fibres, and 10-13 Hz for limb-fast
      and jaw-fast fibres. The activation energy for f(min) obtained from the slope of
      the Arrhenius plot for limb-slow fibres was 30-40% higher than values for the
      other three types of fibres. SDS-PAGE and western blotting using highly specific
      antibodies verified that limb-fast fibres contained IIA or IIX myosin heavy chain
      (MyHC). Jaw-fast fibres expressed masticatory MyHC while both jaw-fast and jaw
      slow fibres expressed masticatory myosin light chains (MLCs). The nucleotide
      sequences of the 3' ends of the slow MyHC cDNAs isolated from cat masseter and
      soleus cDNA libraries showed identical coding and 3'-untranslated regions,
      suggesting that jaw-slow and limb-slow fibres express the same slow MyHC gene. We
      conclude that the isometric cross-bridge cycling kinetics of jaw-fast and limb
      fast fibres detected by f(min) are indistinguishable in spite of differences in
      MyHC and light chain compositions. However, jaw-slow fibres, in which the same
      slow MyHCs are found in combination with MLCs of the jaw type, show enhanced
      cross-bridge cycling kinetics and reduced activation energy for cross-bridge
      detachment.

PMID- 18320335
TI  - Quantification and site-specification of the support practice factor when mapping
      soil erosion risk associated with olive plantations in the Mediterranean island
      of Crete.
AB  - Due to inappropriate agricultural management practices, soil erosion is becoming
      one of the most dangerous forms of soil degradation in many olive farming areas
      in the Mediterranean region, leading to significant decrease of soil fertility
      and yield. In order to prevent further soil degradation, proper measures are
      necessary to be locally implemented. In this perspective, an increase in the
      spatial accuracy of remote sensing datasets and advanced image analysis are
      significant tools necessary and efficient for mapping soil erosion risk on a fine
      scale. In this study, the Revised Universal Soil Loss Equation (RUSLE) was
      implemented in the spatial domain using GIS, while a very high resolution
      satellite image, namely a QuickBird image, was used for deriving cover management
      (C) and support practice (P) factors, in order to map the risk of soil erosion in
      Kolymvari, a typical olive farming area in the island of Crete, Greece. The
      results comprised a risk map of soil erosion when P factor was taken uniform
      (conventional approach) and a risk map when P factor was quantified site
      specifically using object-oriented image analysis. The results showed that the
      QuickBird image was necessary in order to achieve site-specificity of the P
      factor and therefore to support fine scale mapping of soil erosion risk in an
      olive cultivation area, such as the one of Kolymvari in Crete. Increasing the
      accuracy of the QB image classification will further improve the resulted soil
      erosion mapping.

PMID- 18320336
TI  - Continuous water quality monitoring for the hard clam industry in Florida, USA.
AB  - In 2000, Florida's fast-growing hard clam aquaculture industry became eligible
      for federal agricultural crop insurance through the US Department of Agriculture,
      but the responsibility for identifying the cause of mortality remained with the
      grower. Here we describe the continuous water quality monitoring system used to
      monitor hard clam aquaculture areas in Florida and show examples of the data
      collected with the system. Systems recording temperature, salinity, dissolved
      oxygen, water depth, turbidity and chlorophyll at 30 min intervals were installed
      at 10 aquaculture lease areas along Florida's Gulf and Atlantic coasts. Six of
      these systems sent data in real-time to a public website, and all 10 systems
      provided data for web-accessible archives. The systems documented environmental
      conditions that could negatively impact clam survival and productivity and
      identified biologically relevant water quality differences among clam aquaculture
      areas. Both the real-time and archived data were used widely by clam growers and
      nursery managers to make management decisions and in filing crop loss insurance
      claims. While the systems were labor and time intensive, we recommend adjustments
      that could reduce costs and staff time requirements.

PMID- 18320337
TI  - Structural features of diverse ligands influencing binding affinities to estrogen
      alpha and estrogen beta receptors. Part I: Molecular descriptors calculated from
      minimal energy conformation of isolated ligands.
AB  - We report a neural network modeling approach combined with genetic algorithm for
      prediction of experimental binding affinity to human Estrogen Receptor alpha and
      beta (ER-alpha and ER-beta) of a diverse set of chemicals. The counterpropagation
      artificial neural network is used as a modeling method. Structural features of
      ligands having the strongest influence to the binding affinities were
      investigated. The molecular descriptors have been selected in the variable
      selection procedure based on the genetic algorithm (GA). The 3D descriptors of
      molecular structures were calculated for the minimal energy conformation of
      isolated ligands. All the optimized models were tested by an internal and an
      external set of compounds. The models served for classification and prediction of
      binding affinities. The optimized models were 100% correct in the classification
      part, where the active molecules were separated from the inactive ones. The best
      predictive model of active molecules was assessed with the internal test set
      yielding the error in prediction RMS = 0.12, while the predictions for the
      external test set contain some outliers, which are ascribed to the
      incompatibility of individual compounds concerning the structural domain of our
      model. The influence of the receptor on the conformation of the ligands in the
      ligand-protein complex is described and discussed in the accompanying paper.

PMID- 18320338
TI  - Cytokinin vectors mediate marker-free and backbone-free plant transformation.
AB  - Conventional Agrobacterium-mediated transformation methods rely on complex and
      genotype-specific tissue culture media for selection, proliferation, and
      regeneration of genetically modified cells. Resulting transgenic plants may not
      only contain selectable marker genes but also carry fragments of the vector
      backbone. Here, we describe a new method for the production of transgenic plants
      that lack such foreign DNA. This method employs vectors containing the bacterial
      isopentenyltransferase (ipt) gene as backbone integration marker. Agrobacterium
      strains carrying the resulting ipt gene-containing "cytokinin" vectors were used
      to infect explants of various Solanaceous plant species as well as canola
      (Brassica napus). Upon transfer to hormone-free media, 1.8% to 9.9% of the
      infected explants produced shoots that contained a marker-free T-DNA while
      lacking the backbone integration marker. These frequencies often equal or exceed
      those for backbone-free conventional transformation.

PMID- 18320339
TI  - Expression of modified gene encoding functional human alpha-1-antitrypsin protein
      in transgenic tomato plants.
AB  - Transgenic plants offer promising alternative for large scale, sustainable
      production of safe, functional, recombinant proteins of therapeutic and
      industrial importance. Here, we report the expression of biologically active
      human alpha-1-antitrypsin in transgenic tomato plants. The 1,182 bp cDNA sequence
      of human AAT was strategically designed, modified and synthesized to adopt codon
      usage pattern of dicot plants, elimination of mRNA destabilizing sequences and
      modifications around 5' and 3' flanking regions of the gene to achieve high-level
      regulated expression in dicot plants. The native signal peptide sequence was
      substituted with modified signal peptide sequence of tobacco (Nicotiana tabacum)
      pathogenesis related protein PR1a, sweet potato (Ipomoea batatas) sporamineA and
      with dicot-preferred native signal peptide sequence of AAT gene. A dicot
      preferred translation initiation context sequence, 38 bp alfalfa mosaic virus
      untranslated region were incorporated at 5' while an endoplasmic reticulum
      retention signal (KDEL) was incorporated at 3' end of the gene. The modified gene
      was synthesized by PCR based method using overlapping oligonucleotides. Tomato
      plants were genetically engineered by nuclear transformation with Agrobacterium
      tumefaciens harbouring three different constructs pPAK, pSAK and pNAK having
      modified AAT gene with different signal peptide sequences under the control of
      CaMV35S duplicated enhancer promoter. Promising transgenic plants expressing
      recombinant AAT protein upto 1.55% of total soluble leaf protein has been
      developed and characterized. Plant-expressed recombinant AAT protein with
      molecular mass of around approximately 50 kDa was biologically active, showing
      high specific activity and efficient inhibition of elastase activity. The
      enzymatic deglycosylation established proper glycosylation of the plant-expressed
      recombinant AAT protein in contrast to unglycosylated rAAT expressed in E. coli (
      approximately 45 kDa). Our results demonstrate feasibility for high-level
      expression of biologically active, glycosylated human alpha-1-antitrypsin in
      transgenic tomato plants.

PMID- 18320340
TI  - The efficacy of the addition of short-term desmopressin to alarm therapy in the
      treatment of primary nocturnal enuresis.
AB  - OBJECTIVE: The purpose was to evaluate the efficacy of the addition of short-term
      desmopressin to enuretic alarm in patients with primary monosymptomatic nocturnal
      enuresis (PMNE). MATERIALS AND METHODS: A total of 58 [corrected] children with
      PMNE were included in this study. The patients were randomized into two groups.
      In group 1 (n=30), the patients were given 6 weeks of additional oral
      desmopressin to 12 weeks of enuretic alarm therapy, as a single dose of 0.2 mg at
      the first 3 weeks and 0.4 mg at the following 3 weeks. In group 2 (n=28), the
      patients were given 12 weeks of enuretic alarm therapy alone. According to the
      number of wet nights after 12 weeks of treatment, the patients were defined as
      complete responders (dry or more than 75% reduction in wet nights), partial
      responders (50 to 75% reduction) and non-responders (less than 50% reduction).
      Relapse was defined as the reappearance of >1 wet night per week for complete
      responders and >50% increase in pre-treatment wetting frequency for partial
      responders, and all these patients were called relapsers. RESULTS: The mean
      number of wet nights after 3 and 6 weeks treatment was significantly lower in
      group 1 compared to group 2. However, there was no significant difference between
      the groups regarding the mean number of wet nights after 12 and 24 weeks of
      treatment. There was no significant difference between the groups regarding the
      number of responders, partial responders, non-responders and relapsers. In the
      group with additional desmopressin therapy given, the number of patients who
      abandoned therapy was lower than the alarm therapy alone group, but it was not
      statistically significant. CONCLUSION: Our data showed that the addition of short
      term desmopressin to alarm therapy was more effective only in the period when it
      was given, and it did not change the response to alarm therapy in the long term.

PMID- 18320341
TI  - "Limited" double dorsal dartos flap coverage. An effective alternative to
      conventional flap coverage of the neourethra following Mathieu repair for
      subcoronal hypospadias.
AB  - OBJECTIVES: Double dorsal dartos flap coverage of the neourethra has been
      reported to be superior to single flap coverage for the prevention of
      urethrocutaneous fistula following hypospadias surgery. Conventional flap
      coverage involves covering the entire neourethra with vascularised flap. We
      describe a "limited" double dorsal dartos flap coverage of the neourethra
      following Mathieu repair for subcoronal hypospadias. MATERIALS AND METHODS: In a
      prospective study conducted between Feb 2003 and Feb 2007, 31 patients with
      primary subcoronal hypospadias who had a flat and narrow urethral plate with a
      healthy urethral meatus and minimal or no chordee underwent Mathieu hypospadias
      repair. A "limited" double dorsal dartos flap coverage of the neourethra was done
      in all patients. This involved covering only that portion of the neourethra which
      remained exposed after glans closure, i.e. the proximal neourethra. Primary
      surgical outcome assessed was the development of urethrocutaneous fistula
      following surgery. RESULTS: The mean age at the time of repair was seven years
      and mean follow up was eight months. There was no flap loss, urethrocutaneous
      fistula formation, or glanular dehiscence in any of the 31 patients. One patient
      developed meatal stenosis which was managed by dilatation. One patient developed
      superficial sloughing of the penile skin. Overall complication rate was 6.45%.
      CONCLUSION: "Limited" double dorsal dartos flap coverage of the neourethra seems
      to be an effective method to reduce the fistulous complication rate following
      Mathieu repair for subcoronal hypospadias. A larger comparative study needs to be
      done to evaluate conventional neourethral coverage with "limited" neourethral
      coverage.

PMID- 18320342
TI  - Ureterointestinal strictures following Bricker ileal conduit: management via a
      percutaneous approach.
AB  - OBJECTIVE: Urinary diversion after radical cystectomy is commonly performed via
      an ileal conduit using the Bricker method. However, 4-8% of these cases are
      complicated with stricture formation at the ureterointestinal junction. Thus,
      this could eventually lead to hydronephrosis and kidney loss in neglected
      patients. Few data exist concerning the outcomes of patients with
      ureterointestinal junction strictures managed via a percutaneous approach and
      balloon dilatation of the stricture. The potential of managing these strictures,
      using a stent replacement strategy, was evaluated. PATIENTS AND METHODS: A total
      of 14 patients (10 male, 4 female; age range 24-72 years) were enrolled in the
      study. Mean follow-up time was 30.9 months. Invasive bladder cancer was diagnosed
      in 11, neurogenic bladder in 2 and shrunk bladder after external beam radiation
      for prostate cancer in 1 patient. They were all managed by radical cystectomy
      followed by Bricker ileal conduit. In 6 cases, ureterointestinal strictures
      bilaterally were discovered, whereas unilateral (left-sided) strictures were
      noted to the remaining 8 patients. All strictures were managed via a percutaneous
      approach and balloon dilatation. A double J stent was placed at the end of the
      procedure and was regularly replaced after an interval of 3-6 months. RESULTS: A
      percutaneous nephrostomy was successfully placed in all patients. Double J stent
      insertion was possible in 18 of a total of 20 (90%) obstructed ureters. No major
      complications were observed in any of the cases while adequate renal function was
      preserved in all patients. Quality of life is not reported to be significantly
      compromised in any patient. Double J ureteral stent replacement is performed
      every 3-6 months in a retrograde fashion. One patient died in the follow-up
      period due to disease progression. CONCLUSION: Placement of a double J stent via
      a percutaneous approach seems to have offered a viable option in the management
      of ureterointestinal strictures in this patient population. In addition,
      periodical retrograde replacement of the stent probably does not constitute a
      factor compromising quality of life. However, further studies are required to
      justify these primary clinical data.

PMID- 18320343
TI  - Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1
      receptor blockade on apoptotic changes in contralateral testis following
      unilateral testicular torsion.
AB  - OBJECTIVES: In this experimental study, our aim was to determine whether
      angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 (AT1)
      receptor blockade affect the apoptotic changes in contralateral testis following
      unilateral testicular torsion (UTT). METHODS: Study groups consisted of 30 adult
      male Wistar rats. The rats were randomly separated into five groups. Group 1 was
      maintained as control without manipulation. Group 2 underwent the sham operation.
      Torsion was created by rotating the left testis 720 degrees clockwise for 4 h and
      maintained by fixing the testis to the scrotum in the other groups. Group 3
      underwent torsion and detorsion, with saline administration after detorsion. In
      group 4, the same surgical procedure was done as in the detorsion group, but AT1
      receptor blocker (losartan 30 mg/kg) was injected intraperitoneally for 60 min
      before detorsion. In group 5, the same surgical procedure was done as in the
      detorsion group, but ACE inhibitor (lisinopril 50 mg/kg) was injected
      intraperitoneally for 60 min before detorsion. Bilateral testes were removed from
      each rat 24 h after surgery. Apoptosis was assessed in paraffin-embedded sections
      stained for TUNEL method. Reticulum staining was performed to evaluate the
      extracellular changes semiquantitatively. Testicular biopsy score counts were
      performed on these sections according to Johnsen. RESULTS: The mean apoptotic
      scores of group 1, group 2 and group 3 were significantly higher than that of the
      other groups. There was no difference between the apoptotic scores of groups 1,
      2, 4 and 5. Reticulum stain was increased in group 3 as compared to other groups.
      The mean Johnsen biopsy score of group 3 was significantly lower than that of the
      other groups. CONCLUSION: ACE inhibition and AT1 receptor blockade reduced the
      tubular damage and apoptosis in the contralateral testes after UTT. The
      beneficial effect of these drugs may arise from inhibition of ischemic process
      resulting from increased sympathetic activity and elimination of insults
      subsequent to dysregulation of RAS. These results suggest that ACE inhibitors and
      AT1 receptor blockers may be of potential value in patients with UTT.

PMID- 18320344
TI  - Evolutionary flux of potentially bldA-dependent Streptomyces genes containing the
      rare leucine codon TTA.
AB  - Previous studies have shown that one of the six leucine codons, UUA, is rare in
      Streptomyces, and that, while the gene for the UUA-specific tRNA, bldA, can
      generally be inactivated in diverse streptomycetes without impairing vegetative
      growth, bldA mutants are typically defective in reproductive aerial growth and in
      antibiotic production. Here, four complete genome sequences and 143 gene clusters
      for antibiotic biosynthesis from diverse streptomycetes were analysed in order to
      evaluate the evolution and function of genes whose possession of TTA codons makes
      them dependent on bldA. It was deduced that the last common ancestor of the four
      sequenced genomes, possibly 220 million years ago, already possessed the bldA
      system, together with perhaps 200 TTA-containing target genes. Some 33 of these
      genes are retained by the modern descendants, though only three of them retain a
      TTA in all occurrences. Nearly all of these 33, as well as many of the TTA
      containing genes with orthologues in two or three of the four genomes, have the
      same location on the chromosomes as in their common ancestor. However, the
      majority of TTA-containing genes (61% overall in the four genomes) are species
      specific, and were probably acquired by comparatively recent horizontal gene
      transfer. Most of these genes are of unknown function, and it is likely that many
      of them confer specialised ecological benefits. On the other hand, one class of
      species-specific, functionally recognisable, horizontally acquired genes--the
      gene clusters for antibiotic production--very often contain TTA codons; and
      nearly half of them have TTA codons in their pathway-specific regulatory genes.

PMID- 18320345
TI  - Antimicrobial susceptibility and invasive ability of Staphylococcus aureus
      isolates from mastitis from dairy backyard systems.
AB  - Fifteen (15) backyard farms were investigated to determine the antimicrobial
      susceptibility and invasion ability of S. aureus isolates from cows with
      subclinical mastitis in Mexico. A total of 106 cows were sampled and 31 S. aureus
      isolates were recovered. S. aureus isolates were resistant to penicillin class
      antibiotics and susceptible to gentamicin and cetyltrimethylammonium bromide.
      STA9 and STA13 isolates were resistant to erythromycin (MIC > 25 microg/ml) and
      lincomycin (STA13, MIC > 25 microg/ml; STA9, MIC > 100 microg/ml). STA9 isolate
      harbors the erm(B) and msr(A) genes, whereas STA13 isolate harbors the erm(C)
      gene. STA9 and STA13 isolates contains the lnu(A) gene. Only 5 isolates (STA11,
      STA13, STA14, STA15 and STA21) were able to internalize in bovine mammary
      epithelial cells. These results indicate that S. aureus isolates from dairy
      backyard farms showed differences in the antimicrobial susceptibility patterns
      and invasion ability in bovine mammary epithelial cells. This kind of evaluations
      should be performed in different dairy regions, since resistance patterns and
      isolate diversity vary on a per-region basis.

PMID- 18320346
TI  - A comparative study of candidal invasion in rabbit tongue mucosal explants and
      reconstituted human oral epithelium.
AB  - The purpose of this study is to compare the light and scanning electron
      microscopic (SEM) features of tissue invasion by three Candida species (C.
      albicans, C. tropicalis, and C. dubliniensis) in two different tissue culture
      models: rabbit tongue mucosal explants (RTME) and reconstituted human oral
      epithelium (RHOE). Tongue mucosal biopsies of healthy New Zealand rabbits were
      maintained in explant culture using a transwell system. RHOE was obtained from
      Skinethic Laboratory (Nice, France). RTME and RHOE were inoculated with C.
      albicans, C. tropicalis, and C. dubliniensis separately and incubated at 37
      degrees C, 5% CO(2), and 100% humidity up to 48 h. Light microscopic and SEM
      examinations of uninfected (controls) and infected tissues were performed at 24
      and 48 h. C. albicans produced characteristic hallmarks of pathological tissue
      invasion in both tissue models over a period of 48 h. Hyphae penetrated through
      epithelial cells and intercellular gaps latter resembling thigmotropism. SEM
      showed cavitations on the epithelial cell surfaces particularly pronounced at
      sites of hyphal invasion. Some hyphae on RTME showed several clusters of
      blastospores attached in regular arrangements resembling "appareil sporifere". C.
      tropicalis and C. dubliniensis produced few hyphae mainly on RTME but they did
      not penetrate either model. Our findings indicate that multiple host-fungal
      interactions such as cavitations, thigmotropism, and morphogenesis take place
      during candidal tissue invasion. RTME described here appears to be useful in
      investigations of such pathogenic processes of Candida active at the epithelial
      front.

PMID- 18320347
TI  - Occurrence of Antibodies to Paracoccidioides brasiliensis in dairy cattle from
      Mato Grosso do Sul, Brazil.
AB  - The aim of this study was to evaluate the humoral immune response in cattle
      immunized with Paracoccidioides brasiliensis and perform a seroepidemiological
      study of paracoccidioidomycosis in dairy cattle from Mato Grosso do Sul. Two
      animals (one steer and one heifer) were inoculated with a suspension of P.
      brasiliensis in Freund incomplete adjuvant. Blood samples were collected
      periodically to evaluate humoral immune response by immunodiffusion and ELISA,
      using exoantigen and gp43 as antigens, respectively. The antibody production was
      detected by immunodiffusion and ELISA, in both animals, 14 days after
      immunization. The soroepidemiologic study was carried out in 400 cattle of Mato
      Grosso do Sul from four municipalities: Corumba, Dourados, Nova Andradina, and
      Sao Gabriel d'Oeste. The municipalities of Corumba (30%) and Nova Andradina (28%)
      showed higher positivity than Dourados (8%) and Sao Gabriel d'Oeste (4%). In this
      study we concluded that cattle immunized with P. brasiliensis develop humoral
      immune response for gp43, remaining with high titers of antibodies, and that this
      animal species could be an epidemiologic marker of paracoccidioidomycosis.

PMID- 18320348
TI  - Dimorphism, thermal tolerance, virulence and heat shock protein 70 transcription
      in different isolates of Paracoccidioides brasiliensis.
AB  - The mycelia-to-yeast (M-Y) transition, thermal tolerance and virulence profiles
      were evaluated for nine isolates of Paracoccidioides brasiliensis, including
      samples from two of the three recently discovered cryptic species, as well as
      their relation to the partial sequence and transcription of the hsp70 gene. The
      isolates Bt84 and T10 (from PS2 species) took more time to convert to yeast form
      and presented elongated yeast cells at 36 degrees C. Arthroconidia production was
      also observed during the M-Y transition for some isolates. Our data confirm that
      the hsp70 transcription may be associated with thermal tolerance, but this does
      not seem to be directly related to high virulence profiles. The partial
      sequencing of this gene allowed the separation of our isolates into two clusters
      that correspond to the two sympatric cryptic species occurring in an area
      hyperendemic for PCM (Botucatu, SP, Brazil).

PMID- 18320349
TI  - Thinking across species--a critical bioethics approach to enhancement.
AB  - Drawing upon a concept of 'critical bioethics' [7] this paper takes a species
      broad approach to the social and ethical aspects of enhancement. Critical
      Bioethics aims to foreground interdisciplinarity, socio-political dimensions, as
      well as reflexivity to what becomes bioethical subject matter. This paper focuses
      upon the latter component and uses the example of animal enhancement as a way to
      think about both enhancement generally, and bioethics. It constructs several
      arguments for including animal enhancement as a part of enhancement debates, and
      considers some connections between human and animal enhancement. The paper
      concludes in a plea for an 'enhancement' to our critical abilities to examine
      some of the underlying social, moral and ethical assumptions bound up in varied
      anticipated 'enhanced' futures.

PMID- 18320350
TI  - The adaptation into Spanish of the Coddington Life Events Scales (CLES).
AB  - AIMS: To obtain a conceptually and psychometrically equivalent Spanish version of
      the Coddington Life Events Scales (CLES) for children and adolescents and to test
      their psychometric properties. METHODS: Forward and backward translations were
      performed. Comprehension, acceptability, and alternative translations were tested
      in focus groups and semi-structured interviews. An expert panel and the copyright
      holders of the original version were actively involved. Test-retest reliability
      [Intraclass Correlation Coefficient (ICC)] was assessed by administering the
      questionnaire on two occasions 3 months apart to children aged 12-14 years (n =
      30). Construct validity was assessed by comparing children's responses with those
      of their parents (n = 19). The methods replicated those of the validation of the
      original version. RESULTS: Of the 53 CLES items translated, ten were found to be
      difficult to understand. Following back-translation, seven items were modified
      and a final version was obtained. Test-retest ICC reliability for total scores
      was 0.63. The ICC between children and parents was 0.42. Both results were very
      similar to those reported for the original version. CONCLUSIONS: These
      preliminary findings suggest that the Spanish version of the CLES is
      understandable and acceptable and that it is similar to the original in terms of
      validity and reliability. Although further validation is needed, it is
      recommended for use in research settings in Spain.

PMID- 18320351
TI  - The effects of exercise training on quality of life in HAART-treated HIV-positive
      Rwandan subjects with body fat redistribution.
AB  - OBJECTIVE: Our objective was to examine the effects of exercise training (EXS) on
      quality of life (QoL) in highly active antiretroviral therapy (HAART)-treated HIV
      positive (HIV+) subjects with body fat redistribution (BFR) in Rwanda. METHODS:
      The effects of a randomised controlled trial of EXS on QoL were measured using
      World Health Organisation Quality of Life (WHOQOL)-BREF in HIV+ subjects with BFR
      randomised to EXS (n = 50; BFR + EXS) or no exercise training (n = 50; BFR +
      noEXS). RESULTS: At 6 months, scores on the psychological [1.3 (0.3) vs. 0.5
      (0.1); P < 0.0001], independence [0.6 (0.1) vs. 0.0 (0.0); P < 0.0001], social
      relationships [0.6 (0.2) vs. 0.0 (0.0); P < 0.0001] and HIV HAART-specific QoL
      domains [1.4 (0.2) vs. -0.1 (0.2); P < 0.0001] improved more in BFR + EXS than
      BFR + noEXS group, respectively. Self-esteem [1.3 (0.8) vs. 0.1 (0.6); P <
      0.001], body image [1.5 (0.6) vs. 0.0 (0.5); P < 0.001] and emotional stress [1.6
      (0.7) vs. 0.2 (0.5); P < 0.001] improved more in the BFR + EXS group than BFR +
      noEXS group, respectively. Psychological [1.5 (0.2) vs. 1.1 (0.3); P < 0.0001],
      social relationship [0.8 (0.2) vs. 0.4 (0.2); P < 0.0001], and HIV HAART-specific
      well-being [1.8 (0.2) vs. 1.0 (0.0); P < 0.0001] improved more in BFR + EXS
      female than male subjects. CONCLUSIONS: Exercise training improved several
      components of QoL in HAART-treated HIV+ African subjects with BFR. Exercise
      training is an inexpensive and efficacious strategy for improving QoL in HIV+
      African subjects, which may improve HAART adherence and treatment initiatives in
      resource-limited areas of sub-Saharan Africa.

PMID- 18320352
TI  - Quantification of the level descriptors for the standard EQ-5D three-level system
      and a five-level version according to two methods.
AB  - OBJECTIVES: Our aim was to compare the quantitative position of the level
      descriptors of the standard EQ-5D three-level system (3L) and a newly developed,
      experimental five-level version (5L) using a direct and a vignette-based indirect
      method. METHODS: Eighty-two respondents took part in the study. The direct method
      represented a visual analog scale (VAS) rating of the nonextreme level
      descriptors for each dimension and each instrument separately. The indirect
      method required respondents to score 15 health scenarios with 3L, 5L and a VAS
      scale. Investigated were: (1) equidistance (Are 3L and 5L level descriptors
      distributed evenly over the VAS continuum?); (2) isoformity (Do the identical
      level descriptors on 3L and 5L yield similar results?); and (3) consistency
      between dimensions (Do the positions of similar level descriptors differ across
      dimensions within instruments?). RESULTS: Equidistance without transformation was
      rejected for all dimensions for both 3L and 5L but satisfied for 5L after
      transformation. Isoformity gave mixed results. Consistency between dimensions was
      satisfied for both instruments and both methods. DISCUSSION: The level
      descriptors have similar distributions across comparable dimensions within each
      system, but the pattern differs between 3L and 5L. This methodological study
      provides evidence of increased descriptive power and a broadened measurement
      continuum that encourages the further development of an official five-level EQ
      5D.

PMID- 18320353
TI  - Effects of freezing on bone histological morphology.
AB  - Allograft bone has been widely used for reconstruction of different portions of
      the skeleton. The fragment of bone harvested must be kept under low temperatures.
      The cryopreservation also contributes to decrease the antigenic potential of the
      tissue. Although this technique is considered safe, there is little information
      about the morphological modifications that the medullary and cortical portions of
      bone suffer after freezing. Hence, the aim of this study was to investigate the
      morphology of bone tissue after freezing under different temperatures and
      periods. Twelve rabbits were used to analyze the effects of two temperatures, -20
      degrees C and -70 degrees C, during four periods of time: 30, 60, 90, 120 days.
      Tissues were analyzed by HE, picro-sirius stains and also by Feulgen's reaction,
      through qualitative and morphometric ways, considering the area occupied by cells
      and nuclei, medullary and cortical portions, as well as by collagen expression at
      cortical. The differences among the treatments were analyzed by Tukey s test, at
      5% significance level. Bone freezing increased cellular and nuclear areas at
      cancellous bone and diminished nuclear area at the cortical bone. Cortical bone
      collagen suffered denaturation proportionally to temperature decrease and to
      freezing duration. These alterations compromised the morphology of tissues after
      90 or 120 days of freezing at the temperature of -70 degrees C. Cells necrosed
      during freezing, contributing to reduce bone antigenicity.

PMID- 18320354
TI  - Validation of 15 kGy as a radiation sterilisation dose for bone allografts
      manufactured at the Queensland Bone Bank: application of the VDmax 15 method.
AB  - BACKGROUND: ISO 11137-2006 (ISO 11137-2a 2006) provides a VDmax 15 method for
      substantiation of 15 kGy as radiation sterilisation dose (RSD) for health care
      products with a relatively low sample requirement. Moreover, the method is also
      valid for products in which the bioburden level is less than or equal to 1.5. In
      the literature, the bioburden level of processed bone allografts is extremely
      low. Similarly, the Queensland Bone Bank (QBB) usually recovers no viable
      organisms from processed bone allografts. Because bone allografts are treated as
      a type of health care product, the aim of this research was to substantiate 15
      kGy as a RSD for frozen bone allografts at the QBB using method VDmax 15-ISO
      11137-2: 2006 (ISO 11137-2e, Procedure for method VDmax 15 for multiple
      production batches. Sterilisation of health care products - radiation - part 2:
      establishing the sterilisation dose, 2006; ISO 11137-2f, Procedure for method
      VDmax 15 for a single production batch. Sterilisation of health care products -
      radiation - part 2: establishing the sterilisation dose, 2006). MATERIALS: 30
      femoral heads, 40 milled bone allografts and 40 structural bone allografts
      manufactured according to QBB standard operating procedures were used. METHOD:
      Estimated bioburdens for each bone allograft group were used to calculate the
      verification doses. Next, 10 samples per group were irradiated at the
      verification dose, sterility was tested and the number of positive tests of
      sterility recorded. If the number of positive samples was no more than 1, from
      the 10 tests carried out in each group, the verification was accepted and 15 kGy
      was substantiated as RSD for those bone allografts. RESULTS: The bioburdens in
      all three groups were 0, and therefore the verification doses were 0 kGy.
      Sterility tests of femoral heads and milled bones were all negative (no
      contamination), and there was one positive test of sterility in the structural
      bone allograft. Accordingly, the verification was accepted. CONCLUSION: Using the
      ISO validated protocol, VDmax 15, 15 kGy was substantiated as RSD for frozen bone
      allografts manufactured at the QBB.

PMID- 18320355
TI  - Apoptosis in fresh and cryopreserved cardiac valves of pig samples.
AB  - To analyse the influence of cold ischemic time (CIT) (2-24 h) and of
      cryopreservation (liquid phase) on the viability of the valvular fibroblasts and
      in the presence of apoptosis. Cardiac valves from 10 pigs were evaluated by
      anatomo-pathological study of the wall, muscle and leaflet. At the same time, the
      presence of cellular death due to apoptosis was investigated in two ways;
      directly on tissue by Apodetec system and by two-colour flow cytometry assay
      analyzing a suspension of fibroblast from valve leaflets using Anexina V and
      propidium iodure (PI). We established three groups of samples to compare
      different experimental conditions: 2 h of ischemia (group 1), 24 h of ischemia
      (group 2), and a programme of cryopreservation (-1 degrees C/min) after 2 h of
      ischemia, followed by storage in liquid nitrogen during a week and thawing was
      performed (group 3). The analysis of viabilities showed slight differences
      between all three groups. The results indicated CIT of 24 h undergoing more
      structural affectation than CIT of 2 h. Flow cytometry analysis did not show
      important differences between groups; however cryopreserved samples (group 3)
      slightly less viability and a higher percentage of death by apoptosis than group
      1 and 2 using flow cytometry. Apoptosis was confirmed on tissue from all valves
      but mainly in samples of group 2 and group 3. In summary, the viability of the
      valves in the case of ischemic times of 2 h, 24 h or after
      cryopreservation/thawing differs slightly. The death of the cells is mainly
      mediated by necrosis and not by apoptosis.

PMID- 18320356
TI  - Promoter sequence variants of LIGHT are associated with female vascular dementia.
AB  - LIGHT (homologous to L ymphotoxins, exhibits I nducible expression, and competes
      with herpes simplex virus G lycoprotein D for H erpes virus entry mediator, a
      receptor expressed by T lymphocytes) is implicated in the inflammation by
      disrupted T cell homeostasis, primarily at a transcriptional level. We
      investigated the association of LIGHT promoter with ischemic stroke and vascular
      dementia induced by such inflammation. We determined transcription factor binding
      sites altered by promoter SNPs using transcription factor prediction programs.
      Six common haplotypes composed of the selected SNPs (C-770T, G-607T, G-543A, and
      A-399G) were used for the assay of reporter activity. The most frequent haplotype
      construct, CGGA, induced the highest luciferase activity. The haplotype TTGA
      showed the lowest expression with 0.39-fold activity (P < 0.001) of CGGA. The
      substitution from C to T at the locus of C-770T (TGGA) decreased the reporter
      activity by 47% (P < 0.001). The SNPs and haplotypes were further investigated to
      see their association with ischemic stroke and vascular dementia in 455 controls
      and 478 patients. Significant association with vascular dementia was shown in the
      allele T of C-770T (odds ratio [OR] = 1.54; P < 0.05) and the haplotype TTGA (OR
      = 10.59; P < 0.05) in females. We concluded that the allele T of C-770T and the
      haplotype TTGA of the promoter SNPs in LIGHT gene might decrease the expression
      of LIGHT and subsequently increase the susceptibility to vascular dementia in
      females.

PMID- 18320357
TI  - Genetic variation in heat shock protein 60 gene and coronary heart disease in
      China: tagging-SNP haplotype analysis in a case-control study.
AB  - BACKGROUND: High levels of circulating heat shock protein 60 (Hsp60) and antibody
      to human Hsp60 have been associated with greater risk of coronary heart disease
      (CHD) in several studies, but associations between polymorphisms of the hsp60
      gene and CHD risk have not been investigated. METHODS: By resequencing DNA from
      30 unrelated Han Chinese and using HapMap Phase I Chinese data of hsp60 gene, we
      selected four tagging single nucleotide polymorphisms (tagSNPs) named rs2340690,
      rs788016, rs2305560, and rs2565163, and determined their frequencies in 1,003
      Chinese CHD patients and 1,003 age- and sex-frequency-matched controls.
      Furthermore, we used PHASE 2.0 software to reconstruct haplotypes and logistic
      regression to control for potential confounders in multivariate analyses.
      RESULTS: We found 13 SNPs in hsp60 gene (including four novel SNPs) in Han
      Chinese subjects. Our results showed no significant differences in four selected
      SNPs in patients with CHD and controls after adjusting for other conventional
      risk factors and stratifying by age, sex, smoking status, past history of
      hypertension and DM; however, our results showed that subjects with the GCTC
      haplotype had about twofold higher risk of CHD than those with the GTTC haplotype
      (OR = 1.91, 95%CI: 1.26-2.89, P = 0.002). CONCLUSIONS: Our results suggest that
      the GCTC haplotype in the hsp60 gene is significantly associated with higher CHD
      risk in a Chinese population.

PMID- 18320358
TI  - Response of plasma IL-6 and its soluble receptors during submaximal exercise to
      fatigue in sedentary middle-aged men.
AB  - The pleiotropic cytokine interleukin-6 (IL-6) has been demonstrated to increase
      during exercise. Little is known regarding the response of the soluble IL-6
      receptors (sIL-6R and sgp130) during such exercise. The aim of the current study
      was to investigate the response of plasma IL-6, sIL-6R and sgp130 during
      fatiguing submaximal exercise in humans. Twelve participants underwent an
      incremental exercise test to exhaustion and one week later performed a submaximal
      exercise bout (96 +/- 6% lactate threshold) to volitional exhaustion. Blood
      samples taken at rest and immediately post exercise were analyzed for IL-6, sIL
      6R and sgp130. IL-6 increased (P < 0.01) by 8.4 +/- 8.9 pg ml(-1) (75.7%) during
      the exercise period. sIL-6R and sgp130 also increased (P < 0.05) by 2.7 +/- 3.9
      ng ml(-1) (9.6%) and 37.7 +/- 55.6 ng ml(-1) (9.6%), respectively. The current
      study is the first investigation to demonstrate that alongside IL-6, acute
      exercise stress results in an increase in both sIL-6R and sgp130.

PMID- 18320359
TI  - P-cadherin and beta-catenin are useful prognostic markers in breast cancer
      patients; beta-catenin interacts with heat shock protein Hsp27.
AB  - The cadherin-catenin proteins have in common with heat shock proteins (HSP) the
      capacity to bind/interact proteins of other classes. Moreover, there are common
      molecular pathways that connect the HSP response and the cadherin-catenin protein
      system. In the present study, we have explored whether in breast cancer the HSP
      might interact functionally with the cadherin-catenin cell adhesion system. Beta
      catenin was immunoprecipitated from breast cancer biopsy samples, and the protein
      complexes isolated in this way were probed with antibodies against HSP family
      members. We are thus the first to demonstrate a specific interaction between beta
      catenin and Hsp27. However, beta-catenin did not bind Hsp60, Hsp70, Hsp90, gp96,
      or the endoplasmic reticulum stress response protein CHOP. To confirm the finding
      of Hsp27-beta-catenin interaction, the 27-kDa immunoprecipitated band was excised
      from one-dimensional polyacrylamide gel electrophoresis gels and submitted to
      liquid chromatography-tandem mass spectrometry with electrospray ionization,
      confirming a role for Hsp27. In addition, beta-catenin interacted with other
      proteins including heat shock transcription factor 1, P-cadherin, and caveolin-1.
      In human breast cancer biopsy samples, beta-catenin was coexpressed in the same
      tumor areas and in the same tumor cells that expressed Hsp27. However, this
      coexpression was strong when beta-catenin was present in the cytoplasm of the
      tumor cells and not when beta-catenin was expressed at the cell surface only.
      Furthermore, murine breast cancer cells transfected with hsp25 showed a
      redistribution of beta-catenin from the cell membrane to the cytoplasm. When the
      prognostic significance of cadherin-catenin expression was examined by
      immunohistochemistry in breast cancer patients (n = 215, follow-up = >10 years),
      we found that the disease-free survival and overall survival were significantly
      shorter for patients expressing P-cadherin and for patients showing expression of
      beta-catenin in the cytoplasm only (not at the cell surface). The interactions of
      beta-catenin with Hsp27 and with HSF1 may explain some of the molecular pathways
      that influence tumor cell survival and the clinical significance in the prognosis
      of the breast cancer patients.

PMID- 18320360
TI  - Live images of RNA polymerase II transcription units.
AB  - The nucleus of an amphibian oocyte can be manually isolated in mineral oil where
      it maintains all its activities for several hours. These undisrupted (live)
      nuclei have been used successfully in recent years to analyze the dynamic
      organization of several non-chromosomal nuclear organelles. Here, we describe an
      improved procedure for imaging an oil-isolated nucleus by light microscopy and we
      use it to produce the very first images of lampbrush chromosomes in an in vivo
      like condition. These chromosomes are morphologically identical to those observed
      in conventional nuclear spread preparations. Importantly, their lateral loops,
      which are active RNA polymerase II transcription units, are readily distinguished
      by differential interference contrast microscopy.

PMID- 18320361
TI  - Single-cell c-myc gene expression in relationship to nuclear domains.
AB  - Nuclear locations of the c-myc gene and its transcripts (c-myc (T)) have been
      investigated in relation to nuclear domains involved in RNA synthesis and
      processing. Transcription of the c-myc gene appears to be linked to the late G(1)
      and preferentially to S-phases of the cell cycle. The c-myc gene and its
      transcripts were positioned non-randomly within the interphase nucleus;
      additionally, c-myc RNA signals accumulated at nucleoli. Using oligo-probes,
      designed to exon II and exon III of the c-myc gene, single c-myc (T) was
      preferentially observed in human carcinoma HT29 and A549 cells. Conversely, human
      embryonal teratocarcinoma NTERA cells were characterized by the presence of
      multiple c-myc RNA signals located in both the nucleoli and nucleoplasm. When
      accumulated at nucleoli, c-myc (T) occupied the periphery of this organelle,
      though not those associated with the cultivation surface. In HT29 cells,
      approximately 80% of c-myc (T) co-localized with the RNAP II positive regions, so
      called transcription factories. However, in approximately 20% of the cells with c
      myc transcripts, the c-myc (T) was released from the site of synthesis, and was
      not associated with either transcription factories or SC35 domains. In
      approximately 60% of nuclei with c-myc (T), these signals were located in close
      proximity to the SC35 regions, but promyelocytic leukaemia bodies were associated
      with c-myc (T) only in approximately 20% of the nuclei. Taken together, c-myc RNA
      signals were positioned in the most internal parts of the cell nuclei
      preferentially associated with the nucleoli. Specific nuclear and nucleolar
      positioning probably reflects the kinetics of c-myc RNA metabolism.

PMID- 18320362
TI  - Proceedings from the 8th PEACe Conference on Protein Expression in Animal Cells,
      Angra Dos Reis, Brazil, September 16-20, 2007.

PMID- 18320363
TI  - The efficiency of single agent docetaxel in patients with platinum-refractory non
      small cell lung carcinoma.
AB  - BACKGROUND: To evaluate the efficiency of docetaxel as second line chemotherapy
      in patients with platinum-refractory non-small cell lung carcinoma (NSCLC).
      PATIENTS AND METHODS: Fifty-two patients with locally advanced or metastatic
      NSCLC who had platinum-refractory disease (progressed through or within 3 months
      of completion of first line therapy) and an Eastern Cooperative Oncology Group
      performance (ECOG) status 0-2 were treated with second-line chemotherapy
      consisting of single agent docetaxel (100 mg/m(2), intravenously, on day 1 of a
      21-day cycle). The median number of treatment cycles was 4 (2-6). Disease-free
      (DFS) and overall survival (OS), response rates and toxicity were evaluated.
      RESULTS: The median progression-free survival of patients was 3 months (95% CI:
      0.01-5.99) and overall survival was 7.2 months (95% CI: 2.2-9.5). One-year
      overall survival rate was 29%. Disease control (complete response, partial
      response, or stable disease) was achieved in 25 patients (48%) and overall
      response rate was 13% (7 patients). There were no complete responses. Seventeen
      patients (33%) had stable disease and twenty-seven patients (52%) had progressive
      disease. Age, gender, stage at diagnosis (IIIB vs. IV), performance status at
      initiation of second-line therapy (0-1 vs. 2) histopathological type (epidermoid
      vs. others), grade, LDH, albumin, weight loss were evaluated as prognostic
      factors; however, none of these had a significant affect on survivals. The
      protocol was well tolerated and there were no toxic deaths. Grade III-IV anemia
      was present in 8 patients (15%) and thrombopenia in 12 (23%) patients. The most
      frequent grade 3-4 toxicities were leucopenia (52%) and neutropenia (48%). Febril
      neutropenia occurred in 14 patients (26%). No patients experienced grade III-IV
      mucositis and diarrhea. Totally, the need of a dose reduction was about 25% and
      treatment delay (4-9 days) occurred in 5 patients (10%) and 7 patients (13%),
      respectively, because of toxicity. CONCLUSIONS: Second-line chemotherapy with
      single-agent docetaxel offers a small but significant survival advantage with
      acceptable toxicity for patients with advanced NSCLC who have platinum-refractory
      disease.

PMID- 18320364
TI  - Serum neopterin levels in patients with breast cancer.
AB  - The aim of this study was to determine the importance of serum neopterin level in
      female patients with breast cancer of various clinical stages. The study
      consisted of 75 female patients with breast cancer who were diagnosed and treated
      at the Gazi University Department of Medical Oncology. The patients were
      classified into three representative groups and a control group: group A (n =
      26), patients with newly diagnosed primary breast cancer and without metastasis;
      group B (n = 33), patients with metastatic breast cancer who had undergone
      treatment for their diseases and on whom metastasis was detected during their
      follow-up; group C (n = 16), off-therapy patient whose cancer had been in
      remission for at least 5 years; group D (n = 20) healthy controls. The median
      serum neopterin levels of the 75 patients with breast cancer 11.0 (range, 0-23.6)
      nmol/L were significantly higher than those of controls (8.3 (range, 1.2-12.0)
      nmol/L). In group B patients, neopterin levels (12.6 (range, 0-23.6) nmol/L) were
      statistically significantly higher than those of controls, primary breast cancer
      patients, and off-therapy patients (P < .05). In group B, patients with visceral
      metastases had higher neopterin levels than did those with bone or local
      metastases; however, that difference was not statistically significant. The
      median serum neopterin levels of the primary breast cancer patients in group A
      (8.8 (range, 0-20) nmol/l) were not statistically significantly different from
      those in controls and off-therapy patients. Serum neopterin levels were
      significantly elevated in patients with metastatic breast cancer. Neopterin seems
      to be an indicator of metastatic cancer rather than a marker for local cancer. In
      patients with metastatic breast cancer, determining the serum neopterin levels
      may be useful in estimating survival; however, additional long-term follow-up
      will be needed.

PMID- 18320366
TI  - The use of external fixation in complex trauma of upper limb.
AB  - From 1997 to 2003 (7 years follow-up) we treated 33 complex traumas of the upper
      limbs with the use of external fixation: forearm or humeral complete amputation,
      complex crash, sometimes with hand crash associated. Often a revascularisation
      was necessary like as a secondary skin coverage for soft tissue loss or following
      ischaemic necrosis. Three patients were reluctant to agree to a secondary
      amputation for large soft tissue necrosis and infection. A high percentage of
      cases need a successive operation because of bone non-union. Revision of our
      casistic helps us answer the following: how complex and long is the prognosis of
      this kind of patient, which are the most important choices we have to make, how
      important is the length of time taken to make a decision and what are the weak
      spots in the treatment of these traumas.

PMID- 18320367
TI  - Computer-assisted alignment system for tibial component placement in total knee
      replacement: a radiological study.
AB  - In total knee replacement (TKR), regarding tibial component positioning, almost
      all implants offer both an intramedullary and an extramedullary alignment guide,
      leaving it up to the surgeon which guide to use. However, early failure in TKR
      can be caused by incorrect positioning or orientation with poor limb alignment.
      Recently computer-based alignment systems have been developed to help the surgeon
      to overcome these complications. The Authors retrospectively analysed their
      experience using a computer-based CT-free alignment system. They assessed the
      radiological alignment of the tibial components in 38 computer-assisted TKR 6
      months after surgery. The frontal tibial component angle (FTC) and the sagittal
      orientation of the tibial component (slope) were evaluated 6 months after the
      operation. The results were compared to those achieved with traditional alignment
      systems. The surgical time was statistically longer in the computer-assisted
      group but in this group all the tibial components were aligned within 4 degrees
      of all the ideal measurements in both frontal and sagittal planes.

PMID- 18320368
TI  - Remodelling and overgrowth after conservative treatment for femoral and tibial
      shaft fractures in children.
AB  - One thousand nine hundred and eighty-four children who had received conservative
      treatment for shaft (diaphyseal and metadiaphyseal) fractures of lower limbs
      (1162 femoral, 822 tibial fractures) at an average age of 8.5 years (range 0-14
      years) were reviewed by clinical and radiographic investigations at an average
      follow-up of 6.6 years (1-15 years). Particularly, two main features were
      evaluated: remodelling of (angular and rotational) deformities and post-traumatic
      overgrowth. Mechanisms underlying these processes are discussed, based on a
      review of the literature, and parameters conditioning their evolution are
      analysed. Finally, criteria for an acceptable reduction (and limits for residual
      deformities that may be tolerated) at the time of conservative treatment are
      proposed.

PMID- 18320369
TI  - Free fibula flap for humerus segmental reconstruction: report on 13 cases.
AB  - In the period between 1994 and 2004, 13 patients (10 male, 3 female) presenting
      with post-traumatic defects to the humerus were treated with vascularised fibula
      graft. Age ranged from 21 to 62 (mean 37) years. Length of the bony defect ranged
      from 6 to 16 cm. Graft fixation was performed with plates in 12 cases, and in one
      case only screws were used. All patients were clinically reviewed between 120
      days and 14 months after surgery. In one patient the flap was lost and a second
      free fibula flap was performed to achieve the reconstructive goal. Mean time for
      segmental bony union was 6 months (range from 3 to 13 months). Vascularised
      fibula graft allows for a successful humerus reconstruction when traditional
      techniques provide unsatisfactory results.

PMID- 18320370
TI  - A new osteosynthesis device for the treatment of proximal humerus fractures.
      Description of the technique and preliminary results.
AB  - The treatment of third proximal humerus complex fractures represents a challenge
      and osteosynthesis techniques are still controversial. The Authors report a new
      device that has been planned and used to treat this type of fracture, suitable
      for both young and elderly patients. The device consists of a perforated
      prismatic-triangular titanium cage (PTTC), available in different sizes so that
      it can be inserted in the bone cavity as a bridge. Thus, it supports the cephalic
      cap and, resting on the metaepiphyseal walls, allows greater and lesser
      tuberosities to be restored using osteosutures or minimal osteosynthesis devices.
      Furthermore, bone chips or bone substitutes can be inserted as filling in the
      perforated parts. From June 2005 to February 2006 we used this osteosynthesis
      surgical technique to treat 10 patients, 4 females and 6 males, all affected by
      proximal humerus complex fractures. No specific complications during and after
      surgery were noticed. The reported results are still to be considered as
      preliminary, but they are very encouraging. In all the cases the effective
      internal stabilisation allowed anatomical reduction of fragments, their stable
      fixation, reconstruction close to standard anatomy and early rehabilitation.

PMID- 18320371
TI  - No effect of forearm band and extensor strengthening exercises for the treatment
      of tennis elbow: a prospective randomised study.
AB  - The objective of this prospective randomised study was to analyse the effect of
      the forearm support band and of strengthening exercises for the treatment of
      tennis elbow. Twenty-nine patients with 30 tennis elbows were randomised into 3
      groups of treatment: (I) forearm support band, (II) strengthening exercises and
      (III) both methods. The patients had a standardised examination at their first
      visit, and then after 6 weeks, 3 months and 1 year. At the latest follow-up,
      there was a significant improvement of the symptoms compared to before treatment
      (p<0.0001), considering all patients independently of the methods of treatment.
      However, no differences in the scores were found between the 3 groups of
      treatment (p=0.27), indicating that no beneficial influence was found either for
      the strengthening exercises or for the forearm support band. Improvement seems to
      occur with time, independent of the method of treatment used.

PMID- 18320372
TI  - Preoperative autologous blood donation in primary total knee arthroplasty:
      critical review of current indications.
AB  - Preoperative autologous blood donation (PABD) is a well established transfusion
      practice in elective orthopaedic surgery, involving immunologic and infective
      advantages but also involving exposure to not negligible risks, and costs as
      well. The aim of this study was to assess the real need for blood transfusions in
      primary total knee arthroplasty (TKA). Between January 2000 and July 2005, 214
      patients underwent primary unilateral TKA. Altogether, 416 autologous blood units
      were collected, however only 47 (11.3%) were transfused. Thirty-eight patients
      (17.8%) received autologous blood, while 4 of them (10.5%) also received
      allogeneic blood. Based on the results of this study, PABD should be recommended
      in well selected patients undergoing TKA: older female patients with a low basal
      haemoglobin level.

PMID- 18320373
TI  - MRI of the knee after locked unreamed intramedullary nailing of tibia.
AB  - We analysed the reason for knee pain after intramedullary (IM) nailing with
      standard MRI sequences at a mean of 27 months (range 2-45) after nail removal in
      eleven patients with a mean age of 30 years (range 15-52). Knee pain was assessed
      in four grades. All our patients had signal changes of fluid in the nail channel,
      areas of low signal intensity in Hoffa's fat pad and subcutaneous low signal
      nodes in front of a thickened patellar ligament. Ten patients had low signal
      adhesions from the nail insertion towards the patellar ligament. Six patients had
      severe knee pain and even marked adhesions. Two patients had no knee pain; one of
      these two had minimal adhesions and the other one no adhesions. Five of the
      patients had a meniscal tear and/or local cartilage reduction. The degree of
      adhesions from the nail insertion in the tibia towards the patellar ligament was
      proportional to the degree of knee pain. No sign of acute inflammation was found.

PMID- 18320374
TI  - Spontaneous bilateral patellar tendon rupture: a case report and review of the
      literature.
AB  - Bilateral rupture of the patellar tendon is a very rare injury. It occurs in
      association with chronic systemic diseases or corticosteroid medications. We
      report a case of a 13-year-old child with Ehlers-Danlos syndrome presenting a
      bilateral patellar tendon disruption of proximal insertion that occurred with a
      trivial trauma. Surgical management consisting in tendon repair with a suture
      anchor technique protected temporarily with a cerclage wiring gives a good
      outcome.

PMID- 18320375
TI  - The use of pre-contoured plates in the treatment of C2-C3 fractures of the distal
      humerus: clinical experience.
AB  - Open reduction and internal fixation is the treatment of choice in distal humerus
      fractures. The aims of the treatment are to obtain anatomic reconstruction and
      restoration of the elbow's geometry followed by stable internal fixation that
      allows immediate rehabilitation. The plates are pre-contoured to fit the natural
      anatomy of the elbow and in the case of complex fractures they provide a guide
      for the anatomic restoration of the distal humerus. The two plates are placed
      parallel with the screws locked together by interdigitation creating a fixed
      angle in the distal fragments that provides stability to the entire distal
      humerus. Using this method we obtained good results according to the Mayo Elbow
      Performance Score (MEPS) and we are able to reduce the incidence of
      complications. Our experience shows also that it can be useful to obtain an
      anatomical reduction of distal humeral fractures using the pre-contoured plates
      in a parallel position recovering the anatomical antiversion of the articular
      surface.

PMID- 18320376
TI  - Surgical treatment of proximal ulna nonunion.
AB  - We reviewed our experience in the surgical treatment of 12 cases of proximal ulna
      nonunion. The primary injuries were 2 fracture-dislocations of the olecranon, 6
      Monteggia lesions and 3 isolated fractures of the proximal ulna. According to the
      type of primary injury and its anatomical site, the nonunions were classified
      into 2 groups, considering that the nonunions nearest to the humerus-ulna joint
      present a more disabling clinical profile and are more difficult to treat: group
      A (6 patients - nonunion within 5 cm from the olecranon tip of the olecranon) and
      group B (6 patients - nonunion between 5 and 10 cm from the olecranon tip of the
      olecranon). In all cases, after fibrous callus debridement and bone surface
      remodelling, fixation was performed with plate and screws and homoplastic
      cortical bone graft (orthogonal or parallel to the plate) and an intercalary bone
      cylinder when the bone defect was severe. In 3 patients (group A), where the
      defect was smaller than 1 cm, fixation of the ulna was combined with a resection
      of the radial neck. Clinical-radiographic healing was achieved in all patients
      followed for a mean of 27 months. Complications included a case of nonunion due
      to failure of the intercalary graft with plate breakage. The patient healed after
      a new surgery performed with same technique. The score, according to the Broberg
      Morrey scoring system, was 78 in group A patients and 93 in group B patients. The
      use of homoplastic cortical bone graft represents an effective technique to
      improve the mechanical properties of the fixation and supports biological union,
      even when the bone defect is severe.

PMID- 18320377
TI  - Management of the subscapularis contracture during shoulder arthroplasty for
      primary glenohumeral arthritis.
AB  - AIM: To evaluate the safety and effectiveness of a particular subscapularis
      release in shoulder arthroplasty for primary glenohumeral arthritis. MATERIALS
      AND METHODS: Twenty-eight patients (19F, 9M) underwent shoulder arthroplasty for
      primary glenohumeral arthritis. Preoperative average Constant Score (CS) was 31.2
      points (range 14-52), active anterior elevation (AAE) 92 degrees (30-100 degrees
      ) and active external rotation (AER) 11 degrees (-40 to 20 degrees ). During
      arthroplasty for subscapularis contracture, patients underwent subscapularis
      release freeing the superior tubular tendon (STT) with a section of the
      coracohumeral ligament (CHL) and the superior glenohumeral ligament (SGHL) and a
      deep release consisting of a section of the middle glenohumeral ligament (MGHL),
      very close to the glenoid labrum, and the inferior glenohumeral ligament (IGHL).
      An anatomic study was performed on 13 cadavers, verifying the structure of
      subscapularis tendon and its relationship with the capsule, the surrounding
      ligaments and the axillary nerve. Moreover, after having placed traction sutures
      on the subscapularis tendon, its lengthening was measured after STT release alone
      and after STT and deep release. The complete absence of neurological and vascular
      lesions was also verified. RESULTS: Average follow-up: 2.9 years. Postoperative
      mean CS was 70.5 (p[Symbol: see text]0.005), with an absolute gain of 39.1. AAE
      increased from 92 degrees to 142 degrees (p=0.001) while AER increased from 8
      degrees to 48 degrees (p=0.002). At the last follow-up, 19 patients (67.8%) were
      very satisfied, 5 patients (17.8%) were satisfied, 3 patients (10.7%) partially
      satisfied and 1 patient (3.5%) unsatisfied. In the anatomic control, the average
      lengthening of subscapularis tendon was 0.9 cm after STT release alone and 2.5 cm
      after STT and deep release. No vascular and neurological lesions were observed.
      CONCLUSIONS: The subscapularis release during shoulder arthroplasty is extremely
      important to obtain the proper balance between anterior and posterior soft
      tissues and to achieve an optimal range of motion and joint stability. An
      adequate anatomical dissection could give good tendon mobilisation and
      lengthening, necessary for a good repair, and lead to a recovery of the range of
      motion, particularly for external rotation.

PMID- 18320378
TI  - Posterior shoulder pain and anterior instability: a preliminary clinical study.
AB  - Different clinical tests have been suggested in the literature as significant
      indicators of anterior shoulder instability. Sometimes patients with recurrent
      anterior shoulder instability may show some muscular guarding thus making the
      evaluation of specific clinical tests very difficult. These patients may also
      report a medical history with posterior shoulder pain that can be also elicited
      during some clinical manoeuvres. From September 2005 to September 2006 we
      prospectively studied patients who underwent an arthroscopic anterior
      capsuloplasty. Shoulder clinical examination was performed including anterior
      shoulder instability tests (drawer, apprehension and relocation tests).
      Furthermore the exam was focused on the presence of scapular dyskinesia and
      posterior shoulder pain. The patients were also evaluated with ASES, Rowe, SST
      (Simple Shoulder Test), Constant and UCLA (University of California at Los
      Angeles) scoring system preoperatively and at the latest follow-up time. In the
      period of this study we observed 16 patients treated for anterior gleno-humeral
      arthroscopic stabilisation, who preoperatively complained also of a posterior
      scapular pain. The pain was referred at the level of lower trapezium and upper
      rhomboids tendon insertion on the medial border of the scapula. It was also
      reproducible upon local palpation by the examiner. Four of these patients also
      referred pain in the region of the insertion of the infraspinatus and teres
      minor. After arthroscopic stabilisation the shoulder was immobilised in a sling
      with the arm in the neutral rotation for a period of 4 weeks. A single physician
      supervised shoulder rehabilitation. After a mean time of 6.8 months of follow-up,
      all the shoulder scores were significantly improved and, moreover, at the same
      time the patients referred the disappearance of the posterior pain. Posterior
      scapular shoulder pain seems to be another complaint and sign that can be found
      in patients affected by anterior shoulder instability. It can also be related to
      eccentric work of posterior stabilising muscles of scapula during the altered
      biomechanics observed in case of anterior shoulder instability. This pain
      responds positively to surgical intervention showing that re-centring the humeral
      head probably also re-establishes the periscapular muscle-firing pattern with a
      mechanism mediated by the proprioceptive system.

PMID- 18320379
TI  - A new test of resistance in the diagnosis of postero-superior rotator cuff tears.
AB  - The aim of this study was to assess the diagnostic accuracy of a new clinical
      test for the diagnosis of subacromial impingement and full thickness postero
      superior rotator cuff tears. One hundred and twenty patients who underwent
      arthroscopic treatment for acromioplasty or cuff repair were previously submitted
      to a new test of resistance. The test is performed in the standing position with
      the involved arm in 90 degrees abduction, 20 degrees -30 degrees anteposition and
      in external rotation (as for full-can test). Thus, the patient was invited to
      follow the way of a spiral drawn on a drawing sheet for 20 turns; 1 turn = from
      the centre to the end of the spiral and vice versa (spiral width = 20 cm). The
      test was considered positive when the patient was not able to conclude it due to
      strength decrease or to shoulder pain. Sensitivity, specificity, positive and
      negative predictive values as well as diagnostic accuracy were calculated for our
      test of resistance. The test resulted scarcely reliable as detector of
      subacromial impingement and not very reliable as detector of small tear. When the
      test is positive there is a high probability that a subacromial disease exists;
      instead, when it is negative there is a high probability that the patient has not
      a large or massive cuff tear. The resistance test (Gum-Turn test) adds to our
      armamentarium of physical examination signs in patients with painful shoulder and
      furnishes further information on possible dimensions of tendinous tear.

PMID- 18320380
TI  - New perspectives in rotator cuff tendon regeneration: review of tissue engineered
      therapies.
AB  - Tissue engineering may play a major role in the treatment of rotator cuff tendon
      lesions through replacement of an injured tendon segment. Tendons have very poor
      spontaneous regenerative capabilities, and despite intensive remodelling,
      complete regeneration is never achieved and the strength of tendon and ligaments
      remains as much as 30% lower than normal even months or years following an acute
      injury. Tendons seem to be the least complex of the connective tissues with
      respect to their composition and architecture and this leads to the expectation
      that they would be more amenable to tissue engineered approaches than other
      tissues. An accurate literature revision was done in order to know the state of
      the art of tissue engineering therapies in the field of rotator cuff
      regeneration. The following techniques of tissue engineering were considered:
      local injection of stem cells or growth factors, gene transfer, in situ tissue
      engineering and in vitro production of bioengineered tendons to be further
      transplanted in the lesion site. So far, few experimental or clinical studies
      have been done on tendon tissue engineering compared to the extensive work on
      other tissues of orthopaedic interest, such as bone and cartilage. The existing
      studies are related to the following tissue engineering methodologies: gene
      transfer, in situ tissue engineering and in vitro production of bioengineered
      tendons. In our opinion the previously described literature revision showed the
      necessity for future studies in this area also because of recent advances in
      biological and bioactive scaffolds.

PMID- 18320381
TI  - Subacromial space in adult patients with thoracic hyperkyphosis and in healthy
      volunteers.
AB  - The assumption that subacromial space decreases in patients with thoracic
      hyperkyphosis arises from sporadic and personal observations. The purpose of this
      study was to compare width of subacromial space calculated on radiographs and CT
      scans of a high number of patients with thoracic hyperkyphosis that registered on
      exams of healthy volunteers. We measured the subacromial space, using Petersson's
      method, on radiographs of 47 patients with idiopathic or acquired thoracic
      hyperkyphosis and of 175 healthy shoulder volunteers. Both groups were further
      distinguished considering gender and age. Females with hyperkyphosis were also
      divided in two subgroups: those with a kyphotic curve of less (24 patients) or
      more (19 patients) than 50 degrees , respectively. Subacromial space of all
      patients and of 21 volunteers was also evaluated using CT. Acromio-humeral space
      was less wide in patients with hyperkyphosis with respect to coeval volunteers of
      the same gender; in females and in subjects older than 60. Subacromial width of
      females with hyperkyphosis whose curve was more than 50 degrees was significantly
      narrower (p<0.05) than that measured on radiograms or CT scans of females with a
      less severe spinal deformity. Decrease of subacromial space may be attributed to
      less posterior tilting of the scapula and to dyskinesis of the scapular movement.
      Scapular malposition causes an anomalous orientation of the acromion that may
      contribute to subacromial impingement. Patients with thoracic hyperkyphosis
      greater than 50 degrees had a subacromial space narrower than that measured in
      patients with a less severe kyphosis. This suggests that subacromial width is
      directly related to severity of thoracic kyphosis. Because hyperkyphosis of
      patients with osteoporotic vertebral fractures may worsen over the time,
      subacromial decompression could give only temporary shoulder pain relief.

PMID- 18320382
TI  - Plates with angular stability: our personal experience in surgical treatment of
      fractures of the proximal extremity of the humerus.
AB  - We here report our experience in the use of locking proximal humerus plates that,
      compared to the old-generation ones, have shown a reduced incidence of
      complications, more manageability and higher preservation of soft tissues. Thirty
      two patients underwent surgical treatment with plates with angular stability: 20
      women and 12 men, with an average age of 52 years; in 6 cases they were fractures
      with 2 fragments, in 20 cases they were with 3 fragments and in 6 cases with 4
      fragments. Results, evaluated according to the Constant Score, with a minimum
      follow-up of 6 months and the longest of 2 years, have revealed a 79-point
      Constant Score one year after surgery (min 42, max 94). In 2 cases we have
      observed necrosis of the epiphysis while there have not been any cases of
      secondary mobilisation of the synthesis equipment. Our findings, if we consider
      the low necrosis percentage, show the good adaptability and the preservation of
      the soft tissues as guaranteed by the synthesis equipment and by the surgery
      performed.

PMID- 18320383
TI  - Informed consent in shoulder surgery.
AB  - Informed consent is an essential tool for diagnosis and therapy in medicine, and
      is of fundamental importance in surgery, where it underpins the operation itself.
      Its origins can be traced back to US forensic medicine but is now incorporated
      into the Italian legal system, with different consequences depending on the
      context in which it is applied. This article describes our experiences in
      shoulder surgery, with suitable references to legislation and analysis of the
      literature studies in this area.

PMID- 18320384
TI  - Efficacy of anatomical prostheses in primary glenohumeral osteoarthritis.
AB  - More than 32.8% of the over-60s suffer from shoulder osteoarthritis. For advanced
      osteoarthritis, arthroplasty is the treatment of choice. Current systems have
      moved on from the first shoulder prosthesis implanted by Neer in 1974, thanks to
      the use of adaptable modular systems. The aim of this study was to investigate
      the effectiveness of anatomical shoulder replacements in 30 cases of primary
      glenohumeral osteoarthritis through clinical and radiographic follow-up for a
      mean of 5 years. All implants were total cemented prostheses. Preoperative
      investigations included a clinical examination, conventional X-rays and CT. The
      Constant-Murley scale was used to evaluate the results; the mean score increased
      from 21.4 preoperative to 69.8 postoperative (p<0.05). In patients aged under 50,
      the increase in the mean postoperative Constant Score and ROM was greater than
      for the sample as a whole. The following complications were encountered: 2
      postoperative radial nerve paralyses, resolving in 3 months, 2 cases of glenoid
      loosening, 1 periprosthetic fracture and 3 cases of pain and stiffness. The
      results led us to conclude that anatomical prostheses are effective in the
      treatment of severe primary glenohumeral arthropathy.

PMID- 18320385
TI  - Medial reconstruction technique in the treatment of complex fractures of humeral
      proximal epiphysis with SMR prosthetic modular system.
AB  - Prosthetic treatment of complex fractures of humeral proximal meta-epiphysis is a
      very complex surgery that often does not lead to satisfactory results. Indeed,
      although in the last 35 years since Neer's studies some progress has been made in
      the knowledge of the anatomy of humeral meta-epiphysis proximal portion, surgical
      technique and prosthetic design, in the literature we find non-homogeneous
      experiences regarding the clinical-functional results. At the same time, such
      experiences agree as far as pain relief is concerned. We report our experience in
      the treatment of complex fractures of humeral proximal epiphysis with SMR (Lima
      Lto, San Daniele, Italy) prosthetic system, using our surgical technique of
      anatomical reconstruction, starting from the medial neck. The case histories, 35
      patients, 30 women and 5 men, aged between 56 and 79, were reported in the
      observation period between April 2000 and February 2005. In 20 cases the right
      shoulder was treated and in 15 the left one. At the follow-up the patients were
      assessed clinically by the average Constant Score and also by X-rays and CT scan
      in order to measure the prosthesis height, its off-set and retroversion.

PMID- 18320386
TI  - Incidence of risk in shoulder surgery : medical-legal repercussions.
AB  - It is generally recognised that any medical-surgical activity entails the risk of
      failure, placing the physician at risk of malpractice claims. In order to protect
      both the physician and the patient, it is important to identify the risk factors
      relating to the various pathological situations and assess both the incidence and
      significance of such risks. Hence, a "Potential Failure Rating" could be devised
      already during the preliminary stages for every type of medical process. Such a
      rating would be useful both in clinical and medicolegal settings. This article
      considers the most common and important risk factors involved in typical diseases
      of the shoulder, from which a relative failure rating is formulated.

PMID- 18320388
TI  - Teaching physician-patient e-mail communication skills in a residency program.

PMID- 18320389
TI  - "I could never just take blood pressures all day long like you do in family
      medicine".

PMID- 18320390
TI  - Family medicine resident confidence with screening for, and communicating about,
      genomic susceptibility to breast cancer.

PMID- 18320391
TI  - Assembling patient-centered medical homes-the Clerkship Initiative.

PMID- 18320392
TI  - Simulation enhances resident confidence in critical care and procedural skills.
AB  - BACKGROUND: The goal of this study was to determine if clinical simulation
      improved resident confidence in performing critical care skills, neonatal
      resuscitation, and colonoscopy. METHODS: Residents participated in clinical
      simulations utilizing high-fidelity medical simulators in a realistic
      environment. We compared resident responses on pre- and post-experience surveys.
      RESULTS: Residents reported satisfaction with quality of demonstrations and
      opportunity for hands-on learning and practice. Residents felt more confident in
      their ability to apply these skills independently and in the applied context.
      CONCLUSIONS: Simulation is a well-accepted teaching method for critical care and
      procedural skills and improves resident confidence.

PMID- 18320393
TI  - Mama Doc.

PMID- 18320394
TI  - Body worlds.

PMID- 18320395
TI  - Six-year update on the financial status of US Family Medicine Departments.
AB  - BACKGROUND: The financial climate for academic family medicine departments is
      increasingly threatened by reductions in federal funding and ever more
      competitive health care markets. OBJECTIVES: Our objective was to evaluate the
      financial status of US Departments of Family Medicine, comparing 1998 and 2004
      data. METHODS: In 1999 and 2005, family medicine department chairs were surveyed
      for the Association of Departments of Family Medicine. Information reported about
      departments' financial status for 1998 and 2004 included department size, faculty
      compensation, revenue sources, expenditures, residents' salary support, payer
      mix, and department reserves. The 2005 survey data were compared to the 1999
      survey reports. RESULTS: Eighty-five departments responded to the 2005 survey
      (69% of 124 departments). For 2004, the largest source of department revenue was
      clinical income; the median percent of revenue from clinical work increased from
      32% in 1998 to 46% in 2004. The contributions of school/government support and
      hospital support decreased. Median expenditures for faculty salaries and fringe
      benefits increased (from 49% to 54%). Although the percentage of departments with
      reserves had increased (from 57% to 71%), 18% of departments reported debt in
      2004. CONCLUSIONS: Family medicine departments increasingly rely on clinical
      income. They continue to be vulnerable to changes in support from government and
      hospital sources, since these sources constitute significant portions of
      department budgets but have declined in the past 6 years.

PMID- 18320396
TI  - Patient perceptions of how physicians communicate during prostate cancer
      screening discussions: a comparison of residents and faculty.
AB  - BACKGROUND: Residents are required to demonstrate competency in communication
      skills. Prostate cancer screening discussions are examples of complex physician
      patient communication processes, requiring an objective presentation of the known
      risks, potential benefits, and scientific uncertainties surrounding screening.
      National organizations recommend shared decision making (SDM) in these
      discussions. METHODS: A stratified analysis to contrast resident and faculty
      outcomes was planned as part of a randomized controlled trial comparing decision
      aids for prostate cancer screening in a suburban Washington, DC, residency
      practice. All eligible men between the ages of 50 and 70 years scheduled for a
      wellness examination with either a resident or a faculty physician were randomly
      assigned to one of two intervention arms (Web- or paper-based decision aid) or to
      the control group (no pre-visit education). Patients were asked to complete exit
      surveys that evaluated their perceptions of key elements of SDM for prostate
      cancer screening (PCS). RESULTS: Patients seen by resident physicians were
      younger than patients seen by faculty, and a smaller proportion had undergone
      previous prostate-specific antigen (PSA) testing. Patients seen by residents and
      faculty reported similar levels of the elements of SDM (eg, knowledge about PCS,
      achieving their desired locus of control for the decision) and similar time spent
      discussing screening. Both groups also had nearly identical decisional conflict
      scores and PSA testing rates. Residents discussed more PCS topics (6.3 versus 5.3
      topics), including more topics that might influence a patient to decide against
      screening, than did faculty physicians. CONCLUSIONS: According to patient
      perceptions, residents appeared to perform as well as faculty in SDM and other
      aspects of PCS discussions, although the topics that they covered with patients
      might have differed.

PMID- 18320397
TI  - Beliefs, motivations, and opinions about moderate drinking: a cross-sectional
      survey.
AB  - BACKGROUND: The relationship of moderate alcohol use and health remains
      controversial and uncertain. How physicians and patients react to this
      uncertainty is unknown. METHODS: We surveyed outpatients at a single urban
      medical center that provides primary and tertiary care. Participants completed a
      self-administered anonymous survey regarding their medical history, usual alcohol
      consumption, and preferences and opinions regarding moderate drinking, defined as
      a drink every 1 to 2 days. All English-speaking individuals ages 21 years and
      older were eligible. RESULTS: A total of 878 outpatients participated, with a
      response rate of 79%. The median age was 47 years, and 57% were women.
      Approximately 60% of drinkers and 35% of abstainers agreed with the statement
      that moderate drinking is a healthy activity and that it is safe for most people.
      About one third of participants cited possible health benefits as part of their
      motivation for drinking alcohol. Those who cited health benefits tended to be
      older, consumed alcohol more frequently but with a lower quantity per drinking
      day, and were more likely to have a history of coronary heart disease. Only about
      10% of participants identified breast cancer as a possible risk of moderate
      drinking. When asked whether they would be willing to consume one drink every 1-
      2 days if their doctor so recommended, 41% of abstainers and 72% of all drinkers
      were willing to do so. CONCLUSIONS: A substantial number of medical outpatients
      cite health benefits as a motivation for drinking alcohol and a willingness to
      drink alcohol regularly if so recommended by a physician, although few recognize
      health risks from drinking alcohol.

PMID- 18320398
TI  - Training and application of community-oriented primary care (COPC) through family
      medicine in Catalonia, Spain.
AB  - The community-oriented primary care (COPC) approach, implemented in various
      countries by family physicians, general practitioners, and other primary care
      workers, integrates clinical medicine with aspects of public health. A process of
      20 years of training health professionals (40-hour workshop) by the professional
      association of family physicians (Catalan Society of Family and Community
      Medicine), training family medicine residents and giving support to health teams
      in Catalonia, Spain, generated a present group of 30 primary care teams involved
      in community health projects. This paper describes and analyzes factors related
      to changes in the health system, the role of family medicine in Spain, and to
      features of the COPC approach and its training methods as elements that narrow
      the gap between training and practice.

PMID- 18320399
TI  - Crossed paths.

PMID- 18320400
TI  - Benefits of comprehensive reproductive health education in family medicine
      residency.
AB  - Given the high prevalence of unintended pregnancy and early pregnancy failure,
      family physicians frequently encounter these clinical problems. Early abortion
      care and miscarriage management are within the scope of family medicine, yet few
      family medicine residency programs' curricula routinely include training in these
      skills. Comprehensive reproductive health education for family physicians could
      benefit patients by improving access to safe care for unintended pregnancy and
      early pregnancy loss and by improving continuity of care, especially for rural
      and low-income women. By promoting reflection on conflicts between personal
      beliefs and responsibility to patients, training in options counseling and
      abortion care fosters patient-centered care and informed decision making.
      Managing pregnancy loss and termination also improves skills in patient-centered
      counseling and primary care gynecology. Multiple studies document the feasibility
      and success of several training models for abortion and miscarriage management in
      family medicine. Incorporating comprehensive reproductive health care into family
      medicine residency training enables family physicians to provide a full range of
      reproductive health services.

PMID- 18320411
TI  - Oral health and oral treatment needs in patients fulfilling the DSM-IV criteria
      for dental phobia: Possible influence on the outcome of cognitive behavioral
      therapy.
AB  - OBJECTIVE: To describe oral health and oral treatment needs in a group of dental
      phobic patients (DSM-IV) and to explore possible relationships between these
      factors and changes in self-reported dental anxiety before and after phobia
      treatment. MATERIAL AND METHODS: Forty patients (25 women) fulfilling the DSM-IV
      criteria for specific phobia were included in the study. Mean age of the group
      was 34.9 years (range 19-60) and mean dental avoidance was 11.2 years (range 3-30
      years). They were treated with cognitive behavioral therapy (CBT) during either
      one session (3 h) or five sessions (1 h each). Oral health was evaluated by
      orthopantomogram and clinical examination. The outcome of the CBT was measured by
      the change in dental anxiety scores (DAS, DFS) and in positive and negative
      thoughts during a standardized dental behavior test from pretreatment to 1-year
      follow-up. RESULTS: Mean (SD) DMFT was 16.5 (5.8), range 3-26; DT was 6.6 (4.2).
      Mean number of teeth with dental treatment need (restorative, periodontal,
      extractions, etc.) was 9.6 (6.9), range 1-28. There were statistically
      significant correlations between number of decayed teeth and decrease in negative
      thoughts (r=-0.39, p=0.048) and maximum anxiety (r=-0.65, p=0.001). The total
      number of teeth with treatment need correlated with an increase in positive
      thoughts (r=0.60, p=0.001) and decrease in maximum anxiety (r=0.50, p=0.015).
      CONCLUSIONS: There are large variations in oral health and treatment needs among
      patients fulfilling the DSM-IV criteria for dental phobia. Patients with the best
      dental health and lowest treatment needs experience the largest increase in
      positive cognitions during exposure to dental treatment at 1-year follow-up.

PMID- 18320412
TI  - Impacts of dental pain on daily activities of adolescents aged 14-15 years and
      their families.
AB  - OBJECTIVE: To assess the prevalence and severity of dental pain on the daily
      lives of adolescents and their families in Brazil, and, in terms of socio
      economic status, whether there are differences in the prevalence of impacts.
      MATERIAL AND METHODS: In a cross-sectional survey of a random sample of 14 to 15
      year-olds in Brazil, the prevalence and severity of dental pain, and how dental
      pain affects daily functioning, were assessed using a child-related
      questionnaire. A family-related questionnaire included questions on a child pain
      inventory and the pain-related impacts on the daily lives of the child's family
      members. RESULTS: 14.5% of children reported high impact levels on their daily
      lives related to dental pain, the more so among girls than among boys, i.e. 16.7%
      compared to 11.6%. Significantly more impacts occurred in lower socio-economic
      class children than in higher, i.e. 19.7% versus 7.8%. The prevalence of impacts
      among children who reported dental pain (n=354) was high; 64.7% reporting that
      concentration at school was affected, 55.6% that home activities were affected,
      and 51.4% that leisure activities were affected. There was a significant
      relationship between impacts of dental pain on children and families. Overall
      prevalence of impacts on children's families was 15.2%. The most frequent family
      dimensions affected were: in carrying out normal household activities (19.7%) and
      in visiting friends and relatives (17.7%). Emotional stability was the most
      frequent psychological activity dimension affected (14.1%); 9.6% of parents were
      woken up as a result of their child's dental pain on an average of 3.7 nights per
      week. CONCLUSIONS: Dental pain has considerable impact on the daily lives of
      adolescents and their families in Brazil. There are many more dental pain-related
      impacts in girls and in lower social class children.

PMID- 18320413
TI  - Effect of dental material fluorescence on DIAGNOdent readings.
AB  - OBJECTIVE: Diagnosis of secondary caries with the DIAGNOdent device has been
      found to be comparable to visual and radiographic diagnostic methods, but the
      fluorescence of restorative materials might affect DIAGNOdent values and result
      in false-positive diagnosis. The aims of this study were: (1) to measure baseline
      fluorescence of restorative materials and fluorescence changes induced by aging,
      bleaching, staining, and polishing; (2) to assess intra-examiner reproducibility
      of these measurements; and (3) to compare the values obtained with the DIAGNOdent
      against the threshold values for enamel and dentinal caries. MATERIAL AND
      METHODS: 270 disk-shaped specimens fabricated from 15 different restorative
      materials were divided into 3 groups, which were aged in water, bleached with 10%
      carbamide peroxide, and stained with red wine. Specimen fluorescence was measured
      with the DIAGNOdent before and after these treatments. The red-wine-stained
      specimens were also polished and measured again. RESULTS: Intra-examiner
      reproducibility of the measurements was excellent. For all materials, baseline
      DIAGNOdent values, as well as the values of aged and bleached samples, were
      considerably lower than the dentinal caries threshold. The values of one stained
      filled resin fissure sealant, one stained resin composite, and one stained resin
      modified glass ionomer exceeded the dentinal caries threshold. Polishing reduced
      these DIAGNOdent values to below the dentinal caries threshold, except for the
      filled resin fissure sealant specimen. CONCLUSIONS: Stained dental materials
      might affect DIAGNOdent readings and consequently result in false-positive
      diagnoses of secondary caries. Dental fillings should be polished prior to
      DIAGNOdent measurement.

PMID- 18320414
TI  - Experimental tooth pain elevates substance P and matrix metalloproteinase-8
      levels in human gingival crevice fluid.
AB  - OBJECTIVE: Tooth pain can induce a neurogenic inflammatory reaction in gingiva in
      association with local elevations of matrix metalloproteinase (MMP)-8, which is
      considered the major tissue destructive protease in gingival crevice fluid (GCF).
      The pro-inflammatory neuropeptides released by sensory nerves coordinate the
      activities of the immuno-effector cells and may influence the secretion of MMP-8.
      With this background, we studied whether experimental tooth pain can trigger
      changes in GCF levels of the neuropeptide substance P (SP) and MMP-8. MATERIAL
      AND METHODS: The GCF SP levels of stimulated and non-stimulated teeth were
      analyzed for SP using a competitive enzyme immunoassay (EIA). The GCF MMP-8
      levels were determined by quantitative immunofluorometric assay (IFMA). RESULTS:
      Painful stimulation of the upper central incisor caused significant elevations in
      GCF SP and MMP-8 levels of the stimulated tooth. At the same time, the GCF SP and
      MMP-8 levels of non-stimulated control teeth were unchanged. CONCLUSIONS: These
      data indicate that experimental tooth pain can induce local elevations of SP and
      MMP-8 levels in GCF simultaneously. This supports the possibility of a local
      neurogenic spread of inflammatory reactions from intrapulpal to surrounding
      periodontal tissues.

PMID- 18320415
TI  - Masseter muscle thickness and mechanical advantage in relation to vertical
      craniofacial morphology in children.
AB  - OBJECTIVE: To investigate the relationship between vertical craniofacial
      morphology and masseter muscle thickness and mechanical advantage in children.
      MATERIAL AND METHODS: The sample comprised 72 children (36 F, 36 M), 8.5-9.5
      years of age, with various malocclusions and no previous orthodontic treatment.
      The thickness of the masseter was measured bilaterally by means of
      ultrasonography, and the recordings were performed both in relaxation and under
      contraction. Mechanical advantage was measured on the lateral cephalograms as the
      ratio between the masseter moment and the bite force moment arms. Two linear
      ratios and three angular measurements were used to describe vertical craniofacial
      morphology. RESULTS: The mean masseter thickness was greater in the male group
      (p<0.05) in both relaxed and contracted conditions. There were no significant sex
      differences for the mechanical advantage or for the measurements of vertical
      craniofacial morphology. In females, there is a positive association between
      masseter muscle thickness and its mechanical advantage. Multiple regression
      analysis showed a positive association between posterior to anterior facial
      height ratio in both genders and a negative association between masseter
      thickness and the intermaxillary angle in females. CONCLUSIONS: There is a
      significant association between posterior to anterior facial height and the
      masseter muscle in children. The importance of the masseter muscle is more
      evident in the vertical facial morphology of females.

PMID- 18320416
TI  - Effects of bFGF on suppression of collagen type I accumulation and scar tissue
      formation during wound healing after mucoperiosteal denudation of rat palate.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of basic
      fibroblast growth factor (bFGF) on collagen changes after mucoperiosteal
      denudation of rat palate. MATERIAL AND METHODS: A total of 36 male Wistar rats
      were divided into control, scar, sham, and bFGF groups. In the scar, sham, and
      bFGF groups, lateral palatal mucoperiosteum was excised to form scar tissue on
      the palate. In the bFGF group, bFGF solution was injected into the operated area
      1 week postoperatively. At 6 weeks postoperatively, the distribution of collagen
      type I and the 3-dimensional structure of collagen fibers were investigated under
      immunofluorescent and scanning electron microscopy. RESULT: In the bFGF group,
      weakly immunostained submucosa was clearly distinguishable from the strongly
      immunostained cervical periodontal ligament and gingiva. Collagen fibers running
      from submucosal tissue into the surface of underlying palatal bone comprised
      loosely arranged collagen fibrils. Lumen structures in collagen fibers resembled
      those in the control group. CONCLUSION: Administration of bFGF for suppression of
      collagen type I generation could suppress scar tissue formation and reduce
      connective strength with adjacent teeth and palatal bone.

PMID- 18320417
TI  - Depth of cure and surface microhardness of experimental short fiber-reinforced
      composite.
AB  - OBJECTIVES: The aim of this study was to analyze the depth of cure of a short
      fiber-reinforced composite (FRC) assessed by microhardness at different curing
      times and storage conditions. MATERIAL AND METHODS: Experimental composite resin
      (FC) was prepared by high-speed mixing 22.5 wt% short E-glass fibers (3 mm in
      length) and 22.5 wt% resin matrix and gradually adding 55 wt% silane-treated
      silica filler. Half-split cylindrical test specimens were produced from both the
      FC and from the conventional particulate composite resin (control, Z250, 3M
      ESPE). The test specimens (n=3/group) were polymerized at different exposure
      times (20, 40, 60 s) and then water-stored at 37 degrees C for 24 h and 30 days
      before testing. A universal testing machine was used for testing Vickers
      microhardness. All results were statistically analyzed with analysis of variance
      (ANOVA). RESULTS: ANOVA revealed that curing time had a significant effect
      (p<0.05) on the microhardness of both composite resins. Depth of cure of
      conventional composite resin (control) was significantly greater than that of FC
      (p<0.05). Microhardness after water storage decreased as curing time increased.
      CONCLUSIONS: The use of short fiber fillers in interpenetrating polymer network
      matrix (IPN) achieved the acceptable depth of cure and microhardness values
      recommended for clinical use, although lower than for commercial composite resin.

PMID- 18320418
TI  - In vitro effect of light-emitting diode light polymerization on the color
      stability of three resin-based restorative materials.
AB  - OBJECTIVE: To investigate the color stability of resin-based restorative
      materials when polymerized with light-emitting diode (LED) curing light in the
      constant or exponential mode. MATERIAL AND METHODS: Eight specimens of Admira
      (AD), Compoglass F (CO), and Tetric EvoCeram (TE) constantly cured or
      exponentially cured with a high-powered LED curing light for 10, 20, or 60 s. The
      CIE-Lab values (L*, a*, b*) were measured prior to and after performing the water
      storage or color stability test according to EN ISO 7491 (Suntest). RESULTS:
      Statistical analysis showed significant changes in the color values after each of
      the aging processes, as well as between DeltaL, Deltaa, Deltab, and DeltaE of the
      materials, which were dependent on curing time, mode, and aging condition
      (p<0.05). CO performed very well during water storage, but AD and TE exceeded the
      clinically relevant limit DeltaE=1. After the Suntest and 180 d additional water
      storage, TE showed the highest mean (SD) DeltaE=4.4 (1.1) to 5.4 (1.9). Although
      AD and CO performed best in the constant mode, they exceeded DeltaE=1. All
      materials shifted to more red. CONCLUSIONS: The extent of discoloration depended
      on (a) the curing mode, (b) the curing time, and (c) the aging condition. Not all
      materials performed clinically acceptably in all tests; TE even showed
      unacceptable DeltaE>3.3. The optimal curing time was 20 s for both curing modes
      and all tested materials.

PMID- 18320419
TI  - Differences in four reported symptoms related to temporomandibular disorders in a
      cohort of 50-year-old subjects followed up after 10 years.
AB  - OBJECTIVE: To assess possible changes in the prevalence of four temporomandibular
      disorder (TMD) symptoms reported by subjects at age 50 and again 10 years later.
      MATERIAL AND METHODS: Identical questionnaires were sent out in 1992 and in 2002
      to all subjects born in 1942 and living in two Swedish counties. Of those who
      answered the four questions on TMD symptoms in 1992, 74% responded in 2002
      (n=4639). The response alternatives were dichotomized into two groups: 1) No
      problems and 2) some, rather severe and severe problems. RESULTS: The mean
      prevalence of TMD-related symptoms reflected small and mainly non-significant
      changes, whereas the prevalence of reported bruxism was significantly greater at
      age 60 than at age 50. Among those with no TMD symptoms at age 50, 5-7% of the
      men and 8-9% of the women reported symptoms at age 60. Of those reporting one or
      more TMD symptoms at age 50, 47-65% of the men and 40-48% of the women had no
      symptoms 10 years later. There was a significant and markedly increased risk of
      reporting TMD symptoms and bruxism (OR>10) at age 60 among those who had symptoms
      at age 50. CONCLUSIONS: The mean prevalence of reported TMD symptoms was
      relatively consistent from age 50 to age 60. The group reporting symptoms at the
      first examination were highly likely still to have the symptoms 10 years later.
      However, approximately half of the subjects with TMD symptoms at age 50 reported
      no symptoms at age 60.

PMID- 18320420
TI  - Prevalence and distribution of demarcated opacities in permanent 1st molars and
      incisors in 6 to 8-year-old Danish children.
AB  - OBJECTIVE: To estimate the prevalence and describe the distribution of demarcated
      opacities and possible consequences of this condition in permanent 1st molars and
      incisors in Danish children. MATERIAL AND METHODS: Among all 6 to 8-year-old
      children in two municipalities, 745 (83.6%) were clinically examined for the
      occurrence of creamy-white or yellowish-brown demarcated opacities, posteruptive
      breakdown of tooth substance in relation to the opacities, atypical restorations,
      and extractions, i.e. restorations or extractions as a result of the occurrence
      of demarcated opacities. RESULTS: In 647 children with four fully erupted
      permanent 1st molars, the prevalence of demarcated opacities and of lesions with
      loss of tooth substance due to demarcated opacities in any 1st molar was 37.3%
      (95% confidence interval (95% CI) 33.6-41.0%) and 6.3% (95% CI 4.7-8.5%),
      respectively. Permanent incisors were 2.5 times more frequently affected among
      children with one or more affected permanent 1st molar than among children with
      no such teeth. Demarcated creamy-white opacities were the type of lesion found
      most frequently, and the most frequently affected tooth types were the upper
      central incisors followed by 1st molars. CONCLUSIONS: Nearly half of the examined
      6 to 8-year-old children had permanent 1st molars or incisors with demarcated
      opacities. More than 6% of the children had macroscopic loss of tooth substance
      due to demarcated opacities.

PMID- 18320422
TI  - Another special issue: 40 years Craig-Gordon model of isotope fractionation of
      water.

PMID- 18320423
TI  - Selected papers of the international workshop on the isotope. Effects in
      evaporation (IWIEE) - revisiting the Craig-Gordon model four decades after its
      elaboration - May 3 to 5, 2006, Pisa, Italy. Preface.

PMID- 18320424
TI  - The isotopic composition of evaporating waters - review of the historical
      evolution leading up to the Craig-Gordon model.
AB  - Attempts to explain the variations in the abundance of heavy isotopic species of
      water throughout the hydrologic cycle solely by means of the classical
      equilibrium-fractionation processes could not be reconciled with measured
      abundances of the isotopic species in residues of "evaporation systems". Focusing
      on the evaporation of surface waters, the paper follows the evolution of the
      concepts during the 1950-ties and early 1960-ties leading up to the formulation
      of the Craig-Gordan Evaporation Model in 1965.

PMID- 18320425
TI  - Revisiting the boundary layer structure used in Craig and Gordon's model of
      isotope fractionation in evaporation.
AB  - Craig and Gordon's (CG) model of isotope fractionation in evaporation was derived
      more than 40 years ago and was based on the turbulent boundary layer structure
      model acceptable at that time. That view suggested that turbulent flows consist
      of eddies with a wide range of length scales moving randomly in the flow domain.
      There is evidence that some parameters in CG model do not fully correspond to
      data in the literature. Owing to advances in fluid dynamics research techniques,
      it has been shown in recent decades that the apparent chaotic flow in turbulent
      boundary layers is in fact governed by few well-organised structures. This
      article reviews the major characteristics of these coherent structures based on
      available results from experimental, numerical and theoretical studies of
      turbulent and laminar boundary layers. The review points on some differences
      between past and present views of the boundary layer structure and on their
      relation and possible influence on power laws in CG model.

PMID- 18320426
TI  - Isotope effects in the evaporation of water: a status report of the Craig-Gordon
      model.
AB  - The Craig-Gordon model (C-G model) [H. Craig, L.I. Gordon. Deuterium and oxygen
      18 variations in the ocean and the marine atmosphere. In Stable Isotopes in
      Oceanographic Studies and Paleotemperatures, E. Tongiorgi (Ed.), pp. 9-130,
      Laboratorio di Geologia Nucleare, Pisa (1965).] has been synonymous with the
      isotope effects associated with the evaporation of water from surface waters,
      soils, and vegetations, which in turn constitutes a critical component of the
      global water cycle. On the occasion of the four decades of its successful
      applications to isotope geochemistry and hydrology, an attempt is made to: (a)
      examine its physical background within the framework of modern evaporation
      models, (b) evaluate our current knowledge of the environmental parameters of the
      C-G model, and (c) comment on a general strategy for the use of these parameters
      in field applications. Despite its simplistic representation of evaporation
      processes at the water-air interface, the C-G model appears to be adequate to
      provide the isotopic composition of the evaporation flux. This is largely due to
      its nature for representing isotopic compositions (a ratio of two fluxes of
      different isotopic water molecules) under the same environmental conditions.
      Among many environmental parameters that are included in the C-G model, accurate
      description and calculations are still problematic of the kinetic isotope effects
      that occur in a diffusion-dominated thin layer of air next to the water-air
      interface. In field applications, it is of importance to accurately evaluate
      several environmental parameters, particularly the relative humidity and isotopic
      compositions of the 'free-atmosphere', for a system under investigation over a
      given time-scale of interest (e.g., hourly to daily to seasonally). With a
      growing interest in the studies of water cycles of different spatial and temporal
      scales, including paleoclimate and water resource studies, the importance and
      utility of the C-G model is also likely to grow in the future.

PMID- 18320427
TI  - Isotope effects accompanying evaporation of water from leaky containers.
AB  - Laboratory experiments aimed at quantifying isotope effects associated with
      partial evaporation of water from leaky containers have been performed under
      three different settings: (i) evaporation into dry atmosphere, performed in a
      dynamic mode, (ii) evaporation into dry atmosphere, performed in a static mode,
      and (iii) evaporation into free laboratory atmosphere. The results demonstrate
      that evaporative enrichment of water stored in leaky containers can be properly
      described in the framework of the Craig-Gordon evaporation model. The key
      parameter controlling the degree of isotope enrichment is the remaining fraction
      of water in the leaking containers. Other factors such as temperature, relative
      humidity, or extent of kinetic fractionation play only minor roles. Satisfactory
      agreement between observed and predicted isotope enrichments for both (18)O and
      (2)H in experiments for the case of evaporation into dry atmosphere could be
      obtained only when molecular diffusivity ratios of isotope water molecules as
      suggested recently by Cappa et al. [J. Geophys. Res., 108, 4525-4535, (2003).]
      were adopted. However, the observed and modelled isotope enrichments for (2)H and
      (18)O could be reconciled also for the ratios of molecular diffusivities obtained
      by Merlivat [J. Chem. Phys., 69, 2864-2871 (1978).], if non-negligible transport
      resistance in the viscous liquid sub-layer adjacent to the evaporating surface is
      considered. The evaporation experiments revealed that the loss of mass of water
      stored in leaky containers in the order of 1%, will lead to an increase of the
      heavy isotope content in this water by ca. 0.35 and 1.1 per thousand, for delta
      (18)O and delta (2)H, respectively.

PMID- 18320428
TI  - Deuterium excess in precipitation of Alpine regions - moisture recycling.
AB  - The paper evaluates long-term seasonal variations of the deuterium excess (d
      excess = delta(2)H - 8. delta(18)O) in precipitation of stations located north
      and south of the main ridge of the Austrian Alps. It demonstrates that sub-cloud
      evaporation during precipitation and continental moisture recycling are local,
      respectively, regional processes controlling these variations. In general, sub
      cloud evaporation decreases and moisture recycling increases the d-excess.
      Therefore, evaluation of d-excess variations in terms of moisture recycling, the
      main aim of this paper, includes determination of the effect of sub-cloud
      evaporation. Since sub-cloud evaporation is governed by saturation deficit and
      distance between cloud base and the ground, its effect on the d-excess is
      expected to be lower at mountain than at lowland/valley stations. To determine
      quantitatively this difference, we examined long-term seasonal d-excess
      variations measured at three selected mountain and adjoining valley stations. The
      altitude differences between mountain and valley stations ranged from 470 to 1665
      m. Adapting the 'falling water drop' model by Stewart [J. Geophys. Res., 80(9),
      1133-1146 (1975).], we estimated that the long-term average of sub-cloud
      evaporation at the selected mountain stations (altitudes between about 1600 and
      2250 m.a.s.l.) is less than 1 % of the precipitation and causes a decrease of the
      d-excess of less than 2 per thousand. For the selected valley stations, the
      corresponding evaporated fraction is at maximum 7 % and the difference in d
      excess ranges up to 8 per thousand. The estimated d-excess differences have been
      used to correct the measured long-term d-excess values at the selected stations.
      Finally, the corresponding fraction of water vapour has been estimated that
      recycled by evaporation of surface water including soil water from the ground.
      For the two mountain stations Patscherkofel and Feuerkogel, which are located
      north of the main ridge of the Alps, the maximum seasonal change of the corrected
      d-excess (July/August) has been estimated to be between 5 and 6 per thousand, and
      the corresponding recycled fraction between 2.5-3 % of the local precipitation.
      It has been found that the estimated recycled fractions are in good agreement
      with values derived from other approaches.

PMID- 18320429
TI  - Mbaka lakes isotopic ((18)O and (2)H) and water balances: discussion on the used
      atmospheric moisture compositions.
AB  - The water balances of small crater lakes Masoko, Katubwi, Kyambangunguru, Ilamba,
      Kingiri, located north of lake Malawi (Tanzania), are established with the Craig
      Gordon model of evaporation. In this approach, it is difficult to evaluate the
      isotopic composition of evaporated vapour (deltaE), which is indirectly estimated
      from the atmospheric moisture signature (deltaA). Given that 'precipitation
      equilibrium' approach does not lead to realistic solutions in this tropical
      region, the lake balances are established and discussed from both the sampled
      deltaA and those derived from the terminal lake Rukwa. The mean local sampled
      signature (deltaAm : delta(18)O =-13.7per thousand and delta(2)H =-76per
      thousand) is inferior to that derived from lake Rukwa (deltaAtl : delta(18)O =
      10.4per thousand and delta(2)H =-64per thousand), which may be due to altitudinal
      and latitudinal effects but both are influenced by recycling continental vapour.
      Water balances enable us to confirm and quantify high inflows and groundwater
      outflows that account for typologies of Mbaka lakes. The proposed sampling and
      measurement method allows us then to access reasonable moisture compositions in
      far-away regions.

PMID- 18320430
TI  - Evaporative isotope enrichment as a constraint on reach water balance along a
      dryland river.
AB  - Deuterium and oxygen-18 enrichment in river water during its transit across
      dryland region is found to occur systematically along evaporation lines with
      slopes of close to 4 in (2)H-(18)O space, largely consistent with trends
      predicted by the Craig-Gordon model for an open-water dominated evaporating
      system. This, in combination with reach balance assessments and derived runoff
      ratios, strongly suggests that the enrichment signal and its variability in the
      Barwon-Darling river, Southeastern Australia is acquired during the process of
      evaporation from the river channel itself, as enhanced by the presence of
      abundant weirs, dams and other storages, rather than reflecting inherited
      enrichment signals from soil water evaporation in the watershed. Using a steady
      state isotope mass balance analysis based on monthly (18)O and (2)H, we use the
      isotopic evolution of river water to re-construct a perspective of net exchange
      between the river and its contributing area along eight reaches of the river
      during a drought period from July 2002 to December 2003, including the duration
      of a minor flow event. The resulting scenario, which uses a combination of
      climatological averages and available real-time meteorological data, should be
      viewed as a preliminary test of the application rather than as a definitive
      inventory of reach water balance. As expected for a flood-driven dryland system,
      considerable temporal variability in exchange is predicted. While requiring
      additional real-time isotopic data for operational use, the method demonstrates
      potential as a non-invasive tool for detecting and quantifying water diversions,
      one that can be easily incorporated within existing water quality monitoring
      activities.

PMID- 18320431
TI  - Estimation of lake water - groundwater interactions in meromictic mining lakes by
      modelling isotope signatures of lake water.
AB  - A method is presented to assess lake water-groundwater interactions by modelling
      isotope signatures of lake water using meteorological parameters and field data.
      The modelling of delta(18)O and deltaD variations offers information about the
      groundwater influx into a meromictic Lusatian mining lake. Therefore, a water
      balance model is combined with an isotope water balance model to estimate
      analogies between simulated and measured isotope signatures within the lake water
      body. The model is operated with different evaporation rates to predict
      delta(18)O and deltaD values in a lake that is only controlled by weather
      conditions with neither groundwater inflow nor outflow. Comparisons between
      modelled and measured isotope values show whether the lake is fed by the
      groundwater or not. Furthermore, our investigations show that an adaptation of
      the Craig and Gordon model [H. Craig, L.I. Gordon. Deuterium and oxygen-18
      variations in the ocean and the marine atmosphere. In Stable Isotopes in
      Oceanographic Studies and Paleotemperature, Spoleto, E. Tongiorgi (Ed.), pp. 9
      130, Consiglio Nazionale delle Ricerche, Laboratorio di Geologia Nucleare, Pisa
      (1965).] to specific conditions in temperate regions seems necessary.

PMID- 18320432
TI  - Delta(18)O characteristics of lichens and their effects on evaporative processes
      of the subjacent soil.
AB  - The study presents first data on the delta(18)O performance of poikilohydrous
      lichen ground cover, and its potential impact on the isotopic composition of
      water fluxes arising from subjacent soil layers. As a model organism, the
      globally distributed lichen Cladina arbuscula was studied under laboratory
      conditions as well as in the field. During a desiccation experiment, delta(18)O
      of the lichen's thallus water and of its respired CO(2) became enriched by
      approximately 7 per thousand and followed a similar enrichment pattern to that
      expected from homoiohydrous, vascular plants. However, the observed degree of
      enrichment was lower in comparison to vascular plants due to (i) the lichen's
      inherent lower evaporative resistances; and (ii) a stronger effect of the more
      depleted surrounding water vapour. In lichens growing in their natural habitat,
      this specific pattern may show substantial variations depending on prevailing
      microclimatic conditions. Within a field study, thallus water delta(18)O of
      lichens principally proved to become more depleted when close to equilibration
      with the surroundings. It thereby strongly depended on the absorption of
      surrounding water vapour. Moreover, the results indicate that lichen mats
      substantially reduce evaporation rates arising from subjacent soil layers, and
      may alter the isotopic signal of vapour diffusing away from these layers into
      more depleted values.

PMID- 18320433
TI  - Trends in birthweight in the north of England.
AB  - This article describes trends in population birthweight distribution in the north
      of England between 1982 and 2000, and reviews the international literature on
      recent birthweight trends in industrialized populations. Two contrasting trends
      were observed: an increase in low birthweight from 7.0% to 7.7% of all births,
      and an increase in births weighing 3500 g or more, consistent with an increase in
      mean birthweight. The rate of multiple births increased over the study period,
      and multiple births accounted for about half of the increase in low birthweight.
      Multiple births are rising due to increasing maternal age, and the development
      and use of assisted reproductive technologies. Low birthweight increased in both
      multiple and singleton births, due entirely to increased low-birthweight live
      births. There was a substantial reduction in low-birthweight stillbirths. The
      rise in low-birthweight live births is multifactorial, but changes in
      registration practice and increased elective delivery are likely contributory
      factors. The increase in high birthweights is likely to reflect reductions in
      smoking during pregnancy, and increased maternal height and weight. The dramatic
      recent rise in maternal body mass index (BMI) at booking is likely to have a
      substantial impact on birthweight and adverse perinatal outcomes in coming
      decades.

PMID- 18320434
TI  - Assisted conception and the audit culture.
AB  - This paper explores the benefits and burdens of regulation in assisted
      conception, drawing on a series of interviews with practitioners and a range of
      recent writings on the social and political context of audit and bureaucracy. The
      process of regulation brings accountability and new competencies to assisted
      conception professionals, increasing their influence locally and nationally.
      Early career and laboratory staff are able to draw on protocols and standard
      operating procedures to improve their practice and enhance their authority within
      the assisted conception team and the wider institution. However, audit
      intensifies the focus upon paperwork rather than practice. Measures such as
      double witnessing can undermine trust amongst professionals, and this can have
      detrimental effects on performance. Systems such as incident reporting can become
      overloaded with minor problems, and do not necessarily allow sufficient time for
      reflection and feedback regarding the best ways of preventing errors. Performance
      data designed to increase patient choice can undermine it when clinics have to
      limit their treatment options or change practices to try to 'improve' their
      results. In conclusion, feedback and discussion between the regulator and a range
      of staff groups enhances the benefits of regulation and reduces its burdens.

PMID- 18320435
TI  - Oral agents for ovulation induction--clomiphene citrate versus aromatase
      inhibitors.
AB  - The purpose of this review is to compare clomiphene citrate (CC) with aromatase
      inhibitors (AI) as the first-line therapy for WHO Group II (eu-oestrogenic)
      infertility. For the past 45 years CC has been the first-line therapy, as it is a
      simple, cheap treatment, almost devoid of side effects, and yields ovulation in
      73%, pregnancy in 36% and a singleton live birth rate of 25%. The gap between
      ovulation and pregnancy rates has mainly been attributed to its anti-oestrogen
      effects on endometrium. AI block oestrogen production, not oestrogen receptors,
      and would therefore be expected to produce superior conception rates and less
      multiple pregnancies. AI have yet to undergo further large, robust clinical
      trials in order to fulfill this promise as a feasible alternative to CC in this
      role, but some preliminary trials have shown at least equality and some
      superiority.

PMID- 18320436
TI  - A survey of clinicians' views on age and access to IVF and the use of tests of
      ovarian reserve prior to IVF in the United Kingdom.
AB  - A national survey was performed to determine current practice in the UK in terms
      of upper age limits for access to in vitro fertilization (IVF) and the use of
      tests of ovarian reserve. A postal questionnaire was sent to lead clinicians of
      all assisted conception units (ACU) listed on the Human Fertilisation and
      Embryology Authority (HFEA) website. Responses were received from 72 out of 84
      (85.7%) units. One-fifth of all responders indicated that 20% of all women
      seeking IVF were more than 40 years old. There was a wide variation in reported
      upper age limits for access to both NHS- (35 - 50 years) and self-funded (42 - 50
      years) IVF. Tests of ovarian reserve were routinely used to exclude women from
      IVF, but the criteria varied. Few women requested oocyte freezing as a measure
      for preserving fertility.

PMID- 18320437
TI  - Live birth following preimplantation genetic screening for trisomy 21. Should
      aneuploidy screening be offered to all older patients undergoing IVF?
AB  - A 42-year-old female patient with history of secondary infertility was referred
      to our assisted conception unit for in vitro fertilization (IVF). Before her
      referral, she had two cycles of IVF at another centre; the first was unsuccessful
      and, after conceiving at the second attempt, the pregnancy was terminated at 14
      weeks' gestation following a positive nuchal translucency scan and a diagnosis of
      trisomy 21 (Down syndrome) by a chorionic villous biopsy performed in the first
      trimester. The screening tests for trisomy 21 were offered to the patient in view
      of her advanced age. Subsequent karyotyping revealed that both partners had a
      normal chromosomal complement. Following genetic counselling, the couple were
      offered IVF treatment along with preimplantation genetic screening for trisomy
      21. Four of the five embryos were suitable for biopsy, and one blastomere from
      each embryo was analyzed using fluorescent in situ hybridization for chromosome
      21. The analysis revealed that two embryos had trisomy 21, one had monosomy 21,
      and only one embryo was diploid for chromosome 21. The single diploid embryo was
      transferred to the uterus on day 3, and resulted in an uneventful pregnancy and
      delivery of a healthy live-born male.

PMID- 18320438
TI  - Risks associated with cryopreservation: a survey of assisted conception units in
      the UK and Ireland.
AB  - A number of recent, high-profile incidents involving loss or damage to
      cryopreserved material held in IVF units or sperm storage centres have
      highlighted the need for centres to carefully review their cryostorage practice
      and take action. Critical disasters involving lost or damaged patient material,
      although high profile, are still thought to be rare, and there has been concern
      that we should ensure that any response is proportionate to risk. However, as no
      regulators, manufacturers or similar professional disciplines have collected
      information in the long term, our knowledge of the true incidence of such adverse
      events is extremely poor. Recognizing the need for some solid data, the UK
      Association of Clinical Embryologists (ACE) conducted a survey on the subject, at
      its joint meeting with the Association of Irish Clinical Embryologists (ICE)
      (January, 2006). Questions were asked in relation to the risk of: injury to
      personnel; and potential loss of and potential damage to stored material. The
      number of serious and not so serious adverse events/situations relating to both
      staff and sample safety are discussed in detail. The incidence of problems was
      certainly higher than we had imagined; the lack of general training and awareness
      amongst our staff is a serious cause for concern, and appears to leave the
      industry vulnerable. Moreover, the survey highlighted the need for a coordinated
      approach to the collection of more detailed information both prospectively and
      retrospectively. Regulators, manufacturers, allied professional bodies and, more
      importantly, centres should be encouraged to share both recent and historic data
      relating to adverse events, in order that accurate risk assessments can be made
      in future.

PMID- 18320439
TI  - Luteal phase support with GnRH-a improves implantation and pregnancy rates in IVF
      cycles with endometrium of <or=7 mm on day of egg retrieval.
AB  - OBJECTIVE: The objective of this study was to examine the use of gonadotrophin
      releasing hormone agonist (GnRH-a) for luteal phase in a group of patients with
      thin endometrium (<or=7 mm) after IVF treatment. METHODS: One-hundred-and-twenty
      women were eligible for this study. Patients were randomly allocated into two
      groups: group A (n = 60) received triptorelin 0.1 mg on the day of ovum pickup
      (OPU), on the day of embryo transfer (ET) and three days thereafter, and group B
      (n = 60) received placebo. The primary outcomes were implantation and pregnancy
      rates. RESULTS: Although there was no significant difference in the number of
      good quality embryos transferred in both groups, the implantation and pregnancy
      rate were significantly higher in the GnRH-a - treated group compared with
      placebo controls. Furthermore, Estradiol (E(2)), progesterone (P) levels and
      endometrial thickness were significantly more elevated in patients who received
      GnRH-a for luteal phase support. CONCLUSIONS: The administration of GnRH-a at the
      time of OPU significantly improves the implantation and pregnancy rates in
      patients with thin endometrium (<or=7 mm).

PMID- 18320440
TI  - Normal birth from cryopreserved embryos after intracytoplasmic sperm injection of
      frozen semen into vitrified human oocytes.
AB  - OBJECTIVE: To describe the birth achieved from frozen embryos after
      intracytoplasmic sperm injection (ICSI) of donor sperm into vitrified oocytes.
      PATIENT: A 25-year-old woman whose husband was azoospermic undergoing IVF
      therapy. METHODS: Oocytes collected after ovarian stimulation were vitrified,
      thawed, and fertilized by frozen donor sperm. RESULTS: Nineteen oocytes were
      vitrified and all survived after thawing. Thirteen of the 19 oocytes that
      underwent ICSI with donors sperm were successfully fertilized. Twelve embryos
      were cryopreserved again by conventional slow-freezing protocol because of
      uterine bleeding on the day of transfer. Three thawed embryos were transferred,
      and a normal male with an infant karyotype of 46,XY was delivered. CONCLUSION:
      This case report demonstrates effective oocyte cryopreservation by vitrification.

PMID- 18320448
TI  - The future of health professional education: some reflections on possibilities
      and complexities.

PMID- 18320449
TI  - Competence, respect and trust: key features of successful interprofessional nurse
      doctor relationships.
AB  - Professional relationships between doctors and nurses have often been seen as
      problematic, a barrier to effective collaborative practice, yet little is known
      about the intrinsic nature of such relationships in the primary care context.
      This study set out to explore roles of, and relationships between, nurses and
      doctors currently working in New Zealand primary care settings. Using a
      qualitative methodology, data were collected using in-depth interviews with 18
      individual nurses and doctors working in primary care settings in Wellington, New
      Zealand. Doctors' and nurses' perceptions of their own and each others' roles,
      and the perceived relationships between individuals from both disciplinary groups
      were explored, using principles of naturalistic enquiry in a mixed method of
      analysis. The study findings indicate that effective interprofessional
      relationships between individual doctors and nurses can, and often do, exist in
      New Zealand primary care settings, although they are not universal. The
      identification and separation of vocational and business roles, and the
      development of professional identity, form the basis for a theory of trust
      development in nurse-doctor interprofessional relationships in New Zealand
      primary care. Professional identity is related to demonstration of professional
      competence, in turn related to development of mutual interprofessional respect
      and enduring interprofessional trust.

PMID- 18320450
TI  - The Canadian Obesity Network and interprofessional practice: members' views.
AB  - We examined interprofessional (IP) attitudes and relationships within an emergent
      network, the Canadian Obesity Network (CON), using semi-structured individual
      interviews with 13 members of the CON. CON is a newly formed network of obesity
      researchers, health professionals, and other stakeholders whose vision is to
      reduce the mental, physical, and economic burden of obesity on Canadians.
      Analysis of participant contributions led to a "Who?, What?, When?, Where?, Why?,
      and How?" framework of IP practice and obesity. Results indicate that a wide
      range of professionals are ready (who?), the issue is apparent (what?), the
      context is multi-located (where?), the timing is right (when?), and there is
      general consensus that IP practice (how?) is the only way to go to effectively
      tackle the obesity issue (why?). Recommendations and suggestions for future
      studies of IP practice in the context of both networks and obesity are made.

PMID- 18320451
TI  - Emergency medicine services: interprofessional care trends.
AB  - To understand trends in emergency medicine and interprofessional roles in
      delivering this care, we analyzed a 10-year period (1995-2004) by provider,
      patient characteristics, and diagnoses. The focus was on how doctors, physician
      assistants (PAs) and nurse practitioners (NPs) share emergency medicine visits.
      The National Hospital Ambulatory Medical Care Survey of over 1 billion "weighted"
      emergency room visits for 1995 to 2004 was analyzed. The majority of patients
      were female (53.2%); the mean age of all patients was 35.3 years old. By 2004,
      physicians were the provider of record for emergency visits at 92.6%, with PAs at
      5.7% and NPs at 1.7%. Emergency visits increased for all three providers over the
      ten years with PA growth doubling during this same period. Medications were
      prescribed for three-quarters of the visits and were consistent in the mean
      number of prescriptions written across the three prescribers. No significant
      differences emerged when urban and rural settings were compared. Expansion of the
      roles and interprofessional care provided by NPs and PAs include increasing
      acceptance, clarification of legal and regulatory aspects of practice, shared
      roles, team approaches to shortages of fully-trained doctors, and the limitation
      of working hours of physician postgraduate trainees. The US forecast for
      emergency department visits is expected to outpace the growth of the population
      and the supply of emergency medicine providers. In view of an increasing
      emergency medical demand and a continuing shortage of physician personnel,
      policies are needed for workforce planning to meet the demand.

PMID- 18320452
TI  - Skills integration in a simulated and interprofessional environment: an
      innovative undergraduate applied health curriculum.
AB  - The objective of our study was to propose an innovative applied health
      undergraduate curriculum model that uses simulation and interprofessional
      education to facilitate students' integration of both technical and "humanistic"
      core skills. The model incorporates assessment of student readiness for clinical
      education and readiness for professional practice in a collaborative, team-based,
      patient-centred environment. Improving the education of health care professionals
      is a critical contributor to ultimately improving patient care and outcomes. A
      review of the current models in health sciences education reveals a scarcity of
      clinical placements, concerns over students' preparedness for clinical education,
      and profession-specific delivery of health care education which fundamentally
      lacks collaboration and communication amongst professions. These educational
      shortcomings ultimately impact the delivery and efficacy of health care.
      Construct validation of clinical readiness will continue through primary research
      at The Michener Institute for Applied Health Sciences. As the new educational
      model is implemented, its impact will be assessed and documented using specific
      outcomes measurements. Appropriate modifications to the model will be made to
      ensure improvement and further applicability to an undergraduate medical
      curriculum.

PMID- 18320453
TI  - Difficulties in collaboration: a critical incident study of interprofessional
      healthcare teamwork.
AB  - The challenge for members of interprofessional teams is to manage the team
      processes that occur in all teamwork while simultaneously managing their
      individual professional identities. The aim of this study was to identify and
      describe difficulties perceived by health professionals in interprofessional
      teamwork. Utterances on verbal actions and resolutions were also explored to
      enable a discussion of the implications for interprofessional learning.
      Individual interviews using a Critical Incident Technique were performed with 18
      Swedish professionals working in healthcare teams, and examined with qualitative
      content analysis. The main findings show difficulties related to the team dynamic
      that arose when team members acted towards one another as representatives of
      their professions, difficulties that occurred when the members' various knowledge
      contributions interacted in the team, and difficulties related to the influence
      of the surrounding organization. The perceived consequences of the difficulties,
      beyond individual consequences, were restrictions on the use of collaborative
      resources to arrive at a holistic view of the patient's problem, and barriers to
      providing patient care and service in the desired manner. This paper also
      discusses how experiences of managing difficulties entailed various forms of
      interprofessional learning situations.

PMID- 18320454
TI  - Interprofessional education in Denmark.

PMID- 18320455
TI  - Using technology to overcome some traditional barriers to effective clinical
      interprofessional learning.

PMID- 18320456
TI  - Bringing down the Berlin Wall in academia.

PMID- 18320464
TI  - Enzymatic preparation of cefaclor with immobilized penicillin acylase.
AB  - Enzymatic syntheses of cefaclor by immobilized penicillin acylase under kinetic
      control were carried out. According to the initial reaction rate ratio of
      synthesis to hydrolysis (Vs/Vh), penicillin acylase from Alcaligenes faecalis was
      chosen as the suitable catalyst for the synthesis of cefaclor. The reaction
      conditions, such as temperature, pH, and substrate concentration were
      investigated based on their Vs/Vh values. In the process of preparing cefaclor,
      in situ product removal (ISPR) and acyl donor feeding were used to achieve high
      yield. At the optimal conditions, the yield of cefaclor was 90%. In addition, the
      product were separated and purified, the total yield of cefaclor was 61%.

PMID- 18320465
TI  - One-step separation of IgG subclasses of DNA hydrolyzing autoantibodies: a study
      on sera of patients with systemic lupus erythematosus and primary
      antiphospholipid syndrome by histidine ligand affinity chromatography.
AB  - A method based on histidine ligand affinity chromatography has been utilized for
      the separation of DNA hydrolyzing autoantibodies from sera of patients suffering
      from systemic lupus erythematosus and primary antiphospholipid syndrome using the
      gel, histidyl-aminohexyl-sepharose. The separation of autoantibodies was carried
      out under mild chromatographic conditions. Human IgG subclass distribution in the
      different fractions separated on the column was studied by enzyme-linked
      immunosorbent assay. The purified DNA hydrolyzing autoantibodies were shown to
      hydrolyze plasmid DNA.

PMID- 18320466
TI  - Rapid purification of annexin V from human placenta by affinity chromatography.
AB  - Affinity purification of annexin V from human placenta on column with appropriate
      monospecific antibodies is developed. The procedure permits purification of the
      protein to a highly purified state by a two stage procedure. The yield of the
      protein is about 5 mg per 100 g of wet tissue. Because of high homologies between
      various annexins, it was supposed that this procedure can be also applied for
      purification of other annexins from other tissues.

PMID- 18320467
TI  - Synthesis of a precursor dipeptide of thymopentin in organic solvents by an
      enzymatic method.
AB  - The protease-catalyzed, kinetically controlled synthesis of a precursor dipeptide
      of thymopentin(TP-5), Z-Arg-Lys-NH2 in organic solvents was studied. Z-Arg-OMe
      was used as the acyl donor and Lys-NH2 was used as the nucleophile. An industrial
      alkaline protease alcalase and trypsin were used to catalyze the synthesis of the
      target dipeptide in water-organic cosolvent systems. The conditions of the
      synthesis reaction were optimized by examining the effects of several factors,
      including organic solvents, water content, temperature, pH, and reaction time on
      the yield of Z-Arg-Lys-NH2. The optimum conditions using alcalase as the catalyst
      are pH 10.0, 35 degrees C, in acetonitrile/DMF/Na2CO3-NaHCO3 buffer system
      (80:10:10, V/V), 6 h, with the dipeptide yield of 71.1%. Compared with alcalase,
      the optimum conditions for trypsin are pH 8.0, 35 degrees C, in ethanol/Tris-HCl
      buffer system (80:20, V/V), 4 h, with the dipeptide yield of 76.1%.

PMID- 18320468
TI  - Purification and structure analysis of antifreeze proteins from Ammopiptanthus
      mongolicus.
AB  - We purified many kinds of antifreeze proteins with high activity from the leaves
      of Ammopiptanthus mongolicus by several biochemical techniques. The antifreeze
      activities of these AFPs were measured by both osmometry and differential
      scanning calorimetry, and the inhibition of growth of ice crystals by the AFPs
      was obvious. Additionally, the antifreeze proteins were analyzed by sequencing,
      glycosylation reaction, mass spectroscopy, and circular dichroism spectroscopy.
      Both samples have some other unique structures different from those of fishes and
      of insects. It was suggested that plant AFPs might have a particular antifreeze
      mechanism in comparison with that of fish and insects.

PMID- 18320469
TI  - Production of extracellular alkaline alpha-amylase by solid state fermentation
      with a newly isolated Bacillus sp.
AB  - Production of alkaline alpha-amylase employing our laboratory isolate, Bacillus
      sp., under solid state fermentation, was optimized. The effect of wheat bran and
      lentil husk was examined. Lentil husk exhibited the highest enzyme production.
      The appropriate incubation time, inoculum size, moisture level, and buffer
      solution level were determined. Maximum yields of 216,000 and 172,800 U/g were
      achieved by employing lentil husk and wheat bran as substrates in 0.1 M
      carbonate/bicarbonate buffer at pH 10.0 with 30% initial moisture level at 24 h.
      Inoculum size and buffer solution level were found to be 20% and 1:0.5 for two
      solid substrates.

PMID- 18320470
TI  - Enhancing ethanol fermentability of an artificial acid hydrolyzate with anion
      exchange resin treatment.
AB  - To assess the effectiveness of anion exchange resins (Dowex M43 and Dowex
      monosphere 66) in neutralization and detoxification of an acid hydrolyzate
      solution, a fermentation medium containing inhibitors was inoculated with
      Saccharomyces cerevisiae. When treated with resins at a 1:1 ratio (vol:wt) for up
      to 20 min, 55-67% of furan and more than 95% of phenolic compounds were removed.
      Ethanol fermentation activity in resin-treated fermentation medium was the same
      as the control. There was 21-43% of the total sugar loss after one resin
      treatment, depending on the sugar concentration. Additional treatments increased
      sugar retention rate to 95%.

PMID- 18320471
TI  - Mechanical stretch induced interleukin-18 (IL-18) expression through Angiotensin
      subtype 1 receptor (AT1R) and endothelin-1 in cardiomyocytes.
AB  - Interleukin-18 (IL-18) is a proinflammatory cytokine with multiple biological
      functions. We and others have demonstrated that an increased level of circulating
      IL-18 is one of the risk factors for cardiovascular diseases. Endothelin-1 (ET-1)
      has been reported to be a potent hypertrophy-promoting factor through RhoA and
      Rho-Kinase. Mechanical stretch induces a hypertrophic response, partly through
      the production of ET-1 through Endothelin A receptor (ETAR). Moreover, it has
      also been reported that mechanical stretch induces cardiac hypertrophy through
      Angiotensin subtype 1 receptor (AT1R). However, the mechanism by which the IL-18
      gene expression is regulated in cardiomyocytes has not yet been fully understood.
      This study was designed to elucidate the functional significance of IL-18 gene
      expression in response to mechanical stretch. Neonatal rat cardiomyocytes
      cultured on silicone dishes were subjected to stretch. The moderate 20%
      mechanical stretch resulted in the elevation of IL-18 expression in a time
      dependent manner with the maximal level achieved 36 hours after the stretch.
      Olmesartan, AT1R antagonist inhibited stretch-induced IL-18 expression. ETAR
      blockade BQ123 inhibited stretch-induced IL-18 expression. However, the
      Endothelin B receptor (ETBR) receptor blockade BQ788 did not inhibit this
      reaction. ET-1 induced IL-18 expression, with a peak induction after 4 hours of
      incubation. These results might suggest that stretch stimulation of
      cardiomyocytes induced ET-1 and, subsequently, ET-1 up-regulated the IL-18
      expression. Furthermore, Fasudil, a Rho-Kinase inhibitor, and Simvastatin, a HMG
      CoA reductase inhibitor, led to a significant reduction in mechanical stretch
      induced IL-18 expression. These results indicated, for the first time, that IL-18
      expression is induced by mechanical stretch in cardiomyocytes via the ETAR, AT1R,
      and the Rho/Rho-K pathways. The induction of IL-18 from cardiomyocytes by
      mechanical stress might cause the deterioration of cardiac functions in autocrine
      and paracrine fashion. The inhibition of IL-18 expression induced by mechanical
      stress might be one of the mechanisms that account for the beneficial
      cardiovascular effects of AT1R antagonist, ETAR blockade, Statin, and Rho-Kinase
      inhibitor.

PMID- 18320473
TI  - Seminars in Ophthalmology, Volume 23-Issue 2, Neuro-Ophthalmology. Introduction.

PMID- 18320474
TI  - Interventional neuroradiology for the ophthalmologist.
AB  - The past two decades have witnessed major advances in diagnosing vascular
      conditions that affect blood supply and hemorrhagic risk to the brain and the
      eye. Technological improvements have resulted in the ability to better
      radiologically image the cerebrovascular system and to deliver pharmacological
      and embolic agents that have high specificity. Neuroradiological interventional
      therapy has become the preferred option in managing many conditions that were
      previously treated by standard neurosurgical procedures. Some of these conditions
      were considered either inoperable or treatable only with unacceptable
      neurosurgical risks. This article reviews the current state of the
      neuroradiological interventional management in conditions that may be encountered
      in ophthalmological practice.

PMID- 18320475
TI  - An update on acquired nystagmus.
AB  - Proper evaluation and treatment of acquired nystagmus requires accurate
      characterization of nystagmus type and visual effects. This review addresses
      important historical and examination features of nystagmus and current concepts
      of pathogenesis and treatment of gaze-evoked nystagmus, nystagmus due to vision
      loss, acquired pendular nystagmus, peripheral and central vestibular nystagmus,
      and periodic alternating nystagmus.

PMID- 18320476
TI  - Giant cell arteritis.
AB  - This review summarizes the diagnosis, clinical manifestations and management of
      giant cell arteritis. Giant cell arteritis is an immune-mediated vasculitis of
      medium to large sized arteries that affects individuals older than the age of 50.
      Patients typically present with signs of vascular insufficiency of the
      extracranial arteries of the head and systemic inflammation. Temporal artery
      biopsy remains the hallmark of diagnosis. Specific treatment regimens must be
      tailored to each individual, but steroids remain the backbone of therapy.

PMID- 18320477
TI  - Inherited thrombophilia and the eye.
AB  - Inherited thrombophilic disorders are a well-recognized risk factor for systemic
      thromboembolism. These disorders include deficiencies of anticoagulant proteins
      such as protein C, protein S, and antithrombin III, abnormalities of factor V and
      prothrombin resulting from genetic mutations, and hyperhomocysteinemia. Except
      for hyperhomocysteinemia, which has been associated with both venous and arterial
      thrombosis, the other heritable disorders primarily cause venous thromboembolism.
      We have reviewed the association between heritable thrombophilia and the
      development of thrombosis in the eye. The available literature consists of case
      control studies and case reports. Preliminary data suggest a relationship between
      thrombotic disorders of the eye and the inherited hypercoagulable states. Some
      reports show a risk of thrombosis with the presence of factor V Leiden and
      hyperhomocysteinemia but these associations frequently disappear upon
      multivariate analysis. It is possible that inherited thrombophilia plays a
      supportive role to well-established risk factors such as hypertension and
      diabetes. Larger, well-designed studies will be necessary to clearly define the
      role of inherited thrombophilia in the development of thrombotic disorders of the
      eye.

PMID- 18320478
TI  - Vision rehabilitation and Charles Bonnet Syndrome.
AB  - PURPOSE: To evaluate the prevalence of visual hallucinations in Charles Bonnet
      Syndrome (CBS) among patients at a Low Vision Clinic. To determine whether Low
      Vision Rehabilitation (LVR) intervention results in a decrease of these visual
      hallucinations. METHODS: We surveyed 50 consecutive new patients in a low vision
      clinic to determine whether they had experienced visual hallucinations consistent
      with CBS. All patients were: questioned about the presence of visual
      hallucinations; given an educational handout that described CBS and reassured
      them of the benign nature of these hallucinations; and administered Folstein's
      Mini Mental Status Examination (MMSE). During their low vision examination, all
      patients received low vision aids to improve their visual function. At follow-up
      patients who had symptoms of CBS were administered a second survey to evaluate
      whether they had experienced any change in the frequency of their visual
      hallucinations. RESULTS: Of the 50 patients surveyed, 12 of 50 (24%) had visual
      hallucinations typical of CBS. 6 of these 12 patients (50%) had daily recurring
      hallucinations. At mean follow-up of 34.9 +/-30 days, a second survey was
      administered to 11 of the 12 patients diagnosed with CBS. One patient was lost to
      follow-up. Three of the 11 patients (27.3%) experienced a decrease in the
      frequency of their hallucinations by 43.33% +/-30.55%. Eight of 11 patients
      (72.7%) did not note a change in their symptoms. CONCLUSIONS: It is important to
      include direct questions regarding visual hallucinations in the case history of a
      low vision examination. LVR may decrease the frequency of CBS hallucinations in
      some patients. Rehabilitation strategies should include low vision devices that
      allow for improved visual function and patient education to provide needed
      reassurance.

PMID- 18320479
TI  - Intracranial hypertension in systemic lupus erythematosus.
AB  - PURPOSE: Intracranial hypertension (IH) mimicking pseudotumor cerebri (i.e.,
      idiopathic IH) has been reported in individuals with systemic lupus erythematosus
      (SLE) since the 1960s. Although various mechanisms have been proposed (e.g.,
      venous thrombosis, medication side effect, and immunologic or inflammatory
      disease) none have been proven to be causal. METHODS: Retrospective chart review
      of patients with IH and SLE at a single tertiary care institution. RESULTS: In a
      cohort of IIH patients the percentage of patients in our study with SLE was 1% (4
      in 410). Three out of the four patients had serologic evidence for a
      hypercoagulable state but only one had cerebral venous sinus thrombosis. Two
      patients had onset or worsening of IH in close temporal relationship to steroid
      withdrawal. The course, treatment, and prognosis of our patients with SLE and
      intracranial hypertension did not differ significantly from our clinical
      experience with IIH or with the published natural history data for IIH.
      CONCLUSIONS: The association of SLE and IH may occur more than by chance alone.
      Steroid withdrawal in the treatment of the SLE may be a predisposing or
      precipitating factor in the development of IH in these patients rather than the
      inflammatory effects of SLE per se. The hypercoagulable state in some patients
      with SLE may also produce cerebral venous sinus thrombosis as an additional
      potential mechanism of IH.

PMID- 18320480
TI  - Endoresection of irradiated choroidal melanoma as a treatment for intractable
      vitreous hemorrhage and secondary blood-induced glaucoma.
AB  - A 50-year-old man presented with uncontrolled erythroclastic glaucoma and
      recurrent vitreous hemorrhage from a previously irradiated choroidal melanoma.
      Despite trabeculectomy, intraocular pressure became uncontrolled due to
      increasing bleeding from the melanoma. The vitreous hemorrhage became voluminous
      and could not be stopped with multiple vitrectomies with endolaser,
      transpupillary thermotherapy, and transscleral laser. Endoresection of the
      regressed tumor and its bleeding vasculature resulted in immediate cessation of
      the bleeding and control of the intraocular pressure.

PMID- 18320481
TI  - [When pregnant women become ill].

PMID- 18320482
TI  - [Medical problems in pregnancy. The viewpoint of gynecologists and
      obstetricians].

PMID- 18320483
TI  - [Antibiotic therapy in pregnancy].
AB  - Apart from pregnancy-related ascending and hematogenous infections, non-pregnancy
      associated may be a potential thread for pregnant women as well as for their
      unborn children. Infections are one of the causes of abortion during the first
      trimester, whereas during second and third trimester, they represent the primary
      cause of preterm birth. Both pregnant women and their physicians may feel
      profoundly uncertain with regards to appropriate treatment. If antimicrobial
      agents are indicated, beta-lactam antibiotics are generally safe and effective.
      With respect to penicillins, an approximately 10 per cent maternal allergy rate
      should be taken into consideration, and first-generation cephalosporins may be a
      suitable alternative. Among the macrolide antibiotics, erythromycin should be
      preferred. Clindamycin, metronidazole, sulfonamides and chloramphenicol may be
      used as second-line agents, however, sulfonamides and chloramphenicol should be
      avoided during the prepartal period. Glycopeptide and aminoglycoside antibiotics
      should be reserved for life-threatening maternal infections refractory to other
      antibiotics. Tetracyclins may only be used before the 12 (th) week of gestation.
      Quinolones should be strictly avoided due to potential toxicity for the unborn
      children.

PMID- 18320484
TI  - [Antibiotic treatment from the obstetrician's point of view].

PMID- 18320485
TI  - [Right iliac vein obstruction (compression by a large tumor mass)].

PMID- 18320486
TI  - [Diagnosis and therapy of venous thrombosis in pregnancy].

PMID- 18320487
TI  - [Deep vein thrombosis in pregnancy: an increase is to be feared].

PMID- 18320488
TI  - [Anemia and thrombocytopenia in pregnancy].

PMID- 18320489
TI  - [Anemia and thrombocytopenia: early detection of risks].

PMID- 18320490
TI  - [Diabetes in pregnancy].

PMID- 18320491
TI  - [Diabetes in pregnancy--still a great challenge].

PMID- 18320493
TI  - [Acute kidney failure: pathophysiology and clinical management].

PMID- 18320494
TI  - [Immunology of tuberculosis and current status of vaccine development].
AB  - Even 125 year after the discovery of Mycobacterium tuberculosis as the
      aetiological agent of tuberculosis by Robert Koch, tuberculosis is still a global
      health emergency according to WHO. The high infection rate with M. tuberculosis
      that persists in the human host until a weakened host immune system allows a
      reactivation and complicated and expensive antituberculous chemotherapy urgently
      demand the development of new vaccines. Increasing numbers of multidrug-resistant
      tuberculosis, especially in the successor states of the former Soviet Union and
      China, further complicate an efficient tuberculosis control. For decades, there
      was no new release of an antituberculous drug to efficiently fight tuberculosis.
      Hence, also drug development has to keep up with the development of resistance by
      the pathogen. The following review describes the immune response to M.
      tuberculosis infection and the deduction of strategies for novel vaccines. Thanks
      to international financial support, several new vaccine candidates are already in
      the pipeline and close to clinical testing phases.

PMID- 18320495
TI  - [Trial end-point in chronic obstructive pulmonary disease (COPD): minimal
      clinically important difference].
AB  - The concept of the minimal clinically important difference (MCID) is intended to
      provide a measure of relevance for a statistically applied in patients with COPD.
      Clinically important differences are those differences relevant to the individual
      patient and important to the patient's life. However, people's difference in a
      diagnostic parameter perception of what is important vary. Furthermore,
      physicians may rate the significance of a particular marker and its difference
      which can be achieved by a pharmacological intervention differently from the
      patient. Thus, the major problem with defining an MCID for any measure is that
      the most important differences, which require the most subtle measures for an
      individual patient, are likely to have the least general application. Conversely,
      measures that can be generalised are unlikely to have much individual importance
      and will be very crude tools for an individual assessment. In medical trials
      both, statistical rigor and clinical relevance are generally required, and MCID
      is without doubt a key application tool defining treatment success or treatment
      failure. This paper gives an update on the concept of a minimal important
      difference of most relevant parameters in COPD treatment.

PMID- 18320496
TI  - [Non-invasive ventilation and physical exercise in patients with COPD].
AB  - The use of non-invasive ventilation (NIV) to improve physical activity in COPD
      patients has been addressed in several clinical investigations in the past. In
      general, NIV can be applied directly during exercise, but also intermittently
      when used for long-term treatment thereby aiming at improving physical activity
      during spontaneous breathing. There is increasing evidence that NIV enhances
      exercise capacity in COPD patients with a reduction of exercise-induced dyspnea
      when applied during exertion. Furthermore, physical training has been shown to
      produce positive results when training was performed under NIV-aided conditions.
      However, the results regarding tolerance of NIV, exercise ability and dyspnea are
      individually different. In most studies where NIV was applied during exercise,
      patients had no indication for long-term NIV, and patients were ventilated with
      low inspiratory pressures, which produced varying results. In contrast, the use
      of higher inspiratory pressures in hypercapnic COPD patients was more effective
      in enhancing exercise capacity. The intermittent application of NIV also
      positively affects exercise capacity in COPD patients, although different results
      were achieved with different ventilator strategies, mainly with a variety of
      inspiratory pressure levels. Different ventilation modes were used for NIV to aid
      exercise and for the intermittent approach in addition to different settings:
      CPAP, pressure support ventilation, proportional assist ventilation and
      controlled NIV. Therefore, it is still unclear how to define the best technique
      for NIV to be used in order to enhance exercise capability in COPD patients.
      Future studies are needed to define which subgroup of patients benefit from NIV
      in view of its effects on exercise. Further studies should also be aimed at
      clarifying which mode and which ventilator settings are most beneficial in
      improving exercise capability in COPD patients.

PMID- 18320497
TI  - [Effects of high altitude on bronchial asthma].
AB  - Sojourns in the high mountains have been recommended to patients with asthma for
      many decades. It is the aim of this contribution to summarise the published
      studies about the effects of a stay at > 1500 m above sea level on asthmatic
      patients. These data from 428 adolescent and adult patients indicate an
      improvement of asthma symptoms and lung function during sojourns at high
      altitude. In many patients a reduction of the steroid therapy was achievable.
      Profound changes in the immune system have been demonstrated at high altitude,
      with a reduction of B- and T-helper cell activation. Total and mite-specific
      immunoglobulin E antibodies decrease significantly during longer sojourns. These
      changes are associated with a reduction of airway inflammation (e. g., reduction
      of eosinophil activation, NO exhalation and bronchial hyper-responsiveness). The
      fact that also patients with non-allergic asthma demonstrate a reduction of their
      airway inflammation at high altitude suggests that the high altitude climate has
      beneficial effects on asthma beyond the effects of allergen avoidance. High UV
      exposure and low humidity could be important additional factors, to explain the
      reductions in asthma severity in the high mountain climate. Larger controlled
      studies should be performed to prove the positive effects of the high altitude
      climate on asthma.

PMID- 18320500
TI  - [Invasive streptococcal infections].
AB  - The severity of streptococcal infections depends upon different virulence of
      individual strains of its causative agent. The most important species are beta
      haemolytic group A streptococci (GAS). Clinical manifestations include skin
      affections, respiratory tract infections and, in particular, serious systemic
      invasive infections. The pathogenicity of GAS is derived from cell wall
      components and extracellular products, especially toxins with properties of the
      so-called superantigens. Less invasive forms of the disease are include
      necrotizing fasciitis, myositis, pneumonia, sepsis without focus, arthritis,
      meningitis, puerperal sepsis, streptococcal toxic shock syndrome (STSS) and
      severe course of erysipelas and cellulitis with blood culture positive for GAS.
      In most cases, soft tissue infections dominate, often accompanied by chronic
      diseases of lower extremities in elderly patients. The other clinical forms are
      rather rare. In children, the condition is clearly frequently related to
      chickenpox. The generally accepted therapeutic management comprises comprehensive
      intensive care, early administration of penicillin in combination with
      clindamycin, and surgical intervention. The use of intravenous immunoglobulins
      (IVIG), elimination methods and hyperbaric oxygen are under discussion. The
      slight increase in cases and ineffective prevention require rapid assessment of
      diagnosis and adequate treatment as a protracted course of the condition is
      connected with a high mortality rate.

PMID- 18320501
TI  - [Cholera--the current state and perspectives of cholera prevention].
AB  - Although more than 40 years have passed since the outbreak of the 7th cholera
      pandemic, the disease continues to be a threat. The Indian subcontinent, Latin
      America and many African countries constantly struggle with the disease that
      still claims thousands of human lives each year. Increasingly, cholera as an
      imported disease is seen in developed countries. The fight against cholera
      infection is predominantly focused on prophylaxis, as antibiotics represent only
      useful additional therapy shortening the duration of the disease and accelerating
      clearance of the bacilli from the organism. Recently, immunogenic components of
      the etiological agent causing cholera have been studied intensely, resulting in
      an effort to construct acellular vaccines. Important immunogenic factors include
      surface lipopolysaccharides of the cholera-causing agent which play a crucial
      role in pathogenesis and manifestation of infection due to the pathogen. Thus,
      these components in particular are pivotal in developing a progressive vaccine
      against cholera.

PMID- 18320502
TI  - [New perspectives of the phage therapy].
AB  - A solution to the problem of the increasing number of antibiotic-resistant
      bacterial strains can be the use of rational phage therapy. In the past,
      bacteriophages (phages) were often used for the treatment and prevention of
      infections and unlike antibiotic therapy, phage therapy caused almost no serious
      side effects. While previously several preparations containing whole phage
      particles were available for phage therapy, currently, the isolation of well
      characterised and purified phage components with antibacterial properties opens
      up new options for the management of intractable infections caused primarily by
      the bacterial genera Enterococcus, Escherichia, Klebsiella, Listeria, Proteus,
      Pseudomonas, Salmonella, Shigella, Staphylococcus and Streptococcus. In addition
      to human and veterinary medicine, the phage therapy principles also find use in
      the agriculture and food industry. Recent and former clinical studies as well as
      numerous animal model experiments have supported that phage therapy is an
      effective and safe alternative of antibiotic treatment of bacterial infections.

PMID- 18320503
TI  - [Pulsed-field gel electrophoresis and its practical use].
AB  - Pulsed-field gel electrophoresis was developed for separating and analyzing of
      long DNA fragments in alternating electric field. In homogenous electric field,
      fragments longer than 50 kb run as a broad, unresolved band with high mobility.
      PFGE separated the DNA by periodicaly changing the direction of electric field.
      DNA molecules are moving "zig-zag" through the gel and they can be better
      separated. Fragments of several megabases can be resolved using this method. PFGE
      can be used for genome mapping of microorganisms as well as higher organisms. In
      microbiology, PFGE is a standard method for typization of bacteria. Comparison of
      electrophoresis profiles after digestion od DNA from bacterial isolates with
      restriction endonuclease is a very useful epidemiologists tool. Genetically
      identical organisms have the same PFGE profiles, different strains have different
      profiles. Related strains have also similar electrophoretic profiles. This
      enables to determine if the outbreaks are caused by the same strain of
      microorganism, to locate the source of outbreak and to monitor the spread of the
      microorganism. The most followed-up are nosocomial and the food-borne pathogens.
      PFGE can be also used for monitoring genetic evolution of the microorganism and
      the most prevalent types which circulate in population. This can be very useful
      for preparation of vaccines.

PMID- 18320504
TI  - [Infectious complications of surgically treated musculoskeletal injuries: review
      of risk factors and etiological agents in years 2000-2005].
AB  - PURPOSE: Infection is considered one of the most serious complications of the
      surgical treatment of musculoskeletal injuries. The aim of the study was to
      evaluate known risk factors and etiological agents of infectious complications in
      patients surgically treated for musculoskeletal injuries within 6 years. METHODS:
      In a group of 5 234 patients followed in 2000-2005 the early or delayed
      infectious complication developed in 65 patients (26 women, 39 men, age 22-83
      years). In every patient with infectious complication the important risk factors
      related to personal history, type of the injury, surgery and other treatment were
      recorded and microbiological culture results were collected. RESULTS: In 60
      patients (92.3%) at least one of the following risk factors was registered:
      diabetes mellitus, age above 75 years, abuse of alcohol and drugs, distant
      infectious focus or severe skin disease at the time of surgery, polytrauma
      requiring long-termed stay in intensive care unit, extensive soft tissue injury
      associated with closed or opened fracture. In 27 patients (41.5%) grampositive
      cocci and in 17 patients (26.2%) gramnegative bacteria were isolated, in 12
      patients (18.5%) mixed bacterial flora was identified and 9 patients (13.8%) had
      negative cultures. The most severe findings from microbiological view occurred in
      patients with extensive soft tissue injury associated with fracture, diabetes or
      long-termed stay in intensive care unit. CONCLUSION: The infectious complications
      after the surgical treatment of musculoskeletal injuries occurred predominantly
      in patients with risk factors. The extensive soft tissue injury associated with
      fracture, diabetes and long-termed stay of the polytrauma patient in intensive
      care unit were identified as the most frequent risk factors. The patients of
      these risk groups also presented with the most serious microbiological findings.

PMID- 18320505
TI  - [Recommendation for diagnostics and therapy of toxoplasmosis in persons with HIV
      infection].
AB  - Reactivation of latent toxoplasmosis is a serious complication in patients with
      deep immunodeficiency, but the disease has a good prognosis if early diagnosed
      and effectively treated. Definitive etiologic proof of the reactivation may be
      difficult and thus an empiric method (therapeutic trial) is used for confirmation
      of the diagnosis in clinical practice. The preferred therapy is a combination of
      pyrimethamine + sulfadiazine.

PMID- 18320506
TI  - Exophthalmometry values of Turkish adult population and the effect of age, sex,
      refractive status, and Hertel base values on Hertel readings.
AB  - PURPOSE: To establish normal exophthalmometry values in the adult Turkish
      population, and the impact of age, gender, interpupillary distance, Hertel base
      selection, and refractive status on globe position. METHODS: Exophthalmometry
      measurements and refractive status of 2477 subjects were conducted in one
      tertiary and five primary health care centers. Change of globe position by age,
      intersex differences in terms of globe position, correlations of Hertel base with
      exophthalmometry results, and interpupillary distance (IPD) were evaluated.
      Multiple linear regression analysis was performed to test determination effect of
      each variable on final Hertel reading. RESULTS: Median Hertel reading was 13 mm,
      and 95% of the population had an upper limit of 17 mm for both eyes. There was a
      negative correlation between spherical equivalent of refractive status and
      exophthalmometry results and a weak positive correlation between IPD and
      exophthalmometry result. Mean Hertel value was found to decrease significantly
      after the third decade. Hertel base value was found to have moderate linear
      correlation with Hertel results. A weak correlation was detected with Hertel
      base/IPD ratio with final Hertel results. Multiple linear regression analysis was
      performed and only 13% and 20% of change in Hertel values bilaterally were found
      to be determined by other variables (age, IPD, refractive status, and Hertel base
      value) for females and males. CONCLUSIONS: Normative dataset for exophthalmometry
      results of the Turkish population is established to be used in clinical practice
      and research. Only 13% to 20% of change in Hertel values was detected to be
      determined by age, IPD and Hertel base values.

PMID- 18320507
TI  - Color Doppler imaging of retrobulbar hemodynamics in Sturge-Weber syndrome
      associated glaucoma.
AB  - PURPOSE: Sturge-Weber syndrome (SWS) is frequently associated with early onset
      glaucoma in the eye on the same side as the facial angioma. The exact cause of
      glaucoma in SWS is poorly understood and difficult to treat. The purpose of this
      study is to investigate the ocular hemodynamics of children with SWS-associated
      glaucoma using color Doppler imaging techniques. METHODS: This is a prospective
      study of 10 pediatric patients with unilateral SWS-associated glaucoma. Color
      Doppler imaging was used to measure the peak systolic velocity and the end
      diastolic velocity of both the ophthalmic and central retinal arteries in the
      glaucomatous eye compared to the fellow healthy eye. RESULTS: Twenty eyes of 10
      children with SWS (6 boys) with unilateral glaucoma were included in the
      prospective study. The mean age of the 10 participants was 5.5 years. When
      compared to their contralateral normal eyes, the glaucomatous eyes had greater
      CDR (p<0.001) and a myopic shift (p=0.04). No significant differences were found
      in the measurements of ocular blood flow velocities of the ophthalmic and central
      retinal arteries. CONCLUSIONS: Vascular pathology has been proposed to play a
      role in SWS glaucoma etiology. The authors did not find arterial retrobulbar
      blood flow differences between the glaucomatous and the fellow normal eye. Since
      the primary vascular anomaly in patients with SWS is in the venous plexus, a
      bigger prospective trial is warranted in order to better understand and treat
      children with SWS glaucoma.

PMID- 18320508
TI  - Effect of pterygium surgery on corneal topography.
AB  - PURPOSE: To evaluate the effect of successful pterygium surgery on corneal
      topography. METHODS: Computerized corneal topography was performed on 20 eyes
      with pterygium before and 3 months after successful excision and limbo
      conjunctival autograft surgery. Corneal shape, corneal spherical power, simulated
      keratometric astigmatism, surface regularity index (SRI), and surface asymmetry
      index (SAI) were assessed before and after surgery. Pre- and postoperative
      uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA),
      and manifest refraction spherical equivalent (MRSE) were also evaluated. RESULTS:
      Changes in corneal shape were mainly a decrease in midline corneal flattening.
      Corneal spherical power was 41.65+/-3.29 diopters (D) (mean +/- SD)
      preoperatively and 44.58+/-1.55 D postoperatively (p=0.04). Simulated
      keratometric astigmatism was 5.47+/-3.45 D preoperatively and 1.79+/-1.52 D
      postoperatively (p=0.0005). SRI was 1.39+/-0.93 preoperatively and 1.10+/-0.57
      postoperatively (p=0.03). SAI was 1.17+/-1.09 preoperatively and 0.75+/-0.73
      postoperatively (p=0.02). UCVA was 0.31+/-0.33 preoperatively and 0.52+/-0.32
      postoperatively (p=0.04). BSCVA was 0.73+/-0.20 preoperatively and 0.89+/-0.16
      postoperatively (p=0.008). MRSE was -0.54+/-3.29 D preoperatively and -1.30+/
      3.05 D postoperatively (p=0.45). CONCLUSIONS: Corneal topographic changes caused
      by the pterygium are almost reversible after surgical treatment. Successful
      pterygium surgery significantly reduces topographic astigmatism, SRI, SAI, and
      corneal flattening. However, precise prediction of these refractive changes is
      not always accurate.

PMID- 18320509
TI  - Evaluation of threshold estimation and learning effect of two perimetric
      strategies, SITA Fast and CLIP, in damaged visual fields.
AB  - PURPOSE: The threshold estimation, learning effect, and between-algorithm
      differences of the Fast Swedish Interactive Thresholding Algorithm (SITA Fast),
      of the Humphrey Field Analyzer (HFA), and the Continuous Light Increment
      Perimetry (CLIP) strategy of the Oculus Twinfield perimeter were evaluated in
      damaged visual fields. METHODS: Twenty-one glaucomatous patients with damaged
      visual fields (MD worse than -8 dB) underwent Oculus Full Threshold (FT),
      Humphrey FT, SITA Fast, and CLIP 30-2 perimetric examinations. All the tests were
      repeated in a second session at least 3 days later. The point-wise differences in
      absolute sensitivity and of the total deviation plot values between FT and fast
      algorithms, between fast algorithms and the learning effect were evaluated
      (Wilcoxon test and Bland-Altman analysis). RESULTS: The average point-wise
      sensitivity difference between SITA Fast and HFA FT strategy (0.84 dB) was
      significantly lower than that found between CLIP and Oculus FT strategy (1.71
      dB). Between-algorithm point-wise differences of the total deviation plot values
      of the fast strategies were not significantly different. Learning effect for SITA
      Fast (0.67 dB) was higher than that found for CLIP (0.39 dB). Test time for SITA
      (367+/-71 sec) and CLIP (453+/-98 sec) were about 55% and 35%, respectively,
      shorter (p<0.001) than those found with FT algorithms. The acceptance for fast
      algorithms and particularly for CLIP was significantly better. CONCLUSIONS: The
      two fast strategies, even though using very different algorithms, showed good
      threshold estimation compared to FT strategies with a consistent time saving in
      damaged visual fields.

PMID- 18320510
TI  - Combined phacoemulsification and Ahmed valve glaucoma drainage implant: a
      retrospective case series.
AB  - PURPOSE: To report on the efficacy and safety of combined phacoemulsification and
      an Ahmed valve glaucoma drainage implant with respect to visual acuity
      improvement, intraocular pressure (IOP) control, and requirement for antiglaucoma
      medication. METHODS: A retrospective chart review was conducted of 41 eyes (31
      patients) with coexisting visually significant cataracts and uncontrolled
      glaucoma who had combined phacoemulsification and Ahmed valve implantation. The
      outcome measures were: visual acuity, IOP, antiglaucoma medication requirements,
      and intra- and post-operative complications. Success was categorized as absolute
      (IOP<21 mmHg without the need for antiglaucoma medication) and relative (IOP<21
      mmHg with one or more antiglaucoma medications). Failure was considered to be an
      IOP<6 mmHg or IOP>21 mmHg on maximally tolerated medications or any devastating
      complication. RESULTS: The mean patient age was 67.3+/-5.9 years old. The mean
      visual acuity improved from 0.73+/-0.5 to 0.16+/-0.16 (p=0.000). The mean IOP
      decreased from 28.2+/-3.1 to 16.8+/-2.1 (p=0.000, 40.4%), while the number of
      antiglaucoma medication decreased from 2.6+/-0.66 to 1.2+/-1.4 (p=0.000). The
      absolute and relative success rates were 56.1% and 31.7%, respectively; 5 eyes
      (12.2%) were considered failures. There were no intraoperative complications;
      postoperative complications occurred in 8 eyes (19.5%). A hypertensive phase was
      detected in 12 (29.3%) eyes. CONCLUSIONS: Combined phacoemulsification and Ahmed
      valve glaucoma drainage implantation is a safe and effective alternative to
      phacotrabeculectomy in patients with coexisting cataract and refractory glaucoma.

PMID- 18320511
TI  - Physician attitudes regarding prostaglandin treatment for glaucoma in the United
      States and Europe.
AB  - PURPOSE: To evaluate physician use of prostaglandins (latanoprost, travoprost,
      and bimatoprost) in the United States (US) and Europe (EU). METHODS: One thousand
      multiple-choice surveys were distributed via e-mail in the US and EU. RESULTS:
      The authors received 71 responses (US 40 [8%] and EU 31 [6%]). Physicians
      preferred prostaglandin monotherapy (US 39 [98%] and EU 22 [71%], p=0.003),
      usually latanoprost (US 32 [80%] and EU 22 [71%], p=0.45). When more efficacy was
      required, US physicians would typically switch (23 [58%]) and EU physicians would
      add therapy (22 [71%], p=0.007). In both continents 45% of respondents stated
      bimatoprost was more efficacious. CONCLUSIONS: US and EU physicians prefer
      prostaglandin monotherapy, most commonly latanoprost. Bimatoprost is often
      perceived as more effective, but having a higher incidence of conjunctival
      hyperemia.

PMID- 18320512
TI  - Rarebit perimetry and frequency doubling technology in patients with ocular
      hypertension.
AB  - PURPOSE: To test the capability of rarebit perimetry (RP), a recent non
      conventional perimetric technique, in detecting early functional damage in
      subjects with ocular hypertension (OHT) and to compare RP findings with those
      obtained by frequency-doubling technology (FDT) perimetry. METHODS: Thirty
      patients with OHT were matched with 30 healthy subjects. All were tested with RP
      and FDT. Frequency-doubling technology mean deviation (MD) and pattern standard
      deviation (PSD), as well as RP mean hit rate (MHR), of the two groups were
      analyzed. The agreement between the two techniques was tested by Kappa analysis.
      RESULTS: In the OHT group the mean (SD) FDT MD was 0.5 (2.1), the mean (SD) FDT
      PSD was 4.2 (1.6), and the mean (SD) RP MHR was 81.4 (6.7). In the control group,
      corresponding values were mean (SD) FDT MD 1.1 (1.4), mean (SD) FDT PSD 3.0
      (0.3), mean (SD) RP MHR 96.2 (2.0). The differences between the two groups were
      not significant for the studied indexes. Eleven (36.6%) out of the 30 OHT eyes
      had abnormal RP results; 12 (40.0%) eyes had abnormal FDT results. Five (16.6%)
      eyes had abnormal RP and FDT findings. Only 1 eye (3.3%) in the control group had
      abnormal RP results and 3 eyes (10.0%) had abnormal FDT results. RP and FDT
      showed a moderate agreement (Kappa=0.43; 95% CI: 0.42 to 0.51). CONCLUSIONS: RP
      and FDT showed VF defects not shown in standard automated perimetry in the OHT
      group. This may be indicative of an increased risk in developing glaucoma, even
      if a gold standard for detecting subtle defects is not currently available. RP
      has the additional advantage of not requiring any expensive device to be used.
      The poor agreement between these techniques in identifying eyes with early damage
      warrants further investigations. Large longitudinal studies are needed before
      defining the role of RP in early glaucoma diagnosis.

PMID- 18320513
TI  - Results of combined phacoemulsification and viscocanalostomy in patients with
      cataract and pseudoexfoliative glaucoma.
AB  - PURPOSE: Coexisting pseudoexfoliation glaucoma (PEXG) and cataract represents a
      special challenge. Although phacotrabeculectomy is an effective procedure, it
      combines the risks of phacoemulsification and trabeculectomy. This study
      evaluates phacoviscocanalostomy to manage eyes with PEXG and cataract. METHODS:
      We conducted a prospective noncomparative study that included 30 consecutive eyes
      of 22 patients with uncontrolled PEXG and cataract. Phacoviscocanalostomy was
      performed in all. Success rate based on postoperative intraocular pressure (IOP)
      reduction and requirement for topical antiglaucoma medication was evaluated as
      the main outcome measure. Visual acuity and complication rates were secondary
      outcomes. RESULTS: The mean follow-up was 18.6 months +/-6.2 (SD) (range 12 to 36
      months). There was statistically significant decrease in mean IOP from 25.3+/-5.2
      mmHg preoperatively to 13.5+/-6.0 mmHg 1 day after surgery (p< .05), 12.3+/-3.1
      mmHg at the final follow-up (p< .05), and at all evaluations to the last
      postoperative visit. Only three eyes (10%) required a single antiglaucoma
      medication to achieve the target IOP. A complete surgical success (IOP <21 mmHg
      without medication) was achieved in 90%, while a qualified success (IOP <21 mmHg
      with or without glaucoma medication) was achieved in 100% of cases. Complications
      included Descemet membrane microperforations (13.3%), macroperforation (3.3%),
      zonular dehiscence (6.6%), and transient postoperative IOP spike (3.3%).
      CONCLUSIONS: Phacoviscocanalostomy achieved excellent IOP control and visual
      acuity improvement in pseudoexfoliation patients with coexisting cataract and
      glaucoma. Complication rate was low and did not affect the surgical outcome.

PMID- 18320514
TI  - Cataract surgery in exudative uveitis: effectiveness of total lens removal,
      anterior vitrectomy, and scleral fixation of PC IOLs.
AB  - PURPOSE: Cataract surgery in exudative uveitis is often followed by severe
      complications (pupillary seclusion/occlusion, dense posterior capsule/anterior
      vitreous opacification, cystoid macular edema following repeat YAG laser
      procedures) which often drastically limit functional recovery. Total removal of
      cataract, anterior vitrectomy, and scleral fixation of a posterior chamber (PC)
      intraocular lens (IOL) has been tried as a surgical alternative, searching for
      lessened postsurgical complications and a better outcome. METHODS: Group A was a
      cohort of 12 patients with cataract after exudative (mostly sarcoidosis and Vogt
      Koyanagi-Harada) uveitis, subjected to intracapsular cataract extraction,
      anterior vitrectomy, and scleral fixation of PC IOLs. Group B was the control
      group, including 12 patients with a similar clinical condition subjected to
      phacoemulsification or extracapsular cataract extraction plus in the- bag or in
      the-sulcus IOL implantation. Follow-up time for both groups was at least 7 years.
      RESULTS: Postoperative inflammatory signs were substantially less in Group A
      patients, from 2 days up to >7 years postsurgery. Group A patients showed no
      cells/exudates adhering to the IOL surfaces, no synechiae, minimal (as compared
      to Group B) vitreous opacifications, and significantly higher visual acuity
      (p=0.024 at the seventh year control). Group A patients reported less frequent
      relapses of uveitis postsurgery, but the relevant clinical data did not allow
      statistical evaluations. CONCLUSIONS: Total removal of cataract in highly
      exudative uveitic eyes, plus anterior vitrectomy and scleral fixation of PC IOLs,
      although technically a more demanding surgical procedure, proved to be safe and
      more effective than classical procedures.

PMID- 18320515
TI  - Association of plasma homocysteine and macular edema in type 2 diabetes mellitus.
AB  - PURPOSE: The aim of this study was to assess the association of macular edema
      (ME) with plasma homocysteine, vitamin B6, vitamin B12, and folic acid levels in
      patients with Type 2 diabetes. METHODS: Sixty-five diabetic subjects with no
      retinopathy and nonproliferative diabetic retinopathy (NPDR) (no DR, without ME,
      with ME: 16, 25, 24, respectively), 28 with proliferative diabetic retinopathy
      (PDR) (with and without ME: 14, 14, respectively), and 19 healthy subjects as
      control were recruited in this cross-sectional study. Plasma homocysteine,
      vitamin B12, vitamin B6, and folate levels were determined after 8-hour of
      fasting for all subjects. The levels of serum homocysteine and vitamin B6 were
      measured using high performance liquid chromatography (HPLC) with fluorescence
      detection, and the levels of serum vitamin B12 and folic acid were measured by
      electrochemiluminescence immunoassay. RESULTS: When diabetic groups with ME were
      compared with diabetic groups without ME for homocysteine, vitamin B12, vitamin
      B6, and folic acid, the only significant difference was detected in homocysteine
      levels (p=0.001). There was no significant difference between NPDR with ME group
      compared with NPDR without ME group and no DR group for plasma homocysteine,
      vitamin B12, vitamin B6, and folic acid (p=0.200, p=0.660; p=0.999, p=0.678;
      p=1.0, p=0.248; p=1.0, p=0.982, respectively). On the other hand, when PDR with
      ME group was compared with PDR without ME group, there was only significant
      difference in homocysteine levels (p=0.023). CONCLUSIONS: Mild to moderate
      elevation of homocysteine may explain the role of vascular dysregulation and
      endothelial dysfunction in patients with DR. The present study suggests
      hyperhomocysteinemia may be one of the crucial risk factors for development of
      ME.

PMID- 18320516
TI  - Atherosclerotic and thrombophilic risk factors in patients with recurrent central
      retinal vein occlusion.
AB  - PURPOSE: Atherosclerotic and thrombophilic risk factors may be causes of central
      retinal vein occlusion (CRVO). The aim of this study was to evaluate the
      prevalence of the aforesaid risk factors in patients with recurrent CRVOs and
      patients with a single episode of CRVO. METHODS: Seventeen patients with
      recurrent CRVO and 30 with a single episode of CRVO were enrolled. The
      atherosclerotic risk factors investigated were hypertension, diabetes, smoking,
      and dyslipidemia. Specific laboratory tests for the following thrombophilic
      markers were performed: homocystinemia (Hcy), lipoprotein (a), factor VIII,
      factor II G20210A and factor V G1691A polymorphisms, lupus anticoagulant,
      anticardiolipin antibodies, plasminogen activator inhibitor-1, and deficit of
      vitamins B6, B12, and folic acid. A multivariate analysis, adjusted for age,
      gender, traditional and thrombophilic risk factors, was performed. Statistical
      significance was set at p<or=0.05. RESULTS: Hypercholesterolemia,
      hypertriglyceridemia, fasting, and postmethionine hyperhomocysteinemia (HHcy)
      were more prevalent in recurrent CRVO patients (p<0.001, p<0.001, p=0.006, and
      p=0.005, respectively). At multivariate analysis, hypercholesterolemia (OR: 5.04,
      95% CI 1.39-18.17; p=0.025), hypertriglyceridemia (OR: 5.60, 95% CI 1.52-20.61;
      p=0.017), fasting HHcy (OR: 5.77, 95% CI 1.39-23.89; p=0.028), and postmethionine
      HHcy (OR: 10.88, 95% CI 2.50-47.42; p=0.002) were found to be significantly
      associated with recurrent CRVO. CONCLUSIONS: Dyslipidemia and
      hyperhomocysteinemia are independent risk factors for the occurrence of recurrent
      CRVO. A complete assessment of atherosclerotic and thrombophilic risk factors in
      CRVO patients. In addition, the need for a specific treatment is suggested.

PMID- 18320517
TI  - Correlation of visual function impairment and OCT findings in patients with
      Stargardt disease and fundus flavimaculatus.
AB  - PURPOSE: To investigate the relationship between morphologic lesions of the
      retina and functional abnormalities in patients with Stargardt disease (STGD) and
      fundus flavimaculatus (FFM). DESIGN. Case-controlled, prospective, comparative
      observational study. METHODS: A complete ophthalmologic examination, including
      best-corrected visual acuity (BCVA) and optical coherence tomography (OCT), was
      performed in 61 eyes of 32 consecutive patients with STGD/FFM and in 60 eyes of
      30 matched healthy control subjects. Furthermore, fundus-related perimetry was
      performed in 12 of the affected eyes. RESULTS: The age ranged from 21 to 71 years
      in STGD/FFM patients and from 21 to 72 years in controls. BCVA ranged from 20/20
      to 20/400 and from 20/20 to 20/32, respectively, in STGD/FFM patients and in
      controls. A foveal thinning was found by OCT Stratus in almost all cases (average
      160 microm) compared with controls (average 210 microm) (p<0.001). BCVA
      impairment significantly correlated to the degree of foveal thinning (r2=0.16;
      p=0.0014). Moreover, in STGD/FFM patients the authors observed two types of
      hyperreflective deposits which were not correlated with BCVA impairment or foveal
      thinning. In addition, fundus-related perimetry revealed a stable fixation in
      8/12 eyes, that was predominantly central in only 4 of these eyes. A smaller
      degree of foveal thinning correlated to a more stable fixation (p=0.0108), even
      if not predominantly central (p=0.0218). CONCLUSIONS: In this series, lower
      visual acuity and unstable fixation correlated with a greater transverse foveal
      thinning. OCT and fundus-related perimetry may be useful tools in STGD/FFM
      patients.

PMID- 18320518
TI  - Retinal photocoagulation for proliferative sickle cell retinopathy: a prospective
      clinical trial with new sea fan classification.
AB  - PURPOSE: To compare the clinical outcome of stage III proliferative sickle cell
      retinopathy (PSR) treated by peripheral retinal scatter photocoagulation to
      natural course disease. METHODS: Long-term follow-up of 101 patients enrolled in
      a prospective trial of photocoagulation for PSR has been completed. Among 202
      eyes of 101 patients enrolled at the University Eye Clinic of Creteil, 73 eyes
      showed a stage III PSR, which the authors further divided into five new grades
      (A, B, C, D, E) considering size, hemorrhage, fibrosis, and visible vessels.
      Grading was based on a three-mirror fundus examination, 360 degrees color
      photographs, and fluorescein angiography. Mean follow- up was 4 years. RESULTS:
      Thirty-eight treated eyes and 35 untreated eyes were included in this study. The
      evolution was not statistically significant between treated and untreated groups
      concerning flat sea fan <1 MPS disc area (grade A) or elevated sea fan with
      partial fibrosis (grade C). Progression and regression were compared between the
      two groups for grade B, resulting statistically significant (p<0.05). Nine
      complications (13%) were observed, which only occurred in untreated patients with
      elevated sea fan and hemorrhage (grade B) or complete fibrosed sea fan with well
      defined vessels (grade E) (p<0.05). CONCLUSIONS: These data suggest that patients
      with grade A or C new sea fan classification should not be initially treated but
      observed.

PMID- 18320519
TI  - Intracameral Avastin dramatically resolves iris neovascularization and reverses
      neovascular glaucoma.
AB  - PURPOSE: To report the biologic effect of intracameral bevacizumab in patients
      with iris neovascularization secondary to proliferative retinal vasculopathies.
      METHODS: Sixteen eyes of 15 patients with iris neovascularization associated with
      or without neovascular glaucoma secondary to proliferative retinal vasculopathies
      received intracameral bevacizumab (1.25 mg). Ophthalmic evaluations included
      Snellen visual acuity (VA), complete ophthalmic iris angiography, and slit lamp
      photography. Main outcome measure was change in degree of iris
      neovascularization. Secondary outcomes included fluorescein iris angiographic
      leakage, control of intraocular pressure, and changes in VA. RESULTS: All
      patients with neovascularization demonstrated by slit lamp photography and
      fluorescein angiography (16/16 eyes) had complete (or at least partial) reduction
      in leakage of the neovascularization within 3 weeks after the injection. Leakage
      from iris neovascularization resolved in 12 of 16 (75%) eyes. In two cases
      recurrent leakage was seen as early as 4 weeks necessitating repeat injection.
      Intraocular pressure was controlled with maximum medical therapy in eight of nine
      eyes reducing the need for glaucoma surgery. Visual acuity improved from a median
      of hand motions to 20/200. CONCLUSIONS: In summary, intracameral bevacizumab was
      effective in reversing iris neovascularization in the majority of patients. It
      also facilitated intraocular pressure control in patients with associated
      glaucoma.

PMID- 18320520
TI  - Bevacizumab-augmented retinal laser photocoagulation in proliferative diabetic
      retinopathy: a randomized double-masked clinical trial.
AB  - PURPOSE: To evaluate the additional therapeutic effect of single intravitreal
      bevacizumab injection on standard laser treatment in the management of
      proliferative diabetic retinopathy. METHODS: A prospective, fellow-eye sham
      controlled clinical trial was conducted on 80 eyes of 40 high-risk characteristic
      proliferative diabetic retinopathy type II diabetics. All cases received standard
      laser treatment according to Early Treatment Diabetic Retinopathy Study protocol.
      Avastin-assigned eyes received 1.25 mg intravitreal bevacizumab (Genentech Inc.,
      San Francisco, CA) on the first session of their laser treatments. Fluorescein
      angiography was performed at baseline and at weeks 6 and 16, and proliferative
      diabetic retinopathy regression was evaluated in a masked fashion. RESULTS: The
      median age was 52 years (range: 39-68) and 30% of the participants were male. All
      patients were followed for 16 weeks. A total of 87.5% of Avastin-injected eyes
      and 25% of sham group showed complete regression at week 6 of follow-up
      (p<0.005). However, at week 16, PDR recurred in a sizable number of the Avastin
      treated eyes, and the complete regression rate in the two groups became identical
      (25%; p=1.000); partial regression rates were 70% vs 65%. In the subgroup of
      Avastin-treated eyes, multivariate analysis identified hemoglobin A1c as the
      strongest predictor of proliferative diabetic retinopathy recurrence (p=0.033).
      CONCLUSIONS: Intravitreal bevacizumab remarkably augmented the short-term
      response to scatter panretinal laser photocoagulation in high-risk characteristic
      proliferative diabetic retinopathy but the effect was short-lived, as many of the
      eyes showed rapid recurrence. Alternative dosing (multiple and/or periodic
      intravitreal Avastin injections) is recommended for further evaluation.

PMID- 18320521
TI  - Prognostic factors associated with outcomes after giant retinal tear management
      using perfluorocarbon liquids.
AB  - PURPOSE: To identify prognostic factors for visual acuity and anatomic outcomes
      associated with giant retinal tear management using intraoperative
      perfluorocarbon liquids. METHODS: All patients with giant retinal tears without
      proliferative vitreoretinopathy (PVR) who underwent management with
      intraoperative perfluorocarbon liquids between 1994 and 2005 were reviewed.
      RESULTS: The study included 115 patients (117 eyes), 93 (80.9%) males and 22
      (19.1%) females, with a mean age of 30.3+/-15.2 years. Mean follow-up period was
      29.7+/-26.7 months. Success rate with primary procedure was 78.6%, which
      increased to 94% with multiple surgeries. On univariate analysis, factors
      significantly associated with final visual acuity better than 20/200 included
      phakic/clear lens at presentation (p=0.0113), partial retinal detachment
      (p=0.0233), absence of all postoperative complications (p=0.0122), absence of
      recurrent retinal detachment (p=0.0406), and absence of postoperative PVR
      (p=0.0062). Logistic regression analysis highlighted that phakic/clear lens at
      presentation, unfolded flap of the giant tear, absence of postoperative cataract,
      and absence of postoperative PVR were associated with final visual acuity better
      than 20/200. On univariate analysis, use of gas tamponade was significantly
      associated with recurrent retinal detachment (p=0.0190). Logistic regression
      analysis highlighted that placement of an encircling scleral buckle and use of
      silicone oil tamponade were associated with anatomic reattachment with primary
      procedure. CONCLUSIONS: Encircling scleral buckling and silicone oil tamponade
      decrease the risk of recurrent retinal detachment.

PMID- 18320522
TI  - Hess Lancaster screen test with the head tilted: a useful test in the diagnosis
      of bilateral fourth nerve palsies.
AB  - PURPOSE: To introduce Hess Lancaster screen test performed with the head tilted
      as a new ancillary test to help in the diagnosis of bilateral superior oblique
      (SO) nerve paresis. METHODS: Three patients with clinical diagnosis of acquired
      bilateral fourth nerve paresis, three with clinical diagnosis of acquired
      unilateral fourth nerve paresis, and three normal subjects were tested with Hess
      Lancaster test in the nine positions of gaze with their heads straight and with
      their heads tilted to each side. Test results were compared and data were
      analyzed. RESULTS: Hess Lancaster test of all patients with bilateral SO palsy
      performed with their heads straight showed unilateral SO underaction, but when
      the test was carried out with the head tilted to each side findings were positive
      for ipsilateral SO underaction and ipsilateral hypertropia for both sides. In
      those patients with unilateral SO palsy, Lancaster test was positive for SO
      underaction when the head was in straight position and when it was tilted to the
      side of the paretic muscle, but it was almost normal with the head tilted to the
      opposite side. Normal subjects did not show any abnormality regardless of the
      head position. CONCLUSIONS: Bilateral SO palsies are sometimes difficult to
      diagnose for they might be masked. Hess Lancaster test carried out with the head
      tilted to both sides could help in the diagnosis of bilateral SO palsies.

PMID- 18320523
TI  - Congenital ocular motor apraxia.
AB  - PURPOSE: Congenital ocular motor apraxia is a rare disease characterized by
      defective or absent voluntary and optically induced horizontal saccadic
      movements. Jerky head movements or thrusts on attempted lateral gaze are a
      compensatory sign. Most affected children have delayed motor and speech
      development. Cases associated with systemic diseases, neurologic maldevelopment,
      metabolic deficits, and chromosomal abnormalities have been described. METHODS:
      Case report and review of the scientific literature. RESULTS: The authors
      describe the ophthalmologic, pediatric, and neurologic evaluations and follow up
      of a child with impaired horizontal saccades, jerky head movements, and delayed
      motor and speech development. CONCLUSIONS: Congenital ocular motor apraxia is an
      uncommon disorder of ocular motility. Even so, ophthalmologists should be aware
      of the developmental delay and the other associated conditions, in order to grant
      the patients the multidisciplinary assistance they often require.

PMID- 18320524
TI  - The importance of cyclotorsional changes in refractive surgery.
AB  - PURPOSE: To provide evidence of the importance of a precise record of torsional
      alterations in all patients about to undergo refractive surgery and particularly
      in patients with latent strabismus that may become decompensated due to the
      dissociation phenomenon produced during different surgical procedures that result
      in fixation loss. METHODS: Using 3D-VOG video-oculography, the authors analyzed
      the horizontal, vertical, and torsional movements of each eye after inducing
      fixation loss in one and both eyes in a patient with well-compensated dissociated
      vertical deviation (DVD). As the dissociated techniques, Posner maneuver and the
      placing of Bagolini filters with increasing densities by means of the
      Bielschowsky phenomenon, both pathognomonic of DVD. RESULTS: The authors observed
      not only horizontal and vertical alterations, but also cyclotorsional alterations
      which may even exceed 15 degrees depending on the resulting dissociation
      component. CONCLUSIONS: In view of the obtained results, the authors consider it
      important to conduct a meticulous study of ocular motility in all patients about
      to undergo refractive surgery, especially in the case of high astigmatism to rule
      out possible latent strabismus that may condition cyclotorsional alterations
      important in refractive surgery.

PMID- 18320525
TI  - Penetrating keratoplasty in a newborn: case report and analysis of current
      surgical trends in Italy.
AB  - PURPOSE: The aims of this study were to describe bilateral penetrating
      keratoplasty (PK) in a newborn and to analyze the data of PKs performed in Italy
      during the 5-year period 1999-2003 in children under 4 years of age. METHODS: A
      male newborn had PK at age 3 months and 5 months for near-blindness secondary to
      severe congenital corneal clouding in both eyes. The infant''s explanted corneas
      were subjected to histochemical and ultrastructural analyses. Data regarding the
      number of PKs performed in Italy on 0-4-year-olds were obtained from the Web site
      of the Italian Ministry of Health. RESULTS: The postoperative courses were
      uncomplicated, and 42 months of follow-up data show bilateral graft transparency
      and substantial improvement in visual acuity despite high-grade myopia and
      nystagmus. At the ultrastructural level, the main alterations involved the
      endothelial cells and Descemet membrane. A total of 45 PKs were performed in
      Italy on patients 0-4 years old from 1999 through 2003; only nine involved babies
      under 1 year of age. CONCLUSIONS: In babies with congenital corneal opacities,
      early PK can reduce severe amblyopia. However, the risk of intra- and
      postoperative complications in PK is high. Based on the 42-month follow-up, the
      anatomic and functional results achieved in the current patient are satisfactory
      despite the presence of nystagmus and postoperative high-grade myopia. This study
      shows that PKs are rarely performed, in Italy, in children aged 0-4 years, and
      very few are done during the first year of life.

PMID- 18320526
TI  - Mycobacterium chelonae keratitis in a patient with Sjogren's syndrome.
AB  - PURPOSE: In this report a case of Mycobacterium chelonae keratitis in a patient
      without any previously described risk factors is described. The only risk factor
      found was a rheumatoid arthritis related Sjogren''s syndrome. METHODS: Case
      report. RESULTS: A 60-year-old woman was referred to the hospital with an
      infectious keratitis of the left eye of 3 months duration, unresponsive to
      empirical therapy with ofloxacin and tobramycin drops. Her medical history
      included a longstanding rheumatoid arthritis and a secondary ocular surface
      syndrome. Upon arrival the left eye showed diffuse corneal edema and centrally
      several large infiltrates with fluffy edges, surrounded by several smaller
      satellite infiltrates. The cornea was scraped for culture and grew M chelonae and
      sensitivity testing showed sensitivity to ciprofloxacin, clofazimine, and
      clarithromycin. Systemically, ciprofloxacin 750 mg and clarithromycin 500 mg
      twice daily were prescribed orally. Topical therapy consisted of topical
      erythromycin 10 mg/mL and ofloxacin 3 mg/mL every 2 hours. Treatment was
      continued for a total of 10 months during which the infiltrates cleared
      completely, but the central cornea remained scarred. CONCLUSIONS: M chelonae can
      be a cause of infectious keratitis in patients without known risk factors for
      rapidly growing mycobacterium keratitis. Especially in the case of ocular
      infections that show no response to regular antibacterial treatment,
      mycobacterial infection should be considered. Good communication between the
      ophthalmologist and the microbiologist is crucial for a rapid diagnosis.

PMID- 18320527
TI  - Single-session photodynamic therapy combined with intravitreal bevacizumab for
      neovascular age-related macular degeneration.
AB  - PURPOSE: To evaluate the efficacy of combined single-session photodynamic therapy
      (PDT) and intravitreal bevacizumab (IVB) for treatment of neovascular age-related
      macular degeneration (AMD). METHODS: In a prospective interventional case series,
      patients with subfoveal choroidal neovascularization (CNV) underwent PDT followed
      by 1.25 mg IVB injection. Best-corrected visual acuity (BCVA) and optical
      coherence tomography (OCT) measurements were repeated at 6-week intervals and
      fluorescein angiography was performed after 12 weeks and when considered
      necessary thereafter. Repeat injections of IVB were performed based on
      fluorescein angiographic evidence of CNV leakage. RESULTS: Fourteen eyes were
      included in this study. Mean follow-up was 52.4+/-15.2 weeks (range: 26-74
      weeks). Initially, mean BCVA was 0.80+/-0.42 logMAR and mean central macular
      thickness (CMT) was 308+/88 microm. At week 12, BCVA improved to 0.62+/-0.47
      logMAR (p=0.006) and CMT reduced to 186+/-53 microm (p=0.003). Corresponding
      results were 0.53+/-0.52 logMAR (p=0.02) and 193+/-78 microm (p=0.002) after 24
      weeks. A second IVB injection was performed in 13 eyes with a mean interval of
      16.3+/-5.9 weeks. CONCLUSIONS: Combination therapy with single-session PDT and
      IVB can improve vision and reduce CMT in neovascular AMD. Repeat IVB injections
      may maintain the visual gain from the initial combination therapy.

PMID- 18320528
TI  - Spontaneous resolution of vitreomacular traction following ranibizumab (Lucentis)
      injection.
AB  - PURPOSE: Spontaneous resolution of vitreomacular traction syndrome in diabetic
      patients is a rare phenomenon that has been poorly described in the literature.
      METHODS: Case presentation. RESULTS: The authors present a case of spontaneous
      resolution of vitreomacular traction following intravitreal administration of
      ranibizumab. CONCLUSIONS: In patients with vitreomacular traction syndrome and
      diabetic macular edema, the combination of the possible vitreous liquefaction and
      mechanical increase of vitreous volume caused by an intravitreal injection with a
      degree of reduction in retinal thickness caused by the effect of vascular
      endothelial growth factor inhibition could play a role in the resolution of
      vitreomacular traction.

PMID- 18320529
TI  - Vitreoretinal surgery for retinal detachment in retinochoroidal colobomata.
AB  - PURPOSE: To report the management and outcome of retinal reattachment surgery in
      retinochoroidal coloboma. METHODS: Four patients with retinochoroidal colobomata
      presented to the Bristol Eye Hospital (a UK tertiary referral center for
      vitreoretinal surgery) with retinal detachment. INTERVENTION: All were type II
      colobomatous detachments (three patients with type IIB, one patient with type
      IID). All eyes underwent vitrectomy with endolaser and/or cryotherapy and three
      eyes underwent scleral buckling. Two eyes had internal tamponade with gas (SF6,
      C3F8) while the other two had silicone oil. Endolaser was applied over healthy
      retinal pigment epithelium. RESULTS: At last follow-up, all (100%) remained
      attached, with no recurrences. Three patients achieved visual acuity of 6/120 or
      better and were able to perform satisfactory near work with appropriate
      magnifiers. The last patient began with hand movement vision and retained similar
      vision but subjectively felt more navigational. CONCLUSIONS: Good anatomic and
      functional outcomes can be achieved in this patient group with combined
      vitrectomy with or without scleral buckling surgery. Endolaser retinopexy is
      effective over healthy RPE at the margin of the coloboma combined with either gas
      or oil internal tamponade.

PMID- 18320530
TI  - Is there alteration in aortic stiffness in Leber hereditary optic neuropathy?
AB  - PURPOSE: Leber hereditary optic neuropathy (LHON) is recognized as the most
      common cause of isolated blindness in young men. The current study was designed
      to test whether LHON as a mitochondrial disease is associated with vascular
      functional alterations characterized by aortic elastic properties during
      echocardiography. METHODS: A total of 19 patients with typical features of LHON
      aged 42+/-13 years (10 males) were included. Their results were compared to 19
      age- and gender-matched healthy controls. Aortic stiffness index was calculated
      from the echocardiographically derived aortic diameters and the clinical blood
      pressure data. RESULTS: In this patient population, the point mutation was
      present in 3460G>A position in five cases, in 11778G>A position in five cases,
      and in 14484T>C position in nine patients. Diastolic aortic diameter (26.0+/-2.5
      mm vs 28.4+/-4.1 mm, p<0.05) and aortic stiffness index (5.1+/-2.6 vs 12.0+/-7.9,
      p<0.05) were significantly increased in LHON patients compared to controls.
      CONCLUSIONS: Aortic stiffness can be increased in LHON disease, but further
      studies are warranted to confirm these findings in a larger LHON patient
      population with a more reliable method focusing on the pathophysiologic
      background.

PMID- 18320531
TI  - Hepatitis C virus presumably associated bilateral consecutive anterior ischemic
      optic neuropathy.
AB  - PURPOSE: To report a case of bilateral nonarteritic anterior ischemic optic
      neuropathy (NAION) in a hepatitis C (HCV) infected patient and demonstrate the
      relationship between HCV and the development of NAION. METHODS: Case report.
      RESULTS: A 43-year-old woman with chronic HCV infection and long-term euthyroid
      autoimmune thyroiditis suddenly lost vision in her right eye, and 6 months later
      in her left eye, due to NAION. Slightly elevated levels of aminotransferases
      suggested liver infection activity. Anti-HCV antibody was detected; the genotype
      of the virus was 1b and the viral RNA level was 1.8 x 106 IU/mL. Liver biopsy
      proved chronic active hepatitis (Ishak score grading: 7, staging: 2). Except for
      the elevated levels of antithyroid antibodies and a weak antinuclear factor, the
      detailed laboratory examinations (thrombophilia, cryoglobulin, anticardiolipin
      antibodies, co-infections) revealed no other abnormalities; a causative
      relationship between the underlying chronic hepatitis C and bilateral NAION
      therefore seems probable. The patient was treated with pegylated interferon and
      ribavirin for 1 year and a sustained viral remission could be achieved. Her
      vision has neither improved nor deteriorated further. CONCLUSIONS: This appears
      to be the first reported case of bilateral NAION presumably caused by HCV
      infection.

PMID- 18320532
TI  - Optociliary shunt vessels in compressive optic neuropathy by the intracranial
      internal carotid artery.
AB  - PURPOSE: To report a clinical case of optic nerve compression by supraclinoidal
      internal carotid artery associated with optociliary shunt vessels. METHODS: A 78
      year-old woman with the clinical triad of left visual loss, ipsilateral optic
      disc pallor, and retinochoroidal (optociliary) shunt vessels is reported. She
      complained of loss of vision in the left eye of 2 years'' duration. RESULTS: A
      diffuse depression of the visual field was found in the affected eye. Magnetic
      resonance imaging revealed left optic nerve compression by the supraclinoidal
      internal carotid artery. CONCLUSIONS: The occurrence of optociliary shunt
      vessels, visual loss, and optic atrophy is a nonspecific sign of chronic optic
      nerve compression and in some instances may be falsely localized.

PMID- 18320533
TI  - Comparison of visual function and ocular hemodynamics between pre- and post
      menopausal women.
AB  - PURPOSE: The incidence of eye disease increases with age and can often be linked
      to worsening cardiovascular function and increasing intraocular pressure.
      Estrogen is known to have vasodilatory effects in the systemic circulation.
      Decreased estrogen levels during menopause may therefore complicate or contribute
      to ocular pathologies as estrogen receptors are found in both retinal and
      choroidal tissue. The purpose of this investigation was to determine the effects
      of menopause on visual function and cardiovascular and ocular hemodynamics.
      METHODS: Twelve premenopausal and 24 postmenopausal women were evaluated at the
      Indiana University School of Medicine during a single study visit. Vision
      screening and ocular blood flow evaluations were performed, including blood
      pressure, heart rate, visual acuity, contrast sensitivity, intraocular pressure,
      and retinal capillary and retrobulbar blood flow imaging. Vision and ocular
      hemodynamics were compared using unpaired Student t-tests with p<0.05 regarded as
      statistically significant. RESULTS: The premenopausal group had significantly
      lower heart rate (-16.1 b/m, p=0.0001) and systolic blood pressure (-17.7 mmHg,
      p=0.003) than postmenopausal subjects. Contrast sensitivity was significantly
      higher (measured in log units) in premenopausal women in both the right (0.25,
      p=0.039; 0.16, p=0.039) and left (0.45, p=0.001; 0.27, p=0.032) eyes at 9 and 18
      cycles per degree, respectively. Premenopausal women also had significantly lower
      intraocular pressure in both the right (-2.19 mmHg, p=0.024) and left (-1.74
      mmHg, p=0.035) eyes. Total ocular perfusion was not significantly different
      between groups. CONCLUSIONS: This pilot work suggests that postmenopausal women
      have lower contrast sensitivity detection and elevated intraocular pressures
      compared to premenopausal women. Premenopausal women have lower cardiovascular
      risk factors, while total ocular circulation was similar to postmenopausal women.

PMID- 18320535
TI  - Laparoscopic peritoneal lavage for generalized peritonitis due to perforated
      diverticulitis (Br J Surg 2008; 95: 97-101).

PMID- 18320536
TI  - Differentiation of three pairs of Boc-beta,gamma- and gamma,beta-hybrid peptides
      by electrospray ionization tandem mass spectrometry.
AB  - A new series of Boc-N-beta(3), gamma(4)-/gamma(4), beta(3)-isomeric hybrid
      peptides (containing repeats of beta(3)-Caa and gamma(4)-Caa's, Caa = C-linked
      carbo beta(3)-/gamma(4)-amino acids derived from D-xylose) have been
      differentiated by both positive and negative ion electrospray ionization (ESI)
      ion-trap and high resolution quadrupole time-of-flight/tandem mass spectrometry
      (Q-TOF MS/MS). MS(n) of protonated isomeric peptides and [M+H-Boc+H](+) produce
      characteristic fragmentation involving the peptide backbone, the Boc-group, and
      the side chain. The positional isomers are differentiated from one another by the
      presence of y(n)(+), b(n)(+), and other fragment ions of different m/z values. It
      is observed that the peptides with beta-Caa at the N-terminus produce extensive
      fragmentation, whereas gamma-Caa gave rise to much less fragmentation. Peptides
      with gamma-Caa at the N-terminus lose NH(3), whereas this process is absent for
      the carbopeptides with beta-Caa at the N-terminus. Two pairs of dipeptide
      diastereomers are clearly differentiated by the collision-induced dissociation
      (CID) of their protonated molecules. The loss of 2-methylprop-1-ene is more
      pronounced for Boc-NH-(R)-beta-Caa-(R)-gamma-Caa-OCH(3) (6) and Boc-NH-(R)-gamma
      Caa-(R)-beta-Caa-OCH(3) (12), whereas it is insignificant or totally absent for
      its protonated diastereomeric pair Boc-NH-(S)-beta-Caa-(S)-gamma-Caa-OCH(3) (1)
      and Boc-NH-(S)-gamma-Caa-(S)-beta-Caa-OCH(3) (7). Further, ESI negative ion
      tandem mass spectrometry has also been found to be useful for differentiating
      these isomeric peptide acids.

PMID- 18320537
TI  - Current management of bile duct injury.

PMID- 18320538
TI  - Dehydrogenation of tertiary amines in matrix-assisted laser desorption/ionization
      time-of-flight mass spectrometry.
AB  - In the matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI TOF MS) analysis of various compounds synthesized in our
      laboratory, strong [M - H]+ ion peaks were often observed for the molecules with
      tertiary amino groups. In this work, the MALDI TOF MS behavior of two groups of
      compounds that incorporate tertiary amino moieties was investigated. One group is
      bisurea dimethylanilines (BUDMAs) prepared for the study of molecular recognition
      in thermoplastic elastomers, and the other group is the poly(propylene imine)
      diaminobutane dendrimers. The results clearly demonstrate the appearance of the
      [M - H]+ ions. In order to understand the possible mechanisms for the generation
      of these ions, a series of model compounds, ranging from primary to tertiary
      amines, were investigated. Unlike the tertiary amines, no [M - H]+ ion peaks were
      recorded for the primary amines, and only barely detectable ones, if any, for
      some secondary amines. It appears that the tertiary amino groups play an
      important role in the formation of these ions. In addition to MALDI TOF MS
      analysis, these samples were also applied to electrospray ionization (ESI) MS
      where no [M - H]+ ions were observed. The results indicate that the generation of
      [M - H]+ ion is due to the unique MALDI conditions and is likely to be formed via
      dehydrogenation of a protonated tertiary amine resulting in an N=C double bond.
      The absence of [M - H]+ ion peaks for the primary and secondary amines is
      probably because upon their formation these ions could easily transfer one proton
      to the corresponding amines in the MALDI gas-phase plume, yielding neutral imines
      that cannot be detected by MS.

PMID- 18320539
TI  - Chemical derivatization of peptides containing phosphorylated serine/threonine
      for efficient ionization and quantification in matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry.
AB  - We describe a useful method for the efficient ionization and relative
      quantification of peptides containing serine/threonine phosphorylation sites.
      This method is based on beta-elimination of the phosphate group from
      serine/threonine phosphorylation sites under alkaline conditions, followed by
      Michael addition reaction with N-(2-mercaptoethyl)-6-methylnicotinamide (MEMN).
      As a result of the derivatization reaction, the negatively charged phosphate
      group is substituted with the nicotinoyl moiety to improve the ionization
      efficiency of the derivatized peptide. The combination of d(3)-labeled MEMN (d(3)
      MEMN) and MEMN (d(0)-MEMN) generates a 3 Da mass difference between d(3)-MEMN
      labeled and d(0)-MEMN-labeled peptides, which is a useful signature for the
      identification of peptides containing serine/threonine phosphorylation sites in
      the matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrum. Moreover, the mass difference is useful for the quantitative analysis
      of serine/threonine phosphorylation in proteins. In this paper, we describe the
      synthesis of d(0)/d(3)-labeled MEMN and an application of our approach to model
      peptides and proteins.

PMID- 18320540
TI  - Assessing the stable carbon isotopic composition of intercellular CO2 in a CAM
      plant using gas chromatography-combustion-isotope ratio mass spectrometry.
AB  - Most of the literature focused on internal CO(2) (Ci) determinations in plants
      has used indirect methods based on gas-exchange estimations. We have developed a
      new method based on the capture of internal air gas samples and their analysis by
      gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). This
      method provided a direct measure of intercellular CO(2) concentrations combined
      with stable carbon isotopic composition in O. ficus-indica plants. Plants were
      grown at both ambient and elevated CO(2) concentration. During the day period,
      when the stomata are closed, the Ci was high and was very (13)C-enriched in both
      ambient and elevated CO(2)-grown plants, reflecting Rubisco's fractionation (this
      plant enzyme has been shown to discriminate by 29 per thousand, in vitro, against
      (13)CO(2)). Other enzyme fractionations involved in C metabolism in plants, such
      as carbonic anhydrase, could also be playing an important role in the diurnal
      delta(13)C enrichment of the Ci. During the night, when stomata are open, Ci
      concentrations were higher in elevated (and the corresponding delta(13)C values
      were more (13)C-depleted) than in ambient CO(2)-grown plants.

PMID- 18320541
TI  - Classification of vegetable oils according to their botanical origin using sterol
      profiles established by direct infusion mass spectrometry.
AB  - A simple and quick method to classify vegetable oils according to their botanical
      origin, based on direct infusion of sterol extracts into a mass spectrometer, was
      developed. Using mass spectrometry (MS) with either an electrospray ionization or
      an atmospheric pressure photoionization source, followed by linear discriminant
      analysis of the mass spectral data, oil samples corresponding to eight different
      botanical origins were perfectly classified with an excellent resolution among
      all the categories. An excellent correlation between the sterol profiles obtained
      by MS and by the official gas chromatography (with flame ionization detection)
      method was obtained. Thus, the proposed method is a promising alternative for
      sterol fingerprinting of vegetable oils, with the advantage that prior
      chromatographic separation is not required.

PMID- 18320542
TI  - Gas chromatography/mass spectrometry analysis of triacetone triperoxide (TATP)
      degradation products.
AB  - Interest in the analysis and detection of triacetone triperoxide (TATP) and other
      organic peroxides has increased in recent years. Also of interest is the
      degradation and decomposition of the peroxides, not only to gain more detailed
      chemical information from organic peroxide samples, but also to investigate
      possible new procedures or mechanisms for chemical neutralisation. This report
      investigates the chemical degradation products of TATP after it has been treated
      with different acids within a sealed system over a period of 14 days. The samples
      were collected and analysed by solid-phase microextraction (SPME) and direct
      liquid injection gas chromatography/mass spectrometry (GC/MS). The results of the
      experiments indicate that the rate of chemical degradation of TATP and the
      products formed are dependent on the type of acid. The observed differences
      enables the type of acid used in the degradation process to be determined,
      provide complementary information to identify the presence of TATP, and possibly
      indicate new pathways that may be used to chemically neutralise TATP.

PMID- 18320543
TI  - Dual negative precursor ion scan approach for rapid detection of glutathione
      conjugates using liquid chromatography/tandem mass spectrometry.
AB  - Screening for conjugates formed by the tripeptide glutathione with new chemical
      entities is an essential step during the drug discovery process, as the formation
      of these conjugates serves as an indicator for the presence of reactive
      electrophilic intermediates. To increase the selectivity and throughput of this
      analysis, various mass spectral scan types have evolved over time. Historically,
      samples were analyzed under positive ionization conditions for the neutral loss
      of m/z 129 (loss of the pyroglutamic acid moiety from glutathione); however, more
      recently, negative precursor ion scanning for the loss of m/z 272 (deprotonated
      gamma-glutamyl-dehydroalanyl-glycine from glutathione) has emerged as a more
      selective tool. Further increasing the selectivity, we report on an extension of
      this methodology by incorporating a simultaneous dual negative precursor ion scan
      for two commonly observed ion fragments from glutathione conjugates, m/z 272 and
      254 (the dehydrated form of m/z 272). This negative dual precursor ion scan
      methodology was first validated using substrates known to undergo metabolic
      bioactivation (diclofenac, carbamazepine, and 3-methyl indole) and has then been
      applied to the routine analysis of proprietary compounds undergoing active lead
      optimization. In comparison to alternative scan methodologies, the increased
      selectivity offered by this simultaneous dual precursor method results in a
      reduction in the generation of false positive results as well as reduced data
      interpretation time.

PMID- 18320544
TI  - Influence of mass resolution on species matching in accurate mass and retention
      time (AMT) tag proteomics experiments.
AB  - Diverse mass spectrometric instruments have been used to provide data for
      accurate mass and retention time (AMT) tag proteomics analyses, including ion
      trap, quadrupole time-of-flight, and Fourier transform mass spectrometry (FTMS).
      An important attribute of these instruments, beside mass accuracy, is their
      spectral resolution. In fact, the ability to separate peaks with close m/z values
      is likely to play a major role in enabling species identification and matching in
      analyses of very complex proteomics samples. In FTMS, resolution is directly
      proportional to the detection period and can therefore be easily tuned. We took
      advantage of this feature to investigate the effect of resolution on species
      identification and matching in an AMT tag experiment. Using an Arabidopsis
      thaliana chloroplast protein extract as prototypical 'real-life' sample, we have
      compared the number of detected features, the optimal mass tolerance for species
      matching, the number of matched species and the false discovery rate obtained at
      various resolution settings. It appears that while the total number of matches is
      not significantly affected by a reduction of resolution in the range
      investigated, the confidence level of identifications significantly drops as
      evidenced by the estimated false discovery rate.

PMID- 18320545
TI  - Direct analysis of illicit drugs by desorption atmospheric pressure
      photoionization.
AB  - The feasibility of desorption atmospheric pressure photoionization (DAPPI) in the
      direct analysis of illicit drugs was demonstrated by the analysis of confiscated
      drug samples of various forms such as tablets, blotter paper, and plant resin and
      bloom. 3,4-Methylenedioxymethamphetamine (MDMA), amphetamine, phenazepam, and
      buprenorphine were detected from the analyzed tablets, lysergic acid diethylamide
      (LSD) and bromobenzodifuranylisopropylamine (bromo-Dragonfly, ABDF) from blotter
      paper, and Delta(9)-tetrahydrocannabinol (THC) and cannabinol from Cannabis
      Sativa bloom and resin. The amphetamines, phenazepam and ABDF showed protonated
      molecules independent of the solvent used, whereas buprenorphine, LSD and the
      cannabinoids showed molecular ions with toluene and protonated molecules with
      acetone as the solvent.

PMID- 18320546
TI  - Metabolism of olaquindox in rat liver microsomes: structural elucidation of
      metabolites by high-performance liquid chromatography combined with ion trap/time
      of-flight mass spectrometry.
AB  - Olaquindox (N-(2-hydroxyethyl)-3-methyl-2-quinoxalincarboxamide-1,4-dioxide) is a
      growth-promoting feed additive for food-producing animals. Its toxicity is
      closely related to the metabolism. The complete metabolic pathways of olaquindox
      are not revealed. To improve studies of the metabolism and toxicity of
      olaquindox, its biotransformation in rat liver microsomes and the structure of
      its metabolites using high-performance liquid chromatography combined with ion
      trap/time-of-flight mass spectrometry (LC/MS-ITTOF) were investigated. When
      olaquindox was incubated with an NADPH-generating system and rat liver
      microsomes, ten metabolites (M1-M10) were detected. The structures of these
      metabolites were identified from mass spectra and comparison of their changes in
      their accurate molecular masses and fragment ions with those of the parent drug.
      With the high resolution and good mass accuracy achieved by this technique, the
      elemental compositions of the metabolites and their fragment ions were exactly
      determined. The results indicate that the N --> O group reduction is the main
      metabolic pathway of olaquindox metabolism in rat liver microsomes, because
      abundant 1-desolaquindox (M2), 4-desolaquindox (M1) and bisdesoxyolaquindox (M9)
      were produced during the incubation step. Seven other minor metabolites were
      revealed which were considered to be hydroxylation metabolites, based on the
      position of the quinoxaline ring or 3-methyl group and a carboxylic acid
      derivative on the side chain at position 2 of the quinoxaline ring. Among the
      identified metabolites, five new hydroxylated metabolites (M3-M7) were found for
      the first time in rat liver microsomes. This work will conduce to complete
      clarification of olaquindox metabolism, and improve the in vivo metabolism of
      olaquindox in food animals.

PMID- 18320547
TI  - In situ derivatization/solid-phase microextraction coupled with gas
      chromatography/negative chemical ionization mass spectrometry for the
      determination of trichloroethylene metabolites in rat blood.
AB  - An in situ derivatization solid-phase microextraction (SPME) method has been
      developed for the determination of the trichloroethylene (TCE) metabolites,
      trichloroacetic acid (TCA), dichloroacetic acid (DCA) and trichloroethanol
      (TCOH), in rat blood. The analytical procedure involves derivatization of TCA and
      DCA to their ethyl esters with acidic ethanol, headspace sampling using SPME, and
      gas chromatography/negative chemical ionization mass spectrometry (GC/NCI-MS)
      determination. Parameters affecting both derivatization efficiency and the
      headspace SPME procedure, such as the concentration of sulfuric acid, amount of
      ethanol, derivatization-extraction temperature and time, sample preheating time,
      agitator speed and desorption conditions, were optimized. The method showed good
      linearity over the range of 1-1000 ng/mL in rat blood for each metabolite with
      correlation coefficients (R(2)) higher than 0.99. The intra-day and inter-day
      precision and accuracy were less than 10%. The relative recoveries for all
      analytes were greater than 84%. Validation results demonstrated that selected ion
      monitoring of the (35)Cl and (37)Cl isotopes using NCI resulted in reliable and
      sensitive quantitation of all three TCE metabolites. This validated method was
      successfully applied to study the toxicokinetic behavior of TCE metabolites
      following a 1 mg/kg oral dose of TCE.

PMID- 18320549
TI  - Development and validation of an inductively coupled plasma mass spectrometry
      method for quantification of levothyroxine in dissolution studies.
AB  - A simple, sensitive and reproducible inductively coupled plasma mass spectrometry
      (ICP-MS) method for the direct determination of levothyroxine (T4), based on the
      analysis of iodide content, in aqueous media was developed. The sample
      preparation consisted of addition of antimony, as the internal standard, and
      dilution with a 0.5% ammonia solution. The analytes were quantified at m/z 126.90
      and 120.90 for iodide and antimony, respectively. The assay was linear in the
      concentration range of 0.1-50 ng/mL for iodide and 0.3-100 ng/mL for T4. The
      method was precise and accurate with lower limits of quantification (LLOQs) of
      0.1 ng/mL for iodide and 0.3 ng/mL for T4. The inter-day accuracy was >94% for
      both analytes and the coefficient of variation (%CV) was less than 5%. The method
      has successfully been used for dissolution studies of T4 formulations and holds
      immense promise as a simple, precise and sensitive analytical technique for T4
      concentration determination in in vitro studies.

PMID- 18320548
TI  - Serum biomarker profiling by solid-phase extraction with particle-embedded micro
      tips and matrix-assisted laser desorption/ionization mass spectrometry.
AB  - One of the main challenges in high-throughput serum profiling by matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is
      the development of proteome fractionation approaches that allow the acquisition
      of reproducible profiles with a maximum number of spectral features and minimum
      interferences from biological matrices. This study evaluates a new class of solid
      phase extraction (SPE) pipette tips embedded with different chromatographic media
      for fractionation of model protein digests and serum samples. The materials
      embedded include strong anion exchange (SAX), weak cation exchange (WCX), C18,
      C8, C4, immobilized metal affinity chromatography (IMAC) and zirconium dioxide
      particles. Simple and rapid serum proteome profiling protocols based on these SPE
      micro tips are described and tested using a variety of MALDI matrices. We show
      that different types of particle-embedded SPE micro tips provide complementary
      information in terms of the spectral features detected for beta-casein digests
      and control human serum samples. The effect of different sample pretreatments,
      such as serum dilution and ultrafiltration using molecular weight cut-off
      membranes, and the reproducibility observed for replicate experiments, are also
      evaluated. The results demonstrate the usefulness of these simple SPE tips
      combined with offline MALDI-TOF MS for obtaining information-rich serum profiles,
      resulting in a robust, versatile and reproducible open-source platform for serum
      biomarker discovery.

PMID- 18320550
TI  - Quantitative determination of progesterones and corticosteroids in human urine
      using gas chromatography/mass spectrometry: application to pelvic organ prolapse
      patients.
AB  - A quantitative analytical method using gas chromatography/mass spectrometry
      (GC/MS) to determine urinary concentrations of eight progesterones and
      corticosteroids has been developed. After enzymatic hydrolysis with beta
      glucouronidase/arylsulfatase, urine samples were extracted by simple one-step
      solid-phase extraction. Obtained extracts were derivatized with a mixture of N
      methyl-N-(trimethylsilyl)trifluoroacetamide/ammonium iodide/dithiothreitol and
      determined by GC/MS in selected ion monitoring mode to increase the sensitivity.
      d(4)-Cortisol and d(9)-progesterone were used as internal standards for two
      different steroid groups. The linear correlation coefficient was in the range of
      0.9913 to 0.9998 and recoveries were over 80% for all compounds. Precision and
      accuracy were in the range of 0.9-18.1 and 84.1-118.7%, respectively. The limit
      of quantitation (LOQ) was 10 ng/mL for 11-deoxycorticosterone and 21
      deoxycortisol and 5 ng/mL for all other analytes. The developed method was
      successfully applied on pelvic organ prolapsed patients (n = 10, age: 67.9 +/-
      4.9) and post-menopausal (n = 10, age: 63.6 +/- 5.5) control women. Urinary
      levels of most progesterones and corticosteroids except 11-deoxycorticosterone
      decreased but only that of 17 alpha-hydroxyprogesterone significantly decreased
      in patients compared with the control groups. Thus, it is concluded that
      progesterones could be a factor in the pathogenesis of pelvic organ prolapse,
      and, among them, 17 alpha-hydroxyprogesterone could be a biomarker for pelvic
      organ prolapse.

PMID- 18320551
TI  - Assessing the association between environmental impacts and health outcomes: a
      case study from Florida.
AB  - The Centers for Disease Control and Prevention (CDC) created the Environmental
      Public Health Tracking (EPHT) program to integrate hazard monitoring, exposure,
      and health effects surveillance into a cohesive tracking network. Part of
      Florida's effort to move toward implementation of EPHT is to develop models of
      the spatial and temporal association between myocardial infarctions (MIs) and
      ambient ozone levels in Florida. Existing data were obtained from Florida's
      Agency for Health Care Administration, Florida's Department of Environmental
      Protection, the U.S. Census Bureau, and CDC's Behavioral Risk Factor Surveillance
      System. These data were linked by both ignoring spatial support and using block
      kriging, a support-adjusted approach. The MI data were indirectly standardized by
      age, race/ethnicity, and sex. The state of Florida was used as the comparison
      standard to compute the MI standardized event ratio (SER) for each county and
      each month. After the data were linked, global models were used initially to
      relate MIs to ambient ozone levels, adjusting for covariates. The global models
      provide an estimated relative MI SER for the state. Realizing that the
      association in MIs and ozone might change across locations, local models were
      used to estimate the relative MI SER for each county, again adjusting for
      covariates. Results differed, depending on whether the spatial support was
      ignored or accounted for in the models. The opportunities and challenges
      associated with EPHT analyses are discussed and future directions highlighted.

PMID- 18320552
TI  - Can electrospray ionization help the characterization of iron gall inks?
      Investigation on the interactions of gallic acid with iron ions in aqueous
      solutions.
AB  - In the present work, an investigation has been conducted by electrospray
      ionization (ESI) experiments to characterize the structures of iron gall ink
      complexes in solution. Simple mono and polyphenolic acid molecules added to iron
      sulfate salts were chosen to model the recipes of ink composition. Theoretical
      calculations have been used (1) to determine the stability of the ionic complexes
      generated in the gas phase, (2) to explain which structures are more likely
      generated in the electrospray ion source, and (3) to determine which mechanisms
      are likely involved in their formation. Fragmentation pathways of the derived
      structures have also been investigated and rationalized to facilitate the
      interpretation of the data obtained under collisionally induced dissociation
      (CID) conditions.The present study confirms the assumption that ESI experiments
      with ions that are preformed in solution must be considered carefully. As a
      matter of fact, the study of ion formation mechanisms in the ion source is
      necessary to establish relationships between the ion structures in the condensed
      phase and the gas phase.

PMID- 18320553
TI  - Application of fractional mass for the identification of peptide-oligonucleotide
      cross-links by mass spectrometry.
AB  - A method has been developed to identify oligonucleotide-peptide heteroconjugates
      by accurate mass measurements using MS. The fractional mass (the decimal fraction
      mass value following the monoisotopic nominal mass) for peptides and
      oligonucleotides is different due to their differing molecular compositions. This
      property has been used to develop the general conditions necessary to
      differentiate peptides and oligonucleotides from oligonucleotide-peptide
      heteroconjugates. Peptides and oligonucleotides generated by the theoretical
      digestion of various proteins and nucleic acids were plotted as nominal mass
      versus fractional mass. Such plots reveal that three nucleotides cross-linked to
      a peptide produce enough change in the fractional mass to be recognized from non
      cross-linked peptides at the same nominal mass. Experimentally, a Cytochrome c
      digest was spiked with an oligonucleotide-peptide heteroconjugate and conditions
      for analyzing the sample using liquid chromatography (LC)-MS were optimized. Upon
      analysis of this mixture, all detected masses were plotted on a fractional mass
      plot and the heteroconjugate could be readily distinguished from non-cross-linked
      peptides. The method developed here can be incorporated into a general proteomics
      like scheme for identifying protein-nucleic acid cross-links, and this method is
      equally applicable to characterizing cross-links generated from protein-DNA and
      protein-RNA complexes.

PMID- 18320554
TI  - New method to determine the total carbonyl functional group content in
      extractable particulate organic matter by tandem mass spectrometry.
AB  - A functional group analysis method was developed to determine the quantitative
      content of carbonyl functional groups in atmospheric particulate organic matter
      (POM) using constant neutral loss scanning-tandem mass spectrometry (CNLS-MS/MS).
      The neutral loss method consists in monitoring the loss of a neutral fragment
      produced by the fragmentation of a precursor ion in a collision cell. The only
      ions detected are the daughter ions resulting from the loss of the neutral
      fragment under study. Then, scanning the loss of a neutral fragment
      characteristic of a functional group enables the selective detection of the
      compounds bearing the chemical function under study within a complex mixture. The
      selective detection of carbonyl functional groups was achieved after
      derivatization with pentafluorophenylhydrazine (PFPH) by monitoring the neutral
      loss of C(6)F(5)N (181 amu), which was characteristic of a large panel of
      derivatized carbonyl compounds. The method was tested on 25 reference mixtures of
      different composition, all containing 24 carbonyl compounds at randomly
      determined concentrations. The repeatability and calibration tests were
      satisfying as they resulted in a relative standard deviation below 5% and a
      linear range between 0.01 and 0.65 mM with a calculated detection limit of 0.0035
      mM. Also, the relative deviation induced by changing the composition of the
      mixture while keeping the total concentration of carbonyl functional groups
      constant was less than 20%. These reliability experiments demonstrate the high
      robustness of the developed procedure for accurate carbonyl functional group
      measurement, which was applied to atmospheric POM samples.

PMID- 18320556
TI  - Laparoscopic subtotal cholecystectomy without cystic duct ligation (Br J Surg
      2007; 94: 1527-1529).

PMID- 18320558
TI  - Demonstrating safety through in-hospital mortality analysis following elective
      abdominal aortic aneurysm repair in England (Br J Surg 2008; 95: 64-71).

PMID- 18320559
TI  - Dopamine receptor D3 genotype association with greater acute positive symptom
      remission with olanzapine therapy in predominately caucasian patients with
      chronic schizophrenia or schizoaffective disorder.
AB  - OBJECTIVE: To test association of dopamine receptor D3 (DRD-3) gene polymorphisms
      with olanzapine response in genetic samples from a registration phase clinical
      trial. METHODS: Eighty-eight acutely ill patients with schizophrenia or
      schizoaffective disorder were genotyped for ser-9-gly (rs6280) and 23 other
      polymorphisms within the DRD-3 gene. Allelic association of clinical response
      (mean baseline- to-endpoint reduction in Positive and Negative Syndrome Scale
      [PANSS] total and subscores) over 6 weeks of olanzapine treatment was assessed
      using repeated measures analysis of variance. RESULTS: Ser-9-gly genotypes were
      associated with differences in PANSS total score improvement from baseline to 6
      weeks (p = 0.021). This association was most notable for improvement in positive
      symptoms (p = 0.0001), with patients with gly/gly genotype significantly more
      responsive. More patients with the gly/gly genotype had greater positive symptom
      remission (endpoint rating of minimal or none on all PANSS positive items, 39.1%)
      compared with patients with gly/ser and ser/ser genotypes (13.8%; p = 0.033). DRD
      3 polymorphisms in disequilibrium with ser-9-gly were also significantly
      associated with greater positive symptom improvement (p = 0.0009-0.021), and one
      not in complete linkage disequilibrium, with lesser improvement (p = 0.027).
      CONCLUSIONS: Gly/gly DRD-3 genotype predicted statistically and clinically
      significantly better acute positive symptom reduction compared with other ser-9
      gly genotypes in patients treated with olanzapine.

PMID- 18320560
TI  - The influence of substrate peptide length on human beta-tryptase specificity.
AB  - Combinatorial chemistry approach was applied to design chromogenic substrates of
      human beta-tryptase. The most active substrate, Ala-Ala-Pro-Ile-Arg-Asn-Lys-ANB
      NH(2), was selected from among over 9 million heptapeptides. The amide of 5-amino
      2-nitrobenzoic acid (ANB-NH(2)) attached at the C-terminus served as a
      chromophore. In order to determine the optimal length of the tryptase substrate,
      a series of N-terminally truncated fragments of this substrate was synthesized.
      Pro-Ile-Arg-Asn-Lys-ANB-NH(2), with the determined value of the specificity
      constant (k(cat)/K(M)) above 9 x 10(6) M(-1) s(-1), appeared to be the most
      specific substrate of tryptase. This substrate was twice as active as the parent
      heptapeptide substrate. We postulate that the optimal size of the pentapeptide
      substrate for the interaction with human beta-tryptase is associated with the
      unique structure of this proteinase, comprising four almost identical monomer
      subunits arranged in a square flat ring with its substrate pockets faced inside,
      forming a tetramer with a central pore that can be penetrated by this short
      peptide.

PMID- 18320561
TI  - Micelles by self-assembling peptide-conjugate amphiphile: synthesis and
      structural characterization.
AB  - The chemical synthesis by solid-phase methods of a novel amphiphilic peptide,
      peptide-conjugate amphiphile (PCA), containing in the same molecule three
      different functions: (i) the N,N-bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic
      acid (DTPAGlu) chelating agent, (ii) the CCK8 bioactive peptide, and (iii) a
      hydrophobic moiety containing four alkyl chains with 18 carbon atoms each, is
      reported. In water solution at pH 7.4, PCA self-assembles in very stable micelles
      at very low concentration [critical micellar concentration (cmc) values of 5 x
      10(-7) mol kg(-1)] as confirmed by fluorescence spectroscopy. The structural
      characterization, obtained with small-angle neutron scattering (SANS)
      measurements, indicates that the aggregates are substantially represented by
      ellipsoidal micelles with an aggregation number of 39 +/- 2 and the two micellar
      axes of about 52 and 26 A.

PMID- 18320562
TI  - Mining marine shellfish wastes for bioactive molecules: chitin and chitosan--Part
      A: extraction methods.
AB  - Legal restrictions, high costs and environmental problems regarding the disposal
      of marine processing wastes have led to amplified interest in biotechnology
      research concerning the identification and extraction of additional high grade,
      low-volume by-products produced from shellfish waste treatments. Shellfish waste
      consisting of crustacean exoskeletons is currently the main source of biomass for
      chitin production. Chitin is a polysaccharide composed of N-acetyl-D-glucosamine
      units and the multidimensional utilization of chitin derivatives including
      chitosan, a deacetylated derivative of chitin, is due to a number of
      characteristics including: their polyelectrolyte and cationic nature, the
      presence of reactive groups, high adsorption capacities, bacteriostatic and
      fungistatic influences, making them very versatile biomolecules. Part A of this
      review aims to consolidate useful information concerning the methods used to
      extract and characterize chitin, chitosan and glucosamine obtained through
      industrial, microbial and enzymatic hydrolysis of shellfish waste.

PMID- 18320563
TI  - The Taguchi methodology as a statistical tool for biotechnological applications:
      a critical appraisal.
AB  - Success in experiments and/or technology mainly depends on a properly designed
      process or product. The traditional method of process optimization involves the
      study of one variable at a time, which requires a number of combinations of
      experiments that are time, cost and labor intensive. The Taguchi method of design
      of experiments is a simple statistical tool involving a system of tabulated
      designs (arrays) that allows a maximum number of main effects to be estimated in
      an unbiased (orthogonal) fashion with a minimum number of experimental runs. It
      has been applied to predict the significant contribution of the design
      variable(s) and the optimum combination of each variable by conducting
      experiments on a real-time basis. The modeling that is performed essentially
      relates signal-to-noise ratio to the control variables in a 'main effect only'
      approach. This approach enables both multiple response and dynamic problems to be
      studied by handling noise factors. Taguchi principles and concepts have made
      extensive contributions to industry by bringing focused awareness to robustness,
      noise and quality. This methodology has been widely applied in many industrial
      sectors; however, its application in biological sciences has been limited. In the
      present review, the application and comparison of the Taguchi methodology has
      been emphasized with specific case studies in the field of biotechnology,
      particularly in diverse areas like fermentation, food processing, molecular
      biology, wastewater treatment and bioremediation.

PMID- 18320564
TI  - RNA interference: an emerging generation of biologicals.
AB  - RNA interference (RNAi) is a mechanism displayed by most eukaryotic cells to rid
      themselves of foreign double-stranded RNA molecules. RNAi has now been
      demonstrated to function in mammalian cells to alter gene expression, and has
      been used as a means for genetic discovery as well as a possible strategy for
      genetic correction. RNAi was first described in animal cells by Fire and
      colleagues in the nematode, Caenorhabditis elegans. Knowledge of RNAi mechanism
      in mammalian cell in 2001 brought a storm in the field of drug discovery. During
      the past few years scientists all over the world are focusing on exploiting the
      therapeutic potential of RNAi for identifying a new class of therapeutics. The
      applications of RNAi in medicine are unlimited because all cells possess RNAi
      machinery and hence all genes can be potential targets for therapy. RNAi can be
      developed as an endogenous host defense mechanism against many infections and
      diseases. Several studies have demonstrated therapeutic benefits of small
      interfering RNAs and micro RNAs in animal models. This has led to the rapid
      advancement of the technique from research discovery to clinical trials.

PMID- 18320565
TI  - Application of proteomics in biotechnology--microbial proteomics.
AB  - The genomes of most economically important microbial cells are already sequenced
      and proteomic technologies can be applied during various process development
      steps, starting with the selection and optimization of the functions of the
      industrial strains, application of the knowledge of cell function in response to
      the changes of production parameters, validation of the downstream processing,
      and thorough characterization of the final product. Unfortunately, there are only
      a few direct examples in the literature that present the optimization of the
      production process based on proteomics. In this review, we discuss the potential
      of this technology for the design of future bioprocesses and for optimization of
      existing ones.

PMID- 18320566
TI  - Identification of mouse heart transcriptomic network sensitive to various heart
      diseases.
AB  - Exploring biological systems from highly complex datasets is an important task
      for systems biology. The present study examined co-expression dynamics of mouse
      heart transcriptome by spectral graph clustering (SGC) to identify a heart
      transcriptomic network. SGC of microarray data produced 17 classified biological
      conditions (called condition spectrum, CS) and co-expression patterns by
      generating bi-clusters. The results showed dynamic co-expression patterns with a
      modular structure enriched in heart-related CS (CS-1 and -13) containing abundant
      heart-related microarray data. Consequently, a mouse heart transcriptomic network
      was constructed by clique analysis from the gene clusters exclusively present in
      the heart-related CS; 31 cliques were used for constructing the network. The
      participating genes in the network were closely associated with important cardiac
      functions (e. g., development, lipid and glycogen metabolisms). Online Mendelian
      Inheritance in Man (OMIM) database indicates that mutations of the genes in the
      network induced serious heart diseases. Many of the tested genes in the network
      showed significantly altered gene expression in an animal model of hypertrophy.
      The results suggest that the present approach is critical for constructing a
      heart-related transcriptomic network and for deducing important genes involved in
      the pathogenesis of various heart diseases.

PMID- 18320567
TI  - Glycoengineering of the methylotrophic yeast Hansenula polymorpha for the
      production of glycoproteins with trimannosyl core N-glycan by blocking core
      oligosaccharide assembly.
AB  - The initial lipid-linked oligosaccharide Glc(3)Man(9)GlcNAc(2)-dolichyl
      pyrophosphate (Dol-PP) for N-glycan is synthesized and assembled at the membrane
      of the endoplasmic reticulum (ER) and subsequently transferred to a nascent
      polypeptide by the oligosaccharide transferase complex. We have identified an
      ALG3 homolog (HpALG3) coding for a dolichyl-phosphate-mannose dependent alpha-1,3
      mannosyltransferase in the methylotrophic yeast Hansenula polymorpha. The
      detailed analysis of glycan structure by linkage-specific mannosidase digestion
      showed that HpALG3 is responsible for the conversion of Man5GlcNAc(2)-Dol-PP to
      Man(6)GlcNAc(2)-Dol-PP, the first step to attach a mannose to the lipid-linked
      oligosaccharide in the ER. The N-glycosylation pathway of H. polymorpha has been
      remodeled by deleting the HpALG3 gene in the Hpoch1 null mutant strain blocked in
      the yeast-specific outer mannose chain synthesis and by introducing an ER
      targeted Aspergillus saitoi alpha-1,2-mannosidase gene. This glycoengineered H.
      polymorpha strain produced glycoproteins mainly containing trimannosyl core N
      glycan (Man(3)GlcNAc(2)), which is the common core backbone of various human-type
      N-glycans. The results demonstrate the high potential of H. polymorpha to be
      developed as an efficient expression system for the production of glycoproteins
      with humanized glycans.

PMID- 18320568
TI  - A PCR-based strategy to generate yeast strains expressing endogenous levels of
      amino-terminal epitope-tagged proteins.
AB  - An epitope tag introduced to a gene of interest (GOI) greatly increases the ease
      of studying cellular proteins. Rapid PCR-based strategies for epitope tagging a
      protein's C-terminus at its native gene locus are widely used in yeast. C
      terminal epitope tagging is not suitable for all proteins, however. Epitope tags
      fused to the C-terminus can interfere with function of some proteins or can even
      be removed by C-terminal protein processing. To overcome such problems, proteins
      can be tagged with epitopes at their amino-termini, but generating yeast strains
      expressing N-terminal epitope tagged genes under control of the endogenous
      promoter at the native locus is comparatively more difficult. Strategies to
      introduce N-terminal epitope tags have been reported previously but often
      introduce additional sequences other than the epitope tag into the genome.
      Furthermore, N-terminal tagging of essential genes by current methods requires
      formation of diploid strains followed by tetrad dissection or expression of an
      additional copy of the GOI from a plasmid. The strategies described here provide
      a quick, facile means of epitope tagging the N-terminus of both essential and
      nonessential genes in a two-step PCR-based procedure. The procedure has the
      significant advantage of leaving tagged genes under the control of their
      endogenous promoters, and no additional sequences other than the epitope tag
      encoding nucleotides are inserted into the genome.

PMID- 18320569
TI  - Mining marine shellfish wastes for bioactive molecules: chitin and chitosan--Part
      B: applications.
AB  - Due to their unique chemical characteristics (including biodegradability to non
      toxic products, physiological inertness and hydrophilicity), chitin, chitosan and
      their derivatives may be expansively utilized in the biotechnological,
      agricultural, food protection and nutraceutical, medicinal and pharmacological
      fields and in the areas of bioremediation and gene therapy. Biological actions
      associated with chitin and shell waste by-products include among others
      antibacterial, angiotensin-1-converting enzyme-inhibitory and immunomodulatory
      activities, while the chitinolytic microbes and enzymes associated with
      chitinolysis also play a role in the de novo generation of further bioactivites.
      In Part B of this review we relate in more detail some of the bioactivities and
      applications of chitin and shell waste by-products.

PMID- 18320570
TI  - Physiological effects of thermally treated foods.

PMID- 18320571
TI  - Acrylamide in home-prepared roasted potatoes.
AB  - Potato is one of the world's most widely grown tuber crop, in which starch is the
      predominant form of carbohydrates. Potatoes can be prepared in many ways: boiled,
      fried or roasted. Frying and roasting potatoes at high temperatures result in an
      appetizing crust, but at the same time acrylamide can form. In this study, the
      concentrations of the acrylamide precursors, asparagine and sugars, were
      determined in five different Swedish-grown potato varieties, together with the
      acrylamide content after typical home-cooking procedures; oven-roasting of potato
      wedges and pan-frying of cubes of boiled potatoes. Pan-frying of boiled potato
      cubes resulted in higher levels of acrylamide (530-1100 microg/kg) than in the
      wedges (140-250 microg/kg). Blanching combined with a shorter roasting time was
      shown to be an efficient way of reducing the acrylamide content in roasted potato
      wedges, especially in the experiments performed after long-term storage, where
      the acrylamide content was reduced from 110-260 to 50-140 microg/kg. No
      correlation was found between precursor content and acrylamide content, and this
      finding emphasizes the need for further studies on factors affecting acrylamide
      formation, for example, the availability of precursors at the surface during
      cooking.

PMID- 18320572
TI  - A study on the use of empirical models to predict the formation of acrylamide in
      potato crisps.
AB  - The formation of acrylamide in potato crisps was fitted by empirical mathematical
      models. Potato slices were fried under the same experimental conditions for
      different times. Besides the content of precursors in the raw potato slices,
      acrylamide and water content in the potato crisps were quantified after
      predetermined times (2-6 min). The temperature developments in the surrounding
      oil and outer cell layer of the potato slices were monitored, giving more insight
      in the frying process and making future comparisons between studies possible. The
      pattern found for the formation of acrylamide, which was similar to earlier
      studies, was fitted to three empirical models. Statistical methods were used to
      compare the performance of the models, with the "Logistic-Exponential" and
      "Empirical" model performing equally well. The obtained model parameters were in
      the range of earlier reported studies, although this comparison is not
      unequivocal as the experimental conditions differed between studies. The
      precision of parameter estimates was problematic; this should be improved by
      better experimental design. Nevertheless, the approach of this study will make it
      possible to truly compare acrylamide formation patterns and model parameters in
      the future, with the ability to develop a tool to predict acrylamide formation in
      potato crisps.

PMID- 18320573
TI  - Binding of heterocyclic aromatic amines by lactic acid bacteria: results of a
      comprehensive screening trial.
AB  - Aim of the present study was a comprehensive investigation of the detoxification
      capacities of lactic acid bacteria (LAB) towards heterocyclic aromatic amines
      (HCA) formed during cooking of meat. It has been postulated that LAB prevent
      genotoxic and/or carcinogenic effects of HCA in laboratory rodents and humans via
      direct binding mechanisms. We measured the removal of the most abundant cooked
      food mutagens (AalphaC, PhIP, IQ, MeIQx, DiMeIQx) by eight LAB species. From each
      species, twelve strains were tested in liquid binding experiments with HPLC
      coupled with coulometric electrode array detection. The highest removal rates
      were observed with the representatives of the L. helveticus and S. thermophilus
      groups, which were seven to eight times more effective than L. kefir and L.
      plantarum. Strong and statistically significant differences were seen in the
      binding behaviour of the individual amines, the ranking order of detoxification
      being AalphaC > DiMeIQx > MeIQx > IQ > PhIP. Results of Salmonella/microsome
      assays with strain TA98 showed that the binding of AalphaC and PhIP to LAB
      correlates with the reduction of their mutagenic activities. This study may
      contribute to the development of strategies concerning the adverse health effects
      of HCA utilizing highly protective LAB for the production of fermented foods.

PMID- 18320574
TI  - N(epsilon)-carboxymethyllysine-modified proteins are unable to bind to RAGE and
      activate an inflammatory response.
AB  - Advanced glycation endproducts (AGEs) containing carboxymethyllysine (CML)
      modifications are generally thought to be ligands of the receptor for AGEs,
      RAGEs. It has been argued that this results in the activation of pro-inflammatory
      pathways and diseases. However, it has not been shown conclusively that a CML
      modified protein can interact directly with RAGE. Here, we have analyzed whether
      beta-lactoglobulin (bLG) or human serum albumin (HSA) modified chemically to
      contain only CML (10-40% lysine modification) can (i) interact with RAGE in vitro
      and (ii) interact with and activate RAGE in lung epithelial cells. Our results
      show that CML-modified bLG or HSA are unable to bind to RAGE in a cell-free assay
      system (Biacore). Furthermore, they are unable to activate pro-inflammatory
      signaling in the cellular system. Thus, CML probably does not form the necessary
      structure(s) to interact with RAGE and activate an inflammatory signaling cascade
      in RAGE-expressing cells.

PMID- 18320575
TI  - Protocatechuic acid: the missing human cyanidins' metabolite.

PMID- 18320577
TI  - High resolution microscopic survey of third metacarpal articular calcified
      cartilage and subchondral bone in the juvenile horse: possible implications in
      chondro-osseous disease.
AB  - The aim was to survey articular calcified cartilage (ACC) and subchondral bone in
      the palmar and dorsal regions of the condyles of the third metacarpal bone (Mc3)
      of young horses with minimal or no signs of musculo-skeletal abnormality. Back
      scattered electron scanning electron microscopy (BSE SEM) was conducted on
      polymethyl methacrylate-embedded mediolateral slices and macerated wedges of the
      right distal Mc3 from seven each of trained and untrained 2-year-old Thoroughbred
      horses. Furrows or grooves visible to the naked eye in the mineralizing front
      (MF) of ACC are the commonest "lesion" and are most common in the palmar portions
      of the medial and lateral condylar grooves. Cracks running predominantly in the
      parasagittal plane that infill with hypercalcified matrix are found in the same
      domain. Common to all these defects are deficiencies or absence of the ACC MF.
      Other anomalies include local excrescences or depressed areas of the MF. More
      important condylar lesions show displaced fragmented hypermineralized ACC with
      underlying excess resorption in the bone domain, leaving a thin ACC layer with
      cavernous space beneath it. The fragments may dislodge and displace to the joint
      space. Obvious although small lesions are present in horses that have undertaken
      little or no training. The nature and sites of the lesions indicate that they are
      possibly the earliest morphological evidence of changes that may lead to specific
      joint abnormalities. The lesions appear unlikely to be solely due to functional
      traumatic forces, and developmental influences are likely to be important in
      their initiation.

PMID- 18320578
TI  - A simple protocol for paraffin-embedded myelin sheath staining with osmium
      tetroxide for light microscope observation.
AB  - Experimental investigation of peripheral nerve fiber regeneration is attracting
      more and more attention among both basic and clinical researchers. Assessment of
      myelinated nerve fiber morphology is a pillar of peripheral nerve regeneration
      research. The gold standard for light microscopic imaging of myelinated nerve
      fibers is toluidine blue staining of resin-embedded semithin sections. However,
      many researchers are unaware that the dark staining of myelin sheaths typically
      produced by this procedure is due to osmium tetroxide postfixation and not due to
      toluidine blue. In this article, we describe a simple pre-embedding protocol for
      staining myelin sheaths in paraffin-embedded nerve specimens using osmium
      tetroxide. The method involves immersing the specimen in 2% osmium tetroxide for
      2 h after paraformaldehyde fixation, followed by routine dehydration and paraffin
      embedding. Sections can then be observed directly under the microscope or
      counterstained using routine histological methods. Particularly good results were
      obtained with Masson's trichrome counterstain, which permits the imaging of
      connective structures in nerves that are not detectable in toluidine blue-stained
      resin sections. Finally, we describe a simple protocol for osmium etching of
      sections, which makes further immunohistochemical analysis possible on the same
      specimens. Taken together, our results suggest that the protocol described in
      this article is a valid alternative to the conventional resin embedding-based
      protocol: it is much cheaper, can be adopted by any histological laboratory, and
      allows immunohistochemical analysis to be conducted.

PMID- 18320579
TI  - Reversible translocation of p115-RhoGEF by G(12/13)-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) are important targets for medicinal agents.
      Four different G protein families, G(s), G(i), G(q), and G(12), engage in their
      linkage to activation of receptor-specific signal transduction pathways. G(12)
      proteins were more recently studied, and upon activation by GPCRs they mediate
      activation of RhoGTPase guanine nucleotide exchange factors (RhoGEFs), which in
      turn activate the small GTPase RhoA. RhoA is involved in many cellular and
      physiological aspects, and a dysfunction of the G(12/13)-Rho pathway can lead to
      hypertension, cardiovascular diseases, stroke, impaired wound healing and immune
      cell functions, cancer progression and metastasis, or asthma. In this study,
      regulator of G protein signaling (RGS) domain-containing RhoGEFs were tagged with
      enhanced green fluorescent protein (EGFP) to detect their subcellular
      localization and translocation upon receptor activation. Constitutively active
      Galpha(12) and Galpha(13) mutants induced redistribution of these RhoGEFs from
      the cytosol to the plasma membrane. Furthermore, a pronounced and rapid
      translocation of p115-RhoGEF from the cytosol to the plasma membrane was observed
      upon activation of several G(12/13)-coupled GPCRs in a cell type-independent
      fashion. Plasma membrane translocation of p115-RhoGEF stimulated by a GPCR
      agonist could be completely and rapidly reversed by subsequent application of an
      antagonist for the respective GPCR, that is, p115-RhoGEF relocated back to the
      cytosol. The translocation of RhoGEF by G(12/13)-linked GPCRs can be quantified
      and therefore used for pharmacological studies of the pathway, and to discover
      active compounds in a G(12/13)-related disease context.

PMID- 18320580
TI  - Concerted actions of multiple transcription elements confer differential
      transactivation of HSP90 isoforms in geldanamycin-treated 9L rat gliosarcoma
      cells.
AB  - HSP90 chaperones are transducer proteins of many signaling pathways in cells.
      Using a highly specific inhibitor, geldanamycin (GA), an increasing number of the
      HSP90 client proteins have been identified. Nevertheless, there is little
      information on the differential transactivation of the two isoforms of the hsp90
      genes, hsp90alpha and beta, in cells under stress conditions. Here, we
      demonstrate the differential expression of the HSP90 isoforms, HSP90alpha and
      beta, in rat gliosarcoma 9L cells using a modified SDS-PAGE system that allowed
      us to distinguish the isoforms. We subsequently assessed the transcriptional
      controls involving the transcription elements located in the promoter regions of
      the hsp90 genes. At the protein level, HSP90alpha is more responsive to GA in
      terms of rate of de novo synthesis and amount of accumulation, as shown by
      metabolic-labeling and Western-blotting analyses. Upregulation of the hsp90 genes
      was demonstrated by real-time qPCR. The promoter elements hsp90alpha-HSE2 and
      hsp90beta-HSE1 were also identified to be the major transcription elements
      involved in GA-activated gene expression, as shown by EMSA, whereas the results
      of supershift showed that the transcription factor HSF1 is also involved.
      Moreover, EMSA results of analysis of the GC box showed differences in both the
      initial amounts and inductive response of hsp90s transcripts, whereas analysis of
      the TATA box showed GA responsiveness in hsp90alpha only. Collectively, these
      results indicate that GA exerts its regulatory effects through transcription
      elements including heat-shock elements (HSEs), GC boxes and TATA boxes, resulting
      in differential transactivation of hsp90alpha and hsp90beta in rat gliosarcoma 9L
      cells.

PMID- 18320581
TI  - Work injuries among drivers in the goods-transport branch in Denmark.
AB  - BACKGROUND: Goods-transport drivers in Denmark had an elevated rate of hospital
      contact due to injury compared with the skilled/semiskilled workforce in general
      in recent years. There is a need to elucidate the causes of their work injuries.
      METHODS: We analyzed the Danish National Work Injury Register for the 10-year
      period 1993-2002. RESULTS: The vast majority (92.6%) of the work injuries among
      goods-transport were sustained under non-traffic activities, that is, collecting,
      loading, unloading, and delivering goods. They fell from height (22.3%), suffered
      from overexertion (14.2%), got caught between/under objects (12.6%), collided
      with objects (12.0%), slipped/tripped (10.6%), or got struck by falling objects
      (9.0%). CONCLUSIONS: There is a clear need for efforts to prevent work injuries
      under non-traffic activities among goods-transport drivers in Denmark. For this
      end, it is necessary to involve not only the drivers' employers for reinforcement
      of safety procedures, but also the employers' customers for improvement of the
      physical environment, in which drivers collect, load, unload, and deliver goods.

PMID- 18320582
TI  - Surveillance of musculoskeletal injuries and disorders in a diverse cohort of
      workers at a tertiary care medical center.
AB  - BACKGROUND: The purpose of this study was to investigate the incidence of work
      related musculoskeletal (MSK) injuries and disorders among a dynamic cohort of
      health care workers, including direct care providers and support services,
      employed at a tertiary care medical center. METHODS: Human resources data were
      used to define the cohort and time at risk. Workers' compensation (WC) records
      (1997-2003) were utilized to identify work-related MSK claims. Poisson regression
      was used to generate gender specific rate ratios and 95% confidence intervals
      (CI) of MSK injuries among workgroups. RESULTS: MSK injuries resulted equally (
      approximately 30% each) from lift/push/pull of equipment, patient handling, and
      slip/trip/falls. Injury rates and their mechanisms varied substantially by
      occupational group, gender, and race. Even with declining injury rates over time,
      black workers had rates 2.5 times higher than other workers and women had rates
      1.8 times higher than men. Male and female nurses' aides, housekeepers, and
      radiology technicians had among the highest rates of injury, while lost workdays
      rates were highest for male and female nurses' aides, female housekeepers, and
      male patient transporters. CONCLUSIONS: Differential risk associated with work
      tasks in highly segregated work populations can contribute to disparities in
      health, and the patterns we observed partly reflect the high concentration of
      female and black workers in occupations with increased physical demands. While
      the greatest public health impact will be achieved by implementing prevention
      strategies among large workgroups with high injury rates, public health efforts
      must not ignore smaller, often segregated, workgroups identified in this study as
      high risk.

PMID- 18320583
TI  - Phenotypic variations of TRAIL sensitivity in cloned populations of prostate
      cancer cells.
AB  - Factors that regulate the induction of apoptosis of tumour cells are potential
      candidates for therapeutic intervention for the majority of cancers. Studying
      modifiers of apoptotic responses, such as members of the tumour necrosis factor
      receptor superfamily, may give clues as to how induction of apoptosis in tumours
      could be maximized to enhance the benefit of treatment regimes. Tumour necrosis
      factor-related apoptosis-inducing ligand (TRAIL) is a promising anti-tumour
      molecule since its activity is specific for tumour cell populations. TRAIL binds
      to death receptors, inducing apoptosis in susceptible cells. The mechanisms which
      determine whether tumour cells are susceptible to TRAIL are unclear, and several
      mechanisms have been proposed, including expression of osteoprotegerin (OPG),
      decoy receptors, and factors that affect intracellular signalling of pro
      apoptotic molecules, such as c-FLIP. Here we show that experiments to modulate
      the activity of one of these factors, OPG, by over-expression and also by stable
      knockdown of OPG expression, alters the TRAIL sensitivity of PC3 prostate cancer
      cells. However we show that some observed effects, which appear to support the
      hypothesis that OPG prevents TRAIL-induced apoptosis of tumour cells, may be due
      to variation of the TRAIL response of sub-clones of tumour cells, even within a
      cloned population. These results highlight potential limitations of experiments
      designed to test contribution of factors affecting intrinsic apoptosis
      susceptibility using cloned tumour cell populations.

PMID- 18320584
TI  - Effects of external interactions on protein sequence-structure relations of beta
      trefoil fold.
AB  - Proteins with symmetric structures are ideal models to investigate the sequence
      structure relations. We investigate proteins with beta-trefoil fold and find they
      have different degrees of sequence symmetries although they show similar
      symmetric structures. To understand this, we calculate the strength of
      interactions of the beta-trefoil folds with surrounding environments and find the
      low degrees of sequence symmetries are often correlated with large external
      interactions. Our results give an additional confirmation of Anfinsen's
      thermodynamic hypothesis that protein structures are not only determined by their
      sequences but also by their surrounding environments. We suggest the external
      interactions should be considered additionally in protein structure prediction
      through ab initio folding.

PMID- 18320585
TI  - Identification of proteins interacting with protein arginine methyltransferase 8:
      the Ewing sarcoma (EWS) protein binds independent of its methylation state.
AB  - Protein arginine methylation is a eukaryotic posttranslational modification that
      plays a role in transcription, mRNA splicing and transport, in protein-protein
      interaction, and cell signaling. The type I protein arginine methyltransferase
      (PRMT) 8 is the only member of the human PRMT family that is localized at the
      cell membrane and its endogenous substrates have remained unknown as yet.
      Although PRMT8 was supposed to be expressed only in brain tissue, its presence in
      HEK 293 (T) cells could be demonstrated. We identified more than 20 PRMT8-binding
      partners in pull-down experiments using recombinant PRMT8 as bait followed by
      mass spectrometric identification of the bound proteins. Among the extracted
      proteins were several heterogeneous nuclear ribonucleoproteins (hnRNP), RNA
      helicases (DEAD box proteins), the TET-family proteins TLS, Ewing's sarcoma
      (EWS), and TAF(II)68, and caprin, which all contain RGG methylation motifs and
      are potential substrates of PRMT8. Additionally, actin, tubulin, and heat shock
      proteins belong to the identified proteins. The interaction between PRMT8 and the
      EWS protein was characterized in more detail. Although binding of endogenous and
      recombinant EWS protein to PRMT8 as well as colocalization in HEK cells was
      observed, in vitro methylation assays revealed a rather poor methyltransferase
      activity of PRMT8 towards the EWS protein and a synthetic RGG-rich reference
      peptide (K(m), 1.3 microM; k(cat)/K(m), 2.8 x 10(-4) microM(-1) s(-1)) in
      comparison to PRMT1 (K(m), 0.8 microM; k(cat)/K(m), 8.1 x 10(-3) microM(-1) s(
      1)). In contrast, substrate proteins within a cell extract could be methylated by
      PRMT8 as efficient as by PRMT1. The main interaction site of the EWS protein with
      PRMT8 was determined to be the C-terminal RGG box 3. Remarkably, complete
      methylation of the EWS protein did not abrogate the binding to PRMT8, pointing to
      an adapter role of PRMT8 for nuclear proteins at the cell membrane in addition to
      its methyltransferase activity.

PMID- 18320586
TI  - Scan2S: increasing the precision of PROSITE pattern motifs using secondary
      structure constraints.
AB  - Sequence signature databases such as PROSITE, which include protein pattern
      motifs indicative of a protein's function, are widely used for function
      prediction studies, cellular localization annotation, and sequence
      classification. Correct annotation relies on high precision of the motifs. We
      present a new and general approach for increasing the precision of established
      protein pattern motifs by including secondary structure constraints (SSCs). We
      use Scan2S, the first sequence motif-scanning program to optionally include SSCs,
      to augment PROSITE pattern motifs. The constraints were derived from either the
      DSSP secondary structure assignment or the PSIPRED predictions for PROSITE
      documented true positive hits. The secondary structure-augmented motifs were
      scanned against all SwissProt sequences, for which secondary structure
      predictions were precalculated. Against this dataset, motifs with PSIPRED-derived
      SSCs exhibited improved performance over motifs with DSSP-derived constraints.
      The precision of 763 of the 782 PSIPRED-augmented motifs remained unchanged or
      increased compared to the original motifs; 26 motifs showed an absolute precision
      increase of 10-30%. We provide the complete set of augmented motifs and the
      Scan2S program at http://physiology.med.cornell.edu/go/scan2s. Our results
      suggest a general protocol for increasing the precision of protein pattern
      detection via the inclusion of SSCs.

PMID- 18320587
TI  - Enzymatic characterization and crystal structure analysis of the D-alanine-D
      alanine ligase from Helicobacter pylori.
AB  - D-Alanine-D-alanine ligase is the second enzyme in the D-Ala branch of bacterial
      cell wall peptidoglycan assembly, and recognized as an attractive antimicrobial
      target. In this work, the D-Ala-D-Ala ligase of Helicobacter pylori strain SS1
      (HpDdl) was kinetically and structurally characterized. The determined apparent
      K(m) of ATP (0.87 microM), the K(m1) (1.89 mM) and K(m2) of D-Ala (627 mM), and
      the k(cat) (115 min(-1)) at pH 8.0 indicated its relatively weak binding affinity
      and poor catalytic activity against the substrate D-Ala in vitro. However, by
      complementary assay of expressing HpDdl in Escherichia coli Delta ddl mutant,
      HpDdl was confirmed to be capable of D-Ala-D-Ala ligating in vivo. Through
      sequence alignment with other members of the D-Ala-D-X ligase superfamily, HpDdl
      keeps two conservatively substituted residues (Ile16 and Leu241) and two
      nonconserved residues (Leu308 and Tyr311) broadly located in the active region of
      the enzyme. Kinetic analyses against the corresponding HpDdl mutants (I16V,
      L241Y, L241F, L308T, and Y311S) suggested that these residues, especially Leu308
      and Tyr311, might partly contribute to the unique catalytic properties of the
      enzyme. This was fairly proved by the crystal structure of HpDdl, which revealed
      that there is a 3(10)-helix (including residues from Gly306 to Leu312) near the D
      Ala binding region in the C-terminal domain, where HpDdl has two sequence
      deletions compared with other homologs. Such 3(10)-helix may participate in D-Ala
      binding and conformational change of the enzyme. Our present work hopefully
      provides useful information for understanding the D-Ala-D-Ala ligase of
      Helicobacter pylori.

PMID- 18320588
TI  - Crystal structure of the C-terminal conserved domain of human GRP, a galectin
      related protein, reveals a function mode different from those of galectins.

PMID- 18320589
TI  - Calcineurin B-like domains in the large regulatory alpha/beta subunits of
      phosphorylase kinase.
AB  - Phosphorylase kinase (PhK) is a large hexadecameric complex that catalyzes the
      phosphorylation and activation of glycogen phosphorylase (GP). It consists in
      four copies each of a catalytic subunit (gamma) and three regulatory subunits
      (alpha beta delta). Delta corresponds to endogenous calmodulin, whereas little is
      known on the molecular architecture of the large alpha and beta subunits, which
      probably arose from gene duplication. Here, using sensitive methods of sequence
      analysis, we show that the C-terminal domain (named domain D) of these alpha and
      beta subunits can be significantly related to calcineurin B-like (CBL) proteins.
      CBL are members of the EF-hand family that are involved in the regulation of
      plant-specific kinases of the CIPK/PKS family, and relieve autoinhibition of
      their target kinases by binding to their regulatory region. The relationship
      highlighted here suggests that PhK alpha and/or beta domain D may be involved in
      a similar regulation mechanism, a hypothesis which is supported by the
      experimental observation of a direct interaction between domain D of PhKalpha and
      the regulatory region of the Gamma subunit. This finding, together the
      identification of significant similarities of domain D with the preceding domain
      C, may help to understand the molecular mechanism by which PhK alpha and/or beta
      domain D might regulate PhK activity.

PMID- 18320590
TI  - Structure-based prediction of transcription factor binding sites using a protein
      DNA docking approach.
AB  - Accurate identification of transcription factor binding sites is critical to our
      understanding of transcriptional regulatory networks. To overcome the issue of
      high false-positive predictions that trouble the sequence-based prediction
      techniques, we have developed a structure-based prediction method that takes into
      consideration of interactions between the amino acids of a transcription factor
      and the nucleotides of its DNA binding sequence at structural level, along with
      an efficient protein-DNA docking algorithm. The docked structures between a
      protein and a DNA are evaluated using a knowledge-based energy function, in
      conjunction with van der Waals energy. Our docking algorithm supports quasi
      flexible docking, overcoming a number of limiting issues faced by similar docking
      algorithms. Our rigid-body docking algorithm is tested on a dataset of 141
      nonredundant transcription factor-DNA complex structures. The test results show
      that 63.1% of the 141 complex structures are reconstructed with accuracies better
      than 1.0 A RMSDs (root mean square deviation) and 79.4% of the complexes are
      predicted with accuracies better than 3.0 A RMSDs when using the native DNA
      structures. Our quasi-flexible docking algorithm, assuming that the DNA
      structures are not known, is tested on a separate set of 45 transcription factor
      DNA complexes, of which 57.8% of the docked complex conformations achieve better
      than 1.0 A RMSDs while 71.1% of the complexes have RMSDs less than 3.0 A. We have
      also applied our method to predict the binding motifs of the ferric uptake
      regulator in E. coli and showed that most of the experimentally identified sites
      can be predicted accurately.

PMID- 18320591
TI  - All-atom replica exchange molecular simulation of protein BBL.
AB  - Downhill folding is one of the most important predictions of energy landscape
      theory. Recently, the Escherichia coli 2-oxoglutarate dehydrogenase PSBD was
      described as a first example of global downhill folding (Garcia-Mira et al.,
      Science 2002;298:2191), classification that has been later subject of significant
      controversy. To help resolve this problem, by using intensive all-atom simulation
      with explicit water model and the replica exchange method, we sample the phase
      space of protein BBL and depict the free energy landscape. We give an estimate of
      the free energy barrier height of 1-2 k(B)T, dependent on the way the energy
      landscape is projected. We also study the conformational distribution of the
      transition region and find that the three helices generally take the similar
      positions as that in the native states whereas their spatial orientations show
      large variability. We further detect the inconsistency between different signals
      by individually fitting the thermal denaturation curves of five structural
      features using two-state model, which gives a wide spread melting temperature of
      19 K. All of these features are consistent with a picture of folding with very
      low cooperativities. Compared with the experimental data (Sadqi et al., Nature
      2006; 442:317), our results indicate that the Naf-BBL (pH5.3) may have an even
      lower barrier height and cooperativity.

PMID- 18320592
TI  - Proteomic identification of malignant transformation-related proteins in
      esophageal squamous cell carcinoma.
AB  - Esophageal cancer (EC) persists to be a leading cancer-related death in northern
      China. Clinical outcome of EC is the most dismal among many types of digestive
      tumors because EC at early stage is asymptomatic. The current study used 2-DE
      based proteomics to identify differentially expressed proteins between esophageal
      cancer cell lines and immortal cell line. Fifteen proteins were identified with
      differences of more than five folds, comprising the down-regulation of annexin
      A2, histone deacetylase 10 isoform beta and protein disulfide-isomerase ER-60
      precursor, and the up-regulation of heat shock 70 kDa protein 9B precursor,
      solute carrier family 44 Member 3, heterogeneous nuclear ribonucleoprotein L
      (hnRNP L), eukaryotic translation initiation factor 4A isoform 2, triosephosphate
      isomerase1 (TPI), peroxiredoxin1 (PRX1), forminotransferase cyclodeaminase form
      (FTCD), fibrinogen gamma-A chain precursor, kinesin-like DNA binding protein,
      lamin A/C, cyclophilin A (CypA), and transcription factor MTSG1. Expression
      pattern of annexin A2 was verified by Western blotting, immunocytochemistry and
      immunohistochemistry analysis. The implication of these protein alterations
      correlated to the esophageal malignant transformation is discussed.

PMID- 18320593
TI  - 5alpha-androstane-3alpha,17beta-diol supports human prostate cancer cell survival
      and proliferation through androgen receptor-independent signaling pathways:
      implication of androgen-independent prostate cancer progression.
AB  - Androgen and androgen receptor (AR) are involved in growth of normal prostate and
      development of prostatic diseases including prostate cancer. Androgen deprivation
      therapy is used for treating advanced prostate cancer. This therapeutic approach
      focuses on suppressing the accumulation of potent androgens, testosterone and
      5alpha-dihydrotestosterone (5alpha-DHT), or inactivating the AR. Unfortunately,
      the majority of patients with prostate cancer eventually advance to androgen
      independent states and no longer respond to the therapy. In addition to the
      potent androgens, 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), reduced
      from 5alpha-DHT through 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs),
      activated signaling may represent a novel pathway responsible for the progression
      to androgen-independent prostate cancer. Androgen sensitive human prostate cancer
      LNCaP cells were used to compare 5alpha-DHT and 3alpha-diol activated androgenic
      effects. In contrast to 5alpha-DHT, 3alpha-diol regulated unique patterns of beta
      catenin and Akt expression as well as Akt phosphorylation in parental and in AR
      silenced LNCaP cells. More significantly, 3alpha-diol, but not 5alpha-DHT,
      supported AR-silenced LNCaP cells and AR negative prostate cancer PC-3 cell
      proliferation. 3alpha-diol-activated androgenic effects in prostate cells cannot
      be attributed to the accumulation of 5alpha-DHT, since 5alpha-DHT formation was
      not detected following 3alpha-diol administration. Potential accumulation of
      3alpha-diol, as a result of elevated 3alpha-HSD expression in cancerous prostate,
      may continue to support prostate cancer growth in the presence of androgen
      deprivation. Future therapeutic strategies for treating advanced prostate cancer
      might need to target reductive 3alpha-HSD to block intraprostatic 3alpha-diol
      accumulation.

PMID- 18320594
TI  - Associations between patella lead and blood pressure in lead workers.
AB  - BACKGROUND: To compare associations of patella lead, a lead pool that may capture
      aspects of both current bioavailable and cumulative lead dose thus offering
      advantages over tibia or blood lead, with blood lead in models of blood pressure
      and hypertension and to examine effect modification by age, sex and polymorphisms
      of the genes encoding for the vitamin D receptor (VDR) and delta-aminolevulinic
      acid dehydratase (ALAD). METHODS: Cross-sectional data in 652 current and former
      lead workers were analyzed. RESULTS: Blood lead, but not patella lead, was
      positively associated with systolic blood pressure. Neither lead measure was
      associated with diastolic blood pressure or hypertension status. There was no
      evidence of effect modification. CONCLUSIONS: In these workers, blood lead was
      more relevant to elevations in blood pressure than was patella lead. Additional
      research will be required to determine whether patella lead assessment provides
      unique information on vascular risk from lead exposure.

PMID- 18320595
TI  - Electron ionization time-of-flight mass spectrometry: historical review and
      current applications.
AB  - This review presents an overview of electron ionization time-of-flight mass
      spectroscopy (EITOFMS), beginning with its early development to the employment of
      modern high-resolution electron ionization sources. The EITOFMS is demonstrated
      to be ideally suited for analytical and basic chemical physics studies. Studies
      of the formation of positive ions by electron ionization time-of-flight mass
      spectroscopy have been responsible for many of the known ionization potentials of
      molecules and radicals, as well as accepted bond dissociation energies for ions
      and neutral molecules. The application of TOFMS has been particularly important
      in the area of negative ion physics and chemistry. A wide variety of negative ion
      properties have been discovered and studied by using these methods including:
      autodetachment lifetimes, metastable dissociation, Rydberg electron transfer
      reactions and field detachment, SF(6) Scavenger method for detecting temporary
      negative ion states, and many others.

PMID- 18320596
TI  - Integration of hepatitis B virus DNA into the myeloid/lymphoid or mixed-lineage
      leukemia (MLL4) gene and rearrangements of MLL4 in human hepatocellular
      carcinoma.
AB  - Integration of hepatitis B virus (HBV) DNA into host DNA is detected in about 90%
      of HBV-related hepatocellular carcinoma (HCC), but the preferential sites of the
      viral integration etiologically relevant to oncogenesis have been controversial.
      By using an adaptor-ligation/suppression-PCR, we identified four integrations
      into the myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4) gene from 10 HCC
      patients with positive HBV surface antigen (HBsAg). Determination of the cellular
      virus DNA junction demonstrated that various lengths of the virus were integrated
      within 300 bp of intron 3 flanked by the Alu element of MLL4. Chimeric hepatitis
      B virus X gene (HBx)/MLL4 transcripts and the HBx fusion proteins were detected.
      DNA microarray revealed that HBx/MLL4 fusion proteins suppressed unique genes in
      HepG2 cells. Finally, chromosomal translocations of intron 3 of MLL4 to the
      specific region of chromosome 17p11.2 in 22 out of 32 HCC patients were observed,
      showing that the intron 3 region of MLL4 gene would be a target of translocation
      breakpoint. In conclusion, the present data suggest that the translocation
      breakpoint of MLL4 gene is one of the preferential targets for HBV DNA
      integration into the MLL4 gene and the HBV DNA integration may be involved in
      liver oncogenesis.

PMID- 18320598
TI  - Dip Pen Nanolithography: a "Desktop Nanofab" approach using high-throughput
      flexible nanopatterning.
AB  - The ability to perform controllable nanopatterning with a broad range of "inks"
      at ambient conditions is a key aspect of the dip pen nanolithography (DPN)
      technique. The traditional ink system to demonstrate DPN is n-alkanethiols on a
      gold substrate, but the DPN method has found numerous other applications since.
      This article is meant to outline recent advances in the DPN toolkit, both in
      terms of research and patterning technology, and to discuss applications of DPN
      as a viable nanofabrication method. We will summarize new DPN developments, and
      introduce our concept of the "Desktop Nanofab." In addition, we outline our
      efforts to commercialize DPN as a viable nanofabrication technique by
      demonstrating massively parallel nanopatterning with the 55,000 tip 2D nano
      PrintArray. This demonstrates our ability to overcome the serial nature of DPN
      patterning and enable high-throughput nanofabrication.

PMID- 18320599
TI  - Dynamic variations in adhesion of self-assembled monolayers on nanoasperities
      probed by atomic force microscopy.
AB  - Octadecyltriethoxysilane (OTE) self- assembled monolayers (SAMs) and their
      effects on friction and adhesion have been investigated on various combinations
      of functionalized and unfunctionalized silicon oxide surfaces including the
      oxidized surface of crystalline Si(100), silica nanoparticle films, and oxidized
      Si atomic force microscopy (AFM) tips. Force-distance spectroscopy was utilized
      to probe and compare the properties of the OTE SAMs on silica asperities with
      nanoscale curvature against these same monolayers on surfaces with sub-1 nm
      roughness (flat surfaces). It was found that adhesion between SAMs and silicon
      oxide surfaces can vary significantly when assembly takes place on surfaces with
      nanoscopic curvature as compared to flat surfaces. Observations indicate that the
      SAM structure present during force measurements is dynamic in nature, which
      yields different adhesion values when measured with variations of both tip-sample
      contact time and tip-approach/retract rates. These results point the need in
      reporting a number of measurement parameters when probing adhesion by SAM
      functionalized tips.

PMID- 18320600
TI  - Morphology and amine accessibility of (3-aminopropyl) triethoxysilane films on
      glass surfaces.
AB  - 3-Aminopropyl) triethoxysilane (APTES) is commonly used to functionalize glass
      substrates because it can form an amine-reactive film that is tightly attached to
      the surface. In this study, we investigated the morphology and chemical
      reactivity of APTES films prepared on glass substrates using common deposition
      techniques. Films were prepared using concentrated vapor-phase deposition, dilute
      vapor-phase deposition, anhydrous organic-phase deposition and aqueous-phase
      deposition. All films were annealed, or cured, at 150 degrees C. The morphology
      of the films was quantified by fluorescence and by atomic force microscopy (AFM).
      The optical equivalent of the AFM images was computed and then used to directly
      compare optical and AFM images. Reactive amine density was determined by a picric
      acid assay and by a method that employed N-succinimidyl 3-[2-pyridyldithio]
      propionamido (SPDP) cross-linked rhodamine. Fluorescence and AFM images showed
      that silane films prepared from dilute vapor-phase and aqueous-phase deposition
      were more uniform and had fewer domains than those deposited by the other
      methods. The ratio of picric acid-accessible amino groups to SPDP cross-linked
      rhodamine-accessible groups varied with the preparation method, suggesting
      reactant size-dependent difference in amine accessibility. We found a larger
      number of accessible amino groups on films prepared by vapor-phase deposition
      than on those prepared from solution deposition. The dilute vapor-phase
      deposition technique produced relatively few domains, and it should be a good
      choice for bioconjugation applications. There were appreciable differences in the
      films produced by each method. We suggest that these differences originate from
      differences in film rearrangement during annealing.

PMID- 18320601
TI  - Systematic review of statistical methods used in molecular marker studies in
      cancer.
AB  - BACKGROUND: There is wide interest in the use of molecular markers for the early
      detection of cancer, the prediction of disease outcome, and the selection of
      patients for chemotherapy. Despite significant and increasing research activity,
      to the authors' knowledge only a small number of molecular markers have been
      successfully integrated into clinical practice. In the current study, the
      experimental designs and statistical methods used in contemporary molecular
      marker studies are reviewed, particularly with respect to whether these evaluated
      a marker's clinical value. METHODS: MEDLINE was searched for studies that
      analyzed an association between a cancer outcome and a marker involving chemical
      analysis of body fluid or tissue. For each article, data were extracted regarding
      patients, markers, type of statistical analysis, and principal results. RESULTS:
      The 129 articles eligible for analysis included a very large variety of molecular
      markers; the total number of markers was larger than the number of articles. Only
      a minority of articles (47 articles; 36%) incorporated multivariate modeling in
      which the marker was added to standard clinical variables, and only a very small
      minority had any measure of predictive accuracy (14 articles; 11%). No article
      used decision analytic methods or experimentally evaluated the clinical value of
      a marker. Correction for overfit was also rare (3 articles). CONCLUSIONS:
      Statistical methods in molecular marker research have not focused on the clinical
      value of a marker. Attention to sound statistical practice, in particular the use
      of statistical approaches that provide clinically relevant information, will help
      maximize the promise of molecular markers for care of the cancer patient.

PMID- 18320602
TI  - Adjuvant high-dose interferon for cutaneous melanoma is most beneficial for
      patients with early stage III disease.
AB  - BACKGROUND: Evidence from randomized trials in the pre-sentinel lymph node biopsy
      era indicate that adjuvant treatment with high-dose interferon-alpha (IFN)
      increases recurrence-free survival (RFS) in patients with high-risk melanoma.
      However, to the authors' knowledge, the role of this treatment in selected
      patients with early stage III disease has not been well studied. METHODS: The
      clinical and pathologic characteristics of 486 patients undergoing surgical
      treatment for stage III melanoma were evaluated and the authors compared outcomes
      for those given adjuvant treatment with IFN with those patients who had surgery
      alone. A particular focus was on the effect of IFN therapy on RFS and overall
      survival (OS) among those patients with stage IIIA disease. RESULTS: The median
      follow-up for the entire cohort was 5.2 years; the 5-year RFS and OS rates for
      the entire group were 41% and 53%, respectively. Adjuvant IFN was given to 141
      patients (29%). On multivariate analysis, IFN was found to be the only
      independent predictor for RFS in patients with stage IIIA disease (hazards ratio
      of 0.4; 95% confidence interval, 0.2-0.9 [P = .02]). IFN was not found to be
      associated with increased RFS in patients with more advanced lymph node disease
      (stage IIIB and stage IIIC). IFN appeared to have no effect on OS in any patient
      with stage III disease. CONCLUSIONS: Adjuvant treatment with IFN improves RFS in
      melanoma patients with early stage III disease. The results of the current study
      should help guide management when considering adjuvant treatment for these
      patients.

PMID- 18320603
TI  - On the time-course and frequency selectivity of the EEG for different modes of
      response selection: evidence from speech production and keyboard pressing.
AB  - OBJECTIVE: To compare brain activity in the alpha and beta bands in relation to
      different modes of response selection, and to assess the domain generality of the
      response selection mechanism using verbal and non-verbal tasks. METHODS: We
      examined alpha and beta event-related desynchronization (ERD) to analyze brain
      reactivity during the selection of verbal (word production) and non-verbal motor
      actions (keyboard pressing) under two different response modes: externally
      selected and self-selected. RESULTS: An alpha and beta ERD was observed for both
      the verbal and non-verbal tasks in both the externally and the self-selected
      modes. For both tasks, the beta ERD started earlier and was longer in the self
      selected mode than in the externally selected mode. The overall pattern of
      results between the verbal and non-verbal motor behaviors was similar.
      CONCLUSIONS: The pattern of alpha and beta ERD is affected by the mode of
      response selection suggesting that the activity in both frequency bands
      contributes to the process of selecting actions. We suggest that activity in the
      alpha band may reflect attentional processes while activity in the beta band may
      be more closely related to the execution and selection process. SIGNIFICANCE:
      These results suggest that a domain general process contributes to the planning
      of speech and other motor actions. This finding has potential clinical
      implications, for the use of diverse motor tasks to treat disorders of motor
      planning.

PMID- 18320604
TI  - Event-related potentials to pitch and rise time change in children with reading
      disabilities and typically reading children.
AB  - OBJECTIVE: The purpose of the present study was to investigate whether children
      with reading disabilities (RD) process rise time and pitch changes differently to
      control children as a function of the interval between two tones. METHODS:
      Children participated in passive oddball event-related potential (ERP)
      measurements using paired stimuli. Mismatch negativity (MMN), P3a and late
      discriminative negativity (LDN) responses to rise time and pitch changes were
      examined. RESULTS: Control children produced larger responses than children with
      RD to pitch change in the P3a component but only when the sounds in the pair were
      close to each other. Compared to children with RD, MMN was smaller and LDN larger
      in control children in response to rise time change when the sounds in the pair
      were further apart. The non-overlap in ERP measures between the groups was 40
      50%. CONCLUSIONS: Problems in rapid processing of pitch change were reflected in
      a component associated with attention switching while amplitude envelope
      processing problems were reflected in components associated with stimulus
      detection or discrimination. SIGNIFICANCE: Children with RD process both rise
      time and pitch changes differently from control children thus providing evidence
      for the nature of amplitude envelope processing and rapid auditory processing
      deficits in dyslexia.

PMID- 18320605
TI  - Chromatographic alignment improves differential MS.

PMID- 18320606
TI  - Applying rapid genome sequencing technologies to characterize pathogen genomes.

PMID- 18320607
TI  - Environmental chemis-tree reveals contamination. Trees pinpoint toxic pollution
      sites.

PMID- 18320608
TI  - Abstract withdrawal.

PMID- 18320609
TI  - Patient satisfaction with different asthma-training variants.
AB  - OBJECTIVE: Information on patient satisfaction with professional health care
      delivery in asthmatics is rare, and the question as to how asthma education
      programmes affect such satisfaction has not yet been addressed. METHODS: This
      multi-centre study investigated three different variants of an asthma education
      programme for adults. Patients participated either in variant B (basic training
      with teacher-directed presentation, two 90 min sessions), variant C
      (comprehensive training, four sessions), variant D (including additional
      psychological components, minimum five sessions), or variant E (equivalent to B
      in outpatient context). At the end of the training the perceived satisfaction
      with the programme and reported personal benefit were assessed by means of a new
      inventory that was developed. RESULTS: The sample comprised N = 320 patients (n =
      244 inpatients and n = 76 outpatients) ranging in age from 18 to 80 years (M =
      46.3 years). The average total score for educational satisfaction of all
      participants was 8.0 (maximum score = 10). Choice of topics was judged
      particularly positive (M = 8.58), followed by the structure of training/setting
      conditions (M = 8.0). The perceived personal benefit from the training was
      evaluated less positively (M = 7.32). When comparing the programme variants,
      patients' average satisfaction tends to increase with the extent and intensity of
      the training offered. Outpatients showed significantly less satisfaction in
      contrast to inpatients. Inpatients' satisfaction with the three variants
      increased with extensiveness and intensity of the training, while the contrast of
      between-group comparisons (B-C, B-D and C-D) was significant. CONCLUSION:
      Assessment of the patient's view of health care services should complement
      standardised evaluation methods, especially in multi-intervention rehabilitation
      programmes. PRACTICE IMPLICATIONS: Rehabilitation-specific diagnostic measures
      should be developed and validated in order to better assess patients'
      satisfaction and training efficacy from the patient's perspective. Further study
      is recommended on how far individualised training measures might increase
      subjective benefit.

PMID- 18320610
TI  - Biomimetic nitration of the linoleic acid metabolite 13-hydroxyoctadecadienoic
      acid: isolation and spectral characterization of novel chain-rearranged epoxy
      nitro derivatives.
AB  - Nitration of unsaturated fatty acids is a (patho)physiologically important
      pathway of lipid modification induced by nitric oxide-derived species. We report
      herein on the unexpected chain rearrangement undergone by (13S,9Z,11E)-13
      hydroxyoctadeca-9,11-dienoic acid (1), a linoleic acid metabolite, when exposed
      to nitrating agents of biological relevance. At pH 7.4 and at room temperature,
      reaction of 1 with peroxynitrite (ONOO-) as well as Fe2+-EDTA/H2O2/NO2- and
      horseradish peroxidase/H2O2/NO2- led to the formation of two nitration products,
      which could be isolated as the methyl esters and were identified as
      diastereoisomeric methyl (12S)-10,11-epoxy-12-hydroxy-9
      nitromethylheptadecanoates by extensive 1H, 13C, 15N NMR and MS analysis.

PMID- 18320611
TI  - Effect of the immunosuppressants on hepatocyte cells proliferation and apoptosis
      during liver regeneration after hepatectomy - molecular studies.
AB  - The regeneration and remodeling of the transplanted liver is the result of
      hepatocyte proliferation and apoptosis (programmed cell death). The purpose of
      this study was to verify the influence of immunosuppressants on the expression
      levels of genes: IL-6 (regulator of hepatocyte proliferation), pro-apoptotic (Bak
      and Bax) and anti-apoptotic (Bcl-Xl and Bcl-2). 36 newborn suckling rats (age 5-7
      days, weight 6-10 g) were divided into four groups: hepatectomy, hepatectomy plus
      methylprednisolone, hepatectomy plus CsA and hepatectomy plus Tac. The same
      experiments were performed in 24 weaning rats (age 21-23 days, weight 30-50 g).
      The animals were killed one day after the hepatectomy and the remnant livers were
      analyzed. The livers of all animals exhibited histological changes of liver
      regeneration. The immunosuppressants did not promote any alteration on IL-6 gene
      expression levels. Methylprednisolone and CsA increased the expression levels of
      Bak gene in newborn rats. However, methylprednisolone and Tac promoted increased
      expression levels of Bcl-2 in all groups. We hypothesize that these effects
      explain the efficacy of these drugs on the treatment of acute and chronic liver
      rejection as the expression of Bcl-2 in cholangiocytes is decreased as a
      consequence of bile duct lesions

PMID- 18320612
TI  - Current awareness in NMR in biomedicine.

PMID- 18320613
TI  - Re: Diagnosing skin cancer in primary care: how do main-stream general
      practitioners compare with primary care skin cancer clinic doctors?

PMID- 18320614
TI  - Orthopaedic surgeons, scientists, and industry.

PMID- 18320615
TI  - [Methods for mathematical data processing in enzyme immunoassay. I. Theoretical
      bases].
AB  - The paper deals with the mathematical processing of enzyme immunoassay (EIA)
      data. The paper comprises two parts. Part 1 contains a brief comparative account
      of the basic ways of presenting experimental data and constructing a standard
      curve, as well as practical guidelines for choosing the mathematical methods for
      calculation of concentrations. The recommendations proposed in Part II are based
      on the comparative study of photometric equipment and software that is of common
      use in EIA diagnosis at the Russian clinical laboratories. The experiment
      imitates competitive analysis illustrates a relationship of the obtained clinical
      result to the choice of either mode of constructing the standard graph on the
      basis of the optic densities of calibration samples. The findings indicate that
      an incorrectly chosen method for data processing may make both a false rejection
      of the whole analysis on the basis of the erroneous calculation of the
      concentration of a test agent in the control serum and to underdiagnosis on the
      basis of the erroneous calculation of the concentration of a test agent in a
      patient's sample near the point of taking a medical decision.

PMID- 18320616
TI  - [Methods for mathematical data treatment in enzyme immunoassay. II. comparative
      assessment of mathematical enzyme immunoassay data treatment methods used in
      various software].

PMID- 18320617
TI  - [Diagnosis of familial forms of hyperlipoproteinemia and their differential,
      etiologically justified dietotherapy (lecture 1)].

PMID- 18320618
TI  - [Cytological classification of nontoxic nodular goiter].
AB  - By comparing the cytological and histological data on thyroid nodular lesions in
      715 patients, the authors have arrived at the conclusion that with a cytological
      response of colloidal goiter and colloidal goiter with adenomatosis, the cancer
      detection rate is not greater than 4%. With a cytological response of
      adenomatosis with atypia and follicular tumor, a malignancy occurs in 9 to 13%.
      It is recommended that cytological data should be grouped by the type of a
      morphological classification of thyroid nodular diseases: colloidal goiter (with
      regression, proliferation, adenomatosis, cystic cavity); tumors (adenomatosis
      with atypia, follicular tumor); cancer.

PMID- 18320619
TI  - Social justice is a global issue: ethical pandemic planning.

PMID- 18320620
TI  - Case study. "Doctor, will you turn off my LVAD?" Commentary.

PMID- 18320621
TI  - Attention diverted from real issue.

PMID- 18320622
TI  - Pull up a chair and share.

PMID- 18320623
TI  - Design of phase-modulated broadband refocusing pulses.
AB  - Broadband linear-phase refocusing pulses were designed with the Shinnar-Le Roux
      (SLR) transformation and verified experimentally. The design works in several
      steps: initially, a linear-phase B polynomial is created with the Parks
      McClellan/Remez exchange algorithm. The complementary A polynomial required for
      the SLR transformation is generated with the Hilbert transformation, yielding the
      minimum-phase response. The phase response of the A polynomial is altered by zero
      flipping, which changes the overall pulse shape while retaining its refocusing
      profile. Optimal pulses in terms of minimal B(1max) and hence broadest bandwidth
      were found with non-linear optimisation of the zero-flipping pattern. These
      pulses are generally phase modulated with a time-symmetric amplitude and anti
      symmetric phase modulation. In this work, a whole range of pulses were designed
      to demonstrate the underlying relationships. Five exemplary pulses were
      implemented into a PRESS sequence and validated by acquiring images of a water
      oil phantom and lactate spectra at TE = 144 ms.

PMID- 18320624
TI  - Part 2: Readers' and author's responses to "We all need healthcare; who needs
      'insurance"?

PMID- 18320625
TI  - Readers' and author's responses to "Evidence-based standards should apply to
      dietary supplements, too".

PMID- 18320626
TI  - Readers' and author's responses to "Evidence-based standards should apply to
      dietary supplements, too".

PMID- 18320627
TI  - Readers' and author's responses to "Evidence-based standards should apply to
      dietary supplements, too".

PMID- 18320628
TI  - Readers' and author's responses to "The disappearing patient".

PMID- 18320629
TI  - Readers' and author's responses to "The disappearing patient".

PMID- 18320630
TI  - Readers' and author's responses to "We all need healthcare; who needs
      'insurance'?".

PMID- 18320631
TI  - Readers' and author's responses to "We all need healthcare; who needs
      'insurance'?".

PMID- 18320632
TI  - Readers' and author's responses to "We all need healthcare; who needs
      'insurance'?".

PMID- 18320633
TI  - Readers' and author's responses to "We all need healthcare; who needs
      'insurance'?".

PMID- 18320634
TI  - Readers' and author's responses to "We all need healthcare; who needs
      'insurance'?".

PMID- 18320635
TI  - Comparative analysis of anxiety-like behaviors and sensorimotor functions in two
      rat mutants, ci2 and ci3, with lateralized rotational behavior.
AB  - There is increasing evidence that developmental anomalies of cerebral asymmetry
      are involved in the etiology of psychiatric disorders, including schizophrenia,
      depression and anxiety. Thus, rodents with abnormal cerebral lateralization are
      interesting tools to study the association between such anomalies and behavioral
      dysfunction. The most studied indicator of cerebral asymmetry in the rat is that
      of circling or rotational behavior. We have recently described two rat mutants,
      ci2 and ci3, in which lateralized rotational behavior occurs either spontaneously
      or in response to external stimuli, such as new environment or handling. While
      cochlear and vestibular defects are found in 52 rats, ci3 rats do not exhibit any
      inner ear abnormalities. The abnormal motor response to external stimuli raised
      the possibility that the circling rat mutants may be more likely to express
      anxiety-related behavior in tests of emotionality. In the present study, we
      characterized anxiety-related behaviors of ci2 and ci3 rats in the open field,
      elevated plus-maze and light/dark exploration test. Furthermore, sensorimotor
      functions of these rats were evaluated by the rotarod, accelerod and wire hang
      tests. Heterozygous (ci2/+) littermates or rats of the respective background
      strains (LEW, BH.7A) were used as controls. In contrast to our expectation, both
      mutants demonstrated less anxiety-related behavior than controls in tests of
      emotionality. Ci3 rats exhibited normal sensorimotor functions, whereas marked
      impairment was observed in ci2 rats, which is most likely a consequence of the
      vestibular dysfunction in these animals. The acoustic startle response (ASR) and
      prepulse inhibition of ASR did not differ between ci3 rats and controls. The
      reduced emotionality of the mutant rats indicated by the present experiments may
      not be specifically linked to anxiety per se, but is maybe more reflective of
      impulsivity or the inability to normally perceive or process potentially
      threatening situations. Based on previous findings of dysfunctions of the central
      dopamine system in ci2 and ci3 mutant rats, we assume that alterations in
      dopaminergic activity are involved in the maladaptive behavior observed in the
      present study.

PMID- 18320636
TI  - Russia's next president needs to tackle health reforms.

PMID- 18320637
TI  - Exotic abortifacients and lost knowledge.

PMID- 18320638
TI  - Efficacy of antidotal treatment against sarin poisoning: the superiority of
      benactyzine and caramiphen.
AB  - Sarin, a potent cholinesterase inhibitor, induces an array of toxic effects
      including convulsions and behavioral impairments. We report here on the
      protection provided by post-exposure antidotal treatments against a lethal dose
      of sarin (1.2xLD50) by scopolamine, benactyzine, trihexyphenidyl or caramiphen,
      administered 5, 10 or 20 min after the initiation of convulsions. A mixture of
      the oxime TMB4 and atropine (TA) was injected 1 min following poisoning a
      paradigm that may represent a scenario reminiscent of a terror incident.
      Surviving TA-treated rats exhibited marked tonic-clonic convulsions, weight loss,
      poor clinical status and abnormal cognitive performance as assessed by the Morris
      water maze. Additionally, a dramatic increase in the density of peripheral
      benzodiazepine receptors (PBRs), a faithful marker for neuronal damage, was
      noted. Animals treated 5 min after the development of toxic signs with
      benactyzine, trihexyphenidyl or caramiphen demonstrated control levels of PBR
      values, whereas scopolamine produced binding densities significantly above basal
      levels. Examined at the 10-min time point, scopolamine and trihexyphenidyl
      afforded no protection against brain damage and did not differ from TA-injected
      rats. All four drugs failed to significantly prevent the alterations when applied
      20 min after onset of convulsions. Assessment of learning processes yielded
      similar results, where caramiphen exibited some protection at the 20-min time
      point. Our results show that caramiphen and benactyzine, agents with combined
      anticholinergic and antiglutamatergic pharmacological profiles, offer
      considerable shielding against sarin, even when their administration is delayed.

PMID- 18320639
TI  - Local and translational dynamics in DNA-lipid assemblies monitored by solid-state
      and diffusion NMR.
AB  - The influence of electrostatic interactions on the dynamic properties of
      complexes containing DNA and mixtures of cationic- (DDA) and zwitterionic (DLPC)
      lipids are studied by means of NMR. The systems are arranged in lamellar membrane
      stacks intercalated by DNA molecules. This is confirmed by 31P-NMR, where a
      superposition of an axially symmetric powder pattern arising from the
      phospholipid membrane and an asymmetric tensor due to DNA can be fitted to the
      experimentally observed lineshape. The local mobility and order is assessed using
      two solid-state NMR techniques applicable to samples with natural isotopic
      abundance: WIdeline SEparation (WISE) and Separated Local Field (SLF)
      spectroscopy. Both experiments yield highly resolved 13C spectra in the direct
      dimension. The indirect dimension contains information about molecular dynamics
      through the 1H dipolar linewidth (WISE) or the 1H(-13)C dipolar coupling constant
      (SLF). The experiments suggest that DNA is static while it induces an increased
      disorder in the hydrocarbon chains as compared to the parent lipid case. DDA
      chain order is more affected than DLPC due to the attractive electrostatic
      interaction between DNA and the cationic lipid. Translational dynamics of the
      lipids and the water was measured with the Pulsed Field Gradient STimulated Echo
      (PFG STE) technique. The influence of lamellar domain size and the angular
      dependence of the diffusion coefficients and nuclear relaxation times on the
      results of the PFG STE experiments are discussed. The local water diffusion
      coefficient is reduced by a factor four from the value of bulk water, and
      increases as the DLPC content is increased. We observe two lipid components with
      an order of magnitude difference in diffusion coefficients in the DNA:DDA:DLPC
      precipitate and these are assigned to DLPC (fast) and DDA (slow). Cationic lipid
      (DDA) diffusion is decreasing a factor of 2 when DLPC is added to the pure
      DNA:DDA system, indicating DNA-induced lipid segregation within the bilayer and
      the transition from locally 2D to 1D diffusion of the DDA. The results show that
      DNA-lipid electrostatic interactions reduce the long-range lipid mobility but
      locally enhance the hydrocarbon chain dynamics by perturbing the preferred lipid
      packing.

PMID- 18320640
TI  - Intramedullary thrombosed venous ectasia mimicking hemangioblastoma.

PMID- 18320641
TI  - [The state of natural resistance of organism in patients of different age with
      adhesive illness of peritoneum].
AB  - The state of natural resistance of organism according to the indices of thiol
      disulphid system in patients of various age, suffering the adhesive illness of
      peritoneum, and the donors was studied up. It was established, that the natural
      resistance of organism in some donors differs in accordance with their age and
      over the level of physiological norm. An acute adhesion ileus, as well as the
      pain form of adhesive illness coexists with inhibition of natural resistance of
      organism. In the pain form of adhesive illness in the patients aged 25 - 34 years
      the raising of thiol-disulphid substances ratio was observed. The changes of the
      natural resistance of organism state in accordance with the patients age may
      predispose to adhesive illness occurrence and further progressing.

PMID- 18320642
TI  - [Application of the composit allotransplants in the treatment of postoperative
      abdominal wall hernia].
AB  - There were analyzed the results of treatment of 75 patients, in whom
      postoperative abdominal wall hernia (POAWH) have occurred. The anterior abdominal
      wall alloplasty using polipropilene endoprostheses was performed in 50 patients
      and the large pore lightened composit nets--in 25. Peculiarities of postoperative
      period course and follow-up results were studied. First experience of application
      of the composit endoprostheses is positive according to reduction of the
      complications rate. Further studying of the application peculiarities of the
      lightened composit nets in patients suffering POAWH is imperative because of the
      patients quantity and follow-up shortage.

PMID- 18320643
TI  - [Application of mini-invasive technologies in the treatment of gastrointestinal
      bezoars].
AB  - The data on etiology, clinical signs, diagnosis and variety of approaches to the
      treatment of gastrointestinal bezoars were presented, basing on the worldwide
      literature analysis. The results of surgical treatment of patients for bezoars,
      using miniinvasive methods, are presented.

PMID- 18320644
TI  - [Significance of immunological investigations in the studying of various forms of
      cardiomyopathy].
AB  - The data concerning the role of the immune and inflammatory reactions activation
      in formation of dilatational and hypertrophic cardiomyopathy were presented. The
      dependence of the humoral-inflammatory disbalance progressing on the processes of
      the apoptosis and inflammatory cytokins level regulation, determining the immune
      answer disorder degree in relation with cardiomyopathy form, was established.

PMID- 18320645
TI  - [Peculiarities of surgical treatment of the Krohn's disease].

PMID- 18320646
TI  - [Double trichobezoar in a child].

PMID- 18320647
TI  - [The mitral valve abscess, which simulated the left ventricle tumor].

PMID- 18320648
TI  - [Laparoscopic reoperations after gastric banding for alimentary--constitutional
      obesity].
AB  - There were the literature data studied up and the results of own observations
      summarized about the patients after laparoscopic gastric banding and laparoscopic
      reoperations after gastric banding interventions in 72 persons, suffering
      obesity. Two procedures were used for gastric banding operation: in 1992-1999 yrs
      a "small" stomach was formed 50-100 ml in volume, the diameter of stenosed
      segment had constituted 10-11 mm, the ring was placed through the omental bursa;
      from 1999 yr--suprabursal placement of the bandage and formation of a "small"
      stomach 20-25 ml in volu me. In the immediate and late follow-up period the body
      mass was reducing adequately in up to 80% of the patients. The complications in
      the early postoperative period, demanding reoperation, had occurred in 4 (5.5%)
      of patients and in the late period--in 6 (8.3%). All of them laparoscopic
      reoperation was conducted. We consider, that in occurrence of early and late
      postoperative complications their correction is mandatory using laparoscopic
      technologies.

PMID- 18320649
TI  - [Pathogenetic aspects of surgical treatment of destructive pancreatitis].
AB  - Analysis of treatment efficacy in 270 patients suffering an acute pancreatitis
      was conducted. The main factor, which determines the choice of treatment, is
      etiology, pathogenesis and the form of an acute pancreatitis substantiation. The
      acute pancreatitis course phases, the main principles of diagnosis and treatment,
      depending on its phase, are discussed. This had permitted to lower lethality to
      7.2%.

PMID- 18320650
TI  - [Efficacy of antibiotic prophylaxis in surgical intervention on the liver,
      gallbladder, and biliary ducts].
AB  - Optimal schemes of antibioticoprophylaxis in conduction of operations on the
      liver, gallbladder, and biliary ducts, using the most effective antibiotics, were
      studied up. The analysis of the results trusts the necessity of conduction of
      antibioticoprophylaxis in majority of the patients, permitting to lower the
      purulent-septic complications rate in 3-8 times. An optimal schemes of
      atibioticoprophylaxis are the application of Zinacef or combination of Zinacef
      with metronidazol with the first injection made while the introduction narcosis
      conduction and continuing during first 2-3 days after the operation.

PMID- 18320651
TI  - [Pathology of urinary duct in surgical practice of regional hospital].

PMID- 18320652
TI  - Re: Recurrence after totally extraperitoneal laparoscopic repair: implications
      for operative technique and surgical training. Surgeon 2006; 4(5): 299-307.

PMID- 18320653
TI  - [Improvement of myocardial remodelling and functioning in patients undergoing
      surgical treatment of chronic cardiac insufficiency by two-staged elevation of
      the immunoregulatory reserve of autological bone marrow cells and their
      intramyocardial application].
AB  - The aim of the investigation was to study a possibility to improve left
      ventricular (LV) volume and function remodelling in patients with chronic cardiac
      insufficiency (CCI) by means oftwo-stage bone marrow cell (BMC) activation: first
      in vivo and then ex vivo within the process of their cultivation. Two groups of
      CCI patients were recruited. Group 1 (controls) consisted of 50 patients
      undergoing conventional aorto-coronary bypass surgery (ACBS). Group 2 consisted
      of 57 patients injected with 200 million autological mononuclear BMC
      intramyocardially during ACBS. In Group 2 patients, the severity of immune
      dysregulation was assessed initially using blood leukocyte stimulation index (SI)
      values. Sixteen patients with SI >1 and moderate immunographic alterations were
      considered to have a favorable prognosis for BMC treatment; 41 subjects with SI
      <1 and pronounced immunographic abnormalities were regarded as having an
      unfavorable prognosis for BMC application. Twenty-two patients with SI <1 were
      administered a preliminary immunocorrective course (in vivo BMC activation).
      Mononuclear BMC obtained from 38 patients with SI >1 and 19 patients with SI <1
      were cultured for 5 to 7 days (ex vivo BMC activation). Positive changes in BMC
      phenotypical pattern were observed only in patients with SI >1: CD3, CD4, CD8,
      CD25, and some other measurements increased. Significant positive effects on LV
      function parameters and Duke Activity Status Index (DASI) values were revealed in
      patients with SI >1 six months after BMC administration. In vivo immunocorrection
      in combination with subsequent ex vivo BMC activation (n=38) promoted significant
      improvements in LV volume characteristics 6 months after ACBS vs. the controls
      (ACBS without BMC, n=50). In conclusion, to make the administration of
      autological BMC in CCI patients effective, two-staged BMC activation should be
      performed: in vivo activation with immunocorrectors should be followed by ex vivo
      activation of cultured cells.

PMID- 18320654
TI  - [Peculiarities of medico-demographic processes in Russian Federation in the first
      half of the 21st century].
AB  - The authors analyze the modem dynamics in Russian population reproduction and its
      problems. Special attention is paid to the structure of mortality and regional
      variations in it. The mechanisms of changes beginning to take place nowadays, and
      their future development are discussed.

PMID- 18320655
TI  - [Causes of local forms of primary tuberculosis in ways of their detection in
      children in an area with high morbidity rates in the adult population].
AB  - Thirty-six children with new-onset local tuberculosis were followed up to assess
      its causes and the ways of its detection. The predominant form of primary
      tuberculosis was that of inthrathoracic lymph nodes. Six examinees had
      complicated tuberculosis, the latter being attended by circumscribed lymphogenic
      semination in 5 of them and by the bronchopulmonary syndrome in one. Eight
      patients were diagnosed as having a primary tuberculous complex. Tuberculin
      diagnosis revealed a primary tuberculous process in 33 of the 36 patients. In 25
      of the 36 patients, the diagnosis was established by the routine X-ray
      tomography. Computed tomography was performed in 11 patients, 3 of them being
      diagnosed as having minor tuberculosis of intrathoracic lymph nodes, it could
      specify the extent and site of the lesion in the remaining patients. The risk
      factors included ineffective or absent BCG vaccination; a family contact with a
      tuberculosis patient; no preventive measures in the nidus of infection;
      comorbidity; a family's social ill-being.

PMID- 18320656
TI  - [Clinical and morphological characteristics of peripheral lymph node
      tuberculosis].
AB  - This paper provides the clinical and morphological characteristics of
      tuberculosis of peripheral lymph nodes. The disease has been found to occur as a
      manifestation of the secondary period of tuberculous infection at the age of 21
      50 years and to be isolated and asymptomatic with reduced tuberculin sensitivity
      and immunity in the patients. The caseous and productive forms were detected in
      76.04 and 22.92%, respectively; the indurative form was found in the remaining
      1.04%. Mycobacterium tuberculosis was cultured in 26% cases of inoculation of
      puncture specimens and removed lymph nodes. The findings suggest the induced
      pathomorphism of peripheral node tuberculosis at the present stage that requires
      the development of new approaches to and methods for treating the patients.

PMID- 18320657
TI  - [Trends in the tuberculosis epidemiological situation in the Kemerovo Region
      according to the data of comprehensive evaluation].
AB  - The author analyzes trends in the tuberculosis epidemiological situation in the
      Kemerovo Region in 1985 to 2006 according to the data of comprehensive
      evaluation. The situation was best in 1991 and worst in 2005 with some tendency
      for stabilization in 2006. The trend of the epidemic situation in the region
      mainly corresponds to the country's average trend, but shows the worse pattern,
      which may account for the more marked socioeconomic crisis in the coal-mining
      area in the 1990s. Comprehensive evaluation shows that there is a direct and
      strong correlation of the tuberculosis epidemic situation among the children with
      that in the general population.

PMID- 18320658
TI  - [A new list of the leading reviewed scientific journals and editions to publish
      the primary research results of dissertations for academic degrees of candidate
      and doctor of sciences].

PMID- 18320659
TI  - [Itraconazole treatment in the suspension of pathological fungal colonization of
      the airway in patients with pulmonary tuberculosis].

PMID- 18320660
TI  - [Organization of antituberculous care at the medical level].

PMID- 18320661
TI  - [Analysis of platelet production following liver transplantation using the
      immature platelet fraction (IPF) parameter].
AB  - Although liver transplantation (LT) is frequently associated with
      thrombocytopenia, thrombopoiesis following LT remains to be evaluated. We
      analyzed platelet counts (PLT), immature Platelet Fraction (IPF), and
      thrombopoietin (TPO) in 8 patients with LT. PLT and IPF were measured using
      Sysmex XE-2100. TPO was measured with Human TPO ELISA Kit. In 7 of 8 patients
      with LT, IPF increased prior to the elevation of platelet counts. In 5 of 7
      patients with increased IPF, TPO levels increased simultaneously with IPF,
      suggesting that IPF may reflect the production of platelets in patients with LT.
      IPF and TPO might be useful to monitor the platelet production in patients
      following LT.

PMID- 18320662
TI  - [Clinical problems and prospects in laboratory chemical analysis].
AB  - The first subject of clinical problems is about uncertainty in measurement, but
      is now going be clarified by the standardization of reference measurement
      procedure and reference material. On the other hand, physiological uncertainty in
      samples is unable to be solved. So the establishment of evidence based diagnostic
      values is important in company with reference value, especially in the field of
      health examination. The life expectancy of the Japanese population is one of
      longest in the world. So the preventive medicine of lifestyle-related disease is
      important to perform an extensive research like as disease preventive biomarkers.
      Furthermore, we expect the progression of examinations in the pathophysiological
      diagnosis. I present the paper of development for the diagnostic method of
      dihydropyrimidine dehydrogenase-deficient as an example.

PMID- 18320663
TI  - New taste for kosher foods. Safety is a selling point.

PMID- 18320664
TI  - Plea to end fee-for-service plans. Providers say flaws in Medicare plan too
      costly.

PMID- 18320665
TI  - VA feels heat over Marion deaths. Officials apologize to families, say fixes to
      come.

PMID- 18320666
TI  - Change, but not in dollar bills. FDA needs more than money to fix problems:
      Congress.

PMID- 18320667
TI  - Calif. wants another slice of UnitedHealth pie. PacifiCare violations could cost
      insurer up to $1.3 billion.

PMID- 18320668
TI  - Another bite at the Orange. Third round of bidding for Anaheim Memorial.

PMID- 18320669
TI  - CMS lab demo meets resistance. Scripps, Sharp and Internist against three-year
      project.

PMID- 18320670
TI  - Letters of support. Proposal would expand number of agencies that can back tax
      exempt bonds.

PMID- 18320671
TI  - Prices spike in 2007. Hikes accelerate at hospitals; doc prices resume climb.

PMID- 18320672
TI  - More gain-sharing guidance. Inspector general's opinions point to more safe
      zones.

PMID- 18320673
TI  - The joint appeal. Froedtert, Columbia St. Mary's in Milwaukee choose joint
      operating agreement.

PMID- 18320674
TI  - Sharing the load. Let individuals, government, employers split costs: poll.

PMID- 18320675
TI  - Private patients' unpaid bills leave trusts chasing millons.

PMID- 18320676
TI  - Inequality. A tale of two cities and beyond: why getting even is proving tricky.

PMID- 18320677
TI  - On big picture partnerships.

PMID- 18320678
TI  - Older people. In search of the person behind the condition.

PMID- 18320679
TI  - Data briefing. An unequall race?

PMID- 18320680
TI  - CTOs. Tall order?

PMID- 18320681
TI  - Patients denied admission as PCTs argue over who will pay.

PMID- 18320682
TI  - Care outside hospital. Community hospitals grab local care lifeline.

PMID- 18320683
TI  - On the dilemmas of allocation.

PMID- 18320684
TI  - Prevention is better than cure, but by how much?

PMID- 18320685
TI  - Data briefing. System change hits activity records.

PMID- 18320686
TI  - The mother of all studies.

PMID- 18320687
TI  - Mental health. Strength in numbers.

PMID- 18320688
TI  - Coronary heart disease. At the heart of change.

PMID- 18320689
TI  - Coaching. Yes, you can phone a friend.

PMID- 18320690
TI  - Anti-HIV agents. Using only lopinavir/ritonavir (Kaletra).

PMID- 18320691
TI  - Anti-HIV agents.  A trial of Kaletra monotherapy.

PMID- 18320692
TI  - Anti-HIV agents.  Monotherapy studies--points to  consider.

PMID- 18320693
TI  - Anti-HIV agents. What makes a viral load blip?

PMID- 18320694
TI  - Case study. "Doctor, will you turn off my LVAD?" Commentary.

PMID- 18320695
TI  - [A 50 year-old man with abdominal tumor].

PMID- 18320696
TI  - Understanding the complexity of the U.S. health care system: can free-market
      ideology respond to a current challenge?

PMID- 18320697
TI  - [Bilateral sixth and unilateral partial third craneal nerve palsies after lumbar
      puncture].

PMID- 18320698
TI  - [Day hospital as conventional hospitalization alternative in an internal medicine
      service of a first level center].

PMID- 18320699
TI  - [Neurological symptoms as only one expression of fat embolism syndrome in
      politraumatized patient].

PMID- 18320700
TI  - [Madelung disease and Raynaud].

PMID- 18320701
TI  - The tragic Mary: a case study in Michael Field's understanding of sexual
      politics.

PMID- 18320702
TI  - The origins of British military psychiatry before the First World War.

PMID- 18320703
TI  - [Advertising before, during, and after World War I: the example of the
      Rottenburger Zeitung].

PMID- 18320704
TI  - [Foreigners in the homeland: the rise and fall of German minority groups in
      Austrian Trieste].

PMID- 18320705
TI  - "Out of the cage"? Women and the First World War in Pontypridd.

PMID- 18320706
TI  - Minute ventilation recovery time measured using a new, simplified methodology
      predicts extubation outcome.
AB  - Extubation failure is associated with poor intensive care unit and hospital
      outcomes. Minute ventilation recovery time, an integrative measure of a patient's
      respiratory reserve, has been shown in a pilot study to predict extubation
      outcome; however, the methodology is subjective and impractical for routine use.
      The authors hypothesize that minute ventilation recovery time, measured using an
      objective and simpler method, would predict extubation outcome. A prospective
      cohort study was performed in adult medical and surgical intensive care unit
      patients intubated for >24 hours who were weaning from mechanical ventilation.
      Minute ventilation recovery time was measured using a new, simplified, and
      objective method following the final spontaneous breathing trial prior to
      extubation. The primary outcome was extubation failure, defined as reintubation
      within 7 days. The study cohort comprised 88 patients, of whom 22 (25%) failed
      extubation after a median of 3 days. Demographic data, weaning parameters, and
      the proportion of patients who passed an extubation screen were similar between
      groups (P > .05). Minute ventilation recovery time was significantly longer in
      patients who failed extubation (15 [5-15] vs 2 [1-5] minutes, P < .001),
      consistent in both medical and surgical subgroups. Operating characteristics for
      a preliminary threshold (minute ventilation recovery time >or=5 minutes) for
      prediction of extubation failure were sensitivity = 0.78, specificity = 0.71,
      positive predictive value = 0.47, negative predictive value = 0.90, correctly
      classified = 0.72. Adjustment for significant covariates did not alter the
      relationship between minute ventilation recovery time >or=5 minutes and
      extubation failure (odds ratio = 4.9, 95% confidence interval 1.45-16.2, P <
      .02). C statistic was 0.79 +/- 0.17. It was concluded that minute ventilation
      recovery time, measured using a feasible methodology, can predict extubation
      outcome in medical and surgical intensive care unit patients.

PMID- 18320707
TI  - Efficacy of magnesium-amiodarone step-up scheme in critically ill patients with
      new-onset atrial fibrillation: a prospective observational study.
AB  - Amiodarone is considered a first-choice antiarrhythmic drug in critically ill
      patients with new-onset atrial fibrillation (AF). However, evidence supporting
      the use of this potentially toxic drug in critically ill patients is scarce.
      Magnesium sulphate (MgSO4) has shown to be effective for both rate and rhythm
      control, to act synergistically with antiarrhythmic drugs, and to prevent
      proarrhythmia. Treatment with MgSO4 may reduce the need for antiarrhythmic drugs
      such as amiodarone in critically ill patients with new-onset atrial fibrillation.
      The efficacy of a new institutional protocol was evaluated. Patients were treated
      with a new institutional protocol for new-onset atrial fibrillation in critically
      ill patients. An MgSO4 bolus (0.037 g/kg body weight in 15 minutes) was followed
      by continuous infusion (0.025 g/kg body weight/h). Intravenous amiodarone
      (loading dose 300 mg, followed by continuous infusion of 1200 mg/24 h) was given
      to those not responding to MgSO4 within 1 hour. Clinical response was defined as
      conversion to sinus rhythm or decrease in heart rate <110 beats/min. Sixteen of
      the 29 patients responded to MgSO4 monotherapy, whereas the addition of
      amiodarone was needed in 13 patients. Median (range) time until conversion to
      sinus rhythm after MgSO4 was 2 (1-45) hours. Median (range) conversion time in
      patients requiring amiodarone was 4 (2-78) hours, and median (range) conversion
      time in all patients was 3 (1-78) hours. The 24-hour conversion rate was 90%.
      Relapse atrial fibrillation was seen in 7 patients. The magnesium-amiodarone step
      up scheme reduces the need for amiodarone, effectively converts new-onset atrial
      fibrillation into a sinus rhythm within 24 hours, and seems to be safe in
      critically ill patients.

PMID- 18320708
TI  - Adipocyte differentiation of 3T3-L1 preadipocytes is dependent on lipoxygenase
      activity during the initial stages of the differentiation process.
AB  - Adipocytes play a central role in whole-body energy homoeostasis. Complex
      regulatory transcriptional networks control adipogensis, with ligand-dependent
      activation of PPARgamma (peroxisome proliferator-activated receptor gamma) being
      a decisive factor. Yet the identity of endogenous ligands promoting adipocyte
      differentiation has not been established. Here we present a critical evaluation
      of the role of LOXs (lipoxygenases) during adipocyte differentiation of 3T3-L1
      cells. We show that adipocyte differentiation of 3T3-L1 preadipocytes is
      inhibited by the general LOX inhibitor NDGA (nordihydroguaiaretic acid) and the
      12/15-LOX selective inhibitor baicalein. Baicalein-mediated inhibition of
      adipocyte differentiation was rescued by administration of rosiglitazone.
      Treatment with baicalein during the first 4 days of the differentiation process
      prevented adipocyte differentiation; supplementation with rosiglitazone during
      the same period was sufficient to rescue adipogenesis. Accordingly, we
      demonstrate that adipogenic conversion of 3T3-L1 cells requires PPARgamma ligands
      only during the first 4 days of the differentiation process. We show that the
      baicalein-sensitive synthesis of endogenous PPARgamma ligand(s) increases rapidly
      upon induction of differentiation and reaches a maximum on days 3-4 of the
      adipocyte differentiation programme. The conventional platelet- and leucocyte
      type 12(S)-LOXs and the novel eLOX-3 (epidermis-type LOX-3) are expressed in
      white and brown adipose tissue, whereas only eLOX-3 is clearly expressed in 3T3
      L1 cells. We suggest that endogenous PPARgamma ligand(s) promoting adipocyte
      differentiation are generated via a baicalein-sensitive pathway involving the
      novel eLOX-3.

PMID- 18320709
TI  - Are nurses still paying for the UKCC's mistakes?

PMID- 18320710
TI  - Cholesterol ester transfer protein inhibition with torcetrapib leads to an
      increase in cardiovascular events: an effect that is unlikely to be the result of
      increases in blood pressure alone.

PMID- 18320711
TI  - Sports nutrition and Australian football.

PMID- 18320712
TI  - A leader who listens.

PMID- 18320713
TI  - Q & A with Dr. Cadle.

PMID- 18320714
TI  - Human cord blood cells can differentiate into retinal nerve cells.
AB  - Retinal degeneration and dystrophy are the major causes of blindness in the
      developed world. It has been reported that human cord blood cells (HCBCs) can
      differentiate into neuron-like cells in vitro. We have recently demonstrated that
      bone marrow cells (BMCs) of both mice and rats can differentiate into retinal
      nerve cells (RNCs). In the present study, we show the differentiation capacity of
      HCBCs into RNCs in vivo. We transplanted lineage-negative HCBCs into the
      subretinal space of severe combined immunodeficiency (SCID) mice. Two weeks after
      the transplantation, some of the transplanted cells expressed human nestin, human
      MAP2, human neuron specific enolase (NSE), beta-III tubulin and also rhodopsin.
      These results indicate that HCBCs can differentiate into RNCs and suggest that
      our new strategy could be used for the regeneration of retinal nerve cells in
      degenerative or dystrophic diseases.

PMID- 18320715
TI  - A simplified method for generating oligodendrocyte progenitor cells from neural
      precursor cells isolated from the E16 rat spinal cord.
AB  - Conditioned medium obtained from B104 neuroblastoma cells (B104CM) has been used
      widely for inducing oligodendrocyte progenitor cells (OPCs) from neural precursor
      cells (NPCs). Our previous studies have demonstrated that E16 rat spinal cord
      derived NPCs could be induced to differentiate into OPCs using a combination of
      B104CM and basic fibroblast growth factor (bFGF). Here we report the development
      of a more efficient and reliable approach to generate large quantities of highly
      purified OPCs from spinal cord-derived NPCs using a combination of platelet
      derived growth factor (PDGF) and bFGF. We demonstrated that, after the two
      factors application, over 90% cells displayed typical bipolar or tripolar
      morphology and expressed markers for OPCs including A2B5 (90.36 +/- 4.59%), NG2
      (93.63 +/- 3.37%) and platelet derived growth factor alpha receptor (PDGFR; 90.35
      +/- 1.95%). Our results indicated that the PDGF/bFGF combination is more
      efficient in generating OPCs than the B104CM/bFGF. And it is a more potent
      combination of factors in promoting proliferation of OPCs.

PMID- 18320716
TI  - Dopamine, serotonin and noradrenaline changes in the striatum of C57BL mice
      following myelin oligodendrocyte glycoprotein (MOG) 35-55 and complete Freund
      adjuvant (CFA) administration.
AB  - Many data suggest involvement of inflammation in neurodegeneration. However, the
      exact mechanisms of this cooperation are poorly understood. We have previously
      shown that induction of inflammatory reaction, both before and after injury of
      the striatum, affects regeneration of dopaminergic neurons. In the present
      research we studied the role of inflammatory reaction in non-injured striatum. We
      used myelin oligodendrocyte glycoprotein (MOG) 35-55 in complete Freund's
      adjuvant (CFA) to elicit experimental autoimmune encephalomyelitis (EAE) mice
      model. As determined by HPLC, striatal dopamine (DA) and serotonin levels in mice
      treated with either MOG 35-55 in CFA or CFA alone were significantly higher
      compared to vehicle-treated controls on 13th day after induction. The ratio of
      homovanilic acid/dopamine (HVA/DA) and 3, 4 dihydroxyphenylacetic acid/dopamine
      (DOPAC/DA) were significantly lower in the MOG and CFA groups on 13th day,
      indicating decreased DA metabolism. Noradrenaline (NA) concentration did not
      differ between groups. Moreover, the striatal mRNA IL-1beta and TNF-alpha levels
      were elevated during induction phase of EAE in both groups, as determined by RT
      PCR. Our data indicate regulatory connection between dopaminergic and immune
      systems.

PMID- 18320717
TI  - Increase in the effectiveness of somatodendritic 5-HT-1A receptors in a rat model
      of tardive dyskinesia.
AB  - The present study concerns responsiveness of pre- and postsynaptic 5
      hydroxytryptamine (5-HT)-1A receptors in a rat model of tardive dyskinesia (TD).
      Vacuous chewing movements (VCMs) in rats are widely accepted as an animal model
      of TD. Results show that haloperidol injected at a dose of 1 mg/kg twice a day
      for 5 weeks elicited VCMs, which increased in a time dependent manner following
      the drug administration for 3-5 weeks. Tolerance was produced in motor
      coordination during the potentiation of VCMs. Exploratory activity in an open
      field and in an activity box decreased in haloperidol treated animals. The
      effects of 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT; 0.5 mg/kg) were
      monitored 48-h after withdrawal from repeated administration of haloperidol. 8-OH
      DPAT-induced locomotion was greater in haloperidol treated rats. 5-HT synthesis
      increased in haloperidol treated animals, while 8-OH-DPAT-induced decreases of 5
      HT synthesis were greater in repeated haloperidol than repeated saline injected
      animals. The results suggest that an increase in the effectiveness of
      somatodendritic 5-HT-1A receptors may decrease the inhibitory influence of 5-HT
      on the activity of dopaminergic neurons to precipitate VCMs. The 5-HT-1A agonist
      may help to alleviate neuroleptic-induced TD.

PMID- 18320718
TI  - Injections of vehicle, but not cyclosporin A or tacrolimus (FK506), afford
      neuroprotection following injury in the developing rat brain.
AB  - Susceptibility of the injured rat brain to seizures depends on the developmental
      stage at which the injury had been inflicted. Our previous study shows that
      tacrolimus (FK506) and cyclosporin A (CsA) applied following the injury can also
      decrease or increase the seizure susceptibility in an age-dependent way. To find
      possible neuronal substrates of the effects, we examined influences of the agents
      on the injured brain and on its neuronal population. Rat brains were mechanically
      injured on postnatal days 6 (P6) or 30 (P30). Twenty minutes and 24 hours
      following the injury, FK506 or CsA were injected in clinically used
      pharmaceutical formulations (Prograf or Sandimmun, respectively). The brains were
      fixed on postnatal day 60 and processed for histological examinations. To detect
      if negative effects of the injury could be abolished by the treatments, we
      examined the brain weight, the size of the injured region, and the nerve cell
      density, including the density of calretinin- and parvalbumin-immunopositive
      cells. We have found that long-term effects of treatments with the FK506- and CsA
      containing pharmaceutical formulations were never better than those of the
      vehicle alone (Cremophor and ethanol mixture). Moreover, the treatments could
      even amplify negative consequences of the injury alone. It could, therefore, be
      concluded that all the neuroprotective effects observed in the present study
      resulted exclusively from the influence of the vehicle alone. These effects of
      the brain injury and of subsequent treatments performed at different
      developmental stages were considered as possible determinants of further increase
      or decrease in susceptibility to seizures observed in adulthood.

PMID- 18320719
TI  - Central estrogen-like effect of genistein on growth hormone secretion in the ewe.
AB  - The present study tested a hypothesis, whether plant-derived genistein influences
      the secretion of growth hormone (GH) in ewes, acting directly within the central
      nervous system (CNS). Starting six weeks after ovariectomy, ewes were infused
      intracerebroventricularly with genistein (n = 5) or 17beta-estradiol (n = 5),
      both in a total dose of 40 microg/400 microl/4 h, or with a vehicle (control, n =
      5). All infusions were performed from 10:00 AM to 2:00 PM and blood samples were
      collected from 8:00 AM to 8:00 PM at 10-min intervals. Five genistein- and three
      vehicle-infused ewes were slaughtered the following morning. The plasma GH
      concentration was assayed by the radioimmunoassay method, and immunoreactivity of
      GH in the adenohypophysis was determined by immunohistochemistry. In genistein
      infused ewes, mean plasma GH concentration was significantly higher during the
      whole period of infusion than the concomitant concentration in vehicle-infused
      ewes. However, examining data within group, GH secretion rose gradually, reaching
      a significant value during the second phase of genistein infusion. In 17beta
      estradiol-infused animals, a significant increase in GH concentration was noted
      during the first two hours of the infusion, in comparison with vehicle-infused
      and also in comparison with genistein-infused ewes. Although a gradual increase
      in basic GH secretion continued in all treated groups during the afternoon and
      evening, mean plasma GH concentrations in genistein- and 17beta-estradiol-infused
      ewes were still significantly higher than in the vehicle-infused. The percentage
      of GH-positive cells in the adenohypophysis and the density of immunoreactive
      material in these cells decreased significantly in genistein-infused ewes,
      compared to the control, indicating diminished hormone storage. In conclusion,
      genistein as 17beta-estradiol, is an effective stimulator of GH secretion in ewes
      and may exert its effect at the level of the CNS.

PMID- 18320720
TI  - Distribution of the parvalbumin, calbindin-D28K and calretinin immunoreactivity
      in globus pallidus of the Brazilian short-tailed opossum (Monodelphis domestica).
AB  - This study describes the topography, borders and divisions of the globus pallidus
      in the Brazilian short-tailed opossum (Monodelphis domestica) and distribution of
      the three calcium binding proteins, parvalbumin (PV), calbindin D-28k (CB) and
      calretinin (CR) in that nucleus. The globus pallidus of the opossum consists of
      medial and lateral parts that are visible with Nissl or Timm's staining and also
      in PV and CR immunostained sections. Neurons of the globus pallidus expressing
      these proteins were classified into three types on the basis of size and shape of
      their soma and dendritic tree. Type 1 neurons had medium-sized fusiform soma with
      dendrites sprouting from the opposite poles. Neurons of the type 2 had medium-to
      large, multipolar soma with scarce, thin dendrites. Cell bodies of type 3 neurons
      were small and either ovoid or round. Immunostaining showed that the most
      numerous were neurons expressing PV that belonged to all three types. Density of
      the PV-immunopositive fibers and puncta correlated with the density of the PV
      labeled neurons. Labeling for CB resulted mainly in the light staining of
      neuropil in both parts of the nucleus, while the CB-expressing cells (mainly of
      the type 2) were scarce and placed only along the border of the globus pallidus
      and putamen. Staining for calretinin resulted in labeling almost exclusively the
      immunoreactive puncta and fibers that were distributed with medium-to-high
      density throughout the nucleus. Close to the border of globus pallidus with the
      putamen these fibers (probably dendrites) were long, thin and varicous, while
      more medially bundles of thick, short and smooth fibers predominated. Single CR
      ir neurons (all of the type 3) were scattered through the globus pallidus.
      Colocalization of two calcium binding proteins in one neuron was. never observed.
      The CB-ir puncta (probably terminals of axons projecting to the nucleus)
      frequently formed basket-like structures around the PV-ir neurons. Therefore, the
      globus pallidus in the opossum, much as that in the rat, consists of a
      heterogeneous population of neurons, probably playing diversified functions.

PMID- 18320721
TI  - Double stimulation modulates afterhyperpolarization phase following action
      potentials evoked in rat motoneurones.
AB  - The influence of a pair of stimuli running in time sequence between 5-10 ms (a
      doublet) on the basic parameters of antidromic action potentials was studied in
      rat motoneurones. Electrophysiological experiments were based on stimulation of
      axons in the sciatic nerve and intracellular recording of antidromic action
      potentials from individual motoneurones located in L4-L5 segments of the spinal
      cord. The following parameters were analyzed after application of a single
      stimulus and a doublet: amplitude and duration of the antidromic spike,
      amplitude, total duration, time to minimum, half-decay time of the
      afterhyperpolarization (AHP). It was demonstrated that application of a pair of
      stimuli resulted in: (1) a prolongation of action potentials, (2) a prolongation
      of the total duration and half-decay time of the AHP, (3) a decline of the time
      to minimum of the AHP, (4) an increase of the AHP amplitude of the spike evoked
      by the second stimulus. Significant differences in AHP parameters were found
      either in fast or slow motoneurones. We suppose that doublet-evoked changes in
      the AHP amplitude and duration are linked to intrinsic properties of individual
      motoneurones and may lead to the prolongation of the time interval to subsequent
      motoneuronal discharges during voluntary activity.

PMID- 18320722
TI  - Modulation of hippocampal theta rhythm by the opioid system of the
      pedunculopontine tegmental nucleus.
AB  - The pedunculopontine tegmental nucleus (PPN) belongs to the brainstem system
      which synchronizes hippocampal activity. Theta relevant intra-PPN circuitry
      involves its cholinergic, GABA-ergic and glutamatergic neurons and Substance P as
      neuromodulator. Evidence that PPN opioid elements also modulate the hippocampal
      theta is provided here. In urethane-anesthetized rats a unilateral microinjection
      of morphine (MF) (1.5 and 5 microg) increased the maximal peak power of tail
      pinch-induced theta. The higher dose also increased the corresponding frequency.
      When the theta was evoked by intra-PPN injection of carbachol (10 microg), the
      addition of MF (5 microg) prolonged theta latency and shortened the duration of
      the theta. These effects of MF were blocked by naloxone (5 microg). The results
      obtained suggest that the PPN opioid system can enhance or suppress the
      hippocampal theta depending on the actual level of PPN activation.

PMID- 18320723
TI  - Arousal and activation effects on physiological and behavioral responding during
      a continuous performance task.
AB  - Based on previous work indicating different neural substrates, two aspects of
      energetic state, "arousal" and "activation", have been conceptualized separately
      in our laboratory. "Arousal" has been defined as the energetic state at any
      particular time, and task-related "activation" as the task-related change in
      state from resting baseline to the task situation. Both are reflected in
      electrodermal activity and measured by skin conductance level. Our previous
      studies in this area have indicated that physiological responses to stimuli in a
      task are dependent on the arousal level at the time of stimulus presentation,
      rather than the task-related activation. In contrast, performance on the task is
      dependent on the task-related activation, rather than the current arousal level.
      That is, different aspects of the individual's state determine physiological and
      behavioral responses. Those studies had examined between-subjects differences in
      arousal and activation. The present study investigated the relevance of this
      separation in an across-subjects examination of fluctuations in arousal and
      activation, and their effects on physiological and behavioral responses, during a
      continuous performance task. It was found that the magnitude of the phasic
      orienting reflex to the targets during the task was dependent mainly on arousal,
      rather than task-related relative activation. Reaction time improved with
      increasing relative activation, but not with arousal. These findings support our
      earlier conclusions relating to the usefulness of arousal and activation as
      distinguishable features of the energetics of physiological and behavioral
      functions.

PMID- 18320724
TI  - Effects of neonatal maternal deprivation and postweaning environmental complexity
      on dendritic morphology of prefrontal pyramidal neurons in the rat.
AB  - It has been reported that periodic maternal separation in rats leads to a variety
      of endure behavioral, neurochemical and microstructural sequelae associated with
      the pathophysiology of anxiety disorders. Since it has been proposed that these
      changes might be permanent, we examined whether environmental complexity aid to
      recover the structural dendritic impairment induced by neonatal maternal
      deprivation in the medial prefrontal cortex of the rat. In addition, the anxiety
      like behavior was assessed in the elevated plus-maze. Repeated maternal
      separation between postnatal days 6-21 (3 hours daily) significantly reduced the
      dendritic material in layer II/III pyramidal neurons and induced anxiety-like
      behaviors in the elevated plus maze. Furthermore, environmental stimulation
      (twice a day, 1 h each) during 12 consecutive days (postnatal days 23-35) failed
      to recover the neuronal and behavioral disorders induced by neonatal maternal
      separation. The results demonstrated that (i) neonatal maternal separation
      severely altered pyramidal dendritic outgrowth in close association with anxiety
      like behavior assessed in the elevated plus maze, and (ii) postweaning
      environmental complexity was unable to recover neither the prefrontocortical
      neuronal impairment nor the novelty-induced anxiety-like behavior triggered by
      early maternal deprivation.

PMID- 18320725
TI  - Dopamine, learning, and reward-seeking behavior.
AB  - Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the
      brain. DA has been shown to be involved in the control of movements, the
      signaling of error in prediction of reward, motivation, and cognition. Cerebral
      DA depletion is the hallmark of Parkinson's disease (PD). Other pathological
      states have also been associated with DA dysfunction, such as schizophrenia,
      autism, and attention deficit hyperactivity disorder in children, as well as drug
      abuse. DA is closely associated with reward-seeking behaviors, such as approach,
      consumption, and addiction. Recent researches suggest that the firing of DA
      neurons is a motivational substance as a consequence of reward-anticipation. This
      hypothesis is based on the evidence that, when a reward is greater than expected,
      the firing of certain DA neurons increases, which consequently increases desire
      or motivation towards the reward.

PMID- 18320726
TI  - Export of electronics equipment waste.
AB  - Electronics equipment waste ("e-waste") includes discarded computers, computer
      monitors, television sets, and cell phones. Less than 10% of e-waste is currently
      recycled. The United States and other developed countries export e-waste
      primarily to Asia, knowing it carries a real harm to the poor communities where
      it will be discarded. A 2006 directive bans the use of lead, mercury, cadmium,
      hexavalent chromium, and certain brominated flame retardants in most electronics
      products sold in the EU. A similar directive facilitates the development and
      design of clean electronics products with longer lifespans that are safe and easy
      to repair, upgrade, and recycle, and will not expose workers and the environment
      to hazardous chemicals. These useful approaches apply only regionally and cover
      only a fraction of the hazardous substances used in electronics manufacture,
      however. There is an urgent need for manufacturers of electronics products to
      take responsibility for their products from production to end-of-life, and for
      much tighter controls both on the transboundary movement of e-waste and on the
      manner in which it is recycled. Manufacturers must develop clean products with
      longer lifespans that are safe and easy to repair, upgrade, and recycle and will
      not expose workers and the environment to hazardous chemicals.

PMID- 18320727
TI  - Employers' concerns regarding research participation.
AB  - Occupational health research depends on the cooperation and participation of
      employers. The authors describe employers' reasons for non-participation in a
      prospective study examining risk factors for carpal tunnel syndrome (CTS) and the
      usefulness of preplacement, post-offer nerve conduction screening. Companies were
      contacted to solicit participation. Non-participation explanations were reviewed.
      Of 73 eligible employers, 58 declined participation (participation rate: 20.5%).
      Reasons for non-participation included lack of interest (32.8%), liability
      concerns (awareness of CTS may increase workers' compensation claims) (22.4%),
      time constraints (19%), lack of direct benefit to the employer (8.6%), and
      company policy restraints (6.9%). Data from one employer were reviewed to
      determine whether workers' compensation claims for upper extremity disorders
      increased as a result of study participation. Claim rates showed no change in
      trend pre- and post-study inception. Expanding much-needed research to prevent
      occupational injuries and illnesses requires addressing employers' concerns and
      promoting research benefits.

PMID- 18320728
TI  - Trends in occupational asbestos exposure and asbestos consumption over recent
      decades in Korea.
AB  - In Korea, national statistics for asbestos exposure levels covering various
      asbestos industries and associated with specific years have never been published.
      The authors analyzed 2,089 asbestos exposure data sets compiled from 1995 through
      2006. Exposure levels were characterized according to type of asbestos industry
      and year. Asbestos exposure levels have decreased over time, dropping sharply
      from 0.92 fibers/cc (f/cc) in 1996 to 0.60 f/cc in 1997, to 0.19 f/cc in 1998,
      and to 0.06 f/cc in 1999, possibly in part because of enforcement of 1997
      legislation banning the use of amosite and crocidolite. In particular, a
      substantial reduction in asbestos exposure levels was most evident among primary
      industries handling raw asbestos directly. A similar relationship was found
      between a significant decline in asbestos consumption volume and the timing of
      regulation enforcement.

PMID- 18320729
TI  - Pesticide-related dermatitis in Saku district, Japan, 1975-2000.
AB  - Cases of dermatitis caused by pesticide exposures (n = 394), tabulated by the
      Division of Dermatology, Saku Central Hospital, Japan, from 1975 to 2000 are
      described. Dermatitis cases gradually decreased from 1975 to 2000, presumably
      accelerated by the phase-out of dermatitis-causing pesticides, including
      difolatan fungicide and salithion, an organophosphorous insecticide. Cases of
      chronic and solar dermatitides gradually decreased, which may be explained by
      reductions in the use of allergenic or photosensitive sulfur agents and
      organophosphates. However, the ratios of chemical burns from irritant pesticides-
      calcium polysulfide, dazomet, methyl bromide, chlorpicrin, paraqat/diquat,
      organophosphorus, quintozene, and glyphosate--rose in those years. Chemical burns
      from calcium polysulfide were responsible for most of the severe cases.

PMID- 18320730
TI  - Occupational injuries reported in a population-based injury survey in Vietnam.
AB  - This analysis of data from the Household Injury Survey conducted in Viet Nam in
      2004-2005 sought to characterize the patterns of work-related injuries in Viet
      Nam and to determine whether self-employed and artisanal workers had higher rates
      of injuries than formally employed workers. The annual incidence rate of work
      related injuries in Viet Nam was 7.06 per 1,000 person-years. Daily alcohol
      consumption was strongly associated with work-related injuries. The highest
      burden of injuries was among farmers. Mechanical forces were the most common
      mechanism of injury. Self-employed workers had a rate of work-related injuries
      26% higher than that of formally employed workers. Self-employed workers were
      younger, less educated, and more likely to be male. This population-based survey
      showed substantial underreporting of occupational injuries by existing
      surveillance mechanisms, which focus on formally employed workers. Priorities for
      future work include developing an integrated surveillance system for injuries and
      implementing further needs assessments to improve the prevention of occupational
      injuries.

PMID- 18320731
TI  - Suicide and occupation in New Zealand, 2001-2005.
AB  - Emerging evidence for the role of occupation in suicide risk prompted this
      analysis. All suicide records in New Zealand between 2001 and 2005 were reviewed.
      Age- and sex-adjusted suicide rates were calculated for nine major occupational
      groups. Rates for those not in paid work were adjusted for sex only. A total of
      2,024 suicide cases were reviewed. People engaged in paid work had one-fourth of
      the suicide rate of the non-waged (p < 0.005). Those working in farming,
      fisheries, or forestry and trades had higher suicide rates than people in other
      occupations. Homemakers and people with office jobs had the lowest suicide rates.
      Occupation influenced suicide rates. The continuing disparity in suicide rates
      between non-waged and waged workers is of particular concern and needs to be
      addressed. Farmers and trades workers should be monitored more closely.

PMID- 18320732
TI  - A web- and case-based learning program for postgraduate students in occupational
      medicine.
AB  - Many Belgian postgraduate students in occupational medicine already work in the
      field although they have had little training or experience. To direct their
      learning in line with professional needs, an interactive web-based program was
      developed and evaluated. On-line multiple-choice questions and real-life cases
      were used as an add-on to the master course in occupational medicine. Students'
      perceptions were obtained by questionnaire. Trainees felt that the multiple
      choice questions with immediate feedback and automatic scoring increased their
      factual knowledge. The case studies were well received because they were
      realistic and of appropriate difficulty level. Students preferred the combination
      of face-to-face teaching and e-learning to a whole course online and were in
      favor of more active communication between teachers and users. These findings may
      inform further collaborative developments in educational technology in
      occupational health.

PMID- 18320733
TI  - The defence of chrysotile, 1912-2007.
AB  - The commercial exploitation of asbestos may be dated from the late 1870s, when
      Canada was the major world source. Reports of severe and fatal respiratory
      disease in workers in asbestos factories appeared in Britain (1898, 1906), and in
      France (1906) and Italy (1908). In 1912 the Canadian Department of Labour denied
      that the health of Quebec's millers and miners was affected. A series of denials
      appeared for over 40 years, until in 1955 a Thetford Mines medical officer
      reported finding that between 1945 and 1953, among some 4,000 asbestos workers
      128 had asbestosis of various degrees of severity, 121 diagnosed
      radiographically, and 33 confirmed at autopsy. Although a committee of inquiry
      into health in the asbestos industry (1976), and a Royal Commission on health and
      safety arising in the use of asbestos in Ontario (1984) confirmed that disease
      had occurred, these findings were to have no adverse effects on asbestos exports.
      Rather, the inquiries constituted elements in the industry's successful public
      relations exercise that continues to operate to this day. Even when an increasing
      number of national bodies have legislated for total bans on asbestos use, a
      policy with which all the international bodies concerned with public health
      agree, the Canadian PR apparatus continues to be able to call on physicians and
      scientists prepared to oppose the consensuses reached by the independent advisors
      to these bodies.

PMID- 18320734
TI  - Yokohama declaration for fair and equal compensation for all asbestos victims and
      their families.

PMID- 18320735
TI  - A moral history of the evolution of a caste of doctors: the issue of trust and
      the public health model.

PMID- 18320736
TI  - ACOEM denies industry partisanship.

PMID- 18320737
TI  - Industry influence on IAOH.

PMID- 18320738
TI  - [Non-insulin treated diabetes: relationship between disease management and
      quality of care. The Entred study, 2001].
AB  - INTRODUCTION: We studied the relationship between 100% medical fee coverage for
      chronic disease and quality of care in people with type 2 diabetes treated with
      oral hypoglycaemic agents (OHA) only, in France. METHODS: For the Entred study,
      10,000 adults who received reimbursements for a delivery of OHA or insulin were
      randomly sampled from the database of the major national medical insurance system
      in 2001. For these 10,000 people, we extracted all medical consumption from the
      2001 database and mailed a medical questionnaire; another questionnaire was
      mailed to their medical provider. We restricted the analysis to people with type
      2 diabetes, treated with OHA only, with no annual visit to an endocrinologist (n
      = 1167), and to a sub-group with no complication reported by their medical
      provider (n = 525). RESULTS: 71% of people benefited from a waiver of co-payment
      due to a chronic disease (100% medical fee coverage for a list of 30 diseases
      including diabetes). People with 100% coverage were more likely to be women,
      older, with a longer duration of the disease, more often on several OHA and a
      drug for cardiovascular disease, and had a higher level of HbA1c. In multivariate
      analyses, 100% fee coverage was linked with a higher frequency of three HbA1c
      measurements (OR = 2,5 [1,6-4,0]), one electrocardiogram (1,9 [1,2-3,1]) and one
      podiatric visit (2,2 [1,1-4,3]) in 2001 in people without complications. No
      association was found with one measurement of albuminuria, creatininemia, lipids,
      and ophtalmological, dental or dietitian visit. CONCLUSIONS: In 2001, a
      significant relationship was found between 100% medical fee coverage on a better
      quality of care for people with diabetes on OHA at an early stage of the disease.
      Several explanations are further discussed.

PMID- 18320739
TI  - [Hereditary spherocytosis].

PMID- 18320740
TI  - [Interstitial lung disease. More accurate diagnosis and an uncertain prognosis].

PMID- 18320741
TI  - [Mechanisms in pulmonary fibrosis].
AB  - Despite the continuous and renewed interest in IPF, the precise biological
      mechanisms underlying the development of fibrosis and leading to the irreversible
      destruction of the lung are still unknown. Inflammation seems to play a minor
      role at the initiation of the disease. Identification of excessive apoptosis of
      alveolar epithelial cells led to the hypothesis that the disorder results from
      repeated alveolar epithelial cell injury and activation. In turn, alveolar
      epithelial cells induce the recruitment, proliferation, and activation of
      mesenchymal cells with the formation of fibroblastic foci and the abnormal
      accumulation of extracellular matrix. Fibroblastic foci are connected in a
      tridimensional reticulum. Circulating mesenchymal precursors called fibrocytes,
      and transdifferenciation of epithelial cells, endothelial cells and/or
      mesothelial cells, may all contribute to the accumulation of fibroblasts in the
      lung.

PMID- 18320742
TI  - [Idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF) is currently defined by a set of
      histopathological-radiological-clinical criteria including an histopathological
      pattern of usual interstitial pneumonia, reticular opacities with honeycombing at
      tomodensitometry, progressive exercise dyspnea in a patient older than 60 years
      with fine crackles at lung bases at auscultation. The incidence of IPF is
      increasing. Risk factors for the disease have been identified (smoking, exposure
      to various dusts, genetic polymorphism) but the true cause of FPI remains
      unknown. Progression to death within 2-4 years may be accelerated by acute
      exacerbation which may cause death. There is no efficient treatment for IPF.
      Corticosteroids and immunosuppressors are of no benefit. Therapeutic trials are
      on the way.

PMID- 18320743
TI  - [Interstitial lung disease in connective tissue diseases].
AB  - Interstitial lung disease (ILD) may occur in the connective tissue diseases, with
      a negative impact on survival. The diagnosis of ILD is established by crackles of
      the lung bases at auscultation, and high resolution computed tomography of the
      chest demonstrating diffuse opacities predominating in the bases (ground glass
      opacities, reticular opacities, honeycombing, and traction bronchiectases).
      Bronchoalveolar lavage mostly contributes to the differential diagnosis. Video
      assisted thorascopic lung biospy is seldom required for clinical management.
      Clinically significant ILD occurs in 25% of patients with systemic sclerosis, 7
      30% in patients with dermatopolymyositis (especially with antisynthetase
      antibodies including anti-Jo-1 antibodies, often with a subacute onset), and 5%
      of patients with rheumatoid arthritis. Nonspecific interstitial pneumonia (with
      fibrosis) is the predominating histopathological pattern in systemic sclerosis
      and dermatopolymyositis; a pattern of usual interstitial pneumonia is frequent in
      rheumatoid arthritis (with a clinical and radiological presentation similar to
      that of idiopathic pulmonary fibrosis). ILD of various presentations may occur in
      Sjogren syndrome, possibly associated with thin-walled cysts; pulmonary lymphoma
      must be ruled out. Little information is available regarding treatment of ILD in
      connective tissue disease. Clinically modest short-term efficacy of
      cyclophosphamide treatment has been shown in systemic sclerosis, but was not
      maintained at 2 years.

PMID- 18320744
TI  - [Cryptogenic and secondary organizing pneumonia].
AB  - Organising pneumonia is an inflammatory and fibroproliferative reaction of the
      lung, which gives rise to a clinico-pathological syndrome. It may occur without
      any detectable cause (cryptogenic organising pneumonia) or may be associated with
      various processes such as infections, drug toxicities, connective tissue
      disorders, etc. (secondary organising pneumonia). The clinical picture is usually
      subacute and includes fever, fatigue, weight loss, cough, dyspnea, crackles, and
      elevated inflammatory markers. At imaging, the most typical pattern consists of
      multiple subpleural consolidations. Bronchoalveolar lavage reveals a mixed
      alveolitis with lymphocytes and polymorphonuclear cells. Lung biopsy shows buds
      of loose connective tissue filling the lung alveoli. The diagnosis is made by
      combination of clinical, imaging and histopathological criteria. Most patients
      respond very well to corticosteroid therapy. Relapses are common but can usually
      be controlled with moderate doses of prednisone, and do not worsen the prognosis.

PMID- 18320745
TI  - [Drug-induced lung diseases].
AB  - Drug-induced interstitial pneumonias are systematically considered in the
      differential diagnosis of the interstitial pneumonias. The presentation may be
      acute, sub-acute or chronic, with the same drug possibly leading to either acute
      or subacute/chronic interstitial lung disease (e.g. amiodarone). There is no
      definite diagnostic criterion, the final diagnosis relying on the clinical and
      imaging features, the chronology of pulmonary manifestations, and the prevalence
      of reported cases with the suspected drug.

PMID- 18320746
TI  - [Interstitial lung diseases in sarcoidosis].
AB  - Sarcoidosis is a multisystem disorder of unknown aetiology characterized by
      immune granuloma in involved tissue with predilection for lung and lymphoid
      system. The sarcoidosis aetiology remains unknown. It could result of genetic
      predisposition and exposure to specific enviromental factors. The chest X-ray is
      abnormal in 90% of cases with adenopathies and/or massive pulmonary infiltration
      with or without fibrosis. The different aspects are classified in 4 stages. The
      diagnosis is done when clinical and radiological usual signs are present with
      histological granuloma without caseum and in the absence of any other
      granulomatous disease. Most of the time, sarcoidosis spontaneously heals in 2 to
      3 years. 10 to 30% of cases are chronic and often more severe. The disease could
      lastly generate a pulmonary fibrosis with a potential respiratory insufficiency,
      cor pulmonale, or aspergillus infection. Cardiac, neurologic, throat, kidney or
      ophthalmologic lesions or hypercalcemia may also be of bad prognosis. Sarcoidosis
      is lethal in 0.5 to 5% of cases. Mild disease does not need to be treated.
      Systemic corticosteroid for 12 months at least is the treatment for more severe
      diseases. Antimalarials drugs and immunomodulatory agents may be used if
      corticosteroids cannot be used or failed. TNFalpha recently proposed is currently
      evaluated.

PMID- 18320747
TI  - [Occupational interstitial lung diseases].
AB  - Pneumoconioses are induced by the inhalation of mineral or metallic dust. The
      incidence has decreased in the industrialized countries, but these diseases still
      exist. Diseases diagnosed nowadays may result from exposures that date back
      several decades. Besides, industry continuously creates new types of exposure and
      produces novel materials and alloys. Unusual exposures, sometimes in small
      workshops or in independent workers, may still cause severe diseases. In case of
      exposure to some metals, like beryllium, diseases may occur in susceptible
      subjects even at low levels of exposure. Medical and social consequences of
      misdiagnosis may be important. The diagnostic contribution of high resolution
      computed tomography (HRCT) scan is very important, as this technique is sensitive
      and specific. Pathological, mineralogical, and immunological techniques are
      useful in the differential diagnosis. Hypersensitivity pneumonitis is a
      granulomatous interstitial disease of the lungs due to immune reactions following
      chronic inhalation of antigens, to which the subject has been previously
      sensitised. Diagnosis is based on associated clinical and paraclinical signs
      which are not specific. Clinical approach is essential. It allows to suspect the
      diagnosis in view of respiratory symptoms, inspiratory crackles and the
      identification of a hazardous environment. Serological tests, bronchoalveolar
      lavage and HRCT scan are required to confirm diagnosis. Early removal of exposure
      prevents the occurrence of chronic respiratory failure. Corticosteroids can be
      used in severe forms during few weeks.

PMID- 18320748
TI  - [Patient education handout. Fiber optic bronchoscopy and bronchoalveolar lavage].

PMID- 18320749
TI  - [The evolution of the physician].

PMID- 18320750
TI  - [Sinus infections of children and adults].

PMID- 18320751
TI  - [Edema of the lower limb].

PMID- 18320752
TI  - [Hemochromatosis].

PMID- 18320753
TI  - [Acute fever in an immunocompromised patient].

PMID- 18320754
TI  - [Crohn's disease and ulcerative colitis].

PMID- 18320755
TI  - [Partial facial transplantation. A surgical breakthrough].

PMID- 18320756
TI  - Incidence and pattern of presentation of dry socket following non-surgical tooth
      extraction.
AB  - OBJECTIVES: To determine the incidence and pattern of presentation of dry socket
      as a complication of intra-alveolar dental extraction at the Lagos University
      Teaching Hospital. METHODS: Patients who were referred for intra-alveolar dental
      extractions under local anaesthesia at the exodontia clinic of the Department of
      Oral and Maxillofacial Surgery of the Lagos University Teaching Hospital between
      July and December 2002 were included in the study. The following data were
      recorded for each patient: biodata, reason for extraction, number and type of
      teeth extracted, time taken for the extraction to be done, smoking habit, and use
      of oral contraceptives. Onset of symptoms and type of teeth involved for those
      with diagnosis of dry socket were also recorded. RESULTS: Thirty-one teeth (5.6%)
      of a total of 554 teeth extracted during the period of the study developed dry
      socket. The mean age (SD) of the 27 patients who developed dry socket was 32.2 +/
      13.0 years, (m; f ratio of 1: 4.4). Most (44.5%) of the patients who presented
      with dry socket were in the 3rd decade of life, with more than half (59%) of them
      presenting on the 3rd day following extraction. Mandibular and maxillary teeth
      were equally affected. Molars and premolars were exclusively affected. Difficulty
      of extraction was significantly associated with the development of dry socket
      (p<.05). CONCLUSION: The incidence of dry socket in our centre is similar to
      previous reports. Female patients were significantly affected. Difficulty of
      extraction was significantly associated with the development of dry socket. Non
      dressing treatment provided satisfactory relief of the symptoms and subsequent
      granulation of the socket.

PMID- 18320757
TI  - Community pharmacies as possible centres for routine immunization.
AB  - BACKGROUND: Nigeria has embraced the primary healthcare movement and has
      committed its resources to the provision of cost effective community based
      primary healthcare strategy which recognizes the need for effective partnership
      between public and private sector. Immunizations are important part of this
      effort, especially the provision of the vaccines incorporated into the national
      Expanded Programme on Immunization (EPI) which has now metamorphosis to National
      Programme on Immunization (NPI) due to decline in immunization coverage.
      Community pharmacies can be involved in immunization to improve coverage as has
      been shown in the United States of America (U.S.A) that this led to great
      improvement in immunization coverage. The need to find out if this can also be
      adopted in Nigeria is the objective of this work. OBJECTIVES: This study
      therefore aimed to have an insight into current interest of community pharmacists
      to be involved in routine immunization and assess their physical structures for
      possible adaptation for use in routine immunization. METHOD: Sixty (60) pre
      tested questionnaires were randomly administered to community pharmacists. Forty
      three (43) questionnaires were retrieved for analysis. RESULTS: The study
      revealed that the use of community pharmacies as places where routine
      immunization services can be provided is feasible as shown by 95.3% interest
      expressed by community pharmacists. Most of the required infrastructures to carry
      out these services are on the ground as shown by availability of adequate space
      (88.4%), stand-by generator (83.7%) and functional fridge/ freezer (95.3%).
      Community pharmacists (88.4%) expect to be remunerated for providing this
      service. CONCLUSION: This study has shown the willingness of community
      pharmacists to participate in immunization efforts and the possibility of using
      pharmacies in routine immunization.

PMID- 18320758
TI  - Keloid and hypertrophic scars: a review of recent developments in pathogenesis
      and management.
AB  - AIM: The treatment of keloid and hypertrophic scars remains a challenging
      clinical problem despite numerous proposed therapies reported in the literature.
      This is due to the fact that the mechanisms that bring about keloid/hypertrophic
      scars are not completely understood. This article reviews the pertinent
      literature regarding the pathophysiology and management of keloid and
      hypertrophic scars. MATERIAL AND METHODS: A computerized literature search using
      MEDLINE was conducted for published articles on keloid and hypertrophic scars.
      The medical subject headings "keloid" or "hypertrophic scar" were combined with
      "treatment" or "management" or "mechanisms" or "pathophysiology" using the
      Boolean operator "AND" to narrow the searches. A review of selected relevant
      literature was undertaken. RESULTS: Numerous advances have been made in
      understanding the process of formation of wound healing and scar formation. This
      increased knowledge has led to the introduction of new treatments as well as to a
      better understanding of how older treatments work. These include surgical
      excision, intralesional steroid injection, cryotherapy, laser therapy,
      irradiation, mechanical compression dressing, silicone sheet applications,
      intralesional interferon injection, or combination of techniques. Many of the
      treatment modalities have a defined biologic basis while others are based on
      anecdotal reports. CONCLUSIONS: Presently there is still no single, reliable and
      effective treatment protocol for keloid and hypertrophic scars. However, surgical
      excision followed by postoperative intralesional steroid injection seems to
      provide a reasonable treatment outcome with low recurrence rate.

PMID- 18320759
TI  - Pattern of extremity gunshot injuries seen in Lagos University Teaching Hospital,
      Lagos, Nigeria.
AB  - BACKGROUND: The rising incidence of gunshot injuries (GSI) remains one of the
      leading causes of death, long hospitalization and economic losses worldwide. This
      study was undertaken due to rising incidence of civilian GSI in Lagos, Nigeria.
      OBJECTIVE: To determine the epidemiological characteristics of extremity gunshot
      injuries in Lagos, Nigeria. METHODS: This three year crossectional study of
      extremity gunshot injuries was conducted at the Lagos University Teaching
      Hospital (LUTH), Lagos, Nigeria between 1st January 2000 and 31st December 2002.
      RESULTS: Two hundred and fifty four patients with extremity gunshot injuries
      presented with 240 analyzed. Those brought in dead (BID) were excluded from the
      study. Ninety-five percent of the patients were males. One hundred and twenty six
      patients (52.5%) were in the 21-40 years age group. The patients were shot mainly
      (75%) at night and mostly (80%) by armed robbers. Shot guns were used in shooting
      47.5% of patients. CONCLUSION: The study showed that young adult males were more
      affected by GSI. Most of the shootings occurred at night by armed robbers.

PMID- 18320760
TI  - Uses and limitations of fine needles aspiration cytology in the diagnostic work
      up of patients with superficial lymphadenopathy.
AB  - Lymph node fine needle aspirations in 93 patients were studied to ascertain the
      usefulness of FNA cytology in determining the therapeutic approach. Cytologic
      results were compared with histologic diagnoses in 35 cases that underwent both
      aspiration and excisional biopsy. The cases with histological diagnoses included
      17 (28.3%) of the 60 cytologically benign cases, 6 (75.0%) of the 8 cytologically
      suspicious cases, 10 (55.5%) of the 18 cytologically malignant cases and 2
      (28.6%) of the 7 cytologically unsatisfactory cases. FNA in the present series
      showed a sensitivity of 90.0 per cent and specificity of 82.3 percent. It is
      concluded from this data that FNA can be an accurate, inexpensive and quick
      method of initial diagnosis in superficial lymphadenopathy.

PMID- 18320761
TI  - Lipid peroxidation and erythrocyte fragility in poorly controlled type 2 diabetes
      mellitus.
AB  - BACKGROUND: Type 2 Diabetes mellitus has been recently found to have evidence of
      raised inflammatory markers. The chronic inflammation correlates strongly with
      cardiovascular morbidity markers such as coronary artery disease, stroke and
      peripheral arterial disease. The chronic inflammation has been linked to the
      generation of free radicals. The evidence is however inconclusive. Thus there is
      increased interest in determining the oxidative status of persons with diabetes.
      OBJECTIVES: This study was carried out to determine if the plasma oxidative
      stress status is high in diabetics (especially those that are poorly controlled)
      and to determine the effect on erythrocyte stability. METHODS: Plasma levels of
      thiobarbituric acid reacting substances (TBARS), an index of lipid peroxidation,
      and erythrocyte osmotic stability were determined. These were compared between
      poorly controlled type 2 diabetics and nondiabetic individuals. RESULTS: The
      plasma level of TBARS were significantly higher in the plasma of the diabetics:
      0.90 +/- 0.09 micromol malondialdehyde (MDA) equivalent L(-1) vs 0.57 +/- 0.02
      micromol MDA equivalent L(-1) for control subjects (p=0.002). The diabetic
      erythrocytes also showed significantly higher fragility: 3.99 +/- 0.37%
      haemolysis vs 2.11 +/- 0.27% haemolysis for controls (p=0.0004). CONCLUSION: Our
      data shows the occurrence of significantly higher oxidative stress level and
      osmotic fragility of erythrocytes in the cohort of persons with poorly controlled
      diabetes mellitus.

PMID- 18320762
TI  - Pattern of paediatric malignancies seen at the Radiotherapy Department of the
      University College Hospital, Ibadan, Nigeria.
AB  - BACKGROUND: Paediatric tumours are seen by the radiotherapist following referral
      from other specialists. Patients seen by the radiotherapists may not conform to
      the full spectrum seen in the hospital. OBJECTIVE: To review the pattern of
      presentation of paediatric malignancies seen at the radiotherapy department of
      the UCH, Ibadan. METHODS: Retrospective study of all patients below the age of 12
      seen in Radiotherapy Department of UCH, Ibadan over a 19-year period was
      undertaken. Data were collected from the case files and the radiotherapy
      treatment cards. RESULTS: 244 cases were evaluated with age ranged between 4
      months and 12 years. Male to female ratio was 1.15 to 1.0. 23 tumour types were
      seen with retinoblastoma accounting for about 45% of all the patients reviewed.
      Burkitt's lymphoma accounted for only about 2.5%. CONCLUSION: Retinoblastoma,
      nephroblastoma, intracranial malignancies and rhabdomyosarcoma are the tumours
      most commonly seen at the Radiotherapy Department of the UCH, Ibadan.

PMID- 18320763
TI  - Oral metformin-ascorbic acid co-administration ameliorates alcohol-induced
      hepatotoxicity in rats.
AB  - BACKGROUND: Alcoholic liver disease remains a major cause of liver failure
      worldwide with no available curative or prophylactic therapy as at present. High
      dose metformin is reported to ameliorate liver injuries in both human and animal
      models of acute and chronic alcoholic liver injuries. OBJECTIVES: The aim of the
      present in vivo animal study was to determine whether metformin-ascorbic acid co
      administration also prevents alcoholic hepatotoxicity in chronic alcohol
      exposure. METHODS: In the present study, ameliorating effect of 200 mg/ kg/day of
      ascorbic acid (Asc), 500 mg/kg/day of metformin (Met) and their co-administration
      (Met-Asc) were investigated in 5 groups of 50% ethanol-treated male Wistar rats
      for 2 weeks of the experiment. The body weight of each rat was taken on days 1,
      7, and 14 of the experiment, respectively. On day 15, fasted blood samples for
      plasma lipids and liver enzyme markers were collected via cardiac puncture from
      the rats under diethyl ether anaesthesia. RESULTS: Results showed that
      administration of graded oral doses of 50% ethanol for 14 days significantly
      (p<0.001) elevated the plasma liver enzymes--aspartate aminotransferase (AST),
      alanine aminotansferase (ALT) and alkaline phosphatase (ALP). Two weeks of
      ethanol treatment also induced alterations in the plasma triglycerides (PTG),
      total cholesterol (PTC), high density lipoprotein (HDL-c), and low density
      lipoprotein (LDL-c). However, these elevations were significantly (p<0.05)
      attenuated by Asc, Met, and Met-Asc after 14 days of oral treatment, with Met-Asc
      having higher significant (p<0.001) ameliorating effect than Asc alone but with
      comparative effect to that of Met alone. CONCLUSION: High dose metformin-ascorbic
      acid co-administration protected the liver against the deleterious effects of
      chronic high dose alcohol and the hepatoprotective effect of Met-Asc appeared to
      be due mainly to the metformin molecule of the drug combination. However, further
      studies would be required to evaluate the mechanisms underlying the observed
      effects.

PMID- 18320764
TI  - Routine patch testing in a dermatology clinic of a teaching hospital in Nigeria.
AB  - INTRODUCTION: Allergic Contact Dermatitis (ACD) poses a great diagnostic
      challenge to the dermatologist as it mimics many common dermatoses. Patch test
      (PT) is used to establish the diagnosis of ACD and to exclude suspected
      allergens. AIM: This study reviewed the clinical presentations and patch test
      results of consecutive patients with the diagnosis of allergic contact dermatitis
      seen at the skin clinic of the Lagos University Teaching Hospital (LUTH).
      METHODS: This was a prospective study of all patients that presented with
      features of allergic contact dermatitis at the skin clinic of LUTH between
      September 2003 and October 2004. One hundred and two patients with ACD and 100
      controls were patch tested and included in the sample size. RESULTS: Allergic
      contact dermatitis accounted for 7.7% of patients that presented at the
      dermatology clinic of LUTH during the study period. There was a slight female
      preponderance and the highest number of patients presented between the ages of 21
      and 40. Features of chronic eczema were found in 71.4% of patients. Sixty
      patients (58.3%) and 26 controls (26%) had positive patch test responses. There
      was a statistically significant difference between the patch test responses in
      patients and controls. The specificity of the patch test procedure was 74% and
      the sensitivity was 58.8%. CONCLUSION: Patients with allergic contact dermatitis
      will benefit from routine patch test for aetiological diagnosis and to prevent
      chronicity.

PMID- 18320765
TI  - Evidence-based dental practice: part III. Critical appraisal of the literature,
      relevance and application of the evidence.
AB  - Evidence-based dentistry involves defining a question focused on a patient
      related problem and searching for reliable evidence to provide an answer. Once
      potential evidence has been found, it is necessary to determine whether the
      information is credible and whether it is useful in one's practice by using the
      technique of critical appraisal. This article discusses the guidelines that have
      been developed to guide clinicians in assessing the validity and the relevance of
      published studies (randomized control trials, systematic reviews, cohort studies
      and case-control studies). The concept and tools of "critical appraisal" of
      published research works were developed by the evidence-based medicine group at
      McMaster University, Canada.

PMID- 18320766
TI  - [True or false mental disorders? ].

PMID- 18320767
TI  - [Management of severe antepartum depression: an update].
AB  - We update the epidemiology, diagnostic process, significant clinical features as
      well as main treatment and prevention issues in the field of antepartum
      depression, a widespread condition with significant relevance to primary care.
      During pregnancy, one forth women exhibit clinical symptoms of depression and
      such maternal depression may have disruptive effects on infants attachment
      process, marital relationships, family cohesion and work adjustment. Strenghts
      and limitations of psychotherapy, antidepressant medication and psychiatric
      hospitalisation are reviewed with a special accent on the specific ethical and
      scientific issues associated with the clinical dilemma of risks balance
      evaluation and medication treatment choice with these patients.

PMID- 18320768
TI  - [Stalking: a new traumatic syndrome?].
AB  - Stalking is a recently described syndrome including a pattern of repeated
      intrusion and seeking for intimate relationship with another person that is
      unwanted. Such behaviour is perceived as an explicit threat from a victim who
      experiences fear. Recent studies indicate that stalking is an important legal and
      clinical issue with elevated prevalence rates especially among women (10%)
      eventually with dramatic consequences. Furthermore stalking situation are
      important in psychiatric practice especially among patients referred to emergency
      room and crisis intervention. A specific form of "treatment barrier" comes along
      with stalking and will be discussed. Judiciary actions are often necessary before
      it is possible to plan a treatment.

PMID- 18320769
TI  - [Panic disorders: differential diagnosis and care in emergencies].
AB  - Despite the high prevalence of panic disorders in patients in primary-care
      settings, this condition is frequently under-recognised and under-treated. After
      the description of DSM-IV diagnosis criteria of panic disorders, this paper
      underline the importance of an adequate somatic and psychiatric differential
      diagnosis. Even if cognitive-behavioural therapy is the best studied
      psychotherapeutical approach, several efficacious psychodynamic psychotherapies
      were also described. High-potency benzodiazepines provide a rapid efficacy with
      beneficial effects during the first days of treatment. However, benzodiazepines
      should be avoided in the long term, because of the development of tolerance and
      dependence. Antidepressants (SSRI, venlafaxine) are effective in preventing panic
      attacks, especially in improving anticipatory anxiety and avoidance behaviour.

PMID- 18320771
TI  - [Dissociative disorders: neurologists and psychiatrists working together].
AB  - Dissociative disorders often have an atypical neurological presentation requiring
      a complex diagnostic process at the interface between neurology and psychiatry. A
      strong interdisciplinary collaboration is needed for diagnosis restitution and
      patient treatment. Current knowledge is still scarce but recent studies in
      clinical neuroscience enrich this field. This article presents the main aspects
      of dissociative disorders and suggests a treatment framework.

PMID- 18320772
TI  - [How do we begin a medical interview? Reflections from videotapes].
AB  - The medical interview consists of several steps, each consisting of specific
      tasks and objectives for the doctor. The initial step of the medical
      consultation, the social phase, is the cornerstone in the construction of a
      doctor-patient relationship of trust and quality. If, in a structural point of
      view, the literature has responded in a clear and consistent way, questions
      remain openned in a procedural point of view. How successful is the physician to
      establish the first contact? How does he proceed to welcome his patient? We
      looked out ways to address these issues by the work of revising the video
      recordings of general medical consultations, which are regularly practiced at the
      Medical outpatient clinic of the University of Lausanne.

PMID- 18320773
TI  - [Stress in health care workers].
AB  - A growing body of evidence indicates that health care professionals are in need
      of support. Beside heavy clinical patient volume or administrative duties, stress
      related to the significance of contextual factors is an important source of
      clinician's distress. Identification of and working through such stress can be a
      durable source of support. This article discusses key elements of these
      stressors, namely, the role of emotions of the clinician, awareness of limits,
      confusion about empathy, the influence of development and life trajectory on
      professional identity and the conflicting roles of the health care provider being
      in need of support.

PMID- 18320774
TI  - [Development and application of the passive smoking monitor MoNIC].
AB  - A passive sampling device, called Monitor of NICotine (MoNIC), was constructed
      and evaluated by the laboratory of the Institute for Work and Health to determine
      nicotine in Environmental Tobacco Smoke (ETS). To support a large campaign on the
      subject of passive smoking, the CIPRET Valais gracefully distributed more than
      1500 MoNIC badges to the Swiss population in order to measure ETS. Non-stimulated
      saliva was also collected to determine nicotine/cotinine levels of participating
      volunteers. The inhaled Cigarette Equivalents (CE) by non-smokers was calculated
      for non-smokers, based on a reference of 0.2 mg of nicotine per cigarette. Using
      the detected CE on the badge for non-smokers, and comparing it to the
      nicotine/cotinine levels in saliva, we could confirm the use of the CE concept
      for estimating exposure to ETS.

PMID- 18320775
TI  - [Prasugrel versus clopidogrel. From the American Heart Association meeting,
      2007].

PMID- 18320776
TI  - [Wegener granulomatosis].

PMID- 18320777
TI  - [Hepatitis B: a controversy for the French].

PMID- 18320779
TI  - [Saying goodbye to world records].

PMID- 18320778
TI  - [Should we place babies in front of the television? (2)].

PMID- 18320780
TI  - [What I think of managed care (5)].

PMID- 18320781
TI  - [The rise of the irrational].

PMID- 18320782
TI  - Calcium and vitamin D for osteoporotic fracture prevention.

PMID- 18320783
TI  - Did we really need another comparison of warfarin with aspirin? An assessment of
      the BAFTA trial.

PMID- 18320784
TI  - Magnesium in the acute management of atrial fibrillation: noise or music?

PMID- 18320785
TI  - Should all women be vaccinated against HPV?

PMID- 18320786
TI  - "White coat hypertension" in type 2 diabetic patients.
AB  - INTRODUCTION: "White coat hypertension" is a phenomenon in which patients exhibit
      elevated blood pressure in clinical setting, but not recorded by themselves at
      home. OBJECTIVES: The aim of this study was to evaluate frequency of "white coat
      hypertension" in type 2 diabetic patients, in which high blood pressure values in
      clinical setting were observed for the first time. PATIENTS AND METHODS: The
      study comprised 52 type 2 diabetic patients with newly diagnosed high blood
      pressure values in measurements with the use of mercurial sphygmomanometer during
      ambulatory visit (mean "office blood pressure" values > or =140/90 mmHg). In all
      patients ambulatory blood pressure measurements (ABPM) were conducted. "White
      coat hypertension" was detected when the mean blood pressure value in ABPM during
      the day was <135/85 mmHg and the mean "office blood pressure" was > or =140/90
      mmHg. Arterial hypertension was detected when the mean "office blood pressure"
      values were > or =140/90 mmHg and the mean blood pressure value in ABPM during
      the day were > or =135/85 mmHg. RESULTS: In forty-four percent of the studied
      patients "white coat hypertension" was diagnosed (group 1). Group 2 consisted of
      patients with arterial hypertension (56% of all studied patients). Blood pressure
      values estimated on the ambulatory basis with the use of ABPM were lower in group
      1 than in group 2 (p <0.05). There were no differences between the study groups
      in blood pressure values estimated by traditional method with the use of
      mercurial sphygmomanometer during clinic visit (p >0.05). CONCLUSIONS: In above
      2/5 of type 2 diabetic patients with newly detected high blood pressure during
      clinic visits, "white coat hypertension" was diagnosed.

PMID- 18320787
TI  - Components of metabolic syndrome in women after gestational diabetes.
AB  - OBJECTIVES: The aim of the study was to evaluate the risk of occurrence of
      metabolic syndrome (MS) in females who suffered from gestational diabetes
      mellitus (GDM). PATIENTS AND METHODS: 495 letters were sent to patients with a
      history of GDM treated in the Department between 1993-2002. One hundred and fifty
      three (30.9%) patients who responded positively formed the study group. Out of
      them 74 had already been treated for diabetes mellitus, and glucose intolerance
      was found in 5 subjects. Seventy-four patients had been subjected to a 75 g Oral
      Glucose Tolerance Test, as well as the control group that consisted of 155
      subjects, in whom GDM during pregnancy was excluded. In all patients lipid
      parameters, blood pressure, height, weight and waist circumference were measured
      and body mass index (BMI) was calculated. Metabolic syndrome was diagnosed
      according to the modified NCEP-ATP III criteria from 2005 (3 of 5 had to be
      fulfilled). RESULTS: Patients from the study group were older than from the
      control group (p <0.05), higher was their BMI at the time of the index pregnancy,
      as well as after the observation time (p <0.0001). Metabolic syndrome was
      developed in 47 (30.7%) patients of the study group and 8 (5.2%) patients from
      the control group (p <0.001). The study group presented all components of MS
      significantly more often than the control group--in both groups, we found
      respectively: abnormal waist circumference--57% vs. 37.6% (p <0.005),
      hypertension--18.9% vs. 1.9% (p <0.001), elevated fasting glycemia--79.1% vs.
      1.9%, hypertriglyceridemia--21.6% vs. 2.6% (p <0.0001), and decreased
      concentrations of high-density lipoprotein cholesterol--11.1% vs. 2.6% (p
      <0.005). CONCLUSIONS: Patients who suffered from GDM are at high risk for
      carbohydrate disturbances and metabolic syndrome in the following year.
      Therefore, they should be under continuous medical surveillance that would enable
      early detection and treatment of the metabolic disturbances.

PMID- 18320788
TI  - [Influenza and flu prophylaxis--a current medical issue].
AB  - Influenza is a disease which returns every epidemic season in different degrees
      of severity, especially in high-risk groups. According to current data, 5-25% of
      the world population contract this disease and mortality because of influenza
      reaches 0.5-1 million people. However, this problem is still not dealt with
      appropriately and is even disregarded. In contrast to other viruses influenza
      cannot be eradicatedas a result of its changeability but post-influenza
      complications can be dealt with using prophylactic methods. Since 9 May 1977
      there have been more and more fatal cases of human infections with bird flu. The
      danger of another outburst of a flu pandemic is imminent. According to World
      Health Organisation influenza is one of the priorities of public health--that is
      the reason of originating International Influenza Surveillance Programme. A basic
      method of protecting the population against influenza, which is also the
      cheapest, is vaccination of as many people in the population as possible,
      especially those from high-risk groups. Post-influenza complications result not
      only in illness but also in economic losses.

PMID- 18320789
TI  - [Untypical cause of heart failure--right atrial myxoma].
AB  - The study presents case of a 62-year-old female patient with symptoms of the
      heart failure NYHA class III intensifying for the last 2 months. In the physical
      examination at admission no significant abnormalities were found. In the two- and
      three-dimensional echocardiography normal thickness and contractility of the left
      ventricle wall were found, as well as the normal systolic function of the right
      ventricle. In enlarged right atrium a structure of the oval shape was found with
      the features of continuity with atrial septum and bulging of a small part of the
      structure through the orifice of the tricuspid valve to the right ventricle. In
      the study no features of blocking the tricuspid flow or the inflow from the main
      veins and coronary sinus were detected. On the basis of the complete
      echocardiographic examination and clinical presentation tentative diagnosis of
      right atrium myxoma was made. In coronary angiography no significant
      abnormalities in coronary arteries were found. After cardio-surgical consultation
      the patient was scheduled for the surgical removal of the tumor, which was
      performed without complications. The histopathological examination confirmed the
      diagnosis of myxoma. In the follow-up echocardiography carried out after 8 months
      the reduction of the cavity of the right atrium was found and a good function of
      the ventricles. There were no features of the tumor re-growth.

PMID- 18320790
TI  - [Is every case of muscle damage during hypolipemic therapy the side effect of
      this therapy? A case report].
AB  - Hypolipemic agents, both statins and fibrates, may cause a spectrum of side
      effects, including the transient increase in creatine phosphokinase (CPK)
      activity. Muscle injury may present as common myalgia, non-specific myositis with
      normal CPK levels, myopathy and in the most serious cases, as rhabdomyolysis.
      Muscle damage is much more probably in patients with concomittant kidney and
      liver diseases, hypothyroidism, and serious infections or after some injuries or
      a heavy physical effort. On the other hand, one of the most common causes of
      secondary hypercholesterolemia and myopathy is hypothyroidism. This condition,
      which may enhance the risk of muscle damage in the course of hypolipemic
      treatment, may sometimes present with an atypical clinical presentation, making
      its diagnosis challenging. In this article, we present the case of a 50-year-old
      male physical worker presented with marked dyslipidemia, in whom myopathy was
      diagnosed during therapy with hypolipemic agents. Cessation of the treatment
      resulted in the only moderate reduction of CPK activity. Only just the
      introduction of thyroid hormone supplementation led to regression of symptoms and
      normalization of abnormalities found in laboratory examinations including
      remarkable improvement in lipid profile. After several months of observation we
      consider that hypolipemic treatment probably revealed previously occult
      autoimmune thyroid disease in this patient.

PMID- 18320791
TI  - [Stanislaw Kopczynski, a specialist in internal medicine and neurology--pioneer
      of school sanitary sciences in Poland].
AB  - The beginnings of school hygiene are connected with the work of dr Stanislaw
      Kopczynski (1873-1933), specilist in internal medicine and neurologist, who after
      the First World War organised hygenic and medical care in schools all over the
      country.

PMID- 18320792
TI  - [Analysis of the national tuberculosis program. Evolution of tuberculosis in
      Bihor district, Romania].
AB  - The prevention and control of tuberculosis are made by a special network,
      covering all the sanitary units and the entire medical staff. Ten years ago, the
      DOTS strategy (Directly Observed Treatment, Short-course) was enacted and the
      National Program for tuberculosis control (PNCT) was implemented on "medium
      terms" (1997-2000 and after that 2001-2005), with results in 2003 when, for the
      first time after two decades, has been observed a decrease of the incidence of
      tuberculosis, maintained also during the next years. The national program of
      health - the Supervising and control of tuberculosis, in Bihor district rolled in
      good terms, without any problems in achieving the proposed aims, due to the good
      coordination between institutions and professionals directly involved in the
      surveillance and control of disease. As a result of PNCT and prophylactic
      programs, there was a long-term diminish of costs associated to health care and a
      medium-term improvement of the following variables: incidence, mortality caused
      by TB, rate of readmissions, rate of therapeutic success of new TB cases with
      positive microscopy / new culture-positive TB cases, rate of diagnosis of new
      pulmonary TB cases with positive microscopy.

PMID- 18320793
TI  - [Experimental model of in vitro generation of human dendritic cells].
AB  - INTRODUCTION: Dendritic cells (DCs) are considered the most powerful antigen
      presenting cells (APC) playing a strategic role in triggering the immune
      response. Monocytes are the physiological precursors of myeloid DCs. AIMS: This
      paper aims to develop an in vitro experimental model of human dendritic cells
      generation and phenotypic and functional analysis starting from CD14+ monocyte
      precursors isolated from peripheral blood. MATERIALS AND METHODS: CD14+ monocytes
      were isolated from venous peripheral blood which was harvested from consenting
      healthy donors. By the means of GM-CSF and IL-4 immature DCs were generated from
      monocytes. In the sixth day we added TNF-alpha and PGE-2 maturation factors and,
      after 48 hours we harvested mature DCs. Their morphology was monitored by optical
      microscopy, while the phenotypes were determined by flow cytometry. RESULTS:
      After three days of culture, the monocytes developed a specific morphology,
      gathering in clusters; cells presenting specific features start to detach in the
      sixth day. Treatment with TNF-alpha and PGE-2 induces the maturation of DCs and
      up-regulation of CD80, CD83 and CD86 expressions. Phenotypic analysis of mature
      DCs was HLA-DR+++/CD86- CD80+++/CD14(-)/CD11a+/CD83+++. DCs obtained are able to
      stimulate in vivo allolymphocyte capacity. Functional analysis test showed 87%
      CD4+ CFSE+(DCs+PBMC) cells vs CD4+ CFSE+(PBMC) 15% cells. CONCLUSIONS: This
      experiment developed an effective and viable way to generate DCs from PBMCs
      exposed to GM-CSF and IL-4. The cells obtained presented morphological,
      phenotypic and functional features as DCs described in the literature.

PMID- 18320794
TI  - [Diagnostic, therapeutic and prognostic significance of sternal fractures].
AB  - This paper is a retrospective study based on a group of 62 patients with sternal
      fractures (SF), selected from a group of 637 patients presented in our unit with
      thoracic trauma between 1997 and 2004. The aim of this study is to evaluate SF
      from the epidemiological, etiopathogenic, diagnostic and therapeutic point of
      view. The incidence of SF was 12.24%. We studied two subgroups, differentiated by
      SF morphology and therapeutic approach: first group of 24 patients with complex
      SF, in which we performed sternal osteosynthesis and a second group treated only
      conservatively. We studied the correlation between anatomo-lesional status and
      the diagnostic, therapeutic and prognostic factors. The study concluded that SF
      was a benign entity that can be safely managed with analgesia and rest. Selected
      cases can benefit from sternal osteosynthesis.

PMID- 18320795
TI  - [Pre-test probability of obstructive sleep apnea].
AB  - The obstructive sleep apnea syndrome (OSAS) is a condition characterized by
      repeated breathing pauses during sleep and associated with sleep fragmentation,
      intermittent hypoxia and increased, cardiovascular risk. The diagnosis of OSAS
      requires polysomnography, an expensive and time consuming technique, which still
      represents the gold-standard method. Several predictive mathematical models have
      been developed for the prediction of OSAS. These models combine subjective
      parameters (such as sleepiness, witnessed apneas and snoring), morphometric data
      (body mass index, neck circumference and cephalometric measures), associated co
      morbidities (such as hypertension), and oximetry data.

PMID- 18320796
TI  - [Physiopathology of cystic fibrosis and of infections associated to this
      disease].
AB  - Cystic fibrosis (CF) is one of the most common lethal inherited diseases in the
      caucasian population. The hope of understanding the physiopathology of CF
      appeared after identification of the gene which encodes CF. The alteration in
      CFTR protein breaks the hydric balance of the mucosal secretions, producing mucus
      with increased viscosity. Broncho-pulmonary infections are constant encountered
      because of the stasis of the mucus. The most common bacterial pathogens in the
      sputum of patients with MV are Haemophilus influenzae, Staphylococcus aureus,
      Pseudomonas aeruginosa, Burkholderia cepacia. MV remains a severe, incurable
      disease, but the evolution is getting better because of the improvements of care
      methods.

PMID- 18320797
TI  - [Thoracoscopic sympathectomy for arterial ischemia of the upper extremities: a
      case report].
AB  - INTRODUCTION: Thoracoscopic surgery reduce the morbidity of sympathectomy. Major
      indications of video-assisted sympathectomy (VAT) include hyperhidrosis,
      Raynaud's disease, causalgia, and reflex sympathetic dystrophy. Because little
      information is available in the national and international literature VAT
      sympathectomy in the treatment of upper extremities ischemia, we decided to
      present our first case. CLINIC CASE: The 38 years old patient was hospitalized
      for left upper-extremity ischemia (Raynaud's syndrome). Thoracoscopic
      sympathectomy was performed with resection of the main trunk proximally
      immediately after the stellate ganglion and distally at the level of T4 and
      identification and resection of 2 collateral branches of the sympathetic chain T2
      T3. RESULTS: The postoperative evolution demonstrated evident clinical benefit.
      The thermography performed postoperative showed hyperthermia and hyper
      vascularization in the left hemithorax with a difference of temperature of 2
      degrees C between the two sides of the thorax. COMMENT: Before the advent of VAT,
      thoracic sympathectomy was performed only in highly selected patients because of
      its invasiveness. Now VAT sympathectomy is considered in most cases as the last
      resort to prevent extensive and successive amputation. Because the procedure is
      minimally invasive, safe, and associated with a low rate of complications, it
      should be considered earlier in the natural course of this disease.

PMID- 18320798
TI  - [TNF-alpha blockers, rheumatoid arthritis and pulmonary tuberculosis].

PMID- 18320799
TI  - [Smoking reduction--an alternative solution?].

PMID- 18320800
TI  - [Pneumology. Memories of a beginning].

PMID- 18320801
TI  - [When will young surgeons start their researches in the medical school?].

PMID- 18320803
TI  - [Current status of initial staging and posttreatment response evaluation in
      esophageal carcinoma].
AB  - There has been remarkable progress in diagnostic modalities in recent years. The
      development of endoscopic instruments and introduction of fluoro deoxy glucose
      positron emission tomography (FDG-PET) and sentinel node (SN) diagnosis markedly
      improved diagnostic quality. The requirement for individualized treatment is
      increasing with the progress in less-invasive treatment, and therefore it is
      necessary to select the optimal treatment individually on the basis of accurate
      tumor staging. In diagnosis of the T category, zoom endoscopy and
      autofluorescence imaging/narrow band imaging technology improved the diagnostic
      accuracy of T1 stage. T2 or higher tumors are diagnosed with endoscopic
      ultrasonography (EUS) and multidetector computed tomography (CT). In diagnosis of
      the N category, FDG-PET was expected to be useful. However, it often gave false
      negative lymph node (LN) results, and was revealed to have low sensitivity in
      contrast to high specificity. It is important to detect swollen LNs using CT and
      then to assess qualitatively the presence or absence of metastasis with EUS and
      FDG-PET. SN diagnosis using radioisotopes as tracers was introduced as
      preliminary research for subsequent less-invasive surgery. In diagnosis of the M
      category, FDG-PET is currently the most important to obtain additional
      information missed on CT, because FDG-PET can assess the whole body. For response
      evaluation to neoadjuvant treatment, FDG-PET is extremely useful. It can predict
      histologic response and postoperative survival accurately and allow diagnosis of
      distant metastases in the entire body simultaneously. All information needed for
      a decision on surgical indications can be acquired noninvasively, and therefore
      FDG-PET may be the key modality in multimodality treatment.

PMID- 18320804
TI  - [Recent advances of endoscopic treatment for esophageal cancer].
AB  - The indications for endoscopic treatment are limited to cases without lymph node
      metastasis, because it is only a local therapy. The relationship between cancer
      depth and lymph node metastasis has been clarified based on the pathologic
      analysis of lymph nodes removed during esophagectomy for early esophageal cancer.
      Cancer confined to the lamina propria mucosa rarely undergoes lymph node
      metastasis and complete endoscopic resection (ER) is indicated. ER allows the
      esophagus to be preserved and is less invasive, enabling specimens to be
      pathologically examined. Lesions extending over large area can be resected by
      repeating endoscopic mucosal resection (EMR), but have recently been resected
      using endoscopic submucosal dissection (ESD), as indicated for gastric cancer.
      Which of the two procedures, EMR or ESD, to be chosen depends on the difficulty,
      skill of the surgeon, time to be spared, and economic management. ER is now
      performed in SM1 without lymph node metastasis, although some patients require
      additional treatment after pathologic examination of resected lesions.

PMID- 18320805
TI  - [Chemoradiotherapy].
AB  - In Western countries, chemotherapy or chemoradiotherapy followed by surgery is
      the standard treatment and definitive chemoradiotherapy is also standard
      treatment option for localized advanced esophageal cancer. On the other hand, in
      Japan, only surgery is recognized as standard of care. The position of definitive
      chemoradiotherapy is unclear in Japan because the evaluation of chemoradiotherapy
      has not done well so far. Prospective single arm phase II trial of definitive
      chemoradiotherapy (JCOG 9906) whose primary endpoint is survival was carried out
      in Japan recently. The survival outcome in JCOG 9906 compared favorably with
      those of surgery in ordinary institutions. However, the survival in JCOG 9906 was
      worse than those of surgery in high volume center or cancer center. Late
      radiation morbidity and the management of non-CR or recurrences after CR cases
      are major issues in JCOG 9906. In future, new strategy of improved radiotherapy
      such as 3-D planning, avoiding risk organs and heavy ion therapy or proton
      therapy, improved medical treatment such as using new anticancer agents or
      molecular targeting drugs, and the establishment of feasibility in salvage
      surgery will be required for advances of survival for esophageal cancer.

PMID- 18320806
TI  - [Standard radical esophagectomy in thoracic esophageal cancer].
AB  - In Japan, the standard radical surgical procedure in patients with thoracic
      esophageal cancer is right thoracoabdominal esophagectomy with lymphadenectomy.
      However, with the development of endoscopic surgery and improvements in
      chemotherapy and chemoradiotherapy, the role of radical surgery has been
      changing. The indications for radical surgery are stage I disease without
      indications for endoscopic resection (endoscopic mucosal resection or endoscopic
      submucosal dissection), stage II disease, or stage III disease without T 4
      tumors. Because of the favorable results of chemoradiotherapy in the treatment of
      stage I disease, the Japan Clinical Oncology Group (JCOG) started a randomized,
      controlled trial comparing surgery and chemoradiotherapy in the treatment of
      stage I thoracic esophageal cancer. The 5-year overall survival rates in patients
      who underwent surgery alone for thoracic esophageal cancer were 88% with stage I
      and 52% with stage II + III disease in Japan. The most important area in
      lymphadenectomy is the region from the neck to superior mediastinum, and three
      field dissection is widely performed in Japan. However, there is no evidence that
      three-field dissection is necessary or that two-field dissection is sufficient.
      The efficacy of postoperative adjuvant chemotherapy for the treatment of thoracic
      esophageal cancer was confirmed in a Japanese randomized, controlled trial and it
      is expected that the timing of adjuvant chemotherapy will change from post- to
      pre-surgery (neoadjuvant chemotherapy).

PMID- 18320807
TI  - [Thoracoscopic radical esophagectomy for esophageal cancer].
AB  - Thoracoscopic esophagectomy for cancer has become common in the 10 years after
      the introduction of the procedure, with advances in instrumentation and
      techniques. Thoracoscopic surgery is associated with the advantage of preserving
      pulmonary function and reducing pulmonary complications by reducing chest wall
      injury and blood loss. Although it cannot be evaluated subjectively,
      understanding the microanatomy under a magnified view, education through viewing
      on a monitor, and the ability to reproduce the whole procedure are advantages.
      However, to perform lymph node dissection as efficiently as in open surgery,
      substantial learning of the procedure is necessary. To steepen the learning
      curve, sharing and disclosing knowledge and information are essential, as well as
      direct instruction and hands-on seminars given by skilled experts.

PMID- 18320808
TI  - [Salvage surgery after definitive chemoradiation for esophageal carcinoma].
AB  - Definitive chemoradiation has become an effective modality for the treatment of
      advanced esophageal carcinoma, although local residual lesions or recurrence are
      detected in more than 50% of patients. For those patients, resection is the only
      salvage therapy. More than 40% of patients who undergo complete resection
      survive. After chemoradiation for esophageal carcinoma, severe adhesions may
      develop between the primary lesion and surrounding vital organs, leading to
      difficulty in R0 resection. Systemic function including the lungs, heart, and
      bone marrow could be also severely impaired. This may result in many severe
      complications after salvage surgery, such as airway necrosis or mediastinitis. To
      reduce complications, we restrict lymph node dissection, conserve the right
      bronchial artery, and reconstruct with a gastric tube through the poststernal
      course. It is also important to modify the method in each case. The more patients
      select chemoradiation for curative therapy of esophageal carcinoma, the more
      salvage surgery is needed. Surgeons should consider the indications and
      techniques for esophageal surgery to increase cure rates and decrease morbidity.

PMID- 18320810
TI  - [Meaning of fundamental law for anti-cancer measures and problem of cancer
      medical treatment].

PMID- 18320811
TI  - [Envisioning quality measurement systems of cancer care].

PMID- 18320812
TI  - [Preservation and transplantation of parathyroid glands during total
      thyroidectomy].

PMID- 18320813
TI  - [Stop the "surgeon shortage": what could be done and what should be done right
      now. Series 2: Improvement of working environment].

PMID- 18320815
TI  - [Complete genome sequence analysis of a newly isolated paramyxovirus Tianjin
      strain].
AB  - Paramyxovirus Tianjin strain is the high-pathogenic virus to primate and might
      also cause human lower respiratory tract infection. To determine the genome
      structure, variation features and phylogenetic position, the complete nucleotide
      sequence of paramyxovirus Tianjin strain was analyzed. The homology comparison
      and phylogenetic analysis of the nucleotide and the deduced amino acid sequences
      among paramyxovirus Tianjin strain and the 28 strains in seven genera and the 7
      unclassified viruses of Paramyxoviridae were performed. The results suggested
      that Tianjin strain is a member of the Respirovirus genus in the Paramyxovirinae,
      Paramyxoviridae and has the closest relationship to Sendai virus. Its genome
      length and composition are similar to the previously published Sendai virus
      except one extra glutamic acid residue increasing at the C terminus of Large
      protein due to the genomic RNA mutation at position A15240C. 440 unique
      nucleotide variations of Tianjin strain lead to 110 amino acid residue changes,
      making it differed from any other Sendai viruses. The phylogenetic analysis
      reveals paramyxovirus Tianjin strain doesn't belong to any of the three known
      evolution lineages of Sendai viruses and locates at a separate evolution branch.
      The obvious distinctions of genome nucleotide sequence, host tropism and
      pathogenicity suggest that paramyxovirus Tianjin strain might represent a novel
      genotype of Sendai virus.

PMID- 18320816
TI  - [Genetic characterization of Chinese rubella virus isolates from 2003 to 2007].
AB  - 57 rubella virus strains were isolated using Vero cell line or Vero/SLAM cell
      line from patients' throat swabs during rubella outbreaks and sporadics in 10
      provinces of China from 2003 to 2007. Fragments of 1107 nucleotides of E1 genes
      of the isolates were amplified by RT-PCR, the PCR products were directly
      sequenced and analyzed. The phylogenetic analysis based on 739 nucleotides showed
      that out of 57 Chinese rubella virus strains, 55 belong to a distinguish branch
      of 1E genotype when comparing with 1E genotype rubella strains from other
      countries, and the other 2 Chinese rubella virus strains belong to 2B genotype.
      Most of the nucleotide mutations of 57 rubella viruses were silent mutations, and
      the amino acid sequences were highly conserved. Except one amino acid change
      (Thr212 --> Ser212) in two rubella viruses at the hemagglutination inhibition and
      neutralization epitopes, there had no change found at the important antigenic
      epitope sites of the other rubella viruses. 1E genotype rubella viruses isolated
      from 10 provinces of China from 2003 to 2007, and two imported 2B genotype
      rubella viruses from Vietnam suggested that 1E genotype was the predominant
      genotype in this period of time. The rubella virus genotypes circulated during
      2003 to 2007 were different from that circulating during 1979 to 1984 and 1999 to
      2002, the rubella prevailed in recent years was mainly caused by 1E genotype
      rubella viruses with multi-transmission routes.

PMID- 18320817
TI  - [Effect of GBV-C/HIV coinfection on HIV/AIDS disease progression and HIV
      replication].
AB  - Several research groups have recently reported that persistent GB virus C (GBV-C)
      co-infected with human immunodeficiency virus (HIV) leads to slower AIDSs disease
      progression than HIV-1 infection alone. However, these findings were not
      confirmed by several other studies. To investigate the association between GBV-C
      replication and plasma HIV loads and CD4+ T cell counts, 203 HIV-1 positive
      former blood/plasma donors(FBDs) were enrolled from Fuyang city of Anhui Province
      in China. Plasma specimens were collected from them and were tested for GBV-C
      using RT-PCR and ELISA. Out of 203 specimens, 52 (25.6%) cases were positive for
      GBV-C, including 35 male (67.3%) and 17 female (32.7%) cases. No significant
      association was identified between GBV-C infection and CD4+ T-cell counts or
      between GBV-C infection and HIV viral loads. Since all the subjects studied were
      naive to ART, the influence of therapy on AIDS disease progression was ruled out
      in this study. Overall, our data indicated that HIV-1 positive male FBDs were
      prone to be infected, GBV-C coinfection with HIV-1 does not significantly
      influence HIV/AIDS disease progression during the late stage of chronic HIV-1
      infection.

PMID- 18320818
TI  - [Genetic variation in VP7 gene of rotavirus serotype G3 predominated in
      Changchun, China].
AB  - Group A rotavirus (RV) is the most important etiologic agent of severe
      gastroenteritis among children and the development of an effective vaccine
      becomes the top public health priority. Since survey of RV serotypes circulating
      in local community is important for introduction or development of RV vaccine, RV
      serotype G3 had proved as the predominant strain in Changchun from 2001 to 2005.
      Stool specimens collected from children with acute diarrhea were tested for group
      A rotavirus by enzyme-linked immunosorbent assay (ELISA) and RV isolates were
      typed by reverse transcription-polymerase chain reaction (RT-PCR) using serotype
      specific primers. The complete VP7 gene segments of 31 rotavirus strains selected
      in Changchun from 1999 to 2005 were amplified with RT-PCR. Amplicons were cloned
      and sequenced. Comparative analysis of the VP7 sequences showed that there were
      no obvious differences among 31 RV strains. There was similar genetic variation
      among VP7 genes during the same RV season. The nucleotide sequence of VP7 gene of
      six G3 RV strains had one base deletion at nt1038 in 2003 RV season. The
      nucleotide mutations in regions A, B and C of VP7 gene took place at the same
      position or position near-by. Increase of nucleotide mutation in non- high
      variation region may benefit maintenance of serotype G3 as pre dominant strain
      after 2002. Increase of non continuous variation in non-high variation regions
      was notable.

PMID- 18320819
TI  - [Laboratory diagnosis and molecular characterization analysis of the H5N1
      influenza virus isolated from the first human case in Shenzhen, China].
AB  - The tracheal aspirates and serum samples of a suspected human case of high
      pathogenic avian influenza (firstly found in Shenzhen, China) were collected and
      tested by a series of assays. The results showed that the RNA extracted from the
      tracheal aspirate specimens of the patient was confirmed positive for H5N1 avian
      influenza virus by Real-time PCR. The H5N1 avian influenza virus was isolated
      from patient's tracheal aspirates on MDCK cell and was named
      A/Guangdong/2/06(H5N1). The viral load of tracheal aspirates collected at
      different time points were detected by Real-time PCR. The virus
      microneutralization and the antigenic ratio of human H5N1 isolated were also
      assayed. It was found that when the virus load decreased gradually after the
      disease onset, the serum neutralizing antibody titer in the patient increased to
      1 : 160 and subsequently decreased gradually. By molecular analysis, the eight
      gene segments of A/Guangdong/2/06 revealed to be similar to that of H5N1 avian
      influenza viruses isolated from south China in 2005-2006. However, there were
      obvious differences in the gene sequence of the detected H5N1 viral RNA as
      compared with that of the strains isolated from Vietnam, Thailand and Indonesia.

PMID- 18320820
TI  - [Analysis of the amino acid changes of the hemagglutinin of H5 avian influenza
      virus].
AB  - We introduced 38 single-point amino acid changes into the hemagglutinin (HA)
      protein of the reassortmented A/Duck/Mongolia/54/01 (H5N2) strain by a PCR random
      mutation method. The percentage of amino acid changes on the HA domain that did
      not abrogate hemadsorption activity was calculated to be 89%. Changes in the
      amino acids of the HA2 domain were observed to be about half of those in the HA1
      domain of these mutants. We assumed that amino acid changes in the HA1 domain
      afforded more flexibility in maintaining the functions of the HA protein than did
      those in the HA2 domain. Changes at two positions allowed the mutants to have
      same characteristics with respect to HA function despite the difference in the
      substituted amino acid. The results suggested that the effect on hemadsorption
      activity of an amino acid change on the HA protein primarily depends on the
      position rather than the species of substituted amino acid. An amino acid change
      at residue 122 from Trp to Arg and 179 from His to Arg resulted in the loss of
      hemadsorption activity of the HA protein. Site 122 is near the antibody binding
      site A, and site 179 is in the receptor binding domain (RBD) of HSHA. So that we
      suggest residue position 179 or 122 is very important to maintain the structure
      of RBD or antigenic site of H5HA. Position 4 in HA1 changed from Cys to Arg and
      position 148 in HA2 changed from Cys to Tyr also resulted in the loss of
      hemadsorption activity of the HA protein. Cys plays an important role in
      maintaining the structure of HA protein by means of S-S bonds. 3 potential
      glycosylation sites (Asn-X-Ser/Thr) were lost in our experiment that did not lose
      the hemadsorption activity of HA. Some interesting positions need to be analyzed
      more finely. Some amino acid changes identified in vitro experiment may serve as
      molecular markers for assessing the pandemic potential of H5N1 field isolates.

PMID- 18320821
TI  - [Construction and immunogenicity of attenuated Salmonella typhimurium stably
      harbouring DNA vaccine against Newcastle disease virus].
AB  - The fusion protein (F) gene of Newcastle disease virus was amplified by
      polymerase chain reaction (PCR) from the recombinant plasmid pVAX1-F, and
      subcloned into eukaryotic expression vector pmcDNA3. 1+. The F gene was
      identified by sequencing. The recombinant plasmid was transformed into attenuated
      Salmonella typhimurium SL7207, and the recombinant was designated as SL7207
      (pmcDNA3. 1-F). In vitro and in vivo experiments showed that the plasmid
      stability of pmcDNA3. 1-F was apparently higher than that of pcDNA3. 1-F in
      SL7207. In order to compare the immune response induced by these two re combinant
      bacteria, BALB/c mice were immunized orally with them at the dosage of 2 x 10(9)
      CFU respectively. Both SL7207(pcDNA3. 1-F) and SL7207(pmcDNA3. 1-F) initiated F
      specific serum and mucosal antibodies in immunized mice. Furthermore, 4-day-old
      SPF chickens were immunized with SL7207(pcDNA3. 1-F) and SL7207(pmcDNA3. 1-F) at
      the dosage of 5 x 10(9) CFU and boosted two weeks later with the same dosage.
      Humoral and intestinal mucosal immune responses were observed and their levels
      were significantly higher than that of negative and positive controls. The result
      of protective efficacy showed that the chickens immunized with SL7207(pmcDNA3. 1
      F) had the protective rate of 70.0%, higher than that of the SL7207 (pcDNA3. 1-F)
      with 50.0%. In summary, the DNA vaccine delivered by attenuated Salmonella
      typhimurium has good immunogenicity. A novel mucosal DNA vaccine has been
      developed and could be useful for controlling the infection and epidemic of
      Newcastle disease in the poultry.

PMID- 18320822
TI  - [Study on the DNA immunogenicity of fusion and attachment glycoproteins of Nipah
      virus].
AB  - The two mammalian codon optimized genes, F and G genes of Nipah virus, were
      generated by assembly PCR, and inserted into mammalian expression vector pCAGGS
      under chicken beta-actin promoter to construct pCAGG-NiV-F and pCAGG-NiV-G.
      Syncytium formation was induced in BHK cells by plasmid pCAGG-NiV-F and pCAGG-NiV
      G transfection, which indicate recombination proteins F and G were expressed in
      BHK cell and possessed good biologic activity. Six-week-old female BALB/c mice
      were intramuscularly primed with 100 microg pCAGG-NiV-F, pCAGG-NiV-G or pCAGG-NiV
      F+ pCAGG-NiV-G respectively, and boosted with same dose after 4 weeks. The sera
      were collected at 3 weeks post second boost. The serum IgG against Nipah virus F
      and G proteins was detected by indirect ELISA using recombinant Baculovirus
      expressed Nipah F and G glycoproteins. The results showed that specific
      antibodies possessed good sensitivity and specificity. Furthermore, the G and F
      proteins' specific antibodies could neutralize the infectivity of VSVdeltaG* F/G
      (the NiV F and G envelope glycoproteins psudotyped recombinant vesicular
      stomatitis virus expressing green fluorescence protein). And, pCAGG-NiV-G also
      induced higher titer of neutralizing antibody response than pCAGG-NiV-F did. The
      result indicates that DAN immunization is an efficient vaccine strategy against
      Nipah virus.

PMID- 18320823
TI  - [Sequence analysis for the complete provial genome of endogenous avian leukosis
      virus strain SD0501].
AB  - The genomic DNA extracted from chicken embryo fibroblasts (CEF) of SPF chickens
      from three chicken farms was used as template to amplify the ALV proviral DNA by
      PCR with four pairs of primers, high positive detection rates of gag - gene
      (29/46), pol - gene (27/46), env - gene (24/46) and LTR fragment (31/46) were
      achieved. Eight continuous and overlapping fragments were amplified from one DNA
      sample with 8 pairs of primers according to published sequences, then cloned into
      the TA vector and se quenced. The complete sequence of the whole genome of ALV
      strain SD0501 was established and analyzed with DNAstar software. Comparisons of
      SD0501 sequence with that of other representative endogenous avian virus strains
      demonstrated that the genomes of ALV were relatively conservative, the nucleotide
      identity of all the strains was over 99.1%, and env - gene was over 98.5%.
      However, a low identity was demonstrated among the representative strains of
      different subgroups, especially, the env - gene showed obvious difference, the
      corresponding identity was as low as 56.3% - 91.5%.

PMID- 18320824
TI  - [Construction of recombinant fowlpox virus expressing E0 gene of classical swine
      fever virus shimen strain and the animal immunity experiment].
AB  - The CSFV E0 gene was amplified from the plasmid pMD18-T-E0 by PCR and cloned into
      the FPV-P11 and FPV-pSY. The identified recombinant DNA was transfected into
      chicken embryo fibroblasts (CEF) to package Fowlpox virus. E0 gene was confirmed
      to be integrated into the genome of recombinant Fowlpox virus by PCR, and Western
      blot was employed for detection of E0 expression in the chicken embryo
      fibroblasts infected with recombinant Fowlpox virus . The results of ELISA showed
      that systemic immune response to CSFV could be induced effectively after the mice
      were immunized three times with recombinant Fowlpox virus through celiac route,
      the titer of antibody was 1 : 4096. The protection experiment showed that 75% of
      piglets immunized three times with recombinant Fowlpox virus were survived,
      indicating that the recombinant Fowlpox virus was effective. This paper lays
      foundation for the study of CSFV live vector vaccine.

PMID- 18320825
TI  - [Molecular characterization of cotton leaf Curl Multan virus and its satellite
      DNA that infects Hibiscus rosa-sinensis].
AB  - Virus isolate G6 was obtained from Hibiscus rosa-sinensis showing yellow and leaf
      curl symptoms in Guangzhou, Guangdong Province. The complete nucleotide sequence
      of DNA-A was determined to be 2 737 nucleotides encoding six potential ORFs.
      Comparison showed that G6 DNA-A had more than 89% sequence identify with all
      isolates of Cotton leaf curl Multan virus (CLCuMV) and shared the highest
      sequence identify (96.1%) with CLCuMV isolate 62. G6 DNA-A had 87.1%-89.8%
      sequence identity with those of CLCuRV isolates, while less than 87% identities
      with other begomoviruses. Phylogenetic analysis of G6 DNA-A and selected
      begomoviruses showed that G6 was most closely related to CLCuMV isolates, and
      they clustered together as a separate branch. Satellite DNA molecule (G6 DNAbeta)
      was found to be associated with G6 using the primers beta01 and beta02. G6
      DNAbeta contains 1346 nucleotides, with a potential functional ORF (C1) in
      complementary sense DNA. Pairwise comparison indicated that G6 DNAbeta had the
      highest sequence identities with CLCuMV DNAbeta (92.1%) and CLCuRV DNAbeta
      (88.7%), but less than 80% sequence identities with other reported satellite DNA
      molecules. Phylogenetic analysis indicated that G6 DNAbeta was most closely
      related to CLCuMV DNAbeta and the two DNAbetas clustered together as a separate
      branch, and formed the main branch with DNAbeta of CLCuRV and MYVV-Y47. It is
      concluded that G6 infecting Hibiscus rosa-sinensis is an isolate of CLCuMV.

PMID- 18320826
TI  - [Discovery and identification of WU polyomavirus in children from Zhejing
      region].
AB  - WU polyomavirus, which was firstly discovered in 2007, is a new human
      polyomavirus belonging to Polyomaviridae and containing circular double-stranded
      genomic DNA. In this study, the 278 clinical sputum specimens from children under
      5 years old were collected from Wenzhou Medical College affiliated Wenling First
      Hospital, Zhejiang Province. Based on identification assay of WU polyomavirus
      previously reported, a WU polyomavirus was identified from clinical samples
      successfully, the positive rate was 0.4%. The sequences of PCR products were
      identical to that of VP2 gene and large T antigen gene derived from WU
      polyomavirus reported. The above results strongly suggested that the WU
      polyomavirus isolated was firstly found in Chinese children with acute lower
      respiratory tract infections. This study provides a firm basis for further
      research of WU polyomavirus.

PMID- 18320827
TI  - [Replication of duck plague virus in artificially infected ducks detected by in
      situ hybridization].
AB  - Replication of duck plague virus(DPV) in artificially infected ducks were
      detected by in situ hybridization (ISH) which employed a 37bp oligonucleotide as
      probe designed according to DPV DNA sequence in GenBank. The results indicated
      that DPV DNA was detected in liver, intestine and bursa Fabricius at 4 h, in
      spleen and esophagus at 6h, in thymus at 12h post infection; DPV DNA in lung and
      kidney was detected only in dead ducks and no positive signal was detected in
      muscle, heart, cerebrum and pancreas. DPV DNA was distributed in cell nucleus and
      cytoplasm. Hepatocytes, sinus endodermal cells and Kuffer's cells were the mainly
      infected cell types in liver. DPV DNA was mainly detected in epithelium of villi,
      in lamina propria of intestinal villi of duodenum, in stratum spinosum of
      esophagus, and in epithelium, cortex, medulla of bursa Fabricius. The positive
      signals were mainly detected in medulla of thymus, lymphocytes and macrophages of
      spleen. The research suggests that ISH is a direct and specific method in
      detecting DPV DNA in paraffin sections and it's also a good method for virus
      diagnosis and DNA location of DPV.

PMID- 18320828
TI  - [The inactivating effect of chito-oligosaccharides on TMV particles in vitro].
AB  - To confirm the inactivating effect of chito-oligosaccharides on Tobacco mosaic
      virus (TMV) par ticles in vitro, the difference of TMV pathogenicity was
      evaluated according to the decrease of local lesion numbers after inoculating
      with TMV mixed with chito-oligosaccharides (DP3-10) in Nicotiana glutinosa, and
      the virion structural change was studied by transmission electron microscopy
      after mixed with chito-oligosaccharides. In the range of tested concentrations of
      chito-oligosaccharides (100-1000 microg /mL), the numbers of local lesions were
      strongly reduced with over 30% decrement, and the 88.4% reduction gained at the
      concentration of 600g /mL. It revealed that treatment with chito-oligosaccharide
      solution of 300-500 microg /mL directly broke TMV particles into tiny pieces of
      50-150nm long, and that treatment with solutions of 600-1000 microg/mL caused
      virus particle agglomerated. The data presented here suggested that chito
      oligosaccharides exerted strong inactivating effect on plant virus in vitro.

PMID- 18320829
TI  - [Research advances on the role of human papillomavirus structural proteins in
      viral infection].

PMID- 18320830
TI  - Presentation and aims of the round table.

PMID- 18320831
TI  - Recovery of swallowing function following surgery for advanced buccopharyngeal
      carcinoma.
AB  - More than 20 years have passed since the introduction of surgical techniques
      based on distal myocutaneous flaps or microvascular flaps in the reconstruction
      after head and neck cancer resections. The experience gained from the beginning
      of these techniques until today, has improved the possibility to better predict
      functional impairment of swallowing in patients and its possible recovery. This
      contributes to a better counselling of the patient and better prediction
      concerning his/her quality of life. Despite the time passed and good progress in
      the development of microsurgical techniques, the literature shows that many
      differences still remain among Authors concerning choice of flap and its inset in
      relation to the anatomical sites and the extent of resection. Many other
      variables may condition post-operative swallowing (pre- or post-operative
      radiotherapy, general conditions of the patient ...) thus contributing to a more
      difficult comparison of the different series reported in the literature. Personal
      experience is based upon surgical treatment in >60 patients with advanced bucco
      pharyngeal cancer, all of whom evaluated post-operatively by video-endoscopy and
      video-fluoroscopy. In summary, data collected both from personal experience and
      the literature show that difficulties still remain in correct evaluation of
      swallowing in these patients. This is mainly due not only to lack of a commonly
      accepted scheme of classification to quantify the anatomical defect but also to
      differences between Authors concerning choice of the type of flap and the mode of
      inset.

PMID- 18320832
TI  - Endoscopic evaluation of neurological dysphagic patients.
AB  - Dysphagia is a frequent finding in neurological patients and is a symptom related
      to the severity of the clinical picture. The swallowing impairments, in these
      patients, increase the risk of aspiration pneumonia, that leads to death, in at
      least 6% of patients, within the first year. Therefore, evaluation of the
      swallowing status is essential in patients with dysphagia and videofluoroscopic
      study of swallowing (VFSS) is the method of choice. It cannot be performed in all
      patients on account of the complexity of the procedure and since they must be
      brought to the Radiology Unit. In the 1980, a new bedside method was introduced,
      namely: fiber-optic endoscopic study of swallow (FESS) which is easy, low-cost,
      well-tolerated and repeatable. We use this bedside technique to assess swallowing
      function in patients with dysphagia admitted to acute care units, neurological
      and internal medicine units. The evaluation aims to indicate the safer
      nutritional method (oral intake, feeding tube or percutaneous gastrostomy) and,
      consequently, reducing the risk of aspiration pneumonia during hospitalization.
      We found that more than 50% of the dysphagic patients present cerebrovascular
      injuries and in 2% of the population, the first diagnostic hypothesis of
      Myasthenia Gravis can be made with the FESS technique. In 60%, we indicate a
      change in nutritional method: in 20% we indicate percutaneous endoscopic
      gastrostomy (PEG). With these indications, none of those patients had aspiration
      pneumonia. Our protocol for the bedside fiberoptic study of neurological patients
      with dysphagia has demonstrated its efectiveness by eliminating the incidence of
      aspiration pneumonia.

PMID- 18320833
TI  - Rehabilitation protocol of dysphagia after subtotal reconstructive laryngectomy.
AB  - Dysphagia is a constant complication of subtotal reconstructive laryngectomy, due
      to modifications in the anatomy and in sensitivity of the larynx and pharynx. The
      reduced sphincteric activity of the larynx can enhance aspiration with a higher
      risk of pneumonia. In our opinion, the presence of the tracheotomy tube in the
      first weeks after surgery interferes with proper mobility of the laryngo-tracheal
      axis during swallowing, as it anchors the trachea to the skin. We have conducted
      swallowing rehabilitation, without the tracheotomy tube, ready to aspirate
      eventual saliva or food debris dropping into the trachea. This protocol has been
      applied in 33 patients undergoing subtotal reconstructive laryngectomy and better
      patient compliance and swallowing performance were observed. The period to
      recover complete autonomous oral intake is less than one month and none of these
      patients showed signs or symptoms of aspiration pneumonia during hospitalisation
      or follow-up. This rehabilitation protocol is, therefore, a valid and effective
      alternative to other well-known procedures.

PMID- 18320834
TI  - Trans-tracheostomic endoscopy of the larynx in the evaluation of dysphagia.
AB  - Laryngeal endoscopy plays a determinant role in clinical evaluation of dysphagia.
      The examination is performed by means of a trans-nasal approach with a flexible
      fiberoptic endoscope, able to visualize the pre- and post-deglutitory steps of
      the pharyngeal phase of swallowing. In patients with tracheostomy, it is possible
      to visualize the glottic or neoglottic function during the intra-deglutitory
      phase, performing the examination through a trans-tracheostomic route. The
      procedure and indications of this endoscopic technique are described.

PMID- 18320835
TI  - Surgical rehabilitation of dysphagia after partial laryngectomy.
AB  - Surgical rehabilitation of dysphagia in patients who have undergone partial
      laryngectomy is aimed at improving the sphincteric action of the larynx, the
      anatomy and physiology of which are impaired. The interventions indicated for
      this purpose can be performed either with an external or endoscopic approach. The
      Authors present early results of their experience employing injection
      laryngoplasty with autologous fat, bovine collagen (Zyplast, McGhan Medical
      Corporation, Fremont, CA, USA) and PDMS (Vox Implants, Uroplasty Inc, Minnetonka,
      MN, USA), performed by means of fiberendoscopy, under local anaesthesia, and
      microlaryngoscopy, under general anaesthesia.

PMID- 18320836
TI  - Clinical non-instrumental evaluation of dysphagia.
AB  - Clinical non-instrumental evaluation plays an important role in the assessment of
      the dysphagic patient. This evaluation, called "bedside examination", aims to
      establish whether dysphagia is present, evaluating severity, determining the
      alterations which cause it, planning rehabilitation, testing outcome of
      treatment. The assessment takes into consideration anamnesis regarding the
      swallowing problem, evaluation of the anatomy and functionality, of sensitivity
      and the reflexes, of the swallowing apparatus. Finally, the oral feeding test is
      performed, which evaluates the oral and pharyngeal phases of swallowing. The
      examination performed in the neurologic patient is different from that performed
      in the patient submitted to ENT or maxillo-facial surgery.

PMID- 18320837
TI  - Role of videofluoroscopy in evaluation of neurologic dysphagia.
AB  - For many years, videofluoroscopy was considered the gold standard for studies on
      swallowing disorders, and only recently has its role been challenged, due
      primarily to the widespread use of videoendoscopy in the evaluation of dysphagia.
      Albeit, videofluoroscopy still maintains its key role in this area and, in
      particular, in studies on dysphagia of neurological origin, on account not only
      of the possibility, with this procedure, to achieve complete and dynamic
      evaluation of all phases of deglutition, but also the high sensitivity and
      specificity in revealing the presence of inhalation. Aim of the present
      investigation was to analyse the technical procedure of videofluoroscopy and the
      principal indications in the study of dysphagia of neurological origin, in the
      attempt to reveal the advantages and disadvantages occurring in this examination,
      also with respect to other methods adopted in the evaluation of dyphagia. In
      conclusion, at present, no instrumental examination can be defined as ideal for
      the study of swallowing, but it can be seen that, with each of these procedures,
      the information forthcoming is actually complementary, thus achieving the aim to
      proceed as correctly and rapidly as possible, with the management of patients
      with dysphagia.

PMID- 18320838
TI  - Future perspectives in deglutology.

PMID- 18320839
TI  - Bouchut, O'Dwyer and laryngeal intubation in patients with croup.

PMID- 18320840
TI  - Role of cyclooxygenase-2 in tumor progression and immune regulation in lung
      cancer.
AB  - Lung cancer is the leading cause of cancer death all over the world. The low 5
      year survival rate (under 15%) has changed minimally in the last 25 years.
      Amongst different types of lung cancers, non-small cell lung carcinoma (NSCLC)
      types account 25-40%. To improve the survival of lung cancer patients, new
      therapeutic strategies are needed. The search for improved therapies has led to
      the investigation of agents that target novel pathways involved in tumor
      proliferation, invasion, survival and immune regulation. Cyclooxygenase-2 (COX-2)
      is one of the novel targets under evaluation for NSCLC therapy and
      chemoprevention. Although multiple genetic alterations are necessary for lung
      cancer invasion and metastasis, COX-2 may act as central element in orchestring
      these processes. COX-2 plays an important role in all aspects of tumor
      development and growth. It also plays a pivotal role in regulation of cytokines
      and immune responses in NSCLC patients. In this article, we review the
      experimental and clinical evidences on the possible link between COX and NSCLC.

PMID- 18320841
TI  - Biochemical and immunological characterization of E. coli expressed 42 kDa
      fragment of Plasmodium vivax and P. cynomolgi bastianelli merozoite surface
      protein-1.
AB  - Plasmodium vivax is one of the most widely distributed human malaria parasites
      and due to drug-resistant strains, its incidence and prevalence has increased,
      thus an effective vaccine against the parasites is urgently needed. One of the
      major constraints in developing P. vivax vaccine is the lack of suitable in vivo
      models for testing the protective efficacy of the vaccine. P. vivax and P.
      cynomolgi bastianelli are the two closely related malaria parasites and share a
      similar clinical course of infection in their respective hosts. The merozoite
      surface protein-1 (MSP-1) of these parasites has found to be protective in a wide
      range of host-parasite systems. P. vivax MSP-1 is synthesized as 200 kDa
      polypeptide and processed just prior to merozoite release from the erythrocytes
      into smaller fragments. The C- terminal 42 kDa cleavage product of MSP-1 (MSP
      1(42)) is present on the surface of merozoites and a major candidate for blood
      stage malaria vaccine. In the present study, we have biochemically and
      immunologically characterized the soluble and refolded 42 kDa fragment of MSP-1
      of P. vivax (PvMSP-1(42)) and P. cynomolgi B (PcMSP-1(42)). SDS-PAGE analysis
      showed that both soluble and refolded E. coli expressed P. vivax and P. cynomolgi
      B MSP-1(42) proteins were homogenous in nature. The soluble and refolded MSP
      1(42) antigens of both parasites showed high reactivity with protective monkey
      sera and conformation-specific monoclonal antibodies against P. cynomolgi B and
      P. vivax MSP-1(42) antigens. Immunization of BALB/c mice with these antigens
      resulted in the production of high titres of cross-reactive antibodies primarily
      against the conformational epitopes of MSP-1(42) protein. The immune sera from
      rhesus monkeys. immunized with soluble and refolded MSP-1(42) antigens of both
      parasites also showed high titered cross-reactive antibodies against MSP-1(42)
      conformational epitopes. These results suggested that the soluble and refolded
      forms of E. coli expressed P. vivax MSP-1(42) antigens were highly immunogenic
      and thus a viable candidate for vaccine studies.

PMID- 18320842
TI  - Necessity of nuclear and mitochondrial genome analysis prior to assisted
      reproductive techniques/intracytoplasmic sperm injection.
AB  - Assisted reproductive technique (ART) has revolutionized the management of severe
      male factor infertility and in some countries 5% babies are conceived through
      ART/intra cytoplasmic sperm injection (ICSI). However, the carry-home live birth
      rate after several ART cycles is low (18-25%) and this is financially, physically
      and emotionally crippling for the couples. Genetic factors could lead to pre or
      post-implantation failure and thus explain for low ART success rate. Thus, this
      study was planned to understand, if infertile men harbour genetic abnormalities
      which may be iatrogenically transmitted by ART and adversely affect growth
      potential of embryo. Ninety infertile men underwent semen, cytogenetic, Yq
      microdeletion and mitochondrial mutation analysis. Of these, 14.4% cases
      harboured cytogenetic abnormality, and 8.89% Yq microdeletions. A high frequency
      of mitochondrial mutations was found in 23 men with asthenospermia. It is
      important to understand that through ART genetic abnormalities are transmitted to
      offspring, resulting in impaired growth and development potential of embryo and
      poor take-home live birth rate. Thus, genetic analysis is strongly recommend in
      all men with idiopathic infertility who opt for ART to counsel couples and
      provide them with most adapted therapeutics.

PMID- 18320843
TI  - Identification and characterization of lipids from endosomes purified by
      electromagnetic chromatography.
AB  - Traditional separation techniques do not yield endolysosomes of sufficient purity
      to permit detailed biochemical characterization of this important class of
      intracellular vesicles. Here, we have used a magnetic chromatography technique to
      isolate the endosomes from rat peritoneal macrophages and studied their lipid
      composition. Electromagnetic isolation works by retention of colloidal iron
      containing vesicles on magnetic column. The data suggested that both early and
      late endosomes were rich in cholesterol, whereas sphingomyelin (SM) and specific
      phospholipids like phosphatidylcholine. phosphatidylethanolamine,
      phosphatidylglycerol and phosphatidylserine are enriched in the late
      compartments. Our results also indicated that the purified fractions are enriched
      in raft lipids like SM, but not in cholesterol. The endosomal purification method
      described here yields pure endosomes with little or no contamination from
      mitochondria and hence could be used for further biochemical and marker analysis,
      giving insight into mechanisms of endocytic traffic.

PMID- 18320844
TI  - Molecular vibrations and normal modes in L-prolyl-glycyl-glycine using Wilson GF
      matrix method.
AB  - Collagen is one of the most important proteins containing mostly proline
      hydroxyproline and glycine. In collagen, approximately 33 percent of the amino
      acid residues are glycine and they occur at every third position, whereas
      remaining percentage is constituted by mainly proline or hydroxyproline and some
      part by alanine etc. having no definite positional placement in the chain. Thus,
      a study of conformation of proline and glycine containing dipeptides and
      tripeptides is important for understanding the conformation of collagen as a
      sequence of its constituent amino acids. In the present communication, we have
      studied spectral features of L-proline, L-prolyl-glycine (PG), L-prolyl-alanine
      (PA), L-glycylglycine (GG), Collagen and L-prolyl-glycyl-glycine (PGG). We have
      carried out detailed normal mode analysis of only PGG, because interpretation of
      spectra of other proline and glycine containing peptides can be treated as
      derivatives of this molecule. Urey-Bradley force field, which involves non-bonded
      interactions in the gem and cis configurations is used for calculation of normal
      modes. The "best-fit" set of constants are generated for PGG.

PMID- 18320845
TI  - Biological activity predictions, crystallographic comparison and hydrogen bonding
      analysis of cholane derivatives.
AB  - A total of eighteen molecules of cholane derivatives (I-XVIII) (a series of
      steroids) have been included to predict their pharmacological effects, specific
      mechanisms of action, known toxicities, drug-likeness, etc, by using the
      statistics of multilevel neighbourhoods of atoms (MNA) descriptors for active and
      inactive fragments. The biological activity spectra for substances have been
      correlated on SAR base (structure-activity relationships data and knowledge
      base), which provides the different P(a) (possibility of activity) and P(i)
      (possibility of inactivity). Most of the probable activities have been
      characterized by P(a) and P(i) values, which depict that all the molecules have
      high value of teratogen activity. The Lipinski's thumb rule predicts that all the
      cholane derivatives have stronger preponderance for "cancer-like-drug" molecules
      and some of their related analogous have entered in the ANCI (American National
      Cancer Institute) database. Some selected bond distances and bond angles of
      interest have been taken into account and deviation of bond distances/bond
      angles, vis-a-vis the substitutional group and X-H...A intra/intermolecular
      hydrogen bonds has been discussed in detail. X-H...A intra and intermolecular
      hydrogen bonds in the molecules have been described with the standard distance
      and angle cut-off criteria. D-theta and d-theta. scatter plots for intra- and
      intermolecular interactions are presented for better understanding of packing
      interactions existing among these derivatives. There exists only one C-H...O
      intramolecular bifurcated hydrogen bond. while high tendency of intermolecular
      bifurcated hydrogen bonds based on a defined O-H...O has been observed, in which
      O atom acts as a prototype donor as well as acceptor. The frequency of occurrence
      of C-H...O hydrogen bonds is predominant (i.e. 85.7%) in intramolecular
      interactions, whereas in intermolecular interactions, frequency of occurrence for
      O-H...O interactions is 62.9%. Solvent-solute/solute-solvent interactions have
      also been investigated to understand more complicated processes that occur for
      biomolecules in aqueous solutions. The number of hydrogen donors in each
      derivative is less than 5, except for molecule XVIII and which has 91.3% of drug
      likeness, instead of observed range of 96.5-99.39%.

PMID- 18320846
TI  - Quantitative structure-activity relationship of some pesticides.
AB  - Herbicides (benzodiazepinediones), insecticides (dioxatricyclododecenes) and
      larvicides (N-oxalyl derivatives of tebufenozide) have been quantitatively
      investigated to explore the relationship between the molecular structure and
      their biological activity using molecular operating environment (MOE) software.
      The study provides good predictive models, cross-validated by leave-out-one
      method (Loo). The positive contribution of the descriptor n-O (count of oxygen
      atom) suggests the additional oxygen atom substitution at R1 position, in
      addition to benzodiazepine moiety is favorable for herbicidal activity, whereas
      the negative contribution of y component of dipole moment (Dip(y)) indicates that
      electronic interactions are also crucial for the activity. The negative
      correlation of V(SA)2 and globularity (Glo) descriptors clearly indicates that
      the volume, shape, and rigidity of tebufenozide derivatives determine their
      larvicidal activity. The biparametric model for insecticides shows that the
      indicator variable l(CH-CH3) and R(PC) (negative partial charge) are detrimental
      for its activity. Most of the active compounds in the series have shown less
      value for these descriptors. The derived QSAR models also provide valuable
      insights to optimize their toxicity, which remains a major concern for
      environment safety.

PMID- 18320847
TI  - Modulatory effect of Gynandropsis gynandra L. on glucose metabolizing enzymes in
      aflatoxin B1-induced hepatocellular carcinoma in rats.
AB  - The modulation of glucose-metabolizing enzymes activities play a vital role in
      the depletion of energy metabolism and leads to inhibition of cancer growth. In
      the present study, the effect of Gynandropsis gynandra L. extract on aflatoxin B1
      (AFB1)-induced hepatocellular carcinoma (HCC) was studied on glucose-metabolizing
      enzymes in rats. A significant increase (p < 0.001) in the activities of the key
      glycolytic enzymes viz., hexokinase and phosphoglucoisomerase, with a significant
      decrease (p < 0.001) in the gluconeogenic enzymes glucose-6-phosphatase and
      fructose-1,6-bisphosphatase were observed in HCC-bearing rats, when compared with
      the control. Administration of G. gynandra extract caused a significant decrease
      in the activities of glycolytic enzymes and an increase in the gluconeogenic
      enzymes activities to near normal values. Thus, findings suggest the G. gynandra
      extract has a definite modulating role on the key enzymes of glucose metabolism
      in HCC. The modulatory effect may be due to the phytoactive constituents present
      in the extract of G. gynandra.

PMID- 18320848
TI  - Antiphospholipid antibodies in young myocardial infarction patients.
AB  - Myocardial infarction (MI) is a multi-factorial disease which claims many young
      lives. There are very few Indian studies that have investigated antiphospholipid
      antibodies (APLs) in MI patients. APLs have been implicated in arterial
      thrombosis including premature coronary artery and cerebrovascular thrombosis. In
      the present study, the prevalence of two clinically significant APLs-
      anticardiolipin antibody (ACA) and lupus anticoagulants (LA) in young MI patients
      was studied and compared with age- and sex-matched controls. Fifty healthy blood
      donors and 40 young MI patients (less than 45 yrs) diagnosed according to the
      American Heart Association guidelines were recruited for the study. The criteria
      for diagnosis were presence of atleast two of three classical findings including:
      clinical symptoms, diagnostic ECG, and presence of one or more cardiac biomarkers
      out of raised CK-MB isoform and T-troponin on serial measurement. LA and ACA were
      tested by lupus-sensitive activated partial thromboplastin time (aPTT) and ELISA
      respectively. Elevation of ACA was observed in 9 patients, while 6 were positive
      for LA. ACA of IgG isotype was detected in 8 patients. One patient had LA and
      raised ACA of IgG and IgM isotypes. Antiphospholipid antibodies were found to be
      significantly associated with MI in young patients, when considered together (p <
      0.05) and in coronary thrombosis, mild elevation of ACA may be considered
      significant.

PMID- 18320849
TI  - Back to school.

PMID- 18320850
TI  - Fast, funtional & first-rate.

PMID- 18320851
TI  - Skating to patients.

PMID- 18320852
TI  - MCI on the high seas.

PMID- 18320853
TI  - Helicopter shopping.

PMID- 18320854
TI  - Claim only the truth.

PMID- 18320855
TI  - Cleaning up messes. Is emotional intelligence the answer?

PMID- 18320856
TI  - NIMS and ICS: from compliance to competence.

PMID- 18320857
TI  - Diaster school.

PMID- 18320858
TI  - Tribal preparedness.

PMID- 18320859
TI  - Beyond the basics: crush injuries and compartment syndrome.

PMID- 18320860
TI  - EMS' dirty secret. The dark side of an ancient gift.

PMID- 18320861
TI  - A world of hurt.

PMID- 18320862
TI  - Doctors without borders. A physician-led team of volunteers augments emergency
      response in NY.

PMID- 18320863
TI  - Antithrombotic prophylaxis in multiparous women with preeclampsia or intrauterine
      growth retardation in an antecedent pregnancy.
AB  - OBJECTIVE: To determine whether prophylactic low dose aspirin (LDA) alone or in
      combination with low-molecular-weight-heparin (LMWH) reduces the recurrence of
      adverse pregnancy outcome (APO). STUDY DESIGN: In this retrospective cohort
      study, 84 consecutive multiparous patients with a previous history of severe
      preeclampsia (sPE) and intrauterine growth restriction (IUGR) (<10%ile) were
      assigned to receive no treatment, LDA alone, or LDA and LMWH. Odds ratios were
      calculated from logistic regression models. RESULTS: Combined LDA and LMWH
      significantly reduced the risk of developing IUGR in the index pregnancy (OR =
      0.16, 95% CI: 0.03-0.98). Among women with antecedent sPE (n=52), combined
      treatment reduced APO in the index pregnancy (OR = 0.08, CI: 0.01-0.96), IUGR (OR
      = 0.02, CI: <0.01-0.46), and IUGR with sPE (OR = 0.08, CI: 0.01-0.96).
      CONCLUSION: Combined treatment with LDA and LMWH is strongly protective against
      the development of APO in a cohort of women with antecedent APO.

PMID- 18320864
TI  - Update on ovarian hyperstimulation syndrome: part 2--clinical signs and
      treatment.
AB  - Patients with polycystic ovary syndrome (PCOS), hyperandrogenemia and
      hypothalamic ovarian dysfunction have a predisposition for developing ovarian
      hyperstimulation syndrome (OHSS). Choosing treatment protocols carefully,
      cautious stimulation, minimizing hCG dosages for ovulation induction, and
      refraining from embryo transfer in case of doubt, can markedly reduce the risk.
      In the treatment of moderate and severe hyperstimulation syndrome, adequate
      hydration with fluid balance, prophylaxis against thrombosis, ascites drainage
      when appropriate, and close monitoring and intensive-care monitoring if
      necessary, must be ensured. The aim of procedures in reproductive-medicine should
      be to achieve pregnancy rates that are as high as possible with as few side
      effects of the treatment as possible.

PMID- 18320865
TI  - Influence of adiposity on leptin, LH and androgen levels in lean, overweight and
      obese PCOS patients.
AB  - BACKGROUND: Leptin modulates hypothalamic-pituitary-gohadal axis functions.
      OBJECTIVE: To assess the influence of leptin on LH, and to investigate the
      potential association of leptin with body mass index (BMI) and androgen
      concentrations in women with polycystic ovary syndrome (PCOS). DESIGN: Levels of
      leptin, LH, FSH, E2, testosterone, and androstenedione were measured. PATIENTS:
      91 patients with PCOS were included in this study. METHODS: Patients were
      stratified into three groups according to BMI: normal weight (NW group, N=31),
      overweight patients (OW group N=30) and obese PCOS patients (Ob group, N=30).
      Results-Hyperandrogenemia was present in the studied group. A significant
      correlation was observed between BMI and androgens (both P < 0.01), and between
      leptin levels and androgens (respectfully for androstenendione P < 0.01 and for
      testosterone P < 0.05). A positive correlation between the LH and leptin levels
      in NW (P < 0.05) and OW (P < 0.001) patients was noticed, while negative
      correlation is seen in the Ob group (P < 0.01). In OW patients the significant
      positive correlation between leptin levels and androstenendione was found (P <
      0.001), after correction for BMI. A linear regression model indicated that leptin
      concentrations and BMI contributed negatively and significantly (P < 0.001) to LH
      concentrations. CONCLUSION: LH secretion in PCOS patients can be viewed as a
      consequence of the activity of different adipocyte and neuroendocrine factors.
      The attenuation in basal LH levels in obese PCOS women might be related to a
      leptin-resistant state.

PMID- 18320866
TI  - Value of fetal echocardiography in diagnosis of congenital heart disease in a
      Serbian university hospital.
AB  - OBJECTIVE: Ultrasound examination for each and every pregnancy is being accepted
      as a standard practice worldwide, and prenatal ultrasound diagnosis of congenital
      heart disease (CHD) is improving due to both staff education and ultrasound
      equipment modernization. The objective of this study was to estimate the value
      and accuracy of fetal echocardiography for diagnosis of fetal CHD in a large
      tertiary referral center for obstetrics and gynecology. METHODS: This study was
      based on a prospective follow-up of 27,051 consecutive patients at the Institute
      of Ob/Gyn, Belgrade, during 1999-2003. Out of this population a total of 517
      (1.9%) patients were selected for fetal echocardiography. The final diagnosis of
      congenital heart disease was confirmed or rejected on the basis of autopsy and
      histopathological findings, for the dead fetuses and newborns, or on the basis of
      neonatal echocardiography (followed by surgery/invasive diagnostic procedure),
      for the living neonates. RESULTS: From the total population analyzed, there was
      71 gravida (0.26%) with congenital fetal heart disease. In that study group, the
      most frequent cardiac anomalies were complex congenital heart diseases. Analyzing
      the outcome, there were 67.6% cases with fetal CHD who delivered live neonates.
      Out of the 73 fetuses/neonates with CHD, abnormal karyotype was detected in only
      9 cases. The parameters of the diagnostic value of fetal echocardiography were as
      follows: sensitivity 94.4%, specificity 99.8%, positive predictive value 98.5%,
      negative predictive value 99.1%, and overall diagnostic accuracy 99.0%.
      CONCLUSION: Fetal echocardiography has a very high diagnostic accuracy,
      commending referral of suspected patients to large tertiary referral centers.

PMID- 18320867
TI  - Climacteric symptom control after the addition of low-dose esterified conjugated
      estrogens to raloxifene standard doses.
AB  - INTRODUCTION: Hormone therapy (HT) is one the best options for climacteric
      symptom control; however when women are switched to raloxifene, after several
      years of HT, they restart with symptoms. OBJECTIVE: To evaluate the effect of the
      addition of low-dose esterified conjugated estrogens to the conventional dose of
      raloxifene in the control of climacteric symptoms. MATERIALS AND METHODS: 14
      healthy postmenopausal patients were studied. Climacteric symptoms were evaluated
      at baseline and 3 months after the beginning of treatment by the Kupperman's
      index (KI) and by the sum of the symptom evaluations carried out with an analog
      visual scale called SUMEVA. In all the anthropometric variables were documented,
      as well as time since menopause and endometrial thickness. At random they were
      distributed in some of the following groups: I) Raloxifene 60 mg/day (n=7) and
      II) Raloxifene 60 mg/day plus esterified conjugated estrogens 0.312 mg/day (n=7).
      STATISTICAL ANALYSIS: Differences among the groups, as well as those among
      baseline and those at the end of treatment, were determined by student's t test
      for independent samples and paired samples respectively. RESULTS: There were no
      differences in anthropometric variables, nor in the time since menopause. After
      three months of treatment the libido alterations vertigo and vaginal dryness were
      significantly greater in group I. In group II a significant decrease in hot
      flushes, insomnia, nervousness, vaginal dryness, KI, and SUMEVA were found, as
      was a significant increase in endometrial thickness. CONCLUSION: The treatment
      that is proposed in this study can constitute a temporary alternative during the
      period of transition from HT to raloxifene.

PMID- 18320868
TI  - A continuum of care model for postpartum hemorrhage.
AB  - The leading cause of maternal mortality is hemorrhage, generally occurring in the
      postpartum period. Current levels of PPH-related morbidity and mortality in low
      resource settings result from institutional, environmental, cultural and social
      barriers to providing skilled care and preventing, diagnosing and treating PPH.
      Conventional uterotonics to prevent PPH are typically not available or practical
      for use in low-resource settings. In such deliveries, most often taking place at
      home or in rural health centers, underestimation of blood loss leads to a delay
      in diagnosis. Deficiencies in communication and transportation infrastructure
      impede transfer to a higher level of care. Inability to stabilize a patient who
      is in hemorrhagic shock rapidly results in death. To address these individual
      factors, we propose a continuum of care model for PPH, including routine use of
      prophylactic misoprostol or other appropriate uterotonic, a standardized means of
      blood loss assessment, availability of a non-pneumatic anti-shock garment, and
      systemization of communication, transportation, and referral. Such a
      multifaceted, systematic, contextualized PPH continuum of care approach may have
      the greatest impact for saving women's lives. This model should be developed and
      tested to be region-specific.

PMID- 18320869
TI  - Umbilical cord rupture: a case report and review of literature.
AB  - The umbilical cord acts as a mechanical conduit between the fetus and placenta,
      allowing movement of water and nutrient substances between the fetal circulation
      and the amniotic fluid. Complications can occur antenatally or intranatally and
      are usually acute events that require immediate delivery to prevent intrauterine
      death. Even though the majority of the cord complications are unpreventable,
      significant improvement in perinatal mortality and morbidity can be achieved if
      such an event can be predicted. Umbilical cord rupture is not uncommon, but
      significantly underreported. We present an unusual cause of umbilical cord
      rupture and a review of literature.

PMID- 18320870
TI  - Fibroid volume, location and symptoms in women undergoing uterine artery
      embolization: does size or position matter?
AB  - OBJECTIVE: To investigate the relationship between MRI-determined uterine fibroid
      size and their location, and fibroid-related symptoms, including quality of life
      and sexual function, in women with symptomatic fibroids before uterine artery
      embolization (UAE). MATERIALS AND METHODS: Forty-six women underwent pelvic MRI
      within four weeks prior to UAE. The MRIs were analyzed and fibroid size and
      fibroid location were recorded. Women also completed a comprehensive self-report
      questionnaire within the four weeks prior to the procedure. The questionnaire
      (Short Form-36 (SF-36) and Female Sexual Function Index (FSFI), respectively,
      investigated the frequency of fibroid-related symptoms, as well as quality of
      life and sexual function. Pearson product moment correlation coefficients were
      used to examine relationships among variables, and ANOVAs were used to determine
      between-group difference. RESULTS: At baseline, women with symptomatic fibroids
      had worse quality of life and sexual function scores than healthy controls (p <
      .05). No fibroid-related symptoms, or aspects of quality of life or sexual
      function, were significantly correlated with either total uterine volume or
      largest fibroid volume. No significant differences with respect to fibroid
      related symptoms were found between patients with or without subserosal or
      submucosal fibroids. CONCLUSIONS: Women with symptomatic fibroids pre-UAE had
      impaired quality of life and sexual function, but size and location of fibroids
      as determined by MRI were not related to fibroid-related symptoms, health-related
      quality of life, or sexual function.

PMID- 18320871
TI  - The paradox of obstetric "near misses": converting maternal mortality into
      morbidity.
AB  - OBJECTIVE: To systematically review evidence of obstetric near-misses and their
      consequences. DATA SOURCES: PUBMED, OVID, and references of retrieved articles
      were used. METHODS OF STUDY SELECTION: Only 13 original articles describe the
      occurrence of obstetric/maternal near-miss morbidity to date. All were included
      in this review, in addition to other articles related to the epidemiology and
      consequences of severe acute maternal morbidity. TABULATION, INTEGRATION, AND
      RESULTS: Serious forms of maternal morbidity occur in about 1% of women in the
      United States compared to 3.01 to 9.05% in some developing settings. Worldwide,
      the leading causes of near-miss morbidity are hemorrhage and pregnancy-related
      hypertension or eclampsia/pre-eclampsia. These complications can have lasting
      effects, and their sequelae may result in maternal illness, injury and
      disability. Based on severity, we have provided three phenotypes of obstetric
      near-misses: Class I (near-miss with healthy infant); Class II (near-miss with
      feto-infant morbidity); Class III (near-miss with fetal/infant death).
      CONCLUSION: Obstetric near-misses should be considered as potentially chronic
      illnesses that warrant follow-up care because the theoretical cycle of near-miss
      (as postulated in this paper) can only be interrupted by the resolution of
      residual issues or the mother's death. Some may consider near-miss events to be
      obstetric successes because ultimately the mother's life was spared, but the
      consequences of these complications can be overwhelming and enduring.

PMID- 18320872
TI  - Facilitating physicians. As hospitals look to differentiate themselves in the
      eyes of admitting docs, robust physician information systems are growing in
      popularity.

PMID- 18320873
TI  - Prepping for ICD-10. A conversion with huge system ramifications, the move to ICD
      10 should be top of mind.

PMID- 18320874
TI  - The other ROI. Automating the release of information process can free up staff,
      save money and generally relieve headaches--but it takes IT to get there.

PMID- 18320875
TI  - Using WiFi to track clinical assets. Deciding to implement technology for
      tracking medical equipment is only the first question. Deciding which technology
      to use comes next.

PMID- 18320876
TI  - RIS rocks at RSNA. With workflow on everyone's minds, radiology information
      systems took center stage at imaging's super-conference.

PMID- 18320877
TI  - Piloting does to EMRs. Physicians hope CMS' EHR bonus project portends a broader
      shift in reimbursement priorities.

PMID- 18320878
TI  - Ante up. Partners HealthCare tells its network docs that an EMR is now stakes to
      play.

PMID- 18320879
TI  - Hospitals will underwrite EMRs for associated physician groups. Hospitals will
      increasingly leverage the combination of stark relaxations and ASP technology to
      bring physician groups EMRs.

PMID- 18320880
TI  - CIOs will need to support an array of mobile devices and applications. With no
      dominant applications, healthcare IT executives must provide clinicians with
      maximum flexibility for their mobile needs.

PMID- 18320881
TI  - A lack of data standards & sets will hamper information exchange. Healthcare CIOs
      must pressure government bodies and industry organizations to make true data
      standards a reality.

PMID- 18320882
TI  - Centralization will be key to image management. With skyrocketing storage needs,
      CIOs must work toward an image management strategy that hinges on centralization.

PMID- 18320883
TI  - Left unresolved, privacy issues will scuttle any attempts at HIE. As the desire
      to exchange health information between institutions grows, privacy issues must be
      addressed.

PMID- 18320884
TI  - Reimbursement & integration challenges will be solved as telehealth grows in
      importance. As the population ages and hospitals reach full capacity, integrating
      inpatient systems and telemedicine programs will be crucial.

PMID- 18320885
TI  - CIOs must develop strategic plans to support transparency initiatives. The coming
      data-transparency world of healthcare requires strong IT behind the scenes.

PMID- 18320886
TI  - As I.T. and clinical continue to blend, the role of CMIO will grow. Sitting at
      the nexus of healthcare and I.T., CMIOs are in a unique position to ensure both
      sides of the aisle are on the same page.

PMID- 18320887
TI  - Efficiently moving patients through the enterprise will be critical. Economic
      pressures and increased patient flow have forced CIOs to address patient
      throughput with I.T.

PMID- 18320888
TI  - Project management. The importance of project management in EMR implementations
      should never be undervalued.

PMID- 18320889
TI  - The real deal on EMR implementations. With ROI for large-scale IT projects still
      questionable, it's important to focus on quality improvements, not dollars and
      cents.

PMID- 18320890
TI  - Doing alerts right. Implemented correctly, alerts can greatly enhance a CPOE
      system, but done wrong, they can send physicians back to pens and paper.

PMID- 18320891
TI  - Price points. The demand for greater cost accountability challenges payers and
      care providers to supply enough data for informed decision-making.

PMID- 18320892
TI  - Alberta's action plan for nurse recruitment and retention.

PMID- 18320893
TI  - Cultural kitchens: changing the power balance.

PMID- 18320894
TI  - A nurse's insight, a cancer patient's shoes.

PMID- 18320895
TI  - Military nursing. 1917.

PMID- 18320896
TI  - Promoting safe exercise and foot care for clients with type 2 diabetes.
AB  - Exercise is a cornerstone in the management of type 2 diabetes. However, those
      who have neuropathy as a complication of the disease may have decreased
      capacities for exercise and a greater need for exercise instruction and
      monitoring. The author conducted a study with a random sample of elderly adults
      with type 2 diabetes to examine how the presence of neuropathy affects exercise
      participation in this group. Among the 427 respondents, those with neuropathy had
      significantly lower scores for health functioning and for positive beliefs about
      exercise than those without this complication. They also had significantly higher
      scores for the receipt of diabetes-specific exercise education and knowledge;
      perceived barriers to exercise; and exercise-related injuries, including foot
      injuries. Nurses need to ensure they use a health promotion and prevention
      approach with their clients with diabetes by promoting safe, appropriate exercise
      and educating clients about proper foot care.

PMID- 18320897
TI  - A public health nursing initiative to promote antenatal health.
AB  - At least one in 10 pregnant women experiences depression. Other health risks
      during pregnancy include family violence, substance abuse, inadequate nutrition,
      financial challenges, environmental hazards and lack of social support. Public
      health nurses are in a unique position to enhance perinatal health by assessing
      for antenatal psychosocial risk factors. During 2005-06 in a suburban/rural
      community near Edmonton, Alberta, public health nurses initiated a one-year
      demonstration project with the goal of increasing the number of health and
      community services accessed by pregnant women as a result of an interactive
      appointment with a public health nurse. Eight family physicians in WestView
      Primary Care Network and three midwives from WestView's Shared Care Maternity
      Program referred local pregnant clients to the public health nursing unit at
      WestView Health Centre in Stony Plain. Each woman was assessed by a public health
      nurse for a variety of psychosocial risk factors. Results of the assessment
      determined the type of additional health services to which the pregnant women
      were referred. Care providers were unanimous in their support for public health
      nurses' continuing to provide antenatal assessments to an expanded population of
      suburban/rural communities in the Capital Health region.

PMID- 18320898
TI  - Kay Matthews: a labour of love. Interview by Tara Tosh-Kennedy.

PMID- 18320899
TI  - Tensorial description of the geometrical arrangement of the fibrous molecules in
      vascular endothelial cells.
AB  - This work presents a tensorial description of the geometrical arrangement of the
      cellular molecules in the vascular endothelial cells. The geometrical arrangement
      of the molecules is the foundation of the mechanical properties of the molecular
      aggregates, which are the foundation of the physical behavior of the cells and
      tissues. For better studying the physical behavior of the cells and tissues, the
      geometrical arrangement of the cellular molecules has to be described
      quantitatively. In this paper, a second order molecular configuration tensor
      P(g)ij for fibrous protein in the cells is defined for quantitative measurement.
      Here, the subscripts i, j refer to the coordinate axes x1, x2, x3, and the
      superscript g refers to the kind of fibrous protein. Every molecular
      configuration tensor P(g)ij has 9 components. To give an example, the F-actin
      fibers in the vascular endothelial cells were studied. These molecules were
      stained with phalloidin and observed in a confocal microscope. Digitized images
      of the F-actin fibers were analyzed to determine the F-actin's molecular
      configuration tensor P(g)ij. The tensor P(g)ij is a simple and definitive
      description of a complex system of molecules which are important in the research
      on tissue remodeling of blood vessels. In this article, the P31 and P32 values in
      the P(g)ij tensor of F-actin fiber in the endothelial cells in rat's abdominal
      aorta were obtained, and the distributions of these two components in the
      endothelial cells were presented. The molecular configuration tensor P(g)ij can
      be applied to other fibrous proteins in the cells and to cells other than
      vascular endothelial cells.

PMID- 18320900
TI  - A multiscale probabilisitic framework to model early steps in tumor metastasis.
AB  - Tumor metastasis is the leading cause of nearly all cancer related deaths. While
      several experimental and computational studies have addressed individual stages
      of the complex metastasis process, a comprehensive systems-biology model that
      links various stages of metastasis has not been put forth as of yet. In this
      paper we discuss the formulation and application of such a model that utilizes
      basic principles of cell biology, physics and mechanics to study the migratory
      patterns of tumor cells as they move from the parent tumor site to the connective
      tissue via the basement membrane. The model is first of its kind in capturing the
      essential early features of metastasis in a single simulation and shows good
      agreement with recent experimental studies.

PMID- 18320901
TI  - Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists.
AB  - Obesity is a risk factor for asthma. The purpose of this study was to determine
      whether metformin, an agent used in the treatment of an obesity-related condition
      (type II diabetes), might have therapeutic potential for modifying the effects of
      obesity on airway smooth muscle (ASM) function. Metformin acts via activation of
      AMP-activated protein kinase (AMPK), a cellular sensor of energy status. In
      cultured murine ASM cells, metformin (0.2-2 mM) caused a dose-dependent
      inhibition of cell proliferation induced by PDGF (10(-8) M) and serotonin (10(-4)
      M). Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-Driboruranoside
      (AICAR), also inhibited PDGF-induced proliferation. Furthermore, cells treated
      with metformin or AICAR, also exhibited an attenuation in the rate of
      cytoskeletal remodeling, as quantified by spontaneous nanoscale motions of
      microbeads tightly anchored to the cytoskeleton (CSK) of the ASM cell. ASM cells
      treated with metformin or AICAR, however, exhibited no appreciable differences in
      stiffness as measured by optical magnetic twisting cytometry (OMTC) or their
      abilities to stiffen in response to contractile agonist serotonin. Taken
      together, these findings suggest that metformin, probably through activation of
      AMPK, reduces the rate of ongoing reorganization of the CSK and inhibits ASM cell
      proliferation.

PMID- 18320902
TI  - Two-layer passive/active anisotropic FSI models with fiber orientation: MRI-based
      patient-specific modeling of right ventricular response to pulmonary valve
      insertion surgery.
AB  - A single-layer patient specific right/left ventricle patch (RV/LV/Patch)
      combination model with fluid-structure interactions (FSI) was introduced in our
      previous papers to evaluate and optimize human pulmonary valve
      replacement/insertion (PVR) surgical procedure and patch design. In this paper,
      an active anisotropic model with two-layer structure for ventricle wall and
      tissue fiber orientation was introduced to improve previous isotropic model for
      more accurate assessment of RV function and potential application in PVR surgery
      and patch design. A material-stiffening approach was used to model active heart
      contraction. The computational models were used to conduct "virtual
      (computational)" surgeries and test the hypothesis that a PVR surgical design
      with a smaller patch and more aggressive scar tissue trimming would lead to
      improved RV cardiac function recovery. Results from our models validated by pre
      operation data indicated that the small patch design had 11% improvement in RV
      function as measured by RV ejection fraction, compared to the conventional patch.
      Maximum Stress-P1 value from the active anisotropic model was 121.2% higher than
      that from the passive isotropic model. Computational RV volume predictions agreed
      well with CMR-measured volume data (error < 2%).

PMID- 18320903
TI  - Whither patient-centered care?

PMID- 18320904
TI  - EBP by any other name is still a rose.

PMID- 18320906
TI  - Effects of patient-centered care on patient outcomes: an evaluation.
AB  - The purposes of this study were to determine the extent to which acute care nurse
      practitioners (ACNPs) provide patient-centered care (PCC) and to explore the
      effects of PCC on patients' functional status, self-care ability, and
      satisfaction with care. A nonexperimental design with repeated measures was used.
      The sample included 320 patients with acute medical and surgical conditions.
      Patients perceived that ACNPs provided PCC, operationalized as encouraging
      patients to participate in care and individualizing care to a moderate extent.
      Implementation of these PCC components was positively associated with some
      domains of self-care ability and satisfaction with care. Further investigation of
      the contribution of PCC to outcomes is recommended.

PMID- 18320905
TI  - In the margins of the mind: development of a projective research methodology for
      the study of nursing practice.
AB  - This article presents an original research method derived from the Thematic
      Apperception Test used in clinical psychology to understand human motivation and
      action. The research method is derived from the theory of projection, which
      states that humans will perceive stimuli in terms of their own expectations and
      motives and will credit others with their own attitudes, beliefs, traits, and
      dispositions. Projective techniques are one of a handful of methods that provide
      access to this type of knowledge since it resides below the level of
      consciousness. Use of this type of method in nursing research may be fruitful
      because of its capacity to make apparent the complex interplay between a
      clinician's beliefs and the interpretation of meaning that motivates clinical
      action.

PMID- 18320907
TI  - Event-oriented data integration: a qualitative strategy in studying professional
      practice.
AB  - The purpose of this article is to present a qualitative mixed-method strategy
      that uncovers the compound reality in professional practice and the inner aspects
      of actions, feelings, values, and thoughts embedded therein. The authors
      developed a systematic strategy for collecting and handling data from different
      sources. This strategy, called event-oriented data integration represents within
      method triangulation as well as triangulation during data analysis. The analysis
      involves 2 distinctive new steps for structuring of data--the braiding of data
      threads and the braiding of data ropes. We found that the process of weaving
      together different data created an inclusive text that allowed the researcher to
      undertake a holistic, coherent, and consistent analysis and to attain a more
      complete picture of professional practice.

PMID- 18320908
TI  - "Only a manic depressive!": the zone of the untouchable and exceeding limits in
      acute psychiatric care.
AB  - This article addresses psychotic patients' fragile boundaries and need for
      professional help to restore their personal untouchable zone. We examine how
      nurses move into this inviolable zone and re-establish limits. Empirical data are
      drawn from an acute psychiatric setting and focus on one patient in different
      situations and on her relationships with nurses. Data from nurses' discussions
      and the researcher's experience are also included. The concept of the zone of the
      untouchable, by the Danish theologian and philosopher K. E. Logstrup, guides
      interpretation. Analysis shows how and with which critical and constructive
      consequences the diagnosis-oriented understanding affects the patient-nurse
      relationship. Conclusions include premises that can guide nurses moving into the
      patient's untouchable zone.

PMID- 18320909
TI  - Yellow birch.

PMID- 18320910
TI  - Allergies to sulfonamide antibiotics and sulfur-containing drugs.
AB  - OBJECTIVE: To provide a literature review and clinical summary of the evaluation
      and management of sulfonamide drug reactions. DATA SOURCES: Published English
      language medical literature. STUDY SELECTION: Selected trials of drug
      desensitization protocols. RESULTS: Obtaining a detailed history is invaluable in
      assessing a history of reactions to sulfonamide medications, because allergy to
      these drugs remains a clinical diagnosis at present. Numerous efficacious drug
      desensitization protocols for management have been published and are reviewed in
      detail. CONCLUSIONS: The term sulfa allergy is imprecise and misleading and
      therefore should be discouraged. There are important distinctions between
      sulfonylarylamines (antimicrobial sulfonamides), nonarylamine (nonantimicrobial)
      sulfonamides, and sulfones, with regard to allergic and other adverse drug
      reactions. Most reactions to sulfonylarylamines probably result from
      multifactorial immunologic and toxic metabolic mechanisms, whereas less is known
      about the precise mechanisms of reactions to other sulfur-containing drugs.

PMID- 18320911
TI  - Self-reported quality of life among inner-city youth with asthma: an empirical
      examination of the PedsQL 3.0 Asthma Module.
AB  - BACKGROUND: Asthma disproportionately affects African American youth and may
      significantly impair their daily functioning. Although a number of self-reported
      health-related quality of life (HRQoL) measures have been developed, many rely on
      parent proxy report rather than youth self-report. Few validity studies have been
      undertaken to evaluate youth self-report instruments, and studies of economically
      disadvantaged ethnic minority populations are particularly lacking. OBJECTIVE: To
      examine the psychometric properties of the PedsQL 3.0 Asthma Module, a widely
      available self-report index of HRQoL in a sample of inner-city African American
      youth. METHODS: Seventy African American youth with asthma (age range, 9-17
      years) and their primary caregivers participated. Youth completed the PedsQL 3.0
      Asthma Module (developed for youth aged 5-18 years), whereas caregivers provided
      reports of youth HRQoL, asthma symptoms, health care use, and school absences.
      Ratings of asthma severity were obtained via physician rating and spirometry.
      RESULTS: The PedsQL 3.0 Asthma Module total and subscale scores evidenced
      adequate internal consistency (alpha values >.70), convergent validity with
      parent proxy ratings of HRQoL and other indexes of functional impairment and
      differentiated between youth with greater and lesser disease severity.
      CONCLUSION: HRQoL can be reliably assessed using the self-report form of the
      PedsQL 3.0 Asthma Module among 9- to 17-year-old African American youth from
      economically disadvantaged backgrounds.

PMID- 18320912
TI  - Development of a Web-based questionnaire to collect exposure and symptom data in
      children and adolescents with asthma.
AB  - BACKGROUND: Questionnaires are an important component of epidemiologic studies.
      Maintaining compliance in longitudinal studies is a challenge, particularly from
      children and adolescents. OBJECTIVE: To implement a Web-based questionnaire for
      children and adolescents with asthma for daily self-completion, minimizing recall
      bias and maximizing compliance. METHODS: We determined symptoms, exposure to
      asthma triggers, peak expiratory flow rate, and medications taken, including dose
      and dose time. The Web-based system can be less time-consuming and a source of
      fewer errors than paper questionnaires and permits review of the data and
      compliance during the study. The Web programming of the questionnaire included
      branching, so that questions deemed irrelevant based on a previous response were
      not presented to participants, minimizing the completion time. RESULTS: Sixty
      four students with asthma participated nearly daily for between 2 and 4 months.
      Financial incentives for the participants were calculated in real time based on
      completion rates. Monitoring of the subject's completion included an extensive
      administrative hierarchical alert system, enabling the staff to target
      individuals who fell behind in entries and needed the most encouragement.
      CONCLUSIONS: Similar compliance and completion rates were obtained using the Web
      based questionnaire as reported for smaller paper questionnaires by parents of
      children. The Web-based system provides a mechanism to obtain daily responses
      directly from an age group not often accessible by traditional questionnaire
      approaches.

PMID- 18320913
TI  - Race/ethnicity, language, and asthma care: findings from a 4-state survey.
AB  - BACKGROUND: Latino and African American children have poorer asthma control than
      non-Latino white children, but few studies examine the association among
      race/ethnicity, language, and specific processes of asthma care. OBJECTIVE: To
      evaluate the association of race/ethnicity and language with the quality of
      asthma care. METHODS: A random sample of children from birth to the age of 17
      years with asthma within 4 states (California, Texas, Illinois, and Alabama) was
      selected for the National Asthma Survey conducted by the National Center for
      Health Statistics from March 1, 2003, to March 10, 2004. Parents completed a
      telephone survey that included measures of asthma care quality. The final sample
      was 1,517 children. RESULTS: According to parental report, only 41.4% of children
      had an asthma management plan and 48.5% were ever advised by a clinician to
      control asthma by changing the child's home and school environment. African
      American and Latino children with persistent asthma had lower odds of taking
      controller medication than non-Latino white children. In multivariate analysis
      adjusting for annual income, insurance, and age, Latino children with Spanish
      parental interview, but not African American and Latino children with English
      parental interview, had poorer experiences with care than white children (ever
      taught what to do during an attack: odds ratio, 0.4 [95% confidence interval, 0.2
      0.6]; and ever advised to change child's home and school environment: odds ratio,
      0.5 [95% confidence interval, 0.3-0.8]). CONCLUSIONS: Differences in asthma care
      quality and controller use persist among racial/ethnic and language groups
      despite similar rates of planned encounters for asthma. Improving use of
      controller medications and counseling on environmental modifications are
      important for reducing asthma disparities.

PMID- 18320914
TI  - Gene-environment interactions between CD14 C-260T and endotoxin exposure on
      Foxp3+ and Foxp3- CD4+ lymphocyte numbers and total serum IgE levels in early
      childhood.
AB  - BACKGROUND: Innate immune system stimuli, such as endotoxin, seem to affect
      allergy risk. Previously, we described gene-environment interactions between the
      endotoxin receptor polymorphism C-260T of the CD14 gene and endotoxin exposure on
      total serum IgE level; however, the mechanism of this interaction is not known.
      OBJECTIVE: To examine whether this gene-environment interaction affects early
      CD4(+)Foxp3(-) or CD4(+)Foxp3(+) lymphocyte numbers. METHODS: Participating
      children were part of a birth cohort in the Detroit metropolitan area.
      Participants were genotyped for the CD14 C-260T polymorphism. Endotoxin exposure
      was estimated from dust measured in the home when children were 6 months old.
      Intracellular Foxp3 protein expression, a regulatory T-cell marker, was used to
      characterize CD4(+) lymphocytes in blood samples collected at the age of 12
      months; total serum IgE level was also measured at this time. Because
      race/ethnicity may confound or modify genetic associations, all analyses were
      stratified by race/ethnicity. RESULTS: We observed a significant gene-environment
      interaction between CD14 C-260T genotype and endotoxin exposure on CD4(+)
      lymphocyte numbers, particularly CD4(+)Foxp3(-) lymphocytes. Stratified analyses
      suggest effect modification by race/ ethnicity on CD4(+)Foxp3(+) lymphocyte
      numbers, with a significant interaction in African American children but not in
      white children. The interaction between CD14 C-260T genotype and endotoxin
      exposure on total IgE levels was opposite that observed for CD4(+) lymphocyte
      numbers, suggesting reciprocal relationships. CONCLUSIONS: A gene-environment
      interaction between endotoxin and CD14 C-260T genotype on IgE levels may be the
      result of an upstream, opposing effect on CD4(+)Foxp3(+) and CD4(+)Foxp3(-)
      lymphocyte numbers. Race/ethnicity may affect which of these cell populations is
      affected by this gene-environment interaction.

PMID- 18320915
TI  - European allergen extract units and potency: review of available information.
AB  - BACKGROUND: There is considerable variability in how allergen extract potency is
      measured and reported worldwide. In Europe, where many sublingual immunotherapy
      studies have been conducted, manufacturers report allergen extract potency as
      units based on an in-house reference, making it difficult to understand the exact
      doses used and to compare studies. OBJECTIVES: To describe the various methods of
      expressing extract potency that European allergen extract manufacturers use and
      to gather reports on the micrograms of major allergen of the in-house units of
      European allergen extract manufacturers. METHODS: Information was derived from 3
      sources: data on extract potency in micrograms of major allergen in articles on
      sublingual immunotherapy found by PubMed (references through October 2005) and in
      reference articles, brochures on allergen extracts from the manufacturers, and
      information provided by structured questionnaires e-mailed to the manufacturers.
      RESULTS: All but 1 of the European allergen extract manufacturers use in-house
      reference standards that are based on titrated skin prick testing of allergic
      patients. Subsequently, in vitro tests compare the potency of commercial batches
      with the in-house reference and potency is assigned as arbitrary units. Most
      manufacturers measure major allergen content of their standardized products but
      do not release this information with the package insert. Diversity in major
      allergen content was found. CONCLUSIONS: Micrograms of major allergens given in
      articles on sublingual immunotherapy to express the dose administered cannot be
      used to translate the dose to US extracts. Extract potency can only be compared
      if uniform test methods and reference extracts are used.

PMID- 18320916
TI  - Formoterol fumarate inhalation powder vs albuterol nebulizer for the treatment of
      asthma in the acute care setting.
AB  - BACKGROUND: Although albuterol remains the standard treatment for asthma in the
      emergency department, formoterol fumarate may be more advantageous, with its
      rapid and long-lasting bronchodilation. OBJECTIVE: To compare formoterol fumarate
      with albuterol in controlling acute asthma exacerbation. METHODS: Patients aged
      18 to 65 years who presented to the emergency department with mild to moderate
      asthma exacerbation (peak expiratory flow rate [PEFR], 40%-60% of predicted) were
      randomized to receive either formoterol fumarate aerolizer (12 microg) or
      albuterol nebulizer (2.5 mg) every 30 minutes up to 2 treatments. Symptom scores
      and PEFRs were measured at each treatment. RESULTS: Thirty-four patients (19 in
      the albuterol arm and 15 in the formoterol fumarate arm) were enrolled. At 30 and
      60 minutes, the mean PEFR of the albuterol group increased from 43.7% of
      predicted to 51.9% of predicted and 54.6% of predicted, respectively, and the
      formoterol fumarate group had changes in the mean PEFR from 49.3% of predicted to
      55.5% of predicted and 57.3% of predicted, respectively, and the mean change in
      the 2 groups was not significantly different at 30 and 60 minutes (P = .64 and
      .57, respectively, by t test). The albuterol group improved in symptom scores by
      3.7 and 5.5 from 0 minutes to 30 and 60 minutes, respectively, and in the
      formoterol fumarate group these values were 3.1 and 4.9 at 30 and 60 minutes,
      respectively, and the mean change in the 2 groups was not significantly different
      at 30 and 60 minutes (P = .61 and .76, respectively, by t test). CONCLUSION:
      Formoterol fumarate is as effective as albuterol inhalation for the treatment of
      adults with mild to moderate asthma exacerbations in the acute care setting.

PMID- 18320917
TI  - Benefits and risks of danazol in hereditary angioedema: a long-term survey of 118
      patients.
AB  - BACKGROUND: Hereditary angioedema (HAE) due to C1 inhibitor deficiency is
      clinically characterized by relapsing skin swellings, abdominal pain attacks, and
      life-threatening upper airway obstruction. Treatment with androgens prevents
      attacks for those with this condition. OBJECTIVE: To examine the benefits and
      risks of long-term treatment with danazol. METHODS: Data were generated
      retrospectively from 118 German and Danish patients who had HAE due to C1
      inhibitor deficiency and were treated with danazol from 2 months to 30 years. The
      frequency and severity of acute attacks were registered before and during danazol
      treatment, and adverse effects to the treatment were noted. Data were collected
      by using standardized questionnaires. RESULTS: In all, 111 of 118 patients
      responded to danazol. During treatment, 54 of the 118 patients (45.8%) became
      symptom free or had 1 attack or less per year. In the other patients, hereditary
      angioedema ran a mild course. The frequency of acute attacks during danazol
      treatment was reduced to 16.2%, and the attacks were considerably milder than
      before treatment. Laryngeal edema was reduced to 4.8%. Adverse effects (weight
      gain, virilization, menstrual irregularities, headache, depression, and/or liver
      adenomas) occurred in 93 of the 118 patients and led to discontinuation of
      danazol therapy in 30 patients. CONCLUSIONS: Danazol is highly beneficial in
      patients with frequent and severe attacks of HAE. Because the risk of adverse
      effects is high, close monitoring of patients is mandatory. However, many
      patients accept the adverse effects of prophylactic treatment to avoid the
      distressing and sometimes life-threatening attacks of this condition.

PMID- 18320918
TI  - Long-term efficacy of venom immunotherapy.
AB  - BACKGROUND: The long-term efficacy of venom immunotherapy (VIT) in patients who
      either prematurely discontinue VIT or who experience subsequent stings after
      discontinuation of VIT remains uncertain. OBJECTIVE: To survey sting reaction
      patterns in patients who had previously discontinued VIT. METHODS: Patients who
      had received VIT between January 1, 1984, and December 31, 2004 were sent a
      questionnaire inquiring whether they had been stung by an insect to which the VIT
      had been directed. Symptoms that developed were assessed. The patients were
      subsequently contacted by telephone to clarify their responses. RESULTS: Of 227
      patients who responded to the questionnaire, 181 (79.7%) received VIT for more
      than 3 years; 100 of these 181 patients (55.2%) were stung after discontinuing
      VIT. At the time of the first sting after stopping VIT, 92 patients had a local
      reaction and 8 had a systemic reaction. Of 40 patients who were stung more than
      once after ending VIT, 7 (17.5%) experienced reactions of greater severity with
      the subsequent stings. All the patients reported that their reactions after
      ending VIT were milder than before treatment. The likelihood of systemic
      reactions to stings was almost identical in patients treated for either longer or
      shorter than 3 years with VIT. CONCLUSIONS: In most patients, VIT provides long
      term protection from severe systemic reactions. Risk of systemic reactions
      increases with subsequent stings after ending VIT. All the patients reported that
      symptoms experienced with stings after stopping VIT were milder than symptoms
      before VIT.

PMID- 18320919
TI  - Assessment of protein antibody response in patients with suspected immune
      deficiency.

PMID- 18320920
TI  - A novel mutation associated with autoimmune polyendocrinopathy-candidiasis
      ectodermal dystrophy.

PMID- 18320921
TI  - Adult-onset periodic fever, aphthous stomatitis, pharyngitis, and adenitis.

PMID- 18320922
TI  - Exercise-induced hyperventilation.

PMID- 18320923
TI  - Episodic angioedema with eosinophilia: successful treatment with imatinib.

PMID- 18320924
TI  - Hypotension from epinephrine in a food-allergic patient with long QT syndrome.

PMID- 18320925
TI  - Hycor Turbo-MP specific IgE assay performance.

PMID- 18320926
TI  - Are we following practice parameter guidelines on allergen immunotherapy?

PMID- 18320927
TI  - [Guidelines for the clinical practice: aesthetic and functional rhinoplasty].
AB  - A multidisciplinary working group of experts met in 2006 in order to establish a
      list of recommendations concerning the aesthetic and functional rhinoplasties.
      These experts tried to answer various practical problems while relying, on one
      hand, on a critical analysis of the literature, and on the other hand, on a
      consensus within the group. Six topics were approached. The management of the
      preoperative consultation, the surgical environment, the contra-indications, the
      materials used, the management of the post operative period, some particular
      pathological situations. This collective reflexion thus did not relate to the
      surgical techniques but to the methodology of treatment of patients who are
      candidates for rhinoplasty. It comes out clearly from this collective work that
      surgical indication can only be addressed after having clarified all the
      technical and psychological aspects. The use of computer graphics is recommended.
      Cartilage autograft are recommended as a priority.

PMID- 18320928
TI  - [Characteristics of the consultation in medicine and/or plastic surgery].
AB  - Consultation in medicine and/or plastic surgery presents specific elements which
      must first be organized. These characteristics concern the location of exercise
      and both the reception and the ancillary medical staff The consultation requires
      a different listening from a consultation for another reason. The psychological
      aspect is of primary importance here. The photographs are essential as well as
      information and enlightened assent. A relation of confidence, the technical skill
      of the doctor and his team which must discrete, combined with accessible
      buildings, will be the assets of a successful aesthetic consultation and a
      treatment which will satisfy the patient.

PMID- 18320929
TI  - [Analysis of the projection of the nasal tip].
AB  - The success of a rhinoplasty is conditioned by a detailed preoperative analysis
      of the morphology of the nose and face of the patient. A good knowledge of the
      characteristic reference marks and nasal proportions authorize a detailed
      description of the nose. The position of the nasal tip is one of the principal
      characteristics of the nose. It is expressed by the combination of its projection
      and its height. A reflexion on the position of the tip and its ideal position
      post-operatively enabled us to work out a conceptual approach aiming at guiding
      the surgical project. The drawing of two circles centered on the nasal pyramid is
      the expression of this concept. Thus, a detailed analysis of the nasal pyramid
      and a biomechanical approach are the key to a relevant surgical plan.

PMID- 18320930
TI  - [Artistic anatomy of the nose: proposals for a simplified project of
      rhinoplasty].
AB  - OBJECTIVE: The authors developed an original and simple method of evaluation of
      the aesthetic lines of the nose adapted to the harmony of the face. METHOD:
      Initially based on their experience, the authors propose an evaluation of the
      nose in 2 stages and 5 sequencies based on the construction of single circuit
      lines according to various incidences. They checked thereafter the validity of
      this method on the operative project and on the appreciation of the results of
      the rhinoplasties. RESULTS: Controlled on several types of faces, the method
      suggested by the authors proved to be reliable, simple, reproducible. CONCLUSION:
      The authors proposed a method of evaluation of the aesthetic lines of the nose
      integrated to the harmony of the face. This method relies on the construction, in
      5 stages, of single circuit lines not requiring any particular material. The
      artistic method of evaluation of the nose proposed by the authors is very simple.
      Rapid and immediately usable, it makes it possible to schedule a rhinoplasty in a
      few minutes. The evaluation of the aesthetic results of the rhinoplasties is also
      very simple and reproducible. It has moreover the merit to propose a model of
      teaching making it possible to the rhinoplastician to criticize his results and
      thus to progress in its technical training and its operational indications.

PMID- 18320931
TI  - [Analysis of the possibilities for reconstruction of partial nasal tissue loss].
AB  - The surgical reconstruction of the nasal pyramid requires a precise analysis of
      the position, dimension and depth of the loss of substance. The means usable are
      numerous and the author gives his personal approach on the techniques which he
      generally carries out. In cancerology it is of course necessary to preliminarily
      perform a sufficiently broad excision before reconstruction. The plastic surgery
      must be done plane by plane with tissue of equivalent quality. Osseointegrated
      epistheses are to be reserved for particular cases when reconstructive plastic
      surgery cannot be proposed for local or general reasons.

PMID- 18320932
TI  - [Eye rings: morphological classification and treatment].
AB  - Eye rings are multifactorial so a combined treatment is often thought. The
      discoloration of the skin, the border between thin and thick skin, the
      skeletonisation, the eye rings accentuated by fat pads are an entity making the
      approach to treatment far more complex. The morphological classification proposed
      by the author based on face and profile analysis, permits a standardized
      treatment. Now our possibilities are more medical, non invasive and less
      surgical.

PMID- 18320933
TI  - [The relevance of Choukroun's platelet rich fibrin (PRF) during facial aesthetic
      lipostructure (Coleman's technique): preliminary results].
AB  - OBJECTIVES: To evaluate the interest of fibrin PRF clots, a concentrate of
      platelets and immune factors, for the optimization of the adipocyte graft
      according to the technique of facial lipostructure described by S. Coleman.
      MATERIALS AND METHODS: Between May 2005 and June 2006, 32 patients (7 men and 25
      women) benefited from a Coleman lipostructure with the use of PRF. The average
      age was 59 years (39 to 72 years). Lipostructure was used alone in 22 patients
      and associated with a face lift and/or a blepharoplasty in 10 patients. Before
      the adipocyte graft, a mixture of PRF and greasy supernatant (resulting from the
      purification of the sample of adipocytes) is deposited on the zones to be grafted
      in the same way as for lipostructure. For 2 patients, the pretreatment of the
      site to be grafted with PRF was unilateral. Patients were followed-up for one
      year. RESULTS: In this series, all the patients were satisfied with the result
      with minimal associated resorptions. No massive resorption requiring a resumption
      of lipostructure was noted. In the 2 patients treated with unilateral use of PRF,
      one notes a light asymmetry, the hemi-face treated with PRF appearing more stable
      than the side without PRF. No important residual oedema or echymosis were seen on
      the 3rd post-operative week. CONCLUSION: By offering a matricial support to
      angiogenesis and by stimulating the proliferation of pre-adipocytes, the PRF
      could have a beneficial role on the cicatrization and the consolidation of an
      adipocyte graft. Further studies are necessary to validate the interest of the
      PRF during aesthetic lipostructures. The potential uses in plastic surgery of
      such a biomaterial, easy and fast to produce, without any overcost and with no
      risk, are very numerous and require from now on to be tested and validated
      methodically.

PMID- 18320934
TI  - [Aesthetic parotidectomy: face lift incision and SMAS flap].
AB  - INTRODUCTION: Traditional parotidectomy skin incision (bayonet-shaped incision)
      is adapted from an extirpative standpoint but not ideal cosmetically. There are
      three main drawbacks: Scar, retro-mandibular depression and Frey syndrome. The
      goal of this prospective study was to evaluate the feasibility of this facial
      incision for extirpative purposes and to define the clinical benefit in terms of
      scar and retromandibular depression. METHOD: Ten patients with parotid tumors
      were included during the period 2005-2006. All patients had benign tumours: 5
      males and 5 females. Mean age was 49 yrs. (42-67). Investigated parameters were:
      "retromandibular depression", "skin scar" and "Frey syndrome". Analogic visual
      satisfaction scale (1-10) was used by patients to assess these data
      postoperatively at 15 days, 1 month and 6 months. RESULTS: This face lift
      approach allowed very good surgical exposure not only of the parotid area but the
      posterior submandibular region and over the sternocleidomastoid muscle.
      Postoperative lateral facial contour was symmetric and good in all cases. Six
      patients assessed this parameter 8/10 and 4 assessed 10/10. After removal of
      stitches the facial skin scar was considered good in 100% of cases. Six patients
      assed this parameter 9/10 and 4 assessed 10/10. No Frey syndrome was reported by
      any patients within 16 months postoperatively. CONCLUSION: Association of a face
      skin lift approach and a SMAS flap yields a very good cosmetic outcome after
      surgical parotidectomy. As aesthetic considerations are obvious in breast
      surgery, aesthetic considerations have a great place in parotid and head and neck
      surgery.

PMID- 18320935
TI  - The balance between NRTI discrimination and excision drives the susceptibility of
      HIV-1 RT mutants K65R, M184V and K65r+M184V.
AB  - The HIV-1 reverse transcriptase (RT) resistance mutations K65R and M184V occur
      individually and in combination, and can contribute to decreased treatment
      responses in patients. In order to understand how these mutations interact with
      one another to confer drug resistance, the susceptibilities and underlying
      resistance mechanisms of these mutants to nucleoside RT inhibitors (NRTIs) were
      determined. Virus carrying K65R have reduced susceptibility to most NRTIs, but
      retain full susceptibility to zidovudine (AZT). M184V mutants have reduced
      susceptibility to lamivudine (3TC), emtricitabine (FTC) and didanosine (ddl), and
      contribute to reduced susceptibility to abacavir; however, they remain fully
      susceptible to tenofovir (TFV), AZT and stavudine (d4T). In cell culture, the
      K65R+M184V virus showed slightly increased susceptibility to TFV, AZT and d4T
      compared with K65R alone, but showed further decreases in susceptibility to 3TC,
      FTC, ddl and abacavir. There are two major biochemical mechanisms of resistance:
      altered NRTI binding/incorporation and altered NRTI excision after incorporation.
      For most NRTIs, the primary mechanism of resistance by K65R, M184V and K65R+M184V
      mutant RTs is to disrupt the NRTI-binding/incorporation steps. In the case of
      AZT, however, decreased binding/incorporation by K65R and K65R+M184V was
      counteracted by decreased AZT excision resulting in wild-type susceptibility. For
      TFV, decreased excision by K65R and K65R+M184V may partially counteract the K65R
      driven decrease in incorporation relative to wild-type resulting in only low
      levels of TFV resistance. The K65R-mediated effect on decreasing NRTI excision
      was stronger than for M184V. These studies show that both mechanisms of
      resistance (binding/incorporation and excision) must be considered when defining
      resistance mechanisms.

PMID- 18320936
TI  - Influenza A (H1N1) virus resistance to cyanovirin-N arises naturally during
      adaptation to mice and by passage in cell culture in the presence of the
      inhibitor.
AB  - Influenza A/New Caledonia/20/99 (H1N1) virus was studied for development of
      resistance to cyanovirin-N (CVN). CVN neutralizes virus infectivity by binding to
      specific high-mannose oligosaccharides on the viral haemagglutinin 1 (HA1)
      subunit. During virus adaptation to mice in the absence of CVN treatment the
      virus became resistant to CVN (CVN-MR virus), as did virus passaged in cell
      culture in the presence of CVN (CVN-R virus). The CVN-R virus possessed a single
      amino acid change at position 94a (Asn94aAsp) of HA1 that eliminated this
      glycosylation site. The CVN-MR virus at mouse passage 7 was a mixture of clones,
      consisting of a single mutation (Asp225Gly) and double mutations
      (Asn63Ser+Asp225Gly or Asn94a+Asp225Gly), eliminating glycosylation sites. CVN
      did not bind well to the CVN-R and CVN-MR viruses. Propagating these viruses in
      cells treated with 1 mM deoxymannojirimycin (dMJ, mannosidase inhibitor)
      increased sensitivity to CVN, suggesting that glycans attached at other sites on
      HA1 that typically are not high-mannosidic became so due to dMJ treatment.
      Further evaluation showed that the Asp225Gly mutant virus was sensitive to the
      inhibitor and did not kill mice or induce weight loss. The CVN-R virus was also
      avirulent to mice. The double-mutant CVN-MR viruses were resistant to CVN and
      caused deaths and severe weight loss in mice. CVN-R virus subjected to mouse
      adaptation acquired the 225 mutation and a lethal phenotype. Thus, the 225
      mutation in the HA receptor-binding site in combination with a loss of glycan at
      Asn (63 or 94a) are important for mouse adaptation in this virus. The mutations
      reported here causing resistance to CVN are consistent with its known mode of
      action.

PMID- 18320937
TI  - Development of a population simulation model for HIV monotherapy virological
      outcomes using lamivudine.
AB  - Current highly active antiretroviral therapy (HAART) requires the use of
      combinations of three drugs to minimize the early emergence of drug-resistant HIV
      strains. Therefore, long-term monotherapy data with new agents are unavailable.
      However, the development of computer models for Monte-Carlo-type simulations of
      antiviral monotherapy, which incorporate HIV infection dynamic distributions from
      previously studied populations, together with pharmacokinetics and
      pharmacodynamic parameters of the new agent, could serve as an important tool.
      The nucleoside lamivudine (3TC) was used as a representative drug to standardize
      an improved pharmacodynamic and infection dynamic monotherapy model. 3TC plasma
      concentration versus time profiles was used to drive the cellular accumulation of
      3TC-triphosphate (TP) in primary human lymphocytes in the model, over a 16 week
      period. The fraction of HIV reverse transcription inhibited was calculated using
      the median inhibitory concentration and intracellular 3TC-TP levels. Virus loads
      and activated CD4+ T-cell counts were generated for 2,200 theoretical individuals
      and compared with the outcomes of an actual 3TC monotherapy trial at the same
      dose. Pharmacokinetic variance alone did not account for the interindividual HIV
      load variability. However, selection of appropriate distributions of the various
      pharmacokinetic and infection dynamics parameters produced a similar range of
      virus load reductions to actual observations. Therefore, once parameter and
      variance distributions are standardized, this modelling approach could be helpful
      in planning clinical trials and predicting the antiviral contribution of each
      agent in a HAART modality.

PMID- 18320939
TI  - [Epiglottitis: a children's disease seen in adults].
AB  - Two women, aged 58 and 62, developed epiglottitis with acute symptoms of sore
      throat, respiratory distress, fever, and stridor on inhalation. Both developed an
      upper respiratory tract obstruction requiring acute intubation to secure an open
      airway. The symptoms disappeared after administration of intravenous antibiotics
      and corticosteroids. Both women were discharged without any residual signs of
      infection. The incidence of epiglottitis in adults is most likely rising. The
      illness used to be seen almost only in children. A clear explanation for this
      rise in incidence cannot be given. It is important that the clinical picture be
      recognized in an early stage by referring doctors; they must be aware of the
      danger of a quickly developing airway obstruction. Monitoring of the patient
      during treatment by an otorhinolaryngologist is highly important to safeguard an
      adequate airway.

PMID- 18320938
TI  - Short communication cellular pharmacology of 9-(beta-D-1,3-dioxolan-4-yl) guanine
      and its lack of drug interactions with zidovudine in primary human lymphocytes.
AB  - Amdoxovir, currently in Phase II clinical trials, is rapidly converted to 9-(beta
      D-1,3-dioxolan-4-yl)guanine (DXG) by adenosine deaminase in vitro and in humans.
      The cellular pharmacology of DXG in primary human lymphocytes, including dose
      response relationships, intracellular half-life of DXG triphosphate (DXG-TP), and
      combination studies were determined. DXG produced high levels of DXG-TP with a
      long half-life (16 h) in activated human peripheral blood mononuclear cells.
      Since zidovudine (ZDV) and DXG select for different resistance mutations, co
      formulation of the these two drugs is an attractive proposition. A combination
      study between DXG and ZDV showed no reduction of DXG-TP or ZDV-TP. Taken
      together, these results suggest that an appropriately designed DXG prodrug could
      be given once a day and that co-formulation with ZDV might be a possibility.

PMID- 18320940
TI  - [The reporting of observational studies: useful and appreciable recommendations
      for improvement].
AB  - Much biomedical research is observational. Research should be reported in a way
      that enables the reader to comprehend the original objectives of the researchers,
      their subsequent actions and findings, and conclusions. A group of researchers,
      collaborating in the initiative 'Strengthening the reporting of observational
      studies in epidemiology' (STROBE), has recently drawn up recommendations
      regarding the preferable content of an accurate and complete report on an
      observational study. These 22 recommendations are summarised here with a
      commentary. These recommendations concern the title, the abstract, the
      introduction, the description of the methods and the results, the discussion and
      a list of the financiers of the study.

PMID- 18320941
TI  - [Fortification of food with folic acid diminishes the number of neural tube
      defects].
AB  - A recent study from a research group from Quebec showed a strong decrease in the
      number of births affected by a neural tube defect since folic acid fortification
      was introduced in Canada. The prevalence decreased from 1.58 neural tube defects
      per 1000 births before the introduction of folic acid fortification to 0.86 per
      1000 births in the period of complete fortification. Although folic acid
      fortification of staple food is probably the most effective way to decrease the
      incidence of neural tube defects, more knowledge about possible health risks
      should be obtained before fortification is introduced. More research is needed to
      determine which population groups are at risk of possible negative effects of
      folic acid fortification and at which level of fortification. Until then, it is
      important to generate more attention and publicity in order to increase awareness
      and knowledge concerning folic acid and to promote its use before and after
      conception.

PMID- 18320942
TI  - [New developments in the treatment of muscle-invasive bladder cancer].
AB  - Muscle-invasive bladder cancer is an important oncological problem. When no
      distant metastases are detected, a radical cystectomy is the standard treatment.
      In recent years new developments in the treatment of the disease have been
      explored. These developments comprise new surgical techniques such as neobladder
      construction using the patient's intestinal tissue, sexuality-preserving surgery
      and robot-assisted surgery. Furthermore, indications for perioperative
      chemotherapy are discussed. Finally, bladder-sparing approaches are described:
      brachytherapy and chemo-radiation.

PMID- 18320943
TI  - [Pedometers for monitoring and improvement of the level of physical activity].
AB  - Pedometers are cheap and easy to handle devices that have proven their accuracy
      to measure the number of steps taken during a time period (day or week). However,
      at lower walking speeds and if used by obese persons the accuracy of several
      pedometers decreases significantly. Pedometers are not able to record the
      intensity of daily physical activity. In addition, the number of steps depends on
      age, gender, body weight and season. Nevertheless, monitoring of daily physical
      activity with a pedometer may be an effective method to enhance the daily
      physical activity of selected subgroups. For instance, subjects with an increased
      risk of obesity or hypertension, sedentary patients with diabetes mellitus type
      2, patients with coronary heart disease and cancer patients can more easily be
      stimulated to become physically active and meet healthy living standards.
      Pedometers combined with existing effective counseling methods may be an
      effective strategy for many health care providers for adoption and enhancement of
      healthy lifestyles by sedentary patients.

PMID- 18320944
TI  - [How calcification in the atherosclerotic aorta can be associated with both a
      lower risk of recurrent stroke in clinical studies and an increased number of
      strokes in an autopsy study: interpretation based on selection bias].
AB  - Studies evaluating the role ofcalcification in the relationship between aortic
      atherosclerosis and stroke have led to contradictory conclusions: clinical
      studies show that aortic calcification is linked to a reduced risk of recurrence
      in stroke patients, while an autopsy series found a positive association between
      aortic calcification and stroke. The controversy can be explained by assuming
      that the risk associated with aortic atherosclerosis varies among individuals.
      Low-risk patients would live longer and have more time to develop calcification.
      Consequently, calcification would be a sign of low risk. This explains the
      apparent recurrence-reducing effect of calcification in stroke patients. The
      association between aortic calcification and stroke found in an autopsy series
      does not contradict this hypothesis but supports it: application of Berkson's
      fallacy shows that calcification is linked to lower mortality.

PMID- 18320945
TI  - [Diagnostic image (358). A neonate with splenomegaly and calcified adrenal
      glands].
AB  - A 10-day-old male neonate with feeding problems and splenomegaly had bilateral
      adrenal calcifications on plain abdominal X-ray caused by Wolman disease.

PMID- 18320946
TI  - [How many steps does a doctor take in the hospital? No difference between
      internists and general surgeons, but a relationship with age and BMI].
AB  - OBJECTIVE: To determine the number of steps taken during working days in the
      hospital by both internists and general surgeons and whether there is a
      difference between housemen, registrars and members of the staff. DESIGN:
      Comparative analysis. METHOD: A validated pedometer was used to count the number
      of steps taken by housemen, registrars and staff members in the departments of
      internal medicine and general surgery. The 2 groups of doctors comprised 131
      subjects from 13 training hospitals. Possible factors likely to affect the number
      of steps, such as age, sex, weight and height, were recorded. RESULTS: The
      average number of steps taken per day was 5325 (range: 1105-10,250) and the
      average number per hour was 548 (range: 143-1105), with an average working day of
      9.8 hours and 8.4 measured days. When corrected for age, sex and hierarchic
      status, no significant difference was observed between surgeons and internists (p
      = 0.097). There were also no differences within the hierarchic structure after
      correction (p = 0.936). Age and BMI seemed to be the most important factors
      predicting the number of steps in this population. Each additional year of age
      corresponded with an average decrease of 5 steps per hour on the job (p = 0.001),
      while each point rise in BMI (+1 kg/m) coincided with an average decrease of 20
      steps per hour (p = 0.001). CONCLUSION: After correcting for confounding factors,
      no differences were observed in the number of steps taken in the hospital by
      general surgeons and internists. There was also no difference between hierarchic
      levels. Age and BMI were the most important variables that predicted the number
      of steps taken per hour in this research population.

PMID- 18320947
TI  - [Neurological defects and developmental disorders following neonatal
      extracorporeal membrane oxygenation: results of a follow-up study after 5 years].
AB  - OBJECTIVE: Descriptive study of the development of children 5 years after
      neonatal extracorporeal membrane oxygenation (ECMO). DESIGN: Descriptive. METHOD:
      98 treated children were subjected to a paediatric, neurological, psychological,
      physiotherapeutic and logopaedic examination. The children came from 2 Dutch ECMO
      centres (the Erasmus MC-Sophia Children's Hospital in Rotterdam and the
      University Medical Centre St Radboud in Nijmegen, The Netherlands). RESULTS:
      Neurological disorders were found in 17 of the 98 investigated children, and in 6
      cases these were serious. Among the remaining 92 children, 24 had motor disorders
      and 11 had delayed cognitive development. The average IQ (100.5) was within the
      normal range. CONCLUSION: A significant proportion ofthe children that had been
      treated with ECMO had long-term morbidity in the form of neurological defects and
      developmental disorders.

PMID- 18320948
TI  - [Sigmoid carcinoma as a long-term complication following ureterosigmoidostomy].
AB  - A 45-year-old woman, known to have a congenital exstrophy ofthe bladder, for
      which she underwent a ureterosigmoidostomy in her infancy, presented with fever.
      This was due to pyelonephritis, from which she recovered with antibiotic therapy.
      During colonoscopy a carcinoma of the sigmoid was found at the level of the
      anastomosis of the ureters. Patients with a ureterosigmoidostomy have a one
      hundred-fold increased risk of colon carcinoma compared to the general
      population. The development of malignant tumours as a long-term complication of
      this procedure is linked with the frequent contact between intestinal tissue and
      urine. Periodical colonoscopy of these patients is advised.

PMID- 18320949
TI  - [A giant pseudocyst following repair of an incisional hernia by a propylene
      mesh].
AB  - A 79-year-old woman presented with a huge, asymptomatic, balloon-like abdomen,
      which gradually developed after polypropylene mesh repair of an incisional hernia
      following a median laparotomy. Additional CT showed a huge cyst measuring 20 x 24
      cm which seemed to originate from the anterior abdominal wall and lacked
      communication with the inner abdominal space. Subsequently an explorative
      laparotomy was performed. The content of the cyst consisted of dark brown
      serosanguineous material. The inferior portion was firmly affixed to the mesh.
      The entire cyst, except for the part fixed to the mesh, was excised followed by
      an abdominoplasty. Histological examination showed aspecific signs of
      inflammation due to a foreign body, and haemorrhagic material without epithelial
      lining. The diagnosis 'giant pseudocyst' was established. Etiologically, this
      condition is probably related to postoperative formation of a seroma, which is a
      well-known complication after mesh repair, especially when a polypropylene mesh
      is used. Postoperative formation of a haematoma might be a causative factor as
      well. Former literature reports 11 cases of such giant cyst formation after mesh
      repair ofhernias. In one study a prevalence of 0.45% is mentioned. This
      complication may be an underreported phenomenon.

PMID- 18320950
TI  - [Keeping up to date with the relevant literature: 'really simple syndication'
      (RSS)-feeds within PubMed].
AB  - For clinicians, researchers and policy makers in healthcare, it is important to
      keep up to date with the newest medical-scientific information. The large amount
      of new information makes this a difficult task. There are various techniques for
      keeping up to date, for instance reading systematic reviews, searching the
      literature at regular intervals oneself, and using the e-mail alerting services
      of, for example, PubMed. A new possibility is to be alerted to new scientific
      publications, for example, via a 'really simple syndication' (RSS)-feed. This
      option is now also made available by PubMed. In addition to PubMed, many other
      websites can now be searched systematically for new information by a RSS reader.
      With RSS feeds the user can be alerted to new information much faster than by an
      e-mail alerting service, so that one can anticipate new developments more
      rapidly.

PMID- 18320951
TI  - [Diagnostic and prognostic value of B-type natriuretic peptides in heart failure
      or signs of heart failure].

PMID- 18320952
TI  - [Arthralgia and urticaria as immune-complex mediated complications after
      meningitis with meningococci group B].

PMID- 18320953
TI  - [Diagnostic image (339). A woman with jerking legs].

PMID- 18320954
TI  - Quality care, patient safety, and the focus on technology.

PMID- 18320955
TI  - Should I take this course online?
AB  - As the number of online nursing courses increases, students are faced with the
      daunting question, "Should I take this course online?" Although online courses
      are convenient, convenience should not be the sole factor for making this
      decision. Students and their advisors should discuss the characteristics of
      successful online students before deciding to take a course online. A study was
      conducted in which the same face-to-face and online version of a course were
      compared using Ragan's framework. The results of the study describe
      characteristics that can serve as useful criteria for predicting student success
      in an online course.

PMID- 18320956
TI  - Challenging stereotyping and bias: a voice simulation study.
AB  - Stigma is a barrier to mental health care access for patients with schizophrenia
      and can interfere with developing therapeutic relationships. This study
      demonstrates success of a voice simulation experience during orientation in
      changing the biases of nursing students and the effect on the development of the
      nurse-patient relationship. Ninety-four individuals participated; 52 received a
      voice simulation experience during orientation, and 42 received orientation with
      no voice simulation experience. The Medical Condition Regard Scale was
      administered before and after orientation. Posttest paired t test results show
      significant differences in attitudes toward patients with voice hearing
      experiences between the two groups. The themes of personal growth from the focus
      groups postorientation include Affective Experience, Physical Experience, and
      Empathy. Findings demonstrate that the orientation process should include methods
      to challenge stereotyping and bias to decrease stigma, improve service access,
      and enhance the ability to develop therapeutic relationships.

PMID- 18320957
TI  - Developmental disabilities: improving competence in care using virtual patients.
AB  - Nurse practitioners (NPs) have an increasingly important role in health care
      provision in the United States. However, most nurses report that they receive
      little or no clinical training in the area of developmental disabilities. A core
      development team consisting of NP faculty members from three universities, one
      physician assistant faculty member, the parents of children with developmental
      disabilities, and educational specialists developed two multimedia interactive
      pediatric instructional modules in CD-ROM format: one involving a child with Down
      syndrome and the other, an infant born at 26 weeks gestation. Participants were
      required to make decisions about proper clinical interaction throughout the
      cases. The modules on CD were piloted with NP students at three universities.
      Effectiveness study results demonstrated significant gains in both knowledge and
      comfort level regarding the care of patients with developmental disabilities.

PMID- 18320958
TI  - Handheld computers in nursing education: PDA pilot project.
AB  - Interest in the use and application of handheld technology at undergraduate and
      graduate nursing programs across the country is growing rapidly. Personal digital
      assistants (PDAs) are often referred to as a "peripheral brain" because they can
      save time, decrease errors, and simplify information retrieval at the point of
      care. In addition, research results support the notion that PDAs enhance nursing
      clinical education and are an effective student learning resource. However, most
      nursing programs lack the full range of technological resources to implement and
      provide ongoing support for handheld technology use by faculty and students. This
      article describes a 9-month pilot project for the initial use of PDAs by novice
      faculty and students at Simmons College.

PMID- 18320959
TI  - Videoconferencing and Web-based conferencing to enhance learning communities.
AB  - Preparing nursing students to develop the leadership and management skills
      necessary to adapt to ever-changing practice environments is a challenge for
      educators. Videoconferencing and Web-based conferencing allow for expansion of
      traditional classroom walls to develop partnerships among peers, exchange
      perspectives, and gain a more global understanding of nursing care delivery
      systems. A collaborative leadership seminar using videoconferencing was used to
      connect two large colleges of nursing in the midwestern United States, and
      through Web-based conferencing, one of the midwestern colleges was connected to a
      university in the United Kingdom. Objectives for students were exposure to
      different schools of thought, management of care via technology, network and
      cultivation of global perspectives on health care delivery, and experience of
      novel educational approaches.

PMID- 18320960
TI  - Applying the Principles of Significant Learning in the e-learning environment.
AB  - E-learning technologies in education use adult learning theories that view the
      educator as a facilitator of learning and an assessor of outcomes. The change to
      this technology requires a shift in the focus of a course from the educator to
      the subject. The experience of one faculty member involved in an implementation
      of an online program is used to demonstrate the application of Fink's principles
      of significant learning in the virtual environment. Fink urged faculty to create
      learning-centered courses, as opposed to content-centered courses. The taxonomy
      of six course components he proposed as necessary to significant learning are
      foundational knowledge, application, integration, human dimension, caring, and
      learning how to learn. Fink's taxonomy of significant learning can be used as a
      framework to focus course planning and assessment of student outcomes as courses
      are adapted to a Web-based environment.

PMID- 18320961
TI  - Using interactive video technology in nursing education: a pilot study.
AB  - A pilot study was conducted to analyze the benefits of using interactive
      technology with external assessors and graduating senior nursing students during
      Senior Nurse Leadership Assessment Day at the University of Central Missouri. The
      primary aim was to determine whether videoconferencing technology would promote
      recruitment and retention of professional nurse external assessors without
      compromising student learning. Among the issues discussed are the advantages and
      disadvantages of using interactive videoconferencing technology in education and
      the influence of external assessors in nursing education. The study results
      indicate that interactive videoconferencing is an effective, accepted format for
      educational opportunities such as Senior Nurse Leadership Assessment Day, based
      on the lived experiences of the study participants. In addition, the results
      demonstrate that interactive videoconferencing does not compromise student
      learning or assessment by external assessors.

PMID- 18320962
TI  - "Learning it forward": creating an assignment for emergency preparedness.

PMID- 18320963
TI  - 2008 legislative session preview.

PMID- 18320964
TI  - Tort reform: worth fighting for a view from the trenches.

PMID- 18320965
TI  - Reaping the benefits of tort reform: good medicine for Georgians.

PMID- 18320966
TI  - Will older doctors opt out of medicine?

PMID- 18320967
TI  - Medicine and adventure in Sikkim: in the spirit of Tenzing and Mallory.

PMID- 18320968
TI  - The experience of others is often the best teacher.

PMID- 18320969
TI  - Hall County's Health Access Initiative: linking those in need to specialty care.

PMID- 18320970
TI  - Hope for the hopeless: Georgia's largest free clinic.

PMID- 18320971
TI  - MRSA in health care settings.

PMID- 18320972
TI  - Significant changes to Stark rules of significant interest to physicians.

PMID- 18320973
TI  - Veterinarians and animal welfare--a comment.

PMID- 18320974
TI  - An ethicist's commentary on the raw milk case.

PMID- 18320975
TI  - Annual veterinary productivity in companion animal practice in the different
      provinces.

PMID- 18320976
TI  - An investigation of the presence of Escherichia coli O149:K91:F4 on pig farms in
      southern Ontario and the use of antimicrobials and risk factors associated with
      the presence of this serogroup.
AB  - Prevalence, causative factors, treatment, and preventative measures for
      O149:K91:F4 Escherichia coli infection of postweaning pigs was determined by
      using a cross-sectional study including 70 farms in Ontario. Surveys were
      distributed and samples cultured bacteriologically, resulting in 30% of farms
      testing positive to E. coli 0149:K91:F4. Possible causative factors, such as
      housing or nutrition, were not significantly different between positive and
      negative farms. Use of injectable antibiotics (P = 0.05) and zinc oxide (P =
      0.003) was higher on E. coli O149:K91:K88 (F4)-positive farms. A higher level of
      biosecurity and the presence of other diseases may be associated with an
      increased risk of isolating E. coli O149:K91:F4 from weanling pigs.

PMID- 18320977
TI  - Comparative evaluation of the liver in dogs with a splenic mass by using
      ultrasonography and contrast-enhanced computed tomography.
AB  - Evaluation of dogs with splenic masses to better educate owners as to the extent
      of the disease is a goal of many research studies. We compared the use of
      ultrasonography (US) and contrast-enhanced computed tomography (CT) to evaluate
      the accuracy of detecting hepatic neoplasia in dogs with splenic masses,
      independently, in series, or in parallel. No significant difference was found
      between US and CT. If the presence or absence of ascites, as detected with US,
      was used as a pretest probability of disease in our population, the positive
      predictive value increased to 94% if the tests were run in series, and the
      negative predictive value increased to 95% if the tests were run in parallel. The
      study showed that CT combined with US could be a valuable tool in evaluation of
      dogs with splenic masses.

PMID- 18320978
TI  - Transtracheal aspiration in the diagnosis of pulmonary blastomycosis (17 cases:
      2000-2005).
AB  - Blastomyces dermatitidis is a common etiologic agent of fungal pneumonia in dogs.
      Definitive diagnosis is based on cytologic demonstration of the organism in
      affected tissues. Fluid obtained through transtracheal aspiration has previously
      been reported to have a low diagnostic yield for B. dermatitidis organisms. This
      retrospective study identified B. dermatitidis organisms in 76% of samples when
      transtracheal aspiration was performed in 17 nonsedated dogs with pulmonary
      blastomycosis. Transtracheal aspiration is a noninvasive and simple procedure
      that should be considered as an early diagnostic test whenever blastomycosis is a
      differential diagnosis in dogs with pulmonary disease.

PMID- 18320979
TI  - The persistence of benzimidazole-resistant cyathostomes on horse farms in Ontario
      over 10 years and the effectiveness of ivermectin and moxidectin against these
      resistant strains.
AB  - Three clinical trials with fecal egg count reduction tests and coproculture were
      conducted on 2 standardbred farms in Ontario. On Farm A, the treatment groups
      were mebendazole and ivermectin in trial 1, and fenbendazole and moxidectin in
      another. On Farm B, treatment groups were mebendazole and ivermectin. All horses
      treated with mebendazole or fenbendazole were subsequently treated with
      ivermectin or moxidectin. Strongyle eggs/g feces were estimated pre- and post
      treatment using the Cornell-McMaster dilution and Cornell-Wisconsin centrifugal
      flotation techniques. After treatment, there was no change in the arithmetic mean
      eggs/g feces for horses given mebendazole, and a reduction of only 49.1% for
      those given fenbendazole. All horses receiving ivermectin or moxidectin had their
      egg counts reduced to 0. Only cyathostomes were found on culture. On both farms
      the benzimidazole resistant strains appeared to have persisted for at least 10
      years. Development of and monitoring for anthelmintic resistance are briefly
      discussed.

PMID- 18320980
TI  - Fibrous vaginal hamartoma in a newborn calf.
AB  - A 2-day-old female Holstein calf was presented for abnormal structures protruding
      from the vulva at birth. A diagnosis of fibrous vaginal hamartoma was made, based
      on macroscopic and histologic examinations of the abnormal tissue. Management of
      this case involved surgical mass ablation.

PMID- 18320981
TI  - Hemodialysis in a dog with acute renal failure from currant toxicity.
AB  - A 3 1/2-year-old Labrador retriever being presented for acute onset vomiting and
      lethargy was diagnosed with acute renal failure (ARF). The dog had ingested dried
      currants, a type of raisin. Hemodialysis was successfully performed to treat the
      ARE Raisin toxicity can cause ARF and warrants early recognition and aggressive
      treatment.

PMID- 18320982
TI  - A retrospective study of canine persistent nasal disease: 80 cases (1998-2003).
AB  - Persistent canine nasal disease is a common complaint in small animal practice;
      however, an etiologic diagnosis can be difficult to establish. The aim of this
      retrospective study was to determine the percentage of cases for which the
      etiology was determined in our hospital population. Medical records from 80 dogs
      met the criteria of inclusion in the study. Nonspecific rhinitis was identified
      in 23.7% of cases. Other diagnoses were neoplasia (15.0%), fungal infection
      (nasal aspergillosis) (8.7%), cleft palate (8.7%), periodontal disease (4.0%),
      parasites (1.3%), foreign body (1.3%), and primary bacterial disease (1.3%). A
      definitive diagnosis could not be established in 36.3% of cases. Dogs with
      neoplastic and mycotic diseases often presented with severe radiographic and
      rhinoscopic lesions. Despite a systematic approach, numerous cases went
      undiagnosed. The use of advanced imaging should increase our ability to obtain an
      etiologic diagnosis in canine nasal disease.

PMID- 18320983
TI  - Ultrasound-guided fine needle aspiration in the diagnosis of peripheral nerve
      sheath tumors in 4 dogs.
AB  - Ultrasound-guided fine needle aspiration was used in establishing the diagnosis
      in 4 cases of malignant peripheral nerve sheath tumor. Sonographic and cytologic
      characteristics are discussed. Because of its availability and ease of use,
      axillary ultrasonography with fine needle aspiration can be an initial diagnostic
      step for suspected brachial plexus tumors.

PMID- 18320984
TI  - Palliative therapy of osteochondrosis dessicans in a Duroc boar.
AB  - A 2-year-old, 210-kg, Duroc boar manifested with a grade II-III left front
      lameness. The boar was treated systemically with isolfupredone acetate and a 5
      week course of ketoprofen. The lameness resolved and the ketoprofen was
      discontinued; however, the lameness returned and the boar was euthanized
      humanely. Postmortem examination was consistent with osteochondrosis dessicans.

PMID- 18320985
TI  - Idiopathic vesicular disease in swine in Manitoba.

PMID- 18320986
TI  - The CALAM/ACMAL standards of veterinary care and laboratory animal welfare.

PMID- 18320987
TI  - What are your clinical diagnosis, differential diagnoses, therapeutic plan, and
      prognosis? Diffuse episcleritis of the right eye.

PMID- 18320988
TI  - When family members disagree.

PMID- 18320989
TI  - Beyond Schiavo.

PMID- 18320990
TI  - Commentary on "Beyond Schiavo": beyond theory.

PMID- 18320991
TI  - A commentary on Caplan and Bergman: ethics mediation--questions for the future.

PMID- 18320992
TI  - Mediation and moral aporia.

PMID- 18320993
TI  - Hope, uncertainty, and lacking mechanisms.

PMID- 18320994
TI  - How much emotion is enough?

PMID- 18320995
TI  - Real life informs consent.

PMID- 18320996
TI  - What parents face with their child's life-threatening illness: comment on "How
      much emotion is enough?" and "Real life informs consent".

PMID- 18320997
TI  - Reflections on love, fear, and specializing in the impossible.

PMID- 18320998
TI  - Emotion, suffering, and hope: commentary on "How much emotion is enough"?

PMID- 18320999
TI  - Let's value, but not idealize, emotions.

PMID- 18321000
TI  - Jewish law and end-of-life decision making: a case report.

PMID- 18321001
TI  - When surrogates' responsibilities and religious concerns intersect.

PMID- 18321002
TI  - A tale of two daughters: Jewish law and end-of-life decision making.

PMID- 18321003
TI  - The case of Mr. A.B.

PMID- 18321010
TI  - Perceptions of sexual consent: the impact of relationship history and gender.
AB  - The current study examined how situational (i.e., couple-specific relationship
      experience) and participant (i.e., gender) factors influence attributions about
      sexual consent. Four hundred and fourteen undergraduates were randomly assigned
      to read one of three vignettes in which consent for sexual intercourse was
      ambiguous. Within the three conditions the couple's relationship history was
      manipulated. A 2 x 3 between subjects multivariate analysis of variance revealed
      that, as the degree of intimacy between the couple increased, perceptions of
      consent, acceptability, and clarity increased. A main effect for participant
      gender also was found. Men, more than women, perceived the scenarios as more
      consensual, acceptable, and clear regardless of relationship experience. No
      interaction was found. These findings are discussed in light of sexual precedence
      and sexual scripts.

PMID- 18321011
TI  - Adolescents' sexual scripts: schematic representations of consensual and
      nonconsensual heterosexual interactions.
AB  - The characteristic features of adolescents' sexual scripts were explored in 400
      tenth and eleventh graders from Berlin, Germany. Participants rated the
      prototypical elements of three scripts for heterosexual interactions: (1) the
      prototypical script for the first consensual sexual intercourse with a new
      partner as pertaining to adolescents in general (general script); (2) the
      prototypical script for the first consensual sexual intercourse with a new
      partner as pertaining to themselves personally (individual script); and (3) the
      script for a nonconsensual sexual intercourse (rape script). Compared with the
      general script for the age group as a whole, the individual script contained
      fewer risk elements related to sexual aggression and portrayed more positive
      consequences of the sexual interaction. Few gender differences were found, and
      coital experience did not affect sexual scripts. The rape script was found to be
      close to the "real rape stereotype." The findings are discussed with respect to
      the role of sexual scripts as guidelines for behavior, particularly in terms of
      their significance for the prediction of sexual aggression.

PMID- 18321012
TI  - Time period and lesbian identity events: a comparison of Norwegian lesbians
      across 1986 and 2005.
AB  - The purpose of the present work was to investigate the assumption that the lives
      of lesbians are easier today. When exploring the hypothesis that identity events
      (e.g., coming out to parents) among lesbian women have changed over time and
      happen earlier in life today, we expected to find several time period effects.
      Two national samples obtained through mailed questionnaires were compared, 1986
      (n = 123) and 2005 (n = 236), age range 20-49. Time period effects were found,
      including informants reporting identifying as lesbian earlier in life. Time
      period effects, however, were not found regarding relational identity events such
      as informing others about one's identity status. The findings did not reveal any
      conclusive evidence that it is easier to establish a lesbian lifestyle today.

PMID- 18321013
TI  - Predicting perceptions of sexual harassment based on type of resistance and
      belief in token resistance.
AB  - This study examined perceptions of sexual harassment based on belief in women's
      use of token resistance and a victim's physical or verbal resistance to unwanted
      sexual attention, described in experimentally manipulated vignettes. Findings
      from 541 undergraduates revealed that a stronger belief in token resistance was
      associated with weaker perceptions of sexual harassment. Results showed that any
      type of resistance led to stronger perceptions of sexual harassment than no
      resistance at all, except for those with a stronger belief in women's use of
      token resistance. Perceptions among those with a stronger belief strengthened
      only when there were two forms of resistance offered simultaneously. These
      findings extend the literature by investigating the influence of physical
      resistance on sexual harassment perceptions.

PMID- 18321014
TI  - Turning sexual science into news: sex research and the media.
AB  - In this article we report on the findings of a two-part project investigating
      contemporary issues in sexuality researchers' interaction with journalists. The
      goal of the project was to explore best practices and suggest curricular and
      training initiatives for sexuality researchers and journalists that would enhance
      the accurate dissemination of sexuality research results in the media. We present
      the results of a survey of a convenience sample of 94 sexuality researchers about
      their experiences and concerns regarding media coverage and a summary of the main
      themes that emerged from an invitational conference of sexuality researchers and
      journalists. In addition, we present some preliminary recommendations for
      training and best practices. Topics assessed include reporting accuracy; sex
      researchers' comfort with various topics, media, and journalists; researchers'
      perceptions of the purpose and content of articles; concern about the impact of
      media coverage; and training for sexuality researchers.

PMID- 18321015
TI  - Genetic and environmental effects on sexual excitation and sexual inhibition in
      men.
AB  - The Sexual Inhibition and Sexual Excitation Scales (SIS/SES) measure the
      propensity for sexual inhibition and excitation in men. According to the
      theoretical model underlying the SIS/SES, sexual response and associated behavior
      depend on dual control mechanisms in the brain involving the balance of
      excitatory and inhibitory systems which impinge on sexual response. Previous
      research with the SIS/SES has indicated one higher-order excitatory factor and
      two higher-order inhibitory factors affecting sexual response. The present study
      analyzed the item structure and the psychometric properties of the instrument in
      a population based sample of Finnish male twins (N = 1,289), and, including 37
      out of 45 items of the original scales, estimated the heritability of and the
      environmental influences on the excitatory and inhibitory mechanisms. The twin
      correlations and the structural equation modeling suggested modest heritability
      for both inhibitory mechanisms. Sexual excitation, in contrast, was not
      influenced by genetic effects and similarities between twins for this mechanism
      seemed to be caused by the common environment of the twins.

PMID- 18321016
TI  - The gender identity/gender dysphoria questionnaire for adolescents and adults.
AB  - The present study reports on the construction of a dimensional measure of gender
      identity (gender dysphoria) for adolescents and adults. The 27-item gender
      identity/gender dysphoria questionnaire for adolescents and adults (GIDYQ-AA) was
      administered to 389 university students (heterosexual and nonheterosexual) and 73
      clinic-referred patients with gender identity disorder. Principal axis factor
      analysis indicated that a one-factor solution, accounting for 61.3% of the total
      variance, best fits the data. Factor loadings were all >or= .30 (median, .82;
      range, .34-.96). A mean total score (Cronbach's alpha, .97) was computed, which
      showed strong evidence for discriminant validity in that the gender identity
      patients had significantly more gender dysphoria than both the heterosexual and
      nonheterosexual university students. Using a cut-point of 3.00, we found the
      sensitivity was 90.4% for the gender identity patients and specificity was 99.7%
      for the controls. The utility of the GIDYQ-AA is discussed.

PMID- 18321017
TI  - Longitudinal test of a multiple domain model of adolescent condom use.
AB  - A comprehensive multiple domain model (MDM) to understand condom use in
      adolescents was proposed and tested using structural equation modeling of data at
      three time points. The proposed model integrates social psychological theory,
      demographic and personality factors, social environment, and
      situational/contextual variables. Adolescents who were sexually active at time 2
      (6 months after baseline) and time 3 (1 year after time 2) and completed surveys
      at all three time points were included in the analyses (N = 511). An iterative
      process of model testing resulted in a structural equation model that provided a
      good fit to the data (CFI = .92, RMSEA = .04). Models comparing gender and race
      as moderators also were calculated and supported the generalizability of the
      model. Results provide support for an MDM that goes beyond traditional social
      psychological models for a broader understanding of condom use in adolescents.
      Implications for further theory testing and safer sexual interventions are
      discussed.

PMID- 18321024
TI  - In memory of Albert Ellis (1913-2007).

PMID- 18321025
TI  - In memory of Robert W. Hatfield, Ph.D.

PMID- 18321026
TI  - Sampling television programs for content analysis of sex on TV: how many episodes
      are enough?
AB  - Content analysis is widely used to analyze sexual themes and messages on
      television. Although researchers generally use a sampling procedure to identify
      programs for analysis, there is currently no gold standard for the number of
      episodes needed to establish a valid, representative sample. This study sought to
      explore how many episodes of weekly television programs should be examined for an
      accurate assessment of sexual content present throughout the season. Various
      sampling strategies were used to select episodes from programs that ran in the
      1998-1999 season, and results were compared with data collected from all episodes
      of these programs to test representativeness. Findings suggest that to provide a
      representative assessment of sexual content on television programs for behavior
      level variables, a random sample of five episodes of weekly television programs
      is sufficient, while three episodes may be acceptable if variation is minimal. A
      random sample of seven episodes is needed for character-based analyses.

PMID- 18321027
TI  - Perceptions of sources of sex education and targets of sex communication:
      sociodemographic and cohort effects.
AB  - As part of a larger survey study on young adult sexuality conducted over a 17
      year period at a Midwest U.S. university, more than 6,000 college students
      completed questions on the sources of their sex education and the degree to which
      they have communicated about sex with various types of individuals. Participants
      reported receiving more sex education from peers and media than from parents (and
      mothers more than fathers). Respondents also reported communicating more about
      sex with peers than with parents or any other categories of individuals.
      Differences were found in the degree of sex education from various sources and in
      communication with various targets based on gender, ethnic background, and social
      class. Furthermore, changes were found over the 17-year period. More recent
      cohorts of students perceived that they received more sex education from media,
      peers, and professionals, and communicated more about sex with professionals,
      relative to earlier cohorts.

PMID- 18321028
TI  - Sexual deception as a social-exchange process: development of a behavior-based
      sexual deception scale.
AB  - The use of deception in association with sexual encounters may take many forms,
      ranging from outright lies to more subtle, evasive manipulations. To address such
      deceptions, a behavior-based sexual deception scale was developed utilizing
      social exchange theory. Participants were 267 individuals associated with two
      large universities who were surveyed regarding different aspects of their sexual
      deceptive behaviors. In addition, items addressing sexually related behaviors and
      attitudes were assessed for validation purposes. Principal components analysis
      identified three components of sexual deception, labeled Blatant Lying, Self
      Serving, and Avoiding Confrontation. Confirmatory factor analysis verified the
      resulting structure, and promising validity was noted. In general, those using
      any of these deceptions reported more sexual partners and one-night stands. Those
      telling blatant lies to have sex were more likely to report greater needs for
      sex, while those using self-serving lies or having sex to avoid confrontation
      experienced greater worry about partner loss. Men were more likely to use blatant
      lies to have sex, while women were more likely to have sex to avoid
      confrontation. Results support sexual deception as an exchange process, with sex
      for pleasure and positive relationship outcomes acting as rewards, and unwanted
      sex and deception consequences as costs. Implications for health interventions
      and primary prevention applications are discussed.

PMID- 18321029
TI  - Women's scores on the sexual inhibition/sexual excitation scales (SIS/SES):
      gender similarities and differences.
AB  - The Sexual Inhibition/Sexual Excitation Scales (SIS/SES) assess individual
      propensities to become sexually aroused and to inhibit arousal. Prior analyses of
      men's SIS/SES data (Janssen, Vorst, Finn, & Bancroft, 2002a) yielded one
      excitation factor (SES) and two inhibitory factors (SIS1/Threat of Performance
      Failure and SIS2/Threat of Performance Consequences). The current study utilized
      a dataset of 2,045 undergraduates (1,067 women and 978 men) to examine the
      psychometric properties of women's SIS/SES scores. Women scored higher on sexual
      inhibition and lower on sexual excitation compared with men. The
      convergent/discriminant validity of women's SIS/SES scores globally resembled
      men's, but showed stronger associations with other sexuality - related measures
      and less pronounced relationships with measures of general behavioral
      approach/avoidance. The test-retest reliability of men's and women's SIS/SES
      scores were similar, but individual items exhibited differential relevance to
      men's and women's arousal. An exploratory factor analysis of women's scores was
      utilized to further examine shared and unshared themes.

PMID- 18321030
TI  - Body image, body satisfaction, and unsafe anal intercourse among men who have sex
      with men.
AB  - Using survey results from the 1998 Twin Cities Lesbian, Gay, Bisexual, and
      Transgender (LGBT) Pride Festival (N = 535), we explored associations between
      body image and unsafe anal intercourse (UAI) among men who have sex with men
      (MSM), and evaluated whether body satisfaction mediated this association. MSM who
      reported underweight body image had lower odds than those who reported average
      weight of UAI (AOR = 0.33; 95% CI = 0.13, 0.85); body satisfaction was not found
      to mediate this association. 13.3% of men who reported overweight/obese body
      image had engaged in UAI compared with 21.6% of those who reported average weight
      and 8.2% of those who reported underweight (p < .05). Compared with MSM in
      exclusive relationships, MSM in non exclusive relationships had increased odds of
      UAI (AOR = 5.78; 95% CI = 2.96, 11.29) as did men who were not partnered (AOR =
      3.20; 95% CI = 1.72, 5.93). These findings highlight the importance of including
      body image in sexual behavior models of MSM to better understand body image's
      role in influencing sexual risk and sexually transmitted infections (STI)/human
      immunodeficiency virus (HIV) transmission.

PMID- 18321031
TI  - Women's erotic rape fantasies: an evaluation of theory and research.
AB  - This article is the first systematic review of the research literature on women's
      rape fantasies. Current research indicates that between 31% and 57% of women have
      fantasies in which they are forced into sex against their will, and for 9% to 17%
      of women these are a frequent or favorite fantasy experience. Erotic rape
      fantasies are paradoxical: they do not appear to make sense. Why would a person
      have an erotic and pleasurable fantasy about an event that, in real life, would
      be abhorrent and traumatic? In this article, the major theories of women's rape
      fantasies are evaluated both rationally and empirically. These theories explain
      rape fantasies in terms of masochism, sexual blame avoidance, openness to
      sexuality, sexual desirability, male rape culture, biological predisposition to
      surrender, sympathetic physiological activation, and adversary transformation.
      This article evaluates theory and research, makes provisional judgments as to
      which theories appear to be most viable, and begins the task of theoretical
      integration to arrive at a more complete and internally consistent explanation
      for why many women engage in erotic rape fantasies. Methodological critiques and
      programs for future research are presented throughout.

PMID- 18321032
TI  - Latino sexual styles: developing a nuanced understanding of risk.
AB  - Theoreticians in adolescent sexuality have called for research that is
      contextual, health-focused, balanced between males and females, and from the
      perspective of adolescents, noting that scales developed by Buzwell and Rosenthal
      (1996) are promising. Cross-cultural validation of the measures in the United
      States. should include Latino adolescents, as they are the fastest-growing ethnic
      group. Contextual issues for this population include the roles of culture and the
      family, country of origin, and acculturation. The scales were tested with 155
      Latino adolescents, Mexican-identified, and third generation plus. Scales
      indicated good reliability overall although several subscales were determined to
      best be combined as they created a single factor. Hierarchical agglomerative
      methods revealed a four-cluster solution with clusters conceptually mapping the
      original study. Clusters were significantly different on important sexual
      behaviors, such as virginity status, likelihood of engaging in safer sex, and
      number of sex partners.

PMID- 18321036
TI  - Synthesis and biological effects of c(Lys-Lys-Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile
      Leu) (JMV2012), a new analogue of neurotensin that crosses the blood-brain
      barrier.
AB  - The central administration of neurotensin (NT) or of its C-terminal hexapeptide
      fragment NT(8-13), produces strong analgesic effects in tests evaluating acute
      pain. The use of NT-derived peptides as pharmaceutical agents to relief severe
      pain in patients could be of great interest. Unfortunately, peptides do not
      readily penetrate the blood-brain barrier. We have observed that the cyclic NT(8
      13) analogue, c(Lys-Lys-Pro-Tyr-Ile-Leu-Lys-Lys-Pro-Tyr-Ile-Leu) (JMV2012,
      compound 1), when peripherally administered to mice produced analgesic and
      hypothermic effects, suggesting the peptide penetrates the blood-brain barrier
      and functions effectively like a drug. Moreover, dimeric compounds show increased
      potency compared to their corresponding monomer. We present the synthesis of the
      cyclic dimer compound 1 (JMV2012). In mice, compound 1 induced a profound
      hypothermia and a potent analgesia, even when peripherally administered. Compound
      1 appears to be an ideal lead compound for the development of bioactive NT
      analogues as novel analgesics drugs.

PMID- 18321037
TI  - Structure-guided design of aminopyrimidine amides as potent, selective inhibitors
      of lymphocyte specific kinase: synthesis, structure-activity relationships, and
      inhibition of in vivo T cell activation.
AB  - The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic
      tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic
      evidence, including knockout mice and human mutations, demonstrates that Lck
      kinase activity is critical for normal T cell development, activation, and
      signaling. Selective inhibition of Lck is expected to offer a new therapy for the
      treatment of T-cell-mediated autoimmune and inflammatory disease. With the aid of
      X-ray structure-based analysis, aminopyrimidine amides 2 and 3 were designed from
      aminoquinazolines 1, which had previously been demonstrated to exhibit potent
      inhibition of Lck and T cell proliferation. In this report, we describe the
      synthesis and structure-activity relationships of a series of novel
      aminopyrimidine amides 3 possessing improved cellular potency and selectivity
      profiles relative to their aminoquinazoline predecessors 1. Orally bioavailable
      compound 13b inhibited the anti-CD3-induced production of interleukin-2 (IL-2) in
      mice in a dose-dependent manner (ED 50 = 9.4 mg/kg).

PMID- 18321038
TI  - Probing distal regions of the A2B adenosine receptor by quantitative structure
      activity relationship modeling of known and novel agonists.
AB  - The binding modes at the A 2B adenosine receptor (AR) of 72 derivatives of
      adenosine and its 5'- N-methyluronamide with diverse substitutions at the 2 and N
      (6) positions were studied using a molecular modeling approach. The compounds in
      their receptor-docked conformations were used to build CoMFA and CoMSIA
      quantitative structure-activity relationship models. Various parameters,
      including different types of atomic charges, were examined. The best statistical
      parameters were obtained with a joint CoMFA and CoMSIA model: R (2) = 0.960, Q
      (2) = 0.676, SEE = 0.175, F = 158, and R (2) test = 0.782 for an independent test
      set containing 18 compounds. On the basis of the modeling results, four novel
      adenosine analogues, having elongated or bulky substitutions at N (6) position
      and/or 2 position, were synthesized and evaluated biologically. All of the
      proposed compounds were potent, full agonists at the A 2B AR in adenylate cyclase
      studies. Thus, in support of the modeling, bulky substitutions at both positions
      did not prevent A 2B AR activation, which predicts separate regions for docking
      of these moieties.

PMID- 18321039
TI  - Discovery of a novel A2B adenosine receptor antagonist as a clinical candidate
      for chronic inflammatory airway diseases.
AB  - Recently, we have reported a series of new 1,3-symmetrically (R 1 = R 3)
      substituted xanthines ( 3 and 4) which have high affinity and selectivity for the
      human adenosine A 2B receptors (hA(2B)-AdoR). Unfortunately, this class of
      compounds had poor pharmacokinetic properties. This prompted us to investigate
      the effect of differential alkyl substitution at the N-1 and N-3 positions ( N 1
      R not equal to N 3-R) on A(2B)-AdoR affinity and selectivity; we had the dual
      objectives of enhancing affinity and selectivity for the A(2B)-AdoR, as well as
      improving oral bioavailability. This effort has led to the discovery of compound
      62, that displayed high affinity and selectivity for the hA(2B)-AdoR (K(i) = 22
      nM). In addition, compound 62 showed high functional potency in inhibiting the
      accumulation of cyclic adenosine monophosphate induced by 5'- N
      ethylcarboxamidoadenosine in HEK-A(2B)-AdoR and NIH3T3 cells with K(B) values of
      6 and 2 nM, respectively. In a single ascending-dose phase I clinical study,
      compound 62 had no serious adverse events and was well tolerated.

PMID- 18321040
TI  - Stereocontrol by a pair of epimeric sugar-derived ligands of the coordination
      sphere of copper(II) complexes.
AB  - A pair of novel C3-epimeric sugar-derived ligands (glycoligands) with a neutral
      N4O donor set was synthesized. Copper(II) complexes of both ligands were obtained
      and characterized by X-ray crystallography. Cyclic voltammetry, electron
      paramagnetic resonance, and UV-vis spectroscopies showed similar electronic
      properties. Mirror-image CD spectra were obtained for the Cu(II) d-d band,
      indicating an enantiomeric character of the coordination sphere, which has been
      rationalized structurally. This example shows the possible predetermination of
      stereochemistry for complexes by ligands based on a glycoscaffold.

PMID- 18321041
TI  - An experimental and theoretical study of the variation of 4f hybridization across
      the La1-xCexIn3 series.
AB  - Crystal structures of a series of La(1-x)Ce(x)In(3) (x = 0.02, 0.2, 0.5, or 0.8)
      intermetallic compounds have been investigated by both neutron and X-ray
      diffraction, and their physical properties have been characterized by magnetic
      susceptibility and specific heat measurements. Our results emphasize atypical
      atomic displacement parameters (ADP) for the In and the rare-earth sites.
      Depending on the x value, the In ADP presents either an "ellipsoidal" elongation
      (La-rich compounds) or a "butterfly-like" distortion (Ce-rich compounds). These
      deformations have been understood by theoretical techniques based on the band
      theory and are the result of hybridization between conduction electrons and 4f
      electrons.

PMID- 18321042
TI  - Design and synthesis of a caged Zn2+ probe, 8-benzenesulfonyloxy-5-N,N
      dimethylaminosulfonylquinolin-2-ylmethyl-pendant 1,4,7,10-tetraazacyclododecane,
      and its hydrolytic uncaging upon complexation with Zn2+.
AB  - 8-Benzenesulfonyloxy-5- N,N-dimethylaminosulfonylquinolin-2-ylmethyl-pendant
      cyclen (BS-caged-L(4), BS = benzenesulfonyl) was designed and synthesized as a
      "caged" derivative of a previously described Zn(2+) fluorophore, 8-hydroxy-5- N,N
      dimethylaminosulfonylquinolin-2-ylmethyl-pendant cyclen (L(4)) (cyclen = 1,4,7,10
      tetraazacyclododecane). In the absence of metal ions and in the dark, BS-caged
      L(4) (10 microM) showed negligible fluorescence emission at pH 7.4 (10 mM HEPES
      with I = 0.1 (NaNO3)) and 25 degrees C (excitation at 328 nm). Addition of Zn(2+)
      induced an increase in the UV/vis absorption of BS-caged-L(4) (10 microM) at 258
      nm and a significant increase in fluorescence emission at 512 nm. These responses
      are results from the formation of Zn(H-1L(4)) by the hydrolysis of the sulfonyl
      ester at the 8-position of the quinoline unit promoted by the Zn(2+)-bound HO(-).
      Improvement of cell membrane permeation in comparison with L(4) is also
      described.

PMID- 18321043
TI  - Effect of pi-conjugated length of bridging ligand on the optoelectronic
      properties of platinum(II) dimers.
AB  - We report a quantum-chemical study of the electronic and optical properties of
      several platinum(II) dimers, [Pt(pip2NCN)]2(L)(2+) (pip2NCNH = 1,3
      bis(piperidylmethyl)benzene, L represents the bridging ligands pyrazine, 4,4'
      bipyridine, or trans-1,2-bis(4-pyridyl)ethylene). The theoretical calculations
      reveal that as the pi-conjugated length of bridging ligand increases, the
      energies of HOMOs and LUMOs, bonding energy of Pt-N bridge, and the largest
      absorption strength increase whereas the ionization potentials decrease.
      According to the inner reorganization energy and density of states, we presume
      the hole-transporting properties of these dimers is better than the electron
      transporting, and their inner reorganization energies for hole transport are
      lower than that of 4,4'-bis(phenyl-m-tolylamino)biphenyl (TPD), a well-known hole
      transporting material. These platinum(II) dimers, especially
      [Pt(pip2NCN)]2(bpe)(2+), hold promise for use as a new kind of third-order
      nonlinear optical material, owing to their large third-order polarizabilty value
      and high transparency. Moreover, the optoelectronic properties of these complexes
      are easy to tailor by modifying the peripheral and central ligands. These
      theoretical results are beneficial to the design of new functional materials with
      excellent optoelectronic properties.

PMID- 18321044
TI  - Incorporation of substitutionally labile [V(III)(CN)6]3- into prussian blue type
      magnetic materials.
AB  - A Prussian blue (PB) type material containing hexacyanovanadate(III),
      Mn(II)1.5[V(III)(CN)6].(0.30)MeCN (1), was formed from the reaction of
      [V(III)(CN)6](3-) with [Mn(NCMe)6](2+) in MeCN. This new material exhibits
      ferrimagnetic spin- or cluster-glass behavior below a Tc of 12K with observed
      magnetic hysteresis at 2 K (Hcr = 65 Oe and Mrem = 730 emu.Oe/mol). Reactions of
      [V(III)(CN)6](3-) with [M(II)(NCMe)6](2+) (M = Fe, Co, Ni) in MeCN lead to either
      partial (M = Co) or complete (M = Fe, Ni) linkage isomerization, resulting in
      compounds of Fe(II)(0.5)V(III)[Fe(II)(CN)6].(0.85)MeCN (2),
      (NEt4)(0.10)Co(II)(1.5- a)V(II)a[Co(III)(CN)6]a [V(III)(CN)6](1
      a)(BF4)(0.10).(0.35)MeCN (3), and (NEt4)(0.20)V(III)[Ni(II)(CN)4](1.6).(0.10)MeCN
      (4) compositions. Compounds 2-4 do not magnetically order as a consequence of
      diamagnetic cyanometalate anions being present, i.e., [Fe(II)(CN)6](4-),
      [Co(III)(CN)6](3-), and [Ni(II)(CN)4](2-). Incorporation of [V(III)(CN)6](3-)
      into PB-type materials is synthetically challenging because of the lability of
      the cyanovanadate(III) anion.

PMID- 18321045
TI  - Synthesis and magnetic properties of a [Ni(II)(TCNE)(NCMe)2-delta][BF4] magnet
      (Tc = 40 K).
AB  - The reaction of (NBu4)(TCNE) (TCNE = tetracyanoethylene) and [Ni(NCMe)6][BF4]2 in
      CH2Cl2 forms layered [Ni(TCNE)(MeCN)2-delta][BF4], a magnet ( Tc = 40 K) with a
      ferromagnetic interaction within Ni-mu 4-[TCNE](*-) layers, and a new general
      route to the preparation of [M(TCNE)(NCMe)2][anion] magnets has been identified.

PMID- 18321046
TI  - Synthesis and photophysical properties of ruthenium-based dendrimers and their
      use in dye sensitized solar cells.
AB  - First- and second-generation dendrimers (Ru3 and Ru6) have been synthesized, and
      their photophysical properties were investigated in solution and when adsorbed on
      the nanocrystalline TiO2 surface. The performance of Ru3 and Ru6 as charge
      transfer photosensitizers in nanocrytalline TiO2 based solar cells was also
      investigated. The best photovoltaic performance was obtained by the Ru3 based
      solar cell yielding a short circuit current of J sc = 5.52 mA.cm (-2) and an open
      circuit voltage of V oc = 626 mV, corresponding to an overall conversion
      efficiency of eta = 1.80% that is approximately double the conversion efficiency
      of the reference compound Ru1 (eta = 0.91%) and of the second generation
      dendrimer Ru6 (eta = 0.95%). The particular efficiency of the first generation
      dendrimer, Ru3, is attributed to the better light-harvesting properties of the
      doped nanocrystalline TiO2 film when compared to Ru1, whereas the poor
      performance of the second generation dendrimer, Ru6, is attributed to the uneven
      adsorption of all of the ruthenium moieties to the nanocrystalline TiO2 surface
      at the same time.

PMID- 18321047
TI  - Copper fungicide residues in Australian vineyard soils.
AB  - Copper (Cu) concentrations were measured in Australian vineyard soils to assess
      the extent and magnitude of Cu accumulation resulting from the use of Cu-based
      fungicides and to indicate the likely risks to long-term soil fertility. Soil
      samples were collected from 98 vineyards across 10 grape-growing regions of
      Australia and analyzed for total Cu concentrations. Ninety-six percent of
      vineyards surveyed had elevated Cu concentrations in soil compared to the
      background Cu concentrations in nearby soil in its native state. Concentrations
      of total B, Co, Cr, Pb, and Zn were similar to background concentrations and
      below reported toxicity guideline values. Cu concentrations in Australian
      vineyard soils were generally much lower (6-150 mg kg (-1)) than those reported
      in the soils of vineyards in parts of Europe (i.e., 130-1280 mg kg (-1)).
      Concentrations of total Cu were generally below those concentrations reported to
      cause lethal effects to soil invertebrates; however, Cu exceeded concentrations
      known to cause sublethal effects (i.e., inhibit growth, affect reproduction,
      induce avoidance behavior) to those (or related) invertebrates.

PMID- 18321048
TI  - Reduction of ochratoxin a levels in red wine by bentonite, modified bentonites,
      and chitosan.
AB  - Adsorption method may play an important role to remove ochratoxin A (OTA) from
      wine by bentonite (B), nonylammonium bentonite (NB), dodecylammonium bentonite
      (DB), KSF-montmorillonite (KSF), and chitosan bead (CB). The optimum conditions
      of OTA adsorption from synthetic solutions were revealed at room temperature and
      pH 3.5. The adsorption equilibria of B and NB were almost established within 120
      and 240 min, respectively. DB, KSF, and CB had about 90 min of equilibration
      time. The adsorption efficiency carried out in the synthetic OTA solution did not
      change remarkably when the amounts of adsorbents were 25 mg for bentonite, DB,
      and KSF and 100 mg for NB and CB. Furthermore, 25 mg of adsorbents was used at
      all adsorption studies in synthetic solution. The adsorption isotherm was fitted
      with mostly a Freundlich equation with respect to the correlation coefficients.
      The adsorption data were evaluated using Langmuir and Freundlich equations having
      Kf values ranging from 0.011 to 9.5 with respect to correlation coefficients (R2
      = 0.900-0.977). DB and KSF have the highest adsorption capacity for OTA in
      synthetic solutions. In wine, the removal of OTA was succeeded at a percentage of
      60-100 by KSF and CB. Furthermore, the highest adsorption capacity of OTA for red
      wine was obtained by using 250 mg of KSF, which caused less damage to the nature
      of wine and also low adsorption of polyphenols and anthcyans.

PMID- 18321049
TI  - Anti-inflammatory effect of spilanthol from Spilanthes acmella on murine
      macrophage by down-regulating LPS-induced inflammatory mediators.
AB  - Spilanthes acmella (Paracress), a common spice, has been administered as a
      traditional folk medicine for years to cure toothaches, stammering, and
      stomatitis. Previous studies have demonstrated its diuretic, antibacterial, and
      anti-inflammatory activities. However, the active compounds contributing to the
      anti-inflammatory effect have seldom been addressed. This study isolates the
      active compound, spilanthol, by a bioactivity-guided approach and indicates
      significant anti-inflammatory activity on lipopolysaccharide-activated murine
      macrophage model, RAW 264.7. The anti-inflammatory mechanism of paracress is also
      investigated. Extracts of S. acmella are obtained by extraction with 85% ethanol,
      followed by liquid partition against hexane, chloroform, ethyl acetate, and
      butanol. The ethyl acetate extract exhibits a stronger free radical scavenging
      capacity than other fractions do, as determined by DPPH and ABTS radical
      scavenging assays. The chloroform extract significantly inhibits nitric oxide
      production ( p < 0.01) and is selected for further fractionation to yield the
      active compound, spilanthol. The diminished levels of LPS-induced inducible
      nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) mRNA and protein
      expression support the postulation that spilanthol inhibits proinflammatory
      mediator production at the transcriptional and translational levels.
      Additionally, the LPS-stimulated IL-1beta, IL-6, and TNF-alpha productions are
      dose-dependently reduced by spilanthol. The LPS-induced phosphorylation of
      cytoplasmic inhibitor-kappaB and the nuclear NF-kappaB DNA binding activity are
      both restrained by spilanthol. Results of this study suggest that spilanthol,
      isolated from S. acmella, attenuates the LPS-induced inflammatory responses in
      murine RAW 264.7 macrophages partly due to the inactivation of NF-kappaB, which
      negatively regulates the production of proinflammatory mediators.

PMID- 18321050
TI  - A comparative study of flavonoid compounds, vitamin C, and antioxidant properties
      of baby leaf Brassicaceae species.
AB  - A comparative study of antioxidant compounds, flavonoids and vitamin C, and also
      antioxidant activity was carried out in four species of Brassicaceae vegetables
      used for salads: watercress ( Nasturtium officinale R. Br.), mizuna [ Brassica
      rapa L. subsp. nipposinica (L.H. Bailey) Haneltand], wild rocket [ Diplotaxis
      tenuifolia (L.) DC.], and salad rocket [ Eruca vesicaria (L.) Cav.]. The
      characterization of individual phenolic compounds by HPLC-DAD-MS/MS-ESI in
      watercress and mizuna completes the polyphenol study previously reported for wild
      rocket and salad rocket. The qualitative study of flavonoids in watercress leaves
      showed a characteristic glycosylation pattern with rhamnose at the 7 position.
      Isorhamnetin 3,7-di- O-glucoside was identified in mizuna leaves and may be
      considered a chemotaxonomical marker in some B. rapa subspecies. Brassicaceae
      species showed differences in the quantitative study of flavonoids, and the
      highest content was detected in watercress leaves. Watercress and wild rocket
      leaves had the highest content of vitamin C. The antioxidant activity evaluated
      by different methods (ABTS, DPPH, and FRAP assays) showed a high correlation
      level with the content of polyphenols and vitamin C. In conclusion, the
      Brassicaceae leaves studied, watercress, mizuna, wild rocket, and salad rocket,
      presented a large variability in the composition and content of antioxidant
      compounds. These baby leaf species are good dietary sources of antioxidants with
      an important variability of bioactive compounds.

PMID- 18321051
TI  - Changes in virgin olive oil quality during low-temperature fruit storage.
AB  - 'Frantoio' olive fruits were stored at low temperature (4 +/- 2 degrees C) for 3
      weeks to investigate the effect of postharvest fruit storage on virgin olive oil
      quality. Volatile compounds and phenolic compounds explained the changes in
      sensory quality that could not be explained with quality indices (FFA, PV, K232,
      and K270). Increases in concentrations of ( E)-2-hexenal and hexanal corresponded
      to positive sensory quality, whereas increases in ( E)-2-hexenol and (+)
      acetoxypinoresinol were associated with negative sensory quality. Volatile and
      phenolic compounds were also indicative of the period of low-temperature fruit
      storage. Oleuropein and ligstroside derivatives in olive oil decreased with
      respect to storage time, and their significant ( p < 0.05) change corresponded to
      changes in bitterness and pungency. ( Z)-2-Penten-1-ol increased during low
      temperature fruit storage, whereas 2-pentylfuran decreased. Changes in volatile
      compounds, phenolic compounds, quality indices, and sensory notes indicated that
      virgin olive oil quality was lost within the first week of low-temperature fruit
      storage and regained at 2 weeks. This research suggests that low-temperature
      olive fruit storage may be beneficial, with a possibility of increasing oil yield
      and moderating the sensory quality of virgin olive oils. This study demonstrates
      that deeper insights into virgin olive oil quality changes during low-temperature
      fruit storage may be gained by studying volatile and phenolic compounds in
      addition to quality indices and physical appearance of the fruit.

PMID- 18321052
TI  - Activity of alpha-amylase inhibitors from Phaseolus coccineus on digestive alpha
      amylases of the coffee berry borer.
AB  - Seeds of scarlet runner bean ( Phaseolus coccineus L.) were analyzed for alpha
      amylase inhibitor (alpha-AI) activity. Through the use of polyclonal antibodies
      raised against pure alpha-AI-1 from common bean ( Phaseolus vulgaris L.), typical
      alpha-AlphaIota polypeptides (Mr 14-18 kDa) as well as a large polypeptide of Mr
      32000 Da, usually referred to as "amylase inhibitor like", were detected. The
      inhibitor activity present in four accessions of P. coccineus was examined, both
      in semiquantitative zymograms allowing the separation of different isoforms and
      in quantitative assays against human salivary amylase, porcine pancreatic
      amylase, and coffee berry borer, Hypothenemus hampei Ferrari (Coleoptera:
      Scolytidae) amylase. Differential inhibition curves lead to the suggestion that
      the gene encoding one of the inhibitors in P. coccineus (in accession G35590)
      would be a good candidate for genetic engineering of coffee resistance toward the
      coffee berry borer. An in vitro proteolytic digestion treatment of pure alpha
      AlphaIota-1 resulted in a rapid loss of the inhibitory activity, seriously
      affecting its natural capacity to interact with mammalian alpha-amylases.

PMID- 18321053
TI  - Simple and efficient method for the estimation of residues of flubendiamide and
      its metabolite desiodo flubendiamide.
AB  - An analytical method was standardized for the estimation of residues of
      flubendiamide and its metabolite desiodo flubendiamide in various substrates
      comprising cabbage, tomato, pigeonpea grain, pigeonpea straw, pigeonpea shell,
      chilli, and soil. The samples were extracted with acetonitrile, diluted with
      brine solution, and partitioned into chloroform, dried over anhydrous sodium
      sulfate, and treated with 500 mg of activated charcoal powder. Final clear
      extracts were concentrated under vacuum and reconstituted into HPLC grade
      acetonitrile, and residues were estimated using HPLC equipped with a UV detector
      at 230 lambda and a C18 column. Acetonitrile/water (60:40 v/v) at 1 mL/min was
      used as mobile phase. Both flubendiamide and desiodo flubendiamide presented
      distinct peaks at retention times of 11.07 and 7.99 min, respectively. Consistent
      recoveries ranging from 85 to 99% for both compounds were observed when samples
      were spiked at 0.10 and 0.20 mg/kg levels. The limit of quantification of the
      method was worked out to be 0.01 mg/kg.

PMID- 18321054
TI  - Effects of sonication on the kinetics of orange juice quality parameters.
AB  - The effects of sonication on pH, degrees Brix, titratable acidity (TA), cloud,
      browning index, and color parameters ( L*, a*, and b*) of freshly squeezed orange
      juice samples were studied. Ultrasonic intensity (UI) levels of 8.61, 9.24,
      10.16, 17.17, and 22.79 W/cm2 and treatment times of 0 (control), 2, 4, 6, 8, and
      10 min were investigated. No significant changes in pH, degrees Brix, and TA ( p
      < 0.05) were found. Cloud value, browning index, and color parameters were
      significantly affected by ultrasonic intensity and treatment time. Changes in
      cloud value followed first-order kinetics, whereas browning index, L*, a*, and b*
      values followed zero-order kinetics. Reaction rate constants were linearly
      correlated ( R2 > 0.90) to ultrasonic intensity.

PMID- 18321055
TI  - Submerged citric acid fermentation on orange peel autohydrolysate.
AB  - The citrus-processing industry generates in the Mediterranean area huge amounts
      of orange peel as a byproduct from the industrial extraction of citrus juices. To
      reduce its environmental impact as well as to provide an extra profit, this
      residue was investigated in this study as an alternative substrate for the
      fermentative production of citric acid. Orange peel contained 16.9% soluble
      sugars, 9.21% cellulose, 10.5% hemicellulose, and 42.5% pectin as the most
      important components. To get solutions rich in soluble and starchy sugars to be
      used as a carbon source for citric acid fermentation, this raw material was
      submitted to autohydrolysis, a process that does not make use of any acidic
      catalyst. Liquors obtained by this process under optimum conditions (temperature
      of 130 degrees C and a liquid/solid ratio of 8.0 g/g) contained 38.2 g/L free
      sugars (8.3 g/L sucrose, 13.7 g/L glucose, and 16.2 g/L fructose) and significant
      amounts of metals, particularly Mg, Ca, Zn, and K. Without additional nutrients,
      these liquors were employed for citric acid production by Aspergillus niger CECT
      2090 (ATCC 9142, NRRL 599). Addition of calcium carbonate enhanced citric acid
      production because it prevented progressive acidification of the medium.
      Moreover, the influence of methanol addition on citric acid formation was
      investigated. Under the best conditions (40 mL of methanol/kg of medium), an
      effective conversion of sugars into citric acid was ensured (maximum citric acid
      concentration of 9.2 g/L, volumetric productivity of 0.128 g/(L.h), and yield of
      product on consumed sugars of 0.53 g/g), hence demonstrating the potential of
      orange peel wastes as an alternative raw material for citric acid fermentation.

PMID- 18321056
TI  - Pyridinium alkaloid-coupled secoiridoids from the flower buds of Lonicera
      japonica.
AB  - Three pyridinium inner salt alkaloids, lonijaposides A-C (1-3), based on an
      unprecedented skeleton of an N-substituted nicotinic acid nucleus coupled through
      C-5 with C-7 of a secoiridoid, together with seven known iridoids, have been
      isolated from the flower buds of Lonicera japonica. Their structures were
      elucidated by spectroscopic and chemical analyses. Lonijaposide C (3) showed
      activity against the release of glucuronidase in rat polymorphonuclear leukocytes
      induced by the platelet-activating factor.

PMID- 18321057
TI  - Cytotoxic diterpenoids from Euphorbia helioscopia.
AB  - Four new jatrophane-type diterpenoids (1-4), together with 16 known related
      compounds, were isolated from the Chinese medicinal plant Euphorbia helioscopia.
      The structures of 1-4 were determined on the basis of spectroscopic and chemical
      methods. Cytotoxicity of the isolated compounds against HeLa and MDA-MB-231 cells
      was evaluated, with only helioscopinolide A (5) and euphornin (3a) being active.

PMID- 18321058
TI  - Pittosporumxanthins, cycloaddition products of carotenoids with alpha-tocopherol
      from seeds of Pittosporum tobira.
AB  - A series of carotenoid-alpha-tocopherol cycloaddition products, named
      pittosporumxanthins B1 ( 3), B2 ( 4), C1 ( 5), C2 ( 6), A3 ( 7), and A4 ( 8),
      were isolated from the seeds of Pittosporum tobira. The structures were
      determined to be cycloaddition products of 9' Z-antheraxanthin at the 11' and 12'
      positions with alpha-tocopherol ( 3 and 4), 9' Z-neoaxanthin with alpha
      tocopherol ( 5 and 6), and 9 Z-violaxanthin with alpha-tocopherol ( 7 and 8) on
      the basis of a detailed analyses of MS and NMR spectroscopic data. The
      configurations of the carotenoid end groups in the pittosporumxanthins were
      determined by a modified Mosher's method. Compounds 3, 5, and 7 were assigned
      (11' R,12' S) and 4, 6, and 8 (11' S,12' R) absolute configurations using CD
      measurements.

PMID- 18321059
TI  - Salinipyrones and pacificanones, mixed-precursor polyketides from the marine
      actinomycete Salinispora pacifica.
AB  - Chemical examination of a phylogenetically unique strain of the obligate marine
      actinomycete Salinispora pacifica led to the discovery of four new polyketides,
      salinipyrones A and B ( 1, 2) and pacificanones A and B ( 3, 4). These compounds
      appear to be derived from a mixed-precursor polyketide biosynthesis involving
      acetate, propionate, and butyrate building blocks. Spectral analysis, employing
      NMR, IR, UV, and CD methods and chemical derivatization, was used to assign the
      structures and absolute configurations of these new metabolites. Salinipyrones A
      and B displayed exactly opposite CD spectra, indicating their pseudoenantiomeric
      relationship. This relationship was shown to be a consequence of the geometric
      isomerization of one double bond. The phenomenon of polyketide module skipping is
      proposed to explain the unusual biosynthesis of the salinipyrones and the
      pacificanones.

PMID- 18321060
TI  - Introduction to the William A. Lester, Jr., Festschrift.

PMID- 18321066
TI  - Ubiquitylation of proliferating cell nuclear antigen and recruitment of human DNA
      polymerase eta.
AB  - This study investigated the requirement for ubiquitylation of PCNA at lysine 164
      during polymerase eta-dependent translesion synthesis (TLS) of site-specific cis
      syn cyclobutane thymine dimers (T (wedge)T). The in vitro assay recapitulated
      origin-dependent initiation, fork assembly, and semiconservative, bidirectional
      replication of double-stranded circular DNA substrates. A phosphocellulose column
      was used to fractionate HeLa cell extracts into two fractions; flow-through
      column fraction I (CFI) contained endogenous PCNA, RPA, ubiquitin-activating
      enzyme E1, and ubiquitin conjugase Rad6, and eluted column fraction II (CFII)
      included pol delta, pol eta, and RFC. CFII supplemented with purified recombinant
      RPA and PCNA (wild type or K164R, in which lysine was replaced with arginine) was
      competent for DNA replication and TLS. K164R-PCNA complemented CFII for these
      activities to the same extent and efficiency as wild-type PCNA. CFII mixed with
      CFI (endogenous PCNA, E1, Rad6) exhibited enhanced DNA replication activity, but
      the same TLS efficiency determined with the purified proteins. These results
      demonstrate that PCNA ubiquitylation at K164 of PCNA is not required in vitro for
      pol eta to gain access to replication complexes at forks stalled by T (wedge)T
      and to catalyze TLS across this dimer.

PMID- 18321067
TI  - Characterization of the neuron-specific L1-CAM cytoplasmic tail: naturally
      disordered in solution it exercises different binding modes for different adaptor
      proteins.
AB  - L1, a highly conserved transmembrane glycoprotein member of the immunoglobulin
      superfamily of cell adhesion molecules, mediates many developmental processes in
      the nervous system. Here we present the biophysical characterization and the
      binding properties of the least structurally defined part of this receptor: its
      cytoplasmic tail (CT). We have shown by analytical ultracentrifugation and
      dynamic light scattering experiments that it is mostly monomeric and unstructured
      in aqueous solution. We have defined by nuclear magnetic resonance the molecular
      details of L1-CT binding to two major targets: a membrane-cytoskeletal linker
      (MCL), ezrin, and an endocytosis mediator, AP2. Surprisingly, in addition to the
      two previously identified ezrin binding motifs, the juxtamembrane and the
      (1176)YRSLE regions, we have discovered a third one, a part of which has been
      previously associated with binding to another MCL, ankyrin. For the L1
      interaction with AP2 we have determined the precise interaction region
      surrounding the (1176)YRSLE binding site and that this overlaps with the second
      ezrin binding site. In addition, we have shown that the juxtamembrane region of
      L1-CT has some binding affinity to AP2-mu2, although the specificity of this
      interaction needs further investigation. These data indicate that L1-CT belongs
      to the class of intrinsically disordered proteins. Endogenous flexibility of L1
      CT might play an important role in dynamic regulation of intracellular signaling:
      the ability of cytoplasmic tails to accommodate different targets has the
      potential to fine-tune signal transduction via cell surface receptors.

PMID- 18321068
TI  - Active internal waters in the bacteriorhodopsin photocycle. A comparative study
      of the L and M intermediates at room and cryogenic temperatures by infrared
      spectroscopy.
AB  - We present time-resolved room-temperature infrared difference spectra for the
      bacteriorhodopsin (bR) photocycle at 8 cm (-1) spectral and 5 micros temporal
      resolution, from 4000 to 800 cm (-1). An in situ hydration method allowed for a
      controlled and stable sample hydration (92% relative humidity), largely improving
      the quality of the data without affecting the functionality of bR. Experiments in
      both H 2 (16)O and H 2 (18)O were conducted to assign bands to internal water
      molecules. Room-temperature difference spectra of the L and M intermediates minus
      the bR ground state (L-BR and M-BR, respectively) were comprehensively compared
      with their low-temperature counterparts. The room-temperature M-BR spectrum was
      almost identical to that obtained at 230 K, except for a continuum band. The
      continuum band contains water vibrations from this spectral comparison between H
      2 (16)O and H 2 (18)O, and no continuum band at 230 K suggests that the
      protein/solvent dynamics are insufficient for deprotonation of the water cluster.
      On the other hand, an intense positive broadband in the low-temperature L-BR
      spectrum (170 K) assigned to the formation of a water cavity in the cytoplasmic
      domain is absent at room temperature. This water cavity, proposed to be an
      essential feature for the formation of L, seems now to be a low-temperature
      artifact caused by restricted protein dynamics at 170 K. The observed differences
      between low- and room-temperature FTIR spectra are further discussed in light of
      previously reported dynamic transitions in bR. Finally, we show that the kinetics
      of the transient heat relaxation of bR after photoexcitation proceeds as a
      thermal diffusion process, uncorrelated with the photocycle itself.

PMID- 18321069
TI  - Kinetic mechanism of phenylacetone monooxygenase from Thermobifida fusca.
AB  - Phenylacetone monooxygenase (PAMO) from Thermobifida fusca is a FAD-containing
      Baeyer-Villiger monooxygenase (BVMO). To elucidate the mechanism of conversion of
      phenylacetone by PAMO, we have performed a detailed steady-state and pre-steady
      state kinetic analysis. In the catalytic cycle ( k cat = 3.1 s (-1)), rapid
      binding of NADPH ( K d = 0.7 microM) is followed by a transfer of the 4( R)
      hydride from NADPH to the FAD cofactor ( k red = 12 s (-1)). The reduced PAMO is
      rapidly oxygenated by molecular oxygen ( k ox = 870 mM (-1) s (-1)), yielding a
      C4a-peroxyflavin. The peroxyflavin enzyme intermediate reacts with phenylacetone
      to form benzylacetate ( k 1 = 73 s (-1)). This latter kinetic event leads to an
      enzyme intermediate which we could not unequivocally assign and may represent a
      Criegee intermediate or a C4a-hydroxyflavin form. The relatively slow decay (4.1
      s (-1)) of this intermediate yields fully reoxidized PAMO and limits the turnover
      rate. NADP (+) release is relatively fast and represents the final step of the
      catalytic cycle. This study shows that kinetic behavior of PAMO is significantly
      different when compared with that of sequence-related monooxygenases, e.g.,
      cyclohexanone monooxygenase and liver microsomal flavin-containing monooxygenase.
      Inspection of the crystal structure of PAMO has revealed that residue R337, which
      is conserved in other BVMOs, is positioned close to the flavin cofactor. The
      analyzed R337A and R337K mutant enzymes were still able to form and stabilize the
      C4a-peroxyflavin intermediate. The mutants were unable to convert either
      phenylacetone or benzyl methyl sulfide. This demonstrates that R337 is crucially
      involved in assisting PAMO-mediated Baeyer-Villiger and sulfoxidation reactions.

PMID- 18321070
TI  - Chemical mechanism of homoisocitrate dehydrogenase from Saccharomyces cerevisiae.
AB  - Homoisocitrate dehydrogenase (HIcDH, 3-carboxy-2-hydroxyadipate dehydrogenase)
      catalyzes the fourth reaction of the alpha-aminoadipate pathway for lysine
      biosynthesis, the conversion of homoisocitrate to alpha-ketoadipate using NAD as
      an oxidizing agent. A chemical mechanism for HIcDH is proposed on the basis of
      the pH dependence of kinetic parameters, dissociation constants for competitive
      inhibitors, and isotope effects. According to the pH-rate profiles, two enzyme
      groups act as acid-base catalysts in the reaction. A group with a p K a of
      approximately 6.5-7 acts as a general base accepting a proton as the beta-hydroxy
      acid is oxidized to the beta-keto acid, and this residue participates in all
      three of the chemical steps, acting to shuttle a proton between the C2 hydroxyl
      and itself. The second group acts as a general acid with a p K a of 9.5 and
      likely catalyzes the tautomerization step by donating a proton to the enol to
      give the final product. The general acid is observed in only the V pH-rate
      profile with homoisocitrate as a substrate, but not with isocitrate as a
      substrate, because the oxidative decarboxylation portion of the isocitrate
      reaction is limiting overall. With isocitrate as the substrate, the observed
      primary deuterium and (13)C isotope effects indicate that hydride transfer and
      decarboxylation steps contribute to rate limitation, and that the decarboxylation
      step is the more rate-limiting of the two. The multiple-substrate deuterium/
      (13)C isotope effects suggest a stepwise mechanism with hydride transfer
      preceding decarboxylation. With homoisocitrate as the substrate, no primary
      deuterium isotope effect was observed, and a small (13)C kinetic isotope effect
      (1.0057) indicates that the decarboxylation step contributes only slightly to
      rate limitation. Thus, the chemical steps do not contribute significantly to rate
      limitation with the native substrate. On the basis of data from solvent deuterium
      kinetic isotope effects, viscosity effects, and multiple-solvent deuterium/ (13)C
      kinetic isotope effects, the proton transfer step(s) is slow and likely reflects
      a conformational change prior to catalysis.

PMID- 18321071
TI  - Structure of the integrin beta3 transmembrane segment in phospholipid bicelles
      and detergent micelles.
AB  - Integrin adhesion receptors transduce bidirectional signals across the plasma
      membrane, with the integrin transmembrane domains acting as conduits in this
      process. Here, we report the first high-resolution structure of an integrin
      transmembrane domain. To assess the influence of the membrane model system,
      structure determinations of the beta3 integrin transmembrane segment and flanking
      sequences were carried out in both phospholipid bicelles and detergent micelles.
      In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-H772, is
      adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This
      relatively long transmembrane helix implies a pronounced helix tilt within a
      typical lipid bilayer, which facilitates the snorkeling of K716's charged side
      chain out of the lipid core while simultaneously immersing hydrophobic L717-I721
      in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to
      the transfer of L717-I721 into the aqueous phase, suggesting that the reported
      embedding represents the preferred beta3 state. The nature of the lipid headgroup
      affected only the intracellular part of the transmembrane helix, indicating that
      an asymmetric lipid distribution is not required for studying the beta3
      transmembrane segment. In the micelle, residues L717-I721 are also embedded but
      deviate from linear alpha-helical conformation in contrast to I693-K716, which
      closely resemble the bicelle structure.

PMID- 18321072
TI  - Comprehensive X-ray structural studies of the quinolinate phosphoribosyl
      transferase (BNA6) from Saccharomyces cerevisiae.
AB  - Quinolinic acid phosphoribosyl transferase (QAPRTase, EC 2.4.2.19) is a 32 kDa
      enzyme encoded by the BNA6 gene in yeast and catalyzes the formation of
      nicotinate mononucleotide from quinolinate and 5-phosphoribosyl-1-pyrophosphate
      (PRPP). QAPRTase plays a key role in the tryptophan degradation pathway via
      kynurenine, leading to the de novo biosynthesis of NAD (+) and clearing the
      neurotoxin quinolinate. To improve our understanding of the specificity of the
      eukaryotic enzyme and the course of events associated with catalysis, we have
      determined the crystal structures of the apo and singly bound forms with the
      substrates quinolinate and PRPP. This reveals that the enzyme folds in a manner
      similar to that of various prokaryotic forms which are approximately 30%
      identical in sequence. In addition, the structure of the Michaelis complex is
      approximated by PRPP and the quinolinate analogue phthalate bound to the active
      site. These results allow insight into the kinetic mechanism of QAPRTase and
      provide an understanding of structural diversity in the active site of the
      Saccharomyces cerevisiae enzyme when compared to prokaryotic homologues.

PMID- 18321073
TI  - Super-resolution imaging by random adsorbed molecule probes.
AB  - Single molecule localization (SML) is a powerful tool to measure the position and
      trajectory of molecules in numerous systems, with nanometer accuracy. This
      technique has been recently utilized to overcome the diffraction limit in optical
      imaging. So far, super-resolution imaging by SML was demonstrated using
      photoactivable or photoswitchable fluorophores, as well as diffusive fluorophore
      probes in solution. All these methods, however, rely on special fluorophore or
      object properties. In this Letter, we propose and demonstrate a new super
      resolution technique attainable for a bio/dielectric structure on a metal
      substrate. A sub-diffraction-limited image is obtained by randomly adsorbed
      fluorescent probe molecules on a liquid-solid interface, while the metal
      substrate, quenching the unwanted fluorescent signal, provides a significantly
      enhanced imaging contrast. As this approach does not use specific stain
      techniques, it can be readily applied to general dielectric objects, such as
      nanopatterned photoresist, inorganic nanowires, subcellular structures, etc.

PMID- 18321074
TI  - Direct transmission detection of tunable mechanical resonance in an individual
      carbon nanofiber relay.
AB  - A direct on-chip transmission measurement of the resonance frequency of an
      individual singly clamped carbon nanofiber relay is reported. The experimental
      results are in good agreement with a small signal model and show the expected
      tuning of the resonance frequency with changing bias voltage.

PMID- 18321076
TI  - Diameter dependent growth rate and interfacial abruptness in vapor-liquid-solid
      Si/Si1-xGex heterostructure nanowires.
AB  - A strong diameter dependence is observed in the interfacial abruptness and growth
      rates in Si/Si 1- x Ge x axial heterostructure nanowires grown via Au-mediated
      low pressure CVD using silane and germane precursors. The growth of these
      nanowires has similarities to that of heterostructure thin films with similar
      compositional interfacial broadening, which increases with and is on the order
      with diameter. This broadening may reveal a fundamental challenge to fabrication
      of abrupt heterostructures via VLS growth.

PMID- 18321075
TI  - Nanomechanical control of cell rolling in two dimensions through surface
      patterning of receptors.
AB  - We envisioned that label-free control of the transport of cells in two dimensions
      through receptor-ligand interactions would enable simple separation systems that
      are easy to implement yet retain the specificity of receptor-ligand interactions.
      Here we demonstrate nanomechanical control of cell transport in two dimensions
      via transient receptor-ligand adhesive bonds by patterning of receptors that
      direct cell rolling through an edge effect. HL-60 cells rolling on P-selectin
      receptor patterns were deflected at angles of 5-10 degrees with respect to their
      direction of travel. Absence of this effect in the case of rigid microsphere
      models of cell rolling suggests that this two-dimensional motion depends on
      nanomechanical properties of the rolling cell. This work suggests the feasibility
      of simple continuous-flow microfluidic cell separation systems that minimize
      processing steps and yet retain the specificity of receptor-ligand interactions.

PMID- 18321077
TI  - Hyperfine interactions in graphene and related carbon nanostructures.
AB  - Hyperfine interactions, magnetic interactions between the spins of electrons and
      nuclei, in graphene and related carbon nanostructures are studied. By using a
      combination of accurate first principles calculations on graphene fragments and
      statistical analysis, I show that both isotropic and dipolar hyperfine
      interactions in sp2 carbon nanostructures can be accurately described in terms of
      the local electron spin distribution and atomic structure. A complete set of
      parameters describing the hyperfine interactions of 13C and other nuclear spins
      at substitution impurities and edge terminations is determined. These results
      permit the design of graphene-based nanostructures allowing for longer electron
      spin coherence times which are required by spintronics and quantum information
      processing applications. Practical recipes for minimizing hyperfine interactions
      in carbon nanostructures are given.

PMID- 18321078
TI  - Label-free sequence-specific DNA sensing using copper-enhanced anodic stripping
      of purine bases at boron-doped diamond electrodes.
AB  - Stripping voltammetric determination of purine bases in the presence of copper
      ions at mercury, amalgam, or carbon-based electrodes has recently been utilized
      in analysis of DNA or synthetic oligodeoxynucleotides (ODNs). Here we report on
      copper-enhanced label-free anodic stripping detection of guanine and adenine
      bases in acid-hydrolyzed DNA at anodically oxidized boron-doped diamond electrode
      (AO-BDDE). The AO-BDDE was successfully applied in a three-electrode microcell in
      which an approximately 50 microL drop of the analyte solution can be efficiently
      stirred during the accumulation step by streaming of an inert gas. Accelerated
      mass transport due to the solution motion in the presence of copper resulted in
      enhancement of the guanine oxidation signal by about 2 orders of magnitude
      (compared to accumulation of the analyte from still solution not containing
      copper), allowing an easy detection of approximately 25 fmol of the ODNs. The
      proposed technique is shown to be suitable for a determination of purine
      (particularly guanine) content in DNA samples. Applications of the technique in
      magnetic bead-based DNA assays (such as hybridization with DNA sequences
      exhibiting asymmetrical distribution of purine/pyrimidine nucleotides between the
      complementary strands or monitoring of amplification of specific DNA fragments in
      a duplex polymerase chain reaction) are demonstrated.

PMID- 18321079
TI  - Efficient identification of phosphorylation by mass spectrometric phosphopeptide
      fingerprinting.
AB  - We describe a rapid and efficient method for the identification of
      phosphopeptides, which we term mass spectrometric (MS) phosphopeptide
      fingerprinting. The method involves quantitative comparison of proteolytic
      peptides from native versus completely dephosphorylated proteins.
      Dephosphorylation of serine, threonine, and tyrosine residues is achieved by in
      gel treatment of the separated proteins with hydrogen fluoride (HF). This
      chemical dephosphorylation results in enrichment of those unmodified peptides
      that correspond to previously phosphorylated peptides. Quantitative comparison of
      the signal-to-noise ratios of peaks in the treated versus untreated samples are
      used to identify phosphopeptides, which can be confirmed and further studied by
      tandem mass spectrometry (MS/MS). We have applied this method to identify eight
      known phosphorylation sites of Xenopus Aurora A kinase, as well as several novel
      sites in the Xenopus chromosome passenger complex (CPC).

PMID- 18321080
TI  - Rotationally resolved IR-diode laser studies of ground-state CO2 excited by
      collisions with vibrationally excited pyridine.
AB  - Relaxation of highly vibrationally excited pyridine (C5NH5) by collisions with
      carbon dioxide has been investigated using diode laser transient absorption
      spectroscopy. Vibrationally hot pyridine (E' = 40,660 cm(-1)) was prepared by 248
      nm excimer laser excitation followed by rapid radiationless relaxation to the
      ground electronic state. Pyridine then collides with CO2, populating the high
      rotational CO2 states with large amounts of translational energy. The CO2 nascent
      rotational population distribution of the high-J (J = 58-80) tail of the 00(0)0
      state was probed at short times following the excimer laser pulse to measure rate
      constants and probabilities for collisions populating these CO2 rotational
      states. Doppler spectroscopy was used to measure the CO2 recoil velocity
      distribution for J = 58-80 of the 00(0)0 state. The energy-transfer distribution
      function, P(E,E'), from E' - E approximately 1300-7000 cm(-1) was obtained by re
      sorting the state-indexed energy-transfer probabilities as a function of DeltaE.
      P(E,E') is fit to an exponential or biexponential function to determine the
      average energy transferred in a single collision between pyridine and CO2. Also
      obtained are fit parameters that can be compared to previously studied systems
      (pyrazine, C6F6, methylpyrazine, and pyrimidine/CO2). Although the rotational and
      translational temperatures that describe pyridine/CO2 energy transfer are similar
      to previous systems, the energy-transfer probabilities are much smaller. P(E,E')
      fit parameters for pyridine/CO2 and the four previously studied systems are
      compared to various donor molecular properties. Finally, P(E,E') is analyzed in
      the context of two models, one indicating that P(E,E') shape is primarily
      determined by the low-frequency out-of-plane donor vibrational modes, and the
      other that indicates that P(E,E') shape can be determined from how the donor
      molecule final density of states changes with DeltaE.

PMID- 18321081
TI  - Femtosecond photolysis of aqueous formamide.
AB  - In this work, we investigate the primary photodynamics of aqueous formamide. The
      formamide was photolyzed using 200 nm femtosecond pulses, and formation of
      products and their relaxation was followed with approximately 300 fs time
      resolution using probe pulses covering the range from 193 to 700 nm. Following
      excitation, the majority of formamide molecules (approximately 80%) converts the
      electronic excitation energy to vibrational excitation, which effectively is
      dissipated to the solvent through vibrational relaxation in just a few
      picoseconds. The vibrational relaxation is observed as a distinct modulation of
      the electronic absorption spectrum of formamide. The relaxation process is
      modeled by a simple one-dimensional wavepacket calculation. A smaller fraction of
      the excited formamide molecules dissociates to the CHO and NH2 radical pairs, of
      which 50% escape recombination. In addition to the electronic excitation of
      formamide, we also observe a small contribution from one-photon ionization of
      formamide and two-photon ionization and dissociation of the water solvent.

PMID- 18321082
TI  - Binding properties of Cu(+/2+)-(glycyl)n glycine complexes (n = 1-3).
AB  - The structure, relative energies, and binding energies of the complexes formed by
      the interaction of Cu+ (d10,1S) and Cu2+ (d9,2D) cations with the (glycyl)n
      glycine (n = 1-3) oligomers have been theoretically determined by means of
      density functional methods. The most stable structures of the Cu+ systems present
      linear dicoordination geometries, in agreement with a recent X-ray absorption
      spectroscopic study of Cu(I) interacting with model dipeptides. This is
      attributed to an efficient reduction of metal-ligand repulsion through sd sigma
      hybridization in dicoordinated linear structures. In contrast, for Cu2+ systems
      the lowest energy structures are tricoordinated (n = 1), tetracoordinated (n =
      2), and pentacoordinated (n = 3). For both copper cations, binding energy values
      show that the interaction energies increase when the peptide chain is elongated.
      Differences on the coordination properties of the ligands are discussed according
      to their length as well as to the electronic configuration of the metal cations,
      which are compared to the Cu+/2+-glycine systems.

PMID- 18321083
TI  - Tautomeric properties and gas-phase structure of 3-chloro-2,4-pentanedione.
AB  - The tautomeric properties of alpha-chlorinated acetylacetone, 3-chloro-2,4
      pentanedione CH3C(O)-CHCl-C(O)CH3, have been investigated by gas electron
      diffraction (GED) and quantum chemical calculations (B3LYP and MP2 approximations
      with different basis sets up to cc-pVTZ). Analysis of the GED intensities
      resulted in the presence of 100(2)% enol tautomer at 269(8) K. The following
      skeletal geometric parameters (rh1 values) of the molecule, which possesses Cs
      symmetry, were derived: r(C=C) = 1.378(3) A, r(C-C) = 1.450(3) A, r(C=O) =
      1.243(3) A, r(C-O) = 1.319(3) A, r(O-H) = 1.001(4) A, r(C-Cl) = 1.752(4) A,
      angleC-C=C = 121.3(1.0) degrees , angleC=C-O = 119.9(1.2) degrees , angleC-C=O =
      119.1(1.2) degrees . Due to very small contributions of the keto tautomer in
      alpha-chlorinated acetylacetone and its parent species, the effect of alpha
      chlorination on tautomeric properties cannot be derived from experimental data.
      Quantum chemical calculations (B3LYP/6-31G**, B3LYP/cc-pVTZ, and MP2/cc-pVTZ)
      predict that alpha-chlorination of acetylacetone has no pronounced effect on the
      tautomeric properties. On the other hand, similar calculations for 1-chloro-1,3
      butanedion, ClC(O)-CH2-C(O)CH3, demonstrate that chlorination in one beta
      position destabilizes the enol tautomer. In both chlorinated species the enol
      form is strongly preferred.

PMID- 18321084
TI  - Ab initio modeling of the electronic circular dichroism induced in porphyrin
      chromophores.
AB  - The optical activity in porphyrins can easily be induced by a chiral environment,
      but it is difficult to determine the underlying mechanisms purely on an
      experimental basis. Therefore, in this study, magnitudes of the perturbational,
      dipolar, and direct covalent contributions to the electronic circular dichroism
      (CD) are evaluated with the aid of quantum chemical computations. Electronic
      properties of model porphyrin chromophores are analyzed. Time-dependent density
      functional theory (TD DFT), particularly with the hybrid B3LYP functional,
      appeared suitable for estimation of the electronic excitation energies and
      spectral intensities. The transition dipole coupling (TDC) between chirally
      stacked porphyrins was determined as the most important mechanism contributing to
      their optical activity. This is in agreement with previous experimental
      observations, where chiral matrices often induce the stacking and large CD
      signals. About a 10 times smaller signal could be achieved by a chiral
      orientation of the phenyl or similar residues covalently attached to the
      porphyrin core. Also, this prediction is in agreement with known experiments.
      Perturbation models realized by a chirally arranged porphyrin and a point charge,
      or by a porphyrin and the methane molecule, provided the smallest CD signals. The
      electrically neutral methane induced similar CD magnitudes as those of the
      charge, but spectral shapes were different. For a complex of porphyrin and the
      alanine cation, a significant influence of the solvent on the resultant CD
      spectral shape was observed, while for the charge and methane perturbations, a
      negligible solvent effect was found. Detailed dependence of the induced optical
      activity on variations of geometrical parameters is discussed. The simulations of
      the induced porphyrin activity can thus bring important information about the
      structure and intermolecular interactions in chiral complexes.

PMID- 18321085
TI  - Near-infrared photoluminescence from a plutonyl ion.
AB  - We report the first example of photoluminescence from electronically excited
      states of the plutonyl ion. Discrete emission transitions were measured between
      6000 and 10,200 cm(-1) from crystalline Cs2U(Pu)O2Cl4 cooled to 75 K following
      pulsed laser excitation at 628 nm. An excitation spectrum in the region of 15,000
      16,500 cm(-1) is compared with 4.2 K plane-polarized absorption spectra reported
      by Gorshkov and Mashirov. Analysis of excited-state lifetime data suggests
      multiple relaxation pathways in the electronic structure of PuO2Cl4(2-).

PMID- 18321086
TI  - Quantum chemistry study on cation structures of fluorinated and chlorinated
      germanes and their radicals.
AB  - The structures and vibrational frequencies of cations of fluorinated and
      chlorinated germanes and radicals (GeHxXy+, X = F, Cl; x + y = 1-4) and
      protonated germanes are investigated theoretically at B3LYP/6-31+G(2df,p) level.
      For GeH2, GeHX, GeH2X, GeHX2, and germanes, the most stable cationic structures
      are largely distorted from their neutral ones and all can be viewed as ion
      complexes between a Ge-centered cation and a neutral atom or diatom. The
      ionization potentials, appearance energies, and proton affinities are obtained at
      Gaussian-3(CC) levels. Cations with the lowest energy (and adiabatic ionization
      potentials (in eV)) are Ge+-H2 (2B2, 8.94), Ge+-FH (9.42), Ge+-ClH (9.45),
      GeH3(+) (8.01), GeF+-H2 (7.71), GeCl+-H2 (8.01), GeF+-FH (7.69), GeCl+-ClH
      (7.80), GeH2(+)-H2 (10.45), GeH2(+)-FH (10.32), GeHF+-FH (10.64), GeF2(+)-FH
      (11.40), GeF4(+) (15.22), GeH2(+)-ClH (10.29), GeHCl+-ClH (10.33), GeCl2(+)-ClH
      (10.43), and GeCl4(+) (11.48). The most stable protonated germanes (and proton
      affinities (in kJ/mol, 0 K)) are GeH3(+)-H2 (658.3), GeH3(+)-FH (672.5), GeH2F+
      FH (634.2), GeHF2(+)-FH (583.4), GeF3(+)-FH (516.3), GeH3(+)-ClH (672.7), GeH2Cl+
      ClH (652.6), GeHCl2(+)-ClH (637.5), and GeCl3(+)-ClH (624.4), respectively. The
      G3 atomization energies of fluorinated Ge-species are found to be significantly
      different from G3X and G4 ones, and this may merit further investigation.

PMID- 18321087
TI  - Development of a new regression analysis method using independent component
      analysis.
AB  - In this paper, independent component analysis (ICA) and regression analysis are
      combined to extract significant components. ICA is a method that extracts
      mutually independent components from explanatory variables. A relationship
      between the independent components and an objective variable is constructed by
      the least-squares method. This method is named ICA-MLR (MLR = multiple linear
      regression). We verified the superiority of ICA-MLR over partial least squares
      (PLS) with simulation data and tried to apply this method to a quantitative
      structure-property relationship analysis of aqueous solubility. We constructed
      models between aqueous solubility and 173 molecular descriptors. PLS and genetic
      algorithm PLS models were constructed for a comparison of ICA-MLR. R2, Q2, and
      Rpred2 values of the PLS model are 0.836, 0.819, and 0.848, respectively. These
      values of the ICA-MLR model are 0.937, 0.868, and 0.894, respectively. ICA-MLR
      achieved higher predictive accuracy than PLS. ICA-MLR could extract effective
      components from explanatory variables and construct the regression model with
      high predictive accuracy. In addition, the information of regression coefficients
      bICA-MLR indicates the magnitude of contribution of each descriptor in the
      analysis of aqueous solubility.

PMID- 18321088
TI  - Diffusion constant of a nonspecifically bound protein undergoing curvilinear
      motion along DNA.
AB  - The mechanism of a protein's diffusion along a DNA segment is a subject of much
      current interest because of the involvement of this diffusion in numerous
      biological processes, including the recognition of DNA sequences and chemical
      modifications of DNA. In this work we present a theoretical derivation of the
      diffusion coefficient of a nonspecifically bound protein, assuming that the
      protein follows a helical track along the DNA. It is shown that, for protein
      sized molecules, the principal contribution to the total translational friction
      comes from the curvilinear motion along the helix, and this contribution is given
      by 6pietaRR(oc)(2) + 8pietaR(3), where R is the protein radius, ROC is the
      distance of separation between the center of mass of the protein and the helical
      axis of DNA, and eta is the viscosity of the medium. The translational diffusion
      of the protein along the helical track of DNA is thus predicted to have a nearly
      R(-3) size dependence, not the R(-1) dependence characterizing simple
      translational diffusion. It is shown that this expression gives rather good
      estimates of the translational diffusion coefficient measured in single molecule
      experiments.

PMID- 18321089
TI  - A multi-frequency pulse EPR and ENDOR approach to study strongly coupled nuclei
      in frozen solutions of high-spin ferric heme proteins.
AB  - In spite of the tremendous progress in the field of pulse electron paramagnetic
      resonance (EPR) in recent years, these techniques have been scarcely used to
      investigate high-spin (HS) ferric heme proteins. Several technical and spin
      system-specific reasons can be identified for this. Additional problems arise
      when no single crystals of the heme protein are available. In this work, we use
      the example of a frozen solution of aquometmyoglobin (metMb) to show how a multi
      frequency pulse EPR approach can overcome these problems. In particular, the
      performance of the following pulse EPR techniques are tested: Davies electron
      nuclear double resonance (ENDOR), hyperfine correlated ENDOR (HYEND), electron
      electron double resonance (ELDOR)-detected NMR, and several variants of hyperfine
      sublevel correlation (HYSCORE) spectroscopy including matched and SMART HYSCORE.
      The pulse EPR experiments are performed at X-, Q- and W-band microwave
      frequencies. The advantages and drawbacks of the different methods are discussed
      in relation to the nuclear interaction that they intend to reveal. The analysis
      of the spectra is supported by several simulation procedures, which are
      discussed. This work focuses on the analysis of the hyperfine and nuclear
      quadrupole tensors of the strongly coupled nuclei of the first coordination
      sphere, namely, the directly coordinating heme and histidine nitrogens and the
      17O nucleus of the distal water ligand. For the latter, 17O-isotope labeling was
      used. The accuracy of our results and the spectral resolution are compared in
      detail to an earlier single-crystal continuous-wave ENDOR study on metMb, and it
      will be shown how additional information can be obtained from the multi-frequency
      approach. The current work is therefore prone to become a template for future
      EPR/ENDOR investigations of HS ferric heme proteins for which no single crystals
      are available.

PMID- 18321090
TI  - Phase behavior and properties of reverse vesicles in salt-free catanionic
      surfactant mixtures.
AB  - Salt-free 1:1 cationic/anionic (catanionic) surfactant mixture
      tetradecyltrimethylammonium laurate (TTAL) could be prepared by mixing equimolar
      tetradecyltrimethylammonium hydroxide (TTAOH) and lauric acid (LA) in water.
      Given the condition of suitable range of weight fraction of TTAL in total
      surfactant, rho=WTTAL/(WTTAL+WLA), and at existence of a small amount of water,
      it was found that the mixtures of so-obtained TTAL and LA could spontaneously
      form stable reverse vesicles in various organic solvents including toluene, tert
      butylbenzene, and cyclohexane. The reverse vesicle phase shows a blue color
      against room light and exhibits strong birefringence under polarized microscope.
      The reverse vesicles are very sensitive to temperature change. Increasing
      temperature could make the rho values within which reverse vesicles were
      constructed move to higher values. In organic solvents of alkanes such as n
      heptane, reverse vesicles could still form but become unstable upon time and
      centrifugation. Increasing temperature could accelerate phase separation, and
      finally a gel-like bottom phase was usually observed. Interestingly, the stable
      reverse vesicles formed by so-called salt-free catanionic surfactant mixtures
      still show some resistance against adding inorganic salts. They can trap
      inorganic ions such as Zn2+ and S2- into their hydrophilic layers. This opens the
      door for template applications of reverse vesicles to prepare inorganic
      nanoparticles.

PMID- 18321091
TI  - Proton conducting ionic liquid organization as probed by NMR: self-diffusion
      coefficients and heteronuclear correlations.
AB  - The structure and local organization of new proton conducting ionic liquids
      (PCILs) obtained by reacting alkylamine with various acids were deciphered by
      complementary 1- and 2-D heteronuclear NMR experiments. One the one hand, PFG NMR
      yielded the self-diffusion coefficients of the PCIL components (and thus
      information on their possible concerted translational motions), while on the
      other hand, 13C, 1H, and 15N, 1H correlation and intermolecular Overhauser
      experiments gave insight into the nature of protonic species and ion-pairing
      behavior.

PMID- 18321093
TI  - Direct asymmetric iodination of aldehydes using an axially chiral bifunctional
      amino alcohol catalyst.
AB  - A direct asymmetric iodination reaction of aldehydes with NIS was found to be
      catalyzed by the novel axially chiral bifunctional amino alcohol (S)-1d. This
      method represents the rare example of the catalytic and highly enantioselective
      synthesis of optically active alpha-iodoaldehydes.

PMID- 18321094
TI  - Influence of redox molecules on the electronic conductance of single-walled
      carbon nanotube field-effect transistors: application to chemical and biological
      sensing.
AB  - In an effort to develop sensitive nanoscale devices for chemical and biological
      sensing, we have examined, using liquid gating, the conductance of semiconducting
      single-walled carbon nanotube-based field-effect transistors (SWCNT-FETs) in the
      presence of redox mediators. As examples, redox couples K3Fe(CN)6/K4Fe(CN)6 and
      K2IrCl6/K3IrCl6 are shown to modulate the SWCNT-FET conductance in part through
      their influence via the electrolyte gate on the electrostatic potential of the
      solution, as described by Larrimore et al. (Nano Lett. 2006, 6, 3129-1333) and in
      part through electron transfer between the redox mediators and the nanotubes. In
      the latter case, the rate of electron transfer is determined by the difference in
      chemical potential between the redox mediator and the SWCNTs and by the
      concentrations of the oxidized and reduced forms of the redox couple.
      Furthermore, these devices can detect the activity of redox enzymes through their
      sensitivity to the change in oxidation state of the enzyme substrate. An example
      is given for the blue copper oxidase, Trametes versicolor laccase, in which the
      rate of change of the SWCNT device conductance is linearly proportional to the
      rate of oxidation of the substrate 10-(2-hydroxyethyl)phenoxazine, varied over 2
      orders of magnitude by the laccase concentration in the picomolar range. The
      behavior described in this work provides a highly sensitive means with which to
      do chemical and biological sensing using SWCNTs that is different from the
      amperometric, capacitive, and field-effect type sensing methods previously
      described in the literature for this material.

PMID- 18321095
TI  - Evidence of water reorientation on model electrocatalytic surfaces from
      nanosecond-laser-pulsed experiments.
AB  - The behavior of water at the interface formed between a quasi-perfect Pt(111)
      single-crystal electrode and an aqueous electrolyte solution is studied by means
      of the laser-induced temperature jump method. This method is based on the use of
      nanosecond laser pulses to suddenly increase the temperature at the interface.
      The measurement of the response of the interface toward the laser heating under
      coulostatic conditions provides evidence on the net orientation of water at the
      interface. Especially interesting is the study of the effect on the interfacial
      water caused by the selective deposition of foreign metal adatoms, because these
      bimetallic systems usually exhibit appealing electrocatalytic properties. The T
      jump methodology shows that the surface composition strongly affects the
      interaction of water with the surface. The most representative parameter to
      characterize this interaction is the potential where water reorientation occurs;
      this potential shifts in different directions, depending on the relative values
      of the electronegativity of the adatom and the substrate. These results are
      discussed in the light of available information about the effect of adatom
      deposition on the work function and the surface potential of the modified
      surface. Finally, some implications on the enhancement of the electrocatalytic
      activity are briefly discussed.

PMID- 18321096
TI  - Arylallylic lithium compounds, internally versus externally coordinated:
      comparison of their structures and dynamic behavior via X-ray crystallography and
      NMR.
AB  - A comparison of externally coordinated arylallyllithiums with internally
      coordinated arylallyllithiums using a combination of X-ray and NMR studies shows
      that 2-bis(2-methoxyethyl)aminomethyl-1-phenylallyllithium 7, and 2-bis(2
      methoxyethyl)aminomethyl-1,3-diphenylallyllithi um 8, are indeed fully internally
      coordinated with all phenyls endo, and lithium is close to one terminal allyl
      carbon. By contrast, among the externally coordinated analogs 1-phenylallyl
      lithium.(HMPT)4 5, and 1-phenylallyllithium.(THF) 6, both phenyls are exo and the
      proximity of lithium to anion was only detected in compound 6. Lithium-7 NMR
      clearly identifies the Li(HMPT)4+ complex in 5, whereas a 7Li{1H} HOESY
      experiment reveals 7Li to be coordinated to THF in 6 and close to the PhC
      terminal allyl carbon. Carbon-13 NMR shows that all of the above compounds are
      fully delocalized despite differences among the sites of lithium and their
      separations from the anions. Changes in the 13C NMR line shapes show that the
      diphenyl compound 8 undergoes a very fast 1,3-lithium sigmatropic shift, and all
      of the phenyls in the above compounds undergo fast rotation around their phenyl
      Cipso-Callyl bonds. Barriers to rotation, DeltaH from NMR line shapes for 5, 6,
      7, and 8 respectively, are 19.8, 14.6, 10.2, and 8.9 kcal x mol-1. The decrease
      in barriers is clearly correlated with a decrease in separation of lithium from
      an allyl terminal carbon and implies that especially among the latter three, 6,
      7, and 8, lithium is involved in the mechanism for phenyl rotation. This question
      is discussed.

PMID- 18321098
TI  - Protein structure determination from 13C spin-diffusion solid-state NMR
      spectroscopy.
AB  - Proton-driven 13C spin diffusion (PDSD) is a simple and robust two-dimensional
      NMR experiment. It leads to spectra with a high signal-to-noise ratio in which
      cross-peaks contain information about internuclear distances. We show that the
      total information content is sufficient to determine the atomic-resolution
      structure of a small protein from a single, uniformly 13C-, 15N-labeled
      microcrystalline sample. For the example of ubiquitin, the structure was
      determined by a manual procedure followed by an automatic optimization of the
      manual structure as well as by a fully automated structure determination
      approach. The relationship between internuclear distances and cross-peak
      intensities in the spectra is investigated.

PMID- 18321097
TI  - Minimal pharmacophoric elements and fragment hopping, an approach directed at
      molecular diversity and isozyme selectivity. Design of selective neuronal nitric
      oxide synthase inhibitors.
AB  - Fragment hopping, a new fragment-based approach for de novo inhibitor design
      focusing on ligand diversity and isozyme selectivity, is described. The core of
      this approach is the derivation of the minimal pharmacophoric element for each
      pharmacophore. Sites for both ligand binding and isozyme selectivity are
      considered in deriving the minimal pharmacophoric elements. Five general-purpose
      libraries are established: the basic fragment library, the bioisostere library,
      the rules for metabolic stability, the toxicophore library, and the side chain
      library. These libraries are employed to generate focused fragment libraries to
      match the minimal pharmacophoric elements for each pharmacophore and then to link
      the fragment to the desired molecule. This method was successfully applied to
      neuronal nitric oxide synthase (nNOS), which is implicated in stroke and
      neurodegenerative diseases. Starting with the nitroarginine-containing dipeptide
      inhibitors we developed previously, a small organic molecule with a totally
      different chemical structure was designed, which showed nanomolar nNOS inhibitory
      potency and more than 1000-fold nNOS selectivity. The crystallographic analysis
      confirms that the small organic molecule with a constrained conformation can
      exactly mimic the mode of action of the dipeptide nNOS inhibitors. Therefore, a
      new peptidomimetic strategy, referred to as fragment hopping, which creates small
      organic molecules that mimic the biological function of peptides by a
      pharmacophore-driven strategy for fragment-based de novo design, has been
      established as a new type of fragment-based inhibitor design. As an open system,
      the newly established approach efficiently incorporates the concept of early
      "ADME/Tox" considerations and provides a basic platform for medicinal chemistry
      driven efforts.

PMID- 18321099
TI  - Guest-induced modification of a magnetically active ultramicroporous, gismondine
      like, copper(II) coordination network.
AB  - A novel ultramicroporous coordination polymer, namely [Cu(F-pymo)2(H2O)1.25]n (1,
      F-pymo = 5-fluoropyrimidin-2-olate), has been prepared and structurally
      characterized. 1 displays a zeolitic gismondine (GIS) topology, with ca. 2.9 A
      wide helical channels which, in the thermally activated counterpart (1'), account
      for a 13% void volume and are responsible for the observed selective solid-gas
      adsorption properties toward H2, N2, and CO2. At 77 K 1' behaves as a molecular
      sieve, selectively adsorbing H2 over N2, possibly due to size-exclusion reasons.
      At variance, although CO2 molecules are slightly larger than the pore size, they
      are readily incorporated by 1' at temperatures as high as 433 K. Variable
      temperature X-ray powder diffraction (TXRPD) studies, in the temperature range
      303-473 K, show that dehydration is reversible and has almost negligible effects
      on the network. At variance, the uptake of CO2 occurs through a transient phase
      and channels expansion. While the gas storage capacity of 1' is not very high-H2,
      0.56 wt % and 0.010 kg H2/L at 90 K and 900 Torr, and CO2, 7.6 wt % at 273 K and
      900 Torr-the guest molecules achieve very high densities, comparable to that of
      the liquid for H2 (0.023 vs 0.021 molecules A-3) and to that of the solid for CO2
      (0.014 vs 0.022 molecules A-3). In addition, we have also studied the effect of
      the perturbation exerted by the guest molecules on its magnetic properties. The
      results show that while dehydration of 1 has negligible effect on its spin-canted
      antiferromagnetic behavior, CO2 incorporation in the pores is responsible for an
      increment of the transition temperature at which the weak ferromagnetic ordering
      takes place from 22 to 29 K.

PMID- 18321100
TI  - One-dimensional iron-cyclopentadienyl sandwich molecular wire with half metallic,
      negative differential resistance and high-spin filter efficiency properties.
AB  - We present a theoretical study on a series of novel organometallic sandwich
      molecular wires (SMWs), which are constructed with alternating iron atoms and
      cyclopentadienyl (Cp) rings, using DFT and nonequilibrium Green's function
      techniques. It is found that that the SMWs are stable, flexible structures having
      half-metallic (HM) properties with 100% negative spin polarization near the Fermi
      level in the ground state. Some SMWs of finite size show a nearly perfect spin
      filter effect (SFE) when coupled between ferromagnetic electrodes. Moreover,
      their I-V curves exhibit negative differential resistance (NDR), which is
      essential for certain electronic applications. The SMWs are the first linear
      molecules with HM, high SFE, and NDR and can be easily synthesized. In addition,
      we also analyze the underlying mechanisms via the transmission spectra and spin
      dependent calculations. These findings strongly suggest that the SMWs are
      promising materials for application in molecular electronics.

PMID- 18321101
TI  - Genetically encoding protein oxidative damage.
AB  - Posttranslational modification of tyrosine residues in proteins, to produce 3
      nitrotyrosine (3-NT), is associated with over 50 disease states including
      transplant rejection, lung infection, central nervous system and ocular
      inflammation shock, cancer, and neurological disorders (for example, Alzheimer's
      disease, Parkinson's disease, and stroke). The levels of 3-NT increase in aging
      tissue, and levels of 3-NT in proteins are a predictor of disease risk. Here we
      report the evolution and characterization of an aminoacyl-tRNA synthetase/tRNA
      pair for the cotranslational, site-specific incorporation of 3-NT into proteins
      at genetically encoded sites. To demonstrate the utility of our approach for
      studying the effect on protein function of nitration on sites defined in vivo, we
      prepared manganese superoxide dismutase (MnSOD) that is homogeneously nitrated at
      a site known to be modified in disease-related inflammatory responses, and we
      measured the effect of this defined modification on protein function.

PMID- 18321102
TI  - Palladium(II)-catalyzed direct arylation of enaminones using
      organotrifluoroborates.
AB  - A Pd(II)-catalyzed reaction for the direct arylation of cyclic enaminones is
      reported. The reactivity of electron-rich, electron-poor, and sterically
      encumbered organotrifluoroborates was investigated. This reaction represents a
      unique use for organotrifluoroborates as coupling partners and discloses the
      utility of enaminones for direct-functionalization reactions. It provides
      immediate access to arylpiperidine, indolizidine, and quinolizidine scaffolds
      from the corresponding mono- and bicyclic, unattenuated enaminones.

PMID- 18321103
TI  - Selective detection of vapor phase hydrogen peroxide with phthalocyanine
      chemiresistors.
AB  - The use of hydrogen peroxide as a precursor to improvised explosives has made its
      detection a topic of critical importance. Chemiresistor arrays comprised of 50 nm
      thick films of metallophthalocyanines (MPcs) are redox selective vapor sensors of
      hydrogen peroxide. Hydrogen peroxide is shown to decrease currents in cobalt
      phthalocyanine sensors while it increases currents in nickel, copper, and metal
      free phthalocyanine sensors; oxidation and reduction of hydrogen peroxide via
      catalysis at the phthalocyanine surface are consistent with the pattern of sensor
      responses. This represents the first example of MPc vapor sensors being oxidized
      and reduced by the same analyte by varying the metal center. Consequently,
      differential analysis by redox contrast with catalytic amplification using a
      small array of sensors may be used to uniquely identify peroxide vapors.
      Metallophthalocyanine chemiresistors represent an improvement over existing
      peroxide vapor detection technologies in durability and selectivity in a greatly
      decreased package size.

PMID- 18321104
TI  - Generation and spectroscopic characterization of ruthenacyclobutane and ruthenium
      olefin carbene intermediates relevant to ring closing metathesis catalysis.
AB  - The reaction of phosphonium alkylidenes [(H2IMes)RuCl2=CHPR3]+[A]- (R = C6H11, A
      = OTf or B(C6F5)4, 1-Cy; R = i-C3H7, A = ClB(C6F5)3 or OTf, 1-iPr) with 1 equiv
      of ethylene at -78 degrees C, in the presence of 2-3 equiv of a trapping olefin
      substrate, yields intermediates relevant to olefin metathesis catalytic cycles.
      Dimethyl cyclopent-3-ene-1,1-dicarboxylate gives solutions of a substituted
      ruthenacyclobutane 3 of relevance to ring closing metathesis catalysis. 1H and
      13C NMR data are fully consistent with its assignment as a ruthenacyclobutane,
      but 1JCC values of 23 Hz for the CalphaH2-Cbeta bond and 8.5 Hz for the CalphaH
      Cbeta bond point to an unsymmetrical structure in which the latter bond is more
      activated than the former. In contrast, trapping with acenaphthylene leads to an
      olefin carbene complex (6) in which the putative ruthenacyclobutane has opened;
      this species was also fully characterized by NMR spectroscopy and compared to
      related species reported previously.

PMID- 18321105
TI  - Syntheses of highly fluorescent GFP-chromophore analogues.
AB  - Eight B-containing compounds, i.e., 1a-h, were prepared as mimics of the green
      fluorescent protein (GFP) fluorophore. The underlying concept was that synthetic
      GFP chromophore analogues are not fluorescent primarily because of free rotation
      about an aryl-alkene bond (Figure 1b). This rotation is not possible in the beta
      barrel of GFP; hence, the molecule is strongly fluorescent. In compounds 1a-h,
      radiationless decay via this mechanism is prevented by complexation of the BF2
      entity. The target materials were prepared via two methods; most were obtained
      according to the novel route shown in Scheme 1b, but compound 1f was made via the
      procedure described in Scheme 2. Both syntheses involved formation of undesired
      compounds E-4a-h that formed simultaneously with the desired isomeric
      intermediates Z-4a-h. Both compounds form BF2 adducts, i.e., 1a-h and 5a-h,
      respectively. Methods used for spectroscopic characterization and differentiation
      of compounds in the series 1 and 5 are discussed, and these are supported by
      single-crystal X-ray diffraction analyses for compounds 1c, 5c, 1f, and 5f.
      Electronic spectra of compounds 1a-h and 5a-h were studied in detail. Those in
      the 5 series were shown to be only weakly fluorescent, but the 1 series were
      strongly fluorescent compounds (comparable to the boraindacene, BODIPY, dyes).
      Compounds 1g and 1h are water soluble, and 1h has particularly significant
      potential as a probe, since it also has a carboxylic acid group for attachment to
      biomolecules.

PMID- 18321106
TI  - Emissive terbium probe for multiphoton in vitro cell imaging.
AB  - A polymeric terbium complex that can be excited by near-infrared excitation at
      800 nm via multiphoton absorption processes has been synthesized. This complex
      has been demonstrated to show strong, observable, three-photon-induced f-f
      emission in cell imaging. In vitro studies carried out in three carcinoma cell
      lines (A549, HONE1, and HeLa) have been performed and shown to have low
      cytotoxicity. This complex is therefore a potential candidate for future infrared
      excitation imaging dyes.

PMID- 18321107
TI  - Controlling a single protein in a nanopore through electrostatic traps.
AB  - Protein-protein pore interaction is a fundamental and ubiquitous process in
      biology and medical biotechnology. Here, we employed high-resolution time
      resolved single-channel electrical recording along with protein engineering to
      examine a protein-protein pore interaction at single-molecule resolution. The
      pore was formed by Staphylococcus aureus alpha-hemolysin (alphaHL) protein and
      contained electrostatic traps formed by rings of seven aspartic acid residues
      placed at two different positions within the pore lumen. The protein analytes
      were positively charged presequences (pb2) of varying length fused to the small
      ribonuclease barnase (Ba). The presence of the electrostatic traps greatly
      enhanced the interaction of the pb2-Ba protein with the alphaHL protein pore.
      This study demonstrates the high sensitivity of the nanopore technique to an
      array of factors that govern the protein-protein pore interaction, including the
      length of the pb2 presequence, the position of the electrostatic traps within the
      pore lumen, the ionic strength of the aqueous phase, and the transmembrane
      potential. Alterations in the functional properties of the pb2-Ba protein and the
      alphaHL protein pore and systematic changes of the experimental parameters
      revealed the balance between forces driving the pb2-Ba protein into the pore and
      forces driving it out.

PMID- 18321108
TI  - Templation of the excited-state chemistry of alpha-(n-alkyl) dibenzyl ketones:
      how guest packing within a nanoscale supramolecular capsule influences
      photochemistry.
AB  - Excited-state behavior of eight alpha-alkyl dibenzyl ketones (alkyl = CH3 through
      n-C8H17) that are capable of undergoing type II and/or type I photoreactions has
      been explored in isotropic solution and within a water-soluble capsule. The study
      consisted of two parts: photochemistry that explored the excited-state chemistry
      and an NMR analysis that revealed the packing of each guest within the capsule.
      The NMR data (COSY, NOESY, and TOCSY experiments) revealed that ternary complexes
      between alpha-alkyl dibenzyl ketones and the capsule formed by two cavitands are
      kinetically stable, and the guests fall into three packing motifs modulated by
      the length of the alpha-alkyl chain. In essence, the host is acting as an
      external template to promote the formation of distinct guest conformers. The
      major products from all eight guests upon irradiation either in hexane or in
      buffer solution resulted from the well-known Norrish type I reaction. However,
      within the capsule the excited-state chemistry of the eight ketones was dependent
      on the alkyl chain length. The first group consisted of alpha-hexyl, alpha
      heptyl, and alpha-octyl dibenzyl ketones that yielded large amounts of Norrish
      type II products within the host, while in solution the major products were from
      Norrish type I reaction. The second group consists of alpha-butyl and alpha
      pentyl dibenzyl ketones that yield equimolar amounts of two rearranged starting
      ketones within the capsule (combined yield of ca 60%), while in solution no such
      products were formed. The third group consisted of alpha-methyl, alpha-ethyl, and
      alpha-propyl dibenzyl ketones that within the capsule yielded only one (not two)
      rearranged starting ketone in larger amounts (21-35%) while in solution no
      rearrangement product was obtained. Variation in the photochemistry of the guest
      within the capsule, with respect to the alpha-alkyl chain length of the guest,
      highlights the importance of how a small variation in supramolecular structure
      can influence the selectivity within a confined nanoscale reactor.

PMID- 18321109
TI  - N-heterocyclic carbene complexes of Rh: reaction with dioxygen without oxidation.
AB  - The reaction of oxygen with rhodium complexes containing N-heterocyclic carbenes
      was found to give dioxygen complexes with rare square planar geometries and
      unusually short O-O bond lengths. Analysis of the bonding in these complexes by
      Rh L-edge X-ray absorption spectroscopy (XAS), Raman spectroscopy, and DFT
      calculations provides evidence for a bonding model in which singlet oxygen is
      bound to a Rh(I) d8 metal complex, rather than the more common Rh(III) d6 peroxo
      species with octahedral geometry and O-O bond lengths in the 1.4-1.5 A range.

PMID- 18321110
TI  - Fluorenes and styrenes by Au(I)-catalyzed annulation of enynes and alkynes.
AB  - Intermolecular annulation of enynes and propargyl esters to selectively produce
      styrenes or fluorenes is reported. The divergent arene syntheses involve a Au
      catalyzed, two-pot, multistep process proceeding by cis-diastereoselective
      cyclopropanation, cycloisomerization, and, finally, annulation or elimination.

PMID- 18321111
TI  - Reversible loading and unloading of nanoparticles in "exponentially" growing
      polyelectrolyte LBL films.
AB  - The exponentially growing layer-by-layer (LBL) films made from
      poly(diallyldimethylammonium chloride) (PDDA) and poly(acrylic acid) (PAA) were
      used to load and unload the CdTe nanoparticles (NPs). The reversible loading of
      NPs were investigated through UV-vis studies and further confirmed by confocal
      microscopy. In addition the LBL films were also compared for the release kinetics
      for pH 9 and 7 and films capped with (PDDA-PSS)10 layers. The amount of released
      particles at pH 9 was found to be at least 2 orders of magnitude higher than
      those at pH 7 and with (PDDA-PSS)10 capped layers after 25 h. This variation in
      film response for CdTe-particle release presents a route for studies in which
      highly swollen exponentially growing LBL films can be loaded with functionalized
      NPs for biological applications and explored as carriers to hold the NPs inside
      the films for self-assembly.

PMID- 18321112
TI  - Imparting nanoparticle function with size-controlled amphiphilic polymers.
AB  - Herein we report our method of water solubilization and subsequent
      functionalization of a variety of nanoparticle systems with amphiphilic polymers
      containing build-in "chemical handles". We have used these polymers, which have
      narrow polydispersity indices, to impart water solubility and chemical
      sensitivity toward targeted species (here: pH). These material systems have high
      chemical conjugation efficiencies in aqueous conditions which may be used to
      create a variety of chemical and biological multifunctional materials.

PMID- 18321113
TI  - Biocomputing security system: concatenated enzyme-based logic gates operating as
      a biomolecular keypad lock.
AB  - A biomolecular security system mimicking a keypad lock device was developed using
      enzyme-based concatenated AND logic gates resulting in the implication logic
      network.

PMID- 18321114
TI  - A photochemical synthesis of functionalized trans-cyclooctenes driven by metal
      complexation.
AB  - Described is a scalable procedure for driving photochemical sytheses of trans
      cyclooctene derivatives through metal complexation. During photoirradiation,
      reaction mixtures are continuously pumped through a column of a AgNO3-impregnated
      silica gel. The trans-cyclooctene derivative is selectively retained by the AgNO3
      impregnated silica, but the cis-isomer elutes from the column back to the
      reaction flask, where it is photoisomerized and recirculated through the column.
      The method provides access to a range of usefully functionalized derivatives of
      trans-cyclooctene, including a derivative of 5-aza-trans-cyclooctene that
      underwent transannular cyclization upon treatment with bromine. The alkene
      stereochemistry is transferred with high fidelity to the hexahydropyrrolizine
      framework in the transannular cyclization.

PMID- 18321115
TI  - TOF-2: a large 1D channel thorium organic framework.
AB  - A new neutral 1D channel thorium organic framework material (TOF-2) has been
      synthesized under hydrothermal conditions. TOF-2 exhibits a hexagonal channel
      structure consisting of eight-coordinate ThO6F2 polyhedra and 1,3,5
      benzentricarboxylate ligands. The channels run along the c-axis and are
      approximately 13 A in diameter. The single-crystal X-ray structure suggests that
      the amount of void space is 41%. The structure is stable to ca. 400 degrees C.
      Gas adsorption measurements show deferential gas uptake behavior.

PMID- 18321116
TI  - Crystal structure of the gold nanoparticle [N(C8H17)4][Au25(SCH2CH2Ph)18].
AB  - We report the crystal structure of the thiolate gold nanoparticle
      [TOA+][Au25(SCH2CH2Ph)18-], where TOA+ = N(C8H17)4+. The crystal structure
      reveals three types of gold atoms: (a) one central gold atom whose coordination
      number is 12 (12 bonds to gold atoms); (b) 12 gold atoms that form the vertices
      of an icosahedron around the central atom, whose coordination number is 6 (five
      bonds to gold atoms and one to a sulfur atom), and (c) 12 gold atoms that are
      stellated on 12 of the 20 faces of the Au13 icosahedron. The arrangement of the
      latter gold atoms may be influenced by aurophilic bonding. Together they form six
      orthogonal semirings, or staples, of -Au2(SCH2CH2Ph)3- in an octahedral
      arrangement around the Au13 core.

PMID- 18321117
TI  - On the structure of thiolate-protected Au25.
AB  - Density functional theory is used to explore the structure of Au25(RS)18. The
      preferred structure consists of an icosahedral Au13 core protected by 6 RS-Au-RS
      Au-RS units. The enhanced stability of the structure as an anion is found to
      originate from closure of an eight-electron shell for delocalized Au(6s)
      electrons. The evaluated XRD pattern and optical spectra are in good agreement
      with experimental data.

PMID- 18321118
TI  - Lewis acid promoted carbon-carbon bond cleavage of gamma-silyloxy-beta-hydroxy
      alpha-diazoesters.
AB  - Cyclic gamma-silyloxy-beta-hydroxy-alpha-diazoesters undergo efficient rupture of
      the Cbeta-Cgamma bond when treated with tin tetrachloride to provide tethered
      aldehyde ynoate products in high yield.

PMID- 18321119
TI  - Palladium-catalyzed alpha-arylation of oxindoles.
AB  - A catalyst generated from Pd(dba)2 and the bulky electron-rich phosphine ligand 2
      (dicyclohexylphosphino)-2',4', 6'-tri-i-propyl-1-1'-biphenyl is effective for the
      alpha-arylation of oxindoles. Generation of the potassium-enolates of a range of
      oxindoles allows coupling with aryl chlorides, bromides, and triflates.
      Significant variation of the substitution pattern on both the oxindole and aryl
      halide is possible.

PMID- 18321120
TI  - Long-chain 2H-azirines with heterogeneous terminal halogenation from the marine
      sponge Dysidea fragilis.
AB  - Three new omega-halogenated long-chain 2H-azirines were isolated from the sponge
      Dysidea fragilis. Their structures revealed heterogeneity in both the composition
      of the terminal 1,1-dihalo-vinyl group and enantiomeric ratios at C2 of the
      azirine-2-carboxylate ester terminus. Azirine-2-carboxylate esters were shown to
      racemize spontaneously. A hypothesis is proposed for the biosynthesis of the
      azirinecarboxylate family of natural products that involves enzyme-catalyzed free
      radical halogenation followed by elimination of hydrohalic acid.

PMID- 18321121
TI  - Zeolite NaY-promoted cyclization of farnesal: a short route to nanaimoal.
AB  - The sesquiterpene nanaimoal was synthesized in 21% overall yield and in a
      biomimetic manner. As a key step, the acid-catalyzed cyclization of farnesal
      under zeolite NaY confinement conditions was used. The intrazeolite cyclization
      of farnesal affords as major product a double-bond isomer of nanaimoal, via a
      novel diastereoselective tandem 1,5-diene cyclization/Prins-type reaction.

PMID- 18321122
TI  - Synthesis of fused 4,5-disubstituted indole ring systems by intramolecular
      friedel-crafts acylation of 4-substituted indoles.
AB  - 4-Substituted indoles containing a variety of electrophiles and N-substituents
      undergo Friedel-Crafts acylation to give exclusively the products of cyclization
      at the 5-position of indole. These indanones and tetralones have been scarcely
      prepared and are subunits in natural products and analogues of potential
      biological significance.

PMID- 18321123
TI  - Concise preparation of 2,2-difluorohomopropargyl carbonyl derivatives.
      Application to the synthesis of 4,4-difluoroisoquinolinone congeners.
AB  - A scalable synthesis of 2,2-difluorohomopropargyl esters was achieved using a
      magnesium-promoted Barbier reaction of substituted difluoropropargyl bromides
      with alkyl chloroformates. These 2,2-difluorohomopropargyl esters were effective
      precursors in the synthesis of homopropargylic amides-by aminolysis using AlMe3,
      as well as of ketones-through the reaction of the corresponding Weinreb amides
      with Grignard reagents. Ring closing metathesis using difluorinated 1,7-enyne
      carbonyl compounds furnished six-membered diene products, which were used as
      susbstrates in a Diels-Alder reaction to afford 4,4-difluoroisoquinolin-3-ones.
      The [2 + 2 + 2] cycloaddition of alkynes with fluorinated 1,7-diyne amides gave
      4,4-difluoro-1,4-dihydro-3(2H)-isoquinolinone derivatives regioselectively.

PMID- 18321124
TI  - Morpholine-based immonium and halogenoamidinium salts as coupling reagents in
      Peptide synthesis1.
AB  - Here we describe a new family of N-form immonium-type coupling reagents that
      differ in their carbocation skeleton structure. The N-methylpiperazine derivative
      failed to form immonium salts, while the thiomorpholine derivative did not give
      better results than the coupling reagents currently used. The presence of the
      morpholine had a marked influence on the solubility and stability as well as the
      reactivity of the reagent. Finally, the fluoroamidinium salt performed extremely
      well in the presence of only 1 equiv of base, thereby confirming the effect of
      the proton acceptor in the reaction.

PMID- 18321125
TI  - Synthesis of 2(3H)-furanones via electrophilic cyclization.
AB  - A variety of highly substituted 2(3H)-furanones are readily prepared from 3
      alkynoate esters and the corresponding acids via electrophilic cyclization.
      Successful electrophiles in this process include I2, ICl, and PhSeCl. This highly
      efficient process proceeds under mild conditions, tolerates various functional
      groups, and generally provides substituted 2(3H)-furanones in good to excellent
      yields.

PMID- 18321126
TI  - A C78 fullerene precursor: toward the direct synthesis of higher fullerenes.
AB  - A C78 fullerene related structure (of C78:1 and C78:4, the last undiscovered C78
      IPR isomer) has been synthesized and investigated as a pyrolytic precursor. The
      pyrolysis of precursor containing all 78 carbon atoms in the required positions
      and 93 of the 117 C-C bonds, needed for fullerene formation, showed selectivity
      for C78 fullerene formation. In independent experiments it has been shown that
      the flash pyrolysis of C78 fullerene is not affected by Stone-Wales rearrangement
      and loss of C2 fragments and, thus, is very promising for the synthesis of
      individual isomers of higher fullerenes.

PMID- 18321127
TI  - Probing the efficiency of N-heterocyclic carbene promoted O- to C-carboxyl
      transfer of oxazolyl carbonates.
AB  - Screening of a range of azolium salts, bases and solvents for reactivity
      indicates that triazolinylidenes, generated in situ with KHMDS in THF, promote
      the Steglich rearrangement of oxazolyl carbonates with high catalytic efficiency
      (typical reaction time 5 min at <1.5 mol % NHC). This protocol shows wide
      substrate applicability, even allowing the efficient generation of vicinal
      quaternary centers. An improved experimental procedure is also described that
      allows a simplified one-pot reaction protocol to be employed with similarly high
      catalytic efficiency.

PMID- 18321128
TI  - Anthracene cycloadducts as highly selective chiral auxiliaries.
AB  - A new chiral auxiliary was designed and easily prepared from a Diels-Alder
      cycloadduct of an enantiomerically pure anthracene with maleimide. Excellent
      diastereoselectivities in Diels-Alder reactions, conjugate additions, and aldol
      reactions employing these auxiliaries are now reported.

PMID- 18321129
TI  - Molecular dynamics study of chiral recognition for the whelk-O1 chiral stationary
      phase.
AB  - In this article, we examine the docking of 10 analytes on the Whelk-O1 stationary
      phase. A proper representation of analyte flexibility is essential in the docking
      analysis, and analyte force fields have been developed from a series of B3LYP
      calculations. Molecular dynamics simulations of a representative Whelk-O1
      interface, in the presence of racemic analyte and solvent, form the basis of the
      analysis of chiral selectivity. The most probable docking arrangements are
      identified, the energy changes upon docking are evaluated, and separation factors
      are predicted. From comparisons between the analytes, the mechanism of chiral
      selectivity is divided into contributions from hydrogen bonding, ring-ring
      interactions, steric hindrance, and molecular flexibility. We find that both
      hydrogen bonding and ring-ring interactions are necessary to localize the analyte
      within the Whelk-O1 cleft region. We also identify one docking mechanism that is
      often dominant and analyze the conditions that lead to alternate docking modes.

PMID- 18321130
TI  - Chemical separations by bubble-assisted interphase mass-transfer.
AB  - We show that when a small amount of heat is added close to a liquid-vapor
      interface of a captive gas bubble in a microchannel, interphase mass-transfer
      through the bubble can occur in a controlled manner with only a slight change in
      the temperature of the fluid. We demonstrate that this method, which we refer to
      as bubble-assisted interphase mass-transfer (BAIM), can be applied to interphase
      chemical separations, e.g., simple distillation, without the need for high
      temperatures, vacuum, or active cooling. Although any source of localized heating
      could be used, we illustrate BAIM with an all-optical technique that makes use of
      the plasmon resonance in an array of nanoscale metal structures that are
      incorporated into the channel to produce localized heating of the fluid when
      illuminated by a stationary low-power laser.

PMID- 18321131
TI  - Electron permeable self-assembled monolayers of dithiolated aromatic scaffolds on
      gold for biosensor applications.
AB  - Self-assembled monolayers (SAMs) of thiolated compounds are formed by the
      spontaneous chemisorption of thiolate groups on metal surfaces. In biosensors,
      they are most commonly used to covalently immobilize a biorecognition molecule
      onto the surface of the transducer, thus offering the possibility of controlling
      the orientation, distribution, and spacing of the sensing element while reducing
      nonspecific interactions. In this paper, self-assembled monolayers of dithiolated
      derivatives of 3,5-dihydroxybenzyl alcohol containing carboxyl and hydroxyl end
      groups have been prepared on gold surfaces and characterized by cyclic
      voltammetry and electrochemical impedance spectroscopy. Impedance measurements
      revealed that SAM formation is essentially completed after 3-5 h of exposure by
      observing the successive blocking of the faradic response of ferricyanide anion
      due to the adsorption of the dithiol molecules. The surface coverage of these
      molecules, estimated by reductive desorption experiments, was in the range of
      (1.1-2.8) x 10-10 mol/cm2. To demonstrate the potential of the dithiol SAM, a
      model system for detection of a tumor marker, prostate-specific antigen (PSA),
      was developed. The carboxyl groups of the SAM were succinimide-activated, and an
      anti-PSA antibody was covalently immobilized via amide bonds. The modified SAM
      was used for the label-free detection of prostate-specific antigen using EIS with
      a detection limit of 9 ng/mL. The results described here demonstrate that this
      kind of dithiol-modified SAM can be used as supports in electrochemical
      biosensors and the results are explained in terms of the structural features of
      these dithiols.

PMID- 18321132
TI  - Enhanced protein digestion through the confinement of nanozeolite-assembled
      microchip reactors.
AB  - An on-chip microreactor was proposed toward the acceleration of protein digestion
      through the construction of a nanozeolite-assembled network. The nanozeolite
      microstructure was assembled using a layer-by-layer technique based on
      poly(diallyldimethylammonium chloride) and zeolite nanocrystals. The adsorption
      of trypsin in the nanozeolite network was theoretically studied based on the
      Langmuir adsorption isotherm model. It was found that the controlled trypsin
      containing nanozeolite networks assembled within a microchannel could act as a
      stationary phase with a large surface-to-volume ratio for the highly efficient
      proteolysis of both proteins at low levels and with complex extracts. The maximum
      proteolytic rate of the adsorbed trypsin was measured to be 350 mM min-1 microg
      1, much faster than that in solution. Moreover, due the large surface-to-volume
      ratio and biocompatible microenvironment provided by the nanozeolite-assembled
      films as well as the microfluidic confinement effect, the low-level proteins down
      to 16 fmol per analysis were confidently identified using the as-prepared
      microreactor within a very short residence time coupled to matrix-assisted laser
      desorption-time-of-flight mass spectrometry. The on-chip approach was further
      demonstrated in the identification of the complex extracts from mouse macrophages
      integrated with two-dimensional liquid chromatography-electrospray ionization
      tandem mass spectrometry. This microchip reactor is promising for the development
      of a facile means for protein identification.

PMID- 18321133
TI  - Nanofluidic devices and their applications.
AB  - Recent developments in micro- and nanotechnologies made possible the fabrication
      of devices integrating a deterministic network of nanochannels, i.e., with at
      least one dimension in a range from 1 to 100 nm. The proximity of this dimension
      and the Debye length, the size of biomolecules such as DNA or proteins, or even
      the slip length, added to the excellent control on the geometry gives unique
      features to nanofluidic devices. This new class of devices not only finds
      applications wherever less well-defined porous media, such as electrophoresis
      gels, have been traditionally used but also give a new insight into the sieving
      mechanisms of biomolecules and the fluid flow at the nanoscale. Beyond this, the
      control on the geometry allows smarter design resulting, among others, in new
      separation principles by taking advantage of the anisotropy. This perspective
      gives an overview on the fabrication technologies of nanofluidic devices and
      their applications. In the first part, the current state of the art of
      nanofluidic fabrication is presented. The second part first discusses the key
      transport phenomena in nanochannels. Current applications of nanofluidic devices
      are next discussed. Finally, future challenges and possible applications are
      highlighted.

PMID- 18321134
TI  - Charge monitoring cell mass spectrometry.
AB  - An instrument to directly measure the charge carried by a cell or a microparticle
      as well as mass-to-charge ratio of the cell/microparticle was developed for rapid
      mass distribution measurement. A successful mass spectrum with a record high mass
      has been demonstrated. In this article, the details of the construction and
      operation of the charge monitoring cell mass spectrometer are reported. Examples
      are also given for demonstration and discussion.

PMID- 18321135
TI  - One-step sampling, extraction, and storage protocol for peptidomics using
      dihydroxybenzoic Acid.
AB  - The isolation and extraction of natively occurring signaling peptides (SPs) from
      tissue is a critical first step in characterizing these peptides. Recent studies
      have outlined several approaches designed to preserve and extract SPs from
      tissue. Here, we demonstrate a surprisingly simple method to extract SPs from
      tissue samples, ranging from cell clusters to brain punches to intact brain
      regions, using a matrix often employed in matrix-assisted laser
      desorption/ionization mass spectrometry-2,5-dihydroxybenzoic acid (DHB). DHB
      allows for the effective extraction of endogenous peptides from tissue as well as
      long-term preservation of tissue samples and extracts. Using the mouse pituitary
      gland as a model, the extraction protocol effectively recovers 24 known and many
      additional putative peptides from individual samples. Peptide extracts stored in
      the DHB extraction media are stable for years without freezing. The approach is
      also effective for other neuronal tissues; the complement of neuropeptides in bag
      cell neuron clusters from the Aplysia central nervous system, the rat cerebellum,
      and rat dorsal striatum also have been examined. Advantages of this new
      extraction procedure are its technical simplicity, reproducibility, ease of
      remote preparation of samples, and long-term sample preservation without
      freezing.

PMID- 18321136
TI  - Assessment of the three-dimensional structure of recombinant protein therapeutics
      by NMR fingerprinting: demonstration on recombinant human granulocyte macrophage
      colony stimulation factor.
AB  - We describe a simple, powerful, and robust NMR-based method that has the
      potential to greatly impact the characterization of recombinant protein
      therapeutics. The method ascertains the bioactive conformational identity of
      recombinant human granulocyte macrophage-colony stimulation factor (rhGM-CSF)
      produced in Streptomyces lividans versus Escherichia coli by overlaying their 2D
      1H,15N HSQC correlation spectra. An identical match of all resonances implies
      that rhGM-CSF from both processes share indistinguishable conformations that
      correlate with in vitro activity. The result of this method is unique among
      existing methods. It can detect and quantify the active ingredient. Moreover it
      provides a complete assessment of the conformation with high sensitivity to minor
      structural changes.

PMID- 18321137
TI  - Nucleic acid beacons for long-term real-time intracellular monitoring.
AB  - Real time intracellular monitoring of biological molecules inside living cells is
      important in many biomedical studies and reveals valuable information
      unobtainable by conventional molecular biology techniques. A variety of methods
      and molecular probes have been developed, but long term (from a few hours to
      days) intracellular monitoring with high sensitivity and selectivity is
      impossible and has not been accomplished. We have used locked nucleic acids (LNA)
      to engineer novel molecular beacons (MBs) for long-term intracellular monitoring.
      The LNA-MBs were made of a mixed LNA and DNA bases to have extremely high
      biostability. The new beacons were tested with MDA-MB-231 cancer cells and used
      effectively to monitor mRNA expression levels in real-time for 5-24 h. After 24 h
      inside living cells, the LNA-MBs were still functional, demonstrating a greatly
      enhanced stability enabling the measurement of intracellular gene expression over
      an extended period of time.

PMID- 18321138
TI  - Comment on "Preparation of superparamagnetic ribonuclease a surface-imprinted
      submicrometer particles for protein recognition in aqueous media".

PMID- 18321139
TI  - Micellization of PEO/PS block copolymers at the air/water interface: a simple
      model for predicting the size and aggregation number of circular surface
      micelles.
AB  - Isotherms of monolayers of poly(ethylene oxide) (PEO) and polystyrene (PS)
      triblock copolymers spread at the air/water interface were obtained by film
      balance technique. In a low concentration regime, the PEO segments surrounding
      the PS cores behave the same way as in monolayers of PEO homopolymers. Langmuir
      Blodgett (LB) films prepared by transferring the monolayers onto mica at various
      surface pressures were analyzed by atomic force microscopy (AFM). The results
      reveal that these block copolymers form micelles at the air/water interface.
      Within the micelles, the PS blocks act as anchoring structures at the interface.
      In several cases, aggregation patterns were modified by the dewetting processes
      that occur in Langmuir-Blodgett films transferred to solid substrates. High
      transfer surface pressures and metastable states favored these changes in
      morphology. A flowerlike surface micelle model is proposed to explain the
      organization of the surface circular micelles. The model can be generalized and
      applied to diblock copolymers as well. The model permits prediction of the
      aggregation number and the size of circular surface micelles formed by PEO/PS
      block copolymers at the air/water interface.

PMID- 18321140
TI  - Core-shell-corona micelles by PS-b-P2VP-b-PEO copolymers: focus on the water
      induced micellization process.
AB  - It is now well established that amphiphilic PS-b-P2VP-b-PEO linear triblock
      copolymers can form multilayered assemblies, thus core-shell-corona (CSC)
      micelles, in water. Micellization is triggered by addition of a small amount of
      water into a dilute solution of the PS-b-P2VP-b-PEO copolymer in a non-selective
      organic solvent. However, the phenomena that take place at the very beginning of
      this process are poorly documented. How these copolymer chains are perturbed by
      addition of water was investigated in this work by light and neutron scattering
      techniques and transmission electron microscopy. It was accordingly possible to
      determine the critical water concentration (CWC), the compactness of the nano
      objects in solution, their number of aggregation, and their hydrodynamic diameter
      at each step of the micellization process.

PMID- 18321141
TI  - Electrostatic self-organization of robust porphyrin-polyoxometalate films.
AB  - Strategies to create thin films using layer-by-layer methods use oppositely
      charged polymeric polyelectrolytes for both or at least one component to
      beneficially exploit multitopic electrostatic interactions between the deposited
      layers with opposite charges. In contrast, the electrostatic deposition of
      tetracationic 5,10,15,20-tetrakis(1'-methyl-4'-pyridinio)porphyrin tetra(p
      toluenesulfonate) (TMPyP(4+)) with tetraanionic polyoxometalates such as
      EuPW(11)O(39)(4-) or SiW(12)O(40)(4-) onto charged substrates, such as mica, or
      polar substrates, such as glass and indium-tin oxide (ITO), demonstrates that the
      use of polymeric components is not a priori necessary. The use of molecules in
      sequential dipping approaches requires a careful balance in the interaction
      energies between the oppositely charged molecules, as demonstrated by the
      observation that a tetraanionic porphyrin such as 5,10,15,20-tetrakis(4
      sulfonatophenyl)porphyrin does not form layers with TMPyP(4+). In the present
      case, these systems require several rounds of dipping to obtain films of uniform
      coverage and durability. The thin films deposited onto glass, quartz, ITO, and
      mica are surprisingly robust, since they are not removed by sonication in either
      organic solvents or 100 mM NaCl.

PMID- 18321142
TI  - Efficient immobilization and patterning of live bacterial cells.
AB  - A monolayer of live bacterial cells has been patterned onto substrates through
      the interaction between CFA/I fimbriae and the corresponding antibody. Patterns
      of live bacteria have been prepared with cellular resolution on silicon and gold
      substrates for Salmonella enterica serovar Typhimurium as a model with high
      specificity and efficiency. The immobilized cells are capable of dividing in
      growth medium to form a self-sustaining bacterial monolayer on the patterned
      areas. Interestingly, the immobilized cells can alter their orientation on the
      substrate, from lying-down to standing-up, as a response to the cell density
      increase during incubation. This method was successfully used to sort a targeted
      bacterial species from a mixed culture within 2 h.

PMID- 18321143
TI  - Ecological risk assessment in the United States environmental protection agency:
      a historical overview.
AB  - EDITOR'S NOTE: This is 1 of 4 papers from the US Environmental Protection Agency
      Science Advisory Board's Ecological Processes and Effects Committee workshop on
      the current and future practice of ecological risk assessment. The workshop was
      held in Washington, DC in February 2006. Risk assessment originated with the
      insurance industry and spread to the estimation of risks to people and property
      in other contexts, including the regulation of environmental contamination.
      Ecological assessment became an important component of environmental management
      in the United States with the legal mandate for environmental impact assessment
      in 1970. Risk assessment and ecological assessment merged in the 1980s to form
      ecological risk assessment (ERA). Since then, ERA has been institutionalized with
      the development of the US Environmental Protection Agency's (hereafter, USEPA or
      Agency) framework and guidance documents. Ecological risk assessment has been
      adapted by the Agency's program offices to fit their legal and policy contexts.
      The future of ERA will inevitably include the incorporation of more complex and
      demanding methods. However, the biggest challenge for future risk assessors will
      be to make ecological risks more compelling to decision makers.

PMID- 18321145
TI  - Emerging drugs for hepatitis C.
AB  - BACKGROUND: Chronic hepatitis C virus (HCV) infection remains a global health
      threat with approximately 200 million carriers worldwide. Current treatment
      consists of the use of peginterferon (pegIFN)/ribavirin (RBV) for 24 or 48 weeks
      depending on HCV genotype. Serious side effects and the fact that less than half
      of patients infected with HCV genotypes 1 and 4 (which are the most common)
      accomplish sustained virological response with this medication warrant the need
      for novel anti-HCV therapies. OBJECTIVE: Description of specifically targeted
      antiviral therapies for hepatitis C (STAT-C) designed to inhibit the serine
      protease and the RNA-dependent HCV-RNA polymerase. METHODS: Review of available
      data reported in peer-reviewed journals and medical conferences.
      RESULTS/CONCLUSIONS: Early preclinical studies using these compounds produced
      encouraging results, but the initial enthusiasm has been hampered by toxicity
      issues and rapid selection of resistance. Therefore, combination therapy with a
      backbone of pegIFN/RBV, or perhaps in the future using several of these small
      molecules, preferably having distinct modes of action and resistance profiles,
      will be required.

PMID- 18321146
TI  - Emerging vaccines for influenza.
AB  - BACKGROUND: Influenza remains one of the leading causes of morbidity and
      mortality worldwide. The available vaccines are least effective in the
      populations at greatest risk--children, the elderly, and the immunocompromised.
      Furthermore, avian influenza and other novel strains have the potential to cause
      the next influenza pandemic. Research efforts have accelerated worldwide to
      develop new vaccines to provide better immunity against annual epidemics and a
      potential pandemic. OBJECTIVE: To summarize the global research efforts at
      developing new influenza vaccines, adjuvants, and delivery devices. METHOD:
      MEDLINE and Pharmaprojects databases were searched for publications and
      continuing research on new influenza vaccine technologies. RESULTS/CONCLUSIONS:
      Technologies such as DNA vaccines, live recombinant viral vector vaccines, and
      virus-like particles have shown significant promise for immunogenicity and
      protection from experimental challenge to influenza. New modalities for vaccine
      delivery and methods for rapid vaccine production are also being investigated.
      With the possibility of an influenza pandemic increasing the need to develop new
      vaccines, the global research community has made large strides to meet this
      challenge.

PMID- 18321147
TI  - The potential impact of a prophylactic herpes simplex vaccine.
AB  - BACKGROUND: Herpes simplex virus (HSV) infections have a significant impact on
      health causing a wide range of diseases. Oral-facial and genital sites are the
      most common locations of infection and may lead to recurrent painful lesions. HSV
      infection acquired perinatally may result in severe sequelae or even death
      despite appropriate therapy. Furthermore, it is becoming increasingly clear that
      genital HSV infections significantly raise the risk of HIV transmission.
      OBJECTIVE: To describe the strategies, impediments, and advancements in the
      development of vaccines to prevent HSV disease. METHODS: A review of the
      literature was performed, limited to prophylactic HSV vaccines and their
      potential effect on genital herpes, oral-facial disease, and perinatal herpes.
      CONCLUSION: There are several vaccine strategies under development that show
      promise for the treatment these diseases.

PMID- 18321148
TI  - Emerging therapies for fibromyalgia.
AB  - BACKGROUND: Fibromyalgia syndrome (FMS) is a disorder characterized by widespread
      pain, tenderness, and fatigue. High prevalence marks the syndrome which is
      considered to reflect altered central pain processing. Fibromyalgia syndrome runs
      a chronic, non-progressive course, extracting high price owing to impaired
      quality of life, restricted vocational capacity, and increased health care
      utilization. OBJECTIVE: To review current and emerging trends in the treatment of
      FMS. METHODS: A rigorous search of published literature, abstract presentations,
      and industry provided data was performed. RESULTS/CONCLUSION: The recent FDA
      approval of pregabalin as a first specific medication for FMS may herald a new
      era for the development of medications with higher specificity and efficacy for
      this hitherto frustrating condition.

PMID- 18321149
TI  - Emerging drugs for spinal cord injury.
AB  - BACKGROUND: This review summarizes several promising pharmacological approaches
      for the therapeutic management of traumatic spinal cord injury (SCI), which are
      either in early-phase clinical trials or nearing clinical translation. OBJECTIVE:
      This review provides the reader with an understanding of the key
      pathophysiological mechanisms that contribute to neurological deficits after SCI.
      Through discussion of the mechanism(s) of action of the selected therapeutic
      approaches potentially important targets to aid further drug discovery will be
      highlighted. METHODS: Systematic literature review of the pre-clinical literature
      and clinical SCI trials related to neuroprotective, immunomodulatory and
      regenerative therapeutic approaches. RESULTS/CONCLUSION: The next decade will
      witness an unprecedented number of clinical trials which will seek to translate
      key biomedical research discoveries. The promising drug-based therapeutic
      approaches include regenerative strategies to neutralize myelin-mediated neurite
      outgrowth inhibition, neuroprotective strategies to reduce apoptotic triggers,
      the targeting of cationic/glutamatergic toxicity, anti-inflammatory strategies
      and the use of approaches to stabilize disrupted cell membranes.

PMID- 18321150
TI  - Emerging drugs for malignant glioma.
AB  - BACKGROUND: Malignant gliomas are amongst the most devastating and intractable of
      all cancers. The most common malignant glioma, glioblastoma multiforme (GBM), is
      associated with a median survival in the range of 12-15 months. Survival for
      patients with GBM has improved with the addition of temozolomide chemotherapy to
      post-operative radiotherapy. Further advances in the treatment of malignant
      glioma will hinge on the discovery of novel and likely targeted therapies with
      activity against these diseases. OBJECTIVE: Review recent published experience
      using targeted therapeutics for malignant glioma. METHODS: Key studies from a
      Medline review of targeted therapies for malignant glioma performed between 2000
      and the present are summarised in this review. CONCLUSIONS: Experience with
      targeted therapeutics for malignant glioma has been to date disappointing. These
      agents are generally well tolerated, but activity is limited. Novel therapeutics
      with activity against malignant gliomas must be identified to improve prognosis
      for patients with these diseases.

PMID- 18321151
TI  - Emerging drugs for rarer chronic lymphoid leukemias.
AB  - BACKGROUND: Rarer indolent lymphoid leukemias include well defined mature B-cell
      and T-cell neoplasm with widely varying natural history and specific
      morphological, immunophenotypic and molecular characteristics. Among these are
      prolymphocytic leukemia (PLL), hairy cell leukemia (HCL) and its variants, large
      granular lymphocyte leukemia (LGLL) and adult T-cell leukemia/lymphoma (ATLL).
      OBJECTIVE: To present current therapies and emerging drugs potentially useful in
      the treatment of rarer chronic lymphoid leukemias. METHODS: After searching
      MEDLINE, PubMed and the Current Contents database, and conference proceedings
      from the previous 3 years of the American Society of Hematology (ASH), the
      European Society of Hematology (EHA) and the American Society of Clinical
      Oncology (ASCO) were searched manually; articles written in English and
      additional relevant publications were then selected. RESULTS/CONCLUSION: New
      drugs including monoclonal antibodies (mAbs), new purine analogs, small molecules
      targeting specific molecular targets and other agents are included. Future
      research should focus on the novel therapeutic strategies based on the molecular
      pathogenic mechanisms and the development of new targeted therapies for each
      distinct chronic lymphoid leukemia.

PMID- 18321152
TI  - Uterine myoma: a condition amenable to medical therapy?
AB  - BACKGROUND: Uterine myomas are the most common benign tumors of the female
      reproductive tract. Of the different treatment methods available, medical therapy
      may be a less invasive choice. OBJECTIVE: To review the literature on medical
      treatments that are available or being developed for women with uterine myomas.
      METHODS: Literature review of articles pertaining to medical therapeutic
      strategies of uterine myomas. (Articles were searched by means of a computerized
      PubMed and Cochrane Library search with the following keywords: uterine myomas,
      leiomyomata, fibroids, and medical treatment.) RESULTS/CONCLUSION: At present,
      many drugs are available in routine clinical practice, some of which are under
      investigation. This review will explore the recent advances in medical treatment
      for the management of uterine myomas.

PMID- 18321153
TI  - Emerging drugs in the treatment of advanced gastric cancer.
AB  - BACKGROUND: Gastroesopheal cancer is one of the most common cancers worldwide. If
      detected early, curative treatment is possible. Often, gastroesophageal cancer is
      detected at an advanced stage when therapy is palliative. OBJECTIVES: To provide
      a critical evaluation of historic and recently developed chemotherapy regimens
      for the treatment of advanced gastroesophageal cancer (AGC). METHODS: Published
      clinical trials in AGC as well as selected abstracts presented at international
      oncology meetings were selected. RESULTS/CONCLUSION: Chemotherapy has
      demonstrated a benefit over best supportive care alone by improving the quality
      and quantity of life for patients with advanced disease. Recent Phase III trials
      investigating cytotoxic chemotherapy and Phase II trials incorporating biotherapy
      for the treatment of AGC show promise for the future.

PMID- 18321154
TI  - Emerging drugs for non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a condition of emerging
      relevance that includes different forms of chronic liver damage, from a simple
      fatty infiltration (steatosis) of hepatocytes to steatohepatitis (NASH) with
      fibrosis. This last form may evolve to cirrhosis and hepatocellular carcinoma.
      OBJECTIVE: To discuss therapeutic management of NAFLD. Theoretically, only
      patients with non-alcoholic steatohepatitis (NASH) need to be treated, as only
      NASH may evolve to cirrhosis. Differentiation between steatosis and NASH
      currently requires a liver biopsy. METHODS: We discuss different therapeutic
      approaches proposed in literature for patients with NAFLD. RESULTS: The treatment
      of associated conditions leads to an improvement of NAFLD and NASH. No specific
      drug is actually present to treat liver steatosis or NASH. CONCLUSIONS: The
      treatment of NAFLD depends on the individual characteristics of each patient.
      Diet and physical exercise may be considered a basal universal approach. Future
      research will discover possible specific liver drugs.

PMID- 18321155
TI  - Emerging drugs for complications of end-stage liver disease.
AB  - BACKGROUND: The prevalence of end-stage liver disease is rising rapidly and
      constitutes a major healthcare burden currently. Many cases are diagnosed at a
      later stage when liver transplantation is the only effective treatment option.
      There is thus an urgent need for novel treatments to reverse the earlier stages
      of cirrhosis as well as to treat the many associated life-threatening
      complications. OBJECTIVES: To review the current drugs available for treating the
      complications of advanced liver disease. To address novel treatment strategies
      that are in development, with particular reference to the rapidly developing area
      of antifibrotic therapy. To assess how the obstacles that have so far impeded the
      development of effective new drugs for end-stage liver disease may be overcome in
      the future. METHODS: The literature was reviewed to define current therapies and
      therapies in clinical trials. We used the current models of the molecular basis
      of liver fibrogenesis to determine potential new therapeutic targets for
      antifibrotic therapy. CONCLUSIONS: Insights into the pathogenesis of liver injury
      and fibrosis have opened up new avenues for therapy and there are now candidates
      and targets with real potential for the development of a new generation of
      antifibrotic therapies.

PMID- 18321156
TI  - Emerging drugs for rheumatoid arthritis.
AB  - BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic,
      autoimmune disease characterized by symmetric arthritis of diarthrodial joints
      leading to progressive erosion of cartilage and bone. The individual and social
      impacts of RA are of great importance. OBJECTIVE: To investigate the development
      of new therapies for RA treatment. METHODS: Various databases have been searched
      for new drugs in clinical trials (Phase I - III) and experimental future
      therapeutic agents for RA. RESULTS/CONCLUSION: The current management of the
      disease includes the use of disease modifying anti-rheumatic drugs and the
      biologic therapies. Progress in our understanding of RA pathophysiology led to
      the identification of new therapeutic targets. These include pro-inflammatory
      cytokines, T and B cells, adhesion molecules, chemokines and intra- and
      extracellular signaling pathways. Therapeutic modulation of the above targets can
      provide new treatment strategies. This article reviews a few of the new treatment
      strategies currently being evaluated.

PMID- 18321157
TI  - Treatment perspectives for the lysosomal storage diseases.
AB  - BACKGROUND: The therapy of the lysosomal storage diseases (LSDs) was developed by
      supplying adequate amounts of the needed enzyme to affected individuals. This
      approach in Gaucher disease provided a prototype for the basic and clinical
      sciences, and the economic foundation for other ultra-orphan diseases. OBJECTIVE:
      Using the success of enzyme therapy for Gaucher disease, the challenges are
      highlighted for alternative bioproduction systems, and substrate reduction and
      molecular chaperone approaches for treatment of Gaucher disease and other ultra
      orphan diseases. METHODS: Literature review provided insight into the current
      status of enzyme therapies for LSDs, the proposed mechanisms of alternative
      approaches to therapy, and the obstacles in a competitive marketplace for
      treatment of ultra-rare diseases. RESULTS/CONCLUSIONS: These developments are
      placed in the contexts of finding rare patients with LSDs, their marked
      phenotypic spectrum, potential markets, and new orphan drug costs. The confluence
      of these challenges has led to a competitive environment with the potential for
      multiple, alternative, expensive treatments for orphan diseases.

PMID- 18321158
TI  - Molecular design guided by a local map of sequence space: DNA aptamers that
      inhibit cathepsin E.
AB  - It has been strongly demanded by a number of people to elevate activities of
      molecules of a particular function. Currently, there is no general guide
      available for this purpose. Here we present a novel approach for this; a local
      sequence space map-directed method for exploring molecules of a higher activity.
      This approach exploits the knowledge of a local sequence space so far established
      and obtains the shape of sequence space (map) by intra- and extrapolating the
      known landscape, which was drawn through the principal coordinates analysis. In
      this method, we successfully obtained 16 DNA aptamers of cathepsin E (CE)
      inhibitory activity that have comparable or higher activities than the ancestral
      ones on which the designed molecules were based. Some of them had a 30% higher
      activity than the previously reported top one (SFR-6-3). This high efficiency in
      obtaining functional molecules (16 out of 21 newly designed ones) is by no means
      usual because most of molecules generated at random are known to have no
      function, showing the effectiveness of the map-based approach. The selected
      molecules were confirmed to have the i-motif structure, consistent to the fact
      that they have a C-rich sequence and their CE-inhibitory activities were measured
      at an acidic pH, both of which are favorable for the i-motif. This structure of
      CE-inhibitory aptamers was inferred to contribute to the structural stability but
      not to the function itself directly.

PMID- 18321159
TI  - Single acute-dose and repeat-doses toxicity of anti-HIV-1 PNA TAR-penetratin
      conjugate after intraperitoneal administration to mice.
AB  - Polyamide (peptide) nucleic acids conjugated with membrane-penetrating peptide
      are potential antisense therapeutic agents because of their unique chemical
      properties, high target specificity, and efficient cellular uptake. However,
      studies of their potential toxicity in animal models are lacking. In this study,
      we evaluated the toxicity of the response of Balb/C mice to anti-HIV-1 PNA TAR
      penetratin conjugate targeted against the transactivation response (TAR) element
      of HIV-1 LTR. A single i.p. dose of 600 mg/kg of body weight was lethal, killing
      all mice within 72 hours. However, death did not occur after single doses of 100
      and 300 mg/kg, although all mice experienced initial and transitory diarrhea and
      loss of agility. Repeated daily doses of 10, 30, and 100 mg/kg were well
      tolerated by mice during 8 days of treatment, although daily doses of 100 mg/kg
      caused diarrhea during the first 4 days of treatment. During 8 weeks of follow
      up, mice fully recuperated. Serositis was observed in the spleens, livers, and
      kidneys at the ninth day of treatment, but not after the follow-up period.
      Necropsies, clinical chemistry studies, and hematological parameters demonstrated
      normal function of the major organs and no irreversible damage to the mice. These
      observations indicate that the PNA-peptide conjugate would be nontoxic at
      probable therapeutic doses and thus support its therapeutic potential as an
      antisense drug.

PMID- 18321160
TI  - Double-stranded break can be repaired by single-stranded oligonucleotides via the
      ATM/ATR pathway in mammalian cells.
AB  - Single-stranded oligonucleotide (SSO)-mediated gene modification is a newly
      developed tool for site-specific gene repair in mammalian cells; however, the
      corrected cells always show G2/M arrest and cannot divide to form colonies. This
      phenomenon and the unclear mechanism seriously challenge the future application
      of this technique. In this study, we developed an efficient SSO-mediated DNA
      repair system based on double-stranded break (DSB) induction. We generated a
      mutant EGFP gene with insertions of 24 bp to 1.6 kb in length as a reporter
      integrated in mammalian cell lines. SSOs were successfully used to delete the
      insertion fragments upon DSB induction at a site near the insertion. We
      demonstrated that this process is dependent on the ATM/ATR pathway. Importantly,
      repaired cell clones were viable. Effects of deletion length, SSO length, strand
      bias, and SSO modification on gene repair frequency were also investigated.

PMID- 18321161
TI  - Biodistribution of 68Ga-labeled LNA-DNA mixmer antisense oligonucleotides for rat
      chromogranin-A.
AB  - In vivo monitoring of gene expression may be accomplished using a most advanced
      imaging technology such as positron emission tomography (PET). However, a range
      of methodological and biological hurdles needs exploration. In the present study,
      20-mer DNA-LNA (locked nucleic acid) mixmer oligonucleotides specific for rat
      Chromogranin-A (Chg-A) mRNA were labeled with 68Ga and their biodistribution were
      investigated in rats; namely, two Antisense (LNA1, LNA2--differing only in the
      positioning of LNA modification), Mismatched, and Sense sequences. In addition,
      in vivo and in vitro metabolite analysis of LNA1 and LNA2 was compared, and
      hybridization in solution was performed to verify the hybridization ability after
      labeling. Furthermore, semiquantitative polymerase chain reaction was carried out
      to find organs expressing Chg-A mRNA in the rat. The biodistribution patterns
      altered according to the sequence and the positioning of LNA modification. The
      pattern of Mismatched--differing only in two nucleotides from the two Antisenses-
      was similar to that of Sense, whereas the pattern of LNA1 and LNA2 showed
      differences. Uptake in the adrenal gland was twofold higher with LNA2 compared to
      the other three oligonucleotides. Intact LNA2 could be observed in the 60-minute
      sample in vivo, whereas in vitro, the intact compound of both Antisenses could
      also be detected after 2 hours. Hybridization in solution revealed that the two
      Antisenses retained their hybridization abilities after 68Ga-labeling. With
      decreasing magnitude, Chg-A mRNA was expressed in the adrenal gland, intestine,
      testis, and pancreas. This study further supported LNA-DNA mixmer to be a
      favorable modification for antisense targeting approach with respect to
      hybridization and longer plasma residence; however, the organ uptake was
      dominated by processes irrelevant to specific hybridization.

PMID- 18321162
TI  - G-rich oligonucleotides alter cell cycle progression and induce apoptosis
      specifically in OE19 esophageal tumor cells.
AB  - Short synthetic oligonucleotides (ODNs) can be used to block cellular processes
      involved in cell growth and proliferation. Often acting as aptamers, these
      molecules interact with critical proteins that regulate the induction of
      apoptosis or necrosis. We have used a specialized class of ODNs that contain a
      monomeric sequence of guanosine to induce apoptosis specifically in the malignant
      esophageal cell line, OE19, in cell culture, and in a NODscid mouse model. OE19
      cells were grown in culture and treated with a stable G-rich oligonucleotide
      (GRO). Cells were processed and apoptosis was measured by FACS analyses, caspase
      activity, and Hoescht staining. Circular dichroism (CD) was used to define the
      structure and stability of various GROs. The GRO works by first inducing
      retardation in the progression of the cell cycle and then by creating a sub-G1
      population of apoptotic cells. The reaction is dose dependent, and appears to
      rely on the capacity of the G-rich ODN to adopt a G-quartet conformation.
      Apoptosis was measured by determining caspase 3/7 levels and by staining for
      nuclear fragmentation using the Hoechst dye. Importantly, nonmalignant esophageal
      cells or normal human lung fibroblasts are not impeded in their cell cycle
      progression when incubated with the G-rich ODNs. These results suggest that a
      selective killing of esophageal tumor cells is directed by G-rich ODNs. Selective
      killing was demonstrated in the unique activity of the GRO compared to other ODNs
      of different sequences as well as the response of oncogenic cells compared to
      nononcogenic cells.

PMID- 18321163
TI  - DNase I-tRNA interaction.
AB  - Deoxyribonuclease I (DNase I) binds right-handed DNA duplex via a minor groove
      and the backbone phosphate group with no contact to the major groove. It
      hydrolyses double-stranded DNA predominantly by a single-stranded nicking
      mechanism under physiological conditions, in the presence of divalent Mg and Ca
      cations. Even though DNase-RNA interaction was observed, less is known about the
      protein-RNA binding mode and the effect of such complexation on both protein and
      RNA conformations. The aim of this study was to examine the effects of DNase I
      tRNA interaction on tRNA and protein conformations. The interaction of DNase I
      with tRNA is monitored under physiological conditions, in the absence of Mg2+,
      using constant DNA concentration of 12.5 mM (phosphate) and various protein
      contents (10 microM to 250 microM). FTIR, UV-visible, and CD spectroscopic
      methods were used to analyze the protein binding mode, the binding constant, and
      the effects of polynucleotide-enzyme interaction on both tRNA and protein
      conformations. Spectroscopic evidence showed major DNase-PO2 and minor groove
      interactions with overall binding constant of K = 2.1 (+/-0.7) x 10(4) M(-1). The
      DNase I-tRNA interaction alters protein secondary structure with major reduction
      of the alpha-helix, and increases the random coil, beta-anti and turn structures,
      while tRNA remains in the A-conformation. No digestion of tRNA by DNase I was
      observed in the protein-tRNA complexes.

PMID- 18321164
TI  - Investigation of the interaction between ssDNA and 2-aminophenoxazine-3-one and
      development of an electrochemical DNA biosensor.
AB  - An electrochemical method was used to probe the interaction between 2
      aminophenoxazine-3-one (AP) and the short DNA sequence related to the hepatitis B
      virus (HBV), and an electrochemical DNA biosensor was developed. The voltammetric
      signals of AP have been investigated at bare glassy carbon electrode (bare GCE),
      hybrid double-stranded DNA-modified GCE (dsDNA/GCE), and single-stranded DNA
      modified GCE (ssDNA/GCE) by means of differential pulse voltammetry (DPV), and
      the peak currents increased with respect to the order of electrodes. The extent
      of hybridization was evaluated on the basis of the difference between signals of
      AP with a probe before and after hybridization with the complementary sequence.
      Control experiments with noncomplementary were performed to test the selectivity
      of the biosensor. With this approach, a sequence of the HBV could be quantified
      over the range from 3.53 x 10(-7) to 1.08 x 10(-6) M, with a linear correlation
      of r = 0.9963 and a detection limit of 1.00 x 10(-7) M.

PMID- 18321165
TI  - Fast deprotection of synthetic oligodeoxyribonucleotides using standard reagents
      under microwave irradiation.
AB  - Fast methods for the removal of permanent amide exo-cyclic protective groups
      widely used in phosphoramidite-method DNA synthesis are desirable for many
      genomics and proteomics applications. In this communication, we present a method
      for the deprotection of a range of N-acyl deoxyribonucleosides (T, dA Bz, dC Bz,
      dC Ac, dG ibu, dG PAC) and synthetic oligodeoxyribonucleotides, ranging in length
      from 5-mer to 50-mer. Oligodeoxyribonucleotides were synthesized using standard
      amide protecting groups (dA Bz, dC Bz, dG ibu) and phosphoramidite chemistry on
      cis-diol solid phase support. This deprotection method utilizes 29% aqueous
      ammonia solution at 170 degrees C for 5 minutes under monomode microwave
      irradiation at a 20-nmole reaction scale. Reaction products were analyzed by TLC,
      RP-HPLC, CE, ESI-MS, real-time PCR, agarose gel electrophoresis, and by DNA
      uracil glycosylase (UDG) and phosphodiesterase I (PDE) enzymatic digestions.

PMID- 18321166
TI  - Sequestering of the 3' splice site in a theophylline-responsive riboswitch allows
      ligand-dependent control of alternative splicing.
AB  - Despite the important role of alternative splicing in various aspects of
      biological processes, our ability to regulate this process at will remains a
      challenge. In this report, we asked whether a theophylline-responsive riboswitch
      could be adapted to manipulate alternative splicing. We constructed a pre-mRNA
      containing a single upstream 5' splice site and two 3' splice sites, of which the
      proximal 3' splice site is embedded in theophylline-responsive riboswitch. We
      show that this pre-mRNA spliced with preferential utilization of proximal 3'
      splice site in vitro. However, addition of theophylline to the splicing reaction
      promoted splicing at distal 3' splice site thereby changing the ratio of distal
      to-proximal 3' splice site usage by more than twofold. Our data suggest that
      theophylline influenced 3' splice site choice without affecting the kinetics of
      the splicing reaction. We conclude that an in vitro selected riboswitch can be
      adapted to control alternative splicing, which may find many applications in
      basic, biotechnological, and biomedical research.

PMID- 18321168
TI  - Focusing on public health: a different look at translating research to practice.
AB  - ABSTRACT The Centers for Disease Control and Prevention (CDC) is committed to
      achieving true improvements in people's health. In chronic disease prevention and
      health promotion, we have a good deal of evidence about which intervention
      strategies work in clinics and in communities to improve health, but we need to
      accelerate translating that evidence into practice. This paper provides an
      overview of initial efforts of the National Center for Chronic Disease Prevention
      and Health Promotion (NCCDPHP) within the CDC to identify and organize the
      fundamental elements of translation, with the goal of understanding what our
      constituents need for success and to identify key issues to consider in
      translation.

PMID- 18321169
TI  - Toward optimal health: reframing medical care to reflect a global perspective.

PMID- 18321170
TI  - Lipid-lowering medication use and aggression scores in women: a report from the
      NHLBI-sponsored WISE study.
AB  - AIM: The aim of this study was to examine the association between the use of
      lipid-lowering medication and aggressive responding, hostility, cynicism, and
      depression scores in women undergoing coronary angiography. METHODS: The cohort
      included 498 women from the National Heart, Lung and Blood Institute (NHLBI)
      sponsored Women's Ischemia Syndrome Evaluation (WISE) study. WISE is a four
      center study of women with chest pain who underwent quantitative coronary
      angiography for suspected myocardial ischemia. The psychosocial indices included
      the Cook Medley Hostility questionnaire, measuring aggression, hostility, and
      cynicism, and the Beck Depression Inventory (BDI). RESULTS: Compared to those not
      on lipid-lowering medication, women receiving lipid-lowering pharmacotherapy were
      older (62 vs. 55 years, p < 0.001) and had more hypertension, dyslipidemia,
      diabetes, and coronary artery disease (CAD, defined as > or =50% stenoses in at
      least one epicardial artery) (all p < 0.003). Women on lipid-lowering medication
      had higher aggressive responding scores than those not on medication, 3.0 +/- 1.8
      vs. 2.7 +/- 1.7, respectively (age-adjusted p < 0.003). This association
      persisted after adjustment for coronary risk factors, education, and extent of
      angiographic disease (CAD) (p < 0.005), and after exclusion of women using
      psychotropic medications (p < 0.001). Hostility, cynicism, and depression scores
      did not differ by medication use.

PMID- 18321171
TI  - Does gender discrimination impact regular mammography screening? Findings from
      the race differences in screening mammography study.
AB  - ABSTRACT Objective: To determine if gender discrimination, conceptualized as a
      negative life stressor, is a deterrent to adherence to mammography screening
      guidelines. METHODS: African American and white women (1451) aged 40-79 years who
      obtained an index screening mammogram at one of five urban hospitals in
      Connecticut between October 1996 and January 1998 were enrolled in this study.
      This logistic regression analysis includes the 1229 women who completed telephone
      interviews at baseline and follow-up (average 29.4 months later) and for whom the
      study outcome, nonadherence to age-specific mammography screening guidelines, was
      determined. Gender discrimination was measured as lifetime experience in seven
      possible situations. RESULTS: Gender discrimination, reported by nearly 38% of
      the study population, was significantly associated with nonadherence to
      mammography guidelines in women with annual family incomes of > or =$50,000 (OR
      1.99, 95% CI 1.33, 2.98) and did not differ across racial/ethnic group.
      CONCLUSIONS: Our findings suggest that gender discrimination can adversely
      influence regular mammography screening in some women. With nearly half of women
      nonadherent to screening mammography guidelines in this study and with decreasing
      mammography rates nationwide, it is important to address the complexity of
      nonadherence across subgroups of women. Life stressors, such as experiences of
      gender discrimination, may have considerable consequences, potentially
      influencing health prevention prioritization in women.

PMID- 18321172
TI  - Gender differences in research grant applications and funding outcomes for
      medical school faculty.
AB  - PURPOSE: To evaluate whether there were differences in acquisition of research
      grant support between male and female faculty at eight Harvard Medical School
      affiliated institutions. METHODS: Data were obtained from the participating
      institutions on all research grant applications submitted by full-time faculty
      from 2001 through 2003. Data were analyzed by gender and faculty rank of
      applicant, source of support (federal or nonfederal), funding outcome, amount of
      funding requested, and amount of funding awarded. RESULTS: Data on 6319 grant
      applications submitted by 2480 faculty applicants were analyzed. Women
      represented 29% of investigators and submitted 26% of all grant requests. There
      were significant gender differences in the mean number of submissions per
      applicant (women 2.3, men 2.7), success rate (women 41%, men 45%), number of
      years requested (women 3.1, men 3.4), median annual amount requested (women
      $115,325, men $150,000), mean number of years awarded (women 2.9, men 3.2), and
      median annual amount awarded (women $98,094, men $125,000). After controlling for
      academic rank, grant success rates were not significantly different between women
      and men, although submission rates by women were significantly lower at the
      lowest faculty rank. Although there was no difference in the proportion of money
      awarded to money requested, women were awarded significantly less money than men
      at the ranks of instructor and associate professor. More men than women applied
      to the National Institutes of Health, which awarded higher dollar amounts than
      other funding sources. CONCLUSIONS: Gender disparity in grant funding is largely
      explained by gender disparities in academic rank. Controlling for rank, women and
      men were equally successful in acquiring grants. However, gender differences in
      grant application behavior at lower academic ranks also contribute to gender
      disparity in grant funding for medical science.

PMID- 18321173
TI  - Healthcare preferences among lesbians: a focus group analysis.
AB  - OBJECTIVE: The healthcare needs of lesbians are not well understood. We sought to
      characterize lesbians' experiences with, and preferences for, women's healthcare.
      METHODS: We conducted three age-stratified focus groups (18-29, 30-50, and >50
      years) with a total of 22 participants using a semistructured interview guide to
      elicit lesbians' experiences and preferences. We analyzed transcripts of these
      audiotaped sessions using the constant comparative method of grounded theory.
      Community-dwelling women who self-identified as lesbian and responded to
      advertisements were selected on first-come basis. RESULTS: Participants voiced
      experiences and preferences for healthcare that emerged into three themes:
      desired models of care, desired processes of care, and desired patient-provider
      relationship. Each theme was further developed into multiple subthemes. Within
      the subthemes we identified issues that were specific to lesbians and those that
      were general women's health issues. Participants preferred, but did not always
      receive, care that is comprehensive in scope, person centered, nondiscriminatory,
      and inclusive of them as lesbians. CONCLUSIONS: Healthcare providers,
      institutions, and society should adopt an inviting, person-centered approach
      toward lesbians seeking healthcare, assure them access to healthcare information,
      and establish healthcare delivery systems that take all aspects of health into
      account.

PMID- 18321174
TI  - The reciprocal effects of eating disorders and the postpartum period: a review of
      the literature and recommendations for clinical care.
AB  - This paper examines the areas of psychological and physiological concern when
      working with patients who have eating disorders as they move through the
      postpartum period. These concerns include infant feeding, maternal-child bonding,
      and postpartum adjustment. The combination of psychological stressors of new
      motherhood and body image concerns intensified by the residual bodily changes of
      pregnancy may predispose women to have an exacerbation in eating disordered
      symptoms as well as the development of postpartum mood disorders. Depression can
      lead mothers to be nonresponsive, inconsistent, or rejecting of the infant,
      placing the mother-baby attachment at risk. The added existence of an eating
      disorder compounds these risks, with medical and psychological risks becoming
      increasingly apparent. Healthcare providers (e.g., primary care physician,
      obstetric provider) are more likely to have contact with women during the
      postpartum period, making such providers instrumental in the screening and
      referral process. A multidisciplinary approach is recommended for treating eating
      disorders and related conditions. Unfortunately, there is little information
      about the efficacy and appropriateness of standard eating disorder treatments for
      women in the postpartum period. In addition to reviewing the literature, guidance
      is offered on how to assess and treat patients with eating disorders in general
      as well as considerations specific to the postpartum period.

PMID- 18321175
TI  - A prospective, controlled multisite study of psychosocial and behavioral change
      following women's cardiac rehabilitation participation.
AB  - BACKGROUND: Despite its proven benefits and need, women are significantly less
      likely than men to participate in and complete cardiac rehabilitation (CR). Thus,
      there are few reports of CR outcomes among women, particularly when compared with
      women who do not participate in CR. The purpose of this study was to
      prospectively assess psychosocial and behavioral changes, comparing women who
      participated in CR with those who did not. METHODS: One hundred fifty-seven
      female cardiac inpatients from three hospitals consented to participate in a
      prospective study, and 110 (79%) were retained 18 months postdischarge. A mailed
      survey discerned CR participation 9 months postdischarge. Quality of life (Short
      Form Health Survey Physical and Mental Component Summary [SF-12 PCS and MCS]),
      exercise behavior (Health-Promoting Lifestyle Profile II [HPLPII]), Exercise
      Benefits and Barriers Scale (EBBS), and anxiety and depressive symptoms (Hospital
      Anxiety and Depression Scale [HADS]) were assessed in hospital and 18 months
      postdischarge. RESULTS: Fifty-one (45.1%) women self-reported participating in CR
      at 1 of 18 sites, and site-verified participation was 82.43% +/- 29.97% of
      prescribed sessions. For CR participants, paired t tests assessing change from
      hospitalization to 18 months postdischarge revealed significant improvements in
      physical quality of life (p < 0.001), anxiety (p < 0.05), and exercise behavior
      (p = 0.01). Women who did not participate in CR experienced significant
      improvements in physical quality of life (p = 0.02), and depressive symptoms (p =
      0.03) but not exercise behavior. CONCLUSIONS: Following a cardiac event, female
      patients improved their physical quality of life and affect, but only patients
      who participated in CR increased their exercise behavior. Given the cardiac
      benefits of exercise and that women are often sedentary and given that this
      exercise behavior was sustained post-CR, these findings are significant.
      Randomized controlled trials of women's CR outcomes are needed.

PMID- 18321176
TI  - Type 2 diabetes among women: clinical considerations for pharmacological
      management to achieve glycemic control and reduce cardiovascular risk.
AB  - The purpose of this paper is to highlight specific considerations in the medical
      management of women with type 2 diabetes mellitus (T2DM). T2DM, a significant
      source of morbidity and mortality, has become an ever growing epidemic within the
      United States. Although it is well understood that diabetes can significantly
      increase the risk for microvascular and macrovascular complications, there has
      been limited research examining the differential impact of these complications on
      men and women. Women, in particular, are subject to especially high risk for the
      development of myocardial infarction (MI), claudication, and stroke and are
      disproportionately afflicted by cardiovascular, cerebrovascular, and peripheral
      vascular disease. There is new evidence that tight glycemic control and earlier
      initiation of insulin therapy can improve outcomes and thereby reduce the risk
      for development of both macrovascular and microvascular complications of the
      disease. Although there are many commonalities in the treatment of men and women,
      women with diabetes have several unique issues, including the possible effects of
      therapy on reproductive health, fetal health, breastfeeding, potential
      interactions with hormonal contraceptives, and effects on bone health, that
      should be considered when determining a therapeutic approach. This paper presents
      evidence-based treatment strategies for reducing the risk of diabetes-associated
      complications overall and cardiovascular disease in particular through glycemic
      control. Special attention is paid to the selection of antidiabetic agents that
      are best suited to the unique needs of women.

PMID- 18321177
TI  - Ha sentido sola? Culturally competent screening for intimate partner violence in
      Latina women.
AB  - OBJECTIVE: Intimate partner violence (IPV), a common public health problem,
      affects women irrespective of ethnicity. Primary care visits provide an excellent
      opportunity to identify IPV survivors; however, among immigrant Latina women,
      language can be a barrier. Several IPV screening instruments are available in
      English, but few are available in Spanish. Therefore, we sought to estimate the
      screening characteristics of seven validated screening questions translated into
      Spanish. METHODS: Participants included 105 Spanish-speaking Latina women, aged
      18-64 years, seen for primary care in an urban teaching hospital. Measures used
      were (1) screening questions: seven dichotomous response-option IPV screening
      questions, and (2) comparison standard: Index of Spouse Abuse (ISA), adapted for
      lifetime IPV. All measures were professionally translated into Spanish.
      Sensitivity and specificity, with 95% confidence intervals (CI), of all questions
      were estimated using 2 x 2 tables. Sensitivity and specificity with 95% CIs were
      estimated for the two questions with highest sensitivity. RESULTS: Mean age was
      38.5 years (SD 11.4); 89.5% were uninsured, and 33% reported lifetime IPV.
      Spanish translations of the following questions: "Have you ever been in a
      relationship where you have felt controlled by your partner?" and "Have you ever
      been in a relationship where you have felt lonely?" had the highest individual
      sensitivity. The sensitivity of an affirmative response to either question was
      94% (95% CI 86%, 100%), and the specificity of an affirmative response to both
      questions was 86% (95% CI 78%, 94%). CONCLUSIONS: Simple screening questions used
      in combination are highly sensitive for IPV detection in immigrant Latina women
      and may assist clinicians caring for them to identify a history of IPV.

PMID- 18321178
TI  - Accessing care: use of a specialized women's emergency care facility for
      nonemergent problems.
AB  - OBJECTIVE: Given the problem of emergency room overcrowding, this study was
      designed to examine factors associated with women seeking treatment for medically
      nonemergent conditions in a primarily obstetric and gynecologic emergency
      facility. METHODS: This is a prospective study of 287 women coming for non
      emergent reasons to the Women & Infants Hospital Emergency Room/Triage Unit (WIH
      ER/Triage Unit). Participants completed questionnaires to assess reasons for
      choosing to seek care in the emergency room, symptoms, and past medical care.
      Data abstracted and analyzed from the participants' medical records included
      demographic information, recorded urgency level, pregnancy status, and medical
      reasons for the visit. RESULTS: Of the 287 women completing the questionnaire,
      36% came because they believed they had a true emergency, 42% because of
      physician referral, and 21% because of access barriers. Eighty-four percent of
      participants reported having a primary physician, and 56% registered for care on
      weekdays between 9 AM and 5 PM. Seventy percent reported a reason for the visit
      that was related to either obstetrics or gynecology. Common symptoms among women
      coming to this emergency department (ED) included abdominal or pelvic pain (32%)
      and vaginal bleeding (22%). Seventeen percent came for diagnostic testing, such
      as ultrasound or laboratory testing. CONCLUSIONS: Although women with nonemergent
      medical conditions who came to a specialized emergency facility for care had a
      usual source of medical care, that source of care was not always accessible or
      available to them.

PMID- 18321179
TI  - The prevalence of cervical HPV and cytological abnormalities in association with
      reproductive factors of rural Nigerian women.
AB  - OBJECTIVE: To estimate the prevalence of cervical human papillomavirus (HPV) and
      cytological abnormalities while addressing demographic and reproductive variables
      in a sample of rural Nigerian patients. METHODS: In March 2004, a medical project
      was conducted in Okene, Nigeria. The obstetrics/gynecology team collected
      demographics of 231 patients and 199 ThinPrep Pap smears (Cytyc, Marlborough,
      MA), which were analyzed cytologically and for the presence of HPV DNA. RESULTS:
      Of 231 patients (mean age 32.2), 76% had seen a physician four times or less.
      From 199 Pap smears performed, 21.6% had high-risk (HR) HPV, low-risk (LR) HPV,
      or both. HR HPV was present in 16.6% of the women. There were 13 (6.5%) abnormal
      Pap smears, of which 9 (4.5%) had atypical squamous cells of undetermined
      significance (ASCUS), 1 (0.5%) had atypical glandular cells (AGC), 2 (1%) had low
      grade squamous intraepithelial lesions (LSIL), and 1 (0.5%) had a high-grade SIL
      (HSIL). Other findings were Trichomonas vaginalis in 18 patients (9%) and Candida
      in 27 patients (13.5%). CONCLUSIONS: The prevalence of cervical HPV and SIL in
      Okene, Nigeria, is consistent with reports from other African regions. Improved
      access to healthcare and cervical cancer screening programs may help to decrease
      transmission of HPV and subsequent cervical cancer in underprivileged areas.

PMID- 18321180
TI  - Menstrual cycle phase at quit date predicts smoking status in an NRT treatment
      trial: a retrospective analysis.
AB  - BACKGROUND AND OBJECTIVE: The deleterious health consequences of smoking are even
      more severe for women, yet ironically, they have more difficulty quitting than
      men. Identifying relapse predictors for women and implementing strategies to
      increase their chances of successfully quitting and remaining abstinent are
      important goals. Clinicians and researchers suggest that women could achieve
      greater success in smoking cessation interventions if the initial quit attempt
      coincided with the follicular phase (i.e., preovulatory phase) of their menstrual
      cycle (MC) rather than the luteal phase (i.e., premenstrual). However, no
      experimental data have been published to support this claim. Our objective was to
      determine whether MC phase affected smoking status in premenopausal female
      smokers participating in a smoking cessation treatment trial. METHODS: Data from
      102 treatment-seeking smokers who participated in an 8-week nicotine replacement
      therapy (NRT) plus behavioral intervention smoking cessation study were examined
      retrospectively. NRT began the day subjects attempted to quit smoking (quit
      date). For analyses, smokers were grouped according to sex, and women were
      subdivided by MC phase at quit date into follicular (FF, days 1-14, n = 16) and
      luteal (LF, days 15-30, n = 21) groups. RESULTS: Smoking status was examined on
      the third day after the quit date (day 3) and at 1 week posttreatment (week 9).
      On day 3, 52% of LFs reported smoking compared with 19% of FFs (p < 0.04), and at
      week 9, 71% of LFs reported smoking compared with 31% of FFs (p < 0.02). In a
      comparison group of men (n = 65), 25% were smoking at day 3 and 68% at week 9.
      Self-report at week 9 was verified by urine cotinine levels. CONCLUSIONS: These
      data support the supposition that better treatment outcomes can be achieved by
      scheduling quit dates to coincide with the follicular phase of the MC in female
      smokers.

PMID- 18321181
TI  - Menstrual phase effects on smoking cessation: a pilot feasibility study.
AB  - BACKGROUND AND OBJECTIVES: A growing body of research suggests that nicotine
      withdrawal and cigarette craving may vary across the menstrual cycle and that the
      luteal phase of the cycle may be associated with increases in each. This
      potential relationship suggests that careful timing of quit attempts during the
      menstrual cycle may improve initial success at abstinence, although there are no
      direct tests of this approach yet published. Our objectives were to preliminarily
      test the effect of timing of quit attempts for smoking cessation relative to
      menstrual cycle and to identify methodological procedures that could guide
      subsequent, larger clinical trials. METHODS: In this pilot study, we randomized
      female smokers aged 18-40 who were not currently using hormonal contraception to
      quit smoking during either the follicular (n = 25) or luteal phase (n = 19) of
      their menstrual cycle. Participants were provided with two sessions of smoking
      cessation counseling (90 minutes total). All participants were provided with a
      transdermal nicotine patch contingent on maintenance of abstinence throughout the
      course of the 6-week study. RESULTS: Among participants who initiated treatment,
      received the patch, and made a quit attempt (n = 35), carbon monoxide-verified
      repeated point prevalence abstinence 2 weeks after the target quit date was
      higher in the follicular than the luteal group (32% vs. 19%, respectively; OR =
      2.0, 95% CI = 0.4-9.8). Within the overall study population, this difference was
      slightly lower (24% vs. 16%; OR = 1.7, 95% CI = 0.4-7.8). CONCLUSIONS: Timing
      quit attempts based on menstrual phase is feasible. Insights gained from this
      study and the recommendations made herein may inform future research on this
      important clinical question.

PMID- 18321182
TI  - Comment on "gender differences in research grant applications and funding
      outcomes for medical school faculty".

PMID- 18321183
TI  - Polyubiquitin promoter-based binary vectors for overexpression and gene silencing
      in Lotus japonicus.
AB  - In this study, we compared the transcriptional activities between Cauliflower
      mosaic virus (CaMV)35S promoter and polyubiquitin (Ljubq1) promoter from Lotus
      japonicus using beta-glucuronidase (gus) reporter gene in transgenic plants of L.
      japonicus. The promoter analysis demonstrated that the Ljubq1 promoter possessed
      higher activity than the CaMV35S promoter in leaves, stems, roots, nodules, and
      pollen. Finally, we created GATEWAY conversion technology-compatible binary
      vectors for over-expression and RNA interference under the Ljubq1 promoter. These
      materials could provide alternative choice for studies in L. japonicus.

PMID- 18321184
TI  - Pathogenicity of Pseudomonas syringae pv. tomato on tomato seedlings: phenotypic
      and gene expression analyses of the virulence function of coronatine.
AB  - Bacterial speck disease, which is caused by Pseudomonas syringae pv. tomato, is
      an economically important disease on tomato. In the present study, we show that
      P. syringae pv. tomato DC3000 is a pathogen of tomato seedlings, an aspect of
      pathogen biology that has not been previously investigated. This resulted in the
      development of a virulence assay on tomato seedlings that has several advantages
      over labor-intensive foliar assays, including a shorter growth and incubation
      period, ease of inoculation and handling, and rapid generation of larger sample
      sizes per experiment. The utility of this assay was investigated by exploring the
      virulence function of coronatine (COR) on tomato seedlings. Using the COR- mutant
      DB29 and a MAPMAN display of transcript data from TOM1 microarrays, COR-dependent
      expression of genes involved in secondary metabolism, polyamine biosynthesis,
      reactive oxygen species homeostasis, and the novel transcription factor SlNAC2
      were identified. Furthermore, during pathogenesis, genes involved in
      photosynthetic light reactions and the Calvin-Benson cycle were strongly
      repressed by COR. In conclusion, we show that P. syringae pv. tomato infects
      tomato seedlings and that COR is required for virulence in seedlings. The
      seedling assay can be used in high-throughput screens for the identification of
      molecular targets for COR and for the identification of genes involved in
      pathogenesis.

PMID- 18321185
TI  - Identification of a new locus, Ptr(t), required for rice blast resistance gene Pi
      ta-mediated resistance.
AB  - Resistance to the blast pathogen Magnaporthe oryzae is proposed to be initiated
      by physical binding of a putative cytoplasmic receptor encoded by a nucleotide
      binding site-type resistance gene, Pi-ta, to the processed elicitor encoded by
      the corresponding avirulence gene AVR-Pita. Here, we report the identification of
      a new locus, Ptr(t), that is required for Pi-ta-mediated signal recognition. A Pi
      ta-expressing susceptible mutant was identified using a genetic screen. Putative
      mutations at Ptr(t) do not alter recognition specificity to another resistance
      gene, Pi-k(s), in the Pi-ta homozygote, indicating that Ptr(t) is more likely
      specific to Pi-ta-mediated signal recognition. Genetic crosses of Pi-ta Ptr(t)
      and Pi-ta ptr(t) homozygotes suggest that Ptr(t) segregates as a single dominant
      nuclear gene. A ratio of 1:1 (resistant/susceptible) of a population of BC1 of Pi
      ta Ptr(t) with pi-ta ptr(t) homozygotes indicates that Pi-ta and Ptr(t) are
      linked and cosegregate. Genotyping of mutants of pi-ta ptr(t) and Pi-ta Ptr(t)
      homozygotes using ten simple sequence repeat markers at the Pi-ta region
      determined that Pi-ta and Ptr(t) are located within a 9-megabase region and are
      of indica origin. Identification of Ptr(t) is a significant advancement in
      studying Pi-ta-mediated signal recognition and transduction.

PMID- 18321186
TI  - Transcription of ENOD8 in Medicago truncatula nodules directs ENOD8 esterase to
      developing and mature symbiosomes.
AB  - In Medicago truncatula nodules, the soil bacterium Sinorhizobium meliloti reduces
      atmospheric dinitrogen into nitrogenous compounds that the legume uses for its
      own growth. In nitrogen-fixing nodules, each infected cell contains symbiosomes,
      which include the rhizobial cell, the symbiosome membrane surrounding it, and the
      matrix between the bacterium and the symbiosome membrane, termed the symbiosome
      space. Here, we describe the localization of ENOD8, a nodule-specific esterase.
      The onset of ENOD8 expression occurs at 4 to 5 days postinoculation, before the
      genes that support the nitrogen fixation capabilities of the nodule. Expression
      of an ENOD8 promoter-gusA fusion in nodulated hairy roots of composite
      transformed M. truncatula plants indicated that ENOD8 is expressed from the
      proximal end of interzone II to III to the proximal end of the nodules. Confocal
      immunomicroscopy using an ENOD8-specific antibody showed that the ENOD8 protein
      was detected in the same zones. ENOD8 protein was localized in the symbiosome
      membrane or symbiosome space around the bacteroids in the infected nodule cells.
      Immunoblot analysis of fractionated symbiosomes strongly suggested that ENOD8
      protein was found in the symbiosome membrane and symbiosome space, but not in the
      bacteroid. Determining the localization of ENOD8 protein in the symbiosome is a
      first step in understanding its role in symbiosome membrane and space during
      nodule formation and function.

PMID- 18321187
TI  - The rsmA-like gene rsmA(Xcc) of Xanthomonas campestris pv. campestris is involved
      in the control of various cellular processes, including pathogenesis.
AB  - RsmA is an RNA-binding protein functioning as a global post-transcriptional
      regulator of various cellular processes in bacteria and has been demonstrated to
      be an important virulence regulator in many animal bacterial pathogens. However,
      its function in other phytopathogenic bacteria is unclear, except for the Erwinia
      carotovora RsmA, which acts as a negative virulence regulator. In this work, we
      investigated the function of the rsmA-like gene, named rsmA(Xcc), of the
      phytopathogen Xanthomonas campestris pv. campestris. Deletion of rsmA(Xcc)
      resulted in complete loss of virulence on the host plant Chinese radish,
      hypersensitive response on the nonhost plant pepper ECW-10R, and motility on the
      surface of an agar plate. The rsmA(Xcc) mutant displayed a significant reduction
      in the production of extracellular amylase, endoglucanase, and polysaccharide,
      but a significant increase in intracellular glycogen accumulation and an enhanced
      bacterial aggregation and cell adhesion. Microarray hybridization and
      semiquantitative reverse-transcription polymerase chain reaction analysis showed
      that deletion of rsmA(Xcc) led to significantly reduced expression of genes
      encoding the type III secretion system (T3SS), T3SS-effectors, and the bacterial
      aggregate dispersing enzyme endo-beta-1,4-mannanase. These results suggest that
      rsmA(Xcc) is involved in the control of various cellular processes, including
      pathogenesis of X. campestris pv. campestris.

PMID- 18321188
TI  - Cyst nematode parasitism of Arabidopsis thaliana is inhibited by salicylic acid
      (SA) and elicits uncoupled SA-independent pathogenesis-related gene expression in
      roots.
AB  - Compatible plant-nematode interactions involve the formation of an elaborate
      feeding site within the host root that requires the evasion of plant defense
      mechanisms by the parasite. Little is known regarding plant defense signaling
      pathways that limit nematode parasitism during a compatible interaction.
      Therefore, we utilized Arabidopsis thaliana mutants perturbed in salicylic acid
      (SA) biosynthesis or signal transduction to investigate the role of SA in
      inhibiting parasitism by the beet cyst nematode Heterodera schachtii. We
      determined that SA-deficient mutants (sid2-1, pad4-1, and NahG) exhibited
      increased susceptibility to H. schachtii. In contrast, SA-treated wild-type
      plants showed decreased H. schachtii susceptibility. The npr1-2 and npr1-3
      mutants, which are impaired in SA signaling, also showed increased susceptibility
      to H. schachtii, whereas the npr1-suppressor mutation sni1 showed decreased
      susceptibility. Constitutive pathogenesis-related (PR) gene-expressing mutants
      (cpr1 and cpr6) did not show altered susceptibility to H. schachtii; however,
      constitutive PR gene expression was restricted to cpr1 shoots with wild-type
      levels of PR-1 transcript present in cpr1 roots. Furthermore, we determined that
      H. schachtii infection elicits SA-independent PR-2 and PR-5 induction in wild
      type roots, while PR-1 transcript and total SA levels remained unaltered. This
      was in contrast to shoots of infected plants where PR-1 transcript abundance and
      total SA levels were elevated. We conclude that SA acts via NPR1 to inhibit
      nematode parasitism which, in turn, is negatively regulated by SNI1. Our results
      show an inverse correlation between root basal PR-1 expression and plant
      susceptibility to H. schachtii and suggest that successful cyst nematode
      parasitism may involve a local suppression of SA signaling in roots.

PMID- 18321189
TI  - Gene expression profiling during asexual development of the late blight pathogen
      Phytophthora infestans reveals a highly dynamic transcriptome.
AB  - Much of the pathogenic success of Phytophthora infestans, the potato and tomato
      late blight agent, relies on its ability to generate from mycelia large amounts
      of sporangia, which release zoospores that encyst and form infection structures.
      To better understand these stages, Affymetrix GeneChips based on 15,650 unigenes
      were designed and used to profile the life cycle. Approximately half of P.
      infestans genes were found to exhibit significant differential expression between
      developmental transitions, with approximately (1)/(10) being stage-specific and
      most changes occurring during zoosporogenesis. Quantitative reverse-transcription
      polymerase chain reaction assays confirmed the robustness of the array results
      and showed that similar patterns of differential expression were obtained
      regardless of whether hyphae were from laboratory media or infected tomato.
      Differentially expressed genes encode potential cellular regulators, especially
      protein kinases; metabolic enzymes such as those involved in glycolysis,
      gluconeogenesis, or the biosynthesis of amino acids or lipids; regulators of DNA
      synthesis; structural proteins, including predicted flagellar proteins; and
      pathogenicity factors, including cell-wall-degrading enzymes, RXLR effector
      proteins, and enzymes protecting against plant defense responses. Curiously, some
      stage-specific transcripts do not appear to encode functional proteins. These
      findings reveal many new aspects of oomycete biology, as well as potential
      targets for crop protection chemicals.

PMID- 18321190
TI  - Two receptor-like genes, Vfa1 and Vfa2, confer resistance to the fungal pathogen
      Venturia inaequalis inciting apple scab disease.
AB  - The Vf locus, originating from the crabapple species Malus floribunda 821,
      confers resistance to five races of the fungal pathogen Venturia inaequalis, the
      causal agent of apple scab disease. Previously, a cluster of four receptor-like
      genes, Vfa1, Vfa2, Vfa3, and Vfa4, was identified within the Vf locus. Because
      the amino-acid sequence of Vfa3 is truncated, it was deemed nonfunctional. In
      this study, each of the three full-length Vfa genes was introduced into a plant
      cloning vector, pCAMBIA2301, and used for Agrobacterium-mediated transformation
      of two apple cultivars, Galaxy and McIntosh, to assess functionality of these
      genes and to characterize their roles in resistance to V. inaequalis. Transformed
      apple lines carrying each of Vfa1, Vfa2, or Vfa4 were developed, analyzed for the
      presence of the transgene using polymerase chain reaction and Southern blotting,
      and assayed for resistance to apple scab following inoculation with V.
      inaequalis. Transformed lines expressing Vfa4 were found to be susceptible to
      apple scab, whereas those expressing either Vfa1 or Vfa2 exhibited partial
      resistance to apple scab. Based on Western blot analysis as well as microscopic
      analysis of plant resistance reactions, the roles of Vfa1 and Vfa2 in apple scab
      disease resistance response are discussed.

PMID- 18321191
TI  - Host genes involved in nodulation preference in common bean (Phaseolus vulgaris)
      rhizobium etli symbiosis revealed by suppressive subtractive hybridization.
AB  - Common bean cultivars are nodulated preferentially by Rhizobium etli lineages
      from the same center of host diversification. Nodulation was found to be earlier
      and numerous in bean plants inoculated with the cognate strain. We predicted that
      analysis of transcripts at early stages of the interaction between host and
      rhizobium would identify plant genes that are most likely to be involved in this
      preferential nodulation. Therefore, we applied a suppressive subtractive
      hybridization approach in which cDNA from a Mesoamerican cultivar inoculated with
      either the more- or less-efficient strain of R. etli was used as the driver and
      the tester, respectively. Forty-one independent tentative consensus sequences
      (TCs) were obtained and classified into different functional categories. Of 11
      selected TCs, 9 were confirmed by quantitative reverse-transcriptase polymerase
      chain reaction. Two genes show high homology to previously characterized plant
      receptors. Two other upregulated genes encode for Rab11, a member of the small
      GTP-binding protein family, and HAP5, a subunit of the heterotrimeric CCAAT
      transcription factor. Interestingly, one of the TCs encodes for an isoflavone
      reductase, which may lead to earlier Nod factor production by specific strains of
      rhizobia. The transcript abundance of selected cDNAs also was found to be higher
      in mature nodules of the more efficient interaction. Small or no differences were
      observed when an Andean bean cultivar was inoculated with a cognate strain,
      suggesting involvement of these genes in the strain-specific response. The
      potential role of these genes in the early preferential symbiotic interaction is
      discussed.

PMID- 18321192
TI  - Genetic dissection defines the roles of elsinochrome Phytotoxin for fungal
      pathogenesis and conidiation of the citrus pathogen Elsinoe fawcettii.
AB  - Elsinochrome pigments produced by many phytopathogenic Elsinoe spp. are nonhost
      selective toxins which react with oxygen molecules after light activation to
      produce highly toxic reactive oxygen species. The structures and chemical
      properties of four derivatives are well known. However, the biological roles of
      elsinochromes in fungal pathogenesis are poorly understood. Many isolates of
      Elsinoe fawcettii causing citrus scab are able to produce elsinochromes under
      axenic conditions. In this article, we report the cloning, expression, and
      functional characterization of the polyketide synthase-encoding gene, EfPKS1,
      which we show is required for the production of elsinochromes and fungal
      pathogenesis. Targeted disruption of EfPKS1 in E.fawcettii completely abrogated
      elsinochrome production, drastically reduced conidiation, and significantly
      decreased lesion formation on rough lemon leaves. All mutant phenotypes were
      restored to the wild type in fungal strains expressing a functional copy of
      EfPKS1. Accumulation of the EfPKS1 transcript and elsinochromes by a wild-type
      strain appears to be coordinately regulated by light, nutrients, and pH. The
      results indicate that the product of EfPKS1 is involved in the biosynthesis of
      elsinochromes via a fungal polyketide pathway, and that elsinochromes play an
      important role in fungal pathogenesis.

PMID- 18321193
TI  - Functional characterization of a gene family encoding Polygalacturonases in
      Phytophthora parasitica.
AB  - Phytophthora parasitica is an oomycete plant pathogen that causes severe disease
      in a wide variety of plant species. In our previous study, we discovered a
      multigene family encoding endopolygalacturonases (endoPG) in Phytophthora
      parasitica. Here, we screened the genomic library of Phytophthora parasitica for
      the genes encoding endoPG named pppg2 through pppg10, and analyzed their
      functions. Results obtained by real-time quantitative reverse transcriptase
      polymerase chain reaction demonstrated that some of these genes are highly
      induced during plant infection, which suggests their important roles in the
      pathogenesis of Phytophthora parasitica. Analysis by in-gel activity assay of
      recombinant proteins obtained from Pichia pastoris indicated that each of these
      genes encodes a functional endoPG. Investigation of the function of pppg genes in
      planta by a Potato virus X agroinfection system in tobacco revealed that each
      pppg caused specific effects, varying from no symptoms to dwarfism, necrosis,
      leaf curl, silvery leaf, and cracks in leaf stalks. Appearance of these effects
      depends on the expression of a pppg protein with a normal active site in the
      apoplast. These results indicated that each pppg plays a distinct role in the
      decomposition of plant cell wall.

PMID- 18321194
TI  - A survey of the Pseudomonas syringae pv. tomato DC3000 type III secretion system
      effector repertoire reveals several effectors that are deleterious when expressed
      in Saccharomyces cerevisiae.
AB  - The injection of nearly 30 effector proteins by the type III secretion system
      underlies the ability of Pseudomonas syringae pv. tomato DC3000 to cause disease
      in tomato and other host plants. The search for effector functions is complicated
      by redundancy within the repertoire and by plant resistance (R)-gene sentinels,
      which may convert effector virulence activities into a monolithic defense
      response. On the premise that some effectors target universal eukaryotic
      processes and that yeast (Saccharomyces cerevisiae) lacks R genes, the DC3000
      effector repertoire was expressed in yeast. Of 27 effectors tested, HopAD1,
      HopAO1, HopD1, HopN1, and HopU1 were found to inhibit growth when expressed from
      a galactose-inducible GAL1 promoter, and HopAA1-1 and HopAM1 were found to cause
      cell death. Catalytic site mutations affecting the tyrosine phosphatase activity
      of HopAO1 and the cysteine protease activity of HopN1 prevented these effectors
      from inhibiting yeast growth. Expression of HopAA1-1, HopAM1, HopAD1, and HopAO1
      impaired respiration in yeast, as indicated by tests with ethanol glycerol
      selective media. HopAA1-1 colocalized with porin to yeast mitochondria and was
      shown to cause cell death in yeast and plants in a domain-dependent manner. These
      results support the use of yeast for the study of plant-pathogen effector
      repertoires.

PMID- 18321195
TI  - Pyrolidium dithiocarbamate prevents shockwave lithotripsy-induced renal injury
      through inhibition of nuclear factor-kappa B and inducible nitric oxide synthase
      activity in rats.
AB  - PURPOSE: Extracorporeal shockwave lithotripsy (SWL) is commonly used for
      treatment of renal stones. Free oxygen radicals are involved in the
      pathophysiology of renal injury due to SWL. We investigated the protective effect
      of pyrolidium dithiocarbamate (PDTC), an antioxidant and nuclear factor kappa-B
      (NFkappa-B) inhibitor, against renal injury. MATERIALS AND METHODS: Forty-eight
      rats were divided into three groups: group 1, controls; group 2, SWL (15 kW, 1500
      pulses); and group 3, SWL + pyrolidium dithiocarbamate (PDTC) (100 mg/kg/day
      given intraperitoneally 1 day before and 5 days after SWL). The rats were
      sacrificed and their kidneys were removed on days 7 and 35 after SWL. Samples
      were fixed in formaldehyde solution, and renal tissues were examined for proximal
      tubular injury under light microscopy. iNOS activity and active subunit of
      NFkappa-B, p65, were evaluated immunohistochemically using rat monoclonal
      antibodies interpreting results semiquantitatively. RESULTS: There were
      significant differences between SWL and control groups on days 7 and 35,
      considering histological changes under light microscope (p < 0.02). There was
      significant decrease in necrosis and fibrosis in PDTC group compared to SWL
      group. Expression of inducible nitric oxide synthase (iNOS) and p65 on days 7 and
      35 were at basal levels as seen with immunohistochemical staining. There were
      high concentrations of iNOS and p65 in the SWL group (P < 0.02). No significant
      difference in concentrations was seen between the control and the PDTC groups (P
      > 0.02). CONCLUSION: We found that curcumin decreased the expression of iNOS,
      p65, and serum nitric oxide levels, and helped prevent interstitial, glomerular,
      tubular epithelial, and endothelial cellular injury. We believe that PDTC could
      be used, particularly in high-risk patients, as a protective agent against renal
      injury due to SWL.

PMID- 18321196
TI  - Relationship between calorie restriction and the biological clock: lessons from
      long-lived transgenic mice.
AB  - The master clock located in the brain regulates circadian rhythms in mammals.
      Similar clocks are found in peripheral tissues. Life span has been independently
      increased by reset circadian rhythms and caloric restriction (CR). The mechanisms
      by which CR extends life span are not well understood. We found that alphaMUPA
      transgenic mice that exhibit reduced eating and live longer show high amplitude,
      appropriately reset circadian rhythms in clock gene expression, and clock
      controlled output systems, such as feeding time and body temperature. As CR
      resets circadian rhythms, and the circadian clock controls many physiological and
      biochemical systems, we suggest that the biological clock could be an important
      mediator of longevity in calorically restricted animals.

PMID- 18321197
TI  - Scientific justification of cryonics practice.
AB  - Very low temperatures create conditions that can preserve tissue for centuries,
      possibly including the neurological basis of the human mind. Through a process
      called vitrification, brain tissue can be cooled to cryogenic temperatures
      without ice formation. Damage associated with this process is theoretically
      reversible in the same sense that rejuvenation is theoretically possible by
      specific foreseeable technology. Injury to the brain due to stopped blood flow is
      now known to result from a complex series of processes that take much longer to
      run to completion than the 6 min limit of ordinary resuscitation technology.
      Reperfusion beyond the 6 min limit primarily damages blood vessels rather than
      brain tissue. Apoptosis of neurons takes many hours. This creates a window of
      opportunity between legal death and irretrievable loss of life for human and
      animal subjects for cryopreservation with possibility of future resuscitation.
      Under ideal conditions, the time interval between onset of clinical death and
      beginning of cryonics procedures can be reduced to less than 1 min, but much
      longer delays could also be compatible with ultimate survival. Although the
      evidence that cryonics may work is indirect, the application of indirect evidence
      is essential in many areas of science. If complex changes due to aging are
      reversible at some future date, then similarly complex changes due to stopped
      blood flow and cryopreservation may also be reversible, with life-saving results
      for anyone with medical needs that exceed current capabilities.

PMID- 18321198
TI  - Preliminary study of the effect of FK506 nanospheric-suspension eye drops on
      rejection of penetrating keratoplasty.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of a topical FK506
      nanospheric suspension in a rat model of penetrating keratoplasty. METHODS: FK506
      nanospheres were prepared by using a biodegradable poly (lactic-co-glycolic acid)
      copolymer (PLGA). Its distribution in the eye and blood after a single
      instillation was examined in rabbits. Sprague-Dawley (SD) rats received corneal
      heterografts and were topically treated with phosphate-buffered saline (PBS),
      PLGA, FK-506 0.01% (nanospheres), or dexamethasone 0.05% solutions twice a day
      for 28 days. Rejection index and graft-survival time were recorded and compared
      between the four groups. Three grafts were collected at different time points for
      immunohistochemical studies. RESULTS: In the cornea, the FK-506 concentration
      reached its peak within 1 h of a single eye-drop instillation and then decreased
      by half (1667.85 +/- 611.87 ng/g) at 8 h. FK-506 cannot be detected in rabbit
      blood. There were significant differences in the graft-survival time between the
      FK-506 nanosphere group (15.09 +/- 4.81 days) and the other three groups [PBS
      (7.90 +/- 1.20, t = -4.594, P < 0.001), PLGA (8.44 +/- 0.88, t = - 4.074, P =
      0.001) and dexamethasone (10.44 +/- 1.42, t = -2.790, P = 0.012)]. The rejected
      corneas in the FK506 nanosphere group showed significantly fewer CD4, CD8, CD68,
      CD79, vascular endothelial growth factor, ICAM, and tumor growth factor-beta(1)
      positive cells than those in the other groups. CONCLUSIONS: FK506 0.01%
      nanospheric-suspension eye drops delayed the occurrence of corneal allograft
      rejection and prolonged allograft survival time. The FK506 nanospheres may be
      valuable in suppressing corneal graft rejection.

PMID- 18321199
TI  - Successful treatment of postoperative fungal endophthalmitis using intravitreal
      and intracameral voriconazole.
AB  - AIM: The aim of this study was to describe 3 cases of postoperative fungal
      endophthalmitis successfully treated with anterior chamber washout, pars plana
      vitrectomy, and intracameral and intravitreal voriconazole injection. RESULTS:
      Three (3) patients from a single retina center in India developed culture-proven
      fungal endophthalmitis after cataract surgery in 1 eye. All patients underwent
      anterior chamber washout, pars plana vitrectomy, and intracameral and
      intravitreal voriconazole injections intraoperatively. All cases demonstrated
      substantial improvement in vision and intraocular inflammation after surgery.
      CONCLUSIONS: The combination of anterior chamber washout, pars plana vitrectomy,
      and intracameral and intravitreal voriconazole injection is a viable therapeutic
      option in cases of fungal endophthalmitis.

PMID- 18321200
TI  - Mycophenolate mofetil in the treatment of ocular inflammation in ANCA-associated
      vasculitis.
AB  - AIM: The aim of this study was to describe the use of mycophenolate mofetil (MMF)
      in the treatment of patients with antineutrophil cytoplasmic antibody (ANCA)
      associated vasculitis with ocular involvement. METHODS: A retrospective review
      was performed. Ocular and systemic manifestations, history of previous
      immunosuppressive drug therapy, concurrent therapy with MMF, response to
      treatment, side effects related to the use of MMF, and follow-up period were
      recorded. RESULTS: Nine (9) eyes of 5 patients were evaluated. Ocular involvement
      included scleritis, choroidal and orbital granuloma, multifocal choroiditis,
      intermediate uveitis, and lacrimal gland involvement. Mycophenolate was started
      at 2 g daily. Mean follow-up after the initiation of MMF was 36 months. Mean
      prednisolone dose at onset of treatment with MMF was 27 mg daily and was reduced
      to 7 mg daily as disease control was achieved. Visual acuity was maintained or
      improved in all eyes, apart from 1 eye, which developed cataract formation. One
      (1) patient required a reduction in the dose of mycophenolate owing to diarrhea.
      CONCLUSIONS: Our study suggests that mycophenolate mofetil may be a safe,
      effective therapeutic modality for ocular inflammation associated with ANCA
      associated vasculitis.

PMID- 18321202
TI  - Targeting reactive oxygen species in hypertension.
AB  - Oxidative stress plays an important role in the pathogenesis of hypertension. A
      number of sources of reactive oxygen species have been identified including NADPH
      oxidase, endothelial NO synthase, and xanthine oxidase. Inhibitors of these
      systems reduce blood pressure in experimental models. Targeted overexpression of
      antioxidant systems and interference with expression of oxidant systems has also
      been successfully used in animal models of hypertension. It is expected that
      these strategies will eventually be translated to human disease, but currently,
      the specificity and toxicity of such measures are not yet fulfilling quality
      criteria for treatment of humans. In the meantime, presumably nontoxic measures,
      such as administration of antioxidant vitamins, are the only available treatments
      for oxidative stress in humans. In this review, we discuss strategies to target
      oxidative stress both in experimental models and in humans. We also discuss how
      patients could be selected who particularly benefit from antioxidant treatment.
      In clinical practice, diagnostic procedures beyond measurement of blood pressure
      will be necessary to predict the response to antioxidants; these procedures will
      include measurement of antioxidant status and detailed assessment of vascular
      structure and function.

PMID- 18321201
TI  - Redox signaling, vascular function, and hypertension.
AB  - Accumulating evidence supports the importance of redox signaling in the
      pathogenesis and progression of hypertension. Redox signaling is implicated in
      many different physiological and pathological processes in the vasculature. High
      blood pressure is in part determined by elevated total peripheral vascular
      resistance, which is ascribed to dysregulation of vasomotor function and
      structural remodeling of blood vessels. Aberrant redox signaling, usually induced
      by excessive production of reactive oxygen species (ROS) and/or by decreases in
      antioxidant activity, can induce alteration of vascular function. ROS increase
      vascular tone by influencing the regulatory role of endothelium and by direct
      effects on the contractility of vascular smooth muscle. ROS contribute to
      vascular remodeling by influencing phenotype modulation of vascular smooth muscle
      cells, aberrant growth and death of vascular cells, cell migration, and
      extracellular matrix (ECM) reorganization. Thus, there are diverse roles of the
      vascular redox system in hypertension, suggesting that the complexity of redox
      signaling in distinct spatial spectrums should be considered for a better
      understanding of hypertension.

PMID- 18321203
TI  - Antimicrobial resistance of Campylobacter spp. isolated from broiler flocks in
      Iceland 2001-2005.
AB  - Minimum inhibitory concentrations of six antimicrobial agents were determined for
      one Campylobacter sp. isolate from each of the 362 Campylobacter-positive
      commercial chicken flocks in Iceland in the years 2001-2005. Of all isolates
      tested, 6.9% were resistant, although none were multiresistant. Resistance to
      ampicillin was most commonly observed (3.6%) followed by resistance to
      enrofloxacin (3%), nalidixic acid (1.9%), and oxytetracyclin (0.3%), with cross
      resistance between enrofloxacin and nalidixic acid. All isolates were susceptible
      to erythromycin and gentamicin. Resistance rates among Campylobacter coli
      isolates (7/13 or 53.8%) were much higher than among Campylobacter jejuni
      isolates (18/349 or 5.2%), and resistance patterns differed. Resistant strains
      were compared using pulsed field gel electrophoresis. Macrorestriction with SmaI
      and KpnI restriction enzymes yielded 13 different pulsotypes, none of which
      indicated a predominant genotype. Specific pulsotypes with uniform resistance
      patterns arising on geographically separated farms indicate clonal dissemination.
      Although resistance levels were low and similar to that seen in the other Nordic
      countries, further research on this matter is needed as there is no antimicrobial
      selective pressure in chicken farming in Iceland.

PMID- 18321204
TI  - Class I integron-borne bla(VIM-1) carbapenemase in a strain of Enterobacter
      cloacae responsible for a case of fatal pneumonia.
AB  - We report here a fatal case of nosocomial pneumonia due to a multidrug-resistant
      (MDR) strain of Enterobacter cloacae, which was also resistant to carbapenems, in
      a patient with a diagnosis of Churg-Strauss syndrome. The microorganism was
      investigated for the presence of metallo- and extended-spectrum beta-lactamases.
      The strain produced two class 1 integrons carrying bla(VIM-1) and aadA2 gene
      cassettes located on chromosomal and plasmidic DNA, respectively, and a plasmid
      encoded SHV-12 extended-spectrum beta-lactamase. Our results clearly demonstrate
      the transfer of this kind of resistance in E. cloacae with potentially serious
      clinical implications.

PMID- 18321205
TI  - Assessment of efflux pump gene expression in a clinical isolate Mycobacterium
      tuberculosis by real-time reverse transcription PCR.
AB  - The importance of some putative efflux pumps in conferring drug resistance on
      certain strain of Mycobacterium tuberculosis was determined by using multidrug
      resistant (MDR) strain 1499 bearing defined mutations in rpoB and katG. The
      clinical isolate 1499 was tested for drug sensitivity and expression level of
      five putative efflux pump genes by real-time RT-PCR. In the presence of
      rifampicin or isoniazid, this isolate showed increased transcription of putative
      efflux pump genes Rv1258c and Rv1410c. Rv1819c was overexpressed only upon
      isoniazid exposure (p<0.05). Overexpression of some efflux genes is associated
      with multidrug resistance in certain clinical isolate of M. tuberculosis.

PMID- 18321206
TI  - Characterization of Salmonella enterica serovar Agona slaughter isolates from the
      animal arm of the National Antimicrobial Resistance Monitoring System-Enteric
      Bacteria (NARMS): 1997 through 2003.
AB  - A total of 499 Salmonella enterica serovar Agona isolates from cattle, swine,
      chicken, and turkey samples were assayed for antimicrobial susceptibility and
      subtyped using pulsed-field gel electrophoresis (PFGE). Salmonella Agona isolates
      exhibited increased resistance to amoxicillin/clavulanic acid, ampicillin,
      cefoxitin, ceftiofur, cephalothin, and chloramphenicol, and a single isolate was
      resistant to ceftriaxone. Multiple drug resistance (MDR; resistance >or= 2
      antimicrobials) was exhibited in 57% (n=282/499) of the Salmonella Agona isolates
      and 22% (n=111/499) of these Salmonella Agona isolates were resistant to five or
      more antimicrobials. PFGE patterns of 482 Salmonella Agona slaughter samples
      resulted in 165 unique patterns. Cluster analysis indicated that isolates
      indistinguishable by PFGE appeared to group according to antimicrobial resistance
      profiles. These data suggest that Salmonella Agona is increasing in prevalence in
      U.S. cattle presented for slaughter and should be further monitored.

PMID- 18321207
TI  - Alterations of porin, pumps, and penicillin-binding proteins in carbapenem
      resistant clinical isolates of Pseudomonas aeruginosa.
AB  - Carbapenem-resistant clinical isolates of Pseudomonas aeruginosa from Sweden and
      Norway (n=27) were characterized regarding transcription of genes encoding OprD,
      efflux pumps MexAB-OprM and MexCD-OprJ, as well as penicillin-binding proteins
      (PBP) 2 and 3. Quantification of mRNA was performed with real-time RT-PCR. Levels
      of mRNA in clinical isolates were compared to ATCC 27853 and average
      transcription levels of four carbapenem-susceptible clinical isolates of P.
      aeruginosa. Sequencing of oprD, pbp 2, and pbp 3 was performed in selected
      isolates. An efflux inhibition assay was performed with Phe-Arg-beta
      naphtylamide. Most carbapenem-resistant isolates had decreased levels of oprD
      mRNA. Among six isolates with normal amount of oprD mRNA, half of them had
      significant OprD sequence alterations. Increased transcription of mexB was
      observed in 16 of 23 meropenem-resistant isolates, and one isolate showed mexD
      hyperproduction. Decreased amount of pbp 2 and pbp 3 was found in two and three
      isolates, respectively. Sequencing of pbp 2 and 3 revealed no amino acid changes
      potentially leading to conformational changes. In conclusion, OprD changes were
      the predominant mechanism of high-level carbapenem resistance, and increased
      transcription of mexB was often present in meropenem-resistant isolates. Reduced
      transcription of pbp 2 and 3 may contribute to the carbapenem resistance.

PMID- 18321208
TI  - Mechanisms of antibiotic resistance in Escherichia coli isolates recovered from
      wild animals.
AB  - Seventy-two fecal samples obtained from wild animals in Portugal were sampled on
      Levine agar plates (non-supplemented with antibiotics), and Escherichia coli
      isolates were recovered from 56 of them (78%), obtaining a total of 112 E. coli
      isolates (two per sample). Susceptibility to 16 antibiotics was studied in these
      isolates, and the following percentages of resistance were obtained:
      tetracycline, streptomycin, ampicillin, and trimethoprim-sulfamethoxazole (SXT)
      (range 19-35%); nalidixic acid (14%); ciprofloxacin (9%); amoxicillin-clavulanic
      acid, gentamicin, tobramycin, and chloramphenicol (range 4.5-7%); cefotaxime, and
      aztreonam (1.8%); ceftazidime (0.9%); and amikacin, cefoxitin, and imipenem (0%).
      A bla(TEM) gene was found in 22 of the 25 ampicillin-resistant isolates, and the
      gene encoding CTX-M-14 beta-lactamase was identified in the two cefotaxime
      resistant isolates (recovered from a common kestrel and a sparrowhawk),
      associated with bla(TEM-52) gene in one of them. Other resistance genes detected
      were as follows: aac(3)-II or aac(3)-IV genes in all gentamicin-resistant
      isolates; aadA1 or aadA2 in 22 of 25 streptomycin-resistant isolates; tet(A)
      and/or tet(B) in all 39 tetracycline-resistant isolates; and sul1 and/or sul2
      and/or sul3 genes in all 21 SXT-resistant isolates. Two amino acid changes in
      GyrA protein (Ser83Leu + Asp87Asn) and one change in ParC protein (Ser80Ile) were
      identified in all 10 ciprofloxacin-resistant isolates of our series. The
      intestinal tract of wild animals is a reservoir of antibiotic resistance genes,
      especially for ampicillin, tetracycline, streptomycin, and SXT, and it is also
      remarkable that multiresistant E. coli isolates are detected in some of the
      tested animals.

PMID- 18321209
TI  - Nitric oxide, tetrahydrobiopterin, oxidative stress, and endothelial dysfunction
      in hypertension.
AB  - Endothelial dysfunction in the setting of cardiovascular risk factors such as
      hypercholesterolemia, diabetes mellitus, chronic smoking, as well hypertension,
      is, at least in part, dependent of the production of reactive oxygen species
      (ROS) and the subsequent decrease in vascular bioavailability of nitric oxide
      (NO). ROS-producing enzymes involved in increased oxidative stress within
      vascular tissue include NADPH oxidase, xanthine oxidase, and mitochondrial
      superoxide producing enzymes. Superoxide produced by the NADPH oxidase may react
      with NO, thereby stimulating the production of the NO/superoxide reaction product
      peroxynitrite. Peroxynitrite in turn has been shown to uncouple eNOS, therefore
      switching an antiatherosclerotic NO producing enzyme to an enzyme that may
      accelerate the atherosclerotic process by producing superoxide. Increased
      oxidative stress in the vasculature, however, is not restricted to the
      endothelium and also occurs within the smooth muscle cell layer. Increased
      superoxide production has important consequences with respect to signaling by the
      soluble guanylate cyclase and the cGMP-dependent kinase I, which activity and
      expression is regulated in a redox-sensitive fashion. The present review will
      summarize current concepts concerning eNOS uncoupling, with special focus on the
      role of tetrahydrobiopterin in mediating eNOS uncoupling.

PMID- 18321226
TI  - The future of obesity: new drugs versus lifestyle interventions.
AB  - BACKGROUND: Obesity causes serious medical complications and impairs quality of
      life. However, its management remains challenging. OBJECTIVE: To assist health
      professionals who counsel patients who are overweight or obese by discussing the
      possible add-on value of new drugs over lifestyle interventions. METHODS: A
      critical analysis is made of the available evidence of the long-term efficacy of
      diet and exercise and/or anti-obesity agents such as orlistat, sibutramine and
      rimonabant. RESULTS/CONCLUSION: Lifestyle interventions remain the cornerstone of
      the treatment of obesity, but adherence is poor and long-term success is modest.
      Pharmacological agents may be useful adjuncts for improving weight loss and
      maintenance, and health outcomes, and should be continued in good responders.
      Drug therapy and lifestyle intervention are not opponent strategies, but should
      probably be combined to tackle obesity.

PMID- 18321227
TI  - Discontinued drugs in 2006: oncology drugs.
AB  - This perspective is the last in a series of papers discussing drugs dropped from
      clinical development in 2006. Specifically, this paper focuses on the 16 drugs
      discontinued for the treatment of cancer, the largest area of pharma R&D. This
      was based on a search of the Pharmaprojects database for drugs reaching Phase I
      III clinical trials.

PMID- 18321228
TI  - Novel beta-lactam antibiotics and inhibitor combinations.
AB  - BACKGROUND: beta-Lactam antibiotics are the most used antibacterial agents in
      clinical practice, but the development of resistance poses some questions about
      their future leading to an urgent requirement for new compounds. Specifically,
      beta-lactamases represent the commonest single cause of bacterial resistance to
      beta-lactam antibiotics. Numerous chromosomal and plasmid-mediated types are
      known and classified on the basis of their structure. Among them, extended
      spectrum beta-lactamases (ESBLs) and AmpC beta-lactamase can confer broad
      spectrum antibiotic resistance to ureidopenicillins, third-generation
      cephalosporins and aztreonam, posing unique therapeutic challenges. Furthermore,
      the spreading emergence of carbapenemases is a significant threat to the
      management of nosocomial infections. OBJECTIVE: To review characteristics of new
      drugs for beta-lactam resistance. METHODS: We reviewed the principal
      characteristics of the new drugs studied for overcoming the emergence of beta
      lactam resistance among Gram-negative and Gram-positive pathogens.
      RESULTS/CONCLUSIONS: We included in our review new beta-lactamase inhibitors (Ro
      48-1220), non-beta-lactam compounds (NXL-104), new oxapenenems (AM-112, -113, 
      114, -115) and penems (faropenem), new cephalosporins (ceftobiprole and
      ceftaroline) and new carbapenems (doripenem).

PMID- 18321229
TI  - New antibacterial agents for treating infections caused by multi-drug resistant
      Gram-negative bacteria.
AB  - BACKGROUND: Infections caused by multi-drug resistant (MDR) Gram-negative
      bacteria represent an ever-growing area of unmet medical need. To address this
      need, it is imperative that novel classes of antibiotics demonstrating activity
      against bacterial strains resistant to established antibiotics are introduced
      into the clinic. OBJECTIVES: To examine the current status of the Gram-negative
      antibacterial pipeline, ranging from the more advanced preclinical candidates to
      drugs recently launched, and look to the future of anti-Gram-negative drug
      development. METHODS: Information was compiled from scientific and patent
      literature, conference proceedings and company publications/websites.
      RESULTS/CONCLUSIONS: None of the antibacterial agents currently in clinical
      trials that encompass Gram-negative bacteria in their spectrum of activity
      possess sufficiently novel modes of action to circumvent extant antibiotic
      resistance mechanisms. Furthermore, although some interesting anti-Gram-negative
      drug candidates are nearing the beginning of clinical trials, they are limited in
      number and, even in the best-case scenario, many years away from the clinic.

PMID- 18321230
TI  - The emerging field of HCV drug resistance.
AB  - BACKGROUND: With 170 million people infected worldwide and an inadequate current
      standard of care, hepatitis C virus (HCV) infection represents a major unmet
      medical need. Multiple companies are working on the discovery and development of
      specific HCV antiviral drugs, including inhibitors of HCV polymerase, protease
      and NS5A. Because of the error-prone nature of viral RNA replication, resistance
      mutants will develop that could present a potentially significant challenge to
      developing antiviral treatment regimens. OBJECTIVE: Here, we review the major
      drug classes currently in preclinical and clinical development and the resistance
      mutations specific for each class that have been identified from cell culture
      and/or in vivo studies. METHODS: We have analyzed currently available scientific
      literature to create a comprehensive review of the current state of the art in
      the field of HCV resistance to specific antiviral agents, in vitro and in vivo.
      RESULTS/CONCLUSION: Most specific HCV inhibitors described in the literature can
      select resistant viral variants in cell culture and in the clinic. Interplay of a
      mutant's fitness and its level of resistance will determine its clinical
      importance. Combinations of non-cross-resistant classes of drugs will be key to
      successful antiviral therapy. The number of drugs in a combination as well as the
      optimal duration of antiviral treatment, are important issues that need to be
      addressed in future studies.

PMID- 18321231
TI  - Development of anti-obesity agents: drugs that target neuropeptide and
      neurotransmitter systems.
AB  - BACKGROUND: Obesity results from an imbalance of energy intake and energy
      expenditure. While the prevalence of obesity is increasing and the negative
      impact on public health is being recognized, highly effective and safe therapy
      for obesity is not yet available. OBJECTIVE: This review summarizes the current
      state of the art in the late-stage development area of anti-obesity drugs,
      provides a framework for understanding the potential disparity of animal data and
      human disease modification for some agents, and highlights novel agents that may
      provide significant clinical benefits in the future. METHODS: Published
      literature and meeting proceedings were surveyed to review the late-stage
      development of new anti-obesity agents. RESULTS/CONCLUSIONS: Most of the current
      clinical candidates for obesity treatment are targeting neurotransmitter
      receptors or peptide receptors. While new agents have been discovered, a
      significant failure rate also emerged. Rigorous scientific investigations,
      developing target engagement tools, and understanding any potential rodent versus
      human species difference will be necessary to ascertain mechanism-based efficacy
      and increase the probability of success.

PMID- 18321232
TI  - Vaspin: a novel serpin with insulin-sensitizing effects.
AB  - BACKGROUND: A variety of substances, including free fatty acids, leptin, tumor
      necrosis factor-alpha, acylation-stimulating protein, adiponectin, and resistin,
      are secreted by adipocytes. They modulate insulin sensitivity and are new
      therapeutic targets in metabolic syndrome. OBJECTIVE: To identify novel
      adipokines derived from visceral adipose tissues. METHOD: We used the PCR-based
      cDNA subtraction method to screen the genes predominantly expressed in visceral
      white adipose tissues (WATs) in Otsuka Long-Evans Tokushima fatty (OLETF) rats,
      an animal model of abdominal obesity and type 2 diabetes. RESULTS/CONCLUSIONS: We
      identified the vaspin gene (Serpina12) which is upregulated in visceral WATs of
      OLETF rats. Vaspin mRNA was barely detectable at 6 weeks of age and it was
      abundantly and exclusively expressed in visceral WATs at 30 weeks of age, when
      OLETF rats reach their peak body weight. However, vaspin mRNA decreased with
      worsening of diabetes and body weight loss. Vaspin mRNA increased with treatment
      of thiazolidinediones (pioglitazone). Administration of recombinant vaspin into
      high-fat high-sucrose chow-induced obese ICR mice improved glucose tolerance and
      insulin sensitivity. Vaspin may be the compensatory molecule in the pathogenesis
      of metabolic syndrome and vaspin recombinant protein or vaspin-mimicking agents
      such as vaspin analogs, antibodies or small molecule agents may be the link to
      drug discovery and development.

PMID- 18321233
TI  - New taxanes in development.
AB  - BACKGROUND: Taxanes are presently widely employed for the medical treatment of
      cancer. However, despite the huge clinical success, these agents exhibit clinical
      problems related to poor drug solubility, toxicity and, in particular, drug
      resistance. OBJECTIVE: To identify the critical points related to the process of
      development of novel taxanes. METHODS: Publicly available data on the paclitaxel
      and docetaxel analogues, which have entered a clinical development phase in the
      last 2 years have been taken into consideration. The development involved novel
      formulations of paclitaxel and novel chemical entities. For each agent in each
      category the development phase is analysed and a synthetic comment for each
      category is included. RESULTS/CONCLUSIONS: Despite all the efforts, until now
      clinical success with the new development of taxanes has been limited. Moreover,
      the expected clinical introduction of epothilones could further restrict the
      space for development of novel taxanes. Despite these facts, some interesting
      concepts emerged during the process of development and could lead to successful
      drugs in the forthcoming years.

PMID- 18321234
TI  - The future of the IL-1 receptor antagonist anakinra: from rheumatoid arthritis to
      adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis.
AB  - BACKGROUND: IL-1 receptor antagonist (IL-1Ra) is a naturally occurring IL-1RI
      binding molecule that blocks the biologic effects of the proinflammatory cytokine
      IL-1. A recombinant form of human IL-1Ra, anakinra (Kineret), has been approved
      for use in rheumatology initially to manage rheumatoid arthritis (RA) patients
      that are refractory to more conventional forms of treatment. OBJECTIVE: This
      review summarizes the experience with anakinra in the treatment of patients with
      rheumatic diseases emphasizing its beneficial effects in novel applications.
      METHODS: English-language trials of anakinra were searched using MEDLINE and
      abstracts from rheumatology scientific meetings. RESULTS/CONCLUSIONS: In the
      treatment of patients with RA anakinra is effective but inferior to TNF-alpha
      blocking agents. Over the last few years it has become increasingly evident that
      anakinra is highly effective and safe in patients with systemic-onset juvenile
      idiopathic arthritis, adult-onset Still's disease, hereditary autoinflammatory
      syndromes, Schnitzler's syndrome and recently in gouty attacks.

PMID- 18321235
TI  - Brivaracetam: a new drug in development for epilepsy and neuropathic pain.
AB  - BACKGROUND: Epilepsy is a neurological disorder with a worldwide prevalence
      estimated to be 0.5-1.0% of the population. Many potent antiepileptic drugs (AED)
      have been used for treatment but still about 30% of patients are resistant to
      current AEDs. Some AEDs are also used for the treatment of neuropathic pain.
      OBJECTIVE: The aim of this report is to present preclinical and clinical studies
      of brivaracetam (UCB-34714), a new drug developed by UCB Pharma. METHODS:
      Published results of preclinical studies in several animal models of epilepsy,
      neuropathic pain, essential tremor and results of Phase I and II evaluations of
      brivaracetam have been analysed. RESULTS/CONCLUSION: Brivaracetam represents a
      new mechanism of action being a ligand of synaptic vesicle protein 2A. It is
      undergoing Phase III evaluation after a successful Phase II programme in which
      was effective as an adjunctive treatment in partial-onset epilepsy (50 mg/day).
      It is well tolerated, without serious adverse side effects.

PMID- 18321236
TI  - Novel therapies targeting the immune system: CTLA4 blockade with tremelimumab (CP
      675,206), a fully human monoclonal antibody.
AB  - BACKGROUND: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) is an activation
      induced transmembrane receptor. Binding of CTLA4 to its natural ligands
      downregulates T-cell activation. Tremelimumab, a fully human IgG(2) monoclonal
      antibody binds CTLA4 and prevents ligand interaction resulting in enhanced
      cellular immunity. OBJECTIVE: To provide a comprehensive overview of the
      preclinical and clinical studies conducted during the development of
      tremelimumab. METHODS: Data with tremelimumab from all relevant preclinical
      studies and clinical trials completed at the time of publication and submitted to
      scientific meetings or published in peer-reviewed journals were collected and
      analysed. Salient clinical aspects observed during its early development were
      also included. RESULTS/CONCLUSIONS: CTLA4 blockade with tremelimumab at 15 mg/kg
      every 3 months has demonstrated substantial antitumor activity and an overall
      safe profile in patients with advanced melanoma. Phase III studies in melanoma
      and earlier stages of clinical development in colorectal, pancreatic, breast, and
      non-small cell lung carcinomas are ongoing.

PMID- 18321237
TI  - Use of cethromycin, a new ketolide, for treatment of community-acquired
      respiratory infections.
AB  - BACKGROUND: The ketolides are a subclass of macrolides, which were designed
      specifically to overcome macrolide-resistant respiratory pathogens. Ketolides
      lack the cladinose sugar, which is replaced with a 3-ketone group. Ketolides bind
      to a secondary region on domain II of the 23S rRNA subunit. Telithromycin was the
      first ketolide to be approved by the FDA in 2004 for treatment of community
      acquired pneumonia (CAP), acute exacerbations of chronic bronchitis (AECB) and
      sinusitis. However, in 2006, after reports of serious hepatotoxicity, the FDA
      issued a public health advisory followed by a warning. In 2007 the indications
      for treatment of AECB and sinusitis were removed from the labeling. Cethromycin
      (ABT-773) is the only other ketolide currently under clinical development.
      OBJECTIVE: To review currently available data on cethromycin, including
      chemistry, in vitro activity, pharmacokinetics, pharmacodynamics, in vivo
      activity and results of treatment studies in humans. METHODS: A search was made
      in PubMed, pharmaceutical databases and meeting abstracts using the terms
      ketolides, ABT-773 and cethromycin. RESULTS/CONCLUSIONS: Cethromycin has
      comparable tissue penetration, pharmacokinetics and in vitro activity compared
      with telithromycin to Streptococcus pneumoniae, including multidrug-resistant
      isolates, Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila
      pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila. There is only one
      published CAP treatment study that compared cethromycin 150 mg q.d. with 150 mg
      b.i.d. One Phase II and a Phase II/III study have been presented in abstract
      form, both were non-comparative, dose-ranging studies, which suggested that 150
      mg q.d. or 300 mg q.d. were comparable in terms of clinical response and
      bacterial eradication, although data on the latter are limited. Data on side
      effects are limited and appear to be mainly gastrointestinal. There have been no
      reports of serious hepatotoxicity at the time of this writing. Cethromycin may
      have other uses in addition to treatment of CAP respiratory infections, including
      treatment of infections due to Neisseria gonorrhoeae and Chlamydia trachomatis
      and bioterrorism agents including Bacillus anthracis, Yersinia pestis and
      Francisella tularensis.

PMID- 18321238
TI  - The role of gefitinib in the management of Asian patients with non-small cell
      lung cancer.
AB  - BACKGROUND: Lung cancer is the most common cause of death in cancer patients
      worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of
      lung cancer cases. The prognosis of NSCLC is still poor, albeit slow and steady
      improvement achieved in the past three decades by chemotherapy. Recently, the
      importance of epidermal growth factor receptor (EGFR) in the pathogenesis and
      progression in NSCLC was identified particularly in those cancer cells with EGFR
      mutation and/or increased gene copy number. Gefitinib was the first EGFR tyrosine
      kinase inhibitor approved for treating advanced NSCLC [corrected] It has become a
      popular choice in treating Asian patients after a higher response rate was
      reported in Japanese patients than in non-Japanese patients in the first Phase II
      trial. OBJECTIVE: To evaluate the role of gefitinib in the treatment of Asian
      patients with NSCLC. METHODS: A review of published papers in PubMed and Embase
      (2000-2007) and meeting reports of the American Society of Clinical Oncology and
      World Conference on Lung Cancer (2000-2007) was carried out. RESULTS/CONCLUSIONS:
      In general, gefitinib is well tolerated. As the second- or third-line treatment,
      gefitinib has proven survival benefits in Asian patients with advanced NSCLC,
      when compared with placebo. It has equivalent efficacy to docetaxel with less
      toxicity as the second-line therapy. As the first-line therapy, it yielded
      encouraging results but its final role is pending on the results of the ongoing
      randomised Phase III trial. Gefitinib should be considered as the treatment of
      choice for second- or third-line therapy in advanced NSCLC in Asian patients
      after progression from previous chemotherapy. Its role as the first-line,
      adjuvant or neoadjuvant therapy remains to be determined.

PMID- 18321239
TI  - Raltegravir: an integrase inhibitor for HIV-1.
AB  - BACKGROUND: The need to develop antiretroviral agents with novel mechanisms of
      action persists for the treatment of both antiretroviral- experienced and
      antiretroviral-naive patients with HIV/AIDS. This is mandated, in part, by the
      perpetual advent of antiretroviral-resistant HIV-1 strains. Raltegravir has been
      shown to specifically inhibit the essential, HIV-1-encoded, integrase enzyme. As
      a result, this agent represents a promising chemotherapeutic agent for the
      treatment of HIV/AIDS. OBJECTIVE: To form an evidence-based determination of the
      clinical efficacy, pharmacokinetics and safety profile of raltegravir. METHOD: We
      discuss available peer-reviewed publications, preliminary data presented in
      abstract from relevant scientific meetings and data available from the US Food
      and Drug Administration (FDA). RESULTS/CONCLUSION: Current evidence strongly
      supports raltegravir use in highly active antiretroviral therapy (HAART) regimens
      constructed to treat patients failing current therapies with multi-drug-resistant
      HIV-1. Additional data are needed to determine its role in the treatment of less
      advanced patients. Issue surrounding long-term adverse effects and genetic
      barriers to raltegravir resistance will be critical in determining the potential
      of this agent.

PMID- 18321240
TI  - Ixabepilone for the treatment of solid tumors: a review of clinical data.
AB  - BACKGROUND: Microtubule stabilizing agents such as taxanes are an integral part
      of therapy for multiple solid tumors. However, due to limitations of these
      agents, newer more effective cytotoxic agents are necessary. Ixabepilone, an
      epothilone B analog, is a novel microtubule stabilizing agent. OBJECTIVE: This
      review provides an updated summary of emerging clinical experience with
      Ixabepilone. METHODS: Phase I, II and III clinical trials presented in abstract
      form or journal articles found within a PubMed search through November 2007 are
      described in this review. RESULTS/CONCLUSION: Ixabepilone offers promising
      clinical activity in a variety of solid tumors. Ixabepilone is FDA-approved for
      the treatment of breast cancer refractory to anthracyclines and taxanes. The
      optimal dose and schedule are still being defined, and the predominant side
      effects are bone marrow suppression and neuropathy.

PMID- 18321241
TI  - Alitretinoin: a comprehensive review.
AB  - BACKGROUND: Alitretinoin (9-cis-retinoic acid) is a unique panagonist retinoid,
      capable of binding to all six known retinoid receptors (RAR-alpha, -beta, -gamma,
      and RXR-alpha, -beta, -gamma). Studies are being carried out to determine how
      best to utilize this characteristic in treatments for conditions such as chronic
      hand dermatitis. OBJECTIVE: To review the literature on alitretinoin. METHODS:
      The scope of the review encompasses ways that alitretinoin is currently and may
      potentially be utilized. RESULTS/CONCLUSIONS: Orally administered alitretinoin is
      a safe and effective treatment for chronic hand dermatitis. Topical treatment
      with alitretinoin can be expanded into other areas such as photoaged skin and
      cutaneous T-cell lymphoma. Despite these benefits, oral alitretinoin will face a
      difficult path attaining approval for use in the US.

PMID- 18321242
TI  - Dihydropteroate synthase from Streptococcus pneumoniae: structure, ligand
      recognition and mechanism of sulfonamide resistance.
AB  - DHPS (dihydropteroate synthase) catalyses an essential step in the biosynthesis
      of folic acid and is the target for the sulfonamide group of antimicrobial drugs.
      In the present paper we report two crystal structures of DHPS from the
      respiratory pathogen Streptococcus pneumoniae: the apoenzyme at 1.8 A (1 A=0.1
      nm) resolution and a complex with DHPP (6-hydroxymethyl-7,8-dihydropterin
      monophosphate) at 2.4 A resolution. The enzyme forms a alpha/beta barrel
      structure, with a highly conserved binding pocket for recognition of the pterin
      substrate, DHPPP (6-hydroxymethyl-7,8-dihydropterin pyrophosphate). There is a
      fixed order of substrate binding: DHPPP binds first, followed by the second
      substrate, pABA (p-aminobenzoic acid). Binding of PP(i) also allows the enzyme to
      recognize pABA or sulfonamide drugs, which act as pABA analogues. Using
      equilibrium and pre-steady state kinetic fluorescence measurements, we show that
      the on-rate for DHPPP binding to the enzyme is relatively low (2.6x10(5) M(-1) x
      s(-1)) and propose that binding of this substrate induces a large scale movement
      of the second loop in the enzyme structure to participate in the formation of the
      pABA-binding site. Two mutations which confer resistance to sulfonamide drugs do
      not affect DHPPP binding, but have a substantial effect on pABA and sulfonamide
      recognition. The results show that binding of DHPPP and pABA are separate
      distinguishable events in the reaction cycle, and that mutations which confer
      resistance to sulfonamide drugs act exclusively on the second step in the binding
      process.

PMID- 18321243
TI  - Monitoring conformational changes during the catalytic cycle of OpuAA, the ATPase
      subunit of the ABC transporter OpuA from Bacillus subtilis.
AB  - The ABC transporter (ATP-binding-cassette transporter) OpuA is one of five
      membrane transport systems in Bacillus subtilis that mediate osmoprotection by
      importing compatible solutes. Just like all bacterial and archaeal ABC
      transporters that catalyse the import of substrates, OpuA (where Opu is
      osmoprotectant uptake) is composed of an ATPase subunit (OpuAA), a transmembrane
      subunit (OpuAB) and an extracellular substrate-binding protein (OpuAC). In
      contrast with many well-known ABC-ATPases, OpuAA is composed not only of a
      catalytic and a helical domain but also of an accessory domain located at its C
      terminus. The paradigm of such an architecture is MalK, the ABC-ATPase of the
      maltose importer of Escherichia coli, for which detailed structural and
      functional information is available. In the present study, we have applied
      solution FRET (Forster resonance energy transfer) techniques using two single
      cysteine mutants to obtain initial structural information on the architecture of
      the OpuAA dimer in solution. Analysing our results in detail and comparing them
      with the existing MalK structures revealed that the catalytic and helical domains
      adopted an arrangement similar to those of MalK, whereas profound differences in
      the three-dimensional orientation of the accessory domain, which contains two CBS
      (cystathionine beta-synthetase) domains, were observed. These results shed new
      light on the role of this accessory domain present in a certain subset of ABC
      ATPase in the fine-tuning of three-dimensional structure and biological function.

PMID- 18321244
TI  - Negative-feedback regulation of FGF signalling by DUSP6/MKP-3 is driven by ERK1/2
      and mediated by Ets factor binding to a conserved site within the DUSP6/MKP-3
      gene promoter.
AB  - DUSP6 (dual-specificity phosphatase 6), also known as MKP-3 [MAPK (mitogen
      activated protein kinase) phosphatase-3] specifically inactivates ERK1/2
      (extracellular-signal-regulated kinase 1/2) in vitro and in vivo. DUSP6/MKP-3 is
      inducible by FGF (fibroblast growth factor) signalling and acts as a negative
      regulator of ERK activity in key and discrete signalling centres that direct
      outgrowth and patterning in early vertebrate embryos. However, the molecular
      mechanism by which FGFs induce DUSP6/MKP-3 expression and hence help to set
      ERK1/2 signalling levels is unknown. In the present study, we demonstrate, using
      pharmacological inhibitors and analysis of the murine DUSP6/MKP-3 gene promoter,
      that the ERK pathway is critical for FGF-induced DUSP6/MKP-3 transcription.
      Furthermore, we show that this response is mediated by a conserved binding site
      for the Ets (E twenty-six) family of transcriptional regulators and that the Ets2
      protein, a known target of ERK signalling, binds to the endogenous DUSP6/MKP-3
      promoter. Finally, the murine DUSP6/MKP-3 promoter coupled to EGFP (enhanced
      green fluorescent protein) recapitulates the specific pattern of endogenous
      DUSP6/MKP-3 mRNA expression in the chicken neural plate, where its activity
      depends on FGFR (FGF receptor) and MAPK signalling and an intact Ets-binding
      site. These findings identify a conserved Ets-factor-dependent mechanism by which
      ERK signalling activates DUSP6/MKP-3 transcription to deliver ERK1/2-specific
      negative-feedback control of FGF signalling.

PMID- 18321245
TI  - Analysis of carboxyl tail function in the skeletal muscle Cl- channel hClC-1.
AB  - Human ClC-1 (skeletal muscle Cl- channel) has a long cytoplasmic C-tail (carboxyl
      tail), containing two CBS (cystathionine beta-synthase) domains, which is very
      important for channel function. We have now investigated its significance
      further, using deletion and alanine-scanning mutagenesis, split channels, GST
      (glutathione transferase)-pull-down and whole-cell patch-clamping. In tagged
      split-channel experiments, we have demonstrated strong binding between an N
      terminal membrane-resident fragment (terminating mid-C-tail at Ser(720) and
      containing CBS1) and its complement (containing CBS2). This interaction is not
      affected by deletion of some sequences, suggested previously to be important,
      particularly in channel gating. Contact between CBS1 and CBS2, however, may make
      a major contribution to assembly of functional channels from such co-expressed
      complements, although the possibility that C-tail fragments could, in addition,
      bind to other parts of the membrane-resident component has not been eliminated.
      We now show such an interaction between a membrane-resident component terminating
      at Ser(720) (but with CBS1 deleted) and a complete C-tail beginning at Leu(598).
      Channel function is rescued in patch-clamped HEK-293T (human embryonic kidney)
      cells co-expressing these same fragments. From our own results and those of
      others, we conclude that the CBS1-CBS2 interaction is not sufficient, in itself,
      for channel assembly, but rather that this might normally assist in bringing some
      part of the CBS2/C-tail region into appropriate proximity with the membrane
      resident portion of the protein. Previously conflicting and anomalous results can
      now be explained by an hypothesis that, for split channels to be functional, at
      least one membrane-resident component must include a plasma membrane trafficking
      signal between Leu(665) and Lys(680).

PMID- 18321246
TI  - Disagreement between subjective and actigraphic measures of sleep duration in a
      population-based study of elderly persons.
AB  - Sleep duration is an important concept in epidemiological studies. It
      characterizes a night's sleep or a person's sleep pattern, and is associated with
      numerous health outcomes. In most large studies, sleep duration is assessed with
      questionnaires or sleep diaries. As an alternative, actigraphy may be used, as it
      objectively measures sleep parameters and is feasible in large studies. However,
      actigraphy and sleep diaries may not measure exactly the same phenomenon. Our
      study aims to determine disagreement between actigraphic and diary estimates of
      sleep duration, and to investigate possible determinants of this disagreement.
      This investigation was embedded in the population-based Rotterdam Study. The
      study population consisted of 969 community-dwelling participants aged 57-97
      years. Participants wore an actigraph and kept a sleep diary for, on average, six
      consecutive nights. Both measures were used to determine total sleep time (TST).
      In 34% of the participants, the estimated TST in the sleep diaries deviated more
      than 1 h from actigraphically measured TST. The level of disagreement between
      diary and actigraphic measures decreased with subjective and actigraphic measures
      of sleep quality, and increased with male gender, poor cognitive function and
      functional disability. Actigraphically measured poor sleep was often accompanied
      by longer subjective estimates of TST, whereas subjectively poor sleepers tended
      to report shorter TST in their diaries than was measured with actigraphy. We
      recommend, whenever possible, to use multiple measures of sleep duration, to
      perform analyses with both, and to examine the consistency of the results over
      assessment methods.

PMID- 18321247
TI  - Increased EEG spectral power density during sleep following short-term sleep
      deprivation in pigeons (Columba livia): evidence for avian sleep homeostasis.
AB  - Birds provide a unique opportunity to evaluate current theories for the function
      of sleep. Like mammalian sleep, avian sleep is composed of two states, slow-wave
      sleep (SWS) and rapid eye-movement (REM) sleep that apparently evolved
      independently in mammals and birds. Despite this resemblance, however, it has
      been unclear whether avian SWS shows a compensatory response to sleep loss (i.e.,
      homeostatic regulation), a fundamental aspect of mammalian sleep potentially
      linked to the function of SWS. Here, we prevented pigeons (Columba livia) from
      taking their normal naps during the last 8 h of the day. Although time spent in
      SWS did not change significantly following short-term sleep deprivation,
      electroencephalogram (EEG) slow-wave activity (SWA; i.e., 0.78-2.34 Hz power
      density) during SWS increased significantly during the first 3 h of the recovery
      night when compared with the undisturbed night, and progressively declined
      thereafter in a manner comparable to that observed in similarly sleep-deprived
      mammals. SWA was also elevated during REM sleep on the recovery night, a response
      that might reflect increased SWS pressure and the concomitant 'spill-over' of SWS
      related EEG activity into short episodes of REM sleep. As in rodents, power
      density during SWS also increased in higher frequencies (9-25 Hz) in response to
      short-term sleep deprivation. Finally, time spent in REM sleep increased
      following sleep deprivation. The mammalian-like increase in EEG spectral power
      density across both low and high frequencies, and the increase in time spent in
      REM sleep following sleep deprivation suggest that some aspects of avian and
      mammalian sleep are regulated in a similar manner.

PMID- 18321248
TI  - Hypertensive encephalopathy presenting with isolated brain stem and cerebellar
      edema.
AB  - Hypertensive encephalopathy typically presents with headache and confusion and
      bilateral parietooccipital vasogenic edema. Brain stem and cerebellar edema in
      hypertensive encephalopathy usually occurs in association with these typical
      supratentorial changes and is usually asymptomatic. We report here an uncommon
      hypertensive patient with isolated, severe, and symptomatic brain stem and
      cerebellar edema with fourth ventricular obstruction and mild hydrocephalus.
      Rapid treatment of hypertension resulted in clinical and radiological
      improvement. Prompt recognition of the cause and aggressive treatment of
      hypertension in such patients are crucial to relieve edema and prevent life
      threatening progression.

PMID- 18321249
TI  - Intravascular ultrasound to assess extracranial vertebral artery restenosis: case
      report.
AB  - We present a case report of a patient who developed restenosis 5 months after
      initial stent placement. computed tomography (CT) angiography revealed a 70%
      stenosis, while conventional angiography revealed a 40% stenosis. An
      intravascular ultrasound (IVUS) was used to assess the degree of narrowing along
      with the mechanism causing the stenosis. IVUS can be utilized to resolve
      discrepancies between imaging modalities for degree of stenosis and also aid in
      determining the mechanism of restenosis after stent placement in the extracranial
      vertebral arteries.

PMID- 18321250
TI  - Neuroimaging findings in hyperargininemia.
AB  - In hyperarginenemia, there is a defect in argininase enzyme, which is a catalyzer
      of urea cycle. Though the pathogenesis of neuronal damage in hyperargininemia is
      not clear, high serum and cerebrospinal fluid arginine levels can be directly
      related with neuronal damage. In this study, our aim was to assess brain magnetic
      resonance images and magnetic resonance spectroscopy (MRS) patterns of two
      siblings with hyperarginenemia. We acquired single voxel MRS from the white
      matter to show the myelination pattern and to figure out any abnormal peak of
      metabolite stored due to enzymatic defect. We observed mild cerebral and
      cerebellar atrophy and infarct at bilateral posterior putamen and insular cortex
      localization on conventional images and elevated choline/creatine ratios and
      abnormal peak at 3.8 ppm, most likely representing arginine deposition. To the
      best of our knowledge, this is the first article revealing the brain MRS pattern
      of hyperargininemia. We reported the clinical and imaging findings of patients
      and discuss the correlation.

PMID- 18321251
TI  - CT angiography is cost-effective for confirmation of internal carotid artery
      occlusions.
AB  - BACKGROUND AND PURPOSE: While sensitive to internal carotid artery (ICA)
      occlusion, carotid ultrasound can produce false-positive results. CT angiography
      (CTA) has a high specificity for ICA occlusion and is safer and cheaper than
      catheter angiography, although less accurate. We determined the cost
      effectiveness of CTA versus catheter angiography for confirming an ICA occlusion
      first suggested by carotid ultrasound. METHODS: A Markov decision-analytic model
      was constructed to estimate the cost-effectiveness of CTA compared with catheter
      angiography in a hypothetical cohort of symptomatic patients with a screening
      examination consistent with an ICA occlusion. Costs in 2004 dollars were
      estimated from Medicare reimbursement. Effectiveness was measured in quality
      adjusted life years. RESULTS: The 2-year cost in the CTA scenario was $9,178, and
      for catheter angiography, $11,531, consistent with a $2,353 cost-savings per
      person for CTA. CTA resulted in accrual of 1.83 quality-adjusted life years while
      catheter angiography resulted in 1.82 quality-adjusted life years. CTA was less
      costly and marginally more effective than catheter angiography. In sensitivity
      analyses, when CTA sensitivity and specificity were allowed to vary across a
      plausible range, CTA remained cost-effective. CONCLUSIONS: After screening
      examination has suggested an ICA occlusion, confirmatory testing with CTA
      provides similar effectiveness to catheter angiography and is less costly.

PMID- 18321252
TI  - To be or not to be a hamlet pair in sympatry.
AB  - Recent adaptive radiations, such as the fringillid finches on the Galapagos
      archipelago or the cichlid fishes in the East African Great Lakes, are invaluable
      model systems for evolutionary and ecological research. Puebla et al., in this
      issue of Molecular Ecology, have established a group of colorful coral reef
      fishes from the Caribbean sea for studying the early phases of species formation
      in a marine adaptive radiation. It appears that local evolutionary processes are
      important in this system, which might have even triggered in situ speciation.

PMID- 18321253
TI  - Population genetic analyses of Hypoplectrus coral reef fishes provide evidence
      that local processes are operating during the early stages of marine adaptive
      radiations.
AB  - Large-scale, spatially explicit models of adaptive radiation suggest that the
      spatial genetic structure within a species sampled early in the evolutionary
      history of an adaptive radiation might be higher than the genetic differentiation
      between different species formed during the same radiation over all locations.
      Here we test this hypothesis with a spatial population genetic analysis of
      Hypoplectrus coral reef fishes (Serranidae), one of the few potential cases of a
      recent adaptive radiation documented in the marine realm. Microsatellite analyses
      of Hypoplectrus puella (barred hamlet) and Hypoplectrus nigricans (black hamlet)
      from Belize, Panama and Barbados validate the population genetic predictions at
      the regional scale for H. nigricans despite the potential for high levels of gene
      flow between populations resulting from the 3-week planktonic larval phase of
      Hypoplectrus. The results are different for H. puella, which is characterized by
      significantly lower levels of spatial genetic structure than H. nigricans. An
      extensive field survey of Hypoplectrus population densities complemented by
      individual-based simulations shows that the higher abundance and more continuous
      distribution of H. puella could account for the reduced spatial genetic structure
      within this species. The genetic and demographic data are also consistent with
      the hypothesis that H. puella might represent the ancestral form of the
      Hypoplectrus radiation, and that H. nigricans might have evolved repeatedly from
      H. puella through ecological speciation. Altogether, spatial genetic analysis
      within and between Hypoplectrus species indicate that local processes can operate
      at a regional scale within recent marine adaptive radiations.

PMID- 18321254
TI  - Estimating contemporary early life-history dispersal in an estuarine fish:
      integrating molecular and otolith elemental approaches.
AB  - Dispersal during the early life history of the anadromous rainbow smelt, Osmerus
      mordax, was examined using assignment testing and mixture analysis of multilocus
      genotypes and otolith elemental composition. Six spawning areas and associated
      estuarine nurseries were sampled throughout southeastern Newfoundland. Samples of
      adults and juveniles isolated by > 25 km displayed moderate genetic
      differentiation (F(ST) ~ 0.05), whereas nearby (< 25 km) spawning and nursery
      samples displayed low differentiation (F(ST) < 0.01). Self-assignment and mixture
      analysis of adult spawning samples supported the hypothesis of independence of
      isolated spawning locations (> 80% self-assignment) with nearby runs self
      assigning at rates between 50 % and 70%. Assignment and mixture analysis of
      juveniles using adult baselines indicated high local recruitment at several
      locations (70-90%). Nearby (< 25 km) estuaries at the head of St Mary's Bay
      showed mixtures of individuals (i.e. 20-40% assignment to adjacent spawning
      location). Laser ablation inductively coupled mass spectrometry transects across
      otoliths of spawning adults of unknown dispersal history were used to estimate
      dispersal among estuaries across the first year of life. Single-element trends
      and multivariate discriminant function analysis (Sr:Ca and Ba:Ca) classified the
      majority of samples as estuarine suggesting limited movement between estuaries (<
      0.5%). The mixtures of juveniles evident in the genetic data at nearby sites and
      a lack of evidence of straying in the otolith data support a hypothesis of
      selective mortality of immigrants. If indeed selective mortality of immigrants
      reduces the survivorship of dispersers, estimates of dispersal in marine
      environments that neglect survival may significantly overestimate gene flow.

PMID- 18321255
TI  - A population genomic analysis of species boundaries: neutral processes, adaptive
      divergence and introgression between two hybridizing plant species.
AB  - Little is known about the nature of species boundaries between closely related
      plant species and about the extent of introgression as a consequence of
      hybridization upon secondary contact. To address these topics we analyzed genome
      wide differentiation between two closely related Silene species, Silene latifolia
      and S. dioica, and assessed the strength of introgression in sympatry. More than
      300 AFLP markers were genotyped in three allopatric and three sympatric
      populations of each species. Outlier analyses were performed separately for
      sympatric and allopatric populations. Both positive and negative outlier loci
      were found, indicating that divergent and balancing selection, respectively, have
      shaped patterns of divergence between the two species. Sympatric populations of
      the two species were found to be less differentiated genetically than allopatric
      populations, indicating that hybridization has led to gene introgression. We
      conclude that differentiation between S. latifolia and S. dioica has been shaped
      by a combination of introgression and selection. These results challenge the view
      that species differentiation is a genome-wide phenomenon, and instead support the
      idea that genomes can be porous and that species differentiation has a genic
      basis.

PMID- 18321256
TI  - Heat shock protein 101 effects in A. thaliana: genetic variation, fitness and
      pleiotropy in controlled temperature conditions.
AB  - The Hsp100/ClpB heat shock protein family is ancient and required for high
      temperature survival, but natural variation in expression and its phenotypic
      effects is unexplored in plants. In controlled environment experiments, we
      examined the effects of variation in the Arabidopsis cytosolic AtHsp101
      (hereafter Hsp101). Ten wild-collected ecotypes differed in Hsp101 expression
      responses across a 22 to 40 degrees C gradient. Genotypes from low latitudes
      expressed the least Hsp101. We tested fitness and pleiotropic consequences of
      varying Hsp101 expression in 'control' vs. mild thermal stress treatments (15/25
      degrees C D/N vs. 15/25 degrees D/N plus 3 h at 35 degrees C 3 days/week).
      Comparing wild type and null mutants, wt Columbia (Col) produced approximately
      33% more fruits compared to its Hsp101 homozygous null mutant. There was no
      difference between Landsberg erecta null mutant NIL (Ler) and wt Ler; wt Ler
      showed very low Hsp101 expression. In an assay of six genotypes, fecundity was a
      saturating function of Hsp101 content, in both experimental treatments. Thus, in
      addition to its essential role in acquired thermal tolerance, Hsp101 provides a
      substantial fitness benefit under normal growth conditions. Knocking out Hsp101
      decreased fruit production, days to germination and days to bolting, total dry
      mass, and number of inflorescences; it increased transpiration rate and
      allocation to root mass. Root : total mass ratio decayed exponentially with
      Hsp101 content. This study shows that Hsp101 expression is evolvable in natural
      populations. Our results further suggest that Hsp101 is primarily an emergency
      high-temperature tolerance mechanism, since expression levels are lower in low
      latitude populations from warmer climates. Hsp101 expression appears to carry an
      important trade-off in reduced root growth. This trade-off may select for
      suppressed expression under chronically high temperatures.

PMID- 18321258
TI  - National survey on edentulism and its geographic distribution, among Mexicans 18
      years of age and older (with emphasis in WHO age groups).
AB  - To determine the prevalence of edentulism in adults aged 18 years and older in
      Mexico and to describe its distribution in 20 of the 32 States in Mexico,
      highlighting the experience in the WHO age groups. A secondary analysis of the
      National Performance Evaluation Survey 2002-2003 (representative at the state
      level and part of the Word Health Survey) was undertaken. The sample design was
      probabilistic, stratified and through conglomerates. Data on dental conditions
      were available only for 20 of the 32 states of Mexico, leading to a total of 24
      159 households (N = 54 638 654). The percentage of edentulism was determined as
      the proportion of subjects that self-reported complete loss of teeth. Data were
      analyzed using the SVY module for complex surveys in STATA 8.2. The mean age was
      41.3 +/- 17.0 years (range 18-99). An estimated 6.3% (N = 3 437 816) of the
      population > or =18 years was edentulous. Lowest prevalences were observed in the
      states of Tlaxcala, Puebla and the Estado de Mexico with 3.4%, 3.8% and 4.5%,
      respectively. Highest prevalences were observed in San Luis Potosi, Colima, and
      Michoacan with 10.3%, 10.2% and 10.1%, respectively. Following the WHO age
      groups, the prevalence ranged from 2.4% in the 35-44 group through 25.5% in the
      65-74 group. No obvious association between socio-economic and socio-demographic
      indicators at the state level and prevalence of edentulism was found. The
      prevalence of complete tooth loss observed in the present study varied greatly
      across states, although no straightforward association was found with socio
      economic and socio-demographic indicators at the state level. This study could
      serve as a baseline to enable future evaluations of the oral status of Mexican
      adults and elders, following WHO age groups.

PMID- 18321259
TI  - Tooth loss and prosthodontic rehabilitation among 35- to 44-year-old Iranians.
AB  - This study aimed to investigate the frequency of tooth loss and the magnitude of
      prosthodontic rehabilitation based on socio-demographic information among 35- to
      44-year-old Iranians. Data (n = 8240) were collected by 33 examiners as part of a
      national survey using WHO criteria for sampling and clinical diagnosis. Gender,
      age, place of residence and level of education served as socio-demographic
      information. The number of teeth, functional dentition (subjects with 20 or more
      teeth) and prosthodontic rehabilitation were used as clinical variables. The chi
      square test and logistic regression analysis were the methods of statistical
      evaluation. Of all subjects, 3% were edentulous. Of dentate subjects, 3% had 1-9
      teeth, 21% had 10-19 teeth, 37% had 20-24 teeth and 39% had 25-28 teeth. In
      total, 76% of dentate subjects enjoyed a functional dentition. Among dentate
      subjects, 11% of the men and 16% of the women had prosthodontic rehabilitation
      with higher figures (P < 0.001) among women, older subjects and urban residents.
      Having a functional dentition was more likely among those with higher levels of
      education [odds ratios (OR) = 1.8, 95% confidence intervals (CI) = 1.6-2.1].
      Women (OR = 2.4, 95% CI = 1.8-3.0) and urban residents (OR = 2.4, 95% CI = 1.8
      3.3) were the most likely groups to have prosthodontic rehabilitation. Having
      prosthodontic rehabilitation was more likely among those lacking a functional
      dentition (OR = 6.0, 95% CI = 4.8-7.6). The greatest unmet treatment needs were
      found among those without a functional dentition. Functional dentition should be
      set as a primary oral health goal among working-age adults.

PMID- 18321260
TI  - Removable prosthodontic services, including implant-supported overdentures,
      provided by dentists and denturists.
AB  - The aim of this study was to evaluate the provision of removable prosthodontic
      services, including implant-supported overdentures, by dentists and denturists. A
      structured questionnaire was mailed to 474 randomly chosen dentists and 156
      denturists registered to practise in New Zealand. Information was sought on the
      range of removable prosthodontic services provided (including implant-supported
      overdentures) and the professional fees charged for them. From 410 respondents,
      there was an overall response rate of 67.43%; 290 came from the dentists (males
      78.6%, n = 228; females 21.48%, n = 62) and 120 from denturists (males 91.7%, n =
      110; females 8.3%, n = 10). Most respondents were over 40 years of age, with one
      in three denturists (but only one in seven dentists) over 60 years of age. The
      extent of removable prosthodontic services varied. One-third of dentists referred
      complete denture patients and denturists referred a similar number of immediate
      denture cases. Denturists' complete denture, immediate denture and single reline
      prices were generally lower than those from dentists. Removable partial denture
      prices were similar. Implant-supported overdentures were recommended for
      edentulous patients by one-third of the dentists and three out of four
      denturists. Forty per cent of denturists (but only 10% of dentists) charged
      <NZ$1000 for complete dentures. (1NZ$ = US$ 0.75; 1NZ$ = euro 0.56; 1NZ$ = GBP
      0.38) Implant-supported overdenture fees were predominantly in the range of
      NZ$1500-3000 for both groups, but one in four dentists and one in six denturists
      charged more than NZ$3000. Although both denturists and dentists both provide
      prosthodontic services, there is a professional fee differential between them.
      Denturists' lower fees provide a more economic option. Denturists are likely to
      steadily develop further inroads into the implant-supported overdenture market.

PMID- 18321261
TI  - Factors affecting dental anxiety and beliefs in an Indian population.
AB  - The purpose of this study was to describe the possible factors that may affect
      dental anxiety and beliefs and to validate and test the psychometric properties
      of the Modified Dental Anxiety Scale (MDAS) and a Modified Dental Beliefs Scale
      (MDBS) among the patients attending a university dental clinic in India. A cross
      sectional study design was used. A total of 482 general dental patients attending
      a university dental clinic returned completed forms of the Indian translations of
      the MDAS and MDBS. General information about the age, sex, occupation and
      educational qualifications of the respondents as well as information about past
      dental experiences was also collected. All the statistical analysis was carried
      out by the spss (version 10) statistical software package. The Indian
      translations of the MDAS and the MDBS were found to be internally reliable with a
      Cronbach's alpha of 0.78 and 0.85, respectively. Validity was demonstrated by a
      statistically significant correlation between the MDAS and the MDBS scores with
      the correlation coefficient of 0.47. Age was also inversely related to dental
      anxiety. Anxiety scores were higher among the less educated patients. Those who
      had a prior unpleasant dental experience showed higher dental anxiety and more
      negative dental beliefs. The data obtained in this study provided strong evidence
      for the psychometric properties of the Indian version of the MDAS and the MDBS.

PMID- 18321262
TI  - Effect of pre-processing surface treatments of acrylic teeth on bonding to the
      denture base.
AB  - The aim of this study was to examine the bond strength between acrylic teeth
      after various surface treatments and processing with either a heat- or microwave
      polymerized denture base material. Specimens were prepared and tested according
      to the methods described in American National Standard/American Dental
      Association Specification No.15 (Synthetic Polymer Teeth) using a special
      assembly. Three brands of acrylic teeth were used with the following treatments:
      control (no treatment), grinding and grinding plus sandblasting. Treatment groups
      were further divided into two denture base processing subgroups: heat-polymerized
      and microwave-polymerized methods. Denture base processing to the acrylic teeth
      was performed according to the manufacturer's recommendations. Bond strength test
      was performed using a universal testing machine with five specimens and each
      specimen is composed of six anterior teeth per experimental group. Data were
      analysed using a three-way anova and the Scheffe'F-test post hoc pair wise
      comparison at the 95% significance level. The mean bond strength values ranged
      from 33.1 +/- 4.1 to 51.6 +/- 2.5 MPa. The bond strength values of sandblasted
      surfaces were significantly higher than those of the ground surface and the
      control (P < 0.05). Combined (acrylic tooth and denture base resin) cohesive
      failures were disclosed in all tested samples. Acrylic tooth surface pre
      processed surface treatment with grinding plus sandblasting and processed with a
      heat-polymerized denture base provided the greatest bond strength between acrylic
      tooth and denture base.

PMID- 18321263
TI  - The effect of hydrogen peroxide concentration on metal ion release from dental
      casting alloys.
AB  - There are concerns that tooth bleaching agents may adversely affect dental
      materials. The aim of this study was to test the hypothesis that increasing
      concentrations of hydrogen peroxide (HP) are more effective than water at
      increasing metal ion release from two typical dental casting alloys during
      bleaching. Discs (n = 28 for each alloy) were prepared by casting and heat
      treated to simulate a typical porcelain-firing cycle. Discs (n = 7) of each alloy
      were immersed in either 0%, 3%, 10% or 30% (w/v) HP solutions for 24 h at 37
      degrees C. Samples were taken for metal ion release determination using
      inductively coupled plasma-mass spectrometry and the data analysed using a two
      way anova followed by a one-way anova. The surface roughness of each disc was
      measured using a Talysurf contact profilometer before and after bleaching and the
      data analysed using a paired t-test. With the exception of gold, the differences
      in metal ion concentration after treatment with 0% (control) and each of 3%, 10%
      and 30% HP (w/v) were statistically significant (P < 0.05). Metal ion release
      from the two alloys increased with increasing HP concentrations (over 3000%
      increase in Ni and 1400% increase in Pd ions were recorded when HP concentration
      increased from 0% to 30%). Surface roughness values of the samples before and
      after bleaching were not significantly different (P > 0.05) Exposure of the two
      dental casting alloys to HP solutions increased metal ion release of all the
      elements except gold.

PMID- 18321264
TI  - Effects of implant surface roughness and stiffness of grafted bone on an
      immediately loaded maxillary implant: a 3D numerical analysis.
AB  - This study investigated the effects of the stiffness of a maxillary sinus graft
      and the surface roughness of an immediately loaded implant using a non-linear
      three-dimensional finite element (FE) analysis (3D). Six FE models were created,
      including two stiffness values of grafted bone (345 and 3450 MPa of elastic
      modulus) and three conditions of implant-bone interfaces (Frictional coefficient
      of 0.3 for machined surface, 0.45 for rough implant surface and a bonded implant
      bone interface for an osseointegrated implant). Computer tomographic images of a
      human skull were used to construct a posterior maxillary model. All implants were
      designed via the computer aided design software with a spiral threaded
      configuration. Three loading scenarios were investigated for each of the six
      models; axial loading and lateral loadings at 30 degrees and 60 degrees . The
      results showed that a 60 degrees lateral loading has scored the highest level of
      bone stresses among the three loading conditions. Immediately loaded implants
      with 0.3 frictional coefficient have suffered the highest bone stresses which
      were higher than those with bonded interface by about 57%. Increasing the
      frictional coeffecient to 0.45, however, did not show any benefits in reducing
      the peak bone stress. Raising the stiffness of grafted bone diminished the bone
      stress by about 10% in both the immediately loaded and the osseointegrated
      implants. It was also noted that increasing graft stiffness and implant surface
      roughness reduced the sliding at the implant-bone interface which may improve the
      implant stability and long-term survival.

PMID- 18321265
TI  - Accuracy and stability of impression materials subjected to chemical disinfection
      - a literature review.
AB  - Disinfection of impressions by immersion or spraying with disinfecting solutions
      is considered nowadays mandatory for effective infection control. The purpose of
      this review was to examine existing evidence on the effects that chemical
      disinfection may have on critical qualities of impressions, namely dimensional
      accuracy and stability over time. A PubMed search was conducted to include
      original laboratory research articles written in English, published between 1980
      and 2005 in peer-reviewed journals and investigating the effect of chemical
      disinfection, by immersion or spraying, on the dimensional changes that the
      impression materials experience after setting. Studies were also sought manually,
      by tracing the references cited in the retrieved articles. The reports on
      dimensional changes of disinfected impression materials, although rather
      numerous, are difficult to compare and analyze because of variations of the
      experimental design. The investigations broadly agree that the disinfection
      process does not generally affect the dimensional integrity of the impressions,
      in spite of the statistically significant differences occasionally found.
      However, the immersion in the disinfecting solution encourages water absorption
      phenomena in the case of the so-called hydrophilic impression materials,
      especially after the long-term immersion. Chemical interactions between
      impressions and disinfectants may occur, but they do not appear to influence the
      dimensional behaviour of the former. The overall effect of the disinfection is
      influenced not only by the changes experienced by the impression per se, but also
      by the alterations of the acrylic tray containing the impression and of the
      gypsum product poured in it.

PMID- 18321266
TI  - Discovering new treatments for sensitive teeth: the long path from biology to
      therapy.
AB  - Tooth sensitivity is a common dental pain condition where sufferers experience
      brief episodes of sharp well-localized pain when their teeth are subjected
      innocuous stimuli such as cold, air-currents and probing with a metallic
      instrument. In this review, we will make no attempt to describe all the
      treatments that have been developed to treat tooth sensitivity. We will review
      the basic anatomic and physiological mechanisms responsible for sensitivity. The
      insights into the dental lesions responsible for tooth sensitivity, as well as
      the physiological processes linking stimuli and pain generation have suggested
      several treatments and preventive strategies. Unfortunately, many tooth
      sensitivity treatments fail to perform better than placebos in clinical trials
      that seek to assess the effect of agents on pain symptoms. In the case of the
      most commonly used self-applied desensitizing agent, potassium salts, the
      mechanism of action established by laboratory and animal models may not apply to
      clinical use. Thus results obtained with laboratory and animal models must be
      applied with care to clinical use. Clinical literature suggests that tooth
      sensitivity is the symptomatic manifestation of significant dental problems, such
      as wear and other forms of non-carious tooth structure loss. These conditions are
      increasing in frequency as people age, retaining their natural teeth longer. They
      are frequently the consequences of aggressive oral hygiene practices and diets
      rich in acids. Treatments directed at the underlying causes rather than the
      symptoms of tooth sensitivity would hinder the development of these lesions and
      provide researchers with objective targets for assessing therapeutic efficacy.

PMID- 18321267
TI  - Editorial: Professors as leaders.

PMID- 18321268
TI  - A review of the psychosocial issues for nurses in male genitalia-related care.
AB  - AIM: This literature review aimed to highlight psychosocial issues for nurses in
      the practice of male genitalia-related care so as to guide the improvement of the
      teaching and practice of male genitalia-related care. BACKGROUND: Male genitalia
      related care is common in hospitals and in the community. In several conditions,
      e.g. incontinence, postradiotherapy or following operation for cancer of
      genitalia, bladder, colon or rectum, patients will require male genitalia-related
      care. Patients who require male genitalia-related care may encounter psychosocial
      and/or sexual dysfunction. In the holistic approach to men's health, nurses are
      expected to meet patients' psychosocial and sexual needs, while the literature
      suggests that nurses' perceptions and attitudes in providing certain male
      genitalia-related care, e.g. genital hygiene, sexual counselling, are negative.
      METHOD: Systematic literature review. CONCLUSION: Issues surrounding male
      genitalia-related care for nurses are complicated and may be related to privacy,
      intimacy, sexuality, dirty work and emotional discomfort. Age, gender, race and
      social class could compound these issues. Relevance to clinical practice. Nurses'
      negative perceptions, responses and attitudes towards male genitalia-related care
      may exacerbate patients' conditions under which male genitalia-related care is
      required. Appropriate strategies should be developed to overcome these problems.

PMID- 18321269
TI  - Workforce profile, organisation structure and role responsibility for ventilation
      and weaning practices in Australia and New Zealand intensive care units.
AB  - AIMS AND OBJECTIVES: To provide an analysis of the scope of nursing practice and
      inter-professional role responsibility for ventilatory decision-making in
      Australian and New Zealand (ANZ) intensive care units (ICU). BACKGROUND:
      Currently, little empirical data describe nurses' role in decision-making for
      ventilation and its weaning. Delineation of roles and responsibilities for
      ventilatory practices vary according to unit structure, staffing and skill-mix,
      patient case-mix and unit leadership models. METHODS: Self-administered
      questionnaire sent to nurse managers of eligible ICUs within ANZ. Results. Survey
      responses were available from 54/180 ICUs. The majority (71%) of responding ICUs
      were located within metropolitan areas and categorised as a tertiary level ICU
      (50%). The mean number of nurses employed per ICU bed was 4.7 in Australia and
      4.2 in NZ, with 69% (IQR: 47-80%) of nurses holding a postgraduate specialty
      qualification. All units reported a 1:1 nurse-to-patient ratio for ventilated
      patients with 71% reporting a 1:2 nurse-to-patient ratio for non- ventilated
      patients. Key ventilator decisions, including assessment of weaning and
      extubation readiness, were reported as predominantly made by nurses and doctors
      in collaboration. Overall, nurses described high levels of autonomy and influence
      in ventilator decision-making. Decisions to change ventilator settings, including
      FiO(2) (91%, 95% CI: 80-97), ventilator rate (65%, 95% CI: 51-77) and pressure
      support adjustment (57%, 95% CI: 43-71), were made independently by nurses.
      CONCLUSIONS: The results of this survey suggest, within the ANZ context, nurses
      participate actively in ventilation and weaning decisions. In addition, the
      results support an association between the education profile and skill-mix of
      nurses and the level of collaborative practice in ICU. Relevance to clinical
      practice. Mechanical ventilation may result in significant complications if not
      applied appropriately. Collaborative practice that encourages nursing input into
      decision-making may improve patient outcomes and reduce complications.

PMID- 18321270
TI  - Evaluating outcomes of the emergency nurse practitioner role in a major urban
      emergency department, Melbourne, Australia.
AB  - AIMS AND OBJECTIVES: The aim of this study was to evaluate the impact of the
      introduction of Emergency Nurse Practitioner Candidates (ENPC) on waiting times
      and length of stay of patients presenting to a major urban Emergency Department
      (ED) in Melbourne, Australia. BACKGROUND: As part of a Victorian state funded
      initiative to improve patient outcomes, the role of the Emergency Nurse
      Practitioner has been developed. The integration and implementation of this role,
      is not only new to the Alfred Emergency and Trauma Centre but to EDs in
      Melbourne, Australia, with aims of providing holistic and comprehensive care for
      patients. DESIGN: A retrospective case series of all patients with common ED
      diagnostic subgroups were included. The ENPC group (n = 572) included all
      patients managed by the ENPC and the Traditional Model (TM) group (n = 2584)
      included all patients managed by the traditional medical ED model of care.
      Outcome measures included waiting times and length of stay. RESULTS:
      Statistically significant differences were evident between the two groups in
      waiting times and length of stay in the ED. The overall median waiting time for
      emergency patients to be seen by the ENPC was less than for the TM group [median
      (IQR): ENPC 12 (5.5-28) minutes; TM 31 (11.5-76) minutes (Wilcoxon p < 0.001)].
      Length of stay in the ED was also significantly reduced in the ENPC group [median
      (IQR): ENPC 94 (53.5-163.5) minutes; TM 170 (100-274) minutes (Wilcoxon p <
      0.001)]. The comparison of overall waiting times for ENPC shifts vs. non-ENPC
      shifts revealed significant differences [median (IQR): ENPC rostered 24 (9-52)
      minutes; ENPC not rostered 33 (13-80.5) minutes (Wilcoxon p < 0.001)].
      CONCLUSIONS: This study has demonstrated that ENPCs implementation in Melbourne,
      Australia were associated with significantly reduced waiting times and length of
      stay for emergency patients. Emergency Nurse Practitioners should be considered
      as a potential long term strategy to manage increased service demands on EDs.
      Relevance to clinical practice. This study is the first in Australia with a
      significant sample size to vigorously compare ENPC waiting times and length of
      stay outcomes with the TM model of care in the ED. The study suggests that ENPCs
      can have a favourable impact on patient outcomes with regard to waiting times and
      length of stay.

PMID- 18321271
TI  - The meaning of consolation as experienced by nurses in a home-care setting.
AB  - AIMS AND OBJECTIVE: The aim of this study was to illuminate nurses' experiences
      of consolation and how these experiences relate to suffering and care.
      BACKGROUND: Consolation is commonly associated with the relief of suffering. The
      question of consolation in terms of its definition and relevance for care has,
      however, been a matter of discussion among nurse researchers. The question raised
      concerns about the nature of consolation, its place and its role in relation to
      care and the caring sciences. DESIGN: An explorative qualitative interview study
      with 12 participants, six registered and six enrolled nurses, was carried out in
      a home-care context. METHODS: A phenomenological-hermeneutic method inspired by
      the French philosopher Paul Ricoeur was used for the text analysis. Results. Two
      main aspects of consolation appeared: 'the present consolation', which is
      flexible, sustaining and opening and 'the absent consolation', which conceals the
      suffering and is incapable of consoling. The result was interpreted from a
      philosophical-ethical perspective, based on the works of Levinas and Logstrup.
      CONCLUSIONS: Consolation appears as a complex phenomenon, both in terms of its
      existence and its absence consolation, constituting a caring and non-caring
      consolation. A caring consolation entails meeting the other as different and
      being present in a way that gives the other space to be the one he or she really
      is. It requires acceptance, accepting the sufferer and his/her way of suffering
      as unique. Relevance to clinical practice. The clinical nurse is involved in
      complex care situations, which entails both reflecting upon and using intuition
      when consoling. A caring consolation is a contradictory phenomenon that requires
      a nurse to be capable of both reflecting upon and acting intuitively on the
      unique suffering of the other.

PMID- 18321272
TI  - From critical care to comfort care: the sustaining value of humour.
AB  - AIMS AND OBJECTIVES: To identify commonalities in the findings of two research
      studies on humour in diverse settings to illustrate the value of humour in team
      work and patient care, despite differing contexts. Background. Humour research in
      health care commonly identifies the value of humour for enabling communication,
      fostering relationships, easing tension and managing emotions. Other studies
      identify situations involving serious discussion, life-threatening circumstances
      and high anxiety as places where humour may not be appropriate. Our research
      demonstrates that humour is significant even where such circumstances are common
      place. METHOD: Clinical ethnography was the method for both studies. Each
      researcher conducted observational fieldwork in the cultural context of a
      healthcare setting, writing extensive fieldnotes after each period of
      observation. Additional data sources were informal conversations with patients
      and families and semi-structured interviews with members of the healthcare team.
      Data analysis involved line-by-line analysis of transcripts and fieldnotes with
      identification of codes and eventual collapse into categories and overarching
      themes. RESULTS: Common themes from both studies included the value of humour for
      team work, emotion management and maintaining human connections. Humour served to
      enable co-operation, relieve tensions, develop emotional flexibility and to
      'humanise' the healthcare experience for both caregivers and recipients of care.
      CONCLUSIONS: Humour is often considered trivial or unprofessional; this research
      verifies that it is neither. The value of humour resides, not in its capacity to
      alter physical reality, but in its capacity for affective or psychological change
      which enhances the humanity of an experience, for both care providers and
      recipients of care. Relevance to clinical practice. In the present era which
      emphasises technology, efficiency and outcomes, humour is crucial for promoting
      team relationships and for maintaining the human dimension of health care. Nurses
      should not be reluctant to use humour as a part of compassionate and personalised
      care, even in critical situations.

PMID- 18321273
TI  - The challenges of caring in a technological environment: critical care nurses'
      experiences.
AB  - PURPOSE: This paper presents and discusses the findings from a phenomenological
      study which illuminated the lived experiences of experienced critical care nurses
      caring within a technological environment. BACKGROUND: While nursing practice is
      interwoven with technology, much of the literature in this area is speculative.
      Moreover, there is a debate as to whether and how 'high tech' and 'high touch'
      are reconcilable; this orientation is referred to as the optimism vs. pessimism
      debate. On a personal level, the motivation for this study came from the author's
      13 years' experience in the critical care area. METHOD: Following ethical
      approval, 10 experienced nurses from two cardiothoracic critical care units in
      Ireland participated in the study. A Heideggerian phenomenological methodology
      was used. Data collection consisted of unstructured interviews. A method of data
      analysis described by Walters was used. FINDINGS: The findings provide research
      based evidence to illuminate further the optimistic/pessimistic debate on
      technology in nursing. While the study demonstrates that the debate is far from
      resolved, it reveals a new finding: life-saving technology that supports the
      lives of critically ill patients can bring experienced nurses very close to their
      patients/families. The three main themes that emerged: 'alien environment',
      'pulling together' and 'sharing the journey' were linked by a common thread of
      caring. CONCLUSION: Experienced critical care nurses are able to transcend the
      obtrusive nature of technology to deliver expert caring to their patients.
      However, the journey to proficiency in technology is very demanding and novice
      nurses have difficulty in caring with technology. Relevance to clinical practice.
      It is recommended that more emphasis be placed on supporting, assisting and
      educating inexperienced nurses in the critical care area and that the use of
      technology in nursing be given serious consideration.

PMID- 18321274
TI  - Commentary on Kristofferzon M-L, Lofmark R & Carlsson M (2007) Striving for
      balance in daily life: experiences of Swedish women and men shortly after a
      myocardial infarction. Journal of Clinical Nursing 16, 391-401.

PMID- 18321276
TI  - Commentary on McGowan B (2006) 'Who do they think they are? Undergraduate
      perceptions of the definition of supernumerary status and how it works in
      practice'. Journal of Clinical Nursing 15, 1099-1105.

PMID- 18321277
TI  - Commentary on Xia C & McCutcheon H (2006) Mealtimes in hospital--who does what?
      Journal of Clinical Nursing 15, 1221-1227.

PMID- 18321278
TI  - Commentary on Prowse M (2007) Postoperative pain in older people: a review of the
      literature. Journal of Clinical Nursing 16, 84-97.

PMID- 18321280
TI  - Commentary on Hegney D (2006) Workforce issues in nursing in Queensland: 2001 and
      2004. Journal of Clinical Nursing 15, 1521-1530.

PMID- 18321282
TI  - Commentary on Norris T & Melby V (2006) The acute care nurse practitioner:
      challenging existing boundaries of emergency nurses in the United Kingdom.
      Journal of Clinical Nursing 15, 253-263.

PMID- 18321284
TI  - Editorial: Dyspnoea and pain: an interesting analogy.

PMID- 18321285
TI  - A review of outcomes of individualised nursing interventions on adult patients.
AB  - AIMS AND OBJECTIVES: This review describes the outcomes of individualised nursing
      interventions on adult patients. Background. Although the delivery of
      individualised nursing interventions is important there is limited evidence about
      how these interventions enhance patient outcomes. METHODS: A computerised search
      was undertaken using the Cochrane Library, MEDLINE, CINAHL and PsycINFO. The
      selection criteria chosen were: reports of individualised nursing interventions
      focusing on adult patients in a variety of health care settings and using
      experimental designs. These involved randomised controlled trials, clinical
      controlled trials and pre- and posttest controlled studies. After a four-stage
      inclusion strategy 31 documents were accepted for the review. RESULTS: The
      studies were mostly focused in preventative arenas such as health promotion and
      counselling. Others were care of older people in the community and in hospital
      and patients with chronic diseases. Over half of the nursing interventions (58%)
      involved educational or counselling activities which seem to be more effective
      than ordinary, standardised or routine education and counselling. Overall, 81% of
      the studies reported a positive impact of individualised interventions on patient
      outcomes showing that there is evidence, though limited, that individualised
      interventions can produce positive patient outcomes. CONCLUSIONS: There is
      sufficient evidence, especially in specific areas such as patient education and
      counselling, to acknowledge that individualised interventions are superior to non
      individualised interventions. Evidence for this effect within clinical nursing
      interventions on patient outcomes was limited by the scarcity of research in this
      area. There is a need for additional intervention studies to determine the effect
      of individualised interventions in a wide variety of contexts. Relevance to
      clinical practice. Experience of health is individual. Therefore, nursing
      interventions should also be individualised to each patient. These findings show
      some promise that individualised interventions may be useful in delivering
      positive patient outcomes.

PMID- 18321286
TI  - Fatigue experience and coping strategies in Taiwanese lung cancer patients
      receiving chemotherapy.
AB  - AIMS: The aim of this cross-sectional study was to explore fatigue levels and
      fatigue-coping strategies in Taiwanese lung cancer patients receiving
      chemotherapy. BACKGROUND: Lung cancer is now recognized as one of the most common
      cancers in Taiwan, with a high prevalence of mortality. As chemotherapy
      progresses, fatigue is a common cause of symptom distress. METHODS: Data on
      demographic and disease-related characteristics were gathered from the medical
      record, and data on fatigue and coping strategies were gathered by questionnaires
      administered to 101 lung cancer patients receiving chemotherapy. RESULTS: The
      mean fatigue score for the total sample was 8.0 (SD = 5.0, range = 0-20),
      indicating light-to-moderate fatigue. The majority of patients (n = 76, 75.2%)
      had a baseline haemoglobin level of <or=12 g/dl and a significantly greater (t =
      2.7, p < 0.01) mean fatigue score (8.5 SD 4.6) than patients with haemoglobin >12
      g/dl (6.2 SD 5.7). Fatigue levels were significantly higher in patients receiving
      a third course of chemotherapy than in those receiving a first course (F = 3.7, p
      = 0.03). The most commonly used management category was energy conservation (n =
      659), and the most commonly used strategy was sitting (n = 101) and lying down (n
      = 98). However, participants rated exercise (mean = 3.9), sleep (mean = 3.8) and
      walking (mean = 3.6) as the most effective. CONCLUSION: This study highlighted
      the management of fatigue problems in lung cancer patients receiving
      chemotherapy, especially in respecting patients' self-report of fatigue
      management strategies. Relevance to clinical practice. Health care providers
      should carefully assess patients for fatigue while they are receiving
      chemotherapy. These patients and their caregivers should be taught to notice
      fatigue and encouraged to choose coping strategies that reduce fatigue level,
      thus improving their quality of life.

PMID- 18321287
TI  - Evaluating screening performances of the Fagerstrom tolerance questionnaire, the
      Fagerstrom test for nicotine dependence and the heavy smoking index among
      Taiwanese male smokers.
AB  - AIM: To compare screening performances of the Fagerstrom Tolerance Questionnaire
      (FTQ), the Fagerstrom test for nicotine dependence (FTND) and the Heavy Smoking
      Index (HSI) with a view to determining the optimum cutoff scores using biomarkers
      as standards. BACKGROUND: Previous studies proposed inconsistent cutoff scores
      for the FTQ, the FTND as signalling nicotine dependence and these scores were
      established by applying diverse standards. METHOD: Receiver operating
      characteristic (ROC) analyses were used in pursuit of the study's objectives. Two
      hundred and forty-five male smokers were recruited in 2005 from among those
      attending public health stations in southern Taiwan. The three self-report
      measures of nicotine dependence were compared with the saliva cotinine and
      expired carbon monoxide (CO). The expired CO level was tested by means of a Micro
      Smokerlyzer, while salivary cotinine was analysed using an enzyme-linked
      immunosorbent assay. RESULTS: The areas under the ROC curves for the FTQ, the
      FTND and the HSI were 0.71, 0.76 and 0.76 for the salivary cotinine and 0.71,
      0.79 and 0.80 for the exhaled CO respectively. The sensitivity and specificity of
      the FTND and the HSI were slightly greater than those for the FTQ. The optimum
      cutoff scores for the FTQ, the FTND and the HSI as screening tools to establish
      nicotine dependence would be 5+, 4+ and 3+ respectively. CONCLUSION: The results
      indicate that the FTND and the HSI may be more efficacious than the FTQ in
      assessing nicotine dependence. Further research is needed to confirm these
      findings, especially among female smokers and for nicotine substitution trials.
      Relevance to clinical practice. To decrease tobacco-attributable morbidity and
      mortality, nurses and healthcare professionals need to implement effective
      smoking cessation interventions. The FTND and the HSI as well as their cutoff
      scores will be suitably used to assess nicotine dependence in these
      interventions.

PMID- 18321288
TI  - An international Delphi study examining health promotion and health education in
      nursing practice, education and policy.
AB  - AIM: To arrive at an expert consensus in relation to health promotion and health
      education constructs as they apply to nursing practice, education and policy.
      BACKGROUND: Nursing has often been maligned and criticized, both inside and
      outside of the profession, for its ability to understand and conduct effective
      health promotion and health education-related activities. In the absence of an
      expert-based consensus, nurses may find it difficult to progress beyond the
      current situation. In the absence of any previously published nursing-related
      consensus research, this study seeks to fill that knowledge-gap. DESIGN: A two
      round Delphi technique via email correspondence. METHODS: A first-round
      qualitative questionnaire used open-ended questions for defining health promotion
      and health education. This was both in general terms and as participants believed
      these concepts related to the clinical, theoretical (academic/educational) and
      the policy (political) setting in nursing. Line-by-line qualitative content and
      thematic analysis of the first-round data generated 13 specific categories. These
      categories contained 134 statement items. The second-round questionnaire
      comprised the identified 134 statements. Using a five-point Likert scale (ranging
      from 1 = strongly disagree to 5 = strongly agree) participants scored and rated
      their level of agreement/disagreement against the listed items. Data from the
      second-round was descriptively analysed according to distribution and central
      tendency measures. RESULTS: An expert consensus was reached on 65 of the original
      134 statements. While some minor contradiction was demonstrated, strong consensus
      emerged around the issues of defining health promotion and health education and
      the emergence of a wider health promotion and health education role for nursing.
      No consensus was reached on only one of the 13 identified topic categories - that
      of 'nurses working with other disciplines and agencies in a health education and
      health promotion role.' CONCLUSIONS: This study provides a hitherto previously
      absent expert consensus on the current position of health promotion and health
      education, in nursing and predictions for their future course. Its findings
      represent an important step for nurses as they seek to become increasingly active
      and influential within wider health promotion and health education arenas.
      Relevance to clinical practice. Delphi studies do not necessarily offer
      indisputable fact. This study, however, with its strong consensus on the majority
      of original statements is a good indicator as to how nursing experts currently
      view health promotion and health education constructs. Expert consensus offers a
      useful form of measure against current and future clinical practice and helps to
      build a firm foundation for change. Nurses, then, are advised here to refer to
      the findings presented, that they remain contextually and conceptually clear, as
      they embark on current and future health promotion-related activities.

PMID- 18321289
TI  - An empowerment process: successful recovery from alcohol dependence.
AB  - AIMS: The purpose of this study was to explore the concepts and processes for
      successful abstinence from alcohol for Taiwanese Alcoholics Anonymous members.
      BACKGROUND: Attempting to identify the psychological and social influences upon
      alcohol consumption remission outside of alcoholism treatment could help
      professionals to engage in a broad array of community interventions in an
      informed fashion. METHODS: Grounded theory method was utilized in this study. The
      study chose nine participants who had succeeded in abstinence, using theoretical
      sampling and conducted in-depth interviews by an open-ended questionnaire.
      RESULTS: The results of this study indicated that the core of the process during
      which alcoholic individuals succeeded in abstaining from further alcohol
      consumption was an empowerment process for the involved individual. Alcoholics
      felt that their family, interpersonal relationships, jobs and personal finances
      all had been at 'rock-bottom' level following a long period of alcohol
      dependence. This feeling caused the individual to experience an emotion of a loss
      of control and provoked the arousal of an alcoholic's inner consciousness levels,
      this then resulting in the generation of a driving force for abstinence from
      alcohol for these individuals. CONCLUSIONS: The expansion of an individual's
      internal awakening power helps the individual to obtain assistance and to resist
      the temptation of further alcohol consumption. Therefore, the power derived by
      individuals from the stages of repositioning, releasing, active sharing,
      resistance and assistance are the maintenance factors for an individual's
      empowerment process that help maintain the successful recovery from alcohol for
      the involved individual. RELEVANCE TO CLINICAL PRACTICE: A good comprehension of
      the recovery processes for alcoholics, we believe, will trigger clinical
      professionals to pay appropriate attention to the specific problems and needs of
      alcoholic individuals, to build an effective resource network for treatment and
      to help solve alcoholics' physical and psychosocial problems.

PMID- 18321290
TI  - A causal model of contraceptive intention and its gender comparison among
      Taiwanese sexually inexperienced adolescents.
AB  - AIMS AND OBJECTIVES: To test latent constructs of social influences,
      contraceptive attitude and self-efficacy for contraception as a causal model of
      contraceptive intention among adolescents and to search for possible gender
      differences in the causal model of contraceptive intention. BACKGROUND: A greater
      understanding of the causal model of contraceptive intention among sexually
      inexperienced adolescents will help nurses design contraceptive programmes to
      improve adolescent contraceptive use when they have sex. Design. This was a cross
      sectional study; 770 boys and 685 girls that self-reported not being sexually
      experienced were selected for this study. METHODS: An anonymous questionnaire was
      used to collect data. By structural equation modelling using the eqs 6.1
      software, a hypothesized structural model of contraceptive intention was tested.
      FINDINGS: For both genders, social influences affected contraceptive intention
      indirectly through the contraceptive attitude and self-efficacy for
      contraception. Contraceptive attitude and self-efficacy for contraception
      affected contraceptive intention directly. Contraceptive attitude also affected
      contraceptive intention indirectly through the mediation of self-efficacy for
      contraception. There were gender differences in the variances of contraceptive
      intention explained by contraceptive attitude, self-efficacy for contraception
      and social influences. Nevertheless, the data explain only a low proportion of
      the variability in contraceptive intention. More causal constructs influencing
      contraceptive intention should be explored in future. CONCLUSIONS: Personal
      factors and social influences operate interdependently to influence contraceptive
      intention among sexually inexperienced adolescents. Gender is a moderator that
      can modify the influential level of social influences, contraceptive attitude and
      self-efficacy for contraception on contraceptive intention. RELEVANCE TO CLINICAL
      PRACTICE: Nurses should operate personal factors and social influences
      interdependently when they are designing intervention programmes for sexually
      inexperienced adolescents. To make intervention more effective, nurses also need
      to provide gender-specific intervention programmes for sexually inexperienced
      adolescents.

PMID- 18321291
TI  - Menopausal symptom perception and severity: results from a screening
      questionnaire.
AB  - BACKGROUND: Although it is widely acknowledged women experience symptoms during
      their transition from reproductive to postreproductive stage, there is
      inconsistency as to the prevalence of symptoms as well as their severity ratings.
      AIM AND OBJECTIVES: The purpose of this study was to describe symptom perception
      and severity in mid-life women volunteering for an intervention study for
      menopause symptom management. DESIGN: A cross-sectional descriptive design was
      used to provide data on presenting symptoms in a sample of women negotiating the
      menopausal transition. METHODS: A community-based sample of Caucasian women aged
      43-55 years was recruited from national nursing media, local media and a variety
      of local community sources. A screening questionnaire was administered to
      determine qualification for study entry based upon symptom severity scores from
      the questionnaire. This report includes results from the screening questionnaire.
      RESULTS: One hundred and sixty-five women were screened to obtain 110 qualified
      participants with mean age of 49.3 SD 3.04 years who were 4.7 SD 7 months past
      their last menstrual period. Sleep difficulties, forgetfulness and irritability
      were perceived by the highest number of women while sleep difficulties, night
      sweats, irritability and forgetfulness were rated the most severe. CONCLUSIONS:
      Findings from this study expand understanding of the menopause symptom
      experience, because few reports include symptom severity reports. All aspects of
      the symptom experience are necessary to develop appropriate interventions and to
      evaluate them. RELEVANCE TO CLINICAL PRACTICE: Providing education about
      menopause symptoms is central to nursing practice of mid-life women. Therefore,
      nurses must keep abreast of current knowledge to prepare women for their
      transition to postreproductive phase or to reassure women who are surprised to
      find hot flashes are not the only symptoms encountered.

PMID- 18321292
TI  - Related factors in using a free breastfeeding hotline service in Taiwan.
AB  - AIMS: This study aimed to examine the use of a free hotline service for
      breastfeeding mothers in Taiwan. Specific attention was given to the accumulated
      consultation time and to investigate the trends and reasons that prompted people
      to contact the service. BACKGROUND: Breastfeeding can be a difficult time for
      mothers, especially during the first two weeks after birth. It has been suggested
      that a telephone hotline service may be helpful for breastfeeding mothers.
      DESIGN: In this quantitative study data, including the demographic data and the
      problems of consultations, were gathered from callers during August 2003 to
      August 2005. RESULTS: Of the 2445 callers, 935 made subsequent calls (38.2%).
      Approximately 25.25 calls were answered each day by two specially-trained staff
      according to an answering book. The mean consultation time for single first-call
      was 21.82 minutes and for one subsequent-call was 15.87 minutes. Perceived
      insufficient milk supply (30%) and returning to work (21%) were the top two
      reasons for a first-call. If callers' problems were about babies' sickness,
      perceived insufficient milk supply, babies' body weight gain and supplement
      issues, the accumulated consultation time would last longer. More than half
      (53.3%; 1303/2445) of callers made the first-call during the first month after
      birth, followed by 23.2% (566/2445) during babies' age between one and three
      months old. CONCLUSION: The telephone hotline service for breastfeeding mothers
      in Taiwan was well used during the two year period of this study. Many mothers
      used the service repeatedly for a variety of reasons. RELEVANCE TO CLINICAL
      PRACTICE: Recommendations for breastfeeding support strategies for the
      professionals include category of common breastfeeding problems by different
      stages after birth. This study supports the establishment of free hotline
      services may encourage greater empowerment in breastfeeding mothers. Future
      studies are required to examine client satisfaction of the telephone service.

PMID- 18321293
TI  - Understanding eating behaviours in Spanish women enrolled in a weight-loss
      treatment.
AB  - AIM: To identify the beliefs and attitudes of a sample of obese and overweight
      Spanish women undertaking a weight-loss treatment. BACKGROUND: Obesity is a
      global epidemic. Weight-loss treatments focus on changing eating behaviours;
      however, many patients fail to adhere to the diet. This suggests that more
      effective behaviour-change interventions are required to help people change their
      eating behaviours. According to the theory of planned behaviour (TPB) human
      behaviour is influenced by beliefs. Identification of people's beliefs is an
      essential step in the design of behaviour-change interventions. DESIGN: A
      qualitative approach was employed using semi-structured interviews to interview
      participants. Seventeen obese and overweight Spanish women enrolled in a weight
      loss treatment were recruited using a criterion sample strategy. FINDINGS:
      Participants' reported beliefs referring to the benefits of losing weight and the
      emotions related to dieting. The more positive these beliefs were the more
      positive their attitude towards the diet seemed to be. Findings highlight the
      importance of follow-ups in creating a subjective norm to maintain a diet.
      Perceived behavioural control to diet seemed to be related to beliefs about
      social support; whereas beliefs about lack of willpower to overcome temptations
      seemed to decrease perceived control over eating behaviours. CONCLUSIONS:
      Participants reported several beliefs and attitudes that offer plausible
      explanations of their eating behaviours. Data from this study seemed to fit the
      propositions of the TPB and could be used in further research to develop
      effective eating behaviour-change interventions. RELEVANCE TO CLINICAL PRACTICE:
      Nurses could use the TPB to assess individuals' attitudes, beliefs and
      expectations when following a diet. That assessment would provide insight into
      what aspects are relevant for individual patients when dieting, which could lead
      to more effective diet behaviour-change interventions being designed.

PMID- 18321294
TI  - Community-based epidemiological study on breastfeeding and associated factors
      with respect to postpartum periods in Taiwan.
AB  - AIMS: To explore the prevalence of breastfeeding in different geographical areas
      and identify the factors influencing breastfeeding practices during in-hospital
      stay and at one, four and six months postpartum in Taiwan. BACKGROUND: The
      national data on prevalence for breastfeeding patterns are still unknown. DESIGN:
      Community-based epidemiological survey design. METHODS: A total of 12,201 women
      were sampled from the birth registration and surveyed between June-October 2004.
      Data were collected through a computer-assisted telephone interview at four
      different postpartum periods. Logistic regression modelling was applied to
      determine factors influencing breastfeeding patterns and postpartum time-specific
      odds ratios. RESULTS: Rates of breastfeeding practices were 29.4, 33.2, 16.9 and
      13.1% for in-hospital stay, the first-, fourth- and sixth-month postpartum
      respectively. Mother's intention to breastfeed was the most important factor to
      lengthen breastfeeding practices over time. The effect of an advocate programme
      in the hospital was significantly associated with breastfeeding only at the time
      of in-hospital stay. Age, family support and singleton were found to be
      significantly related to the continuation of breastfeeding at the fourth month
      postpartum. Employment status was significantly associated with the termination
      of breastfeeding, particularly at the later postpartum period. Geographical
      variation in breastfeeding practices within the first month postpartum was
      identified. In contrast, ethnic variation was more apparent at the later
      postpartum period. CONCLUSIONS: This large-scale study revealed a significantly
      decreasing trend after one month postpartum of breastfeeding rate in each
      geographical area of Taiwan. Factors associated with women's decision and
      continuation on breastfeeding patterns tended to be dependent on the time
      specific postpartum period and varied between geographical areas. RELEVANCE TO
      CLINICAL PRACTICE: If breastfeeding rates are to increase, more attention should
      be paid to establish early breastfeeding and counter the negative influences of
      factors within the social environment.

PMID- 18321295
TI  - Commentary on Takase M, Maude P & Manias E (2006) The impact of role discrepancy
      on nurses' intention to quit their jobs. Journal of Clinical Nursing 15, 1071
      1080.

PMID- 18321297
TI  - Equipoise, H. pylori, and Musketeers - choosing an appropriate standard clinical
      care regimen.

PMID- 18321298
TI  - Four modes of adhesion are used during Helicobacter pylori binding to human
      mucins in the oral and gastric niches.
AB  - BACKGROUND: Helicobacter pylori causes peptic ulcer disease and gastric cancer,
      and the oral cavity is likely to serve as a reservoir for this pathogen. We
      investigated the binding of H. pylori to the mucins covering the mucosal surfaces
      in the niches along the oral to gastric infection route and during gastric
      disease and modeled the outcome of these interactions. MATERIALS AND METHODS: A
      panel of seven H. pylori strains with defined binding properties was used to
      identify binding to human mucins from saliva, gastric juice, cardia, corpus, and
      antrum of healthy stomachs and of stomachs affected by gastritis at pH 7.4 and
      3.0 using a microtiter-based method. RESULTS: H. pylori binding to mucins
      differed substantially with the anatomic site, mucin type, pH, gastritis status,
      and H. pylori strain all having effect on binding. Mucins from saliva and gastric
      juice displayed the most diverse binding patterns, involving four modes of H.
      pylori adhesion and the MUC5B, MUC7, and MUC5AC mucins as well as the salivary
      agglutinin. Binding occurred via the blood-group antigen-binding adhesin (BabA),
      the sialic acid-binding adhesin (SabA), a charge/low pH-dependent mechanism, and
      a novel saliva-binding adhesin. In the healthy gastric mucus layer only BabA and
      acid/charge affect binding to the mucins, whereas in gastritis, the BabA/Le(b)
      dependent binding to MUC5AC remained, and SabA and low pH binding increased.
      CONCLUSIONS: The four H. pylori adhesion modes binding to mucins are likely to
      play different roles during colonization of the oral to gastric niches and during
      long-term infection.

PMID- 18321299
TI  - Leptin receptor signaling is required for vaccine-induced protection against
      Helicobacter pylori.
AB  - BACKGROUND: A vaccine against Helicobacter pylori would be a desirable
      alternative to antibiotic therapy. Vaccination has been shown to be effective in
      animal models but the mechanism of protection is poorly understood. Previous
      studies investigating the gene expression in stomachs of vaccinated mice showed
      changes in adipokine expression correlated to a protective response. In this
      study, we investigate a well-characterized adipokine-leptin, and reveal an
      important role for leptin receptor signaling in vaccine-induced protection.
      MATERIALS AND METHODS: Leptin receptor signaling-deficient (C57BL/Ks Lepr(db)),
      wild-type C57BL/Ks m littermates and C57BL/6 mice were vaccinated, and then
      challenged with H. pylori. Levels of bacterial colonization, antibody levels, and
      gastric infiltrates were compared. The local gene expression pattern in the
      stomach of leptin receptor signaling-deficient and wild-type mice was also
      compared using microarrays. RESULTS: Interestingly, while vaccinated wild-type
      lean C57BL/6 and C57BL/Ks m mice were able to significantly reduce colonization
      compared to controls, vaccinated obese C57BL/Ks Lepr(db) were not. All mice
      responded to vaccination, i.e. developed infiltrates predominantly of T
      lymphocytes in the gastric mucosa, and made H. pylori-specific antibodies. A
      comparison of expression profiles in protected C57BL/6 and nonprotected C57BL/Ks
      Lepr(db) mice revealed a subset of inflammation-related genes that were more
      strongly expressed in nonprotected mice. CONCLUSIONS: Our data suggest that
      functional leptin receptor signaling is required for mediating an effective
      protective response against H. pylori.

PMID- 18321300
TI  - NMR-based metabonomics for detection of Helicobacter pylori infection in gerbils:
      which is more descriptive.
AB  - BACKGROUND: Helicobacter pylori, the human pathogenic gram-negative
      microaerophilic bacterium, causes chronic gastric infection in more than half of
      the human population regardless of race. The infection of microbe is not yet
      controllable to pose a substantial public health impact and a growing social
      burden. The management of H. pylori infection primarily necessitates accurate and
      timely diagnosis at case level, on-demand supervision of pathologic progression,
      and reliable evaluation of the impact of pharmacologic interventions on the
      patients' population. METHODS: The characterization of H. pylori infection on
      gerbils model was performed by metabolic profiling, employing 1H NMR spectroscopy
      compounding multivariate pattern recognition strategies. In the same manner,
      urine samples were individually collected from 10 gerbils infected with H. pylori
      GS13, and from 10 uninfected control animals equally accessible to feed and
      water. RESULTS: The resultant metabolic profiles indicate that H. pylori
      infection disturbs carbohydrate metabolism to elevate the levels of alpha- and
      beta-glucose, and cis-aconitate (a TCA cycle intermediate). In addition to the
      energy metabolism alteration, the colonization of H. pylori in gerbil stomach
      generates a remarkable deviation of amino acid metabolism as indicated by
      depletion of taurine and arginine, and elevation of proline and glutamine in the
      animal urine. Moreover, the H. pylori infection modifies the gut microbiota as
      highlighted by a range of microbial-related metabolites such as indoxyl sulfate
      and hippurate. CONCLUSIONS: These findings demonstrate that the (1)H NMR-based
      urine metabolic profiling is a promising technique capable of providing an
      accurate, noninvasive, and rapid diagnosis of H. pylori infection.

PMID- 18321301
TI  - Helicobacter pylori and antrum erosion-specific gene expression patterns: the
      discriminative role of CXCL13 and VCAM1 transcripts.
AB  - BACKGROUND AND AIMS: Chronic Helicobacter pylori infection affects approximately
      half of the world, leads to chronic gastritis and peptic ulceration, and is
      linked to gastric carcinoma. Our aims were to compare the gene expression profile
      (GEP) of H. pylori-positive and H. pylori-negative gastric erosions and adjacent
      mucosa to explain the possible role and response to H. pylori infection and to
      get erosion-related mRNA expression patterns. METHODS: Total RNA was extracted,
      amplified, and biotinylated from gastric biopsies of patients with H. pylori
      positive and H. pylori-negative antrum erosions (ER) (8/8) and adjacent
      macroscopically normal mucosae (8/8). The GEP was evaluated using HGU133plus2.0
      microarrays. Two independent normalizations (MAS5.0, RMA), PAM feature selection,
      hierarchical cluster analysis, and discriminant analysis were done. The
      expression of 14 genes was also measured by real-time-polymerase chain reaction.
      VCAM-1 and CXCL13 immunohistochemistry (IHC) was done. RESULTS: In H. pylori
      infection, significant overexpression of MHC class II antigen-presenting genes,
      interleukin-7 receptor, ubiquitin-D, CXCR4, lactoferrin immune response-related
      genes, CXCL-2 and -13, CCL18 chemokine ligand, and VCAM-1 genes were established.
      In erosive gastritis, increased proliferation (MET) and transport (UCP2, SCFD1,
      KPNA4) were found, while genes associated with adhesion (SIGLEC11), transcription
      regulation (ESRRG), and electron and ion transport (ACADM, CLIC6) were down
      regulated. Discriminant analysis successfully classified all samples into four
      groups (HP+ER-, HP+ER+, HP-ER+, HP-ER-) using a reduced gene set (20).
      Significant overexpression of VCAM-1 and CXC13 protein was detected by IHC in HP+
      samples (p < .05). CONCLUSIONS: Whole genomic microarray analysis yielded new H.
      pylori infection and erosion-related gene expression changes. Discriminative
      genes can be used in mRNA-based diagnostic classification of gastric biopsies.

PMID- 18321302
TI  - Inhibition of Helicobacter pylori infection in humans by Lactobacillus reuteri
      ATCC 55730 and effect on eradication therapy: a pilot study.
AB  - BACKGROUND: Several studies report an inhibitory effect of probiotics on
      Helicobacter pylori. AIM: To test whether Lactobacillus reuteri ATCC 55730
      reduces H. pylori intragastric load in vivo, decreases dyspeptic symptoms, and
      affects eradication rates after conventional treatment. MATERIALS AND METHODS: In
      a double-blind placebo-controlled study, 40 H. pylori-positive subjects were
      given L. reuteri once a day for 4 weeks or placebo. All underwent upper
      endoscopy, (13)C-urea breath test, and H. pylori stool antigen determination at
      entry and (13)C-urea breath test and H. pylori stool antigen (used as both
      qualitative and semiquantitative markers) after 4 weeks of treatment. Sequential
      treatment was administered subsequently to all. RESULTS: In vivo, L. reuteri
      reduces H. pylori load as semiquantitatively assessed by both (13)C-urea breath
      test delta-value and H. pylori stool antigen quantification after 4 weeks of
      treatment (p < .05). No change was shown in patients receiving placebo. L.
      reuteri administration was followed by a significant decrease in the
      Gastrointestinal Symptom Rating Scale as compared to pretreatment value (p < .05)
      that was not present in those receiving placebo (p = not significant). No
      difference in eradication rates was observed. CONCLUSIONS: L. reuteri effectively
      suppresses H. pylori infection in humans and decreases the occurrence of
      dyspeptic symptoms. Nevertheless, it does not seem to affect antibiotic therapy
      outcome.

PMID- 18321303
TI  - Helicobacter pylori genotyping and sequencing using paraffin-embedded biopsies
      from residents of colombian areas with contrasting gastric cancer risks.
AB  - BACKGROUND: cagA-positive and vacA s1 and m1 genotypes of Helicobacter pylori are
      associated with an elevated risk of gastric cancer (GC). We determined these
      genotypes using paraffin-embedded gastric biopsy specimens harvested from
      infected individuals and compared genotype distributions in two Colombian
      populations residing in geographic regions with a high and low incidence of GC.
      METHODS: DNA from paraffin-embedded gastric biopsies from 107 adults was
      amplified using primers specific for cagA, for the cag'empty site', for the s and
      m alleles of vacA, and for H. pylori 16S rRNA. RESULTS: H. pylori infection was
      detected by molecular assays in 97 (90.7%) biopsies. Complete genotyping of cagA
      and vacA was achieved in 94 (96.9%) cases. The presence of cagA was detected in
      78 of 97 cases (80.4%); when considered separately, cagA and vacA s regions were
      not significantly associated with a particular geographic area. The vacA m1
      allele and s1m1 genotypes were more common in the area of high risk for GC (p =
      .037 and p = .044, respectively), while the vacA m2 allele and s2m2 genotypes
      were more prevalent in the low-risk area. The prevalence of the combination of
      cagA-positive, vacA s1m1 genotypes was 84.3% and 60.5% for high and low risk
      areas, respectively (p = .011). CONCLUSIONS: H. pylori cagA and vacA genotyping
      from paraffin-embedded gastric biopsies permitted reliable typability and
      discrimination. The more virulent cagA-positive s1m1 strains, as well as vacA m1
      genotype, were more prevalent in high risk than in low risk areas, which may
      contribute to the difference in GC risk between those two regions.

PMID- 18321304
TI  - The role of serum pepsinogen and gastrin test for the detection of gastric cancer
      in Korea.
AB  - BACKGROUND AND AIM: This study was performed to determine whether serum
      pepsinogen (PG) and gastrin testing can be used to detect gastric cancer in
      Korea. METHODS: Serum levels of PG I (sPGI) and sPGII, PG I/II ratios, and
      gastrin levels were measured in 1006 patients with gastroduodenal diseases
      including cancer. Follow-up tests were performed 1 year after Helicobacter pylori
      eradication. RESULTS: sPGI and sPGII levels increased and PG I/II ratios
      decreased in line with the severity of activity, chronic inflammation, and the
      presence of H. pylori (p < .01). In contrast, sPGI levels and PG I/II ratios
      decreased in proportion with the severity of atrophic gastritis (AG)/intestinal
      metaplasia (p < .01). Gastrin levels were found to be correlated with chronic
      inflammation negatively in the antrum but positively in the corpus. H. pylori
      eradication reduced sPGI, sPGII, and gastrin levels, and increased PG I/II ratios
      to the levels of H. pylori-negative patients, and was found to be correlated with
      reductions in activity and chronic inflammation of gastritis. The sensitivity and
      specificity of a PG I/II ratio of < or = 3.0 for the detection of dysplasia or
      cancer were 55.8-62.3% and 61%, respectively. In addition, sPGI and sPGII levels
      of intestinal-type cancer were significantly lower than those of the diffuse
      type, respectively (p = .008 and p = .05, respectively). Gastric cancer risk was
      highest in the H. pylori-positive, low PGI/II ratio (< or = 3.0) group with an
      odds ratio of 5.52 (confidence interval: 2.83-10.77). CONCLUSION: PG I/II ratio
      (< or = 3.0) was found to be a reliable marker for the detection of dysplasia or
      gastric cancer, especially of the intestinal type. This detection power of PG
      I/II ratio (< or = 3.0) significantly increased in the presence of H. pylori, and
      thus, provides a means of selecting those at high risk of developing gastric
      cancer in Korea.

PMID- 18321305
TI  - Prevalence and risk factors for Helicobacter pylori infection in Chinese
      populations.
AB  - BACKGROUND: The prevalence of Helicobacter pylori is higher in developing
      countries. The aim of this study was to investigate the prevalence and risk
      factors of H. pylori infection in areas with high prevalence of gastric cancer in
      Jiangsu Province, China. METHODS: A prospective epidemiologic survey of H. pylori
      infection was accomplished in a natural population of 1457 individuals in
      Xiangshui and Gaoyou counties, Jiangsu Province, China. Questionnaires and
      laboratory tests for H. pylori infection ((13)C-urea breath test and serum IgG
      antibodies to H. pylori) were used and performed, respectively. RESULT: Among
      1371 subjects who completed questionnaires and H. pylori detection, 851 (62%)
      were H. pylori positive. The prevalence reached a peak at the age of 30-40 years
      (67%). There was no sex difference. The annual family income level was shown to
      be positively correlated with the risk of H. pylori infection. The prevalence of
      H. pylori infection was also associated with family size, education level, and
      several diet-related factors, such as the number of times cooked rice and
      potatoes eaten per week, and a family history of stomach diseases. Compared to
      nonsymptomatic individuals, people with dyspeptic symptoms (nausea, vomiting, and
      belching) presented a low prevalence of H. pylori infection. No association
      between H. pylori prevalence and smoking or drinking was found. Using
      multivariate logistic regression analysis, annual family income and education
      level were the independent predictors for H. pylori infection. CONCLUSION: High
      prevalence of H. pylori infection was found in areas with a high risk of gastric
      cancer and was related to several risk factors. The underlying mechanisms need to
      be further investigated.

PMID- 18321306
TI  - Characterization of a candidate locus for malaria susceptibility in human
      populations: a (TA)n microsatellite in the promoter region of the CYBB gene, the
      gp91 phox subunit of the NADPH oxidase.
AB  - We have analysed the linkage disequilibrium pattern between the promoter TA
      microsatellite and Single Nucleotide Polymorphism (SNP) haplotypes for the CYBB
      gene. None of the CYBB SNPs serve as good surrogates for the microsatellite
      alleles, previously associated with mild malaria. Thus, the candidate (TA)(n)
      microsatellite should be directly tested in genetic epidemiology studies.

PMID- 18321307
TI  - The frequency of transforming growth factor-beta1 gene polymorphisms in a normal
      southern Iranian population.
AB  - Several single nucleotide polymorphisms (SNPs) of the transforming growth factor
      beta1 gene (TGFB1) have been reported. Determination of TGFB1 SNPs allele
      frequencies in different ethnic groups is useful for both population genetic
      analyses and association studies with immunological diseases. In this study, five
      SNPs of TGFB1 were determined in 325 individuals from a normal southern Iranian
      population using polymerase chain reaction-restriction fragment length
      polymorphism method. This population was in Hardy-Weinberg equilibrium for these
      SNPs. Of the 12 constructed haplotypes, GTCGC and GCTGC were the most frequent in
      the normal southern Iranian population. Comparison of genotype and allele
      frequencies of TGFB SNPs between Iranian and other populations (meta-analysis)
      showed significant differences, and in this case the southern Iranian population
      seems genetically similar to Caucasoid populations. However, neighbour-joining
      tree using Nei's genetic distances based on TGF-beta1 allele frequencies showed
      that southern Iranians are genetically far from people from the USA, Germany, UK,
      Denmark and the Czech Republic. In conclusion, this is the first report of the
      distribution of TGFB1 SNPs in an Iranian population and the results of this
      investigation may provide useful information for both population genetic and
      disease studies.

PMID- 18321308
TI  - A search for cyclophilin-A gene (PPIA) variation and its contribution to the risk
      of atherosclerosis and myocardial infarction.
AB  - Cyclophilin A is secreted by vascular smooth muscle cells in response to
      inflammatory stimuli, and could thus contribute to atherosclerosis. We
      hypothesized that the genetic variation at the cyclophilin A gene (PPIA) could
      affect the risk for developing atherosclerosis and myocardial infarction. This
      study included 250 myocardial infarction patients (all male and < 60 years; 95%
      are smokers). All these cases had at least one atherosclerotic diseased coronary
      vessel. DNA was obtained from patients and from 250 healthy controls. The
      variation at the PPIA gene was determined in the patients through single-strand
      conformation analysis and direct sequencing of seven polymerase chain reaction
      fragments. Allele and genotype frequencies were compared between patients and
      controls. The effect of a promoter polymorphism (-11 G/C) on gene expression was
      in vitro analysed with luciferase-reporter assays. We found two common
      polymorphisms in the PPIA promoter (-11 G/C) and the 5' non-translated (+36 G/A)
      regions. Cells transfected with luciferase-plasmids containing the -11 G had
      significantly higher luciferase activity. Genotype frequencies for these
      polymorphisms did not differ between patients and controls. In conclusion, we
      reported a functional variant in the PPIA promoter. However, the PPIA variation
      did not significantly contribute to the risk of suffering from myocardial
      infarction among patients with atherosclerotic diseased vessels.

PMID- 18321309
TI  - Association of interleukin-1 receptor antagonist +2018 gene polymorphism with
      Japanese chronic periodontitis patients using a novel genotyping method.
AB  - Genetic variants at multiple loci have been shown to be associated with
      periodontitis risk. In this study, we have focused on nine functional gene
      polymorphisms encoding immunoregulation-related molecules such as cytokines
      (interleukin-1 (IL-1), transforming growth factor-beta1 (TGF-beta1)) and cell
      surface receptors (immunoglobulin G and A Fc receptors (Fc gamma R and Fc alpha
      R)). In total, 113 Japanese patients with chronic periodontitis (CP) and 108 race
      matched healthy controls were genotyped with the modified serial invasive signal
      amplification reaction. There was a significant difference in the distribution of
      IL-1 receptor antagonist (RN) +2018 T/C allele between the patient and control
      groups, with enrichment of the +2018 C in controls (P = 0.021, odds ratio =
      0.38). An increased frequency of the IL-1 haplotype comprising IL-1A +4845 G, IL
      1B -31 C, and IL-1RN +2018 C was observed in controls (P = 0.004). Moreover, a
      multivariate logistic regression analysis revealed that subjects with IL-1RN
      +2018 C allele were less likely to have CP (P = 0.016, odds ratio = 0.29). These
      findings document the association of IL-1RN +2018 C with reduced susceptibility
      to CP in the Japanese.

PMID- 18321311
TI  - FingerTip Urology: illustrations for patient dialogue at the click of your
      cursor.

PMID- 18321312
TI  - A conversation between Darracott Vaughan and Tim Ratliff.

PMID- 18321313
TI  - Achieving effective risk-factor modification in urological patients.

PMID- 18321314
TI  - Tyrol Prostate Cancer Demonstration Project: early detection, treatment, outcome,
      incidence and mortality.
AB  - OBJECTIVE: To evaluate the effectiveness of a well-controlled programme of early
      detection and treatment of prostate cancer in the population of Tyrol, Austria,
      where such a programme of early detection and treatment was initiated in 1988 and
      where prostate-specific antigen (PSA) testing was offered for free to all men
      aged 45-75 years from 1993. SUBJECTS AND METHODS: Comparison of prostate cancer
      mortality rates in Tyrol and the rest of Austria was accomplished through a
      generalized additive model. A piecewise linear change-point Poisson regression
      model was used to compare mortality rates in Tyrol and the rest of Austria.
      Standardized mortality ratios were calculated with reference to the mortality
      rates in 1986-1990. RESULTS: In all, 86.6% of eligible men have been tested at
      least once since 1993. Cancer deaths in Tyrol in 2005 were 54% (95% confidence
      interval [CI] 34-69%) lower than expected compared with 29% (95% CI 22-35%) in
      the rest of Austria. The decreasing trend in prostate cancer mortality was
      significantly greater in Tyrol compared with the rest of Austria (P = 0.001). A
      significant migration to lower stage disease occurred and radical prostatectomy
      was associated with low morbidity. CONCLUSIONS: In the Tyrol region where
      treatment is freely available to all patients, where widespread PSA testing and
      treatment with curative intent occurs, there was a reduction in prostate cancer
      mortality rates which was significantly greater than the reduction in the rest of
      Austria. This reduction in prostate cancer mortality is most probably due to
      early detection, consequent down-staging and effective treatment of prostate
      cancer.

PMID- 18321315
TI  - Is the utility of prostate-specific antigen velocity for prostate cancer
      detection affected by age?
AB  - OBJECTIVE: To determine whether prostate-specific antigen velocity (PSAV) is
      useful for prostate cancer detection in men from different age groups, and
      whether the same PSAV thresholds can reasonably be applied to all men aged >or=40
      years. PATIENTS AND METHODS: From a large prostate cancer screening study, 13,615
      men had data on age and a calculable PSAV. We used statistical analysis to
      examine the ability of PSAV to predict prostate cancer risk in each age decade.
      RESULTS: For men of all ages, the median PSAV was 0.6-0.7 ng/mL/year in men with
      prostate cancer, and 0-0.1 ng/mL/year in men with no prostate cancer (P < 0.005
      for all). On receiver operating characteristic (ROC) analysis, the area under the
      curve was 0.800, 0.697, 0.693, and 0.668 for predicting prostate cancer risk
      using PSAV for men aged 40-49, 50-59, 60-69 and >or=70 years, respectively. In
      the multivariate model controlling for race, family history, and the total PSA
      level, both PSA and PSAV were significant independent predictors of prostate
      cancer risk in men of all ages. CONCLUSIONS: The PSAV is significantly higher in
      men of all ages with prostate cancer compared with men with no prostate cancer;
      although on ROC analysis it performed the best in young men. Interestingly, the
      median PSAV in men with prostate cancer was <0.75 ng/mL/year regardless of age,
      suggesting that this threshold may be too high. Overall, this data confirms that
      PSAV is a useful tool for prostate cancer detection for men aged >or=40 years.

PMID- 18321316
TI  - The effect of surgical volume, age and comorbidities on 30-day mortality after
      radical prostatectomy: a population-based analysis of 9208 consecutive cases.
AB  - OBJECTIVES: To examine the effect of surgical volume (SV) on 30-day mortality
      after radical prostatectomy (RP; reportedly 0.1-0.6% and influenced by age and
      comorbidities) and to explore the most informative SV, age and comorbidity
      thresholds to distinguish between high- and low-risk men. PATIENTS AND METHODS:
      Between 1989 and 2000, 9208 consecutive patients were treated with RP. The
      effects on 30-day mortality of (either continuously coded or categorized) patient
      age, comorbidities (Charlson Comorbidity Index, CCI) and SV were tested in
      multivariable logistic regression models. The models were corrected for overfit
      bias using 200 bootstrap re-samples and were displayed graphically as nomograms.
      RESULTS: The overall 30-day mortality was 0.52%; being younger (<69 years, 0.3%
      vs 1.0% 30-day mortality otherwise, P < 0.001), lower CCI (0, 0.2% vs 0.8%
      otherwise, P < 0.001) and higher SV (>27 RPs, 0.07 vs 0.6% otherwise, P = 0.049)
      had a protective effect and represented independent predictors of 30-day
      mortality. After correction for overfit bias, their combined input was 72.3%
      accurate in predicting 30-day mortality, vs 67.1% (P < 0.001) when the same
      variables were used in continuously coded (uncategorized) format. A model-derived
      probability threshold of <or=0.1% resulted in a 99.9% negative predictive value.
      CONCLUSIONS: SV is an important determinant of 30-day mortality. Categorized age,
      CCI and SV are more useful and more accurate for predicting 30-day mortality than
      continuously coded variables. The combination of young age (<69 years), a CCI of
      0 and high SV (>27 RPs) can accurately identify patients at negligible risk of 30
      day mortality.

PMID- 18321317
TI  - Alfuzosin 10 mg once daily for treating benign prostatic hyperplasia: a 3-year
      experience in real-life practice.
AB  - OBJECTIVES: To assess the 3-year efficacy and safety of the selective alpha(1)
      blocker alfuzosin at 10 mg once daily in men with lower urinary tract symptoms
      (LUTS) suggestive of benign prostatic hyperplasia (BPH) in 'real-life practice'.
      The influence of treatment response on the risk of acute urinary retention (AUR)
      and BPH-related surgery was also analysed. PATIENTS AND METHODS: In all, 689
      European men (mean age 67.6 years) were enrolled by general practitioners in a 3
      year open-label study with alfuzosin at 10 mg once daily. They were asked to
      complete the International Prostate Symptom Score (IPSS), its eighth question
      (bother score), and the Danish Prostatic Symptom Score for sexual function (DAN
      PSSsex). Efficacy was analysed at the endpoint in the intent-to-treat population.
      The impact of baseline variables (age, PSA level, IPSS and bother severity) and
      dynamic variables (IPSS worsening of >or=4 points and bother at the last
      available assessment under treatment) on the risk of AUR and BPH-related surgery
      was evaluated. RESULTS: With alfuzosin, IPSS improved by 6.4 points (-33.4%) from
      baseline (P < 0.001), reaching >or=3 points and >6 points in 71.3% and 47.2% of
      men, respectively. There were also significant (P < 0.001) improvements from
      baseline in nocturia (-0.8, -25.5%), bother score (-1.7, -40.7%) and DAN-PSSsex
      weighted scores with treatment. Symptom relief was rapid and maintained over 3
      years. Overall, 78 men (12.4%) had an IPSS worsening of >or=4 points, 16 (2.6%)
      had AUR, and 36 (5.7%) required BPH-related surgery. Symptom deterioration during
      treatment and high baseline PSA values were the best predictors of AUR and BPH
      related surgery. Alfuzosin was well tolerated, dizziness being the most frequent
      adverse event (4.5%) possibly related to vasodilatation. Ejaculatory disorders
      were uncommon (0.4%). Changes in blood pressure remained marginal, including in
      men aged >or=65 years and those receiving antihypertensive agents. CONCLUSION:
      Alfuzosin administered for 3 years at 10 mg once daily in real-life practice is
      effective and well tolerated. High PSA values and symptom worsening under
      treatment appear the best predictors of AUR and BPH-related surgery in the long
      term. Treatment with alfuzosin might thus help to identify patients at risk of
      LUTS/BPH progression in order to optimize their management.

PMID- 18321318
TI  - Laparoscopic renal surgery in the octogenarian.
AB  - OBJECTIVE: To describe our experience with laparoscopic renal surgery (LRS) in
      the octogenarian. Octogenarians are generally suboptimal surgical candidates but
      the recent upsurge of minimally invasive options for the management of kidney
      lesions, such as laparoscopic excision, cryoablation and radiofrequency ablation
      (RFA), have changed that perception. PATIENTS AND METHODS: In all, 26 patients
      aged >or=80 years underwent LRS at Brown University and the University of
      Wisconsin between 2000 and 2006. Demographic information, anatomical location,
      tumour stage, comorbidities, type of laparoscopic approach, management and
      outcomes were assessed. Complications during and after LRS, hospital stay,
      analgesia requirements and return to normal activity were analysed. RESULT: The
      mean age of the patients was 81 years. The procedures performed included hand
      assisted laparoscopic partial nephrectomy (three patients), hand-assisted
      laparoscopic radical nephrectomy (10), hand-assisted laparoscopic
      nephroureterectomy (four), laparoscopic-assisted cryoablation (seven),
      laparoscopic RFA (one), and laparoscopic unroofing of a renal cyst (one). The
      mean (range) follow-up was 40 (8-84) months. The mean American Society of
      Anesthesiologists score was 2.5. The average hospital stay was 5.6 days and the
      mean time to normal activity after discharge was 19 days. There were two major
      and five minor complications. Nineteen of 22 patients evaluable had no evidence
      of disease at the last follow-up. The three deceased patients died of unrelated
      causes. CONCLUSION: LRS in the octogenarian is safe to perform in patients with
      multiple comorbidities. The major and minor complication rates were 7% and 19%,
      respectively. Recent trends show that ablative procedures are being performed
      more commonly than surgical excision in this age group.

PMID- 18321319
TI  - Total reconstruction of the vesico-urethral junction.
AB  - OBJECTIVE: We describe a novel technique of total vesico-urethral reconstruction,
      which combines the tactics of previous surgeons, and compare the outcome of our
      innovative changes for return to early continence with prostatectomies with no or
      partial reconstruction of the vesico-urethral junction. PATIENTS AND METHODS:
      Between 1 January 2005 and 5 June 2007 a cohort of 700 patients undergoing
      robotic radical prostatectomy were prospectively evaluated. Patients in 2005
      (214) served as a control group, they received no additional methods to provide
      support to the vesico-urethral junction; a standard anastomosis was made.
      Patients in 2006 (304) received an anterior reconstruction only, to provide
      additional vesico-urethral anastomotic support. Patients in 2007 (182) received
      the total reconstructive procedure, which included an anterior reconstruction and
      posterior reconstruction. Outcome data were collected using standardized health
      related quality-of-life measures, which included the Expanded Prostate Cancer
      Index Composite survey, International Prostate Symptom Score, International Index
      of Erectile Function, and then re-verified by telephone interview with a
      standardized questionnaire. The follow-up intervals were 1, 6, 12, 24 and 52
      weeks. Continence was defined as no pad usage or one small liner used for
      security purposes only. Baseline variables were also collected. RESULTS: The
      percentage of patients who had achieved continence in the control group were:
      13%, 35%, 50%, 62% and 82% at the 1-, 6-, 12-, 24- and 52-week follow-up,
      respectively. The percentage of patients who had achieved continence in the
      anterior reconstruction group were 27%, 59%, 77%, 86%, and 91%, respectively. The
      total reconstruction group had continence rates of 38%, 83%, 91%, and 97% at 1,
      6, 12, and 24 weeks, respectively. At all the follow-up intervals the continence
      rate was significantly less in the control group than in the anterior
      reconstruction group and the total reconstruction group (P < 0.01). CONCLUSIONS:
      The total reconstruction procedure is a safe and effective way to achieve an
      early return to continence. No adverse effects have been observed because of its
      employment and our data validates that it does provide a statistically
      significant early return to continence compared with no reconstructive efforts or
      with only anterior reconstructive efforts.

PMID- 18321320
TI  - It's been a long time coming, but that's good.

PMID- 18321323
TI  - Re: Outcome after cytoreductive nephrectomy for metastatic renal cell carcinoma
      is predicted by fractional percentage of tumour volume removed.

PMID- 18321324
TI  - Nerve-sparing endoscopic extraperitoneal radical prostatectomy.

PMID- 18321325
TI  - Sexual politics, torture, and secular time.

PMID- 18321326
TI  - The times of movements: a response.

PMID- 18321327
TI  - Troubling times: a comment on Judith Butler's 'Sexual politics, torture and
      secular time'.

PMID- 18321328
TI  - Secularism and coercive freedoms.

PMID- 18321329
TI  - A basis for and two obstacles in the way of a multiculturalist coalition.

PMID- 18321330
TI  - Secular privilege, religious disadvantage.

PMID- 18321331
TI  - Life in the fast lane? Towards a sociology of technology and time.
AB  - Assumptions about the pace of life speeding up abound in contemporary social
      theory. While many factors are contributing to this phenomenon, information and
      communication technologies are seen as the main drivers. This article considers
      the way social theorists analyse the concepts of time and speed and then examines
      how these claims might be assessed in the light of empirical research. Such
      research shows that time compression has multiple dimensions, and that the effect
      of digital devices like the mobile phone is not simply one of acceleration. In
      particular, I suggest that the social studies of technology offers a richer
      analysis of the reciprocal relationship between technological innovation and
      changing time practices. My argument is that while the hitherto neglected
      temporal dimension in sociological theory is now being addressed, there is an
      urgent need for increased dialogue to connect social theory with detailed
      empirical studies. Without this, we will continue to have difficulty
      distinguishing social science from science fiction.

PMID- 18321332
TI  - The fourth shift: exploring the gendered nature of sleep disruption among couples
      with children.
AB  - The study of sleep has been neglected within sociology, yet may provide insights
      into fundamental aspects of the nature of gender inequalities. This article
      examines how, for couples with children, sleep is influenced by the gendered
      nature of caring. A key concern is not only who gets up to care for children's
      physical needs at night, but whether this changes with women's increased role in
      the labour market. Of concern also is how changes in the nature of caring for
      older children, as opposed to young children, may impact on parents' sleep. This
      article analyses qualitative data from an ESRC funded multi-disciplinary project
      on couples' sleep based on in-depth audio-tape recorded interviews with 26
      couples (aged 20-59) with younger and older children. Additionally, one week's
      audio sleep diaries were completed and follow up in-depth interviews were
      undertaken with each partner on an individual basis. Physical and emotional care
      for young children at night was largely provided by women, with a lack of
      explicit negotiation between partners about who provides this care, even when
      women return to employment. Thus, considerably more women than men continued
      their daytime and evening shifts, as well as undertaking an ongoing third shift
      of sentient activity for their family, into the night. This resulted in a fourth
      night-time shift where physical caring, and sentient activities continued. As a
      consequence, women were more likely to subjugate their own sleep needs to those
      of their family. Fathers did not, in general, undertake this fourth night-time
      shift. Those that did were more likely to be the fathers of young adult children
      who were staying out late at night, with the focus of their concerns being the
      safety of their children.

PMID- 18321333
TI  - Exploring commonality and difference in in-depth interviewing: a case-study of
      researching British Asian women.
AB  - This paper draws on the experience of researching British South Asian women's
      lives in London as a female British Asian researcher to explore how cultural
      commonality and difference is shaped by agency and interaction in the research
      process. It examines these issues through a discussion of how the shared cultural
      identity of the researcher and the interviewees emerged as both a point of
      commonality and difference in the research process; with the researcher being
      ;positioned' in terms of both as a result of the interviewees' agency in
      interpreting their cultural commonality. In particular, issues of 'Indianness'
      and religion emerged as points on which interviewees exercised agency and
      interpreted the researcher's cultural identity. This was the basis on which they
      claimed commonality or difference and this assessment consequently impacted on
      their interaction with the researcher. The article suggests that more attention
      needs to be given to how assumptions made by interviewees regarding the cultural
      identity of the researcher through their agency and interaction in the research
      process shapes interview dynamics.

PMID- 18321334
TI  - Our favourite melodies: musical consumption and teenage lifestyles.
AB  - The present study explores the determinants and lifestyle correletes of musical
      preferences among a large sample of high school students in Toronto, Ontario. Our
      work is informed by theory and research on cultural stratification and adolescent
      subcultures. In terms of cultural stratification, we engage with Bourdieu's
      (1984) and Peterson's (1996) conceptualizations of elite taste, while subcultural
      theory encourages us to focus upon more dissenting tastes and to explore
      connections between musical tastes and peer group activity. Our findings suggest
      that racial and ethnic identity, school experiences and cultural capital are
      significant sources of variation in musical tastes that loosely correspond to
      existing typologies; they also confirm what has often been inferred - that
      musical tastes and peer group cultural practices are closely linked. Our findings
      are then discussed in the light of current debates about the nature and
      dimensions of listening audiences for music.

PMID- 18321335
TI  - Being a pretty good citizen: an analysis and monetary valuation of formal and
      informal voluntary work by gender and educational attainment.
AB  - This paper is set in the context of macrosocial/macroeconomic theories of the
      organization of both paid and unpaid work. The specific topic investigated is
      engagement in unpaid voluntary work, an activity which is thought to be important
      for social cohesion, civil society and citizenship. Research on the sources of
      social cohesion has focused on organizational membership and voluntary
      organization activity. There has been little investigation of informal helping of
      non-resident kin, friends or acquaintances, an activity which is not measured in
      most social surveys but is measured in time use surveys. Previous research shows
      that the highly educated are more likely to engage in formal voluntary
      organizations and data from the UK 2000 HETUS survey confirm that the highly
      educated spend more time on formally organised voluntary work. However, the less
      qualified, particularly women, spend more time on extra-household unpaid helping
      activities. Since both types of voluntary work are partly dependent on available
      time, these findings are modelled adjusting for time allocated to paid work,
      study, family and personal care. The findings remain statistically significant.
      Drawing on work carried out by the Office for National Statistics, a monetary
      value is placed on both formally organized and informal voluntary work. Although
      the median wage rates for formal voluntary work are greater than those for
      informal helping, the latter is greater in frequency and duration and therefore
      more economically valuable from a population perspective. This finding is
      discussed in the light of recent debates on citizenship and gender.

PMID- 18321344
TI  - Orofacial granulomatosis: review on aetiology and pathogenesis.
AB  - Orofacial granulomatosis (OFG) is considered as an uncommon disease and
      nomenclature of the disease was subjected to debate for a long time. Although
      various aetiological agents such as food substances, food additives, dental
      materials and various microbiological agents have been implicated in the disease
      process its precise pathogenesis is yet to be elucidated. Delayed type of
      hypersensitivity reaction appears to play a significant role, although the exact
      antigen inducing the immunological reaction varies in individual patients.
      However, evidence for the role of genetic predisposition to the disease is
      sparse. The underlying immunological mechanism appears to show some similarities
      between OFG and Crohn's disease, emphasizing the need for more comparative
      studies of the two entities. Therefore, we propose the term idiopathic OFG as a
      better term for those cases restricted to oral region without any identifiable
      known granulomatous disease and the diagnosis should not be changed until the
      patient develops systemic manifestations of a specific granulomatous condition.
      This review attempts to discuss the role of different aetiological agents and
      certain aspects of pathogenesis of OFG.

PMID- 18321345
TI  - No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated
      with bisphosphonates.
AB  - BACKGROUND: Recent reports of osteonecrosis of the jaw (ONJ) after dental surgery
      in patients treated with second- and third-generation nitrogen-containing
      bisphosphonates instigated this retrospective study. As treatment with
      bisphosphonates in patients with osteogenesis imperfecta (OI) has become an
      important symptomatic therapy, especially for severe forms of the disease, we
      found it important to investigate whether healing after surgical exposure of jaw
      bone was influenced by the bisphosponate treatment in our group of children,
      adolescents and young adults with OI. SUBJECTS AND METHODS: Disodiumpamidronate
      was given as monthly intravenous infusion to 64 patients with OI aged 3 months to
      20.9 years at the start of treatment (mean 8.1, median 7.7). During 0.5-12.5
      years of treatment (mean 4.5, median 4.0), a total individual dose of 140-4020
      mg/m(2) disodiumpamidronate was given (mean 1623 and median 1460). Ten patients
      continued with oral alendronate and two with zoledronic acid therapy. In 22 of
      these patients, 38 dental surgery procedures were performed at the age of 3.4
      31.9 years (mean 12.2, median 12.3) after 0.03-7.9 years of treatment (mean 3.6,
      median 3.4). RESULTS: Despite long-term intravenous monthly disodiumpamidronate
      treatment, none of the 64 patients had any clinical signs of ONJ. CONCLUSIONS:
      The risk of ONJ in these patients must be considered so low that the patients
      with indications for treatment should be treated and get the chance to experience
      the well-documented beneficial effect for children with severe OI.

PMID- 18321346
TI  - Isolated gingival relapse of acute lymphoblastic leukemia after transplantation.
AB  - A patient with a history of precursor B-cell leukemia presented with an isolated
      ulcerating gum lesion 8 years after allogeneic stem cell transplantation with
      severe graft versus host disease. A biopsy revealed an undifferentiated malignant
      hemic lesion. Examinations of the peripheral blood and marrow were normal.
      Molecular studies confirmed clonal relationship between the gum lesion with the
      original marrow disease, despite the anatomical, histological and chronological
      separations.

PMID- 18321349
TI  - Recombinant early secreted antigen target 6 protein as a skin test antigen for
      the specific detection of Mycobacterium tuberculosis infection.
AB  - Although the delayed-type hypersensitivity skin test reaction to tuberculin
      purified protein derivative (PPD) is used worldwide for tuberculosis (TB)
      detection, it is incapable of distinguishing Mycobacterium tuberculosis (MTB)
      infection from bacille Calmette-Guerin (BCG) vaccination or infection with non
      tuberculous Mycobacteria. As a result, there is an urgent need for a more
      specific diagnostic tool for TB. This study reports the skin reactions of guinea
      pigs and human volunteers to recombinant early secreted antigen target 6
      (rESAT6), a secretory protein found only in MTB, M. bovis and few other
      mycobacterial species. These volunteers had varying histories of BCG vaccination
      and exposure to MTB, allowing us to determine the specificity of their response
      to TB exposure. Our results show that 1.0 microg of the purified MTB rESAT6
      antigen elicited a positive skin response in both animals and humans exposed to
      MTB, as well as in animals exposed to M. bovis and M. marinum, all species of
      Mycobacteria that contain the gene for early secreted antigen target 6 (ESAT6).
      ESAT6 appears to be more specific to MTB infection than PPD, as demonstrated by
      the fact that we saw no skin responses in the BCG-vaccinated volunteers, nor in
      the guinea pigs sensitized with BCG vaccine, or with Mycobacteria that do not
      contain the gene encoding ESAT6. We believe that this is the first report of the
      use of a rESAT6 protein in a skin test in human volunteers, and that these data
      support its use in the specific detection of MTB infection.

PMID- 18321350
TI  - Triggering receptor expressed on myeloid cells-1 (TREM-1) expression on gastric
      epithelium: implication for a role of TREM-1 in Helicobacter pylori infection.
AB  - In Helicobacter pylori gastritis gastric epithelium plays a central role in the
      innate immunity to H. pylori. However, epithelial receptors interacting with H.
      pylori have been poorly characterized so far. Recently a new triggering receptor
      expressed on myeloid cells-1 (TREM-1) has been identified on human neutrophils
      and monocytes. On these cells TREM-1 triggers innate immunity by stimulating the
      secretion of interleukin (IL)-8 and tumour necrosis factor (TNF)-alpha and thus
      amplifies bacterial-induced inflammation. In this study expression and function
      of TREM-1 in gastric epithelium exposed to H. pylori has been investigated. TREM
      1 mRNA and protein were expressed on gastric epithelial cell lines as
      demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) and
      fluorescence activated cell sorter analysis. Gastric epithelial TREM-1 expression
      was up-regulated directly by H. pylori and was independent of epithelial IL-8
      induced by H. pylori. Immunohistochemistry and tissue RT-PCR demonstrated
      significantly stronger TREM-1 expression in H. pylori gastritis compared with the
      non-inflamed gastric mucosa supporting in vivo that epithelial TREM-1 is up
      regulated during H. pylori infection. Stimulation of gastric epithelial TREM-1
      receptor resulted in IL-8 up-regulation on mRNA and protein level, as shown by
      real-time PCR and immunoassay. This is the first study localizing TREM-1 on
      gastric epithelium. Functional data suggest that TREM-1 expressed on gastric
      epithelium amplifies inflammation of the underlying gastric mucosa by up
      regulation of IL-8.

PMID- 18321352
TI  - EEG and psychiatry: time for a resurrection.

PMID- 18321353
TI  - Evaluation of clinical prognostic models for suicide attempts after a major
      depressive episode.
AB  - OBJECTIVE: In this study, we compare the performance of prognostic models of
      increasing complexity for prediction of future suicide attempt. METHOD: Using
      data from a 2-year prospective study of 304 depressed subjects, a series of Cox
      proportional hazard regression models were developed to predict future suicide
      attempt. The models were evaluated in terms of discrimination (the ability to
      rank subjects in order of risk), calibration (accuracy of predicted probabilities
      of attempt), and sensitivity and specificity of risk group stratification based
      on cross-validated predicted probabilities. RESULTS: Although an additive model
      with past attempt, smoking status, and suicidal ideation achieved 75% (cross
      validated) sensitivity and specificity, models that performed best in terms of
      discrimination included interactions between predictor variables. CONCLUSION: As
      several models had similar predictive power, clinical considerations and ease of
      interpretation may have a significant role in the final stage of model selection
      for assessing future suicide attempt risk.

PMID- 18321354
TI  - Maternal anxiety predicts favourable treatment outcomes in anxiety-disordered
      adolescents.
AB  - OBJECTIVE: To determine the differential impact of maternal and paternal
      internalizing psychopathology on cognitive-behavioural treatment (CBT) outcome of
      anxiety-disordered children and adolescents. METHOD: Participants consisted of
      127 children and 51 adolescents with a primary anxiety diagnosis. Children were
      randomly assigned to a standardized group CBT or individual CBT; adolescents
      received individual CBT. Parents received four training sessions. Participants
      were evaluated at pre- and post-treatment with a clinical interview and with self
      and parent-reported questionnaires. Lifetime anxiety and mood disorders in
      parents were obtained with a clinical interview. RESULTS: For children, no
      associations were found between maternal and paternal anxiety or mood disorders
      and treatment outcome. For adolescents, however, maternal lifetime anxiety
      disorders were positively associated with pre-post-treatment improvement in
      clinician severity ratings and with treatment success. CONCLUSION: Lifetime
      maternal anxiety disorders were significantly associated with favourable
      treatment outcomes in adolescents. Paternal disorders were not associated with
      treatment response.

PMID- 18321355
TI  - Fetal growth restriction and the development of major depression.
AB  - OBJECTIVE: To test the association between fetal growth restriction and the
      lifetime risk of major depression and the number of recurrent episodes. METHOD:
      Study subjects (n = 1101) were offspring of participants in the Providence, RI,
      site of the National Collaborative Perinatal Project. Cox regression was used to
      investigate the relation between measures of birth size and the lifetime risk of
      depression and the mean number of depressive episodes was compared across
      categories of birth size. RESULTS: There was no association between low birth
      weight, gestational age, ponderal index and small for gestational age and the
      lifetime risk of major depression, or the number of recurrent episodes.
      CONCLUSION: Fetal growth restriction, as reflected by multiple measures of birth
      size, is not associated with the risk of a major depression or the subsequent
      recurrence of depressive episodes. Results of this study do not support a 'fetal
      programming' effect in depression.

PMID- 18321358
TI  - Dr. Folkman's legacy-a life of angiogenesis research.

PMID- 18321359
TI  - MUC-1 mucin in normal human salivary glands detected by HMFG-1 and HMFG-2
      monoclonal antibodies.
AB  - The aim of this study was to determine the immunoexpression of normal salivary
      gland cells using two human milk fat globule membrane protein antibodies (HMFG-1
      and HMFG-2). Paraffin-embedded, 5 microm-thick slides from parotid and
      submandibular gland tissues were cut and immunostained with monoclonal antibodies
      HMFG-1 and HMFG-2 against MUC1 protein. HMFG antigens were found in secretory
      epithelial cells and ductal cells lining the striated and intercalated ducts in
      the intraductal secretion material, and sometimes in the myoepithelial cells. Our
      results suggest that HMFG-1 and HMFG-2 proteins may play a role in normal
      salivary gland function, mainly in the manufacturing and secretion of saliva.

PMID- 18321360
TI  - High frequency of gastroduodenal cytomegalovirus infection in liver transplant
      patients.
AB  - The prevalence and significance of cytomegalovirus (CMV) detected in biopsy
      specimens from the gastroduodenal mucosa of liver transplant patients, patients
      with chronic or acute liver failure and immunocompetent patients with dyspeptic
      symptoms were evaluated. 80 liver transplant patients with upper gastrointestinal
      symptoms, 132 patients with chronic and 25 with acute liver failure, and 33
      immunocompetent, dyspeptic patients underwent oesophagogastroduodenoscopies, with
      biopsies from the duodenum and stomach. CMV was demonstrated by
      immunohistochemistry in frozen sections, using a monoclonal antibody against CMV
      specific antigens (pp65 matrix protein), and in paraffin sections by a monoclonal
      antibody against delayed early protein (p52). 71% of the liver transplant
      patients, 45% of the patients with chronic liver disease, 20% with acute liver
      failure, and 45% of the immunocompetent, dyspeptic patients had CMV-positive
      findings in the gastroduodenal mucosa (liver transplant patients vs other groups,
      p<0.01). Histopathological findings in CMV-positive samples were focal
      inflammation, including increased inflammation of the lamina propria,
      infiltrating leukocytes intra-epithelially, regenerative changes in the
      epithelial cells and inclusion bodies. In conclusion, CMV-positive cells and
      inclusions are often found in the gastroduodenal mucosa of liver transplant
      patients, as well as in patients suffering from chronic liver disease or even in
      otherwise healthy patients with dyspeptic symptoms.

PMID- 18321361
TI  - Angiogenesis and expression of angiogenic agents in uterine and ovarian
      carcinosarcomas.
AB  - Carcinosarcomas of the female genital tract are a heterogeneous group of
      aggressive malignant neoplasms characterized by poor prognosis that contain
      elements expressing both carcinomatous and sarcomatous characteristics. In this
      study specimens from 25 patients were treated with labeled antibodies to vascular
      endothelium (FVIII), and to vascular endothelial growth factor (VEGF) for
      analysis of angiogenesis, and to vascular endothelial growth factor receptor 3
      (VEGFR-3) for analysis of lymphangiogenesis, in 11,099 vessels. Automated
      quantitative image analysis was used and the results were compared with clinical
      data. Microvessel density increased from a median value of 18.32 vessels/mm(2) in
      non-neoplastic stroma to 131.25 vessels/mm(2) in neoplasms. In areas around tumor
      islets expressing predominantly epithelial carcinomatous characteristics,
      microvessel density was increased three-fold compared with the islets themselves.
      Vessels were arranged in a garland-type pattern, or in bursts, and they exhibited
      directional angiogenesis. Clinical indicators of poor survival were high tumor
      stage (p=0.002) and age above 65 (p=0.0769). A high number of small vessels (16
      300 mum(2) in cross-sectional area) predicted poor survival (p=0.0149), and more
      so in tumors exhibiting predominantly sarcomatous characteristics (p=0.0087).
      Tumor tissue area above the median exhibiting VEGF expression was also a sign of
      poor survival (p=0.0267), as was an area of positive staining for VEGFR-3
      exceeding the median (p=0.00487). In this study, active angiogenesis (increased
      number of vessels, variable in shape and exhibiting decreased antibody staining
      intensity) was a distinct feature of carcinosarcomas, its extent and distribution
      depending upon neoplasm morphology. Increased vessel numbers and increased VEGF
      and VEGFR-3 expression indicated poor survival.

PMID- 18321362
TI  - The prevalence of ESBL-producing E. coli and Klebsiella strains in the Copenhagen
      area of Denmark.
AB  - The main purpose of the study was to investigate the frequency of ESBL-producing
      E. coli and Klebsiella strains in the Greater Copenhagen area. Four collections
      of strains were investigated: A) 380 consecutive E. coli and Klebsiella isolates
      primarily from urine, B) 200 gentamicin-resistant E. coli and Klebsiella isolates
      primarily from urine, C) 210 consecutive E. coli isolates from blood cultures,
      and D) 68 cefuroxime-resistant E. coli and Klebsiella isolates primarily from
      urine. Only one strain per patient was included. Strains with a zone diameter for
      cefpodoxime <or=23 mm were tested by a phenotypic confirmatory test for ESBL
      production and all screening test-positive strains were examined with PCR and
      nucleotide sequencing in order to detect the following ESBL genes: ctx-m, shv,
      tem and oxa. Strains resistant to cefoxitin were further examined with
      cefotetan+/-boronic acid in order to detect AmpC. An ESBL gene was detected in
      3/3 confirmatory test-positive isolates from collection A, in 14/17 from
      collection B, and in 41/48 from collection D. The distribution of isolates with
      the ESBL and/or AmpC enzymes was as follows: CTX-M (n=41), SHV (n=14), AmpC
      (n=9), CTX-M and AmpC (n=2), SHV and AmpC (n=1). In conclusion, the frequency of
      ESBL-producing E. coli and Klebsiella isolates was low in the Copenhagen area of
      Denmark (0.8 %). The most common ESBL genes found in our study were ctx-m and shv
      genes.

PMID- 18321363
TI  - Molecular profile and genetic diversity of cytolethal distending toxin (CDT)
      producing Escherichia coli isolates from diarrheal patients.
AB  - Cytolethal distending toxin (CDT)-producing Escherichia coli strains are
      considered to be a heterogeneous group of E. coli. In the present investigation,
      20 CDT-producing E. coli strains, which had already been shown to be cytotoxic
      necrotizing factor (cnf) gene positive, were selected by PCR. Since these strains
      proved to be CDT producers on CHO cells but were partially characterized by PCR,
      they were subjected to PCR analysis to amplify the complete coding region of cdt
      genes. Moreover, the genetic relatedness of these strains was examined by pulse
      field gel electrophoresis (PFGE). To check the extent of homogeneity of these
      strains at the chromosomal level, tRNA insertion site analysis was performed. The
      CDT-producing E. coli strains under investigation were shown to be heterogeneous
      and diverse in regard to their genetic analysis. This observed diversity could be
      an independent acquisition of virulence genes that might occur through horizontal
      gene transfer by mobile genetic elements. This conclusion is based on the fact
      that data shown by tRNA insertion site analysis revealed that there is no common
      pattern of insertion among these isolates although they do share a common trait
      of CDT production.

PMID- 18321364
TI  - Comparison of microscopy, culture and in-house PCR and NASBA assays for diagnosis
      of Neisseria gonorrhoeae in Russia.
AB  - This study aimed to assess the laboratory diagnosis of Neisseria gonorrhoeae in
      St. Petersburg, Russia. In total, 334 consecutive symptomatic patients were
      enrolled. Cervical and urethral specimens from women (n=286) and urethral
      specimens from men (n=48) were analyzed by microscopy, culture and two in-house
      NAATs, i.e. polymerase chain reaction (PCR) and nucleic acid sequence-based
      amplification (NASBA), developed in Russia. All N. gonorrhoeae-positive samples
      were confirmed using porA pseudogene and 16S rRNA gene sequencing. All methods
      displayed 100% specificity, i.e. positive predictive values of 100%. Compared to
      the PCR (most sensitive method in the present study), in women the sensitivity of
      both microscopy and culture was 31.8%, and that of NASBA was 90.9%. In men,
      microscopy, culture and NASBA displayed a sensitivity of 75%, 50% and 100%,
      respectively. The negative predictive values of microscopy, culture, and NASBA
      were 97.3%, 97.3%, and 99.6% in women, and 97.8%, 95.7%, and 100% in men,
      respectively. According to the PCR, the prevalences of N. gonorrhoeae were 4.5%
      (women) and 8.3% (men). In conclusion, both the investigated Russian NAATs
      displayed a high sensitivity and specificity. However, in general the diagnosis
      of gonorrhoea in Russia is suboptimal and crucially requires validation,
      improvements and quality assurance.

PMID- 18321365
TI  - Pagetoid dyskeratosis of the nipple epidermis: an incidental finding mimicking
      Paget's disease of the nipple.
AB  - Pagetoid dyskeratosis (PD) is considered a selective keratinocytic response in
      which a small part of the normal population of pale keratinocytes is induced to
      proliferate. PD has been found incidentally in the squamous epithelium of the
      skin and mucosas in various locations, but not in the nipple. In cases in which
      PD cells are conspicuous, there is the danger of overdiagnosis. In a
      retrospective study, we describe the location and incidence of PD and other pale
      cells in the nipple epidermis, in 288 mastectomy specimens from women operated on
      for breast carcinoma, in situ or infiltrating, selected consecutively from our
      histopathologic files. In addition to the conventional histologic methods an
      immunohistochemical study was performed in selected cases. PD was found in 184
      (63.9%) cases and was a prominent finding in 37 (12.8%) cases. Toker cells (TCs)
      were identified by standard light microscopy in 24 (8.3%) nipples. Paget
      carcinoma cells (PCCs) were found in 12 (4.2%) cases, and in 9 (3.1%) they were
      an incidental finding. The immunohistochemical profile of each type of pale cells
      was as follows: PD cells, EMA-,LMWCK-,CK7-,HMWCK+, CEA-, HER2/neu protein-, HMB45
      , HPV-; TCs, EMA+, LMWCK+, CK7+, HMWCK-, CEA-, HER2/neu protein-, HMB45-, HPV-;
      PCCs, EMA+, LMWCK+, CK7+, HMWCK-, CEA+, HER2/neu protein+, HMB45-, HPV-. In
      conclusion, friction may be the stimulus for the appearance of PD cells. PD cells
      must be distinguished from TCs, PCCs, clear cells of Bowen's disease, pagetoid
      melanoma cells, cells of clear cell papulosis, koilocytes, artifactual clear
      cells, and glycogen-rich squamous cells. A combination of immunohistochemical
      markers is useful for this distinction; however, routine histologic study is
      usually adequate for recognizing PD. Pathologists should be familiar with the
      histologic features of PD in the nipple epidermis to avoid misdiagnosis.

PMID- 18321366
TI  - Magnitude of bacteraemia is associated with increased mortality in non-typhoid
      salmonellosis: a one-year follow-up study.
AB  - We examined whether the number of positive bottles in a routinely used three
      bottle blood culture (BC) set predicted one-year mortality in adult patients with
      non-typhoid Salmonella (NTS). Data from 1994 through 2003 in North Jutland
      County, Denmark, were retrieved from health databases and medical records. We
      used the number of positive BC bottles as an index of magnitude of NTS
      bacteraemia: Index 0 (reference) patients had a negative BC coincident with an
      NTS-positive faecal culture and index 1, 2, or 3 patients had increasing levels
      of NTS bacteraemia. For all patients and for patients with gastroenteritis we
      computed Kaplan-Meier curves to summarize survival over time and Cox regression
      analysis to estimate mortality in crude analyses and in analyses adjusted for
      comorbidity and age. There were 115, 43, 21, and 41 patients with index 0, 1, 2,
      and 3, respectively. One-year cumulative mortality was 4.4%, 14.0%, 28.6%, and
      41.5% for indices 0 to 3. Adjusted one-year mortality rate ratios (with 95%
      confidence intervals) were 1.7 (0.5-5.8), 5.2 (1.5-17.4), and 5.3 (1.9-14.9) for
      index 1, 2, and 3 patients, respectively. These estimates remained robust for
      patients with gastroenteritis. We conclude that higher magnitude of bacteraemia
      predicted one-year mortality in NTS patients.

PMID- 18321367
TI  - Absence of COSMC gene mutations in breast and colorectal carcinomas.

PMID- 18321368
TI  - Scoring vaginal fluid smears for diagnosis of bacterial vaginosis: need for
      quality specifications.

PMID- 18321369
TI  - Exaggerated placental site lesion with unusual presentation in the cervix of a
      perimenopausal patient.

PMID- 18321370
TI  - Acute megakaryoblastic leukemia mimicking small round cell tumor with novel
      t(1;5)(q21;p13).
AB  - Acute megakaryoblastic leukemia is a relatively rare form of acute leukemia that
      has heterogeneous blast morphology and karyotypic abnormalities. An 8-month-old
      boy with a retroperitoneal mass was diagnosed as having acute megakaryoblastic
      leukemia that initially presented as small round cell tumor of childhood. Bone
      marrow aspiration showed syncytial groups of atypical medium sized cells with
      scant cytoplasm and fine nuclear chromatin. Retroperitoneal mass biopsy showed
      several lymph nodes with cohesive clusters of neoplastic cells that demonstrated
      expression of Factor VIII. Flow cytometric analysis of the second bone marrow
      aspiration showed CD 61 positivity. Karyotypic analysis of bone marrow cells
      showed a novel translocation, (1;5)(q21;p13).

PMID- 18321371
TI  - Plasma cell granuloma of the thyroid.
AB  - We report two cases of thyroidal plasma cell granuloma. Both patients underwent
      surgical resection after presenting with painless neck swelling. Histopathologic
      examination of the specimens revealed plasmacytes infiltrating the thyroid
      parenchyma and immunohistochemical studies showed the polyclonal nature of the
      plasma cells. Plasma cell granuloma is a benign lesion and its appearance in the
      thyroid gland is extremely rare. Eleven prior cases with thyroid localization
      have been reported to date in the English literature. Nine of the plasma cell
      granuloma cases occurred in women, four in men (including the present cases). The
      clinicopathologic features and diagnostic difficulties of this rare entity are
      described, and its relation to inflammatory pseudotumor of other sites is
      discussed with a review of the literature.

PMID- 18321372
TI  - Influence of two different resection techniques (conventional liver resection
      versus anterior approach) of liver metastases from colorectal cancer on
      hematogenous tumor cell dissemination - prospective randomized multicenter trial.
AB  - BACKGROUND: Surgical hepatic resection remains the treatment of choice for
      patients with liver metastases from colorectal cancer despite the use of
      alternative therapeutic strategies. Although this procedure provides long-term
      survival in a significant number of patients, 50-75% of the patients develop
      intra- and/or extrahepatic recurrence. One possible reason for tumor recurrence
      may be intraoperative hematogenous tumor cell dissemination due to mechanical
      manipulation of the tumor during hepatic resection. Surgical technique may have
      an influence on hematogenous tumor cell spread. We hypothesize that hematogenous
      tumor cell dissemination may be reduced by using the anterior approach technique
      compared to conventional liver resection. METHODS/DESIGN: This is a multi-centre
      prospective randomized controlled, superiority trial to compare two liver
      resection techniques of liver metastases from colorectal cancer. 150 patients
      will be included and randomized intraoperatively after surgical exploration just
      prior to resection. The primary objective is to compare the anterior approach
      with the conventional liver resection technique with regard to intraoperative
      haematogenous tumor cell dissemination. As secondary objectives we examine five
      year survival rates (OS and DFS), blood loss, duration of operation, requirement
      of blood transfusions, morbidity rate, prognostic relevance of tumor cell
      detection in blood and bone marrow and the comparison of tumor cell detection by
      different detection methods. CONCLUSION: This trial will answer the question
      whether there is an advantage for the anterior approach technique compared to the
      conventional resection group with regard to tumor cell dissemination. It will
      also add further information about prognostic differences, safety, advantages and
      disadvantages of each technique. TRIAL REGISTRATION: Current controlled trials -
      ISRCTN45066244.

PMID- 18321373
TI  - Clustering of cognate proteins among distinct proteomes derived from multiple
      links to a single seed sequence.
AB  - BACKGROUND: Modern proteomes evolved by modification of pre-existing ones. It is
      extremely important to comparative biology that related proteins be identified as
      members of the same cognate group, since a characterized putative homolog could
      be used to find clues about the function of uncharacterized proteins from the
      same group. Typically, databases of related proteins focus on those from
      completely-sequenced genomes. Unfortunately, relatively few organisms have had
      their genomes fully sequenced; accordingly, many proteins are ignored by the
      currently available databases of cognate proteins, despite the high amount of
      important genes that are functionally described only for these incomplete
      proteomes. RESULTS: We have developed a method to cluster cognate proteins from
      multiple organisms beginning with only one sequence, through connectivity
      saturation with that Seed sequence. We show that the generated clusters are in
      agreement with some other approaches based on full genome comparison. CONCLUSION:
      The method produced results that are as reliable as those produced by
      conventional clustering approaches. Generating clusters based only on individual
      proteins of interest is less time consuming than generating clusters for whole
      proteomes.

PMID- 18321374
TI  - Ethnopharmacological uses of Erythrina senegalensis: a comparison of three areas
      in Mali, and a link between traditional knowledge and modern biological science.
AB  - This paper describes ethnopharmacological knowledge on the uses of Erythrina
      senegalensis DC (Fabaceae) in traditional medicine in three different areas
      (Dioila, Kolokani and Koutiala) in Mali. Data were collected using interviews of
      traditional healers selected randomly. The main reported diseases for which E.
      senegalensis was used by the traditional healers were amenorrhea, malaria,
      jaundice, infections, abortion, wound, and body pain (chest pain, back pain,
      abdominal pain etc). The fidelity level (which estimates the agreement of
      traditional healers on the same area about a reported use of the plant) was
      calculated to compare the results from the three areas. Certain differences were
      noticed, the most striking was the fact that amenorrhea was the most reported
      disease in Dioila and Kolokani with 21% of agreement for both areas, while this
      use was not reported in Koutiala at all. Similarities existed between the three
      areas on the use of the plant against malaria and infections, although with
      different degree of agreement among the healers. We also report the results of a
      literature survey on compounds isolated from the plant and their biological
      activities. A comparison of these results with the ethnopharmacological
      information from Mali and other countries showed that some of the traditional
      indications in Mali are scientifically supported by the literature. For instance,
      the use of E. senegalensis against infectious diseases (bilharzias,
      schistosomiasis, pneumonia etc.) is sustained by several antibacterial and
      antifungal compounds isolated from different parts of the plant. The comparison
      also showed that pharmacologists have not fully investigated all the possible
      bioactivities that healers ascribe to this plant.

PMID- 18321375
TI  - An investigation into the prevalence of dog bites to primary school children in
      Trinidad.
AB  - BACKGROUND: To estimate the prevalence of dog bites to primary school children
      between the ages of 8-12 years using a semi-structured interview process. With
      the increase in the pet population and popularity of dangerous breeds of dog and
      a high stray dog population combined with a dearth of information on the risk of
      dog attacks to children in Trinidad, a semi-structured interview process was used
      to determine risk factors associated with dog attacks. METHODS: A questionnaire
      survey of 1109 primary school children between the ages of 8-12 years was
      conducted in Trinidad from November 2002 to September 2003. The survey was
      conducted to determine the risk factors such as age, gender, size of dog and
      relationship of dog and victim, in dog bite incidents. The chi-square statistic
      and odds ratios were used to estimate risk factors for a bite incident. RESULTS:
      Twenty-eight percent of children were bitten at least once by a dog. Gender
      (male) and owning a dog were statistically significant risk factors (p = 0.003
      and 0.008 respectively, chi2 df, 95% confidence). Most attacks occurred outside
      of the home (58.0%) followed by the victims' home (42.0%) and were by a dog known
      but not owned (54.6%) by the victim. Many victims (33.0%) were bitten without
      having any interaction with the dog and the majority (61.9%) of victims did not
      receive professional medical assistance. Overall, the lower leg or foot was most
      often injured (39.3%). CONCLUSION: A public educational campaign is needed on
      responsible pet ownership. In addition, children must be taught effective ways of
      avoiding attacks or reducing injury in the event of a dog attack. The Dangerous
      dogs Act 2000 must be proclaimed in parliament by the Government of Trinidad and
      Tobago to exert more pressure on pet owners to safeguard the public from the
      menace of dog attacks.

PMID- 18321376
TI  - Evolution of the hepcidin gene in primates.
AB  - BACKGROUND: Hepcidin/LEAP-1 is an iron regulatory hormone originally identified
      as an antimicrobial peptide. As part of a systematic analysis of the evolution of
      host defense peptides in primates, we have sequenced the orthologous gene from 14
      species of non-human primates. RESULTS: The sequence of the mature peptide is
      highly conserved amongst all the analyzed species, being identical to the human
      one in great apes and gibbons, with a single residue conservative variation in
      Old-World monkeys and with few substitutions in New-World monkeys. CONCLUSION:
      Our analysis indicates that hepcidin's role as a regulatory hormone, which
      involves interaction with a conserved receptor (ferroportin), may result in
      conservation over most of its sequence, with the exception of the stretch between
      residues 15 and 18, which in New-World monkeys (as well as in other mammals)
      shows a significant variation, possibly indicating that this structural region is
      involved in other functions.

PMID- 18321377
TI  - Should a colon cancer screening decision aid include the option of no testing? A
      comparative trial of two decision aids.
AB  - BACKGROUND: An important question in the development of decision aids about colon
      cancer (CRC) screening is whether to include an explicit discussion of the option
      of not being screened. We examined the effect of including or not including an
      explicit discussion of the option of deciding not to be screened in a CRC
      screening decision aid on subjective measures of decision aid content; interest
      in screening; and knowledge. METHODS: Adults ages 50-85 were assigned to view one
      of two versions of the decision aid. The two versions differed only in the
      inclusion of video segments of two men, one of whom decided against being
      screened. Participants completed questionnaires before and after viewing the
      decision aid to compare subjective measures of content, screening interest and
      intent, and knowledge between groups. Likert response categories (5-point) were
      used for subjective measures of content (eg. clarity, balance in favor/against
      screening, and overall rating), and screening interest. Knowledge was measured
      with a three item index and individual questions. Higher scores indicated
      favorable responses for subjective measures, greater interest, and better
      knowledge. For the subjective balance, lower numbers were associated with the
      impression of the decision aid favoring CRC screening. RESULTS: 57 viewed the
      "with" version which included the two segments and 49 viewed the "without"
      version. After viewing, participants found the "without" version to have better
      subjective clarity about benefits of screening ("with" 3.4, "without" 4.1, p <
      0.01), and to have greater clarity about downsides of screening ("with" 3.2,
      "without" 3.6, p = 0.03). The "with" version was considered to be less strongly
      balanced in favor of screening. ("with" 1.8, "without" 1.6, p = 0.05); but the
      "without" version received a better overall rating ("with" 3.5, "without" 3.8, p
      = 0.03). Groups did not differ in screening interest after viewing a decision aid
      or knowledge. CONCLUSION: A decision aid with the explicit discussion of the
      option of deciding not to be screened appears to increase the impression that the
      program was not as strongly in favor of screening, but decreases the impression
      of clarity and resulted in a lower overall rating. We did not observe clinically
      important or statistically significant differences in interest in screening or
      knowledge.

PMID- 18321379
TI  - CD 56 staining in liver biopsies does not help in differentiating extrahepatic
      biliary atresia from other causes of neonatal cholestasis.
AB  - INTRODUCTION: Several conditions are considered in differential diagnosis of
      neonatal cholestasis. Of these the most important is extrahepatic biliary atresia
      (EHBA), while prompt diagnosis and surgical correction of obstruction can
      ameliorate clinical symptoms, provides long term survival for about one fourth of
      patients and serves as an important bridge to transplantation for many others.
      From histopathologic standpoint, features of EHBA overlaps with other diagnoses
      and so ancillary tests such as immunohistochemical staining for CD56 is suggested
      by some authors as a helpful tool in differential diagnosis.Hereby we wanted to
      examine this staining in our center which is a referral children hospital and to
      prove its efficacy in our problematic cases. MATERIALS AND METHODS: By
      retrospective review of pathology records during 2000 to 2006 in Markaze Tebbi
      Koodakan (children hospital related to Tehran University of Medical Sciences), we
      selected 17 cases of EHBA as patients and 12 cases with other diagnoses as
      controls, both with some degree of bile ductular proliferation in liver biopsies.
      EHBA cases were all proved by surgery. Four of control cases also underwent
      surgery but proved to have open ducts by intra-operative cholangiography. Long
      term follow up and other tests ruled out EHBA in other 8 cases. Hematoxylin-Eosin
      stains of paraffin blocks were studied again and freshly prepared sections were
      immunostained for CD56. RESULTS: Bile ducts and proliferating bile ductules were
      strongly positive for CD56 in 6 of 17 cases of EHBA. In 7 out of 17, positivity
      were seen in more than two thirds of portal tracts. In controls, one case showed
      strong positivity and 6 out of twelve showed positivity in more than two thirds
      of portal tracts. The intensity and distribution of CD56 staining did not differ
      significantly between two groups. DISCUSSION: Despite findings of previous
      studies, we have shown that CD56 staining can not help as an ancillary test in
      differential diagnosis of neonatal cholestasis and perhaps other markers should
      be tested in this regard.

PMID- 18321378
TI  - Cross-kingdom patterns of alternative splicing and splice recognition.
AB  - BACKGROUND: Variations in transcript splicing can reveal how eukaryotes recognize
      intronic splice sites. Retained introns (RIs) commonly appear when the intron
      definition (ID) mechanism of splice site recognition inconsistently identifies
      intron-exon boundaries, and cassette exons (CEs) are often caused by variable
      recognition of splice junctions by the exon definition (ED) mechanism. We have
      performed a comprehensive survey of alternative splicing across 42 eukaryotes to
      gain insight into how spliceosomal introns are recognized. RESULTS: All
      eukaryotes we studied exhibit RIs, which appear more frequently than previously
      thought. CEs are also present in all kingdoms and most of the organisms in our
      analysis. We observe that the ratio of CEs to RIs varies substantially among
      kingdoms, while the ratio of competing 3' acceptor and competing 5' donor sites
      remains nearly constant. In addition, we find the ratio of CEs to RIs in each
      organism correlates with the length of its introns. In all 14 fungi we examined,
      as well as in most of the 9 protists, RIs far outnumber CEs. This differs from
      the trend seen in 13 multicellular animals, where CEs occur much more frequently
      than RIs. The six plants we analyzed exhibit intermediate proportions of CEs and
      RIs. CONCLUSION: Our results suggest that most extant eukaryotes are capable of
      recognizing splice sites via both ID and ED, although ED is most common in
      multicellular animals and ID predominates in fungi and most protists.

PMID- 18321380
TI  - Glycosyltransferase efficiently controls phenylpropanoid pathway.
AB  - BACKGROUND: In a previous study, anthocyanin levels in potato plants were
      increased by manipulating genes connected with the flavonoid biosynthesis
      pathway. However, starch content and tuber yield were dramatically reduced in the
      transgenic plants, which over-expressed dihydroflavonol reductase (DFR). RESULTS:
      Transgenic plants over-expressing dihydroflavonol reductase (DFR) were
      subsequently transformed with the cDNA coding for the glycosyltransferase (UGT)
      of Solanum sogarandinum in order to obtain plants with a high anthocyanin content
      without reducing tuber yield and quality. Based on enzyme studies, the
      recombinant UGT is a 7-O-glycosyltransferase whose natural substrates include
      both anthocyanidins and flavonols such as kaempferol and quercetin. In the super
      transformed plants, tuber production was much higher than in the original
      transgenic plants bearing only the transgene coding for DFR, and was almost the
      same as in the control plants. The anthocyanin level was lower than in the
      initial plants, but still higher than in the control plants. Unexpectedly, the
      super-transformed plants also produced large amounts of kaempferol, chlorogenic
      acid, isochlorogenic acid, sinapic acid and proanthocyanins. CONCLUSION: In
      plants over-expressing both the transgene for DFR and the transgene for UGT, the
      synthesis of phenolic acids was diverted away from the anthocyanin branch. This
      represents a novel approach to manipulating phenolic acids synthesis in plants.

PMID- 18321382
TI  - Post-traumatic stress disorder among people exposed to the Ventotene street
      disaster in Rome.
AB  - OBJECTIVE: To test five hypotheses on Post-traumatic stress disorder (PTSD): 1)
      Is PTSD the most prevalent disorder after trauma? 2) Is the proximity to the
      disaster related to the risk of PTSD? 3) Is PTSD associated with child mourning
      or separation, previous stress, or familiarity for psychiatric disorders? 4) Does
      the exposition to trauma increase substance abuse or somatization? 5) Can
      episodic trauma cause long-lasting psychiatric morbidity? METHODS: Clinical
      assessment of subjects exposed to an explosion in a building caused by a gas
      leak. Best estimate clinical diagnoses were made according to DSM-IV-TR criteria.
      The Zung Depression Rating Scale, the Zung Anxiety Rating Scale, and the
      Clinician Administered Post Traumatic Stress Disorder Scale were used in the
      clinical assessment. Statistical analysis was performed by means of t-test with
      Bonferroni's correction on continuous variables and chi2 or Fisher test on
      categorical variables. RESULTS: PTSD was the most prevalent disorder after
      trauma, diagnosed in 32 (36.8%) subjects. The subjects who had not seen dead or
      injured people were more likely to receive no psychiatric diagnosis. Civil
      status, parenthood, death of relatives in the disaster, personal injuries,
      history of child mourning or separation, of previous stress, as well as
      familiarity for any psychiatric disorder or substance use disorder were not
      related with the rate of ascertained psychiatric diagnoses. Nearly two years
      after trauma, most of patients who had suffered PTSD still met PTSD criteria.
      CONCLUSION: The 1st and the 5th hypotheses were corroborated, the 3rd and the 4th
      hypotheses were not confirmed. The 2nd hypothesis was partially confirmed.

PMID- 18321381
TI  - B-mode ultrasound common carotid artery intima-media thickness and external
      diameter: cross-sectional and longitudinal associations with carotid
      atherosclerosis in a large population sample.
AB  - BACKGROUND: Arterial diameter and intima-media thickness (IMT) enlargement may
      each be related to the atherosclerotic process. Their separate or combined
      enlargement may indicate different arterial phenotypes with different
      atherosclerosis risk. METHODS: We investigated cross-sectional (baseline 1987-89:
      n = 7956) and prospective (median follow-up = 5.9 years: n = 4845) associations
      between baseline right common carotid artery (RCCA) external diameter and IMT
      with existing and incident carotid atherosclerotic lesions detected by B-mode
      ultrasound in any right or left carotid segments. Logistic regression models
      (unadjusted, adjusted for IMT, or adjusted for IMT and risk factors) were used to
      relate baseline diameter to existing carotid lesions while comparably adjusted
      parametric survival models assessed baseline diameter associations with carotid
      atherosclerosis progression (incident carotid lesions). Four baseline arterial
      phenotypes were categorized as having 1) neither IMT nor diameter enlarged
      (reference), 2) isolated IMT thickening, 3) isolated diameter enlargement, and 4)
      enlargement of both IMT and diameter. The association between these phenotypes
      and progression to definitive carotid atherosclerotic lesions was assessed over
      the follow-up period. RESULTS: Each standard deviation increment of baseline RCCA
      diameter was associated with increasing carotid lesion prevalence (unadjusted
      odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.47-1.62) and with
      progression of carotid atherosclerosis (unadjusted hazards ratio (HR) = 1.37, 95%
      CI = 1.28-1.46); and the associations remained significant even after adjustment
      for IMT and risk factors (prevalence OR = 1.11, 95% CI = 1.04-1.18; progression
      HR = 1.11, 95% CI = 1.03-1.19). Controlling for gender, age and race, persons
      with both RCCA IMT and diameter in the upper 50th percentiles had the greatest
      risk of progressing to clearly defined carotid atherosclerotic lesions (all HR =
      1.71, 95% CI = 1.47-2.0; men HR = 1.88, 95% CI = 1.48-2.39; women HR = 1.59, 95%
      CI = 1.31-1.95) while RCCA IMT or diameter alone in the upper 50th percentile
      produced significantly lower estimated risks. CONCLUSION: RCCA IMT and external
      diameter provide partially overlapping information relating to carotid
      atherosclerotic lesions. More importantly, the RCCA phenotype of coexistent wall
      thickening with external diameter enlargement indicates higher atherosclerotic
      risk than isolated wall thickening or diameter enlargement.

PMID- 18321383
TI  - Concomitant sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman
      Disease) and diffuse large B-cell lymphoma: a case report.
AB  - INTRODUCTION: Sinus histiocytosis with massive lymphadenopathy, also known as
      Rosai-Dorfman Disease, is a rare and benign source of lymphadenopathy first
      described in 1969, which mimics neoplastic processes. This disease commonly
      presents in children and young adults with supra-diaphragmatic lymphadenopathy or
      extranodal lesions consisting of tissue infiltrates composed of a polyclonal
      population of histiocytes. Since its description greater than 400 cases have been
      described, sometimes in patients with a variety of treated and untreated
      neoplastic diseases. However, the literature contains reports of only 19 cases of
      Rosai-Dorfman Disease in association with lymphomas, Hodgkin's or non-Hodgkin's.
      The majority of these cases have the two diagnoses, malignant lymphoma and Rosai
      Dorfman Disease, separated in time. Interestingly, infradiaphragmatic
      lymphadenopathy was a feature in the majority of previously reported cases of
      Rosai-Dorfman Disease and non-Hodgkin's lymphoma. CASE PRESENTATION: This report
      provides details of a case with co-existing sinus histiocytosis with massive
      lymphadenopathy and diffuse large B cell non-Hodgkin's lymphoma. This case is the
      fifth described case of simultaneous Rosai-Dorfman Disease and concurrent non
      Hodgkin's lymphoma. Unfortunately, the diagnosis of a clinically aggressive
      diffuse large B cell lymphoma was made at autopsy. The aggressive biological
      behavior of the diffuse large B cell lymphoma in this patient may have been
      related to the underlying immune dysregulation believed to be part of the
      pathophysiology of Rosai-Dorfman Disease. CONCLUSION: Taken together this report
      and the preceding reports of Rosai-Dorfman Disease and non-Hodgkin's lymphoma
      suggests that in cases with a diagnosis of Rosai-Dorfman Disease in the setting
      of prominent infradiaphragmatic lymphadenopathy, clinicians should maintain a
      high index of suspicion for the presence of occult non-Hodgkin's lymphoma
      especially if the clinical course is atypical for classic Rosai-Dorfman Disease.

PMID- 18321384
TI  - Concentration and purification by magnetic separation of the erythrocytic stages
      of all human Plasmodium species.
AB  - BACKGROUND: Parasite concentration methods facilitate molecular, biochemical and
      immunological research on the erythrocytic stages of Plasmodium. In this paper,
      an adaptation of magnetic MACS(R) columns for the purification of human
      Plasmodium species is presented. This method was useful for the
      concentration/purification of either schizonts or gametocytes. RESULTS AND
      CONCLUSIONS: The magnetic removal of non-parasitized red blood cells (in vivo and
      in vitro) using magnetic columns (MACS) was evaluated. This easy-to-use technique
      enriched schizonts and gametocytes from Plasmodium falciparum in vitro cultures
      with a very high degree of purity. In addition, all haemozoin-containing stages
      (schizonts and/or gametocytes) from the peripheral blood of infected patients
      could be concentrated using this method. This method is particularly useful for
      the concentration of non-falciparum species, which do not grow in culture and are
      otherwise difficult to obtain in large amounts.

PMID- 18321385
TI  - The Innate Immune Database (IIDB).
AB  - BACKGROUND: As part of a National Institute of Allergy and Infectious Diseases
      funded collaborative project, we have performed over 150 microarray experiments
      measuring the response of C57/BL6 mouse bone marrow macrophages to toll-like
      receptor stimuli. These microarray expression profiles are available freely from
      our project web site http://www.innateImmunity-systemsbiology.org. Here, we
      report the development of a database of computationally predicted transcription
      factor binding sites and related genomic features for a set of over 2000 murine
      immune genes of interest. Our database, which includes microarray co-expression
      clusters and a host of web-based query, analysis and visualization facilities, is
      available freely via the internet. It provides a broad resource to the research
      community, and a stepping stone towards the delineation of the network of
      transcriptional regulatory interactions underlying the integrated response of
      macrophages to pathogens. DESCRIPTION: We constructed a database indexed on genes
      and annotations of the immediate surrounding genomic regions. To facilitate both
      gene-specific and systems biology oriented research, our database provides the
      means to analyze individual genes or an entire genomic locus. Although our focus
      to-date has been on mammalian toll-like receptor signaling pathways, our database
      structure is not limited to this subject, and is intended to be broadly
      applicable to immunology. By focusing on selected immune-active genes, we were
      able to perform computationally intensive expression and sequence analyses that
      would currently be prohibitive if applied to the entire genome. Using six
      complementary computational algorithms and methodologies, we identified
      transcription factor binding sites based on the Position Weight Matrices
      available in TRANSFAC. For one example transcription factor (ATF3) for which
      experimental data is available, over 50% of our predicted binding sites coincide
      with genome-wide chromatin immnuopreciptation (ChIP-chip) results. Our database
      can be interrogated via a web interface. Genomic annotations and binding site
      predictions can be automatically viewed with a customized version of the Argo
      genome browser. CONCLUSION: We present the Innate Immune Database (IIDB) as a
      community resource for immunologists interested in gene regulatory systems
      underlying innate responses to pathogens. The database website can be freely
      accessed at http://db.systemsbiology.net/IIDB.

PMID- 18321386
TI  - A group randomized trial of a complexity-based organizational intervention to
      improve risk factors for diabetes complications in primary care settings: study
      protocol.
AB  - BACKGROUND: Most patients with type 2 diabetes have suboptimal control of their
      glucose, blood pressure (BP), and lipids - three risk factors for diabetes
      complications. Although the chronic care model (CCM) provides a roadmap for
      improving these outcomes, developing theoretically sound implementation
      strategies that will work across diverse primary care settings has been
      challenging. One explanation for this difficulty may be that most strategies do
      not account for the complex adaptive system (CAS) characteristics of the primary
      care setting. A CAS is comprised of individuals who can learn, interconnect, self
      organize, and interact with their environment in a way that demonstrates non
      linear dynamic behavior. One implementation strategy that may be used to leverage
      these properties is practice facilitation (PF). PF creates time for learning and
      reflection by members of the team in each clinic, improves their communication,
      and promotes an individualized approach to implement a strategy to improve
      patient outcomes. SPECIFIC OBJECTIVES: The specific objectives of this protocol
      are to: evaluate the effectiveness and sustainability of PF to improve risk
      factor control in patients with type 2 diabetes across a variety of primary care
      settings; assess the implementation of the CCM in response to the intervention;
      examine the relationship between communication within the practice team and the
      implementation of the CCM; and determine the cost of the intervention both from
      the perspective of the organization conducting the PF intervention and from the
      perspective of the primary care practice. INTERVENTION: The study will be a group
      randomized trial conducted in 40 primary care clinics. Data will be collected on
      all clinics, with 60 patients in each clinic, using a multi-method assessment
      process at baseline, 12, and 24 months. The intervention, PF, will consist of a
      series of practice improvement team meetings led by trained facilitators over 12
      months. Primary hypotheses will be tested with 12-month outcome data.
      Sustainability of the intervention will be tested using 24 month data. Insights
      gained will be included in a delayed intervention conducted in control practices
      and evaluated in a pre-post design. PRIMARY AND SECONDARY OUTCOMES: To test
      hypotheses, the unit of randomization will be the clinic. The unit of analysis
      will be the repeated measure of each risk factor for each patient, nested within
      the clinic. The repeated measure of glycosylated hemoglobin A1c will be the
      primary outcome, with BP and Low Density Lipoprotein (LDL) cholesterol as
      secondary outcomes. To study change in risk factor level, a hierarchical or
      random effect model will be used to account for the nesting of repeated
      measurement of risk factor within patients and patients within clinics.

PMID- 18321388
TI  - Allergic hemiglossitis as a unique case of food allergy: a case report.
AB  - INTRODUCTION: A unique case of topical food allergy is presented with unilateral
      swelling of the tongue with ulceration. Only one similar case has been reported
      in 1972. CASE PRESENTATION: 76 years old female patient presented at the
      Emergency Department with a unilateral painful swelling and ulcerations of the
      tongue after eating mint chocolate. However the swelling did not compromised the
      airways the presentation was rather frightening for the patient. The allergic
      reaction responded to the parenteral steroid and oral chlorphenamine treatment
      and the three month follow up only revealed minimal scar formations. CONCLUSION:
      Unilateral hemiglossitis is a rare form of allergic reactions which is usually
      self-limiting with full recovery of which takes an unusually long time.

PMID- 18321387
TI  - Vaccinia virus lacking the deoxyuridine triphosphatase gene (F2L) replicates well
      in vitro and in vivo, but is hypersensitive to the antiviral drug (N)
      methanocarbathymidine.
AB  - BACKGROUND: The vaccinia virus (VV) F2L gene encodes a functional deoxyuridine
      triphosphatase (dUTPase) that catalyzes the conversion of dUTP to dUMP and is
      thought to minimize the incorporation of deoxyuridine residues into the viral
      genome. Previous studies with with a complex, multigene deletion in this virus
      suggested that the gene was not required for viral replication, but the impact of
      deleting this gene alone has not been determined in vitro or in vivo. Although
      the crystal structure for this enzyme has been determined, its potential as a
      target for antiviral therapy is unclear. RESULTS: The F2L gene was replaced with
      GFP in the WR strain of VV to assess its effect on viral replication. The
      resulting virus replicated well in cell culture and its replication kinetics were
      almost indistinguishable from those of the wt virus and attained similar titers.
      The virus also appeared to be as pathogenic as the WR strain suggesting that it
      also replicated well in mice. Cells infected with the dUTPase mutant would be
      predicted to affect pyrimidine deoxynucleotide pools and might be expected to
      exhibit altered susceptibility to pyrimidine analogs. The antiviral activity of
      cidofovir and four thymidine analogs were evaluated both in the mutant and the
      parent strain of this virus. The dUTPase knockout remained fully susceptible to
      cidofovir and idoxuridine, but was hypersensitive to the drug (N)
      methanocarbathymidine, suggesting that pyrimidine metabolism was altered in cells
      infected with the mutant virus. The absence of dUTPase should reduce cellular
      dUMP pools and may result in a reduced conversion to dTMP by thymidylate
      synthetase or an increased reliance on the salvage of thymidine by the viral
      thymidine kinase. CONCLUSION: We confirmed that F2L was not required for
      replication in cell culture and determined that it does not play a significant
      role on virulence of the virus in intranasally infected mice. The recombinant
      virus is hypersensitive to (N)-methanocarbathymidine and may reflect metabolic
      differences in the mutant virus.

PMID- 18321389
TI  - Dysfunctional interferon-alpha production by peripheral plasmacytoid dendritic
      cells upon Toll-like receptor-9 stimulation in patients with systemic lupus
      erythematosus.
AB  - BACKGROUND: It is well known that interferon (IFN)-alpha is important to the
      pathogenesis of systemic lupus erythematosus (SLE). However, several reports have
      indicated that the number of IFN-alpha producing cells are decreased or that
      their function is defective in patients with SLE. We studied the function of
      plasmacytoid dendritic cells (pDCs) under persistent stimulation of Toll-like
      receptor (TLR)9 via a TLR9 ligand (CpG ODN2216) or SLE serum. METHODS: The
      concentrations of IFN-alpha were determined in serum and culture supernatant of
      peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls
      after stimulation with CpG ODN2216 or SLE serum. The numbers of circulating pDCs
      were analyzed by fluoresence-activated cell sorting analysis. pDCs were treated
      with CpG ODN2216 and SLE serum repeatedly, and levels of produced IFN-alpha were
      measured. The expression of IFN-alpha signature genes and inhibitory molecules of
      TLR signaling were examined in PBMCs from SLE patients and healthy control
      individuals. RESULTS: Although there was no significant difference in serum
      concentration of IFN-alpha and number of circulating pDCs between SLE patients
      and healthy control individuals, the IFN-alpha producing capacity of PBMCs was
      significantly reduced in SLE patients. Interestingly, the degree which TLR9
      ligand-induced IFN-alpha production in SLE PBMCs was inversely correlated with
      the SLE serum-induced production of IFN-alpha in healthy PMBCs. Because repeated
      stimulation pDCs with TLR9 ligands showed decreased level of IFN-alpha
      production, continuous TLR9 stimulation may lead to decreased production of IFN
      alpha in SLE PBMCs. In addition, PBMCs isolated from SLE patients exhibited
      higher expression of IFN-alpha signature genes and inhibitory molecules of TLR
      signaling, indicating that these cells had already undergone IFN-alpha
      stimulation and had become desensitized to TLR signaling. CONCLUSION: We suggest
      that the persistent presence of endogenous IFN-alpha inducing factors induces TLR
      tolerance in pDCs of SLE patients, leading to impaired production of IFN-alpha.

PMID- 18321390
TI  - A new approach for the large-scale generation of mature dendritic cells from
      adherent PBMC using roller bottle technology.
AB  - BACKGROUND: Human monocyte-derived DC (mDC) loaded with peptides, protein, tumor
      cell lysates, or tumor cell RNA, are being tested as vaccines against multiple
      human malignancies and viral infection with great promise. One of the factors
      that has limited more widespread use of these vaccines is the need to generate
      mDC in large scale. Current methods for the large-scale cultivation of mDC in
      static culture vessels are labor- and time- intensive, and also require many
      culture vessels. Here, we describe a new method for the large-scale generation of
      human mDC from human PBMC from leukopheresis or buffy coat products using roller
      bottles, never attempted before for mDC generation. We have tested this
      technology using 850 cm2 roller bottles compared to conventional T-175 flat
      bottom static culture flasks. METHODS: DC were generated from adherent human PBMC
      from buffy coats or leukopherisis products using GM-CSF and IL-4 in T-175 static
      flasks or 850 cm2 roller bottles. The cells were matured over two days, harvested
      and analyzed for cell yield and mature DC phenotype by flow cytometry, and then
      functionally analyzed for their ability to activate allogeneic T-cell or recall
      antigen peptide-specific T-cell responses. RESULTS: Monocytes were found to
      adhere inside roller bottles to the same extent as in static culture flasks. The
      phenotype and function of the mDC harvested after maturation from both type of
      culture systems were similar. The yield of mDC from input PBMC in the roller
      bottle system was similar as in the static flask system. However, each 850 cm2
      roller bottle could be seeded with 4-5 times more input PBMC and could yield 4-5
      times as many mDC per culture vessel than the static flasks as a result.
      CONCLUSION: Our results indicate that the roller bottle technology can generate
      similar numbers of mDC from adherent PBMC as traditional static flask methods,
      but with having to use fewer culture vessels. Thus, this may be a more practical
      method to generate mDC in large-scale cutting down on the amount of laboratory
      manipulations, and can save both time and labor costs.

PMID- 18321391
TI  - Analysis of four achaete-scute homologs in Bombyx mori reveals new viewpoints of
      the evolution and functions of this gene family.
AB  - BACKGROUND: achaete-scute complexe (AS-C) has been widely studied at genetic,
      developmental and evolutional levels. Genes of this family encode proteins
      containing a highly conserved bHLH domain, which take part in the regulation of
      the development of central nervous system and peripheral nervous system. Many AS
      C homologs have been isolated from various vertebrates and invertebrates. Also,
      AS-C genes are duplicated during the evolution of Diptera. Functions besides
      neural development controlling have also been found in Drosophila AS-C genes.
      RESULTS: We cloned four achaete-scute homologs (ASH) from the lepidopteran model
      organism Bombyx mori, including three proneural genes and one neural precursor
      gene. Proteins encoded by them contained the characteristic bHLH domain and the
      three proneural ones were also found to have the C-terminal conserved motif.
      These genes regulated promoter activity through the Class A E-boxes in vitro.
      Though both Bm-ASH and Drosophila AS-C have four members, they are not in one by
      one corresponding relationships. Results of RT-PCR and real-time PCR showed that
      Bm-ASH genes were expressed in different larval tissues, and had well-regulated
      expressional profiles during the development of embryo and wing/wing disc.
      CONCLUSION: There are four achaete-scute homologs in Bombyx mori, the second
      insect having four AS-C genes so far, and these genes have multiple functions in
      silkworm life cycle. AS-C gene duplication in insects occurs after or parallel
      to, but not before the taxonomic order formation during evolution.

PMID- 18321392
TI  - Application of magnetic motor stimulation for measuring conduction time across
      the lower part of the brachial plexus.
AB  - OBJECTIVE: The objective of this study was to calculate central motor conduction
      time (CMCT) of median and ulnar nerves in normal volunteers. Conduction time
      across the lower part of the brachial plexus was measured by using magnetic
      stimulation over the motor cortex and brachial plexus and recording the evoked
      response in hand muscles. DESIGN: This descriptive study was done on 112 upper
      limbs of healthy volunteers. Forty-six limbs belonging to men and sixty-six
      belonging to women were studied by magnetic stimulation of both motor cortex and
      brachial plexus and recording the evoked response in thenar and hypothenar
      muscles. Stimulation of the motor cortex gives rise to absolute latency of each
      nerve whereas stimulation of the brachial plexus results in peripheral conduction
      time. The difference between these two values was considered the central motor
      conduction time (CMCT). RESULTS: In summary the result are as follows; Cortex
      thenar latency = 21.4 ms (SD = 1.7), CMCT-thenar = 9.6 ms (SD = 1.9), Cortex
      hypothenar latency = 21.3 ms (SD = 1.8), CMCT-hypothenar = 9.4 ms (SD = 1.8).
      CONCLUSION: These findings showed that there is no meaningful difference between
      two genders. CMCT calculated by this method is a little longer than that obtained
      by electrical stimulation that is due to the more distally placed second
      stimulation. We recommend magnetic stimulation as the method of choice to
      calculate CMCT and its use for lower brachial plexus conduction time. This method
      could serve as a diagnostic tool for diagnosis of lower plexus entrapment and
      injuries especially in early stages.

PMID- 18321393
TI  - Performance of Interleukin-6 and Interleukin-8 serum levels in pediatric oncology
      patients with neutropenia and fever for the assessment of low-risk.
AB  - BACKGROUND: Patients with chemotherapy-related neutropenia and fever are usually
      hospitalized and treated on empirical intravenous broad-spectrum antibiotic
      regimens. Early diagnosis of sepsis in children with febrile neutropenia remains
      difficult due to non-specific clinical and laboratory signs of infection. We
      aimed to analyze whether IL-6 and IL-8 could define a group of patients at low
      risk of septicemia. METHODS: A prospective study was performed to assess the
      potential value of IL-6, IL-8 and C-reactive protein serum levels to predict
      severe bacterial infection or bacteremia in febrile neutropenic children with
      cancer during chemotherapy. Statistical test used: Friedman test, Wilcoxon-Test,
      Kruskal-Wallis H test, Mann-Whitney U-Test and Receiver Operating
      Characteristics. RESULTS: The analysis of cytokine levels measured at the onset
      of fever indicated that IL-6 and IL-8 are useful to define a possible group of
      patients with low risk of sepsis. In predicting bacteremia or severe bacterial
      infection, IL-6 was the best predictor with the optimum IL-6 cut-off level of 42
      pg/ml showing a high sensitivity (90%) and specificity (85%). CONCLUSION: These
      findings may have clinical implications for risk-based antimicrobial treatment
      strategies.

PMID- 18321394
TI  - Self-reported competence, attitude and approach of physicians towards patients
      with dementia in ambulatory care: results of a postal survey.
AB  - BACKGROUND: Caring for patients with dementia is a demanding task. Little is
      known as to whether physicians feel competent enough to perform this task or
      whether a lack of self-perceived competence influences attitudes and professional
      approach. Even less is known with respect to potential differences between
      general practitioners (GPs) and specialists. The purpose of this study was to
      investigate the interrelationship between the self-perceived competence, attitude
      and professional approach of physicians in ambulatory care in Germany. A further
      aim was to compare GPs and specialists with regard to differences in these areas.
      METHODS: A standardised postal survey was sent to 389 GPs and 239 neurologists
      and psychiatrists in six metropolitan areas in Germany. The 49-item questionnaire
      consisted of attitudinal statements to be rated on a Likert-type scale. Return
      rates were 54 percent for GPs and 40 percent for specialists. Statistical methods
      used to analyze data included correlation analysis, cluster analysis and ordinal
      regression analysis. RESULTS: No differences were found between GPs and
      specialists with regard to their general attitude towards caring for patients
      with dementia. Approximately 15 percent of both disciplines showed a clearly
      negative attitude. Self-reported competence was strongly associated with general
      attitude. In particular among GPs, and less so among specialists, a strong
      positive association was found between self-reported competence, general attitude
      and professional approach (e.g. early detection, active case finding and
      cooperation with caregivers). Differences between GPs and specialists were
      smaller than expected and appear to predominantly reflect task differences within
      the German health care system. CONCLUSION: Training opportunities which enable in
      particular GPs to enhance not only their competence but also their general
      attitude towards dementia care would appear to be beneficial and might carry
      positive consequences for patients and their caregivers.

PMID- 18321395
TI  - Momordica charantia (bitter melon) reduces plasma apolipoprotein B-100 and
      increases hepatic insulin receptor substrate and phosphoinositide-3 kinase
      interactions.
AB  - Aqueous extracts or juice from unripened fruit of Momordica charantia (bitter
      melon) has traditionally been used in the treatment of diabetes and its
      complications. Insulin resistance is characterized by significant down-regulation
      of hepatic insulin signalling as documented by attenuated phosphorylation of
      insulin receptor (IR), IR substrates 1 and 2, phosphoinositide-3 kinase, protein
      kinase B, and over-expression of phosphotyrosine phosphatase 1B. We recently
      demonstrated that bitter melon juice (BMJ) is a potent inhibitor of apoB
      secretion and TAG synthesis and secretion in human hepatoma cells, HepG2, that
      may be involved in plasma lipid- and VLDL-lowering effects observed in animal
      studies. The aim of this study was to evaluate the effects of BMJ on plasma apoB
      levels and hepatic insulin signalling cascade in mice fed high-fat diet (HFD).
      Female C57BL/6 mice (4-6 weeks old) were randomized into three groups receiving
      regular rodent chow, HFD and HFD+BMJ. The data indicate that BMJ not only
      improves glucose and insulin tolerance but also lowers plasma apoB-100 and apoB
      48 in HFD-fed mice as well as modulates the phosphorylation status of IR and its
      downstream signalling molecules. Investigating the biochemical and molecular
      mechanisms involved in amelioration of diabetic dyslipidaemia by BMJ may lead to
      identification of new molecular targets for dietary/alternative therapies.

PMID- 18321396
TI  - Molecular mechanisms and treatment of bone metastasis.
AB  - The metastasis of cancer cells to bone alters bone architecture and mineral
      homeostasis. As described by the 'seed and soil' hypothesis, bone represents a
      fertile ground for cancer cells to flourish. A 'vicious cycle' of reciprocal bone
      cancer cellular signals occurs with osteolytic (bone-resorbing) metastases, and a
      similar mechanism likely modulates osteoblastic (bone-forming) metastatic lesions
      as well. The development of targeted therapies either to block initial cancer
      cell chemotaxis, invasion and adhesion or to break the 'vicious cycle' is
      dependent on a more complete understanding of bone metastases. Although
      bisphosphonates delay progression of skeletal metastases, it is clear that more
      effective therapies are needed. Cancer-associated bone morbidity remains a major
      public health problem, and to improve therapy and prevention it is important to
      understand the pathophysiology of the effects of cancer on bone. This review
      details scientific advances in this area.

PMID- 18321397
TI  - Misbinding of color to form in afterimages.
AB  - Under dichoptic viewing conditions, rivalrous gratings that differ in both color
      and form can give the percept of the color from one eye in part of the form in
      the other eye. This study examined the afterimage following such misbinding of
      color to form. The first experiment established that afterimages of the misbound
      percept were seen. Two possible mechanisms for the misbound afterimage are (1)
      persisting retinal representations that are rivalrous and subsequently resolved
      to give misbinding, as during rivalrous viewing, and (2) a persisting response
      from a central neural representation of the misbound percept with the form from
      one eye and color from the other eye. The results support afterimage formation
      from a central representation of the misbound percept, not from resolution of
      rivalrous monocular representations.

PMID- 18321398
TI  - Binocular rivalry between identical retinal stimuli with an induced color
      difference.
AB  - An open question in color rivalry is whether alternation between two colors is
      caused by a difference in receptoral stimulation or a difference in the neural
      representation of color appearance. This question was examined with binocular
      rivalry between physically identical lights that differed in appearance due to
      chromatic induction. Perceptual alternation was measured between gratings of the
      same chromaticity; each one was presented within a different patterned surround
      that caused the gratings, one to each eye, to appear unequal in hue because of
      chromatic induction. The gratings were presented dichoptically with binocular
      disparity so the rivalrous gratings appeared in front of the surround. Perceptual
      alternation in hue was found for the two physically identical chromaticities.
      Stereoscopic depth also was perceived, corroborating binocular neural combination
      despite color rivalry (Treisman, 1962). The results show that color rivalry is
      resolved after color-appearance shifts caused by chromatic context, and that
      color rivalry does not require competing unequal cone excitations from the
      rivalrous stimuli.

PMID- 18321399
TI  - Neural models and physiological reality.
AB  - Neural models of retinal processing provide an important tool for analyzing
      retinal signals and their functional significance. However, it is here argued
      that in biological reality, retinal connectivity is unlikely to be as specific as
      ideal neural models might suggest. The retina is thought to provide functionally
      specific signals, but this specificity is unlikely to be anatomically complete.
      This is illustrated by examples of cone connectivity to macaque ganglion cells.
      For example, cells of the magnocellular pathway appear to avoid short-wavelength
      cone input, so that such input is negligible under normal conditions. However,
      there is anatomical, physiological, and psychophysical evidence that under
      special conditions, weak input may be revealed. Second, ideal models of how
      retinal information is centrally utilized have to take into account the
      biological reality of retinal signals. The stochastic nature of impulse trains
      modifies signal-to-noise ratio in unexpected ways. Also, non-linearities in cell
      responses make, for example, multiplexing of luminance and chromatic signals in
      the parvocellular pathway impracticable. The purpose of this analysis is to show
      than ideal neural models must confront an often more complex and nuanced
      physiological reality.

PMID- 18321400
TI  - Eel visual pigments revisited: the fate of retinal cones during metamorphosis.
AB  - During their complex life history, anguilliform eels go through a major
      metamorphosis when developing from a fresh water yellow eel into a deep-sea
      silver eel. In addition to major changes in body morphology, the visual system
      also adapts from a fresh water teleost duplex retina with rods and cones, to a
      specialized deep-sea retina containing only rods. The history of the rods is well
      documented with an initial switch from a porphyropsin to a rhodopsin (P523(2) to
      P501(1)) and then a total change in gene expression with the down regulation of a
      "freshwater" opsin and its concomitant replacement by the expression of a typical
      "deep-sea" opsin (P501(1) to P482(1)). Yellow eels possess only two spectral
      classes of single cones, one sensitive in the green presumably expressing an RH2
      opsin gene and the second sensitive in the blue expressing an SWS2 opsin gene. In
      immature glass eels, entering into rivers from the sea, the cones contain
      mixtures of rhodopsins and porphyropsins, whereas the fully freshwater yellow
      eels have cone pigments that are almost pure porphyropsins with peak
      sensitivities at about 540-545 nm and 435-440 nm, respectively. However, during
      the early stages of metamorphosis, the pigments switch to rhodopsins with the
      maximum sensitivity of the "green"-sensitive cone shifting to about 525 nm,
      somewhat paralleling, but preceding the change in rods. During metamorphosis, the
      cones are almost completely lost.

PMID- 18321401
TI  - Systematic misestimation in a vernier task arising from contrast mismatch.
AB  - Luminance signals mediated by the magnocellular (MC) pathway play an important
      role in vernier tasks. MC ganglion cells show a phase advance in their responses
      to sinusoidal stimuli with increasing contrast due to contrast gain control
      mechanisms. If the phase information in MC ganglion cell responses were utilized
      by central mechanisms in vernier tasks, one might expect systematic errors caused
      by the phase advance. This systematic error may contribute to the contrast
      paradox phenomenon, where vernier performance deteriorates, rather than improves,
      when only one of the target pair increases in contrast. Vernier psychometric
      functions for a pair of gratings of mismatched contrast were measured to seek
      such misestimation. In associated electrophysiological experiments, MC and
      parvocellular (PC) ganglion cells' responses to similar stimuli were measured to
      provide a physiological reference. The psychophysical experiments show that a
      high-contrast grating is perceived as phase advanced in the drift direction
      compared to a low-contrast grating, especially at a high drift rate (8 Hz). The
      size of the phase advance was comparable to that seen in MC cells under similar
      stimulus conditions. These results are consistent with the MC pathway supporting
      vernier performance with achromatic gratings. The shifts in vernier psychometric
      functions were negligible for pairs of chromatic gratings under the conditions
      tested here, consistent with the lack of phase advance both in responses of PC
      ganglion cells and in frequency-doubled chromatic responses of MC ganglion cells.

PMID- 18321402
TI  - The impulse response of S-cone pathways in detection of increments and
      decrements.
AB  - Impulse response functions (IRFs) were obtained from two-pulse detection
      thresholds using isoluminant stimuli that produced increments or decrements in S
      cone excitation. The pulses were chromatically modulated at constant luminance
      (based on 18 Hz heterochromatic flicker photometry). Chromatic stimuli were
      presented as a Gaussian patch (+/-1 SD = 2.3 degrees) in one of four quadrants
      around a central fixation cross on a CRT screen. Each of the two pulses (6.67 ms)
      was separated by an inter-stimulus interval (ISI) from 20 to 360 ms. Chromaticity
      of the pulses was changed from the equal-energy white of the background to a
      bluish or yellowish color along individually determined tritan lines (based on
      color matching under strong S-cone adaptation from a 420 nm background
      superimposed in Maxwellian view). Chromatic detection thresholds were determined
      by a four-alternative forced-choice method with staircases for each ISI
      interleaved in each session. Measurements were repeated in at least four sessions
      for each observer. IRFs were calculated by varying four parameters of an
      exponentially-damped sinewave. Both S-cone increment and decrement IRFs are
      characterized by a single excitatory phase and a much longer time course compared
      with IRFs derived for luminance modulation using the same apparatus and
      observers. S-cone increment IRFs are faster than S-cone decrement IRFs; the time
      to peak amplitude of S-cone increment and decrement IRFs is 50-70 and 100-120 ms,
      respectively. These results were used to derive the temporal contrast sensitivity
      for human observers of putative ON- and OFF-channels carrying signals from S
      cones.

PMID- 18321403
TI  - Amplitude of the transient visual evoked potential (tVEP) as a function of
      achromatic and chromatic contrast: contribution of different visual pathways.
AB  - We investigated how the stimulation mode influences transient visual evoked
      potentials (tVEP) amplitude as a function of contrast of achromatic and
      isoluminant chromatic gratings. The chromatic stimulation probed only responses
      to the red-green axis. Visual stimuli were monocularly presented in a 5 degrees
      diameter circle, achromatic and chromatic horizontal gratings, 1 Hz pattern
      reversal stimulation, and achromatic and chromatic gratings, 300 ms onset per 700
      ms offset stimulation. For the achromatic pattern reversal stimulation, a double
      slope function describes how the P100 amplitude varied as a function of log
      contrast which had a limb at low-to-medium contrasts and another limb at high
      contrasts. For the achromatic onset/offset stimulation, C2 amplitude saturated at
      the highest contrast tested and a single straight line described how it changed
      along most of the contrast range. Both presentation modes for chromatic gratings
      resulted in amplitude versus log contrast relations which were well described by
      single straight lines along most of the contrast range. The results may be
      interpreted as if at 2 cpd, achromatic pattern reversal stimulation evoked the
      activity of at least two visual pathways with high and low contrast sensitivity,
      respectively, while achromatic onset/offset stimulation favored the activity of a
      pathway with high contrast sensitivity. The neural activity in the M pathway is
      the best candidate to be the high contrast mechanism detected with pattern
      reversal and pattern onset/offset VEPs. The activity of color opponent pathways
      such as the P and K pathways either combined or in isolation seems to be
      responsible for VEPs obtained with isoluminant chromatic gratings at both
      presentation modes. When the amplitudes of chromatic VEPs were plotted in the
      same contrast scale as used for achromatic VEPs, chromatic contrast thresholds
      had similar values to those of the achromatic mechanism with high contrast
      sensitivity.

PMID- 18321404
TI  - Precis of The rational imagination: how people create alternatives to reality.
AB  - The human imagination remains one of the last uncharted terrains of the mind.
      People often imagine how events might have turned out "if only" something had
      been different. The "fault lines" of reality, those aspects more readily changed,
      indicate that counterfactual thoughts are guided by the same principles as
      rational thoughts. In the past, rationality and imagination have been viewed as
      opposites. But research has shown that rational thought is more imaginative than
      cognitive scientists had supposed. In The Rational Imagination, I argue that
      imaginative thought is more rational than scientists have imagined. People
      exhibit remarkable similarities in the sorts of things they change in their
      mental representation of reality when they imagine how the facts could have
      turned out differently. For example, they tend to imagine alternatives to actions
      rather than inactions, events within their control rather than those beyond their
      control, and socially unacceptable events rather than acceptable ones. Their
      thoughts about how an event might have turned out differently lead them to judge
      that a strong causal relation exists between an antecedent event and the outcome,
      and their thoughts about how an event might have turned out the same lead them to
      judge that a weaker causal relation exists. In a simple temporal sequence, people
      tend to imagine alternatives to the most recent event. The central claim in the
      book is that counterfactual thoughts are organised along the same principles as
      rational thought. The idea that the counterfactual imagination is rational
      depends on three steps: (1) humans are capable of rational thought; (2) they make
      inferences by thinking about possibilities; and (3) their counterfactual thoughts
      rely on thinking about possibilities, just as rational thoughts do. The sorts of
      possibilities that people envisage explain the mutability of certain aspects of
      mental representations and the immutability of other aspects.

PMID- 18321427
TI  - Emergency department utilization by patients not meeting Health Plan and Employer
      Data and Information Set (HEDIS) criteria for persistent asthma.
AB  - Emergency hospital utilization rates for asthma remain high despite advances in
      asthma controller medications and the presence of widely accepted asthma
      treatment guidelines. To explore this phenomenon, we analyzed administrative data
      to determine characteristics of patients seen in the emergency department (ED)
      for asthma. Complete pharmacy and diagnostic coding records were obtained from
      consecutive adults (aged 19-56 years) treated for asthma in the ED of a closed
      network health maintenance organization between April and July of 2002. Subjects
      were stratified into asthma severity categories (persistent or non-persistent)
      based on the National Committee for Quality Assurance 2006 Health Plan and
      Employer Data and Information Set (HEDIS) criteria for persistent asthma. Eighty
      one unique patients made a total of 89 ED visits for asthma during the study
      period. Of the 89 total ED visits for asthma, 44 (49%) occurred in patients that
      did not meet HEDIS criteria for persistent asthma. Of the 81 unique patients
      making asthma-related ED visits, 41 (51%) did not meet HEDIS criteria for
      persistent asthma. Over one-half (51%) of this nonpersistent population were not
      given either asthma reliever or asthma controller medications during the 12-month
      period before their index ED visit. Over the 24-month period before their index
      ED visit, 37% of nonpersistent patients were dispensed neither asthma reliever
      nor controller medications. Patients that do not meet HEDIS criteria for
      persistent asthma account for a substantial percentage of asthma-related ED
      visits. These patients have a history of low use of asthma medications before
      their ED visit.

PMID- 18321433
TI  - Gallstone disease: current therapeutic practice.
AB  - Most asymptomatic gallstone carriers require no therapy. Laparoscopic
      cholecystectomy is the best definitive therapy for symptomatic gallstone disease.
      Selective laparoscopic cholecystectomy can provide secondary prevention of
      symptoms and complications in certain instances (in a complex clinical setting
      such as sickle cell disease or to prevent gallbladder carcinoma from developing
      in those at risk with large gallstones or with a calcified gallbladder). Primary
      prevention is unproven but focuses on early identification and risk alteration to
      decrease the possibility of developing gallstones. Ursodeoxycholic acid has a
      limited role for stone dissolution but can prevent stone development in severe
      obesity during rapid weight reduction with diet or after bariatric surgery.
      Endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy
      represents the therapeutic cornerstone for managing severe pancreatitis and
      cholangitis.

PMID- 18321434
TI  - Gallbladder dyskinesia.
AB  - The most appropriate means to diagnose and manage patients with suspected
      gallbladder dyskinesia remain contentious. A major problem relates to
      difficulties in clearly identifying the features that characterize biliary-like
      pain. Conflicting reports in the literature regarding whether symptoms alone are
      reliable predictors of pain relief after cholecystectomy in patients with
      suspected gallbladder dysfunction underscore the perceived need by clinicians for
      a reliable test to help confirm a clinical suspicion of gallbladder dysfunction
      before cholecystectomy. Most studies report use of cholecystokinin
      cholescintigraphy (CCK-CS) with calculation of gallbladder ejection fraction in
      predicting symptom outcome after cholecystectomy in patients with suspected
      gallbladder dyskinesia. However, quality evidence is lacking, thereby precluding
      a definitive recommendation regarding its use. Nevertheless, CCK-CS may be useful
      when performed using a slow infusion of CCK in a well-selected patient
      population. Based on our clinical experience and interpretation of the
      literature, we currently suggest consideration of cholecystectomy to our patients
      based on high clinical suspicion. This is performed after adequate follow-up with
      trials of pharmacologic therapies and exclusion of other disease entities and
      counseling the patient on postoperative expectations. Clearly, a large,
      prospective, controlled study is needed with patients meeting the Rome definition
      of gallbladder dyskinesia, randomized to surgery or no surgery, and using
      standardized CCK-CS methods and outcome measures with long-term follow-up. This
      study would help us better understand the pathophysiology and optimal management
      of this clinically challenging condition.

PMID- 18321435
TI  - Biliary parasites: diagnostic and therapeutic strategies.
AB  - Parasitic infections of the biliary tract are a common cause of biliary
      obstruction in endemic areas. This article focuses on primary biliary parasites:
      Ascaris lumbricoides, Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis
      felineus, Dicrocoelium dendriticum, Fasciola hepatica, and Fasciola gigantica.
      Tropical and subtropical countries have the highest incidence and prevalence of
      these infections. Diagnosis is made primarily through direct microscopic
      examination of eggs in the stool, duodenal, or bile contents. Radiologic imaging
      may show intrahepatic ductal dilatation, whereas endoscopic retrograde
      cholangiopancreatography can be used diagnostically and therapeutically. However,
      oral treatment is inexpensive and effective for most of these parasites and can
      prevent untoward consequences. Primary and alternative treatments are available
      and are reviewed in this article.

PMID- 18321436
TI  - Ampullary adenoma.
AB  - Ampullary adenoma is a premalignant lesion involving the major papilla and
      surrounding mucosa of the second duodenum. These lesions may arise sporadically
      or in the setting of familial adenomatous polyposis syndrome. Ampullary adenoma
      may be found because of symptoms, at the time of adenomatous polyposis syndrome
      surveillance, or incidentally when upper endoscopy is performed for other
      reasons. Management options include observation, local or extended surgical
      resection (including pancreaticoduodenectomy), and endoscopic resection.
      Endoscopic resection is being performed more often and involves techniques
      similar to those of colonoscopic polypectomy. Preventing post-endoscopic
      resection pancreatitis is important and can be achieved with placement of
      temporary pancreatic duct stents.

PMID- 18321437
TI  - Menetrier's Disease.
AB  - Menetrier's disease is a rare acquired disorder of the fundus and body of the
      stomach (ie, oxyntic mucosa) characterized by giant hyperplastic folds, protein
      losing gastropathy, hypoalbuminemia, increased mucus secretion, and
      hypochlorhydria. Recent research implicates overproduction of transforming growth
      factor-alpha with increased signaling of the epidermal growth factor receptor
      (EGFR) in the pathogenesis. Activation of the EGFR, a transmembrane receptor with
      tyrosine kinase activity, triggers a cascade of downstream, intracellular
      signaling pathways that leads to expansion of the proliferative compartment
      within the isthmus of the oxyntic gland. The diagnosis of Menetrier's disease is
      based upon characteristic histologic changes, including foveolar hyperplasia,
      cystic dilation of pits, and reduced numbers of parietal and chief cells. The
      best treatment for Menetrier's disease is not clear. It seems reasonable to test
      and treat for cytomegalovirus and Helicobacter pylori, as 1) in children,
      evidence exists that the disease may be due to cytomegalovirus infection in up to
      one third of patients; and 2) in adults, there are anecdotal reports of
      resolution upon H. pylori eradication. More recently, therapies targeting
      increased signaling of the EGFR have shown promise, including somatostatin
      analogues and monoclonal antibodies (eg, cetuximab) directed against the EGFR. In
      refractory cases, gastrectomy is curative.

PMID- 18321438
TI  - Surgical management of gastric cancer: review and consideration for total care of
      the gastric cancer patient.
AB  - Surgical therapy remains the most effective modality in the treatment of gastric
      cancer. Staging laparoscopy with laparoscopic ultrasound may increase the
      accuracy of staging and prevent patients with unresectable gastric cancer from
      undergoing unnecessary operations. Resection of proximal and distal gastric
      cancer is best accomplished with an appropriate gastrectomy that ensures adequate
      resection margins. A D2 lymphadenectomy can be performed safely and facilitates
      the resection of the minimum 15 lymph nodes required for adequate staging.
      Adjacent organ resection should be used only in highly selected patients with R0
      resection as the goal. Palliative operations offer improved quality of life and
      symptom relief in patients with metastatic disease. Appreciation of postoperative
      quality of life after gastric resection facilitates appropriate and effective
      preoperative counseling. Surgical outcomes may be influenced by hospital volume
      and rate of adequate lymph node assessment.

PMID- 18321439
TI  - Endoscopic submucosal dissection for gastric cancer.
AB  - Endoscopic submucosal dissection (ESD) is a novel endoscopic treatment that
      enables a clinician to resect an early-stage gastric cancer in en bloc fashion.
      ESD is indicated for those cancers in which there is a high probability of en
      bloc resection and low probability of lymph node metastasis. The latter may be
      the limiting factor at institutions skilled at ESD. Several ESD techniques are
      available with similar outcomes. Thus, selection depends on operator preference
      and expertise. Gastrectomy with lymphadenectomy should be applied initially to
      those early gastric cancers with high probability of positive lymph nodes or as
      an additional treatment after ESD. Endoscopic mucosal resection (EMR) should be
      reserved for small, nonulcerated, intramucosal, differentiated cancers.
      Disadvantages of ESD in comparison with EMR are longer operation times and higher
      incidences of intraoperative bleeding and perforation, but the indication for ESD
      includes larger and ulcerative lesions not amenable to EMR.

PMID- 18321440
TI  - Prevention of NSAID-Induced Ulcers.
AB  - Cyclooxygenase-2 (COX-2) selective inhibitors were developed as gastrointestinal
      (GI) safer alternatives to nonselective NSAIDs--providing equivalent analgesic
      and anti-inflammatory efficacy. Their GI sparing is impaired by concomitant
      aspirin use, and concerns regarding adverse cardiovascular effects have emerged.
      Risk factors for NSAID-related complications include a history of ulcer disease
      or bleeding, concomitant corticosteroid or anticoagulant therapy, use of high
      dose or multiple NSAIDs (including low-dose aspirin), advanced age, and certain
      chronic diseases. If an NSAID must be used in a patient at risk, the lowest-risk
      NSAID should be used with, in many cases, cotherapy to reduce the risk for
      ulcers. COX-2 drugs have been associated with a significantly higher risk of
      vascular events than placebo or naproxen. This increase may be shared by
      nonselective NSAIDs and appears to be medication- and dose-dependent.
      Prostaglandin depletion is a central mechanism for NSAID ulcer development, and
      replacement therapy with misoprostol reduces NSAID toxicity; however, it is
      rarely used due to side effects. The acid suppression provided by traditional
      doses of histamine 2-receptor antagonists (H(2)RAs) does not prevent most NSAID
      related gastric ulcers. Despite a single study demonstrating that H(2)RAs at
      double the dose may be effective, studies comparing such high doses with
      misoprostol or proton pump inhibitors (PPIs) for preventing NSAID ulcers are not
      available. PPIs are effective at single daily doses, do not demonstrate
      tachyphylaxis, and are superior to H(2)RAs and misoprostol in reducing ulcers and
      NSAID-associated dyspepsia. NSAID choice should be predicated by an assessment of
      an individual's cardiovascular and GI risk. For those with competing
      cardiovascular and GI risks, the tradeoffs between reducing adverse GI events
      (COX-2 inhibitor instead of a nonselective NSAID) must be explicitly weighed
      against concerns about cardiovascular side effects (naproxen instead of other
      agents). Considering cost is appropriate because it may not be feasible to
      recommend the "safest" regimen in every circumstance. The cost effectiveness of
      risk-reducing therapies is intimately tied to the patient's underlying risk. For
      those at highest GI risk, using a PPI and a low-dose COX-2 inhibitor seems
      appropriate for those without high cardiovascular risk. For patients whose
      cardiovascular risk parallels or exceeds GI concerns, naproxen with a PPI is
      recommended when non-NSAID approaches fail.

PMID- 18321441
TI  - Nausea and vomiting.
AB  - Nausea and vomiting are symptoms resulting from a triggered emetic reflex. Many
      endogenous and exogenous triggering factors can activate the emetic reflex,
      making understanding difficult and therapy challenging. The key to managing most
      cases of nausea and vomiting lies in a good history and a detailed physical
      examination. Most episodes of acute vomiting (lasting < 48 hours) have an evident
      triggering factor (eg, infection, viral illness, or food poisoning) and can be
      managed by removing the triggering agent and via supportive therapy. Chronic and
      unexplained nausea and vomiting can be a challenge. The cause is often obscure
      and requires special investigation. Functional gastroduodenal disorders such as
      cyclic vomiting syndrome, functional vomiting, and chronic idiopathic nausea
      should be considered if investigations are unrevealing. Knowledge regarding
      various emetic pathways and the specific neurotransmitters involved helps to
      target therapy. Histamine-1 receptor antagonists and muscarinic antagonists are
      suitable candidates for motion sickness and labyrinthine disorders.
      Phenothiazines, 5-hydroxytryptamine-3 receptor antagonists, corticosteroids, and
      benzodiazepines have a role in postchemotherapy and postoperative nausea and
      vomiting. Cannabinoid and neurokinin-1 receptor antagonists are best reserved for
      refractory cases of nausea and vomiting. Motilin agonists and metoclopramide are
      useful for treating impaired gastric motility disorders.

PMID- 18321442
TI  - Oocyte maturation. Basic and clinical aspects of in vitro maturation (IVM) with
      special emphasis of the role of FF-MAS.
AB  - In Vitro maturation (IVM) of human oocytes is an emerging infertility treatment
      with great promise. To be successful this future assisted reproductive technology
      must entail both nuclear and cytoplasmic maturation of the oocytes and give rise
      to human embryos that have the same developmental potential as embryos resulting
      from the golden standard of human IVF. The aspiration of immature oocytes from
      small to medium size antral follicles followed by their maturation In Vitro
      present an attractive alternative to the hormonal stimulation of patients in In
      Vitro fertilization (IVF) treatment, since administration of exogenous hormones
      is a costly treatment and may cause severe health problems. Of the long list of
      side effect and health concern ovarian hyper-stimulation syndrome (OHSS) is by
      far the most severe although long term effect on cancer prevalence is another
      concern. Another potential group of patients that could benefit from future IVM
      treatments are the young women undergoing anticancer therapy (radiation- or
      chemotherapy). Thus, ovarian and oocyte cryopreservation techniques are emerging,
      however such treatments can only be fully realized when IVM becomes an efficient
      means of obtaining healthy birth. At present, the In Vitro maturation techniques
      are highly successful in mice, variable successful in domestic species and still
      regarded experimental in the human clinic due to suboptimal fertilization rates
      and embryo quality. This review discusses comparative studies of the processes of
      oocyte maturation In Vivo and In Vitro, in various mammalian species including
      human. Among the substances that have been reported to influence oocyte
      maturation there is an interesting endogenous signaling molecule: FF-MAS (4,4
      dimethyl-5 alpha-cholest-8,14,24-trien-3 beta -ol), an intermediate in the
      cholesterol biosynthetic pathway present in all cells. This review gives special
      focus to FF-MAS, the effect seen in animal and human studies so far and its
      potential use in treatment of human infertility is being discussed, including
      both the safety and efficacy issues that need to be addressed. It is being
      reviewed how FF-MAS and related MAS analogues by our group and other scientific
      groups have been observed to mediate a dose-dependant response on both the
      nuclear maturation and especially the cytoplasmic maturation during oocyte
      maturation In Vitro thus giving rise to pre-embryos of higher developmental
      potential. Studies are reviewed regarding the family of meiosis activating
      sterols, its In Vivo regulation by gonadotropins (especially LH) and suggestions
      to the signaling pathways as the putative MAS receptor eliciting the important
      cytoplasmic maturation signaling cascade that involves mos/MAP kinase. The
      pharmacological effect of synthetic FF-MAS has been observed in various models
      and species, including murine, porcine and humane oocytes. Finally, the
      chromosome status of IVM human oocytes has been the focus of a large prospective
      clinical trial, documenting that FF-MAS acting on human oocytes during In Vitro
      maturation presents a safe procedure evaluated on numerical chromosome aberration
      rates in metaphase-II oocytes. In conclusion the In Vitro maturation of human
      oocytes is already now a valuable clinical treatment alternative for a subset of
      infertile patients, especially the Polycystic Ovarian Syndrome (PCOS) patients.
      IVM has the promise of being tomorrow's gold standard in treatment of human
      infertility if most of the important components of oocyte maturation are
      understood and can be adequately addressed In Vitro. Considering the present low
      frequency of successful fertilization and pre-implantation development following
      In Vitro maturation of human oocytes, the addition of FF-MAS or MAS analogues to
      the maturation medium to improve the cytoplasmic maturation and to yield higher
      quality pre-embryos may prove highly beneficial.

PMID- 18321443
TI  - The role of calcium-sensing receptor and signalling pathways in the
      pathophysiology in two in vitro models of malignant hypercalcemia: the rat rice H
      500 Leydig testis cancer and prostate cancer (PC-3) cells. Expression and
      regulation of pituitary tumor transforming gene in Leydig testis cancer and
      astrocyte and astrocytoma cells.
AB  - The calcium-sensing receptor (CaR) is a seven transmembrane receptor incorporated
      into the cell membrane that is sensitive to extracellular calcium and other
      cations. The finding that the CaR is expressed on cancer cells has opened the
      door to a new understanding of the role of extracellular calcium as a
      promalignant stimulus through the CaR and its signaling apparatus as demonstrated
      in this thesis. I found, in a model of humoral hypercalcemia of malignancy (HHM),
      that stimulation of the CaR worsens the promalignant features of the testicular H
      500 Leydig cancer cells that were used in my studies. The CaR upregulated the
      release of parathyroid hormone-related peptide (PTHrP), the main mediator of
      hypercalcemia in HHM. The growth rate of the tumor was also increased by
      stimulation of the CaR, as DNA synthesis and protection against apoptosis were
      enhanced. The oncogene, pituitary tumor-transforming gene (PTTG), was found to be
      upregulated by the CaR in the H-500 cells, whereas calcium had no effect on PTTG
      expression in the U-87 astrocytoma cell line, but other proproliferative agents
      did upregulate PTTG in the U-87 cells. This makes PTTG a potential marker of
      malignancy and a therapeutic target in cancer, where the CaR is promalignant.
      Nitric oxide synthase (NOS) exists in three isoforms, and I found that the CaR
      upregulated the inducible NOS but not the two other isoforms. This upregulation
      was accompanied by an increased production of NO. NO has been shown to be
      potentially promalignant, although such a role was not established in the H-500
      cells. Therefore, the CaR stimulates several promalignant features in the H-500
      cells. In turn, blocking these effects by targeting a proximal downstream
      signaling molecule of the CaR may be a future clinical approach, since blocking
      the CaR might have too many adverse effects on calcium homeostasis. In
      conclusion, the CaR plays diverse roles in cancer-acting as an inhibitor of cell
      proliferation in the colon crypt cells giving rise to colon cancer but as a
      promalignant receptor in most other cancer types, including Leydig cell cancers.

PMID- 18321444
TI  - Sun exposure behaviour among subgroups of the Danish population. Based on
      personal electronic UVR dosimetry and corresponding exposure diaries.
AB  - Solar ultraviolet radiation (UVR) is known to be the most important etiological
      factor in skin cancer development. The main objective of this thesis was to
      achieve an objective, basic knowledge of the individual UVR exposure dose pattern
      and to reveal the factors and with which power they influence on the UVR dose
      among the Danes. Eight open prospective, observational studies and one study
      analyzing the compliance and reliability of data were performed in healthy Danish
      volunteers with an age range of 4-68 years. The subjects were chosen to cover an
      age span group of children, adolescents, and indoor workers and in addition,
      groups with expected high UVR exposure, sun worshippers, golfers, and gardeners.
      We developed a personal, electronic UVR dosimeter in a wristwatch (SunSaver). The
      subjects wore the UVR dosimeter that measured time-stamped UVR doses in standard
      erythema doses (SED) and completed diaries with data on their sun exposure
      behaviour. This resulted in corresponding UVR dosimeter and diary data from 346
      sun-years where one sun-year is one person participating in one summer half-year
      (median 119 days). The annual UVR doses were calculated based on the personal and
      ambient measured UVR doses. We found a huge variation in annual UVR exposure dose
      within the total population sample, median 173 SED (range, 17-980 SED). The inter
      group variation in annual UVR dose was from median 132 SED among indoor workers
      to median 224 SED among gardeners. No significant correlation was found between
      annual UVR dose and age either within the total population or among the adults.
      But the subjects below 20 years of age had an increase in annual UVR dose of 5
      SED per year. Young people before the age of 20 years did not get a higher
      proportion of the lifetime UVR dose than expected (25%) when assuming a life
      expectancy of 80 years. There was no significant difference in annual UVR dose
      between males and females in the total population sample. But, among children,
      girls received a significantly higher UVR dose than boys due to more days with
      risk behaviour (sunbathing or exposing shoulders outdoors). This exposure
      pattern, with females having more risk behaviour than males, was also found among
      adolescents and adults. Sunbathing or exposing shoulders (risk behaviour) outside
      the beach resulted in a median of 2.5 SED per day in northern Europe and 3.2 SED
      per day in southern Europe, while the corresponding values were 4.6 SED and 6.9
      SED per day at the beach. UVR doses above 10 SED per day were connected with risk
      behaviour. The subjects had a median of 13 days with risk behaviour (range, 0-93
      days). The subjects used sunscreen on a median of five days (range, 0-130 days),
      but have a median of seven days with risk behaviour without sunscreen applied
      (range, 0-47 days). They had a median of one sunburn per sun-year (range 0-10).
      Fifty percent of the UVR dose was received between 12.00 and 15.00. Only the
      gardeners received the main part of their UVR dose on workdays. Conclusions : -
      High UVR doses are connected with risk behaviour. Reduction of cumulative
      lifetime UVR dose could be obtained by minimizing risk behaviour. - Sunburns were
      highly correlated to risk behaviour. - Use of sunscreen correlated with days
      "sunbathing with the intention to tan", indicating that sunscreens were used to
      avoid sunburn during risk behaviour. - Scheduling lunch breaks and other breaks
      indoors at noon, where ambient UVR peaks, could reduce the occupational UVR
      exposure significantly. - In the winter-half-year in Denmark. the UVR dose
      received from solar exposure is negligible and no UVR precautions are needed.
      This study documented that high subject compliance rate and data reliability
      could be obtained in long-time UVR dosimeter study as ours by being service
      minded but persistent, offering dosimeter maintenance service within 24 hours and
      scrutinizing data for errors and mistakes just after data collection.

PMID- 18321445
TI  - SurveillanceMapper: a simple method for creating an overview of quality data.
AB  - INTRODUCTION: The amount of quality data continues to increase. To help
      prioritise resources for quality improvement, managers need thorough reviews to
      help them decide which indicators are most important to improve. The reality is
      that data is presented in piles of reports and hundreds of tables and graphs that
      are very time-consuming to go through and that rarely result in a simple
      comprehensive overview. This paper presents an empirically tested tool to create
      a simple overview of complex quality data. METHODOLOGY: Data comes from a
      questionnaire-based patient satisfaction survey of 13,129 patients and 1,589
      staff members at Ribe County Hospital. A method is described: how to use colour
      coding in order to present the results for 16 indicators, measured both by
      patients and three staff member groups, for 28 departments and 46 ambulatories,
      in one page. RESULTS: Data for mean satisfaction scores on all questions are
      shown for each department in a core map. Aggregated departmental mean
      satisfaction scores are then calculated, as are hospital mean scores for each
      question. The same is done for staff members' evaluation and for outpatient care.
      Few problems are universal and most of the problematic scores are related to a
      minority of departments, calling for local activities to improve quality.
      Diversity seems to be the rule. CONCLUSIONS: The SurveillanceMapper-tool proved
      effective for handling the complexity of quality measures. It is easy to
      translate hundreds of graphs and tables into the SurveillanceMapper-tool format.
      The method facilitates easy spotting areas for quality improvements and
      evaluating the results of intervention.

PMID- 18321446
TI  - Advanced textile materials and biopolymers in wound management.
AB  - New generation medical textiles are an important growing field with great
      expansion in wound management products. Virtually new products are coming but
      also well known materials with significantly improved properties using advanced
      technologies and new methods are in the centre of research which are highly
      technical, technological, functional, and effective oriented. The key qualities
      of fibres and dressings as wound care products include that they are
      bacteriostatic, anti-viral, fungistatic, non-toxic, high absorbent, non-allergic,
      breathable, haemostatic, biocompatible, and manipulatable to incorporate
      medications, also provide reasonable mechanical properties. Many advantages over
      traditional materials have products modified or blended with also based on
      alginate, chitin/chitosan, collagen, branan ferulate, carbon fibres. Textile
      structures used for modern wound dressings are of large variety: sliver, yarn,
      woven, non-woven, knitted, crochet, braided, embroidered, composite materials.
      Wound care also applies to materials like hydrogels, matrix (tissue engineering),
      films, hydrocolloids, foams. Specialized additives with special functions can be
      introduced in advanced wound dressings with the aim to absorb odours, provide
      strong antibacterial properties, smooth pain and relieve irritation. Because of
      unique properties as high surface area to volume ratio, film thinness, nano scale
      fibre diameter, porosity, light weight, nanofibres are used in wound care. The
      aim of this study is to outline and review the latest developments and advance in
      medical textiles and biopolymers for wound management providing the overview with
      generalized scope about novelties in products and properties.

PMID- 18321451
TI  - This obscure herb works for the common cold.

PMID- 18321452
TI  - 10 derm mistakes you don't want to make.

PMID- 18321453
TI  - Getting patients to exercise more: a systematic review of underserved
      populations.

PMID- 18321454
TI  - Pruritic blisters on legs and feet.

PMID- 18321455
TI  - Vaccine update: new CDC recommendations from 2007.

PMID- 18321456
TI  - Clinical inquiries. What are the causes of elevated TSH in a newborn?

PMID- 18321457
TI  - Clinical inquiries. What is the differential diagnosis of chronic leg edema in
      primary care?

PMID- 18321458
TI  - Clinical inquiries. Is osteopathic manipulation effective for headaches?

PMID- 18321459
TI  - Clinical inquiries. What's the best drug treatment for premature ejaculation?

PMID- 18321460
TI  - Clinical inquiries. When should you admit a patient with suspected CAP?

PMID- 18321462
TI  - Long-term outcomes and social independence level after arterial switch operation.
AB  - OBJECTIVES: Various issues regarding the long-term survivors of arterial switch
      operation (ASO) have been clarified according to the improvement of surgical
      mortality. We reviewed the long-term results and social independence level after
      ASO. METHODS: Two hundred and four (204) patients who had undergone ASO more than
      15 years ago were studied retrospectively. ASO was performed as a primary
      operation (group I, n=99) or as a secondary operation (group II, n=105). Lecompte
      procedure was performed in 197 patients, modified Aubert procedure in 5, and
      original Jatene procedure in 2. RESULTS: There were 11 late deaths. Kaplan-Meier
      survival rate (not including operative deaths) was 94.9% at 10 years and 94.9% at
      15 years in group I, and 96.9% at 10 years and 94.4% at 15 years in group II.
      Forty-eight reoperations were performed (aortic valve replacement in 6, aortic
      valvoplasty in 2, Konno procedure in 1, double valve replacement in 1, right
      ventricular outflow tract reconstruction in 35). The reoperation-free rate
      including late death was 82.2% at 10 years and 75.7% at 15 years in group I, and
      88.2% at 10 years and 78.1% at 15 years in group II. One hundred and seventy
      eight patients were classified as NYHA class I and 7 patients as class II. All
      the patients except those with mental disorder (1) or neurodevelopmental
      impairment (3) were attending school or working. There was no significant
      difference in left ventricular function between group I and II, both showing
      values within the normal range. CONCLUSIONS: The long-term (>15 years) outcome of
      ASO survivors was satisfactory. Most patients showed excellent cardiac function
      and were socially independent.

PMID- 18321461
TI  - Effects of acute ischemic mitral regurgitation on three-dimensional mitral
      leaflet edge geometry.
AB  - BACKGROUND: Improved quantitative understanding of in vivo leaflet geometry in
      ischemic mitral regurgitation (IMR) is needed to improve reparative techniques,
      yet few data are available due to current imaging limitations. Using marker
      technology we tested the hypotheses that IMR (1) occurs chiefly during early
      systole; (2) affects primarily the valve region contiguous with the myocardial
      ischemic insult; and (3) results in systolic leaflet edge restriction. METHODS:
      Eleven sheep had radiopaque markers sutured as five opposing pairs along the
      anterior (A(1)-E(1)) and posterior (A(2)-E(2)) mitral leaflet free edges from the
      anterior commissure (A(1)-A(2)) to the posterior commissure (E(1)-E(2)).
      Immediately postoperatively, biplane videofluoroscopy was used to obtain 4D
      marker coordinates before and during acute proximal left circumflex artery
      occlusion. Regional mitral orifice area (MOA) was calculated in the anterior (Ant
      MOA), middle (Mid-MOA), and posterior (Post-MOA) mitral orifice segments during
      early systole (EarlyS), mid systole (MidS), and end systole (EndS). MOA was
      normalized to zero (minimum orifice opening) at baseline EndS. Tenting height was
      the distance of the midpoint of paired markers to the mitral annular plane at
      EndS. RESULTS: Acute ischemia increased echocardiographic MR grade (0.5+/-0.3 vs
      2.3+/-0.7, p<0.01) and MOA in all regions at EarlyS, MidS, and EndS: Ant-MOA (7+/
      10 vs 22+/-19 mm(2), 1+/-2 vs 18+/-16 mm(2), 0 vs 17+/-15 mm(2)); Mid-MOA (9+/-13
      vs 25+/-17 mm(2), 3+/-6 vs 21+/-19 mm(2), 0 vs 25+/-17 mm(2)); and Post-MOA (8+/
      10 vs 25+/-16, 2+/-4 vs 22+/-13 mm(2), 0 vs 23+/-13 mm(2)), all p<0.05. There was
      no change in MOA throughout systole (EarlyS vs MidS vs EndS) during baseline
      conditions or ischemia. Tenting height increased with ischemia near the central
      and the anterior commissure leaflet edges (B(1)-B(2): 7.1+/-1.8mm vs 7.9+/-1.7
      mm, C(1)-C(2): 6.9+/-1.3mm vs 8.0+/-1.5mm, both p<0.05). CONCLUSIONS: MOA during
      ischemia was larger throughout systole, indicating that acute IMR in this setting
      is a holosystolic phenomenon. Despite discrete postero-lateral myocardial
      ischemia, Post-MOA was not disproportionately larger. Acute ovine IMR was
      associated with leaflet restriction near the central and the anterior commissure
      leaflet edges. This entire constellation of annular, valvular, and subvalvular
      ischemic alterations should be considered in the approach to mitral repair for
      IMR.

PMID- 18321464
TI  - Organically modified silica: synthesis and applications due to its surface
      interaction with organic molecules.
AB  - Silica gels can be chemically modified using organic precursors producing
      organically modified silica (ORMOSIL), a class of novel materials for hosting
      varieties of organic and inorganic substrates. Ormosil matrixed materials show an
      enhanced activity during catalysis, photochemical activities like absorption and
      emission, electrochemical sensitivities, sensing of gases, solvents, pH of
      solution and biomolecules, etc. Ormosil-based materials can be used as efficient
      protective coatings and can be utilized in designing wave guides that can carry
      out excellent photonic transmission of information. The synthetic and chemical
      modification of ormosil and some of the above applications have been discussed.

PMID- 18321465
TI  - Ranibizumab combined with verteporfin photodynamic therapy in neovascular age
      related macular degeneration (FOCUS): year 2 results.
AB  - PURPOSE: To assess the efficacy and adverse-events profile of combined treatment
      with ranibizumab and verteporfin photodynamic therapy (PDT) in patients with
      predominantly classic choroidal neovascularization (CNV) secondary to neovascular
      age-related macular degeneration. DESIGN: Two-year, multicenter, randomized,
      single-masked, controlled study. METHODS: Patients received monthly intravitreal
      injections of ranibizumab 0.5 mg (n = 106) or sham injections (n = 56). All
      patients received PDT on day zero, then quarterly as needed. Efficacy assessment
      included changes in visual acuity (VA) and lesion characteristics and PDT
      frequency. Adverse events were summarized by incidence and severity. RESULTS: At
      month 24, 88% of ranibizumab + PDT patients had lost <15 letters from baseline VA
      (vs 75% for PDT alone), 25% had gained >or=15 letters (vs 7% for PDT alone), and
      the two treatment arms differed by 12.4 letters in mean VA change (P < .05 for
      all between-group differences). The VA benefit of adding ranibizumab to PDT in
      year one persisted through year two. On average, ranibizumab + PDT patients
      exhibited less lesion growth and greater reduction of CNV leakage and subretinal
      fluid accumulation, and required fewer PDT retreatments, than PDT-alone patients
      (mean = 0.4 vs 3.0 PDT retreatments). Endophthalmitis and serious intraocular
      inflammation occurred, respectively, in 2.9% and 12.4% of ranibizumab + PDT
      patients and 0% of PDT-alone patients. Incidences of serious nonocular adverse
      events were similar in the two treatment groups. CONCLUSIONS: Through two years,
      ranibizumab + PDT was more effective than PDT alone and had a low rate of
      associated adverse events.

PMID- 18321466
TI  - Intravitreal bevacizumab for choroidal neovascularization in ocular
      histoplasmosis.
AB  - PURPOSE: To define the role of intravitreal bevacizumab in individuals with
      choroidal neovascularization (CNV) resulting from Ocular Histoplasmosis syndrome
      (OHS). DESIGN: Retrospective chart review of a surgical therapy. METHODS: We
      reviewed the course of 28 eyes of 28 patients who underwent intravitreal
      injection of bevacizumab for treatment of CNV secondary to OHS. Outcome was
      measured by pretreatment and posttreatment visual acuity (VA). RESULTS: The
      average pretreatment logarithm of the minimum angle of resolution (logMAR) VA was
      0.65 (Snellen equivalent of 20/88). Mean follow-up was 22.43 weeks with an
      average of 1.8 intravitreal injections. Average final logMAR VA was 0.43 (Snellen
      equivalent of 20/54). Twenty eyes (71%) experienced an increase in central VA,
      whereas four eyes (14%) were unchanged and four eyes (14%) experienced a decrease
      in vision. CONCLUSIONS: Intravitreal bevacizumab may improve or stabilize VA in a
      significant majority of patients with neovascular complications of OHS (24 eyes
      [85.7%] in our study population).

PMID- 18321467
TI  - Smoking as a risk factor for cystoid macular edema complicating intermediate
      uveitis.
AB  - PURPOSE: To describe risk factors for the presence of cystoid macular edema (CME)
      among patients presenting with intermediate uveitis. DESIGN: Cross-sectional
      study. METHODS:  SETTINGS: Single-center, academic practice. STUDY POPULATION:
      Two hundred and eight patients with intermediate uveitis evaluated from July 1,
      1984 through September 30, 2006. PROCEDURES: Clinical and demographic data were
      entered retrospectively into a database and analyzed. OUTCOME MEASURES: Presence
      of CME at presentation to our clinic; risk factors for presenting with CME.
      RESULTS: Of the 208 patients, 74% had bilateral intermediate uveitis, yielding
      363 affected eyes. Eighty-nine patients (43%) had CME in at least one eye at the
      time of presentation to our clinic. After controlling for potentially confounding
      variables including demographics, duration of disease, active intraocular
      inflammation, history of diabetes mellitus or hypertension, and presence of
      epiretinal membrane, actively smoking at presentation was associated with a four
      fold increased risk of CME at presentation vs never smoking (odds ratio (OR),
      3.90; 95% confidence interval (CI), 1.43, 10.66; P = .008). Former smoking also
      appeared to increase the risk of CME at presentation in the multivariate
      analysis, but the result was of borderline statistical significance (OR, 1.97;
      95% CI, 0.99, 3.94; P = .055). After adjusting for confounding, there was a 4%
      increased risk of CME at presentation for each cigarette smoked per day (OR,
      1.04; 95% CI, 1.01, 1.7; P = .005). CONCLUSIONS: CME was a common structural
      ocular complication observed in our cohort. Current smoking was associated with a
      dose-dependent increased risk of having CME at the time of presentation to our
      clinic.

PMID- 18321468
TI  - Driver fatigue during extended rail operations.
AB  - OBJECTIVES: Relay is an effective mode of freight transportation within
      Australia. Relay requires two crews to drive the train continuously from one
      specified destination to another and return with crews working in alternating
      shifts. The aim of the current investigation was to assess fatigue levels during
      extended relay operations. METHODS: Nine drivers participated and data were
      collected from 16 four-day trips. Fatigue was assessed objectively and
      subjectively prior to and following each trip and before and after each 8h shift.
      RESULTS: Analyses revealed a trend for elevated fatigue at the end of each shift.
      Designated 8h rest periods appeared sufficient to reduce fatigue to levels
      recorded prior to departure and prevent accumulation of fatigue across the trip.
      CONCLUSIONS: Drivers seemed to cope well with the 8h rotating sleep/wake regime.
      While fatigue did not observably accumulate, it is possible that operational
      measures may better reflect fatigue experienced over the course of each trip.

PMID- 18321469
TI  - Negative self-focused cognitions mediate the effect of trait social anxiety on
      state anxiety.
AB  - The cognitive model of social anxiety predicts that negative self-focused
      cognitions increase anxiety when anticipating social threat. To test this
      prediction, 36 individuals were asked to anticipate and perform a public-speaking
      task. During anticipation, negative self-focused cognitions or relaxation were
      experimentally induced while self-reported anxiety, autonomic arousal (heart
      rate, heart rate variability, skin conductance level), and acoustic eye-blink
      startle response were assessed. As predicted, negative self-focused cognitions
      mediated the effects of trait social anxiety on self-reported anxiety and heart
      rate variability during negative anticipation. Furthermore, trait social anxiety
      predicted increased startle amplitudes. These findings support a central
      assumption of the cognitive model of social anxiety.

PMID- 18321470
TI  - Expansion in the provision of psychological treatment in the United Kingdom.

PMID- 18321471
TI  - New players on the center stage: sphingosine 1-phosphate and its receptors as
      drug targets.
AB  - The recent identification of a cellular balance between ceramide and sphingosine
      1-phosphate (S1P) as a critical regulator of cell growth and death has stimulated
      increasing research effort to clarify the role of ceramide and S1P in various
      diseases associated with dysregulated cell proliferation and apoptosis. S1P acts
      mainly, but not exclusively, by binding to and activating specific cell surface
      receptors, the so-called S1P receptors. These receptors belong to the class of G
      protein-coupled receptors that constitute five subtypes, denoted as S1P(1)
      S1P(5), and represent attractive pharmacological targets to interfere with S1P
      action. Whereas classical receptor antagonists will directly block S1P action,
      S1P receptor agonists have also proven useful, as recently shown for the
      sphingolipid-like immunomodulatory substance FTY720. When phosphorylated by
      sphingosine kinase to yield FTY720 phosphate, it acutely acts as an agonist at
      S1P receptors, but upon prolonged presence, it displays antagonistic activity by
      specifically desensitizing the S1P(1) receptor subtype. This commentary will
      cover the most recent developments in the field of S1P receptor pharmacology and
      highlights the potential therapeutic benefit that can be expected from these
      novel drug targets in the future.

PMID- 18321472
TI  - Inhibition of uptake 2 (or extraneuronal monoamine transporter) by
      normetanephrine potentiates the neurochemical effects of venlafaxine.
AB  - Two distinct norepinephrine (NE) transporter mechanisms (uptake 1 and uptake 2)
      regulate extracellular NE concentrations. An association has been observed
      between the gradual improvement in patients treated with antidepressants that
      inhibit the NE transporter (NET/uptake 1) and increases in urinary
      normetanephrine, the O-methylated NE metabolite and potent inhibitor of uptake 2.
      These observations led to the hypothesis that increased levels of
      normetanephrine, and consequently inhibition of uptake 2, may partly be
      responsible for the clinical efficacy of some antidepressants. To investigate
      this hypothesis, we employed microdialysis techniques in the rat frontal cortex
      to monitor extracellular changes in normetanephrine following chronic
      administration of the clinically effective antidepressant, venlafaxine (a
      serotonin (5-HT) and NE reuptake inhibitor). We evaluated the neurochemical
      effects of inhibiting uptake 2 alone, or in conjunction with venlafaxine, on
      extracellular levels of NE and 5-HT. Chronic venlafaxine administration (14 days,
      10 mg/kg, s.c.) elicited significant increases in cortical NE and 5-HT while
      producing a non-significant trend to increase cortical levels of normetanephrine.
      Additional studies revealed that combining normetanephrine with venlafaxine (10
      mg/kg, i.p.), at a dose of normetanephrine (10 mg/kg, i.p.) that did not produce
      changes in extracellular levels of NE on its own, potentiated antidepressant
      induced increases in extracellular NE. We also report mouse behavioral data
      involving the tail suspension test that complement the neurochemical
      observations. These preclinical findings, taken together, suggest that inhibiting
      both uptake 1 and uptake 2 via venlafaxine and normetanephrine, respectively,
      elicits a greater increase in cortical levels of NE than inhibiting either
      transporter alone.

PMID- 18321473
TI  - Cilostazol alleviates cerebral small-vessel pathology and white-matter lesions in
      stroke-prone spontaneously hypertensive rats.
AB  - Small-vessel pathology is believed to have a critical role in cerebrovascular
      white-matter (WM) lesions. However, the cellular aspect of vascular pathology,
      including the phenotypic modulation of smooth-muscle cells (SMCs) and its role in
      the small-vessel disease, remains undefined. The involvement or otherwise of the
      phenotypic modulation of SMCs in cerebral small-vessel pathology has been
      investigated, and the effect of cilostazol on both the small vessels and the WM
      lesions has been determined in stroke-prone spontaneously hypertensive rats
      (SHRSP). Male SHRSP and Wistar Kyoto rats were used. SHRSP were divided into two
      groups: the cilostazol-treated (20-week treatment) and vehicle-treated groups.
      Small-vessel pathology was analyzed using both histopathology and
      immunohistochemistry for smooth-muscle actin and nonmuscle myosin heavy chain
      (SMemb, a marker for the synthetic phenotype of SMC). The pathological changes in
      the WM were quantified in terms of the numerical density of activated microglia
      and the degree of WM lesions. Vascular wall thickening and perivascular fibrosis,
      determined by the wall area/lumen area ratio and the collagen area/total vessel
      area ratio, respectively, showed an increase in the vehicle-treated SHRSP, and
      this increase was significantly attenuated by cilostazol treatment. The
      percentage of small vessels immunopositive for SMemb was also reduced by
      cilostazol treatment. In the cilostazol-treated SHRSP, microglial activation and
      the degree of WM lesions were attenuated compared with the vehicle-treated SHRSP.
      The results indicated that cilostazol attenuates the phenotypic modulation of SMC
      associated with cerebral small-vessel pathology and WM lesions without causing
      changes in the blood pressure.

PMID- 18321474
TI  - Daily oscillation of gene expression in the retina is phase-advanced with respect
      to the pineal gland.
AB  - The photoreceptive retina and the non-photoreceptive pineal gland are components
      of the circadian and the melatonin forming system in mammals. To contribute to
      our understanding of the functional integrity of the circadian system and the
      melatonin forming system we have compared the daily oscillation of the two
      tissues under various seasonal lighting conditions. For this purpose, the 24-h
      profiles of the expression of the genes coding for arylalkylamine N
      acetyltransferase (AA-NAT), nerve growth factor inducible gene-A (NGFI-A), nerve
      growth factor inducible gene-B (NGFI-B), retinoic acid related orphan receptor
      beta (RORbeta), dopamine D4 receptor, and period2 (Per2) have been simultaneously
      recorded in the retina and the pineal gland of rats under short day (light/dark
      8:16) and long day (light/dark 16:8) conditions. We have found that the cyclical
      patterns of all genes are phase-advanced in the retina, often with a lengthened
      temporal interval under short day conditions. In both tissues, the AA-NAT gene
      expression represents an indication of the output of the relevant pacemakers. The
      temporal phasing in the AA-NAT transcript amount between the retina and the
      pineal gland is retained under constant darkness suggesting that the intrinsic
      self-cycling clock of the retina oscillates in a phase-advanced manner with
      respect to the self-cycling clock in the suprachiasmatic nucleus, which controls
      the pineal gland. We therefore conclude that daily rhythms in gene expression in
      the retina are phase-advanced with respect to the pineal gland, and that the same
      temporal relationship appears to be valid for the self-cycling clocks influencing
      the tissues.

PMID- 18321475
TI  - Involvement of batrachotoxin binding sites in ginsenoside-mediated voltage-gated
      Na+ channel regulation.
AB  - Recently, we showed that the 20(S)-ginsenoside Rg3 (Rg3), an active ingredient of
      Panax ginseng, inhibits rat brain NaV1.2 channel peak currents (INa).
      Batrachotoxin (BTX) is a steroidal alkaloid neurotoxin and activates NaV channels
      through interacting with transmembrane domain-I-segment 6 (IS6) of channels.
      Recent report shows that ginsenoside inhibits BTX binding in rat brain membrane
      fractions. However, it needs to be confirmed whether biochemical mechanism is
      relevant physiologically and which residues of the BTX binding sites are
      important for ginsenoside regulations. Here, we demonstrate that mutations of BTX
      binding sites such as N418K and L421K of rat brain NaV1.2 and L437K of mouse
      skeletal muscle NaV1.4 channel reduce or abolish Rg3 inhibition of I(Na) and
      attenuate Rg3-mediated depolarizing shift of the activation voltage and use
      dependent inhibition. These results indicate that BTX binding sites play an
      important role in modifying Rg3-mediated Na+ channel properties.

PMID- 18321476
TI  - Modulation of spontaneous hippocampal synaptic events with 5-hydroxyindole, 4OH
      GTS-21, and rAAV-mediated alpha7 nicotinic receptor gene transfer.
AB  - One approach to treatment of negative cognitive effects associated with
      Alzheimer's disease and schizophrenia may involve activation of neuronal alpha7
      nicotinic acetylcholine receptors (nAChRs). We used the alpha7-selective partial
      agonist 3-(4-hydroxy, 2-methoxy-benzylidene)anabaseine (4OH-GTS-21), the alpha7
      modulator 5-hydroxyindole (5-HI), and recombinant adeno-associated virus (rAAV)
      mediated alpha7 gene transfer in order to test the hypothesis whether combining
      these strategies would significantly increase indirect measures of alpha7 nAChR
      function, including measures of spontaneous synaptic events in CA1 pyramidal
      cells. 5-HI (1 mM), and 5-HI (1 mM)+4OH-GTS-21 (5 microM) increased the frequency
      of APV- and NBQX-sensitive currents, while 5-HI+4OH-GTS-21 increased the
      frequency and amplitude of bicuculline-sensitive currents. Effects on EPSCs were
      blocked with tetrodotoxin (TTX) (1 microM), but not by methyllycaconitine (MLA)
      (50 nM). Neither TTX nor MLA reduced the potentiation of IPSC frequencies.
      However, TTX blocked, and in some cases MLA reduced, the potentiation of IPSC
      amplitudes. These data suggest that effects of 5-HI+4OH-GTS-21 on EPSC frequency
      were associated with action potential-dependent transmitter release produced by
      5HI, and that potentiation of IPSC amplitudes resulted at least in part, from
      activation of alpha7 nAChRs. Finally, rAAV-mediated alpha7 gene transfer did not
      alter the magnitude of effects produced by 5-HI or 5-HI+4OH-GTS-21. Thus,
      although we previously showed that direct measures of alpha7 nAChR function were
      enhanced by alpha7 gene transfer, indirect measures of alpha7 nAChRs function
      were not significantly enhanced by combining alpha7 gene transfer with either
      agonist activation or positive allosteric modulation of alpha7 nAChRs.

PMID- 18321477
TI  - Impaired thymopoiesis in interleukin-7 receptor transgenic mice is not corrected
      by Bcl-2.
AB  - Murine thymocytes down-regulate IL-7 responsiveness following beta-selection and
      reacquire sensitivity after positive selection. To assess the potential
      consequences of IL-7 signaling during this phase of development, transgenic IL-7
      receptor alpha (IL-7Ralpha) mice were evaluated for IL-7 responsiveness as gauged
      by STAT-5 phosphorylation. Transgenic IL-7Ralpha expression increased the
      percentage of thymocytes responsive to IL-7 yet resulted in a decrease in total
      thymic cellularity. Aberrant thymocyte development in transgenic mice was first
      manifested by a reduction of DN3 thymocytes that correlated with lower Bcl-2
      expression. Surprisingly, transgenic restoration of Bcl-2 expression did not
      correct thymic hypocellularity induced by IL-7Ralpha overexpression. These
      findings demonstrate that failure to appropriately downregulate IL-7Ralpha
      expression interferes with thymocyte development past the pro-T stage resulting
      in significantly lower levels of mature thymocytes.

PMID- 18321478
TI  - Classification of acute myocardial ischemia by artificial neural network using
      echocardiographic strain waveforms.
AB  - Echocardiographic strain waveforms are highly variable, so their interpretation
      is experience-dependent and subjective. We tested whether an artificial neural
      network (ANN) can distinguish between strain waveforms obtained at baseline and
      during experimentally induced acute ischemia. An open-chest model of coronary
      occlusion and acute ischemia was used in 14 adult pigs. Strain waveforms were
      obtained using a GE Vivid 7 ultrasound system. An ANN design was implemented in
      MATLAB, and backpropagation and "leave-one-out" processes were used to train and
      test it. Specificity of 86% and sensitivity of 87% suggest that ANNs could aid in
      diagnostic prescreening of echocardiographic strain waveforms.

PMID- 18321479
TI  - A nutritional model of late embryonic vitamin A deficiency produces defects in
      organogenesis at a high penetrance and reveals new roles for the vitamin in
      skeletal development.
AB  - Vitamin A plays an essential role in vertebrate embryogenesis. In the present
      study, pregnant vitamin A-deficient (VAD) rats were maintained during early
      pregnancy on the short half-life vitamin A metabolite, all-trans retinoic acid
      (atRA), in an amount sufficient to support normal development to E10.5, with a
      higher level of atRA (250 microg atRA/g diet) provided from embryonic day (E) 8.5
      10.5 to prevent mid-gestational resorption. When limiting amounts of atRA (1.5 or
      12 microg/g diet) were provided after E10.5, a highly reproducible and penetrant
      state of late fetal vitamin A deficiency (late VAD) was induced in the organs of
      developing fetuses. In addition, late VAD fetuses displayed both anteriorization
      of cervical regions and novel posteriorization events at the thoracic and sacral
      levels of the skeleton, and showed sternal and pelvic malformations not
      previously observed in early VAD or genetic models. The expression of several Hox
      genes (Hoxd3 and Hoxb4) was altered in late VAD embryos, with a reduction in
      Hoxd3 noted as early as 1 day after instituting deficiency. All late VAD-induced
      malformations were prevented by the addition of retinol starting at E10.5,
      whereas provision of a high level of atRA throughout pregnancy improved but could
      not completely rescue the development of all organ systems. This work defines a
      nutritional model in which vitamin A deficiency can be induced during fetal
      development, and reveals new functions for the vitamin in the development of the
      axial and appendicular skeleton.

PMID- 18321480
TI  - Near complete loss of retinal ganglion cells in the math5/brn3b double knockout
      elicits severe reductions of other cell types during retinal development.
AB  - Retinal ganglion cells (RGCs) are the first cell type to differentiate during
      retinal histogenesis. It has been postulated that specified RGCs subsequently
      influence the number and fate of the remaining progenitors to produce the rest of
      the retinal cell types. However, several genetic knockout models have argued
      against this developmental role for RGCs. Although it is known that RGCs secrete
      cellular factors implicated in cell proliferation, survival, and differentiation,
      until now, limited publications have shown that reductions in the RGC number
      cause significant changes in these processes. In this study, we observed that
      Math5 and Brn3b double null mice exhibited over a 99% reduction in the number of
      RGCs during development. This severe reduction of RGCs is accompanied by a
      drastic loss in the number of all other retinal cell types that was never seen
      before. Unlike Brn3b null or Math5 null animals, mice null for both alleles lack
      an optic nerve and have severe retinal dysfunction. Results of this study support
      the hypothesis that RGCs play a pivotal role in the late phase of mammalian
      retina development.

PMID- 18321481
TI  - Mercury as a serious health hazard for children in gold mining areas.
AB  - In many developing countries, mercury is used to extract gold from ore in small
      scale mining areas. Exposure through mercury in these small-scale mining
      communities is a serious health hazard, especially to the children living and
      working there. Many children begin working with immediate contact to mercury from
      the very early age of seven. In Indonesia and Zimbabwe, 166 children were
      clinically examined for mercury. The mercury concentration in the blood, urine,
      and hair was analyzed. Compared to the control groups, the exposed children
      showed typical symptoms of mercury intoxication, such as ataxia. The children
      working with mercury had high levels of this substance in the various
      biomonitors. The exposure derives mainly from the liquid mercury used to bind
      gold, forming an amalgam. The amalgam is heated and the smelting amalgam releases
      mercury vapor plus the wanted gold. Mercury vapor in contrast to liquid mercury
      is highly toxic. This elemental, vaporized mercury is the main form of exposure.
      Since in over 50 countries children live in small-scale gold mining areas and are
      exposed in a similar way to mercury, immediate action is needed to reduce this
      severe chemical health hazard for children. Child labor with hazardous substances
      such as mercury must be stopped.

PMID- 18321482
TI  - Effect of pregnane X receptor ligands on transport mediated by human OATP1B1 and
      OATP1B3.
AB  - The pregnane X receptor is a ligand-activated transcription factor that is
      abundantly expressed in hepatocytes. Numerous drugs are pregnane X receptor
      ligands. To bind to their receptor they must cross the sinusoidal membrane.
      Organic anion transporting polypeptides 1B1 and 1B3 (OATP1B1 and OATP1B3) are
      polyspecific transporters expressed at the sinusoidal membrane of human
      hepatocytes. They mediate transport of a variety of drugs including the pregnane
      X receptor ligands rifampicin and dexamethasone. To test whether additional
      pregnane X receptor ligands interact with OATP1B1- and 1B3-mediated transport, we
      developed Chinese Hamster Ovary (CHO) cell lines stably expressing OATP1B1 or 1B3
      at high levels. OATP1B1- and 1B3-mediated estradiol-17beta-glucuronide uptake was
      inhibited by several pregnane X receptor ligands in a concentration dependent
      way. IC(50) values for rifampicin, paclitaxel, mifepristone, and troglitazone
      were within their respective pharmacological free plasma concentrations. Kinetic
      analysis revealed that clotrimazole inhibits OATP1B1-mediated estradiol-17beta
      glucuronide transport with a K(i) of 7.7+/-0.3 microM in a competitive way.
      However, uptake of OATP1B3-mediated estradiol-17beta-glucuronide was stimulated
      and this stimulation was due to an increased apparent affinity. Transport of
      estrone-3-sulfate was hardly affected while all other substrates tested were
      inhibited. Additional azoles like fluconazole, ketoconazole and miconazole did
      not stimulate OATP1B3-mediated estradiol-17beta-glucuronide transport. In
      summary, these results demonstrate that pregnane X receptor ligands, by
      inhibiting or stimulating OATP-mediated uptake, can lead to drug-drug
      interactions at the transporter level.

PMID- 18321483
TI  - Corticosteroid receptor polymorphisms: determinants of vulnerability and
      resilience.
AB  - Why some individuals thrive and others break down under similar adverse
      conditions, is a central question in the neuroendocrinology of stress related
      psychopathology. The brain mineralocorticoid (MR) and glucocorticoid receptors
      (GR) operate in balance to coordinate behavioural, autonomic and neuroendocrine
      response patterns involved in homeostasis and health. Genetic variants of both
      the MR and GR have been functionally characterized. The four GR-gene single
      nucleotide polymorphisms (SNPs) (ER22/23EK (allele frequency: 3%), N363S (4%),
      BclI (37%), A3669G (15%)) and the two MR-gene SNPs (-2 G/C (50%), MR-I180V (11%))
      showed in vitro changes in transactivational capacity, or affect stability of the
      mRNA (GR exon 9beta A3669G). All of these MR-and GR-SNPs change the regulation of
      the hypothalamus-pituitary-adrenal (HPA) axis at different levels including basal
      level (-2 G/C), dexamethasone induced negative feedback (ER22/23EK, N363S, BclI,
      9beta A3669G) or following a psychosocial stress test (Trier Social Stress Test
      (TSST); all of the MR-and GR-SNPs). Importantly, the MR-I180V increased autonomic
      output and enhanced cortisol secretion during the TSST. Recently, several of
      these MR-and GR-variants have been found associated with psychopathology
      (depression, bipolar disorder). These data provide evidence that dysregulation of
      MR and GR are causative in the pathogenesis of depression and that these MR-and
      GR-gene variants are part of the genetic make up that determines individual
      stress-responsivity and coping style, affecting vulnerability to disease.

PMID- 18321484
TI  - Continuous delivery of ropinirole reverses motor deficits without dyskinesia
      induction in MPTP-treated common marmosets.
AB  - L-DOPA treatment of Parkinson's disease induces a high incidence of motor
      complications, notably dyskinesia. Longer acting dopamine agonists, e.g.
      ropinirole, are thought to produce more continuous dopaminergic stimulation and
      less severe dyskinesia. However, standard oral administration of dopamine
      agonists does not result in constant plasma drug levels, therefore, more
      continuous drug delivery may result in both prolonged reversal of motor deficits
      and reduced levels of dyskinesia. Therefore, we compared the effects of repeated
      oral administration of ropinirole to constant subcutaneous infusion in MPTP
      treated common marmosets. Animals received oral administration (0.4 mg/kg, BID)
      or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14
      days (Phase I). The treatments were then switched and continued for a further 14
      days (Phase II). In Phase I, locomotor activity was similar between treatment
      groups but reversal of motor disability was more pronounced in animals receiving
      continuous infusion. Dyskinesia intensity was low in both groups however there
      was a trend suggestive of less marked dyskinesia in those animals receiving
      continuous infusion. In Phase II, increased locomotor activity was maintained but
      animals switched from oral to continuous treatment showing an initial period of
      enhanced locomotor activity. The reversal of motor disability was maintained in
      both groups, however, motor disability tended towards greater improvement
      following continuous infusion. Importantly, dyskinesia remained low in both
      groups suggesting that constant delivery of ropinirole neither leads to priming
      nor expression of dyskinesia. These results suggest that a once-daily controlled
      release formulation may provide improvements over existing benefits with standard
      oral ropinirole in Parkinson's disease patients.

PMID- 18321485
TI  - Eimeria stiedae: experimental infection in rabbits and the effect of treatment
      with toltrazuril and ivermectin.
AB  - The aim of this study was to investigate the clinical, haematological,
      biochemical, lipid peroxidation, ultrasonographic and pathologic findings in
      hepatic coccidiosis induced by Eimeria stiedae in rabbits, and also to compare
      the treatment effects of both toltrazuril and ivermectin separately and in
      combination. In this study, 56 rabbits were divided into eight groups. The first
      group was designated as healthy control group. Rabbits were infected with 40.000
      sporulated oocysts of E. stiedae. Groups 2, 3, 4, 5, 6, 7 and 8 were allocated as
      the infected control group, infected+toltrazuril-treated group,
      infected+ivermectin-treated group, infected+toltrazuril+ivermectin-treated group,
      non-infected+toltrazuril-treated group, non-infected+ivermectin-treated group,
      non-infected+toltrazuril+ivermectin-treated group, respectively. Haematocrit,
      Haemoglobin and MCV values as well as percentage of lymphocyte decreased in
      Groups 2 and 4 whereas leucocyte counts and percentage of granulocyte leucocyte
      increased. Serum GGT, ALT and AST activities increased but albumin value
      decreased. Plasma MDA concentrations increased whereas erythrocyte CAT, GSH-Px,
      and SOD activities decreased. Mean oocyst numbers in per gram faeces (epg values)
      increased in both groups during the study. Ultrasonographic examination revealed
      that the liver was enlarged and had hyperechogenic parenchyma. Bile ducts were
      dilated and hyperechogenic and the gall bladder was dilated. The livers of these
      animals were enlarged and typical macroscopic and microscopic findings of
      coccidiosis were present. Treatment with toltrazuril and toltrazuril+ivermectin
      combination were highly effective in reducing faecal oocyst output in infected
      rabbits. Haematological, biochemical and lipid peroxidation parameters and,
      ultrasonographic findings of the liver were close to control values for Groups 3
      and 5. Necropsy of these animals showed no visible lesions related to hepatic
      coccidiosis although a few oocysts were detected in the bile duct epithelial
      cells.

PMID- 18321486
TI  - Comparison of clomiphene citrate, metformin, or the combination of both for first
      line ovulation induction, achievement of pregnancy, and live birth in Asian women
      with polycystic ovary syndrome: a randomized controlled trial.
AB  - OBJECTIVE: To determine the first-line medication to be used in anovulatory
      patients with polycystic ovary syndrome (PCOS) for ovulation induction and
      pregnancy achievement. DESIGN: Randomized controlled trial. SETTING: Infertility
      unit of a public hospital. PATIENT(S): One hundred fifteen newly diagnosed
      patients with PCOS based on ESHRE/ASRM criteria. INTERVENTION(S): These patients
      were assigned to three groups: group 1 (38 patients) received 500 mg of metformin
      three times a day; group 2 (39 patients) received clomiphene citrate (CC) at an
      incremental dose; group 3 (38 patients) received both medications. MAIN OUTCOME
      MEASURE(S): Rates of ovulation, pregnancy (PR), and live birth. RESULT(S): The
      ovulation rate was 23.7% in the metformin group, 59% in the CC group, and 68.4%
      in the combination treatment group. This was translated into a similar PR and
      live birth rate, which were higher in the CC and combination groups compared to
      the metformin group (PR: 7.9%, 15.4%, and 21.1%; live birth rate: 7.9%, 15.4%,
      and 18.4% in metformin, CC, and combination treatment groups, respectively),
      although statistically the differences were not significant. There were no
      multiple pregnancies and the rate of spontaneous first trimester loss was similar
      to the general population. CONCLUSION(S): Clomiphene citrate should be the first
      line treatment for ovulation induction in anovulatory patients with PCOS.

PMID- 18321487
TI  - Follicle-stimulating hormone receptor polymorphism (Thr307Ala) is associated with
      variable ovarian response and ovarian hyperstimulation syndrome in Indian women.
AB  - OBJECTIVE: To evaluate the association of FSH receptor polymorphism and ovarian
      response. DESIGN: Retrospective study. SETTING: Academic research institute and
      private IVF clinic. PATIENT(S): Fifty women were recruited in an assisted
      reproductive technology program (ART) and 100 proven fertile women of Indian
      origin. INTERVENTION(S): Polymerase chain reaction, restriction fragment-length
      polymorphism for detecting polymorphisms at T(307)A and N(680)S. MAIN OUTCOME
      MEASURE(S): FSH receptor polymorphisms, serum FSH, and estradiol levels, amount
      of FSH administered, occurrence of ovarian hyperstimulation syndrome (OHSS).
      RESULT(S): Prevalence of polymorphism at 307 position was 24%, 53%, and 23% in
      controls and 24%, 62%, and 14% in ART subjects for TT, TA, and AA, respectively,
      whereas at position 680, it was 31%, 56%, and 13% in controls and 42%, 46%, and
      12% in ART subjects for NN, NS, and SS, respectively. The amount of FSH required
      for ovulation induction was low in AA compared with TT and TA subjects; the
      estradiol levels before and on the day of hCG administration were significantly
      higher. Eighty-five percent of the subjects with AA genotype developed OHSS.
      CONCLUSION(S): In Indian women, the subjects with AA genotype require low amounts
      of FSH for ovarian stimulation and have an increased risk of developing OHSS.

PMID- 18321488
TI  - P27Kip1 is down-regulated in the endometrium of women with endometriosis.
AB  - OBJECTIVE: To evaluate p27 protein expression in the endometrium of women with
      endometriosis. DESIGN: Transversal case-control study. SETTING: Endometriosis
      Unit, Federal University of Sao Paulo, Brazil. PATIENT(S): Thirteen patients with
      stage I/II endometriosis, five with stage III/IV endometriosis, and 11 control
      subjects. INTERVENTION(S): Endometrial biopsies were obtained from patients with
      proven endometriosis and women without disease at laparoscopy. P27 protein was
      immunolocalized in the biopsy tissues and quantified by light microscopy. MAIN
      OUTCOME MEASURE(S): Immunostaining scores of glandular and stromal cells in
      endometrial biopsies obtained from patients with confirmed endometriosis compared
      with those of healthy control women with normal pelvis at laparoscopy. The
      staining scores of stage I/II and stage III/IV patients and of both patient
      groups and the control group were compared. RESULT(S): The level of p27 protein
      expression observed in the control group, both in the stroma and in the
      endometrial glands, was significantly different from that observed in the
      endometriosis patient groups. Significant differences in p27 protein expression
      levels in the glandular epithelium and stroma were not observed among groups of
      patients with endometriosis. CONCLUSION(S): The decreased level of p27 protein in
      the endometrium of women with endometriosis suggests that cell cycle alterations
      in the endometrial mucosa may be involved in the pathogenesis of this disease.

PMID- 18321489
TI  - Optimizing the number of cleavage stage embryos to transfer on day 3 in women 38
      years of age and older: a Society for Assisted Reproductive Technology database
      study.
AB  - OBJECTIVE: To determine the optimal number of day 3 embryos to transfer in women
      >or=38 years by conducting an evidence-based evaluation. DESIGN: Retrospective
      analysis of 2000-2004 national SART data. SETTING: National writing group.
      PATIENT(S): A total of 36,103 day 3 embryo transfers in women >or=38 years
      undergoing their first assisted reproductive technology cycle. INTERVENTION(S):
      None. MAIN OUTCOME MEASURE(S): Logistic regression was used to model the
      probability of pregnancy, delivery, and multiple births (twin or high order)
      based on age- and cycle-specific parameters. RESULT(S): Pregnancy rates, delivery
      rates, and multiple rates increased up to transfer of three embryos in 38-year
      olds and four in 39-year-olds; beyond this number, only multiple rates increased.
      In women >or=40 years, delivery rates and multiple rates climbed steadily with
      increasing numbers transferred. Multivariate analysis confirmed the statistically
      significant effect of age, number of oocytes retrieved, and embryo
      cryopreservation on delivery and multiple rates. Maximum FSH level was not an
      independent predictor by multivariate analysis. Use of intracytoplasmic sperm
      injection was associated with lowered delivery rate. CONCLUSION(S): No more than
      three or four embryos should be transferred in 38- and 39-year-olds,
      respectively, whereas up to five embryos could be transferred in >or=40-year
      olds. Numbers of embryos to transfer should be adjusted according to number of
      oocytes retrieved and availability of excess embryos for cryopreservation.

PMID- 18321490
TI  - In vitro fertilization cycle outcome after coasting in gonadotropin-releasing
      hormone (GnRH) agonist versus GnRH antagonist protocols.
AB  - OBJECTIVES: To compare the results of IVF cycles after coasting in patients
      treated with a GnRH antagonist or GnRH agonist protocol. DESIGN: A retrospective
      case-control study. SETTING: Infertility unit in a university-affiliated tertiary
      medical center. PATIENT(S): The study group included all women less than 38 years
      old attending the IVF unit from 2000 to 2006 in whom coasting was used. Data on
      E(2) levels before and after coasting, duration of coasting, number of oocytes
      retrieved and fertilized, embryo quality, moderate-severe ovarian
      hyperstimulation syndrome (OHSS), and pregnancy were collected from the files and
      compared between GnRH agonist (n = 329) and GnRH antagonist (n = 45) cycles.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Number of retrieved oocytes and
      pregnancy rates. RESULT(S): There were no between-group differences in cycle
      parameters. In the antagonist group, there was no need for more than 2 days of
      coasting. There was a significant decrease in the number of retrieved oocytes
      even in short periods of coasting in the antagonist group but not in the agonist
      group. On the day of hCG administration, E(2) levels dropped to a lower level in
      the antagonist cycles. The OHSS rate after coasting was 4.6% in the agonist group
      and 4.4% in the antagonist group. Corresponding pregnancy rates after coasting
      were 27.4% and 24.4%. CONCLUSION(S): The same criteria for coasting can be
      applied in GnRH agonist as in GnRH antagonist cycles, with a similar IVF result.

PMID- 18321491
TI  - Altered vascular endothelial growth factor expression during GnRH antagonist
      protocol in women of reproductive age with normal baseline hormone profiles.
AB  - OBJECTIVE: To explain the unexpected low response to GnRH antagonist protocol in
      reproductive women with normal baseline hormone profiles. DESIGN: Retrospective
      study. SETTING: University hospital. PATIENT(S): Twenty-five women undergoing
      their first IVF cycle. INTERVENTION(S): Follicular fluid (FF) from large
      follicles (>15 mm) was obtained during oocyte retrieval from unexpected low
      responders (n = 13, group A) and 12 age-matched normal responders (n = 12, group
      B). MAIN OUTCOME MEASURE(S): The FF markers known to reflect follicle environment
      (insulin-like growth factor [IGF] II, IGF-binding protein 4, mullerian-inhibiting
      substance, pregnancy-associated plasma protein A, soluble Fas, and vascular
      endothelial growth factor [VEGF]) were analyzed by ELISA. RESULT(S): The baseline
      characteristics (age, day 3 serum LH, FSH, E(2), duration and dose of r-FSH, GnRH
      antagonist) were not different between the two groups. The number of large
      follicles, oocytes retrieved, and serum E(2) levels on the day of hCG injection
      were significantly higher in group B. Whereas the other follicular markers did
      not differ between the two groups, VEGF was significantly higher in group A. In
      addition, the VEGF concentration showed an inverse correlation with the total
      number of oocytes retrieved. CONCLUSION(S): The unexpected low response in women
      with normal basal hormone profiles, during GnRH antagonist protocol, was
      associated with altered follicular VEGF expression.

PMID- 18321492
TI  - Recanalization and particle exclusion after embolization of uterine arteries in
      sheep: a long-term study.
AB  - OBJECTIVE: To compare the long-term evolution of uterine arteries after
      embolization with the two most commonly used embolic agents for fibroid
      embolization: nonspherical polyvinyl alcohol (PVA) particles and trisacryl
      gelatin microspheres (TGMS). DESIGN: Prospective study. SETTING: University-based
      interventional radiology, pathology, and reproductive physiology units.
      ANIMAL(S): Two groups of 10 sheep embolized in the uterine artery.
      INTERVENTION(S): Embolization of the uterine artery with either 600-1000 microm
      nonspherical polyvinyl alcohol (PVA) particles or with 700-900 microm trisacryl
      gelatin microspheres (TGMS). Animals were synchronized and naturally inseminated.
      Animals were killed at 26 months. MAIN OUTCOME MEASURE(S): Uteri were examined
      pathologically for vessel size, site of occlusion, recanalization rate of
      vessels, and particle location within the vascular wall. RESULT(S): The PVA
      particles were more numerous in the vessels' lumen than the TGMS particles (13.3
      +/- 20.8 vs. 2.5 +/- 2.7), were located more proximally than TGMS (97% vs. 68% in
      the trunk and first branches of the uterine artery), and were found almost
      exclusively in the intima (99.2%). In contrast, 54.4% of the TGMS particles were
      found in the intima, and 45.6% partially or totally excluded. The rate of
      recanalization was not statistically significantly different for PVA and TGMS
      (65.2% vs. 60.6%). CONCLUSION(S): The long-term evolution of uterine arteries was
      different after uterine artery embolization with PVA and TGMS because PVA
      particles formed large-sized aggregates that occluded proximal vessels and
      remained in the vessel intima. Microspheres occluded more distal vessels, and
      about 50% of them were partially or totally excluded from the vessel.

PMID- 18321493
TI  - The role of antimullerian hormone in prediction of outcome after IVF: comparison
      with the antral follicle count.
AB  - OBJECTIVE: To assess the value of antimullerian hormone (AMH) as a test to
      predict poor ovarian response and pregnancy occurrence after IVF and to compare
      it with the performance of the antral follicle count (AFC). DESIGN: A systematic
      review of existing literature and a meta-analysis were carried out. After a
      comprehensive search, studies were included if 2 x 2 tables for outcomes poor
      response and pregnancy in IVF patients in relation to AMH or AFC could be
      constructed. SETTING: Academic referral center for tertiary care. PATIENT(S):
      Cases indicated for IVF. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Poor
      response and nonpregnancy after IVF. RESULT(S): A total of 13 studies were found
      reporting on AMH and 17 on AFC. Because of heterogeneity among studies,
      calculation of a summary point estimate for sensitivity and specificity was not
      possible. However, for both tests summary receiver operating characteristic
      curves for the outcome measures poor response and nonpregnancy could be estimated
      and compared. The curves for the prediction of poor response indicated no
      significant difference between the performances of AMH and AFC. For the
      prediction of nonpregnancy, poor performance for both AMH and AFC was found.
      CONCLUSION(S): In this meta-analysis it was shown that AMH has at least the same
      level of accuracy and clinical value for the prediction of poor response and
      nonpregnancy as AFC.

PMID- 18321494
TI  - New media for culture to blastocyst.
AB  - OBJECTIVE: To develop sequential media for extended culture of embryos in human
      IVF, with use of a mouse embryo assay. The BlastAssist system was developed.
      Blastocyst culture has been our routine method since 1994, using earlier media
      IVF and M3 in sequence. DESIGN: Experimental laboratory study. SETTING:
      University Hospital and university research unit. ANIMAL(S): F1 hybrids between
      CD1 female and BDF male mice. INTERVENTION(S): Two-cell mouse embryos were
      cultured 4 days in test media; 1 day in phase 1 medium followed by 3 days in
      phase 2 medium. MAIN OUTCOME MEASURE(S): Percentage of expanded and hatched
      blastocysts. RESULT(S): Compared with a two-cell block in the old culture system,
      more than 80% went to the blastocyst stage in the new media. The new medium
      system was based on a heavily modified low-glucose Earle's balanced salt
      solution. Additions were pyruvate, lactate, amino acids, human serum albumin, and
      Synthetic Serum Replacement. In contrast to regular tissue culture cells, embryos
      required an increased concentration of EDTA. The final media produced a
      blastocyst frequency of 94% and a day 4 hatching frequency of 71%. CONCLUSION(S):
      With the high blastocyst frequency demonstrated here, the combination of
      blastocyst culture and single ET should be an effective means of treatment in
      patients and could help to eliminate multiple gestations. The BlastAssist system
      is commercially available.

PMID- 18321495
TI  - Impact of insulin resistance on the developmental potential of immature oocytes
      retrieved from human chorionic gonadotropin-primed women with polycystic ovary
      syndrome undergoing in vitro maturation.
AB  - In a homeostasis model assessment-insulin resistance (HOMA-IR)-positive group of
      women with polycystic ovary syndrome undergoing in vitro maturation (IVM), the
      maturation rate of immature oocytes was significantly lower compared with a HOMA
      IR negative group of women (47% vs. 59%). The results of our study showed that IR
      and hyperinsulinemia have an adverse effect on the developmental potential of
      immature oocytes retrieved in the IVM procedure.

PMID- 18321496
TI  - In vitro-matured rat oocytes have low mitochondrial deoxyribonucleic acid and
      adenosine triphosphate contents and have abnormal mitochondrial redistribution.
AB  - OBJECTIVE: To study the development and function of mitochondria in in vitro
      matured rat oocytes derived from follicles of different sizes. DESIGN:
      Experimental animal study. SETTING: Department of Anatomy at the University of
      Hong Kong. ANIMAL(S): Immature female Sprague-Dawley rats that were 25 days of
      age. INTERVENTION(S): Immature oocytes were collected from rat ovarian follicles
      of different sizes and were induced to mature in vitro. MAIN OUTCOME MEASURE(S):
      The number of copies of mitochondrial DNA, mitochondrial activity, adenosine
      triphosphate content of matured oocytes, and rates of fertilization and
      blastulation were determined. RESULT(S): The mitochondrial DNA copy number of
      oocytes increased linearly with the diameter of antral follicles. The
      mitochondrial DNA copy number, adenosine triphosphate content, and proportion of
      oocytes with peripheral distribution of mitochondria in in vitro-matured oocytes
      from small antral follicles were significantly lower than those from preovulatory
      follicles and in vivo-matured oocytes. Compared with in vitro-matured oocytes
      from small antral follicles, those from preovulatory follicles and in vivo
      matured oocytes also had significantly better fertilization potential and higher
      blastulation rate. CONCLUSION(S): The inferior developmental potential of in
      vitro-matured oocytes may be attributed partly to a reduced number of
      mitochondria, resulting in insufficient production of adenosine triphosphate for
      required developmental events.

PMID- 18321497
TI  - Serum inhibin B and anti-Mullerian hormone are not superior to follicle
      stimulating hormone as predictors of the presence of sperm in testicular fine
      needle aspiration in men with azoospermia.
AB  - OBJECTIVE: To compare FSH, inhibin B (INHB), and anti-Mullerian hormone (AMH) as
      predictors of the recovery of sperm in testicular fine-needle aspiration biopsy
      (FNA) performed in men with azoospermia. DESIGN: Cross-sectional, clinical study.
      SETTING: Academic Unit of Reproductive Endocrinology. PATIENT(S): Fifty-one men
      with azoospermia and 31 controls. INTERVENTION(S): Testicular FNA. MAIN OUTCOME
      MEASURE(S): Serum FSH, INHB, and AMH levels. RESULT(S): Clinical diagnoses in men
      with azoospermia were idiopathic nonobstructive azoospermia (n = 34, 67%),
      cryptorchidism (n = 4, 8%), varicocele (n = 3, 6%), and other diagnoses (n = 10,
      16%). In pairwise comparison of receiver operating characteristic curves, none of
      FSH (area under curve 0.716), INHB (0.610), AMH (0.565), or volume of the larger
      testis (0.693) was proved to be superior to the others as predictor of sperm
      retrieval during an FNA procedure. Similarly, in a logistic regression analysis,
      none of FSH, AMH, INHB, or volume of the larger testis could predict presence of
      sperm in FNA. CONCLUSION(S): Serum INHB and AMH, as well as their combination,
      are not superior to FSH as predictors of the presence of sperm in testicular FNA
      in men with azoospermia and should not be used for this purpose.

PMID- 18321498
TI  - Androgen receptor is expressed in both X- and Y-carrier human spermatozoa.
AB  - OBJECTIVE: To quantify the amount of AR messenger RNA (mRNA) and to analyze the
      presence and functionality of the AR protein in X- and Y-carrier human
      spermatozoa. DESIGN: A molecular and cellular research study. SETTING: Academic
      research clinic and laboratories. PATIENT(S): Ten normozoospermic volunteers.
      INTERVENTION(S): Sperm were analyzed for expression of AR mRNA and protein. The
      functionality of AR protein was assessed after incubation with 1 nM of synthetic
      androgen. MAIN OUTCOME MEASURE(S): Reverse-transcription polymerase chain
      reaction (PCR), real-time PCR, Western immunoblotting, confocal
      immunofluorescence, and fluorescence in situ hybridization analysis were
      performed. RESULT(S): A significant amount of AR mRNA (around 30% of that found
      in the testis) was found in sperm. Androgen receptor protein was found in both X-
      and Y-carrier spermatozoa and translocates into the nucleus in the presence of
      synthetic androgen. CONCLUSION(S): A functional AR is expressed in human sperm.
      In view of the fact that AR protein is found in both X- and Y-carrier
      spermatozoa, it most probably is translated in earlier steps of spermatogenesis
      and moves to Y-carrier spermatids through the cytoplasmic bridges.

PMID- 18321499
TI  - Racial differences in self-reported infertility and risk factors for infertility
      in a cohort of black and white women: the CARDIA Women's Study.
AB  - OBJECTIVE: To determine racial differences in self-reported infertility and in
      risk factors for infertility in a cohort of black and white women. DESIGN: A
      cross-sectional analysis of data from the longitudinal Coronary Artery Risk
      Development in Young Adults (CARDIA) Study, a prospective, epidemiologic
      investigation of the determinants and evolution of cardiovascular risk factors
      among black and white young adults and from the ancillary CARDIA Women's Study
      (CWS). SETTING: Population-based sample from four US communities (Birmingham, AL;
      Chicago, IL; Minneapolis, MN; Oakland, CA). PATIENT(S): Women aged 33-44 years
      who had complete data (n = 764). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S):
      Self-report of ever having unprotected sexual intercourse for at least 12 months
      without becoming pregnant. RESULT(S): Among nonsurgically sterile women, blacks
      had a twofold increased odds (95% confidence interval [CI] 1.3-3.1) of
      infertility compared with whites after adjustment for socioeconomic position
      (education and ability to pay for basics), correlates of pregnancy intent
      (marital status and hormonal contraceptive use), and risk factors for infertility
      (age, smoking, T, fibroid presence, and ovarian volume). The corresponding odds
      ratio among all women was 1.5 (95% CI 1.0-2.2). Difficulty paying for basics and
      ovarian volume were associated with infertility among black but not white women.
      CONCLUSION(S): In this population-based sample, black women were more likely to
      have experienced infertility. This disparity is not explained by common risk
      factors for infertility, such as smoking and obesity, and among nonsurgically
      sterile women, it is not explained by gynecologic risk factors such as fibroids
      and ovarian volume.

PMID- 18321500
TI  - Infertility knowledge and attitudes in urban high school students.
AB  - OBJECTIVE: To assess knowledge and attitudes about infertility through a survey.
      DESIGN: Descriptive study with stratified random sampling. SETTING: Eighteen high
      schools were selected in Toronto, Ontario, Canada. PATIENT(S): Seven hundred
      seventy-two students participated in the study. The mean age of students was 17.5
      +/- 0.98 years. Females were 49.02% (n = 377) of the sample. The sample was
      ethnically diverse, consisting of >13 groups. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): The main outcome was infertility knowledge and attitudes. Secondary
      analysis compared gender and socioeconomic status. RESULT(S): The majority (608;
      79%) of high school students were familiar with the term infertility (95%
      confidence interval: 76%, 82%). More than 94% did not know that chlamydia or
      gonorrhea could lead to infertility. Seventy percent felt that protecting their
      fertility was important to them, with significantly more females feeling this
      way. There was a higher proportion of students from schools with low
      socioeconomic status who gave incorrect answers to knowledge-related questions
      and were unaware of the association between sexually transmitted infections and
      infertility. CONCLUSION(S): Although the majority of students value their
      fertility, knowledge about preventable factors causing infertility was limited.
      Increased efforts are needed to educate students on factors that may affect their
      fertility.

PMID- 18321501
TI  - Premature ovarian failure and dehydroepiandrosterone.
AB  - Since the first successful birth at our center following treatment with DHEA in a
      patient with premature ovarian failure (POF), all subsequent patients with POF
      underwent the same treatment protocol. Receiving very encouraging results (FSH
      level was decreased in the first five patients and all achieved pregnancy), it
      was decided to study the action of DHEA for a reasonable length of time and in a
      larger number of patients to confirm the effectiveness of this particular
      therapeutic regime.

PMID- 18321502
TI  - Discovery of four estrogen receptors and their expression profiles during testis
      recrudescence in male Spinibarbus denticulatus.
AB  - Estrogen plays an important role in male reproduction. Most of the actions are
      mediated by estrogen receptor (ER). To investigate the profile of estrogen
      affecting male fertility, we firstly cloned four ERs from the male Spinibarbus
      denticulatus, a local economically important cyprinid fish in China. Phylogenetic
      tree analysis ranked the four sdERs as two distinct groups of ERalpha and beta,
      which could be further divided into duplicated isoforms 1 and 2, respectively.
      High score identities were shared between each of the duplicated isoforms. All of
      the four sdERs distributed in central nervous system of male fish with a quite
      broad spectrum. However, distribution diversity became evident between sdERalpha
      and sdERbeta subtypes in the peripheral tissues. Both of the two isoforms of
      ERbeta were detected in all seven tissues examined, while expression of
      sdERalpha1 was mainly limited to liver, kidney, testis and intestine and
      sdERalpha2 was confined to liver, heart, kidney, testis and gill. During the
      testis recrudescing stages, serum concentration of luteinizing hormone (LH),
      testosterone (T) and estradiol-17beta (E(2)) were increasing. T and LH levels in
      the circulation were high until the later fully recrudesced phase, while serum
      E(2) level was low all the time. Quantitative real-time RT-PCR analysis
      determined the most abundance of sdERs in pituitary where the two sdERalpha
      isoforms positively expressed with testis development, while sdERbeta isoforms
      expressed with a reverse pattern. sdERalpha1 and sdERbeta1 were the primary forms
      in testis. sdERalpha1 gradually increased during the recrudescence process while
      sdERbeta1 firstly decreased during the recrudescing stage and then positively
      expressed in fully recrudesced stage. Little or no signal was detected in brain.
      The present work provided evidence of four sdERs in male reproductive system and
      suggested an important role of sdERalpha1 during testis recrudescence. Pituitary
      contained duplicates forms of sdERalpha which may play a role in the feedback
      effects of estrogen on LH secretion.

PMID- 18321503
TI  - Identification of putative crustacean neuropeptides using in silico analyses of
      publicly accessible expressed sequence tags.
AB  - The development of expressed sequence tags (ESTs) for crustacean cDNA libraries
      and their deposition in publicly accessible databases has generated a rich
      resource for peptide discovery in this commercially and ecologically important
      arthropod subphylum. Here, we have conducted in silico searches of these
      databases for unannotated ESTs encoding putative neuropeptide precursors using
      the BLAST program tblastn, and have predicted the mature forms of the peptides
      encoded by them. The primary strategy used was to query the database with known
      decapod prepro-hormone sequences or, in some instances, insect precursor protein
      sequences. For neuropeptides for which no prepro-hormones are known, the peptides
      themselves were used as queries. For those peptides expected to originate from a
      common precursor, the individual sequences were combined, with each peptide
      flanked by a dibasic processing site and, if amidated, a glycine residue. Using
      these approaches, 13 unannotated ESTs encoding putative neuropeptide precursors
      were found. For example, using the first strategy, putative Marsupenaeus
      japonicus prepro-hormones encoding B-type allatostatins, neuropeptide F (NPF),
      and orcokinins were identified. Similarly, several Homarus americanus ESTs
      encoding putative orcokinin precursors were found. In addition to the decapod
      prepro-hormones, ESTs putatively encoding a NPF isoform and a red pigment
      concentrating hormone-like peptide were identified from the cladoceran Daphnia
      magna, as was one EST putatively encoding multiple tachykinin-related peptides
      from the isopod Eurydice pulchra. Using the second strategy, we identified a
      Carcinus maenas EST encoding HIGSLYRamide, a peptide recently discovered via mass
      spectrometry from Cancer productus. Using mass spectral methods we confirmed that
      this peptide is also present in Carcinus maenas. Collectively over 50 novel
      crustacean peptides were predicted from the identified ESTs, providing a strong
      foundation for future investigations of the evolution, regulation and function of
      these and related molecules in this arthropod taxon.

PMID- 18321504
TI  - Female-enriched expression of ERalpha during gonad differentiation of the urodele
      amphibian Pleurodeles waltl.
AB  - In the amphibian Pleurodeles waltl, estradiol treatment of genetically male
      larvae (ZZ) induces male-to-female sex reversal whereas heat treatment of
      genetically female larvae (ZW) inhibits estradiol synthesis and leads to female
      to-male sex reversal. No data are available on estrogen receptors in this
      species. In the present study, we have isolated a unique full-length pwERalpha
      cDNA and its 5'-flanking region whose promoter activity was confirmed by
      transfection assays. RT-PCR studies performed in adult animals using ERalpha
      specific primers, revealed that pwERalpha mRNA was present mainly in reproductive
      tissues: gonads, fat body and oviduct. PwERalpha transcript was also detected in
      liver, suggesting its implication in vitellogenesis control as in numerous
      oviparous species. The level of pwERalpha transcripts was also studied during
      gonad differentiation by quantitative real-time PCR. At stage 54(30d) pwERalpha
      expression in gonads of ZW larvae was significantly higher than in ZZ ones. This
      sex-specific discrimination was confirmed when gonad-mesonephros-interrenal
      complexes (GMI), taken at the same stage, were subjected to whole mount in situ
      hybridization. In comparison, the female-enriched expression of P450 aromatase,
      which was studied as a control of ovary differentiation, was observed earlier
      (stage 54). In ZW larvae reared at 32 degrees C, a condition leading to sex
      reversal, pwERalpha mRNA level at stage 54(30d) was lower than in control
      females. Taken together, these results showing a female-enriched and
      thermosensitive expression of pwERalpha suggest an important role for this
      receptor in gonad differentiation of the urodele amphibian Pleurodeles waltl.

PMID- 18321505
TI  - Androgen receptor and Kennedy disease/spinal bulbar muscular atrophy.
AB  - Kennedy Disease/Spinal Bulbar Muscular Atrophy (KD/SBMA) is a progressive
      neurodegenerative disease caused by genetic polyglutamine expansion of the
      androgen receptor. We have recently found that overexpression of wildtype
      androgen receptor in skeletal muscle of transgenic mice results in a KD/SBMA
      phenotype. This surprising result challenges the orthodox view that KD/SBMA
      requires expression of polyglutamine expanded androgen receptor within
      motoneurons. Theories relating to the etiology of this disease drawn from studies
      of human patients, cellular and mouse models are considered with a special
      emphasis on potential myogenic contributions to as well as the molecular etiology
      of KD/SBMA.

PMID- 18321506
TI  - Total-body digital X-ray in trauma. An experience report on the first operational
      full body scanner in Europe and its possible role in ATLS.
AB  - When patients enter our emergency room with suspected multiple injuries, Statscan
      provides a full body anterior and lateral image for initial diagnosis, and then
      zooms in on specific smaller areas for a more detailed evaluation. In order to
      examine the possible role of Statscan in the management of multiply injured
      patients we implemented a modified ATLS((R)) algorithm, where X-ray of C-spine,
      chest and pelvis have been replaced by single-total a.p./lat. body radiograph.
      Between 15 October 2006 and 1 February 2007 143 trauma patients (mean ISS 15+/-14
      (3-75)) were included. We compared the time in resuscitation room to 650 patients
      (mean ISS 14+/-14 (3-75)) which were treated between 1 January 2002 and 1 January
      2004 according to conventional ATLS protocol. The total-body scanning time was
      3.5 min (3-6 min) compared to 25.7 (8-48 min) for conventional X-rays, The total
      ER time was unchanged 28.7 min (13-58 min) compared to 29.1 min (15-65 min) using
      conventional plain radiography. In 116/143 patients additional CT scans were
      necessary. In 98/116 full body trauma CT scans were performed. In 18/116 patients
      selective CT scans were ordered based on Statscan findings. In 43/143 additional
      conventional X-rays had to be performed, mainly due to inadequate a.p. views of
      fractured bones. All radiographs were transmitted over the hospital network
      (Picture Archiving and Communication System, PACS) for immediate simultaneous
      viewing at different places. The rapid availability of images for interpretation
      because of their digital nature and the reduced need for repeat exposures because
      of faulty radiography are also felt to be strengths.

PMID- 18321508
TI  - The results of 163 Achilles tendon ruptures treated by a minimally invasive
      surgical technique and functional aftertreatment [Injury 2007;38(7):839-44].

PMID- 18321509
TI  - Less invasive stabilisation system (LISS) for the treatment of periprosthetic
      femoral fractures: a 3-year follow-up.
AB  - Recent publications have reported encouraging results with a locked plating
      system in the management of periprosthetic femoral fractures. However, data on
      mid- or long-term functional outcome is not available. Here we report on the mid
      term functional outcome of 16 patients with a periprosthetic femoral fracture
      following total hip arthroplasty managed with the LISS-system at a 3-year follow
      up. Functional outcome was measured using the Harris Hip score and the Karnofsky
      activity index. The Harris Hip score and the Karnofsky activity index averaged
      79.5 points and 81%, respectively. There were a total of two major complications
      due to screw pullout representing a complication rate of 13%. This series
      suggests that the management of periprosthetic femoral fractures with the LIS
      System results in a good mid-term functional outcome.

PMID- 18321510
TI  - The incidence and characterisation of hospitalised acute spinal trauma in Taiwan-
      a population-based study.
AB  - AIMS: The purpose of this study was to perform a cross-sectional population-based
      study of hospitalised cases due to acute spinal trauma in Taiwan, based on
      information from the nationwide National Health Insurance (NHI) database.
      METHODS: To calculate the annual incidence of hospitalised acute spinal trauma,
      evaluate the distribution of neurological injury and its surgical intervention,
      and analyse the use of medical resources and related factors in Taiwan, the
      entire inpatient datasets were selected between 2000 and 2003 for use in the
      present study. RESULTS: There were 13,371, 13,800, 13,728 and 13,585 cases
      identified in 2000, 2001, 2002 and 2003, respectively, the average incidence of
      hospitalised acute spinal trauma in Taiwan was 61.61/100,000, and it was similar
      in both genders (rate ratio of male to female: 0.99). There was a significant
      trend of increased incidence with increasing age in both genders, particularly
      after the age of 60. The decreasing incidence rate ratios of neurological deficit
      to neurological intactness are 0.75, 0.58, 0.45, 0.26 and 0.16 in the age strata
      of 0-19, 20-39, 40-59, 60-79 and 80 or more years, respectively. In general, the
      operation rate is only 17.3% of all acute spinal injury cases, but it would be up
      to a significant 29.5% if the patients had spinal fractures with neurological
      insufficiency. There is an obvious decreasing trend of operation rate in spinal
      bony trauma with age, but a reverse trend is noted in the group with spinal nerve
      injury without spinal fracture. Finally, the enrolled subjects of acute spinal
      injuries spent $NT 43336.3+/-80270.2 (equal to US$ 1313+/-2432) and stayed for
      8.5+/-8.9 days in hospital. The above two variables of hospitalised medical
      utilisation are significantly different when considering gender, neurological
      status, and surgical intervention or not. Noticeably, if operative treatment for
      acute spinal injury is necessary, the LOS would increase by two times and the
      medical cost by six times. CONCLUSION: In Taiwan, the annual incidence of
      hospitalised acute spinal injuries was higher but the direct cost was much lower.
      The characterisation of gender ratio, neurological condition, and surgical
      performance had been significantly effected by age.

PMID- 18321511
TI  - Epidemiology of spine trauma in an Irish regional trauma unit: a 4-year study.
AB  - Currently there is a lack of information on the full spectrum of spine trauma
      presenting to medical services in a defined geographic area. This study analyses
      the aetiology and demographics of a cohort of spine trauma in the West of
      Ireland. A regional trauma unit has been investigated for a 51-month period. Two
      hundred and eighty-five cases admitted with spine trauma were documented. The
      annual incidence of traumatic spinal injury was 19.54 cases/100,000 persons per
      year. Falls and low-energy trauma are shown to constitute a significant
      proportion of all cases (60.35%). Injury at greater than one level is frequently
      present. The highest peak of injury occurred in the 20-24-year-old age group
      (11.58%). A second peak occurred at 75-79 years of age (7.37%). The commonest
      cause of neurological injury was falls (n=9; 64.3%). This spine trauma register
      has provided valuable insights into the patterns of injury encountered in spine
      trauma patients in this region. It may act as a blueprint for a national spine
      trauma register and highlights the importance of patient education and injury
      prevention strategies.

PMID- 18321512
TI  - The role of electromagnetic stimulation in the management of established non
      union of long bone fractures: what is the evidence?
AB  - BACKGROUND: Non-union following long bone fractures is a cause of significant
      morbidity to the patient. The management of this condition has proved difficult
      for the orthopaedic surgeon. Much research has been carried out on the use of
      electromagnetic stimulation in the healing of non-union. OBJECTIVES: The
      objective of this review is to determine what evidence exists to support
      electromagnetic stimulation in the management of established non-union of long
      bone fractures. METHODS: A systematic search was carried out of the peer-reviewed
      English language literature to identify all studies investigating electromagnetic
      stimulation in the treatment of non-union of fractures of long bones. RESULTS:
      Three of the articles reviewed were randomised clinical trials. Forty-six other
      studies were also included in the review. CONCLUSIONS: There is a consensus that
      electromagnetic stimulation is an effective adjunct to conventional therapy when
      used in the management of non-union of long bone fractures.

PMID- 18321513
TI  - Hemipelvic amputations for recalcitrant pelvic osteomyelitis.
AB  - OBJECTIVE: To evaluate the outcome of recalcitrant deep pelvic infection that
      required a hemipelvic amputation. STUDY DESIGN: Retrospective cohort. SETTING:
      Tertiary referral centre; Level I trauma. PATIENTS: There were 20 patients with
      an infection of the pelvic girdle who developed life-threatening sepsis or had an
      intolerable existence due to putrefied tissues that prevented end of life care.
      All patients failed other more conservative treatments such as limited
      debridement and local wound care. The indication for amputation was life
      threatening sepsis (eight patients), intolerable state with putrid tissue (four
      patients), and both sepsis/putrefaction (eight patients). INTERVENTION: A
      hemipelvic amputation, multidrug antibiotic treatment, and long-term suppression.
      Ten internal hemipelvectomies, eight external hemipelvectomies, and two
      hemicorporectomies were performed. MAIN OUTCOME MEASURE: Survival and recurrence
      of infection. RESULTS: Six patients died within 6 months (mean time 17 weeks,
      range 2-24). The 14 surviving patients had a mean follow-up time of 28 weeks (9
      48). Of these, 10 patients survived with no evidence of ongoing infection, and
      four patients had ongoing infection requiring suppressive antibiotics. All of the
      six deaths were in C-hosts with an average of six comorbidities each; mean age
      was 62 years old. Aetiologies of the infection were vasculopathy (5), spinal cord
      injury (4), post fracture (3), post abdominal surgery (2), gunshot wound (2),
      seeding from bacteraemia (4). Cierny-Mader host class was C (11) and B
      systemic/local (9) with an average of four (4) comorbidities each. Mean estimated
      blood loss=3100 cc and operative time=157 min. There were 11 cases of minor wound
      problems and no flap loss. Pathogens were polymicrobial (16 total pathogens) with
      mean of three per patient (most common was MRSA). Multi-agent antibiotic and
      suppression were used in all patients. In cases with putrefied tissues,
      appropriate nursing care was possible. CONCLUSION: Patients requiring
      hemipelvectomies usually present with sepsis or an intolerable state. Despite
      expected complications, we found that hemipelvectomy is an effective palliative
      tool in selected cases. Age and vascular disease seemed to be associated with
      worse outcomes.

PMID- 18321514
TI  - Severe liver disease in pregnancy.
AB  - OBJECTIVE: To determine the clinical characteristics of patients with fulminant
      hepatitis of pregnancy (FHP) and acute fatty liver of pregnancy (AFLP) and
      analyze their correlation with pregnancy outcome. METHODS: Of 55 pregnant women
      with severe liver disease, 41 had FHP and 14 had AFLP. RESULTS: Jaundice was the
      primary manifestation for both FHP and AFLP and hepatic encephalopathy was the
      most significant complication for both. Disseminated intravascular coagulation,
      albuminuria, and prothrombin activity were found to be independent risk factors
      of maternal mortality for both. However, the rates of preterm labor, fetal
      demise, and neonatal asphyxia were lower in the FHP group. CONCLUSION: Women with
      FHP or AFLP are at risk for severe complications and adverse pregnancy outcome.
      Since the 2 conditions are managed differently, early diagnosis is essential.

PMID- 18321515
TI  - Effects of a psychological intervention on depression in infertile couples.
AB  - OBJECTIVE: To determine factors affecting depression in infertile couples and the
      impact of a psychological intervention before or during infertility treatment.
      METHODS: In a cross-sectional study with 638 infertile couples assessed for
      depression, 140 couples with a member who had a Beck Depression Inventory (BDI)
      score of 17 or higher were randomized to receive psychological treatment either
      before or during infertility treatment. Logistic regression was performed to
      eliminate confounding factors. RESULTS: Depression was initially found in 48% of
      women and 23.8% of men. The mean+/-SD Beck scores fell from 18.7+/-9.7 to 10.7+/
      5.8 (P<0.001) in the group psychologically treated before they received
      infertility treatment. CONCLUSION: The psychological intervention was found
      useful in alleviating depression in infertile couples before they received
      infertility treatment.

PMID- 18321516
TI  - Prevalence of symptoms associated with polycystic ovary syndrome.
AB  - OBJECTIVE: To establish the prevalence of symptoms associated with polycystic
      ovary syndrome (PCOS) in a population-based sample of women from Northern Sweden,
      and to relate symptoms of PCOS to features of metabolic syndrome. METHODS: A
      population-based survey of 147 women under 40 years of age sampled from 267
      eligible women from the Northern Sweden component of the World Health
      Organization's MONICA study. The study involved questionnaires, physical
      examination, and assays of testosterone and sex hormone-binding globulin.
      RESULTS: The estimated prevalence of symptoms associated with PCOS was 4.8% in
      the study population. Features of metabolic syndrome were more common in women
      with signs of hyperandrogenism than in healthy controls. CONCLUSION: The
      estimated prevalence of PCOS in Northern Sweden corresponds with other prevalence
      studies. A simple questionnaire and analysis of the free androgen index are
      sufficient to detect the subgroup with the highest risk for metabolic syndrome.

PMID- 18321517
TI  - Naproxen suppository for perineal pain after vaginal delivery.
AB  - OBJECTIVE: To assess the effectiveness of rectal naproxen for reducing perineal
      pain after vaginal delivery. METHODS: A double-blind randomized controlled trial
      of 142 post partum women randomly allocated to receive either naproxen (71
      patients) or placebo (71 patients) suppositories. The first dose was given
      immediately after complete perineal suturing, while the second dose was given 6
      hours post partum. The validated Thai short-form McGill pain questionnaire was
      used to evaluate perineal pain at 0, 6, and 24 hours post partum. Pain scores
      were analyzed using the unpaired t test. RESULTS: Pain scores at 6 and 24 hours
      for women in the naproxen group were significantly lower compared with women in
      the placebo group (6.4 and 2.3 vs 18.4 and 5.5; P<0.001). No side effects with
      naproxen were found. CONCLUSIONS: Rectal naproxen is effective and safe for
      reducing perineal pain after vaginal delivery.

PMID- 18321518
TI  - Expectation versus reality: a device to illustrate anticipated and perceived pain
      from amniocentesis.

PMID- 18321519
TI  - The influence of medical abortion compared with surgical abortion on subsequent
      pregnancy outcome.
AB  - Seven prospective cohort studies (12484 cases) were included in this review of
      the respective effects on the next pregnancy of medical and surgical abortion in
      early pregnancy. The incidence of miscarriage and postpartum hemorrhage was
      significantly lower in the pregnancy following a medical abortion. No other
      significant differences were found. With respect to the outcome of the next
      pregnancy, first-trimester medical abortions may thus be safer than the surgical
      option.

PMID- 18321520
TI  - The relation of exposure to shift work with atherosclerosis and myocardial
      infarction in a general population.
AB  - OBJECTIVES: We tested the hypothesis that working shifts is related to
      atherosclerosis and myocardial infarction. BACKGROUND: The number of shift
      workers is continuously increasing. Shift work is discussed to be related with
      cardiovascular heart disease. METHODS: A total of 2510 subjects recruited for the
      population-based Study of Health in Pomerania were tested, 698 of whom were
      former shift workers. A general population sample was examined to reach
      generalizibility and to produce results independent from the effects of the
      personal shift schedule and from the specific working conditions. Carotid
      ultrasound was performed to evaluate carotid intima-media thickness. We used
      multivariable analyses to estimate the coronary heart disease risk, adjusted for
      age, sex and atherosclerotic risk factors, stratified by exposure to shift work
      and its duration. RESULTS: Atherosclerotic risk factors differed in part between
      shift workers and non-shift workers. Shift work was associated with
      atherosclerosis and myocardial infarction, depending on the duration of the
      exposure and the age of the participants. Multivariable Cox regression analysis
      identified shift work as a risk factor for myocardial infarction to be manifest
      at younger ages (adjusted hazard ratio 1.53, 95% CI 1.06-2.22). CONCLUSIONS:
      Exposure to shift work is a risk factor for atherosclerosis and myocardial
      infarction. Special prevention programs for shift workers should be provided.

PMID- 18321521
TI  - Solute transport and separation in nanochannel chromatography.
AB  - An analytical model is developed to study the solute transport and separation in
      pressure-driven liquid flow through cylindrical nanochannels. The flow-induced
      streaming potential is found to significantly affect the solute speed, retention
      and dispersion in nanochannel chromatography. These effects are sensitive to the
      solute charge, and found to be mainly dependent on an electrokinetic "figure of
      merit".

PMID- 18321522
TI  - Characterization of a novel pyridinium bromide surface confined ionic liquid
      stationary phase for high-performance liquid chromatography under normal phase
      conditions via linear solvation energy relationships.
AB  - Utilizing linear solvation free energy relationship methodology, a novel
      pyridinium bromide surface confined ionic liquid (SCIL) stationary phase was
      characterized under normal phase high-performance liquid chromatographic
      conditions. A limited set of neutral aromatic probe solutes were utilized to
      rapidly assess the utility of the LSER model, using mobile phases of hexane
      modified with 2-propanol. The excellent correlation of the global fit across the
      mobile phase composition range used in this study for the experimental and
      calculated retention values (R(2)=0.994) indicates that the LSER model is an
      appropriate model of characterizing this polar bonded phase under normal phase
      conditions. For a limited subset of compounds, retention on the pyridinium
      bromide SCIL stationary phase is more highly correlated with that obtained on a
      cyano column than on a diol column under NP conditions.

PMID- 18321523
TI  - Retention of opioids and their glucuronides on a combined zwitterion and
      hydrophilic interaction stationary phase.
AB  - A stationary phase combining zwitterionic ion chromatography and hydrophilic
      interaction chromatography (ZIC-HILIC) from SeQuant was evaluated for the
      chromatography of some opiates and their polar metabolites. The effects of mobile
      phase constitution on retention and resolution were extensively evaluated.
      Different aspects of mobile phase constitution such as ion strength and type of
      buffer, type and amount of organic modifier and pH were examined. The selectivity
      and retention of the opiates compared to their glucuronides could be
      substantially altered with small changes of the mobile phase, especially when the
      type of buffer, i.e., formate or acetate and organic modifier, i.e., acetonitrile
      or methanol were changed. The retention on the ZIC-HILIC was dominated by
      hydrophilic interaction chromatography (HILIC) but considerable effects on the
      selectivity was observed, possibly caused by an ion exchange mechanism due to
      interactions with the charges on the stationary phase.

PMID- 18321524
TI  - Phase behavior and morphology of equimolar mixed cationic-anionic surfactant
      monolayers at the air/water interface: isotherm and Brewster angle microscopy
      analysis.
AB  - The phase behavior and morphological characteristics of monolayers composed of
      equimolar mixed cationic-anionic surfactants at the air/water interface were
      investigated by measurements of surface pressure-area per alkyl chain (pi-A) and
      surface potential-area per alkyl chain (DeltaV-A) isotherms with Brewster angle
      microscope (BAM) observations. Cationic single-alkyl ammonium bromides and
      anionic sodium single-alkyl sulfates with alkyl chain length ranging from C(12)
      to C(16) were used to form mixed surfactant monolayers on the water subphase at
      21 degrees C by a co-spreading approach. The results demonstrated that when the
      monolayers were at states with larger areas per alkyl chain during the monolayer
      compression process, the DeltaV-A isotherms were generally more sensitive than
      the pi-A isotherms to the molecular orientation variations. For the mixed
      monolayer components with longer alkyl chains, a close-packed monolayer with
      condensed monolayer characteristics resulted apparently due to the stronger
      dispersion interaction between the molecules. BAM images also revealed that with
      the increase in the alkyl chain length of the surfactants in the mixed
      monolayers, the condensed/collapse phase formation of the monolayers during the
      interface compression stage became pronounced. In addition, the variations in the
      condensed monolayer morphology of the equimolar mixed cationic-anionic
      surfactants were closely related to the alkyl chain lengths of the components.

PMID- 18321525
TI  - Arsenic speciation in multiple metal environments II. Micro-spectroscopic
      investigation of a CCA contaminated soil.
AB  - The speciation of arsenic (As) in a copper-chromated-arsenate (CCA) contaminated
      soil was investigated using micro-focused X-ray fluorescence (microXRF) and micro
      focused X-ray absorption fine structure (microXAFS) spectroscopies to determine
      if and how the co-contaminating metal cations (Cu, Zn, Cr) influenced the
      speciation of As. 15 microXRF images were collected on 30-mum polished thin
      sections and powder-on-tape samples from which Pearson correlation coefficients
      (rho) between As and various metal species were determined based on the
      fluorescence intensity of each element in each image pixel. 29 microXAFS and two
      bulk-XAFS spectra were collected from depths of 0-20 cm (LM-A) and 20-40 cm (LM
      B) to determine the chemical speciation of As in the soil by target analyses of
      principal components with circa 52 reference spectra and linear least-square
      combination fitting of individual experimental spectra with a refined reference
      phase list (32) of likely As species. Arsenic and metal cations (Cr, Mn, Fe, Cu,
      Zn) accumulated in distinct, isolated areas often not larger than 50 x 50 microm
      in which the Pearson correlation between the elements was strongly positive
      (rho>0.75). The correlation of As to Zn and Cr decreased from >0.9 to <0.8 and
      increased to Cu from approximately 0.6 to >0.8 with depth. Arsenic occurred
      predominantly in the +5 oxidation state. Abstract factor analysis and linear
      least square combination fit analysis suggested that As occurred as a continuum
      of fully and poorly-ordered copper-arsenate precipitates with additional
      components being characterized by surface adsorption complexes on goethite and
      gibbsite in the presence and absence of Zn. Precipitates other than copper-based
      ones, e.g., scorodite, adamite and ojuelaite were also identified. The
      significant co-localization and chemical speciation of As with Cu suggest that
      the speciation of As in a contaminated soils is not solely controlled by surface
      adsorption reactions, but significantly influenced by the co-contaminating metal
      cation fraction. Future studies into As contaminated soil therefore need to focus
      on identifying the speciation of As and the co-localizing metal cations.

PMID- 18321526
TI  - Chemical profiles of mated and virgin queens, egg-laying intermorphs and workers
      of the ant Crematogaster smithi.
AB  - Many colonies of the North American ant Crematogaster smithi contain a "third
      female caste" in addition to queens and workers. These "intermorphs" are
      morphological intermediate of queens and workers and have well-developed ovaries
      but lack a spermatheca for the storage of sperm. They are specialised for laying
      large numbers of unfertilised, viable eggs, most of which serve as food for
      larvae and adults, though a few may eventually develop into males. Based on the
      assumption that cuticular hydrocarbons (CHCs) in social insects honestly signal
      the reproductive status of an individual we investigated the CHC of mated mature
      queens, virgin queens, intermorphs and workers. We expected intermorphs to show
      chemical profiles intermediate between those of mated queens and non-reproductive
      workers. A discriminant analysis of the chemical profiles reliably separated
      queens, virgin queens, and workers, but failed to distinguish between queens and
      intermorphs even though workers were apparently capable of doing so.

PMID- 18321527
TI  - Compensatory and long-range changes in picosecond-nanosecond main-chain dynamics
      upon complex formation: 15N relaxation analysis of the free and bound states of
      the ubiquitin-like domain of human plexin-B1 and the small GTPase Rac1.
AB  - The formation of a complex between Rac1 and the cytoplasmic domain of plexin-B1
      is one of the first documented cases of a direct interaction between a small
      guanosine 5'-triphosphatase (GTPase) and a transmembrane receptor. Structural
      studies have begun to elucidate the role of this interaction for the signal
      transduction mechanism of plexins. Mapping of the Rac1 GTPase surface that
      contacts the Rho GTPase binding domain of plexin-B1 by solution NMR spectroscopy
      confirms the plexin domain as a GTPase effector protein. Regions neighboring the
      GTPase switch I and II regions are also involved in the interaction and there is
      considerable interest to examine the changes in protein dynamics that take place
      upon complex formation. Here we present main-chain nitrogen-15 relaxation
      measurements for the unbound proteins as well as for the Rho GTPase binding
      domain and Rac1 proteins in their complexed state. Derived order parameters, S2,
      show that considerable motions are maintained in the bound state of plexin. In
      fact, some of the changes in S2 on binding appear compensatory, exhibiting
      decreased as well as increased dynamics. Fluctuations in Rac1, already a largely
      rigid protein on the picosecond-nanosecond timescale, are overall diminished, but
      isomerization dynamics in the switch I and II regions of the GTPase are retained
      in the complex and appear to be propagated to the bound plexin domain.
      Remarkably, fluctuations in the GTPase are attenuated at sites, including helices
      alpha6 (the Rho-specific insert helix), alpha7 and alpha8, that are spatially
      distant from the interaction region with plexin. This effect of binding on long
      range dynamics appears to be communicated by hinge sites and by subtle
      conformational changes in the protein. Similar to recent studies on other
      systems, we suggest that dynamical protein features are affected by allosteric
      mechanisms. Altered protein fluctuations are likely to prime the Rho GTPase
      plexin complex for interactions with additional binding partners.

PMID- 18321528
TI  - Crystal structure and RNA binding of the Tex protein from Pseudomonas aeruginosa.
AB  - Tex is a highly conserved bacterial protein that likely functions in a variety of
      transcriptional processes. Here, we describe two crystal structures of the 86-kDa
      Tex protein from Pseudomonas aeruginosa at 2.3 and 2.5 A resolution,
      respectively. These structures reveal a relatively flat and elongated protein,
      with several potential nucleic acid binding motifs clustered at one end,
      including an S1 domain near the C-terminus that displays considerable structural
      flexibility. Tex binds nucleic acids, with a preference for single-stranded RNA,
      and the Tex S1 domain is required for this binding activity. Point mutants
      further demonstrate that the primary nucleic acid binding site corresponds to a
      surface of the S1 domain. Sequence alignment and modeling indicate that the
      eukaryotic Spt6 transcription factor adopts a similar core structure. Structural
      analysis further suggests that the RNA polymerase and nucleosome interacting
      regions of Spt6 flank opposite sides of the Tex-like scaffold. Therefore, the Tex
      structure may represent a conserved scaffold that binds single-stranded RNA to
      regulate transcription in both eukaryotic and prokaryotic organisms.

PMID- 18321529
TI  - Relationship of the serotonin transporter with prolactin response to meta
      chlorophenylpiperazine in cocaine dependence.
AB  - BACKGROUND: Preclinical evidence indicates that exposure to cocaine influences
      the activity of the serotonin transporter (5-HTT) as well as several 5-HT
      receptor subtypes. However, little is known about the relationship between the 5
      HTT and 5-HT receptors following cocaine exposure in humans. OBJECTIVE: We
      examined the relationship between platelet 5-HTT, a presynaptic 5-HT measure, and
      prolactin (PRL) response to meta-chlorophenylpiperazine (m-CPP), a postsynaptic 5
      HT receptor agonist in cocaine dependent individuals. METHODS: Platelet [3H]
      paroxetine binding sites were assayed and the m-CPP challenge test was performed
      in 35 African American cocaine dependent individuals and 33 controls. Clinical
      measures included assessments of drug use severity and depression. RESULTS:
      Cocaine subjects showed reduced Bmax of [3H] paroxetine (t=4.67, p<0.01) and
      blunted PRL response to m-CPP (F=21.86, p<0.01) compared to controls. There was a
      positive correlation between Bmax and delta PRL [peak-baseline PRL] in cocaine
      subjects (r=0.50, p<0.01) but not in controls (r=0.19). ANCOVA analyses showed
      that the cocaine subgroup with moderate and severe reduction in Bmax showed a
      greater blunting in PRL response compared to the subgroup with mild Bmax
      reductions (F=9.44, p<.005). Multivariate regression models showed that the main
      effects as well as the interaction of Bmax and severity of cocaine use
      significantly contributed to impaired PRL response (F=17.90, p<.001).
      CONCLUSIONS: Disturbances in serotonin transporter binding and post-synaptic 5-HT
      receptor function seem to be associated in cocaine-dependent subjects. Severity
      of cocaine use appears to mediate this relationship. Whether there is a causal
      association between the two measures, or cocaine has separate and independent pre
      and post-synaptic effects needs to be clarified.

PMID- 18321530
TI  - The influence of turning angles on the success of non-oriented animal searches.
AB  - Animal searches cover a full range of possibilities from highly deterministic to
      apparently completely random behaviors. However, even those stochastic components
      of animal movement can be adaptive, since not all random distributions lead to
      similar success in finding targets. Here we address the general problem of
      optimizing encounter rates in non-deterministic, non-oriented searches, both in
      homogeneous and patchy target landscapes. Specifically, we investigate how two
      different features related to turning angle distributions influence encounter
      success: (i) the shape (relative kurtosis) of the angular distribution and (ii)
      the correlations between successive relative orientations (directional memory).
      Such influence is analyzed in correlated random walk models using a proper choice
      of representative turning angle distributions of the recently proposed Jones and
      Pewsey class. We consider the cases of distributions with nearly the same shape
      but considerably distinct correlation lengths, and distributions with same
      correlation but with contrasting relative kurtosis. In homogeneous landscapes, we
      find that the correlation length has a large influence in the search efficiency.
      Moreover, similar search efficiencies can be reached by means of distinctly
      shaped turning angle distributions, provided that the resulting correlation
      length is the same. In contrast, in patchy landscapes the particular shape of the
      distribution also becomes relevant for the search efficiency, specially at high
      target densities. Excessively sharp distributions generate very inefficient
      searches in landscapes where local target density fluctuations are large. These
      results are of evolutionary interest. On the one hand, it is shown that equally
      successful directional memory can arise from contrasting turning behaviors,
      therefore increasing the likelihood of robust adaptive stochastic behavior. On
      the other hand, when target landscape is patchy, adequate tumbling may help to
      explore better local scale heterogeneities, being some details of the shape of
      the distribution also potentially adaptive.

PMID- 18321532
TI  - Is convergence surprising? An examination of the frequency of convergence in
      simulated datasets.
AB  - Although convergence is recognized as a central concept in evolutionary biology,
      very few tools are available for the quantitative study of this phenomenon.
      Moreover, although many evolutionary assertions assume that convergence should be
      rare in the absence of influences on organismal phenotypes such as natural
      selection or constraint, no studies have tested whether this is the case. I
      simulate random evolution (Brownian motion model) of quantitative characters
      along phylogenies with varying numbers of terminal taxa, numbers of traits,
      variance structure, and tree balance, and quantify the amount of convergence
      observed in these datasets using four metrics. The amount of convergence observed
      in a dataset increases with increasing number of taxa and decreasing number of
      traits, approaching the maximum possible amount of convergence under certain
      circumstances. Some convergence is expected in almost all datasets. Comparison of
      empirical datasets to those produced by random evolution provides a test of
      whether empirical datasets actually show elevated levels of convergence. Out of
      three test datasets, two show more convergence than expected. Given that high
      levels of convergence can be produced simply by random evolution, no explanation
      may be necessary for instances of convergence discovered in an evolutionary
      investigation.

PMID- 18321531
TI  - The timing of TNF and IFN-gamma signaling affects macrophage activation
      strategies during Mycobacterium tuberculosis infection.
AB  - During most infections, the population of immune cells known as macrophages are
      key to taking up and killing bacteria as an integral part of the immune response.
      However, during infection with Mycobacterium tuberculosis (Mtb), host macrophages
      serve as the preferred environment for mycobacterial growth. Further, killing of
      Mtb by macrophages is impaired unless they become activated. Activation is
      induced by stimulation from bacterial antigens and inflammatory cytokines derived
      from helper T cells. The key macrophage-activating cytokines in Mtb infection are
      tumor necrosis factor-alpha (TNF) and interferon (IFN)-gamma. Due to differences
      in cellular sources and secretion pathways for TNF and IFN-gamma, the possibility
      of heterogeneous cytokine distributions exists, suggesting that the timing of
      macrophage activation from these signals may affect activation kinetics and thus
      impact the outcome of Mtb infection. Here we use a mathematical model to show
      that negative feedback from production of nitric oxide (the key mediator of
      mycobacterial killing) that typically optimizes macrophage responses to
      activating stimuli may reduce effective killing of Mtb. Statistical sensitivity
      analysis predicts that if TNF and IFN-gamma signals precede infection, the level
      of negative feedback may have a strong effect on how effectively macrophages kill
      Mtb. However, this effect is relaxed when IFN-gamma or TNF+IFN-gamma signals are
      received coincident with infection. Under these conditions, the model suggests
      that negative feedback induces fast responses and an initial overshoot of nitric
      oxide production for given doses of TNF and IFN-gamma, favoring killing of Mtb.
      Together, our results suggest that direct entry of macrophages into a granuloma
      site (and not distal to it) from lung vascular sources represents a preferred
      host strategy for mycobacterial control. We examine implications of these results
      in establishment of latent Mtb infection.

PMID- 18321533
TI  - Towards an operational system for oil-spill forecast over Spanish waters: initial
      developments and implementation test.
AB  - The ESEOO Project, launched after the Prestige crisis, has boosted operational
      oceanography capacities in Spain, creating new operational oceanographic services
      and increasing synergies between these new operational tools and already existing
      systems. In consequence, the present preparedness to face an oil-spill crisis is
      enhanced, significantly improving the operational response regarding ocean,
      meteorological and oil-spill monitoring and forecasting. A key aspect of this
      progress has been the agreement between the scientific community and the Spanish
      Search and Rescue Institution (SASEMAR), significantly favoured within the ESEOO
      framework. Important achievements of this collaboration are: (1) the design of
      protocols that at the crisis time provide operational state-of-the-art
      information, derived from both forecasting and observing systems; (2) the
      establishment, in case of oil-spill crisis, of a new specialized unit, named
      USyP, to monitor and forecast the marine oceanographic situation, providing the
      required met-ocean and oil-spill information for the crisis managers. The oil
      spill crisis scenario simulated during the international search and rescue
      Exercise "Gijon-2006", organized by SASEMAR, represented an excellent opportunity
      to test the capabilities and the effectiveness of this USyP unit, as well as the
      protocols established to analyze and transfer information. The results presented
      in this work illustrate the effectiveness of the operational approach, and
      constitute an encouraging and improved base to face oil-spill crisis.

PMID- 18321534
TI  - PCDD/Fs and PCBs in seafood species from Moreton Bay, Queensland, Australia.
AB  - Previous studies have identified elevated levels of polychlorinated dibenzo-p
      dioxins (PCDDs) in sediments and megafauna (dugongs and green turtles) in the
      marine environment of southeast Queensland, Australia. Little information exists,
      however, regarding the levels of PCDDs, polychlorinated dibenzofurans (PCDFs) and
      related polychlorinated biphenyls (PCBs) in seafood from this area. This study
      aims to establish baseline information on PCDD/F and PCB contamination in a range
      of seafood species from Moreton Bay and to investigate contaminant variability
      due to harvesting season, size, habitat location and trophic level. In addition,
      different seafood extraction methods were tested to evaluate their impact on
      lipid yields and contaminant concentration. Overall, the median TEQ(DF&PCB)
      levels in seafood from Moreton Bay were elevated compared to background levels in
      Australian marine/estuarine and retail fish. However, TEQ(DF&PCB) levels of most
      seafood analysed were below the respective EU maximum limits. High inter- and
      intraspecies variability was observed, which could be partially attributed to
      differences in trophic level, season harvested and habitat location.

PMID- 18321535
TI  - Impacts of macroalgal spores on the dynamics of adult macroalgae in a eutrophic
      estuary: high versus low hydrodynamic seasons and long-term simulations for
      global warming scenarios.
AB  - A model describing macroalgal early life stages and adult dynamics was used to
      quantify the effects of non-adult forms on the productivity of adult macroalgae
      in a eutrophic estuary. Predictions indicate that during years with mild winters
      and low rainfall, spring blooms will occur at the expense of the growth and
      reproduction of overwintering adults and without the contribution of the spore
      bank. In these circumstances, there is a positive correlation between the
      intensity of the blooms and the biomass of overwintering adults until a maximum
      threshold value. On the contrary, in years with high rainfall and low or
      inexistent biomass of overwintering adults, the onset of adult's growth depends
      on the biomass of viable dormant spores, the growing season occurs later and
      adult productivity is very limited. Long-term predictions for climate change
      scenarios suggest that, in general, global warming will have adverse affects on
      Ulva intestinalis productivity, with the adults being more affected than the
      early life stages.

PMID- 18321536
TI  - Rapid screen for truncating ATM mutations by PTT-ELISA.
AB  - Mutations in the ataxia-telangiectasia mutated (ATM) gene are responsible for the
      autosomal recessive genetic disorder, ataxia-telangiectasia (A-T). Approximately
      80% of ATM mutations found in A-T patients results in truncations, which can be
      detected by Protein Truncation Test (PTT). Conventional PTT uses SDS-PAGE
      electrophoresis to detect mobility of radiolabeled truncated protein fragments.
      In this study, we developed a non-radioactive Protein Truncation Test which
      utilizes an enzyme-linked immunosorbent assay (PTT-ELISA) to detect ATM mutations
      in eight overlapping fragments. N- and C-terminal epitopes (c-myc and V5,
      respectively) were introduced into transcription/translation products, which
      could then be detected by Sandwich ELISA. Using this assay, we screened 9 newly
      diagnosed A-T patients consecutively. Of the 18 expected mutations, 14 truncating
      mutations were independently identified by cDNA direct sequencing and/or DNA
      dHPLC analysis. PTT-ELISA detected all of these 14. Four mutations were novel.
      The PTT-ELISA provides a rapid method for detecting truncating mutations in large
      genes and should be considered prior to using more laborious or costly methods,
      such as direct sequencing.

PMID- 18321537
TI  - An fMRI investigation of memory encoding in PTSD: influence of symptom severity.
AB  - Previous studies have shown memory deficits in Post-Traumatic Stress Disorder
      (PTSD) patients, as well as abnormal patterns of brain activity, especially when
      retrieving trauma-related information. This study extended previous findings by
      investigating the neural correlates of successful memory encoding of trauma
      unrelated stimuli and their relationship with PTSD symptom severity. We used the
      subsequent memory paradigm, in the context of event-related functional magnetic
      resonance imaging, in 27 PTSD patients to identify the brain regions involved in
      the encoding of fearful and neutral faces. Symptom severity was assessed by the
      Clinically Administered PTSD Scale (CAPS) scores. It was found that memory
      performance was negatively correlated with CAPS scores. Furthermore, a negative
      correlation was observed between CAPS scores and ventral medial prefrontal cortex
      (vmPFC) activity elicited by the subsequently forgotten faces. Finally, symptom
      severity predicted the contribution of the amygdala to the successful encoding of
      fearful faces. These results confirm the roles of the vmPFC and the amygdala in
      PTSD and highlight the importance of taking into account individual differences
      when assessing the behavioural and neural correlates of the disorder.

PMID- 18321538
TI  - Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in
      the periaqueductal gray after exposure to an innate fear stimulus.
AB  - Lack of effects of clomipramine on Fos and NADPH-diaphorase double-staining in
      the periaqueductal gray after exposure to an innate fear stimulus--nitric oxide
      (NO) acts as a neurotransmitter in the rat dorsolateral periaqueductal gray
      (dlPAG), a midbrain structure that modulates fear and defensive behavior. Since
      defensive reactions can be alleviated by anxiolytic/anti-panic drugs, the present
      study tested the effect of clomipramine, a serotonin re-uptake inhibitor, on the
      activation of NO-producing neurons in the dlPAG of rats exposed to a live
      predator. Double staining was performed using Fos immunohistochemistry and NADPH
      diaphorase as techniques to mark neural activation and to detect NO-producing
      neurons, respectively. Male Wistar rats received acute or chronic (21 days)
      injections of saline or clomipramine (10 or 20 mg/kg/day) and were exposed to a
      live cat. The animals exhibited a robust defensive reaction accompanied by an
      increase in the number of Fos- and double-stained neurons in the dlPAG,
      suggesting that cat exposure activates NO-producing neurons. Such effects were
      not significantly attenuated by clomipramine treatments. The intensity of fear
      reaction correlated with the intensity of neural staining in the dlPAG,
      regardless the drug treatment. Thus, the present results reinforce the hypothesis
      that NO may coordinate defensive responses in the dlPAG and indicate that this
      mechanism may not be modulated by a serotonin re-uptake inhibitor.

PMID- 18321539
TI  - Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels
      (Camelus dromedarius) after intravenous administration.
AB  - The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.)
      dose was investigated in six camels (Camelus dormedarius). Orphenadrine was
      extracted from the plasma using a simple sensitive liquid-liquid extraction
      method and determined by gas chromatography/mass spectrometry (GC/MS). Following
      i.v. administration plasma concentrations of ORPH decline bi-exponentially with
      distribution half-life (t(1/2)(alpha)) of 0.50+/-0.07h, elimination half-life
      (t(1/2)(beta)) of 3.57+/-0.55h, area under the time concentration curve (AUC) of
      1.03+/-0.10g/hl(-1). The volume of distribution at steady state (Vd(ss)) 1.92+/
      0.22lkg(-1), volume of the central compartment of the two compartment
      pharmacokinetic model (V(c)) 0.87+/-0.09lkg(-1), and total body clearance (Cl(T))
      of 0.60+/-0.09l/hkg(-1). Three orphenadrine metabolites were identified in urine
      samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N
      dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl
      orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The
      third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH
      with molecular ion m/z 285. ORPH and its metabolites in camel were extensively
      eliminated in conjugated form. ORPH remains detectable in camel urine for three
      days after i.v. administration of a single dose of 350mg orphenadrine aspartate.

PMID- 18321540
TI  - Cysticercosis of slaughtered cattle in northwestern Ethiopia.
AB  - The occurrence of cysticercosis due to Taenia saginata in cattle slaughtered for
      meat in Amhara National Regional State, northwestern Ethiopia between September
      2005 and February 2007 was investigated. Routine meat inspection of various
      organs of 4456 cattle in eight abattoirs of this region showed that 824 (18.49%)
      were infected with Cysticercus bovis. The occurrence rate did not vary
      significantly from abattoir to abattoir (P>0.5). The tongue, masseter muscles,
      heart muscles, triceps muscles and thigh muscles were the main predilection sites
      of the cysts. Of 4102 male cattle, examined, 768 (18.72%) had cysts of C. bovis
      while 56 (15.82%) of the 354 female animals investigated were infected. The
      animals slaughtered were all adults. No significant difference in occurrence was
      recorded between the sexes. Monthly occurrence of the cysts in the animals
      revealed a rise of infected animals during the dry season.

PMID- 18321541
TI  - Anti-histone antibodies in dogs with leishmaniasis and glomerulonephritis.
AB  - The association between serum anti-histone antibodies and glomerulonephritis was
      studied in 43 dogs with leishmaniasis (Leishmania infantum). Dogs with increased
      serum creatinine levels and urine protein-creatinine ratio >1 were considered to
      have glomerulonephritis. Moderately elevated anti-histone antibodies were found
      in 38.89% (7/18) of infected dogs without glomerulonephritis, whereas 88% of dogs
      with glomerulonephritis (22/25) showed moderate or strongly elevated anti-histone
      antibodies. Prevalence of positive anti-histone antibodies reactions and mean
      serum concentration was significantly higher (P<0.001; P<0.0001) in infected dogs
      with glomerulonephritis. Correlation between anti-histone antibodies and urine
      protein-creatinine ratio was significant when groups were analysed together
      (P<0.046). Positive predictive value for glomerulonephritis of positive anti
      histone antibodies was 88%. In conclusion, high anti-histone antibodies are
      significantly associated with glomerulonephritis. Although other factors must be
      involved, dogs with moderate or strong positive anti-histone antibodies reactions
      may have a higher probability to develop glomerular lesions in canine
      leishmaniasis.

PMID- 18321542
TI  - Asymptomatic Leishmania infantum/chagasi infection in blood donors of western
      Sicily.
AB  - The purpose of this study was to evaluate whether the risk of transfusion
      transmitted visceral leishmaniasis was present in an area of western Sicily where
      the incidence of the disease is higher than the regional average. From May to
      December 2005, 1449 blood donors from Agrigento district (Sicily, Italy) were
      screened for the presence of anti-Leishmania antibodies by an indirect
      immunofluorescent antibody test (IFAT). Blood samples from IFAT-positive donors
      were examined by PCR to detect Leishmania DNA. Anti-Leishmania antibodies were
      found in 11 (0.75%) cases, among which Leishmania DNA was detected from four
      (36.4%). Particular techniques to inactivate different pathogens would be
      considered mandatory in the case of immunosuppressed recipients.

PMID- 18321543
TI  - Bacteraemia due to non-typhoidal Salmonella in Thailand: clinical and
      microbiological analysis.
AB  - The prevalence of non-typhoidal Salmonella (NTS) bacteraemia has risen in many
      countries and is probably related to the increase in HIV infection. There is
      little information regarding NTS bacteraemia in Thailand, where the HIV infection
      rate increased 13.6-fold during the period 1992-2004. This study aimed at
      surveying the prevalence as well as analysing the clinical and microbiological
      features of NTS bacteraemia at a large university hospital in Thailand. Patients
      with positive blood cultures for NTS during 2005 were retrospectively reviewed
      for their demographics, underlying diseases and microbiological profiles. A total
      of 135 patients had NTS bacteraemia. Salmonella group C was predominant. The most
      common underlying disease was HIV infection. Up to 30% of NTS isolates were
      identified as multidrug resistant. This study should prompt an alert regarding
      the evolving pattern of NTS bacteraemia in Thailand.

PMID- 18321544
TI  - Prevalence and geographical distribution of Escherichia coli O157 in India: a 10
      year survey.
AB  - Escherichia coli colonizes the human gastrointestinal tract and produces a
      variety of diseases. Escherichia coli O157 is one of the most important
      pathogenic strains reported from food-borne illnesses leading to
      enterohemorrhagic colitis. The National Salmonella and Escherichia Centre is a
      national reference centre for Salmonella and Escherichia for India; it receives
      samples from research laboratories, hospitals and institutions for serological
      identification. The present study is an epidemiological survey of E. coli O157 in
      different regions of India. The data are based on samples received from humans,
      food items, animals and the environment. A total of 17 093 isolates cultured from
      samples were received during the 10-year period of which 5678 were from human
      sources. Thirty (0.5%) human samples were positive for E. coli O157. A
      significantly high percentage of E. coli O157 were isolated from meat (0.9%,
      13/1376), milk and milk products (1.8%, 10/553), seafood (8.4%, 16/190) and water
      (1.6%, 8/486). The isolates were found to be distributed among domestic and wild
      animals, and the maximum number of isolates of E. coli O157 was detected in
      samples received from coastal belt areas. Escherichia coli O157 is widely
      distributed among humans and animals, food and environment in different
      geographical regions of India.

PMID- 18321545
TI  - Skin prick test reactivity to common allergens among women in Entebbe, Uganda.
AB  - The objectives of this study were to estimate the prevalence of atopic
      sensitization, and to identify common aeroallergens associated with atopic
      sensitization among women in Entebbe, Uganda, and to determine risk factors for
      atopic sensitization among those with and without a history of asthma or eczema.
      A case-control study was conducted within a trial of deworming in pregnancy,
      approximately 2 years after the intervention. Skin prick test reactivity was
      assessed among 20 women with a history of asthma, 25 with history of eczema and
      95 controls. Overall prevalence of reactivity was estimated by adjusting for the
      prevalence of asthma in the whole cohort. Overall skin prick test prevalence was:
      any allergen 30.7%, Blomia tropicalis 10.9%, Dermatophagoides mix 16.8%,
      cockroach 15.8%. The prevalence of a positive skin prick test was significantly
      associated with a history of asthma (70% to any allergen vs. 32%, P=0.002) but
      not with a history of eczema (44% vs. 36%, P=0.49). Women with Mansonella
      perstans had significantly reduced odds for atopic sensitization (adjusted odds
      ratio 0.14, 95% CI 0.03-0.69); women with a history of asthma were less likely to
      have hookworm (adjusted odds ratio 0.24, 95% CI 0.07-0.81) but this association
      was weaker for women with a history of eczema. [Clinical Trial No.
      ISRCTN32849447].

PMID- 18321546
TI  - Performance and reliability of the SYBR Green I based assay for the routine
      monitoring of susceptibility of Plasmodium falciparum clinical isolates.
AB  - The performance and the reliability of a SYBR Green I fluorescence-based assay to
      assess drug susceptibility in routine monitoring were evaluated in 138 Plasmodium
      falciparum clinical samples. Blood samples were studied for susceptibility to
      four antimalarial drugs by the SYBR Green I based assay, with the traditional
      [(3)H]-hypoxanthine isotopic assay as a reference. The two methods were observed
      to have similar geometric means of IC50s and IC90s, and high correlation (r=0.93
      for IC50s and r=0.94 for IC90s) for the drugs tested. The strength of agreement
      estimated by using concordance coefficient correlation was from almost perfect to
      substantial for IC50s. Our data demonstrate (i) the reliability of a simple,
      rapid and easy to use fluorescence-based assay for the routine monitoring of
      susceptibility of P. falciparum clinical isolates, and (ii) the possible switch
      from the traditional in vitro drug sensitivity assay to the SYBR Green I method,
      because previous data acquired by the isotopic assay were comparable with those
      obtained by the SYBR Green I method. We conclude that this assay will provide an
      easier method for testing drug susceptibility of malaria parasites, especially in
      malaria-endemic countries, where there is massive implementation of new
      artemisinin-based combination therapies.

PMID- 18321547
TI  - Dihydrofolate reductase I164L mutations in Plasmodium falciparum isolates:
      clinical outcome of 14 Kenyan adults infected with parasites harbouring the I164L
      mutation.
AB  - Recently, Plasmodium falciparum bearing dihydrofolate reductase (DHFR) I164L was
      isolated from Africa. Quadruple mutations containing I164L confer high-level
      resistance to antifolate antimalarials. We prospectively measured the effect of
      co-trimoxazole (CTX) prophylaxis on P. falciparum antifolate resistance
      development among HIV-infected persons. HIV-positive patients with CD4 cell count
      < 350 cells/microl (n=692) received CTX; HIV-positive patients with CD4 cell
      count > or = 350 cells/microl (n=336) and HIV-negative patients (n=132) received
      multivitamins. Malaria microscopy-positive samples (n=413) and selected
      microscopy-negative/PCR-positive samples (n=76) were analysed for DHFR mutations
      at baseline and during six months follow up. We identified I164L in 14 patients.
      Seven were malaria microscopy-positive: two failed sulfadoxine-pyrimethamine
      (SP). Among seven microscopy-negative/PCR-positive patients, none developed
      patent infections with I164L. I164L was not associated with high-level SP
      resistance or poor outcome among adults living where malaria is highly endemic.
      Surveillance to monitor spread of I164L is critical, especially among children
      and pregnant women, who are potentially a source for I164L amplification.

PMID- 18321548
TI  - Strongyloides hyperinfection syndrome: an emerging global infectious disease.
AB  - The hyperinfection syndrome (HS) caused by Strongyloides stercoralis has a high
      mortality rate (15% to 87%). A variety of risk factors and predisposing
      conditions have been described, including new immunosuppressive therapies; HTLV-1
      infection; cadaveric transplantation; immune reconstitution syndrome;
      haematological malignancies (especially lymphoma); tuberculosis; malnutrition
      secondary to chronic Strongyloides diarrhoea; international travel and
      immigration. Inhibition of Th2 cell-mediated, humoral or mucosal immunity is
      associated with HS. HS is more frequently seen in HTLV-1 than HIV patients. In
      AIDS, there is an increase in Th2 cytokines, while in HTLV-1 infection there is a
      decrease in the Th2 response, leading to an increased risk of autoinfection.
      Corticosteroid use remains the most frequent risk factor for HS. A number of
      ELISAs are useful for diagnosis and post-treatment evaluation. Once diagnosed,
      the disease may be managed effectively with anthelminthic drugs, including
      ivermectin. HS causes diverse symptoms and signs, with unusual manifestations
      leading to misdiagnosis and medical errors related to healthcare providers' lack
      of familiarity with the condition. HS is an example of an emerging tropical
      infection migrating to developed countries and requiring greater clinician
      awareness.

PMID- 18321549
TI  - Infections in travellers arriving from Australia.
AB  - An unwell traveller whose itinerary has included Australia may be infected with
      agents that are uniquely found in that country or by more cosmopolitan agents
      that exist there. This brief review will discuss some of the more common or
      important infectious disease diagnoses and discuss some features that can be
      elicited on examination or from the history that would be useful in directing
      investigation and treatment. Diseases discussed include epidemic polyarthritis,
      dengue fever, Murray Valley encephalitis, melioidosis, leptospirosis, Buruli
      ulcer, scrub typhus and spotted fever.

PMID- 18321550
TI  - The role and mechanism of progesterone receptor activation of extra-nuclear
      signaling pathways in regulating gene transcription and cell cycle progression.
AB  - Human progesterone receptor (PR) contains a polyproline motif in the amino
      terminal domain that interacts with the SH3 domain of Src and mediates rapid
      activation of c-Src and downstream MAPK (Erk-1/-2) independent of the
      transcriptional activity of PR. Forcedly target PR to different locations in the
      cell by use of mutations or tags for different cell compartments showed that
      progestin activation of Src/MAPK is mediated by PR outside the nucleus. No
      distinction could be made between the cytoplasm and cell membrane as the site of
      PR activation of Src. Therefore we can only conclude that this is an extra
      nuclear action of PR. Interestingly, the B isoform of PR which is naturally
      distributed between cytoplasm and nucleus mediated progestin activation of
      Src/MAPK, whereas PR-A that is predominantly nuclear failed to do so indicating
      that the two PR isoforms have distinct abilities to mediate rapid activation of
      signaling pathways. Due to distinct cellular locations, progestin activation of
      Src/MAPK signaling can regulate selected target genes such as cyclin D1 (CCND1)
      that lack direct PR binding response elements (PREs). Progestin induction of
      CCND1 was observed in cells expressing PR-B but not PR-BDeltaSH3 or PR-A and
      induction in the presence of PR-B was dramatically reduced in the presence of
      inhibitors of Src or MAPK. In contrast progestin induction of Sgk (serum and
      glucocorticoid regulated kinase) gene, which contains a classical PRE, was
      observed with both PR isoforms as well as PR-BDeltaSH3 and was unaffected by Src
      and MAPK inhibitors. PR bound to enhancer region of Sgk in a progestin dependent
      manner as detected by chromatin co-immunoprecipitation (ChIP) whereas no PR
      binding to CCDN1 was observed. Consistent with CCND1 data, progestin stimulation
      of cell cycle progression was only observed in cells expressing PR-B but not
      cells expressing PR-BDeltaSH3 or PR-A. These results demonstrate the importance
      of PR activation of extra-nuclear signaling pathways in regulating selected
      target genes and cell cycle progression.

PMID- 18321552
TI  - Can one learn history from the allelic spectrum?
AB  - It is well known that the neutral allelic frequency spectrum of a population is
      affected by the history of population size. A number of authors have used this
      fact to infer history given observed allele frequency data. We ask whether
      perfect information concerning the spectrum allows precise recovery of the
      history, and with an explicit example show that the answer is in the negative.
      This implies some limitations on how informative allelic spectra can be.

PMID- 18321551
TI  - Aromatase expression in the ovary: hormonal and molecular regulation.
AB  - Estrogens are synthesized by the aromatase enzyme encoded by the Cyp19a1 gene,
      which contains an unusually large regulatory region. In most mammals, aromatase
      expression is under the control of two distinct promoters a gonad- and a brain
      specific promoter. In humans, this gene contains 10 tissue-specific promoters
      that are alternatively used in various cell types and tumors. Each promoter is
      regulated by a distinct set of regulatory sequences and transcription factors
      that bind to these specific sequences. The cAMP/PKA/CREB pathway is considered to
      be the primary signaling cascade through which the gonad Cyp19 promoter is
      regulated. Very interestingly, in rat luteal cells, the proximal promoter is not
      controlled in a cAMP dependent manner. Strikingly, these cells express aromatase
      at high levels similar to those found in preovulatory follicles, suggesting that
      alternative and powerful mechanisms control aromatase expression in luteal cells
      and that the rat corpus luteum represents an important paradigm for understanding
      alternative controls of the aromatase gene. Here, the molecular and cellular
      mechanisms controlling the expression of the aromatase gene in granulosa and
      luteal cells are discussed.

PMID- 18321553
TI  - Chk2 is required for HSV-1 ICP0-mediated G2/M arrest and enhancement of virus
      growth.
AB  - ICP0 is a multi-functional herpes simplex virus type 1 (HSV-1) immediate-early
      (IE) gene product that contributes to efficient virus growth and reactivation
      from latency. Here we show that HSV-1-induced cell-cycle arrest at the G2/M
      border requires ICP0 and Chk2 kinase and that ICP0 expression by transfection or
      infection induces ATM-dependent phosphorylation of Chk2 and Cdc25C. Infection of
      cells with a replication-defective mutant virus deleted for all the regulatory IE
      genes except ICP0 (TOZ22R) induced G2/M arrest whereas a mutant virus deleted in
      addition for ICP0 (QOZ22R) failed to do so. Chk2-deficient cells and cells
      expressing a kinase-deficient Chk2 did not undergo cell-cycle arrest in response
      to TOZ22R infection. Chk2 deficiency diminished the growth of wild-type HSV-1,
      but not the growth of an ICP0-deleted recombinant virus. Together, these results
      are consistent with the interpretation that ICP0 activates a DNA damage response
      pathway to arrest cells in G2/M phase and promote virus growth.

PMID- 18321554
TI  - Modulation of enteroviral proteinase cleavage of poly(A)-binding protein (PABP)
      by conformation and PABP-associated factors.
AB  - Poliovirus (PV) causes a drastic inhibition of cellular cap-dependant protein
      synthesis due to the cleavage of translation factors eukaryotic initiation factor
      4G (eIF4G) and poly(A) binding protein (PABP). Only about half of cellular PABP
      is cleaved by viral 2A and 3C proteinases during infection. We have investigated
      PABP cleavage determinants that regulate this partial cleavage. PABP cleavage
      kinetics analyses indicate that PABP exists in multiple conformations, some of
      which are resistant to 3C(pro) or 2A(pro) cleavage and can be modulated by
      reducing potential. Cleavage reactions containing a panel of PABP-binding
      proteins revealed that eukaryotic release factor 3 (eRF3) and PABP-interacting
      protein 2 (Paip2) modulate and interfere with the cleavage susceptibility of
      PABP, whereas all other PABP-binding proteins tested do not. We show that PABP on
      cellular polysomes is cleaved only by 3C(pro) and that Paip2 does not sediment
      with polysomes. Also, viral polysomes contained only full-length PABP, however,
      cellular or viral ribosomes were equally susceptible to 3C(pro) cleavage in
      vitro. Finally, we determined that precursor 3CD and mature 3C(pro) have
      equivalent cleavage activity on purified PABP, but only 3C(pro) cleavage activity
      was stimulated by PABP-binding viral RNA. The results further elucidate complex
      mechanisms where multiple inherent PABP conformations and protein and RNA
      interactions both serve to differentially regulate PABP cleavage by 3CD, 3C(pro)
      and 2A(pro).

PMID- 18321555
TI  - Effects of NFkappaB activation on KSHV latency and lytic reactivation are complex
      and context-dependent.
AB  - Like all herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV) can
      produce either latent or lytic infection. The latent v-FLIP gene is a strong
      activator of NFkappaB, and in primary effusion lymphoma (PEL) cells, blockade of
      NFkappaB activation is associated with enhanced lytic gene expression, while
      overexpression of p65 impairs expression of reporter genes driven by lytic
      promoters. This has led to the suggestion that NFkappaB activation may promote
      latency by suppressing lytic reactivation. Here we examine in detail the effects
      of NFkappaB activation on KSHV replication in several cell types. In accord with
      earlier work, we find that inhibition of NFkappaB signaling in PEL cells is
      associated with enhanced lytic reactivation of KSHV. Similarly, in de novo KSHV
      infection of primary endothelial cells, inhibition of NFkappaB signaling leads to
      an increase in lytic gene expression and enhanced virion production. By contrast,
      KSHV-infected human foreskin fibroblasts (HFF) show no increase in spontaneous
      lytic reactivation when NFkappaB is inhibited. Moreover, if NFkappaB activation
      is always inhibitory to lytic gene expression, one might expect its activation to
      be suppressed during the lytic cycle. However, we find that NFkappaB signaling is
      strongly and consistently activated in lytically infected cells of all lineages.
      Together these data indicate that (i) the relationship of NFkappaB activation to
      latency and lytic reactivation is not uniform, but is dependent on the cellular
      context; and (ii) even though NFkappaB activation is inhibitory to lytic gene
      expression in some contexts, such inhibition is at least partially bypassed or
      overridden during lytic growth.

PMID- 18321556
TI  - Initiation of smooth-pursuit eye movements by real and illusory contours.
AB  - It is well established that elementary motion detectors are only able to code for
      the movement of a contour perpendicular to its orientation. This shortcoming
      explains why the initial direction of smooth-pursuit eye movements is directed
      orthogonal to the orientation of a moving contour independent of its veridical
      direction of motion. Here, we replicated this finding and asked whether this
      directional error can be reduced by subjects' prediction of upcoming target
      moving direction and whether this directional error also occurs during tracking
      of an illusory contour. Our results show that prediction did not abolish the
      directional error, it was only slightly reduced. On the other hand, the
      directional error was considerably diminished during pursuit initiation towards
      illusory contours and most likely reflected the amount of real stimulation
      defining the specific illusory contour. We conclude that pursuit initiation is
      driven by raw retinal image motion signals, which are not yet processed for
      figure completion.

PMID- 18321557
TI  - The role of Lecane rotifers in activated sludge bulking control.
AB  - Experiments were conducted on Lecane inermis feeding on filamentous bacteria and
      living in activated sludge to determine if the rotifers can control the growth of
      the bacteria responsible for bulking. The experiments showed that Lecane are
      capable of significantly reducing the density of Microthrix parvicella filaments.
      The rotifers not only survived the transfer from the culture to the activated
      sludge, but they multiplied quickly when foraging on filamentous bacteria. By
      reducing the number of filaments, the rotifers improved settling properties of
      the sludge. This is apparently the first report on the possibility of using
      rotifers to control bulking.

PMID- 18321558
TI  - Detection and survival of prion agents in aquatic environments.
AB  - Environmental contamination is considered a potential mechanism of transmission
      of prion diseases. Sheep scrapie and cervid chronic wasting diseases (CWD)
      epizootics are thought to be maintained by natural horizontal transmission
      through the environment. Here, we describe a method for the detection of prion
      proteins (PrPres) in aquatic environments. The procedure is based on a glycine
      buffer-mediated extraction, sonication, and an ultracentrifugation step. The
      detection limit of the method was estimated to be over 5-10 microg of infected
      tissue. In order to determine the inactivation of these agents, we spiked
      infected brain tissue in urban sewage, seawater and a buffered solution (final
      concentrations of 0.1-0.2% brain in matrix), and studied the decay of BSE- and
      scrapie-associated PrPres over time (up to 265 days). Densitometric data from
      Western blots were plotted in logarithmic scale against time. Reduction of PrPres
      titer in sewage was quantified in one logarithm after 13.5 days for BSE, 27.9
      days for mouse-passaged scrapie and 32.6 days for sheep scrapie. In the buffered
      solution, a logarithm of BSE-associated PrPres also disappeared earlier than that
      of scrapie (113.9 and 214.3 days, respectively). By means of the covariance
      analysis, these differences in the inactivation patterns were shown to be
      statistically significant. According to the data, prions may be stable for
      extended periods of time in buffered solutions like PBS, but would show limited
      survival in aquatic environmental matrices.

PMID- 18321559
TI  - Implication of hydraulic properties of bioremediated diesel-contaminated soil.
AB  - The hydraulic properties, such as hydraulic conductivity and water retention, of
      aged diesel-contaminated and bioremediated soils were examined and implications
      of the hydraulic properties for assessing bioremediation performance of soils
      were proposed. Bioremediation of diesel-contaminated soil was performed over 80 d
      using three treatments; (I) no nutrient added, column-packed soil, (II) nutrient
      added, column-packed soil, and (III) nutrient added, loosen soil. Diesel
      reduction in treatment I soil (control soil) was negligible while treatment III
      showed the greatest extent of diesel biodegradation. All treatments showed
      greatest rates of diesel biodegradation during the first 20 d, followed by a much
      retarded biodegradation rate in the remaining incubation period. Reduction of the
      degradation rate due to entrained diesel within inaccessible soil pores was
      hypothesized and tested by measuring the hydraulic properties of two column
      packed soils (treatments I and II). The hydraulic conductivity of treatment II
      soil (nutrient added) was consistently above that of treatment I soil (no
      nutrient added) at pressure heads between 0 and 15 cm. In addition, the water
      retention of treatment II soil was greater at pressure heads <100 cm (equivalent
      to pore size of >30 microm), suggesting that biodegradative removal of
      hydrocarbons results in enhanced wettability of larger soil pores. However, water
      retention was not significantly different for control and biodegraded soils at
      pressure heads >100 cm, where smaller size soil pores were responsible for the
      water retention, indicating that diesel remained in smaller soil pores (e.g., <30
      microm). Both incubation kinetics and hydraulic measurements suggest that
      hydrocarbons located in small pores with limited microbe accessibility may be
      recalcitrant to bioremediation.

PMID- 18321560
TI  - Kinetics of phenanthrene desorption from activated carbons to water.
AB  - We determined the kinetics of phenanthrene desorption from three activated
      carbons to water using Tenax beads as an infinite sink for organic compounds in
      water. Desorption kinetic data very well fitted a biphasic kinetic model based on
      the presence of two different adsorption sites, viz. low-energy sites and high
      energy sites. Rate constants for desorption to water from these two types of
      sites in the three activated carbons did not reveal a relation with activated
      carbon grain size. These rate constants were comparable to those for desorption
      of various organic compounds from hard carbon in various sediments.

PMID- 18321561
TI  - Dental tissue proportions and enamel thickness in Neandertal and modern human
      molars.
AB  - The thickness of dental enamel is often discussed in paleoanthropological
      literature, particularly with regard to differences in growth, health, and diet
      between Neandertals and modern humans. Paleoanthropologists employ enamel
      thickness in paleodietary and taxonomic studies regarding earlier hominins, but
      variation in enamel thickness within the genus Homo has not been thoroughly
      explored despite its potential to discriminate species and its relevance to
      studies of growth and development. Radiographic two-dimensional studies indicate
      that Neandertal molar enamel is thin relative to the thick enamel of modern
      humans, although such methods have limited accuracy. Here we show that, measured
      via accurate high-resolution microtomographic imaging, Neandertal molar enamel is
      absolutely and relatively thinner than modern human enamel at most molar
      positions. However, this difference relates to the ratio of coronal dentine
      volume to total crown volume, rather than the quantity of enamel per se. The
      absolute volume of Neandertal molar enamel is similar to that of modern humans,
      but Neandertal enamel is deposited over a larger volume of coronal dentine,
      resulting in lower average (and relative) enamel thickness values. Sample sizes
      do not permit rigorous intragroup comparisons, but Neandertal molar tissue
      proportions evince less variation than the modern human sample. Differences in
      three- and two-dimensional enamel thickness data describing Neandertal molars may
      be explained by dimensional reduction. Although molar tissue proportions
      distinguish Neanderthals from recent Homo sapiens, additional study is necessary
      to assess trends in tissue proportions in the genus Homo throughout the
      Pleistocene.

PMID- 18321562
TI  - Immunohistochemical study of proteins linked to apoptosis in rat fetal kidney
      cells following prepregnancy adriamycin administration in the mother.
AB  - Adriamycin is an antibiotic of the anthracycline group. In a previous study, we
      showed that administration of a single dose of adriamycin (i.p. injection, 5mg/kg
      body weight) 4 weeks before pregnancy in female Wistar rats induced histological
      changes in the fetal renal cells typical of apoptosis and also over-expression of
      heat shock proteins (HSP70). Using a similar experimental model, we have now
      examined renal cells in fetuses (gestation day 20) to investigate the pathways of
      the transduction signal of apoptosis in these cells that is induced by
      prepregnancy maternal administration of adriamycin. Immunolocalization of several
      proteins - p53, Bax, Apaf-1 and caspase 9 - which take part in the mitochondrial
      pathway of apoptosis and caspase 12, which takes part in the endoplasmic
      reticulum pathway of apoptosis, was determined. The results showed that
      adriamycin administered to the mother rat before pregnancy subsequently induced
      changes in fetal kidneys involving both the mitochondrial pathway of apoptosis,
      with increased labeling of the proteins p53, Bax, Apaf-1 and caspase 9, and the
      endoplasmic reticulum pathway of apoptosis, with increased labeling of caspase
      12. Immunolabeling of these proteins was quantified using an image analysis
      program.

PMID- 18321563
TI  - Immunolocalization of VEGF, VEGFR-1 and VEGFR-2 in lung tissues after acute
      hemorrhage in rats.
AB  - In treatment of hypovolemia it is important to reestablish normal tissue
      hemodynamics after fluid resuscitation. Vascular endothelial growth factor (VEGF)
      and VEGF receptors (VEGFR) have been identified as important in many
      physiological and pathological processes. In this study, we aimed to investigate
      the histo-physiological effects of VEGF, VEGFR-1 (flt-1) and VEGFR-2 (KDR/flk-1)
      in resuscitation with different plasma substitutes on lung tissues after acute
      hemorrhage in rats. Male Sprague-Dawley rats (n=25) were used in this study. The
      left femoral vein and artery were cannulated for the administration of volume
      expanders and for direct measurement of mean arterial blood pressure (MAP) (Power
      Lab) and heart rate (HR). Fifteen rats were bled (5 ml/10 min) and infused (5
      ml/5 min) with one of three randomly selected fluids: (a) dextran-70 (Macrodex);
      (b) gelatin (Gelofusine); or (c) physiological saline (PS, 0.9% isotonic saline)
      solutions. Five rats were bled and none were infused (hypovolemia group) and five
      rats were untreated as the control group. At the end of the experiment, rats were
      sacrificed and lung tissues were removed for routine processing and paraffin wax
      embedding. Sections of tissue were stained with hematoxylin and eosin (H&E) and
      selected blocks were then prepared for indirect immunohistochemical labeling for
      anti-VEGF, anti-VEGFR-1 and anti-VEGFR-2 primary antibodies. It was observed that
      both MAP and HR decreased parallel to blood withdrawn in this time interval. The
      MAP and HR were restored in the following periods. In the control rats, positive
      immunoreactivity of VEGF and its receptors (VEGFR-1 and VEGFR-2) were detected in
      respiratory epithelial cells, respiratory and vascular smooth muscle cells,
      alveolar cells and endothelial cells. While strong immunoreactivities of VEGF and
      VEGFR-1 were observed in the hypovolemia group, only moderate immunoreactivity of
      VEGFR-2 was seen in this group. Moderately strong immunolabeling of VEGF and
      VEGFR-1 were observed in the dextran-70, gelatin and PS resuscitated groups,
      whereas only weak immunolabeling of VEGFR-2 was observed in these groups. In
      summary, the vascular protecting effects of these factors were observed with
      fluid resuscitation, contributing to the pathophysiological changes seen in
      hypovolemia.

PMID- 18321564
TI  - Nitric oxide synthase inhibition attenuates phencyclidine-induced disruption of
      cognitive flexibility.
AB  - Schizophrenia encompasses, amongst other symptoms, a heavy load of cognitive
      dysfunctionality. Using the psychotomimetic agent, phencyclidine (PCP), we have
      previously found that PCP-induced disruptions of cognitive function in
      translational rodent models of schizophrenia are dependent on nitric oxide (NO)
      production. In the present study, male Sprague-Dawley rats were subjected to a
      Morris water maze task designed to assess cognitive flexibility (i.e. the ability
      to cope with an increasingly demanding cognitive task) by means of a "constant
      reversal learning paradigm". Experiments were conducted to evaluate the effects
      of the NO synthase inhibitor, L-NAME (10 mg/kg), on PCP-induced (2 mg/kg)
      impairments. Control animals significantly improved their learning over the first
      3 consecutive days, whereas PCP-treated animals failed to show any significant
      learning. Pretreatment with L-NAME normalized the PCP-induced disruption of
      learning to control levels. These findings suggest that PCP-induced disruptions
      of cognitive flexibility (i.e. ability to modify behaviour according to an
      increasingly demanding cognitive task) are dependent upon NO production. These
      observations, together with accumulated clinical findings, suggest that the NO
      system is a potential treatment target for cognitive dysfunctions in
      schizophrenia.

PMID- 18321565
TI  - Assessing the relationship between latent inhibition and the partial
      reinforcement extinction effect in autoshaping with rats.
AB  - Results from a variety of independently run experiments suggest that latent
      inhibition (LI) and the partial reinforcement extinction effect (PREE) share
      underlying mechanisms. Experiment 1 tested this LI=PREE hypothesis by training
      the same set of rats in situations involving both nonreinforced preexposure to
      the conditioned stimulus (LI stage) and partial reinforcement training (PREE
      stage). Control groups were also included to assess both LI and the PREE. The
      results demonstrated a significant, but negative correlation between the size of
      the LI effect and that of the PREE. Experiment 2 extended this analysis to the
      effects on LI and the PREE of the anxiolytic benzodiazepine chlordiazepoxide (5
      mg/kg, i.p.). Whereas chlordiazepoxide had no effect on LI, it delayed the onset
      of the PREE. No evidence in support of the LI=PREE hypothesis was obtained when
      these two learning phenomena were compared within the same experiment and under
      the same general conditions of training.

PMID- 18321566
TI  - Strain- and model-dependent effects of chlordiazepoxide, L-838,417 and zolpidem
      on anxiety-like behaviours in laboratory mice.
AB  - The promise of subtype-selective GABA(A) receptor drugs with anxiolytic
      properties but with a much reduced side-effect burden (compared to
      benzodiazepines) is an attainable goal. However, its achievement necessitates the
      availability of in vivo preclinical assays capable of demonstrating differences
      as well as similarities between subtype-selective agents and non-selective
      benzodiazepines. In this study, we have compared three mouse strains (NMRI,
      C57BL/6J and DBA/2) in four models of anxiety-like behaviour (plus-maze, zero
      maze, light-dark, and Vogel conflict). Furthermore, in each model, we have
      contrasted in detail the behavioural responses of each strain to the non
      selective benzodiazepine chlordiazepoxide (CDP; 5-20 mg/kg), and the subtype
      selective agents L-838,417 (GABA(A)-alpha(2/3/5); 3-30 mg/kg) and zolpidem
      (GABA(A)-alpha1; 0.3-3.0 mg/kg). The data show a complex mouse
      strainxmodelxpharmacological agent interaction. Most importantly, not all mouse
      strainxmodel test systems showed a positive response to CDP or predicted the
      response to L-838,417. This dissociation between CDP and L-838,417 opens up
      opportunities for preclinical test systems that differentiate subtype-selective
      and non-selective GABA(A) receptor agents, an attribute that might well be
      important in providing the necessary confidence for further drug development.
      Present findings suggest the need for a much greater focus on defining test
      systems appropriate for screening novel chemical entities, rather than self
      selection of models or genotypes based on responses to known pharmacological
      agents. For example, if current data with L-838,417 are confirmed with compounds
      showing similar selectivity profiles, such agents may in future be best
      identified and characterised using test systems comprising NMRI mice in the zero
      maze and/or C57 mice in the Vogel conflict and/or light-dark tests.

PMID- 18321567
TI  - Volumetric dimensional changes of dental light-cured dimethacrylate resins after
      sorption of water or ethanol.
AB  - OBJECTIVES: This study evaluated the influence of water and ethanol sorption on
      the volumetric dimensional changes of resins prepared by light curing of Bis-GMA,
      Bis-EMA, UDMA, TEGDMA or D(3)MA. METHODS: The resin specimens (15mm diameterx1mm
      height) were immersed in water or ethanol 37+/-1 degrees C for 30 days.
      Volumetric changes of specimens were obtained via accurate mass measurements
      using Archimedes principle. The specimens were reconditioned by dry storage in an
      oven at 37+/-1 degrees C until constant mass was obtained and then immersed in
      water or ethanol for 30 days. The volumetric changes of specimens were determined
      and compared to those obtained from the first sorption. RESULTS: Resins showed
      similar volume increase during the first and second sorptions of water or
      ethanol. The volume increase due to water absorption is in the following order:
      poly-TEGDMA>poly-Bis-GMA>poly-UDMA>poly-Bis-EMA>poly-D(3)MA. On the contrary, the
      order in ethanol is poly-Bis-GMA>poly-UDMA>poly-TEGDMA>poly-Bis-EMA approximately
      poly-D(3)MA. The volume increase was found to depend linearly on the amount of
      water or ethanol absorbed. SIGNIFICANCE: In the choice of monomers for
      preparation of composite resin matrix the volume increase in the resin after
      immersion in water or ethanol must be taken into account. Resins of Bis-EMA and
      D(3)MA showed the lowest values.

PMID- 18321568
TI  - Age as a modifiable risk factor for cardiovascular disease.

PMID- 18321569
TI  - The use of chondrogenic differentiation drugs to induce stem cell differentiation
      using double bead microsphere structure.
AB  - A double bead microsphere device that functions as a 3D scaffold and also
      delivers bioactive molecules to cells has been developed. The system we developed
      consists of large polymeric microspheres that were loaded with dexamethasone
      (DEXA) and coated with DHEA, which were physically immobilized using a layer-by
      layer (LbL) system. The initial step in this strategy involves the creation of
      microparticles that contain DHEA, which were simply produced using a water-in-oil
      in-water (W/O/W) emulsion method. In the second step, small sized microparticles
      containing DHEA were coated onto positively-charged poly(d,l-lactic-co-glycolic
      acid) (PLGA) microspheres that contained DEXA pretreated with
      poly(ethyleneimmine) (PEI). Microsphere constructs that contain DEXA and DHEA
      showed a significantly higher number of specific lacuna phenotypes at the end of
      a 4-week study in vitro and at the end of a 6-week study in vivo, irrespective of
      the presence of DEXA and DHEA. Therefore, the dual delivery of DEXA and DHEA can
      be used to engineer inflammation-free tissue in the vicinity of the implant.
      These double beaded PLGA microsphere constructs containing DEXA and DHEA show
      promise as coatings for implantable biomedical devices to improve
      biocompatibility and ensure in vivo performance.

PMID- 18321570
TI  - Fasting glucose improvement under dasatinib treatment in an accelerated phase
      chronic myeloid leukemia patient unresponsive to imatinib and nilotinib.

PMID- 18321571
TI  - Long-term bone marrow cultures (LTBMC) from essential thrombocythemia (ET)
      patients with or without JAK2617V>F mutation.
AB  - Approximately half of essential thrombocythemia (ET) patients and almost all with
      polycythemia vera (PV) bear the activating JAK2617V>F point mutation, which
      arises at the multipotent haemopoietic progenitor cell level. Although ET is
      mainly characterized by megacaryocyte proliferation, the cases that are positive
      for the JAK2617V>F mutation also show increased bone marrow cellularity and
      higher erythrocyte and granulocyte counts. After establishing short- and long
      term bone marrow cultures we found that the frequency of committed haemopoietic
      progenitors in the bone marrow, was not increased in JAK2617V>F positive ET
      compared to the negative ones, whereas in long-term cultures (LTBMC) JAK2617V>F
      positive ET display a growth pattern more similar to that observed in LTBMC
      produced by PV marrow cells. Our data support the notion that JAK2617V>F positive
      ET and PV represents a continuum spectrum of alterations within the same disease.

PMID- 18321572
TI  - Transient expression of an EP1-like gene encoded in Cotesia plutellae bracovirus
      suppresses the hemocyte population in the diamondback moth, Plutella xylostella.
AB  - A genome project has been launched and aims to sequence total genome of Cotesia
      plutellae bracovirus (CpBV). This on-going research has identified seven EP1-like
      (ELP) genes in the CpBV genome. A group of ELP genes has been speculated as an
      immunosuppressant encoded in Cotesia-associated bracoviruses. This study analyzed
      gene expression of these seven CpBV-ELPs in the parasitized diamondback moth,
      Plutella xylostella. Of these, six CpBV-ELPs were expressed in P. xylostella
      parasitized by C. plutellae. However, their expression levels varied in different
      tissues and parasitization stages. Especially, CpBV-ELP1 showed a persistent and
      ubiquitous expression pattern in both reverse transcriptase-polymerase chain
      reaction (RT-PCR) and immunofluorescence assays. When nonparasitized P.
      xylostella was transfected with a recombinant CpBV-ELP1 in a eukaryotic
      expression vector, CpBV-ELP1 was expressed for at least 3 days and the proteins
      were detectable in the cytoplasm of hemocytes. The transfected larvae showed
      significant reduction in total hemocyte numbers, compared with larvae injected
      with the cloning vector alone. Co-transfection with double-stranded RNA could
      knock down the expression of CpBV-ELP1 and prevented the reduction of the
      hemocyte population. This study demonstrates that CpBV-ELP1 plays a physiological
      role in suppressing host immune response presumably by its hemolytic activity
      during C. plutellae parasitization.

PMID- 18321573
TI  - Identification and characterization of an alternatively spliced variant of the
      MHC class I-related porcine neonatal Fc receptor for IgG.
AB  - The neonatal Fc receptor for immunoglobulin G (IgG) (FcRn) functions to transport
      maternal IgG to the fetal/neonatal animals and protects IgG from catabolism. The
      present study identified two pFcRn cDNAs (1.071 and 0.795kb) from intestinal
      epithelial cells. The corresponding mRNA transcripts were detected in porcine
      kidney cell line LLC-PK1, peripheral blood mononuclear cells, and porcine tissues
      by reverse transcription-PCR (RT-PCR) and Northern blot. Sequence analysis showed
      that the 1.071kb cDNA encodes the full-length pFcRn (pFcRn-L), whereas the
      0.795kb cDNA codes for a truncated pFcRn (pFcRn-S) with deletion of 92 amino
      acids matching the alpha2 domain of pFcRn-L. pFcRn-L was constitutively expressed
      by epithelial cells; however, pFcRn-S was not detectable in porcine tissues and
      cell lines although its transcript was abundant. Despite the lack of native pFcRn
      S, pFcRn-S was readily detected in transfected cells. Recombinant pFcRn-L was
      confirmed to bind IgG at pH 6.0, but not at pH 7.5; however, pFcRn-S failed to
      bind IgG at both pH 5.0-6.0 and 7.5. pFcRn-L was expressed on the cell surface
      and mainly localized in early endosomes. In contrast, pFcRn-S was absent from
      cell surface and primarily localized in the lysosome and pFcRn-S trafficking to
      lysosomes was independent of beta(2)-microglobulin (beta(2)m). The accumulation
      of pFcRn-S in the lysosome may explain the absence of native pFcRn-S protein
      expression. In addition, the trafficking of pFcRn-S to the lysosomal compartment
      suggests that in addition to sorting signals in its cytoplasmic tail, the FcRn
      structural integrity may be important for proper intracellular trafficking and
      function.

PMID- 18321574
TI  - [From the bibliometry to the financing: the SIGAPS software].

PMID- 18321575
TI  - Making fire work: pyrotechnics and natural philosophy.
AB  - Everyone is familiar with fireworks, common to festivals and celebrations across
      the world. At first glance, the history of science might appear to have little to
      do with the history of these explosive devices. However, fireworks were an
      important element of court culture in Europe, which relied on spectacle and
      festival to manifest the power of princes. From the fifteenth century, courts
      regularly set off fireworks around elaborate theatrical scenery and ephemeral
      temples, fascinating audiences with a variety of exotic motions and effects
      exploding in the night sky. Fireworks also intrigued natural philosophers, and
      over several centuries there were diverse interactions among the sciences and
      pyrotechny.

PMID- 18321576
TI  - Costimulatory strength influences the differential effects of transforming growth
      factor beta1 for the generation of CD8+ regulatory T cells.
AB  - Transforming growth factor beta1 (TGFbeta1) is a pleiotropic cytokine, capable of
      exerting diverse biologic effects. Despite its central role in multiple immune
      activities, the molecular signals responsible for shaping TGFbeta1's immunologic
      properties remain poorly elucidated. We report that costimulatory strength acts
      as a molecular switch, which influences the differential effects of TGFbeta1 on
      the effector and regulatory development of naive CD8+ lymphocytes. At low
      costimulation, TGFbeta1 inhibits proliferation of CD8+ lymphocytes and cytokine
      secretion, but at high costimulation the response to TGFbeta1 is quite different.
      High costimulation combined with TGFbeta1 generates CD8+CD25+ T lymphocytes which
      maintain robust proliferative and survival capacity in the presence of low IL-2
      concentrations. Furthermore, under these conditions, a subpopulation of CD8+ T
      lymphocytes is generated that express Foxp3, secrete IL-10, and inhibit naive T
      lymphocyte proliferation via a contact-dependent mechanism. The adoptive transfer
      of these CD8+CD25+Foxp3+ T cells into mice inoculated intravenously with B16F10
      melanoma appears to accelerate tumor progression as reflected by an increase in
      the number of pulmonary metastatic tumor foci. These findings indicate that
      costimulatory strength may act as a molecular switch in the generation of CD8+ T
      cells which possess a regulatory phenotype and the capacity to reduce antitumor
      immune responses within tumor-bearing mice.

PMID- 18321577
TI  - Perturbed thymopoiesis in vitro in the absence of suppressor of cytokine
      signalling 1 and 3.
AB  - Cytokine signals are central to the differentiation of thymocytes and their
      stepwise progression through defined developmental stages. The intensity and
      duration of cytokine signals are regulated by the suppressor of cytokine
      signalling (SOCS) proteins. A clear role for SOCS1 during the later stages of
      thymopoiesis has been established, but little is known about its role during
      early thymopoiesis, nor the function of its closest relative, SOCS3. Here, we
      find that both SOCS1 and SOCS3 are expressed during early thymopoiesis, with
      expression coincident during the double negative (DN)2 and DN3 stages. We
      examined thymocyte differentiation in vitro by co-culture of SOCS-deficient bone
      marrow cells with OP9 cells expressing the Notch ligand Delta-like1 (OP9-DL1).
      Cells lacking SOCS1 were retarded at the DN3:DN4 transition and appeared unable
      to differentiate into double positive (DP) thymocytes. Cells lacking both SOCS1
      and SOCS3 were more severely affected, and displayed an earlier block in T cell
      differentiation at DN2, the stage at which expression of SOCS1 and SOCS3
      coincides. This indicates that, in addition to their specific roles, SOCS1 and
      SOCS3 share overlapping roles during thymopoiesis. This is the first
      demonstration of functional redundancy within the SOCS family, and has uncovered
      a vital role for SOCS1 and SOCS3 during two important checkpoints in early T cell
      development.

PMID- 18321578
TI  - Molecular immunology of experimental primary tularemia in mice infected by
      respiratory or intradermal routes with type A Francisella tularensis.
AB  - The type A subspecies of Francisella tularensis is a highly virulent facultative
      intracellular bacterial pathogen, and a potential biological weapon. Recently,
      there has been renewed interest in developing new vaccines and therapeutics
      against this bacterium. Natural cases of disease, tularemia, caused by the type A
      subspecies are very rare. Therefore, the United States Food and Drug
      Administration will rely on the so-called Animal Rule for efficacy testing of
      anti-Francisella medicines. This requires the human disease to be modeled in one
      or more animal species in which the pathogenicity of the agent is reasonably well
      understood. Mice are natural hosts for F. tularensis, and might be able to
      satisfy this requirement. Tularemia pathogenesis appears to be primarily due to
      the host inflammatory response which is poorly understood at the molecular level.
      Additionally, the extent to which this response varies depending on host and
      pathogen genetic background, or by pathogen challenge route or dose is unknown.
      Therefore, the present study examined sera and infected tissues from C57BL/6 and
      BALB/c mice challenged by natural intradermal (ID) and respiratory routes with
      one of two distinct type A strains of the pathogen for cytokine and chemokine
      responses that might help to explain the morbidity associated with tularemia. The
      results show that the molecular immune response was mostly similar regardless of
      the variables examined. For instance, mRNA for the proinflammatory cytokine IL-6,
      and chemokines KC, and IP-10 was consistently upregulated at all sites of
      infection. Upregulation of mRNA for several other cytokines and chemokines
      occurred in a more tissue restricted manner. For instance, IFN-gamma was highly
      upregulated in the skin of BALB/c, but not C57BL/6 mice after ID inoculation of
      the pathogen, whilst IL-10 mRNA upregulation was only consistently seen in the
      skin and lungs.

PMID- 18321579
TI  - Exploring the Heidelberg Retinal Tomograph 3 diagnostic accuracy across disc
      sizes and glaucoma stages: a multicenter study.
AB  - PURPOSE: To investigate and compare the diagnostic accuracy of the Heidelberg
      Retinal Tomograph 3 (HRT3) diagnostic algorithms and establish whether they are
      affected by optic disc size and glaucoma severity. DESIGN: Multicenter cross
      sectional evaluation of diagnostic tests. PARTICIPANTS: Two hundred forty-two
      eyes from 139 normal subjects and 103 glaucomatous patients classified by the
      presence of a repeatable visual field (VF) defect. TESTING: Eyes were imaged by
      the HRT3. The diagnostic accuracies of Moorfields regression analysis (MRA) and
      the glaucoma probability score (GPS) was explored by sensitivity and specificity
      and area under the receiver operating characteristics curves (AUC). The analysis
      was performed globally and by optic disc size quartiles and by 3 VF severity
      groups. MAIN OUTCOME MEASURES: Sensitivity, specificity, and AUC. RESULTS: The
      GPS showed a sensitivity (80% vs. 77%) similar to and a specificity (57% vs. 67%)
      lower than that of MRA Result. It showed a higher specificity in small discs than
      MRA Result (77% vs. 68%) but a low to very low specificity in medium to very
      large discs (medium, 61%; large, 50%; very large, 26%). Moorfields regression
      analysis Global showed the highest sensitivity and specificity (68% and 78%) in
      very large discs. R. Burke linear discriminant function (RB-LDF) and cup shape
      measure (CSM) showed the best and least variable AUC across optic nerve head
      sizes and glaucoma stages. The sensitivity of both MRA and the GPS decreased at
      the earlier glaucoma stages. The MRA and GPS agreement was moderate throughout
      the entire population and in small discs and early stage, whereas it was weaker
      among the other disc size and glaucoma stage subgroups. CONCLUSIONS: HRT3
      diagnostic algorithms' accuracy is moderate. The GPS is less specific and more
      influenced by disc size than MRA. Cup shape measure and the RB-LDF offer the best
      and less variable performances across different disc sizes and glaucoma stages.

PMID- 18321580
TI  - Transient increase in intraocular pressure during a dose-tapering regime of
      systemic dexamethasone in preterm infants.
AB  - PURPOSE: To determine the intraocular pressure (IOP) profile during and after
      systemic dexamethasone treatment in preterm very low birth weight (VLBW; <1500 g)
      infants. DESIGN: A cohort study at a university-affiliated tertiary neonatal
      center. PARTICIPANTS: Twenty-seven VLBW infants who received a 3-week dose
      tapering course of systemic dexamethasone for treatment of bronchopulmonary
      dysplasia were consecutively enrolled over a period of 32 months. METHODS:
      Intraocular pressure was assessed using a handheld tonometer immediately before
      (week 0), during (weeks 1 and 3), and after (weeks 5, 7, and 9) commencement of
      the dexamethasone course. The mixed-effects models were used to evaluate the
      longitudinal IOP measurements at different time points. MAIN OUTCOME MEASURES: To
      assess the magnitude and duration of increase in IOP during systemic
      corticosteroid treatment. RESULTS: The IOP at week 1, while the infants were
      receiving the maximum dose of dexamethasone (0.6 mg/kg/day), was significantly
      higher than (1) the pretreatment IOP at week 0 (mean [+/- standard deviation]:
      19.7 [+/-3.7] vs. 16.4 [+/-3.7] mmHg, respectively) (P<0.0001), (2) the IOP when
      the infants were receiving the minimum dose of dexamethasone (0.15 mg/kg/day) at
      week 3 (19.7 [+/-3.7] vs. 15.8 [+/-4.3] mmHg) (P<0.0001), and (3) the IOP after
      the dexamethasone course had been stopped between week 5 and week 9 (19.7 [+/
      3.7] vs. 16.0 [+/-4.0], 15.3 [+/-3.5], and 14.5 [+/-3.3] mmHg for weeks 5, 7, and
      9, respectively) (P<0.0001 for all comparisons). In contrast, there was no
      significant difference between the pretreatment IOP (week 0) and IOP at week 3,
      5, 7, or 9 (P = 0.07-0.62) and in the IOP between week 3 and week 5, 7, or 9 (P =
      0.27-0.75). CONCLUSIONS: The use of a dose-tapering regime of dexamethasone is
      associated with transient increase of IOP. As IOP was significantly raised during
      the high-dose but not the low-dose treatment period, we speculate that the
      physiologic or stress dose of corticosteroids commonly advocated for treatment of
      serious neonatal conditions should be safe and unlikely to cause significant
      ocular hypertension in preterm infants.

PMID- 18321581
TI  - Rates of glaucoma medication utilization among persons with primary open-angle
      glaucoma, 1992 to 2002.
AB  - OBJECTIVE: To determine the percentage of Medicare beneficiaries with primary
      open-angle glaucoma (POAG) treated medically or surgically, utilization rates for
      each major class of glaucoma medication, and factors influencing treatment.
      DESIGN: Longitudinal observational study using data from the Medicare Current
      Beneficiary Survey (MCBS). PARTICIPANTS: Persons age 65 and older with POAG, 1992
      to 2002 (N = 6446). METHODS: By using MCBS data merged with Medicare claims,
      rates of medical and surgical treatment for participants with POAG were
      determined. Logistic analysis was used to assess factors associated with use of
      care. MAIN OUTCOME MEASURES: Receipt/nonreceipt of medical or surgical therapy in
      a year and rates of drug utilization by class and of surgery by type among
      persons who did not receive medical therapy in a year. RESULTS: On average from
      1992 to 2002, 27.4% of persons diagnosed with POAG received no medical or
      surgical treatment. Rates of nonuse increased by 3% annually (odds ratio [OR],
      1.03; 95% confidence interval [CI], 1.02-1.05). Beneficiaries with Medicaid were
      43% more likely not to receive care for POAG in a year (OR, 1.43; 95% CI, 1.20
      1.70). Hispanic, Asian, and beneficiaries of other race/ethnicity were less
      likely to receive treatment than were whites. Use of beta-blockers and miotics
      decreased, but utilization rates increased substantially for alpha-agonists,
      combination beta-blocker-carbonic anhydrase inhibitors, and especially
      prostaglandin analogs. CONCLUSIONS: Despite availability of more efficacious
      glaucoma medication classes with few side effects and findings of clinical trials
      underscoring the importance of intraocular pressure reduction in POAG patients,
      many patients with POAG continue to go untreated.

PMID- 18321582
TI  - Doctor-patient communication, health-related beliefs, and adherence in glaucoma
      results from the Glaucoma Adherence and Persistency Study.
AB  - OBJECTIVE: To use multiple data sources to determine drivers of patient adherence
      to topical ocular hypotensive therapy. DESIGN: Retrospective database and chart
      reviews in combination with prospective patient surveys. Diverse medical
      environments where insured patients in the research database seek care.
      PARTICIPANTS: Three hundred patients with a new claim diagnosis for open-angle
      glaucoma who initially were prescribed one of three prostaglandins and 103
      physicians participating in the same medical plans. METHODS: A structured
      interview addressing self-reported adherence, experiences with medication,
      communication with the physician, and health-related beliefs associated with
      adherence behavior was administered to surveyed patients. Phone interviews were
      conducted with participating ophthalmologists. MAIN OUTCOME MEASURE: Of
      adherence, medication possession ratio. RESULTS: Eight variables were associated
      independently with a lower medication possession ratio: (1) hearing all of what
      you know about glaucoma from your doctor (compared with some or nothing); (2) not
      believing that reduced vision is a risk of not taking medication as recommended;
      (3) having a problem paying for medications; (4) difficulty while traveling or
      away from home; (5) not acknowledging stinging and burning; (6) being nonwhite;
      (7) receiving samples; and (8) not receiving a phone call visit reminder. The
      multivariate model explained 21% of the variance. CONCLUSIONS: These findings
      indicate that doctor-patient communications and health-related beliefs of
      patients contribute to patient adherence. Patient learning styles that are
      associated with less concern about the future effects of glaucoma and the risks
      of not taking medications are associated with lower adherence. Specifically,
      knowledge about potential vision loss from glaucoma is a critical element that
      tends to be missed by more passive doctor-dependent patients who tend to be
      poorly adherent. These findings suggest that educational efforts in the office
      may improve patient adherence to medical therapies.

PMID- 18321583
TI  - Histologic findings in T-cell lymphoma infiltration of the optic nerve.
AB  - OBJECTIVE: To report the clinical and histologic features of lymphomatous
      infiltration of the optic nerve by systemic T-cell non-Hodgkin's lymphoma (NHL).
      DESIGN: Interventional case report. PARTICIPANT: A patient with peripheral T-cell
      NHL. METHODS: A 39-year-old man with a diagnosis of peripheral T-cell NHL, stage
      IV, with CNS involvement and decreased vision was found to have lymphomatous
      infiltration of the optic nerves. MAIN OUTCOME MEASURE: Visual acuity. RESULTS:
      Despite treatment with chemotherapy and an optic nerve sheath fenestration, the
      patient lost vision in the right eye and subsequently underwent an optic nerve
      biopsy. The histopathology showed diffuse infiltration with a clonal population
      of lymphocytic cells that were CD3 positive and CD20 negative, consistent with T
      cell NHL. CONCLUSION: Optic nerve infiltration from systemic B-cell lymphoma is
      rare and has been reported; we report an unusual case of bilateral optic nerve
      infiltration secondary to peripheral T-cell NHL.

PMID- 18321584
TI  - Medically controlled glaucoma patients show greater increase in intraocular
      pressure than surgically controlled patients with the water drinking test.
AB  - PURPOSE: To evaluate whether patients who have undergone trabeculectomy with
      mitomycin C have a different intraocular pressure (IOP) response profile after
      the water drinking test (WDT) from that of patients who are medically managed
      with a similar baseline IOP and level of visual field (VF) damage. DESIGN:
      Prospective observational study. PARTICIPANTS: Thirty glaucoma patients with IOP
      controlled by trabeculectomy and 30 with medically treated glaucoma matched for
      level of VF damage and IOP at baseline (7-14 mmHg). METHODS: All patients
      underwent the WDT, which involved drinking 1000 ml of water in 15 minutes. MAIN
      OUTCOME MEASURES: The IOP was measured before the WDT and subsequently at 15
      minute intervals for 1 hour. The peak IOP with the WDT was compared between both
      groups using Tukey post hoc multiple comparison and paired t tests. RESULTS:
      Baseline IOPs were 10.4+/-2.3 mmHg in surgically treated and 11.1+/-1.8 mmHg (P =
      0.07) in medically treated eyes. After the WDT, mean IOPs in the surgically and
      medically treated groups were 10.7+/-2.3 mmHg and 14.6+/-2.2 mmHg. Mean maximum
      IOPs were 11.7+/-2.6 mmHg and 17.3+/-2.7 mmHg in the surgically and medically
      treated groups, respectively (P<0.0001), increases of 12.5% and 56%. Ranges of
      IOP during the WDT were 2.2+/-1.3 mmHg and 5.6+/-1.9 mmHg in the surgically and
      medically treated patients (P<0.0001). CONCLUSIONS: Patients with advanced
      glaucoma who are medically controlled show greater IOP elevation and peak IOP
      after the WDT than eyes that have undergone trabeculectomy.

PMID- 18321585
TI  - Optic edge design as long-term factor for posterior capsular opacification rates.
AB  - OBJECTIVE: To compare the difference in posterior capsular opacification (PCO)
      between highly refractive silicone and hydrophobic acrylic foldable intraocular
      lenses (IOLs) with sharp and round edge designs 3 years after in-the-bag IOL
      implantation in subjects undergoing bilateral cataract surgery. DESIGN: Open
      label, prospective, randomized, multicenter clinical trial. PARTICIPANTS: Two
      hundred and eighty-eight patients with bilateral surgery for senile cataract
      operated in German university clinics, eye hospitals, and private ophthalmic
      surgical centers (Aachen, Ahaus, Bad Hersfeld, Frankfurt/Main, Jena, Rosenheim,
      and Sulzbach/Saar). INTERVENTIONS: At each center, a highly refractive index
      silicone IOL with a sharp optic edge (CeeOn) was intraindividually compared
      either with a high-refractive index silicone IOL with a round optic edge
      (PhacoFlex) in 108 patients or with an acrylic IOL with a sharp optic edge
      (AcrySof) in 139 patients. All patients received standard phacoemulsification
      with IOL implantation in the bag in both eyes from the same surgeon. A
      morphological evaluation of PCO was performed by the Evaluation of the Posterior
      Capsule Opacification (EPCO) system 1 to 2 weeks and 11 to 14 and 35 to 37 months
      after surgery. The blinded digital pictures were evaluated by an independent
      investigator. Posterior capsular opacification was statistically evaluated by
      paired comparisons of 3-year cumulative incidences of neodymium:yttrium-aluminum
      garnet (Nd:YAG) laser treatment and EPCO scores. MAIN OUTCOME MEASURES: Posterior
      capsular opacification. RESULTS: The 3-year cumulative incidences of Nd:YAG laser
      capsulotomy were 2.1% (CeeOn), compared with 2.1% (AcrySof) (risk difference, 0%;
      90% confidence interval, -3.4% to 3.4%), and 5.7% (CeeOn), compared with 17.0%
      (PhacoFlex) (risk difference, -11.4%; 90% confidence interval, -18.1% to -4.7%).
      In patients without Nd:YAG laser treatment, medians of the total area EPCO score
      were 0.0005 (CeeOn) versus 0.0440 (AcrySof) and 0 (CeeOn) versus 0.0700
      (PhacoFlex) at 3 years. Functional results, safety, and handling did not
      significantly differ for the 3 lenses. CONCLUSIONS: Our results suggest that
      modern foldable IOLs have a low incidence of PCO after 3 years. There is less PCO
      for sharp optic edge designs independent of IOL material.

PMID- 18321586
TI  - Synthesis and antioxidative activity of metalloporphyrins bearing 2,6-di-tert
      butylphenol pendants.
AB  - The novel metalloporphyrins (M=HH, Fe, Mn, Co, Cu, Zn) bearing 2,6-di-tert
      butylphenol pendants as antioxidant substituents, and a long chain hydrocarbon
      palmitoyl group have been synthesized. The oxidation of compounds by PbO2 leads
      to the formation of the corresponding 2,6-di-tert-butylphenoxyl radicals studied
      by EPR. The activity of porphyrins in lipid peroxidation has been examined using
      (1) in vitro lipid peroxidation induced by tert-butylhydroperoxide in respiring
      rat liver mitochondria, (2) in vitro lipid peroxidation in liver homogenates of
      Wistar strain rats, and (3) a model process of peroxidation of (Z)-octadec-9-enic
      (oleic) acid as a structural fragment of lipids. The activity of these compounds
      depends dramatically on the nature of metal and might be changed from
      antioxidative (M=HH, Mn, Cu, Zn) to indifferent (M=Co), and to pro-oxidative one
      (M=Fe). The anti- or pro-oxidative action of these compounds may be derived from
      the concurrence between the involvement of 2,6-di-tert-butylphenol pendants
      acting as radical scavengers and redox active metal center promoting oxidation
      processes. The results of this study suggest that the polytopic compounds
      combining in one molecule 2,6-di-tert-butylphenol pendants, metalloporphyrin
      moiety, and a palmitoyl group, are membrane active compounds and might be studied
      in an effort to find novel pharmaceutical agents.

PMID- 18321587
TI  - Experimental and theoretical study of a truly functional biomimetic molybdenum
      oxotransferase analogue system.
AB  - Density functional theory (DFT) computations at the B3LYP/Lanl2DZ level were used
      to elucidate the oxygen atom transfer (OAT) and coupled electron proton transfer
      (CEPT) reaction steps involved in the biomimetic catalytic cycle performed by
      polymer-supported Mo VIO2(NN')(2) complexes [NN'=phenyl-(pyrrolato-2-ylmethylene)
      amine] with water as oxygen source, trimethyl-phosphane as oxygen acceptor and
      one-electron oxidising agents. The DFT method employed has been validated against
      experimental data [X-ray crystal structures of a NN' ligand and a Mo VIO2(NN')2
      complex as well as kinetic data]. The rate-limiting step in the forward-OAT from
      [Mo VIO2] to PMe3 is the attack of PMe3 at an oxo ligand with DeltaG not equal
      (298 K)=64.6 kJ mol(-1). Dissociation of the product OPMe3 is facile with DeltaG(
      not equal) (298 K)=26.3 kJ mol(-1) giving a mono-oxo [Mo IVO] complex which fills
      its coordination sphere with a further PMe3 substrate with DeltaG not equal (298
      K)=39.2 kJ mol(-1). One-electron oxidation to a Mo(V) phosphane complex precedes
      the coordination of water/hydroxide. Additionally, the comproportionation of [Mo
      VIO(2)] and [Mo IVO] to dinuclear oxo-bridged [O=MoV-O-MoV=O] species has been
      calculated as the thermodynamic sink in this system and the back-OAT from dmso to
      mono-oxo [Mo IVO] to give [Mo VIO2] has been shown to involve an equilibrium
      between stereoisomeric [Mo VIO2] complexes with an activation barrier of DeltaG
      not equal (298 K)=113.1 kJ mol(-1).

PMID- 18321588
TI  - Yeast cell surface display system for determination of humoral response to active
      immunization with a monoclonal antibody against EpCAM.
AB  - Even though an immunogenic formulation of the murine monoclonal anti-EpCAM
      (epithelian cell adhesion molecule) antibody Mab 17-1A, has been shown to evoke a
      strong humoral immune response in both, monkey studies and early clinical trials,
      conventional anti-EpCAM ELISA could not identify anti-EpCAM immune response in
      relation to treatment with Mab17-1A. In contrast, usage of cellulose membranes
      prepared by SPOT technology presenting overlapping EpCAM peptides allowed the
      unequivocal determination of EpCAM related antibodies present in monkeys sera
      after immunization with IGN101. Based on such contradictory results, it was of
      high interest to compare obtained data to a different method for better
      assessment of their possible interpretation. Therefore, in the present studies,
      some EpCAM peptides, determined as reactive by binding of IgG isolated from sera
      of treated monkeys on membranes prepared by SPOT technology, were represented on
      yeast surface using the pYD1 yeast display vector system. Binding of biotinylated
      IgG from sera was detected with streptavidin-FITC and quantity of binding was
      determined by FACS measurement. Though using this completely different method,
      experiments with pre-immune and immune sera of four monkeys exemplarily are
      comparable to the results obtained by analysis with synthetic peptide arrays.

PMID- 18321589
TI  - An assessment of methods for aligning two-dimensional microscope sections to
      create image volumes.
AB  - This study assessed five different methods for aligning microscope images of
      Nissl-stained sections of mouse brain to form three-dimensional image volumes.
      Methods exploiting both image content and information from un-sectioned tissue
      were investigated. The accuracy of reconstruction was estimated using fiducials
      with known physical properties, demonstrating that methods exploiting tissue
      content produced distorted image volumes while a method using artificial
      fiducials produced the most accurate and unbiased alignment. Methodological
      issues relating to methods of volume reconstruction are discussed and it is
      recommended that methods using information from un-sectioned tissue be used
      wherever possible.

PMID- 18321590
TI  - Maze model to study spatial learning and memory in freely moving monkeys.
AB  - Many types of mazes have been used in cognitive brain research and data obtained
      from those experiments, especially those from rodents' studies, support the idea
      that the hippocampus is related to spatial learning and memory. But the results
      from non-human primates researches regarding the role of the hippocampus in
      spatial learning and memory are controversial and inconsistent with those
      obtained in rodents. This might be due to the differences of the methods used in
      non-human primates and rodents. Several kinds of maze models including two
      dimensional computerized visual maze models and three-dimensional maze models
      have been developed for non-human primates, but they all have some defects.
      Therefore, development of a maze model for non-human primates that is comparable
      with those used in rodents is necessary to solve the controversy. This paper
      describes a large-scale, three-dimensional outdoor maze model for non-human
      primates which can be used to study spatial learning and memory. Monkeys learn to
      use the maze quickly compared with two-dimensional computerized visual mazes. It
      has many advantages which could make up the limits of the existing three
      dimensional mazes in non-human primates, and can be comparable with radial arm
      mazes used in rodents. Based on the results, we believe that the new maze model
      will be valuable in many research areas, especially in studies involving spatial
      learning and memory in freely moving monkeys.

PMID- 18321591
TI  - Novel strategy to selectively label excitatory and inhibitory neurons in the
      cerebral cortex of mice.
AB  - Revealing the connections of neuronal systems is critical for understanding how
      they function. The vast majority of neurons in all cortical areas consist of
      excitatory cells whose activity is controlled by inhibitory cells. Distribution
      and projection patterns of inhibitory and excitatory cells are key information to
      understand the organization of the nervous system. To investigate axonal
      projections, we developed a method to uniquely distinguish excitatory axons from
      inhibitory ones in the cortex using transgenic mice expressing Cre recombinase in
      the Ca2+/calmodulin-dependent protein kinase IIalpha-containing neurons. These
      animals were injected by an adenoviral vector engineered so that it directs red
      fluorescent protein expression in non-Cre-expressing cells, and green fluorescent
      protein in Cre-positive neurons. We demonstrated in vitro and in vivo that GFP
      expressing neurons are GABA-immunonegative (excitatory), while the RFP-expressing
      cells are either GABAergic neurons or glial cells. One week after the viral
      vector injection RFP and GFP signals overlapped in a subset of cells but after 1
      month, the two signals showed total segregation. Six months post-inoculation, GFP
      labelling was clearly visible in axons but RFP remained only in somata and
      proximal dendrites. This technique can thus be used to differentiate excitatory
      axonal projections from inhibitory ones, and represent a unique tool in neuronal
      circuit analysis.

PMID- 18321592
TI  - Hospital characteristics associated with post-discharge suicide of severely
      depressed patients.
AB  - PURPOSE: To explore risk factors, such as characteristics of psychiatrist,
      patient and hospital at index hospitalization, associated with depressed patients
      who committed suicide within 3 months of discharge using a case-control design.
      METHODS: By linking the Taiwanese nationwide mortality database and the National
      Health Insurance dataset, all hospitalized patients with major depression who
      committed suicide within a 90-day period post-discharge during the years 2002
      2004 were selected as a study cohort (n=85). We randomly selected 425 cases (five
      for every case in the study cohort) that were matched with the study cohort in
      terms of age, gender and date of discharge as a control cohort. Cox proportional
      hazard regression was carried out to compute the adjusted 90-day survival rate
      after adjusting for other factors. RESULTS: The majority of suicide occurred 30
      days after discharge from hospitals, with a mean of 29.9 days. The adjusted
      hazard for committing suicide after hospital discharge for patients who left on
      their own initiative was 2.85 times (95% CI=1.387-5.856, p=0.004) greater than
      for those who were discharged with doctors' approval. Furthermore, the adjusted
      hazard for patients who were discharged from medical centers was higher than for
      patients discharged from regional hospitals, by a multiple of 3.38 (95% CI=1.421
      8.055, p=0.006). LIMITATIONS: Some patient-specific predictors of post-discharge
      suicide, such as suicidal ideation prior to admission, recent life events and
      social relationships with close relatives were not available. CONCLUSION: We
      conclude that, in addition to patient characteristics, hospital characteristics
      also constitute important risk factors for suicide within 90 days of discharge
      for depressed patients.

PMID- 18321593
TI  - Life events and hippocampal volume in first-episode major depression.
AB  - BACKGROUND: There are many studies on life events in depression and also several
      studies examining brain structural changes in the hippocampus of depressed
      patients. However, only few studies have focused on the association of life
      events and hippocampal volume in depression. The hypothesis of a significant
      negative association between life events and hippocampal volumes in first episode
      depression was examined. METHODS: 28 in-patients with a first episode of major
      depression were examined with high-resolution magnetic resonance imaging
      measuring hippocampal volumes. The precourse of depression was assessed with the
      Interview for the Retrospective Assessment of the Onset and Course of
      Schizophrenia and Other Psychoses (IRAOS) and life events by using the Munich
      Interview for the Assessment of Life Events and Conditions (MEL). RESULTS: A
      significant negative correlation between major life events three month before the
      onset of depression and the left hippocampal volume was found for male patients.
      In female patients no significant association between major life events and
      hippocampal volumes could be found. CONCLUSIONS: The results support the
      hypothesis that the hippocampus plays a crucial role in the pathogenesis of major
      depression in the early phase of the disorder particularly for male patients.

PMID- 18321594
TI  - Transfer of maternal colostral leukocytes promotes development of the neonatal
      immune system I. Effects on monocyte lineage cells.
AB  - Although it has been established that maternal leukocytes traffic from colostrum
      into the neonatal circulation, the effects of these cells on neonatal immunity
      are only beginning to be understood. This study examined the effects of maternal
      colostral leukocytes on development and maturation of neonatal antigen presenting
      cells. At birth, groups of neonatal calves received whole or cell-free colostrum
      (CFC) from their respective dams. Peripheral blood samples were obtained over the
      first 4 weeks of life, and expression of surface markers associated with cellular
      activation and physiological stress were monitored on monocyte lineage cells.
      Calves receiving cell-free colostrum at birth expressed elevated levels of CD11a,
      CD11c, and CD14, compared to calves receiving whole colostrum (C). Calves
      receiving cell-free colostrum had an elevated number of monocytes in the
      peripheral blood during the first 2 weeks of life, however, these cells expressed
      lower levels of expression of CD25 and MHC class I compared to calves receiving
      whole colostrum. The most significant differences in marker expression occurred
      within the first 7 days of life.

PMID- 18321595
TI  - Development and application of a quantitative real-time PCR assay to detect
      feline leukemia virus RNA.
AB  - We previously defined four categories of feline leukemia virus (FeLV) infection,
      designated as abortive, regressive, latent, and progressive. To determine if
      detectable viral DNA is transcriptionally active in the absence of antigenemia,
      we developed and validated a real-time viral RNA qPCR assay. This assay proved to
      be highly sensitive, specific, reproducible, and allowed reliable quantitation.
      We then applied this methodology, together with real-time DNA qPCR and p27 capsid
      antigen capture ELISA, to examine cats challenged with FeLV. We found that
      circulating viral RNA and DNA levels were highly correlated and the assays were
      almost in perfect agreement. This indicates that the vast majority of viral DNA
      is transcriptionally active, even in the absence of antigenemia. The real-time
      qPCR assays are more sensitive than the most commonly used FeLV diagnostic assay,
      the p27 capsid antigen capture ELISA. Application of qPCR assays may add greater
      depth in understanding of FeLV-host relationships.

PMID- 18321596
TI  - Thymic production of human FOXP3(+) regulatory T cells is stable but does not
      correlate with peripheral FOXP3 expression.
AB  - In humans functionally mature FOXP3(+) regulatory T (Treg) cells can be found
      already in the fetus, but the kinetics of their maturation is still unknown.
      Here, we show that from birth to until 10 years of age the thymic production of
      FOXP3(+) Treg cells is very stable and correlates with T-lymphopoiesis in
      general. The level of FOXP3 expression in the blood was also very stable, even
      when children and adults were compared, but there was no correlation between
      thymic and peripheral FOXP3 levels. Analysis of the cell cycle-associated marker
      Ki67 showed that a substantial fraction of peripheral FOXP3(+) cells is dividing.
      This characteristic was obtained in the periphery, since it was not observed in
      thymic CD4(+) FOXP3(+) cells. These data suggest that the thymic output of human
      Treg cells is intrinsically stable, while in the periphery the increased rate of
      proliferation severs the connection between production and homeostatic
      maintenance of the FOXP3(+) Treg cell population.

PMID- 18321597
TI  - Accumulation of allo-MHC cross-reactive memory T cells in bone marrow.
AB  - The T cells in the bone marrow (BM) have recently been shown to be enriched with
      memory T cells. We investigated in this study the reactivity of minor-antigen
      specific memory cytotoxic T lymphocytes (CTLs) induced from the BM of in vivo
      primed mice using two different antigen systems. The antigen-specific CTLs could
      be efficiently induced from the BM of immunized mice. This CTL activity was not
      observed with naive control mice, indicating that the activity was largely
      attributable to the memory T cells. Notably, these minor antigen specific CTLs
      showed cross-reactivity to allo-MHC antigens. Cold target inhibition analyses
      revealed that the same CTL populations were responsible for both anti-minor
      antigen and anti-allo-MHC reactivity. Taken collectively, these results not only
      confirmed functionally the enrichment of memory CTLs in the BM, but also
      indicated that such memory cells could cross-react with allo-MHC antigens. The
      possible role of these BM-resident memory T cells in the development of graft
      versus-host disease (GVHD) is also discussed.

PMID- 18321598
TI  - Linezolid for tympanostomy tube otorrhea caused by methicillin-resistant
      Staphylococcus aureus and multiple drug-resistant Streptococcus pneumoniae.
AB  - OBJECTIVE: To describe a consecutive series of children with refractory
      tympanostomy tube otorrhea treated with linezolid and document its clinical
      effectiveness and adverse effects. DESIGN: Retrospective, single institution case
      series. METHODS: The records of children treated with linezolid for refractory
      gram-positive otorrhea from 2003 to 2007 were analyzed for causative organisms,
      antimicrobial sensitivities, history of prior medical treatments, time to
      cessation of otorrhea, adverse effects of linezolid and recurrence of infection.
      RESULTS: Ten episodes of refractory gram-positive otorrhea treated with linezolid
      were documented among eight children during the study period. Seven were caused
      by methicillin-resistant Staphylococcus aureus and three by multiple-drug
      resistant Streptococcus pneumoniae. Prior treatment regimes included clindamycin,
      trimethoprim-sulfamethoxazole/rifampin, amoxicillin-clavulanate, and/or a third
      generation cephalosporin. Seven of eight children had failed extended courses of
      fluoroquinolone ear drops. All children were free of otorrhea by the 14th day of
      twice-daily treatment with oral linezolid at 20mg/kg/day. One child developed two
      additional episodes of S. aureus otorrhea three and 10 months after initial
      treatment. Each was successfully controlled with linezolid. There were no adverse
      effects from linezolid treatment. CONCLUSION: Oral linezolid is highly effective
      in the treatment of refractory otorrhea caused by methicillin-resistant S. aureus
      and multiple drug-resistant S. pneumoniae. It has a low risk of serious side
      effects. It is one of only a few oral agents with activity against these
      organisms and is very expensive. Linezolid should be used only when otorrhea
      cannot be treated with conventional agents or when complications of otitis media
      pose a risk to life or function.

PMID- 18321599
TI  - Intelligibility of spontaneous conversational speech produced by children with
      cochlear implants: a review.
AB  - OBJECTIVE: The emergence of cochlear implant technology has raised hopes about
      improved outcomes for children with severe and profound hearing impairments. This
      study sought to examine the current literature to help evaluate whether the new
      technology is living up to its promise specifically relative to the
      intelligibility of conversational speech produced by these children. METHOD: At
      least 20 studies to date have reported findings for the intelligibility of speech
      produced by children fitted with cochlear implants. The current review involved a
      descriptive, summary examination of 10 of these studies that analyzed spontaneous
      conversational speech. RESULTS: The review suggested that intelligibility
      outcomes for these children appear to be considerably better than we have
      historically seen in this population (i.e., prior to the development of cochlear
      implant technology). For children implanted very early it appears that progress
      toward intelligible speech is more rapid, and the development of fully
      intelligible speech may be a reasonable goal for many such children. Even for
      children implanted somewhat later, progress on speech intelligibility appears to
      continue for at least 10 years post-implantation. CONCLUSION: It would appear
      that cochlear implants are providing much better outcomes compared to older
      intervention approaches, at least relative to the intelligibility of spontaneous
      conversation.

PMID- 18321600
TI  - Hypobaric hypoxia induces dendritic plasticity in cortical and hippocampal
      pyramidal neurons in rat brain.
AB  - Hypobaric hypoxia (HH), a predisposing environmental condition at high altitude
      (HA) encountered by many mountaineers jeopardizes their normal physiology like
      motor coordination and cognitive functions. Our previous studies revealed that
      the HH induces oxidative stress and neurodegeneration, which is associated with
      spatial memory impairment in rats. However, the dendritic changes after exposure
      to different duration of HH remain largely unknown. The aim of the present study
      was to investigate the duration-dependent dendritic changes in CA1, CA3 and
      entorhinal cortex (EC) of hippocampus and layer II of prefrontal cortex (PFC)
      with spatial memory functions in rats on exposure to different duration of HH.
      The rats were exposed to simulated HA of 6100 m for 3, 7, 14 and 21 days and the
      spatial reference memory was investigated using Morris water maze (MWM) and the
      morphological alteration of CA1, CA3, EC and layer II of PFC were investigated.
      There was a significant decrease in dendritic arborization and spine number along
      with increased number of damaged neurons, after 3, 7 and 14 days of HH but after
      21 days of HH exposure the structural recovery was noted in all the regions.
      There was impairment of spatial memory after 3 and 7 days of exposure, but slight
      improvement of spatial memory was noted after 14 and 21 days of exposure. Our
      studies suggested that HH induces dendritic plasticity of PFC and hippocampal
      pyramidal neurons of rat brain, which might be associated with improvement of
      spatial memory function after 21 days of HH exposure.

PMID- 18321601
TI  - Application of PCR-SSCP for molecular epidemiological studies on the exposure of
      farm children to bacteria in environmental dust.
AB  - The environmental exposure of farm children to microorganisms in dust has become
      a focus of interest, since microbial exposure on farms has been related to a
      reduced prevalence of asthma and atopic diseases in children. Previous studies
      almost exclusively focused on the determination of microbial counts using
      conventional culturing or the determination of microbial compounds i.e.
      endotoxins. In this study PCR-SSCP (single-strand conformation polymorphism) was
      modified for characterising bacterial communities in environmental dusts and
      their sensitivity and reproducibility was validated. A fivefold repeated PCR-SSCP
      analyses of a well homogenised mattress dust, cow-shed dust, swine-shed dust,
      chicken-shed dust and a horse-shed dust sample, respectively, showed
      similarities, based on Pearson correlations, ranging from 89.7% to 95.2%. The
      reproducibility of day to day variations (five days) and gel to gel variations
      (five gels) was also around 90%. The detection limit of Escherichia coli was 7 x
      10(1) cfu g(-1) whereas Listeria monocytogenes and Bacillus licheniformis
      containing 30% spores showed visible bands at 7 x1 0(2) cfu g(-1). Application of
      this method to dust samples of 37 sheds and 63 children's mattresses showed that
      distinct farm environment dusts reflected different SSCP profiles. However,
      digital analysis of the gels showed that some bands in the profiles of shed- and
      mattress dusts were found at the same position in the gels. By excision, cloning,
      sequencing and phylogenetic analyses, these bands were identified as
      Corynebacterium tuberculostearicum, Corynebacterium mucifaciens, Staphylococcus
      epidermidis, Acinetobacter lwoffii, Brevibacterium iodinum, Brevibacterium linens
      and Arthrobacter spp, respectively. These results may reflect transfer of
      microorganisms from animal sheds to mattresses. In conclusion this study
      demonstrates that PCR-SSCP is a promising method with sensitive detection limits
      and moderate sample variances to be applied for epidemiological studies
      characterizing the exposure of farmers using environmental dust.

PMID- 18321602
TI  - The PQQ-alcohol dehydrogenase of Gluconacetobacter diazotrophicus.
AB  - The oxidation of ethanol to acetic acid is the most characteristic process in
      acetic acid bacteria. Gluconacetobacter diazotrophicus is rather unique among the
      acetic acid bacteria as it carries out nitrogen fixation and is a true endophyte,
      originally isolated from sugar cane. Aside its peculiar life style, Ga.
      diazotrophicus, possesses a constitutive membrane-bound oxidase system for
      ethanol. The Alcohol dehydrogenase complex (ADH) of Ga. diazotrophicus was
      purified to homogeneity from the membrane fraction. It-exhibited two subunits
      with molecular masses of 71.4 kDa and 43.5 kDa. A positive peroxidase reaction
      confirmed the presence of cytochrome c in both subunits. Pyrroloquinoline quinone
      (PQQ) of ADH was identified by UV-visible light and fluorescence spectroscopy.
      The enzyme was purified in its full reduced state; potassium ferricyanide induced
      its oxidation. Ethanol or acetaldehyde restored the full reduced state. The
      enzyme showed an isoelectric point (pI) of 6.1 and its optimal pH was 6.0. Both
      ethanol and acetaldehyde were oxidized at almost the same rate, thus suggesting
      that the ADH complex of Ga. diazotrophicus could be kinetically competent to
      catalyze, at least in vitro, the double oxidation of ethanol to acetic acid.

PMID- 18321603
TI  - In vitro-refolding of a single-chain Fv fragment in the presence of
      heteroaromatic thiols.
AB  - The aim of the present work was to explore the use of heteroaromatic thiol
      compounds, namely derivatives of pyridine and pyrimidine, as redox reagents for
      the in vitro-refolding of a recombinantly expressed single-chain Fv fragment
      (scFvOx). The mixed disulfide of scFvOx with glutathione was used as a starting
      material, while reduced glutathione, 4-mercaptopyridine, 2-mercaptopyrimidine, 2
      mercaptopyridine N-oxide, and the mercaptobenzene derivative thiosalicylic acid,
      respectively, served as catalysts for the formation of native disulfide bonds
      during renaturation. In contrast to thiosalicylic acid, and despite their
      significantly lower thiol pKa values, none of the heteroaromatic thiol compounds
      accelerated the apparent kinetics of in vitro-refolding compared to the naturally
      occurring peptide glutathione. However, significantly improved renaturation
      yields were observed in the presence of 4-mercaptopyridine and 2
      mercaptopyrimidine, demonstrating the usefulness of aromatic thiol compounds as
      reagents for the in vitro-refolding of antibody fragments.

PMID- 18321604
TI  - In situ gelling stimuli-sensitive block copolymer hydrogels for drug delivery.
AB  - Stimuli-sensitive block copolymer hydrogels, which are reversible polymer
      networks formed by physical interactions and exhibit a sol-gel phase-transition
      in response to external stimuli, have great potential in biomedical and
      pharmaceutical applications, especially in site-specific controlled drug-delivery
      systems. The drug may be mixed with a polymer solution in vitro and the drug
      loaded hydrogel can form in situ after the in vivo administration, such as
      injection; therefore, stimuli-sensitive block copolymer hydrogels have many
      advantages, such as simple drug formulation and administration procedures, no
      organic solvent, site-specificity, a sustained drug release behavior, less
      systemic toxicity and ability to deliver both hydrophilic and hydrophobic drugs.
      Among the stimuli in the biomedical applications, temperature and pH are the most
      popular physical and chemical stimuli, respectively. The temperature- and/or pH
      sensitive block copolymer hydrogels for biomedical applications have been
      extensively developed in the past decade. This review focuses on recent
      development of the preparation and application for drug delivery of the block
      copolymer hydrogels that respond to temperature, pH or both stimuli, including
      poly(N-substituted acrylamide)-based block copolymers, poloxamers and their
      derivatives, poly(ethylene glycol)-polyester block copolymers, polyelectrolyte
      based block copolymers and the polyelectrolyte-modified thermo-sensitive block
      copolymers. In addition, the hydrogels based on other stimuli-sensitive block
      copolymers are discussed.

PMID- 18321605
TI  - Postprandial lipaemia in patients with impaired fasting glucose, impaired glucose
      tolerance and diabetes mellitus.
AB  - AIMS: To compare the postprandial lipid responses in subjects with prediabetes
      (IFG and IGT), newly detected diabetes mellitus (NDDM) and normal glucose
      tolerance (NGT). METHODS: Postprandial lipid responses to a standard oral fat
      challenge was studied in forty-four subjects who were divided after an OGTT into
      NGT, pure impaired fasting glucose (PIFG), pure impaired glucose tolerance (PIGT)
      and NDDM. RESULTS: There was a significantly higher postprandial triglyceride
      (PPTg) response with a higher PPTg area under curve (p=0.004) and peak PPTg
      levels (p=0.003) in patients with NDDM but not with either PIFG (p>0.05) or PIGT
      (p>0.05) when compared with NGT. Overall, PPTg responses correlated significantly
      with fasting plasma glucose (p=0.001) and 2h plasma glucose (p=0.001) but not
      with age, sex, body mass index, waist, or insulin resistance. CONCLUSION:
      Subjects with newly detected diabetes mellitus displayed postprandial
      hypertriglyceridemia after a standard oral fat meal challenge while no such
      abnormality could be demonstrated in subjects with IFG or IGT. This defect is
      probably related to glycemic status and insulin resistance.

PMID- 18321607
TI  - Liver involvement in a large cohort of patients with hereditary hemorrhagic
      telangiectasia: echo-color-Doppler vs multislice computed tomography study.
AB  - BACKGROUND/AIMS: Hepatic arterio-venous malformations (HAVMs) have been found in
      74% of hereditary hemorrhagic telangiectasia (HHT) patients with multislice CT
      (MSCT). This single-blind study aimed to compare the diagnostic accuracy of echo
      color-Doppler with MSCT and identify the most sensitive ultrasound criteria
      indicating hepatic shunts. METHODS: One hundred and fifty-three HHT patients were
      systematically screened for HAVMs by biological tests, abdominal MSCT and echo
      color-Doppler. Twenty-five normal subjects and 15 cirrhotic patients were also
      included as control groups. Both intrahepatic ("color spots" and
      hypervascularization) and extrahepatic parameters (diameter, flow velocity and
      tortuosity of hepatic artery and diameter and flow velocity of portal/hepatic
      vein) were utilized. "Color-spots" are defined as subcapsular vascular spots with
      a high-velocity arterial blood flow and low resistivity index and can identify
      extremely small HAVMs. RESULTS: CT was positive in 128/153 (84%) patients and
      Doppler color spots were found in 131/153 (86%) patients. The sensitivity,
      specificity and diagnostic accuracy of "color spots" compared to MSCT were 95.3%,
      68.0% and 91.8%, respectively. The "color-spot" showed a greater correlation to
      CT (V(index)=0.655; p<0.0001) than extrahepatic criteria (V=0.317). In 20/29
      (69%) subjects, echo-color-Doppler, confirmed by CT, identified the third
      criterion for definite HHT diagnosis. CONCLUSIONS: Intrahepatic criteria was
      superior to extrahepatic criteria for identification of HAVMs. A new Doppler
      parameter ("color-spots") with an optimal accuracy for detecting HAVMs is
      proposed for easy periodic screening of HHT patients.

PMID- 18321606
TI  - Relationship of steatosis grade and zonal location to histological features of
      steatohepatitis in adult patients with non-alcoholic fatty liver disease.
AB  - BACKGROUND/AIMS: The relationship between severity and zonal location of
      steatosis and the presence of steatohepatitis and various histological features
      that define NASH has not been formally studied. METHODS: We conducted a study to
      examine the relationship of severity and zonal location of steatosis to the
      presence of NASH and to other histological features that define NASH in adult
      patients with NAFLD. Steatosis was graded as mild, moderate or severe. We
      examined the relationship between severity and zonal location of steatosis and
      the following: lobular inflammation, presence of ballooning, Mallory bodies,
      fibrosis score, and definite steatohepatitis. RESULTS: Mild, moderate and severe
      steatosis was present in 44%, 31% and 25% of biopsies, respectively. Definite
      steatohepatitis was present in 59% and advanced fibrosis in 29% of liver
      biopsies. Increasing levels of steatosis severity were positively associated with
      lobular inflammation (p<0.0001), zone 3 fibrosis (p<0.001), and definite
      steatohepatitis (p=0.02), but were unrelated to ballooning, Mallory bodies, or
      advanced fibrosis. As compared to zone 3 steatosis, pan-acinar steatosis was more
      often associated with ballooning, Mallory bodies, and advanced fibrosis.
      CONCLUSIONS: Patients with severe steatosis are more likely to have
      steatohepatitis. More studies are needed to confirm this observation and to
      explore its significance.

PMID- 18321608
TI  - Nucleic acid-sensing Toll-like receptors: beyond ligand search.
AB  - Nucleic acids from microbes were known to be immunogenic for a long time, but
      their sensors have been only recently identified. Two types of sensors, Toll-like
      receptors (TLR) and the RIG-I-like receptors (RLR), principally respond to
      nucleic acid. Discovery of these sensors have opened basic research as to how our
      immune system handles microbial nucleic acids. Recent results demonstrate that
      functional interaction between pathogen sensors is critically involved in the
      extent and type of immune responses. Moreover, responsiveness of nucleic acid
      sensing TLRs is profoundly influenced by molecules associated with TLRs or with
      nucleic acids. Our understanding of mechanisms by which TLR responses were
      controlled would contribute to development of drugs such as immunostimulatory
      nucleic acids or small chemicals antagonizing TLRs.

PMID- 18321609
TI  - Hippocampal asymmetry in exploratory behavior to vasoactive intestinal
      polypeptide.
AB  - The effects of vasoactive intestinal polypeptide (VIP) microinjected uni- or
      bilaterally into the CA1 hippocampal area of male Wistar rats at a dose of 10, 50
      and 100 ng on exploratory behavior were examined. VIP microinjected bilaterally
      at a high dose (100 ng) significantly decreased the horizontal movements, while
      at low doses (10 and 50 ng) had no effect on the exploratory activity.
      Microinjections of VIP into the left hippocampal CA1 area at doses 50 and 100 ng
      suppressed the exploratory activity, while right-side VIP administration at a
      dose 100 ng significantly increased horizontal movements compared to the
      respective controls. Vertical activity was stimulated only by VIP administered
      into the right hippocampal CA1 area at the three doses used. Neither bilateral
      nor left injections of VIP induced changes in the vertical movements. The main
      finding was the presence of hippocampal asymmetry in exploratory behavior to
      unilateral microinjections of VIP depending on the dose and the microinjected
      hemisphere.

PMID- 18321610
TI  - Synthesis, spectral characterization and bio-analysis of some organotin(IV)
      complexes.
AB  - Five novel organotin(IV) derivatives have been synthesized by refluxing
      trimethyl, triethyl, tributyl, and triphenyl and tribenzyltin chloride with
      Schiff base derived from salicylaldehyde and adenine. These compounds were
      characterized by spectroscopic (IR, (1)H, (13)C, (119)Sn-NMR, (119m)Sn Mossbauer)
      techniques and elemental analysis. Based on these results, trigonal bipyramidal
      geometry is suggested. The synthesized compounds were also treated with various
      microorganisms and found to be active.

PMID- 18321611
TI  - CoMFA analysis of dual/multiple PPAR activators.
AB  - Dual or multiple activators are agents which act at more than one biological
      target and produce synergistic therapeutic effect. Computational methods can be
      successfully employed in designing dual activators. 'Additivity of molecular
      fields' concept was recently introduced to help design new dual activators. This
      concept is employed in this work to explore the scope and limitations of the
      concept, with the help of reported PPARalpha/gamma/delta multiple activators.
      Three individual CoMFA models were first generated, followed by dual and multiple
      models. Dual PPARalpha/gamma CoMFA model could be developed successfully.
      However, dual PPARgamma/delta, dual PPARalpha/delta and multiple
      PPARalpha/gamma/delta CoMFA models could not be very well developed. This follows
      from the poor correlation observed in the PPARdelta CoMFA model.

PMID- 18321612
TI  - [Digital arteritis preceding the diagnosis of a malignant B cell lymphoma].
AB  - We report the case of a young smoker woman who developed a severe acrosyndrome of
      rapid onset, involving both hands except the thumbs. The angiography showed
      digital arteritis. Antinuclear antibodies were present at high level. Three
      months later, a large B cell lymphoma was diagnosed. Complete remission was
      achieved, but the acrosyndrome persisted with only partial improvement. The
      antinuclear antibodies disappeared. The paraneoplastic nature of the acrosyndrome
      is discussed.

PMID- 18321613
TI  - Genetic and immune correlates of the HIV infection and vaccine-induced immunity.
      Foreword.

PMID- 18321614
TI  - Immunogenicity of HSP-70, KMP-11 and PFR-2 leishmanial antigens in the
      experimental model of canine visceral leishmaniasis.
AB  - Zoonotic visceral leishmaniasis (ZVL) is a parasitic disease caused by Leishmania
      infantum/L. chagasi that is emerging as an important medical and veterinary
      problem. Dogs are the domestic reservoir for this parasite and, therefore, the
      main target for controlling the transmission to humans. In the present work, we
      have evaluated the immunogenicity of the Leishmania infantum heat shock protein
      (HSP)-70, paraflagellar rod protein (PFR)-2 and kinetoplastida membrane protein
      (KMP)-11 recombinant proteins in dogs experimentally infected with the parasite.
      We have shown that peripheral blood mononuclear cells (PBMC) from experimentally
      infected dogs proliferated in response to these recombinant antigens and against
      the soluble leishmanial antigen (SLA). We have also quantified the mRNA
      expression level of the cytokines induced in PBMC upon stimulation with the HSP
      70, PFR-2 and KMP-11 proteins. These recombinant proteins induced an up
      regulation of IFN-gamma. HSP-70 and PFR-2 also produced an increase of the TNF
      alpha transcripts abundance. No measurable induction of IL-10 was observed and
      low levels of IL-4 mRNA were produced in response to the three mentioned
      recombinant antigens. Serum levels of specific antibodies against HSP-70, PFR-2
      and KMP-11 recombinant proteins were also determined in these animals. Our study
      showed that HSP-70, KMP-11 and PFR-2 proteins are recognized by infected canines.
      Furthermore, these antigens produce a Th1-type immune response, suggesting that
      they may be involved in protection. The identification as vaccine candidates of
      Leishmania antigens that elicit appropriate immune responses in the canine model
      is a key step in the rational approach to generate a vaccine for canine visceral
      leishmaniasis.

PMID- 18321615
TI  - Dramatic improvement in FMD DNA vaccine efficacy and cross-serotype antibody
      induction in pigs following a protein boost.
AB  - To overcome the low and slow development of humoral antibody often observed with
      DNA vaccines we applied a prime-boost strategy. When FMD DNA vaccine P1-2A3C3D
      and pGM-CSF primed pigs were boosted with inactivated foot-and-mouth disease
      virus (FMDV) antigen and recombinant 3D (without adjuvant) an average 36-fold
      increase in the FMDV antibody response was observed compared to conventional
      vaccination, that included a log(10) virus neutralising titre increase. Most
      remarkably, a significant level of cross-serotype reactivity was observed against
      A, C and Asia1 in the virus neutralisation and ELISA tests. This prime-boost
      strategy fully protected pigs from a heterologous challenge.

PMID- 18321616
TI  - A CpG oligodeoxynucleotide acts as a potent adjuvant for inactivated rabies virus
      vaccine.
AB  - To develop a CpG containing oligodeoxynucleotide (CpG ODN)-enhanced rabies
      vaccine for stimulating an earlier production of rabies virus neutralizing
      antibody (RVNAb) with high titers, we designed a CpG ODN (BW006) and evaluated
      its adjuvant activities in enhancing the immune response to rabies vaccine with
      or without aluminum in mice. It was found that BW006 could facilitate the rabies
      vaccine to induce an earlier and more vigorous RVNAb response, resulting in more
      effective protection of mice from rabies virus challenge. In addition, three
      shots of rabies vaccine with BW006 induced compatible RVNAb level with that
      induced by five shots of aluminum-adjuvanted rabies vaccine. These data reveal
      that BW006 could be used as a promising adjuvant to replace of or combine with
      aluminum for developing more effective rabies vaccines.

PMID- 18321617
TI  - Immunogenetic basis of HIV-1 infection, transmission and disease progression.
AB  - Susceptibility to HIV-1 infection and rate of disease progression to AIDS are
      complex traits modulated by environmental and genetic factors. Studies on large
      AIDS cohorts and their meta-analyses have identified numerous AIDS restriction
      genes that regulate HIV cell entry (particularly chemokine co-receptors and their
      ligands), acquired and innate immunity (major histocompatibility complex (MHC),
      killer immunoglobulin-like receptors (KIRs), and cytokines) and others that
      influence outcome of HIV infection. However, vast inter-individual variability is
      often observed and some rare individuals like 'long-term non-progressors (LTNPs)
      or exposed uninfected' (EUs) appear to be protected due to natural resistance. A
      better understanding of genetic basis of such a 'natural resistance' to infection
      would bear important implications in designing therapeutic vaccine designs. The
      genetic variants that could limit AIDS vary in different populations. We have
      studied genetic variations in the MHC, cytokines and CCR2-CCR5 loci in the Asian
      Indian HIV-infected population and compared with other global populations.

PMID- 18321618
TI  - Acute perioperative normovolaemic haemodilution in major maxillofacial surgery.
AB  - Extensive blood loss can occur when patients have major operations for head and
      neck neoplasia. The risks and costs of allogeneic blood transfusion have been
      well documented. Acute perioperative normovolaemic haemodilution (APNH) is a
      method of saving blood and autologous transfusion. The purpose of this study was
      to compare a group of patients having major head and neck operations who had
      APNH, with a historical group, to assess the need for allogeneic transfusion. Of
      the 21 patients who had APNH only one patient required allogeneic blood. In the
      historical group of 24 patients, 15 patients had required allogeneic blood
      (p=0.0001). APNH is an economic, safe and practical way of saving blood.

PMID- 18321619
TI  - Researching labour and birth events using health information records:
      methodological challenges.
AB  - OBJECTIVES: as little has been published about the particular challenges of
      researching labour and birth events using health information records (HIRs), this
      study aimed to describe the methodological and quality assurance (QA) issues
      encountered in reviewing such records for a study of health and recovery after
      operative birth, and to report on how these issues were tackled. DESIGN AND
      SETTING: retrospective review of HIRs, recording details of the labour and birth
      events of 394 women for 630 confinements at 32 hospitals, chiefly situated in the
      State of Victoria, Australia. PARTICIPANTS: three hundred and ninety-four women,
      a subset of a cohort of 534 women participating in the Health and Recovery after
      Operative Birth Project, who gave consent to review of their HIRs. METHODS: a
      data abstraction form (DAF) and comprehensive accompanying study manual were
      designed, with the form's layout based on the HIR used by the hospital where the
      majority of confinements occurred. Amendments were made following piloting of the
      DAF. Three data abstractors were carefully trained for the task of reviewing
      records, and issues were dealt with as they arose at fortnightly meetings. Double
      data abstraction (cross-coding) exercises were conducted three times during the
      project and reported on for QA purposes. FINDINGS: a number of limitations were
      found with labour and birth event data recorded in the HIRs. For example,
      maternal position in active second stage labour could not be established for 65%
      of births, documentation of onset of second stage was not accompanied by
      definitive evidence for second stage onset in 23.9% of cases, and maternal
      position at birth was missing in 26.4% of cases. Other relevant variables also
      proved problematic. For example, infant head circumference was not documented for
      24.4% of births, and 52.9% of records did not document maternal height. Time and
      effort put into data abstractor training, and careful design and piloting of the
      DAF enabled both the form and data abstraction methods to be adapted following
      recognition of some of the limitations identified with the records, and also
      allowed subsequent analytic possibilities to be maximised. Cross-coding exercises
      also increased data abstractor reliability. KEY CONCLUSIONS AND IMPLICATIONS FOR
      PRACTICE: the likelihood of obtaining reliable data from HIRs is increased by a
      keen awareness of the challenges presented by the records themselves, careful
      training of staff, careful DAF design which allows for documentation of problems,
      conducting QA checks such as cross-coding exercises, and cautious reporting of
      findings with appropriate recognition of inherent limitations of the method.

PMID- 18321620
TI  - Fathers' functional status during pregnancy and the early postnatal period.
AB  - OBJECTIVE: to determine the functional status of fathers whose wives were
      pregnant or in the early postnatal period. SAMPLE AND SETTING: the research
      population comprised 3750 fathers whose wives were pregnant or in the early
      postnatal period, and who were registered at a primary health clinic in the
      province centre. The research sample comprised 275 husbands of women who were
      registered at these clinics and who were in at least their 28th week of a normal
      (not at-risk) pregnancy with a single fetus, or who were in the early postnatal
      period (6-8 weeks postnatal) following birth of a single baby between the 38th
      and 42nd week without complications. Due to fathers declining to participate in
      the study or unable to participate because of busy work schedules, the research
      was completed with 155 fathers-to-be and 93 fathers; in total, 90% of the target
      sample was reached. A sociodemographic survey and the Inventory of Functional
      Status-Fathers were used for data collection and to describe the functional
      abilities of fathers-to-be and fathers. FINDINGS: no statistically significant
      differences were found in functional status between the husbands of pregnant
      women and the husbands of women in the early postnatal period. Number of
      pregnancies was not significantly related to any of the seven subscales of
      fathers' functional status; age of husband, length of marriage and occupation of
      wife were significantly related to one subscale; occupation of husband and health
      insurance were significantly related to two subscales; income status of husband
      and educational level of wife were significantly related to three subscales; and
      educational level of husband was significantly related to four subscales.
      CONCLUSION: although there was no significant difference in functional status for
      the husbands of pregnant women and the husbands of postnatal women,
      sociodemographic factors were found to have an effect.

PMID- 18321621
TI  - Analysis of biomechanical effect of stem-end design in revision TKA using Digital
      Korean model.
AB  - BACKGROUND: The stem-end pain after revision total knee arthroplasty has been
      clinically reported around the diaphyseal region of the tibia, and the stem-end
      design has been recognized as one of the causes of the stem-end pain. But there
      are few reports about the biomechanical characteristics of different stem-end
      designs on revision total knee arthroplasty. The objective of this study is to
      investigate the biomechanical effect of the stem-end design in revision total
      knee arthroplasty. METHODS: Three-dimensional finite element models of a tibia
      and implants for revision total knee arthroplasty with various stem-end design
      parameters were developed. The tibia model was chosen from 50 male cadavers to
      represent the standard Korean male. The contact pressures and von Mises stresses
      around the stem-end were calculated under axial loading. FINDINGS: The longer
      stem length, the bigger stem diameter, the stronger press-fit, and no slot shape
      increased both peak contact pressures and von Mises stresses. The location of
      peak contact pressures coincided with the location of stem-end pain reported in
      clinical studies. INTERPRETATION: Different stem-end designs altered the contact
      pressures or stress concentrations to the tip of the stem. The location of peak
      contact pressures or von Mises stresses suggested there may be a biomechanical
      factor to transfer load or generate stress concentration at the location of the
      stem-end pain in the diaphysis.

PMID- 18321622
TI  - Analysis of in vivo mutation data can inform cancer risk assessment.
AB  - Under the new U.S. Environmental Protection Agency (EPA) Cancer Risk Assessment
      Guidelines [U.S. EPA, 2005. Guidelines for Carcinogen Risk Assessment. EPA/630/P
      03/001B, March 2005], the quantitative model chosen for cancer risk assessment is
      based on the mode-of-action (MOA) of the chemical under consideration. In
      particular, the risk assessment model depends on whether or not the chemical
      causes tumors through a direct DNA-reactive mechanism. It is assumed that direct
      DNA-reactive carcinogens initiate carcinogenesis by inducing mutations and have
      low-dose linear dose-response curves, whereas carcinogens that operate through a
      nonmutagenic MOA may have nonlinear dose-responses. We are currently evaluating
      whether the analysis of in vivo gene mutation data can inform the risk assessment
      process by better defining the MOA for cancer and thus influencing the choice of
      the low-dose extrapolation model. This assessment includes both a temporal
      analysis of mutation induction and a dose-response concordance analysis of
      mutation with tumor incidence. Our analysis of published data on riddelliine in
      rats and dichloroacetic acid in mice indicates that our approach has merit. We
      propose an experimental design and graphical analysis that allow for assessing
      time-to-mutation and dose-response concordance, thereby optimizing the potential
      for in vivo mutation data to inform the choice of the quantitative model used in
      cancer risk assessment.

PMID- 18321623
TI  - Improving the quality of risk assessments in Canada using a principle-based
      approach.
AB  - In 2000, the Government of Canada issued the "Framework for Science and
      Technology Advice" (FSTA). This official government policy directive mandates
      that decision-making to protect human health and the environment should be
      carried out in a timely, predictable, and efficient manner. It also leaves no
      doubt that quality assurance and quality control (QA/QC) are required for both
      technical data and the decision-making process itself. Since current publicly
      available Canadian risk assessment guidance does not directly address quality
      management for the decision-making process, an evaluative scheme for CEPA risk
      assessments was created. For each of the six FSTA principles (early issue
      identification, inclusiveness, sound science and science advice, uncertainty and
      risk, openness and transparency, review) specific expectations were developed for
      performance measurement purposes. This scheme addresses the FSTA requirement for
      a policy compliance checklist. It could serve as the basis for quality assurance
      audits during risk assessment production and quality control audits in subsequent
      review of the risk assessment process. Among other things, it could also improve
      the integration of science advice, policy objectives and general risk
      communication by enhancing decision-making openness and transparency.

PMID- 18321624
TI  - From life insurance to safer sex--reflections of a marketing man.
AB  - Much of the writing on health in developing countries focuses on the public
      sector rather than the private market, and on providers rather than on consumers.
      A more consumer-oriented perspective would regard the transactions by which most
      people in most poor countries buy healthcare as the norm, just one among many
      purchases of a personal service which all of us, as consumers, have to make. This
      paper contends that asymmetric information is not confined to health and
      medicine, but is a common problem for consumers whatever the GDP of the country
      they live in, and however rich and poor they may be. Understanding how consumers
      overcome these problems yields insights into the ways in which providers have to
      market their services, and into what, if anything, governments and donors can do
      to extend, improve or regulate the private healthcare market.

PMID- 18321625
TI  - Communicating a terminal prognosis in a palliative care setting: deficiencies in
      current communication training protocols.
AB  - The goal of this study was to understand the use and effectiveness of current
      communication protocols in terminal prognosis disclosures. Data were gathered
      from an interdisciplinary palliative care consultation service team at a Veterans
      Hospital in Texas, USA. Medical communication guidelines, a consistent component
      in United States palliative care education, propose models for delivery of bad
      news. However, there is little empirical evidence that demonstrates the
      effectiveness of these guidelines in disclosures of a terminal prognosis. Based
      on ethnographic observations of terminal prognosis meetings with dying patients,
      palliative care team meetings, and semi-structured interviews with palliative
      care team practitioners, this study notes the contradictory conceptualizations of
      current bad news communication guidelines and highlights that communicating a
      terminal prognosis also includes (1) adaptive communication based on the
      patient's acceptability, (2) team based/family communication as opposed to
      physician-patient dyadic communication, and (3) diffusion of topic through
      repetition and definition as opposed to singularity of topic. We conclude that
      environmentally based revision to communication protocol and practice in medical
      school training is imperative.

PMID- 18321627
TI  - The creation of the concept of an antidepressant: an historical analysis.
AB  - The concept of an "antidepressant" implies a drug that acts in a disease specific
      way to reverse the neuropathological basis of the symptoms of depression.
      However, there is little scientific research that could confirm this view. This
      paper reports an historical study of the emergence of the concept of the
      antidepressant and the social forces that influenced its adoption. Historical
      literature documents the increasing importance of the specificity of medical
      treatments in the 20th century and the increased power that they conferred on
      medical practitioners. In the case of depression, stimulants were used as
      treatment from the 1940s. During the 1950s the anti-tuberculous drugs iproniazid
      and isoniazid started to be portrayed as more specific than stimulants, even
      though their stimulant effects were well documented. When imipramine was
      suggested to be effective in depression, it was presented solely as acting in a
      disease specific way and it was soon referred to as an "antidepressant". The idea
      that some drugs have a specific action on the underlying basis of depression
      caught on rapidly and was well established by the 1960s before any evidence was
      available to support this view. Forces that could have driven the adoption of
      this view include the psychiatric profession's desire to integrate with general
      medicine to improve its social status and to move away from the asylum into the
      community. Physical interventions and drug treatments helped to boost its medical
      credentials and antidepressant drugs provided a convenient form of medical
      treatment for community-based distress. They also helped the profession to
      counter attacks from the antipsychiatry movement. The pharmaceutical industry too
      helped to establish and disseminate the view of antidepressants as disease
      specific treatments in order to distinguish them from non-specific drugs. This
      study raises questions about the view that psychiatry was transformed into a
      modern medical enterprise in the 1950s and 1960s by the introduction of disease
      specific drugs.

PMID- 18321628
TI  - Future health systems: Why future? Why now?

PMID- 18321629
TI  - Doing well by doing good. The relationship between formal volunteering and self
      reported health and happiness.
AB  - In this paper, we examine whether engaging in voluntary work leads to greater
      well-being, as measured by self-reported health and happiness. Drawing on data
      from the USA, our estimates suggest that people who volunteer report better
      health and greater happiness than people who do not, a relationship that is not
      driven by socio-economic differences between volunteers and non-volunteers. We
      concentrate on voluntary labor for religious groups and organizations and using
      second stage least square regressions we find that religious volunteering has a
      positive, causal influence on self-reported happiness but not on self-reported
      health. We explore reasons that could account for the observed causal effect of
      volunteering on happiness. Findings indicate that low relative socio-economic
      status is associated with poor health both among those who volunteer and those
      who do not. Low status, however, is associated with unhappy states only among
      those who do not volunteer, while volunteers are equally likely to be happy
      whether they have high or low status. We propose that volunteering might
      contribute to happiness levels by increasing empathic emotions, shifting
      aspirations and by moving the salient reference group in subjective evaluations
      of relative positions from the relatively better-off to the relatively worse-off.

PMID- 18321630
TI  - Associations of polybrominated diphenyl ethers (PBDEs) in breast milk and dietary
      habits and demographic factors in Taiwan.
AB  - The aim of this study was to examine levels of PBDEs in breast milk associated
      with seafood consumptions of Taiwanese mothers. Our participants were selected
      from healthy women recruited between December 2000 and November 2001 from a
      medical center in central Taiwan. The congeners of PBDEs in 20 milk samples were
      analyzed by a gas chromatograph with a high resolution mass detector. The mean
      level of BDE47 in breast milk from mothers with pre-pregnant BMI <22.0kg/m2 had a
      significantly higher magnitude compared to those with pre-pregnant BMI > or =
      22.0kg/m2 (1.59 vs. 0.995ng/g lipid, p=0.041). We did not find significant
      correlations between PBDEs exposure levels and women's age, parity, blood
      pressure, annual household income, and education level. Women who ate more fish
      and meat did not show significantly higher PBDE levels than those who ate less,
      but a significant difference in PBDE levels was demonstrated between the higher
      (2.15ng/g lipid) and lower (3.98ng/g lipid) shellfish consuming subjects
      (p=0.002) after an adjustment for the confounders. The ratios of PCB153/BDE47,
      PCB153/BDE153, and PCB153/PBDEs were significantly correlated with frequent
      consumption of fish and shellfish. The PCB153/BDE153 ratio was not associated
      with the other dietary habits (i.e. meat). The ratios of PCB153/PBDEs may
      therefore be a new indicator for exposure as a result of seafood consumption.

PMID- 18321631
TI  - The effects of over-expression and suppression of Cdc25A on the S-phase
      checkpoint induced by benzo(a)pyrene.
AB  - Our previous results have indicated that Cdc25A is involved in benzo(a)pyrene
      (BaP)-induced S-phase checkpoint in 16HBE cells and A549 cells. In this paper, we
      reported the changes of the downstream molecular pathway of Cdc25A and the
      effects of over-expression and suppression of Cdc25A on BaP-induced S-phase
      checkpoint. In the S-phase checkpoint induced by BaP the reduction of Cdc25A
      contributes to cyclin A inhibition. Over-expression of Cdc25A abrogated BaP
      induced S-phase arrest in 16HBE cells and concomitantly the expression levels of
      Cdk2 and cyclin A were not obviously changed by BaP when compared with the
      control. Cdc25A down-regulation by RNA interference (RNAi) prolonged the S-phase
      arrest induced by BaP and decreased clearly the expression levels of cyclin A and
      cyclin E. Therefore, our results further demonstrated that Cdc25A was an effector
      in Chk1-Cdc25A-cyclin A/Cdk2 pathway of S-phase checkpoint elicited by the
      carcinogen BaP in 16HBE cells.

PMID- 18321632
TI  - Changes in color and color coordinates of an indirect resin composite during
      curing cycle.
AB  - OBJECTIVES: To measure the color changes of indirect resin composites during
      curing cycle and to determine the influence of shade group on these changes.
      METHODS: One brand (belleGlass NG), divided into three shade groups (EN, OD and
      TL), was investigated. Resin composite was packed into a mold (BC) and was cured
      with a light-curing unit (C1). Secondary curing was performed in the proprietary
      curing chamber (C2). Color was measured at BC, C1 and C2 conditions. Changes in
      color and color coordinates were calculated and repeated measures three-way ANOVA
      was performed. Each pair of compared-condition in the curing cycle was set as a
      repeated variable. RESULTS: Net curing color change (C2-BC) was in the range of
      1.0-10.1DeltaEab* units. Based on ANOVA for the color changes, DeltaEab* was
      influenced by the compared-condition, the shade group and the shade designation
      (p<0.01). Changes in color coordinates varied by the shade group. CONCLUSION:
      Changes in color during curing cycle were perceptible in several shades by the
      condition (DeltaEab*>3.7); therefore, clinical practice of shade matching should
      consider these color changes.

PMID- 18321633
TI  - Vaginal reconstructive surgery for severe pelvic organ prolapses: a 'uterine
      sparing' technique using polypropylene prostheses.
AB  - OBJECTIVE: The Ulmsten's "Integral Theory" for pelvic floor dysfunctions is based
      on the need to reinforce fascias and ligaments with prostheses to obtain a
      reconstitution of the pelvic floor's anatomy. In September 2004 we developed a
      "uterine-sparing" surgical technique to correct such pathologies and in this
      paper we present results obtained. Primary outcome was to evaluate the
      technique's efficacy, secondary outcomes the resolution of stress urinary
      incontinence, postoperative pain (VAS scale), safety and complications. STUDY
      DESIGN: This prospective study included patients affected by stage 3 and 4
      uterine-vaginal prolapse who wished to conserve their uterus. Those with (1)
      minor degrees of severity, (2) unfit for surgery, (3) with a clear indication to
      hysterectomy (i.e. endometrial cancer), (4) with an elevated operative risk
      (American Society of Anaesthesiologists-ASA score III and IV), (5) previous
      vaginal surgeries and (6) with moderate/severe defecation problems were excluded.
      The technique consisted in a sacrospinous colposuspension with polypropylene
      mesh. The pelvic status was classified according to the international Pelvic
      Organ Prolapse staging system (POP-Q). Postoperative pain was scored with the VAS
      Scale. All patients were given the King's Health questionnaire, the Pelvic Organ
      Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12) and the Wexner
      questionnaire. RESULTS: From September 2004 to November 2006 we treated 80
      patients. Polypropylene prostheses (Gynemesh-Soft PS, 10cmx15cm - GyneMesh,
      Gynecare Ethicon - Somerville, NJ, USA) were used to reconstruct the pubo-cervix
      or the recto-vaginal fascia. We performed an anterior-central vaginal
      reconstruction in 35 (43.8%) patients, central-posterior in 25 (31%) and total
      reconstruction in 20 (25%). The median follow-up was 21 months (range 18-26). The
      severe pelvic prolapse, evaluated with the POP-Q System, was completely treated
      in all the patients and no recurrences were observed. The urodynamic examination
      showed a complete resolution of the stress urinary incontinence in 10 patients
      (83%). Sexual activities improved in all patients. We recorded three vaginal
      erosions and one patient complained of a postoperative dyspareunia. CONCLUSIONS:
      This pilot study suggests that our technique is safe and effective and can
      efficiently repair the pelvic organs prolapse, without undergoing hysterectomy
      and with a low rate of vaginal erosions.

PMID- 18321634
TI  - Ion homeostasis and the functional roles of SERCA reactions in stimulus-secretion
      coupling of the pancreatic beta-cell: A mathematical simulation.
AB  - The present paper concerns with ion homeostatic reactions in view of stimulus
      secretion coupling of the beta-cell, including Ca2+ fluxes of the endoplasmatic
      reticulum (ER). A steady state of cytosolic sodium and potassium ion
      concentrations ([Na+]c and [K+]c, respectively), and of the membrane potential
      (Delta c phi) can be attained only, if the flux through the electrogenic Na-K
      pump (JNaK) is balanced electrically, and if JNaK is rather high (about 25% of
      total ATP consumption at 10 mM glucose). Metabolically caused changes of cellular
      pH are unlikely, because, on the one hand, CO2 can rapidly leave the cell through
      cellular membranes, and because ATP cycling cannot produce nor consume protons. A
      slight decrease of pHc during cellular activity is caused mainly by an increased
      Ca-H exchange flux through the plasma membrane Ca2+ pump (J PMCA), which might be
      overcome, however, by H+ transport into secretory granules. The present
      simulations show that the conductance of ATP-sensitive K+ channels (K ATP) is
      highly susceptible to changes of [Mg2+]c. As a physical link between the Ca2+
      filling state of the ER and the initiation of a depolarising, Ca2+ release
      activated current (I CRAN), a metabolite (inositol 1,4,-diphosphate (IP2)) of the
      inositol 1,4,5-triphosphate (IP3) cycle is introduced. Sufficient ATP for insulin
      secretion is made available during glucose activation by [IP2] inhibition of a
      parallel [ATP]c consuming flux through protein biosynthesis (J Pbs). This leads
      to fast oscillations with a triphasic patterns of [Ca2+]c oscillations. Slow
      oscillations are initiated by including a Ca2+ leak current through highly
      uncoupled SERCA3 pumps. Both types of oscillations may superimpose yielding
      compound bursting and mixed oscillations of [Ca2+]c.

PMID- 18321635
TI  - Prediction of the binding modes between BB-83698 and peptide deformylase from
      Bacillus stearothermophilus by docking and molecular dynamics simulation.
AB  - BB-83698 is a first potent inhibitor of peptide deformylase in this novel class
      to enter clinical trials. In this study, automated docking, molecular dynamics
      simulation and binding free energy calculations with the linear interaction
      energy (LIE) method are first applied to investigate the binding of BB-83698 to
      the peptide deformylase from Bacillus stearothermophilus. The lowest docking
      energy structure from each cluster is selected as different representative
      binding modes. Compared with the experimental data, the results show that the
      binding of BB-83698 in Mode 1 is the most stable, with a binding free energy of 
      41.35 kJ/mol. The average structure of the Mode 1 complex suggests that inhibitor
      interacts with Ile59 and Gly109 by hydrogen bond interaction and with Pro47,
      Pro57, Ile59 and Leu146 by hydrophobic interaction are essential for the activity
      of BB-83698. Mode 2 represents a new binding mode. Additionally, if the
      hydrophilic group is introduced to the benzo-[1,3]-dioxole ring, the binding
      affinity of BB-83698 to the peptide deformylase from B. stearothermophilus will
      be greatly improved.

PMID- 18321636
TI  - The role of cultural models in local perceptions of SFM--differences and
      similarities of interest groups from three boreal regions.
AB  - Differences in the way local and regional interest groups perceive Sustainable
      Forest Management in regions with different forest use histories were studied
      using Southeastern Finland, the Mauricie in Quebec and Central Labrador in Canada
      as examples of regions with high, medium and low importance of commercial
      forestry. We present a conceptual model illustrating the cyclic interaction
      between the forest, cultural models about forests and forest management. We
      hypothesized that peoples' perceptions would be influenced by their cultural
      models about forests and would thus vary amongst regions with different forest
      use histories and among different interest groups. The weightings of the
      environmental, economic and social components of sustainability as well as themes
      important for each of the interest groups were elicited using individual listing
      of SFM indicators and group work aimed at developing a consensus opinion on a
      common indicator list. In Southeastern Finland the views of the different groups
      were polarized along the environment-economy axis, whereas in Central Labrador
      all groups were environmentally oriented. The social dimension was low overall
      except among the Metis and the Innu in Labrador. Only environmental groups were
      similar in all three research regions, the largest differences between regions
      were found among the forestry professionals in their weightings concerning
      economy and nature. As the importance of commercial forestry increased, a greater
      importance of economic issues was expressed whereas the opposite trend was
      observed for issues regarding nature. Also inter-group differences grew as the
      importance of commercial forestry increased in the region. Forest management and
      forest use can be seen as factors strongly influencing peoples' cultural models
      on forests.

PMID- 18321637
TI  - Dynamics and mechanism of HSP70 translocation induced by photodynamic therapy
      treatment.
AB  - Heat shock protein 70 (HSP70) is involved in nearly all intracellular
      compartments. It has been recently shown to be expressed on the outer cellular
      membrane under photodynamic therapy (PDT) treatment. However, the mechanism and
      function of HSP70 translocation to the cell surface during PDT treatment are not
      well understood. In this study, the dynamics and mechanism of HSP70 translocation
      onto the cell surface and its relationship with several key intracellular events
      after PDT treatment were investigated using confocal microscopy. HeLa and ASTC-a
      1 tumor cells were treated by PDT using different doses. In the case of PDT
      induced apoptosis, cytoplasmic HSP70 rapidly translocated to the cell surface
      after treatment, but it was not released into the medium. Such translocation was
      found to be dependent on the PDT dose. Moreover, during apoptosis, the
      translocation of HSP70 was closely related to the changes of mitochondrial
      transmembrane potential (DeltaPsim). Under non-lethal PDT induced surface stress,
      HSP70 also translocated to the cell surface, but with a slower rate and a lower
      final surface concentration. These findings reaffirm the HSP70 translocation onto
      the cell surface under PDT treatment in living cells. Our results also indicate
      that the function of the surface expression of HSP70, either initiated by
      mitochondrial disruption or direct surface stress, is to stabilize the plasma
      membrane integrity, although such function failed to prevent apoptosis induced by
      lethal PDT treatment, as evidenced in our study.

PMID- 18321638
TI  - Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio
      Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells.
AB  - Human A3 adenosine receptor (A3AR) agonists showed the anti-tumor activity in
      various in vitro and in vivo studies. The present study investigates the anti
      proliferative effect of a novel adenosine analog 2-chloro-N6-(3-iodobenzyl)-4'
      thioadenosine-5'-N-methyluronamide (thio-Cl-IB-MECA) in A549 human lung cancer
      cells. Thio-Cl-IB-MECA induced arrest of cell cycle progression in G0/G1 phase at
      lower concentrations (up to 20 microM) and apoptotic cell death at a higher
      concentration (80 microM), which were manifested by down-regulation of cyclin D1,
      c-myc, and CDK4, activation of caspase-3 and -9, and cleavage of poly(ADP-ribose)
      polymerase (PARP). The activation of Akt-mediated signaling was also inhibited by
      treatment with thio-Cl-IB-MECA. These data might suggest the potential
      therapeutic value of an adenosine analog in the treatment of human lung cancer.

PMID- 18321639
TI  - Application of novel copolymer-TiO(2) membranes for some textile dyes adsorptive
      removal from aqueous solution and photocatalytic decolorization.
AB  - Novel low density polyethylene-grafted-poly(4-vinylpyridine-co-acrylamide) (LDPE
      g-P(4-VP/AAm)) films were prepared by means of gamma-radiation-induced graft
      copolymerization as support for photocatalytic application. Nanometer-sized
      TiO(2) particles were immobilized to the grafted LDPE via dip coating technique.
      The efficiency of immobilized photocatalyst is tested on two target pollutants
      (textile azo dyes: Remazol red RB-133 (RR RB 133) and reactive blue 2 (RB2)). The
      efficient photocatalytic ability as reflected in determined photobleaching rate
      of both dyes was observed and is comparable to that for the non-supported TiO(2)
      used in a typical slurry photoreactor. The LDPE-g-(4-VP/AAm) copolymers supported
      TiO(2) photocatalyst has the practical advantages of easy separation and removal
      from the polluted environment. It could be a viable technique for the safe
      disposal of textile wastewater into the water streams.

PMID- 18321640
TI  - Polycyclic aromatic hydrocarbons sorption on soils: some anomalous isotherms.
AB  - The sorption of four polycyclic aromatic hydrocarbons (PAHs), namely acenaphthene
      (Ac), phenanthrene (Ph), anthracene (An), and fluoranthene (Fl), on soil has been
      investigated. The kinetics of the sorption is characterised by the presence of
      two distinct periods. A fast initial stage followed by a second slower sorption
      process. Various kinetic models (i.e., Elvoich, Lagergren, second order and
      double exponential models) have been used to fit experimental data. The sorption
      equilibrium of individual PAHs has been assessed in the 298-333 K temperature
      range. Unlike Ac, Ph at 333 K and An and Fl at any temperature showed anomalous
      isotherms. The reason seems to rely on the "trapping" of dissolved PAHs by soil
      organic matter (SOM) released to water. This abnormal trend was not experienced
      when the isotherms were obtained for four PAHs mixture. Apparently, the most
      soluble Ac was capable of binding all the released material so no effect was
      thereafter observed.

PMID- 18321641
TI  - Evaluation of the performance of calix[8]arene derivatives as liquid phase
      extraction material for the removal of azo dyes.
AB  - This paper presents a study on the removal of azo dyes (Reactive Black 5,
      Trapaeolin 000, Methyl Orange and Direct Violet 51) with calix[n]arene
      derivatives from aqueous solution into the organic phase in order to explore the
      potential use of calixarenes as low-cost efficient extractants for wastewater dye
      removal. The carboxylic acid derivative of calix[8]arene shows highest affinity
      towards the azo dyes. The influence of NaCl (present in the solution) on
      extraction process was also studied. The extent of the dye removal increased with
      the addition of NaCl. The proposed extraction mechanism involves several kinds of
      interactions: electrostatic repulsion between carboxylic acid groups of
      calix[8]arenes and sulfonate groups of azo dyes, hydrogen bonding and formation
      of an inclusion complex due to three dimensional cavity type calix[n]arene
      molecules through host-guest interactions.

PMID- 18321642
TI  - Degradation of 2,4-dinitrophenol by combining sonolysis and different additives.
AB  - Based on the effects of various additives on ultrasonic degradation of 2,4
      dinitrophenol (DNP) in aqueous solution, the degradation mechanisms and reaction
      kinetics of DNP in different processes were proposed. The results showed that
      some additives, such as CuO, CCl(4), O(3), NaCl and KI, were favorable for DNP
      sonochemical degradation. On the contrary, DNP degradation efficiency was
      restrained by Na(2)CO(3), indicating that OH radicals oxidation played an
      important role in DNP ultrasonic removal. The significant increases in DNP
      degradation in US/CuO/H(2)O(2), US/CCl(4) and US/O(3) systems were also related
      to the intermediates formed during the reactions, such as HO(2)/O(2)(-) radicals,
      chlorine-containing radicals and HClO. In addition, DNP ultrasonic removal was
      observed to behave as pseudo-first-order kinetics under different experimental
      conditions tested in the present work.

PMID- 18321643
TI  - Removal of aluminum from aqueous solutions by adsorption on date-pit and BDH
      activated carbons.
AB  - The use of a locally prepared date-pit activated carbon and the commercially
      available BDH activated carbon for the removal of trivalent aluminum from aqueous
      solutions was examined at various conditions. In the acidic range of aluminum
      solubility (up to pH value of 4), both adsorbents exhibited maximum (almost
      equivalent) capacities for adsorbing aluminum at the pH value of 4. Date-pit
      activated carbon was more capable of adsorbing traces or low concentrations of
      aluminum ions in the solution. At low initial concentrations of aluminum and low
      pH, the uptake of aluminum using date-pit activated carbon was 0.305 mg/g, while
      that using BDH activated carbon was only 0.021 mg/g. However, the BDH activated
      carbon was more effective in adsorbing aluminum with high concentrations and low
      pH. Furthermore, date-pit activated carbon exhibited higher initial adsorption
      rates as compared to BDH, which showed higher rates at longer periods of time.

PMID- 18321644
TI  - Degradation of gas-liquid gliding arc discharge on Acid Orange II.
AB  - The effects of pH value, initial concentration of dye solution and temperature on
      the degradation efficiency of Acid Orange II (AO7) using gas-liquid gliding arc
      discharge were investigated. The influences of pH value and temperature on
      degradation efficiency were not apparent. Increasing initial solution
      concentration caused the decrease of degradation rate and the increase of
      absolute degradation quantity. Considering energy efficiency and absolute
      degradation quantity, the gas-liquid gliding arc discharge is fit for treating
      high concentration organic wastewater. A possible mineralization pathway was
      proposed through the analysis of intermediate products detected by gas
      chromatograph coupled with mass spectrophotometer (GC-MS) and ion chromatograph
      (IC). Hydroxyl radicals reacted with the azo linkage-bearing carbon of a hydroxy
      substituted ring, leading to the cleavage of -C-N- and degradation of AO7. The
      solution biodegradability was significantly improved (BOD(5)/COD from 0.02 to
      0.43). The toxicity of intermediate products was lower than that of the initial
      Acid Orange II.

PMID- 18321645
TI  - Kinetic studies of elemental mercury adsorption in activated carbon fixed bed
      reactor.
AB  - Activated carbons are suitable materials for Hg(0) adsorption in fixed bed
      operation or in injection process. The fixed bed tests provide good indication of
      activated carbons effectiveness and service lives, which depend on the rates of
      Hg(0) adsorption. In order to correlate fixed bed properties and operation
      conditions, with their adsorptive capacity and saturation time, Hg(0) adsorption
      tests were realized in a bench-scale unit, consisted of F400 activated carbon
      fixed bed reactor. Hg(0) adsorption tests were conducted at 50 degrees C, under
      0.1 and 0.35 ng/cm(3) Hg(0) initial concentrations and with carbon particle sizes
      ranging between 75-106 and 150-250 microm. Based on the experimental breakthrough
      data, kinetic studies were performed to investigate the mechanism of adsorption
      and the rate controlling steps. Kinetic models evaluated include the Fick's
      intraparticle diffusion equation, the pseudo-first order model, the pseudo-second
      order model and Elovich kinetic equation. The obtained experimental results
      revealed that the increase in particle size resulted in significant decrease of
      breakthrough time and mercury adsorptive capacity, due to the enhanced internal
      diffusion limitations and smaller external mass transfer coefficients.
      Additionally, higher initial mercury concentrations resulted in increased
      breakthrough time and mercury uptake. From the kinetic studies results it was
      observed that all the examined models describes efficiently Hg(0) breakthrough
      curves, from breakpoint up to equilibrium time. The most accurate prediction of
      the experimental data was achieved by second order model, indicating that the
      chemisorption rate seems to be the controlling step in the procedure. However,
      the successful attempt to describe mercury uptake with Fick's diffusion model and
      the first order kinetic model, reveals that the adsorption mechanism studied was
      complex and followed both surface adsorption and particle diffusion.

PMID- 18321646
TI  - Vertical distribution of (226)Ra and (210)Po in agricultural soils in Buyuk
      Menderes Basin, Turkey.
AB  - The vertical distribution of (226)Ra and (210)Po was investigated in the
      cultivated soils of the Buyuk Menderes Basin in Turkey. Five soil cores down to a
      depth of about 50 cm were taken from each site and divided into strata of 2-3 cm
      intervals. The samples were analyzed for their (226)Ra and (210)Po activity
      concentrations using radioanalytical methods. Down-core concentration profiles of
      (226)Ra and (210)Po in the soil cores from five sites are obtained. The activity
      concentrations of soil cores range from 80 to 1170 Bq kg(-1) for (226)Ra and from
      10 to 870 Bq kg(-1) for (210)Po with the depth. Analysis of the vertical soil
      profiles indicate that the activity concentrations of (226)Ra and (210)Po for
      soil strata at all the sites have not extremely changed with depth.

PMID- 18321647
TI  - Properties of mutated murine alpha4beta2 nicotinic receptors linked to partial
      epilepsy.
AB  - We characterized, by electrophysiological methods, two biophysical properties of
      murine recombinant alpha4beta2 nicotinic acetylcholine receptors (nAChR) bearing
      a mutation (alpha4:+L264alpha4:beta2 or alpha4:S252Falpha4:beta2) linked to
      autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). Sensitivity to
      acetylcholine (ACh) was increased by the S252F substitution expressed in
      heterozygosis (alpha4:S252Falpha4:beta2) but was markedly reduced when this
      mutation was expressed in homozygosis (S252Falpha4:beta2). ACh sensitivity was
      not altered by the +L264 insertion. Moreover, receptor desensitization was
      significantly increased by both mutations expressed in heterozygosis. These
      results are in general agreement to those of rat and human recombinant receptors
      bearing the same mutations, thus contributing to validate the use of knock-in
      mice harboring ADNFLE mutations as models to study this pathology.

PMID- 18321648
TI  - Increased urban seroprevalence of Toxoplasma gondii infecting swine in Panama.
AB  - Toxoplasmosis gondii causes one of the most common zoonoses worldwide. The rate
      in Panama is one of the highest in the world. Infections are primarily
      asymptomatic in immune competent individuals; however, in immunocompromised
      patient and congenital cases can be lethal. Exposure to the pathogen is
      hypothesized to occur when handling or consuming infected food such as swine
      meat. In this study, we analyzed 290 swine sera collected from six provinces in
      Panama by Indirect Immunofluorescence antibody test (IFAT) against T. gondii.
      Toxoplasma-specific IgG were found in 32.1% of the samples. The highest
      seroprevalence was found in the province of Panama.

PMID- 18321649
TI  - Transmission line matrix modelling of thermal injuries to skin.
AB  - A numerical model based on the transmission line matrix method is presented for
      the quantitative prediction of skin burn resulting from exposure of a specific
      region of human skin surface to a high temperature heat source. Transient
      temperatures were numerically estimated by Pennes' bioheat equation, and the
      damage function denoting the extent of burn was calculated using the Arrhenius
      assumptions for protein damage rate. A two-dimensional transmission line matrix
      model was used to predict the effects of exposure time and structure thicknesses
      on the transient temperature distribution and damage extent. Compared with other
      numerical sources the transmission line matrix results revealed good agreement,
      suggesting that this method may be an effective tool for the thermal diagnostic
      of burns.

PMID- 18321652
TI  - Roles of dorsal column pathway and transient receptor potential vanilloid type 1
      in augmentation of cerebral blood flow by upper cervical spinal cord stimulation
      in rats.
AB  - Clinical and basic studies have indicated that upper cervical spinal cord
      stimulation (cSCS) significantly increases cerebral blood flow (CBF), but the
      mechanisms are incompletely understood. This investigation was conducted to
      differentiate between stimulation of dorsal column fibers and upper cervical
      spinal cord cell bodies in cSCS-induced increases in CBF and decreases in
      cerebrovascular resistance (CVR). cSCS (50 Hz, 0.2 ms, 1 min) was applied on the
      left C1-C2 dorsal column of pentobarbital anesthetized, ventilated and paralyzed
      male rats. Laser Doppler flowmetry probes were placed bilaterally over the
      parietal cortex, and arterial pressure was monitored. cSCS at 30%, 60%, and 90%
      of motor threshold (MT) produced vasodilation bilaterally in cerebral cortices.
      Subsequently, cSCS was applied at 90% MT, and ipsilateral responses were
      recorded. Ibotenic acid (0.3 mg/ml, 0.1 ml) placed on dorsal surface of C1-C2
      (n=7) to suppress cell body activity, did not affect cSCS-induced %DeltaCBF
      (42.5+/-8.1% vs. 36.8+/-7.1%, P>0.05) and %DeltaCVR (-19.4+/-4.2% vs. -15.2+/
      5.6%, P>0.05). However, bilateral transection of the dorsal column at rostral C1
      (n=8) abolished cSCS-induced changes in CBF and CVR. Also, rostral C1 transection
      (n=7) abolished cSCS-induced changes in CBF and CVR. Resinferatoxin (RTX), an
      ultrapotent transient receptor potential vanilloid type 1 (TRPV1) agonist, was
      used to inactivate TRPV1 containing nerve fibers/cell bodies. RTX (2 microg/ml,
      0.1 ml) placed on the C1-C2 spinal cord (n=7) did not affect cSCS-induced
      %DeltaCBF (60.2+/-8.1% vs. 46.3+/-7.7%, P>0.05) and %DeltaCVR (-25.5+/-3.5% vs. 
      21.4+/-8.9%, P>0.05). However, i.v. RTX (2 microg/kg, n=9) decreased cSCS-induced
      %DeltaCBF from 65.0+/-9.5% to 27.4+/-7.2% (P<0.05) and %DeltaCVR from -28.0+/
      7.6% to -14.8+/-4.2% (P<0.05). These results indicated that cSCS-increases in CBF
      and decreases in CVR occurred via rostral spinal dorsal column fibers and did not
      depend upon C1-C2 cell bodies. Also, our results suggested that cerebral but not
      spinal TRPV1 was involved in cSCS-induced cerebral vasodilation.

PMID- 18321653
TI  - Effects of gender and cigarette smoking on reactivity to psychological and
      pharmacological stress provocation.
AB  - We examined the influence of gender and smoking status on reactivity in two human
      laboratory stress paradigms. Participants were 46 (21 men, 25 women) healthy
      individuals who completed the Trier Social Stress Task (i.e., performed speech
      and math calculations in front of an audience) and a pharmacological stress
      provocation (i.e., administration of corticotrophin releasing hormone (CRH))
      after an overnight hospital stay. Approximately half (53%) of the participants
      were smokers. Cortisol, adrenocorticotrophin hormone (ACTH), physiologic measures
      (heart rate, blood pressure), and subjective stress were assessed at baseline and
      at several time points post-task. Men demonstrated higher baseline ACTH and blood
      pressure as compared to women; however, ACTH and blood pressure responses were
      more pronounced in women. Women smokers evidenced a more blunted cortisol
      response as compared to non-smoking women, whereas smoking status did not affect
      the cortisol response in men. Finally, there was a more robust cardiovascular and
      subjective response to the Trier as compared to the CRH. Although preliminary,
      the findings suggest that women may be more sensitive than men to the impact of
      cigarette smoking on cortisol response. In addition, there is some evidence for a
      more robust neuroendocrine and physiologic response to acute laboratory stress in
      women as compared to men.

PMID- 18321654
TI  - Local facilitation of hippocampal metabotropic glutamate receptor-dependent long
      term depression by corticosterone and dexamethasone.
AB  - Long-term potentiation and long-term depression (LTD) of synaptic efficacy, two
      major forms of synaptic plasticity, are believed to underlie learning processes
      and memory storage. We have recently shown that acute stress, through
      corticosterone release and stimulation of glucocorticoid receptors (GRs),
      facilitates the LTD elicited by the group 1 metabotropic glutamate receptor
      (mGluR) agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) in hippocampal CA1
      neurons. However, it is unknown whether sustained corticosterone release, per se,
      is also able to facilitate DHPG-elicited LTD in control (i.e. unstressed)
      conditions, and if so, whether it acts on local (i.e. hippocampal) or distant
      GRs. Here, we show that a brief application of 100 nM corticosterone to rat
      hippocampal slices lowers the threshold for DHPG-elicited LTD, an effect mimicked
      by the local application of the GR agonist dexamethasone. These results show that
      high corticosterone release facilitates hippocampal CA1 mGluR-dependent LTD, and
      does so through local GRs.

PMID- 18321655
TI  - Was the 'Hittite plague' an epidemic of tularemia?

PMID- 18321656
TI  - Significance of hemorrhagic endovasculitis in placentae from stillbirths.
AB  - Hemorrhagic endovasculitis (HEV) is an alteration of fetal chorionic blood
      vessels within the placenta. This disruption of the integrity of the parietal
      blood vessels has been reported in association with poor pregnancy outcomes and
      perinatal complications. In stillbirths, its presence has been implicated as part
      of the mechanism of the cessation of fetal circulation in postmortem retention of
      the placenta. The purpose of this study was to give an interpretation of this
      type of blood vessel damage: whether it is related to the arrest of blood
      circulation after stillbirth, or whether it constitutes an alteration of the
      integrity of placental chorionic circulation contributing to the death of the
      fetus. From 1232 reviewed placentae, we analyzed 46 cases with HEV, 70% from
      livebirths and 30% from stillbirths. The most frequent lesions encountered in
      placentae were categorized microscopically. The distribution of these lesions in
      placentae from livebirth and stillbirth pregnancies was then described. In
      association with HEV, villitis of unknown etiology and chorionic vessel thrombi
      occurred more frequently in placentae from livebirths. Fragmented erythrocytes
      and erythroblasts were more frequent in placentae from stillbirths. Our study
      demonstrates that HEV is more consistently associated with other placental
      lesions in liveborn than in stillborn infants.

PMID- 18321657
TI  - Anticholinesterase and pediculicidal activities of monoterpenoids.
AB  - The repetitive and inadequate application of pediculicidal products frequently
      results in the development of resistance to these compounds. Essential oils are a
      promising alternative to synthetic insecticides, although their mode of action
      remains to be explored. It has been proposed that one possible target of the
      essential oils is the inhibition of acetylcholinesterase (AChE). The role of
      monoterpenoids as possible AChE inhibitors and their relationship with the
      toxicity was investigated both in vitro and in vivo. Inhibition of electric eel
      AChE activity showed that the most effective inhibitor was 1,8-cineole with
      IC(50) 6 x 10(-3) M. The inhibition of AChE activity of head louse homogenate by
      1,8-cineole showed IC(50) 7.7 x 10(-2) M. The intoxication symptoms of head lice
      exposed to vapors of 1,8-cineole was recorded before the in vivo head louse AChE
      inhibition assay. No correlation was found between neurotoxic symptoms and
      inhibition of AChE activity.

PMID- 18321658
TI  - Crototropone, a new tropone derivative from Croton zehntneri.
AB  - Crototropone (3-hydroxy-5,6-dimethoxy-2-methylcyclohepta-2,4,6-trien-1-one) was
      isolated from roots of Croton zehntneri. The structure was established by
      spectroscopic methods.

PMID- 18321659
TI  - Cytotoxic activity of some Asarum plants.
AB  - The cytotoxic activity against some tumor cell lines of 16 commonly used species
      of Asarum was evaluated in this study. All of these plants were widely used in
      Asian countries as traditional medicines or folk medicines. Their inhibitory
      activities against four tumor cell lines (HL-60, BGC-823, KB and Bel-7402) were
      compared. It was observed that 10 of the tested extracts (eight ethanol extracts
      and two water extracts) among 32 extracts of these plants showed cytotoxic
      activity. Those 95% ethanol extractions from A. caudigerellum, A. forbesii, A.
      inflatum and A. maximum exhibited the highest cytotoxic activity, and 95% ethanol
      extracts or water extracts of A. sieboldii var. seoulense, A. himalaicum, A.
      splendens and A. crispulatum showed selective activity against one or two cells
      among the tested tumor cells. This is the first report of Asarum plants
      possessing cytotoxic activity against tumor cell lines.

PMID- 18321660
TI  - Pulsed electromagnetic field at 9.71 GHz increase free radical production in
      yeast (Saccharomyces cerevisiae).
AB  - Potential human health hazards have been reported after exposure to
      electromagnetic fields at low power density. Increased oxidative stress has been
      suggested as a potential mechanism involved in long-term effect of such exposure.
      In the present work, yeast cultures were exposed for 20 min to a 9.71 GHz pulsed
      electromagnetic field at specific absorption rates (SAR) from 0.5 W/kg to 16
      W/kg. Oxidative perturbations were investigated using ESR spin trapping
      experiments and their impacts on membrane fluidity were assessed using spin label
      five nitroxide stearate. The experiments using the water-soluble spin trap alpha
      (4-pyridyl-1-oxide)-N-t-butylnitrone and the lipid-soluble N-tert-butyl-alpha
      phenylnitrone showed an increase of spin adduct production both in low power
      density exposure (SAR<4 W/kg) and in thermal conditions (SAR>4 W/kg). The
      membrane fluidity diminutions after exposure in all the conditions were
      consistent with lipid peroxidation. The overall results suggest an increase of
      the free radical production in the intra cellular compartment; however no effect
      on the yeast vitality was found.

PMID- 18321661
TI  - [Effectiveness and limits of the cleaners steam in hospitals].
AB  - We assessed bactericidal activity of the cleaners steam used for the bio-cleaning
      of the hospital surfaces. We performed of samples (Rodac) before and after use of
      cleaner steam and compared with bactericidal effect of disinfecting detergent
      used in hospital for surfaces. We studied this effectiveness for different time
      of steam contact. Finally, we wanted to prove, by air sampling, that aero-bio
      contamination was possible generated by using cleaners steam. We show that
      bactericidal effect of the cleaner steam is superior of some tested disinfecting
      detergent, for the treatment of one square meter till 2 min. This effectiveness
      diminishes to be just identical in that some disinfecting detergent when use of
      the cleaner steam is up to two or four square meters surfaces till 2 min. On the
      other hand, the cleaner steam is less efficient in terms of bacterial destruction
      when the time of contact steam-soil is superior in 2 min for six square meter
      surface. The air bacterial pollution, generated by the use of the cleaner steam,
      is restricted and not significantly augmented if measured in 44 cm above the soil
      in the course of cleaning. The cleaner steam is indeed a very good equipment for
      the cleaning of surfaces but it is necessary to respect a time of minimal contact
      of 2 min for four square meters surfaces treaties to acquire an antibacterial
      effect at least so important as that acquired with used disinfecting detergent.
      The disinfection of surfaces is then user-dependent and the time of requested
      contact is can be not compatible with hospital obligations.

PMID- 18321662
TI  - [Characterization of hepatitis B virus strains from the Central African Republic:
      preliminary results].
AB  - OBJECTIVES: Genotyping of Hepatitis B virus (HBV) strains from patients in
      Central African Republic and comparison with results obtained in other African
      countries. PATIENTS AND METHODS: Sera were collected from patients admitted with
      symptoms of acute or chronic hepatitis to the "Hopital de l'Amitie de Bangui",
      Central African Republic (CAR). The complete sequence of preS2/S gene has been
      defined for determining genotypes. RESULTS: Hundred and ninety-six sera were
      collected from 112 men and 84 women. Ninety-two percent of patients had contact
      with HBV (anti-HBc postitive) and the HBsAg prevalence was about 62%. HBV DNA was
      detected in 66% of HBsAg positive sera. No HBV-DNA was evidenced among patients
      with negative HBsAg. Ninety-three percent of the HBV strains belonged to genotype
      E; one (3.4%) belonged to genotype A1, and one (3.4%) belonged to genotype D.
      CONCLUSIONS: The high prevalence of HBV infection in the studied population is
      due to their recruitment. The genotype E is predominant in CAR and the intragroup
      variability of HBV genotype E reached only 1.8%. Genotypes A and D were less
      common in CAR their presence may be explained by importation.

PMID- 18321663
TI  - Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene
      expression in human osteoblast cells.
AB  - Runx2 is a Runt domain transcription factor that transcriptionally regulates
      osteoblast differentiation and bone formation. In this study, we show that human
      chondro- and osteosarcoma cell lines, human mesenchymal stem cells (hMSC) and a
      human primary chondrocytes (HC), osteoblst cells (HOb) express an intact isoform
      (RUNX2wt) and 3 alternatively spliced isoforms (RUNX2Delta5, Delta7, and
      Delta5Delta7) that are generated by skipping exon 5 and/or exon 7. Two of the
      truncated forms of RUNX2 (RUNX2Delta5 and RUNX2Delta5Delta7) did not localize in
      the nucleus and had lost their DNA binding activity. In cotransfection
      experiments with an osteocalcin (OC) promoter construct, we confirmed that only
      RUNX2wt and RUNX2Delta7 could upregulate the OC promoter activity in the
      osteosarcoma cell line. In addition, the coactivator CBP/p300 enhanced the
      transcriptional activity of the OC promoter when coexpressed with RUNX2wt or
      RUNX2Delta7, but not when coexpressed with RUNX2Delta5 or RUNX2Delta5Delta7. In
      contrast, the corepressor HDAC3 only repressed the activation from the OC
      promoter when coexpressed with RUNX2wt. These results support the hypothesis that
      RUNX2 both up- and downregulates its target gene promoters, as exemplified by the
      OC gene, using various isoforms and context-dependent formation of
      transcriptional complexes.

PMID- 18321664
TI  - Simple and rapid field tests for brucellosis in livestock.
AB  - Four simple and rapid field tests for the serodiagnosis of brucellosis in cattle,
      goat, sheep and swine were developed. The performance of the assays was
      investigated using serum samples collected in Portugal from animals originating
      from herds with a defined sanitary status with respect to the presence of
      brucellosis. The sensitivity calculated for the bovine, caprine, ovine and swine
      Brucella lateral flow assays based on results obtained for samples collected from
      animals with culture confirmed brucellosis was 90%, 100%, 90% and 73%,
      respectively. None of the samples from animals from herds free of brucellosis
      reacted in the flow assays indicating a high specificity. However, as expected,
      some degree of reactivity was observed when testing selected serum samples that
      reacted non-specific in reference tests for brucellosis.

PMID- 18321665
TI  - Classical swine fever virus strain "C" protects the offspring by oral
      immunisation of pregnant sows.
AB  - The aim of this study was to evaluate if oral immunisation of wild sows protects
      the fetuses from transplacental infection. Two experiments were carried out with
      gilts vaccinated orally with C-strain virus approximately 5 weeks after
      insemination. They were challenged at mid-gestation with highly virulent
      classical swine fever virus (CSFV) or moderately virulent field virus. The
      results revealed that oral vaccination has no negative impact on the pregnancy,
      and all vaccinated sows developed neutralising antibodies. After infection no
      symptoms were detected in the six vaccinated-infected sows. Challenge virus could
      neither be found in blood, nasal and fecal swabs or saliva nor in organs sampled
      at necropsy. Likewise, all fetuses originating from vaccinated sows were
      virologically and serologically negative. In contrast, the controls developed a
      short viremia and as a result of the transplacental infection all fetuses were
      CSFV positive. In addition, 22 serologically positive wild sows of an endemically
      infected area, where oral vaccination had also been carried out, and their
      offspring were free from CSFV or viral RNA. Our results confirm that oral
      immunisation of pregnant wild sows with C-strain vaccine may protect the fetuses
      against CSF.

PMID- 18321666
TI  - Evaluation of neonatal BH4 loading test in neonates screened for
      hyperphenylalaninemia.
AB  - BACKGROUND: The outcome in phenylketonuria is related to the early diagnosis and
      management due to neonatal screening. AIMS: To assess the interest of
      tetrahydrobiopterin (BH4) loading test and phenylalanine hydroxylase (PAH)
      genotyping in the management of neonates with hyperphenylalaninemia (HPA). STUDY
      DESIGN: We evaluate the effectiveness of a BH4 loading test (20 mg/kg) in ten
      neonates screened for HPA. We evaluated the time required to reach a target
      plasma Phenylalanine (Phe) level below 300 micromol/l. We compared these ten BH4
      loaded patients to the 10 previous neonates non-loaded with BH4. In all these
      patients, the PAH genotype was determined. RESULTS: One loaded patient had
      biopterin synthesis deficiency and has been retrieved from statistical analysis.
      All others patients have PAH deficiency. Between the BH4 loaded group (L) and the
      BH4 non-loaded group (NL), a statistically significant difference was observed in
      the average time required to reached the target Phe level (13.56 +/- 4.30 (L) vs.
      20.6 +/- 7.59 days (NL) [p < 0.02]). Results of the genotyping from all but one
      of these 19 patients indicated that among all mutations present in this patient
      population, there were 4 known PAH mutations associated with BH4 responsiveness
      (p.R261Q, the p.V388 M, the p.E390G and the p.Y414C). These mutations were found
      in 4 non-loaded and 6 loaded patients. Two patients had a more than 90% reduction
      in their plasma Phe level within 24 h after the load. One of these patients had a
      PTPS deficiency. The other fully responsive patient (p.Y414C and IVS10-11G>A) has
      been treated with BH4 from birth with an excellent metabolic control for three
      years now. CONCLUSION: BH4 loading test improves the management of HPA. It allows
      an immediate identification of the children fully responsive to BH4. Our results
      therefore suggest the incorporation of BH4 loading test in the management of
      neonates screened for HPA.

PMID- 18321667
TI  - Quantitative expression analysis of Bodhesin genes in the buck (Capra hircus)
      reproductive tract by real-time polymerase chain reaction (qRT-PCR).
AB  - Knowledge of the different patterns of gene expression along the male
      reproductive tract can assist in understanding the physiological processes of
      species-specific reproduction in mammals. In the present work, expression
      profiles of buck spermadhesin (bodhesin) genes along the reproductive tract by
      qRT-PCR were investigated. Total RNA from the seminal vesicle, testis,
      epididymis, bulbourethral gland and ductus deferens were reverse transcribed and
      the cDNA produced was submitted to qRT-PCR. For each homologous bodhesin gene,
      namely Bdh-1, Bdh-2 and Bdh-3, sets of specific primers and recombinant plasmids
      were prepared for gene quantification. In buck seminal vesicles, Bdh-2 is the
      homologue predominantly expressed, with a copy number on the order of millions of
      times more than Bdh-1 and thousand times more than Bdh-3. The copy number of Bdh
      3 mRNA is only 10-fold greater than that of Bdh-1. Bodhesin transcripts were
      detected in all tissues examined, except in ductus deferens. The quantitative
      analysis also demonstrated clearly the differential gene expression of
      spermadhesin in bulbourethral gland. The striking differences in bodhesin gene
      expression indicate that each isoform could have a specific biological function
      in the buck genital tract, which deserves further detailed studies.

PMID- 18321668
TI  - The effects of postnatal FSH substitution on Sertoli cell number and the sperm
      production capacity of the adult boar.
AB  - The role of FSH for Sertoli cell establishment and sperm production in the boar
      is not definitely known. In order to elucidate its function FSH was substituted
      postnatally in male pigs and the resulting effects on testicular histological
      traits and sperm production capacity were investigated when the boars had reached
      maturity. Six male piglets received pFSH from 18 to 48 days postnatally. Another
      six piglets instead received saline and served as controls. Blood samples were
      drawn to measure FSH, LH, testosterone and estradiol. After 28 weeks, the boars
      were trained to mount a dummy so that the spermatogenic capacity was tested by
      increasing the frequency of semen collection at the age of 30 weeks. Libido
      (latency time) and ejaculate criteria (volume, motility, morphological
      abnormalities) were determined. Thereafter the boars were killed and their testes
      analyzed for morphology, number of Sertoli cells, germ cells and Leydig cells as
      well as the ratio between mitosis and apoptosis in the tubules. FSH
      concentrations were twofold due to FSH application when compared to the controls.
      LH was low during the first 2 weeks of FSH treatment. Thereafter concentrations
      increased in three of the six treated animals but not in controls. Testosterone
      increased slightly over the application period both in the controls and the
      treated piglets. Estradiol levels were similar in both groups. Increased
      ejaculation frequency reduced sperm concentrations and sperm motility in all
      boars and the percentage of morphologically abnormal sperm increased. Ejaculate
      volumes and the time of latency were not significantly altered. No differences
      were observed between the controls and the FSH treated boars. The testicular
      parameters of both FSH- and control boars were identical for morphology, number
      of spermatogenic and somatic cells as well as mitosis-apoptosis equilibrium. The
      data demonstrated that a prolonged postnatal period of FSH concentrations does
      not influence the sperm production of the adult boar.

PMID- 18321669
TI  - Chemical method to enhance transungual transport and iontophoresis efficiency.
AB  - Transungual transport is hindered by the inherent small effective pore size of
      the nail even when it is fully hydrated. The objectives of this study were to
      determine the effects of chemical enhancers thioglycolic acid (TGA), glycolic
      acid (GA), and urea (UR) on transungual transport and iontophoresis efficiency.
      In vitro passive and iontophoretic transport experiments of model permeants
      mannitol (MA), UR, and tetraethylammonium (TEA) ion across the fully hydrated,
      enhancer-treated and untreated human nail plates were performed in phosphate
      buffered saline. The transport experiments consisted of several stages,
      alternating between passive and anodal iontophoretic transport at 0.1mA. Nail
      water uptake experiments were conducted to determine the water content of the
      enhancer-treated nails. The effects of the enhancers on transungual
      electroosmosis were also evaluated. Nails treated with GA and UR did not show any
      transport enhancement. Treatment with TGA at 0.5M enhanced passive and
      iontophoretic transungual transport of MA, UR, and TEA. Increasing the TGA
      concentration to 1.8M did not further increase TEA iontophoresis efficiency. The
      effect of TGA on the nail plates was irreversible. The present study shows the
      possibility of using a chemical enhancer to reduce transport hindrance in the
      nail plate and thus enhance passive and iontophoretic transungual transport.

PMID- 18321670
TI  - Optical stimulation of auditory neurons: effects of acute and chronic deafening.
AB  - In developing neural prostheses, particular success has been realized with
      cochlear implants. These devices bypass damaged hair cells in the auditory system
      and electrically stimulate the auditory nerve directly. In contemporary cochlear
      implants, however, the injected electric current spreads widely along the scala
      tympani and across turns. Consequently, stimulation of spatially discrete spiral
      ganglion cell populations is difficult. In contrast to electrical stimulation, it
      has been shown that extremely spatially selective stimulation is possible using
      infrared radiation (e.g. [Izzo, A.D., Su, H.S., Pathria, J., Walsh Jr., J.T.,
      Whitlon, D.S., Richter, C.-P., 2007a. Selectivity of neural stimulation in the
      auditory system: a comparison of optic and electric stimuli. J. Biomed. Opt. 12,
      1-7]). Here, we explore the correlation between surviving spiral ganglion cells,
      following acute and chronic deafness induced by neomycin application into the
      middle ear, and neural stimulation using optical radiation and electrical
      current. In vivo experiments were conducted in gerbils. Before the animals were
      deafened, acoustic thresholds were obtained and neurons were stimulated with
      optical radiation at various pulse durations, radiation exposures, and pulse
      repetition rates. In one group of animals, measurements were made immediately
      after deafening, while the other group was tested at least four weeks after
      deafening. Deafness was confirmed by measuring acoustically evoked compound
      action potentials. Optically and electrically evoked compound action potentials
      and auditory brainstem responses were determined for different radiation
      exposures and for different electrical current amplitudes, respectively. After
      completion of the experiments, the animals were euthanized and the cochleae were
      harvested for histology. Acoustically evoked compound action potential thresholds
      were elevated by more than 40 dB after neomycin application in acutely deaf and
      more than 60 dB in chronically deaf animals. Compound action potential
      thresholds, which were determined with optical radiation pulses, were not
      significantly elevated in acutely deaf animals. However, in chronically deaf
      animals optically evoked CAP thresholds were elevated. Changes correlated with
      the number of surviving spiral ganglion cells and the optical parameters that
      were used for stimulation.

PMID- 18321671
TI  - Frequency and pattern of Chinese herbal medicine prescriptions for chronic
      hepatitis in Taiwan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) has been commonly
      used in treating liver diseases in Asian countries. AIM OF STUDY: To conduct a
      large-scale pharmacoepidemiological study and evaluate the frequency and pattern
      of CHM prescriptions in treating chronic hepatitis. MATERIALS AND METHODS: We
      obtained the database of traditional Chinese medicine outpatient claims from the
      national health insurance in Taiwan for the whole 2002. Patients with chronic
      hepatitis were identified by the corresponding diagnosis of International
      Classification of Disease among claimed visiting files. Corresponding
      prescription files were analyzed, and association rule were applied to evaluate
      the co-prescription of CHM in treating chronic hepatitis. RESULTS: Among the
      91,080 subjects treated by CHM for chronic hepatitis, the peak age was in the 40
      s, followed by 30 s and 50 s. Male/female ratio was 2.07:1. Long-dan-xie-gan-tang
      and Saliva miltiorrhiza (Dan-shen) were the most commonly prescribed Chinese
      herbal formula and single herbal drug, respectively. The most common two-drug
      prescription was Jia-wei-xia-yao-san plus Saliva miltiorrhiza, and the most
      common three-drug prescription was Jia-wei-xia-yao-san plus Saliva miltiorrhiza
      and Artemisia capillaries (Yin-chen-hao). CONCLUSIONS: This study showed the
      utilization pattern of Chinese herbal drugs or formulae in treating chronic
      hepatitis. Further researches and clinical trials are needed to evaluate the
      efficacy of these Chinese herbs or its ingredients in treating chronic hepatitis.

PMID- 18321672
TI  - Nephrogenic system fibrosis: a radiologist's practical perspective.
AB  - This manuscript will provide the background current understanding of Nephrogenic
      Systemic Fibrosis (NSF) necessary to be appreciated by radiologists who are
      practicing cross-sectional imaging including gadolinium based contrast agent (Gd
      CA) enhanced MRI. Examination of the known risk factors for NSF provides a
      practical list of considerations including an appreciation of the degree of
      patient renal function, or dysfunction, and the type and dose of Gd-CA used. Data
      is presented to argue that we must consider not only the one-time dose, but
      particularly the cumulative Gd-CA life-time dose administered to a patient. Using
      the foundation of known risk factors for NSF, we can then assemble a working list
      of strategies that can be utilized in an imaging practice to minimize the risk of
      NSF for all patients, including those at highest risk for this disorder. This
      list includes a discussion of high stability Gd-CAs, cumulative dose monitoring
      and limits, dialysis, and more specific documentation in the medical records.
      Finally, the issues required to understand the information that should be
      provided to the patient prior to obtaining informed consent are discussed. The
      objectives of an informed consent is to ensure that the patient is properly
      informed and involved in the decision to proceed with a contrast enhanced MRI,
      and to provide documentation to establish that the medical facilities and the
      radiologist are themselves well-versed in the risks and benefits when making the
      decision to use contrast enhanced MRI for particular patients. The process of
      informed consent requires that there be a consideration of the risks of not
      performing the contrast enhanced MRI, or the relative risk of performing another
      test, particularly a contrast enhanced CT. This requires an appreciation of the
      risks of CT-related ionizing radiation and cancer, and the risk of iodine based
      contrast agents (I-CA) and contrast induced nephropathy (CIN). Data is presented
      to show that many, and perhaps the vast majority, of renal dysfunction patients
      are at greater risk of harm from I-CA related to CT as compared to high stability
      Gd-CAs used for MRI.

PMID- 18321673
TI  - Hepatic hemangioma: correlation of enhancement types with diffusion-weighted MR
      findings and apparent diffusion coefficients.
AB  - PURPOSE: To correlate hepatic hemangioma enhancement types in gadolinium-enhanced
      magnetic resonance (MR) images with diffusion-weighted MR findings and apparent
      diffusion coefficients (ADCs). MATERIALS AND METHODS: Respiratory-triggered
      diffusion-weighted MR images (TR/TE, 2422/46 ms; parallel imaging factor, 2; b
      factor, 500 s/mm(2); number of averaging, 6) obtained in 35 patients with 44
      hepatic hemangiomas diagnosed by gadolinium-enhanced MR and by follow-up imaging
      were retrospectively evaluated. Hemangiomas were classified into three
      enhancement types based on gadolinium-enhanced MR imaging findings: type I, early
      enhancement type; type II, peripheral nodular enhancement type; type III, delayed
      enhancement type. Two blinded readers qualitatively assessed lesion sizes and
      signal intensities on T2-weighted turbo spin-echo and diffusion-weighted images.
      The ADCs of hemangiomas were also measured. RESULTS: No significant difference
      was observed between the three enhancement types in terms of signal intensities
      on T2-weighted images. Signal intensities on diffusion-weighted images were lower
      in the order type I to III (P<.01), and mean ADCs were 2.18 x 10(-3), 1.86 x 10(
      3), and 1.71 x 10(-3) mm(2)/s for types I, II, and III, respectively (P<.01). No
      correlation was found between lesion sizes and ADCs. CONCLUSION: Hepatic
      hemangiomas were found to have enhancement type dependent signal intensities and
      ADCs on diffusion-weighted MR images. Further studies will have to substantiate
      that these diffusion patterns might reflect intratumoral blood flow or perfusion.

PMID- 18321674
TI  - [Peripheral neuropathy after lumbar plexus block achieved under general
      anesthesia].

PMID- 18321675
TI  - Inter- and intra-individual variability in human skin barrier function: a large
      scale retrospective study.
AB  - In vitro transepidermal tritiated water flux measurements are frequently used to
      evaluate skin barrier integrity for quality control purposes. However, research
      in this area to date has been largely based upon small-scale studies, each
      involving relatively few skin permeation measurements. In order to enhance our
      understanding in this area, we have conducted a much larger scale retrospective
      statistical analysis of tritiated water kp values. These values reflected the
      permeability of 2400 skin samples that were derived from 112 female volunteers
      over a 4 year period. It was found that the population of tritiated water kp
      values constituted a positively skewed, non-Normal distribution. Mean kp was 2.04
      x 10(-3)cm/h while the 95th percentile was 4.50 x 10(-3)cm/h. Both values are
      higher than those reported in previous smaller studies. Hence, our study
      indicates that previously suggested upper limits for tritiated water flux are too
      low and that they be revised upwards to a value of 4.5 x 10(-3)cm/h. Analysis was
      also performed on smaller data subsets allowing inter-individual and intra
      individual comparisons. For intra-individual kp variability, site-related
      differences yielded a non-Normal, positively skewed pattern in most individuals.
      Inter-individual variability was Normally-distributed and showed scatter that was
      much smaller in magnitude.

PMID- 18321676
TI  - Cr (VI) inhibits DNA, RNA and protein syntheses in hepatocytes: involvement of
      glutathione reductase, reduced glutathione and DT-diaphorase.
AB  - In patients with orthopaedic implants, metallic particles have been shown to be
      disseminated widely throughout the body, particularly in the liver, spleen and
      lymph nodes. Levels of metal particles and ions in distant organs were highest in
      patients with loose, corroded prostheses, and when stainless steel and cobalt
      chrome alloy corrode, chromium is released predominantly as Cr (VI), a toxic ion.
      This manuscript investigates the interaction of Cr (VI) with liver cells in terms
      of inhibition of macromolecular synthesis, and the contribution of reduced
      glutathione (GSH), DT-diaphorase and glutathione reductase (GRd) to the toxicity
      of Cr (VI). Cr (VI) caused concentration dependent inhibition of protein, DNA and
      RNA synthesis in hepatocytes. GRd and to a lesser extent DT-diaphorase activities
      were involved in the generation of toxic intermediates. GRd activity was markedly
      inhibited during the reduction of Cr (VI), and GSH levels decreased. The
      concentrations of Cr (VI) found to inhibit macromolecular syntheses in this study
      are clinically relevant: it is therefore important to develop implants with
      minimum wear potential.

PMID- 18321677
TI  - Genotoxicity of thimerosal in cultured human lymphocytes with and without
      metabolic activation sister chromatid exchange analysis proliferation index and
      mitotic index.
AB  - Thimerosal is an antiseptic containing 49.5% of ethyl mercury that has been used
      for years as a preservative in many infant vaccines and in flu vaccines.
      Thimerosal is an organic mercurial compound used as a preservative in biomedical
      preparations. In this study, we evaluated the genotoxic effect of thimerosal in
      cultured human peripheral blood lymphocytes using sister chromatid exchange
      analysis in culture conditions with and without S9 metabolic activation. This
      study is the first report investigating the genotoxic effects of thimerosal in
      cultured human peripheral blood lymphocyte cells using sister chromatid exchange
      analysis. An analysis of variance test (ANOVA) was performed to evaluate the
      results. Significant induction of sister chromatid exchanges was seen at
      concentrations between 0.2 and 0.6 microg/ml of thimerosal compared with negative
      control. A significant decrease (p<0.001) in mitotic index (MI) and proliferation
      index (PRI) as well as an increase in SCE frequency (p<0.001) was observed
      compared with control cultures. Our results indicate the genotoxic and cytotoxic
      effect of TH in cultured human peripheral blood lymphocytes at tested doses in
      cultures with/without S9 fraction.

PMID- 18321678
TI  - Psychological distress, killer lymphocytes and disease severity in HIV/AIDS.
AB  - Immunocellular mechanisms that account for the association between psychosocial
      risk factors and increased susceptibility to faster progression of HIV/AIDS are
      largely unknown. This study used structural equation modeling to test the
      hypothesis that enumerative and functional alterations in killer lymphocytes
      mediate the relationship between higher levels of psychological distress (defined
      by perceived stress, anxiety and depressive symptoms) and greater HIV disease
      severity (defined by HIV-1 viral load and T-helper (CD4(+)) cell count),
      independent of standard demographic and various HIV-related covariates.
      Participants were 200 HIV-1 seropositive adults on combination antiretroviral
      therapy (ages 20-55 years; 67% men; 62% black; 84% AIDS). The data fit a
      psychoimmune model in which the significant relationship between higher distress
      levels and greater disease severity was mediated by diminished natural killer
      (NK) cell count and cytotoxic function, as well as increased cytotoxic (CD8(+)) T
      cell activation. Overall the findings indicated that the psychoimmune model
      accounted for 67% of the variation in HIV disease severity. In contrast, the data
      did not support a reverse directionality mediation model, where greater HIV
      disease severity predicted greater distress as a function of killer lymphocyte
      status. In sum, the psychoimmune associations of the final model are
      physiologically consistent and suggest that distress-related alterations in
      killer lymphocyte immunity may play a role in the biobehavioral mechanisms linked
      with HIV-1 pathogenesis.

PMID- 18321679
TI  - Transform your data.

PMID- 18321680
TI  - Electrophysiological basis for the ability of olanzapine to improve verbal memory
      and functional outcome in patients with schizophrenia: a LORETA analysis of P300.
AB  - Abnormality of P300 waveforms of event-related potentials (ERPs) has been
      suggested to represent an aspect of the pathophysiology of schizophrenia.
      Previous work points to the contribution of altered neural function in discrete
      brain regions in the left hemisphere to psychotic symptoms and cognitive deficits
      of schizophrenia. In this study, we sought to determine: 1) if patients with
      schizophrenia elicit a decreased P300 current source density in brain areas, such
      as the superior temporal gyrus (STG); 2) if decreased P300 generator density in
      the left STG is recovered by treatment with the most widely-used antipsychotic
      drug olanzapine; and 3) if the recovery of P300 source density is associated with
      improvements of cognitive and functional status. P300 in response to an auditory
      oddball task, as well as verbal learning memory, psychopathology, and quality of
      life were evaluated in 16 right-handed patients with schizophrenia before and
      after treatment with olanzapine for 6 months. ERP data were also obtained from 16
      right-handed age and gender-matched normal volunteers. Low resolution
      electromagnetic tomography (LORETA) analysis was used to obtain current density
      images of P300. Patients with schizophrenia showed significantly smaller LORETA
      values in several brain regions in the left side, particularly STG, middle
      frontal gyrus, and precentral gyrus, compared with control subjects. Six-month
      treatment with olanzapine significantly increased P300 source density only in the
      left STG. Positive symptoms, negative symptoms, verbal learning memory, and
      quality of life were also improved during treatment. Significant correlations
      were found between the increase in LORETA values of left STG vs. improvements of
      negative symptoms, as measured by Scale for the Assessment of the Negative
      Symptoms, and verbal learning memory, as measured by the Japanese Verbal Learning
      Test. Improvement of quality of life, as evaluated by the Quality of Life Scale,
      were significantly associated with an increase in LORETA values of middle frontal
      gyrus, and tended to correlate with that of precentral gyrus. The results of this
      study suggest that changes in cortical activity, as measured by ERPs, are
      responsible for the ability of some antipsychotic drugs to improve cognition and
      functional outcome in patients with schizophrenia.

PMID- 18321681
TI  - Multilocus sequence identification of Penicillium species in cork bark during
      plank preparation for the manufacture of stoppers.
AB  - Despite several studies reporting Penicillium as one of the most frequent fungal
      genera in cork planks, the isolates were rarely identified to species level. We
      conducted a detailed study to identify Penicillium species from the field to the
      factory environment prior to and after boiling the cork planks. A total of 84
      samples were analyzed. Of the 486 Penicillium isolates phenotypically identified,
      32 representative or unusual strains were selected for identification by
      multilocus DNA sequence type. Cork proved to be a rich source of Penicillium
      biodiversity. A total of 30 taxa were recognized from cork including rarely seen
      species and 6 phylogenetically unique groups. Spores of some species lodged deep
      in cork can survive the boiling process. P. glabrum, P. glandicola and P.
      toxicarium, species with high CFU numbers in the field, are still frequently
      present in cork after boiling. Other species are killed by the boiling treatment
      and replaced by Penicillium species originating from the factory environment.
      Species known to contribute to cork taint were isolated at all stages. Good
      manufacturing practices are necessary at all stages in the preparation of cork
      planks to minimize the load of Penicillium species that produce cork taint.

PMID- 18321682
TI  - Indole derivatives as efflux pump inhibitors for TolC protein in a clinical drug
      resistant Escherichia coli isolated from a pig farm.

PMID- 18321683
TI  - Direct electron-transfer of myoglobin within a new zwitterionic gemini surfactant
      film and its analytical application for H2O2 detection.
AB  - The direct electron-transfer of myoglobin in a new zwitterionic gemini surfactant
      film with glassy carbon electrode surface has been investigated. A pair of well
      defined and quasi-reversible voltammetric peaks was observed at -0.34 and -0.30 V
      due to the direct electron-transfer of the redox couple of Mb (Fe(III)/Fe(II)).
      The voltammetric responses of myoglobin-surfactant film under different pH and
      scan rate conditions were obtained. The presence of hydrogen peroxide changed the
      typical electrochemical behaviors in terms of bioelectrocatalysis of myoglobin to
      hydrogen peroxide, and a higher sensitive electroanalytical method for the
      determination of hydrogen peroxide has been developed.

PMID- 18321684
TI  - Biosorption of lead(II) from aqueous solutions by non-living algal biomass
      Oedogonium sp. and Nostoc sp.--a comparative study.
AB  - Industrial wastewaters containing heavy metals pose a major environmental problem
      that needs to be remedied. The present study reports the ability of two non
      living (dried) fresh water algae, Oedogonium sp. and Nostoc sp. to remove
      lead(II) from aqueous solutions in batch system under varying range of pH (2.99
      7.04), contact time (5-300 min), biosorbent dose (0.1-0.8 g/L), and initial metal
      ion concentrations (100 and 200mg/L). The optimum conditions for lead biosorption
      are almost same for the two algal biomass Oedogonium sp. and Nostoc sp. (pH 5.0,
      contact time 90 and 70 min, biosorbent dose 0.5 g/L and initial Pb(II)
      concentration 200mg/L) however, the biomass of Oedogonium sp. was found to be
      more suitable than Nostoc sp. for the development of an efficient biosorbent for
      the removal of lead(II) from aqueous solutions, as it showed higher values of
      q(e) adsorption capacity (145.0mg/g for Oedogonium sp. and 93.5mg/g for Nostoc
      sp.). The equilibrium data fitted well in the Langmuir isotherms than the
      Freundlich isotherm, thus proving monolayer adsorption of lead on both the algal
      biomass. Analysis of data shows that the process involves second-order kinetics
      and thermodynamic treatment of equilibrium data shows endothermic nature of the
      adsorption process. The spectrum of FTIR confirms that the amino and carboxyl
      groups on the surface of algal biomass were the main adsorption sites for lead
      removal. Both the biosorbents could be regenerated using 0.1 mol/L HCl solution,
      with upto 90% recovery. The biosorbents were reused in five biosorption
      desorption cycles without a significant loss in biosorption capacity. Thus, this
      study demonstrated that both the algal biomass could be used as an efficient
      biosorbents for the treatment of lead(II) bearing wastewater streams.

PMID- 18321685
TI  - Differential adsorption of variants of the Thermomyces lanuginosus lipase on a
      hydrophobic surface suggests a role for local flexibility.
AB  - Lipases are activated at interfaces between aqueous and hydrophobic phases, where
      they typically undergo conformational changes leading to significant activity
      increase. Here I use a quartz crystal microbalance with dissipation (QCM-D) to
      study changes in layer thickness and viscosity during the adsorption of variants
      of the Thermomyces lanuginosus lipase (TlL) onto a methyl-terminated hydrophobic
      surface. Unlike wildtype TlL, the variant Mut1, which shows improved performance
      under certain test conditions, shows a large dissipation increase during the
      binding process, leading to a significantly thicker layer. This altered
      adsorption behaviour may be linked to Mut1's changes in secondary structure. This
      is corroborated by the fact that four other TlL mutants with unaltered secondary
      structure showed wildtype-like absorption behaviour. Unlike wildtype TlL and the
      other variants, Mut1 contains several consecutive basic residues introduced into
      the C-terminal region which is close in space to the N-terminal part of the
      protein, which also contains several basic residues. Electrostatic repulsion
      between these two regions leading to local structural flexibility may facilitate
      altered adsorption behaviour and ultimately to improved enzymatic performance on
      a solid surface. QCM-D thus provides a good approach to screen protein variants
      for their adsorption properties on hydrophobic surfaces.

PMID- 18321686
TI  - In vivo evaluation of a transdermal codrug of 6-beta-naltrexol linked to
      hydroxybupropion in hairless guinea pigs.
AB  - 6-Beta-naltrexol is the major active metabolite of naltrexone, NTX, a potent mu
      opioid receptor antagonist used in the treatment of alcohol dependence and opioid
      abuse. Compared to naloxone, NTX has a longer duration of action largely
      attributed to 6-beta-naltrexol. This study was carried out in order to determine
      percutaneous absorption of a transdermal codrug of naltrexol, 6-beta-naltrexol
      hydroxybupropion codrug (CB-NTXOL-BUPOH), in hairless guinea pigs as well as to
      evaluate the safety of 6-beta-naltrexol for development as a transdermal dosage
      form. This codrug may be useful in the simultaneous treatment of alcohol
      dependence and tobacco addiction. The carbonate codrug traversed the skin at a
      faster rate than 6-beta-naltrexol. 6-Beta-naltrexol equivalent steady state
      plasma concentrations of 6.4 ng/ml were obtained after application of the codrug
      as compared to 1.2 ng/ml from 6-beta-naltrexol base. The steady state plasma
      concentration of hydroxybupropion after codrug application was 6.9 ng/ml. Skin
      sensitization and irritation tested in the hairless guinea pigs using the Buehler
      method revealed that 6-beta-naltrexol had no skin sensitizing potential. The
      method was validated with a known sensitizer, p-phenylenediamine, which induced
      sensitization in 90% of the animals. 6-beta-Naltrexol caused only mild transient
      skin irritation after the initial application of the patch. During subsequent
      applications, erythema was slightly increased but no skin damage was observed. In
      conclusion, a transdermal codrug of 6-beta-naltrexol could be a viable
      alternative treatment for alcohol and opiate abuse.

PMID- 18321687
TI  - [Disseminated nocardiosis in a child with acute lymphoblastic leukemia].
AB  - Nocardiosis is a rare infectious disease in children. We report here a
      disseminated nocardiosis in a child with acute lymphoblastic leukemia. The
      patient presented prolonged febrile neutropenia and nodular pneumopathy. Based on
      the amplification of a 16S rDNA, a PCR assay detected Nocardia sp. in the
      patient's bronchoalveolar lavage (BAL) fluid. Culture of BAL samples yielded
      Nocardia nova colonies after 2 weeks of incubation. Hepatic, splenic, renal and
      cerebral localisations were detected on extension checkup. trimethoprime
      sulfamethoxazole and amikacine were started given the results of PCR assay, with
      a good response. Improvement of the patient's general condition led to complete
      chemotherapy under ciprofloxacine and ceftriaxone treatment, without nocardiosis
      reactivation. Nocardiosis is a rare complication in children with acute
      lymphoblastic leukemia. trimethoprime-sulfamethoxazole prophylaxis is widely used
      to prevent Pneumocystis jiroveci infection in children with haematologic
      malignancies. As Nocardia species are usually sensible, trimethoprime
      sulfamethoxazole could play a role in Nocardia prophylaxis in such population. In
      our patient, compliance with trimethoprime-sulfamethoxazole had been low.
      Nocardia species are relatively fastidious growth bacteria and are difficult to
      isolate with classical bacteriological techniques. Molecular methods are now
      available, with a good sensitivity and fast results allowing to start an
      appropriate antibiotherapy before culture results, as early treatment is a major
      prognosis factor in nocardiosis. Nocardia infection should be suspected in case
      of nodular pneumopathy in immunocompromised children. An extension checkup should
      be performed to detect secondary localisations.

PMID- 18321688
TI  - [Chikungunya in paediatrics: epidemic of 2005-2006 in Saint-Denis, Reunion
      Island].
AB  - During the southern-hemispheric 2005-2006 summer, Reunion Island was struck by an
      epidemic of Chikungunya (Chik), which affected more than a third of the overall
      population. OBJECTIVES: Our objective was to describe pediatric cases of Chick.
      MATERIAL AND METHODS: We conducted a retrospective descriptive monocentric study
      of confirmed pediatric cases of Chik recruited at Saint-Denis' departmental
      hospital during the peak of the epidemic (January 1st to April 30th 2006).
      RESULTS: Eighty-six children aged 10 days to 18 years were included. In addition
      to the typical clinical presentation, we observed other phenotypes. Well-known
      complicated forms with neurologic, cardiac, gastro-intestinal (plus dehydration)
      involvement were thoroughly investigated using modern medical technology. We
      observed 2 fatal cases of acute disease in 9-year-old children: death resulted
      from a central nervous system insult in one case, and multisystemic neurological,
      cardiac, haemorrhagic involvement in another. Severe acute presentations
      requiring hospital admission involved mainly children aged less than 6 months,
      and those with cardiac, skin and neurologic impairment. The study identified 3
      cases of epidermolysis bullosa, which to our knowledge, have never been described
      previously. CONCLUSION: Chik in children warrants further research in order to
      propose early and appropriate treatments to avoid complications.

PMID- 18321689
TI  - [Risk announcement in paediatric cancerology: strengthen the therapeutic
      alliance].
AB  - Although announcement of the risks related to treatment has become a general rule
      in the healthcare relationship, doctors, nurses and parents of severely ill
      children tend to feel uncomfortable in relation to this mandatory information.
      The work conducted by the AP-HP Espace ethique working party in collaboration
      with parents, healthcare personnel and a philosopher demonstrates the need to
      announce these risks, even beyond the legal framework, while bearing in mind the
      difficulties and hazards inherent to changes in legislation and by observing the
      philosophical values that subtend this legislation. Faced with the broad range of
      diverse and complex risks, the working party proposes a classification of risks
      and hierarchisation of the difficulties encountered by the doctor during this
      announcement, which is difficult to make, and difficult to hear, as intimately
      related to the child's quality of life. The very concept of the probability of a
      risk raises concepts that are difficult to accept: chance, randomness, and
      uncertainty. Informing the patient involves hearing as much as talking, listening
      as much as explaining and requires availability, time, space and an ability to
      listen to the patient. This article proposes several good practice guidelines
      designed to consolidate the therapeutic alliance by sharing the uncertainty of
      the risk and allowing the various partners to remain actors. Nonconfiscation of
      knowledge by doctors does not lead to a loss or transfer of their responsibility,
      but allows decisions to be taken in the context of the alliance, while taking the
      risks into account.

PMID- 18321690
TI  - [Out-of-hospital cardiac arrest in children with bacterial tracheitis].
AB  - Bacterial tracheitis is a severe cause of acute infectious upper-airway
      obstruction. Its characteristics include thick purulent secretions with or
      without plaques or pseudomembrane formation. Fatal complications are infrequent
      if an appropriate treatment is conducted. CASE REPORT: We report on 2 cases of
      bacterial tracheitis revealed by out-of-hospital cardiac arrest. At presentation
      in winter, both children first had the symptoms of viral croup. However, no
      response to the appropriate therapy for this disease was observed. A cardiac
      arrest occurred on the second day. Bronchoscopy allowed diagnosis. Findings on
      initial examination were erythema, edema and purulent secretions. Bacterial
      cultures of tracheal secretions were positive with Staphylococcus aureus.
      Serology with influenza A virus was also positive. Despite antibiotics and
      mechanical ventilation, both children died in the pediatric intensive care unit,
      consecutively to irreversible ischemic brain injury. CONCLUSION: Bacterial
      tracheitis remains a life-threatening upper-airway infection. Prompt recognition
      and accurate diagnosis could lead to decreased mortality. It is essential to
      reassess any croup whose outcome is not rapidly favourable. Such patients should
      be monitored in a pediatric intensive care unit.

PMID- 18321691
TI  - [Chronic disease and childhood: image of the body, psychic stakes and therapeutic
      alliance].
AB  - The child is an individual in constant development, dependent on his/her parents
      with whom he interacts everyday to open out, and in particular, to construct a
      dependable image of his body for growing up comfortably. Announcement of a
      disease, real traumatism for the whole family, upsets these exchanges and can
      often induce psychological difficulties masked by the therapeutic somatic stakes
      placed at the foreground of concerns of each one: child, parents and doctors. The
      child's stakes are construction of a good image of the body (basis of his own)
      which can be deteriorated by the disease whatever it is (chronic disease, with
      relapse or vital prognosis engaged). The family's stakes are the perception of
      the disease by the parents (distress, culpability, depression) and sibling's
      reactions (aggressiveness, identification with the sick child, masked depression,
      functional troubles). Doctor's stakes in the chronic disease is to obtain
      therapeutic alliance of the child and his family to allow the good progress of
      the treatments. In front of the chronic disease's reality, it is essential to
      establish and maintain a multidisciplinary follow up. The child's psychiatrist
      role will be to take care of the exchanges, and listening among the doctors, the
      patient and his family are favoured.

PMID- 18321692
TI  - [Tolerance and efficacy of atovaquone-proguanil for the treatment of paediatric
      imported Plasmodium falciparum malaria in France: clinical practice in a
      university hospital in Paris].
AB  - Only few drugs for uncomplicated Plasmodium falciparum malaria are available in
      children. Atovaquone-proguanil is a recent antimalarial drug licensed in France
      for the uncomplicated P. falciparum malaria in adults. Few paediatric studies
      have evaluated atovaquone-proguanil in children for uncomplicated malaria in
      endemic area, but no study have evaluated this treatment for imported malaria.
      OBJECTIVE: To evaluate treatment by atovaquone-proguanil for uncomplicated and
      imported P. falciparum malaria in children. METHODS: We retrospectively evaluated
      the tolerance and the efficacy of atovaquone-proguanil in the children admitted
      in Robert-Debre Hospital (Paris) for a P. falciparum malaria. From January 2004
      to December 2005, 48 children with a median age of 7,5 years (IQR 4-11) were
      treated with atovaquone-proguanil for a uncomplicated P. falciparum malaria,
      except for 5 children who had an isolated hyperparasitemia greater or equal to
      5%. RESULTS: Atovaquone-proguanil was stopped for 3/48 children because of
      vomiting. Fever resolved in all the children between Day 3 and 7, following the
      beginning of the treatment. One child, with a favourable outcome, had a positive
      parasitemia at Day 4 equal to the initial parasitemia (0,1%). No late therapeutic
      failure was observed among the 24 children evaluated up to one month after
      starting treatment. CONCLUSION: Atovaquone-proguanil is an efficient and well
      tolerated antimalarial treatment for uncomplicated P. falciparum malaria in
      children. The risk of vomiting should lead to a systematic initial
      hospitalisation of children treated with atovaquone-proguanil.

PMID- 18321693
TI  - Postprandial chylomicrons and adipose tissue lipoprotein lipase are altered in
      type 2 diabetes independently of obesity and whole-body insulin resistance.
AB  - BACKGROUND AND AIMS: Postprandial lipoprotein abnormalities in type 2 diabetes
      are associated with insulin resistance. The role of other diabetes-related
      factors is still not clear. The aim of this study is to differentiate the effects
      of whole-body insulin resistance, obesity, and type 2 diabetes on postprandial
      dyslipidaemia and lipoprotein lipase (LPL) in adipose tissue. METHODS AND
      RESULTS: Ten subjects with obesity and diabetes (OD), 11 with obesity alone (O),
      and 11 normal-weight controls (C) - males, aged 26-59 years, with fasting normo
      triglyceridaemia underwent measurements of cholesterol, triglycerides, apo B-48
      and apo B-100 concentrations in plasma lipoproteins separated by density gradient
      ultracentrifugation before and after a fat-rich meal. Fasting and postprandial
      (6h) LPL activity was determined in abdominal subcutaneous adipose tissue biopsy
      samples. Insulin sensitivity was measured by hyperinsulinaemic euglycaemic clamp.
      OD and O subjects had similar degrees of adiposity (BMI, waist circumference, fat
      mass) and insulin resistance (insulin stimulated glucose disposal and M/I). They
      also showed a similarly higher postprandial increase in large VLDL lipids
      (triglyceride incremental AUC 188+/-28 and 135+/-22 mg/dl.6h) than C (87+/-13
      mg/dl.6h, M+/-SEM, p<0.05). OD had an increased chylomicron response compared to
      O (triglyceride incremental AUC 132+/-23 vs. 75+/-14 mg/dl.6h, p<0.05). OD had
      significantly lower fasting and postprandial adipose tissue heparin-releasable
      LPL activity than O and C. CONCLUSIONS: In insulin-resistant conditions of
      obesity, with and without diabetes, large VLDL are increased after a fat-rich
      meal. In addition, diabetic patients compared to obese subjects have an increased
      postprandial chylomicron response and a reduced adipose tissue LPL activity.

PMID- 18321694
TI  - Antiplasmodial and antitrypanosomal activity of Triclisia sacleuxii (Pierre)
      Diels.
AB  - The antiplasmodial and antitrypanosomal activities of Triclisia sacleuxii
      (Pierre) Diels were investigated on three Plasmodium falciparum strains [FcB1,
      3D7 (chloroquine-sensitive) and W2 (chloroquine-resistant) strains] and on
      Trypanosoma brucei Tbsf 221. Roots, stems and leaves ethanolic extracts as well
      as crude tertiary and quaternary alkaloids fractions were considered. Whereas the
      ethanolic extracts and quaternary crude alkaloids fractions exhibited no
      significant activity, the roots and stems tertiary alkaloid fractions revealed
      interesting growth inhibition against the Plasmodium FcB1 and Trypanosoma Tbsf
      221 strains. The IC(50) were 1.04 and 0.89 microg/ml for roots, 2.50 and 0.91
      microg/ml for stems. The leaves tertiary alkaloids fraction also showed a
      promising antitrypanosomal activity (IC(50): 1.85 microg/ml). Phytochemical
      analysis of the roots tertiary alkaloids fraction yielded four major compounds,
      phaeanthine, N-methylapateline, 1,2-dehydroapateline and 1,2-dehydrotelobine,
      which were identified on the basis of their spectroscopic data. The four
      compounds displayed (in vitro) antitrypanosomal activity with IC(50) of 2.68,
      1.19, 1.06 and 1.11 microM, respectively. They also demonstrated antiplasmodial
      activity on Plasmodium falciparum 3D7, with IC(50) of 1.72, 0.93, 1.39 and 12.4
      microM respectively and on the chloroquine-resistant W2 with IC(50) of 0.35,
      1.10, 1.63 and 1.52 microM.

PMID- 18321695
TI  - The rust mycobiota of southern Africa: species richness, composition, and
      affinities.
AB  - The rust mycobiota (Uredinales, Basidiomycota) of southern Africa (Botswana,
      Namibia, and South Africa) is analysed with regard to species richness, generic
      composition, and similarities to the rust mycobiotas of the remaining African
      continent and other regions of the world. Southern Africa is home to about 546
      rust species: ca 522 species have been reported from South Africa, 73 from
      Namibia, and less than ten from Botswana. Thirty-two species were considered to
      be exotics. Two hundred and twenty-five of the species are restricted to southern
      Africa, suggesting an endemism rate of ca 44%. At present, the rust fungus:host
      ratio is 1:38.5, which is much lower than expected from other regions of the
      world. This low ratio may partly be due to under-exploration of the area, but the
      results presented here indicate that a natural paucity of rust fungi on certain,
      especially species-rich plant taxa centred in southern Africa and possibly
      environmental factors are more important reasons. The predominant genera are
      Puccinia and Uromyces accounting for ca 59% of the rust species. The genera
      Hemileia, Phakopsora and especially Ravenelia, centred in tropical regions, are
      well represented and sum up to 8% of the species. Members of Melampsoraceae and
      Phragmidiaceae, common in temperate regions of the Northern Hemisphere, are
      scarce. Most of the other 28 recorded teleomorph genera are only represented by
      three or less species. In an African context, most species are shared with
      central and east Africa (almost 16%). Only a few species are disjunct between
      southern and West Africa or Madagascar. Ca 10% of the species are shared only
      with other parts of the paleotropics, especially the Indian subcontinent.
      Disjunctions of native species with the New World, Australia/New Zealand, or
      Europe are rare.

PMID- 18321696
TI  - Prevalence of inflammatory bowel disease in patients with airways disease.
AB  - BACKGROUND: Case reports and case series have suggested an association between
      inflammatory bowel disease (IBD) and airways disease, but there are no data
      demonstrating a higher prevalence of IBD among patients with airways disease.
      Furthermore, no consistent radiological, pulmonary or pathological abnormalities
      have been demonstrated in patients with both conditions. AIMS: To determine the
      prevalence of IBD among patients with airways disease and to evaluate clinical
      and pathophysiological features. METHODS: A retrospective analysis of outpatients
      with airways disease over a 10-year period. RESULTS: IBD was four times more
      prevalent among patients with airways disease compared with published local IBD
      prevalence [Odds Ratio 4.26, 95% CI 1.48, 11.71, p=0.006; Crohn's disease OR
      5.96, 95% CI 1.94, 18.31, p=0.002 and ulcerative colitis OR 4.21, 95% CI 1.71,
      10.41, p=0.001]. IBD was more frequent in all types of airways disease except
      asthma; the association was particularly strong for conditions associated with
      productive cough. All except 1 patient had established IBD before the onset of
      respiratory symptoms. There were no obvious radiological differences between
      ulcerative colitis and Crohn's disease cases. There was a trend for a higher
      lymphocyte count (despite a tendency to lower blood lymphocyte count) but lower
      sputum neutrophil count in patients with Crohn's disease compared with ulcerative
      colitis. There were no significant differences in physiological measurements of
      pulmonary function between the two types of IBD. CONCLUSION: Our findings support
      an association between airways disease and inflammatory bowel disease,
      particularly non-asthmatic airways disease with productive cough.

PMID- 18321697
TI  - Sequential extraction of metals from mixed and digested sludge from aerobic WWTPs
      sited in the south of Spain.
AB  - The content of heavy metals is the major limitation to the application of sewage
      sludge in soil. However, assessment of the pollution by total metal determination
      does not reveal the true environmental impact. It is necessary to apply
      sequential extraction techniques to obtain suitable information about their
      bioavailability or toxicity. In this paper, sequential extraction of metals from
      sludge before and after aerobic digestion was applied to sludge from five WWTPs
      in southern Spain to obtain information about the influence of the digestion
      treatment in the concentration of the metals. The percentage of each metal as
      residual, oxidizable, reducible and exchangeable form was calculated. For this
      purpose, sludge samples were collected from two different points of the plants,
      namely, sludge from the mixture (primary and secondary sludge) tank (mixed
      sludge, MS) and the digested-dewatered sludge (final sludge, FS). Heavy metals,
      Al, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Ti and Zn, were extracted following
      the sequential extraction scheme proposed by the Standards, Measurements and
      Testing Programme of the European Commission and determined by inductively
      coupled plasma atomic emission spectrometry. The total concentration of heavy
      metals in the measured sludge samples did not exceed the limits set out by
      European legislation and were mainly associated with the two less-available
      fractions (27-28% as oxidizable metal and 44-50% as residual metal). However,
      metals as Co (64% in MS and 52% in FS samples), Mn (82% in MS and 79% in FS), Ni
      (32% in MS and 26% in FS) and Zn (79% in MS and 62% in FS) were present at
      important percentages as available forms. In addition, results showed a clear
      increase of the concentration of metals after sludge treatment in the proportion
      of two less-available fractions (oxidizable and residual metal).

PMID- 18321698
TI  - The best utilization of D. zingiberensis C.H. Wright by an eco-friendly process.
AB  - An eco-friendly process for the best utilization of D. zingiberensis C.H. Wright
      tubers was developed. In the first stage, cellulose and ethanol were recovered by
      physical separation, multi-enzymes hydrolysis with yeast fermentation, and in the
      second stage diosgenin was separated using ethanol-modified supercritical carbon
      dioxide extraction. The new approach could not only recover 95% of diosgenin
      production, 95% of ethanol and 75% of cellulose, but also efficiently reduce 88%
      of COD in wastewater compared with the conventional method, which only extract
      diosgenin with discharging 80,000mg/l of COD into public sewers. The research
      indicates that the proposed system could be a clean and technological-efficient
      alternative to conventional processing of D. zingiberensis C.H. Wright tubers in
      industry.

PMID- 18321699
TI  - Start-up of an UASB-septic tank for community on-site treatment of strong
      domestic sewage.
AB  - Two community on-site UASB-septic tanks were operated in parallel over a six
      months period under two different hydraulic retention times (HRT) of 2 days for
      R1 and 4 days for R2 at mean sewage temperature of 24 degrees C. The sewage was
      characterised by a high COD(tot) concentration of 1189 mg/L, with a large
      fraction of COD(sus), viz. 54%. The achieved removal efficiencies in R1 and R2
      for COD(tot), COD(sus), BOD5 and TSS were "56%, 87%, 59% and 81%" and "58%, 90%,
      60% and 82%" for both systems, respectively. R2 achieved a marginal but
      significant (p<0.05) better removal efficiencies of those parameters as compared
      to R1. The COD(col) and COD(dis) removals in R1 and R2 were respectively 31% and
      20%, and 34% and 22%. The sludge accumulation was very low suggesting that the
      desludging frequency will be of several years. Accordingly, the reactor can be
      adequately designed at 2 days HRT.

PMID- 18321700
TI  - Hydrothermal production and characterization of protein and amino acids from silk
      waste.
AB  - Non-catalytic hydrothermal decomposition of sericin and fibroin from silk waste
      into useful protein and amino acids was examined in a closed batch reactor at
      various temperatures, reaction times, and silk to water ratios to examine their
      effects on protein and amino acid yields. For the decomposition of sericin, the
      highest protein yield was found to be 0.466 mg protein/mg raw silk, obtained
      after 10 min hydrothermal reaction of silk waste at 1:100 silk to water ratio at
      120 degrees C. The highest amino acid yield was found to be 0.203 mg amino
      acids/mg raw silk, obtained after 60 min of hydrothermal reaction of silk waste
      at 1:20 silk to water ratio at 160 degrees C. For the hydrothermal decomposition
      of fibroin, the highest protein yield was 0.455 mg protein/mg silk fibroin
      (1:100, 220 degrees C, 10 min) and that of amino acids was 0.755 mg amino
      acids/mg silk fibroin (1:50, 220 degrees C, 60 min). The rate of silk fibroin
      decomposition could be described by surface reaction kinetics. The soluble
      reaction products were freeze-dried to obtain sericin and fibroin particles,
      whose conformation and crystal structure of the particles were shown to differ
      from the original silk materials, particularly in the case of fibroin, in which
      the change from beta-sheet conformation to alpha-helix/random coil was observed.

PMID- 18321701
TI  - Fluorination of triptolide and its analogues and their cytotoxicity.
AB  - The reaction of triptolide and its analogues with a fluorinating agent, that is,
      bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) or (diethylamino)sulfur
      trifluoride (DAST), was studied. One of the fluorinated products, 14beta
      dehydroxy-14beta-fluoro triptolide, was found to be more cytotoxic than the
      parent natural triptolide.

PMID- 18321702
TI  - Glycosyl and polyalcoholic prodrugs of lonidamine.
AB  - Polyhydric alcohol derivatives of the anticancer agent lonidamine (LND) have been
      synthesized. The increased water solubility showed by prodrugs 4, 7, and 25
      together with their logP values (2.19, 2.55, and 2.54, respectively) and chemical
      stability might be beneficial for prodrugs absorption after oral administration.
      Moreover, the new prodrugs undergo enzymatic hydrolysis in plasma and release LND
      demonstrating that they are promising candidates for in vivo investigations.

PMID- 18321703
TI  - New nordihydroguaiaretic acid derivatives as anti-HIV agents.
AB  - Reaction of nordihydroguaiaretic acid with various alkyl chloride, 1
      piperidinecarbonyl chloride, methyl chloroformate, or 1,1'-carbonyldiimidazole
      under alkaline conditions produced the corresponding phenol ethers, carbamates
      and carbonates, respectively, in 67-83% yields. Among these derivatives, the
      nitrogen-containing compounds were converted to the corresponding hydrochloride
      salts. Having good solubility, these NDGA derivatives were found stable in
      aqueous solution. These new compounds exerted appealing activity against HIV Tat
      regulated transactivation in human epithelial cells. The most potent compound
      meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperdino)ethoxyphenyl])butane
      tetrakishydrochloride salt (5b) showed IC(50) value of 0.88 microM.

PMID- 18321704
TI  - Synthesis and evaluation of 3- and 7-substituted geranylgeranyl pyrophosphate
      analogs.
AB  - Protein prenyl transferases have been a focus of anti-cancer drug discovery in
      recent years due to their roles in post-translational modification of small GTP
      binding proteins. Attention is now turning to the development of GGTase I
      inhibitors. Here, we present the synthesis and biological evaluation of four GGPP
      analogs versus mammalian GGTase I and the discovery that 7-allyl GGPP is a
      surprisingly efficient GGTase I substrate.

PMID- 18321705
TI  - Design, synthesis and antiproliferative properties of oligomers with chromophore
      units linked by amide backbones.
AB  - The preparation of oligomers made up of several chromophore units as compounds
      with potential fluorescent and antiproliferative properties is described.
      Specifically, chromophore units with protected-amino groups and one carboxylic
      group are described, together with methods to assemble these units using peptide
      chemistry. Some of these compounds have antiproliferative activity.

PMID- 18321706
TI  - The reliability of physical performance measures in peripheral neuropathy.
AB  - The purpose of this study was to evaluate the test-retest reliability of select
      physical performance measures among people with peripheral neuropathy (PN).
      METHODS: 20 PN patients (12 women, 8 men, mean age=68.4+/-12.5 years) were
      assessed on two separate occasions. Plantar pressure sensitivity was determined
      with a monofilament of known strength. Functional capacity and mobility were
      measured by the 6-min walk (6MW) and timed up-and-go (TUG) tests, respectively.
      Standing balance was evaluated by computing the average velocity (VEL) and area
      enclosing 95% of the body COP (A95) while participants stood quietly with eyes
      closed for multiple trials of varying length. Isokinetic knee extensor and flexor
      peak torque (KEPT, KFPT) were measured with an dynamometer during five maximal
      voluntary contractions. RESULTS: Plantar sensitivity and all measures of physical
      function demonstrated significant reliability. High reliability was observed for
      the 6MW (ICC=0.94) and the two-trial average TUG (ICC=0.99). Similarly, KEPT and
      KFPT were highly reliable whether using the top trial, or averaging the three
      best trials (ICCs>0.96). Averaging multiple standing balance trials generally
      increased ICC values, with 30s trials appearing to possess the highest
      reliability. DISCUSSION: Despite the heterogeneity of the PN population, select
      measures of physical performance are highly reliable and therefore recommended
      for use when examining physical function in these patients.

PMID- 18321707
TI  - Test-retest reliability of spatial and temporal gait parameters of people with
      Alzheimer's disease.
AB  - The reliability of measures of walking in people with Alzheimer's disease (AD)
      has not been established despite the increased variability of their walking
      compared to control groups. The purpose of this study was to examine the test
      retest reliability of temporal and spatial gait measurements in community
      dwelling people with AD. Ten males and 10 females with AD completed 10 walks on
      an instrumented walkway at self-selected comfortable speed on two occasions, 1
      week apart. Data from 10 walks for each subject for each session were averaged
      and test-retest reliability of velocity, cadence, step length, stride length,
      step width, toe in/out angle, swing and stance times was measured using
      intraclass correlation coefficients (ICCs) of the type (3, 1). Coefficients of
      variation (CV) of method error were calculated to determine between-trial
      variability and the minimum detectable change (MDC) was calculated to indicate
      the difference in scores required to show a true change. This analysis was
      repeated for averages of the first three walks for each subject at each session.
      ICCs were found to be high (>0.86) for all gait parameters using both 10 and
      three walks, indicating high test-retest reliability for these measures in people
      with AD with as few as three walks. Measures of support base and toe in/out
      angle, however, had higher CV, even with increased numbers of walks, suggesting
      that only large changes in these parameters can be detected. MDC values suggested
      that demonstration of real change in gait measures is feasible in this
      population.

PMID- 18321708
TI  - Versatile microbial surface-display for environmental remediation and biofuels
      production.
AB  - Surface display is a powerful technique that uses natural microbial functional
      components to express proteins or peptides on the cell exterior. Since the
      reporting of the first surface-display system in the mid-1980s, a variety of new
      systems have been reported for yeast, Gram-positive and Gram-negative bacteria.
      Non-conventional display methods are emerging, eliminating the generation of
      genetically modified microorganisms. Cells with surface display are used as
      biocatalysts, biosorbents and biostimulants. Microbial cell-surface display has
      proven to be extremely important for numerous applications, ranging from
      combinatorial library screening and protein engineering to bioremediation and
      biofuels production.

PMID- 18321709
TI  - Fractures of the tibial spine: epidemiology and outcome.
AB  - We documented functional outcome in 83 knees with tibial spine fractures. The
      mean age at injury was 35 years. There was a medial collateral ligament sprain in
      17 knees and posterolateral corner injury in three knees. Twenty patients with
      displaced tibial spine fractures were treated with fixation of the tibial spine
      and 63 patients with undisplaced or minimally displaced fractures were treated
      non-operatively. Fourteen (22%) non-operatively treated knees developed
      symptomatic instability, three of which underwent ACL reconstruction. Tibial
      spine fixation restored stability in 18 of 20 knees, but knee stiffness was more
      common in this group when compared to non-operatively treated knees (60% vs 19%,
      p<0.0005). Patients with postoperative knee stiffness had a mean age of 28 years
      compared to 18 in patients with no knee stiffness (p<0.05). We concluded that
      tibial spine fracture in skeletally mature patients is associated with a
      significant risk of knee stiffness and instability.

PMID- 18321711
TI  - Synthesis and in vitro anti-leishmanial activity of 1-[5-(5-nitrofuran-2-yl)
      1,3,4-thiadiazol-2-yl]- and 1-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl]-4
      aroylpiperazines.
AB  - The synthesis and anti-leishmanial activity of nitroheteroaryl-1,3,4-thiadiazole
      based compounds including 1-[5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-yl]-4
      aroylpiperazines and 1-[5-(5-nitrothiophen-2-yl)-1,3,4-thiadiazol-2-yl]-4
      aroylpiperazines were described. Most of the synthesized compounds exhibited
      potent anti-leishmanial activity against both promastigote and amastigote forms
      of Leishmania major at non-cytotoxic concentrations. In general, 5-nitrofuran
      derivatives were more active than the corresponding 5-nitrothiophene analogues.

PMID- 18321710
TI  - Synthesis and structure-activity relationship studies on tryprostatin A, an
      inhibitor of breast cancer resistance protein.
AB  - Tryprostatin A is an inhibitor of breast cancer resistance protein, consequently
      a series of structure-activity studies on the cell cycle inhibitory effects of
      tryprostatin A analogues as potential antitumor antimitotic agents have been
      carried out. These analogues were assayed for their growth inhibition properties
      and their ability to perturb the cell cycle in tsFT210 cells. SAR studies
      resulted in the identification of the essential structural features required for
      cytotoxic activity. The absolute configuration L-Tyr-L-pro in the
      diketopiperazine ring along with the presence of the 6-methoxy substituent on the
      indole moiety of 1 was shown to be essential for dual inhibition of topoisomerase
      II and tubulin polymerization. Biological evaluation also indicated the presence
      of the 2-isoprenyl moiety on the indole scaffold of 1 was essential for potent
      inhibition of cell proliferation. Substitution of the indole N(a)-H in 1 with
      various alkyl or aryl groups, incorporation of various L-amino acids into the
      diketopiperazine ring in place of L-proline, and substitution of the 6-methoxy
      group in 1 with other functionality provided active analogues. The nature of the
      substituents present on the indole N(a)-H or the indole C-2 position influenced
      the mechanism of action of these analogues. Analogues 68 (IC(50)=10 microM) and
      67 (IC(50)=19 microM) were 7-fold and 3.5-fold more potent, respectively, than 1
      (IC(50)=68 microM) in the inhibition of the growth of tsFT210 cells. Diastereomer
      2 of tryprostatin B 8 was a potent inhibitor of the growth of three human
      carcinoma cell lines: H520 (IC(50)=11.9 microM), MCF-7 (IC(50)=17.0 microM) and
      PC-3 (IC(50)=11.1 microM) and was equipotent with etoposide, a clinically used
      anticancer agent. Isothiocyanate analogue 71 and 6-azido analogue 72 were as
      potent as 1 in the tsFT210 cell proliferation and may be useful tools in labeling
      BCRP.

PMID- 18321712
TI  - Identification of novel ligands for the RNA pseudoknot that regulate -1 ribosomal
      frameshifting.
AB  - In many viruses, -1 ribosomal frameshifting (-1RF) regulates synthesis of
      proteins and is crucial for virus production. An RNA pseudoknot is one of the
      essential components of the viral -1RF system. Thermodynamic or kinetic control
      of pseudoknot folding may be important in regulating the efficiency of -1RF.
      Thus, small molecules that interact with viral RNA pseudoknots may disrupt the 
      1RF system and show antiviral activity. In this study, we conducted virtual
      screening of a chemical database targeting the X-ray crystal structure of RNA
      pseudoknot complexed with biotin to identify ligands that may regulate an -1RF
      system containing biotin-aptamer as an RNA pseudoknot component. After docking
      screening of about 80,000 compounds, 58 high-ranked hits were selected and their
      activities were examined by in vitro and cell-based -1 frameshifting assays. Six
      compounds increased the efficiency of -1 frameshifting, and these are novel small
      molecule compounds that regulate the -1RF.

PMID- 18321713
TI  - Synthesis, checkpoint kinase 1 inhibitory properties and in vitro
      antiproliferative activities of new pyrrolocarbazoles.
AB  - In the course of structure-activity relationship studies on granulatimide
      analogues, new pyrrolo[3,4-c]carbazoles have been synthesized in which the
      imidazole heterocycle was replaced by a five-membered ring lactam system or a
      dimethylcyclopentanedione. Moreover, the synthesis of an original structure in
      which a sugar moiety is attached to the indole nitrogen and to a six-membered D
      ring via an oxygen is reported. The inhibitory activities of the newly
      synthesized compounds toward checkpoint kinase 1 and their in vitro
      antiproliferative activities toward three tumor cell lines: murine leukemia
      L1210, and human colon carcinoma HT29 and HCT116 are described.

PMID- 18321714
TI  - Antifungal and antimycobacterial activity of 1-(3,5-diaryl-4,5-dihydro-1H-pyrazol
      4-yl)-1H-imidazole derivatives.
AB  - 1-(3,5-Diaryl-4,5-dihydro-1H-pyrazol-4-yl)-1H-imidazole derivatives were
      synthesized and tested for their in vitro antifungal and antimycobacterial
      activities. These imidazole derivatives showed an excellent antifungal activity
      against a clinical strain of Candida albicans and an interesting antitubercular
      activity against Mycobacterium tuberculosis H(37)Rv reference strain.

PMID- 18321715
TI  - Synthesis of 1-/2-substituted-[1,2,3]triazolo[4,5-g]phthalazine-4,9-diones and
      evaluation of their cytotoxicity and topoisomerase II inhibition.
AB  - Studies on antitumor heterocyclic quinones containing nitrogens revealed that the
      number and position of nitrogens on the heterocyclic ring have significance on
      cytotoxicity of quinones. In our continuous effort to find more cytotoxic quinone
      compounds, we designed triazolophthalazine analogues in order to introduce more
      nitrogens on the heterocyclic quinones. 1-/2-Substituted-[1,2,3]triazolo[4,5
      g]phthalazine-4,9-diones were synthesized by 1,3-dipolar addition of phthalazine
      5,8-dione and 4-methoxybenzyl azide by modification of previously reported
      method. The cytotoxicity of the synthesized compounds was evaluated by a SRB
      (sulforhodamine B) assay against nine types of human cancer cell lines and
      inhibition against topoisomerase II (Topo II) of them was assessed by a
      decatenation assay. Most of the synthesized compounds showed considerably higher
      cytotoxicity than that of doxorubicin. Also, topoisomerase II inhibitory activity
      of the tested compounds was higher than that of etoposide and IC(50) values of
      the compounds were 19.4-64.5 microM.

PMID- 18321716
TI  - ATP competitive inhibitors of D-alanine-D-alanine ligase based on protein kinase
      inhibitor scaffolds.
AB  - D-Alanine-D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall
      biosynthesis and an important target for developing new antibiotics. Here, we
      describe a new approach to identify new inhibitor scaffolds for DDl based on
      similarity in the ATP binding region of different kinases and DDl. After an
      initial screening of several protein kinase inhibitors, we found that the
      Brutons's tyrosine kinase inhibitor LFM-A13, an analog of the Leflunomide
      metabolite A771726, inhibits DDl with a K(i) of 185 microM. A series of
      malononitrilamide and salicylamide derivatives of LFM-A13 has been synthesized to
      confirm the validity of this scaffold as an inhibitor of DDl.

PMID- 18321717
TI  - 1-(2-Carboxyindol-5-yloxy)propan-2-ones as inhibitors of human cytosolic
      phospholipase A2alpha: synthesis, biological activity, metabolic stability, and
      solubility.
AB  - Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 were
      previously reported to be potent inhibitors of cytosolic phospholipase A(2)alpha
      (cPLA(2)alpha) isolated from human platelets. In continuation of our attempts to
      develop novel cPLA(2)alpha inhibitors, a series of structurally related indole-2
      carboxylic acids containing 3-aryloxy-2-oxopropoxy residues in position 5 were
      synthesized and tested for their cPLA(2)alpha-inhibitory potency. Furthermore,
      the thermodynamic solubility of these compounds and their metabolic stability
      against rat liver microsomes were evaluated.

PMID- 18321718
TI  - Synthesis and antibacterial activity of egonol derivatives.
AB  - Synthesis of egonol derivatives, 5-(3''-chloropropyl)-7-methoxy-2-(3',4'
      methylenedioxyphenyl)benzofuran 1, 5-(3''-bromopropyl)-7-methoxy-2-(3',4'
      methylenedioxyphenyl)benzofuran 2, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1
      benzofuran-5-yl]propanal 3, 5-(3''-iodopropyl)-7-methoxy-2-(3',4'
      methylenedioxyphenyl)benzofuran 4, 5-[3-(3''-bromopropyloxy) propyl]-7-methoxy-2
      (3',4'-methylenedioxyphenyl)benzofuran 5, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1
      benzofuran-5-yl]propylmethanoate 6, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1
      benzofuran-5-yl]propyloleate 7, 5-[3''-hydroxypropyl]-6-bromo-7-methoxy-2-(3',4'
      methylenedioxyphenyl)benzofuran 8, 4-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1
      benzofuran-5-yl]butanenitrile 9, 3-[2-(1,3-benzodioxol-5-yl)-7-methoxy-1
      benzofuran-5-yl]propylbenzoate 10, 5-[3''-hydroxypropyl]-7-methoxy-3-nitro-2
      (3',4'-methylenedioxyphenyl)benzofuran 11 and their antibacterial activity
      against Staphylococcus aureus, Bacillus subtilis, Candida albicans and
      Escherichia coli are reported. The starting material egonol 5-[3''
      (hydroxy)propyl]-7-methoxy-2-(3', 4'methylenedioxyphenyl)benzofuran was isolated
      from seeds of Styrax officinalis L. The structural elucidication of these
      compounds (1-11) was established using 1D ((1)H, (13)C), 2D NMR (HMBC, HMQC,
      COSY) and LCMS spectroscopic data. While egonol and some synthesised new
      compounds show similar antibacterial activity and MIC values against S. aureus,
      B. subtilis, C. albicans and E. coli, other new derivatives show different
      activity against S. aureus, B. subtilis, C. albicans and E. coli.

PMID- 18321719
TI  - Characterisation of phases in nanostructured, multilayered titanium alloys by
      analytical and high-resolution electron microscopy.
AB  - Surface processing of a Ti-6Al-4V alloy led to a complex multilayered
      microstructure containing several phases of the Ni-Ti-P-Al-O system, which
      improves the mechanical and tribological surface properties. The microstructure,
      chemical and phase compositions of the hard layer formed on the surface were
      investigated by LM, XRD, SEM as well as analytical/high-resolution TEM, STEM,
      EDS, electron diffraction and FIB. Phase identification based on electron
      diffraction, HRTEM and EDS microanalysis revealed the presence of several binary
      and ternary phases in the system Ti-Ni-P, sometimes with partial substitution of
      Ti by Al. However some phases, mainly nanoparticles, still remain not identified
      satisfactorily. Electron microscopy techniques used for identification of phases
      present in surface multilayers and some practical limits to their routine
      application are reminded here.

PMID- 18321720
TI  - Separation of image-distortion sources and magnetic-field measurement in scanning
      electron microscope (SEM).
AB  - The electron-microscope image distortion generated by electromagnetic
      interference (EMI) is an important problem for accurate imaging in scanning
      electron microscopy (SEM). Available commercial solutions to this problem utilize
      sophisticated hardware for EMI detection and compensation. Their efficiency
      depends on the complexity of distortions influence on SEM system. Selection of a
      proper method for reduction of the distortions is crucial. The current
      investigations allowed for a separation of the distortions impact on several
      components of SEM system. A sum of signals from distortion sources causes wavy
      deformations of specimen shapes in SEM images. The separation of various reasons
      of the distortion is based on measurements of the periodic deformations of the
      images for different electron beam energies and working distances between the
      microscope final aperture and the specimen. Using the SEM images, a direct
      influence of alternating magnetic field on the electron beam was distinguished.
      Distortions of electric signals in the scanning block of SEM were also separated.
      The presented method separates the direct magnetic field influence on the
      electron beam below the SEM final aperture (in the chamber) from its influence
      above this aperture (in the electron column). It also allows for the measurement
      of magnetic field present inside the SEM chamber. The current investigations gave
      practical guidelines for selecting the most efficient solution for reduction of
      the distortions.

PMID- 18321721
TI  - Cs diffusion in local Taiwan laterite with different solution concentration, pH
      and packing density.
AB  - In this work we used an "in-diffusion" method to study the effects of pH,
      solution concentration and packing density on Cs diffusion by packing local
      Taiwan laterite (LTL) into modified capillary columns with 5mm diameter. These
      packed columns were first pre-equilibrated with synthetic groundwater (GW) for 3
      weeks. The diffusion experiments were then carried out at ambient condition for 2
      weeks. Our experimental results showed that the Cs diffusion profile fits Fick's
      second law very well in given experimental conditions, indicating the validity of
      modified capillary column method. Generally speaking, Cs diffusion in LTL
      decreases as the pH increases and as Cs concentration decreases. The apparent
      diffusion coefficient (D(a)) increases from 5.52 x 10(-12) (10(-7)M) to 2.18 x
      10(-11) (10(-3)M)m(2)/s, while the effective diffusion coefficient (D(e)) shows
      slight variation as the Cs concentration changes. Both the derived D(a) and D(e)
      values decrease as the pH increases, implying that the diffusion mechanisms of Cs
      nuclide in alkaline and acid environment are different. In addition, our results
      show that Cs diffusion is unaffected by the given packing density, indicating the
      interlaminary space is not the major determinant of Cs adsorption and diffusion
      in LTL.

PMID- 18321722
TI  - The structure and function of plant hemoglobins.
AB  - Plants, like humans, contain hemoglobin. Three distinct types of hemoglobin exist
      in plants: symbiotic, non-symbiotic, and truncated hemoglobins. Crystal
      structures and other structural and biophysical techniques have revealed
      important knowledge about ligand binding and conformational stabilization in all
      three types. In symbiotic hemoglobins (leghemoglobins), ligand binding regulatory
      mechanisms have been shown to differ dramatically from myoglobin and red blood
      cell hemoglobin. In the non-symbiotic hemoglobins found in all plants, crystal
      structures and vibrational spectroscopy have revealed the nature of the
      structural transition between the hexacoordinate and ligand-bound states. In
      truncated hemoglobins, the abbreviated globin is porous, providing tunnels that
      may assist in ligand binding, and the bound ligand is stabilized by more than one
      distal pocket residue. Research has implicated these plant hemoglobins in a
      number of possible functions differing among hemoglobin types, and possibly
      between plant species.

PMID- 18321723
TI  - Clinical implementation of a multidirectional, angular stable osteosynthesis
      system in maxillofacial traumatology.
AB  - AIM: To investigate whether a multidirectional, angular stable osteosynthesis
      system is suitable for the treatment of mandibular fractures and to compare it
      with well established available systems. MATERIAL AND METHODS: Following
      preliminary testing in an animal model, the multidirectional angular stable
      system TiFix 2.3 obtained from Litos (Hamburg, Germany) was utilised for internal
      fixation of 39 mandibular fractures. These involved four symphyseal fractures, 17
      parasymphyseal, 16 of the angle of the mandible and two comminuted fractures. The
      surgical and postoperative course was closely scrutinised. Radiographs were taken
      after 6 months and all plates removed under local anaesthesia. Photographs were
      taken intraoperatively and the plates and surrounding soft tissues were salvaged
      for histological analysis. Additionally, these operations were compared with
      treatment of equivalent fractures which were treated with conventional, non
      angular stable systems. The relative costs have also been evaluated. RESULTS: In
      33 of the 39 fractures one TiFix plate sufficed for osteosynthesis. The plate
      most often used was a 2-hole plate which was applied in 25 (55.5%) fractures,
      followed by the 4-hole plates used in 16 (35.5%) fractures. In two comminuted
      fractures, four 6-hole plates were used (9%). In 17 patients the operation lasted
      less than 30 min, in 20 patients less than 60 min, in two less than 120 min. In
      all cases, the operations were shorter, and due to the plates' dimensions fewer
      screws had to be used, thus reducing the costs. DISCUSSION: This angular stable
      system enabled reduction of the amount of the implant material. Also reduced were
      the operation time and the cost of the procedure. Furthermore, in the future it
      will allow smaller access incisions and better preservation of the soft tissue
      integrity.

PMID- 18321724
TI  - Influence of summer daylight saving time on scattered erythemal solar ultraviolet
      exposures.
AB  - The research question of whether there are any influences in the scattered or
      diffuse erythemal UV exposures to a horizontal plane over a five month period due
      to the change from standard time to daylight saving time, has been investigated
      by using physical measurements and applying them to both standard time and
      daylight saving time. The diffuse erythemal UV was considered for fixed lunch
      break times and fixed morning and afternoon break times. The cases considered
      were for groups of the population who are predominantly indoors and who spend
      their break times outdoors in shade. The biggest influence on the diffuse UV
      exposures of changing to daylight saving time is the timing of the outdoor meal
      and break times. The change causes a reduction in diffuse erythemal exposure for
      early or morning breaks and an increase in the diffuse erythemal exposure for
      late or afternoon breaks. Similarly, for the lunch break times, the changes in
      exposure are influenced by the timing of the break with respect to solar noon.
      Indoor workers who take their breaks outside in a shaded area may have a change
      in their exposure to diffuse UV due to a shift to daylight saving time, however
      the magnitude of this change and whether it is a positive or negative change in
      exposure will depend on the timing of the break. The increase in diffuse UV
      exposure due to the afternoon break may be negated by the decrease in exposure
      due to the morning break. In this case, the effect on diffuse UV exposures due to
      changing to daylight saving time will be minimal.

PMID- 18321725
TI  - Inhibitory effect of activin A on activation of lipopolysaccharide-stimulated
      mouse macrophage RAW264.7 cells.
AB  - Activin A is a member of transforming growth factor beta (TGF-beta) superfamily,
      which is also named restrictin-P, and can inhibit the secretion of nitric oxide
      (NO) and interleukin-1beta (IL-1beta) from LPS-activated mouse macrophages. In
      this study, the regulation effect and possible mechanism of activin A as an anti
      inflammatory factor on lipopolysaccharide (LPS)-activated macrophages were
      investigated in vitro. It was observed that activin A could not only decrease the
      secretion of IL-1beta and NO, as well as the mRNA expressions of IL-1beta and
      iNOS, but also suppress the pinocytosis of mouse macrophage cell line RAW264.7
      cells induced by LPS. In addition, activin A could obviously reduce the
      expressions of CD68 and CD14, as well as Toll-like receptor 4 (TLR4) on RAW264.7
      cells induced by LPS, but could not influence the proliferation of RAW264.7
      cells. These findings suggest that activin A may play an important down
      regulation role in inflammatory factor production and phagocytosis of the
      activated macrophages via suppressing the maturation of LPS-induced macrophages
      or LPS-TLR4 signal transduction.

PMID- 18321726
TI  - New role of IKK alpha/beta phosphorylated I kappa B alpha in axon outgrowth and
      axon initial segment development.
AB  - Neuronal polarity development begins by the outgrowth of the axon and the
      formation of the axon initial segment which acts as a diffusion barrier and it is
      the place of action potential generation. The mechanisms controlling this
      development are largely unknown. We describe a role for IkappaB alpha, the
      NFkappaB inhibitor, in the initial stages of axon outgrowth and the development
      of the axon initial segment. In cultured hippocampal neurons, inhibition of
      IkappaB alpha phosphorylation by IkappaB kinases (IKKs) impedes axon outgrowth.
      Moreover, the absence of IkappaB alpha phosphorylation, in the next stages of
      axon development, impairs the localization of structural and functional proteins
      at the axon initial segment, such as ankyrin G and voltage gated sodium channels.
      These results demonstrate a new role for proteins of the NFkappaB pathway in the
      acquisition of neuronal polarity and its involvement in the development of the
      axon initial segment.

PMID- 18321727
TI  - Conformational changes accompany activation of reovirus RNA-dependent RNA
      transcription.
AB  - Many critical biologic processes involve dynamic interactions between proteins
      and nucleic acids. Such dynamic processes are often difficult to delineate by
      conventional static methods. For example, while a variety of nucleic acid
      polymerase structures have been determined at atomic resolution, the details of
      how some multi-protein transcriptase complexes actively produce mRNA, as well as
      conformational changes associated with activation of such complexes, remain
      poorly understood. The mammalian reovirus innermost capsid (core) manifests all
      enzymatic activities necessary to produce mRNA from each of the 10 encased double
      stranded RNA genes. We used rapid freezing and electron cryo-microscopy to trap
      and visualize transcriptionally active reovirus core particles and compared them
      to inactive core images. Rod-like density centered within actively transcribing
      core spike channels was attributed to exiting nascent mRNA. Comparative radial
      density plots of active and inactive core particles identified several structural
      changes in both internal and external regions of the icosahedral core capsid.
      Inactive and transcriptionally active cores were partially digested with trypsin
      and identities of initial tryptic peptides determined by mass spectrometry.
      Differentially-digested peptides, which also suggest transcription-associated
      conformational changes, were placed within the known three-dimensional structures
      of major core proteins.

PMID- 18321728
TI  - A Toll receptor from Chinese shrimp Fenneropenaeus chinensis is responsive to
      Vibrio anguillarum infection.
AB  - Toll-like receptors (TLRs) are an evolutionarily ancient family of pattern
      recognition receptors (PRRs), playing a crucial role in innate immune responses.
      Here we present a Toll homolog from Chinese shrimp Fenneropenaeus chinensis,
      designated FcToll. The full-length cDNA of FcToll is 4115 bp including a poly A
      tail of 16 bp, encoding a putative protein of 931 amino acids. The predicted
      protein consists of an extracellular domain with a potential signal peptide, 16
      leucine-rich repeats (LRR), two LRR-C-terminal (LRR-CT) motifs, and two LRR-N
      terminal (LRR-NT) motifs, followed by a transmembrane segment of 23 amino acids,
      and a cytoplasmic Toll/Interleukin-1R (TIR) domain of 139 residues. Genomic
      structure of FcToll gene contains five exons and four introns. Phylogenetic
      analysis revealed that it belongs to insect-type invertebrate Toll family.
      Transcripts of FcToll gene were constitutively expressed in various tissues, with
      predominant level in lymphoid organ. Real-time PCR assays demonstrated that
      expression patterns of FcToll were distinctly modulated after bacterial or viral
      stimulation, with significant enhancement after 5h post-Vibrio anguillarum
      challenge but markedly reduced levels immediately after white spot syndrome virus
      (WSSV) exposure. These results suggest that FcToll might be involved in innate
      host defense, especially against the pathogen V. anguillarum.

PMID- 18321729
TI  - Genomic organisation of the channel catfish Mx1 gene and characterisation of
      multiple channel catfish Mx gene promoters.
AB  - In order to further characterise channel catfish (Ictalurus punctatus) Mx1,
      studies were initiated to amplify and clone the Mx1 promoter into a reporter
      vector, pGL3basic. Initially the Mx1 gene was amplified from genomic DNA and was
      found to have 12 exons and 11 introns, spanning a region over 6 kilobases (kb) in
      length. The Mx1 promoter was amplified using genome walking and during this
      process four additional Mx promoters were identified, suggesting the presence of
      five Mx genes in the channel catfish. All five promoters possess an interferon
      stimulated response element (ISRE) and the Mx1 promoter possessed two potential
      NF-kappabeta transcription sites. Following cloning each construct was
      transiently transfected into COS-7 and EPC cells for 24h and treated with 5
      microg/ml poly I:C for 24h. An increase in expression of the reporter gene in
      response to poly I:C was noted in both cell lines in the pGL3Mx1 construct only.
      However, the reporter gene was also constitutively expressed in these cells.
      Constitutive expression was also observed in channel catfish ovary cells
      transiently transfected with pGL3Mx1 only. Treatment with 5 microg/ml poly I:C
      did not increase this expression, which may be due to high levels of cell death
      in this difficult to transfect cell line. The constitutive expression observed
      implies that a repressor element is missing in the 390 base pair sequence of the
      Mx1 promoter used in this study. These results suggest that only channel catfish
      Mx1 is involved in the type I interferon pathway and that the presence of an ISRE
      in a regulatory region is not necessarily indicative of a role in the type I
      interferon response.

PMID- 18321730
TI  - Myelin water imaging of multiple sclerosis at 7 T: correlations with
      histopathology.
AB  - Myelin water imaging (MWI) promises to be invaluable in understanding
      neurological diseases like MS. However, a limitation of MWI is signal to noise
      ratio. Recently, a number of investigators have performed MWI at field strengths
      higher than 1.5 T. Our goal was to determine if myelin water imaging at increased
      SNR, arising from the use of a small bore 7 T MR system with optimized coil
      geometry, enables the production of superior myelin water maps with increased
      spatial detail and enables better correlations with histology. Ten formalin-fixed
      MS brain samples underwent a 32-echo T(2) relaxation experiment which measured
      myelin water fraction (MWF) on a 7-T animal MRI scanner. MWF correlated strongly
      qualitatively and quantitatively with luxol fast blue staining for myelin [mean
      (range): R(2)=0.78 (0.56-0.95), p<0.0001]. The quality and detail of 7 T myelin
      water maps were far superior to that previously seen at 1.5 T, allowing for
      visualization of fine structures such as the normal prominent myelination of the
      deeper cortical layers, the alveus of the hippocampus and rings of preserved
      myelin in a concentric Balo's lesion. 7 T imaging will allow detailed assessment
      of myelin pathology to a degree not possible with lower field strengths.

PMID- 18321731
TI  - The cortical energy needed for conscious perception.
AB  - The brain's information processing power is limited by its energy supply but the
      allocation of cortical energy use between conscious and unconscious information
      processing is unknown. We calculate, from electrophysiological data in primates,
      that conscious perception reflects surprisingly small local alterations in mean
      cortical neuronal firing rate and energy consumption: perceiving visual stimulus
      movement, altered tactile vibration frequency, or tone stream separation, changes
      local cortical energy use by less than 6%. Our estimations of energy use suggest
      that a "design strategy", of encoding signals using separate neurons that
      increase and decrease their firing rate, serves to minimise changes of energy use
      in the cortical areas mediating perception and may result in stimulus perception
      failing to be detected by BOLD functional imaging.

PMID- 18321732
TI  - A complete species-level molecular phylogeny for the "Eurasian" starlings
      (Sturnidae: Sturnus, Acridotheres, and allies): recent diversification in a
      highly social and dispersive avian group.
AB  - We generated the first complete phylogeny of extant taxa in a well-defined clade
      of 26 starling species that is collectively distributed across Eurasia, and which
      has one species endemic to sub-Saharan Africa. Two species in this group-the
      European starling Sturnus vulgaris and the common Myna Acridotheres tristis-now
      occur on continents and islands around the world following human-mediated
      introductions, and the entire clade is generally notable for being highly social
      and dispersive, as most of its species breed colonially or move in large flocks
      as they track ephemeral insect or plant resources, and for associating with
      humans in urban or agricultural landscapes. Our reconstructions were based on
      substantial mtDNA (4 kb) and nuclear intron (4 loci, 3 kb total) sequences from
      16 species, augmented by mtDNA NDII gene sequences (1 kb) for the remaining 10
      taxa for which DNAs were available only from museum skin samples. The resulting
      mitochondrial gene tree embedded within a multilocus framework shows that the
      well-studied taxa S. vulgaris/unicolor are the sister lineage to the remaining
      members of the radiation, from which other relatively early lineages gave rise to
      forms that are now nomadic or locally migrant in Africa (Creatophora) and western
      Asia (Pastor). The remaining taxa form a clade with a complicated biogeographic
      history primarily in central and eastern Asia; this group contains a range of
      sedentary to highly migratory taxa, as well as widely distributed species and
      single-island endemics such as the highly endangered Bali myna (Leucopsar).
      Several groups of species in the genus Acridotheres have low magnitudes of within
      group divergence and likely diversified via their respective colonization of
      islands. The taxonomy of this entire group has remained highly volatile over the
      past century; we propose dividing these 26 species among 11 reciprocally
      monophyletic genera (Acridotheres, Poliopsar, Temenuchus, Sturnornis, Leucopsar,
      Gracupica, Agropsar, Pastor, Creatophora, and Sturnus).

PMID- 18321733
TI  - A hypercalcified sponge with soft relatives: Vaceletia is a keratose demosponge.

PMID- 18321734
TI  - Myoclonic absence epilepsy with photosensitivity and a gain of function mutation
      in glutamate dehydrogenase.
AB  - Activating mutations in glutamate dehydrogenase (GDH), de novo or dominantly
      inherited, are responsible for the hyperinsulinism/hyperammonemia (HI/HA)
      syndrome. Epilepsy has been frequently reported in association with mutations in
      GDH, but the epilepsy phenotype has not been clearly determined. Here, we
      describe a family with a dominantly inherited mutation in GDH. The mother,
      brother and both sisters had myoclonic absence seizures, but only the mother and
      one sister had the complete HI/HA pattern. For the two sisters with myoclonic
      absences, epilepsy started during the second year of life while the brother, it
      started at 6 years. All 3 children showed the same EEG pattern characterized by
      photosensitive generalized and irregular spike-wave discharges and runs of
      multiple spikes. The mother's EEG recordings were normal without
      photosensitivity. Magnetic resonance imaging (MRI) and spectroscopy (MRS) were
      normal. A direct effect of the GDH mutation, perhaps in combination with
      recurrent hypoglycemia and chronic hyperammonemia could provide a
      pathophysiological explanation for the epilepsy observed in this syndrome and
      these are discussed.

PMID- 18321735
TI  - Comparison between chondroprotective effects of glucosamine, curcumin, and
      diacerein in IL-1beta-stimulated C-28/I2 chondrocytes.
AB  - OBJECTIVE: To compare the effects of glucosamine (GlcN), curcumin, and diacerein
      in immortalized human C-28/I2 chondrocytes at the cellular and the gene
      expression level. This study aimed to provide insights into the proposed
      beneficial effects of these agents and to assess the applicability of the C-28/I2
      cell line as a model for the evaluation of chondroprotective action. METHODS:
      Interleukin-1beta (IL-1beta)-stimulated C-28/I2 cells were cultured in the
      presence of GlcN, curcumin, and diacerein prior to the evaluation of parameters
      such as viability, morphology and proliferation. The impact of GlcN, curcumin,
      and diacerein on gene expression was determined using quantitative real-time RT
      PCR (qPCR). RESULTS: At the transcriptional level, 5 mM GlcN and 50 microM
      diacerein increased the expression of cartilage-specific genes such as aggrecan
      (AGC) and collagen type II (COL2), while reducing collagen type I (COL1) mRNA
      levels. Moreover, the IL-1beta-mediated shift in gene expression pattern was
      antagonized by GlcN and diacerein. These effects were associated with a
      significant reduction in cellular proliferation and the development of
      chondrocyte-specific cell morphology. In contrast, curcumin was not effective at
      lower concentrations but even damaged the cells at higher amounts. CONCLUSIONS:
      Both GlcN and diacerein promoted a differentiated chondrocytic phenotype of
      immortalized human C-28/I2 chondrocytes by altering proliferation, morphology,
      and COL2/COL1 mRNA ratios. Moreover, both agents antagonized inhibitory effects
      of IL-1beta by enhancing AGC and COL2 as well as by reducing COL1 mRNA levels.

PMID- 18321736
TI  - Iron responses in hepatic, intestinal and macrophage/monocyte cell lines under
      different culture conditions.
AB  - Iron homeostasis is mainly controlled by the liver-produced hepcidin peptide,
      which induces the degradation of the ferroportin iron exporter and thus regulates
      serum iron level. Hepcidin transcription is clearly up-regulated by the pro
      inflammatory cytokine IL-6 and down-regulated, in the case of iron depletion, at
      least via HIF transcription factors. In addition, in vivo iron overload up
      regulates hepcidin, but this cannot be reproduced in cell culture or isolated
      hepatocytes. Here, we investigated the steady state mRNA levels of a series of
      genes involved in iron metabolism in hepatic HepG2, intestinal Caco-2, and
      monocyte/macrophage THP-1 cell lines under different iron and culture conditions.
      Our results showed that iron-saturated transferrin up-regulated hepcidin mRNA
      synthesis from HepG2 via cross-talk with macrophages or enterocyte cytokine
      producing cells, whereas non-transferrin-bound iron down-regulated hepcidin,
      likely due to missing TfR-iron-transferrin uptake.

PMID- 18321737
TI  - Evidence of neuroaxonal degeneration in myofascial pain syndrome: a study of
      neuromuscular jitter by axonal microstimulation.
AB  - The mechanism of myofascial pain syndrome (MPS) is unclear. Previous reports
      pointed out that pathogenesis of either referred pain or local twitch response in
      trigger point of MPS is related to the nerve degeneration and disintegration of
      motor and sensory nerves in spinal cord. The purpose of the present study is to
      investigate the evidence of neuromuscular transmission disorders in trigger point
      muscles of patients with MPS by using stimulated single-fiber electromyography
      (SFEMG) examination. Twenty-three patients with neck MPS and 16 age-matched
      controls attended for the present study. The jitter or mean consecutive
      difference (MCD) was calculated as the mean of the absolute differences for 30
      consecutive interpotential intervals between stimuli and single-fiber potentials
      in trapezius and levator scapulae muscles. The relationship between the MCD
      values and the disease duration was measured. The results showed significantly
      increased MCDs in trapezius and levator scapulae muscles in MPS patients. MCD
      values measured in the trigger point muscles were found to be positively
      correlated with the disease duration. The present study with axonal
      microstimulation and SFEMG demonstrates a prominent evidence of neuroaxonal
      degeneration and neuromuscular transmission disorders in the trigger point
      muscles of MPS patients. The mechanism of MPS is possibly implicated with the
      degeneration of motor neurons.

PMID- 18321738
TI  - Is the interleukin-6 haplotype a prognostic factor for sciatica?
AB  - AIMS: We have shown in a cross-sectional setting that an IL6 haplotype (GGGA) is
      associated with intervertebral disc disease (IDD) characterized by sciatica. The
      aim of this study was to evaluate the prognostic role of the GGGA haplotype in
      IDD. METHODS: DNA from 153 sciatica patients who participated in a randomized
      controlled trial of periradicular infiltration was analysed for IL6 variations
      rs1800797 (-596A>G), rs1800796 (-572G>C), rs1800795 (-174G>C), and rs13306435
      (+15T>A). The patients recorded back and leg pain intensity and duration,
      disability by Oswestry Index and back-related sickness absence over a three-year
      follow-up. Repeated measures and univariate analysis of variance with adjustment
      for age, gender and physical work load were used in statistical analyses for the
      last two-years of the follow-up. RESULTS: The prevalence of the GGGA haplotype
      was 9% (14/153). Subjects with the GGGA haplotype did not differ from those
      without the haplotype with respect to pain intensity, or disability score, but
      days with back and leg pain and days on sick leave were significantly higher
      among subjects with the IL6 haplotype after adjustment for occupation (p=0.006,
      0.001 and 0.002, respectively). An interaction between the IL6 haplotype and
      physical work load was significant for the duration of back and leg pain and sick
      leave (p=0.038, 0.011 and 0.006, respectively). CONCLUSIONS: This is the first
      observation of any prognostic genotype among sciatica patients. The IL6 haplotype
      GGGA predicted the number of days with back or leg pain and also sickness
      absence. Subjects with the IL6 haplotype may be more vulnerable when doing
      physically demanding jobs.

PMID- 18321739
TI  - Upregulation and redistribution of ephrinB and EphB receptor in dorsal root
      ganglion and spinal dorsal horn neurons after peripheral nerve injury and dorsal
      rhizotomy.
AB  - EphrinB-EphB receptor signaling plays diverse roles during development, but
      recently has been implicated in synaptic plasticity in the matured nervous system
      and in pain processes. The present study investigated the correlation between
      expression of ephrinB and EphB receptor proteins and chronic constriction injury
      (CCI) of the sciatic nerve and dorsal rhizotomy (DR) in dorsal root ganglion
      (DRG) and spinal cord (SC); and interaction of CCI and DR on expression of these
      signals. Adult, male Sprague-Dawley rats were employed and thermal sensitivity
      was determined in the sham operated CCI and DR rats. Western blot and
      immunobiochemistry analysis and immunofluorescence staining techniques were used
      to detect the expression and location of the ephrinB-EphB receptor proteins in
      DRG and SC. The results showed that expression of ephrinB1 and EphB1 receptor
      proteins was significantly upregulated in DRG and SC in a time-dependent manner
      corresponding to the development of thermal hyperalgesia after CCI. The increased
      expression is predominately located in the medium- and small-sized DRG neurons,
      the superficial layers of spinal dorsal horn (DH) neurons, and the IB4 positive
      nociceptive terminals. DR increases ephrinB1 in DRG, not SC and EphB receptor in
      SC, not DRG. DR suppressed CCI-induced upregulation of ephrinB1 in SC and EphB1
      receptor in DRG and SC. These findings indicate that ephrinB-EphB receptor
      activation and redistribution in DRG and DH neurons after nerve injury could
      contribute to neuropathic pain. This study may also provide a new mechanism
      underlying DR-induced analgesia in clinic.

PMID- 18321740
TI  - Enhancement of offset analgesia during sequential testing.
AB  - Interruption of a continuous noxious heat by a relatively greater noxious heat
      evokes reductions in pain experience when the original noxious heat returns. The
      reduction is greater than that evoked by continuous delivery of noxious heat.
      This disproportionate reduction in pain experience, known as offset analgesia, is
      presumably mediated by a mechanism different to adaptation or habituation.
      Reduction in pain experience to an equivalent noxious stimulus, however, has also
      been demonstrated when applying the same stimulus over a number of days. This
      reduction due to repeated days of stimulation is known as attenuation. In order
      to distinguish further the mechanisms of offset analgesia and attenuation we
      applied noxious heat resulting in an experience of low, medium or high pain to
      the volar forearm of 16 subjects comparing pain intensity ratings for increases
      and decreases in temperature, repeated over 3 days. Offset analgesia was
      consistently demonstrated but the effects of attenuation were more complex. There
      was no attenuation effect for the unchanging stimuli delivered across the 3 days
      of testing but attenuation effects enhanced the offset analgesia resulting in a
      larger offset analgesia effect on days 2 and 3. It is possible that offset
      analgesia and attenuation are mediated by inter-related mechanisms. Further
      studies might investigate whether offset analgesia involves inhibitory structures
      such as the PAG-RVM.

PMID- 18321741
TI  - Insights into homonuclear decoupling from efficient numerical simulation:
      techniques and examples.
AB  - A combination of techniques, including rational number synchronisation and pre
      diagonalisation of the time-dependent periodic Hamiltonian, are described which
      allow the efficient simulation of NMR experiments involving both magic-angle
      spinning (MAS) and RF irradiation, particularly in the important special case of
      phase-modulated decoupling sequences. Chebyshev and conventional diagonalisation
      approaches to calculating propagators under MAS are also compared, with Chebyshev
      methods offering significant advantages in cases where the Hamiltonian is large
      and time-dependent but not block-diagonal (as is the case for problems involving
      combined MAS and RF). The ability to simulate extended coupled spin systems
      efficiently allows 1H spectra under homonuclear decoupling to be calculated
      directly and compared to experimental results. Reasonable agreement is found for
      the conditions under which homonuclear decoupling is typically applied for rigid
      solids (although the increasing deviation of experimental results from the
      predictions of theory and simulation at higher RF powers is still unexplained).
      Numerical simulations are used to explore three features of these experiments:
      the interaction between the magic-angle spinning and RF decoupling, the effects
      of tilt pulses in acquisition windows and the effects of "phase propagation
      delays" on tilted axis precession. In each case, the results reveal features that
      are not readily anticipated by previous analytical studies and shed light on
      previous empirical observations.

PMID- 18321742
TI  - Rapid classification of protein structure models using unassigned backbone RDCs
      and probability density profile analysis (PDPA).
AB  - A method of identifying the best structural model for a protein of unknown
      structure from a list of structural candidates using unassigned 15N1H residual
      dipolar coupling (RDC) data and probability density profile analysis (PDPA) is
      described. Ten candidate structures have been obtained for the structural
      genomics target protein PF2048.1 using ROBETTA. 15N1H residual dipolar couplings
      have been measured from NMR spectra of the protein in two alignment media and
      these data have been analyzed using PDPA to rank the models in terms of their
      ability to represent the actual structure. A number of advantages in using this
      method to characterize a protein structure become apparent. RDCs can easily and
      rapidly be acquired, and without the need for assignment, the cost and duration
      of data acquisition is greatly reduced. The approach is quite robust with respect
      to imprecise and missing data. In the case of PF2048.1, a 79 residue protein,
      only 58 and 55 of the total RDC data were observed. The method can accelerate
      structure determination at higher resolution using traditional NMR spectroscopy
      by providing a starting point for the addition of NOEs and other NMR structural
      data.

PMID- 18321743
TI  - MK-0873, a PDE4 inhibitor, does not influence the pharmacokinetics of
      theophylline in healthy male volunteers.
AB  - BACKGROUND: MK-0873 is a novel selective phosphodiesterase-4 inhibitor, which has
      been in development for the treatment of chronic obstructive pulmonary disease
      (COPD). In this indication, theophylline is still an important treatment, despite
      its relatively small therapeutic window. In view of this, it is important to
      investigate whether MK-0873 could affect the pharmacokinetics, safety and
      tolerability of theophylline, when both drugs are given concomitantly. AIM: The
      objective of this study was to investigate the effect of multiple doses of oral
      MK-0873, a selective phosphodiesterase-4 inhibitor, on the pharmacokinetics,
      safety and tolerability profile of orally administered theophylline in healthy
      volunteers. METHODS: Eight healthy, non-smoking male subjects participated in
      this randomized, open-label, 2-period, cross-over study. In one period subjects
      received an oral dose of 2.5mg MK-0873 for 6 days co-administered with a single
      oral dose of 250 mg theophylline on day 5. The other period consisted of a single
      dose of 250 mg theophylline on day 1. In each period, blood samples were
      collected at predefined time points to evaluate theophylline pharmacokinetics.
      RESULTS: All subjects completed the study. The study medications were generally
      well tolerated and no clinically relevant changes were observed in either
      treatment periods. No significant difference was found in the AUC 0-infinity
      (77.7 vs. 83.8h ng/ml; p=0.280) and Cmax (6.70 vs. 7.77 ng/ml; p=0.125) of
      theophylline between the MK-0873+theophylline and theophylline only treatment,
      and bioequivalence was demonstrated for AUC0-infinity (geometric mean ratio with
      90% confidence interval: 0.930 (0.826, 1.047)). CONCLUSION: In this study, in a
      limited number of subjects, co-administration of oral MK-0873 did not affect the
      pharmacokinetics, safety, and tolerability of oral theophylline in non-smoking
      healthy male subjects.

PMID- 18321744
TI  - Tolerability of high cumulative doses of the HFA modulite beclomethasone
      dipropionate/formoterol combination inhaler in asthmatic patients.
AB  - The corticosteroid beclomethasone dipropionate (BDP) has been formulated with the
      long acting beta agonist formoterol (BDP/formoterol 100 microg/6 microg, Foster)
      in a single inhaler using Modulite technology. We have investigated the acute
      tolerability of high, cumulative doses of BDP/formoterol compared to formoterol
      alone and placebo. This was a double blind, 3-way cross-over comparison of 10
      puffs of BDP/formoterol 100 microg/6 microg or formoterol 6 microg or placebo
      during maintenance treatment with BDP/formoterol two puffs per day.
      Pharmacokinetics over 12h during maintenance treatment was measured on day 7.
      High cumulative doses were then administered on three separated days. Eighteen
      patients with asthma were recruited (mean FEV(1) 65% predicted). The primary
      endpoint was serum potassium over the 12h period after high doses. QTc, blood
      pressure and heart rate over 12h, and plasma lactate and glucose over 3h
      following dosing were assessed. Formoterol caused a significantly greater
      decrease in serum potassium than BDP/formoterol or placebo (difference in mean
      minimum concentrations; 0.11 and -0.15 mmol/l, respectively, p<0.05 for both
      comparisons). No significant differences in serum potassium parameters were found
      between BDP/formoterol and placebo. QTc, plasma lactate and vital signs values
      observed with the combination were not statistically different from those with
      formoterol alone. For glucose, the mean maximum increase after formoterol
      treatment was 0.4 mmol/l (p<0.01 compared to placebo), while BDP/formoterol
      treatment caused a maximum increase of 0.7 mmol/l (p<0.01 compared to formoterol
      and placebo). The active metabolite of BDP is beclomethasone-17-monopropriate
      (B17MP), which reached Cmax at 0.25 h, with an elimination half-life of 3.7 h.
      Formoterol also reached Cmax at 0.25 h, and concentrations were measurable up to
      12 h. High doses of BDP/formoterol did not significantly reduce serum potassium,
      while formoterol alone did to a greater extent. The BDP/formoterol combination
      was well tolerated, and exhibited a safety profile generally similar to
      formoterol alone when administered in high doses to stable asthmatic patients.

PMID- 18321745
TI  - Effect of topical application of raspberry ketone on dermal production of insulin
      like growth factor-I in mice and on hair growth and skin elasticity in humans.
AB  - Sensory neurons release calcitonin gene-related peptide (CGRP) on activation. We
      recently reported that topical application of capsaicin increases facial skin
      elasticity and promotes hair growth by increasing dermal insulin-like growth
      factor-I (IGF-I) production through activation of sensory neurons in mice and
      humans. Raspberry ketone (RK), a major aromatic compound contained in red
      raspberries (Rubus idaeus), has a structure similar to that of capsaicin. Thus,
      it is possible that RK activates sensory neurons, thereby increasing skin
      elasticity and promoting hair growth by increasing dermal IGF-I production. In
      the present study, we examined this possibility in mice and humans. RK, at
      concentrations higher than 1 microM, significantly increased CGRP release from
      dorsal root ganglion neurons (DRG) isolated from wild-type (WT) mice and this
      increase was completely reversed by capsazepine, an inhibitor of vanilloid
      receptor-1 activation. Topical application of 0.01% RK increased dermal IGF-I
      levels at 30 min after application in WT mice, but not in CGRP-knockout mice.
      Topical application of 0.01% RK increased immunohistochemical expression of IGF-I
      at dermal papillae in hair follicles and promoted hair re-growth in WT mice at 4
      weeks after the application. When applied topically to the scalp and facial skin,
      0.01% RK promoted hair growth in 50.0% of humans with alopecia (n=10) at 5 months
      after application and increased cheek skin elasticity at 2 weeks after
      application in 5 females (p<0.04). These observations strongly suggest that RK
      might increase dermal IGF-I production through sensory neuron activation, thereby
      promoting hair growth and increasing skin elasticity.

PMID- 18321746
TI  - A role for metallothionein in the pathogenesis of diabetes and its cardiovascular
      complications.
AB  - It has been suspected for a long time that zinc has a role in various aspects of
      diabetes, but specific molecular targets of zinc remained largely elusive. Recent
      discoveries of associations between diabetes and polymorphisms in human genes now
      suggest that proteins that control the cellular availability of zinc ions are
      involved. One protein is the zinc transporter ZnT-8 that supplies pancreatic beta
      cells with zinc. The other is metallothionein 1A, a member of a protein family
      that links zinc and redox metabolism. Changes in the availability of zinc ions
      modulate insulin signaling and redox processes. Both zinc and metallothionein
      protect cells against the redox stress that occurs in diabetes and contributes to
      its progression towards diabetic complications, including heart disease.

PMID- 18321747
TI  - Paraplegia due to non-osseous spinal tuberculosis: report of three cases and
      review of the literature.
AB  - BACKGROUND: In developing countries, a recognized etiology of paraplegia can be
      tuberculous radiculomyelitis or tuberculomas, especially in patients with
      evidence of either active or latent tuberculosis. These entities should also be
      considered in high-risk patients or in patients who have emigrated from regions
      with a high prevalence of tuberculosis (TB). Both arachnoiditis and intradural
      tuberculomas are uncommon forms of spinal TB. CASE REPORTS: We report three cases
      of TB of the spinal cord in young males with paraplegia or paraparesis who were
      hospitalized over a one-year period. The clinical presentation and clinical
      course differed among the three patients: radiculomyelitis complicating
      tuberculous meningitis for the first patient and spinal tuberculomas in the other
      two. Neuroimaging with magnetic resonance imaging (MRI) was critical for
      diagnosis. CONCLUSIONS: The therapy for spinal TB should be conservative since
      the neurologic deficits are mainly secondary to the inflammatory process. Usually
      these lesions respond to medical therapy alone, and with early diagnosis one can
      avoid unnecessary surgical intervention. In our limited clinical experience,
      corticosteroids (IV, intrathecal, or both) appear to have a beneficial effect.

PMID- 18321748
TI  - Role of interleukin-12 in determining differential kinetics of invariant natural
      killer T cells in response to differential burden of Listeria monocytogenes.
AB  - Invariant (i) natural killer (NK) T cells are unique T lymphocytes expressing NKR
      P1B/C (NK1.1), which recognize glycolipids, notably alpha-galactosylceramide
      (alpha-GalCer) presented by CD1d. The characteristic phenotype of these iNKT
      cells undergoes dramatic changes following Listeria monocytogenes infection, and
      interleukin (IL)-12 is involved in these alterations. Here we show that liver
      iNKT cells in mice are differentially influenced by the load of infection. Liver
      alpha-GalCer/CD1d tetramer-reactive (alpha-GalCer/CD1d(+)) T cells expressing
      NK1.1 became undetectable by day 2 following L. monocytogenes infection and
      concomitantly cells lacking NK1.1 increased regardless of the severity of
      infection. Whereas alpha-GalCer/CD1d(+)NK1.1(+) T cells remained virtually
      undetectable on day 4 following low-dose infection, considerable numbers of these
      cells were detected in high-dose-infected mice. Whereas numbers of IL-12
      producers in the liver on day 4 post infection were comparable in low- and high
      dose-infected mice without in vitro restimulation with heat-killed Listeria,
      those were more prominent in low-dose-infected mice than in high-dose-infected
      mice after restimulation despite the fact that higher numbers of macrophages and
      granulocytes infiltrated the liver in high-dose-infected mice than in low-dose
      infected mice. Our results indicate that NK1.1 surface expression on iNKT cells
      is differentially modulated by the burden of infection, and suggest that a high
      bacterial load probably causes loss of IL-12 production.

PMID- 18321749
TI  - Critical contribution of immunoproteasomes in the induction of protective
      immunity against Trypanosoma cruzi in mice vaccinated with a plasmid encoding a
      CTL epitope fused to green fluorescence protein.
AB  - Acquired immunity against infection with Trypanosoma cruzi is dependent on
      CD8(+)T cells. Here, to develop a vaccine strategy taking advantage of activated
      CD8(+)T cells, we constructed a DNA vaccine, designated pGFP-TSA1, encoding a
      fusion protein linking GFP to a single CTL epitope of TSA1, a leading candidate
      for vaccine against T. cruzi. C57BL/6 mice vaccinated with this plasmid showed
      suppressed parasitemia and prolonged survival. Vaccination with pGFP-TSA1
      enhanced epitope-specific cytotoxicity and IFN-gamma secretion by CD8(+)T cells.
      Furthermore, the depletion of CD8(+)T cells prior to challenge infection with T.
      cruzi completely abolished this protection, indicating that CD8(+)T cells are the
      principal effector T cells involved. When mice deficient in the proteasome
      activator PA28alpha/beta or the immunoproteasome subunits LMP2 and LMP7 were
      used, the protective immunity against infection was profoundly attenuated. Our
      findings clearly demonstrate that vaccination with pGFP-TSA1 successfully induces
      protection dependent on CD8(+)T cell activation, in which immunoproteasomes play
      a crucial role. It is noteworthy to document that physical binding of the epitope
      and GFP is required for induction of this protection, since mice vaccinated with
      pTSA1-IRES-GFP failed to acquire resistance, probably because the epitope and GFP
      are separately expressed in the antigen-presenting cells.

PMID- 18321750
TI  - A comparison of Anopheles gambiae and Plasmodium falciparum genetic structure
      over space and time.
AB  - Population genetic structure and subdivision are key factors affecting the
      evolution of organisms. In this study, we analysed and compared the population
      genetic structure of the malaria parasite Plasmodium falciparum and its mosquito
      vector Anopheles gambiae over space and time in the Nianza Province, near
      Victoria Lake in Kenya. The parasites were collected from mosquitoes caught in
      six villages separated by up to 68 km in 2002 and 2003. A total of 545 oocysts
      were dissected from 122 infected mosquitoes and genotyped at seven microsatellite
      markers. Five hundred and forty-seven mosquitoes, both infected and uninfected,
      were genotyped at eight microsatellites. For the parasite and the vector, the
      analysis revealed no (or very little) genetic differentiation among villages.
      This may be explained by high local population sizes for the parasite and the
      mosquito. The small level of genetic differentiation observed between populations
      may explain the speed at which antimalarial drug resistance and insecticide
      resistance spread into the African continent.

PMID- 18321751
TI  - [Bristow-Latarjet repairs for anterior instability of the shoulder: clinical and
      radiographic results at mean 8.2 years follow-up].
AB  - PURPOSE OF THE STUDY: We reviewed, at a mean follow-up of 8.2 years, clinical and
      radiographic results after 93 Bristow-Latarjet procedures for anterior
      instability of the shoulder. MATERIAL AND METHODS: There were 84 men and nine
      female. The average age was 23 years at the time of operative intervention. Forty
      four shoulders were on the dominant side. Eighty patients practiced sports
      activities, with 74 patients a risk sport. Seventy-seven patients have had five
      or more recurrent of dislocation of the shoulder. The operations were performed
      by a senior surgeon. Evaluation was done by a clinician, who did not perform the
      operation. Clinical outcome was assessed with the Duplay score, and the
      satisfaction of the patients. Radiographic evaluation was done using the standard
      radiography of the shoulder. RESULTS: According to the Duplay scoring system, we
      have had 30.1% of excellent results, 43% of good results, 16.1% of fair results,
      and 10.8% of poor results. The mean Duplay score was 84.7 points with 19 points
      for the return in sports, 23 points for the stability, 21 points for the pain,
      and 22 points for the movement. The loss of rotation was less than 13 degrees
      (mean). Among the patients, 57.4% returned to their former sports activities at
      the same level, with 59.8% a risk sports. Five patients reported redislocation
      and eleven patients reported apprehension. The patients were painless in 75.8%.
      Forty-four patients were very satisfied or satisfied at follow-up. At review,
      there were radiological degenerative changes in nine shoulders: six in Samilson
      grade I, one grade II, and two grade III. There was no radiological evidence of
      loosing, migration or fracture of the coracoid screws, and no nonunion. We have
      had six cases of resorption of the coracoid tip. DISCUSSION: We are aware of the
      limitation of the study. It is a retrospective study and there is no control
      group. However, we believe that, in regard of our result, the Bristow-Latarjet
      procedure for anterior glenohumeral instability is safe and effective with good
      objective and subjective result, and a high degree of patient satisfaction.
      Radiological findings do not always correlate with the functional outcome and
      patient satisfaction. CONCLUSION: Although it is a non-anatomical repair, the
      Bristow-Latarjet procedure provides desirable functional results.

PMID- 18321752
TI  - Sonochemical degradation of triclosan in water and wastewater.
AB  - The sonochemical degradation of 5 microg l(-1) triclosan, a priority micro
      pollutant, in various environmental samples (seawater, urban runoff and influent
      domestic wastewater) as well as in model solutions (pure and saline water) was
      investigated. Experiments were conducted with a horn-type sonicator operating at
      80 kHz frequency and a nominal applied power of 135 W, while solid-phase
      microextraction coupled with gas chromatography-electron capture detector
      (SPME/GC-ECD) was employed to monitor triclosan degradation. The latter followed
      pseudo-first order kinetics with the rate constant being (min(-1)): 0.2284 for
      seawater>0.1051 for 3.5% NaCl in deionised water>0.0597 for centrifuged urban
      runoff approximately 0.0523 for untreated urban runoff >0.0272 for deionised
      water >0.0063 for wastewater influent. SPME/GC-ECD and SPME coupled with gas
      chromatography-mass spectrometry (SPME/GC-MS) were also used to check for the
      formation of chlorinated and other toxic by-products; at the conditions in
      question, the presence of such compounds was not confirmed.

PMID- 18321753
TI  - Donepezil-induced jaw tremor.

PMID- 18321754
TI  - Parkinsonism associated with the homozygous W748S mutation in the POLG1 gene.
AB  - Parkinsonism has been described in patients with mutations in POLG1 gene. The
      W748S mutation is one of the most common mutations in this gene and it has been
      found to be a frequent cause of autosomal recessive ataxia in adults and the
      Alpers syndrome in children. We found the W748S mutation in a 65-year-old man
      with a late-onset syndrome consisting of ataxia, parkinsonism, ophthalmoplegia,
      peripheral neuropathy, and sensorineural hearing loss. Parkinsonism is one of the
      phenotypic features associated also with the W748S mutation.

PMID- 18321755
TI  - Adaptation to cyclic stance perturbations in Parkinson's disease depends on
      postural demands.
AB  - The postural reactions of 10 moderate PD patients and 10 age matched controls
      were studied during stance on a sinusoidally back and forth moving platform
      during 5 blocks of 10, 1-min trials. Free stance was followed by weight bearing,
      lowering or raising the center of gravity (COG) by 10%. Next, a book was balanced
      on the head and finally, forward inclination was constrained. Normal stance
      strategy, including predictive muscle responses was found during free stance.
      Modifying COG height caused little response changes. Stance strategy became
      abnormal when head trajectory or forward inclination was restricted, indicating
      that ability to generate a nonstandard multi-joint stance strategy, rather than
      production of adequate stabilizing forces, is impaired in moderate, medicated PD
      patients.

PMID- 18321756
TI  - Sympathetic sudomotor and vasoconstrictive neural function in patients with
      Parkinson's disease.
AB  - To evaluate sympathetic sudomotor and vasoconstrictive neural function in
      Parkinson's disease (PD), we simultaneously recorded sympathetic skin response
      (SSR) and skin blood flow (SVR; skin vasomotor reflex), as well as skin
      sympathetic nerve activity (SSNA) measured in peroneal nerves by
      microneurography, comparing 12 patients with idiopathic PD with 16 healthy
      controls. Resting SSNA frequency (8.8+/-4.3 bursts/min) was significantly lower
      in PD patients than in controls (p<0.01). Frequency increases in response to
      performing mental arithmetic were slightly smaller in PD patients than in
      controls. PD patients exhibited normal SSNA reflex latencies compared with
      controls. Although no significant relationship was found between resting SSNA
      frequency and disease duration or degree of disability, a significantly negative
      correlation between increases in SSNA with mental arithmetic and PD duration was
      observed. Occurrence of SSR and SVR following SSNA bursts induced by electrical
      stimuli was reduced in PD (p<0.05). In patients with PD, sympathetic sudomotor
      and vasoconstrictive neural function was decreased at rest, but SSNA reflex
      latencies in the legs were nearly normal. Since responses of peripheral target
      organs may be impaired, both central and peripheral factors may contribute to
      autonomic symptoms in PD.

PMID- 18321757
TI  - Clinical features at first visit and rapid disease progression in Parkinson's
      disease.
AB  - We report a retrospective multivariable analysis of the association between
      patient characteristics at first clinic visit and rapid disease progression in
      1411 Parkinson's disease patients treated between 1985 and 2006. At first visit
      rapid progression was positively associated with age at onset > or = 70 years
      (OR=5.77), rigidity (OR=1.94), bradykinesia (OR=1.73), dementia (OR=2.61), and
      levodopa use (OR=1.74). Rapid progression was negatively associated with disease
      duration (OR=0.52), male sex (OR=0.49), and resting tremor at first visit
      (OR=0.44). Family history of movement disorders, while significant for
      univariable analysis, did not retain significance in multivariable analysis. This
      initial clinical profile may aid physicians in adjusting treatment and follow-up
      plans. Further prospective studies are needed to evaluate this relationship.

PMID- 18321758
TI  - Investigation of genes related to familial forms of Parkinson's disease--with
      focus on the Parkin gene.

PMID- 18321759
TI  - Uric acid associates with cognition in Parkinson's disease.
AB  - Cognitive dysfunction is common in Parkinson's disease (PD). Low plasma uric acid
      level is a risk factor for PD but its association with cognitive impairment in PD
      has not been previously studied. In the present study urine uric acid level as
      well as plasma uric acid- and homocysteine levels were measured in 40 patients
      with PD. Comprehensive neuropsychological tests including computerized tasks were
      performed on all. Both low plasma and low urine uric acid levels associated with
      decreased neuropsychological performance. In multiple linear regression low urine
      uric acid level predicted worse performance in the Picture completion subtest of
      the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (p=0.003) and in the Rule
      shift cards test of the Behavioral Assessment of the Dysexecutive Syndrome (BADS)
      (p=0.04). Low plasma uric acid level predicted worse performance both in the
      Picture completion (p=0.02) and Similarities subtest of the WAIS-R (p=0.02).
      Reaction time and the time spent on cognitive processing in the Statement
      verification task were inversely correlated with the uric acid levels (p=0.0001).
      There was no correlation between the homocysteine level and neuropsychological
      performance. Instead, the plasma uric acid and homocysteine levels correlated
      significantly and their possible association in PD is discussed.

PMID- 18321760
TI  - Olfactory tests in the diagnosis of essential tremor.
AB  - Most patients with tremor-dominant Parkinson's disease (PD) have impaired smell
      function but it is unclear whether this is true for subjects with essential
      tremor (ET). If ET patients do not exhibit meaningful smell loss, then olfactory
      testing may help to distinguish PD from ET. We assessed olfactory function in 59
      ET and 64 tremor-dominant PD patients using the University of Pennsylvania Smell
      Identification Test (UPSIT) and olfactory event-related potential (OERP). UPSIT
      scores were compared to those from 245 healthy controls, and OERPs were compared
      to those from 74 controls. Unlike the PD test scores, those of ET patients were
      indistinguishable from controls when the effects of age, age of onset, gender,
      and smoking were taken into account. ET patients with a family history of tremor
      scored significantly better than controls on the UPSIT, and their rate of decline
      with age was slower. The effect was not observed on OERP. Smell testing may help
      to distinguish between ET and tremor-predominant PD, and patients with family
      history of tremor may represent a subgroup whose olfactory function is enhanced
      by some unknown mechanism.

PMID- 18321761
TI  - Paradigm shifters, professionals, and community sentinels: immigrant community
      institutions' roles in shaping places and implications for stigmatized public
      health initiatives.
AB  - Immigrant community institutions are strategically positioned to facilitate or
      impede public health efforts in their neighborhoods and communities because of
      their influence over discourse regarding values and tradition. Their authority
      may be particularly relevant when stigmatized or sensitive issues, such as HIV or
      reproductive health, are addressed. Using qualitative and quantitative methods to
      analyze data collected from 22 Chinese and South Asian immigrant institutions in
      New York City, we examine attitudes about HIV, social change and tradition to
      delineate the different structural roles that Asian immigrant community
      institutions play in relation to the preservation of traditional values and
      culture in their neighborhoods and communities. Implications are explored for
      working with immigrant community institutions to conduct HIV-related work and
      other stigmatized public health initiatives in immigrant neighborhoods.

PMID- 18321762
TI  - Hepatitis C virus core protein: its coordinate roles with PA28gamma in metabolic
      abnormality and carcinogenicity in the liver.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver diseases, including
      steatosis, cirrhosis and hepatocellular carcinoma, and epidemiological studies
      indicate that HCV is also associated with insulin resistance and type 2 diabetes
      mellitus. The HCV core protein is not only a viral structural component but also
      a pathogenic factor, since its expression leads to the development of liver
      steatosis, insulin resistance and hepatocellular carcinoma in mice. The nuclear
      proteasome activator PA28gamma/REGgamma, which specifically binds to the core
      protein, is required for the virulence of the core protein. Elucidation of the
      mechanisms by which HCV core protein participates in the above conditions may
      provide clues toward the development of novel therapeutic measures for chronic
      hepatitis C.

PMID- 18321763
TI  - Thrombospondin-1 enhances human thyroid carcinoma cell invasion through urokinase
      activity.
AB  - Previous studies reported that modification in the expression of the
      matricellular multidomain glycoprotein thrombospondin-1 (TSP-1) could play a
      critical role in the control of tumor progression and metastasis development. The
      function of this multimodular protein in cancers appears highly dependent on the
      cellular context and thus remains to date very difficult to accurately
      characterize. Controversial results indeed exist reporting either pro- or anti
      invasive properties of TSP-1. Since it appeared that TSP-1 could be of prognostic
      value for certain specific types of cancers, we examined in this study the
      prospective function of TSP-1 in the control of human follicular thyroid
      carcinoma (FTC) cell invasiveness. First, we established that the aggressive
      behavior of human thyroid malignant cells is closely correlated to the TSP-1
      amount. We demonstrated that exogenously added TSP-1 stimulates by two-fold the
      capacity of FTC cells to invade Matrigel-coated wells. The use of specific anti
      TSP-1 blocking antibodies led to a drastic inhibition of the basal FTC cell
      invasion. Zymography experiments revealed that the uPA-dependent proteolytic
      activity is directly controlled by TSP-1, MMPs activity is not. The TSP-1
      mediated stimulation of uPA appears to occur at post-transcriptional level.
      Finally, we established that the TSP-1-stimulated FTC cell invasion is wholly
      abolished under anti-uPA blocking antibodies or aprotinin treatments whereas MMP
      inhibitors have no effect. All together, we evidenced in the present study that
      TSP-1 promotes human follicular thyroid carcinoma cell invasion mainly through up
      regulation of the urokinase-dependent activity.

PMID- 18321764
TI  - Expression and localisation of the essential copper transporter DmATP7 in
      Drosophila neuronal and intestinal tissues.
AB  - Copper homeostasis is achieved by a combination of regulated uptake, efflux and
      sequestration and is essential for animal health and viability. Transmembrane
      copper transport proteins of the P-type ATPase family play key roles in cellular
      copper efflux. Here, the transcriptional and post-translational regulation of
      DmATP7, the sole Drosophila melanogaster ortholog of the human MNK and WND copper
      transport genes, is examined. An enhancer element with sufficient regulatory
      information to rescue DmATP7 mutant flies to adulthood is identified. This
      regulatory element drives expression in all neuronal tissues examined and
      demonstrates copper-inducible, Mtf-1 dependent expression in the larval midgut.
      These results support an important functional role for copper transport in
      neuronal tissues and indicate that regulation of DmATP7 expression is not used to
      limit copper absorption in toxic copper conditions. Localisation of a functional
      EYFP-DmATP7 fusion protein is also examined. This fusion protein localises at or
      proximal to the basolateral membrane of DmATP7 expressing midgut cells supporting
      a role for DmATP7 in export of copper from midgut cells.

PMID- 18321765
TI  - Interferon and cytokine responses to SARS-coronavirus infection.
AB  - The sudden emergence of severe acute respiratory syndrome (SARS) has boosted
      research on innate immune responses to coronaviruses. It is now well established
      that the causative agent, a newly identified coronavirus termed SARS-CoV, employs
      multiple passive and active mechanisms to avoid induction of the antiviral type I
      interferons in tissue cells. By contrast, chemokines such as IP-10 or IL-8 are
      strongly upregulated. The imbalance in the IFN response is thought to contribute
      to the establishment of viremia early in infection, whereas the production of
      chemokines by infected organs may be responsible for (i) massive immune cell
      infiltrations found in the lungs of SARS victims, and (ii) the dysregulation of
      adaptive immunity. Here, we will review the most recent findings on the
      interaction of SARS-CoV and related Coronaviridae members with the type I
      interferon and cytokine responses and discuss implications for pathogenesis and
      therapy.

PMID- 18321766
TI  - A 10-year follow up of ocular hypertensive patients within the Bolton Corneal
      Thickness Study. Can measured factors predict prognostic outcomes?
AB  - OBJECTIVE: This is a case note review of a cohort of patients examining the
      effects of central corneal thickness (CCT), presenting intraocular pressure
      (IOP), age and gender on the risk of progression of ocular hypertension (OHT) to
      primary glaucoma (POAG) over a 10-year period. DESIGN: Cohort study with
      retrospective case note review. PARTICIPANTS AND METHODS: 58 case notes from a
      cohort at the Bolton Royal Infirmary initially assessed 10 years ago were
      reviewed again. Presenting CCT, IOP, age and gender were recorded. Development of
      POAG was assessed by visual field and/or optic disc changes being present. MAIN
      OUTCOME MEASURES: The effects of CCT, IOP, age and gender on the risk of
      progression of OHT to POAG were analysed in a multivariate logistic regression
      model following a preliminary univariate analysis. RESULTS: 50 out of 116 eyes
      developed primary open angle glaucoma over the 10-year period. Thinner CCT (odds
      ratio 0.985 associated with each 1mum increase in CCT), higher presenting IOP
      (odds ratio 1.131 associated with each 1mmHg increase in IOP) and increasing age
      (odds ratio 1.062 associated with each 1 year increase in age) were found to be
      associated with progression to POAG. CONCLUSION: Patients with a CCT of 579microm
      or more, a presenting intraocular pressure of 26mmHg or less and age 75 years or
      less had a lower risk of developing POAG within this cohort of patients.

PMID- 18321767
TI  - Anterior segment OCT-based diagnosis and management of retained Descemet's
      membrane following penetrating keratoplasty.
AB  - PURPOSE: To report a case of retained Descemet's membrane after penetrating
      keratoplasty for congenital hereditary endothelial dystrophy (CHED) documented by
      anterior segment optical coherence tomography and review of literature. METHODS:
      Case report and review of literature. RESULTS: A 14-year-old boy underwent
      penetrating keratoplasty for CHED. A retained host Descemet's membrane was
      detected with a supernumerary anterior chamber on the first postoperative day.
      The retained Descemet's membrane was documented using slit lamp adapted anterior
      segment optical coherence tomography (SLOCT). Surgical intervention for the
      Descemet's membrane removal was done in the third postoperative week. The
      complete removal of the membrane was confirmed on SLOCT. CONCLUSION: Inadvertent
      retention of the host Descemet's membrane is a rare but possible complication in
      penetrating keratoplasty for CHED. Proper anticipation, early detection and
      removal will help in preventing any undue risk of graft failure.

PMID- 18321768
TI  - Versatile protection from mutagenic DNA lesions conferred by bipartite
      recognition in nucleotide excision repair.
AB  - Nucleotide excision repair is a cut-and-patch pathway that eliminates potentially
      mutagenic DNA lesions caused by ultraviolet light, electrophilic chemicals,
      oxygen radicals and many other genetic insults. Unlike antigen recognition by the
      immune system, which employs billions of immunoglobulins and T-cell receptors,
      the nucleotide excision repair complex relies on just a few generic factors to
      detect an extremely wide range of DNA adducts. This molecular versatility is
      achieved by a bipartite strategy initiated by the detection of abnormal strand
      fluctuations, followed by the localization of injured residues through an
      enzymatic scanning process coupled to DNA unwinding. The early recognition
      subunits are able to probe the thermodynamic properties of nucleic acid
      substrates but avoid direct contacts with chemically altered bases. Only
      downstream subunits of the bipartite recognition process interact more closely
      with damaged bases to delineate the sites of DNA incision. Thus, consecutive
      factors expand the spectrum of deleterious genetic lesions conveyed to DNA repair
      by detecting distinct molecular features of target substrates.

PMID- 18321769
TI  - Studies on crystal growth, vibrational and optical properties of organic
      nonlinear optical crystal: p-aminoazobenzene.
AB  - p-Aminoazobenzene (p-AAZB), an organic nonlinear optical (NLO) crystal having
      good optical quality has been grown by slow evaporation solution technique using
      ethanol as a solvent. Solubility studies were performed at different
      temperatures. The structural characterization of the grown crystals was carried
      out by X-ray diffraction. Group theoretical analysis was carried out to calculate
      the number of modes of vibration. The lowering of the wave numbers of azo group
      suggests the existence of strong intermolecular N-H...H hydrogen bonding. This
      has been analysed based on the vibrational spectral features. Optical absorption
      studies show the effective transmission in the entire UV-vis region. The second
      harmonic generation results show the suitability of this material for NLO
      applications.

PMID- 18321770
TI  - Luminescent and magnetic Fe3O4/Py/PAM nanocomposites for the chromium(VI)
      determination.
AB  - A novel luminescent and magnetic Fe(3)O(4)/pyrene/polyacrylamide
      (Fe(3)O(4)/Py/PAM) nanocomposite has been prepared under ultrasonic radiation.
      This magnetic nanocomposite combined with pyrene would lead to a special
      functional magnetic luminescent composite that enjoys both the advantages of
      magnetic nanoparticles of Fe(3)O(4) and fluorescence nanoparticles of pyrene.
      Taking advantage of the magnetic property of Fe(3)O(4) nanocomposites, we can
      separate Fe(3)O(4)/Py/PAM nanocomposites from solution easily just by using a
      permanent magnet. Based on the fluorescence quenching of Fe(3)O(4)/Py/PAM
      nanocomposites by Cr(VI), a method for the selective determination of Cr(VI),
      without separation of Cr(III) in water, was developed. Under optimal experimental
      conditions, a limit of detection of 0.01 microg mL(-1) was achieved. The
      calibration curve was linear over the concentration range of 0.1-14.0 microg mL(
      1) with a correlation coefficient of 0.9975. The proposed method has been applied
      to the selective quantification of Cr(VI) in synthetic samples and wastewater
      samples with the satisfactory results.

PMID- 18321771
TI  - Molecular structure, spectroscopic studies and first-order molecular
      hyperpolarizabilities of p-amino acetanilide.
AB  - The infrared absorption, Raman spectra and SERS spectra of p-amino acetanilide
      have been analyzed with the aid of density functional theory calculations at
      B3LYP/6-311G(d,p) level. The electric dipole moment (mu) and the first
      hyperpolarizability (beta) values of the investigated molecule have been computed
      using ab initio quantum mechanical calculations. The calculation results also
      show that the synthesized molecule might have microscopic nonlinear optical (NLO)
      behavior with non-zero values. Computed geometries reveal that the PAA molecule
      is planar, while secondary amide group is twisted with respect to the phenyl ring
      is found, upon hydrogen bonding. The hyperconjugation of the C=O group with
      adjacent C-C bond and donor-acceptor interaction associated with the secondary
      amide have been investigated using computed geometry. The carbonyl stretching
      band position is found to be influenced by the tendency of phenyl ring to
      withdraw nitrogen lone pair, intermolecular hydrogen bonding, conjugation and
      hyperconjugation. The existence of intramolecular C=O...H hydrogen bonded have
      been investigated by means of the natural bonding orbital (NBO) analysis. The
      influence of the decrease of N-H and C=O bond orders and increase of C-N bond
      orders due to donor-acceptor interaction has been identified in the vibrational
      spectra. The SERS spectral analysis reveals that the large enhancement of in
      plane bending, out of plane bending and ring breathing modes in the surface
      enhanced Raman scattering spectrum indicates that the molecule is adsorbed on the
      silver surface in a 'atleast vertical' configuration, with the ring perpendicular
      to the silver surface.

PMID- 18321772
TI  - Spectrofluorimetric determination of zinc using 8-hydroxy-7-(4-sulfo-1
      naphthylazo)-5-quinoline sulfonic acid.
AB  - A sensitive and a selective spectrofluorimetric method have been developed for
      the rapid determination of zinc. The method is based on the complex formation
      between zinc and 8-hydroxy-7-(4-sulfo-1-naphthylazo)-5-quinoline sulfonic acid
      (HSNQ). The optimum conditions for the complex formation were metal to ligand
      stoichiometric ratio of 1:1 at pH 8.0 with 0.2M acetate buffer. The fluorescence
      of the complex is monitored at an emission wavelength of 545 nm with excitation
      at 360 nm. Under these conditions linear calibration curves were obtained from 50
      ppb to 400 ppb. The detection limit was 7 ppb. The maximum relative standard
      deviation of the method was 2% for water samples, 4% for milk samples and 7% for
      hair samples (n = 5). The method was successfully applied for the determination
      of zinc in drinking water, hair and milk samples. The results were found to be in
      good agreement with those obtained by flame atomic absorption spectrophotometric
      methods. The t-test and F-test indicated no significant difference at 95%
      confidence level.

PMID- 18321773
TI  - Spectrofluorimetric study on the inclusion interaction between vitamin K3 with p
      (p-sulfonated benzeneazo)calix[6]arene and determination of VK3.
AB  - The characteristics of host-guest complexation between p-(p-sulfonated
      benzeneazo) calix[6]arene (SBC6A) and vitamin K3 (VK3) were investigated by
      fluorescence spectrometry. A 1:1 stoichiometry for the complexation was
      established and was verified by Job's plot. An association constant of 4.95 x
      10(3)L mol(-1) at 20 degrees C was calculated by applying a deduced equation. The
      interaction mechanism of the inclusion complex was discussed. It was found that
      the fluorescence of SBC6A could be remarkably quenched by an appropriate amount
      of VK3 especially when non-ionic surfactant Triton X-100 existed. According to
      the obtained results, a novel sensitive spectrofluorimetric method for the
      determination of VK3 based on supramolecular complex was developed with a linear
      range of 5.0 x 10(-7) -3.0 x 10(-5)mol L(-1) and a detection limit of 2.0 x 10(
      7)mol L(-1). The proposed method was used to determine VK3 in commercial
      preparations with satisfactory results.

PMID- 18321774
TI  - Anomalous hygroscopic growth of fine particles of MgSO4 aerosols investigated by
      FTIR/ATR spectroscopy.
AB  - This paper demonstrates an approach for investigating the hygroscopic growth of
      MgSO4 aerosols deposited on ZnSe substrate by using attenuated total reflection
      Fourier transform infrared (FTIR/ATR) spectroscopy. The experimental setup based
      upon a refitted standard FTIR/ATR accessory was adopted for the hygroscopic study
      of aerosols. It has been found that the "predeliquescence" of fine MgSO4 aerosol
      particles with the mean spreading diameter around 500 nm occurred before roughly
      15% RH. In contrast, the abrupt water absorption of coarse MgSO4 particles with
      the mean diameter larger than about 10 microm was reported to occur at roughly
      42% RH, which was reproduced in this study. Up to now, both theoretical and
      experimental investigations were rare and immature for fine particles, but the
      method we used in this study worked very well for the fine particles of MgSO4
      aerosols. It has been found that the possible reason for the "predeliquescence"
      fine particles of MgSO4 aerosols is that the initial state or phase of fine
      particles is different from coarse ones after desiccation. This research
      demonstrates that the approach based on the ATR technique is very convenient,
      accurate and requires only a little amount of lab supplies.

PMID- 18321775
TI  - Modeling the Arden Syntax for medical decisions in XML.
AB  - PURPOSE: A new model expressing Arden Syntax with the eXtensible Markup Language
      (XML) was developed to increase its portability. METHODS: Every example was
      manually parsed and reviewed until the schema and the style sheet were considered
      to be optimized. When the first schema was finished, several MLMs in Arden Syntax
      Markup Language (ArdenML) were validated against the schema. They were then
      transformed to HTML formats with the style sheet, during which they were compared
      to the original text version of their own MLM. When faults were found in the
      transformed MLM, the schema and/or style sheet was fixed. This cycle continued
      until all the examples were encoded into XML documents. The original MLMs were
      encoded in XML according to the proposed XML schema and reverse-parsed MLMs in
      ArdenML were checked using a public domain Arden Syntax checker. RESULTS: Two
      hundred seventy seven examples of MLMs were successfully transformed into XML
      documents using the model, and the reverse-parse yielded the original text
      version of MLMs. Two hundred sixty five of the 277 MLMs showed the same error
      patterns before and after transformation, and all 11 errors related to statement
      structure were resolved in XML version. The model uses two syntax checking
      mechanisms, first an XML validation process, and second, a syntax check using an
      XSL style sheet. CONCLUSION: Now that we have a schema for ArdenML, we can also
      begin the development of style sheets for transformation ArdenML into other
      languages.

PMID- 18321776
TI  - Nucleic acid testing (NAT) for HCV RNA in Italian transfusion centres: an
      external quality assessment.
AB  - BACKGROUND: We conducted an external quality assessment of the results obtained
      in Italian transfusion centre laboratories employing nucleic acid testing (NAT)
      for detection of HCV RNA in donated blood. STUDY DESIGN: Of 110 transfusions
      centres in Italy, 101 voluntarily participated. Each laboratory received seven
      separate shipments of samples for HCV RNA testing by NAT. Each shipment contained
      8 plasma samples for a total of 23 negative and 33 positive samples with viral
      loads ranging from 25 to 1000 IU/mL. RESULTS: Of the 2080 HCV RNA-negative
      samples, 14 (0.7%) were reported as positive. The highest percent of false
      negative results (6.9%) was found on samples from the first shipment with viral
      loads from 75 to 100 IU/mL. In subsequent shipments, the highest false-negative
      percentage ranged from 0.6% for samples with viral loads of 170-1000 IU/mL to
      3.4% for samples with viral loads of 35-50 IU/mL. A false-negative rate of 4.9%
      occurred in samples in the sixth shipment with the lowest viral load (25IU/mL).
      Five (4.9%) centres were identified as having laboratories with low-performance.
      There were no significant differences among genotypes 1b, 2c and 3a with respect
      to percent of false-negative results reported. CONCLUSIONS: Overall, the accuracy
      of NAT observed in this study of Italian transfusion centre laboratories was
      excellent for all HCV genotypes tested, even for samples with low HCV RNA titres.

PMID- 18321777
TI  - Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in
      mice.
AB  - BACKGROUND: Cardiac inflammation and generation of oxidative stress are known to
      contribute to doxorubicin (Dox)-induced cardiomyopathy. Toll-like receptors
      (TLRs) are a part of the innate immune system and are involved in cardiac stress
      reactions. Since TLR4 might play a relevant role in cardiac inflammatory
      signalling, we investigated whether or not TLR4 is involved in Dox-induced
      cardiotoxicity. METHODS AND RESULTS: Five days after a single injection of Dox
      (20 mg/kg; i.p.), left ventricular pressure-volume loops were measured in wild
      type and TLR4-deficient mice (TLR4-/-) Dox-treated and control mice. Analyses of
      possible pathophysiological mechanisms were performed in left ventricular tissue
      and isolated myocytes, respectively. Dox injection resulted in an impairment of
      left ventricular function and neurohumoral activation, indexed by increased ET-1
      expression. This was further associated with an increase in cardiac oxidative
      stress, inflammation and apoptosis, as indicated by an up-regulation of cardiac
      lipid peroxidation, TNF-alpha expression and enhanced content of TUNEL-positive
      cells. In contrast, TLR4-/- Dox mice showed improved left ventricular function
      with reduced oxidative and inflammatory stress response including reduced cardiac
      apoptosis. These results were found to be associated with an increase of GATA-4
      expression. CONCLUSIONS: TLR4 deficiency improves left ventricular function and
      attenuates pathophysiological key mechanisms in Dox-induced cardiomyopathy.

PMID- 18321778
TI  - Quality of life in patients with chronic heart failure and Cheyne-Stokes
      respiration.

PMID- 18321779
TI  - The past and present classification problem with nanoflagellates exemplified by
      the genus Monas.

PMID- 18321781
TI  - Cancer information needs of people with intellectual disability: a review of the
      literature.
AB  - The lifespan of people with an intellectual disability has increased
      significantly in recent years; however, this has resulted in a rising incidence
      of age-related illnesses including cancer. The World Health Organisation has
      expressed concern as evidence suggests prevalence rates for cancer are increasing
      for this group. The needs of people with a cancer diagnosis and an intellectual
      disability are beginning to be highlighted; however, there appears to be a
      substantial dearth of services including appropriate cancer information. This
      presents alarming obstacles and barriers to high-quality cancer care impacting on
      treatment, management and overall survival rates for this client group.
      Furthermore, a number of policy and research reports directed at the health needs
      of people with an intellectual disability have continually highlighted the need
      for accessible information and effective communication. Having access to cancer
      information should be considered a crucial part of providing optimum holistic
      care for this client group. Cancer professionals should assess the unique
      information needs of people with an intellectual disability as mainstream
      information does not meet their requirements. Furthermore, health professionals
      working in intellectual disability settings must also address their knowledge and
      information deficits in this regard. This paper presents a review of the
      literature with a specific focus on the cancer information needs of people with
      an intellectual disability.

PMID- 18321782
TI  - Ca(2+) and insulin-mediated glucose uptake.
AB  - Insulin stimulates glucose uptake in striated muscle and fat via a complex
      cascade of signaling events. Insulin resistance in these tissues and type 2
      diabetes constitute major and rapidly increasing health problems in society.
      Recent research implicates an important role of Ca(2+) in insulin-mediated
      glucose uptake. Maneuvers that increase or decrease Ca(2+) influx also increase
      or decrease insulin-mediated glucose uptake both in normal and insulin-resistant
      cells. Ca(2+) appears to act on late steps in the insulin-signaling cascade, that
      is, the docking and fusion of glucose transporter 4 (GLUT4) vesicles with the
      plasma membrane. No Ca(2+) sensor in this process has yet been explicitly
      identified but recent studies point at synaptotagmin VII and the motor protein
      Myo1c as possible candidates.

PMID- 18321783
TI  - Disseminated disease severity as a measure of virulence of Mycobacterium
      tuberculosis in the guinea pig model.
AB  - Virulence is the measure of pathogenicity of a microorganism as determined by its
      ability to invade host tissues and to produce severe disease. In the low-dose
      aerosol guinea pig model the virulence of multiple strains of Mycobacterium
      tuberculosis was determined by measuring time of survival, bacterial loads in
      target organs, and the severity of pulmonary and extra-pulmonary lesions. Erdman
      K01, CSU93/CDC1551 and HN878 had shorter survival times compared to the common
      laboratory strain H37Rv. After 30 days of the infection bacilli had disseminated
      from the lungs resulting in microscopically visible lesions in peribronchial
      lymph nodes, peripancreatic lymph nodes, spleen, liver, pancreas, adrenal and
      heart. The extent of the lesion necrosis paralleled virulence when survival times
      were used as a measure as Erdman K01 and the two clinical isolates caused more
      necrosis and resulted in sooner death in infected animals than the H37Rv. The
      extent of extra-pulmonary lesion necrosis was a better predictor of virulence
      than the number of viable bacilli in the tissue. Overall, this study emphasizes
      the point that extra-pulmonary disease is a prominent feature of the guinea pig
      model and dissemination to organs not normally assayed such as the heart and
      adrenal glands should be taken into account in the assessment of the disease
      process.

PMID- 18321784
TI  - Effects of uridine on kindling.
AB  - The anticonvulsant effect of the nucleoside uridine has been studied for several
      decades with controversial results. One of its attractive properties is that as a
      natural endogenous molecule, it lacks the serious side effects of common
      antiepileptic drugs used today. In the current study, we examined the potential
      antiepileptogenic effect of uridine in the hippocampal kindling model, using once
      daily stimulations. Uridine was administered once or three times daily;
      levetiracetam was administered as a positive control; and normal saline was used
      as a negative control. Rats receiving uridine or levetiracetam had slower
      kindling rates and shorter afterdischarge durations than the normal saline
      controls. These results are consistent with previous work using a rapid kindling
      model and suggest that uridine has antiepileptogenic properties. Because of its
      combination of low toxicity and efficacy, uridine is a possible candidate for the
      treatment of epilepsy.

PMID- 18321785
TI  - Different physiological roles of serum leptin in the regulation of energy intake
      and thermogenesis between pregnancy and lactation in primiparous Brandt's voles
      (Lasiopodomys brandtii).
AB  - Reproduction, especially lactation, is associated with major metabolic adaptive
      changes. In this study, we investigated the metabolic changes and the roles of
      leptin during different periods of reproduction in primiparous Brandt's voles
      (Lasiopodomys brandtii). Energy intake, thermogenic capacity and serum leptin
      levels were examined in non-reproductive, mid pregnant, late pregnant, early
      lactating and peak lactating voles. Voles increased body mass by nearly 70%
      during late pregnancy compared to the non-breeding controls. The increase in body
      mass was mainly due to the increase in body fat mass which increased by 56%, and
      the growth of the reproductive tissues and digestive organs. Lactating voles
      decreased body fat by nearly 27% at peak lactation compared to the controls, and
      53% compared to late pregnant voles. At the same time they increased food intake
      significantly. Uncoupling protein 1 (UCP1) content in brown adipose tissue (BAT)
      decreased significantly at peak lactation. Serum leptin increased significantly
      in the mid pregnancy, at a time when there was no increase in body fat, and
      remained at this high level in late pregnancy. Leptin levels decreased after
      parturition and reached a nadir at peak lactation. Serum leptin was negatively
      correlated with energy intake during lactation, but not during pregnancy. These
      data suggest that Brandt's voles adjust energy intake, thermogenic capacity and
      body reserves to match the high energy demands for reproduction. Hyperleptinemia,
      without decreased energy intake suggests a state of leptin resistance during
      pregnancy, and hypoleptinemia during lactation might act as a signal to stimulate
      energy intake.

PMID- 18321786
TI  - Automated extraction of decision rules for leptin dynamics--a rough sets
      approach.
AB  - A significant area in the field of medical informatics is concerned with the
      learning of medical models from low-level data. The goals of inducing models from
      data are twofold: analysis of the structure of the models so as to gain new
      insight into the unknown phenomena, and development of classifiers or outcome
      predictors for unseen cases. In this paper, we will employ approach based on the
      relation of indiscernibility and rough sets theory to study certain questions
      concerning the design of model based on if-then rules, from low-level data
      including 36 parameters, one of them leptin. To generate easy to read, interpret,
      and inspect model, we have used ROSETTA software system. The main goal of this
      work is to get new insight into phenomena of leptin levels while interplaying
      with other risk factors in obesity.

PMID- 18321787
TI  - Effect of eradication of Helicobacter pylori on the histology and cellular
      phenotype of gastric intestinal metaplasia.
AB  - BACKGROUND & AIMS: Eradication of Helicobacter pylori appears to reduce gastric
      cancer incidence. We examined the effect of successful H pylori therapy on
      histology, phenotype of gastric intestinal metaplasia (GIM) (complete vs
      incomplete), and expression of several biomarkers related to carcinogenesis.
      METHODS: Ninety-six H pylori-positive patients from Japan were treated
      successfully and followed up prospectively over 4 years with yearly endoscopy and
      were classified into 3 groups: group CG, chronic gastritis without GIM (n = 36);
      group IM, chronic gastritis with GIM (n = 33); group DYS, and GIM with
      dysplasia/cancer in a different location of the stomach (n = 27). A total of 288
      endoscopic procedures were performed. Histology, mucin-histochemistry, and
      immunoperoxidase assays using monoclonal antibodies (mAbs) for cell phenotype
      (monoclonal antibody Das-1/colonic) and for neoplasia (TC22 and p53) were
      performed. RESULTS: The GIM histologic score was higher in group DYS than in
      group IM (P < .05) and group CG (P < .0001). The GIM scores did not change in
      groups IM and DYS over 4 years. mAb Das-1 reactivity was higher in group DYS
      (63%) than in group IM (39%) and group GC (0%). After eradication of H pylori,
      mAb Das-1 reactivity disappeared in 40% of patients (P < .0001) despite the
      unchanged GIM scores, and regression of TC22-4 was noted in the same patients.
      CONCLUSIONS: H pylori eradication does not reduce the histologic GIM score, but
      changes the cellular phenotype of GIM. This change of phenotype may be an
      important factor in the reduction of cancer incidence after eradication of H
      pylori.

PMID- 18321788
TI  - Is there still a role for double-contrast barium enema examination?
AB  - The role of double-contrast barium enema examination (DCBE) in screening for
      colorectal carcinoma has evolved considerably in recent years. This review will
      discuss the current indications for DCBE and contrast fluoroscopy of the colon
      and the anticipated future role of these studies.

PMID- 18321789
TI  - Detection of jejunal carcinoid in a patient with obscure-overt gastrointestinal
      bleeding by double-balloon enteroscopy.

PMID- 18321790
TI  - Image of the month. Portal hypertension as a result of extramedullary
      hematopoiesis caused by idiopathic myelofibrosis.

PMID- 18321791
TI  - Effects of fitness and age on the response to vagotonic atropine.
AB  - Previous work indicates compromised cardiac vagal control plays a prominent role
      in reducing arterial baroreflex gain with age, however older fit individuals
      display cardiovagal baroreflex responses similar to young individuals. The
      purpose of this study was to test the hypothesis that chronic aerobic exercise
      mitigates against age-related declines in cardiac parasympathetic receptor
      function. In forty-four young and old (fit and unfit) individuals, we used the
      parasympathomimetic responses to low doses of atropine to probe cardiac
      cholinergic receptor responses. Data were collected before and after eight doses
      of atropine sulfate from 0.4 to 7.2 microg/kg. Chronotropic responses were
      assessed from average RR intervals and heart rate variabilities were derived in
      time and frequency domains. All subjects exhibited bradycardia with at least one
      dose of atropine and peak bradycardia occurred at a similar dose in each group.
      However, changes in heart rate variability did not consistently track the
      chronotropic responses within subjects (r-square from 0.90 down to 0). As
      expected, basal RR interval was longer in the fit groups and was unaffected by
      age. However, the degree of RR interval lengthening with parasympathomimetic
      atropine was unaffected by physical fitness and was significantly less in all
      older subjects. These data indicate there are certain prepotent age-related
      declines in the cardiac parasympathetic system that cannot be prevented by
      regular physical activity.

PMID- 18321792
TI  - Dynamic expression of the RNA-binding protein Sam68 during mouse pre-implantation
      development.
AB  - The STAR protein Sam68 (KHDRBS1) is involved in several aspects of post
      transcriptional mRNA metabolism. Herein, we have investigated the expression and
      subcellular localization of Sam68 during early mouse embryogenesis. We found that
      mouse oocytes express high levels of Sam68 mRNA, low levels of the transcript for
      Khdrbs2 (current symbol for Slm-1) and no Khdrbs3 (current symbol for Slm-2), two
      highly homologous STAR genes. Sam68 protein is expressed throughout oocyte
      meiotic maturation and early embryogenesis. It is released in the cytoplasm upon
      meiotic resumption and it slowly accumulates in the nucleus after fertilization.
      Unlike what was observed for other RNA-binding proteins, nuclear accumulation of
      Sam68 was independent of de novo mRNA transcription. However, we found that
      inhibition of mRNA translation by either cycloheximide or puromycin in one-cell
      embryos caused the accumulation of Sam68 in cytoplasmic granules. Analysis of
      these granules by deconvolution microscopy demonstrated that they are sites of
      accumulation for proteins involved in the initiation of mRNA translation, such as
      eIF4A1, eIF4E and eIF4G. These granules contained RNA and were dissolved by
      treatment with RNase A. Other proteins expressed by the zygote, like the splicing
      factor SC35 or the cytoplasmic kinase ERK2, did not accumulate in such structures
      after treatment with inhibitors of mRNA translation, indicating that the
      localization of Sam68 and of the translation initiation factors in these granules
      is a specific event. These results indicate that Sam68 is involved in
      translational regulation of maternal mRNAs in the zygote and in the early
      signaling events triggered by fertilization.

PMID- 18321793
TI  - Pathogenomics: an updated European Research Agenda.
AB  - The emerging genomic technologies and bioinformatics provide novel opportunities
      for studying life-threatening human pathogens and to develop new applications for
      the improvement of human and animal health and the prevention, treatment, and
      diagnosis of infections. Based on the ecology and population biology of pathogens
      and related organisms and their connection to epidemiology, more accurate typing
      technologies and approaches will lead to better means of disease control. The
      analysis of the genome plasticity and gene pools of pathogenic bacteria including
      antigenic diversity and antigenic variation results in more effective vaccines
      and vaccine implementation programs. The study of newly identified and
      uncultivated microorganisms enables the identification of new threats. The
      scrutiny of the metabolism of the pathogen in the host allows the identification
      of new targets for anti-infectives and therapeutic approaches. The development of
      modulators of host responses and mediators of host damage will be facilitated by
      the research on interactions of microbes and hosts, including mechanisms of host
      damage, acute and chronic relationships as well as commensalisms. The study of
      multiple pathogenic and non-pathogenic microbes interacting in the host will
      improve the management of multiple infections and will allow probiotic and
      prebiotic interventions. Needless to iterate, the application of the results of
      improved prevention and treatment of infections into clinical tests will have a
      positive impact on the management of human and animal disease. The Pathogenomics
      Research Agenda draws on discussions with experts of the Network of Excellence
      "EuroPathoGenomics" at the management board meeting of the project held during 18
      21 April 2007, in the Villa Vigoni, Menaggio, Italy. Based on a proposed European
      Research Agenda in the field of pathogenomics by the ERA-NET PathoGenoMics the
      meeting's participants updated the established list of topics as the research
      agenda for the future.

PMID- 18321794
TI  - The electron transfer reactivity of kaempferol and its interaction with amino
      acid residues.
AB  - In this work, the electron transfer reactivity of kaempferol was studied and the
      interaction in vivo between kaempferol and protein was simulated.
      Dimethylsulfoxide (DMSO) as an aprotic solvent was employed to simulate the
      specific environment. Various residues of amino acids were used to study the
      effect of the amino acids in the active site of protein on the electron transfer
      reactivity of kaempferol. Experimental results revealed that the redox activity
      of kaempferol was different in aprotic medium DMSO from that in water, and a new
      redox process was further found. Of all the residues tested, nitrogenous
      nucleophile, for example, imidazole, was observed to be able to facilitate the
      electron transfer of kaempferol, and the mechanism was also proposed. This work
      might provide a simple model to study the electron transfer reactivity of some
      small active organic molecules, especially medicines, in specific environment,
      which might approach a more accurate understanding of the activity of some
      medicines in vivo.

PMID- 18321795
TI  - Mrc1, Tof1 and Csm3 inhibit CAG.CTG repeat instability by at least two
      mechanisms.
AB  - Trinucleotide repeats frequently expand and contract in humans and model
      organisms. Protein factors that modulate this process have been found by
      candidate gene approaches or mutant screens for increased expansion rates. To
      extend this effort, Saccharomyces cerevisiae mutants with higher CAG.CTG repeat
      contraction rates were sought using a disruption library. This screen identified
      Mrc1, the homolog of human Claspin, which mediates the replication and DNA damage
      checkpoints, and also couples the replicative helicase and polymerase. Genetic
      analysis showed that Mrc1, along with Tof1 and Csm3, inhibits instability in two
      distinct ways. Contraction rates of (CAG)(20) tracts are elevated by loss of
      Mrc1, Tof1 or Csm3, but not by defects in most replication checkpoint or DNA
      damage checkpoint proteins. The three proteins likely inhibit contractions
      primarily through their coupling activity, which would prevent accumulation of
      single-strand template DNA prior to the formation of aberrant secondary
      structure. In contrast, expansion rates of (CTG)(13) are elevated in strains
      defective for Mrc1, Tof1, Csm3, Mec1, Ddc2, Rad24, Ddc1, Mec3, Rad17, Rad9, Rad53
      or Chk1, suggesting that the DNA damage checkpoint inhibits expansions after
      formation of repeat-dependent structures. Together, these results indicate that
      at least two Mrc1-dependent mechanisms function to reduce CAG.CTG repeat
      instability.

PMID- 18321796
TI  - Budding yeast Mms22 and Mms1 regulate homologous recombination induced by
      replisome blockage.
AB  - Yeast cells lacking MMS22 or MMS1 are hypersensitive to agents that perturb
      replisome progression but the cellular functions of these genes are unknown. In
      this study we investigate the involvement of budding yeast MMS22 and MMS1 in
      homologous recombination (HR). Recombination between sister chromatids or between
      homologous chromosomes induced by agents that block replisomes was severely
      defective in cells lacking MMS22 or MMS1. In contrast, HR induced by double
      strand breaks was not affected by the absence of these genes. Major defects in
      MMS-induced HR were also observed in cells lacking the cullin RTT101, the histone
      acetyltransferase RTT109 and in cells lacking the histone chaperone ASF1, all of
      which interact genetically with MMS22 and MMS1. Finally, we show that cells
      lacking either MMS22 or MMS1 are defective in recovery from MMS-induced replisome
      stalling. These results identify Mms22 and Mms1 as S-phase specific recombination
      promoting factors.

PMID- 18321797
TI  - Development and validation of a stereoselective liquid chromatography-tandem mass
      spectrometry assay for quantification of S- and R-metoprolol in human plasma.
AB  - A stereoselective liquid chromatography-tandem mass spectrometry assay was
      developed and validated for quantification of S- and R-metoprolol at
      concentrations of 0.5-50 microg/L in human plasma. Metoprolol was extracted from
      plasma by liquid-liquid extraction with ethyl acetate (82% recovery).
      Chromatographic separation of the enantiomers was achieved on a chiral
      Chirobiotic T column using an isocratic mobile phase consisting of
      methanol/acetic acid/ammonia (100/0.15/0.15, v/v/v). An ion trap mass
      spectrometer with an electrospray interface was used for detection in the
      positive mode, monitoring the m/z transition 268-->191 for metoprolol. Standard
      curves for S- and R-metoprolol fitted quadratic functions (r(2)>or=0.9995) over
      the range 0.5-50 microg/L in plasma, with 0.5 microg/L representing the limit of
      quantification. In this range, relative standard deviations were <6% for intra
      day precision and <10% for inter-day precision. The accuracy was within the range
      of 92-105%.

PMID- 18321798
TI  - The use of molecular assays in the management of viral hepatitis.
AB  - Molecular assays are instrumental in the clinical management of viral hepatitis.
      During the past years, a wide variety of molecular assays have been developed and
      implemented. This considerably improved the understanding of the natural history
      and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis
      delta virus (HDV) hepatitis, but also caused uncertainties in the selection of
      the most appropriate assays for clinical requirements. Indeed, a rational choice
      and application of these assays requires adequate knowledge of the performance of
      the single test. Moreover, the choice of the most accurate assay for patients'
      needs and physicians' objectives, needs to be oriented to specific contexts, such
      as diagnosis, management or treatment. In the past, a hurdle in the routine use
      of assays for hepatitis viruses nucleic acid quantification was represented by
      the availability of only "home brew" methods which lacked standardization. Major
      improvement in addressing the use of molecular assays for viral hepatitis has
      been derived from recent standardization procedures that allowed a comparison
      between different tests after results were given as International Units. In
      addition, it should be reminded that, before getting into the market, molecular
      assays should be approved by European regulation authorities and validated using
      internationally recognized standards. A subsequent clinical validation should
      address the diagnostic accuracy of the assay. These proceedings have the aim of
      identifying which molecular tests, among those currently available, meet clinical
      requirements for each specific application.

PMID- 18321799
TI  - Morphology and electrochemical behavior of Ag-Cu nanoparticle-doped amalgams.
AB  - The aim of this study was to introduce Ag-Cu phase nanopowder as an additive to
      improve the corrosion behavior of dental amalgams. A novel Ag-Cu nanopowder was
      synthesized by the precipitation method. An amalgam alloy powder (World-Cap) was
      added and mixed with 5 wt.% and 10 wt.% of Ag-Cu nanopowders, respectively, to
      form experimental amalgam alloy powders. The original alloy powder was used as a
      control. Alloy powders were examined using X-ray diffraction, transmission
      electron microscopy (TEM), scanning electron microscopy and electron probe
      microanalysis. Amalgam disk specimens of metallurgically prepared were tested in
      0.9% NaCl solution using electrochemical methods. The changes in the corrosion
      potential and anodic polarization characteristics were determined. Corrosion
      potential data were analyzed statistically (n=3, analysis of variance, Tukey's
      test, p<0.05). The diameters of lamellar structure Ag-Cu nanoparticles were
      measured to be approximately 30 nm. The composition of the Ag-Cu nanoparticles
      determined by TEM-energy-dispersive spectroscopy was 56.28 at.% Ag-43.72 at.% Cu.
      A light-shaded phase was found mixing with dark Cu-Sn reaction particles in the
      reaction zones of Ag-Cu nanoparticle-doped amalgams. The Ag-Cu nanoparticle-doped
      amalgams exhibited zero current potentials more positive than the control
      (p<0.05) and no current peak was observed at -325mV that related to Ag-Hg phase
      and Cu6Sn5 phase in anodic polarization curves. The results indicated that the
      corrosion resistance of high-copper single-composition amalgam could be improved
      by Ag-Cu nanoparticle-doping.

PMID- 18321800
TI  - Characterization of the mechanical properties of tough biopolymer fibres from the
      mussel byssus of Aulacomya ater.
AB  - Byssus fibres are tough biopolymer fibres produced by mussels to attach
      themselves to rocks. In this communication, we present the mechanical properties
      of the byssus from the South American mussel Aulacomya ater which have not been
      previously reported in the literature. The mechanical properties of the whole
      threads were assessed by uniaxial tensile tests of dry and hydrated specimens.
      Elastoplastic and elastomeric stress-strain curves were found for byssal threads
      from A. ater in the dry and hydrated state, respectively. The results obtained
      from mechanical tests were modelled using linear, power-law-type and Mooney
      Rivlin relationships. These methods for dealing with tensile measurements of
      mussel byssus have the potential to be used with other stretchy biomaterials.

PMID- 18321801
TI  - Midline palate perforation secondary to cocaine abuse.

PMID- 18321802
TI  - Autologous fat grafting to the breast for cosmetic enhancement: experience in 66
      patients with long-term follow up.
AB  - BACKGROUND: Autologous fat grafting to the breast for cosmetic enhancement
      remains controversial because the efficacy and fate of fat grafting to the breast
      are primarily unknown. In this report, we present our retrospective study in 66
      patients who underwent autologous fat grafting to the breast for various cosmetic
      reasons and who were followed with sonography, mammography, or magnetic resonance
      imaging (MRI). METHODS: Sixty-six patients who desired cosmetic enhancement of
      the breast for various reasons underwent autologous fat transplantation between
      August 2000 and March 2005 in our institution. The cosmetic outcome was assessed
      by the plastic surgeons as well as the patients. The imaging features of fat
      necrosis, cyst formation, and calcification in these patients were carefully
      studied and biopsies of palpable lumps were evaluated histologically. RESULTS:
      All patients were followed from 13 to 61 months with an average of 37 months.
      Breast cosmetic contour was significantly improved in 28 patients (42.4%),
      improved in 24 patients (36.4%), and not improved in 14 patients (21.2%) as
      judged by the plastic surgeons. Twenty-seven patients (40.9%) were very
      satisfied, 26 patients (39.4%) were satisfied, and 13 patients (19.7%) were
      unsatisfied. Eleven patients (16.7%) developed liponecrotic cysts but only two
      patients elected to have the breast lump surgically removed. CONCLUSION:
      Autologous fat grafting to the breast can be a useful procedure for cosmetic
      enhancement in many patients who desire such a procedure. Patients with breast
      contour deformities after removal of silicon implants were found to be the best
      candidates for fat grafting. The primary long-term complication is the formation
      of liponecrotic cysts which have characteristically benign appearances in
      sonography, mammography or MRI.

PMID- 18321803
TI  - Ubc9 promotes the stability of Smad4 and the nuclear accumulation of Smad1 in
      osteoblast-like Saos-2 cells.
AB  - Bone morphogenetic proteins (BMPs) play important roles in osteoblast
      differentiation and maturation. In mammals, the BMP-induced receptor-regulated
      Smads form complexes with Smad4. These complexes translocate and accumulate
      within the nucleus, where they regulate the transcription of various target
      genes. However, the function of Smad4 remains unclear. We performed a yeast two
      hybrid screen using Smad4 as bait and a cDNA library derived from human bone
      marrow to identify the proteins interacting with Smad4. Two full-length cDNA
      clones for Ubc9 were identified, and the potential functions of Ubc9 were
      investigated. To determine the role of Ubc9 in the BMP signaling pathway, the
      endogenous transcription of Ubc9 in the human osteoblast cell line Saos-2 was
      silenced using siRNA. The expression of BMP-induced transcription factors,
      including Runx2, Dlx5, Msx2, and Osterix, was examined using real-time reverse
      transcription polymerase chain reaction (qRT-PCR), and the protein expression of
      Smad4, Smad1, phosphorylated Smad1, and BMP type I receptors was determined by
      Western blotting. The subcellular localization of Smad1 and Smad4 was observed
      using immunofluorescence staining after Ubc9 silencing. To determine whether
      Smad4 is sumoylated in vitro, recombinant Smad4 was purified and sumoylated Smad4
      was visualized using Western blotting. The mRNA expression of various
      transcription factors was markedly inhibited after Ubc9 silencing. The protein
      levels of Smad4 and phosphorylated Smad1 decreased in a dose-dependent manner
      according to the amount of siRNA applied. Gene silencing also decreased the
      nuclear accumulation of Smad1 and Smad4. The sumoylation assay showed that
      sumoylated Smad4 is present and dependent on Ubc9 in vitro, which was confirmed
      by pretreatment with Senp2, a SUMO-protease. These results suggest that Ubc9
      promotes the stability of sumoylated Smad4. Furthermore, the expression of key
      transcription factors, phosphorylated Smad1 protein, and the nuclear accumulation
      of Smad1 and Smad4 are inhibited by Ubc9 silencing. Thus, Ubc9 plays an important
      role in the up-regulation of the BMP signaling pathway.

PMID- 18321804
TI  - Retrospective study assessing efficacy of treatment of large colonic impactions.
AB  - Cases with a history of colic due to a large colonic impaction were recruited
      retrospectively to assess the treatment efficacy and complications of oral and
      parenteral fluid therapy regimes for correction of primary large colon
      impactions. Oral isotonic fluids had been administered at varying intervals
      following initial treatment with magnesium sulphate and water. There was no
      significant difference in complication rates between groups. Considering
      complication rates with impaction clearance, hourly administration of oral fluids
      appears to be the most appropriate treatment regime of those investigated.

PMID- 18321805
TI  - Determination of the source of increased serotonin (5-HT) concentrations in blood
      and peritoneal fluid of colic horses with compromised bowel.
AB  - REASONS FOR PERFORMING STUDY: Increased plasma (5-HT) concentrations are reported
      in horses predisposed to develop laminitis and after i.v. infusion of endotoxins.
      In the equine jejunum contractile 5-HT1A-like receptors show tachyphylaxia upon
      prolonged activation with 5-HT. Therefore, increased systemic 5-HT release in
      colic horses could play a possible role in the pathophysiology of ileus.
      OBJECTIVE: To investigate possible increased systemic release of 5-HT in colic
      horses with compromised bowel and to identify the source of 5-HT overload.
      METHODS: Concentrations of 5-HT were determined in plasma and peritoneal fluid
      (PF) of healthy horses (n = 10), strangulating small intestinal colic horses (n =
      18), nonsurgical colic horses (n = 10) and cryptorchid stallions (n = 6). It was
      attempted to identify the source of 5-HT overload by comparing the blood and PF 5
      HT concentrations within horses and by assessing the in vivo platelet activation
      through determination of the beta-thromboglobulin (beta-TG)/platelet factor 4
      (PF4) ratio. RESULTS: All horses in the strangulating small intestinal colic
      group had plasma (P = 0.006) and PF (P = 0.01) 5-HT concentrations above those
      found in the control group. Plasma beta-TG/PF4 ratio in these horses exceeded 2
      in all cases, indicating in vivo platelet activation. Concentrations of 5-HT in
      PF of colic horses with compromised bowel were significantly lower than the
      corresponding plasma concentrations (P = 0.005). POTENTIAL RELEVANCE: In horses
      with compromised bowel, significant amounts of 5-HT can be released into the
      systemic circulation, through massive release of platelet-stored 5-HT. 5-HT is a
      very potent proinflammatory, vasoconstrictive and immunomodulatory agent. In view
      of the rapid and prolonged tachyphylaxia, shown for the jejunal 5-HT1A-like
      receptors, this increased systemic 5-HT release could play a role in the
      pathophysiology of ileus in horses.

PMID- 18321806
TI  - The creation of an international audit and database of equine colic surgery:
      survey of attitudes of surgeons.
AB  - REASONS FOR PERFORMING STUDY: Currently, there is a lack of available evidence
      based data concerning the optimum treatments for horses affected by different
      types of colic and this precludes the application of clinical audit in this area.
      In order to accumulate such data, a large-scale, multicentre database of the
      outcomes of colic surgery is proposed. The attitudes of surgeons is an important
      consideration in determining the feasibility of developing this database.
      OBJECTIVES: To assess attitudes and opinions of equine surgeons concerning
      clinical audit and to assess the perceived advantages and problems of setting up
      a large-scale international audit/database of colic surgery. METHODS: Interviews
      were conducted with 30 equine surgeons (large animal/equine surgeons who are
      diplomates of either the American College of Veterinary Surgeons or the European
      College of Veterinary Surgeons). Questionnaires were sent by e-mail to 98 equine
      surgeons. RESULTS: Face to face interviews were conducted (n = 30) and 43/98
      completed questionnaires received (44%). The results of the 2 techniques were
      very similar. There was generally a high level of interest in the development of
      a large scale database of colic surgery, but perceived problems included time to
      collect and submit data, and confidentiality issues. A minority of surgeons
      reported that they were undertaking any form of specific monitoring of the
      results of colic surgery within their hospitals. CONCLUSIONS: There is a good
      level of interest among equine surgeons to develop a large scale database of
      colic surgery and most would be willing to contribute data from their own
      hospitals provided that data collection is quick and easy, and that
      confidentiality is maintained.

PMID- 18321807
TI  - The pathology of bronchointerstitial pneumonia in young foals associated with the
      first outbreak of equine influenza in Australia.
AB  - REASONS FOR PERFORMING STUDY: The first outbreak of equine influenza virus (EIV)
      infection was confirmed in Australia in 2007. Some EIV-positive young foals died
      with bronchointerstitial pneumonia, an rare disease process in this age group
      that is often postulated to be caused by viral infection. OBJECTIVES: The aim of
      this study was to describe post mortem lesions in EIV-infected foals. METHODS:
      Post mortem examinations were conducted on 11 young foals (age 2-12 days)
      submitted to the Scone Veterinary Hospital, NSW over a 2-month period in 2007.
      The foals had presented with or developed fatal pneumonia, and were known or
      suspected to be EIV-positive. Equine influenza virus nucleic acid was detected in
      tissue specimens using an Influenza A group reactive real-time reverse
      transcriptase PCR assay. RESULTS: Grossly there was diffuse or extensive
      pulmonary consolidation. Histological changes included: bronchiolar and alveolar
      necrosis; neutrophilic infiltration; hyaline membrane formation; and hyperplasia
      and squamous metaplasia of airway epithelium. Tissues for 10 foals were EIV
      positive, with a positive nasal swab from the remaining animal. CONCLUSIONS: This
      is the first detailed pathological description of bronchointerstitial pneumonia
      associated with EIV infection in young foals. It is also the first series of such
      cases in which a causative agent has consistently been detected. POTENTIAL
      RELEVANCE: Given the findings in this outbreak, and a previous outbreak in the UK
      in 1965 involving a similarly naive population, veterinary clinicians and
      pathologists should be aware that EIV can cause fatal bronchointerstitial
      pneumonia in young foals that do not have maternal immunity. The lesions did not
      differ from those previously reported in foals of various ages with
      bronchointerstitial pneumonia of other or undefined causes, indicating that this
      is most likely a stereotypical response to a variety of insults. Therefore,
      tissue specimens should be obtained from cases of pneumonia in young foals for
      virological and bacteriological testing.

PMID- 18321808
TI  - Mechanical nociceptive thresholds within the pastern region of Tennessee Walking
      Horses.
AB  - REASONS FOR PERFORMING STUDY: 'Soring' is the term used to describe the
      application of an irritant to the distal forelimbs of gaited horses with the sole
      intent of inflicting pain and inducing altered gait, illegally practiced in
      Tennessee Walking Horses. Objective methods for the detection of limb pain due to
      this practice are, however, lacking. OBJECTIVES: To assess whether Tennessee
      Walking Horses respond to manual pressures<or=10 kg/cm2 and to establish
      reference mechanical nociceptive thresholds (MNTs) within the pastern region.
      METHODS: In 25 mature Tennessee Walking Horses in which no irritant had been
      applied, MNTs were evoked by a pressure algometer at 4 sites within the pastern
      region of each thoracic limb by 6 different examiners. The effects of age, sex,
      weight, height at withers, exercise and hand dominance of the examiners on MNTs
      were assessed. Correlations between the horse's perceived mental status,
      tolerance to the procedure and MNT values were also evaluated. RESULTS:
      Mechanical nociceptive thresholds<or=10 kg/cm2 were observed in 20% of
      measurements, of which the mean+/-s.d. MNT was 9.5+/-0.3 kg/cm2. Within 4 pastern
      sites, the palmar region had the lowest reference MNT value of 19.5+/-3.6 kg/cm2.
      Subject status, exercise, hand dominance, horse mental status and horse procedure
      tolerance did not significantly affect MNT values. CONCLUSIONS: Reference MNTs of
      the pastern region of nontreated Tennessee Walking Horses provide an objective
      standard for the evaluation of those potentially applied irritant. POTENTIAL
      RELEVANCE: Pressure algometry, in lieu of digital pressure, can quantify
      mechanical pressure applied during inspections to detect irritant therapy and
      provide consistency between examiners.

PMID- 18321809
TI  - In vitro effects of hydrochloric and lactic acids on bioelectric properties of
      equine gastric squamous mucosa.
AB  - REASONS FOR PERFORMING STUDY: Volatile fatty acids, byproducts of carbohydrate
      fermentation by resident bacteria, have been implicated in causing nonglandular
      (NG) gastric ulcers. Lactic acid (LA), also produced by stomach bacteria, may
      cause gastric ulcers when exposed to the equine NG mucosa. OBJECTIVES: To
      investigate the in vitro effects of LA on equine NG mucosa bioelectric
      properties, sodium transport and tissue resistance. METHODS: Gastric tissues
      obtained from 13 mature horses were studied in Ussing chambers. Short-circuit
      current (Isc) and potential difference (PD) were measured, and electrical
      resistance (R) and conductance (G) calculated for tissues after addition of HCl
      and LA (5, 10, 20 and 40 mmol/l) in normal Ringer's solution (NRS). RESULTS:
      Mucosa exposed to HCl or LA (5, 10 and 20 mmol/l) in NRS (pH 1.5 and to a lesser
      extent pH 4.0) had a significant decrease in Isc and PD. Mucosa exposed to a high
      concentration of LA (40 mmol/l) in NRS (LRS) at pH 1.5 showed an increased G, but
      this increase was not significant. Values returned to baseline after solutions
      were returned to pH 7.0. Histological changes were consistent with HCl-induced
      (pH <4.0) acid damage. CONCLUSIONS: HCl induced alteration in bioelectric
      properties of equine NG mucosa whereas addition of LRS did not, other than those
      changes seen with HCl alone.

PMID- 18321810
TI  - Surgical treatment of colic in the miniature horse: a retrospective study of 57
      cases (1993-2006).
AB  - REASONS FOR PERFORMING STUDY: It has been suggested that the rate of post
      operative abdominal adhesions in miniature horses is higher than that for other
      breeds. However, few reports exist in the veterinary literature describing
      complications and long-term survival following surgical treatment of colic in
      these horses. OBJECTIVES: To determine the prevalence of surgical lesions in
      miniature horses with acute abdominal disease in terms of clinical signs,
      surgical management, post operative treatment and complications, as well as short
      and long-term survival. METHODS: Medical records of 57 American Miniature Horses
      undergoing surgical treatment for acute abdominal pain at the Michigan State
      University Large Animal Veterinary Teaching Hospital 1993-2006 were evaluated for
      clinical information. Owners and trainers were contacted to gain information
      regarding long-term survival. RESULTS: The most common surgical lesion was a
      faecalith (38/57 cases) located primarily within the descending colon and most
      frequently diagnosed in horses age <6 months (19/38 cases). Short-term survival
      to hospital discharge for horses recovered from anaesthesia was 98% (55/56) with
      the most common post operative complications being diarrhoea and inappetance.
      Intra-abdominal adhesions were identified in 2/8 horses requiring a second
      celiotomy. Long-term follow-up was available for 45 horses and 87% (39/45) were
      alive at least 12 months after surgery. CONCLUSIONS: As previously reported,
      faecalith obstruction is a frequent surgical lesion in the miniature horse and is
      most common in miniature horses age <6 months. The incidence of adhesion
      formation may be lower than previously reported.

PMID- 18321811
TI  - Large colon resection and anastomosis in horses: 52 cases (1996-2006).
AB  - REASONS FOR PERFORMING STUDY: Large colon resection and anastomosis (LCRA) is the
      most aggressive method of surgical management of a colon with questionable
      viability. Currently, published studies are comprised mostly of broodmares and
      discuss short-term survival. OBJECTIVES: To determine the prognosis for survival
      after LCRA in a diverse population of horses, report the incidence of post
      operative complications, and determine if associations between analysed variables
      and survival rate exist. METHODS: The medical records of 52 horses that underwent
      LCRA were evaluated. Data were used to identify univariable associations with
      survival as well as complications related to LCRA. Chi-square, odds ratio with
      95% confidence interval, Mann-Whitney or Kruskal-Wallis tests were used, with
      significance set at P<0.05. RESULTS: Forty-four horses (84.6%) survived
      anaesthesia and recovery, 30 (57.7%) survived to be discharged from the hospital.
      Of the variables analysed, heart rate 24 h after recovery was significantly
      associated with mortality, as were endotoxaemia, ileus and peritonitis
      experienced post operatively. CONCLUSIONS: Heart rate 24 h after recovery may be
      a more reliable prognostic indicator than other analysed variables. Survival rate
      and complications after LCRA were similar to those previously reported.

PMID- 18321812
TI  - Attenuation of ischaemic injury in the equine jejunum by administration of
      systemic lidocaine.
AB  - REASONS FOR PERFORMING STUDY: Absorption of endotoxin across ischaemic-injured
      mucosa is a major cause of mortality after colic surgery. Recent studies have
      shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been
      used to treat post operative ileus, but it also has novel anti-inflammatory
      effects that could improve mucosal recovery after ischaemic injury. HYPOTHESIS:
      Systemic lidocaine ameliorates the deleterious negative effects of flunixin
      meglumine on recovery of mucosal barrier function. METHODS: Horses were treated
      i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt,
      flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose
      followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine
      and lidocaine, with 6 horses allocated randomly to each group. Two sections of
      jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local
      blood supply, via a midline celiotomy. Horses were monitored with a behavioural
      pain score and were subjected to euthanasia 18 h after reversal of ischaemia.
      Ischaemic-injured and control jejunum was mounted in Ussing chambers for
      measurement of transepithelial electrical resistance (TER) and permeability to
      lipopolysaccharide (LPS). RESULTS: In ischaemic-injured jejunum TER was
      significantly higher in horses treated with saline, lidocaine or lidocaine and
      flunixin meglumine combined, compared to horses treated with flunixin meglumine.
      In ischaemic-injured jejunum LPS permeability was significantly increased in
      horses treated with flunixin meglumine alone. Behavioural pain scores did not
      increase significantly after surgery in horses treated with flunixin meglumine.
      CONCLUSIONS: Treatment with systemic lidocaine ameliorated the inhibitory effects
      of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury,
      when the 2 treatments were combined. The mechanism of lidocaine in improving
      mucosal repair has not yet been elucidated.

PMID- 18321813
TI  - Towards an optimal treatment strategy for patients with oesophageal cancer.

PMID- 18321814
TI  - The era of stem cells.

PMID- 18321815
TI  - Uveal vs. cutaneous melanoma. Origins and causes of the differences.
AB  - Melanoma is a malignant tumour derived from melanocytes (dendritic cells
      originated from the neural crest and capable to produce melanin synthesis) that
      could be established on the skin or less frequently on the uvea. The cellular
      origin from both kind of melanoma seems to be the same but the melanocytes
      migrates to the epithelia for cutaneous melanoma, while for uveal melanoma, they
      migrate to mesodermic tissues. Despite the common origin, both melanomas show
      extreme differences in their metastatic potential, clinical response to
      treatments, immune response and genetic alterations. We will describe some of
      those differences in this review.

PMID- 18321816
TI  - The role of the NFkappaB signalling pathway in cancer.
AB  - The nuclear factor kappa B (NFkappaB) signalling pathway regulates the expression
      of hundreds of genes that are involved in different cellular processes such as
      cell proliferation, survival, stress responses, cellular immunity and
      inflammation. Its aberrant regulation is involved in several pathologies, but its
      relevance in cellular transformation and cancer development has been extensively
      studied. Mutations in the core components of NFkappaB as well as in the cellular
      machinery that regulates its activation have been found in many types of tumours.
      On the other hand, its role in promoting cell survival is an important obstacle
      in many cancer therapies. The development of chemical inhibitors that block
      NFkappaB activation acting either directly on IKKs or on the proteosome machinery
      has shown antitumour and proapoptotic activity both in preclinical and clinical
      studies.

PMID- 18321817
TI  - Photodynamic therapy of cancer. Basic principles and applications.
AB  - Photodynamic therapy (PDT) is a minimally invasive therapeutic modality approved
      for clinical treatment of several types of cancer and non-oncological disorders.
      In PDT, a compound with photosensitising properties (photosensitiser, PS) is
      selectively accumulated in malignant tissues. The subsequent activation of the PS
      by visible light, preferentially in the red region of the visible spectrum
      (lambda>or=600 nm), where tissues are more permeable to light, generates reactive
      oxygen species, mainly singlet oxygen ((1)O(2)), responsible for cytotoxicity of
      neoplastic cells and tumour regression. There are three main mechanisms described
      by which (1)O(2) contributes to the destruction of tumours by PDT: direct
      cellular damage, vascular shutdown and activation of immune response against
      tumour cells. The advantages of PDT over other conventional cancer treatments are
      its low systemic toxicity and its ability to selectively destroy tumours
      accessible to light. Therefore, PDT is being used for the treatment of
      endoscopically accessible tumours such as lung, bladder, gastrointestinal and
      gynaecological neoplasms, and also in dermatology for the treatment of non
      melanoma skin cancers (basal cell carcinoma) and precancerous diseases (actinic
      keratosis). Photofrin, ALA and its ester derivatives are the main compounds used
      in clinical trials, though newer and more efficient PSs are being evaluated
      nowadays.

PMID- 18321818
TI  - Conservative management of patients with early endometrial carcinoma: a
      systematic review.
AB  - OBJECTIVE: To know the characteristics of endometrial adenocarcinoma in young
      patients and to review the published experience in patients with endometrial
      adenocarcinoma that were conservatively managed with hormonal therapy to spare
      their fertility. METHODS: We carried out a search in the Survey conducted by the
      Section of Oncologic Gynecology of SEGO (Spanish Society of Gynecologists) to
      identify the characteristics of young patients with endometrial adenocarcinoma.
      In addition we searched MEDLINE and other databases for English-language articles
      describing patients with endometrial adenocarcinoma who were treated with
      hormonal therapy. The search included articles published between January 1966 and
      January 2007. RESULTS: Endometrial carcinoma in patients under 45 years old is an
      unusual condition that shows a more favourable pattern than in older patients.
      One hundred and thirty-three patients were found in the search. The average
      duration of hormonal therapy was approximately six months. The average response
      time was 12 weeks; 76% of patients treated with hormonal therapy had a complete
      response and the other 24% never responded to treatment. Of those who initially
      responded, 66% percent did not show recurrence of disease. The other 34% had a
      relapse. There have been 4 published deaths of conservatively managed patients.
      CONCLUSION: A conservative approach in these patients can offer reasonable
      oncological security and the opportunity of fulfilling their maternal desires in
      selected cases. However, consideration should be taken regarding the potential
      adverse outcomes that have been recently published in the literature.

PMID- 18321819
TI  - Superoxidase dismutase (SOD) topical use in oncologic patients: treatment of
      acute cutaneous toxicity secondary to radiotherapy.
AB  - OBJECTIVE: The objective of this study is to evaluate the efficiency of SOD
      applied topically in oncologic patients affected by acute radiodermatitis.
      MATERIALS AND METHOD: This study includes 57 patients who showed a dermatitis
      grade 2 or superior; they were administered SOD ointment b.i.d. (40 mg, weekly)
      and follow-up continued for 12 weeks. RESULTS: At the end of radiotherapy, 77.1%
      of the patients ameliorated completely or partially, and at the end of the 12
      week period 100% of patients were free of toxicity. No acute toxicity relapses
      were reported. Response time reduced during radiotherapy, as well as the
      treatment time at the end of it. CONCLUSIONS: The employment of SOD topically is
      efficient in the treatment of radiodermatitis, which is an acute side effect of
      radiotherapy.

PMID- 18321820
TI  - Acoustic voice analysis in different phonetic contexts after larynx radiotherapy
      for T1 vocal cord carcinoma.
AB  - INTRODUCTION: Radiotherapy for early vocal cord carcinoma affects quality of
      voice. Nevertheless, most patients refer to having a high satisfaction level with
      their voice. The few acoustic studies on quality of voice have been performed
      only in prolonged vowel production, which is not a usual speech situation. The
      present study has been done with the aim of establishing which phonetic
      situations reflect a greater alteration in voice production related to
      irradiation. MATERIAL AND METHODS: Eighteen male patients irradiated for Tis-T1
      vocal cord carcinoma and a control group of 31 non-irradiated subjects were
      included in a study of acoustic voice analysis. This analysis was performed one
      year after radiotherapy. Patients and control group voices were tape recorded in
      extended vowel production, oral reading of a standard paragraph, spontaneous
      speech and in a song. Acoustic analysis was performed by a Kay Elemetric's
      Computerized Speech Lab (model CSL #4300). Fundamental frequency, jitter, shimmer
      and harmonics-to-noise ratio were obtained in both groups. Statistical test: Lin
      concordance coefficient and Pearson's correlation coefficient, Student's t-test
      and ROC curves. RESULTS: Concordance and correlation studies did not allow
      selection of any subgroup in acoustic parameters and different acoustic
      situations. Acoustic parameters had higher median values in irradiated patients.
      Student's t-test showed significant differences for fundamental frequency in
      sustained vowel production and spontaneous speech; for jitter there was
      statistical significance in all the acoustic situations and for shimmer in oral
      reading and song. Jitter showed a cut-off of 2.02% with a sensitivity of 89% and
      specificity of 97% in classifying irradiated and non-irradiated groups. The ROC
      curve for jitter correctly classified 94% of subjects into irradiated or non
      irradiated groups. CONCLUSIONS: The present study showed that jitter obtained
      from spontaneous speech was the most relevant parameter in discriminating voice
      in irradiated patients by acoustic analysis. Jitter in spontaneous speech is in
      need of more analysis in bigger series and in more advanced stages of larynx
      cancer as its relevance has been demonstrated.

PMID- 18321821
TI  - The clinical significance of lymph node micrometastasis in stage I and stage II
      colorectal cancer.
AB  - AIM: Recent advances in immunohistochemical techniques have made it possible to
      identify micrometastasis using antibodies to cytokeratins (CK). The aim of the
      study was to determine the prevalence and prognostic significance of
      immunohistochemically detected micrometastasis (IHM) in patients with localised
      colorectal cancer (CRC) (Dukes' A and B). A further aim was to study the
      prognostic role of histopathological factors such as vascular invasion. METHODS:
      The original histology of 168 consecutive patients with Dukes' A or B tumours who
      had undergone curative resection was reviewed. Immunohistochemical staining was
      performed using CK antibodies, AE1/AE3 and MNF116 on all (n=898) lymph nodes.
      Survival analysis was performed on 105 cases that had been followed up until
      death or for at least 5 years. RESULTS: IHM were detected in 17.3% of lymph nodes
      analysed. Adverse outcome (death/local recurrence) was recorded in 8/49 (16%)
      patients with IHD-positive nodes and in 10/56 (18%) patients negative for IHM.
      IHM was not associated with adverse outcome on either univariate (p=0.540) or
      multivariate analyses (p=0.673). There was no correlation of IHM with age,
      gender, site, size and grade of tumour, depth of tumour invasion or perineural
      and vascular invasion. Vascular invasion was the only independent prognostic
      factor identified. DISCUSSION: We have shown that isolated CK-positive
      epithelioid cells are commonly found in morphologically benign pericolic lymph
      nodes of patients with localised (Dukes' A or B) CRC. These cells may represent
      occult micrometastasis but are not clinically significant. Vascular invasion
      identifies patients with localised CRC likely to develop recurrences or die of
      disease.

PMID- 18321822
TI  - Meningeal relapse by follicular lymphoma as a single mass.
AB  - Follicular lymphoma is the second most common lymphoma throughout the world. Its
      course is usually indolent. Affection of Central Nervous System by a follicular
      lymphoma is usually as primary disease, and secondary affection is usually due to
      high-grade transformation. In this case-report we describe a young patient who
      presented a follicular lymphoma which secondary affected the central nervous
      system without high grade transformation.

PMID- 18321823
TI  - First-line treatment of advanced gastric cancer and hepatic dysfunction with
      oxaliplatin, 5-fluorouracil and cetuximab.
AB  - There is no standard chemotherapy regimen in advanced gastric cancer with poor
      performance status and hepatic dysfunction. New chemotherapeutical agents and
      targeted therapy have demonstrated promising results in terms of efficacy and
      safety in phase II clinical trials. We report the case of a 68-year-old man with
      stage IV gastric cancer and severe hepatic dysfunction due to liver metastases
      treated with a combination of oxaliplatin, 5-fluorouracil and cetuximab.

PMID- 18321825
TI  - Both sides now.

PMID- 18321824
TI  - Preventing second cancers in cancer survivors.
AB  - PURPOSE/OBJECTIVES: To provide a systematic review of the secondary prevention
      practices of cancer survivors guided by the Interaction Model of Client Health
      Behavior. DATA SOURCES: Articles published in peer-reviewed journals from 1996
      2007. DATA SYNTHESIS: Despite their increased risk for second cancers, few cancer
      survivors maintain regular follow-up with a clinician knowledgeable of late
      effects. Cancer screening rates for cancer survivors are below optimal levels
      recommended for the general population. Multiple antecedents explain survivors'
      health practices. Few tested interventions are available to promote secondary
      prevention practices among cancer survivors. CONCLUSIONS: Cancer survivors are
      less likely to adopt secondary prevention practices than individuals without a
      cancer history. IMPLICATIONS FOR NURSING: Nurses can encourage cancer survivors
      to adopt secondary prevention practices by providing positive reinforcement,
      support, and education. As more comprehensive, evidence-based guidelines for
      longitudinal care become available, nurses will be able to provide care to
      survivors with greater confidence and certainty.

PMID- 18321826
TI  - The Oncology Nursing Society, ONS Foundation, and Oncology Nursing Certification
      Corporation Commercial Support Position.

PMID- 18321828
TI  - Fighting the flu: a vaccination program for healthcare workers.

PMID- 18321829
TI  - Care of patients with autism spectrum disorder undergoing surgery for cancer.

PMID- 18321830
TI  - Recovery after transverse rectus abdominis myocutaneous flap breast
      reconstruction surgery.
AB  - PURPOSE/OBJECTIVES: To assess pain and activity limitations and to determine
      realistic goals for recovery after a transverse rectus abdominis myocutaneous
      (TRAM) flap breast reconstruction in a standard rehabilitation and recovery
      program. Assessing patient satisfaction with educational information is a
      secondary objective. DESIGN: Before and after comparison. SETTING: A National
      Cancer Institute--designated comprehensive cancer center in the mid-Atlantic
      United States. SAMPLE: 16 women who had TRAM flap breast reconstruction. METHODS:
      Data were collected before surgery and four and eight weeks after surgery using
      an adapted Brief Pain Inventory, a recovery and rehabilitation assessment, and an
      evaluation of patient satisfaction. MAIN RESEARCH VARIABLES: Presence of pain;
      disruption of activities, relationships, and mood because of pain; pain relief
      measures; active range of motion; muscle strength; and satisfaction with
      educational information. FINDINGS: Pain and activity limitation scores were
      elevated four weeks after surgery and returned almost to baseline at eight weeks.
      Abdominal pain was significantly higher for women with free versus pedicled TRAM
      flap surgery, and women with previous back pain reported more lower back pain
      after surgery. Opioids, followed by nonsteroidal antiinflammatory drugs, were the
      most common pain relief method. Active range of motion and muscle strength showed
      no significant limitations at eight weeks. Patients were very satisfied with the
      educational information provided by nurses and physical therapists. CONCLUSIONS:
      Women can expect to have some pain and activity limitations four weeks after
      surgery but will be almost fully recovered at eight weeks. Educational
      information on pain management and resuming an active lifestyle were useful.
      IMPLICATIONS FOR NURSING: Nurses and physical therapists can positively influence
      recovery from TRAM flap breast reconstruction by educating patients.

PMID- 18321831
TI  - Self-reported cancer screening rates versus medical record documentation:
      incongruence, specificity, and sensitivity for African American women.
AB  - PURPOSE/OBJECTIVES: To evaluate levels of incongruence, specificity, and
      sensitivity between self-reported screening and medical record documentation for
      breast, cervical, and colorectal cancer screening. DESIGN: Descriptive,
      quantitative. SETTING: Federally qualified health centers in the southeastern
      United States. SAMPLE: 116 African American women. The mean age was 35 years, and
      the mean educational level was 12.6 years. METHODS: Women were eligible to
      participate in the study if they were older than age 18 and able to understand
      English or Spanish. They were recruited from the waiting areas of health centers
      over a consecutive five-day period. MAIN RESEARCH VARIABLES: Self-reported rates
      of screening and screening rates documented in the medical record. FINDINGS: The
      level of incongruence between self-report and medical record documentation was
      more than 50% for some procedures. Rates of specificity were high, particularly
      over time. Rates of sensitivity were 33% or less. CONCLUSIONS: The women tended
      to overreport screenings in the past year when compared to medical records. The
      women and medical records indicated that the screenings had not been performed in
      the past two to five years or more than five years ago. IMPLICATIONS FOR NURSING:
      Nurses are in a unique position to educate women about cancer screening in a
      culturally and educationally appropriate way while ensuring that those
      conversations and procedures are documented in the medical record by all
      providers.

PMID- 18321832
TI  - The breast cancer treatment response inventory: development, psychometric
      testing, and refinement for use in practice.
AB  - PURPOSE/OBJECTIVES: To describe the development, testing, and utility of the
      Breast Cancer Treatment Response Inventory (BCTRI), an instrument that captures
      the symptom experience of women with breast cancer. DATA SOURCES: Journal
      articles and results of research studies used to establish BCTRI psychometric
      properties. DATA SYNTHESIS: The tool is a valid and reliable method to determine
      and monitor numbers of symptoms, the severity of those symptoms, and the amount
      of distress experienced by patients. It is an easily and quickly employed
      assessment tool to guide and evaluate interventions. CONCLUSIONS: The BCTRI has
      strong psychometric properties and is a valid and reliable instrument to measure
      symptom experience among populations of breast cancer survivors. IMPLICATIONS FOR
      NURSING: Data collected using the BCTRI provide information that healthcare
      providers can use to target interventions toward symptoms that are most
      troublesome or distressful. The BCTRI can be used at meaningful points in
      treatment, recovery, and ongoing survivorship to explore the emerging concept of
      symptom experience in samples that reflect socioeconomically and ethnically
      diverse populations.

PMID- 18321833
TI  - Stress in patients with lung cancer: a human response to illness.
AB  - PURPOSE/OBJECTIVES: To provide a comprehensive overview of stress in patients
      diagnosed with lung cancer within the context of the four perspectives (normal
      physiologic, pathophysiologic, behavioral, and experiential) of the Human
      Response to Illness Model. DATA SOURCES: Published research articles, clinical
      articles, book chapters, and Internet sources on stress and lung cancer. Initial
      literature searches in CINAHL(R) and PubMed(R) focused on data subsequent to
      2001; classic research dating back to the 1970s also was included. DATA
      SYNTHESIS: Patients diagnosed with lung cancer experience psychological and
      biologic stressors from a delayed cancer diagnosis, symptom management issues,
      and social stigmatization of their illness. These stressors may cause a
      physiologic stress response, exacerbate the disease process, and decrease the
      patient's quality of life. CONCLUSIONS: Acknowledging that the stress response
      may interact with pathophysiologic disease processes such as lung cancer is
      important, and stress management in patients with cancer should include all four
      perspectives of the Human Response to Illness Model. IMPLICATIONS FOR NURSING: By
      examining the four perspectives, interventions may be implemented to prevent or
      alleviate the detrimental effects of the pathophysiologic stress response. This
      article establishes the relevance of this nursing model to assess and manage
      stress among patients with lung cancer and other types of cancers.

PMID- 18321834
TI  - Animal-assisted activity among patients with cancer: effects on mood, fatigue,
      self-perceived health, and sense of coherence.
AB  - PURPOSE/OBJECTIVES: To identify to what extent an animal-assisted activity (i.e.,
      visits with a dog) affects the mood, self-perceived health, and sense of
      coherence among patients undergoing radiation therapy. DESIGN: Pretest/post-test
      between and within groups. SETTING: Radiation oncology units of two hospitals in
      a mid-sized, midwestern city. SAMPLE: 30 adult patients undergoing nonpalliative
      radiation therapy. METHODS: After giving informed consent, participants were
      randomly assigned to receive 12 dog visits, 12 human visits, or 12 quiet reading
      sessions over a four-week period. FINDINGS: No statistically significant
      differences were found; however, compared with others their age, patients
      receiving dog visits viewed their health as improved over the four-week period.
      Participants described each of the three activities as beneficial. The study is
      primarily useful as a basis for planning additional research. CONCLUSIONS: The
      study warrants replication with a larger sample to determine applicability of
      animal-assisted activity in patients with cancer who are undergoing radiation
      therapy. IMPLICATIONS FOR NURSING: Patients may want and express benefit from
      animal-assisted activity dog visits, but the outcomes of the visits may not be
      measureable. Nurses should assess to what extent patients believe that such
      visits are beneficial by asking them. The visits may be valued by patients as
      helping to relieve their anxiety and as distractions from their disease and
      therapy.

PMID- 18321835
TI  - Nurse coaching to explore and modify patient attitudinal barriers interfering
      with effective cancer pain management.
AB  - PURPOSE/OBJECTIVES: To describe a complex coaching intervention to help patients
      with cancer pain explore beliefs and attitudinal barriers interfering with pain
      management. Patients were coached to explore beliefs about pain, communications
      about pain management, and the use of analgesics and nonpharmacologic
      interventions. DATA SOURCES: Published journal articles, abstracts, and
      psychology textbooks. DATA SYNTHESIS: Personal beliefs, related attitudinal
      barriers, and associated behaviors impede patient adherence to and success with
      pain management treatments. Interventions targeting beliefs help patients
      overcome attitudinal barriers, improve treatment adherence, and obtain better
      pain relief. CONCLUSIONS: Coaching patients to explore beliefs reduces
      ineffective behaviors and improves pain treatment adherence. IMPLICATIONS FOR
      NURSING: A coaching intervention incorporating assessment of patient beliefs
      promotes self-management, self-efficacy, and adherence to pain management
      treatment plans. Advanced practice nurses should consider incorporating this
      intervention into their communications with patients experiencing cancer pain.

PMID- 18321836
TI  - The nature of suffering and the goals of nursing.
AB  - PURPOSE/OBJECTIVES: To describe the nature of suffering and the goals of nursing.
      DATA SOURCES: Data sources informing this work included descriptions of suffering
      as derived from the literature; narrative data from patients, family caregivers,
      and nurses; and personal and professional experiences of the authors. DATA
      SYNTHESIS: Previous descriptions of suffering from seminal sources are
      insufficient to elucidate suffering from a nursing perspective. This article is
      parallel to Cassell's description in 1982 of the nature of suffering and the
      goals of medicine. Nurses play a fundamental role in caring for those who suffer.
      Suffering is associated with loss, intense emotions, spiritual distress, and
      inability to express those experiences. CONCLUSIONS: The 10 basic tenets of
      suffering describe its nature and the goals of nursing; they include listening,
      intimate care of the body, and presence. IMPLICATIONS FOR NURSING: Oncology
      nurses witness suffering in their daily work. This article is intended to
      acknowledge suffering experienced in oncology nursing and to stimulate future
      research.

PMID- 18321837
TI  - Trends in clinical practice and nurses' attitudes about fertility preservation
      for pediatric patients with cancer.
AB  - PURPOSE/OBJECTIVES: To examine trends in fertility preservation attitudes and
      behaviors of pediatric oncology nurses and evaluate their awareness of fertility
      preservation guidelines published in June 2006 by the American Society of
      Clinical Oncology (ASCO). DESIGN: Cross-sectional surveys conducted in 2005 and
      2006. SETTING: Annual meetings of the Florida Association of Pediatric Tumor
      Programs. SAMPLE: 115 pediatric oncology nurses in 2005 and 95 nurses in 2006.
      METHODS: A 45-item survey was distributed to conference attendees. MAIN RESEARCH
      VARIABLES: Knowledge, current fertility preservation practices, and awareness of
      fertility preservation guidelines. FINDINGS: Nurses' attitudes about fertility
      preservation discussions with patients did not change during the survey period;
      however, the number of nurses believing that one of their duties was to discuss
      fertility preservation with patients decreased from 91% in 2005 to 81% in 2006.
      Nurses' likelihood to discuss fertility preservation with patients with specific
      characteristics significantly changed over time. Fertility preservation
      discussions were just as likely for single patients as they were for those
      married or recently engaged, although nurses were more likely to discuss
      fertility preservation with patients who had at least one child or who had a poor
      prognosis. Nurses' awareness of ASCO guidelines was less than 5%. CONCLUSIONS: A
      majority of nurses perceive that fertility preservation options should be offered
      to patients. However, practice and patient family barriers exist that may impede
      discussion. Attitudes and behaviors will be monitored with the 2006 ASCO
      guidelines. IMPLICATIONS FOR NURSING: Nurses play a key role in survivorship
      discussions for pediatric patients with cancer and their families. Increased
      knowledge of fertility preservation guidelines may help promote the fertility
      preservation concept and lead to improved dissemination and implementation of
      training programs that focus on current ASCO fertility preservation guidelines
      and address the psychosocial needs of children aged 12-16 years.

PMID- 18321838
TI  - Storytelling intervention for patients with cancer: part 1--development and
      implementation.
AB  - PURPOSE/OBJECTIVES: To develop a nurse-led storytelling intervention for patients
      with cancer and implement the intervention using trained oncology nurses. DESIGN:
      Descriptive pilot project using qualitative methods to assess implementation of
      an intervention tool kit, with investigators blinded to control and intervention
      group membership. SETTING: Local regional medical center in the Pacific Northwest
      region of the United States. SAMPLE: A convenience sample of 11 patients with
      various cancer diagnoses was used for tool kit generation. Intervention and
      control groups were then formed and used to study tool kit implementation.
      METHODS: Participant exit interviews and facilitator debriefing questionnaires
      assessed the ability of a nurse facilitator to use a group storytelling
      intervention tool kit. Data from control and intervention groups were analyzed
      and compared with qualitative procedures. MAIN RESEARCH VARIABLES: A nurse-led
      storytelling intervention. FINDINGS: Analysis of interviews and questionnaires
      revealed implementation of storytelling tool kit principles and differences
      between storytelling and control groups in three patterns: finding a soft place
      to fall, understanding the cancer experience, and figuring out how (if) to get
      through it. CONCLUSIONS: Techniques contained in the tool kit were implemented
      and deemed clinically useful by oncology nurses. IMPLICATIONS FOR NURSING: Given
      the small testing groups, pilot project results must be interpreted with caution,
      but with additional research and instructional development, the tool kit could be
      useful to nurses in a variety of settings and locales.

PMID- 18321839
TI  - Storytelling intervention for patients with cancer: part 2--pilot testing.
AB  - PURPOSE/OBJECTIVES: To evaluate symptom reports and the impact of a nurse-led
      storytelling intervention in a supportive group setting on mood, stress level,
      coping with stress, pain, self-efficacy, and satisfaction with life in patients
      with cancer. DESIGN: Descriptive pilot project using a pretest/post-test control
      group. SETTING: Local regional medical center in the Pacific Northwest region of
      the United States. SAMPLE: Convenience sample of 10 patients with various cancer
      diagnoses; 7 completed the intervention. METHODS: Participants were randomly
      assigned to a storytelling or control group. Using a tool kit generated for this
      project, a nurse facilitator guided storytelling group participants in 12 1.5
      hour sessions. Six instruments, symptom assessments, and a retrospective
      physician chart review were completed for each group. Data were analyzed using
      repeated measures analysis of variance. MAIN RESEARCH VARIABLES: Mood, stress,
      coping, pain, self-efficacy, and satisfaction with life. FINDINGS: Comparison of
      changes in group mean scores revealed a significant decrease in anxiety in the
      storytelling group despite disease progression. Documentation of psychosocial
      symptomatology by physicians is limited; however, nursing assessments were useful
      in determining psychosocial status before and after the intervention.
      CONCLUSIONS: Results can be viewed only in context of a feasibility study and are
      not generalizable because of a limited sample size. A trained oncology nurse was
      able to use the storytelling intervention. Initial results are promising and
      warrant further study. IMPLICATIONS FOR NURSING: After additional testing, the
      intervention could be used to enhance storytelling groups for patients with
      cancer or for individuals who are uncomfortable in or do not have access to
      storytelling groups.

PMID- 18321840
TI  - Symptom clustering in older Taiwanese children with cancer.
AB  - PURPOSE/OBJECTIVES: To derive symptom clusters occurring in a large group of
      older pediatric patients with cancer in Taiwan and to examine whether each
      cluster differed based on gender, type of cancer and disease, pain, and
      functional status. DESIGN: Descriptive, correlational study. SETTING: Pediatric
      oncology inpatient unit and outpatient clinics in Taiwan. SAMPLE: 144 pediatric
      patients with cancer, aged 10-18 years. METHODS: Subjects completed the Memorial
      Symptom Assessment Scale 10-18, the Play Performance Scale for Children, and a
      demographic questionnaire. Medical records provided disease and treatment data.
      Cluster analysis techniques were used to identify the symptoms that clustered
      together by demographic characteristics, as well as disease, pain, and functional
      status. MAIN RESEARCH VARIABLES: Symptom cluster, pain status, and functional
      status. FINDINGS: Five clusters were identified from the statistical analysis.
      The symptoms that clustered together were somewhat surprising, and some can be
      explained by cultural differences. Patients with pain reported statistically
      significant higher distress in all five clusters. CONCLUSIONS: Five symptom
      clusters are identified in older Taiwanese children with cancer. The way and
      possible rationale of how these symptoms clustered together is discussed.
      IMPLICATIONS FOR NURSING: This is the first study that used a statistical
      procedure to derive symptom clusters experienced by pediatric oncology patients.
      Knowledge from this study can provide a starting point to investigate the
      stability of symptom clusters with different states of disease, different
      populations, and over various periods of time.

PMID- 18321843
TI  - Comment on: unexpected antimicrobial effect of statins.

PMID- 18321844
TI  - Imaging evaluation of foot and ankle pathology: self-assessment module.
AB  - The educational objectives of this self-assessment module are for the participant
      to exercise, self-assess, and improve his or her understanding of the imaging
      evaluation of foot and ankle pathology.

PMID- 18321845
TI  - Methodology and application of clinical trials in radiology: self-assessment
      module.
AB  - The educational objectives of this self-assessment module are for the participant
      to understand the differences between cohort and case-control studies in
      radiology, to understand the advantages of randomized controlled trials over
      observational studies, to understand the basic principles underlying the use of
      imaging examinations for screening asymptomatic populations for particular
      diseases, and to understand the biases associated with the use of survival
      statistics in the evaluation of screening.

PMID- 18321846
TI  - Methodology and application of prospective reader studies: self-assessment
      module.
AB  - The educational objectives of this self-assessment module are for the participant
      to read selected sources on prospective reader study methodologies and to self
      assess and improve his or her knowledge of this subject.

PMID- 18321847
TI  - Imaging of sarcoidosis: self-assessment module.
AB  - The educational objectives for this self-assessment module are for the
      participant to exercise, self-assess, and improve his or her understanding of the
      imaging features of sarcoidosis and the role of imaging in the clinical
      management of patients with sarcoidosis.

PMID- 18321848
TI  - Restoration of electrical diastole with bi-ventricular pacing.

PMID- 18321849
TI  - Protein kinase Czeta-dependent LKB1 serine 428 phosphorylation increases LKB1
      nucleus export and apoptosis in endothelial cells.
AB  - LKB1 is a serine-threonine protein kinase that, when inhibited, may result in
      unregulated cell growth and tumor formation. However, how LKB1 is regulated
      remains poorly understood. The aim of the present study was to define the
      upstream signaling events responsible for peroxynitrite (ONOO(-))-induced LKB1
      activation. Exposure of cultured human umbilical vein endothelial cells to a low
      concentration of ONOO(-) (5 microM) significantly increased the phosphorylation
      of LKB1 at Ser(428) and protein kinase Czeta (PKCzeta) at Thr(410). These effects
      were accompanied by increased activity of the lipid phosphatase PTEN, decreased
      activity and phosphorylation (Ser(473)) of Akt, and induction of apoptosis. ONOO(
      ) enhanced Akt-Ser(473) phosphorylation in LKB1-deficient HeLa S3 cells or in
      HeLa S3 cells transfected with kinase-dead LKB1. Conversely, ONOO(-) inhibited
      Akt Ser(473) phosphorylation when wild type LKB1 were reintroduced in HeLa S3
      cells. Further analysis revealed that PKCzeta directly phosphorylated LKB1 at
      Ser(428) in vitro and in intact cells, resulting in increased PTEN
      phosphorylation at Ser(380)/Thr(382/383). Finally, ONOO(-) enhanced PKCzeta
      nuclear import and LKB1 nuclear export. We conclude that PKCzeta mediates LKB1
      dependent Akt inhibition in response to ONOO(-), resulting in endothelial
      apoptosis.

PMID- 18321850
TI  - Linoleic acid induces calcium signaling, Src kinase phosphorylation, and
      neurotransmitter release in mouse CD36-positive gustatory cells.
AB  - We have recently demonstrated that the cells expressing CD36, localized apically
      on the taste buds of mouse lingual circumvallate papillae, act as gustatory
      cells. In the present study we isolated these CD36-positive cells from mouse
      circumvallate papillae and investigated intracellular signaling events, triggered
      by a long-chain polyunsaturated fatty acid, i.e. linoleic acid (LA). LA induced
      increases in free intracellular calcium concentrations, [Ca(2+)](i), by
      recruiting calcium from endoplasmic reticulum pool via inositol 1,4,5
      triphosphate production followed by calcium influx via opening of store-operated
      calcium (SOC) channels. LA also induced phosphorylation of Src-protein-tyrosine
      kinases (Src-PTKs), particularly of Fyn(59) and Yes(62). LA-evoked
      phosphorylation of Fyn(59) and Yes(62) was implicated in the activation of SOC
      channels. Reverse transcription-quantitative PCR revealed that the CD36-positive
      gustatory cells possessed mRNA of enzymes like tryptophan hydroxylase-1, l
      aromatic amino acid decarboxylase, tyrosine hydroxylase, and dopamine beta
      hydroxylase, involved in the synthesis of monoamine neurotransmitters.
      Interestingly, the addition of LA to these cells induced the release of 5
      hydroxytryptamine and noradrenalin to the extracellular environment. The LA
      induced release of these neurotransmitters was curtailed by SOC channel blockers
      and Src-PTK inhibitors. These results altogether demonstrate that LA binds to
      mouse CD36-positive gustatory cells, induces Src-PTKs phosphorylation, triggers
      calcium signaling, and evokes the release of 5-hydroxytryptamine and
      noradrenalin, which in turn may be implicated in the downstream signaling to the
      afferent nerve fibers, thus transmitting the output signal from taste buds to the
      central nervous system.

PMID- 18321851
TI  - Cue1p is an activator of Ubc7p E2 activity in vitro and in vivo.
AB  - Ubc7p is a ubiquitin-conjugating enzyme (E2) that functions with endoplasmic
      reticulum (ER)-resident ubiquitin ligases (E3s) to promote endoplasmic reticulum
      associated degradation (ERAD). Ubc7p only functions in ERAD if bound to the ER
      surface by Cue1p, a membrane-anchored ER protein. The role of Cue1p was thought
      to involve passive concentration of Ubc7p at the surface of the ER. However, our
      biochemical studies of Ubc7p suggested that Cue1p may, in addition, stimulate
      Ubc7p E2 activity. We have tested this idea and found it to be true both in vitro
      and in vivo. Ubc7p bound to the soluble domain of Cue1p showed strongly enhanced
      in vitro ubiquitination activity, both in the presence and absence of E3. Cue1p
      also enhanced Ubc7p function in vivo, and this activation was separable from the
      established ER-anchoring role of Cue1p. Finally, we tested in vivo activation of
      Ubc7p by Cue1p in an assay independent of the ER membrane and ERAD. A chimeric E2
      linking Ubc7p to the Cdc34p/Ubc3p localization domain complemented the cdc34-2 TS
      phenotype, and co-expression of the soluble Cue1p domain enhanced complementation
      by this chimeric Ubc7p E2. These studies reveal a previously unobserved
      stimulation of Ubc7p E2 activity by Cue1p that is critical for full ERAD and that
      functions independently of the well known Cue1p anchoring function. Moreover, it
      suggests a previously unappreciated mode for regulation of E2s by Cue1p-like
      interacting partners.

PMID- 18321852
TI  - Clusterin activates survival through the phosphatidylinositol 3-kinase/Akt
      pathway.
AB  - Clusterin is, in its major form, a secreted heterodimeric disulfide-linked
      glycoprotein (75-80 kDa). It was first linked to cell death in the rat ventral
      prostate after androgen deprivation. Recent studies have demonstrated that
      overexpression of clusterin in prostatic cells protects them against tumor
      necrosis factor-alpha (TNFalpha)-induced apoptosis. However the details of this
      survival mechanism remain undefined. Here, we investigate how clusterin prevents
      cells from undergoing TNFalpha-induced apoptosis. We established a double-stable
      prostatic cell line for inducible clusterin by using the Tet-On gene expression
      system. We demonstrated that 50% of the cells overexpressing clusterin escaped
      from TNFalpha- and actinomycin D-induced cell death. Moreover we demonstrated
      that the incubation of MLL cells with conditioned medium containing the secreted
      clusterin or the supplementation of purified clusterin in the extracellular
      medium decreased the TNFalpha-induced apoptosis significantly. This extracellular
      action implicates megalin, the putative membrane receptor for clusterin to
      mediate survival. Indeed clusterin overexpression up-regulated the expression of
      megalin and induced its phosphorylation in a dose-dependent manner. We
      interestingly showed that clusterin overexpression is associated with the up
      regulation of the phosphorylation of Akt. Activated Akt induced the
      phosphorylation of Bad and caused a decrease of cytochrome c release. These
      results enable us to pinpoint one mechanism by which secreted clusterin favors
      survival in androgen-independent prostate cancer cells, implicating its receptor
      megalin and Akt survival pathway.

PMID- 18321853
TI  - Calcineurin B homologous protein 3 promotes the biosynthetic maturation, cell
      surface stability, and optimal transport of the Na+/H+ exchanger NHE1 isoform.
AB  - Calcineurin B homologous protein (CHP) 1 and 2 are Ca(2+)-binding proteins that
      modulate several cellular processes, including cytoplasmic pH by positively
      regulating plasma membrane-type Na(+)/H(+) exchangers (NHEs). Recently another
      CHP-related protein, termed tescalcin or CHP3, was also shown to interact with
      the ubiquitous NHE1 isoform, but seemingly suppressed its activity. However, the
      precise physical and functional nature of this association was not examined in
      detail. In this study, biochemical and cellular studies were undertaken to
      further delineate this relationship. Glutathione S-transferase-NHE1 fusion
      protein pulldown assays revealed that full-length CHP3 binds directly to the
      proximal juxtamembrane C-terminal region (amino acids 505-571) of rat NHE1 in the
      same region that binds CHP1 and CHP2. The interaction was further validated by
      coimmunoprecipitation and coimmunolocalization experiments using full-length CHP3
      and wild-type NHE1 in transfected Chinese hamster ovary AP-1 cells. Simultaneous
      mutation of four hydrophobic residues within this region ((530)FLDHLL(535)) to
      either Ala, Gln, or Arg (FL-A, FL-Q, or FL-R) abrogated this interaction both in
      vitro and in intact cells. The NHE1 mutants were sorted properly to the cell
      surface but showed markedly reduced (FL-A) or minimal (FL-R and FL-Q) activity.
      Interestingly, and contrary to an earlier finding, ectopic coexpression of CHP3
      up-regulated the cell surface activity of wild-type NHE1. This stimulation was
      not observed with the CHP3 binding-defective mutants. Mechanistically,
      overexpression of CHP3 did not alter the H(+) sensitivity of wild-type NHE1 but
      rather promoted its biosynthetic maturation and half-life at the cell surface,
      thereby increasing the steady-state abundance of functional NHE1 protein.

PMID- 18321854
TI  - Signaling of a varicelloviral factor across the endoplasmic reticulum membrane
      induces destruction of the peptide-loading complex and immune evasion.
AB  - Cytotoxic T lymphocytes eliminate infected cells upon surface display of
      antigenic peptides on major histocompatibility complex I molecules. To promote
      immune evasion, UL49.5 of several varicelloviruses interferes with the pathway of
      major histocompatibility complex I antigen processing. However, the inhibition
      mechanism has not been elucidated yet. Within the macromolecular peptide-loading
      complex we identified the transporter associated with antigen processing (TAP1
      and TAP2) as the prime target of UL49.5. Moreover, we determined the active
      oligomeric state and crucial elements of the viral factor. Remarkably, the last
      two residues of the cytosolic tail of UL49.5 are essential for endoplasmic
      reticulum (ER)-associated proteasomal degradation of TAP. However, this process
      strictly requires additional signaling of an upstream regulatory element in the
      ER lumenal domain of UL49.5. Within this new immune evasion mechanism, we show
      for the first time that additive elements of a small viral factor and their
      signaling across the ER membrane are essential for targeted degradation of a
      multi-subunit membrane complex.

PMID- 18321855
TI  - Polycystin-1 regulates skeletogenesis through stimulation of the osteoblast
      specific transcription factor RUNX2-II.
AB  - Polycystin-1 (PC1) may play an important role in skeletogenesis through
      regulation of the bone-specific transcription factor Runx2-II. In the current
      study we found that PC1 co-localizes with the calcium channel polycystin-2 (PC2)
      in primary cilia of MC3T3-E1 osteoblasts. To establish the role of Runx2-II in
      mediating PC1 effects on bone, we crossed heterozygous Pkd1(m1Bei) and Runx2-II
      mice to create double heterozygous mice (Pkd1(+/m1Bei)/Runx2-II(+/-)) deficient
      in both PC1 and Runx2-II. Pkd1(+/m1Bei)/Runx2-II(+/-) mice exhibited additive
      reductions in Runx2-II expression that was associated with impaired endochondral
      bone development, defective osteoblast-mediated bone formation, and osteopenia.
      In addition, we found that basal intracellular calcium levels were reduced in
      homozygous Pkd1(m1Bei) osteoblasts. In contrast, overexpression of a PC1 C-tail
      construct increased intracellular calcium and selectively stimulated Runx2-II P1
      promoter activity in osteoblasts through a calcium-dependent mechanism. Site
      directed mutagenesis of critical amino acids in the coiled-coil domain of PC1
      required for coupling to PC2 abolished PC1-mediated Runx2-II P1 promoter
      activity. Additional promoter analysis mapped the PC1-responsive region to the
      "osteoblast-specific" enhancer element between -420 and -350 bp that contains NFI
      and AP-1 binding sites. Chromatin immunoprecipitation assays confirmed the
      calcium-dependent binding of NFI to this region. These findings indicate that PC1
      regulates osteoblast function through intracellular calcium-dependent control of
      Runx2-II expression. The overall function of the primary cilium-polycystin
      complex may be to sense and transduce environmental clues into signals regulating
      osteoblast differentiation and bone development.

PMID- 18321856
TI  - Identification of a glycine motif required for packing in EmrE, a multidrug
      transporter from Escherichia coli.
AB  - Glycine residues may play functional and structural roles in membrane proteins.
      In this work we studied the role of glycine residues in EmrE, a small multidrug
      transporter from Escherichia coli. EmrE extrudes various drugs across the plasma
      membrane in exchange with protons and, as a result, confers resistance against
      their toxic effects. Each of 12 glycine residues was replaced by site-directed
      mutagenesis. Four of the 12 glycine residues in EmrE are evolutionary conserved
      within the small multidrug resistance family of multidrug transporters. Our
      analysis reveals that only two (Gly-67 and Gly-97) of these four highly conserved
      residues are essential for transporter activity. Moreover, two glycine positions
      that are less conserved, Gly-17 and Gly-90, demonstrate also a nil phenotype when
      substituted. Our present results identifying Gly-17 and Gly-67 as irreplaceable
      reinforce the importance of previously defined functional clusters. Two essential
      glycine residues, Gly-90 and Gly-97, form a protein motif in which glycine
      residues are separated by six other residues (GG7). Upon substitution of glycine
      in these positions, the protein ability to form dimers is impaired as evaluated
      by cross-linking and pull-down experiments.

PMID- 18321857
TI  - Nonpolyadenylated RNA polymerase II termination is induced by transcript
      cleavage.
AB  - Although the termination of transcription and 3' RNA processing of the eukaryotic
      mRNA has been linked to a polyadenylation signal and a transcript cleavage
      process, much less is known about the termination or processing of
      nonpolyadenylated RNA polymerase II transcripts. An efficiently expressed plasmid
      based expression system was used to study the termination and processing of
      Schizosaccharomyces pombe U3 small nucleolar RNA (snoRNA) transcripts in vivo.
      The termination assay was linked to cell transformation, and restriction fragment
      length polymorphism was used to determine levels of plasmid-derived U3 snoRNA.
      Mutation analyses in vivo indicate that the maturation of the 3' end is not
      directly dependent on an external cis-acting sequence or structure; rather, it is
      dependent on a transcript cleavage that can occur hundreds or even thousands of
      nucleotides downstream of the mature U3 snoRNA sequence. Similarly, termination
      is dependent on the same transcript cleavage that is localized in a hairpin
      structure that normally follows the 3' end of the U3 snoRNA but that also can be
      moved hundreds or thousands of nucleotides downstream. Both processes, however,
      can be induced simultaneously and equally efficiently with a single unrelated
      Pac1 endonuclease-labile structure. The results support a "reversed torpedoes"
      model in which a single cleavage allows exonucleases and/or other protein factors
      access to the transcript leading to transcription termination in one direction
      and RNA maturation in the other direction.

PMID- 18321858
TI  - Small molecule antagonizes autoinhibition and activates AMP-activated protein
      kinase in cells.
AB  - AMP-activated protein kinase (AMPK) serves as an energy sensor and is considered
      a promising drug target for treatment of type II diabetes and obesity. A previous
      report has shown that mammalian AMPK alpha1 catalytic subunit including
      autoinhibitory domain was inactive. To test the hypothesis that small molecules
      can activate AMPK through antagonizing the autoinhibition in alpha subunits, we
      screened a chemical library with inactive human alpha1(394) (alpha1, residues 1
      394) and found a novel small-molecule activator, PT1, which dose-dependently
      activated AMPK alpha1(394), alpha1(335), alpha2(398), and even heterotrimer
      alpha1beta1gamma1. Based on PT1-docked AMPK alpha1 subunit structure model and
      different mutations, we found PT1 might interact with Glu-96 and Lys-156 residues
      near the autoinhibitory domain and directly relieve autoinhibition. Further
      studies using L6 myotubes showed that the phosphorylation of AMPK and its
      downstream substrate, acetyl-CoA carboxylase, were dose-dependently and time
      dependently increased by PT1 with-out an increase in cellular AMP:ATP ratio.
      Moreover, in HeLa cells deficient in LKB1, PT1 enhanced AMPK phosphorylation,
      which can be inhibited by the calcium/calmodulin-dependent protein kinase kinases
      inhibitor STO-609 and AMPK inhibitor compound C. PT1 also lowered hepatic lipid
      content in a dose-dependent manner through AMPK activation in HepG2 cells, and
      this effect was diminished by compound C. Taken together, these data indicate
      that this small-molecule activator may directly activate AMPK via antagonizing
      the autoinhibition in vitro and in cells. This compound highlights the effort to
      discover novel AMPK activators and can be a useful tool for elucidating the
      mechanism responsible for conformational change and autoinhibitory regulation of
      AMPK.

PMID- 18321859
TI  - Identification of human T cell receptor gammadelta-recognized epitopes/proteins
      via CDR3delta peptide-based immunobiochemical strategy.
AB  - Human T lymphocytes, bearing T cell receptor (TCR) gammadelta, play an important
      role in anti-tumor/microbe immune responses. However, few tumor antigens
      recognized by TCRgammadelta have been defined so far. To investigate antigenic
      epitopes/proteins recognized by gammadeltaT cells, we have established a new
      immunobiochemical strategy that uses complementarity-determining region 3 of TCR
      delta chain (CDR3delta) peptide-mediated epitope/protein-binding assays.
      CDR3delta peptides synthesized using the CDR3 region in TCR Vdelta2 chain were
      validated for their binding specificity to target cells or tissues. These
      CDR3delta peptides were then employed as probes to pan putative epitopes in a 12
      mer random peptide phage-displayed library and to identify putative protein
      ligands within tumor protein extracts by affinity chromatography and liquid
      chromatography/electrospray ionization-tandem mass spectrometry analysis. As a
      result, we have identified nine peptides and two proteins for TCRgammadelta,
      including human mutS homolog 2 (hMSH2) and heat shock protein (HSP) 60. All nine
      tested epitope peptides not only bind to gammadeltaT cells but also functionally
      activate gammadeltaT cells in vitro. Identification of HSP60 confirms the
      validity of this method as HSP60 is an identified ligand for TCRgammadelta. We
      show that hMSH2 is expressed on the surface of SKOV3 tumor cells, and
      cytotoxicity of Vdelta2 gammadeltaT cells to SKOV3 cells was blocked by anti
      hMSH2 antibody, suggesting that hMSH2 may be a new ligand for TCRgammadelta.
      Taken together, our findings provide a novel immunobiochemical strategy to
      identify epitopes/proteins recognized by gammadeltaT cells.

PMID- 18321860
TI  - The functional role of the second NPXY motif of the LRP1 beta-chain in tissue
      type plasminogen activator-mediated activation of N-methyl-D-aspartate receptors.
AB  - The low density lipoprotein receptor-related protein 1 (LRP1) emerges to play
      fundamental roles in cellular signaling pathways in the brain. One of its
      prominent ligands is the serine proteinase tissue-type plasminogen activator
      (tPA), which has been shown to act as a key activator of neuronal mitogen
      activated protein kinase pathways via the N-methyl-D-aspartate (NMDA) receptor.
      However, here we set out to examine whether LRP1 and the NMDA receptor might
      eventually act in a combined fashion to mediate tPA downstream signaling. By
      blocking tPA from binding to LRP1 using the receptor-associated protein, we were
      able to completely inhibit NMDA receptor activation. Additionally, inhibition of
      NMDA receptor calcium influx with MK-801 resulted in dramatic reduction of tPA
      mediated downstream signaling. This indicates a functional interaction between
      the two receptors, since both experimental approaches resulted in strongly
      reduced calcium influx and Erk1/2 phosphorylation. Additionally, we were able to
      inhibit Erk1/2 activation by competing for the LRP1 C-terminal binding motif with
      a truncated PSD95 construct resembling its PDZ III domain. Furthermore, we
      identified the distal NPXY amino acid motif in the C terminus of LRP1 as the
      crucial element for LRP1-NMDA receptor interaction via the adaptor protein PSD95.
      These results provide new insights into the mechanism of a tPA-induced, LRP1
      mediated gating mechanism for NMDA receptors.

PMID- 18321861
TI  - Inhibition of the human thioredoxin system. A molecular mechanism of mercury
      toxicity.
AB  - Mercury toxicity mediated by different forms of mercury is a major health
      problem; however, the molecular mechanisms underlying toxicity remain elusive. We
      analyzed the effects of mercuric chloride (HgCl(2)) and monomethylmercury (MeHg)
      on the proteins of the mammalian thioredoxin system, thioredoxin reductase (TrxR)
      and thioredoxin (Trx), and of the glutaredoxin system, glutathione reductase (GR)
      and glutaredoxin (Grx). HgCl(2) and MeHg inhibited recombinant rat TrxR with
      IC(50) values of 7.2 and 19.7 nm, respectively. Fully reduced human Trx1 bound
      mercury and lost all five free thiols and activity after incubation with HgCl(2)
      or MeHg, but only HgCl(2) generated dimers. Mass spectra analysis demonstrated
      binding of 2.5 mol of Hg(2+) and 5 mol of MeHg(+)/mol of Trx1 with the very
      strong Hg(2+) complexes involving active site and structural disulfides.
      Inhibition of both TrxR and Trx activity was observed in HeLa and HEK 293 cells
      treated with HgCl(2) or MeHg. GR was inhibited by HgCl(2) and MeHg in vitro, but
      no decrease in GR activity was detected in cell extracts treated with mercurials.
      Human Grx1 showed similar reactivity as Trx1 with both mercurial compounds, with
      the loss of all free thiols and Grx dimerization in the presence of HgCl(2), but
      no inhibition of Grx activity was observed in lysates of HeLa cells exposed to
      mercury. Overall, mercury inhibition was selective toward the thioredoxin system.
      In particular, the remarkable potency of the mercury compounds to bind to the
      selenol-thiol in the active site of TrxR should be a major molecular mechanism of
      mercury toxicity.

PMID- 18321862
TI  - Structural basis for Ufm1 processing by UfSP1.
AB  - Ubiquitin-fold modifier 1 (Ufm1) is a newly identified ubiquitin-like protein.
      Like ubiquitin and other ubiquitin-like proteins, Ufm1 is synthesized as a
      precursor that needs to be processed to expose the conserved C-terminal glycine
      prior to its conjugation to target proteins. Two novel proteases, named UfSP1 and
      UfSP2, have been shown to be responsible for the release of Ufm1 from Ufm1
      conjugated cellular proteins as well as for the processing of its precursor. They
      show no sequence homology with known proteases. Here, we describe the 1.7A
      resolution crystal structure of mouse UfSP1, consisting of 217 amino acids. The
      structure reveals that it is a novel cysteine protease having a papain-like fold,
      with Cys(53), Asp(175), and His(177) that form a catalytic triad, and Tyr(41)
      that participates in the formation of the oxyanion hole. This differs from the
      canonical catalytic triad of papain-like proteases in that the aspartate and the
      histidine residues are from the "Asp-Pro-His" box. The Asp-Pro-His configuration
      seen in UfSP1, together with Atg4B and M48(USP), seem to form a new subfamily of
      the cysteine protease superfamily. The mutagenesis study of the active site
      residues confirms structural basis for catalysis. The interaction between UfSP1
      and Ufm1 appears quite substantial, since the K(D) value was estimated to be 1.6
      mum by the isothermal titration calorimetry analysis. Furthermore, the NMR data
      shows that the loop between beta3 and alpha2 in addition to the C-terminal region
      of Ufm1 plays a role in binding to UfSP1.

PMID- 18321863
TI  - Stabilization of RelB requires multidomain interactions with p100/p52.
AB  - The NF-kappaB family member RelB has many properties not shared by other family
      members such as restricted subunit association and lack of regulation by the
      classical IkappaB proteins. We show that the protein level of RelB is
      significantly reduced in the absence of p100 and reduced even more when both p100
      and p105 are absent. RelB stabilizes itself by directly interacting with p100,
      p105, and their processed products. However, RelB forms complexes with its
      partners using different interaction modes. Although the C-terminal ankyrin
      repeat domain of p105 is not involved in the RelB-p105 complex formation, all
      domains and flexible regions of each protein are engaged in the RelB-p100
      complex. In several respects the RelB-p52 and RelB-p100 complexes are unique in
      the NF-kappaB family. The N-terminal domain of p100/p52 interacts with RelB but
      not RelA. The transcriptional activation domain of RelB, but not RelA, directly
      interacts with the processing region of p100. These unique protein-protein
      contacts explain why RelB prefers p52 as its dimeric partner for transcriptional
      activity and is retained in the cytoplasm as an inhibited complex by p100. This
      association-mediated stabilization of RelB implies a possible role for RelB in
      the processing of p100 into p52.

PMID- 18321864
TI  - A partial loss of function allele of methyl-CpG-binding protein 2 predicts a
      human neurodevelopmental syndrome.
AB  - Rett Syndrome, an X-linked dominant neurodevelopmental disorder characterized by
      regression of language and hand use, is primarily caused by mutations in methyl
      CpG-binding protein 2 (MECP2). Loss of function mutations in MECP2 are also found
      in other neurodevelopmental disorders such as autism, Angelman-like syndrome and
      non-specific mental retardation. Furthermore, duplication of the MECP2 genomic
      region results in mental retardation with speech and social problems. The common
      features of human neurodevelopmental disorders caused by the loss or increase of
      MeCP2 function suggest that even modest alterations of MeCP2 protein levels
      result in neurodevelopmental problems. To determine whether a small reduction in
      MeCP2 level has phenotypic consequences, we characterized a conditional mouse
      allele of Mecp2 that expresses 50% of the wild-type level of MeCP2. Upon careful
      behavioral analysis, mice that harbor this allele display a spectrum of
      abnormalities such as learning and motor deficits, decreased anxiety, altered
      social behavior and nest building, decreased pain recognition and disrupted
      breathing patterns. These results indicate that precise control of MeCP2 is
      critical for normal behavior and predict that human neurodevelopmental disorders
      will result from a subtle reduction in MeCP2 expression.

PMID- 18321865
TI  - Defective body-weight regulation, motor control and abnormal social interactions
      in Mecp2 hypomorphic mice.
AB  - MeCP2 is an abundant protein that binds to methylated cytosine residues in DNA
      and regulates transcription. Mutations in MECP2 cause Rett syndrome, a severe
      neurological disorder that affects approximately 1:10 000 females. Mice lacking
      MeCP2 have been generated and constitute important models of Rett syndrome.
      However, it is yet unclear whether certain physiological events are sensitive to
      a decrease, rather than a complete lack of MeCP2. Here we report that a Mecp2
      floxed allele (Mecp2(lox)) that was generated to allow conditional mutagenesis
      behaves as a hypomorph and the corresponding mutant mice exhibit phenotypical
      alterations including body weight gain, motor abnormalities and altered social
      behavior. Our data reinforce the view that the central nervous system is
      extremely sensitive to MeCP2 expression levels and suggest that the 3'-UTR of
      Mecp2 might contain important elements that contribute to the regulation of its
      stability or processing.

PMID- 18321866
TI  - Stoichiometric imbalance in the receptor complex contributes to dysfunctional
      BMPR-II mediated signalling in pulmonary arterial hypertension.
AB  - Heterozygous germline defects in a gene encoding a type II receptor for bone
      morphogenetic proteins (BMPR-II) underlie the majority of inherited cases of the
      vascular disorder known as pulmonary arterial hypertension (PAH). However, the
      precise molecular consequences of PAH causing mutations on the function of the
      receptor complex remain unclear. We employed novel enzymatic and fluorescence
      activity based techniques to assess the impact of PAH mutations on pre-mRNA
      splicing, nonsense-mediated decay (NMD) and receptor complex interactions. We
      demonstrate that nonsense and frameshift mutations trigger NMD, providing further
      evidence that haplo-insufficiency is a major molecular consequence of disease
      related BMPR2 mutations. We identified heterogeneous functional defects in BMPR
      II activity, including impaired type I receptor phosphorylation, receptor
      interactions and altered receptor complex stoichiometry leading to perturbation
      of downstream signalling pathways. Importantly, these studies demonstrate that
      the intracellular domain of BMPR-II is both necessary and sufficient for receptor
      complex interaction. Finally and to address the potential for resolution of
      stoichiometric balance, we investigated an agent that promotes translational
      readthrough of a BMPR2 nonsense reporter construct without interfering with the
      NMD pathway. We propose that stoichiometric imbalance, due to either haplo
      insufficiency or loss of optimal receptor-receptor interactions impairs BMPR-II
      mediated signalling in PAH. Taken together, these studies have identified an
      important target for early therapeutic intervention in familial PAH.

PMID- 18321867
TI  - Smoking and lymphoma risk in the European prospective investigation into cancer
      and nutrition.
AB  - Lymphomas are one of the few cancers that have been increasing in incidence over
      the past decades. So far, only a few established risk factors have been
      identified, including immunosuppression and viral infections. Recent evidence
      suggests etiologic heterogeneity of different lymphoma subtypes. Smoking may
      affect risk differently, depending on the lymphoma entity. The European
      Prospective Investigation into Cancer and Nutrition was used to study the role of
      smoking in the etiology of lymphomas and individual subtypes within a prospective
      study. Information on baseline and lifetime tobacco smoking by 478,590
      participants was collected between 1992 and 2000. Cox proportional hazards
      regression was used to calculate multivariate-adjusted hazard ratios and 95%
      confidence intervals. During 3,567,410 person-years of follow-up, 1,371 lymphoma
      cases (1,304 non-Hodgkin's lymphomas and 67 Hodgkin's lymphomas) were identified.
      Relative risk for smokers at recruitment was more than twofold higher for
      Hodgkin's lymphoma (hazard ratio = 2.14, 95% confidence interval: 1.18, 3.87) but
      was not elevated for non-Hodgkin's lymphoma (hazard ratio = 1.06, 95% confidence
      interval: 0.94, 1.19) and individual B-cell non-Hodgkin's lymphoma subtypes. In
      this prospective study, smoking appeared to increase Hodgkin's lymphoma risk
      consistently in both genders, whereas B-cell non-Hodgkin's lymphoma risk was not
      associated. Future analysis should involve viral biomarkers and genetic
      susceptibility markers to elucidate potential mechanisms of smoking-induced
      carcinogenesis, particularly for Hodgkin's lymphoma.

PMID- 18321868
TI  - Dietary curcumin modulates transcriptional regulators of phase I and phase II
      enzymes in benzo[a]pyrene-treated mice: mechanism of its anti-initiating action.
AB  - Curcumin has been shown to possess anti-initiating and anti-promoting activity in
      experimental systems. However, the mechanisms of its actions are not fully
      elucidated in vivo. In the present study, mechanisms of curcumin-mediated anti
      initiation were investigated in mice employing benzo[a]pyrene (B[a]P) as a model
      carcinogen. Dietary pretreatment of mice with chemopreventive doses of curcumin
      showed significant inhibition of B[a]P-induced enzyme activity, protein and
      messenger RNA (mRNA) levels of cytochrome P450 1A1/1A2 in liver and lungs.
      Although curcumin alone did not alter the basal levels of aryl hydrocarbon
      receptor (AhR), it significantly decreased the B[a]P-induced AhR protein levels,
      its phosphorylation, nuclear translocation and subsequent binding to DNA, thereby
      decreasing the transactivation of CYP1A. Dietary curcumin led to increase in NF
      E2-related factor-2 (Nrf2) protein levels and enhanced its nuclear translocation
      in liver and lungs of mice as compared with controls. Additionally, increased
      binding of Nrf2 to antioxidant response element occurred in nuclear extracts from
      liver and lungs of mice pretreated with dietary curcumin. Induction of activity,
      protein and mRNA levels of glutathione S-transferase, its isoforms and
      NAD(P)H:quinone oxidoreductase-1 by dietary curcumin in mice paralleled the
      curcumin-mediated activation of Nrf2, leading to increased detoxification of
      B[a]P. In agreement with the observed curcumin-mediated decrease in B[a]P-induced
      phase I enzyme and concomitant induction of phase II enzymes, pretreatment with
      dietary curcumin resulted in significant reduction of B[a]P-induced DNA adduct,
      oxidative damage and inflammation. To conclude, curcumin exhibits anti-initiating
      effects via modulating the transcriptional regulators of phase I and phase II
      enzymes in mice.

PMID- 18321869
TI  - Arsenite alters global histone H3 methylation.
AB  - Arsenic (As) is a well-characterized human carcinogen but is generally not
      mutagenic. The evidence that As induces both loss of global DNA methylation and
      gene promoter DNA hypermethylation has suggested that epigenetic mechanisms may
      play an important role in As-induced carcinogenesis. In the present study, we
      examined the change in histone methylation by As exposure. In human lung
      carcinoma A549 cells, exposure to inorganic trivalent As (arsenite) increased
      H3K9 dimethylation (H3K9me2) and decreased H3K27 trimethylation (H3K27me3), both
      of which represent gene silencing marks, while increasing the global levels of
      the H3K4 trimethylation (H3K4me3), a gene-activating mark. The increase in
      H3K9me2 was mediated by an increase in the histone methyltransferase G9a protein
      and messenger RNA levels. We also observed strikingly significant altered histone
      modifications induced by very low-dose (0.1 microM) arsenite. Taken together,
      these results suggest a potential mechanism by which As induces carcinogenesis
      through the alteration of specific histone methylations that represent both gene
      silencing and activating marks. Furthermore, these marks are known to affect DNA
      methylation, and it is likely that arsenic's effect is not limited to histone
      modifications alone, but extends, perhaps by them, to DNA methylations as well.
      Future studies in our laboratory will address the genomic location of these
      silencing and activating marks using ChIP-on-chip technology.

PMID- 18321870
TI  - Deficit in a neural correlate of reality monitoring in schizophrenia patients.
AB  - Patients who suffer from the devastating psychiatric illness schizophrenia are
      plagued by hallucinations, bizarre behavior, and delusional ideas, such as
      believing that they are controlled by malevolent outside forces. A fundamental
      human cognitive operation that may contribute to these hallmark symptoms is the
      ability to maintain accurate and coherent self-referential processing over time,
      such as occurs during reality monitoring (distinguishing self-generated from
      externally perceived information). However, the neural bases for a disturbance in
      this operation in schizophrenia have not been fully explored. Using functional
      magnetic resonance imaging, we asked clinically stable schizophrenia patients to
      remember whether or not they had generated a target word during an earlier
      sentence completion task. We found that, during accurate performance of this self
      referential source memory task, the schizophrenia subjects manifest a deficit in
      rostral medial prefrontal cortex (mPFC) activity--a brain region critically
      implicated in both the instantiation and the retrieval of self-referential
      information in healthy subjects. Impairment in rostral mPFC function likely plays
      a key role in the profound subjective disturbances that characterize
      schizophrenia and that are the aspect of the disorder most troubling to patients
      and to society at large.

PMID- 18321871
TI  - A rational account of memory predicts left prefrontal activation during
      controlled retrieval.
AB  - What is the role of the left prefrontal cortex in the controlled retrieval of
      learned information? We present a theory of declarative retrieval that posits
      that the amount of control exerted by this region during retrieval is inversely
      proportional to 1) the frequency and recency of previous experiences with the
      retrieved memory and 2) the associative strength between the current context and
      the retrieved memory. This theory is rational in the sense that it claims that
      declarative retrieval is highly sensitive to the statistical regularities in the
      environment. We demonstrate how our theory produces precise predictions of
      response time and neural activity during recall and test these predictions in an
      experiment that manipulates the frequency of previous experiences and the
      associative strength to the retrieval cues. Our findings suggest that the control
      process performed by the left prefrontal cortex directly reflects the demands of
      the environment on memory.

PMID- 18321872
TI  - Dopaminergic modulation of auditory cortex-dependent memory consolidation through
      mTOR.
AB  - Previous studies in the auditory cortex of Mongolian gerbils on discrimination
      learning of the direction of frequency-modulated tones (FMs) revealed that long
      term memory formation involves activation of the dopaminergic system, activity of
      the protein kinase mammalian target of rapamycin (mTOR), and protein synthesis.
      This led to the hypothesis that the dopaminergic system might modulate memory
      formation via regulation of mTOR, which is implicated in translational control.
      Here, we report that the D1/D5 dopamine receptor agonist SKF-38393 substantially
      improved gerbils' FM discrimination learning when administered systemically or
      locally into the auditory cortex shortly before, shortly after, or 1 day before
      conditioning. Although acquisition performance during initial training was
      normal, the discrimination of FMs was enhanced during retraining performed hours
      or days after agonist injection compared with vehicle-injected controls. The
      D1/D5 receptor antagonist SCH-23390, the mTOR inhibitor rapamycin, and the
      protein synthesis blocker anisomycin suppressed this effect. By
      immunohistochemistry, D1 dopamine receptors were identified in the gerbil
      auditory cortex predominantly in the infragranular layers. Together, these
      findings suggest that in the gerbil auditory cortex dopaminergic inputs regulate
      mTOR-mediated, protein synthesis-dependent mechanisms, thus controlling for hours
      or days the consolidation of memory required for the discrimination of complex
      auditory stimuli.

PMID- 18321873
TI  - Organizational principles of human visual cortex revealed by receptor mapping.
AB  - This receptorarchitectonic study of the human visual cortex investigated
      interareal differences in mean receptor concentrations and laminar distribution
      patterns of 16 neurotransmitter receptors in the dorsal and ventral parts of
      areas V1, V2, V3 as well as in adjoining areas V4 (ventrally) and V3A (dorsally).
      Both the functional hierarchy of these areas and a distinction between dorsal and
      ventral visual cortices were reflected by significant receptorarchitectonic
      differences. The observation that dorso-ventral differences existed in all
      extrastriate areas (including V2) is particularly important for the discussion
      about the relationship between dorsal and ventral V3 as it indicates that a
      receptorarchitectonic distinction between the ventral and dorsal visual cortices
      is present in but not specific to V3. This molecular specificity is mirrored by
      previously reported differences in retinal microstructure and functional
      differences as revealed in behavioral experiments demonstrating differential
      advantages for stimulus processing in the upper and lower visual fields. We argue
      that these anatomical and functional differences may be regarded as the result of
      an evolutionary optimization adapting to the processing of the most relevant
      stimuli occurring in the upper and lower visual fields.

PMID- 18321874
TI  - Spatial attention modulates initial afferent activity in human primary visual
      cortex.
AB  - It is well established that spatially directed attention enhances visual
      perceptual processing. However, the earliest level at which processing can be
      affected remains unknown. To date, there has been no report of modulation of the
      earliest visual event-related potential component "C1" in humans, which indexes
      initial afference in primary visual cortex (V1). Thus it has been suggested that
      initial V1 activity is impenetrable, and that the earliest modulations occur in
      extrastriate cortex. However, the C1 is highly variable across individuals, to
      the extent that uniform measurement across a group may poorly reflect the
      dynamics of V1 activity. In the present study we employed an individualized
      mapping procedure to control for such variability. Parameters for optimal C1
      measurement were determined in an independent, preliminary "probe" session and
      later applied in a follow-up session involving a spatial cueing task. In the
      spatial task, subjects were cued on each trial to direct attention toward 1 of 2
      locations in anticipation of an imperative Gabor stimulus and were required to
      detect a region of lower luminance appearing within the Gabor pattern 30% of the
      time at the cued location only. Our data show robust spatial attentional
      enhancement of the C1, beginning as early as its point of onset (57 ms). Source
      analysis of the attentional modulations points to generation in striate cortex.
      This finding demonstrates that at the very moment that visual information first
      arrives in cortex, it is already being shaped by the brain's attentional biases.

PMID- 18321875
TI  - Learning-dependent, transient increase of activity in noradrenergic neurons of
      locus coeruleus during slow wave sleep in the rat: brain stem-cortex interplay
      for memory consolidation?
AB  - Memory consolidation during sleep is regaining attention due to a wave of recent
      reports of memory improvements after sleep or deficits after sleep disturbance.
      Neuromodulators have been proposed as possible players in this putative off-line
      memory processing, without much experimental evidence. We recorded neuronal
      activity in the rat noradrenergic nucleus locus coeruleus (LC) using chronically
      implanted movable microelectrodes while monitoring the behavioral state via
      electrocorticogram and online video recording. Extracellular recordings of
      physiologically identified noradrenergic neurons of LC were made in freely
      behaving rats for 3 h before and after olfactory discrimination learning. On
      subsequent days, if LC recording remained stable, additional learning sessions
      were made within the olfactory discrimination protocol, including extinction,
      reversals, learning new odors. Contrary to the long-standing dogma about the
      quiescence of noradrenergic neurons of LC, we found a transient increase in LC
      activity in trained rats during slow wave sleep (SWS) 2 h after learning. The
      discovery of learning-dependent engagement of LC neurons during SWS encourages
      exploration of brain stem-cortical interaction during this delayed phase of
      memory consolidation and should bring new insights into mechanisms underlying
      memory formation.

PMID- 18321876
TI  - Astrocytes discriminate and selectively respond to the activity of a
      subpopulation of neurons within the barrel cortex.
AB  - Sensory information from single whiskers in rodents projects to defined
      morphological units in the cortex, the barrels. We found that astrocytes
      selectively respond with an increase in the cytosolic Ca(2+) concentration to
      activation of layer 4 neurons, the input cells of the barrel columns. The
      neuronal Ca(2+) signal also spread across barrel column borders mainly in layer
      2/3, but the glutamate-mediated astrocyte response stayed restricted to the
      barrel column. In contrast, when interfering with inhibitory pathways by blocking
      either purinergic, adenosine or gamma-aminobutyric acid(A) receptors, the
      stimulation activated a Ca(2+) response in a much larger astrocyte population no
      longer restricted to the borders of the barrel column. We also observed
      spontaneous and evoked Ca(2+) activity in the synaptic target cells of layer 4
      neurons, the layer 2/3 pyramidal cells, but again, we never recorded Ca(2+)
      responses in astrocytes following activity in this neuronal population. Our data
      show that astrocytes can discriminate and selectively respond to the activity of
      a subpopulation of excitatory neurons within a given brain region. This
      selectivity in the astrocyte response describes a new level of complexity and
      integration in the reaction of astrocytes to neuronal activity.

PMID- 18321877
TI  - Radiation detector developments in medical applications: inorganic scintillators
      in positron emission tomography.
AB  - In recent years, a number of new gamma-ray scintillators are commercially
      available. These scintillators are either derived from known scintillators, e.g.
      Lu1-xYxAlO3: Ce (LuYAP) from LuAlO3:Ce and Lu(2(1-x))Y2xSiO5:Ce (LYSO) from
      Lu2SiO5:Ce or are the result of new discoveries, e.g. LaCl3:Ce and LaBr3:Ce. The
      first two materials are primarily of interest because of the relatively high
      detection efficiency and fast response; LYSO has found application in time-of
      flight (TOF) positron-emission tomography (TOF PET) and the LuYAP-LYSO
      combination is used in small-animal PET. The halide scintillators have an
      excellent energy resolution of approximately 3% at 662 keV and they have a
      relatively high light yield. LaBr3:Ce is being studied for application in TOF
      PET. At the same time, the search for and research on new scintillator materials
      are going on. For example, LuI3:Ce is a new material with a very high light yield
      (approximately 90,000 photons MeV(-1)). Other examples of new materials are
      (C6H13NH3)2PbI4 and (C3H7NH3)2PbBr4, organic-inorganic hybrid compounds, of which
      the former has a very fast sub-nanosecond response. The new scintillators show
      great promise for new developments in medical applications, in particular, for
      PET systems.

PMID- 18321878
TI  - Patient doses and image quality in digital chest radiology.
AB  - Chest X-ray examination is one of the most frequently required procedures used in
      clinical practice. For studying the image quality of different X-ray digital
      systems and for the control of patient doses during chest radiological
      examinations, the standard anthropomorphic lung/chest phantom RSD 330 has been
      used and exposed in different digital modalities available in Slovakia. To
      compare different techniques of chest examination, a special software has been
      developed that enables researchers to compare digital imaging and communications
      in medicine header images from different digital modalities, using a special
      viewer. In this paper, this special software has been used for an anonymous
      correspondent audit for testing image quality evaluation by comparing various
      parameters of chest imaging, evaluated by 84 Slovak radiologists. The results of
      the comparison have shown that the majority of the participating radiologists
      felt that the highest image quality is reached with a flat panel, assessed by the
      entrance surface dose value, which is approximately 75% lower than the diagnostic
      reference level of chest examination given in the Slovak legislation. Besides the
      results of the audit, the possibilities of using the software for optimisation,
      education and training of medical students, radiological assistants, physicists
      and radiologists in the field of digital radiology will be described.

PMID- 18321879
TI  - Improved performance of enzyme-linked immunosorbent assays and the effect of
      human immunodeficiency virus coinfection on the serologic detection of herpes
      simplex virus type 2 in Rakai, Uganda.
AB  - Ugandan subjects (820) were tested by Focus HerpeSelect enzyme-linked
      immunosorbent assay (ELISA), Kalon herpes simplex virus type 2 ELISA, and BioKit
      rapid test, and the results were compared to those of Western blotting. Higher
      than-standard-index cutoff values gave optimal sensitivity and specificity. Kalon
      ELISA was the optimal assay when an index value of 1.5 was used (sensitivity,
      91.7%; specificity, 92.4%).

PMID- 18321880
TI  - Measuring immunoglobulin g antibodies to tetanus toxin, diphtheria toxin, and
      pertussis toxin with single-antigen enzyme-linked immunosorbent assays and a bead
      based multiplex assay.
AB  - Bead-based assay systems offer the possibility of measuring several specific
      antibodies in one sample simultaneously. This study evaluated a vaccine panel of
      a multianalyte system that measures antibodies to tetanus toxin, diphtheria
      toxin, and pertussis toxin (PT) from Bordetella pertussis. The antibody
      concentrations of human immunoglobulin G (IgG) to PT, tetanus toxin, and
      diphtheria toxin were measured in 123 serum pairs (total of 246 sera) from a
      vaccine study. The multianalyte bead assay was compared to a standardized in
      house IgG- anti-PT enzyme-linked immunosorbent assay (ELISA) of the German
      reference laboratory for bordetellae, as well as to various commercially
      available ELISAs for anti-PT IgG, anti-tetanus IgG, and anti-diphtheria IgG. The
      results of the multiplex assay regarding the antibodies against diphtheria toxin
      compared favorably with a regression coefficient of 0.938 for values obtained
      with an ELISA from the same manufacturer used as a reference. Similarly,
      antibodies to tetanus toxin showed a correlation of 0.910 between the reference
      ELISA and the multianalyte assay. A correlation coefficient of 0.905 was found
      when an "in-house" IgG anti-PT and the multiplex assay were compared. Compared to
      single ELISA systems from two other manufacturers, the multiplex assay performed
      similarly well or better. The multianalyte assay system was a robust system with
      fast and accurate results, analyzing three parameters simultaneously in one
      sample. The system was well suited to quantitatively determine relevant vaccine
      induced antibodies compared to in-house and commercially available single-antigen
      ELISA systems.

PMID- 18321881
TI  - Prevalence of hepatitis E virus infection in children in the northeast of Spain.
AB  - The prevalence of immunoglobulin G (IgG) anti-hepatitis E virus (anti-HEV)
      antibodies was studied with a representative sample of 1,249 healthy children
      aged between 6 and 15 years. IgG anti-HEV antibodies were detected in 57 (4.6%)
      of the 1,249 samples analyzed, suggesting that some children are exposed to HEV
      in early childhood.

PMID- 18321882
TI  - Rapid point-of-care test to detect broad ranges of protective antigen-specific
      immunoglobulin G concentrations in recipients of the U.S.-licensed anthrax
      vaccine.
AB  - Currently, there is no routine monitoring of an immune response to the anthrax
      vaccine. Simple on-site tests are needed to evaluate the antibody response of
      anthrax-vaccinated individuals in the Armed Forces and others at high risk. Using
      a prototype lateral flow assay (LFA) (R. E. Biagini, D. L. Sammons, J. P. Smith,
      B. A. MacKenzie, C. A. F. Striley, J. E. Snawder, S. A. Robertson, and C. P.
      Quinn, Clin. Vaccine Immunol. 13:541-546, 2006), we investigated the agreement
      between a validated anthrax protective antigen (PA) immunoglobulin G (IgG) enzyme
      linked immunosorbent assay (ELISA) and the LFA for 335 unvaccinated and
      vaccinated subjects. We also investigated the performance of the LFA under the
      following conditions: thermal shock (i.e., thermal cycling between temperature
      extremes), high temperature/high relative humidity, high temperature/low relative
      humidity, and low temperature/low relative humidity. With the anti-PA ELISA used
      as a standard, the LFA was shown to be optimally diagnostic at 11 microg/ml anti
      PA-specific IgG. At this concentration, the LFA specificity and sensitivity were
      98% (95% confidence interval [CI], 97% to 100%) and 92% (CI, 88% to 97%),
      respectively. Receiver operating characteristic curve analysis yielded an area
      under the curve value of 0.988 (CI, 0.976 to 1.00), suggesting that the LFA is an
      extremely accurate diagnostic test. For < or = 4 or > or = 50 microg/ml PA
      specific IgG, the LFA results for each environmental condition were identical to
      those obtained in the laboratory. These data indicate that this rapid point-of
      care test would be a feasible tool in monitoring the serological antibody
      responses of individuals that have been vaccinated against anthrax.

PMID- 18321883
TI  - PedMine--a simulated annealing algorithm to identify maximally unrelated
      individuals in population isolates.
AB  - In family-based genetic studies, it is often useful to identify a subset of
      unrelated individuals. When such studies are conducted in population isolates,
      however, most if not all individuals are often detectably related to each other.
      To identify a set of maximally unrelated (or equivalently, minimally related)
      individuals, we have implemented simulated annealing, a general-purpose algorithm
      for solving difficult combinatorial optimization problems. We illustrate our
      method on data from a genetic study in the Old Order Amish of Lancaster County,
      Pennsylvania, a population isolate derived from a modest number of founders.
      Given one or more pedigrees, our program automatically and rapidly extracts a
      fixed number of maximally unrelated individuals. AVAILABILITY:
      http://www.hg.med.umich.edu/labs/douglaslab/software.html (version 1.0.0).

PMID- 18321884
TI  - e-LiSe--an online tool for finding needles in the '(Medline) haystack'.
AB  - Using literature databases one can find not only known and true relations between
      processes but also less studied, non-obvious associations. The main problem with
      discovering such type of relevant biological information is 'selection'. The
      ability to distinguish between a true correlation (e.g. between different types
      of biological processes) and random chance that this correlation is statistically
      significant is crucial for any bio-medical research, literature mining being no
      exception. This problem is especially visible when searching for information
      which has not been studied and described in many publications. Therefore, a novel
      bio-linguistic statistical method is required, capable of 'selecting' true
      correlations, even when they are low-frequency associations. In this article, we
      present such statistical approach based on Z-score and implemented in a web-based
      application 'e-LiSe'. AVAILABILITY: The software is available at
      http://miron.ibb.waw.pl/elise/

PMID- 18321885
TI  - BicOverlapper: a tool for bicluster visualization.
AB  - BicOverlapper is a tool to visualize biclusters from gene-expression matrices in
      a way that helps to compare biclustering methods, to unravel trends and to
      highlight relevant genes and conditions. A visual approach can complement
      biological and statistical analysis and reduce the time spent by specialists
      interpreting the results of biclustering algorithms. The technique is based on a
      force-directed graph where biclusters are represented as flexible overlapped
      groups of genes and conditions. AVAILABILITY: The BicOverlapper software and
      supplementary material are available at http://vis.usal.es/bicoverlapper

PMID- 18321886
TI  - Inference of biochemical network models in S-system using multiobjective
      optimization approach.
AB  - MOTIVATION: The inference of biochemical networks, such as gene regulatory
      networks, protein-protein interaction networks, and metabolic pathway networks,
      from time-course data is one of the main challenges in systems biology. The
      ultimate goal of inferred modeling is to obtain expressions that quantitatively
      understand every detail and principle of biological systems. To infer a
      realizable S-system structure, most articles have applied sums of magnitude of
      kinetic orders as a penalty term in the fitness evaluation. How to tune a penalty
      weight to yield a realizable model structure is the main issue for the inverse
      problem. No guideline has been published for tuning a suitable penalty weight to
      infer a suitable model structure of biochemical networks. RESULTS: We introduce
      an interactive inference algorithm to infer a realizable S-system structure for
      biochemical networks. The inference problem is formulated as a multiobjective
      optimization problem to minimize simultaneously the concentration error, slope
      error and interaction measure in order to find a suitable S-system model
      structure and its corresponding model parameters. The multiobjective optimization
      problem is solved by the epsilon-constraint method to minimize the interaction
      measure subject to the expectation constraints for the concentration and slope
      error criteria. The theorems serve to guarantee the minimum solution for the
      epsilon-constrained problem to achieve the minimum interaction network for the
      inference problem. The approach could avoid assigning a penalty weight for sums
      of magnitude of kinetic orders.

PMID- 18321887
TI  - Predicting proteolytic sites in extracellular proteins: only halfway there.
AB  - MOTIVATION: Many secretory proteins are synthesized as inactive precursors that
      must undergo post-translational proteolysis in order to mature and become active.
      In the current study, we address the challenge of sequence-based discovery of
      proteolytic sites in secreted proteins using machine learning. RESULTS: The
      results revealed that only half of the extracellular proteolytic sites are
      currently annotated, leaving over 3600 unannotated ones. Furthermore, we have
      found that only 6% of the unannotated sites are similar to known proteolytic
      sites, whereas the remaining 94% do not share significant similarity with any
      annotated proteolytic site. The computational challenges in these two cases are
      very different. While the precision in detecting the former group is close to
      perfect, only a mere 22% of the latter group were detected with a precision of
      80%. The applicability of the classifier is demonstrated through members of the
      FGF family, in which we verified the conservation of physiologically-relevant
      proteolytic sites in homologous proteins.

PMID- 18321888
TI  - Consensus generation and variant detection by Celera Assembler.
AB  - MOTIVATION: We present an algorithm to identify allelic variation given a Whole
      Genome Shotgun (WGS) assembly of haploid sequences, and to produce a set of
      haploid consensus sequences rather than a single consensus sequence. Existing WGS
      assemblers take a column-by-column approach to consensus generation, and produce
      a single consensus sequence which can be inconsistent with the underlying haploid
      alleles, and inconsistent with any of the aligned sequence reads. Our new
      algorithm uses a dynamic windowing approach. It detects alleles by simultaneously
      processing the portions of aligned reads spanning a region of sequence variation,
      assigns reads to their respective alleles, phases adjacent variant alleles and
      generates a consensus sequence corresponding to each confirmed allele. This
      algorithm was used to produce the first diploid genome sequence of an individual
      human. It can also be applied to assemblies of multiple diploid individuals and
      hybrid assemblies of multiple haploid organisms. RESULTS: Being applied to the
      individual human genome assembly, the new algorithm detects exactly two confirmed
      alleles and reports two consensus sequences in 98.98% of the total number
      2,033311 detected regions of sequence variation. In 33,269 out of 460,373
      detected regions of size >1 bp, it fixes the constructed errors of a mosaic
      haploid representation of a diploid locus as produced by the original Celera
      Assembler consensus algorithm. Using an optimized procedure calibrated against 1
      506 344 known SNPs, it detects 438 814 new heterozygous SNPs with false positive
      rate 12%. AVAILABILITY: The open source code is available at: http://wgs
      assembler.cvs.sourceforge.net/wgs-assembler/

PMID- 18321889
TI  - Malaria overdiagnosis: is patient pressure the problem?
AB  - OBJECTIVE: In Africa antimalarials are often prescribed when malaria is unlikely,
      a problem that is becoming critical as more expensive antimalarials replace
      established drugs. However, little is known about what drives the overuse of
      antimalarials. We conducted this study to explore to what extent current
      prescribing behaviour in hospitals is driven by patient demand. METHODS:
      Consultations were observed followed by exit interviews with patients or
      caretakers. Five district hospitals where microscopy was routinely available were
      selected in areas of low (n = 3) and high (n = 2) malaria transmission in north
      eastern Tanzania. All outpatient consultations during the study period were
      observed (n = 669). Those sent for a malaria blood slide or treated with
      antimalarials presumptively were interviewed (n = 326). At the end of the study,
      clinicians were interviewed for their opinions on the use of antimalarials.
      FINDINGS: Patients were not observed to demand antimalarials from clinicians, but
      occasionally asked for a malaria slide. Patient satisfaction on exit was similar
      between those prescribed antimalarials and those not prescribed antimalarials,
      but more patients or carers expressed satisfaction when the patient had been
      tested than when not. Clinicians rarely reported perceiving patient demand for
      antimalarials and asserted that such demand for medication would not affect their
      prescribing behaviour. CONCLUSIONS: Patient demand was not found to be driving
      the over-prescription of antimalarials found in the hospitals in our setting. To
      the contrary, the involvement of patients may provide an opportunity to improve
      prescribing practice if their expectations for testing and treatment in line with
      test results can be effectively communicated to clinicians.

PMID- 18321890
TI  - A case of lateral pelvic lymph node recurrence after TME for submucosal rectal
      carcinoma successfully treated by lymph node dissection with en bloc resection of
      the internal iliac vessels.
AB  - In Japan, lateral lymph node dissection (LLND) is generally performed for the
      treatment of T3-4 lower rectal carcinoma, and not for T1 lower rectal carcinoma,
      because of a low positive rate in patients with T1 lesion. We experienced a rare
      case of lateral pelvic lymph node recurrence after total mesorectal resection for
      T1 lower rectal carcinoma, successfully treated by LLND with en bloc resection of
      the internal iliac vessels. There is no guideline for the treatment of patients
      with isolated lateral lymph node recurrence; however, surgery should be
      considered for such patients.

PMID- 18321891
TI  - Survival of metastatic germ cell cancer patients assessed by international germ
      cell consensus classification in Japan.
AB  - BACKGROUND: As a risk classification system of metastatic germ cell tumors, the
      International Germ Cell Consensus (IGCC) classification was proposed in 1997 and
      has received broad approval. Since the IGCC classification was based on patients
      treated between 1975 and 1990, we aimed to investigate whether survival has
      improved for more recently treated Japanese patients. METHODS: We analyzed 296
      patients with metastatic germ cell tumors treated at seven hospitals in Japan
      between 1990 and 2001. These cases are classified as good, intermediate or poor
      prognosis groups by the IGCC classification. The 5-year progression-free and the
      5-year overall survivals were calculated for each prognosis group. RESULTS: The
      median follow-up period of all patients was 53 months. In 227 non-seminomatous
      germ cell tumor cases, the 5-year progression-free survival (95% confidence
      interval) for good (n = 55), intermediate (n = 106) and poor (n = 66) prognosis
      was 96% (91-100), 71% (62-80) and 52% (39-65) (P < 0.001), respectively. The 5
      year overall survival was 94% (88-100), 81% (73-89) and 61% (49-73) (P < 0.001),
      respectively. In 69 seminoma cases, the 5-year progression-free survival for good
      (n = 64) and intermediate (n = 5) prognosis was 78% (67-89) and 80% (45-100) (P =
      0.98), respectively. The 5-year overall survival was 90% (82-99) and 80% (45-100)
      (P = 0.49), respectively. CONCLUSIONS: There was a trend of increase in survival
      for any risk groups and, in particular, large increase in survival for patients
      with a poor prognosis. This increase is most likely attributed to more effective
      chemotherapy regimens and more extensive care in the experienced institutes.

PMID- 18321892
TI  - Fertility and pregnancy outcomes following uterine devascularization for severe
      postpartum haemorrhage.
AB  - BACKGROUND: To evaluate the fertility and pregnancy outcomes following uterine
      devascularization for postpartum haemorrhage (PPH). METHODS: All patients who
      required uterine devascularization, i.e. bilateral uterine artery ligation (Group
      A), and either bilateral utero-ovarian ligament (Group B) or suspensory ligament
      of ovary ligation (Group C) in cases of persistent haemorrhage, for PPH with no
      concomitant procedures from December 1997 to March 2004 were included. Data were
      retrieved from medical files and telephone interviews. RESULTS: Data were
      available for 32 of the 40 (80%) patients included in the study. All patients but
      4 had a return to normal menses. Postpartum amenorrhea was secondary to ovarian
      failure in two cases, and synechiae or necrotic uterus each in one case. These
      four patients belonged to Group C, whereas no adverse events were observed in
      groups A and B. Thirteen patients had 16 pregnancies with 13 term deliveries, 1
      ectopic pregnancy and 2 abortions. Clinical course of the 13 complete gestations
      were uneventful but PPH recurred in 4 (31%) due to placenta accreta in three
      cases. CONCLUSIONS: Uterine artery ligation, whether or not associated with utero
      ovarian ligament ligation, for PPH does not appear to compromise the patients'
      subsequent fertility and obstetrical outcome.

PMID- 18321893
TI  - ESHRE Task Force on Ethics and Law 14: equity of access to assisted reproductive
      technology.
AB  - Justice and access are among the most urgent questions for medically assisted
      reproduction. This paper analyses this question not only for people suffering
      from infertility, but also for people who need assistance to prevent the birth of
      a child with a specific genetic disorder. Based on the impact of not being able
      to have a child on the quality of life of a person, the position is defended that
      infertility treatment should be at least partially reimbursed. Simultaneously,
      the medical professionals have an obligation towards their patients and the
      health care system to bring down the costs as far as reasonably possible.

PMID- 18321894
TI  - Higher incidence of linked malformations in siblings of Mayer-Rokitansky-Kuster
      Hauser-syndrome patients.
AB  - BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a malformation of
      the female genital tract (vaginal aplasia, rudimentary uterus, normal fallopian
      tubes and high ovaries). The incidence is one in 4000 female newborns. The aim of
      the present study was to record genital and associated malformations among
      siblings and relatives of MRKH patients in order to draw possible conclusions
      regarding the etiology of the syndrome: heredity (dominant versus recessive) or
      spontaneous malformation. METHODS: Using a standardized questionnaire, affected
      MRKH patients were asked about other cases of MRKH and/or associated
      malformations among siblings and relatives. RESULTS: No other cases of MRKH
      syndrome had occurred among the siblings or relatives of 73 MRKH patients;
      however, 13 associated malformations were recorded among a total of 103 siblings.
      Musculoskeletal malformations were markedly increased (3.27 times higher) in
      comparison with the prevalence of congenital malformations among newborns in the
      normal population. CONCLUSIONS: This study shows that dominant inheritance cannot
      play a role in the etiology of MRKH syndrome, as no further cases of MRKH
      syndrome occurred among any of the siblings. The study provides support for the
      view that the syndrome has a multifactorial pathogenesis. Siblings/relatives of
      MRKH patients should be examined for associated musculoskeletal/urogenital
      malformations.

PMID- 18321895
TI  - Experience of famine and bone health in post-menopausal women.

PMID- 18321896
TI  - Is sublingual immunotherapy "ready for prime time"?

PMID- 18321897
TI  - There is no "cap" on the importance of community-acquired pneumonia in the ICU.

PMID- 18321898
TI  - Estimation of mean pulmonary artery pressure: simpler than expected.

PMID- 18321899
TI  - Staging of lung cancer.

PMID- 18321900
TI  - Determination of therapeutic continuous positive airway pressure for obstructive
      sleep apnea using automatic titration: promises not fulfilled.

PMID- 18321902
TI  - Automatic titration and calculation by predictive equations for the determination
      of therapeutic continuous positive airway pressure for obstructive sleep apnea.
AB  - BACKGROUND: It is unknown to what extent therapeutic continuous positive airway
      pressure (CPAP) levels obtained by various methods for the treatment of
      obstructive sleep apnea syndrome (OSAS) differ. This study aimed to explore the
      relationships among pressures titrated by an automatic CPAP (APAP) device and
      those calculated using different predictive equations, and to compare different
      ranges of calculated pressures with pressure values titrated by APAP. METHODS: In
      140 OSAS patients, the 95th percentile pressure delivered by an APAP device
      (AutoSet T; ResMed; Sydney, NSW, Australia) during polysomnography, and pressures
      calculated by three equations (equation 1, Hoffstein and Miljetig [1994];
      equation 2, Series et al [2000]; and equation 3, Stradling et al [2004]) were
      compared. RESULTS: Titrated and calculated pressures were weakly correlated.
      Significant differences were found between the mean (+/- SD) pressures (11.1 +/-
      1.6, 8.3 +/- 1.8, 10.5 +/- 1.6, and 10.3 +/- 1.3 cm H(2)O, respectively) for 95th
      percentile APAP, and pressures calculated by equations 1, 2, and 3, except
      between values calculated by equations 2and 3. Differences between the calculated
      and APAP-derived pressures were negative for the low calculated values, and were
      progressively attenuated, or became positive, for the high values. The
      differences were smallest for calculated pressures from 11 to > 13 cm H(2)O,
      which were represented to a greater extent among the values calculated by
      equations 2 and 3 than by those calculated by equation 1. CONCLUSIONS:
      Considerably different therapeutic CPAP levels may be determined using various
      methods. The differences between the calculated and APAP-derived pressures are
      largest for calculated values of < 9 or > 15 cm H(2)O. The clinical consequences
      of these findings deserve further evaluation. Caution is still required before
      treating OSAS patients with calculated pressures.

PMID- 18321903
TI  - Medication and dosage considerations in the prophylaxis and treatment of high
      altitude illness.
AB  - With increasing numbers of people traveling to high altitude for work or
      pleasure, there is a reasonable chance that many of these travelers have
      preexisting medical conditions or are receiving various medications at the time
      of their sojourn. As with all travelers to high altitude, they are at risk for
      altitude illnesses such as acute mountain sickness, high-altitude cerebral edema,
      and high-altitude pulmonary edema. While there are clear recommendations for
      pharmacologic measures to prevent or treat these illnesses, these recommendations
      are oriented toward healthy individuals and do not take into account the presence
      of preexisting medical conditions. In this review, we consider how the choice and
      dose of the medications used in the management of altitude illness-acetazolamide,
      dexamethasone, nifedipine, tadalafil, sildenafil, and salmeterol-are affected by
      a patient's underlying medical conditions. We discuss the indications and current
      dosing recommendations for individuals without underlying disease, and then
      consider how drug selection or dosing regimens will be affected by the presence
      of renal insufficiency, hepatic insufficiency, other important medical
      conditions, and the potential for serious drug interactions. We include comments
      about interactions with antimalarial medications and antibiotics used in the
      treatment of traveler's diarrhea, as well as the safety of use during pregnancy.
      By giving these issues adequate consideration, clinicians can increase the
      chances that properly evaluated patients with underlying medical conditions will
      enjoy a safe trip to high altitude.

PMID- 18321904
TI  - Contemporary management of acute exacerbations of COPD: a systematic review and
      metaanalysis.
AB  - BACKGROUND: Systemic corticosteroids, antibiotics, and noninvasive positive
      pressure ventilation (NPPV) are recommended for patients with acute exacerbation
      of COPD. However, their clinical benefits in various settings are uncertain. We
      undertook a systematic review and metaanalysis to systematically evaluate the
      effectiveness of these therapies. METHODS: MEDLINE and EMBASE were searched to
      identify relevant randomized controlled clinical trials published from January
      1968 to November 2006. We identified additional studies by searching
      bibliographies of retrieved articles. RESULTS: Compared with placebo, systemic
      corticosteroids reduced treatment failure by 46% (95% confidence interval [CI],
      0.41 to 0.71), length of hospital stay by 1.4 days (95% CI, 0.7 to 2.2), and
      improved FEV(1) by 0.13 L after 3 days of therapy (95% CI, 0.04 to 0.21).
      Meanwhile, the risk of hyperglycemia significantly increased (relative risk,
      5.88; 95% CI, 2.40 to 14.41). Compared with placebo, antibiotics reduced
      treatment failure by 46% (95% CI, 0.32 to 0.92) and in-hospital mortality by 78%
      (95% CI, 0.08 to 0.62). Compared with standard therapy, NPPV reduced the risk of
      intubation by 65% (95% CI, 0.26 to 0.47), in-hospital mortality by 55% (95% CI,
      0.30 to 0.66), and the length of hospitalization by 1.9 days (95% CI, 0.0 to
      3.9). CONCLUSIONS: For acute COPD exacerbations, systemic corticosteroids are
      effective in reducing treatment failures, while antibiotics reduce mortality and
      treatment failures in those requiring hospitalization and NPPV reduces the risk
      of intubation and in-hospital mortality, especially in those who demonstrate
      respiratory acidosis.

PMID- 18321905
TI  - Meeting physicians' responsibilities in providing end-of-life care.
AB  - Despite many clinical examples of exemplary end-of-life care, a number of studies
      highlight significant shortcomings in the quality of end-of-life care that the
      majority of patients receive. In part, this stems from inconsistencies in
      training and supporting clinicians in delivering end-of-life care. This review
      describes the responsibilities of pulmonary and critical care physicians in
      providing end-of-life care to patients and their families. While many
      responsibilities are common to all physicians who care for patients with life
      limiting illness, some issues are particularly relevant to pulmonary and critical
      care physicians. These issues include prognostication and decision making about
      goals of care, challenges and approaches to communicating with patients and their
      family, the role of interdisciplinary collaboration, principles and practice of
      withholding and withdrawing life-sustaining measures, and cultural competency in
      end-of-life care.

PMID- 18321906
TI  - A case of precocious emphysema and lung cancer in a woman with a history of
      hypocomplementemic urticarial vasculitis.
AB  - Severe emphysema developed in a white woman with a 26-pack-year history of
      tobacco use. Serum alpha(1)-antitrypsin levels were normal. A history of
      autoimmune hemolytic anemia, angioedema, low complement, and recurrent urticaria
      prompted an immunologic workup that ultimately led to a diagnosis of
      hypocomplementemic urticarial vasculitis syndrome. Treatment with oral prednisone
      and inhaled bronchodilators improved symptoms, but 4 months after diagnosis non
      small cell lung cancer was discovered and she ultimately died. Hypocomplementemic
      urticarial vasculitis is an uncommon cause of precocious emphysema and has not
      previously been reported in a patient with bronchogenic carcinoma.

PMID- 18321907
TI  - Dramatic functional improvement following bariatric surgery in a patient with
      pulmonary arterial hypertension and morbid obesity.
AB  - Pulmonary arterial hypertension (PAH) and morbid obesity both dramatically impair
      functional capacity. New therapies have emerged for both conditions, including
      pharmaceutical agents for the former and bariatric surgery for the latter. The
      presence of both conditions simultaneously, however, may limit the applicability
      and effectiveness of these therapies. We report a case of a morbidly obese
      patient with severe PAH and functional impairment. A three-drug combination
      regimen consisting of oral bosentan and sildenafil, and inhaled iloprost produced
      sufficient hemodynamic improvement to allow for the performance of bariatric
      surgery. Over the subsequent 7 months, body weight, oxygen requirement,
      functional class, and 6-min walk distance all improved dramatically despite the
      persistence of PAH. While such surgery is typically denied to patients with PAH,
      we suggest that aggressive medical therapy for patients with PAH may allow for
      its safe performance, and that the clinical improvement resulting from the
      subsequent weight loss may be quite dramatic.

PMID- 18321908
TI  - Obstructive sleep apnea: implications for cardiac and vascular disease.

PMID- 18321909
TI  - A 64-year-old man with joint swelling and an abnormal chest radiograph.

PMID- 18321910
TI  - A 27-year-old woman with a swollen uvula, chest pain, and elevated creatinine
      phosphokinase levels.

PMID- 18321911
TI  - A 46-year-old man with dyspnea, Dysphagia, and pulmonary hypertension.

PMID- 18321912
TI  - A 40-year-old man with neutropenic fever and lobar consolidation.

PMID- 18321913
TI  - Wheezing and exertional dyspnea in a 25-year-old mountaineer.

PMID- 18321914
TI  - Studying a film on the treatment of burns.

PMID- 18321915
TI  - Great data, but how do we use it?

PMID- 18321916
TI  - Evaluation of ICU admission criteria and diagnostic methods for patients with
      severe community-acquired pneumonia: current practice survey.

PMID- 18321917
TI  - Premature atrial contraction as an etiology for cough.

PMID- 18321918
TI  - Electromagnetic navigation diagnostic bronchoscopy and transbronchial biopsy.

PMID- 18321919
TI  - Stenting for tracheobronchomalacia: treating images?

PMID- 18321920
TI  - Grading recommendations: a matter of interpretation.

PMID- 18321921
TI  - Reference values for exhaled nitric oxide in the general population.

PMID- 18321923
TI  - Regulatory T cells, allergic diseases, and cancer.

PMID- 18321924
TI  - Unilateral vestibular failure suppresses cortical visual motion processing.
AB  - Patients with unilateral vestibular failure (UVF) experience oscillopsia
      (apparent motion of the visual scene) during rapid head movements due to
      increased retinal slip caused by vestibulo-ocular reflex impairment. Oscillopsia
      is always smaller than the net retinal slip and decreases over time in patients
      with acquired vestibular loss; this correlates with increased thresholds for
      visual motion detection and increased tolerance to retinal slip. We investigated
      the underlying cortical adaptive processes using visual motion stimulation during
      blood oxygen level-dependent (BOLD) fMRI. Optokinetic nystagmus was elicited in
      seven patients with right-sided and seven patients with left-sided unilateral
      vestibular neurectomy and in seven age- and gender-matched healthy controls.
      Patients showed diminished activation of bilateral visual cortex areas (including
      the motion-sensitive area MT/V5, cuneus, middle occipital, fusiform and lingual
      areas) and ocular motor regions compared to their controls during visual motion
      stimulation. Concurrent BOLD signal decreases of temporo-parietal and insular
      multisensory cortical areas occurred in controls and patients. The diminished
      activation of visual motion processing areas plausibly reflects an adaptive
      mechanism that suppresses distressing oscillopsia in patients with UVF and
      thereby stabilizes the perceived visual surroundings. This study provides for the
      first time neuroimaging evidence of suppressed cortical visual motion processing
      in patients with vestibulopathy.

PMID- 18321925
TI  - REEP1 mutation spectrum and genotype/phenotype correlation in hereditary spastic
      paraplegia type 31.
AB  - Mutations in the receptor expression enhancing protein 1 (REEP1) have recently
      been reported to cause autosomal dominant hereditary spastic paraplegia (HSP)
      type SPG31. In a large collaborative effort, we screened a sample of 535
      unrelated HSP patients for REEP1 mutations and copy number variations. We
      identified 13 novel and 2 known REEP1 mutations in 16 familial and sporadic
      patients by direct sequencing analysis. Twelve out of 16 mutations were small
      insertions, deletions or splice site mutations. These changes would result in
      shifts of the open-reading-frame followed by premature termination of translation
      and haploinsufficiency. Interestingly, we identified two disease associated
      variations in the 3'-UTR of REEP1 that fell into highly conserved micro RNA
      binding sites. Copy number variation analysis in a subset of 133 HSP index
      patients revealed a large duplication of REEP1 that involved exons 2-7 in an
      Irish family. Clinically most SPG31 patients present with a pure spastic
      paraplegia; rare complicating features were restricted to symptoms or signs of
      peripheral nerve involvement. Interestingly, the distribution of age at onset
      suggested a bimodal pattern with the appearance of initial symptoms of disease
      either before the age of 20 years or after the age of 30 years. The overall
      mutation rate in our clinically heterogeneous sample was 3.0%; however, in the
      sub-sample of pure HSP REEP1 mutations accounted for 8.2% of all patients. These
      results firmly establish REEP1 as a relatively frequent autosomal dominant HSP
      gene for which genetic testing is warranted. We also establish haploinsufficiency
      as the main molecular genetic mechanism in SPG31, which should initiate and guide
      functional studies on REEP1 with a focus on loss-of-function mechanisms. Our
      results should be valid as a reference for mutation frequency, spectrum of REEP1
      mutations, and clinical phenotypes associated with SPG31.

PMID- 18321926
TI  - Neutrophil degranulation mediates severe lung damage triggered by streptococcal
      M1 protein.
AB  - Streptococcus pyogenes of the M1 serotype can cause streptococcal toxic shock
      syndrome commonly associated with acute lung injury. The aim of the present study
      was to investigate the role of neutrophils and their secretion products in M1
      protein-induced lung damage. The degranulation of neutrophils by M1 protein was
      studied in whole blood using marker analysis for individual granule subsets. In
      mice, M1 protein was injected intravenously and the lung damage was assessed by
      histology, electron microscopy, cell count in bronchoalveolar lavage fluid and
      analysis of lung vascular permeability. Comparisons were made in mice with intact
      white blood count, neutropenic mice and neutropenic mice injected with the
      secretion of activated neutrophils. In whole blood, M1 protein forms complexes
      with fibrinogen that bind to beta(2)-integrins on the neutrophil surface,
      resulting in degranulation of all four subsets of neutrophil granules.
      Intravenous injection of M1 protein into mice induced neutrophil accumulation in
      the lung, increase in vascular permeability and acute lung damage. Depletion of
      neutrophils from the circulation completely abrogated lung injury and vascular
      leakage. Interestingly, the lung damage was restored by injecting neutrophil
      secretion. The present data suggest that neutrophil granule proteins are directly
      responsible for lung damage induced by the streptococcal M1 protein.

PMID- 18321927
TI  - Identification of transcripts overexpressed during airway epithelium
      differentiation.
AB  - Human airway epithelium, the defence at the forefront of protecting the
      respiratory tract, evacuates inhaled particles by a permanent beating of
      epithelial cell cilia. When deficient, this organelle causes primary ciliary
      dyskinesia, and, despite numerous studies, data regarding ciliated cell gene
      expression remain incomplete. The aim of the present study was to identify genes
      specifically expressed in human ciliated respiratory cells via transcriptional
      analysis. The transcriptome of dedifferentiated epithelial cells was subtracted
      from that of fully redifferentiated cells using complementary DNA
      representational difference analysis. In order to validate the results, gene
      overexpression in ciliated cells was confirmed by real-time PCR, and by comparing
      the present list of genes overexpressed in ciliated cells to lists obtained in
      previous studies. A total of 53 known and 12 unknown genes overexpressed in
      ciliated cells were identified. The majority (66%) of known genes had never
      previously been reported as being involved in ciliogenesis, and the unknown genes
      represent hypothetical novel transcript isoforms or new genes not yet reported in
      databases. Finally, several genes identified here were located in genomic regions
      involved in primary ciliary dyskinesia by linkage analysis. In conclusion, the
      present study revealed sequences of new cilia-related genes, new transcript
      isoforms and novel genes which should be further characterised to aid
      understanding of their function(s) and their probable disorder-related
      involvement.

PMID- 18321928
TI  - TGF-beta receptor II in epithelia versus mesenchyme plays distinct roles in the
      developing lung.
AB  - Transforming growth factor (TGF)-beta signalling plays important roles in
      regulating lung development. However, the specific regulatory functions of TGF
      beta signalling in developing lung epithelial versus mesenchymal cells are still
      unknown. By immunostaining, the expression pattern of the TGF-beta type II
      receptor (TbetaRII) was first determined in the developing mouse lung. The
      functions of TbetaRII in developing lung were then determined by conditionally
      knocking out TbetaRII in the lung epithelium of floxed-TbetaRII/surfactant
      protein C-reverse tetracycline transactivator/TetO-Cre mice versus mesenchyme of
      floxed-TbetaRII/Dermo1-Cre mice. TbetaRII was expressed only in distal airway
      epithelium at early gestation (embryonic day (E)11.5), but in both airway
      epithelium and mesenchyme from mid-gestation (E14.5) to post-natal day 14.
      Abrogation of TbetaRII in mouse lung epithelium resulted in retardation of post
      natal lung alveolarisation, with markedly decreased type I alveolar epithelial
      cells, while no abnormality in prenatal lung development was observed. In
      contrast, blockade of TbetaRII in mesoderm-derived tissues, including lung
      mesenchyme, resulted in mildly abnormal lung branching and reduced cell
      proliferation after mid-gestation, accompanied by multiple defects in other
      organs, including diaphragmatic hernia. The primary lung branching defect was
      verified in embryonic lung explant culture. The novel findings of the present
      study suggest that transforming growth factor-beta type II receptor-mediated
      transforming growth factor-beta signalling plays distinct roles in lung
      epithelium versus mesenchyme to differentially control specific stages of lung
      development.

PMID- 18321929
TI  - Sex differences in physiological progression of idiopathic pulmonary fibrosis.
AB  - In idiopathic pulmonary fibrosis, incidence is higher in males, and females may
      have better survival. The aim of the present study was to determine whether the
      rate of increase in desaturation during serial 6-min walk testing would be
      greater, and survival worse, for males versus females. Serial changes in the
      percentage of maximum desaturation area (DA) over 1 yr were estimated using mixed
      models in 215 patients. DA was defined as the total area above the curve created
      using desaturation percentage values observed during each minute of the 6-min
      walk test. Multivariate Cox regression assessed survival differences. Adjusting
      for baseline DA, 6-min walk distance, change in 6-min walk distance over time and
      smoking history, the percentage of maximum DA increased by an average of 2.83 and
      1.37% per month for males and females, respectively. Females demonstrated better
      survival overall, which was more pronounced in patients who did not desaturate
      below 88% on ambulation at baseline and after additionally adjusting for 6-month
      relative changes in DA and forced vital capacity. These data suggest that
      differences in disease progression contribute to, but do not completely explain,
      better survival of females with idiopathic pulmonary fibrosis.

PMID- 18321930
TI  - Chest wall volume regulation during exercise in COPD patients with GOLD stages II
      to IV.
AB  - The present study investigated how end-expiratory ribcage and abdominal volume
      regulation during exercise is related to the degree of dynamic chest wall
      hyperinflation in patients with different spirometric severity of chronic
      obstructive pulmonary disease (COPD) based on the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) classification. In total, 42 COPD patients and 11
      age-matched healthy subjects were studied during a ramp-incremental cycling test
      to the limit of tolerance (W(peak)). Volume variations of the chest wall (at end
      expiration (EEV(cw)) and end inspiration) and its compartments (ribcage (V(rc))
      and abdominal (V(ab))) were computed by optoelectronic plethysmography. At
      W(peak), only patients in GOLD stages III and IV exhibited a significant increase
      in EEV(cw) (increase of 454+/-509 and 562+/-363 mL, respectively). These patients
      did not significantly reduce end-expiratory V(ab), whereas patients in GOLD stage
      II resembled healthy subjects with significantly reduced end-expiratory V(ab)
      (decrease of 287+/-350 mL). In patients, the greater the increase in EEV(cw) at
      W(peak), the smaller the reductions in end-expiratory V(ab) and the greater the
      increase in end-expiratory V(rc). In chronic obstructive pulmonary disease
      patients with different spirometric disease severity, greater degrees of exercise
      induced dynamic chest wall hyperinflation were accompanied by lower degrees of
      end-expiratory abdominal volume displacement and larger increases in end
      expiratory ribcage volume.

PMID- 18321931
TI  - Extracellular matrix components and regulators in the airway smooth muscle in
      asthma.
AB  - There is an intimate relationship between the extracellular matrix (ECM) and
      smooth muscle cells within the airways. Few studies have comprehensively assessed
      the composition of different ECM components and its regulators within the airway
      smooth muscle (ASM) in asthma. With the aid of image analysis, the fractional
      areas of total collagen and elastic fibres were quantified within the ASM of 35
      subjects with fatal asthma (FA) and compared with 10 nonfatal asthma (NFA)
      patients and 22 nonasthmatic control cases. Expression of collagen I and III,
      fibronectin, versican, matrix metalloproteinase (MMP)-1, -2, -9 and -12 and
      tissue inhibitor of metalloproteinase-1 and -2 was quantified within the ASM in
      22 FA and 10 control cases. In the large airways of FA cases, the fractional area
      of elastic fibres within the ASM was increased compared with NFA and controls.
      Similarly, fibronectin, MMP-9 and MMP-12 were increased within the ASM in large
      airways of FA cases compared with controls. Elastic fibres were increased in
      small airways in FA only in comparison with NFA cases. There is altered
      extracellular matrix composition and a degradative environment within the airway
      smooth muscle in fatal asthma patients, which may have important consequences for
      the mechanical and synthetic functions of airway smooth muscle.

PMID- 18321932
TI  - Performance of ventilators for noninvasive positive-pressure ventilation in
      children.
AB  - The aim of the present study was to evaluate the performance characteristics of
      all the ventilators proposed for home noninvasive positive-pressure ventilation
      in children in France. The ventilators (one volume-targeted, 12 pressure-targeted
      and four dual) were evaluated on a bench which simulated six different paediatric
      ventilatory patterns. For each ventilator, the quality of the inspiratory and
      expiratory trigger and the ability to reach and maintain the preset pressures and
      volumes were evaluated with the six patient profiles. The performance of the
      ventilators showed great variability, and depended upon the type of trigger (flow
      or pressure), type of circuit and patient profile. Differences were observed
      between the preset and measured airway pressure and between the tidal volume
      measured by the ventilator and on the bench. Leaks were associated with an
      inability to detect the patient's inspiratory effort or autotriggering. No single
      ventilator was able to adequately ventilate the six paediatric profiles. Only a
      few ventilators were able to ventilate the profiles simulating the youngest
      patients. A systematic paediatric bench evaluation is recommended for every
      ventilator proposed for home ventilation, in order to detect any dysfunction and
      guide the choice of the appropriate ventilator for a specific patient.

PMID- 18321933
TI  - The association between serum osmolality and lung function among adults.
AB  - The extensive pulmonary vasculature results in the lungs being intimately exposed
      to circulating blood. As increased serum osmolality may be associated with an
      increase in pro-inflammatory activity, this has the potential to result in damage
      to the lungs and reduced lung function. The objective of the present study was to
      test the hypothesis that increased serum osmolality is associated with a lower
      forced expiratory volume in one second (FEV(1)) and forced vital capacity (FVC).
      The present study was a cross-sectional study of 10,602 participants in the Third
      National Health and Nutrition Examination Survey aged > or = 17 yrs for whom
      there were adequate data on all outcomes and exposures. After adjustment for age,
      smoking and other confounding factors, increased serum osmolality was inversely
      associated with both FEV(1) and FVC. An increase of 1 sd in serum osmolality was
      associated with a decrease in both FEV(1) of 19.8 mL and FVC of 35.3 mL. The
      constituent assays demonstrated a complex relationship with both FEV(1) and FVC.
      Increased serum osmolality was associated with decreased forced expiratory volume
      in one second and forced vital capacity. If causal, this may have implications
      for the understanding of the processes that are involved in the pathophysiology
      of decline in lung function.

PMID- 18321934
TI  - Clock gene dysfunction in patients with obstructive sleep apnoea syndrome.
AB  - Clock genes regulate mammalian circadian rhythms, and dysfunction of clock genes
      can contribute to various disorders. To investigate whether obstructive sleep
      apnoea syndrome (OSAS) influences clock gene function, the present authors
      examined Period1 (Per1) mRNA expression in vitro and in vivo. In eight healthy
      subjects and eight OSAS patients, plasma noradrenaline, serum interleukin (IL)-6,
      high-sensitivity C-reactive protein (hsCRP) and Per1 mRNA expression in
      peripheral whole blood were measured. Expression of Per1 mRNA in cultured cells
      was examined under IL-6 or noradrenaline stimulation in vitro. After
      noradrenaline was administered to mice in vivo, Per1 mRNA expression in the brain
      was examined. The concentrations of serum IL-6, hsCRP and plasma noradrenaline
      were elevated in OSAS patients, but improved by continuous positive airway
      pressure (CPAP) therapy. Per1 mRNA expression in the peripheral blood
      significantly decreased at 02:00 h by CPAP in OSAS patients. Stimulation with IL
      6 did not directly induce Per1 mRNA in vitro. Administration of noradrenaline
      induced Per1 mRNA in the cerebral cortex of mice in vivo. The current study
      revealed that obstructive sleep apnoea syndrome caused clock gene dysfunction,
      and continuous positive airway pressure helped to improve it. Sympathetic
      activation and elevation of the plasma noradrenaline concentration in obstructive
      sleep apnoea syndrome may be one of the factors involved in disorders of Period1
      mRNA expression.

PMID- 18321935
TI  - Leukotriene B4: early mediator of atherosclerosis in obstructive sleep apnoea?
AB  - Severity of oxygen desaturation is predictive of early atherosclerosis in
      obstructive sleep apnoea (OSA). Leukotriene (LT)B(4) is a lipid mediator involved
      in atherogenesis. In 40 non-obese OSA patients, free of a cardiovascular history,
      and 20 healthy volunteers, the following were evaluated: 1) LTB(4) production by
      polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the
      relationships between LTB(4) production and both OSA severity and infraclinical
      atherosclerosis markers. The effect of continuous positive airway pressure (CPAP)
      on LTB(4) production was also studied. An overnight sleep study was followed by
      first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order
      to induce LTB(4) production, which was measured by liquid chromatography-tandem
      mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were
      measured in subset groups of 28 OSA patients and 11 controls. LTB(4) production
      was increased in OSA patients compared with controls. LTB(4) levels correlated
      with the mean and minimal arterial oxygen saturation (S(a,O(2))). LTB(4)
      production correlated with luminal diameter data in patients with a mean
      S(a,O(2)) of < or = 94% but not with IMT. Lastly, CPAP significantly reduced
      LTB(4) production by 50%. Leukotriene B(4) production is increased in obstructive
      sleep apnoea in relation to oxygen desaturation. Leukotriene B(4) could promote
      early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea
      patients.

PMID- 18321936
TI  - Effects of inhaled human insulin on airway lining fluid composition in adults
      with diabetes.
AB  - Inhaled human insulin (Exubera (human insulin of rDNA origin) Inhalation Powder)
      causes small, early and reversible changes in pulmonary function in subjects with
      diabetes mellitus. The present study assessed whether changes occur in cellular
      and soluble constituents of airway lining fluid consistent with inflammation as a
      possible cause for Exubera-associated lung function alterations. Two 31-week,
      open-label, sequential design phase 2 studies were conducted, one with 20
      subjects with type 1 and one with 24 subjects with type 2 diabetes. After run-in,
      all subjects received subcutaneous insulin for 12 weeks, followed after 1 week by
      12 weeks of Exubera. Bronchoalveolar lavage fluid cell counts and protein
      constituents were determined at baseline, after 12 weeks of subcutaneous insulin
      and after 12 weeks of Exubera. Baseline cellular and soluble constituents of
      lavage fluid were similar to those reported for nondiabetic adults. Exubera
      produced no consistent clinically or statistically significant changes in total
      or differential lavage fluid cell counts or protein concentrations, even though
      Exubera-associated changes in pulmonary function are known to be fully manifest
      within 12 weeks. Therefore, 12 weeks of Exubera treatment is not associated with
      evidence of pulmonary inflammation. The treatment effects on lung function
      observed in Exubera trials are not caused by lung inflammation.

PMID- 18321937
TI  - Modulation of bleomycin-induced lung fibrosis by serotonin receptor antagonists
      in mice.
AB  - Serotonin (5-hydroxytryptamine; 5-HT) is known to increase proliferation and
      collagen synthesis by fibroblasts. Two receptor subtypes, 5-HT2A and 5-HT2B, have
      been shown to play the most important roles in the lung. In the present study,
      the role of serotonin in lung fibrosis was investigated using the bleomycin mouse
      model. Serotonin concentrations in lung homogenates increased significantly over
      the time course of bleomycin-induced fibrosis, with a maximum at day seven. The
      expression of serotonin receptors 5-HT2A and 5-HT2B increased in the lung after
      bleomycin treatment, as assessed by PCR, specific binding and
      immunohistochemistry. Blockage of 5-HT2A receptors by ketanserin and 5-HT2B
      receptors by SB215505 reduced bleomycin-induced lung fibrosis, as demonstrated by
      reduced lung collagen content and reduced procollagen 1 and procollagen 3 mRNA
      expression. Serotonin antagonists promoted an antifibrotic environment by
      decreasing the lung mRNA levels of transforming growth factor-beta1, connective
      growth factor and plasminogen activator inhibitor-1 mRNA, but had minimal effects
      on lung inflammation as assessed by bronchoalveolar lavage cytology analysis.
      Interestingly, the 5-HT2B receptor was strongly expressed by fibroblasts in the
      fibroblastic foci in human idiopathic pulmonary fibrosis samples. In conclusion,
      the present study showed involvement of serotonin in the pathophysiology of
      bleomycin-induced lung fibrosis in mice and identified it as a potential
      therapeutic target in lung fibrotic disorders.

PMID- 18321938
TI  - Relationship between depression and exacerbations in COPD.
AB  - Chronic obstructive pulmonary disease is associated with exacerbations. Some
      patients are prone to frequent exacerbations and these individuals have a worse
      quality of life, greater limitation of their daily activity and faster disease
      progression than patients with less frequent exacerbations. A prospective study
      in a well-characterised cohort was performed and it was assessed whether
      depression, as determined by the Centre for Epidemiologic Studies Depression
      Scale, was related to exacerbation frequency, systemic inflammation and various
      social factors. The associations of any increase in depressive symptoms at
      exacerbation were also investigated. Frequent exacerbators had a significantly
      higher median (interquartile range) baseline depression score than infrequent
      exacerbators (17.0 (7.0-25.0) and 12.0 (6.0-18.0), respectively). Depressed
      patients spend significantly less time outdoors and had significantly worse
      quality of life as measured by the St George's Respiratory Questionnaire.
      Depression increased significantly in patients from baseline to exacerbation
      (12.5 (5.0-19.0) and 19.5 (12.0-28.0) respectively). The present study is the
      first to show a relationship between depression and exacerbation frequency in
      patients with chronic obstructive pulmonary disease. The finding that frequent
      exacerbators are more depressed than infrequent exacerbators is relevant, as
      exacerbation frequency is an important outcome measure in chronic obstructive
      pulmonary disease.

PMID- 18321939
TI  - Diesel exhaust exposure enhances the ozone-induced airway inflammation in healthy
      humans.
AB  - Exposure to particulate matter and ozone cause adverse airway reactions.
      Individual pollutant effects are often addressed separately, despite coexisting
      in ambient air. The present investigation was performed to study the effects of
      sequential exposures to diesel exhaust (DE) and ozone on airway inflammation in
      human subjects. Healthy subjects underwent bronchoscopy with bronchoalveolar
      lavage (BAL) and bronchial wash (BW) sampling on two occasions. Once following a
      DE exposure (with 300 mug.m(-3) particles with a 50% cut-off aerodynamic diameter
      of 10 mum) with subsequent exposure to O(3) (0.2 ppm) 5 h later. The other
      bronchoscopy was performed after a filtered air exposure followed by an ozone
      exposure, using an identical protocol. Bronchoscopy was performed 24 h after the
      start of the initial exposure. Significant increases in neutrophil and macrophage
      numbers were found in BW after DE followed by ozone exposure versus air followed
      by ozone exposure. DE pre-exposure also raised eosinophil protein X levels in BAL
      compared with air. The present study indicates additive effects of diesel exhaust
      on the ozone-induced airway inflammation. Together with similar results from a
      recent study with sequential diesel exhaust and ozone exposures, the present data
      stress a need to consider the interaction and cumulative effects of different air
      pollutants.

PMID- 18321940
TI  - C-reactive protein, obesity, atopy and asthma symptoms in middle-aged adults.
AB  - Recent research has suggested an association between circulating C-reactive
      protein (CRP) and adult asthma, confined to those without evidence of allergic
      predisposition. The current authors investigated the role of smoking and obesity
      as possible explanations for this relationship. At 44-45 yrs of age, members of
      the British 1958 birth cohort participated in a biomedical survey involving the
      measurement of the following: CRP; the specific immunoglobulin E to grass, cat
      and dust mite; standing height; and weight. Information on asthma and related
      symptoms was collected by computer-aided interview when the subjects were 42 yrs
      of age. Complete data were available for a total of 6,490 subjects. CRP levels
      were positively correlated with the body mass index (BMI) and were found to be
      higher among females when compared with males, and higher among heavy smokers (>
      or = 20 cigarettes x day(-1)) when compared with never-smokers. After adjustment
      for sex and region, the odds ratios, comparing asthma prevalence in subjects
      above the fourth CRP quartile with subjects below the first quartile, were 1.85
      (95% confidence interval 1.15-2.99) for nonatopics and 0.94 (0.62-1.41) for
      atopics, changing to 1.36 (0.80-2.32) and 1.07 (0.67-1.69), respectively, when
      additionally adjusted for smoking and BMI. Any association between C-reactive
      protein and asthma prevalence confined to nonatopics may be due to confounding
      factors. Alternatively, it may reflect a more general association of C-reactive
      protein with smoking-related obstructive airways disease.

PMID- 18321941
TI  - Mycobacterium avium complex disease: prognostic implication of high-resolution
      computed tomography findings.
AB  - To evaluate the prognostic implications of computed tomography (CT) findings in
      assessing responses to treatment in Mycobacterium avium complex (MAC) pulmonary
      disease without underlying lung disease, high-resolution (HR)CT findings were
      correlated based on the results of sputum conversion after anti-MAC therapy. A
      total of 59 patients underwent HRCT before treatment and the therapeutic efficacy
      was evaluated by the results of sputum conversion. Atelectasis, cavities and
      pleural thickening on HRCT were significantly more frequent and extensive among
      patients in the sputum nonconverted group than among those in the converted
      group. Furthermore, bronchiectasis was also significantly more extensive among
      patients in the nonconverted group, even though there was no significant
      difference in frequency between these two groups. These results suggest that high
      resolution computed tomography findings are good predictors of response to
      treatment in Mycobacterium avium complex pulmonary disease.

PMID- 18321942
TI  - Incremental utility of real-time three-dimensional echocardiography in the
      diagnosis and preoperative assessment of cleft mitral valve in adults.
AB  - Cleft mitral valve is a rare congenital anomaly that may present in isolation or
      accompany other cardiac malformations. Our illustrative case series highlights
      the advantages of three-dimensional over conventional two-dimensional
      echocardiography in the diagnosis and morphologic assessment cleft mitral valve
      in adults.

PMID- 18321943
TI  - Guidelines on the management of common bile duct stones (CBDS).
AB  - The last 30 years have seen major developments in the management of gallstone
      related disease, which in the United States alone costs over 6 billion dollars
      per annum to treat. Endoscopic retrograde cholangiopancreatography (ERCP) has
      become a widely available and routine procedure, whilst open cholecystectomy has
      largely been replaced by a laparoscopic approach, which may or may not include
      laparoscopic exploration of the common bile duct (LCBDE). In addition, new
      imaging techniques such as magnetic resonance cholangiography (MR) and endoscopic
      ultrasound (EUS) offer the opportunity to accurately visualise the biliary system
      without instrumentation of the ducts. As a consequence clinicians are now faced
      with a number of potentially valid options for managing patients with suspected
      CBDS. It is with this in mind that the following guidelines have been written.

PMID- 18321944
TI  - Macrovascular disease and atherosclerosis in SSc.
AB  - Atherosclerosis is considered to be a chronic inflammatory disorder. Several
      autoimmune rheumatic diseases are characterized by premature and accelerated
      atherosclerosis in which both classical and non-classical risk factors contribute
      to atherogenesis. SSc is characterized by vasculopathy, and microvascular
      involvement is common. Macrovascular involvement is considered rare, although
      increased prevalence of macrovascular disease has been reported as well. Here, we
      review the literature regarding coronary artery disease, cerebrovascular disease
      and peripheral arterial disease in SSc. An increased prevalence of distal
      peripheral artery disease in the digits has been found. The prevalence of
      coronary artery disease and cerebrovascular disease is not increased, although
      studies using intima-media thickness of the carotid artery as a marker of early
      atherosclerosis showed discrepant results. Besides traditional risk factors, as
      present in the general population, non-traditional risk factors are present in
      SSc as well, such as increased lipoprotein(a), oxidized LDL, inflammation,
      vasospasm and endothelial dysfunction. Moreover, markers of vascular damage in
      atherosclerosis, like antibodies to oxidized LDL, and increased levels of soluble
      vascular adhesion molecules, have been described in association with vascular
      damage in SSc. Nevertheless, generalized premature atherosclerosis has not been
      detected in SSc. Therefore, further research is necessary to assess the
      prevalence of clinically manifest or subclinical early atherosclerosis in SSc.

PMID- 18321945
TI  - Anakinra treatment for systemic onset juvenile idiopathic arthritis (SOJIA).

PMID- 18321946
TI  - Exploring the genetic susceptibility of chronic widespread pain: the tender
      points in genetic association studies.
AB  - Chronic widespread pain (CWP) is a prevalent disorder associated with a low pain
      threshold and increased levels of psychological distress. Evidence indicates that
      there is a genetic component to CWP syndromes and pain sensitivity. Here we have
      identified and reviewed the current literature on genetic association (GA)
      studies of CWP and pain sensitivity by searching MEDLINE and EMBASE between
      January 1990 and May 2007. Of the 18 candidate genes studied to date, no
      definitive susceptibility genes have been identified. This review highlights the
      key issues for consideration when interpreting the findings from existing studies
      and in designing future studies to ensure robust and comparable findings in this
      field. Well-designed GA studies are essential if the genetic component to CWP
      aetiology is to be fully determined.

PMID- 18321947
TI  - Disease Activity Score 28-ESR bears a similar relationship to treatment decisions
      across different rheumatologists, but misclassification is too frequent to
      replace physician judgement.
AB  - OBJECTIVES: To determine whether physician factors are associated with disease
      activity status in RA, independently of 28-joint disease activity score (DAS28)
      ESR and to re-evaluate DAS28-ESR misclassification rates for identifying active
      disease in usual practice. METHODS: A prospective observational study of
      outpatients with RA seen by 17 rheumatologists across New Zealand. Active disease
      was defined by an increase in therapy together with a reason of 'active disease';
      very low disease activity was defined by a decrease in therapy together with a
      reason of 'patient well'. The independent physician effect was assessed using
      logistic regression. Sensitivity and specificity of current DAS28-ESR thresholds
      were calculated. RESULTS: In 511 patients, 178 had active disease, 220 had low
      disease activity, 37 had very low disease activity and 76 had uncertain disease
      activity status. There was no independent effect of physician upon active disease
      status (P = 0.16) with DAS28-ESR [(OR) 3.7] explaining around 50% of the
      variability in active disease status. There was a trend towards an independent
      effect of physician upon very low disease activity status (P = 0.06) and greater
      variability in the distribution of DAS28-ESR for patients in very low disease
      activity. DAS28-ESR thresholds showed a significant risk of misclassification for
      active disease. CONCLUSIONS: DAS28-ESR discriminates satisfactorily between
      groups of patients with active and non-active disease, with no evidence of
      additional physician-specific factors to explain disease activity status.
      However, DAS28-ESR is not as good for discriminating remission from non-remission
      status. There are appreciable probabilities of misclassification error, which
      make DAS28-ESR inappropriate as a sole guide for treatment decisions.

PMID- 18321948
TI  - Incidental dual source computed tomography imaging of ductal aortic coarctation,
      left subclavian artery stenosis and bicuspid aortic valve in a patient admitted
      for atypical chest pain.
AB  - A case of incidental ductal aortic coarctation with left subclavian artery
      stenosis at the origin, severely calcified and stenotic bicuspid aortic valve,
      and normal coronary arteries demonstrated by single breath hold dual source
      computed tomography angiography in a 46-year-old man admitted for acute chest
      pain is presented.

PMID- 18321949
TI  - Differential sympathetic drive to adipose tissues after food deprivation, cold
      exposure or glucoprivation.
AB  - Surplus energy is principally stored in white adipose tissue (WAT) as
      triacylglycerol and mobilized via lipolysis through norepinephrine (NE) released
      from sympathetic nervous system terminals innervating WAT. We demonstrated that
      central melanocortin receptor agonism provokes differential sympathetic drives
      across WAT pads and interscapular brown adipose tissue (IBAT). Here we tested for
      differential WAT and IBAT sympathetic drive to known lipolytic stimuli
      {glucoprivation [2-deoxy-D-glucose (2-DG)], cold exposure (5 degrees C), food
      deprivation (16 h), or both cold exposure and food deprivation} by measuring NE
      turnover (NETO). Only inguinal WAT NETO significantly increased across all
      stimuli. Dorsal subcutaneous WAT NETO only increased with glucoprivation.
      Retroperitoneal WAT NETO increased with glucoprivation, cold and cold + food
      deprivation, but not by food deprivation. Epididymal WAT NETO was unaffected by
      glucoprivation but increased with cold, cold + food deprivation or food
      deprivation, but to a small significant degree. IBAT NETO was unaffected by
      glucoprivation or food deprivation, but increased with cold and cold + food
      deprivation. Plasma glucose decreased with food deprivation and increased with 2
      DG administration or cold exposure. Plasma glycerol was increased with food
      deprivation, cold, and their combination but not with 2-DG, whereas plasma free
      fatty acids increased with food deprivation, cold + food deprivation, and 2-DG.
      These data show differential sympathetic drive to WAT and BAT for four different
      lipolytic stimuli, exemplifying the fat pad-specific pattern of WAT sympathetic
      drive across lipid-mobilizing conditions and emphasizing the need to analyze
      multiple adipose depots for measures of NETO and likely most measures.

PMID- 18321950
TI  - Redox regulation of diaphragm proteolysis during mechanical ventilation.
AB  - Prevention of oxidative stress via antioxidants attenuates diaphragm myofiber
      atrophy associated with mechanical ventilation (MV). However, the specific redox
      sensitive mechanisms responsible for this remain unknown. We tested the
      hypothesis that regulation of skeletal muscle proteolytic activity is a critical
      site of redox action during MV. Sprague-Dawley rats were assigned to five
      experimental groups: 1) control, 2) 6 h of MV, 3) 6 h of MV with infusion of the
      antioxidant Trolox, 4) 18 h of MV, and 5) 18 h of MV with Trolox. Trolox did not
      attenuate MV-induced increases in diaphragmatic levels of ubiquitin-protein
      conjugation, polyubiquitin mRNA, and gene expression of proteasomal subunits (20S
      proteasome alpha-subunit 7, 14-kDa E2, and proteasome-activating complex PA28).
      However, Trolox reduced both chymotrypsin-like and peptidylglutamyl peptide
      hydrolyzing (PGPH)-like 20S proteasome activities in the diaphragm after 18 h of
      MV. In addition, Trolox rescued diaphragm myofilament protein concentration
      (mug/mg muscle) and the percentage of easily releasable myofilament protein
      independent of alterations in ribosomal capacity for protein synthesis. In
      summary, these data are consistent with the notion that the protective effect of
      antioxidants on the diaphragm during MV is due, at least in part, to decreasing
      myofilament protein substrate availability to the proteasome.

PMID- 18321951
TI  - Branchial expression patterns of claudin isoforms in Atlantic salmon during
      seawater acclimation and smoltification.
AB  - In euryhaline teleosts, permeability changes in gill epithelia are essential
      during acclimation to changed salinity. This study examined expression patterns
      of branchial tight junction proteins called claudins, which are important
      determinants of ion selectivity and general permeability in epithelia. We
      identified Atlantic salmon genes belonging to the claudin family by screening
      expressed sequence tag libraries available at NCBI, and classification was
      performed with the aid of maximum likelihood analysis. In gill libraries, five
      isoforms (10e, 27a, 28a, 28b, and 30) were present, and quantitative PCR analysis
      confirmed tissue-specific expression in gill when compared with kidney,
      intestine, heart, muscle, brain, and liver. Expression patterns during
      acclimation of freshwater salmon to seawater (SW) and during the smoltification
      process were examined. Acclimation to SW reduced the expression of claudin 27a
      and claudin 30 but had no overall effect on claudin 28a and claudin 28b. In
      contrast, SW induced a fourfold increase in expression of claudin 10e. In accord,
      a peak in branchial claudin 10e was observed during smoltification in May,
      coinciding with optimal SW tolerance. Smoltification induced no significant
      changes in expression of the other isoforms. This study demonstrates the
      expression of an array of salmon claudin isoforms and shows that SW acclimation
      involves inverse regulation, in the gill, of claudin 10e vs. claudin 27a and 30.
      It is possible that claudin 10e is an important component of cation selective
      channels, whereas reduction in claudin 27a and 30 may change permeability
      conditions in favor of the ion secretory mode of the SW gill.

PMID- 18321952
TI  - Effect of exercise and calorie restriction on biomarkers of aging in mice.
AB  - Unlike calorie restriction, exercise fails to extend maximum life span, but the
      mechanisms that explain this disparate effect are unknown. We used a 24-wk
      protocol of treadmill running, weight matching, and pair feeding to compare the
      effects of exercise and calorie restriction on biomarkers related to aging. This
      study consisted of young controls, an ad libitum-fed sedentary group, two groups
      that were weight matched by exercise or 9% calorie restriction, and two groups
      that were weight matched by 9% calorie restriction + exercise or 18% calorie
      restriction. After 24 wk, ad libitum-fed sedentary mice were the heaviest and
      fattest. When weight-matched groups were compared, mice that exercised were
      leaner than calorie-restricted mice. Ad libitum-fed exercise mice tended to have
      lower serum IGF-1 than fully-fed controls, but no difference in fasting insulin.
      Mice that underwent 9% calorie restriction or 9% calorie restriction + exercise,
      had lower insulin levels; the lowest concentrations of serum insulin and IGF-1
      were observed in 18% calorie-restricted mice. Exercise resulted in elevated
      levels of tissue heat shock proteins, but did not accelerate the accumulation of
      oxidative damage. Thus, failure of exercise to slow aging in previous studies is
      not likely the result of increased accrual of oxidative damage and may instead be
      due to an inability to fully mimic the hormonal and/or metabolic response to
      calorie restriction.

PMID- 18321953
TI  - Gene expression profiling in human skeletal muscle during recovery from eccentric
      exercise.
AB  - We used cDNA microarrays to screen for differentially expressed genes during
      recovery from exercise-induced muscle damage in humans. Male subjects (n = 4)
      performed 300 maximal eccentric contractions, and skeletal muscle biopsy samples
      were analyzed at 3 h and 48 h after exercise. In total, 113 genes increased 3 h
      postexercise, and 34 decreased. At 48 h postexercise, 59 genes increased and 29
      decreased. On the basis of these data, we chose 19 gene changes and conducted
      secondary analyses using real-time RT-PCR from muscle biopsy samples taken from
      11 additional subjects who performed an identical bout of exercise. Real-time RT
      PCR analyses confirmed that exercise-induced muscle damage led to a rapid (3 h)
      increase in sterol response element binding protein 2 (SREBP-2), followed by a
      delayed (48 h) increase in the SREBP-2 gene targets Acyl CoA:cholesterol
      acyltransferase (ACAT)-2 and insulin-induced gene 1 (insig-1). The expression of
      the IL-1 receptor, a known regulator of SREBP-2, was also elevated after
      exercise. Taken together, these expression changes suggest a transcriptional
      program for increasing cholesterol and lipid synthesis and/or modification.
      Additionally, damaging exercise induced the expression of protein kinase H11,
      capping protein Z alpha (capZalpha), and modulatory calcineurin-interacting
      protein 1 (MCIP1), as well as cardiac ankryin repeat protein 1 (CARP1), DNAJB2, c
      myc, and junD, each of which are likely involved in skeletal muscle growth,
      remodeling, and stress management. In summary, using DNA microarrays and RT-PCR,
      we have identified novel genes that respond to skeletal muscle damage, which,
      given the known biological functions, are likely involved in recovery from and/or
      adaptation to damaging exercise.

PMID- 18321954
TI  - Modulation of activity of gustatory neurons in the hamster parabrachial nuclei by
      electrical stimulation of the ventroposteromedial nucleus of the thalamus.
AB  - The parvicellular part of the ventroposteromedial nucleus of the thalamus (VPMpc)
      is positioned at the key site between the gustatory parabrachial nuclei (PbN) and
      the gustatory cortex for relaying and processing gustatory information via the
      thalamocortical pathway. Although neuroanatomical and electrophysiological
      studies have provided information regarding the gustatory projection from PbN to
      VPMpc, the exact relationship between PbN and VPMpc, especially the efferent
      projection involving VPMpc to PbN, is obscure. Here we investigated the
      reciprocal connection between these two gustatory relays in urethane-anesthetized
      hamsters. We recorded from 114 taste-responsive neurons in the PbN and examined
      their responsiveness to electrical stimulation of the VPMpc bilaterally.
      Stimulation of either or both of the ipsilateral or contralateral VPMpc
      antidromically activated 109 gustatory PbN neurons. Seventy-two PbN neurons were
      antidromically activated after stimulation of both sides of the VPMpc, indicating
      that taste neurons in the PbN project heavily to the bilateral VPMpc. Stimulation
      of VPMpc also orthodromically activated 110 of PbN neurons, including 106 VPMpc
      projection neurons. Seventy-eight neurons were orthodromically activated
      bilaterally. Among orthodromic activations of the PbN cells, the inhibitory
      response was the dominant response; 106 cells were inhibited, including 10
      neurons that were also excited contralaterally, indicating that taste neurons in
      the PbN are subject to strong inhibitory control from VPMpc. Moreover,
      stimulation of VPMpc altered taste responses of the neurons in the PbN,
      indicating that VPMpc modulates taste responses of PbN neurons. These results may
      provide functional insight of neural circuitry for taste processing and
      modulation involving these two nuclei.

PMID- 18321955
TI  - Cyclic GMP alters the firing rate and thermosensitivity of hypothalamic neurons.
AB  - The rostral hypothalamus, especially the preoptic-anterior hypothalamus (POAH),
      contains temperature-sensitive and -insensitive neurons that form synaptic
      networks to control thermoregulatory responses. Previous studies suggest that the
      cyclic nucleotide cGMP is an important mediator in this neuronal network, since
      hypothalamic microinjections of cGMP analogs produce hypothermia in several
      species. In the present study, immunohistochemisty showed that rostral
      hypothalamic neurons contain cGMP, guanylate cyclase (necessary for cGMP
      synthesis), and CNG A2 (an important cyclic nucleotide-gated channel).
      Extracellular electrophysiological activity was recorded from different types of
      neurons in rat hypothalamic tissue slices. Each recorded neuron was classified
      according to its thermosensitivity as well as its firing rate response to 2-100
      microM 8-bromo-cGMP (a membrane-permeable cGMP analog). cGMP has specific effects
      on different neurons in the rostral hypothalamus. In the POAH, the cGMP analog
      decreased the spontaneous firing rate in 45% of temperature-sensitive and 
      insensitive neurons, an effect that is likely due to cGMP-enhanced
      hyperpolarizing K(+) currents. This decreased POAH activity could attenuate
      thermoregulatory responses and produce hypothermia during exposures to cool or
      neutral ambient temperatures. Although 8-bromo-cGMP did not affect the
      thermosensitivity of most POAH neurons, it did increase the warm sensitivity of
      neurons in other hypothalamic regions located dorsal, lateral, and posterior to
      the POAH. This increased thermosensitivity may be due to pacemaker currents that
      are facilitated by cyclic nucleotides. If some of these non-POAH thermosensitive
      neurons promote heat loss or inhibit heat production, then their increased
      thermosensitivity could contribute to cGMP-induced decreases in body temperature.

PMID- 18321956
TI  - Potent cardiovascular actions of homologous adrenomedullins in eels.
AB  - Adrenomedullin (AM), known as a multifunctional hormone in mammals, forms a
      unique family of five paralogous peptides in teleost fish. To examine their
      cardiovascular effects using homologous AMs in eels, we isolated cDNAs encoding
      four eel AMs, and named AM1 (ortholog of mammalian AM), AM2, AM3 (paralog of AM2
      generated only in teleost lineage), and AM5 according to the known teleost AM
      sequences. Unlike pufferfish, not only AM1 but AM2/3 and AM5 were expressed
      ubiquitously in various eel tissues. Synthetic mature AM1, AM2, and AM5 exhibited
      vasodepressor effects after intra-arterial injections, and the effects were more
      potent at dorsal aorta than at ventral aorta. This indicates that AMs
      preferentially act on peripheral resistance vessels rather than on branchial
      arterioles. The potency was in the order of AM2 = AM5 >> AM1 in both freshwater
      (FW) and seawater (SW) eels, which is different from the result of mammals in
      which AM1 is as potent as, or more potent than, AM2 when injected peripherally.
      The minimum effective dose of AM2 and AM5 in eels was 1/10 that of AM1 in
      mammals. The hypotension reached 50% at 1.0 nmol/kg of AM2 and AM5, which is much
      greater than atrial natriuretic peptide (20%), another potent vasodepressor
      hormone. Even with such hypotension, AMs did not change heart rate in eels. In
      addition, AM1 increased blood pressure at ventral aorta and dorsal aorta
      immediately after an initial hypotension at 5.0 nmol/kg, but not with AM2 and
      AM5. These data strongly suggest that specific receptors for AM2 and AM5 exist in
      eels, which differ from the AM1 receptors identified in mammals.

PMID- 18321957
TI  - Treatment of human brucellosis: systematic review and meta-analysis of randomised
      controlled trials.
AB  - OBJECTIVES: To determine and quantify differences in efficacy between treatment
      regimens for brucellosis. DESIGN: Systematic review and meta-analysis of
      randomised controlled trials assessing different antibiotic regimens and
      durations of treatment for human brucellosis. DATA SOURCES: PubMed, CENTRAL,
      Lilacs, conference proceedings, and bibliographies with no restrictions on
      language, study year, or publication status. Review methods Search, application
      of inclusion and exclusion criteria, data extraction, and assessment of
      methodological quality independently performed in duplicate. Primary outcomes
      were relapse and overall failure resulting from primary failure or relapse.
      Relative risks with 95% confidence intervals were calculated and pooled with a
      fixed effect model. RESULTS: 30 trials and 77 treatment arms were included.
      Overall failure was significantly higher with doxycycline-rifampicin compared to
      doxycycline-streptomycin, mainly due to a higher rate of relapse (relative risk
      2.80, 95% confidence interval 1.81 to 4.36; 13 trials, without heterogeneity).
      Results were consistent among patients with bacteraemia and complicated
      brucellosis. Doxycycline-streptomycin resulted in a significantly higher rate of
      failure than doxycycline-rifampicin-aminoglycoside (triple drug regimen) (2.50,
      1.26 to 5.00; two trials). Gentamicin was not inferior to streptomycin (1.45,
      0.52 to 4.00 for failure; two trials). Quinolones combined with rifampicin were
      significantly less effective than doxycycline combined with rifampicin or
      streptomycin (1.83, 1.11 to 3.02, for failure; five trials). Monotherapy was
      associated with a higher risk of failure than combined treatment when
      administered for a similar duration (2.56, 1.55 to 4.23; five trials). Treatment
      for six weeks or more offered an advantage over shorter treatment durations.
      CONCLUSIONS: There are significant differences in effectiveness between currently
      recommended treatment regimens for brucellosis. The preferred treatment should be
      with dual or triple regimens including an aminoglycoside.

PMID- 18321958
TI  - Treatment of brucellosis.

PMID- 18321959
TI  - African sleeping sickness.

PMID- 18321960
TI  - Safety and effectiveness of first line eflornithine for Trypanosoma brucei
      gambiense sleeping sickness in Sudan: cohort study.
AB  - OBJECTIVE: To assess the safety and effectiveness of eflornithine as first line
      treatment for human African trypanosomiasis. DESIGN: Cohort study. SETTING:
      Control programme in Ibba, southern Sudan. PARTICIPANTS: 1055 adults and children
      newly diagnosed with second stage disease in a 16 month period. MAIN OUTCOME
      MEASURES: Deaths, severe drug reactions, and cure at 24 months. RESULTS: 1055
      patients received eflornithine for 14 days (400 mg/kg/day in adults and 600
      mg/kg/day in a subgroup of 96 children). Overall, 2824 drug reactions (2.7 per
      patient) occurred during hospital stay, 1219 (43.2%) after the first week. Severe
      reactions affected 138 (13.1%) patients (mainly seizures, fever, diarrhoea, and
      bacterial infections), leading to 15 deaths. Risk factors for severe reactions
      included cerebrospinal fluid leucocyte counts > or =100x10(9)/l (adults: odds
      ratio 2.6, 95% confidence interval 1.5 to 4.6), seizures (adults: 5.9, 2.0 to
      13.3), and stupor (children: 9.3, 2.5 to 34.2). Children receiving higher doses
      did not experience increased toxicity. Follow-up data were obtained for 924
      (87.6%) patients at any follow-up but for only 533 (50.5%) at 24 months. Of 924
      cases followed, 16 (1.7%) died during treatment, 70 (7.6%) relapsed, 15 (1.6%)
      died of disease, 403 (43.6%) were confirmed cured, and 420 (45.5%) were probably
      cured. The probability of event free survival at 24 months was 0.88 (0.86 to
      0.91). Most (65.8%, 52/79) relapses and disease related deaths occurred after 12
      months. Risk factors for relapse included being male (incidence rate ratio 2.42,
      1.47 to 3.97) and cerebrospinal fluid leucocytosis: 20-99x10(9)/l (2.35, 1.36 to
      4.06); > or =100x10(9)/l (1.87, 1.07 to 3.27). Higher doses did not yield better
      effectiveness among children (0.87 v 0.85, P=0.981). Conclusions Eflornithine
      shows acceptable safety and effectiveness as first line treatment for human
      African trypanosomiasis. Relapses did occur more than 12 months after treatment.
      Higher doses in children were well tolerated but showed no advantage in
      effectiveness.

PMID- 18321961
TI  - Sortase as a target of anti-infective therapy.
AB  - The rise in antibiotic-resistant bacteria is a major concern, in particular
      because it includes many different species of pathogenic microbes. These
      "superbugs" are further characterized by high levels of virulence and disease
      associated mortality. There seems to be few new antibiotics in the drug discovery
      pipeline; recent work has sought to define and validate new drug targets. The
      assembly of surface proteins and pili in the cell wall envelope of Gram-positive
      bacteria is catalyzed by sortase. Sortase cleaves a conserved C-terminal sequence
      of these polypeptides to generate an acyl-enzyme intermediate. The acyl-enzyme is
      next resolved by nucleophilic attack by the amino groups within cell wall cross
      bridges or pilin proteins, thereby covalently attaching the polypeptides to the
      cell wall or the next pilin subunit. Sortase substrates function as adhesins,
      internalins, blood clotting and immune evasion factors, and transporters for
      nutrients across the microbial cell wall envelope; without them, most pathogens
      cannot sustain an infection. Here we review what is known about sortase catalysis
      and surface protein function, how surface protein anchoring can be inhibited, and
      what prospects such inhibition may have for anti-infective therapy.

PMID- 18321963
TI  - Human cytomegalovirus UL97 kinase activity is required for the
      hyperphosphorylation of retinoblastoma protein and inhibits the formation of
      nuclear aggresomes.
AB  - Cells infected with human cytomegalovirus in the absence of UL97 kinase activity
      produce large nuclear aggregates that sequester considerable quantities of viral
      proteins. A transient expression assay suggested that pp71 and IE1 were also
      involved in this process, and this suggestion was significant, since both
      proteins have been reported to interact with components of promyelocytic leukemia
      (PML) bodies (ND10) and also interact functionally with retinoblastoma pocket
      proteins (RB). PML bodies have been linked to the formation of nuclear
      aggresomes, and colocalization studies suggested that viral proteins were
      recruited to these structures and that UL97 kinase activity inhibited their
      formation. Proteins associated with PML bodies were examined by Western blot
      analysis, and pUL97 appeared to specifically affect the phosphorylation of RB in
      a kinase-dependent manner. Three consensus RB binding motifs were identified in
      the UL97 kinase, and recombinant viruses were constructed in which each was
      mutated to assess a potential role in the phosphorylation of RB and the
      inhibition of nuclear aggresome formation. The mutation of either the conserved
      LxCxE RB binding motif or the lysine required for kinase activity impaired the
      ability of the virus to stabilize and phosphorylate RB. We concluded from these
      studies that both UL97 kinase activity and the LxCxE RB binding motif are
      required for the phosphorylation and stabilization of RB in infected cells and
      that this effect can be antagonized by the antiviral drug maribavir. These data
      also suggest a potential link between RB function and the formation of
      aggresomes.

PMID- 18321964
TI  - Expression of gamma interferon-dependent genes is blocked independently by virion
      host shutoff RNase and by US3 protein kinase.
AB  - Gamma interferon receptor alpha (IFN-gammaR alpha) is stable but
      posttranslationally modified in herpes simplex virus 1(F) [HSV-1(F)]-infected
      cells. Studies with antibody directed to the phosphorylation site indicate that
      IFN-gammaR alpha is phosphorylated by the U(S)3 kinase. The modification is
      abolished in cells infected with DeltaU(S)3, DeltaU(L)13, or Delta(U(S)3/U(L)13)
      mutant virus. Transcripts of the IFN-gamma-dependent genes do not accumulate in
      cells transduced with the U(S)3 protein kinase and treated with IFN-gamma. In
      contrast, the accumulation of IFN-gamma-dependent gene transcripts is suppressed
      in cells infected with the wild-type virus, in cells infected with the DeltaU(S)3
      mutant virus, and to a lesser extent in the DeltaU(L)41 virus-infected cells. The
      accumulation of IFN-gamma-dependent gene transcripts in DeltaU(L)41-infected
      cells could be due at least in part to a significant delay and reduction in the
      accumulation of the U(S)3 protein. The results suggest that the expression of IFN
      gamma-dependent genes is blocked independently by the degradation of IFN-gamma
      dependent gene transcripts--a function of the virion host shutoff RNase--and by
      posttranslational modification of the IFN-gammaR alpha protein.

PMID- 18321962
TI  - Vertebrate membrane proteins: structure, function, and insights from biophysical
      approaches.
AB  - Membrane proteins are key targets for pharmacological intervention because they
      are vital for cellular function. Here, we analyze recent progress made in the
      understanding of the structure and function of membrane proteins with a focus on
      rhodopsin and development of atomic force microscopy techniques to study
      biological membranes. Membrane proteins are compartmentalized to carry out extra-
      and intracellular processes. Biological membranes are densely populated with
      membrane proteins that occupy approximately 50% of their volume. In most cases
      membranes contain lipid rafts, protein patches, or paracrystalline formations
      that lack the higher-order symmetry that would allow them to be characterized by
      diffraction methods. Despite many technical difficulties, several crystal
      structures of membrane proteins that illustrate their internal structural
      organization have been determined. Moreover, high-resolution atomic force
      microscopy, near-field scanning optical microscopy, and other lower resolution
      techniques have been used to investigate these structures. Single-molecule force
      spectroscopy tracks interactions that stabilize membrane proteins and those that
      switch their functional state; this spectroscopy can be applied to locate a
      ligand-binding site. Recent development of this technique also reveals the energy
      landscape of a membrane protein, defining its folding, reaction pathways, and
      kinetics. Future development and application of novel approaches during the
      coming years should provide even greater insights to the understanding of
      biological membrane organization and function.

PMID- 18321965
TI  - Murine cytomegalovirus m38.5 protein inhibits Bax-mediated cell death.
AB  - Many viruses encode proteins that inhibit the induction of programmed cell death
      at the mitochondrial checkpoint. Murine cytomegalovirus (MCMV) encodes the m38.5
      protein, which localizes to mitochondria and protects human HeLa cells and
      fibroblasts from apoptosis triggered by proteasome inhibitors but not from Fas
      induced apoptosis. However, the ability of this protein to suppress the apoptosis
      of murine cells and its role during MCMV infection have not been investigated
      previously. Here we show that m38.5 is expressed at early time points during MCMV
      infection. Cells infected with MCMVs lacking m38.5 showed increased sensitivity
      to cell death induced by staurosporine, MG132, or the viral infection itself
      compared to the sensitivity of cells infected with wild-type MCMV. This defect
      was eliminated when an m38.5 or Bcl-X(L) gene was inserted into the genome of a
      deletion mutant. Using fibroblasts deficient in the proapoptotic Bcl-2 family
      proteins Bak and/or Bax, we further demonstrated that m38.5 protected from Bax-
      but not Bak-mediated apoptosis and interacted with Bax in infected cells. These
      results consolidate the role of m38.5 as a viral mitochondrion-localized
      inhibitor of apoptosis and its functional similarity to the human cytomegalovirus
      UL37x1 gene product. Although the m38.5 gene is not homologous to the UL37x1 gene
      at the sequence level, m38.5 is conserved among rodent cytomegaloviruses.
      Moreover, the fact that MCMV-infected cells are protected from both Bak- and Bax
      mediated cell death suggests that MCMV possesses an additional, as-yet
      unidentified mechanism to block Bak-mediated apoptosis.

PMID- 18321966
TI  - A novel methyltransferase methylates Cucumber mosaic virus 1a protein and
      promotes systemic spread.
AB  - In mammalian and yeast systems, methyltransferases have been implicated in the
      regulation of diverse processes, such as protein-protein interactions, protein
      localization, signal transduction, RNA processing, and transcription. The
      Cucumber mosaic virus (CMV) 1a protein is essential not only for virus
      replication but also for movement. Using a yeast two-hybrid system with tobacco
      plants, we have identified a novel gene encoding a methyltransferase that
      interacts with the CMV 1a protein and have designated this gene Tcoi1 (tobacco
      CMV 1a-interacting protein 1). Tcoi1 specifically interacted with the
      methyltransferase domain of CMV 1a, and the expression of Tcoi1 was increased by
      CMV inoculation. Biochemical studies revealed that the interaction of Tcoi1 with
      CMV 1a protein was direct and that Tcoi1 methylated CMV 1a protein both in vitro
      and in vivo. The CMV 1a binding activity of Tcoi1 is in the C-terminal domain,
      which shows the methyltransferase activity. The overexpression of Tcoi1 enhanced
      the CMV infection, while the reduced expression of Tcoi1 decreased virus
      infectivity. These results suggest that Tcoi1 controls the propagation of CMV
      through an interaction with the CMV 1a protein.

PMID- 18321967
TI  - Natural selection for nucleotide usage at synonymous and nonsynonymous sites in
      influenza A virus genes.
AB  - Influenza A virus is one of the best-studied viruses and a model organism for the
      study of molecular evolution; in particular, much research has focused on
      detecting natural selection on influenza virus proteins. Here, we study the
      dynamics of the synonymous and nonsynonymous nucleotide composition of influenza
      A virus genes. In several genes, the nucleotide frequencies at synonymous
      positions drift away from the equilibria predicted from the synonymous
      substitution matrices. We investigate possible reasons for this unexpected
      behavior by fitting several regression models. Relaxation toward a mutation
      selection equilibrium following a host jump fails to explain the dynamics of the
      synonymous nucleotide composition, even if we allow for slow temporal changes in
      the substitution matrix. Instead, we find that deep internal branches of the
      phylogeny show distinct patterns of nucleotide substitution and that these
      branches strongly influence the dynamics of nucleotide composition, suggesting
      that the observed trends are at least in part a result of natural selection
      acting on synonymous sites. Moreover, we find that the dynamics of the nucleotide
      composition at synonymous and nonsynonymous sites are highly correlated,
      providing evidence that even nonsynonymous sites can be influenced by selection
      pressure for nucleotide composition.

PMID- 18321968
TI  - NEDD4L overexpression rescues the release and infectivity of human
      immunodeficiency virus type 1 constructs lacking PTAP and YPXL late domains.
AB  - The cellular ESCRT pathway functions in membrane remodeling events that accompany
      endosomal protein sorting, cytokinesis, and enveloped RNA virus budding. In the
      last case, short sequence motifs (termed late domains) within human
      immunodeficiency virus type 1 (HIV-1) p6(Gag) bind and recruit two ESCRT pathway
      proteins, TSG101 and ALIX, to facilitate virus budding. We now report that
      overexpression of the HECT ubiquitin E3 ligase, NEDD4L/NEDD4-2, stimulated the
      release of HIV-1 constructs that lacked TSG101- and ALIX-binding late domains,
      increasing infectious titers >20-fold. Furthermore, depletion of endogenous
      NEDD4L inhibited the release of these crippled viruses and led to cytokinesis
      defects. Stimulation of virus budding was dependent upon the ubiquitin ligase
      activity of NEDD4L and required only the minimal HIV-1 Gag assembly regions,
      demonstrating that Gag has ubiquitin-dependent, cis-acting late domain activities
      located outside of the p6 region. NEDD4L stimulation also required TSG101 and
      resulted in ubiquitylation of several ESCRT-I subunits, including TSG101.
      Finally, we found that TSG101/ESCRT-I was required for efficient release of Mason
      Pfizer monkey virus, which buds primarily by using a PPXY late domain to recruit
      NEDD4-like proteins. These observations suggest that NEDD4L and possibly other
      NEDD4-like proteins can ubiquitylate and activate ESCRT-I to function in virus
      budding.

PMID- 18321969
TI  - Efficient and specific rescue of human immunodeficiency virus type 1 budding
      defects by a Nedd4-like ubiquitin ligase.
AB  - To exit infected cells, human immunodeficiency virus type 1 (HIV-1) exploits the
      vacuolar protein-sorting pathway by engaging Tsg101 and ALIX through PTAP and
      LYPx(n)L late assembly (L) domains. In contrast, less-complex retroviruses often
      use PPxY L domains to recruit Nedd4 family ubiquitin ligases. Although HIV-1 Gag
      lacks PPxY motifs, we now show that the budding of various HIV-1 L-domain mutants
      is dramatically enhanced by ectopic Nedd4-2s, a native isoform with a truncated
      C2 domain. The effect of Nedd4-2s on HIV-1 budding required a catalytically
      active HECT domain and was specific, since other Nedd4 family proteins showed
      little activity and an unrelated retrovirus was not rescued. The residual C2
      domain of Nedd4-2s was critical for the enhancement of HIV-1 budding and for the
      association of Nedd4-2s with Gag, as reflected by its incorporation into virus
      like particles. Interestingly, the incorporation of Nedd4-2s also depended on its
      active site, indicating that the ability to form a thioester with ubiquitin was
      required. These data suggest a novel mechanism by which HIV-1 Gag can connect to
      cellular budding machinery.

PMID- 18321970
TI  - Casein kinase II motif-dependent phosphorylation of human papillomavirus E7
      protein promotes p130 degradation and S-phase induction in differentiated human
      keratinocytes.
AB  - The E7 proteins of human papillomaviruses (HPVs) promote S-phase reentry in
      differentiated keratinocytes of the squamous epithelia to support viral DNA
      amplification. In this study, we showed that nuclear p130 was present in the
      differentiated strata of several native squamous epithelia susceptible to HPV
      infection. In contrast, p130 was below the level of detection in HPV-infected
      patient specimens. In submerged and organotypic cultures of primary human
      keratinocytes, the E7 proteins of the high-risk mucosotrophic HPV-18, the benign
      cutaneous HPV-1, and, to a lesser extent, the low-risk mucosotropic HPV-11
      destabilized p130. This E7 activity depends on an intact pocket protein binding
      domain and a casein kinase II (CKII) phosphorylation motif. Coimmunoprecipitation
      experiments showed that both E7 domains were important for binding to p130 in
      extracts of organotypic cultures. Metabolic labeling in vivo demonstrated that E7
      proteins were indeed phosphorylated in a CKII motif-dependent manner. Moreover,
      the efficiencies of the E7 proteins of various HPV types or mutations to induce S
      phase reentry in spinous cells correlated with their relative abilities to bind
      and to destabilize p130. Collectively, these data support the notion that p130
      controls the homeostasis of the differentiated keratinocytes and is therefore
      targeted by E7 for degradation to establish conditions permissive for viral DNA
      amplification.

PMID- 18321971
TI  - Influenza A virus neuraminidase limits viral superinfection.
AB  - Enveloped viruses use multiple mechanisms to inhibit infection of a target cell
      by more than one virion. These mechanisms may be of particular importance for the
      evolution of segmented viruses, because superinfection exclusion may limit the
      frequency of reassortment of viral genes. Here, we show that cellular expression
      of influenza A virus neuraminidase (NA), but not hemagglutinin (HA) or the M2
      proton pump, inhibits entry of HA-pseudotyped retroviruses. Cells infected with
      H1N1 or H3N2 influenza A virus were similarly refractory to HA-mediated infection
      and to superinfection with a second influenza A virus. Both HA-mediated entry and
      viral superinfection were rescued by the neuraminidase inhibitors oseltamivir
      carboxylate and zanamivir. These inhibitors also prevented the removal of alpha
      2,3- and alpha-2,6-linked sialic acid observed in cells expressing NA or infected
      with influenza A viruses. Our data indicate that NA alone among viral proteins
      limits influenza A virus superinfection.

PMID- 18321972
TI  - Nucleolin is required for an efficient herpes simplex virus type 1 infection.
AB  - Productive infection by herpes simplex virus type 1 (HSV-1), which occurs in the
      host cell nucleus, is accompanied by dramatic modifications of the nuclear
      architecture, including profound alterations of nucleolar morphology. Here, we
      show that the three most abundant nucleolar proteins--nucleolin, B23, and
      fibrillarin--are redistributed out of the nucleoli as a consequence of HSV-1
      infection. We show that the amount of nucleolin increases progressively during
      the course of infection. We demonstrate for the first time that a nucleolar
      protein, i.e., nucleolin, colocalizes with ICP8 in the viral replication
      compartments, at the time when viral replication is effective, suggesting an
      involvement of nucleolin in the HSV-1 DNA replication process. At later times of
      infection, a granular form of nucleolin localizes to the cytoplasm, in structures
      that display the characteristic features of aggresomes, indicating that this form
      of nucleolin is very probably destined for degradation. The delocalization of
      nucleolin from the nucleoli requires the viral ICP4 protein or a factor(s) whose
      expression involves ICP4. Using small interfering RNA technology, we show that
      viral replication requires a high level of nucleolin expression, demonstrating
      for the first time a direct role for a nucleolar protein in herpes simplex virus
      biology.

PMID- 18321973
TI  - Virion-wide protein interactions of Kaposi's sarcoma-associated herpesvirus.
AB  - Herpesvirus virions are highly organized structures built through specific
      protein-protein interactions. Thus, revelation of the protein interactions among
      virion proteins will shed light on the processes and the mechanisms of virion
      formation. Recently, we identified 24 virion proteins of Kaposi's sarcoma
      associated herpesvirus (KSHV), using a proteomic approach (F. X. Zhu et al., J.
      Virol. 79:800-811, 2005). In the current study, a comprehensive analysis of
      protein-protein interaction between KSHV virion proteins was carried out using
      yeast two-hybrid (Y2H) and coimmunoprecipitation (co-IP) approaches. Every
      pairwise combination between KSHV tegument and capsid proteins, between tegument
      and envelope proteins, and among tegument proteins was tested for possible binary
      interaction. Thirty-seven protein-protein interactions were identified by both
      Y2H and co-IP analyses. The results revealed interactions between tegument and
      capsid proteins such as that of open reading frame 64 (ORF64) with ORF25 (major
      capsid protein [MCP]), ORF62 (triplex-1 [TRI-1]), and ORF26 (TRI-2). Many
      interactions were detected among the tegument proteins. ORF64 was found to
      interact with several tegument proteins including ORF11, ORF21, ORF33, ORF45,
      ORF63, ORF75, and ORF64 itself, suggesting that ORF64 may serve as a hub protein
      and play a role in recruiting tegument proteins during tegumentation and virion
      assembly. Our investigation also revealed redundant interactions between tegument
      proteins and envelope glycoproteins. These interactions are believed to
      contribute to final envelopment in virion assembly. Overall, this study allows us
      to establish a virion-wide protein interaction map, which provides insight into
      the architecture of the KSHV virion and sets up a foundation for exploring the
      functions of these proteins in viral particle assembly.

PMID- 18321974
TI  - CD63 is not required for production of infectious human immunodeficiency virus
      type 1 in human macrophages.
AB  - During the assembly of human immunodeficiency virus type 1 (HIV-1) particles, the
      tetraspanin CD63 can be incorporated into the viral membrane. Indeed, cell
      surface tetraspanin microdomains that include CD63 have been proposed as sites
      for virus release. In addition, antibodies against CD63 can inhibit HIV infection
      of macrophages. In this cell type, HIV assembles into intracellularly sequestered
      plasma membrane domains that contain several other tetraspanins, including CD81,
      CD9, and CD53. CD63 is recruited to this domain following HIV infection.
      Together, these observations suggest that CD63 may have some function in the
      assembly of infectious virus particles and/or the infectivity of assembled
      virions. Here we have used RNA interference to knock down CD63 expression in
      monocyte-derived primary macrophages. We show that in the absence of CD63, HIV
      assembly is quantitatively comparable to that seen in CD63-expressing macrophages
      and that virus assembly occurs on compartments positive for CD81, CD9, and CD53.
      Moreover, the infectivity of macrophage-derived virus is unaffected by the loss
      of CD63. Together, our results indicate that at least in tissue culture, CD63
      expression is not required for either the production or the infectivity of HIV-1.

PMID- 18321975
TI  - Uniocular anterior chamber inoculation of a tumor necrosis factor alpha
      expressing recombinant of herpes simplex virus type 1 results in more rapid
      destruction and increased viral replication in the retina of the uninoculated
      eye.
AB  - Tumor necrosis factor alpha (TNF-alpha) has been shown to have a protective role
      in the eyes and brains of herpes simplex virus type 1 (HSV-1)-infected mice. To
      determine whether overexpression of TNF-alpha affected the course of virus
      infection following uniocular anterior chamber inoculation, a recombinant of HSV
      1 that produces TNF-alpha constitutively (KOSTNF) was constructed. BALB/c mice
      were injected with the TNF-alpha recombinant, a recombinant containing the pCI
      plasmid, a recombinant rescue virus, or the parental virus. Flow cytometry and
      immunohistochemistry were used to identify virus-infected cells and to determine
      the numbers and types of infiltrating inflammatory cells in the uninjected eyes.
      Virus titers were determined by plaque assay. There were no differences among the
      groups in virus titers or the route and timing of virus spread in the injected
      eyes or in the suprachiasmatic nuclei. However, in the uninjected eyes of KOSTNF
      infected mice, TNF-alpha expression was increased and there were more viral
      antigen-positive cells and immune inflammatory cells. There was earlier
      microscopic evidence of retinal infection and destruction in these mice, and the
      titers of virus in the uninjected eyes were significantly increased in KOSTNF
      infected mice on day 7 postinfection compared with those of KOSpCI-, KOS6beta
      rescue-, or KOS6beta-infected mice. The results suggest that instead of
      moderating infection and reducing virus spread, overexpression of TNF-alpha has
      deleterious effects due to increased inflammation and virus infection that result
      in earlier destruction of the retina of the uninoculated eye.

PMID- 18321976
TI  - Genomic analysis of closely related astroviruses.
AB  - To understand astrovirus biology, it is essential to understand factors
      associated with its evolution. The current study reports the genomic sequences of
      nine novel turkey astrovirus (TAstV) type 2-like clinical isolates. This
      represents, to our knowledge, the largest genomic-length data set available for
      any one astrovirus type. The comparison of these TAstV sequences suggests that
      the TAstV species contains multiple subtypes and that recombination events have
      occurred across the astrovirus genome. In addition, the analysis of the capsid
      gene demonstrated evidence for both site-specific positive selection and
      purifying selection.

PMID- 18321977
TI  - Mitochondrial dysfunction in lyssavirus-induced apoptosis.
AB  - Lyssaviruses are highly neurotropic viruses associated with neuronal apoptosis.
      Previous observations have indicated that the matrix proteins (M) of some
      lyssaviruses induce strong neuronal apoptosis. However, the molecular
      mechanism(s) involved in this phenomenon is still unknown. We show that for
      Mokola virus (MOK), a lyssavirus of low pathogenicity, the M (M-MOK) targets
      mitochondria, disrupts the mitochondrial morphology, and induces apoptosis. Our
      analysis of truncated M-MOK mutants suggests that the information required for
      efficient mitochondrial targeting and dysfunction, as well as caspase-9
      activation and apoptosis, is held between residues 46 and 110 of M-MOK. We used a
      yeast two-hybrid approach, a coimmunoprecipitation assay, and confocal microscopy
      to demonstrate that M-MOK physically associates with the subunit I of the
      cytochrome c (cyt-c) oxidase (CcO) of the mitochondrial respiratory chain; this
      is in contrast to the M of the highly pathogenic Thailand lyssavirus (M-THA). M
      MOK expression induces a significant decrease in CcO activity, which is not the
      case with M-THA. M-MOK mutations (K77R and N81E) resulting in a similar sequence
      to M-THA at positions 77 and 81 annul cyt-c release and apoptosis and restore CcO
      activity. As expected, the reverse mutations, R77K and E81N, introduced in M-THA
      induce a phenotype similar to that due to M-MOK. These features indicate a novel
      mechanism for energy depletion during lyssavirus-induced apoptosis.

PMID- 18321978
TI  - Importance of protease cleavage sites within and flanking human immunodeficiency
      virus type 1 transframe protein p6* for spatiotemporal regulation of protease
      activation.
AB  - The human immunodeficiency virus type 1 (HIV-1) protease (PR) has recently been
      shown to be inhibited by its propeptide p6* in vitro. As p6* itself is a PR
      substrate, the primary goal of this study was to determine the importance of p6*
      cleavage for HIV-1 maturation and infectivity. For that purpose, short peptide
      variants mimicking proposed cleavage sites within and flanking p6* were designed
      and analyzed for qualitative and quantitative hydrolysis in vitro. Proviral
      clones comprising the selected cleavage site mutations were established and
      analyzed for Gag and Pol processing, virus maturation, and infectivity in
      cultured cells. Amino-terminal cleavage site mutation caused aberrant processing
      of nucleocapsid proteins and delayed replication kinetics. Blocking the internal
      cleavage site resulted in the utilization of a flanking site at a significantly
      decreased hydrolysis rate in vitro, which however did not affect Gag-Pol
      processing and viral replication. Although mutations blocking cleavage at the p6*
      carboxyl terminus yielded noninfectious virions exhibiting severe Gag processing
      defects, mutations retarding hydrolysis of this cleavage site neither seemed to
      impact viral infectivity and propagation in cultured cells nor seemed to
      interfere with overall maturation of released viruses. Interestingly, these
      mutants were shown to be clearly disadvantaged when challenged with wild-type
      virus in a dual competition assay. In sum, we conclude that p6* cleavage is
      absolutely essential to allow complete activation of the PR and subsequent
      processing of the viral precursors.

PMID- 18321979
TI  - Mutations in the human immunodeficiency virus type 1 polypurine tract (PPT)
      reduce the rate of PPT cleavage and plus-strand DNA synthesis.
AB  - Previously, we analyzed the effects of point mutations in the human
      immunodeficiency virus type 1 (HIV-1) polypurine tract (PPT) and found that some
      mutations affected both titer and cleavage specificity. We used HIV-1 vectors
      containing two PPTs and the D116N integrase active-site mutation in a cell-based
      assay to measure differences in the relative rates of PPT processing and
      utilization. The relative rates were measured by determining which of the two
      PPTs in the vector is used to synthesize viral DNA. The results indicate that
      mutations that have subtle effects on titer and cleavage specificity can have
      dramatic effects on rates of PPT generation and utilization.

PMID- 18321980
TI  - Distinct ex vivo susceptibility of B-cell subsets to epstein-barr virus infection
      according to differentiation status and tissue origin.
AB  - Epstein-Barr virus (EBV) uses tonsils as the portal of entry to establish
      persistent infection. EBV is found in various B-cell subsets in tonsils but
      exclusively in memory B cells in peripheral blood. The in vitro susceptibilities
      of B-cell subsets to EBV infection have been studied solely qualitatively. In
      this work, we examined quantitatively the in vitro susceptibilities of various B
      cell subsets from different tissue origins to EBV infection. First, we
      established a centrifugation-based inoculation protocol (spinoculation) that
      resulted in a significantly increased proportion of infected cells compared to
      that obtained by conventional inoculation, enabling a detailed susceptibility
      analysis. Importantly, B-cell infection occurred via the known EBV receptors and
      infected cells showed EBV mRNA expression patterns similar to those observed
      after conventional inoculation, validating our approach. Tonsillar naive and
      memory B cells were infected ex vivo at similar frequencies. In contrast, memory
      B cells from blood, which represent B cells from various lymphoid tissues, were
      infected at lower frequencies than their naive counterparts. Immunoglobulin A
      (IgA)-positive or IgG-positive tonsillar memory B cells were significantly more
      susceptible to EBV infection than IgM-positive counterparts. Memory B cells were
      transformed with lower efficiency than naive B cells. This result was paralleled
      by lower proliferation rates. In summary, these data suggest that EBV exploits
      the B-cell differentiation status and tissue origin to establish persistent
      infection.

PMID- 18321981
TI  - Sdmg1 is a conserved transmembrane protein associated with germ cell sex
      determination and germline-soma interactions in mice.
AB  - In mammals, the supporting cell lineage in an embryonic gonad communicates the
      sex-determining decision to various sexually dimorphic cell types in the
      developing embryo, including the germ cells. However, the molecular nature of the
      sex-determining signals that pass from the supporting cells to the germ cells is
      not well understood. We have identified a conserved transmembrane protein, Sdmg1,
      owing to its male-specific expression in mouse embryonic gonads. Sdmg1 is
      expressed in the Sertoli cells of embryonic testes from 12.5 dpc, and in
      granulosa cells of growing follicles in adult ovaries. In Sertoli cells, Sdmg1 is
      localised to endosomes, and knock-down of Sdmg1 in Sertoli cell lines causes mis
      localisation of the secretory SNARE Stx2 and defects in membrane trafficking.
      Upregulation of Sdmg1 appears to be part of a larger programme of changes to
      membrane trafficking pathways in embryonic Sertoli cells, and perturbing
      secretion in male embryonic gonads in organ culture causes male-to-female germ
      cell sex reversal. These data suggest that changes that occur in the cell biology
      of embryonic Sertoli cells may facilitate the communication of male sex
      determining decisions to the germ cells during embryonic development.

PMID- 18321982
TI  - Six2 functions redundantly immediately downstream of Hoxa2.
AB  - Hox transcription factors control morphogenesis along the head-tail axis of
      bilaterians. Because their direct functional targets are still poorly understood
      in vertebrates, it remains unclear how the positional information encoded by Hox
      genes is translated into morphogenetic changes. Here, we conclusively demonstrate
      that Six2 is a direct downstream target of Hoxa2 in vivo and show that the
      ectopic expression of Six2, observed in the absence of Hoxa2, contributes to the
      Hoxa2 mouse mutant phenotype. We propose that Six2 acts to mediate Hoxa2 control
      over the insulin-like growth factor pathway during branchial arch development.

PMID- 18321983
TI  - APC/CFzr/Cdh1 promotes cell cycle progression during the Drosophila endocycle.
AB  - The endocycle is a commonly observed variant cell cycle in which cells undergo
      repeated rounds of DNA replication with no intervening mitosis. How the cell
      cycle machinery is modified to transform a mitotic cycle into endocycle has long
      been a matter of interest. In both plants and animals, the transition from the
      mitotic cycle to the endocycle requires Fzr/Cdh1, a positive regulator of the
      Anaphase-Promoting Complex/Cyclosome (APC/C). However, because many of its
      targets are transcriptionally downregulated upon entry into the endocycle, it
      remains unclear whether the APC/C functions beyond the mitotic/endocycle
      boundary. Here, we report that APC/C Fzr/Cdh1 activity is required to promote the
      G/S oscillation of the Drosophila endocycle. We demonstrate that compromising
      APC/C activity, after cells have entered the endocycle, inhibits DNA replication
      and results in the accumulation of multiple APC/C targets, including the mitotic
      cyclins and Geminin. Notably, our data suggest that the activity of APC/C
      Fzr/Cdh1 during the endocycle is not continuous but is cyclic, as demonstrated by
      the APC/C-dependent oscillation of the pre-replication complex component Orc1.
      Taken together, our data suggest a model in which the cyclic activity of APC/C
      Fzr/Cdh1 during the Drosophila endocycle is driven by the periodic inhibition of
      Fzr/Cdh1 by Cyclin E/Cdk2. We propose that, as is observed in mitotic cycles,
      during endocycles, APC/C Fzr/Cdh1 functions to reduce the levels of the mitotic
      cyclins and Geminin in order to facilitate the relicensing of DNA replication
      origins and cell cycle progression.

PMID- 18321984
TI  - Drosophila fragile X mental retardation protein developmentally regulates
      activity-dependent axon pruning.
AB  - Fragile X Syndrome (FraX) is a broad-spectrum neurological disorder with symptoms
      ranging from hyperexcitability to mental retardation and autism. Loss of the
      fragile X mental retardation 1 (fmr1) gene product, the mRNA-binding
      translational regulator FMRP, causes structural over-elaboration of dendritic and
      axonal processes, as well as functional alterations in synaptic plasticity at
      maturity. It is unclear, however, whether FraX is primarily a disease of
      development, a disease of plasticity or both: a distinction that is vital for
      engineering intervention strategies. To address this crucial issue, we have used
      the Drosophila FraX model to investigate the developmental function of Drosophila
      FMRP (dFMRP). dFMRP expression and regulation of chickadee/profilin coincides
      with a transient window of late brain development. During this time, dFMRP is
      positively regulated by sensory input activity, and is required to limit axon
      growth and for efficient activity-dependent pruning of axon branches in the
      Mushroom Body learning/memory center. These results demonstrate that dFMRP has a
      primary role in activity-dependent neural circuit refinement during late brain
      development.

PMID- 18321985
TI  - Incidental acute infarcts identified on diffusion-weighted images: a university
      hospital-based study.
AB  - BACKGROUND AND PURPOSE: Pathogenesis of leukoaraiosis is incompletely understood
      and accumulation of small infarctions may be one of the possible sources of such
      white matter lesions. Thus, the purpose of this study was to identify the rate of
      incident infarction as depicted on diffusion-weighted images (DWIs) obtained from
      a general patient population. MATERIALS AND METHODS: During the 4-year study
      period, a total of 60 patients (36 men and 24 women) had an incidental DWI
      defined infarction without overt clinical symptoms suggestive of a stroke or a
      transient ischemic attack. All of the MR images were obtained by using a similar
      protocol on 2 identical 1.5T whole-body scanners. The patient's vascular risk
      factors, as well as the presence of white matter lesions (WMLs) on MR imaging and
      atheromatous changes on MR angiography, were assessed retrospectively. The
      incidental DWI-defined infarcts were also characterized in terms of their
      lateralization, lobe, and specific location. RESULTS: A total of 16,206
      consecutive brain MR images were done during the study period; the overall
      incidence of incidental infarcts was 0.37%. Most of these patients with an
      incidental infarct had vascular risk factors and WMLs on MR images. Most of these
      patients (80%) had a single lesion on DWI. A total of 88 lesions were identified;
      most were located in the white matter of the supratentorial brain, primarily in
      the frontoparietal lobes. There were also lesions involving the brain stem (n =
      2). The lesions involving cerebrum were more commonly located in the right side
      (right to left = 52:34). CONCLUSION: Small, DWI-defined acute brain infarctions
      can be found incidentally in an asymptomatic population; this finding may
      account, at least in part, for the pathogenesis of WMLs identified on MR imaging.

PMID- 18321986
TI  - Imaging of intralabyrinthine schwannomas: a retrospective study of 52 cases with
      emphasis on lesion growth.
AB  - BACKGROUND AND PURPOSE: Only a few case reports and small series of
      intralabyrinthine schwannomas (ILSs) have been reported. The purpose of this
      study was to assess prevalence, MR characteristics, location, clinical
      management, and growth potential/patterns of ILSs in the largest series reported.
      MATERIALS AND METHODS: Lesion localization, MR characteristics, lesion growth,
      and clinical management were reviewed in 52 patients diagnosed with an ILS
      between February 1991 and August 2007 in 2 referral centers. The number of ILSs
      and vestibulocochlear schwannomas in the cerebellopontine angle/internal auditory
      canal was compared to assess the prevalence. RESULTS: ILSs most frequently
      originate intracochlearly, are hyperintense on unenhanced T1-weighted images,
      enhance strongly after gadolinium administration, and are sharply circumscribed
      and hypointense on thin heavily T2-weighted 3D images. The scala tympani is more
      frequently or more extensively involved than the scala vestibuli. Follow-up MR
      imaging, available in 27 patients, showed growth in 59% of subjects. Growth was
      seen from the scala tympani into the scala vestibuli and from the scala vestibuli
      to the saccule and vice versa. Twelve lesions were resected, and the diagnosis of
      ILS histopathologically confirmed. CONCLUSION: ILSs can account for up to 10% of
      all vestibulocochlear schwannomas in centers specializing in temporal bone
      imaging, grow in more than 50%, and are most frequently found intracochlearly,
      often anteriorly between the basal and second turn. Cochlear ILSs most often
      originate in the scala tympani and only later grow into the scala vestibuli.
      Growth can occur from the cochlea into the vestibule or vice versa through the
      anatomic open connection between the perilymphatic spaces in the scala vestibuli
      and around the saccule.

PMID- 18321987
TI  - Hyperecho-turbo spin-echo sequences at 3T: clinical application in
      neuroradiology.
AB  - BACKGROUND AND PURPOSE: Hyperecho-turbo spin-echo (hyperTSE) sequences were
      developed to reduce the specific absorption rate (SAR), especially at high fields
      such as 3T and above. The purpose of this study was to quantitatively and
      qualitatively assess the detection of neuroradiologic pathologies by hyperTSE in
      comparison with standard turbo spin-echo (TSE180 degrees) sequences. MATERIALS
      AND METHODS: TSE180 degrees and hyperTSE images with parameters adapted for equal
      T2 contrast were acquired on a 3T whole-body system in 51 patients with 54
      cerebral pathologies. Region-of-interest analysis was performed of signal
      intensities of pathologies, normal white and gray matter, CSF, and the SD of
      noise. Signal intensity-to-noise ratios (SNRs) and contrast-to-noise ratios
      (CNRs) for healthy tissues and pathologies were determined. A qualitative rating
      concerning artifacts, lesion conspicuity, and image quality was performed by 2
      experienced neuroradiologists. RESULTS: HyperTSE sequences were equivalent to
      standard TSE180 degrees sequences for the CNR of pathologies and of the contrast
      between gray and white matter. The SNR of gray and white matter and CSF were also
      the same. The CNRs of the pathologies in hyperTSE and TSE180 degrees images were
      strongly correlated with each other (r = 0.93, P = .001). The visual rating of
      images revealed no significant differences between hyperTSE and TSE180 degrees.
      CONCLUSION: HyperTSE sequences proved to be qualitatively and quantitatively
      equivalent to TSE180 degrees sequences in the detection of high- and low-signal
      intensity lesions. They provide equal CNR of pathologies and of gray minus white
      matter and reduce the imaging restrictions of conventional TSE180 degrees imposed
      by SAR limitations at 3T.

PMID- 18321988
TI  - The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis
      in autophagy.
AB  - Two ubiquitin-like molecules, Atg12 and LC3/Atg8, are involved in autophagosome
      biogenesis. Atg12 is conjugated to Atg5 and forms an approximately 800-kDa
      protein complex with Atg16L (referred to as Atg16L complex). LC3/Atg8 is
      conjugated to phosphatidylethanolamine and is associated with autophagosome
      formation, perhaps by enabling membrane elongation. Although the Atg16L complex
      is required for efficient LC3 lipidation, its role is unknown. Here, we show that
      overexpression of Atg12 or Atg16L inhibits autophagosome formation.
      Mechanistically, the site of LC3 lipidation is determined by the membrane
      localization of the Atg16L complex as well as the interaction of Atg12 with Atg3,
      the E2 enzyme for the LC3 lipidation process. Forced localization of Atg16L to
      the plasma membrane enabled ectopic LC3 lipidation at that site. We propose that
      the Atg16L complex is a new type of E3-like enzyme that functions as a scaffold
      for LC3 lipidation by dynamically localizing to the putative source membranes for
      autophagosome formation.

PMID- 18321989
TI  - Cleavage of Mcd1 by caspase-like protease Esp1 promotes apoptosis in budding
      yeast.
AB  - Over the last decade, yeast has been used successfully as a model system for
      studying the molecular mechanism of apoptotic cell death. Here, we report that
      Mcd1, the yeast homology of human cohesin Rad21, plays an important role in
      hydrogen peroxide-induced apoptosis in yeast. On induction of cell death, Mcd1 is
      cleaved and the C-terminal fragment is translocated from nucleus into
      mitochondria, causing the decrease of mitochondrial membrane potential and the
      amplification of cell death in a cytochrome c-dependent manner. We further
      demonstrate that the caspase-like protease Esp1 has dual functions and that it is
      responsible for the cleavage of Mcd1 during the hydrogen peroxide-induced
      apoptosis. When apoptosis is induced, Esp1 is released from the anaphase
      inhibitor Pds1. The activated Esp1 acts as caspase-like protease for the cleavage
      of Mcd1, which enhances the cell death via its translocation from nucleus to
      mitochondria.

PMID- 18321990
TI  - Aurora A regulates the activity of HURP by controlling the accessibility of its
      microtubule-binding domain.
AB  - HURP is a spindle-associated protein that mediates Ran-GTP-dependent assembly of
      the bipolar spindle and promotes chromosome congression and interkinetochore
      tension during mitosis. We report here a biochemical mechanism of HURP regulation
      by Aurora A, a key mitotic kinase that controls the assembly and function of the
      spindle. We found that HURP binds to microtubules through its N-terminal domain
      that hyperstabilizes spindle microtubules. Ectopic expression of this domain
      generates defects in spindle morphology and function that reduce the level of
      tension across sister kinetochores and activate the spindle checkpoint.
      Interestingly, the microtubule binding activity of this N-terminal domain is
      regulated by the C-terminal region of HURP: in its hypophosphorylated state, C
      terminal HURP associates with the microtubule-binding domain, abrogating its
      affinity for microtubules. However, when the C-terminal domain is phosphorylated
      by Aurora A, it no longer binds to N-terminal HURP, thereby releasing the
      inhibition on its microtubule binding and stabilizing activity. In fact, ectopic
      expression of this C-terminal domain depletes endogenous HURP from the mitotic
      spindle in HeLa cells in trans, suggesting the physiological importance for this
      mode of regulation. We concluded that phosphorylation of HURP by Aurora A
      provides a regulatory mechanism for the control of spindle assembly and function.

PMID- 18321991
TI  - The integrin-coupled signaling adaptor p130Cas suppresses Smad3 function in
      transforming growth factor-beta signaling.
AB  - Reciprocal cooperative signaling by integrins and growth factor receptors at G1
      phase during cell cycle progression is well documented. By contrast, little is
      known about the cross-talk between integrin and transforming growth factor (TGF)
      beta signaling. Here, we show that integrin signaling counteracts the inhibitory
      effects of TGF-beta on cell growth and that this effect is mediated by p130Cas
      (Crk-associated substrate, 130 kDa). Adhesion to fibronectin or laminin reduces
      TGF-beta-induced Smad3 phosphorylation and thus inhibits TGF-beta-mediated growth
      arrest; loss of p130Cas abrogates these effects. Loss and gain of function
      studies demonstrated that, once tyrosine-phosphorylated via integrin signaling,
      p130Cas binds to Smad3 and reduces phosphorylation of Smad3. That in turn leads
      to inhibition of p15 and p21 expression and facilitation of cell cycle
      progression. Thus, p130Cas-mediated control of TGF-beta/Smad signaling may
      provide an additional clue to the mechanism underlying resistance to TGF-beta
      induced growth inhibition.

PMID- 18321992
TI  - The Yak1 kinase is involved in the initiation and maintenance of hyphal growth in
      Candida albicans.
AB  - Members of the dual-specificity tyrosine-phosphorylated and regulated kinase
      (DYRK) family perform a variety of functions in eukaryotes. We used gene
      disruption, targeted pharmacologic inhibition, and genome-wide transcriptional
      profiling to dissect the function of the Yak1 DYRK in the human fungal pathogen
      Candida albicans. C. albicans strains with mutant yak1 alleles showed defects in
      the yeast-to-hypha transition and in maintaining hyphal growth. They also could
      not form biofilms. Despite their in vitro filamentation defect, C. albicans
      yak1Delta/yak1Delta mutants remained virulent in animal models of systemic and
      oropharyngeal candidiasis. Transcriptional profiling showed that Yak1 was
      necessary for the up-regulation of only a subset of hypha-induced genes. Although
      downstream targets of the Tec1 and Bcr1 transcription factors were down-regulated
      in the yak1Delta/yak1Delta mutant, TEC1 and BCR1 were not. Furthermore, 63% of
      Yak1-dependent, hypha-specific genes have been reported to be negatively
      regulated by the transcriptional repressor Tup1 and inactivation of TUP1 in the
      yak1Delta/yak1Delta mutant restored filamentation, suggesting that Yak1 may
      function upstream of Tup1 in governing hyphal emergence and maintenance.

PMID- 18321993
TI  - Collagen fibril flow and tissue translocation coupled to fibroblast migration in
      3D collagen matrices.
AB  - In nested collagen matrices, human fibroblasts migrate from cell-containing
      dermal equivalents into surrounding cell-free outer matrices. Time-lapse
      microscopy showed that in addition to cell migration, collagen fibril flow
      occurred in the outer matrix toward the interface with the dermal equivalent.
      Features of this flow suggested that it depends on the same cell motile machinery
      that normally results in cell migration. Collagen fibril flow was capable of
      producing large-scale tissue translocation as shown by closure of a approximately
      1-mm gap between paired dermal equivalents in floating, nested collagen matrices.
      Our findings demonstrate that when fibroblasts interact with collagen matrices,
      tractional force exerted by the cells can couple to matrix translocation as well
      as to cell migration.

PMID- 18321994
TI  - Interplay between S-cyclin-dependent kinase and Dbf4-dependent kinase in
      controlling DNA replication through phosphorylation of yeast Mcm4 N-terminal
      domain.
AB  - Cyclin-dependent (CDK) and Dbf4-dependent (DDK) kinases trigger DNA replication
      in all eukaryotes, but how these kinases cooperate to regulate DNA synthesis is
      largely unknown. Here, we show that budding yeast Mcm4 is phosphorylated in vivo
      during S phase in a manner dependent on the presence of five CDK phosphoacceptor
      residues within the N-terminal domain of Mcm4. Mutation to alanine of these five
      sites (mcm4-5A) abolishes phosphorylation and decreases replication origin firing
      efficiency at 22 degrees C. Surprisingly, the loss of function mcm4-5A mutation
      confers cold and hydroxyurea sensitivity to DDK gain of function conditions
      (mcm5/bob1 mutation or DDK overexpression), implying that phosphorylation of Mcm4
      by CDK somehow counteracts negative effects produced by ectopic DDK activation.
      Deletion of the S phase cyclins Clb5,6 is synthetic lethal with mcm4-5A and
      mimics its effects on DDK up mutants. Furthermore, we find that Clb5 expressed
      late in the cell cycle can still suppress the lethality of clb5,6Delta bob1
      cells, whereas mitotic cyclins Clb2, 3, or 4 expressed early cannot. We propose
      that the N-terminal extension of eukaryotic Mcm4 integrates regulatory inputs
      from S-CDK and DDK, which may play an important role for the proper assembly or
      stabilization of replisome-progression complexes.

PMID- 18321995
TI  - Stimulus-dependent impairment of the neutrophil oxidative burst response in
      lactoferrin-deficient mice.
AB  - Lactoferrin (LF) is an iron-binding protein found in milk, mucosal secretions,
      and the secondary granules of neutrophils in which it is considered to be an
      important factor in the innate immune response against microbial infections.
      Moreover, LF deficiency in the secondary granules of neutrophils has long been
      speculated to contribute directly to the hypersusceptibility of specific granule
      deficiency (SGD) patients to severe, life-threatening bacterial infections.
      However, the exact physiological significance of LF in neutrophil-mediated host
      defense mechanisms remains controversial and has not yet been clearly established
      in vivo using relevant animal models. In this study, we used lactoferrin knockout
      (LFKO) mice to directly address the selective role of LF in the host defense
      response of neutrophils and to determine its contribution, if any, to the
      phenotype of SGD. Neutrophil maturation, migration, phagocytosis, granule
      release, and antimicrobial response to bacterial challenge were unaffected in
      LFKO mice. Interestingly, a stimulus-dependent defect in the oxidative burst
      response of LFKO neutrophils was observed in that normal activation was seen in
      response to opsonized bacteria whereas an impaired response was evident after
      phorbol myristate-13-acetate stimulation. Taken together, these results indicate
      that although LF deficiency alone is not a primary cause of the defects
      associated with SGD, this protein does play an immunomodulatory role in the
      oxidative burst response of neutrophils.

PMID- 18321996
TI  - Inhibition of CCN6 (Wnt-1-induced signaling protein 3) down-regulates E-cadherin
      in the breast epithelium through induction of snail and ZEB1.
AB  - The cysteine-rich protein CCN6 [or Wnt-1-induced signaling protein 3 (WISP3)]
      exerts tumor-suppressive effects in aggressive inflammatory breast cancer. Loss
      of CCN6 is associated with poorly differentiated phenotypes and increased
      invasion. Here, we show that reduction of CCN6 expression occurs in 60% of
      invasive breast carcinomas and is associated with axillary lymph node metastases.
      Furthermore, low CCN6 expression in invasive carcinoma tissue samples correlates
      with reduced expression of E-cadherin. In vitro, RNA interference knockdown of
      CCN6 in two benign human mammary epithelial cell lines (HME and MCF10A) decreased
      expression of E-cadherin protein and mRNA and reduced activity of the E-cadherin
      promoter; this reduction was dependent on intact E-box elements. CCN6 knockdown
      in HME cells resulted in up-regulation of the E-cadherin transcriptional
      repressors Snail and ZEB1 and enhanced their recruitment and binding to the E
      cadherin promoter as analyzed by chromatin immunoprecipitation assays. Small
      interfering RNA-mediated knockdown of ZEB1 or Snail blocked the down-regulation
      of E-cadherin caused by CCN6 inhibition. These data show, for the first time,
      that CCN6 expression is reduced or lost in a substantial number of invasive
      breast carcinomas and that CCN6 modulates transcriptional repressors of E
      cadherin. Together, our results lead to a new hypothesis that Snail and ZEB1 are
      downstream of CCN6 and play a critical role in CCN6-mediated regulation of E
      cadherin in breast cancer.

PMID- 18321998
TI  - The in vivo rate of somatic adenomatous polyposis coli mutation.
AB  - Cancer arises through successive somatic mutations/epimutations of oncogenes and
      tumor-suppressor genes. Accurate estimates of the rates at which these
      (epi)mutations occur are a vital but missing link in our emerging quantitative
      understanding of tumorigenesis. Their absence has hindered arguments concerning
      the importance of genetic instability in tumorigenesis and the number of
      mutations that precede malignant conversion of healthy cell lineages. Herein, a
      novel method for calculating the in vivo mutation rate of the adenomatous
      polyposis coli (APC) tumor-suppressor gene is presented. The large majority of
      bowel cancers are thought to be initiated by a partial loss of APC function, with
      the age-onset pattern dramatically altered for the worse in familial adenomatous
      polyposis (FAP) because these patients harbor selected germline APC mutations.
      Colon cancer in the context of FAP can be thought of as occurring "one hit
      quicker" than in the sporadic setting. We were able to isolate and estimate the
      rate of the initiating APC mutation in sporadic cases using the age incidence of
      FAP to approximate the time taken for a cell lineage in a sporadic patient with
      one APC mutation to present clinically as a cancer. Our result of approximately
      10(-5) mutations per allele per year, although higher than previous estimates,
      appears to be consistent with the mutational spectrum of APC. The quality of fit
      provided by this method supports the theory that FAP and sporadic bowel cancer
      follow the same genetic pathway and are separated by only one mutation.

PMID- 18321997
TI  - Heterogeneity of human macrophages in culture and in atherosclerotic plaques.
AB  - Research suggests that monocytes differentiate into unique lineage-determined
      macrophage subpopulations in response to the local cytokine environment. The
      present study evaluated the atherogenic potential of two divergent lineage
      determined human monocyte-derived macrophage subpopulations. Monocytes were
      differentiated for 7 days in the presence of alternative macrophage development
      cytokines: granulocyte-macrophage colony-stimulating factor to produce
      granulocyte-macrophage-CSF macrophages (GM-Mac), or macrophage colony-stimulating
      factor (M-CSF) to produce M-Mac. Gene chip analyses of three monocyte donors
      demonstrated differential expression of inflammatory and cholesterol homeostasis
      genes in the macrophage subpopulations. Quantitative PCR confirmed a fivefold
      elevation in the expression of genes that promote reverse cholesterol transport
      (PPAR-gamma, LXR-alpha, and ABCG1) and macrophage emigration from lesions (CCR7)
      in GM-Mac compared to that in M-Mac. Immunocytochemistry confirmed enhanced
      expression of the proinflammatory marker CD14 in M-Mac relative to GM-Mac. M-Mac
      spontaneously accumulated cholesterol when incubated with unmodified low-density
      lipoprotein whereas GM-Mac only accumulated similar levels of cholesterol after
      protein kinase C activation. Immunostained human coronary arteries showed that
      macrophages with similar antigen expression to that of M-Mac (CD68(+)/CD14(+))
      were predominant within atherosclerotic lesions whereas macrophages with antigen
      expression similar to GM-Mac (CD68(+)/CD14(-)) were predominant in areas devoid
      of disease. The identification of macrophage subpopulations with different gene
      expression patterns and, thus, different potentials for promoting atherosclerosis
      has important experimental and clinical implications and could prove to be a
      valuable finding in developing therapeutic interventions in diseases dependent on
      macrophage function.

PMID- 18321999
TI  - Liver repopulation and carcinogenesis: two sides of the same coin?
AB  - Liver repopulation by transplanted normal hepatocytes has been described in a
      number of experimental settings. Extensive repopulation can also occur from the
      selective proliferation of endogenous normal hepatocytes, both in experimental
      animals and in the human liver. This review highlights the intriguing association
      between clinical and experimental conditions related to liver repopulation and an
      increased risk for development of hepatocellular carcinoma. It is suggested that
      any microenvironment that is able to sustain the clonal growth of normal
      transplanted (or endogenous) hepatocytes is also geared to select for the
      emergence of rare resistant cells with an altered phenotype. Whereas the first
      pathway leads to liver repopulation with normal histology, the latter results in
      the growth of focal proliferative lesions and carries an increased risk of
      neoplastic disease. The implications of this association are discussed, both in
      terms of pathogenetic significance and possible therapeutic exploitation.

PMID- 18322000
TI  - Glucocorticoid-induced tumor necrosis factor receptor-related (GITR)-Fc fusion
      protein inhibits GITR triggering and protects from the inflammatory response
      after spinal cord injury.
AB  - Glucocorticoid-induced tumor necrosis factor receptor-related (GITR) protein is a
      costimulatory molecule that plays a role in inflammation so that GITR-Fc fusion
      protein can exert an anti-inflammatory effect. To investigate the mechanism by
      which GITR-Fc exerts its effects, we first used GITR knock-out (GITR(-/-)) mice
      to verify whether GITR ligand (GITRL)/GITR system played a pro-inflammatory role
      in the spinal cord injury (SCI) model. It is noteworthy that less pronounced
      disease was induced in GITR(-/-) compared with GITR(+/+) mice. We then evaluated
      the effect of GITR-Fc fusion protein against SCI-induced injuries in GITR(-/-)
      and wild-type (GITR(+/+)) mice. Administration of GITR-Fc ameliorated SCI-induced
      inflammation in GITR(+/+) mice as evaluated through: 1) histological damage and
      apoptosis, 2) modulation of apoptosis-related transduction factors (Bax and Bcl
      2), 3) expression of inflammatory markers [nitrotyrosine, inducible nitric-oxide
      synthase, interleukin (IL)-2, IL-12, and tumor necrosis factor-alpha], and 4) T
      lymphocyte infiltration. GITR-Fc was effective in GITR(+/+) but not in GITR(-/-),
      suggesting that in this experimental model, its anti-inflammatory action was due
      to inhibition of GITR triggering and not to GITRL activation. In conclusion, GITR
      plays a role in SCI, and administration of GITR-Fc results in amelioration of SCI
      severity, prompting further studies on the potential anti-inflammatory properties
      of GITR-Fc.

PMID- 18322001
TI  - Modulation of olfactory information processing in the antennal lobe of Manduca
      sexta by serotonin.
AB  - The nervous system copes with variability in the external and internal
      environment by using neuromodulators to adjust the efficacy of neural circuits.
      The role of serotonin (5HT) as a neuromodulator of olfactory information
      processing in the antennal lobe (AL) of Manduca sexta was examined using
      multichannel extracellular electrodes to record the responses of ensembles of AL
      neurons to olfactory stimuli. In one experiment, the effects of 5HT on the
      concentration-response functions for two essential plant oils across a range of
      stimulus intensities were examined. In a second experiment, the effect of 5HT on
      the ability of ensembles to discriminate odorants from different chemical classes
      was examined. Bath application of 5HT enhanced AL unit responses by increasing
      response duration and firing rate, which in turn increased the amount of spike
      time cross-correlation and -covariance between pairs of units. 5HT had the
      greatest effect on overall ensemble activation at higher odorant concentrations,
      resulting in an increase in the gain of the dose-response function of individual
      units. Additionally, response thresholds shifted to lower odorant concentrations
      for some units, suggesting that 5HT increased their sensitivity. Serotonin
      enhanced ensemble discrimination of different concentrations of individual
      odorants as well as discrimination of structurally dissimilar odors at the same
      concentration. Given the known circadian fluctuations of 5HT in the AL of this
      species, these findings support the hypothesis that 5HT periodically enhances
      sensitivity and responsiveness in the AL of Manduca to maximize efficiency when
      the requirement for olfactory acuity is the greatest.

PMID- 18322002
TI  - Neural coding of global form in the human visual cortex.
AB  - Extensive psychophysical and computational work proposes that the perception of
      coherent and meaningful structures in natural images relies on neural processes
      that convert information about local edges in primary visual cortex to complex
      object features represented in the temporal cortex. However, the neural basis of
      these mid-level vision mechanisms in the human brain remains largely unknown.
      Here, we examine functional MRI (fMRI) selectivity for global forms in the human
      visual pathways using sensitive multivariate analysis methods that take advantage
      of information across brain activation patterns. We use Glass patterns,
      parametrically varying the perceived global form (concentric, radial,
      translational) while ensuring that the local statistics remain similar. Our
      findings show a continuum of integration processes that convert selectivity for
      local signals (orientation, position) in early visual areas to selectivity for
      global form structure in higher occipitotemporal areas. Interestingly, higher
      occipitotemporal areas discern differences in global form structure rather than
      low-level stimulus properties with higher accuracy than early visual areas while
      relying on information from smaller but more selective neural populations
      (smaller voxel pattern size), consistent with global pooling mechanisms of local
      orientation signals. These findings suggest that the human visual system uses a
      code of increasing efficiency across stages of analysis that is critical for the
      successful detection and recognition of objects in complex environments.

PMID- 18322003
TI  - Discharge variability of motor units in an intrinsic muscle of transplanted hand.
AB  - The study analyzed the discharge characteristics of the motor units in an
      intrinsic muscle of a transplanted hand. Multichannel electromyographic (EMG)
      recordings were obtained in 11 experimental sessions over 16 mo starting from day
      205 after a hand was transplanted in a 35-yr-old man who had lost his right hand
      22 yr earlier. The action potentials discharged by single motor units were
      identified from the surface EMG signals of the abductor digiti minimi muscle in
      the transplanted hand as the individual performed 60-s maximal and linearly
      increasing (ramp) contractions. Discharge rate decreased from 27.1 +/- 8.4 pulses
      per second (pps) at the start of the maximal contractions to 17.2 +/- 2.9 pps at
      the end (P < 0.001) and increased from 17.4 +/- 4.3 to 22.1 +/- 5.0 pps during
      the ramp contractions (P < 0.05). The SD of the interspike interval (ISI) nearly
      related to the mean ISI with a similar regression slope for the maximal (0.49 +/-
      0.09) and ramp contractions (0.43 +/- 0.10). The coefficient of variation for ISI
      was higher than values in able-bodied persons and did not change during either
      the maximal (36.8 +/- 10.8%) or the ramp contractions (35.9 +/- 7.4%). High
      frequency bursts of activity with <20 ms between two and six action potentials
      occurred during both maximal and ramp contractions. In conclusion, motor neurons
      that reinnervated a muscle in a transplanted hand discharged action potentials
      with a high degree of variability that suggested greater synaptic noise during
      the voluntary contractions.

PMID- 18322004
TI  - Calcium- and calmodulin-dependent inactivation of calcium channels in inner hair
      cells of the rat cochlea.
AB  - Modulation of voltage-gated calcium channels was studied in inner hair cells
      (IHCs) in an ex vivo preparation of the apical turn of the rat organ of Corti.
      Whole cell voltage clamp in the presence of potassium channel blockers showed
      inward calcium currents with millisecond activation and deactivation kinetics.
      When temperature was raised from 22 to 37 degrees C, the calcium currents of
      immature IHCs [<12 days postnatal (P12)] increased threefold in amplitude, and
      developed more pronounced inactivation. This was determined to be calcium
      dependent inactivation (CDI) on the basis of its reliance on external calcium
      (substitution with barium), sensitivity to internal calcium-buffering, and
      voltage dependence (reflecting the calcium driving force). After the onset of
      hearing at P12, IHC calcium current amplitude and the extent of inactivation were
      greatly reduced. Although smaller than in prehearing IHCs, CDI remained
      significant in the mature IHC near the resting membrane potential. CDI in mature
      IHCs was enhanced by application of the endoplasmic calcium pump blocker, benzo
      hydroquinone. Conversely, CDI in immature IHCs was reduced by calmodulin
      inhibitors. Thus voltage-gated calcium channels in mammalian IHCs are subject to
      a calmodulin-mediated process of CDI. The extent of CDI depends on the balance of
      calcium buffering mechanisms and may be regulated by calmodulin-specific
      processes. CDI provides a means for the rate of spontaneous transmitter release
      to be adjusted to variations in hair cell resting potential and steady state
      calcium influx.

PMID- 18322005
TI  - Acquisition of the temporal and ordinal structure of movement sequences in
      incidental learning.
AB  - We investigated the acquisition and integration of temporal and ordinal sequence
      information in an incidental learning model of motor skill acquisition (the
      serial reaction time task). Human participants were exposed to a stimulus
      response sequence that had temporal structure, ordinal structure, or both. By
      changing the temporal or ordinal structure, or both, we were able to ask two
      questions: first, does a regular temporal structure facilitate learning of an
      ordinal sequence and second, is a temporal sequence, presented in the context of
      a random ordinal sequence of finger movements, "picked up" through incidental
      learning? We found that a predictable temporal structure greatly facilitated the
      learning of an ordinal sequence but was not learned when presented in isolation.
      The results suggest that when motor skills are acquired under incidental learning
      conditions, timing is represented at a level specific to the ordinal sequence of
      movements rather than as an independent temporal template.

PMID- 18322006
TI  - Regulation of cholinergic phenotype in developing neurons.
AB  - Specification of neurotransmitter phenotype is critical for neural circuit
      development and is influenced by intrinsic and extrinsic factors. Recent findings
      in rat hypothalamus in vitro suggest the role of neurotransmitter glutamate in
      the regulation of cholinergic phenotype. Here we extended our previous studies on
      the mechanisms of glutamate-dependent regulation of cholinergic phenotypic
      properties in hypothalamic neurons. Using immunocytochemistry, electrophysiology,
      and calcium imaging, we demonstrate that hypothalamic expression of choline
      acetyltransferase (the cholinergic marker) and responsiveness of neurons to
      acetylcholine (ACh) receptor agonists increase during chronic administration of
      an N-methyl-D-aspartate receptor (NMDAR) blocker, MK-801, in developing rats in
      vivo and genetic and pharmacological inactivation of NMDARs in mouse and rat
      developing neuronal cultures. In hypothalamic cultures, an inactivation of NMDA
      receptors also induces ACh-dependent synaptic activity, as do inactivations of
      PKA, ERK/MAPK, CREB, and NF-kappaB, which are known to be regulated by NMDA
      receptors. Interestingly, the increase in cholinergic properties in developing
      neurons that is induced by NMDAR blockade is prevented by the blockade of ACh
      receptors, suggesting that function of ACh receptor is required for the
      cholinergic up-regulation. Using dual recording of monosynaptic excitatory
      postsynaptic currents, we further demonstrate that chronic inactivation of
      ionotropic glutamate receptors induces the cholinergic phenotype in a subset of
      glutamatergic neurons. The phenotypic switch is partial as ACh and glutamate are
      coreleased. The results suggest that developing neurons may not only coexpress
      multiple transmitter phenotypes, but can also change the phenotypes following
      changes in signaling in neuronal circuits.

PMID- 18322007
TI  - Changes in granule cell firing rates precede locally recorded spontaneous
      seizures by minutes in an animal model of temporal lobe epilepsy.
AB  - Although much is known about persistent molecular, cellular, and circuit changes
      associated with temporal lobe epilepsy, mechanisms of seizure onset remain
      unclear. The dentate gyrus displays many persistent epilepsy-related
      abnormalities and is in the mesial temporal lobe where seizures initiate in
      patients. However, little is known about seizure-related activity of individual
      neurons in the dentate gyrus. We used tetrodes to record action potentials of
      multiple, single granule cells before and during spontaneous seizures in
      epileptic pilocarpine-treated rats. Subsets of granule cells displayed four
      distinct activity patterns: increased firing before seizure onset, decreased
      firing before seizure onset, increased firing only after seizure onset, and
      unchanged firing rates despite electrographic seizure activity in the immediate
      vicinity. No cells decreased firing rate immediately after seizure onset. During
      baseline periods between seizures, action potential waveforms and firing rates
      were similar among the four subsets of granule cells in epileptic rats and in
      granule cells of control rats. The mean normalized firing rate of granule cells
      whose firing rates increased before seizure onset deviated from baseline
      earliest, beginning 4 min before dentate gyrus electrographic seizure onset, and
      increased progressively, more than doubling by seizure onset. It is generally
      assumed that neuronal firing rates increase abruptly and synchronously only when
      electrographic seizures begin. However, these findings show heterogeneous and
      gradually building changes in activity of individual granule cells minutes before
      spontaneous seizures.

PMID- 18322008
TI  - Structural inference of native and partially folded RNA by high-throughput
      contact mapping.
AB  - The biological behaviors of ribozymes, riboswitches, and numerous other
      functional RNA molecules are critically dependent on their tertiary folding and
      their ability to sample multiple functional states. The conformational
      heterogeneity and partially folded nature of most of these states has rendered
      their characterization by high-resolution structural approaches difficult or even
      intractable. Here we introduce a method to rapidly infer the tertiary helical
      arrangements of large RNA molecules in their native and non-native solution
      states. Multiplexed hydroxyl radical (.OH) cleavage analysis (MOHCA) enables the
      high-throughput detection of numerous pairs of contacting residues via random
      incorporation of radical cleavage agents followed by two-dimensional gel
      electrophoresis. We validated this technology by recapitulating the unfolded and
      native states of a well studied model RNA, the P4-P6 domain of the Tetrahymena
      ribozyme, at subhelical resolution. We then applied MOHCA to a recently
      discovered third state of the P4-P6 RNA that is stabilized by high concentrations
      of monovalent salt and whose partial order precludes conventional techniques for
      structure determination. The three-dimensional portrait of a compact, non-native
      RNA state reveals a well ordered subset of native tertiary contacts, in contrast
      to the dynamic but otherwise similar molten globule states of proteins. With its
      applicability to nearly any solution state, we expect MOHCA to be a powerful tool
      for illuminating the many functional structures of large RNA molecules and
      RNA/protein complexes.

PMID- 18322009
TI  - RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast
      differentiation.
AB  - NF-kappaB inducing kinase (NIK) is required for osteoclastogenesis in response to
      pathologic stimuli, and its loss leads to functional blockade of both alternative
      and classical NF-kappaB caused by cytoplasmic retention by p100. We now show that
      deletion of p100 restores the capacity of NIK-deficient osteoclast (OC)
      precursors to differentiate and normalizes RelB and p65 signaling.
      Differentiation of NIK-/- precursors is also restored by overexpression of RelB,
      but not p65. Additionally, RelB-/- precursors fail to form OCs in culture, and
      this defect is rescued by re-expression of RelB, but not by overexpression of
      p65. To further support the role of RelB in OCs, we challenged RelB-/- mice with
      TNF-alpha in vivo and found a diminished osteoclastogenic response. We then
      examined tumor-induced osteolysis in both RelB-/- and NIK-/- mice by using the
      B16 melanoma model. Growth of tumor cells in the bone marrow was similar to WT
      controls, but the absence of either RelB or NIK completely blocked the tumor
      induced loss of trabecular bone. Thus, the alternative NF-kappaB pathway,
      culminating in activation of RelB, has a key and specific role in the
      differentiation of OCs that cannot be compensated for by p65.

PMID- 18322010
TI  - Heat stress causes inhibition of the de novo synthesis of antenna proteins and
      photobleaching in cultured Symbiodinium.
AB  - Coral bleaching, caused by heat stress, is accompanied by the light-induced loss
      of photosynthetic pigments in in situ symbiotic dinoflagellate algae
      (Symbiodinium spp.). However, the molecular mechanisms responsible for pigment
      loss are poorly understood. Here, we show that moderate heat stress causes
      photobleaching through inhibition of the de novo synthesis of intrinsic light
      harvesting antennae [chlorophyll a-chlorophyll c(2)-peridinin-protein complexes
      (acpPC)] in cultured Symbiodinium algae and that two Clade A Symbiodinium species
      showing different thermal sensitivities of photobleaching also show differential
      sensitivity of this key protein synthesis process. Photoinhibition of photosystem
      II (PSII) and subsequent photobleaching were observed at temperatures of >31
      degrees C in cultured Symbiodinium CS-73 cells grown at 25-34 degrees C, but not
      in cultures of the more thermally tolerant control Symbiodinium species OTcH-1.
      We found that bleaching in CS-73 is associated with loss of acpPC, which is a
      major antennae protein in Symbiodinium. In addition, the thermally induced loss
      of this protein is light-dependent, but does not coincide directly with PSII
      photoinhibition and is not caused by stimulated degradation of acpPC. In cells
      treated at 34 degrees C over 24 h, the steady-state acpPC mRNA pool was modestly
      reduced, by approximately 30%, whereas the corresponding synthesis rate of acpPC
      was diminished by >80%. Our results suggest that photobleaching in Symbiodinium
      is consequentially linked to the relative susceptibility of PSII to
      photoinhibition during thermal stress and occurs, at least partially, because of
      the loss of acpPC via undefined mechanism(s) that hamper the de novo synthesis of
      acpPC primarily at the translational processing step.

PMID- 18322011
TI  - Does antisense make sense of AID targeting?

PMID- 18322012
TI  - Nucleoprotein structure of the CD4 locus: implications for the mechanisms
      underlying CD4 regulation during T cell development.
AB  - The CD4 gene is regulated in a stage-specific manner during T cell development,
      being repressed in CD4(-)CD8(-) double-negative (DN) and CD8 cells, but expressed
      in CD4(+)CD8(+) double-positive (DP) and CD4 cells. Furthermore, the
      expression/repression pattern is reversible in developing (DN and DP) thymocytes,
      but irreversible in mature (CD4 and CD8) T cells. Here, we explored the molecular
      mechanisms underlying this complex mode of regulation by examining the
      nucleoprotein structure of the CD4 locus throughout T cell development and in DN
      cells lacking the CD4 silencer. In DN cells, the CD4 enhancer is preloaded with
      multiple transcription activators, but p300 recruitment is impaired by the
      silencer that is associated with the repressor Runx1. DP cells achieve high-level
      CD4 expression via a combination of CD4 derepression and true activation, but
      Runx1 remains bound to the silencer that retains an open chromatin configuration.
      In CD4 cells, Runx1 dissociates from the silencer that has become less
      accessible, and CD4 transcription appears to be achieved via a mechanism distinct
      from that operating in DP cells. In CD8 cells, the CD4 promoter becomes
      incorporated into heterochromatin-like structure. Our data shed light on the
      molecular basis of CD4 regulation and provide a conceptual framework for
      understanding how the same regulatory elements can mediate both reversible and
      irreversible CD4 regulation.

PMID- 18322013
TI  - The maturing architecture of the brain's default network.
AB  - In recent years, the brain's "default network," a set of regions characterized by
      decreased neural activity during goal-oriented tasks, has generated a significant
      amount of interest, as well as controversy. Much of the discussion has focused on
      the relationship of these regions to a "default mode" of brain function. In early
      studies, investigators suggested that, the brain's default mode supports "self
      referential" or "introspective" mental activity. Subsequently, regions of the
      default network have been more specifically related to the "internal narrative,"
      the "autobiographical self," "stimulus independent thought," "mentalizing," and
      most recently "self-projection." However, the extant literature on the function
      of the default network is limited to adults, i.e., after the system has reached
      maturity. We hypothesized that further insight into the network's functioning
      could be achieved by characterizing its development. In the current study, we
      used resting-state functional connectivity MRI (rs-fcMRI) to characterize the
      development of the brain's default network. We found that the default regions are
      only sparsely functionally connected at early school age (7-9 years old); over
      development, these regions integrate into a cohesive, interconnected network.

PMID- 18322014
TI  - Txnip balances metabolic and growth signaling via PTEN disulfide reduction.
AB  - Thioredoxin-interacting protein (Txnip) inhibits thioredoxin NADPH-dependent
      reduction of protein disulfides. Total Txnip knockout (TKO) mice adapted
      inappropriately to prolonged fasting by shifting fuel dependence of skeletal
      muscle and heart from fat and ketone bodies to glucose. TKO mice exhibited
      increased Akt signaling, insulin sensitivity, and glycolysis in oxidative tissues
      (skeletal muscle and hearts) but not in lipogenic tissues (liver and adipose
      tissue). The selective activation of Akt in skeletal muscle and hearts was
      associated with impaired mitochondrial fuel oxidation and the accumulation of
      oxidized (inactive) PTEN, whose activity depends on reduction of two critical
      cysteine residues. Whereas muscle- and heart-specific Txnip knockout mice
      recapitulated the metabolic phenotype exhibited by TKO mice, liver-specific Txnip
      knockout mice were similar to WT mice. Embryonic fibroblasts derived from
      knockout mice also accumulated oxidized (inactive) PTEN and had elevated Akt
      phosphorylation. In addition, they had faster growth rates and increased
      dependence on anaerobic glycolysis due to impaired mitochondrial fuel oxidation,
      and they were resistant to doxorubicin-facilitated respiration-dependent
      apoptosis. In the absence of Txnip, oxidative inactivation of PTEN and subsequent
      activation of Akt attenuated mitochondrial respiration, resulting in the
      accumulation of NADH, a competitive inhibitor of thioredoxin NADPH-reductive
      activation of PTEN. These findings indicate that, in nonlipogenic tissues, Txnip
      is required to maintain sufficient thioredoxin NADPH activity to reductively
      reactivate oxidized PTEN and oppose Akt downstream signaling.

PMID- 18322015
TI  - A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing
      antibodies.
AB  - Most antibodies induced by HIV-1 are ineffective at preventing initiation or
      spread of infection because they are either nonneutralizing or narrowly isolate
      specific. Rare, "broadly neutralizing" antibodies have been detected that
      recognize relatively conserved regions on the envelope glycoprotein. Using
      stringently characterized, homogeneous preparations of trimeric HIV-1 envelope
      protein in relevant conformations, we have analyzed the molecular mechanism of
      neutralization by two of these antibodies, 2F5 and 4E10. We find that their
      epitopes, in the membrane-proximal segment of the envelope protein ectodomain,
      are exposed only on a form designed to mimic an intermediate state during viral
      entry. These results help explain the rarity of 2F5- and 4E10-like antibody
      responses and suggest a strategy for eliciting them.

PMID- 18322016
TI  - Thioredoxin-mediated reversible dissociation of a stromal multiprotein complex in
      response to changes in light availability.
AB  - A Calvin cycle multiprotein complex including phosphoribulokinase (PRK),
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and a small protein, CP12, has
      previously been identified. In this article, we have studied this complex in
      leaves and have shown that dissociation and reassociation of the PRK/GAPDH/CP12
      complex occurs in a time frame of minutes, allowing for rapid regulation of
      enzyme activity. Furthermore, we have shown that the extent of formation and
      dissociation of the PRK/GAPDH/CP12 complex correlates with the quantity of light.
      These data provide evidence linking the status of this complex with the rapid and
      subtle regulation of GAPDH and PRK activities in response to fluctuations in
      light availability. We have also demonstrated that dissociation of this complex
      depends on electron transport chain activity and that the major factor involved
      in the dissociation of the pea complex was thioredoxin f. We show here that both
      PRK and GAPDH are present in the reduced form in leaves in the dark, but are
      inactive, demonstrating the role of the PRK/GAPDH/CP12 complex in deactivating
      these enzymes in response to reductions in light intensity. Based on our data, we
      propose a model for thioredoxin f-mediated activation of PRK and GAPDH by two
      mechanisms: directly through reduction of disulfide bonds within these enzymes
      and indirectly by mediating the breakdown of the complex in response to changes
      in light intensity.

PMID- 18322017
TI  - Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium
      and water-transporting proteins.
AB  - Bartter's syndrome represents a group of hereditary salt- and water-losing renal
      tubulopathies caused by loss-of-function mutations in proteins mediating or
      regulating salt transport in the thick ascending limb (TAL) of Henle's loop.
      Mutations in the ROMK channel cause type II antenatal Bartter's syndrome that
      presents with maternal polyhydramnios and postnatal life-threatening volume
      depletion. We have developed a colony of Romk null mice showing a Bartter-like
      phenotype and with increased survival to adulthood, suggesting the activation of
      compensatory mechanisms. To test the hypothesis that upregulation of Na(+)
      transporting proteins in segments distal to the TAL contributes to compensation,
      we studied expression of salt-transporting proteins in ROMK-deficient (Romk(-/-))
      mice. Plasma aldosterone was 40% higher and urinary PGE(2) excretion was 1.5-fold
      higher in Romk(-/-) compared with wild-type littermates. Semiquantitative
      immunoblotting of kidney homogenates revealed decreased abundances of proximal
      tubule Na(+)/H(+) exchanger (NHE3) and Na(+)-P(i) cotransporter (NaPi-IIa) and
      TAL-specific Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2/BSC1) in Romk(-/-) mice,
      while the distal convoluted tubule (DCT)-specific Na(+)-Cl(-) cotransporter
      (NCC/TSC) was markedly increased. The abundance of the alpha-,beta-, and gamma
      subunits of the epithelial Na(+) channel (ENaC) was slightly increased, although
      only differences for gamma-ENaC reached statistical significance. Morphometry
      revealed a fourfold increase in the fractional volume of DCT but not of
      connecting tubule (CNT) and collecting duct (CCD). Consistently, CNT and CD of
      Romk(-/-) mice revealed no apparent increase in the luminal abundance of the ENaC
      compared with those of wild-type mice. These data suggest that the loss of ROMK
      dependent Na(+) absorption in the TAL is compensated predominately by
      upregulation of Na(+) transport in downstream DCT cells. These adaptive changes
      in Romk(-/-) mice may help to limit renal Na(+) loss, and thereby, contribute to
      survival of these mice.

PMID- 18322018
TI  - Sensitization of pelvic afferent nerves in the in vitro rat urinary bladder
      pelvic nerve preparation by purinergic agonists and cyclophosphamide
      pretreatment.
AB  - Effects of purinergic agonists (alpha,beta-meATP and ATP) and cyclophosphamide
      induced cystitis on bladder afferent nerve (BAN) activity were studied in an in
      vitro bladder-pelvic nerve preparation. Distension of the bladder induced
      spontaneous bladder contractions that were accompanied by multiunit afferent
      firing. Intravesical administration of 40 and 130 microM alpha,beta-meATP
      increased afferent firing from 27 +/- 3 to 53 +/- 6 and 61 +/- 2 spikes/s,
      respectively, but did not change the maximum amplitude of spontaneous bladder
      contractions. Electrical stimulation on the surface of the bladder elicited
      action potentials (AP) in BAN. alpha,beta-meATP decreased the voltage threshold
      from 9.0 +/- 1.2 to 3.5 +/- 0.5 V (0.15-ms pulse duration) and increased the area
      of the APs (82% at 80-V stimulus intensity). These effects were blocked by TNP
      ATP (30 microM). ATP (2 mM) applied in the bath produced similar changes in BAN
      activity. These effects were blocked by bath application of PPADS (30 microM).
      Neither TNP-ATP nor PPADS affected BAN activity induced by distension of the
      bladder. Cystitis induced by pretreatment of the rats with cyclophosphamide (100
      mg/kg ip) increased afferent firing in response to isotonic bladder distension
      (10-40 cmH(2)O), decreased the threshold, and increased the area of evoked APs.
      The increase in afferent firing at 10 cmH(2)O intravesical pressure was reduced
      52% by PPADS. These results indicate that purinergic agonists acting on P2X
      receptors and cystitis induced by cyclophosphamide can increase excitability of
      the BANs.

PMID- 18322019
TI  - Loss of prostaglandin E2 release from immortalized urothelial cells obtained from
      interstitial cystitis patient bladders.
AB  - Interstitial cystitis (IC) is associated with increased activated mast cell
      numbers in the bladder and impairment of the barrier function of the urothelium.
      We stimulated immortalized urothelial cells derived from the inflamed region of
      IC bladders (SR22A or SM28 abn) or from healthy bladders (PD07i or PD08i) with
      tryptase and measured phospholipase A(2) (PLA(2)) activity and the resultant
      release of arachidonic acid and prostaglandin E(2) (PGE(2)). Tryptase stimulation
      of either PD07i or SR22A resulted in similar increases in PLA(2) activity and
      arachidonic acid release. However, tryptase stimulation of SR22A and SM28 abn did
      not result in a significant increase in PGE(2) release compared with the increase
      in PGE(2) release from tryptase-stimulated PD07i and PD08i cells. Expression of
      mRNA for cyclooxygenase-2 and PGE synthase was lower and mRNA for 15
      hydroxyprostaglandin dehydrogenase was higher in SR22A compared with PD07i,
      suggesting that both decreased synthesis and increased metabolism are responsible
      for the lack of a PGE(2) response in tryptase-stimulated SR22A cells. Since
      PGE(2) is a cytoprotective eicosanoid, the failure to produce this metabolite in
      cells isolated from the IC bladder may represent an increased susceptibility to
      damage by proinfammatory stimuli.

PMID- 18322020
TI  - LOX-1 and inflammation: a new mechanism for renal injury in obesity and diabetes.
AB  - The early nephropathy in obese, diabetic, dyslipidemic (ZS) rats is characterized
      by tubular lipid accumulation and pervasive inflammation, two critically
      interrelated events. We now tested the hypothesis that proximal tubules from ZS
      obese diabetic rats in vivo, and proximal tubule cells (NRK52E) exposed to
      oxidized LDL (oxLDL) in vitro, change their normally quiescent epithelial
      phenotype into a proinflammatory phenotype. Urine of obese diabetic rats
      contained more lipid peroxides, and LOX-1, a membrane receptor that internalizes
      oxidized lipids, was mobilized to luminal sites. Levels of ICAM-1 and focal
      adhesion kinase, which participate in leukocyte migration and epithelial
      dedifferentiation, respectively, were also upregulated in tubules. NRK52E cells
      exposed to oxLDL showed similar modifications, plus suppression of anti
      inflammatory transcription factor peroxisome proliferator-activated receptor
      delta. In addition, oxLDL impaired epithelial barrier function. These alterations
      were prevented by an anti-LOX-1 antibody. The data support the concept that
      tubular LOX-1 activation driven by lipid oxidants in the preurine fluid is
      critical in the inflammatory changes. We suggest that luminal lipid oxidants and
      abnormal tubular permeability may be partly responsible for the renal
      tubulointerstitial injury of obesity, diabetes, and dyslipidemia.

PMID- 18322021
TI  - Anti-inflammatory effects of pigment epithelium-derived factor in diabetic
      nephropathy.
AB  - Previously, we have reported that pigment epithelium-derived factor (PEDF)
      ameliorates albuminuria and inhibits matrix protein deposition in the kidney of
      streptozotocin (STZ)-induced diabetic rats, suggesting a renoprotective effect of
      PEDF in early stages of diabetic nephropathy. As inflammation is a major
      contributor to the development and progression of diabetic nephropathy, we
      examined in the present study whether PEDF inhibits renal inflammation in
      diabetic kidney. Diabetic rats received an intravenous injection of an adenovirus
      expressing PEDF (Ad-PEDF) or the same titer of a control virus. Three wk after
      the injection, diabetic rats treated with the control virus showed significantly
      elevated renal levels of proinflammatory factors such as ICAM-1, MCP-1, TNF
      alpha, and VEGF compared with age-matched nondiabetic controls. Ad-PEDF
      effectively suppressed the overexpression of these proinflammatory factors in
      diabetic kidneys. In cultured primary human renal mesangial cells (HMC), the high
      glucose medium-induced upregulation of VEGF and MCP-1 was largely blocked by
      PEDF. Furthermore, PEDF inhibited high glucose-induced activation of NF-kappaB, a
      key transcription factor mediating inflammatory responses, and hypoxia-inducible
      factor-1, a major activator of VEGF expression in HMC. These results suggest that
      the renoprotective effect of PEDF against diabetic nephropathy may be partially
      through its anti-inflammatory activity, likely by blocking the NF-kappaB and HIF
      1 pathways.

PMID- 18322022
TI  - Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and
      reduce surface expression and function of the epithelial sodium channel.
AB  - We previously reported the existence of multiple isoforms of human Nedd4-2 (Am J
      Physiol Renal Physiol 285: F916-F929, 2003). When overexpressed in M-1 collecting
      duct epithelia, full-length Nedd4-2 (Nedd4-2), Nedd4-2 lacking the NH(2)-terminal
      C2 domain (Nedd4-2DeltaC2), and Nedd4-2 lacking WW domains 2 and 3 (Nedd4
      2DeltaWW2,3) variably reduce benzamil-sensitive Na(+) transport. We investigated
      the effect of each of the Nedd4-2 isoforms on cell surface expression and
      ubiquitination of ENaC subunits. We find that alphaENaC when transfected alone or
      with beta and gammaENaC is expressed at the cell surface and this membrane
      expression is variably reduced by coexpression with each of the Nedd4-2 isoforms.
      Nedd4-2 reduces the half-life of ENaC subunits and enhances the ubiquitination of
      alpha, beta, and gammaENaC subunits when expressed alone or together suggesting
      that each subunit is a target for Nedd4-2-mediated ubiquitination. As has been
      reported recently, we confirm that the surface-expressed pool of ENaC is multi
      ubiquitinated. Inhibitors of the proteasome increase ubiquitination of ENaC
      subunits and stimulate Na(+) transport in M-1 cells consistent with a role for
      the ubiquitin-proteasome pathway in regulating Na(+) transport in the collecting
      duct.

PMID- 18322023
TI  - Mesenchymal transition in kidney collecting duct epithelial cells.
AB  - Progressive organ damage due to tissue scarring and fibrosis is a paradigm shared
      by numerous human diseases including chronic kidney disease. The purpose of this
      study was to confirm the hypothesis that collecting duct (CD) epithelial cells
      can undergo mesenchymal transition (EMT) in vitro. The mechanism by which CDs
      undergo EMT is complex and involves both early and late cellular events. Early
      events include rapid insulin-like growth factor (IGF)-induced Akt and GSK-3beta
      phosphorylation, associated with early disruption of E-cadherin-beta-catenin
      membrane colocalization, with translocation of E-cadherin to endosomes, with
      translocation of beta-catenin to the nucleus, and with an increase in Snail
      expression. Transforming growth factor-beta1, on the other hand, induced early
      activation of Smad3 and its translocation to the nucleus, Erk1/2 phosphorylation,
      and early disruption of membrane E-cadherin localization. The late consequences
      of these events included a phenotypic transformation of the cells to a
      mesenchymal morphology with associated increase in vimentin and alpha-smooth
      muscle actin protein expression and a decrease in total cellular E-cadherin
      expression, detectable as early as 24 h after stimulation.

PMID- 18322024
TI  - Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone.
AB  - The activity of the Na(+)/H(+) exchanger NHE3 is regulated by a number of factors
      including parathyroid hormone (PTH). In the current study, we used a renal
      epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms
      underlying the long-term effects of PTH on NHE3 transport activity and
      expression. We observed that NHE3 activity was reduced 6 h after addition of PTH,
      and this reduction persisted almost unaltered after 24 h. The decrease in
      activity was associated with diminished NHE3 cell surface expression at 6, 16,
      and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3
      mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small,
      but significant, decrease in mRNA stability. Additionally, by analyzing the rat
      NHE3 gene promoter activity in OKP cells, we verified that the regulatory region
      spanning the segment -152 to +55 was mildly reduced under the influence of PTH.
      This effect was completely abolished by the presence of the PKA inhibitor KT
      5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA
      levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small
      reduction of mRNA half-life, and decrease in the total amount of protein which is
      preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression
      is likely to be responsible for the reduction of sodium, bicarbonate, and fluid
      reabsorption in the proximal tubule consistently perceived in experimental models
      of PTH disorders.

PMID- 18322025
TI  - Predicting mortality among a general practice-based sample of older people with
      heart failure.
AB  - OBJECTIVE: To identify factors available to general practitioners (GPs) that are
      predictive of mortality within a general practice-based population of heart
      failure patients, and to report the sensitivity and specificity of prognostic
      information from GPs. METHODS: Five hundred and forty-two heart failure patients
      aged >60 years were recruited from 16 UK GP surgeries. Patients completed quality
      of-life and services use questionnaires every 3 months for 24 months or until
      death. Factors with independent significant association with survival were
      identified using Cox proportional hazards regression analysis. RESULTS: Women had
      a 58% lower risk of death. Patients self-reporting New York Heart Association
      Classification III or IV had an 81% higher risk of death. Patients aged 85+ years
      had over a five-fold risk of death as compared with those aged <65 years.
      Patients with a co-morbidity of cancer had a 78% higher risk of death. Of the 14
      patients who died in a 12-month period, the GPs identified 11 (sensitivity 79%).
      They identified 133 of the 217 who did not die (specificity 61%). DISCUSSION:
      Predictors readily available to GPs, such as patient characteristics, are easy to
      adapt to use in general practice, where most heart failure patients are diagnosed
      and treated. Identifying factors likely to influence death is useful in primary
      care, as this can initiate discussion about end-of-life care.

PMID- 18322026
TI  - Promoting early presentation of breast cancer: development of a psycho
      educational intervention.
AB  - OBJECTIVES: Women who delay presenting with breast cancer have a reduced chance
      of survival. Older women, who are at greater risk of developing breast cancer,
      are more likely to delay presenting with the disease. The aim of this
      developmental work was to design a psycho-educational intervention to promote
      early help-seeking by older women with breast cancer symptoms. We also aimed to
      demonstrate the feasibility of implementing the intervention with women attending
      for their final invited mammogram in the National Health Service (NHS) Breast
      Screening Programme. METHODS: The intervention was designed to address the
      factors associated with delayed presentation by women with breast cancer. These
      risk factors were placed in a theoretical framework to understand patient delay.
      The intervention incorporated behavioural change techniques that, according to
      previous research, have been demonstrated to be effective. RESULTS: The
      intervention was developed in two formats to be delivered by diagnostic
      radiographers: a booklet alone and a brief interview plus the booklet. The
      intervention was acceptable to both older women and healthcare professionals in
      the NHS Breast Screening Programme. DISCUSSION: The intervention will be tested
      ultimately in a multicentre randomized controlled trial to determine whether it
      can reduce the proportion of older women who delay their presentation and thereby
      save lives.

PMID- 18322027
TI  - Education and self-management for people newly diagnosed with type 2 diabetes: a
      qualitative study of patients' views.
AB  - OBJECTIVES: We explored the perceptions, views and experiences of diabetes
      education in people with type 2 diabetes who were participating in a UK
      randomized controlled trial of methods of education. The intervention arm of the
      trial was based on DESMOND, a structured programme of group education sessions
      aimed at enabling self-management of diabetes, while the standard arm was usual
      care from general practices. METHODS: Individual semi-structured interviews were
      conducted with 36 adult patients, of whom 19 had attended DESMOND education
      sessions and 17 had been randomized to receive usual care. Data analysis was
      based on the constant comparative method. RESULTS: Four principal orientations
      towards diabetes and its management were identified: 'resisters', 'identity
      resisters, consequence accepters', 'identity accepters, consequence resisters'
      and 'accepters'. Participants offered varying accounts of the degree of personal
      responsibility that needed to be assumed in response to the diagnosis.
      Preferences for different styles of education were also expressed, with many
      reporting that they enjoyed and benefited from group education, although some
      reported ambivalence or disappointment with their experiences of education. It
      was difficult to identify striking thematic differences between accounts of
      people on different arms of the trial, although there was some very tentative
      evidence that those who attended DESMOND were more accepting of a changed
      identity and its implications for their management of diabetes. DISCUSSION: No
      one single approach to education is likely to suit all people newly diagnosed
      with diabetes, although structured group education may suit many. This paper
      identifies varying orientations and preferences of people with diabetes towards
      forms of both education and self-management, which should be taken into account
      when planning approaches to education.

PMID- 18322028
TI  - The DESMOND educational intervention.

PMID- 18322029
TI  - Empowered to change: evidence from a qualitative exploration of a user-informed
      psycho-educational programme for people with type 1 diabetes.
AB  - OBJECTIVES: To evaluate the impact of a user-informed psycho-educational
      programme for people with type 1 diabetes. METHODS: Qualitative data derived from
      repeated interviews and diaries enabled an appraisal of participants' unique,
      individual experiences. RESULTS: Thematic analysis elicited a number of themes
      from each type of data (interview and diaries) which bore similarities in their
      representation of a process whereby change was desired, solutions were found to
      bring about that change, and then the process was planned or embarked upon.
      DISCUSSION: The acquisition of trustworthy information and a repertoire of coping
      skills accompanied by regular contact with other people with type 1 diabetes
      meant that participants achieved an increased sense of control in their lives and
      were empowered to change.

PMID- 18322030
TI  - Chronic illness, reproductive health and moral work: women's experiences of
      epilepsy.
AB  - BACKGROUND: The impact of chronic illness on families has long been noted in the
      literature, but in such studies families appear as ready-formed entities. This
      exploratory qualitative study addresses the largely unacknowledged work involved
      in the production of families and the maintenance of reproductive health by women
      with epilepsy, a condition whose symptoms and treatment have serious implications
      for all aspects of reproductive health. METHODS: Qualitative in-depth interviews
      were conducted with a sample of 15 women aged 20-40 years diagnosed with epilepsy
      and recruited from across the UK. The women had a range of neurological symptoms
      and hence different diagnostic categories; most had been diagnosed during
      childhood or adolescence. Ten women had at least one child. RESULTS: Women's
      experiences of healthcare services for key phases of reproduction are explored.
      While some women reported that they had received good healthcare, others reported
      that they were given inadequate information and that advice was offered too late
      to enable them to take appropriate action. DISCUSSION: Management of both
      epilepsy and reproductive health involves work with a significant moral
      dimension, the accomplishment of which is contingent on appropriate and timely
      advice from healthcare practitioners.

PMID- 18322031
TI  - The unacknowledged impact of chronic schistosomiasis.
AB  - OBJECTIVES: To summarize new knowledge on the range of disease due to chronic
      schistosomiasis and examine the debilitating burden of both light and heavy
      infection; to outline goals of disease prevention, including current age-targeted
      strategies and more extended programmes aimed at preventing transmission.
      METHODS: A systematic search of 2004-2007 papers via PUBMED and related databases
      using 'schistosom' and disability- or treatment-related subject headings. Reports
      were independently reviewed for inclusion. RESULTS: Sixty-eight papers met review
      objectives. These suggest new evidence for a causative link between schistosome
      infection, antiparasite inflammation, and risk for anaemia, growth stunting and
      undernutrition in affected populations, as well as exacerbation of co-infections
      and impairment of cognitive development and work capacity. Formal quality-of-life
      assessment defines a significant 9.5-24% disability with the most aggressive
      schistosome species, Schistosoma japonicum. DISCUSSION: Schistosomiasis
      represents a serious but under-recognized disease burden for many developing
      countries. Infection (and not intensity of infection) should be considered the
      defining feature of morbidity formation. Links between infection and long-term
      disabilities reduce the chances of combating rural poverty. Changes in our
      appreciation of schistosomiasis-related disease burden means it is no longer
      appropriate to leave infected persons untreated, and newer approaches to control
      should focus on preventing transmission.

PMID- 18322033
TI  - Cohesion group approach for evolutionary analysis of TyrA, a protein family with
      wide-ranging substrate specificities.
AB  - Many enzymes and other proteins are difficult subjects for bioinformatic analysis
      because they exhibit variant catalytic, structural, regulatory, and fusion mode
      features within a protein family whose sequences are not highly conserved.
      However, such features reflect dynamic and interesting scenarios of evolutionary
      importance. The value of experimental data obtained from individual organisms is
      instantly magnified to the extent that given features of the experimental
      organism can be projected upon related organisms. But how can one decide how far
      along the similarity scale it is reasonable to go before such inferences become
      doubtful? How can a credible picture of evolutionary events be deduced within the
      vertical trace of inheritance in combination with intervening events of lateral
      gene transfer (LGT)? We present a comprehensive analysis of a dehydrogenase
      protein family (TyrA) as a prototype example of how these goals can be
      accomplished through the use of cohesion group analysis. With this approach, the
      full collection of homologs is sorted into groups by a method that eliminates
      bias caused by an uneven representation of sequences from organisms whose
      phylogenetic spacing is not optimal. Each sufficiently populated cohesion group
      is phylogenetically coherent and defined by an overall congruence with a distinct
      section of the 16S rRNA gene tree. Exceptions that occasionally are found
      implicate a clearly defined LGT scenario whereby the recipient lineage is
      apparent and the donor lineage of the gene transferred is localized to those
      organisms that define the cohesion group. Systematic procedures to manage and
      organize otherwise overwhelming amounts of data are demonstrated.

PMID- 18322034
TI  - The membrane-proximal external region of the human immunodeficiency virus type 1
      envelope: dominant site of antibody neutralization and target for vaccine design.
AB  - Enormous efforts have been made to produce a protective vaccine against human
      immunodeficiency virus type 1; there has been little success. However, the
      identification of broadly neutralizing antibodies against epitopes on the highly
      conserved membrane-proximal external region (MPER) of the gp41 envelope protein
      has delineated this region as an attractive vaccine target. Furthermore, emerging
      structural information on the MPER has provided vaccine designers with new
      insights for building relevant immunogens. This review describes the current
      state of the field regarding (i) the structure and function of the gp41 MPER;
      (ii) the structure and binding mechanisms of the broadly neutralizing antibodies
      2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In
      addition, emerging approaches to vaccine design are presented.

PMID- 18322035
TI  - Molecular control of bacterial death and lysis.
AB  - Although the phenomenon of bacterial cell death and lysis has been studied for
      over 100 years, the contribution of these important processes to bacterial
      physiology and development has only recently been recognized. Contemporary study
      of cell death and lysis in a number of different bacteria has revealed that these
      processes, once thought of as being passive and unregulated, are actually
      governed by highly complex regulatory systems. An emerging paradigm in this field
      suggests that, analogous to programmed cell death in eukaryotes, regulated cell
      death and lysis in bacteria play an important role in both developmental
      processes, such as competence and biofilm development, and the elimination of
      damaged cells, such as those irreversibly injured by environmental or antibiotic
      stress. Further study in this exciting field of bacterial research may provide
      new insight into the potential evolutionary link between control of cell death in
      bacteria and programmed cell death (apoptosis) in eukaryotes.

PMID- 18322036
TI  - Fe-S cluster assembly pathways in bacteria.
AB  - Iron-sulfur (Fe-S) clusters are required for critical biochemical pathways,
      including respiration, photosynthesis, and nitrogen fixation. Assembly of these
      iron cofactors is a carefully controlled process in cells to avoid toxicity from
      free iron and sulfide. Multiple Fe-S cluster assembly pathways are present in
      bacteria to carry out basal cluster assembly, stress-responsive cluster assembly,
      and enzyme-specific cluster assembly. Although biochemical and genetic
      characterization is providing a partial picture of in vivo Fe-S cluster assembly,
      a number of mechanistic questions remain unanswered. Furthermore, new factors
      involved in Fe-S cluster assembly and repair have recently been identified and
      are expanding the complexity of current models. Here we attempt to summarize
      recent advances and to highlight new avenues of research in the field of Fe-S
      cluster assembly.

PMID- 18322040
TI  - The afterlife for retiring deans and other senior medical administrators.
AB  - Career options for individuals leaving the administrative role as dean of a
      school of medicine or other senior administrative positions are considered.
      Options discussed include retirement and a variety of other positions both within
      schools of medicines and in other venues. Many opportunities exist for a
      challenging and fulfilling career path after leaving the role as a senior
      administrator in an academic medical center.

PMID- 18322039
TI  - Moonlighting proteins in yeasts.
AB  - Proteins able to participate in unrelated biological processes have been grouped
      under the generic name of moonlighting proteins. Work with different yeast
      species has uncovered a great number of moonlighting proteins and shown their
      importance for adequate functioning of the yeast cell. Moonlighting activities in
      yeasts include such diverse functions as control of gene expression, organelle
      assembly, and modification of the activity of metabolic pathways. In this review,
      we consider several well-studied moonlighting proteins in different yeast
      species, paying attention to the experimental approaches used to identify them
      and the evidence that supports their participation in the unexpected function.
      Usually, moonlighting activities have been uncovered unexpectedly, and up to now,
      no satisfactory way to predict moonlighting activities has been found. Among the
      well-characterized moonlighting proteins in yeasts, enzymes from the glycolytic
      pathway appear to be prominent. For some cases, it is shown that despite close
      phylogenetic relationships, moonlighting activities are not necessarily conserved
      among yeast species. Organisms may utilize moonlighting to add a new layer of
      regulation to conventional regulatory networks. The existence of this type of
      proteins in yeasts should be taken into account when designing mutant screens or
      in attempts to model or modify yeast metabolism.

PMID- 18322037
TI  - Bacterial growth and cell division: a mycobacterial perspective.
AB  - The genus Mycobacterium is best known for its two major pathogenic species, M.
      tuberculosis and M. leprae, the causative agents of two of the world's oldest
      diseases, tuberculosis and leprosy, respectively. M. tuberculosis kills
      approximately two million people each year and is thought to latently infect one
      third of the world's population. One of the most remarkable features of the
      nonsporulating M. tuberculosis is its ability to remain dormant within an
      individual for decades before reactivating into active tuberculosis. Thus,
      control of cell division is a critical part of the disease. The mycobacterial
      cell wall has unique characteristics and is impermeable to a number of compounds,
      a feature in part responsible for inherent resistance to numerous drugs. The
      complexity of the cell wall represents a challenge to the organism, requiring
      specialized mechanisms to allow cell division to occur. Besides these
      mycobacterial specializations, all bacteria face some common challenges when they
      divide. First, they must maintain their normal architecture during and after cell
      division. In the case of mycobacteria, that means synthesizing the many layers of
      complex cell wall and maintaining their rod shape. Second, they need to
      coordinate synthesis and breakdown of cell wall components to maintain integrity
      throughout division. Finally, they need to regulate cell division in response to
      environmental stimuli. Here we discuss these challenges and the mechanisms that
      mycobacteria employ to meet them. Because these organisms are difficult to study,
      in many cases we extrapolate from information known for gram-negative bacteria or
      more closely related GC-rich gram-positive organisms.

PMID- 18322041
TI  - Cilostazol improves long-term patency after percutaneous transluminal angioplasty
      in hemodialysis patients with peripheral artery disease.
AB  - BACKGROUND AND OBJECTIVES: Peripheral artery disease (PAD) is common in patients
      on hemodialysis (HD). Recently, cilostazol has been reported to reduce target
      lesion revascularization (TLR) after percutaneous transluminal angioplasty (PTA)
      for PAD in the general population. This study aimed to clarify the effects of
      cilostazol administration on long-term patency after PTA in HD patients. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: Three-hundred seventy-two consecutive
      lesions in 193 HD patients successfully undergoing PTA were enrolled in the study
      and divided into two groups: patients receiving 100 mg cilostazol twice daily in
      conjunction with standard therapy (130 lesions in 71 patients) and those not
      administered cilostazol (242 lesions in 122 patients). Effects of cilostazol on
      preventing restenosis after PTA in these patients were investigated. RESULTS:
      Kaplan-Meier analysis demonstrated the 5-yr patency rate was significantly higher
      in the cilostazol group than in the control group [52.4 versus 32.9%, hazard
      ratio (HR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, P = 0.0005]. Cox
      multivariate analysis revealed that administration of cilostazol was an
      independent predictor of preventing restenosis (HR 0.56, 95% CI 0.36 to 0.87, P =
      0.010). In 102 lesions matched after propensity score analysis, cilostazol had a
      beneficial effect on preventing restenosis (58.4 versus 34.7%, HR 0.47, 95% CI
      0.30 to 0.75, P = 0.0017) and was an independent predictor of preventing
      restenosis (HR 0.50; 95% CI 0.26 to 0.87, P = 0.014) after multivariate Cox
      analysis. CONCLUSIONS: Cilostazol administration improves long-term patency after
      PTA in HD patients with PAD.

PMID- 18322042
TI  - Prevalence of cysts in seminal tract and abnormal semen parameters in patients
      with autosomal dominant polycystic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease is a
      systemic disorder with a wide range of extrarenal involvement. The scope of this
      study was to analyze the prevalence of seminal cysts and to correlate these
      findings with the sperm parameters in patients with autosomal dominant polycystic
      kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective
      study enrolled 30 adult men with autosomal dominant polycystic kidney disease. Of
      these 30 patients, 22 agreed to provide a semen sample for analysis, and 28 of 30
      agreed to undergo an ultrasound rectal examination. Data obtained from the semen
      tests and from the ultrasound study were compared. RESULTS: Cysts in the seminal
      tract were present in 10 (43.47%) of 28 individuals. Twenty of 22 patients showed
      abnormal semen parameters, with asthenozoospermia as the most common finding. No
      correlation between ultrasound findings and sperm abnormalities was observed.
      CONCLUSIONS: The presence of cysts in the seminal tract is remarkably high
      (43.47%); however, this finding does not correlate with sperm abnormalities,
      which are also a frequent finding, especially asthenozoospermia. This semen
      abnormality is probably related to the abnormal function of polycystins. More
      attention should be paid to reproductive aspects in the initial evaluation of
      patients with autosomal dominant polycystic kidney disease before their ability
      to conceive is further impaired by uremia.

PMID- 18322044
TI  - Timing of initiation and discontinuation of renal replacement therapy in AKI:
      unanswered key questions.
AB  - Patients with acute kidney injury (AKI) often require initiation of renal
      replacement therapy (RRT). Currently, there is wide variation worldwide on the
      indications for and timing of initiation and discontinuation of RRT for AKI.
      Various parameters for metabolic, solute, and fluid control are generally used to
      guide the initiation and discontinuation of therapy; however, there are currently
      no standards in this field. Members of the recently established Acute Kidney
      Injury Network, representing key societies in critical care and nephrology along
      with additional experts in adult and pediatric AKI, participated in a 3-d
      conference in Vancouver in September 2006 to evaluate the available literature on
      this topic and draft consensus recommendations for research studies in this area.
      Key questions included the following: what are the indications for RRT, when
      should acute RRT support be initiated, and when should RRT be stopped? This
      report summarizes the available evidence and describes in detail the key
      questions, and some of the methods of answering them that will need to be
      addressed with the goal of standardizing the care of patients with AKI and
      improving outcomes.

PMID- 18322043
TI  - Unmasking glucose metabolism alterations in stable renal transplant recipients: a
      multicenter study.
AB  - BACKGROUND AND OBJECTIVES: Emerging information indicates that glucose metabolism
      alterations are common after renal transplantation and are associated with
      carotid atheromatosis. The aims of this study were to investigate the prevalence
      of different glucose metabolism alterations in stable recipients as well as the
      factors related to the condition. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      A multicenter, cross-sectional study was conducted of 374 renal transplant
      recipients without pre- or posttransplantation diabetes. A standard 75-g oral
      glucose tolerance test was performed. RESULTS: Glucose metabolism alterations
      were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose
      tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most
      common disorder was impaired glucose tolerance (17.9%), and an abnormal oral
      glucose tolerance test was observed for 21.5% of recipients with a normal fasting
      glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high
      density lipoprotein cholesterol ratio, and beta blocker use were shown to be
      factors related to glucose metabolism alterations. Remarkably, triglyceride
      levels, triglyceride/high-density lipoprotein cholesterol ratio, and the
      proportion of recipients with impaired fasting glucose were already higher
      throughout the first posttransplantation year in recipients with a current
      glucose metabolism alteration as compared with those without the condition.
      CONCLUSIONS: Glucose metabolism alterations are common in stable renal transplant
      recipients, and an oral glucose tolerance test is required for its detection.
      They are associated with a worse metabolic profile, which is already present
      during the first posttransplantation year. These findings may help planning
      strategies for early detection and intervention.

PMID- 18322038
TI  - Human RNA "rumor" viruses: the search for novel human retroviruses in chronic
      disease.
AB  - Retroviruses are an important group of pathogens that cause a variety of diseases
      in humans and animals. Four human retroviruses are currently known, including
      human immunodeficiency virus type 1, which causes AIDS, and human T-lymphotropic
      virus type 1, which causes cancer and inflammatory disease. For many years, there
      have been sporadic reports of additional human retroviral infections,
      particularly in cancer and other chronic diseases. Unfortunately, many of these
      putative viruses remain unproven and controversial, and some retrovirologists
      have dismissed them as merely "human rumor viruses." Work in this field was last
      reviewed in depth in 1984, and since then, the molecular techniques available for
      identifying and characterizing retroviruses have improved enormously in
      sensitivity. The advent of PCR in particular has dramatically enhanced our
      ability to detect novel viral sequences in human tissues. However, DNA
      amplification techniques have also increased the potential for false-positive
      detection due to contamination. In addition, the presence of many families of
      human endogenous retroviruses (HERVs) within our DNA can obstruct attempts to
      identify and validate novel human retroviruses. Here, we aim to bring together
      the data on "novel" retroviral infections in humans by critically examining the
      evidence for those putative viruses that have been linked with disease and the
      likelihood that they represent genuine human infections. We provide a background
      to the field and a discussion of potential confounding factors along with some
      technical guidelines. In addition, some of the difficulties associated with
      obtaining formal proof of causation for common or ubiquitous agents such as HERVs
      are discussed.

PMID- 18322045
TI  - Acute kidney injury: toward an integrated understanding through development of a
      research agenda.

PMID- 18322047
TI  - Multidrug-resistant gram-negative bacteria among patients who require chronic
      hemodialysis.
AB  - BACKGROUND AND OBJECTIVES: Multidrug-resistant gram-negative bacteria are rapidly
      spreading throughout the world. The epidemiology of multidrug-resistant gram
      negative bacteria in patients who require chronic hemodialysis has not been
      previously studied. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A prospective
      cohort study of an outpatient hemodialysis unit was conducted. Serial
      surveillance cultures for multidrug-resistant gram-negative bacteria, vancomycin
      resistant enterococci, and methicillin-resistant Staphylococcus aureus were
      collected from patients who were undergoing chronic hemodialysis. RESULTS:
      Nineteen (28%) of the 67 enrolled patients were colonized with one or more
      antimicrobial-resistant bacteria at study enrollment. Eleven (16%), nine (13%),
      and three (5%) patients were colonized with multidrug-resistant gram-negative
      bacteria, vancomycin-resistant enterococci, and methicillin-resistant
      Staphylococcus aureus, respectively. Independent risk factors associated with
      harboring multidrug-resistant gram-negative bacteria at enrollment were residence
      in a long-term care facility and antibiotic exposure for > or = 7 d in the
      previous 3 mo. Twenty-two (40%) of 55 patients who had follow-up cultures
      acquired at least one antimicrobial-resistant bacterium. A total of 20, 15, and
      13% of patients acquired multidrug-resistant gram-negative bacteria, vancomycin
      resistant enterococci, and methicillin-resistant Staphylococcus aureus,
      respectively. Antibiotic exposure was the only independent risk factor for
      multidrug-resistant gram-negative bacteria acquisition. Endogenous multidrug
      resistant gram-negative bacteria acquisition was detected among 69% of acquired
      multidrug-resistant gram-negative bacterial strains. CONCLUSIONS: The prevalence
      and acquisition of multidrug-resistant gram-negative bacteria surpassed that of
      vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus.
      Endogenous acquisition, as opposed to patient-to-patient spread, was the
      predominant mechanism of acquisition. Residence in a long-term care facility and
      antibiotic exposure may be important factors promoting the spread of multidrug
      resistant gram-negative bacteria among this patient population.

PMID- 18322046
TI  - Impact of acute rejection and new-onset diabetes on long-term transplant graft
      and patient survival.
AB  - BACKGROUND AND OBJECTIVES: Development of new therapeutic strategies to improve
      long-term transplant outcomes requires improved understanding of the mechanisms
      by which these complications limit long-term transplant survival. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: The association of acute rejection and new
      onset diabetes was determined in the first posttransplantation year with the
      outcomes of transplant failure from any cause, death-censored graft loss, and
      death with a functioning graft in 27,707 adult recipients of first kidney-only
      transplants, with graft survival of at least 1 yr, performed between 1995 and
      2002 in the United States. RESULTS: In multivariate analyses, patients who
      developed acute rejection or new-onset diabetes had a similar risk for transplant
      failure from any cause, but the mechanisms of transplant failure were different:
      Acute rejection was associated with death-censored graft loss but only weakly
      associated with death with a functioning graft. In contrast new-onset diabetes
      was not associated with death-censored graft loss but was associated with an
      increased risk for death with a functioning graft. CONCLUSIONS: Acute rejection
      and new-onset diabetes have a similar impact on long-term transplant survival but
      lead to transplant failure through different mechanisms. The mechanisms by which
      new-onset diabetes leads to transplant failure should be prospectively studied.
      Targeted therapeutic strategies to minimize the impact of various early
      posttransplantation complications may lead to improved long-term outcomes.

PMID- 18322048
TI  - Does vitamin D receptor and calcium receptor activation therapy play a role in
      the histopathologic alterations of parathyroid glands in refractory uremic
      hyperparathyroidism?
AB  - BACKGROUND AND OBJECTIVES: Vitamin D receptor activation by vitamin D sterols and
      calcium-sensing receptor stimulation by cinacalcet are the most powerful
      treatments of secondary hyperparathyroidism. This study was aimed to assess a
      possible association between histopathologic changes of parathyroid tissue and
      treatment modality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Studies were
      performed on 82 parathyroids of 22 adult white hemodialysis patients undergoing
      first parathyroidectomy. The type of hyperplasia and the distribution of chief
      and oxyphil cells, expressed as oxyphil/chief cell ratio, were assessed. Three
      groups could be studied according to treatment modality: group A consisted of 6
      patients who were treated with cinacalcet, intravenous calcitriol, and phosphate
      binders; group B consisted of 6 patients who were treated with intravenous
      calcitriol and phosphate binders, and group C consisted of 10 patients who were
      treated with phosphate binders alone. RESULTS: Sixty-eight (82.9%) out of 82
      glands removed showed nodular hyperplasia. It was more frequent in groups A and B
      than in group C. A stepwise forward logistic regression model showed that the
      probability of nodular hyperplasia was higher in patients who were on calcitriol
      and/or cinacalcet therapy, in female gender and in patients with a higher body
      mass index. Oxyphil/chief cell ratio also was significantly different among the
      three groups. Cinacalcet treatment was the only predictor of this ratio.
      CONCLUSIONS: An association was found between calcitriol and/or cinacalcet
      therapy and a high prevalence of nodular hyperplasia, and between cinacalcet
      therapy and high oxyphil/chief cell ratio. The meaning of the observed
      associations remains uncertain.

PMID- 18322049
TI  - New challenges and paradigms for mid-career faculty in academic medical centers:
      key strategies for success for mid-career medical school faculty.

PMID- 18322050
TI  - Contribution of bone and mineral abnormalities to cardiovascular disease in
      patients with chronic kidney disease.
AB  - 1,25-Dihydroxyvitamin D(3) levels begin to drop early in the course of kidney
      disease, leading to elevated parathyroid hormone levels and disrupted mineral
      metabolism. Impaired mineral metabolism seems to be associated not only with bone
      disease but also with vascular calcification. Animal models have identified
      molecular mechanisms by which high mineral levels and other uremic substances
      induce vascular smooth muscle cells to undergo phenotypic changes that initiate
      the calcification process. Moreover, several epidemiologic and clinical studies
      showed strong associations between bone loss, arterial calcification, and
      cardiovascular disease in populations with and without kidney disease. This
      review discusses evidence that two early complications of chronic kidney disease-
      vitamin D deficiency and secondary hyperparathyroidism--contribute to bone and
      cardiovascular disease. New treatment strategies aimed at the prevention of bone
      loss and parathyroid hyperplasia, such as vitamin D receptor ligand therapy,
      calcimimetic agents, and noncalcifying phosphate binders, are being investigated
      for their impact on improving overall outcome in dialysis patients.

PMID- 18322052
TI  - Introduction: new insights, treatments, and management strategies for ADPKD.

PMID- 18322051
TI  - Relation of low glomerular filtration rate to metabolic disorders in individuals
      without diabetes and with normoalbuminuria.
AB  - BACKGROUND AND OBJECTIVES: Microalbuminuria increases cardiovascular risk and is
      considered a metabolic disorder. Low glomerular filtration rate is also
      associated with increased cardiovascular risk, but the relation of low glomerular
      filtration rate to metabolic disorders is not well understood. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: Designed as a cross-sectional, epidemiologic study,
      the Insulin Resistance Atherosclerosis Study was conducted in four centers: San
      Antonio (Texas), San Luis Valley (Colorado), and Oakland and Los Angeles
      (California). The Modification of Diet in Renal Disease equation was used to
      classify individuals without diabetes and with normoalbuminuria (n = 856; age 40
      to 69 yr) by the presence or absence of low glomerular filtration rate (<60
      ml/min per 1.73 m(2)). A direct marker of insulin resistance, the insulin
      sensitivity index, was measured by the frequently sampled intravenous glucose
      tolerance test. RESULTS: Low glomerular filtration rate was related to
      hypertension and the metabolic syndrome. Low glomerular filtration rate was
      associated with fasting insulin concentration and insulin sensitivity index. Low
      glomerular filtration rate was also associated with insulin concentration after
      adjustment for potential determinants of glomerular filtration rate but was not
      associated with insulin sensitivity index. CONCLUSIONS: Low glomerular filtration
      rate is associated with increased insulin concentration in individuals without
      diabetes and with normoalbuminuria. Longitudinal analyses are needed to determine
      whether insulin concentration (insulin resistance) precedes the deterioration of
      renal function.

PMID- 18322053
TI  - Cardiovascular outcomes in the outpatient kidney transplant clinic: the
      Framingham risk score revisited.
AB  - BACKGROUND AND OBJECTIVES: Cardiovascular disease is an important cause of
      morbidity and death in kidney transplant recipients. This study examines the
      Framingham risk score's ability to predict cardiac and stroke events. Because
      cyclosporine and tacrolimus have different cardiovascular risk profiles, these
      agents were also examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A
      prospective cohort evaluation of 540 patients were followed for a median of 4.7
      yr in an outpatient kidney transplant clinic. Baseline Framingham risk scores
      were calculated and all cardiovascular outcomes were collected. RESULTS: Rates
      per 100 patient-years were 1.79 for cardiac and 0.78 for stroke events. The ratio
      of observed-to-predicted cardiac events was 1.64-fold higher [95% confidence
      interval (CI) 1.19 to 2.94] for the cohort, 2.74-fold higher (95% CI 1.70 to
      4.24) in patients age 45 to 60 with prior cardiac disease or diabetes mellitus,
      but not higher in other age subgroups. Stroke was not increased above predicted.
      Risk scores for cardiac (c = 0.65, P = 0.003) and stroke (c = 0.71, P = 0.004)
      events were modest predictors. 10-yr event scores for cardiac (9.3 versus 13.5%,
      P < 0.001) and stroke (7.1 versus 10.0%, P = 0.002) were lower for tacrolimus
      compared with cyclosporine-treated patients. However observed cardiac events were
      higher in tacrolimus recipients (2.50, 95% CI 1.09 to 5.90) in an adjusted Cox
      model. CONCLUSIONS: Although risk scores are only modest predictors, patients
      with the highest event rates are easily identified. Treating high-risk patients
      with cardioprotective medications should remain a priority.

PMID- 18322054
TI  - Emergence of a tetracycline-resistant Campylobacter jejuni clone associated with
      outbreaks of ovine abortion in the United States.
AB  - Campylobacter infection is one of the major causes of ovine abortions worldwide.
      Historically, Campylobacter fetus subsp. fetus was the major cause of
      Campylobacter-associated abortion in sheep; however, Campylobacter jejuni is
      increasingly associated with sheep abortions. We examined the species
      distribution, genotypes, and antimicrobial susceptibilities of abortion
      associated Campylobacter isolates obtained from multiple lambing seasons on
      different farms in Iowa, Idaho, South Dakota, and California. We found that C.
      jejuni has replaced C. fetus as the predominant Campylobacter species causing
      sheep abortion in the United States. Most strikingly, the vast majority (66 of
      71) of the C. jejuni isolates associated with sheep abortion belong to a single
      genetic clone, as determined by pulsed-field gel electrophoresis, multilocus
      sequence typing, and cmp gene (encoding the major outer membrane protein)
      sequence typing. The in vitro antimicrobial susceptibilities of these isolates to
      the antibiotics that are routinely used in food animal production were determined
      using the agar dilution test. All of the 74 isolates were susceptible to
      tilmicosin, florfenicol, tulathromycin, and enrofloxacin, and 97% were sensitive
      to tylosin. However, all were resistant to tetracyclines, the only antibiotics
      currently approved in the United States for the treatment of Campylobacter
      abortion in sheep. This finding suggests that feeding tetracycline for the
      prevention of Campylobacter abortions is ineffective and that other antibiotics
      should be used for the treatment of sheep abortions in the United States.
      Together, these results indicate that a single tetracycline-resistant C. jejuni
      clone has emerged as the major cause of Campylobacter-associated sheep abortion
      in the United States.

PMID- 18322055
TI  - Metallo-beta-lactamase detection: comparative evaluation of double-disk synergy
      versus combined disk tests for IMP-, GIM-, SIM-, SPM-, or VIM-producing isolates.
AB  - The emergence of metallo-beta-lactamase (MBL)-producing isolates is a challenge
      to routine microbiology laboratories, since there are no standardized methods for
      detecting such isolates. The aim of this study was to evaluate the accuracy of
      different phenotypic methods to detect MBL production among Pseudomonas spp.,
      Acinetobacter spp., and enterobacterial isolates, including GIM, IMP, SIM, SPM,
      and VIM variants. A total of 46 genetically unrelated Pseudomonas aeruginosa,
      Pseudomonas putida, Acinetobacter sp., and enterobacterial strains producing
      distinct MBLs were tested. Nineteen strains were included as negative controls.
      The inhibition of bacterial growth and beta-lactam hydrolysis caused by MBL
      inhibitors (IMBL) also were evaluated. The isolates were tested for MBL
      production by both a double-disk synergy test (DDST) and a combined disk assay
      (CD) using imipenem and ceftazidime as substrates in combination with distinct
      IMBL. One hundred percent sensitivity and specificity were achieved by DDST using
      2-mercaptopropionic acid in combination with ceftazidime and imipenem for the
      detection of MBL production among P. aeruginosa and Acinetobacter species
      isolates, respectively. The CD test showed the same results for detecting MBL
      producing enterobacteria by combining imipenem and EDTA, with a 5.0-mm-breakpoint
      increase in the size of the inhibition zone. Our results indicate that both
      phenotypic methods to detect MBL-producing isolates should be based on the genera
      to be tested, regardless of the enzyme produced by such isolates, as well as on
      the local prevalence of MBL producers.

PMID- 18322056
TI  - Immunoglobulin G responses to a panel of Candida albicans antigens as accurate
      and early markers for the presence of systemic candidiasis.
AB  - Despite shortcomings, cultures of blood and sterile sites remain the "gold
      standard" for diagnosing systemic candidiasis. Alternative diagnostic markers,
      including antibody detection, have been developed, but none are widely accepted.
      In this study, we used an enzyme-linked immunosorbent assay to measure serum
      antibody responses against 15 recombinant Candida albicans antigens among 60
      patients with systemic candidiasis due to various Candida spp. and 24 uninfected
      controls. Mean immunoglobulin G (IgG) responses against all 15 antigens were
      significantly higher among patients with systemic candidiasis than among
      controls, whereas IgM responses were higher against only seven antigens. Using
      discriminant analysis that included IgG responses against the 15 antigens, we
      derived a mathematical prediction model that identified patients with systemic
      candidiasis with an error rate of 3.7%, a sensitivity of 96.6%, and a specificity
      of 95.6%. Furthermore, a prediction model using a subset of four antigens (SET1,
      ENO1, PGK1-2, and MUC1-2) identified through backward elimination and canonical
      correlation analyses performed as accurately as the full panel. Using the
      simplified model, we predicted systemic candidiasis in a separate test sample of
      32 patients and controls with 100% sensitivity and 87.5% specificity. We also
      demonstrated that IgG titers against each of the four antigens included in the
      prediction model were significantly higher in convalescent-phase sera than in
      paired acute-phase sera. Taken together, our findings suggest that IgG responses
      against a panel of candidal antigens might represent an accurate and early marker
      of systemic candidiasis, a hypothesis that should be tested in future trials.

PMID- 18322057
TI  - Evaluation of the new Micronaut-Candida system compared to the API ID32C method
      for yeast identification.
AB  - A new system, Micronaut-Candida, was compared to API ID32C to identify 264 yeast
      (Candida albicans, C. parapsilosis, C. tropicalis, C. krusei, C. inconspicua, C.
      norvegensis, C. lusitaniae, C. guilliermondii, C. dubliniensis, C. pulcherrima,
      C. famata, C. rugosa, C. glabrata, C. kefyr, C. lipolytica, C. catenulata, C.
      neoformans, Geotrichum and Trichosporon species, Rhodotorula glutinis, and
      Saccharomyces cerevisiae) clinical isolates. Results were in concordance in 244
      cases. Eighteen out of the 20 of discordant results were correctly identified by
      Micronaut-Candida but not by API ID32C, as confirmed by PCR ribotyping.

PMID- 18322058
TI  - Clinical characteristics associated with isolation of small-colony variants of
      Staphylococcus aureus and Pseudomonas aeruginosa from respiratory secretions of
      patients with cystic fibrosis.
AB  - During a 3-month period, small-colony variant phenotypes of both Staphylococcus
      aureus and Pseudomonas aeruginosa were isolated from respiratory secretions of
      8.2% and 9.2%, respectively, of 98 patients with cystic fibrosis, particularly
      those with advanced pulmonary disease and prolonged antibiotic exposure.

PMID- 18322059
TI  - Detection of diarrheagenic Escherichia coli by use of melting-curve analysis and
      real-time multiplex PCR.
AB  - Diarrheagenic Escherichia coli strains are important causes of diarrhea in
      children from the developing world and are now being recognized as emerging
      enteropathogens in the developed world. Current methods of detection are too
      expensive and labor-intensive for routine detection of these organisms to be
      practical. We developed a real-time fluorescence-based multiplex PCR for the
      detection of all six of the currently recognized classes of diarrheagenic E.
      coli. The primers were designed to specifically amplify eight different virulence
      genes in the same reaction: aggR for enteroaggregative E. coli, stIa/stIb and lt
      for enterotoxigenic E. coli, eaeA for enteropathogenic E. coli and Shiga toxin
      producing E. coli (STEC), stx(1) and stx(2) for STEC, ipaH for enteroinvasive E.
      coli, and daaD for diffusely adherent E. coli (DAEC). Eighty-nine of ninety
      diarrheagenic E. coli and 36/36 nonpathogenic E. coli strains were correctly
      identified using this approach (specificity, 1.00; sensitivity, 0.99). The single
      false negative was a DAEC strain. The total time between preparation of DNA from
      E. coli colonies on agar plates and completion of PCR and melting-curve analysis
      was less than 90 min. The cost of materials was low. Melting-point analysis of
      real-time multiplex PCR is a rapid, sensitive, specific, and inexpensive method
      for detection of diarrheagenic E. coli.

PMID- 18322060
TI  - Agammaglobulinemia and Staphylococcus aureus botryomycosis in a cohort of related
      sentinel Swiss Webster mice.
AB  - Sentinel mouse seroconversion to infectious agents is critical for laboratory
      animal facility disease monitoring. We report spontaneous emergence of non-sex
      linked agammaglobulinemia with B-cell deficiency and cutaneous Staphylococcus
      aureus granulomatosis (botryomycosis) in a cohort of related Swiss Webster
      sentinel mice. Our experience reinforces the importance of immunocompetency
      validation in surveillance programs.

PMID- 18322061
TI  - Alternative algorithms for human immunodeficiency virus infection diagnosis using
      tests that are licensed in the United States.
AB  - Serodiagnosis of human immunodeficiency virus (HIV) infection in the United
      States has traditionally relied on a sequential two-test algorithm: an initial
      screen with an enzyme immunoassay (EIA) and reflex testing of EIA-reactive
      specimens with a more specific supplemental test such as Western blotting or
      immunofluorescence. The supplemental tests are tedious, subjective, and
      expensive. In addition, there have been major improvements in the performance and
      accuracy of the EIA tests as well as the introduction of rapid serologic tests
      (RT) and HIV nucleic acid amplification tests (NAAT). Related to these
      improvements is the possibility that alternative algorithms using combinations of
      currently approved HIV tests may function as well as if not better than the
      current algorithm, with more flexibility, improved accuracy, and lower cost. To
      this end, we evaluated the performance of 12 currently licensed tests and 1 in
      house HIV test (6 EIA, 4 RT, and 3 NAAT) on panels of plasma samples from HIV
      infected (n = 621 HIV type 1 [HIV-1] and 34 HIV-2) and uninfected (n = 513)
      people and of sequential specimens from people early in seroconversion (183
      specimens from 15 patients). Test combinations were analyzed in two dual-test
      (sensitivity-optimized and specificity-optimized) algorithms and in a three-test
      (tie-breaking) algorithm, and performance was compared to the conventional
      algorithm. The results indicate that alternative algorithm strategies with
      currently licensed tests compare favorably with the conventional algorithm in
      detecting and confirming established HIV infection. Furthermore, there was a
      lower frequency of discordant or indeterminate results that require follow-up
      testing, and there was improved detection of early infection.

PMID- 18322062
TI  - Evaluation of CDC-recommended approaches for confirmatory testing of positive
      Neisseria gonorrhoeae nucleic acid amplification test results.
AB  - We evaluated three of the CDC approaches for confirming Neisseria gonorrhoeae
      (gonococcus [GC])-positive nucleic acid amplification test (NAAT) results: (i)
      repeating the original test on the original specimen, (ii) testing the original
      specimen with a different test, and (iii) performing a different test on a
      duplicate specimen collected at the same visit. For the first approach, clinical
      specimens were initially tested by Aptima Combo 2 (AC2) (Gen-Probe Inc., San
      Diego, CA), ProbeTec (strand displacement amplification [SDA]) (Becton Dickinson
      Co., Sparks, MD), and Amplicor (PCR) (Roche Molecular Systems, Branchburg, NJ).
      The original GC-positive specimens were then retested by the same NAAT for
      confirmation. For the second approach, specimens initially positive by AC2, SDA,
      or PCR were retested by different NAATs (SDA, PCR, AC2, and Aptima Neisseria
      gonorrhoeae assay [AGC]; Gen-Probe Inc.). For the third approach, duplicate
      urethral swabs and first-catch urine (FCU) samples from men and duplicate
      cervical swabs and FCU samples from women were each tested by SDA, AC2, and AGC
      in parallel. We found that 89 to 96% of samples positive by SDA, PCR, and AC2
      were confirmed by repeat testing and that 85 to 98% of SDA, PCR, and AC2 results
      were confirmed by using different NAATs on the original specimen. For FCU samples
      from men, any NAAT can be used for confirmation. However, for all other specimen
      types, some NAATs cannot be used to confirm positive results from other NAATs.
      Thus, a single repeat test appears to be a reliable method for confirmation, but
      by doing more extensive testing, an additional 5% were confirmed. With >90% of
      all GC-positive NAATs being confirmed, our results show that confirmatory testing
      is not warranted for these genital specimens.

PMID- 18322063
TI  - Pilot study of prevalence of high-risk human papillomavirus genotypes in Israeli
      Jewish women referred for colposcopic examination.
AB  - The objective of the present study was to determine the prevalence of high-risk
      (HR) human papillomavirus (HPV) genotypes in a group of Israeli Jewish women
      referred for colposcopic examination. Scrape specimens were prospectively
      collected from 84 women referred for colposcopic examination. All the women
      underwent Papanicolaou (Pap) smears and colposcopies, and some also underwent
      cervical or loop electrosurgical excision procedure biopsy. HR HPV was detected
      in scrape specimens (Amplicor HPV test; Roche Molecular Systems), and the
      individual genotypes in these specimens were identified (HPV GenoArray test kit;
      Hybribio Ltd., Hong Kong). Forty-one (49%) specimens were positive by the
      Amplicor HPV test. Sixty-four samples (41 positive and 23 negative by the
      Amplicor HPV test) were also assayed by use of the HPV GenoArray kit. The overall
      level of agreement between the two assays was 93.8% (Cohen's kappa = 0.98). HR
      genotypes were found in 37/41 (90%) HPV-positive samples. The prevalences of the
      HR HPV genotypes in the 37 HPV-positive samples were 41% of patients for HPV type
      16 (HPV-16), 22% for HPV-39, 19% for HPV-52, and 14% for HPV-18. Forty-one
      percent of these patients were infected with a single HR genotype, whereas 59%
      were infected with mixtures of HR genotypes. The presence of a relatively high
      percentage of HPV types 39 and 52 and the relatively high incidence of infections
      with mixtures of genotypes may be one of the reasons for the low rate of
      conversion from high-grade squamous intraepithelial lesions to invasive carcinoma
      in Israeli women. Larger and more comprehensive studies are warranted to
      investigate this issue in greater detail.

PMID- 18322064
TI  - Evaluation of different techniques for identification of human papillomavirus
      types of low prevalence.
AB  - Human papillomaviruses (HPVs) have been recognized as etiologic factors in a
      variety of diseases. Due to the large number of HPV types, methods for HPV
      genotyping are difficult to standardize. Despite this fact, several methods
      exist, and some of them are available commercially. In this study, we evaluated
      the Roche Diagnostics linear array (LA) HPV genotyping assay, the Innogenetics
      INNO-LiPA (line probe assay [LiPA]), and two noncommercial reverse line blot
      (RLB) assays based on either primers GP5+ and GP6+ (GP) or newly designed broad
      spectrum primers BSGP5+ and BSGP6+ (BS). The reliabilities of these assays were
      tested with a wide spectrum of HPV types less prevalent in cervical samples. This
      is the first study to compare the performance of the most widely used HPV
      genotyping methods with selected samples positive for low-prevalence HPV types.
      We focused on interassay agreement, both overall and type specific, in cases with
      single and/or multiple HPV infections. Interassay agreement was moderate in cases
      of single HPV infections and poor in cases of multiple HPV infections. The LA and
      the BS-based RLB assays found a higher rate of cases positive for multiple HPV
      types than LiPA and the GP-based RLB assay. The weakest capability in detecting
      multiple HPV infections was observed for LiPA. The use of only one assay in
      epidemiological and clinical studies might lead to biased conclusions. Therefore,
      a universally evaluated and agreed upon HPV typing assay or a combination of
      current assays is needed for possible clinical applications, and knowledge of
      their limitations is advised.

PMID- 18322065
TI  - Current trends in rapid diagnostics for methicillin-resistant Staphylococcus
      aureus and glycopeptide-resistant enterococcus species.

PMID- 18322066
TI  - Evaluation of the NanoChip 400 system for detection of influenza A and B,
      respiratory syncytial, and parainfluenza viruses.
AB  - The NanoChip400 system uses multiplex PCR chemistry and electronic microarray
      detection of influenza A and B viruses; respiratory syncytial viruses A and B;
      and human parainfluenza virus types 1, 2, and 3. The results obtained with the
      NanoChip 400 system were compared with those obtained by direct fluorescent
      antibody staining (DFA) and real-time PCR with 122 and 130 specimens,
      respectively. Concordance between DFA and NanoChip 400 system was obtained for
      106 of 122 (86.9%) specimens. On the basis of discrepancy analysis with specimens
      available for confirmatory real-time PCR testing, the sensitivity and specificity
      of the NanoChip 400 were 98.6% and 100%, respectively. With respect to specimens
      previously tested by real-time PCR, the NanoChip 400 system demonstrated a
      sensitivity of 91.1% and a specificity of 100%. The NanoChip 400 system provides
      clinical laboratories with a practical, rapid, and sensitive method for the
      detection of common respiratory viruses.

PMID- 18322067
TI  - Genotypic diversity of anaerobic isolates from bloodstream infections.
AB  - Accurate species determination for anaerobes from blood culture bottles has
      become increasingly important with the reemergence of anaerobic bacteremia and
      prevalence of multiple-drug-resistant microorganisms. Our knowledge of the
      taxonomical diversity of anaerobes that cause bloodstream infections is extremely
      limited, because identification historically has relied on conventional methods.
      Over a 5-year period, we profiled anaerobic bacteremia at a large tertiary care
      hospital with 16S rRNA gene sequencing to gain a better understanding of the
      taxonomical diversity of the bacteria. Of 316 isolates, 16S rRNA gene sequencing
      and phylogenetic analysis identified 316 (100%) to the genus or taxonomical group
      level and 289 (91%) to the species level. Conventional methods identified 279
      (88%) to the genus level and 208 (66%) to the species level; 75 (24%) were
      misidentified at the species level, and 33 (10%) results were inconclusive. High
      intragenus variability was observed for Bacteroides and Clostridium species, and
      high intraspecies variability was observed for Bacteroides thetaiotaomicron and
      Fusobacterium nucleatum. Sequence-based identification has potential benefits in
      comparison to conventional methods, because it more accurately characterizes
      anaerobes within taxonomically related clusters and thereby may enable better
      correlation with specific clinical syndromes and antibiotic resistance patterns.

PMID- 18322068
TI  - Emergence and dissemination of a community-associated methicillin-resistant
      Panton-Valentine leucocidin-positive Staphylococcus aureus clone sharing the
      sequence type 5 lineage with the most prevalent nosocomial clone in the same
      region of Argentina.
AB  - Epidemiological surveillance for community-associated methicillin-resistant
      Staphylococcus aureus revealed prevalences of 33% and 13% in pediatric and adult
      patients, respectively, in Cordoba, Argentina, in 2005. This study describes for
      the first time the emergence and dissemination of the sequence type 5 (ST5)
      lineage as the most prevalent clone (89%) (pulsed-field gel electrophoresis type
      I-ST5-staphylococcal cassette chromosome type IVa-spa type 311) harboring the
      Panton-Valentine leukocidin and enterotoxin A genes.

PMID- 18322070
TI  - Inability of real-time reverse transcriptase PCR assay to detect subtype H7 avian
      influenza viruses isolated from wild birds.
AB  - We report a failure of the real-time reverse transcriptase PCR H7 subtyping
      protocol currently used in national avian influenza surveillance programs.
      Significant substitutions in primer and probe target sequences were identified,
      especially in wild bird viruses. The protocol, originally designed for detecting
      H7 influenza viruses in poultry, is not reliable for wild bird surveillance.

PMID- 18322069
TI  - High-throughput genotyping of Salmonella enterica serovar Typhi allowing
      geographical assignment of haplotypes and pathotypes within an urban District of
      Jakarta, Indonesia.
AB  - High-throughput epidemiological typing systems that provide phylogenetic and
      genotypic information are beneficial for tracking bacterial pathogens in the
      field. The incidence of Salmonella enterica serovar Typhi infection in Indonesia
      is high and is associated with atypical phenotypic traits such as expression of
      the j and the z66 flagellum antigens. Utilizing a high-throughput genotyping
      platform to investigate known nucleotide polymorphisms dispersed around the
      genome, we determined the haplotypes of 140 serovar Typhi isolates associated
      with Indonesia. We identified nine distinct serovar Typhi haplotypes circulating
      in Indonesia for more than 30 years, with eight of these present in a single
      Jakarta suburb within a 2-year period. One dominant haplotype, H59, is associated
      with j and z66 flagellum expression, representing a potential pathotype unique to
      Indonesia. Phylogenetic analysis suggests that H59 z66(+), j(+) isolates emerged
      relatively recently in terms of the origin of serovar Typhi and are
      geographically restricted. These data demonstrate the potential of high
      throughput genotyping platforms for analyzing serovar Typhi populations in the
      field. The study also provides insight into the evolution of serovar Typhi and
      demonstrates the value of a molecular epidemiological technique that is
      exchangeable, that is internet friendly, and that has global utility.

PMID- 18322071
TI  - The development of drug metabolism research as expressed in the publications of
      ASPET: Part 2, 1959-1983.
AB  - In 25 years, drug metabolism research went from using subcellular particles of
      undefined content to an understanding of metabolism at the molecular level. The
      discoveries of cytochrome P450, enzyme induction, reactive intermediates, and
      genetic polymorphisms were milestones in the field. New publications from the
      American Society for Pharmacology and Experimental Therapeutics chronicled the
      discoveries and provided communications to advance the science of drug
      metabolism.

PMID- 18322072
TI  - Aldo-keto reductase 1C2 fails to metabolize doxorubicin and daunorubicin in
      vitro.
AB  - The anthracycline drugs are important for the treatment of a number of
      malignancies; however, their clinical use is associated with dose-dependent
      severe chronic cardiotoxicity. Although the mechanism for this side effect has
      not yet been identified, the alcohol metabolites formed during daunorubicin
      (DAUN) and doxorubicin (DOX) therapies have been implicated. The alcohol
      metabolites of DAUN and DOX, daunorubicinol (DAUNol) and doxorubicinol (DOXol),
      respectively, are generated through reduction of the C-13 carbonyl function,
      which is reportedly mediated by members of the aldo-keto reductase and carbonyl
      reductase families of proteins. In our search for potential biomarkers for the
      occurrence of this side effect, we examined the activity of recombinant aldo-keto
      reductase enzymes, aldo-keto reductase (AKR) 1A1 and AKR1C2, with DAUN and DOX as
      substrates. Using purified histidine-tagged recombinant proteins and the direct
      measurement of metabolite formation with a high-performance liquid chromatography
      fluorescence assay, we did not observe DAUNol or DOXol generation in vitro by
      AKR1C2, whereas AKR1A1 did catalyze the reduction reactions. DAUNol was generated
      by AKR1A1 at a rate of 1.71 +/- 0.09 nmol/min/mg protein, and a low level of
      DOXol was produced by AKR1A1; however, it was below the limits of quantification
      for the method. These data suggest that the generation of DAUNol or DOXol by
      AKR1C2 metabolism in vivo is unlikely to occur during anthracycline treatment.

PMID- 18322073
TI  - PDZK1 regulates two intestinal solute carriers (Slc15a1 and Slc22a5) in mice.
AB  - Gastrointestinal (GI) absorption of certain therapeutic agents is thought to be
      mediated by solute carrier (SLC) transporters, although minimal in vivo evidence
      has been reported. Here, we show key roles of postsynaptic density 95/disk
      large/ZO-1 (PDZ) domain-containing protein, PDZK1, as a regulatory mechanism of
      two solute carriers, Slc15a1 (oligopeptide transporter PEPT1) and Slc22a5
      (carnitine/organic cation transporter OCTN2) in mouse small intestine by using
      pdzk1 gene knockout (pdzk1(-/-)) mice. GI absorption of cephalexin, a substrate
      of PEPT1, after p.o. administration was delayed in pdzk1(-/-) mice compared with
      wild-type mice. Absorption of carnitine, a substrate of OCTN2, was also decreased
      in pdzk1(-/-) mice. Immunohistochemical analysis revealed the localization of
      both PEPT1 and OCTN2 at apical membrane of small intestinal epithelial cells in
      wild-type mice, whereas such apical localization was reduced in pdzk1(-/-) mice,
      with a concomitant decrease in their protein levels assessed by Western blotting
      in intestinal brush-border membranes. Electron microscopy revealed localization
      of PEPT1 in intracellular vesicular structures in pdzk1(-/-) mice. In addition,
      we first identified interaction between PEPT1 and PDZK1 in mouse small intestine
      and found that PDZK1 stimulates transport activity of PEPT1 by increasing its
      expression level in human embryonic kidney 293 cells. Taken together, the present
      findings provide direct evidence that PDZK1 regulates two intestinal SLC
      transporters in vivo as an adaptor protein for these transporters and affects
      oral absorption of their substrates. These findings also raise the possibility
      that intestinal absorption of the substrate drugs for PEPT1 and OCTN2 is governed
      by the protein network of these transporters and their adaptor PDZK1.

PMID- 18322074
TI  - Identification of human liver cytochrome P450 isoforms involved in autoinduced
      metabolism of the antiangiogenic agent (Z)-5-[(1,2-dihydro-2-oxo-3H-indol-3
      ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-propanoic acid (TSU-68).
AB  - (Z)-5-[(1,2-Dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3
      propanoic acid (TSU-68) is a new anticancer drug that inhibits angiogenic
      receptor tyrosine kinases, which play a crucial role in tumor-induced
      vascularization. TSU-68 undergoes hepatic oxidation and glucuronidation.
      Incubation of TSU-68 with human liver microsomes in the presence of NADPH
      resulted in the formation of three major metabolites: 5-, 6-, and 7
      hydroxyindolinone derivatives. The 5-, 6-, and 7-hydroxylation followed simple
      Michaelis-Menten kinetics with V(max)/K(m) values (an indicator of intrinsic
      clearance) of 13, 25, and 6 microl/min/mg, respectively. Of the 10 cDNA-expressed
      human cytochrome P450 isoforms examined, only CYP1A1 and CYP1A2 exhibited
      appreciable TSU-68 hydroxylation activity. Inhibition studies with alpha
      naphthoflavone (a selective CYP1A2 inhibitor) and anti-CYP1A2 antibody also
      indicated the almost exclusive role of CYP1A2 in microsomal TSU-68 hydroxylation.
      Treatment of human hepatocytes with 10 microM TSU-68 resulted in a 28- to 140
      fold increase in CYP1A1/2-mediated ethoxyresorufin O-deethylase activity. The
      protein levels of CYP1A2 were increased in TSU-68-treated hepatocytes, and those
      of CYP1A1, which were undetectable in control hepatocytes, were also increased to
      detectable levels in the TSU-68-treated hepatocytes. Thus, TSU-68 was shown to
      induce CYP1A1/2 expression, which was responsible for its hydroxylation. The
      observation that TSU-68 treatment resulted in a 10- to 45-fold increase in 5-, 6
      , and 7-hydroxylation directly demonstrated the autoinduced hydroxylation of TSU
      68. In conclusion, TSU-68 has the potential to cause induction of its own
      CYP1A1/2-mediated oxidative metabolism in humans. This autoinductive effect
      provides a clear explanation for the clinically observed decrease in TSU-68
      plasma concentrations during repeated administration of the drug.

PMID- 18322075
TI  - Quantitative investigation of the role of breast cancer resistance protein
      (Bcrp/Abcg2) in limiting brain and testis penetration of xenobiotic compounds.
AB  - The role of breast cancer resistance protein (BCRP/ABCG2) in limiting the brain
      and testis penetration of xenobiotic compounds in the blood-brain and -testis
      barriers was investigated using Bcrp(-/-) mice. Tissue/plasma concentration
      ratios in the brain (K(p,brain)) and testis (K(p,testis)) obtained under steady
      state conditions were significantly increased in Bcrp(-/-) mice for PhIP (2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine), N-hydroxyl PhIP, MeIQx (2-amino-3,8
      dimethylimidazo[4,5-f]quinoxaline), dantrolene, and prazosin. In addition, the
      K(p,brain) of triamterene and the K(p,testis) of 4'-hydroxyl PhIP were also
      significantly increased in Bcrp(-/-) mice. The effect of functional impairment of
      Bcrp on the brain uptake of PhIP, dantrolene, and daidzein in Bcrp(-/-) mice
      determined using in situ brain perfusion was weaker than that observed on the
      K(p) values. In vitro transcellular transport experiments using cell lines
      expressing mouse Bcrp or P-glycoprotein (Mdr1a/Abcb1a) showed that, among the
      tested Bcrp substrates, PhIP, MeIQx, prazosin, and triamterene are common
      substrates of Bcrp and P-glycoprotein. The K(p) values of common substrates
      exhibited a smaller increase both in the brain and testis of Bcrp(-/-) mice than
      expected from the in vitro Bcrp activities. The Bcrp-specific substrates were
      weak acids, whereas basic or neutral BCRP substrates were also P-glycoprotein
      substrates. These results suggest that BCRP limits the tissue penetration of
      xenobiotic compounds in the blood-brain and -testis barriers, but its in vivo
      importance is also modulated by P-glycoprotein activity.

PMID- 18322076
TI  - p38: the link between the kappa-opioid receptor and dysphoria.

PMID- 18322077
TI  - Timing neurogenesis and differentiation: insights from quantitative clonal
      analyses of cerebellar granule cells.
AB  - The cerebellum is an excellent model system to study how developmental programs
      give rise to exquisite neuronal circuits in the adult brain. Here, we describe
      our findings regarding granule cell neurogenesis and differentiation using the
      MADM method (mosaic analysis with double markers) in mice. By following the
      development of individual granule cell clones, we show that (1) granule cell
      precursors (GCPs) undergo predominantly symmetric division during postnatal
      development; (2) clonally related granule cells (GCs) exit the cell cycle within
      a narrow time window and stack their axons in the molecular layer in
      chronological order from deep to superficial sublayers; and (3) whereas the
      average GCP proliferation in the external granular layer is progressively slower
      as development proceeds, there is a rapid expansion of GCPs shortly before
      clonally related GCs exit the cell cycle. These properties produce GC clones that
      are distinct, each having a restricted axonal projection, but that are on average
      similar in cell number. We discuss possible developmental mechanisms and
      functional implications of these findings.

PMID- 18322078
TI  - Cannabinoid modulation of amygdala reactivity to social signals of threat in
      humans.
AB  - The cannabinoid (CB) system is a key neurochemical mediator of anxiety and fear
      learning in both animals and humans. The anxiolytic effects of delta(9)
      tetrahydrocannabinol (THC), the primary psychoactive ingredient in cannabis, are
      believed to be mediated through direct and selective agonism of CB(1) receptors
      localized within the basolateral amygdala, a critical brain region for threat
      perception. However, little is known about the effects of THC on amygdala
      reactivity in humans. We used functional magnetic resonance imaging and a well
      validated task to probe amygdala responses to threat signals in 16 healthy,
      recreational cannabis users after a double-blind crossover administration of THC
      or placebo. We found that THC significantly reduced amygdala reactivity to social
      signals of threat but did not affect activity in primary visual and motor cortex.
      The current findings fit well with the notion that THC and other cannabinoids may
      have an anxiolytic role in central mechanisms of fear behaviors and provide a
      rationale for exploring novel therapeutic strategies that target the cannabinoid
      system for disorders of anxiety and social fear.

PMID- 18322079
TI  - A vicious cycle involving release of heat shock protein 60 from injured cells and
      activation of toll-like receptor 4 mediates neurodegeneration in the CNS.
AB  - Infection, ischemia, trauma, and neoplasia elicit a similar inflammatory response
      in the CNS characterized by activation of microglia, the resident CNS monocyte.
      The molecular events leading from CNS injury to the activation of innate immunity
      is not well understood. We show here that the intracellular chaperone heat shock
      protein 60 (HSP60) serves as a signal of CNS injury by activating microglia
      through a toll-like receptor 4 (TLR4)-dependent and myeloid differentiation
      factor 88 (MyD88)-dependent pathway. HSP60 is released from CNS cells undergoing
      necrotic or apoptotic cell death and specifically binds to microglia. HSP60
      induced synthesis of neurotoxic nitric oxide by microglia is dependent on TLR4.
      HSP60 induces extensive axonal loss and neuronal death in CNS cultures from wild
      type but not TLR4 or MyD88 loss-of-function mutant mice. This is the first
      evidence of an endogenous molecular pathway common to many forms of neuronal
      injury that bidirectionally links CNS inflammation with neurodegeneration.

PMID- 18322080
TI  - Expression of nonclassical class I major histocompatibility genes defines a
      tripartite organization of the mouse vomeronasal system.
AB  - The epithelium of the mouse vomeronasal organ (VNO) consists of apical and basal
      layers of neuronal cell bodies. Vomeronasal sensory neurons (VSNs) with cell
      bodies in the basal layer express the G-protein subunit G alpha(o) and members of
      the V2R superfamily of vomeronasal receptor genes and project their axons to the
      posterior accessory bulb (AOB). V2R(+) VSNs also express particular patterns of a
      family of nine nonclassical class I major histocompatibility Mhc genes, the H2-Mv
      genes. The function of H2-Mv molecules remains unknown. H2-Mv molecules have been
      reported to be associated with V2R molecules and have been proposed to
      participate in pheromone detection. Here, we find that a substantial fraction of
      V2R(+) VSNs does not express these nine H2-Mv genes. The cell bodies of H2-Mv(+)
      and H2-Mv(-) VSNs reside in the lower and upper sublayers of the basal layer,
      respectively. This spatial segregation is maintained at the level of the AOB: H2
      Mv(+) and H2-Mv(-) VSNs project their axons to the posterior and anterior
      subdomains of the posterior AOB, respectively. By generating a C-terminal green
      fluorescent protein fusion protein with M10.2 in gene-targeted mice, we observe
      subcellular localization of M10.2 not only in dendrites but also in axons of
      VSNs. Our results reveal a tripartite organization of the VNO and AOB, question
      the generality of the requirement of these nine H2-Mv molecules for V2R surface
      expression, and suggest that H2-Mvs can function in both dendrites and axons.

PMID- 18322081
TI  - Genetic control of circuit function: Vsx1 and Irx5 transcription factors regulate
      contrast adaptation in the mouse retina.
AB  - Transcriptional programs guide the specification of neural cell types in the
      developing nervous system. However, it is unclear whether such programs also
      control specific aspects of neural circuit function at maturity. In the mammalian
      retina, Vsx1 and Irx5 transcription factors are present in a subset of bipolar
      interneurons that convey signals from photoreceptors to ganglion cells. The
      biased expression of Vsx1 and Irx5 in hyperpolarizing OFF compared with
      depolarizing ON bipolar cells suggests that these transcription factors may
      selectively regulate signal processing in OFF circuits. To test this hypothesis,
      we generated mice lacking both Vsx1 and Irx5. Bipolar cells in these mice were
      morphologically normal, but the expression of cell-specific markers in some OFF
      but not ON bipolar cells was reduced or absent. To assess visual function in
      Vsx1(-/-)Irx5(-/-) retinas, we recorded light responses from ensembles of retinal
      ganglion cells (RGCs). We first identified functional RGC types in control mice
      and describe their response properties and adaptation to temporal contrast using
      a simple linear-nonlinear model. We found that space-time receptive fields of
      RGCs are unchanged in Vsx1(-/-)Irx5(-/-) mice compared with control retinas. In
      contrast, response threshold, gain, and range were lowered in a cell-type
      specific manner in OFF but not ON RGCs in Vsx1(-/-)Irx5(-/-) retinas. Finally, we
      discovered that the ability to adapt to temporal contrast is greatly reduced in
      OFF RGCs in the double mutant, suggesting that Vsx1 and Irx5 control specific
      aspects of visual function in circuits of the mammalian retina.

PMID- 18322082
TI  - Functional imaging, spatial reconstruction, and biophysical analysis of a
      respiratory motor circuit isolated in vitro.
AB  - We combined real-time calcium-based neural activity imaging with whole-cell patch
      clamp recording techniques to map the spatial organization and analyze
      electrophysiological properties of respiratory neurons forming the circuit
      transmitting rhythmic drive from the pre-Botzinger complex (pre-BotC) through
      premotoneurons to hypoglossal (XII) motoneurons. Inspiratory pre-BotC neurons,
      XII premotoneurons (preMNs), and XII motoneurons (MNs) were retrogradely labeled
      with Ca(2+)-sensitive dye in neonatal rat in vitro brainstem slices. PreMN cell
      bodies were arrayed dorsomedially to pre-BotC neurons with little spatial
      overlap; axonal projections to MNs were ipsilateral. Inspiratory MNs were
      distributed in dorsal and ventral subnuclei of XII. Voltage-clamp recordings
      revealed that two currents, persistent sodium current (NaP) and K(+)-dominated
      leak current (Leak), primarily contribute to preMN/MN subthreshold current
      voltage relationships. NaP or Leak conductance densities in preMNs and MNs were
      not significantly different. We quantified preMN and MN action potential time
      course and spike frequency-current (f-I) relationships and found no significant
      differences in repetitive spiking dynamics, steady-state f-I gains, and
      afterpolarizing potentials. Rhythmic synaptic drive current densities were
      similar in preMNs and MNs. Our results indicate that, despite topographic and
      morphological differences, preMNs and MNs have some common intrinsic membrane,
      synaptic integration, and spiking properties that we postulate ensure fidelity of
      inspiratory drive transmission and conversion of synaptic drive into (pre)motor
      output. There also appears to be a common architectonic organization for some
      respiratory drive transmission circuits whereby many preMNs are spatially
      segregated from pre-BotC rhythm-generating neurons, which we hypothesize may
      facilitate downstream integration of convergent inputs for premotor pattern
      formation.

PMID- 18322083
TI  - Neurite outgrowth and in vivo sensory innervation mediated by a Ca(V)2.2-laminin
      beta 2 stop signal.
AB  - Axons and dendrites of developing neurons establish distributed innervation
      patterns enabling precise discrimination in sensory systems. We describe the role
      of the extracellular matrix molecule, laminin beta2, interacting with the
      Ca(V)2.2 calcium channel in establishing appropriate sensory innervation. In
      vivo, Ca(V)2.2 is expressed on the growth cones of Xenopus laevis sensory
      neurites and laminin beta2 is expressed in the skin. Culturing neurons on a
      laminin beta2 substrate inhibits neurite outgrowth in a specific and calcium
      dependent manner. Blocking signaling between laminin beta2 and Ca(V)2.2 leads to
      increased numbers of sensory terminals in vivo. These findings suggest that
      interactions between extracellular matrix molecules and calcium channels regulate
      connectivity in the developing nervous system.

PMID- 18322084
TI  - Transient D1 dopamine receptor expression on prefrontal cortex projection
      neurons: relationship to enhanced motivational salience of drug cues in
      adolescence.
AB  - Adolescence is a transitional period during development that is associated with a
      greater likelihood of addiction to drugs than any other age. In the prefrontal
      cortex (PFC), D(1) dopamine receptors mediate motivational salience attribution,
      which plays a role in addiction. Here, we investigated the relationship of age
      related D(1) dopamine receptor expression in the PFC with the maturation of
      cocaine place conditioning. Confocal microscopy revealed that retrogradely traced
      cortical output neurons to the nucleus accumbens express higher levels of D(1)
      receptors during adolescence compared with younger and older ages. D(1)
      expression does not change on GABAergic interneurons across age. Adolescent
      differences in D(1) expression occur independently of cortical-accumbens
      connectivity, which proliferates through adulthood. Behaviorally, adolescent rats
      are more sensitive to cocaine place conditioning than younger and older rats.
      However, microinjections of the D(1) antagonist SCH23390 into the PFC blocked
      adolescent place preferences, whereas microinjections of D(1) agonists dose
      dependently increased preferences for cocaine-associated environments previously
      not preferred by juveniles. These results suggest that the heightened expression
      of D(1) receptors on cortical-accumbens projections may help explain increased
      sensitivity to environmental events and addictive behaviors during adolescence,
      whereas the paucity of D(1)-expressing projections may reduce risk in juveniles.

PMID- 18322085
TI  - Variant brain-derived neurotrophic factor (Val66Met) alters adult olfactory bulb
      neurogenesis and spontaneous olfactory discrimination.
AB  - Neurogenesis, the division, migration, and differentiation of new neurons, occurs
      throughout life. Brain derived neurotrophic factor (BDNF) has been identified as
      a potential signaling molecule regulating neurogenesis in the subventricular zone
      (SVZ), but its functional consequences in vivo have not been well defined. We
      report marked and unexpected deficits in survival but not proliferation of newly
      born cells of adult knock-in mice containing a variant form of BDNF [a valine
      (Val) to methionine (Met) substitution at position 66 in the prodomain of BDNF
      (Val66Met)], a genetic mutation shown to lead to a selective impairment in
      activity-dependent BDNF secretion. Utilizing knock-out mouse lines, we identified
      BDNF and tyrosine receptor kinase B (TrkB) as the critical molecules for the
      observed impairments in neurogenesis, with p75 knock-out mice showing no effect
      on cell proliferation or survival. We then localized the activated form of TrkB
      to a discrete population of cells, type A migrating neuroblasts, and demonstrate
      a decrease in TrkB phosphorylation in the SVZ of Val66Met mutant mice. With these
      findings, we identify TrkB signaling, potentially through activity dependent
      release of BDNF, as a critical step in the survival of migrating neuroblasts.
      Utilizing a behavioral task shown to be sensitive to disruptions in olfactory
      bulb neurogenesis, we identified specific impairments in spontaneous olfactory
      discrimination, but not general olfactory sensitivity or habituation to olfactory
      stimuli in BDNF mutant mice. Through these observations, we have identified novel
      links between genetic variant BDNF and adult neurogenesis in vivo, which may
      contribute to significant impairments in olfactory function.

PMID- 18322086
TI  - Endothelin-1 regulates astrocyte proliferation and reactive gliosis via a JNK/c
      Jun signaling pathway.
AB  - Reactive gliosis is characterized by enhanced glial fibrillary acidic protein
      (GFAP) expression, cellular hypertrophy, and astrocyte proliferation. The
      cellular and molecular mechanisms underlying this process are still largely
      undefined. We investigated the role of endothelin-1 (ET-1) in reactive gliosis in
      corpus callosum after lysolecithin (LPC)-induced focal demyelination and in
      cultured astrocytes. We show that ET-1 levels are upregulated in demyelinated
      lesions within 5 d after LPC injection, together with enhanced astrocyte
      proliferation, GFAP expression, and JNK phosphorylation. Infusion of the pan-ET
      receptor (ET-R) antagonist Bosentan or the selective ET(B)-R antagonist BQ788
      into the corpus callosum prevented postlesion astrocyte proliferation and JNK
      phosphorylation. In cultured astrocytes, ET-1-induced activation of ET(B)-Rs
      promotes a reactive phenotype by enhancing both GFAP expression and astrocyte
      proliferation. In the same cells, ET-1 activates both JNK and p38MAPK pathways,
      and induces c-Jun expression at the mRNA and protein levels. By using selective
      pharmacological inhibitors, we also provide evidence that ET-1 induces astrocyte
      proliferation and GFAP expression through activation of ERK- and JNK-dependent
      pathways, consistent with the previous observation of ET-1-induced activation of
      ERK (Schinelli et al., 2001). Finally, we show by gain and loss of function that
      increased c-Jun expression enhances the proliferative response of astrocytes to
      ET-1, whereas c-jun siRNA prevents ET-1-induced cell proliferation. Our results
      indicate that the effects of ET-1 on astrocyte proliferation depend on c-Jun
      induction and activation through ERK- and JNK-dependent pathways, and suggest
      that ET-R-associated pathways might represent important targets to control
      reactive gliosis.

PMID- 18322087
TI  - Individual premotor drive pulses, not time-varying synergies, are the units of
      adjustment for limb trajectories constructed in spinal cord.
AB  - Complex actions may arise by combining simple motor primitives. Our studies
      support individual premotor drive pulses or bursts as execution primitives in
      spinal cord. Alternatively, the fundamental execution primitives at the segmental
      level could be time-varying synergies. To distinguish these hypotheses, we
      examined sensory feedback effects during targeted wiping organized in spinal
      cord. This behavior comprises three bursts. We tested (1) whether feedback
      altered the structure of individual premotor drive bursts or primitives, and (2)
      whether feedback differentially modulated different drive bursts or pulses in the
      three burst sequence. At least two of the three bursts would need to always be
      comodulated to support a time-varying synergy. We used selective muscle vibration
      to control spindle feedback from a single muscle (biceps/iliofibularis). The
      structures of premotor drive bursts were conserved. However, biceps vibration (1)
      scaled the amplitudes of two bursts coactivated during the initial phase of
      wiping independently of one another without altering their phase, and (2)
      independently phase regulated the third burst but preserved its amplitude. Thus,
      all three bursts were regulated separately. Durations were unaffected. The
      independent effects depended on (1) time of vibration during wiping, (2)
      frequency of vibration, and (3) limb configuration. Because each of the three
      bursts was independently modulated, these data strongly support execution using
      individual premotor bursts rather than time-varying synergies at the spinal level
      of motor organization. Our data show that both sensory feedback and central
      systems of the spinal cord act in concert to adjust the individual premotor
      bursts in support of the straight and unimodal wiping trajectory.

PMID- 18322088
TI  - Specificity of speech motor learning.
AB  - The idea that the brain controls movement using a neural representation of limb
      dynamics has been a dominant hypothesis in motor control research for well over a
      decade. Speech movements offer an unusual opportunity to test this proposal by
      means of an examination of transfer of learning between utterances that are to
      varying degrees matched on kinematics. If speech learning results in a
      generalizable dynamics representation, then, at the least, learning should
      transfer when similar movements are embedded in phonetically distinct utterances.
      We tested this idea using three different pairs of training and transfer
      utterances that substantially overlap kinematically. We find that, with these
      stimuli, speech learning is highly contextually sensitive and fails to transfer
      even to utterances that involve very similar movements. Speech learning appears
      to be extremely local, and the specificity of learning is incompatible with the
      idea that speech control involves a generalized dynamics representation.

PMID- 18322089
TI  - Dopamine receptor activation is required for corticostriatal spike-timing
      dependent plasticity.
AB  - Single action potentials (APs) backpropagate into the higher-order dendrites of
      striatal spiny projection neurons during cortically driven "up" states. The
      timing of these backpropagating APs relative to the arriving corticostriatal
      excitatory inputs determines changes in dendritic calcium concentration. The
      question arises to whether this spike-timing relative to cortical excitatory
      inputs can also induce synaptic plasticity at corticostriatal synapses. Here we
      show that timing of single postsynaptic APs relative to the cortically evoked
      EPSP determines both the direction and the strength of synaptic plasticity in
      spiny projection neurons. Single APs occurring 30 ms before the cortically evoked
      EPSP induced long-term depression (LTD), whereas APs occurring 10 ms after the
      EPSP induced long-term potentiation (LTP). The amount of plasticity decreased as
      the time between the APs and EPSPs was increased, with the resulting spike-timing
      window being broader for LTD than for LTP. In addition, we show that dopamine
      receptor activation is required for this spike-timing-dependent plasticity
      (STDP). Blocking dopamine D(1)/D(5) receptors prevented both LTD and LTP
      induction. In contrast, blocking dopamine D(2) receptors delayed, but did not
      prevent, LTD and sped induction of LTP. We conclude (1) that, in combination with
      cortical inputs, single APs evoked in spiny projection neurons can induce both
      LTP and LTD of the corticostriatal pathway; (2) that the strength and direction
      of these synaptic changes depend deterministically on the AP timing relative to
      the arriving cortical inputs; (3) that, whereas dopamine D(2) receptor activation
      modulates the initial phase of striatal STDP, dopamine D(1)/D(5) receptor
      activation is critically required for striatal STDP. Thus, the timing of APs
      relative to cortical inputs alone is not enough to induce corticostriatal
      plasticity, implying that ongoing activity does not affect synaptic strength
      unless dopamine receptors are activated.

PMID- 18322090
TI  - Generation of eupnea and sighs by a spatiochemically organized inspiratory
      network.
AB  - The discovery of the rhythmogenic pre-Botzinger complex (preBotC) inspiratory
      network, which remains active in a transverse brainstem slice, greatly increased
      the understanding of neural respiratory control. However, basic questions remain
      unanswered such as (1) What are the necessary and sufficient slice boundaries for
      a functional preBotC? (2) Is the minimal preBotC capable of reconfiguring between
      inspiratory-related patterns (e.g., fictive eupnea and sighs)? (3) How is preBotC
      activity affected by surrounding structures? Using newborn rat slices with
      systematically varied dimensions in physiological [K(+)] (3 mM), we found that a
      175 microm thickness is sufficient for generating inspiratory-related rhythms. In
      700-microm-thick slices with unilaterally exposed preBotC, a kernel <100 microm
      thick, centered 0.5 mm caudal to the facial nucleus, is necessary for rhythm
      generation. Slices containing this kernel plus caudal structures produced eupneic
      bursts of regular amplitude, whereas this kernel plus rostral tissue generated
      sighs, intermingled with eupneic bursts of variable amplitude ("eupnea-sigh
      pattern"). After spontaneous arrest of rhythm, substance-P or neurokinin-1 (NK1)
      receptor agonist induced the eupnea-sigh burst pattern in > or = 250-microm-thick
      slices, whereas thyrotropin-releasing hormone or phosphodiesterase-4 blockers
      evoked the eupnea burst pattern. Endogenous rhythm was depressed by NK1 receptor
      antagonism. Multineuronal Ca(2+) imaging revealed that preBotC neurons
      reconfigure between eupnea and eupnea-sigh burst patterns. We hypothesize a
      (gradient-like) spatiochemical organization of regions adjacent to the preBotC,
      such that a small preBotC inspiratory-related oscillator generates eupnea under
      the dominant influence of caudal structures or thyrotropin-releasing hormone-like
      transmitters but eupnea-sigh activity when the influence of rostral structures or
      substance-P-like transmitters predominates.

PMID- 18322091
TI  - Acetylcholinesterase expression in muscle is specifically controlled by a
      promoter-selective enhancesome in the first intron.
AB  - Mammalian acetylcholinesterase (AChE) gene expression is exquisitely regulated in
      target tissues and cells during differentiation. An intron located between the
      first and second exons governs a approximately 100-fold increase in AChE
      expression during myoblast to myotube differentiation in C2C12 cells. Regulation
      is confined to 255 bp of evolutionarily conserved sequence containing functional
      transcription factor consensus motifs that indirectly interact with the
      endogenous promoter. To examine control in vivo, this region was deleted by
      homologous recombination. The knock-out mouse is virtually devoid of AChE
      activity and its encoding mRNA in skeletal muscle, yet activities in brain and
      spinal cord innervating skeletal muscle are unaltered. The transcription factors
      MyoD and myocyte enhancer factor-2 appear to be responsible for muscle
      regulation. Selective control of AChE expression by this region is also found in
      hematopoietic lineages. Expression patterns in muscle and CNS neurons establish
      that virtually all AChE activity at the mammalian neuromuscular junction arises
      from skeletal muscle rather than from biosynthesis in the motoneuron cell body
      and axoplasmic transport.

PMID- 18322092
TI  - Neurodegeneration and motor dysfunction in a conditional model of Parkinson's
      disease.
AB  - Alpha-synuclein (alpha-syn) has been implicated in the pathogenesis of many
      neurodegenerative disorders, including Parkinson's disease. These disorders are
      characterized by various neurological and psychiatric symptoms based on
      progressive neuropathological alterations. Whether the neurodegenerative process
      might be halted or even reversed is presently unknown. Therefore, conditional
      mouse models are powerful tools to analyze the relationship between transgene
      expression and progression of the disease. To explore whether alpha-syn solely
      originates and further incites these alterations, we generated conditional mouse
      models by using the tet-regulatable system. Mice expressing high levels of human
      wild-type alpha-syn in midbrain and forebrain regions developed nigral and
      hippocampal neuropathology, including reduced neurogenesis and neurodegeneration
      in absence of fibrillary inclusions, leading to cognitive impairment and
      progressive motor decline. Turning off transgene expression in symptomatic mice
      halted progression but did not reverse the symptoms. Thus, our data suggest that
      approaches targeting alpha-syn-induced pathological pathways might be of benefit
      rather in early disease stages. Furthermore, alpha-syn-associated cytotoxicity is
      independent of filamentous inclusion body formation in our conditional mouse
      model.

PMID- 18322093
TI  - Transient receptor potential A1 is a sensory receptor for multiple products of
      oxidative stress.
AB  - Transient receptor potential A1 (TRPA1) is expressed in a subset of nociceptive
      sensory neurons where it acts as a sensor for environmental irritants, including
      acrolein, and some pungent plant ingredients such as allyl isothiocyanate and
      cinnamaldehyde. These exogenous compounds activate TRPA1 by covalent modification
      of cysteine residues. We have used electrophysiological methods and measurements
      of intracellular calcium concentration ([Ca(2+)](i)) to show that TRPA1 is
      activated by several classes of endogenous thiol-reactive molecules. TRPA1 was
      activated by hydrogen peroxide (H(2)O(2); EC(50), 230 microM), by endogenously
      occurring alkenyl aldehydes (EC(50): 4-hydroxynonenal 19.9 microM, 4-oxo-nonenal
      1.9 microM, 4-hydroxyhexenal 38.9 microM) and by the cyclopentenone
      prostaglandin, 15-deoxy-delta(12,14)-prostaglandin J(2) (15d-PGJ(2), EC(50): 5.6
      microM). The effect of H(2)O(2) was reversed by treatment with dithiothreitol
      indicating that H(2)O(2) acts by promoting the formation of disulfide bonds
      whereas the actions of the alkenyl aldehydes and 15d-PGJ(2) were not reversed,
      suggesting that these agents form Michael adducts. H(2)O(2) and the naturally
      occurring alkenyl aldehydes and 15d-PGJ(2) acted on a subset of isolated rat and
      mouse sensory neurons [approximately 25% of rat dorsal root ganglion (DRG) and
      approximately 50% of nodose ganglion neurons] to evoke a depolarizing inward
      current and an increase in [Ca(2+)](i) in TRPA1 expressing neurons. The abilities
      of H(2)O(2), alkenyl aldehydes and 15d-PGJ(2) to raise [Ca(2+)](i) in mouse DRG
      neurons were greatly reduced in neurons from trpa1(-/-) mice. Furthermore,
      intraplantar injection of either H(2)O(2) or 15d-PGJ2 evoked a nocifensive/pain
      response in wild-type mice, but not in trpa1(-/-) mice. These data demonstrate
      that multiple agents produced during episodes of oxidative stress can activate
      TRPA1 expressed in sensory neurons.

PMID- 18322094
TI  - Defects in breathing and thermoregulation in mice with near-complete absence of
      central serotonin neurons.
AB  - Serotonergic neurons project widely throughout the CNS and modulate many
      different brain functions. Particularly important, but controversial, are the
      contributions of serotonin (5-HT) neurons to respiratory and thermoregulatory
      control. To better define the roles of 5-HT neurons in breathing and
      thermoregulation, we took advantage of a unique conditional knock-out mouse in
      which Lmx1b is genetically deleted in Pet1-expressing cells (Lmx1b(f/f/p)),
      resulting in near-complete absence of central 5-HT neurons. Here, we show that
      the hypercapnic ventilatory response in adult Lmx1b(f/f/p) mice was decreased by
      50% compared with wild-type mice, whereas baseline ventilation and the hypoxic
      ventilatory response were normal. In addition, Lmx1b(f/f/p) mice rapidly became
      hypothermic when exposed to an ambient temperature of 4 degrees C, decreasing
      core temperature to 30 degrees C within 120 min. This failure of thermoregulation
      was caused by impaired shivering and nonshivering thermogenesis, whereas
      thermosensory perception and heat conservation were normal. Finally,
      intracerebroventricular infusion of 5-HT stimulated baseline ventilation, and
      rescued the blunted hypercapnic ventilatory response. These data identify a
      previously unrecognized role of 5-HT neurons in the CO(2) chemoreflex, whereby
      they enhance the response of the rest of the respiratory network to CO(2). We
      conclude that the proper function of the 5-HT system is particularly important
      under conditions of environmental stress and contributes significantly to the
      hypercapnic ventilatory response and thermoregulatory cold defense.

PMID- 18322095
TI  - Botzinger expiratory-augmenting neurons and the parafacial respiratory group.
AB  - In neonatal rat brains in vitro, the rostral ventral respiratory column (rVRC)
      contains neurons that burst just before the phrenic nerve discharge (PND) and
      rebound after inspiration (pre-I neurons). These neurons, called parafacial
      respiratory group (pfRG), have been interpreted as a master inspiratory
      oscillator, an expiratory rhythm generator or simply as neonatal precursors of
      retrotrapezoid (RTN) chemoreceptor neurons. pfRG neurons have not been identified
      in adults, and their phenotype is unknown. Here, we confirm that the rVRC
      normally lacks pre-I neurons in adult anesthetized rats. However, we show that,
      during hypercapnic hypoxia, a population of rVRC expiratory-augmenting (E-AUG)
      neurons consistently develops a pre-I discharge. These cells reside in the
      Botzinger region of the rVRC, they express glycine-transporter-2, and their axons
      arborize throughout the VRC. Hypoxia triggers an identical pre-I pattern in
      retroambigual expiratory bulbospinal neurons, but this pattern is not elicited in
      Botzinger expiratory-decrementing neurons, Botzinger inspiratory neurons, RTN
      neurons, and blood pressure-regulating neurons. In conclusion, under hypoxia in
      vivo, abdominal expiratory premotor neurons of adult rats develop a pre-I pattern
      reminiscent of that observed in neonate brainstems in vitro. In the rVRC of adult
      rats, pre-I cells include selected rhythmogenic neurons (glycinergic Botzinger
      neurons) but not RTN chemoreceptors. We suggest that the pfRG may not be an
      independent rhythm generator but a heterogeneous collection of E-AUG neurons
      (glycinergic Botzinger neurons, possibly facial motor and premotor neurons), the
      discharge of which becomes preinspiratory under specific experimental conditions
      resulting from, in part, a prolonged and intensified activity of postinspiratory
      neurons.

PMID- 18322096
TI  - Withdrawal from cocaine self-administration normalizes deficits in proliferation
      and enhances maturity of adult-generated hippocampal neurons.
AB  - Relapse, a major problem in the treatment of cocaine addiction, is proposed to
      result in part from neuroadaptations in the hippocampus. We examined how a
      mediator of hippocampal neuroplasticity, adult neurogenesis in the subgranular
      zone (SGZ), was regulated by cocaine self-administration (CSA), and whether these
      changes were reversed by 4 weeks of withdrawal (CSA-WD) versus continued cocaine
      self-administration (CSA-CONT). Rats self-administered intravenous cocaine or
      saline for 3 weeks and were killed 2 h (CSA) or 4 weeks (CSA-WD, CSA-CONT) after
      injection with the S-phase marker bromodeoxyuridine (BrdU). Cells in several
      stages of adult neurogenesis were quantified: proliferating cells labeled by BrdU
      (2 h) or Ki-67; immature neurons labeled by doublecortin; and adult-generated
      neurons labeled with BrdU (4 weeks) and the mature neuronal marker NeuN. CSA
      decreased proliferation in both the SGZ and the subventricular zone (SVZ), a
      source of adult-generated olfactory neurons, changes reversed by CSA-WD.
      Unexpectedly, CSA-WD and CSA-CONT resulted in more immature doublecortin
      immunopositive (+) neurons in the posterior SGZ and a normal number of adult
      generated BrdU+ neurons in the SGZ, suggesting an enduring impact of CSA
      regardless of whether cocaine intake was stopped or continued. However, only CSA
      WD rats had more adult-generated neurons with punctate BrdU staining, an
      indicator of enhanced maturity. These data suggest a mechanism for the cognitive
      and olfactory deficits seen in cocaine addicts, and further suggest that adult
      generated neurons should be considered for their potential role in cocaine
      addiction and hippocampal-mediated relapse after cocaine withdrawal.

PMID- 18322097
TI  - Subunit-specific trafficking of GABA(A) receptors during status epilepticus.
AB  - It is proposed that a reduced surface expression of GABA(A) receptors (GABARs)
      contributes to the pathogenesis of status epilepticus (SE), a condition
      characterized by prolonged seizures. This hypothesis was based on the finding
      that prolonged epileptiform bursting (repetitive bursts of prolonged
      depolarizations with superimposed action potentials) in cultures of dissociated
      hippocampal pyramidal neurons (dissociated cultures) results in the increased
      intracellular accumulation of GABARs. However, it is not known whether this rapid
      modification in the surface-expressed GABAR pool results from selective, subunit
      dependent or nonselective, subunit-independent internalization of GABARs. In
      hippocampal slices obtained from animals undergoing prolonged SE (SE-treated
      slices), we found that the surface expression of the GABAR beta2/3 and gamma2
      subunits was reduced, whereas that of the delta subunit was not. Complementary
      electrophysiological recordings from dentate granule cells in SE-treated slices
      demonstrated a reduction in GABAR-mediated synaptic inhibition, but not tonic
      inhibition. A reduction in the surface expression of the gamma2 subunit, but not
      the delta subunit was also observed in dissociated cultures and organotypic
      hippocampal slice cultures when incubated in an elevated KCl external medium or
      an elevated KCl external medium supplemented with NMDA, respectively. Additional
      studies demonstrated that the reduction in the surface expression of the gamma2
      subunit was independent of direct ligand binding of the GABAR. These findings
      demonstrate that the regulation of surface-expressed GABAR pool during SE is
      subunit-specific and occurs independent of ligand binding. The differential
      modulation of the surface expression of GABARs during SE has potential
      implications for the treatment of this neurological emergency.

PMID- 18322098
TI  - A hierarchy of temporal receptive windows in human cortex.
AB  - Real-world events unfold at different time scales and, therefore, cognitive and
      neuronal processes must likewise occur at different time scales. We present a
      novel procedure that identifies brain regions responsive to sensory information
      accumulated over different time scales. We measured functional magnetic resonance
      imaging activity while observers viewed silent films presented forward, backward,
      or piecewise-scrambled in time. Early visual areas (e.g., primary visual cortex
      and the motion-sensitive area MT+) exhibited high response reliability regardless
      of disruptions in temporal structure. In contrast, the reliability of responses
      in several higher brain areas, including the superior temporal sulcus (STS),
      precuneus, posterior lateral sulcus (LS), temporal parietal junction (TPJ), and
      frontal eye field (FEF), was affected by information accumulated over longer time
      scales. These regions showed highly reproducible responses for repeated forward,
      but not for backward or piecewise-scrambled presentations. Moreover, these
      regions exhibited marked differences in temporal characteristics, with LS, TPJ,
      and FEF responses depending on information accumulated over longer durations
      (approximately 36 s) than STS and precuneus (approximately 12 s). We conclude
      that, similar to the known cortical hierarchy of spatial receptive fields, there
      is a hierarchy of progressively longer temporal receptive windows in the human
      brain.

PMID- 18322099
TI  - Early neuronal and glial fate restriction of embryonic neural stem cells.
AB  - The question of how neurons and glial cells are generated during the development
      of the CNS has over time led to two alternative models: either neuroepithelial
      cells are capable of giving rise to neurons first and to glial cells at a later
      stage (switching model), or they are intrinsically committed to generate one or
      the other (segregating model). Using the developing diencephalon as a model and
      by selecting a subpopulation of ventricular cells, we analyzed both in vitro,
      using clonal analysis, and in vivo, using inducible Cre/loxP fate mapping, the
      fate of neuroepithelial and radial glial cells generated at different time points
      during embryonic development. We found that, during neurogenic periods [embryonic
      day 9.5 (E9.5) to 12.5], proteolipid protein (plp)-expressing cells were lineage
      restricted neuronal precursors, but later in embryogenesis, during gliogenic
      periods (E13.5 to early postnatal), plp-expressing cells were lineage-restricted
      glial precursors. In addition, we show that glial cells forming at E13.5 arise
      from a new pool of neuroepithelial progenitors distinct from neuronal progenitors
      cells, which lends support to the segregating model.

PMID- 18322100
TI  - Action potential-independent and nicotinic receptor-mediated concerted release of
      multiple quanta at hippocampal CA3-mossy fiber synapses.
AB  - Presynaptic action potential-independent transmitter release is a potential means
      of information transfer across synapses. We show that in the hippocampal mossy
      fiber boutons, activation of the alpha7-subtype of nicotinic acetylcholine
      receptors (alpha7-nAChRs) results in a large increase in the amplitude of
      spontaneous events, resulting from concerted release of multiple quanta from the
      mossy fiber boutons. This amplitude increase is abolished at low temperatures.
      Activation of alpha7-nAChRs causes a rise in intraterminal calcium at mossy fiber
      boutons, involving ryanodine receptors. Regulation of concerted release requires
      the subsequent activation of presynaptic calcium/calmodulin-dependent protein
      kinase II (CaMKII). Activation of CaMKII is required to drive presynaptic action
      potential-independent transmission at the mossy fiber-CA3 pyramidal cell synapse.
      The effects of alpha7-nAChR activation are mediated by biologically relevant
      doses of nicotine. Our results demonstrate a novel form of synaptic plasticity
      mediated by presynaptic alpha7-nAChRs and store calcium that is temporally
      different and might respond to a different history of synaptic activity than that
      mediated by incoming action potentials.

PMID- 18322101
TI  - Synergistic neuroprotective effects of lithium and valproic acid or other histone
      deacetylase inhibitors in neurons: roles of glycogen synthase kinase-3
      inhibition.
AB  - Lithium and valproic acid (VPA) are two primary drugs used to treat bipolar mood
      disorder and have frequently been used in combination to treat bipolar patients
      resistant to monotherapy with either drug. Lithium, a glycogen synthase kinase-3
      (GSK-3) inhibitor, and VPA, a histone deacetylase (HDAC) inhibitor, have
      neuroprotective effects. The present study was undertaken to demonstrate
      synergistic neuroprotective effects when both drugs were coadministered.
      Pretreatment of aging cerebellar granule cells with lithium or VPA alone provided
      little or no neuroprotection against glutamate-induced cell death. However,
      copresence of both drugs resulted in complete blockade of glutamate
      excitotoxicity. Combined treatment with lithium and VPA potentiated serine
      phosphorylation of GSK-3 alpha and beta isoforms and inhibition of GSK-3 enzyme
      activity. Transfection with GSK-3alpha small interfering RNA (siRNA) and/or GSK
      3beta siRNA mimicked the ability of lithium to induce synergistic protection with
      VPA. HDAC1 siRNA or other HDAC inhibitors (phenylbutyrate, sodium butyrate or
      trichostatin A) also caused synergistic neuroprotection together with lithium.
      Moreover, combination of lithium and HDAC inhibitors potentiated beta-catenin
      dependent, Lef/Tcf-mediated transcriptional activity. An additive increase in GSK
      3 serine phosphorylation was also observed in mice chronically treated with
      lithium and VPA. Together, for the first time, our results demonstrate
      synergistic neuroprotective effects of lithium and HDAC inhibitors and suggest
      that GSK-3 inhibition is a likely molecular target for the synergistic
      neuroprotection. Our results may have implications for the combined use of
      lithium and VPA in treating bipolar disorder. Additionally, combined use of both
      drugs may be warranted for clinical trials to treat glutamate-related
      neurodegenerative diseases.

PMID- 18322102
TI  - Effector immediate-early gene arc in the amygdala plays a critical role in
      alcoholism.
AB  - The immediate early gene, activity-regulated cytoskeleton-associated protein
      (Arc), has been implicated in synaptic plasticity. However, the role of Arc in
      alcoholism is unknown. Here, we report that the anxiolytic effects of acute
      ethanol were associated with increased brain-derived neurotrophic factor (BDNF)
      and tyrosine kinase B (trkB) expression, increased phosphorylation of
      extracellular signal-regulated kinases 1/2 (Erk1/2), Elk-1, and cAMP responsive
      element-binding protein (CREB), increased Arc expression, and increased dendritic
      spine density (DSD) in both the central amygdala (CeA) and medial amygdala (MeA)
      but not in the basolateral amygdala (BLA) of rats. Conversely, the anxiogenic
      effects of withdrawal after long-term ethanol exposure were associated with
      decreased BDNF and trkB expression, decreased phosphorylation of Erk1/2, Elk-1,
      and CREB, decreased Arc expression, and decreased DSD in both the CeA and MeA but
      not in the BLA of rats. We also showed that BDNF infusion into the CeA normalized
      phosphorylation of Erk1/2, Elk-1, and CREB, and normalized Arc expression,
      thereby protecting against the onset of ethanol withdrawal-related anxiety. We
      further demonstrated that arresting Arc expression in the CeA decreased DSD,
      thereby increasing anxiety-like and alcohol-drinking behaviors in control rats.
      These results revealed that BDNF-Arc signaling and the associated DSD in the CeA,
      and possibly in the MeA, may be involved in the molecular processes of alcohol
      dependence and comorbidity of anxiety and alcohol-drinking behaviors.

PMID- 18322103
TI  - PKC-induced intracellular trafficking of Ca(V)2 precedes its rapid recruitment to
      the plasma membrane.
AB  - Activation of protein kinase C (PKC) potentiates secretion in Aplysia peptidergic
      neurons, in part by inducing new sites for peptide release at growth cone
      terminals. The mechanisms by which ion channels are trafficked to such sites are,
      however, not well understood. We now show that PKC activation rapidly recruits
      new Ca(V)2 subunits to the plasma membrane, and that recruitment is blocked by
      latrunculin B, an inhibitor of actin polymerization. In contrast, inhibition of
      microtubule polymerization selectively prevents the appearance of Ca(V)2 subunits
      only at the distal edge of the growth cone. In resting neurons, Ca(V)2-containing
      organelles reside in the central region of growth cones, but are absent from
      distal lamellipodia. After activation of PKC, these organelles are transported on
      microtubules to the lamellipodium. The ability to traffic to the most distal
      sites of channel insertion inside the lamellipodium does, therefore, not require
      intact actin but requires intact microtubules. Only after activation of PKC do
      Ca(V)2 channels associate with actin and undergo insertion into the plasma
      membrane.

PMID- 18322104
TI  - Bottom-up activation of the vocal motor forebrain by the respiratory brainstem.
AB  - Brainstem motor structures send output commands to the periphery and are
      dynamically modulated by telencephalic inputs. Little is known, however, about
      ascending brainstem control of forebrain motor structures. Here, we provide the
      first evidence for bottom-up activation of forebrain motor centers by the
      respiratory brainstem. We show that, in the avian vocal control system,
      activation of the brainstem inspiratory nucleus paraambigualus (PAm), a likely
      homolog of the mammalian rostral ventral respiratory group, can drive neural
      activity bilaterally in the forebrain vocal control nuclei HVC (used as a proper
      name) and the robust nucleus of the arcopallium (RA). Furthermore, this
      activation is abolished by lesions of nucleus uvaeformis (Uva), a thalamic
      nucleus necessary for song production. We identify a type of bursting neuron
      within PAm whose activity is correlated, in an Uva dependent manner, to bursting
      activity in RA, rather than to the respiratory rhythm, and is robustly active
      during the production of stimulus evoked vocalizations. Because this ascending
      input results in cross-hemisphere activation, our results suggest a crucial role
      for the respiratory brainstem in coordinating forebrain motor centers during
      vocal production.

PMID- 18322105
TI  - Interplay between cyclin-dependent kinase 5 and glycogen synthase kinase 3 beta
      mediated by neuregulin signaling leads to differential effects on tau
      phosphorylation and amyloid precursor protein processing.
AB  - Cyclin-dependent kinase 5 (cdk5) and glycogen synthase kinase 3beta (GSK3beta)
      have been implicated in pathogenic processes associated with Alzheimer's disease
      because both kinases regulate tau hyperphosphorylation and enhance amyloid
      precursor protein (APP) processing leading to an increase in amyloid beta (Abeta)
      production. Here we show that young p25 overexpressing mice have enhanced cdk5
      activity but reduced GSK3beta activity attributable to phosphorylation at the
      inhibitory GSK3beta-serine 9 (GSK3beta-S9) site. Phosphorylation at this site was
      mediated by enhanced activity of the neuregulin receptor complex, ErbB, and
      activation of the downstream phosphatidylinositol 3 kinase/Akt pathway. Young p25
      mice had elevated Abeta peptide levels, but phospho-tau levels were decreased
      overall. Thus, cdk5 appears to play a dominant role in the regulation of
      amyloidogenic APP processing, whereas GSK3beta plays a dominant role in overall
      tau phosphorylation. In older mice, GSK3beta inhibitory phosphorylation at S9 was
      reduced relative to young mice. Abeta peptide levels were still elevated but
      phospho-tau levels were either unchanged or showed a trend to increase,
      suggesting that GSK3beta activity increases with aging. Inhibition of cdk5 by a
      specific inhibitor reduced cdk5 activity in p25 mice, leading to reduced Abeta
      production in both young and old mice. However, in young mice, cdk5 inhibition
      reversed GSK3beta inhibition, leading to an increase in overall tau
      phosphorylation. When cdk5 inhibitor was administered to very old, nontransgenic
      mice, inhibition of cdk5 reduced Abeta levels, and phospho-tau levels showed a
      trend to increase. Thus, cdk5 inhibitors may not be effective in targeting tau
      phosphorylation in the elderly.

PMID- 18322106
TI  - D1-like dopamine receptor activation modulates GABAergic inhibition but not
      electrical coupling between neocortical fast-spiking interneurons.
AB  - Dopamine, acting through D(1) receptors, is thought to play an important role in
      cognitive functions of the frontal cortex such as working memory. D(1) receptors
      are widely expressed in fast-spiking (FS) interneurons, a prominent class of
      inhibitory cells that exert a powerful control of neuronal firing through
      proximal synapses on their postsynaptic targets. FS cells are extensively
      mutually interconnected by both GABA(A) receptor-mediated synapses and gap
      junction-mediated electrical synapses, and networks of FS cells play a crucial
      role in the generation of rhythmic synchronous activity. Although recent studies
      have documented the effects of dopamine modulation of neocortical synaptic
      connections among excitatory cells and between excitatory and various inhibitory
      cells, the effects of dopamine receptor activation on GABAergic and electrical
      interactions among FS cells is not known. To resolve this, we recorded from pairs
      of FS cells in the infragranular layers of mouse neocortical slices and tested
      the effects of D(1)-like (D(1)/D(5)) receptor activation on these connections. We
      found that D(1)-like receptor activation modulated GABAergic but not electrical
      connections between them. A D(1)-like receptor agonist preserved the strength of
      electrical coupling but reduced the amplitude of IPSPs and IPSCs between FS
      cells. Our results suggest that D(1)-like receptor activation has synapse
      specific effects within networks of FS cells, with potential implications for the
      generation of rhythmic activity in the neocortex.

PMID- 18322107
TI  - Cholinergic deafferentation of prefrontal cortex increases sensitivity to cross
      modal distractors during a sustained attention task.
AB  - The effects of restricted cholinergic deafferentation of prefrontal cortex in
      rats on sustained attention were assessed. Attentional demands were increased by
      presentation of distractor stimuli in a different modality (auditory) or the same
      modality (visual) as target stimuli. Additionally, the effects of the regularity
      of the distractor on rats' ability to disregard this stimulus were assessed by
      testing different frequencies of stimuli for each modality. Cholinergically
      lesioned rats were more sensitive to the effects of auditory distractors than
      nonlesioned rats, whereas visual distractors of any frequency potently impaired
      the performance of all subjects. The effects of the auditory stimuli on
      attentional performance varied depending on the frequency of the tone. A tone
      with a predictable pattern enhanced signal detection in all rats. An irregular
      tone selectively impaired performance of rats with cholinergic lesions.
      Additional tests suggest that rats use the regular tone to time when to attend.
      Lesioned rats were impaired when the regular tone was presented with a more
      variable intertrial interval in a subsequent testing session, suggesting
      impairments in top-down control. In addition to changes in top-down control of
      attention, differential effects on performance based on the regularity of the
      tone suggest that stimulus properties encoded by bottom-up processes are also
      altered after lesioning. The current data suggest that cholinergic
      deafferentation of prefrontal cortex alters top-down and bottom-up processing of
      stimuli.

PMID- 18322108
TI  - Extinction of a classically conditioned response: red nucleus and interpositus.
AB  - It is well established that the cerebellum and its associated circuitry are
      essential for classical conditioning of the eyeblink response and other discrete
      motor responses (e.g., limb flexion, head turn, etc.) learned with an aversive
      unconditioned stimulus. However, brain mechanisms underlying extinction of these
      responses are still relatively unclear. Behavioral studies have demonstrated
      extinction to be an active learning process distinct from acquisition.
      Accordingly, this current understanding of extinction has guided neural studies
      that have tried to identify possible brain structures that could support this new
      learning. However, whether extinction engages the same brain sites necessary for
      acquisition is not yet clear. This poses an overriding problem for understanding
      brain mechanisms necessary for extinction because such analysis cannot be done
      without first identifying brain sites and pathways involved in this phenomenon.
      Equally elusive is the validity of a behavioral theory of extinction that can
      account for the properties of extinction. In this study, we looked at the
      involvement of the interpositus and the red nucleus in extinction. Results show
      that, although inactivation of both nuclei blocks response expression, only
      inactivation of the interpositus has a detrimental effect on extinction.
      Moreover, this detrimental effect was completely removed when inactivation of the
      interpositus was paired with electrical stimulation of the red nucleus. These
      findings speak to the important role of cerebellar structures in the extinction
      of discrete motor responses and provide important insight as to the validity of a
      particular theory of extinction.

PMID- 18322109
TI  - Competitive and noncompetitive odorant interactions in the early neural coding of
      odorant mixtures.
AB  - Most olfactory receptor neurons (ORNs) express a single type of olfactory
      receptor that is differentially sensitive to a wide variety of odorant molecules.
      The diversity of possible odorant-receptor interactions raises challenging
      problems for the coding of complex mixtures of many odorants, which make up the
      vast majority of real world odors. Pure competition, the simplest kind of
      interaction, arises when two or more agonists can bind to the main receptor site,
      which triggers receptor activation, although only one can be bound at a time.
      Noncompetitive effects may result from various mechanisms, including agonist
      binding to another site, which modifies the receptor properties at the main
      binding site. Here, we investigated the electrophysiological responses of rat
      ORNs in vivo to odorant agonists and their binary mixtures and interpreted them
      in the framework of a quantitative model of competitive interaction between
      odorants. We found that this model accounts for all concentration-response curves
      obtained with single odorants and for about half of those obtained with binary
      mixtures. In the other half, the shifts of curves along the concentration axis
      and the changes of maximal responses with respect to model predictions, indicate
      that noncompetitive interactions occur and can modulate olfactory receptors. We
      conclude that, because of their high frequency, the noncompetitive interactions
      play a major role in the neural coding of natural odorant mixtures. This finding
      implies that the CNS activity caused by mixtures will not be easily analyzed into
      components, and that mixture responses will be difficult to generalize across
      concentration.

PMID- 18322110
TI  - Neural dissociation between visual awareness and spatial attention.
AB  - To what extent does what we consciously see depend on where we attend to?
      Psychologists have long stressed the tight relationship between visual awareness
      and spatial attention at the behavioral level. However, the amount of overlap
      between their neural correlates remains a matter of debate. We recorded
      magnetoencephalographic signals while human subjects attended toward or away from
      faint stimuli that were reported as consciously seen only half of the time.
      Visually identical stimuli could thus be attended or not and consciously seen or
      not. Although attended stimuli were consciously seen slightly more often than
      unattended ones, the factorial analysis of stimulus-induced oscillatory brain
      activity revealed distinct and independent neural correlates of visual awareness
      and spatial attention at different frequencies in the gamma range (30-150 Hz).
      Whether attended or not, consciously seen stimuli induced increased mid-frequency
      gamma-band activity over the contralateral visual cortex, whereas spatial
      attention modulated high-frequency gamma-band activity in response to both
      consciously seen and unseen stimuli. A parametric analysis of the data at the
      single-trial level confirmed that the awareness-related mid-frequency activity
      drove the seen-unseen decision but also revealed a small influence of the
      attention-related high-frequency activity on the decision. These results suggest
      that subjective visual experience is shaped by the cumulative contribution of two
      processes operating independently at the neural level, one reflecting visual
      awareness per se and the other reflecting spatial attention.

PMID- 18322111
TI  - Perception of the role of nuclear medicine in clinical practice in Nigeria.

PMID- 18322114
TI  - Working together to create the future.

PMID- 18322116
TI  - Consensus report on gastric emptying: what's needed to prevent tarnishing a gold
      standard?

PMID- 18322117
TI  - The promise of locoregional radiopharmaceutical therapy: will it ever be
      realized?

PMID- 18322118
TI  - Current and potential applications of clinical 13C MR spectroscopy.
AB  - In this article, the current and potential clinical roles of (13)C magnetic
      resonance spectroscopy (MRS) and (13)C magnetic resonance spectroscopic imaging
      are presented, with a focus on applications to prostate cancer and hyperpolarized
      (13)C spectroscopic imaging. The advantages of (13)C MRS have been its chemical
      specificity and lack of background signal, with the major disadvantage being its
      inherently low sensitivity and the subsequent inability to acquire data at a high
      enough spatial and temporal resolution to be routinely applicable in the clinic.
      The approaches to improving the sensitivity of (13)C spectroscopy have been to
      perform proton decoupling and to use endogenous (13)C-labeled or enhanced
      metabolic substrates. With these nominal increases in signal-to-noise ratio,
      (13)C MRS using labeled metabolic substrates has shown diagnostic promise in
      patients and has been approved by the Food and Drug Administration. The
      development of technology that applies dynamic nuclear polarization to generate
      hyperpolarized (13)C-labeled metabolic substrates, and the development of a
      process for delivering them into living subjects, have totally changed the
      clinical potential of MRS of (13)C-labeled metabolic substrates. Preliminary
      preclinical studies in a model of prostate cancer have demonstrated the potential
      clinical utility of hyperpolarized (13)C MRS.

PMID- 18322119
TI  - VP-PET: a new imaging modality?

PMID- 18322120
TI  - Nuclear cardiac stress testing in the era of molecular medicine.
AB  - The objective of cardiac stress testing is to detect coronary artery disease
      (CAD) and to prevent future adverse events, such as myocardial infarction or
      death. The progression from electrocardiographically based stress testing to
      current SPECT and PET technologies has brought improvements in diagnostic
      efficacy and resolution. Myocardial perfusion imaging facilitates management of
      CAD in elective and acute settings by providing valuable diagnostic and
      prognostic information. Hybrid PET/CT and SPECT/CT systems impart complementary
      information of coronary anatomy and its physiologic significance on blood flow
      reserve. In the current era, diagnosis and treatment of cardiovascular disease is
      increasingly defined by underlying molecular and genomic aberrations rather than
      by clinical signs and symptoms alone. Nuclear imaging is uniquely primed to
      exploit the targeting of expressed cell-surface molecules and intracellular
      processes of cardiovascular disease and to foster the development of innovative
      therapeutic interventions in the future.

PMID- 18322121
TI  - The use of photovoice as a method of facilitating deliberation.
AB  - Efforts have been made in one rural Appalachian county to broaden local
      participation in a community health assessment. Through a series of community
      forums and a photovoice project, residents named community health needs and
      assets, framed potential solutions, and selected possible action steps to improve
      the local health status. Photographs and narratives from the photovoice project
      supplemented information from preliminary health forums to devise a framework of
      possible solutions to the identified health problems. Analysis of forum
      transcripts suggests that participants who used an issue guide that used
      photovoice images and stories were able to transition from broad approaches of
      change to specific action steps more than participants in other forums who used a
      more traditional forum issue guide. Community members are more easily able to
      identify solutions to local health issues when forum discussions are informed by
      local images and narratives.

PMID- 18322122
TI  - Explaining and treating violent behavior.

PMID- 18322123
TI  - Men's behaviour towards prostate cancer screening.

PMID- 18322124
TI  - Management of toxic epidermal necrolysis and related syndromes.
AB  - Toxic epidermal necrolysis and Stevens-Johnson syndrome are rare and life
      threatening diseases that often configure as medical emergencies. The majority of
      cases are drug reactions. The clinical picture is one of widespread epidermal
      necrosis and mucosal erosions. Treatment is largely supportive and must be
      provided in an appropriate environment. The role of steroids and other potential
      disease-modifying therapies has yet to be fully established by controlled
      studies. The significant mortality associated with these conditions dictates that
      an understanding of these conditions is essential for all doctors.

PMID- 18322126
TI  - Thrombolysis or primary angioplasty? Reperfusion therapy for myocardial
      infarction in the UK.
AB  - Intravenous thrombolysis and percutaneous coronary intervention (PCI) are
      alternative treatment options for coronary reperfusion in acute myocardial
      infarction. Recent trials and meta-analyses have produced increasing evidence
      that primary coronary intervention produces better long-term outcomes for the
      treatment of acute myocardial infarction. Most of these studies, however, were
      performed in US or European healthcare systems and may not be directly
      transferable to an NHS setting. The widespread introduction of primary PCI would
      have major implications for the organisation of healthcare provision within the
      UK. An alternative to PCI that may produce similar outcomes at a reduced cost
      might be early (pre-hospital) administration of thrombolysis. In an era of
      unprecedented financial attention, the importance of interventions that are
      simultaneously beneficial to the patient and economical to the NHS has never been
      more important. The evidence base for primary PCI and its possible use in the NHS
      are discussed.

PMID- 18322127
TI  - Follicular variant of papillary thyroid carcinoma: a diagnostic challenge for
      clinicians and pathologists.
AB  - The follicular variant of papillary thyroid carcinoma (FVPTC) presents a type of
      papillary thyroid cancer that has created continuous diagnosis and treatment
      controversies among clinicians and pathologists. In this review, we describe the
      nomenclature, the clinical features, diagnostic problems and the molecular
      biology of FVPTC. It is important for clinicians to understand this entity as the
      diagnosis and management of this group of patient may be different from other
      patients with conventional PTC. The literature suggests that FVPTC behaves in a
      way similar, clinically, to conventional papillary thyroid carcinoma. However,
      there are some genotypic differences which may characterise this neoplasm. These
      parameters may account for the phenotypic variation described by some scientists
      in this type of cancer. Further understanding can only be achieved by defining
      strict pathological criteria, in-depth study of the molecular biology and long
      term follow-up of the optional patients with FVPTC.

PMID- 18322128
TI  - New methods for improved evaluation of patients with suspected acute coronary
      syndrome in the emergency department.
AB  - This paper aims to identify and review new and unproven emergency department (ED)
      methods for improved evaluation in cases of suspected acute coronary syndrome
      (ACS). Systematic news coverage through PubMed from 2000 to 2006 identified
      papers on new methods for ED assessment of patients with suspected ACS. Articles
      found described decision support models, new ECG methods, new biomarkers and
      point-of-care testing, cardiac imaging, immediate exercise tests and the chest
      pain unit concept. None of these new methods is likely to be the perfect
      solution, and the best strategy today is therefore a combination of modern
      methods, where the optimal protocol depends on local resources and expertise.
      With a suitable combination of new methods, it is likely that more patients can
      be managed as outpatients, that length of stay can be shortened for those
      admitted, and that some patients with ACS can get earlier treatment.

PMID- 18322129
TI  - Recent epidemiological changes in meningococcal disease may be due to the
      displacement of serogroup A by serogroup C in Hefei City, China.
AB  - OBJECTIVES: To determine the change in epidemiological characteristics of
      meningococcal disease in the Hefei City area and to provide valuable information
      for developing timely and appropriate public health interventions. METHODS:
      Meningococcal disease was identified according to the National Disease
      Surveillance System. Data were collected using standardised questionnaires.
      Serological and bacteria culture testing was performed on cerebrospinal fluid and
      serum specimens from suspected cases for evidence of Neisseria meningitidis
      infection. RESULTS: From July 2003 to June 2007, meningococcal disease was
      confirmed in 386 cases in the total population. This worked out at an annual
      incidence of 1.19-2.86 per 100,000 population, which was significantly higher
      than that in 2002-3 (0.27 cases per 100,000 population). The increase in
      incidence was accompanied by a shift in age distribution, more cases being
      reported in adolescents and young adults: the median age increased to 15 years
      (range 2 months to 78 years). When assessed by age group, middle-school students
      (aged 12-17) had the highest incidence (6.57 per 100 000 population) and the
      highest proportion (31.4%). The N meningitidis serogroup was identified in 135
      (35.0%) of the cases of meningococcal disease; all were serogroup C. No cases due
      to serogroup A or other strains were found during the study period. The mean case
      fatality rate was 7.3%, with a peak of 16.9% in children younger than 6. Since
      winter 2003, a vaccination campaign has been partially implemented, but the
      effectiveness has been limited. CONCLUSIONS: The incidence of meningococcal
      disease has substantially increased in Hefei City, which may be due to the
      replacement of serogroup A by serogroup C. A shift in age distribution of cases
      to adolescents and young adults was found.

PMID- 18322130
TI  - Surgical adverse outcomes and patients' evaluation of quality of care: inherent
      risk or reduced quality of care?
AB  - BACKGROUND: Previous research has shown that sicker patients are less satisfied
      with their healthcare, but specific effects of adverse health outcomes have not
      been investigated. The present study aimed to assess whether patients who
      experience adverse outcomes, in hospital or after discharge, differ in their
      evaluation of quality of care compared with patients without adverse outcomes.
      METHOD: In-hospital adverse outcomes were prospectively recorded by surgeons and
      surgical residents as part of routine care. Four weeks after discharge, patients
      were interviewed by telephone about the occurrence of post-discharge adverse
      outcomes, and their overall evaluation of quality of hospital care and specific
      suggestions for improvements in the healthcare provided. RESULTS: Of 2145
      surgical patients admitted to the Leiden University Medical Center in 2003, 1876
      (88%) agreed to be interviewed. Overall evaluation was less favourable by
      patients who experienced post-discharge adverse outcomes only (average 19%
      lower). These patients were also more often dissatisfied (OR 2.02, 95% CI 1.24 to
      3.31) than patients without adverse outcomes, and they more often suggested that
      improvements were needed in medical care (OR 2.07, 1.45 to 2.95) and that
      patients were discharged too early (OR 3.26, 1.72 to 6.20). The effect of in
      hospital adverse outcomes alone was not statistically significant. Patients with
      both in-hospital and post-discharge adverse outcomes also found the quality of
      care to be lower (on average 33% lower) than patients without adverse outcomes.
      CONCLUSIONS: Post-discharge adverse outcomes negatively influence patients'
      overall evaluation of quality of care and are perceived as being discharged too
      early, suggesting that patients need better information at discharge.

PMID- 18322131
TI  - Super conus-collateral.

PMID- 18322132
TI  - Simultaneous presentation of coronary heart disease in identical twins.
AB  - The development of coronary artery disease involves a complex interplay between
      environmental and genetic factors, with premature coronary artery disease having
      a strong genetic component. We present the case a pair of monozygotic identical
      twins presenting near simultaneously with coronary artery disease and identical
      atherosclerotic lesions despite significant differences in environmental risk
      factors and being divided geographically by 12,000 miles. This is of enormous
      importance and not merely curiosity value as it will have implications for the
      prevention of coronary artery disease, provide an opportunity for the development
      of new therapeutic strategies, and aid targeted primary prevention through family
      screening.

PMID- 18322133
TI  - The cultural context of visual hallucinations.
AB  - Visual hallucinations (VH) are a cardinal neuropsychiatric symptom and often have
      important diagnostic implications. The interpretation of VH is influenced by the
      patient's social and cultural milieu, but the impact of socio-cultural factors on
      the interpretation, presentation and detection of VH has been little studied.
      When patients exhibit VH and other neuropsychiatric phenomena, appropriate
      sensitivity to the role of cultural factors is an important determinant of the
      success of the medical consultation. We discuss this issue using three
      illustrative cases.

PMID- 18322134
TI  - Antibiotic-resistant Campylobacter: an increasing problem.
AB  - The case is described of a 27-year-old woman who presented with an acute
      diarrhoeal illness. She was initially poorly responsive to antibiotics and
      developed lymphocytic ascites. Diagnosis was difficult to establish, and
      peritoneal tuberculosis was considered to be the most likely cause of her
      symptoms. Serological tests eventually confirmed Campylobacter jejuni infection.
      Campylobacter is one of the most common bacterial diarrhoeal infections, and
      complications, except for colitis, are rare except in specific disease states-
      for example, patients with cirrhosis or undergoing peritoneal dialysis.
      Antibiotic resistance is an increasing problem, and this may potentially lead to
      a greater incidence of complications in the future.

PMID- 18322135
TI  - Inpatient use and usefulness of a district general hospital neurologist.

PMID- 18322136
TI  - Factors influencing surgery as a choice of career: results of an electronic
      survey of early years surgical trainees.

PMID- 18322138
TI  - Induced TRPC1 expression increases protein phosphatase 2A sensitizing intestinal
      epithelial cells to apoptosis through inhibition of NF-kappaB activation.
AB  - Transient receptor potential canonical-1 (TRPC1) functions as a store-operated
      Ca2+ channel in intestinal epithelial cells (IECs), and induced TRPC1 expression
      sensitizes IECs to apoptosis by inhibiting NF-kappaB activation. However, the
      exact mechanism by which increased TRPC1 results in NF-kappaB inactivation
      remains elusive. Protein phosphatase 2A (PP2A) is a widely conserved protein
      serine/threonine phosphatase that is implicated in the regulation of a wide array
      of cellular functions including apoptosis. The present study tests the hypothesis
      that induced TRPC1 expression inhibits NF-kappaB activation by increasing PP2A
      activity through Ca2+ influx in IECs. The expression of TRPC1 induced by stable
      transfection with the wild-type TRPC1 gene increased PP2A activity as indicated
      by increases in levels of PP2A proteins and their phosphatase activity. Increased
      levels of PP2A activity in stable TRPC1-transfected IEC-6 cells (IEC-TRPC1) were
      associated with decreased nuclear levels of NF-kappaB proteins and a reduction in
      NF-kappaB-dependent transcriptional activity, although there were no changes in
      total NF-kappaB protein levels. Inhibition of PP2A activity by treatment with
      okadaic acid or PP2A silencing with small interfering RNA not only enhanced NF
      kappaB transactivation but also prevented the increased susceptibility of IEC
      TRPC1 cells to apoptosis induced by treatment with tumor necrosis factor-alpha
      (TNF-alpha)/cycloheximide (CHX). Decreasing Ca2+ influx by exposure to the Ca2+
      free medium reduced PP2A mRNA levels, destabilized PP2A proteins, and induced NF
      kappaB activation, thus blocking the increased sensitivity of IEC-TRPC1 cells to
      TNF-alpha/CHX-induced apoptosis. These results indicate that induced TRPC1
      expression increases PP2A activity through Ca2+ influx and that increased PP2A
      sensitizes IECs to apoptosis as a result of NF-kappaB inactivation.

PMID- 18322139
TI  - Calmodulin in adult mammalian skeletal muscle: localization and effect on
      sarcoplasmic reticulum Ca2+ release.
AB  - Calmodulin is a ubiquitous Ca2+ binding protein that binds to ryanodine rectors
      (RyR) and is thought to modulate its activity. Here we evaluated the effects of
      recombinant calmodulin on the rate of occurrence and spatial properties of Ca2+
      sparks as an assay of activation in saponin-permeabilized mouse myofibers.
      Control myofibers exhibited a time-dependent increase and subsequent decrease in
      spark frequency. Recombinant wild-type calmodulin prevented the time-dependent
      appearance of Ca2+ sparks and decreased the derived Ca2+ flux from the
      sarcoplasmic reticulum during a spark by approximately 37%. A recombinant Ca2+
      insensitive form of calmodulin resulted in an instantaneous increase in spark
      frequency as well as an increase in the derived Ca2+ flux by approximately 24%.
      Endogenous calmodulin was found to primarily localize to the Z-line.
      Surprisingly, removal of endogenous calmodulin did not alter the time dependence
      of Ca2+ spark appearance. These results indicate that calmodulin may not be
      essential for RyR1-dependent Ca2+ release in adult mammalian skeletal muscle.

PMID- 18322140
TI  - Carbonic anhydrase 2-like a and 15a are involved in acid-base regulation and Na+
      uptake in zebrafish H+-ATPase-rich cells.
AB  - H(+)-ATPase-rich (HR) cells in zebrafish gills/skin were found to carry out Na+
      uptake and acid-base regulation through a mechanism similar to that which occurs
      in mammalian proximal tubular cells. However, the roles of carbonic anhydrases
      (CAs) in this mechanism in zebrafish HR cells are still unclear. The present
      study used a functional genomic approach to identify 20 CA isoforms in zebrafish.
      By screening with whole mount in situ hybridization, only zca2-like a and zca15a
      were found to be expressed in specific groups of cells in zebrafish gills/skin,
      and further analyses by triple in situ hybridization and immunocytochemistry
      demonstrated specific colocalizations of the two zca isoforms in HR cells.
      Knockdown of zca2-like a caused no change in and knockdown of zca15a caused an
      increase in H+ activity at the apical surface of HR cells at 24 h
      postfertilization (hpf). Later, at 96 hpf, both the zca2-like a and zca15a
      morphants showed decreased H+ activity and increased Na+ uptake, with concomitant
      upregulation of znhe3b and downregulation of zatp6v1a (H+-ATPase A-subunit)
      expressions. Acclimation to both acidic and low-Na+ fresh water caused
      upregulation of zca15a expression but did not change the zca2-like a mRNA level
      in zebrafish gills. These results provide molecular physiological evidence to
      support the roles of these two zCA isoforms in Na+ uptake and acid-base
      regulation mechanisms in zebrafish HR cells.

PMID- 18322141
TI  - Molecular mechanisms of epithelial cell-specific expression and regulation of the
      human anion exchanger (pendrin) gene.
AB  - Pendrin, a Cl(-)/anion exchanger encoded by the gene PDS, is highly expressed in
      the kidney, thyroid, and inner ear epithelia and is essential for bicarbonate
      secretion, iodide accumulation, and endolymph ion balance, respectively. This
      study aimed to define promoter regulatory elements essential for renal, thyroid,
      and inner ear epithelial cell-specific expression of human PDS (hPDS) and to
      explore the effect of ambient pH and aldosterone on hPDS promoter activity.
      Endogenous pendrin mRNA and protein were detected in renal HEK293, thyroid LA2,
      and inner ear VOT36 epithelial cell lines, but not in the fibroblast cell line,
      NIH3T3. A 4.2-kb hPDS 5'-flanking DNA sequence and consecutive 5'-deletion
      products were cloned into luciferase reporter vectors and transiently transfected
      into the above cell lines. Distinct differences in expression/activity of deduced
      positive/negative regulatory elements within the hPDS promoter between HEK293,
      LA2, and VOT36 cells were demonstrated, with only basal activity in NIH3T3 cells.
      Acidic pH (7.0-7.1) decreased and alkaline pH (7.6-7.7) increased hPDS promoter
      activity in transfected HEK293 and VOT36, but not in LA2 cells. Aldosterone (10(
      8) M) reduced hPDS promoter activity in HEK293 but had no effect in LA2 and VOT36
      cells. These pH and aldosterone-induced effects on the hPDS promoter occurred
      within 96-bp and 89-bp regions, respectively, which likely contain distinct
      response elements to these modulators. Acidic pH and aldosterone decreased, and
      alkaline pH increased, endogenous pendrin mRNA level in HEK293 cells. In
      conclusion, pendrin-mediated HCO3(-) secretion in the renal tubule and anion
      transport in the endolymph may be regulated transcriptionally by systemic pH and
      aldosterone.

PMID- 18322142
TI  - H9c2 cardiomyoblasts produce thyroid hormone.
AB  - Thyroid hormone acts on a wide range of tissues. In the cardiovascular system,
      thyroid hormone is an important regulator of cardiac function and cardiovascular
      hemodynamics. Although some early reports in the literature suggested an unknown
      extrathyroidal source of thyroid hormone, it is currently thought to be produced
      exclusively in the thyroid gland, a highly specialized organ with the sole
      function of generating, storing, and secreting thyroid hormone. Whereas most of
      the proteins necessary for thyroid hormone synthesis are thought to be expressed
      exclusively in the thyroid gland, we now have found evidence that all of these
      proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter,
      pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also
      expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be
      transiently upregulated in an in vitro model of ischemia. When performing these
      experiments in the presence of 125 I, we found that 125 I was integrated into
      thyroglobulin and that under ischemia-like conditions the radioactive signal in
      thyroglobulin was reduced. Concomitantly we observed an increase of
      intracellularly produced, 125 I-labeled thyroid hormone. In conclusion, our
      findings demonstrate for the first time that cardiomyocytes produce thyroid
      hormone in a manner adapted to the cell's environment.

PMID- 18322143
TI  - Screening and surveillance for the early detection of colorectal cancer and
      adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the
      US Multi-Society Task Force on Colorectal Cancer, and the American College of
      Radiology.
AB  - In the United States, colorectal cancer (CRC) is the third most common cancer
      diagnosed among men and women and the second leading cause of death from cancer.
      CRC largely can be prevented by the detection and removal of adenomatous polyps,
      and survival is significantly better when CRC is diagnosed while still localized.
      In 2006 to 2007, the American Cancer Society, the US Multi Society Task Force on
      Colorectal Cancer, and the American College of Radiology came together to develop
      consensus guidelines for the detection of adenomatous polyps and CRC in
      asymptomatic average-risk adults. In this update of each organization's
      guidelines, screening tests are grouped into those that primarily detect cancer
      early and those that can detect cancer early and also can detect adenomatous
      polyps, thus providing a greater potential for prevention through polypectomy.
      When possible, clinicians should make patients aware of the full range of
      screening options, but at a minimum they should be prepared to offer patients a
      choice between a screening test that is effective at both early cancer detection
      and cancer prevention through the detection and removal of polyps and a screening
      test that primarily is effective at early cancer detection. It is the strong
      opinion of these 3 organizations that colon cancer prevention should be the
      primary goal of screening.

PMID- 18322144
TI  - Ammonia triggers photodamage of photosystem II in the cyanobacterium
      Synechocystis sp. strain PCC 6803.
AB  - Ammonia has long been known to be toxic for many photosynthetic organisms;
      however, the target for its toxicity remains elusive. Here, we show that in the
      cyanobacterium Synechocystis sp. strain PCC 6803, ammonia triggers a rapid
      photodamage of photosystem II (PSII). Whereas wild-type cells can cope with this
      damage by turning on the FtsH2-dependent PSII repair cycle, the FtsH2-deficient
      mutant is highly sensitive and loses PSII activity at millimolar concentration of
      ammonia. Ammonia-triggered PSII destruction is light dependent and occurs already
      at low photon fluence rates. Experiments with monochromatic light showed that
      ammonia-promoted PSII photoinhibition is executed by wavebands known to directly
      destroy the manganese cluster in the PSII oxygen-evolving complex, suggesting
      that the oxygen-evolving complex may be a direct target for ammonia toxicity.

PMID- 18322145
TI  - Expression analysis of genes associated with the induction of the carbon
      concentrating mechanism in Chlamydomonas reinhardtii.
AB  - Acclimation to varying CO2 concentrations and light intensities is associated
      with the monitoring of environmental changes by controlling genetic and
      physiological responses through CO2 and light signal transduction. While CO2 and
      light signals are indispensable for photosynthesis, and these environmental
      factors have been proposed as strongly associated with each other, studies
      linking these components are largely limited to work on higher plants. In this
      study, we examined the physiological characteristics of a green alga,
      Chlamydomonas reinhardtii, exposed to various light intensities or CO2
      concentrations. Acclimation to CO2-limiting conditions by Chlamydomonas requires
      the induction of a carbon-concentrating mechanism (CCM) to allow the uptake of
      inorganic carbon (Ci) and increase the affinity for Ci. We revealed that the
      induction of the CCM is not solely dependent on absolute environmental Ci
      concentrations but is also affected by light intensity. Using a cDNA array
      containing 10,368 expressed sequence tags, we also obtained global expression
      profiles related to the physiological responses. The induction of several CCM
      associated genes was strongly affected by high light as well as CO2
      concentrations. We identified novel candidates for Ci transporters and CO2
      responsive regulatory factors whose expression levels were significantly
      increased during the induction of the CCM.

PMID- 18322147
TI  - Assessment of nerve stimulation-induced release of purines from mouse kidneys by
      tandem mass spectrometry.
AB  - Adenosine, formed from AMP and metabolized to inosine, modulates renal
      sympathetic neurotransmission. The present study had two goals: 1) to develop
      ultrasensitive and specific mass spectrometry-based assays for cAMP, AMP,
      adenosine, inosine, and, for comparison, guanosine using state-of-the-art tandem
      liquid chromatography-mass spectrometry (LC-MS-MS); and 2) to quantify the
      effects of renal sympathetic nerve stimulation on the release of cAMP, AMP,
      adenosine, inosine, and guanosine from the isolated, perfused mouse kidney. Using
      LC-MS-MS, we developed highly sensitive (detection limit of 0.02-0.05 pg/microl)
      and accurate (r(2) > 0.99) assays for all the aforementioned compounds. In the
      perfused mouse kidney (n = 9), periarterial (renal sympathetic) nerve stimulation
      elicited a frequency-dependent (0, 3, 5, 7, and 9 Hz) and significant (p =
      0.0148, repeated measures analysis of variance) increase in the concentration of
      inosine in the renal venous perfusate (29 +/- 8, 51 +/- 8, 54 +/- 11, 65 +/- 15,
      and 80 +/- 20 pg/microl, respectively), yet concomitantly decreased (p = 0.0239,
      repeated measures analysis of variance) the concentration of AMP in the renal
      venous perfusate (3.8 +/- 1.3, 3.2 +/- 1.7, 2.4 +/- 1.5, 2.0 +/- 1.1, and 1.1 +/-
      0.4 pg/microl, respectively). No significant changes were observed in the levels
      of adenosine, cAMP, or guanosine in the renal venous perfusate. These results
      indicate that using state-of-the-art mass spectrometric methods, it is possible
      to investigate trace amounts of purines released from mouse organs in perfusion
      and that renal sympathetic nerve stimulation is associated with a robust increase
      in the main metabolite of adenosine (inosine), while concomitantly decreasing
      AMP. This suggests that renal sympathetic nerve stimulation influences the
      efficiency of AMP conversion to adenosine and hence to inosine.

PMID- 18322146
TI  - Arabidopsis ribosomal proteins RPL23aA and RPL23aB are differentially targeted to
      the nucleolus and are disparately required for normal development.
AB  - Protein synthesis is catalyzed by the ribosome, a two-subunit enzyme comprised of
      four ribosomal RNAs and, in Arabidopsis (Arabidopsis thaliana), 81 ribosomal
      proteins (r-proteins). Plant r-protein genes exist as families of multiple
      expressed members, yet only one r-protein from each family is incorporated into
      any given ribosome, suggesting that many r-protein genes may be functionally
      redundant or development/tissue/stress specific. Here, we characterized the
      localization and gene-silencing phenotypes of a large subunit r-protein family,
      RPL23a, containing two expressed genes (RPL23aA and RPL23aB). Live cell imaging
      of RPL23aA and RPL23aB in tobacco with a C-terminal fluorescent-protein tag
      demonstrated that both isoforms accumulated in the nucleolus; however, only
      RPL23aA was targeted to the nucleolus with an N-terminal fluorescent protein tag,
      suggesting divergence in targeting efficiency of localization signals.
      Independent knockdowns of endogenous RPL23aA and RPL23aB transcript levels using
      RNA interference determined that an RPL23aB knockdown did not alter plant growth
      or development. Conversely, a knockdown of RPL23aA produced a pleiotropic
      phenotype characterized by growth retardation, irregular leaf and root
      morphology, abnormal phyllotaxy and vasculature, and loss of apical dominance.
      Comparison to other mutants suggests that the phenotype results from reduced
      ribosome biogenesis, and we postulate a link between biogenesis, microRNA-target
      degradation, and maintenance of auxin homeostasis. An additional RNA interference
      construct that coordinately silenced both RPL23aA and RPL23aB demonstrated that
      this family is essential for viability.

PMID- 18322148
TI  - Antitorsadogenic effects of ({+/-})-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2
      methoxyphenoxy)propyl]-1-piperazine (ranolazine) in anesthetized rabbits.
AB  - Ranolazine [Ranexa; (+/-)-N-(2,6-dimethyl-phenyl)-(4[2-hydroxy-3-(2
      methoxyphenoxy)propyl]-1-piperazine] is novel anti-ischemic agent that has been
      shown to inhibit late I(Na) and I(Kr) and to have antiarrhythmic effects in
      various preclinical in vitro models. This study was undertaken to investigate the
      effects of ranolazine on drug-induced Torsade de Pointes (TdP) in vivo. TdP was
      induced by an I(Kr) blocker, clofilium, in anesthetized, alpha(1)-agonist
      sensitized rabbits. Clofilium prolonged QT interval corrected for heart rate
      (QTc) (52 +/- 9%) and monophasic action potential duration (MAPD)(90) (56 +/- 9%)
      and caused TdP in eight of eight rabbits. Pretreatment with ranolazine (480
      microg/kg/min) or lidocaine (200 microg/kg/min) reduced the clofilium-induced
      prolongation of QTc (15 +/- 3 and 19 +/- 3%, respectively, p < 0.001 versus
      vehicle) and MAPD(90) (21 +/- 4 and 20 +/- 2%, respectively, p < 0.001 versus
      vehicle) and prevented the occurrence of TdP (zero of eight and zero of eight,
      respectively). Administration of ranolazine after the first episode of TdP
      terminated TdP and prevented its recurrence (zero of four versus vehicle, four of
      four). To rule out an alpha(1)-adrenoceptor antagonistic activity of ranolazine,
      we compared the effects of ranolazine on blood pressure with those of the
      alpha(1)-antagonist, prazosin. Although prazosin (10 microg/kg/min) markedly
      shifted the phenylephrine (alpha(1)-agonist) dose-response curve to the right, it
      did not have any effect on clofilium-induced prolongation of QTc and MAPD(90) (43
      +/- 7 and 53 +/- 9%, respectively) or the occurrence of TdP (seven of eight). In
      contrast, ranolazine completely suppressed TdP but did not cause any shift in the
      phenylephrine dose-response curve at the highest dose tested (480 microg/kg/min).
      We conclude that ranolazine antagonizes the ventricular repolarization changes
      caused by clofilium and suppresses clofilium-induced TdP in rabbits.

PMID- 18322149
TI  - Differential effect of the protein synthesis inhibitors puromycin and
      cycloheximide on vascular smooth muscle cell viability.
AB  - Recent evidence indicates that the protein synthesis inhibitor cycloheximide
      triggers selective macrophage death in rabbit atheroma-like lesions without
      affecting smooth muscle cells (SMCs) or the endothelium, thereby favoring a
      stable plaque phenotype. In this study, we report that puromycin, a protein
      synthesis inhibitor with a different mode of action but with similar ability to
      inhibit de novo protein synthesis, did not reveal plaque-stabilizing effects. The
      macrophage and the SMC content readily decreased in puromycin-treated atheroma
      like lesions in rabbit carotid arteries. Moreover, puromycin induced apoptosis in
      macrophages and SMCs in vitro. Puromycin-treated SMCs showed signs of endoplasmic
      reticulum (ER) stress, as demonstrated by CCAAT/enhancer-binding protein
      homologous protein (CHOP) protein expression, splicing of X-box-binding protein 1
      mRNA, and phosphorylation of eukaryotic translation initiation factor 2alpha. The
      ER stress inducer thapsigargin up-regulated CHOP protein expression in SMCs
      without affecting their viability, indicating that ER stress not necessarily
      results in cell death. Puromycin, but not thapsigargin, activated the ER stress
      related caspase-12. Treatment of SMCs with a combination of cycloheximide and
      puromycin inhibited ER stress and partially improved SMC viability. In addition,
      puromycin, but not cycloheximide or thapsigargin, induced intracellular
      accumulation of polyubiquitinated proteins in SMCs, whereas the proteasome
      function was not affected. Taken together, puromycin, in contrast to
      cycloheximide, induces SMC apoptosis, thereby favoring an unstable plaque
      phenotype. SMC death upon puromycin treatment could only be partially prevented
      by cycloheximide, which completely blocked ER stress. However, other or
      additional mechanisms, such as increased polyubiquitination of proteins, might be
      involved in puromycin-induced SMC death.

PMID- 18322150
TI  - Pharmacological assessment of m1 muscarinic acetylcholine receptor-gq/11 protein
      coupling in membranes prepared from postmortem human brain tissue.
AB  - Using a selective Galpha(q/11) protein antibody capture guanosine 5'-O-(3
      [35S]thio)triphosphate ([35S]GTPgammaS) binding approach, it has been possible to
      perform a quantitative pharmacological examination of the functional activity of
      the M(1) muscarinic acetylcholine receptor (mAChR) in membranes prepared from
      human postmortem cerebral cortex. Oxotremorine-M caused a > or = 2-fold increase
      in [35S]GTPgammaS-Galpha(q/11) binding with a pEC(50) of 6.06 +/- 0.16 in
      Brodmann's areas 23 and 25 that was almost completely inhibited by preincubation
      of membranes with the M(1) mAChR subtype-selective antagonist muscarinic toxin-7.
      In addition, the orthosteric and allosteric agonists, xanomeline [3(3-hexyloxy
      1,2,5-thiadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyridine] and AC-42 (4-n-butyl
      1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine hydrogen chloride), increased
      [35S]-GTPgammaS-Galpha(q/11) binding, but with reduced intrinsic activities,
      inducing maximal responses that were 42 +/- 1 and 44 +/- 2% of the oxotremorine-M
      induced response, respectively. These data indicate that the M(1) receptor is the
      predominant mAChR subtype coupling to the Galpha(q/11) G protein in these brain
      regions and that it is possible to quantify the potency and intrinsic activity of
      full and partial M(1) mAChR receptor agonists in postmortem human brain using a
      selective Galpha(q/11) protein antibody capture [35S]GTPgammaS binding assay.

PMID- 18322151
TI  - The impact of orthosteric radioligand depletion on the quantification of
      allosteric modulator interactions.
AB  - Radioligand binding assays remain a common method for quantifying the effects of
      allosteric modulators at G protein-coupled receptors. The allosteric ternary
      complex model (ATCM) is the simplest model applied to derive estimates of
      modulator affinity (K(B)) and cooperativity (alpha), which are necessary for
      understanding structure-activity relationships. However, the increasing drive
      toward assay miniaturization in modern drug discovery may lead to conditions
      where appreciable ligand depletion occurs in the assay. Theoretical simulations
      investigating the impact of orthosteric radioligand depletion on the estimation
      of ATCM parameters revealed the following. 1) For allosteric inhibitors,
      application of the standard ATCM to data obtained under depletion conditions
      leads to an underestimation of pK(B) and an overestimation of log alpha. 2) For
      allosteric enhancers, the opposite was noted, but not always; the nonlinear
      regression algorithm is more likely to struggle to converge to a satisfactory
      solution of (nondepletion) ATCM parameters in this situation. 3) Application of a
      novel ATCM that explicitly incorporates orthosteric ligand depletion will yield
      more reliable model estimates, provided the degree of depletion is not high (<
      approximately 50%). Subsequent experiments investigated the interaction between
      [3H]N-methylscopolamine and the allosteric enhancer, alcuronium, or inhibitor,
      gallamine, in the presence of increasing concentrations of M(2) muscarinic
      acetylcholine receptor and showed that application of an ATCM that explicitly
      incorporates radioligand depletion can indeed give more robust estimates of
      modulator affinity and cooperativity estimates than the standard model. These
      results have important implications for the quantification of allosteric
      modulator actions in binding-based discovery assays.

PMID- 18322152
TI  - A serotonergic system in veins: serotonin transporter-independent uptake.
AB  - We hypothesized that the 5-hydroxytryptamine (5-HT; serotonin) system is present
      and functional in veins. In vena cava (VC), the presence of the 5-HT synthesis
      rate-limiting enzyme tryptophan hydroxylase-1 mRNA and accumulation of the 5-HT
      synthesis intermediate 5-hydroxytryptophan after incubation with tryptophan
      supported the ability of veins to synthesize 5-HT. The presence of 5-HT and its
      metabolite 5-hydroxyindole acetic acid was measured by high-performance liquid
      chromatography in VC and jugular vein (JV), and it was compared with similarly
      sized arteries aorta (RA) and carotid (CA), respectively. In rats treated with
      the monoamine oxidase-A (MAO-A) inhibitor pargyline to prevent 5-HT metabolism,
      basal 5-HT levels were higher in veins than in arteries. 5-HT uptake was observed
      after exposure to exogenous 5-HT in all vessels. The presence of MAO-A and the 5
      HT transporter (SERT) in VC was observed by immunohistochemistry and Western
      analysis. However, 5-HT uptake was not inhibited by the SERT inhibitors
      fluoxetine and/or fluvoxamine in VC and JV, as opposed to the inhibition in RA
      and CA. Moreover, studies performed in VC from mutant rats lacking SERT showed no
      differences in 5-HT uptake compared with VC from wild type. These data suggest
      the SERT is not functional under physiological conditions in veins. The
      differences in 5-HT handling between veins and arteries may represent alternative
      avenues for targeting the 5-HT system in the peripheral circulation for
      controlling vascular tone.

PMID- 18322153
TI  - The effects of imatinib on pregnancy outcome.
AB  - Imatinib has now been in use for almost 10 years. Despite this cumulative
      experience, little is known about its effects on pregnancy; as a result, there
      are few published data to facilitate the counseling of women who conceive while
      taking imatinib. The results we now present provide information which may be of
      use in such circumstances. Of 180 women exposed to imatinib during pregnancy,
      outcome data are available for 125 (69%). Of those with known outcomes, 50%
      delivered normal infants and 28% underwent elective terminations, 3 following the
      identification of abnormalities. There were a total of 12 infants in whom
      abnormalities were identified, 3 of which had strikingly similar complex
      malformations that are clearly a cause for concern. It appears that although most
      pregnancies exposed to imatinib are likely to have a successful outcome, there
      remains a risk that exposure may result in serious fetal malformations.

PMID- 18322154
TI  - Integrins and matrix in the glomerulus: old mysteries and new insights.

PMID- 18322155
TI  - Are podocytes passive or provocative in proteinuric glomerular pathology?

PMID- 18322156
TI  - What does a serum sodium cost?

PMID- 18322157
TI  - A national course for renal fellows: the origins of renal physiology.

PMID- 18322158
TI  - Use of cardiac biomarkers in end-stage renal disease.
AB  - Mortality among patients with ESRD remains high because of an excessive
      cardiovascular risk related to a very high incidence of cardiac hypertrophy,
      cardiomyopathy, heart failure, and coronary artery disease. Identifying serum
      biomarkers that are useful in profiling cardiovascular risk and enabling
      stratification of early mortality and cardiovascular risk is an important goal in
      the treatment of these patients. This review examines current evidence pertaining
      to the role and utility of two emerging cardiac biomarkers, B-type natriuretic
      peptide and cardiac troponin T, in patients with ESRD. Together, these data
      demonstrate how these two cardiac biomarkers may play an adjunctive role to
      echocardiography in assessing cardiovascular risk and how they may aid in the
      clinical treatment of these patients.

PMID- 18322159
TI  - The secret of immortal time bias in epidemiologic studies.

PMID- 18322160
TI  - Bicarbonate therapy in severe metabolic acidosis.
AB  - The utility of bicarbonate administration to patients with severe metabolic
      acidosis remains controversial. Chronic bicarbonate replacement is obviously
      indicated for patients who continue to lose bicarbonate in the ambulatory
      setting, particularly patients with renal tubular acidosis syndromes or diarrhea.
      In patients with acute lactic acidosis and ketoacidosis, lactate and ketone
      bodies can be converted back to bicarbonate if the clinical situation improves.
      For these patients, therapy must be individualized. In general, bicarbonate
      should be given at an arterial blood pH of < or =7.0. The amount given should be
      what is calculated to bring the pH up to 7.2. The urge to give bicarbonate to a
      patient with severe acidemia is apt to be all but irresistible. Intervention
      should be restrained, however, unless the clinical situation clearly suggests
      benefit. Here we discuss the pros and cons of bicarbonate therapy for patients
      with severe metabolic acidosis.

PMID- 18322161
TI  - Glomerulotubular balance, tubuloglomerular feedback, and salt homeostasis.
AB  - The homeostasis of NaCl is critical to complex organisms with closed blood
      systems. Kidneys regulate this salt excretion by modulating the rapport between
      glomeruli and tubules. The tubules respond to glomeruli with glomerulotubular
      balance, whereas glomeruli respond to tubules through tubuloglomerular feedback.
      These relationships are dynamic, mysterious, and amenable to mathematical
      analyses. The biology underlining what is known about these interactions is
      observational, fragmentary, and somewhat inconclusive. Discussed here is a simple
      tethering of these interrelated concepts.

PMID- 18322162
TI  - Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones.
AB  - Most kidney stones are composed primarily of calcium oxalate. Oxalobacter
      formigenes is a Gram-negative, anaerobic bacterium that metabolizes oxalate in
      the intestinal tract and is present in a large proportion of the normal adult
      population. It was hypothesized that the absence of O. formigenes could lead to
      increased colonic absorption of oxalate, and the subsequent increase in urinary
      oxalate could favor the development of stones. To test this hypothesis, a case
      control study involving 247 adult patients with recurrent calcium oxalate stones
      and 259 age-, gender-, and region-matched control subjects was performed. The
      prevalence of O. formigenes, determined by stool culture, was 17% among case
      patients and 38% among control subjects; on the basis of multivariate analysis
      controlling demographic factors, dietary oxalate, and antibiotic use, the odds
      ratio for colonization was 0.3 (95% confidence interval 0.2 to 0.5). The inverse
      association was consistently present within strata of age, gender,
      race/ethnicity, region, and antibiotic use. Among the subset of participants who
      completed a 24-h urine collection, the risk for kidney stones was directly
      proportional to urinary oxalate, but when urinary factors were included in the
      multivariable model, the odds ratio for O. formigenes remained 0.3 (95%
      confidence interval 0.1 to 0.7). Surprisingly, median urinary oxalate excretion
      did not differ with the presence or absence of O. formigenes colonization. In
      conclusion, these results suggest that colonization with O. formigenes is
      associated with a 70% reduction in the risk for being a recurrent calcium oxalate
      stone former.

PMID- 18322163
TI  - Epigenetic regulation of BMP7 in the regenerative response to ischemia.
AB  - Kidneys damaged by ischemia have the potential to regenerate through a mechanism
      involving intrarenal induction of protective factors, including bone
      morphogenetic protein-7 (BMP7). Epigenetic changes, such as alterations in
      histone modifications, have also been shown to play a role in various pathologic
      conditions, but their involvement in ischemic injury and regeneration remains
      unknown. This study investigated whether changes in histone acetylation,
      regulated by histone acetyltransferase and histone deacetylase (HDAC), are
      induced by renal ischemia and involved in the regenerative response.
      Ischemia/reperfusion of the mouse kidney induced a transient decrease in histone
      acetylation in proximal tubular cells, likely as a result of a decrease in
      histone acetyltransferase activity as suggested by experiments with energy
      depleted renal epithelial cells in culture. During recovery after transient
      energy depletion in epithelial cells, the HDAC isozyme HDAC5 was selectively
      downregulated in parallel with the return of acetylated histone. Knockdown of
      HDAC5 by RNAi significantly increased histone acetylation and BMP7 expression.
      BMP7 induction and HDAC5 downregulation in the recovery phase were also observed
      in proximal tubular cells in vivo after transient ischemia. These data indicate
      that ischemia induces dynamic epigenetic changes involving HDAC5 downregulation,
      which contributes to histone re-acetylation and BMP7 induction in the recovery
      phase. This highlights HDAC5 as a modulator of the regenerative response after
      ischemia and suggests HDAC5 inhibition may be a therapeutic strategy to enhance
      BMP7 expression.

PMID- 18322164
TI  - Vesicoureteral reflux.
AB  - Vesicoureteral reflux (VUR), the retrograde flow of urine from the bladder toward
      the kidney, is common in young children. About 30% of children with urinary tract
      infections will be diagnosed with VUR after a voiding cystourethrogram. For most,
      VUR will resolve spontaneously; 20% to 30% will have further infections, but few
      will experience long-term renal sequelae. Developmentally, VUR arises from
      disruption of complex signaling pathways and cellular differentiation. These
      mechanisms are probably genetically programmed but may be influenced by
      environmental exposures. Phenotypic expression of VUR is variable, ranging from
      asymptomatic forms to severe renal parenchymal disease and end-stage disease. VUR
      is often familial but is genetically heterogeneous with variability in mode of
      inheritance and in which gene, or the number of genes, that are involved.
      Numerous genetic studies that explore associations with VUR are available. The
      relative utility of these for understanding the genetics of VUR is often limited
      because of small sample size, poor methodology, and a diverse spectrum of
      patients. Much, if not all, of the renal parenchymal damage associated with end
      stage disease is likely to be congenital, which limits the opportunity for
      intervention to familial cases where risk prediction may be available. Management
      of children with VUR remains controversial because there is no strong supportive
      evidence that prophylactic antibiotics or surgical intervention improve outcomes.
      Furthermore, well-designed genetic epidemiological studies focusing on the severe
      end of the VUR phenotype may help define the causal pathway and identify
      modifiable or disease predictive factors.

PMID- 18322165
TI  - Comment on "MHC class II expression identifies functionally distinct human
      regulatory T cells".

PMID- 18322166
TI  - NKT cells in tumor immunity: opposing subsets define a new immunoregulatory axis.
AB  - NKT cells are true Ag-specific T cells that also have innate properties and form
      a bridge between the innate and adaptive immune systems. Distinct NKT cell
      subsets play positive and negative regulatory roles and define a new
      immunoregulatory axis with broad implications for tumor immunity and other
      immunological and disease settings.

PMID- 18322167
TI  - Cutting edge: programmed death-1 expression is increased on immunocytes in
      chronic hepatitis C virus and predicts failure of response to antiviral therapy:
      race-dependent differences.
AB  - Up-regulation of programmed death-1 (PD-1) identifies exhausted T cells in
      various mouse and human viral models including chronic hepatitis C virus (HCV)
      infection, which is characterized by impaired CTL function. A large proportion of
      patients fail to eradicate HCV with current IFN-based antiviral therapy; in
      particular, African Americans are less likely to respond, but the mechanisms for
      these differences are not fully elucidated. In this study, in 72 treatment-naive
      patients with persistent HCV we found that PD-1 was significantly up-regulated on
      CD4(+) and CD8(+) T cells, HCV-specific CTLs, and NK cells. Increased PD-1 on HCV
      specific CTLs was significantly associated with failed early and sustained
      virologic response to therapy in African American but not Caucasian American
      patients. Patients with sustained virologic response showed decreases in PD-1 on
      total CD4(+) T cells, HCV-specific CTLs, and the CD56(bright) NK subset after
      therapy completion. Collectively, these data indicate that PD-1 is critical in
      persistent HCV and successful therapy results in global down-regulation of its
      expression.

PMID- 18322168
TI  - Cutting edge: langerin/CD207 receptor on dendritic cells mediates efficient
      antigen presentation on MHC I and II products in vivo.
AB  - The targeted delivery of Ags to dendritic cell (DCs) in vivo greatly improves the
      efficiency of Ag presentation to T cells and allows an analysis of receptor
      function. To evaluate the function of Langerin/CD207, a receptor expressed by
      subsets of DCs that frequently coexpress the DEC205/CD205 receptor, we
      genetically introduced OVA into the C terminus of anti-receptor Ab H chains.
      Taking advantage of the new L31 mAb to the extracellular domain of mouse
      Langerin, we find that the hybrid Ab targets appropriate DC subsets in draining
      lymph nodes and spleen. OVA is then presented efficiently to CD8(+) and CD4(+) T
      cells in vivo, which undergo 4-8 cycles of division in 3 days. Peptide MHC I and
      II complexes persist for days. Dose response studies indicate only modest
      differences between Langerin and DEC receptors in these functions. Thus, Langerin
      effectively mediates Ag presentation.

PMID- 18322169
TI  - Cutting edge: human CD4-CD8- thymocytes express FOXP3 in the absence of a TCR.
AB  - The best candidate for regulatory T (Treg) cell lineage-determining factor is
      currently the Forkhead box transcription factor FOXP3. FOXP3 up-regulation has
      been linked to TCR-mediated signals, and in mice the abrogation of TCR expression
      or signals also prevents FoxP3 expression. In contrast, the TCR dependence of
      human FOXP3 is assumed but not established. In this study we show on a single
      cell level that 1.4% (range 0.1-3.8%) of CD4(-)CD8(-) thymocytes in healthy
      humans express FOXP3, two thirds of them without any detectable alphabeta TCR.
      These TCR(-)FOXP3(+) cells were mostly CD25(-) and did not express gammadelta TCR
      or B cell, NK cell, or monocyte-associated markers. Like mature Treg cells, they
      were mostly CD2(+)CD127(low) and expressed cytoplasmic CTLA-4. Our results
      suggest that in immature human thymocytes the expression of FOXP3 precedes
      surface TCR, in which case TCR-mediated signals cannot be responsible for the
      thymic up-regulation of FOXP3.

PMID- 18322170
TI  - Cutting edge: the dependence of plasma cells and independence of memory B cells
      on BAFF and APRIL.
AB  - Memory B (B(MEM)) cells and long-lived bone marrow plasma cells (BM-PCs) persist
      within local environmental survival niches that afford cellular longevity.
      However, the factors supporting B(MEM) cell survival within the secondary
      lymphoid organs and allowing BM-PC persistence in the bone marrow remain poorly
      characterized. We report herein that long-lived B(MEM) cell survival and function
      are completely independent of BAFF (B cell-activating factor of the TNF family)
      or APRIL (a proliferation-inducing ligand). Thus, B(MEM) cells represent the only
      mature B2 lineage subset whose survival is independent of these ligands. We have
      previously shown that the TNFR family member receptor BCMA (B cell maturation Ag)
      is a critical survival receptor for BM-PC survival in vivo. We identify in this
      study the ligands critical for BM-PC survival and show that either BAFF or APRIL
      supports the survival of BM-PCs in vivo. These data define the BAFF/APRIL
      dependent and -independent components of long-lived humoral immunity.

PMID- 18322171
TI  - Estrogen receptor alpha, but not beta, is required for optimal dendritic cell
      differentiation and [corrected] CD40-induced cytokine production.
AB  - Dendritic cells (DC) are critical actors in the initiation of primary immune
      responses and regulation of self-tolerance. The steroid sex hormone 17beta
      estradiol (E(2)) has been shown to promote the differentiation of DCs from bone
      marrow (BM) precursors in vitro. However, the estrogen receptor (ER) involved in
      this effect has not yet been characterized. Using recently generated ERalpha- or
      ERbeta-deficient mice, we investigated the role of ER isotypes in DC
      differentiation and acquisition of effector functions. We report that estrogen
      dependent activation of ERalpha, but not ERbeta, is required for normal DC
      development from BM precursors cultured with GM-CSF. We show that reduced numbers
      of DCs were generated in the absence of ERalpha activation and provide evidence
      for a cell-autonomous function of ERalpha signaling in DC differentiation.
      ERalpha-deficient DCs were phenotypically and functionally distinct from wild
      type DCs generated in the presence of estrogens. In response to microbial
      components, ERalpha-deficient DCs failed to up-regulate MHC class II and CD86
      molecules, which could account for their reduced capacity to prime naive CD4(+) T
      lymphocytes. Although they retained the ability to express CD40 and to produce
      proinflammatory cytokines (e.g., IL-12, IL-6) upon TLR engagement, ERalpha
      deficient DCs were defective in their ability to secrete such cytokines in
      response to CD40-CD40L interactions. Taken together, these results provide the
      first genetic evidence that ERalpha is the main receptor regulating estrogen
      dependent DC differentiation in vitro and acquisition of their effector
      functions.

PMID- 18322172
TI  - Morphine withdrawal inhibits IL-12 induction in a macrophage cell line through a
      mechanism that involves cAMP.
AB  - There are very few studies that examine the effects that morphine withdrawal has
      on immune functioning, and of these even fewer describe the mechanisms by which
      withdrawal brings about these changes. Our previous work demonstrated that
      morphine withdrawal contributed to Th cell differentiation by biasing cells
      toward the Th2 lineage. A major finding from these studies was that IL-12 was
      decreased following withdrawal, and it was concluded that this decrease may be a
      mechanism by which morphine withdrawal is mediating Th2 polarization. Therefore,
      it was the aim of the current studies to develop an in vitro model to examine the
      process of morphine withdrawal and to understand the signaling mechanisms that
      withdrawal may use to effect IL-12 production through the use of this model. It
      was demonstrated and concluded that morphine withdrawal may be effecting IL-12
      production by increasing cAMP levels, which activates protein kinase A. Protein
      kinase A activation then prevents the phosphorylation and subsequent degradation
      of IkappaB, which in turn prevents translocation of the NF-kappaB p65 subunit to
      the nucleus to transactivate the IL-12 p40 gene, ultimately resulting in
      decreased IL-12 production following LPS stimulation.

PMID- 18322173
TI  - Monocyte cell surface glycosaminoglycans positively modulate IL-4-induced
      differentiation toward dendritic cells.
AB  - IL-4 induces the differentiation of monocytes toward dendritic cells (DCs). The
      activity of many cytokines is modulated by glycosaminoglycans (GAGs). In this
      study, we explored the effect of GAGs on the IL-4-induced differentiation of
      monocytes toward DCs. IL-4 dose-dependently up-regulated the expression of DC
      specific ICAM-3-grabbing nonintegrin (DC-SIGN), CD80, CD206, and CD1a. Monocytes
      stained positive with Abs against heparan sulfate (HS) and chondroitin sulfate
      (CS) B (CSB; dermatan sulfate), but not with Abs that recognize CSA, CSC, and
      CSE. Inhibition of sulfation of monocyte/DC cell surface GAGs by sodium chlorate
      reduced the reactivity of sulfate-recognizing single-chain Abs. This correlated
      with hampered IL-4-induced DC differentiation as evidenced by lower expression of
      DC-SIGN and CD1a and a decreased DC-induced PBL proliferation, suggesting that
      sulfated monocyte cell surface GAGs support IL-4 activity. Furthermore, removal
      of cell surface chondroitin sulfates by chondroitinase ABC strongly impaired IL-4
      induced STAT6 phosphorylation, whereas removal of HS by heparinase III had only a
      weak inhibitory effect. IL-4 bound to heparin and CSB, but not to HS, CSA, CSC,
      CSD, and CSE. Binding of IL-4 required iduronic acid, an N-sulfate group
      (heparin) and specific O sulfates (CSB and heparin). Together, these data
      demonstrate that monocyte cell surface chondroitin sulfates play an important
      role in the IL-4-driven differentiation of monocytes into DCs.

PMID- 18322174
TI  - Non-T cell activation linker promotes mast cell survival by dampening the
      recruitment of SHIP1 by linker for activation of T cells.
AB  - The linker for activation of T cells (LAT) and the non-T cell activation linker
      (NTAL) are two transmembrane adapters which organize IgE receptor (FcepsilonRI)
      signaling complexes in mast cells. LAT positively regulates, whereas NTAL
      negatively regulates mast cell activation. We previously found that the four
      distal tyrosines of LAT can generate negative signals. We show here that two of
      these tyrosines provide two binding sites for SHIP1, that LAT recruits SHIP1 in
      vivo, and that SHIP1 recruitment is enhanced in NTAL-deficient cells. We show
      that NTAL negatively regulates mast cell activation by decreasing the
      recruitment, by LAT, of molecules involved in FcepsilonRI-dependent positive
      signaling. We show that NTAL also decreases the recruitment of SHIP1 by LAT,
      leading to an increased phosphorylation of the antiapoptotic molecule Akt, and
      positively regulates mast cell survival. We finally show that the positive effect
      of NTAL on Akt phosphorylation and mast cell survival requires LAT. Our data thus
      document the mechanisms by which LAT and NTAL can generate both positive and
      negative signals which differentially regulate mast cell activation and survival.
      They also provide molecular bases for the recruitment of SHIP1 in FcepsilonRI
      signaling complexes. SHIP1 is a major negative regulator of mast cell activation
      and, hence, of allergic reactions.

PMID- 18322175
TI  - E2F4 modulates differentiation and gene expression in hematopoietic progenitor
      cells during commitment to the lymphoid lineage.
AB  - The E2F4 protein is involved in gene repression and cell cycle exit, and also has
      poorly understood effects in differentiation. We analyzed the impact of E2F4
      deficiency on early steps in mouse hematopoietic development, and found defects
      in early hematopoietic progenitor cells that were propagated through common
      lymphoid precursors to the B and T lineages. In contrast, the defects in
      erythromyeloid precursor cells were self-correcting over time. This suggests that
      E2F4 is important in early stages of commitment to the lymphoid lineage. The E2F4
      deficient progenitor cells showed reduced expression of several key lymphoid
      lineage genes, and overexpression of two erythromyeloid lineage genes. However,
      we did not detect effects on cell proliferation. These findings emphasize the
      significance of E2F4 in controlling gene expression and cell fate.

PMID- 18322176
TI  - Allelic and isotypic light chain inclusion in peripheral B cells from anti-DNA
      antibody transgenic C57BL/6 and BALB/c mice.
AB  - Most mature B lymphocytes express one BCR L chain, kappa or lambda, but recent
      work has shown that there are exceptions in that some B lymphocytes express both
      kappa and lambda and some even bear two different kappa L chains. Using the anti
      DNA H chain-transgenic mouse, 56R, we find that B cells with pre-existing
      autoreactivity are especially subject to L chain inclusion. Specifically, we show
      that isotypic and allelic inclusion enables autoreactive B cells to bypass
      central tolerance giving rise to B cells that retain dangerous features. One
      receptor in dual receptor B cells is an editor L chain, i.e., neutralizes or
      alters self-reactivity of the 56R H chain transgene. We compare the 56R mouse
      when on the C57/BL/6 background, a strain prone to autoimmunity, with that of 56R
      when on the BALB/c background, a strain that resists autoimmunity. In the B6.56R
      mouse, polyreactive B cells with dual L chain move to the follicular B cell
      compartment. Their localization in the follicular compartment may explain the
      ease with which B cells in the B6.56R differentiate into autoantibody-producing
      plasma cells. Likewise, in the BALB/c.56R mouse, dual L chain B cells are found
      in the follicular B cell compartment. Yet, the lack of autoantibody-producing
      plasma cells in the BALB/c.56R suggests that postfollicular tolerance checkpoints
      are intact. The Jkappa usage in dual kappa L chain B cells suggests increased
      receptor editing activity and is consistent with the expected distribution of
      Jkappa genes in our computational model for random selection of Jkappa.

PMID- 18322177
TI  - The use of filamentous bacteriophage fd to deliver MAGE-A10 or MAGE-A3 HLA-A2
      restricted peptides and to induce strong antitumor CTL responses.
AB  - Delivery of tumor-associated Ag-derived peptides in a high immunogenic form
      represents one of the key issues for effective peptide-based cancer vaccine
      development. We report herein the ability of nonpathogenic filamentous
      bacteriophage fd virions to deliver HLA-A2-restricted MAGE-A10(254-262)- or MAGE
      A3(271-279)-derived peptides and to elicit potent specific CTL responses in vitro
      and in vivo. Interestingly, human anti-MAGE-A3(271-279)-specific CTLs were able
      to kill human MAGE-A3(+) tumor cells, even if these cells naturally express a low
      amount of MAGE-A3(271-279) peptide-HLA epitope surface complexes and are usually
      not recognized by CTLs generated by conventional stimulation procedures. MAGE
      A3(271-279)-specific/CD8(+) CTL clones were isolated from in vitro cultures, and
      their high avidity for Ag recognition was assessed. Moreover, in vivo tumor
      protection assay showed that vaccination of humanized HHD (HLA-A2.1(+)/H2-D(b+))
      transgenic mice with phage particles expressing MAGE-A3(271-279)-derived peptides
      hampered tumor growth. Overall, these data indicate that engineered filamentous
      bacteriophage virions increase substantially the immunogenicity of delivered
      tumor-associated Ag-derived peptides, thus representing a novel powerful system
      for the development of effective peptide-based cancer vaccines.

PMID- 18322178
TI  - Identification of RNA sequence motifs stimulating sequence-specific TLR8
      dependent immune responses.
AB  - The TLRs 7, 8, and 9 stimulate innate immune responses upon recognizing pathogen
      nucleic acids. U-rich RNA sequences were recently discovered that stimulate human
      TLR7/8-mediated or murine TLR7-mediated immune effects. In this study we
      identified single-stranded RNA sequences containing defined sequence motifs that
      either preferentially activate human TLR8-mediated as opposed to TLR7- or TLR7/8
      mediated immune responses. The identified TLR8 RNA motifs signal via TLR8 and
      fail to induce IFN-alpha from TLR7-expressing plasmacytoid dendritic cells but
      induce the secretion of Th1-like and proinflammatory cytokines from TLR8
      expressing immune cells such as monocytes or myeloid dendritic cells. In
      contrast, RNA sequences containing the TLR7/8 motif signal via TLR7 and TLR8 and
      stimulate cytokine secretion from both TLR7- and TLR8-positive immunocytes. The
      TLR8-specific RNA sequences are able to trigger cytokine responses from human and
      bovine but not from mouse, rat, and porcine immune cells, suggesting that these
      species lack the capability to respond properly to TLR8 RNA ligands. In summary,
      we describe two classes of single-stranded TLR7/8 and TLR8 RNA agonists with
      diverse target cell and species specificities and immune response profiles.

PMID- 18322179
TI  - CD27 defines phenotypically and functionally different human NK cell subsets.
AB  - The absence of the TNF-receptor family member CD27 marks the stable acquisition
      of cytolytic effector functions by both CD4(+) and CD8(+) T cells. We found that
      the majority of circulating human NK cells was CD27(-). These cells were largely
      CD56(dim), contained high levels of perforin and granzyme B, and were able to
      exert strong cytotoxic activity. In contrast, circulating CD27(+) NK cells were
      mostly CD56(dim/bright), had significant lower levels of perforin and granzyme B,
      and had a low cytolytic potential. Primary and secondary lymphoid organs were
      markedly enriched for CD27(+) NK cells. When correlating the expression of CD27
      to recently defined developmental stages of NK cells in tonsil, we observed that
      CD27 was exclusively found on mature CD94(+), stage 4 NK cells. On these cells,
      regulation of CD27 expression appeared to be controlled by the common gamma-chain
      cytokine IL-15, and down-regulation of CD27 was specifically induced by its
      ligand, CD70. Thus, the absence of CD27 expression allows the definition of
      cytotoxic effector cells within the known mature NK cell subsets in humans.

PMID- 18322180
TI  - Loss of suppressor of cytokine signaling 1 in helper T cells leads to defective
      Th17 differentiation by enhancing antagonistic effects of IFN-gamma on STAT3 and
      Smads.
AB  - Suppressor of cytokine signaling 1 (SOCS1) is an important negative regulator for
      cytokines; however, the role of SOCS1 in Th17 differentiation has not been
      clarified. We generated T cell-specific SOCS1-deficient mice and found that these
      mice were extremely resistant to a Th17-dependent autoimmune disease model,
      experimental autoimmune encephalomyelitis. SOCS1-deficient naive CD4(+) T cells
      were predominantly differentiated into Th1 and poorly into Th17 in vitro. These
      phenotypes were canceled in IFN-gamma(-/-) background, suggesting that a large
      amount of IFN-gamma in SOCS1-deficient T cells suppressed Th17 differentiation.
      IL-6 plus TGF-beta enhanced retinoic acid receptor-related orphan receptor (ROR)
      gammat expression and suppressed IFN-gamma production in wild-type T cells,
      whereas these effects were severely impaired in SOCS1-deficient T cells. These
      phenotypes can be partly explained by STAT3 suppression by enhanced SOCS3
      induction through hyper-STAT1 activation in SOCS1-deficient T cells. In addition,
      SOCS1-deficient T cells were much less sensitive to TGF-beta. Suppression of Th1
      differentiation by TGF-beta was impaired in SOCS1-deficient T cells. TGF-beta
      mediated Smad transcriptional activity was severely inhibited in SOCS1-deficient
      cells in the presence of IFN-gamma. Such impairment of TGF-beta functions were
      not observed in SOCS3-overexpressed cells, indicating that suppression of Smads
      was independent of SOCS3. Therefore, SOCS1 is necessary for Th17 differentiation
      by suppressing antagonistic effect of IFN-gamma on both STAT3 and Smads.
      Induction of SOCS3 can partly explain IFN-gamma-mediated STAT3 suppression, while
      other mechanism(s) will be involved in IFN-gamma-mediated Smad suppression. SOCS1
      deficient T cells will be very useful to investigate the molecular mechanism for
      the STAT1-mediated suppression of Th17 development.

PMID- 18322181
TI  - IL-15 does not affect IEL development in the thymus but regulates homeostasis of
      putative precursors and mature CD8 alpha alpha+ IELs in the intestine.
AB  - Mice devoid of the IL-15 system lose over 90% of CD8alphaalpha(+) TCRalphabeta
      and TCRgammadelta intestinal intraepithelial lymphocytes (iIELs). Previous work
      revealed that IL-15Ralpha and IL-15 expressed by parenchymal cells, but not by
      bone marrow-derived cells, are required for normal CD8alphaalpha(+) iIEL
      homeostasis. However, it remains unclear when and how the IL-15 system affects
      CD8alphaalpha(+) iIELs through their development. This study found that IL
      15Ralpha is dispensable for the thymic stage of CD8alphaalpha(+) TCRalphabeta and
      TCRgammadelta iIEL development but is required for the maintenance and/or
      differentiation of the putative lineage marker negative precursors in the
      intestinal epithelium, especially for the most mature CD8 single positive subset.
      Moreover, the IL-15 system directly supports the survival of mature
      CD8alphaalpha(+) iIEL in vivo. Taken together, this study suggests that
      regulation of CD8alphaalpha(+) iIEL homeostasis by the IL-15 system does not
      occur in the thymus but involves mature cells and putative precursors in the
      intestine.

PMID- 18322182
TI  - Modulation of the tumor cell phenotype by IFN-gamma results in resistance of
      uveal melanoma cells to granule-mediated lysis by cytotoxic lymphocytes.
AB  - IFN-gamma, a pleiotropic immune regulator, is implicated in both tumor immune
      surveillance and selection of tumor variants resistant to immune control, i.e.,
      immunoediting. In uveal melanoma patients, elevated serum levels of IFN-gamma
      correlate with the spread of metastasis and represent a negative prognostic
      marker. Treatment with IFN-gamma boosted the MHC class I presentation machinery
      in uveal melanoma cells but suppressed their MHC class I-restricted CTL lysis.
      Tumor cells exposed to IFN-gamma efficiently activated specific CTL but were less
      susceptible to permeabilization by perforin and exhibited a decreased capacity to
      bind and incorporate granzyme B. These results define a novel mechanism of
      resistance to granule-mediated CTL lysis in human tumors. Furthermore, the data
      suggest that immunoediting is not limited to genetic or epigenetic changes
      resulting in stable cellular phenotypes but also involves an inducible modulation
      of tumor cells in response to a microenvironment associated with immune
      activation.

PMID- 18322183
TI  - Telomerase is involved in IL-7-mediated differential survival of naive and memory
      CD4+ T cells.
AB  - IL-7 plays an essential role in T cell maintenance and survival. The survival
      effect of IL-7 is thought to be mediated through regulation of Bcl2 family
      proteins. After a comparative analysis of IL-7-induced growth and cell death of
      human naive and memory CD4(+) T cells, we observed that more memory CD4(+) T
      cells underwent cell division and proceeded to apoptosis than naive cells in
      response to IL-7. However, IL-7-induced expressions of Bcl2 family members (Bcl2,
      Bcl-x(L), Bax, and Bad) were similar between naive and memory cells. Instead, we
      found that IL-7 induced higher levels of telomerase activity in naive cells than
      in memory cells, and the levels of IL-7-induced telomerase activity had a
      significant inverse correlation with cell death in CD4(+) T cells. Furthermore,
      we showed that reducing expression of telomerase reverse transcriptase and
      telomerase activity significantly increased cell death of IL-7-cultured CD4(+) T
      cells. Together, these findings demonstrate that telomerase is involved in IL-7
      mediated differential survival of naive and memory CD4(+) T cells.

PMID- 18322184
TI  - Human lymphocyte activation gene-3 molecules expressed by activated T cells
      deliver costimulation signal for dendritic cell activation.
AB  - Data have been reported on the in vivo adjuvant role of soluble lymphocyte
      activation gene-3 (LAG-3) recombinant protein in mouse models and on its ability
      to support the in vitro generation of human, tumor-specific CTLs. In this study,
      we show that soluble human rLAG-3 protein (hLAG-3Ig) used in vitro as a single
      maturation agent induces phenotypic maturation of monocyte-derived dendritic
      cells and promoted the production of chemokines and TNF-alpha inflammatory
      cytokine. When given in association with optimal or suboptimal doses of
      CD40/CD40L, hLAG-3Ig functions as a strong costimulatory factor and induces full
      functional activation of monocyte-derived dendritic cells that includes the
      production of high level of IL-12p70. Moreover, evidence is here provided that
      this costimulatory function licensing dendritic cells to produce IL-12p70 is also
      a functional property of LAG-3 molecules when expressed in a physiological
      context by CD4(+) activated T cells. Altogether, these data show for the first
      time a role of LAG-3 in mediating dendritic cell activation when expressed on the
      T cell surface or released after specific Ag stimulation in the interspaces of
      immunological synapses.

PMID- 18322185
TI  - IFN-beta provides immuno-protection in the retina by inhibiting ICAM-1 and CXCL9
      in retinal pigment epithelial cells.
AB  - The retinal pigment epithelial (RPE) cell is a potent regulatory cell that
      facilitates normal physiologic processes and plays a critical role in a variety
      of retinal diseases. We evaluated IFN-beta production in human RPE cells through
      TLR signaling and investigated the effects of IFN-beta on RPE cells. RPE cells
      treated with poly(I:C) or infected with an RNA virus produce IFN-beta. Kinetic
      studies revealed that IFN-beta levels continue to increase over a 48-h period and
      this was associated with the up-regulation of IRF-7 gene expression, a known
      positive feedback molecule for IFN-beta production. Microarray analysis revealed
      that in IFN-beta treated cells, 480 genes of 22,283 genes were up or down
      regulated by >2-fold. We hypothesize that IFN-beta induction during TLR signaling
      in the retina is an immunosuppressive factor produced to limit immunopathologic
      damage. Cytokine activation of RPE cells results in the production of the
      chemokines, CXCL9 and CXCL10, and the adhesion molecule, ICAM-1. Pretreatment of
      RPE cells with IFN-beta resulted in inhibition of ICAM-1 production and
      elimination of CXCL9 production. This treatment did not alter CXCL10 production.
      Anti-IFN-beta Ab blocked the inhibitory action of IFN-beta. Real time PCR
      analysis revealed that IFN-beta treatment inhibited gene expression of sICAM-1
      and CXCL9. The results indicate a critical role for RPE cell derived IFN-beta in
      the down-regulation of CXCL9 and ICAM-1 expression in the retina and suggest that
      the inhibition of CXCL9 is an immuno-suppressive mechanism that protects the
      retina from excessive inflammation.

PMID- 18322186
TI  - Attenuating regulatory T cell induction by TLR agonists through inhibition of p38
      MAPK signaling in dendritic cells enhances their efficacy as vaccine adjuvants
      and cancer immunotherapeutics.
AB  - TLR ligands are potent adjuvants and promote Th1 responses to coadministered Ags
      by inducing innate IL-12 production. We found that TLR ligands also promote the
      induction of IL-10-secreting regulatory T (Treg) cells through p38 MAPK-induced
      IL-10 production by dendritic cells (DC). Inhibition of p38 suppressed TLR
      induced IL-10 and PGE(2) and enhanced IL-12 production in DC. Incubation of Ag
      pulsed CpG-stimulated DC with a p38 inhibitor suppressed their ability to
      generate Treg cells, while enhancing induction of Th1 cells. In addition,
      inhibition of p38 enhanced the antitumor therapeutic efficacy of DC pulsed with
      Ag and CpG and this was associated with an enhanced frequency of IFN-gamma
      secreting T cells and a reduction of Foxp3(+) Treg cells infiltrating the tumors.
      Furthermore, addition of a p38 inhibitor to a pertussis vaccine formulated with
      CpG enhanced its protective efficacy in a murine respiratory challenge model.
      These data demonstrate that the adjuvant activity of TLR agonists is compromised
      by coinduction of Treg cells, but this can be overcome by inhibiting p38
      signaling in DC. Our findings suggest that p38 is an important therapeutic target
      and provides a mechanism to enhance the efficacy of TLR agonists as vaccine
      adjuvants and cancer immunotherapeutics.

PMID- 18322187
TI  - A lupus-suppressor BALB/c locus restricts IgG2 autoantibodies without altering
      intrinsic B cell-tolerance mechanisms.
AB  - FcgammaR2B-deficient mice develop autoantibodies and glomerulonephritis with a
      pathology closely resembling human lupus when on the C57BL/6 (B6) background. The
      same mutation on the BALB/c background does not lead to spontaneous disease,
      suggesting differences in lupus susceptibility between the BALB/c and B6 strains.
      An F2 genetic analysis from a B6/BALB cross identified regions from the B6
      chromosomes 12 and 17 with positive linkage for IgG autoantibodies. We have
      generated a congenic strain that contains the suppressor allele from the BALB/c
      chromosome 12 centromeric region (sbb2(a)) in an otherwise B6.FcgammaR2B(-/-)
      background. None of the B6.FcgammaR2B(-/-)sbb2(a/a) mice tested have developed
      IgG autoantibodies in the serum or autoimmune pathology. Mixed bone marrow
      reconstitution experiments indicate that sbb2(a) is expressed in non-B bone
      marrow-derived cells and acts in trans. sbb2(a) does not alter L chain editing
      frequencies of DNA Abs in the 3H9H/56R H chain transgenic mice, but the level of
      IgG2a anti-DNA Abs in the serum is reduced. Thus, sbb2(a) provides an example of
      a non-MHC lupus-suppressor locus that protects from disease by restricting the
      production of pathogenic IgG isotypes even in backgrounds with inefficient Ab
      editing checkpoints.

PMID- 18322188
TI  - A novel B7-2 (CD86) splice variant with a putative negative regulatory role.
AB  - B7-2 (CD86) costimulatory molecules are pivotal for the regulation of T cell
      responses. In this study, a novel human B7-2 alternate transcript (termed B7-2C)
      is described. This transcript is characterized by the deletion of exon 4 that
      encodes the IgV-like counter-receptor binding domain of the B7-2 protein (full
      length; B7-2A). B7-2C was detected as mRNA and cell surface protein in human non
      neoplastic salivary gland epithelial cells and monocytes, but not in fibroblasts,
      T cells, B cells, dendritic cells, and several epithelial tumor cell lines. In
      monocytes, B7-2C protein expression was found to be significantly down-regulated
      following activation. The analysis of Chinese hamster ovary (CHO) single
      transfected (CHO-B7-2C) and double-transfected (CHO-B7-2A/B7-2C) cell lines had
      indicated that cell surface B7-2C expression is by itself unable to provide T
      cell costimulation, but inhibits the transmission of costimulatory signals via B7
      2A (by 23-69%). Such inhibition was found to depend on the relative cell surface
      expression of B7-2A and B7-2C proteins, as it occurred in CHO-B7-2A/B7-2C
      transfectants with significantly lower B7-2A to B7-2C ratios (1.0-3.5), compared
      with those with unaffected B7-2A-mediated costimulatory function (10.0-19.5). Our
      findings suggest that B7-2C is expressed by monocytes, as well as by nonimmune
      cells with potential Ag-presenting capacity (such as salivary gland epithelial
      cells). The expression of B7-2C on certain B7-2A-expressing cells appears to
      represent a mechanism for the fine tuning of B7-2A-mediated costimulatory
      signals, possibly through the interruption of B7-2A clustering required for the
      productive interaction between B7-2A and cognate receptors.

PMID- 18322189
TI  - A specific anti-Aire antibody reveals aire expression is restricted to medullary
      thymic epithelial cells and not expressed in periphery.
AB  - Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy is an autoimmune
      disorder caused by mutations in the autoimmune regulator gene AIRE. We examined
      the expression of Aire in different organs (thymus, spleen, and lymph nodes) in
      C57BL/6 mice, using a novel rat mAb, specific for murine Aire. Using flow
      cytometry, directly fluorochrome-labeled mAb revealed Aire expression in a rare
      thymic cellular subset that was CD45(-), expressed low levels of Ly51, and was
      high for MHC-II and EpCam. This subset also expressed a specific pattern of
      costimulatory molecules, including CD40, CD80, and PD-L1. Immunohistochemical
      analysis revealed that Aire(+) cells were specifically localized to the thymus
      or, more precisely, to the cortico-medulla junction and medulla, correlating with
      the site of negative selection. Although in agreement with previous studies, low
      levels of Aire mRNA was detected in all dendritic cell subtypes however lacZ
      staining, immunohistochemistry and flow cytometry failed to detect Aire protein.
      At a cellular level, Aire was expressed in perinuclear speckles within the
      nucleus. This report provides the first detailed analysis of Aire protein
      expression, highlighting the precise location at both the tissue and cellular
      level.

PMID- 18322190
TI  - Differential sensitivity to Itk kinase signals for T helper 2 cytokine production
      and chemokine-mediated migration.
AB  - Allergic asthma is dependent on chemokine-mediated Th2 cell migration and Th2
      cytokine secretion into the lungs. The inducible T cell tyrosine kinase Itk
      regulates the production of Th2 cytokines as well as migration in response to
      chemokine gradients. Mice lacking Itk are resistant to developing allergic
      asthma. However, the role of kinase activity of Itk in the development of this
      disease is unclear. In addition, whether distinct Itk-derived signals lead to T
      cell migration and secretion of Th2 cytokines is also unknown. Using transgenic
      mice specifically lacking Itk kinase activity, we show that active kinase
      signaling is required for control of Th2 responses and development of allergic
      asthma. Moreover, dominant suppression of kinase Itk activity led to normal Th2
      responses, but significantly reduced chemokine-mediated migration, resulting in
      prevention of allergic asthma. These observations indicate that signals required
      for Th2 responses and migration are differentially sensitive to Itk activity.
      Manipulation of Itk's activity can thus provide a new strategy to treat allergic
      asthma by differentially affecting migration of T cells into the lungs, leaving
      Th2 responses intact.

PMID- 18322191
TI  - Ig knock-in mice producing anti-carbohydrate antibodies: breakthrough of B cells
      producing low affinity anti-self antibodies.
AB  - Natural Abs specific for the carbohydrate Ag Galalpha1-3Galbeta1-4GlcNAc-R
      (alphaGal) play an important role in providing protective host immunity to
      various pathogens; yet little is known about how production of these or other
      anti-carbohydrate natural Abs is regulated. In this study, we describe the
      generation of Ig knock-in mice carrying functionally rearranged H chain and L
      chain variable region genes isolated from a B cell hybridoma producing alphaGal
      specific IgM Ab that make it possible to examine the development of B cells
      producing anti-carbohydrate natural Abs in the presence or absence of alphaGal as
      a self-Ag. Knock-in mice on a alphaGal-deficient background spontaneously
      developed alphaGal-specific IgM Abs of a sufficiently high titer to mediate
      rejection of alphaGal expressing cardiac transplants. In the spleen of these
      mice, B cells expressing alphaGal-specific IgM are located in the marginal zone.
      In knock-in mice that express alphaGal, B cells expressing the knocked in BCR
      undergo negative selection via receptor editing. Interestingly, production of low
      affinity alphaGal-specific Ab was observed in mice that express alphaGal that
      carry two copies of the knocked in H chain. We suggest that in these mice,
      receptor editing functioned to lower the affinity for self-Ag below a threshold
      that would result in overt pathology, while allowing development of low affinity
      anti-self Abs.

PMID- 18322192
TI  - First signature of islet beta-cell-derived naturally processed peptides selected
      by diabetogenic class II MHC molecules.
AB  - The diversity of Ags targeted by T cells in autoimmune diabetes is unknown. In
      this study, we identify and characterize a limited number of naturally processed
      peptides from pancreatic islet beta-cells selected by diabetogenic I-A(g7)
      molecules of NOD mice. We used insulinomas transfected with the CIITA
      transactivator, which resulted in their expression of class II histocompatibility
      molecules and activation of diabetogenic CD4 T cells. Peptides bound to I-A(g7)
      were isolated and examined by mass spectrometry: some peptides derived from
      proteins present in secretory granules of endocrine cells, and a number were
      shared with cells of neuronal lineage. All proteins to which peptides were
      identified were expressed in beta cells from normal islets. Peptides bound to I
      A(g7) molecules contained the favorable binding motif characterized by acidic
      amino acids at the P9 position. The draining pancreatic lymph nodes of
      prediabetic NOD mice contained CD4 T cells that recognized three different
      natural peptides. Furthermore, four different peptides elicited CD4 T cells,
      substantiating the presence of such self-reactive T cells. The overall strategy
      of identifying natural peptides from islet beta-cells opens up new avenues to
      evaluate the repertoire of self-reactive T cells and its role in onset of
      diabetes.

PMID- 18322193
TI  - Memory CD8+ T cells protect dendritic cells from CTL killing.
AB  - CD8(+) T cells have been shown to be capable of either suppressing or promoting
      immune responses. To reconcile these contrasting regulatory functions, we
      compared the ability of human effector and memory CD8(+) T cells to regulate
      survival and functions of dendritic cells (DC). We report that, in sharp contrast
      to the effector cells (CTLs) that kill DCs in a granzyme B- and perforin
      dependent mechanism, memory CD8(+) T cells enhance the ability of DCs to produce
      IL-12 and to induce functional Th1 and CTL responses in naive CD4(+) and CD8(+) T
      cell populations. Moreover, memory CD8(+) T cells that release the DC-activating
      factor TNF-alpha before the release of cytotoxic granules induce DC expression of
      an endogenous granzyme B inhibitor PI-9 and protect DCs from CTL killing with
      similar efficacy as CD4(+) Th cells. The currently identified DC-protective
      function of memory CD8(+) T cells helps to explain the phenomenon of CD8(+) T
      cell memory, reduced dependence of recall responses on CD4(+) T cell help, and
      the importance of delayed administration of booster doses of vaccines for the
      optimal outcome of immunization.

PMID- 18322194
TI  - Neuroprotective immunity: T cell-derived glutamate endows astrocytes with a
      neuroprotective phenotype.
AB  - A well-controlled T cell response to CNS injury may result in increased neuronal
      survival. However, the precise mechanism of T cell-induced neuroprotection is
      unknown. In this study, we report the unexpected finding that during culture of T
      cells, high levels of glutamate accumulate, which are efficiently cleared if T
      cells are cocultured with astrocytes. The T cell-derived glutamate elicits in
      turn, the release of neuroprotective thiols (cysteine, glutathione, and cysteinyl
      glycine) and lactate from astrocytes. Media obtained from astrocytes conditioned
      in the presence of T cells reduce neuronal apoptosis induced by oxidative stress
      in primary neuronal cultures from 48 +/- 14 to 9 +/- 4% (p < 0.001). Inhibition
      of glutamate-dependent signaling during astrocyte-T cell cocultivation by a
      glutamate uptake inhibitor, l-aspartic acid beta-hydroxamate, abolishes this
      neuroprotective effect. The ability of astrocytes to clear extracellular
      glutamate is impaired under conditions of oxidative stress. We demonstrate that T
      cells, via secreted cytokines, restore glutamate clearance capacity of astrocytes
      under oxidative conditions. Furthermore, under normoxic conditions, glutamate
      buffering capacity of astrocytes is increased upon cocultivation with T cells. It
      is known that, following CNS injury, astrocytes can respond with beneficial or
      destructive effects on neurons. However, the context and signaling mechanisms for
      this dual astrocytic response are unknown. Our results implicate T cells as
      potential determinants of the context that elicits a protective role for
      astrocytes in the damaged CNS.

PMID- 18322195
TI  - Intestinal epithelial cell up-regulation of LY6 molecules during colitis results
      in enhanced chemokine secretion.
AB  - In the healthy colon, intestinal epithelial cells (IEC) form a physical barrier
      separating the myriad of gut Ags from the cells of the immune system.
      Simultaneously, IEC use several mechanisms to actively maintain immunologic
      tolerance to nonpathogenic Ags, including commensal bacteria. However, during
      inflammatory bowel disease (IBD), the line of defense provided by IEC is
      breached, resulting in uncontrolled immune responses. As IEC are a principal
      mediator of immune responses in the gut, we were interested in discerning the
      gene expression pattern of IEC during development and progression of IBD. Laser
      capture microdissection and microarray analysis were combined to identify the LY6
      superfamily as strongly up-regulated genes in inflamed IEC of the colon in two
      models of murine colitis. Surface expression of LY6A and LY6C on IEC is induced
      by several cytokines present within the colitic gut, including IL-22 and IFN
      gamma. Furthermore, cross-linking of LY6C results in production of a number of
      chemokines which are known to be involved in the immunopathogenesis of IBD.
      Increased chemokine production was cholesterol dependent, suggesting a role for
      lipid raft structures in the mechanism. As such, LY6 molecules represent novel
      targets to down-regulate chemokine expression in the colon and limit subsequent
      inflammation associated with IBD.

PMID- 18322196
TI  - TLR agonists promote marginal zone B cell activation and facilitate T-dependent
      IgM responses.
AB  - Although IgM serves as a first barrier to Ag spreading, the cellular and
      molecular mechanisms following B lymphocyte activation that lead to IgM secretion
      are not fully understood. By virtue of their anatomical location, marginal zone
      (MZ) B cells rapidly generate Ag-specific IgM in response to blood-borne
      pathogens and play an important role in the protection against these potentially
      harmful Ags. In this study, we have explored the contribution of TLR agonists to
      MZ B cell activation and mobilization as well as their ability to promote primary
      IgM responses in a mouse model. We demonstrate that diverse TLR agonists
      stimulate MZ B cells to become activated and leave the MZ through pathways that
      are differentially dependent on MyD88 and IFN-alphabeta receptor signaling.
      Furthermore, in vivo stimulation of MZ B cells with TLR agonists led to a
      reduction in the expression of the sphingosine-1-phosphate (S1P) receptors
      expressed by MZ B cells and/or increased CD69 cell surface levels. Importantly,
      as adjuvants for a T cell-dependent protein Ag, TLR agonists were found to
      accelerate the kinetics but not magnitude of the Ag-specific IgM response.
      Together, these data demonstrate that in vivo TLR agonist treatment enhances the
      early production of Ag-specific IgM and activates MZ B cells to promote their
      relocation.

PMID- 18322197
TI  - Lipopolysaccharide-activated IL-10-secreting dendritic cells suppress
      experimental autoimmune uveoretinitis by MHCII-dependent activation of CD62L
      expressing regulatory T cells.
AB  - Dendritic cells (DC) are key regulators of immune responses. Mature DC are
      traditionally considered to be immunogenic, although there is accumulating
      evidence that they can also be tolerogenic and induce Ag-specific regulatory T
      cells (Tregs). However, the mechanism of this Treg induction and the site of Treg
      action in vivo are yet to be defined. In this study, using the experimental model
      of interphotoreceptor retinoid-binding protein peptide (1-20)-induced
      experimental autoimmune uveoretinitis, we show that s.c. inoculation of IRBP
      peptide-pulsed IL-10-producing LPS-activated mature DC (IL-10-DC) at one site
      (the cervical region) suppresses autoimmunity induced at a separate site (the
      inguinal region). Our data show that s.c. IL-10-DC correlates with an increase in
      the number of CD4(+)CD25(+)Foxp3(+) Tregs at the DC-draining lymph nodes (DC
      dLN). However, although MHCII(-/-) IL-10-DC also induces Treg expansion at this
      DC-dLN, they failed to suppress experimental autoimmune uveoretinitis.
      Furthermore, unlike wild-type IL-10-DC, MHCII(-/-) IL-10-DC did not correlate
      with an increase in the percentage of Tregs expressing CD62L at the DC-dLN, nor
      did they associate with an increase in Treg number at a distal site. Similar
      effects were also observed after s.c. hen egg lysozyme-pulsed IL-10-DC, which
      produced a strong reduction in the number and activation of proliferating Ag
      specific CD4(+) 3A9 T effector cells. We therefore propose that IL-10-DC require
      MHCII-dependent Ag presentation, and hence TCR ligation, to promote CD62L
      mediated trafficking of Tregs to the site of T effector cell priming, where they
      suppress autoimmunity.

PMID- 18322198
TI  - A role for CD8 in the developmental tuning of antigen recognition and CD3
      conformational change.
AB  - TCR engagement by peptide-MHC class I (pMHC) ligands induces a conformational
      change (Deltac) in CD3 (CD3Deltac) that contributes to T cell signaling. We found
      that when this interaction took place between primary T lineage cells and APCs,
      the CD8 coreceptor was required to generate CD3Deltac. Interestingly, neither
      enhancement of Ag binding strength nor Src kinase signaling explained this
      coreceptor activity. Furthermore, Ag-induced CD3Deltac was developmentally
      attenuated by the increase in sialylation that accompanies T cell maturation and
      limits CD8 activity. Thus, both weak and strong ligands induced CD3Deltac in
      preselection thymocytes, but only strong ligands were effective in mature T
      cells. We propose that CD8 participation in the TCR/pMHC interaction can
      physically regulate CD3Deltac induction by "translating" productive Ag encounter
      from the TCR to the CD3 complex. This suggests one mechanism by which the
      developmentally regulated variation in CD8 sialylation may contribute to the
      developmental tuning of T cell sensitivity.

PMID- 18322199
TI  - Homeostatic proliferation of lymphocytes results in augmented memory-like
      function and accelerated allograft rejection.
AB  - Homeostatic proliferation is a normal physiological process triggered by
      lymphopenia to maintain a constant level of T cells. It becomes the predominant
      source of new T cells in adulthood after thymus regression. T cells that have
      undergone homeostatic proliferation acquire the memory phenotype, cause
      autoimmune disease, and are resistant to tolerance induction protocols.
      Transplantation is a rare example in which lymphopenia is deliberately induced
      for its immunosuppressive effect. However, it is not known whether the
      homeostatic proliferation that follows will have the opposite effect and
      accelerate rejection. We show that T cells that have undergone homeostatic
      proliferation acquire a memory phenotype, spontaneously skews toward the Th1
      phenotype, even in the absence of antigenic stimulus. Interestingly, in contrast,
      the percentage of Foxp3(+) regulatory T cells increased by 28-fold following
      homeostatic proliferation. Using a mouse life-sustaining kidney transplant model,
      we showed that T cells that have gone through homeostatic proliferation in
      lymphopenic hosts transformed chronic rejection to acute rejection of a single
      MHC class II-mismatched kidney allograft. T cells that have undergone homeostatic
      proliferation consistently cause reliable rejection even when bona fide memory T
      cells cannot. These functional changes are long-lasting and not restricted to the
      acute phase of homeostatic proliferation. Our findings have important
      implications for tolerance induction or graft-prolonging protocols involving
      leukocyte depletion such as irradiation bone marrow chimera, T cell-depleting
      Abs, and lymphopenia induced by infections such as CMV and HIV.

PMID- 18322200
TI  - Postnatal life events affect the severity of asthmatic airway inflammation in the
      adult rat.
AB  - Genetic and hygienic factors influence susceptibility to asthma. In autoimmune
      and inflammatory diseases, additional effects of the psychosocial environment
      have been demonstrated that might also play a role in asthma. In this study, the
      impact of different early postnatal stressors on an OVA-induced model of asthma
      was tested in adulthood. Fischer 344 rats were subjected to either repeated
      handling stimulation (HA), maternal separation (MS), or were left undisturbed in
      their first 4 wk of life. Behavioral differences were characterized at the age of
      4 mo. At 5 mo of age, immunological cellular and serologic changes were
      investigated and experimental asthma was induced. Results show significantly
      increased exploratory behavior and reduced anxiety in HA rats compared with MS
      and controls. Without further behavioral or immunological challenges, HA animals
      exhibited an increased ex vivo NK cell cytotoxicity but no other obvious
      immunological differences. After induction of asthma, in contrast, MS animals
      exhibited proinflammatory effects in leukocyte subset composition including
      increased eosinophil numbers, whereas levels of IgE and the allergy-specific
      cytokine IL-13 were reduced compared with HA. There was a most remarkable
      increase of adrenocorticotropin in HA animals, comparing pre- to postchallenge
      plasma levels. These data demonstrate for the first time that early postnatal
      stimulative or adverse experiences exert long-lasting changes of the
      "neuroendocrinoimmune" interface in adulthood, resulting in either protective or
      aggravating mechanisms in allergic airway disease. Thus, in addition to genetic
      and hygienic factors, nongenetically acquired individual differences contribute
      to the pathobiology of asthma.

PMID- 18322201
TI  - Structural and biological basis of CTL escape in coronavirus-infected mice.
AB  - Cytotoxic T lymphocyte escape occurs in many human infections, as well as mice
      infected with the JHM strain of mouse hepatitis virus, which exhibit CTL escape
      variants with mutations in a single epitope from the spike glycoprotein (S510).
      In all CTL epitopes prone to escape, only a subset of all potential variants is
      generally detected, even though many of the changes that are not selected would
      result in evasion of the T cell response. It is postulated that these unselected
      mutations significantly impair virus fitness. To define more precisely the basis
      for this preferential selection, we combine x-ray crystallographic studies of the
      MHC class I (D(b))/S510 complexes with viral reverse genetics to identify a
      prominent TCR contact residue (tryptophan at position 4) prone to escape
      mutations. The data show that a mutation that is commonly detected in chronically
      infected mice (tryptophan to arginine) potently disrupts the topology of the
      complex, explaining its selection. However, other mutations at this residue,
      which also abrogate the CTL response, are never selected in vivo even though they
      do not compromise virus fitness in acutely infected animals or induce a
      significant de novo CTL response. Thus, while structural analyses of the
      S510/D(b) complex provide a strong basis for why some CTL escape variants are
      selected, our results also show that factors other than effects on virus fitness
      limit the diversification of CD8 T cell epitopes.

PMID- 18322202
TI  - Filamin A stabilizes Fc gamma RI surface expression and prevents its lysosomal
      routing.
AB  - Filamin A, or actin-binding protein 280, is a ubiquitously expressed cytosolic
      protein that interacts with intracellular domains of multiple receptors to
      control their subcellular distribution, and signaling capacity. In this study, we
      document interaction between FcgammaRI, a high-affinity IgG receptor, and filamin
      A by yeast two-hybrid techniques and coimmunoprecipitation. Both proteins
      colocalized at the plasma membrane in monocytes, but dissociated upon FcgammaRI
      triggering. The filamin-deficient cell line M2 and a filamin-reconstituted M2
      subclone (A7), were used to further study FcgammaRI-filamin interactions.
      FcgammaRI transfection in A7 cells with filamin resulted in high plasma membrane
      expression levels. In filamin-deficient M2 cells and in filamin RNA-interference
      studies, FcgammaRI surface expression was consistently reduced. FcgammaRI
      localized to LAMP-1-positive vesicles in the absence of filamin as shown by
      confocal microscopy indicative for lysosomal localization. Mouse IgG2a capture
      experiments suggested a transient membrane expression of FcgammaRI before being
      transported to the lysosomes. These data support a pivotal role for filamin in
      FcgammaRI surface expression via retention of FcgammaRI from a default lysosomal
      pathway.

PMID- 18322203
TI  - Structural insight into the function of myelin basic protein as a ligand for
      integrin alpha M beta 2.
AB  - Multiple sclerosis (MS) is an inflammatory disease where phagocytic cells
      infiltrate the nerve tissue and act as terminal agents in destruction of the
      myelin sheath. However, the mechanism that triggers the ability of these cells to
      recognize myelin remains obscure. We show that myelin basic protein (MBP), a
      major autoantigen in MS, is a potent and specific ligand for the integrin
      alpha(M)beta(2) (Mac-1, CD11b/CD18) expressed mainly on phagocytic cells. MBP
      undergoes a dramatic conformational change when liberated from the lipid-rich
      environment of the myelin sheath. The MS drug glatiramer acetate mimics the
      conformationally labile regions of MBP, interacts in the unfolded state strongly
      with alpha(M)beta(2), and inhibits the MBP binding to alpha(M)beta(2). Our study
      reveals a link between MBP, glatiramer acetate, and the alpha(M)beta(2) integrin,
      and suggests a new model for MS pathogenesis based on the recognition of unfolded
      MBP by the alpha(M)beta(2) integrin.

PMID- 18322204
TI  - Autoantibody profiling in multiple sclerosis reveals novel antigenic candidates.
AB  - An important contribution of B cells and autoantibodies has been demonstrated in
      the pathogenesis of multiple sclerosis (MS), leading to interest in the use of
      such autoantibodies as diagnostic or prognostic biomarkers. The objective of this
      study was to identify novel Ab biomarkers for MS using "serological Ag
      selection". Using a phage display library derived from MS brain plaques, we
      applied serological Ag selection to identify antigenic targets specifically
      interacting with Abs present in the cerebrospinal fluid (CSF) of 10 relapsing
      remitting MS patients. These antigenic targets were further evaluated on a large
      panel of CSF from 63 other MS patients, 30 patients with other inflammatory
      disorders, and 64 patients with noninflammatory neurological disorders. A panel
      of eight antigenic targets was identified that showed a 86% specificity and 45%
      sensitivity in discriminating MS patients and controls. Four of the antigenic
      targets showed exclusive reactivity (100% specificity; 23% sensitivity) in the MS
      group as compared with the control group. Detailed bio-informatic analyses
      revealed a novel Ag, SPAG16. Among the novel phage peptides identified, novel
      epitopes were generated from untranslated sequences and out-of-frame sequences.
      Of 10 relapsing-remitting patients used for serological Ag selection, Ab
      reactivity toward one of the eight antigenic targets was also demonstrated in
      serum of 38% CSF-positive patients. Autoantibody profiles against epitopes
      derived from MS brain tissue could serve as diagnostic markers or form the basis
      for the identification of a subgroup of MS patients.

PMID- 18322205
TI  - A novel mechanism of complement inhibition unmasked by a tick salivary protein
      that binds to properdin.
AB  - Ixodes scapularis salivary protein 20 (Salp20) is a member of the Ixodes
      scapularis anti-complement protein-like family of tick salivary proteins that
      inhibit the alternative complement pathway. In this study, we demonstrate that
      the target of Salp20 is properdin. Properdin is a natural, positive regulator of
      the alternative pathway that binds to the C3 convertase, stabilizing the
      molecule. Salp20 directly bound to and displaced properdin from the C3
      convertase. Displacement of properdin accelerated the decay of the C3 convertase,
      leading to inhibition of the alternative pathway. S20NS is distinct from known
      decay accelerating factors, such as decay accelerating factor, complement
      receptor 1, and factor H, which directly interact with either C3b or cleaved
      factor B.

PMID- 18322206
TI  - Synergistic polymorphism at two positions distal to the ligand-binding site makes
      KIR2DL2 a stronger receptor for HLA-C than KIR2DL3.
AB  - Interactions between HLA-C ligands and inhibitory killer cell Ig-like receptors
      (KIR) control the development and response of human NK cells. This regulatory
      mechanism is usually described by mutually exclusive interactions of KIR2DL1 with
      C2 having lysine 80, and KIR2DL2/3 with C1 having asparagine 80. Consistent with
      this simple rule, we found from functional analysis and binding assays to 93 HLA
      A, HLA-B, and HLA-C isoforms that KIR2DL1*003 bound all C2, and only C2,
      allotypes. The allotypically related KIR2DL2*001 and KIR2DL3*001 interacted with
      all C1, but they violated the simple rule through interactions with several C2
      allotypes, notably Cw*0501 and Cw*0202, and two HLA-B allotypes (B*4601 and
      B*7301) that share polymorphisms with HLA-C. Although the specificities of the
      "cross-reactions" were similar for KIR2DL2*001 and KIR2DL3*001, they were
      stronger for KIR2DL2*001, as were the reactions with C1. Mutagenesis explored the
      avidity difference between KIR2DL2*001 and KIR2DL3*001. Recombinant mutants
      mapped the difference to the Ig-like domains, where site-directed mutagenesis
      showed that the combination, but not the individual substitutions, of arginine
      for proline 16 in D1 and cysteine for arginine 148 in D2 made KIR2DL2*001 a
      stronger receptor than KIR2DL3*001. Neither residue 16 or 148 is part of, or near
      to, the ligand-binding site. Instead, their juxtaposition near the flexible hinge
      between D1 and D2 suggests that their polymorphisms affect the ligand-binding
      site by changing the hinge angle and the relative orientation of the two domains.
      This study demonstrates how allelic polymorphism at sites distal to the ligand
      binding site of KIR2DL2/3 has diversified this receptor's interactions with HLA
      C.

PMID- 18322207
TI  - Functional maturation of the human antibody response to rotavirus.
AB  - Infant Abs induced by viruses exhibit poor functional activity compared with
      those of adults. The human B cell response to rotavirus is dominated by use of
      the V(H)1-46 gene segment in both adults and infants, but only adult sequences
      are highly mutated. We investigated in detail the kinetic, structural, and
      functional advantage conferred by individual naturally occurring somatic
      mutations in rotavirus-specific human Abs encoded by the immunodominant V(H)1-46
      gene segment. Adult Abs achieved enhanced binding through naturally occurring
      somatic mutations in the H chain CDR2 region that conferred a markedly prolonged
      off-rate and a desirable increase in antiviral potency. Three-dimensional
      cryoelectron microscopy studies of Ag-Ab complexes revealed the mechanism of
      viral inhibition to be the binding of high-affinity Abs at the viral RNA release
      pore in the double-layer particle. These structure-function studies suggest a
      molecular basis for the poor quality of Abs made in infancy following virus
      infection or immunization.

PMID- 18322208
TI  - Sporozoite-mediated hepatocyte wounding limits Plasmodium parasite development
      via MyD88-mediated NF-kappa B activation and inducible NO synthase expression.
AB  - Plasmodium sporozoites traverse several host cells before infecting hepatocytes.
      In the process, the plasma membranes of the cells are ruptured, resulting in the
      release of cytosolic factors into the microenvironment. This released endogenous
      material is highly stimulatory/immunogenic and can serve as a danger signal
      initiating distinct responses in various cells. Thus, our study aimed at
      characterizing the effect of cell material leakage during Plasmodium infection on
      cultured mouse primary hepatocytes and HepG2 cells. We observed that wounded cell
      derived cytosolic factors activate NF-kappaB, a main regulator of host
      inflammatory responses, in cells bordering wounded cells, which are potential
      host cells for final parasite infection. This activation of NF-kappaB occurred
      shortly after infection and led to a reduction of infection load in a time
      dependent manner in vitro and in vivo, an effect that could be reverted by
      addition of the specific NF-kappaB inhibitor BAY11-7082. Furthermore, no NF
      kappaB activation was observed when Spect(-/-) parasites, which are devoid of
      hepatocyte traversing properties, were used. We provide further evidence that NF
      kappaB activation causes the induction of inducible NO synthase expression in
      hepatocytes, and this is, in turn, responsible for a decrease in Plasmodium
      infected hepatocytes. Furthermore, primary hepatocytes from MyD88(-/-) mice
      showed no NF-kappaB activation and inducible NO synthase expression upon
      infection, suggesting a role of the Toll/IL-1 receptor family members in sensing
      cytosolic factors. Indeed, lack of MyD88 significantly increased infection in
      vitro and in vivo. Thus, host cell wounding due to parasite migration induces
      inflammation which limits the extent of parasite infection.

PMID- 18322209
TI  - Suppression of an already established tumor growing through activated mucosal
      CTLs induced by oral administration of tumor antigen with cholera toxin.
AB  - Priming of CTLs at mucosal sites, where various tumors are originated, seems
      critical for controlling tumors. In the present study, the effect of the oral
      administration of OVA plus adjuvant cholera toxin (CT) on the induction of Ag
      specific mucosal CTLs as well as their effect on tumor regression was
      investigated. Although OVA-specific TCRs expressing lymphocytes requiring in
      vitro restimulation to gain specific cytotoxicity could be detected by OVA
      peptide-bearing tetramers in both freshly isolated intraepithelial lymphocytes
      and spleen cells when OVA was orally administered CT, those showing direct
      cytotoxic activity without requiring in vitro restimulation were dominantly
      observed in intraepithelial lymphocytes. The magnitude of such direct
      cytotoxicity at mucosal sites was drastically enhanced after the second oral
      administration of OVA with intact whole CT but not with its subcomponent, an A
      subunit (CTA) or a B subunit (CTB). When OVA plus CT were orally administrated to
      C57BL/6 mice bearing OVA-expressing syngeneic tumor cells, E.G7-OVA, in either
      gastric tissue or the dermis, tumor growth was significantly suppressed after the
      second oral treatment; however, s.c. or i.p. injection of OVA plus CT did not
      show any remarkable suppression. Those mucosal OVA-specific CTLs having direct
      cytotoxicity expressed CD8alphabeta but not CD8alphaalpha, suggesting that they
      originated from thymus-educated cells. Moreover, the infiltration of such OVA
      specific CD8(+) CTLs was observed in suppressed tumor tissues. These results
      indicate that the growth of ongoing tumor cells can be suppressed by activated
      CD8alphabeta CTLs with tumor-specific cytotoxicity via an orally administered
      tumor Ag with a suitable mucosal adjuvant.

PMID- 18322210
TI  - Identification of an N-linked glycosylation in the C4 region of HIV-1 envelope
      gp120 that is critical for recognition of neighboring CD4 T cell epitopes.
AB  - The heavy glycosylation of HIV-1 envelope gp120 shields this important Ag from
      recognition by neutralizing Abs and cytolytic CD8 T cells. However, very little
      work has been done to understand the influence of glycosylation on the generation
      of gp120 epitopes and their recognition by MHC class II-restricted CD4 T cells.
      In this study, three conserved glycans (linked to N406, N448, and N463) flanking
      the C4 region of gp120 that contains many known CD4 T cell epitopes were
      disrupted individually or in combination by asparagine-to-glutamine
      substitutions. The mutant proteins lacking the N448 glycan did not effectively
      stimulate CD4 T cells specific for the nearby C4 epitopes, although the same
      mutants were recognized well by CD4 T cells specific for epitopes located in the
      distant C1 and C2 regions. The loss of recognition was not due to amino acid
      substitutions introduced to the mutant proteins. Data from trypsin digestion and
      mass spectrometry analyses demonstrated that the N448 glycan removal impeded the
      proteolytic cleavage of the nearby C4 region, without affecting more distant
      sites. Importantly, this inhibitory effect was observed only in the digestion of
      the native nondenatured protein and not in that of the denatured protein. These
      data indicate that the loss of the N448 glycan induces structural changes in the
      C4 region of gp120 that make this specific region more resistant to proteolytic
      processing, thereby restricting the generation of CD4 T cell epitopes from this
      region. Hence, N-linked glycans are critical determinants that can profoundly
      influence CD4 T cell recognition of HIV-1 gp120.

PMID- 18322211
TI  - Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection.
AB  - TLRs contribute to the inflammatory response in fungal infections. Although
      inflammation is an essential component of the protective response to fungi, its
      dysregulation may significantly worsen fungal diseases. In this study, we tested
      the hypothesis that Toll IL-1R8 (TIR8)/single Ig IL-1-related receptor, a member
      of the IL-1R family acting as a negative regulator of TLR/IL-1R signaling,
      affects TLR responses in fungal infections. Genetically engineered Tir8(-/-) mice
      were assessed for inflammatory and adaptive Th cell responses to Candida albicans
      and Aspergillus fumigatus. Inflammatory pathology and susceptibility to infection
      were higher in Tir8(-/-) mice and were causally linked to the activation of the
      Th17 pathway. IL-1R signaling was involved in Th17 cell activation by IL-6 and
      TGF-beta in that limited inflammatory pathology and relative absence of Th17 cell
      activation were observed in IL-1RI(-/-) mice. These data demonstrate that TIR8 is
      required for host resistance to fungal infections and that it functions to
      negatively regulate IL-1-dependent activation of inflammatory Th17 responses.
      TIR8 may contribute toward fine-tuning the balance between protective immunity
      and immunopathology in infection.

PMID- 18322212
TI  - Potent antimycobacterial activity of mouse secretory leukocyte protease
      inhibitor.
AB  - Secretory leukocyte protease inhibitor (SLPI) has multiple functions, including
      inhibition of protease activity, microbial growth, and inflammatory responses. In
      this study, we demonstrate that mouse SLPI is critically involved in innate host
      defense against pulmonary mycobacterial infection. During the early phase of
      respiratory infection with Mycobacterium bovis bacillus Calmette-Guerin, SLPI was
      produced by bronchial and alveolar epithelial cells, as well as alveolar
      macrophages, and secreted into the alveolar space. Recombinant mouse SLPI
      effectively inhibited in vitro growth of bacillus Calmette-Guerin and
      Mycobacterium tuberculosis through disruption of the mycobacterial cell wall
      structure. Each of the two whey acidic protein domains in SLPI was sufficient for
      inhibiting mycobacterial growth. Cationic residues within the whey acidic protein
      domains of SLPI were essential for disruption of mycobacterial cell walls. Mice
      lacking SLPI were highly susceptible to pulmonary infection with M. tuberculosis.
      Thus, mouse SLPI is an essential component of innate host defense against
      mycobacteria at the respiratory mucosal surface.

PMID- 18322213
TI  - SOCS-1 protects against Chlamydia pneumoniae-induced lethal inflammation but
      hampers effective bacterial clearance.
AB  - Suppressor of cytokine signaling 1 (SOCS1) plays a major role in the inhibition
      of STAT1-mediated responses. STAT1-dependent responses are critical for
      resistance against infection with Chlamydia pneumoniae. We studied the regulation
      of expression of SOCS1 and SOCS3, and the role of SOCS1 during infection with C.
      pneumoniae in mice. Bone marrow-derived macrophages (BMM) and dendritic cells in
      vitro or lungs in vivo all showed enhanced STAT1-dependent SOCS1 mRNA
      accumulation after infection with C. pneumoniae. Infection-increased SOCS1 mRNA
      levels were dependent on IFN-alphabeta but not on IFN-gamma. T or B cells were
      not required for SOCS1 mRNA accumulation in vivo. Infection-induced STAT1
      phosphorylation occurred more rapidly in SOCS1(-/-) BMM. In agreement, expression
      of IFN-gamma responsive genes, but not IL-1beta, IL-6, or TNF-alpha were
      relatively increased in C. pneumoniae-infected SOCS1(-/-) BMM. Surprisingly, C.
      pneumoniae infection-induced IFN-alpha, IFN-beta, and IFN-gamma expression in BMM
      were attenuated by SOCS1. C. pneumoniae infection of RAG1(-/-)/SOCS1(-/-) mice
      induced a rapid lethal inflammation, accompanied by diminished pulmonary
      bacterial load and increased levels of iNOS and IDO but not IL-1beta, IL-6, or
      TNF-alpha mRNA. In summary, C. pneumoniae infection induces a STAT1, IFN
      alphabeta-dependent and IFN-gamma independent SOCS1 mRNA accumulation. Presence
      of SOCS1 controls the infection-induced lethal inflammatory disease but impairs
      the bacterial control.

PMID- 18322214
TI  - Pannexin-1-mediated intracellular delivery of muramyl dipeptide induces caspase-1
      activation via cryopyrin/NLRP3 independently of Nod2.
AB  - Muramyl dipeptide (MDP), the microbial activator of nucleotide-binding
      oligomerization domain 2 (Nod2), induces NF-kappaB and MAPK activation, leading
      to the production of multiple anti-bacterial and proinflammatory molecules. In
      addition, MDP has been implicated in IL-1beta secretion through the regulation of
      caspase-1. However, the mechanisms that mediate caspase-1 activation and IL-1beta
      secretion in response to MDP stimulation remain poorly understood. We show here
      that fluorescent MDP molecules are internalized in primary macrophages and
      accumulate in granular structures that colocalize with markers of acidified
      endosomal compartments. The uptake of MDP was Nod2-independent. Upon ATP
      stimulation, labeled MDP was rapidly released from acidified vesicles into the
      cytosol, a process that required functional pannexin-1. Caspase-1 activation
      induced by MDP and ATP required pannexin-1 and Cryopyrin but was independent of
      Nod2. Conversely, induction of pro-IL-1beta mRNA by MDP stimulation was abolished
      in Nod2-deficient macrophages but unimpaired in macrophages lacking Cryopyrin.
      These studies demonstrate a Nod2-independent mechanism mediated through pore
      forming pannexin-1 that is required for intracellular delivery of MDP to the
      cytosol and caspase-1 activation. Furthermore, the work provides evidence for
      distinct roles of Nod2 and Cryopyrin in the regulation of MDP-induced caspase-1
      activation and IL-1beta secretion.

PMID- 18322215
TI  - Functional CD8+ T cell responses in lethal Ebola virus infection.
AB  - Ebola virus (EBOV) causes highly lethal hemorrhagic fever that leads to death in
      up to 90% of infected humans. Like many other infections, EBOV induces massive
      lymphocyte apoptosis, which is thought to prevent the development of a functional
      adaptive immune response. In a lethal mouse model of EBOV infection, we show that
      there is an increase in expression of the activation/maturation marker CD44 in
      CD4(+) and CD8(+) T cells late in infection, preceding a dramatic rebound of
      lymphocyte numbers in the blood. Furthermore, we observed both lymphoblasts and
      apoptotic lymphocytes in spleen late in infection, suggesting that there is
      lymphocyte activation despite substantial bystander apoptosis. To test whether
      these activated lymphocytes were functional, we performed adoptive transfer
      studies. Whole splenocytes from moribund day 7 EBOV-infected animals protected
      naive animals from EBOV, but not Marburgvirus, challenge. In addition, we
      observed EBOV-specific CD8(+) T cell IFN-gamma responses in moribund day 7 EBOV
      infected mice, and adoptive transfer of CD8(+) T cells alone from day 7 mice
      could confer protection to EBOV-challenged naive mice. Furthermore, CD8(+) cells
      from day 7, but not day 0, mice proliferated after transfer to infected
      recipients. Therefore, despite significant lymphocyte apoptosis, a functional and
      specific, albeit insufficient, adaptive immune response is made in lethal EBOV
      infection and is protective upon transfer to naive infected recipients. These
      findings should cause a change in the current view of the 'impaired' immune
      response to EBOV challenge and may help spark new therapeutic strategies to
      control lethal filovirus disease.

PMID- 18322216
TI  - Deoxynucleic acids from Cryptococcus neoformans activate myeloid dendritic cells
      via a TLR9-dependent pathway.
AB  - The mechanism of host cell recognition of Cryptococcus neoformans, an
      opportunistic fungal pathogen in immunocompromised patients, remains poorly
      understood. In the present study, we asked whether the DNA of this yeast
      activates mouse bone marrow-derived myeloid dendritic cells (BM-DCs). BM-DCs
      released IL-12p40 and expressed CD40 upon stimulation with cryptococcal DNA, and
      the response was abolished by treatment with DNase, but not with RNase. IL-12p40
      production and CD40 expression were attenuated by chloroquine, bafilomycin A, and
      inhibitory oligodeoxynucleotides (ODN) that suppressed the responses caused by
      CpG-ODN. Activation of BM-DCs by cryptococcal DNA was almost completely abrogated
      in TLR9 gene-disrupted (TLR9(-/-)) mice and MyD88(-/-) mice, similar to that by
      CpG-ODN. In addition, upon stimulation with whole yeast cells of acapsular C.
      neoformans, TLR9(-/-) BM-DCs produced a lower amount of IL-12p40 than those from
      wild-type mice, and TLR9(-/-) mice were more susceptible to pulmonary infection
      with this fungal pathogen than wild-type mice, as shown by increased number of
      live colonies in lungs. Treatment of cryptococcal DNA with methylase resulted in
      reduced IL-12p40 synthesis by BM-DCs. Furthermore, using a luciferase reporter
      assay, cryptococcal DNA activated NF-kappaB in HEK293 cells transfected with the
      TLR9 gene. Finally, confocal microscopy showed colocalization of fluorescence
      labeled cryptococcal DNA with CpG-ODN and the findings merged in part with the
      distribution of TLR9 in BM-DCs. Our results demonstrate that cryptococcal DNA
      causes activation of BM-DCs in a TLR9-dependent manner and suggest that the CpG
      motif-containing DNA may contribute to the development of inflammatory responses
      after infection with C. neoformans.

PMID- 18322217
TI  - Functional adaptation of Nef to the immune milieu of HIV-1 infection in vivo.
AB  - Nef-mediated down-regulation of MHC class I (MHC-I) molecules on HIV-1-infected
      cells has been proposed to enhance viral persistence through evasion of host
      CTLs. This conclusion is based largely on demonstrations that Nef from laboratory
      HIV-1 strains reduces the susceptibility of infected cells to CTL killing in
      vitro. However, the function and role of Nef-mediated MHC-I down-regulation in
      vivo have not been well described. To approach this issue, nef quasispecies from
      chronically HIV-1-infected individuals were cloned into recombinant reporter
      viruses and tested for their ability to down-regulate MHC-I molecules from the
      surface of infected cells. The level of function varied widely between
      individuals, and although comparison to the immunologic parameters of blood
      CD4(+) T lymphocyte count and breadth of the HIV-1-specific CTL response showed
      positive correlations, no significant correlation was found in comparison to
      plasma viremia. The ability of in vivo-derived Nef to down-regulate MHC-I
      predicted the resistance of HIV-1 to suppression by CTL. Taken together, these
      data demonstrate the functionality of Nef to down-regulate MHC-I in vivo during
      stable chronic infection, and suggest that this function is maintained by the
      need of HIV-1 to cope with the antiviral CTL response.

PMID- 18322218
TI  - Activation of human NK cells by the bacterial pathogen-associated molecular
      pattern muramyl dipeptide.
AB  - Muramyl dipeptide (MDP) is a bacterial pathogen associated molecular pattern
      derived from both Gram-positive and -negative bacteria. It is a specific ligand
      for nuclear oligomerization domain 2, a pattern recognition receptor best
      characterized for its role in immunosurveillance in the gut. In this study, we
      demonstrate that human peripheral blood NK cells express nuclear oligomerization
      domain 2 and respond to MDP. NK cells naturally internalize MDP leading to direct
      cell activation, including signaling through NFkappaB: characterized by p50/p65
      heterodimers at early stimulations times and sustained activation of p50
      homodimers. Moreover, MDP synergizes with IFN-alpha and IL-12 to activate NK
      cells and stimulate IFN-gamma secretion, suggesting a role for accessory cells in
      induction of an optimal NK cell response. Although IL-12 costimulation leads to a
      greater IFN-gamma response by NK cells, higher levels of CD69 in response to MDP
      are induced in the presence of IFN-alpha, suggesting that different pathogen
      induced cytokine profiles will affect downstream NK cell responses. In contrast,
      MDP alone or in combination with either IFN-alpha or IL-12 only poorly increases
      NK cell cytotoxicity. In summary, this report identifies MDP as a bacterial
      pathogen associated molecular pattern that activates human NK cells.

PMID- 18322219
TI  - IL-10 and TGF-beta control the establishment of persistent and transmissible
      infections produced by Leishmania tropica in C57BL/6 mice.
AB  - Leishmania tropica is the causative agent of Old World anthroponotic cutaneous
      leishmaniasis, which is characterized by lesions that take an extended period of
      time to heal, often resulting in disfiguring scars, and are more refractory to
      treatment than leishmaniasis caused by Leishmania major. Immunologic studies
      involving experimental animal models of L. tropica infection are virtually
      nonexistent. In the current study, infectious-stage L. tropica were used to
      establish dermal infections in C57BL/6 and BALB/c mice. In both strains, the
      lesions were slow to develop and showed minimal pathology. They nonetheless
      contained a stable number of between 10(4) and 10(5) parasites for over 1 year,
      which were efficiently picked up by a natural sand fly vector, Phlebotomus
      sergenti. Control of parasite growth depended on the development of a Th1
      response, as C57BL/6 mice genetically deficient in Th1 cytokines and BALB/c mice
      treated with Abs to IFN-gamma harbored significantly more parasites. By contrast,
      IL-10-deficient mice harbored significantly fewer parasites throughout the
      infection. To further study the immunologic mechanisms that may prevent efficient
      clearance of the parasites, IL-10 and TGF-beta signaling were abrogated during
      the chronic phase of infection in wild-type C57BL/6 mice. Distinct from chronic
      L. major infection, IL-10 blockade alone had no effect on L. tropica, but
      required simultaneous treatment with anti-TGF-beta Abs to promote efficient
      parasite clearance from the infection site. Thus, chronic infection with L.
      tropica appears to be established via multiple suppressive factors, which
      together maintain the host as a long-term reservoir of infection for vector sand
      flies.

PMID- 18322220
TI  - Characterization of pulmonary T cell response to helper-dependent adenoviral
      vectors following intranasal delivery.
AB  - In spite of the extensive research in the field of gene therapy, host immune
      responses continue to be the major barrier in translating basic research to
      clinical practice. Helper-dependent adenoviral (HD-Ad) vectors show great
      potential for pulmonary gene therapy, but the knowledge of pulmonary immune
      responses toward these vectors is very limited. In this study, we show that HD-Ad
      vectors are potent stimulators of dendritic cell (DC) maturation, thus leading to
      stimulation of T cell proliferation with approximately 6% of naive CD4(+) T cells
      from pulmonary mediastinal lymph node responding to HD-Ad-treated DCs. In
      contrast to the belief that HD-Ad vectors are unable to prime adaptive immune
      response, we show for the first time, through in vivo pulmonary studies in mice,
      that HD-Ad vectors can prime CD4(+) and CD8(+) T cell responses in the lung at
      high and substantially low doses. This indicates cross-presentation of HD-Ad
      derived epitopes by DCs to prime CD8(+) T cell responses. To assess the basis of
      pulmonary T cell response against HD-Ad vectors, we examined the response of
      conventional DCs (cDCs) and plasmacytoid DCs (pDCs) in the lung. In response to
      HD-Ad delivery, there is induction of maturation in both cDC and pDC subsets, but
      it is the cDCs, not pDCs, that migrate rapidly to draining lymph nodes within the
      first 2 days after vector delivery to prime adaptive immune response against
      these vectors. These findings have implications for development of strategies to
      prevent adaptive immune responses against gene therapy vectors.

PMID- 18322222
TI  - IFN-beta increases listeriolysin O-induced membrane permeabilization and death of
      macrophages.
AB  - Type I IFN (IFN-I) signaling is detrimental to cells and mice infected with
      Listeria monocytogenes. In this study, we investigate the impact of IFN-I on the
      activity of listeriolysin O (LLO), a pore-forming toxin and virulence protein
      released by L. monocytogenes. Treatment of macrophages with IFN-beta increased
      the ability of sublytic LLO concentrations to cause transient permeability of the
      plasma membrane. At higher LLO concentrations, IFN-beta enhanced the complete
      breakdown of membrane integrity and cell death. This activity of IFN-beta
      required Stat1. Perturbation of the plasma membrane by LLO resulted in activation
      of the p38MAPK pathway. IFN-beta pretreatment enhanced LLO-mediated signaling
      through this pathway, consistent with its ability to increase membrane damage.
      p38MAPK activation in response to LLO was independent of TLR4, a putative LLO
      receptor, and inhibition of p38MAPK neither enhanced nor prevented LLO-induced
      death. IFN-beta caused cells to express increased amounts of caspase 1 and to
      produce a detectable caspase 1 cleavage product after LLO treatment. Contrasting
      recent reports with another pore-forming toxin, this pathway did not aid cell
      survival as caspase 1-deficient cells were equally sensitive to lysis by LLO. Key
      lipogenesis enzymes were suppressed in IFN-beta-treated cells, which may
      exacerbate the membrane damage caused by LLO.

PMID- 18322221
TI  - Deviation from a strong Th1-dominated to a modest Th17-dominated CD4 T cell
      response in the absence of IL-12p40 and type I IFNs sustains protective CD8 T
      cells.
AB  - The differentiation of naive CD4 T cells into specific effector subsets is
      controlled in large part by the milieu of cytokines present during their initial
      encounter with Ag. Cytokines that drive differentiation of the newly described
      Th17 lineage have been characterized in vitro, but the cytokines that prime
      commitment to this lineage in response to infection in vivo are less clear.
      Listeria monocytogenes (Lm) induces a strong Th1 response in wild-type mice. By
      contrast, we demonstrate that in the absence of IL-12p40 (or IFN-gamma) and type
      I IFN receptor signaling, the Th1 Ag-specific CD4 T cell response is virtually
      abolished and replaced by a relatively low magnitude Th17-dominated response.
      This Th17 response was dependent on TGF-beta and IL-6. Despite this change in CD4
      T cell response, neither the kinetics of the CD4 and CD8 T cell responses, the
      quality of the CD8 T cell response, nor the ability of CD8 T cells to mediate
      protection were affected. Thus, generation of protective CD8 T cell immunity was
      resilient to perturbations that replace a strong Th1-dominated to a reduced
      magnitude Th17-dominated Ag-specific CD4 T cell response.

PMID- 18322223
TI  - Mannose-binding lectin (MBL) facilitates opsonophagocytosis of yeasts but not of
      bacteria despite MBL binding.
AB  - Mannose-binding lectin (MBL) is a serum protein of the innate immune system.
      After binding to a microorganism, MBL in complex with MBL-associated serine
      proteases activates the complement system, resulting in cleavage of complement
      factor C3. Cleaved C3 on the surface of the microorganism mediates opsonization
      for clearance, but the impact of MBL on subsequent phagocytosis has not been
      widely studied. We investigated the role of MBL in complement activation and
      phagocytosis of various bacteria and yeast species by flow cytometry. We measured
      both the C3 deposition during serum opsonization of fluorescent-labeled
      microorganisms as well as subsequent uptake of these microorganisms by human
      neutrophils. In MBL-deficient sera, a consistently decreased C3 deposition on
      both zymosan and Candida albicans was found and a reduced phagocytosis by
      neutrophils that was restored by exogenous MBL. This indicates that the lectin
      pathway of complement activation is important for the opsonophagocytosis of
      yeasts. In contrast, the C1q-dependent classical pathway dominated in the
      opsonization and phagocytosis of Staphylococcus aureus, Streptococcus pneumoniae,
      and Escherichia coli, whereas no effect of MBL was found. Both the lectin and the
      classical pathway of complement activation were highly amplified by the
      alternative route for opsonophagocytosis by neutrophils of yeast as well as
      microbial species. In summary, our data demonstrate that yeast species are
      preferentially opsonized and subsequently phagocytosed via activation of the
      lectin pathway of complement, whereas the uptake of bacterial strains was found
      to be largely MBL independent.

PMID- 18322224
TI  - Role of polymorphonuclear neutrophils on infectious complications stemming from
      Enterococcus faecalis oral infection in thermally injured mice.
AB  - Thermally injured mice are susceptible to Enterococcus faecalis translocation. In
      this study, the role of polymorphonuclear neutrophils (PMN) on the development of
      sepsis stemming from E. faecalis translocation was studied in SCID-beige (SCIDbg)
      mice depleted of PMN (SCIDbgN mice) or macrophages (Mphi) and PMN (SCIDbgMN
      mice). Sepsis was not developed in SCIDbgN mice orally infected with E. faecalis,
      while the orally infected pathogen spread systemically in the same mice
      inoculated with PMN from thermally injured mice (TI-PMN). SCIDbgMN mice were
      shown to be greatly susceptible to sepsis caused by E. faecalis translocation,
      while orally infected E. faecalis did not spread into sepsis in the same mice
      that were previously inoculated with Mphi from unburned SCIDbg mice (resident
      Mphi). In contrast, orally infected E. faecalis spread systemically in SCIDbgMN
      mice inoculated with resident Mphi and TI-PMN, while all SCIDbgMN mice inoculated
      in combination with resident Mphi and PMN from unburned SCIDbg mice survived
      after the infection. After cultivation with TI-PMN in a dual-chamber transwell,
      resident Mphi converted to alternatively activated Mphi, which are inhibitory on
      the generation of classically activated Mphi (typical effector cells in host
      antibacterial innate immunities). TI-PMN were characterized as immunosuppressive
      PMN (PMN-II) with abilities to produce cc-chemokine ligand-2 and IL-10. These
      results indicate that PMN-II appearing in response to burn injury impair host
      antibacterial resistance against sepsis stemming from E. faecalis translocation
      through the conversion of resident Mphi to alternatively activated Mphi.

PMID- 18322225
TI  - Anthrax lethal toxin increases superoxide production in murine neutrophils via
      differential effects on MAPK signaling pathways.
AB  - The combination of lethal factor and its receptor-binding partner, protective Ag,
      is termed lethal toxin (LT) and has critical pathogenic activity during infection
      with Bacillus anthracis. We herein report that anthrax LT binds and enters murine
      neutrophils, leading to the cleavage of mitogen-activated protein kinase
      kinase/MEK/MAPKK 1-4 and 6, but not mitogen-activated protein kinase kinase 5 and
      7. Anthrax LT treatment of neutrophils disrupts signaling to downstream MAPK
      targets in response to TLR stimulation. Following anthrax LT treatment, ERK
      family and p38 phosphorylation are nearly completely blocked, but signaling to
      JNK family members persists in vitro and ex vivo. In contrast to previous reports
      involving human neutrophils, anthrax LT treatment of murine neutrophils increases
      their production of superoxide in response to PMA or TLR stimulation in vitro or
      ex vivo. Although this enhanced superoxide production correlates with effects due
      to the LT-induced blockade of ERK signaling, it requires JNK signaling that
      remains largely intact despite the activity of anthrax LT. These findings reveal
      a previously unrecognized mechanism through which anthrax LT supports a critical
      proinflammatory response of murine neutrophils.

PMID- 18322226
TI  - Endogenous IFN-gamma production is induced and required for protective immunity
      against pulmonary chlamydial infection in neonatal mice.
AB  - Chlamydia trachomatis infection in neonates, not adults, has been associated with
      the development of chronic respiratory sequelae. Adult chlamydial infections
      induce Th1-type responses that subsequently clear the infection, whereas the
      neonatal immune milieu in general has been reported to be biased toward Th2-type
      responses. We examined the protective immune responses against intranasal
      Chlamydia muridarum challenge in 1-day-old C57BL/6 and BALB/c mice. Infected
      C57BL/6 pups displayed earlier chlamydial clearance (day 14) compared with BALB/c
      pups (day 21). However, challenged C57BL/6 pups exhibited prolonged deficits in
      body weight gain (days 12-30) compared with BALB/c pups (days 9-12), which
      correlated with continual pulmonary cellular infiltration. Both strains exhibited
      a robust Th1-type response, including elevated titers of serum antichlamydial
      IgG2a and IgG2b, not IgG1, and elevated levels of splenic C. muridarum-specific
      IFN-gamma, not IL-4, production. Additionally, elevated IFN-gamma, not IL-4
      expression, was observed locally in the infected lungs of both mouse strains. The
      immune responses in C57BL/6 pups were significantly greater compared with BALB/c
      pups after chlamydial challenge. Importantly, infected mice deficient in IFN
      gamma or IFN-gamma receptor demonstrated enhanced chlamydial dissemination, and
      100% of animals died by 2 wk postchallenge. Collectively, these results indicate
      that neonatal pulmonary chlamydial infection induces a robust Th1-type response,
      with elevated pulmonary IFN-gamma production, and that endogenous IFN-gamma is
      important in protection against this infection. The enhanced IFN-gamma induction
      in the immature neonatal lung also may be relevant to the development of
      respiratory sequelae in adult life.

PMID- 18322227
TI  - Spleen size predicts resistance of rainbow trout to Flavobacterium psychrophilum
      challenge.
AB  - Selective breeding of animals for increased innate resistance offers an
      attractive strategy to control disease in agriculture. However, this approach is
      limited by an incomplete knowledge of the heritability, duration, and
      mechanism(s) of resistance, as well as the impact of selection on the immune
      response to unrelated pathogens. Herein, as part of a rainbow trout broodstock
      improvement program, we evaluated factors involved in resistance against a
      bacterial disease agent, Flavobacterium psychrophilum. In 2005, 71 full-sibling
      crosses, weighing an average of 2.4 g, were screened, and resistant and
      susceptible crosses were identified. Naive cohorts were evaluated at 10 and 800 g
      in size, and most maintained their original relative resistant or susceptible
      phenotypes, indicating that these traits were stable as size increased >300-fold.
      During the course of these studies, we observed that the normalized spleen
      weights of the resistant fish crosses were greater than those of the susceptible
      fish crosses. To test for direct association, we determined the spleen-somatic
      index of 103 fish crosses; created high, medium, and low spleen-index groups; and
      determined survival following challenge with F. psychrophilum or Yersinia
      ruckeri. Consistent with our previous observations, trout with larger spleen
      indices were significantly more resistant to F. psychrophilum challenge; however,
      this result was pathogen-specific, as there was no correlation of spleen size
      with survival following Y. ruckeri challenge. To our knowledge, this is the first
      report of a positive association between spleen size and disease resistance in a
      teleost fish. Further evaluation of spleen index as an indirect measure of
      disease resistance is warranted.

PMID- 18322228
TI  - ERK5/BMK1 is indispensable for optimal colony-stimulating factor 1 (CSF-1)
      induced proliferation in macrophages in a Src-dependent fashion.
AB  - CSF-1, by binding to its high-affinity receptor CSF-1R, sustains the survival and
      proliferation of monocyte/macrophages, which are central cells of innate immunity
      and inflammation. The MAPK ERK5 (also known as big MAPK-1, BMK1, or MAPK7) is a
      98-kDa molecule sharing high homology with ERK1/2. ERK5 is activated by oxidative
      stress or growth factor stimulation. This study was undertaken to characterize
      ERK5 involvement in macrophage signaling that is elicited by CSF-1. Exposure to
      the CSF-1 of primary human macrophages or murine macrophage cell lines, as well
      as murine fibroblasts expressing ectopic CSF-1R, resulted in a rapid and
      sustained increase of ERK5 phosphorylation on activation-specific residues. In
      the BAC1.2F5 macrophage cell line, ERK5 was also activated by another mitogen, GM
      CSF, while macrophage activators such as LPS or IFN-gamma and a number of
      nonproliferative cytokines failed. Src family kinases were found to link the
      activation of CSF-1R to that of ERK5, whereas protein kinase C or the serine
      phosphatases PP1 and PP2A seem not to be involved in the process. Treatment of
      macrophages with ERK5-specific small interfering RNA markedly reduced CSF-1
      induced DNA synthesis and total c-Jun phosphorylation and expression, while
      increasing the expression of the cyclin-dependent kinase inhibitor p27. Following
      CSF-1 treatment, the active form of ERK5 rapidly translocated from cytosol to
      nucleus. Taken together, the results reported in this study show that ERK5 is
      indispensable for optimal CSF-1-induced proliferation and indicate a novel target
      for its control.

PMID- 18322229
TI  - Adenosine promotes IL-6 release in airway epithelia.
AB  - In the airway epithelia, extracellular adenosine modulates a number of biological
      processes. However, little is known about adenosine's role in the inflammatory
      responses of airway epithelial cells. Recent studies suggest that the chronic
      elevation of extracellular adenosine in mice leads to pulmonary inflammation and
      fibrosis. Yet, the underlying molecular mechanism has not been well understood
      and little attention has been paid to the role of airway epithelia in adenosine
      triggered inflammation. In the present work, we examined the role of adenosine in
      releasing IL-6 from airway epithelia. In Calu-3 human airway epithelial cells,
      apical but not basolateral adenosine elicited robust, apically polarized release
      of IL-6, along with proinflammatory IL-8. Both protein kinase A and protein
      kinase C mediated the adenosine-induced IL-6 release, at least partly via
      phosphorylation of CREB. Protein kinase C appeared to phosphorylate CREB through
      activating ERK. In addition, A2A but not A2B adenosine receptors were
      specifically required for the adenosine-induced IL-6 release. Furthermore, in rat
      bronchoalveolar lavage fluid, adenosine triggered the release of IL-6 as well as
      proinflammatory IL-1beta. Adenosine also mediated the release of a considerable
      portion of the LPS-induced IL-6 in rat bronchoalveolar lavage fluid. Our findings
      provide a possible molecular link between extracellular adenosine elevation and
      lung inflammation and fibrosis.

PMID- 18322230
TI  - Cross-talk between ICAM-1 and granulocyte-macrophage colony-stimulating factor
      receptor signaling modulates eosinophil survival and activation.
AB  - Reversal of eosinophilic inflammation has been an elusive therapeutic goal in the
      management of asthma pathogenesis. In this regard, GM-CSF is a primary candidate
      cytokine regulating eosinophil activation and survival in the lung; however, its
      molecular mechanism of propagation and maintenance of stimulated eosinophil
      activation is not well understood. In this study, we elucidate those late
      interactions occurring between the GM-CSF receptor and activated eosinophil
      signaling molecules. Using coimmunoprecipitation with GM-CSF-stimulated
      eosinophils, we have identified that the GM-CSF receptor beta-chain (GMRbeta)
      interacted with ICAM-1 and Shp2 phosphatase, as well as Slp76 and ADAP adaptor
      proteins. Separate experiments using affinity binding with a tyrosine
      phosphorylated peptide containing an ITIM (ICAM-1 residues 480-488) showed
      binding to Shp2 phosphatase and GMRbeta. However, the interaction of GMRbeta with
      the phosphorylated ICAM-1-derived peptide was observed only with stimulated
      eosinophil lysates, suggesting that the interaction of GMRbeta with ICAM-1
      required phosphorylated Shp2 and/or phosphorylated GMRbeta. Importantly, we found
      that inhibition of ICAM-1 in activated eosinophils blocked GM-CSF-induced
      expression of c-fos, c-myc, IL-8, and TNF-alpha. Moreover, inhibition of ICAM-1
      expression with either antisense oligonucleotide or an ICAM-1-blocking Ab
      effectively inhibited ERK activation and eosinophil survival. We concluded that
      the interaction between ICAM-1 and the GM-CSF receptor was essential for GM-CSF
      induced eosinophil activation and survival. Taken together, these results provide
      novel mechanistic insights defining the interaction between ICAM-1 and the GM-CSF
      receptor and highlight the importance of targeting ICAM-1 and GM-CSF/IL-5/IL-3
      receptor systems as a therapeutic strategy to counter eosinophilia in asthma.

PMID- 18322231
TI  - Dual modulation of airway smooth muscle contraction by Th2 cytokines via matrix
      metalloproteinase-1 production.
AB  - Altered contractility of airway smooth muscle (SM) is one of the main causes of
      allergic asthma, in which the predominance of Th2 over Th1 cytokines plays a
      central role. In the present study, we examine the effects of Th2 cytokines on
      airway SM contraction. Treatment with a low concentration of IL-4 (0.2 ng/ml) for
      6 h augmented, whereas higher concentrations (2-20 ng/ml) inhibited, agonist
      induced contractions of collagen gels containing bovine tracheal SM cells.
      Another Th2 cytokine (IL-13) showed an augmentation of gel contraction in the
      concentration range of 20-200 ng/ml. IL-4 and IL-13 increased mRNA expression and
      protein secretion of matrix metalloproteinase (MMP)-1, but these cytokines did
      not affect Ca(2+)-mobilizing properties and phosphorylation levels of myosin L
      chain in bovine tracheal SM cells. These changes were sensitive to wortmannin, an
      inhibitor of PI3K, but not to leflunomide, an inhibitor of STAT6. Scanning
      electron microscope observation revealed that collagen fibers twining around SM
      cells were completely dissolved in 20 ng/ml IL-4-treated gels and reorganized
      into basket-like structure in 20 ng/ml IL-13-treated gels. Exogenous application
      of high and low concentrations of MMP-1 also induced the inhibition and
      augmentation of gel contraction, respectively. Furthermore, nonselective MMP
      inhibitor galardin suppressed the effects of IL-4 and IL-13 on gel contraction,
      and MMP-1-targeted small-interfering RNA reversed the inhibitory effects of IL-4
      on gel contraction to the augmentation. This indicates that Th2 cytokines
      modulate airway contraction without affecting cellular contractility but by
      secreting MMP-1 from the SM cells via PI3K activation and changing cell-to-matrix
      interactions.

PMID- 18322232
TI  - STAT-1 signaling in human lung fibroblasts is induced by vanadium pentoxide
      through an IFN-beta autocrine loop.
AB  - The inhalation of vanadium pentoxide (V(2)O(5)) results in bronchitis and airway
      fibrosis. The lung fibrotic response to V(2)O(5) partially resolves where
      fibroblasts first proliferate and deposit collagen, but then undergo growth
      arrest and apoptosis. STAT-1 mediates fibroblast growth arrest and apoptosis. We
      previously reported that STAT-1 is a protective factor and mice lacking STAT-1
      are more susceptible to lung fibrosis. We also reported that V(2)O(5)-induced
      STAT-1 phosphorylation in lung fibroblasts requires H(2)O(2) and de novo protein
      synthesis. In this study, we identified IFN-beta as the protein that mediates
      STAT-1 activation by V(2)O(5) in normal human lung fibroblasts and identified
      NADPH and xanthine oxidase systems as sources of H(2)O(2) that drive IFN-beta
      gene expression. STAT-1 phosphorylation was decreased with neutralizing Abs to
      IFN-beta as well as an inhibitor of JAK. V(2)O(5) also increased transcription of
      an IFN-inducible and STAT-1-dependent chemokine, CXCL10. Inhibition of H(2)O(2)
      generating enzyme systems NADPH oxidase by apocynin and xanthine oxidase by
      allopurinol individually reduced STAT-1 phosphorylation. Apocynin and allopurinol
      also decreased V(2)O(5)-induced IFN-beta mRNA levels and CXCL10 expression. IFN
      alpha transcription was inhibited only by allopurinol. Taken together, these data
      indicate that fibroblasts play a role in the innate immune response to vanadium
      induced oxidative stress by synthesizing IFN-beta and activating STAT-1 to cause
      growth arrest and increase levels of CXCL10, a potent antifibrotic factor. This
      mechanism is postulated to counterbalance profibrogenic mechanisms that follow
      V(2)O(5) injury.

PMID- 18322233
TI  - Induced loss of Syk in human basophils by non-IgE-dependent stimuli.
AB  - In the general population, Syk expression in human basophils is highly variable
      and correlates well with the IgE-mediated responsiveness of these cells. Previous
      studies established that IgE-mediated stimulation results in loss of Syk
      expression. The current studies investigated whether stimulation through other
      receptors results in loss of Syk. Two classes of stimulation were examined, those
      that operate through the kinase Syk and those that operate through a GTP-binding
      protein. These studies demonstrated that aggregation of leukocyte Ig-like
      receptor LILRA-2 resulted in phosphorylation of Syk and c-Cbl, was inhibited by a
      third generation Syk inhibitor with an expected IC(50), and induced histamine
      release in strict proportion to release induced by anti-IgE Ab. Stimulation of
      LILRA-2 for 18 h resulted in modest loss of Syk that correlated with the more
      profound loss of Syk induced by anti-IgE Ab. Human recombinant histamine
      releasing factor has also recently been shown to induce Syk phosphorylation and
      in the current studies has also been shown to induce loss of Syk in 18-h
      cultures. fMLP stimulation for 18 h was also found to induce modest loss of Syk.
      fMLP induced phosphorylation of c-Cbl that was sustained for at least 45 min.
      Phosphorylation of c-Cbl was inhibited by a Syk kinase inhibitor but with an
      IC(50) that was not consistent with Syk activity, suggesting another kinase was
      responsible for Cbl phosphorylation following fMLP. These studies demonstrate
      that it is possible to induce the loss of Syk expression in human basophils by a
      non-IgE-dependent mechanism and even by a mechanism that does directly involve
      Syk in the reaction complex.

PMID- 18322235
TI  - Neuritogenic effects of T cell-derived IL-3 on mouse splenic sympathetic neurons
      in vivo.
AB  - To determine the role played by lymphocytes and cytokines in the growth of
      sympathetic neurons in vivo, the innervation and cytokine levels were examined in
      the spleens of SCID mice that lack T and B cells. Splenic noradrenaline, nerve
      growth factor (NGF), and IL-1beta levels were elevated in SCID mice.
      Immunohistochemical examination revealed that the density of tyrosine hydroxylase
      positive (TH(+)) fibers of splenic central arteries in SCID mice was increased
      compared with wild-type C.B-17 mice, while SCID mice had significantly fewer
      TH(+) fibers in their periarteriolar lymphatic sheaths (PALS). Two weeks after
      SCID mice were injected with C.B-17 splenic T cells, their TH(+) fiber staining
      increased in the PALS. IL-3 levels increased significantly in SCID mice following
      T cell reconstitution, and the administration of anti-IL-3 Ab blocked the above T
      cell-induced increase in innervation in the PALS. Anti-IL-3 treatment also
      inhibited the regeneration of splenic sympathetic neurons in C.B-17 mice after
      they were chemically sympathetomized with 6-hydroxydopamine. Depletion of NK
      cells by anti-asialo GM1 promoted the splenic innervation in SCID mice, while
      there were no significant changes in the innervation between CD8(+) T cell
      deficient beta(2)-microglobulin knockout mice and their wild type. Our results
      suggest that T cells (probably CD4(+) Th cells but not CD8(+) CTLs) play a role
      in regulating the sympathetic innervation of the spleen; this effect appeared to
      be mediated, at least in part, by IL-3. On the contrary, NK cells may exert an
      inhibitory effect on the sympathetic innervation.

PMID- 18322234
TI  - Genetic analysis of the role of the PI3K-Akt pathway in lipopolysaccharide
      induced cytokine and tissue factor gene expression in monocytes/macrophages.
AB  - LPS stimulation of monocytes/macrophages induces the expression of genes encoding
      proinflammatory cytokines and the procoagulant protein, tissue factor. Induction
      of these genes is mediated by various signaling pathways, including mitogen
      activated protein kinases, and several transcription factors, including Egr-1, AP
      1, ATF-2, and NF-kappaB. We used a genetic approach to determine the role of the
      phosphatidylinositol-3-kinase (PI3K)-protein kinase B (Akt) pathway in the
      regulation of LPS signaling and gene expression in isolated macrophages and in
      mice. The PI3K-Akt pathway is negatively regulated by the phosphatase and tensin
      homologue (PTEN). We used peritoneal exudate cells from Pik3r1-deficient mice,
      which lack the p85alpha regulatory subunit of PI3K and have reduced PI3K
      activity, and peritoneal macrophages from PTEN(flox/flox)/LysMCre mice (PTEN(-/
      )), which have increased Akt activity. Analysis of LPS signaling in Pik3r1(-/-)
      and PTEN(-/-) cells indicated that the PI3K-Akt pathway inhibited activation of
      the ERK1/2, JNK1/2, and p38 mitogen-activated protein kinases and reduced the
      levels of nuclear Egr-1 protein and phosphorylated ATF-2. Modulating the PI3K-Akt
      pathway did not affect LPS-induced degradation of IkappaBalpha or NF-kappaB
      nuclear translocation. LPS induction of TNF-alpha, IL-6, and tissue factor gene
      expression was increased in Pik3r1(-/-) peritoneal exudate cells and decreased in
      PTEN(-/-) peritoneal macrophages compared with wild-type (WT) cells. Furthermore,
      LPS-induced inflammation and coagulation were enhanced in WT mice containing
      Pik3r1(-/-) bone marrow compared with WT mice containing WT bone marrow and in
      mice lacking the p85alpha subunit in all cells. Taken together, our results
      indicate that the PI3K-Akt pathway negatively regulates LPS signaling and gene
      expression in monocytes/macrophages.

PMID- 18322236
TI  - CD44 suppresses TLR-mediated inflammation.
AB  - The cell adhesion molecule CD44, which is the major hyaluronan receptor, has been
      implicated in the binding, endocytosis, and metabolism of hyaluronan. Previous
      studies have revealed that CD44 plays crucial roles in a variety of inflammatory
      diseases. In recent years, TLRs, which are ancient microbial pattern recognition
      receptors, have been shown to initiate an innate immune response and have been
      linked to a variety of inflammatory diseases. The present study shows that CD44
      negatively regulates in vivo inflammation mediated by TLRs via NF-kappaB
      activation, which leads to proinflammatory cytokine production. Furthermore, our
      results show that CD44 directly associates with TLR2 when stimulated by the TLR2
      ligand zymosan and that the cytoplasmic domain of CD44 is crucial for its
      regulatory effect on TLR signaling. This study indicates that CD44 plays a
      protective role in TLR-mediated inflammation and is the first to demonstrate a
      direct association between CD44 and a TLR.

PMID- 18322237
TI  - Control of IFN-alphaA by CD73: implications for mucosal inflammation.
AB  - Inflammatory diseases influence tissue metabolism, altering regulation of
      extracellular adenine nucleotides, with a resultant protective influence of
      adenosine. Ecto-5'-nucleotidase (CD73) is a central surface enzyme generating
      extracellular adenosine. Thus, we hypothesized that CD73 is protective in mucosal
      inflammation as modeled by trinitrobenzene sulfonate (TNBS) colitis. Initial
      studies revealed a >3-fold induction of CD73 mRNA levels after TNBS colitis.
      Additionally, the severity of colitis was increased, as determined by weight loss
      and colonic shortening, in cd73(-/-) mice relative to cd73(+/+) controls.
      Likewise, enteral administration of the selective CD73 inhibitor alpha,beta
      methylene ADP to cd73(+/+) mice resulted in a similar increase in severity of
      TNBS colitis. Gene array profiling of cytokine mRNA expression, verified by real
      time PCR, revealed a >90% down-regulation of IFN-alphaA in cd73(-/-) mice and
      alpha,beta-methylene ADP-treated cd73(+/+) mice, compared with cd73(+/+) mice.
      Exogenous administration of recombinant IFN-alphaA partially protected TNBS
      treated cd73(-/-) mice. Cytokine profiling revealed similar increases in both IFN
      gamma and TNF-alpha mRNA in colitic animals, independent of genotype. However, IL
      10 mRNA increased in wild-type mice on day 3 after TNBS administration, whereas
      cd73(-/-) mice mounted no IL-10 response. This IL-10 response was restored in the
      cd73(-/-) mice by exogenous IFN-alphaA. Further cytokine profiling revealed that
      this IL-10 induction is preceded by a transient IFN-alphaA induction on day 2
      after TNBS exposure. Together, these studies indicate a critical regulatory role
      for CD73-modulated IFNalphaA in the acute inflammatory phase of TNBS colitis,
      thereby implicating IFN-alphaA as a protective element of adenosine signaling
      during mucosal inflammation.

PMID- 18322238
TI  - A phosphosite screen identifies autocrine TGF-beta-driven activation of protein
      kinase R as a survival-limiting factor for eosinophils.
AB  - The differential usage of signaling pathways by chemokines and cytokines in
      eosinophils is largely unresolved. In this study, we investigate signaling
      similarities and differences between CCL11 (eotaxin) and IL-5 in a phosphosite
      screen of human eosinophils. We confirm many previously known pathways of
      cytokine and chemokine signaling and elucidate novel phosphoregulation in
      eosinophils. The signaling molecules that were stimulated by both agents were
      members of the ERK1/2 and p38 MAPK pathways and their downstream effectors such
      as RSK and MSK1/2. Both agents inhibited S6 kinase, protein kinase Cepsilon, and
      glycogen synthase kinase 3 alpha and beta. The molecules that were differentially
      regulated include STATs and protein kinase R (PKR). One of the chief findings in
      this investigation was that PKR and eukaryotic initiation factor 2alpha are
      phosphorylated under basal conditions in eosinophils and neutrophils. This basal
      phosphorylation was linked to autocrine secretion of TGF-beta in eosinophils. TGF
      beta directly activates PKR in eosinophils. Basal phosphorylation of PKR was
      inhibited by incubation of eosinophils with a neutralizing anti-TGF-beta Ab
      suggesting its physiological importance. We show that inhibition of PKR activity
      prolongs eosinophil survival. The eosinophil survival factor IL-5 strongly
      suppresses phosphorylation of PKR. The biological relevance of IL-5 inhibition of
      phospho-PKR was established by the observation that ex vivo bone marrow-derived
      eosinophils from OVA-immunized mice had no PKR phosphorylation in contrast to the
      high level of phosphorylation in sham-immunized mice. Together, our findings
      suggest that survival of eosinophils is in part controlled by basal activation of
      PKR through autocrine TGF-beta and that this could be modulated by a Th2
      microenvironment in vivo.

PMID- 18322239
TI  - A helminth immunomodulator reduces allergic and inflammatory responses by
      induction of IL-10-producing macrophages.
AB  - The coincidence between infections with parasitic worms and the reduced
      prevalence of allergic disease in humans and in animal models has prompted the
      search for helminth molecules with antiallergic and antiinflammatory potential.
      We report herein that filarial cystatin, a secreted protease inhibitor of
      filarial nematodes, suppresses Th2-related inflammation and the ensuing asthmatic
      disease in a murine model of OVA-induced allergic airway responsiveness.
      Treatment with recombinant filarial cystatin inhibited eosinophil recruitment,
      reduced levels of OVA-specific and total IgE, down-regulated IL-4 production, and
      suppressed allergic airway hyperreactivity when applied during or after
      sensitization and before challenge with the allergen. Depletion of macrophages by
      clodronate-containing liposomes prevented the curative effects and restored the
      levels of infiltrating cells, IgE, and allergic airway reactivity. Blocking of IL
      10 by application of anti-IL-10 receptor Abs restored the reduced number of
      infiltrating cells and the levels of OVA-specific IgE. In contrast, depletion of
      regulatory T cells by anti-CD25 Abs had only limited effects. Cystatin also
      modulated macrophage-mediated inflammation in a murine model of dextran sulfate
      sodium-induced colitis, leading to reduction of inflammatory infiltrations and
      epithelial damage. Our data demonstrate that treatment with a single helminth
      protein can exert the antiallergic effects of helminth infections.

PMID- 18322240
TI  - A critical role for ABCG1 in macrophage inflammation and lung homeostasis.
AB  - ATP-binding cassette transporter G1 (ABCG1) effluxes cholesterol from macrophages
      and plays an important role in pulmonary lipid homeostasis. We hypothesize that
      macrophages from Abcg1(-/-) mice have increased inflammatory activity, thereby
      promoting acceleration of pulmonary disease. We herein demonstrate increased
      numbers of inflammatory cytokines and infiltrating neutrophils, eosinophils,
      dendritic cells, T cells, and B cells into lungs of Abcg1(-/-) mice before the
      onset of severe lipidosis. We further investigated the role of macrophages in
      causing pulmonary disease by performing bone marrow transplantations using B6 and
      Abcg1(-/-) bone marrow. We found that it was the macrophage, and not pneumocyte
      type II cells or other nonhematopoietic cells in the lung, that appeared to be
      the primary cell type involved in the onset of both pulmonary lipidosis and
      inflammation in the Abcg1(-/-) mice. Additionally, our results demonstrate that
      Abcg1(-/-) macrophages had elevated proinflammatory cytokine production,
      increased apoptotic cell clearance, and were themselves more prone to apoptosis
      and necrosis. However, they were quickly repopulated by monocytes that were
      recruited to Abcg1(-/-) lungs. In conclusion, we have shown that ABCG1 deletion
      in macrophages causes a striking inflammatory phenotype and initiates onset of
      pulmonary lipidosis in mice. Thus, our studies reveal a critical role for
      macrophage ABCG1 in lung inflammation and homeostasis.

PMID- 18322241
TI  - Protective roles of the fractalkine/CX3CL1-CX3CR1 interactions in alkali-induced
      corneal neovascularization through enhanced antiangiogenic factor expression.
AB  - Macrophages accumulate during the course of corneal neovascularization, but its
      mechanisms and roles still remain elusive. To address these points, we herein
      examined corneal neovascularization after alkali injury in mice deficient in
      fractalkine receptor/CX3CR1, which is normally expressed by macrophages. After
      alkali injury, the mRNA expression of CX3CR1 was augmented along with
      accumulation of F4/80-positive macrophages and Gr-1-positive neutrophils in the
      corneas. Compared with wild-type mice, CX3CR1-deficient mice exhibited enhanced
      corneal neovascularization 2 wk after injury, as evidenced by enlarged CD31
      positive areas. Concomitantly, the accumulation of F4/80-positive macrophages,
      but not Gr-1-positive neutrophils, was markedly attenuated in CX3CR1-deficient
      mice compared with wild-type mice. The intraocular mRNA expression of vascular
      endothelial growth factor (VEGF) was enhanced to similar extents in wild-type and
      CX3CR1-deifient mice after the injury. However, the mRNA expression of
      antiangiogenic factors, thrombospondin (TSP) 1, TSP-2, and a disintegrin and
      metalloprotease with thrombospondin (ADAMTS) 1, was enhanced to a greater extent
      in wild-type than CX3CR1-deificient mice. A double-color immunofluorescence
      analysis demonstrated that F4/80-positive cells also expressed CX3CR1 and ADAMTS
      1 and that TSP-1 and ADAMTS-1 were detected in CX3CR1-positive cells. CX3CL1
      enhanced TSP-1 and ADAMTS-1, but not VEGF, expression by peritoneal macrophages.
      Moreover, topical application of CX3CL1 inhibited corneal neovascularization at 2
      wk, along with enhanced intraocular expression of TSP-1 and ADAMTS-1 but not
      VEGF. Thus, these observations indicate that accumulation of CX3CR1-positive
      macrophages intraocularly can dampen alkali-induced corneal neovascularization by
      producing antiangiogenic factors such as TSP-1 and ADAMTS-1 and suggest the
      potential therapeutic efficacy of using CX3CL1 against alkali-induced corneal
      neovascularization.

PMID- 18322242
TI  - Delivery of biologically active anti-inflammatory cytokines IL-10 and IL-1ra in
      vivo by the Shigella type III secretion apparatus.
AB  - Pathogenicity of many Gram-negative bacteria relies on a type III secretion (T3S)
      apparatus, which is used for delivery of bacterial effectors into the host cell
      cytoplasm allowing the bacteria to manipulate host cell cytoskeleton network as
      well as to interfere with intracellular signaling pathways. In this study, we
      investigated the potential of the Shigella flexneri T3SA as an in vivo delivery
      system for biologically active molecules such as cytokines. The anti-inflammatory
      cytokines IL-10 and IL-1 receptor antagonist (IL-1ra) were genetically fused to
      the first 30 or 60 residues of the Shigella T3S effector IpaH9.8 or to the first
      50 residues of the Yersinia enterocolitica effector YopE and the recombinant
      fusion proteins were expressed in S. flexneri. YopE(50)-IL-10, IpaH(60)-IL-10,
      and IpaH(60)-IL-1ra were efficiently secreted via the T3S apparatus of Shigella.
      Moreover, these recombinant proteins did not impair the invasive ability of the
      bacteria in vitro. In a murine model, Shigella strains expressing YopE(50)-IL-10,
      IpaH(60)-IL-10, and IpaH(60)-IL-1ra induced a lower mortality in mice that was
      associated with reduced inflammation and a restricted localization of bacteria
      within the lung tissues as compared with wild-type Shigella. Moreover, the level
      of TNF-alpha and IL-1beta mRNA were reduced in the lungs following infection by
      IL-10- and IL-1ra-secreting Shigella, respectively. These findings demonstrate
      that the Shigella T3S apparatus can deliver biologically active cytokines in
      vivo, thus opening new avenues for the use of attenuated bacteria to deliver
      proteins for immunomodulation or gene therapy purposes.

PMID- 18322243
TI  - Hsp70 translocates into the plasma membrane after stress and is released into the
      extracellular environment in a membrane-associated form that activates
      macrophages.
AB  - Heat shock proteins (hsps) are intracellular chaperones that play a key role in
      the recovery from stress. Hsp70, the major stress-induced hsp, has been found in
      the extracellular medium and is capable of activating immune cells. The mechanism
      involved in Hsp70 release is controversial because this protein does not present
      a consensual secretory signal. In this study, we have shown that Hsp70 integrates
      into artificial lipid bilayer openings of ion conductance pathways. In addition,
      this protein was found inserted into the plasma membrane of cells after stress.
      Hsp70 was released into the extracellular environment in a membrane-associated
      form, sharing the characteristics of this protein in the plasma membrane.
      Extracellular membranes containing Hsp70 were at least 260-fold more effective
      than free recombinant protein in inducing TNF-alpha production as an indicator of
      macrophage activation. These observations suggest that Hsp70 translocates into
      the plasma membrane after stress and is released within membranous structures
      from intact cells, which could act as a danger signal to activate the immune
      system.

PMID- 18322244
TI  - Neutrophil chemokines KC and macrophage-inflammatory protein-2 are newly
      synthesized by tissue macrophages using distinct TLR signaling pathways.
AB  - Neutrophils are the first immune cells to migrate into infected tissue sites.
      Therefore an important step in the initiation of an immune response is the
      synthesis of the neutrophil-recruiting chemokines. In this in vivo study in mice,
      we show that resident tissue macrophages are the source of the major neutrophil
      chemoattractants, KC and MIP-2. Synthesis of these chemokines is rapidly
      regulated at the transcriptional level by signaling through TLR2, TLR3, and TLR4
      that have diverse specificities for pathogens. The major and alternative TLR
      signaling pathways are characterized by the adaptor proteins MyD88 or TRIF,
      respectively. KC and MIP-2 are both produced by signaling through MyD88. However
      MIP-2, but not KC, is also synthesized through the TRIF adaptor protein,
      identifying it as a new product of this alternative pathway. Use of both pathways
      by TLR4 ensures maximal levels of KC and MIP-2 that lead to robust neutrophil
      recruitment. However the MIP-2 generated exclusively by the TRIF pathway is still
      sufficient to cause an influx of neutrophils. In summary we show that TLR
      signaling by tissue macrophages directly controls the synthesis of neutrophil
      attracting chemokines that are essential for the earliest recruitment step in the
      innate immune response to microbial challenge.

PMID- 18322245
TI  - C-reactive protein-bound enzymatically modified low-density lipoprotein does not
      transform macrophages into foam cells.
AB  - The formation of low-density lipoprotein (LDL) cholesterol-loaded macrophage foam
      cells contributes to the development of atherosclerosis. C-reactive protein (CRP)
      binds to atherogenic forms of LDL, but the role of CRP in foam cell formation is
      unclear. In this study, we first explored the binding site on CRP for
      enzymatically modified LDL (E-LDL), a model of atherogenic LDL to which CRP
      binds. As reported previously, phosphocholine (PCh) inhibited CRP-E-LDL
      interaction, indicating the involvement of the PCh-binding site of CRP in binding
      to E-LDL. However, the amino acids Phe66 and Glu81 in CRP that participate in CRP
      PCh interaction were not required for CRP-E-LDL interaction. Surprisingly,
      blocking of the PCh-binding site with phosphoethanolamine (PEt) dramatically
      increased the binding of CRP to E-LDL. The PEt-mediated enhancement in the
      binding of CRP to E-LDL was selective for E-LDL because PEt inhibited the binding
      of CRP to another PCh-binding site-ligand pneumococcal C-polysaccharide. Next, we
      investigated foam cell formation by CRP-bound E-LDL. We found that, unlike free E
      LDL, CRP-bound E-LDL was inactive because it did not transform macrophages into
      foam cells. The function of CRP in eliminating the activity of E-LDL to form foam
      cells was not impaired by the presence of PEt. Combined data lead us to two
      conclusions. First, PEt is a useful compound because it potentiates the binding
      of CRP to E-LDL and, therefore, increases the efficiency of CRP to prevent
      transformation of macrophages into E-LDL-loaded foam cells. Second, the function
      of CRP to prevent formation of foam cells may influence the process of
      atherogenesis.

PMID- 18322246
TI  - The role of sphingosine kinase in a murine model of allergic asthma.
AB  - Asthma is an allergic disease characterized by chronic airway eosinophilia and
      pulmonary infiltration of lymphocytes, particularly of the Th2 subtype,
      macrophages and mast cells. Previous studies have shown a pivotal role for
      sphingosine kinase (SphK) on various proinflammatory cells, such as lymphocyte
      and eosinophil migration and mast cell degranulation. We therefore examined the
      roles of SphK in a murine model of allergic asthma. In mice previously sensitized
      to OVA, i.p. administration of N,N-dimethylsphingosine (DMS), a potent SphK
      inhibitor, significantly reduced the total inflammatory cell infiltrate and
      eosinophilia and the IL-4, IL-5, and eotaxin levels in bronchoalveolar lavage
      fluid in response to inhaled OVA challenge. In addition, DMS significantly
      suppressed OVA-induced inflammatory infiltrates and mucus production in the
      lungs, and airway hyperresponsiveness to methacholine in a dose-dependent manner.
      OVA-induced lymphocyte proliferation and IL-4 and IL-5 secretion were reduced in
      thoracic lymph node cultures from DMS-treated mice. Moreover, similar reduction
      in inflammatory infiltrates, bronchoalveolar lavage, IL-4, IL-5, eotaxin, and
      serum OVA-specific IgE levels was observed in mice with SphK1 knock-down via
      small interfering RNA approach. Together, these data demonstrate the therapeutic
      potential of SphK modulation in allergic airways disease.

PMID- 18322247
TI  - Analysis of HLA-G in maternal plasma, follicular fluid, and preimplantation
      embryos reveal an asymmetric pattern of expression.
AB  - Soluble HLA-G (sHLA-G) secretion by human preimplantation embryos in culture has
      been associated with successful embryo development, and therefore has potential
      to serve as a noninvasive marker of embryo viability. We have examined the
      spatial and temporal expression of HLA-G in embryos of varying developmental
      competence and the role of maternal factors in human embryonic HLA-G expression.
      Embryos that reached blastocyst stage on day 5 showed a higher frequency of sHLA
      G secretion than those at morula or arrested stages (p < 0.05). There was no
      significant difference in sHLA-G secretion between normal embryos and those
      diagnosed as chromosomally abnormal by preimplantation genetic diagnosis. HLA-G
      detected in maternal plasma and follicular fluid did not appear to correlate with
      HLA-G expressed in the embryo or embryo supernatants. Confocal microscopy
      analysis indicated that HLA-G protein expression in embryos was not homogeneous;
      mostly, it was confined to blastocysts localized on trophectoderm and
      trophectoderm projections. Single-particle fluorescent imaging analysis of HLA-G
      on the cell surface of JEG-3 cells showed that HLA-G particles were mostly
      monomeric, but dimeric and higher order oligomers were also observed. These
      results suggest that HLA-G play an important role in preimplantation embryo
      development. However, the observed expression of HLA-G in arrested and
      chromosomally abnormal embryos indicates that HLA-G testing should be used with
      caution and in conjunction with conventional methods of embryo screening and
      selection.

PMID- 18322248
TI  - Tumor cell killing mechanisms of epidermal growth factor receptor (EGFR)
      antibodies are not affected by lung cancer-associated EGFR kinase mutations.
AB  - The epidermal growth factor receptor (EGFR) serves as a molecular target for
      novel cancer therapeutics such as tyrosine kinase inhibitors (TKI) and EGFR Abs.
      Recently, specific mutations in the EGFR kinase domain of lung cancers were
      identified, which altered the signaling capacity of the receptor and which
      correlated with clinical response or resistance to TKI therapy. In the present
      study, we investigated the impact of such EGFR mutations on antitumor cell
      activity of EGFR Abs. Thus, an EGFR-responsive cell line model was established,
      in which cells with tumor-derived EGFR mutations (L858R, G719S, delE746-A750)
      were significantly more sensitive to TKI than wild-type EGFR-expressing cells. A
      clinically relevant secondary mutation (T790M) abolished TKI sensitivity.
      Significantly, antitumor effects of EGFR Abs, including signaling and growth
      inhibition and Ab-dependent cellular cytotoxicity, were not affected by any of
      these mutations. Somatic tumor-associated EGFR kinase mutations, which modulate
      growth inhibition by TKI, therefore do not impact the activity of therapeutic Abs
      in vitro.

PMID- 18322249
TI  - The effect of platelet activation on the hypercoagulability induced by murine
      monoclonal antiphospholipid antibodies.
AB  - BACKGROUND: To identify the mechanisms of the hypercoagulability associated with
      antiphospholipid antibodies, we investigated antibody-mediated platelet
      activation and interference of antibodies with phospholipid-dependent reactions.
      DESIGN AND METHODS: We used two murine monoclonal antibodies, one against beta(2)
      glycoprotein I (7F6G), the other against prothrombin (28F4). Platelet activation
      was assessed by phospholipid-related platelet procoagulant activity. Endogenous
      thrombin potential without activated protein C (ETP(0)) and the activated protein
      C concentration that reduced the ETP(0) by 50% (IC(50)-APC) were determined by
      calibrated automated thrombography. RESULTS: Both monoclonal antibodies mimicked
      the effect of IgG in 11 out of a series of 40 patients with antiphospholipid
      antibodies in thrombography. In the presence of their target, 7F6G and 28F4 at
      200 microg/mL exhibited comparatively low and high binding to platelets and
      elicited low and high levels of procoagulant phospholipids on platelet surface,
      respectively. In platelet-poor plasma, these antibodies induced a 1.6 and >12
      fold increase in IC(50)-APC, respectively, thus providing evidence for a
      procoagulant effect independent of platelet activation. The 84% decrease in
      ETP(0) indicated that 28F4 also displayed an anticoagulant effect. In platelet
      rich plasma, this anticoagulant effect was significantly less (23% decrease in
      ETP(0)), demonstrating that a high increase in procoagulant surfaces by platelet
      activation significantly antagonizes the anticoagulant effect of antiphospholipid
      antibodies. In both types of plasma, the inhibition of thrombin generation
      (reduced ETP(0)) was less than the inhibition of activated protein C activity
      (increased IC(50)-APC). CONCLUSIONS: Our findings show that platelet activation
      reinforces the hypercoagulability induced by competition between antiphospholipid
      antibodies/target complexes and pro- and anticoagulant complexes for phospholipid
      surfaces.

PMID- 18322250
TI  - Improvements in survival of adults diagnosed with acute myeloblastic leukemia in
      the early 21st century.
AB  - Treatment of adults with acute myeloblastic leukemia has changed substantially
      over the past two decades. Currently available estimates of survival do not
      reflect results from present state-of-the-art treatment due to a lag between the
      availability of new treatments and data concerning their effect on survival on
      the population level when traditional cohort analysis is used. We estimated
      trends in age-specific 5- and 10-year relative survival of acute myeloblastic
      leukemia patients aged over 15 years old for 5-year calendar periods from 1980
      1984 through 2000-2004 using data from the Surveillance, Epidemiology, and End
      Results Program. Period analysis was employed to reveal recent developments in
      prognosis. Five and 10-year relative survival improved greatly between 1980-1984
      and 2000-2004 for all patients except those aged over 75 years old. Improvements
      were greatest for patients aged 15-34, with increases in 5- and 10-year relative
      survival of greater than 30% points in this group. Five and 10-year relative
      survival reached 52.3% and 47.9%, respectively, in this group in 2000-2004. Less
      pronounced but still substantial improvements in relative survival were seen in
      the 35-54 and 55-64 age groups. Survival was unchanged, at less than 5%, for
      patients aged over 75 years old. Our period analysis reveals major improvement on
      the population level in long-term prognosis of younger patients with acute
      myeloblastic leukemia, most likely explained by multiple incremental improvements
      in care including better and more specific diagnosis, improvements in and
      extension of the use of stem cell transplantation and high dose therapy, and
      improved supportive care.

PMID- 18322251
TI  - Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry.
AB  - BACKGROUND: Fanconi anemia is an inherited genomic instability syndrome
      associated with progressive bone marrow failure leading to death or the
      requirement for hematopoietic stem cell transplantation, acute myeloid leukemia,
      and solid tumors. Prior epidemiological studies have quantified the risks of bone
      marrow failure, acute myeloid leukemia and solid tumors, but these estimates have
      not been replicated. DESIGN AND METHODS: We assembled a cohort of 181 patients
      with Fanconi anemia mostly from Germany. We calculated the ratio of observed to
      expected cancers, and the risks of bone marrow failure, acute myeloid leukemia,
      and solid tumors by age. RESULTS: The first adverse event was bone marrow failure
      in 66 patients, acute meyloid leukemia in 14 patients and solid tumors in 10
      patients. The ratio of observed to expected cancers was 44 for all cancers, 26
      for all solid tumors, and 868 for acute myeloid leukemia; these increased risks
      were statistically significant. Significantly elevated ratios of observed to
      expected cancers were observed for esophageal (6281), vulvar (2411), head and
      neck (240), breast (34) and brain (23) tumors. Absent or abnormal radii, and a
      five-item congenital abnormality score, were significant risk factors for bone
      marrow failure. The cumulative incidence of bone marrow failure by the age of 10
      years varied from 12.6% in the lowest bone marrow failure risk group to 84% in
      the highest. The relative hazard of bone marrow failure was significantly higher
      in complementation group G versus A (relative hazard=2.2) and in C versus A
      (relative hazard=5.4). CONCLUSIONS: Findings from the German Fanconi Anemia
      Registry cohort validate prior risk estimates, and strongly support the concept
      that Fanconi anemia is a highly penetrant cancer susceptibility syndrome with
      early onset of acute myeloid leukemia and slightly later onset of specific solid
      tumors.

PMID- 18322252
TI  - Bortezomib plus melphalan and prednisone in elderly untreated patients with
      multiple myeloma: updated time-to-events results and prognostic factors for time
      to progression.
AB  - BACKGROUND: New treatment options offering enhanced activity in elderly, newly
      diagnosed patients with multiple myeloma are required. One strategy is to combine
      melphalan and prednisone with novel agents. We previously reported an 89%
      response rate, including 32% complete responses and 11% near complete responses,
      in our phase 1/2 study of bortezomib plus melphalan and prednisone (VMP) in 60
      newly diagnosed multiple myeloma patients with a median age of 75 years. Here, we
      report updated time-to-events data and the impact of poor prognosis factors on
      outcome. DESIGN AND METHODS: Updated analyses of time to biochemical progression
      and overall survival with VMP were conducted, and compared with those of
      historical controls treated with melphalan and prednisone. A univariate analysis
      was performed to evaluate the influence of known prognostic factors on the time
      to progression. RESULTS: After a median follow-up of 26 months, the median time
      to progression with VMP was 27.2 months, compared with 20.0 months with melphalan
      plus prednisone. The median overall survival with VMP was not reached versus 26
      months with melphalan and prednisone; the survival rate at 38 months was 85%
      versus 38%, respectively. Time to progression was not significantly affected by
      elevated beta(2)-microglobulin or lactate dehydrogenase levels, advanced age, or
      cytogenetic abnormalities, but was shorter in patients with albumin < 3 g/dL,
      Karnofsky performance status < or =70%, bone marrow plasma cell infiltration > or
      =40%, and, particularly, high plasma cell proliferative activity (> or = 2.5% S
      phase cells). CONCLUSIONS: VMP is highly active and well tolerated in elderly
      patients with newly diagnosed multiple myeloma, with 85% of patients alive at 3
      years. Moreover, VMP may overcome the poor prognostic impact of various factors,
      particularly cytogenetic abnormalities.

PMID- 18322253
TI  - Bone marrow stromal cells and the upregulation of interleukin-8 production in
      human T-cell acute lymphoblastic leukemia through the CXCL12/CXCR4 axis and the
      NF-kappaB and JNK/AP-1 pathways.
AB  - BACKGROUND: Cytokines released in the bone marrow and thymic microenvironments
      play a key role in the growth of T-cell acute lymphoblastic leukemia. Among such
      cytokines, interleukin-8 is highly expressed in T-cell acute lymphoblastic
      leukemia cells refractory to chemotherapy. In this study we explored whether bone
      marrow stromal cells can regulate IL-8 expression in T-cell acute lymphoblastic
      leukemia and investigated the role of the stromal CXCL12 chemokine in this event.
      We also investigated the roles of the nuclear factor-kappaB and Jun-N-terminal
      kinase (JNK)/activating protein (AP)-1 signaling pathways, which contribute to
      regulate interleukin-8 production in some cells. DESIGN AND METHODS: We analyzed
      the expression of interleukin-8 in primary cells from ten adult patients with T
      cell acute lymphoblastic leukemia when these cells were cultured with bone marrow
      stromal cells or stimulated with exogenous CXCL12. Interleukin-8 mRNA was
      analyzed by a colorimetric assay. Cytokine production was assayed by cytometric
      antibody array and flow cytometry. Nuclear factor-kappaB and JNK/AP-1 activation
      was investigated by using specific inhibitors of these pathways, immunoblotting,
      electrophoretic mobility-shift assay and cell transfection assays. RESULTS: Bone
      marrow stromal cells upregulated interleukin-8 mRNA in T-cell acute lymphoblastic
      leukemia cells through the activity of CXCR4, the CXCL12 receptor, as assessed by
      the use of neutralizing antibodies. Exogenous CXCL12 induced a significant
      increase in the production of IL-8 mRNA and protein in all T-cell acute
      lymphoblastic leukemia cases. We showed that CXCL12 activates the nuclear factor
      kappaB and JNK/AP-1 pathways, and that these events are required for increased
      expression of interleukin-8. Furthermore, the nuclear factor-kappaB and AP-1
      elements of the interleukin-8 promoter are necessary for both constitutive and
      CXCL12-induced interleukin-8 expression. CONCLUSIONS: Interleukin-8 is
      physiologically regulated by the CXCL12/CXCR4 axis and the nuclear factor-kappaB
      and JNK/AP-1 pathways are required for interleukin-8 expression in T-cell acute
      lymphoblastic leukemia. We propose that, by upregulating interleukin-8, the bone
      marrow microenvironment and the CXCL12/CXCR4 axis may play a role in the
      pathogenesis of T-cell acute lymphoblastic leukemia.

PMID- 18322254
TI  - Functional characterization of twelve natural PROS1 mutations associated with
      anticoagulant protein S deficiency.
AB  - BACKGROUND: The molecular mechanisms by which PROS1 mutations result in protein S
      deficiency are still unknown for many of the mutations, particularly for those
      that result in a premature termination codon. The aim of this study was to
      analyze the functional relevance on mRNA and protein expression of 12 natural
      PROS1 mutations associated with protein S deficiency. DESIGN AND METHODS: Five
      mutations were nonsense, three were small frameshift deletions, one was
      c.258,259AG>GT at the 3' end of exon 3, one was p.M640T and the last two were c.
      7C>G and p.L15H, found in double heterozygosis as [c.-7C>G;44T>A]. The apparently
      neutral variant p.R233K was also analyzed. PROS1 cDNA was assessed by reverse
      transcriptase polymerase chain reaction of platelet mRNA. Expression of mutant
      proteins was determined by site-directed mutagenesis and analyses of transiently
      transfected PROS1 mutants in COS-7 cells. RESULTS: Only cDNA from the normal
      allele was observed from the five nonsense mutations, the frameshift deletion
      c.1731delT and from c.258,259AG>GT. Both the normal and the mutated alleles were
      observed from [c.-7C>G;44T>A], c.187,188delTG and p.M640T. Transient expression
      analyses of PROS1 mutants whose mRNA was normally expressed revealed greatly
      reduced secretion of p.L15H and c.1272delA, mild secretion values of p.M640T and
      normal secretion levels of c.-7C>G and, as expected, p.R233K. CONCLUSIONS:
      Whereas the main cause of quantitative protein S deficiency associated with
      missense mutations is defective synthesis, stability or secretion of the mutated
      protein, the main mechanism for the deficiency associated with mutations that
      generate a premature termination codon is not the synthesis of a truncated
      protein, but the exclusion of the mutated allele, probably by nonsense-mediated
      mRNA decay.

PMID- 18322255
TI  - Modulation of erythroid adhesion receptor expression by hydroxyurea in children
      with sickle cell disease.
AB  - BACKGROUND: We investigated adhesion receptor levels on red blood cells,
      reticulocytes and erythroid progenitors from children with sickle cell disease
      treated or not with hydroxyurea. DESIGN AND METHODS: Four groups of patients were
      investigated: (i) children receiving hydroxyurea for severe vaso-occlusive events
      (n=26); (ii) untreated children with a history of vaso-occlusive events (n=20);
      (iii) children with no history of vaso-occlusive events (n=28); and (iv) healthy
      African controls (n=27). Expression of adhesion receptors was analyzed by flow
      cytometry with specific mono-clonal antibodies. RESULTS: Reticulocytes and/or red
      blood cells from the children with sickle cell disease showed significantly
      higher expression of CD36, alpha 4beta 1, Lu/BCAM than those from controls,
      whatever the severity of the disease, as well as less marked increases in
      expression of ICAM-4, CD47 and CD147. Under hydroxyurea treatment, the expression
      of CD36, alpha 4beta 1 and ICAM-4 (to a lesser extent) was decreased, but
      surprisingly the expression of Lu/BCAM (and also CD47 and CD147 to a lesser
      extent) was significantly increased. Alterations of levels of adhesion receptors
      could be recapitulated in two-phase liquid cultures of erythroid progenitors from
      controls and untreated children with a history of vaso-occlusive disease, grown
      in the absence or presence of hydroxyurea. CONCLUSIONS: Our results suggest that
      hydroxyurea acts during erythroid development and modulates adhesion receptor
      expression and function differently, possibly by acting on gene expression and
      the signaling cascade leading to receptor activation.

PMID- 18322256
TI  - Epidemiology of aplastic anemia: a prospective multicenter study.
AB  - BACKGROUND: Aplastic anemia is a rare and severe disease. Its incidence varies
      considerably worldwide. We aimed at describing the epidemiology of this disease,
      including the incidence, mortality and survival trends, in a well-defined
      population. DESIGN AND METHODS: Since 1980, a case-control surveillance study of
      aplastic anemia has been carried out by a cooperative group, in the metropolitan
      area of Barcelona. Inclusion is dependent on the patient having at least two of
      the following features: white blood cell count < or = 3.5 x 10(9)/L, platelet
      count < or = 50 x 10(9)/L, hemoglobin <10 g/L or hematocrit of <30%; when only
      one of these last two criteria is fulfilled, a reticulocyte count of < or = 30 x
      10(9)/L is also required. The bone marrow biopsy has to be compatible with the
      diagnosis of aplastic anemia. RESULTS: Between 1980 and 2003, a total of 235
      cases of aplastic anemia were identified. The overall incidence was 2.34 per
      million inhabitants per year and the incidence increased with age. Most of the
      cases were classified as severe or very severe aplastic anemia. Survival rates at
      3 months, and at 2 and 15 years after the diagnosis were 73%, 57%, and 51%,
      respectively. Advanced age and more severe disease at the time of diagnosis were
      associated with a lower survival rate. There was a trend to a better 2-year
      survival rate among patients treated with bone marrow transplantation. Forty-nine
      cases (20.8%) were exposed to drugs reported to be associated with aplastic
      anemia, and 21 (8.9%) to toxic agents. CONCLUSIONS: The incidence of aplastic
      anemia in Barcelona is low but the case fatality rate is high. Advanced age and
      severe disease at the time of diagnosis were associated with decreased survival.

PMID- 18322257
TI  - In vitro validation of gamma-secretase inhibitors alone or in combination with
      other anti-cancer drugs for the treatment of T-cell acute lymphoblastic leukemia.
AB  - BACKGROUND: Activating NOTCH1 mutations are common in T-cell acute lymphoblastic
      leukemia. Inhibition of NOTCH1 signaling with gamma-secretase inhibitors causes
      cell cycle block, but only after treatment for several days. We further
      documented the effects of gamma-secretase inhibitor treatment on T-cell acute
      lymphoblastic leukemia cell lines and tested whether combining gamma-secretase
      inhibitors with other anti-cancer drugs offers a therapeutic advantage. DESIGN
      AND METHODS: The effect of gamma-secretase inhibitor treatment and combinations
      of gamma-secretase inhibitors with chemotherapy or glucocorticoids was assessed
      on T-cell acute lymphoblastic leukemia cell lines. We sequenced NOTCH1 in T-cell
      acute lymphoblastic leukemia cases with ABL1 fusions and tested combinations of
      gamma-secretase inhibitors and the ABL1 inhibitor imatinib in a T-cell acute
      lymphoblastic leukemia cell line. RESULTS: gamma-secretase inhibitor treatment
      for 5-7 days reversibly inhibited cell proliferation, caused cell cycle block in
      sensitive T-cell acute lymphoblastic leukemia cell lines, and caused
      differentiation of some T-cell acute lymphoblastic leukemia cell lines. Treatment
      for 14 days or longer was required to induce significant apoptosis. The cytotoxic
      effects of the chemotherapeutic agent vincristine were not significantly enhanced
      by addition of gamma-secretase inhibitors to T-cell acute lymphoblastic leukemia
      cell lines, but gamma-secretase inhibitor treatment sensitized cells to the
      effect of dexamethasone. NOTCH1 mutations were identified in all T-cell acute
      lymphoblastic leukemia patients with ABL1 fusions and in a T-cell acute
      lymphoblastic leukemia cell line expressing NUP214-ABL1. In this cell line, the
      anti-proliferative effect of imatinib was increased by pre-treatment with gamma
      secretase inhibitors. CONCLUSIONS: Short-term treatment of T-cell acute
      lymphoblastic leukemia cell lines with gamma-secretase inhibitors had limited
      effects on cell proliferation and survival. Combinations of gamma-secretase
      inhibitors with other drugs may be required to obtain efficient therapeutic
      effects in T-cell acute lymphoblastic leukemia, and not all combinations may be
      useful.

PMID- 18322258
TI  - A prospective analysis of the genotypic diversity and dynamics of the Candida
      albicans colonizing flora in neutropenic patients with de novo acute leukemia.
AB  - BACKGROUND: Genotyping studies have shown heterogeneity of Candida albicans flora
      in patients with human immunodeficiency virus infection, with possible co
      existence of multiple clones with distinct resistance patterns. We report the
      result of a prospective study aimed at investigating the dynamics and
      heterogeneity of C. albicans flora in patients with de novo acute leukemia.
      DESIGN AND METHODS: Between 2001 and 2003, 66 consecutive adults with newly
      diagnosed acute leukemia were monitored for Candida colonization. From 19
      patients with repeated multi-site C. albicans colonization, eight were randomly
      selected and multiple isolates from each individual mucosal site were genotyped
      sequentially over time using microsatellite markers. RESULTS: Despite topical use
      of polyenes, 60.6% of the patients were colonized repeatedly and at multiple
      sites. Altogether, 2,730 peripheral samples were cultured, 379 (13.9%) of which
      yielded yeasts. C. albicans was the most common species recovered (68%). From
      eight randomly selected patients colonized with C. albicans, 429 isolates were
      genotyped. Seven patients carried a unique genotype which was identical in all
      body niches and over the period of study. In one case, minor genotypic
      differences were observed. None of the patients shared C. albicans clones with
      identical genotypic profiles. Candidemia occurred in one of eight patients and
      the blood strain genotype did not differ from those of colonizing isolates. The
      genotypic profile was not altered by topical and/or systemic use of antifungal
      agents in any of the patients. CONCLUSIONS: In patients with de novo acute
      leukemia, genetic evolution of the colonizing C. albicans flora and selection of
      variants or replacement of the original strain upon antifungal drug pressure or
      nosocomial transmission are rare events.

PMID- 18322259
TI  - Quality of life of female caregivers of children with sickle cell disease: a
      survey.
AB  - Caring for a child with sickle cell disease poses extra demands on parents, both
      practically and psychologically, which may influence their quality of life. Since
      families of children with sickle cell disease in the Netherlands usually belong
      to immigrant communities with a low socio-economic status, there may be an
      additional strain on caregivers. The aim of the present study was to evaluate the
      quality of life of caregivers of children with sickle cell disease. The quality
      of life of female caregivers of sickle cell disease patients, measured with the
      TNO-AZL Adult Quality of Life questionnaire, was compared to the norm data of
      healthy Dutch females (n=700) and female caregivers of healthy children with the
      same socio-economic status and ethnic background (socio-economic status control
      group). Groups were compared by the Mann-Whitney U test. Point estimates and 95%
      confidence intervals of the median difference are presented. The results of
      questionnaires of 54 caregivers of children with sickle cell disease and 28
      caregivers of a control group of the same socio-economic status were analyzed.
      Caregivers of patients with sickle cell disease had a significantly lower quality
      of life on all subscales compared to the Dutch norm population. Compared to the
      control group of the same socio-economic status, the quality of life of
      caregivers of patients with sickle cell disease was significantly lower on the
      subscales depressive moods, daily activities and vitality. In this first study
      reporting on the quality of life of caregivers of children with sickle cell
      disease, we demonstrate a reduced quality of life in these caregivers compared to
      the healthy Dutch female population and caregivers of healthy children with the
      same socio-economic status.

PMID- 18322260
TI  - Update to the AHA/ASA recommendations for the prevention of stroke in patients
      with stroke and transient ischemic attack.

PMID- 18322261
TI  - More evidence supporting a "brain code" protocol for reversal of transtentorial
      herniation.

PMID- 18322262
TI  - Alpha-synuclein, pesticides, and Parkinson disease: a case-control study.
AB  - BACKGROUND: Aggregation and fibrillization of the alpha-synuclein protein
      (encoded by the SNCA gene) may represent key events in the pathogenesis of
      Parkinson disease (PD). Variability in the length of a dinucleotide repeat
      sequence (REP1) within the SNCA promoter confers susceptibility to sporadic PD.
      Pesticide exposures may also confer susceptibility to PD. Our objective was to
      test possible joint effects of SNCA REP1 genotypes and pesticide exposures on the
      risk of PD. METHODS: This was a case-control study. Cases were recruited
      prospectively from the Department of Neurology of the Mayo Clinic, Rochester, MN,
      after June 1, 1996. The control subjects included unaffected siblings of cases
      and unrelated population control subjects. We assessed pesticide exposures by
      telephone interview and genotyped SNCA REP1. Odds ratios (ORs) and 95% CIs were
      determined using conditional logistic regression models. RESULTS: There were 833
      case-control pairs. We observed an increased risk of PD with increasing SNCA REP1
      bp length (OR, 1.18 for each score unit; 95% CI, 1.02-1.37; p = 0.03). Pesticide
      exposures were associated with PD in younger subjects only (lowest quartile of
      age at study, <or=59.8 years; OR, 1.80; 95% CI, 1.12-2.87; p = 0.01 for all
      pesticides; OR, 2.46; 95% CI, 1.34-4.52; p = 0.004 for herbicides). In
      multivariate analyses, both SNCA REP1 score and pesticide exposures were
      significantly associated with PD in younger subjects, but there were no pairwise
      interactions. CONCLUSIONS: Our findings suggest that SNCA REP1 genotype and
      herbicides have independent effects on risk of Parkinson disease, primarily in
      younger subjects.

PMID- 18322264
TI  - Influence of the stroke code activation source on the outcome of acute ischemic
      stroke patients.
AB  - INTRODUCTION: In our metropolitan area, the Stroke Code (SC) system allows
      immediate transfer of patients with acute stroke to a stroke center. It may be
      activated by community hospitals (A), emergency medical services (EMS, B), or the
      emergency department of the stroke center (C). Our aim was to analyze whether the
      SC activation source influences the access to thrombolytic therapy and outcome of
      patients with ischemic stroke. METHODS: We prospectively registered patients with
      ischemic stroke admitted to the acute stroke unit who arrived through the SC
      system. The primary outcome variable was good outcome at discharge (Rankin Scale
      <or= 2). Secondary outcome was neurologic improvement >or=4 in National
      Institutes of Health Stroke Scale (NIHSS) score or NIHSS score 0 to 1 at 24
      hours. RESULTS: A total of 262 consecutive patients with hyperacute ischemic
      stroke were studied; the SC source was A in 112, B in 57, and C in 92. Median
      time from onset to admission was longer in Group A and stroke severity higher in
      Groups B and C. Percentage of tPA administration was higher in patients from
      Groups B and C (27%, 54%, and 46% of patients; p = 0.001). With respect to Group
      A, Group B was associated with good outcome with an odds of 2.9 (1.2-6.6; p =
      0.01), and Group C with an odds of 2.4 (1.1-4.9; p = 0.01) after adjustment for
      age and stroke severity at baseline. Patients coming via levels B and C were more
      likely to improve at 24 hours. CONCLUSIONS: Patients arriving directly to the
      stroke center via emergency medical services or on their own receive neurologic
      attention sooner, are more frequently treated with tPA, and have better clinical
      outcome than those patients who are first taken to a community hospital.

PMID- 18322265
TI  - New VAPB deletion variant and exclusion of VAPB mutations in familial ALS.
AB  - OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a progressive,
      neurodegenerative disorder involving upper and lower motor neurons. The vesicle
      associated membrane protein B (VAPB) gene has been genetically linked to ALS in
      several large Brazilian families in which the disorder is caused by a proline to
      serine mutation at codon 56 (P56S). No additional mutations have been identified.
      METHODS: To establish the prevalence of VAPB mutations, we screened 80 familial
      ALS samples by DNA sequencing. RESULTS: Our study failed to identify any novel
      VAPB gene mutations but identified a single Brazilian family harboring the P56S
      mutation. In a second familial ALS case, we identified a three-base pair deletion
      within exon 5 of the VAPB gene that deleted the serine residue at position 160
      (Delta S160). This variant is detected in a normal population at low frequency
      (0.45%). Analyses of homology alignment and secondary structure predict that this
      deletion significantly alters the structure of VAPB, although a GFP-Delta S160
      VAPB fusion protein demonstrates a wild-type subcellular localization. This
      contrasts the aberrant localization observed in a GFP-P56S VAPB fusion protein.
      The allele frequency of Delta S160 in patients with sporadic ALS does not differ
      significantly from that in the normal population. CONCLUSIONS: Mutations in the
      VAPB gene are rare and the Delta S160 variant does not contribute to the
      development of amyotrophic lateral sclerosis.

PMID- 18322266
TI  - Seeking what's best during the transition to adult day health services.
AB  - Family caregivers provide more than 80% of the long-term care for elders in the
      United States and experience a variety of transitions that are intertwined with
      those of their elders. Previous research on health care transitions documents
      problems elders and family caregivers encountered following hospitalization,
      following nursing home admission, and in adjusting to home health care. Little is
      known about the transition to adult day health services (ADHS). The purpose of
      this study was (a) to examine family caregivers' perspectives on the transition
      to ADHS and (b) to develop a situation-specific theory to guide interventions for
      elders and their family caregivers during the transition. Semistructured
      interviews were conducted with 16 family caregivers 1 month and 3 months
      following the elder's enrollment in ADHS. The constant comparative method was
      used in analyzing the data. The findings indicate that family caregivers
      consistently sought what was best for elders throughout the transition.

PMID- 18322263
TI  - Safety and efficacy of galantamine in subjects with mild cognitive impairment.
AB  - OBJECTIVE: To assess the safety of galantamine in subjects with mild cognitive
      impairment (MCI), the ability of galantamine to benefit cognition and global
      functioning in subjects with MCI, and the ability of galantamine to delay
      conversion to dementia. METHODS: In two studies, 2,048 subjects, 990 in Study 1
      and 1,058 in Study 2, with a Clinical Dementia Rating (CDR) = 0.5, CDR memory
      score > or =0.5, without dementia were randomized to double-blind galantamine (16
      24 mg/day) or placebo for 24 months. Primary efficacy endpoint at month 24 was
      number (%) of subjects who converted from MCI to dementia (CDR > or = 1.0).
      RESULTS: There were no differences between galantamine and placebo in 24-month
      conversion rates (Study 1: 22.9% [galantamine] vs 22.6% [placebo], p = 0.146;
      Study 2: 25.4% [galantamine] vs 31.2% [placebo], p = 0.619). Mean CDR-sum of
      boxes declined less with galantamine than placebo at 12 and 24 months in Study 1
      (p = 0.024 [12 months] and p = 0.028 [24 months]), but not in Study 2 (p = 0.662
      [12 months] and p = 0.056 [24 months]). Digit Symbol Substitution Test scores
      improved with galantamine in Study 1 at 12 months and in Study 2 at 24 months
      (Study 1: p = 0.009 [month 12] and p = 0.079 [Month 24]; Study 2: p = 0.154
      [month 12] and p = 0.020 [month 24]). The most frequently reported adverse event
      was nausea (galantamine, 29%; placebo, 10%). Serious AEs occurred in 19% of each
      group. Mortality of the cohort after retrospectively determining the status of
      subjects (98.3%) at 24 months was 1.4% (galantamine) and 0.3% (placebo); RR (95%
      CI), 1.70 (1.00, 2.90). CONCLUSIONS: Galantamine failed to significantly
      influence conversion to dementia. Galantamine was generally well tolerated.
      Whereas recorded mortality was greater in the galantamine group than in the
      placebo group in the original per-protocol assessment, a post hoc analysis of the
      cohort was consistent with no increased risk.

PMID- 18322267
TI  - The leopard cannot change his spots, or can he? Culture and the development of
      lay theories of change.
AB  - Chinese and Canadian children were compared to examine cultural and developmental
      differences in lay theories of change: implicit beliefs about how the world
      develops and changes over time. Chinese and Canadian children (ages 7, 9, and 11
      years) made predictions about future performance, relationships, happiness, and
      parental incomes based on a series of scenarios. Overall, the Chinese children
      predicted greater change than did the Canadian children, indicating that they
      believed more in change than did the Canadians. Moreover, cultural differences
      increased significantly with age: In comparison with their Canadian counterparts,
      Chinese children made no more change predictions at age 7, made slightly more
      change predictions at age 9, and made significantly more change predictions at
      age 11. This was true for questions starting with an extremely positive or
      negative state and those starting with a neutral state. Reasons for cultural and
      developmental differences were discussed.

PMID- 18322268
TI  - Identification of an alternatively spliced isoform of carbonic anhydrase XII in
      diffusely infiltrating astrocytic gliomas.
AB  - Carbonic anhydrase XII (CA XII) is a transmembrane enzyme that is associated with
      neoplastic growth. CA XII has been proposed to be involved in acidification of
      the extracellular milieu, creating an appropriate microenvironment for rapid
      tumor growth. Because RNA sequence databases have indicated that two isoforms of
      CA XII might exist in human tissues, and because alternatively spliced protein
      forms have been linked to aggressive behavior of cancer cells, we designed a
      study to evaluate the presence of the two forms of CA XII in diffuse
      astrocytomas, a tumor type known for its aggressive and often noncurable
      behavior. Reverse transcription PCR of tumor samples surprisingly revealed that
      CA XII present in diffuse astrocytomas is mainly encoded by a shorter mRNA
      variant. We further showed by Western blotting that anti-CA XII antibody
      recognized both isoforms in the glioblastoma cell lines, and we then evaluated
      the expression of CA XII in astrocytomas using immunohistochemistry and
      correlated the results with various clinicopathological and molecular factors. Of
      370 diffusely infiltrating astrocytomas, 363 cases (98%) showed immunoreactions
      for CA XII. Importantly, CA XII expression correlated with poorer patient
      prognosis in univariate (p = 0.010, log-rank test) and multivariate survival
      analyses (p = 0.039, Cox analysis). From these results, we conclude that CA XII
      is commonly expressed in diffuse astrocytomas and that it might be used as a
      biomarker of poor prognosis. The absence of 11 amino acids in the shorter
      isoform, which seems to be common in astrocytomas, may affect the normal
      quaternary structure and biological function of CA XII.

PMID- 18322269
TI  - Cadherin switching.
AB  - The cadherin molecules at adherens junctions have multiple isoforms. Cadherin
      isoform switching (cadherin switching) occurs during normal developmental
      processes to allow cell types to segregate from one another. Tumor cells often
      recapitulate this activity and the result is an aggressive tumor cell that gains
      the ability to leave the site of the tumor and metastasize. At present, we
      understand some of the mechanisms that promote cadherin switching and some of the
      pathways downstream of this process that influence cell behavior. Specific
      cadherin family members influence growth-factor-receptor signaling and Rho
      GTPases to promote cell motility and invasion. In addition, p120-catenin probably
      plays multiple roles in cadherin switching, regulating Rho GTPases and
      stabilizing cadherins.

PMID- 18322270
TI  - Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in
      development and disease.
AB  - The secreted Frizzled-related proteins (SFRPs) are a family of soluble proteins
      that are structurally related to Frizzled (Fz) proteins, the serpentine receptors
      that mediate the extensively used cell-cell communication pathway involving Wnt
      signalling. Because of their homology with the Wnt-binding domain on the Fz
      receptors, SFRPs were immediately characterised as antagonists that bind to Wnt
      proteins to prevent signal activation. Since these initial studies, interest in
      the family of SFRPs has grown progressively, offering new perspectives on their
      function and mechanism of action in both development and disease. These studies
      indicate that SFRPs are not merely Wnt-binding proteins, but can also antagonise
      one another's activity, bind to Fz receptors and influence axon guidance,
      interfere with BMP signalling by acting as proteinase inhibitors, and interact
      with other receptors or matrix molecules. Furthermore, their expression is
      altered in different types of cancers, bone pathologies, retinal degeneration and
      hypophosphatemic diseases, indicating that their activity is fundamental for
      tissue homeostasis. Here we review some of the debated aspects of SFRP-Wnt
      interactions and discuss the new and emerging roles of SFRPs.

PMID- 18322271
TI  - Effect of basolateral adenosine triphosphate on chloride secretion by bovine
      oviductal epithelium.
AB  - The composition of the fluid within the oviduct is largely determined by the
      secretory and absorptive activities of the oviduct epithelium. The present study
      explored the effects of basolateral nucleotide stimulation on ion transport in
      the bovine oviduct using the chamber short-circuit current technique. Basolateral
      application of ATP induced a rapid transient increase in ion secretion by oviduct
      epithelial monolayers in a concentration-dependent manner. The ATP-induced short
      circuit current (I(SC)) response was preserved in the presence of amiloride,
      whereas it was reduced in the absence of extracellular chloride or in the
      presence of bumetanide. The channels underlying the chloride secretory response
      were identified as Ca(2+)-activated Cl(-) channels and CFTR. The ATP-induced Cl(
      ) secretory response was largely preserved in the absence of extracellular Ca(2+)
      but was significantly reduced in the presence of BAPTA-am (1,2-bis(2
      aminophenoxy)ethane N,N,N',N'-tetraacetic acid-acetomethoxy ester), thapsigargin,
      or 2-APB (2-aminoethoxydiphenylborate), demonstrating an important role for
      intracellular Ca(2+) signaling in mediating these effects. A nucleotide potency
      profile of ATP = UTP (uridine triphosphate) > ADP, sensitivity to suramin, and
      cross-desensitization by basolateral UTP suggests that ATP exerted its effects on
      chloride secretion through the purinergic receptor P2Y, G protein-coupled 2, and
      the presence of the P2RY2 gene was confirmed by RT-PCR. These results provide
      strong evidence that purinergic signaling constitutes a key mechanism of
      regulating chloride secretion and thus fluid formation in the bovine oviduct.

PMID- 18322272
TI  - Disruption of lipid rafts induces gonadotropin release in ovine pituitary and
      LbetaT2 gonadotroph cells.
AB  - In order to better understand the cellular mechanisms underlying LH and FSH
      secretion, we have addressed the contribution of lipid rafts to the secretion of
      gonadotropins. We used methyl-beta-cyclodextrin (MbetaCD), a cholesterol
      sequestering agent, on an LbetaT2 murine gonadotroph cell line and on primary
      cultures of ovine pituitary cells. We found that in both systems, cholesterol
      depletion by MbetaCD induced a fast and substantial release of LH in the absence
      of natural stimulation by GnRH. In ovine pituitary cells, MbetaCD-mediated LH
      release was shown to be independent of protein synthesis. Twenty-four hours after
      MbetaCD treatment, there was no loss of cell viability and full recovery of LH
      secretory capabilities, as determined by GnRH or MbetaCD treatment. In addition,
      our data suggest the existence of a pool of LH that is not released by GnRH
      treatment but that is released by MbetaCD treatment. Finally, in ovine pituitary
      cells, MbetaCD treatment induced FSH secretion. Importantly, these in vitro data
      are supported by in vivo studies, because MbetaCD injected into the pituitary
      glands of anaesthetized sheep reproducibly induced a peak of LH release.

PMID- 18322273
TI  - Multiple signals regulate phospholipase CBeta3 in human myometrial cells.
AB  - Phospholipase CB3 (PLCB3) serine(1105) (S(1105)), a substrate for multiple
      protein kinases, represents a potential point of convergence of several signaling
      pathways in the myometrium. To explore this hypothesis, the regulation of PLCB3
      S(1105) phosphorylation (P-S(1105)) was studied in immortalized and primary human
      myometrial cells. 8-[4-chlorophenylthio] (CPT)-cAMP and calcitonin gene-related
      peptide (CALCA) transiently increased P-S(1105). Relaxin also stimulated P
      S(1105); this effect was partially blocked by the protein kinase A (PRKA)
      inhibitor, Rp-8-CPT-cAMPS. Oxytocin, which stimulates Galphaq-mediated pathways,
      also rapidly increased P-S(1105), as did prostaglandin F2alpha and ATP. Oxytocin
      stimulated phosphorylation was blocked by protein kinase C (PRKC) inhibitor
      Go6976 and by pretreatment overnight with a phorbol ester. Cypermethrin, a PP2B
      phosphatase inhibitor, but not okadaic acid, a PP1/PP2A inhibitor, prolonged the
      effect of CALCA on P-S(1105), whereas the reverse was the case for the oxytocin
      stimulated increase in P-S(1105). PLCB3 was the predominant PLC isoform expressed
      in the myometrial cells and PLCB3 short hairpin RNA constructs significantly
      attenuated oxytocin-stimulated increases in intracellular calcium. oxytocin
      induced phosphatidylinositol (PI) turnover was inhibited by CPT-cAMP and okadaic
      acid, but was enhanced by pretreatment with Go6976. CPT-cAMP inhibited oxytocin
      stimulated PI turnover in the presence of overexpressed PLCB3, but not
      overexpressed PLCB3-S(1105)A. These data demonstrate that both negative crosstalk
      from the cAMP/PRKA pathway and a negative feedback loop in the oxytocin/G
      protein/PLCB pathway involving PRKC operate in myometrial cells and suggest that
      different protein phosphatases predominate in mediating P-S(1105)
      dephosphorylation in these pathways. The integration of multiple signal
      components at the level of PLCB3 may be important to its function in the
      myometrium.

PMID- 18322274
TI  - Cyclosporin A promotes growth and invasiveness in vitro of human first-trimester
      trophoblast cells via MAPK3/MAPK1-mediated AP1 and Ca2+/calcineurin/NFAT
      signaling pathways.
AB  - Cyclosporin A (CsA) has provided the pharmacologic foundation for organ
      transplantation as a calcineurin inhibitor blocking T-cell activation. We have
      demonstrated that CsA promoted trophoblast viability/proliferation and invasion
      in vitro. In the present study, we further investigated the intracellular
      signalling pathways involved in enhancing cell viability/proliferation and
      invasiveness of the human trophoblast induced by CsA. We showed that blocking
      mitogen-activated protein kinase 3 (MAPK3)/MAPK1 signaling by U0126 attenuated
      CsA-increased cell viability and invasiveness of trophoblasts. Cyclosprin A
      inhibited ionomycin-stimulated nuclear factor of activated T-cells (NFAT)
      transactivation in JAR cells and reversed the ionomycin-inhibited trophoblast
      invasiveness. However, either activating calcineurin by ionomycin, resulting in
      NFAT transactivation, or inhibiting NFAT using an NFAT inhibitor had no effect on
      trophoblast cell viability/proliferation and apoptosis in vitro. Hence, the CsA
      induced promotion of trophoblast growth and invasion occurred by overlapping but
      independent pathways. The MAPK3/MAPK1 pathway was essential for both trophoblast
      growth and invasion, whereas the Ca(2+)/calcineurin/NFAT pathway was only
      involved in the CsA-promoted trophoblast invasiveness. Finally, potential cross
      talk between MAPK3/MAPK1 and Ca(2+)/calcineurin/NFAT and its relationship to
      activator protein 1 activation was investigated. Our findings explored possible
      signal transduction pathways modulated by CsA, which may lead to the expansion of
      the clinical applications of this drug.

PMID- 18322275
TI  - Difference in Ca2+ oscillation-inducing activity and nuclear translocation
      ability of PLCZ1, an egg-activating sperm factor candidate, between mouse, rat,
      human, and medaka fish.
AB  - Mouse phospholipase C, zeta 1 (PLCZ1), a strong candidate of egg-activating sperm
      factor, induces Ca(2+) oscillations and accumulates into formed pronucleus (PN)
      when expressed by cRNA injection. These activities were compared among mouse and
      human PLCZ1, newly cloned rat Plcz1, and medaka fish plcz1. The PLCZ1 proteins of
      the four species have an approximately homologous sequence of nuclear
      localization signal. However, the nuclear translocation ability was defective in
      rat, human, and medaka PLCZ1 expressed in mouse eggs. Rat PLCZ1 could not enter
      rat PN, whereas mouse PLCZ1 could. Mouse and human PLCZ1 translocated into the
      nucleus of COS-7 cells transfected with cDNA. There was little medaka PLCZ1
      accumulated in the nucleus, and rat PLCZ1 was never located in the nucleus. All
      PLCZ1 proteins including fish could induce Ca(2+) oscillations in mouse eggs, but
      the activity was variable in the order of human >> mouse > medaka >> rat,
      estimated from minimal RNA concentration to induce Ca(2+) spikes. Ca(2+)
      oscillations by human PLCZ1 continued far beyond the time of PN formation
      (T(PN)), whereas those by mouse PLCZ1 ceased slightly before T(PN). High
      frequency Ca(2+) spikes by overexpressed rat PLCZ1 stopped far before T(PN),
      possibly by feedback inhibition. Ca(2+) oscillations by fertilization of rat eggs
      stopped at T(PN), despite defective nuclear translocation of rat PLCZ1. Thus,
      PLCZ1 sequestration into PN participates in termination of Ca(2+) oscillations at
      the interphase of mouse embryos but does not always operate in other mammals,
      notably in rat embryos.

PMID- 18322276
TI  - Expression of stimulated by retinoic acid gene 8 (Stra8) in spermatogenic cells
      induced by retinoic acid: an in vivo study in vitamin A-sufficient postnatal
      murine testes.
AB  - Vitamin A is required for male fertility and normal spermatogenesis. Retinoic
      acid (RA), an active metabolite of vitamin A, is necessary for spermatogonial
      maturation and proper entry of germ cells into meiotic prophase in the postnatal
      testes. The expression of Stra8, which is essential for successful meiosis in
      both male and female gonads and normal spermatogenesis, is directly related to
      the availability of RA. This study examined the developmental expression pattern
      of Stra8 transcript in both male and female gonads, provided specific cellular
      localization of STRA8 protein in the postnatal and adult testis, and investigated
      RA actions in adult germ cells in a vitamin A-sufficient condition. The peak of
      Stra8 mRNA expression coincided with the onset of meiosis in postnatal testes.
      STRA8 protein was detected in gonocytes as early as 5 days postpartum. The
      expression of STRA8 protein in the neonatal testes was not uniform among
      spermatogonia, perhaps heralding the asynchronous beginning of spermatogenesis.
      In adult testes, the highest level of Stra8 mRNA and protein was found in
      seminiferous epithelial stages VI-VIII. STRA8 protein was localized to some type
      A and B spermatogonia, preleptotene spermatocytes, and early leptotene
      spermatocytes. In the vitamin A-sufficient adult testes, RA but not retinol
      acetate stimulated Stra8 mRNA expression. STRA8 protein expression in adult
      spermatogonia was induced by RA stimulation, suggesting its role in
      spermatogonial differentiation. Retinoic acid also increased the number of
      preleptotene spermatocytes exhibiting 5-bromo-2-deoxyuridine incorporation,
      indicating a more synchronized premeiotic DNA replication.

PMID- 18322277
TI  - The role of homeobox protein distal-less 3 and its interaction with ETS2 in
      regulating bovine interferon-tau gene expression-synergistic transcriptional
      activation with ETS2.
AB  - Distal-less 3 (DLX3), a homeodomain transcription factor required for placental
      development in the mouse, modestly transactivates hCG-alpha subunit gene (hCGA)
      expression in human choriocarcinoma cells. Because hCG and interferon-tau (IFNT)
      are expressed in trophectoderm of primates and ruminants, respectively, we have
      tested the hypothesis that DLX3 regulates the genes for IFNT (IFNT). A bovine
      IFNT1 promoter (-457 to +66), linked to a luciferase (luc) reporter, was
      transactivated approximately 20-fold by overexpressing DLX3 in human JAr cells.
      Elimination of a potential DLX3-binding site (-54 GATAATGAG -46) by either
      truncation or mutagenesis abolished this effect. A sequence (-59 to -44)
      encompassing this site bound DLX3 specifically. Coexpression of DLX3 and ETS2,
      which is known to be a key regulator of IFNT expression, increased reporter
      activity by more than 250-fold, whereas deletion of the established ETS2 site (
      79 to -70) eliminated the ability of DLX3 to transactivate the gene. Conversely,
      mutation of the DLX3 site significantly reduced the transactivational effects of
      ETS2. Both DLX3 and ETS2 are coexpressed in JAr cells and in an IFNT-producing,
      bovine trophoblast cell line, CT-1. The two can be immunoprecipitated together as
      a complex from CT-1 cells, and RNAi-mediated, partial knockdown of DLX3
      expression reduced the production of IFNT by approximately 50+. Together, these
      results suggest that DLX3 has a central role in controlling IFNT gene expression
      by associating with ETS2 on the IFNT promoter.

PMID- 18322278
TI  - Functional redundancy of TGF-beta family type I receptors and receptor-Smads in
      mediating anti-Mullerian hormone-induced Mullerian duct regression in the mouse.
AB  - Amniotes, regardless of genetic sex, develop two sets of genital ducts: the
      Wolffian and Mullerian ducts. For normal sexual development to occur, one duct
      must differentiate into its corresponding organs, and the other must regress. In
      mammals, the Wolffian duct differentiates into the male reproductive tract,
      mainly the vasa deferentia, epididymides, and seminal vesicles, whereas the
      Mullerian duct develops into the four components of the female reproductive
      tract, the oviducts, uterus, cervix, and upper third of the vagina. In males, the
      fetal Leydig cells produce testosterone, which stimulates the differentiation of
      the Wolffian duct, whereas the Sertoli cells of the fetal testes express anti
      Mullerian hormone, which activates the regression of the Mullerian duct. Anti
      Mullerian hormone is a member of the transforming growth factor-beta (TGF-beta)
      family of secreted signaling molecules and has been shown to signal through the
      BMP pathway. It binds to its type II receptor, anti-Mullerian hormone receptor 2
      (AMHR2), in the Mullerian duct mesenchyme and through an unknown mechanism(s);
      the mesenchyme induces the regression of the Mullerian duct mesoepithelium. Using
      tissue-specific gene inactivation with an Amhr2-Cre allele, we have determined
      that two TGF-beta type I receptors (Acvr1 and Bmpr1a) and all three BMP receptor
      Smads (Smad1, Smad5, and Smad8) function redundantly in transducing the anti
      Mullerian hormone signal required for Mullerian duct regression. Loss of these
      genes in the Mullerian duct mesenchyme results in male infertility due to
      retention of Mullerian duct derivatives in an otherwise virilized male.

PMID- 18322279
TI  - In utero exposure to di-(2-ethylhexyl) phthalate exerts both short-term and long
      lasting suppressive effects on testosterone production in the rat.
AB  - We examined the effects of fetal exposure to a wide range of di-(2-ethylhexyl)
      phthalate (DEHP) doses on fetal, neonatal, and adult testosterone production.
      Pregnant rats were administered DEHP from Gestational Day (GD) 14 to the day of
      parturition (Postnatal Day 0). Exposure to between 234 and 1250 mg/kg/day of DEHP
      resulted in increases in the absolute volumes of Leydig cells per adult testis.
      Despite this, adult serum testosterone levels were reduced significantly compared
      to those of controls at all DEHP doses. Organ cultures of testes from GD20 rats
      exposed in utero to DEHP showed dose-dependent reductions in basal testosterone
      production. Surprisingly, however, no significant effect of DEHP was found on hCG
      induced testosterone production by GD20 testes, suggesting that the inhibition of
      basal steroidogenesis resulted from the alteration of molecular events upstream
      of the steroidogenic enzymes. Reduced fetal and adult testosterone production in
      response to in utero DEHP exposure appeared to be unrelated to changes in
      testosterone metabolism. In view of the DEHP-induced reductions in adult
      testosterone levels, a decrease in the expression of steroidogenesis-related
      genes was anticipated. Surprisingly, however, significant increases were seen in
      the expression of Cyp11a1, Cy17a1, Star, and Tspo transcripts, suggesting that
      decreased testosterone production after birth could not be explained by decreases
      in steroidogenic enzymes as seen at GD20. These changes may reflect an increased
      number of Leydig cells in adult testes exposed in utero to DEHP rather than
      increased gene expression in individual Leydig cells, but this remains uncertain.
      Taken together, these results demonstrate that in utero DEHP exposure exerts both
      short-term and long-lasting effects on testicular steroidogenesis that might
      involve distinct molecular targets in fetal and adult Leydig cells.

PMID- 18322280
TI  - Semper fidelis--consumer protection for patients with implanted medical devices.

PMID- 18322281
TI  - Genetic determinants of response to warfarin during initial anticoagulation.
AB  - BACKGROUND: Genetic variants of the enzyme that metabolizes warfarin, cytochrome
      P-450 2C9 (CYP2C9), and of a key pharmacologic target of warfarin, vitamin K
      epoxide reductase (VKORC1), contribute to differences in patients' responses to
      various warfarin doses, but the role of these variants during initial
      anticoagulation is not clear. METHODS: In 297 patients starting warfarin therapy,
      we assessed CYP2C9 genotypes (CYP2C9 *1, *2, and *3), VKORC1 haplotypes
      (designated A and non-A), clinical characteristics, response to therapy (as
      determined by the international normalized ratio [INR]), and bleeding events. The
      study outcomes were the time to the first INR within the therapeutic range, the
      time to the first INR of more than 4, the time above the therapeutic INR range,
      the INR response over time, and the warfarin dose requirement. RESULTS: As
      compared with patients with the non-A/non-A haplotype, patients with the A/A
      haplotype of VKORC1 had a decreased time to the first INR within the therapeutic
      range (P=0.02) and to the first INR of more than 4 (P=0.003). In contrast, the
      CYP2C9 genotype was not a significant predictor of the time to the first INR
      within the therapeutic range (P=0.57) but was a significant predictor of the time
      to the first INR of more than 4 (P=0.03). Both the CYP2C9 genotype and VKORC1
      haplotype had a significant influence on the required warfarin dose after the
      first 2 weeks of therapy. CONCLUSIONS: Initial variability in the INR response to
      warfarin was more strongly associated with genetic variability in the
      pharmacologic target of warfarin, VKORC1, than with CYP2C9.

PMID- 18322282
TI  - A Parkinsonian syndrome in methcathinone users and the role of manganese.
AB  - BACKGROUND: A distinctive extrapyramidal syndrome has been observed in
      intravenous methcathinone (ephedrone) users in Eastern Europe and Russia.
      METHODS: We studied 23 adults in Latvia who had extrapyramidal symptoms and who
      had injected methcathinone for a mean (+/-SD) of 6.7+/-5.1 years. The
      methcathinone was manufactured under home conditions by potassium permanganate
      oxidation of ephedrine or pseudoephedrine. All patients were positive for
      hepatitis C virus, and 20 were also positive for the human immunodeficiency virus
      (HIV). RESULTS: The patients reported that the onset of their first neurologic
      symptoms (gait disturbance in 20 and hypophonia in 3) occurred after a mean of
      5.8+/-4.5 years of methcathinone use. At the time of neurologic evaluation, all
      23 patients had gait disturbance and difficulty walking backward; 11 patients
      were falling daily, and 1 of these patients used a wheelchair. Twenty-one
      patients had hypophonic speech in addition to gait disturbance, and one of these
      patients was mute. No patient reported decline in cognitive function. T(1)
      weighted magnetic resonance imaging (MRI) showed symmetric hyperintensity in the
      globus pallidus and in the substantia nigra and innominata in all 10 active
      methcathinone users. Among the 13 former users (2 to 6 years had passed since the
      last use), lesser degrees of change in the MRI signal were noted. Whole-blood
      manganese levels (normal level, <209 nmol per liter) averaged 831 nmol per liter
      (range, 201 to 2102) in the active methcathinone users and 346 nmol per liter
      (range, 114 to 727) in former users. The neurologic deficits did not resolve
      after patients discontinued methcathinone use. CONCLUSIONS: Our observation of a
      distinctive extrapyramidal syndrome, changes in the MRI signal in the basal
      ganglia, and elevated blood manganese levels in methcathinone users suggests that
      manganese in the methcathinone solution causes a persistent neurologic disorder.

PMID- 18322283
TI  - Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen.
AB  - BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS-1) is a multiorgan
      autoimmune disorder caused by mutations in AIRE, the autoimmune regulator gene.
      Though recent studies concerning AIRE deficiency have begun to elucidate the
      molecular pathogenesis of organ-specific autoimmunity in patients with APS-1, the
      autoantigen responsible for hypoparathyroidism, a hallmark of APS-1 and its most
      common autoimmune endocrinopathy, has not yet been identified. METHODS: We
      performed immunoscreening of a human parathyroid complementary DNA library, using
      serum samples from patients with APS-1 and hypoparathyroidism, to identify
      patients with reactivity to the NACHT leucine-rich-repeat protein 5 (NALP5).
      Subsequently, serum samples from 87 patients with APS-1 and 293 controls,
      including patients with other autoimmune disorders, were used to determine the
      frequency and specificity of autoantibodies against NALP5. In addition, the
      expression of NALP5 was investigated in various tissues. RESULTS: NALP5-specific
      autoantibodies were detected in 49% of the patients with APS-1 and
      hypoparathyroidism but were absent in all patients with APS-1 but without
      hypoparathyroidism, in all patients with other autoimmune endocrine disorders,
      and in all healthy controls. NALP5 was predominantly expressed in the cytoplasm
      of parathyroid chief cells. CONCLUSIONS: NALP5 appears to be a tissue-specific
      autoantigen involved in hypoparathyroidism in patients with APS-1. Autoantibodies
      against NALP5 appear to be highly specific and may be diagnostic for this
      prominent component of APS-1.

PMID- 18322284
TI  - Clinical practice. Urinary stress incontinence in women.

PMID- 18322285
TI  - Acute pulmonary embolism.

PMID- 18322286
TI  - Images in clinical medicine. A medical mystery: epigastric pain.

PMID- 18322287
TI  - Clinical problem-solving. A key miscommunication--an 81-year-old woman presented
      to the emergency department with increasing abdominal distention, nausea, and
      vomiting.

PMID- 18322288
TI  - Pharmacogenomics--ready for prime time?

PMID- 18322289
TI  - Coordinating care--a perilous journey through the health care system.

PMID- 18322290
TI  - Eltrombopag in thrombocytopenia.

PMID- 18322291
TI  - Chitinase-like protein and asthma.

PMID- 18322292
TI  - Chemotherapy in unresectable head and neck cancer.

PMID- 18322293
TI  - Treatment of head and neck cancer.

PMID- 18322294
TI  - Graves' disease, thymus enlargement, and hypercalcemia.

PMID- 18322295
TI  - Primary ovarian insufficiency associated with imatinib therapy.

PMID- 18322296
TI  - The development and characteristics of a high-speed EELS mapping system for a
      dedicated STEM.
AB  - A new EELS (electron energy loss spectroscopy) real-time elemental mapping system
      has been developed for a dedicated scanning transmission electron microscope
      (STEM). The previous two-window-based jump-ratio system has been improved by a
      three-window-based system. It is shown here that the three-window imaging method
      has less artificial intensity in elemental maps than the two-window-based method.
      Using the new three-window system, the dependence of spatial resolution on the
      energy window width was studied experimentally and also compared with TEM-based
      EELS. Here it is shown experimentally that the spatial resolution of STEM-based
      EELS is independent of the energy window width in a range from 10 eV to 60 eV.

PMID- 18322297
TI  - Characterization of the charging effect in a ZrO2 sintered body by Ga ion beam
      irradiation.
AB  - The charging effect in a ZrO2 sintered body was investigated by using scanning
      ion microscope (SIM) images. In this study, we report interesting features caused
      by the charging effect in the ZrO2 sintered body during the Ga ion beam
      irradiation: a bright contrast with a distorted net shape appears around the
      positively charged specimen. From this feature in the SIM image, it is clarified
      that the Ga ion beam is strongly deflected and the wide area of the internal
      parts of the focused ion beam machine is irradiated by the Ga ion beam, depending
      on the extent to which the specimen is charged. We discuss the mechanism of the
      characteristic charging effect through observing SIM images by varying the
      intensity of the Ga ion beam.

PMID- 18322298
TI  - Human disease glycomics/proteome initiative (HGPI).

PMID- 18322299
TI  - A novel missense mutation in GALNT3 causing hyperostosis-hyperphosphataemia
      syndrome.
AB  - OBJECTIVE: Hyperostosis-hyperphosphataemia syndrome (HHS) is a rare hereditary
      disorder characterized by hyperphosphataemia, inappropriately normal or elevated
      1,25-dihydroxyvitamin D(3) and localized painful cortical hyperostosis. HHS was
      shown to be caused by inactivating mutations in GALNT3, encoding UDP-N-acetyl
      alpha-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc
      transferase; GALNT3). Herein, we sought to identify the genetic cause of
      hyperphosphataemia and tibial hyperostosis in a 19-year-old girl of Colombian
      origin. METHODS: Genomic DNA was extracted and sequencing analysis of the GALNT3
      and fibroblast growth factor 23 (FGF23) genes performed. Serum levels of intact
      and C-terminal FGF23 were measured using two different ELISA methods. RESULTS:
      Mutational analysis identified a novel homozygous missense mutation in exon 6 of
      GALNT3 (1584 G>A), leading to an amino acid shift from Arg to His at residue 438
      (R438H). The mutation was not found in over 200 control alleles or in any single
      nucleotide polymorphism databases. The R438 residue is highly conserved
      throughout species and in all known GalNAc-transferase family members. Modelling
      predicted the substitution deleterious for protein structure. Importantly, the
      phosphaturic factor FGF23 was differentially processed, as reflected by low
      intact (15 pg/ml) but high C-terminal (839 RU/ml) serum FGF23 levels.
      CONCLUSIONS: We report on the first missense mutation in GALNT3 giving rise to
      HHS, since previous GALNT3 mutations in HHS caused aberrant splicing or premature
      truncation of the protein. The R438H substitution likely abrogates GALNT3
      activity, in turn causing enhanced FGF23 degradation and subsequent
      hyperostosis/hyperphosphataemia.

PMID- 18322300
TI  - Impact of metformin and rosiglitazone treatment on glucose transporter 4 mRNA
      expression in women with polycystic ovary syndrome.
AB  - OBJECTIVE: The insulin-resistant state of the polycystic ovary syndrome (PCOS)
      was found to be associated with a decreased glucose transporter GLUT4 expression
      in the insulin target tissues. This study was performed to explore whether the
      well-known clinical, hormonal and metabolic efficacy of metformin or
      rosiglitazone treatment is reflected in the modulation of adipocyte GLUT4 mRNA
      expression in patients with PCOS. METHODS: We enrolled 35 women with PCOS. They
      received either metformin or rosiglitazone for 6 months. A history, blood samples
      for the measurement of androgens and s.c. adipose tissue samples were taken at
      baseline and end point. Quantification of GLUT4 mRNA expression in adipose tissue
      was performed using real-time quantitative PCR. Homeostasis model assessment
      (HOMA(IR)) score calculation was applied as a measure for insulin resistance
      (IR). RESULTS: GLUT4 mRNA expression in adipose tissue increased significantly in
      both groups (P<0.001). The increase was more pronounced in the rosiglitazone
      group (P=0.040). There was a statistically significant improvement of HOMA(IR) in
      both groups (P=0.008). After treatment, frequencies of menstrual bleeding were
      significantly higher (P<0.001) and serum total testosterone levels significantly
      lower in both groups (P=0.001). CONCLUSIONS: A 6-month therapy with insulin
      sensitizers resulted in marked improvement in adipose tissue GLUT4 mRNA
      expression in PCOS patients, rosiglitazone being more effective when compared
      with metformin. The augmentation of the insulin signal transduction was
      accompanied by a significant improvement of HOMA(IR), menstrual pattern and
      androgen profile.

PMID- 18322301
TI  - Characterization of the RET protooncogene transmembrane domain mutation S649L
      associated with nonaggressive medullary thyroid carcinoma.
AB  - CONTEXT: For rare and novel RET mutations associated with hereditary medullary
      thyroid carcinoma (MTC), clinical and functional studies are needed to classify
      the RET mutation into one of the three clinical risk groups. OBJECTIVE: We
      analyzed proliferative properties and clinical implications associated with the
      RET protooncogene transmembrane domain mutation S649L. DESIGN: The transforming
      potential and mitogenic properties of S649L mutation were investigated clinically
      and by evaluating kinase activity, cell proliferation, and colony formation.
      PATIENTS: Fifteen individuals from five kindreds were identified as carriers of a
      RET protooncogene mutation in exon 11 codon 649 (TCG(Ser)-->TTG(Leu)). In two out
      of five index patients, a second RET mutation (C634W or V804L) was detected.
      RESULTS: Eight gene carriers were operated on. Histology revealed MTC and C-cell
      hyperplasia in three index and three screening patients respectively. In all
      other gene carriers (aged 41-64 years), calcitonin levels were in the normal
      range, and pentagastrin-stimulated calcitonin levels were <100 pg/ml. Therefore,
      thyroidectomy had not yet been performed. In one index patient carrying the S649L
      mutation, hyperparathyroidism was confirmed histologically. RET S649L-expressing
      NIH3T3 cells exhibited a clear increase of phosphotyrosine and proliferation rate
      when compared with parental NIH3T3 cells but a significantly lower kinase
      activity and cell growth rate when compared with RET C634R-expressing cells. When
      compared with RET C634R, the S649L mutant showed moderate transforming potential
      with small-sized colonies. CONCLUSIONS: Our clinical and in vitro findings
      indicate that the transmembrane RET S649L mutation is associated with late-onset
      non-aggressive disease. Recommendations for prophylactic thyroidectomy should be
      individualized depending on stimulated calcitonin levels.

PMID- 18322302
TI  - Exploiting the antidiabetic properties of incretins to treat type 2 diabetes
      mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with
      inadequate glycemic control?
AB  - Type 2 diabetes mellitus is associated with progressive decreases in pancreatic
      beta-cell function. Most patients thus require increasingly intensive treatment,
      including oral combination therapies followed by insulin. Fear of hypoglycemia is
      a potential barrier to treatment adherence and glycemic control, while weight
      gain can exacerbate hyperglycemia or insulin resistance. Administration of
      insulin can roughly mimic physiologic insulin secretion but does not address
      underlying pathophysiology. Glucagon-like peptide 1 (GLP-1) is an incretin
      hormone released by the gut in response to meal intake that helps to maintain
      glucose homeostasis through coordinated effects on islet alpha- and beta-cells,
      inhibiting glucagon output, and stimulating insulin secretion in a glucose
      dependent manner. Biological effects of GLP-1 include slowing gastric emptying
      and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more
      suitable pharmacokinetic properties versus GLP-1) significantly lower hemoglobin
      A1c, body weight, and postprandial glucose excursions in humans and significantly
      improve beta-cell function in vivo (animal data). These novel incretin-based
      therapies offer the potential to reduce body weight or prevent weight gain,
      although the durability of these effects and their potential long-term benefits
      need to be studied further. This article reviews recent clinical trials comparing
      therapy with the incretin mimetic exenatide to insulin in patients with oral
      treatment failure, identifies factors consistent with the use of each treatment,
      and delineates areas for future research.

PMID- 18322303
TI  - Increased basal and pulsatile secretion of FSH and LH in young men with 47,XXY or
      46,XX karyotypes.
AB  - OBJECTIVE: The regulation of normal sexual maturation and reproductive function
      is dependent on a precise hormonal regulation at hypothalamic, pituitary, and
      gonadal levels. The aim of this study was to investigate the neuroendocrine
      integrity of the pituitary-gonadal axis in patients with primary testicular
      failure due to supernumerary X chromosomes. DESIGN: Cross-sectional study.
      METHODS: In this study, 7 untreated patients with primary gonadal insufficiency
      due to SRY-positive 46,XX (n=4) and 46,XXY karyotypes (n=3) aged 18.8 years and
      25 age-matched healthy controls participated. Reproductive hormones, testicular
      size, and overnight LH and FSH serum profiles and overnight urine LH and FSH
      excretion were determined. RESULTS: Basal LH and FSH secretion was elevated 6.3-
      and 25.4-fold respectively in the patients and the amount of LH and FSH secreted
      per burst were 2.0- and 6.6-fold elevated. We found significantly more LH but not
      FSH peaks per 24 h, as estimated by the Weibull lambda analysis. There was no
      difference between approximate entropy ratios or Weibull gamma analyses
      indicating comparable orderliness and regularity of LH and FSH secretion.
      Overnight urinary LH and FSH excretion was significantly elevated in patients
      compared with controls and correlated significantly with calculated total
      overnight LH and FSH secretion respectively, thus validating deconvolution.
      CONCLUSION: In this group of patients with severe hypergonadotropic hypogonadism
      due to a supernumerary X chromosome, higher basal, pulsatile, and total LH and
      FSH secretion were associated with significantly more LH peaks per 24 h in
      comparison with healthy controls. Thus, our data indicate that in patients with
      Klinefelter syndrome and XX male karyotypes the entire hypothalamic-pituitary
      gonadal axis has undergone functional changes.

PMID- 18322304
TI  - Association of an A/C single nucleotide polymorphism in programmed cell death
      ligand 1 gene with Graves' disease in Japanese patients.
AB  - OBJECTIVE: Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2)
      inhibit T-cell proliferation and activation. This inhibition down-regulates the
      immune responses. The association of a PD-L1 polymorphism with Graves' disease
      (GD) was studied. DESIGN: The association of an A/C polymorphism at position 8923
      in PD-L1 intron 4 with GD was studied. PATIENTS: The study included 327 GD
      patients and 192 controls, of which 252 GD patients were followed over 5-10
      years. MEASUREMENTS: PD-L1 intron 4 position 8923 A/C polymorphism was typed
      using the PCR-restriction fragment length polymorphism method. RESULTS: The A/C
      genotype frequencies were significantly different between GD patients and
      controls. The A/C and C/C frequencies were higher in GD patients than in
      controls. The A/A frequencies were lower in GD patients than in controls. C
      allele frequency was higher in GD patients than in controls. A total of 252 GD
      patients were followed over 5-10 years; 200 had discontinued antithyroid drugs
      (ATD) while 52 continued to take ATD. Of these 200, 176 continued to be in
      remission and 24 had relapsed into hyperthyroidism. Significant differences in
      the duration of positive TBII, positive thyroid-stimulating antibodies, and ATD
      treatment were noted between the patients in remission and those that had
      relapsed. Significant differences in the A- and C-allele frequencies were noted
      between the two. The C-allele frequency was higher in GD patients who did not
      achieve remission than in those who achieved remission. CONCLUSION: An A/C
      polymorphism at position 8923 in PD-L1 is associated with GD. The PD-L1
      polymorphism plays a role in GD development. GD patients with the C allele at
      position 8923 in PD-L1 gene had difficulty in achieving remission.

PMID- 18322305
TI  - Co-administration of CpG oligonucleotides and chenopodium album extract reverse
      IgG2a/IgG1 ratios and increase IFN-gamma and IL-10 productions in a murine model
      of asthma.
AB  - Asthma is a disorder of increasing severity and prevalence. Recent knowledge
      about the pathogenesis of asthma emphasizes its inflammatory nature. CpG
      oligonucleotides are a class of compounds containing motifs based on the cytosine
      guanine dinucleotides (CpG-ODNs). These motifs are suppressed in mammalian DNA.
      They induce inflammation in mammals characterized by the induction of T helper
      type 1 and regulatory responses. In this paper, the effect of CpG DNA co
      administration with a homemade Chenopodium album (Ch.a) extract in a murine model
      of asthma is reported for the first time. Balb/C mice were sensitized using Ch.a.
      pollen allergenic extract plus CpG-ODNs intraperitoneally and were challenged
      with aerosolized allergen. Results measured included IL-10 and IFN-gamma
      cytokines as well as IgG subclasses. For this, splenocytes from mice treated with
      CpG/Ag or Ag alone, were cultured in the presence of antigen. The results showed
      that CpG ODN administered at the time of Ch.a sensitization, effectively
      increased cytokines and IgG2a/IgG1 ratios compared with those in mice treated
      with antigen or with PBS alone(P<or= 0.001). Our experiments revealed that Ch.a.
      sensitization decreased IgG2a/IgG1 compared with non-sensitized mice (P<or=
      0.001), while CpG ODN/Ch.a reversed this ratio, indicating CpG potentials towards
      IgG2a subclass switching.We conclude that Co- administration of Ch.a. allergen
      and CpG ODN prevents the development of TH2-mediated response probably through
      the IL-10 regulatory effects. Thus, these components could be used with the other
      allergens in order to induce the prevention of inflammatory conditions. We
      suggest further studies are necessary to identify the potential effects of CpG
      ODNs administration in conjunction with other antigens prepared from the regional
      allergens in Iran. Taken together, we suppose that the results obtained in this
      study in animal models may be useful in human trials conducted by other
      investigators.

PMID- 18322306
TI  - Expression of HLA-G in the skin of patients with pemphigus vulgaris.
AB  - Studies on HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of
      basic and clinical significance. In the present study, the expression of HLA-G
      proteins in the human skin tissue sections of normal and autoimmune pemphigus
      vulgaris (PV) individuals were investigated using monoclonal antibodies. The
      antibodies recognized both membrane-bound and soluble isoforms of HLA-G. RT-PCR
      was performed to assess the patterns of HLA-G mRNA transcripts in the epidermal
      cells of PV and normal subjects. HLA-G expression could only be detected at
      transcriptional level in normal skin tissues. However cells derived from PV
      subjects expressed detectable HLA-G molecules at both transcriptional and
      translational levels. In addition, the RT-PCR patterns of HLA-G amplification
      revealed a reduction in HLA-G2 and an increase in HLA-G1 transcripts in epidermal
      cells of PV patients as compared to normal cells. These observations further
      support suggestions in the literature regarding the role of HLA-G in induction of
      tolerance in autoimmune individuals.

PMID- 18322307
TI  - Therapeutic effect of sodium alginate in experimental chronic ulcerative colitis.
AB  - The aim of this study was to test the therapeutic efficacy of sodium alginate in
      a rat model of trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel
      disease. This experiment was carried out using 77 Sprague-Dawley rats which were
      divided into six groups; normal, control, prophylactic, therapeutic and two
      experimental groups. Rats were sacrificed 1, 2, 3 and 6 weeks after colitis
      induction. Severity of colitis was graded macroscopically and assessed using
      serum and colonic mucosal cytokines and eicosanoids. Intrarectal TNBS (30 mg)
      produced a significant chronic ulcerative colitis. The lesions were most severe
      on day seven after TNBS instillation, and then declined, but lesions were still
      observed after six weeks. TNBS administration also significantly enhanced the
      serum and colonic mucosal cytokines (TNF-alpha and IL-6) and eicosanoids (LTB4
      and PGE2) levels, which paralleled with the severity of colitis. Low viscosity
      sodium alginate (LVA) solution as therapeutic agent was administered orally as
      drinking water at concentration of 0.5% (W/V) for six weeks. Results showed that
      pre-treatment (in prophylactic group) and treatment with LVA were significantly
      able to reduce colonic damage score, serum level and colonic mucosal production
      of TNF-alpha, IL-6, LTB4 and PGE2 in pre-treated and treated animals compared
      with non-treated controls. LVA therapy is able to suppress chronic ulcerative
      colitis in experimental model.

PMID- 18322308
TI  - Determination of HLA-B27 subtypes in Iranian patients with ankylosing
      spondylitis.
AB  - The human leukocyte antigen-B27 is one of the class I molecules of the major
      histocompatibility complex which is strongly associated with ankylosing
      spondylitis (AS). The strength of the disease association with B27 varies
      markedly among racial and ethnic populations. It is an allele family, which
      constitutes about 31 subtypes, with a considerable geographic and ethnic
      difference in distribution. It is important to know whether certain subtypes show
      any preferential association with AS. Because there is no report regarding HLA
      B27 subtypes in Iranian patients with AS, the main purpose of the present study
      was to assess the frequency of subtypes of human leukocyte antigen (HLA)-B27 in
      patients with ankylosing spondylitis in Iranian populationOne hundred and
      nineteen AS patients (82 HLA-B27 positive and 37 HLA-B27 negative) were selected
      for this study. HLA-B27 positive patients were screened by polymerase chain
      reaction amplification with sequence-specific primers (PCR-SSP) for B*27
      subtyping.The results of present study revealed that only two subtypes were
      detected in Iranian patients, including B*2705 (52 patients, 63.4%) and B*2702
      (30 patients, 36.6%). Our results showed a restricted number of HLA-B27 subtypes
      associated with AS in Iran and an elevated frequency of the B*2705 allele in
      these patients similar to other Euro-Caucasoid (Aryan) groups in the world.

PMID- 18322309
TI  - Respiratory resistance by impulse oscillometry in healthy Iranian children aged 5
      19 years.
AB  - The impulse oscillation system (IOS) measures respiratory impedance (Zrs) in
      terms of resistance (Rrs) and reactance (Xrs) at multiples of 5 Hz. These
      measurements can be used clinically to help diagnose and monitor respiratory
      disorders, independent of effort. There is, as yet, no information on reference
      values for IOS in Iranian adolescents.The predictive equation for resistance and
      impedance at 5 and 15 and 25 Hz, for the first time, in 509 Iranian adolescent
      subjects (265 boys (aged 6-19 years) and 253 girls (aged 5-19 years) were
      determined. Gender-specific linear prediction equations were developed by
      multiple regression analysis; with measuring (R5, R15, R25, X5, X15, X 25) as
      dependent variables regressed against age (A) and height (H).For both genders,
      age and height had negative effects on resistance, while age and height had a
      positive effect on reactance. The prediction equations for R5 and X5 are as
      follows: R5: -1.35x10(-5) x agex2.823 - 0.001 x height x1.022 + 0.547 for
      girlsX5: 1.78x10(-7)x age x1.08 + 0.002 height x4.150 - 0.539, for girls R5: 
      6.19x10(-7)x age x 3.820 - 6.78E-005 x height x1.651 + 0.691 for boysX5: 6.95x10(
      23) x age x16.226 + 0.004 height x 0.846- 0.430, for boys, respectively. Our
      results therefore provide an original frame of reference for R5, R15, R25, X5,
      X15, X25 in Iranian adolescents population, obtained from a standardized forced
      oscillation technique.

PMID- 18322310
TI  - Thyroid function and anti-thyroid antibodies in Iranian patients with type 1
      diabetes mellitus: influences of age and sex.
AB  - Type 1 diabetes mellitus is frequently associated with autoimmune thyroid disease
      (ATD).Genetic susceptibility for autoantibody formation in association with ATD
      and type 1 diabetes mellitus has been described with varying frequencies, but
      there is still debate about its prevailing situation in Iran. We have therefore
      investigated the prevalence of anti-thyroid peroxidase (anti-TPO) and anti
      thyroglubolin (Anti TG) antibodies in type 1 diabetic patients, and compared the
      effect of age and sex on the thyroid autoimmunity in patients with type 1
      diabetes mellitus in Iran.Ninety one subjects with type 1 diabetes mellitus and
      one hundred and sixty three unrelated normal controls under the age of thirty
      years were recruited for the detection of anti-TPO and anti-TG. Radio Immuno
      Assay and chemiluminescence methods were used for anti-TPO and anti-TG detection
      respectively.Among 91 type 1 diabetic patients, 36 (39.6%) were positive for anti
      TPO and 27(30%) were positive for antiTG. Anti-TPO antibodies were detected only
      in 6.7% of control group. Comparing with those without thyroid autoimmunity,
      there was a female preponderance for the type 1 diabetic patients with thyroid
      autoimmunity (female: male, 28:14 vs. 28:20 respectively). Among the type 1
      diabetic patients those with thyroid autoimmunity, tended to be older (p: 0.04)
      and to have higher TSH concentration (p: 0.03). Patients with high anti-TPO
      levels had longer duration of diabetes (P: 0.02).The presence of anti-TPO in
      39.6% of our type 1 diabetic patients comparing with 8.5% of normal subjects
      confirmed the strong association of ATD and type 1 diabetes mellitus.

PMID- 18322311
TI  - IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple
      sclerosis.
AB  - Different research groups have extensively studied the associations of cytokine
      gene polymorphisms in different diseases. The role of cytokines gene
      polymorphisms in multiple sclerosis (MS), as a chronic Immune-mediated
      neurodegenerative disease, has been previously reported in the various
      populations. For determining pro-inflammatory cytokine gene polymorphisms, 100
      relapsing remitting multiple sclerosis (RRMS) Iranian patients and 140 normal
      individuals as control enrolled in this study. DNA of each sample was extracted
      by a modified salting out method. Cytokine single gene nucleotide polymorphisms
      including IL-1alpha -889, IL-1beta (-511 and +3962), IL-1R pst1 1970, IL-1RA
      mspal 11100, and TNF-alpha (-308 and -238) were determined by using the PCR-SSP
      method. The results of our data indicate the decrease in frequency of IL-1alpha
      TC-889 genotype (p=0.002), IL-1beta TC +3962 genotype (p=0.004), IL-1R T pst1
      1970 allele (p= 0.0001), IL-1 RA TC Mspa1 11100 genotype (p=0.009), TNF-alpha A
      308 allele (p=0.0002) and AG genotype (p=0.00001) in the patients group versus
      normal subjects. On the other hand the frequency of IL-1alpha TT -889 genotype
      (p=0.028), IL-1R C pst1 1970 allele (p=0.0001) and CC genotype (p=0.00006),
      TNFalpha G -308 allele (p=0.0002) and GG genotype (p=0.000001) decreased
      significantly in the patients versus normal subjects.These results suggest that
      polymorphic variations of these pro-inflammatory cytokines may play an important
      role in susceptibility of Iranian multiple sclerosis patients.

PMID- 18322312
TI  - Onychomadesis in a patient with immunoglobulin class switch recombination
      deficiency.
AB  - Immunoglobulin class switch recombination deficiencies (Ig CSR deficiencies) or
      Hyper IgM syndromes (HIGM) are a group of primary immunodeficiency diseases,
      characterized by defective CD40 signaling of B cells, resulting in reduced CSR
      and somatic hypermutation. The affected patients are characterized by low serum
      levels of IgG and IgA, and normal or elevated levels of IgM, which lead to an
      increased susceptibility to infections. We describe a 3 year-old boy with
      frequent bacterial infections of the skin and respiratory tract, mucosal ulcers,
      and diarrhea. He experienced onychomadesis of both fingernails and toenails
      during a recent bacterial infection. Quantitative immunoglobulin measurements
      revealed high levels of serum IgM and very low levels of IgG, IgA, and IgE.
      Clinical and immunologic studies supported the diagnosis of HIGM. Exclusion of
      CD40L, CD40, AID and UNG genes by molecular analysis in this patient may suggest
      a new form of selective CSR deficiency.

PMID- 18322313
TI  - Role of Chlamydia pneumoniae infection in asthma in Northeast of Iran.
AB  - The role of Chlamydia pneumoniae in asthma has drawn much attention in recent
      years. In this study we assessed the prevalence of C. pneumoniae infections in
      patients with chronic stable and acute exacerbation of asthma and compared it
      with normal population. Twenty adult patients with chronic stable asthma and 21
      patients with acute exacerbations of asthma and 41 matched control subjects were
      studied for presence of C. pneumoniae using cell culture. This study suggests
      that positive results of C. pneumoniae culture are associated with both chronic
      stable and acute exacerbation of asthma. It could be concluded that C. pneumoniae
      is a risk factor for either development or exacerbation of asthma.

PMID- 18322314
TI  - Synthetic aenigmatite analog Na2(Mn5.26Na0.74)Ge6O20: structure and crystal
      chemical considerations.
AB  - Disodium hexamanganese(II,III) germanate is the first aenigmatite-type compound
      with significant amounts of manganese. Na(2)(Mn(5.26)Na(0.74))Ge(6)O(20) is
      triclinic and contains two different Na positions, six Ge positions and 20 O
      positions (all with site symmetry 1 on general position 2i of space group P1).
      Five out of the seven M positions are also on general position 2i, while the
      remaining two have site symmetry 1 (Wyckoff positions 1f and 1c). The structure
      can be described in terms of two different layers, A and B, stacked along the
      [011] direction. Layer A contains pyroxene-like chains and isolated octahedra,
      while layer B is built up by slabs of edge-sharing octahedra connected to one
      another by bands of Na polyhedra. The GeO(4) tetrahedra show slight polyhedral
      distortion and are among the most regular found so far in germanate compounds.
      The M sites of layer A are occupied by highly charged (trivalent) cations, while
      in layer B a central pyroxene-like zigzag chain can be identified, which contains
      divalent (or low-charged) cations. This applies to the aenigmatite-type compounds
      in general and to the title compound in particular.

PMID- 18322315
TI  - The diphyllosilicate Rb2(VO)2[Si8O19].
AB  - Dirubidium divanadyl phyllooctasilicate, Rb(2)(VO)(2)[Si(8)O(19)], is the first
      known anhydrous diphyllosilicate containing V(IV). The structure consists of
      silicate double layers which are separated by [V(2)O(8)](8-) dimers and is
      related to that of the compounds A(2)Cu(2)[Si(8)O(19)] (A = Rb or Cs), although
      the title compound crystallizes in a noncentrosymmetric orthorhombic space group.
      The silicate double layers contain four tetrahedrally coordinated Si sites in
      general positions and 12 O sites, nine in general positions and the other three
      on mirror planes. The vanadyl dimers have two square-pyramidally coordinated V
      sites (site symmetry m). There are two different 10- and 12-fold coordinated Rb
      sites with site symmetry m, one of which is a split position located between the
      dimers in the interlayer space, while the other is in a channel within the
      silicate layer.

PMID- 18322316
TI  - The disordered cluster compound CaMo5(Mo0.38Ti0.62)O10.
AB  - The title compound, calcium pentamolybdenum titanium decaoxide, is isomorphous
      with the AMo(5)(Ti(0.7)Mo(0.3))O(10) (A = Sr and Eu) compounds. The smaller size
      of calcium induces a higher molybdenum content on the capping sites of the
      bioctahedral Mo(10) clusters, leading to more Mo(11) and Mo(12) clusters in the
      crystal structure. The oxygen framework derives from the stacking of close-packed
      layers along the a direction in the ...ABAC... sequence. The Ca(2+) ions occupy
      large cavities which result from the fusion of two cubooctahedra and are
      surrounded by ten O atoms. The Ti(4+) ion is octahedrally coordinated by the O
      atoms.

PMID- 18322317
TI  - Poly[[diaquabis[mu(2)-2-(4-pyridinio)propane-1,3-dionato-kappa2O:O']cobalt(II)]
      dinitrate].
AB  - The title compound, {[Co(C(8)H(7)NO(2))(2)(H(2)O)(2)](NO(3))(2)}(n), is the first
      d-metal ion complex involving bidentate bridging of a beta-dialdehyde group. The
      Co(2+) ion is situated on an inversion centre and adopts an octahedral
      coordination with four equatorial aldehyde O atoms [Co-O = 2.0910 (14) and 2.1083
      (14) A] and two axial aqua ligands [Co-O = 2.0631 (13) A]. The title compound has
      a two-dimensional square-grid framework structure supported by propane-1,3
      dionate O:O'-bridges between the metal ions. The organic ligand itself possesses
      a zwitterionic structure, involving conjugated anionic propane-1,3-dionate and
      cationic pyridinium fragments. Hydrogen bonding between coordinated water
      molecules, the pyridinium NH group and the nitrate anions [O...O = 2.749 (2) and
      2.766 (3) A, and N...O = 2.864 (3) A] is essential for the crystal packing.

PMID- 18322318
TI  - {Mu-N,N'-bis[2-(dimethylamino)ethyl]oxamidato(2-)
      kappa(6)N,N',O':N'',N''',O}bis[(2,2'-bipyridine-kappa2N,N')copper(II)]
      bis(perchlorate).
AB  - In the crystal structure of the title complex,
      [Cu(2)(C(10)H(20)N(4)O(2))(C(10)H(8)N(2))(2)](ClO(4))(2), the deprotonated
      dmaeoxd(2-) ligand {H(2)dmaeoxd is N,N'-bis[2-(dimethylamino)ethyl]oxamide}
      occupies an inversion centre at the mid-point of the central C-C bond and is thus
      in a trans conformation. The two Cu(II) atoms are located in slightly distorted
      square-based pyramidal environments. The binuclear units interact with each other
      via pi-pi interactions to form a one-dimensional chain extending in the c
      direction.

PMID- 18322319
TI  - Tris(1,10-phenanthroline-kappa2N,N')cobalt(III) tris(trifluoromethanesulfonate)
      dihydrate.
AB  - The title compound, [Co(C(12)H(8)N(2))(3)](CF(3)SO(3))(3) x 2 H(2)O, crystallizes
      to form infinite chains of complex cations that are connected through offset face
      to-face and edge-to-face interactions between their phenanthroline ligands. The
      chains are themselves interconnected through weak offset face-to-face ligand
      interactions. The three trifluoromethanesulfonate anions of the asymmetric unit
      are connected with one another through the two water molecules by hydrogen bonds.
      One of the trifluoromethanesulfonate anions is described by a disorder over three
      positions, with occupancies of 0.35, 0.35 and 0.3 in the refined model.

PMID- 18322320
TI  - Positional disorder manifested as compositional in a pseudo-C2-symmetrical Pd
      complex.
AB  - The title compound {2-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-ylmethyl]-6-(3,5
      dimethyl-1H-pyrazol-1-ylmethyl)pyridine}methylpalladium(II) tetrakis[3,5
      bis(trifluoromethyl)phenyl]borate, [Pd(C(18)H(18)F(6)N(5))][B(C(8)H(3)F(6))(4)],
      crystallizes as discrete cations and anions. The cation possesses a pseudo
      twofold axis about which positional disorder of the tridentate ligand is
      exhibited. The four substituents on the two pyrazole rings exhibit CH(3)/CF(3)
      disorder, while all other atoms are ordered. Thus, this disorder can be
      conveniently described 'locally' as compositional, while 'globally' for the
      entire tridentate ligand it is positional. The anion also exhibits typical
      rotational positional disorder in three of the CF(3) groups. All disordered CF(3)
      groups were modeled with idealized C(3v) geometry.

PMID- 18322321
TI  - Copper(II) and cadmium(II) isothiocyanate coordination polymers with 4,4'-bi
      1,2,4-triazole.
AB  - The coordination polymers catena-poly[[[(4,4'-bi-1,2,4-triazole
      kappaN(1))bis(thiocyanato-kappaN)copper(II)]-mu-4,4'-bi-1,2,4-triazole
      kappa(2)N(1):N(1')] dihydrate], {[Cu(NCS)(2)(C(4)H(4)N(6))(2)].2H(2)O}(n), (I),
      and poly[tetrakis(mu-4,4'-bi-1,2,4-triazole-kappa(2)N(1):N(1'))bis(mu-thiocyanato
      kappa(2)N:S)tetrakis(thiocyanato-kappaN)tricadmium(II)],
      [Cd(3)(NCS)(6)(C(4)H(4)N(6))(4)](n), (II), exhibit chain and two-dimensional
      layer structures, respectively. The differentiation of the Lewis acidic nature of
      Cu(II) and Cd(II) has an influence on the coordination modes of the triazole and
      thiocyanate ligands, leading to topologically different polymeric motifs. In (I),
      copper ions are linked by bitriazole N:N'-bridges into zigzag chains and the
      tetragonal-pyramidal CuN(5) environment is composed of two thiocyanate N atoms
      and three triazole N atoms [basal Cu-N = 1.9530 (18)-2.0390 (14) A and apical Cu
      N = 2.2637 (15) A]. The structure of (II) contains two types of
      crystallographically unique Cd(II) atoms. One type lies on an inversion center in
      a distorted CdN(6) octahedral environment, with bitriazole ligands in the
      equatorial plane and terminal isothiocyanate N atoms in the axial positions. The
      other type lies on a general position and forms centrosymmetric binuclear
      [Cd(2)(mu-NCS-kappa(2)N:S)(2)(NCS)(2)] units (tetragonal-pyramidal CdN(4)S
      coordination). N:N'-Bridging bitriazole ligands link the Cd centers into a flat
      (4,4)-network.

PMID- 18322322
TI  - Mu2-acetato-kappa(2)O:O'-tris(mu2-ferrocenecarboxylato-kappa(2)O:O')bis[(N,N
      dimethylformamide-kappaO)copper(II)].
AB  - The title compound,
      [Cu(2)Fe(3)(C(5)H(5))(3)(C(2)H(3)O(2))(C(6)H(4)O(2))(3)(C(3)H(7)NO)(2)], belongs
      to the classic dimeric paddle-wheel structure type. It is an unusual example in
      that it contains two different carboxylate groups, viz. ferrocenecarboxylate and
      acetate. With three ferrocenecarboxylate groups and only one acetate group
      bridging the two Cu centres, a noncentrosymmetric molecular arrangement results.

PMID- 18322323
TI  - Supramolecular interaction patterns in the zinc(II) dichloride and tin(IV)
      tetrachloride complexes with dipyrido[f,h]quinoxaline-6,7-dicarbonitrile.
AB  - This study characterizes the supramolecular synthons that dominate the
      intermolecular organization of the title compounds, namely
      dichloridobis(dipyrido[f,h]quinoxaline-6,7-dicarbonitrile)zinc(II),
      [ZnCl(2)(C(16)H(6)N(6))(2)], (I), and tetrachlorido(dipyrido[f,h]quinoxaline-6,7
      dicarbonitrile)tin(IV), [SnCl(4)(C(16)H(6)N(6))], (II), in their respective
      crystal structures. Molecules of (I) are located on 2(b) axes of rotational
      symmetry. Their crystal packing is stabilized mostly by pi-pi stacking and dipole
      dipole attractions between the organic ligand fragments of inversion-related
      neighbouring species, as well as by weak intermolecular C-H...N hydrogen bonds.
      On the other hand, Cl...pi and N...pi interactions seem to direct the crystal
      packing in (II), which is unusual in the sense that its aromatic fragments are
      not involved in pi-pi stacking. Molecules of (II) are located on m(b) planes of
      mirror symmetry. This study confirms the diverse structural chemistry of this
      organic ligand, which can be involved in a wide range of supramolecular
      interactions. These include effective coordination to various metal ions via the
      phenathroline N-atom sites, pi-pi stacking and pi...halogen contacts through its
      extended pi-system, and hydrogen bonding and N...pi interactions through its
      nitrile groups. The competing natures of the latter make it difficult to predict
      a priori the preferred supramolecular motif that may form in a given structure.

PMID- 18322324
TI  - Dihydroxyacetone (DHA) monomer complexes with CaBr2 and CdCl2.
AB  - Two hydrated complexes of monomeric dihydroxyacetone (DHA; the simplest ketose),
      viz. the calcium bromide complex bis(mu
      dihydroxyacetone)bis[tetraaquacalcium(II)] tetrabromide (isomorphous with the
      chloride compound reported previously), [Ca(2)(C(3)H(6)O(3))(2)(H(2)O)(8)]Br(4),
      (2e), and the cadmium chloride complex poly[[bis(mu
      dihydroxyacetone)bis[bis(dihydroxyacetone)cadmium(II)]] [diaquatetradeca-mu
      chlorido-dichloridohexacadmium(II)] tetrahydrate],
      {[Cd(2)(C(3)H(6)O(3))(6)][Cd(6)Cl(16)(H(2)O)(2)] x 4 H(2)O}(n), (2f), are
      described. The Ca(2+) or Cd(2+) ions are bridged by the carbonyl O atoms from two
      DHA molecules to form centrosymmetric dimers, with Ca...Ca distances of 4.334 (2)
      and 4.300 (2) A in (2e), and a Cd...Cd distance of 4.195 (1) A in (2f). Almost
      identical in shape, the eight-coordinate polyhedra of the Ca(2+) and Cd(2+) ions
      are composed of 2n O atoms from n DHA molecules [n = 2 in (2e) and n = 4 in (2f)]
      and are completed by four water molecules in (2e). DHA molecules chelate the
      cations via both the hydroxyl and carbonyl groups and exist in an extended
      conformation, with both hydroxyl groups being synperiplanar to the carbonyl O
      atom. The crystal structures are stabilized by similar extensive O-H...X (X = Cl
      or Br) and O-H...O hydrogen-bond networks involving all hydroxyl groups and the
      water molecules.

PMID- 18322325
TI  - Poly[mu-2-aminopyrazine-kappa2N1:N4-mu-cyanido-copper(I)]: a three-dimensional
      network from laboratory powder diffraction data.
AB  - In the title compound, [Cu(CN)(C(4)H(5)N(3))](n) or [Cu(mu-CN)(mu-PyzNH(2))](n)
      (PyzNH(2) is 2-aminopyrazine), the Cu(I) center is tetrahedrally coordinated by
      two cyanide and two PyzNH(2) ligands. The Cu(I)-cyano links give rise to [Cu
      CN](infinity) chains running along the c axis, which are bridged by bidentate
      PyzNH(2) ligands. The three-dimensional framework can be described as being
      formed by two interpenetrated three-dimensional honeycomb-like networks, both
      made of 26-membered rings of composition [Cu(6)(mu-CN)(2)(mu-PyzNH(2))(4)].

PMID- 18322326
TI  - A square-planar Ni(II) complex with an asymmetric coordination of a novel
      polynucleative 2,6-diacetylpyridine bis{[2-(hydroxyimino)propanoyl]hydrazone}
      ligand.
AB  - The title compound, (2,6-diacetylpyridine bis{[2
      (hydroxyimino)propanoyl]hydrazone}(2-))nickel(II) dimethyl sulfoxide solvate
      monohydrate, [Ni(C(15)H(17)N(7)O(4))] x C(2)H(6)OS x H(2)O, represents the first
      example of square-planar N(4) coordination via N atoms with four different
      functions, namely amide, azomethine, hydroxyimino and pyridine. The coordination
      polyhedron of the central Ni atom has a slightly distorted square-planar
      geometry. The 2,6-diacetylpyridine bis{[2-(hydroxyimino)propanoyl]hydrazone}
      ligand forms one six- and two five-membered chelate rings, and a pseudo-chelate
      ring through an intramolecular hydrogen bond with an amide group as donor and a
      deprotonated hydroxyimino group as acceptor, resulting in a pseudomacrocyclic
      arrangement.

PMID- 18322327
TI  - Adducts of bis(acetylacetonato)zinc(II) with 1,10-phenanthroline and 2,2'
      bipyridine.
AB  - In each of the zinc(II) complexes bis(acetylacetonato-kappa(2)O,O')(1,10
      phenanthroline-kappa(2)N,N')zinc(II), [Zn(C(5)H(7)O(2))(2)(C(12)H(8)N(2))], (I),
      and bis(acetylacetonato-kappa(2)O,O')(2,2'-bipyridine-kappa(2)N,N')zinc(II),
      [Zn(C(5)H(7)O(2))(2)(C(10)H(8)N(2))], (II), the metal center has a distorted
      octahedral coordination geometry. Compound (I) has crystallographically imposed
      twofold symmetry, with Z' = 0.5. The presence of a rigid phenanthroline group
      precludes intramolecular hydrogen bonding, whereas the rather flexible bipyridyl
      ligand is twisted to form an intramolecular C-H...O interaction [the chelated
      bipyridyl ligand is nonplanar, with the pyridyl rings inclined at an angle of
      13.4 (1) degrees]. The two metal complexes are linked by dissimilar C-H...O
      interactions into one-dimensional chains. The present study demonstrates the
      distinct effects of two commonly used ligands, viz. 1,10-phenanthroline and 2,2'
      bipyridine, on the structures of metal complexes and their assembly.

PMID- 18322328
TI  - syn-Tri-mu-chlorido-bis{[(R,R)/(S,S)-2,2'-bis(diphenylphosphino)-1,1'
      biphenyl]hydridoiridium(III)} tetrafluoridoborate dichloromethane disolvate.
AB  - In the structure of the title compound, [Ir(2)Cl(3)H(2)(C(36)H(28)P(2))(2)]BF(4)
      x 2 CH(2)Cl(2), the bimetallic cation features a confacial bioctahedral structure
      that is held together by three bridging chloride ions and is very close to C(2)
      symmetric. The hydrides are in a syn orientation (trans to the same halide
      bridge), and the chelating bis(phosphine) atropisomers display a racemic
      (R,R)/(S,S) configuration. Because of the high trans-bond-weakening influence of
      the hydride ligands, the Ir-Cl bonds trans to Ir-H [2.5262 (7) and 2.5365 (7) A]
      are significantly longer than those opposite the Ir-P linkages [2.4287 (7)-2.4672
      (8) A]. The Ir-P distances vary between 2.2464 (9) and 2.2565 (8) A. This study
      illustrates the usefulness of sterically demanding biaryl-based P(2) ligands in
      the synthesis of halide-bridged Ir(2) complexes, which are valuable precursors of
      versatile catalysts for homogeneous C=O hydrogenation.

PMID- 18322329
TI  - Polymorphs of gabapentin.
AB  - Gabapentin [or 1-(aminomethyl)cyclohexaneacetic acid], C(9)H(17)NO(2), exists as
      a zwitterion [1-(ammoniomethyl)cyclohexaneacetate] in the solid state. The
      crystal structures and bonding networks of two new monoclinic polymorphs (beta
      gabapentin and gamma-gabapentin) are studied and compared with a previously
      reported gabapentin polymorph [alpha-gabapentin: Ibers (2001). Acta Cryst. C57,
      641-643]. All three polymorphs have extensive networks of hydrogen bonds between
      the NH(3)(+) and COO(-) groups of neighbouring molecules. In beta-gabapentin,
      there is an additional weak intramolecular hydrogen bond.

PMID- 18322330
TI  - 3,4,6-Trichloro-5-cyano-2-hydroxybenzamide.
AB  - The title compound, C(8)H(3)Cl(3)N(2)O(2), forms crystals in which hydrogen
      bonding and Cl...N interactions appear to be equally important to the structure.
      The molecules form ribbons held together alternately by cyclic (CONH)(2) and
      cyclic (ClCCC[triple-bond]N)(2) interactions. The ribbons assemble into layers
      through Cl...Cl interactions. The layers are held together by NH...N[triple
      bond]C hydrogen bonds, as well as by pi-pi interactions.

PMID- 18322331
TI  - The complex packing pattern of cis-1,2-dimethylcyclobutane-1,2-diol.
AB  - cis-1,2-Dimethylcyclobutane-1,2-diol, C(6)H(12)O(2), crystallizes with five
      molecules in the asymmetric unit. Of these, two molecules are the building blocks
      of columns with a complex hydrogen-bonding pattern in their hydrophilic core. The
      walls of the columns are formed by the lipophilic parts of the molecules. The
      remaining three molecules of the asymmetric unit build columns with a less
      complex hydrogen-bonding system. In terms of co-operativity, the most significant
      feature is the formation of homodromic rings of six hydroxy functions.

PMID- 18322332
TI  - 1-(Diaminomethylene)thiourea: a tautomer of 2-imino-4-thiobiuret.
AB  - Crystals of the title compound, C(2)H(6)N(4)S, are built up from nonplanar 1
      (diaminomethylene)thiourea molecules. Pairs of molecules related by inversion are
      linked by N-H...N hydrogen bonds to form dimeric units, and weak N-H...S
      interactions link these dimeric units into a three-dimensional framework.

PMID- 18322333
TI  - 3,3'-Dinitro-2,2'-dithiodipyridine.
AB  - In the title compound, C(10)H(6)N(4)O(4)S(2), (I), the molecule has a centre of
      inversion. The structure is a positional isomer of 5,5'-dinitro-2,2'
      dithiodipyridine [Brito, Mundaca, Cardenas, Lopez-Rodriguez & Vargas (2007). Acta
      Cryst. E63, o3351-o3352], (II). The 3-nitropyridine fragment of (I) shows
      excellent agreement with the bonding geometries of (II). The most obvious
      differences between them are in the S-S bond length [2.1167 (12) A in (I) and
      2.0719 (11) A in (II)], and in the C-C(ipso)-N(ring) [119.8 (2) degrees in (I)
      and 123.9 (3) degrees in (II)] and S-C-C [122.62 (18) degrees in (I) and 116.0
      (2) degrees in (II)] angles. The crystal structure of (I) has an intramolecular C
      H...O interaction, with an H...O distance of 2.40 (3) A, whereas this kind of
      interaction is not evident in (II). The molecules of (I) are linked into
      centrosymmetric R(4)(4)(30) motifs by a C-H...O interaction. There are no
      aromatic pi-pi stacking and no C-H...pi(arene) interactions. Compound (I) can be
      used as a nucleophilic tecton in self-assembly reactions with metal centres of
      varying lability.

PMID- 18322334
TI  - Rosiglitazone maleate 0.25-hydrate: a pseudopolymorphic form.
AB  - The present 0.25-hydrated form of rosiglitazone maleate [systematic name: (+/-)-2
      ({2-[2,4-dioxo-1,3-thiazolidin-5-ylmethyl)phenoxy]ethyl}methylamino)pyridinium
      maleate 0.25-hydrate], C(18)H(20)N(3)O(3)S(+) x C(4)H(3)O(4)(-) x 0.25 H(2)O, is
      a racemate with two independent moieties in the unit cell. Although the cation
      geometry does not differ substantially from that in the previously reported
      hydrochloride, the packing is quite different, the main feature being the
      formation of hydrogen-bonded tetramers, linked head-to-tail into weakly
      interacting chains.

PMID- 18322335
TI  - The 1:1 proton-transfer compounds of 4-(phenyldiazenyl)aniline (aniline yellow)
      with 3-nitrophthalic, 4-nitrophthalic and 5-nitroisophthalic acids.
AB  - The structures of the anhydrous 1:1 proton-transfer compounds of the dye
      precursor aniline yellow [4-(phenyldiazenyl)aniline], namely isomeric 4
      (phenyldiazenyl)anilinium 2-carboxy-6-nitrobenzoate, C(12)H(12)N(3)(+) x
      C(8)H(4)NO(6)(-), (I), and 4-(phenyldiazenyl)anilinium 2-carboxy-4-nitrobenzoate,
      C(12)H(12)N(3)(+) x C(8)H(4)NO(6)(-), (II), and 4-(phenyldiazenyl)anilinium 3
      carboxy-5-nitrobenzoate monohydrate, C(12)H(12)N(3)(+) x C(8)H(4)NO(6)(-) x
      H(2)O, (III), have been determined at 130 K. In (I) the cation has longitudinal
      rotational disorder. All three compounds have substructures comprising backbones
      formed through strong head-to-tail carboxyl-carboxylate hydrogen-bond
      interactions [graph set C(7) in (I) and (II), and C(8) in (III)]. Two-dimensional
      sheet structures are formed in all three compounds by the incorporation of the 4
      (phenyldiazenyl)anilinium cations into the substructures, including, in the cases
      of (I) and (II), infinite H-N-H to carboxylate O-C-O group interactions [graph
      set C(6)], and in the case of (III), bridging through the water molecule of
      solvation. The peripheral alternating aromatic ring residues of both cations and
      anions give only weakly pi-interactive step features which lie between the
      sheets.

PMID- 18322336
TI  - 13-cis-Beta,beta-carotene and 15-cis-beta,beta-carotene.
AB  - 13-cis-Beta,beta-carotene, C(40)H(56), crystallizes with a complete molecule in
      the asymmetric unit, whereas 15-cis-beta,beta-carotene, also C(40)H(56), has
      twofold symmetry about an axis through the central bond of the polyene chain. The
      polyene methyl groups are arranged on one side of the polyene chains for each
      molecule and the 6-s-cis beta end groups, with the cyclohexene rings in half
      chair conformations, are twisted out of the planes of the polyene chains by
      angles ranging from 41.37 (17) to 52.2 (4) degrees. The molecules in each
      structure pack so that the arms of one occupy the cleft of the next, and there is
      significant pi-pi stacking of the almost-parallel polyene chains of the 15-cis
      isomer, which approach at distances of 3.319 (1)-3.591 (1) A.

PMID- 18322337
TI  - Vinyl sulfones.
AB  - Four neutral vinyl sulfones, two of which are paired with phosphonate groups, are
      described. The compounds are diisopropyl (2
      phenylethenylsulfonylmethyl)phosphonate, C(15)H(23)O(5)PS, (I), diisopropyl {[2
      (7-methoxy-1,3-benzodioxol-5-yl)ethenylsulfonyl]methylsulfonylmethyl}phosphonate,
      C(18)H(27)O(10)PS(2), (II), bis(trans-2-phenylethenyl) sulfone, C(16)H(14)O(2)S,
      (III), and bis(trans-2-phenylethenylsulfonyl)methane, C(17)H(16)O(4)S(2), (IV).
      Their structures can be considered as highly functionalized mimics of mono-, di-
      and triphosphates. These phosphate isosteres are currently of interest as agents
      for enzyme inhibition in both cancer and HIV therapy. All except one of the
      compounds has Z' > 1. The lone exception is (IV), a disulfone with twofold
      crystallographic symmetry. Geometrically, the sulfone functionality is found to
      be a good mimic for phosphate. The principal effect of the vinyl group is to
      shorten the S-C(vinyl) distance relative to the S-CH(2) distance by ca 0.05 A.
      The S-C-S and S-C-P backbones resemble the P-O-P backbone but are not identical
      because the S-C and P-C distances are longer than the P-O distance and the S-C-S
      and S-C-P angles are more acute than the P-O-P angle. No prior crystal structures
      of comparable compounds have been published.

PMID- 18322338
TI  - Cocrystal of cis- and trans-N-phenylformamide.
AB  - N-Phenylformamide, C(7)H(7)NO, crystallizes with two molecules in the asymmetric
      unit which have different conformations of the formylamino group, one being cis
      and the other trans. This is the first example of an arylformamide crystal
      containing both conformational isomers and it may thus be considered a cocrystal
      of the two conformers. The two molecules in the unit cell are linked through N
      H...O hydrogen bonding to two other molecules, thereby forming hydrogen-bonded
      tetramers within the crystal structure.

PMID- 18322339
TI  - Cyclopentadecanone 2,4-dinitrophenylhydrazone.
AB  - In the title compound, C(21)H(32)N(4)O(4), no disorder is present in the 15
      membered hydrocarbon ring, which exists in an unsymmetrical quinquangular [12345]
      conformation. The 2,4-dinitrophenylhydrazone group is approximately perpendicular
      to the C(15) ring, with a dihedral angle of 84.66 (1) degrees between their best
      planes.

PMID- 18322340
TI  - Assembly of a two-dimensional layer structure with 1,4-bis(1H-benzimidazol-1
      ylmethyl)benzene dihydrate via hydrogen bonds and pi-pi interactions.
AB  - In the title compound, C(22)H(18)N(4).2H(2)O, the organic fragment lies across a
      centre of inversion in the P2(1)/n space group. The water molecules form C(2)
      type hydrogen-bonded chains which are linked to the 1,4-bis(1H-benzimidazol-1
      ylmethyl)benzene molecules through O-H...N hydrogen bonds, forming sheets
      reinforced by pi-pi stacking interactions between the aromatic rings within the
      layers.

PMID- 18322341
TI  - Hydrogen-bonded ribbons in ethyl (E)-3-[2-amino-4,6-bis(dimethylamino)pyrimidin-5
      yl]-2-cyanoacrylate and 2-[(2-amino-4,6-di-1-piperidylpyrimidin-5
      yl)methylene]malononitrile.
AB  - The pyrimidine rings in ethyl (E)-3-[2-amino-4,6-bis(dimethylamino)pyrimidin-5
      yl]-2-cyanoacrylate, C(14)H(20)N(6)O(2), (I), and 2-[(2-amino-4,6-di-1
      piperidylpyrimidin-5-yl)methylene]malononitrile, C(18)H(23)N(7), (II), which
      crystallizes with Z' = 2 in the P1 space group, are both nonplanar with boat
      conformations. The molecules of (I) are linked by a combination of N-H...N and N
      H...O hydrogen bonds into chains of edge-fused R(2)(2)(8) and R(4)(4)(20) rings,
      while the two independent molecules in (II) are linked by four N-H...N hydrogen
      bonds into chains of edge-fused R(2)(2)(8) and R(2)(2)(20) rings. This study
      illustrates both the readiness with which highly-substituted pyrimidine rings can
      be distorted from planarity and the significant differences between the
      supramolecular aggregation in two rather similar compounds.

PMID- 18322342
TI  - Four products from the cyanoacetylation of pyrimidines: hydrogen-bonded dimers,
      pi-stacked hydrogen-bonded chains and hydrogen-bonded chains of edge-fused rings.
AB  - The molecules of 2-[6-amino-3-methyl-2-(methylsulfanyl)-4-oxo-3,4
      dihydropyrimidin-5-ylcarbonyl]acetonitrile, C(9)H(10)N(4)O(2)S, (I), are linked
      in pairs by N-H...O hydrogen bonds to form cyclic centrosymmetric R(2)(2)(4)
      dimers. Similar dimers formed by 2-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4
      tetrahydropyrimidin-5-ylcarbonyl)acetonitrile, C(9)H(10)N(4)O(3), (II), are
      reinforced by paired N-H...N hydrogen bonds and linked into chains of rings by C
      H...O hydrogen bonds. The molecules of 2-cyano-N-[6-methoxy-2
      (methylsulfanyl)pyrimidin-4-yl]acetamide, C(9)H(10)N(4)O(2)S, (III), are linked
      into simple C(6) chains by an N-H...N hydrogen bond, and the chains are weakly
      linked into sheets by a pi-pi stacking interaction. A combination of one two
      centre N-H...N hydrogen bond and one three-centre C-H...(N,O) hydrogen bond links
      the molecules of 2-cyano-N-[6-chloro-2-(methylsulfanyl)pyrimidin-4-yl]acetamide,
      C(8)H(7)ClN(4)OS, (IV), into a chain of alternating edge-fused R(2)(1)(6) and
      R(1)(2)(6) rings. The crystal structures reported in this study, and those of
      some related examples from the recent literature, show a wide variation in
      hydrogen-bonded aggregation consequent upon rather small changes in molecular
      constitution.

PMID- 18322343
TI  - N-methyl-N-phenylaminomethyl 2-naphthyl ketone: an X-ray diffraction and density
      functional theory study.
AB  - The crystallographically observed molecular structure of the title compound,
      C(19)H(17)NO, and its inverted counterpart are compared with that calculated by
      density functional theory (DFT) at the B3LYP/6-311++G(d,p) level. The results
      from both methods suggest that the observed molecular conformation of the title
      compound is primarily determined by intermolecular interactions in the crystal
      structure. The periodic organization of the molecules is stabilized by weak C
      H...O and C-H...pi hydrogen bonds and thus a two-dimensional puckered network
      consisting of R(4)(4)(22) and R(4)(4)(38) ring motifs is established. The title
      molecule has a (+)-antiperiplanar conformation about the C-C bond in the
      aminoacetone bridge. The pyramidal geometry observed around the vertex N atom is
      flattened by the presence of bulky phenyl and naphthylethanone fragments.

PMID- 18322344
TI  - Wave-like structure in 3-(4,6-diamino-1,3,5-triazin-2-yl)-2-naphthonitrile.
AB  - In the title compound, C(14)H(10)N(6), which crystallizes with Z' = 2 in the C2/c
      space group, the molecules are linked by N-H...N hydrogen bonds into chains,
      which are arranged in a wave-like form stabilized by aromatic pi-pi stacking
      interactions. This work demonstrates the usefulness of aromatic triazine
      derivatives in crystal engineering.

PMID- 18322345
TI  - Dispiro[indene-2,5'-indeno[2,1-a]fluorene-6',2''-indene]-1,1'',3,3'',11',12'
      hexaone: a three-dimensional hydrogen-bonded framework.
AB  - The title compound, C(36)H(16)O(6), (I), was obtained as a new and unexpected
      oxidation product of 1,2'-biindene-1',3,3'(2H)-trione. The molecules of (I)
      exhibit approximate, but noncrystallographic, twofold rotation symmetry and the
      central ring of the fused pentacyclic portion is distinctly puckered, with a
      conformation intermediate between half-chair and screw-boat. Six independent C
      H...O hydrogen bonds link the molecules into a three-dimensional framework
      structure of considerable complexity. Comparisons are drawn between the crystal
      structure of (I) and those of several simpler analogues, which show wide
      variation in their patterns of supramolecular aggregation.

PMID- 18322346
TI  - Bipodal 1,1'-acyl-3,3,3',3'-tetraalkylbis(thiourea) ligands with flexible C3, C4
      and C6 spacer groups.
AB  - In the structures of 3,3,3',3'-tetraethyl-1,1'-(propane-1,3
      diyldicarbonyl)bis(thiourea), C(15)H(28)N(4)O(2)S(2), (I), 3,3,3',3'-tetraethyl
      1,1'-(butane-1,4-diyldicarbonyl)bis(thiourea), C(16)H(30)N(4)O(2)S(2), (II), and
      3,3,3',3'-tetrabutyl-1,1'-(hexane-1,6-diyldicarbonyl)bis(thiourea),
      C(26)H(50)N(4)O(2)S(2), (III), compound (I) displays resonance-assisted hydrogen
      bonding, (II) exhibits an inversion centre, and both (II) and (III) are
      characterized by intermolecular hydrogen bonds between the carbonyl O atoms and
      thioamide H atoms, leading to chains of hydrogen-bonded molecules throughout the
      structures. The accurate structural data for these molecules is expected to
      assist in molecular modelling and other studies currently in progress.

PMID- 18322347
TI  - The monohydrates of the four polar dipeptides L-seryl-L-asparagine, L-seryl-L
      tyrosine, L-tryptophanyl-L-serine and L-tyrosyl-L-tryptophan.
AB  - The crystal structures of the four dipeptides L-seryl-L-asparagine monohydrate,
      C(7)H(13)N(3)O(5) x H(2)O, L-seryl-L-tyrosine monohydrate, C(12)H(16)N(2)O(5) x
      H(2)O, L-tryptophanyl-L-serine monohydrate, C(14)H(17)N(3)O(4) x H(2)O, and L
      tyrosyl-L-tryptophan monohydrate, C(20)H(21)N(3)O(4) x H(2)O, are dominated by
      extensive hydrogen-bonding networks that include cocrystallized solvent water
      molecules. Side-chain conformations are discussed on the basis of previous
      observations in dipeptides. These four dipeptide structures greatly expand our
      knowledge on dipeptides incorporating polar residues such as serine, asparagine,
      threonine, tyrosine and tryptophan.

PMID- 18322348
TI  - Borylated porphyrins: 5,10,15,20-tetrakis(5,5-dimethyl-1,3,2-dioxaborinan-2
      yl)porphyrin nitrobenzene disolvate.
AB  - The title compound, C(64)H(66)B(4)N(4)O(8) x 2 C(6)H(5)NO(2), is a nitrobenzene
      solvate of a meso-tetraphenylporphyrin species with unconventional peripheral
      boronic ester substituents. The porphyrin units reside in the crystal on centers
      of inversion and exhibit a channel clathrate-type structure, wherein molecules of
      nitrobenzene are accommodated in tunnels of width 7-8 A that propagate through
      the crystal parallel to the b axis between layers of tightly offset-stacked
      porphyrins. The scientific significance of the reported results is twofold. They
      describe the synthetic route to newly functionalized building blocks for the
      formulation of porphyrin-based supramolecular assemblies, namely the
      corresponding tetraboronic acid derivative; the title compound represents an
      essential intermediate in this process. They reveal also that channel-type
      clathrates can be formed not only with the parent tetraphenylporphyrins but also
      with their laterally extended derivatives.

PMID- 18322349
TI  - One-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds
      of 4,5-dichlorophthalic acid with 8-hydroxyquinoline, 8-aminoquinoline and
      quinoline-2-carboxylic acid (quinaldic acid).
AB  - The structures of the 1:1 proton-transfer compounds of 4,5-dichlorophthalic acid
      with 8-hydroxyquinoline, 8-aminoquinoline and quinoline-2-carboxylic acid
      (quinaldic acid), namely anhydrous 8-hydroxyquinolinium 2-carboxy-4,5
      dichlorobenzoate, C(9)H(8)NO(+) x C(8)H(3)Cl(2)O(4)(-), (I), 8-aminoquinolinium 2
      carboxy-4,5-dichlorobenzoate, C(9)H(9)N(2)(+) x C(8)H(3)Cl(2)O(4)(-), (II), and
      the adduct hydrate 2-carboxyquinolinium 2-carboxy-4,5-dichlorobenzoate
      quinolinium-2-carboxylate monohydrate, C(10)H(8)NO(2)(+) x C(8)H(3)Cl(2)O(4)(-) x
      C(10)H(7)NO(2) x H(2)O, (III), have been determined at 130 K. Compounds (I) and
      (II) are isomorphous and all three compounds have one-dimensional hydrogen-bonded
      chain structures, formed in (I) through O-H...O(carboxyl) extensions and in (II)
      through N(+)-H...O(carboxyl) extensions of cation-anion pairs. In (III), a
      hydrogen-bonded cyclic R(2)(2)(10) pseudo-dimer unit comprising a protonated
      quinaldic acid cation and a zwitterionic quinaldic acid adduct molecule is found
      and is propagated through carboxylic acid O-H...O(carboxyl) and water O
      H...O(carboxyl) interactions. In both (I) and (II), there are also cation-anion
      aromatic ring pi-pi associations. This work further illustrates the utility of
      both hydrogen phthalate anions and interactive-group-substituted quinoline
      cations in the formation of low-dimensional hydrogen-bonded structures.

PMID- 18322350
TI  - Ready reference to common segmental aneusomies by syndromic names, major features
      and chromosomal locations.
AB  - Abnormal gene dosage usually results in recognizable phenotypic abnormalities,
      especially if it involves a series of contiguous genes. Schmickel (1986) defined
      contiguous gene syndromes as diseases resulting from loss or gain of a series of
      adjacent genes. The terms microdeletion and microduplication as well as segmental
      aneusomy have also been used to describe such losses or gains that may not be
      readily detectable by Gbanded analysis. The loss (haploinsufficiency) or gain of
      a series of adjoining genes may result in a direct phenotypic effect and/or cause
      a genetic regulatory disturbance. Such syndromic gains or losses are often
      detectable when in situ hybridization of fluorescent labeled DNA probes or array
      comparative genomic hybridization technique are used (Gersen and Keagle 2005;
      Stumm et al. 1999; Barch, Knutsen and Spurbeck 1997). Segmental aneusomies
      generally occur due to homologous pairing between non-allelic low copy repeats
      (LCR) followed by crossing over. The LCRs, as part of the repetitive DNA
      sequences range from 1-500 Kb repeats, share >97% base sequence identity and
      constitute up to five percent of the genomic DNA. They are distributed throughout
      the genome, but are more concentrated near the centromeres and telomeres. A
      segment of 300 bp completely identical sequence within the LCRs is adequate for
      mediating non-allelic homologous or paralogous pairing. This process results in
      generating both deletion and duplication of a defined segment.

PMID- 18322351
TI  - Dr. R. J. McKinlay Gardner Interviewed by Dr. Hon Fong L. Mark.
AB  - Dr. Mac Gardner graduated in medicine from the University of Otago, Dunedin, New
      Zealand in 1968. After hospital residencies he undertook training in clinical
      genetics in New Zealand, and then the U.K., France and Canada. He returned to New
      Zealand as a specialist in genetics in 1977, but for the past 14 years he has
      been a consultant in medical genetics with Genetic Health Services Victoria in
      Melbourne, Australia.

PMID- 18322352
TI  - And the helix may set you free.
AB  - The first application of DNA forensics evidence was carried out by Dr. Alec
      Jefferies in 1983, in a British court case that sought to identify the
      relationship between an emigrant and her son. Since then, genotyping technology
      (also known as DNA fingerprinting and genetic profiling) has been developed and
      applied to identifying individuals for a wide variety of purposes including
      exonerating convicts. Faulty forensic evidence is a common cause of wrongful
      convictions. And once convicted, access to the forensic evidence remains a clear
      barrier to possible exoneration. In fact, it is DNA exoneration that is driving
      state legislators to address some of the apparent legislative flaws that govern
      forensic evidence testing in the U.S.

PMID- 18322353
TI  - Indian needs stricter implementation.....

PMID- 18322354
TI  - Point of sale tobacco advertisements in India.
AB  - BACKGROUND: The effect of any legislation depends on its implementation. Limited
      studies indicate that tobacco companies may tend to use such provision for
      surrogate advertising. The point of sale advertisement provision has been placed
      in the Indian Tobacco Control legislation. The study was undertaken to assess the
      Indian scenario in this regard. OBJECTIVE: To assess if there are any violations
      related to provision of point of tobacco sale advertisements under India's
      comprehensive tobacco Control legislation in different parts of India. MATERIALS
      AND METHODS: Boards over various shops showing advertisements of tobacco products
      were observed in the cities of Delhi, Mumbai, Kolkata, Trivandrum and Jaipur,
      between September 2005 and March 2006. RESULTS: The point of sale advertisements
      mushroomed after the implementation of 2004 tobacco control legislation. Tobacco
      advertisement boards fully satisfying the point of sale provision were
      practically non-existent. The most common violation of point of sale
      advertisements was the larger size of the board but with tobacco advertisement
      equal to the size indicated in the legislation and remaining area often showing a
      picture. Invariably two boards were placed together to provide the impression of
      a large single repetitive advertisement. More than two boards was not common.
      Tobacco advertisement boards were also observed on closed shops/ warehouses,
      shops not selling tobacco products and on several adjacent shops. CONCLUSION: The
      purpose of the point of sale advertisements seems to be surrogate advertisement
      of tobacco products, mainly cigarettes.

PMID- 18322355
TI  - Activity and toxicity of 2-CDA in Langerhans cell histiocytosis: a single
      institutional experience.
AB  - BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder characterized
      by clonal proliferation of immature and abnormal bone marrow derived langerhans
      cells. Treatment is usually multimodal. Potent anti-monocyte as well as
      immunomodulatory activity of 2-CDA and its proven efficacy in many
      lymphoproliferative disorders has made 2-CDA a rational choice in treatment of
      LCH. AIM: To evaluate the efficacy and toxicity profile of 2-CDA in children with
      relapsed or refractory LCH. SETTING AND DESIGN: This is a pilot study and we
      present the initial data of the first seven patients treated at our institution.
      MATERIALS AND METHODS: Seven patients of relapsed and refractory LCH were
      enrolled from July 2000 to June 2004. The cohort of seven patients included six
      males and one female with a median age at initiation of cladribine was 2.25 years
      (range, 1.67 to 7.0 years). Three patients had received one prior chemotherapy
      regimen while the rest were heavily pretreated. Cladribine was administered over
      two hours IV daily for five days and repeated every four weeks. RESULTS: After a
      median of six courses of cladribine (range, 2 to 9), two (33%) patients achieved
      PR and two (33%) patients have SD on imaging but are clinically better. None
      experienced grade 3 or 4 hematologic toxicity. At a median follow-up of 19 months
      (range, 8 to 52 months), five patients remain alive and one patient has died.
      CONCLUSION: Our study shows that single agent 2-CDA is active and well-tolerated
      in children with relapsed or refractory LCH.

PMID- 18322356
TI  - In vitro chemosensitivity profile of oral squamous cell cancer and its
      correlation with clinical response to chemotherapy.
AB  - CONTEXT: Oral cancers represent a disparate group of tumors with diverse clinical
      behavior and chemosensitivity profile. Currently, it is difficult to predict
      whether a tumor will respond to chemotherapy and which drug(s) will achieve the
      maximum clinical response. AIMS: To study in vitro chemosensitivity profile of
      oral cancers and to correlate the in vitro chemosensitivity of oral cancer to
      clinical response to chemotherapy. SETTINGS AND DESIGN: Prospective study in a
      tertiary cancer care center. METHODS AND MATERIAL: We prospectively studied the
      chemosensitivity profile of 57 untreated, advanced, unresectable oral cancers to
      cisplatin, methotrexate, 5-fluorouracil and their combinations by using
      histoculture drug response assay (HDRA) and correlated them to the clinical
      response to chemotherapy. STATISTICAL ANALYSIS USED: Chi Square test. RESULTS:
      Biopsy samples were successfully histocultured in 52/57 (91%) cases. Of these 52
      evaluable patients, 47 had primary gingivo-buccal cancers and five had tongue /
      floor of mouth cancers. Based on the assay, 27 (52%) tumors were sensitive to
      cisplatin, 27 (52%) to methotrexate, 24 (46%) to 5-fluorouracil, 38 (73%) to
      combination of cisplatin and methotrexate and 36 (69%) to combination of
      cisplatin and 5-fluorouracil. Of these, 31 patients with good performance status
      received two cycles of chemotherapy using one or more of these test drugs. There
      was a significant correlation (p=0.03) between the in vitro chemosensitivity and
      the clinical response. Negative predictive value of the test was 80%, positive
      predictive value-69%, sensitivity-79% and specificity -71%. The overall accuracy
      of the assay was 74%. CONCLUSIONS: We found HDRA to be a fairly good predictor of
      chemo-response of oral cancer.

PMID- 18322357
TI  - Validation of the University of Washington quality of life questionnaires for
      head and neck cancer patients in India.
AB  - Quality of life (QOL) is a multidimensional construct capturing the subjective
      wellbeing of patients in physical, emotional, functional and social domains.
      Available work on post treatment QOL have only been made in western literature
      and less in Indian literature. AIMS: To translate the UW-QOL into both Hindi and
      Marathi and psychometrically validate the translation in HandN cancer patients in
      Indian population. SETTINGS AND DESIGN: A prospective study was done at the Tata
      Memorial Hospital for patients who were treated for H and N cancers. MATERIALS
      AND METHODS: 147 patients were enrolled from January to April 2005. The study was
      carried out in two phases. Patients were given translated versions of the UW-QOL
      and EORTC QOL questionnaires pre-operatively, 15 days post-operatively and then
      three months post-operatively. RESULTS: Both the Hindi and Marathi translations
      had strong internal consistency (Cronbach's alpha=0.7971 and 0.7839). UW-QOL
      composite scores correlated well with the global questions on overall QOL in both
      the Hindi (r=0.69) and Marathi (r=0.66) translations and also with T-stage. QOL
      scores were worse three months post-operatively than pre-operatively and for
      patients undergoing surgery that violated the mucosa. A strong correlations was
      observed (r>0.50) between all similar domains on the UW-QOL and EORTC HandN35
      except the saliva item on the Marathi translation, where r< 0.50, but P-values
      were significant. CONCLUSIONS: The Marathi and Hindi versions of the UW-QOL
      appear to be valid and reliable instruments for assessing the QOL in Indian
      population and will be a vital tool for achieving greater insight into the short-
      and the long term QOL.

PMID- 18322358
TI  - Penile metastasis from rectal carcinoma.
AB  - Penile metastases are infrequent and often originate from genitor-urinary organs
      including bladder and prostate. In the present communication, we report an
      unusual case of penile metastasis from rectal adenocarcinoma. Though uncommon,
      this presentation is not unknown. A review of literature of penile metastases in
      colorectal cancers is also summarized here.

PMID- 18322359
TI  - Radiotherapy-induced depigmentation in a patient with breast cancer.
AB  - Vitiligo is a common dermatological disorder. A middle-aged woman with
      preexisting vitiligo was diagnosed with breast carcinoma. After surgery and
      chemotherapy she received regional radiotherapy. Six months after the completion
      of radiotherapy she developed depigmentation in the irradiated area. This article
      discusses the etiology for this phenomenon and the literature in this regard.

PMID- 18322360
TI  - Antibody response to influenza immunization in kidney transplant recipients
      receiving either azathioprine or mycophenolate: a controlled trial.
AB  - AIMS: We aimed to assess humoral immune response to the influenza vaccine in
      adult kidney transplant recipients (KTRs) subjected to two immunosuppressive
      regimens containing either mycophenolate mofetil (MMF) or azathioprine (Aza).
      METHODS: 40 eligible KTRs (24 treated with Aza [KTRs-Aza] and 16 treated with MMF
      [KTRs-MMF]) and 40 matched healthy controls (HCs) were administered the trivalent
      2006-2007 anti-influenza vaccine. Antibody (Ab) titers were measured before (pre
      vacc) and 1 month after (post-vacc) vaccination. The proportion of protective Ab
      titers (i.e. >or=1:40), the serological response (i.e. >or=4-fold rise in titers)
      rates, and the magnitudes of change in titers were evaluated. RESULTS: KTRs and
      HCs were similar in serologic responses, magnitudes of change in Ab titers, and
      proportions of acquired protective titers against all antigens. Whereas KTRs-MMF
      and KTRs-Aza were identical in magnitude of rise in titers as well as in
      serologic responses, KTRs-MMF did poorer in developing post-vacc-protective
      titers against A/H1N1 (p < 0.05). The function of the transplanted kidney has not
      deteriorated after vaccination. CONCLUSIONS: Anti-influenza vaccination was safe
      in KTRs and evoked Ab responses comparable to those of HCs. KTRs-MMF and KTRs-Aza
      responded almost equally to the vaccine. Annual anti-influenza vaccination can be
      recommended to all stable KTRs.

PMID- 18322361
TI  - Cognition in an ever-changing world: climatic variability is associated with
      brain size in Neotropical parrots.
AB  - Research on the conditions favoring the evolution of complex cognition and its
      underlying neural structures has increasingly stressed the role of environmental
      variability. These studies suggest that the ability to learn, behave flexibly and
      innovate would be favored under unpredictable variations in the availability of
      resources, as it would enable organisms to adjust to novel conditions. Despite
      the growing number of studies based on the idea that larger-brained organisms
      would be better prepared to cope with environmental challenges, direct testing of
      the association between brain size and environmental variability per se remains
      scant. Here we focus on Neotropical parrots as our model group and test the
      hypothesis that if relatively larger brains were favored in climatically variable
      environments, larger-brained species should currently tolerate a higher degree of
      environmental uncertainty. Although we show that there are also other factors
      underlying the dynamics of brain size variation in this group, our results
      support the hypothesis that proportionally larger-brained species are more
      tolerant to climatic variability, both on a temporal and spatial scale.
      Additionally, they suggest that the differences in relative brain size among
      Neotropical parrots represent multiple, recent events in the evolutionary history
      of the group, and are particularly tied to an increased dependence on more open
      and climatically unstable habitats. As this is the first study to present
      evidence of the link between brain size and climatic variability in birds, our
      findings provide a step towards understanding the potential benefits underlying
      variation in brain size and the maintenance of highly enlarged brains in this and
      other groups.

PMID- 18322362
TI  - Development of the olfactory system in a wallaby (Macropus eugenii).
AB  - We used carbocyanine dye tracing techniques in conjunction with hematoxylin and
      eosin staining, immunohistochemistry for GAP-43, and tritiated thymidine
      autoradiography to examine the development of the olfactory pathways in early
      pouch young tammar wallabies (Macropus eugenii). The overarching aim was to test
      the hypothesis that the olfactory system of newborn tammars is sufficiently
      mature at birth to contribute to the guidance of the pouch young to the nipple.
      Although GAP-43 immunoreactive fibers emerge from the olfactory epithelium and
      enter the olfactory bulb at birth, all other components of the olfactory pathway
      in newborn tammars are very immature at birth, postnatal day (P0). In particular,
      maturation of the vomeronasal organ and its projections to the accessory
      olfactory bulb appears to be delayed until P5 and the olfactory bulb is poorly
      differentiated until P12, with glomerular formation delayed until P25. The
      lateral olfactory tract is also very immature at birth with pioneer axons having
      penetrated only the most rostral portion of the piriform lobe. Interestingly,
      there were some early (P0) projections from the olfactory epithelium to the
      medial septal region and lamina terminalis (by the terminal nerve) and to
      olfactory tubercle and basal forebrain. The former of these is presumably serving
      the transfer of LHRH(+) neurons to the forebrain, as seen in eutherians, but
      neither of these very early pathways is sufficiently robust or connected to the
      more caudal neuraxis to play a role in nipple finding. Tritiated thymidine
      autoradiography confirmed that most piriform cortex pyramidal neurons are
      generated in the first week of life and are unlikely to be able to contribute to
      circuitry guiding the climb to the pouch. Our findings lead us to reject the
      hypothesis that olfactory projections contribute to guidance of the newborn
      tammar to the pouch and nipple. It appears far more likely that the trigeminal
      pathways play a significant role in this behavior because the central projections
      of the trigeminal nerve are more mature at birth in this marsupial.

PMID- 18322363
TI  - In vitro activities of various antibiotics, alone and in combination with
      colistin methanesulfonate, against Pseudomonas aeruginosa strains isolated from
      cystic fibrosis patients.
AB  - BACKGROUND: The in vitro activities of various antibiotics, either alone or in
      combination with colistin methanesulfonate, were assessed using Pseudomonas
      aeruginosa strains isolated from cystic fibrosis patients. METHODS: Except for
      colistin methanesulfonate, minimum inhibitory concentrations were determined by
      microbroth dilution technique as described by the Clinical and Laboratory
      Standards Institute (CLSI); for colistin methanesulfonate, a modified method of
      the CLSI was used. Minimum bactericidal concentrations were determined as
      described by the CLSI. The in vitro activities of antibiotics in combination were
      determined by microbroth checkerboard technique, and results were interpreted by
      fractional inhibitory concentration index. RESULTS: According to MIC values, 100,
      98, 96 and 84% of the isolates were found susceptible to amikacin, colistin
      methanesulfonate, meropenem and ceftazidime, respectively. The minimum
      bactericidal concentrations were generally equal to or twice as high as those of
      the minimum inhibitory concentrations. With a fractional inhibitory concentration
      index of < or =0.5 as borderline, synergistic interactions were more frequent
      with combinations where amikacin was involved than with those with colistin
      methanesulfonate. No antagonism was observed. CONCLUSION: The findings of this
      study may play a useful role in selecting the appropriate combinations when a
      single agent is inadequate to treat cystic fibrosis patients with P. aeruginosa
      infections.

PMID- 18322365
TI  - The 8th International Conference on Alzheimer's and Parkinson's Diseases.
      Preface.

PMID- 18322364
TI  - Effect of adenosine on membrane potential and Ca2+ in juxtaglomerular cells.
      Comparison with angiotensin II.
AB  - BACKGROUND: Renin is mainly secreted from the juxtaglomerular cells (JGC) in the
      kidney situated in the afferent arteriole close to the vessel pole. Angiotensin
      II (ANG II) and adenosine inhibit renin secretion and synergistically constrict
      the afferent arteriole. ANG II depolarises JGC and increases the cytoplasmic free
      Ca2+ concentration [Ca2+]i. The responses of JGC to adenosine are less known.
      METHODS: Effects of adenosine on membrane potential and [Ca2+]i were studied in
      afferent arterioles from NaCl-depleted rats and mice. RESULT: Stimulation of A1
      adenosine receptors (A1AR) by adenosine (10 microM) or cyclohexyladenosine (1
      microM) increased the spiking frequency of JGC, slightly depolarised the cells
      and, in < or =50% of the cases, increased [Ca2+]i. These effects were much
      smaller than those of ANG II (3 nM). Simultaneous application of
      cyclohexyladenosine and ANG II gave only additive effects on [Ca2+]i; in
      addition, responses to ANG II in JGC from A1AR knockout mice were similar to
      those from control mice. CONCLUSION: The small changes in membrane potential and
      [Ca2+]i in response to A1AR stimulation as compared to those of ANG II may
      suggest that these 2 tissue hormones use different signal transduction mechanisms
      to affect JGC function, including the inhibition of renin release.

PMID- 18322366
TI  - Basic research on dopamine in Parkinson's disease and the discovery of the
      nigrostriatal dopamine pathway: the view of an eyewitness.
AB  - The article recapitulates some of the historical facts that led up to the
      recognition of dopamine (DA) as a biologically active substance in the brain and
      its crucial role in Parkinson's disease (PD). Three events to which the writer
      has been an eyewitness are specially highlighted and placed in their proper
      historical perspective: (1) the discovery of the striatal DA deficit in the PD
      brain; (2) the development of the DA replacement treatment with L-dopa, and (3)
      the 'birth' of the nigrostriatal DA pathway. The opposition to the new
      observations and their unexpected and far-reaching consequences will be
      illustrated by briefly discussing the strongly negative opinions expressed by
      some famous brain scientists of the day about the relationship between the
      substantia nigra, PD, and the DA-containing nigrostriatal fiber connection.

PMID- 18322367
TI  - Neuropathological aspects of Alzheimer disease, Parkinson disease and
      frontotemporal dementia.
AB  - BACKGROUND: Proteinopathies are a heterogenous group of neurodegenerative
      disorders, characterized by intra- and extracellular accumulation of abnormal
      filament proteins. OBJECTIVE: To describe the neuropathology of specific forms of
      tauopathies and synucleinopathies, the overlap of morphologic features and
      molecular interactions. METHODS: The study uses currently available morphologic
      criteria of different proteinopathies. RESULTS: Alzheimer disease (AD) is
      featured by deposition of beta-amyloid peptides, phosphorylated tau protein (3-
      and 4-repeat tau) and frequent alpha-synuclein (aSyn) deposits. Lewy body
      diseases (LBD), such as sporadic Parkinson disease (PD) and dementia with Lewy
      bodies (DLB), show aSyn-positive deposits in neurons, neurites, glia, and
      presynaptic terminals, while frontotemporal dementias present tau-positive and
      tau-negative, ubiquitin- and TDP-43-positive neuronal and glial inclusions. The
      latter have also been observed in AD, PD, PD dementia and motor neuron disorders.
      Molecular interactions between major proteins, which may occur within the same
      brain in various distribution patterns, cause variable phenotypes and mixed
      pathologies, e.g. AD with aSyn pathology in the brainstem and amygdala, PD and
      DLB with AD lesions, and frontotemporal dementia with a mixture of various
      deposits, while others are featured by one principal pathology without other
      lesions (e.g. tangle-predominant type of dementia, pure PD, brainstem-predominant
      LBD). CONCLUSION: Animal models and in vitro studies showing co-occurrence and
      mutual promotion of fibrillation of these proteins indicate their synergistic
      interactions in the pathogenesis of these disorders which, at least in part, are
      genetically influenced.

PMID- 18322368
TI  - Etiology and pathophysiology of frontotemporal dementia, Parkinson disease and
      Alzheimer disease: lessons from genetic studies.
AB  - Genetic studies have led to major discoveries in the pathogenesis of various
      neurodegenerative diseases. Ubiquitin-positive familial frontotemporal dementia
      was recently found to be caused by mutations in the progranulin gene (PGRN), and
      the major constituent of the inclusions, TDP-43, was subsequently identified. The
      tau gene (MAPT) causes frontotemporal dementia with parkinsonism linked to
      chromosome 17. In Parkinson disease, LRRK2 mutations have emerged as a major
      cause of both familial and sporadic forms, adding to the previously known genes
      SNCA,PRKN,DJ1 and PINK1. Several genes have been implicated in Alzheimer disease,
      including the APP gene and the PSEN genes. Recently, variants in the sortilin
      related receptor 1 gene, SORL1, were associated with Alzheimer disease.

PMID- 18322369
TI  - Pathophysiology of neuronal energy crisis in Alzheimer's disease.
AB  - A large body of evidence indicates that sporadic Alzheimer's disease (AD) is a
      vascular disorder with neurodegenerative consequences and needs to be treated and
      managed as such. Epidemiologic studies of vascular risk factors, together with
      preclinical detection tools for AD are proof of concept that cerebral
      hypoperfusion is one of the earliest pathological signs in the development of
      cognitive failure. Vascular risk factors involving heart disease and stroke in
      the elderly individual who already possesses a dwindling cerebrovascular reserve
      due to advancing age contribute to further decline in cerebral blood flow (CBF)
      resulting in unrelenting brain hypoperfusion. Brain hypoperfusion, in turn, can
      reach a critically attained threshold of cerebral hypoperfusion (CATCH) giving
      rise to a neuronal energy crisis via reduced ATP synthesis. The ensuing metabolic
      energy crisis initially carves up ischemic-sensitive neurons in the hippocampus
      and posterior parietal cortex setting up cognitive meltdown and progressive
      neurodegenerative and atrophic changes in the brain. Neuronal energy compromise
      accelerates oxidative stress, excess production of reactive oxygen species,
      aberrant protein synthesis, ionic membrane pump dysfunction, signal transduction
      impairment, neurotransmitter failure, abnormal processing of amyloid precursor
      protein resulting in beta-amyloid deposition and axonal microtubule disruption
      from tau hyperphosphorylation. The high energy metabolic changes leading to
      oxidative stress and cellular hypometabolism precede clinical expression of AD.
      Regional CBF measurements using neuroimaging techniques can predict AD
      preclinically at the mild cognitive impairment stage or even before any clinical
      manifestation of dementia is expressed. Clinical diagnostic assessment of elderly
      persons who could develop or already present with memory complaints can prevent,
      reverse or slow down AD development. Although pathologic aging is the subject of
      thousands of studies, the question of why the elderly (and not younger people)
      succumb to AD has not been adequately addressed. The explanation(s) as to why
      vascular risk factors, for example, can trigger AD or vascular dementia usually
      in the elderly and not the young should provide vital clues in the search for a
      strategically effective dementia treatment. This review offers inductive
      hypothetical darts relative to that critical question.

PMID- 18322370
TI  - Biomarkers for the early detection of Parkinson's and Alzheimer's disease.
AB  - In the aging population of many countries in the world, neurodegenerative
      diseases like Parkinson's disease (PD) are becoming an increasing burden.
      Therefore, early therapy and ultimately disease prevention is essential, which is
      only possible with an early diagnosis. Besides a genetic predisposition, a number
      of biomarkers are being discussed to indicate vulnerability to PD, some of them
      many years before disease manifestation. These include hyperechogenicity of the
      substantia nigra as well as premotor symptoms like olfactory and autonomic
      dysfunction, depression, REM sleep behavior disorder, and neuropsychological
      impairment. Moreover, first signs of affection of the substantia nigra like PET
      and SPECT abnormalities and slight motor signs can be included, as they may be
      detected before a definite diagnosis according to motor symptoms can be made.
      Interestingly, other frequent neurodegenerative disorders like Alzheimer's
      disease (AD) are also characterized by a long preclinical period, with several
      biomarkers discussed as indicative for disease vulnerability including
      cerebrospinal fluid, serum, and neuroimaging biomarkers, olfactory dysfunction as
      well as subtle neuropsychological deficits. However, future studies are
      necessary, which establish the predictive value of these markers singularly and
      in combination to detect a subgroup of the population at risk for PD and AD not
      only to accelerate research on etiology and pathophysiology but also to promote
      testing for neuroprotective strategies.

PMID- 18322371
TI  - Early detection of Parkinson's disease: unmet needs.
AB  - A biomarker (biological marker) is a characteristic that is objectively measured
      and evaluated as an indicator of normal biological processes, pathogenetic
      processes or pharmacological responses to a therapeutic intervention.
      Expectations are high for the development of biomarkers since they make it
      possible to achieve a significant improvement in the diagnosis and classification
      of diseases like Parkinson's disease. As a surrogate marker for clinical studies,
      a biomarker can also be used to determine the efficacy of novel therapeutic
      interventions, such as neuroprotective strategies, and for monitoring the
      progress of the disease. Imaging techniques ((18)F-DOPA PET, (123)I-beta-CIT
      SPECT, MIBG scintigraphy, functional imaging), clinical tests (e.g. hyposmia,
      micrography, hyperechogenicity, apomorphine test), biochemical markers (e.g.
      alpha-synuclein and neuromelanin antibodies, oxidative and mitochondrial markers)
      and genetic tests for hereditary forms (PARK1 to PARK11) are evaluated for their
      suitability.

PMID- 18322372
TI  - Intraneuronal beta-amyloid is a major risk factor--novel evidence from the
      APP/PS1KI mouse model.
AB  - Accumulating evidence points to an important role of intraneuronal beta-amyloid
      (Abeta) in the development of Alzheimer's disease (AD), with its typical clinical
      symptoms like memory impairment and changes in personality. We have previously
      reported on the Abeta precursor protein and presenilin-1 knock-out (APP/PS1KI)
      mouse model with abundant intraneuronal Abeta(42) accumulation and a 50% loss of
      CA1 neurons at 10 months of age. In addition, we observed reduced short- and long
      term synaptic plasticity, hippocampal neuron loss, and reduced performance in a
      working memory task. These observations support a pivotal role of intraneuronal
      Abeta accumulation as a principal pathological trigger in AD.

PMID- 18322373
TI  - Physiologic origins of age-related beta-amyloid deposition.
AB  - BACKGROUND: Brain beta-amyloid (Abeta) deposition is an extremely common
      accompaniment of aging in humans and many other mammalian species. We
      hypothesized that normal physiological changes of aging cause Abeta deposition.
      OBJECTIVE: Three normal physiological aging changes were induced in young adult
      rabbits to determine their effects on brain Abeta concentrations and deposition.
      The three changes were cortical cholinergic deafferentation, hypercholesterolemia
      and estrogen deprivation. METHODS: Cortical cholinergic deafferentation was
      achieved through intracerebroventricular immunotoxin injection.
      Hypercholesterolemia was induced with a 2% cholesterol diet. Estrogen deprivation
      was modeled with ovariectomy. RESULTS: Cortical cholinergic deafferentation
      resulted in an 8-fold increase in cortical Abeta(42) concentrations and
      cerebrovascular Abeta deposition. Hypercholesterolemia increased cortical
      Abeta(42) 4.6-fold while ovariectomy increased cortical Abeta(42) 1.6-fold.
      CONCLUSION: At least three physiological changes of normal aging may underlie age
      related brain Abeta accumulation and Alzheimer's disease.

PMID- 18322374
TI  - Impact of intracellular beta-amyloid in transgenic animals and cell models.
AB  - The present commentary based on cell and animal models of intracellular beta
      amyloid (iAbeta) expression indicates that low levels of microscopically
      undetectable iAbeta could have a physiological role in the modulation of the
      cyclic AMP response element (CRE)-dependent gene expression and, as a
      consequence, a positive influence on synaptic plasticity (the 'good' Abeta?). On
      the other hand, high levels of iAbeta resembling the pathological and
      microscopically visible accumulation of this amyloid peptide, akin to that
      observed in Down syndrome and Alzheimer's disease, disrupt CRE-regulated gene
      expression, therefore compromising the protein synthesis-dependent component of
      long-term potentiation (the 'bad' Abeta?). Moreover, intracellular pathology
      would be independent and additive to the toxic effects of the extracellular Abeta
      burden.

PMID- 18322375
TI  - Beta-amyloid oligomers affect the structure and function of the postsynaptic
      region: role of the Wnt signaling pathway.
AB  - BACKGROUND: Alzheimer's disease (AD) is the most prevalent neurodegenerative
      disease in the growing population of elderly people. Synaptic dysfunction is an
      early manifestation of AD. The cellular mechanism by which beta-amyloid peptide
      (Abeta) affects synapses remains unclear. Abeta oligomers target synapses in
      cultured rat hippocampal neurons suggesting that they play a key role in the
      regulation of synapses. OBJECTIVE: The aim of this work is to study the effect of
      Abeta oligomers on the central synapses and the possible role of the Wnt
      signaling pathway in preventing the Abeta effects. METHODS: We used rat
      hippocampal neurons, immunofluorescence and western blot procedures to detect
      synaptic proteins. RESULTS: Abeta oligomers induced a reduction of the
      postsynaptic density protein 95 (PSD-95) and the NMDA glutamate receptors. We
      found that Wnt-5a, a noncanonical Wnt ligand, prevents the decrease triggered by
      Abeta oligomers in the glutamate receptor and PSD-95. CONCLUSION: Altogether, our
      results suggest that Abeta oligomers decrease the synaptic responses by affecting
      the postsynaptic region at different levels. The Wnt signaling activation
      prevents synaptic damage induced by Abeta, which raises the possibility of a new
      therapeutic intervention for the treatment of synaptic changes observed in AD.

PMID- 18322376
TI  - Potent beta-amyloid modulators.
AB  - Currently, the potential to interfere with the pathology of beta-amyloid
      targeting a well-known drugable enzyme, the acetylcholinesterase (AChE), is
      opened. Peripheral or dual binding site inhibitors of AChE may simultaneously
      alleviate the cognitive and behavioral deficits in Alzheimer's disease (AD)
      patients and, more importantly, act as disease-modifying agents delaying amyloid
      plaque formation. As part of a rational drug design program directed to find dual
      binding site AChE inhibitors, several families of compounds have been synthesized
      as potent AChE inhibitors. From these series, several drug candidates were
      selected based on their potent and selective inhibition of AChE (subnanomolar
      activity) and their interference with the beta-amyloid aggregation in vitro
      (IC(50) in the low micromolar range). First in vivo data confirm our initial
      hypothesis. Oral treatment with NP-61 for 3 months is able to reverse the
      cognitive impairment (Morris water maze test) and to reduce plaque load in the
      brains of human amyloid precursor protein transgenic mice (Swedish mutation).
      These results suggest that NP-61, a potent beta-amyloid modulator, is able to
      reverse the AD-like neurodegenerative phenotype in transgenic mice, indicating a
      promising disease-modifying agent for clinical application.

PMID- 18322377
TI  - Soluble beta-amyloid leads to mitochondrial defects in amyloid precursor protein
      and tau transgenic mice.
AB  - BACKGROUND: Mitochondrial dysfunction has been identified in neurodegenerative
      disorders including Alzheimer's disease, where accumulation of beta-amyloid
      (Abeta) and oxidative stress seem to play central roles in the pathogenesis, by
      probably directly leading to mitochondrial dysfunction. OBJECTIVE: In order to
      study the in vivo effect of Abeta load during aging, we evaluated the
      mitochondrial function of brain cells from transgenic mice bearing either mutant
      amyloid precursor protein (tgAPP) or mutant amyloid precursor protein and mutant
      PS1 (tgAPP/PS1) as well as from nontransgenic wild-type littermates. tgAPP mice
      exhibit onset of Abeta plaques at an age of 6 months, but the intracellular
      soluble Abeta load is already increased at 3 months of age. In contrast, onset of
      Abeta plaques starts at an age of 3 months in tgAPP/PS1 mice. In addition, we
      investigated the effects of different Abeta preparations on mitochondrial
      function of brain cells from tau transgenic mice. RESULTS: Of note, mitochondrial
      damage such as reduced mitochondrial membrane potential and ATP levels can
      already be detected in the brains from these mice before the onset of plaques. In
      agreement with our findings in tgAPP mice, soluble Abeta induced mitochondrial
      dysfunction in brain cells from tau transgenic mice. CONCLUSION: Our results
      indicate that mitochondrial dysfunction is exacerbated by the presence of soluble
      Abeta species as a very early event during pathogenesis.

PMID- 18322378
TI  - Processes of beta-amyloid and intracellular cytoplasmic domain generation by
      presenilin/gamma-secretase.
AB  - BACKGROUND/AIMS: Following extracellular shedding, transmembrane domains (TMs) of
      beta-amyloid precursor protein (betaAPP) and Notch-1 undergo proteolysis by
      presenilin (PS)/gamma-secretase at least at two sites, near the middle of the TM
      (gamma-/S4 cleavage) and at the interface between cytosol and the TM (epsilon-/S3
      cleavage), releasing Alzheimer disease (AD)-associated beta-amyloid (Abeta)/Notch
      1beta (Nbeta) and betaAPP intracellular cytoplasmic domain (AICD)/Notch-1
      intracellular cytoplasmic domain (NICD). Inhibiting PS/gamma-secretase activity
      is an essential approach to AD treatment, but it also decreases NICD production,
      which may cause severe side effects. Therefore, it is important to investigate
      the differences between the cleavages at the two sites. Gamma-/S4 and epsilon
      cleavages have diversity, and produce a number of Abeta/Nbeta and AICD species.
      S3 cleavage diversity has been recently identified. It is significant that each
      cleavage occurs with strict precision, not randomly. METHODS: Biochemical
      analysis of cultured cells was performed to explore the processing mechanisms.
      RESULTS: Familial AD-associated PS1 mutations as well as a subset of nonsteroidal
      anti-inflammatory drugs cause similar changes in gamma-/S4 cleavage precision,
      suggesting a common process for these cleavages near the middle of the TM. While
      the precision of the epsilon-cleavage is drastically affected by physiological
      factors, that of epsilon-/S3 cleavage is not. CONCLUSION: The processes of the
      two cleavages occurring in different portions of TMs may be diverse, thus
      representing possible targets for anti-AD therapeutics to selectively reduce
      Abeta.

PMID- 18322379
TI  - Distinct functional effects of human 5-HT4 receptor isoforms on beta-amyloid
      secretion.
AB  - BACKGROUND: The serotonin 5-HT(4) receptor is of potential interest for the
      treatment of Alzheimer's disease because it increases memory and learning and
      influences amyloid precursor protein (APP) processing. Several 5-HT(4) receptor
      isoforms have been cloned in humans. They all belong to the G-protein-coupled
      receptor superfamily and differ in composition and length of their amino acid
      intracellular C-terminal sequence. At present, it is still unknown whether 5
      HT(4) receptor isoforms may have distinct effects on APP processing. OBJECTIVE:
      In this study, we investigated the effect of an ultrashort isoform of the human 5
      HT(4) receptor (2 amino acids after the splicing site), the 5-HT(4(d)) receptor
      isoform (h5-HT(4(d))), on APP processing in Chinese hamster ovary cells (CHO
      cells). METHODS: Non-amyloidogenic soluble sAPPalpha was determined by immunoblot
      and beta-amyloid peptides (Abeta(1-40) and Abeta(1-42)) were assayed by ELISA in
      CHO cells stably expressing h5-HT(4(d)) and transiently transfected with human
      APP(695). RESULTS: We show here that activation of h5-HT(4(d)) strongly
      stimulates the release of sAPPalpha and concomitantly decreases extracellular
      Abeta peptides. These data contrast with our previous findings showing that the
      h5-HT(4(e/g)) receptor isoform, which has 20 amino acids after the splicing site,
      did not influence Abeta secretion. CONCLUSION: We conclude that C-terminal tails
      of 5-HT(4) receptor isoforms may influence their functional effect on Abeta
      secretion and that the pathways regulating either beta- or gamma-secretase may be
      differentially controlled by 5-HT(4) receptor isoforms.

PMID- 18322380
TI  - Activation of the amyloid cascade by intracerebroventricular injection of the
      protease inhibitor phosphoramidon.
AB  - We presently investigated the pathological effects of prolonged inhibition of
      brain beta-amyloid (Abeta) degradation in vivo. The results obtained revealed
      that intracerebroventricular injection of the protease inhibitor phosphoramidon
      into wild-type mice for up to a month elevated the soluble and deposited brain
      Abeta levels and concomitantly induced the neurodegeneration of distinct
      hippocampal neurons as well as neuroinflammation. These findings reproduce
      pathological effects associated with the initial stages of the amyloid cascade
      and provide a novel model system for studying their underlying mechanisms.

PMID- 18322381
TI  - Mechanism of glial differentiation of neural progenitor cells by amyloid
      precursor protein.
AB  - BACKGROUND: We found that human neural progenitor cells (HNPCs) exposed to high
      concentrations of amyloid precursor protein (APP) or transplanted into APP
      transgenic mice (APP23) primarily differentiated into astrocytes, suggesting that
      pathological alterations of APP processing in Alzheimer's disease (AD) may
      prevent neuronal differentiation of HNPCs. OBJECTIVES: To investigate the
      mechanism of APP-induced glial differentiation of HNPCs. METHODS: We treat HNPCs
      with APP and analyze the expression and phosphorylation of signaling molecules
      using PCR and Western blots. To confirm the involvement of the factors, RNA
      interference of the signaling molecule is conducted. RESULTS: APP treatment
      caused inductions of CNTF, gp130 and JAK1 gene expressions, and STAT3
      phosphorylation, while silencing of these genes by RNA interference suppressed
      the glial differentiation of the cells, indicating involvement of the IL-6/gp130
      pathway. APP also increased the generation of notch intracellular domain and gene
      expression of Hes1, indicating that glial differentiation of HNPCs may be
      mediated by the notch signaling. CONCLUSION: These results indicate that APP may
      regulate HNPC differentiation through activation of both the IL-6/gp130 and notch
      signaling pathway. Although the importance of adult neurogenesis is not clear,
      glial differentiation of HNPCs may cause problems in maintaining normal brain
      function and may contribute to the AD pathology.

PMID- 18322382
TI  - Preamyloid lesions and cerebrovascular deposits in the mechanism of dementia:
      lessons from non-beta-amyloid cerebral amyloidosis.
AB  - The importance of amyloid plaques in the pathogenesis of dementia is usually
      centered on beta-amyloid (Abeta) and its role in Alzheimer's disease (AD).
      However, since fibrillar plaques correlate poorly with neurodegeneration,
      challenging their importance in the mechanism(s) of dementia, investigators
      turned their focus to the importance of soluble oligomers and the role of
      preamyloid and cerebrovascular deposits. Two non-Abeta cerebral amyloidoses,
      familial British and Danish dementias (FBD and FDD), share many aspects of AD,
      including cognitive impairment and the presence of neurofibrillary tangles in
      limbic areas. The lack of compact plaques in FDD and in many areas in FBD further
      questions the importance of these lesions in the mechanism of dementia. The main
      components of the deposits--ABri and ADan--are structurally unrelated to Abeta
      and yet they all have a high tendency to oligomerize and assemble into amyloid
      fibrils in vitro and form ion-like channels in lipid membranes. Thus, different
      amyloid species have the capability to induce similar neuropathological changes,
      which are neither exclusive for Abeta nor dependent on the presence of compact
      plaques. These findings reaffirm the notion that non-Abeta amyloidoses constitute
      alternative models to study the role of preassembled amyloid subunits in neuronal
      death.

PMID- 18322383
TI  - Influence of pharmacogenetic factors on Alzheimer's disease therapeutics.
AB  - Alzheimer's disease (AD) is the result of the phenotypic expression of more than
      200 genes which are potentially involved in neurodegeneration. Structural and
      functional genomics studies demonstrate that genomic factors, probably induced by
      environmental factors, cerebrovascular dysfunction, and epigenetic phenomena,
      might be responsible for AD pathogenesis leading to premature neuronal death.
      Drug metabolism, pharmacokinetics and pharmacodynamics are genetically regulated
      complex traits in which hundreds of genes may participate. Pharmacogenetics
      studies show that the therapeutic response in AD is genotype specific, with APOE
      4/4 carriers as the worst responders to conventional treatments. In addition,
      about 10-20% of Caucasians are carriers of defective CYP2D6 polymorphic variants
      that alter the metabolism and effects of AD drugs and many psychotropic agents
      currently administered to patients with dementia. With multifactorial therapies,
      combining different drugs, it is possible to slow down cognitive deterioration in
      parallel with improvement in noncognitive symptoms; however, the association of
      the APOE-4 allele with specific genetic variants of other genes negatively
      modulates the therapeutic response to multifactorial treatments affecting
      cognition, mood and behavior. Pharmacogenetic factors may account for 60-90% of
      drug variability in drug disposition and pharmacodynamics. The incorporation of
      pharmacogenetic protocols into AD research and clinical practice can foster
      therapeutics optimization by improving drug efficacy and safety.

PMID- 18322384
TI  - Functional genomics dissects pathomechanisms in tauopathies: mitosis failure and
      unfolded protein response.
AB  - BACKGROUND: Alzheimer's disease (AD) is characterized by beta-amyloid (Abeta)
      peptide-containing plaques and tau-containing neurofibrillary tangles. By
      intracerebral injection of Abeta(42), both pathologies have been combined in
      P301L tau mutant mice. Furthermore, in cell culture, Abeta(42) induces tau
      aggregation. While both Abeta(42) and mutant tau cause neuronal dysfunction,
      their modes of action are only vaguely understood. METHODS: To determine which
      processes are disrupted by Abeta(42) and/or P301L mutant tau, we used
      transcriptomic and proteomic techniques followed by functional validation and
      analysis of human AD tissue. RESULTS: Our transcriptomic study in the SH-SY5Y
      cell culture system revealed that Abeta(42) and P301L tau expression
      independently affect genes controlling the cell cycle and cell proliferation.
      Proteomics applied to Abeta(42)-treated P301L tau-expressing SH-SY5Y cells and
      the amygdala of Abeta(42)-injected P301L transgenic mice revealed that a
      significant fraction of proteins altered in both systems belonged to the same
      functional categories, i.e. stress response and metabolism. Among the proteins
      identified was valosin-containing protein (VCP), a component of the quality
      control system during endoplasmic reticulum stress. Mutations in VCP have
      recently been linked to frontotemporal dementia. CONCLUSION: Our data support the
      mitosis failure hypothesis that claims that aberrant cell cycle reentry of
      postmitotic neurons induces apoptosis. Furthermore, our data underline a role of
      Abeta(42) in the stress response associated with protein folding.

PMID- 18322385
TI  - Investigating convergent actions of genes linked to familial Parkinson's disease.
AB  - BACKGROUND: Mutations in LRRK2 are among the most frequent genetic changes
      identified in Parkinson's disease (PD), but how LRRK2 contributes to the
      pathophysiology of PD is not known. OBJECTIVES: To investigate how expressing
      wild-type or G2019S LRRK2 modifies cellular responses to rotenone, a
      mitochondrial toxin. METHODS: We investigated the vulnerability to mitochondrial
      toxins in Caenorhabditis elegans expressing wild-type or G2019S LRRK2. RESULTS:
      We observed a powerful role for LRRK2 in mitochondrial biology. Overexpressing
      LRRK2 strongly protects C. elegans against rotenone toxicity. The G2019S LRRK2
      construct also protected LRRK2 against rotenone, but to a lesser degree than wild
      type LRRK2. Knockdown of lrk-1 potentiated rotenone toxicity. CONCLUSIONS: These
      data suggest that LRRK1/2 regulate mitochondrial physiology.

PMID- 18322386
TI  - Apolipoprotein E epsilon 4 allele is associated with increased atrophy in
      progressive mild cognitive impairment: a voxel-based morphometric study.
AB  - BACKGROUND: The apolipoprotein E (APOE) epsilon4 allele is a risk factor for
      Alzheimer's disease. Earlier studies have shown differences in brain structure
      according to the APOE epsilon4 status. OBJECTIVE: To assess possible differences
      in brain structure according to the APOE epsilon4 status in mild cognitive
      impairment (MCI) subjects in relation to conversion to dementia. METHODS: In a
      follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI)
      during a mean follow-up time of 31 months. Brain structure differences in both
      stable MCI (SMCI) and PMCI epsilon4 carriers and noncarriers in the baseline MRI
      scan were assessed with voxel-based morphometry. RESULTS: The SMCI epsilon4
      carriers had atrophy in the amygdala and hippocampus compared to the SMCI
      noncarriers. The PMCI epsilon4 carriers revealed atrophy of the left inferior
      frontal gyrus and parietal cortex compared to the PMCI noncarriers. CONCLUSION:
      The rate of brain atrophy in certain brain areas may be increased in epsilon4
      positive MCI subjects progressing to dementia.

PMID- 18322387
TI  - Neuroinflammation in plaque and vascular beta-amyloid disorders: clinical and
      therapeutic implications.
AB  - BACKGROUND: The cerebral beta-amyloid (Abeta) disorders show a great variability
      in the distribution of parenchymal and vascular amyloid deposits. OBJECTIVE: To
      study the relationship between amyloid deposition and inflammatory responses in
      three distinct subtypes of cerebral Abeta disorders. METHODS: The distribution of
      inflammatory proteins and cells in vascular and plaque amyloid deposits was
      evaluated in postmortem brain tissue using immunohistochemistry. The effects of a
      mixture of Abeta peptides and inflammation-related Abeta-associated proteins were
      studied in postmortem obtained human microglia cell cultures. RESULTS: The
      chronic inflammatory response is associated with amyloid plaques (but not with
      amyloid in the walls of larger vessels) in Alzheimer's disease (AD), with amyloid
      in cerebral arteries in hereditary cerebral hemorrhage with amyloidosis-Dutch
      type and with amyloid microangiopathy in the vascular variant of AD. Abeta(1-42)
      fibrils complexed with complement factor C1q and serum amyloid P component (the
      relevant amyloid-associated proteins) stimulate the production of proinflammatory
      cytokines in human microglia cell cultures and this production is attenuated by
      minocycline. CONCLUSION: The pattern of the chronic inflammatory response
      associated with fibrillar Abeta is strikingly different in the three studied
      types of Abeta disorders. The site of the fibrillar Abeta-induced chronic
      inflammatory response is closely related to clinical symptoms. Minocycline is a
      drug of interest to inhibit microglia-mediated neuroinflammatory response in
      Abeta brain disorders.

PMID- 18322388
TI  - Progress in the active immunotherapeutic approach to Alzheimer's disease:
      clinical investigations into AN1792-associated meningoencephalitis.
AB  - BACKGROUND: In a phase 2a clinical trial of AN1792 (Study 201), a potential
      immunotherapeutic agent for use in Alzheimer's disease (AD), approximately 6% of
      the treated AD patients (18/300) developed meningoencephalitis (ME). OBJECTIVE:
      To elucidate potential immune mechanisms of treatment-induced ME. METHODS:
      Peripheral blood mononuclear cells obtained from patients who received AN1792
      were stimulated in vitro either with beta-amyloid (Abeta) or various overlapping
      peptides of Abeta(1-42), followed by quantification of cytokine-secreting cells
      by enzyme-linked immunosorbent spot assay. RESULTS: A significant difference in
      the quality of the T-cell responses between patients in Study 201 and those in
      earlier studies of AN1792 was noted. T-cell responses specific to the carboxy
      terminus of Abeta elicited from patients' peripheral blood mononuclear cells in
      an earlier multiple dose study (Study 102) were Th2 biased, while those from
      Study 201 were biased toward a proinflammatory Th1 response. Antibody responses
      in both studies were quantitatively and qualitatively similar (as determined by
      epitope mapping). The addition of polysorbate 80 to the formulation used in Study
      201 is the most likely explanation for the difference in the T-cell response.
      CONCLUSION: ME following injection of AN1792 may be related to immune response
      differences driven by a formulation change. To address this, a novel peptide
      carrier protein conjugate using an amino-terminal fragment of Abeta (ACC-001) has
      been developed to avoid potentially harmful T-cell responses, while maintaining a
      similar antibody response to that of AN1792. Immunotherapeutic trials using this
      treatment approach in AD patients are in progress.

PMID- 18322389
TI  - Engineered heparins: novel beta-secretase inhibitors as potential Alzheimer's
      disease therapeutics.
AB  - BACKGROUND: Cleavage of beta-amyloid precursor protein (APP) by the protease beta
      secretase (BACE1) is a key step in beta-amyloid peptide processing. We have
      described a novel role for heparan sulphate polysaccharides in Alzheimer's
      disease pathology as naturally occurring inhibitors of beta-secretase, suggesting
      new avenues for discovery of novel drugs for Alzheimer's disease based on
      heparins. OBJECTIVE: To evaluate engineered heparin analogues as novel beta
      secretase inhibitors in vitro, including modifications to increase
      bioavailability. METHODS: We tested a number of selectively desulphated and
      chemically modified heparins for their ability to inhibit BACE1 and other
      proteases in vitro using APP fluorescent resonance energy transfer peptide
      substrates RESULTS: Several lead compounds have been identified that are
      effective beta-secretase inhibitors, but have negligible activity as
      anticoagulants or as inhibitors of other aspartyl proteases structurally related
      to beta-secretase. In addition, the compounds studied also give some insight into
      the structural interaction between beta-secretase and heparin, indicating that
      the structure of the polysaccharide is much more important than charge.
      CONCLUSION: We have demonstrated that modifications to increase bioavailability
      of chemically modified heparins have little effect on their efficacy as beta
      secretase inhibitors. Therefore, these heparins show promise for development as a
      novel class of pharmaceuticals that target the underlying pathology of
      Alzheimer's disease. We have also found further evidence that it is the structure
      of the polysaccharide that is important for the interaction with beta-secretase,
      not simply the level of sulphation or charge.

PMID- 18322390
TI  - Neuroprotective properties of glycosaminoglycans: potential treatment for
      neurodegenerative disorders.
AB  - Previous studies suggest that proteoglycans and glycosaminoglycans (GAGs) may
      play an important role in the pathogenesis and/or alleviation of
      neurodegenerative disorders, including Alzheimer's disease (AD). Proteoglycans
      increase the formation of neurofibrillary tangles, and stimulate the aggregation
      of beta-amyloid (Abeta). This effect, on the other hand, is believed to be
      competitively inhibited by certain GAGs. Over the past few years, we have
      examined the neuroprotective properties of Neuroparin (C3), a low-molecular
      weight GAG (approx. 2.1 kDa), in animal models of lesions characteristic of AD.
      Neuroparin is composed of 4-10 oligosaccharides, and it is derived from heparin
      involving depolymerization of heparin by gamma irradiation. In our experiments,
      Neuroparin protected against cholinergic lesions induced by
      intracerebroventricular injection of a specific cholinotoxin, AF64A, in rats.
      Administration of Neuroparin attenuated AF64A-stimulated, low-affinity nerve
      growth factor receptor-immunoreactive axonal varicosities in the rat septum, and
      increased arborization of hippocampal CA1 neurons. Neuroparin also reduced the
      septal caspase 3 immunoreactivity induced by AF64A treatment. Moreover,
      Neuroparin reduced tau 2 immunoreactivity in the rat hippocampus, stimulated by
      intra-amygdaloid injection of Abeta(25-35). These findings are in good agreement
      with our previous data indicating a neuroprotective role of GAGs. These results,
      plus others, all suggest that Neuroparin may possess neuroprotective properties
      against many of the characteristic neural lesions in AD. Since our
      pharmacokinetic studies revealed that Neuroparin is capable of crossing the blood
      brain barrier, Neuroparin may, conceivably, open an entirely new avenue in the
      treatment of neurodegenerative disorders. Phase I studies have been completed,
      and have proven to be extremely supportive in that regard.

PMID- 18322391
TI  - Regulation of proBACE1 by glycosaminoglycans.
AB  - The beta-secretase (BACE1) is initially synthesized as a partially active zymogen
      containing a prodomain which can be further activated through proteolytic
      cleavage of the prodomain by a furin-like protease. The active site of BACE1 is
      large and although a number of high-affinity active-site inhibitors of BACE1 have
      been described, most of these compounds are large, polar and do not cross the
      blood-brain barrier. However, it may be possible to target other regions of the
      protein which regulate BACE1 allosterically. We have found that proBACE1 can be
      stimulated by relatively low concentrations (e.g. 1 microg/ml) of heparin.
      Heparin initially increases proBACE1 activity, probably by binding to the
      prodomain, which decreases steric inhibition at the active site. However, the
      heparin-activated zymogen also undergoes autocatalysis, which ultimately leads to
      a loss of enzyme activity. We speculate that proBACE1 can be regulated by
      endogenous heparan sulfate proteoglycans and that drugs which target this
      interaction may have value in the treatment of Alzheimer's disease.

PMID- 18322392
TI  - Conformationally altered p53: a putative peripheral marker for Alzheimer's
      disease.
AB  - The identification of biological markers of Alzheimer's disease (AD) can be
      extremely useful to improve diagnostic accuracy and/or to monitor the efficacy of
      putative therapies. In this regard, peripheral cells may be of great importance
      because of their easy accessibility. After subjects were grouped according to
      diagnosis, the expression of conformational mutant p53 in blood cells was
      compared by immunoprecipitation or by a cytofluorimetric assay. One hundred and
      four patients with AD, 92 age-matched controls, 15 patients with Parkinson's
      disease, and 9 with other types of dementia were analyzed. Two independent
      methods to evaluate the differential expression of a conformational mutant p53
      were developed. Mononuclear cells were analyzed by immunoprecipitation or by flow
      cytometric analysis, following incubation with a conformation-specific p53
      antibody, which discriminates unfolded p53 tertiary structure. Mononuclear cells
      from AD patients express a statistically significantly higher amount of mutant
      like p53 compared to mononuclear cells from non-AD subjects, thus supporting the
      study of conformational mutant p53 as a new putative marker to discriminate AD
      from non-AD patients. We also observed a strong positive correlation between the
      expression of p53 and the age of patients. The expression of mutant p53 did not
      correlate with the duration of illness and the Mini Mental State Examination
      scores.

PMID- 18322393
TI  - ACAT as a drug target for Alzheimer's disease.
AB  - Accumulation of beta-amyloid peptide (Abeta) in the brain regions responsible for
      memory and cognitive functions is a neuropathological hallmark of Alzheimer's
      disease. Cholesterol may be involved in many aspects of Abeta metabolism. It
      affects generation, aggregation and clearance of Abeta in the brain. Not only the
      amount but also the distribution of cholesterol within cells appears to modulate
      Abeta biogenesis. ACAT is an enzyme that regulates subcellular cholesterol
      distribution by converting membrane cholesterol to cholesteryl esters for storage
      and transport. We have used various cell- and animal based models to show that
      inhibition of ACAT strongly reduces Abeta generation and protects from amyloid
      pathology. Here, we discuss data supporting ACAT inhibition as a strategy to
      treat Alzheimer's disease.

PMID- 18322394
TI  - In vivo and postmortem clinicoanatomical correlations in frontotemporal dementia
      and parkinsonism linked to chromosome 17.
AB  - BACKGROUND: Frontotemporal dementia and parkinsonism linked to chromosome 17
      (FTDP-17) is associated with mutations in the Microtubule-Associated Protein
      Tau(MAPT) gene or the Progranulin(PGRN) gene. MAPT mutations lead to widespread
      deposition of hyperphosphorylated tau protein (FTDP-17T). PGRN mutations are
      associated with ubiquitin- and TDP-43-positive inclusions in the frontotemporal
      cortex, striatum and hippocampus (FTDP-17U). Despite the differences, FTDP-17T
      and FTDP-17U share a largely overlapping clinical phenotype. OBJECTIVE: To
      determine whether neuroimaging studies may allow an in vivo early differentiation
      between FTDP-17T and FTDP-17U. METHODS: We studied 25 individuals affected with
      FTDP-17T associated with either the exon 10+3 (24 subjects) or the G335S (1
      subject) MAPT mutation, as well as 3 FTDP-17U individuals, who were carriers of
      the A9D, IVS6-2A>G or R493X PGRN mutation. Neuroimaging studies, obtained along
      the course of the disease, were compared to the neuropathologic findings.
      RESULTS: FTDP-17T cases were associated with symmetric frontotemporal atrophy.
      Behavioral changes constituted the predominant clinical presentation. Conversely,
      an asymmetric degenerative process was seen in all 3 PGRN cases, who presented
      with either corticobasal syndrome (A9D) or frontotemporal dementia and language
      deterioration (IVS6-2A>G and R493X). CONCLUSION: Neuroimaging data, in the early
      disease stage of FTDP-17, may offer the possibility of an early differentiation
      of FTDP-17T and FTDP-17U phenotypes, independent of the genetic analysis.

PMID- 18322395
TI  - The role of alpha-synuclein in neurodegenerative diseases: a potential target for
      new treatment strategies?
AB  - Alpha-synuclein (AS) is the main constituent of Lewy bodies. There is an ongoing
      discussion if overexpression is already dangerous, or if toxicity is subjected to
      oligomers, protofibrils or mature aggregates. The facts that the central
      hydrophobic part of AS is also a constituent of amyloid plaques in Alzheimer's
      disease (AD) and that a majority of patients have Lewy bodies and Lewy neurites
      in specific brain areas raised our interest in the contribution of AS to AD
      pathogenesis. The N-terminal amino acid sequence 1-15 of beta-synuclein (BS)
      seems to be a natural antiaggregation factor for AS. We synthesized a library
      with different sequence variations. Several of these peptides displayed
      neuroprotective activity in tissue culture models of neurodegeneration induced by
      oxidative stress or beta-amyloid 1-42. In spite of the fact that these peptides
      have a short half-life, a significant in vivo reduction in brain plaque load and
      improvement of behavior was demonstrated in amyloid precursor protein transgenic
      mice after intranasal treatment for 2 months. KEGV, the shortest sequence, was
      also active after intraperitoneal application. The in vitro effects cannot be
      explained by the antiaggregatory potential, but most likely by interaction of BS
      derivates with antiapoptotic PI3/Akt or antioxidative pathways. The possibility
      that BS-derived peptidomimetics act as neuroprotectants and prevent protein
      misfolding suggests therapeutic usefulness.

PMID- 18322396
TI  - Leucine-rich repeat kinase 2 colocalizes with alpha-synuclein in Parkinson's
      disease, but not tau-containing deposits in tauopathies.
AB  - BACKGROUND: Mutations in leucine-rich repeat kinase 2 (LRRK2) are thus far the
      most frequent genetic cause associated with autosomal dominant and idiopathic
      Parkinson's disease. OBJECTIVE: To examine whether LRRK2 is directly associated
      with the pathological structures of Parkinson's disease, dementia with Lewy
      bodies, and other related disorders using highly specific antibodies to LRRK2.
      RESULTS: LRRK2 antibodies strongly labeled brainstem and cortical Lewy bodies,
      the pathological hallmarks of Parkinson's disease and dementia with Lewy bodies,
      respectively. We found that 20-100% (mean 60%) of alpha-synuclein-positive Lewy
      bodies contained LRRK2. While antibodies raised against various regions of LRRK2
      were previously shown to label recombinant LRRK2 on Western blots, only
      antibodies raised against the N- and C-termini, but not the regions containing
      folded protein domains of LRRK2, immunolabeled Lewy bodies. In Alzheimer's
      disease, Hirano bodies were found to contain LRRK2 and the neurofibrillary
      tangles in progressive supranuclear palsy remained unlabeled. CONCLUSIONS:
      Information on the cellular localization of LRRK2 under normal and pathological
      conditions will deepen our understanding of its functions and molecular pathways
      relevant to the progression of Parkinson's disease and related disorders.

PMID- 18322397
TI  - Polymorphisms at the paraoxonase 1 L55M and Q192R loci affect the pathophysiology
      of Alzheimer's disease: emphasis on the cholinergic system and beta-amyloid
      levels.
AB  - BACKGROUND: Paraoxonase 1 (PON1) functions to protect the cholinergic system
      against nerve gases and the organophosphate family of pesticides. Recent studies
      have shown that polymorphisms at the PON1 L55M and Q192R loci might affect
      individual susceptibility to experience-derived and environmental events such as
      the exposure to inhibitors of cholinesterase (ChEIs). OBJECTIVE: ChEI therapy
      being the treatment of choice for mild-to-moderate Alzheimer's disease (AD)
      patients, we determined whether genetic variations in the PON1 loci are
      associated with AD risk and whether they affect brain choline acetyltransferase
      (CHAT) activity, nicotinic receptor density, and beta-amyloid (Abeta) levels in
      different regions of AD and age-matched control subjects. METHODS: This pilot
      genetic study used a small cohort of brains from autopsy-confirmed AD patients
      and age-matched controls from the Douglas Hospital Brain Bank, Quebec, Canada.
      RESULTS: The frequency of the M55M genotype at the PON1 L55M locus was found to
      be significantly increased in AD patients relative to age-matched controls (p <
      0.05). Significant associations were observed between the PON1 L55M and Q192R
      polymorphisms and frontal cortex Abeta levels as well as CHAT activity and
      nicotinic receptor density in the temporal cortex. CONCLUSIONS: Our results
      suggest a prominent role for PON1 in the pathophysiology of common AD with a
      marked impact on the cholinergic system and Abeta levels in the brain.

PMID- 18322398
TI  - Galanin hyperinnervation upregulates choline acetyltransferase expression in
      cholinergic basal forebrain neurons in Alzheimer's disease.
AB  - BACKGROUND: Fibers containing galanin (GAL) enlarge and hyperinnervate
      cholinergic basal forebrain (CBF) nucleus basalis (NB) neurons in late-stage
      Alzheimer's disease (AD), yet the physiological consequences of this phenomenon
      are unclear. OBJECTIVE: To determine whether GAL hyperinnervation of cholinergic
      NB neurons modulates the expression of genes critical to cholinergic transmission
      [e.g. acetylcholine (ACh) metabolism and ACh receptors] in AD. METHODS: Single
      cell gene expression profiling was used to compare cholinergic mRNA levels in non
      GAL-hyperinnervated NB neurons in tissue autopsied from cases classified as
      having no cognitive impairment (NCI) or late-stage AD (AD/GAL-) and in GAL
      hyperinnervated (AD/GAL+) NB neurons from the same AD subjects. RESULTS: AD/GAL+
      cells displayed a significant upregulation in choline acetyltransferase (ChAT)
      mRNA expression compared to NCI and AD/GAL- cells. CONCLUSION: GAL fiber
      hyperinnervation of cholinergic NB neurons upregulates the expression of ChAT,
      the synthetic enzyme for ACh, suggesting that GAL regulates the cholinergic tone
      of CBF neurons in AD.

PMID- 18322399
TI  - Human recombinant butyrylcholinesterase purified from the milk of transgenic
      goats interacts with beta-amyloid fibrils and suppresses their formation in
      vitro.
AB  - BACKGROUND: In Alzheimer's disease (AD), brain butyrylcholinesterase (BChE) co
      localizes with beta-amyloid (Abeta) fibrils. AIMS: In vitro testing of the
      significance of this phenomenon to AD progress. METHODS: A thioflavine T (ThT)
      fluorogenic assay, photo-induced cross-linking and quantifiable electron
      microscopy served to compare the effect on Abeta fibril formation induced by
      highly purified recombinant human BChE (rBChE) produced in the milk of transgenic
      goats with that of serum-derived human BChE. RESULTS: Both proteins at 1:50 and
      1:25 ratios to Abeta dose-dependently prolonged the ThT lag time and reduced the
      apparent rate of Abeta fibril formation compared to Abeta alone. Photo-induced
      cross-linking tests showed that rBChE prolonged the persistence of amyloid
      dimers, trimers and tetramers in solution, whereas Abeta alone facilitated
      precipitation of such multimers from solution. Transmission electron microscopy
      showed that rBChE at 1:100 to Abeta prevented the formation of larger, over 150
      nm-long, Abeta fibrils and reduced fibril branching compared to Abeta alone as
      quantified by macro programming of Image Pro Plus software. CONCLUSION: Our
      findings demonstrate that rBChE interacts with Abeta fibrils and can attenuate
      their formation, extension and branching, suggesting further tests of rBChE, with
      unlimited supply and no associated health risks, as a therapeutic agent for
      delaying the formation of amyloid toxic oligomers in AD patients.

PMID- 18322400
TI  - M1 muscarinic agonists target major hallmarks of Alzheimer's disease--the pivotal
      role of brain M1 receptors.
AB  - The M1 muscarinic receptor (M1 mAChR) is a therapeutic target in Alzheimer's
      disease (AD) and the M1-selective muscarinic agonists AF102B, AF150(S) and AF267B
      are cognitive enhancers and potential disease modifiers. Notably, AF267B
      decreased cerebrospinal fluid beta-amyloid (Abeta(40) and Abeta(42)) in rabbits,
      decreased brain Abeta levels in hypercholesterolemic rabbits and vascular
      Abeta(42) deposition from the cortex in cholinotoxin-treated rabbits. In triple
      transgenic AD mice, AF267B reduced cognitive deficits and decreased Abeta(42) and
      tau pathologies in the cortex and hippocampus (not amygdala), via M1 mAChR
      activation of protein kinase C and a disintegrin and metalloproteinase domain 17
      (ADAM17 or TACE) and decreased beta-site amyloid precursor protein-cleaving
      enzyme 1 and glycogen synthase kinase 3beta, respectively. AF267B is the first
      reported low-molecular-weight therapy that targets the major AD hallmarks.

PMID- 18322401
TI  - Glutamatergic approaches to the treatment of cognitive and behavioural symptoms
      of Alzheimer's disease.
AB  - The glutamatergic system has long been recognised for its role in learning and
      memory and recent studies indicate an early loss of glutamatergic synapses in
      Alzheimer's disease (AD). Efforts to produce drugs which address changes in the
      glutamatergic system in AD are well advanced (e.g. memantine and drugs in
      development such as ampakines). Much less is known about the possible role of
      glutamate in non-cognitive behavioural changes; however, recent data from
      clinical trials suggest that memantine reduces agitation and aggressive behaviour
      in AD patients. In this context, it is important to help identify new treatment
      approaches to replace the use of antipsychotics in this vulnerable population.

PMID- 18322402
TI  - Duodenal levodopa infusion improves quality of life in advanced Parkinson's
      disease.
AB  - BACKGROUND: A significant percentage of patients with Parkinson's disease (PD)
      continue to experience motor fluctuations and dyskinesias despite the association
      of dopamine agonists and levodopa with COMT or MAO-B inhibitors. The use of
      apomorphine infusion is limited by compliance while deep brain stimulation is
      feasible only for a small number of patients mostly because of age constraints.
      OBJECTIVE: To assess prospectively the effectiveness of duodenal levodopa
      infusion on quality of life as well as motor features in patients with advanced
      PD. In all but 1 case levodopa infusion was stopped at nighttime. METHODS: We
      report the outcome of 22 PD patients, followed for up to 2 years, who were on
      continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic
      gastrostomy. RESULTS: We found a significant reduction in 'off' period duration
      as well as dyskinesia severity (Unified Parkinson's Disease Rating Scale part IV,
      items 33 and 39). There was significant improvement in the 39-item Parkinson's
      Disease Quality of Life Questionnaire as well as in the Unified Parkinson's
      Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew:
      2 for poor compliance and 3 for adverse events (1 was related to percutaneous
      endoscopic gastrostomy). CONCLUSIONS: These results demonstrate significant
      clinical improvements in quality of life and activities of daily living
      consistent with the occurrence of a satisfactory therapeutic response and a
      reduction in dyskinesia severity.

PMID- 18322403
TI  - Lithium, a potential protective drug in Alzheimer's disease.
AB  - Alzheimer's disease is characterized by the presence of two histopathological
      aberrant structures, the senile plaques and the neurofibrillary tangles. The main
      component of these tangles is the cytoskeletal protein tau in hyperphosphorylated
      form. Since a main tau kinase is glycogen synthase kinase 3 (GSK-3), the use of
      specific GSK-3 inhibitors, like lithium, could be a potential therapy in
      Alzheimer's disease. In this short article, we have done a review on tau
      phosphorylation in Alzheimer's disease and other tauopathies, and on the
      inhibition of kinases like GSK-3, involved in tau modification.

PMID- 18322405
TI  - Effects of aging on neuroprotective and neurotoxic properties of microglia in
      neurodegenerative diseases.
AB  - The inflammatory process in the brain, which is accompanied by changes in the
      levels of proinflammatory cytokines and neurotrophins, along with the presence of
      activated microglia, has recently gained much attention in neurodegenerative
      diseases. Activated microglia produce either neuroprotective or neurotoxic
      factors. Many reports indicate that activated microglia promote degeneration of
      dopamine (DA) neurons in Parkinson's disease (PD). On the other hand, there are
      several lines of evidence that microglia also have a neuroprotective function.
      Microglia activated with lipopolysaccharide in the nigrostriatum of neonatal mice
      protect DA neurons against the PD-producing neurotoxin 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine (MPTP), whereas activated microglia in aged mice promote DA
      cell death by MPTP. These results suggest that the function of activated
      microglia may change in vivo from neuroprotective to neurotoxic during aging as
      neurodegeneration progresses in the PD brain.

PMID- 18322404
TI  - Seeding neuritic plaques from the distance: a possible role for brainstem neurons
      in the development of Alzheimer's disease pathology.
AB  - BACKGROUND AND OBJECTIVE: Our goal is to obtain insight into the causes of the
      pathological lesions in Alzheimer's disease (AD). It is thought that the beta
      amyloid (Abeta) deposits within the cerebral cortex and hippocampus of AD brains
      are initiated by a 'bad seed' of oligomeric Abeta. The origin of this seed is
      unknown. Here, we focused on the events that might trigger the formation of
      neuritic plaques, aiming to explain how these plaques form in cortical and
      hippocampal regions. METHODS AND RESULTS: Using immunocytochemical and
      biochemical methods, we showed that brainstem-derived, neuronal cells (CAD)--but
      not cortical or hippocampal neurons--show large amounts of Abeta accumulated at
      the terminals of their processes. This is similar to what is believed to occur in
      brain neurons, in the early phases of AD. CAD cells that contain Abeta
      accumulations also concentrate beta-secretase at process terminals. We show that,
      while the anterograde transport of small vesicles is not significantly affected,
      the mitochondrial transport is perturbed in CAD cells that contain Abeta
      accumulations. We further show that intracellular, neuritic Abeta accumulations
      may become extracellular upon neurite degeneration, thus providing the initial
      'bad seed' of Abeta oligomers that triggers further aggregation of extracellular
      proteins. CONCLUSION: We propose that brainstem neurons, known to send
      projections throughout the brain, could provide the 'bad seed' of Abeta that
      nucleates plaques in the cerebral cortex and hippocampus of AD brains.

PMID- 18322406
TI  - The long-term effects of oophorectomy on cognitive and motor aging are age
      dependent.
AB  - BACKGROUND: The evidence for a neuroprotective effect of estrogen in women
      remains controversial. OBJECTIVE: We studied the long-term risk of parkinsonism
      and of cognitive impairment or dementia in women who underwent oophorectomy
      before menopause. METHODS: We conducted a historical cohort study among all women
      residing in Olmsted County, Minn., USA, who underwent unilateral or bilateral
      oophorectomy before the onset of menopause for a noncancer indication from 1950
      through 1987. Each member of the oophorectomy cohort was matched by age to a
      referent woman from the same population who had not undergone oophorectomy. In
      total, we studied 1,252 women with unilateral oophorectomy, 1,075 women with
      bilateral oophorectomy, and 2,368 referent women. Women were followed for a
      median of 25-30 years. Parkinsonism was assessed using screening and examination,
      through a medical records-linkage system, and through death certificates.
      Cognitive status was assessed using a structured questionnaire via a direct or
      proxy telephone interview. RESULTS: The risk of parkinsonism and of cognitive
      impairment or dementia increased following oophorectomy. In particular, we
      observed significant linear trends of increasing risk for either outcome with
      younger age at oophorectomy. CONCLUSION: Our findings, combined with previous
      laboratory and epidemiologic findings, suggest that estrogen may have an age
      dependent neuroprotective effect.

PMID- 18322407
TI  - Assessing change in cognitive function in dementia: the relative utilities of the
      Alzheimer's Disease Assessment Scale-Cognitive Subscale and the Cognitive Drug
      Research system.
AB  - This paper considers the suitability of the Alzheimer's Disease Assessment Scale
      Cognitive Subscale (ADAS-cog) as the gold standard in registration trials of
      treatments for Alzheimer's disease. Working groups have recommended replacing the
      ADAS-cog if suitable automated alternatives can be found. This paper makes the
      case for the Cognitive Drug Research (CDR) computerised cognitive assessment
      system, as an example of a suitable instrument to replace the ADAS-cog. The CDR
      system has been widely used in dementia work for 20 years and shows good
      correlations to the ADAS-cog, while additionally assessing the domains of
      attention, working memory, information processing and retrieval speed of
      information held in memory. The utility of the system in evaluating and
      differentiating the major dementias will be described, as well as its ability to
      track deterioration over time. Its validation as a core measure of cognitive
      dysfunction in the dementias will be described, as will work showing that various
      CDR measures relate closely to activities of daily living. The sensitivity of the
      CDR system to anticholinesterases will be described in Alzheimer's disease,
      dementia with Lewy bodies and Parkinson's dementia. Finally, the CDR system has a
      large normative database which allows treatment effects in dementia to be put
      into an unambiguous clinical perspective.

PMID- 18322408
TI  - Can we afford the war on cancer?

PMID- 18322409
TI  - Gene therapy in mesotheliomas.

PMID- 18322410
TI  - Oncological resource allocation in Germany.
AB  - BACKGROUND: Oncology is a resource-intensive medical discipline where, so far,
      effectiveness rather than efficiency of a treatment has stood in the foreground.
      The aim of our study was, therefore, to determine the resource allocation and to
      assess the efficiency of oncology in Germany for the period of 2002-2004.
      MATERIALS AND METHODS: With the aid of the official German Health Report, the
      expenditures for health in 2004 and the gain in years of life according to ICD 10
      disease categories were analyzed. Based on the incremental costs and years of
      life gained, the cost calculation per year of life gained was made. RESULTS:
      Malignant neoplasms appear in 5th place in health expenditures at a cost of 15
      billion 1. With costs per year of life gained of 140,750 1, malignant neoplasms
      range ahead of respiratory diseases (52,500 1)digestive diseases (27,455 1), and
      injuries (14,538 1). Costs involving malignant neoplasm per year of life gained
      range between 39,000 1(malignancies of the lip, oral cavity, and the pharynx),
      and 126,000 1(digestive organ cancer). CONCLUSION: In Germany, oncology incurs
      higher costs per year of life gained as compared to several other diseases. Also,
      in malignant neoplasm considerable differences can be observed regarding resource
      allocation and efficiency.

PMID- 18322411
TI  - Characterization of human mesothelioma cell lines as tumor models for suicide
      gene therapy.
AB  - BACKGROUND: The median survival time of patients with malignant pleural
      mesothelioma (MPM) remains poor. Therefore, novel therapeutic options are in high
      demand, and well characterized model systems for in vitro/vivo screening have to
      be established. MATERIAL AND METHODS: For this purpose, 3 MPM cell lines (H-Meso
      1, MSTO211H, and NCI-H28) were characterized and tested for susceptibility to
      recombinant adeno-associated virus 2 (rAAV2)-based vectors which have the
      potential for a loco-regional application. RESULTS: Using multiplex fluorescence
      in situ hybridization, several recurrent chromosomal aberrations were observed
      for each of the MPM cell lines. Tumorigenicity of H-Meso-1 and MSTO-211H cells
      was shown in an intraperitoneal NOD/SCID mouse model, whereas NCI-H28 cells did
      not yield any tumors. Although all 3 cell lines were readily susceptible to rAAV2
      vectors, differences in susceptibility were observed (H-Meso-1 > NCI-H28 > MSTO
      211H). Furthermore, the efficacy of a potential suicide gene therapy using an
      rAAV2 suicide vector-transduced MPM cell line was determined in a proof-of
      feasibility in vivo experiment. CONCLUSION: The characterized cell lines
      described here may serve as a model for in vitro and in vivo preclinical gene
      therapy for the treatment of MPM using rAAV2 suicide vectors.

PMID- 18322412
TI  - Postoperative sense of well-being and quality of life in breast cancer patients
      do not depend on type of primary surgery.
AB  - BACKGROUND: In primary breast cancer, breast conserving surgery and mastectomy
      are equal options with regard to patient survival. We therefore investigated
      whether and how the type of surgery has impact on the patients' quality of life
      (QoL) in order to support individualized surgical concepts in treatment of breast
      cancer. 3 types of surgery are compared: breast-conserving surgery; modified
      radical mastectomy with or without primary reconstruction. PATIENTS AND METHODS:
      91 out of 114 consecutive patients diagnosed with histologically confirmed
      primary breast cancer agreed to answer the QoL questionnaires within the first 2
      years of their follow-up care. 2 recognized questionnaires on sense of well-being
      and QoL were used: Multidimensional Mood Questionnaire and QoL SF-12. RESULTS: No
      significant correlation between sense of well-being and type of operation or
      tumor stage was found. With regard to health-related QoL, we saw no significant
      correlation with type of surgery. However, low tumor stage was significantly
      correlated with better physical (p = 0.012) but not psychological well-being.
      CONCLUSION: Within the first 2 years after primary surgery for breast cancer, we
      did not find significant differences in sense of well-being or QoL dependent on
      type of surgery.

PMID- 18322413
TI  - Early prediction of therapy outcome in patients with high-risk soft tissue
      sarcoma using positron emission tomography.
AB  - BACKGROUND: 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: The ongoing evaluation includes 27 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 2 cycles of EIA chemotherapy, respectively. Restaging
      according to RECIST was performed after 6 cycles of AI-G or 4 cycles of EIA
      chemotherapy and served as reference. RESULTS: Clinical outcome of 27 evaluable
      patients was as follows: 2 patients with no evidence of disease, 7 with partial
      remission, 14 with stable disease, and 4 patients with progressive disease. A
      significant difference of the progression-free survival for patients with a
      decrease in the standardised uptake value (SUV; responders) in comparison to
      patients with an increase or stable SUV (non-responders) could be demonstrated (p
      = 0.0187). CONCLUSION: On the basis of these data, prediction of chemo
      sensitivity of the tumour and moreover of the therapy outcome might be possible.

PMID- 18322414
TI  - Isolated bone marrow natural killer cell lymphoma with central nervous system
      involvement mimicking a cerebral infarct.
AB  - BACKGROUND: We describe the case of an isolated bone marrow natural killer (NK)
      cell lymphoma with central nervous system (CNS) involvement mimicking a cerebral
      infarct. CNS involvement in isolated bone marrow lymphoma has not been reported
      previously. CASE REPORT: A 49-year-old man with complaints of fever, confusion,
      and agitation was presented. A bone marrow biopsy was performed to investigate
      the etiology of bicytopenia which was consistent with NK-cell lymphoma. Brain MRI
      findings were suggestive of a subacute infarct. CONCLUSION: Even if pathological
      signal changes of the brain without contrast enhancement resembling infarct are
      detected in patients with lymphoma on the magnetic resonance imaging, CNS
      involvement of the lymphoma should be kept in mind in the differential diagnosis.

PMID- 18322415
TI  - Complete response of CNS-involved olfactory neuroendocrine tumor using multimodal
      therapy.
AB  - INTRODUCTION: Locally advanced tumors in the olfactory area commonly have central
      nervous system (CNS) involvement and are often incurable. CASE REPORT: We report
      the treatment of a 25-year-old male patient who presented with a large,
      neuroendocrine tumor arising from the ethmoid complex. This locally invasive
      lesion extended beyond the orbits and into the anterior cranial fossa with
      associated intracranial involvement. An endoscopic nasal biopsy demonstrated a
      poorly differentiated neuroendocrine tumor. The patient was treated with 4 cycles
      of combination induction chemotherapy with irinotecan and cisplatin followed by
      radiation therapy with concurrent weekly cisplatin. He had a complete response to
      this therapy confirmed with biopsies that demonstrated no residual disease at 8
      weeks after chemoradiotherapy. He remained disease free one and a half years
      following surgery. CONCLUSION: To our knowledge, this combination treatment
      approach has not been reported in the literature.

PMID- 18322416
TI  - Erlotinib in patients with previously irradiated, recurrent brain metastases from
      non-small cell lung cancer: two case reports.
AB  - BACKGROUND: With the current improvements in primary lung care, the long-term
      control of brain metastases becomes a clinical challenge. No established
      therapeutic approaches exist for cranial relapse after response to previous
      radiotherapy and systemic therapy. Tyrosine kinase inhibitors like erlotinib with
      its proven activity in non-small cell lung cancer may provide clinical benefits
      in such patients. PATIENTS AND METHODS: Two case reports are presented
      illustrating the efficacy of erlotinib in patients with recurrent brain
      metastases and parallel thoracic progression. RESULTS: Both patients showed
      lasting partial remissions in the brain and lung, and clinical symptom
      improvement. CONCLUSION: The observed survival times of above 18 and 15 months,
      respectively, since occurrence of cranial disease manifestation in line with the
      achieved progression-free survival times of 9 and 6 months by the erlotinib third
      line therapy are remarkable. The use of targeted therapies after wholebrain
      irradiation should be investigated more systematically in prospective clinical
      trials.

PMID- 18322417
TI  - Venous thromboembolism and pancreatic cancer: incidence, pathogenesis and
      clinical implications.
AB  - Pancreatic cancer is still a major clinical challenge. Recent efforts to improve
      survival in locally advanced and metastatic disease have focused on combining
      cytotoxic drugs with targeted therapies. One of the major complications of
      pancreatic cancer is venous thromboembolism (VTE). Despite the general perception
      that patients with mucinous carcinoma of the pancreas and gastrointestinal tract
      present a high incidence of thromboembolic complications, there is little data
      regarding the incidence and pathogenesis of VTE in pancreatic cancer patients.
      Clinical data suggest that, among patients with unresectable pancreatic cancer,
      the occurrence of VTE may be associated with reduced overall survival.
      Furthermore emerging clinical data strongly suggest that anticoagulant treatments
      may improve cancer patient survival by decreasing thromboembolic complications as
      well as by anticancer effects. Given the lack of extensive data and the clinical
      relevance of this topic for both physicians and basic research scientists, this
      overview focuses attention on the incidence, pathogenesis and clinical
      implications of VTE in pancreatic cancer patients.

PMID- 18322418
TI  - Breast ductal endoscopy: do not neglect education.

PMID- 18322419
TI  - Paclitaxel induces vascular endothelial growth factor expression through reactive
      oxygen species production.
AB  - The antineoplastic drug paclitaxel is known to block cells in the G2/M phase of
      the cell cycle through stabilization of microtubules. The development of
      paclitaxel resistance in tumors is one of the most significant obstacles to
      successful therapy. Vascular endothelial growth factor (VEGF) and hypoxia
      inducible factor 1 (HIF-1) are important regulators of neovascularization. HIF-1
      regulates VEGF expression at the transcriptional level. Here, we investigated
      whether paclitaxel treatment affects VEGF expression for the development of
      paclitaxel resistance. Paclitaxel treatment induced dose-dependent cell death and
      increased VEGF expression. Paclitaxel also induced nuclear factor-kappaB
      activation and stabilized HIF-1alpha, which stimulated luciferase activity of HIF
      1alpha response element on VEGF gene. As paclitaxel treatment produced reactive
      oxygen species (ROS), VEGF expression was increased by H2O2 treatment and reduced
      by various ROS scavengers such as N-acetyl-L-cysteine, pyrrolidine
      dithiocarbamate and diphenylene iodonium. Paclitaxel-induced cell death was
      aggravated by incubation with those ROS scavengers. Collectively, this suggests
      that paclitaxel-induced VEGF expression could be mediated by paclitaxel-induced
      ROS production through nuclear factor-kappaB activation and HIF-1alpha
      stabilization, which could affect resistance induction to antitumor therapeutics
      during cancer treatment.

PMID- 18322421
TI  - Nasal valve suspension revisited.
AB  - OBJECTIVES: Nasal valve suspension (NVS) is a simple technique to correct nasal
      valve obstruction or collapse by providing a lateral vector of pull on the nasal
      sidewall. The purpose of this research was to review our experience with NVS in a
      cohort of patients with nasal valve collapse, including a subset of patients with
      facial paralysis. The objectives were to determine patient satisfaction and
      complication rates after NVS. STUDY DESIGN: A retrospective review of patients 18
      years and older who had NVS from 2003 to 2006 with a follow-up of at least 1
      month was performed. METHODS: Data were collected on diagnosis, surgical
      outcomes, complications, and treatments required. Complications included adverse
      outcomes, infections, and the need for repeat surgery or treatments. RESULTS: In
      17 charts reviewed, 9 patients (53%) had nasal valve collapse as a result of
      facial paralysis, and 8 (47%) had previous nasal surgery. Follow-up ranged from 1
      to 30 months, with a mean of 16.5. Moderate to complete resolution of obstruction
      was reported by 82% of patients, or for 88% of procedures. Sustained relief was
      observed in two of eight patients who had previous nasal surgery and six of nine
      who had no previous nasal surgery (P = .1). Infection occurred in four (24%)
      patients and five (21%) total suspensions and ranged from 1.5 to 7 months. Six
      (35%) patients experienced a loss of suspension at 6 to 22 months. CONCLUSIONS:
      NVS is a technically straightforward, relatively reversible procedure
      particularly useful in the patient with facial paralysis. The efficacy is
      excellent in the short term yet appears to diminish with time.

PMID- 18322422
TI  - AM-111 reduces hearing loss in a guinea pig model of acute labyrinthitis.
AB  - OBJECTIVES/HYPOTHESIS: This study investigated the otoprotective properties of AM
      111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation.
      STUDY DESIGN: A controlled, prospective animal study using a guinea pig model of
      acute labyrinthitis. METHODS: Acute labyrinthitis was generated by injection of
      antigen into the scala tympani of sensitized guinea pigs. Treatment groups
      received 100 microL of AM-111 at concentrations of 100 micromol/L, 10 micromol/L,
      and 1 micromol/L in a hyaluronic acid gel formulation delivered over the round
      window niche within 1 hour of antigen challenge. Cochlear function was monitored
      over 21 days with serial auditory brainstem response (ABR) and distortion product
      otoacoustic emission (DPOAE) measurements followed by histologic analysis.
      RESULTS: The ABR results on day 21 demonstrated that untreated control ears for
      acute labyrinthitis had a mean hearing loss (HL) of 68 +/- 12 dB. In contrast,
      ears treated with AM-111 (100 micromol/L) had a mean HL of 39 +/- 31 dB. These
      two groups were statistically different (one-way analysis of variance, P = .03).
      Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory
      cell counts, and spiral ganglion density, were also statistically significant in
      favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce
      a statistically significant reduction in HL over controls. CONCLUSION: AM-111
      delivered over the round window membrane in a 100 microL hyaluronic acid
      formulation at a 100 micromol/L concentration immediately after induction of
      acute labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell
      loss, and reduces the number of inflammatory cells at 21 days after treatment.

PMID- 18322423
TI  - Ototoxicity of topical moxifloxacin in a chinchilla animal model.
AB  - OBJECTIVE: Ciprofloxacin is currently the only proven nonototoxic topical
      antibiotic. However, its widespread use has resulted in the emergence of
      antimicrobial resistance. There are also concerns that there is currently no safe
      alternative to ciprofloxacin for patients with a nonintact eardrum. We thus
      wished to evaluate whether a moxifloxacin solution is ototoxic when used
      topically in chinchilla ears in the presence of a pressure-equalizing tube (PET).
      STUDY DESIGN: A prospective, randomized, controlled trial was conducted in an
      animal model. METHODS: Twenty chinchillas were included in this study. After
      bilateral insertion of PETs, four drops of a moxifloxacin solution were delivered
      twice daily for 7 days in the randomly assigned experimental ear. The control ear
      received an equal amount of a solution of Ringer's lactate. Distortion product
      otoacoustic emissions (DPOAE) were recorded at baseline (after PET insertion) and
      at days 1, 3, 7, 14, and 28 after treatment initiation. RESULTS: When baseline
      DPOAE measurements were compared with the final measurements at day 28,
      moxifloxacin caused a statistically significant (P < .05) hearing loss (HL) in
      the experimental ears for the frequencies between 3.7 and 15 kHz. There was no
      significant change in hearing in the control ears. CONCLUSION: This represents
      the first study on the ototoxicity of topical moxifloxacin. Our results
      demonstrate that moxifloxacin causes HL when used with a nonintact tympanic
      membrane in a chinchilla animal model.

PMID- 18322424
TI  - Imaging of the pediatric airway using optical coherence tomography.
AB  - OBJECTIVES: Optical coherence tomography (OCT) is an imaging modality that uses a
      broadband light source to produce high-resolution cross-sectional images in
      living tissue (8-20 microm). A prospective study of normal, benign, and
      pathologic tissues in the pediatric airway was conducted to assess the utility of
      OCT technology in characterizing the microanatomy of the pediatric upper
      aerodigestive tract in vivo. STUDY DESIGN: Prospective clinical trial. MATERIALS
      AND METHODS: Fifteen patients from 1 to 17 years of age underwent surgical
      endoscopy and OCT for various airway disorders. OCT imaging was performed at a
      frame rate of 1 Hz using a 1.3-microm broadband light source to produce images
      1.6 x 6 mm in vertical and horizontal dimensions. The epithelium, lamina propria,
      and unique tissue microstructures were visualized and then measured using digital
      micrometry. Direct comparison of OCT images with endoscopic photography was
      performed. RESULTS: Systematic imaging of the oral cavity, oropharynx,
      hypopharynx, and larynx was performed in all 15 patients. Normal microstructures
      identified included papillae, ducts, glands, and vessels, whereas pathologic
      conditions included distinct zones of mature scar, granulation tissue, edema,
      ulceration, and papillomatosis. Endoscopic photographs were well correlated with
      OCT images. CONCLUSIONS: OCT is capable of obtaining high-resolution microanatomy
      images of pediatric airway in vivo tissue. OCT clearly identifies the epithelium
      and lamina propria while providing detailed structural information on normal and
      diseased tissues. OCT is a promising emerging imaging modality for use in current
      pediatric patient populations.

PMID- 18322425
TI  - Symptom outcomes in endoscopic sinus surgery: a systematic review of measurement
      methods.
AB  - OBJECTIVE: To determine the type and prevalence of measurement methods used to
      analyze symptom outcomes after endoscopic sinus surgery (ESS). DATA SOURCES: Data
      were derived from PubMed, MEDLINE, EMBASE, Web of Science, Cochrane databases,
      Google Scholar, and manual searches. STUDY SELECTION: All English-language
      studies consisting of more than 10 adult patients from January 1980 to December
      2006 reporting ESS symptom outcome results were reviewed. Studies of radical
      surgery and studies involving patients with significant comorbidities were
      excluded. RESULTS: The ESS symptom outcome results of 29,333 patients were
      reported in 204 studies. Symptom outcome was determined by survey instruments in
      47 (23.0%) studies and individual symptom scoring in 63 (31%) studies. Of 18
      validated instruments used, almost two thirds of studies that reported results by
      survey measures used the following three instruments: Chronic Sinusitis Survey
      (12 studies), Sinonasal Outcome Test-20 (11 studies), and Medical Outcomes study
      36-Item Short-Form Health Survey (10 studies). The percentages of studies that
      reported specific results of the 1997 American Academy of Otolaryngology-Head
      Neck Surgery Rhinosinusitis Task Force (RSTF) chronic rhinosinusitis symptom
      criteria varied as follows: facial pain/pressure, 35%; facial
      congestion/fullness, 10%; nasal obstruction/blockage, 42%; nasal
      discharge/purulence/discolored postnasal discharge, 47%; hyposmia/anosmia, 35%;
      fever, 2%; halitosis, 4%; fatigue, 11%; dental pain, 3%; cough, 10%; and ear
      pain/pressure/fullness, 6%. CONCLUSIONS: ESS symptom outcome is assessed
      inconsistently by numerous measures. Individual report- ing of all RSTF chronic
      rhinosinusitis symptom criteria, as recommended by the RSTF and by subsequent
      consensus conferences, is rarely noted. Many RSTF symptom criteria are seldom
      studied.

PMID- 18322426
TI  - In reference to plasma radiofrequency preceded by pressure recording enhances
      success for treating sleep-related breathing disorders.

PMID- 18322427
TI  - In reference to effectiveness of adenotonsillectomy in the resolution of
      nocturnal enuresis secondary to obstructive sleep apnea.

PMID- 18322429
TI  - Neutralization of blood group A-antigen by a novel anti-A antibody: overcoming
      ABO-incompatible solid-organ transplantation.
AB  - BACKGROUND: The major barrier to ABO-incompatible solid-organ transplantation is
      acute humoral rejection. It is known to be triggered by antidonor blood group A/B
      antibodies, which might bind to A/B-antigen on the endothelium of the graft.
      Various strategies to reduce antiblood group antibody by overcoming ABO
      incompatible transplantation have been tried. However, antigen-suppressing
      procedures have not been performed. METHODS: We produced a novel anti-A antibody
      (K7508) by immunizing mice with salivary mucin of a blood group A individual,
      thereby clarifying that blood group A-antigen is expressed in endothelial cells
      of the liver. We investigated whether K7508 can mask A-antigen on the cells in
      vitro. Next, we immunized mice with A-antigen-expressing cells coated with K7508
      or its Fab fragment, and measured anti-A antibody production in the mice.
      RESULTS: Blood group A-antigen-expressing cells, such as blood group A-red blood
      cells (A-RBCs) and A431 cells, coated with K7508 were not recognized by another
      anti-A antibody in flow cytometry, indicating that A-antigen was masked by K7508
      in vitro. The A-antigen on the paraffin-embedded liver tissue was also masked by
      K7508. Furthermore, the production of anti-A antibody in mice immunized with A
      antigen-expressing cells coated with K7508 or its Fab fragment was significantly
      suppressed compared to that in mice immunized with non-coated cells alone,
      indicating that A-antigen was neutralized by K7508 in vivo. CONCLUSIONS: The
      neutralization of blood group antigen by antiblood group antibody and especially
      its Fab fragment might represent one strategy to overcome ABO-incompatible organ
      transplantation.

PMID- 18322430
TI  - B-cell concentration in the apheretic product predicts acute graft-versus-host
      disease and treatment-related mortality of allogeneic peripheral blood stem cell
      transplantation.
AB  - BACKGROUND: The influence of the graft composition on the clinical outcome after
      allogeneic peripheral blood stem cell (PBSC) transplantation is not well
      established. METHODS: The cellular composition of the apheretic products obtained
      from 63 human leukocyte antigen-identical siblings was prospectively correlated
      with the outcome of patients with hematological malignancies undergoing an
      allogeneic PBSC transplant after myeloablative conditioning. The concentration of
      nuclear, mononuclear, CD34+, T-cell subsets, B cells, and natural killer cells in
      the graft has been analyzed. RESULTS: In univariate analysis, acute graft-versus
      host disease (GVHD) correlated with the disease (P=0.002), with the phase of
      disease at transplant (P=0.01), and with the number of CD20+ cells infused
      (P=0.05). In multivariate analysis, a dose of CD20+ cells in the graft higher
      than the median dose remained the only factor negatively affecting the incidence
      of acute GVHD (P=0.01; 95% confidence interval [CI]: 0.12-0.78). In univariate
      analysis, treatment-related mortality (TRM) correlated with the disease (P=0.04)
      and was negatively affected by a dose of infused B cells greater than the median
      value (28% versus 50%; P=0.02). In multivariate analysis, TRM was close to
      statistical correlation with the dose of CD20+ cells (P=0.06; 95% CI: 0.02-1.05).
      No other clinical parameter was influenced by the composition of the graft.
      CONCLUSIONS: Our results suggest that the concentration of B cells in the
      apheretic product may predict the incidence of acute GVHD and TRM in patients
      undergoing an allogeneic PBSC transplantation and open the way to the new
      preventive and therapeutic strategies for the management of GVHD.

PMID- 18322431
TI  - The effect of kidney transplantation on distal tubular vacuolar H+-ATPase.
AB  - BACKGROUND: The presence of vacuolar (v)H+-ATPase in distal tubule alpha
      intercalated cells is essential for hydrogen excretion and maintenance of acid
      base homeostasis. Loss of vH+-ATPase after kidney transplantation could cause
      posttransplant distal renal tubular acidosis (dRTA). METHOD: Immunostaining of
      the kidney specific vH+-ATPase of cortical collecting duct cells (CCT) was
      performed in 37 kidney biopsies taken immediately prior to transplantation and
      after engraftment (median [range]: 10 [1-181] months). Apical or
      intracytoplasmatic staining intensity was classified as grade 0 (absent), grade 1
      (weak), or grade 2 (strong), and positive cells expressed as percentage of all
      CCT cells. In addition, kidney biopsies were scored for damage by the Banff
      schema. Serum and urinary pH, anion gap, and serum potassium were obtained for
      the diagnoses of dRTA. RESULTS: Fourteen transplant recipients had dRTA type I, 5
      had rate-limited RTA, six had type IV dRTA, and 12 had no RTA. In pretransplant
      biopsies, 40% [3-77%] of CCT cells were positive for vH+-ATPase but only 17% [0
      39%] after transplantation (P<0.0001). The loss of vH+-ATPase expression was
      similar in patients with dRTA type I (-21%), type IV (-25%), rate limited RTA (
      21%), or no RTA (-29%). The decrease affected predominantly the apical proton
      pump expression. The individual loss of vH+-ATPase expression was not related to
      the time elapsed since transplantation, immunosuppressive drugs, acute transplant
      rejection, or tubulointerstitial changes. CONCLUSION: Kidney transplantation
      leads to a general decrease of distal tubular vH+-ATPase expression. Loss of
      proton pump activity occurs unrelated to immunosuppressive therapy or transplant
      related histologic changes.

PMID- 18322432
TI  - Living donor liver transplantation for hepatocellular carcinoma: a single-center
      experience in Taiwan.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) demonstrates certain
      survival benefits over deceased donor liver transplantation for hepatocellular
      carcinoma (HCC) but there is no consensus on criteria for the use of LDLT for HCC
      for hepatocellular carcinoma (HCC) taking into account strategies to improve
      survival. METHODS: Thirty-five patients (89% men) underwent LDLT for HCC. The
      mean age was 51 years (range, 22-61). The median disease severity scores were B,
      11-20, and 2B for Child-Turcotte-Pugh, Model for End-stage Liver Disease, and
      United Network for Organ Sharing, respectively. The transplant records were
      retrospectively analyzed. RESULTS: All were within Milan criteria at time of
      transplantation. A novel approach to downstaging tumors initially beyond the
      Milan criteria was evaluated using transarterial embolization or percutaneous
      ethanol injection. Our initial results were encouraging as recipients whose
      tumors had been downstaged had not had recurrence to date. Seven (20%) patients
      underwent hepatectomy for HCC before undergoing transplant. The overall mean
      posttransplant follow-up in this series was 40.3 months (range, 23-75). The
      overall posttransplant complication rate requiring intervention was 11%. There
      was only one malignancy recurrence for an overall recurrence rate of 3%. Vascular
      invasion and small- for-size transplants did not seem to influence tumor
      recurrence. The nonestimated recipient 1-year, 3-year, and 5-year survivals were
      98%, 96%, and 90%, respectively. CONCLUSION: This review emphasizes the need for
      early disease recognition and prompt intervention when Milan criteria are met to
      improve survival from HCC after LDLT.

PMID- 18322433
TI  - Variations in the assessment practice for renal transplantation across the United
      Kingdom.
AB  - BACKGROUND: To investigate whether there are any variations in the evaluation of
      adult candidates for cadaveric renal transplantation among transplant centers in
      the United Kingdom. METHODS: An online survey of transplant units in the United
      Kingdom, including nephrologists, surgeons, and transplant coordinators, measured
      differences in the assessment process and evaluation of patient's age, body mass
      index (BMI), cardiovascular comorbidity, and viral serology. RESULTS: A response
      was received from 20 out of the 23 centers (87%). These centers perform 90% of
      all renal transplants in the United Kingdom. In 30% of the units, there is no
      formal transplant assessment clinic. There is no cutoff age limit for assessment
      across the United Kingdom, but 12 centers (60%) exclude patients with a high BMI,
      with a median cutoff BMI of 35. Eight out of the 20 centers do not give
      cytomegalovirus (CMV)-negative patients the option to receive kidneys from a CMV
      positive donor. Hepatitis C antibody-positive donors are not used in 50% of the
      units. There is considerable variation in the investigation of cardiovascular
      disease and exclusion criteria based on cardiovascular status of the patients.
      Five units have no consistent policy of re-evaluating patients once they are
      listed. CONCLUSIONS: There is evidence, from this study, of significant
      variations in the assessment of patients for renal transplantation across the
      United Kingdom. Further research and better-defined guidelines are required for a
      uniform assessment process and to ensure equity of access to the renal transplant
      waiting list.

PMID- 18322434
TI  - HLA mismatches remain risk factors for acute kidney allograft rejection in
      patients receiving quadruple immunosuppression with anti-interleukin-2 receptor
      antibodies.
AB  - BACKGROUND: New immunosuppressive drugs such as anti-interleukin-2 receptor
      antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of
      acute rejection after renal transplantation. Whether matching donor and recipient
      human leukocyte antigen (HLA) antigens is still relevant in patients receiving
      modern immunosuppression has been questioned. METHODS: We retrospectively
      analyzed the incidence and risk factors of acute rejection during the first
      posttransplant year and the impact of acute rejection on long-term graft survival
      in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab,
      n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin,
      n=28), mycophenolate mofetil, and steroids. Graft and patient survival were
      calculated by the Kaplan-Meier method. Risk factors for acute rejection were
      analyzed by logistic regression modeling. RESULTS: Twenty-seven patients were
      treated for acute rejection (26 biopsy-proven) during the first posttransplant
      year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The
      number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods
      of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis)
      were the only independent risk factors for first-year acute rejection. First-year
      acute rejection was associated with a significant reduction in overall and death
      censored graft survival at 5 years after transplantation. CONCLUSIONS: Although
      infrequent in patients receiving modern immunosuppressive drugs, acute rejection
      remains an important risk factor for graft loss after renal transplantation. Our
      results suggest that better HLA matching and shorter periods of dialysis before
      transplantation could reduce acute rejection rates and further improve outcomes
      under current immunosuppressive regimens.

PMID- 18322435
TI  - Lung transplant ischemia reperfusion injury: metalloprotease inhibition down
      regulates exposure of type V collagen, growth-related oncogene-induced neutrophil
      chemotaxis, and tumor necrosis factor-alpha expression.
AB  - BACKGROUND: Immunity to type V collagen [col(V)] contributes to lung transplant
      rejection. Matrix metalloproteases (MMPs), which are induced by transplant
      related ischemia-reperfusion injury (IRI), could expose col(V) and regulate local
      IRI-induced inflammation. METHODS: To test the hypothesis that MMPs induce col(V)
      exposure and inflammation, Wistar-Kyoto rats were treated with the MMP inhibitor,
      COL-3, before inducing lung IRI without transplantation, and in parallel studies,
      Wistar-Kyoto lung donor and recipients were treated with COL-3 pre- and
      postisograft lung transplantation. RESULTS: Ischemia-reperfusion injury induced
      growth-related oncogene/CINC-1-dependent neutrophil influx, and up-regulated
      tumor necrosis factor-alpha. MMP2 and MMP9, induced at 4 and 24 hr after IRI,
      respectively, were associated with detection of antigenic col(V) in
      bronchoalveolar lavage and lung interstitium because of MMP-mediated matrix
      degradation. MMP-inhibitor treatment significantly reduced polymorphonuclear
      leukocytes, growth-related oncogene/CINC-1, and tumor necrosis factor-alpha;
      abrogated MMP-9 expression; and resulted in lower levels of antigenic col(V) in
      bronchoalveolar lavage. In the lung transplant model, inhibiting MMPs in the
      donor before lung harvest and in the recipient after lung transplantation
      resulted in improved oxygenation and diminished polymorphonuclear leukocyte
      influx into the isograft. CONCLUSION: MMP inhibition may be a potential therapy
      to prevent release of antigenic col(V) and ameliorate IRI in the transplant
      recipient.

PMID- 18322436
TI  - Adjuvant approaches to renal cell carcinoma.

PMID- 18322437
TI  - Advances in the use of alemtuzumab in CLL.

PMID- 18322438
TI  - Update on the management of von Willebrand disease.

PMID- 18322439
TI  - Novel targets for systemic therapy of colorectal cancer.

PMID- 18322440
TI  - Advances and challenges in the use of biomarkers in clinical trials.

PMID- 18322441
TI  - Biologic study of the effects of octreotide-LAR on growth hormone in unresectable
      and metastatic hepatocellular carcinoma.
AB  - BACKGROUND: Animal models suggest that growth hormone participates in
      hepatocarcinogenesis. OBJECTIVE: To correlate the effect of octreotide long
      acting release (LAR) on insulin-like growth factor-I (IGF-I) and -II (IGF-II)
      with response and survival in patients with unresectable and metastatic
      hepatocellular carcinoma. METHODS: We conducted a phase II, single-institution
      trial of octreotide-LAR (30 mg intramuscularly every 4 weeks) in 15 patients
      while monitoring serum IGF-I and -II levels. RESULTS: Patients (median CLIP score
      2, Okuda stage II, and ECOG performance status 1) were treated for a median of
      2.0 cycles. No responses occurred. Median overall survival was 116 days (range,
      27-937 days) and median progression-free survival was 60 days (range, 27-444
      days). One patient had prolonged stable disease (16 months). There were no grade
      4 and four grade 3 toxicities: abdominal cramping, elevated creatinine, diarrhea,
      and dyspnea. Median serum IGF-I decreased from baseline (42.2 ng/mL; range, 14.2
      109 ng/mL) to day 29 (27.9 ng/mL; range, 5.7-71.1 ng/mL), and median serum IGF-II
      decreased from baseline (25,000 ng/mL; range, 12,400-93,600 ng/mL) to day 29
      (18,400 ng/mL; range, 4,061-79,400 ng/mL; 2-sided P<.006 and P<.04, respectively;
      Wilcoxon signed rank test). This suppression did not correlate with clinical
      activity. Baseline serum IGF-I >30 ng/mL was associated with greater progression
      free survival and overall survival (P=.0005 and P=.0173, respectively; 2-sided
      log-rank test). CONCLUSIONS: Octreotide-LAR lowered serum IGF-I and -II levels;
      however, this lowering did not correlate with clinical activity. There were no
      responses, and progression-free survival and overall survival were similar to
      historical patients not on treatment. Baseline serum IGF-I predicted prognosis.

PMID- 18322442
TI  - ZAP-70 protein expression and CD38 positivity in B-cell chronic lymphocytic
      leukemia.
AB  - BACKGROUND: The clinical course, disease progression, and survival of B-cell
      chronic lymphocytic leukemia (B-CLL) have been correlated with immunoglobulin
      heavy-chain variable region mutation status. The biologic parameters 70-kDa zeta
      associated protein (ZAP-70) and CD38 expression are easier and faster surrogate
      markers for mutational status. OBJECTIVE: To assess retrospectively ZAP-70
      expression in B-CLL cells using flow cytometry and examine its relationship with
      CD38 expression and the median time from diagnosis to initial therapy. METHODS:
      Ninety-four unselected patients who had their follow-up in the outpatient clinic
      from 2004 to 2005 were reviewed for immunophenotyping ZAP-70 and CD38 expression.
      Direct immunolabeling with clone 2E3.2, isotype IgG2a, enabled easy
      quantification of ZAP-70 by flow cytometry in association with CD38 expression;
      in addition, the mean fluorescence intensity ratio (MFIR) of CD19+CD5+ B-CLL
      cells compared to an isotype control monoclonal antibody was determined. RESULTS:
      ZAP-70 expression levels in B-CLL cells varied widely (0.3-99%). The median time
      to therapy was significantly shorter for the 54 patients with 20% or more ZAP-70+
      cells (30 months) than for the 40 patients with less than 20% ZAP-70+ cells
      (median time to treatment not reached). The optimal MFIR for classifying patients
      as ZAP-70+ was 2. Thirty-two patients had a threshold of ZAP-70+CD38+ greater
      than 30%, with a median time from diagnosis to treatment of 19 months. Regardless
      of CD38 expression level, CD38 and ZAP-70 expressions were significantly
      associated. The median interval from diagnosis to initial therapy was 16.2 months
      for ZAP-70+CD38+ patients, 60 months for ZAP-70+CD38- or ZAP-70-CD38+ patients,
      and had not yet been reached for ZAP-70-CD38- patients. CONCLUSION: The
      association of ZAP-70+CD19+CD5+ B-CLL cells and percentage of CD38+CD19+CD5+ B
      CLL cells evaluated by flow cytometry provide reliable methods that could be
      introduced into a routine diagnostic B-CLL panel to predict outcome.

PMID- 18322443
TI  - New strategies in the treatment of T-cell lymphoma.
AB  - A Review of Selected Presentations From the 43rd American Society of Clinical
      Oncology Annual Meeting, June 1-5, 2007, Chicago, Illinois.

PMID- 18322444
TI  - Self-reported falls and fall-related injuries among persons aged > or =65 years-
      United States, 2006.
AB  - Each year, an estimated one third of older adults fall, and the likelihood of
      falling increases substantially with advancing age. In 2005, a total of 15,802
      persons aged > or =65 years died as a result of injuries from falls. However, the
      number of older adults who fall and are not injured or who sustain minor or
      moderate injuries and seek treatment in clinics or physician offices is unknown.
      To estimate the percentage of older adults who fell during the preceding 3
      months, CDC analyzed data from the 2006 Behavioral Risk Factor Surveillance
      System (BRFSS) survey. This report summarizes the results of that analysis, which
      indicated that approximately 5.8 million persons aged > or =65 years, or 15.9% of
      all U.S. adults in that age group, fell at least once during the preceding 3
      months, and 1.8 million (31.3%) of those who fell sustained an injury that
      resulted in a doctor visit or restricted activity for at least 1 day. The
      percentages of women and men who fell during the preceding 3 months were similar
      (16.4% versus 15.2%, respectively), but women reported significantly more fall
      related injuries than men (35.7% versus 24.6%, respectively). The effect these
      injuries have on the quality of life of older adults and on the U.S. health-care
      system reinforces the need for broader use of scientifically proven fall
      prevention interventions.

PMID- 18322445
TI  - Cost of vaccinating refugees overseas versus after arrival in the United States,
      2005.
AB  - Since 2000, approximately 50,000 refugees have entered the United States each
      year from various regions of the world. Although persons with immigrant status
      are legally required to be vaccinated before entering the United States, this
      requirement does not extend to U.S.-bound persons with refugee status. After 1
      year in the United States, refugees can apply for a change of status to that of
      legal permanent resident, at which time they are required to be fully vaccinated
      in accordance with recommendations of the Advisory Committee on Immunization
      Practices (ACIP). A potentially less costly alternative might be to vaccinate
      U.S.-bound refugees overseas routinely, before they depart from refugee camps. To
      compare the cost of vaccinating refugees overseas versus after their arrival in
      the United States, CDC analyzed 2005 data on the number of refugees, cost of
      vaccine, and cost of vaccine administration. This report summarizes the results
      of that analysis, which suggested that, in 2005, vaccinating 50,787 refugees
      overseas would have cost an estimated $7.7 million, less than one third of the
      estimated $26.0 million cost of vaccinating in the United States. Costs were
      calculated from the perspective of the U.S. health-care system. To achieve public
      health cost savings, routine overseas vaccination of U.S.-bound refugees should
      be considered.

PMID- 18322446
TI  - U.S.-incurred costs of wild poliovirus infections in a camp with U.S.-bound
      refugees--Kenya, 2006.
AB  - Routine predeparture vaccinations are not required for U.S.-bound refugees, a
      policy that potentially leaves U.S. communities vulnerable to importation of
      vaccine-preventable diseases. During October-December 2006, an outbreak of
      poliomyelitis associated with wild poliovirus type 1 (WPV1) occurred in a camp
      occupied by refugees awaiting resettlement to the United States. This report
      describes the costs of domestic and international activities borne by U.S.
      federal and state governments, U.S.-funded organizations, and U.S. voluntary
      agencies during their response to this outbreak. Requiring predeparture polio
      vaccinations for U.S.-bound refugees might reduce the risk for poliovirus
      importation and reduce the costs associated with responses to polio outbreaks
      among refugees.

PMID- 18322447
TI  - Appealing to the restless consumer.

PMID- 18322448
TI  - Influence of CYP3A4, CYP3A5, and ABCB1 genotype and expression on budesonide
      pharmacokinetics: a possible role of intestinal CYP3A4 expression.
AB  - Budesonide treatment of chronic inflammatory bowel disease commonly leads to non
      response or adverse reactions, possibly because of alterations in efflux
      transport mediated by the ABCB1 gene product P-glycoprotein or metabolism by
      CYP3A isoenzymes. Two groups, each consisting of nine healthy volunteers, one
      with the CYP3A5(*)1/(*)3 genotype (expressors) and the other with the
      CYP3A5(*)3/(*)3 genotype (non-expressors), were given a single oral dose of 9 mg
      budesonide. Plasma and urine concentrations of budesonide and its major
      metabolites were determined using liquid chromatography-tandem mass spectrometry.
      Subsequently, rectosigmoidal biopsies were taken for analysis of messenger RNA
      (mRNA) expression. Budesonide pharmacokinetics did not differ between genotype
      groups. However, intestinal CYP3A4 expression was shown to correlate directly
      with partial metabolic clearances of 16-hydroxy-prednisolone (r(2) = 0.30; P =
      0.010) and 6-hydroxy-budesonide (r(2) = 0.25; P = 0.016), but inversely with
      budesonide AUC(0-24 h) (r(2) = 0.18; P = 0.040). Interestingly, a strong
      correlation was found between CYP3A5 and ABCB1 expression in CYP3A5 expressors
      (r(2) = 0.79; P = 0.001). This study suggests that intestinal CYP3A4 expression
      has an impact on budesonide pharmacokinetics. Moreover, CYP3A5 and ABCB1
      expression appears to be coregulated.

PMID- 18322449
TI  - Blood lead levels and bone turnover with weight reduction in women.
AB  - High bone turnover states are known to raise blood lead levels (BPb). Caloric
      restriction will increase bone turnover, yet it remains unknown if weight
      reduction increases BPb due to mobilization of skeletal stores. We measured whole
      blood Pb levels ((206)Pb) by inductively coupled plasma mass spectrometry in 73
      women (age 24-75 years; BMI 23- 61 kg/m(2)) before and after 6 months of severe
      weight loss (S-WL), moderate weight loss (M-WL), or weight maintenance (WM).
      Baseline BPb levels were relatively low at 0.2-6.0 microg/dl, and directly
      associated with age (r=0.49, P<0.0001). After severe WL (-37.4+/-9.3 kg, n=17),
      BPb increased by 2.1+/-3.9 microg/dl (P<0.05), resulting in BPb levels of 1.3
      12.5 microg/dl. M-WL (-5.6+/-2.7 kg, n=39) and WM (0.3+/-1.3 kg, n=17) did not
      result in an increase in BPb levels (0.5+/-3.2 and 0.0+/-0.7 microg/dl, M-WL and
      WM, respectively). BPb levels increased more with greater WL (r=0.24, P<0.05).
      Bone turnover markers increased only with severe WL and were directly correlated
      with WL. At baseline, higher calcium intake was associated with lower BPb (r=
      0.273, P<0.02), however, this association was no longer present after 6 months.
      Severe weight reduction in obese women increases skeletal bone mobilization and
      BPb, but values remain well below levels defined as Pb overexposure.

PMID- 18322450
TI  - On exposure and response relationships for health effects associated with
      exposure to vehicular traffic.
AB  - This work examines various metrics and models that have been used to estimate
      long-term health effects of exposure to vehicular traffic. Such health impacts
      may include effects of air pollution due to emissions of combustion products and
      from vehicle or roadway wear, of noise, stress, or from socioeconomic effects
      associated with preferred residential locations. Both categorical and continuous
      exposure metrics are considered, typically for distances between residences and
      roadways, or for traffic density or intensity. It appears that continuous
      measures of exposure tend to yield lower risk estimates that are also more
      precise than categorical measures based on arbitrary criteria. The selection of
      appropriate exposure increments to characterize relative risks is also important
      in comparing pollutants and other agents. Confounding and surrogate variables are
      also important issues, since studies of traffic proximity or density cannot
      identify the specific agents related to traffic exposures that might be
      responsible for the various health endpoints that have been implicated. Studies
      based on ambient air quality measurements are necessarily restricted to species
      for which data are available, some of which may be serving as markers for the
      actual agents of harm. Studies based on modeled air quality are limited by the
      accuracy of mobile source emission inventories, which may not include poorly
      maintained (high emitting) vehicles. Additional exposure modeling errors may
      result from precision limitations of geocoding methods. Studies of the health
      effects of traffic are progressing from establishing the existence of
      relationships to describing them in more detail, but effective remedies or
      control strategies have generally not yet been proposed in the context of these
      epidemiological studies. Resolution of these dose-response uncertainties is
      important for the development of effective public health strategies for the
      future.

PMID- 18322451
TI  - Tracking personal exposure to particulate diesel exhaust in a diesel freight
      terminal using organic tracer analysis.
AB  - Personal exposure to particle-phase molecular markers was measured at a trucking
      terminal in St Louis, MO, as part of a larger epidemiologic project aimed at
      assessing carbonaceous fine particulate matter (PM) exposure in this occupational
      setting. The integration of parallel personal exposure, ambient worksite area and
      ambient urban background (St Louis Supersite) measurements provided a unique
      opportunity to track the work-related exposure to carbonaceous fine PM in a
      freight terminal. The data were used to test the proposed personal exposure model
      in this occupational setting: To accurately assess the impact of PM emission
      sources, particularly motor vehicle exhaust, and organic elemental carbon (OCEC)
      analysis and nonpolar organic molecular marker analysis by thermal desorption-gas
      chromatography/mass spectrometry (TD-GCMS) were conducted on all of the PM
      samples. EC has been used as a tracer for diesel exhaust in urban areas, however,
      the emission profile for diesel exhaust is dependent upon the operating
      conditions of the vehicle and can vary considerably within a fleet. Hopanes,
      steranes, polycyclic aromatic hydrocarbons and alkanes were measured by TD-GCMS.
      Hopanes are source-specific organic molecular markers for lubricating oil present
      in motor vehicle exhaust. The concentrations of OC, EC and the organic tracers
      were averaged to obtain average profiles to assess differences in the personal,
      worksite area and urban background samples, and were also correlated individually
      by sample time to evaluate the exposure model presented above. Finally, a
      chemical mass balance model was used to apportion the motor vehicle and cigarette
      smoke components of the measured OC and EC for the average personal exposure,
      worksite area and urban background samples.

PMID- 18322452
TI  - Genome-wide search for QTLs for apolipoprotein A-I level in elderly Swedish DZ
      twins: evidence of female-specific locus on 15q11-13.
AB  - The effect of genetic variants underlying atherosclerosis is thought to be
      mediated through intermediate phenotypes such as serum cholesterol levels.
      Localization of quantitative trait loci influencing levels of serum lipids and
      (apo)lipoproteins may aid in the search for determinants of susceptibility to
      atherosclerotic diseases. Since apolipoprotein A-I is the primary protein
      constituent of high-density lipoprotein, it is considered to be critical for the
      antiatherogenic effect of high-density lipoproteins. We describe here an effort
      to map loci influencing apolipoprotein A-I levels. Measurements of apolipoprotein
      A-I levels and genome scans with more than 1000 microsatellite markers were
      successfully performed in both members of 501 pairs of fraternal twins from
      Sweden. Variance component linkage analysis was undertaken to map quantitative
      trait loci. In the total study sample, two loci showed comparable suggestive
      evidence of linkage, 6p21-12 (LOD=2.4) and 12q23 (LOD=2.4). Sex-limited analyses
      revealed significant female-specific linkage at marker D15S156 on 15q11-13
      (LOD=4.1). The loci on 12q and 15q in the present study confirm previously
      reported loci for apolipoprotein A-I, while the peak on chromosome 6p lends
      further support to a locus influencing several phenotypes related to
      atherosclerosis. Intriguingly, the presence of genes belonging to the
      phospholipase A2 superfamily under three out of four observed linkage peaks would
      lend some support to the view that this group of genes might collectively
      represent candidates as apolipoprotein A-I level regulators.

PMID- 18322453
TI  - Quantifying the increase in average human heterozygosity due to urbanisation.
AB  - The human population is undergoing a major transition from a historical
      metapopulation structure of relatively isolated small communities to an outbred
      structure. This process is predicted to increase average individual genome-wide
      heterozygosity (h) and could have effects on health. We attempted to quantify
      this increase in mean h. We initially sampled 1001 examinees from a
      metapopulation of nine isolated villages on five Dalmatian islands (Croatia).
      Village populations had high levels of genetic differentiation, endogamy and
      consanguinity. We then selected 166 individuals with highly specific personal
      genetic histories to form six subsamples, which could be ranked a priori by their
      predicted level of outbreeding. The measure h was then estimated in the 166
      examinees by genotyping 1184 STR/indel markers and using two different
      computation methods. Compared to the value of mean h in the least outbred sample,
      values of h in the remaining samples increased successively with predicted
      outbreeding by 0.023, 0.038, 0.058, 0.067 and 0.079 (P<0.0001), where these
      values are measured on the same scale as the inbreeding coefficient (but opposite
      sign). We have shown that urbanisation was associated with an average increase in
      h of up to 0.08-0.10 in this Croatian metapopulation, regardless of the method
      used. Similar levels of differentiation have been described in many populations.
      Therefore, changes in the level of heterozygosity across the genome of this
      magnitude may be common during isolate break-up in humans and could have
      significant health effects through the established genetic mechanism of hybrid
      vigour/heterosis.

PMID- 18322454
TI  - Homozygosity mapping in a family presenting with schizophrenia, epilepsy and
      hearing impairment.
AB  - Homozygosity mapping within consanguineous families is a powerful method of
      localising genes for autosomal recessive disease. We investigated a family from
      Punjab, Pakistan, a region where consanguineous marriages are frequent. The
      parents have no detectable clinical disorders. However, five out of six children
      present with schizophrenia, epilepsy or hearing impairment either alone or in
      combination. This unusual phenotype in several offspring of first cousins is
      strongly suggestive of a rare, Mendelian recessive disorder. Two genome-wide
      scans initially using low-density microsatellites, and subsequently high-density
      SNP markers were used to map homozygous-by-descent regions in affected
      individuals. Candidate genes within these loci were subsequently screened for
      mutations. Homozygosity analysis and inbreeding coefficients were investigated to
      give an estimate of consanguinity. Two putative disease loci were mapped to
      22q12.3-q13.3 and 2p24.3. The candidate locus on chromosome 2p24 overlaps with a
      deafness locus, DFNB47, linked to autosomal recessive hearing impairment, while
      positive findings reported for affective psychosis and schizophrenia cluster in a
      region of 4-5 cM on 22q13.1 within our second candidate locus. Sequence analysis
      of three candidate genes (KCNF1 (2p); ATF4, CACNG2 (22q)) did not reveal any
      exonic mutations. Inbreeding coefficients calculated for each family member
      support a very high degree of ancestral and recent inbreeding. The screening of
      other candidate genes located within these newly identified disease intervals on
      Chr2p24.3 and 22q12.3-q13.3 may lead to the discovery of causative variants, and
      consequent disrupted molecular pathways associated with this rare phenotype.

PMID- 18322456
TI  - Is the zinc intake of young people in the UK adequate?

PMID- 18322457
TI  - Genetic evidence and the modern human origins debate.
AB  - A continued debate in anthropology concerns the evolutionary origin of
      'anatomically modern humans' (Homo sapiens sapiens). Different models have been
      proposed to examine the related questions of (1) where and when anatomically
      modern humans first appeared and (2) the genetic and evolutionary relationship
      between modern humans and earlier human populations. Genetic data have been
      increasingly used to address these questions. Genetic data on living human
      populations have been used to reconstruct the evolutionary history of the human
      species by considering how global patterns of human variation could be produced
      given different evolutionary scenarios. Of particular interest are gene trees
      that reconstruct the time and place of the most recent common ancestor of
      humanity for a given haplotype and the analysis of regional differences in
      genetic diversity. Ancient DNA has also allowed a direct assessment of genetic
      variation in European Neandertals. Together with the fossil record, genetic data
      provide insight into the origin of modern humans. The evidence points to an
      African origin of modern humans dating back to 200,000 years followed by later
      expansions of moderns out of Africa across the Old World. What is less clear is
      what happened when these early modern humans met preexisting 'archaic human'
      populations outside of Africa. At present, it is difficult to distinguish between
      a model of total genetic replacement and a model that includes some degree of
      genetic mixture.

PMID- 18322458
TI  - Sex-specific crossover patterns in Zebrafish (Danio rerio).
AB  - Some species display intersex variation in their rate of meiotic recombination,
      where recombination is usually suppressed in the heterogametic sex. Although no
      heteromorphic sex chromosomes have been detected in zebrafish (Danio rerio),
      genetic analysis has indicated a lower frequency of recombination in males
      relative to females. Our study of the meiotic recombination pattern in female
      zebrafish indicates that adult females have only a few meiotic oocytes that are
      found in groups in the ventral zone of the ovarian surface. We used antibody
      staining of human mutL homolog 1 (MLH1) protein to mark the sites of putative
      chiasmata to seek a physical basis for the pattern of recombination and its
      relative frequency in both sexes. We report that MLH1 foci are found mostly in
      distal regions of the synaptonemal complexes (SCs) in males, but tend to be more
      evenly distributed in females. Our cytological analysis yields a ratio of MLH1
      foci per chromosome in males versus females of 1:1.55. This lower level of
      recombination in males is in general agreement with previously published results
      from linkage map analysis. However, the similar ratio of MLH1 foci per unit
      length of SCs in both sexes demonstrates a correlation between SC length and the
      frequency of recombination rather than a mechanism that suppresses recombination
      in males. Thus, chiasma interference seems to provide similar expression in males
      and females in agreement with the situation in humans, where oocytes with longer
      SCs display a higher level of recombination that is not a consequence of more
      closely spaced crossovers along the SCs.

PMID- 18322459
TI  - On the origin of the genetic code: signatures of its primordial complementarity
      in tRNAs and aminoacyl-tRNA synthetases.
AB  - If the table of the genetic code is rearranged to put complementary codons face
      to-face, it becomes apparent that the code displays latent mirror symmetry with
      respect to two sterically different modes of tRNA recognition. These modes
      involve distinct classes of aminoacyl-tRNA synthetases (aaRSs I and II) with
      recognition from the minor or major groove sides of the acceptor stem,
      respectively. We analyze the anticodon pairs complementary to the face-to-face
      codon couplets. Taking into account the invariant nucleotides on either side (5'
      and 3'), we consider the risk of anticodon confusion and subsequent erroneous
      aminoacylation in the ancestral coding system. This logic leads to the conclusion
      that ribozymic precursors of tRNA synthetases had the same two complementary
      modes of tRNA aminoacylation. This surprising case of molecular mimicry (1) shows
      a key potential selective advantage arising from the partitioning of aaRSs into
      two classes, (2) is consistent with the hypothesis that the two aaRS classes were
      originally encoded by the complementary strands of the same primordial gene and
      (3) provides a 'missing link' between the classic genetic code, embodied in the
      anticodon, and the second, or RNA operational, code that is embodied mostly in
      the acceptor stem and is directly responsible for proper tRNA aminoacylation.

PMID- 18322460
TI  - Isolation of an active step I spliceosome and composition of its RNP core.
AB  - Formation of catalytically active RNA structures within the spliceosome requires
      the assistance of proteins. However, little is known about the number and nature
      of proteins needed to establish and maintain the spliceosome's active site. Here
      we affinity-purified human spliceosomal C complexes and show that they catalyse
      exon ligation in the absence of added factors. Comparisons of the composition of
      the precatalytic versus the catalytic spliceosome revealed a marked exchange of
      proteins during the transition from the B to the C complex, with apparent
      stabilization of Prp19-CDC5 complex proteins and destabilization of SF3a/b
      proteins. Disruption of purified C complexes led to the isolation of a salt
      stable ribonucleoprotein (RNP) core that contained both splicing intermediates
      and U2, U5 and U6 small nuclear RNA plus predominantly U5 and human Prp19-CDC5
      proteins and Prp19-related factors. Our data provide insights into the
      spliceosome's catalytic RNP domain and indicate a central role for the
      aforementioned proteins in sustaining its catalytically active structure.

PMID- 18322461
TI  - X-ray structure of a prokaryotic pentameric ligand-gated ion channel.
AB  - Pentameric ligand-gated ion channels (pLGICs) are key players in the early events
      of electrical signal transduction at chemical synapses. The family codes for a
      structurally conserved scaffold of channel proteins that open in response to the
      binding of neurotransmitter molecules. All proteins share a pentameric
      organization of identical or related subunits that consist of an extracellular
      ligand-binding domain followed by a transmembrane channel domain. The nicotinic
      acetylcholine receptor (nAChR) is the most thoroughly studied member of the pLGIC
      family (for recent reviews see refs 1-3). Two sources of structural information
      provided an architectural framework for the family. The structure of the soluble
      acetylcholine-binding protein (AChBP) defined the organization of the
      extracellular domain and revealed the chemical basis of ligand interaction.
      Electron microscopy studies of the nAChR from Torpedo electric ray have yielded a
      picture of the full-length protein and have recently led to the interpretation of
      an electron density map at 4.0 A resolution. Despite the wealth of experimental
      information, high-resolution structures of any family member have so far not been
      available. Until recently, the pLGICs were believed to be only expressed in
      multicellular eukaryotic organisms. The abundance of prokaryotic genome
      sequences, however, allowed the identification of several homologous proteins in
      bacterial sources. Here we present the X-ray structure of a prokaryotic pLGIC
      from the bacterium Erwinia chrysanthemi (ELIC) at 3.3 A resolution. Our study
      reveals the first structure of a pLGIC at high resolution and provides an
      important model system for the investigation of the general mechanisms of ion
      permeation and gating within the family.

PMID- 18322462
TI  - Identifying natural images from human brain activity.
AB  - A challenging goal in neuroscience is to be able to read out, or decode, mental
      content from brain activity. Recent functional magnetic resonance imaging (fMRI)
      studies have decoded orientation, position and object category from activity in
      visual cortex. However, these studies typically used relatively simple stimuli
      (for example, gratings) or images drawn from fixed categories (for example,
      faces, houses), and decoding was based on previous measurements of brain activity
      evoked by those same stimuli or categories. To overcome these limitations, here
      we develop a decoding method based on quantitative receptive-field models that
      characterize the relationship between visual stimuli and fMRI activity in early
      visual areas. These models describe the tuning of individual voxels for space,
      orientation and spatial frequency, and are estimated directly from responses
      evoked by natural images. We show that these receptive-field models make it
      possible to identify, from a large set of completely novel natural images, which
      specific image was seen by an observer. Identification is not a mere consequence
      of the retinotopic organization of visual areas; simpler receptive-field models
      that describe only spatial tuning yield much poorer identification performance.
      Our results suggest that it may soon be possible to reconstruct a picture of a
      person's visual experience from measurements of brain activity alone.

PMID- 18322463
TI  - Memory CD4 T cells emerge from effector T-cell progenitors.
AB  - A hallmark of adaptive immunity is the generation of memory T cells that confer
      long-lived, antigen-specific protection against repeat challenges by pathogens.
      Understanding the mechanisms by which memory T cells arise is important for
      rational vaccination strategies and improved therapeutic interventions for
      chronic infections and autoimmune disorders. The large clonal expansion of CD8 T
      cells in response to some infections has made the development of CD8 T-cell
      memory more amenable to study, giving rise to a model of memory cell
      differentiation in which a fraction of fully competent effector T cells
      transition into long-lived memory T cells. Delineation of CD4 T-cell memory
      development has proved more difficult as a result of limitations on tracking the
      smaller populations of CD4 effector T cells generated during a pathogenic
      challenge, complicating efforts to determine whether CD4 memory T cells are
      direct descendants of effector T cells or whether they develop by alternative
      pathways. Here, using two complementary cytokine reporter mouse models to
      identify interferon (IFN)-gamma-positive effector T cells and track their fate,
      we show that the lineage relationship between effector and memory CD4 T cells
      resembles that for CD8 T cells responding to the same pathogen. We find that, in
      parallel with effector CD8 T cells, IFN-gamma-positive effector CD4 T cells give
      rise to long-lived memory T cells capable of anamnestic responses to antigenic
      rechallenge.

PMID- 18322464
TI  - Broad phylogenomic sampling improves resolution of the animal tree of life.
AB  - Long-held ideas regarding the evolutionary relationships among animals have
      recently been upended by sometimes controversial hypotheses based largely on
      insights from molecular data. These new hypotheses include a clade of moulting
      animals (Ecdysozoa) and the close relationship of the lophophorates to molluscs
      and annelids (Lophotrochozoa). Many relationships remain disputed, including
      those that are required to polarize key features of character evolution, and
      support for deep nodes is often low. Phylogenomic approaches, which use data from
      many genes, have shown promise for resolving deep animal relationships, but are
      hindered by a lack of data from many important groups. Here we report a total of
      39.9 Mb of expressed sequence tags from 29 animals belonging to 21 phyla,
      including 11 phyla previously lacking genomic or expressed-sequence-tag data.
      Analysed in combination with existing sequences, our data reinforce several
      previously identified clades that split deeply in the animal tree (including
      Protostomia, Ecdysozoa and Lophotrochozoa), unambiguously resolve multiple long
      standing issues for which there was strong conflicting support in earlier studies
      with less data (such as velvet worms rather than tardigrades as the sister group
      of arthropods), and provide molecular support for the monophyly of molluscs, a
      group long recognized by morphologists. In addition, we find strong support for
      several new hypotheses. These include a clade that unites annelids (including
      sipunculans and echiurans) with nemerteans, phoronids and brachiopods, molluscs
      as sister to that assemblage, and the placement of ctenophores as the earliest
      diverging extant multicellular animals. A single origin of spiral cleavage (with
      subsequent losses) is inferred from well-supported nodes. Many relationships
      between a stable subset of taxa find strong support, and a diminishing number of
      lineages remain recalcitrant to placement on the tree.

PMID- 18322465
TI  - Tracking the ends: a dynamic protein network controls the fate of microtubule
      tips.
AB  - Microtubule plus-end tracking proteins (+TIPs) are a diverse group of
      evolutionarily conserved cellular factors that accumulate at the ends of growing
      microtubules. They form dynamic networks through the interaction of a limited set
      of protein modules, repeat sequences and linear motifs that bind to each other
      with moderate affinities. +TIPs regulate different aspects of cell architecture
      by controlling microtubule dynamics, microtubule interactions with cellular
      structures and signalling factors, and the forces that are exerted on microtubule
      networks.

PMID- 18322466
TI  - Childhood of a phoenix: modern biology in Eastern and South-Eastern Europe.
AB  - With the expanding unification of Europe, the face of European science is
      changing. For some countries these changes are more pronounced than for others.
      Here, we survey the present state of science, most notably molecular biology
      research, in Eastern and South-Eastern European countries. We focus on the
      strategies these countries are taking in their quest for scientific excellence,
      discuss some of the acute challenges they face and explore several success
      stories in the making.

PMID- 18322467
TI  - Zonisamide prevents olanzapine-associated hyperphagia, weight gain, and elevated
      blood glucose in rats.
AB  - Olanzapine (OLZ), one of the second-generation atypical antipsychotics (SGAs),
      has shown relative advantages in patient adherence and outcomes. However, OLZ has
      also been associated with a higher incidence of weight gain than most other SGAs.
      Excessive weight gain may in turn contribute to long-term health concerns for
      some individuals. Zonisamide (ZNS), a medication approved in the United States as
      an adjunct in the management of epilepsy, has a diverse pharmacological profile,
      including sodium channel blockade, monoamine enhancement, and inhibition of
      carbonic anhydrase. ZNS has also been reported to cause weight loss in both
      humans and rodents. We hypothesized that this profile might be beneficial when co
      administered with OLZ. To test this hypothesis, we evaluated the effects of OLZ
      on body weight, as well as the pathways known to regulate feeding behavior and
      arousal in the Sprague-Dawley rat. As indicated via c-Fos expression, we found an
      OLZ-induced activation in the nucleus accumbens and orexin neurons in the lateral
      hypothalamus. An OLZ-associated development of hyperphagia, weight gain and
      elevated blood glucose in the rat was also found. These outcomes were attenuated
      and reversed in the presence of concomitant ZNS. These results suggest the
      hypothesis that ZNS may effectively treat or prevent weight gain or metabolic
      changes associated with the SGAs. Future studies of this combination in patients
      through appropriately designed human clinical studies are encouraged.

PMID- 18322468
TI  - Impact of ovarian hormones on the modulation of the serotonin transporter by
      fluvoxamine.
AB  - Most preclinical studies examining the mechanism(s) of action of antidepressants
      are carried out using male animals. Blockade of serotonin transporter (SERT)
      function by selective serotonin reuptake inhibitors (SSRIs) is the initial event
      that triggers a not completely understood process that results in clinical
      improvement in depression. To investigate whether there are differences in the
      ability of SSRIs to inhibit the SERT between male and female rats at different
      phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was
      measured by in vivo chronoamperometry. Local application of the SSRI,
      fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5
      HT clearance time parameters in male rats and female rats in estrus or diestrus,
      but not in proestrus. The contribution of ovarian steroids to this result was
      investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB)
      and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance
      time parameters, whereas EB and/or P treatment blocked this effect, consistent
      with what was seen in female rats in proestrus. This effect was gender-specific,
      since treatment of castrated rats with EB/P had no effect on the ability of
      fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed
      that 1-60 min after local application of 17-beta-estradiol (E(2)) into the CA3
      region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E(2)-BSA
      mimicked E(2)'s effects at 10 min but not at 60 min. Pretreatment with estrogen
      receptor antagonists blocked the effects of E(2). The finding that acutely both
      estradiol and progesterone can inhibit the ability of an SSRI to slow the
      clearance of 5-HT, may have important implications for the use of SSRIs in women.

PMID- 18322469
TI  - Long-interval cortical inhibition from the dorsolateral prefrontal cortex: a TMS
      EEG study.
AB  - Several studies have demonstrated that cortical inhibition (CI) can be recorded
      by paired transcranial magnetic stimulation (TMS) of the motor cortex and
      recorded by surface electromyography (EMG). However, recording CI from other
      cortical regions that are more closely associated with the pathophysiology of
      some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex
      (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was
      designed to investigate whether CI could be measured directly from the motor
      cortex and DLPFC by combining TMS with electroencephalography (EEG). Long
      interval CI (LICI) is a TMS paradigm that was used to index CI in the motor
      cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in
      significant suppression (32.8+/-30.5%) of mean cortical evoked activity on EEG,
      which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI
      resulted in significant suppression (30.1+/-26.9%) of mean cortical evoked
      activity and also correlated with LICI in the motor cortex. These data suggest
      that CI can be recorded by combining TMS with EEG and may facilitate future
      research attempting to ascertain the role of CI in the pathophysiology of several
      neurological and psychiatric disorders.

PMID- 18322470
TI  - Abnormal indices of cell cycle activity in schizophrenia and their potential
      association with oligodendrocytes.
AB  - The goal of this study was to determine what signaling pathways may elicit myelin
      specific gene expression deficits in schizophrenia (SZ). Microarray analyses
      indicated that genes associated with canonical cell cycle pathways were
      significantly affected in the anterior cingulate gyrus (ACG), the region
      exhibiting the most profound myelin-specific gene expression changes, in persons
      with SZ (N=16) as compared with controls (N=19). Detected gene expression changes
      of key regulators of G1/S phase transition and genes central to oligodendrocyte
      differentiation were validated using qPCR in the ACG in an independent cohort
      (Ns=45/34). The relative abundance of phosphorylated retinoblastoma protein (pRb)
      was increased in the white matter underlying the ACG in SZ subjects (Ns=12). The
      upregulation of cyclin D1 gene expression and the downregulation of p57(Kip2),
      accompanied by increased cyclin D/CDK4-dependent phosphorylation of pRb, acting
      as a checkpoint for G1/S phase transition, suggest abnormal cell cycle re-entry
      in postmitotic oligodendrocytes in SZ. Furthermore, gene expression profiling of
      brain samples from myelin mutant animal models, quaking and myelin-associated
      glycoprotein (MAG) null mice, showed that cell cycle gene expression changes were
      not a necessary consequence of the reduced gene expression of structural myelin
      proteins, such as MAG. While, quaking, a known modulator of cell cycle activity
      during oligodendrocyte differentiation impairs the expression of multiple myelin
      genes, including those that are affected in SZ. These data suggest that the
      normal patterns of cell cycle gene and protein expression are disrupted in SZ and
      that this disruption may contribute to the oligodendroglial deficits observed in
      SZ.

PMID- 18322472
TI  - Why should we increase public awareness of bladder cancer, and how can we do it?

PMID- 18322474
TI  - Arousal by stimulation of deep-brain nuclei.
AB  - Schiff et al. show that deep-brain stimulation of the unspecific thalamocortical
      system through certain midline thalamic nuclei produces an alerting effect in a
      patient in a minimally conscious state. Such nuclei include the central lateral
      nucleus, paralaminar regions of the median dorsalis, and the posterior-medial
      aspect of the centromedian/parafascicularis nucleus complex.

PMID- 18322478
TI  - Time to connect.

PMID- 18322479
TI  - No more scavenger hunts.

PMID- 18322480
TI  - The EPA's tailspin.

PMID- 18322483
TI  - Bright hopes pervade dark matter.

PMID- 18322484
TI  - Crunch time for peer review in lawsuit.

PMID- 18322485
TI  - Entomologists stifled by Indian bureaucracy.

PMID- 18322486
TI  - Save the trees.

PMID- 18322487
TI  - Magnets touted as fix for fusion reactor.

PMID- 18322489
TI  - Nobel prizewinner's paper retracted.

PMID- 18322497
TI  - The scientist delusion.

PMID- 18322498
TI  - Gravitational astronomy: hearing the heavens.

PMID- 18322499
TI  - Archaeology: facing up to the past.

PMID- 18322500
TI  - Oceanography: red tide rising.

PMID- 18322501
TI  - Tibet's seeds must be stored as climate changes.

PMID- 18322502
TI  - Double-blind review: let diversity reign.

PMID- 18322503
TI  - Double-blind review: easy to guess in specialist fields.

PMID- 18322504
TI  - Double-blind review: the paw print is a giveaway.

PMID- 18322505
TI  - Who stands to lose from double-blind review?

PMID- 18322506
TI  - Duplication: most cases on database are innocent.

PMID- 18322507
TI  - Duplication and plagiarism increasing among students.

PMID- 18322508
TI  - Duplication spreads the word to a wider audience.

PMID- 18322509
TI  - Duplication: stop favouring applicant with longest list.

PMID- 18322516
TI  - Physiology: Keeping it regular with protons.

PMID- 18322518
TI  - Quantum physics: tangled memories.

PMID- 18322519
TI  - Neuroscience: a complex in psychosis.

PMID- 18322520
TI  - Ageing: rushed decisions.

PMID- 18322521
TI  - Palaeontology: modern life in ancient mats.

PMID- 18322522
TI  - Magnetospheric physics: hiss from the chorus.

PMID- 18322523
TI  - Genomics: fungal symbiosis unearthed.

PMID- 18322524
TI  - Solid-state physics: how does your quasicrystal grow?

PMID- 18322525
TI  - Cyclical DNA methylation of a transcriptionally active promoter.
AB  - Processes that regulate gene transcription are directly under the influence of
      the genome organization. The epigenome contains additional information that is
      not brought by DNA sequence, and generates spatial and functional constraints
      that complement genetic instructions. DNA methylation on CpGs constitutes an
      epigenetic mark generally correlated with transcriptionally silent condensed
      chromatin. Replication of methylation patterns by DNA methyltransferases
      maintains genome stability through cell division. Here we present evidence of an
      unanticipated dynamic role for DNA methylation in gene regulation in human cells.
      Periodic, strand-specific methylation/demethylation occurs during transcriptional
      cycling of the pS2/TFF1 gene promoter on activation by oestrogens. DNA
      methyltransferases exhibit dual actions during these cycles, being involved in
      CpG methylation and active demethylation of 5mCpGs through deamination.
      Inhibition of this process precludes demethylation of the pS2 gene promoter and
      its subsequent transcriptional activation. Cyclical changes in the methylation
      status of promoter CpGs may thus represent a critical event in transcriptional
      achievement.

PMID- 18322526
TI  - The MC-Fold and MC-Sym pipeline infers RNA structure from sequence data.
AB  - The classical RNA secondary structure model considers A.U and G.C Watson-Crick as
      well as G.U wobble base pairs. Here we substitute it for a new one, in which sets
      of nucleotide cyclic motifs define RNA structures. This model allows us to unify
      all base pairing energetic contributions in an effective scoring function to
      tackle the problem of RNA folding. We show how pipelining two computer algorithms
      based on nucleotide cyclic motifs, MC-Fold and MC-Sym, reproduces a series of
      experimentally determined RNA three-dimensional structures from the sequence.
      This demonstrates how crucial the consideration of all base-pairing interactions
      is in filling the gap between sequence and structure. We use the pipeline to
      define rules of precursor microRNA folding in double helices, despite the
      presence of a number of presumed mismatches and bulges, and to propose a new
      model of the human immunodeficiency virus-1 -1 frame-shifting element.

PMID- 18322527
TI  - Structure and metal exchange in the cadmium carbonic anhydrase of marine diatoms.
AB  - Carbonic anhydrase, a zinc enzyme found in organisms from all kingdoms, catalyses
      the reversible hydration of carbon dioxide and is used for inorganic carbon
      acquisition by phytoplankton. In the oceans, where zinc is nearly depleted,
      diatoms use cadmium as a catalytic metal atom in cadmium carbonic anhydrase
      (CDCA). Here we report the crystal structures of CDCA in four distinct forms:
      cadmium-bound, zinc-bound, metal-free and acetate-bound. Despite lack of sequence
      homology, CDCA is a structural mimic of a functional beta-carbonic anhydrase
      dimer, with striking similarity in the spatial organization of the active site
      residues. CDCA readily exchanges cadmium and zinc at its active site--an
      apparently unique adaptation to oceanic life that is explained by a stable
      opening of the metal coordinating site in the absence of metal. Given the central
      role of diatoms in exporting carbon to the deep sea, their use of cadmium in an
      enzyme critical for carbon acquisition establishes a remarkable link between the
      global cycles of cadmium and carbon.

PMID- 18322528
TI  - The unexpected origin of plasmaspheric hiss from discrete chorus emissions.
AB  - Plasmaspheric hiss is a type of electromagnetic wave found ubiquitously in the
      dense plasma region that encircles the Earth, known as the plasmasphere. This
      important wave is known to remove the high-energy electrons that are trapped
      along the Earth's magnetic field lines, and therefore helps to reduce the
      radiation hazards to satellites and humans in space. Numerous theories to explain
      the origin of hiss have been proposed over the past four decades, but none have
      been able to account fully for its observed properties. Here we show that a
      different wave type called chorus, previously thought to be unrelated to hiss,
      can propagate into the plasmasphere from tens of thousands of kilometres away,
      and evolve into hiss. Our new model naturally accounts for the observed frequency
      band of hiss, its incoherent nature, its day-night asymmetry in intensity, its
      association with solar activity and its spatial distribution. The connection
      between chorus and hiss is very interesting because chorus is instrumental in the
      formation of high-energy electrons outside the plasmasphere, whereas hiss
      depletes these electrons at lower equatorial altitudes.

PMID- 18322529
TI  - Mapping photonic entanglement into and out of a quantum memory.
AB  - Developments in quantum information science rely critically on entanglement-a
      fundamental aspect of quantum mechanics that causes parts of a composite system
      to show correlations stronger than can be explained classically. In particular,
      scalable quantum networks require the capability to create, store and distribute
      entanglement among distant matter nodes by means of photonic channels. Atomic
      ensembles can play the role of such nodes. So far, in the photon-counting regime,
      heralded entanglement between atomic ensembles has been successfully demonstrated
      through probabilistic protocols. But an inherent drawback of this approach is the
      compromise between the amount of entanglement and its preparation probability,
      leading to intrinsically low count rates for high entanglement. Here we report a
      protocol where entanglement between two atomic ensembles is created by coherent
      mapping of an entangled state of light. By splitting a single photon and
      performing subsequent state transfer, we separate the generation of entanglement
      and its storage. After a programmable delay, the stored entanglement is mapped
      back into photonic modes with overall efficiency of 17%. Together with
      improvements in single-photon sources, our protocol will allow 'on-demand'
      entanglement of atomic ensembles, a powerful resource for quantum information
      science.

PMID- 18322530
TI  - Strong dispersive coupling of a high-finesse cavity to a micromechanical
      membrane.
AB  - Macroscopic mechanical objects and electromagnetic degrees of freedom can couple
      to each other through radiation pressure. Optomechanical systems in which this
      coupling is sufficiently strong are predicted to show quantum effects and are a
      topic of considerable interest. Devices in this regime would offer new types of
      control over the quantum state of both light and matter, and would provide a new
      arena in which to explore the boundary between quantum and classical physics.
      Experiments so far have achieved sufficient optomechanical coupling to laser-cool
      mechanical devices, but have not yet reached the quantum regime. The outstanding
      technical challenge in this field is integrating sensitive micromechanical
      elements (which must be small, light and flexible) into high-finesse cavities
      (which are typically rigid and massive) without compromising the mechanical or
      optical properties of either. A second, and more fundamental, challenge is to
      read out the mechanical element's energy eigenstate. Displacement measurements
      (no matter how sensitive) cannot determine an oscillator's energy eigenstate, and
      measurements coupling to quantities other than displacement have been difficult
      to realize in practice. Here we present an optomechanical system that has the
      potential to resolve both of these challenges. We demonstrate a cavity which is
      detuned by the motion of a 50-nm-thick dielectric membrane placed between two
      macroscopic, rigid, high-finesse mirrors. This approach segregates optical and
      mechanical functionality to physically distinct structures and avoids
      compromising either. It also allows for direct measurement of the square of the
      membrane's displacement, and thus in principle the membrane's energy eigenstate.
      We estimate that it should be practical to use this scheme to observe quantum
      jumps of a mechanical system, an important goal in the field of quantum
      measurement.

PMID- 18322531
TI  - Multi-membrane hydrogels.
AB  - Polysaccharide-based hydrogels are useful for numerous applications, from food
      and cosmetic processing to drug delivery and tissue engineering. The formation of
      hydrogels from polyelectrolyte solutions is complex, involving a variety of
      molecular interactions. The physical gelation of polysaccharides can be achieved
      by balancing solvophobic and solvophilic interactions. Polymer chain
      reorganization can be obtained by solvent exchange, one of the processing routes
      forming a simple hydrogel assembly. Nevertheless, many studies on hydrogel
      formation are empirical with a limited understanding of the mechanisms involved,
      delaying the processing of more complex structures. Here we use a multi-step
      interrupted gelation process in controlled physico-chemical conditions to
      generate complex hydrogels with multi-membrane 'onion-like' architectures. Our
      approach greatly simplifies the processing of gels with complex shapes and a
      multi-membrane organization. In contrast with existing assemblies described in
      the literature, our method allows the formation of free 'inter-membrane' spaces
      well suited for cell or drug introduction. These architectures, potentially
      useful in biomedical applications, open interesting perspectives by taking
      advantage of tailor-made three-dimensional multi-membrane tubular or spherical
      structures.

PMID- 18322532
TI  - Near-isothermal conditions in the middle and lower crust induced by melt
      migration.
AB  - The thermal structure of the crust strongly influences deformation, metamorphism
      and plutonism. Models for the geothermal gradient in stable crust predict a
      steady increase of temperature with depth. This thermal structure, however, is
      incompatible with observations from high-temperature metamorphic terranes exhumed
      in orogens. Global compilations of peak conditions in high-temperature
      metamorphic terranes define relatively narrow ranges of peak temperatures over a
      wide range in pressure, for both isothermal decompression and isobaric cooling
      paths. Here we develop simple one-dimensional thermal models that include the
      effects of melt migration. These models show that long-lived plutonism results in
      a quasi-steady-state geotherm with a rapid temperature increase in the upper
      crust and nearly isothermal conditions in the middle and lower crust. The models
      also predict that the upward advection of heat by melt generates granulite facies
      metamorphism, and widespread andalusite-sillimanite metamorphism in the upper
      crust. Once the quasi-steady-state thermal profile is reached, the middle and
      lower crust are greatly weakened due to high temperatures and anatectic
      conditions, thus setting the stage for gravitational collapse, exhumation and
      isothermal decompression after the onset of plutonism. Near-isothermal conditions
      in the middle and lower crust result from the thermal buffering effect of
      dehydration melting reactions that, in part, control the shape of the geotherm.

PMID- 18322533
TI  - High-amplitude fluctuations and alternative dynamical states of midges in Lake
      Myvatn.
AB  - Complex dynamics are often shown by simple ecological models and have been
      clearly demonstrated in laboratory and natural systems. Yet many classes of
      theoretically possible dynamics are still poorly documented in nature. Here we
      study long-term time-series data of a midge, Tanytarsus gracilentus (Diptera:
      Chironomidae), in Lake Myvatn, Iceland. The midge undergoes density fluctuations
      of almost six orders of magnitude. Rather than regular cycles, however, these
      fluctuations have irregular periods of 4-7 years, indicating complex dynamics. We
      fit three consumer-resource models capable of qualitatively distinct dynamics to
      the data. Of these, the best-fitting model shows alternative dynamical states in
      the absence of environmental variability; depending on the initial midge
      densities, the model shows either fluctuations around a fixed point or high
      amplitude cycles. This explains the observed complex population dynamics: high
      amplitude but irregular fluctuations occur because stochastic variability causes
      the dynamics to switch between domains of attraction to the alternative states.
      In the model, the amplitude of fluctuations depends strongly on minute resource
      subsidies into the midge habitat. These resource subsidies may be sensitive to
      human-caused changes in the hydrology of the lake, with human impacts such as
      dredging leading to higher-amplitude fluctuations. Tanytarsus gracilentus is a
      key component of the Myvatn ecosystem, representing two-thirds of the secondary
      productivity of the lake and providing vital food resources to fish and to
      breeding bird populations. Therefore the high-amplitude, irregular fluctuations
      in midge densities generated by alternative dynamical states dominate much of the
      ecology of the lake.

PMID- 18322534
TI  - The genome of Laccaria bicolor provides insights into mycorrhizal symbiosis.
AB  - Mycorrhizal symbioses--the union of roots and soil fungi--are universal in
      terrestrial ecosystems and may have been fundamental to land colonization by
      plants. Boreal, temperate and montane forests all depend on ectomycorrhizae.
      Identification of the primary factors that regulate symbiotic development and
      metabolic activity will therefore open the door to understanding the role of
      ectomycorrhizae in plant development and physiology, allowing the full ecological
      significance of this symbiosis to be explored. Here we report the genome sequence
      of the ectomycorrhizal basidiomycete Laccaria bicolor (Fig. 1) and highlight gene
      sets involved in rhizosphere colonization and symbiosis. This 65-megabase genome
      assembly contains approximately 20,000 predicted protein-encoding genes and a
      very large number of transposons and repeated sequences. We detected unexpected
      genomic features, most notably a battery of effector-type small secreted proteins
      (SSPs) with unknown function, several of which are only expressed in symbiotic
      tissues. The most highly expressed SSP accumulates in the proliferating hyphae
      colonizing the host root. The ectomycorrhizae-specific SSPs probably have a
      decisive role in the establishment of the symbiosis. The unexpected observation
      that the genome of L. bicolor lacks carbohydrate-active enzymes involved in
      degradation of plant cell walls, but maintains the ability to degrade non-plant
      cell wall polysaccharides, reveals the dual saprotrophic and biotrophic lifestyle
      of the mycorrhizal fungus that enables it to grow within both soil and living
      plant roots. The predicted gene inventory of the L. bicolor genome, therefore,
      points to previously unknown mechanisms of symbiosis operating in biotrophic
      mycorrhizal fungi. The availability of this genome provides an unparalleled
      opportunity to develop a deeper understanding of the processes by which symbionts
      interact with plants within their ecosystem to perform vital functions in the
      carbon and nitrogen cycles that are fundamental to sustainable plant
      productivity.

PMID- 18322535
TI  - Transient cyclical methylation of promoter DNA.
AB  - Methylation of CpG dinucleotides is generally associated with epigenetic
      silencing of transcription and is maintained through cellular division. Multiple
      CpG sequences are rare in mammalian genomes, but frequently occur at the
      transcriptional start site of active genes, with most clusters of CpGs being
      hypomethylated. We reported previously that the proximal region of the trefoil
      factor 1 (TFF1, also known as pS2) and oestrogen receptor alpha (ERalpha)
      promoters could be partially methylated by treatment with deacetylase inhibitors,
      suggesting the possibility of dynamic changes in DNA methylation. Here we show
      that cyclical methylation and demethylation of CpG dinucleotides, with a
      periodicity of around 100 min, is characteristic for five selected promoters,
      including the oestrogen (E2)-responsive pS2 gene, in human cells. When the pS2
      gene is actively transcribed, DNA methylation occurs after the cyclical occupancy
      of ERalpha and RNA polymerase II (polII). Moreover, we report conditions that
      provoke methylation cycling of the pS2 promoter in cell lines in which pS2
      expression is quiescent and the proximal promoter is methylated. This coincides
      with a low-level re-expression of ERalpha and of pS2 transcripts.

PMID- 18322536
TI  - Genetic tracing reveals a stereotyped sensory map in the olfactory cortex.

PMID- 18322539
TI  - A young man with Propionibacterium acnes-induced shunt nephritis.

PMID- 18322540
TI  - The zebrafish pronephros: a model to study nephron segmentation.
AB  - Nephrons possess a segmental organization where each segment is specialized for
      the secretion and reabsorption of particular solutes. The developmental control
      of nephron segment patterning remains one of the enigmas within the field of
      renal biology. Achieving an understanding of the mechanisms that direct nephron
      segmentation has the potential to shed light on the causes of kidney birth
      defects and renal diseases in humans. Researchers studying embryonic kidney
      development in zebrafish and Xenopus have recently demonstrated that the
      pronephric nephrons in these vertebrates are segmented in a similar fashion as
      their mammalian counterparts. Further, it has been shown that retinoic acid
      signaling establishes proximodistal segment identities in the zebrafish
      pronephros by modulating the expression of renal transcription factors and
      components of signaling pathways that are known to direct segment fates during
      mammalian nephrogenesis. These findings present the zebrafish model as an
      excellent genetic system in which to interrogate the conserved developmental
      pathways that control nephron segmentation in both lower vertebrates and mammals.

PMID- 18322541
TI  - Renal risk scores: progress and prospects.
AB  - Worldwide adoption of the Kidney Disease Outcomes Quality Initiative
      classification for chronic kidney disease (CKD) and widespread use of the
      estimated glomerular filtration rate to assess renal function have identified
      large numbers of patients with previously undiagnosed CKD. It is clear, however,
      that this is a heterogeneous group and that only a small minority of such
      patients ever progress to end-stage renal disease. There is thus an urgent need
      for a simple method of risk assessment that can be applied to all patients with
      CKD to identify those few at greatest risk. The magnitude of baseline proteinuria
      has long been recognized as an important predictor of renal prognosis.
      Furthermore, several studies have found that change in proteinuria after
      initiation of antihypertensive treatment as well as achieved level of proteinuria
      correlate with prognosis. Thus, proteinuria has emerged as the single most
      important marker of renal risk. Many other factors have been identified as risk
      factors for CKD progression. Several attempts have been made to combine a
      relatively small number of risk factors into a risk score to predict renal
      outcomes in specific groups of patients. Validation of these risk scores as well
      as further studies are now required to develop a renal risk score applicable to a
      more general population of patients with CKD. Similar methodology could be
      applied to assess the important issue of the cardiovascular risk associated with
      CKD.

PMID- 18322543
TI  - Pathways of fluid transport and reabsorption across the peritoneal membrane.
AB  - The three-pore model of peritoneal fluid transport predicts that once the osmotic
      gradient has dissipated, fluid reabsorption will be due to a combination of small
      pore reabsorption driven by the intravascular oncotic pressure, and an underlying
      disappearance of fluid from the cavity by lymphatic drainage. Our study measured
      fluid transport by these pathways in the presence and absence of an osmotic
      gradient. Paired hypertonic and standard glucose-dwell studies were performed
      using radio-iodinated serum albumin as an intraperitoneal volume marker and
      changes in intraperitoneal sodium mass to determine small-pore versus
      transcellular fluid transport. Disappearance of iodinated albumin was considered
      to indicate lymphatic drainage. Variability in transcellular ultrafiltration was
      largely explained by the rate of small-solute transport across the membrane. In
      the absence of an osmotic gradient, fluid reabsorption occurred via the small
      pore pathway, the rate being proportional to the small-solute transport
      characteristics of the membrane. In most cases, fluid removal from the peritoneal
      cavity by this pathway was faster than by lymphatic drainage. Our study shows
      that the three-pore model describes the pathways of peritoneal fluid transport
      well. In the presence of high solute transport, poor transcellular
      ultrafiltration was due to loss of the osmotic gradient and an enhanced small
      pore reabsorption rate after this gradient dissipated.

PMID- 18322542
TI  - Sphingosine-1-phosphate receptors: biology and therapeutic potential in kidney
      disease.
AB  - The major sphingolipid metabolite, sphingosine-1-phosphate (S1P), has important
      biological functions. S1P is the ligand for a family of five G-protein-coupled
      receptors with distinct signaling pathways that regulate angiogenesis, vascular
      maturation, immunity, chemotaxis, and other important biological pathways.
      Recently, clinical trials have targeted S1P receptors (S1PRs) for autoimmune
      diseases and transplantation and have generated considerable interest in
      developing additional, more selective compounds. This review summarizes current
      knowledge on the biology of S1P and S1PRs that forms the basis for future drug
      development and the treatment of kidney disease.

PMID- 18322544
TI  - Paroxysmal hypertension due to baroreflex failure.

PMID- 18322545
TI  - A novel renal carbonic anhydrase type III plays a role in proximal tubule
      dysfunction.
AB  - Dysfunction of the proximal tubule (PT) is associated with variable degrees of
      solute wasting and low-molecular-weight proteinuria. We measured metabolic
      consequences and adaptation mechanisms in a model of inherited PT disorders using
      PT cells of ClC-5-deficient (Clcn5Y/-) mice, a well-established model of Dent's
      disease. Compared to cells taken from control mice, those from the mutant mice
      had increased expression of markers of proliferation (Ki67, proliferative cell
      nuclear antigen (PCNA), and cyclin E) and oxidative scavengers (superoxide
      dismutase I and thioredoxin). Transcriptome and protein analyses showed fourfold
      induction of type III carbonic anhydrase in a kidney-specific manner in the
      knockout mice located in scattered PT cells. Kidney-specific carbonic anhydrase
      type III (CAIII) upregulation was confirmed in other mice lacking the multiligand
      receptor megalin and in a patient with Dent's disease due to an inactivating
      CLCN5 mutation. The type III enzyme was specifically detected in the urine of
      mice lacking ClC-5 or megalin, patients with Dent's disease, and in PT cell lines
      exposed to oxidative stress. Our study shows that lack of PT ClC-5 in mice and
      men is associated with CAIII induction, increased cell proliferation, and
      oxidative stress.

PMID- 18322546
TI  - B-cell O-galactosyltransferase activity, and expression of O-glycosylation genes
      in bone marrow in IgA nephropathy.
AB  - In IgA nephropathy (IgAN), pathogenic IgA1 is likely derived from bone marrow
      (BM) cells and exhibits reduced O-galactosylation. Defective O-galactosylation
      may arise from the compromised expression or function of the enzyme beta
      galactosyltransferase and/or its molecular chaperone (Cosmc). We measured B-cell
      O-galactosylation activity and the relative gene expression of beta
      galactosyltransferase and Cosmc in peripheral blood and BM taken from patients
      with IgAN and controls. O-galactosylation activity was measured in peripheral and
      BM B cells by the incorporation of radiolabeled galactose into an asialo-mucin
      acceptor. Gene expression of beta-galactosyltransferase and Cosmc was measured by
      real-time PCR and related to that of the enzyme GalNAc-T2 (UDP-N-acetyl-alpha-D
      galactosamine:polypeptide N-acetylgalactosaminyltransferase-2), which synthesizes
      the core O-glycan. Neither the B-cell O-galactosylation activity nor the gene
      expression of the enzyme or chaperone was different between patients and
      controls. However, the relationships between the O-glycosylation of serum IgA1,
      galactosylation activity, and beta-galactosyltransferase gene expression showed
      different patterns in IgAN and controls. In IgAN, O-galactosylation activity
      correlated with beta-galactosyltransferase gene expression, but not with IgA1 O
      glycosylation, suggesting that factors other than the availability of beta
      galactosyltransferase or Cosmc are responsible for altered IgA1 O-glycosylation.

PMID- 18322547
TI  - Short- and long-term discontinuation patterns of commonly prescribed
      antihypertensive drugs among a Chinese population: cohort study.
AB  - This retrospective cohort study compared cumulative incidences of
      antihypertensive drug discontinuation at 8 and 48 weeks in two public primary
      care clinics in Hong Kong, including 2531 patients who newly received a first
      ever antihypertensive monotherapy during the period 1990-2002. from clinical
      patient records, thiazide diuretics had significantly lower discontinuation rates
      (0.00%) as compared to all other drug classes at 8 weeks in both young males (
      range: 5.4-10.8% in other classes, P <0.001), while at 48 weeks calcium channel
      blockers (CCBs) showed the highest discontinuation rate (23.0%, 955 CI 17.0%,
      29.0%) significantly different from beta-blockers (14.4%, 95% CI 10.9%, 17.9%,
      P=0.011) and thiazide diuretics ( 13.1 %, 95% CI 8.6%, 17.6%, P=0.010) in young
      females ( overall P= 0.041). This finding highlights cautions of higher rates of
      discontinuing CCBs in the long term, and the lower short-term discontinuation
      rates of thiazides than other drug classes, which strengthens the recommendations
      from international authorities such as the British Hypertension Society as a best
      first-line drug for Chinese patients.

PMID- 18322548
TI  - Tetrahydrobiopterin: a novel antihypertensive therapy.
AB  - Tetrahydrobiopterin (BH(4)) is a cofactor for the nitric oxide (NO) synthase
      enzymes, such that its insufficiency results in uncoupling of the enzyme, leading
      to release of superoxide rather than NO in disease states, including
      hypertension. We hypothesized that oral BH(4) will reduce arterial blood pressure
      (BP) and improve endothelial function in hypertensive subjects. Oral BH(4) was
      given to subjects with poorly controlled hypertension (BP >135/85 mm Hg) and
      weekly measurements of BP and endothelial function made. In Study 1, 5 or 10 mg
      kg(-1) day(-1) of BH(4) (n=8) was administered orally for 8 weeks, and in Study
      2, 200 and 400 mg of BH(4) (n=16) was given in divided doses for 4 weeks. Study
      1: significant reductions in systolic (P=0.005) and mean BP (P=0.01) were
      observed with both doses of BH(4). Systolic BP was 15+/-15 mm Hg (P=0.04) lower
      after 5 weeks and persisted for the 8-week study period. Study 2: subjects given
      400 mg BH(4) had decreased systolic (P=0.03) and mean BP (P=0.04), with a peak
      decline of 16+/-19 mm Hg (P=0.04) at 3 weeks. BP returned to baseline 4 weeks
      after discontinuation. Significant improvement in endothelial function was
      observed in Study 1 subjects and those receiving 400 mg BH(4). There was no
      significant change in subjects given the 200 mg dose. This pilot investigation
      indicates that oral BH(4) at a daily dose of 400 mg or higher has a significant
      and sustained antihypertensive effect in subjects with poorly controlled
      hypertension, an effect that is associated with improved endothelial NO
      bioavailability.

PMID- 18322549
TI  - Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic
      encephalopathy.
AB  - BACKGROUND: Iron delocalization or misregulation of iron metabolism may play a
      critical role in the pathology of hypoxic ischemic encephalopathy (HIE).
      OBJECTIVE: To study iron metabolism and lipid peroxidation in newborn infants and
      to correlate non-protein-bound iron (NPBI) concentration with the severity of the
      post-asphyxial injury and subsequent short-term outcomes. STUDY DESIGN:
      Concentrations of NPBI and malondialdehyde (MDA) in the serum and in the
      cerebrospinal fluid (CSF) were measured in eight healthy newborn infants and nine
      newborn infants suffering from moderately severe HIE. Short-term outcomes (death,
      survival with or without neurological abnormality) were noted at hospital
      discharge. RESULT: Serum and CSF concentrations of both NPBI and MDA were
      significantly increased in HIE infants when compared to controls. Serum iron was
      significantly increased and total iron binding capacity was significantly
      decreased in HIE infants compared to controls. Out of the nine HIE infants, four
      infants died and two infants survived with abnormal neurological findings at
      hospital discharge. These six infants with clinical sequels had significantly
      increased concentrations of NPBI in the serum and in the CSF; and increased
      concentrations of MDA in the CSF when compared to the other three who survived
      without short-term abnormalities. CONCLUSION: We conclude that hypoxia ischemia
      alters iron metabolism and lipid peroxidation in newborn infants; and that NPBI
      and MDA in the CSF are increased in infants with HIE. This study supports a role
      for iron in oxidative injury to the central nervous system after hypoxic ischemic
      insults.

PMID- 18322550
TI  - Cardiac troponin T and N-terminal-pro-B type natriuretic peptide reflect
      myocardial function in preterm infants.
AB  - BACKGROUND: Cardiovascular compromise is increasingly recognized in preterm
      infants. Currently, echocardiography is the best tool to assess myocardial
      contractility and guide management. Elevated levels of cardiac troponin T (cTnT)
      and N-terminal-pro-B type natriuretic peptide (NTpBNP) are associated with poor
      myocardial contractility and low cardiac output in adults. OBJECTIVE: To examine
      the range of cTnT and NTpBNP in preterm infants, to correlate NTpBNP and cTnT
      with echocardiographic markers of cardiac function and to assess the influence of
      antenatal and postnatal factors on these biochemical markers. STUDY DESIGN:
      Plasma concentrations of cTnT and NTpBNP were measured in infants <1500 g at 12 h
      of age. These were correlated with simultaneous echocardiographic measures of
      myocardial function and output. Antenatal data, infant demographics and postnatal
      characteristics were prospectively recorded. RESULT: A total of 80 infant had
      samples taken and echocardiography performed. Their median (interquartile range)
      cTnT and NTpBNP values were 0.20 microg l(-1) (0.11 to 0.40) and 1273 pmol l(-1)
      (664 to 2798), respectively. There was a significant inverse correlation between
      cTnT and echocardiographic markers of myocardial function and stroke volume.
      NTpBNP significantly correlated with left atrial to aortic root ratio (LA:Ao).
      There was a weaker but significant negative correlation between NTpBNP and left
      ventricular (LV) function. The assays were not influenced by gestation, birth
      weight, gender or mode of delivery. CONCLUSION: cTnT and NTpBNP are correlated
      with echocardiographic measures of cardiac performance in preterm infants.
      Measurement of levels in the first hours of life may provide useful information
      regarding myocardial function and volume loading.

PMID- 18322551
TI  - Israel guidelines for the management of neonatal hyperbilirubinemia and
      prevention of kernicterus.
AB  - Despite publication of guidelines for the prevention and management of
      hyperbilirubinemia in term and late-preterm newborn infants, kernicterus,
      although rare, continues to occur. Guidelines written for use in one country may
      not always be universally appropriate. Bearing this in mind, a committee
      appointed by the Israel Neonatal Society has formulated a set of guidelines,
      based on those of the American Academy of Pediatrics (2004), but adapted to the
      realities of the Israeli scene. The guidelines include methods of surveillance of
      jaundice, prediction of jaundice, assessment of risk factors, discharge planning
      and post-discharge follow-up, in addition to therapeutic guidelines including
      indications for phototherapy, exchange transfusion and the use of intravenous
      immune globulin. Availability of these guidelines to the international community
      may offer direction to physicians of other countries who may be setting up
      guidelines for use in their own communities.

PMID- 18322552
TI  - Impact of early infant feeding practices on mortality in low birth weight infants
      from rural Ghana.
AB  - OBJECTIVE: To assess the impact of early infant feeding practices on low birth
      weight- (LBW) specific neonatal mortality in rural Ghana. STUDY DESIGN: A total
      of 11 787-breastfed babies were born between July 2003 and June 2004 and survived
      to day 2. Overall, 3411 (30.3%) infants had weight recorded within 48 h. Two
      hundred and ninety-six (8.7%) infants were <2.5 kg and 15 died in the neonatal
      period. Associations were examined using multivariate logistic regression.
      RESULT: Initiation of breastfeeding after day 1 was associated with a threefold
      increase in mortality risk (adjusted odds ratio (adjOR) 3.23, 95% confidence
      interval (95% CI) (1.07-9.82)) in infants aged 2 to 28 days. Prelacteal feeding
      was associated with a threefold significantly increased mortality risk (adjOR
      3.12, 95% CI (1.19-8.22)) in infants aged 2 to 28 days but there was no
      statistically significant increase in risk associated with predominant
      breastfeeding (adjOR 1.91, 95% CI (0.60-6.09)). There were no modifications of
      these effects by birth weight. The sample size was insufficient to allow
      assessment of the impact of partial breastfeeding. CONCLUSION: Improving early
      infant feeding practices is an effective, feasible, low-cost intervention that
      could reduce early infant mortality in LBW infants in developing countries. These
      findings are especially relevant for sub-Saharan Africa where many LBW infants
      are born at home, never taken to a health facility and mortality rates are
      unacceptably high.

PMID- 18322553
TI  - Efficacy, immune responses and side-effects of vaccines against Johne's disease
      in young red deer (Cervus elaphus) experimentally challenged with Mycobacterium
      avium subsp paratuberculosis.
AB  - AIMS: To test the efficacy of a commercially available and an experimental
      vaccine against Johne's disease in young red deer (Cervus elaphus), using
      experimental challenge with live virulent Mycobacterium avium subsp
      paratuberculosis (M. ptb), measure injection-site reactions, and assess the
      effects of vaccination and challenge on results of subsequent skin tests and
      ancillary blood tests for bovine tuberculosis (Tb). METHODS: Ninety 6-8-week-old
      red deer fawns were randomly allocated to three equal groups of 30, and received
      either a 1-ml S/C injection of either a commercially available whole-cell killed
      vaccine with a mineral-oil adjuvant (COM), or a live attenuated M. ptb
      experimental vaccine with a lipid adjuvant (EXP), or were unvaccinated controls.
      Ten weeks later (Week 10), all 90 fawns received an oral challenge with
      approximately 10(8) cfu of a bovine strain of M. ptb daily for 4 days. The fawns
      were regularly weighed and monitored for clinical signs of Johne's disease, and
      regularly blood-sampled and tested for antibodies to M. ptb, using the Paralisa
      test, an IgG1 ELISA, and for antibodies to Mycobacterium bovis, using a similar
      test. A mid-cervical tuberculin skin test (MCT) was administered at Week 23, and
      comparative cervical skin tests (CCTs) were administered at Weeks 37 and 57. All
      animals were electively killed at Week 59, injection sites inspected,
      gastrointestinal tracts examined for gross lesions, and samples taken for culture
      and histopathology. RESULTS: There were no clinical cases of Johne's disease but,
      at slaughter, more gross lesions in intestinal lymph nodes were observed in
      Control (20%) than COM animals (0%; p<0.05). This latter group also had less
      severe histopathological lesions in samples of intestines and lymph nodes
      compared with the Control group (p<0.05), but not deer in the EXP group. Over 89%
      of deer in all three groups were shown by culture to be infected with M. ptb,
      while only 21-33% of faecal samples were culture-positive. Time to positive
      culture was longer for COM vs EXP and Control groups (p<0.01), reflecting fewer
      M. ptb organisms in samples from the ileocaecal valve (ICV) in that group. Almost
      all (>or=90%) deer reacted to the MCT at Week 23, and there were no significant
      differences between groups. One or two deer in each group were classified as Tb
      reactors to the CCT at Week 37, and none were classified as Tb reactors to the
      CCT at Week 57. At the time of challenge, over 50% of deer in the COM group were
      classified as positive (9/28) or suspicious (7/28) for M. ptb antibodies in the
      Paralisa test, one animal in the EXP group was classified as suspicious, and all
      the Controls were negative. From Week 23 to the end of the trial, 25/28 (89%)
      deer in the COM group were Paralisa-positive or -suspicious. The proportion of
      animals in the EXP and Control groups that were Paralisa-positive peaked at Week
      39 (60% and 55%, respectively). The majority of deer in the COM group had
      significant levels of antibody to M. bovis 10 weeks after vaccination, while the
      proportion of M. bovis-antibody positive Control deer rose gradually throughout
      the trial, reaching 23/30 (77%) at slaughter. Injection-site lesions in COM deer
      ranged from 10-38 mm in diameter 4 weeks after vaccination, and then resolved.
      Minimal injection-site lesions were observed in EXP deer. At slaughter, 14 months
      after vaccination, 19/28 deer in the COM group had 5-15-mm nodules that were
      easily trimmed from the carcass. CONCLUSIONS: The experimental challenge with M.
      ptb produced subclinical Johne's disease in the majority of deer, but did not
      cause any clinical disease. The number and severity of gross and microscopic
      lesions was significantly reduced in the COM compared with Control and EXP
      groups; vaccination of the EXP group did not appear to give significant
      protection. Deer vaccinated with the commercial vaccine are likely to give a
      false-positive reaction to the MCT but should have an avian reaction to the CCT,
      if it is carried out >12 months after vaccination. Most of the deer vaccinated
      with the commercial vaccine produced significant levels of antibodies against
      both M. ptb and M. bovis, which interfered with ancillary Tb tests. If this
      vaccine or similar oil-based vaccines are used on deer farms in the future, it
      may be advisable to only vaccinate animals destined for slaughter, that would not
      need to be Tb-tested, but would be 'works-monitored' for evidence of Tb instead.

PMID- 18322554
TI  - Infection trials in pigs with a human isolate of Brucella ( isolate 02/611
      'marine mammal type' ).
AB  - AIM: To determine if pigs could support infection of a human Brucella isolate
      (Brucella 02/611) from New Zealand, and to study seroconversion to this isolate
      using a competitive ELISA. METHODS: Ten weaner piglets were challenged with 4.8 x
      10(8) cfu of organisms by the oral and ocular routes. Culture was attempted on
      blood samples taken prior to challenge, and 4, 7, 9, 11, 14, 21 and 28 days post
      challenge, and on tissue samples taken at the termination of the trial, 1 month
      after challenge. Sera were analysed for antibody using an ELISA. For reference
      comparison, similar trials were conducted in two pigs using an isolate of
      Brucella suis biovar 1, and two pigs using an isolate of B. suis biovar 3.
      RESULTS: Brucella 02/611 organisms were re-isolated from one lymph node each from
      three pigs; all other samples were negative. Low and transient antibody titres
      were detected using a competitive ELISA in three pigs, two of which were culture
      negative. Organisms of B. suis reference strains were re-isolated from multiple
      samples from each of the four animals. CONCLUSION: Brucella 02/611 does not seem
      to replicate readily in pigs. It is unlikely that pigs were the original
      maintenance hosts for Brucella 02/611.

PMID- 18322555
TI  - Prevalence of Giardia and Cryptosporidium spp in calves from a region in New
      Zealand experiencing intensification of dairying.
AB  - AIM: To investigate the prevalence of Giardia and Cryptosporidium spp in calves
      born during two spring-calving seasons in a rapidly intensifying dairying region
      in the South Island; to evaluate potential correlations between the prevalence of
      the organism and age, characteristics of faeces, and animal-housing practices;
      and to compare the results with those from established dairying regions in the
      North Island. METHODS: A longitudinal study was conducted in 2005 and 2006 on 10
      dairy farms located in the Otago region, South Island, New Zealand. A total of
      1,190 faecal samples were collected from calves 1-7 weeks old. Direct
      immunofluorescent microscopy was used to screen the faecal samples for Giardia
      cysts and Cryptosporidium oocysts. The prevalence of Giardia and Cryptosporidium
      spp detected in calves in Otago was compared with that previously measured in
      calves from dairying regions in the Waikato and Manawatu, in the North Island .
      RESULTS: On average, Giardia and Cryptosporidium spp were detected in 31% and
      2.6% of all samples, respectively. The prevalence of Giardia spp cysts in faeces
      was higher in calves >or=3 weeks of age in 2005 (p<or=0.02) and in calves >or=2
      weeks of age in 2006 (p=0.07) than in younger calves. No age-related pattern was
      observed for Cryptosporidium spp in either year. No correlations were evident
      between characteristics of faeces or animal housing practices and the prevalence
      of either organism, which did not differ between the two dairy farming regions.
      CONCLUSIONS: Prevalence rates of Giardia and Cryptosporidium spp in calves 1-7
      weeks old did not differ between the two geographical regions, nor did the
      regions' distinct climate conditions appear to influence the prevalence of either
      pathogen. Considering data from both years together, the presence of Giardia spp
      cysts in faeces appeared to increase in the first week or two after birth, so
      that, on average, 30-40% of animals from 3-6 weeks of age were affected. CLINICAL
      RELEVANCE: This is the first study to report the prevalence of Giardia and
      Cryptosporidium spp in dairy calves in the South Island of New Zealand.

PMID- 18322556
TI  - Animal abuse and family violence: survey on the recognition of animal abuse by
      veterinarians in New Zealand and their understanding of the correlation between
      animal abuse and human violence.
AB  - AIMS: To establish the incidence, frequency and type of deliberate animal abuse
      seen in veterinary practice in New Zealand, and ascertain veterinarians'
      knowledge of human abuse within the families where animal abuse was occurring. To
      explore attitudes of veterinarians to and knowledge about the correlation between
      animal abuse and human violence, and their perceived role in dealing with such
      issues. METHODS: A postal questionnaire was sent to practising veterinarians in
      New Zealand. It covered demographics, frequency and type of animal abuse cases
      seen, awareness of violence towards humans, within families where animal abuse
      was seen, the methods used for managing animal and human abuse, the incidence of
      psychological abuse of animals, and the attitudes of veterinarians towards and
      their beliefs about the link between animal abuse and human violence. RESULTS: A
      total of 383/1,412 (27% response rate) questionnaires with useable data were
      returned. Within the group of respondents, the sexes were evenly represented; 40%
      of respondents worked in small-animal practice, 50% in mixed practice and 10% in
      large-animal practice. Deliberate animal abuse had been seen by 63% of
      respondents in the last 5 years; 37% of these had seen such cases once a year or
      less, while 9% had seen abuse cases at least four times a year. Dogs were the
      species most commonly reported as abused, followed, in numerical order, by cats,
      cattle and horses. Among respondents who had seen deliberate animal abuse, 16%
      either knew of (4%) or suspected (12%) human abuse within the families of the
      abused animals. A clear majority of responding veterinarians agreed with the
      statement that people who abuse their animals are more likely to abuse their
      children (77%) or spouse (70%). CONCLUSIONS: The survey indicated that the
      majority of respondents had seen cases of animal abuse within the previous 5
      years, and dogs were the species most often reported abused. Responding
      veterinarians felt a strong ethical duty to deal with cases of animal abuse, but
      they were less comfortable about issues of human abuse, even though the awareness
      of the link between abuse of animals and abuse of humans was relatively high.
      CLINICAL RELEVANCE: The greater the awareness of animal abuse and its linkage
      with human abuse, the greater the possibility that veterinarians can contribute
      in a meaningful way to the reduction of violence in society.

PMID- 18322557
TI  - Antibiotic resistance among indicator bacteria isolated from healthy pigs in New
      Zealand.
AB  - AIM: To determine the resistance to antibiotics among the indictor bacteria,
      Escherichia coli and Enterococcus spp, isolated from the faeces of healthy pigs
      on three conventional pig farms and one organic farm in the North Island of New
      Zealand. METHODS: Faecal samples, collected at intervals between March and
      October 2001, were plated onto MacConkey agar and Slanetz-Bartley agar and
      examined after 1-3 days incubation for colonies resembling E. coli and
      Enterococcus spp, respectively. Typical colonies were subcultured for further
      identification and storage. The isolates were tested for antibiotic resistance,
      using disc diffusion, to ampicillin, gentamicin, streptomycin, and tetracycline.
      Escherichia coli isolates were also tested for resistance to ciprofloxacin,
      cotrimoxazole and neomycin. Enterococcus spp isolates were also tested for
      resistance to vancomycin, erythromycin and virginiamycin. RESULTS: A total of 296
      E. coli and 273 Enterococcus spp isolates were obtained from the three
      conventional farms, and 79 E. coli and 80 Enterococcus spp isolates were obtained
      from the organic farm. All the E. coli isolates from both the conventional and
      organic pig farms were susceptible to ciprofloxacin, and all the Enterococcus spp
      isolates were susceptible to ampicillin, gentamicin and vancomycin. Isolates of
      E. coli from conventional pig farms were resistant to gentamicin (0.7%), neomycin
      (0.7%), ampicillin (2.7%), cotrimoxazole (11%), streptomycin (25%) and
      tetracycline (60%). Enterococcus spp isolates from the same farms were resistant
      to erythromycin (68%), tetracycline (66%), streptomycin (54%) and virginiamycin
      (49%). By contrast, for the organic pig farm <or=5% of either the E. coli or the
      Enterococcus spp isolates were resistant to any of the antibiotics tested.
      CONCLUSIONS: On commercial pig farms which used antimicrobial agents, there was a
      higher level of antimicrobial resistance in the E. coli and Enterococcus spp
      cultured from the faeces of pigs compared with an organic farm which used no
      antibiotics. Overall levels of antibiotic resistance in the indicator bacteria
      isolated from conventional pig farms in this study were similar to those reported
      for indicator bacteria from pigs in Europe.

PMID- 18322558
TI  - Response of anoestrous ewes pre-treated with a single dose of oestradiol-17 beta,
      or progesterone and oestradiol-17 beta, to the introduction of rams and ewes in
      oestrus.
AB  - AIMS: To determine if the frequency distribution of time to oestrus observed
      after the introduction of rams, and additional ewes in oestrus, is affected by
      the administration of oestradiol- 17beta. To determine if the fertility following
      mating at the first induced oestrus in progesterone-primed ewes may be increased
      with administration of oestradiol-17beta. METHODS: In Experiment 1, ewes received
      40 mug oestradiol- 17beta 3 (E3; n=61) or 5 (E5; n=56) days before the
      introduction of rams; 61 ewes were controls (C1). In Experiment 2, a controlled
      internal drug-releasing (CIDR) device was inserted in 95 ewes on Day -5 (Day 0 =
      introduction of rams). In addition, 47 ewes received oestradiol-17beta on Day 0
      (CE), and the remaining 48 were controls (C2). In both experiments, additional
      ewes, brought into oestrus between Days 0 and 2 by hormonal treatments, were
      introduced with the rams. Onset of oestrus was estimated by visual observation of
      ewes marked by rams. Pregnancy status of ewes in Experiment 2 was determined
      using ultrasound, 30 days after oestrus. RESULTS: The total number of ewes
      detected in oestrus in Experiment 1 was similar between the three groups. The
      frequency distribution of ewes in oestrus in the E5 group differed from that of
      ewes in both C1 (p=0.05) and E3 (p<0.001). A similar number of ewes were detected
      in oestrus between Days 16-20, but the proportion of ewes in oestrus between Days
      21-26 was greater for ewes in C1 than E5 or E3. Mean interval to the onset of
      oestrus was shorter in C1 than E3 which was shorter than E5 ewes (p<0.001). In
      Experiment 2, the total number of ewes in oestrus were similar between groups.
      Ewes in oestrus between Days 1-4 (65% and 64% for C2 and CE, respectively) and
      conception rates over the same period (81% and 80% for C2 and CE, respectively)
      were also similar between groups. CONCLUSIONS: Administration of oestradiol
      17beta to anoestrous ewes altered the pattern of onset of oestrus, but it did not
      affect submission or conception rates, regardless of whether or not a short
      period of progesterone priming with a new CIDR device was included prior to the
      introduction of rams.

PMID- 18322559
TI  - Real-time polymerase chain reaction assays for the detection of members of the
      Mycoplasma mycoides cluster.
AB  - AIM: To develop real-time PCR assays for the detection and differentiation of
      members of the Mycoplasma mycoides cluster. METHODS: Five real-time PCR assays
      were designed to allow differentiation of members of the M. mycoides cluster: an
      assay for detection of the M. mycoides subspecies, viz M. mycoides subsp mycoides
      large colony (MmmLC), M. mycoides subsp capri (Mmc), and M. mycoides subsp
      mycoides small colony (MmmSC); one for the detection of the M. capricolum
      subspecies, viz M. capricolum subsp capricolum (Mcc), M. capricolum subsp
      capripneumoniae (Mccp), and Mycoplasma sp bovine group 7 (BG7); and three for the
      specific detection of MmmSC, Mccp, and BG7. A panel of 74 Mycoplasma isolates
      from various geographical origins and a panel of 21 other bacterial isolates were
      used to evaluate the sensitivity and specificity of the assays. RESULTS: The
      assays displayed 100% analytical sensitivity in detecting all target Mycoplasma
      isolates. The analytical detection limit for the assays to detect the M. mycoides
      subspecies, M. capricolum subspecies, and MmmSC was determined to be 100 fg of
      genomic DNA, while the Mccp and BG7 assays had a detection limit of 100 fg and 10
      fg of genomic DNA, respectively. The M. mycoides subspecies assay had a detection
      limit of 10(3) (SD 10(2)) cfu/ml milk, 10(4) (SD 10(4)) cfu per swab, and 10(3)
      (SD 10(3)) cfu/g lung in inoculated samples. The assays displayed 100%
      specificity when applied to non-target bacterial isolates and to 110 culture
      negative milk samples. CONCLUSIONS: The assays were highly sensitive and
      specific, and provide accurate detection and differentiation of the members of
      the M. mycoides cluster.

PMID- 18322560
TI  - Re: Analysis of the risk of introduction and spread of porcine reproductive and
      respiratory syndrome virus through importation of raw pigmeat into New Zealand.

PMID- 18322563
TI  - Analysis of an SIR epidemic model with pulse vaccination and distributed time
      delay.
AB  - Pulse vaccination, the repeated application of vaccine over a defined age range,
      is gaining prominence as an effective strategy for the elimination of infectious
      diseases. An SIR epidemic model with pulse vaccination and distributed time delay
      is proposed in this paper. Using the discrete dynamical system determined by the
      stroboscopic map, we obtain the exact infection-free periodic solution of the
      impulsive epidemic system and prove that the infection-free periodic solution is
      globally attractive if the vaccination rate is larger enough. Moreover, we show
      that the disease is uniformly persistent if the vaccination rate is less than
      some critical value. The permanence of the model is investigated analytically.
      Our results indicate that a large pulse vaccination rate is sufficient for the
      eradication of the disease.

PMID- 18322564
TI  - The economic impact of a college of pharmacy.
AB  - OBJECTIVES: To quantify the dollar value of economic returns to a community when
      a college of pharmacy attains its fourfold mission of research, service, patient
      care, and education. METHODS: United States Bureau of Economic Analyses (BEA)
      RIMS II input/output analysis and data from student and faculty surveys were used
      to quantify the economic impact of the University of Tennessee's College of
      Pharmacy (UTCOP). RESULTS: The UTCOP's revenue of $22.4 million resulted in an
      indirect output impact of over $29.2 million, for a total impact of nearly $51.6
      million in output (production of goods and services), while supporting 617.4 jobs
      and total earnings of $18.5 million during the 2004-2005 school year.
      CONCLUSIONS: Demonstrating the economic value of colleges of pharmacy is critical
      when seeking support from state legislators, foundations, government agencies,
      professional associations, and industry. Based on this study, UTCOP was able to
      report that every dollar the state invests in UTCOP yields an estimated net
      return on investment of $27.90.

PMID- 18322565
TI  - Work profiles identified from the 2007 Pharmacist and Pharmaceutical Scientist
      Career Pathway Profile Survey.
AB  - OBJECTIVES: To investigate the underlying factor structure of respondents' work
      profiles that were created using the 48 items in the Career Pathway Evaluation
      Program, 2007 Pharmacist and Pharmaceutical Scientist Profile Survey, and use the
      resulting factors to describe the 26 different work categories listed in the
      survey. METHODS: Exploratory factor analysis was used to describe the underlying
      structures (factors) that best represented respondents' work profiles.
      Descriptive statistics and analysis of variance were used to describe the 26
      different work categories listed in the survey. RESULTS: Ten underlying factors
      were identified for the respondents' work profiles. A description of these
      factors among the 26 different respondent categories revealed variation among the
      categories that can be useful for describing the career categories in the
      American Pharmacists Association Career Pathway Evaluation Program. CONCLUSIONS:
      Variations in work settings among various pharmacy careers were identified. The
      profiles constructed in this study could be helpful to individuals as they
      consider various career paths and choose elective coursework or experiential
      sites during their pharmacy education.

PMID- 18322566
TI  - Assessment of factors influencing community pharmacy residents' pursuit of
      academic positions.
AB  - OBJECTIVES: To determine the percentage of residents accepting faculty positions
      following completion of a community pharmacy residency program (CPRP) and
      identify influences to pursue/not pursue an academic career. METHODS: CPRP
      directors and preceptors across the United States were contacted and 53 community
      pharmacy residents were identified. The residents were invited to participate in
      surveys at the beginning and end of the 2005-2006 residency year. RESULTS: Forty
      five residents (85%) completed the preliminary survey instrument and 40 (75%)
      completed the follow-up survey instrument. Of these, 36 completed both survey
      instruments. Initially, 28 (62%) respondents indicated a faculty position as one
      of their potential job preferences. After completing their residency program, 3
      (8%) residents accepted faculty positions; and 3 (8%) others were awaiting offers
      at follow-up. Reasons for accepting a faculty position were positive teaching
      experiences and the influence of a mentor or preceptor. Reasons for not pursuing
      a faculty position included lack of interest, geographic location, disliked
      teaching experiences, lack of preparedness, and non-competitive salary.
      CONCLUSION: Many community pharmacy residents consider faculty positions early in
      their residency but few pursue faculty positions. CPRPs and colleges of pharmacy
      should work together to enhance residents' experiences to foster interest in
      academia.

PMID- 18322567
TI  - Pharmacy students' preferences for various types of simulated patients.
AB  - OBJECTIVE: To evaluate pharmacy students' preferences for various types of
      simulated patients. METHODS: Second-professional year (P2) pharmacy students
      participated in 7 learning activities that used simulated patients including
      community volunteers, College administrative staff, course instructors, and
      student peers. Students ranked each simulated patient type according to
      believability, skill development, and preference using a 5-point Likert scale.
      RESULTS: One-hundred seven of 155 students (69%) completed the survey instrument.
      Students preferred community volunteers as simulated patients (mean rank 1.39),
      followed by peers (2.22), instructors (2.63), and staff members (2.81) (p <
      0.001). Greater than 89% agreed or strongly agreed that their work with simulated
      patients prepared them for actual patients, with community volunteers receiving
      the highest ratings (p < 0.03). CONCLUSIONS: Although pharmacy students found
      value in interactions will all types of simulated patients, they preferred
      community volunteers over staff members and their peers. Future scholarship
      should explore the relationship among simulated patient types and student
      learning outcomes.

PMID- 18322568
TI  - A categorization scheme for assessing pharmacy students' levels of reflection
      during internships.
AB  - OBJECTIVE: To test the reliability, feasibility, and responsiveness of a
      categorization scheme for assessing pharmacy students' levels of reflection
      during internships. METHODS: Pharmacy interns at Uppsala University were asked to
      write a reflective essay about patient counseling at the start and end of their
      internships. A modified version of Kember's categorization scheme for assessing
      the level of reflection was used to evaluate these essays. RESULTS: Based on
      their essay scores, the students' levels of reflection increased during the
      internship course (p < 0.001) The mean time for categorization was 3 minutes per
      essay. The interrater reliability of the 182 essays was kappa = 0.63.
      CONCLUSIONS: The evaluation of the categorization scheme showed that it has good
      interrater reliability, feasibility, and responsiveness. This scheme might be
      useful in pharmacy practice educational settings, but needs further validation.

PMID- 18322569
TI  - First-year residency candidates' experience in various areas of pharmacy
      practice.
AB  - OBJECTIVE: To determine the extent of experience or exposure pharmacy residency
      candidates had in various areas of hospital pharmacy practice and to identify any
      candidate-specific variables that correlated with a larger extent of experience.
      METHODS: Over a 3-year period, a self-assessment survey instrument was
      administered to 116 postgraduate first-year (PGY1) pharmacy practice residency
      candidates to evaluate their extent of experience within various areas of
      hospital pharmacy practice such as patient care activities, drug information, and
      drug distribution/control. RESULTS: The residency candidates reported the
      greatest amount of experience in patient counseling, working with pharmacy
      databases, taking medication histories, pharmacokinetics, and outpatient
      dispensing procedures. They had less experience with medical emergencies,
      parenteral nutrition, and intravenous admixture techniques. Overall, there was no
      correlation between class rank, advanced pharmacy practice experiences,
      geographic region, or year of interview and the extent of candidates' experience
      in any specific area of pharmacy. CONCLUSION: PGY1 residency candidates in this
      sample reported minimal experience in areas necessary for hospital pharmacy
      practice and this suggests possible deficiencies in the PharmD curriculum. PGY1
      residency programs in acute care settings should recognize these educational
      deficits and assure that residents have exposure to and develop proficiency in
      critical areas such as medical emergencies, parenteral nutrition, and intravenous
      admixture techniques.

PMID- 18322570
TI  - Doctor of pharmacy students' use of personal digital assistants.
AB  - OBJECTIVES: To describe the use of personal digital assistants (PDAs) by doctor
      of pharmacy (PharmD) students; determine the reliability of psychometric
      constructs that determine technology acceptance; and determine constructs that
      directly correlate with PDA use. METHODS: A survey instrument was developed
      containing descriptive and psychometric items and administered to PharmD students
      at 2 universities. RESULTS: Over half of new users (58.1%) and experienced users
      (51.3%) reported using their PDA at least weekly. Eighty-four percent of
      experienced users used their PDA at least weekly to look up drug information. The
      most reliable scales were perceived usefulness (alpha = 0.92), perceived ease of
      use (alpha = 0.89), and attitude towards behavior (alpha = 0.84). Intention to
      use and self-reported use of PDAs were strongly correlated with perceived
      usefulness, attitude towards behavior, and compatibility. CONCLUSIONS: The
      majority of pharmacy students used their PDAs at least weekly and find them most
      useful for looking up drug information.

PMID- 18322571
TI  - Evaluation of curricula content based on Thai pharmacy competency standards.
AB  - OBJECTIVE: To evaluate the curricula content of Thai pharmacy schools based on
      the Thai pharmacy competency standards. METHODS: Course syllabi were collected
      from 11 pharmacy schools. A questionnaire was developed based on the Thai
      pharmacy competency standards. Course coordinators completed the questionnaire
      assessing the curricula content. RESULTS: The curricula for both the bachelor of
      science in pharmacy degree (BS Pharm) and doctor of pharmacy (PharmD) degree
      programs included the minimum content required by the 8 competency domains. The
      dominant content area in BS Pharm degree programs was product-oriented material.
      The content ratio of patient to product to social and administrative pharmacy in
      the BS Pharm degree programs was 2:3:1, respectively. However, the content ratio
      suggested by the Thai Pharmacy Council was 3:2:1, respectively. For the PharmD
      programs, the largest content area was patient-oriented material, which was in
      agreement with the framework suggested by the Thai Pharmacy Council. CONCLUSIONS:
      The curricula of all Thai pharmacy schools met the competency standards; however,
      some patient-oriented material should be expanded and some product-oriented
      content deleted in order to meet the recommended content ratio.

PMID- 18322572
TI  - Online social networking issues within academia and pharmacy education.
AB  - Online social networking sites such as Facebook and MySpace are extremely popular
      as indicated by the numbers of members and visits to the sites. They allow
      students to connect with users with similar interests, build and maintain
      relationships with friends, and feel more connected with their campus. The
      foremost criticisms of online social networking are that students may open
      themselves to public scrutiny of their online personas and risk physical safety
      by revealing excessive personal information. This review outlines issues of
      online social networking in higher education by drawing upon articles in both the
      lay press and academic publications. New points for pharmacy educators to
      consider include the possible emergence of an "e-professionalism" concept; legal
      and ethical implications of using online postings in admission, discipline, and
      student safety decisions; how online personas may blend into professional life;
      and the responsibility for educating students about the risks of online social
      networking.

PMID- 18322573
TI  - Best practices for survey research reports: a synopsis for authors and reviewers.

PMID- 18322574
TI  - Dual degree programs at the University of Kentucky College of Pharmacy.
AB  - The rapid growth and evolution of the pharmacy profession has created a wide
      array of opportunities for graduating pharmacists beyond traditional community
      pharmacy or hospital practice. Management and leadership positions in federal and
      state healthcare agencies, pharmaceutical companies, hospitals, retail
      pharmacies, academia and managed care organizations increasingly require the
      pharmaceutical knowledge obtained through a doctor of pharmacy (PharmD) degree
      combined with financial, organizational, and management skills. In these
      innovative positions, pharmacists are being called upon to assume
      responsibilities as executives and administrators in systems providing pharmacist
      care services to patients. To endow students with knowledge and skills required
      to perform the duties required in these decision-making positions, the University
      of Kentucky College of Pharmacy has established 3 joint degree programs: the
      PharmD/Master of Business Administration (PharmD/MBA), PharmD/Master of Public
      Administration (PharmD/MPA), and PharmD/Master of Science in Economics
      (PharmD/MS). This paper describes these joint degree programs.

PMID- 18322575
TI  - AACP pharmacy education assessment services: outcomes, assessment,
      accountability.

PMID- 18322576
TI  - Increasing the representation of underrepresented minority groups in US colleges
      and schools of pharmacy.

PMID- 18322577
TI  - Making the most of pharmacy school.

PMID- 18322578
TI  - A decade of pharmacy practice education in India.

PMID- 18322579
TI  - Experiences with an elective in spirituality.

PMID- 18322580
TI  - An advanced pharmacy practice experience in sports pharmacy.
AB  - OBJECTIVE: To establish and evaluate an advanced pharmacy practice experience
      (APPE) in sports pharmacy. DESIGN: Students actively participated in a variety of
      activities for this new 6-week elective APPE, including drug-testing collections,
      delivering presentations, and providing drug information. Students also learned
      about assays, compounding, and dispensing medications specifically for athletes,
      and visited various athletic medical facilities. Student were given written and
      practical certification examinations for drug-testing collections, and their
      specimen measurements were compared to those obtained by the testing laboratory
      for validation; satisfaction surveys were obtained from testing sites; and
      presentation evaluations were obtained from audience participants. ASSESSMENT:
      Students were able to accurately measure pH and specific gravity of urine samples
      and all students passed the certification examination. Students rated the APPE
      very high. Also, students received high satisfaction ratings on surveys
      administered to the officials of the schools where they tested and members of the
      groups to whom they gave presentations. CONCLUSION: Students gained experience
      and insight into the various roles of pharmacists in sports pharmacy and
      developed confidence in their ability to conduct drug-testing collections.

PMID- 18322581
TI  - An active-learning assignment using nonprescription medicines.
AB  - OBJECTIVE: To create and implement a web-based written assignment to evaluate
      student's abilities to select appropriate nonprescription medications and
      recommend therapy. DESIGN: Each student developed a patient case study from an
      assigned condition, made treatment recommendations, and provided patient
      counseling information using at least 2 nonprescription medicines. The active
      learning exercise required students to apply information previously presented in
      a large classroom setting. ASSESSMENT: Cases most commonly submitted included
      therapy for burns, acne, conjunctivitis, lacerations, and poison ivy. One-hundred
      five students completed a 5-item questionnaire regarding the assignment. The
      majority of the respondents (51.9%) felt the assignment helped to reinforce
      course content and 58.1% felt it made them more comfortable with making product
      recommendations. CONCLUSION: The Personal Pharmacy assignment was an effective
      learning activity for enhancing student's understanding and appropriate selection
      of nonprescription medicines.

PMID- 18322582
TI  - Using game format in small group classes for pharmacotherapeutics case studies.
AB  - OBJECTIVE: To incorporate games in classroom teaching to encourage student
      interest and participation in a small group pharmacy therapeutics case studies
      class. DESIGN: Using a television quiz show and classic board game format,
      students and the instructor developed games to discuss patient care plans. At the
      end of the course, a questionnaire was administered to assess students' attitudes
      and perception of using game format in the class and whether this teaching method
      was useful in reinforcing therapeutic knowledge. ASSESSMENT: The majority of the
      students felt that games were beneficial in their learning process. The game
      format also resulted in higher student participation scores. CONCLUSIONS: The
      game-format approach to learning aroused student interest, enhanced
      participation, and improved their participation grades. Although the game format
      of leaning is an effective way of actively engaging students in higher leaning,
      determining how these games improve test scores will require further assessment.

PMID- 18322583
TI  - [Screening and application of enhancer-like sequences from vaccinia virus].
AB  - OBJECTIVE: To screen enhancer-like sequences from vaccinia virus genome, to
      construct an expression vector harboring prokaryotic enhancer-like sequence and
      study the effect of interferon gene expression. METHODS: Enhancer-like element
      from vaccinia virus genome was obtained by using the chloramphenicol acetyl
      transferase cat gene as reporter gene. An expression vector harboring prokaryotic
      enhancer-like sequence VV1 from vaccinia virus was constructed. Interferon was
      expressed and assayed. RESULTS: Eighteen enhancing sequences were found. From
      them two enhancer-like sequences with distance and orientation independence
      property were screened and named VV1 and VV16 respectively. Quantification test
      showed that the direct and reverse orientation of VV1 could increase the activity
      of beta-galactosidase with 10.9 and 3.8 times and those of VV16 could increase by
      9.0 times and 4.1 times respectively. The enhancing activity of the element was
      on transcription level. An expression vector harboring prokaryotic enhancer-like
      sequence VV1 was constructed. Using this vector the antiviral activity of
      interferon alpha-2b was increased by 2.6 times in comparison with the original
      expression plasmid. CONCLUSION: Two enhancer-like sequences were screened from
      vaccinia virus genome. Interferon gene was highly expressed by using an
      expression vector harboring enhancer-like sequences.

PMID- 18322584
TI  - [Antigenic and genetic study of influenza virus circulated in China in 2006].
AB  - OBJECTIVE: To analyse seasonal influenza epidemic situation in 2006, and to
      analyse the genetic and antigenic characteristics of viral hemagglutinin (HA)
      gene. METHODS: The single-way hemagglutination inhibition (HI) tests were used to
      test the antigenic characteristics of these viruses from influenza surveillance
      network, and the HA1 genes were sequenced based on the antigenic test results
      according to different isolation times and sites. RESULTS: The influenza virus
      types A and B co-circulated in 2006. influenza A H1N1 subtype and Victoria-like B
      influenza circulated preponderantly during this epidemic season. The HA1 gene
      sequence of H1N1 viruses showed that 192, 193, 196, 198 positions (located at
      antigenic site B) have an amino acid substitute, compared with the last
      circulating strain A/Hubeihongshan/53/2005(H1N1). Two amino acid changes at 142
      and 144 positions compared with A/Yunnan/1145/2005 (H3N2). There was no change in
      influenza B viruses either Victoria-like B or Yamagata-like B virus, i.e .
      antigenic characteristics is analogous to B/shenzhen/155/2005 and
      B/tianjin/144/2005, respectively. CONCLUSION: The H1N1 and H3N2 influenza viruses
      had changing antigenic and genetic characteristics in 2006. Influenza virus types
      B did not change in 2006.

PMID- 18322585
TI  - [Detection the coinfection of Hantavirus and Orientia tsutsugamushi in primary
      cultured mite cells].
AB  - OBJECTIVE: To investigate whether HV and Ot can coexist in their host
      (Leptotrombidium scutellare). METHODS: Collecting the separate Leptotrombidium
      scutellare and the ones from mice in epidemic area. The cells of mites at larva,
      nymph, and adult stages were cultured and made into smear. In situ RT-PCR and PCR
      were used to detect and locate HV RNA and Ot DNA in the primary cultured cells.
      RESULTS: Positive signals of HV RNA and Ot DNA distributed mostly in epithelial
      cells of digestive system and ovary cells of larva and nymph. The positive rate
      increased by the generation of passages. CONCLUSION: Coinfection of HV and Ot did
      exist in wild Leptotrombidium scutellare.

PMID- 18322586
TI  - [Cyclosporine A improves the nuclear entry of hepatitis B virus core protein in
      HepG2.2.15 cells].
AB  - OBJECTIVE: The present aimed to observe the effect of phosphatase inhibitor
      cyclosporine A on the subcellular location and on expression of HBcAg in
      HepG2.2.15 cells. METHODS: Thirty micrograms/ml of cyclosporine A (CSA) was added
      into HepG2.2.15 cell culture system and on days 2 and 4 HBcAg and HBsAg were
      respectively stained with fluorescent immunocytochemistry and observed under
      confocal microscope. Cell apoptosis was detected by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labelling method. RESULTS: HBcAg was mostly
      expressed in cytoplasm in the control HepG2.2.15 cells. After 2 days CSA
      administration of the expression of HBcAg and HBsAg in cytoplasm significantly
      decreased and the signals of HBcAg in nucleus increased , whereas the HBcAg was
      still mainly expressed in nucleus in about 1/4 of the cells. Cell apoptosis was
      observed in about 30% of the cells. CONCLUSION: CSA improves the nuclear entry of
      core protein. The increase of HBcAg in nucleus was likely to be related with it's
      phosphorylation and cell aging or apoptosis.

PMID- 18322587
TI  - [Molecular-biological identification of pathogens which caused an outbreak of
      viral encephalitis in Jinan area].
AB  - OBJECTIVE: To investigate the etiology of the outbreak of viral encephalitis in
      Jinan area in 2003. METHODS: Virus-specific nucleic acid fragments were amplified
      by random PCR and RT-PCR using specific primers to enterovirus. After sequencing,
      the gene sequence was handled by the program BLAST for homologous analysis and
      the software Clustal W 1.82 for multiple sequence alignment to identify the
      etiology and its genotype. RESULTS: Five strains were isolated from clinical
      specimens. A gene fragment for one strain was acquired using random PCR, which
      was highly homologous to enterovirus. Then, the 5' non-translated region and
      partial VP1 region were amplified and sequenced. The five isolated strains were
      all identified as Coxsackievirus B5, and what was more, they were most homologous
      to the strain isolated during the outbreak of aseptic meningitis and encephalitis
      in Zhejiang province from 2002 to 2004. CONCLUSION: Coxsackievirus B5 is closely
      associated with the outbreak of viral encephalitis in Jinan area in 2003. It is
      an important etiology but other viruses may also played a role which remains to
      be clarified.

PMID- 18322588
TI  - [Relation between acute respiratory infection and enterovirus in children in
      Beijing area].
AB  - OBJECTIVE: To probe into the relation between acute respiratory infection and
      enterovirus (EV), season, age and sex of children in Beijing area. METHODS:
      Nasopharyngeal secretion samples from 402 inpatient children with acute
      respiratory infection (ARI) were obtained, and EV RNA was detected by reverse
      transcriptase polymerase chain reaction (RT-PCR). The distribution of month, age
      and sex among the children positive for EV were analyzed. RESULTS: Seventy of the
      402 cases were positive for EV RNA, the positive rate was 17.4 percent. The EV
      positive rate was 17.7 percent in children with lower respiratory tract
      infection, and 15.9 percent in children with upper respiratory tract infection.
      The EV positive rates were 0-36.1 percent in different months, which was the
      highest in the May (36.1 percent) and lower in December (4.3 percent). The
      positive rate of EV was 14.8 percent-21.9 percent in different age groups except
      for children 12 years of age and older, the positive rate was the lowest in the 4
      6 years age group, and the highest in the 7 month-1 year age group. The EV
      infected boys and girls accounted for 16.2 percent and 19.7 percent of total
      numbers of boys and girls, respectively. CONCLUSION: The EV positive rate was
      higher in children with lower respiratory infection, which suggests that EV may
      play an important role in ARI of children. The EV positive rate was higher from
      late spring to autumn. EV infection was common in children under 12 years of age.
      The rate of EV infection was not significantly different between boys and girls.

PMID- 18322589
TI  - [Effect of short interfering RNAs on hepatitis C Virus 5' untranslated region
      expression].
AB  - OBJECTIVE: To evaluate interfering effect of several short interfering RNAs
      (siRNA) on HCV 5' untranslated region(5' UTR). METHODS: The green fluorescent
      protein (GFP) was used as reporter gene. A fused gene of HCV-5'UTR and GFP was
      constructed. It was cloned into the plasmid pCDNA3.1 named as pcDNA-HCV-5'UTR
      GFP. Three siRNAs were designed and transfected into HepG2 cells with pcDNA-HCV
      5'UTR-GFP. The change of the fluorescence intensity of HepG2 cells was shown by
      fluorescence microscopy and numerically detected under 488 nm wave length by flow
      cytometry. RESULTS: The fused gene of HCV-5'UTR and GFP was successfully
      constructed. The seven groups displayed inhibitory effects on the gene expression
      of GFP. The inhibition rates of siRNA A, B and C were 68.4 percent, 72.6 percent
      and 75.6 percent, respectively. The inhibitory rates of siRN A + B, siRN B +C and
      siRN A +C were 91.8 percent, 87.2 percent and 92.4 percent, respectively. The
      inhibitory rates of siRN A+B +C was the highest, up to 95.7 percent. CONCLUSION:
      These siRNAs could inhibit expression of HCV 5'UTR gene, the inhibitory effect of
      combined siRNA was better than that of single siRNAs.

PMID- 18322590
TI  - [Polymorphisms of human cytomegalovirus UL139 open reading frame in
      Hirschsprung's disease].
AB  - OBJECTIVE: To explore the UL139 gene polymorphism of human cytomegalovirus
      (HCMV), and the relationship between polymorphisms of HCMV UL139 ORF and
      Hirschsprung's disease (HD). METHODS: Forty-three specimens of the aganglionic
      intestinal segment and 6 urine samples of HD infants were amplified by nested
      polymerase chain reaction (PCR) method. The amplicons were sequenced in both
      strands directly. The control group consisted of 10 asymptomatic HCMV infected
      infants, and their urine specimens were also analyzed using the same method.
      RESULTS: HCMV UL139 genes of 28 clinical strains from HD 1 patients were
      successfully amplified and sequenced. UL139 was hypervariable and was clustered
      into 3 major groups and 5 genotypes. The predominant genotype of HCMV in HD
      infants was UL139 Group 3 (48 percent). Comparison of strains distribution
      between the two groups did not reach statistical significance using chi square
      test (chi square=7.378, P=0.194). The results of correlation analysis between
      UL139 and UL144 genes showed a p value 0.05 by Kendall test. Clinically, strains
      from the rectosigmoid segment, total colon aganglionosis, and long-segment were
      distributed sporadically in UL139 genotypes. CONCLUSION: UL139 gene displayed
      polymorphisms. No linkage was found between UL139 genotype and clinical phenotype
      of HD. There was no correlation between HCMV UL144 and UL139.

PMID- 18322591
TI  - [An analysis of the clinical characteristics of patients with chronic hepatitis B
      superinfected with acute hepatitis E].
AB  - OBJECTIVE: To investigate clinical features of the patients with hepatitis B
      superinfected with acute hepatitis E (AHE). METHODS: Totally 625 consecutive
      patients enrolled from Dec 2002 to Dec 2006 were studied retrospectively. All of
      the patients were subclassified into acute hepatitis E group (AHE=437 cases) and
      Superinfected Group (S=188 cases), and S group was further divided into the group
      of chronic hepatitis B superinfected with acute hepatitis E (CHB+AHE, 130 cases)
      and the group of liver cirrhosis and hepatitis B superinfected with acute
      hepatitis E (LCB+AHE, 58 cases). In 32 of the 188 superinfected patients the
      effects of HEV on HBV were observed by comparing the levels of HBV DNA in acute
      vs. convalescence stages. RESULTS: Compared with the patients with AHE, the
      superinfected patients had a higher level of total bilirubin (TBil), an elevated
      frequency of fulminate hepatitis, mortality and a longer period of the mean
      hospital stay for the cured patients but significantly lower levels of alanine
      aminotransferase (ALT), serum albumin and prothrombin activity (PA). Furthermore,
      the group of LCB+AHE had a higher level of TBil and higher incidences of
      complications such as ascites, peritonitis, hepatic encephalopathy and
      disturbance in glycometabolism than the group of CHB+AHE. The follow-up for the
      superinfected patients showed that 20 of 32 patients (62.5 percent) had decreased
      copies of HBV DNA during the recovery phase compared with the acute phase, and
      the mean decrease of HBV DNA was 2.1 log10. The HBV DNA was in a persistently
      undetectable level in 6 of 32 (18.8 percent) superinfected patients. However, 4
      of 32 patients (12.5 percent) showed an unchanged levels of HBV DNA and 2 cases
      (6.2 percent) had a slightly increased HBV DNA levels. CONCLUSION: Superinfection
      with AHE in patients with chronic hepatitis B leads to a more severe hepatic
      damage and the replication of HBV DNA can be transiently inhibited.

PMID- 18322592
TI  - [Co-expression of HSV-1 gD gene and interleukin-2 gene in dendritic cell].
AB  - OBJECTIVE: To construct eukaryotic expression plasmid IRES-gD-IL-2 which contains
      both HSV-1 glycoprotein D (gD) gene and IL-2 gene and to induce it to express in
      antigen presenting cell (APC) -- dendritic cells (DCs). METHODS: The whole
      sequence of gD and IL-2 were amplified by PCR assay. After confirmation by PCR,
      double-enzyme digestion and sequencing, these genes were directly cloned into
      eukaryotic expression vector IRES, then were transfected into DCs. Western
      blotting was employed to identify the transcription and expression of gD gene.
      RESULTS: The results of PCR and enzyme digestion showed that the recombinant
      expression plasmid contained correct fragments, and the transcription and
      expression of gD were confirmed by Western blotting. CONCLUSION: The recombinant
      expression vector IRES-gD-IL-2 was constructed, the results of the Western
      blotting showed that the recombinant protein could be identified by gD- specific
      antibody, therefore the protein has immunologic competence.

PMID- 18322593
TI  - [Clinical prospective study on maternal-fetal transmission of human bocavirus].
AB  - OBJECTIVE: To investigate maternal-fetal transmission at human bocavirus (HBoV).
      METHODS: IgG antibody to HBoV in serum samples of 316 mothers were determined
      with ELISA and HBoV DNA was determined with real time PCR in the sera of the
      mothers and their infants. RESULTS: HBoV-IgG was positive in 40.20 percent
      (127/316) of the mothers, while it was positive in 29.43 percent (93/316) of the
      cord blood specimens of the infants. The difference between the two groups was
      significant (X2=8.12, P less than 0.005); 93 samples of both the mothers and the
      infants were positive for HBoV-IgG. CONCLUSION: HBoV-IgG can cross the placenta
      to the fetuses through placenta. Further study is needed to answer the question
      whether vertical maternal-fetal transmission occurs.

PMID- 18322594
TI  - [Specific T cell immune response in chronic hepatitis B patients treated with
      different doses of recombinant hepatitis B vaccine].
AB  - OBJECTIVE: To study the specific cellular immunoresponse of peripheral blood
      lymphocytes in the chronic hepatitis B patients treated with different doses of
      recombinant hepatitis B vaccine. METHODS: Seventy-two chronic hepatitis B
      patients who did not use any anti-HBV drugs within 6 months were randomized into
      3 groups (90 micrograms, 60 micrograms, and placebo) in a ratio of 1:1:1. The
      patients in different groups were treated with different doses of recombinant
      hepatitis B vaccine in combination with IFN alpha 1b 50 micrograms with 3 times a
      week for 24 weeks. All patients were followed up for 24 weeks (W24). HBV DNA,
      HBeAg and liver functions were detected at different time points, and the number
      of cells that secrete IFN-gamma were detected by ELISPOT. RESULTS: There were no
      significant difference in ELISPOT positive ratio among the 3 groups on baseline
      detection. At W24, 12 cases, 12 cases, and 7 cases showed ELISPOT positive in the
      group of 90 micrograms, 60 micrograms, and placebo. The proportion of patients
      who were ELISPOT positive was higher in the groups treated with recombinant
      hepatitis B vaccine (including the dose of 90 micrograms and 60 micrograms) than
      that in the placebo group (P=0.0446). HBV DNA turned negative in 6/24 of the
      patients treated with recombinant hepatitis B vaccine (at both the doses of 90
      micrograms and 60 micrograms), and HBeAg/Anti-HBe seroconversion or HBeAg became
      negative in 7/24 of them. In the placebo group, none of the patients showed
      undetectable HBV DNA, HBeAg/Anti-HBe seroconversion or HBeAg disappearance. At
      the 24W of follow up, in the patients who were ELISPOT positive, HBV DNA became
      undetectable in 4 of the patients treated with recombinant hepatitis B vaccine
      (at doses of 90 micrograms and 60 micrograms), and HBeAg/Anti-HBe seroconversion
      or HBeAg disappearance were found in 9 of the cases. In the placebo group, none
      of the cases showed undetectable HBV DNA, and only 1 case had HBeAg/Anti-HBe
      seroconversion. CONCLUSION: The recombinant hepatitis B vaccine may increase the
      function of specific T lymphocytes in patients with chronic hepatitis B. There
      were no significant differences between the patients treated with the dose of 90
      micrograms and 60 micrograms hepatitis B vaccine.

PMID- 18322595
TI  - [CD4+CD25+high regulatory T cells in patients with autoimmune hepatitis].
AB  - OBJECTIVE: To investigate the role of CD4+CD25+high regulatory T cells in the
      pathogenesis of autoimmune hepatitis. METHODS: CD4+CD25+ high regulatory T cells
      and CD4+ T cells were measured by using flow cytometry in 16 patients with
      autoimmune hepatitis, 22 patients with chronic hepatitis B and 20 healthy blood
      donors. Foxp3 protein was detected by immunohistochemical assay in liver tissues
      from the patients with autoimmune hepatitis or chronic hepatitis B. RESULTS: The
      percentage of CD4+CD25+high/CD4+ in patients with autoimmune hepatitis was
      significantly lower than that in healthy controls and patients with chronic
      hepatitis B. Meanwhile, the percentage of CD4+CD25+high/CD4+ highly increased in
      patients with chronic hepatitis B, compared with healthy controls; Foxp3 positive
      cells were mostly located in the hepatic lobular perisinusoidal spaces and the
      portal tract, and there was a significant difference in the quantity of Foxp3
      positive cells between patients with autoimmune hepatitis and chronic hepatitis
      B. CONCLUSION: Patients with autoimmune hepatitis harbor a decreased percentage
      of CD4+CD25+ high regulatory T cells, which may be associated with development of
      autoimmunity.

PMID- 18322596
TI  - [Effect of Nocardia rubra cell wall skeleton (Nr-CWS) on oncogenicity of TC-1
      cells and anti-human papillomavirus effect of Nr-CWS in lower genital tract of
      women].
AB  - OBJECTIVE: To detect the effect of Nocardia rubra cell wall skeleton (Nr-CWS) on
      tumorigenicity induced by TC-1 cells and to clinically study anti-human
      papillomavirus effect of Nr-CWS in lower genital tract of women. METHODS: Tumor
      model was established by injecting TC-1 cells subcutaneously in SCID mice, then
      divided them into 3 groups randomly and injected with isovolumetric physiological
      saline, 60 micrograms/ml Nr-CWS and 120 micrograms/ml Nr-CWS respectively, the
      growth of tumors was measured one week later. Nr-CWS was applied on 45 HPV
      positive women whose TCT test was normal and without cervical erosion 2-3 days
      after menstruation. HPV was detected again 3 months later to explore the effect
      of Nr-CWS on HPV infection in female lower genital tract. RESULTS: The animal
      experiment showed the weight of transplanted tumors in treated group was less
      than that of control group (chi2=12.5, P= 0.002). The tumor inhibition rate was
      59.1 percent and 84.2 percent in the groups treated with Nr-CWS 60 and 120
      micrograms/ml Nr-CWS; the results of HPV detection in 23 out of the 45 cases
      (51.1 percent) became negative after the 3-month treatment; the viral load was
      reduced in 9, and there was no change in viral load in 13 cases. Significant
      difference was found between the rates of undetectable viral load and the natural
      viral disappearance rate (P less than 0.05). CONCLUSION: Nr-CWS has an inhibitory
      effect to TC-1 cell tumorigenesis and clinical application of Nr-CWS may
      eliminate the HPV infection in lower genital tract of a considerable proportion
      of women with HPV infection.

PMID- 18322597
TI  - [Molecule character of rabies virus in 3 counties in Hunan China].
AB  - OBJECTIVE: To study the rabies molecular biology features in animals between high
      incidence area of rabies and no rabies cases area in Hunan. METHODS: detect
      saliva of dogs and brains of dogs and cats by direct immunofluorescence assay,
      review positive samples by RT-PCR, sequencing extract RNA virus for genetic
      analysis. RESULTS: 12 were detected rabies virus antigen and positive nucleoside
      acid in 82 dogs from Wugang city also 1 in 17 from Dongkou county; the positive
      rate: Wugang 14.63 percent, Dongkou 5.88 percent. No rabies virus was detected in
      67 samples of dog brains from Fenghuang County. Also none in 28 samples of cat
      brains. Amplificating N gene of rabies virus from positive samples of dog brain's
      tissue (No Wg13, Dk13) by RT-PCR, it shows that homology of nucleoside acid
      between two strain of virus is 99.4 percent; also 99.1 percent of amino acid. The
      homology of nucleoside acid (amonio acid) among Wg13 stain and Chinese strain CTN
      and aG strain is 89.4 percent (98.2 percent) and 86.1 percent (95.1 percent); The
      homology of nucleoside acid (amonio acid) among Dk13 stain Chinese strain CTN and
      aG strain is 89.1 percent (98.0 percent), 86.1 percent (94.9 percent).Compare
      with isolated rabies virus from abroad, the homology between two strains and
      Indonesia is 92.8 percent and 93.2 percent, the most similar of them. The strains
      isolated from other countries including Japan, Sri Lanka and India are relatively
      lower; The sequence of gene Wg13 and Dk13 were taken replacement of amino acid.
      CONCLUSION: Two strains are belong to type I rabies virus, comparing its N gene
      with current using vaccine strains, both are in same group, and homology are
      relatively higher.

PMID- 18322598
TI  - [Preparation of armored RNA containing M gene of influenza H3N2].
AB  - OBJECTIVE: To prepare the armored RNA containing M gene of influenza H3N2.
      METHODS: The vector pAR-1 was constructed from expression vector pET30b in which
      the bacteriophage MS2 DNA fragment, containing the genes for maturase and coat
      protein and the pac site, was inserted. The M gene fragment of influenza A was
      inserted into the HindIII site downstream of the pac site on the pAR-1, which
      formed a new recombinant plasmid pAR-2. After the prokaryotic expression was
      carried out, armored RNA AR-2 containing M gene was obtained. AR-2 was purified,
      and then was quantified by real time RT-PCR. Moreover, the stability of AR-2 was
      checked. RESULTS: AR-2 was expressed successfully. AR-2 remained stable under
      various storage environments. Approximately 8.9 x 10(11) copies of AR-2 particles
      can be purified from one milliliter of culture. CONCLUSION: It showed that AR-2
      was stable and RNase-resistant, which, as a virus surrogate, would be used as RT
      PCR standards, controls and training or proficiency samples.

PMID- 18322599
TI  - [Proteomic analysis of hepatitis B virus-infected human liver tissues].
AB  - OBJECTIVE: To search for the difference of protein molecules expression of HBV
      infection. METHODS: Specimens taken from human normal liver tissues (group A),
      HBV infected human liver tissues which were HBsAg positive, and HBsAg, anti-HBe,
      and anti-HBc positive in serum (group B) were analysed through the methods of 2
      dimensional electrophoresis (2-DE) and matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS/MS).
      RESULTS: Totally 1125 plus/minus 56 (n=3) spots were detected in the sample of
      group A, 1203 plus/minus 42 (n=3) in group B samples. The percent volume of the
      protein spots was compared to show the proteome alteration in HBV infected human
      liver tissues. Forty proteins were found to present variations of two or more
      than two fold in quantity and 22 differentially expressed protein sports were
      finally identified by MALDI-TOF-MS/MS, including human mitochondrial aldehyde
      dehydrogenase, haptoglobin Hp2, peroxiredoxin 2, etc. CONCLUSION: The protein
      profile of human normal liver tissue and HBV infected liver tissues showed
      obviously difference.

PMID- 18322600
TI  - [Expression of HPV16 L1 protein in insect cell suspension culture system].
AB  - OBJECTIVE: To express the L1 protein of human papillomavirus type 16 (HPV16) in
      insect cell suspension culture system. METHODS: Optimized the conditions of
      suspension culture, recombinant virus amplification and protein expression.
      Determined the virus tilter by plague analysis and detected the target protein by
      SDS-PAGE and Western blot; The formation of VLPs by HPV16 L1 protein was observed
      with TEM. RESULTS: The Sf9 cells could grow better in suspension culture with
      seeding density of 5 x 10-5 cell/mL and the maximum expression quantity was
      obtained by infection of cells with rBacV/HPV16L1 (MOI =10) and harvesting after
      72-84 h. HPV16L1 protein could assemble into VLPs in Sf9 cells observed with TEM.
      CONCLUSION: The conditions of cell culture, virus amplification and protein
      expression were optimized. HPV16 L1 protein could assemble into VLPs in Sf9
      cells, which would provide a foundation for further study of the vaccine and
      diagnosis kits.

PMID- 18322601
TI  - [Concordance between hepatitis C virus serotype and genotype in chronic hepatitis
      C patients in China].
AB  - OBJECTIVE: To investigate the relationship of hepatitis C virus (HCV) serotype
      with genotype. METHODS: The serotypes of HCV in the serum of 104 patients with
      chronic hepatitis C from 14 cities in China for which HCV genotypes were
      available, were determined by ELISA using Murex HCV Serotyping 1-6 Assay.
      RESULTS: The serotypes of 86 (82.69 percent) of the 104 serum specimens were
      determined, and HCV serotypes were determined for 91 strains. Overall the
      concordance between hepatitis C virus serotype and genotype was 62.1 percent, and
      the concordance of serotype, with genotypes 1, 2 and 3 were 69.4 percent, 51.2
      percent and 70.0 percent, respectively. The false-negative rate and concordance
      of genotype 2b was lower (54.5 percent). CONCLUSION: The specificity of HCV
      serotyping was affected by HCV strains' genotype and sometimes HCV serotype was
      not in concordance with genotype.

PMID- 18322602
TI  - [Efficacy and safety of Fufang Biejia Ruangan tablet in patients with chronic
      hepatitis B complicated with hepatic fibrosis].
AB  - OBJECTIVE: To study the clinical therapeutic effects and safety of Fufang Biejia
      Ruangan tablet (FBRt) in patients with chronic hepatitis B complicated with
      hepatic fibrosis. METHODS: Totally 420 patients were randomly divided into two
      groups, FBRt group (300 cases) were treated with Fufang Biejia Ruangan tablets
      and control group (120 cases) were treated with He Luo Shu Gan capsule, the
      patients in both groups were treated for 6 months. RESULTS: The cure rate and
      total effective rate of FBRt group were significantly higher than those of
      control group (55.67 percent and 81.67 percent vs. 15.8 percent and 60.00
      percent, P less than 0.01). CONCLUSION: Fufang Biejia Ruangan tablet could
      alleviate clinical symptoms and hepatic fibrosis. Fufang Biejia Ruangan tablet is
      effective and safe in treatment of patients with chronic hepatitis B complicated
      with liver fibrosis.

PMID- 18322603
TI  - [Detection of serum Th1 and Th2 cytokines and its significance in neonates with
      cytomegalovirus pneumonia].
AB  - OBJECTIVE: To investigate changes in the levels of Th2 cytokine interleukin-4 (IL
      4), Th1 cytokine interferon-gamma (IFN-gamma), and TNF-alpha in serum of newborn
      infants with cytomegalovirus (CMV) pneumonia. METHODS: Twenty-five neonatal cases
      who were positive for serum IgM antibody to CMV by ELISA were divided into IVIG
      intervention group and ganciclovir intervention group, and 15 healthy neonates
      were enrolled into the control group. The levels of IL-4, IFN-gamma, and TNF
      alpha were detected by using double antibody ELISA for the control group and the
      intervention groups at the beginning and end of treatment. RESULTS: The levels of
      IFN-gamma and TNF-alpha in patients with CMV pneumonia were higher than that in
      the healthy neonates, while the levels of IL-4 were lower(t= 2.65 and 3.16, p
      less than 0.05). The level of IL-4 in patients with CMV pneumonia was
      significantly lower than that of the healthy neonates (t= 2.49, p less than
      0.05). There was no significant difference in the levels of IFN-gamma, IL-4 and
      TNF-alpha between IVIG intervention group and ganciclovir intervention group at
      the beginning of treatment (t= 1.85, 1.71, 1.76, p greater than 0.05). In IVIG
      intervention group, the levels of IFN-gamma and TNF-alpha significantly decreased
      after treatment (t=3.98, 5.16, p less than 0.01), the level of IL-4 in this group
      was higher than that before treatment (t= 2.55, p less than 0.05). In ganciclovir
      group, the level of IFN-gamma and TNF-alpha did not change after treatment
      (t=1.75, 1.16, p greater than 0.05), the level of IL-4 in this group was higher
      than that before treatment (t= 2.39, p less than 0.05). CONCLUSION: There seems
      to be an imbalance of Th1 and Th2 cytokines secretion in the infants with CMV
      pneumonia and, which may lead to immune-inflammation injury. IVIG can regulate
      imbalanced Th1/Th2 activities, therefore, immunomodulatory treatment should be
      applied besides antiviral therapy.

PMID- 18322604
TI  - [Effectiveness and safety of bicyclol combined with thymosin in treatment of
      chronic viral hepatitis B].
AB  - OBJECTIVE: To analyze the efficacy and safety of bicyclol combined with thymosin
      in treatment of chronic viral hepatitis B (CHB). METHODS: A total of 135 patients
      with CHB were randomized into experimental group and control group. The patients
      in the experimental group received bicyclol orally 75 mg daily and thymosin 20 mg
      intramuscular injection once every 2 days for 24 weeks and those in control group
      received bicyclol orally 75 mg daily alone for 24 weeks. The levels of serum
      aminotransferase (ALT/AST), HBV-DNA, HBeAg /antiHBe were observed. RESULTS:
      Compared with pre-treatment levels, the serum aminotransferase levels decreased
      significantly in both groups, but there were no statistically significant
      differences between them. HBeAg negative conversion rate was significantly higher
      in the experimental group than in the control group (35.3 percent vs.19.4
      percent, P less than 0.05). HBV DNA negative conversion rate was significantly
      higher in the experimental group than in the control group (36.7 percent vs. 20.9
      percent, P less than 0.05). No obvious adverse events which were probably related
      to the drugs were observed in this study. CONCLUSION: The combination of bicyclol
      with thymosin had better effect in treatment of chronic hepatitis B ias compared
      with bicyvlol alone.

PMID- 18322605
TI  - [Comparison of bicyclol therapy for patients with genotype B and C of hepatitis B
      virus].
AB  - OBJECTIVE: To compare the efficacy of bicyclol tablets on patients infected with
      hepatitis B virus between genotype B and C. METHODS: 70 patients with chronic
      viral hepatitis B were selected. The patients divide into two groups: HBV
      genotypes B (26 cases) and HBV genotypes C (other 44 cases). All patients
      received bicyclol tablets orally 150 mg daily (50mg, tid, po) for 24 weeks. The
      efficacy were observed after 12 weeks and 24 weeks. RESULTS: After treatment for
      24 weeks, the serum aminotransferase were decreased obviously, and HBV DNA levels
      turn to be negative with 19.2 percent (genotype B group) and 15.9 percent
      (genotype C group), respectively. The difference was not statistically
      significant between HBV genotype B and C. CONCLUSION: Bicyclol not only has
      hepatoprotective activity but also inhibited virus replication in patients
      infected with HBV. The difference of the response to bicyclol therapy between HBV
      genotypes B and C was not statistically significant.

PMID- 18322606
TI  - [Effects of Kang Gang Qian Granule (KGQG) on clinical and pathological features
      in chronic hepatitis B patients].
AB  - OBJECTIVE: To explore the efficacy of KGQG and its therapeutic mechanisms in
      chronic hepatitis B patients with liver fibrosis. METHODS: 57 chronic hepatitis B
      patients with liver fibrosis were randomly divided into two groups: 45 cases in
      KGQG group were treated by KGQG and routine medications; 12 cases in control
      group were treated by routine medications only. Serum liver function test
      results, PCIII, CIV, HA and liver biopsy results of these 57 patients were
      simultaneously collected and analyzed before and after this intervention.
      RESULTS: KGQG group showed better efficacy over control group in liver function
      recovery, decrease of serum PCIII, CIV, HA levels and liver pathologic grades (P
      0.05 or 0.01). CONCLUSION: The KGQG could effectively ameliorate liver function
      and facilitate the inhibition and degradation of liver fibrosis in chronic
      hepatitis B patients, which may be developed as a novel therapeusis to treat this
      hard-to-cure disease.

PMID- 18322607
TI  - [Distribution of hepatitis B virus genotypes and its clinical significance].
AB  - OBJECTIVE: To study the distribution of hepatitis B virus genotypes in Handan
      area and clarify the genotype-related difference in clinic. METHODS: Polymerase
      chain reaction-restricted fragment length polymorphism (PCR-RFLP) was used to
      detect the HBV genotypes in 108 HBV-infected patients from Handan area. The
      clinical significance of HBV genotype was analyzed in combination with the values
      of HBV DNA and ALT. RESULTS: Among the 108 HBV-infected patients, the proportion
      of genotype B and C was 6.5 percent and 93.5 percent, respectively. Genotype
      distribution showed no significant difference between male and female patients.
      ALT and AST levels were higher in genotype C group than those in genotype B
      group. CONCLUSION: HBV genotype C is predominant in chronic hepatitis B patients
      in Handan area. The positive rates of HBeAg and HBV DNA levels were higher in
      genotype C group than those in genotype B group. Genotype C was associated with
      the development of severe liver disease as compared to genotype B.

PMID- 18322608
TI  - [Research of hepatic pathology and clinical characteristics of patients chronic
      infected with hepatitis B virus in immune tolerant stage].
AB  - OBJECTIVE: To investigate the characteristics of the hepatic pathological and
      clinical features of patients with hepatitis B virus (HBV) in immune tolerant
      stage and find the better measure of diagnosing patients chronic infected by HBV
      in immune tolerant phase. METHODS: 135 patients with HBV chronic infection and
      persistently normal serum alanine aminotransferase (ALT) levels were involved in
      this study, whose serum HBeAg and HBV DNA were positive. Statistical analysis
      included the ages, sex, serum levels of HBVDNA, ALT and histological grade. The
      grades of inflammation and fibrosis were obtained through hepatic biopsy
      performed on all the patients. RESULTS: Mean age in those patients was 22.61 +/-
      8.95 years old. All those patients were divided into two groups according to
      histological grade: low- histological grade group, G < or = 1 and S < or = 1; and
      high-histological grade group, G > or = 2, S > or = to 2. Levels of histological
      grade were low in most of patients (99/135). Patients of low-histological grade
      had no difference in age, sex and family history of HBsAg carriers. Compared with
      low-normal ALT (ALT less than 30U/L), those with high-normal ALT (ALT > or =
      30U/L) had a greater frequencies of high-histological grade. Compared with high
      HBVDNA (HBVDNA > or = 10(7) copies/ml), those with low HBVDNA (HBVDNA less than
      10(7) copies/ml) had a greater frequencies of high-histological grade.
      CONCLUSION: Levels of histological grade were low in most of patients with HBV
      chronic infection, serum HBeAg and HBVDNA positive, persistently normal serum ALT
      levels, but some of them were high-histological grade. It showed those patients
      were not all in immune tolerant stage of chronic HBV infection. Examination of
      ALT and HBVDNA are helpful to evaluate hepatic pathological damage for them.

PMID- 18322609
TI  - [To re-evaluate the clinical classification criteria of liver failure].
AB  - OBJECTIVE: To study the clinical feature and more reasonable diagnostic typing
      criteria for patients with liver failure. METHODS: 13/21 cases of ALF, SALF with
      no past liver disease, 49/72 cases of with chronic hepatitis, and 23/73 cases
      ALF, SALF with liver cirrhosis, were analyzed respectively. RESULTS: 1 ALF
      patients (1). There exist significant statistic differences in ALB, ALT, CHE in
      three ALF groups.(2). It had statistic differences in those patients with hepatic
      encephalopathy.(3). The prognosis of the patients with chronic hepatitis group
      (42.85 percent) was best than that of chronic cirrhosis (26.09 percent) and no
      past liver disease (15.38 percent). (2) In SALF patients (1). There exist
      significant statistic differences in ALB, GLO, ALT, AST, BDIL, GLU and CHE in
      three SALF groups.(2). It had statistic differences in those patients with
      hepatic encephalopathy in three SALF groups.(3). The prognosis of the patients
      with chronic hepatitis group (51.39 percent) was best than that of chronic
      cirrhosis (36.85 percent) and no past liver disease (33.33 percent). CONCLUSION:
      There are different clinic feature and prognosis in three ALF or SALF groups, so
      we suggest that it were clinic practicability and science in classify of liver
      failure at present.

PMID- 18322610
TI  - [To explore the clinical significance of HBV large protein (HBV-LP) in diagnosing
      viral replication].
AB  - OBJECTIVE: To explore the clinical significance of HBV large protein (HBV-LP) in
      diagnosing viral replication, we detected the HBV-LP, HBV DNA and the hepatitis B
      viral markers (HBV M) in the serum of the patients infected with HBV. METHODS:
      HBV-LP and HBV M were analyzed by using ELISA. HBV-DNA was quantitatively
      detected using real-time fluorescent polymerase chain reaction. RESULTS: (1) No
      significant difference between the detectable rate of HBV DNA and HBV-LP was
      found in the same HBV M (P 0.05). (2) No significant difference between the
      positive rate of HBV DNA and HBV-LP was found in HBeAg negative patients. (3) The
      contents of serum HBV-LP was positively correlated with the number of HBV DNA
      copies. CONCLUSION: There was a close correlation between the positive rate of
      HBV-LP and HBV DNA, and HBV-LP is a reliable serological marker that can reflect
      the replication of HBV.

PMID- 18322611
TI  - [Clinical significance of serum glutamyl transpeptidase in chronic hepatitis B].
AB  - OBJECTIVE: To evaluate the relationship between changes and clinical significance
      of serum glutamyl transpeptidase (GGT) and the degree of liver lesions in chronic
      hepatitis B (CHB). METHODS: Examinations of serum ALT, AST, GGT levels and liver
      biopsy were carried out and classification and staging of liver fibrosis and
      inflammation were performed for 70 patients with CHB. The relationship between
      ALT, AST, GGT and CHB was analyzed. RESULTS: (1) ALT, AST and GGT increased with
      the degree of inflammation and fibrosis, but their levels declined with the
      degree of G4 and S4. The correlation coefficients of ALT and GGT, AST and GGT
      were (0.322 and 0.328, P less than 0.05). With liver-protective treatment, in the
      cases with mild CHB, ALT was normalized quickly but GGT remained at a lower
      level. While ALT declined, GGT was still at a relatively high level for moderate
      and severe CHB cases, among them the level of GGT fluctuated. CONCLUSION: Serum
      GGT reflects the degree of liver inflammation more accurately than ALT and AST do
      and GGT activity can provide important evidence for clinical assessment of
      chronic hepatitis B.

PMID- 18322612
TI  - [Development and evaluation of a double antigen sandwich ELISA for the detection
      of total antibodies against hemorrhagic fever with renal syndrome virus].
AB  - OBJECTIVES: To develop and evaluate a method for detection of the total
      antibodies against hemorrhagic fever with renal syndrome (HFRS) virus with
      improved sensitivity and simplified operation procedure. METHODS: The nucleic
      proteins of hantavirus were used as coating antigens as well as detection
      antigens labeled with horse radish peroxidase (HRP). The operation protocol was
      established, optimized and compared with indirect fluorescence assay (IFA).
      RESULTS: The specificity of this method was 100 percent in the test of different
      human sera and 4-8 times more sensitive than IFA. And, it is simpler without
      requiring any change of the reagents, different sources of samples did not affect
      the results of the test. CONCLUSION: This method is specific, sensitive and
      simple for detection of the total antibodies in sera against hantavirus, could be
      used for the screening of Hantavirus infection in human and host rodent animals.

PMID- 18322613
TI  - [Evaluation on the use of detection of hepatitis C core antigen for screening
      blood donor].
AB  - OBJECTIVE: To investigate the value of detection of hepatitis C virus core
      antigen (HCV-cAg) for screening blood donor by using the internal reagent enzyme
      immunoassay (EIA) and anti-HCV antibody. METHODS: The first and repeat assays
      were performed for detection of serum anti-HCV and HCV-cAg ELISA in 3972 donor's
      serum specimens from August to October of 2004. Twenty-five donors positive for
      anti-HCV were tested with HCV-cAg EIA kits and the results were compared with the
      results of HCV RNA determination with RT-PCR method. RESULTS: In 3972 donor's
      serum samples, only 1 serum specimen was positive for HCV RNA identification
      among 10 specimens which were positive for anti-HCV in first assays, and only 1
      serum specimens was positive for HCV RNA identification among 12 specimens
      positive for anti-HCV in repeat assays, only 2 serum specimens were positive HCV
      RNA identification in 3 specimens which were positive for HCV-cAg assays.
      CONCLUSION: The sensitivity of HCV-cAg ELISA is similar to HCV RT-PCR, but it is
      much cheaper. Therefore, HCV-cAg ELISA and anti-HCV may be used together to
      screen blood donor.

PMID- 18322614
TI  - [Establishment and evaluation of the diagnostic kit for anti-HIV1/2 antibody and
      P24 antigen].
AB  - OBJECTIVE: To establish and evaluate an Enzyme Immunoassay diagnostic kit
      combined with anti-HIV1/2 antibody and P24 antigen for shortening the examination
      window period of HIV infection in HIV laboratory diagnosis. METHODS: The enzyme
      linked reaction plates was coated by anti-HIV P24 monoclonal antibody and HIV 1/2
      antigen. Labeling HIV1/2 antigen and anti-HIV P24 polyclonal antibody with
      horseradish peroxidase, setup an integrated ELISA kit for detecting anti-HIV-1/2
      antibody and HIV P24 antigen, and evaluate the specificity and sensitivity of
      this kit. RESULTS: The sensitivity of testing P24 antigen was up to 0.2 ng/ml. 78
      serum samples of patients with AIDS, 85 serum samples of healthy people were
      compared with Abbott EIA kit, the coincidence was 100%. 12 051 sera from normal
      persons and patients were examined, the sensitivity of 100 %and specificity of
      99.62 %, respectively. CONCLUSION: The anti-HIV1/2 antibody and HIV P24 antigen
      can be measured at the same time using this EIA kit, while the examination window
      period of HIV infection is shortened. Thus, the method is suitable for laboratory
      diagnosis and epidemiological investigation.

PMID- 18322615
TI  - Doubly bonded systems between heavier Group 15 elements.
AB  - There has been much interest in the synthesis and properties of doubly bonded
      systems between heavier Group 15 elements, i. e. heavier analogues of azo
      compounds (dipnictenes), from the viewpoints of fundamental and material
      chemistry. Although such double-bond compounds between heavier main group
      elements are known to be highly reactive, too much so to be isolated as stable
      compounds, a number of reports on the synthesis of kinetically stabilized
      diphosphenes (RP[double bond, length as m-dash]PR), diarsenes (RAs[double bond,
      length as m-dash]AsR), and phosphaarsenes (RP[double bond, length as m-dash]AsR)
      bearing bulky substituent have been published since 1980. We have also succeeded
      in the synthesis of the first stable distibene (RSb[double bond, length as m
      dash]SbR) and dibismuthene (RBi[double bond, length as m-dash]BiR) by taking
      advantage of efficient steric protection groups, 2,4,6
      tris[bis(trimethylsilyl)methyl]phenyl (Tbt) and 2,6
      bis[bis(trimethylsilyl)methyl]-4-[tris(trimethylsilyl)methyl]phenyl (Bbt), and
      revealed their structures and properties systematically. Thus, the doubly bonded
      compounds between heavier Group 15 elements are no longer imaginary species but
      are those with real existence which are stable, even in the case of the heaviest
      non-radioactive element bismuth, when they are appropriately protected by bulky
      substituents. This Perspective describes our research on the chemistry of
      kinetically stabilized double-bond compounds between heavier Group 15 elements.

PMID- 18322616
TI  - A simple entry into nido-C2B10 clusters: HCl promoted cleavage of the C-C bond in
      ortho-carboranyl diphosphines.
AB  - Treatment of the diphosphines ortho-B10H10C(P(t)Bu2)C(PR2) (R = Et, Cy, Ph) with
      HCl gives the zwitterionic, nido-12-vertex species B10H10C(PH(t)Bu2)C(PClR2);
      these reactions are reversed by the addition of NEt3.

PMID- 18322617
TI  - Platinum(II) Schiff base as versatile phosphorescent core component in conjugated
      oligo(phenylene-ethynylene)s.
AB  - Novel phosphorescent conjugated oligo(phenylene-ethynylene)s featuring a central
      tunable platinum(II) Schiff base signalling unit with promising photophysical
      properties have been investigated to pave their development towards polymeric
      congeners for sensing applications.

PMID- 18322618
TI  - Isolation of extendable transition metal incorporated polyoxometalate
      intermediates with structural control.
AB  - Three discrete cobalt-substituted silicotungstates, [Co3(H2O)(B-beta-SiW9O34)(B
      beta-SiW8O29(OH)2)]12- (1), [Co3(H2O)(B-alpha-SiW9O34)(B-beta-SiW8O31)]14- (2),
      and [Co9Cl2(OH)3(H2O)9(B-beta-SiW8O31)3]17- (3), have been synthesized using a
      synthetic approach involving Co(II) ions, the dilacunary [gamma-SiW10O36]8-
      polyanion and a bulky organic cation in basic media; all three compounds have
      been fully characterized and their position as structural intermediates in Co
      containing silicotungstate chemistry is described.

PMID- 18322619
TI  - Formation of monometallic single-molecule magnets with an Stotal value of 3/2 in
      diluted frozen solution.
AB  - A combination of cobalt(II) complexes and pyridine ligands carrying organic
      spins, aminoxyl and carbene, provided single-molecule magnets with Stotal = 3/2
      in diluted frozen solutions.

PMID- 18322620
TI  - Relationships between Hg(II)-S bond distance and Hg(II) coordination in
      thiolates.
AB  - Extended X-ray absorption fine structure (EXAFS) spectroscopy is a sensitive
      structural probe of the coordination environments of Hg(II) with thiol
      (sulfhydryl) groups, and is equally applicable to solid and aqueous organic or
      inorganic matter. Information on the number and geometric arrangement of S
      ligands can be derived from metal-ligand distances because the distances vary
      with Hg stereochemistry and can be accurately measured by the EXAFS technique. To
      improve the reliability of determining coordination structures of Hg with thiol
      groups, correlations among Hg-S bond distance, Hg coordination, and S-Hg-S angle
      in homoleptic Hg(II)-thiolates were calculated from analysis of the structures of
      the 162 Hg(SR)n motifs (n = 2, 3, 4) contained in the Cambridge Structural
      Database v. 5.28. Graphical correlations of bond distance with coordination
      number and with bond angle show distinct ranges of values characteristic of
      specific structural configurations.

PMID- 18322621
TI  - Effects of molybdenum substitution on the photocatalytic behavior of BiVO4.
AB  - Transition metal doping has always suffered from the disadvantage of reduction of
      photocatalytic activity because the dopant ions can form a discrete level in the
      forbidden band of the photocatalyst resulting in low mobility of electrons and
      holes in the dopant level and thus lowered activity. However, in this study the
      photocatalytic activity of an efficient visible-light sensitive photocatalyst,
      BiVO4, for water oxidation or organic compound degradation was found to be
      remarkably enhanced by molybdenum doping. The role of molybdenum doping in
      enhancing the photocatalytic activity of BiVO4 was investigated and discussed
      based on the changes of the surface acidity of the photocatalyst.

PMID- 18322622
TI  - Structural, magnetic, high-frequency and high-field EPR investigation of double
      stranded heterometallic [{Ni(en)2}2(micro-NCS)4Cd(NCS)2](n).nCH3CN polymer self
      assembled from cadmium oxide, nickel thiocyanate and ethylenediamine.
AB  - A novel heterometallic 1D coordination polymer [{Ni(en)2}2(micro
      NCS)4Cd(NCS)2](n) x nCH3CN (en = ethylenediamine) has been prepared using the
      self-assembly process in a one-pot reaction of cadmium oxide, nickel and ammonium
      thiocyanates with an acetonitrile solution of ethylenediamine. The complex
      consists of an uncommon cis-Cd(SCN)4(NCS)2(4-) fragment and a rare combination of
      cis-Ni(en)2(2+) and trans-Ni(en)2(2+) building blocks linked by micro(1,3)-NCS
      bridges into a double-stranded zigzag chain structure. Each chain is comprised of
      [Ni2Cd2(micro-NCS-N,S)4)] macrocycles with chair-like and rectangular-like shapes
      arrayed alternately. The shortest intrachain CdCd separations are 9.535(1) and
      10.868(2) A, while the nearest NiNi distances are 5.418(1) and 6.612(2) A. A
      network of weak N-HS hydrogen bonds, involving the terminal NCS ligands and NH2
      groups of en, links the infinite chains and results in the formation of an
      extended supramolecular three-dimensional framework. Variable-temperature (1.8
      300 K) magnetic susceptibilities show a slight change of the micro(B) value at
      low temperature, indicative of weak antiferromagnetic interactions (J = 1.55 cm
      1) between magnetic canters. High-field, high-frequency (100-400 GHz) EPR spectra
      were simulated using S = 1 ground state for separate Ni2+ ions with the spin
      Hamiltonian parameters g = 2.165, D = 0.45 cm-1 and E = 0.03 cm(-1). According to
      DFT calculations, the D and E parameters are -0.35 cm(-1) and 0.049 cm-1 for the
      cis arrangement of Ni2+ and 0.58 cm(-1) and 0.012 cm(-1) for trans.

PMID- 18322623
TI  - Robust chiral zirconium alkoxide initiators for the room-temperature
      stereoselective ring-opening polymerisation of rac-lactide.
AB  - Chiral Schiff bases (1H to 4H) and a series of their Group 4 metal alkoxide
      complexes [(R-1)2Ti(O(i)Pr)2, (R-2)2Ti(O(i)Pr)2, (R-1)(2)Zr(O(i)Pr)2, (R
      2)2Zr(O(i)Pr)2, (R-3)2Zr(O(i)Pr)2, (R-4)2Zr(O(i)Pr)2, (S-1)2Zr(O(i)Pr)2 and (rac
      1)2Zr(O(i)Pr)2] have been prepared and characterised by 1H, and 13C NMR
      spectroscopy. In solution, both Lambda and Delta isomers were observed,
      suggesting a low degree of chiral induction from the ligand. One ligand (R-4H)
      and three complexes [Delta-(R,R-2)2Ti(O(i)Pr)2, Lambda-(R,R-1)2Zr(O(i)Pr)2 and
      Delta-(R,R-3)2Zr(O(i)Pr)2] have also been characterised by single crystal X-ray
      diffraction. All complexes were found to have a pseudo-octahedral alpha-cis
      geometry. The complexes were tested as initiators for the ring-opening
      polymerisation of rac-lactide in solution and in the melt. The titanium complexes
      are inactive in solution and afford atactic polylactide in the melt. Zr(iv)
      complexes afford heterotactically enriched polylactide both in toluene solution
      (at 20 degrees C and 80 degrees C) and in the melt. Polymerisations were
      generally found to be well-controlled, giving predictable molecular weights and
      low molecular weight distributions. Ligand variation (substituents and/or
      chirality) has little effect on either the activity or selectivity of initiators.
      Zirconium initiators were found to be unusually robust as they were able to
      maintain well-controlled polymerisation following addition of water to reactions
      in solution and when using unpurified monomer for reactions in the melt.

PMID- 18322624
TI  - Mononuclear, dinuclear, hexanuclear, and one-dimensional polymeric silver
      complexes having ligand-supported and unsupported argentophilic interactions
      stabilized by pincer-like 2,6-bis(5-pyrazolyl)pyridine ligands.
AB  - The mononuclear complexes [Ag(H2L1)(Py)2](NO3) x H2O (1, H2L1 = 2,6-bis(5-methyl
      1H-pyrazol-3-yl)pyridine) and [Ag(NO3)(L()] (2, L2 = 2,6-bis(5-methyl-1-isopropyl
      1H-pyrazol-3-yl)pyridine), dinuclear complex [Ag2(H2L3)2(HL4)2] (3, H2L3 = 2,6
      bis(5-phenyl-1H-pyrazol-3-yl)pyridine, HL4 = 6-(5-phenyl-1H-pyrazolyl-3
      yl)picolinate), one-dimensional polymer {[Ag2(H2L1)2](NO3)2 x H2O}(n) (4), and
      hexanuclear clusters [Ag6(HL1)4](X)2 (X = NO3-, 5 ; BF4-, 6 ; ClO4-, 7)
      stabilized by pincer-like bispyrazolyl ligands have been prepared and
      characterized using (1)H NMR spectroscopy, elemental analysis, IR spectroscopy,
      luminescence spectroscopy and X-ray diffraction. In complex , there is a ligand
      unsupported Ag-Ag bond between the two silver atoms. Complex displays a one
      dimensional polymer consisting of an infinite Ag-Ag chain and every two adjacent
      silver ions are bridged by an H2L1 ligand. Complexes and have the same Ag6 cores
      in which six silver atoms are held together by four HL1 and five Ag-Ag bonds,
      while complex was held together by six Ag-Ag bonds. The silver-silver distances
      in these complexes are found in the range of 2.874(1)-3.333(2) A for ligand
      supported, and 3.040(1) A for ligand unsupported Ag-Ag bonds, respectively.
      Complexes 3-7 are strongly luminescent due to either intraligand or metal-ligand
      charge transfer processes.

PMID- 18322625
TI  - Synthesis, structure, and reactivity of Group 4 metallacycles incorporating a
      Me2C-linked cyclopentadienyl-carboranyl ligand.
AB  - Group 4 metallacycles [eta5:sigma-Me2C(C5H4)(C2B10H10)]Ti[eta2-N(Me)CH2CH2N(Me)]
      (1a), [eta5:sigma-Me2C(C5H4)(C2B10H10)]Zr[eta2-N(Me)CH2CH2N(Me)](HNMe2) (1b) and
      [eta5:sigma-Me2C(C5H4)(C2B10H10)]M[eta2-N(Me)CH2CH2CH2N(Me)] (M = Ti (2a), Zr
      (2b), Hf (2c)) were synthesized by reaction of [eta5:sigma
      Me2C(C5H4)(C2B10H10)]M(NMe2)(2) (M = Ti, Zr, Hf) with MeNH(CH2)(n)NHMe (n = 2,
      3). These metal complexes reacted with unsaturated molecules such as 2,6
      Me2C6H3NC, PhNCO and PhCN to give exclusively M-N bond insertion products. The M
      C(cage) bond remained intact. Such a preference of M-N over M-C(cage) insertion
      is suggested to most likely be governed by steric factors, and the mobility of
      the migratory groups plays no obvious role in the reactions. This work also shows
      that the insertion of unsaturated molecules into the metallacycles is a useful
      and effective method for the construction of very large ring systems.

PMID- 18322626
TI  - Comparative studies of geometric and quasielastic characteristics of PP and SS
      bonds.
AB  - It is demonstrated that density functional theory in B3PW91/aug-cc-pVTZ
      formulation provides a reasonable estimate of the geometrical and vibrational
      parameters of various PP and SS bonds. Calculated quasielastic characteristics of
      SS bonds, such as relaxed force constants f(SS), are approximately twice as large
      as f(PP). This means much higher elasticity of the PP bond, compared to the SS
      bond. From the dependence of the relaxed force constants on the formal bond
      order, the various PP bonds studied represent single bonds. By contrast, the more
      than twice as high rigidity of the SS bonds implies multiple SS bonding.
      Pronounced shortening of the SS bond on passing from less electronegative to more
      electonegative substituents at the sulfur atoms can be ascribed to the
      corresponding increase of the SS pi interactions. Essentially single PP bonds are
      not affected by electronic effects of this kind, which is the reason for the
      small variability of PP bond lengths in the gas phase. At the same time,
      intermolecular forces acting in crystals may strongly influence the length of
      highly elastic PP bonds.

PMID- 18322627
TI  - Influence of the solvent and R groups on the structure of (carboranyl)R2PI2
      compounds in solution. Crystal structure of the first iodophosphonium salt
      incorporating the anion [7,8-nido-C2B9H10]-.
AB  - The influence of the electron-donor or electron-acceptor capacity of the R groups
      (R = (i)Pr, Ph, Et) and the solvent on the molecular geometry in solution of
      adducts of carboranylphosphanes [(carboranyl)(i)Pr2P, (carboranyl)Ph2P and
      (carboranyl)Et2P] with I2 in 1 : 1 ratios, has been studied in detail by 31P{1H}
      and 11B{1H} NMR spectroscopies. The more electron-accepting Ph groups make the
      (carboranyl)Ph2P less nucleophilic, thus stabilizing the I2 encapsulated neutral
      biscarboranylphosphane-diiodine adducts in solution, such as (carboranyl)Ph2PI
      IPPh2(carboranyl), generating P---I-I---P motifs. Even in a polar solvent, such
      as EtOH, the arrangement is preserved. The expected basicity of these
      carboranylphosphanes is: (carboranyl)(i)Pr2P > (carboranyl)Et2P >
      (carboranyl)Ph2P. Thus, the comparatively higher basicity of (carboranyl)Et2P vs.
      (carboranyl)Ph(2)P facilitates a higher transfer of electron density to the I2
      sigma*, generating the ionic species, [(carboranyl)Et2PI]+I-, even in low polar
      solvents, such as CH2Cl2 and toluene, with no degradation of the cluster.
      However, in EtOH, the formation of the anionic [7,8-nido-C2B(9)H10]- cluster
      takes place by removal of one boron atom from the closo cluster. The basicity of
      (carboranyl)(i)Pr(2)P should be the highest, superior to (carboranyl)Et2P. This
      is observed in the reaction of these carboranylphosphanes with I(2) in EtOH.
      Whereas the formation of P four-coordinated molecular "spoke" charge-transfer
      complexes, (carboranyl)(i)Pr2P-I-I, are suggested for (carboranyl)(i)Pr2P in low
      polarity solvents, ionic species are formed in ethanolic solutions, which
      deboronate in a few days, faster than (carboranyl)Et2P, to yield the zwitterionic
      species. This is attributed to the higher basicity of (carboranyl)(i)Pr2P vs.
      (carboranyl)Et2P. The X-ray crystal structure of [7-PI(i)Pr2-8-Ph-7,8-nido
      C2B9H10], 2c, obtained from the reaction of 1-P(i)Pr2-2-Ph-closo-1,2-closo
      C2B10H10 with I(2) in EtOH, confirms the formation of the zwitterion. These
      results prove that minor changes in the nature of the R substituents on the P
      atom in carboranylphosphanes, along with the solvent in which the reaction takes
      place, produce major alterations in the geometry of the (carboranyl)R2P-I-I
      species in solution, and in their possible further reactivity.

PMID- 18322628
TI  - Synthesis and characterisation of new bimetallic alkali metal-magnesium mixed
      diisopropylamide-acetylides: structural variations in bimetallic lithium- and
      sodium-heteroleptic magnesiates.
AB  - The reactivity of the Bronsted basic mixed-metal tris-amide compounds of
      empirical formula [MMg(N(i)Pr2)3] [where M = Li (1), Na (2)] towards
      phenylacetylene (HC[triple bond, length as m-dash]CPh) has been investigated and
      has led to the synthesis of a series of mixed-metal acetylido-amido-magnesiates.
      Thus, 1 and 2 molar equivalents of the alkyne with [MMg(N(i)Pr2)3] produce
      heteroanionic bis(amido)-mono(acetylido) [LiMg(N(i)Pr2)2(C[triple bond, length as
      m-dash]CPh)]2 (3) and mono(amido)-bis(acetylido) [(TMEDA) x Na(C[triple bond,
      length as m-dash]CPh)2Mg(N(i)Pr2)](2) (4) (TMEDA = N,N,N',N'
      tetramethylethylenediamine) respectively. X-Ray crystallographic studies reveal
      that the new compounds adopt a different structural motif. Complex can be defined
      as an inverse crown structure, having a cationic eight-atom [(NaNMgN)2]2+ ring
      which hosts in its core two acetylido ligands. On the other hand, adopts a
      tetranuclear NaMgMgNa near-linear chain arrangement, held together by acetylido
      and amido bridges. The metal coordination geometries in both structures are
      distorted tetrahedral, and the sodium cations at the end of the mixed-metal chain
      carry terminal chelating TMEDA ligands. 1H and 13C NMR spectral data recorded in
      C6D6 solutions are also reported for and , and are consistent with the solid
      state structures being retained in solution.

PMID- 18322629
TI  - Synthesis and characterization of ZnO and ZnO:Ga films and their application in
      dye-sensitized solar cells.
AB  - Highly crystalline ZnO and Ga-modified zinc oxide (ZnO:Ga) nanoparticles
      containing 1, 3 and 5 atom% of Ga3+ were prepared by precipitation method at low
      temperature. The films were characterized by XRD, BET, XPS and SEM. No evidence
      of zinc gallate formation (ZnGa2O4), even in the samples containing 5 atom% of
      gallium, was detected by XRD. XPS data revealed that Ga is present into the ZnO
      matrix as Ga3+, according to the characteristic binding energies. The particle
      size decreased as the gallium level was increased as observed by SEM, which might
      be related to a faster hydrolysis reaction rate. The smaller particle size
      provided films with higher porosity and surface area, enabling a higher dye
      loading. When these films were applied to dye-sensitized solar cells (DSSCs) as
      photoelectrodes, the device based on ZnO:Ga 5 atom% presented an overall
      conversion efficiency of 6% (at 10 mW cm(-2)), a three-fold increase compared to
      the ZnO-based DSSCs under the same conditions. To our knowledge, this is one of
      the highest efficiencies reported so far for ZnO-based DSSCs. Transient
      absorption (TAS) study of the photoinduced dynamics of dye-sensitized ZnO:Ga
      films showed that the higher the gallium content, the higher the amount of dye
      cation formed, while no significant change on the recombination dynamics was
      observed. The study indicates that Ga-modification of nanocrystalline ZnO leads
      to an improvement of photocurrent and overall efficiency in the corresponding
      device.

PMID- 18322630
TI  - Syntheses, characterization and redox properties of oxo-centred triruthenium
      cluster dimers and trimers linked by ortho-metallated polypyridyl ligands.
AB  - A series of mono-, di- and trimeric oxo-centred triruthenium cluster compounds
      with ortho-metallated polypyridyl ligands were prepared by reaction of oxo
      centred triruthenium precursor compound [Ru3O(OAc)6(py)2(CH3OH)]+ (1) with
      bis(2,2'-bipyridin-5-yl)butadiyne (bpyC[triple bond, length as m-dash]C-C[triple
      bond, length as m-dash]Cbpy), bis(2,2'-bipridin-5-yl)ethyne (bpyC[triple bond,
      length as m-dash]Cbpy), 2,2'-bipyrazine (bpz), pyrazino[2,3-f]quinoxaline (pyq),
      or 4,7-phenanthroline (4,7-phen). As revealed by redox wave splitting, electronic
      interactions are operating between two Ru3O redox centres in most of the
      triruthenium cluster dimers and trimers. The cluster-cluster interactions are
      highly sensitive to the variations in bonding modes of the polypyridyl ligands.
      Ortho-metallation of the bridging ligand induces an enhanced electronic
      interaction between two triruthenium centres.

PMID- 18322631
TI  - Synthesis of aluminium borate-boron oxide and binary titanium-boron and zirconium
      boron oxides from metal alkoxides and (MeO)3B3O3 in non-aqueous solvents.
AB  - The reaction of metal alkoxides M(OR)4 (M = Ti, Zr; R = organyl) with (MeO)3B3O3
      (1 : 0.67) in dry propan-2-one at room temperature led to gels which when dried
      and calcined in air for 24 h at 500-1000 degrees C afforded bi-phased mixed-oxide
      materials formulated as 4TiO2 x 3B2O3 and ZrO2 x B2O3 in high ceramic yields and
      purity; the B2O3 phases of these materials were amorphous. The materials remained
      amorphous upon calcination at lower temperatures. The TiO2 phase of the 4TiO2 x
      3B2O3 was crystalline when calcined at higher temperatures with either anatase
      (600 degrees C) or rutile (>800 degrees C) being obtained. The ZrO2 phase of the
      ZrO2 x B2O3 was crystalline when calcined at higher temperatures and was obtained
      as a metastable tetragonal phase (<700 degrees C) or baddeleylite (>800 degrees
      C). In a similar reaction, Al(O(i)Pr)3 (2 : 1) gave a bi-phased aluminium borate
      boron oxide (Al18B4O(33).7B2O3) after calcination at >700 degrees C. The dried
      gels and oxide materials were all characterized by elemental analysis, TGA-DSC,
      and powder XRD.

PMID- 18322632
TI  - Systems for the management of respiratory disease in primary care - an
      international series: Australia.
AB  - INTRODUCTION: Australia has a complex health system with policy and funding
      responsibilities divided across federal and state/territory boundaries and
      service provision split between public and private providers. General practice is
      largely funded through the federal government. Other primary health care services
      are provided by state/territory public entities and private allied health
      practitioners. Indigenous health services are specifically funded by the federal
      government through a series of Aboriginal Community Controlled Organisations.
      NATIONAL POLICY AND MODELS: The dominant primary health care model is federally
      funded private "small business" general practices. Medicare reimbursement items
      have incrementally changed over the last decade to include increasing support for
      chronic disease care with both generic and disease specific items as incentives.
      Asthma has received a large amount of national policy attention. Other
      respiratory diseases have not had similar policy emphasis. EPIDEMIOLOGY:
      Australia has a high prevalence of asthma. Respiratory-related encounters in
      general practice, including acute and chronic respiratory illness and influenza
      immunisations, account for 20.6% of general practice activity. Lung cancer is a
      rare disease in general practice. Tuberculosis is uncommon and most often found
      in people born outside of Australia. Aboriginal and Torres Strait Islanders have
      higher rates of asthma, smoking and tuberculosis. ACCESS TO CARE: Access to care
      is positively influenced by substantial public funding underpinning both the
      private and public sectors through Medicare. Access to general practice care is
      negatively influenced by workforce shortages, the ongoing demands of acute care,
      and the incremental way in which system redesign is occurring in general
      practice. FACILITIES AVAILABLE: Most general practice operates from privately
      owned rooms. The Australian Government requires general practice facilities to be
      accredited against certain standards in order for the practice to receive income
      from a number of government programs. These standards require GPs to have ready
      access to spirometry, but do not require every practice to have a spirometer.
      FUTURE: The initial assessment and management of acute respiratory illnesses
      currently seen in primary health care settings will continue, but for this to
      occur the sector may have to adapt traditional workforce roles because of
      workforce shortages. In the longer term, climate change and migration patterns
      may result in changes in the epidemiology of regions and populations. The health
      system will continue to reform incrementally in order to deliver improved chronic
      disease care, including care of people with asthma and COPD. The incoming Labor
      Government's National Primary Health Care Strategy provides the high level policy
      opportunity to drive reform. CONCLUSIONS: Australia's complex primary health care
      system is incrementally changing from one of exclusive acute- and episodic-care
      orientation in both the public and private sectors to a system that delivers
      effective anticipatory chronic disease care as well. From a national policy
      perspective, asthma has received most attention. COPD and possibly other
      respiratory diseases may now receive focus.

PMID- 18322633
TI  - Does continuous use of inhaled corticosteroids improve outcomes in mild asthma? A
      double-blind randomised controlled trial.
AB  - AIM: To compare the effects of fluticasone and placebo on asthma control in
      patients with mild asthma. METHOD: Adults with FEV1 >80% predicted and reliever
      use <or=2 times/week were randomised to receive fluticasone 250 mcg/day or
      placebo double-blind for 11 months. Exacerbations were treated with four weeks'
      fluticasone 500 mcg/day. Primary outcomes were electronically-recorded morning
      PEF and FEV1, analysed by mixed model regression. RESULTS: 44 subjects were
      randomised (23-fluticasone, 21-placebo). Fluticasone led to significantly better
      morning FEV1 (mean difference 5.4% predicted, p<0.0001), morning PEF, clinic
      spirometry, exhaled nitric oxide levels, and airway hyperresponsiveness, but
      there were no differences in reliever use, symptoms or quality of life. Fewer
      patients had mild exacerbations on fluticasone (22% vs 62%, p=0.02). CONCLUSION:
      The goals of asthma treatment include not only control of symptoms, but also
      prevention of future adverse outcomes such as exacerbations - which can occur
      even in mild asthma. This study showed that treatment with low dose inhaled
      corticosteroids led to significant improvements in lung function, exacerbations,
      and in pathophysiological predictors of future risk, even though symptoms were
      minimal at entry. For patients with mild asthma, discussion about treatment needs
      to consider not only short-term benefit, side effects and cost, but also long
      term reduction of risk. This study was completed prior to mandatory registration
      for clinical trials.

PMID- 18322634
TI  - Analysis of Acropora muricata calmodulin (CaM) indicates that scleractinian
      corals possess the ancestral exon/intron organization of the eumetazoan CaM gene.
AB  - Calmodulin (CaM), belonging to the tropinin C (TnC) superfamily, is one of the
      calcium-binding proteins that are highly conserved in their protein and gene
      structure. Based on the structure comparison among published vertebrate and
      invertebrate CaM, it is proposed that the ancestral form of eumetazoan CaM genes
      should have five exons and four introns (four-intron hypothesis). In this study,
      we determined the gene structure of CaM in the coral Acropora muricata, an
      anthozoan cnidarian representing the basal position in animal evolution. A CaM
      clone was isolated from a cDNA library constructed from the spawned eggs of A.
      muricata. This clone was composed of 908 nucleotides, including 162 base pairs
      (bp) of 5'-untranslated region (UTR), 296 bp of 3'-UTR, and an open reading frame
      450 bp in length. The deduced amino acid indicated that the Acropora CaM protein
      is identical to that of the actiniarian, Metridinium senile, and has four
      putative calcium-binding domains highly similar to those of other vertebrate or
      invertebrate CaMs. Southern blot analysis revealed that Acropora CaM is a
      putative single-copy gene in the nuclear genome. Genomic sequencing showed that
      Acropora CaM was composed of five exons and four introns, with intron II not
      corresponding to any region in the actiniarian CaM gene, which possesses only
      four exons and three introns. Our results highlight that the coral CaM gene
      isolated from A. muricata has four introns at the predicted positions of the
      early metazoan CaM gene organization, providing the first evidence from the basal
      eumetazoan phylum to support the four-intron hypothesis.

PMID- 18322635
TI  - Evolution of exceptionally large genes in prokaryotes.
AB  - Analysis of bacterial genomic sequences revealed an average bacterial gene size
      of approximately 1 kb. However, genes with a size >10 kb were also noted. This
      study investigates the prevalence, possible function, and origin of exceptionally
      large-size genes (ELSGs; >10 kb) in prokaryotes. Forty-two ELSGs (0.03%) were
      identified after searching more than 170,000 genes in 46 bacterial and 11
      archaeal species. These ELSGs were found in diverse species including both
      archaeal and eubacterial kingdoms. Homology analysis of these ELSGs indicates
      that, other than encoding nonribosomal peptide synthesis enzymes, many ELSGs
      likely encode cell surface proteins. The ELSGs have different degrees of codon
      usage bias, and evidence of gene expression is observed in some cases. Both
      intragenic domain duplication and gene recombination are major means contributing
      to gene size expansion in these ELSGs. Direct evidence of gene fusion was
      identified in only one ELSG. Finally, several ELSGs showed recent horizontal
      transfer signatures. In summary, ELSGs are commonly present in prokaryotes. Aside
      from their large size, the evolutionary process of ELSGs is quite heterogeneous.

PMID- 18322636
TI  - AFFECT: a prospective, open-label, multicenter trial to evaluate the feasibility
      and safety of a short-term treatment with subcutaneous certoparin in patients
      with persistent non-valvular atrial fibrillation.
AB  - BACKGROUND: Patients with persistent atrial fibrillation (AF) scheduled for
      electrical cardioversion need immediate anticoagulation. Unfractionated heparin
      (UFH) is often used for early anticoagulation in these patients before oral
      anticoagulation becomes effective. However, dose adjustment is required to
      achieve a two- to three-fold prolongation of the activated partial
      thromboplastin. Low molecular weight heparins, given in body weight-adjusted or
      independent fixed dosage, require less laboratory monitoring and are also
      effective within hours of first dosing. They seem to be an attractive alternative
      to UFH. Previous evidence has shown that these drugs are safe and effective in
      this indication. PATIENTS AND METHODS: In this prospective, open-label,
      multicenter pilot study, 203 patients were enrolled with persistent non-valvular
      AF scheduled for electrical cardioversion. Patients received a fixed dose of 8000
      U anti-Xa certoparin twice daily starting immediately after enrolment and before
      cardioversion was performed. Patients with AF > 48 h underwent transoesophageal
      echocardiography (TEE) before cardioversion to exclude intra-atrial thrombi.
      After cardioversion, overlapping oral anticoagulation was started. Treatment with
      certoparin was stopped only after two consecutive days with INR values >2.
      OBJECTIVES: The objective was to document the feasibility and safety of a short
      term treatment with a fixed, body weight-independent certoparin regimen (2 x 8000
      U anti-Xa). RESULTS: Out of 203 patients enrolled, 200 received at least one dose
      of certoparin and were included in the analysis (safety population). Median
      treatment duration with certoparin was 7 days. Bleedings were observed in 8
      patients (4.0%) and were classified as major (1.5%) or minor (2.5%). Cerebral
      ischemia was reported for 1 patient (0.5%). One patient showed mild
      thrombocytopenia (0.5%). There were no reports of venous thromboembolism or death
      during the treatment period. CONCLUSION: Certoparin administered at 8000 U anti
      Xa twice daily independent of body weight was safe and appeared to be effective
      in patients with non-valvular AF undergoing electrical cardioversion. Its ease of
      use and the possibility of treatment on an outpatient basis make it an attractive
      option for early anticoagulation in AF.

PMID- 18322637
TI  - Evidence-based systematic review on the efficacy and safety of botulinum toxin-A
      therapy in post-stroke spasticity.
AB  - BACKGROUND: Botulinum toxin type A (BoNTA) has been suggested as an effective
      anti-spastic drug. In this article, we summarized the data of randomized, placebo
      controlled, double- blind trials and conducted a meta-analysis to assess if BoNTA
      is an adequate treatment for spasticity following stroke. OBJECTIVES: To evaluate
      the relevant literature and assess the effectiveness and safety of BoNTA in (1)
      reducing spasticity based on mean change in the Modified Ashworth Scale (MAS) for
      upper and lower limb spasticity from baseline; (2) reducing spasticity based on
      the percent of patients having > or = 1point(s) change in the MAS; (3) improving
      the patient's or caregivers' Global Assessment Scale (GAS); and (4) total adverse
      events. METHOD: We selected all randomized, placebo controlled, double-blind
      clinical trials or previous meta-analyses evaluating the efficacy and safety of
      BoNTA (Botox or Dysport) for the treatment of spasticity in both upper and lower
      limbs after stroke. Validity assessment of studies was performed, and Revman
      4.2.7 from Cochrane Collaboration and SPSS (statistical package for the social
      sciences), v 9.0, were applied for analysis. RESULTS: Overall analysis showed
      clinical improvement between baseline and 4-6 weeks after application of BoNTA of
      the patient's spasticity score using the MAS (weighted mean difference [WMD] =
      0.87, 95% CI = 0.52-1.22). The odds ratio of the MAS spasticity score showing one
      or more points improvement at 4-6 weeks after giving BoNTA showed clinically
      significant improvement (OR = 4.5, 95% CI = 2.79-7.25). The odds ratio of having
      an improved GAS at 4-6 weeks after injecting BoNTA showed clinically significant
      improvement (Odds ratio = 5.85, 95% CI = 3.12-10.95). The odds ratio of having an
      adverse event during the entire study did not show any significant difference
      between placebo and BoNTA (odds ratio = 0.84, 95% CI = 0.55-1.28). REVIEWERS'
      CONCLUSIONS: BoNTA improves muscle tone in upper and lower limb spasticity
      following stroke. A global assessment of improvement was noted by the patients or
      the caregivers following BoNTA injection. BoNTA is considered a safe therapeutic
      agent.

PMID- 18322638
TI  - Evidence for the effectiveness of botulinum toxin for writer's cramp.
AB  - We performed a comprehensive literature search of clinical studies published
      between 1989 and 2007 concerning the use of botulinum neurotoxin (BoNT) in the
      treatment of writer's cramp (WC). Publications were categorized as Classes I-IV
      using the scale developed by the Therapeutics and Technology Assessment (TTA)
      subcommittee of the American Academy of Neurology. Our search resulted in 17
      clinical publications discussing the treatment of WC with BoNT. The literature
      search results were: one publication being Class I, two being Class II, 11 being
      Class III, and three being Class IV.

PMID- 18322640
TI  - Biochemical characterization of novel glucokinase mutations isolated from Spanish
      maturity-onset diabetes of the young (MODY2) patients.
AB  - Mature-onset diabetes of the young, type 2 (MODY2) is associated with mutations
      in the glucokinase (GCK) gene that result in impaired glucokinase activity.
      Although more than 200 inactivating GCK mutations have been reported, only less
      than 20% of these mutations have been functionally characterized. In this work,
      we describe the biochemical characterization of six missense glucokinase
      mutations associated with MODY2 from Spanish patients, namely, Y61S, V182L,
      C233R, E265K, A379V, and K420E. All these mutations produced enzymes that
      presented reduced enzymatic activity in various degrees, from a mild affectation
      (K420E) to a more severe effect (C233R). Mutation severity correlated with the
      importance of the structural changes introduced by the mutations. For example,
      C233R affected a critical residue of the active center of the enzyme and rendered
      a protein with undetectable enzymatic activity. These data add new information on
      the structure-function relationship of human glucokinase.

PMID- 18322639
TI  - The use of botulinum neurotoxin type A (BoNTA) in urology.
AB  - The use of Botulinum neurotoxin type A (BoNT/A) in the lower urinary tract was
      pioneered as early as 20 years ago with injections into the urethral sphincter
      reducing bladder voiding pressures, urethral pressures, and post-void residual
      urine. Over the past 9 years, the use of BoNT/A has revolutionised the treatment
      of intractable symptoms associated with the neurogenic or idiopathic overactive
      bladder, both in adults and children. The duration of clinical improvement is 6
      11 months, is accompanied by significant amelioration of patients' quality of
      life and repeat bladder treatments appear to have sustained effects. Despite
      evidence for an effect on the afferent pathways, its mode of action in the human
      bladder remains largely unknown. The use of BoNT/A has also expanded into the
      painful bladder syndrome and in benign prostatic diseases, with promising
      preliminary results. This review aims to provide an insight of the use of BoNT/A
      in the lower urinary tract, addressing issues such as treatment outcomes and
      safety, mechanisms of action and potential for future research.

PMID- 18322641
TI  - Identification and characterization of cryptic SHOX intragenic deletions in three
      Japanese patients with Leri-Weill dyschondrosteosis.
AB  - Although short-stature homeobox-containing gene (SHOX ) haploinsufficiency is
      responsible for Leri-Weill dyschondrosteosis (LWD), the molecular defect has not
      been identified in approximately 20% of Japanese LWD patients. Furthermore,
      although high prevalence of microdeletions affecting SHOX is primarily ascribed
      to the presence of repeat sequences such as Alu elements around SHOX, it remains
      to be determined whether microdeletions are actually mediated by repeat
      sequences. We performed multiple ligation probe amplification (MLPA) assay in six
      Japanese LWD patients with apparently normal SHOX, followed by fluorescent in
      situ hybridization (FISH) analysis and sequencing for polymerase chain reaction
      (PCR) products encompassing the deletion junctions in patients with abnormal MLPA
      patterns. Consequently, heterozygous intragenic deletions were identified in
      three cases, i.e., a 5,906-bp deletion involving exons 4-5 in case 1, a 5,594-bp
      deletion involving exons 4-6a in case 2, and a 50,199-bp deletion involving exons
      4-6b in case 3. The deletion breakpoints of cases 1 and 2 were present in
      nonrepeat sequences, whereas those of case 3 resided within Alu elements. The
      results suggest that cryptic SHOX intragenic deletions account for a small
      fraction of LWD and that microdeletions affecting SHOX can be generated by repeat
      sequence-mediated aberrant recombinations and by nonhomologous end joining.

PMID- 18322642
TI  - Introduction of a CD40L genomic fragment via a human artificial chromosome vector
      permits cell-type-specific gene expression and induces immunoglobulin secretion.
AB  - Gene therapy using cDNA driven by an exogenous promoter is not suited for genetic
      disorders that require intrinsic expression of a transgene, such as
      hyperimmunoglobulin (Ig)M syndrome (HIGM), which is caused by mutations in the
      CD40L gene. The human artificial chromosome (HAC) vector has the potential to
      solve this problem, because it can be used to transfer large genomic fragments
      containing their own regulatory elements. In this study, we examined whether
      introduction of a genomic fragment of CD40L via the HAC vector permits intrinsic
      expression of the transgene and has an effect on immunoglobulin secretion. We
      constructed an HAC vector carrying the mouse CD40L genomic fragment (mCD40L-HAC)
      in Chinese hamster ovary (CHO) cells and transferred the mCD40L-HAC vector into a
      human CD4-positive active T-cell line (Jurkat) and a human myeloid cell line
      (U937) via microcell-mediated chromosome transfer (MMCT). The mCD40L-HAC vector
      permits mCD40L expression in human active T cells but not in human myeloid cells.
      The mCD40L-HAC also functions to stimulate mouse B cells derived from CD40L(-/-)
      mice, inducing secretion of IgG. This study may be an initial step toward the
      therapeutic application of HAC vectors for intrinsic expression of genes, a
      potential new direction for genome-based gene therapy.

PMID- 18322643
TI  - Myeloperoxidase gene sequence variations are associated with low-density
      lipoprotein characteristics.
AB  - The small, dense low-density-lipoprotein (LDL) phenotype is associated with an
      increased atherosclerosis risk. A genome-wide scan performed on 236 nuclear
      families of the Quebec Family Study (QFS) revealed a quantitative trait locus
      (QTL) for LDL peak-particle size (LDL-PPD) on the 17q21 region. This region
      encodes the myeloperoxidase (MPO) gene. MPO is able to oxidize LDL by its
      reactive intermediates. To test the associations between MPO gene polymorphisms
      and LDL-PPD as well as plasma lipid levels, we performed direct sequencing of the
      coding regions, exon-intron splicing boundaries, and the regulatory regions on 25
      subjects to identify new genetic variants. Genotyping was performed either by
      TaqMan or direct sequencing on 680 subjects in the QFS. LDL-PPD was measured by
      gradient gel electrophoresis (GGE) on nondenaturing 2-16% polyacrylamide gradient
      gels. MPO gene sequencing revealed 16 polymorphisms. The c.-653G > A MPO
      polymorphism was associated with lower plasma total cholesterol, LDL cholesterol
      (LDL-C), and LDL apolipoprotein B (LDL-apoB) levels (P = 0.026, 0.042 and 0.014,
      respectively). No significant association with a gene-dosage effect were observed
      for LDL-PPD. The MPO gene variants are not associated with LDL-PPD and thus are
      unlikely to be responsible for the quantitative trait locus reported on 17q21.
      However, the c.-653G > A is associated with plasma LDL-C and LDL-apoB
      concentrations.

PMID- 18322644
TI  - Efficacy and safety of tacrolimus treatment for rheumatoid arthritis patients
      undergoing hemodialysis.
AB  - Rheumatoid arthritis (RA) is an autoimmune disorder characterized by progressive
      joint destruction that requires aggressive treatment using appropriate disease
      modifying antirheumatic drugs (DMARDs). RA patients with renal failure, however,
      are intolerant to most DMARDs due to the potential toxicity. In Japan, tacrolimus
      was approved for the treatment of RA in 2005. Based on its pharmacokinetics,
      tacrolimus may be administered to the patients undergoing hemodialysis. We report
      two cases of RA patients on hemodialysis treated effectively and safely with
      tacrolimus.

PMID- 18322645
TI  - Positive selection targeting the cathelin-like domain of the antimicrobial
      cathelicidin family.
AB  - The cathelin-like domain (CLD) of cathelicidins is grouped in the same
      superfamily with cystatins, natural cysteine protease inhibitors, due to their
      structural similarity. Intriguingly, human hCAP-18/LL37 and pig protegrin-3 (PG3)
      CLDs exhibit opposite effects against cathepsin L. Here, I evaluated the
      functional importance of the CLD through identifying whether positive selection
      has driven adaptive evolution of this domain. As a result, four positively
      selected sites were detected and three of them are located on a loop region
      previously recognized as a key determinant of the activating effect of the PG3
      CLD. Analysis of amino acid variability of the CLD led to the discovery of a
      conserved region and three highly variable regions, in which two are subjected to
      positive selection. Positive selection targeting the variable regions provides a
      starting point for experimentally establishing a direct link between the observed
      amino acid changes and functional divergence of the CLD family.

PMID- 18322646
TI  - Mitochondrial association of alpha-synuclein causes oxidative stress.
AB  - Alpha-synuclein is a neuron-specific protein that contributes to the pathology of
      Parkinson's disease via mitochondria-related mechanisms. The present study
      investigated possible interaction of alpha-synuclein with mitochondria and
      consequences of such interaction. Using SHSY cells overexpressing alpha-synuclein
      A53T mutant or wild-type, as well as isolated rat brain mitochondria, the present
      study shows that alpha-synuclein localizes at the mitochondrial membrane. In both
      SHSY cells and isolated mitochondria, interaction of alpha-synuclein with
      mitochondria causes release of cytochrome c, increase of mitochondrial calcium
      and nitric oxide, and oxidative modification of mitochondrial components. These
      findings suggest a pivotal role for mitochondria in oxidative stress and
      apoptosis induced by alpha-synuclein.

PMID- 18322647
TI  - Coilin levels and modifications influence artificial reporter splicing.
AB  - Cajal bodies (CBs) and Gems are nuclear domains that contain factors responsible
      for spliceosomal small nuclear ribonucleoprotein (snRNP) biogenesis. The marker
      protein for CBs is coilin. In addition to snRNPs, coilin and other factors,
      canonical CBs contain the survivor of motor neuron protein (SMN). SMN can also
      localize to Gems. Considering the important role that coilin plays in the
      formation and composition of CBs, we tested the splicing efficiency of several
      cell lines that vary in regards to coilin level and modification using an
      artificial reporter substrate. We found that cells with both hypomethylated
      coilin and Gems are more efficient at reporter splicing compared to cells in
      which SMN localizes to CBs. In contrast, coilin reduction, which induces Gem
      formation, decreases cell proliferation and artificial reporter splicing. These
      findings demonstrate that coilin modifications or levels impact artificial
      reporter splicing, possibly by influencing snRNP biogenesis.

PMID- 18322648
TI  - The ABBA family of aromatic prenyltransferases: broadening natural product
      diversity.

PMID- 18322649
TI  - Molecular mechanisms of phagocytic uptake in mammalian cells.
AB  - Phagocytosis is a highly conserved, complex process that has evolved to counter
      the constant threat posed by pathogens, effete cells and debris. Classically
      defined as a mechanism for internalising and destroying particles greater than
      0.5 mum in size, it is a receptor-mediated, actin-driven process. The best
      studied phagocytic receptors are the opsono-receptors, FcgammaR and CR3.
      Phagocytic uptake involves actin dynamics including polymerisation, bundling,
      contraction, severing and depolymerisation of actin filaments. Recent evidence
      points to the importance of membrane remodelling during phagocytosis, both in
      terms of changes in lipid composition and delivery of new membrane to the sites
      of particle binding. Here we review the molecular mechanisms of phagocytic uptake
      and some of the strategies developed by microbial pathogens to manipulate this
      process.

PMID- 18322650
TI  - Regulatory mechanisms of atrial fibrotic remodeling in atrial fibrillation.
AB  - Electrical, contractile and structural remodeling have been characterized in
      atrial fibrillation (AF), and the latter is considered to be the major
      contributor to AF persistence. Recent data show that interstitial fibrosis can
      predispose to atrial conduction impairment and AF induction. The interplay
      between cardiac matrix metalloproteinases (MMPs) and their endogenous inhibitors,
      tissue inhibitors of MMPs (TIMPs), is thought to be critical in atrial
      extracellular matrix (ECM) metabolism. At the molecular level, angiotensin II,
      transforming growth factor-beta1, inflammation and oxidative stress are
      particularly important for ECM dysregulation and atrial fibrotic remodeling in
      AF. Therefore, we review recent advances in the understanding of the atrial
      fibrotic process, the major downstream components in this remodeling process, and
      the expression and regulation of MMPs and TIMPs. We also describe the activation
      of bioactive molecules in both clinical studies and animal models to modulate
      MMPs and TIMPs and their effects on atrial fibrosis in AF.

PMID- 18322651
TI  - Methyl-CpG binding proteins: specialized transcriptional repressors or structural
      components of chromatin?
AB  - DNA methylation is an epigenetic modification that is implicated in
      transcriptional silencing. It is becoming increasingly clear that both correct
      levels and proper interpretation of DNA methylation are important for normal
      development and function of many organisms, including humans. In this review we
      focus on recent advances in understanding how proteins that bind to methylated
      DNA recognize their binding sites and translate the DNA methylation signal into
      functional states of chromatin. Although the function of methyl-CpG binding
      proteins in transcriptional repression has been attributed to their cooperation
      with co-repressor complexes, additional roles for these proteins in chromatin
      compaction and spatial organization of nuclear domains have also been proposed.
      Finally, we provide a brief overview of how methyl-CpG proteins contribute to
      human disease processes such as Rett syndrome and cancer.

PMID- 18322652
TI  - Modulation of key signal transduction molecules by a novel peptide combination
      effective for the treatment of gastrointestinal carcinomas.
AB  - We have reported earlier a novel combination of four structurally designed
      synthetic neuropeptide analogs of vasoactive intestinal peptide (VIP), bombesin,
      substance P and somatostatin, code-named DRF 7295 which have anti-tumor efficacy
      for adenocarcinomas in vitro and in vivo (Jaggi et al., Invest New Drugs, 2008).
      The discovery, synthesis, in vitro and in vivo efficacy was reported (Jaggi et
      al., Invest New Drugs, 2008). Gastrointestinal tumor cells of the colon, pancreas
      and duodenum were found to most sensitive to DRF7295 in vitro and in vivo (Jaggi
      et al., Invest New Drugs, 2008). We have further investigated and report here the
      modulation of cellular signaling in gastrointestinal carcinomas by DRF 7295,
      which may be mediating its observed anticancer activity in these cancer types.
      DRF 7295 inhibits the binding of specific neuropeptides initiating a cascade of
      cellular signaling events leading to programmed cell death. It down regulates the
      second messenger cAMP, epidermal growth factor (EGF) dependent proliferation and
      the phosphorylated MAP Kinase pERK1/2 in gastrointestinal carcinomas, thus
      depriving the tumour cells of critical pro-proliferative cellular signals. It
      triggers bcl2 and Caspase 3 dependent apoptotic cell death and induces p53 tumor
      suppressor protein in the treated carcinoma cells in vitro. It has significant
      anti-angiogenic potential as reflected in the inhibition of tube like formation
      in the endothelial cells and down regulation of VEGF levels. Tumour xenograft
      studies confirmed the in vivo efficacy of DRF 7295 for gastrointestinal
      carcinomas (Jaggi et al., Invest New Drugs, 2008). The Phase I clinical trials
      have shown DRF 7295 to be well tolerated and devoid of systemic toxicities of the
      conventional cytotoxics (Mukherjee et al., Phase I dose escalating study of
      DRF7295: a new class of peptide based drugs. "Abstract" ASCO ID:948, 2003). The
      drug may have a promising role in disease stabilization in colorectal and other
      cancers. Thus DRF 7295 is a novel targeted drug in the class of signal
      transduction modulators, with potential for treatment of gastrointestinal
      carcinomas.

PMID- 18322653
TI  - Investigation of ascorbate-mediated iron release from ferric phytosiderophores in
      the presence of nicotianamine.
AB  - Phytosiderophores (PS) are strong iron chelators, produced by graminaceous plants
      under iron deficiency. The ability of released PS to chelate iron(III), and
      subsequent uptake of this chelate into roots by YS1-type transport proteins, are
      well-known. The mechanism of iron release from the stable chelate inside the
      plant cell, however, is unclear. One possibility involves the reduction of ferric
      PS in the presence of an iron(II) chelator via ternary complex formation. Here,
      the conversion of ferric PS species by ascorbate in the presence of the
      intracellular ligand nicotianamine (NA) has been investigated at cytosolic pH (pH
      7.3), leading to the formation of a ferrous NA chelate. This reaction takes place
      when supplying Fe(III) as a chelate with 2'-deoxymugineic acid (DMA), mugineic
      acid (MA), and 3-epi-hydroxymugineic acid (epi-HMA), with the reaction rate
      decreasing in this order. The progress of the conversion of ferric DMA to ferrous
      NA was monitored in real-time by high resolution mass spectrometry (FTICR-MS),
      and the results are complemented by electrochemical measurements (cyclic
      voltammetry), which allows detecting reactive intermediates and their change with
      time at high sensitivity. Hence, the combined results of electrochemistry and
      mass spectrometry indicate an ascorbate-mediated mechanism for the iron release
      from ferric PS, which highlights the role of ascorbate as a simple, but effective
      plant reductant.

PMID- 18322654
TI  - The tumor supressor function of STGC3 and its reduced expression in
      nasopharyngeal carcinoma.
AB  - STGC3 is a novel candidate tumor suppressor gene that was found to be associated
      with nasopharyngeal carcinoma (NPC) via the cDNA cloning and RACE processes. The
      biological function of the STGC3 protein and its expression level in
      nasopharyngeal carcinoma remain unknown. This study aimed to evaluate the STGC3
      protein expression level in NPC and to investigate the inhibitory function of
      STGC3 as a candidate tumor suppressor gene. We assessed the expression of the
      STGC3 protein in NPC biopsies and normal control specimens via Western blot and
      immunohistochemical analysis. The expression of STGC3 as induced by doxycycline
      (Dox) via a tetracycline (Tet)-regulated system in human nasopharyngeal carcinoma
      cell line CNE2 was also established, and the effect of STGC3 restoration on the
      biological behavior of CNE2 was observed. A reduced level of STGC3 expression
      (0.978 +/- 0.213 versus 0.324 +/- 0.185, P < 0.05) was detected in NPC versus
      normal nasopharyngeal tissue by Western blot assay. Immunohistochemical assays
      for STGC3 detected positive staining in the nuclei and cytoplasm of epithelial
      cells, and the positive expression rate in NPC, 8 of 21 (38%), was lower than
      that in normal nasopharynx samples, 16 of 22 (72%). After STGC3 expression was
      restored, the growth capacity and clone formation potential of CNE2 cells in soft
      agar were significantly suppressed, and the cell percentage in G(0)/G(1) phase
      increased, while the percentage of cells entering the S and G(2) phases
      decreased. This indicates that an abnormality in STGC3 expression is associated
      with nasopharyngeal carcinogenesis and that it may play an important role in
      controlling cell growth and regulating the cell cycle.

PMID- 18322655
TI  - Trace element levels in hashimoto thyroiditis patients with subclinical
      hypothyroidism.
AB  - The present study was conducted to evaluate the serum copper, zinc, magnesium,
      and selenium levels in patients with subclinical hypothyroidism in the iodine
      rich region of Ankara, Turkey. The effects of hormone replacement therapy on
      these elements were also studied in these patients. Basal levels of selenium and
      iron in patients were significantly lower than control group (67.7 +/- 10.4 vs.
      83.7 +/- 17.3 microg/dl, p = 0.02; 55.7 +/- 38 vs 275.7 +/- 24, P = 0.03
      microg/dl). Serum magnesium levels were significantly higher in patient group
      (2.16 +/- 0.31 vs 1.95 +/- 0.13 mg/dl, P < 0.0001). There was a correlation
      between selenium levels with hsCRP (r = -0.408, p = 0.007). HsCRP levels in
      patients with selenium levels <80 microg/l (n = 31) was significantly higher than
      hsCRP levels in patients with selenium levels >80 microg/l (n = 12; 1.99 +/- 1.0;
      1.02 +/- 0.9, p = 0.014). None of these biochemical risk factors and trace
      elements have changed after euthyroidism in patients with SH when compared to
      pretreatment levels. Selenium deficiency may contribute to cardiovascular disease
      risk in these patients.

PMID- 18322656
TI  - Risk assessment of metals from consuming vegetables, fruits and rice grown on
      soils irrigated with waters of the Ebro River in Catalonia, Spain.
AB  - The concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu),
      mercury (Hg), manganese (Mn), nickel (Ni), and lead (Pb) were determined in
      samples of various edible vegetables (artichoke, cauliflower, lettuce, tomato),
      fruits (apple, mandarin, orange, pear) and rice grown in soils irrigated with
      water from the Ebro River in Tarragona Province (Catalonia, Spain). Although all
      food items were randomly acquired in various localities of the area, the local
      origin was always verified. Arsenic was only detected in rice (all samples) and
      apple (one sample), while Cd and Hg could not be detected in any of the samples.
      In general terms, metal concentrations were quite similar or lower than the
      levels recently reported in the literature. The health risks caused by metal
      exposure from consuming these agricultural products were assessed for the Catalan
      population living in the zone under evaluation. For all elements, when the lower
      bound values were considered, the Hazard Quotient (HQ) was <1, while using the
      Upper bound values, only for As (children and male seniors) HQ was >1. The intake
      of the analyzed elements through consumption of the nine selected food items does
      not mean additional health risks for the consumers of the area.

PMID- 18322657
TI  - A giant cystic pheochromocytoma of the adrenal gland.
AB  - Adrenal pheochromocytomas are rare catecholamine-secreting tumors that originate
      from chromaffin cells in the adrenal medulla, and giant pheochromocytomas with
      cystic changes are particularly rare. We report a case of a 46-year-old man who
      presented with episodic hypertension and headache. Radiographic studies showed an
      18-cm cystic mass in the left upper quadrant of the abdomen; further workups,
      which included light microscopy, immunohistochemical, and electron microscopic
      analysis, revealed a pheochromocytoma of the left adrenal gland. Cytogenetic
      analysis and genetic mutation analyses for von-Hippel-Lindau (VHL), rearranged
      during transfection (RET), and succinate dehydrogenase complex subunit B (SDHB)
      genes were also performed but failed to reveal any abnormalities within the tumor
      cells.

PMID- 18322658
TI  - Chondroprotective effect of salicylate and chloroquine in pyogenic septic
      arthritis.
AB  - INTRODUCTION: This study aims to investigate the effectiveness of salicylate
      (Aspisol; Bayer AG, Leverkusen, Germany) and chloroquine on preventing cartilage
      damage in septic arthritis. METHODS: A septic arthritis model was created by
      inoculating the knee joint of young rabbits (n=21) with Staphylococcus aureus.
      Some rabbits with inflicted septic arthritis did not undergo any treatment and
      served as the control group (n=7). The second group (n=7) was started on
      salicylate on day 2 to investigate the effects of salicylate on joint cartilage.
      The third group (n=7) was started on chloroquine on day 2 to investigate the
      effects of chloroquine on joint cartilage. All three groups underwent arthrotomy,
      drainage and synoviectomy on day 7 of the experiment. Animals were sacrificed on
      day 14 and the joint cartilages were extracted. Histopathology, determination of
      local prostaglandin (PGE)-like activity, and evaluation of hyaluronic acid loss
      were performed on all samples. RESULTS: The control group and the salicylate
      group were similar in the extent of joint damage. Salicylate did not prevent
      joint cartilage damage despite inhibiting PGE synthesis. Chloroquine, despite not
      inhibiting PGE synthesis, did prevent cartilage destruction. CONCLUSION: If
      supported by larger-scale studies, chloroquine could be added to the antibiotic
      regimen in the treatment of septic arthritis to prevent cartilage damage.

PMID- 18322659
TI  - Fibrin glue and transanal rectal advancement flap for high transsphincteric
      perianal fistulas; is there any advantage?
AB  - BACKGROUNDS AND AIM: In recent decades, fibrin glue has appeared as an
      alternative treatment for high perianal fistulas. Early results seemed promising,
      with high success rates being reported. However, with increasing follow-up, the
      enthusiasm was tempered because of disappointing results. The aim of this
      retrospective study was to assess the additional value of fibrin glue in
      combination with transanal advancement flap, compared to advancement flap alone,
      for the treatment of high transsphincteric fistulas of cryptoglandular origin.
      MATERIALS AND METHODS: Between January 1995 and January 2006, 127 patients were
      operated for high perianal fistulas with an advancement flap. After exclusion of
      patients with inflammatory bowel disease or HIV, 80 patients remained. A
      consecutive series of 26 patients had an advancement flap combined with
      obliteration of the fistula tract with fibrin glue. Patients were matched for
      prior fistula surgery, and the advancement was performed identically in all
      patients. In the fibrin glue group, glue was installed retrogradely in the
      fistula tract after the advancement was completed and the fistula tract had been
      curetted. RESULTS: Minimal follow-up after surgery was 13 months [median of 67
      months (range, 13-127)]. The overall recurrence rate was 26% (n=21). Recurrence
      rates for advancement flap alone vs the combination with glue were 13% vs 56%
      (p=0.014) in the group without previous fistula surgery and 23% vs 41% (p=0.216)
      in the group with previous fistula surgery. CONCLUSION: Obliterating the fistula
      tract with fibrin glue was associated with worse outcome after rectal advancement
      flap for high perianal fistulas.

PMID- 18322660
TI  - hTERT expression in colorectal adenocarcinoma: correlations with p21, p53
      expressions and clinicopathological features.
AB  - BACKGROUND: The clinicopathological roles and relationships of hTERT, p21 and p53
      proteins have not been studied in depth in colorectal cancer. The aim of the
      present study is to investigate the clinicopathological roles of expression of
      hTERT protein expression and its relationship with the expression of p21 and p53
      proteins in a large cohort of patients with colorectal adenocarcinoma. MATERIALS
      AND METHODS: Expressions of hTERT, p21 and p53 proteins were investigated in 188
      patients with colorectal adenocarcinomas by immunohistochemistry. The findings
      were correlated with the clinicopathological features and survival data of
      colorectal adenocarcinomas. RESULTS: hTERT, p53 and p21 proteins were detected in
      63%, 100% and 62% of the patients with colorectal carcinoma. High level of hTERT
      protein expression was noted in patients with metastases (p = 0.038) and in
      patients with rectal cancer (p = 0.046). Loss or low level of p21 protein was
      often noted in non-mucinous colorectal adenocarcinoma when compared with mucinous
      adenocarcinoma (p = 0.001). Furthermore, p53 expression was more frequently noted
      in non-mucinous adenocarcinoma (p = 0.001). The level of expression of p21
      protein was positively correlated with expression of level of hTERT protein (p =
      0.00001). The survival of the patients was related to staging (p = 0.001) and p53
      protein expression (p = 0.038) of the tumours. CONCLUSIONS: hTERT protein
      expression is an indicator of the biological aggressiveness of the cancer. The
      level of expression of the protein was also related to the distal location and
      level of p21 expression of the tumours.

PMID- 18322661
TI  - Colorectal carcinoma prognosis can be predicted by alterations in gene p53 exons
      5 and 8.
AB  - BACKGROUND AND AIMS: Gene p53 alteration is a genetic event described in the
      progression from adenoma to colorectal carcinoma. Most of the p53 mutations occur
      in exons 5 to 8 in highly preserved regions and in the three main structural
      domains of the p53 protein. It is possible that mutations affecting different
      structural regions may present different effects on the p53 protein function and,
      due to this, they may have different prognostic meaning. MATERIALS AND METHODS:
      The study population consisted of 353 patients diagnosed with sporadic colorectal
      cancer. Mutations in 5-8 exons of p53 gene were detected by means of single
      strand conformation polymorphism (SSCP). All samples that showed different
      migration bands in SSCP were confirmed by sequencing. RESULTS: A total of 69
      patients (19.7%) showed alterations of the gene p53. It was observed that
      mutation in codon 175 in exon 5 was related to tumors located in the colon (p =
      0.01) and the mutation in the codon 288 in exon 8 was related to rectal tumors (p
      = 0.02). In the study of overall survival, mutation in codon 175 of exon 5
      conferred a better prognosis and alterations of exon 8 were related to a worse
      prognosis in different population subgroups: in men, in patients younger than 71
      years old, in the tumors located in the proximal colon, the ones moderately
      differentiated, and those that are mucinous. CONCLUSION: According to this study,
      mutations in different exons of p53 are related to different phenotypes in
      colorectal cancer. These phenotypes could mean differences in the clinical
      evolution of the patients.

PMID- 18322662
TI  - Case report: Congenital knee dislocation in a patient with larsen syndrome and a
      novel filamin B mutation.
AB  - We treated a patient with multiple congenital joint dislocations and facial
      dysmorphisms consistent with Larsen syndrome. Sequencing of the FLNB gene
      resulted in identification of a novel, de novo 508G>C point mutation resulting in
      substitution of proline for a highly conserved alanine (A170P). This mutation has
      not been described previously but is likely causative because this alanine is
      highly conserved and is located in the calponin homology domain where other
      mutations have been described. We also report the successful use of a minimally
      invasive technique in achieving initial correction of bilateral congenital knee
      dislocations in this patient. The technique consists of serial manipulations and
      castings followed by an open quadriceps tenotomy. Longer followup is needed to
      ensure maintenance of correction and to avoid the need for more extensive
      surgery, which has been the traditional treatment for congenital knee dislocation
      associated with Larsen syndrome.

PMID- 18322663
TI  - Consequences of scapular anatomy for reversed total shoulder arthroplasty.
AB  - The reverse total shoulder prosthesis provides successful functional outcome in
      many patients with rotator cuff tear arthropathy. However, scapular notching, a
      direct consequence of mechanical impingement between the humeral prosthesis and
      the glenoid, remains a major concern. We presumed a better knowledge of the
      anatomy of the scapula would enable design or placement modifications to minimize
      this phenomenon. After establishing a uniform spatial reference system using easy
      locatable surgical reference points and planes, we analyzed 200 dry bony scapulae
      and defined the glenoid and infraglenoid anatomy relative to the reference
      system. The bony rim of the two inferior quadrants of the glenoid forms a
      semicircle the center of which can be used perioperatively as an easy locatable
      bony reference point. The infraglenoid tubercle varies in width and length, and
      can interfere with the humeral part of the reverse prosthesis, creating scapular
      notching. To avoid notching, we suggest using a convex base plate with a smaller
      radius than currently used, placing it as low as possible with a 42-mm
      glenosphere eccentrically assembled to create a posterior offset. If prosthetic
      overhang cannot be obtained, we suggest removing part of the infraglenoid
      tubercle.

PMID- 18322664
TI  - [Advanced life support under special circumstances: part 1].
AB  - Based on the 2005 International Consensus Conference on Cardiopulmonary
      Resuscitation and Emergency Cardiovascular Care Science with Treatment
      Recommendations of the International Liaison Committee on Resuscitation (ILCOR),
      guidelines were published for managing basic and advanced life-saving procedures
      in the event of cardiac arrest. The fact that special circumstances sometimes
      must be considered in patient treatment resulted in a separate chapter. This
      first part of a two-part article reviews essential information as well as
      necessary modifications of the standard advanced life support algorithm in cases
      of life-threatening drowning, asthma, anaphylaxis, and poisoning. The second part
      will deal with electrolyte disorders, hypothermia, electrical emergencies,
      trauma, cardiac arrest during pregnancy, and cardiac surgery.

PMID- 18322665
TI  - [Target-controlled infusion (TCI) - a concept with a future?: state-of-the-art,
      treatment recommendations and a look into the future].
AB  - Over the last 10 years the technique of target-controlled infusion (TCI) has
      substantially influenced the development and practice of intravenous anaesthesia.
      It opened the possibility of many new and exciting applications of perioperative
      anaesthetic care. More recent and current developments, such as open TCI (target
      controlled infusion) and the availability of generic anaesthetic agents combined
      with modern infusion pumps, means that TCI can become a standard procedure in
      anaesthesia and is no longer just a research tool for specialists and
      enthusiasts. This review explains the fundamentals and applications of
      intravenous drug delivery by TCI and gives practice guidelines to successfully
      implement the technique into clinical practice. The aim is to provide a
      comprehensive reference based on clinically proven evidence.

PMID- 18322666
TI  - [Obesity and heart failure].
AB  - Obesity doubles the risk of heart failure independent of comorbidities like
      hypertension or coronary artery disease potentially mediated by altered
      hemodynamics to compensate increased mass and metabolic activity. Symptoms of
      obesity cardiomyopathy do not differ from other forms of cardiomyopathy, but may
      be easily mixed up with obesity associated symptoms. The diagnosis can be made
      with imaging techniques like echocardiography or magnetic resonance imaging.
      Therapeutic approaches include weight control by dietary intervention and
      exercise, as well as bariatric surgery for the morbidly obese. Heart failure
      treatment should otherwise follow the general heart failure guidelines.

PMID- 18322667
TI  - [A 52-year-old woman with acute shock and purpura fulminans. Pneumococcal
      sepsis].
AB  - We report a 52-year-old female patient admitted with fever, chills, and myalgias
      since the previous day. On the day of admission she had a generalized seizure.
      The patient had no previous illnesses. Laboratory investigations showed
      consumptive coagulopathy with clinical manifestations of shock and development of
      multiple organ failure. Pneumococci were detected in blood cultures. Furthermore
      the skin showed purpura fulminans all over. The patient died within 24 h after
      admission in the intensive care unit. On autopsy, in addition to adrenal and
      myocardial hemorrhages, hypoplasia of the spleen was found. Fulminant
      pneumococcal sepsis is a life-threatening disease that occurs in patients with
      risk factors like splenic hypoplasia or asplenia. Sometimes a fulminant
      pneumococcal sepsis may be the first clinical manifestation of a hitherto unknown
      splenic hypoplasia. In this context the general recommendation of vaccination
      against pneumococci in patients with risk factors like splenic hypoplasia or
      asplenia, in patients older than 60, and in children from 2 months onward has to
      be emphasized.

PMID- 18322668
TI  - The (pro)renin receptors.
AB  - Two (pro)renin receptors have been characterized so far, the mannose-6-phosphate
      receptor (M6P-R) and a specific receptor called (P)RR for (pro)renin receptor.
      Each receptor controls a different aspect of renin and prorenin metabolism. The
      M6P-R is a clearance receptor, whereas (P)RR mediates their cellular effects by
      activating intracellular signaling and up-regulating gene expression. Moreover,
      binding to (P)RR increases renin enzymatic activity and fully activates prorenin,
      the inactive proenzyme form of renin. Experimental models suggest that increased
      (P)RR synthesis and/or activation may be relevant to diseases, especially to high
      blood pressure, to cardiac fibrosis associated with hypertension, and to diabetic
      nephropathy.

PMID- 18322669
TI  - Prorenin anno 2008.
AB  - For many years, prorenin has been considered to be nothing more than the inactive
      precursor of renin. Yet, its elevated levels in diabetic subjects with
      microvascular complications and its extrarenal production at various sites in the
      body suggest otherwise. This review discusses the origin, regulation, and
      enzymatic activity of prorenin, its role during renin inhibition, and the
      angiotensin-dependent and angiotensin-independent consequences of its binding to
      the recently discovered (pro)renin receptor. The review ends with the concept
      that prorenin rather than renin determines tissue angiotensin generation.

PMID- 18322670
TI  - S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and
      regeneration in diseases?
AB  - Multiple reports have focused on S100A4's role in cancer progression,
      specifically its ability to enhance metastasis. However, recent studies have
      linked S100A4 to several diseases besides cancer, including kidney fibrosis,
      cirrhosis, pulmonary disease, cardiac hypertrophy and fibrosis, arthritis and
      neuronal injuries. Common to all these diseases is the involvement of fibrotic
      and inflammatory processes, i.e. processes greatly dependent on tissue
      remodelling, cell motility and epithelial-mesenchymal transition. Therefore, the
      basic biological mechanisms behind S100A4's effects are emerging. S100A4 belongs
      to the S100 family of proteins that contain two Ca2+-binding sites including a
      canonical EF-hand motif. S100A4 is involved in the regulation of a wide range of
      biological effects including cell motility, survival, differentiation and
      contractility. S100A4 has both intracellular and extracellular effects. Hence,
      S100A4 interacts with cytoskeletal proteins and enhances metastasis of several
      types of cancer cells. In addition, S100A4 is secreted by unknown mechanisms,
      thus, paracrinely stimulating a variety of cellular responses, including
      angiogenesis and neuronal growth. Although many cellular effects of S100A4 are
      well described, the molecular mechanisms whereby S100A4 elicits these responses
      remain largely unknown. However, it is likely that the intracellular and the
      extracellular effects involve distinct mechanisms. In this review, we explore the
      possible roles of S100A4 in non-cancer diseases and employ this knowledge to
      describe underlying biological mechanisms including a change in cellular
      phenotype towards less tightly adherent cells and activation of fibrotic
      processes that may explain this protein's involvement in multiple pathologies.

PMID- 18322671
TI  - Association of gene-linked SSR markers to seed glucosinolate content in oilseed
      rape (Brassica napus ssp. napus).
AB  - Breeding of oilseed rape (Brassica napus ssp. napus) has evoked a strong
      bottleneck selection towards double-low (00) seed quality with zero erucic acid
      and low seed glucosinolate content. The resulting reduction of genetic
      variability in elite 00-quality oilseed rape is particularly relevant with regard
      to the development of genetically diverse heterotic pools for hybrid breeding. In
      contrast, B. napus genotypes containing high levels of erucic acid and seed
      glucosinolates (++ quality) represent a comparatively genetically divergent
      source of germplasm. Seed glucosinolate content is a complex quantitative trait,
      however, meaning that the introgression of novel germplasm from this gene pool
      requires recurrent backcrossing to avoid linkage drag for high glucosinolate
      content. Molecular markers for key low-glucosinolate alleles could potentially
      improve the selection process. The aim of this study was to identify potentially
      gene-linked markers for important seed glucosinolate loci via structure-based
      allele-trait association studies in genetically diverse B. napus genotypes. The
      analyses included a set of new simple-sequence repeat (SSR) markers whose
      orthologs in Arabidopsis thaliana are physically closely linked to promising
      candidate genes for glucosinolate biosynthesis. We found evidence that four genes
      involved in the biosynthesis of indole, aliphatic and aromatic glucosinolates
      might be associated with known quantitative trait loci for total seed
      glucosinolate content in B. napus. Markers linked to homoeologous loci of these
      genes in the paleopolyploid B. napus genome were found to be associated with a
      significant effect on the seed glucosinolate content. This example shows the
      potential of Arabidopsis-Brassica comparative genome analysis for synteny-based
      identification of gene-linked SSR markers that can potentially be used in marker
      assisted selection for an important trait in oilseed rape.

PMID- 18322672
TI  - Comparison of two arthroscopic pump systems based on image quality.
AB  - The effectiveness of arthroscopic pump systems has been investigated with either
      subjective measures or measures that were unrelated to the image quality. The
      goal of this study is to determine the performance of an automated pump in
      comparison to a gravity pump based on objective assessment of the quality of the
      arthroscopic view. Ten arthroscopic operations performed with a gravity pump and
      ten performed with an automated pump (FMS Duo system) were matched on duration of
      the surgery and shaver usage, type of operation, and surgical experience. Quality
      of the view was defined by means of the presence or absence of previously
      described definitions of disturbances (bleeding, turbidity, air bubbles, and
      loose fibrous tissue). The percentage of disturbances for all operations was
      assessed with a time-disturbance analysis of the recorded operations. The Mann
      Whitney U test shows a significant difference in favor of the automated pump for
      the presence of turbidity only (Exact Sig. [2*(1-tailed Sig.)] = 0.015).
      Otherwise, no differences were determined (Exact Sig. [2*(1-tailed Sig.)] >
      0.436). A new objective method is successfully applied to assess efficiency of
      pump systems based on the quality of the arthroscopic view. Important
      disturbances (bleeding, air bubbles, and loose fibrous tissue) are not reduced by
      an automated pump used in combination with a tourniquet. The most frequent
      disturbance turbidity is reduced by around 50%. It is questionable if this result
      justifies the use of an automated pump for straightforward arthroscopic knee
      surgeries using a tourniquet.

PMID- 18322673
TI  - Arthroscopic reconstruction of a ruptured patellar tendon: a technical note.
AB  - A traumatic patellar tendon rupture of a 35-year-old, otherwise healthy male was
      reconstructed with semi-tendinosus and gracillis tendons. Tendon grafts were
      harvested with an open-ended tendon stripper without dissecting them free from
      their tibial insertion. A transpatellar tunnel was drilled appropriate to the
      tendon size and a passing pin was used across the length of the patella. Graft
      bundles were passed in a standard fashion, traversing through the midst of the
      distal part of the patellar tendon via a beath pin with a loaded looped suture.
      The endo-button device was then flipped and fixed as an anchor. The patella was
      positioned at the original placement under arthroscopic visualization and the
      free ends of the hamstring tendons were attached to a post-fixation screw through
      the Krackow sutures. Tendon grafts were gathered on the tuberositas tibia and
      fixed with two additional staples. The patient could flex his knee up to 130 deg
      at the 3-month follow-up. It was demonstrated that arthroscopic reconstruction of
      a ruptured patellar tendon may be the optimal surgical choice to minimize trauma
      and begin early rehabilitation.

PMID- 18322674
TI  - Health effects due to endotoxin inhalation (review).
AB  - Endotoxins are ubiquitous in the environment and represent important components
      of bioaerosols. High exposure occurs in rural environment and at several
      workplaces (e.g. waste collecting, textile industry etc.). Adverse effects on
      human health induced by inhalation of endotoxin are described in several studies.
      Up to now the endotoxin levels are mainly measured using the Limulus amoebocyte
      lysate (LAL) assay. This assay is well established, but for a suitable
      characterization of bioaerosols more parameters are necessary. Additional
      information, e.g. concerning the pyrogenic activity of organic dust samples may
      be delivered by whole blood assay. Whereas on the one hand protection measures at
      workplaces are demanded to avoid lung function impairment due to endotoxin
      exposure, on the other hand a protective effect of exposure to microbial agents
      like endotoxins with regard to allergy development has been observed. On the
      cellular level toll-like receptor 4 (TLR4) and IL-1 receptor as well as surface
      molecules like CD14 have been shown to play a pivotal role in the endotoxin
      activation cascade. In this review we summarize the mechanism of endotoxin
      recognition and its manifold effects on human health.

PMID- 18322675
TI  - Alternative methods to safety studies in experimental animals: role in the risk
      assessment of chemicals under the new European Chemicals Legislation (REACH).
AB  - During the last two decades, substantial efforts have been made towards the
      development and international acceptance of alternative methods to safety studies
      using laboratory animals. In the EU, challenging timelines for phasing out of
      many standard tests using laboratory animals were established in the seventh
      Amending Directive 2003/15/EC to Cosmetics Directive 76/768/EEC. In continuation
      of this policy, the new European Chemicals Legislation (REACH) favours
      alternative methods to conventional in vivo testing, if validated and
      appropriate. Even alternative methods in the status of prevalidation or
      validation, but without scientific or regulatory acceptance may be used under
      certain conditions. Considerable progress in the establishment of alternative
      methods has been made in some fields, in particular with respect to methods
      predicting local toxic effects and genotoxicity. In more complex important fields
      of safety and risk assessment such as systemic single and repeated dose toxicity,
      toxicokinetics, sensitisation, reproductive toxicity and carcinogenicity, it is
      expected that the development and validation of in silico methods, testing
      batteries (in vitro and in silico) and tiered testing systems will have to
      overcome many scientific and regulatory obstacles which makes it extremely
      difficult to predict the outcome and the time needed. The main reasons are the
      complexity and limited knowledge of the biological processes involved on one hand
      and the long time frame until validation and regulatory acceptance of an
      alternative method on the other. New approaches in safety testing and evaluation
      using "Integrated Testing Strategies" (ITS) (including combinations of existing
      data, the use of chemical categories/grouping, in vitro tests and QSAR) that have
      not been validated or not gained wide acceptance in the scientific community and
      by regulatory authorities will need a thorough justification of their
      appropriateness for a given purpose. This requires the availability of knowledge
      and experience of experts in toxicology. The challenging deadlines for phasing
      out of in vivo tests in the Cosmetics Amending Directive 2003/15/EC appear
      unrealistic. Likewise, we expect that the application of validated alternative
      methods will only have a small or moderate impact on the reduction of in vivo
      tests under the regimen of REACH, provided that at least the same level of
      protection of human health as in the past is envisaged. As a consequence, under
      safety aspects, it appears wise to consider established in vivo tests to be
      indispensable as basic tools for hazard and risk assessment with respect to
      systemic single and repeated dose toxicity, sensitisation, carcinogenicity and
      reproductive toxicity, especially regarding quantitative aspects of risk
      assessment such as NOAELs, LOAELs and health-related limit values derived from
      them. Based on the overall evaluation in this review, the authors are of the
      opinion that in the short- and mid-term, the strategy of the development of
      alternative methods should be more directed towards the refinement or reduction
      of in vivo tests. The lessons learnt during these efforts will provide a
      substantial contribution towards the replacement initiatives in the long-term.

PMID- 18322677
TI  - Individual differences in schedule-induced polydipsia and the role of gabaergic
      and dopaminergic systems.
AB  - RATIONALE: The research of individual differences has opened new possibilities
      for better exploring the neurobiological basis of vulnerability to
      psychopathological disorders. OBJECTIVE: We extended this approach by using
      schedule-induced polydipsia (SIP). METHODS: Outbred male Wistar rats were
      characterized as either high (HD) or low (LD) drinker according to their behavior
      in SIP. Subsequently, their performance in the elevated plus maze (EPM) was
      studied for possible differences in anxiety-like behaviors. Finally, the effects
      of pentylenetetrazol (PTZ), diazepam, d-amphetamine, and cocaine on individual
      differences in SIP were investigated. RESULTS: HD rats acquired SIP faster and
      reached higher asymptotic levels than LD. Nose pokes, however, were greater in
      LD. In the EPM, there were no differences between HD and LD animals. Gabaergic
      drug effects on SIP did not differ between HD and LD rats. Compared to saline,
      PTZ reduced and diazepam increased water SIP drinking. On the other hand,
      amphetamine dose-dependently reduced SIP in HD, whereas the highest dose was
      required to reduce SIP in LD. HD rats also showed reductions in SIP drinking
      after cocaine administration. However, the effects of these drugs on nose pokes
      did not differ between HD and LD. CONCLUSION: These data provide novel evidence
      that individual differences in SIP are not predictive of behavioral reactivity in
      animal models of anxiety and suggest an important role for the dopaminergic
      system in such individual differences. These findings point to SIP as a useful
      animal model for investigating the neurobiological basis of vulnerability to
      several psychopathologies in which the dopaminergic system is involved.

PMID- 18322676
TI  - Metabotropic glutamate receptor modulation, translational methods, and
      biomarkers: relationships with anxiety.
AB  - RATIONALE: The increasing awareness of the need to align clinical and preclinical
      research to facilitate rapid development of new drug therapies is reflected in
      the recent introduction of the term "translational medicine". This review
      examines the implications of translational medicine for psychiatric disorders,
      focusing on metabotropic glutamate (mGlu) receptor biology in anxiety disorders
      and on anxiety-related biomarkers. OBJECTIVES: This review aims to (1) examine
      recent progress in translational medicine, emphasizing the role that
      translational research has played in understanding of the potential of mGlu
      receptor agonists and antagonists as anxiolytics, (2) identify lacunas where
      animal and human research have yet to be connected, and (3) suggest areas where
      translational research can be further developed. RESULTS: Current data show that
      animal and human mGlu(5) binding can be directly compared in experiments using
      the PET ligand (11)C-ABP688. Testing of the mGlu(2/3) receptor agonist LY354740
      in the fear-potentiated startle paradigm allows direct functional comparisons
      between animals and humans. LY354740 has been tested in panic models, but in
      different models in rats and humans, hindering efforts at translation. Other
      potentially translatable methods, such as stress-induced hyperthermia and HPA
      axis measures, either have been underexploited or are associated with technical
      difficulties. New techniques such as quantitative trait loci (QTL) analysis may
      be useful for generating novel biomarkers of anxiety. CONCLUSIONS: Translational
      medicine approaches can be valuable to the development of anxiolytics, but the
      amount of cross-fertilization between clinical and pre-clinical departments will
      need to be expanded to realize the full potential of these approaches.

PMID- 18322678
TI  - Organosilica composite for preconcentration of phenolic compounds from aqueous
      solutions.
AB  - A new adsorbent is proposed for the solid-phase extraction of phenol and 1
      naphthol from polluted water. The adsorbent (TX-SiO(2)) is an organosilica
      composite made from a bifunctional immobilized layer comprising a major fraction
      (91%) of hydrophilic diol groups and minor fraction (9%) of the amphiphilic long
      chain nonionic surfactant Triton X-100 (polyoxyethylated isooctylphenol) (TX).
      Under static conditions phenol was quantitatively extracted onto TX-SiO(2) in the
      form of a 4-nitrophenylazophenolate ion associate with cetyltrimethylammonium
      bromide. The capacity of TX-SiO(2) for phenol is 2.4 mg g(-1) with distribution
      coefficients up to 3.4 x 10(4) mL g(-1); corresponding data for 1-naphthol are
      1.5 mg g(-1) and 3 x 10(3) mL g(-1). The distribution coefficient does not change
      significantly for solution volumes of 0.025-0.5 L and adsorbent mass less than
      0.03 g; 1-90 microg analyte can be easily eluted by 1-3 mL acetonitrile with an
      overall recovery of 98.2% and 78.3% for phenol and 1-naphthol, respectively.
      Linear correlation between acetonitrile solution absorbance (A(540)) and phenol
      concentration (C) in water was found according to the equation A(540) = (6 +/- 1)
      x 10(-2) + (0.9 +/- 0.1) C (micromol L(-1)) with a detection range from 1 x 10(
      8) mol L(-1) (0.9 microL g(-1)) to 2 x 10(-7) mol L(-1) (19 microL g(-1)), a
      limit of quantification of 1 microL g(-1) (preconcentration factor 125),
      correlation coefficient of 0.936, and relative standard deviation of 2.5%. A
      solid-phase colorimetric method was developed for quantitative determination of 1
      naphthol on adsorbent phase using scanner technology and RGB numerical analysis.
      The detection limit of 1-naphthol with this method is 6 microL g(-1) while the
      quantification limit is 20 microL g(-1). A test system was developed for naked
      eye monitoring of 1-naphthol impurities in water. The proposed test kit allows
      one to observe changes in the adsorbent color when 1-naphthol concentration in
      water is 0.08-3.2 mL g(-1).

PMID- 18322679
TI  - Visual information from the lower visual field is important for walking across
      multi-surface terrain.
AB  - Visual information concerning characteristics of the environment is critical for
      safe navigation. The purpose of this study was to determine the importance of
      vision from the lower visual field for negotiating multi-surface terrain. Ten
      healthy young adults and ten healthy older adults walked across a walkway where
      the middle portion consisted of solid, rock, slippery, compliant, tilt, and
      irregular surfaces (i.e. multi-surface terrain). Participants performed the
      walking trials with and without special glasses that blocked the lower visual
      field. Head pitch angle along with step parameters were measured. Young and older
      adults demonstrated increased mean and maximum head pitch angle downward when the
      lower visual field was blocked suggesting the importance of vision from this area
      when stepping on multi-surface terrain. In addition, young and older adults
      altered their gait pattern by reducing gait speed and step length when the lower
      visual field was blocked. These results suggest that information from the lower
      visual field is normally used when walking across multi-surface terrain. The
      results have implications for those individuals who wear multi-focal glasses and
      who use them while walking in complex environments, which may challenge balance.

PMID- 18322680
TI  - Genomic analysis of Ovis aries (Ovar) MHC class IIa loci.
AB  - Determining the genomic organization of the Ovis aries (Ovar) major
      histocompatibility complex class IIa region is essential for future functional
      studies related to antigen presentation. In this study, a bacterial artificial
      chromosome (BAC) library of genomic DNA from peripheral blood leukocytes (PBL) of
      a Rambouillet ram was constructed, and BAC clone consisting of the major
      histocompatibility complex (MHC) class II DQB2, DQA2, DQB1, DQA1, and DRB1 loci
      was identified and completely sequenced. The BAC clone consists of 160,889 bp of
      finished sequence with the loci arranged in the following order: DQB2, DQA2,
      DQB1, DQA1, and DRB1 with 14.3, 25, 6.6, and 40.9 Kb spanning between the loci,
      respectively. All five of these loci were transcribed in the animal used to
      generate the MHC class II BAC clone. Repeat or retrotransposable elements along
      with MHC class II cis promoter elements consisting of S, X, and Y boxes were
      identified in the sequence. In addition, 16 non-coding conserved sequences
      amongst primates, carnivores, and ruminants were identified (p < 0.001). These
      conserved sequences include binding sites for transcription factors with known
      roles in immune cells, and they provide a basis for further functional
      investigation of the genes in this region. This is the first ruminant finished
      sequence of the DQB2-DRB1 region, and this sequence information will aid in whole
      genome and transcriptome analyses of MHC class II.

PMID- 18322681
TI  - A systematic selection of the non-aqueous phase in a bacterial two liquid phase
      bioreactor treating alpha-pinene.
AB  - A systematic evaluation of the selection criteria of non-aqueous phases in two
      liquid phase bioreactors (TLPBs), also named two-phase partitioning bioreactors
      (TPPBs), was carried out using the biodegradation of alpha-pinene by Pseudomonas
      fluorescens NCIMB 11671 as a model process. A preliminary solvent screening was
      thus carried out among the most common non-aqueous phases reported in literature
      for volatile organic contaminants biodegradation in TLPBs: silicon oil, paraffin
      oil, hexadecane, diethyl sebacate, dibutyl-phtalate, FC 40, 1,1,1,3,5,5,5
      heptamethyltrisiloxane (HMS), and 2,2,4,4,6,8,8-heptamethylnonane (HMN). FC 40,
      silicone oil, HMS, and HMN were first selected based on its biocompatibility,
      resistance to microbial attack, and alpha-pinene mass transport characteristics.
      FC 40, HMS, HMN, and silicone oil at 10% (v/v) enhanced alpha-pinene mass
      transport from the gas to the liquid phase by a factor of 3.8, 14.8, 11.4, and
      8.6, respectively, compared to a single-phase aqueous system. FC 40 and HMN were
      finally compared for their ability to enhance alpha-pinene biodegradation in a
      mechanically agitated bioreactor. The use of FC 40 or HMN (both at 10% v/v)
      sustained non-steady state removal efficiencies (RE) and elimination capacities
      (EC) approximately 7 and 12 times higher than those achieved in the system
      without an organic phase, respectively. In addition, preliminary results showed
      that P fluorescens could uptake and mineralize alpha-pinene directly from the non
      aqueous phase.

PMID- 18322682
TI  - Dekkera and Brettanomyces growth and utilisation of hydroxycinnamic acids in
      synthetic media.
AB  - Dekkera and Brettanomyces yeast are important spoilage organisms in a number of
      food and beverage products. Isolates of both genera were cultured in a defined
      medium and supplemented with hydroxycinnamic acids and vinylphenols to
      investigate their influence on growth and the formation of ethyl phenol
      derivatives. The growth rate of Brettanomyces species in the presence of acids
      was reduced, and no significant conversion to vinyl or ethyl derivatives was
      observed. The growth rate and substrate utilisation rates of Dekkera anomala and
      Dekkera bruxellensis yeast differed depending on strain and the acid precursor
      present. Growth of D. bruxellensis was slowed by the presence of ferulic acid
      with the addition of 1 mM ferulic acid completely inhibiting growth. This study
      provides an insight into the spoilage potential of these organisms and possible
      control strategies involving hydroxycinnamic acids.

PMID- 18322683
TI  - Lung cancer patients' CD4(+) T cells are activated in vitro by MHC II cell-based
      vaccines despite the presence of myeloid-derived suppressor cells.
AB  - BACKGROUND: Advanced non-small cell lung cancer (NSCLC) remains an incurable
      disease. Immunotherapies that activate patients' T cells against resident tumor
      cells are being developed; however, these approaches may not be effective in
      NSCLC patients due to tumor-induced immune suppression. A major cause of immune
      suppression is myeloid-derived suppressor cells (MDSC). Because of the strategic
      role of CD4(+) T lymphocytes in the activation of cytotoxic CD8(+) T cells and
      immune memory, we are developing cell-based vaccines that activate tumor-specific
      CD4(+) T cells in the presence of MDSC. The vaccines are NSCLC cell lines
      transfected with costimulatory (CD80) plus major histocompatibility complex class
      II (MHC II) genes that are syngeneic to the recipient. The absence of invariant
      chain promotes the presentation of endogenously synthesized tumor antigens, and
      the activation of MHC II-restricted, tumor-antigen-specific CD4(+) T cells.
      METHODS: Potential vaccine efficacy was tested in vitro by priming and boosting
      peripheral blood mononuclear cells from ten NSCLC patients who had varying levels
      of MDSC. CD4(+) T cell activation was quantified by measuring Type 1 and Type 2
      cytokine release. RESULTS: The vaccines activated CD4(+) T cells from all ten
      patients, despite the presence of CD33(+)CD11b(+) MDSC. Activated CD4(+) T cells
      were specific for NSCLC and did not cross-react with tumor cells derived from non
      lung tissue or normal lung fibroblasts. CONCLUSIONS: The NSCLC vaccines activate
      tumor-specific CD4(+) T cells in the presence of potent immune suppression, and
      may be useful for the treatment of patients with NSCLC.

PMID- 18322684
TI  - Maturation of monocyte-derived dendritic cells with Toll-like receptor 3 and 7/8
      ligands combined with prostaglandin E2 results in high interleukin-12 production
      and cell migration.
AB  - Dendritic cells (DC) are professional antigen-presenting cells of the immune
      system that play a key role in regulating T cell-based immunity. In vivo, the
      capacity of DC to activate T cells depends on their ability to migrate to the T
      cell areas of lymph nodes as well as on their maturation state. Depending on
      their cytokine-secreting profile, DC are able to skew the immune response in a
      specific direction. In particular, IL-12p70 producing DC drive T cells towards a
      T helper 1 type response. A serious disadvantage of current clinical grade ex
      vivo generated monocyte-derived DC is the poor IL-12p70 production. We have
      investigated the effects of Toll-like receptor (TLR)-mediated maturation on ex
      vivo generated human monocyte-derived DC. We demonstrate that in contrast to
      cytokine-matured DC, DC matured with poly(I:C) (TLR3 ligand) and/or R848 (TLR7/8
      ligand) are able to produce vast amounts of IL-12p70, but exhibit a reduced
      migratory capacity. The addition of prostaglandin E2 (PGE2) improved the
      migratory capacity of TLR-ligand matured DC while maintaining their IL-12p70
      production upon T cell encounter. We propose a novel clinical grade maturation
      protocol in which TLR ligands poly(I:C) and R848 are combined with PGE2 to
      generate DC with both high migratory capacity and IL-12p70 production upon T cell
      encounter.

PMID- 18322685
TI  - Serum antibodies against Saccharomyces cerevisiae: a new prognostic indicator in
      metastatic renal-cell carcinoma.
AB  - PURPOSE: A recent study reported that a diet rich in bread and refined cereals
      might have an unfavorable role in the development of renal cell carcinoma (RCC).
      To test whether an underlying intolerance of bread ingredients is responsible for
      the unfavorable influence of bread on RCC, we examined patient sera for the
      presence of food-specific IgG. EXPERIMENTAL DESIGN: A commercial test was used to
      detect food-specific IgG directed against a panel of 113 food antigens in sera of
      54 patients with metastatic RCC. Kaplan-Meier estimates were used for univariate
      survival analysis, and differences in survival curves were assessed with the log
      rank test. Multivariate survival analysis was done using a Cox regression model.
      RESULTS: We found that RCC patients with elevated serum levels of IgG antibodies
      against S. cerevisiae, commonly known as baker's yeast and yet another bread
      component, have an unfavorable clinical course. Median survival of patients with
      high levels of S. cerevisiae IgG was only 17.8 months, whereas median survival of
      patients with low S. cerevisiae IgG was 43.8 months (P = 0.0022; log-rank).
      Multivariate survival analysis identified high levels of S. cerevisiae IgG as a
      strong and independent prognostic risk factor (risk ratio 4.6, P = 0.001; 95% CI
      1.61-13.08). CONCLUSIONS: Our findings indicate that serum levels of IgG against
      S. cerevisiae may predict survival in patients with metastatic RCC. The data
      suggest not cereals but baker's yeast being the critical component of bread that
      may cause immune deviation and impaired immunosurveillance in predisposed RCC
      patients.

PMID- 18322686
TI  - A phase I pharmacodynamic trial of bortezomib in combination with doxorubicin in
      patients with advanced cancer.
AB  - PURPOSE: This phase I trial sought to define the toxicity, maximally tolerated
      dose (MTD) and pharmacodynamics of a combination of bortezomib and doxorubicin in
      patients with advanced malignancies. PATIENTS AND METHODS: Twenty-six patients
      were treated with bortezomib intravenously on days 1, 4, 8 and 11, with
      doxorubicin also administered intravenously on days 1 and 8, both in a 21-day
      cycle. Dosing ranged from 1.0 mg/m(2) of bortezomib with 15 mg/m(2) of
      doxorubicin to 1.5 mg/m(2) of bortezomib with 20 mg/m(2) of doxorubicin.
      Pharmacodynamic studies performed included assessment of levels of 20S proteasome
      activity and ubiquitin-protein conjugates. RESULTS: The combination of bortezomib
      and doxorubicin was generally well tolerated. There were two dose limiting
      toxicities (DLT) at dose cohort 3 (1.3 mg/m(2) bortezomib, 20 mg/m(2)
      doxorubicin) and 2 DLT at dose cohort 3a (1.5 mg/m(2) bortezomib, 15 mg/m(2)
      doxorubicin). DLT seen included neutropenia, thrombocytopenia, and neuropathy. In
      addition, one patient developed grade 3 central nervous system toxicity in cycle
      2 (not a DLT). One patient with hormone refractory prostate cancer had a partial
      response. Proteasome inhibition in whole blood was demonstrated and an increase
      in ubiquitin-protein conjugates was observed in peripheral blood mononuclear
      cells of most patients. CONCLUSIONS: Bortezomib and doxorubicin can be
      administered safely. The recommended phase II dose for this 21-day cycle is
      bortezomib 1.3 mg/m(2 )intravenously on days 1, 4, 8 and 11, and doxorubicin 20
      mg/m(2) intravenously on days 1 and 8. This combination may be of special
      interest in multiple myeloma, given the activity of both drugs in that disease.

PMID- 18322687
TI  - [Solitary bone cysts of the pelvis. A frequently misinterpreted entity].
AB  - Solitary bone cyst of the pelvis is a rare lesion. The diagnosis is relatively
      simple providing sufficient material is accumulated during biopsy or surgery.
      Calcifying forms often cause difficulties in terms of differential diagnosis.
      Radiographic imaging can be complex when examining large lesions of the pelvis.
      Biopsy is the method of choice for definitive diagnosis, which should be verified
      against material gathered surgically or during curettage. Bone tumors of the
      pelvis have to be considered in the differential diagnosis of the lesion. Large
      cystic lesions of the pelvis in particular are to be reviewed pathohistologically
      to avoid false diagnosis. The consequences for the patient in terms of quality of
      life and life expectancy can be serious. The need for interdisciplinary
      cooperation is greater than ever to ensure correct diagnosis and therapy of bone
      lesions.

PMID- 18322688
TI  - Three-dimensional ultrasound (3D US) methods in the evaluation of calcular and
      non-calcular ureteric obstructive uropathy.
AB  - PURPOSE: To prospectively assess ureteric obstructive uropathy using three
      dimensional ultrasound (3D US) methods when the etiology of ureteral obstruction
      was proved difficult to evaluate with two-dimensional ultrasound (2D US) and
      plain radiography. METHODS: The study had the local Ethics Committee approval.
      All patients gave informed consent. 318 patients: 219 men and 99 women (including
      16 pregnant women) were selected within a 3-year period for 3D US based on
      clinical presentation, two dimensional ultrasound (2D US) results and preliminary
      plain radiography except for pregnant women. 3D US was performed on all patients.
      301 patients had further excretory urogram before intervention decisions.
      RESULTS: The study showed a high accuracy of detection of different levels of
      ureteric calcular obstruction; 99.1% in men and 96.7% in women. 3D XI technology
      proved more efficient in stone count (88.9%) than sectional planes and rendering
      method altogether (55.6%). The success rate of identifying obstructive uropathy
      due to inflammatory variants showed a perfect diagnostic value of 100%. Similar
      percentages could be obtained in cases secondary to neoplastic infiltration or
      permeation of the ureters. Cases compared with excretory urography revealed close
      correlation with 3D US and superiority of the latter when renal function
      physiologically altered in some cases of calcular obstructive uropathy.
      CONCLUSIONS: The 3D US methods in case of obstructive uropathy have proved to be
      useful as an easy, mobile and non-invasive diagnostic tool, improving 2D US
      diagnostic utility.

PMID- 18322689
TI  - Symptomatic Meckel's diverticulum in children: a 16-year review.
AB  - Meckel's diverticulum (MD) has varied presentations and often becomes a
      diagnostic challenge. The purpose of this study was to review the various
      presentations of symptomatic MD and to assess the sensitivity of the Meckel's
      scan as a diagnostic tool in patients with bleeding MD. The hospital records of
      71 consecutive patients with a diagnosis of MD from 1990 to 2005 were
      retrospectively reviewed. The data was assessed for age at presentation, sex,
      clinical features, investigations performed, surgical intervention and
      histopathological findings. There were 71 patients with a diagnosis of MD (age 2
      days-14 years). In eight patients, MD was an incidental finding at laparotomy.
      The remaining 63 patients were symptomatic and presented with various clinical
      features. Ten patients (15.8%) had clinical features of peritonitis; of these,
      six had perforated MD and four had Meckel's diverticulitis at laparotomy. Nine
      patients (14.2%) were diagnosed as intestinal obstruction, and at laparotomy, a
      Meckel's band was found to be the cause of the obstruction. Nine patients (14.2%)
      had a patent vitello-intestinal duct and presented with umbilical discharge.
      Thirty-five patients (55.5%) presented with episodes of bleeding per rectum or
      malaena. Ultrasound scans revealed intussusception in six patients requiring open
      reduction. Of the remaining 29 patients with bleeding per rectum, 27 underwent a
      Meckel's Tc99 scan that showed a positive tracer in 18 patients (66.6%) and
      negative in 9 (33.3%). All patients with a symptomatic MD underwent resection of
      the diverticulum. Histology revealed ectopic gastric mucosa in 43 patients
      (68.3%). MD has various presentations and can be easily misdiagnosed. It is
      necessary to maintain a high index of suspicion in the paediatric age group. The
      Meckel's scan has a poor positive predictive value and cannot be relied upon for
      a diagnosis in cases of bleeding MD if Tc99 scan is negative.

PMID- 18322690
TI  - Axillary nerve palsy after retrograde humeral nailing: clinical confirmation of
      an anatomical fear.
AB  - INTRODUCTION: Locked antegrade or retrograde nailing of humeral shaft and
      proximal humerus fractures is a well established treatment option. Anatomic
      morphological studies revealed a potential high risk of axillary nerve injury
      within proximal interlocking screw insertion. However, clinical experiences do
      not seem to confirm this, as there is a lack of interlocking screw insertion
      associated axillary lesions in literature. CASE REPORT: We report about a 69-year
      old man with a humeral shaft fracture (AO-type 12-A3) stabilized by a retrograde
      implanted interlocking nail. Proximal interlocking screw insertion was performed
      in a posterior-to-anterior direction. The fracture healed uneventfully. In a
      follow-up examination 2 years later, an atrophy and paralysis of the deltoid
      muscle were visible. Electrophysiological evaluation confirmed an isolated
      axillary nerve injury. Nevertheless, the patient showed good functional recovery
      with almost free range of motion. CONCLUSION: Even for clinical practise proximal
      interlocking screw insertion is associated with a substantial risk of axillary
      nerve injury. Particularly for posterior-to-anterior screw insertion anatomic
      conditions should be considered. In spite of axillary nerve lesion, recovery of
      almost full shoulder function is possible by compensating the loss of deltoid
      function by rotator cuff muscles.

PMID- 18322691
TI  - The effect of strontium ranelate on serum insulin like growth factor-1 and leptin
      levels in osteoporotic post-menopausal women: a prospective study.
AB  - OBJECTIVE: The aim of this study was to investigate the effects of strontium
      ranelate on insulin like growth factor-1 (IGF-1), leptin and osteocalcin levels
      in osteoporotic post-menopausal women. STUDY DESIGN: Thirty-three women were
      given 2 g/day strontium ranelate for 6 months. Serum IGF-1, leptin and
      osteocalcin levels were measured before and after the treatment. RESULTS:
      Strontium ranelate treatment increased IGF-1 levels significantly (P = 0.02).
      Leptin and osteocalcin levels did not change significantly before and after the
      treatment. There was no correlation between basal and 6-months treatment levels
      of IGF-1 and leptin. CONCLUSION: Strontium ranelate increases serum IGF-1 levels
      in osteoporotic post-menopausal women.

PMID- 18322692
TI  - Iodine-129 measurements in soil samples from Dolon village near the Semipalatinsk
      nuclear test site.
AB  - Dolon village, located about 60 km from the border of the Semipalatinsk nuclear
      test site, is known to be heavily contaminated by the first USSR atomic bomb test
      in August 1949. Soil samples around Dolon were taken in October 2005 in an
      attempt to evaluate internal thyroid dose arising from incorporation of
      radioiodine isotopes (mainly (131)I). Iodine-129 in soil was measured by using
      the technique of accelerator mass spectrometry. The (129)I/(127)I atom ratios
      measured were in the range from 3.3 x 10(-9) to 3.3 x 10(-7). These values were
      within the range of the current background level ( approximately 10(-9) to 10(
      7)) in the environment, including contributions from the global fallout of
      atmospheric nuclear tests and local fallout of nuclear facilities. The (129)I
      atom accumulated level in soil ranged from 1.28 x 10(13) to 1.59 x 10(14) atoms
      m(-2), the average (8.0 x 10(13)) of which was higher than the background level
      of (2-5) x 10(13). From the relationship between (129)I and( 137)Cs (corrected
      for background and decay from 1949 to 2005) accumulated levels, the background
      level of (129)I and the (129)I/(137)Cs ratio around Dolon were estimated to be
      (6.4 +/- 0.4) x 10(13) atoms m(-2) and 0.25 +/- 0.16, respectively. This
      (129)I/(137)Cs ratio is almost similar to the fission yield ratio for (239)Pu
      fast fission (0.24).

PMID- 18322693
TI  - Femtosecond-assisted diagnostic corneal biopsy (FAB) in keratitis.
AB  - BACKGROUND: Femtosecond laser technology (IntraLase, Irvine, CA, USA) has been
      introduced in corneal surgery, opening a new frontier and providing a new
      surgical modality. The purpose of this study is to present a series of patients
      with keratitis after Femtosecond-assisted diagnostic corneal biopsies (FAB).
      METHODS: Four patients with progressive keratitis--despite intensive broad
      spectrum topical antimicrobial therapy, or progressive stromal infiltration
      inaccessible to corneal scrapings--underwent femtosecond-assisted diagnostic
      corneal biopsy. A corneal specimen was obtained using the Femtosecond laser
      (IntraLase), including both clinically infected and adjacent non-infected clear
      corneal tissue. A combination of lamellar and keratoplasty treatment parameters
      were used. RESULTS: Corneal specimens of 3 mm diameter and 120 to 200 microm
      thickness were obtained in all patients. No intra- or early post-operative
      complications related to the procedure were found. In all patients, adequate
      specimens were submitted for cultures, smears, and permanent section staining.
      CONCLUSIONS: In this small case series of patients with undiagnosed keratitis,
      femtosecond-assisted diagnostic corneal biopsy (FAB) obtained adequate specimens
      without intra- or early post-operative complications, related to the procedure.

PMID- 18322694
TI  - Prolongation of heart allograft survival after long-term expression of soluble
      MHC class I antigens and vIL-10 in the liver by AAV-plasmid-mediated gene
      transfer.
AB  - INTRODUCTION: The essential prerequisite for successful gene therapy in vivo is
      an effective and long-lasting transfer of the desired gene into the respective
      cell type or tissue. Over the last decades, many different methods have been
      developed for this purpose. The use of plasmid DNA seems to be a good alternative
      to the commonly used viral vectors because its large-scale production is simple,
      and side effects are low. Unfortunately, most reports describe only short-term
      expression in vivo, probably due to the lack of genomic integration in the target
      cell. This problem can possibly be addressed by the use of adeno-associated virus
      plasmids (AAV plasmids), where the coding sequences are cloned between the AAV
      specific inverted terminal repeats. Here, we report our results after allogeneic
      heart transplantation, which followed AAV-plasmid-mediated gene transfer of the
      rat soluble major histocompatibility complex class I antigen RT1.A(a) and viral
      interleukin (vIL)-10 in the "high"-responder Dark Agouti to Lewis rat strain
      combination. RESULTS: A high and stable long-term expression was achieved by in
      vivo transfection of the liver using AAV plasmids. Serum levels over 1,000 ng/ml
      of soluble RT1.A(a) and over 300 pg of vIL-10, respectively, were achieved.
      Expression levels remained high for up to several months. A mean prolongation of
      heart allograft survival of 1 to 2 days was demonstrated after transfection of
      either RT1.A(a) or vIL-10.

PMID- 18322695
TI  - Prolene-Monocryl-composite meshes do not increase microvascular Staphylococcus
      aureus adherence and do not sensitize for leukocytic inflammation.
AB  - BACKGROUND AND AIMS: Mesh implantation for hernia repair bears the risk of
      bacterial mesh infection. In this study, we analyzed whether this complication is
      supported by an increased interaction of bacteria and leukocytes with the
      microvascular endothelium at the implantation site. MATERIALS AND METHODS:
      Ultrapro meshes were implanted into the dorsal skinfold chamber of Syrian golden
      hamsters. After 12 days, fluorescein isothiocyanate (FITC)-labeled staphylococci
      were injected in the animals. Subsequently, we analyzed bacterial adherence,
      leukocyte-endothelial cell interaction, and microhemodynamics in venules of the
      mesh border zone and of distant control tissue under baseline conditions and
      during TNF-alpha-induced inflammation using intravital fluorescence microscopy.
      The results were compared to animals which did not receive any bacteria. RESULTS:
      Under baseline conditions, leukocyte-endothelial cell interaction and bacterial
      adherence were not affected by the implanted biomaterial. TNF-alpha-induced
      inflammation significantly increased numbers of adherent leukocytes and bacteria
      in venules located in direct vicinity to the mesh however without any differences
      to control tissue. Comparable results were found for the leukocyte-endothelial
      cell interaction when animals were not exposed to bacteria. CONCLUSION: Implanted
      Ultrapro meshes do neither increase microvascular Staphylococcus aureus adherence
      nor sensitize for leukocytic inflammation. Thus, we suggest that a mesh-induced
      increase of bacterial adherence in vessels of the implantation site cannot be
      considered as a primary cause for the development of mesh infection.

PMID- 18322696
TI  - E-C coupling and contractile characteristics of mechanically skinned single
      fibres from young rats during rapid growth and maturation.
AB  - The postnatal growth of rats involves a developmental phase (0 to approximately 3
      weeks), a rapid growth phase ( approximately 3 to approximately 10 weeks), and a
      slower maturation phase ( approximately 10 weeks+). In this study, we
      investigated the age-related changes in excitation-contraction (E-C) coupling
      characteristics of mammalian skeletal muscle, during rapid growth (4-10 weeks)
      and maturation (10-21 weeks) phases, using single, mechanically skinned fibres
      from rat extensor digitorum longus (EDL) muscle. Fibres from rats aged 4 and 8
      weeks produced lower maximum T-system depolarization-induced force responses and
      fewer T-system depolarization-induced force responses to 75% run-down than those
      produced by fibres from rats aged 10 weeks and older. The sensitivity of the
      contractile apparatus to Ca(2+) in fibres from 4-week rats was significantly
      higher than that in fibres from 10-week rats; however, the maximum Ca(2+)
      activated force per skinned fibre cross-sectional area (specific force) developed
      by fibres from 4-week rats was on average approximately 44% lower than the values
      obtained for all the other age groups. In agreement with the age difference in
      specific force, the MHC content of EDL muscles from 4-week rats was approximately
      29% lower than that of 10-week rats. Thus, mechanically skinned fibres from rats
      undergoing rapid growth are less responsive to T-system depolarization and
      maximal Ca(2+) activation than fibres from rats at the later stage of maturation
      or adult rats. These results suggest that during the rapid growth phase in rats,
      the structure and function of elements involved in E-C coupling in fast-twitch
      skeletal muscle continue to undergo significant changes.

PMID- 18322698
TI  - Autopsy pathology should become a recognised subspecialty.

PMID- 18322697
TI  - Does contingency awareness mediate the influence of emotional learning on the
      cueing of visual attention?
AB  - Previous research has indicated that conditioning depends on contingency
      awareness (CA). However, we argue that these studies have examined this issue
      under methodological conditions that might be insensitive to associative learning
      without CA. In the present study we examined the effect of an experimental
      manipulation of CA on attentive processing of classically conditioned stimuli,
      which is sensitive to associative learning with and without CA. We found that
      aversive conditioning with additional contingency instructions modulated visual
      attention, in the sense that the conditioned cues captured and held attention
      more strongly than the non-conditioned cues. Surprisingly, conditioning under
      conditions of restricted CA yielded a response pattern that was different from
      that under full CA. These findings suggest that conditioning with full and
      restricted CA can lead to qualitatively different effects on attention.

PMID- 18322699
TI  - Airway clearance techniques to treat acute respiratory disorders in previously
      healthy children: where is the evidence?
AB  - Airway clearance techniques are an important part of the respiratory management
      in children with cystic fibrosis, bronchiectasis and neuromuscular disease. They
      are also, however, frequently prescribed in previously healthy children with an
      acute respiratory problem with the aim to speed up recovery. The current review
      explores the evidence behind this use of airway clearance techniques in children
      without underlying disease. Few studies have been performed; many different
      techniques are available and the therapies used are often poorly specified. It is
      necessary to name the specific airway clearance technique used in treatment
      rather than to just state "chest physiotherapy," a term that is often confused
      with chest clapping or vibration plus postural drainage. There is little evidence
      that airway clearance techniques play a role in the management of children with
      an acute respiratory problem. Physicians routinely prescribing airway clearance
      techniques in previously healthy children should question their practice.

PMID- 18322700
TI  - Giant cell tumor of bone: treatment and outcome of 214 cases.
AB  - BACKGROUND: Two hundred and fourteen patients with benign giant cell tumor of
      bone (GCTB), treated from 1980 to 2007 at the Department of Orthopedics of the
      University of Muenster (Germany), were analyzed in a retrospective study.
      PATIENTS AND METHODS: The mean age was 33.3 years with a female-to-male ratio of
      1.2 : 1. The mean follow up was 59.8 months. The recurrence rate of patients who
      received first treatment at our institution was 16.6%. The most common primary
      treatment was curettage (188 patients) usually followed by adjuvant local
      therapy. The effects of bone cement (PMMA), burring and hydrogen peroxide
      (H(2)O(2)) were statistically analyzed and the influence of a subchondral bone
      graft on the recurrence rate was evaluated. RESULTS: PMMA alone (n = 52) reduces
      the likelihood of recurrence by the factor 8.2, additional high-speed burring (n
      = 39) by the factor 3.9 (compared to PMMA only). H(2)O(2) (n = 42) seems to have
      an additional effect comparable to that of phenol although it did not reach
      statistical significance. CONCLUSION: The combination of all adjuncts (PMMA,
      burring, H(2)O(2) - n = 42) reduces the likelihood of recurrence by the factor
      28.2 compared to curettage only and therefore should be recommended as a standard
      treatment. If the tumor reaches close to the articulating surface a subchondral
      bone graft (n = 42) can be performed without risking a higher recurrence rate. We
      add seven cases of pulmonary metastases and two cases of multicentricity to the
      literature. Bisphosphonates and interferon alpha may have a beneficial effect.

PMID- 18322701
TI  - Evaluation of lower molecular mass (20-24 kDa) Taenia solium cysticercus antigen
      fraction by ELISA and dot blot for the serodiagnosis of neurocysticercosis in
      children.

PMID- 18322702
TI  - Pax6 3' deletion results in aniridia, autism and mental retardation.
AB  - The PAX6 gene is a transcription factor expressed early in development,
      predominantly in the eye, brain and gut. It is well known that mutations in PAX6
      may result in aniridia, Peter's anomaly and kertatisis. Here, we present mutation
      analysis of a patient with aniridia, autism and mental retardation. We identified
      and characterized a 1.3 Mb deletion that disrupts PAX6 transcriptional activity
      and deletes additional genes expressed in the brain. Our findings provide
      continued evidence for the role of PAX6 in neural phenotypes associated with
      aniridia.

PMID- 18322703
TI  - Differential gene expression of 36-kDa microfibril-associated glycoprotein (MAGP
      36/MFAP4) in rat organs.
AB  - By using quantitative Western blot analysis and the real time polymerase chain
      reaction technique, we investigated the differential gene expression of
      microfibril-associated glycoprotein (MAGP-36) in rat organs. The gene was
      expressed highly in sites rich in elastic fibers, such as aorta, skin, and
      esophagus. However, MAGP-36 was also expressed highly in some other sites
      containing no elastic fibers. In lung and trachea, the expression levels of MAGP
      36 mRNA were about seven times higher than those in other elastic tissues,
      although the protein abundances were almost at the same levels as other elastic
      tissues. MAGP-36 seemed to be secreted outside these organs. In brain, kidney,
      and spleen, although the expression levels of MAGP-36 mRNA were low, substantial
      amounts of MAGP-36 protein were detected. An immunohistochemical study revealed
      that MAGP-36 was present at the brush border of the S3 segment of proximal
      tubules in kidney. Since MAGP-36 is known to bind to mannan, MAGP-36 might be
      involved in mannose transport in the S3 segment. Thus, MAGP-36 might be
      multifunctional and present in a wide variety of sites in various organs.

PMID- 18322704
TI  - Inhibition of myoblast differentiation by Sfrp1 and Sfrp2.
AB  - Secreted Frizzled-related proteins (Sfrps) are extracellular regulators of Wnt
      signalling and play important roles in developmental and oncogenic processes.
      They are known to be upregulated in regenerating muscle and in myoblast cultures
      but their function is unknown. Here, we show that the addition of recombinant
      Sfrp1 or Sfrp2 to C2C12 cell line cultures or to primary cultures of satellite
      cells results in the inhibition of myotube formation with no significant effect
      on the cell cycle or apoptosis. Even though at confluence, treated and untreated
      cultures are identical in appearance, analyses have shown that, for maximum
      effect, the cells have to be treated while they are proliferating. Furthermore,
      removal of Sfrp from the culture medium during differentiation restores normal
      myotube formation. We conclude that Sfrp1 and Sfrp2 act to prevent myoblasts from
      entering the terminal differentiation process.

PMID- 18322705
TI  - Wavelet analysis of ecological time series.
AB  - Wavelet analysis is a powerful tool that is already in use throughout science and
      engineering. The versatility and attractiveness of the wavelet approach lie in
      its decomposition properties, principally its time-scale localization. It is
      especially relevant to the analysis of non-stationary systems, i.e., systems with
      short-lived transient components, like those observed in ecological systems.
      Here, we review the basic properties of the wavelet approach for time-series
      analysis from an ecological perspective. Wavelet decomposition offers several
      advantages that are discussed in this paper and illustrated by appropriate
      synthetic and ecological examples. Wavelet analysis is notably free from the
      assumption of stationarity that makes most methods unsuitable for many ecological
      time series. Wavelet analysis also permits analysis of the relationships between
      two signals, and it is especially appropriate for following gradual change in
      forcing by exogenous variables.

PMID- 18322706
TI  - Predator effects on prey population dynamics in open systems.
AB  - Animal population dynamics in open systems are affected not only by agents of
      mortality and the influence of species interactions on behavior and life
      histories, but also by dispersal and recruitment. We used an extensive data set
      to compare natural loss rates of two mayfly species that co-occur in high
      elevation streams varying in predation risk, and experience different abiotic
      conditions during larval development. Our goals were to generate hypotheses
      relating predation to variation in prey population dynamics and to evaluate
      alternative mechanisms to explain such variation. While neither loss rates nor
      abundance of the species that develops during snowmelt (Baetis bicaudatus) varied
      systematically with fish, loss rates of the species that develops during baseflow
      (Baetis B) were higher in streams containing brook trout than streams without
      fish; and surprisingly, larvae of this species were most abundant in trout
      streams. This counter-intuitive pattern could not be explained by a trophic
      cascade, because densities of intermediate predators (stoneflies) did not differ
      between fish and fishless streams and predation by trout on stoneflies was
      negligible. A statistical model estimated that higher recruitment and accelerated
      development enables Baetis B to maintain larger populations in trout streams
      despite higher mortality from predation. Experimental estimates suggested that
      predation by trout potentially accounts for natural losses of Baetis B, but not
      Baetis bicaudatus. Predation by stoneflies on Baetis is negligible in fish
      streams, but could make an important contribution to observed losses of both
      species in fishless streams. Non-predatory sources of loss were higher for B.
      bicaudatus in trout streams, and for Baetis B in fishless streams. We conclude
      that predation alone cannot explain variation in population dynamics of either
      species; and the relative importance of predation is species- and environment
      specific compared to non-predatory losses, such as other agents of mortality and
      non-consumptive effects of predators.

PMID- 18322707
TI  - Frequency of side effects in outpatient cancer care and their influence on
      patient satisfaction--a prospective survey using the PASQOC questionnaire.
AB  - STUDY OBJECTIVES: The aims of the study were to examine the frequency of side
      effects and fatigue in ambulatory cancer patients and to analyse how these
      symptoms are reflected in patient satisfaction. SETTING: Private practices (N =
      41) and day hospitals (N = 8) in Germany took part in the study. PARTICIPANTS:
      The respondents were 4,538 patients with cancer (response rate: 82%). The
      diagnoses were: 25% breast cancer, 21% colorectal cancer, 11% lymphomas and 12%
      haematological malignancies; mean age 63.5 years; 57% female. MEASUREMENTS: The
      2004 PASQOC questionnaire contained 63 problem-oriented items which covered
      patient satisfaction for 15 dimensions of care. One item specifically assessed
      the prevalence of 17 different side effects. A score reflecting the severity of
      fatigue (fatigue index) was computed from three additional questions. For
      statistical analysis of patient satisfaction, the problem frequency was computed
      for each item. RESULTS: The most frequent single side effects were fatigue (60%),
      hair loss (54%), nausea (51%), sleep disturbance (42%), weight loss (36%),
      diarrhoea (32%) and mouth ulcerations (31%). The mean number of side effects was
      5 per patient (range 0 to 17). The fatigue index revealed that 42% of subjects
      complained of moderate and 28% of severe fatigue. Both the total number of side
      effects and the fatigue score were negatively associated with patient
      satisfaction. CONCLUSIONS: Side effects and especially fatigue are frequent
      problems in cancer patients and are related to the patients' assessment of cancer
      care. Routine symptom assessment may identify patients who require more
      comprehensive supportive care.

PMID- 18322708
TI  - The symptom experience in the first 100 days following allogeneic hematopoietic
      stem cell transplantation (HSCT).
AB  - GOALS OF WORK: Despite advances in allogeneic hematopoietic stem cell
      transplantation (HSCT), post-transplant complications are common, and patients'
      symptom experience has not been well documented. PURPOSE: To characterize the
      symptom experience of adult patients pre-transplantation and days 0, 30, and 100
      after allogeneic HSCT. METHODS: Data from 76 participants enrolled in a
      prospective health-related quality of life (HRQL) study were used. Symptom
      occurrence, distress, and clusters were determined based on the 11 symptoms of
      the Symptom Distress Scale (SDS). RESULTS: Participants were on average 40 years
      old (SD +/- 13.5). The majority (54%) received reduced intensity conditioning.
      Prevalent symptoms included fatigue (68%) and worry (68%) at baseline, appetite
      change (88%) at day 0, and fatigue at days 30 (90%) and 100 (81%). Participants
      reported the following symptoms as severely distressing: worry (16%) [baseline],
      insomnia (32%) [day 0], appetite change (22%) [day 30], and fatigue (11%) [day
      100]. The total SDS score was highest at day 0 (M = 26.6 +/- 7.6) when the
      highest number of symptoms were reported [median = 8 (1-11)]. Symptoms formed
      clusters comprised of fatigue, appearance change, and worry at baseline, and
      fatigue, insomnia, and bowel changes at days 0 and 30. Compared to those with low
      symptom distress, participants with moderate/severe symptom distress reported
      poorer HRQL. CONCLUSION: Allogeneic HSCT patients present for transplantation
      with low symptom distress yet experience multiple symptoms and high symptom
      distress after HSCT conditioning. Understanding the symptom experience of
      allogeneic HSCT patients can guide management strategies and improve HRQL.

PMID- 18322709
TI  - Potent in vitro anti-Trypanosoma cruzi activity of pyridine-2-thiol N-oxide metal
      complexes having an inhibitory effect on parasite-specific fumarate reductase.
AB  - In the search for new therapeutic tools against Chagas disease (American
      trypanosomiasis) palladium and platinum complexes of the bioactive ligand
      pyridine-2-thiol N-oxide were exhaustively characterized and evaluated in vitro.
      Both complexes showed high in vitro growth inhibition activity (IC(50) values in
      the nanomolar range) against Trypanosoma cruzi, the causative agent of the
      disease. They were 39-115 times more active than the antitrypanosomal drug
      Nifurtimox. The palladium complex showed an approximately threefold enhancement
      of the activity compared with the parent compound. In addition, owing to their
      low unspecific cytotoxicity on mammalian cells, the complexes showed a highly
      selective antiparasite activity. To get an insight into the mechanism of action
      of these compounds, DNA, redox metabolism (intraparasite free-radical production)
      and two parasite-specific enzymes absent in the host, namely, trypanothione
      reductase and NADH-fumarate reductase, were evaluated as potential parasite
      targets. Additionally, the effect of metal coordination on the free radical
      scavenger capacity previously reported for the free ligand was studied. All the
      data strongly suggest that trypanocidal action of the complexes could mainly rely
      on the inhibition of the parasite-specific enzyme NADH-fumarate reductase.

PMID- 18322710
TI  - Comparison of the electronic properties, and thermodynamic and kinetic parameters
      of the aquation of selected platinum(II) derivatives with their anticancer IC50
      indexes.
AB  - Three potential anticancer agents {trans-[PtCl(2)(NH(3))(thiazole)], cis
      [PtCl(2)(NH(3))(piperidine)], and PtCl(2)(NH(3))(cyclohexylamine) (JM118)} were
      explored and compared with cisplatin and the inactive [PtCl(dien)](+) complex.
      Basic electronic properties, bonding and stabilization energies were determined,
      and thermodynamic and kinetic parameters for the aquation reaction were estimated
      at the B3LYP/6-311++G(2df,2pd) level of theory. Since the aquation process
      represents activation of these agents, the obtained rate constants were compared
      with the experimental IC(50) values for several tumor cells. Despite the fact
      that the processes in which these drugs are involved and the way in which they
      affect cells are very complex, some correlations can be deduced.

PMID- 18322711
TI  - A dynamic view of enzyme catalysis.
AB  - Recent experimental advances have shown that enzymes are flexible molecules, and
      point to a direct link between dynamics and catalysis. Movements span a wide time
      range, from nano- to milli-seconds. In this paper we introduce two aspects of
      enzyme flexibility that are treated with two appropriate techniques. First,
      transition path sampling is used to obtain an unbiased picture of the transition
      state ensemble in chorismate mutase, as well as its local flexibility and the
      energy flow during the chemical step. Second, we consider the binding and release
      of substrates in L-rhamnulose-1-phosphate aldolase. We have calculated the normal
      modes of the enzyme with the elastic network model. The lowest frequency modes
      generate active site deformations that change the coordination number of the
      catalytic zinc ion. The coordination lability of zinc allows the binding and
      release of substrates. Substitution of zinc by magnesium blocks the exchange of
      ligands.

PMID- 18322712
TI  - Is the early-onset torsion dystonia (EOTD) linked to TOR1A gene as frequent as
      expected in France?
AB  - Early onset torsion dystonia are rare movement disorders. Molecular defect is
      known for only a subgroup, consisting of a unique and recurrent mutation in the
      TOR1A gene. We undertook a nationwide census of French TOR1A-mutation carriers
      and the assessment of clinical associated signs. Overall, 53 index cases and 104
      relatives were studied and haplotypes linked to the mutation constructed. The
      previously reported Ashkenazi-Jewish haplotype was found in 11 families with the
      remainder carrying distinct haplotypes suggesting independent mutation events.
      This study demonstrates the scarcity of this disease in France with estimated
      disease frequency of 0.13:100,000 and mutation frequency of 0.17:100,000.

PMID- 18322713
TI  - Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV:
      demonstration of a founder mutation in the Turkish population.
AB  - Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital
      insensitivity to pain with anhidrosis, is an autosomal recessive disorder
      characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated
      sweat glands, and delayed mental and motor development. Mutations in the
      neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the
      neurotrophin signaling pathway phosphorylated in response to nerve growth factor,
      are associated with this disorder. We identified six families from Northern
      Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these
      families. Microsatellite and single nucleotide polymorphism (SNP) markers on the
      Affymetrix 250K chip platform were used to determine the haplotypes for three
      families harboring the same mutation. Screening for mutations in the NTRK1 gene
      demonstrated one novel frameshift mutation, two novel nonsense mutations, and
      three unrelated kindreds with the same splice-site mutation. Genotyping of the
      three families with the identical splice-site mutation revealed that they share
      the same haplotype. This report broadens the spectrum of mutations in NTRK1 that
      cause HSAN IV and demonstrates a founder mutation in the Turkish population.

PMID- 18322714
TI  - Evaluation of real-time polymerase chain reaction assays for the detection of
      herpes simplex virus in swab specimens.
AB  - An in-house herpes simplex virus (HSV) real-time polymerase chain reaction (PCR)
      hydrolysis probe assay and three commercial real-time HSV assays were evaluated
      for the detection of HSV from genital, oral, ocular and dermal clinical samples.
      Five hundred and sixty samples from patients displaying signs and symptoms of HSV
      infection were used to evaluate the in-house HSV assay. A representative 151
      samples were processed using the artus HSV-1/2 TM PCR Kit, SmartCycler Non-typing
      and SmartCycler Typing ASR kits. The in-house PCR assay demonstrated an overall
      positivity rate of 38% (211/560), equating to a 14% increase in HSV detection
      compared to 24% for culture (135/560). All 76 culture-negative, in-house PCR
      positive samples were confirmed using at least one HSV commercial kit. The in
      house, SmartCycler Non-typing, artus and SmartCycler Typing assays showed
      improved sensitivity (100%, 100%, 98% and 99%, respectively) compared to culture
      (37%), and all real-time assays were highly specific (100%). The in-house and
      commercial real-time HSV PCR assays performed well and, combined with careful
      clinical interpretation, should improve the detection, differentiation and
      quantification of HSV from mucocutaneous swab samples.

PMID- 18322715
TI  - Obesity pandemics and the modification of digestive bacterial flora.
AB  - Environmental factors, such as social networks, have an influence on obesity
      pandemics. The gut microbial flora (microbiota) plays a role in converting
      nutrients into calories. Variations in microbiota composition are found in obese
      humans and mice. The microbiota from an obese mouse confers an obese phenotype
      when transferred to an axenic mouse. There is a large body of experimental
      evidence and empirical data in the food industry showing that both antibiotics
      and probiotics, which modify the gut microbiota, can act as growth promoters,
      increasing the size and weight of animals. The current obesity pandemic may be
      caused, in part, by antibiotic treatments or colonization by probiotic bacteria.
      Using metagenomics and microarray analysis, studies of microbiota modifications
      after antibiotic and probiotic intake may identify the modifications associated
      with increased size and weight. Epidemiological studies recording these factors
      in an obese population may be able to link obesity with the absorption of
      microbiota modifiers.

PMID- 18322716
TI  - Therapeutic frontiers: preventing and treating infectious diseases by inhibiting
      bacterial quorum sensing.
AB  - Density-dependent cell-cell communication, or quorum sensing (QS), has been
      demonstrated in numerous species of bacteria. The basic function of QS is likely
      to confer a nutritional advantage, particularly in a highly populated, mixed
      species environment. QS also has ramifications on the production of colonization
      and virulence factors. Pheromone-like substances secreted into the extracellular
      milieu appear to govern many of the transcription products in these bacteria. At
      a high cell density, the QS systems are triggered, and the transcription of the
      colonization factors are suppressed and replaced by the expression of virulence
      factors. Major pathogens, such as Pseudomonas aeruginosa and Staphylococcus
      aureus, have evolved with numerous QS circuits, which modulate the production of
      various toxins and regulate parallel QS systems. Several QS-modulating therapies,
      such as macrolide antibiotics, QS vaccines, and competitive QS inhibitors, have
      been investigated and may prove to be helpful in diminishing the translation of
      QS-directed toxins or by prematurely activating the QS response to alert the
      immune system to bacteria hiding in a low cell density. QS represents a recently
      discovered method of bacterial communication and population control, which may
      prove to be a unique mechanism to prevent, suppress, and/or treat infectious
      diseases.

PMID- 18322717
TI  - Expression of a functional single-chain antibody via Corynebacterium
      pseudodiphtheriticum.
AB  - Antibody-based therapeutics are effective against conditions ranging from acute
      infections to malignancy. They may prove crucial in combating bioterrorism and
      responding to drug-resistant and emerging pathogens. At present the cost of
      producing therapeutic monoclonal antibodies is between $1,000 to $6,000 per gram.
      The need to administer antibodies parenterally at frequent intervals further
      drives the cost of this treatment. Here we present an antibody delivery system,
      termed paratransgenesis, with the potential to overcome these limitations. The
      paratransgenic approach involves genetically transforming a commensal or symbiont
      bacterium to express foreign molecules that target pathogens. We describe
      transformation of Corynebacterium pseudodiptheriticum, a commensal bacterium
      found in the human respiratory tract, to express a murine single-chain antibody
      binding progesterone. The antibody was functional and bound specifically to
      progesterone in a concentration-dependent manner. This marker antibody system is
      the precursor to development of expression systems producing recombinant
      humanized single-chain antibodies. Studies are in progress evaluating fitness,
      transgene stablility, and pathogenecity of the genetically engineered C.
      pseudodiptheriticum. We anticipate developing a repertoire of expressed molecules
      targeting infectious agents and surface epitopes of pulmonary mass lesions. If
      expression systems for anti-pathogen molecules in C. pseudodiptheriticum and
      other respiratory commensal bacteria can be optimized, these bacteria have the
      potential for a range of therapeutic and prophylactic applications.

PMID- 18322718
TI  - Endovascular stenting for the management of port-a-cath associated superior vena
      cava syndrome.
AB  - Port-a-cath systems are often essential for the administration of long-term
      chemotherapy in the treatment of malignancies because they improve venous access,
      but they are associated with complications, mainly thrombosis of central veins.
      In the present report, we describe a case of right subclavian and superior vena
      cava port-a-cath-related thrombosis causing superior vena cava syndrome (SVCS) in
      a patient affected by Hodgkin's disease. The patient underwent percutaneous
      revascularization with stent positioning, experiencing immediate relief of
      symptoms. Endovascular procedures for the treatment of nonmalignant SVCS seem to
      represent a challenging therapeutic option.

PMID- 18322719
TI  - Intra-sessional and inter-sessional variability of multifocal electroretinogram.
AB  - The aim of this study was to investigate the intra-sessional and inter-sessional
      variability of the multifocal electroretinogram (mfERG). Right eyes of 20 healthy
      adult subjects with uncorrected visual acuity of 1.0 were studied. mfERG
      recordings were obtained in two sessions by using jet corneal electrodes. The
      responses were averaged over five retinal regions, the central hexagon (CH: 0.0
      2.3 degrees ) and four concentric rings [ring 1 (R1: 2.3-7.4 degrees ), ring 2
      (R2: 7.4-12.0 degrees ), ring 3 (R3: 12.0-19.4 degrees ), and ring 4 (R4: 19.4
      30.0 degrees )]. In the first session, recordings were repeated while the
      electrodes stayed in place (the first and the second recordings). Second sessions
      (third recordings) were performed 1 week later. Individual coefficient of
      variation (CV; standard deviation/mean) for P1 and N1 amplitudes and implicit
      times were calculated for the first to second and first to third recordings to
      assess intra-sessional and inter-sessional variability, respectively, and were
      evaluated by Wilcoxon-paired samples test. Regarding implicit time and amplitude
      of mfERG recordings, there was no significant difference between the first to
      second and first to third recordings (P > 0.05, Bonferroni-corrected Wilcoxon
      test). CV values significantly decreased with eccentricity in both intra
      sessional and inter-sessional comparisons (P < 0.05, Wilcoxon test). However,
      partial ring averaging showed no significant difference (P > 0.05) between CV
      values for single hexagons in each ring. Intra-sessional CV values were
      significantly lower than corresponding inter-sessional values (P < 0.05, Wilcoxon
      test). Our results support the importance of electrode replacement on
      variability. The increased number of hexagons that are averaged is the main
      factor that explains the lower variability in the more peripheral rings.

PMID- 18322723
TI  - Ecotoxicological effects of buprofezin on fecundity, growth, development, and
      predation of the wolf spider Pirata piratoides (Schenkel).
AB  - The toxicological effects of buprofezin, an insect growth regulator, on the
      fecundity, development, and pest control potential of the wolf spider Pirata
      piratoides (Schenkel) (Araneae: Lycosidae) were investigated in the laboratory.
      It was shown that buprofezin had low toxicity to P. piratoides and that the
      median lethal dosage (LD(50)) 48 h and 10% lethal dosage (LD(10)) after topical
      application for female spiders were 653 and 316 mg buprofezin/mg fresh weight of
      spider, respectively. Buprofezin significantly reduced the percent hatching of
      spiders' eggs but had only a slight effect on egg production. No negative effects
      on the development and growth were observed. However, spider predation rates were
      strongly affected: Insecticide-treated females predated on fewer prey than the
      controls, and their predation rate did not recover even 5 days after insecticide
      application. This indicated that their pest control potential might be influenced
      by buprofezin, and the use of buprofezin in biological control of insects is
      discussed.

PMID- 18322720
TI  - [Social cognition in autism. A survey of functional imaging studies].
AB  - Autism spectrum disorders (autism, Asperger's syndrome, high-functioning autism)
      are characterized by a common pattern of marked impairments in social
      interactions. Deficits have been described in face processing, facial emotion
      recognition, and social attribution ("theory of mind") or generally speaking in
      social cognition. Some studies have shown that these impairments are already
      detectable in early childhood, leading to the assumption that the underlying
      cause is an early disruption of neuronal development. Accordingly, neuroimaging
      data have revealed alterations of structure and function in the brains of
      autistic children, adolescents, and adults. The present review gives a systematic
      overview of the existing literature on functional imaging studies using
      experimental paradigms of social cognition, i.e. face discrimination, facial
      emotion recognition, and theory of mind in autistic disorders.

PMID- 18322724
TI  - Changes in population, growth, and physiological indices of Longnose dace
      (Rhinichthys cataractae) in the Red Deer River, Alberta, Canada.
AB  - The Red Deer River, Alberta, Canada is a prairie river that is impacted by the
      point-source input of Red Deer's municipal wastewater effluent and non-point-
      source agricultural runoff. We used population, growth, and physiological
      performance end points in longnose dace (Rhinichthys cataractae), an endemic and
      abundant minnow, to evaluate changes in fish health over a 220 km section of the
      Red Deer River. Longnose dace immediately downstream of Red Deer had elevated
      catch per unit effort with larger body and liver sizes compared to upstream of
      Red Deer sites, likely due to elevated riverine productivity from Red Deer's
      wastewater effluent. Longnose dace immediately downstream of Red Deer showed
      depressed testosterone production capacity and elevated ethoxyresorufin-O
      deethylase (EROD) activity, which is consistent with exposure to endocrine
      disrupting compounds and aromatic hydrocarbons, respectively. Longnose dace 150
      180 km downstream of Red Deer had reduced liver and gonad sizes, elevated EROD,
      and increased 11-ketotestosterone production capacity compared to upstream of Red
      Deer sites, possibly related to a non-point-source agricultural influence on
      water quality. Longnose dace populations at the most downstream sites were
      missing the oldest age classes and might reach sexual maturity faster than at
      upstream sites, which is consistent with a younger age structure. Our results
      highlight the importance of assessing multiple performance end points to reveal
      physiological or reproductive effects in natural fish populations. We have
      demonstrated how longnose dace populations change over a river impacted by
      municipal wastewater and agricultural runoff; further studies are required to
      determine if these changes will influence the long-term viability of longnose
      dace in the Red Deer River.

PMID- 18322725
TI  - Toxicity assessment of the herbicides sulcotrione and mesotrione toward two
      reference environmental microorganisms: Tetrahymena pyriformis and Vibrio
      fischeri.
AB  - The potential toxicity of sulcotrione (2-[2-chloro-4-(methylsulfonyl)benzoyl]-1,3
      cyclohexanedione) and mesotrione (2-[4-(methylsulfonyl)-2-nitrobenzoyl]-1,3
      cyclohexanedione), two selective triketonic herbicides, was assessed using
      representative environmental microorganisms frequently used in ecotoxicology: the
      eukaryote Tetrahymena pyriformis and the prokaryote Vibrio fischeri. The aims
      were also to evaluate the toxicity of different known degradation products, to
      compare the toxicity of these herbicides with that of atrazine, and to assess the
      toxicity of the commercial herbicidal products Mikado and Callisto. Toxicity
      assays involved the Microtox test, the T. pyriformis population growth impairment
      test, and the T. pyriformis nonspecific esterase activity test. For each
      compound, we report original data (IC(50) values) on nontarget cells frequently
      used in ecotoxicology. Analytical standards sulcotrione and mesotrione showed no
      toxic effect on T. pyriformis population growth but a toxic influence was
      observed on nonspecific esterase activities of this microorganism and on
      metabolism of V. fischeri. Most of the degradation products studied and the two
      commercial formulations showed a greater toxicity than the parent molecules.
      Compared with the effect of atrazine, the toxicity of these triketonic herbicides
      was less than in T. pyriformis and greater than or the same as in V. fischeri.
      Additional work is needed to obtain a more accurate picture of the environmental
      impact of these herbicides. It will be necessary in future experiments to study
      the ecosystemic levels (aquatic and soil compartments) and to assess the
      potential toxicity of the newly discovered degradation products and of the
      additives accompanying the active ingredient in the commercial herbicidal
      formulations.

PMID- 18322726
TI  - Intrapericardial extralobar pulmonary sequestration presenting as a prenatal
      intrathoracic mass.
AB  - An intrathoracic mass, which persisted during the remaining pregnancy, was first
      seen during routine ultrasound examination performed at 20 weeks gestation. After
      birth, the child was asymptomatic. Echocardiography showed the mass to be located
      intrapericardially. The mass was electively resected via sternotomy 3 weeks after
      the birth. Microscopic examination showed normal lung tissue surrounded by pleura
      corresponding to the diagnosis of extralobar pulmonary sequestration. To the
      authors' knowledge, this is the earliest described detection of such a lesion.
      Furthermore, this article reports the unique finding of a feeding vessel from the
      right pulmonary artery.

PMID- 18322727
TI  - Fungal contamination of raw materials of some herbal drugs and recommendation of
      Cinnamomum camphora oil as herbal fungitoxicant.
AB  - The paper explores fungal infection and aflatoxin B1 contamination of six
      medicinal plant samples viz. Adhatoda vasica Nees, Asparagus racemosus Linn.,
      Evolvulus alsinoides Linn., Glycyrrhiza glabra Linn., Plumbago zeylanica Linn.
      and Terminalia chebula Retz. A total of 858 fungal isolates were detected from
      the raw materials. Maximum number of fungal isolates was detected from A.
      racemosus (228). The genus Aspergillus was found to be the most dominant genus
      causing infection to most of the raw materials. Among the 32 isolates of A.
      flavus tested, 13 isolates were found to be toxigenic elaborating aflatoxin B1.
      The highest elaboration of aflatoxin B1 was 394.95 ppb by the isolates of A.
      flavus from G. glabra. The essential oil of Cinnamomum camphora (L.) Presl showed
      efficacy in arresting aflatoxin B1 by the toxigenic strain. The growth of a
      toxigenic strain of A. flavus decreased progressively with increasing
      concentration of essential oil from leaves of C. camphora. The oil completely
      inhibited aflatoxin B1 production even at 750 ppm. Hence, the oil of C. camphora
      is recommended as herbal fungitoxicant against the fungal contamination of the
      raw materials.

PMID- 18322728
TI  - In vitro interactions between yeasts and bacteria and the fungal symbionts of the
      mountain pine beetle (Dendroctonus ponderosae).
AB  - Multi-trophic interactions between prokaryotes, unicellular eukaryotes, and
      ecologically intertwined metazoans are presumably common in nature, yet rarely
      described. The mountain pine beetle, Dendroctonus ponderosae, is associated with
      two filamentous fungi, Grosmannia clavigera and Ophiostoma montium. Other
      microbes, including yeasts and bacteria, are also present in the phloem, but it
      is not known whether they interact with the symbiotic fungi or the host beetle.
      To test whether such interactions occur, we performed a suite of in vitro assays.
      Overall, relative yield of O. montium grown with microbes isolated from larval
      galleries was significantly greater than when the fungus was grown alone.
      Conversely, the yield of G. clavigera grown with these same microbes was less
      than or equal to when it was grown alone, suggesting that O. montium, and at
      least some microbes in larval galleries, have a mutualistic or commensal
      relationship, while G. clavigera and those same microbes have an antagonistic
      relationship. A bacterium isolated from phloem not colonized by beetles was found
      to inhibit growth of both G. clavigera and O. montium and appears to be an
      antagonist to both fungi. Our results suggest that bacteria and yeasts likely
      influence the distribution of mycangial fungi in the host tree, which, in turn,
      may affect the fitness of D. ponderosae.

PMID- 18322729
TI  - Cultivation-based assessment of lysogeny among soil bacteria.
AB  - Lysogeny has long been proposed as an important long-term maintenance strategy
      for autochthonous soil bacteriophages (phages). Whole genome sequence data
      indicate that prophage-derived sequences pervade prokaryotic genomes, but the
      connection between inferred prophage sequence and an active temperate phage is
      tenuous. Thus, definitive evidence of phage production from lysogenic prokaryotes
      will be critical in determining the presence and extent of temperate phage
      diversity existing as prophage within bacterial genomes and within environmental
      contexts such as soils. This study optimized methods for systematic and
      definitive determination of lysogeny within a collection of autochthonous soil
      bacteria. Twenty bacterial isolates from a range of Delaware soil environments
      (five from each soil) were treated with the inducing agents mitomycin C (MC) or
      UV light. Six isolates (30%) carried inducible temperate phages as evidenced by
      an increase in virus direct counts. The magnitude of induction response was
      highly dependent upon specific induction conditions, and corresponding burst
      sizes ranged from 1 to 176. Treatment with MC for 30 min yielded the largest
      induction responses for three of the six lysogens. Morphological analysis
      revealed that four of the lysogens produced lambda-like Siphoviridae particles,
      whereas two produced Myoviridae particles. Additionally, pulsed-field gel
      electrophoresis data indicated that two of the six lysogens were polylysogens,
      producing more than one distinct type of phage particle. These results suggest
      that lysogeny is relatively common among soil bacteria.

PMID- 18322731
TI  - Diagnostic yield of computed tomography-guided coaxial core biopsy of
      undetermined masses in the free retroperitoneal space: single-center experience.
AB  - The purpose of this study was to evaluate the diagnostic yield of core biopsy in
      coaxial technique under guidance of computed tomography (CT) for retroperitoneal
      masses. We performed a retrospective analysis of CT-guided coaxial core biopsies
      of undetermined masses in the non-organ-bound retroperitoneal space in 49
      patients. In 37 cases a 15-G guidance needle with a 16-G semiautomated core
      biopsy system, and in 12 cases a 16-G guidance needle with an 18-G biopsy system,
      was used. All biopsies were technically successful. A small hematoma was seen in
      one case, but no relevant complication occurred. With the coaxial technique, up
      to 4 specimens were obtained from each lesion (mean, 2.8). Diagnostic accuracy in
      differentiation between malignant and benign diseases was 95.9%. A specific
      histological diagnosis could be established in 39 of 42 malignant lesions
      (92.9%). Correct subtyping of malignant lymphoma according to the WHO
      classification was possible in 87.0%. Benign lesions were correctly identified in
      seven cases, although a specific diagnosis could only be made in conjunction with
      clinical and radiological information. In conclusion, CT-guided coaxial core
      biopsy provides safe and accurate diagnosis of retroperitoneal masses. A specific
      histological diagnosis, which is essential for choosing the appropriate therapy,
      could be established in most cases of malignancy.

PMID- 18322732
TI  - Effect of biocides on biofilm bacteria from dental unit water lines.
AB  - Microbial biofilm formation in dental unit water lines (DUWL) is a phenomenon
      that has been recognized for nearly four decades. Water delivered by DUWL can
      harbor high numbers of bacteria, including opportunistic pathogens. Biofilms on
      tubing within DUWL may serve as a reservoir for these microorganisms and should
      therefore be controlled. In this study, the effects of eight biocides were
      monitored on DUWL biofilms individually and in combination by epifluorescence
      microscopy and total viable counts (TVC). The effects of sodium dodecyl sulphate
      (SDS), hydrogen peroxide (H2O2), sodium hypochlorite (NaOCl), phenol (Phe), Tween
      20 (Tw 20), ethylenediaminetetraacetic acid (EDTA), chlorohexidine gluconate
      (CHX), and povidine iodine (PI) were tested on DUWL biofilms alone and in
      combination. PI was found to have negligible effects on biofilm removal either
      applied alone or in combined form with CHX. Applying all biocides simultaneously
      did not completely eliminate viable bacteria nor did they remove biofilm.
      Overall, when combined, the biocides performed better than singly applied
      products. The most effective biocides were NaOCl and Phe (both alone and in
      combination).

PMID- 18322733
TI  - Characterization, identification, and cloning of the S-layer protein from
      Cytophaga sp.
AB  - We characterized, identified, and cloned a major protein which comprised 16% of
      the total proteins from Cytophaga sp. cell lysate. After French pressing, the
      fraction of cell envelope was treated with 0.2% Triton X-100 to remove cell
      membranes. Subsequent SDS-PAGE analysis of the Triton X-100-insoluble cell wall
      revealed a protein of 120 kDa with a pI of 5.4, which was identified by gold
      immunostaining as the surface (S)-layer protein of this soil bacterium. The
      nucleotide sequence of the cloned S-layer protein gene (slp) encoding this
      protein consisted of 3144 nucleotides with an ORF for 1047 amino acids, which
      included a typical 32-amino acid leader peptide sequence. Amino acid sequence
      alignment revealed 29-48% similarity between this protein and the S-layer
      proteins from other prokaryotic organisms. The 120-kDa protein from the Cytophaga
      sp. cell lysate has been characterized as a member of the S-layer proteins, and
      the slp gene was cloned and expressed in Escherichia coli. E. coli harboring the
      plasmid containing the 600- or 800-bp DNA fragment upstream of the initiation
      codon of the slp gene, in the presence of the reporter gene rsda (raw starch
      digesting amylase), showed amylase activity in starch containing plate. The
      putative promoter region of slp located 600 bp upstream of the initiation codon
      might be used for foreign gene expression.

PMID- 18322734
TI  - Trehalose-producing enzymes MTSase and MTHase in Anabaena 7120 under NaCl stress.
AB  - Salt tolerance, a multigenic trait, necessitates knowledge about biosynthesis and
      function of candidate gene(s) at the cellular level. Among the osmolytes,
      trehalose biosynthesis in cyanobacteria facing NaCl stress is little understood.
      Anabaena 7120 filaments exposed to 150 mM: NaCl fragmented and recovered on
      transfer to -NaCl medium with the increased heterocysts frequency (7%) over the
      control (4%). Cells failed to retain Na+ beyond a threshold [2.19 mM/cm3 (PCV)].
      Whereas NaCl-stressed cells exhibited a marginal rise in K+ (1.1-fold) only at 30
      h, for Na+ it was 130-fold at 48 h over cells in control. A time-course study (0
      54 h) revealed reduction in intracellular Na+ beyond 48 h [0.80 mM/cm3 (PCV)]
      suggestive of ion efflux. The NaCl-stressed cells showed differential expression
      of maltooligosyltrehalose synthase (MTSase; EC 5.4.99.15) and
      maltooligosyltrehalose trehalohydrolase (MTHase; EC 3.2.1.141) depending on the
      time and the extent of intracellular Na+ buildup.

PMID- 18322735
TI  - Laparoscopic management of complicated Meckel's diverticulum in children: a 10
      year review.
AB  - BACKGROUND: Meckel's diverticulum, the most common congenital anomaly of the
      gastrointestinal tract, is prone to develop complications in the pediatric
      population. The authors report their 10-year experience with the management of
      complicated Meckel's diverticulum in children using laparoscopy. METHODS: A
      retrospective review of all complicated Meckel's diverticulum cases involving
      children from 1998 to 2007 was performed. The efficacy and safety of laparoscopy
      used to manage complicated Meckel's diverticulum were assessed. RESULTS: Over a
      10-year period, 20 children (17 boys and 3 girls) with a mean age of 5 years
      (range, 7 months to 13 years) were included in the study. Of the 20 children, 12
      presented with gastrointestinal bleeding, 2 had intestinal obstruction, 3 had
      abdominal pain mimicking acute appendicitis, 2 had inguinal hernia, and 1 had
      intussusception. Diagnostic laparoscopy was performed for all the patients.
      Laparoscopically assisted transumbilical Meckel's diverticulectomy was performed
      successfully for 18 of the children. The operative time ranged from 50 to 190 min
      (mean, 115 min). All the children had an uneventful recovery except one, who
      experienced a postoperative wound infection. Ectopic gastric mucosa was found in
      14 cases. CONCLUSIONS: Diverse pediatric surgical conditions result from Meckel's
      diverticulum. Laparoscopy is a safe and effective method for the management of
      complicated Meckel's diverticulum.

PMID- 18322736
TI  - Laparoscopic pancreaticoduodenectomy is effective in a porcine model.
AB  - BACKGROUND: Laparoscopic pancreatic surgery is rapidly evolving due to improving
      instrumentation and surgical techniques. The challenges confronting laparoscopic
      pancreaticoduodenectomy (LPD), however, are its technical difficulty and its
      appropriateness for oncologic treatment. This study sought to develop a novel
      technique for LPD in an acute porcine model and to evaluate the safety and
      feasibility of LPD before clinical trials are undertaken. METHODS: The LPD
      procedure was performed in 10 pigs. Modified Child's reconstruction was performed
      intracorporeally. After the animals were killed, anastomotic sites were
      investigated by laparotomy. RESULTS: All the animals underwent LPD. The median
      operation time was 5 h, with minimal blood loss. One choledochojejunostomy had a
      small leak. CONCLUSIONS: The study proved LPD to be technically safe and feasible
      in an acute porcine model. Further studies and technical advances are necessary
      for transition of this clinical application of LPD to humans.

PMID- 18322737
TI  - Evaluation of sentinel lymph node metastasis alone guided by three-dimensional
      computed tomographic lymphography in video-assisted breast surgery.
AB  - BACKGROUND: Detailed relations between lymph nodes and lymph flow can be
      clarified by three-dimensional computed tomographic (3D-CT) lymphangiography.
      Systematic collection of lymph nodes based on 3D-CT lymphangiography can decrease
      unnecessary lymph node dissection and attendant complications. METHODS: To mark
      the sentinel lymph node (SLN) on the skin, 3D-CT lymphangiography was performed
      the day before the surgery. Iopamiron 300 (2 ml) was injected subcutaneously. A
      16-channel multidetector-row helical CT scan image was reconstructed to produce a
      3D image of lymph ducts and lymph nodes. Biopsy of SLN was performed by a dye
      staining method using Visiport-aided endoscopy. Stained lymph nodes were located
      by following the dye in the lymph ducts on a video monitor. For SLN-metastasis
      positive patients, standard axillary lymph node dissection (levels 1 and 2) was
      performed with video assistance. RESULTS: Since December 2001, video-assisted
      breast surgery has been performed for 180 patients, SLN biopsy for 150 patients,
      and 3D-CT lymphangiography for 110 patients. Findings show that SLN-positive
      metastasis (n = 31) was accompanied by SLN metastasis alone in 14 patients. One
      node metastasis, except for SLN, was observed in seven patients, two-node
      metastasis in three patients, and metastasis involving more than three nodes in
      seven patients. Review of the lymphoid path using 3D-CT lymphangiography
      confirmed that metastasis occurred in order of lymph flow. CONCLUSIONS: Absence
      of metastasis in the second and third SLNs, even in patients with SLN metastasis,
      obviates the need for dissection of more nodes.

PMID- 18322738
TI  - Laparoscopic gastric resection for gastrointestinal stromal tumors.
AB  - BACKGROUND: This study aimed to review clinical outcomes for patients selected to
      undergo laparoscopic resection for gastrointestinal stromal tumor (GIST) of the
      stomach. METHODS: All 112 laparoscopic gastric resections performed from February
      1995 to March 2007 were reviewed. Pre- and postoperative variables were analyzed,
      and data are given as mean +/- standard deviation. RESULTS: Laparoscopic gastric
      resection was attempted for 63 GIST in 61 patients (31 men and 30 women) with a
      mean age was 59.1 +/- 19 years. The tumors were located at the fundus (n = 19),
      antrum (n = 18), body (n = 17), gastroesophageal junction/cardia (n = 7), and
      pylorus (n = 2). Common presentations were upper gastrointestinal bleed (n = 29)
      and incidental finding on esophagogastroduodenoscopy (n = 17). The laparoscopic
      procedures performed were partial gastrectomy (n = 52), antrectomy (n = 4),
      esophagogastrectomy (n = 3), and endoscopically assisted and/or transgastric
      resection (n = 3). There was one conversion to open procedure for control of
      bleeding from the spleen. The mean tumor size was 3.8 +/- 1.8 cm. Negative
      surgical margins were achieved in all but one case. The mean operative time was
      151.9 +/- 67.3 min, and the mean estimated blood loss was 97.4 +/- 200.7 ml. A
      regular diet was resumed at a mean of 2.9 +/- 1.6 days, and the mean length of
      hospital stay was 3.9 +/- 2.2 days. The perioperative complication rate was 16.4%
      including deep vein thrombosis postoperative bleed, anastomotic stricture, and
      incisional hernia. One mortality occurred, due to respiratory failure. The GISTs
      included 48 rated as low risk, six rated as intermediate risk, and nine rated as
      high malignant potential. At a mean follow-up period of 15 +/- 21.8 months
      (range, 0-103 months), three of nine patients with high malignant potential GIST
      experienced, respectively, metastatic disease to the liver, liver and lung, and
      peritoneum. At this writing, all the other patients are disease free.
      CONCLUSIONS: Laparoscopic gastric resection for GIST is a feasible option.
      Adequate oncologic resection was achieved with 98.4% of patients chosen for
      laparoscopic resection. Resection margin positivity and recurrence rates are low
      after laparoscopic approaches for appropriately selected patients with GIST,
      demonstrating favorable characteristics.

PMID- 18322739
TI  - Minimally invasive video-assisted thyroidectomy and conventional thyroidectomy: a
      prospective randomized study.
AB  - BACKGROUND: Since the first description of the minimally invasive totally gasless
      video-assisted thyroidectomy (MIVAT) technique in 1998, relatively few studies
      have evaluated the outcome of this procedure. The authors review their
      experiences based on a prospective randomized trial comparing the potential
      advantages of MIVAT over conventional thyroidectomy. METHODS: Patients undergoing
      surgery for either thyroid nodule or diffuse thyroid disease with hyperthyroidism
      were randomly selected for either MIVAT or conventional thyroidectomy. The
      exclusion criteria specified nodules larger than 35 mm, thyroid lobe volume
      greater than 20 ml, thyroiditis, and previous neck irradiation or surgery.
      Operative time, postoperative complications, and cosmetic results were evaluated
      using both a verbal response scale and a numeric scale. RESULTS: Both the MIVAT
      group and the conventional thyroidectomy group included 15 patients. No
      significant differences were noted between the two groups in terms of age, sex,
      or indication for operation. The mean operative times were 65.5 +/- 18 min. for
      MIVAT and 43.3 +/- 14 min. for conventional thyroidectomy (P = 0.001). No
      postoperative complications were detected in either group. The cosmetic results,
      evaluated by both verbal response and numeric scales, were respectively as
      follows: MIVAT (3.7 +/- 0.2 and 7.9 +/- 1.2) and conventional thyroidectomy (2.3
      +/- 0.7 and 4.9 +/- 1.3). The differences significantly favored MIVAT (P = 0.028
      and P = 0.015, respectively) despite the small number of patients enrolled in
      this study, and consequently, its limited statistical power. CONCLUSION: Although
      the complications are comparable between the two approaches, conventional
      thyroidectomy involves less operative time. However, MIVAT offers distinct
      advantages to selected patients in terms of very good to exellent cosmetic
      results and reduced postoperative distress.

PMID- 18322740
TI  - Endoscopic water jets used to ablate Barrett's esophagus: preliminary results of
      a new technique.
AB  - BACKGROUND: The optimal management of Barrett's esophagus, a precursor to
      esophageal adenocarcinoma, remains controversial. Current therapy includes
      surveillance and ablative or resection techniques of varying safety and efficacy.
      This study aimed to determine the feasibility of a new catheter-based, endoscopic
      water jet ablation technique. METHODS: A high-pressure flexible catheter that can
      be passed through the working port of a standard gastroscope was used. The
      catheter had micro-drilled holes on one side near the tip. A 1-cm water jet was
      delivered under foot pedal control and endoscopic view at pressures adjusted from
      150 to 400 psi. After approval from the authors' Institutional Review Board,
      tissue segments from fresh esophagectomy specimens were ablated by the catheter
      without use of an endoscope. Using gross appearance and histologic analysis,
      variable ablation pressures and times were evaluated. RESULTS: Using variable
      pressures and times, 11 ablation sessions were performed: 5 for normal esophagus,
      4 for normal stomach, and 2 across the gastroesophageal junction in the setting
      of Barrett's esophagus. Ablation pressures of 150 to 300 psi for 30 to 60 s
      resulted in selective ablation of mucosa with preservation of the submucosa and
      muscularis propria. The depth of the ablation was determined by gross inspection
      at the time of ablation and confirmed by histologic evaluation. There was no
      embedding of epithelial cells in the muscularis propria. In a single normal
      esophagus specimen, a jet applied at 400 psi for 120 s in a confined area
      resulted in gross perforation. CONCLUSION: Selective ablation of esophageal and
      gastric epithelium using a catheter-based water jet ablation technique is
      feasible. The preliminary data from this study investigating a nonendoscopic
      technique show that the mucosa can be removed with preservation of the underlying
      submucosa and muscular layers. Further studies are warranted that focus on
      defining more precisely the pressure and duration required for optimal results
      and the practical application of this technique endoscopically.

PMID- 18322741
TI  - Does laparoscopic surgery decrease the risk of atrial fibrillation after foregut
      surgery?
AB  - BACKGROUND: Atrial fibrillation, which occurs in 12% of all major foregut
      surgeries, can prolong hospital stay and increase morbidity. Minimally invasive
      techniques in foregut surgery have been suggested to cause less tissue trauma. We
      examined the factors associated with new-onset atrial fibrillation after foregut
      surgery at our institution. METHODS: We retrospectively examined the records of
      154 adult patients who underwent major foregut surgery which included
      esophagectomy, partial or total gastrectomy, redo Heller myotomy, redo or
      transthoracic fundoplications. Univariate and multivariate logistic regression
      analysis with standard modeling techniques were performed to determine risk
      factors for new-onset atrial fibrillation. RESULTS: Of the 154 patients, 14
      patients developed new-onset atrial fibrillation with a higher mean age of 67.1
      years (+/-8.8 years) versus 56.4 years (+/-14.1 years) (p = 0.006). Laparoscopic
      (p = 0.004) and nonthoracic surgeries (p = 0.01) were associated with lower risk
      of atrial fibrillation. Patients with atrial fibrillation had received more fluid
      (6.5 +/- 2.8 liters versus 5.3 +/- 2.0 liters) and had longer operations (370 +/-
      103 min versus 362 +/- 142 min), none of which were statistically significant.
      The average intensive care length of stay of patients was longer: 7.5 +/- 6.8
      days versus 4.0 +/- 7.1 days (p = 0.004). Multivariate analysis revealed an
      association of atrial fibrillation with age (OR 1.08, 95% CI 1.02-1.14, p =
      0.01), and laparoscopic surgery (OR 0.09, 95% CI 0.01-0.95, p = 0.04) after
      adjusting for surgery type. CONCLUSIONS: Laparoscopic surgery is associated with
      lower risk of atrial fibrillation in foregut surgery. Development of atrial
      fibrillation is associated with increased length of intensive care stay. We
      recommend a prospective trial to confirm our findings.

PMID- 18322742
TI  - Laparoscopic blood-saving liver resection using a new radiofrequency-assisted
      device: preliminary report of an in vivo study with pig liver.
AB  - BACKGROUND: The aim of any device designed for liver resection is to allow blood
      saving and quick resections. This may be optimized using a minimally invasive
      approach. A radiofrequency-assisted device is described that combines a cooled
      blunt-tip electrode with a sharp blade on one side in an in vivo preliminary
      study using hand-assisted laparoscopy to perform partial hepatectomies. METHODS:
      Eight partial hepatectomies were performed on pigs with hand-assisted laparoscopy
      using the radiofrequency-assisted device as the only method for transection and
      hemostasis. The main outcome measures were transection time, blood loss,
      transection area, transection speed, blood loss per transection area, and tissue
      coagulation depth. The risk for biliary leak also was assessed using the
      methylene blue test. RESULTS: The transection time was 13 +/- 7 min for a mean
      transected area of 34 +/- 11 cm(2). The mean total blood loss was 26 +/- 34 ml.
      The mean transection speed was 3 +/- 1 cm(2)/min, and the blood loss per
      transection area was 1 +/- 1 ml/cm(2). Abdominal examination showed no
      complications in nearby organs. One biliary leak was identified in one case using
      the methylene blue test. The transection surface was 34 +/- 11 cm(2), and the
      mean tissue coagulation depth was 9 +/- 2 mm. The inviability of the coagulated
      surface was assessed by adenine dinucleotide (NADH) staining. CONCLUSIONS: The
      radiofrequency-assisted device has shown with a laparoscopic approach that it can
      perform liver resections faster and with less blood loss using a single device in
      a minimally invasive manner without vascular control than other commercial
      devices. The results show no significant differences with the same device used in
      an open procedure.

PMID- 18322743
TI  - A simplified laparoscopic ventral hernia repair: the scroll technique.
AB  - BACKGROUND: Laparoscopic ventral hernia repair has steadily gained recognition as
      an alternative to the open approach. However, the procedure can be technically
      challenging. The authors present their simple scroll technique for laparoscopic
      ventral hernia repair. METHODS: A total of 174 patients underwent laparoscopic
      ventral hernia repair using the scroll technique. The technique entails fixation
      of the rolled mesh to the anterior abdominal wall before it is unfolded. Patient
      characteristics, operative time, and complications were analyzed and compared
      with pooled data from the available literature on laparoscopic ventral hernia
      repair. RESULTS: The mean operative time was comparable with that reported by
      others (mean, 102 vs. 100 min). The hospital stay was shorter (mean, 1.8 vs. 2.4
      h). During a mean follow-up period of 28 months, the recurrence rate was lower
      than that reported by others (1.7% vs. 4.3%). There were no mortalities and no
      cases of inadvertent bowel injury. CONCLUSION: The authors' scroll technique for
      laparoscopic repair is simple, feasible, and reproducible, with a short learning
      curve and a low recurrence rate.

PMID- 18322744
TI  - Laparoscopic gastrectomy for gastric cancer: experience with more than 600 cases.
AB  - BACKGROUND: Among the less invasive operations noted in recent years,
      laparoscopic gastrectomy for gastric cancer has become popular because of
      advances in surgical techniques. The authors performed laparoscopic gastrectomy
      with regional lymph node dissection for 612 cases of gastric malignancies between
      March 1998 and August 2006. The technique and results of laparoscopic gastrectomy
      for gastric cancer are presented. METHODS: Of the 612 gastric malignancy cases,
      distal gastrectomy was performed in 485 cases, proximal gastrectomy in 42 cases,
      and total gastrectomy in 85 cases. In all the cases, D1 or D2 lymph node
      dissection was performed according to the general rule of the Japanese Gastric
      Cancer Association. RESULTS: Quicker recovery was observed in the laparoscopic
      gastrectomy cases than in the open cases. The postoperative complications with
      this technique were within a permissible range. No statistical difference was
      seen in the survival curve after surgery between the laparoscopic group of
      advanced cases preoperatively diagnosed as surgical T2N1 or lower and the open
      group. CONCLUSION: The laparoscopic technique is not only less invasive, but also
      similarly safe and curative compared with open gastrectomy.

PMID- 18322745
TI  - Incidence of residual choledocholithiasis detected by intraoperative
      cholangiography at the time of laparoscopic cholecystectomy in patients having
      undergone preoperative ERCP.
AB  - INTRODUCTION: The purpose of this study is to determine the incidence of residual
      common bile duct (CBD) stones after preoperative ERCP for choledocholithiasis and
      to evaluate the utility of routine intraoperative cholangiography (IOC) during
      laparoscopic cholecystectomy (LC) in this patient population. METHODS: All
      patients who underwent preoperative ERCP and interval LC with IOC from 5/96 to
      12/05 were reviewed under an Institutional Review Board (IRB)-approved protocol.
      Data collected included all radiologic imaging, laboratory values, clinical and
      pathologic diagnoses, and results of preoperative ERCP and LC with IOC. Standard
      statistical analyses were used with significance set at p < 0.05. RESULTS: A
      total of 227 patients (male:female 72:155, mean age 51.9 years) underwent
      preoperative ERCP for suspicion of choledocholithiasis. One hundred and eighteen
      patients were found to have CBD stones on preoperative ERCP, and of these, 22 had
      choledocholithiasis diagnosed on IOC during LC. However, two patients had
      residual stones on completion cholangiogram after ERCP and were considered to
      have retained stones. Therefore, 20 patients overall were diagnosed with either
      interval passage of stones into the CBD or a false-negative preoperative ERCP. In
      the 109 patients without CBD stones on preoperative ERCP, nine patients had CBD
      stones on IOC during LC, an 8.3% incidence of interval passage of stones or false
      negative preoperative ERCP. In both groups, there was no correlation (p > 0.05)
      between an increased incidence of CBD stones on IOC and a longer time interval
      between ERCP and LC, performance of sphincterotomy, incidence of cystic duct
      stones, or pathologic diagnosis of cholelithiasis. CONCLUSIONS: The overall
      incidence of retained or newly passed CBD stones on IOC during LC after a
      preoperative ERCP is 12.9%. Although the natural history of residual CBD stones
      after preoperative ERCP is not known, the routine use of IOC should be considered
      in patients with CBD stones on preoperative ERCP undergoing an interval LC.

PMID- 18322746
TI  - Multimedia article: Transvaginal laparoscopic cholecystectomy: laparoscopically
      assisted.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) is considered the new
      frontier for minimally invasive surgery. NOTES procedures such as peritoneoscopy,
      splenectomy, and cholecystectomy in animal models have been described. The aim of
      our experiment was to determine the feasibility and technical aspects of a new
      endoluminal surgical procedure. After approval from Columbia's IACUC, a
      transvaginal laparoscopically assisted endoscopic cholecystectomy was performed
      on four 30 kg Yorkshire pigs. The first step was to insert a 1.5 cm endoscope
      into the vagina under direct laparoscopic vision. Then the gallbladder was
      reached and, with the help of a laparoscopic grasper to hold up the gallbladder,
      the operation was performed. At the end of the procedure the gallbladder was
      snared out through the vagina attached to the endoscope. There were no
      intraoperative complications such as bleeding, common bile duct or endo-abdominal
      organ damage. Total operative time ranged between 110 and 155 min. Based on our
      experience in the porcine model, we believe that a transvaginal endoscopic
      cholecystectomy is feasible in humans.

PMID- 18322747
TI  - A new approach to hand-assisted laparoscopic liver surgery.
AB  - BACKGROUND: The best type of laparoscopic approach in solid liver tumours (SLTs),
      whether total laparoscopic surgery or hand-assisted laparoscopic surgery (HALS),
      has not yet been established. Our objective is to present our experience with
      laparoscopic liver resections in SLTs performed by HALS using a new approach.
      METHODS: We performed 35 laparoscopic resections in SLTs, of which 26 were
      carried out using HALS (in 25 patients) and 21 patients had liver metastases of a
      colorectal origin (LMCRC) (1 patient had 2 resections), 1 metastasis from a
      neuroendocrine tumour of the pancreas, 1 hepatocarcinoma on a healthy liver, 1
      primary hepatic leiomyosarcoma and 1 giant haemangioma. Mean follow-up was 22
      months. OPERATION: One right hemihepatectomy, one left hemihepatectomy, five
      bisegmentectomies II-III, three bisegmentectomies VI-VII and 16 segmentectomies
      (five of S. VI, three of S. VIII; three of S. V; two of S. IVb; one of S. II; one
      of S. IV; and in the remaining case resection of S. III and VI plus resection of
      a metastasis in S. VIII). MAIN OUTCOME MEASURES: Morbidity and mortality,
      conversion to open procedure, intraoperative blood loss, intra- and postoperative
      transfusion, length of stay and survival. RESULTS: There were no intra- or
      postoperative deaths, nor were there any conversions. One patient presented with
      morbidity (3.8%) (liver abscess). Mean blood loss was 200 ml (range 0-600 ml).
      One patient required transfusion (3.8%). Mean operative time was 180 min (range
      120-360 min). Mean length of hospital stay was 4 days (range 2-5 days). The
      actuarial survival rate of the patients at 36 months with liver metastases from
      colorectal carcinoma (LMCRC) was 80%. CONCLUSIONS: Liver resection with HALS
      reproduces the low morbidity and mortality rates and effectiveness (3-year
      survival) of open surgery in SLTs when indicated selectively.

PMID- 18322748
TI  - Pitfalls related to the use of endostaplers during video-assisted thoracic
      surgery.
AB  - BACKGROUND: The use of staplers during thoracoscopic pulmonary resections has
      entailed several incidents. This study aimed to evaluate the rate of adverse
      events related to the use of an endostapler during video-assisted thoracic
      surgery (VATS). METHODS: All thoracoscopic procedures involving the use of an
      endostapler were prospectively studied. The study was based on the analysis of
      data prospectively entered into a database and the review of videotapes recorded
      during the procedure. The video clip of each incident was included into the
      database. The following events were recorded: oozing or hemorrhage on the staple
      line, partial or total disruption of the staple line, and any other technical
      issue. RESULTS: A total of 434 firings were made during 130 thoracoscopic
      operations. The operations involved 77 wedge resections of lung nodules, 11
      pulmonary biopsies, 34 bullectomies, and 8 thoracoscopic lobectomies. Although
      firing was uneventful for most patients, a minor or major problem was encountered
      during 34 firings (7.6%). Two technical malfunctions of the device occurred, both
      of them noticed by the scrub nurse before introduction of the stapler into the
      trocar. The other pitfalls were oozing (13 cases) and active hemorrhages (5
      cases) on the staple line and disruption of the staple line, either partial (13
      cases) or total (1 case). Conversion to thoracotomy was never necessary. Whereas
      no specific action was imposed by the pitfall in 12 cases, the incident led to a
      repair in 22 cases. None of the incidents had a clinical consequence in the
      postoperative course. The video tapes were reviewed to check whether the accident
      was unpredictable or due the surgeon's misuse or misjudgment. In 14 cases, no
      cause was found. In 5 cases, the lung parenchyma probably was too thick for the
      staples chosen, whereas no technical error was found in the remaining 15 cases.
      CONCLUSION: Although some adverse events are attributable to surgical errors,
      many are linked to the device. This underscores the need for improving staplers
      and evaluating new technologies.

PMID- 18322749
TI  - Cine-MRI detection of intraabdominal adhesions: correlation with intraoperative
      findings in 89 consecutive cases.
AB  - BACKGROUND: This study aimed to evaluate the accuracy of functional cine-MRI in
      detecting abdominal adhesions. METHODS: For this study, 89 consecutive patients
      with adhesion-related complaints after previous abdominal surgery underwent
      preoperative workup including cine-MRI in transverse and sagittal orientations
      for a dynamic examination of an induced visceral slide. An abdominal map
      consisting of nine segments was created to document the location and extent of
      the adhesion. Cine-MRI and intraoperative findings were correlated. RESULTS: A
      total of 59 laparotomies and 30 laparoscopies were performed. Four cases required
      open surgery due to severe adhesions. The use of cine-MRI scan for the detection
      of adhesions showed an overall accuracy of 90%, a sensitivity of 93%, and a
      positive predictive value of 96%. The stronger the adhesions, the more accurate
      the scan findings. Of 44 patients with second-degree MRI scan findings, 50% had
      second-degree intraoperative findings. Of 35 patients with third- and fourth
      degree adhesions on MRI scans, 74% had exactly the same intraabdominal findings
      at surgery. The MRI scan showed adhesions located in the small intestines (75%),
      large intestines (35%), abdominal cavity (42%), and reproductive organs (32%).
      Intraoperatively, adhesions were found in the small intestines (70%), large
      intestines (40%), abdominal cavity (42%), and reproductive organs (28%).
      CONCLUSIONS: Cine-MRI provides valid preoperative information with respect to
      extent, location, and strength of intraabdominal adhesions. Cine-MRI is a good
      alternative for diagnosing abdominal adhesions because objective findings of the
      scan and intraoperative findings correlate very well with each other.

PMID- 18322750
TI  - Hybrid cytomegalovirus-U6 promoter-based plasmid vectors improve efficiency of
      RNA interference in zebrafish.
AB  - Short hairpin RNA (shRNA) directed by RNA polymerase III (Pol III) or Pol II
      promoter was shown to be capable of silencing gene expression, which should
      permit analyses of gene functions or as a potential therapeutic tool. However,
      the inhibitory effect of shRNA remains problematic in fish. We demonstrated that
      silencing efficiency by shRNA produced from the hybrid construct composed of the
      CMV enhancer or entire CMV promoter placed immediately upstream of a U6 promoter.
      When tested the exogenous gene, silencing of an enhanced green fluorescent
      protein (EGFP) target gene was 89.18 +/- 5.06% for CMVE-U6 promoter group and
      88.26 +/- 6.46% for CMV-U6 promoter group. To test the hybrid promoters driving
      shRNA efficiency against an endogenous gene, we used shRNA against no tail (NTL)
      gene. When vectorized in the zebrafish, the hybrid constructs strongly repressed
      NTL gene expression. The NTL phenotype occupied 52.09 +/- 3.06% and 51.56 +/-
      3.68% for CMVE-U6 promoter and CMV-U6 promoter groups, respectively. The NTL gene
      expression reduced 82.17 +/- 2.96% for CMVE-U6 promoter group and 83.06 +/- 2.38%
      for CMV-U6 promoter group. We concluded that the CMV enhancer or entire CMV
      promoter locating upstream of the U6-promoter could significantly improve
      inhibitory effect induced by the shRNA for both exogenous and endogenous genes
      compared with the CMV promoter or U6 promoter alone. In contrast, the two hybrid
      promoter constructs had similar effects on driving shRNA.

PMID- 18322751
TI  - Computer-aided prostate cancer detection using texture features and clinical
      features in ultrasound image.
AB  - In this paper, we propose a new prostate detection method using multiresolution
      autocorrelation texture features and clinical features such as location and shape
      of tumor. With the proposed method, we can detect cancerous tissues efficiently
      with high specificity (about 90-95%)and high sensitivity (about 92-96%) by the
      measurement of the number of correctly classified pixels. Multiresolution
      autocorrelation can detect cancerous tissues efficiently, and clinical knowledge
      helps to discriminate the cancer region by location and shape of the region and
      increases specificity. The support vector machine is used to classify tissues
      based on those features. The proposed method will be helpful in formulating a
      more reliable diagnosis, increasing diagnosis efficiency.

PMID- 18322753
TI  - Identification of patients with high-risk stage II colon cancer for adjuvant
      therapy.
AB  - PURPOSE: Adjuvant therapy for Stage II colon cancer remains controversial but may
      be considered for patients with high-risk features. The purpose of this study was
      to assess the prognostic significance of commonly reported clinicopathologic
      features of Stage II colon cancer to identify high-risk patients. METHODS: We
      analyzed a prospectively maintained database of patients with colon cancer who
      underwent surgical treatment from 1990 to 2001 at a single specialty center. We
      identified 448 patients with Stage II colon cancer who had been treated by
      curative resection alone, without postoperative chemotherapy. RESULTS: With
      median follow-up of 53 months, 5-year disease-specific survival for this cohort
      was 91 percent. Univariate and multivariate analyses identified three independent
      features that significantly affected disease-specific survival: tumor Stage T4
      (hazard ratio (HR), 2.7; 95 percent confidence interval (CI), 1.1-6.2; P = 0.02),
      preoperative carcinoembryonic antigen > 5 ng/ml (HR, 2.1; 95 percent CI, 1.1-4.1;
      P = 0.02), and presence of lymphovascular or perineural invasion (HR, 2.1; 95
      percent CI, 1-4.4; P = 0.04). Five-year disease-specific survival for patients
      without any of the above poor prognostic features was 95 percent; five-year
      disease-specific survival for patients with one of these poor prognostic features
      was 85 percent; and five-year disease-specific survival for patients with > or =
      2 poor prognostic features was 57 percent. CONCLUSIONS: Patients with Stage II
      colon cancer generally have an excellent prognosis. However, the presence of
      multiple adverse prognostic factors identifies a high-risk subgroup. Use of
      commonly reported clinicopathologic features accurately stratifies Stage II colon
      cancer by disease-specific survival. Those identified as high-risk patients can
      be considered for adjuvant chemotherapy and/or enrollment in investigational
      trials.

PMID- 18322754
TI  - Therapeutic efficacy of infliximab on patients with short duration of Crohn's
      disease: a Japanese multicenter survey.
AB  - PURPOSE: This study was designed to evaluate the efficacy of infliximab in
      patients with Crohn's disease of durations less than one year. METHODS: Two
      nationwide surveys of 35 Japanese institutions majoring in inflammatory bowel
      disease identified 41 patients with active Crohn's disease who were treated by
      infliximab within 12 months after the diagnosis (E-group) and 97 patients treated
      later during their clinical course (L-group). Clinical features, responses to
      infliximab, and accompanying medications were compared between the two groups. A
      decrease in Crohn's disease activity index > or = 70 or the index < 150 two weeks
      after infliximab was regarded to be efficacious. RESULTS: The age was younger (24
      vs. 33 years, median, P < 0.0001) and intestinal stricture (12 vs. 49 percent, P
      < 0.0001), internal fistula (0 vs. 26 percent, P = 0.0003), and previous
      intestinal resection (7 vs. 57 percent, P < 0.0001) were less frequent in the E
      group than in the L-group. The efficacy of infliximab was different between the
      two groups with a significantly higher value in the E-group than in the L-group
      (90 vs. 61 percent, P = 0.0012). A multivariate logistic regression analysis
      revealed nonstricturing intestinal lesion to be a significant factor related to
      the efficacy of infliximab. CONCLUSION: Infliximab is more efficacious in Crohn's
      disease with short duration, probably because of less frequent stenosis.

PMID- 18322755
TI  - Adenoma detection rate and the quality of colonoscopy: the sword has two edges.
AB  - With the increasing demand for colonoscopy for colorectal cancer screening and
      surveillance of colorectal adenomas and carcinomas, there has been an increasing
      emphasis on the quality of colonoscopy. Few publications have considered the full
      implications of pushing the adenoma detection rate as a prime quality indicator.
      In this article, some of the potential problems with this course are discussed
      and an alternative approach is suggested. Although defining and measuring quality
      in colonoscopy is important, further work needs to be done to arrive at a
      practical, clinically meaningful way of quality assessment.

PMID- 18322756
TI  - A desmoid tumor-staging system separates patients with intra-abdominal, familial
      adenomatous polyposis-associated desmoid disease by behavior and prognosis.
AB  - PURPOSE: Intra-abdominal desmoid tumors associated with familial adenomatous
      polyposis are heterogeneous. A recent staging system categorizes desmoids
      according to size, symptoms, and complications. We applied the staging system to
      determine whether it separates patients into clinically significant groups.
      METHODS: The staging system was applied to 101 patients with familial adenomatous
      polyposis. RESULTS: There were 21 patients with Stage I tumors, 36 with Stage II,
      26 with Stage III, and 18 with Stage IV. Twelve patients with Stage I and five
      with Stage II tumors needed no treatment. Eight patients with Stage I disease
      received medical treatment, as did 26 with Stage II, 16 with Stage III, and 15
      with Stage IV. Six Stage I tumors had surgery, as did 20 Stage II, 12 Stage III,
      and 13 Stage IV. Chemotherapy was given to 1 Stage II tumor, 7 Stage III, and 5
      Stage IV. No patient with Stages I or II disease died. Four Stage III patients
      (15 percent) and 8 Stage IV patients (44 percent) died from desmoids. Finally 89
      percent with Stage I, 65 percent with Stage II, 59 percent with Stage III, and 50
      percent with Stage IV disease were asymptomatic; 81 percent of Stage I desmoids,
      78 percent of Stage II, 42 percent of Stage III, and 28 percent of Stage IV were
      stable or disappeared. CONCLUSION: Desmoid staging identifies tumors by prognosis
      and its use for designing prospective treatment studies is reasonable.

PMID- 18322757
TI  - Sacral nerve stimulation in patients with severe constipation.
AB  - PURPOSE: Constipation is frequently a multifactorial disease. This study was
      designed to evaluate the potential effects of sacral nerve stimulation for
      patients suffering from severe chronic constipation. METHODS: Nineteen patients
      suffering from pathologic colonic transit time or rectal outlet obstruction were
      included. Only patients with severe rectal outlet obstruction who needed digital
      manipulation for defecation or patients suffering from pathologic colonic transit
      constipation with less than two bowel movements per week were regarded as
      candidates. A temporary stimulation lead was implanted into the sacral foramen
      that showed the best muscular response. After an evaluation period, the
      stimulation electrode was removed. An improvement in constipation (more than 2
      bowel movements per week or defecation without digital manipulation,
      respectively) during the test stimulation, as well as a recurrence of
      prestimulation constipation symptoms during the following surveillance period of
      three weeks were prerequisites for implanting the permanent sacral nerve
      stimulating system. RESULTS: All of the patients showed a positive motor response
      to acute needle stimulation. After the evaluation period, eight patients (42
      percent) reported an improvement of constipation, and permanent systems were
      implanted successfully. During the median follow-up of 11 (range, 2-20) months, a
      significant improvement in the Wexner constipation score was observed compared
      with the preoperative baseline level (baseline: median: 23, range, 18-27; 12
      months after implantation: median, 8, range, 4-13). After successful sacral nerve
      stimulation, patients also showed a significant improvement in their quality of
      life. CONCLUSIONS: Patients suffering from severe constipation are a new
      challenge for sacral nerve stimulation but further research on pelvic floor
      function is needed.

PMID- 18322758
TI  - Use of the sentinel node procedure to stage endometrial cancer.
AB  - BACKGROUND: Lymph node status is a major prognostic factor and a criterion for
      adjuvant therapy in endometrial cancer. The sentinel lymph node (SN) procedure
      has emerged as a possible alternative to systematic lymphadenectomy. The aims of
      this study were to determine the detection rate and the false-negative rate of
      the SN procedure, and its contribution to the staging of women with endometrial
      cancer. METHODS: Forty-six patients with endometrial cancer underwent the
      sentinel node procedure followed by pelvic lymphadenectomy. SNs were detected
      with a dual or single labelling method in 39 and 7 cases, respectively. All SNs
      were analysed by both hematoxylin and eosin (H&E) staining and immunochemistry.
      RESULTS: SNs were identified in 40 patients (87%), whose mean number of SN was
      2.6 (range 1-5). The SN detection rate was significantly lower with the single
      label than with the dual label (p = 0.01). Ten women (25%) had a positive SN on
      final histology (i.e. there were no false negatives). A correlation was observed
      between lymph node involvement and both histological grade (p = 0.01) and
      lymphovascular space involvement (p = 0.001). The stage predicted by magnetic
      resonance (MR) imaging correlated poorly with the Federation International of
      Gynaecology and Obstetrics (FIGO) stage. Among the ten women with a positive SN,
      three of the four women with a grade 1 tumour at biopsy had grade 2-3 disease on
      final histology. Seven of the ten women with a positive SN underwent external
      pelvic radiotherapy, based solely on their SN involvement. CONCLUSION: The SN
      procedure can reliably determine lymph node status in women with endometrial
      cancer. Given the limited capacity of MR imaging to detect myometrial invasion,
      and of biopsy to determine histological grade, our results support the systematic
      use of the SN procedure in women with endometrial cancer, including those with
      presumed early-stage disease and/or well-differentiated tumours.

PMID- 18322759
TI  - Intramammary sentinel lymph nodes: what is the clinical significance?

PMID- 18322760
TI  - Discussing weight with obese primary care patients: physician and patient
      perceptions.
AB  - OBJECTIVE: To evaluate patient-provider agreement on whether weight and related
      behaviors were discussed during routine visits. DESIGN: Post-visit survey
      assessments of patients and providers. PARTICIPANTS: Obese patients make up the
      majority of all patients seen in primary care (PC). The patients and physicians
      were recruited at the time of PC visits. MEASUREMENTS AND MAIN RESULTS: Percent
      patient-physician agreement and patient, provider and practice characteristics
      associated with agreement. Patients (456) and physicians (30) agreed about
      whether or not they discussed weight, physical activity (PA), and diet for 61% of
      office visits. There was disagreement on one of the items (weight, PA, or diet)
      for 23% of office visits, and for 2 or more of the items for 16% of the visits.
      Agreement was relatively greater for discussing weight than for discussing diet
      or physical activity. Physicians reported discussing weight issues more often
      than did patients. Overall patient-physician agreement was 0.51-0.59 (weighted
      Kappa statistic). In a multivariate analyses of factors associated with patient
      physician agreement, health insurance (odds ratio [OR]=3.67, p value = 0.002),
      physician description of patient weight status (OR = 2.27, p value = 0.002),
      patient report of how weight relates to health (OR = 1.70, p value = 0.04), and
      female patient gender (OR = 1.62, p = value = 0.02) were significantly related to
      agreement. CONCLUSIONS: Patients and providers disagreed about whether or not
      weight issues were discussed in a large number of primary care encounters in this
      study. Physicians may be able to improve care for their obese patients by
      focusing discussions on specific details of diet and physical activity behaviors,
      and by clarifying that patients perceive weight-related information has been
      shared.

PMID- 18322762
TI  - Performance of the Montreal Consensus in the diagnosis of gastroesophageal reflux
      disease in morbidly obese patients.
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) has been increasingly
      recognized in patients with morbid obesity. A recent global evidence-based
      consensus on GERD has been proposed, but its performance in patients with morbid
      obesity is unknown. The aim of this study was to assess the performance of the
      Montreal Consensus in the diagnosis of GERD in morbidly obese patients. METHODS:
      Seventy-five consecutive morbidly obese patients underwent GERD symptoms
      assessment, upper gastrointestinal endoscopy, and ambulatory esophageal pH
      monitoring "off PPI". The performance of the Montreal Consensus was determined by
      comparing two diagnostic algorithms: 1. a gold standard approach in which any
      GERD symptom and findings from both endoscopy and pH monitoring were taken into
      account, and 2. the approach with the Montreal Consensus, in which troublesome
      GERD symptoms and endoscopic findings were considered. RESULTS: GERD was found
      present in 57 patients by applying the gold standard approach. The Montreal
      Consensus identified 41 of these patients, whereas the remaining 34 patients were
      classified as "no GERD". Of these, 16 (47%) showed reflux esophagitis and/or
      abnormal pH-metry. The Montreal Consensus had an accuracy of 78.7%, sensitivity
      of 72% (95% CI 59-82%), specificity of 100% (95% CI 82-100%) and negative
      predictive value of 47% (95% CI 37-57%). CONCLUSIONS: In morbidly obese patients,
      the approach with the Montreal Consensus has high specificity and suboptimal
      sensitivity in the diagnosis of GERD. Its intermediate negative predictive value
      suggests that complementary investigation might be routine in these patients,
      particularly in those who do not present with troublesome GERD symptoms.

PMID- 18322763
TI  - The original experimental model in rats to study gastric banding surgery.
AB  - BACKGROUND: A new bariatric surgical experimental model in rats for aspects of
      investigation was created. METHODS: In 121 male Wistar rats with body mass 250
      270 g, the original gastric banding (GB) operation was performed. Sixty days
      after the surgical procedure, we measured body mass and upper part of the
      alimentary tract patency (radiography with contrast medium). RESULTS: One hundred
      twenty one rats were operated on. In the study group, the mortality was 0%. A
      complication (incisional hernia) was found in only three cases. The average
      weight of the rat in the GB group on the 60th day after the surgery was 355.0 +/-
      4.12 g, and that in the sham-operation group was 394.0 +/- 4.80 g (t test, t =
      6,073, p < 0.001). The daily weight gain in sham-operated rats was 2.23 +/- 0.07
      g, whereas in the GB group, it was 1.60 +/- 0.07 g (p < 0.02). Complete
      inhibition of weight gain was not observed. CONCLUSION: The rat model of GB
      surgery that we created is easy to perform, repeatable, long-lasting, relatively
      cheap, and can be used in various experimental trials of diverse aspects of
      surgery in the field of obesity.

PMID- 18322765
TI  - [Generics in Austria 2003-2008: an update].

PMID- 18322766
TI  - [Generic drugs: quality, efficacy, safety and interchangeability].
AB  - Since the introduction of generic drugs to the pharmaceutical market a sometimes
      emotional debate exists whether they are well-investigated and of high quality.
      There is some uncertainty about whether evidence of bioequivalence is enough to
      guarantee efficacy and safety of generic drugs. Some physicians ask the question
      if competent authorities are able to ascertain that the pharmaceutical quality of
      generics is acceptable. Doctors and patients sometimes are ill at ease about the
      interchangeability of innovator and generic products. This article describes how
      the European Union legislation ensures that a generic drug is only approved if
      its risk-benefit relationship is favourable and that it is essentially similar to
      the innovator product. In this context pharmacokinetic parameters are accepted as
      surrogates for clinical results because bioequivalence means therapeutic
      equivalence as well. For most drugs, current bioequivalence testing generally
      enables clinicians to routinely substitute generic for innovator products.
      Published findings, however, suggest that particular drugs may not be ideally
      suited for generic substitution when a patient is already on that drug. These are
      the so called critical dose medicinal products (drugs with a narrow therapeutic
      range). When starting a new therapy with any generic drug, however, its
      similarity to the innovator drug in terms of efficacy, safety and quality is
      guaranteed.

PMID- 18322767
TI  - [Simulation of laparoscopic surgery--four years' experience at the Department of
      Surgery of the University Hospital Marburg].
AB  - It is well known that learning curves are longer for laparoscopic surgery
      compared to open surgery. Recently, virtual reality (VR) simulation was developed
      as alternative to conventional training. Such a new training system makes it
      possible to offer a wide range of repeatable surgical situations, and thus,
      enable assessments based on direct observation of performance. During the last
      four years we did several studies using a VR simulator (LapSim). After a
      constructive validity study - discrimination between novices and experienced
      laparoscopic surgeons, we were able to show that advanced residents benefit most
      from a three-day practical course for laparoscopic surgery, while - in a further
      investigation - we found contrary to training at the Pelvitrainer that novices in
      laparoscopic surgery have the most benefit from VR training. Minimally invasive
      surgery is significantly more sophisticated for the surgeon than open surgery.
      While Research on laparoscopic surgery has focused primarily on the development
      and assessment of technical skills, non technical skills such as visual-spatial
      perception and stress coping has received much less attention. We showed that
      spatial perception as well as stress coping positively correlates with virtual
      laparoscopic skills. A high degree of spatial perception led to faster adaption
      to a non-stereo environment and correlated with high level of laparoscopic
      skills. Furthermore, Ineffective stress-coping strategies correlate with poor
      virtual laparoscopic performance. VR simulation seems to be a promising tool to
      improve laparoscopic skills in a modern apprenticeship model. According to
      patient safety, the development of this instrument for surgery should be advanced
      professionally just as a flight simulators in aviation.

PMID- 18322768
TI  - Myocardial disease in human immunodeficiency virus (HIV) infection: a review.
AB  - Heart muscle disease is the most important cardiovascular manifestation of HIV
      infection and is likely to become even more prevalent as HIV infected patients
      live longer. This may present as myocarditis, dilated cardiomyopathy or isolated
      left or right ventricular dysfunction. Myocardial involvement in HIV infection is
      multifactorial and may arise as a result of myocardial invasion with HIV itself,
      opportunistic infections, viral infections, autoimmune response to viral
      infection, drug-related cardiac toxicity, nutritional deficiencies, and prolonged
      immunosuppression. Both adults and children are affected with severity ranging
      from incidental microscopic inflammatory findings at autopsy to clinically
      significant cardiac disease with chronic cardiac dysfunction. It is associated
      with a poor prognosis, and results in symptomatic heart failure in up to 5% of
      HIV patients. Clinical pathological studies from the pre-HAART era show a 30%
      prevalence of cardiomyopathy in patients with AIDS. The introduction of highly
      active antiretroviral therapy (HAART) regimens has substantially modified the
      course of HIV disease by lengthening survival and improving quality of life of
      HIV-infected patients. There is also good evidence that HAART significantly
      reduces the incidence of cardiovascular manifestations of HIV infection. By
      preventing opportunistic infections and reducing the incidence of myocarditis,
      HAART regimens have reduced the prevalence of HIV-associated cardiomyopathy by
      almost 7-fold from the pre-HAART era. HAART is however only available to a
      minority of HIV infected individuals in most areas of the world and studies from
      the pre-HAART period still apply. In this review, the aetiopathogenesis and
      presentation of HIV related myocardial disease were reviewed and measures taken
      to improve survival discussed.

PMID- 18322769
TI  - Uteroplacental apoplexy (Couvelaire syndrome).

PMID- 18322770
TI  - [Partial reimbursement of prescription charges for generic drugs reduces costs
      for both health insurance and patients].
AB  - BACKGROUND: Rising costs of pharmaceuticals are a challenge to the public health
      care system. In collaboration with a company health insurance with 3143 members
      we analysed the economic benefit of reduced prescription fees for generic drugs
      in a 12-month period. METHODS: Within the observation period 1 euro per
      prescription of a generic drug was reimbursed to the insurants. On the basis of 5
      drug classes the prescribed proportion of generic drugs and the change in
      prescription pattern was computed. The acceptance of the intervention by the
      insurants was assessed using anonymous questionnaires. RESULTS: 42,219 drug
      prescriptons for insurants of the health insurance company were registered, with
      an overall cost of euro 843,954.95. In the observation period there was a 45%
      increase of the proportion of overall costs spent for generic drugs, from euro
      78,325.65 to euro 110,419.90, together with a 38% increase of prescriptions of
      generic drugs. The expenditures for reimbursements of prescription payments
      amounted to euro 9,984 (euro 1-74 to insurants). In the 5 selected drug classes
      the proportion of generic drugs increased from 23% before the observation period
      to 40%, whereby a cost reduction of euro 2.47 per prescription was achieved.
      Taking into account an overall increase of prescriptions of the selected drugs, a
      cost reduction from euro 188,811.45 to euro 173,677.15 was accomplished. This
      intervention was considered useful by 84% of all insurants. CONCLUSION: Financial
      incentives for insurants by partial reimbursement of prescription charges are
      effective for increasing the proportion of generic substitutes and for
      controlling drug costs.

PMID- 18322771
TI  - Human dirofilariosis in Hungary: an emerging zoonosis in central Europe.
AB  - INTRODUCTION: In the temperate regions of Europe, mainly Italy, France, Greece,
      and in recent years Hungary, a specific filarioid worm, Dirofilaria (Nochtiella)
      repens, a parasite of dogs, cats and some other carnivores, transmitted by
      mosquitoes, has occasionally been contracted, causing dirofilariosis in humans.
      We report a case of dirofilariosis and review all previously observed cases in
      Hungary. MATERIALS, METHODS AND RESULTS: The authors present a case of human
      subconjunctival dirofilariosis in a 56-year-old man with mild itching and a
      burning sensation in his right eye. A slow-moving, whitish, thread-like worm was
      detected by slit-lamp examination. The worm was surgically removed and
      parasitological examination identified it as an immature male Dirofilaria repens.
      A review of Hungarian cases from 1880 to 2000 is presented, with updates of
      earlier reports. In addition, 16 new cases (8 men; 8 women) diagnosed between
      2001 and 2006 are reviewed. The mean age of these 16 patients was 60 years; eight
      cases had ocular localization, seven were subcutaneous and one was diagnosed in a
      histopathological section of removed axillary lymph node in a patient with
      lymphoid leukemia. Twelve of the 16 identified Dirofilariae were females, four
      were males. According to their recorded histories the patients had not traveled
      internationally. CONCLUSION: Most of the above cases of dirofilariosis are
      certainly autochthonous infections. The increasing number of diagnosed cases
      suggests that this zoonosis is becoming more important in central Europe and that
      the incidence may increase with the improvement of clinical diagnosis.

PMID- 18322772
TI  - [RheumaCheck: development and evaluation of a German language screening
      instrument for rheumatic diseases].
AB  - OBJECTIVE: Early diagnosis of inflammatory rheumatic diseases is important for
      patients' prognosis and outcome. The mean time delay of 1 to 5 years in Germany
      between the initial symptoms and the first rheumatologist contact should be
      reduced. Efficiency of patient questionnaires for the identification of
      inflammatory rheumatic diseases has been demonstrated in other countries. The aim
      of our study was to develop a patient questionnaire in German identifying
      inflammatory rheumatic diseases with a high sensitivity and specificity as well
      as a high positive predictive value. PATIENTS AND METHODS: The RheumaCheck
      questionnaire was developed by adoption of the FDA-approved Connective Tissue
      Disease Screening Questionnaire. 1448 patients (195 controls, 437 patients
      suspicious for and 816 patients with known inflammatory rheumatic diseases)
      recruited by rheumatologists and general practitioners answered the questionnaire
      that additionally assessed comorbidities and sociodemographic data. A predictive
      algorithm was calculated. RESULTS: Mean age of the complete group (73.1% female)
      was 52.5 +/- 15.1 years. 53.1% had no comorbidity. Application of the algorithm
      yields a high sensitivity (77.6%) and specificity (79.9%). The area under the ROC
      curve was 0.85 (p < 0.0001). CONCLUSION: Being aware of a possible high rate of
      false true results RheumaCheck is a simple, efficient instrument easily filled
      out by patients. It can identify the group of patients that needs further
      investigation, care and assessment by a rheumatologist leading to earlier
      diagnosis and therapy. A web version of RheumaCheck is provided on www.rheuma
      check.de .

PMID- 18322773
TI  - Initial effects of low-level laser therapy on growth and differentiation of human
      osteoblast-like cells.
AB  - Low-level laser therapy is a clinically well established tool for enhancement of
      wound healing. In vitro studies have also shown that low level laser therapy has
      a biostimulatory effect on cells of different origin. The aim of this in vitro
      study was to investigate the initial effect of low-level laser therapy on growth
      and differentiation of human osteoblast-like cells. SaOS-2 cells were irradiated
      with laser doses of 1 J/cm2 and 2 J/cm2 using a diode laser with 670 nm wave
      length and an output power of 400 mW. Untreated cells were used as controls. At
      24 h, 48 h and 72 h post irradiation, cells were collected and assayed for
      viability of attached cells and alkaline phosphatase specific activity. In
      addition, mRNA expression levels of osteopontin and collagen type I were assessed
      using semi-quantitative RT-PCR. Over the observation period, cell viability,
      alkaline phosphatase activity and the expression of osteopontin and collagen type
      I mRNA were slightly enhanced in cells irradiated with 1 J/cm2 compared with
      untreated control cells. Increasing the laser dose to 2 J/cm2 reduced cell
      viability during the first 48 h and resulted in persistently lower alkaline
      phosphatase activity compared with the other two groups. The expression of
      osteopontin and collagen type I mRNA slightly decreased with time in untreated
      controls and cells irradiated with 1 J/cm2, but their expression was increased by
      treatment with 2 J/cm2 after 72 h. These results indicate that low-level laser
      therapy has a biostimulatory effect on human osteoblast-like cells during the
      first 72 h after irradiation. Further studies are needed to determine the
      potential of low-level laser therapy as new treatment concept in bone
      regeneration.

PMID- 18322774
TI  - [Mastitis with abscesses caused by esophageal fistula].
AB  - Mastitis originating from a fistula from intramediastinal esophago-jejunostomy
      following gastrectomy is an extremely rare event. We report on a 79-year old
      woman who had undergone repeated surgery due to recurrent breast abscesses for
      more than a year. The patient's history showed gastrectomy and esophago
      jejunostomy two years earlier, with subsequent undetected insufficiency of the
      anastomosis and inflammation of the breast. The reason for the recurrent breast
      abscesses was found intraoperatively to be due to a fistula which could be
      followed to the anastomosis. Histologically, vegetable tissue (food particles)
      was detected in the fistula specimen. Detailed assessment of the patient's
      history could have helped detecting the circumstances when the first breast
      abscess appeared. Exact preoperative diagnosis and accurate wound debridement
      could have revealed the real cause of the recurrent abscess formation much
      earlier.

PMID- 18322775
TI  - Bone marrow infection with bacillus Calmette-Guerin (BCG) after intravesical
      immunotherapy.
AB  - Instillation of bacillus Calmette-Guerin (BCG) into the urine bladder is an
      effective treatment of superficial bladder cancer. BCG-mediated anti-tumor
      activity appears to be a local phenomenon in which cell-mediated immunity,
      involving cytotoxic T cells, lymphokine-activated killer cells and natural killer
      cells, is important for the elimination of malignant cells. Serious side-effects
      of BCG therapy are rare; nevertheless, BCG is a live, attenuated strain of
      Mycobacterium (M.) bovis and may exhibit invasive properties. Both local and
      distant or generalized infections have been reported after treatment with BCG. We
      describe the case of a 68-year-old man who developed bone marrow infection with
      BCG two years after intravesical instillation of BCG for treatment of superficial
      bladder cancer. He presented with intermittent fever, weight loss and pronounced
      pancytopenia. A bone marrow biopsy specimen showed granulomatous inflammation and
      BCG was cultured from the urine. Anti-mycobacterial treatment with isoniazid,
      rifampicin and ethambutol (pyrazinamide is inactive against M. bovis) led to full
      clinical recovery of the patient.

PMID- 18322777
TI  - Molecular diagnosis of X-linked chronic granulomatous disease in Iran.
AB  - Chronic granulomatous disease (CGD) is an inherited disorder of pathogen killing
      by phagocytic leukocytes caused by mutations in NADPH oxidase subunits. Patients
      with CGD have life-threatening bacterial and fungal infections. Children's
      Medical Center at Tehran University is the referral center for immunodeficiency
      in Iran. During 2 years of study, 11 non-consanguineous families with clinically
      diagnosed CGD were referred to this center. In functional assays performed on
      neutrophils from affected children and their mothers; no activity or strongly
      decreased oxidase activity was detected in the patients' cells. In oxidase tests
      that scored this activity on a per-cell basis, a mosaic pattern was detected in
      the neutrophils from all 11 mothers. Western blot analysis revealed an X91
      degrees phenotype in all patients. Mutation screening in the CYBB gene encoding
      gp91(phox) by SSCP analysis followed by sequencing showed nine different
      mutations, including two novel mutations. The present survey is the first study
      aimed to analyze the clinical features and the molecular diagnosis of X-CGD in
      Iranian patients.

PMID- 18322778
TI  - Surgical treatment for chest wall invasion due to the local recurrence of breast
      cancer.
AB  - OBJECTIVE: In this study, we investigated the surgical results for chest wall
      invasion of local recurrence of breast cancer. PATIENTS AND METHODS: We reviewed
      eight patients who underwent a chest wall resection for local recurrence of
      breast cancer in our department between 1986 and 2004. RESULTS: All of the
      patients had local recurrence without any distant metastasis. All of them had
      skin ulcers with blood oozing. The operation procedures were Bt + Ax + Ic + Mj +
      Mn (Halsted mastectomy) in four patients, Bt + Ax + Ic + Mn (Patey procedure) in
      two patients, Bt + Ax + Ic (muscle-preserving mastectomy) in one patient, and Bt
      + Ax (Auchincloss procedure) in one patient. The intervals from the primary
      operation ranged from 14 months to 20 years. The maximum and minimum areas of the
      chest wall defect were 18 x 16 cm and 4.5 x 3.5 cm, respectively. Reconstruction
      of the chest wall was performed using a flap of the rectus abdominis muscle with
      polypropylene (Marlex) mesh in four patients, a flap of the rectus abdominis
      muscle combined with sandwich prosthesis of polypropylene mesh and
      methylmethacrylate in one patient, a flap of latissimus dorsi muscle in one
      patient, polypropylene mesh with pectoralis major muscle in one patient, and by
      direct closure in one patient. A survival of more than 3 years was achieved in
      seven patients and only one patient died 1 year and 2 months after the chest wall
      resection. CONCLUSION: In patients with the chest wall recurrence of breast
      cancer without distant metastasis, a surgical resection of the chest wall may be
      effective both for relieving pain and for control of the local hemorrhage. Seven
      out of the eight patients survived more than 3 years, suggesting that this
      surgical treatment could facilitate home health care and maintain a good quality
      of life for patients with breast cancer.

PMID- 18322779
TI  - Silk fibroin protein from mulberry and non-mulberry silkworms: cytotoxicity,
      biocompatibility and kinetics of L929 murine fibroblast adhesion.
AB  - Silks fibers and films fabricated from fibroin protein of domesticated mulberry
      silkworm cocoon have been traditionally utilized as sutures in surgery and
      recently as biomaterial films respectively. Here, we explore the possibility of
      application of silk fibroin protein from non-mulberry silkworm cocoon as a
      potential biomaterial aid. In terms of direct inflammatory potential, fibroin
      proteins from Antheraea mylitta and Bombyx mori are immunologically inert and
      invoke minimal immune response. Stimulation of murine peritoneal macrophages and
      RAW 264.7 murine macrophages by these fibroin proteins both in solution and in
      the form of films assayed in terms of nitric oxide and TNFalpha production showed
      comparable stimulation as in collagen. Kinetics of adhesion of L929 murine
      fibroblasts, for biocompatibility evaluation, monitored every 4 h from seeding
      and studied over a period of 24 h, reveal A. mylitta fibroin film to be a better
      substrate in terms of rapid and easier cellularization. Cell viability studies by
      MTT assay and flow cytometric analyses indicate the ability of fibroin matrices
      to support cell growth and proliferation comparable to collagen for long-term
      culture. This matrix may have potential to serve in those injuries where rapid
      cellularization is essential.

PMID- 18322780
TI  - Evaluation of physical-chemical properties and biocompatibility of a microrough
      and smooth bioactive glass particles.
AB  - The purpose of this study was to evaluate physical-chemical and biocompatibility
      characteristics of a simple synthesis and low cost experimental bioactive glass.
      Physical and chemical properties were analyzed using scanning electron microscopy
      (SEM), X-ray energy dispersive (EDX), X-ray fluorescence (XRF) and X-ray
      diffraction (XRD). The biomaterials were subcutaneously implanted into rats,
      according to the following groups: G1, PerioGlastrade mark; G2, Biograntrade
      mark, G3, Experimental Bioactive Glass U (BGU) and G4, Control (Sham). After 7,
      15, 21, 45, and 60 days, 5 animals/group/period were sacrificed and the
      subcutaneous tissue was dissected for histological and histometric analysis,
      considering inflammatory reaction and granulation area, presence of
      polymorphonuclear (PMN), monuclear (MN) and fibroblast (F) cells. SEM analysis of
      biomaterials showed irregular particles with different surface characteristics.
      EDX showed calcium, oxygen, sodium, phosphorus and silicon; XRF revealed silica
      oxide (SiO(2)), sodium oxide (Na(2)O), calcium oxide (CaO) and phosphorus oxide
      (P(2)O(5)). XRD indicated non crystalline phase. Measurement of tissue reaction
      showed similar results among the experimental groups at 45 and 60 days. No
      difference was found for PMN, MN and F cell counts. All biomaterials exhibited
      partial resorption. In conclusion, the experimental bioactive glass analyzed
      showed physical and chemical characteristics similar to the commercially
      available biomaterials, and was considered biocompatible, being partially
      reabsorbed in the subcutaneous tissue.

PMID- 18322781
TI  - Preparation and characterization of biphasic calcium phosphate ceramics of
      desired composition.
AB  - A modified processing route for fabricating dense and porous biphasic calcium
      phosphate (BCP) ceramics of desired and reproducible phase composition
      (hydroxyapatite (HA)/beta-tricalcium phosphate (beta-TCP) ratio) has been
      developed. The principal idea of the route was combining a precipitation and a
      solid phase methods. First, a nonstoichiometric (slightly carbonated calcium
      deficient) HA (CdHA) precipitate was synthesized by mixing a calcium carbonate
      (CaCO(3)) water suspension with an orthophosphoric acid (H(3)PO(4)) solution in
      abundance (related to the amount resulting in a stoichiometric HA) under definite
      conditions, and a powder of the precipitate was prepared and calcinated in air
      (860 degrees C, 1.5 h). In the second stage, a BCP ceramics of the composition
      determined by the calcium-deficiency in a calcinated powder (the acid abundance
      in a mixture) was processed by sintering powder compacts with or without a
      porosizer under appropriate conditions (1,200 degrees C, 2h). A calibrating
      dependence of the HA/beta-TCP ratio in the ceramics on the acid abundance has
      been plotted which enabled a controlled preparation of BCP ceramics. A
      correlation based on unresolved bands in nu(4)-PO (4) (3-) domain in IR-spectra
      of nanostructured BCP materials was found. Using the correlation, the process of
      CdHA --> beta-TCP transformation could be easily monitored. The density and
      microhardness of the BCP ceramics neglectly depended on the composition, however,
      the compressive strength did: the lower the HA/beta-TCP ratio, the higher the
      strength in the dense materials.

PMID- 18322782
TI  - Synthesis of gelatin-containing PHBV nanofiber mats for biomedical application.
AB  - Electrospinning is one of the fabrication method to form ultra-fine fiber in a
      nano-scale made of synthetic and natural extracellular matrix components for
      tissue-engineering applications. In this study, a nanofibrous scaffold was
      obtained by co-electrospinning poly (3-hydroxybutyrate-co-3-hydroxyvalerate)
      (PHBV) and gelatin in 2,2,2-trifluoroethanol (TFE) at a ratio of 50/50. The
      resulting fiber diameters were in the range of 400-1,000 nm without any beads.
      The nanofiber surfaces were characterized by attenuated total reflection-Fourier
      transform infrared spectroscopy (ATR-FTIR), electron spectroscopy for chemical
      analysis (ESCA), and atomic force microscopy. It was found, from cell culture
      experiments, that NIH 3T3 cells on the PHBV/gelatin nanofibrous scaffold more
      proliferated than on the PHBV nanofibrous scaffold.

PMID- 18322783
TI  - Photophysical characterization of new 3-amino and 3-acetamido BODIPY dyes with
      solvent sensitive properties.
AB  - The structural, electronic and photophysical properties of three new asymmetric,
      highly fluorescent difluoroborondipyrromethene (BODIPY) dyes, bearing an amino or
      an acetamido group at position 3 of the chromophoric core, have been studied in
      different apolar, polar and polar/protic solvents. The presence of the 3-amido
      group extents the delocalization of the pi-system, leading to bathochromic shifts
      in the absorption and fluorescence bands, as predicted by quantum mechanic
      calculations. The 3-amino dye shows photophysical properties highly dependent on
      the solvent polarity and acidity, and is characterized by a hypsochromic shift of
      its absorption band, with regard to the corresponding acetylated dye, as well as
      a low fluorescence quantum yield in acid media with proton concentration lower
      than 4 x 10(-4) M. In media with higher proton concentration, the BF(2) bridge
      group of the 3-amino dye is removed, yielding the corresponding non-fluorescent
      dipyrromethene precursor. These results suggest that the 3-amino dye could be
      used as a fluorescence probe for the study of the acidity of different
      environments.

PMID- 18322784
TI  - Anti-annexin II antibodies in systemic autoimmune diseases and antiphospholipid
      syndrome.
AB  - OBJECTIVES: The objective of this study were (1) to evaluate the prevalence of
      anti-annexin II antibodies in patients with various autoimmune diseases and
      antiphospholipid syndrome and (2) to correlate anti-annexin II antibodies with
      anti-phospholipid antibodies. MATERIALS AND METHODS: Anti-annexin II antibodies
      and anti-phospholipid were detected, using an enzyme-linked immunosorbent assay,
      in the serum of patients with primary antiphospholipid syndrome (n = 16),
      systemic lupus erythematosus (n = 53), primary Sjogren syndrome (n = 71),
      systemic sclerosis (n = 17), systemic vasculitis (n = 18), and rheumatoid
      arthritis (n = 119). Healthy blood donors (n = 99) were used as controls.
      RESULTS: Anti-annexin II antibodies were significantly more prevalent in patients
      with connective tissue diseases (8.5%), especially antiphospholipid syndrome
      (14.8%) and rheumatoid arthritis (10%), than in controls (2%). An inverse
      correlation was observed between anti-annexin II antibodies and antiphospholipid
      antibodies. CONCLUSION: Annexin II can be recognized by antibodies in serum from
      patients with systemic autoimmune disorders. Further studies are required to
      determine the clinical significance of anti-annexin II antibodies in rheumatoid
      arthritis and to determine their diagnostic value in discriminating clinical
      subgroups of patients with antiphospholipid syndrome.

PMID- 18322785
TI  - Autoimmune manifestations in common variable immunodeficiency.
AB  - INTRODUCTION: About 20% of subjects with common variable immune deficiency (CVID)
      develop an autoimmune complication, most often immune thrombocytopenia or
      hemolytic anemia. While the pathogenesis of autoreactivity is unknown for CVID
      subjects in general, and to a greater extent in those with autoimmunity, there is
      a loss of switched memory B cells. DISCUSSION: About 7-8% of CVID subjects have
      mutations in the transmembrane activator and calcium-modulating cyclophilin
      ligand interactor (TACI), a significant association with this immune defect,
      although the same mutations may be found in normal relatives and rarely in
      healthy blood donors. In addition to generalized B cell dysfunction, defective
      elimination of autoimmune B cells has been demonstrated.

PMID- 18322786
TI  - Autoimmunity in primary immunodeficiencies.

PMID- 18322787
TI  - Qualitative investigation of factors contributing to effective nutrition
      education for Navajo families.
AB  - OBJECTIVES: Obesity rates in American Indian and Alaskan Native children are a
      major health threat, yet effective ways to address this remain elusive. Building
      on an earlier dietary assessment of Navajo Head Start families which indicated a
      gap in parental nutrition awareness despite a strong program emphasis, the aim of
      this project was to identify culturally relevant nutrition education strategies
      for Navajo parents and educators of young children. METHODS: Eight focus group
      interviews were conducted with 41 parents and early childhood education
      paraprofessionals to identify contributors to both healthful and unhealthy food
      ways of Navajo preschoolers. RESULTS: were presented in two community venues to
      verify the themes and discuss implications. Results Barriers to healthful eating
      included availability/cost, parenting/control, preferences/habits, time
      pressures, and knowledge/education. Enablers to healthful eating included the
      categories of schools/education, and support/modeling. Reactions to these
      findings during community forums suggested (1) the need for stronger parenting
      and parental control over the food environment; (2) community-level action to
      address these barriers; and (3) the need for knowledge and culturally relevant
      educational strategies for caregivers and children. CONCLUSIONS: Implications for
      interventions include building upon existing community resources to enhance
      culturally relevant and respectful parental, family, and community support for
      affordable and acceptable food experiences and choices for young children and
      their families.

PMID- 18322788
TI  - Episodic activity in a heterogeneous excitatory network, from spiking neurons to
      mean field.
AB  - Many developing neural systems exhibit spontaneous activity (O'Donovan, Curr Opin
      Neurobiol 9:94-104, 1999; Feller, Neuron 22:653-656, 1999) characterized by
      episodes of discharge (active phases) when many cells are firing, separated by
      silent phases during which few cells fire. Various models exhibit features of
      episodic behavior by means of recurrent excitation for supporting an episode and
      slow activity-dependent depression for terminating one. The basic mechanism has
      been analyzed using mean-field, firing-rate models. Firing-rate models are
      typically formulated ad hoc, not derived from a spiking network description, and
      the effects of substantial heterogeneity amongst the units are not usually
      considered. Here we develop an excitatory network of spiking neurons (N-cell
      model) with slow synaptic depression to model episodic rhythmogenesis. This N
      cell model displays episodic behavior over a range of heterogeneity in bias
      currents. Important features of the episodic behavior include orderly recruitment
      of individual cells during silent phases and existence of a dynamical process
      whereby a small critical subpopulation of intermediate excitability conveys
      synaptic drive from active to silent cells. We also derive a general self
      consistency equation for synaptic drive that includes cell heterogeneity
      explicitly. We use this mean-field description to expose the dynamical
      bistability that underlies episodic behavior in the heterogeneous network. In a
      systematic numerical study we find that the robustness of the episodic behavior
      improves with increasing heterogeneity. Furthermore, the heterogeneity of
      depression variables (imparted by the heterogeneity in cellular firing
      thresholds) plays an important role in this improvement: it renders the network
      episodic behavior more robust to variations in excitability than if depression is
      uniformized. We also investigate the effects of noise vs. heterogeneity on the
      robustness of episodic behavior, especially important for the developing nervous
      system. We demonstrate that noise-induced episodes are very fragile, whereas
      heterogeneity-produced episodic rhythm is robust.

PMID- 18322789
TI  - Social disadvantage and the mental health of military personnel returning from
      Iraq and Afghanistan.

PMID- 18322790
TI  - Implementation matters: a review of research on the influence of implementation
      on program outcomes and the factors affecting implementation.
AB  - The first purpose of this review was to assess the impact of implementation on
      program outcomes, and the second purpose was to identify factors affecting the
      implementation process. Results from over quantitative 500 studies offered strong
      empirical support to the conclusion that the level of implementation affects the
      outcomes obtained in promotion and prevention programs. Findings from 81
      additional reports indicate there are at least 23 contextual factors that
      influence implementation. The implementation process is affected by variables
      related to communities, providers and innovations, and aspects of the prevention
      delivery system (i.e., organizational functioning) and the prevention support
      system (i.e., training and technical assistance). The collection of
      implementation data is an essential feature of program evaluations, and more
      information is needed on which and how various factors influence implementation
      in different community settings.

PMID- 18322791
TI  - The prevention delivery system: organizational context and use of comprehensive
      programming frameworks.
AB  - The purpose of this exploratory study is to investigate organizational-level
      mechanisms in the Prevention Delivery System (PDS) and their influence on
      implementing comprehensive programming frameworks (e.g., Communities that Care
      CtC) as the innovation. The PDS is part of the Interactive Systems Framework for
      Dissemination and Implementation (ISF) and describes key characteristics of
      innovation implementation and dissemination. The study addresses two research
      questions: (1) What types of organizational characteristics are related to
      successful use of each of the programming processes (i.e., planning,
      implementation, evaluation, and sustainability) that are part of comprehensive
      programming frameworks?; and (2) What are the similarities and differences in the
      organizational patterns correlated with use of each of the programming processes?
      Surveys, interview data, and other documents designed to assess organizational
      characteristics and extent of use of a comprehensive programming framework over
      time, were collected from 8 Community boards and 23 provider agencies. These
      organizations were responsible for planning and delivering substance abuse
      prevention services as part of a statewide initiative in Ohio. Data were analyzed
      using Spearman rho (and rank-biserial) correlations, with an emphasis on effect
      sizes. Results indicated that leadership, shared vision, process advocates, and
      technical assistance were common correlates of use across programming processes.
      However, the role played by these organizational variables differed for each
      programming process, pointing to complex interactions of the organizational
      infrastructure with other variables (i.e., characteristics of the innovation
      itself and external macro-level factors). This exploratory study provides
      preliminary data on the organizational-level mechanisms of the PDS and the
      complexity of their relationships with the other Systems in the Interactive
      Systems Framework.

PMID- 18322792
TI  - Dequalinium-induced cell death of yeast expressing alpha-synuclein-GFP fusion
      protein.
AB  - Intracellular toxic effects of the dequalinium-induced protofibrils of alpha
      synuclein have been investigated with the yeast system expressing alpha-synuclein
      GFP fusion protein in single copy, which appears in the green halo around the
      plasma membrane. Intracellular responses of the green fluorescent protein were
      analyzed as the cells were treated with dequalinium (DQ) and lactacystin. Yeast
      cells expressing alpha-synuclein-GFP were susceptible to both compounds in alpha
      synuclein-dependent manner. Upon DQ treatment, the green halo became smeared
      throughout the cytoplasm while lactacystin induced a few discrete green dots,
      reflecting intracellular formation of the protofibrils and the protein
      inclusions, respectively. The DQ-treated yeast cells were intensely stained with
      the nucleic acid stains of cell-permeable Hoechst 33342 and cell-impermeable
      propidium imidione, indicating that nucleus has been disrupted in addition to
      plasma membrane destabilization. Those DQ-treated yeast cells, however, still
      contained active mitochondria identified with MitoTracker Red. Therefore, the DQ
      induced protofibrillar state of alpha-synuclein-GFP has been suggested to cause
      the nuclear damage either independently or in combination with the membrane
      destabilization without affecting mitochondria.

PMID- 18322794
TI  - The cognitive enhancer SGS742 does not involve major known signaling cascades in
      OF1 mice.
AB  - In a previous study we have shown that SGS742, a cognitive enhancer acting by
      GABA(B) receptor antagonism improved spatial learning in OF1 mice. The aim of the
      study was therefore to screen representatives of several signaling cascades known
      to be involved in memory formation at the protein level. NaCl-, SGS742- treatment
      and yoked controls for NaCl and SGS742 were studied. Six hours following testing
      OF1 mice in the Morris water maze, hippocampal signaling proteins calmodulin
      kinase II (CaMKII) (phosphorylated (P) and non-phosphorylated (NP) form), CREB
      (P, NP), ERK (P, NP), BDNF, Egr-1, Trk-B and neuro-cytoskeleton elements drebrin
      and PSD-95 were determined by immunoblotting. Protein patterns were comparable
      between the control and SGS742 treated group revealing that these proteins may
      not be involved in the mechanisms underlying cognitive enhancement by SGS742 and
      this should be taken into account for interpretation and design of previous and
      future related neurochemical studies.

PMID- 18322796
TI  - Metastatic malignant fibrous histiocytoma to the duodenum.

PMID- 18322795
TI  - Underlying mechanism of quercetin-induced cell death in human glioma cells.
AB  - There has been considerable interest in recent years in the anti-tumor activities
      of flavonoids. Quercetin, a ubiquitous bioactive flavonoid, can inhibit
      proliferation and induce apoptosis in a variety of cancer cells. However, the
      precise molecular mechanism by which quercetin induces apoptosis in cancer cells
      is poorly understood. The present study was undertaken to examine the effect of
      quercetin on cell viability and to determine its underlying mechanism in human
      glioma cells. Quercetin resulted in loss of cell viability in a dose- and time
      dependent manner and the decrease in cell viability was mainly attributed to cell
      death. Quercetin did not increase reactive oxygen species (ROS) generation and
      the quercetin-induced cell death was also not affected by antioxidants,
      suggesting that ROS generation is not involved in loss of cell viability. Western
      blot analysis showed that quercetin treatment caused rapid reduction in
      phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. Transient
      transfection with constitutively active forms of MEK and Akt protected against
      the quercetin-induced loss of cell viability. Quercetin-induced depolarization of
      mitochondrial membrane potential. Caspase activity was stimulated by quercetin
      and caspase inhibitors prevented the quercetin-induced loss of cell viability.
      Quercetin resulted in a decrease in expression of survivin, antiapoptotic
      proteins. Taken together, these findings suggest that quercetin results in human
      glioma cell death through caspase-dependent mechanisms involving down-regulation
      of ERK, Akt, and survivin.

PMID- 18322797
TI  - Yield of 24-hour esophageal pH and bilitec monitoring in patients with persisting
      symptoms on PPI therapy.
AB  - Current management algorithms propose pH monitoring under proton pump inhibitors
      (PPIs) in suspected gastroesophageal reflux disease (GERD) with insufficient
      treatment response, but recent observations challenge this approach because of
      its low yield. AIM: To perform an audit of the outcomes of pH monitoring under
      PPI therapy in our unit, and to study the yield of additional nonacid reflux
      monitoring. METHODS: All pH monitoring studies under antireflux therapy since
      1997, with or without simultaneous Bilitec monitoring, were analyzed. RESULTS:
      From 1997 to 2003, 347 patients (157 men, mean age 49.4 +/- 0.8 years) underwent
      pH studies on PPI therapy (28% half-, 67% full-, and 5% double-dose PPI) for
      persisting typical (53%) or atypical (75%) symptoms. In 184 patients,
      simultaneous Bilitec monitoring was performed. Esophageal pH monitoring on PPI
      was pathological in 105 (30%) patients. Pathological pH monitoring on PPI was
      associated with typical reflux symptoms (64 versus 52%, P = 0.03), and a higher
      prevalence of persisting esophagitis (54 versus 36%, P < 0.005) and of hiatal
      hernia (58 versus 27%, P < 0.005). Bilitec monitoring on PPI therapy was
      pathological in 114 (62%) patients, of which 74 (40%) had normal pH monitoring.
      Adding Bilitec increased the rate of abnormal results over pH monitoring alone,
      from 38% to 69% on half-dose, from 27% to 69% on full-dose, and from 0% to 38% on
      double-dose PPI. CONCLUSIONS: The rate of abnormal pH monitoring in symptomatic
      GERD patients while on PPI therapy is relatively low, especially in those on
      double-dose PPI. Combined pH and Bilitec monitoring significantly increased the
      rate of ongoing pathological reflux compared to pH alone in refractory to PPI
      therapy GERD patients.

PMID- 18322798
TI  - Colon cancer knowledge and attitudes in an immigrant Haitian community.
AB  - OBJECTIVE: To qualitatively evaluate the views of Haitian immigrants on cancer
      and the influence of cultural and socio-ecological factors on cancer screening
      behavior. METHODS: Six focus groups, consisting of 4-10 individuals each, were
      conducted among Haitian adults at average risk for colorectal cancer. The
      interviews were conducted in Haitian Creole and featured questions that addressed
      beliefs and attitudes about general health, access to health care, colon cancer,
      and screening practices. RESULTS: The focus groups provided insight into the
      health service utilization patterns in the Haitian community, as well as the
      factors driving them including language and the pattern of accessing healthcare
      only for emergencies. CONCLUSIONS: Many misconceptions regarding cancer and its
      development were evident in the discussions. However participants were willing to
      follow the recommendations of a physician. This highlighted the importance in
      this community of disseminating information at every opportunity about
      preventative care, including colorectal cancer screening.

PMID- 18322799
TI  - B1 integrin/Fak/Src signaling in intestinal epithelial crypt cell survival:
      integration of complex regulatory mechanisms.
AB  - The molecular determinants which dictate survival and apoptosis/anoikis in human
      intestinal crypt cells remain to be fully understood. To this effect, the roles
      of beta1 integrin/Fak/Src signaling to the PI3-K/Akt-1, MEK/Erk, and p38
      pathways, were investigated. The regulation of six Bcl-2 homologs (Bcl-2, Mcl-1,
      Bcl-X(L), Bax, Bak, Bad) was likewise analyzed. We report that: (1) Anoikis
      causes a down-activation of Fak, Src, Akt-1 and Erk1/2, a loss of Fak-Src
      association, and a sustained/enhanced activation of p38beta, which is required as
      apoptosis/anoikis driver; (2) PI3-K/Akt-1 up-regulates the expression of Bcl-X(L)
      and Mcl-1, down-regulates Bax and Bak, drives Bad phosphorylation (both
      serine112/136 residues) and antagonizes p38beta activation; (3) MEK/Erk up
      regulates Bcl-2, drives Bad phosphorylation (serine112 residue), but does not
      antagonize p38bactivation; (4) PI3-K/Akt-1 is required for survival, whereas
      MEK/Erk is not; (5) Src acts as a cornerstone in the engagement of both pathways
      by beta1 integrins/Fak, and is crucial for survival; and (6) beta1 integrins/Fak
      and/or Src regulate Bcl-2 homologs as both PI3-K/Atk-1 and MEK/Erk combined.
      Hence, beta1 integrin/Fak/Src signaling translates into integrated mediating
      functions of p38beta activation and regulation of Bcl-2 homologs by PI3-K/Akt-1
      and MEK/Erk, consequently determining their requirement (or not) for survival.

PMID- 18322800
TI  - Secondary necrosis in multicellular animals: an outcome of apoptosis with
      pathogenic implications.
AB  - In metazoans apoptosis is a major physiological process of cell elimination
      during development and in tissue homeostasis and can be involved in pathological
      situations. In vitro, apoptosis proceeds through an execution phase during which
      cell dismantling is initiated, with or without fragmentation into apoptotic
      bodies, but with maintenance of a near-to-intact cytoplasmic membrane, followed
      by a transition to a necrotic cell elimination traditionally called "secondary
      necrosis". Secondary necrosis involves activation of self-hydrolytic enzymes, and
      swelling of the cell or of the apoptotic bodies, generalized and irreparable
      damage to the cytoplasmic membrane, and culminates with cell disruption. In vivo,
      under normal conditions, the elimination of apoptosing cells or apoptotic bodies
      is by removal through engulfment by scavengers prompted by the exposure of
      engulfment signals during the execution phase of apoptosis; if this removal fails
      progression to secondary necrosis ensues as in the in vitro situation. In vivo
      secondary necrosis occurs when massive apoptosis overwhelms the available
      scavenging capacity, or when the scavenger mechanism is directly impaired, and
      may result in leakage of the cell contents with induction of tissue injury and
      inflammatory and autoimmune responses. Several disorders where secondary necrosis
      has been implicated as a pathogenic mechanism will be reviewed.

PMID- 18322801
TI  - Neuropsychological characteristics of dementia with Lewy bodies and Parkinson's
      disease with dementia: differentiation, early detection, and implications for
      "mild cognitive impairment" and biomarkers.
AB  - Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) are
      neurodegenerative conditions sharing a disorder of alpha-synuclein metabolism.
      Temporal differences in the emergence of symptoms and clinical features warrant
      the continued clinical distinction between DLB and PDD. While DLB and PDD groups'
      neuropsychological profiles often differ from those in Alzheimer's disease (AD),
      the diagnostic sensitivity, specificity, and predictive values of these profiles
      remain largely unknown. PDD and DLB neuropsychological profiles share sufficient
      similarity to resist accurate and reliable differentiation. Although
      heterogeneous cognitive changes (predominantly in memory and executive function)
      may manifest earlier and more frequently than previously appreciated in
      Parkinson's disease (PD), and executive deficits may be harbingers of dementia,
      the enthusiasm to uncritically extend the concept of mild cognitive impairment
      (MCI) to PD should be tempered. Instead, future research might strive to identify
      the precise neuropsychological characteristics of the prodromal stages of PD,
      PDD, and DLB which, in conjunction with other potential biomarkers, facilitate
      early and accurate diagnosis, and the definition of neuroprotective,
      neurorestorative, and symptomatic treatment endpoints.

PMID- 18322802
TI  - Cushing's syndrome due to ectopic ACTH production by (neuroendocrine) prostate
      carcinoma.
AB  - Ectopic adrenocorticotropin (ACTH) secretion accounts for less than 10% of all
      causes of endogenous Cushing's syndrome (CS) and is usually associated with
      neuroendocrine tumors and small cell carcinoma of the lung. We report the case of
      a 62-year-old man with CS due to ectopic ACTH production by small cell carcinoma
      of the prostate. He presented with severe hypercortisolism and associated
      symptoms. Plasma neuron specific enolase (NSE) was grossly elevated. Despite
      performing a laparoscopic bilateral adrenalectomy, the patient died as a result
      of sepsis with multi-organ failure. Post-mortem immunohistochemical staining of
      prostate tumor tissue showed ACTH expression. ACTH staining was also performed in
      four additional patients with small cell carcinoma of the urinary tract without
      CS. None of these additional cases showed a positive staining for ACTH. Although
      a rare cause of ectopic ACTH production, neuroendocrine prostate carcinoma should
      be considered in male patients with Cushing's syndrome, in particular in those
      with an occult source of ACTH overproduction.

PMID- 18322803
TI  - The promise and perils of CNS drug delivery: a video debate.
AB  - Neurodegenerative and infectious disorders related to host genetics, aging, and
      environment are rapidly increasing. Drugs, vaccines, or regenerative proteins
      offer "real" possibilities for positively affecting disease outcomes but are
      limited by access across the blood-brain barrier. New developments in
      nanomedicine and cell based drug delivery are becoming available. These
      discoveries can lead to improved neurological disease outcomes. Such obstacles
      include the toxicities inherent in the delivery systems de novo such as immuno-
      and neurological dysfunctions and perturbations of blood-brain barrier function.
      This debate by leading experts in the field highlights the promise and perils of
      CNS drug delivery. Click on Supplemental HTML to watch the streaming video.

PMID- 18322804
TI  - Plant Sar1 isoforms with near-identical protein sequences exhibit different
      localisations and effects on secretion.
AB  - In plants, differentiation of subdomains of the endoplasmic reticulum (ER)
      dedicated to protein export, the ER export sites (ERES), is influenced by the
      type of export-competent membrane cargo to be delivered to the Golgi. This raises
      a fundamental biological question: is the formation of transport intermediates at
      the ER for trafficking to the Golgi always regulated in the same manner? To test
      this, we followed the distribution and activity of two plant Sar1 isoforms. Sar1
      is the small GTPase that regulates assembly of COPII (coat protein complex II) on
      carriers that transport secretory cargo from ER to Golgi. We show that, in
      contrast to a tobacco Sar1 isoform, the two Arabidopsis Sar1 GTPases were
      localised at ERES, independently of co-expression of Golgi-destined membrane
      cargo in tobacco cells. Although both isoforms labelled ERES, one was found to
      partition with the membrane fraction to a greater extent. The different
      distribution of fluorescent fusions of the two isoforms was influenced by the
      nature of an amino acid residue at the C-terminus of the protein, suggesting that
      the requirements for membrane association of the two GTPases are not equal.
      Furthermore, functional analyses based on the secretion of the bulk flow marker
      alpha-amylase indicated that over-expression of GTP-restricted mutants of the two
      isoforms caused different levels of ER export inhibition. These novel results
      indicate a functional heterogeneity among plant Sar1 isoforms.

PMID- 18322805
TI  - Genetic diversity in maize landraces from indigenous settlements of Northeastern
      Argentina.
AB  - In South America, native maize germplasm has been extensively studied
      particularly for the Andean region. However, relatively few genetic diversity
      studies include materials from the eastern region of the continent. Herein we
      present a genetic diversity characterization of four Popcorn maize landraces,
      maintained in indigenous settlements, from Northeastern Argentina (NEA). In
      addition, one Popcorn landrace from Northwestern Argentina (NWA) was incorporated
      for comparison. We characterized these landraces using ten microsatellite
      markers. For the whole data set, a total of 65 alleles were found, with an
      average of 7.22 alleles per locus. The average gene diversity was 0.370. Global
      fit to Hardy-Weinberg proportions was observed in all landraces. Global estimates
      of F (ST) revealed a significant differentiation among the populations.
      Individual Neighbor-joining clustering and Bayesian analyses allowed the
      recognition of most populations studied. Two main groups were distinguished by
      the Neighbor-joining clustering of populations. This grouping pattern would be
      consistent with a hypothesis of successive introductions of Popcorn in South
      America. The results presented will be useful to design strategies that maximize
      the utility of maize genetic resources.

PMID- 18322806
TI  - Electrocardiographic criteria of left ventricular hypertrophy in general
      population.
AB  - The question on whether the electrocardiographic criteria are reliable for
      detection of left ventricular hypertrophy (LVH) and play a role in predicting
      outcome is open. Answer can only proceed from population-based studies over
      unselected people followed up for years. In this study, 1,699 subjects from
      general population underwent echocardiogram and standard electrocardiogram (ECG)
      codified for LVH with Minnesota code and with other five methods. Other items
      were also recorded and used as covariables. Left ventricular mass index (LVMI)
      was 127.6 +/- 44.9 g m(-2) in men and 120.8 +/- 41.2 g m(-2 )in women, and
      correlated directly with age in both genders. Prevalence of echocardiographic LVH
      was 36.6% in men and 53.4% in women. LVMI correlated directly with the Sokolow
      Lyon score in both genders at any age, with the Romhilt-Estes, Cornell and R(aVL)
      scores in all subjects but elderly men, and with the Lewis score in men and women
      aged < or =69 years. Sensitivity and the predictive value of electrocardiographic
      tests, as well as the prevalence of LVH diagnosed with electrocardiographic
      criteria, were always low. Specificity was high for all the tests, and in
      particular for the Cornell index. Only when diagnosed with echocardiogram or with
      the Sokolow-Lyon criterion, LVH was an independent predictor of mortality. We
      conclude that electrocardiographic tests cannot be used as a surrogate of
      echocardiogram in detecting LVH in the general population because their positive
      predictive value (PPV) is unacceptably low. On the contrary, they could replace
      echocardiography in the follow up and for prediction of outcome, when LVH has
      previously been correctly diagnosed with other methods.

PMID- 18322807
TI  - Working conditions and weight gain: a 28-year follow-up study of industrial
      employees.
AB  - Longitudinal studies observing working conditions and weight gain are rare. We
      aimed to study whether weight gain can be predicted by working conditions or
      changes in them in a 28-year follow-up. The study population consisted of working
      aged industrial employees (n = 449). Data on height and weight were collected in
      clinical examinations in 1973, 1983 and 2001, and information on working
      conditions by questionnaires. We analysed the impact of changes in physical
      strain, temporal requirements and indicators of mental strain at work in 1973 and
      1983 on weight changes using analysis of variance, logistic regression analysis
      and linear mixed longitudinal growth model. The latter was done to account for
      individual variation in temporal weight change over the study period. Weight gain
      was prominent in the data and about a third of the participants gained at least
      15 kg by the final survey. Changes in physical strain and temporal requirements
      including working overtime hours among men, and experiencing increased working
      pace among women, were associated with greater mean weight gain and major weight
      gain. Job efforts and increasing mental strain showed weak associations with
      weight gain in men. Changes in the physical strain and temporal requirements seem
      to predict weight gain but working conditions were in general mostly weakly
      associated with weight gain in this cohort of initially young adults. The results
      highlight the importance of stable working hours and reasonable workload on
      healthy weight.

PMID- 18322808
TI  - Cancer in the Sami population of Sweden in relation to lifestyle and genetic
      factors.
AB  - The reindeer herding Sami of Sweden have low incidences of cancer. The aim of the
      present study was to investigate the cancer risk in a large cohort of Swedish
      Sami, containing Sami with different lifestyle and genetic Sami heritage. A
      cohort of 41,721 Sami identified in official national registers between 1960 and
      1997, was divided into two sub-populations -- reindeer herding Sami (RS) and non
      reindeer herding Sami (NRS). A demographically matched non-Sami reference
      population (NS) was used as standard when incidence and mortality ratios were
      calculated. Incidence and mortality data were obtained from the Swedish Cancer
      and Cause of Death Registers for the period 1961-2003. For Sami men, lower risks
      were found for cancers of the colon and prostate, and for malignant melanoma and
      non-Hodkins lymphoma, but higher for stomach cancer. The Sami women showed higher
      risks for cancers of the stomach and the ovaries, but lower risk for cancer of
      the bladder. The RS demonstrated lower relative cancer risks compared with the
      NRS. The lowest relative risk was found among the RS men, while the highest were
      observed among the NRS women. The RS men who had adopted a more westernized
      lifestyle showed a similar relative risk for prostate cancer as that of the NS
      living in the same region. Most of these differences in cancer risks could
      probably be ascribed to differences in lifestyle. It is concluded that the
      traditional Sami lifestyle contains elements, e.g. dietary contents and physical
      activity that may protect them from developing cancer.

PMID- 18322809
TI  - Geographical differences in mortality of severely injured patients in Italy.
AB  - BACKGROUND: In Italy there are no accepted standards for trauma care nor
      dedicated programs for quality assessment on a national scale, like trauma
      registries. At the same time there seems to be a north-south gradient in the
      quality of health care. We hypothesized that geographical inequalities of health
      care quality may affect trauma mortality. METHODS: Retrospective comparison of
      hospital mortality by Cox regression in three main areas of Italy adjusted for
      age, Glasgow Coma Scale and source of admission. A leading national database on
      patients admitted to intensive care units (ICU) in the years 2002-2005 was used.
      9162 adult trauma cases admitted to the ICU from the emergency department were
      included. RESULTS: There is a significant north-south gradient of risk. Compared
      to the north, the risk of death is about 60% higher in the south and about 30%
      higher in the central region. These figures are similar in both referral centres
      and other hospitals and both in the head-injured only and total injured cases.
      CONCLUSION: Despite the limitations of this study, mainly related to sampling
      issues, risk-adjustment and incomplete follow-up, the large geographic
      differences in mortality that we found highlight likely deficiencies in the
      quality of trauma care that deserve further accurate assessment.

PMID- 18322810
TI  - Environmentally relevant cadmium concentrations affect development and induce
      apoptosis of Paracentrotus lividus larvae cultured in vitro.
AB  - Sea urchin embryos and larvae represent suitable model systems on where to
      investigate the effects of heavy metals on development and cell viability. Here,
      we tested the toxic effects of low (10(-12 )M), medium (10(-9 )M), and high (10(
      6 )M) cadmium chloride concentrations, mimicking unpolluted, moderately and
      highly polluted seawaters, respectively, on Paracentrotus lividus sea urchins
      offspring. Larvae were continuously treated from fertilization and inspected at
      time intervals comprised between 10 and 30 days of development. Delays and/or
      morphological abnormalities were firstly evident in larvae treated for 15 days
      with high cadmium (10(-6 )M) and for 25 days with medium cadmium (10(-9 )M).
      Major defects consisted in the reduction and lack of arms and skeleton
      elongation. No obvious differences with respect to controls were observed in
      embryos/larvae exposed to low cadmium (10(-12) M), even after 30 days of
      exposure. Using in situ terminal deoxynucleotidyl transferase-mediated dUTP nick
      end labeling assay (TUNEL) assay on larvae whole mounts, we detected apoptosis
      after 10 days of treatment with 10(-6) and 10(-9) M CdCl(2,) when no
      morphological abnormalities were recognizable yet. Supernumerary apoptotic cells
      were found in arm buds, ciliary bands, and apex. In conclusion, echinoderm
      embryos and larvae represent candidates of choice for the study of stress and
      defense mechanisms activated by cadmium exposure.

PMID- 18322811
TI  - A prospective study of waist circumference and body mass index in relation to
      colorectal cancer incidence.
AB  - OBJECTIVES: To study the association between waist circumference and colorectal
      cancer, and whether it is independent of body mass index (BMI). METHODS: Between
      1997 and 2005, 953 incident colorectal cancer cases (546 men and 407 women) were
      identified among 95,151 participants (44,068 men and 51,083 women) from the
      Cancer Prevention Study-II Nutrition Cohort. RESULTS: Waist circumference was
      associated with increased colorectal cancer incidence in both men (multivariable
      adjusted rate ratio (RR) 1.68, 95% confidence interval (CI) 1.12-2.53 for waist
      circumference > or =120 cm compared to <95 cm, p trend = 0.006) and women (RR
      1.75, 95% CI 1.20-2.54 for > or =110 compared to <85 cm, p trend = 0.003). High
      levels of BMI were also associated with increased risk. After adjustment for BMI,
      waist circumference remained associated with a nonstatistically significant
      increase in colorectal cancer incidence in both men (RR 1.41, 95% CI 0.81-2.45
      for > or =120 compared to <95 cm, p trend = 0.10) and women (RR 1.48, 95% CI 0.89
      2.48 for > or =110 compared to <85 cm, p trend = 0.13). CONCLUSIONS: Our results
      confirm that waist circumference is associated with increased colorectal cancer
      incidence, possibly partially independent of BMI.

PMID- 18322812
TI  - Gynecological cancer survivors' health behaviors and their associations with
      quality of life.
AB  - OBJECTIVES: To evaluate health behaviors (smoking, physical activity, fruit and
      vegetable intake) and body mass index of gynecological cancer survivors and their
      association with quality of life. METHODS: We collected cross-sectional mail
      survey data from 802 gynecological cancer survivors (56% response rate) The
      questionnaire included validated measures of health behaviors, quality of life,
      clinical status, and demographics. RESULTS: Depending on gynecological cancer
      subtype, 61-68% were insufficiently active or sedentary, 19-44% were obese, 31
      41% had less than two daily serves of fruit, 82-89% had less than five serves of
      vegetables and 6-21% smoked. Significantly more endometrial than other cancer
      survivors were obese (44%; 95% CI 41-47%); smoking was more prevalent among
      cervical cancer survivors (21%; 95% CI 19-23%). Using general linear modeling we
      identified a positive linear trend of physical activity level with quality of
      life (p = 0.039). Being insufficiently active or sedentary was also associated
      with not meeting the guidelines for fruit and vegetable consumption, with smoking
      and with overweight/obesity. CONCLUSIONS: This research demonstrates the
      importance of integrating physical activity into follow-up of gynecological
      cancer survivors. Interventions to improve physical activity and test the causal
      effect of exercise on quality of life are a future research priority.

PMID- 18322813
TI  - Statin use and prostate cancer risk in a large population-based setting.
AB  - BACKGROUND: Statins are a commonly used cholesterol-lowering drug, which also
      have the potential to affect cancer risk and progression. Results from previous
      studies offer mixed conclusions. METHODS: To evaluate the relation between statin
      use and prostate cancer risk, we conducted a retrospective cohort study during 1
      January 1990 to 31 August 2005 among men 45-79 years receiving care within Group
      Health, an integrated healthcare delivery system. Information on statin use and
      covariates were obtained from health plan databases. We identified incident
      prostate cancer cases through the Surveillance, Epidemiology, and End Results
      cancer registry. We used Cox proportional hazards models to estimate the hazard
      ratios (HR) and 95% confidence intervals (CI) for prostate cancer among statin
      users compared to non-users. RESULTS: Among 83,372 men studied, median follow-up
      time was 5.7 years and 2,532 prostate cancer cases were identified. About 14.4%
      used statins over the study period and median duration of use was 3.3 years.
      Compared to non-users, hydrophobic statin users had a reduced risk of prostate
      cancer (HR = 0.79; 95% CI, 0.66-0.94), and results are suggestive of a reduced
      risk among ever users of statins (HR = 0.88; 95% CI, 0.76-1.02) and hydrophilic
      statin users (HR = 0.67; 95% CI, 0.33-1.34). There was no trend in risk by
      duration of statin use, and no association between statin use and cancer
      aggressiveness, stage, or grade. CONCLUSION: Overall, this study does not support
      an associated between statin use and prostate cancer but a reduced risk cannot be
      ruled out.

PMID- 18322814
TI  - Folate and MTHFR: risk of adenoma recurrence in the Polyp Prevention Trial.
AB  - BACKGROUND: Low dietary folate intake has been associated with colorectal cancer
      risk and adenoma recurrence. A C/T transition at position 677 in the gene
      encoding methlylenetetrahydrofolate reductase (MTHFR C677T) has been reported to
      interact with folate intake to modulate colorectal adenoma recurrence or cancer
      risk. METHODS: We investigated the association between MTHFR, total folate, and
      the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. We
      compared 625 individuals with any adenoma recurrence after 4 years (266
      individuals with multiple (> or =2) recurrent adenomas and 101 individuals with
      advanced adenoma recurrence) to 978 individuals with no adenoma recurrence. Odds
      ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were
      calculated using unconditional logistic regression. We also investigated effect
      modification of the MTHFR genotype associations by total folate intake. RESULTS:
      In general, no statistically significant associations were found between quartile
      of folate intake (dietary or total) and adenoma recurrence. The MTHFR CT genotype
      was associated with a significantly increased risk of multiple adenoma recurrence
      (OR: 1.34, 95% CI: 1.00, 1.81). No significant interaction was noted for total
      folate and MTHFR genotype, though an increased risk of recurrence noted for the
      MTHFR CT genotype was statistically significant only for those individuals with
      below median intake of total folate. CONCLUSION: We report that the MTHFR 677 CT
      genotype was associated with increased risk of adenoma recurrence (specifically
      multiple adenoma recurrence) 4 years after polypectomy.

PMID- 18322815
TI  - Correction for under-ascertainment in cancer cases in the very elderly (aged
      75+): external reference method.
AB  - OBJECTIVE: Any fall-off in the age-specific cancer incidence curve in oldest age
      groups may be suggestive of under-ascertainment. This article introduces a
      correction method for under-ascertainment of cancer cases in the very elderly
      (aged 75+). METHODS: Corrected age-specific rates for a certain cancer are
      calculated by summing the age-specific rates of that cancer for two lower age
      groups multiplied by a corresponding coefficient from an external reference
      cancer registry (sex-, site-, and age-specific coefficients from the Finnish
      Cancer Registry, a nation-wide population-based registry with high data
      validity). In order to examine this new method, Lithuanian Cancer Registry data
      for the period 1993-97 was chosen as an example. RESULTS: Age-specific incidence
      curves of cancers in both sexes and most of cancer sites in Lithuania
      demonstrated the presence of under-ascertainment in the oldest age groups (over
      75). Comparison of the corrected incidence rates for 1995 with the original ones
      showed that without correction for under-ascertainment, crude rates (and
      consequently number of new cases) were underestimated by around 10%.
      Underestimation for the year 2050 in Lithuania was approximately 20%. Depending
      on cancer site and sex, the percentage of underestimation varied substantially.
      CONCLUSION: In many cancer registries, after correction for under-ascertainment
      in elderly age groups, the estimates of number of new cases and incidence rates
      increase. With respect to prepare future projections of incidence, when the
      effects of an aging population need to be taken into account, accurate age
      specific rates in the upper age groups are important. Without correction, cancer
      occurrence measures may be substantially underestimated, which may lead to
      inadequate resource allocations for cancer control.

PMID- 18322816
TI  - Gender- and race-specific comparison of tobacco-associated cancer incidence
      trends in Florida with SEER regional cancer incidence data.
AB  - OBJECTIVE: Analysis of state and national tobacco-associated cancer trends is
      critical for the identification of high-risk regions of the country that require
      the attention of the public health community. This study compares Florida race-
      and gender-specific cancer trends with pooled data obtained from nine
      Surveillance, Epidemiology, and End Results (SEER-9) registries. METHODS: Age
      adjusted, race- and gender-specific cancer incidence trends were evaluated using
      joinpoint regression analysis. Pooled, age-adjusted incidence rates and
      standardized incidence rate ratios were computed for each cancer for the years
      1999-2003 to compare Florida to SEER-9. RESULTS: Relative to SEER-9 whites and
      irrespective of gender, lung cancer rates in white Floridians were elevated
      through the 1990s. However, lung cancer rates have recently declined at a steeper
      rate among white Floridians than among SEER-9 whites. For years 1999-2003, black
      Floridians had significantly lower rates of lung, bladder, pancreas, and kidney
      cancer relative to SEER-9 blacks. The opposite pattern was evident for white
      Floridians with significantly higher rates of lung and laryngeal cancer relative
      to SEER-9 whites. CONCLUSION: Progress in the reduction of tobacco-associated
      cancers among white Floridians lags behind the progress noted in SEER-9
      registries suggesting that additional state-directed smoking prevention and
      smoking cessation measures are needed.

PMID- 18322817
TI  - Prey mediated effects of Bt maize on fitness and digestive physiology of the red
      spider mite predator Stethorus punctillum Weise (Coleoptera: Coccinellidae).
AB  - The present study investigated prey-mediated effects of two maize varieties
      expressing a truncated Cry1Ab, Compa CB (event Bt176) and DKC7565 (event MON810),
      on the biology of the ladybird Stethorus punctillum. Although immuno-assays
      demonstrated the presence of Cry1Ab in both prey and predator collected from
      commercial maize-growing fields, neither transgenic variety had any negative
      effects on survival of the predator, nor on the developmental time through to
      adulthood. Furthermore, no subsequent effects on ladybird fecundity were
      observed. As a prerequisite to studying the interaction of ladybird proteases
      with Cry1Ab, proteases were characterised using a range of natural and synthetic
      substrates with diagnostic inhibitors. These results demonstrated that this
      predator utilises both serine and cysteine proteases for digestion. In vitro
      studies demonstrated that T. urticae were not able to process or hydrolyze
      Cry1Ab, suggesting that the toxin passes through the prey to the third trophic
      level undegraded, thus presumably retaining its insecticidal properties. In
      contrast, S. punctillum was able to activate the 130 kDa protoxin into the 65 kDa
      fragment; a fragment of similar size was also obtained with bovine trypsin, which
      is known to cleave the protoxin to the active form. Thus, despite a potential
      hazard to the ladybird of Bt-expressing maize (since the predator was both
      exposed to, and able to proteolytically cleave the toxin, at least in vitro), no
      deleterious effects were observed.

PMID- 18322818
TI  - A modified n-3 fatty acid desaturase gene from Caenorhabditis briggsae produced
      high proportion of DHA and DPA in transgenic mice.
AB  - The functions of polyunsaturated fatty acids (PUFAs) have been widely
      investigated. In mammals, levels of n-3 PUFAs are relatively low compared to
      those of n-6 PUFAs. Either a lack of n-3 PUFAs or an excess of n-6 PUFAs could
      potentially cause health problems in humans. Hence, methods to increase the
      amount of n-3 PUFAs in diet have been intensely sought. In this study, we
      demonstrated that the n-3 fatty acid desaturase gene (sFat-1) synthesized from
      revised and optimized codons based on roundworm Caenorhabditis briggsae genomic
      gene for enhanced expression in mammals was successfully expressed in Chinese
      hamster ovary (CHO) cells and significantly elevated cellular n-3 PUFA contents.
      We generated sFat-1 transgenic mice by introducing mammal expression vector DNAs
      containing the sFat-1 gene into regular mice through the method of
      microinjection. Fatty acid compositions were then altered and the levels of
      docosahexaenoic acid (DHA, 22:6n-3) and docosapentaenoic acid (DPA, 22:5n-3) were
      greatly increased in these transgenic mice. Various types of tissues in the
      transgenic mice produced many types of n-3 PUFAs, such as alpha-linolenic acid
      (ALA; 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3), DPA, and DHA, for example,
      muscle tissues of the transgenic mice contained 12.2% DHA, 2.0% DPA, and 23.1%
      total n-3 PUFAs. These research results demonstrated that the synthesized sFat-1
      gene with modified and optimized codons from C. briggsae possess functional
      activity and greater capability of producing n-3 PUFAs, especially DHA and DPA,
      in transgenic mice.

PMID- 18322819
TI  - Genus-wide Bacillus species identification through proper artificial neural
      network experiments on fatty acid profiles.
AB  - Gas chromatographic fatty acid methyl ester analysis of bacteria is an easy,
      cheap and fast-automated identification tool routinely used in microbiological
      research. This paper reports on the application of artificial neural networks for
      genus-wide FAME-based identification of Bacillus species. Using 1,071 FAME
      profiles covering a genus-wide spectrum of 477 strains and 82 species, different
      balanced and imbalanced data sets have been created according to different
      validation methods and model parameters. Following training and validation, each
      classifier was evaluated on its ability to identify the profiles of a test set.
      Comparison of the classifiers showed a good identification rate favoring the
      imbalanced data sets. The presence of the Bacillus cereus and Bacillus subtilis
      groups made clear that it is of great importance to take into account the
      limitations of FAME analysis resolution for the construction of identification
      models. Indeed, as members of such a group cannot easily be distinguished from
      one another based upon FAME data alone, identification models built upon this
      data can neither be successful at keeping them apart. Comparison of the different
      experimental setups ultimately led to a few general recommendations. With respect
      to the routinely used commercial Sherlock Microbial Identification System (MIS,
      Microbial ID, Inc. (MIDI), Newark, Delaware, USA), the artificial neural network
      test results showed a significant improvement in Bacillus species identification.
      These results indicate that machine learning techniques such as artificial neural
      networks are most promising tools for FAME-based classification and
      identification of bacterial species.

PMID- 18322820
TI  - Imagining human enhancement: whose future, which rationality?
AB  - This article critically evaluates bettering human life. Because this involves
      lives that do not exist yet, the article investigates human eugenics and
      enhancement through the social prism of 'the imaginary' (defined 'as a set of
      assumptions and concepts for thinking and speaking about human enhancement and
      its future direction') [1]. "Exploring basic assumptions underlying the idea of
      human enhancement" investigates underlying assumptions and claims for human
      enhancement. Firstly, human eugenics and enhancement entangles a factual as well
      as a normative claim about what improvement/betterment maybe constitutive of.
      Secondly, claims about what a better life is, is often a future orientated claim
      about whether certain kinds of life that do not exist yet should ever exist.
      Moral images of thought are introduced and how they work to make normative
      judgments about lives that do not exist. This implicates the moral problem of
      difference, where an image of a 'better' life-classically expressed in eugenics
      as a 'superior' and/or 'normal' life-necessarily entails inferiority and/or
      deviance from a norm. "Moral imagination in contemporary fiction and the history
      of old eugenics", introduces moral images in history of eugenics and demonstrates
      how examples fall foul of the problem. "The new (liberal) eugenics and the moral
      image of therapy" examines progress in contemporary debates, the move from
      authoritarian to non-authoritarian eugenics (human enhancement), and how, to some
      extent, this has solved the problem of difference, through liberal defence of
      personal choice. "The heart of the eugenic issue" suggests that personal choice
      in liberal non-authoritarian eugenics is not immune to basic drive behind all
      eugenic arguments; desire as lack which is expressed as the continual
      dissatisfaction of not having our future expectations met.

PMID- 18322821
TI  - The limits of objective assessment of medical practice.
AB  - Medical work is increasingly being subjected to objective assessment as those who
      pay for it seek to grasp the quality of that work and how best to improve it.
      While objective measures have a role in the assessment of health care, I argue
      that this role is currently overestimated and that no human practice such as
      medicine can be fully comprehended by objective assessment. I suggest that the
      character of practices, in which formalizations are combined with judgment,
      requires that valid assessment involve the perspective of the skilled
      practitioner. Relying exclusively on objective measures in assessing health care
      will not only distort our assessments of it but lead to damage as the incentives
      of health care workers are directed away from the important aspects of their work
      that are not captured by objective measures.

PMID- 18322822
TI  - ID2 promotes the expansion and survival of growth-arrested pancreatic beta cells.
AB  - Inhibitors of DNA binding proteins (Ids) are implicated in the control of
      proliferation and differentiation. Herein, we tested the hypothesis that Id2
      could stimulate proliferation and survival in differentiated pancreatic beta
      cells. We showed that Id2-enhanced proliferation of a growth-arrested pancreatic
      beta cell line (BTC-tet). This was mediated by the Rb pathway, as shown by an
      E2F1-driven reporter assay and Western immunoblot of phosphorylated Rb protein.
      Id2 also induced expression of Bcl-2, accompanied by a significant reduction of
      critical mediators of cytokine stimulation, including p38 MAPK and NFkappaB, as
      well as apoptosis markers, caspase-3 and Annexin-V. Overall, our data suggest
      that Id2 enhances proliferation and survival of growth-arrested BTC-tet cells.

PMID- 18322823
TI  - Expression of Id1 in adult, regenerating and developing pancreas.
AB  - Several key transcription factors are necessary for alpha cell development in the
      pancreas. In this study, we describe the expression of Inhibition of DNA-binding
      protein 1 (Id1) in the developing as well as the normal adult pancreas. We found
      co-expression of Id1 with bone morphogenetic protein (BMP) receptor in alpha
      cells. Inhibition of BMP4 signaling with a specific neutralizing antibody
      slightly decreases the proportion of glucagon cells in the adult pancreas but had
      a significant effect in a model of pancreas regeneration. In late embryonic
      pancreas, Id1 co-localized with GATA4, a transcription factor known for its
      critical function in glucagon cell development. However, in early postnatal
      period, the expression of Id1 and GATA4 diverged with Id1 identified in glucagon
      cells and GATA4 restricted to the acinar pancreas.

PMID- 18322824
TI  - An epidermal growth factor-like repeat of Del1 protein increases the efficiency
      of gene transfer in vitro.
AB  - In this paper, we found that Del1, an extracellular matrix protein secreted by
      embryonic endothelial cells, increases the efficiency of transfection in vitro.
      Conditioned medium containing Del1 increased transfection by the LacZ gene using
      several non-viral gene transfer systems, including lipoplex and polyplex methods.
      Experiments using deletion mutants and fragments of Del1 revealed that the third
      epidermal growth factor-like repeat (E3) of Del1 mediates the enhancement of gene
      transfer and, furthermore, that the motif CXDXXXFXCXC is essential. Incubation of
      Pro5 cells, a yolk sac-derived cell line, with as low as 16 pM recombinant E3 was
      sufficient to enhance transfection, and 1 nM recombinant E3 enhanced the
      transfection 12-fold. Inhibitors of endocytosis suppressed this activity of the
      recombinant E3. These results suggest that the E3 fragment of Del1 can be used as
      a general biological enhancer of non-viral gene transfer.

PMID- 18322825
TI  - [Neurological symptoms and disability in HTLV-1 associated myelopathy].
AB  - INTRODUCTION: The human T cell lymphotropic virus type I (HTLV-I) is a retrovirus
      that causes tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM).
      Objectives. To describe neurological characteristics and the severity of
      disability in a sample of patients with TSP/HAM. METHODS: All TSP/HAM patients
      consecutively admitted during 2006 at the Brasilia Sarah Hospital, neurology
      outpatient clinic were included in the study. HTLV-I infected patient fulfilled
      criteria for serological positivity at both ELISA and western blot. Ashworth
      spasticity scale, Barthel index of activities of daily living, kurtzke functional
      systems and the Expanded Disability Status Scale (EDSS) were applied. All
      patients performed electrophysiological studies (evoked potentials,
      electromyogram) and brain/spinal cord magnetic resonance imaging (MRI). RESULTS:
      Forty two of 249 paraparetic patients (16.9%; 26 females; mean age: 49.8 years)
      were diagnosed as having TSP/HAM. Mean time of evolution was 11.2 years. Most
      common neurological syndrome was a chronic progressive spastic paraparesis with
      hyperreflexia, ankle clonus and bilateral Babinski sign (97.7 %). Other findings
      were proximal muscle atrophy in lower limbs (28.6 %) , ataxia (21.4%), and
      peripheral neuropathy (7.1%). Half of patients were wheel-chair restricted or had
      a domiciliary walk. EDSS median was 6 and Barthel index mean score was 65. Most
      common findings on spinal cord MRI were thoracic spinal cord atrophy (66.7%) and
      white matter hyper-intensity areas in cerebral subcortical (42.8 %) and spinal
      cord (21.4%) regions. CONCLUSIONS: TSP/HAM is a very disabilitating disorder.
      Peripheral neuropathy and ataxia are other syndromes that should be included in
      the spectrum of HTLV-I infection.

PMID- 18322826
TI  - [Epidural spinal abscesses. Review of a clinical serie].
AB  - INTRODUCTION: The spinal abscess is an infrequent infectious complication whose
      diagnosis is often delayed, therefore bringing about significant morbidity and
      death rates. In the last years, its incidence has raised progressively. The
      objective of this work is to present the clinical features of a series of spinal
      abscesses. METHOD: The clinical histories of all patients diagnosed of spinal
      cord abscess were evaluated retrospectively. RESULTS: We obtained seven cases,
      with a 5/2 male/female proportion, all subjects being over 50 years old.
      Incidence was 0.58/10,000 admissions per year. All patients debuted with local
      pains, but only 6/7 (90%) had fever. Focal neurological signs appeared in all
      patients within the first 0-5 day-period; they were weakness (86%) and sensitive
      alterations (43%). The most frequent germ was Staphylococcus aureus ( 5 0%).
      Diabetes mellitus existed in 5/7 cases (71.5%). Four patients were treated by
      surgery; three of them (75%) had flaccid motor deficit as sequel and the other
      died. Medical treatment alone was maintained in 3/7 (43%); two experienced
      partial improvement without recovery of the motor functions and another died.
      CONCLUSIONS: Spinal epidural abscess is a rare, although serious, disease. For
      this reason, we should maintain a high level of suspicion when a patient has
      spinal or radicular pain associated with systemic symptoms such as fever or
      deterioration in the general state of health, especially in patients >50 years
      under weakening situations.

PMID- 18322827
TI  - [Usefulness of the 14-3-3 test for the diagnosis of sCJD evaluated by a Spanish
      reference center].
AB  - INTRODUCTION: The performance of the 14-3-3 protein test has been shown to be
      adequate for sporadic Creutzfeldt-Jakob disease (sCJD) diagnosis in selected
      populations, but its routine validity has been questioned. METHODS: One thousand
      and sixty-eight patients with clinically suspected sCJD were analyzed in a
      Spanish reference center. In order to explore the influence of the clinical
      context on the performance of the immunoassay, the patients were classified at
      sample reception according to the World Health Organization (WHO) diagnostic
      criteria excluding the 14-3-3 test results. The yield of the immunoassay was
      evaluated in each subgroup with criteria of probable, possible sCJD or non-sCJD.
      RESULTS: In the set of patients with suspicion of sCJD the inclusion of the 14-3
      3 test produces a significant increase in the diagnosis certainty (positive
      likelihood ratio: 10.1) compared to the WHO's criteria, excluding the 14-3-3
      test. For patients classified at sample reception as probable sCJD (n=166),
      possible sCJD (n=129) and non-sCJD (n=773), the positive predictive values for
      the test were 98.4%, 97.5% and 31%, and the negative predictive values were
      22.2%, 73.4% and 100%, respectively. CONCLUSIONS: The predictive values of the
      assay vary according to the previous diagnostic certainty. Therefore, in order to
      interpret correctly the test, it is necessary to evaluate the degree of initial
      clinical suspicion of the patient at the moment of the cerebrospinal fluid (CSF)
      extraction. This study offers up-to-date information, referenced to the Spanish
      population, and in useful format, and it is intended to serve as a guideline for
      14-3-3 test results interpretation to the clinicians in our community.

PMID- 18322828
TI  - [Polysomnography in the neurology patient].
AB  - The polysomnography is a standardized diagnostic tool in neurology. It is used to
      study sleep structure and can diagnose many sleep disorders. Since this test is
      not always adequately available as it is a complex test that requires a qualified
      team and staff, its most necessary and urgent indications should be stressed in
      order to thus avoid the waiting lists. In this paper we review the primary
      indications of the nocturnal sleep studies in the different groups of
      neurological disorders. We review the bibliography, selecting the papers that
      help to specify when the polysomnographic study would be indicated and those
      situations in which it may be indispensable or urgent.

PMID- 18322829
TI  - [Cerebral gliomatosis].

PMID- 18322830
TI  - [Familial glioma].

PMID- 18322831
TI  - [Kluver-Bucy syndrome. Seven year follow-up of one patient].
AB  - OBJECTIVE: To present a left-handed patient who had an acute encephalopathy,
      possibly of viral etiology, followed by remote and recent memory loss, several
      types of apraxia and emotional disturbance, without any motor abnormalities. He
      had cerebral lesions that involved both temporal lobes and other brain regions.
      All features corresponded to the Kluver-Bucy syndrome. After a seven year follow
      up, no improvement of the neurological and neuroradiological, mainly by magnetic
      resonance imaging (MRI) features was observed. CASE REPORT: A 14 year-old left
      handed boy suffered sudden onset of fever (40.4 degrees C), headache, vomiting,
      focal and generalized seizures and coma. After the acute illness, the patient had
      severe neurological sequels consisting in total loss of memory without any
      capacity to recognize persons (including family members) and remote events and he
      was not capability of remember hardly anything that he was taught after his
      disease, these alterations continued almost completely during the seven years
      (from 14 to 21 years) that we followed him up. The only abilities that he
      conserved in similar conditions to those prior to his acute disease were his
      capacity to swim (including the style of jumping into the water), bike riding,
      playing football, dominoes, cards, etc., which he had learned during his
      childhood, to say the numbers and the alphabet letters rapidly by heart (without
      knowing them) and to avoid cars on the street. MRI showed post-inflammatory
      lesions in the temporal and the parieto-temporo-occipital regions bilaterally
      (cortical and subcortical regions) and in the left occipital region. He presented
      almost all types of apraxia. CONCLUSION: Kluver-Bucy syndrome, which can be
      secondary to more than 50 different causes, not only presents remote memory loss
      but also recent memory loss as in our patient, who appeared to be isolated from
      the surrounding world. Motor function and automated activities learned before the
      acute brain illness were not affected and could be recovered. Etiology, location
      and extent of the anatomic brain lesion appear to be the most important
      prognostic conditions.

PMID- 18322832
TI  - [L-dopa sensitive Parkinsonism in neurocysticercosis].
AB  - INTRODUCTION: Neurocysticercosis (NC) is a chronic parasitary disease that may
      have different neurological manifestations, such as seizures, dementia or
      obstructive hydrocephalus. On rare occasions, pictures secondary to hydrocephalia
      may occur with Parkinsonian syndrome. CASE REPORT: We present the case of a 29
      year old woman with serologically confirmed NC and obstructive hydrocephalia
      secondary to a cyst in the IV ventricle. The patient required repeated ventricle
      peritoneal shunt replacement because of valvular malfunction and obstructive
      hydrocephalia. She developed Parkinsonian's syndrome, which subsided after
      combined treatment with cysticidal drugs and L-dopa. DISCUSSION: Parkinsonian
      syndrome is an atypical presentation in NC. In this case, the above-mentioned
      profile is found within the context of multiple valvular malfunctions who nature
      is reversible after appropriate treatment. It seems to be related with increases
      in intraventricular cerebrospinal fluid pressure. We can conclude that
      Parkinsonian syndromes may be one more expression of NC. This acquires greater
      importance according to its context, in addition to the limited presence of
      similar cases in our environment in the literature.

PMID- 18322833
TI  - [Primary cerebral lymphoma in an immunocompetent patient].
AB  - Primary lymphoma of the central nervous system PLCNS) was a very uncommon disease
      until a few decades ago. However, its incidence has increased in recent years,
      mainly in immunocompetent patients. Thus, some authors suggest that PLCNS may
      become the most frequent tumor. The final diagnosis is based on the pathology
      study of the samples obtained with stereotaxic biopsy or with surgery, but X-ray
      studies may be very useful in the orientation of this disease. The typical
      finding in immunocompetent subjects is the appearance of single supratentorial
      lesions with homogeneous uptake of contrast and scarce edema, without edema,
      necrosis nor bleeding. Survival has increased thanks to the new treatments
      applied, although there is still controversy regarding frequency, dose and
      administration form of many of them. We present the case of an immunocompetent
      male patient with progressive dyplopia and vertigo caused by a primary lymphoma
      of the central nervous system and a review the literature.

PMID- 18322834
TI  - [Neuroscientists in the Third Reich].
AB  - INTRODUCTION: This article analyzes the effects that the arrival of the nazis to
      power as well as the participation of the neuroscientists in the programs
      developed by nazi medicine had on german neurology. METHODS: Review of the
      literature related with medicine in the times of the nazis, placing special
      attention on the role played by the neuroscientists. RESULTS: The physicians were
      the professional group that joined the nazi party the most. Many neurologists,
      psychiatrists and neuropathologists participated in the sterilization, euthanasia
      and experimenting programs in humans. Based on the experience acquired in these
      projects, some were chosen as personnel in charge of extermination in the
      concentration camps. Eminent neurologists such as Hallervorden, Spatz and
      Schaltenbrand took advantage of the scientific possibilities offered by the
      euthanasia and experimentation projects in humans with no harm being done to
      their careers after the war. Many Jewish neurologist or dissidents were driven
      out of their work, required to go into exile or, in the worst of the cases, were
      jailed and assassinated. CONCLUSIONS: The nazi government had two outstanding
      effects on german neurology. On the one hand, many neurologists were harmed due
      to racial or political reasons. On the other, outstanding neurologists
      participated in programs of nazi medicine. This reminds us of the perverse role
      that politics may play in medicine and that scientific knowledge should not
      forget ethics.

PMID- 18322835
TI  - [Steinert's myotonic dystrophy in a portrait in the Prado Museum].

PMID- 18322836
TI  - [Reversible posterior leukoencephalopathy: the guilty list is increasing].

PMID- 18322843
TI  - Synthesis of novel derivatives of bispodophyllotoxin as potential antineoplastic
      agents--part XVI.
AB  - Podophyllotoxin and related analogs present numerous challenges associated with
      optimal antitumor activity and severe unpredictable toxicity. In an attempt to
      find biorational podophyllotoxin-related drug, two moieties of podophyllotoxin
      have been linked at C4-position by a simple modification of the carbodiimide
      procedure to provide novel bispodophyllotoxin analogs (4a-4e) and their
      structural information was extensively characterized by using 1H-NMR, IR, and
      HRMS.

PMID- 18322844
TI  - A new diaryheptanoid from the bark of Myrica rubra.
AB  - A new diarylheptanoid, (11 xi)-3,5-dimethoxy-11,17-dihydroxy-4,19-diketo-[7,0]
      metacyc- lophane, named as rubanol 1, was isolated from the bark of Myrica rubra
      along with four known compounds (2-5). Their structures were determined by
      spectroscopic methods including 1D, 2D NMR or comparison with authentic samples.
      Compound 1 exhibited cytotoxicity against Lun-06, Neu-04, and Bre-04 cell lines
      with GI50 values of 16.03-32.58 microg mL(-1).

PMID- 18322845
TI  - Spathoside, a cerebroside and other antibacterial constituents of the stem bark
      of Spathodea campanulata.
AB  - Spathoside, a new cerebroside was isolated from the stem bark of Spathodea
      campanulata, besides known compounds (n-alkanes, linear aliphatic alcohols,
      sitosterol and their esters, beta-sitosterol-3-O-beta-D-glucopyranoside,
      oleanolic acid, pomolic acid, p-hydroxybenzoic acid and phenylethanol esters).
      The structures of the isolated compounds were established by spectroscopic
      studies. The antibacterial activity of the isolated compounds against a wide
      range of microorganisms was examined. They inhibited significantly the growth of
      some gram-positive and -negative bacteria.

PMID- 18322846
TI  - Novel class of hybrid natural products derived from lupeol as antimalarial
      agents.
AB  - Thirty-four novel hybrid lupeol derivatives (4-18) were prepared and evaluated
      for antimalarial activity in vitro against Plasmodium falciparum. Three compounds
      (13d, 16a and 17a) have shown antimalarial activity at lower dose (10 microg mL(
      1)) than lupeol.

PMID- 18322847
TI  - A new triterpenoid saponin from Gleditisia sinensis and structure-activity
      relationships of inhibitory effects on lipopolysaccharide-induced nitric oxide
      production.
AB  - A phytochemical investigation of the anomalous fruits of Gleditisia sinensis led
      to one new oleanane-type triterpenoid saponin acylated with one monoterpenic
      acid, 3-O-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-xylopyranosyl-(1 -->
      3)-beta-D-xylopyranosyl-(1 --> 4)-alpha-L-rhamnopyranosyl-(1 --> 2)-[(6S,2E)-6
      hydroxy-2,6-dimethyl-2,7-octadienoyl-(1 --> 6)]-beta-D-glucopyranosyl ester,
      named gleditsioside Z (1), together with nine known ones (2-10). Their structural
      details were mainly established on the basis of 1D, 2D NMR and HR-MS analysis as
      well as some chemical methods. Structure-activity relationships of the isolated
      saponins that affected nitric oxide production from cultured mouse macrophages
      (RAW 264.7 cell lines) induced by lipopolysaccharide were discussed.

PMID- 18322848
TI  - Antimicrobial and antileishmanial xanthones from the stem bark of Allanblackia
      gabonensis (Guttiferae).
AB  - The phytochemical study of stem bark of Allanblackia gabonensis has resulted in
      the isolation and characterisation of one new xanthone derivative, named
      allanxanthone D, together with 10 known compounds, including 6 xanthones
      derivatives, allanxanthone A, 1,5-dihydroxyxanthone, 1,7-dihydroxyxanthone and
      1,3,6,7-tetrahydroxy-2-(3-methylbut-2-enyl)xanthone, forbexanthone, 6
      deoxyisojacareubin, one polyisoprenylated benzophenone, guttiferone F, one
      flavanol, epicathechin, two phytosterols, beta-sitosterol and campesterol. The
      structures of these compounds were established on the basis of one- and two
      dimensional NMR homo- and hetero-nuclear evidence. These compounds were evaluated
      for their activity against Leishmania amazonensis in vitro and antimicrobial
      activities against a range of Gram negative and Gram positive bacteria.

PMID- 18322849
TI  - Macrolactin S, a novel macrolactin antibiotic from marine Bacillus sp.
AB  - A new 24-membered ring lactone, macrolactin S, was isolated from a culture broth
      of marine Bacillus sp. and its structure was established by various spectral
      analyses. Macrolactin S is the first macrolactin hydroxylated at C-12. Besides,
      the known compounds macrolactin A and macrolactin B were also isolated, which
      were elucidated on the basis of spectral data analyses and literature data
      comparison. They exhibited antibacterial activity against E. coli and S. aureus.

PMID- 18322850
TI  - A new compound against Peries rapae from Stellera chamaejasme.
AB  - The ethanol extract of Stellera chamaejasme roots exhibited significant
      bioactivity against Peries rapae. In the course of a search for the active
      compounds, S-(+)-1,5-diphenyl-3-hydroxy-1-pentanone (1) was isolated and this
      compound has never been found before in S. chamaejasme as far as we known. The
      structure was established on the basis of various spectral data, including IR,
      UV, 1H NMR, 13C NMR, EIMS, and chemical synthesis. Mortality against P. rapae was
      also determined.

PMID- 18322851
TI  - Chemical constituents with antibacterial activity from Euphorbia sororia.
AB  - A group of ceramide (1) was isolated from the aerial parts of Euphorbia sororia.
      On the basis of spectroscopic data, chemical methods and GC-MS analysis, the
      structure of 1 was characterised as (2S,3S,4R,8E)-2-(eicosanoyl approximately
      octacosanoyl amino)-1,3,4-octadecanetriol-8-ene. In addition, four known ellagic
      acid derivatives 3,3'-di-O-methylellagic acid (2), 3,3',4'-tri-O-methylellagic
      acid (3), 4-O-sulfooxy-3,3'-di-O-methylellagic acid (4) and 4-O-sulfooxy- 3,3',4'
      tri-O-methylellagic acid (5) were isolated from the plant. Biological screening
      of all compounds revealed moderate antibacterial activity.

PMID- 18322852
TI  - A rapid method for the quantification of artemisinin in Artemisia annua L. plants
      cultivated for the first time in Burundi.
AB  - We describe a simple, rapid combined method for extracting the antimalarial
      compound artemisinin from the leaves of Artemisia annua L. cultivated for the
      first time in Burundi, and quantitating the active principle by high-performance
      liquid chromatography-electrospray mass spectrometry.

PMID- 18322853
TI  - Separation and identification of botanical insecticide 7-hydroxycoumarin and its
      biological activity against Aphis craccivora and Culex pipiens pallens.
AB  - The root powder of Stellera chamaejasme was extracted with chloroform. The crude
      extract obtained was chromatographed with silica gel columns many times. One pure
      natural product was obtained. It was identified as 7-hydroxycoumarin. Laboratory
      bioassay showed that it had a good insecticidal activity against Aphis craccivora
      and Culex pipiens pallens. Its median lethal concentrations (LC50) (24 h after
      treatment) were 19.56 and 0.435 mg L(-1), respectively. The results of regressive
      and correlative analysis demonstrated that the correlations were very significant
      between concentration and efficacy. The corresponding correlative coefficients
      were 0.9686 and 0.9712, respectively. This is the first report of the
      insecticidal activity of 7-hydroxycoumarin. It may represent a new class of
      insecticides.

PMID- 18322854
TI  - Apple pomace: a versatile substrate for biotechnological applications.
AB  - Apple pomace is the processing waste generated after apple juice manufacturing
      and represents up to 30% of the original fruit. This solid residue consists of a
      complex mixture of peel, core, seed, calyx, stem, and soft tissue. This residual
      material is a poor animal feed supplement because of its extremely low protein
      content and high amount of sugar. The application of agroindustrial by-products
      in bioprocesses offers a wide range of alternative substrates, thus helping solve
      pollution problems related to their disposal. Attempts have been made to use
      apple pomace to generate several value-added products, such as enzymes, single
      cell protein, aroma compounds, ethanol, organic acids, polysaccharides, and
      mushrooms. This article reviews recent developments regarding processes and
      products that employed apple pomace as a substrate for biotechnological
      applications.

PMID- 18322855
TI  - Melon fruits: genetic diversity, physiology, and biotechnology features.
AB  - Among Cucurbitaceae, Cucumis melo is one of the most important cultivated
      cucurbits. They are grown primarily for their fruit, which generally have a sweet
      aromatic flavor, with great diversity and size (50 g to 15 kg), flesh color
      (orange, green, white, and pink), rind color (green, yellow, white, orange, red,
      and gray), form (round, flat, and elongated), and dimension (4 to 200 cm). C.
      melo can be broken down into seven distinct types based on the previously
      discussed variations in the species. The melon fruits can be either climacteric
      or nonclimacteric, and as such, fruit can adhere to the stem or have an
      abscission layer where they will fall from the plant naturally at maturity.
      Traditional plant breeding of melons has been done for 100 years wherein plants
      were primarily developed as open-pollinated cultivars. More recently, in the past
      30 years, melon improvement has been done by more traditional hybridization
      techniques. An improvement in germplasm is relatively slow and is limited by a
      restricted gene pool. Strong sexual incompatibility at the interspecific and
      intergeneric levels has restricted rapid development of new cultivars with high
      levels of disease resistance, insect resistance, flavor, and sweetness. In order
      to increase the rate and diversity of new traits in melon it would be
      advantageous to introduce new genes needed to enhance both melon productivity and
      melon fruit quality. This requires plant tissue and plant transformation
      techniques to introduce new or foreign genes into C. melo germplasm. In order to
      achieve a successful commercial application from biotechnology, a competent plant
      regeneration system of in vitro cultures for melon is required. More than 40 in
      vitro melon regeneration programs have been reported; however, regeneration of
      the various melon types has been highly variable and in some cases impossible.
      The reasons for this are still unknown, but this plays a heavy negative role on
      trying to use plant transformation technology to improve melon germplasm. In
      vitro manipulation of melon is difficult; genotypic responses to the culture
      method (i.e., organogenesis, somatic embryogenesis, etc.) as well as conditions
      for environmental and hormonal requirements for plant growth and regeneration
      continue to be poorly understood for developing simple in vitro procedures to
      culture and transform all C. melo genotypes. In many cases, this has to be done
      on an individual line basis. The present paper describes the various research
      findings related to successful approaches to plant regeneration and transgenic
      transformation of C. melo. It also describes potential improvement of melon to
      improve fruit quality characteristics and postharvest handling. Despite more than
      140 transgenic melon field trials in the United States in 1996, there are still
      no commercial transgenic melon cultivars on the market. This may be a combination
      of technical or performance factors, intellectual property rights concerns, and,
      most likely, a lack of public acceptance. Regardless, the future for improvement
      of melon germplasm is bright when considering the knowledge base for both
      techniques and gene pools potentially useable for melon improvement.

PMID- 18322856
TI  - Properties, potentials, and prospects of antifreeze proteins.
AB  - Antifreeze proteins (AFPs) are a group of proteins that protect organisms from
      deep freezing temperatures and are expressed in vertebrates, invertebrates,
      plants, bacteria, and fungi. The nuclear magnetic resonance, x-ray structure, and
      many spectroscopic studies with AFPs have been instrumental in determining the
      structure-function relationship. Mutational studies have indicated the importance
      of hydrophobic residues in ice binding. Various studies have pointed out that the
      mechanism of AFP action is through its adsorption on the ice surface, which leads
      to a curved surface, preventing further growth of ice by the "Kelvin effect." The
      AFPs have potential industrial, medical, and agricultural application in
      different fields, such as food technology, preservation of cell lines, organs,
      cryosurgery, and cold hardy transgenic plants and animals. However, the
      applications of AFPs are marred by high cost due to low yield. This review deals
      with the source and properties of AFPs from an angle of their application and
      their potential. The possibility of production using different molecular
      biological techniques, which will help increase the yield, is also dealt with.

PMID- 18322857
TI  - Investigating the role of hypothalamic paraventricular nucleus in nociception of
      the rat.
AB  - The role of hypothalamic paraventricular nucleus (PVN) in nociception was
      investigated in the rat. Electrical stimulation of the PVN increased pain
      threshold, and microinjection of L-glutamate sodium into the PVN also elevated
      pain threshold in a dose-dependent manner, whereas cauterization of the PVN
      decreased pain threshold. Stimulation or cauterization of the area located within
      1.0 mm of the outer perimeter of the PVN did not change pain threshold. Pituitary
      removal could not influence the effect of L-glutamate sodium microinjection into
      PVN-induced pain threshold increase. The data suggest that PVN plays a role in
      antinociception through the central nervous system rather than peripheral organs.

PMID- 18322858
TI  - The effects of modafinil, caffeine, and dextroamphetamine on judgments of simple
      versus complex emotional expressions following sleep deprivation.
AB  - Cognitive abilities such as vigilance, attention, memory, and executive
      functioning can be degraded significantly following extended periods of
      wakefulness. Although much evidence suggests that sleep-loss induced deficits in
      alertness and vigilance can be reversed or mitigated by stimulants such as
      caffeine, it is not clear how these compounds may affect other higher level
      cognitive processes such as emotional perception and judgment. Following 47 h of
      sleep deprivation, the study examined the effect of three stimulant medications
      (modafinil 400 mg, dextroamphetamine 20 mg, caffeine 600 mg) or placebo on the
      ability of 54 healthy participants to discriminate and label simple emotional
      expressions versus complex affect blends (created by morphing photographs of two
      different affective facial expressions). For simple affective faces, neither
      sleep loss nor stimulant medications made any difference on the accuracy of
      judgments. In contrast, for complex emotion blends, all three stimulant
      medications significantly improved the ability to discriminate subtle aspects of
      emotion correctly relative to placebo, but did not differ from one another. These
      findings suggest that all three stimulant medications are effective at restoring
      some aspects of subtle affective perception.

PMID- 18322859
TI  - Involvement of amlodipine, diazoxide, and glibenclamide in development of
      morphine tolerance in mice.
AB  - In this study, the effects of the calcium channel blocker (amlodipine), potassium
      channel opener (diazoxide), and potassium channel blocker (glibenclamide) on the
      development of morphine-induced tolerance in the formalin test was investigated.
      During development of tolerance to morphine, intraperitoneal (i.p.)
      administration of different doses of amlodipine (5, 7.5 and 10 mg/kg) or
      diazoxide (1, 5 and 10 mg/kg) in combination with morphine (20 and 30 mg/kg)
      increased tolerance in the first and second phase of the test. However,
      glibenclamide (2.5, 5, and 10 mg/kg) decreased morphine tolerance in the second
      phase of formalin test. It is concluded that calcium and potassium channel
      mechanisms may be involved in the morphine tolerance.

PMID- 18322860
TI  - What aspect of handedness is general motor programming related to?
AB  - As general motor programming had previously been found to be related to
      consistency of hand preference (Keane, 1999), the present study attempted to
      elucidate what general motor programming involves by reinvestigating responses to
      the Edinburgh Handedness Inventory in order to see if there was some consensus
      with regards to the items that tended to differentiate the consistent handers
      from the inconsistent handers. It was found that the opening a box item did
      differentiate the consistent handers from the inconsistent handers. Control of
      this type of bimanual task seems to be specifically related to the general motor
      programmer, and not hand preference as such.

PMID- 18322861
TI  - Influence of central nicotinic receptors on arachidonylcyclopropylamide (ACPA)
      induced antinociception in mice.
AB  - The nicotinic cholinergic receptors have been reported to be involved in several
      actions of cannabinoids (e.g., bradycardia, hypothermia). However, the influence
      of central cholinergic system on cannabinoids antinociceptive effect has not been
      reported. This study investigated the possible part played by nicotinic
      cholinergic modulator drugs on the antinociceptive effect of central
      administration of arachidonylcyclopropylamide (ACPA) in mice. The antinociceptive
      effects of intracerebroventricular (i.c.v.) administration of ACPA using the
      formalin test have been studied in mice. The effects of nicotine or mecamylamine
      (a nicotinic cholinergic antagonist) on ACPA analgesia are also studied. i.c.v.
      administration of ACPA (0.004-1 microg/mice) induced antinociceptive effect in
      mice. i.c.v. administration of nicotine (0.1 or 0.5 microg/mice) or mecamylamine
      (2 microg/mice) potentiated or antagonized ACPA antinociceptive effects,
      respectively. It is concluded that ACPA-induced analgesia is influenced by
      central nicotinic cholinergic activity.

PMID- 18322862
TI  - Macrodystrophia lipomatosa with multiple entrapment neuropathies: a case report.
AB  - Macrodystrophia lipomatosa is a rare nonhereditary congenital malformation that
      mainly affects mesenchymal structures. The pathology is associated with
      hypertrophic fibro-adipose tissues. One or more of the digits of the extremities
      are affected. This condition is previously described as macrodactyly,
      megalodactyly, or localized gigantism. This article describes a 48-year-old male
      patient who presented with the enlargement of unilateral (right) lower limb,
      especially of the first toe and tarsal tunnel syndrome. Although there is no
      clinically significant involvement of the upper extremities, bilateral cubital
      and unilateral carpal tunnel syndromes were also detected and macrodystrophia
      lipomatosa with multiple entrapment neuropathies was diagnosed in the patient.

PMID- 18322863
TI  - Local transcutaneous cooling of the spinal cord in the rat: effects on long-term
      outcomes after compression spinal cord injury.
AB  - This study tested efficiency of a novel thermoelectric cooler for local
      transcutaneous spinal cord cooling. Spinal cord compression was made by epidural
      balloon inflation at T8-T9 level of the spinal cord. Experimental animals (n=20)
      were divided into two groups. In the hypothermic group, local cooling started 25
      min after spinal cord injury and lasted for 1 h with paravertebral temperature
      maintained at 28.5 degrees C (+/-0.3). Normothermic group underwent identical
      procedures, but their temperature was maintained normothermic. The assessment of
      neurologic recovery was performed once a week during a 4 weeks survival period.
      After 4 weeks animals were sacrificed and the extent of the spinal cord lesion
      morphometrically evaluated. There were no statistically significant intergroup
      differences in BBB scores and preserved volumes of the spinal cord tissue. In
      consecutive cross-sectional areas, hypothermic animals had significantly more
      preserved white matter at the cranial periphery of the lesion. It was concluded
      that mild posttraumatic hypothermia (31.8 degrees C) had some protective effect
      on tissue loss after spinal cord injury but this effect was not associated with
      functional improvement.

PMID- 18322864
TI  - Memory tests in subgroups of adult attention deficit hyperactivity disorder
      reveals simultaneous capacity deficit.
AB  - Neuropsychological tests were used to evaluate different memory systems in the
      three subgroups of adult Attention Deficit Hyperactivity Disorder (ADHD) (n=105)
      using analysis of means, factor analysis, and GLM analysis with covariance of
      gender, estimated IQ, and level of anxiety and depression measured with the
      Hospital anxiety and depression scale. A higher IQ level was found in the
      neuropsychological background tests for the predominantly inattentive subtype
      (ADD). In the memory tests the dual-task memory/simultaneous capacity tests
      "Brown-Peterson" Consonant Trigram and Benton Visual Retention Test (BVRT) were
      the most sensitive and were severely reduced in all three subgroups, but only the
      BVRT revealed a difference between the three ADHD groups. In learning and delayed
      recall measured with Rey Auditory Verbal learning test and modified Diagnosticum
      fur Cerebralschadigung (mDCS), the Attention Deficit Disorder subgroup had the
      best learning and delayed capacity of the three groups. A good agreement was
      found between the interviewed DSM-IV-TR criteria, Conners CAARS S:S scale, and
      Wender WURS 25-item scales. Despite the difference in number of ADHD criteria for
      the three ADHD subgroups, the results in the neuropsychological memory tests
      indicate a severe reduction in all three subgroups of adult ADHD in simultaneous
      capacity.

PMID- 18322865
TI  - Changes in memory performance, heart rate, and blood oxygen saturation due to 30%
      oxygen administration.
AB  - This study investigated the effect of 30% oxygen administration on memory
      cognitive performance, blood oxygen saturation, and heart rate. Ten healthy male
      and female college students (male: 25.8+/-0.8 years, female: 24.2+/-1.9 years)
      participated in the study. The results of the memory performance analysis reveal
      that word recall rates were enhanced with 30% oxygen administration compared to
      21% oxygen. When 30% oxygen was supplied, blood oxygen saturation was increased
      and heart rate was decreased compared to that with 21% oxygen administration.
      Significant positive correlations were found between changes in oxygen saturation
      and heart rate and memory performance. This result supports the hypothesis that
      30% oxygen administration would lead to increases in memory performance.

PMID- 18322866
TI  - Health effects of atmospheric particulates: a medical geology perspective.
AB  - In this review, atmospheric particulates as composite airborne earth materials
      often containing both natural and anthropogenic components were examined in the
      context of medical geology. Despite a vast number of both experimental and
      epidemiological studies confirming the direct and indirect links between
      atmospheric particulates and human health, the exact nature of mechanisms
      affecting the particulate-induced pathogenesis largely remains unexplored. Future
      in depth research on these areas would be most successful if potential mechanisms
      are examined with reference to the physical (e.g., size, shape and surface),
      chemical, mineralogical and source characteristics of particulate matters. The
      underlying goal of this review was to present the relevant terminology and
      processes proposed in the literature to explain the interfaces and interactions
      between atmospheric particles and human body within the framework of "atmospheric
      particle cycles." The complexities of the interactions were demonstrated through
      case studies focusing on particulate matter air pollution and malignant
      mesothelioma occurrences due to environmental exposure to erionite-a fibrous
      zeolite mineral. There is an urgent need for a standard protocol or speciation
      methods applicable to earth-materials to guide and streamline studies on etiology
      of mineral-induced diseases. This protocol or speciation methods should provide
      relevant procedures to determine the level and extent of physical, chemical and
      mineralogical heterogeneity of particulate matters as well as quantitative in
      situ particulate characteristics.

PMID- 18322867
TI  - Regulatory assessment of chemicals within OECD member countries, EU and in
      Russia.
AB  - The chemical risk assessment is essesntial part of new chemical legislation
      registration, evaluation, and authorization of chemicals (REACH). The article
      presents a review of chemical legislation policies in the European Union (EU) and
      in Russia, and changes in chemicals regulations to meet the requirement of REACH.
      The risk assessment paradigm, toxicological parameters, safe limits and
      classification criteria used by different agencies and authorities in different
      countries are reported. Our investigation also focuses on comparison of chemical
      risk assessment criteria used in OECD member countries and in Russia. Tendencies
      in harmonization in accordance with the globally harmonized system of
      classification and labeling of chemicals (GHS) are discussed.

PMID- 18322868
TI  - Toxicity of kava kava.
AB  - Kava is a traditional beverage of various Pacific Basin countries. Kava has been
      introduced into the mainstream U.S. market principally as an anti-anxiety
      preparation. The effects of the long-term consumption of kava have not been
      documented adequately. Preliminary studies suggest possible serious organ system
      effects. The potential carcinogenicity of kava and its principal constituents are
      unknown. As such, kava extract was nominated for the chronic tumorigenicity
      bioassay conducted by the National Toxicology Program (NTP). At present
      toxicological evaluation of kava extract is being conducted by the NTP. The
      present review focuses on the recent findings on kava toxicity and the mechanisms
      by which kava induces hepatotoxicity.

PMID- 18322869
TI  - What does respirator certification tell us about filtration of ultrafine
      particles?
AB  - Recent interest in exposures to ultrafine particles (less than 100 nm) in both
      environmental and occupational settings led the authors to question whether the
      protocols used to certify respirator filters provide adequate attention to
      ultrafine aerosols. The authors reviewed the particle size distribution of
      challenge aerosols and evaluated the aerosol measurement method currently
      employed in the National Institute for Occupational Safety and Health (NIOSH)
      particulate respirator certification protocol for its ability to measure the
      contribution of ultrafine particles to filter penetration. Also considered were
      the differences between mechanical and electrically charged (electret) filters in
      light of the most penetrating particle size. It was found that the sodium
      chloride (NaCl) and dioctylphthalate (DOP) aerosols currently used in respirator
      certification tests contain a significant fraction of particles in the ultrafine
      region. However, the photometric method deployed in the certification test is not
      capable of adequately measuring light scatter of particles below approximately
      100 nm in diameter. Specifically, 68% (by count) and 8% (by mass) of the
      challenge NaCl aerosol particles and 10% (by count) and 0.3% (by mass) of the DOP
      particles below 100 nm do not significantly contribute to the filter penetration
      measurement. In addition, the most penetrating particle size for electret filters
      likely occurs at 100 nm or less under test conditions similar to those used in
      filter certification. The authors conclude, therefore, that the existing NIOSH
      certification protocol may not represent a worst-case assessment for electret
      filters because it has limited ability to determine the contribution of ultrafine
      aerosols, which include the most penetrating particle size for electret filters.
      Possible strategies to assess ultrafine particle penetration in the certification
      protocol are discussed.

PMID- 18322870
TI  - Exposure to wood dust, resin acids, and volatile organic compounds during
      production of wood pellets.
AB  - The main aim of this study was to investigate exposure to airborne substances
      that are potentially harmful to health during the production of wood pellets,
      including wood dust, monoterpenes, and resin acids, and as an indicator of diesel
      exhaust nitrogen dioxide. In addition, area measurements were taken to assess
      background exposure levels of these substances, volatile organic compounds
      (VOCs), and carbon monoxide. Measurements were taken at four wood pellet
      production plants from May 2004 to April 2005. Forty-four workers participated in
      the study, and a total of 68 personal measurements were taken to determine
      personal exposure to wood dust (inhalable and total dust), resin acids,
      monoterpenes, and nitrogen dioxide. In addition, 42 measurements of nitrogen
      dioxide and 71 measurements of total dust, resin acids, monoterpenes, VOCs, and
      carbon monoxide were taken to quantify their indoor area concentrations. Personal
      exposure levels to wood dust were high, and a third of the measured levels of
      inhalable dust exceeded the Swedish occupational exposure limit (OEL) of 2 mg/m3.
      Parallel measurements of inhalable and total dust indicated that the former were,
      on average, 3.2 times higher than the latter. The data indicate that workers at
      the plants are exposed to significant amounts of the resin acid 7
      oxodehydroabietic acid in the air, an observation that has not been recorded
      previously at wood processing and handling plants. The study also found evidence
      of exposure to dehydroabietic acid, and exposure levels for resin acids
      approached 74% of the British OEL for colophony, set at 50 microg/m3. Personal
      exposure levels to monoterpenes and nitrogen dioxide were low. Area sampling
      measurements indicated that aldehydes and terpenes were the most abundant VOCs,
      suggesting that measuring personal exposure to aldehydes might be of interest.
      Carbon monoxide levels were under the detection limit in all area measurements.
      High wood dust exposure levels are likely to have implications for worker health;
      therefore, it is important to reduce exposure to wood dust in this industry.

PMID- 18322871
TI  - Endoscopic full-thickness plication (Plicator) with two serially placed implants
      improves esophagitis and reduces PPI use and esophageal acid exposure.
AB  - BACKGROUND AND STUDY AIMS: Recently, several endoluminal procedures for the
      treatment of gastroesophageal reflux disease (GERD) have been introduced. Most of
      these techniques have been abandoned because they lack long-term efficacy or have
      serious side effects. In a recently published prospective randomized, sham
      controlled trial, the Plicator was shown to be effective at controlling reflux
      symptoms and esophageal acid exposure. In all previous studies, only a single
      implant was used. The aim of the present pilot study was to determine the safety
      and efficacy of two serially placed Plicator implants. PATIENTS AND METHODS:
      Thirty-seven patients requiring maintenance therapy with proton pump inhibitors
      (PPIs) were enrolled in this single-center pilot study. All patients received two
      Plicator implants. Exclusion criteria were hiatus hernia larger than 3 cm, grade
      IV esophagitis, Barrett's esophagus, and esophageal motility disorders. The
      primary study end point was at least 50 % improvement in the GERD Health-Related
      Quality of Life (HRQL) score. Secondary end points included GERD medication use,
      esophageal acid exposure, esophagitis grade, and heartburn/regurgitation scores.
      RESULTS: Thirty-seven patients underwent endoscopic full-thickness plication
      using two serially placed Plicator implants. At 6 months after treatment, the
      proportion of patients achieving at least 50 % improvement in GERD-HRQL score was
      68 %. Complete cessation of PPI treatment was achieved in 59 % of patients. In pH
      studies conducted at 6 months (n = 29), median percentage of time for which pH
      was below 4 decreased by 36 %, with 28 % of patients experiencing pH
      normalization. There were no serious adverse events requiring intervention.
      CONCLUSIONS: Endoscopic full-thickness plication using two serially placed
      Plicator implants was both safe and effective in reducing esophagitis, GERD
      symptoms, medication use, and esophageal acid exposure.

PMID- 18322872
TI  - Routine coagulation of visible vessels may prevent delayed bleeding after
      endoscopic submucosal dissection--an analysis of risk factors.
AB  - BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) has been
      reported to be associated with a higher complication rate than standard
      endoscopic mucosal resection. We aimed to clarify the risk factors for delayed
      bleeding after ESD for early gastric cancer (EGC). METHODS: 1083 EGCs in 968
      consecutive patients undergoing ESD during a 4-year period were reviewed. Post
      ESD coagulation (PEC) preventive therapy of visible vessels in the resection
      area, using a coagulation forceps, was introduced and mostly performed during the
      later 2 years. Various factors related to patients, tumors, and treatment
      including PEC were investigated using univariate and multivariate analysis with
      regard to delayed post-ESD bleeding, evidenced by hematemesis or melena, that
      required endoscopic treatment. RESULTS: Delayed bleeding occurred after ESD of 63
      lesions (5.8 % of all lesions and 6.5 % of patients), controlled in all cases by
      endoscopic hemostasis; blood transfusion was required in only one case. Tumor
      location in the upper third of the stomach and PEC were independent factors
      indicating a lower rate of delayed bleeding according to both univariate and
      multivariate analysis. CONCLUSIONS: This retrospective study suggested that
      preventive coagulation of visible vessels in the resection area after ESD may
      lead to a lower bleeding rate.

PMID- 18322874
TI  - Destroy the bleeding vessels and spare the ischemic mucosa.

PMID- 18322873
TI  - Early closure of a multicenter randomized clinical trial of endoscopic stenting
      versus surgery for stage IV left-sided colorectal cancer.
AB  - BACKGROUND AND STUDY AIMS: The introduction of self-expandable metal stents has
      offered a promising alternative for palliation of malignant left-sided colonic
      obstruction. This randomized clinical trial aimed to assess whether a nonsurgical
      policy, with endoluminal stenting, is superior to surgical treatment in patients
      with stage IV left-sided colorectal cancer and imminent obstruction. PATIENTS AND
      METHODS: Patients with incurable left-sided colorectal cancer who fulfilled the
      study criteria were randomly assigned to nonsurgical or surgical treatment. The
      primary outcome measure was survival in good health out of hospital (World Health
      Organization performance scores 0 or 1). RESULTS: A high number of serious
      adverse events in the nonsurgical arm led to premature closure of the trial. Ten
      patients were allocated to surgical treatment and 11 patients to nonsurgical
      palliation. The median survival in good health out of hospital during the first
      year was 56 days (interquartile range 7.5 - 338.5 days) in the surgical arm vs.
      38 days (interquartile range 5.25 - 288.75 days) in the nonsurgical arm (P =
      0.68). Eleven adverse events (six perforations) occurred in the nonsurgical arm
      vs. one adverse event in the surgical arm (P < 0.001). Of the six perforations,
      two were stent-related because they occurred at the proximal edge of the stent by
      erosion through a normal colon wall; one was probably stent-related (it was
      located in the region of the proximal half of the stent); one was a colon
      blowout; and two were late tumor perforations in patients on chemotherapy.
      CONCLUSIONS: The unexpected high rate of perforation in the nonsurgical arm might
      be specifically WallFlex-related or enteral stent-related in patients on
      chemotherapy and warrants attention.

PMID- 18322875
TI  - Endoscopic ultrasound visibility of celiac ganglia.

PMID- 18322877
TI  - What induces colitis? Hydrogen peroxide or peracetic acid.

PMID- 18322880
TI  - NAT1 genotypes do not predict response to mesalamine in patients with ulcerative
      colitis.
AB  - BACKGROUND: 5- Aminosalicylic acid (5-ASA) is metabolised in colonic mucosa by N
      acetyltransferase 1 (NAT1). Common genetic polymorphisms in this enzyme result in
      rapid or slow acetylation. 5-ASA treatment causes side effects in up to 10 % of
      patients with ulcerative colitis (UC). We therefore determined genetic variations
      of NAT1 in patients with UC and looked for a possible association with the
      clinical response to 5-ASA. METHODS: DNA was obtained from 78 patients with UC.
      77 % of the patients were in remission during 5-ASA treatment, whereas 23 %
      suffered from active disease. NAT1 genotyping was performed for 23 known alleles
      using RFLP and sequence analysis. Clinical response to 5-ASA was determined by
      medical record review and associated with NAT1 genotypes. RESULTS: Utilising PCR
      we amplified a 570-bp coding region of the human NAT1 gene in addition to 240 bp
      in the 3'-untranslated region (UTR). 4 NAT1 alleles previously known as NAT1*3,
      *4, *10 and *11 were recovered. 31 % of the patients were heterozygous and 4 %
      homozygous for the NAT1*10 allele. 6 % were heterozygous for the NAT1*3 allele. 6
      % were heterozygous for the NAT1*11 allele. No association was found between NAT1
      genotype and clinical response as well as side effects to 5-ASA in patients with
      UC. CONCLUSIONS: NAT1 genotypes do not predict response or side effects to
      mesalamine in patients with UC. Variations caused by non-genomic effects may be
      associated with the clinical response to 5-ASA.

PMID- 18322881
TI  - [Complications in double-balloon-enteroscopy: results of the German DBE
      register].
AB  - INTRODUCTION: The introduction of double-balloon enteroscopy for the
      investigation of the small bowel in 2001 was a milestone in GI endoscopy because
      it allows us to carry out therapeutic interventions as well as diagnostic
      procedures in the small bowel. Because interventional procedures in endoscopy
      increase the risk of complications, e.g., in colonoscopy and only limited data
      were reported regarding the risk of DBE, we introduced a double-balloon
      enteroscopy register (DBE Register) in Germany. AIM AND METHODS: The purpose of
      this study was to evaluate the complication rate of DBE in a larger group of
      patients. We contacted all endoscopic units using DBE in Germany in January 2006
      and asked for their participation in the register, the examination data and their
      present complications beginning in January 2003 until 15.07.2006 using a
      questionnaire. RESULTS: The participation rate of 85 endoscopic centres using the
      DBE technique was 75 % (64 centres). They reported 3894 DBE examinations (2685
      using the oral route, 1209 using the anal route) with 1086 interventions. 48
      complications were reported (1.2 %). Acute pancreatitis occurred in 9 patients
      with 1 lethal course of disease, all of them receiving a DBE using the oral
      route. Thus, the pancreatitis rate after oral DBE was 0.34 %. Perforation
      happened in 8 cases, all of them needed surgery. One patient died during the
      course of the disease. 6 perforations occurred after polypectomy, so the
      perforation rate after polypectomy during DBE is 3.4 % in this study. In 6 cases
      major bleeding was reported, 4 in the context of polypectomy and 2 after biopsy.
      All patients received endoscopic treatment and recovered from this complication.
      CONCLUSION: DBE is in this by now largest collection of cases a safe endoscopic
      procedure with an overall complication rate of approximately 1%. For diagnostic
      DBE pancreatitis is the most frequent complication and has to be taken in
      consideration in the written informed consent.

PMID- 18322882
TI  - Treatment of massive cecal bleeding in a 28-Year-old patient with homozygous
      factor V deficiency with activated factor VII.
AB  - Factor V deficiency is usually accompanied with recurrent epistaxis, menorrhagia
      and haemorrhages after trauma. So far, gastrointestinal bleeding has not been
      reported. We describe here the first case of severe cecal bleeding in a 28-year
      old woman with homozygous factor V deficiency. As a reasonable alternative to
      large amounts of fresh frozen plasma, we indicated recombinant activated factor
      VII (rFVIIa), as supra-physiological concentrations directly activate factor X
      and prothrombin on the surface of activated platelets. With this regimen, the
      bleeding immediately stopped and the patient was discharged three days later.
      Rotation thromboelastometry studies showed a marked improvement in clot
      generation after rFVIIa infusion. We conclude that massive cecal mucosal bleeding
      is a possible manifestation of homozygous factor V deficiency and rFVIIa could be
      a successful therapy.

PMID- 18322883
TI  - Severe paraneoplastic gastroparesis associated with anti-Hu antibodies preceding
      the manifestation of small-cell lung cancer.
AB  - Gastroparesis is a common but challenging disorder which can be idiopathic or
      induced by a variety of underlying diseases, most frequently by diabetes, or post
      surgical conditions of the upper abdomen. Clinicians must also consider rare
      causes of gastric motor dysfunction, such as collagen vascular disorders and
      paraneoplastic syndromes. Here we present the case of a patient with severe
      gastroparesis, who was admitted to our hospital for vomiting and weight loss of
      25 kg within four months. Endoscopy showed a dilated fluid-filled stomach without
      peristalsis but no obstruction. High titres of anti-Hu antibodies were detected
      in patient's serum, supporting the diagnosis of severe paraneoplastic
      gastroparesis with chronic intestinal pseudo-obstruction. Fine-needle aspiration
      of suspicious mediastinal lymph nodes guided by endoscopic ultrasound revealed
      lymphatic metastases of a small-cell lung carcinoma. Jejunal tube feeding and
      chemotherapy with carboplatin and etoposide were initiated. Paraneoplastic
      gastrointestinal dysmotility is rare, however, clinicians should consider this
      differential diagnosis in otherwise unexplained gastrointestinal motor
      dysfunction. The pathophysiology of paraneoplastic gastroparesis, the diagnostic
      relevance of anti-Hu antibodies as well as therapeutic options are discussed.

PMID- 18322884
TI  - [Nutritional factors and nutritional therapy for irritable bowel syndrome--what
      is worthwhile?].
AB  - The prevalence of irritable bowel syndrome (IBS) has increased over the last 50
      years in countries where a Western-style diet has been prominent or introduced
      and 20 - 65 % of patients with irritable bowel syndrome (IBS) attribute their
      symptoms to something in food that activates an abnormal response. However, data
      from dietary elimination and re-challenge studies are inconclusive. Although
      investigations have shown that bran may be helpful in some patients, a complete
      review of the literature does not reveal conclusive evidence that a high fibre
      diet therapy is effective in IBS. From the limited reports on probiotics, there
      appears to be a trend to decreasing symptoms. Despite numerous reviews on this
      subject, it is very difficult to give general dietary advice to IBS patients, but
      dietary experts may have a positive role in managing such patients. It is clear
      that much more prospective research is needed to study both dietary factors and
      probiotics in these areas.

PMID- 18322885
TI  - [Incidentaloma of the pancreas].
AB  - The term incidentaloma refers to an asymptomatic mass detected accidentally
      during a technical examination, mostly by radiological methods, when performed in
      a patient examined for other conditions or situations. Surgery is the adequate
      therapy for adrenal incidentalomas with increasing size, a size bigger than 4 cm
      at detection, hormone-activity or malignant histology. Incidentalomas of the
      adrenal and thyroid gland are still often dismissed because they are common and
      mostly benign. Incidentalomas of the pancreas are distinct and less frequent. At
      present, no evidence-based guidelines exist for the management of asymptomatic
      pancreatic lesions. Only few clinical studies describe pancreatic incidentalomas,
      however these studies claim a malignant histology of up to 30 % and of up to 50 %
      for pre-malignant incidentalomas of the pancreas. Thus, we recommend an early
      resection of pancreatic incidentalomas with a size of > 2 cm, in younger patients
      without concomitant diseases or increased operative risk, with a malignant
      histology, and with mucinous cells and increased tumour markers in blood samples.
      Organ-saving procedures or radical pancreatectomy are possible while both methods
      are safe and have a very low complication risk. The surgical resection of
      pancreatic incidentalomas offers a significant advantage in survival when the
      total collective of affected individuals is taken into account.

PMID- 18322888
TI  - [From the expert's office: mandibula cyst formation after septorhinoplasty:
      medical fault?].

PMID- 18322889
TI  - [The Merkel cell carcinoma].
AB  - The Merkel cell carcinoma is a rare tumor of the subdermal tissue. Its origin are
      Merkel cells or the subcutaneous pluripotential stem cells. The etiology of the
      tumor is unknown, however, exposition to UV radiation and immunosuppression are
      relevant predisposing factors. Clinically, a subcutaneous rapidly growing tumor
      with or without enlarged lymph nodes is seen. Beside excisional biopsy and
      various imaging modalities, somatostatin-receptor-scintigraphy plays an important
      role in diagnostic. Surgical resection of the tumor combined with neck dissection
      followed by radiation therapy is the current therapy of choice. Different
      chemotherapy protocols are available for patients with distant metastasis.

PMID- 18322890
TI  - [Important News for HaMiPla].

PMID- 18322891
TI  - [The hand--handless--prostheses].

PMID- 18322892
TI  - [The hands--means of expression for relationship, creativity and coping].
AB  - The hand is an important active sense organ. Hands help human beings to organise
      and change the environment, and most developments of mankind would not have been
      possible without hands. The hands also made a great contribution to the high
      degree of brain development. The hands are an important characteristic feature of
      identity and identification and sign of individuality as well. Human hands have a
      long history as an instrument of social interaction and as an object of social
      attention. The language of hands offers many kinds of expression and gestures
      help to underline the words.

PMID- 18322893
TI  - [Peromelia].
AB  - Peromelia is a rare but mutilating congenital deformity representing failure of
      formation of parts of the upper limb. The deformity is presented unilaterally in
      the vast majority of the cases. Usually, these children are totally healthy
      beside from the deformity and are not seriously handicapped by the deformity.
      Correction of the deformity by hand- or forearm transplantation is not yet
      possible. Treatment consists of support with prosthesis in case of missing upper-
      or forearm and construction of fingers by toe-to-hand transplantation in case of
      missing fingers and hand. Treatment is not mandatory as the children use the
      stump in combination with their unimpaired upper limb for bimanual daily life
      activities. The mutilating aspect of the deformity frequently does impair
      especially parents but also the children to a higher extent than the actual
      functional disability. Psychological aid is recommended to support children and
      parents in managing their life with this severe deformity.

PMID- 18322894
TI  - [Upper-extremity amputation in tumours of the shoulder and upper arm--experiences
      of the Vienna Bone Tumour Registry].
AB  - Malignant lesions of the bones and soft tissues require radical or wide resection
      to achieve adequate therapy. Due to the many developments in terms of adjuvant
      modalities, diagnostics and surgical expertise today there are several modes of
      therapy as alternatives to amputation in the treatment of malignant tumours of
      the shoulder and upper arm. After resection of smaller tumours excellent
      functional results can be obtained by the use of modular endoprostheses, whereas
      large neoplasms adjacent to the neurovascular bundle require resection
      replantation to allow salvage of the hand. Within the Vienna Bone Tumour
      Registry, 100 patients out of a total of more than 6500 have been treated for
      such lesions: 62 received an endoprostheses, 18 resection-replantation and 20
      amputation. In cases of primary malignant tumours the incidence of lung
      metastases was higher in the resection-replantation group (50 %) and amputation
      group (42 %) than in the prostheses group (11 %), which has been linked to larger
      tumour size in the former two groups. Radical or wide resections were obtained in
      95 % of the prostheses group, as compared to 75 % and 78 % in the amputation
      group and the resection-replantation group, respectively, due to invasion into
      the neurovascular bundle. Over time the number of amputations decreased
      simultaneously with the increase of endoprostheses whereas the number of
      resection-replantations remained equal at our institution. Amputation today still
      plays a crucial role in the treatment of intralesionally resected tumours, as
      surgical contamination can make limb salvage impossible. Therefore, the
      importance of biopsy in the therapeutical algorithm of bone and soft tissue
      tumours has to be emphasised again.

PMID- 18322895
TI  - [Evaluation of macroamputations of the upper extremity in the management of
      primary malignant bone and soft-tissue tumours using the DASH score].
AB  - PURPOSE/BACKGROUND: The purpose of this retrospective analysis was to identify
      patients with macroamputations of the upper extremity due to malignant bone or
      soft-tissue tumours at a single institution. The German DASH score (Disability of
      Arm, Shoulder, Hand) was obtained in order to measure how patients manage their
      daily activities. PATIENTS AND METHODS: Between 1998 and 2005, 1652 patients were
      operated due to a bone or soft-tissue tumour, 370 of these due to a malignant one
      (22 %). The tumour was localised in the lower extremity or in the pelvis in 246
      cases, in the trunk in 38 and in the upper extremity in 86 cases. These 86
      primary malignant tumours comprised 22 bone and 64 soft tissue tumours.
      Amputations had to be performed in the lower extremity in 14 % (35/246) and in
      the upper extremity in 7 % (6/86). Six patients with macroamputations of the
      upper extremity were identified and in five of these the DASH score was obtained.
      RESULTS: The mean DASH score for the module 1 (disability/symptom) was 75.1
      points ([sum of responses - 30]/1.2), for module 2 (work) 92.4 ([sum of responses
      - 4]/0.16), and for module 3 (sports/performing arts) 90 points ([sum of
      responses - 4]/0.16). Only two patients worked again and only one played an
      instrument. CONCLUSION: Despite neo-/adjuvant therapeutic options and modified
      reconstructive procedures 7 % of patients with malignant bone or soft tissue
      tumours of the upper extremity had to undergo an amputation. The DASH score is an
      appropriate instrument to measure the disability after upper limb amputation due
      to tumour.

PMID- 18322896
TI  - [About the self-reported quality of life after amputation of the hand in patients
      with upper extremity tumors].
AB  - PURPOSE/BACKGROUND: Amputation proximal to the wrist may be oncologically
      dictated in cases of upper extremity soft tissue sarcoma and aggressive
      fibromatosis. Literature on functional long-term results and patient-oriented
      assessment is sparse. Our study is concerned with subjective impressions of
      quality of life and upper extremity health status and their importance in the
      evaluation and interpretation of results after amputation of the hand.
      PATIENTS/METHODS: Between 1999 and 2007, 14 patients (6 females/8 males; average
      age: 25 years) were operated because of a soft tissue sarcoma (n = 11) or
      aggressive fibromatosis (n = 3). Ten patients underwent limb-sparing surgery.
      There were two amputations at the level of the forearm. Local recurrence
      following forequarter amputation due to aggressive fibromatosis required
      reoperation in another patient. A heterotopic replantation after resection was
      carried out in one patient. In patients with amputations, the self-reported upper
      extremity-specific health status and quality of life were measured with the DASH
      score. Disturbances in body image and symptoms of depression were assessed
      psychiatrically. RESULTS: In two cases with amputations, minimal impairments in
      everyday life and a high reported quality of life were observed (DASH scores:
      3,5). CONCLUSION: Self-reported upper extremity health status and quality of life
      following amputation of the hand can be in contrast to the objective pathology.
      In patient-oriented assessment of results, individual psychosocial factors that
      may affect results must be taken into consideration. They also must not be
      neglected when determining whether patients are suitable candidates for
      prosthetic devices.

PMID- 18322897
TI  - [Subjective impairment after macroamputation of the upper extremity].
AB  - BACKGROUND: The subjective outcome following macroamputation of the upper limb
      was evaluated using the DASH score. PATIENTS AND METHODS: In a retrospective
      study, 11 patients with stumps of the upper limb following trauma were
      investigated 5.6 years after injury. Data according to injury pattern, age,
      gender, level of amputation and DASH score were collected. RESULTS: Included are
      2 unilateral and 3 bilateral forearm amputees and 6 patients with upper arm
      amputation. Only males were seen with a mean age of 32 years. Amputation occurred
      following polytrauma in 3 cases while in the other 8 cases the amputated limb was
      unreconstructably mangled. 8 patients wear a prosthesis. 4 (36 %) patients are
      unemployed. The mean DASH score was 44.8, in bilateral forearm amputees 74.16, in
      unilateral upper-arm amputees 38.47 and in unilateral lower forearm amputees
      43.33. Patients with bilateral amputation showed the greatest functional and
      social impairment. Mean pain was 40 % of the pain section in the DASH
      questionnaire and showed no difference with regard to the level of amputation or
      bilateral injury. All patients are socially integrated. Patients with unilateral
      amputation rated psychological impairment higher than functional impairment.
      CONCLUSION: Patients with macroamputation of the upper extremity show high
      psychological and functional impairment. Pain, deficits in function and still not
      optimal prosthetic devices result in a high percentage of unemployment.

PMID- 18322898
TI  - [Replantation or prosthesis: individual planning].
AB  - Rehabilitation of a replanted upper limb is difficult and has to start close to
      the operation. Physical and occupational therapy are working close together. The
      unimpaired opposite upper extremity must be trained as well. Replantation of
      upper limb causes not only a lot of reoperations with extended morbidity, but
      also problems in social, family and psychic. After eventual amputation of the
      upper limb prosthetic compensation is necessary as soon as possible. There is a
      gap open between the technical and financial possibilities. To avoid spine
      disorders a shoulder cap is necessary if prosthetic compensation is not possible
      in higher amputations.

PMID- 18322899
TI  - [Exoskeletal prosthetic treatment following congenital or acquired defects of the
      upper extremities].
AB  - The exoskeletal prosthetic care of the upper extremities poses a variety of
      challenges to the experienced orthopaedic technician. In addition to the clinical
      factors which are initially decisive, such as general condition, amputation
      level, condition of the stump and resilience, the patient must be given equal
      attention when it comes to the design of the prosthetic device. The requirement
      to regain physical appearance which, in most cases, approaches the same
      importance as retrieving the best possible motor skills, underscores the
      necessary variety in design options for the prosthetic device. The following
      article intends to demonstrate diverse options in orthopaedic care for the upper
      extremities. On the basis of various care examples, the requirements and
      individual approaches in exoskeletal prosthetic care of the upper extremities
      will be illustrated.

PMID- 18322900
TI  - [Selective nerve transfers to improve the control of myoelectrical arm
      prostheses].
AB  - To date, the movement of myoelectrical arm prostheses proceeds via two
      transcutaneous electrodes that are controlled by two separately innervated muscle
      groups. The various control levels are chosen by co-contractions of these muscles
      and the respective level is linearly controlled by the same muscles. A harmonious
      course of movement as in the corresponding natural pattern of motion is not
      possible in this way. An appreciable improvement would be given by the control of
      the individual movement levels by signals that correspond neuronally with the
      natural pattern of motion. Just recently, prostheses with six control levels have
      been realised technically. The objective is to separate the major arm nerves,
      such as the musculocutaneous nerve, radial nerve, median nerve and ulnar nerve,
      from the proximal arm nerve plexus and to transfer them to the residual nerve
      branches of muscles near the stem in order to create meaningful neuromuscular
      units that can serve as impulse sources for myoelectrical prosthesis. As target
      muscles, above all, one can consider the major/minor pectoral muscles or,
      respectively, the latissimus muscle. According to the activity of the donor
      nerves, these muscles would contract and control the prosthesis via
      transcutaneous electrode. In this way, a harmonious control corresponding
      intuitively to the natural pattern of movement would be possible without the
      necessity for the patient to continuously switch between the various control
      levels. Prerequisites for this are intact proximal muscle groups and a more or
      less intact arm nerve plexus with the possibility to isolate donor nerves
      according to the topographic-anatomic situation. For this reason, a preoperative
      MRI examination, a high resolution sonographic study and balancing NLG and EMG of
      the residual nerve plexus are necessary. For the preoperative planning phase as
      well as for the postoperative follow-up, a detailed procedure has been
      established, in cooperation with the innovation department of the Otto Bock
      company, to create the most meaningful switch levels, to optimise electrode
      placement as well as to clarify prosthesis incorporation. Finally, a complex
      rehabilitation programme is necessary for the patient to achieve an optimal
      result.

PMID- 18322901
TI  - [ARMOR: an electromechanical robot for upper limb training following stroke. A
      prospective randomised controlled pilot study].
AB  - PURPOSE: Due to the complexity of the upper motor neuron syndrome, functional
      improvement in the paretic upper limb after stroke continues to be a challenge in
      neurorehabilitation. Robot-assisted training has been shown to be useful in
      relearning gait. In order to achieve similar results in the upper limb, an
      electromechanical arm robot (ARMOR), capable of moving all joints through complex
      patterns, has been developed. MATERIAL AND METHOD: Eight patients following
      stroke of different etiologies were included in a clinical AB-BA cross-over study
      comparing ARMOR training with EMG-triggered neuromuscular electrical stimulation
      (EMG-NMES). Chedoke-McMaster Stroke Assessment, modified Ashworth Scale,
      goniometry (Neutral-0-Method), dynamometry and Functional Dexterity Test served
      as outcome measures. RESULTS: ARMOR training resulted in more improvement of
      muscle tone (p = 0.004), range of movement (ROM) (p = 0.005) and dexterity, but
      less improvement of strength, than EMG-NMES. Chedoke-McMaster Stroke Assessment
      showed improvement of at least one point in shoulder pain and arm and hand
      activity during ARMOR training, while these values did not change with EMG-NMS.
      Better results of ARMOR training were achieved in the earlier phase (A1) than in
      the later phase (A2). CONCLUSION: This study demonstrates the positive effect of
      automatised training with a new electromechanical arm robot (ARMOR), and
      documents its clinical applicability in the rehabilitation of the paretic upper
      extremity in stroke patients.

PMID- 18322902
TI  - Spirituality as a core domain in the assessment of quality of life in oncology.
AB  - OBJECTIVES: This study investigated including spiritual wellbeing as a core
      domain in the assessment of quality of life (QOL) in an Australian oncology
      population. METHODS: Four hundred and ninety consecutive cancer patients with
      mixed diagnoses completed the Functional Assessment of Chronic Illness Therapy-
      Spiritual Well-Being (FACIT-Sp) and the Mental Adjustment to Cancer (MAC) scale.
      RESULTS: Overall, 449 patients completed assessments. Spiritual wellbeing
      demonstrated a significant, positive association with QOL (r=0.59), fighting
      spirit (r=0.49) and a significant, negative relationship with
      helplessness/hopelessness (r=-0.47) and anxious preoccupation (r=-0.26). A
      hierarchical multiple regression showed spiritual wellbeing to be a significant,
      unique contributor to QOL beyond the core domains of physical, social/family, and
      emotional wellbeing (R(2) change=0.08, p=0.000). However, high levels of
      meaning/peace or faith did not appear to significantly impact patients' ability
      to enjoy life despite chronic symptoms of pain or fatigue, making the current
      results inconsistent with other findings. CONCLUSION: Results lend further
      support to the biopsychosocialspiritual model. By failing to assess spiritual
      wellbeing, the 'true' burden of cancer is likely to be miscalculated. However, at
      this stage, the exact clinical utility of spirituality assessment is unclear.

PMID- 18322903
TI  - Assessing the effect of beauty treatments on psychological distress, body image,
      and coping: a longitudinal study of patients undergoing surgical procedures for
      breast cancer.
AB  - INTRODUCTION: Women with breast cancer may have significant problems adjusting to
      disease and therapy due to their association with significant changes in body
      image and sexuality. The aim of this study was to evaluate the effect of beauty
      treatments in combination with routine cancer care. METHODS: One hundred women
      with breast cancer were randomly assigned to a group receiving beauty treatments
      during hospitalization or a control group. Psychological distress, body image and
      coping were assessed twice during the hospitalization period: the day before
      surgery (baseline) and 6 days later (Time 1). A follow-up assessment was
      performed three months later (Time 2). RESULTS: Three months after surgery,
      patients who had received beauty treatments reported higher body-image scores
      than the control group, but there was no effect in psychological distress.
      Helplessness/hopelessness increased over time in the control group but not in the
      group receiving beauty treatments. CONCLUSION: Overall, this study provides
      evidence of the usefulness of beauty treatments for breast-cancer patients, in
      combination with routine care. Although these treatments did not seem to
      alleviate psychological distress directly, they had a beneficial impact on body
      image and may strengthen patients' social support and self-esteem.

PMID- 18322904
TI  - Prenatal sonographic features of isolated cleft soft palate with anterior axial
      three-dimensional view reconstruction.

PMID- 18322905
TI  - Evaluating drug toxicity signals: is a hierarchical classification of evidence
      useful or a hindrance?
AB  - PURPOSE: Only randomized clinical trials (RCTs) are deemed suitable to determine
      causality, as epidemiological studies are considered not 'robust'. The objective
      of this study was to evaluate whether causality should remain the only
      consideration with drug toxicity signals. Cyclooxygenase-2 (Cox-2) inhibitors
      provided an example. METHODS: Our study population included patients aged 40+
      years prescribed Cox-2 inhibitors in the General Practice Research Database
      (GPRD) (N = 150 000). We estimated the risks of upper gastrointestinal (GI)
      events and myocardial infarction (MI). Attributable risks were estimated using
      simulation methodology based on various hypothetical scenarios. RESULTS: The risk
      benefit profile was strongly related to the rate of GI events. With a RCT
      incidence, the GI benefits would exceed MI risks. With a 'real-life' GI
      incidence, the benefits did not exceed the risks substantially. The onset and
      offset of drug effects also predicted the magnitude of both risks and benefits.
      If risks and benefits occurred in different sub-groups, the risk-benefit profile
      varied substantially. Also, it was found that any restriction of use to patients
      at high risk of drug toxicity may not improve the risk-benefit profile when this
      restriction affected patients who would benefit most. CONCLUSIONS: We conclude
      that rigid classification of evidence is not appropriate in the monitoring of
      risks and benefits and all valid study evidence--not only that derived from a RCT
      -needs to be included. The first priority should be to consider the potential
      impact of a drug toxicity signal.

PMID- 18322906
TI  - Antimicrobial prescribing trends in primary care: implications for health policy
      in Bahrain.
AB  - PURPOSE: To evaluate antimicrobial prescribing pattern by primary care
      physicians. METHODS: A nation-wide, retrospective, multi-centric prescription
      audit was carried out in primary care health centres in Bahrain. RESULTS:
      Systemic antimicrobials ranked the fourth most common class of drugs prescribed.
      Amoxycillin, cephalexin, erythromycin, ciprofloxacin and cotrimoxazole were
      prescribed by general practitioners (GPs) more often than by family physicians
      (FPs) (p < 0.05). With respect to prescribing of other antimicrobials and
      anthelmintic mebendazole, the differences between GPs and FPs were
      nonsignificant. Seventy-seven per cent of systemic antimicrobials prescribed were
      for respiratory tract infections (RTIs). Topical antimicrobial preparations for
      ear and eye infections were prescribed by GPs in a rate significantly higher than
      by FPs (p < 0.05); of these, chloramphenicol and Locacorten vioform (flumethasone
      + clioquinol) ear drops and sulphacetamide eye drops were more often prescribed
      by GPs (p < 0.05). There were no significant differences in prescribing between
      GPs and FPs as regards topical antimicrobials used for oropharyngeal, skin and
      vulvovaginal infections. CONCLUSION: Antimicrobials were extensively used in
      primary care, mainly for treating RTIs. The general practitioners were more avid
      prescribers of antimicrobials compared to the FPs. Rational use of antimicrobials
      in primary care should be encouraged and the reasons for the observed differences
      in prescribing of antimicrobials between the GPs and FPs need further evaluation.

PMID- 18322907
TI  - Assessment of the severity of dementia: validity and reliability of the Chinese
      (Cantonese) version of the Hierarchic Dementia Scale (CV-HDS).
AB  - BACKGROUND: With the rapid growth of the older population, early detection of
      cognitive deficits is crucial in slowing down functional deterioration of the
      elderly persons. OBJECTIVES: To examine the validity and reliability of the
      Chinese (Cantonese) version of the Hierarchic Dementia Scale (CV-HDS) for Chinese
      older persons in Hong Kong. METHODS: The HDS was translated into Cantonese
      Chinese. The content and cultural validity were evaluated by six expert panel
      members. Sixty-two participants with diagnosis of dementia were recruited for
      evaluation. Inter-rater reliability, test-retest reliability, internal
      consistency and concurrent validity were examined. RESULTS: The CV-HDS
      demonstrated satisfactory psychometric properties. inter-rater reliability and
      test-retest reliability were high (alpha=0.89 and alpha=0.94 respectively). High
      value of Cronbach's alpha (alpha=0.94) demonstrated good internal consistency.
      The concurrent validity of CV-HDS, through correlation with its scores with that
      of the Chinese version of Mini Mental Status Examination, was established (ranged
      from r=0.58 to r=0.78, p<0.01). CONCLUSIONS: The CV-HDS is a reliable and valid
      instrument for assessing severity of cognitive impairment in Cantonese speaking
      Chinese people with dementia. It facilitates treatment planning to optimize the
      effects of functional training and rehabilitation.

PMID- 18322908
TI  - Immobilization of penicillin G acylase on poly[(glycidyl methacrylate)-co
      (glycerol monomethacrylate)]-grafted magnetic microspheres.
AB  - Poly[(glycidyl methacrylate)-co-(glycerol monomethacrylate)]-grafted magnetic
      microspheres were prepared by graft random copolymerization via ATRP from polymer
      microspheres with dispersed Fe(3)O(4) nanoparticles. Penicillin G acylase (PGA)
      was immobilized onto the polymer brush-grafted magnetic microspheres. The
      immobilized PGA prepared with initial glycidyl methacrylate/glycerol
      monomethacrylate ratios of 40/60 to 60/40 possessed higher catalytic activity
      than that prepared with higher proportions of glycidyl methacrylate in the
      initial monomer mixture. The immobilized PGA showed high thermal stability and
      enhanced tolerability to the pH variance.

PMID- 18322909
TI  - Lipase-catalyzed ring-opening polymerization of molecularly pure cyclic oligomers
      for use in synthesis and chemical recycling of aliphatic polyesters.
AB  - The lipase-catalyzed ROP of molecularly pure cyclic oligomers with a definite
      degree of oligomerization is analyzed with respect to the molecular weights of
      the resulting polymers and certain kinetic parameters of the enzymatic reaction.
      Cyclic BA dimers, trimers, and tetramers polymerize faster than the equivalent
      monomer; however, the latter produces PBA of significantly higher molecular
      weight. The reason is that the ring opening of the cyclic monomer is slow,
      leading to a lower initiator concentration than that produced by the cyclic BA
      dimer and trimer. Similarly, the cyclic BS dimer produces PBS of higher molecular
      weight than that obtained from the cyclic BS trimer.

PMID- 18322910
TI  - Characterizing biodegradation of PLA and PLA-g-AA/starch films using a phosphate
      solubilizing bacillus species.
AB  - The use of PLA and PLA-g-AA/starch as materials for the controlled release of
      encapsulated PSB was evaluated. The results showed that the bacterium degraded
      both the PLA and the PLA-g-AA/starch composite films, resulting in cell release.
      Severe disruption of the film structure occurred after incubation for 60-90 d.
      The PLA-g-AA/starch (20 wt.-%) films were more biodegradable than those made of
      PLA and also suffered a more pronounced decrease in molecular weight and
      intrinsic viscosity. Although blending of starch appeared to enhance the
      biodegradability of the PLA films, the pattern of degradation was quite similar
      for both types of films. The rate of cell release depends on the biodegradability
      of the film.

PMID- 18322911
TI  - In situ mineralization of hydroxyapatite on electrospun chitosan-based
      nanofibrous scaffolds.
AB  - A biocomposite of hydroxyapatite (HAp) with electrospun nanofibrous scaffolds was
      prepared by using chitosan/polyvinyl alcohol (CS/PVA) and N-carboxyethyl
      chitosan/PVA (CECS/PVA) electrospun membranes as organic matrix, and HAp was
      formed in supersaturated CaCl2 and KH2PO4 solution. The influences of carboxylic
      acid groups in CECS/PVA fibrous scaffold and polyanionic additive poly(acrylic
      acid) (PAA) in the incubation solution on the crystal distribution of the HAp
      were investigated. Field-emission scanning electron microscopy (FE-SEM), energy
      dispersive spectroscopy (EDS), wide-angle X-ray diffraction (WAXD), and Fourier
      transform infrared (FTIR) were used to characterize the morphology and structure
      of the deposited mineral phase on the scaffolds. It was found that addition of
      PAA to the mineral solution and use of matrix with carboxylic acid groups
      promoted mineral growth and distribution of HAp. MTT testing and SEM imaging from
      mouse fibroblast (L929) cell culture revealed the attachment and growth of mouse
      fibroblast on the surface of biocomposite scaffold, and that the cell morphology
      and viability were satisfactory for the composite to be used in bioapplications.

PMID- 18322912
TI  - Synthetic mimicking of plant oils and comparison with naturally grown products in
      polyurethane synthesis.
AB  - The use of plant oils as industrial feedstocks can often be hampered by their
      lack of optimization towards a particular process, as well as their development
      being risky; growing suitable volumes of crops to test can take up to five years.
      To circumvent this, we aimed to discover a method that would mimic plant oil
      profiles in the laboratory, and show that they exhibited similar properties to
      the naturally grown plant oils in a given process. Using the synthesis of
      polyurethanes as an example, we have synthesized six different polymers and
      demonstrated that plant oils will produce polymers with similar physical
      properties to those oils mimicked in the laboratory. The use of this mimicking
      process can be extended to other types of polymers to obtain a method for
      predicting the properties of a given material based on the plant oil composition
      of a crop before it is grown in bulk.

PMID- 18322913
TI  - Synthesis, degradability, and drug releasing properties of methyl esters of
      fungal poly(beta,L-malic acid).
AB  - Methyl esters of microbial poly(beta,L-malic acid) for conversion degrees of 25,
      50, 75, and 100% were prepared by treatment of the polyacid with diazomethane.
      Esterification proceeded with retention of the molecular weight of the parent
      polyacid and the copolymers displayed a blocky microstructure consisting of short
      segments of malic and methyl malate sequences. The thermal stability of the
      copolyesters was lower than those of the parent homopolymers and all of them were
      fairly crystalline with melting temperatures within the range of 170-175 degrees
      C. They were degraded rapidly by water, the hydrolysis rate being highly
      dependent on the methylation degree. Microspheres with mean-average diameters in
      the range of 1-20 microm were prepared from the 100% methylated product by the
      emulsion-evaporation solvent method. Encapsulation of erythromycin was
      efficiently performed in these microparticles and its releasing upon incubation
      in simulated physiological medium was evaluated for different drug loads. Drug
      delivery was observed to occur by a releasing mechanism largely determined by the
      hydrodegradation of the host polymer and independent of the amount of loaded
      drug.

PMID- 18322914
TI  - Description of a return-to-work occupational therapy programme for stroke
      rehabilitation in Singapore.
AB  - Stroke is the fourth leading cause of death and the major cause of disability in
      Singapore. The number of stroke survivors is expected to rise with the increase
      in the ageing population. This paper describes how occupational therapists are
      involved in stroke and work rehabilitation in Singapore. A retrospective study of
      stroke clients referred to a vocational assessment unit in 2004 showed that 55%
      of the clients were able to return to work. The majority of the clients changed
      their job positions from blue-collar workers to clerical workers. On the other
      hand, the main reasons for poor outcome were: unfit to work in general, needed
      further rehabilitation, further medical care was indicated, failed to meet
      appointments and withdrawal from the job trial. Three case vignettes are
      discussed to illustrate the multifactorial aspects influencing positive work
      outcomes. Further research is needed in exploring the factors that affect stroke
      rehabilitation and return-to-work outcomes.

PMID- 18322915
TI  - Genetic variation in the enigmatic Altaian Kazakhs of South-Central Russia:
      insights into Turkic population history.
AB  - The Altaian Kazakhs, a Turkic speaking group, now reside in the southern part of
      the Altai Republic in south-central Russia. According to historical accounts,
      they are one of several ethnic and geographical subdivisions of the Kazakh
      nomadic group that migrated from China and Western Mongolia into the Altai region
      during the 19th Century. However, their population history of the Altaian Kazakhs
      and the genetic relationships with other Kazakh groups and neighboring Turkic
      speaking populations is not well understood. To begin elucidating their genetic
      history, we analyzed the mtDNAs from 237 Altaian Kazakhs through a combination of
      SNP analysis and HVS1 sequencing. This analysis revealed that their mtDNA gene
      pool was comprised of roughly equal proportions of East (A-G, M7, M13, Y and Z)
      and West (H, HV, pre-HV, R, IK, JT, X, U) Eurasian haplogroups, with the
      haplotypic diversity within haplogroups C, D, H, and U being particularly high.
      This pattern of diversity likely reflects the complex interactions of the Kazakhs
      with other Turkic groups, Mongolians, and indigenous Altaians. Overall, these
      data have important implications for Kazakh population history, the genetic
      prehistory of the Altai-Sayan region, and the phylogeography of major
      mitochondrial lineages in Eurasia.

PMID- 18322916
TI  - Morphological integration and natural selection in the postcranium of wild
      verreaux's sifaka (Propithecus verreauxi verreauxi).
AB  - Morphological integration manifests as strong phenotypic covariation among
      interacting traits. In this study, a graph-theory approach is used to analyze
      patterns of morphological integration in a wild population of Verreaux's sifaka
      (Propithecus verreauxi verreauxi). The motivation for this study is to determine
      the relative roles of development versus function in shaping patterns of
      morphological integration in the sifaka postcranium. A developmental and a
      functional hypothesis of integration are compared with the observed pattern of
      integration and the fit of these hypotheses is assessed using information
      theoretic statistics. Correlational selection is also estimated on limb elements.
      Information theoretic statistics indicate that the developmental hypothesis fits
      the observed pattern of integration slightly better than the functional
      hypothesis. Only two pairs of traits experience correlational selection but
      neither of the traits within each pair are morphologically integrated. The
      observed pattern of integration contains several trait-trait associations that
      are specified by both the functional and developmental hypotheses. These results
      likely reflect the nested covariation structure in which a novel locomotor mode,
      vertical clinging and leaping, is derived from a primitive quadrupedal
      morphotype.

PMID- 18322917
TI  - Grandmothers' longevity negatively affects daughters' fertility.
AB  - The evolution of postmenopausal longevity in human females has been the subject
      of debate. Specifically, there is disagreement about whether the evolution of the
      trait should be understood as an adaptive or a neutral process, and if the
      former, what the selective mechanism is. There are two main adaptive proposals to
      explain the evolution of postreproductive longevity: the grandmother and the
      mother hypotheses. The grandmother hypothesis proposes that postreproductive
      longevity evolved because it is selectively advantageous for females to stop
      reproducing and to help raise their grandchildren. The mother hypothesis states
      that postmenopausal longevity evolved because it is advantageous for women to
      cease reproduction and concentrate their resources and energy in raising the
      children already produced. In this article, we test the mother and the
      grandmother hypotheses with a historical data set from which we bootstrapped
      random samples of women from different families who lived from the 1500s to the
      1900s in the central valley of Costa Rica. We also compute the heritability of
      longevity, which allows us to determine if genes involved in longevity are nearly
      fixed in this population. Here we show that although longevity positively affects
      a woman's fertility, it negatively affects her daughter's fertility; for this
      reason, the heritability of longevity is unexpectedly high. Our data provide
      strong grounds for questioning the universality of the grandmother hypothesis and
      for supporting the mother hypothesis as a likely explanation for the evolution of
      human postreproductive longevity.

PMID- 18322918
TI  - Brief communication: new evidence of tuberculosis from prehistoric Korea
      Population movement and early evidence of tuberculosis in far East Asia.
AB  - Tuberculosis has been recognized in Japan and Korea for more than 500 years in
      historical medical documents. However, the origin and early existence of
      tuberculosis is poorly understood in these regions. Very recently, skeletal
      evidence for tuberculosis from the Bronze Age (or Aneolithic) period was reported
      from Japan and Korea. This article describes a possible case of spinal
      tuberculosis from an archeological site in Korea, which was dated to the first
      century BC. This date corresponds to the Aneolithic (Yayoi) period in Japan.
      Skeletal evidence for tuberculosis during the Bronze Age period found in both
      Korea and Japan are, therefore, discussed as evidence of the earliest
      tuberculosis outbreaks in East Asia and as biological indicators of population
      movement between Korea and Japan during this period.

PMID- 18322919
TI  - Senescence of reproduction may explain adaptive menopause in humans: a test of
      the "mother" hypothesis.
AB  - The "mother" hypothesis is one of the main adaptive explanations of human
      menopause. It postulates that reproductive cessation constitutes a strategy that
      has been selected for during human evolution because mothers at older ages might
      maximize their fitness by investing resources in the survival and reproduction of
      their living children rather than by continuing to reproduce. This study provides
      a test of this hypothesis. Fertility functions that maximize fitness are built
      into a model incorporating the fact that the survival of females during the
      rearing period is a major determinant of their children's survival. Results are
      given according to different scenarios of increase with mothers' age of maternal
      mortality risk and risk of stillbirth and birth defects (on the assumption that
      these females do not experience menopause). Different estimates of the effect of
      a mother's death on her child's survival were also incorporated. Finally, a
      population genetics framework allows us to estimate selection on these optimal
      fertility functions. To determine whether or not these fertility functions show a
      menopause, three criteria are discussed: the rapidity of fertility decline, if
      any; the magnitude of selection on menopause compared with a nonmenopausal
      strategy; and the selection on survival during post-reproductive life. Our
      results show that menopause and subsequent post-reproductive life are
      significantly advantageous when two conditions are satisfied: a marked increase
      in stillbirth and risk of birth defects as well as in maternal mortality with
      mother's age.

PMID- 18322920
TI  - Retrograde analysis of the cerebellar projections to the posteroventral part of
      the ventral lateral thalamic nucleus in the macaque monkey.
AB  - The organization of cerebellothalamic projections was investigated in macaque
      monkeys using injections of retrograde tracers (cholera toxin B and fluorescent
      dextrans) in the posteroventral part of the ventrolateral thalamic nucleus
      (VLpv), the main source of thalamic inputs to the primary motor cortex.
      Injections that filled all of VLpv labeled abundant neurons that were
      inhomogeneously distributed among many unlabeled cells in the deep cerebellar
      nuclei (DCbN). Single large pressure injections made in face-, forelimb-, or
      hindlimb-related portions of VLpv using physiological guidance labeled numerous
      neurons that were broadly dispersed within a coarse somatotopographic
      anteroposterior (foot to face) gradient in the dentate and interposed nuclei.
      Small iontophoretic injections labeled fewer neurons with the same
      somatotopographic gradient, but strikingly, the labeled neurons in these cases
      were as broadly dispersed as in cases with large injections. Simultaneous
      injections of multiple tracers in VLpv (one tracer per somatic region with no
      overlap between injections) confirmed the general somatotopography but also
      demonstrated clearly the overlapping distributions and the close intermingling of
      neurons labeled with different tracers. Significantly, very few neurons (<2%)
      were double-labeled. This organizational pattern contrasts with the concept of a
      segregated "point-to-point" somatotopy and instead resembles the complex patterns
      that have been observed throughout the motor pathway. These data support the idea
      that muscle synergies are represented anatomically in the DCbN by a general
      somatotopography in which intermingled neurons and dispersed but selective
      connections provide the basis for plastic, adaptable movement coordination of
      different parts of the body. Indexing terms:

PMID- 18322921
TI  - Retrograde analyses of spinothalamic projections in the macaque monkey: input to
      the ventral lateral nucleus.
AB  - The distribution of retrogradely labeled spinothalamic tract (STT) neurons was
      analyzed in monkeys following variously sized injections of cholera toxin subunit
      B (CTb) in order to determine whether different STT termination sites receive
      input from different sets of STT cells. This report focuses on STT input to the
      ventral lateral nucleus (VL), where prior anterograde tracing studies identified
      dense or moderately dense STT terminations. Large and very large injections in VL
      produced large numbers of labeled cells predominantly in laminae V and VII (more
      than half as many as from massive injections in the entire thalamus). Medium
      sized and small injections in VL labeled STT cells almost exclusively in laminae
      V and VII, in segments consistent with the coarse mediolateral VL topography; few
      or no cells were labeled in lamina I. All injections labeled the deep cerebellar
      nuclei (see accompanying article: Evrard and Craig, 2008). Notably, even the most
      anterior injection in VL that produced dense pallidal labeling still labeled both
      STT and deep cerebellar cells. These observations indicate that VL receives STT
      input originating from laminae V and VII neurons that may be coextensive with its
      cerebellothalamic input. These findings support the role of laminae V and VII STT
      cells in sensorimotor integration and suggest a significant ongoing influence on
      both motor and premotor thalamocortical function. Together with the preceding
      observations of selective STT projections to other thalamic regions, these
      results provide compelling evidence that the primate STT consists of anatomically
      and functionally differentiable components.

PMID- 18322922
TI  - Expression analysis of cadherins in the songbird brain: relationship to vocal
      system development.
AB  - Songbirds learn their songs as juveniles. The brains of songbirds have a series
      of nuclei and neural circuits called the song system, which is indispensable for
      vocal learning and production. In the present study we analyzed the expression
      patterns of cell adhesion molecules, cadherins, in the Bengalese finch (Lonchura
      striata var. domestica) to investigate their potential involvement in song nuclei
      and neural circuit formation. We found that cadherin-6B was expressed in many
      song nuclei of the juvenile and adult brain, while R-cadherin was complementarily
      expressed in surrounding areas. On the other hand, cadherin-7 was expressed in
      the robust nucleus of the arcopallium (RA) in the sensory learning stage, and its
      expression was downregulated during the sensorimotor learning stage. This
      downregulation of cadherin-7 was sexually dimorphic, suggesting its involvement
      in song development. Other cadherins, including cadherin-9, -10, and -12, showed
      different song-nuclei-related expression profiles. These patterns of song nuclei
      related expression suggest the possibility that cadherins are involved in the
      formation and maintenance of the song nuclei or neural pathways of the song
      system.

PMID- 18322923
TI  - The functions of the "Greeting Ceremony" among male mantled howlers (Alouatta
      palliata) on Agaltepec Island, Mexico.
AB  - Nonhuman primates use greeting behaviors as nonaggressive communicatory signals
      in multiple social contexts. Adult male mantled howlers (Alouatta palliata)
      perform a ritual greeting that has been associated with bond-strengthening
      functions. The aim of this study is to explore the greeting patterns of male
      howlers living on Agaltepec Island, Mexico. Specifically, we analyzed the
      relationships between greetings and several individual, relational, and
      contextual variables, such as the expression of affiliation and agonism,
      dominance rank, age, kinship relationships, spatial organization, activity
      patterns, and subgrouping patterns. Greetings were more frequent between males
      with closer dominance ranks. Among those dyads that greeted at least once,
      dominant males initiated greetings more frequently than less-dominant males. On
      the other hand, more greetings were observed when one of the participants had
      recently returned to a subgroup and during locomotion. On the basis of these
      results, we propose that on Agaltepec greetings are a conflict management
      mechanism used between males of similar ranks. The fission-fusion social system
      of this group of howlers allows males with conflicting interests to remain
      separated, and greetings may reduce tension during fusion events.

PMID- 18322924
TI  - Retinal hemorrhages requiring vitrectomy in a patient with hemophagocytic
      lymphohistiocytosis.

PMID- 18322925
TI  - A meta-analysis of the neuropsychological sequelae of chemotherapy-only treatment
      for pediatric acute lymphoblastic leukemia.
AB  - BACKGROUND: Mixed findings on the neuropsychological sequelae of chemotherapy
      only treatment for pediatric acute lymphoblastic leukemia (ALL), without
      radiation, indicate the need for a comprehensive meta-analytic review. The
      purpose of the current study was to conduct a meta-analysis assessing
      neuropsychological and academic functioning differences between children with ALL
      treated solely with chemotherapy and comparison groups. PROCEDURE: Thirteen
      articles met inclusion criteria for the meta-analysis and were analyzed using a
      random effects model, weighted least squares methods. RESULTS: Mean effect sizes
      were significantly different from zero for multiple domains of intelligence and
      academic achievement; processing speed; verbal memory; and some aspects of
      executive functioning and fine motor skills, indicating worse functioning in ALL
      survivors. Effect sizes for visual-motor skills and visual memory were not
      significantly different from zero. CONCLUSIONS: Results support the presence of
      neuropsychological and academic sequelae for ALL survivors treated solely with
      chemotherapy and highlight the need for ongoing follow-up of children with ALL
      using a standardized neuropsychological test battery and research methodology.

PMID- 18322926
TI  - Chemotoxicity recovery of mitochondria in non-Hodgkin lymphoma resulting in
      minimal residual disease.
AB  - BACKGROUND: The mechanisms responsible for resistant disease or recurrence of non
      Hodgkin lymphoma (NHL) in children cover a wide spectrum from drug resistance to
      genetic mutations. A unique mechanism suggesting the role of mitochondria as the
      key energy source is studied following a clinical observation where pediatric
      Burkitt lymphoma (BL) specimens from patients on therapy were found to have
      increased copies of mitochondria DNA (mtDNA) in specimens which were shown to be
      positive for minimal residual disease and/or persistent disease (MRD/PD). This
      study hypothesized that the mitochondria play an important role in a cell's
      recovery from toxicity via a compensatory increase in mtDNA. PROCEDURE: BL
      specimens with MRD/PD were assayed for mtDNA. An in vitro model was then designed
      using Ramos cell lines by exposing the lymphoma cells to varying concentrations
      of doxorubicin and vincristine for 1 hr; and allowing for recovery in culture
      over 7 days. DNA was extracted from aliquots over several days to determine mtDNA
      copy numbers by real-time polymerase chain reaction (PCR). RESULTS: Increased
      mtDNA copy numbers were found in clinical specimens with MRD/PD as well as in
      recovering Ramos cells from chemotoxicity. CONCLUSIONS: The recovering lymphoma
      cells from the chemotoxic effects appeared to compensate by increasing mtDNA
      content, which may contribute to the clinical residual or resistant disease in
      some cases of childhood BL.

PMID- 18322927
TI  - Shwachman-Diamond syndrome presenting in a premature infant as pancytopenia.
AB  - Shwachman-Diamond syndrome is a rare autosomal recessive disorder characterized
      by bone marrow dysfunction, exocrine pancreatic insufficiency, failure to thrive,
      and skeletal abnormalities. It is most commonly diagnosed in early childhood
      after the development of hematologic abnormalities. We report a premature infant
      born at 33 weeks gestation who was small for gestational age and displayed
      persistent cytopenias requiring transfusion. Genetic testing confirmed a
      diagnosis of Shwachman-Diamond syndrome (SDS).

PMID- 18322928
TI  - Lifestyle regularity and cyclothymic symptomatology.
AB  - The social zeitgeber theory emphasizes the importance that social rhythm
      regularity may play in promoting internal synchronization of circadian rhythms in
      individuals with or at risk for bipolar spectrum disorders. This study examined
      the relationship of lifestyle regularity, affective symptomatology, and sleep in
      71 individuals exhibiting cyclothymic mood and behavior patterns. Participants
      were randomly assigned to either an experimental group in which they were
      encouraged to regulate their daily routines or to a control group. Participants
      in the experimental group were able to successfully regulate their daily
      schedules. Although relationships between regularity and severity of depressive
      symptoms, across-day variances in mood and behavior, and sleep duration were
      identified during baseline, increased lifestyle regularity did not differentially
      result in changes in these variables.

PMID- 18322929
TI  - Contexts of rubbing behavior in Alouatta guariba clamitans: a scent-marking role?
AB  - Rubbing behaviors are well known in several primate species and are usually seen
      as scent-marking behaviors, with several functions proposed but still widely
      debated. The genus Alouatta is highly sexually dimorphic and a suitable subject
      for the study of sexual and hierarchical divergences associated with rubbing
      behavior: males should mark more than females, and dominant individuals more than
      subordinate ones. Three wild groups of Southern brown howler monkeys, Alouatta
      guariba clamitans, were studied at Morro Geisler, Indaial, Brazil, from September
      2004 to February 2005. One hundred and twenty-three rubbing episodes were
      registered; data on performers and associated contexts showed that anogenital,
      dorsum and hyoid regions were the most often rubbed. Adult males rubbed
      significantly above expected levels, whereas subordinated females and juveniles
      tended to rub below the expected levels. Females were the main performers of
      anogenital rubbing, often preceded by defecation. The predominance of rubbing in
      males probably serves an important function in intrasexual communication and
      social interactions. Intrasexual competition can also lead to a relationship
      between rubbing and social status in females. Hyoid and sternum rubbing by males
      are probably agonistic signals associated with extragroup conflict. The possible
      cleaning function of anogenital rubbing does not preclude a communicative
      function. Whether rubbing behavior in howlers is solely for the function of scent
      marking or can also be a visual signal (e.g. as a display or to color the
      substrate with pigment) requires further study.

PMID- 18322930
TI  - Structure and chain conformation of beta-glucan isolated from Auricularia
      auricula-judae.
AB  - From Auricularia auricula-judae, a water soluble beta-D-glucan, named as AAG, was
      isolated by extraction with 70% ethanol/water solution. Its chemical structure
      was analyzed by gas chromatography (GC), gas chromatography-mass spectrometry (GC
      MS), matrix-assisted laser desorption /ionization (MALDI)-time of flight (TOF),
      and 1D, 2D NMR. AAG was detected, for the first time, to be composed of a main
      chain of (1-->4)-linked D-glucopyranosyl with glucopyranosyl side groups at O6.
      With the help of MALDI-TOF-MS, the sequence and the distribution of glucuronic
      acid were determined and the content of glucuronic acid is about 19%. Five
      fractions were prepared from the AAG sample in water by ultrasonic degradation
      method. Their molecular weight, size, and shape (chain conformation) were studied
      by dynamics light scattering (DLS), static laser light scattering (LLS), size
      exclusion chromatography combined LLS (SEC-LLS) and viscometry in 0.1M NaCl
      aqueous solution at 25 degrees C. The dependence of intrinsic viscosity ([eta])
      on Mw for this polysaccharide was established to be [eta] = 1.22 x10(-3)Mw (1.00)
      (cm3 g(-1)) in the range of Mw from 3.40 x 10(4) to 2.88 x 10(5). The
      conformational parameters of the AAG polysaccharide were found to be 820 nm(-1)
      for molar mass per unit contour length (ML), 12.3 nm for persistence length (q)
      and 2.1 for rho (s2(1/2)/Rh). The results suggested that the polysaccharide
      exists as extended chains in 0.1M NaCl aqueous solution. The chemical structure
      of AAG containing glucuronic acid and side groups led to steric hindrance,
      resulting in the increased stiffness of the chains.

PMID- 18322931
TI  - Reductive unfolding of serum albumins uncovered by Raman spectroscopy.
AB  - The reductive unfolding of bovine serum albumin (BSA) and human serum albumin
      (HSA) induced by dithiothreitol (DTT) is investigated using Raman spectroscopy.
      The resolution of the S-S Raman band into both protein and oxidized DTT
      contributions provides a reliable basis for directly monitoring the S-S bridge
      exchange reaction. The related changes in the protein secondary structure are
      identified by analyzing the protein amide I Raman band. For the reduction of one
      S-S bridge of BSA, a mean Gibbs free energy of -7 kJ mol(-1) is derived by
      studying the reaction equilibrium. The corresponding value for the HSA S-S bridge
      reduction is -2 kJ mol(-1). The reaction kinetics observed via the S-S or amide I
      Raman bands are identical giving a reaction rate constant of (1.02 +/- 0.11) M(
      1) s(-1) for BSA. The contribution of the conformational Gibbs free energy to the
      overall Gibbs free energy of reaction is further estimated by combining
      experimental data with ab initio calculations.

PMID- 18322932
TI  - Hyaluronic acid-polyethyleneimine conjugate for target specific intracellular
      delivery of siRNA.
AB  - A novel target specific small interfering RNA (siRNA) delivery system was
      successfully developed using polyethyleneimine (PEI)-hyaluronic acid (HA)
      conjugate. Anti-PGL3-Luc siRNA was used as a model system suppressing the PGL3
      Luc gene expression. The siRNA/PEI-HA complex with an average size of ca. 21 nm
      appeared to be formed by electrostatic interaction between the negatively charged
      siRNA and the positively charged PEI of PEI-HA conjugate. The cytotoxicity of
      siRNA/PEI-HA complex to B16F1 cells was lower than that of siRNA/PEI complex
      according to the MTT assay. When B16F1 and HEK-293 cells were treated with
      fluorescein isothiocyanate (FITC) labeled siRNA/PEI-HA complex, B16F1 cells, with
      a lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), showed higher
      green fluorescent intensity than HEK-293 cells because of the HA receptor
      mediated endocytosis of the complex. Accordingly, the PGL3-Luc gene silencing of
      anti-PGL3-Luc siRNA/PEI-HA complex was more efficient in B16F1 cells than in HEK
      293 cells. In addition, the inhibited PGL3-Luc gene silencing effect in the
      presence of free HA in the transfection medium revealed that siRNA/HA-PEI complex
      was selectively taken up to B16F1 cells via HA receptor mediated endocytosis. All
      these results demonstrated that the intracellular delivery of anti-PGL3-Luc
      siRNA/PEI-HA complex could be facilitated by the HA receptor mediated
      endocytosis.

PMID- 18322936
TI  - Development of novel agents for the treatment of hepatitis C virus.

PMID- 18322938
TI  - To define virological response in hepatitis B e antigen-negative patients.

PMID- 18322939
TI  - Metabolic interactions of agrochemicals in humans.
AB  - Agrochemicals and other xenobiotics are metabolized by xenobiotic-metabolizing
      enzymes (XMEs) to products that may be more or less toxic than the parent
      chemical. In this regard, phase-I XMEs such as cytochrome P450s (CYPs) are of
      primary importance. Interactions at the level of metabolism may take place via
      either inhibition or induction of XMEs. Such interactions have often been
      investigated, in vitro, in experimental animals, using subcellular fractions such
      as liver microsomes, but seldom in humans or at the level of individual XME
      isoforms. The authors have been investigating the metabolism of a number of
      agrochemicals by human liver microsomes and recombinant CYP isoforms and have
      recently embarked on studies of the induction of XMEs in human hepatocytes. The
      insecticides chlorpyrifos, carbaryl, carbofuran and fipronil, as well as the
      repellant DEET, are all extensively metabolized by human liver microsomes and,
      although a number of CYP isoforms may be involved, CYP2B6 and CYP3A4 are usually
      the most important. Permethrin is hydrolyzed by esterase(s) present in both human
      liver microsomes and cytosol. A number of metabolic interactions have been
      observed. Chlorpyrifos and other phosphorothioates are potent inhibitors of the
      CYP-dependent metabolism of both endogenous substrates, such as testosterone and
      estradiol, and exogenous substrates, such as carbaryl, presumably as a result of
      the interaction of highly reactive sulfur, released during the oxidative
      desulfuration reaction, with the heme iron of CYP. The hydrolysis of permethrin
      in human liver can be inhibited by chlorpyrifos oxon and by carbaryl. Fipronil
      can inhibit testosterone metabolism by CYP3A4 and is an effective inducer of CYP
      isoforms in human hepatocytes.

PMID- 18322940
TI  - Efficiency of bowel preparation for capsule endoscopy examination: a meta
      analysis.
AB  - Good preparation before endoscopic procedures is essential for successful
      visualization. The small bowel is difficult to evaluate because of its length and
      complex configuration. A meta-analysis was conducted of studies comparing small
      bowel visualization by capsule endoscopy with and without preparation. Medical
      data bases were searched for all studies investigating the preparation for
      capsule endoscopy of the small bowel up to July 31, 2007. Studies that scored
      bowel cleanness and measured gastric and small bowel transit time and rate of
      cecum visualization were included. The primary endpoint was the quality of bowel
      visualization. The secondary endpoints were transit times and proportion of
      examinations that demonstrated the cecum, with and without preparation. Meta
      analysis was performed with StatDirect Statistical software, version 2.6.1
      (http://statsdirect.com). Eight studies met the inclusion criteria. Bowel
      visualization was scored as "good" in 78% of the examinations performed with
      preparation and 49% performed without (P<0.0001). There were no significant
      differences in transit times or in the proportion of examinations that
      demonstrated the cecum with and without preparation. Capsule endoscopy
      preparation improves the quality of small bowel visualization, but has no effect
      on transit times, or demonstration of the cecum.

PMID- 18322941
TI  - Proton pump inhibitors and an emerging epidemic of gastric fundic gland
      polyposis.
AB  - Fundic gland polyps are now commonly recognized during endoscopy. These polyps
      are benign, often multiple and usually detected in the gastric body and fundus.
      In the past, these polyps were sometimes associated with familial adenomatous
      polyposis. In recent years, it has become evident that increasing numbers of
      these polyps are being detected during endoscopic studies, particularly in
      patients treated with proton pump inhibitors for prolonged periods. In some,
      dysplastic changes in these polyps have also been reported. Recent studies have
      suggested that there may be no increase in risk of colon cancer with long-term
      proton pump inhibitor therapy. While temporarily reassuring, ongoing vigilance,
      particularly in those genetically predisposed to colon cancer, is still
      warranted.

PMID- 18322942
TI  - Feasibility of herpes simplex virus type 1 mutants labeled with radionuclides for
      tumor treatment.
AB  - For over one hundred years, viruses have been recognized as capable of killing
      tumor cells. At present, people are still researching and constructing more
      suitable oncolytic viruses for treating different malignant tumors. Although
      extensive studies have demonstrated that herpes simplex virus type 1 (HSV-1) is
      the most potential oncolytic virus, therapies based on herpes simplex virus type
      1 vectors still arouse bio-safety and risk management issues. Researchers have
      therefore introduced the new idea of treating cancer with HSV-1 mutants labeled
      with radionuclides, combining radionuclide and oncolytic virus therapies. This
      overview briefly summarizes the status and mechanisms by which oncolytic viruses
      kill tumor cells, discusses the application of HSV-1 and HSV-1 derived vectors
      for tumor therapy, and demonstrates the feasibility and prospect of HSV-1 mutants
      labeled with radionuclides for treating tumors.

PMID- 18322943
TI  - Management of inflammatory bowel disease in the pregnant patient.
AB  - Inflammatory bowel disease (IBD) is a chronic disorder affecting young adults in
      their reproductive years. Many young women with IBD express concern about the
      effect their disease will have on fertility, pregnancy course and fetal
      development. This article presents an approach to management of IBD in the
      pregnant patient, including counseling and investigation, and summarizes existing
      data on the safety of medications used to treat IBD in pregnancy and
      breastfeeding.

PMID- 18322944
TI  - Isolation and bioinformatics analysis of differentially methylated genomic
      fragments in human gastric cancer.
AB  - AIM: To isolate and analyze the DNA sequences which are methylated differentially
      between gastric cancer and normal gastric mucosa. METHODS: The differentially
      methylated DNA sequences between gastric cancer and normal gastric mucosa were
      isolated by methylation-sensitive representational difference analysis (MS-RDA).
      Similarities between the separated fragments and the human genomic DNA were
      analyzed with Basic Local Alignment Search Tool (BLAST). RESULTS: Three
      differentially methylated DNA sequences were obtained, two of which have been
      accepted by GenBank. The accession numbers are AY887106 and AY887107. AY887107
      was highly similar to the 11th exon of LOC440683 (98%), 3' end of LOC440887
      (99%), and promoter and exon regions of DRD5 (94%). AY887106 was consistent (98%)
      with a CpG island in ribosomal RNA isolated from colorectal cancer by Minoru
      Toyota in 1999. CONCLUSION: The methylation degree is different between gastric
      cancer and normal gastric mucosa. The differentially methylated DNA sequences can
      be isolated effectively by MS-RDA.

PMID- 18322945
TI  - Increased hepcidin expression in colorectal carcinogenesis.
AB  - AIM: To investigate whether the iron stores regulator hepcidin is implicated in
      colon cancer-associated anaemia and whether it might have a role in colorectal
      carcinogenesis. METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was
      employed to measure hepcidin in urine collected from 56 patients with colorectal
      cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA
      expression in colorectal cancer tissue. Hepcidin cellular localisation was
      determined using immunohistochemistry. RESULTS: We demonstrate that whilst
      urinary hepcidin expression was not correlated with anaemia it was positively
      associated with increasing T-stage of colorectal cancer (P<0.05). Furthermore, we
      report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue
      specimens and was correlated with ferroportin repression. This was supported by
      hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION: We demonstrate
      that systemic hepcidin expression is unlikely to be the cause of the systemic
      anaemia associated with colorectal cancer. However, we demonstrate for the first
      time that hepcidin is expressed by colorectal cancer tissue and that this may
      represent a novel oncogenic signalling mechanism.

PMID- 18322946
TI  - COOH-terminal deletion of HBx gene is a frequent event in HBV-associated
      hepatocellular carcinoma.
AB  - AIM: To investigate the hepatitis B virus (HBV)x gene (HBx) state in the tissues
      of HBV-related hepatocellular carcinoma (HCC) in Chinese patients and whether
      there were particular HBx mutations. METHODS: HBx gene was amplified and direct
      sequencing was used in genomic DNA samples from 20 HCC and corresponding non
      cancerous liver tissues from HBsAg-positive patients. HBV DNA integration and HBx
      deleted mutation were validated in 45 HCC patients at different stages by
      Southern blot analysis and polymerase chain reaction methods. RESULTS: The
      frequencies of HBx point mutations were significantly lower in HCC than their
      corresponding non-cancerous liver tissues (11/19 vs 18/19, P=0.019). In contrast,
      deletions in HBx gene were significantly higher in HCC than their non-cancerous
      liver tissues (16/19 vs 4/19, P<0.001). The deletion of HBx COOH-terminal was
      detected in 14 HCC tissues. A specific integration of HBx at 17p13 locus was also
      found in 8 of 16 HCC, and all of them also exhibited full-length HBx deletions.
      Integrated or integrated coexistence with replicated pattern was obtained in
      45.5% (20/45)-56.8% (25/45) tumors and 40.9% (18/45)-52.3% (23/45) non-tumor
      tissues. CONCLUSION: HBx deletion, especially the COOH-terminal deletion of HBx
      is a frequent event in HBV-associated HCC tissues in China. HBV integration had
      also taken place in partial HCC tissues. This supporting the hypothesis that
      deletion and probably integrated forms of the HBx gene may be implicated in liver
      carcinogenesis.

PMID- 18322947
TI  - Expression of tumor necrosis factor-alpha converting enzyme in liver regeneration
      after partial hepatectomy.
AB  - AIM: To study the expression of tumor necrosis factor-alpha converting enzyme
      (TACE) and evaluate its significance in liver regeneration after partial
      hepatectomy in vivo. METHODS: Male SD rats underwent 70% partial hepatectomy. The
      remaining liver and spleen tissue samples were collected at indicated time points
      after hepatectomy. TACE expression was investigated by Western blotting,
      immunohistochemistry, and serial section immunostaining. RESULTS: Expression of
      TACE in liver and spleen tissues after partial hepatectomy was a time-dependent
      alteration, reaching a maximal level between 24 and 48 h and remaining elevated
      for more than 168 h. TACE protein was localized to mononuclear cells (MNC), which
      infiltrated the liver from the spleen after hepatectomy. The kinetics of TACE
      expression was in accordance with the number of TACE-staining MNCs and
      synchronized with those of transforming growth factor-alpha (TGFalpha). In
      addition, TACE-staining MNC partially overlapped with CD3+ T lymphocytes.
      CONCLUSION: TACE may be involved in liver regeneration by pathway mediated with
      TGFalpha-EGFR in the cell-cycle progressive phase in vivo. TACE production and
      effect by paracrine may be a pathway of involvement in liver regeneration for the
      activated CD3+ T lymphocytes.

PMID- 18322948
TI  - Prevalence of gastroesophageal reflux symptoms in a large unselected general
      population in Japan.
AB  - AIM: To examine the prevalence of gastroesophageal reflux disease (GERD) symptoms
      in a large unselected general population in Japan. METHODS: In Japan, mature
      adults are offered regular check-ups for the prevention of gastric cancer. A
      notice was sent by mail to all inhabitants aged>40 years. A total of 160983
      Japanese (60774 male, 100209 female; mean age 61.9 years) who underwent a stomach
      check up were enrolled in this study. In addition, from these 160983 subjects, we
      randomly selected a total of 82894 (34275 male, 48619 female; mean age 62.4
      years) to evaluate the prevalence of abdominal pain. The respective subjects were
      prospectively asked to complete questionnaires concerning the symptoms of
      heartburn, dysphagia, and abdominal pain for a 1 mo period. RESULTS: The
      respective prevalences of the symptoms in males and females were: heartburn,
      15.8% vs 20.7%; dysphagia, 5.4% vs 7.8%; and abdominal pain, 6.6% vs 9.6%. Among
      these symptoms, heartburn was significantly high compared with the other
      symptoms, and the prevalence of heartburn was significantly more frequent in
      females than in males in the 60-89-year age group. Dysphagia was also
      significantly more frequent in female patients. CONCLUSION: The prevalence of
      typical GERD symptoms (heartburn) was high, at about 20% of the Japan population,
      and the frequency was especially high in females in the 60-89 year age group.

PMID- 18322949
TI  - Absence of Na+/sugar cotransport activity in Barrett's metaplasia.
AB  - AIM: To evaluate the presence of Na+-dependent, active, sugar transport in
      Barrett's epithelia as an intestinal biomarker, based on the well-documented,
      morphological intestinal phenotype of Barrett's esophagus (BE). METHODS: We
      examined uptake of the nonmeta-bolizable glucose analogue, alpha-methyl-D
      glucoside (AMG), a substrate for the entire sodium glucose cotransporter (SGLT)
      family of transport proteins. During upper endoscopy, patients with BE or with
      uncomplicated gastroesophageal reflux disease (GERD) allowed for duodenal,
      gastric fundic, and esophageal mucosal biopsies to be taken. Biopsies were
      incubated in bicarbonate-buffered saline (KRB) containing 0.1 mmol/L 14C-AMG for
      60 min at 20 centigrade. Characterized by abundant SGLT, duodenum served as a
      positive control while gastric fundus and normal esophagus, known to lack SGLT,
      served as negative controls. RESULTS: Duodenal biopsies accumulated 249.84+/
      35.49 (SEM) picomoles AMG/microg DNA (n=12), gastric fundus biopsies 36.20+/-6.62
      (n=12), normal esophagus 12.10+/-0.59 (n=3) and Barrett's metaplasia 29.79+/-5.77
      (n=8). There was a statistical difference (P<0.01) between biopsies from duodenum
      and each other biopsy site but there was no statistically significant difference
      between normal esophagus and BE biopsies. 0.5 mmol/L phlorizin (PZ) inhibited AMG
      uptake into duodenal mucosa by over 89%, but had no significant effect on AMG
      uptake into gastric fundus, normal esophagus, or Barrett's tissue. In the absence
      of Na+ (all Na+ salts replaced by Li+ salts), AMG uptake in duodenum was
      decreased by over 90%, while uptake into gastric, esophageal or Barrett's tissue
      was statistically unaffected. CONCLUSION: Despite the intestinal enterocyte
      phenotype of BE, Na+-dependent, sugar transport activity is not present in these
      cells.

PMID- 18322950
TI  - Des-gamma-carboxy prothrombin as an important prognostic indicator in patients
      with small hepatocellular carcinoma.
AB  - AIM: To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on
      the invasiveness and prognosis of small hepatocellular carcinoma. METHODS: Among
      142 consecutive patients with known DCP levels, who underwent hepatectomy because
      of hepatocellular carcinoma, 85 patients met the criteria for small
      hepatocellular carcinoma, i.e. one<or=5 cm sized single tumor or no more than
      three<or=3 cm sized tumors. RESULTS: The overall survival rate of the 142
      patients was 92.1% for 1 year, 69.6% for 3 years, and 56.9% for 5 years.
      Multivariate analysis showed that microscopic vascular invasion (P=0.03) and
      serum DCP>or=400 mAU/mL (P=0.02) were independent prognostic factors. In the
      group of patients who met the criteria for small hepatocellular carcinoma,
      DCP>or=400 mAU/mL was found to be an independent prognostic factor for recurrence
      free (P=0.02) and overall survival (P=0.0005). In patients who did not meet the
      criteria, the presence of vascular invasion was an independent factor for
      recurrence-free (P=0.02) and overall survivals (P=0.01). In 75% of patients with
      small hepatocellular carcinoma and high DCP levels, recurrence occurred
      extrahepatically. CONCLUSION: For small hepatocellular carcinoma, a high
      preoperative DCP level appears indicative for tumor recurrence. Because many
      patients with a high preoperative DCP level develop extrahepatic recurrence, it
      is necessary to screen the whole body.

PMID- 18322951
TI  - MK615 inhibits pancreatic cancer cell growth by dual inhibition of Aurora A and B
      kinases.
AB  - AIM: To investigate the anti-neoplastic effect of MK615, an anti-neoplastic
      compound isolated from Japanese apricot, against human pancreatic cancer cells in
      vitro. METHODS: Three human pancreatic cancer cell lines PANC-1, PK-1, and PK45H
      were cultured with MK615 at concentrations of 600, 300, 150, and 0 microg/mL.
      Growth inhibition was evaluated by cell proliferation assay, and killing activity
      was determined by lactate dehydrogenase (LDH) assay. Expression of Aurora A and B
      kinases was detected by real-time polymerase chain reaction (PCR) and Western
      blotting. Cell cycle stages were evaluated by flow cytometry. RESULTS: The growth
      inhibitory rates of MK615 at 150, 300, and 600 microg/mL were 2.3%+/-0.9%, 8.9%+/
      3.2% and 67.1%+/-8.1% on PANC1 cells, 1.3%+/-0.3%, 8.7%+/-4.1% and 45.7+/-7.6% on
      PK1 cells, and 1.2+/-0.8%, 9.1%+/-2.1% and 52.1%+/-5.5% on PK45H cells,
      respectively (P<0.05). The percentage cytotoxicities of MK615 at 0, 150, 300, and
      600 microg/mL were 19.6%+/-1.3%, 26.7%+/-1.8%, 25.5%+/-0.9% and 26.4%+/-0.9% in
      PANC1 cells, 19.7%+/-1.3%, 24.7%+/-0.8%, 25.9%+/-0.9% and 29.9%+/-1.1% in PK1
      cells, and 28.0%+/-0.9%, 31.2%+/-0.9%, 30.4%+/-1.1% and 35.3+/-1.0% in PK45H
      cells, respectively (P<0.05). Real-time PCR and Western blotting showed that
      MK615 dually inhibited the expression of Aurora A and B kinases. Cell cycle
      analysis revealed that MK615 increased the population of cells in G2/M phase.
      CONCLUSION: MK615 exerts an anti-neoplastic effect on human pancreatic cancer
      cells in vitro by dual inhibition of Aurora A and B kinases.

PMID- 18322952
TI  - Management of cholelithiasis in Italian children: a national multicenter study.
AB  - AIM: To evaluate the management of Italian children with cholelithiasis observed
      at Pediatric and Surgical Departments linked to Italian Society of Pediatric
      Gastroenterology Hepatology and Nutrition. METHODS: One-hundred-eighty children
      (90 males, median age at diagnosis 7.3 years; range, 0-18 years) with echographic
      evidence of cholelithiasis were enrolled in the study; the data were collected by
      an anonymous questionnaire sent to participating centers. RESULTS: One hundred
      seventeen patients were treated with ursodeoxycholic acid; in 8 children
      dissolution of gallstones was observed, but the cholelithiasis recurred in 3 of
      them. Sixty-five percent of symptomatic children treated became asymptomatic.
      Sixty-four patients were treated with cholecystectomy and in only 2 cases a
      postoperative complication was reported. Thirty-four children received no
      treatment and were followed with clinical and echographic controls; in no case
      the development of complications was reported. CONCLUSION: The therapeutic
      strategies were extremely heterogeneous. Ursodeoxycholic acid was ineffective in
      dissolution of gallstones but it had a positive effect on the symptoms.
      Laparoscopic cholecystectomy was confirmed to be an efficacy and safe treatment
      for pediatric gallstones.

PMID- 18322953
TI  - Liver histology in ICU patients dying from sepsis: a clinico-pathological study.
AB  - AIM: To determine end-stage pathologic changes in the liver of septic patients
      dying in the intensive care unit. METHODS: Needle liver biopsies obtained
      immediately after death from 15 consecutive patients with sepsis and no
      underlying liver disease were subjected to routine histological examination.
      Liver function tests and clinical monitoring measurements were also recorded.
      RESULTS: Liver biochemistries were increased in the majority of patients before
      death. Histology of liver biopsy specimens showed portal inflammation in 73.3%,
      centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular
      apoptosis in 66.6% and cholangitis/cholangiolitis in 20% of patients. Mixed
      hepatitic/cholestatic type of liver injury was observed in 6/15 (40%) patients
      and hepatitc in 9/15 (60%). Steatosis was observed in 11/15 (73.3%) patients
      affecting 5%-80% of liver parenchyma. Among the histological features, the
      presence of portal inflammation in liver biopsy was associated with increased
      hospitalization in the ICU prior death (P=0.026). CONCLUSION: Features of
      hepatitis and steatosis are the main histological findings in the liver in the
      majority of patients dying from sepsis.

PMID- 18322954
TI  - Clinical significance of loss of heterozygosity for M6P/IGF2R in patients with
      primary hepatocellular carcinoma.
AB  - AIM: To investigate the relationship between loss of heterozygosity (LOH) for
      mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) and the
      outcomes for primary HCC patients treated with partial hepatectomy. METHODS: The
      LOH for M6P/IGF2R in primary HCC patients was assessed using six different gene
      specific nucleotide polymorphisms. The patients studied were enrolled to undergo
      partial hepatectomy. RESULTS: M6P/IGF2R was found to be polymorphic in 73.3%
      (22/30) of the patients, and of these patients, 50.0% (11/22) had tumors showing
      LOH in M6P/IGF2R. Loss of heterozygosity in M6P/IGF2R was associated with
      significant reductions in the two year overall survival rate (24.9% vs 65.5%;
      P=0.04) and the disease-free survival rate (17.8% vs 59.3%; P=0.03). CONCLUSION:
      These results show M6P/IGF2R LOH predicts poor clinical outcomes in surgically
      resected primary HCC patients.

PMID- 18322955
TI  - Intestinal permeability and its association with the patient and disease
      characteristics in Crohn's disease.
AB  - AIM: To assess the intestinal permeability (IP) in patients with Crohn's disease
      (CD) and study the association of IP with the patient and disease
      characteristics. METHODS: One hundred and twenty five consecutive patients of CD
      (Males: 66) were diagnosed on the basis of a combination of standard clinical,
      endoscopic, imaging and histological features. CD activity index (CDAI) was used
      to calculate the activity of the disease while the behavior of the disease was
      assessed by the modified Montreal classification. IP was measured by the ratio of
      the percentage excretion of ingested doses of lactulose and mannitol in urine
      (LMR). The upper limit of normality of LMR (0.037) was derived from 22 healthy
      controls. RESULTS: Thirty six percent of patients with CD had increased IP. There
      was no significant difference in mannitol excretion (patients vs controls=12.5%
      vs 14.2%, P=0.4652), but lactulose excretion was significantly higher in patients
      compared to healthy controls (patients vs controls=0.326% vs 0.293%, P=0.0391).
      The mean LMR was also significantly higher in the patients as compared to healthy
      controls [0.027 (0.0029-0.278) vs 0.0164 (0.0018-0.0548), P=0.0044]. Male
      patients had a higher LMR compared to females [0.036 (95% CI 0.029, 0.046) vs
      0.022 (95% CI 0.0178, 0.028) (P=0.0024), though there was no difference in the
      number of patients with abnormal IP in both the sexes. Patients with an ileo
      colonic disease had a higher LMR than those with only colonic disease [0.045 (95%
      CI 0.033, 0.06) vs 0.021 (95% CI 0.017, 0.025) (P<0.001)]. Of patients with ileo
      colonic disease, 57.8% had an abnormal IP, compared to 26.7% with colonic and
      15.6% with small intestinal disease. Patients with a stricturing disease had
      significantly higher LMR compared to non-fistulising non-stricturing disease
      [0.043 (95% CI 0.032, 0.058) vs 0.024 (95% CI 0.019, 0.029) (P=0.0062)]. There
      was no correlation of IP with age, disease activity, duration of illness, D
      xylose absorption, upper GI involvement, perianal disease, and extra-intestinal
      manifestations. On multiple regression analysis, male gender and ileo-colonic
      disease were independent factors associated with increased IP. Gender, location,
      behavior of the disease and upper GI involvement could explain up to 23% of
      variability in IP (R2=0.23). CONCLUSION: IP was increased in 36% of patients with
      CD. Male gender and an ileo-colonic disease were the independent factors
      associated with increased IP.

PMID- 18322956
TI  - Scintigraphic evaluation of gallbladder motor functions in H pylori positive and
      negative patients in the stomach with dyspepsia.
AB  - AIM: To evaluate the relationship between gallbladder (GB) motor function and H
      pylori infection in the stomach. METHODS: All cases (86) underwent the 14C urea
      breath test (UBT). 14C-UBT was found as positive in 58 and negative in 28
      dyspeptic patients. 14C-UBT was accepted as a gold standard test. Clo test and
      histopathologic examination were compared with the results of 14C-UBT in cases
      who tolerated upper gastrointestinal endoscopy procedure. Cholescintigraphy with
      99mTc-mebrofenin was used to determine the parameters of GB motor function (GB
      filling and emptying time, half of the emptying time, ejection fraction at 30th
      and 60th min) in all patients. RESULTS: We found the sensitivity and specificity
      as 88% and 86% for Clo test and as 89% and 80% for histologic evaluation,
      respectively. The parameters of GB function were not significantly different in H
      pylori positive and negative patients. The GB emptying was normal in both groups.
      Minimum GB filling time was 30 min in 34 of 86 cases (39.5%), filling was not
      observed in 2 cases. The GB ultrasonography (USG) results were normal for all
      cases and bile composition abnormality was not determined. CONCLUSION: Our study
      showed that 14C-UBT is highly reliable method to detect the presence of H pylori.
      The presence of H pylori infection does ot directly affect the GB function.

PMID- 18322957
TI  - Relevance of MUC1 mucin variable number of tandem repeats polymorphism in H
      pylori adhesion to gastric epithelial cells.
AB  - AIM: To evaluate the influence of MUC1 mucin variable number of tandem repeats
      (VNTR) variability on H pylori adhesion to gastric cells. METHODS: Enzyme linked
      immunosorbent assay (ELISA)-based adhesion assays were performed to measure the
      adhesion of different H pylori strains (HP26695 and HPTx30a) to gastric carcinoma
      cell lines (GP202 and MKN45) and GP202 clones expressing recombinant MUC1 with
      different VNTR lengths. RESULTS: Evaluation of adhesion results shows that H
      pylori pathogenic strain HP26695 has a significantly higher (P<0.05) adhesion to
      all the cell lines and clones tested, when compared to the non-pathogenic strain
      HPTx30a. Bacteria showed a significantly higher (P<0.05) adhesion to the GP202
      cell line, when compared to the MKN45 cell line. Furthermore, both strains showed
      a significantly higher (P<0.05) adhesion to GP202 clones with larger MUC1 VNTR
      domains. CONCLUSION: This work shows that MUC1 mucin variability conditions H
      pylori binding to gastric cells. The extent of bacterial adhesion depends on the
      size of the MUC1 VNTR domain. The adhesion is further dependent on bacterial
      pathogenicity and the gastric cell line. MUC1 mucin variability may contribute to
      determine H pylori colonization of the gastric mucosa.

PMID- 18322958
TI  - Fatty liver disease in severe obese patients: diagnostic value of abdominal
      ultrasound.
AB  - AIM: To evaluate the sensitivity and specificity of abdominal ultrasound (US) for
      the diagnosis of hepatic steatosis in severe obese subjects and its relation to
      histological grade of steatosis. METHODS: A consecutive series of obese patients,
      who underwent bariatric surgery from October 2004 to May 2005, was selected.
      Ultrasonography was performed in all patients as part of routine preoperative
      time and an intraoperative wedge biopsy was obtained at the beginning of the
      bariatric surgery. The US and histological findings of steatosis were compared,
      considering histology as the gold standard. RESULTS: The study included 105
      patients. The mean age was 37.2+/-10.6 years and 75.2% were female. The
      histological prevalence of steatosis was 89.5%. The sensitivity and specificity
      of US in the diagnosis of hepatic steatosis were, respectively, 64.9% (95% CI:
      54.9-74.3) and 90.9% (95% CI: 57.1-99.5). The positive predictive value and
      negative predictive value were, respectively, 98.4% (95% CI: 90.2-99.9) and 23.3%
      (95% CI: 12.3-39.0). The presence of steatosis on US was associated to advanced
      grades of steatosis on histology (P=0.016). CONCLUSION: Preoperative abdominal US
      in our series has not shown to be an accurate method for the diagnosis of hepatic
      steatosis in severe obese patients. Until another non-invasive method
      demonstrates better sensitivity and specificity values, histological evaluation
      may be recommended to these patients undergoing bariatric surgery.

PMID- 18322959
TI  - Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in
      diabetic mice with gastroparesis.
AB  - AIM: To investigate the potential therapeutic significance of ghrelin and growth
      hormone releasing peptide 6 (GHRP-6) in diabetic mice with gastric motility
      disorders. METHODS: A diabetic mouse model was established by intraperitoneal
      (ip) injection of alloxan. Diabetic mice were injected ip with ghrelin or GHRP-6
      (20-200 microg/kg), and the effects on gastric emptying were measured after
      intragastric application of phenol red. The effect of atropine, NG-nitro-L
      arginine methyl ester hydrochloride (L-NAME) or D-Lys3-GHRP-6 (a growth hormone
      secretagogue receptor (GHS-R) antagonist) on the gastroprokinetic effect of
      ghrelin or GHRP-6 (100 microg/kg) was also investigated. The effects of ghrelin
      or GHRP-6 (0.01-10 micromol/L) on spontaneous or carbachol-induced contractile
      amplitude were also investigated in vitro, in gastric fundic circular strips
      taken from diabetic mice. The presence of growth hormone secretagogue receptor 1a
      transcripts in the fundic strips of diabetic mice was detected by reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: We established a
      diabetic mouse model with delayed gastric emptying. Ghrelin and GHRP-6
      accelerated gastric emptying in diabetic mice with gastroparesis. In the presence
      of atropine or L-NAME, which delayed gastric emptying, ghrelin and GHRP-6 (100
      microg/kg) failed to accelerate gastric emptying. D-Lys3-GHRP-6 also delayed
      gastric emptying induced by the GHS-R agonist. Ghrelin and GHRP-6 increased the
      carbachol-induced contractile amplitude in gastric fundic strips taken from
      diabetic mice. RT-PCR confirmed the presence of GHS-R mRNA in the strip
      preparations. CONCLUSION: Ghrelin and GHRP-6 increase gastric emptying in
      diabetic mice with gastroparesis, perhaps by activating peripheral cholinergic
      pathways in the enteric nervous system.

PMID- 18322960
TI  - Requirements for transfusion and postoperative outcomes in orthotopic liver
      transplantation: a meta-analysis on aprotinin.
AB  - AIM: To study the effect of aprotinin used in orthotopic liver transplantation
      (OLT) on the intraoperative requirement for blood products and on the incidence
      of laparotomy for bleeding, thrombotic events and mortality. METHODS: A
      systematic review of the literature in the electronic database Medline and the
      Clinic Trials Registry Database was performed. Literature that did not fit our
      study were excluded. Patients in the reviewed studies were divided into two
      groups; one group used aprotinin (aprotinin group) while the other did not
      (control group). The data in the literature that fit our requirements were
      recorded. Weighted mean differences (WMD) in the requirements for blood products
      between the aprotinin group and the control group were tested using a fixed
      effect model. A Z test was performed to examine their reliability; the Fleiss
      method of fixed effect model was used to analyze data on postoperative events,
      and odds ratios (ORs) were tested and merged. RESULTS: Seven citations were
      examined in our study. Among them, a requirement for blood products was reported
      in 4 studies including 321 patients, while postoperative events were reported in
      5 studies including 477 patients. The requirement for red blood cells and fresh
      frozen plasma in the aprotinin group was statistically lower than that in the
      control group (WMD=-1.80 units, 95% CI, -3.38 to -0.22; WMD=-3.99 units, 95% CI, 
      6.47 to -1.50, respectively). However, no significant difference was indicated in
      the incidence of laparotomy for bleeding, thrombotic events and mortality between
      the two groups. Analysis on blood loss, anaphylactic reactions and renal function
      was not performed in this study due to a lack of sufficient information.
      CONCLUSION: Aprotinin can reduce the intraoperative requirement for blood
      products in OLT, and has no significant effect on the incidence of laparotomy for
      bleeding, thrombotic events and mortality.

PMID- 18322961
TI  - Percutaneous cryosurgery for the treatment of hepatic colorectal metastases.
AB  - AIM: To determine the safety and efficacy of efficacy of percutaneous cryosurgery
      for treatment of patients with hepatic colorectal metastases. METHODS: Three
      hundred and twenty-six patients with non-resectable hepatic colorectal metastases
      underwent percutaneous cryosurgery under the guidance of ultrasound or CT. Follow
      up was 1 mo after cryosurgery and then every 4 mo thereafter by assessment of
      tumor markers, liver ultrasonography, and abdominal CT. For lesions suspicious of
      recurrence, a liver biopsy was performed and subsequent repeat cryosurgery was
      given if histology was positive for cancer. RESULTS: All patients underwent a
      total of 526 procedures of cryosurgery. There were 151 patients who underwent
      repeat procedures of cryosurgery for recurrent tumors in the liver and
      extrahepatic places. At 3 mo after cryosurgery, carcinoembryonic antigen (CEA)
      levels in 197 (77.5%) patients who had elevated markers before cryosurgery
      decreased to normal range. Among 280 patients who received CT following-up,
      cryotreated lesions showed complete response (CR) in 41 patients (14.6%), partial
      response (PR) in 115 patients (41.1%), stable disease (SD) in 68 patients (24.3%)
      and progressive disease (PD) in 56 patients (20%). The recurrence rate was 47.2%
      during a median follow-up of 32 mo (range, 7-61). Sixty one percent of the
      recurrences were seen in liver only and 13.9% in liver and extrahepatic areas.
      The recurrence rate at cryotreated site was only 6.4% for all cases. During a
      median follow-up of 36 mo (7-62 mo), the median survival of all patient was 29 mo
      (range 3-62 mo). Overall survival was 78%, 62%, 41%, 34% and 23% at 1, 2, 3, 4
      and 5 years, respectively, after the treatment. Patients with tumor size less
      than 3 cm, tumor in right lobe of liver, lower CEA levels (<100 ng/dL) and post
      cryosurgery TACE had higher survival rate. There was no significant difference in
      terms of survival based on the number of tumors, pre-cryosurgery chemotherapy and
      the timing of the development of metastases (synchronous vs metachronous).
      Patients who underwent 2-3 procedures of cryosurgery had increased survival
      compared to patients who received cryosurgery once only. There was no intra
      cryosurgery mortality. Main adverse effects, such as hepatic bleeding, cryoshock,
      biliary fistula, liver failure, renal insufficiency and liver abscess were only
      observed in 0.3%-1.5% of patients. CONCLUSION: Percutaneous cryosurgery was a
      safe modality for hepatic colorectal metastases. Rather than an alternative to
      resection, this technique should be regarded as a complement to hepatectomy and
      as an additional means of achieving tumor eradication when total excision is not
      possible.

PMID- 18322962
TI  - Activator protein-1 involved in growth inhibition by RASSF1A gene in the human
      gastric carcinoma cell line SGC7901.
AB  - AIM: To investigate the role of Ras association domain family protein 1 isoform A
      (RASSF1A) in gastric tumorigenesis. METHODS: Through over-expression of RASSF1A
      gene in the SGC7901 cell line which was induced by a lipofectamine-mediated gene
      transfer approach. Activator protein-1 (AP-1) DNA binding activity was measured
      by electrophoretic mobility shift assay (EMSA). RESULTS: Compared with the
      control clones, cells over-expressing RASSF1A exhibited significant inhibition of
      cell growth with G1 cell cycle arrest in vitro and in vivo. The over-expression
      of RASSF1A significantly inhibited AP-1 activity in SGC7901 cells (0.981+/-0.011
      vs 0.354+/-0.053, P<0.001). In addition, both Western blot analysis and
      immunocytochemistry demonstrated that RASSF1A down-regulated the expression of c
      Fos (0.975+/-0.02 vs 0.095+/-0.024, P<0.001) but not c-Jun. CONCLUSION: Over
      expression of RASSF1A inhibits the growth of SGC7901 cells by negatively
      regulating the AP-1 activity, the latter in turn negatively signals cell
      proliferation.

PMID- 18322963
TI  - Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases
      and the risk of esophageal squamous cell carcinoma in Gansu Chinese males.
AB  - AIM: To evaluate the association between genetic polymorphisms in CYP2E1, ALDH2
      and ADH1B and the risk of esophageal squamous cell carcinoma (ESCC) in a high
      risk area of Gansu Province, in Chinese males. METHODS: A case-control study was
      conducted to investigate the genetic polymorphisms of these enzymes
      (CYP2E1*c1/*c2, ALDH2*1/*2 and ADH1B *1/*1 genotypes). A total of 80 esophageal
      cancer cases and 480 controls were recruited. RESULTS: Compared with controls,
      cases had a greater prevalence of heavier alcohol consumption (53.8% vs 16.2%)
      and a higher proportion of alcohol drinkers with >30 drink-years (28.8% vs
      13.5%). Heavier alcohol consumption and alcohol drinking with >30 drink-years
      increased the risk of ESCC, with ORs (95% CI) of 3.20 (1.32-9.65) and 1.68 (0.96
      3.21). CYP2E1 (*c1/*c1), ALDH2 (*1/*2) and ADH1B (*1/*1) genotype frequencies
      were higher among patients with squamous cell carcinomas, at a level close to
      statistical significance (P=0.014; P=0.094; P=0.0001 respectively). There were
      synergistic interactions among alcohol drinking and ALDH2, ADH1B and CYP2E1
      genotypes. The risk of the ESCC in moderate-to-heavy drinkers with an inactive
      ALDH2 encoded by ALDH2*1/*2 as well as ADH1B encoded by ADH1B *1/*1 and CYP2E1
      encoded by CYP2E1 *c1/*c1 was higher than that in the never/rare-to-light
      drinkers with an active ALDH2 (*1/*1 genotype) as well as ADH1B (*1/*2+*2/*2) and
      CYP2E1 (*c1/*c2+*c2/*c2) genotypes, with a statistically significant difference;
      ORs (95% CI) of 8.58 (3.28-22.68), 27.12 (8.52-70.19) and 7.64 (2.82-11.31)
      respectively. The risk of the ESCC in moderate-to-heavy drinkers with ALDH2
      (*1/*2) combined the ADH1B (*1/*1) genotype or ALDH2 (*1/*2) combined the CYP2E1
      (*c1/*c1) genotype leads to synergistic interactions, higher than drinkers with
      ALDH2 (*1/*1)+ADH1B (*1/*2+*2/*2), ALDH2 (*1/*1)+CYP2E1 (*c1/*c2+*c2/*c2)
      respectively , ORs (95% CI) of 7.46 (3.28-18.32) and 6.82 (1.44-9.76)
      respectively. Individuals with the ADH1B combined the CYP2E1 genotype showed no
      synergistic interaction. CONCLUSION: In our study, we found that alcohol
      consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important
      risk factors for ESCC, and that there was a synergistic interaction among
      polymorphisms in the CYP2E1, ALDH2 and ADH1B genes and heavy alcohol drinking, in
      Chinese males living in Gansu Province, China.

PMID- 18322964
TI  - Cervical cellulitis and mediastinitis following esophageal perforation: a case
      report.
AB  - Chicken bone is one of the most frequent foreign bodies (FB) associated with
      upper esophageal perforation. Upper digestive tract penetrating FB may lead to
      life threatening complications and requires prompt management. We present the
      case of a 52-year-old man who sustained an upper esophageal perforation
      associated with cervical cellulitis and mediastinitis. Following CT-scan evidence
      of FB penetrating the esophagus, the impacted FB was successfully extracted under
      rigid esophagoscopy. Direct suture was required to close the esophageal
      perforation. Cervical and mediastinal drainage were made immediately. Naso
      gastric tube decompression, broad-spectrum intravenous antibiotics, and
      parenteral hyperalimentation were administered for 10 d postoperatively. An
      esophagogram at d 10 revealed no leak at the repair site, and oral alimentation
      was successfully reinstituted. CONCLUSION: Rigid endoscope management of FB
      esophageal penetration is a simple, safe and effective procedure. Primary
      esophageal repair with drainage of all affected compartments are necessary to
      avoid life-threatening complications.

PMID- 18322965
TI  - A case of multiple intra-abdominal splenosis with computed tomography and
      magnetic resonance imaging correlative findings.
AB  - Hepatic splenosis refers to heterotopic auto-transplantation and implantation of
      splenic tissue resulting from the spillage of cells from the spleen after splenic
      trauma or splenectomy. The true incidence of splenosis is unknown, because this
      entity is usually an incidental finding at surgery. Splenic implants are usually
      multiple, and can be localized anywhere in the peritoneal cavity. Splenic
      implants in the peritoneal cavity may be confused with renal tumors, abdominal
      lymphomas and endometriosis. We describe computed tomography (CT) and magnetic
      resonance imaging (MRI) findings in a rare case of multiple intra-abdominal
      splenosis located along the hepatic surface and adjacent to the upper pole of the
      right kidney, mimicking a renal neoplasm.

PMID- 18322966
TI  - Intrauterine midgut volvulus without malrotation: diagnosis from the 'coffee bean
      sign'.
AB  - Fetal midgut volvulus is quite rare, and most cases are associated with
      abnormalities of intestinal rotation or fixation. We report a case of midgut
      volvulus without malrotation, associated with a meconium pellet, during the
      gestation period. This 2.79 kg, 33-wk infant was born via a spontaneous vaginal
      delivery caused by preterm labor. Prenatal ultrasound showed dilated bowel loops
      with the appearance of a 'coffee bean sign'. This patient had an unusual
      presentation with a distended abdomen showing skin discoloration. An emergency
      laparotomy revealed a midgut volvulus and a twisted small bowel, caused by
      complicated meconium ileus. Such nonspecific prenatal radiological signs and a
      low index of suspicion of a volvulus during gestation might delay appropriate
      surgical management and result in ischemic necrosis of the bowel. Preterm labor,
      specific prenatal sonographic findings (for example, the coffee bean sign) and
      bluish discoloration of the abdominal wall could suggest intrauterine midgut
      volvulus requiring prompt surgical intervention.

PMID- 18322967
TI  - Transanal excision of a malignant fibrous histiocytoma of anal canal: a case
      report and literature review.
AB  - Malignant fibrous histiocytoma, which is composed of spindle-shaped cells
      arranged in a pleomorphic and storiform pattern, is rarely found in the
      colorectum. Although complete surgical excision remains the main stem of therapy,
      an optimal treatment strategy according to the stage has not been elucidated. We
      report a case of a 63-year-old woman with an ulcerative lesion in the anorectal
      junction and a final diagnosis of malignant fibrous histiocytoma. We introduced
      an access for transanal local excision and adjuvant radiotherapy because the
      patient refused abdominoperineal resection. No local recurrences or distant
      metastases were observed 15 mo after the operation. To our knowledge, this is the
      first case reported in the English literature of a malignant fibrous histiocytoma
      treated with the transanal local excision and adjuvant radiotherapy. This report
      showed that this approach is selectively reserved for early-stage malignant
      fibrous histiocytoma and for those patients who refuse radical surgery because of
      the risk in a permanent colostomy.

PMID- 18322968
TI  - Overlap of reflux and eosinophilic esophagitis in two patients requiring
      different therapies: a review of the literature.
AB  - Eosinophilic esophagitis (EE) and gastroesophageal reflux disease (GERD) have
      overlapping clinical, manometric, endoscopic and histopathologic features. The
      diagnosis of EE is nowadays based upon the presence of 15 or more eosinophils per
      high power field (eo/HPF) in esophageal biopsies. We report the cases of two
      young males suffering from dysphagia and recurrent food impaction with reflux
      esophagitis and more than 20 eo/HPF in upper-mid esophagus biopsies, both of
      which became asymptomatic on proton pump inhibitor (PPI) therapy. The first
      patient also achieved a histologic response, while EE remained in the other
      patient after effective PPI treatment, as shown by 24-h esophageal pH monitoring.
      Topical steroid therapy combined with PPI led to complete remission in this
      latter patient. GERD and EE may be undistinguishable, even by histology, so
      diagnosis of EE should only be established after a careful correlation of
      clinical, endoscopic and pathologic data obtained under vigorous acid
      suppression. These diagnostic difficulties are maximal when both diseases
      overlap. Limited data are available about this topic, and the interaction between
      EE and GERD is a matter of debate. In this setting, upper-mid esophagus step
      biopsies and esophageal pH monitoring of patients on PPI therapy are pivotal to
      evaluate the role of each disease. A PPI trial is mandatory in patients with a
      histopathologic diagnosis of EE; in those unresponsive to PPI treatment, EE
      should be suggested. However, a clinical response to PPI may not rule out
      quiescent EE, as shown in this report.

PMID- 18322969
TI  - Complications of extrahepatic echinococcosis: fistulization of an adrenal hydatid
      cyst into the intestine.
AB  - Echinococcal cysts are usually found in liver and lungs, but any other organ can
      potentially be involved. Extrahepatic disease due to hydatid cyst may develop in
      the abdominal and pelvic cavity, aside from in other less common locations, which
      may make both diagnosis and treatment more complex. We present a rare case of
      extrahepatic echinococcosis in a 70-year old patient with a 4-d history of dull
      abdominal pain, anemia within the transfusion range and fever. She underwent
      surgery for left renal hydatid cysts 30 years ago. After non operative treatment,
      imaging studies showed a calcified hydatid cyst in a retrogastric location
      communicating with a proximal jejunal loop. En-block resection of the mass
      together with the adrenal gland was performed including closure of the enteric
      fistula. Anatomic pathology confirmed the diagnosis of a calcified hydatid cyst
      of left adrenal origin. Surgery is the treatment of choice and most authors
      recommend removal of cyst and adrenal gland.

PMID- 18322970
TI  - Methotrexate therapy for psoriatic arthritis: reappraisal of an old remedy.

PMID- 18322971
TI  - Lessons from magnetic resonance imaging studies in rheumatoid arthritis.

PMID- 18322972
TI  - Infections, drugs, and rheumatoid arthritis. What have we learned?

PMID- 18322973
TI  - Diffuse idiopathic skeletal hyperostosis: time for a change.

PMID- 18322974
TI  - IgM-rheumatoid factor, anti-cyclic citrullinated peptide, and anti-citrullinated
      human fibrinogen antibodies decrease during treatment with the tumor necrosis
      factor blocker infliximab in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the effect of treatment with infliximab on serum levels
      of rheumatoid factor (IgM-RF), antibodies against cyclic citrullinated peptide
      (anti-CCP), and antibodies against deiminated human fibrinogen, a specific
      citrullinated peptide (ACF), and their association with disease activity and
      disease duration in patients with rheumatoid arthritis (RA). METHODS: The study
      sample included 62 consecutive patients who were treated with infliximab for at
      least one year. IgM-RF, anti-CCP, and ACF were measured at 0, 14, 30, and 46
      weeks. RESULTS: Patients had a mean age of 54 years and median disease duration
      of 10 years and were predominantly female (81%). At baseline 63%, 77%, and 82% of
      patients were positive for IgM-RF, anti-CCP, and ACF, respectively. In terms of
      percentages, the levels of IgM-RF were reduced by 64% at 46 weeks, while anti-CCP
      and ACF levels were reduced by roughly 25%. The decrease in serum levels of these
      autoantibodies was not associated with the decrease in disease activity. The
      change in ACF was significantly related to disease duration, while the changes in
      IgM-RF or anti-CCP were not. CONCLUSION: In a cohort of patients with RA who
      responded to infliximab therapy, all autoantibodies decreased significantly, but
      IgM-RF showed a larger decrease than anti-CCP or ACF. These changes in levels of
      autoantibodies are not directly related to the change in disease activity. Early
      in the disease, ACF levels were best influenced by treatment with infliximab.

PMID- 18322975
TI  - Ossification of the posterior longitudinal ligament.

PMID- 18322976
TI  - Bone marrow histology in a patient with fever of unknown origin.

PMID- 18322977
TI  - Systemic nocardiosis in a case of rheumatoid arthritis treated with tumor
      necrosis factor blockers.

PMID- 18322979
TI  - Intrinsic muscle spasm of the hand: Bunnell's sign.

PMID- 18322980
TI  - Nocardia infection with adalimumab in rheumatoid arthritis.

PMID- 18322981
TI  - Prevalence of patello- and tibiofemoral osteoarthritis in Elva, Southern Estonia.

PMID- 18322982
TI  - Rapid response of nail psoriasis to etanercept.

PMID- 18322983
TI  - Morphology and phenotype expression of types I, II, III, and X collagen and MMP
      13 of chondrocytes cultured from articular cartilage of Kashin-Beck Disease.
AB  - OBJECTIVE: We investigated the characteristics of cell morphology and expression
      of types I, II, III, and X collagen and matrix metalloproteinase-13 (MMP-13) of
      chondrocytes from articular cartilage of adult patients with Kashin-Beck Disease
      (KBD) in vitro to understand the pathogenesis in chondrocytes. METHODS: Samples
      of articular cartilage were divided into 2 groups: KBD group (8 samples, 8 cases)
      and the control (8 samples, 8 cases). KBD patients were diagnosed according to
      "Pathological Criteria to Diagnose KBD in China." Hyaline cartilage was digested
      with collagenase into cell suspensions and cultured in monolayers. Chondrocyte
      ultrastructure was observed by electron microscope at 10th day in vitro. Primary
      articular chondrocytes were seeded on microscope slides and immunostained on 12th
      day of cultivation for types I, II, III, and X collagens and MMP-13. Positive
      findings were counted by light microscopy and confirmed by flow cytometric
      analyses. RESULTS: Considerable amounts of vacuoles and distorted nuclei, as well
      as thickening and irregular arrangement of collagen fibrils, were seen in the KBD
      samples by electron microscopy. Types I, III, and X collagen were stained in the
      KBD, but not in the control cultures. The percentages of positive staining for
      type II collagen were significantly lower in KBD than those in controls (t col II
      = -5.54, p < 0.001), and for MMP-13 in the KBD group were significantly higher (t
      MMP-13 = 3.70, p < 0.01). CONCLUSION: Phenotype expressions of types I, II, III,
      and X collagen and MMP-13 in chondrocytes cultured in vitro were significantly
      different between the KBD and control cultures, indicating degenerative and
      hypertrophic changes in chondrocytes of KBD articular cartilage.

PMID- 18322984
TI  - Autoantibody to signal recognition particle in African American girls with
      juvenile polymyositis.
AB  - Anti-signal recognition particle (anti-SRP) is a myositis-specific autoantibody
      that is linked to a severe polymyositis (PM) associated with interstitial lung
      disease (ILD) and esophageal dysmotility in adults. We describe 3 African
      American adolescent girls with anti-SRP juvenile PM. One child required
      aggressive treatment to control her disease and 2 were refractory to multiple
      immunosuppressants. Patient 1 developed ILD and cardiac disease; Patient 2
      developed ILD; Patient 3 developed esophageal dysmotility and cardiac disease.
      Organ system involvement was comparable to that seen in adults. We conclude that
      testing for anti-SRP in children with PM may facilitate diagnosis and management.

PMID- 18322985
TI  - Localized scleroderma severity index and global assessments: a pilot study of
      outcome instruments.
AB  - OBJECTIVE: To develop a disease outcome instrument measuring localized
      scleroderma (LS) severity and to determine its reliability. METHODS: Patients
      with LS were evaluated by 2 rheumatologists. The LS Severity Index (LoSSI)
      comprises the sum of 4 clinical skin scores measured at 14 cutaneous anatomic
      sites: extent of surface area (SA) affected, erythema score (ES), skin thickness
      (ST) score, and new lesion/extension (N/E). Physician and patient global
      assessments (GA) were recorded on a 100 mm visual analog scale. RESULTS: Twenty
      two patients with LS had 66 visits, during which 91 lesions were assessed.
      Individual skin scores (SA, ES, ST) and LoSSI showed substantial interrater
      reliability (kappaw 0.77-0.83; percentage agreement 93.41%-96.70%). Intrarater
      variability was calculated using 26 anatomic sites and 9 pair-visits. Each skin
      score demonstrated excellent reliability (kappaw 0.56-0.80, percentage agreement
      90.39%-94.23%). Physician GA showed substantial interrater correlation [0.72, 95%
      confidence interval (CI) 0.57, 0.87]. There was only fair correlation between
      physician and patient GA (0.27, 95% CI 0.00, 0.64). The standardized response
      means for LoSSI and physician GA were large (1.86 and 2.55) for those who
      improved after therapy. CONCLUSION: LS clinical trials are impeded by the lack of
      reliable and reproducible outcome measures. We have developed the LoSSI to
      correct this deficiency. Our pilot study demonstrates that the LoSSI is reliable
      and reproducible in measuring LS severity and therapeutic effects and can be
      easily implemented into the clinical examination of patients with LS. Both LoSSI
      and physician GA were sensitive to clinical changes in patients with LS. A formal
      study should be conducted to validate these preliminary findings.

PMID- 18322986
TI  - Elevation of serum lymphotactin levels in patients with systemic sclerosis.
AB  - OBJECTIVE: To determine serum concentrations of lymphotactin, a Th1 chemokine,
      and their clinical association in patients with systemic sclerosis (SSc).
      METHODS: Lymphotactin levels were examined in serum samples from patients with
      SSc (n = 68), systemic lupus erythematosus (SLE; n = 42), or dermatomyositis (DM;
      n = 29), and healthy controls (n = 18) by enzyme linked immunosorbent assay.
      RESULTS: Serum lymphotactin levels were significantly elevated in SSc patients
      compared to patients with SLE or DM as well as controls. Serum lymphotactin
      levels were similar in patients with limited cutaneous SSc and diffuse cutaneous
      SSc (dSSc). Clinical correlation of elevated lymphotactin levels was not detected
      in the total group of patients with SSc, while elevation of lymphotactin levels
      was significantly associated with higher percentage vital capacity and percentage
      diffusing capacity of carbon monoxide, lower lung severity grade and serum IgG
      levels, and less frequent presence of short sublingual frenulum in patients with
      dSSc. CONCLUSION: Our results indicate that elevated serum lymphotactin levels
      correlate with relatively milder manifestations in dSSc, especially lower
      severity of lung involvement, suggesting that lymphotactin may play a role in the
      development of dSSc.

PMID- 18322987
TI  - Minimal clinically important difference for 7 measures of fatigue in patients
      with systemic lupus erythematosus.
AB  - OBJECTIVE: To determine the minimal clinically important difference (MCID) for 7
      measures of fatigue in patients with systemic lupus erythematosus (SLE). METHODS:
      Study subjects completed 7 fatigue instruments [Fatigue Severity Scale (FSS),
      Multidimensional Assessment of Fatigue (MAF), Multidimensional Fatigue Inventory
      (MFI), Vitality scale of the MOS-SF-36, Chalder Fatigue Scale (CFS), Functional
      Assessment of Chronic Illness Therapy-Fatigue, and a global Rating Scale (RS)]
      and then participated in a series of interviews with other study participants
      comparing their fatigue with one another. Each interview participant rated the
      difference in their fatigue levels on a 7-point transition scale. The MCID was
      estimated from the mean difference in fatigue scores between each pair of
      interview participants based on their subjective rating of fatigue contrast. The
      MCID was also estimated using linear regression modeling. RESULTS: Eighty
      patients with SLE participated. Patients reported significant levels of fatigue
      [mean normalized (0 = none, 100 = maximum) fatigue scores for the 7 instruments
      ranged from 49.8 (CFS) to 71.1 (FSS)]. The MCID of "a little more" fatigue tended
      to be greater than the MCID for a "little less fatigue" and differed
      significantly for FSS and MAF. The MCID of normalized scores estimated by linear
      regression ranged from 7.0 (CFS) to 14.3 (MFI). CONCLUSION: Fatigue is a common
      and debilitating component of SLE. Estimates of MCID will help to interpret
      changes observed in a fatigue score and will be critical in estimating sample
      size requirements for clinical trials including fatigue as an outcome.

PMID- 18322988
TI  - A personality characteristic, somatic absorption, and the perception of somatic
      symptoms in rheumatoid arthritis patients.
AB  - OBJECTIVE: This study tested the hypothesis that a personality trait, somatic
      absorption, is correlated with symptom severity in patients with rheumatoid
      arthritis (RA). METHODS: Patients completed self-report questionnaires assessing
      intensity of their RA symptoms, somatic absorption, and psychiatric distress.
      Disease activity and severity were measured through erythrocyte sedimentation
      rate, joint examination, and aggressiveness of medication regimen. We examined
      the cross-sectional association between somatic absorption and RA symptoms using
      multivariable regression analyses. RESULTS: Somatic absorption was significantly
      (p < 0.05) associated with an overall measure of RA symptoms, and this
      association persisted after taking into account demographic data, disease
      severity, and extent of psychological distress. Somatic absorption was more
      closely associated with constitutional symptoms than with localized, articular
      symptoms of arthritis. Somatic symptoms were also independently associated with
      psychiatric distress (p < 0.001). Psychiatric distress was a more powerful
      predictor of extraarticular or constitutional symptoms than were measures of
      arthritis activity and severity. CONCLUSION: Our findings suggest that there may
      be a role for psychological intervention in the management of extraarticular
      symptoms of RA as these symptoms are relatively more influenced by a personality
      characteristic than the localized articular symptoms of the disease.

PMID- 18322989
TI  - Comparison of internal and external responsiveness of the generic Medical Outcome
      Study Short Form-36 (SF-36) with disease-specific measures in rheumatoid
      arthritis.
AB  - OBJECTIVE: To examine the comparative internal and external responsiveness of the
      generic Medical Outcome Study Short Form-36 Health Survey (SF-36) and disease
      specific measures in patients with rheumatoid arthritis (RA). METHODS: Data were
      collected from 280 RA patients starting anti-tumor necrosis factor treatment. A
      total of 168 patients completed a questionnaire including the SF-36, the
      Arthritis Impact Measurement Scales 2 (AIMS2), the Health Assessment
      Questionnaire (HAQ), a visual analog scale for general health (VAS-GH), and an 11
      point numerical rating scale for pain (NRS pain) at baseline and after 12 months.
      Internal responsiveness was evaluated with paired samples t-tests and
      standardized response means (SRM). External responsiveness was investigated with
      receiver-operating characteristic statistics and Spearman rank-order correlation
      coefficients. A health transition item was used as the external indicator of
      change. RESULTS: No significant differences in internal and external
      responsiveness were found between the SF-36 and disease-specific measures within
      the domains physical function, pain, and psychological function. In the domain
      social function, the SF-36 was more responsive than the AIMS2. In the domain
      general health, the SF-36 was less responsive (only internal) than the AIMS2 and
      VAS-GH. CONCLUSION: Our study showed comparable internal and external
      responsiveness of the SF-36 compared with disease-specific measures (AIMS2, HAQ,
      NRS pain) in all health domains, except social function and general health
      domains. The assumption that disease-specific measures are more responsive to
      detect intervention-related changes over time is not confirmed by our data.

PMID- 18322990
TI  - Comparison of an in vitro tuberculosis interferon-gamma assay with delayed-type
      hypersensitivity testing for detection of latent Mycobacterium tuberculosis: a
      pilot study in rheumatoid arthritis.
AB  - OBJECTIVE: Recommendations for screening for latent Mycobacterium tuberculosis
      (MTB) infection have been proposed but are not well studied in patients with
      rheumatoid arthritis (RA). We estimated the prevalence of anergy in RA and
      evaluated different methods to detect MTB exposure. METHODS: This was a
      prospective pilot study of 61 patients with RA and 42 healthy controls.
      Tuberculin skin test (TST) antigen, Candida, and tetanus toxoid were injected
      intradermally using the Mantoux method. Subjects negative for TST returned for a
      second-step test. Whole-blood interferon-gamma (IFN-gamma) release to
      mycobacterial antigens was evaluated with the first-generation QuantiFeron test
      (QIFN). RESULTS: Cutaneous anergy in patients with RA was not significantly
      different than healthy controls (p = 0.154), and was not affected by disease
      modifying antirheumatic drugs (p = 0.270). In patients with RA, 16.4% had
      positive TST with 10 mm cutoff vs 11.9% of controls. Using a 5 mm cutoff, 21.3%
      of patients with RA were positive, and this increased to 29.5% with a second-step
      TST. QIFN detected MTB exposure in 18% of patients with RA and 19% of controls (p
      = 0.897). However, indeterminate QIFN tests were higher in RA patients (11.5%)
      compared to controls (2.4%), demonstrating a lower sensitivity to detect latent
      MTB. CONCLUSION: Cutaneous anergy may be less common than previously reported in
      patients with RA. patients. However, the single-step TST and 10 mm cutoff may
      fail to detect all cases of latent exposure in RA patients. High rates of
      indeterminate results in QIFN testing suggest that QIFN should not be employed as
      an alternative, single-screening test in patients with RA. These pilot results
      require confirmation in larger studies to determine the optimal screening
      strategy in RA.

PMID- 18322991
TI  - Clinical outcome and imaging changes after intraarticular (IA) application of
      etanercept or methylprednisolone in rheumatoid arthritis: magnetic resonance
      imaging and ultrasound-Doppler show no effect of IA injections in the wrist after
      4 weeks.
AB  - OBJECTIVE: To assess the magnetic resonance imaging (MRI) and ultrasound (US)
      changes in the wrist of patients with rheumatoid arthritis (RA) 4 weeks after an
      US guided intraarticular (IA) injection. METHODS: Contrast enhanced MRI and US
      Doppler were performed at baseline and 4 weeks after IA injection of either 40 mg
      methylprednisolone (n = 12) or 25 mg etanercept (n = 13) in 25 patients with RA
      taking disease modifying antirheumatic drugs with a therapy-resistant wrist
      joint. All injections were US guided. RESULTS: There was an improvement in
      swollen target joint score (p < 0.001), tender target joint score (p < 0.002),
      and physician visual analog scale score (p < 0.001) after 4 weeks. Baseline MRI
      synovitis score was mean 5.08 (range 3-9) and was unchanged at followup in the
      whole group (p = 0.52) and between treatment groups (p = 0.43). MRI edema score
      (mean 4.46, range 0-29) in the total group was unchanged after 4 weeks (p =
      0.13), whereas MRI erosion score increased in the total group from baseline,
      17.88 (range 7-40), to 4 weeks, 18.25 (range 7-40) (p < 0.001). Neither US
      Doppler color fraction (0.07) nor Resistive Index (RI) (p = 0.36) changed from
      baseline to 4 week followup. CONCLUSION: In contrast to the clinical evaluation,
      imaging measures of relevance for the estimation of inflammation, US-Doppler, US
      RI, MRI synovitis, and bone-marrow edema did not change 4 weeks after a single IA
      injection of either methylprednisolone or etanercept in the wrist. Within the
      same period, erosive progression in some patients suggested that joints with
      active disease may deteriorate within as little as 1 month, and that this
      development is not arrested by 1 injection. Given the small sample size of our
      study further studies are required to confirm our results.

PMID- 18322992
TI  - Serum amyloid A activates nuclear factor-kappaB in rheumatoid synovial
      fibroblasts through binding to receptor of advanced glycation end-products.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, symmetric polyarticular joint
      disease and serum amyloid A (SAA) is an acute-phase protein that is upregulated
      during the course of RA. We investigated the role of SAA in the pathogenesis of
      RA. METHODS: Fibroblast-like synovial cells (FLS) were established from RA
      joints. SAA-stimulated expression of cytokines from FLS was evaluated by ELISA.
      Nuclear factor-kappaB (NF-kappaB) activation by SAA was evaluated by luciferase
      assay. NF-kappaB activation and IkappaBalpha degradation were evaluated by
      Western blotting and nuclear localization of p65 subunit of NF-kappaB in FLS.
      Expression of receptor for advanced glycation end-products (RAGE) in synovial
      tissue was evaluated by immunohistochemical study. Effects of preincubation of
      soluble RAGE on NF-kappaB activation by SAA was evaluated by Western blotting of
      IkappaBalpha. RESULTS: SAA stimulated the transcriptional activation by NF-kappaB
      in a dose-dependent manner and induced expression of the proinflammatory
      cytokines interleukin 6 (IL-6) and IL-8. Higher expression of RAGE in synovial
      tissue from patients with RA was noted. SAA induced IkappaBalpha degradation,
      with the peak effect around 30 minutes. Preincubation of SAA with soluble
      recombinant RAGE protein prevented SAA-induced IkappaBalpha degradation. SAA
      stimulation promoted nuclear translocation of NF-kappaB, whereas preincubation of
      SAA with RAGE inhibited nuclear translocation. CONCLUSION: Our data suggested
      that the SAA-RAGE-stimulated NF-kappaB signaling pathway has an important role in
      the pathogenesis of RA.

PMID- 18322993
TI  - Time to score quantitative rheumatoid arthritis measures: 28-Joint Count, Disease
      Activity Score, Health Assessment Questionnaire (HAQ), Multidimensional HAQ
      (MDHAQ), and Routine Assessment of Patient Index Data (RAPID) scores.
AB  - OBJECTIVE: To analyze the time required to score different measures used to
      assess patients with rheumatoid arthritis (RA), as a guide to feasibility in
      standard care. The measures studied were a 28-Joint Count, Disease Activity Score
      (DAS), Health Assessment Questionnaire (HAQ), Multidimensional HAQ (MDHAQ), and
      various Routine Assessment of Patient Index Data (RAPID) scores derived from the
      MDHAQ. METHODS: Three rheumatologists at 3 sites performed and timed 28-joint
      counts in 20 different patients at each site. Each rheumatologist scored and
      timed identical data in 5 groups of 10 from the same 50 patients seen in standard
      clinical care, including 50 DAS28 indices using the DAS Website, 50 identical
      HAQ, and 50 identical MDHAQ from the same patients. The MDHAQ includes 10
      activities self-assessed for physical function, 21 circle visual analog scales
      (VAS) (rather than 10 cm lines), and scoring templates on the questionnaire for
      physical function, patient self-report joint count and RAPID composite scores.
      RAPID3 includes the 3 Core Data Set measures, RAPID4 adds the self-report joint
      count to RAPID3, and RAPID5 adds a physician global estimate to RAPID4. RESULTS:
      The median number of seconds to complete a 28-joint count was 90, compared to
      41.9 s for a HAQ, 9.6 s for an MDHAQ RAPID3, and 19.4 s for RAPID5. CONCLUSION:
      MDHAQ RAPID3 scores can be calculated in considerably less time than other RA
      measures, using scoring templates on the MDHAQ, to provide informative, feasible,
      quantitative measures for standard rheumatology clinical care.

PMID- 18322994
TI  - Common polymorphisms in the folate pathway predict efficacy of combination
      regimens containing methotrexate and sulfasalazine in early rheumatoid arthritis.
AB  - OBJECTIVE: To study genetic polymorphisms in the folate pathway, a site of action
      of methotrexate (MTX) and sulfasalazine (SSZ), as predictors of efficacy of
      combination disease modifying antirheumatic drug (DMARD) regimens containing MTX
      and SSZ in early rheumatoid arthritis (RA). METHODS: Ninety-eight Caucasian
      patients with early RA received MTX with SSZ, hydroxychloroquine, and folate
      according to a standardized protocol. Efficacy was evaluated using the Disease
      Activity Score (DAS28) and European League Against Rheumatism response criteria
      at 12 months. Nine polymorphisms in 7 genes of the folate pathway were studied.
      RESULTS: Response to therapy was associated with SLC19A1, MTR, and TYMS
      polymorphisms. Two favorable allele combinations associated with responder status
      at 12 months were identified: the MTR 2756A allele in combination with either the
      SLC19A1 80A allele or the TYMS 3R-del6 haplotype (multivariate analysis, p =
      0.0002, p = 0.009 respectively). Seventy of the 72 patients with these allele
      combinations responded compared to 12/24 patients without [odds ratio (OR) 35.0,
      95% confidence interval (CI) 6.9-176, p < 0.0001]. An association with remission
      (DAS28 < 2.6) was also observed (OR 3.4, 95% CI 1.1-10.0, p = 0.04). When
      analyzed over 3 years, both the change in DAS score from baseline and the final
      DAS scores were significantly higher and lower, respectively, with the favorable
      genotype group (p < 0.0001, p < 0.0001). CONCLUSION: Polymorphic variations in
      the MTR, SLC19A1, and TYMS genes were associated with better clinical response to
      combination DMARD regimens containing MTX and SSZ. Allele combinations of these
      genes may predict response to combination DMARD and assist in treatment decisions
      in patients with early RA.

PMID- 18322995
TI  - Using extremity magnetic resonance imaging to assess and monitor early rheumatoid
      arthritis: the optimal joint combination to be scanned in clinical practice.
AB  - OBJECTIVE: To identify the optimal combination for detecting erosions in early
      rheumatoid arthritis using extremity magnetic resonance imaging (eMRI). METHODS:
      In 44 patients, eMRI of 1 hand identified 77% who were erosive, 2 hands 89%, and
      2 hands and feet 91%. RESULTS: eMRI identified 4 times as many erosions as
      radiography. At 6 months, eMRI of 1 hand identified an increase in erosions in
      50% subjects, 2 hands in 55%, and 2 hands and feet in 55%. When only subjects
      with a change in erosion score above the smallest detectable difference were
      considered, these numbers were 30%, 25%, and 20%, respectively. CONCLUSION: eMRI
      provides superior erosion identification compared to radiography. Imaging 2 hands
      can be used as a screening tool and 1 hand to monitor erosions over time.

PMID- 18322996
TI  - [Symposium on cancer of the cervix].

PMID- 18322997
TI  - The Horn-Hellersberg test: responses of three to eleven year old children.

PMID- 18322998
TI  - The Case of Gregor: interpretation of test data. Symposium presented at American
      Psychological Association Meeting, Denver, 1949.

PMID- 18322999
TI  - The Thompson modification of the thematic apperception test.

PMID- 18323000
TI  - The interpersonal equation in projective methods.

PMID- 18323001
TI  - Lymphomata (including Hodgkin's-like sarcomata): their experimental production. A
      study of their pathogenesis and etiology and a comparison with corresponding
      tumours in man.

PMID- 18323002
TI  - The extrahepatic biliary system. Its phylogeny.

PMID- 18323003
TI  - Anti-HIV agents. Viral load blips linked to adherence.

PMID- 18323004
TI  - [Follow-up and orientation of pregnant women regarding identified risk
      situations. Professional guidelines: a synthesis (May 2007)].

PMID- 18323005
TI  - The Finnish Heart Association. Interview by Robert Short.

PMID- 18323006
TI  - [Commentary on a case of Heyde's syndrome].

PMID- 18323007
TI  - Characteristic electron microscopic findings in the skin of patients with
      fibromyalgia--preliminary study.
AB  - This blinded study was done to determine if there are any abnormal electron
      microscopic (EM) findings in the skin of fibromyalgia syndrome (FMS) patients,
      which might contribute to or be due to the increased pain sensitivity seen in
      this condition. Skin biopsy samples were obtained from 13FMS patients and 5
      control subjects. All tissues were prepared for EM examination by immediate
      prefixation in 2.5% glutaraldehyde for 2 h and postfixation in 1% osmium acid for
      24 h. Ultrathin sections on grids were stained by uranylacetate and lead citrate.
      Biopsies were read by an individual without knowledge of participant status. Five
      skin biopsies from healthy controls showed relatively even distribution of
      variegated sized unmyelinated axons sheathed well by complicatedly folded Schwann
      cell membranes. In tissues from 9/13 FMS patients, unmyelinated Schwann cells
      were noted to be ballooned, whereas this finding was not noted in any controls
      (p=0.029). Axons in most patients trended towards being localized in the
      periphery of the unmyelinated Schwann cell sheaths (p=0.002). Particularly,
      peripheral localization of axon in the unmyelinated Schwann cell sheath had a
      strong relationship with ballooning of Schwann cell (p=0.042), simplified folding
      of Schwann cell sheath (p=0.039) and smaller axon (p=0.034). Myelinated nerve
      fibers were unremarkable. The EM findings seen in the skin of FMS patients show
      unusual patterns of unmyelinated nerve fibers as well as associated Schwann
      cells. If these findings are replicated in a larger study, these abnormalities
      may contribute to, or be due to, the lower pain threshold seen in FMS patients.

PMID- 18323008
TI  - Let the data flow!

PMID- 18323009
TI  - Accuracy of IgE antibody laboratory results.

PMID- 18323010
TI  - [Hirsutism].

PMID- 18323011
TI  - ['Neurodevelopmental treatment' following stroke: no beneficial effect shown in
      measurements taken after 1 year; comparative study].

PMID- 18323012
TI  - [Basis of clinical economics (6)].

PMID- 18323013
TI  - [Health and welfare of the aged (4): "Campaign to improve oral function"].

PMID- 18323014
TI  - Applauds changes to JAVMA and addition to staff.

PMID- 18323015
TI  - Teaching resources. Using web-based discussion forums as a model of the peer
      review process and a tool for assessment.
AB  - This Teaching Resource describes how to use an online asynchronous discussion as
      a mechanism to introduce students to the peer-review process, as well as to
      assess student performance and understanding. This method was applied to a
      graduate course on signal transduction and the Teaching Resource includes a
      syllabus, detailed plan for incorporating the online discussion, sample journal
      club questions, and sample student responses to the discussion forum, faculty
      responses, and student revisions.

PMID- 18323017
TI  - Uniform myosin isoforms in the flight muscles for little brown bats, Myotis
      lucifugus.
AB  - The present study used muscle histochemistry and polyacrylamide gel
      electrophoresis of native myosin and myosin heavy chains to establish a
      correlation, if any, between chiropteran histochemical fiber types and myosin
      isoform composition. Histochemical analysis of the primary flight muscle, the
      pectoralis profundus, documented the presence of a single histochemical fiber
      type, here termed Type II. Electrophoresis of native myosin isolated from
      pectoralis muscle yielded a single isoform that comigrated with the FM-3 isoform
      of rat diaphragm. Heavy chain analysis of the Myotis pectoralis demonstrated a
      single heavy chain with comparable electrophoretic mobility to rat IIa myosin
      heavy chain. These data demonstrate unique histochemical and biochemical
      homogeneity in the myosin composition of the pectoralis muscle of Myotis
      lucifugus. Thus this muscle is extremely specialized for flight at histochemical,
      morphologic, and molecular levels. These data contrast with the mixed myosin and
      histochemical fiber types found in other mammals, as well as in other muscles of
      Myotis lucifugus.

PMID- 18323018
TI  - [The inhabitants of Lendava according to population registers, 1909-19].

PMID- 18323016
TI  - The sodium pump alpha1 subunit as a potential target to combat apoptosis
      resistant glioblastomas.
AB  - PURPOSE: To review the involvement of the ion transporter Na+/K+-ATPase (NaK) in
      the migration and proliferation of glioma cells. Preliminary studies indicate
      that NaK alpha1 subunits seem to be upregulated in a proportion of glioblastomas
      but not in normal brain tissues. DESIGN: The present review focuses on (1) the
      natural resistance of migrating malignant glioma cells to apoptosis, (2)
      autophagic cell death as an alternative to combat malignant gliomas, (3) the fact
      that reducing the levels of malignant glioma cell motility can restore
      proapoptotic drug sensitivity,and (4) on the observation that inhibiting the NaK
      activity reduces both glioma cell proliferation and migration. RESULTS: The
      natural ligands of the NaK are the cardiotonic steroids. A hemisynthetic
      derivative of 2"-oxovoruscharin (UNBS1450), a novel cardenolide, displays unique
      structural features, making its binding affinity to NaK alpha subunits (including
      alpha1) 10 to 100 times higher than that of other cardenolides. UNBS1450 markedly
      decreases intracellular ATP concentration in glioma cells, disorganizes the actin
      cytoskeleton, and leads to autophagic cell death in NaK alpha1 over-expressing
      glioma cells. CONCLUSIONS: Glioblastoma patients who do not respond to
      chemotherapy and whose tumors over-express NaK alpha1 subunits could benefit from
      a treatment using ligands with marked binding affinity for the NaK alpha1
      subunit.

PMID- 18323019
TI  - Sex and soldiering in France and Flanders: the British Expeditionary Force along
      the western front, 1914-1919.

PMID- 18323020
TI  - Abstracts of the 10th International Congress of Therapeutic Drug Monitoring and
      Clinical Toxicology. September 9-14, 2007. NIce, France.

PMID- 18323021
TI  - Metabolic syndrome and the onset of cancer. Proceedings of the 8th Postgraduate
      Nutrition Symposium. March 15-16, 2006. Boston, Massachusetts, USA.

PMID- 18323022
TI  - Counting difficulties: retained instruments, sponges, and needles.
AB  - Patients in whom a sponge or instruments is left after surgery may suffer
      complications including pain, infection, abscess, or intestinal obstruction.
      Consequences or retained items for surgical team members may include malpractice
      lawsuits and adverse actions from the National Practitioner Data Bank and state
      licensing board. Adherence to AORN recommended practices for counting and
      facility counting policies can protect both patients and practitioners.

PMID- 18323023
TI  - Trauma: when there's no time to count.
AB  - Trauma is the leading cause of death for people younger than age 45 in the United
      States. To help prevent death or disability, critically injured trauma patients
      must reach definitive care within the "golden hour."Often, the perioperative team
      has no more than 10 minutes to prepare the room before a patient who has suffered
      multiple, critical, traumatic injuries is rushed into the OR. For the trauma
      patient's safety, the perioperative team must be diligent and use creative
      measures to efficiently ensure that all surgical counts are completed. Foregoing
      surgical counts places the trauma patient at an increased risk for
      unintentionally retained foreign objects.

PMID- 18323024
TI  - Improving compliance with Occupational Safety and Health Administration
      standards.
AB  - Health care facilities can be dangerous places. The mission of the Occupational
      Safety and Health Administration (OSHA) is to improve the safety of the American
      workplace by developing and implementing standards that prevent occupational
      injury, illness, and death. Perioperative services are performed in environments
      where exposure to bloodborne pathogens is a daily occurrence, making
      implementation and compliance with OSHA standards very important. Employees and
      employers must remain current with workplace safety requirements, including use
      of personal protective equipment. This article presents implications of the OSHA
      standards for employers, educators, and employees.

PMID- 18323025
TI  - [The forgotten victims of torture of World War I: the "pithiatics"].

PMID- 18323026
TI  - The melting drape.

PMID- 18323027
TI  - "Those miserable Tommies": anti-British sentiment in the Australian Imperial
      Force, 1915-1918.

PMID- 18323028
TI  - The limits of maternalism: gender ideology and the south German Catholic working
      women's associations, 1904-1918.

PMID- 18323029
TI  - The unknown sock knitter: voluntary work, emotional labour, bereavement and the
      Great War.

PMID- 18323030
TI  - Bibliography. Current world literature. Nutrition.

PMID- 18323031
TI  - All the feelings that are fit to print: the community of sentiment and the
      literary public sphere in China, 1900-1918.

PMID- 18323032
TI  - The hidden history of refugee schooling in Britain: the case of the Belgians,
      1914-18.

PMID- 18323033
TI  - [Proceedings of the National Gastroenterology Week, 17-22 November 2007, Leon,
      Mexico].

PMID- 18323034
TI  - The osteo-articular section of the RBRS, a fifteen-year-old story.

PMID- 18323035
TI  - New data question treatment for oxaliplatin neurotoxicity.

PMID- 18323036
TI  - [Preoperative preparation and examinations before scheduled cardiosurgical
      intervention].
AB  - In our article we inform about complete preoperative preparation and about
      required examinations before the scheduled cardiosurgical procedure. Important
      part of the preoperative preparation is also detailed instruction about the
      character of the operation, a way of its realization and about the operation
      risks. In the end of this article we discus the instruction of the patient about
      the types of the valvular prosthesis.

PMID- 18323037
TI  - [Clinical utility of bone markers in the evaluation and follow-up in patients
      with neoplastic bone diseases].
AB  - The biochemical markers of bone remodeling reflect the rates of bone resorption
      and bone formation in the whole body rather than in segments of the skeleton. The
      markers cannot be used for a diagnosis of bone disease. However, they are a
      valuable tool in the differential diagnosis, in the assessment of fracture risk
      independent of bone mineral density and, in the monitoring treatments of
      metabolic and neoplastic bone diseases as well as the side effects of some drugs
      on bone (e.g., adjuvant treatment with selective inhibitors of aromatase). This
      review provides characteristics of the markers currently used to assess
      neoplastic bone diseases and, their clinical values for stratification and
      monitoring treatments. Currently used markers provide sufficient specificity.
      However, their sensitivities under various clinical situations have to be
      respected. The clinical utility of the markers requires their standardization and
      availability.

PMID- 18323038
TI  - [Essential hypertension--syndrome, or compensatory mechanism].
AB  - Diagnosis of essential hypertension is created per exclusionem--with exclusion of
      all, so called secondary hypertensions (nephrogenic, endocrine conditioned etc).
      Idea and the name-essential hypertension are unclear. We have a lot of hypotheses
      about mechanisms of hypertension but no one is explaining satisfactorily the
      "fixation" of hypertension. From this point of view essential hypertension looks
      more like a syndrome than disease sui generis. Authors analyzed all possible
      pathways of hypertension origin as well as compensatory mechanisms in peripheral
      circulation in effort to reach relevant tissue perfusion. If these mechanisms
      lead to salt and water retention the best mode of the treatment would be to
      influence volume and blood vessels lumen. It is clear that optimization of blood
      pressure is advantageous for prevention of vascular catastrophes (myocardial and
      cerebral infarction). Nevertheless inadequate lowering of the peripheral tissue
      perfusion (kidney, CNS) can lead to degenerative changes in tissues and to
      disturbances in centrally regulated processes of blood pressure.

PMID- 18323039
TI  - [Involvement of microRNAs in cancer biology and possibilities of their
      application to diagnostic and predictive oncology].
AB  - MicroRNAs (miRNAs) are large class of non-coding RNAs that post-transcriptionally
      regulate gene expression. Their ability of translational repression applied for
      example on oncogenes or tumor-suppressor genes indicates involvement of miRNAs in
      multi-step carcinogenesis. Evidences of miRNAs linkage to biological processes
      like apoptosis, proliferation, differentiation and cell survival are rapidly
      accumulating. Approximately 50% of miRNAs are located at fragile sites of
      chromosomes or regions known to be amplified or deleted in human cancer. That is
      why, non-coding miRNAs seem to be another level of genetic information which
      regulation is altered or lost during neoplastic growth. Expression profiles of
      miRNAs are successfully used for molecular classification, more exact diagnosis
      and prognosis of human cancers and reached analogical analytical characteristics
      like studies based on DNA micro-arrays technology and profiling of coding
      transcripts. In this review we attempt to introduce basic knowledge of miRNAs
      biogenesis and biological functions and in particular summarise reports focused
      on miRNAs in oncology research area.

PMID- 18323040
TI  - [The influence of very-low-calorie diet on soluble adhesion molecules and their
      gene expression in adipose tissue of obese women].
AB  - BACKGROUND: Adhesion molecules (AM) are proteins expressed on the endothelial
      surface that play an important role in development of endothelial dysfunction.
      Higher concentrations of AM were found in patients with atherosclerosis, obesity
      or type 2 diabetes mellitus. The aim of our study was to measure serum
      concentrations and gene expression of ICAM-1 (intercellular adhesion molecule 1),
      VCAM-1 (vascular adhesion molecule 1) and E-selectin in subcutaneous adipose
      tissue samples obtained by needle biopsy from obese women and healthy controls
      and to evaluate the effect of 3-weeks very-low-calorie diet (VLCD) on these
      parameters. METHODS AND RESULTS: 20 obese women (BMI 46.2 +/- 9.7 kg/m2) and 13
      lean control women (BMI 23.8 +/- 2.3 kg/m2) were included into the study. Gene
      expression of AM in subcutaneous adipose tissue was measured using RT-PCR, serum
      AM levels were measured by multiplex immunoanalysis. At the baseline, serum E
      selectin concentrations were higher in obese women compared to controls (24.4 +/-
      2.3 vs. 15 +/- 1,5 ng/ml, p < 0,05). 3 weeks of VLCD significantly decreased BMI
      and serum E-selectin levels. Baseline mRNA expression of E-selectin, ICAM-1 and
      VCAM-1 in subcutaneous adipose tissue was lower in obese relative to lean women
      (p < 0.05). Weight reduction increased ICAM-1 and VCAM-1 gene expression (p <
      0.05). CONCLUSIONS: Our results suggest that the subcutaneous adipose tissue is
      not the major source of the studied soluble adhesion molecules in obese women and
      that the regulation of AM local gene expression in subcutaneous adipose tissue
      probably differs from its circulating levels.

PMID- 18323041
TI  - [Cyclosporin A versus cyclophosphamide in the treatment of nephrotic syndrome in
      children].
AB  - BACKGROUND: The majority of cases of nephrotic syndrome in children is
      corticosensitive, however in some individuals aggressive cytotoxic therapy is
      necessary. Cyclosporin A and cyclophosphamide are widely used; however their
      relative effectiveness in maintaining remission of childhood nephrotic syndrome
      remains controversial. METHODS AND RESULTS: Effectiveness of long-term cytotoxic
      therapy (mean follow-up 7.4 years) in 63 children (mean age 6.19 +/- 4.30 years)
      with nephrotic syndrome was retrospectively analyzed; 14 patients suffered from
      corticosensitive, 33 from corticodependent and 16 from corticoresistant nephrotic
      syndrome. Corticotherapy alone was used in 15 patients (23.8%), cyclophosphamide
      was added in 27 (42.9%) and cyclosporin A in 38 cases (60.3%), while 17 patients
      (27%) were on both immunosuppressive agents. 84% children relapsed within 24
      months after cessation of cyclosporin A. In 8 corticoresistant nephrotic syndrome
      patients (61.5%) from 13 children treated with cyclosporin A no remission
      occurred, in 5 children (38.5%) was remission obtained within 10 weeks, however
      in 4 of them relapsed disease during cyclosporin A therapy. 19 (70.4%) of 27
      patients on cyclophosphamide therapy were in remission, in 8 of them (42.1%) even
      2 years after cyclophosphamide therapy. CONCLUSIONS: Cyclophosphamide therapy of
      childhood nephrotic syndrome is more effective in maintaining long-term remission
      than cyclosporin A treatment.

PMID- 18323042
TI  - [Psychomotor speed and speed of searching in semantic memory].
AB  - BACKGROUND: The aim of the study was to assess relations among psychomotor speed,
      speed of searching from semantic memory and aging using simple bedside tests.
      METHODS AND RESULTS: We included 95 healthy volunteers with mean age 45.8 +/- 17
      years (min. 20, max. 80 years) to this study. We measured time in the short
      version of semantic fluency test (recite 12 animals) and in 2 tests of
      psychomotor tempo. We detected significant slowing in all tests (ANOVA, p <
      0.001) during aging. CONCLUSIONS: Slowing of psychomotor speed and searching in
      semantic memory were detected during physiological aging. Further research is
      necessary to clarify, if these fast and easy tests will be useful in screening
      for dementia in clinical practice.

PMID- 18323043
TI  - [Migration trends of Czech physicians].
AB  - BACKGROUND: Empirical study on the migration trends in the Czech Republic was a
      part of the larger research project run by the Research Institute for Labour and
      Social Affairs in Prague. The physicians were identified as a high risk
      professional group from the point of view of "brain drain" which was expected
      after accession of the Czech Republic to EU. To identify how many of the Czech
      physicians consider migration during their professional life, the probability of
      the implementation of the migration intention, the most frequent destination
      countries and push-pull migratory factors. METHODS AND RESULTS: Questionnaire
      survey was basically a pilot study in which 462 respondents participated. Sample
      was not representative. Very high migration potential of the Czech physicians was
      empirically verified; 45% of the respondents theoretically considered migration
      as a possible life's career. Probability that they will actually emigrate is
      substantially lower. Based on the used migratory behavior model it is estimated
      that in the forthcoming years about 6% of the Czech hospital physicians will
      leave their homeland to work abroad. The most popular destination countries are
      the Great Britain, the Ireland, and the Germany. Push-pull migratory factors are
      as follows to get better income, to improve language competencies, to experience
      more professional working conditions. CONCLUSIONS: Decline of the Czech
      physicians due to migration is continuously mitigated by the physicians coming
      from Slovakia. To consider the total number of the physicians, dramatic shortage
      is not expected in the nearest future. There are some indicators suggesting
      higher probability of real migration among high specialized middle aged Czech
      physicians in comparison to the young physicians.

PMID- 18323044
TI  - [The political correctness and the medical thinking].
AB  - The "Political correctness" is a rather new--about 25 years old--and poorly
      defined phenomenon. It is being used in an attempt to improve and to "euphemize"
      the present language and the terminology in various areas. The author tries to
      show the impact of Political correctness upon the medical diagnostic skills and
      its possible disadvantages.

PMID- 18323046
TI  - [Thomas Hunt Morgan (1866-1945)].

PMID- 18323047
TI  - Extra testing and support will boost confidence in maths skills.

PMID- 18323048
TI  - What is going on?
AB  - Nursing is under fire and morale has plummeted. The challenge for the
      profession's leaders is to insist on the best for patients, and for nurses.

PMID- 18323049
TI  - Taking control.
AB  - Self-management of long-term conditions such as diabetes depends on health
      professionals recognising cultural aspects in patient education.

PMID- 18323050
TI  - Savage practice.

PMID- 18323051
TI  - Semi-structured interviews: guidance for novice researchers.
AB  - Nurses are increasingly involved in research, particularly qualitative research.
      This article aims to prepare nurses for conducting semi-structured research
      interviews.

PMID- 18323052
TI  - Recommended procedure for bedmaking in hospital.
AB  - Bedmaking is a key nursing skill that is essential for the promotion of patient
      comfort, hygiene and wellbeing. Bedmaking requires technical and practical skills
      and consideration should be given to issues of safety, moving and handling and
      infection control practices. In this article the recommended procedures for
      making an unoccupied bed and an occupied bed are described in detail with
      reference to supportive literature where relevant.

PMID- 18323053
TI  - Stroke care: a nursing perspective.
AB  - Nurses play a significant role in the care of patients who have had a stroke,
      whether in the acute stages or longer-term. This article summarises the signs and
      symptoms of stroke and the main risk factors. It outlines the role of the nurse
      in providing the best care and advice for stroke patients, their families and
      carers.

PMID- 18323055
TI  - Rights of access to all.

PMID- 18323054
TI  - Caring for patients with pilonidal sinus disease.

PMID- 18323056
TI  - Root and branch review of education.

PMID- 18323057
TI  - Source memory for unrecognized items: predictions from multivariate signal
      detection theory.
AB  - We report three experiments investigating source memory for words that were
      called "new" on a recognition test. In each experiment, participants could
      accurately specify the source of words that they failed to recognize. Results
      also demonstrated that source memory for unrecognized items varied with the bias
      to respond "old" in recognition decisions: Participants displayed unrecognized
      source memory when they were told that 25% of the recognition test words were old
      (promoting conservative responding) but not when they were told that 75% of the
      test words were old (promoting liberal responding). Our results were successfully
      predicted by a multivariate signal detection approach to recognition/source
      memory.

PMID- 18323058
TI  - Working memory load differentially affects tip-of-the-tongue states and feeling
      of-knowing judgments.
AB  - Tip-of-the-tongue states (TOTs) are judgments of the likelihood of imminent
      retrieval for items currently not recalled, whereas feeling-of-knowing judgments
      (FOKs) are predictions of successful recognition for items not recalled. The
      assumption has been that similar metacognitive processes dictate these similar
      judgments. In Experiment 1, TOTs and FOKs were compared for general information
      questions. Participants remembered four digits (working memory load) during
      target retrieval for half of the questions, and there was no memory load for the
      other questions. Working memory did not affect recall but decreased the number of
      TOTs and increased FOKs. In Experiment 2, participants maintained six digits
      during retrieval. TOTs decreased in the working memory condition, but FOKs
      remained constant. Experiment 3 replicated the results of Experiment 2 while
      asking for FOKs for recall. In each of the first three experiments, positive
      metacognitive judgments also affected working memory performance, supporting the
      idea that working memory and metamemory use similar monitoring processes. In
      Experiment 4, visual working memory did not affect TOTs or FOKs. The data support
      a view that TOTs and FOKs are separable metacognitive entities.

PMID- 18323059
TI  - Examining the relationship between free recall and immediate serial recall: the
      serial nature of recall and the effect of test expectancy.
AB  - In two experiments, we examined the relationship between free recall and
      immediate serial recall (ISR), using a within-subjects (Experiment 1) and a
      between-subjects (Experiment 2) design. In both experiments, participants read
      aloud lists of eight words and were precued or postcued to respond using free
      recall or ISR. The serial position curves were U-shaped for free recall and
      showed extended primacy effects with little or no recency for ISR, and there was
      little or no difference between recall for the precued and the postcued
      conditions. Critically, analyses of the output order showed that although the
      participants started their recall from different list positions in the two tasks,
      the degree to which subsequent recall was serial in a forward order was
      strikingly similar. We argue that recalling in a serial forward order is a
      general characteristic of memory and that performance on ISR and free recall is
      underpinned by common memory mechanisms.

PMID- 18323060
TI  - Semantic contribution to verbal short-term memory: are pleasant words easier to
      remember than neutral words in serial recall and serial recognition?
AB  - In the four experiments reported here, we examined the role of word pleasantness
      on immediate serial recall and immediate serial recognition. In Experiment 1, we
      compared verbal serial recall of pleasant and neutral words, using a limited set
      of items. In Experiment 2, we replicated Experiment 1 with an open set of words
      (i.e., new items were used on every trial). In Experiments 3 and 4, we assessed
      immediate serial recognition of pleasant and neutral words, using item sets from
      Experiments 1 and 2. Pleasantness was found to have a facilitation effect on both
      immediate serial recall and immediate serial recognition. This study supplies
      some new supporting arguments in favor of a semantic contribution to verbal short
      term memory performance. The pleasantness effect observed in immediate serial
      recognition showed that, contrary to a number of earlier findings, performance on
      this task can also turn out to be dependent on semantic factors. The results are
      discussed in relation to nonlinguistic and psycholinguistic models of short-term
      memory.

PMID- 18323061
TI  - Proactive interference from items previously stored in visual working memory.
AB  - This study investigates the fate of information that was previously stored in
      visual working memory but that is no longer needed. Previous research has found
      inconsistent results, with some showing effective release of irrelevant
      information and others showing proactive interference. Using change detection
      tasks of colors or shapes, we show that participants tend to falsely classify a
      changed item as "no change" if it matches one of the memory items on the
      preceding trial. The interference is spatially specific: Memory for the preceding
      trial interferes more if it matches the feature value and the location of a test
      item than if it does not. Interference results from retaining information in
      visual working memory, since it is absent when items on the preceding trials are
      passively viewed, or are attended but not memorized. We conclude that people
      cannot fully eliminate unwanted visual information from current working memory
      tasks.

PMID- 18323062
TI  - Are awareness questionnaires valid? Investigating the use of posttest
      questionnaires for assessing awareness in implicit memory tests.
AB  - Two experiments--one employing a perceptual implicit memory test and the other a
      conceptual implicit memory test--investigated the validity of posttest
      questionnaires for determining the incidence of awareness in implicit memory
      tests. In both experiments, a condition in which none of the studied words could
      be used as test responses (i.e., the none-studied condition) was compared with a
      standard implicit test condition. Results showed that reports of awareness on the
      posttest questionnaire were much less frequent in the none-studied condition than
      in the standard condition. This was especially true after deep processing at
      study. In both experiments, 83% of the participants in the none-studied condition
      stated they were unaware even though there were strong demands for claiming
      awareness. Although there was a small bias in the questionnaire (i.e., 17% of the
      participants in the none-studied condition stated they were aware), overall,
      there was strong support for the validity of awareness questionnaires.

PMID- 18323063
TI  - The effects of repeated idea elaboration on unconscious plagiarism.
AB  - Unconscious plagiarism occurs in a recall task when someone presents someone
      else's idea as his or her own. Recent research has shown that the likelihood of
      such an error is inflated if the idea is improved during the retention interval,
      but not if it is imagined. Here, we explore the effects of repeating the
      elaboration phase during the retention interval. Participants in a group first
      generated alternate uses to common objects before elaborating the ideas either by
      imagining them or by improving them. This elaboration phase occurred once, twice,
      or not at all. Later, they attempted to recall their original ideas and generate
      new ideas. Repeated imagery did not inflate unconscious plagiarism on either
      task. In contrast, repeating the improvement phase increased plagiarism to
      dramatically high levels in the recall task. The latter effect might be
      particularly pertinent to real-world cases of plagiarism in which the ideas under
      dispute have been the subject of creative development over many occasions.

PMID- 18323064
TI  - False working memories? Semantic distortion in a mere 4 seconds.
AB  - False memories are well-established, episodic memory phenomena: Semantically
      related associates are confidently and erroneously remembered as studied items.
      We report four experiments yielding similar effects in a working memory paradigm.
      Four semantically related words were retained over a brief interval. Whether or
      not the interval was filled with a math verification task, semantically related
      lures were mistakenly recognized as members of the memory set and took longer to
      reject than did unrelated negative probes. In a short-term recall task, semantic
      intrusions exceeded other errors (e.g., phonemic). Our results demonstrate false
      memory effects for a subspan list when a mere 4 sec was given between study and
      test. Such rapid semantic errors presumably result from associative processing,
      may be related to familiarity-based proactive interference in working memory, and
      are consistent with recent models that integrate short- and long-term memory
      processes.

PMID- 18323065
TI  - Processing fluency affects subjective claims of recollection.
AB  - Previous studies that have used the remember-know paradigm to investigate
      subjective awareness in memory have shown that fluency manipulations have an
      impact on "know" responses but not on "remember" responses (e.g., Rajaram, 1993),
      a finding typically accounted for by invoking inferential processing in judgments
      of familiarity but not of recollection. However, in light of several researchers'
      criticisms of this procedure, as well as findings documenting the influence of
      processing fluency on various subjective judgments, the present study was
      conducted in order to investigate whether judgments of recollection might also be
      subject to inferential processes and not solely the product of conscious
      retrieval. When the standard remember-know procedure was used (Experiment 1),
      manipulations of perceptual fluency increased "know" responses but had no effect
      on "remember" responses, replicating previous findings. However, when an
      independent ratings method was employed (Higham & Vokey, 2004), manipulations of
      perceptual fluency (Experiment 2) and conceptual fluency (Experiment 3) reliably
      increased claims of both familiarity and recollection, suggesting that the
      conclusion that fluency affects only "know" responses may be an artifact of the
      standard remember-know procedure.

PMID- 18323066
TI  - Individual differences, rereading, and self-explanation: concurrent processing
      and cue validity as constraints on metacomprehension accuracy.
AB  - The typical finding of metacomprehension studies is that accuracy in monitoring
      one's own level of understanding is quite poor. In the present experiments,
      monitoring accuracy was constrained by individual differences in both reading
      comprehension ability and working memory capacity (WMC), but rereading
      particularly benefited low-ability and low-WMC readers, effectively eliminating
      the relationship between monitoring accuracy and these reader characteristics. In
      addition, introducing a self-explanation reading strategy improved the accuracy
      of all the readers above mere rereading. The observed interaction between
      individual differences and rereading is interpreted in terms of concurrent
      processing constraints involved in monitoring while text is processed, whereas
      the more general self-explanation effect is interpreted in terms of accessibility
      of valid, performance-predicting cues.

PMID- 18323067
TI  - Cue-framing effects in source remembering: a memory misattribution model.
AB  - During source remembering, selectively emphasizing one source in the retrieval
      query "Is this item from Source A?" can yield different accuracy than emphasizing
      the alternate source in "Is this item from Source B?" even if those are the only
      two possible origins. One account of this cue-framing effect holds that it
      reflects different active monitoring strategies encouraged by the two cue frames.
      An item memory misattribution (IMM) model instead assumes that this effect
      reflects the uncontrolled use of item recognition during confirmatory source
      judgments, and an IMM model simulation predicted a quantitative relationship
      between recognition levels and the cue-framing effect. Experiments 1 and 3
      confirmed these predictions by using study repetitions to manipulate recognition
      levels, and Experiments 2 and 3 also demonstrated the effect with new source
      tasks not previously considered. The data suggest that, in addition to
      qualitative monitoring strategies, subjects also use the availability of item
      memory in a heuristic fashion during confirmatory source attributions.

PMID- 18323068
TI  - Adult age differences in binding actors and actions in memory for events.
AB  - Three experiments provide evidence for an age-related deficit in the binding of
      actors with their actions. Young and older adults were tested on their memory for
      a series of events, each involving an actor performing a simple action. Older
      adults had greater difficulty than did young adults at discriminating old events
      from novel conjunctions of familiar actors and actions, even when the two groups
      were equated on memory for each of those features in isolation by using a longer
      retention interval for young adults. These results are consistent with an age
      related associative deficit linked to declines in hippocampal and prefrontal
      cortical functioning. They further provide evidence that age differences in
      source monitoring are not limited to speech acts but, rather, generalize to more
      complex actions. Finally, they provide evidence for age differences in
      susceptibility to conjunction memory errors, stemming from decreased reliance on
      recollection and increased reliance on familiarity with increased age. Example
      videos may be downloaded from www.psychonomic.org/archive.

PMID- 18323069
TI  - A test of the peak-end rule with extended autobiographical events.
AB  - Forty-nine students went on vacation for an average of 7 days and sent daily text
      messages about the happiness they had experienced over the previous 24 h. After
      their vacation, they were questioned on the overall happiness they had
      experienced and were asked to recall the daily record of their happiness. The
      duration of the vacation had no effect on the subsequent evaluations, and
      participants were not able to recall the detail of their day-to-day changes in
      happiness. A number of summary measures provided reasonable prediction of the
      recalled overall happiness of the vacation. The peak-end rule was not an
      outstandingly good predictor. Overall, the results indicate much reconstruction
      of the affective states.

PMID- 18323070
TI  - Is task interference in event-based prospective memory dependent on cue
      presentation?
AB  - Whether having an intention produces a performance cost to ongoing activities
      (task interference) is central to theoretical claims regarding the mechanisms
      underlying cue detection in event-based prospective memory. Recent evidence
      suggests that task interference primarily reflects an attention allocation policy
      stored in memory when intentions are encoded. The present study examined whether
      these policies can change with ongoing task experience. In Experiment 1, task
      interference was more greatly reduced when expected cues were not presented than
      when they were. Experiment 2 replicated this effect when the importance of the
      prospective memory task was emphasized. In Experiment 3, task interference
      decreased with time, and this decrease was greater when expected cues were not
      presented than when they were. Cue presentation is crucial to maintenance of
      attention allocation policies established by task instructions. This is the first
      article to demonstrate changes in task interference with ongoing task experience
      without forewarning individuals of the relevance of upcoming ongoing task trials
      to intentions.

PMID- 18323071
TI  - Number of cues influences the cost of remembering to remember.
AB  - A current focus in the prospective memory literature is the extent to which a
      prospective memory task (remembering to perform a future action) interferes with
      ongoing activities (defined in this study as lexical decision latencies). In the
      present study, participants had to detect one, two, three, four, five, or six
      prospective memory cues. Results showed no significant increase in lexical
      decision latencies with one or two targets; however, significant costs emerged
      with three or more targets. Furthermore, task interference showed a linear
      increase in task costs for word trial performance but not for nonword trial
      performance. Practical and theoretical implications of these findings are
      discussed.

PMID- 18323072
TI  - Facilitative interactions of model- and experience-based processes: implications
      for type and flexibility of representation.
AB  - People are often taught using a combination of instruction and practice. In prior
      research, we have distinguished between model-based knowledge (i.e., acquired
      from explicit instruction) and experience-based knowledge (i.e., acquired from
      practice), and have argued that the issue of how these types of knowledge (and
      associated learning processes) interact has been largely neglected. Two
      experiments explore this issue using a dynamic control task. Results demonstrate
      the utility of providing model-based knowledge before practice with the task, but
      more importantly, suggest how this information improves learning. Results also
      show that learning in this manner can lead to "costs" such as slowed retrieval,
      and that this knowledge may not always transfer to new task situations as well as
      experientially acquired knowledge. Our findings also question the assumption that
      participants always acquire a highly specific "lookup" table representation while
      learning this task. We provide an alternate view and discuss the implications for
      theories of learning.

PMID- 18323073
TI  - Discourse structure and relative clause processing.
AB  - Studies in several languages have shown that subject-relative clauses are easier
      to process than object-relative clauses. Mak, Vonk, and Schriefers (2006) have
      proposed the topichood hypothesis to account for the preference for subject
      relative clauses. This hypothesis claims that the entity in the relative clause
      that is most topicworthy will be chosen as the subject. By default, the
      antecedent of the relative clause will be chosen as the subject of the relative
      clause, because it is the topic of the relative clause. However, when the noun
      phrase (NP) in the relative clause is also topicworthy, the preference for the
      antecedent to be the subject will disappear. This was confirmed in two
      experiments. In Experiment 1, we tested relative clauses with a personal pronoun
      in the relative clause. We obtained a preference for object-relative clauses, in
      line with the assumption that personal pronouns refer to a discourse topic and
      are thus topicworthy. In Experiment 2, the discourse status of the NP in the
      relative clause was manipulated; either it was not present in the preceding
      context, or it was the discourse topic. The experiment showed that when the NP in
      the relative clause refers to the discourse topic, the difficulty of object
      relative clauses is reduced, in comparison with relative clauses with an NP that
      is new in the discourse, even in the absence of any explicit cue in the relative
      clause itself. The experiments show that discourse factors guide processing at
      the sentence level.

PMID- 18323074
TI  - Capturing and holding attention: the impact of emotional words in rapid serial
      visual presentation.
AB  - When two masked, to-be-attended targets are presented within approximately 500
      msec of each other, accurate report of the second target (T2) suffers more than
      when targets are presented farther apart in time--an attentional blink (AB). In
      the present study, the AB was found to be larger when taboo words were presented
      as a first target (T1), as compared with the AB found when emotionally neutral,
      negative, or positive words were presented as T1, suggesting that taboo words
      received preferential attentional processing. Comparable results were also
      obtained when taboo words were presented as to-be-ignored distractors in single
      target rapid serial visual presentation (RSVP). Arousal, but not valence, ratings
      of the emotional words predicted accuracy on subsequent targets in both dual- and
      single-task RSVP. Recognition memory for taboo words accounted fully for the
      negative relationships between arousal ratings and accuracy on subsequent
      targets, suggesting that arousal-triggered changes in attentional allocation
      influenced encoding of taboo words at the time they were encountered.

PMID- 18323075
TI  - Underspecification of syntactic ambiguities: evidence from self-paced reading.
AB  - Syntactically ambiguous sentences are sometimes read faster than disambiguated
      strings. Models of parsing have explained this tendency by appealing either to a
      race in the construction of alternative structures or to reanalysis. However, it
      is also possible that readers of ambiguous sentences save time by strategically
      underspecifying interpretations of ambiguous attachments. In a self-paced reading
      study, participants viewed sentences with relative clauses that could attach to
      one of two sites. Type of question was also manipulated between participants in
      order to test whether goals can influence reading/parsing strategies. The
      experiment revealed an ambiguity advantage in reading times, but only when
      participants expected superficial comprehension questions. When participants
      expected queries about relative clause interpretation, disambiguating regions
      were inspected with more care, and the ambiguity advantage was attenuated.
      However, even when participants expected relative clause queries, question
      answering times suggested underspecified representations of ambiguous relative
      clause attachments. The results support the construal and "good-enough" models of
      parsing.

PMID- 18323076
TI  - "At least one" problem with "some" formal reasoning paradigms.
AB  - In formal reasoning, the quantifier "some" means "at least one and possibly all."
      In contrast, reasoners often pragmatically interpret "some" to mean "some, but
      not all" on both immediate-inference and Euler circle tasks. It is still unclear
      whether pragmatic interpretations can explain the high rates of errors normally
      observed on syllogistic reasoning tasks. To address this issue, we presented
      participants (reasoners) in the present experiments either standard quantifiers
      or clarified quantifiers designed to precisely articulate the quantifiers'
      logical interpretations. In Experiment 1, reasoners made significantly more
      logical responses and significantly fewer pragmatic responses on an immediate
      inference task when presented with logically clarified as opposed to standard
      quantifiers. In Experiment 2, this finding was extended to a variant of the
      immediate-inference task in which reasoners were asked to deduce what followed
      from premises they were to assume to be false. In Experiment 3, we used a
      syllogistic reasoning task and observed that logically clarified premises reduced
      pragmatic and increased logical responses relative to standard ones, providing
      strong evidence that pragmatic responses can explain some aspects of the errors
      made in the syllogistic reasoning task. These findings suggest that standard
      quantifiers should be replaced with logically clarified quantifiers in teaching
      and in future research.

PMID- 18323077
TI  - Needed: a few new coal plants.

PMID- 18323078
TI  - Do perfluoropolymers biodegrade into PFOA?

PMID- 18323079
TI  - Ceramic filter makes water treatment easy.

PMID- 18323080
TI  - Ocean fertilization--time to regulate?

PMID- 18323081
TI  - Energy efficiency as an energy resource.

PMID- 18323082
TI  - Will leaders learn from EU mistakes?

PMID- 18323083
TI  - Shrinking personal monitoring devices.

PMID- 18323084
TI  - Application of nontraditional stable-isotope systems to the study of sources and
      fate of metals in the environment.

PMID- 18323085
TI  - Improved field methods to quantify methane oxidation in landfill cover materials
      using stable carbon isotopes.
AB  - Stable carbon isotopes provide a robust approach toward quantification of
      methanotrophic activity in landfill covers. The field method often applied to
      date has compared the delta13C of emitted to anaerobic zone CH4. Recent
      laboratory mass balance studies have indicated thatthis approach tends to
      underestimate CH4 oxidation. Therefore, we examined the CH4-delta13C at various
      soil depths in field settings and compared these values to emitted CH4. At 5-10
      cm depth, we observed the most enrichment in CH4-delta13C (-46.0 to -32.1 per
      thousand). Emitted CH4-delta13C was more negative, ranging from -56.5 to -43.0
      per thousand. The decrease in CH4-delta13C values from the shallow subsurface to
      the surface is the result of processes that result in selective emission of 12CH4
      and selective retention of 13CH4 within the soil. Seasonal percent oxidation was
      calculated at seven sites representing four cover materials. Probe samples
      averaged greater (21 +/- 2%, p < 0.001, n = 7) oxidation than emitted CH4 data.
      We argue that calculations of fraction oxidized based on soil derived CH4 should
      yield upper limit values. When considered with emitted CH4 values, this combined
      approach will more realistically bracket the actual oxidation value. Following
      this guideline, we found the percent oxidation to be 23 +/- 3% and 38 +/- 16% for
      four soil and three compost covers, respectively.

PMID- 18323086
TI  - Processes controlling the thermal regime of saltmarsh channel beds.
AB  - Spatially and temporally continuous temperature measurements were collected over
      32 h using a fiber-optic distributed temperature sensing (DTS) system deployed
      along 330 m of two intertidal saltmarsh channel beds in northern California.
      Measured temperature gradients imparted ecosystem-scale structure to the
      saltmarsh tidal channel thermal regime, which was punctuated by potential warm
      and cold refugia. Anomalous bed temperatures of 2-4 degrees C occurred throughout
      the 1.3 tidal cycles at some locations. Discrete locations of consistently warm
      temperatures characterized sustained seepage of recently infiltrated tidal
      waters. Low-variance temperature anomalies were typically collocated with hidden
      microtopographic tributaries that facilitated mixing of warm surface waters and
      cold groundwater. Bed temperature gradients (approximately 2 degrees C/100 m,
      average) decreased from high temperatures similar to bay water at the channel
      mouths to low inland temperatures comparable to groundwater. The trends were
      maintained by cold groundwater discharge throughout the channels, which affected
      bed temperatures in proportion to channel reach exposure time; the opposing
      effect, conductive bed-warming by tidal waters, was proportional to flood
      duration. DTS is a promising tool for identifying spatial and temporal
      temperature patterns of hydroecological importance amidst complex natural
      systems.

PMID- 18323087
TI  - Methyl tert-butyl ether (MTBE) in public and private wells in New Hampshire:
      occurrence, factors, and possible implications.
AB  - Methyl tert-butyl ether (MTBE) concentrations > or = 0.2 /microg/L were found in
      samples of untreated water in 18% of public-supply wells (n = 284) and 9.1% of
      private domestic wells (n = 264) sampled in 2005 and 2006 in New Hampshire. In
      counties that used reformulated gasoline (RFG), MTBE occurred at or above 0.2
      microg/L in 30% of public- and 17% of private-supply wells. Additionally, 52% of
      public-supply wells collocated with fuel storage and 71% of mobile home park
      wells had MTBE. MTBE occurrence in public-supply wells was predicted by factors
      such as proximity to sources of fuel, land use, and population density, as well
      as low pH and distance from mapped lineaments. RFG use, land-use variables, and
      pH were important predictors of private-well MTBE occurrence. Variables
      representing sources of MTBE, such as the distance to known fuel sources, were
      not significant predictors of MTBE occurrence in private-supply wells. It is
      hypothesized that private wells may become contaminated from the collective
      effects of sources in high population areas and from undocumented incidental
      releases from onsite or proximal gasoline use. From 2003 to 2005, MTBE occurrence
      decreased in 63 public-supply wells and increased in 60 private-supply wells, but
      neither trend was statistically significant.

PMID- 18323088
TI  - Regional trend and tissue distribution of brominated flame retardants and
      persistent organochlorines in raccoon dogs (Nyctereutes procyonoides) from Japan.
AB  - The present study investigated concentrations and patterns of brominated flame
      retardants, such as polybrominated diphenyl ethers (PBDEs) and
      hexabromocyclododecanes (HBCDs), and persistent organochlorines (OCs) in liver
      and adipose tissues of raccoon dogs (RD: Nyctereutes procyonoides) collected from
      two metropolises and a local prefecture in Japan during 2001-2006. Relatively
      high concentrations of PBDEs were found in RD livers, while HBCD levels were the
      lowest among the measured organohalogen compounds. Among PBDE congeners, BDE 209
      was predominant in RDs from all the regions, indicating that pollution derived
      from the technical decaBDE product is extensive across Japan. On the other hand,
      concentrations of tetra- to nona-BDE congeners in RDs from a metropolis were
      significantly higher than those from the other two regions, implying that there
      were regional differences in the past usage of the technical tetraBDE and octaBDE
      products. Such a regional difference was also observed for HBCD levels. Lipid
      normalized concentration ratios of liver to adipose tissue (L/A ratio) for tri to
      hepta-BDE congeners were lower than 1.0 in the investigated eight RDs, suggesting
      lipid-dependent accumulation. However, the LA ratios of BDE 209 exceeded 1.0 in
      all the specimens, suggesting hepatic retention of this compound. In addition,
      lipid-dependent accumulation of a-HBCD was observed, but the L/A ratios of gamma
      HBCD were greater than 1.0 in some specimens. These results indicate that
      Japanese RDs have been recently exposed to BDE 209 and gamma-HBCD and accumulated
      both these compounds preferentially in blood-rich organs, probably due to their
      binding to proteins and/or rapid biotransformation, as reported in experimental
      rodents.

PMID- 18323089
TI  - Tracing of industrial aerosol sources in an urban environment using Pb, Sr, and
      Nd isotopes.
AB  - A comprehensive Pb-Sr-Nd isotope tracer study of atmospheric trace metal
      pollution has been performed in the urban environment of Strasbourg-Kehl. Filter
      dust of the principal pollutant sources (waste incinerators, thermal power plant
      and steel plant) and soot of car and ship exhausts have been analyzed. In
      addition tree barks (as biomonitors) and PM10 have been analyzed to trace and
      determine the distribution of the pollution in the environment. The industrial
      sources have highly variable epsilonNd values (-9.7 and -12.5 for incinerators
      and -17.5 for steel plant). Much higher epsilonNd values have been found for soot
      of car exhausts (-6 and -6.9). These high values make the Nd isotope system a
      powerful tool for the discrimination of traffic emissions but especially for the
      identification of diesel derived particles in the urban environment. The
      206Pb/207Pb isotope ratios of gasoline are low (1.089) compared to diesel soot
      (1.159). The 26Pb/207Pb ratios of 1.151-1.152 for the steel plant and 1.152 for
      the solid waste incinerator are close to the Pb isotope ratio of diesel. The
      87Sr/ 8Sr isotope ratios of the principal industrial sources vary significantly:
      0.7095 for the domestic solid waste incinerator, 0.709 for the steel plant, and
      0.7087 for car exhaust soot. PM10 aerosols collected in the urban center of
      Strasbourg show the influence of the pollutant sources at 3-7 km distance from
      the center. Most of the aerosols Pb isotopic compositions suggest Pb admixtures
      from at least three sources: a natural background and in function of the wind
      direction the domestic waste incinerator (S-wind) or the steel plant and the
      chemical waste incinerator (NE-wind). The traffic contribution can only be
      estimated with help of Nd isotopes. Therefore the clear identification of
      different pollutant sources in the urban environment is only possible by
      combining the three different isotope systems and is based on the fact that
      significant differences exist between the Pb, Sr, and Nd isotope ratios of the
      natural atmospheric background and pollutants containing Pb, Sr, and Nd of
      industrial origin with similar variable 206Pb/207Pb, 87Sr/ 86Sr, and 143Nd/144Nd.

PMID- 18323090
TI  - Aggregation and disaggregation of humic supramolecular assemblies by NMR
      diffusion ordered spectroscopy (DOSY-NMR).
AB  - Diffusion ordered nuclear magnetic resonance spectroscopy (DOSY-NMR) was applied
      to a number of fulvic (FA) and humic (HA) acids of different origin. Spectral
      separation achieved by DOSY based on diffusion coefficients (D), and correlated
      to molecular sizes by calibration standards, showed that carbohydrates had the
      largest molecular size in FA, whereas alkyl or aromatic components were the most
      slowly diffusing moieties in HA. At increasing concentrations, these components
      had invariably lower D values in DOSY spectra for all humic samples,thereby
      indicating an aggregation into apparently larger associations, whose increased
      hydrodynamic radius was confirmed by viscosity measurements. When humic solutions
      were broughtfrom alkaline to acidic pH (3.6), components diffusivity detected by
      DOSY increased significantly, suggesting a decrease of aggregation and molecular
      size. A general comparison of HA and FA molecular sizes was achieved by
      multivariate statistical analysis. While a larger extent of aggregation and
      disaggregation was observed for HA than for FA, no aggregation was detected,
      under similar conditions, for a true macropolymeric standard. Such difference in
      diffusion between a polymeric molecule and humic samples, is in line with the
      supramolecular nature of humic matter. The possible formation of humic micelles
      was also investigated by both changes of diffusivity in DOSY spectra and shift of
      1H NMR signals. Except for HA of peat and soil origin, revealing a self
      assembling in micelle-like structures at the 4 mg mL(-1) concentration, no other
      humic sample showed evidence of critical micelle concentration (cmc) up to 20 mg
      mL(-1). These results indicated that DOSY-NMR spectroscopy is a useful technique
      to evaluate components of different molecular size in natural humic
      superstructures.

PMID- 18323091
TI  - Monitoring polycyclic aromatic hydrocarbon pollution in the marine environment
      after the Prestige oil spill by means of seabird blood analysis.
AB  - In this study we tested the use of seabird blood as a bioindicator of polycyclic
      aromatic hydrocarbon (PAH) pollution in the marine environment. Blood cells of
      breeding yellow-legged gulls (Larus michahellis) were able to track spatial and
      temporal changes consistent with the massive oil pollution pulse that resulted
      from the Prestige oil spill. Thus, in 2004, blood samples from yellow-legged
      gulls breeding in colonies that were in the trajectory of the spill doubled in
      theirtotal PAH concentrations when compared to samples from unoiled colonies.
      Furthermore, PAH levels in gulls from an oiled colony decreased by nearly a third
      in two consecutive breeding seasons (2004 and 2005). Experimental evidence was
      gathered by means of an oil-ingestion field experiment. The total concentration
      of PAHs in the blood of gulls given oil supplements was 30% higher compared to
      controls. This strongly suggested that measures of PAHs in the blood of gulls are
      sensitive to the ingestion of small quantities of oil. Our study provides
      evidence that seabirds were exposed to residual Prestige oil 17 months after the
      spill commenced and gives support to the nondestructive use of seabirds as
      biomonitors of oil pollution in marine environments.

PMID- 18323092
TI  - Unified membrane fouling index for low pressure membrane filtration of natural
      waters: principles and methodology.
AB  - Membrane filtration is considered an important technology that can contribute to
      the sustainability of water supplies. However, its continued development
      necessitates the establishment of proper techniques for the assessment of
      membrane fouling. Unified Membrane Fouling Index (UMFI) was developed in this
      study in order to quantify and assess the fouling of low-pressure membranes (LPM)
      observed at various scales of water treatment. The foundation of UMFI is a
      revised Hermia model applied to both constant pressure and constant flux
      filtration. The adoption of UMFI makes it possible to simplify and standardize
      the bench-scale testing of membrane fouling potential by directly using the
      commercial LPM of interest. This approach can overcome a major challenge to
      fouling assessment, i.e., the membrane-specificity of fouling potential, which
      has not been wholly addressed by existing fouling indices. The fundamentals of
      UMFI are presented in this paper, together with the methodology for bench-scale
      testing. The application of UMFI to the assessment of the fouling of a LPM by a
      natural surface water is also discussed. Good agreement between bench-scale UMFI
      and pilot-scale UMFI was found, suggesting the validity of this new scientific
      concept for environmental applications.

PMID- 18323093
TI  - Particulate-phase and gaseous elemental mercury emissions during biomass
      combustion: controlling factors and correlation with particulate matter
      emissions.
AB  - Mercury emissions from wildfires are significant natural sources of atmospheric
      mercury, but little is known about what controls speciation of emissions
      important to mercury deposition processes. The goal of this study was to quantify
      gaseous elemental mercury (GEM) and particulate-phase mercury (PHg) emissions
      from biomass combustion to identify key factors controlling the speciation.
      Emissions were characterized in an exhaust stack 17 m above fires using a gaseous
      mercury analyzer and quartz-fiber filters. Fuels included fresh and air-dried
      leaves, needles, and branches with different fuel moistures (9-95% of dry weight)
      and combustion properties (e.g., from < 10 to 90% of fire durations characterized
      by flaming phases). Fuel moisture was the overall driving factor defining
      emissions, with GEM being the dominant fraction (> or = 95%) in low moisture
      fuels and substantial PHg contributions--up to 50% of total mercury emissions--in
      fresh fuels. High PHg emissions were observed during smoldering combustion
      whereas flaming-dominated fires showed insignificant PHg emissions. PHg mass
      emissions were correlated with particulate matter (PM; r2 = 0.67), organic carbon
      (OC; r2 = 0.63) and sulfur (S; r2 = 0.46) mass emissions, but not with elemental
      carbon (EC) nor with the total mercury emissions. These data suggest that the
      formation of PHg involves similar processes as the formation of particulate OC,
      for example condensation of volatile species onto preexisting smoke particles
      during cooling and dilution. Based on the observed relationship between PM and OC
      mass concentrations and published emission inventories, we estimate global PHg
      emissions by wildfires of 4-5 Mg yr(-1).

PMID- 18323094
TI  - Fate of prions in soil: interactions of RecPrP with organic matter of soil
      aggregates as revealed by LTA-PAS.
AB  - The contribution of soil organic matter (OM) to the adsorption of a recombinant
      prion protein (RecPrP) was studied in microcosm systems (soil aggregates from two
      different soils) before and after OM removal by low temperature ashing (LTA). The
      LTA technique allows a controlled removal of OM layer by layer, like a peeling of
      an onion skin, with minimal disturbance of the mineral matrix. Soil aggregates
      were selected as a representative model of the "in situ" conditions. Adsorption
      from batch vs percolation experiments were compared, and the aggregates were
      characterized by photoacustic Fourier-transform IR spectroscopy (PAS-FTIR). High
      affinity (H-type) adsorption isotherms were found with complete removal of RecPrP
      from solution for protein/soil ratios up to 1:62.5. OM removal from aggregates
      decreased the adsorbed RecPrP in amounts corresponding to 330-1000 microg mg(-1)
      of soil organic carbon (OC) indicating that native OM has specific adsorption
      capacity comparable and/or superior to the mineral matrix. The coupled LTA-PAS
      FTIR approach demonstrated that, albeit OM composition was homogeneous throughout
      the aggregates, its presence in the most external surfaces of the aggregates
      affects the diffusion dynamics of RecPrP within the aggregates during
      percolation.

PMID- 18323095
TI  - OYE flavoprotein reductases initiate the condensation of TNT-derived
      intermediates to secondary diarylamines and nitrite.
AB  - Polynitroaromatic explosives such as 2,4,6-trinitrophenol (picric acid) and 2,4,6
      trinitrotoluene (TNT) are toxic and recalcitrant environmental pollutants. They
      persist in the environment due to the highly inactivated pi system of their
      aromatic rings, which are inaccessible to dioxygenases that normally initiate the
      bacterial aerobic catabolism of (nitro-) aromatic compounds. Aside from reductive
      transformation of nitro side groups to hydroxylamines, trinitroarenes are prone
      to aromatic ring reductions by some flavin reductases to yield Meisenheimer mono
      and dihydride complexes. Here we show that the simultaneous accumulation of
      Meisenheimer complexes and aromatic hydroxylamines derived from TNT gives rise to
      the condensation of both types of reactive intermediates to secondary
      diarylamines and nitrite as the end-products of this environmentally relevant
      reaction sequence. As a consequence, overall mass balances of aerobic
      biotransformations of TNT become possible for the first time. In our study, the
      process of TNT activation was enzymatically initiated by the xenobiotic reductase
      B (XenB)-like flavin reductase of Pseudomonas putida JLR11 and then completed
      chemically by autodimerization. The structures of the formed end products were
      unequivocally elucidated by NMR.

PMID- 18323096
TI  - Impact of black carbon in the extraction and mineralization of phenanthrene in
      soil.
AB  - During the past century, increased biomass burning and fossil fuel consumption
      have drastically increased the input of black carbon (BC) into the environment,
      and that has been shown to influence the behavior of organic contaminants in
      soil. A study was conducted to investigate the effects of BC on the relationship
      between aqueous hydroxypropyl-beta-cyclodextrin (HPCD) extraction and microbial
      mineralization (bioaccessibility) of 14C-phenanthrene (10 mg kg(-1)) in four
      soils amended with 0, 0.1, 0.5, 1, 2.5, and 5% (% dry wt soil) activated
      charcoal, a type of BC. Mineralisation was monitored over 20 d incubation, within
      respirometric assays, using an inoculum containing a phenanthrene-degrading
      pseudomonad and compared to HPCD extraction (24 h) using 50 mM aqueous solution;
      analyses were conducted after 1, 25, 50, and 100 d soil-phenanthrene contact
      time. Statistical analyses revealed that for each soil the addition of BC led to
      significant (P < 0.001) reductions in both HPCD extractability and microbial
      mineralization. Linear correlations for BC concentrations of 0% (r2 = 0.95; slope
      = 0.89) and 0.1% (r2 = 0.67; slope = 0.95) revealed a highly significant (P <
      0.01) relationship between HPCD extractability and total mineralization (20 d),
      indicating a direct prediction of phenanthrene bioaccessibility by HPCD. However,
      in soils amended with 0.5, 1, 2.5, and 5% BC exhibited r2 values ranging 0.51
      0.13 and slopes of 2.19-12.73. This study has shown that BC strongly sorbs
      phenanthrene causing reductions in extractability and, to a lesser extent,
      bioaccessibility to degrading microorganisms.

PMID- 18323097
TI  - Sequestration of nonylphenol in sediment from Bohai Bay, North China.
AB  - The ubiquity of nonylphenol (NP) in aquatic environments has been well
      documented, and the long-term fate of NP in sediments is a concern from the
      viewpoint of risk assessment due to its endocrine-disrupting effects. This paper
      reports on the assessment of long-term fate of NP in marine sediments by
      determining extractable and nonextractable fractions of NP in surface sediments
      and a sediment core from Bohai Bay, North China. The extractable fraction was
      operationally defined as the fraction of NP that was extracted with a solvent
      mixture of methanol/methylene chloride, and the nonextractable fraction was the
      portion of NP that can be released from the sediments by alkaline hydrolyzing
      after the initial solvent extraction. The total concentrations (extractable and
      nonextractable) of NP were 3.4-34.3 ng/g dw in the surface sediments and 2.2-17.7
      ng/g dw in the sediment core. Depending on the sedimentation time, the percentage
      of nonextractable NP relative to the total NP in the core ranged from 38 to 99%.
      Based on the relationship between the percentage of nonextractable NP in
      sediments and sedimentation time, the sequestration rate of NP in the sediment
      core from Bohai Bay was estimated to be 0.94% x a(-1). These results have
      important implications in understanding the geochemical fate of NP in sediments.

PMID- 18323098
TI  - Target tissue selectivity and burdens of diverse classes of brominated and
      chlorinated contaminants in polar bears (Ursus maritimus) from East Greenland.
AB  - The tissue-specific composition of sum classes of brominated and chlorinated
      contaminants and metabolic/degradation byproducts was determined in adult male
      and female polar bears from East Greenland. Significantly (p < 0.05) higher
      concentrations of sigma-PCBs, various other organochlorines such as sigma-CHL,
      p,p'-DDE, sigma-CBz, sigma-HCHs, octachlorostyrene (OCS), sigma-mirex, dieldrin,
      the flame retardants sigma-PBDEs, and total-(alpha)-hexabromocyclododecane
      (HBCD), sigma-methylsulfonyl (MeSO2)-PCBs and 3-MeSO2-p,p'-DDE, were found in the
      adipose and liver tissues relative to whole blood and brain. In contrast, sigma
      hydroxyl (OH)-PCB, 4-OH-heptachlorostyrene and sigma-OH-PBDE concentrations were
      significantly highest (p < 0.05) in whole blood, whereas the highest
      concentrations of sigma-OH-PBBs were found in the adipose tissue. Based on the
      total concentrations of all organohalogens in all three tissues and blood, the
      combined body burden was estimated to be 1.34 +/- 0.12 g, where > 91% of this
      amount was accounted for by the adipose tissue alone, followed by the liver,
      whole blood, and brain. These results show that factors such as protein
      association and lipid solubility appear to be differentially influencing the
      toxicokinetics, in terms of tissue composition/ localization and burden, of
      organohalogen classes with respect to chemical structure and properties such as
      the type of halogenation (e.g., chlorination or bromination), and the presence or
      absence of additional phenyl group substituents (e.g., MeO and OH groups). The
      tissue- and blood-specific accumulation (or retention) among organohalogen
      classes indicates that exposure and any potential contaminant-mediated effects in
      these polar bears are likely tissue or blood specific.

PMID- 18323099
TI  - The release of lead from the reduction of lead oxide (PbO2) by natural organic
      matter.
AB  - PbO2 has been identified as an important scale in some distribution systems that
      historically use lead service lines and free chlorine for maintaining a
      disinfectant residual. The stability of this highly insoluble scale with respect
      to its reductive dissolution may play an important role in lead release into
      drinking water. In this study, we investigated the release of lead from a
      commercially available PbO2 in the presence of natural organic matter (NOM) using
      a hydrophobic acid extracted from the Iowa River. Experiments were conducted
      using synthetic solutions with different NOM concentrations, solution pH, and NOM
      samples with different levels of prechlorination. It was found that release of
      lead from PbO2 occurred both in solutions with and without NOM, and the extent of
      lead release increased with increasing NOM concentration and decreasing pH value.
      Furthermore, the released lead was Pb(II) and not particulate PbO2 conclusively
      showing that reductive dissolution occurred. Prechlorination of NOM reduced the
      rate of lead release. Our results indicate that PbO2 can be reduced both by water
      and NOM. Characterization of final solid phases by scanning electron microscopy
      and X-ray photoelectron spectroscopy are also presented.

PMID- 18323100
TI  - Removal of endosulfan and methoxychlor from water on carbon slurry.
AB  - A carbon slurry, produced in generators of fuel-oil-based industrial generators
      was converted into an effective and efficient adsorbent for the removal of
      endosulfan and methoxychlor from aqueous solution. The adsorbent was chemically
      treated, activated, characterized, and used for the adsorption of endosulfan and
      methoxychlor pesticides. The maximum adsorption was found at 90 min, 6.5 pH,
      0.025 g/L dose, and 25 degrees C temperature. Langmuir and Freundlich adsorption
      models were applied to analyze adsorption data, and the former was found
      applicable to this adsorption system in terms of relatively high regression
      values. The thermodynamic aspect of the process was also investigated by
      evaluating certain important parameters (enthalpy, free energy, and entropy of
      system). Kinetics of adsorption was found to follow the pseudo second order rate
      equation. The diffusion of pesticides into carbon slurry pores was suggested to
      be the rate controlling step by applying Bangham's equation. Adsorption on a
      column was also investigated in a continuous flow system. Adsorption efficiencies
      of endosulfan and methoxychlor were 34.11 and 36.06 mg/g in batch processes and
      32.62 and 33.52 mg/g in column operations, respectively.

PMID- 18323101
TI  - Straining of nonspherical colloids in saturated porous media.
AB  - We explore the effects of colloid shape on straining kinetics by measuring the
      filtration of spherical and nonspherical colloids within saturated columns packed
      with quartz sand. Our observations demonstrate that the transport of peanut
      shaped colloids matches the transport of spherical colloids with diameters equal
      to the minor-axis length of the peanut-shaped colloids. The straining rates of
      the spherical colloids vary linearly with the ratio of colloid diameter (d(p)) to
      sand-grain diameter (d(g)) for 0.0083 < d(p)/d(g) < 0.06. This linear
      relationship also quantifies the straining rates of the peanut-shaped particles
      provided that the particle's minor axis length is used for d(p). Results of pore
      scale simulations reveal that a peanut-shaped particle adopts a preferred
      orientation as it approaches a pore-space constriction such that its major axis
      tends to align with the local flow direction. The extent of this reorientation
      increases with the particle's aspect ratio. Findings from this research suggest
      that straining is sensitive to changes in colloid shape and thatthe kinetics of
      this process can be approximated on the basis of measurable properties of the
      nonspherical colloids and porous media.

PMID- 18323102
TI  - Linking solid phase speciation of Pb sequestered to birnessite to oral Pb
      bioaccessibility: implications for soil remediation.
AB  - Lead (Pb) sorption onto oxide surfaces in soils may strongly influence the risk
      posed from incidental ingestion of lead-contaminated soils. In this study, Pb was
      sorbed to a model soil mineral, birnessite, and was placed in a simulated
      gastrointestinal tract (in vitro) to simulate the possible effects of ingestion
      of a soil contaminated with Pb. The changes in Pb speciation were determined
      using extended X-ray absorption fine structure and X-ray absorption near edge
      spectroscopy. Birnessite has a very high affinity for Pb with a sorption maximum
      of 0.59 mol Pb kg(-1) (approximately 12% Pb sorbed by mass) in which there was no
      detectable bioaccessible Pb (< 0.002%). Surface speciation of the birnessite Pb
      was determined to be a triple corner sharing complex in the birnessite
      interlayer. Lead sorbed to Mn oxide in contaminated media will have a very low
      (approximately equal to 0) Pb bioaccessibility and present little risk associated
      with incidental ingestion of soil. These results suggest that birnessite, and
      other Mn oxides would be powerful remediation tools for Pb-contaminated media
      because of their high affinity for Pb.

PMID- 18323103
TI  - Dissolution, sorption, and kinetics involved in systems containing explosives,
      water, and soil.
AB  - Knowledge of explosives sorption and transformation processes is required to
      ensure that the proper fate and transport of such contaminants is understood at
      military ranges and ammunition production sites. Bioremediation of 2,4,6
      trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and related
      nitroaromatic compounds has met with mixed success, which is potentially due to
      the uncertainty of how energetic compounds are bound to different soil types.
      This study investigated the dissolution and sorption properties of TNT and RDX
      explosives associated with six different soil types. Understanding the
      associations that explosives have with a different soil type assists with the
      development of conceptual models used for the sequestration process, risk
      analysis guidelines, and site assessment tools. In three-way systems of
      crystalline explosives, soil, and water, the maximum explosive solubility was not
      achieved due to the sorption of the explosive onto the soil particles and
      observed production of transformation byproducts. Significantly different
      sorption effects were also observed between sterile (gamma-irradiated) and
      nonsterile (nonirradiated) soils with the introduction of crystalline TNT and RDX
      into soil-water systems.

PMID- 18323104
TI  - CCN activity and hygroscopic growth of organic aerosols following reactive uptake
      of ammonia.
AB  - Recent field observations suggest that ammonium salts of organic acids may be
      very important in accounting for aerosols' properties in many environments. In
      this study we present laboratory experiments and calculations on the influence of
      ammonia reaction with organic aerosol components and its effect upon their (1)
      subsaturation hygroscopic growth (HG) and (2) supersaturation cloud condensation
      nuclei (CCN) activity. By using adipic acid (slightly soluble), citric acid
      (soluble), and di(ethylene glycol) monovinyl ether (DEGMVE, nonacidic compound)
      aerosols we show the feasibility and importance of atmospherically relevant acid
      base neutralization by ammonia for different organic species. It is suggested
      that the formation of ammonium salts due to reaction of ammonia with slightly
      soluble organic acids (such as adipic acid) can affect the CCN activity and
      hygroscopic growth of aerosols with a significant organic component. It is
      further confined that the reaction involves carboxylic groups, it requires
      presence of water in the aerosol, and that the effects are stronger for less
      soluble organic acids.

PMID- 18323105
TI  - Investigation of the biodegradation potential of a fluoroacrylate polymer product
      in aerobic soils.
AB  - Biodegradation of fluorinated polymers is of interest to assess them as a
      potential source of perfluorocarboxylates (PFCAs) in the environment. A
      fluoroacrylate polymer product test substance was studied in four aerobic soils
      over two years to assess whether the fluorotelomer alcohol (FTOH) side chains
      covalently bonded to the polymer backbone may be transformed to form PFCAs. The
      test substance itself was not directly measured; instead, nine analytes were
      determined to evaluate biodegradation. Terminal biotransformation products
      measured included perfluorooctanoate (PFO), perfluorononanoate (PFN),
      perfluorodecanoate (PFD), perfluoroundecanoate (PFU), and
      pentadecafluorodecanoate (7-3 acid). The molar concentration of 8-2 fluorotelomer
      alcohol (8-2 FTOH) in the test substance, fluoroacrylate polymer and residual
      unreacted raw materials and impurities ("residuals") were compared with the molar
      concentrations of the terminal biotransformation products for mass balance and
      kinetic assessments. Over the two year time frame of the experimental study, the
      fluoroacrylate polymer showed a slight extent of potential biodegradation under
      the experimental conditions of the study. A biodegradation half-life of 1200-1700
      years was calculated for the fluoroacrylate polymer based on the rate of
      formation of PFO in aerobic soils. When the degradation rates of the
      fluoroacrylate polymer and residuals were applied to estimated total historic
      fluoroacrylate polymer production, use and disposal, the biodegradation of
      fluoroacrylate polymer and residuals is calculated to contribute less than 5
      tonnes of PFO per year globally to PFCAs present in the environment.

PMID- 18323106
TI  - Modeling reaction and transport of multiple species in water distribution
      systems.
AB  - A general framework for modeling the reaction and transport of multiple,
      interacting chemical species in drinking water distribution systems is developed.
      It accommodates reactions between constituents in both the bulk flow (through
      pipes and storage tanks) and those attached to pipe walls. The framework has been
      implemented as an extension to the well-known EPANET programmer's toolkit (a
      library of functions that simulates hydraulic behavior and water quality
      transport in pipe networks). The implementation allows modelers to define the
      particular species of interest and their chemical equilibrium and reaction rate
      equations in a natural fashion using standard functional notation. It also
      employs several different numerical methods, including a stiff differential
      equation solver, to solve the reaction/equilibrium system throughout the pipe
      network using the standard EPANET transport algorithm. The flexibility and power
      of the framework is demonstrated with two examples that model water quality
      dynamics governed by different reaction/equilibrium systems.

PMID- 18323107
TI  - Estimation of outdoor NO(x), NO(2), and BTEX exposure in a cohort of pregnant
      women using land use regression modeling.
AB  - Land use regression (LUR) has been successfully used to assess the intraurban
      variability of air pollution. In the INMA (Environment and Childhood) Study,
      ambient nitrogen oxides (NO(x) and NO(2)) and aromatic hydrocarbons (BTEX) were
      measured at 57 sampling sites in Sabadell (northeast Spain). Multiple regression
      models were developed to predict residential outdoor concentrations in a cohortof
      pregnantwomen (n = 657), using geographic data as predictor variables. The models
      accounted for 68 and 69% of the variance in NO(x) and NO(2) levels, respectively,
      with four predictor variables (altitude, land coverage, and two road length
      indicators). These percentages of explained variability could be further improved
      by replacing the two road length indicators with an ordinal indicator (road
      type). To our knowledge, this is the first study using LUR to assess the
      intraurban variability of BTEX in Europe, with a model including altitude and
      source-proximity variables that explained 74% of the variance in BTEX levels.
      These models will be used to study the association between prenatal exposure to
      air pollution and adverse pregnancy outcomes and early childhhod effects in the
      cohort.

PMID- 18323108
TI  - Differences in phosphorus and nitrogen delivery to the Gulf of Mexico from the
      Mississippi River Basin.
AB  - Seasonal hypoxia in the northern Gulf of Mexico has been linked to increased
      nitrogen fluxes from the Mississippi and Atchafalaya River Basins, though recent
      evidence shows that phosphorus also influences productivity in the Gulf. We
      developed a spatially explicit and structurally detailed SPARROW water-quality
      model that reveals important differences in the sources and transport processes
      that control nitrogen (N) and phosphorus (P) delivery to the Gulf. Our model
      simulations indicate that agricultural sources in the watersheds contribute more
      than 70% of the delivered N and P. However, corn and soybean cultivation is the
      largest contributor of N (52%), followed by atmospheric deposition sources (16%);
      whereas P originates primarily from animal manure on pasture and rangelands
      (37%), followed by corn and soybeans (25%), other crops (18%), and urban sources
      (12%). The fraction of in-stream P and N load delivered to the Gulf increases
      with stream size, but reservoir trapping of P causes large local- and regional
      scale differences in delivery. Our results indicate the diversity of management
      approaches required to achieve efficient control of nutrient loads to the Gulf.
      These include recognition of important differences in the agricultural sources of
      N and P, the role of atmospheric N, attention to P sources downstream from
      reservoirs, and better control of both N and P in close proximity to large
      rivers.

PMID- 18323109
TI  - Response of atmospheric particulate matter to changes in precursor emissions: a
      comparison of three air quality models.
AB  - Three mathematical models of air quality (CMAQ, CMAQ-MADRID, and REMSAD) are
      applied to simulate the response of atmospheric fine particulate matter (PM2.5)
      concentrations to reductions in the emissions of gaseous precursors for a 10 day
      period of the July 1999 Southern Oxidants Study (SOS) in Nashville. The models
      are shown to predict similar directions of the changes in PM2.5 mass and
      component (sulfate, nitrate, ammonium, and organic compounds) concentrations in
      response to changes in emissions of sulfur dioxide (SO2), nitrogen oxides
      (NO(x)), and volatile organic compounds (VOC), except for the effect of SO2
      reduction on nitrate and the effect of VOC reduction on PM2.5 mass. Furthermore,
      in many cases where the directional changes are consistent, the magnitude of the
      changes are significantly different among models. Examples are the effects of SO2
      and NO(x) reductions on nitrate and PM2.5 mass and the effects of VOC reduction
      on organic compounds, sulfate and nitrate. The spatial resolution significantly
      influences the results in some cases. Operational model performance for a PM2.5
      component appears to provide some useful indication on the reliability of the
      relative response factors (RRFs) for a change in emissions of a direct precursor,
      as well as for a change in emissions of a compound that affects this component in
      an indirect manner, such as via oxidant formation. However, these results need to
      be confirmed for other conditions and caution is still needed when applying air
      quality models for the design of emission control strategies. It is advisable to
      use more than one air quality model (or more than one configuration of a single
      air quality model) to span the full range of plausible scientific representations
      of atmospheric processes when investigating future air quality scenarios.

PMID- 18323110
TI  - Tableau input coupled kinetic equilibrium transport (TICKET) model.
AB  - TICKET is a general-purpose, multispecies reactive transport model that is based
      on the tableau structure in MINEQL. The model can be used in solving problems
      from simple chemical equilibrium calculations for batch systems to complex one
      dimensional, reactive transport computations for surface water, groundwater, and
      water treatment systems. To streamline model input and model formulation,
      specifications of equilibrium speciation (including homogeneous precipitation,
      solid solutions, adsorption, and ion exchange) and linear and nonlinear kinetic
      reactions are defined directly in the tableau. In addition, the burden of
      accounting for appearing and disappearing solid phases is circumvented by
      approximating homogeneous precipitation as a solid solution (with an insoluble
      seed). The solution technique for the model is based on a one-step algorithm and
      can be applied to both steady-state and fully implicit, time-variable problems.
      This approach is particularly well-suited in handling chemical speciation
      transport problems with fast, nonlinear reaction kinetics and transient chemical
      intermediates. TICKET model simulations are presented for several test cases to
      verify the computational scheme. A model application, which examines the effects
      of sorption and overlying dissolved oxygen concentration on Fe(II) and As(III)
      oxidation in a sediment column, is also presented to demonstrate the utility of
      TICKET in examining complex chemical speciation-transport behavior.

PMID- 18323111
TI  - Solubility of C60 in solvent mixtures.
AB  - The potential large-scale production of fullerene C60 and its widespread use in
      consumer products may translate into occupational and public exposure and in long
      term environmental exposure. To assess the risk and fate of C60 in the
      environment, it is important to understand its solvate formation in common
      industrial solvents as the solvates may affect various properties of C60
      including reactivity and toxicity, particularly when solvates occur in C60
      clusters. In this study, the solubility measurements in mixed solvent system can
      provide useful information about solvate formation. The solubility of C60 was
      measured in pure toluene, tetrahydrofuran, ethanol, and acetonitrile to be 3000,
      11, 1.4, and 0.04 mg/L, respectively. Additionally, the solubility of C60 was
      measured in mixtures of toluene-acetonitrile, toluene-ethanol, toluene
      tetrahydrofuran, and acetonitrile-tetrahydrofuran. The solubility data were
      modeled with some accuracy using Wohl's equation. The estimated crystal energy
      term for C60 in tetrahydrofuran was different than that in the other solvents,
      indicating that the C60 solid phase in equilibrium with tetrahydrofuran solution
      may be a solvated crystal.

PMID- 18323112
TI  - Metal bioaccumulation in aquatic species: quantification of uptake and
      elimination rate constants using physicochemical properties of metals and
      physiological characteristics of species.
AB  - Mechanistic bioaccumulation models are powerful tools in environmental risk
      assessment as they provide insight in varying accumulation patterns across
      species, contaminants, and conditions, and they are applicable beyond tested
      cases. In these models key parameters, as absorption and elimination rate
      constants, are predicted based on chemical specific properties and physiological
      characteristics. However, due to the complex environmental behavior of metals,
      the development of mechanistic bioaccumulation models has lagged behind that for
      organic chemicals. Absorption and elimination rate constants of organic
      substances have long been linked to their octanol-water partition coefficient,
      yet no equivalent quantitative relationships exist for metals. In the present
      study, we successfully related metal absorption rate constants to a metal
      specific property, the covalent index, and a species-characteristic, the
      ventilation rate. This quantitative relationship holds for a wide range of
      organisms and metals, i.e., 17 aquatic species and 10 metals, suggesting that a
      generic modeling approach of metal uptake kinetics is feasible for aquatic
      organisms. In contrast, elimination rate constants show no metal - specific
      character. Average, weight-corrected elimination rate constants are relatively
      similar among metals and species, suggesting that a single weight-corrected
      elimination rate constant can be used in bioaccumulation studies on aquatic
      species.

PMID- 18323113
TI  - Measurements of nanoparticles of organic carbon and soot in flames and vehicle
      exhausts.
AB  - We measured the size distribution and UV extinction spectra of carbonaceous
      nanoparticles present in the size range of 1-100 nm in the exhausts of 2004 model
      gasoline and diesel powered vehicles and compared the results with those obtained
      in premixed flames. In addition to soot particles, nanoparticles of organic
      carbon (NOC) were measured in the emissions of these test vehicles in significant
      number and mass concentrations. The number and mass concentration of NOC was
      higher than soot in gasoline vehicle emissions. In diesel emissions, NOC had a
      higher number concentration than soot in terms of number concentration, but in
      terms of mass concentration, soot was higher than NOC. The size (1-3 nm) and
      extinction spectra in the UV-visible (strong in the UV and transparent in the
      visible) of macromolecules/nanoparticles collected in water samples from the
      vehicles are similar to those measured in laboratory hydrocarbon-air flames,
      suggesting that these nanoparticles are formed in hydrocarbon combustion
      reactions. We advance the hypothesis that NOC in vehicle emissions are produced
      by high-temperature combustion processes and not by low-temperature condensation
      processes.

PMID- 18323114
TI  - Anaerobic biodegradation of ethylene dibromide and 1,2-dichloroethane in the
      presence of fuel hydrocarbons.
AB  - Field evidence from underground storage tank sites where leaded gasoline leaked
      indicates the lead scavengers 1,2-dibromoethane (ethylene dibromide, or EDB) and
      1,2-dichloroethane (1,2-DCA) may be present in groundwater at levels that pose
      unacceptable risk. These compounds are seldom tested for at UST sites. Although
      dehalogenation of EDB and 1,2-DCA is well established, the effect of fuel
      hydrocarbons on their biodegradability under anaerobic conditions is poorly
      understood. Microcosms (2 L glass bottles) were prepared with soil and
      groundwater from a UST site in Clemson, South Carolina, using samples collected
      from the source (containing residual fuel) and less contaminated downgradient
      areas. Anaerobic biodegradation of EDB occurred in microcosms simulating natural
      attenuation, but was more extensive and predictable in treatments biostimulated
      with lactate. In the downgradient biostimulated microcosms, EDB decreased below
      its maximum contaminant level (MCL) (0.05 microg/L) at a first order rate of 9.4
      +/- 0.2 yr(-1). The pathway for EDB dehalogenation proceeded mainly by
      dihaloelimination to ethene in the source microcosms, while sequential
      hydrogenolysis to bromoethane and ethane was predominant in the downgradient
      treatments. Biodegradation of EDB in the source microcosms was confirmed by
      carbon specific isotope analysis, with a delta13C enrichment factor of -5.6 per
      thousand. The highest levels of EDB removal occurred in microcosms that produced
      the highest amounts of methane. Extensive biodegradation of benzene,
      ethylbenzene, toluene and ortho-xylene was also observed in the source and
      downgradient area microcosms. In contrast, biodegradation of 1,2-DCA proceeded at
      a considerably slower rate than EDB, with no response to lactate additions. The
      slower biodegradation rates for 1,2-DCA agree with field observations and
      indicate that even if EDB is removed to below its MCL, 1,2-DCA may persist.

PMID- 18323115
TI  - Analysis of fin clips as a nonlethal method for monitoring mercury in fish.
AB  - Monitoring of mercury in fish typically involves removal of individuals from the
      sampled population and subsequent analysis of fillets. This study assessed
      whether the analysis of fins, structures routinely clipped to mark released fish
      in population studies, could provide a nonlethal approach for estimating mercury
      concentrations in axial muscle (fillets). We analyzed fillets and selected fins
      from 401 northern pike (Esox lucius) and 79 walleye (Sander vitreus) from 21
      lakes in Minnesota and Wisconsin, 19 Arctic grayling (Thymallus arcticus) from
      Toolik Lake, Alaska, and 14 winter flounder (Pseudopleuronectes americanus) from
      Long Island Sound, New York. On average, 83% of mercury in fins was
      methylmercury, and concentrations in the proximal portion were about half-those
      in the distal portion in pelvic fins. Mean concentrations of mercury in fins,
      averaged by species and fin type, ranged from 2.7 to 8.9% of those in fillets.
      Coefficients of determination (r2) for linear regressions of mercury
      concentrations in fillets against those in fins of individual fish ranged from
      0.04 to 0.96 among species and water bodies (median r2 = 0.52). The concentration
      in fin clips was a better predictor of mercury in fillets for individual Arctic
      grayling (r2 = 0.65, n = 12 and r2 = 0.84, n = 8) and winter flounder (r2 = 0.94,
      n = 14) than for individual northern pike (median r2 = 0.56) or walleye (median
      r2 = 0.22) from a given lake. In northern pike in the 400-500 mm total-length
      interval, the mean concentrations of total mercury in caudal fins and fillets,
      averaged by lake (n = 12), were strongly correlated (r2 = 0.95). The analysis of
      composited samples of fin clips from fish within a restricted length interval
      could, therefore, be a useful screening tool for assessing the relative mercury
      contamination of fish among different water bodies.

PMID- 18323116
TI  - Measurements of size-segregated emission particles by a sampling system based on
      the cascade impactor.
AB  - A special sampling system for measurements of size-segregated particles directly
      at the source of emission was designed and constructed. The central part of this
      system is a low-pressure cascade impactor with 10 collection stages for the size
      ranges between 15 nm and 16 microm. Its capability and suitability was proven by
      sampling particles atthe stack (100 degrees C) of a coal-fired power station in
      Slovenia. These measurements showed very reasonable results in comparison with a
      commercial cascade impactor for PM10 and PM2.5 and with a plane device for total
      suspended particulate matter (TSP). The best agreement with the measurements made
      by a commercial impactor was found for concentrations of TSP above 10 mg m(-3),
      i.e., the average PM2.5/PM10 ratios obtained by a commercial impactor and by our
      impactor were 0.78 and 0.80, respectively. Analysis of selected elements in size
      segregated emission particles additionally confirmed the suitability of our
      system. The measurements showed that the mass size distributions were generally
      bimodal, with the most pronounced mass peak in the 1-2 microm size range. The
      first results of elemental mass size distributions showed some distinctive
      differences in comparison to the most common ambient anthropogenic sources (i.e.,
      traffic emissions). For example, trace elements, like Pb, Cd, As, and V,
      typically related to traffic emissions, are usually more abundant in particles
      less than 1 microm in size, whereas in our specific case they were found at about
      2 microm. Thus, these mass size distributions can be used as a signature of this
      source. Simultaneous measurements of size-segregated particles at the source and
      in the surrounding environment can therefore significantly increase the
      sensitivity of the contribution of a specific source to the actual ambient
      concentrations.

PMID- 18323117
TI  - Intercomparison of measurement techniques for black or elemental carbon under
      urban background conditions in wintertime: influence of biomass combustion.
AB  - A generally accepted method to measure black carbon (BC) or elemental carbon (EC)
      still does not exist. An earlier study in the Vienna area comparing practically
      all measurement methods in use in Europe gave comparable BC and EC concentrations
      under summer conditions (Hitzenberger et al., 2006a). Under summer conditions,
      Diesel traffic is the major source for EC or BC in Vienna. Under winter
      conditions, space heating (also with biomass as fuel) is another important source
      (Caseiro et al., 2007). The present study compares the response of thermal
      methods (a modified Cachier method, Cachier et al., 1989; a thermal-optical
      method, Schmid et al., 2001; and two thermal-optical (TOT) methods using Sunset
      instruments, Birch and Cary, 1996 and Schauer et al., 2003) and optical methods
      (a light transmission method, Hansen et al., 1984; the integrating sphere method,
      Hitzenberger et al., 1996; and the multiangle absorption photometer MAAP, Petzold
      and Schonlinner, 2004). Significant differences were found between the TOT
      methods on the one hand and all other methods on the other. The TOT methods
      yielded EC concentrations that were lower by 44 and 17% than the average of all
      measured concentrations (including the TOT data). The largest discrepancy was
      found when the contribution of brown carbon (measured with the integrating sphere
      method) was largest.

PMID- 18323118
TI  - Incoherent broadband cavity-enhanced absorption spectroscopy in the near
      ultraviolet: application to HONO and NO2.
AB  - The first application of incoherent broadband cavity-enhanced absorption
      spectroscopy (IBBCEAS) in the near-ultraviolet for the simultaneous detection of
      two key atmospheric trace species, HONO and NO2, is reported. For both compounds
      the absorption is measured between 360 and 380 nm with a compact cavity-enhanced
      spectrometer employing a high power light-emitting diode. Detection limits of
      approximately 4 ppbv for HONO and approximately 14 ppbv for NO2 are reported for
      a static gas cell setup using a 20 s acquisition time. Based on an acquisition
      time of 10 min and an optical cavity length of 4.5 m detection limits of
      approximately 0.13 ppbv and approximately 0.38 ppbv were found for HONO and NO2
      in a 4 m3 atmospheric simulation chamber, demonstrating the usefulness of this
      approach for in situ monitoring of these important species in laboratory studies
      or field campaigns.

PMID- 18323119
TI  - Two dimensional transport characteristics of surface stabilized zero-valent iron
      nanoparticles in porous media.
AB  - Zero-valent iron nanoparticles (INP) were synthesized and stabilized using poly
      acrylic acid (PAA) to yield stabilized INP (S-INP). A two-dimensional physical
      model was used to study the fate and transport of the INP and S-INP in porous
      media under saturated, steady-state flow conditions. Transport data for a
      nonreactive tracer, INP, and S-INP were collected under similar flow conditions.
      The results show that unstabilized INP cannot be transported into groundwater
      systems. On the other hand, the S-INP can be transported like a tracer without
      significant retardation. However, the S-INP plume migrated downward as it moved
      horizontally in the physical model, indicating that small density gradients have
      significant influence on two-dimensional transport. The variable-density
      groundwater flow model SEAWAT was used to model the observed density-driven
      transport patterns. This is the first time a two-dimensional transport data set
      is reported for demonstrating the multidimensional transport characteristics of
      nanoparticles. The data shows the importance of density effects, which cannot be
      fully discerned using one-dimensional, column experiments. Finally, we also
      demonstrate that the numerical model SEAWAT can be used to predict the density
      driven transport characteristics of S-INP in groundwater aquifers.

PMID- 18323120
TI  - Response of Nitrobacter spp. ribosomal gene and transcript abundance following
      nitrite starvation and exposure to mechanistically distinct inhibitors.
AB  - The Nitrobacter spp. rRNA gene (rDNA) and relative rRNA transcript abundance
      (rRNAt/rDNA ratio) were evaluated in response to sudden changes in the nitrite
      oxidation rate. The rDNA abundance poorly indicated sudden transitions in the
      rate, whereas the relative rRNAt abundance usually varied quickly and
      significantly. In response to changes in nitrite concentration, 8 h were required
      for the rRNAt/rDNA ratio to transition from a minimum value at nitrite starvation
      (approximately 0.07) to a maximum value with excess nitrite present
      (approximately 4), and 5 h were required for this metric to return to the minimum
      value after nitrite starvation re-ensued. Generally, the relative rRNAt abundance
      dropped significantly after 4.5 h of exposure to three different inhibitors. A
      sharp decline in the rRNAt/rDNA ratio occurred during exposure to 3,5-DCP (from 4
      down to 0.2) even as the fractional inhibition level remained low (< 0.10); the
      minimum ratio value was observed when nitrite oxidation was completely inhibited.
      The ratio decreased significantly during exposure to azide (from 4 to 0.5) and H+
      (from 2 to 0.2), but only when the fractional inhibition levels were high (>
      0.8). Interestingly, when the pH was suddenly changed to 4.5, inhibiting nitrite
      oxidation completely, the rRNAt/rDNA metric did not decline suggesting that rRNAt
      processing was inhibited. This effect was not observed during severe inhibition
      with 3,5-DCP and azide. Overall, the findings indicate the relative rRNAt
      abundance can be used to closely track in situ Nitrobacter spp. activity and in
      most instances will reveal inhibition events with the potential to impact
      treatment performance in reactors where Nitrobacter spp. are dominant.

PMID- 18323121
TI  - Removing organic compounds from aqueous medium via wet peroxidation by gold
      catalysts.
AB  - A new heterogeneous Fenton-like system, consisting of supported Au catalysts and
      hydrogen peroxide, was proved to be effective in removing low level organic
      compounds (ca. 100 ppm) such as phenol, ethanol, formaldehyde, and acetone in
      aqueous solution. Among all gold catalysts the Au/ hydroxyapatite (Au/HAp)
      exhibits the highest activity, and even better than the conventional iron ions
      exchanged zeolite (Fe/ ZSM-5) catalyst. In particular, unlike the limited
      operational pH range (pH: 2 approximately 5) for the other heterogeneous Fenton
      catalysts such as Fe/ZSM-5, Au/HAp shows higher stability even in strong acid
      solution (pH approximately 2), due to almost no leaching of active metal from
      supports into solution. It can be potentially applied in treating the industrial
      wastewaters with strong acidity and purifying drinking water. In addition, in the
      case of complete oxidation of phenol, a plausible route was suggested for deep
      understanding of this process.

PMID- 18323122
TI  - Kinetics of simultaneous photocatalytic degradation of phenolic compounds and
      reduction of metal ions with nano-TiO2.
AB  - The simultaneous photocatalytic degradation of phenol and 4-nitrophenol and
      reduction of metal ions like copper (Cu2+) and chromium (Cr6+) was studied with
      solution combustion synthesized nanoanatase TiO2 (CS TiO2) and commercial
      titania, Degussa P-25. The presence of metal ion reduces the rate of degradation
      of phenol and 4-nitrophenol. It was found that Cu2+ reduction to Cu+ is
      accelerated in the presence of phenol. In the case of Cr6+, CS TiO2 enhances the
      initial adsorption of Cr6+ and complete reduction is achieved within the first 10
      min of UV irradiation. The presence of phenol or 4-nitrophenol also enhances the
      initial adsorption of Cr6+ and its reduction. The metal ion reduction in the
      presence of CS TiO2 is compared with that of Degussa P-25. The rate of reduction
      of metal ions in presence of Degussa P-25 is twice as slow as that of CS TiO2 in
      presence of both phenol and 4-nitrophenol. The presence of Cu2+ and Cr6+ also
      induces the formation of the intermediates which were not observed for the phenol
      CS TiO2 system. The formation and consumption of the intermediates are modeled
      with a simple series reaction mechanism. A detailed dual-cycle, multistep
      reaction mechanism of TiO2 photocatalysis for the simultaneous degradation and
      reduction is proposed and the model is developed following the network reduction
      technique. The kinetic rate constants in the model are evaluated for the systems
      studied.

PMID- 18323123
TI  - Heavy metal immobilization through phosphate and thermal treatment of dredged
      sediments.
AB  - Disposal of dredged sediments is expensive and poses a major challenge for harbor
      dredging projects. Therefore beneficial reuse of these sediments as construction
      material is highly desirable assuming contaminants such as heavy metals are
      immobilized and organics are mineralized. In this research, the effect of the
      addition of 2.5% phosphate, followed by thermal treatment at 700 degrees C, was
      investigated for metal contaminants in dredged sediments. Specifically, Zn
      speciation was evaluated, using X-ray absorption spectroscopy (XAS), by applying
      principal component analysis (PCA), target transformation (TT), and linear
      combination fit (LCF) to identify the main phases and their combination from an
      array of reference compounds. In dredged sediments, Zn was present as smithsonite
      (67%) and adsorbed to hydrous manganese oxides (18%) and hydrous iron oxides
      (15%). Phosphate addition resulted in precipitation of hopeite (22%), while
      calcination induced formation of spinels, gahnite (44%), and franklinite (34%).
      Although calcination was previously used to agglomerate phosphate phases by
      sintering, we found that it formed sparingly soluble Zn phases. Results from the
      U.S. EPA toxicity characteristic leaching procedure (TCLP) confirmed both
      phosphate addition and calcination reduced leachability of heavy metals with the
      combined treatment achieving up to an 89% reduction.

PMID- 18323124
TI  - Sustainable colloidal-silver-impregnated ceramic filter for point-of-use water
      treatment.
AB  - Cylindrical colloidal-silver-impregnated ceramic filters for household (point-of
      use) water treatment were manufactured and tested for performance in the
      laboratory with respect to flow rate and bacteria transport. Filters were
      manufactured by combining clay-rich soil with water, grog (previously fired
      clay), and flour, pressing them into cylinders, and firing them at 900 degrees C
      for 8 h. The pore-size distribution of the resulting ceramic filters was
      quantified by mercury porosimetry. Colloidal silver was applied to filters in
      different quantities and ways (dipping and painting). Filters were also tested
      without any colloidal-silver application. Hydraulic conductivity of the filters
      was quantified using changing-head permeability tests. [3H]H2O water was used as
      a conservative tracer to quantify advection velocities and the coefficient of
      hydrodynamic dispersion. Escherichia coli (E. coli) was used to quantify
      bacterial transport through the filters. Hydraulic conductivity and pore-size
      distribution varied with filter composition; hydraulic conductivities were on the
      order of 10(-5) cm/s and more than 50% of the pores for each filter had diameters
      ranging from 0.02 to 15 microm. The filters removed between 97.8% and 100% of the
      applied bacteria; colloidal-silver treatments improved filter performance,
      presumably by deactivation of bacteria. The quantity of colloidal silver applied
      per filter was more important to bacteria removal than the method of application.
      Silver concentrations in effluent filter water were initially greater than 0.1
      mg/L, but dropped below this value after 200 min of continuous operation. These
      results indicate that colloidal-silver-impregnated ceramic filters, which can be
      made using primarily local materials and labor, show promise as an effective and
      sustainable point-of-use water treatment technology for the world's poorest
      communities.

PMID- 18323125
TI  - Comparing surface residue transfer efficiencies to hands using polar and nonpolar
      fluorescent tracers.
AB  - Transfer of chemicals from contaminated surfaces such as foliage, floors, and
      furniture is a potentially significant source of both occupational exposure and
      children's residential exposure. Increased understanding of relevant factors
      influencing transfers from contaminated surfaces to skin and resulting dermal
      loading will reduce uncertainty in exposure assessment. In a previously reported
      study, a fluorescence imaging system was developed, tested, and used to measure
      transfer of riboflavin residues from surfaces to hands. Parameters evaluated
      included surface type, surface loading, contact motion, pressure, duration, and
      skin condition. Results of the initial study indicated that contact duration and
      pressure were not significant for the range of values tested, but that there are
      potentially significant differences in transfer efficiencies of different
      compounds. In the study reported here, experimental methods were refined and
      additional transfer data were collected. A second fluorescent tracer, Uvitex OB,
      with very different physicochemical properties than riboflavin, was also
      evaluated to better characterize the range of transfers that may be expected for
      a variety of compounds. Fluorescent tracers were applied individually to surfaces
      and transfers to skin were measured after repeated hand contacts with the
      surface. Additional trials were conducted to compare transfer of tracers and co
      applied pesticide residues. Results of this study indicate that dermal loadings
      of both tracers increase through the seventh brief contact. Dermal loading of
      Uvitex tends to increase at a higher rate than dermal loadings of riboflavin.
      Measurement of co-applied tracer and pesticide suggest results for these two
      tracers may provide reasonable bounding estimates of pesticide transfer.

PMID- 18323126
TI  - Cadmium toxicity in a marine diatom as predicted by the cellular metal sensitive
      fraction.
AB  - Prediction of metal bioaccumulation and toxicity in aquatic organisms has been
      based on the free ion activity (e.g., FIAM) or more recently on the binding with
      the biological/toxicological sites of action (e.g., biotic ligand model).
      However, metals are bound to various intracellular ligands that may control metal
      toxicity. In this study, we examined the bioaccumulation, subcellular
      distribution, and toxicity of Cd in a marine diatom, Thalassiosira
      nordenskioeldii, under different irradiance levels. The diatoms accumulated more
      cellular Cd under higher irradiance at low [Cd2+] concentrations, but the
      accumulation slowed down when the [Cd2+] concentration further increased,
      implying that cellular binding saturation had been reached. Among the five
      operationally defined subcellular fractions (metal-rich granule, cellular debris,
      organelles, heat-denatured protein [HDP], and heat-stable protein [HSP]), Cd was
      most bound to HSP, whereas it was least bound to HDP. Cd was redistributed with
      increasing [Cd2+] concentration from the biologically detoxified pool to the
      presumed metal-sensitive fractions (MSF, a combination of organelles and HDP),
      which led to higher cellular Cd accumulation, toxicity, and sensitivity. Although
      diatom growth inhibition was significantly related to [Cd2+] concentration and Cd
      cellular bioaccumulation, the calculated inhibition concentrations based on MSF
      or organelles exhibited the least difference, strongly suggesting that MSF can
      provide the better predictor of Cd toxicity under different irradiance levels
      compared with [Cd2+] concentration or cellular accumulation. Our results
      demonstrated that models predicting metal toxicity need to address the
      subcellular fates of metals and how they respond to external and internal
      conditions.

PMID- 18323127
TI  - Cross-species comparison of conazole fungicide metabolites using rat and rainbow
      trout (Onchorhynchus mykiss) hepatic microsomes and purified human CYP 3A4.
AB  - Ecological risk assessment frequently relies on cross-species extrapolation to
      predict acute toxicity from chemical exposures. A major concern for environmental
      risk characterization is the degree of uncertainty in assessing xenobiotic
      biotransformation processes. Although inherently complex, metabolite
      identification is critical to risk assessment since the product(s) formed may
      pose a greater toxicological threat than the parent molecule. This issue is
      further complicated by differences observed in metabolic transformation pathways
      among species. Conazoles represent an important class of azole fungicides that
      are widely used in both pharmaceutical and agricultural applications. The
      antifungal property of conazoles occurs via complexation with the cytochrome P450
      monooxygenases (CYP) responsible for mediating fungal cell wall synthesis. This
      mode of action has cause for concern regarding the potential adverse impact of
      conazoles on the broad spectrum of CYP-based processes within mammalian and
      aquatic species. In this study, in vitro metabolic profiles were determined for
      thirteen conazole fungicides using rat and rainbow trout (Oncorhynchus mykiss)
      liver microsomes and purified human CYP 3A4. Results showed that 10 out of the 13
      conazoles tested demonstrated identical metabolite profiles among rat and trout
      microsomes, and these transformations were well conserved via both aromatic and
      aliphatic hydroxylation and carbonyl reduction processes. Furthermore, nearly all
      metabolites detected in the rat and trout microsomal assays were detected within
      the human CYP 3A4 assays. These results indicate a high degree of metabolic
      conservation among species with an equivalent isozyme activity of human CYP 3A4
      being present in both the rat and trout, and provides insight into xenobiotic
      biotransformations needed for accurate risk assessment.

PMID- 18323128
TI  - Occurrence, synthesis, and mammalian cell cytotoxicity and genotoxicity of
      haloacetamides: an emerging class of nitrogenous drinking water disinfection
      byproducts.
AB  - The haloacetamides, a class of emerging nitrogenous drinking water disinfection
      byproduct (DBPs), were analyzed for their chronic cytotoxicity and for the
      induction of genomic DNA damage in Chinese hamster ovary cells. The rank order
      for cytotoxicity of 13 haloacetamides was DIAcAm > IAcAm > BAcAm > TBAcAm >
      BIAcAm > DBCAcAm > CIAcAm > BDCAcAm > DBAcAm > BCAcAm > CAcAm > DCAcAm > TCAcAm.
      The rank order of their genotoxicity was TBAcAm > DIAcAm approximately equal to
      IAcAm > BAcAm > DBCAcAm > BIAcAm > BDCAcAm > CIAcAm > BCAcAm > DBAcAm > CAcAm >
      TCAcAm. DCAcAm was not genotoxic. Cytotoxicity and genotoxicity were primarily
      determined by the leaving tendency of the halogens and followed the order I > Br
      > > Cl. With the exception of brominated trihaloacetamides, most of the toxicity
      rank order was consistent with structure-activity relationship expectations. For
      di- and trihaloacetamides, the presence of at least one good leaving halogen
      group (I or Br but not Cl) appears to be critical for significant toxic activity.
      Log P was not a factor for monohaloacetamides but may play a role in the
      genotoxicity of trihaloacetamides and possible activation of dihaloacetamides by
      intracellular GSH and -SH compounds.

PMID- 18323129
TI  - Global gene expression profiling of androgen disruption in Qurt strain medaka.
AB  - Androgen disrupting chemicals (ADCs) are endocrine disrupting chemicals (EDCs)
      that mimic or antagonize the effect of physiological androgens. Microarray-based
      detection of altered gene expression can be used as a biomarker of EDC exposure.
      Therefore, the purpose of this study was to identify and compare gene expression
      profiles of the androgen 11-ketotestosterone (11-KT), the antiandrogen flutamide
      (FLU), and the antiandrogenic fungicide vinclozolin (VIN), on Qurt medaka
      (Oryzias latipes). Biologically effective concentrations for 11-KT (100
      microg/L), VIN (100 microg/L), and FLU (1000 microg/L) determined in range
      finding studies were used for exposures. The oligonucleotide microarray included
      9379 probes for EDC-affected genes, medaka cDNAs, sequences from the medaka
      genome project, and the UniGene database. We found that treatment with FLU, VIN,
      and 11-KT caused significant (false discovery rate = 0.01) differential
      expression of at least 87, 82, and 578 genes, respectively. Two sets of
      responsive genes are associated to vertebrate sex differentiation and growth, and
      50 genes were useful in discriminating between ADC classes. The discriminating
      capacity was confirmed by a remarkable similarity of the antiandrogenic
      expression profiles of VIN and FLU, which were distinct from the androgenic
      profile of 11-KT. Gene expression profiles characterized in this study allow for
      reliable screening of ADC activity.

PMID- 18323130
TI  - Comment on "Impact of sulfur oxides on mercury capture by activated carbon".

PMID- 18323131
TI  - Tried and true? Nurses use, engage in research to improve care, enhance
      workplaces.

PMID- 18323132
TI  - Steady study: nurses' participation make unique contribution to women's health.
      Interview by Susan Trossman.

PMID- 18323133
TI  - The multicultural health care work environment.

PMID- 18323134
TI  - It's been quite a journey for longtime flight nurse. Interview by Susan Trossman.

PMID- 18323135
TI  - Leading the way in research on women and heart disease.

PMID- 18323136
TI  - What happens when I flush medications down the drain?

PMID- 18323137
TI  - Surviving shift work.

PMID- 18323138
TI  - What is your power to influence healthcare policy?

PMID- 18323139
TI  - PNEGers in Portland.
AB  - Continuing education and academic and staff development educators participated in
      an annual American Nurses Association (ANA) Council on Continuing Education
      conference for many years. When ANA eliminated its councils, the conference was
      continued by the Professional Nurse Educators Group (PNEG). Each fall, PNEG hosts
      a conference targeting educators in academia, continuing education, and staff
      development roles. It is the only conference where common issues can be
      discussed. This column focuses on the value of participating in PNEG as a way to
      connect with other educators.

PMID- 18323140
TI  - Autism: part I. Deficits, prevalence, symptoms, and environmental factors.
AB  - Autism is a neurodevelopmental disorder that is gaining the attention of public
      health, educators, and health care providers. This column reviews the deficits,
      prevalence, symptoms, and environmental factors.

PMID- 18323141
TI  - Tough questions: recognize and resolve communication breakdown.
AB  - This column discusses six tools for recognizing and resolving communication
      breakdown.

PMID- 18323142
TI  - Competency in nursing: a concept analysis.
AB  - Competency is a topic of great interest to educators and administrators in
      practice disciplines, particularly health care disciplines such as nursing. This
      article focuses on the role of competency in nursing. Through a concept analysis
      process, various elements of competency were assessed. The defining attributes of
      competency are the application of skills in all domains for the practice role,
      instruction that focuses on specific outcomes or competencies, allowance for
      increasing levels of competency, accountability of the learner, practice-based
      learning, self-assessment, and individualized learning experiences. The learning
      environment for competency assurance involves the learner in assessment and
      accountability, provides practice-based learning opportunities, and
      individualizes learning experiences.

PMID- 18323143
TI  - Competency development in new registered nurse graduates: closing the gap between
      education and practice.
AB  - The gap between a new registered nurse graduate's education for practice and
      actual practice requirements of new registered nurses has long been an accepted
      fact in nursing. This article describes the development of an intervention from
      the academic side of the gap to improve the competency of nursing students before
      graduation. The intervention is noteworthy because it was developed
      collaboratively between academia and practice. The three-pronged intervention
      included development of learning modules based on the top 10 high-risk, high
      volume patient conditions; faculty and staff educator development in learning
      strategies to enhance competency development; and sharing of products with the 84
      schools of nursing in Texas.

PMID- 18323144
TI  - The evolution of simulation and its contribution to competency.
AB  - Nurse educators are challenged to implement teaching strategies that promote
      learners' clinical competency and critical-thinking skills. Additionally, these
      educators are asked to base their curriculum decisions, teaching practices, and
      evaluation methods on current research findings. Simulation offers a unique mode
      for experiential learning and evaluation, but the appropriate use of the spectrum
      of simulation typology requires strategic planning. Although simulation provides
      educators with new educational opportunities, the potential use of simulation in
      competency testing cannot be achieved until educators and researchers acquire the
      knowledge and skills needed to use this education strategy, develop realistic
      case scenarios, and design and validate standardized and reliable testing
      methods. Numerous pressures exist for clinical settings to document the
      competencies of their employees. Simulation could be used in the practice
      environment to promote and validate the clinical judgment and competency of
      nurses.

PMID- 18323145
TI  - Evaluating continuing competency: a challenge for nursing.
AB  - Twenty-five nurse leaders met at an invitational conference in Texas to discuss
      professional nurse competency evaluation. Conference attendees who were statewide
      nursing leaders in practice, education, and administration identified ways to
      evaluate competency. Responses were recorded and clustered into the following
      patterns: (1) components of competency evaluation, (2) barriers and challenges to
      evaluating competency, and (3) recommendations for evaluating competency.
      Conference attendees reported competency includes the abilities to think in
      action, have confidence and clarity in decision making, and retrieve information
      throughout the career trajectory. Nurses must demonstrate the ability to access
      evidence-based information and synthesize it within the context of practice
      situations. Self-reflection and self-assessment are necessary components to
      competency evaluation for the improvement of nursing practice.

PMID- 18323146
TI  - Public policy on competency: how will nursing address this complex issue?
AB  - The evolving contexts in which nursing care is provided and the complexity of
      clients being served are raising new questions about the nature of nursing
      practice, the ways in which nurses can best be prepared for such practice
      settings, and how current staff can continually update their knowledge, skills,
      and abilities to provide competent care. It is imperative that the profession be
      forward looking as it reassesses the implications of assuring the public of a
      competent nursing work force. The mandate to prepare nurses differently to
      practice competently in future health care systems also suggests a different
      system for competency assessment. This article provides an overview of
      international, national, and state perspectives and approaches in addressing the
      issue of assuring competency from a public policy perspective, including one
      state's experience to date.

PMID- 18323147
TI  - Safeguarding patients through continuing competency.
AB  - To ensure patient safety, it is crucial that nursing change the paradigm from
      demonstrating competency to continuing competency.

PMID- 18323148
TI  - [Methods of quantitative proteomics].
AB  - In modern science proteomic analysis is inseparable from other fields of systemic
      biology. Possessing huge resources quantitative proteomics operates colossal
      information on molecular mechanisms of life. Advances in proteomics help
      researchers to solve complex problems of cell signaling, posttranslational
      modification, structure and functional homology of proteins, molecular
      diagnostics etc. More than 40 various methods have been developed in proteomics
      for quantitative analysis of proteins. Although each method is unique and has
      certain advantages and disadvantages all these use various isotope labels (tags).
      In this review we will consider the most popular and effective methods employing
      both chemical modifications of proteins and also metabolic and enzymatic methods
      of isotope labeling.

PMID- 18323149
TI  - [Age-related changes of albumin and actin of human myocardium].
AB  - In the human myocardium tissue, proteomic technologies revealed the products of 2
      genes (alpha-actin and albumin), existing as fragments; their appearance and
      increased contents correlated with age. The age-related variants differ from the
      mature forms by the absence of N-terminal fragments of the amino acid sequences.
      In the chronic ischemic heart disease (CIHD), these age-dependent proteins were
      found in 50% of cases (in the age group 31-40 years), while in the control group
      such combination was detected only in 10% of the examined individuals. Subsequent
      studies in this field would probably reveal molecular mechanisms responsible for
      impairment and/or ageing of the cardiac muscle and also of the adaptation
      dysadaptations mechanisms in the CIHD.

PMID- 18323150
TI  - [Spreading and mechanisms of antimicrobial resistance of microorganisms,
      producing beta-lactamases. Phenotypical screening for MBL producers
      (carbapenemases B1) among strains of Pseudomonas genus, isolated in cases of
      nosocomial infections].
AB  - Intrahospital strains (215) of the bacterial genus Pseudomonas isolated from
      patients of 30 Medical centers of 15 Russian regions have been investigated for
      antibiotic resistance. The bacterial cultures resistant to imipenem and/or
      meropenem were considered as metallo-beta-lactamase (MBL) producers. Production
      of subclass B1 MBL (carbapenemases) was evaluated by means of the double-disk
      approximation test using MBL inhibitor, EDTA. There were 55 P. aeroginosa strains
      (25.6%) resistant to imipenem and meropenem simultaneously; 19 isolates (8.8%) of
      P. aeroginosa were characterized by synergism between carbapenem and EDTA. The
      subclass B1 MBL producers are widely distributed in the intrahospital strain
      obtained from Moscow, Yaroslavl, Ekaterinburg, Omsk, and Tomsk hospitals.

PMID- 18323151
TI  - [Entrapment of herbal extracts in biodegradable microcapsules].
AB  - The microcapsules with entrapped herbal water-soluble extracts Plantago major and
      Calendula officinalis L. (HE) were prepared by LbL-adsorption of carrageenan and
      modificated chitosan onto CaCO3 microparticles with their subsequent dissolving
      after the treatment of EDTA. Entrapment of HE was performed by adsorption and co
      precipitation techniques. The co-precipitation provided better entrapment of HE
      compared to adsorption. In vitro release kinetics in an artificial gastric juice
      (AGJ) was studied. The HE release was shown to accelerate gastric ulcer treatment
      in a rat model.

PMID- 18323152
TI  - [The effect of mildronate and related substances on levels of thyroid hormones
      and some intermediates of lipid and carbohidrate metabolism in the hyperthyroid
      and hypothyroid rats].
AB  - We have investigated effects of Mildronate, gamma-butyrobetaine (GBB) and their
      combination ("Neomildronate") on the plasma levels of thyroid gland hormones and
      some intermediates of basal metabolism (free fatty acids, triglycerides, glucose)
      in rats with different dysfunctions of thyroid gland, including idiopathic
      hyperfunction and hypofunction induced by propylthiouracil or L-carnitin
      administration. Histological investigation of the thyroid gland was also
      performed. Intraperitoneal injections of Mildronate (150 mg/kg) during 20 days to
      Wistar male rats with elevated level of thyroid hormones and basal metabolism
      normalized thyroxine level and parameters of lipid metabolism. Mildronate, GBB
      and their combination did not affect the natural resurgence of rats with
      experimental hypofunction induced by propylthiouracil or L-carnitin
      administration. The possible biochemical role of given treatment in regulation of
      thyroid gland function is discussed.

PMID- 18323153
TI  - [Magnesium homeostasis: mechanisms and inherited disorders].
AB  - Magnesium is one of the major cations of biological systems. It plays an
      essential role in many cell processes. The importance of magnesium underlines its
      maintenance under the steady conditions according to the metabolic state of the
      cell. In the present review mechanisms of magnesium homeostasis, that have been
      intensively investigated during last decades using both pathophysiological and
      molecular genetic approaches, are considered. Disorders of magnesium homeostasis
      resulted in development of magnesium-deficient conditions, which are commonly
      found in various diseases (diabetes mellitus, cardiovascular diseases, chronic
      fatigue, alcoholism, psychiatric and neurologic diseases, etc.), stress condition
      and therapy with some kind of drugs. Special attention is paid to familial
      hypomagnesemias caused by genetic defects of magnesium transport systems.
      Overview of clinical and biochemical characteristics of twelve familial disorders
      is given and mechanisms of inherited magnesium homeostasis disorders as well as
      nine identified and mapped genes responsible for their development are
      considered. These genes encode subunits of ionic channels, co-transporters,
      modulators of transport systems and receptors controlling either intestinal
      absorption or renal reabsorption of magnesium. Recent advances in mechanisms of
      magnesium homeostasis will lead to insights in diagnostics, preventive medicine
      and treatment of magnesium-deficient conditions.

PMID- 18323154
TI  - [Basic principles of molecular conformation analysis for medical biologists].
AB  - The main principles of the analysis and optimization of molecular conformation,
      which is the bases for molecular modeling methods in the field of bioinformatics,
      are briefly described. The basic approaches to molecular models energy
      minimization are considered. The given lecture is included into a theoretical
      cycle "Bioinformatics and computer aided drug design" for students of Medical and
      biologic faculty RGMU (biochemists, biophysics and medical cybernetics). It can
      be also recommended for other medical and biological students, as well as for PhD
      students.

PMID- 18323155
TI  - [Study on interaction of acetaldehyde with thioalcohols by infrared
      spectroscopy].
AB  - The reaction of acetaldehyde with thioalcohols, Mesna (monothiol) and Unithiol
      (vicinal dithiol) was investigated by infrared spectroscopy. Unithiol was more
      active in the reaction of acetaldehyde fixation than Mesna. This property may
      explain high efficiency of peroral administration of Unithiol for treatment of
      postalcoholic intoxication (hangover).

PMID- 18323156
TI  - [Intestinal pseudo-obstruction associated with polymyositis successfully treated
      with somatostatin analog].

PMID- 18323157
TI  - [Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode
      (MELAS) with elderly onset].

PMID- 18323158
TI  - [Mumps infection with acute renal failure and acute sensorineural hearing loss].

PMID- 18323159
TI  - [Three cases of adult Still disease].

PMID- 18323160
TI  - [Hypersomnia as a presentation of paraneoplastic limbic encephalitis in a patient
      with adult T cell leukemia/lymphoma].

PMID- 18323161
TI  - [An autopsy case of dilated cardiomyopathy associated with congenital nemaline
      myopathy].

PMID- 18323162
TI  - [Generalized seizure and eruption of distal limbs in a patient with lymphomatoid
      granulomatosis].

PMID- 18323163
TI  - [Streptococcus toxic shock syndrome with severe pleuro-pulmonary necrosis].

PMID- 18323164
TI  - [Preoperative prediction of remnant renal function in nephron-sparing surgery:
      the usefulness of 99mTc-mercapto-acetyl-triglycine scintigraphy].
AB  - A total of 10 patients with the diagnosis of renal cell carcinoma (RCC) underwent
      nephron-sparing surgery between January 1990 and December 2001. Serial pre- and
      postoperative 99mTc-mercapto-acetyl-triglycine (MAG3) scans were obtained. To
      examine preoperative predictability of remnant renal function, values of remnant
      renal plasma flow (ERPF) predicted prior to surgery were compared with values
      measured postoperatively. With preoperative MAG3 data, we designed the range of
      interest (ROI) except for the tumor area and recalculated remnant ERPF values.
      Remnant ERPF values predicted preoperatively correlated significantly with the
      postoperatively measured values 99mTc-(196.4 +/- 69.1 ml/min/1.73 vs 171.3 +/-
      72.9 ml/min/1.73 [mean +/- SD], p > 0.05, r = 0.806). MAG3 dynamic
      renoscintigraphy appeared useful for preoperative prediction of remnant renal
      function after nephron sparing surgery.

PMID- 18323165
TI  - Clinical efficacy and tolerability of gosha-jinki-gan, Japanese traditional
      herbal medicine, in females with overactive bladder.
AB  - The efficacy and tolerability of a single-agent treatment with 7.5 g/day Gosha
      jinki-gan in Japanese females with overactive bladder were analyzed objectively
      with linguistically validated questionnaires. A total of 44 Japanese females
      diagnosed as having overactive bladder were enrolled. Before and after the
      treatment, urinary frequency during the daytime and sleep was counted for two
      days, and the International Prostate Symptom Score index scores and quality of
      life index scores were examined. The efficacy assessment was done by comparing
      the quality of life index scores. The total scores of International Prostate
      Symptom Score, quality of life index scores and urinary frequency during the
      daytime and sleep were significantly decreased, respectively. Objective
      evaluation with the quality of life questionnaire yielded a result of excellent
      in 7%, improved in 46%, unchanged in 41% and worsened in 7%. Adverse reactions
      were observed in 9%. Gosha-jinki-gan could be a safe and effective potential
      therapeutic alternative in females with overactive bladder.

PMID- 18323166
TI  - Quantitative analysis of survivin mRNA expression in bladder transitional cell
      carcinomas.
AB  - We assessed the expression levels of survivin mRNA in bladder transitional cell
      carcinoma (TCC) to provide additional information regarding its malignant
      potential. The real-time PCR method was used to detect the survivin mRNA level
      for 21 bladder tumor specimens, and for urinary exfoliated cells from 12 newly
      diagnosed bladder tumor patients. All bladder tumor specimens and 7 of 12 voided
      urine specimens expressed survivin mRNA. In tumor specimens, high grade, high
      stage tumors had the tendency to express more survivin mRNA. Of 12 superficial
      bladder tumor patients who had transurethral resection of bladder tumor (TURB), 3
      showed high survivin mRNA expression and intravesical recurrence after the
      surgery. However, for the patients who had total cystectomy due to invasive
      tumor, no relations were observed between the survivin mRNA expression level and
      development of local recurrence and/or distant metastasis. Our results suggested
      that the quantitative analysis of the survivin mRNA may indicate local malignant
      potential, which contribute to the possibility of an intravesical recurrence.

PMID- 18323167
TI  - [Preoperative magnetic resonance imaging in the management of the nonpalpable
      testis].
AB  - We evaluated the efficacy of magnetic resonance imaging (MRI) as the preoperative
      study in the management of the nonpalpable testis. From 1997 to 2005, a total of
      41 MRI was performed for the patients with nonpalpable testis and 42 testes were
      evaluated. The MRI showed 19 testes from 18 patients in the inguinal region.
      Eighteen testes were found in the inguinal region and one was intraabdominal
      during groin exploration. Six testes were pointed out to be intra-abdominal by
      MRI. Five testes were identified in the abdomen and one was disclosed to be
      vanishing testis. Seventeen testes could not be detected by MRI and they
      underwent laparoscopic or groin exploration. Four abdominal testes were
      identified. Thirteen patients had a diagnosis of vanishing testis. The
      sensitivity and the specificity of our MRI studies in predicting the presence of
      nonpalpable testis were 85.7% and 92.9%, respectively. Enlarged lymph node could
      be misdiagnosed as abdominal testis. Inguinal undescended testes can be diagnosed
      accurately with MRI. MRI is informative regarding the testis location and useful
      for limiting the area of surgical exploration.

PMID- 18323168
TI  - [Case of extensive retroperitoneal abscess in a subcutaneous mass].
AB  - A 69-year-old woman consulted a doctor for subcutaneous mass and left
      hydronephrosis. Abdominal CT showed a left retroperitoneal abscess from the left
      perirenal lesion to the ileocccal region, subcutaneous abscess and left ureteral
      stone. Percutaneous drainage and double J stent indwelling was performed.
      Retrograde pyelography revealed extravasation from upper calyx to perirenal
      space. The abscess fluid culture proved to be methicillin-resistant
      Staphylococcus aureus.

PMID- 18323169
TI  - [Case of fungal endophthalmitis from pyelonephritis caused by ureterolithiasis].
AB  - A 63-year-old woman presented with visual disturbance. A fever had been noted for
      11 days. Right eye visual acuity was 20/50. Left eye visual acuity was 20/20.
      Inflammatory cclls wcrc present in the right aqueous and the vitreous humor. Tbc
      right retina was edematous. The left retina and left ocular humors were normal.
      Urinalysis showcd many white blood cells. Urine culture showed Candida albicans.
      KUB revealed many small ureteral calculi bilaterally. A diagnosis of fungal
      endophthalmitis due to pyeloncphritis caused by ureterolithiasis was rendered.
      The paticnt rcccivcd an intravenous course of fosfiuconazole and fluconazole.

PMID- 18323170
TI  - [Successful preoperative interferon-alpha therapy of advanced renal cell
      carcinoma with tumor thrombus extending into the inferior vena cava: a case
      report].
AB  - We report a case of renal cell carcinoma in which interferon-a therapy was
      effective in reducing the tumor thrombus extending into the inferior vena cava. A
      66-year-old man was referred to our hospital with a complaint of macroscopic
      hematuria, cough and general fatigue. We made a diagnosis of a left renal cell
      carcinoma with tumor thrombus by imaging examination. Because his performance
      status was 3, a radical operation was considered risky. Twenty-two months after
      the start of interferon-a therapy, the tumor thrombus was markedly reduced in
      size, and the clinical response was evaluated as partial response by the response
      criteria for urological cancer treatrment. Because of improvement of the
      performance status and downsizing of tumor thrombus, we performed radical
      nephrectomy. Pathological examinations revealed that viable renal cell carcinomas
      were found in the primary lesion and the tumor thrombus. In some cases,
      interferon-alpha therapy is useful and safe in the treatment of the tumor
      thrombus. Furthermore, radical nephrectomy and complete resection of the tumor
      thrombus prolongs postoperative survival.

PMID- 18323171
TI  - [Urothelial carcinoma of ureter with neuroendocrine differentiation: a case
      report].
AB  - A 73-year-old woman complained of gross hematuria. Urine cytology showed small
      cell carcinoma (SmCC) cells mixed with urothelial carcinoma (UC) cells.
      Cystoscopy revealed a bladder tumor around the right ureteral orifice. Abdominal
      CT demonstrated severe right hydronephrosis. Pelvic MRI showed a mass
      (approximately phi5 cm) in the urinary bladder wall that protruded into the
      lumen. TUR biopsy of the bladder tumor was SmCC. With laparoscopic
      nephrectomy/open ureterectomy, distal end (approximately 10 cm) of the right
      ureter was tumorous and obstructed. The tumor invaded into the urinary
      bladder/peritoneum and was unresectable. The tumor of lower-end of ureter tumor
      was SmCC, showing neuroendocrine differentiation such as pseudo-rosette, positive
      Grimelius stain, and chromogranin A/NCAM/synaptophysin immunostaining. Proximal
      to this tumor, non-invasive UC spread superficially over entire length of the
      ureter to the renal pelvis. Abrupt transition from invasive SmCC to non-invasive
      UC was observed in the middle of the ureter. Post-operative adjuvant chemotherapy
      was discouraged due to senile dementia of the patient. The patient died nine
      months after the operation because of systemic progression of cancer.

PMID- 18323172
TI  - [Anaphylactoid purpura after intravesical therapy using bacillus Calmette-Guerin
      for superficial bladder cancer].
AB  - We report a very rare side effect, anaphylactoid purpula, after intravesical
      administration of bacillus Calmette-Guerin (BCG). A 83-year-old man presented
      with purpura located on his bilateral lower legs. He had received transurethral
      resections four times for superficial bladder tumors. Intravesical therapy using
      BCG was performed. During the treatment course, asymptomatic purpura was suddenly
      seen in the lower legs after the third administration. Lymphocyte stimulation
      test was highly positive for BCG. He was diagnosed with anaphylactoid purpura
      caused by BCG. Conservative treatment was selected because there were no
      concomitant diseases in other organs. There have been no signs of recurrence of
      tumors or purpura during the one-year follow-up. However, physicians need to be
      cautious of anaphylactoid purpura which could lead to severe diseases, such as
      renal failure, gastrointestinal dysfunction and systematic arthritis.

PMID- 18323173
TI  - [Incidental inverted papilloma during the clinical follow-up of superficial
      transitional cell carcinoma in the urinary bladder].
AB  - A 76-year-old woman presented with gross hematuria. She had received
      transurethral resections (TURBT) twice for superficial bladder tumors near the
      right orifice. All pathologic findings demonstrated low grade superficial
      transitional cell carcinoma (TCC). Cystoscopy showed the tumor lesions during the
      follow-up. Bladder tumors were completely harvested and pathologic examination
      revealed inverted papilloma. However, recurrent tumors were detected at the same
      location after 4 months' follow up. Although she came to our hospital for the
      purpose of TURBT, she complained of severe neck pain and was suddenly dead.
      Autopsy findings showed that dissecting aortic aneurism was the cause of death
      and the bladder tumor was low grade superficial TCC. The case reported here had a
      very rare pathologic finding with a history of superficial tumors located in the
      same areas in the urinary bladder.

PMID- 18323174
TI  - Anterior urethral valve in the fossa navicularis presenting as a split urinary
      stream in a child.
AB  - An anterior urethral valve is uncommon compared to a posterior urethral valve as
      a cause of lower obstructive uropathy. Furthermore, an anterior urethral valve in
      the fossa navicularis is extremely rare. We describe the case in a 6-year-old boy
      who presented with a split urinary stream. Endoscopy revealed an anterior
      urethral valve in the fossa navicularis, and we successfully incised the valve
      with a hook knife. We should consider the possibility of an anterior urethral
      valve in any child with an abnormal urinary stream.

PMID- 18323175
TI  - [Prostate cancer in a relatively young adult: a case report].
AB  - We report a case of prostate cancer in a 45-year-old. The patient was found to
      have an elevated prostate specific antigen (PSA) level at a general health check
      and was referred to our division. Serum level of PSA was 6.9 ng/ml. Digital
      rectal examination and magnetic resonance imaging revealed a small nodule on the
      right lobe. Transperineal needle biopsy of the prostate revealed adenocarcinoma
      at the bilateral lobe (Gleason score 3+4). Computed tomography and a bone scan
      showed no evidence of metastasis. The patient was diagnosed as cT2b, NO, MO, and
      underwent a radical prostatectomy. Patients younger than 45 with prostate cancer
      are rare, although the incidence of prostate cancer is increasing. Here, 25 cases
      previously reported in Japan in addition to the present case, are reviewed.

PMID- 18323176
TI  - [Inverted papilloma of the prostatic urethra: a report of two cases].
AB  - Two men with inverted papilloma of the prostatic urethra are reported. Case 1 was
      a 67-year-old man with complaints of gross hematuria and urinary retention.
      Urethroscopy revealed a smooth-surface tumor with a stalk at the prostatic
      urethra. Case 2 was a 76-year-old man with complaints of gross hematuria and
      urinary retention. In these cases, the tumors were resected transurethrally and
      were consistent with inverted papilloma histopathologically.

PMID- 18323177
TI  - [Two cases of liposarcoma of spermatic cord].
AB  - Liposarcomas are most commonly found in the extremities, in the retroperitoneum
      and, less often, in the head and neck area. The spermatic cord is a rare site of
      origin, accounting for about 3-7% of all liposarcomas. We report two cases of
      liposarcoma of spermatic cord. Case 1. A 69-year-old male presented with
      complaints of a painless left inguinal mass. MRI showed a huge fatty mass in the
      left inguinal region. The mass was removed with left testis and spermatic cord.
      Histopathological examination revealed a well-differentiated and dedifferentiated
      liposarcoma. The surgical margin was positive, so re-resection was performed.
      Complete excision was achieved after re-resection. Case 2. A 63-year-old male
      with the difficulty urinating had a left scrotal mass. Left radical orchiectomy
      was performed. Histopathological examination revealed a well-differentiated
      liposarcoma. These are the 84th and 85th cases of liposarcoma of the spermatic
      cord reported in Japan.

PMID- 18323178
TI  - [A case of dedifferentiated liposarcoma of the spermatic cord].
AB  - We report a case of dedifferentiated liposarcoma of the spermatic cord. A 79-year
      old man was referred to our hospital with the chief complaint of a painless right
      scrotal swelling. A hard mass was palpable beside the soft mass which was
      suspected of lipoma or liposarcoma, and under this mass there was right testis.
      Therefore, we performed a right radical orciectomy. Histopathological diagnosis
      was dedifferentiated liposarcoma of the spermatic cord. Dedifferentiated
      liposarcoma of the spermatic cord was rare, and preoperative diagnosis was
      difficult.

PMID- 18323179
TI  - [Off-pump coronary artery bypass grafting using in-situ right internal thoracic
      artery extended with radial artery as I-composite graft].
AB  - OBJECTIVE: The purpose of this study is to assess the feasibility of utilizing
      the proximal right internal thoracic artery (RITA) extended with the radial
      artery (RA) as I-composite graft (RITA-RA graft) in off-pump coronary artery
      bypass grafting (OPCAB), which preserves the left internal thoracic artery to the
      left anterior descending artery as an isolated graft and the ascending aorta no
      touch technique. METHODS: Between January 2002 and August 2006, 37 patients (aged
      67.4+/-7.5 years, 86.5% male) underwent OPCAB using RITA-RA graft. All grafts
      were harvested in a skeletonized fashion. RITA transected at the middle portion
      was extended with entirely dissected RA. RITA-RA graft was anastomosed to 1 or 2
      lateral artery in a parallel sequential pattern. RESULTS: The total number of
      distal anastomoses of RITA-RA graft was 48. The early graft patency rate was
      97.9%. Five cases (13.5%) needed intra-aortic balloon pumping support during
      operation. Only 1 patient (2.7%) required ventilator support longer than 24
      hours. The percentage of patients requiring homologous blood transfusion was
      13.5%. There was no cerebrovascular accident or mediastinitis in the
      postoperative course. All patients were discharged from hospital. CONCLUSIONS:
      OPCAB using RITA-RA graft is feasible and safe. It provides satisfactory early
      clinical and angiographic outcomes.

PMID- 18323180
TI  - [Surgical experience of 6 multiple primary lung cancers].
AB  - Recently, we often meet multiple primary lung cancers with ground glass opacity
      (GGO). It is necessary for us to find suitable strategy to each case. We report a
      rare case with 6 lesions all of which were resected surgically. A 60-year old
      male visited our hospital for examination of abnormal shadows on the chest X-ray.
      Computed tomography (CT) scan showed 5 GGO lesions in the lung field (2 in the
      left lower lobe, 2 in the right upper lobe, 1 in the right middle lobe). He
      underwent left S6 segmentectomy as a 1st surgery, followed by wedge resection of
      the right upper lobe with right middle as a 2nd surgery. Pathologically, they
      were type A and B of the Noguchi classification. After 3-year follow-up, a new
      lesion developed in the right lower lobe and was resected by right lower
      lobectomy. It was invasive papillary adenocarcinoma. As a consequence, 6 lesions
      were all removed safely. The patient has been well without recurrence for 1 year
      after the last surgery.

PMID- 18323181
TI  - [Right atrium rupture due to blunt trauma].
AB  - We report 2 cases of surgical treatment of blunt cardiac trauma. The
      postoperative course was uneventful in either case. Pericardial drainage in
      patients with cardiac rupture should be performed with preparation for
      thoracotomy. Case 1: A 34-year-old male, hit in the chest by a collapsing 700-kg
      steel rod, was transported to our hospital via ambulance. The patient was
      diagnosed as having a cardiac rupture by echocardiography and underwent emergency
      thoracotomy. The right atrium near the inferior vena cava (IVC) was damaged,
      though bleeding from the wound had already ceased. No suture hemostusis was
      needed. Case 2: A 63-year-old female was hit by a car and transported to our
      hospital due to blunt trauma to the chest. Low blood pressure and chest computed
      tomography demonstrated cardiac tamponade, and subxiphoid pericardial drainage
      was performed. Blood pressure was recovered, but persistent hemorrhage
      necessitated emergency thoracotomy, which revealed a laceration at the right
      atrium near IVC. The injury was sutured to achieve complete hemostasis.

PMID- 18323182
TI  - [Protection of visceral organs with an aortic occlusion balloon catheter and by
      femoral perfusion in aortic arch replacement].
AB  - A 68-year-old man developed hemoptysis. Prominent left 1st arch was pointed out
      by chest X-p, and enhanced computed tomography (CT) revealed 60-mm distal arch
      aneurysm. Protrusion of the aneurysm strongly suggested aorto-pulmonary fistula.
      The operation was performed via median sternotomy. Cardiopulmonary bypass was
      established with the ascending aorta cannulation. During systemic cool down, an
      aortic occlusion balloon (Equalizer) was inserted in the right femoral artery and
      its position was monitored by transesophageal echography. Femoral perfusion
      cannula was inserted in the right femoral artery distal to the site of the
      Equalizer insertion. When the rectal temperature reached 28 degrees C, Equalizer
      was inflated and femoral perfusion was started. After the aortic arch was
      incised, balloon-tipped cannula were inserted into the aortic arch vessels. At
      this point, separate antegrade cerebral perfusion and lower body perfusion were
      established. The aortic arch was replaced with woven Dacron tube graft. It took
      60 minutes to accomplish distal anastomosis, and urination was 80 ml during this
      period. Postoperative course was uneventful without renal dysfunction. This
      method of visceral organ protection seemed to be useful for the patients with
      impaired renal or liver function and for the patients whose distal anastomosis is
      difficult.

PMID- 18323183
TI  - [Surgical treatment of an endobronchial inflammatory pseudotumor].
AB  - A 62-year old man with an abnormal chest radiograph was referred to our hospital
      for further evaluation. Chest computed tomography (CT) revealed a 3.0 cm tumor on
      the hilum of the right S3 segment. Bronchofiberscopic findings showed a polypoid
      tumor arising from right B3. Brushing cytology under bronchofiberscopy couldnot
      diagnose the tumor. The tentative preoperative diagnosis was primary lung cancer
      or a metastatic lung tumor. To confirm the histopathological diagnosis, a right
      upper lobectomy was performed. Intraoperative histopathological examination
      showed a pulmonary inflammatory pseudotumor.

PMID- 18323184
TI  - [Postoperative penicillin-resistant streptococcus pneumonia in lung cancer
      patient].
AB  - A 78-year-old man underwent a left lower sleeve lobectomy and lymph node
      dissection for lung cancer. His postoperative course had been uneventful until
      postoperative day (POD) 3, but severe dyspnea occurred suddenly and the chest X-p
      showed infiltration shadow on POD 3. Streptococcus pneumonia antigen in the urine
      was elevated, suggesting pneumonia caused by Streptococcus pneumonia. The patient
      was treated with double dose of imipenem/cilastatin sodium and supported with a
      mechanical ventilator in an intensive care unit. Although the patient recovered
      from penicillin resistant Streptococcus pneumonia, he was suffered from
      Klebsiella sepsis and expired on the POD 26.

PMID- 18323185
TI  - [Method of proximal anastomosis with a new assist device].
AB  - Various devices have been invented for proximal anastomosis performed during
      coronary bypass surgery. Enclose II allows a handling of the needle to be similar
      to a single cross clamp proximal anastomosis with almost no blood loss. However,
      when creating the anastomotic hole, it is difficult to determine whether an
      incision into the aortic wall will extend to the intima, and in some instances
      there is a risk that the hemostatic membrane may be injured. With Enclose II's
      hemostatic confirmation tube, the hemostatic membrane is opened and the tube is
      inserted into the aortic wall. The vent plug of the extension tube is opened,
      blood fills between the aortic wall and the instrument, and air is removed. An
      isotonic saline solution is injected and the pressure checked to insure that no
      air enters. An incision into the aortic wall is then made with a scalpel. When
      the intima is pierced, isotonic saline solution will gush out. In this way, one
      can prevent injury to the hemostatic membrane and ensure a correctly pierced
      anastomotic hole in the intima--even with just 1 punch.

PMID- 18323186
TI  - [Approach by clamshell incision for bilateral pulmonary metastasis].
AB  - In recent years thoracotomy by "clamshell incision" has frequently been chosen
      for heart-lung transplantation, bilateral lung tumors and mediastinal tumor
      merging into lung tumor because this approach provides very good visibility to
      access the whole bilateral lung including the lower lobe and mediastinal organs.
      In our hospital, 4 patients underwent bilateral thoracotomy by clamshell incision
      for pulmonary metastasectomy between 2001 and 2005. All cases had bilateral
      pulmonary metastases, and multiple wedge resection was performed. All lesions
      that were planned for resection on preoperative computed tomography (CT) could be
      resected. Regarding the surgical approach to bilateral pulmonary metastases that
      did not need lobectomy, clamshell incision is one of the useful approaches that
      can allow wedge resection anywhere in the whole lung. In cases that are expected
      multiple procedures, bilateral thoracotomy by clamshell incision is recommended
      because it allows another route for thoracotomy at reoperation.

PMID- 18323187
TI  - [Surgical cryoablation and left ventriculoplasty for electrical storm after acute
      myocardial infarction].
AB  - A 65-year-old man was referred to our hospital to treat recent anterior
      myocardial infarction. Coronary artery angiography showed acute occlusion of left
      anterior descending coronary artery (LAD) and chronic occlusion of right coronary
      artery. After emergent percutaneous coronary intervention for LAD, drug
      refractory electrical storm necessitating frequent electrical defibrillating
      cardioversion occurred. This patient successfully underwent surgical
      cryoablation, left ventriculoplasty and coronary revascularization. At 2 years
      and 10th month after the operation, he is well without limitation of daily
      activities and any evidence of myocardial ischemia and ventricular tachycardia.

PMID- 18323188
TI  - [Aortic arch replacement placing priority on cardiac and cerebral reperfusion].
AB  - In this report, aortic arch replacement was performed successfully in 2 cases
      with our modified method placing priority on the cardiac and cerebral
      reperfusion, resulting in no postoperative cardiac or neurological complication.
      One was a 63-year-old man with old cerebral infarction and ischemic heart
      disease, and the other was a 72-year-old man with severe stenosis of the left
      common carotid arteries. Our method is similar to so-called "arch first
      technique". First, the ascending aorta is clamped and proximal anastomosis is
      accomplished during core cooling, followed by reconstruction of the
      brachiocephalic arteries under deep hypothermic circulatory arrest. Then
      perfusion of the heart and brain is restarted, while distal anastomosis is
      performed. It was proved that the method had several possible advantages such as
      minimized duration of brain ischemia and deep hypothermia, and elimination of
      direct cannulation to the branches of the aortic arch and a separate perfusion
      circuit for the brain.

PMID- 18323189
TI  - [Off-pump coronary bypass grafting following percutaneous angioplasty and intra
      aortic balloon pumping insertion in a patient with severe peripheral vascular
      disease].
AB  - We describe our 1st case of off-pump coronary artery bypass grafting following
      percutaneous angioplasty (PTA) and intra-aortic balloon pumping (IABP) insertion.
      A 66-year-old man presented with cardiogenic shock due to acute coronary
      syndrome. He had concomitant peripheral vascular disease (PVD). He underwent
      coronary artery bypass grafting following PTA and IABP insertion. Even in an
      emergency case with PVD, PTA and IABP insertion could be an option to facilitate
      off-pump coronary artery bypass grafting.

PMID- 18323190
TI  - [Massive hemoptysis due to traction bronchiectasis caused by thoracic
      radiotherapy 23 years earlier].
AB  - We reported a 72-year-old woman who had a massive hemoptysis due to traction
      bronchiectasis in the left upper lobe. The patient underwent left radical
      mastectomy followed by thoracic radiotherapy for left breast cancer. The chest
      computed tomography showed traction bronchiectasis in the atrophic left upper
      lobe and the bronchial angiography showed hypervascularization of bronchial and
      internal thoracic arteries to the left upper lobe. Left upper lobectomy was
      performed after bronchial embolization for recurrent massive hemoptysis.
      Postoperative course was uneventful. Pathologic findings showed non-anatomical
      but clearly-bordered traction bronchiectasis with hypervascularized bronchial
      artery in the left upper lobe. These lesions were consistent with the field of
      the previous radiotherapy. Traction bronchiectasis causing massive hemoptysis
      should be considered as one of pulmonary sequelae after thoracic radiotherapy.

PMID- 18323191
TI  - [Informed consent in cardiovascular surgery].
AB  - Informed consent is a core component of partnership between the surgeon and the
      patient. Cardiovascular surgery is a high risk area in medical and surgical
      fields. An appropriate informed consent is essential for safety management of
      cardiovascular surgery and good relationship between the surgeon and the patient
      and his/her family. Concrete explanation of surgical procedures including the
      risk and benefit is important to share the common understanding of disease and
      treatment. Before the surgical procedure, we need to explain at least the
      following 5 contents, (1) name and extent of the disease, (2) contents of
      surgical procedure, (3) risk of surgery, (4) other options of treatment, and (5)
      prognosis of the disease.

PMID- 18323192
TI  - [Management of quadruple valves for severe infective endocarditis; report of a
      case].
AB  - A 74-year-old man had pustulant bilateral arthritis complicated with sepsis and
      disseminated intravascular coagulation (DIC). Microbiologic study of blood sample
      showed Streptococcus and methicillin resistant Staphylococcus aureus (MRSA). He
      was complicated with postulant diskitis since then. Medical treatment for DIC and
      administration of antibiotics were performed. Preoperative echocardiography
      revealed massive aortic regurgitation and vegetation of aortic valve, moderate
      pulmonary regurgitation and vegetation of pulmonary valve, massive mitral
      regurgitation, massive tricuspid regurgitation. He was diagnosed as infective
      quadruple valve endocarditis. He received aortic valve replacement, pulmonary
      valve replacement, mitral valve repair and tricuspid valve repair. Postoperative
      echocardiography showed satisfactory function of bioprosthesis. Postoperative
      course was uneventful.

PMID- 18323193
TI  - [Proximal anastomotic pseudoaneurysm due to gelatin-resorcin-formalin (GRF) glue
      after replacement of ascending aorta for acute aortic dissection; report of a
      case].
AB  - A 78-year-old man had previously undergone replacement of ascending aorta using
      gelatin-resorcin-formalin (GRF) glue for acute aortic dissection. Five years
      later, a follow-up computed tomography (CT) showed an aortic root pseudoaneurysm.
      Ultrasound cardiography revealed moderate aortic regurgitation and pseudoaneurysm
      of aortic root. Aortic root replacement was planned based on a clinical diagnosis
      of an anastomotic pseudoaneurysm of the aortic root. The patient was discharged
      without complication 26 days after surgery. In the histopathological examination,
      the necrotic change of smooth muscle cells in the aortic media was revealed.
      Previous reports suggests that the use of GRF glue for reconstructing the
      dissected aorta results in higher rates of postoperative redissection or
      pseudoaneurysm. Therefore, careful postoperative follow-up is necessary in such
      cases and further improvements in the quality of glue or alternative methods will
      be necessary to prevent problems in the first place.

PMID- 18323194
TI  - [Resected case of pulmonary arteriovenous malformation diagnosed with a brain
      abscess as a clinical manifestation; report of a case].
AB  - A 63-year-old female with Rendu-Osler-Weber disease had general fatigue and right
      hemiparesis. A computed tomography (CT) scan of her head demonstrated an
      enhancing cystic mass in the left frontal lobe, and it was diagnosed as a brain
      abscess and then drainaged. Thereafter, a pulmonary arteriovenous malformation
      (PAVM) identified in the left lingular segment by chest CT scan and the PAVM was
      resected by partial resection of the lung.

PMID- 18323195
TI  - [Paravertebral muscle metastasis from lung cancer; report of a case].
AB  - A 69-year-old man had undergone right S6 segmentectomy for lung cancer (poorly
      differentiated adenocarcinoma, pT2N0M0, stage IB). One years later, computed
      tomography (CT) showed abnormal shadow in the right paravertebral muscle of 7 x 5
      cm in size. The patient underwent resection of the tumor. The tumor was white,
      solid and elastic hard mass. Histopathologically, the tumor was paravertebral
      muscle metastasis from lung cancer. The patient was discharged on 23rd
      postoperative day, but died of other disease after 1 and a half month
      postoperatively.

PMID- 18323196
TI  - [Lung abscess which ruptured during the medical treatment of lung abscess; report
      of a case].
AB  - 63-year-old man was admitted to our hospital with fever and cough for about 2
      months. Laboratory data showed marked inflammatory changes, and chest computed
      tomography (CT) scans revealed right-sided hydrothorax, atelectasis of the right
      middle lobe, and a cystic mass in the right middle lobe. We diagnosed the
      patients as having lung abscess and empyema. Following the intravenous antibiotic
      chemotherapy, symptoms and laboratory data showed the improvement, however, on
      the 11th hospital day, he developed high fever again. A chest CT showed
      pneumopyothorax suggesting the rupture of lung abscess. Since the chest tube
      drainage was ineffective, open chest surgery was performed. Curettage of both
      thoracic and abscess cavity with closure of air leakage successfully cured the
      pyothorax.

PMID- 18323197
TI  - [Investigation and controlling measure of main diseases and pests on Artemisia
      annua].
AB  - According to the investigations in Guangxi area, there are 3 kind diseases and 11
      kind insect pests on Artemisia annua L. In which main diseases and peste are the
      stem rot, cataplexy, Myzus persicase, Agrotis ypsilon and Diarthronomyia
      chrysanthemi. This article reports the main symptom, the cause of disease, the
      shape characteristic, the harm situation emphatically as well as the preventing
      and controlling measure.

PMID- 18323198
TI  - [Study on effects of seed stock, cultivating density on the yields and volatile
      oil of Curcuma wenyujin].
AB  - OBJECTIVE: According to the study on effects of cultivating density and seed
      stock on the yield and volatile oil, to provide a scientific basis for
      standardized cultivating measures. METHODS: The yield and the content of volatile
      oil at harvest were counted and analyzed the variance by SPSS. RESULTS: The
      effect of cultivating density on the yields from 3 different medicinal parts of
      medical material was significant. The effect of seed stock on the yield of
      Rhizoma wenyujin concisa and Rhizoma wenyujin curcumae was significant, but to
      the yield of Radix wenyujin curcumae was very little. The mutual effect between
      cultivating density and seed stock was also very little. CONCLUSION: The
      cultivating density play an important role in the yields of Curcuma wenyujin.

PMID- 18323199
TI  - [Studies on HPLC-ELSD fingerprint of the Coleus forskohlii introduced in
      Tongcheng].
AB  - OBJECTIVE: To establish HPLC-ELSD fingerprint of Coleus forskohlii. METHODS:
      Chromatographic fingerprint of Coleus forskohlii was investigated by HPLC-ELSD
      and gradient elution mode was applied to chromatographic separation. RESULTS: The
      HPLC-ELSD fingerprint of Coleus forskohlii was established preliminarily.
      CONCLUSION: HPLC-ELSD fingerprint method is repeated and can be used in quality
      control of Coleus forskohlii. The active constituent in Coleus forskohlii is
      probably at equal pace between introduced in Tongcheng and provenance.

PMID- 18323200
TI  - [Study on HPLC fingerprint of processed Radix Angelicae Dahuricae].
AB  - OBJECTIVE: To establish HPLC fingerprint analysis for the quality control of
      processed Radix Angelicae Dahuricae. METHODS: HPLC fingerprint analysis of
      processed Radix Angelicae Dahuricae was developed Agilent C18 column (250 mm x
      4.6 mm, 5 microm) was used, with mixture of acetonitrile and 5% phosphorous acid
      mobile phase in a gradient mode. The flow rate was 1.0 mL/min. The wavelength of
      measurement was 254 nm. Fifteen batches of processed Radix Angelicae Dahuricae
      were determined. RESULTS: The methodological evaluation showed that the method
      had a good repeatability. CONCLUSION: The method can be used to identify and
      evaluate the quality of Radix Angelicae Dahuricae conveniently.

PMID- 18323201
TI  - [Microscopical identification of Scolopa chinensis].
AB  - OBJECTIVE: To study the microscopical features of Scolopa chinensis. METHODS: By
      microscope, the tissue characteristics and the powder characteristics were
      studied. RESULTS: The results are accurate and practical. CONCLUSION: These
      Characteristics can provide evidences for the identifcation of Scolopa chinensis.

PMID- 18323202
TI  - [Alkaloid constituents from silkworm dropping of Bombyx mori].
AB  - OBJECTIVE: To extract and isolate chemical constituents from the total alkaloids
      of silkworm dropping (Can Sha) of Bombyx mori L. METHODS: Chemical constituents
      were isolated by column chromatography with macroporous adsorbent resin, ion
      exchange resin and sephadex LH 20. The structures of the isolated compounds were
      determined by spectral means. RESULTS: Three compounds were isolated and
      identified as 1-deoxynojirimycin (1) , fagomine (2) , and 3-epifagomine (3) on
      the basis of their 1H-NMR, 13C-NMR spectra and ESIMS data. CONCLUSION: Compounds
      1-3 are isolated and identified from Can Sha for the first time.

PMID- 18323203
TI  - [Alkaloid constituents of Corydalis adunca].
AB  - OBJECTIVE: To study the alkaloid component of Corydalis adunca Maxim. METHODS:
      The constituents were isolated by chromatographic methods, their structures were
      elucidated by spectroscopic evidences. RESULTS: Three compounds were purified and
      their structures were identified, they were identified as dorydaline (I),
      dehydrocorydaline (II), dihydrosanguinarine (III). CONCLUSION: Compounds I , II
      are isolated from this plant for the first time.

PMID- 18323204
TI  - [Studies on chemical constituents from rhizomes of Panax notoginseng].
AB  - OBJECTIVE: To study the chemical constituents from rhizomes of Panax notoginseng.
      METHODS: The constituents were isolated and purified by various
      chromatogragraphic methods, all compounds were identified on the basis of special
      analysis and physicochemical characters. RESULTS: Eight compounds were isolated
      from the 80% alcohol extract of the rhizomes and their structures were identified
      as ginsenoside Rh4 (I), ginsenoside Rh1 (II), ginsenoside Re (III),
      notoginsenoside R1 (IV) , ginsenoside Rd (V), ginsenoside Rh1 (VI),
      notoginsenoside S (VII), notoginsenoside T (VIII). CONCLUSION: Compound I was
      isolated from this plant for the first time, Compound VII, VIII are isolated from
      rhizomes of Panax notoginseng for the first time.

PMID- 18323205
TI  - [Studies on chemical constituents of Valeriana officinalis].
AB  - From Valeriana officinalis L., 4 compounds were isolated and identified by
      various spectral analysis and chemical conversion, as valerenic acid, beta
      sitosterol, ursolic acid, 4, 4', 8, 8'-tetrahydroxy-3, 3'-dimethoxyl-dibenzyl
      ditetrahydrofuran and caryophyllene acide,valerane, naphthalene, linoleic acid,
      ethyl ester, myrtenyl acetate were identified by GC-MS. Ursolic acid and 4, 4',
      8, 8'-tetrahydroxy-3, 3'-dimethoxyl-dibenzyl-ditetrahydrofuran were discovered in
      this plant for the first time.

PMID- 18323206
TI  - [Studies on chemical constituents of Taxillus sutchuenenisis].
AB  - OBJECTIVE: To study the chemical constituents of Taxillus sutchuenenisis
      (Lecomte) Danser. METHODS: Chromatography and spectrum analysis were employed to
      isolated and elucidate the chemical constituents in the plant. RESULTS: 9
      compounds were isolated and identified as quercetin (I), quervetin 3-O-beta-D
      galactoside (II), isoquercitrin (III), quercitrin (IV), rutin (V), gallic acid
      (VI), ferulic acid (VII), beta-sitosterol (VIII), daucosterol (IX), respectively.
      CONCLUSION: Compounds III-IX are isolated from this plant for the first time. The
      work provide evidence for the exploitation and utilization of this plant resouce.

PMID- 18323207
TI  - [Determination of oridonin and rosemarinic acid in Rabdosia rubescens by HPLC].
AB  - OBJECTIVE: To establish the method for determining the content of oridonin and
      rosemarinic acid in Rabdosia rubescens by HPLC. METHODS: Using ODS-C18 column
      (150 mm x 4.6 mm, 5 microm), methanol-0.3% phosphoric acid (40:60), oridonin
      detection wavelength at 238 nm and rosemarinic acid at 329 nm. RESULTS: The
      average recovery oridonin was 97. 1% and rosemarinic acid was 99.3%. Oridonin
      relative standard deviation (RSD) was 2.8% and rosemarinic acid was 2.9%.
      CONCLUSION: This method can be used to determine the content of oridonin and
      rosemarinic acid in Rabdosia rubescens.

PMID- 18323208
TI  - [Studies on the methods of extract and determination of total tannins and gallic
      acids of the root of Euphorbia hylonoma].
AB  - OBJECTIVE: To determine total tannins and gallic acid of the root of Euphorbia
      hyloomla. METHODS: With the gallic acid as reference, tannins and gallic acid of
      the root of Euphorbia hylonoma were determined by ultraviolet spectrophtometer
      and high performance liquid chromatography, respectively. RESULTS: The content of
      tannins of the root of Euphorbia hylonoma were determined by different extract
      methods, including extracted by water, 70% alcohol, acetone on supersound, the
      determination data were 4.375%, 7.240%, 3.958%, respectively. When used
      recirculation method by water, 70% alcohol, acetone, the determination data were
      the determination data are 3.773%, 2.503%, 1.59%, respectively. The content of
      gallic acid of the root was 0.047%. CONCLUSION: Content of total tannins by
      alcohol super sound is the highest comparing with other extract methods, this
      method can used in extract of total Tannins of the root of Euphorbia hylonoma.

PMID- 18323209
TI  - [Effects of Rhaponticum uniflorum on activity and mRNA expression of CYP3A1 in
      rats hepatocytes].
AB  - OBJECTIVE: To study effects of Rhaponticum uniflorum on the activities and mRNA
      expression of cytochrome P4503A1 in rats hepatocytes. METHODS: Rat hepatocytes
      sandwich cultures were treated by Rhaponticum uniflorum in different
      concentrations (15.6, 31.2, 62.4 mg/ml) for 48 hours. The enzymic activities of
      CYP3A1 were reflected by the activities of liver microsomal erythromyeine N
      demethylase (ERD). The level change in the mRNA expression were tested by RT-PCR.
      RESULTS: After treatment with the medicine, there was concentration-dependent
      inhibition in both enzymic activity and mRNA level of CYP3A1 compared with the
      control. The rates of the inhibitory effect to CYP3A1 activity were 26.4%, 44.2%
      and 65.4% respectively, while those of the inhibitory effect to mRNA level were
      29.4%, 49.8% and 56.0%. CONCLUSION: Rhaponticum uniflorum inhibits the enzymic
      activity of CYP3A1 and lowers CYP3A1 expression at the transcriptive levels.

PMID- 18323210
TI  - [The protection of elemene on injured HUVECs induced by hydrogen peroxide].
AB  - OBJECTIVE: To evaluate the effect of elemene on the survival of normal human
      umbilical endothelial cells (HUVECs) and the protection of elemene on injured
      HUVECs induced by hydrogen peroxide (H2O2). METHODS: Normal HUVECs were treated
      with elemene 1-100 microg/ml for 24-72 hours, the survival rate of HUVECs was
      determined by tetrazolium assay (MTT). To evaluate the protective effect of
      elemene on HUVECs from H2O2 injury, HUVECs were injured by 1 mmol/L H2O2 and then
      different final concentrations of elemene were added before the injury. After
      culturing 1 hour, then detecting the index of MDA, T-AOC, SOD, CAT, GSH-Px and
      NO. RESULTS: Elemene could inhabit the proliferation of VEC and it presented dose
      dependent, while on the side of anti-oxidization injury, it also presented dose
      dependent. MDA content and the effect of H2O2 to antioxidase activity were
      decreased, NO content in cell was increased, and the amount of apoptosis was
      reduced. CONCLUSION: Elemene has dual effects on the survival rate of normal
      HUVECs in vitro, which is related to the concentration and the duration of drug
      exposure. Elemene has protective effects on the injured endothelial cells injured
      by oxidization through the function of anti-lipid oxidization.

PMID- 18323211
TI  - [Beneficial effects of Qiangxin capsule on controlling protein expression of
      myocardial apoptosis in heart failure rats].
AB  - OBJECTIVE: To observe the effects of Qiangxin Capsule on myocardial apoptosis in
      chronic heart failure rats. METHODS: The model was established by injecting ADR
      in intraperitoneal of Wistar rat. The models were devided into three groups those
      were prvention group with Chinese medicine, treatment group with Chinese medicine
      and control group with medicine. Cardiac myocyte apoptosis were detected by
      terminal deoxynucleotidyl transferaseediated dUTP nick-end labeling (TUNEL), Fas
      and cardiac expression level of Bcl-2 were detected by immunohistochemistry.
      RESULTS: Qiangxin capsule could inhibit myocardial apoptosis and Fas protein
      expression on chronic heart failure rat obviously , and improve Bcl-2 protein
      expression. CONCLUSION: Qianxin capsule can inhibit myocardial apoptosis and
      control Fas/Bcl-2 obviously. It may be one of its effects in delaying chronic
      heart failure.

PMID- 18323212
TI  - [Erythrocyte immunologic function effects of Patrinia scabra extracts by
      macroporous adsorptive resins on mice burdened transplanted tumor].
AB  - OBJECTIVE: To research the erythrocyte immunoregulation effects of Patrinia
      scabra extracts by macroporous adsorptive resins on mice burdened transplanted
      tumor. METHODS: Extracts of Patrinia scabra Bunge were separated by macroporous
      adsorptive resins, ingredients were analysised. Mice burdened transplanted tumor
      were given extracted drugs. Life prolongation rate was observed, erythrocyte
      immunologic function and the CD35, CD44s contents of red blood cell were
      evaluated. RESULTS: Polysaccharide and saponin accounted for 8.4% and 48.4%.
      Extracts could porolong life expectancy of mice, improve erythrocyte immunolgic
      function and increase the CD35 and CD44s contents of red blood cell. CONCLUSION:
      Extracts of Patrinia scabra Bunge by macroporous adsorptive resins have
      erythrocyte immunoregulation effects on mice burdened transplanted tumor.

PMID- 18323213
TI  - [Study of antitumous effect of the complex prescription of Chinese crude drug in
      athymic mice with HCC].
AB  - OBJECTIVE: To research the treatment effect of a complex prescription of Chinese
      crude drug in BALB/c athymic mice. METHODS: 48 male BALB/c athymic mouse models
      were built by Bel-7402 with an indirect method. After 24 hours of postoperation,
      they were distributed randomly into 4 groups which were treated by intragastric
      administration with complex prescription of Chinese crude drug of different
      density as the low, middle, high and FF207 (Tegafur) for 4 weeks. At last,
      athymic mice were put to death and survial time, volume of tumors, exponent of
      tumors and the tumor metastasis in livers were observed; and PTEN was detected in
      hepatic tissue, latero-cancer tissue and cancer tissue by immunohistochemistry.
      RESULTS: 4 weeks later, the total survival rate in treatment group (A + B + C)
      was 50% and more higher than the control group (0%) treated by FT207, P < 0.01.
      The survival rate in group A, B, C was higher than group D, except group A, there
      was significant differences, P < 0.05 or 0.01. And no differences were observed
      between the treatment groups and the control group in volume of tumors and
      exponent of tumors, P > 0.05. Tumor metastasis in livers of the treatment group
      is less than the control's, P < 0.05. Negative correlation between volume of
      tumors and survival time, positive correlation between tumors volume and spleen
      exponent were observed, P < 0.01. The result of immunohistochemistry represented
      that the intensity of PTEN in latero-cancer tissue was the highest, and then the
      hepatic tissue, the lowest was cancer tissue, P < 0.01. It also represented that
      the intensity of PTEN in treatment groups (A, B, C) was more higher than the
      control group (D), and group B was the highest in the treatment groups, P < 0.05
      or P < 0.01. However, there was no significant statistic difference between group
      A and group C, P > 0.05. CONCLUSION: This complex prescription of Chinese crude
      drug can prolong the survival time and decrease tumor metastasis in livers of
      these experimental mice. Too large tumor volume is an main death cause of model.
      Mechanisms of this complex prescription of Chinese crude drug healing HCC may
      partially be explained by enhancing the expression of PTEN in liver.

PMID- 18323214
TI  - [The study of therapeutic effects of curcumin on hepatic fibrosis and variation
      of correlated cytokine].
AB  - OBJECTIVE: To investigate therapeutic effects of curcumin on hepatic fibrosis and
      the variation of correlated cytokine. METHODS: Rat models of hepatic fibrosis
      were made by carbon tetrachloride. Curcumin of 10, 20, 40 mg per 100 gram weight
      of rat were given to these rats of curcumin group respectively from ninth week.
      Normal, dissolvent, model and Salvia miltiorrhiza groups were made as controls.
      Serum levels of ALT, AST, HA, LN, PC-III were detected; Serum levels of TGF-beta1
      and TNF-alpha were detected by ELISA method; Serum levels of NO were detected by
      chemical method. HE and Masson staining were conducted in hepatic tissues to
      observe pathological variations. Grades of hepatic fibrosis were evaluated
      according to SSS system. Immunohistochemical staining was executed for detecting
      PDGF-BB in liver, and professional software for image analysis was used. RESULTS:
      Curcumin could decrease serum levels of ALT, AST, HA, LN, PC-III obviously, P <
      0.05, which were increased in fibrotic group. Curcumin could decrease cytokine
      levels of NO, TGF-beta1, TNF-alpha, P < 0.05. Curcumin could obviously improve
      liver pathological variations of fibrotic rats. The score of hepatic fibrosis in
      curcumin group reduced significantly, P < 0.05. Curcumin treatment could reduce
      the expression of PDGF-BB, P < 0.05. These effects were dose-dependent.
      CONCLUSION: Curcumin can heal rat hepatic fibrosis. Effects of reducing the
      expression of correlated cytokines may be mechanisms of therapeutic effects of
      curcumin on hepatic fibrosis.

PMID- 18323215
TI  - [Toxicity attenuation and efficacy potentiation effects of Fu Zheng Yang Yin
      Decoction with HIFU on the experimental model of VX2 cancer in rabbits' liver].
AB  - OBJECTIVE: To investigate the toxicity attenuation and efficacy potentiation
      effects of Fu Zheng Yang Yin Decoction with HIFU on the experimental model of VX2
      liver cancer in rabbits. METHODS: The rabbits were all transplanted with VX2
      cancer on livers. The 30 rabbits were divided into three groups: HIFU group (HIFU
      therapy), Combination group (HIFU + Fu Zheng Yang Yin decoction), Control group
      (without any treatment). Each group involved 10 rabbits. After treatment, the
      volume of the tumor was observed by sonography. Metastases, pathological changes,
      Immunoglobulin, ALT were also observed. RESULTS: After treatment, ALT and
      temperature of Combination group and HIFU group were lower than Control group (P
      < 0.05). The tumor volume of Combination group and HIFU group showed significant
      difference with control group (P < 0.05). Immunoglobulin of HIFU group and
      Combination group increased, that of Control group decreased. One month after
      treatment, all animals were dissected. Combination group had no lung transferred,
      HIFU group had 2 lung transferred, all of control group had lung transferred.
      CONCLUSION: The combination therapy of Fu Zheng Yang Yin decoction with HIFU can
      effectively inhibited VX2 cancer growth in rabbit's liver. Fu Zheng Yang Yin
      decoction can reduce side-effect, improve immune function, and has special
      effects of toxicity attenuation and efficacy potentiation.

PMID- 18323216
TI  - [Optimization of water extraction condition of LiYan granule by Doehlert design].
AB  - OBJECTIVE: To study optimal water extraction condition of LiYan granule. METHODS:
      HPLC methods were developed for the determination of irisfloremin in LiYan
      granule. The contents of irisfloremin and extraction rate were selected as
      assessment indices. Three factors were studied by Doehlert design, including
      water-adding amount, decoction time and times of decoction. RESULTS: The optimal
      extracting condition was water consumed as 8 times of curd herb, and 3 times for
      2 hours each time. CONCLUSION: The water extraction process is feasible, and the
      experiment result can provide basic and instruction data for the ascertainment of
      water extraction process of LiYan granule.

PMID- 18323217
TI  - [Research on method in avoiding the interference of poloxamer in determination of
      polysaccharides in thermosensitive gel].
AB  - OBJECTIVE: To study a method in avoiding the interference of poloxamer in
      determination of polysaccharides in thermosensitive gel and develop an assay
      correspondingly. METHODS: After extracting the freeze dried gel with acetic
      ether, detected it in colorimetric method. RESULTS: The interference of poloxamer
      was removed thoroughly, while the retention rate of the polysacchrarides showed
      to be 100.11% (n = 3). The average recovery was 102.6% (n = 6). CONCLUSION: The
      method shows to be simple, maneuverable, stable and well reproducible.

PMID- 18323218
TI  - [Study of quality control on Cuscuta chinensis and C. australia].
AB  - OBJECTIVE: To study the estimate method of C. chinensis and C. australia. METHOD:
      HPLC was used to determine the contents of four kinds of flavones of C. chinensis
      and C. australia growing on different hosts. RESULT: C. chinensis and C.
      australia growing on different hosts both had hyperoside, quercetin, kaempferol
      and isorhamnetin. The content range of hyperoside was 2.790-6.502 mg/g and was
      higher than other flavones. The content ranges of quercetin, kaempferol and
      isorhamnetin were 0.025-0.176 mg/g, 0.001-0.213 mg/g and 0.001-0.077 mg/g,
      respectively. CONCLUSION: The contents of hyperoside and quercetin are higher in
      C. chineasis than in C. australia. The contents of kaempferol and isorhamnetin
      are lower in C. chinensis than in C. australia. The hosts influence flavones
      content of C. chinensis and C. australia.

PMID- 18323219
TI  - [Improvement on microwave technology of extracting polysaccharide from yacon
      leaves].
AB  - According to the extraction ratio of polysaccharide in yacon leaves, the
      comparison between microwave extraction and traditional hot water extraction was
      conducted, and the two-factor and three-level experiment on the microwave
      extraction of polysaccharide from yacon leaves was investigated. The result
      showed that the extraction ratio of polysaccharide by using microwave extraction
      was better than that by using traditional hot water extraction. Moreover,
      according to the result of variance analysis and multiple comparison, the optimum
      conditions for extraction of polysaccharide by using microwave technology from
      yacon leaves were as follows: 280W microwave power for 2 times and 15 minutes at
      every time.

PMID- 18323220
TI  - [Preparation of alpha-hydrocycholic-beta-cyclodextrin inclusion compound].
AB  - OBJECTIVE: To study the preparation of alpha-Hydrocycholic-beta-Cyclodextrin
      inclusion compound. METHODS: It was studied with orthogonal design to analysis
      three factors of inclusion rate such as the weight ratio between HDCA and beta
      Cyclodextrin, the temperature and the reaction time. Fourier transform infrared
      spectroscopy, scanning electron microscopy, taste and solubility test were used
      to identify the inclusion compound. RESULTS: Stable inclusion compound was made
      by HDCA and beta-Cyclodextrin. The weight ratio between HDCA and beta
      Cyclodextrin was the most important factor. The alpha-Hydrocycholic-beta
      Cyclodextrin inclusion compound taste and the solubility were improved.
      CONCLUSION: The optimum preparation condition is alpha-Hydrocycholic : beta
      Cyclodextrin = 8.67 : 1, the inclusion temperature is 60 degrees C and the
      inclusion time is 30 minutes.

PMID- 18323221
TI  - [Supercritical coupling traditional way to extract flavones in Saussurea
      involucrate].
AB  - The Saussures involucrate was pretreated with supercritical CO2, then the residue
      was extracted with ethanol. Using a method of orthogonal experiment, the
      influence of temperature, time, liquid/solid ratios, the concentration of ethanol
      to the total flavones content were investigated. Compared with traditional
      extraction method, about more than 10.07%-128.4% flavones were obtained. In
      conclusion, the supercritical coupling traditional way could enhance the
      extraction efficiency, lower the extraction temperature, shorten the lixiviating
      time, reduce the losing of effective component, and pre-extract the plants
      (obtain about 2.45% oil segment). The study developed a new application of
      supercritical technology in the extraction of natural resources.

PMID- 18323222
TI  - [Chemical contrast research on Buyang Huanwu complex ultramicro powder soak and
      traditional decoction].
AB  - OBJECT: To study the chemical composition of Buyang Huanwu complex ultramicro
      powder soak and traditional decoction. METHODS: Extractive determination, heavy
      metal and arsenic determination, TLC and HPLC were used to analysis the chemical
      composition. RESULTS: The extract of Buyang Huanwu complex ultramicro powder soak
      was higher than that of traditional decoction. The lamellar spot of Buyang Huanwu
      complex ultramicro powder soak was clearer than that of traditional decoction.
      Astragalin in Buyang Huanwu complex ultramicro powder soak was correspond with
      the traditional decoction. CONCLUSION: The way of soaking ultramicro powder not
      only can avoid losing active component, but also can release it quickly.

PMID- 18323223
TI  - [Clinical observation of modified Suan Zao Ren decoction on insomnia of chronic
      hepatitis B patients].
AB  - OBJECTIVE: To explore the effect of modified Suan Zao Ren Decoction (mediation
      decoction) on insomnia of chronic hepatitis B patients with stagnation of the
      Liver-Qi and deficiency of blood syndrome. METHODS: Sixty-five patients of
      chronic hepatitis B with stagnation of the Liver-Qi, deficiency of the spleen and
      damp-heat syndrome were randomly divided into two groups. Thirty-three patients
      in the treatment group were treated by modified Suan Zao Ren Decoction, and
      thirty-two patients in the control group were treated by Surazepam and Diammonium
      Glycyrrhizinate. The clinical syndromes of insomnia and liver function were
      observed before and after treatment. RESULTS: After one months of treatment, the
      main symptoms and signs of insomnia are improved in both groups, stage I and II
      sleep decreaed significantly while stage Il, IV and rapid eye movement increased
      in insomniacs after treatment of modified Suan Zao Ren Decoction (P < 0.05). The
      total effective rate was not significantly different between the two groups (P >
      0.05), while the markedly effective rate was significantly different (P < 0.05).
      In the same time, ALT, AST, TB levels of two groups were obviously decreased (P <
      0.01, P < 0.05), AST levels of two groups after treatment were significant
      different (P < 0.05). CONCLUSION: Modified Suan Zao Ren Decoction is effective
      for improving sleep composition, and therefore improve the quality of sleep with
      few side effect. In the same time, it has the function in improving liver
      function, and can be used to treat chronic hepatitis B patients with insomnia.

PMID- 18323224
TI  - [Aurel Nana].

PMID- 18323225
TI  - Abdominal compartment syndrome: effects on organ function.
AB  - Abdominal compartment syndrome (ACS) constitutes a critical clinical situation
      presenting a remarkable incidence being the causal factor of variable abdominal
      and extra-abdominal pathology, thus a rising issue of interest in intensive
      medical care over the past decade. Moreover, ACS as a condition potentially
      leading to Multiple Organ Failure (MOF), its better understanding could provide
      more effective management resulting to limitation of MOF incidence and mortality.

PMID- 18323226
TI  - [Risk factors for malignant evolution of gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumors are the most frequent non-epithelial digestive
      tumors, being classified in the group of primitive mesenchymal tumors of the
      digestive tract. These tumors have a non predictable evolution and where
      stratified regarding the risk for malignant behavior in 4 categories: very low
      risk, low risk, intermediate risk and high risk. We performed a retrospective non
      randomised study including the patients with gastrointestinal stromal tumors
      treated in the Department of General Surgery and Liver Transplantation of Fundeni
      Clinical Institute in the period January 2002 - June 2007, to define the
      epidemiological, clinico-paraclinical, histological and especially evolutive
      features of the gastrointestinal stromal tumors from this group, with a special
      regard to the risk factors for their malignant behavior. The most important risk
      factors in gastrointestinal stromal tumors are the tumor size and the mitotic
      index, based on them being realised the classification of Fletcher in the 4 risk
      categories mentioned above. In our group all the local advanced or metastatic
      gastrointestinal stromal tumors, regardless of their location, were classified in
      the group of high risk for the malignant behavior. The gastric location and the
      epithelioid type were positive prognostic factors, and the complete resection of
      the tumor, an other important positive prognostic feature, was possible in about
      80% of the cases, probably because the gastrointestinal stromal tumors in our
      study were diagnosed in less advanced evolutive situations, only about one third
      being metastatic and about 14% being locally advanced at the time of diagnose.
      The association with other neoplasias was in our cases insignificant, only 5% of
      the patients presenting concomitant malignant digestive tumors and 7.6%
      intraabdominal benign tumors. Gastrointestinal stromal tumors remain a challenge
      for the medical staff, regarding their diagnose and therapeutical management, the
      stratification of the risk for their malignant behavior being essential for the
      evolution of these patients.

PMID- 18323227
TI  - [Pancreaticoduodenectomy with or without pylorus preservation: a retrospective
      analysis of 137 patients].
AB  - OBJECTIVE: We performed a retrospective study to assess the postoperative
      results, long-term survival and quality of life after pylorus preserving
      pancreaticoduodenectomy (PPPD) versus standard Whipple pancreaticoduodenectomy
      (WPD). METHODS: A retrospective study was performed in a nonselected series of
      137 patients who were operated in the Surgical Clinics of "St. Spiridon"
      University Hospital Iasi, Romania, from January 1st, 1995 till December 31, 2005.
      Demographics, preoperative and intraoperative data, as well as postoperative
      morbidity, mortality and follow-up were analyzed. Quality of life, after to at
      least six months after discharge, was also studied. RESULTS: There were no
      significant differences noted in demographics data. Jaundice was more frequent in
      the PPPD group as for WPD patients (p=0.047). For the most patients the digestive
      reconstruction after resection were performed as in Child technique: the first
      anastomosis was pancreaticojejunostomy (end-to-end or end-to-side), the second
      anastomosis was hepaticojejunostomy (end-to-side) and the last anastomosis was
      gastrojejunostomy end-to-side (duodenojejunostomy in PPPD group). For 31 cases a
      pancreatico-gastrostomy were performed. We also noted 14 cases with pancreatico
      gastrostomy and duodenojejunostomy end-to-end, and a Roux jejunal loop for 3
      patients with previous gastrectomy and gastrojejunostomy (Reichel-Polya). The
      operating time was shorter in the PPPD group as in WPD (p < 10-3), but the mean
      blood loss was the same. Postoperative morbidity rate was 46.8% in PPPD group vs
      39.2% in WPD (p > 0.05), but the reintervention rate was significant higher in
      PPPD group (30.6% vs 15%; p = 0.027). We also noted no significant differences of
      Delayed Gastric Emptying, postoperative mortality rate (14.5% in PPPD group vs
      10.1% in WPD group) and mean survival time (42.42 months (24.94 - 59.89; 95% CI)
      in PPPD group vs 46.78 months (28.07 - 61.50; 95% CI) in WPD group; log rank test
      p = 0.643). Pathological exam diagnosed a malignancy in 109 cases (54 cases with
      pancreatic cancer); we noted chronic pancreatitis in 22 cases. Quality of life
      was also the same in the two groups. CONCLUSIONS: PPPD and WPD were associated
      with comparable results, but, there is a tendency of increase rate of
      postoperative morbidity and mortality for PPPD patients. We also noted that
      postoperative quality of life is the same for both procedures.

PMID- 18323228
TI  - [Spleno-renal distal and proximal shunts for hypersplenism due to hepatic
      cirrhosis].
AB  - The secondary hypersplenism appears from 30-50% in liver cirrhosis with portal
      hypertension. The mechanism of the complication is the splenic congestion as the
      result of the progress of the portal hypertension. Between 1997-2005, 16 patients
      with hypersplenism due to liver cirrhosis were operated in the service. The aim
      of the operation was to decompress the portal hypertension, by spleno-renal shunt
      (Warren), in 6 patients, truncular shunts in 2 patients, and splenectomy with
      spleno-renal shunts in 8 patients. No postoperative death was noted on the
      series. The platelets number and the white blood cells, destroyed by the
      reticuloendothelial system of the spleen, were counted in the first month and the
      first year, as well as the spleen volume. In patients with non-splenectomy
      operations the improvement of the blood elements number was remarked in the first
      week, but the volume of the spleen remained increased during 1-6 month. In
      patients with splenectomy the platelets and the white cells dramatically
      increased, with the risk of coagulation disfunction. The survival rate at five
      years was 12 patients.

PMID- 18323229
TI  - [Laparoscopic cholecystectomy in an overnight admission].
AB  - OBJECTIVE: to determine the feasibility and desirability of laparoscopic
      cholecystectomy (LC) in an overnight versus a several day admission. BACKGROUND:
      Although LC is performed in U.S.A. as outpatient surgery this has not been
      generally accepted in Europe. The main objections, are the risk of complications
      becoming apparent at home. Considering the specific local conditions and the
      general attitude towards early discharge we tried to assess the degree of
      feasibility and acceptance of a overnight admission in our patients. METHODS: Two
      groups of forty patients each, with symptomatic gallstones, received LC either in
      an overnight or a several day admission. Preoperative and intraoperative data and
      postoperative recovery were prospectively assessed. RESULTS: The general and
      female age, the duration and frequency of the biliary pain, the duration and the
      degree of difficulty of the operation and the necessity of the subhepatic
      drainage were all significant in favour of the group with a shorter stay. No
      postoperative complications were recorded. CONCLUSIONS: Overnight LC is safe and
      effective in treating patients requiring LC. The option of the patient must also
      be considered.

PMID- 18323230
TI  - A comparison of sevoflurane-fentanyl and neuroleptic anaesthesia for laparoscopic
      cholecystectomy of mildly obese patients.
AB  - The current study was formulated to evaluate the advantages and disadvantages of
      sevoflurane-fentanyl and neuroleptic anaesthesia for laparoscopic cholecystectomy
      surgery of mildly obese patients. Laparoscopic cholecystectomy was performed
      using either sevoflurane-fentanyl or neuroleptic anaesthesia. Intra-operative
      haemodynamic stability, surgical duration, awakening time, severity of post
      operative pain and hormonal stress parameters (serum and urinary cortisol, serum
      insulinlike growth factor and serum insulin) were determined. The duration of
      both surgery and patient hospitalisation were similar in both study groups.
      Patients that received sevoflurane-fentanyl exhibited a significantly shorter
      awakening time compared to neuroleptic anaesthesia. In addition, the same group
      of patients had less post-operative complications (nausea, vomiting, urinary
      retention and respiratory insufficiency) despite more abdominal pain. The
      severity of postoperative pain and the requirement of additional analgesia (up to
      12 hours post-surgery) were greater in patients that received sevoflurane
      fentanyl. The serum and urinary cortisol concentrations were significantly
      increased in post-operative patients that received neuroleptic anaesthesia
      whereas the insulin-like growth factor-I concentration in both study groups
      significantly decreased post-operatively. Our results clearly show that
      neuroleptic anaesthesia attenuates the stress response to laparoscopic
      cholecystectomy to a lesser extent than sevoflurane-fentanyl. The latter
      anaesthesia is recommended for laparoscopic cholecystectomy of mildly obese
      patients.

PMID- 18323231
TI  - [Surgical and anesthetic coordination during tracheal and carinal resections and
      reconstruction].
AB  - A retrospective study of anesthetic and surgical techniques involved in 55
      consecutive cases of tracheal and carinal resections completed from 2001 to 2007,
      is presented. The anesthetic maneuvers and surgical approach differed in relation
      with the site of the tracheal lesions (upper, middle, lower trachea or carinal),
      the degree of the obstruction, the emergency of the surgical intervention and the
      concomitant presence of the eso-tracheal fistula. Ventilatory support during
      anesthesia involved special equipment adapted to the particular techniques used
      in this type of surgery. Cross field intubation of trachea or a mainstem
      bronchus, and High Frequency Jet Ventilation-HFJV- have been frequently used.
      Perfect coordination of the anesthetic techniques with every surgical step is
      mandatory and for good long term results special anesthetic equipment and a good
      preoperative anesthetic and surgical assessment of the strategy is needed.

PMID- 18323232
TI  - [Hypospadias surgery--etiology of complications].
AB  - INTRODUCTION & OBJECTIVE: Hypospadias surgery carries a hole list of precocious
      and late complications which may occur even years later after surgery such as a
      very late fistula or a recurrent chordee. The aim of this article was to
      investigate the reasons, why a significant number of patients with different
      types of hypospadias presents the same kind of postoperative complications.
      MATERIALS AND METHODS: Records of 51 boys who underwent surgery for different
      types of hypospadias were reviewed. Primary repair was performed in 41 patients.
      12 (29.4%) of them had postoperative complications. 10 boys had previously
      between 1 to 7 repairs. The complications were those mentioned in the literature
      (fistulas, stenoses, megalo-urethra and relapse of the ventral curvature). The
      etiology of the complications was evaluated according to the type of hypospadias,
      the surgical technique used for the initial corrective surgery and postoperative
      care. RESULTS: The original malformation had been miss-classified in 10% of the
      cases; technical mistakes occurred in 70% of the cases; complications derived
      from the complexity of the repair procedure were documented in 10% of the cases,
      and in 10% of the cases the cause was complex: technical and postoperative care
      mistakes. CONCLUSIONS: Complications after hypospadias surgery appears due to
      five main reasons which usually coexist. In order to prevent complications, an
      accurate classification must be made, the surgical procedure has to be chosen
      accordingly, the surgical technique must be perfect and the postoperative care
      adequate.

PMID- 18323233
TI  - [Stress urinary incontinence. Diagnostic and therapeutic aspects].
AB  - OBJECTIVE: The paper analyses the incidence, diagnosis and treatment options
      available for stress urinary incontinence (SUI) in women with pelvic floor
      dysfunction admitted to Craiova's Surgery Clinic IV. METHODS: This is a
      retrospective 10-year study comprising a surgical cohort of 420 patients with
      significant enough to alter quality of life SUI associated to ureterocele and
      cystocele and in 353 cases with rectocele too. The highest incidence of SUI was
      encountered between 50 and 59 years of age (range 39 - 81 years). In 21 of this
      case series the diagnosis of SUI was established soon after the surgical repair
      of the urethro-cystocele. The diagnosis of SUI was based on careful history and
      physical examination with emphasis on the gynecologic survey of the abdomen and
      pelvis but in the absence (for objective reasons) of urodynamic testing which is
      especially useful for SUI pathophysiological evaluation and thus surgery success
      rate prediction. All our 420 severe SUI associated with vaginal wall hernias
      underwent surgical treatment by either open Burch retropubic urethropexy or
      anterior colporraphy. RESULTS: Among anterior colporraphy treated patients SUI
      persisted in 19.3% of the cases (33 patients). Complications of Burch urethropexy
      procedure (despite its high ability for cure) in our case series include: urinary
      retention, hemorrhage into the space of Retzius, intraoperative injury to the
      bladder and long-term postoperative incisional hernia. Moreover, 5 patients (2%)
      of the group who underwent Burch operation were readmitted with recurrent urinary
      incontinence between 2 and 6 months after the aforementioned surgical
      intervention despite its good anatomical results in all of these cases.
      CONCLUSIONS: SUI is a prevalent disorder of women that can be diagnosed easily
      with history and physical exam. If symptoms persist and severely affect quality
      of life, despite modern noninvasive treatments, several surgical procedures are
      now available.

PMID- 18323234
TI  - [Foreign bodies in the urogenital tract--between iatrogeny and autoerotism].
AB  - INTRODUCTION: Our objective was to evaluate the cause, diagnosis and management
      of foreign bodies in the urogenital tract reviewing a 7 years experience.
      MATERIALS AND METHODS: From 2000 to 2007, 12 patients were treated in our
      department because of foreign bodies localized in the urogenital tract. We
      retrospectively analyzed the data regarding presentation, diagnosis and
      management. RESULTS: The foreign bodies from the urogenital tract included:
      mascara, spray cap, wires, candle, swabs, plastic tube, remnants from JJ ureteral
      stent and nefrostomy tube. Diagnostic investigations varied from case to case and
      consisted of: KUB (kidney, ureter and bladder), abdominal ultrasound, urography,
      computer tomography, and also cystoscopy. The management was endoscopic in 4
      (33%) cases, but in the great majority of them--8 (67.6%) it was necessary a
      classical intervention. CONCLUSIONS: Foreign bodies localized in the urogenital
      tract, represents a relative rare pathology and in many situations those cases
      have legal implications. Investigations must include radiologic investigations in
      order to identify their exact location and size. In many cases the management can
      not be endoscopic and it is necessary a classic intervention.

PMID- 18323235
TI  - [Antiperistaltic esophagoplasty with left colon].

PMID- 18323236
TI  - [Treatment of generalized appendicular peritonitis. Drainage of pelvic and
      subhepatic space. 1930].

PMID- 18323237
TI  - [Malignancy of familial adenomatous polyposis. Diagnosis and treatment].
AB  - Familial adenomatous polyposis with features of malignancy find in a 23 years old
      patient, whose diagnosis has been established on endoscopical basis. Total
      proctocolectomy is performed with terminal ileostomy. Histopathologically, the
      diagnosis is revealed, with establishing of multiple areas of malignancy in
      rectum and sigmoid colon. In the postoperative period, the patient is treated by
      pelvic radiotherapy and polychemotherapy. After one year, the clinical outcome is
      good, with weight gain 13 Kg and finishing high school. After two years,
      peritoneal carcinomatosis and one lung metastasis.

PMID- 18323238
TI  - [Gastrojejunocolic fistula--a rare complication of stomach surgery].
AB  - The gastrojejunocolic fistula represents a clinical entity that occurs very
      rarely following gastro-jejunal anastomoses and manifests itself clinically and
      paraclinically by a severe malabsorption syndrome. The results of the
      physiopathological approach may be summed up as follows: reduced level of seric
      proteins, fluid and electrolytic depletion, deficiencies in the absorption of the
      vitamins soluble in fats and water, which may all vary from mildness to
      severeness, depending on the flow rate of the fistula. Most often, the diagnosis
      is set by performing barium enema, which is positive for all cases, whereas the
      barium passage is less efficient, enabling diagnosis in only 33% of the cases.
      The radiological image may be reduced on principle to one single sign: the
      abnormal fistulous trajectory (barium passes from the stomach directly into the
      colon or the enema fills the gastric lumen). It is recommended that surgical
      treatment be performed in a single stage, by resecting the entire fistula and re
      establishing the gastro-jejunal and colic continuity. We report a case of
      gastrojejunocolic fistula in a patient that underwent 2/3 gastric resection for
      gastric ulcer 9 years ago.

PMID- 18323239
TI  - [An unusual splenic tumor. Littoral cell angioma].
AB  - Littoral cell angioma is a rare splenic tumor which develops from specialised
      endothelial cells of the splenic red pulp. Numerous papers published since 1991
      when the tumor was firstly described till now were focused on the radiologic
      characteristics of the lesion. This paper presents the clinical, imaging and
      morpho-immunohistochemical features of a littoral cell angioma diagnosed in a 51
      year - old woman, to our knowledge, the first documented case in the Romanian
      medical literature. The lesion might be suspected on the basis of the clinical
      and imaging signs, but the diagnosis of certitude is provided by the gross and
      microscopic examination supplemented with immunohistochemical methods.

PMID- 18323240
TI  - Spectroscopic study of hexahydroquinoline derivatives--a potential group of
      calcium antagonists.
AB  - Spectral properties of 2, 6, 6-trimethyl-3-carbmethoxy-4-phenyl-5-oxo 
      1,4,5,6,7,8-hexahydroquinoline derivatives (HHQ) with different substituents in
      the phenyl ring (-Cl, -NO2, -CF3, -CH3, -OCH3) have been studied. Their emission
      and absorption spectra have been analyzed and quantum yields of emission were
      determined. The quantum yield of emission was found to depend on the kind,
      number, and position of substituents in the phenyl ring: it was the highest for
      the chlorine derivatives of HHQ, and the lowest for the compounds containing -NO2
      group.

PMID- 18323241
TI  - The research on Antoxid activity in free radicals processes.
AB  - The joint effect of Antoxid (AX), extract from Radix Scutellariae baicalensis,
      with vitamin C on ferric reducing human plasma ability (FRAP) was examined. In
      order to explain the mechanism of Antoxid inhibiting effect on lipid peroxidation
      stimulated by xylene, its influence on hydroxyl radical generation was examined.
      The preventing and repairing effect of Antoxid was evaluated towards the lipid
      peroxidation stimulated with xylene by treatment before or after exposition. The
      results showed that the various combinations of Antoxid with vitamin C possessed
      antioxidative properties, but the significant synergistic effect was noted for
      weight ratio 1:1 of Antoxid and vitamin C in concentration 5 microg/mL. Antoxid
      didn't decrease the hydroxyl radicals level produced by xylene. Both preventing
      and repairing effect of Antoxid in oxidative stress caused by xylene is not
      connected with hydroxyl radical scavenging.

PMID- 18323242
TI  - Ameliorative effect of curcumin on aflatoxin-induced toxicity in DNA, RNA and
      protein in liver and kidney of mice.
AB  - The present investigation is an attempt to evaluate the ameliorative effect of
      curcumin on aflatoxin-induced toxicity in liver and kidney of mice. Aflatoxin was
      obtained by growing Aspergillus parasiticus in SMKY liquid medium. 70 male mice
      were divided into 7 groups (37-40 g body weight) including untreated control,
      vehicle control (0.2 mL olive oil/animal/day), curcumin control (50 mg/kg body
      weight/animal), aflatoxin low dose and high dose (750 and 1500 mg/kg body
      weight). Other two groups were administered curcumin along with low dose
      aflatoxin and high dose aflatoxin. The treatment was given for 45 days. On 46th
      day the animals were sacrificed by cervical dislocation. Liver and kidney were
      removed and weighed. Homogenates were prepared and analyzed for DNA, RNA and
      protein content. The results revealed dose-dependent significant reduction in
      DNA, RNA and protein contents in the liver and kidney of mice. Oral
      administration of aflatoxin along with curcumin significantly ameliorates, as
      compared to aflatoxin alone treated groups, in all parameters. It is concluded
      that curcumin ameliorates aflatoxin-induced toxicity in liver and kidney of mice.

PMID- 18323243
TI  - Interactions in free radicals processes between cyclosporine A and sodium
      fluoride.
AB  - The interactions in free radicals processes between cyclosporine A (CsA) and
      sodium fluoride (NaF) on in vitro model human placental mitochondria were
      evaluated. The level of malondialdehyde, hydroxyl radical generation and
      concentration of sulfhydryl groups of protein was measured. The results showed
      that CsA with NaF did not give any toxicological interactions with NaF in the
      area of measured parameters.

PMID- 18323244
TI  - Synthesis of a phenylalanine-rich peptide as potential anthelmintic and cytotoxic
      agent.
AB  - A natural cyclic heptapeptide segetalin D [VIII] was synthesized by coupling of
      tripeptide unit Boc-Pro-Gly-Leu-OMe [V] with tetrapeptide unit Boc-Ser-Phe-Ala
      Phe-OMe [VI] after proper deprotection at carboxyl and amino ends followed by
      cyclization of linear peptide segment. Structure of VIII was confirmed by
      spectral and elemental analyses. The newly synthesized cyclopeptide was tested
      for its antibacterial, antifungal, anthelmintic and cytotoxic activities.
      Compound VIII showed high cytotoxicity against Dalton's lymphoma ascites (DLA)
      and Ehrlich's ascites carcinoma (EAC) cell lines with CTC50 values of 7.54 and
      13.56 microM. Moreover, VIII exhibited potent anthelmintic activity against
      earthworms Eudrilus species, Megascoplex konkanensis and Pontoscotex corethruses
      at a dose of 2 mg/mL.

PMID- 18323245
TI  - Optimization of some physical and nutritional parameters for the production of
      hyaluronidase by Streptococcus equi SED 9.
AB  - The effects of some physical and nutritional parameters were studied for the
      optimum production of an extracellular enzyme hyaluronidase employing
      Streptococcus equi SED 9 by submerged fermentation. The effects of initial pH,
      incubation temperature and time, inoculum level and age of inoculum were studied.
      The maximum enzymatic activity was obtained with an initial pH 5.5, incubation
      temperature 37 degrees C, incubation time for 48 h and inoculum level 10% with
      inoculum age 48 h. The effects of various carbon and inorganic nitrogen sources,
      vitamins, amino acids and growth hormones were studied. The results indicated
      that dextrose, ammonium sulfate, nicotinic acid, L-cysteine and kinetin showed
      the highest enzymatic activity among them.

PMID- 18323246
TI  - Synthesis of aminoalkanol derivatives of 4-hydroxy-1,7,8,9,10-pentamethyl-4-aza
      tricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione as potential beta-adrenolytics.
AB  - A series of aminoalkanol derivatives of 4-hydroxy-1,7,8,9,10-pentamethyl-4-aza
      tricyclo[5.2.1.0(2,6)]dec-8-ene-3,5-dione have been prepared. The pharmacological
      profile of selected compounds was evaluated for their affinities at beta
      adrenoreceptors.

PMID- 18323247
TI  - Synthesis and preliminary evaluation of aminoalkanol derivatives of selected
      azatricycloundecane system for binding with beta-adrenergic and 5HT1A and 5HT2A
      receptors.
AB  - A series of aminoalkanol derivatives of 8,11-dimethyl-3,5-dioxo-4
      azatricyclo[5.2.2.0(2,6)] undec-8-en-1-yl acetate and 1,11-dimethyl-4
      azatricyclo[5.2.2.0(2,6)]undecane-3,5,8-trione was prepared. The pharmacological
      profile of selected compounds was evaluated for affinity to beta-adrenoreceptors
      and serotoninergic receptors (5HT1A and 5HT2A).

PMID- 18323248
TI  - Synthesis of 1-{4-[4-(adamant-1-yl)phenoxymethyl]-2-(4-bromophenyl)- 1,3-dioxolan
      2-ylmethyl}imidazole with expected antifungal and antibacterial activity.
AB  - A multistep synthesis of a new analogue of ketoconazole, which was expected to
      show antifungal and antibacterial activity, has been described.

PMID- 18323249
TI  - Pharmacognosy and hypotensive evaluation of Ficus exasperata Vahl (Moraceae)
      leaf.
AB  - There is already a literature report on the anti-ulcer effect of water extract of
      Ficus exasperata. Some communities in Edo and Delta States of Nigeria use the
      decoction of the leaf as hypotensive crude drug. Verification of this claim and
      also the microscopy and other pharmacognostic parameters which can be used to
      establish the identity of the leaf were carried out. The microscopy of the leaf
      powder revealed the presence of straight walled epidermal cells, cone or nail
      shaped trichomes or epidermal hairs, clustered or prismatic calcium oxalate
      crystals of varying dimensions. The percentage weight loss on drying was 9.84 +/-
      0.08 whereas water and alcohol extractive values were 5.29 +/- 0.07 and 2.21 +/-
      0.11, respectively. The ash value was 30.68 +/- 0.44 whereas the acid insoluble
      ash and water soluble ash values were 17.87 +/- 0.37 and 16.73 +/- 0.13,
      respectively. Preliminary phytochemistry of leaf showed that it contains tannins,
      flavonoids and saponins with no traces of alkaloids or anthraquinones. The water
      extract showed a dose related reduction in mean arterial blood pressure. At 10
      mg/kg, a reduction of 16.6 +/- 1.1 mmHg was observed, whereas at 30 mg/kg, a fall
      in mean arterial pressure of 38.3 +/- 0.6 mmHg was obtained. The hypotensive
      effect of the extract was significantly reduced with a prior administration of
      2.5 mg of either atropine or chlorpheniramine. This suggests the probable
      stimulation of muscarinic receptors in the heart or release of histamine into the
      circulatory system thereby causing the initial fall in blood pressure.

PMID- 18323250
TI  - Hypotensive effect of aqueous extract of the leaves of Phyllanthus amarus Schum
      and Thonn (Euphorbiaceae).
AB  - The plant of Phyllanthus amarus is used as diuretic and to lower blood pressure
      in traditional medicine practice. The effect of the aqueous extract of the leaves
      of Phyllanthus amarus on blood pressure was evaluated in normotensive male
      rabbits. Intravenously administered aqueous doses (5 mg to 80 mg/kg) of the
      extract to anaesthesized normotensive male rabbits produced a significant fall in
      mean diastolic, systolic and mean arterial pressures in a graded dose response
      manner. The dose of 5 mg/kg produced the least hypotensive effect, causing a fall
      in mean diastolic, systolic, and mean arterial pressure of 13.3 +/- 3.1, 19.7 +/-
      5.4, and 14.3 +/- 3.4 mmHg, respectively, while the dose of 80 mg/kg produced the
      greatest fall in mean diastolic, systolic, and mean arterial pressure of 49.7 +/-
      7.9, 45.5 +/- 9.5, and 48.00 +/- 6.5 mmHg, respectively. The extract had a
      greater blood pressure depressant effect on the diastolic blood pressure than on
      the systolic blood pressure. The highest dose of 80 mg/kg caused 62.5% fall in
      diastolic blood pressure, compared to the 33.2% fall in systolic blood pressure
      caused by the same dose. Atropine at the dose of 1 mg/kg blocked the hypotensive
      effect of the aqueous extract in a competitive manner. Promethazine at the dose
      of 1 mg/kg did not block the hypotensive effect of the aqueous extract, but
      potentiated the effect of the extract. After the administration of promethazine,
      the maximum tolerable dose of the extract was 40 mg/kg as compared to the initial
      dose of 80 mg/kg. The extract was found to decrease both the force and rate of
      myocardial contraction in a concentration dependent manner. The extract also dose
      dependently inhibited the intrinsic myogenic contraction of isolated rat portal
      vein. The results obtained show that the extract has blood pressure lowering
      effect which may be by the combined effects of myocardial depression, muscarinic
      receptor mediated vascular smooth muscle relaxation and by the calcium channel
      ion blockade in vascular smooth muscle.

PMID- 18323251
TI  - Multi-unit dosage formulations of theophylline for controlled release
      applications.
AB  - The study was carried out to investigate the drug release profiles of multi-unit
      dosage formulations of theophylline consisting of both the fast and slow release
      components in a unit dose. The fast release component consisted of conventional
      granules of theophylline formed by mixing the drug powder with starch mucilage
      (20% w/v) while the slow release component consisted of wax granulations of
      theophylline formed by triturating the drug powder with a melted Carnauba wax
      (drug:wax ratio, 4:1). The granules were either filled into capsules or
      tabletted. In the study design, the drug release characteristics of the
      individual fast or slow release particles were first determined separately and
      then mixed in various proportions for the purpose of optimizing the drug release
      profiles. The evaluating parameters were the prompt release in the first 1 h
      (mp), the maximum release (m infinity) and the time to attain it (t infinity).
      Total drug content in each capsule or tablet was 300 mg and two of such were used
      in dissolution studies. The release kinetics and hence the release mechanism was
      confirmed by measuring the linear regression coefficient (R2 values) of the
      release data. The release kinetics was generally most consistent with the Higuchi
      square root of time relationship (R2 = 0.95). indicating a diffusion-controlled
      mechanism. The mp (mg) and t infinity (h) values for capsules and tablets of the
      conventional granules were (420 mg, 3 h) and (348 mg, 5 h), respectively, while
      for the capsules and tablets of the wax granulations mp and t infinity values
      were (228 mg, 9 h) and (156 mg, 12 h), respectively, indicating that a
      combination of wax granulation and tableting markedly retarded drug release. In
      the multi-unit dose formulations where the conventional and wax granulations were
      mixed in the ratios 2:1, 1:1 and 1:2 (conventional: matrix), the m infinity and t
      infinity values for the capsules were (378 mg, 6 h), (326 mg, 6 h) and (272 mg, 7
      h), reSpectively. The corresponding values of m infinity and t infinity for the
      tablets were (240 mg, 9 h), (180 mg, 11 h) and (128 mg, 12 h) against the set
      target (200 mg, 12 h). The indication is that tableting rather than encapsulation
      can more effectively control drug release from the systems.

PMID- 18323252
TI  - Influence of sodium butyrate on hepatocellular carcinoma (hepG2) and glioblastoma
      (C6) cell lines in vitro.
AB  - Hepatocellular carcinoma and glioblastoma are both very aggressive forms of human
      neoplasms. The most effective treatment includes the combination of surgery,
      chemotherapy and radiation. Sodium butyrate (NaB) demonstrates a high efficiency
      and low toxicity. It inhibits proliferation and cell cycle of the cancer cells.
      The aim of this study was to investigate the effect of sodium butyrate on HepG2
      and C6 cell line viability. Hepatocellular cancer (HepG2) and glioblastoma cell
      line (C6) were cultured in DMEM/Ham's F12 medium with 10% FBS and antibiotics.
      Different NaB concentrations (0-10 mM) were tested. The control consisted of
      cells without tested substance. The incubation times were 24 and 48 h. Cell
      viability was studied using Trypan Blue exclusion test. Inhibitory influence of
      sodium butyrate on cell viability in both examined cell lines was confirmed.
      Strong correlation between NaB concentration and cell viability after 24 h was
      noticed (correlation coefficient was 0.94 and 0.98 for C6 and HepG2,
      respectively). IC50 values after 24 h were 8.44 mM and 6.17 mM for C6 and HepG2,
      respectively. The strongest effect was observed after 48 h of incubation with
      NaB. IC50 values were 3.44 mM and 1.47 mM for C6 and HepG2 (correlation
      coefficients after 48 h were 0.91 and 0.631 for C6 and HepG2, respectively). C6
      line was more resistant to NaB than HepG2. Both cell lines were sensitive to NaB
      treatment, which gives the promise that NaB can be used against broader spectrum
      of neoplasms in the future.

PMID- 18323253
TI  - Uric acid plasma level and urine pH in rats treated with ambroxol.
AB  - It was a chance discovery that ambroxol parenteral administration led to urinary
      bladder stone formation in rats. This study was undertaken to examine the serum
      uric acid levels and urine pH in rats after ambroxol parenteral treatment.
      Ambroxol influence on the uric acid level was measured in 5 rats (Rattus sp.)
      treated with 60 mg/kg (dissolved in injection water, sc, daily) during 2 weeks.
      Ambroxol influence on urine pH was examined on 45 rats divided into 3 groups.
      Rats from the 1st and 2nd group received 30 and 60 mg/kg/24h ambroxol,
      respectively. Urine was collected once daily and measured with strip kit. All
      values were presented as the means with standard deviations. The Student t test
      was used to compare the means, p < 0.05 was considered as significant. Dynamics
      of pH changes was measured in 4 rats treated with 60 mg/kg/24h of ambroxol.
      Controls received 1 mL of injection water sc. Serum uric acid level increased up
      to 8.7 +/- 1.0 mg/dL vs. 5.7 +/- 1.0 mg/dL in control (p < 0.002). In the 1st and
      2nd group urine pH increased up to 7.5 +/- 0.5 and 7.6 +/- 0.5 vs. 6.7 +/- 0.4 (p
      < 0.05). Ambroxol withdrawal resulted in sequential urine pH decrease. 11 days
      after interruption of ambroxol therapy pH reached the starting value. Urine pH
      changes and possible disturbances in uric acid metabolic pathway may influence on
      the stone formation in rats after ambroxol parenteral treatment. The influence of
      ambroxol on urinary tract GAG layer and the balance between xanthine and CaOx in
      the urine should be checked.

PMID- 18323254
TI  - Radiologic case study. Traumatic spinal epidural hematoma.

PMID- 18323255
TI  - Mentoring healers.

PMID- 18323256
TI  - The bull's eye view in slipped capital femoral epiphysis.

PMID- 18323257
TI  - Air bubble saline arthrosonography in imaging rotator cuff tears.

PMID- 18323258
TI  - Stabilization of pathologic long bone fractures with the Fixion expandable nail.

PMID- 18323259
TI  - Implication of food allergies and intolerances on medication administration.

PMID- 18323260
TI  - ACL tibial remnant, to save or not?

PMID- 18323261
TI  - Current concepts in synovial tissue of the knee joint.

PMID- 18323262
TI  - The OIIQ Youth Committee turns 10!

PMID- 18323263
TI  - [Family and aging: stakes and challenges for professional nurses and family
      caregivers].

PMID- 18323264
TI  - [Information system management and technology: the care milieus need a nursing
      resource].

PMID- 18323265
TI  - [The Interuniversity Research Group in Nursing Sciences of Montreal: a added
      value for the advancement of scientific and clinical knowledge].

PMID- 18323266
TI  - [Diane Nault, women and chronic obstructive lung disease. Interview by Marie
      Clark].

PMID- 18323267
TI  - [From head to toe, do you know how you dress?].

PMID- 18323268
TI  - [The therapeutic clown in the pediatric milieu].

PMID- 18323269
TI  - Rate of endometrial adenocarcinoma in women screened before and after
      implementation of the Bethesda 2001 reporting system.
AB  - OBJECTIVE: To assess the impact of the recommendation of the 2001 Bethesda System
      to report all benign-appearing endometrial cells seen in women aged > or = 40
      years on the frequency with which endometrial carcinomas are potentially detected
      as a consequence of Pap test reports that mention endometrial cells. STUDY
      DESIGN: We identified all women diagnosed with endometrial adenocarcinoma who
      also had a Pap test during the preceding 6 months. The search was performed for 3
      year periods before and after the date of implementation of Bethesda 2001.
      RESULTS: Benign endometrial cells were reported for 589 women in the 3 years
      before Bethesda 2001 and for 3,810 women in the 3 following years. The number of
      endometrial malignancies found on follow-up in these women decreased from 8 in
      the 3 years before Bethesda 2001 to only 4 subsequently. The frequency of
      reporting atypical or malignant glandular cells, as well as the likelihood of
      finding endometrial malignancy on follow-up, did not significantly change.
      CONCLUSION: Despite a 6.5-fold rise in the frequency of reporting benign
      endometrial cells after Bethesda 2001, the frequency of subsequent diagnosis of
      endometrial malignancies did not in-crease.

PMID- 18323270
TI  - Osteopenia and osteoporosis can be predicted from Pap test.
AB  - OBJECTIVE: To determine sensitivity and specificity of Pap tests for osteopenia
      and osteoporosis using bone mineral density (BMD) with dual x-ray absorptiometry
      (DXA) as the reference standard. STUDY DESIGN: DXA measurement was performed on
      136 routine Pap smears. Results of DXA measurement were expressed in T-scores,
      indicating degree of deviation compared to a young adult population of same age
      and gender. Smears were grouped into atrophic and mature cell patterns. Using a
      stereologic analysis, mean areas of squamous cells, their nuclei and their
      cytoplasm were estimated. RESULTS: There was significant positive correlation
      between cell area and T-score (p < 0.001), as well as between cytoplasm area and
      T-score (p < 0.001). There was no significant relationship between nucleus area
      and T-score (p > 0.05). Mean T-scores of patients with atrophic cells were
      significantly lower than mean T-scores of patients with mature cell patterns (p <
      0.001). The group including patients with atrophic or mature cells had a
      sensitivity of 61.4% and specificity of 86.4%, with positive predictive value of
      95.9% in detecting patients with osteopenia or osteoporosis. CONCLUSION: Women
      with atrophic smear pattern are susceptible to osteopenia or osteoporosis; many
      cases could be detected with routine Pap test without additional costs.

PMID- 18323271
TI  - Cytologic detection of esophageal squamous cell carcinoma and its precursor
      lesions using balloon samplers and liquid-based cytology in asymptomatic adults
      in Llinxian, China.
AB  - OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is associated with very high
      regional mortality rates in several countries. Our initial test of esophageal
      cytology screening devices found them not sensitive enough for an early detection
      program. The current study tested a newly designed "mechanical" balloon and a
      traditional Chinese inflatable balloon, followed by liquid-based cytology, to
      detect biopsy-proven squamous dysplasia and early cancer. STUDY DESIGN:
      Participants were randomized to a cytologic sampler, followed by endoscopy with
      iodine staining. For each patient, the cytologic diagnosis (test) was compared
      with the worst endoscopic biopsy diagnosis (truth). RESULTS: Seven hundred forty
      subjects completed both examinations. Approximately 30% showed atypical squamous
      cells of undetermined significance (ASCUS), and 10% showed squamous
      intraepithelial lesions. Seven hundred twenty-five subjects (98%) had
      satisfactory biopsies, and 32% had low grade dysplasia or worse disease. Defining
      > ASCUS, favor neoplastic, as a positive screening test, the
      sensitivities/specificities of the mechanical and inflatable balloons were
      39%/85% and 46%/84%, respectively, for detecting any squamous dysplasia or
      cancer. CONCLUSION: These esophageal cell samplers performed equivalently, but
      the accuracy was still too low for a primary screening test. These results
      highlight the need to develop new cytologic criteria or molecular markers that
      can better detect early squamous esophageal disease [corrected]

PMID- 18323272
TI  - Value of endoscopic retrograde cholangiopancreatography-guided brushings in
      preoperative assessment of pancreaticobiliary strictures: what's new?
AB  - Brush cytology plays a prominent role in confirming the presence of extrahepatic
      biliary tract malignancy. However, its value is limited by its relatively low and
      widely variable sensitivity values. Various factors seem to influence the
      accuracy of cytologic diagnosis and are attributed to sampling, technical and
      interpretation errors. Ancillary methods, such as immunocytochemistry, flow
      cytometry, image analysis, fluorescence in situ hybridization (FISH) and the
      newly discovered method of global analysis of gene expression are helpful in
      resolving cases with inconclusive cytology and are vigorously investigated for
      their value in assessing the expression of novel tumor markers for the diagnosis
      and prognosis of pancreatic and bile duct carcinomas. However, their routine use
      in clinical practice remains in doubt. To increase the sensitivity of brush
      cytology and strengthen its role in the preoperative assessment of patients with
      pancreaticobiliary malignancies, the following are of the utmost importance:
      improvement of current sampling and cytopreparation techniques, introduction of a
      uniform system for reporting epithelial abnormalities based on strict and clearly
      distinct morphologic criteria for each pathologic entity and incorporation of
      experience and knowledge derived from standard cytologic methods and novel
      diagnostic technologies in clinical practice without compromising the high
      specificity associated with brush cytology.

PMID- 18323273
TI  - Improved identification of malignant cells in serous effusions using a small,
      robust panel of antibodies on paraffin-embedded cell suspensions.
AB  - OBJECTIVE: To evaluate the expression of these markers individually and to find
      out which markers would be the most effective in a diagnostic panel to reliably
      discriminate these lesions. STUDY DESIGN: Sections from cell blocks of these
      fluids were stained with antibodies against calretinin, EMA, HMFG-2, BerEp4,
      B72.3 and CEA. A preliminary diagnosis was formulated based on cytomorphologic
      criteria. Subsequently, results of all 6 immunocytochemical stainings were
      evaluated, the most effective diagnostic pane of antibodies was proposed and
      staining results using this panel were compared to results obtained by solely
      cytomorphologic evaluation and to the ultimate diagnosis. RESULTS: Additional
      immunocytochemical staining with the proposed panel of calretinin, EMA, HMFG-2
      and CEA improved sensitivity for malignancy in general from 78% to 96% and
      specificity from 73% to 91%. Sensitivity for malignant mesothelioma increased
      from 45% to 91%, with an increase in specificity from 87% to 96%. Sensitivity for
      adenocarcinoma decreased slightly from 100% to 92%, but specificity increased
      from 86% to 100%. Overall, diagnostic accuracy increased from 76% to 94%.
      CONCLUSION: Immunocytochemical staining of standardized cell block reparations of
      serous fluid cells with a small panel of 4 antibodies significantly improves
      diagnostic results compared to cytomorphologic evaluation alone.

PMID- 18323274
TI  - Islet cell tumor of the pancreas: increasing diagnosis after instituting
      ultrasonography-guided fine needle aspiration.
AB  - OBJECTIVE: To review the clinical and cytomorphologic features of pancreatic
      islet cell tumors (ICT). STUDY DESIGN: Computer search identified patients with
      pancreatic ICT diagnosed by fine needle aspiration biopsy (FNAB) between January
      1995 and December 2003. Clinical, radiographic, and cytomorphologic findings were
      reviewed. RESULTS: Thirty-eight patients (19 men, 19 women; median age 60 years,
      range 30-82) with ICT were identified; 30 were diagnosed through endoscopic
      ultrasonography (EUS)-FNAB and 8 through computed tomography (CT)-guided FNAB.
      Smears of 37 specimens had adequate cellularity. Most were highly cellular with
      bloody backgrounds. No major differences were observed between specimens obtained
      by EUS-FNAB or CT-FNAB. Radiographically, 20 tumors measured 1-5 cm, 7 were > 5
      cm and 4 < 1 cm. Twenty-two patients underwent tumor resection. CONCLUSION: Newer
      radiography and biopsy techniques to detect and examine smaller pancreatic masses
      have increased the number of pancreatic ICT diagnoses at our institution. The
      distinctive cytomorphologic features of pancreatic ICT make it reliably
      diagnosable by FNAB.

PMID- 18323275
TI  - Open or closed nuclear membrane? A question to help distinguish malignant
      lymphoma from carcinoma and sarcoma.
AB  - OBJECTIVE: To describe a cytomorphologic criterion that may help improve
      diagnostic safety in morphologic differentiation of non-Hodgkin's lymphoma (NHL)
      from carcinoma or sarcoma and investigate the significance of this
      cytomorphologic phenomenon. STUDY DESIGN: Eighty-two smears of NHL, carcinoma and
      sarcoma smears were examined. Forty-five smears were from patients with carcinoma
      and 35 from patients with NHL. The remaining 2 smears were from patients with
      sarcoma. RESULTS: In 40 of 46 smears of carcinoma or sarcoma the nuclear membrane
      was assessed as "open" by the observer. In 6 smears the membrane was assessed as
      "closed. " In 30 of 35 smears with histologically confirmed NHL, the membrane was
      estimated as being closed. In the remaining 5 smears it was assessed as open. The
      sensitivity of evaluating the parameter as open or closed membrane was 87% and
      the specificity was 86%. The negative predictive value was 89%, and the positive
      predictive value was 83%. CONCLUSION: We suggest that the presence of an open or
      closed nuclear membrane may be helpful in differentiation of malignant lymphoma
      from carcinoma or sarcoma and may help improve diagnostic safety in daily
      practice.

PMID- 18323276
TI  - Histologic analysis and comparison of techniques in fine needle aspiration
      induced alterations in thyroid.
AB  - OBJECTIVE: To assess histologic alterations following fine needle aspiration
      (FNA) of the thyroid and differentiate these from ominous lesions, such as
      papillary carcinoma thyroid, as well as assess and compare the degree of tissue
      trauma from the techniques: needle only vs. needle with syringe, size of needle
      and number of aspirations. STUDY DESIGN: Thyroidectomy specimens of 100 cases
      with prior FNA biopsy were selected. The changes called "worrisome histologic
      alteration following fine needle aspiration of the thyroid" (WHAFFT) were
      studied. Number of FNAs, needle size and technique were tabulated for 73 of 100
      cases. RESULTS: Worrisome changes were confined to areas near the needle tract
      and hence could be differentiated from ominous lesions. Control cases did not
      show WHAFFT lesions. Non-aspiration FNA cytology (FNAC) technique results in
      fewer, less frequent WHAFFT changes. The increasing number of FNAs leads to
      statistically significant increase in infarction, necrosis and vascular changes.
      A gradation in the WHAFFT changes, directly proportional to the increasing
      diameter of the needle, was observed. CONCLUSION: The pathologist should be aware
      of WHAFFT to avoid misinterpretation. The technique of non-aspiration FNAC is
      significantly less traumatic. An increase in FNAs or size of needle results in
      more severe WHAFFT changes.

PMID- 18323277
TI  - Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the
      breast: review of 37 cases with histologic correlation.
AB  - OBJECTIVE: To analyze fine-needle aspiration cytology (FNAC) material from 37
      cases of breast glycogen-rich clear cell cancer (GRCC) and correlate
      cytomorphologic features with histologic appearance to determine characteristics
      of GRCC on FNAC. STUDY DESIGN: We reviewed cytologic features of 37 cases of
      breast GRCC from the archives of Ege University Hospital diagnosed between 1994
      and 2006. RESULTS: Thirty-seven patients with available aspirate and confirmed
      GRCC were identified. The female patients ranged from 32 to 81 years (mean 52
      years). The initial cytologic diagnoses were adenocarcinoma for 27 and atypical
      or suspicious for cancer for 10. The cytologic picture was characterized by
      hypercellular tumor cells in loosely cohesive syncytial groups and some single
      cells. Most tumor cells had abundant, finely granular eosinophilic cytoplasm or
      foamy to clear cytoplasm with well-defined cytoplasmic membranes and moderate to
      marked nuclear pleomorphism with prominent nucleoli. Histologic examination
      confirmed all cases to be pure GRCC. CONCLUSION: Breast GRCC is a rare, distinct
      category with cytologic features that overlap considerably with those of other
      carcinomas. Awareness of variability in cytomorphologic appearance of GRCC and
      routine assessment for glycogen facilitate accurate diagnosis of these lesions by
      FNAC and enable prompt treatment of these poor-prognosis breast cancers.

PMID- 18323278
TI  - Cytologic differentiation of struma ovarii from other ovarian neoplasms.
AB  - OBJECTIVE: To present the cytologic findings of struma ovarii and value of
      cytology and immunocytochemistry (ICC) using thyroglobulin (TGB) and thyroid
      transcription factor-1 (TTF-1) in evaluation of this unusual ovarian neoplasm,
      together with the diagnostic pitfalls. STUDY DESIGN: Intraoperative cytologic
      findings of 7 patients with struma ovarii are reviewed. Cytologic material of
      both cystic and solid components was collected intraoperatively. ICC staining was
      done, and cell block preparation performed on selected cases. RESULTS: The cases
      were divided in to 3 groups: group 1--diagnosis of struma ovarii was made by
      cytology and confirmed by ICC (1 case); group 2--diagnosis was suggestive on
      cytology or cell block and confirmed by ICC staining (4 cases); group 3--on
      cytologic diagnosis indistinguishable from other cystic ovarian neoplasms (2
      cases). Cytologic findings were typically colloid with mosaic pattern, follicles,
      follicular cells only, sheets of follicular cells, both colloid and follicular
      cells, proteinaceous background or degenerated epithelial cells indistinguishable
      from other cystic ovarian neoplasms. CONCLUSION: Cytologic findings of struma
      ovarii are distinct enough to be suggested intraoperatively, and ICC for TGB or
      TTF-1 is a valuable tool for preoperative fine needle aspiration biopsy and
      intraoperative diagnosis of this benign ovarian neoplasm.

PMID- 18323279
TI  - Comparison of cytohistologic techniques in diagnosis of gastroesophageal
      malignancy.
AB  - OBJECTIVE: To evaluate the diagnostic performance of various endoscopic cytologic
      techniques, namely, brushing cytology, touch smear cytology and crush cytology,
      and comparison with concurrent biopsy results in diagnosis of gastroesophageal
      malignancy. STUDY DESIGN: This prospective study was conducted on 100 patients,
      with 78 clinically suspected cases of esophageal malignancy and 22 cases of
      gastric malignancy. RESULTS: The diagnostic accuracy of touch smear in esophageal
      malignancy was significantly higher (94.12%) than brushing and crush smears
      (89.71% each), and endoscopic biopsy had the diagnostic accuracy of 88.24%. The
      diagnostic accuracy of combined brushing and biopsy was 100%; it was 97.06% for
      touch smears combined with biopsy. In comparison, the diagnostic accuracy in
      gastric malignancy was 75% for brushing alone, which was significantly lower than
      touch smear (87.5%) and endoscopic biopsy (87.5%). The diagnostic yield for crush
      smear was 81.25%. A combination of touch smears and biopsy had a diagnostic yield
      of 100%; it was 93.75% for combined brushings and biopsy. CONCLUSION: A
      combination of cytohistologic techniques resulted in a statistically significant
      increase in the diagnostic yield of gastroesophageal malignancies and thus
      cytologic techniques may act as adjunct to biopsy histology to increase the
      diagnostic efficiency.

PMID- 18323280
TI  - Anaplastic large cell lymphoma in a human immunodeficiency virus-positive patient
      with cytologic findings in bladder wash: a case report.
AB  - BACKGROUND: Anaplastic large cell lymphoma (ALCL) (Ki-1/CD-30 positive) is an
      uncommon lymphoproliferative disorder that may be of T cell or null cell type.
      ALCL has been reported in fine needle aspirations of lymph nodes and pleural or
      peritoneal fluid cytology. In human immunodeficiency virus (HIV)-positive
      patients, ALCL appears to be more common and run a more aggressive course. CASE:
      A 39-year-old black man, seropositive for HIV, presented with acute renal failure
      secondary to bilateral ureteral obstruction by a pelvic mass involving the
      urinary bladder. Bladder wash cytology and subsequent biopsy of the mass were
      diagnostic of ALCL. The ALCL was CD30+ and null cell type, with negative CD2,
      CD3, CD4, CD5, CD7, CD8, CD20, CD45, CD79a, ALK-1, granzyme B, cytokeratin
      (AE1/AE3), placental alkaline phosphatase (PLAP) and S-100. The patient expired 9
      months after the diagnosis, despite aggressive therapy. CONCLUSION: This is a
      rare occurrence of ALCL (CD 30 positive, null cell type) in the urinary bladder
      in an HIV+ patient. Presumptive diagnosis was made by bladder wash cytology and
      subsequently confirmed by biopsy. Urinary cytologic examination is a useful
      diagnostic tool. In HIV+/immunosuppressed patients with urinary symptoms and an
      obstructive mass, ALCL should be considered in the differential diagnosis.

PMID- 18323281
TI  - Cytologic diagnosis of ocular melanocytoma: a case report.
AB  - BACKGROUND: Pigmented lesions of the eye represent a challenging field from both
      clinical and pathologic approaches. The importance of a correct diagnosis in this
      case is enhanced by the delicate structures involved and their difficult
      accessibility. CASE: We report a case of a 51-year-old man with acute vision loss
      and the feeling of a foreign body in the left eye diagnosed with vitreous
      hemorrhage. A small, pigmented lesion in the proximity of optic nerve head was
      detected. After a 9-year follow-up, a definitive diagnosis of melanocytoma was
      achieved in vitrectomy cytology. Smears showed a population of plump, cohesive
      melanocytes and elongated cells with cytoplasmic melanin and uniform rounded
      nuclei. No change in the lesion has occurred 3 years after vitrectomy.
      CONCLUSION: Fine needle aspiration proved to be helpful and reliable for the
      correct diagnosis of melanocytoma, which does not require additional treatment.

PMID- 18323282
TI  - Cytology of cystic nephroma: a case report.
AB  - BACKGROUND: Cystic nephroma is a rare benign multiloculated cystic renal neoplasm
      that is often confused with multicystic renal cell carcinoma radiographically and
      cytologically. CASE: A 58-year-old woman was incidentally found to have a
      multiloculated cystic right renal lesion. Cytologic examination of the fluid
      aspirated from the lesion was reported as highly suspicious for renal cell
      carcinoma, but a right nephrectomy revealed a cystic nephroma. CONCLUSION: Cystic
      nephroma fluid is characterized by the presence of sparse epithelial cells with
      moderate nuclear atypia. Conversely, the fluid of multicystic renal cell
      carcinoma is moderately cellular with no or mild nuclear atypia.

PMID- 18323283
TI  - Fine needle aspiration of urethral recurrence of urothelial carcinoma after
      radical cystectomy presenting as a perineal mass: a case report.
AB  - BACKGROUND: Recurrence of urothelial (transitional cell) carcinoma in the urethra
      after cystectomy for invasive urothelial carcinoma is relatively uncommon. It is
      also uncommon for the recurring urethral tumor to present as a painful perineal
      mass. Fine needle aspiration (FNA) can be used to evaluate such perineal lesions
      and confirm tumor recurrence. CASE: A 5-cm-diameter mass was found in the
      perineum of a 63-year-old man 1 year after radical cystoprostatectomy for
      invasive urothelial carcinoma of the urinary bladder. The mass was detected on
      pelvic computed tomographic scanning. FNA cytology showed numerous urothelial
      carcinoma cells of high grade displaying squamous cell differentiation mimicking
      the histopathologic findings of the primary tumor found on cystectomy. Diagnosis
      of recurrent urothelial carcinoma was rendered. The FNA in this case spared the
      patient an open biopsy. CONCLUSION: Mass lesions arising in the perineum of
      patients who underwent cystectomy for urothelial carcinoma should raise the
      suspicion of urothelial carcinoma recurrence. Evaluation of perineal masses for
      recurrence of urothelial carcinoma can be made on FNA without the need for open
      biopsy.

PMID- 18323284
TI  - Fine needle aspiration cytology of mammary carcinoma with choriocarcinomatous
      features: a report of 2 cases.
AB  - BACKGROUND: Neoplasms of the breast containing multinucleated giant cells (MGCs)
      include both benign and malignant entities, such as benign soft tissue giant cell
      tumors, atypical fibrous histiocytoma, sarcomas, metaplastic carcinomas and the
      uncommon carcinomas containing osteoclast-like giant cells (OGC). Breast
      carcinoma with choriocarcinomatous features (BCCF) is a distinct variant of
      breast cancer. CASES: We report the cytologic features, pathologic findings and
      immunohistochemical profile in 2 cases of this unusual variant of breast
      carcinoma. Two women aged 53 and 50 years women presented with a history of left
      and right breast lump but no local lymphadenopathy, respectively. Fine needle
      aspiration cytology (FNAC) of both cases revealed abundant MGC with highly
      pleomorphic tumor cells in the hemorrhagic necrotic background. Both of the cases
      were histopathologically diagnosed as BCCF. CONCLUSION: Choriocarcinomatous
      differentiation with multinucleated syncytiotrophoblast-like giant cells is
      extremely rare in breast tumors. Although rare, FNAC of breast cancer with
      pleomorphic MGC requires careful search for differential diagnosis; breast
      carcinoma with giant cell features (choriocarcinomatous features, OGC features)
      must be differentiated from metastatic tumors and other breast lesions containing
      giant cells.

PMID- 18323285
TI  - Occult medullary carcinoma of thyroid with lymph node metastases: a case report.
AB  - BACKGROUND: Occult thyroid malignancies presenting with secondary neck masses as
      the first clinical manifestation is well known. Although rare, medullary
      carcinoma serves a potential source for lymph node metastases. The characteristic
      cytomorphology of medullary thyroid carcinoma (MTC) should clinch the diagnosis.
      Further, fine needle aspiration cytology (FNAC) of the ultrasonography-detected
      occult nodules in thyroid serves as a useful preoperative diagnostic tool. CASE:
      A 22-year-old man presented with left-sided neck masses of 1 year duration. FNAC
      smears of the neck masses revealed cytomorphology characteristic of MTC.
      Ultrasonography of the thyroid led to ruling out the presence of an occult nodule
      and detected an 8-mm nodule in the left thyroid lobe. Ultrasound-guided FNAC of
      the nodule showed features similar to those with FNAC of the neck masses.
      Surgical resection of thyroid and neck masses further confirmed the diagnosis of
      a primary occult MTC with lymph node metastases. CONCLUSION: FNAC smears of lymph
      node masses showing the distinct cytomorphology of MTC should prompt suspicion
      for occult primary in thyroid. Ultrasound-guided FNAC of these occult nodules, if
      detected, further serves a diagnostic tool for accurate preoperative diagnosis
      when metastasis presents as the first clinical manifestation of an occult
      primary.

PMID- 18323286
TI  - Fine needle aspiration cytology of epithelioid angiosarcoma: a case report.
AB  - BACKGROUND: Malignant vascular tumors are rare. Few studies have described
      cytomorphologic features of hemangioendothelioma and angiosarcoma on fine needle
      aspiration cytology (FNAC). Malignant vascular tumor with epithelioid morphology
      can create diagnostic difficulty, as the cytology may simulate that in other
      nonvascular malignant tumors. We describe epithelioid angiosarcoma, diagnosed on
      FNAC, in which a differential diagnosis of histiocytosis and inflammatory
      granulation tissue was considered. CASE: A 20-year-old man presented with
      forehead and scalp swellings. The forehead lesion was radiologiocally associated
      with a lytic lesion in the bone. FNA resulted in high cellular yield, and smears
      revealed prominent vascular pattern with endothelial cell atypia and
      histiocytoid/epithelioid neoplastic cells, occasional mitotic figures and a few
      cells displaying nuclear grooving. Smear background showed a significant number
      of neutrophils. Epithelioid hemangioendothelioma/angiosarcoma, histiocytosis and
      inflammatory granulation tissue were considered. A cytologic diagnosis of
      epithelioid angiosarcoma/epithelioid hemangioendothelioma was suggested and
      confirmed on histopathologic and immunohistochemical examination. CONCLUSION:
      Cellular aspirates from malignant epithelioid endothelial tumors involving bone
      may be cytologically mistaken for histiocytosis and, rarely, inflammatory
      granulation tissue. However, prominent vascular pattern with striking endothelial
      cell atypia, presence of mitotic figures and careful search for presence of
      endothelial differentiation are helpful in accurate cytologic diagnosis.

PMID- 18323287
TI  - Comments on "Scientific issues related to the cytology proficiency testing
      regulations".

PMID- 18323288
TI  - Cytologic findings of rhabdoid meningioma in cerebrospinal fluid.

PMID- 18323289
TI  - Cytologic, histologic and immunocytochemical features in fine needle aspiration
      of paraganglioma-like variant of medullary carcinoma.

PMID- 18323291
TI  - Evidence-based public health benefits communities.

PMID- 18323290
TI  - Our vision for U.S. Health Care: we can get there from here.

PMID- 18323292
TI  - Evaluating community benefit programs: asking the right questions.

PMID- 18323293
TI  - What is stable patrimony?

PMID- 18323294
TI  - The mission leader and the 'A position'.

PMID- 18323295
TI  - Formation path in the workplace: how does it work? This traditional process
      focuses on personal and spiritual growth.

PMID- 18323296
TI  - Continuing the mission. How do health care leaders keep Catholic identity alive
      in today's world?

PMID- 18323297
TI  - Forming leaders in the business of health care. Trinity Health uses a disciplined
      process rooted in Christian spirituality and theology.

PMID- 18323298
TI  - Leadership formation: a call to action. How can the next generation of leaders
      carry Jesus' healing ministry in Catholic health care?

PMID- 18323299
TI  - The importance of leadership formation. Collaborative opportunities exist between
      Catholic health care and Catholic Universities.

PMID- 18323300
TI  - Formation of lay sponsors. Seven leaders reveal their thoughts on the topic.

PMID- 18323301
TI  - Cooperating with philanthropic organizations. How to assess the moral
      permissibility of a Catholic health care organization's involvement.

PMID- 18323302
TI  - No need for embryos? Recent discoveries dramatically alter the stem-cell debate.

PMID- 18323303
TI  - Defending the donor's decision. An analysis of the ethical issues related to
      first-person declarations of organ donation.

PMID- 18323304
TI  - Lessons in leadership.

PMID- 18323305
TI  - PeaceHealth employees benefit from El Salvador health missions.

PMID- 18323306
TI  - Arizona Medical Center shows how to be a 'healing hospital'. Technology, culture
      shift, and quiet nights lead transformation.

PMID- 18323307
TI  - The state of South Dakota's child: 2007.
AB  - The year 2006 brought a 4 percent increase in births to the state that was almost
      entirely attributed to an increase in white newborns. The rate of low birth
      weight births decreased for newborns weighing less than 1,500 grams but increased
      for those weighing 1,500 to 2,500 grams. The state's rate of low birth weight,
      however, remained less than the persistently climbing U.S. rate. The incidence of
      prenatal care beginning in the last trimester of pregnancy, or no prenatal care,
      increased and is of concern in light of recent findings from a South Dakota
      report that shows how failure to receive this care is related to infant
      mortality. The state's overall infant mortality rate decreased from its 2005
      rate. This decrease is attributable to a decrease in the rate of neonatal deaths
      for the state's white population. Rates of neonatal death increased for the
      minority population and post-neonatal mortality increased for both the white and
      minority population. How these findings are related to social and economic
      disparities is discussed.

PMID- 18323308
TI  - Premature ovarian failure: a phenotypic expression of fragile X premutation.
AB  - Fragile X syndrome is the most common cause of mental retardation in the male.
      Historically, fragile X premutation was considered to be phenotypically silent.
      In recent reports the premutation has been associated with premature ovarian
      failure and fragile X-associated tremor/ataxia syndrome. This case describes a 24
      year-old woman who presented with irregular menstrual cycles secondary to
      premature ovarian failure. Subsequent genetic analysis confirmed that she has a
      premutation for fragile X with 70 CGG trinucleotide repeats.

PMID- 18323309
TI  - A new option for the treatment of fibromyalgia.

PMID- 18323310
TI  - Compliance.

PMID- 18323311
TI  - Resistant organisms.

PMID- 18323312
TI  - Medicare Physician Quality Reporting Initiative (PQRI).

PMID- 18323313
TI  - Experience with a patient having multiple gunshot wounds in combat.

PMID- 18323314
TI  - Development of a position statement: the nurse anesthesia program administrator.

PMID- 18323315
TI  - Body piercing and airway management: photo guide to tongue jewelry removal
      techniques.
AB  - Body modification has been practiced in cultures around the world for thousands
      of years. The ramifications of body piercing on anesthesia practice and airway
      management have become more evident in recent years. This article reviews the
      techniques for removal of tongue jewelry and options for maintaining oral
      piercing patency. To remove or not to remove...that is the question. In the
      emergency medicine and anesthesia literature, there are arguments both for and
      against the routine removal of oral jewelry for intubation. Some practitioners
      feel that if people can eat, drink, talk, and sleep with the jewelry in place,
      they probably can be intubated safely without removing it. Most case reports
      present the opinion that tongue jewelry should be removed before oral intubation
      to minimize jewelry aspiration, bleeding, and medical-legal risks to the
      anesthetist. This article's focus is to illustrate suggested tongue jewelry
      removal techniques for awake and unconscious patients from the health
      practitioner's and body piercer's perspectives.

PMID- 18323316
TI  - Asystole during laryngoscopy of a patient with pleural and pericardial effusions:
      a case report.
AB  - A 53-year-old woman presented to the operating room for surgical correction of
      pericardial and pleural effusions. Her history included stage IV breast cancer,
      well-controlled hypertension, and diverticulitis. Although her baseline blood
      pressure, heart rate, and respirations were normal, she was short of breath with
      diminished breath sounds on the left side of the lungs and required oxygen, 2
      L/min via nasal cannula. The nurse anesthesia student, under the direction of the
      Certified Registered Nurse Anesthetist (CRNA) and anesthesiologist, induced
      general anesthesia with etomidate, fentanyl, lidocaine, and succinylcholine.
      During placement of a double-lumen endotracheal tube, the patient became
      asystolic. The nurse anesthesia student immediately withdrew the laryngoscope,
      and the patient returned to normal sinus rhythm. A second attempt at laryngoscopy
      produced asystole as well. Again, the laryngoscope was withdrawn, and the patient
      returned to normal sinus rhythm. After resuming ventilation with 100% oxygen and
      administering atropine, 0.4 mg, the next intubation was successful, producing no
      untoward effects. Reintubation at the end of the case with a single lumen
      endotracheal tube was uneventful. The patient was transported to the intensive
      care unit and mechanically ventilated overnight. The next morning, she was
      extubated with no further anesthetic complications.

PMID- 18323317
TI  - CRNA performance using a handheld, computerized, decision-making aid during
      critical events in a simulated environment: a methodologic inquiry.
AB  - Directives to improve patient outcomes and enhance safety within the healthcare
      system have led to development of technologies to assist practitioners in a
      variety of activities. The purpose of this study was to explore and evaluate a
      method for examining the effect of computer-assisted decision making (CADM) using
      a handheld device on the accuracy (ie, correct diagnosis and treatment) and speed
      of problem solving by Certified Registered Nurse Anesthetists (CRNAs) during
      simulated critical patient-care events. A randomized crossover design with
      matched-pair sampling was used. In a high-fidelity human simulation environment,
      4 CRNAs participated in 2 plausible critical anesthesia case scenarios. CRNA
      performance with and without CADM technology, environmental authenticity, and
      reliability and validity of data collection tools and simulated case scenarios
      were evaluated. Time to correct diagnosis and treatment varied by scenario,
      taking less time with CADM for one but more with CADM for the other, likely due
      to differences in pace, intensity, and conduct of the 2 scenarios. We believe
      this study supports further exploration and application of CADM in complex
      patient scenarios involving anesthesia practitioners. Affirmation of
      environmental authenticity also validates the high-fidelity human simulation
      environment as an appropriate setting to conduct research in this area.

PMID- 18323318
TI  - Epidural conduction device fractures and complications of retained fragments.
AB  - During the past 3 years, the US Food and Drug Administration (FDA) has received a
      growing number of adverse event reports on the breakage or fracturing and
      retention of anesthetic conduction device tips with associated complications.
      Serious injuries and other problems such as spinal stenosis, nerve root
      compression, and subcutaneous effusion can result. Several case reports
      demonstrate how the problems occur; some illustrate the severity of the problem.
      All cases are from adverse event reports in the FDA Center for Devices and
      Radiological Health (CDRH) Manufacturer and User Facility Device Experience
      database. Frequently, in the interest of not causing patient harm, a device
      fragment might not be removed as long as the patient is not neurologically
      compromised or at risk for infection or there is little potential for migration
      of the fragmented piece. On many occasions, the fragments remain in patients
      without their knowledge. The FDA wants to raise awareness of the problem and its
      potential impact in creating complications, encourage the practice of informing
      patients of the fragmented device, and promote reporting of such incidents to
      CDRH via the MedWatch reporting system. Based on a search of the current
      literature, recommendations for prevention are suggested.

PMID- 18323319
TI  - Heart block and prolonged Q-Tc interval following muscle relaxant reversal: a
      case report.
AB  - Heart block and Q-Tc interval prolongation have been reported with several agents
      used in anesthesia, and the US Food and Drug Administration mandates evaluation
      of the Q-T interval with new drugs. Drug-induced Q-T interval prolongation may
      precipitate life-threatening arrhythmias, is considered a precursor for torsades
      de pointes, and may predict cardiovascular complications. In the patient
      described in this article, heart block occurred and the Q-Tc interval became
      prolonged after muscle relaxant reversal with neostigmine; both were considered
      to be related to the combination of agents used in the case, as well as to other
      predisposing factors such as morbid obesity. The agents used that affected
      cardiac conduction were neostigmine, desflurane, droperidol, dolasetron, and
      dexmedetomidine. Although the heart block was resolved after 2 doses of atropine,
      prolonged P-R and Q-Tc intervals persisted into the immediate postoperative
      period but returned to baseline within 4 hours. Clinical implications of this
      report include increasing awareness of the multitude of factors affecting Q-T
      interval prolongation during anesthesia.

PMID- 18323320
TI  - Investigation of the anxiolytic effects of linalool, a lavender extract, in the
      male Sprague-Dawley rat.
AB  - The purpose of our study was to investigate the anxiolytic effects of linalool
      and its potential interaction with the GABAA receptor in Sprague-Dawley rats.
      Lavender has been used traditionally as an herbal remedy in the treatment of many
      medical conditions, including anxiety. Linalool is a major component of the
      essential oil of lavender. Forty-four rats were divided into 4 groups: control,
      linalool, midazolam (positive control), and flumazenil and linalool. The
      behavioral and the neurohormonal/physiological components of anxiety were
      evaluated. The behavioral component was examined by using the elevated plus maze
      (open arm time/total time) and the neurohormonal/physiological component by
      measuring serum catecholamine and corticosterone levels. Data analysis was
      performed using a 2-tailed Multivariate Analysis of Variance and Sheffe post-hoc
      test. Our data suggest that linalool does not produce anxiolysis by modulation of
      the GABAA receptor; however, linalool may modulate motor movements and
      locomotion.

PMID- 18323321
TI  - Suspected amniotic fluid embolism following amniotomy: a case report.
AB  - Amniotic fluid embolism (AFE), also referred to as anaphylactoid syndrome of
      pregnancy, is a rare obstetric emergency that may manifest itself at any time
      during pregnancy. AFE is believed to occur when the constituents of amniotic
      fluid enter the maternal circulation, leading to varying degrees of multiorgan
      compromise. AFE was first described in 1926, gaining widespread recognition in
      1941. This article describes the pathogenesis of AFE, including theories of its
      immunological mediation available in the literature. The most current diagnostic
      and treatment modalities are discussed, including several novel therapies. A case
      report of a 40-year-old parturient who suffered probable AFE following amniotomy,
      with the development of cardiopulmonary compromise, neurologic involvement, fetal
      distress, and coagulopathy, is outlined. The patient survived emergency cesarean
      delivery and hysterectomy with no residual physiologic deficits.

PMID- 18323322
TI  - Oxygen: the two-faced elixir of life.
AB  - Take a moment and consider our planet without oxygen. Imagine the earth some 2.5
      billion years ago when oxygen first appeared as a waste product of early
      anaerobes. Oxygen, as we know it today, is essential for life. Abundant and
      relatively inexpensive to manufacture, oxygen has widespread use in industry and
      healthcare. Anesthesia providers routinely administer oxygen in concentrations
      exceeding that in ambient air to ensure clinical safety and to offset the
      predictable sequelae associated with patient, drug-related, and procedural
      factors. Understanding the history of this unique element is critical in
      evaluating the often contentious body of contemporary research that has
      illuminated its efficacy (as elixir) and its attendant complications (its "two
      faced" nature). Of particular interest is its role in free radical formation as
      etiogenic in developing complications. Oxygen is a mainstay in the perioperative
      management of patients, but its administration should be guided by thoughtful and
      rational goal-directed outcomes to maximize efficacy and minimize complications
      associated with its use.

PMID- 18323323
TI  - [Cochlear implants in children with mental disabilities].
AB  - INTRODUCTION: Nowadays, profoundly deaf children with associated psychotic
      disorders can sometimes benefit from a cochlear implant program. These fragile
      children who have a specific development need a reinforced observation and follow
      up, and active parental collaboration. METHODS: From a series of 8 children with
      psychotic disorders implanted between 1999 and 2006, we present 4 representative
      cases of our practise, which have at least 3 years post implant. RESULTS: The
      questions that should occur about the conditions of the cochlear implantation are
      discussed in the light of the results of our observations. No children
      deteriorated them selves. All of them use their cochlear implant continuously.
      CONCLUSION: Cochlear implant is a tool in a global approach towards mobilization
      of communication resources in such children.

PMID- 18323324
TI  - [Usher type I syndrome in children: genotype/phenotype correlation and cochlear
      implant benefits].
AB  - OBJECTIVE: To assess the benefit of cochlear implant in children presenting an
      Usher type 1 syndrome (speech understanding, speech production intelligibility,
      academic performance) and to search any correlation between the phenotype and the
      genotype in this population. MATERIALS AND METHODS: Retrospective case series
      analysis about 13 implanted Usher type I children. Cochlear implantation was
      performed from 1995 to 2005. Our population was divided in three groups: group 1
      (implantation between 1 and 3 years of age); group 2 (implantation between 4 and
      7 years of age) and group 3 (implantation between 14 and 17 years of age).
      Postoperative speech perception, speech production intelligibility and education
      settings were evaluated. RESULTS: Molecular genetic analysis was performed in 11
      patients and pathogenic mutations were identified in all cases: (mutation in
      myosin 7A gene in 5 cases; mutation in cadherin 23 gene in 6 cases). Four new
      mutations 2 in the MYO7A gene and 2 in the CDH23 gene never reported before were
      found. Walking delay and hearing level were not statistically correlated with the
      genotype abnormalities found. The speech discrimination skills, the speech
      production intelligibility and the academic performance were better in the group
      1 children than the group 2 children after cochlear implantation. All the
      children of group 1 but one were in mainstreaming education. Specific language
      impairment was identified in two children of group 1. The group 3 children could
      not achieve open-set perceptive tasks after implantation--only closed-set word
      test can be done and their speech production remained unintelligible after
      cochlear implantation. CONCLUSION: Molecular analysis of Usher type I syndrome
      can ascertain the diagnosis in spite of the genetic heterogeneity. In this study,
      clinical symptoms weren't correlated with genotypic mutations. Speech
      discrimination skills, speech production quality, and academic performance were
      correlated with the age at implant.

PMID- 18323325
TI  - [TRT: results after one year treatment].
AB  - INTRODUCTION: Tinnitus Retraining Therapy (TRT) (which aims to induce changes in
      the mechanisms responsible for transferring signals from the auditory system to
      the limbic and autonomic systems) is a method for treating Tinnitus and decreased
      sound tolerance. An individualised explanation of Jastreboff's neurophysiological
      model allows greater insight and motivation on the part of the patient. Previous
      studies have demonstrated that daytime TRT is effective. As sleep forms a
      significant component of the distress associated with Tinnitus however, we
      hypothesised that night-time TRT could represent a useful tool in the treatment
      of this disabling condition. MATERIAL AND METHODS: 46 patients were studied (30
      male, 16 female). Patients were selected from an ENT outpatient clinic. Patients
      with significant psychological disability were excluded. Patients were reviewed
      twice by their doctor and 5 times by a therapist over 12 months. Treatment
      consisted of 8 hours nighttime white noise stimulation, at progressively
      increasing intensity. Although several objective assessments of response were
      undertaken, patients' subjective testimonies were considered a more accurate
      signal of success. RESULTS: In total, 80% of patients had a satisfactory response
      after 1 year of treatment. 20% had no response. Patients were subcategorised
      according to Jastreboff's categories as follows: 1. Tinnitus (n = 6), 100%
      improved; 2. Tinnitus with hearing loss (n = 16); 62% improved; 3. Hyperacusis
      (with or without Tinnitus) (n = 16), 88.5% improved; 4. Hyperacusis (with or
      without Tinnitus, exacerbated by noise) (n = 8), 75% improved. CONCLUSION:
      Tinnitus is a symptom rather than an illness, and TRT gives patients greater
      control, allowing re-integration of normal perception. Night-time TRT is an
      effective treatment for Tinnitus and decreased sound tolerance. It has the
      potential advantage over day-time TRT of rapidly improving sleep and decreasing
      use of sedative hypnotics, a secondary effect noted in the personal testimonies
      of our cohort of patients. Further studies are needed to confirm this advantage,
      in view of the significant risks associated with long-term use of
      benzodiazepines. When investigating therapies for Tinnitus, it is necessary to
      measure success in terms of quality of life, as it is to this that the patient
      attaches the most importance.

PMID- 18323326
TI  - [Supra and infra hyoid midline cervical cysts or hyoglossal abnormalies: a propos
      of 45 cases].
AB  - OBJECTIVES: To specify the embryologic origin of the sus and sub hyoidal midline
      cervical cysts after studying a series of 45 patients. MATERIALS AND METHODS: 45
      files were analyzed retrospectively between 1983 and 2004. RESULTS: The
      population concerns 21 women and 24 men with ages going from 3 to 71 years (8
      children of less than 10 years). The location of the lesions is supra-hyoidal
      (12), sub-hyoidal (27), pre-hyoidal (2), basi-lingual (4), a cyst was a
      fortuitous discovery at the time of a laryngeal surgery. All these patients were
      operated by external way with resection of the hyoid bone in 40 cases. The
      histological examination made it possible to differenciate 18 cysts associated
      with thyroid vesicules, 24 granulomatous cysts, 1 mucoid cyst, 1 epidermidal cyst
      and 1 ectopic thyroid. Four observations are more precisely detailed. CONCLUSION:
      In spite of the strong proportion of cysts of the thyroglossal tract there is
      different types of cysts evoking a median dysraphy. Rather than speaking about
      thyroglossal anomalies, the authors propose to call them hyo-glossal anomalies
      because these lesions are always involving the hyoid bone. The situation of
      thyroid gland must always be located before surgery, clinically, by echography or
      scintigraphy. The surgical technique must remove the hyoid bone in monobloc while
      going up until the contact of the base of the tongue.

PMID- 18323327
TI  - [Outcome of surgical and adjuvant radiotherapy treatment of T3-T4 squamous cell
      carcinoma of the floor of the mouth: evaluation of oncological control and
      treatment related morbidity].
AB  - OBJECTIVE: The aims of this study were to evaluate the therapeutic outcome and
      morbidity associated with management of squamous cell carcinoma (SCC) T3-T4 of
      the floor of the mouth. PATIENTS AND METHODS: This was a retrospective study
      (1993 and 2005). Inclusion criteria were: 1) Presence of a locally advanced (T3
      T4) lesion of the floor of the mouth; 2) Pathological confirmation of SCC; 3) No
      previous treatment of the floor of the mouth; 4) Absence of any synchronous
      lesions at the primary endoscopic work-up; 5) Absence of distant metastasis
      outside the aero-digestive tract; 6) Karnofsky performance index > 70. All
      patients were treated by surgery and adjuvant radiotherapy. The statistical
      analysis was conducted using the stat-view software; categorical variables were
      compared using the Fisher's exact test; analysis of recurrence-free survival rate
      was done following the Kaplan-Meier method, and the log-rank test was used for
      the comparison of survival graphs. RESULTS: Fourty-seven patients were included
      in this study (42 men), of a mean age of 53.3 years. The majority of patients
      (93.6%) presented with a stage IVa tumour and no clinical evidence of cervical
      lymphadenopathy in 60% of cases. All patients underwent bilateral neck dissection
      adapted to the cervical lymph node status. Forty-one (87%) patients underwent
      partial mandibulectomy with fibula free-flap reconstruction in 32 cases (78%).
      Early local complication rate was of 32%. The mean duration of hospitalization
      was 34 days. Late local complication rate was of 17%. The immediate post
      operative death rate was 2%. The rate of survival and recurrence free survival
      was of 47.5% and 47% respectively. The 3 survival-influencing factors were age (p
      = 0.02), margins of surgical resection (p = 0.002), and histologic cervical lymph
      node status (p = 0.03). CONCLUSION: T3-T4 tumours of the floor of the mouth are
      managed by surgical resection and adjuvant radiotherapy. There is a high rate of
      treatment-associated complications. The prognosis of locally advanced tumours of
      the floor of the mouth remains humble.

PMID- 18323328
TI  - Voice rehabilitation after total laryngectomy using the Newvox voice prosthesis.
AB  - OBJECTIVES: To evaluate the anatomy, as well as the probability of restoring
      voice (study of the methods of vocal recovery) with the Newvox voice prosthesis.
      MATERIAL AND METHODS: This study relates to 225 patients having undergone a total
      laryngectomy and a Newvox voice prosthesis (one or more prosthesis) between April
      1979 and November 2003. All the cases were followed up for 2 years. During
      evolution the complications were noted. All the valves removed were sent for
      microbiological analysis, including culture. The Statistical Analysis were
      carried out on the cohort of patients defined as having benefited from one or
      more voice prostheses after undergoing total laryngectomy. The lifespan of the
      implants has been described by the median duration (corresponding to the duration
      above which 50% of the implants lasted) the first quartile (corresponding to the
      duration above which 75% of the implants lasted) and the third quartile
      (corresponding to the duration above which 25% of the implants lasted). RESULTS:
      No infection by candida albicans was found. Complete removal of the Newvox voice
      prosthesis for local problems was necessary only in 20 cases (8.9% of the cases).
      The general lifespan (on 225 patients) of the 1st implant corresponded to a
      median of 252 days (8.4 months) with a first quartile of 452 days (1.2 year). The
      statistical analysis of the lifespan of the Newvox voice prosthesis made it
      possible to study the impact of radiotherapy on the quality of the results. The
      time to onset of satisfactory phonation was studied: The general median (time
      above which includes 50% of the patients) was three weeks. After two weeks, 25%
      of the patients obtain a satisfactory voice. CONCLUSION: On the whole, out of 185
      documented cases, a satisfactory voice was obtained in 84% of patients, either by
      the voice prosthesis or by oesophageal voice. The absence of infection by candida
      albicans of the Newvox voice prosthesis is one of the factors which probably
      account for it being so well tolerated and having a significantly longer lifespan
      compared with other prostheses.

PMID- 18323329
TI  - [Prospective evaluation of the method of measurement of the peak nasal
      inspiratory flow (PNIF) in allergic rhinitis. Observational study "Pratic in
      ORL"].
AB  - OBJECTIVES: To establish the ENT specialists's interest for the nasal obstruction
      measurement by the Peak Nasal Inspiratory Flow (PNIF) for the primary care
      medical management of patients with allergic rhinitis. MATERIAL AND METHODS: A
      nation wide mail survey was conducted on the whole set of 2,800 French ENT
      specialists. Physicians had to use the PNIF in 4-consecutive patients with
      allergic rhinitis and assess through a questionnaire their interest for this
      tool. RESULTS: About 8% of all ENTs (n = 228) responded. 65.3% of them had used
      the PNIF with their 4 patients, 29.7% used it in only 1 to 3 of their patients,
      and 5% did not use it at all. The PNIF was mainly used in moderate to severe
      rhinitis (94%) in contrast with mild rhinitis (32%) and in persistent rhinitis
      (94.2%) compared to intermittent rhinitis (54.8%). The primary motivation to use
      the PNIF on a systematic basis was to quantitatively assess nasal obstruction and
      to obtain an objective measurement of nasal obstruction. Conversely, the reasons
      for not using the PNIF were the needless of an objective measurement of nasal
      obstruction, the drawback of the PNIF in the patient physician relationship and
      lack of patient's acceptance of the device. Most physicians considered training
      for a correct usage of the PNIF was easy. Finally, about 2 thirds of the sample
      gave a positive rating on the usefulness of the PNIF for their patients.
      CONCLUSION: This study demonstrates the interest of the practitioners to dispose
      of a simple and reliable tool for the follow up of nasal obstruction in allergic
      rhinitis.

PMID- 18323330
TI  - [Inflammatory pathology and rhinosinusal CT scan: the radiologist's report].
AB  - OBJECTIVE: Pave the way to a better management of the chronical rhino-sinusitis
      diseases: Description and classification of the chronical rhino-sinusitis
      pathology, its medical and surgical treatments in order to help the radiologist
      in its CT-scan report. MATERIAL AND METHOD: Review of the literature and
      anatomical considerations. Paranasal sinuses CT-scan analysis. RESULTS AND
      CONCLUSION: The execution and the interpretation of CT-scans, in accordance with
      the progress made in the past 20 years in the knowledge of the rhino-sinusitis
      physiology and pathology, are today absolutely necessary for the management of
      chronical rhino-sinusitis diseases.

PMID- 18323331
TI  - [Efficacy and safety of mometasone furoate nasal spray in the treatment of
      sinusitis or acute rhinosinusitis].
AB  - Sinusitis or acute rhinosinusitis, is defined as an acute viral or bacterial
      infection characterised by inflammation of the mucosa of the nose and paranasal
      sinuses. Although antibiotics are routinely prescribed for the treatment of acute
      sinusitis, most cases are caused by viral infections and will resolve without
      antibiotic therapy. Given concerns about global antibacterial resistance,
      evidence-based clinical practice guidelines recommend a conservative approach to
      antibiotic treatment, with mild or moderately severe acute sinusitis managed
      symptomatically. Intranasal corticosteroids act on the nasal mucosa to relieve
      inflammation and its associated symptoms, and may be a useful symptomatic
      treatment option. Two randomised, placebo-controlled trials have demonstrated
      that the corticosteroid mometasone furoate, administered as a nasal spray (MFNS),
      is effective as an adjunct to antibiotics in acute sinusitis. The design of these
      studies show a therapeutic approach known in Europe, but this attitude is still
      different from the current French guidelines. Furthermore, the efficacy and
      safety of MFNS monotherapy has been compared with antibiotic therapy in a
      randomised, double-blind, placebo-controlled trial in adults with acute
      uncomplicated sinusitis and probably viral. In this study, twice-daily (BID) MFNS
      200 microg produced statistically greater improvements in overall symptoms and
      most individual symptoms compared with amoxicillin or placebo, even though
      Amoxicillin is not the one recommended by the French guidelines for this
      indication. These findings suggest that MFNS may play an important role in the
      management of acute sinusitis, either as monotherapy or as adjunctive treatment
      to antibiotics. These results lead also to think over its interest in the
      treatment of uncomplicated common forms of sinusitis, where antibiotics are still
      widely prescribed in daily practice.

PMID- 18323332
TI  - [Primary nasal tuberculosis: a case report].
AB  - We report a case of a 36 year old woman who presented a chronic rhinitis and a
      hypertrophy of the inferior turbinates. Primary nasal tuberculosis was discovered
      by chance after the inferior turbinectomy. Primary nasal tuberculosis is very
      rare and is more frequent in women. Symptomatology is often unilateral with nasal
      obstruction, anterior rhinorrhea or epistaxis. The clinical examination may
      discover ulceration or a polyp located generally in the nasal septum or the
      inferior turbinate. Diagnosis relies on the anatomopathologic and bacteriological
      examinations. The treatment is mainly medical based on antituberculosis drugs. In
      the light of this case report, a review of the literature was made.

PMID- 18323333
TI  - Spontaneous perforation in the upper oesophagus resulting from ulcer in
      heterotopic gastric mucosa.
AB  - Heterotopic gastric mucosa (HGM) can be found throughout the entire
      gastrointestinal tract, more frequently in the cervical oesophagus. Macroscopic
      HGM is named inlet patch (IP). The great majority of IPs are asymptomatic and
      discovered incidently during oesophageal endoscopy performed for another
      pathology. However, complications can occur. Among these, perforation is
      extremely rare. We report a case of a 27-year old man who presented with a
      perforation of an upper oesophageal ulcer arising from an IP. The diagnosis was
      made during endoscopy and confirmed with biopsy of the tissue surrounding the
      perforation, showing histologic modifications consistent with heterotopic gastric
      mucosa. Medical treatment using a proton pump inhibitor and antibiotics delivered
      with a gastric tube was advocated. The perforation was closed at day 7 and plasma
      Argon coagulation of the inlet patch was performed two months later. Annual
      endoscopy has been normal for three years.

PMID- 18323334
TI  - [Sequelae of a fist blow. Nose completely tight].

PMID- 18323335
TI  - [Transmission of common cold. Does handshake make sick?] [interview by Dr. Judith
      Neumaier].

PMID- 18323336
TI  - [The many facets of rosacea. Illness in the red face].

PMID- 18323337
TI  - [From dry eye to keratitis. Often overlooked: ocular rosacea] [interview by
      Waldtraud Paukstadt].

PMID- 18323338
TI  - [Addiction therapy in family practice. The patient determines the tempo].

PMID- 18323339
TI  - [After vacation in the tropics. Whence comes the fever?].

PMID- 18323340
TI  - [Treatment of knee osteoarthritis].

PMID- 18323341
TI  - [Case report: small intestine invagination in a 61-year old patient].

PMID- 18323342
TI  - [Prevention of needle-stick injuries].

PMID- 18323343
TI  - [Fractures of the proximal humerus].

PMID- 18323344
TI  - [Importance of a fixed combination of AT1-receptor blockade and
      hydrochlorothiazide for blood pressure lowering in cardiac risk patients. A
      postmarketing surveillance study with candesartan/HCTZ].

PMID- 18323345
TI  - [Rupture of the rotator cuff].

PMID- 18323347
TI  - Reducing health disparities: every PA's obligation.

PMID- 18323346
TI  - [Headaches in the elderly].

PMID- 18323348
TI  - Painful sores in a young boy's mouth. Herpetic stomatitis.

PMID- 18323349
TI  - A day in the life.

PMID- 18323350
TI  - Diagnosis and management of patients with Marfan syndrome.

PMID- 18323351
TI  - An uncommon diagnosis in a young woman with knee pain. Synovial
      osteochondromatosis.

PMID- 18323352
TI  - Using yoga to treat disease: an evidence-based review.

PMID- 18323353
TI  - Understanding the idiopathic inflammatory myopathies.

PMID- 18323354
TI  - Managing the febrile infant: what is the standard of care?

PMID- 18323355
TI  - Tracking patients and outcomes.

PMID- 18323356
TI  - When a competent elderly man refuses nursing home placement.

PMID- 18323357
TI  - A 13-year-old boy with a common athletic injury. Avulsion fracture of the pelvis.

PMID- 18323358
TI  - Case of the month. Pitted keratolysis.

PMID- 18323359
TI  - Encouraging intellectual challenge and debate.

PMID- 18323360
TI  - Exploring prayer as a spiritual modality.
AB  - BACKGROUND: What does it mean to focus on the spiritual in occupational therapy?
      What interventions would qualify as spiritual modalities? This paper attempts to
      define the boundaries of what may be considered legitimate uses of spirituality
      in occupational therapy by using the example of prayer. PURPOSE: The purpose of
      this paper was to provide an in-depth analysis of the use of prayer in practice.
      METHOD: Medical and allied health journals were searched using the terms
      spirituality, spirit, religion, and prayer. Identified articles were synthesized
      to identify potential advantages and disadvantages of using prayer in therapy.
      FINDINGS: Prayer can be considered an appropriate occupational therapy
      intervention so long as four questions can be answered positively. IMPLICATIONS:
      To answer these questions, guidelines are provided that will lead the therapist
      through a decision making process to determine the appropriateness of
      incorporating prayer into any clinical situation.

PMID- 18323361
TI  - The dangers of thin air: a commentary on exploring prayer as a spiritual
      modality.

PMID- 18323362
TI  - Morality preempts modality: a commentary on exploring prayer as a spiritual
      modality.

PMID- 18323363
TI  - Considering ideology, context and client-centred language: a commentary on
      exploring prayer as a spiritual modality.

PMID- 18323364
TI  - "Circle of caring": a First Nations worldview of child rearing.
AB  - BACKGROUND: For occupational therapy to be meaningful for all families who have a
      child with a developmental disability, the profession needs to consider and
      integrate into practice alternative and more inclusive epistemologies. A greater
      understanding and respect of a First Nations worldview may help reduce the risk
      of inadvertently perpetuating oppression and assimilation. PURPOSE: To describe
      raising a child with a developmental disability from the perspective of five
      members of the Lil'wat Nation. METHODS: Data were obtained from in-depth
      interviews and analysed using a constant comparative approach. FINDINGS: Within
      the category of family the subcategories identified were extensive support
      network, intergenerational learning and doing, and influence of the residential
      school system. Within the category of raising a child the subcategories
      identified were health and spirituality, causation beliefs, and a sense of
      knowing. IMPLICATIONS: Occupational therapists need to be cognizant of
      alternative worldviews on child rearing, family, and health that may differ
      significantly from their own personal and professional beliefs and practices.

PMID- 18323365
TI  - Enabling occupation through facilitating the diagnosis of developmental
      coordination disorder.
AB  - BACKGROUND: The largest proportion of children seen within school-based
      occupational therapy is referred for handwriting difficulties. Many of these
      children have Developmental Coordination Disorder (DCD), a disorder that often
      goes undiagnosed, making if difficult for children, parents, and teachers to
      access resources. PURPOSE: The purpose of this article is to outline the
      important role of occupational therapists in recognizing and facilitating the
      diagnosis of DCD. KEY ISSUES: In this paper, a case is made for an expansion of
      the role of school-based occupational therapists in facilitating diagnosis for
      children with DCD. Through a review of the literature, we establish the
      importance of a diagnosis for children and families and critically reflect on
      issues that may make therapists reluctant to become involved in facilitating this
      diagnosis. IMPLICATIONS: Occupational therapists working in schools are able to
      recognize children with DCD, an important first step in accessing key resources
      useful to improve occupational performance and quality of life.

PMID- 18323366
TI  - Prevalence and correlates of low back pain among occupational therapy students in
      Northern Queensland.
AB  - BACKGROUND: Although low back pain (LBP) is an important issue for the health
      profession, few studies have examined LBP among occupational therapy students.
      PURPOSE: To investigate the prevalence and distribution of LBP, its adverse
      sequelae; and to identify potential risk factors. METHODS: In 2005, a self
      reported questionnaire was administered to occupational therapy students in
      Northern Queensland. FINDINGS: The 72-month period-prevalence of LBP was 64.6%.
      Nearly half (46.9%) had experienced pain for over 2 days, 38.8% suffered LBP that
      affected their daily lives, and 24.5% had sought medical treatment. The
      prevalence of LBP ranged from 45.5 to 77.1% (p = 0.004), while the prevalence of
      LBP symptoms persisting longer than two days was 34.1 to 62.5% (p = 0.020).
      Logistic regression analysis indicated that year of study and weekly computer
      usage were statistically-significant LBP risk factors. IMPLICATIONS: The
      occupational therapy profession will need to further investigate the high
      prevalence of student LBP identified in this study.

PMID- 18323367
TI  - Education, collaboration and core set development.

PMID- 18323368
TI  - Intraprofessional fieldwork education: occupational therapy and occupational
      therapist assistant students learning together.
AB  - BACKGROUND: In the past 10 years, the use of support personnel in Canada has
      generated significant interest from occupational therapists, professional
      associations, regulatory bodies, employers, educational institutions, and
      government agencies. PURPOSE: The purpose of this study was to explore the impact
      of a combined collaborative fieldwork placement and weekly tutorial as a teaching
      strategy for intraprofessional education. METHODS: Seven pairs of student
      occupational therapists and occupational therapist assistants were assigned to
      fieldwork placements. Tutorials were scheduled during the placements to discuss
      intraprofessional issues and provision of occupational therapy services in the
      clinical setting. Journaling and focus groups were used to collect data from
      students, tutors, and preceptors. FINDINGS: Three key themes emerged from the
      data: (1) developing the relationship, (2) understanding roles, and (3)
      recognizing environmental influences on learning. IMPLICATIONS: Intraprofessional
      learning experiences prior to graduation can help prepare occupational therapy
      and occupational therapist assistant students for future collaborative practice.

PMID- 18323369
TI  - Meeting the challenge of assessing clinical competence of occupational therapists
      within a program management environment.
AB  - BACKGROUND: Program management models have raised concerns among occupational
      therapists about professional standards related to clinical competence,
      performance review procedures, and quality improvement initiatives. PURPOSE: This
      paper describes how a chart-stimulated recall (CSR) peer-review process and
      interview tool was revised, implemented, and evaluated as a pilot project to
      assess the clinical competence of occupational therapy staff at a large urban
      health centre in southern Ontario. METHODS: Fourteen pairs (n=28) of occupational
      therapists representing various practice areas participated in this project. Half
      served as peer assessors and half as interviewees. Peer assessors conducted an
      independent chart review followed by a one-hour personal interview with a peer
      partner to discuss clinical management issues related to the client cases. Each
      interviewer rated his or her partner's clinical competence in eight areas of
      performance using a 7-point Likert scale. FINDINGS: Results indicated that the
      CSR tool could discriminate among occupational therapists in terms of overall
      levels of clinical competence and also identify specific areas of concern that
      could be targeted for professional development. Feedback from participants was
      positive. CONCLUSIONS: The CSR tool was found to be useful for assessing clinical
      competence of occupational therapists in this large health centre as a quality
      improvement initiative within that discipline group. Further research is needed
      to establish the reliability and validity of the CSR tool.

PMID- 18323370
TI  - Reflections on...well-being and occupational rights.
AB  - BACKGROUND: Although claiming that engagement in occupations influences well
      being, the occupational therapy profession has largely failed to acknowledge and
      address the relationships between well-being, occupation, and human rights.
      PURPOSE: This paper supports the premise that the focus of occupational therapy
      should be on the right of all people to participate in meaningful occupations,
      and proposes allegiance to occupational rights: the right of all people to engage
      in meaningful occupations that contribute positively to their own well-being and
      the well-being of their communities. PRACTICE IMPLICATIONS: The connection
      between well-being and human rights would be made explicit, occupational rights
      would be recognized as a political issue and the profession's confinement within
      health-care services would end. This commitment to occupational rights would
      bring our practice into line with our espoused belief in the relationship between
      occupation and well-being, and enable us to state, unequivocally, what
      occupational therapy contributes to humanity.

PMID- 18323371
TI  - The international polar year 2007-2008; the Arctic human health legacy.
AB  - Life expectancy in Arctic populations has greatly improved over the last 50
      years. Much of this improvement can be attributed to health research that has
      resulted in a reduction in morbidity and mortality from infectious diseases, such
      as tuberculosis, and the vaccine-preventable diseases of childhood. However,
      despite these improvements in health indicators of Arctic residents, life
      expectancy and infant mortality remain higher in indigenous Arctic residents in
      the US Arctic, northern Canada, and Greenland when compared to Arctic residents
      of Nordic countries. The International Polar Year (IPY) represents a unique
      opportunity to focus world attention on Arctic human health and to further
      stimulate Circumpolar cooperation on emerging Arctic human health concerns. The
      Arctic Human Health Initiative (AHHI) is an Arctic Council IPY initiative that
      aims to build and expand on existing Arctic Council and International Union for
      Circumpolar Health (IUCH) human health research activities. The human health
      legacy of the IPY will be increased visibility of the human health concerns of
      Arctic communities, revitalization of cooperative Arctic human health research
      focused on those concerns, the development of health policies based on research
      findings, and the subsequent implementation of appropriate interventions,
      prevention and control measures at the community level.

PMID- 18323372
TI  - The Alaska-Siberia medical program: 24 years in retrospect.
AB  - OBJECTIVES: The purpose of this paper is to give the reader some idea of life in
      Siberia and Alaska during the creation of our first medical exchanges during the
      most difficult of political times. STUDY DESIGN: Various projects were designed
      using National Institutes of Health (NIH) criteria for our medical exchange.
      METHODS: As we took these first steps between the Siberian Branch of the Academy
      of Medical Sciences of the USSR and the Institute for Circumpolar Health Studies
      at the University of Alaska Anchorage, USA, the general areas of our first
      studies were: (1) Circadian Rhythm and Work-Related Injuries in the North; (2)
      Alcohol and its Abuse with Treatment Methodologies; (3) Public Health
      Administration and Design in the Far East and Alaska; (4) Cystic Echinococcosis
      in the Arctic and Sub-Arctic; (5) Viral Hepatitis in the Arctic; (6) Cardiology;
      (7) Nutrition; and (8) Diabetes Prevention. RESULTS: A film made by the
      University of Alaska which was shown on PBS' "Breaking the Ice: The Alaska
      Siberia Medical Research Program"; various papers and books published on both
      sides; and a major contribution made to world peace through the medical workers
      on both sides of the Bering Sea. CONCLUSION: This major effort for peace showed
      the world how the peoples of Siberia and Alaska could come together and work for
      world peace through joint collaborations. Native people were reunited after years
      of separation, new avenues were created in anthropology, biology and medicine,
      and, subsequently, the border was again opened between our peoples.

PMID- 18323373
TI  - The family wellness warriors initiative.
AB  - Southcentral Foundation (SCF) is an Alaska Native 501(c) (3) non-profit
      healthcare organization established in 1982 by the Cook Inlet Region, Inc.
      (CIRI), which is one of thirteen Alaska Native regional corporations created by
      Congress in 1971 under the terms of the Alaska Native Claims Settlement Act. CIRI
      established SCF to improve the health and social conditions of Alaska Native
      people, enhance culture, and empower individuals and families to take charge of
      their lives. SCF is totally customer-owned and managed by the tribal authority of
      CIRI. Under the federal Indian Self Determination Act of Public Law 93-638 and
      Section 325, SCF provides health and human services to approximately 45,000
      residents within a geographical area of 107,413 square miles extending from the
      Canadian border on the east to the entire Aleutian Chain and Pribilof Islands on
      the west. SCF owns and manages primary care services, community services,
      behavioral health services, dental services, and residential treatment centers.
      Our funding sources are 45% Indian Health Service funding, 45% Medicare, Medicaid
      and private insurance, and 10% grants, contracts and research funding. SCF has
      experienced dramatic growth over the past fifteen years: the workforce increased
      from fewer than 100 to about 1300 employees, and the operating budget has grown
      from $3 million to $118 million. While managing nearly two decades of exponential
      growth, SCF distinguished itself as one of the nation's leading care providers
      for Alaska Native and American Indian people, launching such innovations as the
      nation's first fetal alcohol syndrome prevention program and implementing
      healthcare industry best practices such as a fully-integrated primary care system
      and system-wide "open access". SCF has drastically changed the healthcare system
      from a slow bureaucratic system to a customer-responsive, customer-owned and
      customer-driven healthcare system.

PMID- 18323374
TI  - Women's cancers among Alaska Natives: [corrected] 1969-2003.
AB  - INTRODUCTION: Alaska Native (AN) people include multiple, diverse ethnic groups
      whose ancestors occupied what is now the state of Alaska. Cancer incidence rates
      among Alaska Native women for breast, cervix, uterus and ovary are presented
      here. Current rates and trends over time are compared with U.S. White rates.
      OBJECTIVE: To describe cancer incidence patterns for cancer of the breast,
      cervix, uterus and ovary among Alaska Native women. METHODS: Cancer incidence
      data for Alaska Natives are from the Alaska Native Tumor Registry, in Anchorage,
      Alaska. Incidence rates for U.S. Whites are from the National Cancer Institute
      Surveillance, Epidemiology, and End Results Program. RESULTS: Breast and cervical
      cancer incidence rates among Alaska Natives are similar to U.S. White rates,
      whereas rates for cancer of the uterus and ovary are significantly less than
      those of U.S. Whites. Thirty-five year trends show increasing rates in breast
      cancer and decreasing rates of cervical cancer. CONCLUSION: The burden of cancer
      among Alaska Native women for cancers unique to women is significant. Increasing
      breast cancer rates among Alaska Natives has greatly contributed to this burden.

PMID- 18323375
TI  - Future health care in Alaska. 1975.

PMID- 18323376
TI  - Paralytic shellfish poisoning in the north Pacific: two historical accounts and
      implications for today. 1975.

PMID- 18323377
TI  - Will we ever see the end of mixed wards?

PMID- 18323378
TI  - 'The important symbols of nursing have not been eradicated--they have changed'.

PMID- 18323379
TI  - NHS nursing in the 1960s.

PMID- 18323380
TI  - Where training is valued. Interview by Jennifer Taylor.

PMID- 18323381
TI  - More action required to cut alcohol-related death rate.

PMID- 18323382
TI  - The sense of touch. Part 1--touch sensation.

PMID- 18323383
TI  - Pneumonia 2: effective nursing assessment and management.
AB  - Part 1 of this two-part unit on pneumonia explored common signs and symptoms of
      the infection, and explained how nurses can identify those at high risk. This
      part looks at its nursing assessment and management.

PMID- 18323384
TI  - Urine collection in infants and children.
AB  - June Rogers and Caroline Saunders review current evidence and best practice
      regarding obtaining a urine specimen from children.

PMID- 18323385
TI  - Vaginal cones in stress incontinence treatment.
AB  - Jeanette Haslam explains the theory that underpins the use of vaginal cones in
      stress urinary incontinence and how this translates into practice.

PMID- 18323386
TI  - Nurse prescribing: national data analysis.
AB  - Kathy Davis and Vari Drennan summarise the results of an investigation into the
      prescribing behaviours of community-based nurses and GPs, using prescribing in
      constipation as a case study (Davis and Drennan, 2007).

PMID- 18323387
TI  - Reducing admissions for urinary catheterisation.
AB  - Sandra Foulkes describes a service development that reduced emergency admissions
      for urinary catheter-related problems through collaborative working and community
      catheter clinics. This will be supported by the use of a case study.

PMID- 18323388
TI  - The language of healthcare. Variance in the English language is harming patients
      and hospitals' bottom lines. Is healthcare IT the solution?

PMID- 18323389
TI  - The speed to know. The convergence of biomedical devices and IT for the ED may
      lead to improved patient care.

PMID- 18323390
TI  - What gets measured gets managed.

PMID- 18323391
TI  - Consent Redux. An Illinois medical center moves from paper to automated informed
      consent to meet regulatory compliance, reduce errors and facilitate
      communication.

PMID- 18323392
TI  - Autonomous information handling. New technology replicates information handling
      intelligence into small applications, benefiting a multihospital system in
      Michigan.

PMID- 18323393
TI  - From the ground up. This family practice's preopening installation of an
      integrated PM/EMR streamlined billing and increased profitability.

PMID- 18323394
TI  - Strategic placement. Addressing the data explosion in healthcare requires a sound
      strategy for turning data into information.

PMID- 18323395
TI  - Answering the call. An EMS replaces a modem-based dispatch system with a wireless
      technology solution, improving response times with actionable information.

PMID- 18323396
TI  - The supporting player. Second generation CDS goes beyond the basics to become
      intuitive.

PMID- 18323397
TI  - When consistency counts. Now that medication reconciliation has become a mandate,
      healthcare organizations are looking for effective ways to implement it, and for
      some, the answer is information technology.

PMID- 18323398
TI  - RHIOs in reverse.

PMID- 18323399
TI  - Improve your presentation skills with these tips.

PMID- 18323400
TI  - Insurance, celebrities may shape endoscopic market.

PMID- 18323401
TI  - Tips to help craft a meaningful, targeted data report.

PMID- 18323402
TI  - Pharmacological and clinical aspects of heme oxygenase.
AB  - This review is intended to stimulate interest in the effect of increased
      expression of heme oxygenase-1 (HO-1) protein and increased levels of HO activity
      on normal and pathological states. The HO system includes the heme catabolic
      pathway, comprising HO and biliverdin reductase, and the products of heme
      degradation, carbon monoxide (CO), iron, and biliverdin/bilirubin. The role of
      the HO system in diabetes, inflammation, heart disease, hypertension,
      neurological disorders, transplantation, endotoxemia and other pathologies is a
      burgeoning area of research. This review focuses on the clinical potential of
      increased levels of HO-1 protein and HO activity to ameliorate tissue injury. The
      use of pharmacological and genetic probes to manipulate HO, leading to new
      insights into the complex relationship of the HO system with biological and
      pathological phenomena under investigation, is reviewed. This information is
      critical in both drug development and the implementation of clinical approaches
      to moderate and to alleviate the numerous chronic disorders in humans affected by
      perturbations in the HO system.

PMID- 18323403
TI  - In vitro induction of natural killer T cells from embryonic stem cells prepared
      using somatic cell nuclear transfer.
AB  - The ectopic expression of the Notch receptor ligand delta-like 1 on stromal cells
      allows the induction of T cells from embryonic stem cells (ESCs). However, these
      in vitro-generated T cells are not transplantable because they are too immature
      to mount an immune response in an immunocompromised animal. We efficiently
      generated a subset of T cells called invariant natural killer T (iNKT) cells from
      ESCs derived from peripheral iNKT cells using somatic cell nuclear transfer
      (ntESCs). These iNKT cells matured autonomously in vivo and exhibited an adjuvant
      effect accompanying the production of interferon-gamma in an antigen-specific
      manner. This adjuvant effect culminated in the inhibition of inoculated tumor
      cell growth. Our results indicate that ntESC-derived iNKT cells are
      transplantable lymphocytes that will be beneficial for the induction of immune
      tolerance and the treatment of autoimmune diseases, tumors, and infections.

PMID- 18323404
TI  - A genome-wide survey suggests an osmoprotective role for vacuolar Ca2+ release in
      cell wall-compromised yeast.
AB  - In yeast, osmotic upshock causes a release of vacuolar Ca(2+) through the
      mechanosensitive transient receptor potential channel, Yvc1. We screened the
      collection of 4810 yeast gene deletants twice for alterations in this response in
      an attempt to find elements that regulate the amount of vacuolar Ca(2+) or the
      Yvc1 channel. Severe overresponders and underresponders to upshock were further
      scrutinized for their calcium content with (45)Ca and their Yvc1
      electrophysiological activities under patch-clamp. The severe underresponders
      have lower calcium content but no change in Yvc1 activity. The strong
      overresponders, most of which are deleted of genes involved in cell wall
      metabolism, have higher calcium content. Wall mutations are known to up-regulate
      Ca(2+)-calcineurin-dependent genes. It appears that stress on the cell wall
      induces Ca(2+) accumulation, adaptively anticipating the need in defense or
      repair against future stress, including osmotic stress.

PMID- 18323405
TI  - Neuropeptide Y is produced in visceral adipose tissue and promotes proliferation
      of adipocyte precursor cells via the Y1 receptor.
AB  - Neuropeptide Y (NPY) is synthesized in neural tissue of the central and
      peripheral nervous systems and has a number of important functions besides
      regulating appetite and energy homeostasis. Here we identify a novel site of NPY
      biosynthesis and a role for NPY in promoting proliferation of adipocyte precursor
      cells. We show that NPY mRNA is not only expressed in visceral adipose tissue
      (VAT) but that its levels are up-regulated 6-fold in our early-life programmed
      rat model of increased visceral adiposity. This is accompanied by a parallel rise
      in NPY protein, demonstrating that VAT is a novel peripheral site of NPY
      biosynthesis. Furthermore, NPY mRNA expression is also elevated >2-fold in VAT of
      obese Zucker rats. Importantly, NPY stimulates proliferation of primary rat
      preadipocytes as well as 3T3-L1 preadipocytes in vitro. This mitogenic effect
      appears to be mediated by the Y1 receptor and involves the activation of
      extracellular related kinase 1/2. In addition, insulin and glucocorticoid up
      regulate VAT NPY expression in lean but not obese Zucker rats. Taken together,
      these results suggest that an enhanced local expression of NPY within VAT may be
      a common feature of and contribute to the molecular mechanisms underlying
      increased visceral adiposity.

PMID- 18323406
TI  - BAF250B-associated SWI/SNF chromatin-remodeling complex is required to maintain
      undifferentiated mouse embryonic stem cells.
AB  - Whether SWI/SNF chromatin remodeling complexes play roles in embryonic stem (ES)
      cells remains unknown. Here we show that SWI/SNF complexes are present in mouse
      ES cells, and their composition is dynamically regulated upon induction of ES
      cell differentiation. For example, the SWI/SNF purified from undifferentiated ES
      cells contains a high level of BAF155 and a low level of BAF170 (both of which
      are homologs of yeast SWI3 protein), whereas that from differentiated cells
      contains nearly equal amounts of both. Moreover, the levels of BAF250A and
      BAF250B decrease during the differentiation of ES cells, whereas that of BRM
      increases. The altered expression of SWI/SNF components hinted that these
      complexes could play roles in ES cell maintenance or differentiation. We
      therefore generated ES cells with biallelic inactivation of BAF250B and found
      that these cells display a reduced proliferation rate and an abnormal cell cycle.
      Importantly, these cells are deficient in the self-renewal capacity of
      undifferentiated ES cells and exhibit certain phenotypes of differentiated cells,
      including reduced expression of several pluripotency-related genes and increased
      expression of some differentiation-related genes. These data suggest that the
      BAF250B-associated SWI/SNF is essential for mouse ES cells to maintain their
      normal proliferation and pluripotency. The work presented here underscores the
      importance of SWI/SNF chromatin remodeling complexes in pluripotent stem cells.

PMID- 18323407
TI  - Instability of retroviral DNA methylation in embryonic stem cells.
AB  - The epigenetic status of pluripotent stem cells has been demonstrated to be
      extremely unstable. In our current study, we have attempted to further
      investigate the epigenetic dynamics of the stem cell genome by monitoring the
      expression of the murine stem cell virus (MSCV) retroviral vector in embryonic
      stem (ES) cells. Although MSCV is progressively silenced by proviral DNA
      methylation in ES cells, a substantial number of MSCV-transduced ES cell clones
      do show variegated proviral expression. This expression profile is due in part to
      the transient and reversible properties of MSCV silencing. However, the
      spontaneous reactivation rates of the silenced proviruses differ significantly
      between these variegated clones, indicating that the reversibility of silencing
      is dependent on the proviral integration site. Our current data suggest that the
      fidelity of DNA methylation among the genomic sequences that flank the proviral
      integration sites may be the determinant of this reversibility of MSCV silencing.
      Given that the adjoining epigenome environment affects the epigenetic regulation
      of proviral DNA, the reversible MSCV silencing effect is thus likely to reflect a
      unique and interesting feature of ES cell epigenome regulation that has not
      previously been revealed.

PMID- 18323408
TI  - Nuclear magnetic resonance metabolomic footprinting of human hepatic stem cells
      and hepatoblasts cultured in hyaluronan-matrix hydrogels.
AB  - Human hepatoblasts (hHBs) and human hepatic stem cells (hHpSCs) were maintained
      in serum-free Kubota's medium, a defined medium tailored for hepatic progenitors,
      and on culture plastic versus hyaluronan hydrogels mixed with specific
      combinations of extracellular matrix components (e.g., type I collagen and
      laminin). Nuclear magnetic resonance spectroscopy was used to define metabolomic
      profiles for each substratum tested. The hHpSCs on culture plastic survived
      throughout the culture study, whereas hHBs on plastic died within 7-10 days. Both
      survived and expanded in all hydrogel-matrix combinations tested for more than 4
      weeks. Profiles of hundreds of metabolites were narrowed to a detailed analysis
      of eight, such as glucose, lactate, and glutamine, shown to be significant
      components of cellular pathways, including the Krebs and urea cycles. The
      metabolomic profiles indicated that hHpSCs on plastic remained as stem cells
      expressing low levels of albumin but no alpha-fetoprotein (AFP); those in
      hydrogels were primarily hHBs, expressing AFP, albumin, and urea. Both hHpSCs and
      hHBs used energy provided by anaerobic metabolism. Variations in hyaluronan
      matrix chemistry resulted in distinct profiles correlating with growth or with
      differentiative responses. Metabolomic footprinting offers noninvasive and
      nondestructive assessment of physiological states of stem/progenitor cells ex
      vivo. Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 18323409
TI  - Nucleofection mediates high-efficiency stable gene knockdown and transgene
      expression in human embryonic stem cells.
AB  - High-efficiency genetic modification of human embryonic stem (hES) cells would
      enable manipulation of gene activity, routine gene targeting, and development of
      new human disease models and treatments. Chemical transfection, nucleofection,
      and electroporation of hES cells result in low transfection efficiencies. Viral
      transduction is efficient but has significant drawbacks. Here we describe
      techniques to transiently and stably express transgenes in hES cells with high
      efficiency using a widely available vector system. The technique combines
      nucleofection of single hES cells with improved methods to select hES cells at
      clonal density. As validation, we reduced Oct4 and Nanog expression using siRNAs
      and shRNA vectors in hES cells. Furthermore, we derived many hES cell clones with
      either stably reduced alkaline phosphatase activity or stably overexpressed green
      fluorescent protein. These clones retained stem cell characteristics (normal
      karyotype, stem cell marker expression, self-renewal, and pluripotency). These
      studies will accelerate efforts to interrogate gene function and define the
      parameters that control growth and differentiation of hES cells. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 18323410
TI  - A comparison of protocols used to generate insulin-producing cell clusters from
      mouse embryonic stem cells.
AB  - Embryonic stem cells (ESCs) have the capacity to generate a panoply of tissue
      types and may therefore provide an alternative source of tissue in regenerative
      medicine to treat potentially debilitating conditions like Type 1 diabetes
      mellitus. However, the ability of mouse ESCs to generate insulin-producing cell
      clusters (IPCCs) remains highly contentious. In an attempt to clarify this issue,
      three protocols for the ESC-based generation of IPCCs (referred to as Blyszczuk,
      Hori, and Lumelsky protocols) were modified and evaluated for their ability to
      express pancreatic islet genes and proteins and their capacity to function.
      Herein, we show that the Blyszczuk protocol reproducibly generated IPCCs with
      gene-expression characteristics that were qualitatively and quantitatively most
      reminiscent of those found in pancreatic islets. Furthermore, compared to the
      Hori and Lumelsky protocols, Blyszczuk-derived IPCCs exhibited superior
      expression of c-peptide, a by-product of de novo insulin synthesis. Functionally,
      Blyszczuk IPCCs, in contrast to Hori and Lumelsky IPCCs, were able to transiently
      restore normal blood glucose levels in diabetic mice (<1 week). Longer
      normoglycemic rescue (>2 weeks) was also achieved in a third of diabetic
      recipients receiving Blyszczuk IPCCs. Yet Blyszczuk IPCCs were less able to
      rescue experimental diabetes than isolated syngeneic pancreatic islet tissue.
      Therefore, depending on the mode of differentiation, ESCs can be driven to
      generate de novo IPCCs that possess limited functionality. Further modifications
      to differentiation protocols will be essential to improve the generation of
      functional IPCCs from mouse ESCs.

PMID- 18323411
TI  - Glycogen synthase kinase-3beta inhibition preserves hematopoietic stem cell
      activity and inhibits leukemic cell growth.
AB  - Ex vivo expansion of cord blood cells generally results in reduced stem cell
      activity in vivo. Glycogen synthase kinase-3beta (GSK-3beta) regulates the
      degradation of beta-catenin, a critical regulator of hematopoietic stem cells
      (HSCs). Here we show that GSK-3beta inhibition activates beta-catenin in cord
      blood CD34(+) cells and upregulates beta-catenin transcriptional targets c-myc
      and HoxB4, both known to regulate HSC self-renewal. GSK-3beta inhibition resulted
      in delayed ex vivo expansion of CD34(+) cells, yet enhanced the preservation of
      stem cell activity as tested in long-term culture with bone marrow stroma.
      Delayed cell cycling, reduced apoptosis, and increased adherence of hematopoietic
      progenitor cells to bone marrow stroma were observed in these long-term cultures
      treated with GSK-3beta inhibitor. This improved adherence to stroma was mediated
      via upregulation of CXCR4. In addition, GSK-3beta inhibition preserved severe
      combined immunodeficiency (SCID) repopulating cells as tested in the nonobese
      diabetic/SCID mouse model. Our data suggest the involvement of GSK-3beta
      inhibition in the preservation of HSC and their interaction with the bone marrow
      environment. Methods for the inhibition of GSK-3beta may be developed for
      clinical ex vivo expansion of HSC for transplantation. In addition, GSK-3beta
      inhibition suppressed leukemic cell growth via the induction of apoptosis
      mediated by the downregulation of survivin. Modulators of GSK-3beta may increase
      the range of novel drugs that specifically kill leukemic cells while sparing
      normal stem cells.

PMID- 18323412
TI  - Induction of neurogenesis in nonconventional neurogenic regions of the adult
      central nervous system by niche astrocyte-produced signals.
AB  - The central nervous system (CNS) of adult mammals regenerates poorly; in vivo,
      neurogenesis occurs only in two restricted areas, the hippocampal subgranular
      zone (SGZ) and the subventricular zone (SVZ). Neurogenic potential depends on
      both the intrinsic properties of neural progenitors and the environment, or
      niche, in which progenitor cells reside. Isolation of multipotent progenitor
      cells from broad CNS regions suggests that the neurogenic potential of the adult
      CNS is dictated by local environmental cues. Here, we report that astrocytes in
      the neurogenic brain regions, the SGZ and SVZ, of adult mice release molecular
      signals, such as sonic hedgehog (Shh), that stimulate adult neural progenitors to
      reenter the cell cycle and generate new neurons in vitro and in vivo.
      Transplantation of SGZ astrocytes or application of Shh caused de novo
      neurogenesis from the non-neurogenic neocortex of adult mice. These findings
      identify a molecular target that can activate the dormant neurogenic potential
      from nonconventional neurogenic regions of the adult CNS and suggest a novel
      mechanism of neural replacement therapy for treating neurodegenerative disease
      and injury without transplanting exogenous cells.

PMID- 18323413
TI  - Reproductive steroid hormones and recurrence-free survival in women with a
      history of breast cancer.
AB  - Epidemiologic studies fairly consistently show in postmenopausal women that
      reproductive steroid hormones contribute to primary breast cancer risk, and this
      association is strongly supported by experimental studies using laboratory
      animals and model systems. Evidence linking sex hormone concentrations with risk
      for recurrence in women diagnosed with breast cancer is limited; however,
      beneficial effects of antiestrogenic therapy on recurrence-free survival suggest
      that these hormones affect progression and risk for recurrence. This study
      examined whether baseline serum concentrations of estradiol, testosterone, and
      sex hormone binding globulin were associated with recurrence-free survival in a
      nested case-control cohort of women from a randomized diet trial (Women's Healthy
      Eating and Living Study) who were followed for >7 years after diagnosis. In 153
      case-control pairs of perimenopausal and postmenopausal women in this analysis,
      total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration;
      95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26;
      95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65)
      concentrations were significantly associated with risk for recurrence. Recurred
      women had an average total estradiol concentration that was double that of
      nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex
      hormone binding globulin concentrations did not differ between cases and controls
      and were not associated with risk for recurrence. Although genetic and metabolic
      factors likely modulate the relationship between circulating sex hormones and
      risk, results from this study provide evidence that higher serum estrogen
      concentration contributes to risk for recurrence in women diagnosed with early
      stage breast cancer.

PMID- 18323414
TI  - Endogenous galectin-1 enforces class I-restricted TCR functional fate decisions
      in thymocytes.
AB  - During thymocyte development, the T-cell receptor (TCR) can discriminate major
      histocompatibility complex (MHC)/peptide ligands over a narrow range of
      affinities and translate subtle differences into functional fate decisions. How
      small differences in TCR input are translated into absolute differences in
      functional output is unclear. We examined the effects of galectin-1 ablation in
      the context of class-I-restricted thymocyte development. Galectin-1 expression
      opposed TCR partial agonist-driven positive selection, but promoted TCR agonist
      driven negative selection of conventional CD8(+) T cells. Galectin-1 expression
      also promoted TCR agonist-driven CD8alphaalpha intestinal intraepithelial
      lymphocytes (IEL) development. Recombinant galectin-1 enhanced TCR binding to
      agonist/MHC complexes and promoted a negative-selection-signaling signature,
      reflected in intensified rapid and transient extracellular signal-regulated
      kinase (ERK) activation. In contrast, galectin-1 expression antagonized ERK
      activity in thymocytes undergoing positive selection. We propose that galectin-1
      aids in discriminating TCR-directed fate decisions by promoting TCR binding to
      agonist/MHC complexes and enforcing agonist-driven signals, while opposing
      partial-agonist signals. In this way, galectin-1 widens the distinction between
      TCR-directed functional fate cues.

PMID- 18323415
TI  - Frequency ratio of Al+ and Hg+ single-ion optical clocks; metrology at the 17th
      decimal place.
AB  - Time has always had a special status in physics because of its fundamental role
      in specifying the regularities of nature and because of the extraordinary
      precision with which it can be measured. This precision enables tests of
      fundamental physics and cosmology, as well as practical applications such as
      satellite navigation. Recently, a regime of operation for atomic clocks based on
      optical transitions has become possible, promising even higher performance. We
      report the frequency ratio of two optical atomic clocks with a fractional
      uncertainty of 5.2 x 10(-17). The ratio of aluminum and mercury single-ion
      optical clock frequencies nuAl+/nuHg+ is 1.052871833148990438(55), where the
      uncertainty comprises a statistical measurement uncertainty of 4.3 x 10(-17), and
      systematic uncertainties of 1.9 x 10(-17) and 2.3 x 10(-17) in the mercury and
      aluminum frequency standards, respectively. Repeated measurements during the past
      year yield a preliminary constraint on the temporal variation of the fine
      structure constant alpha of alpha/alpha = (-1.6+/-2.3) x 10(-17)/year.

PMID- 18323416
TI  - Oncogenic CARD11 mutations in human diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's
      lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant
      cells is dependent on constitutive activation of the nuclear factor-kappaB (NF
      kappaB) signaling pathway. In normal B cells, antigen receptor-induced NF-kappaB
      activation requires CARD11, a cytoplasmic scaffolding protein. To determine
      whether CARD11 contributes to tumorigenesis, we sequenced the CARD11 gene in
      human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies
      (9.6%), all within exons encoding the coiled-coil domain. Experimental
      introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines
      resulted in constitutive NF-kappaB activation and enhanced NF-kappaB activity
      upon antigen receptor stimulation. These results demonstrate that CARD11 is a
      bona fide oncogenein DLBCL, providing a genetic rationale for the development of
      pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.

PMID- 18323417
TI  - Linked reactivity at mineral-water interfaces through bulk crystal conduction.
AB  - The semiconducting properties of a wide range of minerals are often ignored in
      the study of their interfacial geochemical behavior. We show that surface
      specific charge density accumulation reactions combined with bulk charge carrier
      diffusivity create conditions under which interfacial electron transfer reactions
      at one surface couple with those at another via current flow through the crystal
      bulk. Specifically, we observed that a chemically induced surface potential
      gradient across hematite (alpha-Fe2O3) crystals is sufficiently high and the bulk
      electrical resistivity sufficiently low that dissolution of edge surfaces is
      linked to simultaneous growth of the crystallographically distinct (001) basal
      plane. The apparent importance of bulk crystal conduction is likely to be
      generalizable to a host of naturally abundant semiconducting minerals playing
      varied key roles in soils, sediments, and the atmosphere.

PMID- 18323419
TI  - A new Editor-in-Chief.

PMID- 18323418
TI  - A model for neuronal competition during development.
AB  - We report that developmental competition between sympathetic neurons for survival
      is critically dependent on a sensitization process initiated by target
      innervation and mediated by a series of feedback loops. Target-derived nerve
      growth factor (NGF) promoted expression of its own receptor TrkA in mouse and rat
      neurons and prolonged TrkA-mediated signals. NGF also controlled expression of
      brain-derived neurotrophic factor and neurotrophin-4, which, through the receptor
      p75, can kill neighboring neurons with low retrograde NGF-TrkA signaling whereas
      neurons with high NGF-TrkA signaling are protected. Perturbation of any of these
      feedback loops disrupts the dynamics of competition. We suggest that three target
      initiated events are essential for rapid and robust competition between neurons:
      sensitization, paracrine apoptotic signaling, and protection from such effects.

PMID- 18323420
TI  - Natural disasters. Ecologists report huge storm losses in China's forests.

PMID- 18323421
TI  - Animal rights. Brazilian scientists battle animal experimentation bans.

PMID- 18323422
TI  - Physics. Test of Hawking's prediction on the horizon with mock 'white hole'.

PMID- 18323423
TI  - Large facilities. NSF delays three projects to get better handle on costs.

PMID- 18323424
TI  - Research funding. U.S. biomedicine's mother ship braces for lab closings.

PMID- 18323425
TI  - Space physics. Antimatter experiment may be too costly for NASA to launch.

PMID- 18323427
TI  - Near-Earth objects. Preparing for Doomsday.

PMID- 18323426
TI  - Planetary science. Electron shadow hints at invisible rings around a moon.

PMID- 18323428
TI  - Near-Earth objects. The state of our planet's defenses.

PMID- 18323429
TI  - Paleontology. Experts find no evidence for a mammoth-killer impact.

PMID- 18323430
TI  - Plant sciences. Corn genomics pops wide open.

PMID- 18323431
TI  - Rewarding reviewers.

PMID- 18323432
TI  - Rating reviewers.

PMID- 18323433
TI  - Preventing inequity in international research.

PMID- 18323434
TI  - Comment on "Early Archaean microorganisms preferred elemental sulfur, not
      sulfate".
AB  - Philippot et al. (Reports, 14 September 2007, p. 1534) interpreted multiple
      sulfur isotopic compositions of approximately 3.5-billion-year-old marine sulfide
      deposits as evidence that early Archaean microorganisms were not sulfate reducers
      but instead metabolized elemental sulfur. However, their data can be better
      explained by a scenario involving poor mixing of photochemical and surface
      sulfide sources.

PMID- 18323435
TI  - AIDS vaccine research: consider co-infections.

PMID- 18323436
TI  - Medicine. Moving toward transparency of clinical trials.

PMID- 18323437
TI  - Geology. Canyon cutting on a grand time scale.

PMID- 18323438
TI  - Molecular biology. A tail tale for U.

PMID- 18323439
TI  - Behavior. Punishment and cooperation.

PMID- 18323440
TI  - Oceans. On phytoplankton trends.

PMID- 18323441
TI  - Signal transduction. Sweet conundrum.

PMID- 18323442
TI  - Computer science. Science 2.0.

PMID- 18323443
TI  - Retrospective: Joshua Lederberg (1925-2008).

PMID- 18323444
TI  - An oncogene-induced DNA damage model for cancer development.
AB  - Of all types of DNA damage, DNA double-strand breaks (DSBs) pose the greatest
      challenge to cells. One might have, therefore, anticipated that a sizable number
      of DNA DSBs would be incompatible with cell proliferation. Yet recent
      experimental findings suggest that, in both precancerous lesions and cancers,
      activated oncogenes induce stalling and collapse of DNA replication forks, which
      in turn leads to formation of DNA DSBs. This continuous formation of DNA DSBs may
      contribute to the genomic instability that characterizes the vast majority of
      human cancers. In addition, in precancerous lesions, these DNA DSBs activate p53,
      which, by inducing apoptosis or senescence, raises a barrier to tumor
      progression. Breach of this barrier by various mechanisms, most notably by p53
      mutations, that impair the DNA damage response pathway allows cancers to develop.
      Thus, oncogene-induced DNA damage may explain two key features of cancer: genomic
      instability and the high frequency of p53 mutations.

PMID- 18323445
TI  - Dimethylsulfoniopropionate as a foraging cue for reef fishes.
AB  - Coral reefs resemble islands of productive habitats where fishes aggregate,
      forage, and spawn. Although it has been suggested that some reef fishes use
      biogenic chemicals as aggregation cues, specific chemicals have not been
      identified. Dimethylsulfoniopropionate (DMSP), a secondary metabolite of many
      marine algal species, is released during foraging by higher-order consumers. DMSP
      has been studied intensively for its role in oceanic sulfur cycles and global
      climate regulation, but its ecological importance to marine fishes is unknown. We
      present evidence that planktivorous reef fishes will aggregate to experimental
      deployments of DMSP over coral reef habitats in the wild.

PMID- 18323446
TI  - Long-term sea-level fluctuations driven by ocean basin dynamics.
AB  - Earth's long-term sea-level history is characterized by widespread continental
      flooding in the Cretaceous period (approximately 145 to 65 million years ago),
      followed by gradual regression of inland seas. However, published estimates of
      the Late Cretaceous sea-level high differ by half an order of magnitude, from
      approximately 40 to approximately 250 meters above the present level. The low
      estimate is based on the stratigraphy of the New Jersey margin. By assimilating
      marine geophysical data into reconstructions of ancient ocean basins, we model a
      Late Cretaceous sea level that is 170 (85 to 270) meters higher than it is today.
      We use a mantle convection model to suggest that New Jersey subsided by 105 to
      180 meters in the past 70 million years because of North America's westward
      passage over the subducted Farallon plate. This mechanism reconciles New Jersey
      margin-based sea-level estimates with ocean basin reconstructions.

PMID- 18323447
TI  - Antisocial punishment across societies.
AB  - We document the widespread existence of antisocial punishment, that is, the
      sanctioning of people who behave prosocially. Our evidence comes from public
      goods experiments that we conducted in 16 comparable participant pools around the
      world. However, there is a huge cross-societal variation. Some participant pools
      punished the high contributors as much as they punished the low contributors,
      whereas in others people only punished low contributors. In some participant
      pools, antisocial punishment was strong enough to remove the cooperation
      enhancing effect of punishment. We also show that weak norms of civic cooperation
      and the weakness of the rule of law in a country are significant predictors of
      antisocial punishment. Our results show that punishment opportunities are
      socially beneficial only if complemented by strong social norms of cooperation.

PMID- 18323448
TI  - Fiber-optical analog of the event horizon.
AB  - The physics at the event horizon resembles the behavior of waves in moving media.
      Horizons are formed where the local speed of the medium exceeds the wave
      velocity. We used ultrashort pulses in microstructured optical fibers to
      demonstrate the formation of an artificial event horizon in optics. We observed a
      classical optical effect: the blue-shifting of light at a white-hole horizon. We
      also showed by theoretical calculations that such a system is capable of probing
      the quantum effects of horizons, in particular Hawking radiation.

PMID- 18323449
TI  - Stimuli-responsive polymer nanocomposites inspired by the sea cucumber dermis.
AB  - Sea cucumbers, like other echinoderms, have the ability to rapidly and reversibly
      alter the stiffness of their inner dermis. It has been proposed that the modulus
      of this tissue is controlled by regulating the interactions among collagen
      fibrils, which reinforce a low-modulus matrix. We report on a family of polymer
      nanocomposites, which mimic this architecture and display similar chemoresponsive
      mechanic adaptability. Materials based on a rubbery host polymer and rigid
      cellulose nanofibers exhibit a reversible reduction by a factor of 40 of the
      tensile modulus, for example, from 800 to 20 megapascals (MPa), upon exposure to
      a chemical regulator that mediates nanofiber interactions. Using a host polymer
      with a thermal transition in the regime of interest, we demonstrated even larger
      modulus changes (4200 to 1.6 MPa) upon exposure to emulated physiological
      conditions.

PMID- 18323450
TI  - Heterogeneous nucleation experiments bridging the scale from molecular ion
      clusters to nanoparticles.
AB  - Generation, investigation, and manipulation of nanostructured materials are of
      fundamental and practical importance for several disciplines, including materials
      science and medicine. Recently, atmospheric new particle formation in the
      nanometer-size range has been found to be a global phenomenon. Still, its
      detailed mechanisms are mostly unknown, largely depending on the incapability to
      generate and measure nanoparticles in a controlled way. In our experiments, an
      organic vapor (n-propanol) condenses on molecular ions, as well as on charged and
      uncharged inorganic nanoparticles, via initial activation by heterogeneous
      nucleation. We found a smooth transition in activation behavior as a function of
      size and activation to occur well before the onset of homogeneous nucleation.
      Furthermore, nucleation enhancement for charged particles and a substantial
      negative sign preference were quantitatively detected.

PMID- 18323451
TI  - Age and evolution of the Grand Canyon revealed by U-Pb dating of water table-type
      speleothems.
AB  - The age and evolution of the Grand Canyon have been subjects of great interest
      and debate since its discovery. We found that cave mammillaries (water table
      indicator speleothems) from nine sites in the Grand Canyon showed uranium-lead
      dating evidence for an old western Grand Canyon on the assumption that
      groundwater table decline rates are equivalent to incision rates. Samples in the
      western Grand Canyon yielded apparent water table decline rates of 55 to 123
      meters per million years over the past 17 million years, in contrast to eastern
      Grand Canyon samples that yielded much faster rates (166 to 411 meters per
      million years). Chronology and inferred incision data indicate that the Grand
      Canyon evolved via headward erosion from west to east, together with late-stage (
      approximately 3.7 million years ago) accelerated incision in the eastern block.

PMID- 18323452
TI  - The dust halo of Saturn's largest icy moon, Rhea.
AB  - Saturn's moon Rhea had been considered massive enough to retain a thin,
      externally generated atmosphere capable of locally affecting Saturn's
      magnetosphere. The Cassini spacecraft's in situ observations reveal that
      energetic electrons are depleted in the moon's vicinity. The absence of a
      substantial exosphere implies that Rhea's magnetospheric interaction region,
      rather than being exclusively induced by sputtered gas and its products, likely
      contains solid material that can absorb magnetospheric particles. Combined
      observations from several instruments suggest that this material is in the form
      of grains and boulders up to several decimetres in size and orbits Rhea as an
      equatorial debris disk. Within this disk may reside denser, discrete rings or
      arcs of material.

PMID- 18323453
TI  - De novo computational design of retro-aldol enzymes.
AB  - The creation of enzymes capable of catalyzing any desired chemical reaction is a
      grand challenge for computational protein design. Using new algorithms that rely
      on hashing techniques to construct active sites for multistep reactions, we
      designed retro-aldolases that use four different catalytic motifs to catalyze the
      breaking of a carbon-carbon bond in a nonnatural substrate. Of the 72 designs
      that were experimentally characterized, 32, spanning a range of protein folds,
      had detectable retro-aldolase activity. Designs that used an explicit water
      molecule to mediate proton shuffling were significantly more successful, with
      rate accelerations of up to four orders of magnitude and multiple turnovers, than
      those involving charged side-chain networks. The atomic accuracy of the design
      process was confirmed by the x-ray crystal structure of active designs embedded
      in two protein scaffolds, both of which were nearly superimposable on the design
      model.

PMID- 18323454
TI  - Hepatic glucose sensing via the CREB coactivator CRTC2.
AB  - Chronic hyperglycemia contributes to the development of diabetes-associated
      complications. Increases in the concentration of circulating glucose activate the
      hexosamine biosynthetic pathway (HBP) and promote the O-glycosylation of proteins
      by O-glycosyl transferase (OGT). We show that OGT triggered hepatic
      gluconeogenesis through the O-glycosylation of the transducer of regulated cyclic
      adenosine monophosphate response element-binding protein (CREB) 2 (TORC2 or
      CRTC2). CRTC2 was O-glycosylated at sites that normally sequester CRTC2 in the
      cytoplasm through a phosphorylation-dependent mechanism. Decreasing amounts of O
      glycosylated CRTC2 by expression of the deglycosylating enzyme O-GlcNAcase
      blocked effects of glucose on gluconeogenesis, demonstrating the importance of
      the HBP in the development of glucose intolerance.

PMID- 18323455
TI  - Coiled-coil irregularities and instabilities in group A Streptococcus M1 are
      required for virulence.
AB  - Antigenically variable M proteins are major virulence factors and immunogens of
      the human pathogen group A Streptococcus (GAS). Here, we report the approximately
      3 angstrom resolution structure of a GAS M1 fragment containing the regions
      responsible for eliciting type-specific, protective immunity and for binding
      fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The
      structure revealed substantial irregularities and instabilities throughout the
      coiled coil of the M1 fragment. Similar structural irregularities occur in myosin
      and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune
      sequelae of GAS infection. Sequence idealization of a large segment of the M1
      coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory
      effects, and antibody cross-reactivity, whereas it left protective immunogenicity
      undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

PMID- 18323456
TI  - Synthesis and characterization of 125I-alpha-conotoxin ArIB[V11L;V16A], a
      selective alpha7 nicotinic acetylcholine receptor antagonist.
AB  - The alpha7 nicotinic acetylcholine receptors (nAChRs) are widely expressed both
      in the central nervous system (CNS) and periphery. In the CNS, 125I-alpha
      bungarotoxin is commonly used to identify alpha7 nAChRs specifically. However,
      alpha-bungarotoxin also interacts potently with alpha1* and alpha9alpha10 nAChRs,
      two receptor subtypes in peripheral tissues that are colocalized with the alpha7
      subtype. [3H]Methyllycaconitine is also frequently used as an alpha7-selective
      antagonist, but it has significant affinity for alpha6* and alpha9alpha10 nAChR
      subtypes. In this study, we have developed a highly alpha7-selective alpha
      conotoxin radioligand by iodination of a naturally occurring histidine. Both mono
      and diiodo derivatives were generated and purified (specific activities were
      2200 and 4400 Ci mmol(-1), respectively). The properties of the mono- and diiodo
      derivatives were very similar to each other, but the diiodo was less stable. For
      monoidodo peptide, saturation binding to mouse hippocampal membranes demonstrated
      a K(d) value of 1.15 +/- 0.13 nM, similar to that of 125I-alpha-bungarotoxin in
      the same preparations (0.52 +/- 0.16 nM). Association and dissociation kinetics
      were relatively rapid (k(obs) for association at 1 nM was 0.027 +/- 0.007 min(
      1); k(off) = 0.020 +/- 0.001 min(-1)). Selectivity was confirmed with
      autoradiography using alpha7-null mutant tissue: specific binding was abolished
      in all regions of alpha7(-/-) brains, whereas wild-type mice expressed high
      levels of labeling and low nonspecific binding. 125I-alpha-conotoxin ArIB[V11L;
      V16A] should prove useful where alpha7 nAChRs are coexpressed with other subtypes
      that are also labeled by existing ligands. Furthermore, true equilibrium binding
      experiments could be performed on alpha7 nAChRs, something that is impossible
      with 125I-alpha-bungarotoxin.

PMID- 18323457
TI  - MSFTZ, a flavanone derivative, induces human hepatoma cell apoptosis via a
      reactive oxygen species- and caspase-dependent mitochondrial pathway.
AB  - Hepatocellular carcinoma (HCC) is the most common malignancy of the liver. It is
      unfortunate that HCCs are highly refractory to conventional chemotherapy,
      radiation therapy, and even immunotherapy. Thus, novel therapeutic targets need
      to be sought for the successful treatment of HCCs. We now report that (+/-)
      (3aRS,4SR)-2-(2-chloro-4-methylsulfonylphenyl)-4'-chloro-3alpha,4-diethoxy
      flavane[4,3-d]-D1,9b-1,2,3-thiadiazoline (MSFTZ), a synthesized flavanone
      derivative, induced growth arrest and apoptosis of HCCs both in vitro and in
      vivo. MSFTZ induced a time- and dose-dependent increase in HCC apoptosis through
      caspase-3 activation and poly(ADP-ribose) polymerase-1 cleavage. Activation of
      caspase-9 induced by MSFTZ suggested that MSFTZ-induced signaling was mediated
      through a mitochondrial death pathway. In addition, we observed an elevation of
      reactive oxygen species (ROS) and a consequent loss of mitochondrial membrane
      potential, further suggesting that MSFTZ-induced death signaling was mediated
      through a mitochondrial oxygen stress pathway. These events were associated with
      a decrease and increase in Bcl-2 and Bax expression, respectively, as well as
      phosphorylation of mitogen-activated protein kinase (MAPK) and activation of p53
      MDM2 pathway. However, the antioxidant N-acetylcysteine opposed MSFTZ-mediated
      mitochondrial dysfunction, caspase activation, Bcl-2/Bax modulation, and
      apoptosis, supporting the role of ROS in the apoptotic process. We were surprised
      that we failed to observe the protective effect of N-acetylcysteine against MSFTZ
      induced MAPK activation. Furthermore, MSFTZ had an antitumor effect in vivo by
      34.8 to 78.7% reduction of tumor size in SMMC-7721-xenografted nude mice. We
      conclude that MSFTZ induces HCC cell apoptosis both in vivo and in vitro via
      caspase- and ROS-dependent mitochondrial pathway. In addition, MSFTZ has
      potential as a novel therapeutic agent for the treatment of HCC.

PMID- 18323458
TI  - PGC-1alpha: important for exercise performance?

PMID- 18323459
TI  - Assisting Mother Nature in postnatal chemoreceptor maturation.

PMID- 18323460
TI  - Impact of acute ascites on the action of the canine abdominal muscles.
AB  - Although ascites causes abdominal expansion, its effects on abdominal muscle
      function are uncertain. In the present study, progressively increasing ascites
      was induced in supine anesthetized dogs, and the changes in abdominal (DeltaPab)
      and airway opening (DeltaPao) pressure obtained during stimulation of the
      internal oblique and transversus abdominis muscles were measured; the changes in
      internal oblique muscle length were also measured. As ascites increased from 0 to
      100 ml/kg body wt, Pab and muscle length during relaxation increased. DeltaPab
      also showed a threefold increase (P < 0.001). However, DeltaPao decreased (P <
      0.001). When ascites increased further to 200 ml/kg, resting muscle length
      continued to increase and muscle shortening during stimulation became very small
      so that active muscle length was 155% of the resting muscle length in the control
      condition. Concomitantly, DeltaPab returned to the control value, and DeltaPao
      continued to decrease. Similar results were obtained with the animals in the head
      up posture, although the decrease in DeltaPao appeared only when ascites was
      greater than 125 ml/kg. It is concluded that 1) ascites adversely affects the
      expiratory action of the abdominal muscles on the lung; 2) this effect results
      primarily from the increase in diaphragm elastance; and 3) when ascites is
      severe, the abdomen cross-sectional area is also increased and the abdominal
      muscles are excessively lengthened so that their active pressure-generating
      ability itself is reduced.

PMID- 18323461
TI  - Scaling of myocardial mass to flow and morphometry of coronary arteries.
AB  - There is no doubt that scaling relations exist between myocardial mass and
      morphometry of coronary vasculature. The purpose of this study is to quantify
      several morphological (diameter, length, and volume) and functional (flow)
      parameters of the coronary arterial tree in relation to myocardial mass. Eight
      normal porcine hearts of 117-244 g (mean of 177.5 +/- 32.7) were used in this
      study. Various coronary subtrees of the left anterior descending, right coronary,
      and left circumflex arteries were perfused at pressure of 100 mmHg with different
      colors of a polymer (Microfil) to obtain rubber casts of arterial trees
      corresponding to different regions of myocardial mass. Volume, diameter, and
      cumulative length of coronary arteries were reconstructed from casts to analyze
      their relationship to the perfused myocardial mass. Volumetric flow was measured
      in relationship with perfused myocardial mass. Our results show that arterial
      volume is linearly related to regional myocardial mass, whereas the sum of
      coronary arterial branch lengths, vessel diameters, and volumetric flow show an
      approximately 3/4, 3/8, and 3/4 power-law relationship, respectively, in relation
      to myocardial mass. These scaling laws suggest fundamental design principles
      underlying the structure-function relationship of the coronary arterial tree that
      may facilitate diagnosis and management of diffuse coronary artery disease.

PMID- 18323463
TI  - Inhibition of CXCR2 attenuates bronchial angiogenesis in the ischemic rat lung.
AB  - Under conditions of chronic pulmonary ischemia, the bronchial circulation
      undergoes massive proliferation. However, little is known regarding the
      mechanisms that promote neovascularization. An expanding body of literature
      implicates the glutamic acid-leucine-arginine (ELR+) CXC chemokines and their G
      protein-coupled receptor, CXCR(2), as key proangiogenic components in the lung.
      We used a rat model of chronic pulmonary ischemia induced by left pulmonary
      artery ligation (LPAL) to study bronchial angiogenesis. Using a methacrylate
      mixture, we cast the systemic vasculature of the rat lung at weekly intervals
      after LPAL. Twenty-one days after LPAL, numerous large, tortuous bronchial
      arteries were observed surrounding the left main bronchus that penetrated the
      left lung parenchyma. In stark contrast, the right lung was essentially devoid of
      vessels. We quantified bronchial neovascularization using 15-microm radiolabeled
      microspheres to measure systemic blood flow to the left lung (n = 12 rats).
      Results showed that by 21 days after LPAL, bronchial blood flow to the ischemic
      left lung had increased >10-fold compared with controls 2 days after LPAL (P <
      0.01). Focusing on the predominant rat CXC chemokine that signals through
      CXCR(2), we measured increased levels of cytokine-induced neutrophil
      chemoattractant-3 protein expression in left lung homogenates early (4 and 24 h;
      n = 10 rats) after LPAL relative to paired right lung controls (P < 0.01).
      Treatment with a neutralizing antibody to CXCR(2) resulted in a significant
      decrease in neovascularization 21 days after LPAL (n = 9 rats; P < 0.01). Our
      results confirm the time course of bronchial angiogenesis in the rat and suggest
      the importance of CXC chemokines in promoting systemic neovascularization in the
      lung.

PMID- 18323462
TI  - Spatial and temporal heterogeneity of ventilator-associated lung injury after
      surfactant depletion.
AB  - Volutrauma and atelectrauma have been proposed as mechanisms of ventilator
      associated lung injury, but few studies have compared their relative importance
      in mediating lung injury. The objective of our study was to compare the injury
      produced by stretch (volutrauma) vs. cyclical recruitment (atelectrauma) after
      surfactant depletion. In saline-lavaged rabbits, we used high tidal volume, low
      respiratory rate, and low positive end-expiratory pressure to produce stretch
      injury in nondependent lung regions and cyclical recruitment in dependent lung
      regions. Tidal changes in shunt fraction were assessed by measuring arterial
      Po(2) oscillations. After ventilating for times ranging from 0 to 6 h, lungs were
      excised, sectioned gravitationally, and assessed for regional injury by
      evaluation of edema formation, chemokine expression, upregulation of inflammatory
      enzyme activity, and alveolar neutrophil accumulation. Edema formation, lung
      tissue interleukin-8 expression, and alveolar neutrophil accumulation progressed
      more rapidly in dependent lung regions, whereas macrophage chemotactic protein-1
      expression progressed more rapidly in nondependent lung regions. Temporal and
      regional heterogeneity of lung injury were substantial. In this surfactant
      depletion model of acute lung injury, cyclical recruitment produced more injury
      than stretch.

PMID- 18323464
TI  - Exercise and diet enhance fat oxidation and reduce insulin resistance in older
      obese adults.
AB  - Older, obese, and sedentary individuals are at high risk of developing diabetes
      and cardiovascular disease. Exercise training improves metabolic anomalies
      associated with such diseases, but the effects of caloric restriction in addition
      to exercise in such a high-risk group are not known. Changes in body composition
      and metabolism during a lifestyle intervention were investigated in 23 older,
      obese men and women (aged 66 +/- 1 yr, body mass index 33.2 +/- 1.4 kg/m(2)) with
      impaired glucose tolerance. All volunteers undertook 12 wk of aerobic exercise
      training [5 days/wk for 60 min at 75% maximal oxygen consumption (Vo(2max))] with
      either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or
      a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as
      dictated by nutritional counseling. Body composition (decreased fat mass;
      maintained fat-free mass), aerobic fitness (Vo(2max)), leptinemia, insulin
      sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle
      improved in both groups (P < 0.05). Improvements in body composition, leptin, and
      basal fat oxidation were greater in the hypocaloric group. Following the
      intervention, there was a correlation between the increase in basal fat oxidation
      and the decrease in IMCL (r = -0.53, P = 0.04). In addition, basal fat oxidation
      was associated with circulating leptin after (r = 0.65, P = 0.0007) but not
      before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that
      exercise training improves resting substrate oxidation and creates a metabolic
      milieu that appears to promote lipid utilization in skeletal muscle, thus
      facilitating a reversal of insulin resistance. We also demonstrate that leptin
      sensitivity is improved but that such a trend may rely on reducing caloric intake
      in addition to exercise training.

PMID- 18323465
TI  - Effect of expiratory muscle fatigue on exercise tolerance and locomotor muscle
      fatigue in healthy humans.
AB  - High-intensity exercise (> or =90% of maximal O(2) uptake) sustained to the limit
      of tolerance elicits expiratory muscle fatigue (EMF). We asked whether prior EMF
      affects subsequent exercise tolerance. Eight male subjects (means +/- SD; maximal
      O(2) uptake = 53.5 +/- 5.2 ml.kg(-1).min(-1)) cycled at 90% of peak power output
      to the limit of tolerance with (EMF-EX) and without (CON-EX) prior induction of
      EMF and for a time equal to that achieved in EMF-EX but without prior induction
      of EMF (ISO-EX). To induce EMF, subjects breathed against an expiratory flow
      resistor until task failure (15 breaths/min, 0.7 expiratory duty cycle, 40% of
      maximal expiratory gastric pressure). Fatigue of abdominal and quadriceps muscles
      was assessed by measuring the reduction relative to prior baseline values in
      magnetically evoked gastric twitch pressure (Pga(tw)) and quadriceps twitch force
      (Q(tw)), respectively. The reduction in Pga(tw) was not different after resistive
      breathing vs. after CON-EX (-27 +/- 5 vs. -26 +/- 6%; P = 0.127). Exercise time
      was reduced by 33 +/- 10% in EMF-EX vs. CON-EX (6.85 +/- 2.88 vs. 9.90 +/- 2.94
      min; P < 0.001). Exercise-induced abdominal and quadriceps muscle fatigue was
      greater after EMF-EX than after ISO-EX (-28 +/- 9 vs. -12 +/- 5% for Pga(tw), P =
      0.001; -28 +/- 7 vs. -14 +/- 6% for Q(tw), P = 0.015). Perceptual ratings of
      dyspnea and leg discomfort (Borg CR10) were higher at 1 and 3 min and at end
      exercise during EMF-EX vs. during ISO-EX (P < 0.05). Percent changes in limb
      fatigue and leg discomfort (EMF-EX vs. ISO-EX) correlated significantly with the
      change in exercise time. We propose that EMF impaired subsequent exercise
      tolerance primarily through an increased severity of limb locomotor muscle
      fatigue and a heightened perception of leg discomfort.

PMID- 18323466
TI  - Diet-induced obesity causes innate airway hyperresponsiveness to methacholine and
      enhances ozone-induced pulmonary inflammation.
AB  - We previously reported that genetically obese mice exhibit innate airway
      hyperresponsiveness (AHR) and enhanced ozone (O(3))-induced pulmonary
      inflammation. Such genetic deficiencies in mice are rare in humans, and they may
      not be representative of human obesity. Thus the purpose of this study was to
      determine the pulmonary phenotype of mice with diet-induced obesity (DIO), which
      more closely mimics the cause of human obesity. Therefore, wild-type C57BL/6 mice
      were reared from the time of weaning until at least 30 wk of age on diets in
      which either 10 or 60% of the calories are derived from fat in the form of lard.
      Body mass was approximately 40% greater in mice fed 60 vs. 10% fat diets.
      Baseline airway responsiveness to intravenous methacholine, measured by forced
      oscillation, was greater in mice fed 60 vs. 10% fat diets. We also examined lung
      permeability and inflammation after exposure to room air or O(3) (2 parts/million
      for 3 h), an asthma trigger. Four hours after the exposure ended, O(3)-induced
      increases in bronchoalveolar lavage fluid protein, interleukin-6, KC, macrophage
      inflammatory protein-2, interferon-gamma-inducible protein-10, and eotaxin were
      greater in mice fed 60 vs. 10% fat diets. Innate AHR and augmented responses to
      O(3) were not observed in mice raised from weaning until 20-22 wk of age on a 60%
      fat diet. These results indicate that mice with DIO exhibit innate AHR and
      enhanced O(3)-induced pulmonary inflammation, similar to genetically obese mice.
      However, mice with DIO must remain obese for an extended period of time before
      this pulmonary phenotype is observed.

PMID- 18323467
TI  - Skeletal muscle protein anabolic response to resistance exercise and essential
      amino acids is delayed with aging.
AB  - Skeletal muscle loss during aging leads to an increased risk of falls, fractures,
      and eventually loss of independence. Resistance exercise is a useful intervention
      to prevent sarcopenia; however, the muscle protein synthesis (MPS) response to
      resistance exercise is less in elderly compared with young subjects. On the other
      hand, essential amino acids (EAA) increase MPS equally in both young and old
      subjects when sufficient EAA is ingested. We hypothesized that EAA ingestion
      following a bout of resistance exercise would stimulate anabolic signaling and
      MPS similarly between young and old men. Each subject ingested 20 g of EAA 1 h
      following leg resistance exercise. Muscle biopsies were obtained before and 1, 3,
      and 6 h after exercise to measure the rate of MPS and signaling pathways that
      regulate translation initiation. MPS increased early in young (1-3 h
      postexercise) and later in old (3-6 h postexercise). At 1 h postexercise, ERK1/2
      MNK1 phosphorylation increased and eIF2alpha phosphorylation decreased only in
      the young. mTOR signaling (mTOR, S6K1, 4E-BP1, eEF2) was similar between groups
      at all time points, but MNK1 phosphorylation was lower at 3 h and AMP-activated
      protein kinase-alpha (AMPKalpha) phosphorylation was higher in old 1-3 h
      postexercise. We conclude that the acute MPS response after resistance exercise
      and EAA ingestion is similar between young and old men; however, the response is
      delayed with aging. Unresponsive ERK1/2 signaling and AMPK activation in old
      muscle may be playing a role in the delayed activation of MPS. Notwithstanding,
      the combination of resistance exercise and EAA ingestion should be a useful
      strategy to combat sarcopenia.

PMID- 18323468
TI  - Endotoxin-induced proteolytic reduction in hepatic growth hormone (GH) receptor:
      a novel mechanism for GH insensitivity.
AB  - GH is an important anabolic hormone. We previously demonstrated in cell culture
      that the cell surface GH receptor (GHR) is susceptible to inducible
      metalloproteolytic cleavage that yields the shed receptor extracellular domain
      (called GH binding protein) and renders the cells desensitized to subsequent GH
      stimulation. Sepsis and inflammatory states are associated with hepatic
      desensitization to GH, although disparate mechanisms have been postulated in
      various animal models. Using C3H/HeJ mice, we now demonstrate that administration
      of lipopolysaccharide (LPS) causes marked hepatic desensitization to GH, assessed
      by monitoring signal transducer and activator of transcription 5 tyrosine
      phosphorylation and nuclear accumulation and with a novel noninvasive
      bioluminescence imaging system to track in vivo hepatic GH signaling serially in
      individual mice. This endotoxin-induced desensitization was accompanied by marked
      loss of hepatic GHR, which was not explained by changes in GHR mRNA abundance.
      Furthermore, we observe that LPS causes GH-binding protein shedding of a
      hepatically expressed wild-type GHR but not a GHR with a mutation in the
      metalloprotease cleavage site. These data suggest that in this model system, LPS
      induced desensitization to GH is associated with proteolytic GHR cleavage. These
      data are the first to demonstrate inducible in vivo GHR proteolysis and suggest
      this is a mechanism to regulate GH sensitivity and its anabolic effects during
      sepsis or inflammation.

PMID- 18323469
TI  - Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for
      feedback regulation of bile acid synthesis.
AB  - Liver receptor homolog 1 (LRH-1), an orphan nuclear receptor, is highly expressed
      in liver and intestine, where it is implicated in the regulation of cholesterol,
      bile acid, and steroid hormone homeostasis. Among the proposed LRH-1 target genes
      in liver are those encoding cholesterol 7alpha-hydroxylase (CYP7A1) and sterol
      12alpha-hydroxylase (CYP8B1), which catalyze key steps in bile acid synthesis. In
      vitro studies suggest that LRH-1 may be involved both in stimulating basal CYP7A1
      and CYP8B1 transcription and in repressing their expression as part of the
      nuclear bile acid receptor [farnesoid X receptor (FXR)]-small heterodimer partner
      signaling cascade, which culminates in small heterodimer partner binding to LRH-1
      to repress gene transcription. However, in vivo analysis of LRH-1 actions has
      been hampered by the embryonic lethality of Lrh-1 knockout mice. To overcome this
      obstacle, mice were generated in which Lrh-1 was selectively disrupted in either
      hepatocytes or intestinal epithelium. LRH-1 deficiency in either tissue changed
      mRNA levels of genes involved in cholesterol and bile acid homeostasis.
      Surprisingly, LRH-1 deficiency in hepatocytes had no significant effect on basal
      Cyp7a1 expression or its repression by FXR. Whereas Cyp8b1 repression by FXR was
      also intact in mice deficient for LRH-1 in hepatocytes, basal CYP8B1 mRNA levels
      were significantly decreased, and there were corresponding changes in the
      composition of the bile acid pool. Taken together, these data reveal a broad role
      for LRH-1 in regulating bile acid homeostasis but demonstrate that LRH-1 is
      either not involved in the feedback regulation of bile acid synthesis or is
      compensated for by other factors.

PMID- 18323470
TI  - Arginase I induction by modified lipoproteins in macrophages: a peroxisome
      proliferator-activated receptor-gamma/delta-mediated effect that links lipid
      metabolism and immunity.
AB  - Macrophages are phagocytic cells that play essential roles in innate immunity and
      lipid homeostasis. The uptake of modified lipoproteins is an important early
      event in the development of atherosclerosis. We analyzed the ability of modified
      low-density lipoprotein (LDL) (oxidized and acetylated) to alter the expression
      and activity of arginases (ArgI and ArgII) in macrophages. We show that ArgI
      expression is potently induced by both oxidized and acetylated LDL in
      macrophages. We further show that this effect is mediated by peroxisome
      proliferator-activated receptors (PPAR). ArgI expression is highly responsive to
      agonists for PPARgamma and PPARdelta but not PPARalpha. Moreover, the induction
      of ArgI by both PPAR agonists and IL-4 is blocked in macrophages from PPARgamma-
      and PPARdelta-deficient mice. Functionally, PPAR activity induces macrophage
      activation toward a more Th2 immune phenotype in a model of Leishmania major
      infection. We show that PPARgamma and -delta ligands promote intracellular
      amastigote growth in infected macrophages, and this effect is dependent on both
      PPAR expression and Arg activity. Collectively, our results strongly suggest that
      ArgI is a key marker of the alternative program triggered by PPAR in macrophages.

PMID- 18323471
TI  - Stroke in Korean.

PMID- 18323472
TI  - The ideal antiplatelet drug for stroke prevention--still elusive.

PMID- 18323473
TI  - Gender differences between high-sensitivity C-reactive protein and intima media
      thickness progression.

PMID- 18323474
TI  - Where do we go for atherothrombotic disease genetics?

PMID- 18323475
TI  - Metabolic syndrome is associated with silent ischemic brain lesions.
AB  - BACKGROUND AND PURPOSE: Metabolic syndrome (MetS) is a recognized risk factor for
      stroke, but it is unclear whether MetS is also related to subclinical ischemic
      lesions. We examined the association of MetS with the prevalence of silent brain
      infarction, periventricular hyperintensity, and subcortical white matter lesions
      in healthy adults. METHODS: We conducted a cross-sectional study in 1151 Japanese
      healthy subjects. Three types of silent lesions were assessed by MRI scans. MetS
      was diagnosed using the criteria by the National Cholesterol Education Adult
      Treatment Panel III. RESULTS: After adjusting for age and other factors, MetS was
      significantly associated with silent brain infarction, periventricular
      hyperintensity and subcortical white matter lesions. Among the MetS components,
      elevated blood pressure was commonly associated with all types of lesions.
      Dyslipidemia and elevated fasting glucose levels were associated with subcortical
      white matter lesions and periventricular hyperintensities, respectively. Positive
      trends were observed between the number of MetS components and prevalence of
      silent lesions. CONCLUSIONS: MetS is associated with the prevalence of silent
      lesions independent of other risk factors. The clustering of MetS components
      tends to increase the prevalence of silent lesions.

PMID- 18323476
TI  - Genetic variation of the androgen receptor and risk of myocardial infarction and
      ischemic stroke in women.
AB  - BACKGROUND AND PURPOSE: Androgen receptors (AR) are expressed in endothelial
      cells and vascular smooth-muscle cells. Some studies suggest an association
      between AR gene variation and risk of cardiovascular disease (CVD) in men;
      however, the relationship has not been examined in women. METHODS: Six haplotype
      block-tagging single nucleotide polymorphisms (rs962458, rs6152, rs1204038,
      rs2361634, rs1337080, rs1337082), as well as the cysteine, adenine, guanine (CAG)
      microsatellite in exon 1, of the AR gene were evaluated among 300 white
      postmenopausal women who developed CVD (158 myocardial infarctions and 142
      ischemic strokes) and an equal number of matched controls within the Women's
      Health Study. RESULTS: Genotype distributions were similar between cases and
      controls, and genotypes were not significantly related to risk of CVD, myocardial
      infarctions or ischemic stroke in conditional logistic regression models. Seven
      common haplotypes were observed, but distributions did not differ between cases
      and controls nor were significant associations observed in logistic regression
      analysis. The median CAG repeat length was 21. In conditional logistic
      regression, there was no association between the number of alleles with CAG
      repeat length >or=21 (or >or=22) and risk of CVD, myocardial infarctions or
      ischemic stroke. CONCLUSIONS: No association between AR genetic variation, as
      measured by haplotype-tagging single nucleotide polymorphisms and CAG repeat
      number, and risk of CVD was observed in women.

PMID- 18323477
TI  - The balance between stroke prevention and bleeding risk in atrial fibrillation: a
      delicate balance revisited.

PMID- 18323478
TI  - Intra-arterial thrombolysis of acute iatrogenic intracranial arterial occlusion
      attributable to neuroendovascular procedures or coronary angiography.
AB  - BACKGROUND AND PURPOSE: For selected stroke patients, intra-arterial thrombolysis
      (IAT) has been shown to be an effective treatment option. However, knowledge of
      safety and efficacy of IAT in patients with acute stroke as a complication of
      arterial catheter interventions is limited. METHODS: We analyzed clinical
      radiological findings and functional outcomes in consecutive patients 3 months
      after treatment with IAT for peri-procedural strokes occurring during
      neuroendovascular or cardiac catheter interventions. To measure outcome, the
      modified Rankin scale score was used. RESULTS: Of a total of 432 patients treated
      with IAT, 12 (4 women and 8 men; mean age, 60 years) were treated because of an
      ischemic stroke after a neuro-endovascular procedure (n=6) or coronary
      angiography (n=6). The median baseline National Institutes of Health Stroke Scale
      score was 15. Recanalization was complete (thrombolysis in myocardial infarction
      grade 3) in 6, partial (thrombolysis in myocardial infarction 2) in 5, and
      minimal (thrombolysis in myocardial infarction 1) in 1. Nine patients (75%) had a
      favorable outcome (modified Rankin scale score, 0 to 2), and 3 had a poor outcome
      (modified Rankin scale score, 3 or 4). All patients with complete recanalization
      had a favorable outcome, whereas only 3 of 6 patients with partial or minimal
      recanalization (P=0.18) had a favorable outcome. Follow-up brain imaging was
      normal in 2 and showed new ischemic lesions in 10 patients. Two patients (17%)
      had a symptomatic intracerebral hemorrhage. CONCLUSIONS: In acute stroke
      attributable to arterial catheter interventions, IAT is feasible and has the
      potential to improve outcome in these patients. A high recanalization rate could
      be achieved.

PMID- 18323479
TI  - Cerebrospinal fluid tenascin-C increases preceding the development of chronic
      shunt-dependent hydrocephalus after subarachnoid hemorrhage.
AB  - BACKGROUND AND PURPOSE: The possible cause of chronic hydrocephalus after
      subarachnoid hemorrhage (SAH) has been reported to be meningeal fibrosis. We
      examined whether the induction of tenascin-C (TN-C), an extracellular matrix
      glycoprotein known to promote tissue fibrosis, was associated with chronic
      hydrocephalus after SAH. METHODS: We prospectively measured cerebrospinal fluid
      TN-C levels in 7 control patients with unruptured cerebral aneurysms and in 29
      consecutive patients with aneurysmal SAH on days 1 to 12. RESULTS: Cerebrospinal
      fluid TN-C levels were less than the diagnostic threshold level in control
      patients but markedly increased after SAH. Higher TN-C levels were observed in
      patients with more severe SAH on admission CT, ventricular drainage for acute
      obstructive hydrocephalus, and a worse outcome. Independent of these factors,
      however, cerebrospinal fluid TN-C levels were significantly higher in patients
      with than without subsequent chronic shunt-dependent hydrocephalus on days 1 to
      9. CONCLUSIONS: These findings suggest the possible involvement of TN-C in the
      development of chronic hydrocephalus after SAH and encourage further studies.

PMID- 18323480
TI  - Cigarette smoking and risk of stroke in the chinese adult population.
AB  - BACKGROUND AND PURPOSE: We studied the relationship between cigarette smoking and
      stroke incidence and mortality in the Chinese adult population. METHODS: We
      conducted a prospective cohort study in a nationally representative sample of 169
      871 Chinese men and women aged 40 years and older. Data on cigarette smoking and
      other covariables were collected at a baseline examination in 1991 using a
      standard protocol. Follow-up evaluation was conducted in 1999 to 2000, with a
      response rate of 93.4%. RESULTS: During an average of 8.3 years follow-up, a
      total of 6780 stroke events (3979 fatal strokes) were observed. The multivariate
      adjusted relative risks (95% confidence interval) of stroke incidence and
      mortality associated with present cigarette smoking were 1.28 (1.19 to 1.37) and
      1.13 (1.03 to 1.25) in men and 1.25 (1.13 to 1.37) and 1.19 (1.04 to 1.36) in
      women, respectively. The corresponding population attributable risks were 14.2%
      and 7.1% in men and 3.1% and 2.4% in women. Compared to never-smokers, the
      multivariate-adjusted relative risks of stroke incidence (95% confidence
      interval) were 1.21 (1.12 to 1.31), 1.21 (1.11 to 1.32), and 1.36 (1.25 to 1.47)
      for those who smoked 1 to 9, 10 to 19, and >/=20 cigarettes per day; and 1.18
      (1.09 to 1.28), 1.25 (1.15 to 1.35), and 1.34 (1.24 to 1.44) for those who smoked
      1 to 11, 12 to 26, and >26 pack-years, respectively (both P<0.0001 for linear
      trends). CONCLUSIONS: Our study identified a positive and dose-response
      relationship between cigarette smoking and risk of stroke. Smoking prevention and
      cessation programs should be an important strategy for reducing the burden of
      stroke in Chinese adults.

PMID- 18323481
TI  - Staged escalation therapy in acute basilar artery occlusion: intravenous
      thrombolysis and on-demand consecutive endovascular mechanical thrombectomy:
      preliminary experience in 16 patients.
AB  - BACKGROUND AND PURPOSE: The prognosis of acute basilar artery occlusion (BAO) is
      poor if early recanalization is not achieved. Recanalization strategies include
      intravenous thrombolysis (IVT) and intra-arterial thrombolysis, as well as
      endovascular mechanical thrombectomy (EMT). The combination of IVT with
      consecutive on-demand EMT may allow for early treatment initiation with high
      recanalization rates but has never been systematically tested in patients with
      BAO. METHODS: Starting in January 2006, we treated all eligible patients with
      acute BAO admitted to our academic stroke center or one of our cooperating
      community hospitals after a standardized protocol combining IVT with consecutive
      on-demand EMT. Inclusion criteria were: (1) presence of predefined symptoms
      clearly suggestive of BAO; (2) exclusion of intracerebral hemorrhage on CT scan;
      (3) evidence of BAO on CT angiography; (4) start of therapy within 6 hours after
      symptom onset; and (5) no contraindications for IVT. If CT angiography showed
      persistent BAO after IVT, EMT was performed. RESULTS: Since January 2006, 16
      patients have been treated. All patients received IVT; in 7 of them, EMT became
      necessary because of persistent BAO. Final recanalization was achieved in 15
      patients. Three months after therapy, 12 of 16 patients were still alive; 7 of
      them had a good outcome (modified Rankin score <or=2). CONCLUSIONS: Our data
      suggest that the combination of IVT with on-demand consecutive EMT in BAO is
      feasible, allows for early treatment, and provides excellent recanalization
      rates.

PMID- 18323482
TI  - The metabolic syndrome: more than the sum of its components?

PMID- 18323483
TI  - Clinical and tissue response to intravenous thrombolysis in tandem internal
      carotid artery/middle cerebral artery occlusion: an MRI study.
AB  - BACKGROUND AND PURPOSE: The benefit of intravenous thrombolysis in tandem
      internal carotid artery (ICA)/middle cerebral artery (MCA) occlusion remains
      unclear. We studied clinical and imaging outcome of intravenous thrombolysis in
      MRI-selected patients with tandem ICA/MCA occlusion as compared to isolated MCA
      occlusion. METHODS: We analyzed data of MRI-selected acute ischemic stroke
      patients treated with intravenous tissue plasminogen activator within 6 hours.
      Initial perfusion and diffusion lesion volumes were calculated. Final infarct
      volume was assessed on follow-up imaging after 5 to 8 days.
      Recanalization/reperfusion was assessed after 24 hours using MRA. Favorable
      outcome was defined as a modified Rankin scale score of 0 to 1 after 90 days.
      RESULTS: Of 38 patients with proximal MCA occlusion, 14 (37%) had a tandem
      ICA/MCA occlusion. Median NIHSS on admission (15 vs 15), initial perfusion (246
      vs 246 mL), and diffusion lesion volume (22 vs 21 mL), final infarct volume (30
      vs 39 mL), and the proportion of patients with a favorable outcome after 3 months
      (50% vs 46%) were similar in tandem ICA/MCA occlusion versus isolated MCA
      occlusion. CONCLUSIONS: The presence of tissue at risk appears to play a key role
      for the likelihood of clinical recovery after intravenous tissue plasminogen
      activator treatment in acute stroke patients with tandem ICA/MCA occlusion. There
      appears to be no evidence to exclude patients with tandem ICA/MCA occlusion from
      intravenous thrombolysis.

PMID- 18323484
TI  - Predictors and outcomes of intraprocedural rupture in patients treated for
      ruptured intracranial aneurysms: the CARAT study.
AB  - BACKGROUND AND PURPOSE: Intraprocedural rupture (IPR) is a well known
      complication of intracranial aneurysm treatment. Risks and predictors of IPR and
      its impact on outcome have not been clearly established. METHODS: Potential
      predictors of IPR were evaluated in patients treated in the Cerebral Aneurysm
      Rerupture After Treatment (CARAT) study using multivariate logistic regression
      with stepwise elimination stratified by treatment modality. Periprocedural death
      or disability was defined as death or a change of >or=2 points on the Modified
      Rankin Scale at discharge compared to before treatment. RESULTS: IPR occurred in
      14.6% of 1010 patients (299 coiled, 711 clipped): 19% with clipping and 5% with
      coiling (P<0.001). Among those clipped, 31% with IPR had periprocedural death or
      disability compared to 18% without IPR (P=0.001); among those coiled, 63% with
      IPR had periprocedural death or disability compared to 15% without IPR (P<0.001).
      Overall, coronary artery disease and initial lower Hunt and Hess Grade were
      independent predictors of IPR. For those undergoing coiling, independent
      predictors of IPR were Asian race, black race, COPD, and lower initial Hunt and
      Hess Grade. Among those undergoing clipping, hyperlipidemia and lower initial
      Hunt and Hess Grade were both independent predictors of IPR. CONCLUSIONS: IPR was
      common in patients undergoing treatment of ruptured aneurysms, particularly with
      surgical clipping. The frequency of IPR with new disability was similar in the
      surgical and endovascular treatment groups. Coronary artery disease,
      hyperlipidemia, race, COPD, and lower Hunt and Hess Grade were associated with
      greater risk of IPR, which may reflect differences in vessel fragility but
      requires further confirmation.

PMID- 18323485
TI  - MRI detection of secondary damage after stroke: chronic iron accumulation in the
      thalamus of the rat brain.
AB  - BACKGROUND AND PURPOSE: Iron plays a central role in many metabolic processes.
      Under certain pathological situations it accumulates, producing negative effects
      such as increasing damage by oxidative stress. The present study examined long
      term iron accumulation in a stroke model with secondary degeneration, using MRI
      and histological techniques. METHODS: Male Wistar rats (n=22) were subjected to
      60 minutes MCA occlusion. MR images (T2- and T2*-weighted) were obtained weekly
      between weeks 1 and 7 after reperfusion, and at weeks 10, 14, 20, and 24.
      Histological iron detection and immunohistochemical examination for different
      markers (NeuN, GFAP, OX-42, HO-1, and APP) were performed at the 3 survival time
      points (3, 7, and 24 weeks). RESULTS: Infarcts affecting MCA territory were
      evident on T2-weighted imaging, and all animals showed deficits on behavioral
      tests. In the thalamus, T2 hyperintensity was detected 3 weeks after stroke, and
      disappeared around week 7 when T2*-weighted images showed a marked hypointensity
      in that area. Histology revealed neuronal loss in the thalamus, accompanied by
      strong microglial reactivity and microglial HO-1 expression. APP deposits were
      detected in the thalamus from week 3 on and persisted until week 24. Iron storage
      was detected in microglia at week 3, in the parenchyma at week 7, and around APP
      deposits at week 24. CONCLUSIONS: T2*-weighted MRI allows the detection of
      secondary damage in the thalamus after MCAO. Iron accumulation in the thalamus is
      mediated by HO-1 expression in reactive microglia.

PMID- 18323486
TI  - Stroke health and risk education (SHARE) pilot project: feasibility and need for
      church-based stroke health promotion in a bi-ethnic community.
AB  - BACKGROUND AND PURPOSE: We performed a pilot project to assess the need for and
      feasibility of a church-based stroke risk reduction intervention in a
      predominantly Mexican American community. METHODS: Participants were recruited
      after each mass on a single weekend from 2 Catholic churches in Corpus Christi,
      Texas. Questionnaires about personal stroke risk factors and interest in program
      participation were completed, and blood pressure screening was performed.
      RESULTS: A total of 150 individuals participated (63% Mexican American, median
      age 62). A substantial majority (84%) were interested in being part of a long
      term church-based health education project. Blood pressure was >139/89 mm Hg in
      50 of 78 (64%) of individuals with a self-reported history of hypertension, and
      in 17 of 69 (25%) of individuals without known hypertension, with no ethnic
      differences in blood pressure. Mexican Americans were younger, had a higher BMI,
      and were more likely to have diabetes than non-Hispanic whites. CONCLUSIONS:
      There is substantial burden of stroke risk factors in these predominantly Mexican
      American church communities. Church-based health interventions may be a way to
      reduce stroke in this at-risk population.

PMID- 18323487
TI  - Thunderclap headache: CT and lumbar puncture but occasionally more!

PMID- 18323488
TI  - Thunderclap headache with normal CT and lumbar puncture: further investigations
      are unnecessary: against.

PMID- 18323489
TI  - Thunderclap headache with normal CT and lumbar puncture: further investigations
      are unnecessary: for.

PMID- 18323490
TI  - Cerebral ischemic lesions on diffusion-weighted imaging are associated with
      neurocognitive decline after cardiac surgery.
AB  - BACKGROUND AND PURPOSE: Improvements in cardiac surgery mortality and morbidity
      have focused interest on the neurological injury such as stroke and cognitive
      decline that may accompany an otherwise successful operation. We aimed to
      investigate (1) the rate of stroke, new ischemic change on MRI, and cognitive
      impairment after cardiac valve surgery; and (2) the controversial relationship
      between perioperative cerebral ischemia and cognitive decline. METHODS: Forty
      patients (26 men; mean [SD] age 62.1 [13.7] years) undergoing intracardiac
      surgery (7 also with coronary artery bypass grafting) were studied. Neurological,
      neuropsychological, and MRI examinations were performed 24 hours before surgery
      and 5 days (MRI and neurology) and 6 weeks (neuropsychology and neurology) after
      surgery. Cognitive decline from baseline was determined using the Reliable Change
      Index. RESULTS: Two of 40 (5%) patients had perioperative strokes and 22 of 35
      (63%) tested had cognitive decline in at least one measure (range, 1 to 4).
      Sixteen of 37 participants (43%) with postoperative imaging had new ischemic
      lesions (range, 1 to 17 lesions) with appearances consistent with cerebral
      embolization. Cognitive decline was seen in all patients with, and 35% of those
      without, postoperative ischemic lesions (P<0.001), and there was an association
      between the number of abnormal cognitive tests and ischemic burden (P<0.001).
      CONCLUSIONS: We have provided a reliable estimate of the rate of stroke,
      postoperative ischemia, and cognitive impairment at 6 weeks after cardiac valve
      surgery. Cognitive impairment is associated with perioperative ischemia and is
      more severe with greater ischemic load.

PMID- 18323491
TI  - Genome screen to detect linkage to intracranial aneurysm susceptibility genes:
      the Familial Intracranial Aneurysm (FIA) study.
AB  - BACKGROUND AND PURPOSE: Evidence supports a substantial genetic contribution to
      the risk of intracranial aneurysm (IA). The purpose of this study was to identify
      chromosomal regions likely to harbor genes that contribute to the risk of IA.
      METHODS: Multiplex families having at least 2 individuals with "definite" or
      "probable" IA were ascertained through an international consortium. First-degree
      relatives of individuals with IA who were at increased risk of an IA because of a
      history of hypertension or present smoking were offered cerebral magnetic
      resonance angiography. A genome screen was completed using the Illumina 6K SNP
      system, and the resulting data from 192 families, containing 1155 genotyped
      individuals, were analyzed. Narrow and broad disease definitions were used when
      testing for linkage using multipoint model-independent methods. Ordered subset
      analysis was performed to test for a gene x smoking (pack-years) interaction.
      RESULTS: The greatest evidence of linkage was found on chromosomes 4 (LOD=2.5;
      156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using
      the broad disease definition. Using the average pack-years for the affected
      individuals in each family, the genes on chromosomes 4 (LOD=3.5; P=0.03), 7
      (LOD=4.1; P=0.01) and 12 (LOD=3.6; P=0.02) all appear to be modulated by the
      degree of smoking in the affected members of the family. On chromosome 8,
      inclusion of smoking as a covariate did not significantly strengthen the linkage
      evidence, suggesting no interaction between the loci in this region and smoking.
      CONCLUSIONS: We have detected possible evidence of linkage to 4 chromosomal
      regions. There is potential evidence for a gene x smoking interaction with 3 of
      the loci.

PMID- 18323492
TI  - Remodeling the brain: plastic structural brain changes produced by different
      motor therapies after stroke.
AB  - BACKGROUND AND PURPOSE: Studies on adult stroke patients have demonstrated
      functional changes in cortical excitability, metabolic rate, or blood flow after
      motor therapy, measures that can fluctuate rapidly over time. This study
      evaluated whether evidence could also be found for structural brain changes
      during an efficacious rehabilitation program. METHODS: Chronic stroke patients
      were randomly assigned to receive either constraint-induced movement therapy
      (n=16) or a comparison therapy (n=20). Longitudinal voxel-based morphometry was
      performed on structural MRI scans obtained immediately before and after patients
      received therapy. RESULTS: The group receiving constraint-induced movement
      therapy exhibited far greater improvement in use of the more affected arm in the
      life situation than the comparison therapy group. Structural brain changes
      paralleled these improvements in spontaneous use of the more impaired arm for
      activities of daily living. There were profuse increases in gray matter in
      sensory and motor areas both contralateral and ipsilateral to the affected arm
      that were bilaterally symmetrical, as well as bilaterally in the hippocampus. In
      contrast, the comparison therapy group failed to show gray matter increases.
      Importantly, the magnitude of the observed gray matter increases was
      significantly correlated with amount of improvement in real-world arm use.
      CONCLUSIONS: These findings suggest that a previously overlooked type of brain
      plasticity, structural remodeling of the human brain, is harnessed by constraint
      induced movement therapy for a condition once thought to be refractory to
      treatment: motor deficit in chronic stroke patients.

PMID- 18323493
TI  - Albumin therapy augments the effect of thrombolysis on local vascular dynamics in
      a rat model of arteriolar thrombosis: a two-photon laser-scanning microscopy
      study.
AB  - BACKGROUND AND PURPOSE: Results of our recent pilot clinical trial suggest that
      the efficacy of thrombolytic therapy in acute ischemic stroke may be enhanced by
      the coadministration of high-dose albumin. Here, we explored the microvascular
      hemodynamic effects of this combined therapy in a laboratory model of cortical
      arteriolar thrombosis. METHODS: We studied the cortical microcirculation of
      physiologically monitored rats in vivo by two-photon laser-scanning microscopy
      after plasma-labeling with fluorescein-dextran. We induced focal thrombosis in 30
      to 50-microm cortical arterioles by laser irradiation and measured arteriolar
      flow velocity by repeated line-scanning. At 30 minutes post-thrombosis, we
      treated animals with the thrombolytic agent, reteplase, which was coadministered
      with either human albumin, 2 g/kg, or with saline control. RESULTS: Baseline
      arteriolar flow velocity averaged 3.8+/-0.7 mm/s, was immediately reduced by
      thrombosis to 22% to 25% of control values, and remained unchanged before
      treatment. Subthrombolytic doses of reteplase combined with saline led to a
      median increase in flow velocity to 37% of control distal to the thrombus
      (P=nonsignificant versus pretreatment). By contrast, reteplase combined with
      albumin therapy resulted in a prompt, highly significant increase of median flow
      velocity to 58% of control levels (P=0.013 versus reteplase+saline), which
      remained significantly higher than the reteplase+saline group at multiple time
      points over the subsequent hour. CONCLUSIONS: The beneficial effect of
      subthrombolytic doses of reteplase on microvascular hemodynamics distal to a
      cortical arteriolar thrombosis is markedly enhanced by the coadministration of
      high-dose albumin therapy; these results have important clinical implications for
      the management of patients with acute ischemic stroke.

PMID- 18323494
TI  - Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with an
      increased risk of ischemic stroke in white Europeans.
AB  - BACKGROUND AND PURPOSE: Genetic variation in the EPHX2 gene region has been
      reported to influence susceptibility to ischemic stroke in blacks. We assessed
      the role of this gene region in white Europeans and performed analyses with
      regard to stroke subtypes. METHODS: Twenty-six single nucleotide polymorphisms in
      the EPHX2 gene region were genotyped in 601 patients with ischemic stroke and 736
      matched controls. Cases were subtyped according to the Trial of Org 10172 in
      Acute Stroke Treatment (TOAST) classification system. Analyses were done on
      single markers and haplotypes using a sliding-window approach. RESULTS: Three
      single nucleotide polymorphisms showed associations with an increased risk for
      ischemic stroke (allelic models; all P<or=0.01). One of them retained statistical
      significance after correction for multiple testing. Associations were observed
      with large-vessel stroke and stroke of undetermined etiology but not with other
      stroke subtypes. CONCLUSIONS: Our findings confirm and extend previous studies
      suggesting that genetic variation in or near the EPHX2 gene contributes to the
      risk of ischemic stroke. This association seems to be mediated predominantly by
      large-vessel disease.

PMID- 18323495
TI  - Dual-modality monitoring of targeted intraarterial delivery of mesenchymal stem
      cells after transient ischemia.
AB  - BACKGROUND AND PURPOSE: In animal models of stroke, functional improvement has
      been obtained after stem cell transplantation. Successful therapy depends largely
      on achieving a robust and targeted cell engraftment, with intraarterial (IA)
      injection being a potentially attractive route of administration. We assessed the
      suitability of laser Doppler flow (LDF) signal measurements and magnetic
      resonance (MR) imaging for noninvasive dual monitoring of targeted IA cell
      delivery. METHODS: Transient cerebral ischemia was induced in adult Wistar rats
      (n=25) followed by IA or intravenous (IV) injection of mesenchymal stem cells
      (MSCs) labeled with superparamagnetic iron oxide. Cell infusion was monitored in
      real time with transcranial laser Doppler flowmetry while cellular delivery was
      assessed with MRI in vivo (4.7 T) and ex vivo (9.4 T). RESULTS: Successful
      delivery of magnetically labeled MSCs could be readily visualized with MRI after
      IA but not IV injection. IA stem cell injection during acute stroke resulted in a
      high variability of cerebral engraftment. The amount of LDF reduction during cell
      infusion (up to 80%) was found to correlate well with the degree of intracerebral
      engraftment, with low LDF values being associated with significant morbidity.
      CONCLUSIONS: High cerebral engraftment rates are associated with impeded cerebral
      blood flow. Noninvasive dual-modality imaging enables monitoring of targeted cell
      delivery, and through interactive adjustment may improve the safety and efficacy
      of stem cell therapy.

PMID- 18323496
TI  - Induction of immunologic tolerance to myelin basic protein prevents central
      nervous system autoimmunity and improves outcome after stroke.
AB  - BACKGROUND AND PURPOSE: Animals subjected to an inflammatory insult at the time
      of stroke are predisposed to the development of an inflammatory autoimmune
      response to brain. This response is associated with worse neurological outcome.
      Because induction of immunologic tolerance to brain antigens before stroke onset
      is associated with improved outcome, we sought to determine whether this paradigm
      could prevent the deleterious autoimmune response to brain provoked by an
      inflammatory stimulus at the time of ischemia. METHODS: Male Lewis rats were
      tolerized to myelin basic protein (MBP) or ovalbumin by intranasal administration
      before middle cerebral artery occlusion. At the time of reperfusion, all animals
      received lipopolysaccharide (1 mg/kg intraperitoneal). Behavioral tests were
      performed at set time intervals. RESULTS: One month after middle cerebral artery
      occlusion, lymphocytes from the spleens of MBP-tolerized animals were less likely
      to evidence an autoimmune response and more likely to evidence a regulatory
      response (Treg) toward MBP than those from ovalbumin-tolerized animals. Animals
      that had an inflammatory response toward MBP (a Th1 response) performed worse on
      behavioral tests than those that did not. Fractalkine, a surrogate marker of
      inflammation, was elevated in animals with a Th1 response to MBP. CONCLUSIONS:
      These data extend our previous findings and suggest that deleterious autoimmunity
      to brain antigens can be prevented by prophylactically inducing regulatory T-cell
      responses to those antigens.

PMID- 18323497
TI  - Unrecognized myocardial infarction in relation to risk of dementia and cerebral
      small vessel disease.
AB  - BACKGROUND AND PURPOSE: Men, but not women, with unrecognized myocardial
      infarction (MI) have an increased risk of cardiac events and stroke compared with
      those without MI or with recognized MI. We investigated whether unrecognized MI
      is also a risk factor for dementia and cerebral small vessel disease (white
      matter lesions and brain infarction) in 2 population-based cohort studies.
      METHODS: In the Rotterdam Study, 6347 participants were classified at baseline
      (1990 to 1993) into those with recognized MI (subdivided into Q-wave and non-Q
      wave MI), with unrecognized MI, and without MI based on electrocardiography and
      interview and were followed for incident dementia (n=613) until January 1, 2005.
      In the Rotterdam Scan Study, 436 nondemented persons were similarly classified
      based on electrocardiography and interview and underwent brain MRI for the
      assessment of white matter lesions and brain infarction. RESULTS: In men,
      unrecognized MI was associated with an increased risk of dementia (compared with
      men without MI hazard ratio, 2.14; 95% CI, 1.37 to 3.35) and with more white
      matter lesions and more often brain infarction on MRI. In women, no associations
      were found with unrecognized MI. Recognized MI was not associated with the risk
      of dementia in either sex. Men, but not women, with recognized MI had more often
      any brain infarction or asymptomatic brain infarction, especially if they had Q
      wave MI. No consistent associations were found between recognized Q-wave or non-Q
      wave MI and severity of white matter lesions. Additional adjustment for
      cardiovascular risk factors did not change the results. CONCLUSIONS: Men with
      unrecognized MI have an increased risk of dementia and more cerebral small vessel
      disease.

PMID- 18323498
TI  - MMP-9-positive neutrophil infiltration is associated to blood-brain barrier
      breakdown and basal lamina type IV collagen degradation during hemorrhagic
      transformation after human ischemic stroke.
AB  - BACKGROUND AND PURPOSE: An abnormal expression of some matrix metalloproteinases
      (MMPs) is related with hemorrhagic transformation events after stroke. Our aim
      was to investigate MMP-2 and MMP-9 in the ischemic brain and its relation with
      blood-brain barrier breakdown after hemorrhagic transformation in human stroke.
      METHODS: We assessed 5 cases of fatal ischemic strokes with hemorrhagic
      complications; brain samples were obtained from infarct, hemorrhagic, and
      contralateral tissue. MMP-9 and MMP-2 content was analyzed by zymography and
      immunohistochemistry was performed to localize MMP-9 and to assess collagen IV
      integrity in the basal lamina. Laser capture microdissection was performed to
      isolate blood-brain barrier vessels to study these MMPs. RESULTS: Overall, MMP-9
      levels were higher both in hemorrhagic and nonhemorrhagic infarcted tissue
      compared to contralateral areas (P<0.0001 and P<0.05). Moreover, levels of the
      cleaved MMP-9 85kDa-form were significantly elevated in the hemorrhagic compared
      to nonhemorrhagic and contralateral areas (P=0.033 and P<0.0001). No changes were
      found for MMP-2 content. Immunostaining revealed a strong MMP-9-positive
      neutrophil infiltration surrounding brain microvessels associated with severe
      basal lamina type IV collagen degradation and blood extravasation.
      Microdissection confirmed that content of MMP-9 was similarly high in microvessel
      endothelium from hemorrhagic and infarcted areas compared to contralateral
      hemisphere vessels (P<0.05), pointing to neutrophils surrounding dissected
      microvessels as the main source of MMP-9 in hemorrhagic areas. CONCLUSIONS: Our
      results show a strong neutrophil infiltration in the infarcted and hemorrhagic
      areas with local high MMP-9 content closely related to basal lamina collagen IV
      degradation and blood-brain barrier breakdown. Microvessel and inflammatory MMP-9
      response are associated with hemorrhagic complications after stroke.

PMID- 18323500
TI  - Risks and benefits of oral anticoagulation compared with clopidogrel plus aspirin
      in patients with atrial fibrillation according to stroke risk: the atrial
      fibrillation clopidogrel trial with irbesartan for prevention of vascular events
      (ACTIVE-W).
AB  - BACKGROUND AND PURPOSE: In ACTIVE-W, oral anticoagulation (OAC) was more
      efficacious than combined clopidogrel plus aspirin (C+A) in preventing vascular
      events in patients with atrial fibrillation. However, because OAC carries
      important bleeding complications, risk stratification schemes have been devised
      to identify patients for whom the absolute benefits of OAC exceed its risks.
      METHODS: Participants were risk-stratified with the widely-used CHADS(2) scheme.
      Treatment-specific rates of stroke and major bleeding were calculated for
      patients with a CHADS(2)=1 and compared to those with a CHADS(2)>1. RESULTS:
      Observed stroke rates for those with a CHADS(2)=1 were 1.25% per year on C+A and
      0.43% per year on OAC (RR=2.96, 95% CI: 1.26 to 6.98, P=0.01). Among patients
      with a CHADS(2)>1, the stroke rates were 3.15% per year on C+A and 2.01% per year
      on OAC (RR=1.58, 95% CI: 1.11 to 2.24, P=0.01) (P for interaction between stroke
      risk category and efficacy of OAC=0.19). The risk of major bleeding during OAC
      was significantly lower among patients with CHADS(2)=1 (1.36% per year) compared
      with CHADS(2)>1 (2.75% per year) (RR=0.49, 95% CI 0.30 to 0.79, P=0.003).
      CONCLUSIONS: In this clinical trial, patients with a CHADS(2)=1 had a low risk of
      stroke, yet still derived a modest (<1% per year) but statistically significant
      absolute reduction in stroke with OAC and had low rates of major hemorrhage on
      OAC.

PMID- 18323501
TI  - The metabolic syndrome predicts incident stroke: a 14-year follow-up study in
      elderly people in Finland.
AB  - BACKGROUND AND PURPOSE: Limited information is available on the role of the
      metabolic syndrome (MetS) to predict stroke. We investigated the relationship of
      the MetS and its single components, defined by 6 different criteria, with stroke
      in a prospective population-based study. METHODS: The MetS was defined according
      to the World Health Organization, the European Group for the Study of Insulin
      Resistance, the National Cholesterol Education Program (NCEP), the American
      College of Endocrinology, the International Diabetes Federation, and the American
      Heart Association (updated NCEP) criteria. We investigated the relationship of
      the MetS with stroke using Cox regression analyses in 991 Finnish subjects
      without diabetes, aged 65 to 74 years at baseline, and followed-up for 14 years.
      RESULTS: The MetS defined by the World Health Organization, European Group for
      the Study of Insulin Resistance, NCEP, International Diabetes Federation, and
      updated NCEP criteria was significantly associated with incident stroke (fatal
      and nonfatal) when adjusted for confounding variables (HR, 1.52 to 1.72). After
      exclusion of subjects with myocardial infarction, these 5 definitions still
      predicted stroke (HR, 1.49 to 1.80). Of the single components of the MetS, the
      following predicted stroke in multivariable models when subjects with myocardial
      infarction were excluded: impaired glucose tolerance (2-hour glucose in an oral
      glucose tolerance test, 7.8 to 11.0 mmol/L) by the World Health Organization and
      American College of Endocrinology criteria (HR, 1.66); insulin resistance (HR,
      1.60) by the European Group for the Study of Insulin Resistance criteria; and
      central obesity (HR, 1.52) by the NCEP criteria. CONCLUSIONS: The MetS defined by
      the 6 criteria except for the American College of Endocrinology definition
      predicts stroke in elderly subjects. However, impaired glucose tolerance alone is
      as strong a predictor of stroke as is the MetS defined by the World Health
      Organization, NCEP and updated NCEP criteria.

PMID- 18323502
TI  - Applications and advantages of power motion-mode Doppler in acute posterior
      circulation cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Evaluation of posterior circulation with single-gate
      transcranial Doppler (TCD) is technically challenging and yields lower accuracy
      parameters in comparison to anterior circulation vessels. Transcranial power
      motion-mode Doppler (PMD-TCD), in addition to spectral information,
      simultaneously displays in real-time flow signal intensity and direction over 6
      cm of intracranial space. We aimed to evaluate the diagnostic accuracy of PMD-TCD
      against angiography in detection of acute posterior circulation stenoocclusive
      disease. METHODS: Consecutive patients presenting to the emergency room with
      symptoms of acute (<24 hours) cerebral ischemia underwent emergent neurovascular
      evaluation with PMD-TCD and angiography (computed tomographic angiography,
      magnetic resonance angiography, or digital subtraction angiography). Previously
      published diagnostic criteria were prospectively applied for PMD-TCD
      interpretation independent of angiographic findings. RESULTS: A total of 213
      patients (119 men; mean age 65+/-16 years; ischemic stroke 71%, transient
      ischemic attack 29%) underwent emergent neurovascular assessment. Compared with
      angiography, PMD-TCD showed 17 true-positive, 8 false-negative, 6 false-positive,
      and 182 true-negative studies in posterior circulation vessels (sensitivity 73%
      [55% to 91%], specificity 96% [93% to 99%], positive predictive value 68% [50% to
      86%], negative predictive value 95% [92% to 98%], accuracy 93% [90% to 96%]). In
      14 patients (82% of true-positive cases), PMD display showed diagnostic flow
      signatures complementary to the information provided by the spectral display:
      reverberating or alternating flow, distal basilar artery flow reversal, high
      resistance flow, emboli tracks and, bruit flow signatures. CONCLUSIONS: PMD-TCD
      yields a satisfactory agreement with urgent brain angiography in the evaluation
      of patients with acute posterior circulation cerebral ischemia. PMD display can
      depict flow signatures that are complimentary to and can increase confidence in
      standard single-gate TCD spectral findings.

PMID- 18323503
TI  - Simvastatin reduces the association of NMDA receptors to lipid rafts: a
      cholesterol-mediated effect in neuroprotection.
AB  - BACKGROUND AND PURPOSE: Excess brain extracellular glutamate induced by cerebral
      ischemia leads to neuronal death, mainly through overactivation of N-methyl-D
      aspartate (NMDA) receptors. The cholesterol-lowering drugs statins have been
      reported to protect from NMDA-induced neuronal death but, so far, the mechanism
      underlying this protection remains unclear. Because NMDA receptors have been
      reported to be associated with the cholesterol-rich membrane domains known as
      lipid rafts, we have investigated the effect of treatments that deplete
      cholesterol levels on excitotoxicity and on association of NMDA receptors to
      lipid rafts. METHODS: Primary neuronal cultures were pretreated with inhibitors
      of cholesterol synthesis and cholesterol, and NMDA-induced cell death was
      determined by measuring release of lactate dehydrogenase. Lipid raft fractions
      were isolated and Western blots were performed. RESULTS: Treatment with the
      inhibitors of cholesterol synthesis simvastatin, which inhibits the first step of
      cholesterol synthesis, or AY9944, which inhibits the last step of cholesterol
      synthesis, protected neurons from NMDA-induced neuronal death by 70% and 54%,
      respectively. Treatment with these compounds reduced neuronal cholesterol levels
      by 35% and 13%, respectively. Simvastatin and AY9944 reduced the association of
      the subunit 1 of NMDA receptors (NMDAR1) to lipid rafts by 42% and 21%,
      respectively, and did not change total expression of NMDAR1. Addition of
      cholesterol reduced neuroprotection by statins and AY9944, and partially reverted
      the effect of simvastatin on the association of NMDAR1 to lipid rafts.
      CONCLUSIONS: These data demonstrate that reduction of cholesterol levels protects
      from NMDA-induced neuronal damage probably by reducing the association of NMDA
      receptors to lipid rafts.

PMID- 18323504
TI  - Progression of symptomatic intracranial large artery atherosclerosis is
      associated with a proinflammatory state and impaired fibrinolysis.
AB  - BACKGROUND AND PURPOSE: The molecular pathways involved in the progression of
      intracranial large artery atherosclerosis (ILA) are largely unknown. Our
      objective was to prospectively study the relationship between circulating levels
      of inflammatory markers and fibrinolysis inhibitors, and the risk of progression
      of symptomatic ILA. METHODS: Seventy-five consecutive patients with first-ever
      symptomatic intracranial atherostenosis were studied. Blood levels of C-reactive
      protein (CRP), E-selectin, monocyte chemoattractant protein-1, intercellular
      adhesion molecule-1, matrix metalloproteinases 1, 2, 3, 8, 9, 10, and 13,
      plasminogen activator inhibitor-1 (PAI-1), and lipoprotein(a) were measured 3
      months after the qualifying stroke or transient ischemic attack. Thereafter,
      patients underwent long-term transcranial Doppler follow-up to detect progression
      of ILA. RESULTS: During a median follow-up time of 23 months, 25 (33%) patients
      showed ILA progression. Multivariable adjusted Cox regression models and Kaplan
      Meier curves showed that high baseline level of CRP, E-selectin, intercellular
      adhesion molecule-1, matrix metalloproteinase 9, PAI-1, and lipoprotein(a)
      predicted ILA progression independently of vascular risk factors. Of them, only
      CRP (CRP>5.5 mg/L; HR, 5.4 [2.3 to 12.7]; P=0.0001) and PAI-1 (PAI-1>23.1 ng/mL;
      HR, 2.4 [1.0 to 5.8]; P=0.05) predicted ILA progression also independently of the
      other studied molecules. CONCLUSIONS: Progression of symptomatic ILA is
      associated with a proinflammatory state, as reflected by high levels of
      inflammatory markers, and with defective fibrinolysis, as indicated by raised
      concentrations of endogenous fibrinolysis inhibitors.

PMID- 18323506
TI  - Rapid morphologic plasticity of peri-infarct dendritic spines after focal
      ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Focal stroke is associated with cell death, abnormal
      synaptic activity, and neurologic impairments. Given that many of these
      neuropathologic processes can be attributed to events that occur shortly after
      injury, it is necessary to understand how stroke affects the structure of neurons
      in surviving peri-infarct regions, particularly at the level of the dendritic
      spines, which transmit normal and potentially abnormal and injurious synaptic
      signaling. Recently, we described ischemia-induced changes in the structure of
      layer 1 dendritic tufts of transgenic mice expressing YFP in layer 5 cortical
      neurons. However, these in vivo imaging experiments could not address ischemia
      related phenomena that occur in deeper cortical structures/layers, other cortical
      regions, or submicron changes in dendritic spine structure. METHODS: Focal stroke
      was induced in the forelimb sensorimotor cortex by the photothrombotic method.
      Two, 6, and 24 hours after stroke, brains were processed for Golgi-Cox staining
      to permit a detailed analysis of primary apical dendritic spine structure from
      layer 2/3 and 5 cortical pyramidal neurons. RESULTS: Photothrombotic stroke
      caused a rapid deterioration of neurons, as revealed by Golgi-Cox labeling, in
      the infarct core that could be readily distinguished from surviving peri-infarct
      regions. Analysis of >15,000 dendritic spines revealed that although many spines
      were lost in the peri-infarct cortex during the first 24 hours after stroke
      (approximately 38% lost), spines that remained were significantly longer
      (approximately 25% at 6 hours). Furthermore, these effects were found in both
      layer 2/3 and 5 neurons and were restricted primarily to peri-infarct regions
      (<200 mum from the infarct border). CONCLUSIONS: These rapid changes in dendritic
      spine number and length may reflect an early adaptive response of potentially
      vulnerable peri-infarct neurons coping with postischemic spreading depression
      like depolarizations and the loss of presynaptic contacts.

PMID- 18323505
TI  - Progression of white matter hyperintensities and incidence of new lacunes over a
      3-year period: the Leukoaraiosis and Disability study.
AB  - BACKGROUND AND PURPOSE: We studied the natural course of white matter
      hyperintensities (WMH) and lacunes, the main MRI representatives of small vessel
      disease, over time and evaluated possible predictors for their development.
      METHODS: Baseline and repeat MRI (3-year follow-up) were collected within the
      multicenter, multinational Leukoaraiosis and Disability study (n=396). Baseline
      WMH were scored on MRI by the Fazekas scale and the Scheltens scale. WMH
      progression was assessed using the modified Rotterdam Progression scale
      (absence/presence of progression in 9 brain regions). Baseline and new lacunes
      were counted per region. WMH and lacunes at baseline and vascular risk factors
      were evaluated as predictors of WMH progression and new lacunes. RESULTS: WMH
      progressed (mean+/-SD=1.9+/-1.8) mostly in the subcortical white matter, where
      WMH was also most prevalent at baseline. The majority of new lacunes, which were
      found in 19% of the subjects (maximum=9), also appeared in the subcortical white
      matter, mainly of the frontal lobes, whereas most baseline lacunes were located
      in the basal ganglia. Baseline WMH and lacunes predicted both WMH progression and
      new lacunes. Furthermore, previous stroke, diabetes, and blood glucose were risk
      factors for WMH progression. Male sex, hypertension, systolic blood pressure,
      previous stroke, body mass index, high-density lipoprotein, and triglyceride
      levels were risk factors for new lacunes. CONCLUSIONS: WMH and lacunes progressed
      over time, predominantly in the subcortical white matter. Progression was
      observed especially in subjects with considerable WMH and lacunes at baseline.
      Moreover, the presence of vascular risk factors at baseline predicted WMH
      progression and new lacunes over a 3-year period.

PMID- 18323507
TI  - Misclassified tissue volumes in Alzheimer disease patients with white matter
      hyperintensities: importance of lesion segmentation procedures for volumetric
      analysis.
AB  - BACKGROUND AND PURPOSE: MRI-based quantification of gray and white matter volume
      is common in studies involving elderly patient populations. The aim of the
      present study was to describe the effects of not accounting for subcortical white
      matter hyperintensities (WMH) on tissue volumes in Alzheimer Disease patients
      with varying degrees of WMH (mild: n=19, moderate: n=22, severe: n=18). METHODS:
      An automated tissue segmentation protocol that was optimized for an elderly
      population, a brain regional parcellation procedure, and a lesion segmentation
      protocol were applied to measure tissue volumes (whole brain and regional lobar
      volumes) with and without lesion segmentation to quantify the volume of
      misclassified tissue. RESULTS: After application of the tissue segmentation
      protocol and lesion analysis, mean total percentage misclassified volume across
      all subjects was 2% (17.9 cm(3)) of whole brain volume (corrected for total
      intracranial capacity). Mean percentage of misclassified tissue volumes for the
      severe group was 4.8% of whole brain, which translates to a mean volume 42.2
      cm(3). Gray matter volume was most overestimated in the severe group, where 6.4%
      of the total gray matter volume was derived from misclassified WMH. The regional
      analysis showed that frontal (41%, 7.4 cm(3)) and inferior parietal (18%, 3.25
      cm(3)) lobes were most affected by tissue misclassification. CONCLUSIONS: MRI
      based volumetric studies of Alzheimer Disease that do not account for WMH can
      expect an erroneous inflation of gray or white matter volumes, especially in the
      frontal and inferior parietal regions. To avoid this source of error, MRI-based
      volumetric studies in patient populations susceptible to hyperintensities should
      include a WMH segmentation protocol.

PMID- 18323509
TI  - Trends in usage of alternative antiplatelet therapy after stroke and transient
      ischemic attack.
AB  - BACKGROUND AND PURPOSE: The effects of alternative antiplatelet agents such as
      clopidogrel and dipyridamole have been studied in clinical trials and heavily
      marketed. Because public data on their usage are limited, we examined trends in
      their prescription after stroke and transient ischemic attack to assess the
      impact of marketing and trial results. METHODS: Between 2001 and 2005, 85 US
      hospitals prospectively enrolled all patients admitted with ischemic stroke or
      transient ischemic attack into a registry designed for quality improvement
      (Ethos). Data on rates of antiplatelet medication usage at discharge were
      examined over time, and trends were evaluated by the Mantel-Haenszel test.
      RESULTS: Among 18 020 patients included during the 4-year period, 89% were
      discharged on antithrombotic medication. Between the first quarter of 2001 and
      the first quarter of 2004, prescription of clopidogrel-aspirin doubled (P<0.0001
      for trend), coincident with publication of results from CURE and CREDO showing
      efficacy in patients with acute coronary syndromes. Monotherapy with aspirin or
      clopidogrel decreased concomitantly, and use of dipyridamole-aspirin remained
      constant. After an increased bleeding risk was reported in the clopidogrel
      aspirin arm of the MATCH trial, use of the combination decreased sharply from
      31.5% in the first quarter of 2004 to 12.8% in the first quarter of 2005
      (P<0.0001), while an increase was seen in the use of clopidogrel alone (7.6% to
      12.8%, P=0.03) and dipyridamole-aspirin (7.4% to 20.2%, P<0.0001). CONCLUSIONS:
      Clopidogrel and dipyridamole-aspirin are used frequently after stroke or
      transient ischemic attack. Use of clopidogrel-aspirin was common in patients with
      recent ischemic stroke before the publication of MATCH, after which rates
      dramatically declined and use of dipyridamole-aspirin and clopidogrel alone
      increased.

PMID- 18323510
TI  - Benchmarks and determinants of adherence to stroke performance measures.
AB  - BACKGROUND AND PURPOSE: Develop achievable benchmarks for 9 stroke performance
      measures (PM) and to identify organizational factors associated with adherence.
      METHODS: Adherence rates and achievable benchmarks were determined for 9 PM
      within a study of patients (n=2294) admitted with acute ischemic stroke at 17
      hospitals. Baseline information regarding hospital characteristics and stroke
      specific processes of care were collected, and multi-level models were used to
      test the association of these factors with adherence. RESULTS: Benchmarks were
      >or=90% for 8 of the 9 PM. After controlling for clustering, only use of standing
      orders was associated with adherence to PM, including: dysphagia screening,
      venous thrombosis prophylaxis, consideration of tPA, and provision of educational
      material. CONCLUSIONS: High levels of adherence are achievable for several acute
      stroke PM. Use of standing orders is associated with adherence to PM requiring
      immediate action on admission.

PMID- 18323508
TI  - Cigarette smoking, systolic blood pressure, and cardiovascular diseases in the
      Asia-Pacific region.
AB  - BACKGROUND AND PURPOSE: Smoking and increased levels of blood pressure (BP)
      substantially increase the risk of cardiovascular diseases (CVD). If these 2 risk
      factors have a synergistic impact on cardiovascular events, lowering BP and
      quitting smoking will contribute more to reducing CVD than would be expected from
      ignoring their interaction. METHODS: Individual participant data were combined
      from 41 cohorts, involving 563 144 participants (82% Asian). During a median of
      6.8 years follow-up, 4344 coronary heart disease (CHD) and 5906 stroke events
      were recorded. Repeat measures of systolic blood pressure (SBP) were used to
      adjust for regression dilution bias. Hazard ratios (HRs) and 95% confidence
      intervals (CIs) for SBP by cigarette smoking status were estimated from Cox
      proportional hazard models adjusted for age and stratified by study and sex.
      RESULTS: Data suggested a log-linear relationship between SBP and all subtypes of
      CVD. The HRs relating SBP to both CHD and ischemic stroke were broadly similar
      irrespective of smoking status (P>/=0.1). For hemorrhagic stroke (intracerebral
      hemorrhage), the HRs (95% CIs) for an additional 10 mm Hg increment in SBP were
      1.81 (1.73 to 1.90) for present smokers and 1.66 (1.59 to 1.73) for nonsmokers
      (P=0.003). For every subtype of cardiovascular events, similar results were found
      for analyses involving only fatal events. CONCLUSIONS: Smoking exacerbated the
      impact of SBP on the risk of hemorrhagic stroke. Although quitting smoking and
      lowering BP are both crucial for prevention of CVD, combining the 2 could be
      expected to have extra beneficial effect on preventing hemorrhagic stroke.

PMID- 18323511
TI  - Aspirin plus dipyridamole versus aspirin for prevention of vascular events after
      stroke or TIA: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: This meta-analysis systematically reviewed randomized
      controlled trials comparing aspirin plus dipyridamole with aspirin alone in
      patients with stroke and TIA to determine the efficacy of these agents in
      preventing recurrent cerebral and systemic vascular events. METHODS: We performed
      separate analyses of the incidences of stroke alone and composite outcome of
      stroke, myocardial infarction, or vascular death. We also performed two subset
      analyses, planned a priori, to examine effect size based on trials using (1)
      exclusively immediate-release and (2) predominantly extended-release
      dipyridamole. RESULTS: The summary results indicate a significant reduction in
      the overall risk ratio in favor of aspirin plus dipyridamole for stroke alone
      with relative risk 0.77 (0.67 to 0.89) and the composite end point with relative
      risk 0.85 (0.76 to 0.94). Studies using immediate-release dipyridamole showed a
      nonstatistically significant trend in favor of the combination for stroke alone
      with relative risk 0.83 (0.59 to 1.15) and for the composite outcome with
      relative risk 0.95 (0.75 to 1.19). Studies using predominantly extended-release
      dipyridamole showed a statistically significant difference in favor of the
      combination for stroke alone with relative risk 0.76 (0.65 to 0.89) and for the
      composite outcome with relative risk 0.82 (0.73 to 0.92). CONCLUSIONS: The
      combination of aspirin plus dipyridamole is more effective than aspirin alone in
      preventing stroke and other serious vascular events in patients with minor stroke
      and TIAs. The risk reduction was greater and statistically significant for
      studies using primarily extended release dipyridamole, which may reflect a true
      pharmacological effect or lack of statistical power in studies using immediate
      release dipyridamole.

PMID- 18323512
TI  - Genetic variation in members of the leukotriene biosynthesis pathway confer an
      increased risk of ischemic stroke: a replication study in two independent
      populations.
AB  - BACKGROUND AND PURPOSE: The recent finding that genetic variants in 5
      lipoxygenase activating protein and leukotriene A4 hydrolase may confer an
      increased risk of ischemic stroke has implicated the leukotriene family as
      potential mediators of cardiovascular disease. Using a case control replication
      methodology, all members of the leukotriene synthesis pathway and their receptors
      were examined for genetic variants, which may act as risk factors for all
      ischemic stroke and stroke subtypes. METHODS: A case control methodology using a
      UK stroke cohort (872 cases, 933 controls) was adopted, with additional 5
      lipoxygenase activating protein genotyping and replication of positive findings
      undertaken in an independent stroke population from Germany (601 cases, 736
      controls). RESULTS: Association was identified with variants in 5-lipoxygenase
      activating protein, leukotriene C4 synthase (leukotriene A4 hydrolase),and the
      leukotriene B4 receptor complex. Differing risks were identified for ischemic
      stroke subtypes. A variant in leukotriene C4 synthase was found to confer a 1.5
      fold increase in risk of small vessel disease (RR, 1.515; 1.041 to 2.262;
      P=0.043) with replication in an independent cohort showing a similar risk (RR,
      1.687; 1.065 to 2.675; P=0.026). A haplotype in the leukotriene B4 receptor
      complex was found to confer a 2.3-fold increase in risk of cardioembolic stroke
      (RR, 2.118; 1.194 to 3.760; P=0.01) and replication in a German cohort revealed a
      similar risk with a second distinct haplotype (RR, 2.060; 1.162 to 3.665;
      P=0.013). CONCLUSIONS: Genetic variation in leukotriene pathway members and their
      receptors confer an increased risk of ischemic stroke in 2 independent
      populations. These risks show different magnitudes depending on ischemic stroke
      subtype.

PMID- 18323513
TI  - A whole-genome scan for stroke or myocardial infarction in family blood pressure
      program families.
AB  - BACKGROUND AND PURPOSE: Atherothrombotic diseases, including stroke and
      myocardial infarction, share a common pathogenesis. Chromosomal regions have been
      linked to atherothrombotic diseases in family studies, and association studies
      have identified candidate gene polymorphisms that affect the risk of stroke
      and/or myocardial infarction. Using data from the Family Blood Pressure Program,
      we tested for chromosomal regions linked to the composite phenotype of stroke or
      myocardial infarction in a large set of hypertensive families. METHODS:
      Nonparametric linkage analysis was implemented in MERLIN, which tests for excess
      allele-sharing among affected siblings. Empirical distributions based on gene
      dropping simulations were constructed for each test statistic, and the -log(10)
      of the associated probability values were compared. RESULTS: Analyses were based
      on 9607 individuals in 226 black, 395 Hispanic, and 207 white families; 106
      families had multiple affected individuals. Several regions showed linkage to
      stroke or myocardial infarction, most significantly in Hispanics on chromosomes
      2p21 (-log(10) P=3.0) and 7q21.1 (-log(10) P=2.8), 9q32 in blacks and Hispanics (
      log(10) P=3.0), 11p13 in blacks (-log(10) P=2.1), and 12q24.33 in whites (
      log(10) P=3.0). CONCLUSIONS: There is statistically significant evidence for loci
      affecting stroke or myocardial infarction on chromosomes 2, 9, and 12.

PMID- 18323514
TI  - Effects of statins on adipose tissue inflammation: their inhibitory effect on
      MyD88-independent IRF3/IFN-beta pathway in macrophages.
AB  - OBJECTIVE: Macrophage-mediated chronic inflammation of adipose tissue is causally
      linked to insulin resistance in obesity. The beneficial effects of 3-hydroxy-3
      methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors (statins) on glucose
      metabolism have been suggested, but the effects of these agents on adipose tissue
      inflammation are unclear. The aim of the present study is to define the effects
      of statins on adipose tissue inflammation and macrophages. METHODS AND RESULTS:
      Pravastatin or pitavastatin treatment of obese mice attenuated an increase in
      mRNA expressions of proinflammatory genes, including MCP1 and IL6, in adipose
      tissue. The supernatant of TLR4-stimulated RAW264 macrophages strongly induced
      the expression of these genes in 3T3-L1 adipocytes, which was inhibited by
      pretreatment of macrophages with either statin. Statins inhibited TLR4-mediated
      activation of interferon (IFN) regulatory factor (IRF)3 by either
      lipopolysaccharide (LPS) or palmitic acid, resulting in suppression of IFN-beta
      expression, but not that of NF-kappaB or JNK. Moreover, statins strongly
      downregulated TLR3-mediated gene expressions by poly(I:C), but not TLR2
      stimulation by zymosan A. Neutralization of IFN-beta attenuated proinflammatory
      activities of the macrophage supernatant. CONCLUSIONS: Statins partially
      attenuated the development of adipose tissue inflammation in obese mice, which
      might be associated with an inhibitory effect of statins on TLR4-triggered
      expression of IFN-beta via MyD88-independent signaling pathway in macrophages.

PMID- 18323515
TI  - Coffee consumption and coronary calcification: the Rotterdam Coronary
      Calcification Study.
AB  - BACKGROUND: The role of coffee in the cardiovascular system is not yet clear. We
      examined the relation of coffee intake with coronary calcification in a
      population-based cohort. METHODS AND RESULTS: The study involved 1570 older men
      and women without coronary heart disease who participated in the Rotterdam Study.
      Coffee intake was assessed with a semiquantitative food frequency questionnaire.
      Coronary calcification was detected with electron beam computed tomography.
      Severe calcification was defined as an Agatson calcium score >400. Sex-specific
      odds ratios (ORs) with 95% confidence intervals (95% CI) were obtained by
      logistic regression with adjustment for age, smoking, body mass index, education,
      and intake of energy and alcohol. In multivariable analysis, coronary
      calcification in women was significantly reduced for moderate (>3 to 4 cups) and
      high (>4 cups) coffee intake, compared with a daily intake of 3 cups or less (OR
      of 0.41 [95% CI: 0.25 to 0.65] and 0.54 [0.33 to 0.87], respectively). The
      association persisted after additional adjustment for tea and other dietary
      confounders, and was not modified by smoking. A nonsignificant inverse
      relationship was also found in men who smoked, whereas in nonsmoking men a direct
      association was observed. CONCLUSIONS: The present study suggests a beneficial
      effect of coffee drinking against coronary calcification, particularly in women.
      More research is needed to confirm these findings and to clarify possible effect
      modification by gender and smoking.

PMID- 18323516
TI  - Regulation of macrophage functions by PPAR-alpha, PPAR-gamma, and LXRs in mice
      and men.
AB  - Peroxisome proliferator-activated receptors (PPARs) and (liver X receptors) LXRs
      are ligand-activated transcription factors that control lipid and glucose
      metabolism, as well as the inflammatory response. Because the macrophage plays an
      important role in host defense and immunoinflammatory pathologies, particular
      attention has been paid to the role of PPARs and LXRs in the control of
      macrophage gene expression and function. Research over the last few years has
      revealed important roles for PPAR-alpha, PPAR-gamma, and LXRs in macrophage
      inflammation and cholesterol homeostasis with consequences for atherosclerosis
      development. In this review we will discuss the role of these transcription
      factors in the control of macrophage activities, with particular attention to
      species-differences in macrophage function control by PPARs and LXR between
      rodents and humans.

PMID- 18323517
TI  - Variants of the interferon regulatory factor 5 gene regulate expression of IRF5
      mRNA in atherosclerotic tissue but are not associated with myocardial infarction.
AB  - BACKGROUND: Signaling events after activation of toll-like receptors (TLRs) are
      important mechanisms promoting inflammation in the atherosclerotic plaque. INF
      regulatory factor 5 (IRF5) is one of the mediators of downstream effects of TLRs.
      Several single nucleotide polymorphisms (SNPs) in the IRF5 gene have been found
      to be associated with systemic lupus erythematosus. METHODS AND RESULTS: We
      examined IRF5 mRNA expression in carotid atherosclerotic tissue (n=99) and the
      case-control association between SNPs in the IRF5 gene with myocardial infarction
      (MI) (n=376+387) and unstable coronary artery disease (CAD) (n=3101+445). Among
      unstable CAD patients, association of IRF5 SNPs with recurrent coronary events
      (n=401) was also investigated. The IRF5 mRNA expression was increased in
      atherosclerotic tissue compared with control tissue (P<0.001). Significant
      associations with IRF5 expression was observed for 6 of 10 SNPs in the study.
      However, the IRF5 SNPs examined were neither associated with the risk of
      precocious MI, nor with unstable CAD or risk of recurrent cardiovascular events
      in unstable CAD patients. CONCLUSIONS: IRF5 mRNA is expressed in cells in
      atherosclerotic tissue and its expression is modified by SNPs in the IRF5 gene.
      Genetic variation at the IRF5 locus was, however, not associated with CAD or
      related phenotypes.

PMID- 18323518
TI  - Differential regulation of VEGF signaling by PKC-alpha and PKC-epsilon in
      endothelial cells.
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) stimulates proangiogenic
      signal transduction and cell function in part through activation of protein
      kinase C (PKC). Our aim was to examine how individual isoforms of PKC affect VEGF
      action. METHODS AND RESULTS: Transfection of bovine aortic endothelial cells with
      small interfering RNA (siRNA) targeting either PKC-alpha, delta, or epsilon
      caused a reduction in the cognate PKC protein by 76% to 89% without changing
      expression of nontargeted isoforms. Downregulation of PKC-epsilon abrogated VEGF
      stimulated phosphorylation of Akt at Ser473 and eNOS at Ser1179 and decreased
      VEGF-stimulated NO synthase activity in intact cells. In contrast, PKC-alpha
      knockdown increased Akt and eNOS phosphorylation, whereas PKCdelta knockdown had
      no significant effect. PKC-epsilon knockdown also decreased VEGF-stimulated
      Erk1/2 phosphorylation and abolished VEGF-stimulated DNA synthesis. Consistent
      with an effect on several pathways of VEGF signaling, VEGF receptor-2 (VEGFR2)
      tyrosine phosphorylation and expression of VEGFR2 protein and mRNA was decreased
      by 81, 90, and 84%, respectively, during knockdown of PKC-epsilon, but increased
      during PKC-alpha knockdown. CONCLUSIONS: By regulating VEGFR2 expression and
      activation, PKC-epsilon expression is critical for activation of Akt and eNOS by
      VEGF and contributes to VEGF-stimulated Erk activation, whereas PKC-alpha has
      opposite effects.

PMID- 18323519
TI  - Association of ANCA-positive vasculitis with thyroid disease.

PMID- 18323520
TI  - Screening for depression while patients dialyse: an evaluation.
AB  - BACKGROUND: The lack of routine depression screening among the haemodialysis (HD)
      population may contribute to depression being under-recognised. While screening
      patients could be beneficial, the optimum screening procedure remains unclear.
      One method would be to screen HD patients while they receive their treatment. The
      purpose of this investigation was to determine whether the Beck Depression
      Inventory-II (BDI) could be administered while patients dialysed. METHODS: Forty
      HD patients completed the BDI while dialysing and again at a time when off
      dialysis. Level of agreement analysis (Bland and Altman) was undertaken to
      determine if the assessment condition influenced BDI scoring. The off-dialysis
      assessment also involved a short clinical interview that was compared with the
      BDI assessment. RESULTS: There was a high level of agreement between the on- and
      off-dialysis assessments, but differences in response to the somatic items on the
      BDI scale were apparent between the conditions. The clinical interview revealed
      that 22% of the sample met the DSM-IV criteria for major depressive disorder. The
      optimal cut-off value for the BDI as determined by receiver operating
      characteristic curves was >or=16, with 88.9% sensitivity and 87.1% specificity.
      CONCLUSION: The results indicate that the procedure of on-dialysis assessment
      using the BDI is a viable screening procedure. The practicality of employing this
      screening procedure may facilitate improved detection of depression in the
      dialysis population.

PMID- 18323521
TI  - The impact of residual renal function on survival.

PMID- 18323522
TI  - Is it time to celebrate a century of blood pressure management?
AB  - BACKGROUND: Even after a century of hypertension management, several trivial
      issues have remained unsolved and still result in inadequate control of blood
      pressure in many patients. METHODS: We have performed a critical literature
      review on topics pertaining the assessment and management of hypertension,
      focusing on the gaps in knowledge and pitfalls of hypertension management in
      clinical practice. RESULTS: Physicians are often not capable of adequately
      measuring blood pressure themselves; the office blood pressure recordings are not
      sufficiently reliable and the timing of the start of the treatment is often not
      satisfactory. However, much progress has been made in the past century. Research
      in this field not only expanded the potential of blood pressure measurements for
      risk stratification and risk management but also identified many erroneous
      assumptions and technical mistakes. An important step forward may be the
      development of affordable 'high tech' blood pressure measuring devices that
      continuously monitor the intra-arterial pressure in a noninvasive way to
      eliminate human factors and equipment errors. Technological advances will also
      provide adequate data storage and software allowing management on an
      international scale. CONCLUSIONS: Hypertension management can almost be
      celebrated; however, the pressure is still on!

PMID- 18323523
TI  - Beneficial effect of the central nervous system beta-adrenoceptor blockade on the
      failing heart.
AB  - Heart failure patients are routinely given beta-adrenoceptor antagonists (beta
      blockers), although the mechanism(s) underlying their beneficial effects is not
      fully resolved. It is not entirely clear how long-term application of negative
      inotropic compounds improves cardiac performance, slows remodeling processes, and
      decreases mortality. All beta-blockers, which produce a beneficial effect in
      heart failure, have in common a high degree of lipophilicity and, therefore, have
      the ability to cross the blood-brain barrier. Here, we show that blockade of beta
      adrenoceptors directly in the brain (chronic intracerebroventricular
      administration of metoprolol) attenuates the progression of left ventricular
      remodeling in a rat model of myocardial infarction-induced heart failure. These
      results provide the first direct evidence that the action of certain beta
      blockers in the brain could contribute to their beneficial effect on the failing
      heart.

PMID- 18323524
TI  - Epac mediates beta-adrenergic receptor-induced cardiomyocyte hypertrophy.
AB  - Cardiac hypertrophy is promoted by adrenergic overactivation and can progress to
      heart failure, a leading cause of mortality worldwide. Although cAMP is among the
      most well-known signaling molecules produced by beta-adrenergic receptor
      stimulation, its mechanism of action in cardiac hypertrophy is not fully
      understood. The identification of Epac (exchange protein directly activated by
      cAMP) proteins as novel sensors for cAMP has broken the dogma surrounding cAMP
      and protein kinase A. However, their role and regulation in the mature heart
      remain to be defined. Here, we show that cardiac hypertrophy induced by thoracic
      aortic constriction increases Epac1 expression in rat myocardium. Adult
      ventricular myocytes isolated from banded animals display an exaggerated cellular
      growth in response to Epac activation. At the molecular level, Epac1 hypertrophic
      effects are independent of its classic effector, Rap1, but rather involve the
      small GTPase Ras, the phosphatase calcineurin, and Ca(2+)/calmodulin-dependent
      protein kinase II. Importantly, we find that in response to beta-adrenergic
      receptor stimulation, Epac1 activates Ras and induces adult cardiomyocyte
      hypertrophy in a cAMP-dependent but protein kinase A-independent manner.
      Knockdown of Epac1 strongly reduces beta-adrenergic receptor-induced hypertrophic
      program. Finally, we report for the first time that Epac1 is mainly expressed in
      human heart as compared with Epac2 isoform and is increased in heart failure.
      Taken together, our data demonstrate that the guanine nucleotide exchange factor
      Epac1 contributes to the hypertrophic effect of beta-adrenergic receptor in a
      protein kinase A-independent fashion and may, therefore, represent a novel
      therapeutic target for the treatment of cardiac disorders.

PMID- 18323525
TI  - Phosphatidylinositol-3-kinase-gamma is integral to homing functions of progenitor
      cells.
AB  - Endothelial progenitor cells (EPCs) and hematopoietic progenitor cells are
      recruited to ischemic regions, improving neovascularization. beta1 and beta2
      integrins play a crucial role for progenitor cell homing to ischemic tissues.
      Integrin activity is regulated by chemokines and their respective G protein
      coupled receptors. The phosphatidylinositol-3-kinase catalytic subunit gamma
      (PI3Kgamma) is the PI3K isoform that selectively transduces signals from G
      protein-coupled receptors. Here, we investigated the role of PI3Kgamma as a
      signaling intermediate in the chemokine-induced integrin-dependent homing
      functions of progenitor cells. A pharmacological PI3Kgamma inhibitor
      significantly reduced chemokine-induced chemotaxis and stromal cell-derived
      factor (SDF)1alpha-induced transmigration of human EPCs. Moreover, the PI3Kgamma
      inhibitor significantly reduced SDF1alpha-induced adhesion of EPCs to
      intercellular adhesion molecule-1 and human umbilical vein endothelial cell
      monolayers. These findings were corroborated with Lin(-) bone marrow-derived
      progenitor cells from PI3Kgamma-deficient mice that displayed reduced SDF1alpha
      induced migration and intercellular adhesion molecule-1 adhesion as compared with
      wild-type cells. Pharmacological inhibition or genetic ablation of PI3Kgamma
      reduced SDF1alpha-induced integrin activation in human EPCs and in murine Lin(-)
      BM-derived progenitor cells, respectively. In vivo, the homing of PI3Kgamma
      deficient Lin(-) progenitor cells to ischemic muscles after intravenous infusion
      in the model of hindlimb ischemia and their neovascularization-promoting capacity
      was reduced as compared with wild-type cells. In conclusion, PI3Kgamma is
      integral to the integrin-dependent homing of progenitor cells.

PMID- 18323526
TI  - Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages.
AB  - Activated macrophages acquire a proinflammatory (classic) or antiinflammatory
      (alternative) phenotype that influences atherosclerosis. The present study
      investigated whether sphingosine-1-phosphate (S1P), with its known
      antiinflammatory effects, could regulate the inflammatory phenotype of
      lipopolysaccharide (LPS)-stimulated mouse macrophages. Activation of macrophages
      by LPS significantly increases proinflammatory cytokine secretion. Pretreatment
      of macrophages with 500 nmol/L S1P markedly reduced LPS-mediated secretion of
      tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and interleukin
      12. Such antiinflammatory actions were also evident in LPS-stimulated macrophages
      treated with the S1P1 receptor-specific agonist SEW2871. Pharmacological
      antagonism of the S1P1 receptor on macrophages using the S1P1-specific antagonist
      VPC44116 also blocked proinflammatory cytokine secretion in response to LPS.
      Studies using bone marrow-derived macrophages from S1P2-deficient mice revealed
      that the S1P2 receptor did not play a pivotal role in this process. Thus,
      activation of the S1P1 receptor in mouse macrophages limits the expression of
      proinflammatory cytokines. Furthermore, we demonstrated that S1P increased
      arginase I activity and inhibited LPS-induced inducible NO synthase activity in
      LPS-treated macrophages, again through S1P1 receptor activation on macrophages.
      Analysis of a 1.7-kb region of the murine inducible NO synthase promoter revealed
      the presence of putative nuclear factor kappaB, activator protein-1, and STAT-1
      response elements. Using inducible NO synthase promoter-reporter constructs, we
      found that S1P significantly reduced the nuclear factor kappaB-mediated induction
      of inducible NO synthase. These findings demonstrate an important role for S1P in
      the regulation of macrophage phenotypic switching. Therefore, we conclude that
      S1P promotes the production of an alternative antiinflammatory macrophage
      phenotype through activation of the macrophage S1P1 receptor.

PMID- 18323527
TI  - Negative-feedback loop attenuates hydrostatic lung edema via a cGMP-dependent
      regulation of transient receptor potential vanilloid 4.
AB  - Although the formation of hydrostatic lung edema is generally attributed to
      imbalanced Starling forces, recent data show that lung endothelial cells respond
      to increased vascular pressure and may thus regulate vascular permeability and
      edema formation. In combining real-time optical imaging of the endothelial Ca(2+)
      concentration ([Ca(2+)](i)) and NO production with filtration coefficient (K(f))
      measurements in the isolated perfused lung, we identified a series of endothelial
      responses that constitute a negative-feedback loop to protect the microvascular
      barrier. Elevation of lung microvascular pressure was shown to increase
      endothelial [Ca(2+)](i) via activation of transient receptor potential vanilloid
      4 (TRPV4) channels. The endothelial [Ca(2+)](i) transient increased K(f) via
      activation of myosin light-chain kinase and simultaneously stimulated NO
      synthesis. In TRPV4 deficient mice, pressure-induced increases in endothelial
      [Ca(2+)](i), NO synthesis, and lung wet/dry weight ratio were largely blocked.
      Endothelial NO formation limited the permeability increase by a cGMP-dependent
      attenuation of the pressure-induced [Ca(2+)](i) response. Inactivation of TRPV4
      channels by cGMP was confirmed by whole-cell patch-clamp of pulmonary
      microvascular endothelial cells and intravital imaging of endothelial
      [Ca(2+)](i). Hence, pressure-induced endothelial Ca(2+) influx via TRPV4 channels
      increases lung vascular permeability yet concomitantly activates an NO-mediated
      negative-feedback loop that protects the vascular barrier by a cGMP-dependent
      attenuation of the endothelial [Ca(2+)](i) response. The identification of this
      novel regulatory pathway gives rise to new treatment strategies, as demonstrated
      in vivo in rats with acute myocardial infarction in which inhibition of cGMP
      degradation by the phosphodiesterase 5 inhibitor sildenafil reduced hydrostatic
      lung edema.

PMID- 18323528
TI  - Acceleration of cardiovascular disease by a dysfunctional prostacyclin receptor
      mutation: potential implications for cyclooxygenase-2 inhibition.
AB  - Recent increased adverse cardiovascular events observed with selective
      cyclooxygenase-2 inhibition led to the withdrawal of rofecoxib (Vioxx) and
      valdecoxib (Bextra), but the mechanisms underlying these atherothrombotic events
      remain unclear. Prostacyclin is the major end product of cyclooxygenase-2 in
      vascular endothelium. Using a naturally occurring mutation in the prostacyclin
      receptor, we report for the first time that a deficiency in prostacyclin
      signaling through its G protein-coupled receptor contributes to atherothrombosis
      in human patients. We report that a prostacyclin receptor variant (R212C) is
      defective in adenylyl cyclase activation in both patient blood and in an in vitro
      COS-1 overexpression system. This promotes increased platelet aggregation, a
      hallmark of atherothrombosis. Our analysis of patients in 3 separate white
      cohorts reveals that this dysfunctional receptor is not likely an initiating
      factor in cardiovascular disease but that it accelerates the course of disease in
      those patients with the greatest risk factors. R212C was associated with
      cardiovascular disease only in the high cardiovascular risk cohort (n=980), with
      no association in the low-risk cohort (n=2293). In those at highest
      cardiovascular risk, both disease severity and adverse cardiovascular events were
      significantly increased with R212C when compared with age- and risk factor
      matched normal allele patients. We conclude that for haploinsufficient mutants,
      such as the R212C, the enhanced atherothrombotic phenotype is likely dependent on
      the presence of existing atherosclerosis or injury (high risk factors), analogous
      to what has been observed in the cyclooxygenase-2 inhibition studies or
      prostacyclin receptor knockout mice studies. Combining both biochemical and
      clinical approaches, we conclude that diminished prostacyclin receptor signaling
      may contribute, in part, to the underlying adverse cardiovascular outcomes
      observed with cyclooxygenase-2 inhibition.

PMID- 18323529
TI  - Oxygen deprivation triggers upregulation of early growth response-1 by the
      receptor for advanced glycation end products.
AB  - Myocardial infarction, stroke, and venous thromboembolism are characterized by
      oxygen deprivation. In hypoxia, biological responses are activated that evoke
      tissue damage. Rapid activation of early growth response-1 in hypoxia upregulates
      fundamental inflammatory and prothrombotic stress genes. We probed the mechanisms
      mediating regulation of early growth response-1 and demonstrate that hypoxia
      stimulates brisk generation of advanced glycation end products (AGEs) by
      endothelial cells. Via AGE interaction with their chief signaling receptor, RAGE,
      membrane translocation of protein kinase C-betaII occurs, provoking
      phosphorylation of c-Jun NH(2)-terminal kinase and increased transcription of
      early growth response-1 and its downstream target genes. These findings identify
      RAGE as a master regulator of tissue stress elicited by hypoxia and highlight
      this receptor as a central therapeutic target to suppress the tissue injury
      provoking effects of oxygen deprivation.

PMID- 18323530
TI  - Cyclic AMP: master regulator of innate immune cell function.
AB  - Cyclic adenosine monophosphate (cAMP) was the original "second messenger" to be
      discovered. Its formation is promoted by adenylyl cyclase activation after
      ligation of G protein-coupled receptors by ligands including hormones, autocoids,
      prostaglandins, and pharmacologic agents. Increases in intracellular cAMP
      generally suppress innate immune functions, including inflammatory mediator
      generation and the phagocytosis and killing of microbes. The importance of the
      host cAMP axis in regulating antimicrobial defense is underscored by the fact
      that microbes have evolved virulence-enhancing strategies that exploit it. Many
      clinical situations that predispose to infection are associated with increases in
      cAMP, and therapeutic strategies to interrupt cAMP generation or actions have
      immunostimulatory potential. This article reviews the anatomy of the cAMP axis,
      the mechanisms by which it controls phagocyte immune function, microbial
      strategies to dysregulate it, and its clinical relevance.

PMID- 18323532
TI  - Leukotriene D4 up-regulates furin expression through CysLT1 receptor signaling.
AB  - Leukotriene (LT)D(4) is suggested to play a role in airway remodeling, which is
      characterized by fibrogenesis and airway smooth muscle cell hyperplasia. In this
      study, we investigated the effects of LTD(4) on the expression of furin, a
      proprotein convertase involved in the maturation/activation of several substrates
      implicated in the remodeling processes. HEK293 cells stably transfected with the
      CysLT1 receptor were used to study the transcriptional regulation of furin by
      LTD(4). Stimulation of the cells with LTD(4) resulted in a time- and
      concentration-dependent induction of furin mRNA and protein expression. The study
      of furin gene (fur) promoters P1, P1A, and P1B revealed a selective
      transactivation of the P1 promoter by LTD(4). Mutations in the activator protein
      (AP)-1-binding element of the P1 promoter resulted in the partial loss of
      transactivation by LTD(4). Binding of AP-1 transcription factor to fur P1
      promoter after stimulation with LTD(4) was demonstrated by electrophoretic
      mobility shift assay, and supershift assays indicated the formation of c-Jun/c
      Fos complexes. LTD(4) induced the maturation of the furin substrates membrane
      type 1 matrix metalloproteinase and transforming growth factor-beta1, which was
      inhibited by the furin inhibitor alpha1-PDX. Finally, LTD(4) induced furin gene
      expression in monocytic THP-1 cells, which was abrogated using a selective CysLT1
      receptor antagonist and inhibitors of the mitogen-activated protein kinases MEK
      1, p38, and JunK. Our data show for the first time that LTD(4), via the CysLT1
      receptor, can transcriptionally activate furin production with consequent
      maturation of furin substrates relevant to airway remodeling. These findings
      suggest that CysLT1 is involved in remodeling processes through modulation of
      furin transcription.

PMID- 18323531
TI  - Deletion of caveolin-1 protects against oxidative lung injury via up-regulation
      of heme oxygenase-1.
AB  - Acute lung injury (ALI) is a major cause of morbidity and mortality in critically
      ill patients. Hyperoxia causes lung injury in animals and humans, and is an
      established model of ALI. Caveolin-1, a major constituent of caveolae, regulates
      numerous biological processes, including cell death and proliferation. Here we
      demonstrate that caveolin-1-null mice (cav-1(-/-)) were resistant to hyperoxia
      induced death and lung injury. Cav-1(-/-) mice sustained reduced lung injury
      after hyperoxia as determined by protein levels in bronchoalveolar lavage fluid
      and histologic analysis. Furthermore, cav-1(-/-) fibroblasts and endothelial
      cells and cav-1 knockdown epithelial cells resisted hyperoxia-induced cell death
      in vitro. Basal and inducible expression of the stress protein heme oxygenase-1
      (HO-1) were markedly elevated in lung tissue or fibroblasts from cav-1(-/-) mice.
      Hyperoxia induced the physical interaction between cav-1 and HO-1 in fibroblasts
      assessed by co-immunoprecipitation studies, which resulted in attenuation of HO
      activity. Inhibition of HO activity with tin protoporphyrin-IX abolished the
      survival benefits of cav-1(-/-) cells and cav-1(-/-) mice exposed to hyperoxia.
      The cav-1(-/-) mice displayed elevated phospho-p38 mitogen-activated protein
      kinase (MAPK) and p38beta expression in lung tissue/cells under basal conditions
      and during hyperoxia. Treatment with SB202190, an inhibitor of p38 MAPK,
      decreased hyperoxia-inducible HO-1 expression in wild-type and cav-1(-/-)
      fibroblasts. Taken together, our data demonstrated that cav-1 deletion protects
      against hyperoxia-induced lung injury, involving in part the modulation of the HO
      1-cav-1 interaction, and the enhanced induction of HO-1 through a p38 MAPK
      mediated pathway. These studies identify caveolin-1 as a novel component involved
      in hyperoxia-induced lung injury.

PMID- 18323533
TI  - Spatiotemporal expression of flk-1 in pulmonary epithelial cells during lung
      development.
AB  - Vascular endothelial growth factor-A (VEGF-A) responsive effects mediated via the
      receptors fetal liver kinase-1 (flk-1) and fms-like tyrosine kinase (flt-1), are
      key processes of pulmonary vascular development. Flk-1 has been shown to be
      involved in early embryonic lung epithelial to endothelial crosstalk and
      branching morphogenesis. Recent reports suggested a role of VEGF-A in lung
      epithelial cell function. Based on these observations, we hypothesize that
      epithelial flk-1 has a unique function in pulmonary development. Thus, the aim of
      this study is to elucidate spatiotemporal expression of flk-1 during lung
      development with respect to the epithelial system. Embryonic lungs were screened
      for flk-1 messenger RNA and protein at daily intervals, including postnatal
      stages. From Embryonic Day (ED) 12.5 through ED 15.5, flk-1 expression was
      restricted to the early vascular primitive network, while from ED 16.5 on flk-1
      was detectable in the epithelial system and persisted there postnatally. At
      postnatal stages, flk-1 expression was increasingly restricted to individual
      cells in the alveolar septa. Isolation and in vitro cultivation of alveolar
      epithelial cells confirmed flk-1 expression and showed VEGF secretion into the
      supernatant. To our knowledge, this is the first murine study characterizing
      epithelial flk-1 expression at different stages throughout lung organogenesis
      until birth and at postnatal stages. To confirm epithelial flk-1 expression, we
      performed reporter gene analysis of the flk-1 promoter in vivo. Investigations on
      transgenic mouse strains, containing either a complete or incomplete flk-1
      promoter driving expression of the lacZ reporter gene, suggested differential flk
      1 regulation in endothelial and epithelial cells.

PMID- 18323534
TI  - Sustained expression of alpha1-antitrypsin after transplantation of manipulated
      hematopoietic stem cells.
AB  - Inherited mutations in the human alpha(1)-antitrypsin (AAT) gene lead to
      deficient circulating levels of AAT protein and a predisposition to developing
      emphysema. Gene therapy for individuals deficient in AAT is an attractive goal,
      because transfer of a normal AAT gene into any cell type able to secrete AAT
      should reverse deficient AAT levels and attenuate progression of lung disease.
      Here we present an approach for AAT gene transfer based on the transplantation of
      lentivirally transduced hematopoietic stem cells (HSCs). We develop a novel dual
      promoter lentiviral system to transfer normal human AAT cDNA as well as a
      fluorescent tracking "reporter gene" into murine HSCs. After transplantation of
      3,000 transduced HSCs into irradiated mouse recipients, we demonstrate
      simultaneous and sustained systemic expression of both genes in vivo for at least
      31 weeks. The stem cells transduced with this protocol maintain multipotency,
      self-renewal potential, and the ability to reconstitute the hematopoietic systems
      of both primary and secondary recipients. This lentiviral-based system may be
      useful for investigations requiring the systemic secretion of anti-proteases or
      cytokines relevant to the pathogenesis of a variety of lung diseases.

PMID- 18323535
TI  - Using drama to prevent teen smoking: development, implementation, and evaluation
      of crossroads in Hawai'i.
AB  - The use of drama as a preventive education measure has demonstrated success in
      various health promotion venues and offers promise in promoting positive youth
      attitudes and behavior change related to tobacco use. Especially important is a
      need to implement culturally relevant methods to reach youth. This article
      describes the development and implementation of a tobacco prevention drama for
      Asian and Pacific Islander youth. The resulting play, Crossroads, features a soap
      opera-style drama interspersed with humorous vignettes and multimedia effects and
      incorporates cultural cues, mannerisms, dress, and values consistent with Asian
      and Pacific Islander youth culture. Evaluation data indicate that the drama has
      an effect on audience knowledge, attitudes, and intended behavior, including a
      change in future intent to smoke cigarettes and the ability of audience members
      to develop connections with the characters in the play and apply concepts that
      are presented in the play to their own lives.

PMID- 18323536
TI  - Assessing the scientific accuracy, readability, and cultural appropriateness of a
      culturally targeted smoking cessation program for American Indians.
AB  - This study assesses educational materials developed for the All Nations Breath of
      Life smoking cessation program (targeted for American Indians and Alaska Natives)
      for scientific accuracy, readability and other literacy factors, and cultural
      appropriateness. The authors used a scientific review panel of experts in smoking
      cessation representing epidemiology, medicine, and psychology; the suitability
      assessment of materials (SAM) and the simplified measure of gobbledygook (SMOG)
      reading grade level formulas; and review by Native program facilitators and pilot
      participants. Materials were scientifically accurate and culturally appropriate.
      The mean SAM score was 80% (superior rating), and the average reading grade level
      was 7.1 using the Fry formula (part of the SAM) and 8.4 using the SMOG formula
      (difference was not statistically significant). Based on this project, the SAM
      can be used in combination with scientific review and input from community
      members during formative research to assess and modify educational materials for
      a targeted population.

PMID- 18323537
TI  - Comparative analysis of the small RNA transcriptomes of Pinus contorta and Oryza
      sativa.
AB  - The diversity of microRNAs and small-interfering RNAs has been extensively
      explored within angiosperms by focusing on a few key organisms such as Oryza
      sativa and Arabidopsis thaliana. A deeper division of the plants is defined by
      the radiation of the angiosperms and gymnosperms, with the latter comprising the
      commercially important conifers. The conifers are expected to provide important
      information regarding the evolution of highly conserved small regulatory RNAs.
      Deep sequencing provides the means to characterize and quantitatively profile
      small RNAs in understudied organisms such as these. Pyrosequencing of small RNAs
      from O. sativa revealed, as expected, approximately 21- and approximately 24-nt
      RNAs. The former contained known microRNAs, and the latter largely comprised
      intergenic-derived sequences likely representing heterochromatin siRNAs. In
      contrast, sequences from Pinus contorta were dominated by 21-nt small RNAs. Using
      a novel sequence-based clustering algorithm, we identified sequences belonging to
      18 highly conserved microRNA families in P. contorta as well as numerous clusters
      of conserved small RNAs of unknown function. Using multiple methods, including
      expressed sequence folding and machine learning algorithms, we found a further 53
      candidate novel microRNA families, 51 appearing specific to the P. contorta
      library. In addition, alignment of small RNA sequences to the O. sativa genome
      revealed six perfectly conserved classes of small RNA that included chloroplast
      transcripts and specific types of genomic repeats. The conservation of microRNAs
      and other small RNAs between the conifers and the angiosperms indicates that
      important RNA silencing processes were highly developed in the earliest
      spermatophytes. Genomic mapping of all sequences to the O. sativa genome can be
      viewed at http://microrna.bcgsc.ca/cgi-bin/gbrowse/rice_build_3/.

PMID- 18323538
TI  - Detecting polymorphic regions in Arabidopsis thaliana with resequencing
      microarrays.
AB  - Whole-genome oligonucleotide resequencing arrays have allowed the comprehensive
      discovery of single nucleotide polymorphisms (SNPs) in eukaryotic genomes of
      moderate to large size. With this technology, the detection rate for isolated
      SNPs is typically high. However, it is greatly reduced when other polymorphisms
      are located near a SNP as multiple mismatches inhibit hybridization to arrayed
      oligonucleotides. Contiguous tracts of suppressed hybridization therefore typify
      polymorphic regions (PRs) such as clusters of SNPs or deletions. We developed a
      machine learning method, designated margin-based prediction of polymorphic
      regions (mPPR), to predict PRs from resequencing array data. Conceptually similar
      to hidden Markov models, the method is trained with discriminative learning
      techniques related to support vector machines, and accurately identifies even
      very short polymorphic tracts (<10 bp). We applied this method to resequencing
      array data previously generated for the euchromatic genomes of 20 strains
      (accessions) of the best-characterized plant, Arabidopsis thaliana.
      Nonredundantly, 27% of the genome was included within the boundaries of PRs
      predicted at high specificity ( approximately 97%). The resulting data set
      provides a fine-scale view of polymorphic sequences in A. thaliana; patterns of
      polymorphism not apparent in SNP data were readily detected, especially for
      noncoding regions. Our predictions provide a valuable resource for evolutionary
      genetic and functional studies in A. thaliana, and our method is applicable to
      similar data sets in other species. More broadly, our computational approach can
      be applied to other segmentation tasks related to the analysis of genomic
      variation.

PMID- 18323539
TI  - The mucosal immune response to laryngopharyngeal reflux.
AB  - RATIONALE: Laryngopharyngeal reflux (LPR) affects up to 20% of Western
      populations. Although individual morbidity is usually moderate, treatment costs
      are high and there are associations with other diseases, including laryngeal
      cancer. To date, there have been no studies of the mucosal immune response to
      this common inflammatory disease. OBJECTIVES: To determine the mucosal immune
      response to LPR. METHODS: We performed a prospective immunologic study of
      laryngeal biopsies from patients with LPR and control subjects (n = 12 and 11,
      respectively), and of primary laryngeal epithelial cells in vitro. MEASUREMENTS
      AND MAIN RESULTS: Quantitative multiple-color immunofluorescence, using
      antibodies for lymphocytes (CD4, CD8, CD3, CD79, CD161), granulocytes (CD68,
      EMBP), monocytic cells (CD68, major histocompatibility complex [MHC] class II),
      and classical and nonclassical MHC (I, II, beta(2)-microglobulin, CD1d).
      Univariate and multivariate analysis and colocalization measurements were
      applied. There was an increase in percentage area of mucosal CD8(+) cells in the
      epithelium (P < 0.005), whereas other leukocyte and granulocyte antigens were
      unchanged. Although epithelial MHC class I and II expression was unchanged by
      reflux, expression of the nonclassical MHC molecule CD1d increased (P < 0.05,
      luminal layers). In vitro, laryngeal epithelial cells constitutively expressed
      CD1d. CD1d and MHC I expression were inversely related in all subjects, in a
      pattern which appears to be unique to the upper airway. Colocalization of natural
      killer T (NKT) cells with CD1d increased in patients (P < 0.01). CONCLUSIONS:
      These data indicate a role for the CD1d-NKT cell axis in response to LPR in
      humans. This represents a useful target for novel diagnostics and treatments in
      this common condition.

PMID- 18323540
TI  - Ethnic differences in adolescent lung function: anthropometric, socioeconomic,
      and psychosocial factors.
AB  - RATIONALE: The relative contribution of body proportion and social exposures to
      ethnic differences in lung function has not previously been reported in the
      United Kingdom. OBJECTIVES: To examine ethnic differences in lung function in
      relation to anthropometry and social and psychosocial factors in early
      adolescence. METHODS: The subjects of this study were 3,924 pupils aged 11 to 13
      years, of whom 80% were ethnic minorities with satisfactory lung function
      measures. Data were collected on economic disadvantage, psychological well-being,
      tobacco exposure, height, FEV(1), and FVC. MEASUREMENTS AND MAIN RESULTS: The
      lowest FEV(1) was observed for Black Caribbean/African children after adjusting
      for standing height (SH) (white boys: 2.475 L; 95% confidence interval [CI],
      2.442-2.509; white girls: 2.449 L; 95% CI, 2.464-2.535]; Black Caribbean boys: 
      14% [95% CI, -16 to -12]; Black Caribbean girls: -13% [95% CI, -16 to -11]; Black
      African boys: -15% [95% CI, -17 to -13]; Black African girls: -17% [95% CI, -19
      to -14]; Indian boys: -13% [95% CI, -16 to -11]; Indian girls: -11% [95% CI, -14
      to -8]; Pakistani/Bangladeshi boys: -7% [95% CI, -9 to -5]; Pakistani/Bangladeshi
      girls: -9% [95% CI, -11 to -6]). Adjustment for upper body segment instead of SH
      achieved a further reduction in ethnic differences of 41 to 51% for children of
      Black African origin and 26 to 39% for the other groups. Overcrowding (boys) and
      poor psychological well-being (boys and girls) were independent correlates of
      FEV(1), explaining up to a further 10% of ethnic differences. Similar patterns
      were observed for FVC. Social exposures were also related to height components.
      CONCLUSIONS: Differences in upper body segment explained more of the ethnic
      differences in lung function than SH, particularly among Black Caribbeans/African
      subjects. Social correlates had a smaller but significant impact. Future research
      needs to consider how differential development of lung capacity is compromised by
      the social patterning of growth trajectories.

PMID- 18323541
TI  - Differences in accuracy of 99mTc-sestamibi scanning between severe and mild forms
      of primary hyperparathyroidism.
AB  - Preoperative localization of the parathyroids using (99m)Tc-sestamibi scanning
      has not yet been established as a routine diagnostic procedure for primary
      hyperparathyroidism. Several studies have demonstrated a variable degree of
      accuracy (70%-98%) in asymptomatic patients. METHODS: We evaluated the accuracy
      of this technique in 64 patients who underwent scanning between January 2000 and
      January 2005 according to the clinical manifestations of the disease. RESULTS:
      The study included 25 asymptomatic patients (group I), 18 nephrolithiasis
      patients without overt bone disease (group II), and 21 patients with severe bone
      involvement and osteitis fibrosa cystica (group III). Mean serum calcium in
      groups I, II, and III was 10.98 +/- 0.02, 11.32 +/- 0.17, and 13.35 +/- 0.35
      mg/dL, respectively. Mean serum parathyroid hormone in groups I, II, and III was
      135.45 +/- 13.50, 165.85 +/- 15.06, and 579.6 +/- 628.4 pg/mL, respectively. The
      (99m)Tc-sestamibi scan results were positive in 64% of the patients in group I,
      in 83% of those in group II, and in 100% of those in group III. Of the patients
      with severe bone disease, 70% showed increased uptake on the initial images,
      whereas in the other groups, increased uptake was seen only on the delayed
      images, as expected. CONCLUSION: Our data show a high degree of accuracy for the
      use of (99m)Tc-sestamibi scanning as a localizing procedure in severe primary
      hyperparathyroidism.

PMID- 18323542
TI  - Immunophenotyping of chronic lymphoid leukemias.

PMID- 18323543
TI  - Measuring circulating tumor cells as a surrogate end point for adjuvant therapy
      of breast cancer: what do they mean and what should we do about them?

PMID- 18323544
TI  - Weighing a dose-dense option for adjuvant chemotherapy and trastuzumab in early
      stage breast cancer.

PMID- 18323545
TI  - Monitoring the response of circulating epithelial tumor cells to adjuvant
      chemotherapy in breast cancer allows detection of patients at risk of early
      relapse.
AB  - PURPOSE: To demonstrate that it is possible to monitor the response to adjuvant
      therapy by repeated analysis of circulating epithelial tumor cells (CETCs) and to
      detect patients early who are at risk of relapse. PATIENTS AND METHODS: In 91
      nonmetastatic primary breast cancer patients, CETCs were quantified using laser
      scanning cytometry of anti-epithelial cell adhesion molecule-stained epithelial
      cells from whole unseparated blood before and during adjuvant chemotherapy.
      RESULTS: Numbers of CETCs were analyzed before therapy, before each new cycle,
      and at the end of chemotherapy. The following three typical patterns of response
      were observed: (1) decrease in cell numbers (> 10-fold); (2) marginal changes in
      cell numbers (< 10-fold); and (3) an (sometimes saw-toothed) increase or an
      initial decrease with subsequent reincrease (> 10-fold) in numbers of CETCs.
      Twenty relapses (22%) were observed within the accrual time of 40 months,
      including one of 28 patients from response group 1, five of 30 patients from
      response group 2, and 14 of 33 patients from response group 3. The difference in
      relapse-free survival was highly significant for CETC (hazard ratio = 4.407; 95%
      CI, 1.739 to 9.418; P < .001) between patients with decreasing cell numbers and
      those with marginal changes and between patients with marginal changes and those
      with an increase of more than 10-fold (linear Cox regression model). CONCLUSION:
      These results show that peripherally circulating tumor cells are influenced by
      systemic chemotherapy and that an increase (even after initial response to
      therapy) of 10-fold or more at the end of therapy is a strong predictor of
      relapse and a surrogate marker for the aggressiveness of the tumor cells.

PMID- 18323546
TI  - The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel
      with trastuzumab in HER-2/neu overexpressed/amplified breast cancer.
AB  - PURPOSE: Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by
      paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the
      demonstrated cardiac safety for trastuzumab (T) with conventionally scheduled AC
      followed by P, we tested the safety of dd AC followed by P with T. The primary
      end point was cardiac safety, and the secondary end points were time to
      recurrence and overall survival. METHODS: Patients with HER-2/neu
      immunohistochemistry (IHC) 3+ or fluorescent in situ hybridization (FISH)
      amplified breast cancer and baseline left ventricular ejection fraction (LVEF) of
      >or= 55% were enrolled, regardless of tumor size or nodal status. Treatment
      consisted of AC (60/600 mg/m(2)) x 4 followed by P (175 mg/m(2)) x 4 every 2
      weekly with pegfilgrastim (6 mg on day 2) + T x1 year. LVEF by radionuclide scan
      was obtained at baseline, at months 2, 6, 9, and 18. RESULTS: From January 2005
      to November 2005, 70 patients were enrolled. The median age was 49 years (range,
      27 to 72 years); median LVEF at baseline was 68% (range, 55% to 81%). At month 2
      in 70 of 70 patients, the median LVEF was 67% (range, 58% to 79%); at month 6 in
      67 of 70 patients, it was 66% (range, 52% to 75%); at month 9 in 68 of 70
      patients, it was 65% (range, 50% to 75%); and at month 18 in 48 of 70 patients,
      it was 66% (range, 57% to 75%). As of December 1, 2007, the median follow-up was
      28 months (range, 25 to 35 months). One patient (1%) experienced congestive heart
      failure (CHF). There were no cardiac deaths. CONCLUSION: Dose-dense AC followed
      by P/T followed by T is feasible and is not likely to increase the incidence of
      cardiac events compared to established regimens.

PMID- 18323547
TI  - Risk of new primary nonbreast cancers after breast cancer treatment: a Dutch
      population-based study.
AB  - PURPOSE: To assess the risk of secondary nonbreast cancers (SNBCs) in a recently
      treated population-based cohort of breast cancer patients focused on the
      association with treatment and prognostic implications. PATIENTS AND METHODS: In
      58,068 Dutch patients diagnosed with invasive breast cancer between 1989 and
      2003, SNBC risk was quantified using standardized incidence ratios (SIRs),
      cumulative incidence, and Cox regression analysis, adjusted for competing risks.
      RESULTS: After a median follow-up of 5.4 years, 2,578 SNBCs had occurred.
      Compared with the Dutch female population at large, in this cohort, the SIR of
      SNBCs was increased (SIR, 1.22; 95% CI, 1.17 to 1.27). The absolute excess risk
      was 13.6 (95% CI, 9.7 to 17.6) per 10,000 person-years. SIRs were elevated for
      cancers of the esophagus, stomach, colon, rectum, lung, uterus, ovary, kidney,
      and bladder cancers, and for soft tissue sarcomas (STS), melanoma, non-Hodgkin's
      lymphoma, and acute myeloid leukemia (AML). The 10-year cumulative incidence of
      SNBCs was 5.4% (95% CI, 5.1% to 5.7%). Among patients younger than 50 years,
      radiotherapy was associated with an increased lung cancer risk (hazard ratio [HR]
      = 2.31; 95% CI, 1.15 to 4.60) and chemotherapy with decreased risk for all SNBCs
      (HR = 0.78; 95% CI, 0.63 to 0.98) and for colon and lung cancer. Among patients
      age 50 years and older, radiotherapy was associated with raised STS risk (HR =
      3.43; 95% CI, 1.46 to 8.04); chemotherapy with increased risks of melanoma,
      uterine cancer, and AML; and hormonal therapy with all SNBCs combined (HR = 1.10;
      95% CI, 1.01 to 1.21) and uterine cancer (HR = 1.78; 95% CI, 1.40 to 2.27). An
      SNBC worsened survival (HR = 3.98; 95%CI 3.77 to 4.20). CONCLUSION: Breast cancer
      patients diagnosed in the 1990 s experienced a small but significant excess risk
      of developing an SNBC.

PMID- 18323548
TI  - Treatment of advanced hormone-sensitive breast cancer in postmenopausal women
      with exemestane alone or in combination with celecoxib.
AB  - PURPOSE: Preclinical data showed that the combination of exemestane and celecoxib
      has synergistic effects. Therefore, a study was undertaken to explore the
      efficacy and tolerability of this combination in postmenopausal patients with
      advanced, hormone-sensitive breast cancer. PATIENTS AND METHODS: A randomized
      phase II study was conducted in postmenopausal patients with hormone-sensitive
      breast cancer and measurable disease who had progressive disease after treatment
      with tamoxifen. Patients were randomly assigned to either exemestane 25 mg daily
      or the combination of exemestane 25 mg daily with celecoxib 400 mg twice daily.
      Response Evaluation Criteria in Solid Tumors Group criteria were used to
      determine antitumor efficacy. Primary end point was the rate of clinical benefit.
      Secondary end points were tolerability, objective response rate, time to
      progression (TTP), and duration of clinical benefit. A pharmacodynamic and a
      pharmacokinetic study were conducted in parallel. RESULTS: One hundred eleven
      patients (exemestane, n = 55; combination, n = 56) were enrolled in 2002. The
      demographic characteristics and prognostic factors were similar in both arms. In
      the assessable population, 24 of 51 patients in the combination arm and 24 of 49
      patients in the exemestane arm achieved clinical benefit. TTP was similar in both
      groups. Duration of clinical benefit was longer in the combination group (median,
      96.6 v 49.1 weeks). The addition of celecoxib did not change the tolerability
      profile of exemestane alone. CONCLUSION: Similar rates of clinical benefit were
      achieved in both groups.

PMID- 18323549
TI  - Use of different postmenopausal hormone therapies and risk of histology- and
      hormone receptor-defined invasive breast cancer.
AB  - PURPOSE: We previously found that the risk of invasive breast cancer varied
      according to the progestagen component of combined postmenopausal hormone therapy
      (CHT): progesterone, dydrogesterone, or other progestagens. We conducted the
      present study to assess how these CHTs were associated with histology- and
      hormone receptor-defined breast cancer. PATIENTS AND METHODS: We used data from
      the French E3N cohort study, with 80,391 postmenopausal women followed for a mean
      duration of 8.1 years; 2,265 histologically confirmed invasive breast cancers
      were identified through biennial self-administered questionnaires completed from
      1990 to 2002. The relative risks (RRs) were estimated using Cox proportional
      hazards models. RESULTS: Compared with postmenopausal hormone therapy (HT) never
      use, ever-use of estrogen+progesterone was not significantly associated with the
      risk of any breast cancer subtype, but increasing duration of
      estrogen+progesterone was associated with increasing risks of lobular (P = .06)
      and estrogen receptor-positive/progesterone receptor-negative (ER+/PR-; P = .02).
      Estrogen+dydrogesterone was associated with a significant increase in risk of
      lobular carcinoma (RR, 1.7; 95% CI, 1.1 to 2.6). Estrogen+other progestagens was
      associated with significant increases in risk of ductal and lobular carcinomas
      (RR, 1.6; 95% CI, 1.3 to 1.8; and 2.0; 95% CI, 1.5 to 2.7, respectively), of
      ER+/PR+ and ER+/PR- carcinomas (RR, 1.8; 95% CI, 1.5 to 2.1; and 2.6; 95% CI, 1.9
      to 3.5, respectively), but not of ER-/PR+ or ER-/PR- carcinomas (RR, 1.0; 95% CI,
      0.5 to 2.1; and 1.4; 95% CI, 0.9 to 2.0, respectively). CONCLUSION: The increase
      in risk of breast cancer observed with the use of CHTs other than
      estrogen+progesterone and estrogen+dydrogesterone seems to apply preferentially
      to ER+ carcinomas, especially those ER+/PR-, and to affect both ductal and
      lobular carcinomas.

PMID- 18323550
TI  - The body image and relationships scale: development and validation of a measure
      of body image in female breast cancer survivors.
AB  - PURPOSE: A self-report measure of body image in female breast cancer survivors,
      the Body Image and Relationships Scale (BIRS), was developed to address attitudes
      about appearance, health, physical strength, sexuality, relationships, and social
      functioning following treatment. METHODS: The 32-item measure, generated by
      expert consensus and revised based on focus group feedback, was administered to
      95 female breast cancer participants twice within 1 to 2 weeks. Test-retest
      reliability, internal consistency, and validity of the measure were assessed
      using standard-scale construction techniques. The structure of the proposed
      measure was evaluated using exploratory factor analysis. Associations of the
      resulting factors and other variables were assessed using extreme groups
      analyses. RESULTS: The BIRS had satisfactory test-retest reliability and internal
      consistency. Principal axis factoring revealed three factors: (1) health and
      strength, (2) social barriers, and (3) appearance and sexuality. Correlations of
      the subscales with standardized measures of related constructs were significant
      and in the anticipated directions. Extreme groups analyses suggested associations
      between less physical activity and more impairment on factors 1 and 3,
      premenopausal status at first diagnosis and more impairment on factor 2, and
      younger age at the time of survey administration and more impairment on factor 3.
      CONCLUSION: The proposed scale demonstrated satisfactory reliability and internal
      consistency. Factor analysis revealed three subscales with coherent item content
      and differential associations with measures of activity level, menopause status,
      and age. Observed relationships with other measures support convergent and
      divergent validity. Results suggest that the proposed scale is useful for
      clinical and research applications.

PMID- 18323551
TI  - Effect of race on the outcome of pediatric patients with Hodgkin's lymphoma.
AB  - PURPOSE: Some cooperative groups have found a survival disadvantage in black
      children with various childhood cancers. We examine the effects of race on
      clinical outcomes among children with Hodgkin's lymphoma (HL) treated with
      contemporary therapy at a tertiary care children's hospital. PATIENTS AND
      METHODS: Retrospective analysis of 327 children and adolescents diagnosed with HL
      between 1990 and 2005. Patients were treated with risk-directed multimodal
      therapy regardless of race, ethnicity, or ability to pay. Event-free and overall
      survival rates were compared for black and white children. Clinical
      characteristics, socioeconomic factors, and biologic features were analyzed for
      prognosis of treatment failure. RESULTS: The 262 white and 65 black patients did
      not differ significantly in presenting features, clinical characteristics, or
      enrollment in a clinical trial. More black patients (71% v 45%) resided in poor
      counties (P < .001). While black and white children were equally likely to have
      progressive disease or early relapse, black children were 3.7 times (95% CI, 1.7
      to 8.0) more likely to relapse 12 months or more after diagnosis. The 5-year
      event-free survival was 71% +/- 6.1% (SE) for black and 84% +/- 2.4% for white
      children (P = .01). However, the 5-year survival rate did not differ between
      white and black children (94.4% v 94.7%). While black race and low hemoglobin
      concentration were independent predictors of treatment failure, only low
      hemoglobin concentration independently predicted poor survival. CONCLUSION: Black
      children with Hodgkin's lymphoma have lower event-free survival than white
      children, but both populations have the same 5-year overall survival.

PMID- 18323552
TI  - Predictors of depressed mood in spouses of women with breast cancer.
AB  - PURPOSE: Depressed mood in spouses of women with breast cancer deleteriously
      affects their own and their wife's functioning and their marital communication.
      However, no study has examined why some spouses get depressed whereas others do
      not, particularly during the first months of diagnosis and treatment, a known
      difficult time for couples. The current study has two purposes: to test a
      predictive model of spouses' depressed mood and to evaluate the model's accuracy
      in distinguishing between normal and clinically depressed spouses. METHODS: Data
      were obtained from standardized questionnaires completed by 206 spouses and 206
      wives recently diagnosed with nonmetastatic breast cancer. Spouses' depressed
      mood was measured by the Center for Epidemiological Studies-Depression Scale. A
      total of 19 variables were extracted from the literature for testing in the
      model, including psychological, social, demographic, and disease- and treatment
      related variables. RESULTS: Spouses were more likely to be depressed if they were
      older, less well educated, more recently married, reported heightened fears over
      their wife's well-being, worried about their job performance, were more uncertain
      about their future, or were in less well-adjusted marriages. The model correctly
      classified 89.2% of spouses' mood (chi(2) = 79.1; P < .001). CONCLUSION: Spouses
      of women with local or regional breast cancer need to be screened for depressed
      mood and triaged into supportive services to better assist them manage the threat
      of their wife's breast cancer.

PMID- 18323553
TI  - How should we design supportive cancer care? The patient's perspective.
AB  - PURPOSE: Hospice services are designed to meet the needs of patients near the end
      of life. Although so-called open-access hospice programs and bridge programs are
      beginning to offer these services to patients who are still receiving treatment,
      it is not known whether they best meet patients' needs. PATIENTS AND METHODS:
      Three hundred adult patients receiving treatment for cancer completed interviews
      in which each patient's value or ability for supportive care services were
      calculated from the choices that they made among combinations of those services.
      Preferences for five traditional hospice services and six alternative supportive
      care services were measured, and patients were followed up for 6 months or until
      death. RESULTS: Patients' utilities for alternative services were higher than
      those for traditional hospice services (0.53 v 0.39; sign-rank test P < .001).
      Alternative services were also preferred among patients with poor functional
      status (Eastern Cooperative Oncology Group performance score > 2; n = 54; 0.65 v
      0.48; P < .001) and among those who were in the last 6 months of life (0.68 v
      0.56; sign-rank test P = .003). Even patients who were willing to forgo cancer
      treatment (n = 38; 13%) preferred alternative services (3.1 v 1.8; P < .001).
      CONCLUSION: Patients who are receiving active treatment for cancer, and even
      those who are willing to stop treatment, express a clear preference for
      alternative supportive care services over traditional hospice services.
      Supportive care programs for patients with advanced cancer should reconsider the
      services that they offer and might seek to include novel services in addition to,
      or perhaps instead of, traditional hospice services.

PMID- 18323554
TI  - Job loss and re-employment of cancer patients in Korean employees: a nationwide
      retrospective cohort study.
AB  - PURPOSE: The aim of this study was to investigate whether a diagnosis of cancer
      has an impact on the cancer patients' job loss and re-employment and to identify
      the factors affecting job loss and re-employment during 6 years of follow-up of
      Korean employees with cancer. PATIENTS AND METHODS: All employees except for the
      self-employed in Korea who were diagnosed with cancer during the 2001 calendar
      year (n = 5,396) were identified as the first baseline patients and were followed
      every 3 months over 6 years to estimate the time taken to job loss. Patients who
      lost their job within the first year after a diagnosis of cancer (n = 1,398) were
      identified as the second baseline patients and were followed up over 5 years to
      estimate the time taken to re-employment using the National Health Insurance
      claims data. Patient demographic, socioeconomic, and clinical variables were
      investigated as factors that affected job loss and re-employment. RESULTS: Among
      the first baseline cancer patients, 47.0% lost their job, and among the second
      baseline patients, 30.5% were re-employed over 69 to 72 months of follow-up.
      Female sex, younger age and older age, company employee, lower income, blood
      cancer, and brain and CNS, lung, and liver cancer were significant predictors of
      early job loss or delayed re-employment. CONCLUSION: The diagnosis of cancer
      affects cancer patients' employment status differently according to different
      factors: sex, age, type of job, income, and cancer site. Efforts should be made
      to support re-employment and reduce unnecessary work cessation and disparity
      between different demographic and socioeconomic groups of cancer survivors.

PMID- 18323555
TI  - Understanding of prognosis and goals of care among couples whose child died of
      cancer.
AB  - PURPOSE: Little is known about how couples care for the terminally ill child with
      cancer. We assessed both parents' understanding of prognosis and treatment goals
      for children with cancer and explored whether sex mediates these views. We also
      investigated whether discordance within couples regarding treatment goals was
      related to parental perception of the child's end-of-life (EOL) experience.
      METHODS: We surveyed mothers and fathers of children who died of cancer and were
      cared for at Children's Hospital (Boston, MA) and the Dana-Farber Cancer
      Institute (Boston, MA) between 2000 and 2004. Our sample included 38 couples
      (response rate, 56%). RESULTS: Willingness to participate did not differ by sex.
      At diagnosis, fathers and mothers held a similar understanding of the child's
      prognosis, and 58% of couples agreed on the goal of cure. During the EOL period,
      a majority of fathers and mothers reported lessening suffering as the primary
      goal. However, within couples there was poor agreement about the primary goal of
      care (kappa = 0.07). When parents did not agree on the primary goal of lessening
      suffering, both parents were more likely to report that the child suffered
      significantly from cancer-directed treatment (P = .03). CONCLUSION: Though parent
      goals are often concurrent at diagnosis, they frequently differ during the EOL
      period. Parent disagreement about the goal of lessening suffering at the EOL
      appears to impact how parents describe their child's experience of suffering.
      Creating opportunities for parents to work through their goals together may lead
      to improvements in the child's EOL experience.

PMID- 18323556
TI  - Targeting vascular endothelial growth factor in advanced carcinoid tumor: a
      random assignment phase II study of depot octreotide with bevacizumab and
      pegylated interferon alpha-2b.
AB  - PURPOSE: Effective systemic therapy for advanced carcinoid is lacking. The
      combination of bevacizumab (BEV) and pegylated (PEG) interferon alpha-2b was
      evaluated among patients with metastatic or unresectable carcinoid tumors.
      PATIENTS AND METHODS: Forty-four patients on stable doses of octreotide were
      randomly assigned to 18 weeks of treatment with bevacizumab or PEG interferon
      alpha-2b. At disease progression (PD) or at the end of 18 weeks (whichever
      occurred earlier), patients received bevacizumab plus PEG interferon until
      progression. Functional computer tomography (CT) scans were performed to measure
      effect on tumor blood flow. RESULTS: In the bevacizumab arm, four patients (18%)
      achieved confirmed partial response (PR), 17 patients (77%) had stable disease
      (SD), and one patient (5%) had PD. In the PEG interferon arm, 15 patients (68%)
      had SD and six patients (27%) had PD. Progression-free survival (PFS) rates after
      18 weeks of monotherapy were 95% in bevacizumab versus 68% on the PEG interferon
      arm. The overall median PFS for all 44 patients is 63 weeks. Compared with paired
      baseline measurements on functional CT scans, we observed a 49% (P < .01) and 28%
      (P < .01) decrease in tumor blood flow at day 2 and week 18 among patients
      treated with bevacizumab. No significant changes in tumor blood flow were
      observed following PEG interferon. PEG interferon alpha-2b treatment was
      associated with decrease in plasma basic fibroblast growth factor (bFGF; P = .04)
      and increase in plasma interleukin-18 (IL-18; P < .01). No significant changes in
      bFGF or IL-18 following treatment with bevacizumab were observed. CONCLUSION:
      Bevacizumab therapy resulted in objective responses, reduction of tumor blood
      flow, and longer PFS in patients with carcinoid than PEG interferon treatment.

PMID- 18323557
TI  - Nomograms to predict serious adverse events in phase II clinical trials of
      molecularly targeted agents.
AB  - PURPOSE: A tool that quantifies the risk of treatment-related toxicity based on
      individual patient characteristics can augment the informed consent process and
      safety monitoring in the setting of phase II cancer treatment trials of
      molecularly targeted agents (MTAs). METHODS: A regression model was constructed
      to predict the risk of a serious adverse event (SAE) with an MTA and presented as
      a nomogram. Estimation of risk can be performed by integrating risk estimates
      from the nomogram and from a reference or average patient. Internal validation
      was performed using bootstrapping techniques. RESULTS: A total of 578 patients
      were treated with one of 14 MTAs given alone or in combination on one of 27
      clinical trials performed by the Princess Margaret Hospital Drug Development
      Program between 2001 and 2006. Approximately 50% and 24% of patients experienced
      an SAE and an attributable SAE (SAEatt) during cycle 1, respectively. Albumin,
      lactate dehydrogenase (LDH), number of target lesions, prior radiotherapy,
      Charlson score, age, and performance status were included in the optimal model as
      predictors of a cycle 1 SAE, whereas the number of prior chemotherapy regimens,
      baseline creatinine, LDH, prior radiotherapy, Charlson score, body-surface area,
      and performance status were included as predictors of an SAEatt. Moderate-good
      internal validity was demonstrated, with area under the curve estimates ranging
      from 56.7% to 86.1% for all SAEs and 63.0% to 89.7% for SAEatts. CONCLUSION: A
      regression model was constructed that predicts the SAE and SAEatt risk for an
      individual patient during cycle 1 of phase II trial treatment with moderate to
      good internal validity. External validation is still required.

PMID- 18323558
TI  - Role of extent of resection in the long-term outcome of low-grade hemispheric
      gliomas.
AB  - PURPOSE: The prognostic role of extent of resection (EOR) of low-grade gliomas
      (LGGs) is a major controversy. We designed a retrospective study to assess the
      influence of EOR on long-term outcomes of LGGs. PATIENTS AND METHODS: The study
      population (N = 216) included adults undergoing initial resection of hemispheric
      LGG. Region-of-interest analysis was performed to measure tumor volumes based on
      fluid-attenuated inversion-recovery (FLAIR) imaging. RESULTS: Median preoperative
      and postoperative tumor volumes and EOR were 36.6 cm(3) (range, 0.7 to 246.1
      cm(3)), 3.7 cm(3) (range, 0 to 197.8 cm(3)) and 88.0% (range, 5% to 100%),
      respectively. There was no operative mortality. New postoperative deficits were
      noted in 36 patients (17%); however, all but four had complete recovery. There
      were 34 deaths (16%; median follow-up, 4.4 years). Progression and malignant
      progression were identified in 95 (44%) and 44 (20%) cases, respectively.
      Patients with at least 90% EOR had 5- and 8-year overall survival (OS) rates of
      97% and 91%, respectively, whereas patients with less than 90% EOR had 5- and 8
      year OS rates of 76% and 60%, respectively. After adjusting each measure of tumor
      burden for age, Karnofsky performance score (KPS), tumor location, and tumor
      subtype, OS was predicted by EOR (hazard ratio [HR] = 0.972; 95% CI, 0.960 to
      0.983; P < .001), log preoperative tumor volume (HR = 4.442; 95% CI, 1.601 to
      12.320; P = .004), and postoperative tumor volume (HR = 1.010; 95% CI, 1.001 to
      1.019; P = .03), progression-free survival was predicted by log preoperative
      tumor volume (HR = 2.711; 95% CI, 1.590 to 4.623; P <or= .001) and postoperative
      tumor volume (HR = 1.007; 95% CI, 1.001 to 1.014; P = .035), and malignant
      progression-free survival was predicted by EOR (HR = 0.983; 95% CI, 0.972 to
      0.995; P = .005) and log preoperative tumor volume (HR = 3.826; 95% CI, 1.632 to
      8.969; P = .002). CONCLUSION: Improved outcome among adult patients with
      hemispheric LGG is predicted by greater EOR.

PMID- 18323559
TI  - How to build and interpret a nomogram for cancer prognosis.
AB  - Nomograms are widely used for cancer prognosis, primarily because of their
      ability to reduce statistical predictive models into a single numerical estimate
      of the probability of an event, such as death or recurrence, that is tailored to
      the profile of an individual patient. User-friendly graphical interfaces for
      generating these estimates facilitate the use of nomograms during clinical
      encounters to inform clinical decision making. However, the statistical
      underpinnings of these models require careful scrutiny, and the degree of
      uncertainty surrounding the point estimates requires attention. This guide
      provides a nonstatistical audience with a methodological approach for building,
      interpreting, and using nomograms to estimate cancer prognosis or other health
      outcomes.

PMID- 18323560
TI  - Plasma cell dyscrasia presenting as ascites and omental mass.

PMID- 18323561
TI  - Sepsis from liver abscesses in metastatic colorectal carcinoma after
      chemoimmunotherapy.

PMID- 18323562
TI  - Marantic endocarditis and disseminated intravascular coagulation with systemic
      emboli in presentation of pancreatic cancer.

PMID- 18323563
TI  - Role of palifermin in fluorouracil-based therapy for metastatic colorectal
      cancer.

PMID- 18323564
TI  - Long overdue: phase II studies in older cancer patients: where does the FDA
      stand?

PMID- 18323565
TI  - Cancer in Nevada's adolescent and young adult population.

PMID- 18323566
TI  - Activated NF-kB in colorectal cancer: predictive or prognostic factor?

PMID- 18323567
TI  - Coronary artery disease after radiation therapy for early breast cancer.

PMID- 18323568
TI  - Does postoperative radiation therapy benefit patients with prostate cancer?

PMID- 18323569
TI  - Activation of CB1 specifically located on GABAergic interneurons inhibits LTD in
      the lateral amygdala.
AB  - Previously, we found that in the lateral amygdala (LA) of the mouse, WIN55,212-2
      decreases both glutamatergic and GABAergic synaptic transmission via activation
      of the cannabinoid receptor type 1 (CB1), yet produces an overall reduction of
      neuronal excitability. This suggests that the effects on excitatory transmission
      override those on inhibitory transmission. Here we show that CB1 activation by
      WIN55,212-2 and Delta(9)-THC inhibits long-term depression (LTD) of basal
      synaptic transmission in the LA, induced by low-frequency stimulation (LFS; 900
      pulses/1 Hz). The CB1 agonist WIN55,212-2 blocked LTD via G(i/o) proteins,
      activation of inwardly rectifying K+ channels (K(ir)s), inhibition of the
      adenylate cyclase-protein kinase A (PKA) pathway, and PKA-dependent inhibition of
      voltage-gated N-type Ca2+ channels (N-type VGCCs). Interestingly, WIN55,212-2
      effects on LTD were abolished in CB1 knock-out mice (CB1-KO), and in conditional
      mutants lacking CB1 expression only in GABAergic interneurons, but were still
      present in mutants lacking CB1 in principal forebrain neurons. LTD induction per
      se was unaffected by the CB1 antagonist SR141716A and was normally expressed in
      CB1-KO as well as in both conditional CB1 mutants. Our data demonstrate that
      activation of CB1 specifically located on GABAergic interneurons inhibits LTD in
      the LA. These findings suggest that CB1 expressed on either glutamatergic or
      GABAergic neurons play a differential role in the control of synaptic
      transmission and plasticity.

PMID- 18323570
TI  - Prenatal choline supplementation alters the timing, emotion, and memory
      performance (TEMP) of adult male and female rats as indexed by differential
      reinforcement of low-rate schedule behavior.
AB  - Choline availability in the maternal diet has a lasting effect on brain and
      behavior of the offspring. To further delineate the impact of early nutritional
      status, we examined effects of prenatal-choline supplementation on timing,
      emotion, and memory performance of adult male and female rats. Rats that were
      given sufficient choline (CON: 1.1 g/kg) or supplemental choline (SUP: 5.0 g/kg)
      during embryonic days (ED) 12-17 were trained with a differential reinforcement
      of low-rate (DRL) schedule that was gradually transitioned through 5-, 10-, 18-,
      36-, and 72-sec criterion times. We observed that SUP-females emitted more
      reinforced responses than CON-females, which were more efficient than both groups
      of males. In addition, SUP-males and SUP-females exhibited a reduction in burst
      responding (response latencies <2 sec) compared with both groups of CON rats.
      Furthermore, despite a reduced level of burst responding, the SUP-males made more
      nonreinforced responses prior to the DRL criterion as a result of maintaining the
      previous DRL criterion following transition to a new criterion. In summary, long
      lasting effects of prenatal-choline supplementation were exhibited by reduced
      frustrative DRL responding in conjunction with the persistence of temporal memory
      in SUP-males and enhanced temporal exploration and response efficiency in SUP
      females.

PMID- 18323571
TI  - Critical role of the 65-kDa isoform of glutamic acid decarboxylase in
      consolidation and generalization of Pavlovian fear memory.
AB  - Evidence suggests that plasticity of the amygdalar and hippocampal GABAergic
      system is critical for fear memory formation. In this study we investigated in
      wild-type and genetically manipulated mice the role of the activity-dependent 65
      kDa isozyme of glutamic acid decarboxylase (GAD65) in the consolidation and
      generalization of conditioned fear. First, we demonstrate a transient reduction
      of GAD65 gene expression in the dorsal hippocampus (6 h post training) and in the
      basolateral complex of the amygdala (24 h post training) during distinct phases
      of fear memory consolidation. Second, we show that targeted ablation of the GAD65
      gene in Gad65(-/-) mice results in a pronounced context-independent, intramodal
      generalization of auditory fear memory during long-term (24 h or 14 d) but not
      short-term (30 min) memory retrieval. The temporal specificity of both gene
      regulation and memory deficits in Gad65 mutant mice suggests that GAD65-mediated
      GABA synthesis is critical for the consolidation of stimulus-specific fear
      memory. This function appears to involve a modulation of neural activity patterns
      in the amygdalo-hippocampal pathway as indicated by a reduction in theta
      frequency synchronization between the amygdala and hippocampus of Gad65(-/-) mice
      during the expression of generalized fear memory.

PMID- 18323572
TI  - Immediate memory consequences of the effect of emotion on attention to pictures.
AB  - Emotionally arousing stimuli are at once both highly attention grabbing and
      memorable. We examined whether emotional enhancement of memory (EEM) reflects an
      indirect effect of emotion on memory, mediated by enhanced attention to emotional
      items during encoding. We tested a critical prediction of the mediation
      hypothesis-that regions conjointly activated by emotion and attention would
      correlate with subsequent EEM. Participants were scanned with fMRI while they
      watched emotional or neutral pictures under instructions to attend to them a lot
      or a little, and were then given an immediate recognition test. A region in the
      left fusiform gyrus was activated by emotion, voluntary attention, and subsequent
      EEM. A functional network, different for each attention condition, connected this
      region and the amygdala, which was associated with emotion and EEM, but not with
      voluntary attention. These findings support an indirect cortical mediation
      account of immediate EEM that may complement a direct modulation model.

PMID- 18323573
TI  - Safety, pharmacokinetics, and pharmacodynamics of oral apoA-I mimetic peptide D
      4F in high-risk cardiovascular patients.
AB  - Patients with coronary heart disease or equivalent risk received a single dose of
      30, 100, 300, or 500 mg of unformulated D-4F (n = 8, each dose) or placebo (n =
      8) under fasting conditions. An additional 10 patients received 500 mg (n = 8) or
      placebo (n = 2) with a low-fat meal. There were no significant trends in any
      safety parameter. D-4F was detectable in plasma at all doses with a T(max) of 30
      min, 1 h, and 2 h for 30, 100, and > or = 300 mg, respectively. The area under
      the curve((0-t)) was 27.81 ng/hr/ml and 54.71 ng/hr/ml for the 300 mg and 500 mg
      dose groups, respectively, and 17.96 ng/hr/ml for the 500 mg dose given with
      food. HDL from each time point for each subject was tested for its ability to
      inhibit LDL-induced monocyte chemotactic activity in cultures of human aortic
      endothelial cells. The values obtained were normalized to 1.0 for LDL alone to
      obtain the HDL inflammatory index. This index significantly improved at 4 h at
      the 300 mg dose and at 2 h at the 500 mg dose compared with placebo (P < 0.05).
      There were no changes in plasma lipid or lipoprotein levels. We conclude that
      unformulated D-4F has low bioavailability that is improved under fasting
      conditions, and that a single dose of D-4F is safe and well tolerated and may
      improve the HDL anti-inflammatory index.

PMID- 18323575
TI  - Introduction: challenges in microbial quality control for nonhuman primate.

PMID- 18323574
TI  - Apolipoprotein A-I mimetic peptide helix number and helix linker influence
      potentially anti-atherogenic properties.
AB  - We hypothesize that apolipoprotein A-I (apoA-I) mimetic peptides better mimicking
      the punctuated alpha-helical repeats of full-length apoA-I are more anti
      inflammatory and anti-atherogenic. This study compares a monomeric apoA-I mimetic
      helix to three different tandem helix peptides in vitro: 4F (18 mer), 4F-proline
      4F (37 mer, Pro), 4F-alanine-4F (37 mer, Ala), and 4F-KVEPLRA-4F [the human apoA
      I 4/5 interhelical sequence (IHS), 43 mer]. All peptides cleared turbid lipid
      suspensions, with 4F being most effective. In contrast to lipid clearance, tandem
      peptides were more effective at remodeling mouse HDL. All four peptides displaced
      apoA-I and apoE from the HDL, leaving a larger particle containing apoA-II and
      peptide. Peptide-remodeled HDL particles show no deficit in ABCG1 cholesterol
      efflux despite the loss of the majority of apoA-I. Tandem peptides show greater
      ability to efflux cholesterol from lipid-loaded murine macrophages, compared with
      4F. Although 4F inhibited oxidation of purified mouse LDL, the Ala tandem peptide
      increased oxidation. We compared several tandem 4F-based peptides with monomeric
      4F in assays that correlated with suggested anti-inflammatory/anti-atherogenic
      pathways. Tandem 4F-based peptides, which better mimic full-length apoA-I, exceed
      monomeric 4F in HDL remodeling and cholesterol efflux but not LDL oxidation
      protection. In addition, apoA-I mimetic peptides may increase reverse cholesterol
      transport through both ABCA1 as well as ABCG1 pathways.

PMID- 18323576
TI  - Specific pathogen-free macaques: definition, history, and current production.
AB  - Specific pathogen-free (SPF) macaque colonies are now requested frequently as a
      resource for research. Such colonies were originally conceived as a means to cull
      diseased animals from research-dedicated colonies, with the goal of eliminating
      debilitating or fatal infectious agents from the colony to improve the
      reproductive capacity of captive research animals. The initial pathogen of
      concern was Mycobacterium tuberculosis (M.tb.), recognized for many years as a
      pathogen of nonhuman primates as well as a human health target. More recently
      attention has focused on four viral pathogens as the basis for an SPF colony:
      simian type D retrovirus (SRV), simian immunodeficiency virus (SIV), simian T
      cell lymphotropic/leukemia virus (STLV), and Cercopithecine herpesvirus 1 (CHV
      1). New technologies, breeding, and maintenance schemes have emerged to develop
      and provide SPF primates for research. In this review we focus on the nonhuman
      primates (NHPs) most common to North American NHP research facilities, Asian
      macaques, and the most common current research application of these animals,
      modeling of human AIDS.

PMID- 18323577
TI  - Nonhuman primate quarantine: its evolution and practice.
AB  - Nonhuman primates (NHPs) are imported to the United States for use in research,
      domestic breeding, and propagation of endangered populations in zoological
      gardens. During the past 60 years, individuals responsible for NHP importation
      programs have observed morbidity and mortality typically associated with
      infectious disease outbreaks. These outbreaks have included infectious agents
      such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus
      infections such as the Ebola and Marburg viruses. Some outbreaks have affected
      both animal and human populations. These epizootics are attributable to a variety
      of factors, including increased population density, exposure of naive populations
      to new infectious agents, and stress. The practice of quarantining animals
      arriving in the United States was first applied by individual research programs
      to improve animal health and ensure the quality of animals entering research
      programs. The development of government regulations for nonhuman primate
      quarantine accompanied the recognition that imported NHPs could pose a risk to
      public health. This article briefly reviews the history of US NHP importation and
      the factors behind the development of NHP quarantine regulations. The focus is on
      regulations concerned with infectious disease, public health, and the health of
      domestic primate colonies. These regulations have had the dual benefit of
      protecting public health as well as reducing animal morbidity and mortality
      during importation and quarantine. We review current practices and facilities for
      nonhuman primate quarantine and identify challenges for the future.

PMID- 18323578
TI  - Development, application, and quality control of serology assays used for
      diagnostic monitoring of laboratory nonhuman primates.
AB  - The careful development, validation, and implementation of serodiagnostic assays
      can provide reliable results that make them a valuable tool in microbial quality
      control for nonhuman primates. This article includes identification and
      description of the components of assay development, including formulas for
      calculating the number of positive serum samples needed for assay validation and
      methods for calculating their diagnostic sensitivity and specificity. To ensure
      that assays are performing within predetermined specifications, there must be a
      quality control system that includes appropriate system and sample suitability
      controls as well as mechanisms to track assay performance over time. The section
      on quality assurance includes definitions of precision and accuracy in assay
      performance, and how to interpret these two factors using the Levey-Jennings
      chart, Westgard's rules, and other monitoring methods. Because all serologic
      assays are prone to false positive and false negative results, it is essential to
      interpret all diagnostic test results using both the expected prevalence of
      disease in the population and the population-specific assay performance
      characteristics that are determined during assay validation. The discussion on
      interpreting diagnostic test results also includes guidelines for calculating the
      positive and negative predictive values of an assay and for interpreting results
      based on the disease prevalence of the test population. A glossary provides
      definitions of commonly used terms.

PMID- 18323579
TI  - New approaches to tuberculosis surveillance in nonhuman primates.
AB  - Despite significant progress in reducing the incidence of tuberculosis in
      nonhuman primates (NHPs) maintained in captivity, outbreaks continue to occur in
      established colonies, with potential serious consequences in human exposures,
      animal losses, disruption of research, and costs related to disease control
      efforts. The intradermal tuberculin skin test (TST) using mammalian old
      tuberculin (MOT) has been the mainstay of NHP tuberculosis surveillance and
      antemortem diagnosis for more than 60 years. But limitations of the TST,
      particularly its inability to reliably identify animals with latent TB
      infections, make it unsuitable for use as a single, standalone test for TB
      surveillance in nonhuman primates in the 21st century. Advances in technology and
      the availability of Mycobacterium spp. genomic sequence data have facilitated the
      development and evaluation of new immune-based screening assays as possible
      adjuncts and alternatives to the TST, including in vitro whole blood assays that
      measure the release of interferon gamma in response to stimulation with
      tuberculin or specific mycobacterial antigens, and assays that detect antibodies
      to highly immunogenic secreted proteins unique to M. tuberculosis, M. bovis, and
      other species belonging to the M. tuberculosis complex. It is becoming apparent
      that no single screening test will meet all the requirements for surveillance and
      diagnosis of tuberculosis in nonhuman primates. Instead, the use of several tests
      in combination can increase the overall sensitivity and specificity of screening
      and surveillance programs and likely represents the future of TB testing in
      nonhuman primates. In this article we describe the characteristics of these newer
      screening tests and discuss their potential contributions to NHP tuberculosis
      surveillance programs.

PMID- 18323580
TI  - Impact of infections and normal flora in nonhuman primates on drug development.
AB  - Preclinical safety studies that are required for the marketing approval of a
      pharmaceutical include single and repeat dose studies in rodent and nonrodent
      species. The use of nonhuman primates (NHPs), primarily macaques, as the
      nonrodent species has increased in recent years, in part due to the increase in
      development of biopharmaceuticals and immunomodulatory agents. Depending on the
      source of the macaques, they may vary in genetic background, normal flora, and/or
      the incidence of preexisting pathogens and inflammatory conditions. As the use of
      alternative sources of macaques rises to meet the increased demand for these
      animals in biomedical research, the toxicologic pathologist should be well versed
      in NHP pathology to adequately assess potential drug-related effects in the
      context of these variations. Such knowledge is particularly important in studies
      involving immunomodulatory drugs as the toxicologic pathologist should anticipate
      which type(s) of infections are most likely to arise depending on which arm of
      the immune system is modulated. The purpose of this review is to discuss the
      immunosuppressive (e.g., simian type D retrovirus, simian immunodeficiency virus)
      and opportunistic viruses (e.g., cytomegalovirus, adenovirus, simian virus 40,
      rhesus rhadinovirus, and lymphocryptovirus), primary and opportunistic bacteria
      (e.g., Campylobacter spp., Shigella flexneri, Yersinia enterocolitica, Moraxella
      catarrhalis, Mycobacterium avium complex, enteropathogenic Escherichia coli), and
      parasites (e.g., Plasmodium spp., Schistosoma spp., Strongyloides fulleborni)
      that have had the most profound impact on the interpretation of drug safety
      studies and/or that may reemerge as alternative sources of NHPs are used for drug
      safety studies.

PMID- 18323581
TI  - Opportunistic infections in immunologically compromised nonhuman primates.
AB  - Despite advances in the husbandry of nonhuman primates, natural and
      experimentally induced diseases continue to pose risks to animal health. These
      risks are particularly important when such disease results in immunodeficient
      states that provide an opportunity for the development of opportunistic
      infections. Because opportunistic agents may serve as significant confounders to
      research and hold potential for zoonotic transmission, knowledge of disease
      pathogenesis, surveillance, and risk reduction is particularly important to
      individuals who work closely with primates. Endogenous diseases of primates that
      result in blunted immune responses and thus allow for the development of
      opportunistic infection include simian type D retroviruses and measles. In
      addition, simian immunodeficiency virus is a frequently studied experimental
      cause of immunosuppression. This article focuses on clinical and pathological
      aspects of the most common opportunistic infections that occur in nonhuman
      primates maintained in research settings. The complete elimination of all
      infectious agents from primate colonies may be impossible and unwarranted, but
      microbial surveillance programs can help both to define the complement of agents
      present in a colony and to elucidate their potential impacts on colony health,
      zoonotic risk, and experimental research. We discuss risk reduction through the
      use of quarantine procedures, specific pathogen-free animals, and environmental
      controls.

PMID- 18323583
TI  - Macaque models of human infectious disease.
AB  - Macaques have served as models for more than 70 human infectious diseases of
      diverse etiologies, including a multitude of agents-bacteria, viruses, fungi,
      parasites, prions. The remarkable diversity of human infectious diseases that
      have been modeled in the macaque includes global, childhood, and tropical
      diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative
      neurologic, potential bioterrorism, and miscellaneous other diseases.
      Historically, macaques played a major role in establishing the etiology of yellow
      fever, polio, and prion diseases. With rare exceptions (Chagas disease,
      bartonellosis), all of the infectious diseases in this review are of Old World
      origin. Perhaps most surprising is the large number of tropical (16), newly
      emergent (7), and bioterrorism diseases (9) that have been modeled in macaques.
      Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a
      consequence of zoonotic infection. However, infectious agents of certain
      diseases, including measles and tuberculosis, can sometimes go both ways, and
      thus several human pathogens are threats to nonhuman primates including macaques.
      Through experimental studies in macaques, researchers have gained insight into
      pathogenic mechanisms and novel treatment and vaccine approaches for many human
      infectious diseases, most notably acquired immunodeficiency syndrome (AIDS),
      which is caused by infection with human immunodeficiency virus (HIV). Other
      infectious agents for which macaques have been a uniquely valuable resource for
      biomedical research, and particularly vaccinology, include influenza virus,
      paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus,
      smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia
      pestis, and Plasmodium species. This review summarizes the extensive past and
      present research on macaque models of human infectious disease.

PMID- 18323582
TI  - Nonhuman primate infections after organ transplantation.
AB  - Nonhuman primates, primarily rhesus macaques (Macaca mulatta), cynomolgus
      macaques (Macaca fascicularis), and baboons (Papio spp.), have been used
      extensively in research models of solid organ transplantation, mainly because the
      nonhuman primate (NHP) immune system closely resembles that of the human.
      Nonhuman primates are also frequently the model of choice for preclinical testing
      of new immunosuppressive strategies. But the management of post-transplant
      nonhuman primates is complex, because it often involves multiple
      immunosuppressive agents, many of which are new and have unknown effects.
      Additionally, the resulting immunosuppression carries a risk of infectious
      complications, which are challenging to diagnose. Last, because of the natural
      tendency of animals to hide signs of weakness, infectious complications may not
      be obvious until the animal becomes severely ill. For these reasons the diagnosis
      of infectious complications is difficult among post-transplant NHPs. Because most
      nonhuman primate studies in organ transplantation are quite small, there are only
      a few published reports concerning infections after transplantation in nonhuman
      primates. Based on our survey of these reports, the incidence of infection in NHP
      transplant models is 14%. The majority of reports suggest that many of these
      infections are due to reactivation of viruses endemic to the primate species,
      such as cytomegalovirus (CMV), polyomavirus, and Epstein-Barr virus (EBV)-related
      infections. In this review, we address the epidemiology, pathogenesis, role of
      prophylaxis, clinical presentation, and treatment of infectious complications
      after solid organ transplantation in nonhuman primates.

PMID- 18323584
TI  - [Beneficial effects of Hartil on cardiovascular remodeling process in elderly and
      old patients with isolated systolic arterial hypertension].
AB  - The aim of present study was to assess antihypertensive efficacy of ramipril 5-10
      mg (Hartil "EGIS", Hungary) and its influence on hemodynamical changes and vessel
      endothelial function in old and elderly patients with isolated systolic
      hypertension. 32 patients were studied. The duration of the therapy was 6 months.
      24-hour blood pressure monitoring was performed and left ventricular parameters,
      systolic, diastolic function and endothelial function of brachial artery
      (endothelium - dependent vasodilatation), blood tests, lipid profile were
      investigated before and after 3 and 6-months of treatment. The study detected
      high antihypertensive efficacy of Hartil: mean daily and pulse pressure were
      significantly (p<0,001) decreased after 3 and 6-months of treatment (TA(syst) 9,1
      and 16%, TA(diast) 2,2 and 8,4%, pulse pressure 2,2 and 7,5%, respectively),
      beneficial effect revealed on 24-hour blood pressure profile: number of patients
      with normal dipper profile increase from 33 to 46% with decrease of number of non
      dippers and night-peakers. During study tendency of left ventricular mass/index
      reduction was detected. That become statistically significant (p<0,001) after 6
      months of treatment (11,7/11,4%), consequently increased number of patients with
      concentric remodelling (from 18,7 to 25%) and normal geometry (from 12,5 to
      18,7%), and decreased number of patients with concentric hypertrophy (from 31,3
      to 25%) and eccentric hypertrophy (from 37,5 to 31,3%). Also there was
      significant (p<0,05) improvement of diastolic and endothelial functions (up to
      28,7 and 45,5%, respectively) and increase of number of patients with normal
      endothelial function (from 25 to 53%). Data of laboratory tests revealed
      metabolic neutrality of Hartil. Thus, Hartil (5-10 mg daily) revealed high
      antihypertensive efficacy, metabolic neutrality and beneficial effects on
      cardiovascular remodeling process in old and elderly patients with isolated
      systolic hypertension, which contributes to reduce the risk of cardiovascular
      complications.

PMID- 18323585
TI  - [Efficacy of adipin and normodipin (generic drugs of amlodipine) vs norvsc in
      treatment of essential hypertension].
AB  - It's well known, that norvsc - a very effective and popular cardiovascular
      medication - has many generic analogs. The reason of our study was to compare the
      efficacy and safety of adipin ("GMP", Georgia), normodipin ("Gedeon Richter",
      Hungary) and norvasc ("Pfizer", USA) in patients with essential hypertension
      (stage I-II, JNC VII). The study was performed using ambulatory blood pressure
      monitoring (ABPM), the data from which closely correlate with end-organ damage in
      hypertension and provides excellent information about hypotensive drug effect on
      the circadian rhythm of blood pressure and its adequate control. It was open
      liable, crossover, comparative, prospective trial in 20 patients. Our data
      confirm that generic drugs adipin and normodipine are as effective and safe as
      original norvasc in treatment of patients with hypertension.

PMID- 18323586
TI  - [Clinical efficacy and safety of Zo-20 in patients with ischemic heart disease].
AB  - Since their introduction in the late 1980s, the 3- hydroxy-3 -methilglutaryl
      coenzyme A (HMG -CoA) reductaze inhibitors or statins, have revolutionized the
      treatment of hyperlipidemia. Despite the well-recognized benefits of statins,
      there is evidence that low density lipoprotein cholesterol (LDL-C) reductions as
      specified by National Cholesterol Education Program (NCEP) are not being met. The
      aim of the study was to assess the efficacy of Zo-20 ("GMP", Georgia) in
      achieving the target level for LDL-C in patients with CAD and
      hypercholesterinemia. 100 patients received 20-40 mg Zo-20 during the 3 months
      period, all parameters of the blood plasma lipids and adverse events were
      monitored during the study. 78% of patients reached the target goal for LDL-C,
      using 28,2 mg Zo-20 daily. No serious adverse events associated with study drug
      treatment were revealed. Zo-20 seems to be very effective and safety in treatment
      of patients with CAD and lipid disorders.

PMID- 18323587
TI  - [Clinical report of posterior leukoencephalopathy syndrome].
AB  - The article describes the case history of posterior leukoencephalopathy syndrome 
      a brain disorder that predominantly affects the cerebral white matter. Edematous
      lesions involve the posterior parietal and occipital lobes, and may spread to
      basal ganglia, brain stem and cerebellum. This rapidly evolving neurological
      condition is clinically characterized by headache, nausea and vomiting, seizures,
      visual disturbances and altered sensorial functions, and occasionally focal
      neurological deficit. Posterior leukoencephalopathy syndrome is often associated
      with an abrupt increase in blood pressure and is usually seen in patients with
      eclampsia, renal disease and hypertensive encephalopathy. It is also seen in the
      patients treated with cytotoxic and immunosuppressive drugs such as cyclosporine
      A, tacrolimus /FK-506, cisplatin, cytarabine, IVIg, erytrophoietin, and
      interferon alpha. The study demonstrated that lesions of posterior
      leukoencephalopathy syndrome are best visualized with magnetic resonance [MR]
      imaging. T2 weighted MR Images, at the height of symptoms, characteristically
      show diffuse hyper intensity selectively involving the parieto - occipital white
      matter. Occasionally the lesions also involve the grey matter. Computed
      tomography can also be used satisfactorily to detect hypodense lesions of
      posterior leukoencephalopathy. Early recognition of this condition is of
      paramount importance because prompt control of blood pressure, withdrawal of
      immunosuppressive agents will cause reversal of the syndrome. Delay in the
      diagnosis and treatment can result in permanent damage to affected brain tissues.
      The clinical data and radiological findings depicted in the study add to the
      investigation of the disorder.

PMID- 18323588
TI  - [The relation of insulin resistance with the complications of diabetes mellitus
      type 2 and metabolic parameters].
AB  - The aim of our investigation was to study the relation of insulin resistance (IR)
      with the complications of diabetes mellitus type 2 (DM2) and metabolic
      parameters. 44 patients with DM2 (mean age - 49,1+/-8,7 years) have been
      investigated. The parameters of carbohydrate metabolism, HOMA-indices, parameters
      of lipid metabolism and blood pressure have been determined. I group consisted of
      32 patients with high mean value of HOMA-IR (2,6+/-0,8), and II group - 12
      patients with lower mean value of HOMA-IR (0,9+/-0,3). The IHD frequency was
      significantly lower in II group (OR=0,20 (0,40-0,95)); and sum of macrovascular
      complications was significantly frequent in I group, i.e. in patients with IR
      (OR=9,71 (1,12-84,30)). In patients with IR serum C-peptide, triglycerides, HDL
      cholesterol levels, sistolic blood pressure, body mass index and waist
      circumference were significantly differed from analogous parameters of patients
      without IR. IR significantly impact on the development of macrovascular
      complications of DM2 and significantly worsen the parameters of carbohydrate and
      lipid metabolism, blood pressure and body mass. Therefore, we conclude that in
      addition to the good glycemic control the important goal of the treatment of DM2
      is the reduction of insulin resistance (introduction of insulin sensitizing
      agents, physical activity, body mass reduction, the decrease of daily insulin
      injecting doses).

PMID- 18323589
TI  - [The influence of high levels of endogenous and exogenous insulin on the
      complications of type 2 diabetes and metabolic parameters].
AB  - The aim of our investigation was to study the influence of high levels of
      endogenous and exogenous insulin on the complications of type 2 diabetes and
      metabolic parameters. 62 patients with DM2 (mean age - 50,2+/-9,7 years) have
      been investigated. The parameters of carbohydrate metabolism, HOMA-indices,
      parameters of lipid metabolism, blood pressure, BMI and waist circumference have
      been determined. I group consisted of 19 patients with high levels of endogenous
      insulin (C-peptide - 3,3+/-0,5 ng/ml) and daily exogenous insulin doses (65,2+/
      17,7 units); II group - 26 patients with moderate levels of endogenous insulin (C
      peptide - 1,6+/-0,8 ng/ml) and daily exogenous insulin doses (48,7+/-11,7 units);
      and III group - low levels of endogenous insulin (C-peptide - 0,4+/-0,4 ng/ml)
      and daily exogenous insulin doses (36,3+/-5,7 units). The IHD frequency was
      significantly higher in I group in comparison with II and III [OR=6,00 (1,54
      23,30) and OR=5,36 (1,24-23,21), respectively]; and sum of macrovascular
      complications was significantly frequent in I group [OR=10,20 (2,50-41,39) and
      OR=8,13 (1,87-35,23)). In patients with high levels of serum C-peptide and daily
      doses of exogenous insulin HOMA indices, triglycerides, HDL-cholesterol levels,
      body mass index and waist circumference were significantly differed from
      analogous parameters of patients of other groups. High values of endogenous and
      exogenous insulin significantly impact on the development of macrovascular
      complications of DM2 and significantly worsen the parameters of lipid metabolism
      and body mass. On the basis of obtained data we conclude that in addition to the
      good glycemic control the important goal of the treatment of DM2 is the control
      of insulinemia.

PMID- 18323590
TI  - [Some aspects of metabolic remodeling of myocard during chronic heart failure].
AB  - Review provides different mechanisms of "metabolic remodeling" of myocard during
      Chronic Heart Failure (CHF) including disorder of myocardial energy metabolism,
      changed activity of intracellular regulatory enzymes, metabolic activity of
      myocardial interstitium, different metabolic pathways leading to apoptosis of
      cardiomyocytes. The liquidation of results "metabolic remodeling"of myocardium
      prospects the new possibilities for development of pharmacological modulators of
      myocardial metabolic dysfunction in CHF.

PMID- 18323591
TI  - [Holisal in the complex treatment of periodontal disease].
AB  - The aim of our research was to evaluate efficiency of medicine Cholisal in
      complex treatment of periodontitis. During the research 36 patients with
      periodontitis (from 18 to 36 years old) were examined and treated. The patients
      were divided into 3 groups according to severity of periodontitis. Each group
      included 12 patients. For studying the efficiency of treatment both objective and
      subjective data was used. In case of mild severity of disease clinical indices
      were: HI=2,1+/-0,75; Ghi=1,4+/-0,67; Gi=1,7+/-0,78, PI=0,8+/-0,34. In case of
      moderate severity of disease clinical indices were: HI=2,57+/-1,02; GHI=2,18+/
      0,81; GI=1,95+/-0,8, PI=3,9+/-1,1. In case of severe disease - HI=3,9+/-1,25,
      GHI=2,5+/-0,8, GI=2,9+/-1,2, PI=7,8+/-1,62. Clinical study has shown that
      Cholisal enables successful treatment of periodontitis. It has prolonged,
      antiinflamatory, deodorant and analgesic effect. Our investigation revealed that
      xolisale can be recommended in complex treatment of periodontal disease.

PMID- 18323592
TI  - In vitro antifungal and antileishmanial activities of steroidal saponins from
      Allium leucanthum C. Koch -- a Caucasian endemic species.
AB  - Five steroidal saponins were isolated for the first time in the flower of Allium
      leucanthum C.Koch. In vitro antifungal and antileishmanial activities of pure
      compounds as well as crude extract, spirostanoid and furostanoid fractions were
      evaluated. Spirostanol saponins (25R),5alpha- spirostan -3beta,6beta- diol 3-0
      {beta-D-glucopyranosyl-(1-->2)- 0-[beta-D-xylopyranosyl-(1-->3)]- 0-beta-D-
      glucopyranosyl -(1-->4)-beta-D- galactopyranoside } compound 3 were more
      antifungal active especially with a MCF ranging from 6,25 to 12,5 microg/ml on
      the most yeast stains tested. Spirostanol fraction was more active on amastigote
      forms of leishmania with IC(50) 0,9 microg/ml.

PMID- 18323593
TI  - [Development of the technology of the substance of davikol and standardization].
AB  - Among wide assortment of pharmaceutical remedies, that use modern medicine as a
      weapon against different diseases, special place belongs to the ophthalmic
      pharmaceutical forms, and their development presents independent branch of
      pharmaceutical technology. Recently, as a reason of various diseases and among
      them ophthalmic problems, is considered free radicals and reactions with their
      participation. Protection of the organism from such diseases presents a main goal
      of antioxidant system. Nowadays, special attention is paid to the natural
      antioxidants. On the basis of the natural honey technology of eye drops davikol
      with antioxidant activity have been developed. The objective of our study has
      been the development of the substance of prolonged pharmaceutical dosage form
      davikol - eye ophthalmic drops and its standardization. The qualitative and
      quantitative methods were developed. It is concluded that the optimal method of
      drying of davikol is sublimation. Dry powder (active substance) davikol was
      obtained; quality characteristics were identified.

PMID- 18323594
TI  - Pilot study of compliance with healthcare facility smoking laws in Georgia.
AB  - In 2003 Georgian Parliament restricted smoking in all healthcare facilities to
      designated smoking areas. Observed compliance has been low. This quantitative
      study of airborne nicotine and particulate concentrations in nine healthcare
      facilities in Tbilisi and Region Kakheti in February, 2007 was a pilot to assess
      the degree of noncompliance with the law and to identify potential strategies for
      increasing compliance. Passive sampling of nicotine and active sampling of
      PM(2.5) in selected healthcare facilities. None of the facilities we monitored
      had designated smoking areas that met the legal requirements. Fifty of the 51
      samplers registered concentrations of nicotine above the level of detection. Of
      these, 52% showed concentrations below 1 microg/m(3) nicotine, 27% showed
      concentrations between 1 and 5 microg/m(3) and 20% were above 5 microg/m(3). The
      highest nicotine levels were found in medical staff offices, and in undesignated
      "informal smoking areas". These data support qualitative observations that the
      law restricting smoking in Georgian healthcare facilities to designated areas is
      poorly enforced and does not protect patients and employees from secondhand
      smoke. These findings suggest that Georgian law should be changed to make all
      healthcare institutions smoke free environments and that there is a need for
      tobacco control programs targeted at medical professionals in Georgia.

PMID- 18323595
TI  - The intermittent and prolonged maternal separation affects behavioral reactions
      in rat pups.
AB  - The work was designed to reveal the effect of maternal deprivation on the
      behavioral reactions of rat pups during the intermittent and prolonged maternal
      separation. Research was conducted on 126 white rat pups of both sexes received
      from 26 mothers at the 1st, 15th, 21st, and 60th days after birth. All animals
      were divided into three main groups: the first group included 42 litters
      submitted to intermittent maternal deprivation (IMD). The second group included
      28 litters submitted to prolonged maternal deprivation (PMD) and 56 litters
      served as the control group. Animals were housed in a room with a controlled
      temperature, humidity, 12 h light/dark cycle, having free access to the food and
      water. The received results testify to essential influence of maternal
      deprivation on the normal functioning of CNS, revealed in the alterations of
      behaviors in rats suffering from maternal deprivation. Thus, early maternal
      separation in rat pups may serve to be the stressful stimulus for CNS and alter
      it function, which produces the behavioural disorders among them.

PMID- 18323598
TI  - A novel acetate-bound complex of human carbonic anhydrase II.
AB  - The enzyme human carbonic anhydrase II (hCAII) crystallized in an acetate-bound
      complex belonging to space group P2(1)2(1)2(1), with unit-cell parameters a =
      42.3, b = 71.8, c = 74.0 A. The structure was solved by the molecular-replacement
      method and refined to an R value of 0.18 and an R(free) of 0.21. The acetate
      molecule replaced the zinc-bound water molecule in the structure, differing from
      previous reports regarding the site of acetate binding. This mode of binding
      disrupts the hydrogen-bonded solvent network required for activity of the enzyme.
      This mode of inhibitor binding is a novel one that has not been observed
      previously.

PMID- 18323597
TI  - Structure of mouse ADP-ribosylhydrolase 3 (mARH3).
AB  - ADP-ribosylation is a reversible and covalent post-translational modification in
      which the attachment of ADP-ribose is catalyzed by ADP-ribosyltransferases and
      the removal of ADP-ribose is catalyzed by ADP-ribosylhydrolases. ADP
      ribosylhydrolase 3 from mouse, consisting of 347 amino-acid residues, has been
      cloned, purified and crystallized. The three-dimensional structure has been
      resolved at a resolution of 1.8 A. The structure constitutes a compact all-alpha
      helical protein with two Mg(2+) ions located in the active-site crevice. A
      structural comparison of mouse ADP-ribosylhydrolase 3 with its human orthologue
      shows a high degree of structural similarity. Furthermore, four prokaryotic
      proteins deposited in the PDB could be identified as being structurally related.

PMID- 18323599
TI  - Purification, crystallization and preliminary X-ray diffraction analysis of
      aspartate semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis.
AB  - Aspartate semialdehyde dehydrogenase from Mycobacterium tuberculosis (Asd, ASADH,
      Rv3708c), which is the second enzyme in the lysine/homoserine-biosynthetic
      pathways, has been expressed heterologously in Escherichia coli. The enzyme was
      purified using affinity and gel-filtration chromatographic techniques and
      crystallized in two different crystal forms. Preliminary diffraction data
      analysis suggested the presence of up to four monomers in the asymmetric unit of
      the orthorhombic crystal form A and of one or two monomers in the cubic crystal
      form B.

PMID- 18323600
TI  - Preparation, crystallization and preliminary X-ray diffraction analysis of the
      DNA-binding domain of the Ets transcription factor in complex with target DNA.
AB  - The Ets2 transcription factor is a member of the Ets transcription-factor family.
      Ets2 plays a role in the malignancy of cancer and in Down's syndrome by
      regulating the transcription of various genes. The DNA-binding domain of Ets2
      (Ets domain; ETSD), which contains residues that are highly conserved among Ets
      transcription-factor family members, was expressed as a GST-fusion protein. The
      aggregation of ETSD produced after thrombin cleavage could be prevented by
      treatment with NDSB-195 (nondetergent sulfobetaine 195). ETSD was crystallized in
      complex with DNA containing the Ets2 target sequence (GGAA) by the hanging-drop
      vapour-diffusion method. The best crystals were grown using 25% PEG 3350, 80 mM
      magnesium acetate, 50 mM sodium cacodylate pH 5.0/5.5 as the reservoir at 293 K.
      The crystals belonged to space group C2, with unit-cell parameters a = 85.89, b =
      95.52, c = 71.89 A, beta = 101.7 degrees and a V(M) value of 3.56 A(3) Da(-1).
      Diffraction data were collected to a resolution of 3.0 A.

PMID- 18323601
TI  - Crystallization and preliminary X-ray analysis of human Brn-5 transcription
      factor in complex with DNA.
AB  - The Brn-5 protein plays an important role in the control of cellular development
      and belongs to a class of transcription factors that usually contain two domains:
      the POU homeodomain (POU(HD)) and the POU-specific domain (POU(S)). Since high
      quality crystals suitable for crystallographic studies of the proteins of this
      class are difficult to obtain, all the known structural information available is
      for POU(HD) and/or POU(S). This paper describes several critical steps that
      allowed the production of high-quality crystals of the full-length Brn-5 protein
      complexed with its cognate DNA.

PMID- 18323602
TI  - Crystallization and preliminary X-ray diffraction analysis of full-length and
      proteolytically activated pyruvate oxidase from Escherichia coli.
AB  - The thiamine diphosphate- and flavin-dependent peripheral membrane enzyme
      pyruvate oxidase from Escherichia coli (EcPOX) has been crystallized in the full
      length form and as a proteolytically activated C-terminal truncation variant
      which lacks the last 23 amino acids (Delta23 EcPOX). Crystals were grown by the
      hanging-drop vapour-diffusion method using either protamine sulfate (full-length
      EcPOX) or 2-methyl-2,4-pentanediol (Delta23 EcPOX) as precipitants. Native data
      sets were collected at a X-ray home source to a resolution of 2.9 A. The two
      forms of EcPOX crystallize in different space groups. Whereas full-length EcPOX
      crystallizes in the tetragonal space group P4(3)2(1)2 with two monomers per
      asymmetric unit, the crystals of Delta23 EcPOX belong to the orthorhombic space
      group P2(1)2(1)2(1) and contain 12 monomers per asymmetric unit.

PMID- 18323603
TI  - Cloning, expression, purification, crystallization and preliminary X-ray
      diffraction analysis of variants of monoamine oxidase from Aspergillus niger.
AB  - Monoamine oxidase from Aspergillus niger (MAO-N) is an FAD-dependent enzyme that
      catalyses the conversion of terminal amines to their corresponding aldehydes.
      Variants of MAO-N produced by directed evolution have been shown to possess
      altered substrate specificity. Crystals of two of these variants (MAO-N-3 and MAO
      N-5) have been obtained; the former displays P2(1) symmetry with eight molecules
      per asymmetric unit and the latter has P4(1)2(1)2 or P4(3)2(1)2 symmetry and two
      molecules per asymmetric unit. Solution of these structures will help shed light
      on the molecular determinants of improved activity and high enantioselectivity
      towards a broad range of substrates.

PMID- 18323604
TI  - Crystallization and preliminary X-ray studies of ferredoxin-NAD(P)+ reductase
      from Chlorobium tepidum.
AB  - Ferredoxin-NAD(P)(+) reductase (FNR) is a key enzyme that catalyzes the
      photoreduction of NAD(P)(+) to generate NAD(P)H during the final step of the
      photosynthetic electron-transport chain. FNR from the green sulfur bacterium
      Chlorobium tepidum is a homodimeric enzyme with a molecular weight of 90 kDa; it
      shares a high level of amino-acid sequence identity to thioredoxin reductase
      rather than to conventional plant-type FNRs. In order to understand the
      structural basis of the ferredoxin-dependency of this unique photosynthetic FNR,
      C. tepidum FNR has been heterologously expressed, purified and crystallized in
      two forms. Form I crystals belong to space group C222(1) and contain one dimer in
      the asymmetric unit, while form II crystals belong to space group P4(1)22 or
      P4(3)22. Diffraction data were collected from a form I crystal to 2.4 A
      resolution on the synchrotron-radiation beamline NW12 at the Photon Factory.

PMID- 18323605
TI  - Crystallization and preliminary X-ray diffraction analysis of vaccinia virus H1L
      phosphatase.
AB  - The cysteine-based protein phosphatase H1L was the first reported dual
      specificity protein phosphatase. H1L is encapsidated within the vaccinia virus
      and is required for successful host infection and for the production of viable
      vaccinia progeny. H1L has therefore been proposed as a target candidate for
      antiviral compounds. Recombinant H1L has been expressed in a catalytically
      inactive form using an Escherichia coli host, leading to purification and
      crystallization by the microbatch method. The crystals diffract to 2.1 A
      resolution using synchrotron radiation. These crystals belong to space group
      P422, with unit-cell parameters a = b = 98.31, c = 169.15 A, and are likely to
      contain four molecules in the asymmetric unit. A sulfur SAD data set was
      collected to 2.8 A resolution on beamline BM14 at the ESRF to facilitate
      structure determination. Attempts to derivatize these crystals with xenon gas
      changed the space group to I422, with unit-cell parameters a = b = 63.28, c =
      169.68 A and a single molecule in the asymmetric unit. The relationship between
      these two crystal forms is discussed.

PMID- 18323606
TI  - Crystallization and preliminary X-ray crystallographic characterization of TrmFO,
      a folate-dependent tRNA methyltransferase from Thermotoga maritima.
AB  - TrmFO, previously classified as GID, is a methyltransferase that catalyzes the
      formation of 5-methyluridine or ribothymidine (T) at position 54 in tRNA in some
      Gram-positive bacteria. To date, TrmFO is the only characterized tRNA
      methyltransferase that does not use S-adenosylmethionine as the methyl-group
      donor. Instead, the donor of the methyl group is N(5),N(10)
      methylenetetrahydrofolate. The crystallization and preliminary X-ray
      crystallographic studies of TrmFO are reported here. The recombinant protein,
      cloned from Thermotoga maritima genomic DNA, was overproduced in Esherichia coli
      and crystallized in 25%(v/v) PEG 4000, 100 mM NaCl and sodium citrate buffer pH
      5.0 at 291 K using the hanging-drop vapor-diffusion method. The plate-shaped
      crystals diffracted to 2.6 A and belong to the orthorhombic space group
      P2(1)2(1)2(1), with unit-cell parameters a = 79.94, b = 92.46, c = 127.20 A.

PMID- 18323607
TI  - Crystallization and preliminary X-ray analysis of RsbS from Moorella
      thermoacetica at 2.5 A resolution.
AB  - The thermophilic bacterium Moorella thermoacetica possesses an rsb operon that is
      related to the genetic locus common to many Gram-positive bacteria that regulates
      the activity of the stress-responsive sigma factor sigma(B). One of the gene
      products of this operon is RsbS, a single STAS-domain protein that is a component
      of higher order assemblies in Bacillus subtilis known as 'stressosomes'. It is
      expected that similar complexes are found in M. thermoacetica, but in this
      instance regulating the biosynthesis of cyclic di-GMP, a ubiquitous secondary
      messenger. Selenomethionine-labelled MtRsbS protein was crystallized at room
      temperature using the hanging-drop vapour-diffusion method. Crystals belonging to
      space group P2(1)2(1)2(1), with unit-cell parameters a = 51.07, b = 60.52, c =
      89.28 A, diffracted to 2.5 A resolution on beamline I04 of the Diamond Light
      Source. The selenium substructure was solved using SHELX and it is believed that
      this represents the first reported ab initio crystal structure to be solved using
      diffraction data collected at DLS.

PMID- 18323608
TI  - Expression, purification, crystallization and preliminary X-ray diffraction
      analysis of grass carp beta2-microglobulin.
AB  - Beta(2)-microglobulin (beta(2)m) is an essential subunit of MHC I molecules; it
      stabilizes the structure of MHC I and plays a pivotal role in coreceptor
      recognition. To date, structures of beta(2)m have been solved for three different
      mammals: human, mouse and cattle. In order to illuminate the molecular
      evolutionary origin of beta2m, an understanding of its structure in lower
      vertebrates becomes important. Here, grass carp (Ctenopharyngodon idellus)
      beta(2)m (Ctid-beta(2)m) was expressed, purified and crystallized. Diffraction
      data were collected to a resolution of 2.5 A. The crystal belongs to space group
      P2(1)2(1)2(1), with unit-cell parameters a = 38.72, b = 40.65, c = 71.12 A. The
      Matthews coefficient and the solvent content were calculated to be 2.56 A Da(-1)
      and 52.07%, respectively, for one molecule per asymmetric unit. The structure has
      been solved by molecular replacement using monomeric human beta(2)m as a model.

PMID- 18323609
TI  - Purification, crystallization and preliminary X-ray analysis of the peptidoglycan
      N-acetylglucosamine deacetylase BC1960 from Bacillus cereus in the presence of
      its substrate (GlcNAc)6.
AB  - The peptidoglycan N-acetylglucosamine (GlcNAc) deacetylase BC1960 from Bacillus
      cereus (EC 3.5.1.33), an enzyme consisting of 275 amino acids, was crystallized
      in the presence of its substrate (GlcNAc)(6). The crystals belonged to the
      tetragonal space group P4(1)2(1)2, with unit-cell parameters a = b = 92.7, c =
      242.9 A and four molecules in the asymmetric unit. A complete data set was
      collected at 100 K to a resolution of 2.38 A using synchrotron radiation.

PMID- 18323610
TI  - The purification, crystallization and preliminary X-ray diffraction analysis of
      dihydrodipicolinate synthase from Clostridium botulinum.
AB  - In recent years, dihydrodipicolinate synthase (DHDPS; EC 4.2.1.52) has received
      considerable attention from both mechanistic and structural viewpoints. This
      enzyme, which is part of the diaminopimelate pathway leading to lysine, couples
      (S)-aspartate-beta-semialdehyde with pyruvate via a Schiff base to a conserved
      active-site lysine. In this paper, the expression, purification, crystallization
      and preliminary X-ray diffraction analysis of DHDPS from Clostridium botulinum,
      an important bacterial pathogen, are presented. The enzyme was crystallized in a
      number of forms, predominantly using PEG precipitants, with the best crystal
      diffracting to beyond 1.9 A resolution and displaying P4(2)2(1)2 symmetry. The
      unit-cell parameters were a = b = 92.9, c = 60.4 A. The crystal volume per
      protein weight (V(M)) was 2.07 A(3) Da(-1), with an estimated solvent content of
      41%. The structure of the enzyme will help guide the design of novel therapeutics
      against the C. botulinum pathogen.

PMID- 18323611
TI  - Crystallization and preliminary X-ray study of native and selenomethionyl beta
      1,4-mannanase AaManA from Alicyclobacillus acidocaldariusTc-12-31.
AB  - AaManA, a beta-1,4-mannanase from the thermoacidophile Alicyclobacillus
      acidocaldarius Tc-12-31, was expressed in Escherichia coli and purified in a form
      suitable for X-ray crystallographic analysis. Crystals were obtained using the
      hanging-drop vapour-diffusion method at 291 K using ammonium dihydrogen phosphate
      as a precipitant. Data were collected from native mannanase and from a
      selenomethionyl derivative to 1.90 and 1.99 A, respectively, at 100 K. The native
      crystal belongs to the orthorhombic space group P2(1)2(1)2(1), with unit-cell
      parameters a = 44.34, b = 75.55, c = 88.02 A. The derivative crystal belonged to
      the same space group as native AaManA, with unit-cell parameters a = 44.55, b =
      75.70, c = 92.66 A.

PMID- 18323612
TI  - Expression, purification, crystallization and preliminary X-ray characterization
      of two crystal forms of stationary-phase survival E protein from Campylobacter
      jejuni.
AB  - Survival E (SurE) protein from Campylobacter jejuni, a Gram-negative mesophile,
      has been overexpressed in Escherichia coli as a soluble protein, successfully
      purified and crystallized in two distinct crystal forms. The first form belongs
      to space group P2(1)2(1)2(1), with a tetramer in the asymmetric unit and unit
      cell parameters a = 80.5, b = 119.0, c = 135.3 A. The second form belongs to
      space group C2, with unit-cell parameters a = 121.4, b = 47.1, c = 97.8 A, and
      contains a dimer in the asymmetric unit. Diffraction data have been collected
      from these crystal forms to 2.5 and 2.95 A resolution, respectively.

PMID- 18323613
TI  - Crystallization and preliminary X-ray diffraction studies of polyketide synthase
      1 (PKS-1) from Cannabis sativa.
AB  - Polyketide synthase-1 (PKS-1) is a novel type III polyketide synthase that
      catalyzes the biosynthesis of hexanoyl triacetic acid lactone in Cannabis sativa
      (Mexican strain). PKS-1 was overproduced in Escherichia coli, purified and
      finally crystallized in two different space groups. The crystal obtained in 0.1 M
      HEPES buffer pH 7.5 containing 0.2 M calcium acetate and 20%(w/v) polyethylene
      glycol 3350 diffracted to 1.65 A resolution and belonged to space group P1, with
      unit-cell parameters a = 54.3, b = 59.3, c = 62.6 A, alpha = 69, beta = 81, gamma
      = 80 degrees. Another crystal obtained in 0.1 M HEPES buffer pH 7.5 containing
      0.2 M sodium chloride and 20%(w/v) polyethylene glycol 3350 diffracted to 1.55 A
      resolution and belonged to space group P2(1)2(1)2(1), with unit-cell parameters a
      = 54.3, b = 110, c = 130 A. These data will enable us to determine the crystal
      structure of PKS-1.

PMID- 18323614
TI  - Overproduction, purification and crystallization of a chondroitin sulfate A
      binding DBL domain from a Plasmodium falciparum var2csa-encoded PfEMP1 protein.
AB  - The PfEMP1 proteins of the malaria parasite Plasmodium falciparum are inserted
      into the membrane of infected red blood cells, where they mediate adhesion to a
      variety of human receptors. The DBL domains of the var2csa-encoded PfEMP1 protein
      play a critical role in malaria of pregnancy, tethering infected cells to the
      surface of the placenta through interactions with the glycosaminoglycan
      carbohydrate chondroitin sulfate A (CSA). A CSA-binding DBL domain has been
      overproduced in a bacterial expression system, purified and crystallized. Native
      data sets extending to 1.9 A resolution have been collected and phasing is under
      way.

PMID- 18323615
TI  - Expression, purification, crystallization and preliminary X-ray analysis of the
      polysaccharide lyase RB5312 from the marine planctomycete Rhodopirellula baltica.
AB  - Polysaccharide lyases belonging to family PL1 act on pectins. These anionic
      polymers are usually produced by terrestrial plants and therefore pectinolytic
      enzymes are not frequently observed in marine microorganisms. The protein RB5312
      from the marine bacterium Rhodopirellula baltica is distantly related to family
      PL1 pectate lyases, but its exact function is unclear. In this study, the
      expression and purification of a recombinant form of RB5312 are described. This
      protein was crystallized using the hanging-drop vapour-diffusion method. The
      crystals belongs to space group P2(1)2(1)2(1), with unit-cell parameters a =
      39.05, b = 144.05, c = 153.97 A, alpha = beta = gamma = 90 degrees. A complete
      data set was collected to 1.8 A resolution from a native crystal.

PMID- 18323616
TI  - Crystallization and preliminary X-ray crystallographic analysis of rabbit L
      gulonate 3-dehydrogenase.
AB  - Rabbit L-gulonate 3-dehydrogenase was crystallized using the oil-microbatch
      method at 295 K. X-ray diffraction data were collected to 1.70 A resolution from
      a crystal at 100 K using synchrotron radiation. The crystal belongs to the C
      centred monoclinic space group C2, with unit-cell parameters a = 71.81, b =
      69.08, c = 65.64 A, beta = 102.7 degrees. Assuming the presence of a monomeric
      protomer in the asymmetric unit gives a V(M) value of 2.21 A(3) Da(-1) and a
      solvent content of 44.4%. A cocrystal with NADH, which was isomorphous to the apo
      form, was also prepared and diffraction data were collected to 1.85 A resolution
      using Cu Kalpha radiation at 100 K.

PMID- 18323617
TI  - Modulation of activity by Arg407: structure of a fungal alpha-1,2-mannosidase in
      complex with a substrate analogue.
AB  - Class I alpha-mannosidases (glycoside hydrolase family GH47) play key roles in
      the maturation of N-glycans and the ER-associated degradation of unfolded
      glycoproteins. The 1.95 A resolution structure of a fungal alpha-1,2-mannosidase
      in complex with the substrate analogue methyl-alpha-D-lyxopyranosyl-(1',2)-alpha
      D-mannopyranoside (LM) shows the intact disaccharide spanning the -1/+1 subsites,
      with the D-lyxoside ring in the -1 subsite in the 1C4 chair conformation, and
      provides insight into the mechanism of catalysis. The absence of the C5'
      hydroxymethyl group on the D-lyxoside moiety results in the side chain of Arg407
      adopting two alternative conformations: the minor one interacting with Asp375 and
      the major one interacting with both the D-lyxoside and the catalytic base Glu409,
      thus disrupting its function. Chemical modification of Asp375 has previously been
      shown to inactivate the enzyme. Taken together, the data suggest that Arg407,
      which belongs to the conserved sequence motif RPExxE, may act to modulate the
      activity of the enzyme. The proposed mechanism for modulating the activity is
      potentially a general mechanism for this superfamily.

PMID- 18323618
TI  - Application of maximum-entropy maps in the accurate refinement of a putative
      acylphosphatase using 1.3 A X-ray diffraction data.
AB  - Accurate structural refinement of a putative acylphosphatase using 1.3 A X-ray
      diffraction data was carried out using charge densities determined by the maximum
      entropy method (MEM). The MEM charge density clearly revealed detailed features
      of the solvent region of the putative acylphosphatase crystalline structure, some
      of which had never been observed in conventional Fourier maps. The structural
      model in the solvent region was constructed as distributions of anisotropic water
      atoms. The omit-difference MEM maps and the difference MEM maps were effective in
      revealing details of the protein structure, such as multiple conformations of the
      side chains of amino-acid residues, anisotropy of atoms and H atoms. By model
      building using the MEM charge densities, the reliability factors R1 and R free in
      the SHELX refinement were dramatically improved from 17.9% and 18.3% to 9.6% and
      10.0%, respectively. The present results prove the usefulness of MEM in improving
      the accuracy of refinement of protein crystal structures.

PMID- 18323619
TI  - Three-dimensional structures of L-asparaginase from Erwinia carotovora complexed
      with aspartate and glutamate.
AB  - The crystal structures of Erwinia carotovora L-asparaginase complexed with L
      aspartate and L-glutamate were determined at 1.9 and 2.2 A, respectively, using
      the molecular-replacement method and were refined to R factors of about 21% in
      both cases. The positions of the ligands in the active site were located. A
      comparison of the new structures with the known structures of Escherichia coli L
      asparaginase and Er. chrysanthemi L-asparaginase was performed. It was found that
      the arrangement of the ligands practically coincides in all three enzymes. The
      peculiarities of the quaternary structure of the enzyme, the possible role of
      water molecules in the enzyme action and the conformational changes during the
      catalyzed reaction are discussed.

PMID- 18323620
TI  - Metals in proteins: correlation between the metal-ion type, coordination number
      and the amino-acid residues involved in the coordination.
AB  - Metal ions are constituents of many metalloproteins, in which they have either
      catalytic (metalloenzymes) or structural functions. In this work, the
      characteristics of various metals were studied (Cu, Zn, Mg, Mn, Fe, Co, Ni, Cd
      and Ca in proteins with known crystal structure) as well as the specificity of
      their environments. The analysis was performed on two data sets: the set of
      protein structures in the Protein Data Bank (PDB) determined with resolution <1.5
      A and the set of nonredundant protein structures from the PDB. The former was
      used to determine the distances between each metal ion and its electron donors
      and the latter was used to assess the preferred coordination numbers and common
      combinations of amino-acid residues in the neighbourhood of each metal. Although
      the metal ions considered predominantly had a valence of two, their preferred
      coordination number and the type of amino-acid residues that participate in the
      coordination differed significantly from one metal ion to the next. This study
      concentrates on finding the specificities of a metal-ion environment, namely the
      distribution of coordination numbers and the amino-acid residue types that
      frequently take part in coordination. Furthermore, the correlation between the
      coordination number and the occurrence of certain amino-acid residues (quartets
      and triplets) in a metal-ion coordination sphere was analysed. The results
      obtained are of particular value for the identification and modelling of metal
      binding sites in protein structures derived by homology modelling. Knowledge of
      the geometry and characteristics of the metal-binding sites in metalloproteins of
      known function can help to more closely determine the biological activity of
      proteins of unknown function and to aid in design of proteins with specific
      affinity for certain metals.

PMID- 18323621
TI  - Differential specific radiation damage in the Cu II-bound and Pd II-bound forms
      of an alpha-helical foldamer: a case study of crystallographic phasing by RIP and
      SAD.
AB  - The high photon flux at third-generation synchrotron sources can inflict
      significant primary radiation damage upon macromolecular crystals, even when the
      crystals are cryocooled. However, specific radiation-induced structural changes
      can be exploited for de novo phasing by an approach known as radiation damage
      induced phasing (RIP). Here, RIP and single-wavelength anomalous dispersion (SAD)
      phasing were alternatively used to derive experimental phases to 1.2 A resolution
      for crystals of an alpha-helical 18-residue peptide, MINTS, which was derived
      from the neurotoxin apamin and the palladium-bound structure of which is now
      reported. Helix formation is induced by the binding of palladium (or copper) to
      two histidines spaced four residues apart, while two disulfide bonds tether the N
      terminal helix to the C-terminal loop-like part of the peptide. Either RIP or SAD
      phasing of the palladium-bound and copper-bound forms of MINTS, which
      crystallized in different space groups, resulted in density maps of superb
      quality. Surprisingly, RIP phasing of the metal-bound complex structures of MINTS
      was a consequence of differential radiation damage, resting primarily on the
      reduction of the disulfide bonds in Pd-MINTS and on depletion of the metal sites
      in Cu-MINTS. Its miniprotein-like characteristics, versatile metal-binding
      properties and ease of crystallization suggest MINTS to be a convenient test
      specimen for methods development in crystallographic phasing based on either
      synchrotron or in-house X-ray diffraction data.

PMID- 18323622
TI  - Structure of human monocyte chemoattractant protein 4 (MCP-4/CCL13).
AB  - Monocyte chemoattractant proteins (MCPs) belong to the CC chemokine family and
      are involved in many (patho)physiological processes characterized by mononuclear
      cell infiltration, including tissue remodeling, atherosclerosis and cancer
      metastasis. Here, the crystal structure of human monocyte chemoattractant protein
      4 (MCP-4) refined at 1.70 A resolution is reported with crystallographic values R
      = 0.180 and R free = 0.212. The overall MCP-4 fold reveals the typical tertiary
      features of the CC chemokine family. A central three-stranded antiparallel beta
      sheet is C-terminally flanked by an overlaying alpha-helix, while the N-terminal
      part of the molecule forms an extended loop that is anchored to the rest of the
      molecule via two disulfide bridges, Cys11-Cys35 and Cys12-Cys51. The crystal
      packing suggests the existence of MCP-4 dimers with a dimerization interface
      similar to those previously reported for the X-ray structures of MCP-1 and MCP-2.

PMID- 18323623
TI  - Structure of human argininosuccinate synthetase.
AB  - Argininosuccinate synthetase catalyzes the transformation of citrulline and
      aspartate into argininosuccinate and pyrophosphate using the hydrolysis of ATP to
      AMP and pyrophosphate. This enzymatic process constitutes the rate-limiting step
      in both the urea and arginine-citrulline cycles. Previous studies have
      investigated the crystal structures of argininosuccinate synthetase from
      bacterial species. In this work, the first crystal structure of human
      argininosuccinate synthetase in complex with the substrates citrulline and
      aspartate is presented. The human enzyme is compared with structures of
      argininosuccinate synthetase from bacteria. In addition, the structure also
      provides new insights into the function of the numerous clinical mutations
      identified in patients with type I citrullinaemia (also known as classic
      citrullinaemia).

PMID- 18323624
TI  - Glycerol concentrations required for the successful vitrification of cocktail
      conditions in a high-throughput crystallization screen.
AB  - The Hauptman-Woodward Medical Research Institute runs a high-throughput
      crystallization screening service in which macromolecules are screened against
      1536 potential crystallization cocktails. Typically, multiple crystallization
      leads are identified. With a limited amount of sample, the question becomes ;How
      many leads can be optimized and which leads are most likely to produce X-ray
      diffraction data?'. In order to prioritize the hits for optimization, the amount
      of glycerol required to successfully cryocool each cocktail has been determined
      for the cocktails used in the high-throughput screen. Those hit conditions that
      require the minimum amount of cryoprotectant for successful vitrification will be
      closer in chemical make-up to the mother liquor. Hence, if the physical
      properties of the crystals are similar, one could logically prioritize leads that
      are more likely to produce diffraction based upon the chemical similarity of the
      native to the cryopreserved mother liquor.

PMID- 18323625
TI  - Critical importance of loop conformation to avidin-enhanced hydrolysis of an
      active biotin ester.
AB  - The homotetrameric and biotin-binding properties of avidin and streptavidin have
      been exploited for a myriad of biotechnological applications and theoretical
      studies. Among the few differences between the two proteins is the capacity of
      avidin to hydrolyze biotinyl p-nitrophenyl ester (BNP), as opposed to
      streptavidin, which fully protects the same pseudosubstrate from hydrolysis.
      Combined mutagenesis and X-ray analysis have been used to attempt to understand
      this diametric difference in activities. It was found that a charged residue and
      one of the loops (L3,4) are together responsible for this difference. Recently,
      the avidin-related analogue AVR4 was found to have an even more pronounced BNP
      hydrolysis activity than avidin. Again, the combination of charged residue(s)
      (Asp39 and/or Arg112) and the rigid conformation of the L3,4 loop was suggested
      to be responsible for the observed hydrolysis reaction. However, replacement of
      the latter charged residues in AVR4 resulted in only a modest reduction in
      hydrolytic activity at most, whereas replacement of the L3,4 loop of avidin with
      the rigid loop of AVR4 caused a dramatic increase in the activity of avidin.
      These results clearly demonstrate that the main feature responsible for the
      observed differences in rates of hydrolysis among the avidins is the
      conformational status of the L3,4 loop, which imposes conformational constraints
      on the pseudosubstrate, thereby rendering it susceptible to nucleophilic attack
      by solvent. In this context, the hydrolytic properties of the avidins reflect
      enzyme catalysis, in that subtleties in substrate binding are the determining
      features of catalytic efficiency.

PMID- 18323626
TI  - Crystal packing of plant-type L-asparaginase from Escherichia coli.
AB  - Plant-type L-asparaginases hydrolyze the side-chain amide bond of L-asparagine or
      its beta-peptides. They belong to the N-terminal nucleophile (Ntn) hydrolases and
      are synthesized as inactive precursor molecules. Activation occurs via the
      autoproteolytic release of two subunits, alpha and beta, the latter of which
      carries the nucleophile at its N-terminus. Crystallographic studies of plant-type
      asparaginases have focused on an Escherichia coli homologue (EcAIII), which has
      been crystallized in several crystal forms. Although they all belong to the same
      P2 1 2 1 2 1 space group with similar unit-cell parameters, they display
      different crystal-packing arrangements and thus should be classified as separate
      polymorphs. This variability stems mainly from different positions of the EcAIII
      molecules within the unit cell, although they also exhibit slight differences in
      orientation. The intermolecular interactions that trigger different crystal
      lattice formation are mediated by ions, which represent the most variable
      component of the crystallization conditions. This behaviour confirms recent
      observations that small molecules might promote protein crystal lattice
      formation.

PMID- 18323627
TI  - The structure of a redundant enzyme: a second isoform of aspartate beta
      semialdehyde dehydrogenase in Vibrio cholerae.
AB  - Aspartate-beta-semialdehyde dehydrogenase (ASADH) is an essential enzyme that is
      found in bacteria, fungi and plants but not in humans. ASADH produces the first
      branch-point metabolite in the biosynthetic pathways that lead to the production
      of lysine, threonine, methionine and isoleucine as well as the cell-wall
      precursor diaminopimelate. As a consequence, ASADH appears to be an excellent
      target for the development of novel antibiotics, especially for Gram-negative
      bacteria that require diaminopimelate for cell-wall biosynthesis. In contrast to
      the Gram-negative ASADHs, which readily formed well diffracting crystals, the
      second isoform of aspartate-beta-semialdehyde dehydrogenase from Vibrio cholerae
      (vcASADH2) was less well behaved in initial crystallization trials. In order to
      obtain good-quality single crystals of vcASADH2, a buffer-optimization protocol
      was used in which the initial purification buffer was exchanged into a new
      condition derived from a pre-crystalline hit. The unliganded structure of
      vcASADH2 has been determined to 2.2 A resolution to provide additional insight
      into the structural and functional evolution of the ASADH enzyme family. The
      overall fold and domain organization of this new structure is similar to the Gram
      negative, Gram-positive and archeal ASADH structures determined previously,
      despite having less than 50% sequence identity to any of these family members.
      The substrate-complex structure reveals that the binding of L-aspartate-beta
      semialdehyde (ASA) to vcASADH2 is accommodated by structural changes in the amino
      acid binding site and in the helical subdomain that is involved in the dimer
      interface. Structural alignments show that this second isoform from Gram-negative
      V. cholerae most closely resembles the ASADH from a Gram-positive organism and is
      likely to bind the coenzyme in a different conformation to that observed in the
      other V. cholerae isoform.

PMID- 18323628
TI  - Structures of D-amino-acid amidase complexed with L-phenylalanine and with L
      phenylalanine amide: insight into the D-stereospecificity of D-amino-acid amidase
      from Ochrobactrum anthropi SV3.
AB  - The crystal structures of D-amino-acid amidase (DAA) from Ochrobactrum anthropi
      SV3 in complex with L-phenylalanine and with L-phenylalanine amide were
      determined at 2.3 and 2.2 A resolution, respectively. Comparison of the L
      phenylalanine amide complex with the D-phenylalanine complex reveals that the D
      stereospecificity of DAA might be achieved as a consequence of three structural
      factors: (i) the hydrophobic cavity in the region in which the hydrophobic side
      chain of the substrate is held, (ii) the spatial arrangement of Gln310 O and
      Glu114 O epsilon2 that fixes the amino N atom of the substrate and (iii) the
      existence of two cavities that keep the carboxyl/amide group of the substrate
      near or apart from Ser60 O gamma.

PMID- 18323629
TI  - A forward-looking suggestion for resolving the stereochemical restraints debate:
      ideal geometry functions.

PMID- 18323630
TI  - Chemical structure of posttranslational modification with a farnesyl group on
      tryptophan.
AB  - Bacillus subtilis and related bacilli produce a posttranslationally modified
      oligopeptide, the ComX pheromone, that stimulates natural genetic competence
      controlled by quorum sensing. The ComX(RO-C-2) pheromone from strain RO-C-2 must
      be modified with a farnesyl group on the Trp residue, but the precise structure
      is not known. Here we report the precise nature of posttranslational
      farnesylation of ComX(RO-C-2) pheromone on the Trp residue, resulting in the
      formation of a tricyclic structure. The ComX(168) pheromone, produced by the
      standard laboratory strain used in the study of B. subtilis, is also
      posttranslationally farnesylated according to phylogenetic resemblance.

PMID- 18323631
TI  - Specific discrimination of chicken DNA from other poultry DNA in processed foods
      using the polymerase chain reaction.
AB  - In the present study, specific discrimination of chicken DNA contamination in
      processed foods using the polymerase chain reaction was investigated. The primer
      pair was designed to amplify a 102-bp fragment of the chicken mitochondrial 16S
      ribosomal RNA gene. While the DNA from chicken meat was amplified, the DNA from
      other poultry meat, mammalian meat, fish, shellfish, and cereals was not
      amplified. The primer amplified DNA fragments derived from model processed and
      nonprocessed food samples containing 0.001, 0.01, 0.1, 1, 10, and 100% chicken.

PMID- 18323632
TI  - Hypoglycemic activity of Eriobotrya japonica seeds in type 2 diabetic rats and
      mice.
AB  - The hypoglycemic effects of Eriobotrya japonica seeds were investigated in type 2
      diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and KK-A(y) mice. The
      rats and mice were fed on a diet containing 10% powdered Eriobotrya japonica
      seeds with the coat intact for 4 months. Although the blood glucose concentration
      in the OLETF rats fed on the control diet without Eriobotrya japonica seeds was
      increased with time, the concentration in the OLETF rats fed on the diet with
      Eriobotrya japonica seeds was consistently low throughout the experimental period
      and was comparable to the level in Long-Evans Tokushima Otsuka (LETO) rats which
      are normal non-diabetic rats. Serum insulin was significantly lower in the OLETF
      rats fed on the Eriobotrya japonica seed diet than in those fed on the control
      diet at the termination of the experimental period. Eriobotrya japonica seeds
      suppressed the increment of blood glucose for 4 months and also effectively
      improved the glucose tolerance in the KK-A(y) mice, these actions being mainly
      exerted by the ethanol extract of the seeds. These results suggest that
      Eriobotrya japonica seeds had a hypoglycemic property and the effect is
      attributable to the components extracted by ethanol.

PMID- 18323633
TI  - Elicitor and calatalse activity of conidia suspensions of various strains of
      Magnaporthe grisea in suspension-cultured cells of rice.
AB  - A conidia suspension of Magnaporthe grisea carried elicitor activity that induced
      the expression of defense-related genes and the production of H(2)O(2) in
      suspension-cultured rice cells. The levels of H(2)O(2) produced were dependent on
      fungal isolates and were correlated with the catalase activity in the supernatant
      fraction of each conidia suspension, not with gene-for-gene interactions.

PMID- 18323634
TI  - Mouse AKR1E1 is an ortholog of pig liver NADPH dependent 1,5-anhydro-D-fructose
      reductase.
AB  - In many organisms, glycogen gives rise to 1,5-anhydro-D-fructose (AF), which is
      reduced to 1,5-anhydro-D-glucitol (AG). AF reductase, which catalyzes the latter
      reaction, was purified from pig liver, but mouse ortholog has not yet been
      reported. In the database, aldo-keto reductase family 1, member E1 (AKR1E1)
      showed highest homology to pig enzyme. We confirmed that cloned AKR1E1 is mouse
      ortholog based on enzymatic properties of purified recombinant protein.

PMID- 18323635
TI  - Effects of cellulose crystallinity, hemicellulose, and lignin on the enzymatic
      hydrolysis of Miscanthus sinensis to monosaccharides.
AB  - The effects of cellulose crystallinity, hemicellulose, and lignin on the
      enzymatic hydrolysis of Miscanthus sinensis to monosaccharides were investigated.
      A air-dried biomass was ground by ball-milling, and the powder was separated into
      four fractions by passage through a series of sieves with mesh sizes 250-355
      microm, 150-250 microm, 63-150 microm, and <63 microm. Each fraction was
      hydrolyzed with commercially available cellulase and beta-glucosidase. The yield
      of monosaccharides increased as the crystallinity of the substrate decreased. The
      addition of xylanase increased the yield of both pentoses and glucose.
      Delignification by the sodium chlorite method improved the initial rate of
      hydrolysis by cellulolytic enzymes significantly, resulting in a higher yield of
      monosaccharides as compared with that for untreated samples. When delignified M.
      sinensis was hydrolyzed with cellulase, beta-glucosidase, and xylanase,
      hemicellulose was hydrolyzed completely into monosaccharides, and the conversion
      rate of glucan to glucose was 90.6%.

PMID- 18323636
TI  - Application of several molecular techniques to study numerically predominant
      Bifidobacterium spp. and Bacteroidales order strains in the feces of healthy
      children.
AB  - Bifidobacteria and Bacteroides-like bacteria are strictly anaerobic nonpathogenic
      members of human intestinal microflora. Here we describe an analysis of the
      species and subspecies composition of these bacterial populations in healthy
      children using a combination of culture and molecular methods at two different
      time points. It was found that B. bifidum and B. longum are the most common
      dominant taxons in infants aged between 8 and 16 months. The majority of the
      infants carried several dominant Bifidobacterium strains belonging to different
      species. Examination of the dominant bifidoflora in some of these children after
      a 5-year period showed major shifts in both species and strain composition, but
      the dominant strains remained unchanged in two children. The majority of dominant
      Bacteroides-like isolates belonged to species B. vulgatus and B. uniformis, but
      members of genera Alistipes and Barnesiella were common too. In addition, a novel
      approach to species identification of Bacteroidales order bacteria using
      amplified ribosomal DNA restriction analysis (ARDRA) is described.

PMID- 18323637
TI  - Kinetic studies of Micrococcus luteus B-P 26 undecaprenyl diphosphate synthase
      reaction using 3-desmethyl allylic substrate analogs.
AB  - In order to investigate the substrate binding feature of undecaprenyl diphosphate
      synthase from Micrococcus luteus B-P 26 with respect to farnesyl diphosphate and
      a reaction intermediate, (Z,E,E)-geranylgeranyl diphosphate, we examined the
      reactivity of artificial substrate analogs, 3-desmethyl farnesyl diphosphate and
      3-desmethyl Z-geranylgeranyl diphosphate, which lack the methyl group at the 3
      position of farnesyl diphosphate and Z-geranylgeranyl diphosphate, respectively.
      Undecaprenyl diphosphate synthase did not accept either of the 3-desmethyl
      analogs as the allylic substrate, indicating that the methyl group at the 3
      position of the allylic substrate is important in the undecaprenyl diphosphate
      synthase reaction. These analogs showed different inhibition patterns in the cis
      prenyl chain elongation reaction with respect to the reactions of farnesyl
      diphosphate and Z-geranylgeranyl diphosphate as allylic substrate. These results
      suggest that the binding site for the natural substrate farnesyl diphosphate and
      those for the intermediate allylic diphosphate, which contains the cis-prenyl
      unit, are different during the cis-prenyl chain elongation reaction.

PMID- 18323638
TI  - In vivo and in vitro complementation study comparing the function of DnaK
      chaperone systems from halophilic lactic acid bacterium Tetragenococcus
      halophilus and Escherichia coli.
AB  - In this study, we characterized the DnaK chaperone system from Tetragenococcus
      halophilus, a halophilic lactic acid bacterium. An in vivo complementation test
      showed that under heat stress conditions, T. halophilus DnaK did not rescue the
      growth of the Escherichia coli dnaK deletion mutant, whereas T. halophilus DnaJ
      and GrpE complemented the corresponding mutations of E. coli. Purified T.
      halophilus DnaK showed intrinsic weak ATPase activity and holding chaperone
      activity in vitro, but T. halophilus DnaK did not cooperate with the purified
      DnaJ and GrpE from either T. halophilus or E. coli in ATP hydrolysis or
      luciferase-refolding reactions under the conditions tested. E. coli DnaK,
      however, cross-reacted with those from both bacteria. This difference in the
      cooperation with DnaJ and GrpE appears to result in an inability of T. halophilus
      DnaK to replace the in vivo function of the DnaK chaperone of E. coli.

PMID- 18323639
TI  - Substrate specificities of porcine and bovine enteropeptidases toward the peptide
      Val-(Asp)4-Lys-Ile-Val-Gly and its analogs.
AB  - The substrate specificities of porcine and bovine enteropeptidases were
      investigated using the peptide Val-(Asp)(4)-Lys-Ile-Val-Gly and its various
      analogs with mutations in the (Asp)(4)-Lys sequence as substrates. The results
      indicated that in addition to P1 Lys, P2 Asp in the substrates is most important,
      that P3 Asp is additionally important, and that P5 Asp contributes somewhat to
      the susceptibility, and that P4 Asp is the least important. These results were
      essentially identical as between porcine and bovine enteropeptidases.

PMID- 18323640
TI  - Comparison of the preventive activity of isorhamnetin glycosides from atsumi-kabu
      (red turnip, Brassica, campestris L.) leaves on carbon tetrachloride-induced
      liver injury in mice.
AB  - Isorhamnetin 3-O-glucoside, which was contained together with isorhamnetin 3,7-di
      O-glucoside in atsumi-kabu leaves, suppressed increases in the plasma ALT and AST
      activities of mice with liver injury induced by the injection of carbon
      tetrachloride, but no suppression by isorhamnetin 3,7-di-O-glucoside was
      apparent. This result indicates that the release of glucose at the 7-position in
      isorhamnetin 3,7-di-O-glucoside was very important to mitigating liver injury.

PMID- 18323641
TI  - Chlorogenic acid and its metabolite m-coumaric acid evoke neurite outgrowth in
      hippocampal neuronal cells.
AB  - We evaluated the neurotrophic activity of dietary polyphenols by using primary
      cultures of fetal rat hippocampal neurons in a serum-free medium. Among the
      tested compounds, chlorogenic acid and its metabolite, m-coumaric acid, together
      with catechins and flavanone, were found to promote neuronal differentiation
      comparable to the phytochemical, honokiol, which has been reported to show potent
      neurotrophic activity. The present findings may contribute to the development of
      further neurotrophic studies on dietary polyphenols and their metabolites.

PMID- 18323642
TI  - Purification and characterization of a carbohydrate: acceptor oxidoreductase from
      Paraconiothyrium sp. that produces lactobionic acid efficiently.
AB  - A carbohydrate:acceptor oxidoreductase from Paraconiothyrium sp. was purified and
      characterized. The enzyme efficiently oxidized beta-(1-->4) linked sugars, such
      as lactose, xylobiose, and cellooligosaccharides. The enzyme also oxidized
      maltooligosaccharides, D-glucose, D-xylose, D-galactose, L-arabinose, and 6-deoxy
      D-glucose. It specifically oxidized the beta-anomer of lactose. Molecular oxygen
      and 2,6-dichlorophenol indophenol were reduced by the enzyme as electron
      acceptors. The Paraconiothyrium enzyme was identified as a carbohydrate:acceptor
      oxidoreductase according to its specificity for electron donors and acceptors,
      and its molecular properties, as well as the N-terminal amino acid sequence.
      Further comparison of the amino acid sequences of lactose oxidizing enzymes
      indicated that carbohydrate:acceptor oxidoreductases belong to the same group as
      glucooligosaccharide oxidase, while they differ from cellobiose dehydrogenases
      and cellobiose:quinone oxidoreductases.

PMID- 18323643
TI  - Distinct physiological roles of two membrane-bound dehydrogenases responsible for
      D-sorbitol oxidation in Gluconobacter frateurii.
AB  - Two different membrane-bound enzymes oxidizing D-sorbitol are found in
      Gluconobacter frateurii THD32: pyroloquinoline quinone-dependent glycerol
      dehydrogenase (PQQ-GLDH) and FAD-dependent D-sorbitol dehydrogenase (FAD-SLDH).
      In this study, FAD-SLDH appeared to be induced by L-sorbose. A mutant defective
      in both enzymes grew as well as the wild-type strain did, indicating that both
      enzymes are dispensable for growth on D-sorbitol. The strain defective in PQQ
      GLDH exhibited delayed L-sorbose production, and lower accumulation of it,
      corresponding to decreased oxidase activity for D-sorbitol in spite of high D
      sorbitol dehydrogenase activity, was observed. In the mutant strain defective in
      PQQ-GLDH, oxidase activity with D-sorbitol was much more resistant to cyanide,
      and the H(+)/O ratio was lower than in either the wild-type strain or the mutant
      strain defective in FAD-SLDH. These results suggest that PQQ-GLDH connects
      efficiently to cytochrome bo(3) terminal oxidase and that it plays a major role
      in L-sorbose production. On the other hand, FAD-SLDH linked preferably to the
      cyanide-insensitive terminal oxidase, CIO.

PMID- 18323644
TI  - Differences in concentrations of acetyl-CoA and malonyl-CoA in shoots and roots
      of Zea mays.
AB  - We measured the concentrations of acetyl-CoA and malonyl-CoA in shoots and roots
      of corn (Zea mays, L., cv. "Peter Corn"). Acetyl-CoA and malonyl-CoA
      concentrations were found to be relatively constant in shoots and in roots under
      a light-dark cycle. Acetyl-CoA concentrations were lower in shoots than in roots,
      whereas malonyl-CoA concentrations were higher in shoots than in roots.

PMID- 18323645
TI  - Purification and gene cloning of a dehydrogenase from Lactobacillus brevis that
      catalyzes a reaction involved in aflatoxin biosynthesis.
AB  - When 10 strains of lactic acid bacteria were incubated with 5'-hydroxyaverantin
      (HAVN), a precursor of aflatoxins, seven of them converted HAVN to averufin; the
      same reaction is found in aflatoxin biosynthesis of aflatoxigenic fungi. These
      bacteria had a dehydrogenase that catalyzed the reaction from HAVN to 5'
      oxoaverantin (OAVN), which was so unstable that it was easily converted to
      averufin. The enzyme was purified from Lactobacillus brevis IFO 12005. The
      molecular mass of the enzyme was 100 kDa on gel filtration chromatography and 33
      kDa on SDS polyacrylamide gel electrophoresis (SDS-PAGE). The gene encoding the
      enzyme was cloned and sequenced. The deduced protein consisted of 249 amino
      acids, and its estimated molecular mass was 25,873, in agreement with that by
      time of flight mass spectrometry (TOF MS) analysis. Although the deduced amino
      acid sequence showed about 50% identity to those reported for alcohol
      dehydrogenases from L. brevis or L. kefir, the commercially available alcohol
      dehydrogenase from L. kefir did not convert HAVN to OAVN. Aspergillus parasiticus
      HAVN dehydrogenase showed about 25% identity in amino acid sequence with the
      dehydrogenase and also with these two alcohol dehydrogenases.

PMID- 18323646
TI  - Purification and characterization of a rice class I chitinase, OsChia1b, produced
      in Esherichia coli.
AB  - To determine the properties and structure of OsChia1b, a family 19 chitinase from
      Oryza sativa L. cv. Nipponbare (japonica ssp.), recombinant OsChia1b was produced
      in Esherichia coli cells and purified to homogeneity by chitin affinity column
      chromatography. OsChia1b was highly active against soluble chitinous substrate,
      but not against crystalline chitin, and clearly inhibited hyphal extension of
      Trichoderma reesei.

PMID- 18323647
TI  - Yeast glycobiology and its application.
AB  - In this review, I describe the yeast glycans and their biosynthetic pathways,
      especially in the budding yeast Saccharomyces cerevisiae. The biosynthetic
      pathway of N-glycan in the endoplasmic reticulum is similar to that of mammalian
      cells, while the pathway in the Golgi is different from that of mammalian cells,
      but the biosynthetic pathway of O-glycan, mainly composed of O-oligomannoses,
      appears to be specific to yeast cells. Yeast systems are useful not only to
      understand the basic mechanisms of glycan synthesis but also to produce
      therapeutic proteins with human-type glycans. Protein modification by
      glycosylphosphatidylinositol is one of the major post-translational modifications
      in which oligosaccharides are involved. The biosynthetic pathway and the
      physiological function of glycosylphosphatidylinositol in S. cerevisiae are
      described in relation to lipid microdomains (also called "lipid rafts"), focusing
      on the latest findings related to lipid remodeling of GPI-anchored proteins.

PMID- 18323648
TI  - Thermodynamic redox properties governing the half-reduction characteristics of
      histamine dehydrogenase from Nocardioides simplex.
AB  - Histamine dehydrogenase from Nocardioides simplex is a homodimer and belongs to
      the family of iron-sulfur flavoproteins having one [4Fe-4S] cluster and one 6-S
      cysteinyl FMN per monomer. In the reductive titration with histamine, two
      electron reduction occurred per monomer at pH<9, while single-electron reduction
      proceeded at pH>9. The substrate-reduced histamine dehydrogenase yielded an
      electron paramagnetic resonance spectral signal assigned to the flavin
      semiquinone. The signal intensity increased with pH up to pH 9 and reached a
      maximum at pH>9. These unique features are explained in terms of the redox
      potential of the cofactors, where the redox potential was evaluated over a pH
      range from 7 to 10 by using a spectroelectrochemical titration method for the
      flavin and cyclic voltammetry for the [4Fe-4S] cluster. The bell-type pH
      dependence of the enzymatic activity is also discussed in terms of the pH
      dependence of the centers' redox potential.

PMID- 18323649
TI  - Isolation and characterization of pectin from peel of Citrus tankan.
AB  - A pectin was extracted from the peel of Citrus tankan with a yield of 2.75%. The
      uronic acid content was 80.0%, and the degree of methoxylation was 63.2%. The
      pectin was composed of D-GalA, D-Gal, L-Ara and L-Rha in the molar ratio of
      100:11.3:3.6:2.6. The molecular weight was estimated to be approximately 9.2 x
      10(4). The pectin formed a gel by conventional procedures.

PMID- 18323650
TI  - Determination of antihypertensive peptides from an izumi shrimp hydrolysate.
AB  - The izumi shrimp (Plesionika izumiae Omori, 1971) is an unused resource which can
      be caught off the southern coast of Tokushima Prefecture. We have previously
      found that an izumi shrimp hydrolysate significantly inhibited the age-associated
      spontaneous increase in blood pressure in stroke-prone spontaneously hypertensive
      rats. In this present study, two angiotensin I-converting enzyme inhibitory
      peptides were isolated from an izumi shrimp hydrolysate by using high-performance
      liquid chromatography, and their amino acid sequences were determined to be Val
      Trp-Tyr-His-Thr and Val-Trp. A single oral administration of synthetic Val-Trp
      Tyr-His-Thr or Val-Trp significantly decreased the blood pressure in stroke-prone
      spontaneously hypertensive rats. The antigenicity and allergenicity of the izumi
      shrimp hydrolysate against BALB/c mice were very low. These results demonstrate
      that the angiotensin I-converting enzyme inhibitory peptides isolated from the
      izumi shrimp hydrolysate had an anti-hypertensive effect on rats.

PMID- 18323651
TI  - Effects of a Dictamnus dasycarpus T. extract on allergic models in mice.
AB  - The anti-allergic effect of a 70% ethanol extract from Dictamnus dasycarpus Turcz
      (DDT) was studied in mice. DDT at doses of 200 and 500 mg/kg inhibited the
      systemic anaphylactic shock induced by compound 48/80 in a dose-dependent manner.
      It also inhibited dose-dependently the scratching behavior induced by compound
      48/80, histamine and serotonin. An increase in the vascular permeability induced
      by compound 48/80, histamine and serotonin was also inhibited by DDT. In an in
      vitro study, DDT inhibited the histamine released from rat peritoneal mast cells
      induced by compound 48/80. It seems likely from these findings that DDT was
      effective in antagonizing certain pharmacological effects induced by compound
      48/80 that occurred via both histamine and serotonin released from mast cells. In
      conclusion, DDT may be effective in the relief of symptoms of allergic atopic
      dermatitis and other allergy-related diseases.

PMID- 18323652
TI  - Analysis of food allergen structures and development of foods for allergic
      patients.
AB  - Food allergy is one of the important health problems, and countermeasures are
      socially required. We have been undertaking studies on wheat allergens and their
      epitopes, and have developed a method for producing hypoallergenic wheat flour by
      enzymatic modification. The hypoallergenic products are now provided to patients.
      More noteworthy, by taking hypoallergenic cupcakes over a long period, more than
      half of patients are hyposensitized and become able to eat normal wheat products.
      This suggests that the hypoallergenic wheat flour can act as anti-allergenic via
      allergen-specific immunotolerance. This series of studies was followed by
      expansive research on food allergy: analysis of epitopes of bovine serum albumin
      (the major beef allergen), isolation and identification of inhibitory peptides
      for allergen absorption at the intestine, evaluation of hesperetin as an
      inhibitor of degranulation of mast cells, and the development of PCR detection
      methods for verifying allergen labeling and for identifying hidden allergic
      ingredients in processed foods.

PMID- 18323653
TI  - Isolation of carrot Argonaute1 from subtractive somatic embryogenesis cDNA
      library.
AB  - Carrot Argonaute1 (C-Ago1) was isolated from a subtractive cDNA library to obtain
      somatic embryogenesis related genes. C-Ago1 has three conserved domains, which
      are found in all other Argonautes. C-Ago1 has specific expression during somatic
      embryogenesis, which indicates that microRNA gene expression controlling system
      is required for somatic embryogenesis.

PMID- 18323654
TI  - Stabilization of p53 is involved in quercetin-induced cell cycle arrest and
      apoptosis in HepG2 cells.
AB  - There is evidence for defects in the mechanisms that allow the activation of p53
      in many of the cancers that retain wild-type p53. Reactivation of p53 has been
      suggested to be an effective strategy for cancer therapy in wild-type p53
      retained tumor cells. In the present study, we attempted to reactivate p53 in
      HepG2 retaining wild-type p53 by quercetin, an ubiquitous bioactive plant
      flavonoid. Our results show that quercetin inhibited the proliferation of HepG2
      cells through the induction of cell cycle arrest and apoptosis, as characterized
      by the cell cycle distribution and DNA fragmentation. Molecular data revealed
      that quercetin induced p53 phosphorylation and total p53 protein, but that it did
      not up-regulate p53 mRNA at the transcription level. Consequently, quercetin
      stimulated p21 expression and suppressed cyclin D1 expression in favor of cell
      cycle arrest. Quercetin also increased the ratio of Bax/Bcl-2 in favor of
      apoptosis with such treatment. Interestingly, quercetin inhibited p53
      ubiquitination and extended the half-life (t(1/2)) of p53 from 74 to 184 min.
      Quercetin also inhibited p53 mRNA degradation at the post-transcription stage.
      Silencing p53 with p53 small interfering RNA (siRNA) significantly abrogated the
      p53-dependent gene expression and apoptotic induction. Taken together, our data
      demonstrate that quercetin stabilized p53 at both the mRNA and protein levels to
      reactivate p53-dependent cell cycle arrest and apoptosis in HepG2 cells.

PMID- 18323655
TI  - Effects of Rosa rugosa petals on intestinal bacteria.
AB  - The effects of pulverized petal of Rosa rugosa on the growth of 10 species of
      intestinal and pathogenic bacteria were investigated. Growth of bifidobacteria
      and lactobacilli was not affected by the addition of the petal in plate
      cultivation. However, the growth of Bacteroides vulgatus, Escherichia coli,
      Staphylococcus aureus, and Bacillus cereus was completely inhibited by the
      addition of 0.1, 0.5, 0.1, and 0.05% (w/v) of the petal respectively. In liquid
      cultivation, the addition of the petal (0.5%) stimulated the growth of
      Bifidobacterium breve and slightly inhibited the growth of Lactobacillus
      salivarius. But the growth of E. coli, S. aureus, B. cereus, and Salmonella sp.
      was inhibited by nearly 50%. Hydrolyzable tannins isolated from R. rugosa,
      rugosin D, and tellimagradin II showed antibacterial activities against E. coli,
      S. aureus, B. cereus, and Salmonella sp., but little or no effect against Bif.
      breve and L. salivarius. R. rugosa petal showed selective antibacterial
      activities against intestinal and pathogenic bacteria, and the selectivity
      resembled that of prebiotics such as oligosaccharides and dietary fiber.
      Hydrolyzable tannins in R. rugosa, such as rugosin D and tellimagradin II, must
      be active constituents.

PMID- 18323656
TI  - Changes in the gene expression of C-myc and CD38 in HL-60 cells during
      differentiation induced by nicotinic acid-related compounds.
AB  - Changes in gene expression levels of c-myc and CD38 were examined during the
      differentiation of HL-60 cells to granulocytes due to three nicotinic acid
      related compounds. CD38 expression was increased by isonicotinic acid and all
      trans-retinoic acid (ATRA). Nicotinamide and nicotinamide N-oxide drastically
      decreased c-myc expression, but isonicotinic acid had no effect, suggesting that
      these compounds differentiate HL-60 to granulocytes through different pathways.
      These results should provide useful information as to the mechanisms of cell
      differentiation.

PMID- 18323657
TI  - Detection of bphAa gene expression of Rhodococcus sp. strain RHA1 in soil using a
      new method of RNA preparation from soil.
AB  - To understand the response of soil bacteria to the surrounding environment, it is
      necessary to examine the gene expression profiles of the bacteria in the soil.
      For this purpose, we developed a new method of extracting RNA from soil
      reproducibly. Using this new method, we extracted RNA from a field soil, which
      was sterilized and inoculated with Rhodococcus sp. strain RHA1, a biphenyl
      degrader isolated from gamma-hexachlorocyclohexane-contaminated soil. Data from
      agarose gel electrophoresis indicated that the extracted RNA was purified
      properly. This new method can be applied easily in the preparation of large
      amounts of RNA. Real-time reverse transcription-polymerase chain reaction (RT
      PCR) experiments performed by the TaqMan method suggested that the bphAa gene in
      this strain, which is involved in the degradation of biphenyl, was induced in the
      biphenyl amended soil.

PMID- 18323658
TI  - Expression and characterization of the Streptomyces coelicolor serine/threonine
      protein kinase PkaD.
AB  - We identified and characterized the gene encoding a new eukaryotic-type protein
      kinase from Streptomyces coelicolor A3(2) M145. PkaD, consisting of 598 amino
      acid residues, contained the catalytic domain of eukaryotic protein kinases in
      the N-terminal region. A hydrophobicity plot indicated the presence of a putative
      transmembrane spanning sequence downstream of the catalytic domain, suggesting
      that PkaD is a transmembrane protein kinase. The recombinant PkaD was found to be
      phosphorylated at the threonine and tyrosine residues. In S. coelicolor A3(2),
      pkaD was transcribed as a monocistronic mRNA, and it was expressed constitutively
      throughout the life cycle. Disruption of chromosomal pkaD resulted in a
      significant loss of actinorhodin production. This result implies the involvement
      of pkaD in the regulation of secondary metabolism.

PMID- 18323659
TI  - Complete structure, genomic organization, and expression of channel catfish
      (Ictalurus punctatus, Rafinesque 1818) matrix metalloproteinase-9 gene.
AB  - In this study, the channel catfish (CC) matrix metalloproteinase-9 (MMP-9) gene
      was cloned, sequenced, and characterized at both the cDNA and the genomic DNA
      levels. The complete sequence of the CC MMP-9 cDNA consisted of 2,551
      nucleotides, including one open reading frame and 5'- and 3'-end untranslated
      regions. The open reading frame potentially encoded a 686-amino-acid peptide with
      a calculated molecular mass (without glycosylation) of approximately 77.4 kDa,
      which included a signal peptide and potentially heavy O-glycosylation sites. CC
      MMP-9 did not have the tripeptide Arg-Gly-Asp motif. The degree of conservation
      of the CC MMP-9 amino acid sequence to human and mouse counterparts was 55%,
      while to those of other fish species was 67-74%. The full-length CC MMP-9 genomic
      DNA comprised 5,663 nucleotides, much shorter than human or mouse counterparts.
      The exon-intron structure followed the splice acceptor/donor consensus rule, and
      the sequence contained 13 exons. The MMP-9 transcript was constitutively
      expressed in restrictive CC tissues. This result should provide fundamental
      information for further exploration of the role of MMP-9 in fish pathophysiology.

PMID- 18323660
TI  - Crystal structure and functional analysis of an archaeal chromatin protein Alba
      from the hyperthermophilic archaeon Pyrococcus horikoshii OT3.
AB  - The crystal structure of the Alba protein (PhoAlba) from a hyperthermophilic
      archaeon, Pyrococcus horikoshii OT3, was determined at a resolution of 2.8 A.
      PhoAlba structurally belongs to the alpha/beta proteins and is similar not only
      to archaeal homologues but also to RNA-binding proteins, including the C-terminal
      half of initiation factor 3 (IF3-C) from Bacillus stearothermophilus, an
      Esherichia coli protein implicated in cell division (Yhhp), and an Arabidopsis
      protein of unknown function. We found by gel shift assay that PhoAlba interacts
      with both ribonuclease P (RNase P) RNA (PhopRNA) and precursor-tRNA(Tyr) (pre
      tRNA(Tyr)) in P. horikoshii. However, the addition of PhoAlba to reconstituted
      particles composed of PhopRNA and four or five protein subunits had little
      influence on either the pre-tRNA processing activity or the optimum temperature
      for the processing activity. These results suggest that PhoAlba contributes
      little to the catalytic activity of P. horikoshii RNase P.

PMID- 18323661
TI  - Two proteins with diaphorase activity from Clostridium thermocellum and Moorella
      thermoacetica.
AB  - Two high-molecular-weight rubredoxin genes (hrb) from Clostridium thermocellum
      and Moorella thermoacetica were expressed in Escherichia coli and their
      translated products (Hrb) were characterized. M. thermoacetica Hrb showed strong
      diaphorase activity. In contrast, C. thermocellum Hrb, containing neither FMN nor
      FAD in the molecule, showed flavin reductase activity with moderate diaphorase
      activity. Both enzymes were optimally active at about 50 degrees C.

PMID- 18323662
TI  - Cloning and expression of a Clostridium kluyveri gene responsible for diaphorase
      activity.
AB  - A small enzyme showing diaphorase activity was purified from culture supernatant
      of Clostridium kluyveri and its N-terminal amino acid sequence was determined.
      This sequence identified a gene (diaA) encoding a protein (DiaA) of 229 amino
      acids with a predicted molecular weight of 24,981 in the genomic DNA sequence
      database of C. kluyveri constructed by the Research Institute of Innovative
      Technology for the Earth. The predicted protein was composed of a flavin
      reductase-like domain and a rubredoxin-like domain from its N-terminus. The diaA
      gene was cloned into an expression vector and expressed in an Escherichia coli
      recombinant. Recombinant enzyme rDiaA showed NADH/NADPH diaphorase activity with
      2,6-dichlorophenolindophenol and nitro blue tetrazolium. The enzyme was most
      active at pH 8.0 at 40 degrees C. The UV-visible absorption spectrum and thin
      layer chromatography (TLC) analyses indicated that one rDiaA molecule contained a
      tightly bound FMN molecule as a prosthetic group. An iron molecule was also
      detected in an enzyme molecule.

PMID- 18323663
TI  - Asaia lannaensis sp. nov., a new acetic acid bacterium in the
      Alphaproteobacteria.
AB  - Asaia lannaensis sp. nov. was described for two strains isolated from flowers of
      the spider lily collected in Chiang Mai, Thailand. The isolates produced acetic
      acid from ethanol on ethanol/calcium carbonate agar, differing from the type
      strains of Asaia bogorensis, Asaia siamensis, and Asaia krungthepensis, but did
      not grow in the presence of 0.35% acetic acid (v/v). The new species is the
      fourth of the genus Asaia, the family Acetobacteraceae.

PMID- 18323664
TI  - Identification and characterization of mouse type II platelet-derived growth
      factor receptor alpha transcript.
AB  - Recently, we identified a novel human platelet-derived growth factor (PDGF)
      receptor alpha mRNA (type II) that differs from the known human PDGF receptor
      alpha mRNA (type I) only in its 5'-untranslated region and is regulated by E2F-1.
      In this study, we determined the nucleotide sequence of the mouse type II PDGF
      receptor alpha mRNA and found that the expression of this transcript was
      regulated by E2F-1 through an E2F-1-responsive sequence located +711/+718
      downstream of the transcription start site of the type I transcript. Furthermore,
      we observed embryo-predominant expression of the type II transcript.

PMID- 18323665
TI  - Expression and characterization of endochitinase C from Serratia marcescens
      BJL200 and its purification by a one-step general chitinase purification method.
AB  - In this study we cloned, expressed, purified, and charaterized chitinase C1 from
      Serratia marcescens strain BJL200. As expected, the BJL200-ChiC1 amino acid
      sequence of this strain was highly similar to sequences of ChiC1 identified in
      two other strains of S. marcescens. BJL200-ChiC1 was overproduced in E. coli by
      the T7 expression system, and purified by a one-step hydrophobic interaction
      chromatography (HIC) with phenyl-sepharose. BJL200-ChiA and BJL200-ChiB had an
      approximately 30-fold higher k(cat) and 15 fold-lower K(m) than BJL200-ChiC1 for
      the oligomeric substrate 4-methylumbelliferyl-beta-D-N-N'-N''
      triacetylchitotrioside, while BJL200-ChiC1 was 10-15 times faster than BJL200
      ChiB and BJL200-ChiA in degrading the polymeric substrate CM-chitin-RBV. BJL200
      ChiC1 degradation of beta-chitin resulted in a range of different chito
      oligosaccharides (GlcNAc)(2) (main product), GlcNAc, (GlcNAc)(3), (GlcNAc)(4),
      and (GlcNAc)(5), indicating endo activity. The purification method used for
      BJL200-ChiC1 in this study is generally applicable to family 18 chitinases and
      their mutants, including inactive mutants, some of which tend to bind almost
      irreversibly to chitin columns. The high specificity of the interaction with the
      (non-chitinous) column material is mediated by aromatic residues that occur in
      the substrate-binding clefts and surfaces of the enzymes.

PMID- 18323666
TI  - The role of Arg114 at subsites E and F in reactions catalyzed by hen egg-white
      lysozyme.
AB  - To understand better the role of subsites E and F in lysozyme-catalyzed
      reactions, mutant enzymes, in which Arg114, located on the right side of subsites
      E and F in hen egg-white lysozyme (HEL), was replaced with Lys, His, or Ala, were
      prepared. Replacement of Arg114 with His or Ala decreased hydrolytic activity
      toward an artificial substrate, glycol chitin, while replacement with Lys had
      little effect. Kinetic analysis with the substrate N-acetylglucosamine pentamer,
      (GlcNAc)(5), revealed that the replacement for the Arg residue reduced the
      binding free energies of E-F sites and the rate constant of transglycosylation.
      The rate constant of transglycosylation for R114A was about half of that for the
      wild-type enzyme. (1)H-NMR analysis of R114H and R114A indicated that the
      structural changes induced by the mutations were not restricted to the region
      surrounding Arg114, but rather extended to the aromatic side chains of Phe34 and
      Trp123, of which the signals are connected with each other through nuclear
      Overhauser effect (NOE) in the wild-type. We speculate that such a conformational
      change causes differences in substrate and acceptor binding at subsites E and F,
      lowering the efficiency of glycosyl transfer reaction of lysozyme.

PMID- 18323667
TI  - Tanticharoenia sakaeratensis gen. nov., sp. nov., a new osmotolerant acetic acid
      bacterium in the alpha-Proteobacteria.
AB  - Tanticharoenia sakaeratensis gen. nov., sp. nov. is proposed for three strains
      isolated from soil collected in Thailand. The three strains, AC37(T), AC38, and
      AC39, were included within a lineage comprising the genera Asaia, Kozakia,
      Swaminathania, Neoasaia, Acetobacter, Gluconobacter, and Saccharibacter in a
      phylogenetic tree based on 16S rRNA gene sequences, but formed a quite different,
      independent cluster. Pair-wise sequence similarities of strain AC37(T) were 96.5
      92.1% to the type strains of Acetobacter aceti, Gluconobacter oxydans, Acidomonas
      methanolica, Gluconacetobacter liquefaciens, Asaia bogorensis, Kozakia baliensis,
      Swaminathania salitolerans, Saccharibacter floricola, Neoasaia chiangmaiensis,
      and Granulibacter bethesdensis. The three strains had DNA base compositions
      comprising respectively 65.6, 64.5, and 65.6 mol % G+C with a range of 1.1 mol %,
      and formed a single species. Phenotypically, the three strains did not oxidize
      acetate or lactate, but grew on 30% D-glucose (w/v). Chemotaxonomically, they had
      Q-10. The type strain is AC37(T) (= BCC 15772(T) = NBRC 103193(T)).

PMID- 18323668
TI  - Serum cholesterol-decreasing effect of heat-moisture-treated high-amylose
      cornstarch in cholesterol-loaded rats.
AB  - Rats were fed on a diet containing cholesterol (Chol) at a level corresponding to
      the standard Chol intake in humans, and the influence of heat-moisture-treated
      high-amylose cornstarch (HHA) on their serum Chol level was investigated. HHA
      decreased the serum level of Chol in rats fed on the diet containing 0.1% Chol,
      which corresponds to a Chol intake in humans of 800 mg/d, although the liver
      levels of Chol increased in these rats. HHA did not influence the fecal excretion
      of Chol/bile acids. It is possible that the decrease in serum Chol level in the
      rats fed on the high-Chol diet can be attributed to the promotion of Chol uptake
      in the liver.

PMID- 18323669
TI  - Long-term ingestion of insoluble dietary fiber increases luminal mucin content,
      but has no effect on nutrient absorption in rats.
AB  - We reexamined the hypothesis that increased mucin secretion by the ingestion of
      insoluble dietary fiber (IDF) could affect small intestinal nutrient absorption.
      Polystyrene foam (PSF) was used as IDF. Rats were fed a diet with or without 90 g
      of PSF/kg for 1, 2 and 4 wk. At the end of each period, a glucose and ovalbumin
      (OVA) solution was intubated after 12 h of food depletion, and the changes in
      serum concentrations of these components were monitored. Luminal mucin was
      measured as O-linked oligosaccharide chains and also determined by ELISA. In all
      periods, the luminal mucin content was greater in the PSF-fed group than in the
      fiber-free control. However, the changes in serum glucose and OVA concentrations
      were comparable between the groups at any time during any period. These results
      show that the enhancement of luminal mucin secretion lasted even after chronic
      ingestion of IDF, but that the increased luminal mucin content had no effect on
      the rate of luminal nutrient absorption.

PMID- 18323670
TI  - Characterizing the lipid-lowering effects and antioxidant mechanisms of tomato
      paste.
AB  - Lycopene is known to decrease cardiovascular risks. The objective of this study
      was to investigate the molecular mechanisms of tomato paste containing
      approximately 0.1% lycopene in regulating lipid metabolism and oxidation.
      Hamsters fed 3% or 9% tomato paste containing 0.2% cholesterol were subjected to
      total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein
      (HDL), and triglyceride (TG) measurements. Our results showed reduced rates of
      serum TC and LDL levels due to 9% tomato paste were 14.3% and 11.3% respectively.
      Concentrations of 3% and 9% of tomato paste after 8 weeks of feeding
      significantly increased serum HDL levels, by 19.4% and 28.8% respectively. After
      ingestion of tomato paste for 8 weeks, the plasma malondialdehyde (MDA) levels
      significantly decreased, by 80.18% and 89.33% respectively, as compared to the
      cholesterol group. MDA and diene conjugation assays indicated the potent
      antioxidant activity of the tomato paste. The increased activities of superoxide
      dismutases (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), further
      supported the antioxidant effects of the tomato paste. Two dimension-gel
      electrophoresis (2-DE) analysis revealed that carbonic anhydrase III (CAIII) and
      adenylate kinase 2 (AK2) may be two important regulators involved in the anti
      lipid and antioxidant effects of tomato paste, opening new insight into the
      nutritional value of tomato in public health promotion.

PMID- 18323671
TI  - Identification of genes differentially expressed in mouse fetuses from
      streptozotocin-induced diabetic pregnancy by cDNA subtraction.
AB  - Epidemiological studies have shown that the risks of fetal malformation such as
      neural tube defects increase in diabetic pregnancy. To explore the mechanism of
      fetal malformation induced by diabetes, cDNA subtraction using mouse embryos
      (E9.5) of diabetic dams and those of controls was performed to identify
      differentially expressed genes. The expression level of genes identified by cDNA
      subtraction was further verified by quantitative RT-PCR using E8.5 embryos, and
      differential expression of 4 genes, Brcc3, Commd3, Ddx1, and SET was confirmed.
      We also analyzed the expression level of neural tube defect-related genes, and
      found that Folbp1, EphrinA5 and Sox10 were differentially expressed. Altered
      expression of these genes mostly persisted throughout the later stages of the
      development (E10.5-14.5). Hierarchical clustering analysis showed correlation
      between expression levels of these genes, suggesting that these genes
      cooperatively play a role in embryonic development. Our results suggest that an
      altered gene expression profile in embryos underlies the development of
      congenital malformation in diabetic pregnancies.

PMID- 18323672
TI  - Significant association of serum albumin with severity of retinopathy and
      neuropathy, in addition to that of nephropathy, in Japanese type 2 diabetic
      patients.
AB  - OBJECTIVE: The aim of this study was to determine the association between serum
      albumin and the severity of microvascular complications and presence of coronary
      artery disease in type 2 diabetic patients. PATIENTS AND METHODS: The presence of
      diabetic complications was assessed in a total of 130 Japanese patients with type
      2 diabetes mellitus. Retinopathy was classified as absent, simple or
      proliferative diabetic retinopathy. Neuropathy was considered to be present when
      the patient showed absence of Achilles tendon reflex, and also evaluated by
      measuring the median motor nerve conduction velocity (MNCV) in the nerve
      conduction study. RESULTS: In relation to retinopathy, there were 83 patients
      with no retinopathy (absent), 26 with simple retinopathy and 21 with
      proliferative retinopathy. There was a significant difference in the serum
      albumin level between the "absent" group and the other two groups. In relation to
      nephropathy, there were 68 patients with no evidence of nephropathy, 49 with
      microalbuminuria and 13 with proteinuria. The results of logistic regression
      analysis with adjustment for three variables (age, gender, serum CRP) revealed
      that serum albumin was independently related to proliferative retinopathy and
      proteinuria. In relation to neuropathy, serum albumin was found to be
      significantly related to the absence of Achilles tendon reflex, MNCV, and MFWL.
      The results of multiple regression analysis with adjustment for three variables
      (age, gender, serum CRP) revealed that serum albumin was independently related to
      MNCV and MFWL. CONCLUSIONS: Serum albumin was significantly associated with the
      severity of retinopathy and neuropathy.

PMID- 18323673
TI  - A male case of nonclassical 21-hydroxylase deficiency first manifested in his
      sixties with adrenocortical incidentaloma.
AB  - Nonclassical form of 21-hydroxylase deficiency (NC 21OHD) as a frequent variant
      on the milder end of the disease spectrum has been widely acknowledged, but its
      potential contribution to adrenocortical tumorigenesis has not been fully
      elucidated. We report a 66-year old male case of bilateral adrenocortical
      incidentaloma, associated with partial 21OHD without any episodes of
      hypoadrenocorticism in his past history. He was demonstrated to be a compound
      heterozygous mutant of CYP21A2 gene (IVS2-13A/C>G/I172N). The two tumors in the
      left adrenal, which were interpreted as myelolipoma by imaging studies, were
      followed by sequential observation, whereas the contralateral large solid tumor
      associated with inhomogeneous radiological appearance was subsequently removed.
      The resected tumor was diagnosed an adrenocortical adenoma, which was devoid of
      P450c21 immunoreactivity. 21OHD is often associated with benign adrenocortical
      tumors, but bilateral adrenal tumors with heterogeneous components in both
      adrenals have not been reported to the best of our knowledge.

PMID- 18323674
TI  - Lipopolysaccharide stimulates proopiomelanocortin gene expression in AtT20
      corticotroph cells.
AB  - While lipopolysaccharides (LPS) are known to activate the hypothalamo-pituitary
      adrenal axis, their direct effects on proopiomelanocortin (POMC) and
      adrenocorticotropin (ACTH) expression at the pituitary level through Toll-like
      receptors (TLRs) remain unclear. In this study, we examined the effects of LPS on
      ACTH secretion and the transcription of the POMC gene in the AtT20 mouse
      pituitary corticotroph cell line. RT-PCR analysis showed that TLR1-4 and 6
      subtype mRNAs were expressed in AtT20 cells. When the cells were treated with
      LPS, a significant increase in the 5'-promoter activity of POMC gene was observed
      at 24 h, without any stimulatory effect on ACTH secretion. LPS also stimulated
      the expression of c-Fos gene and protein, and AP1-, but not NF-kappaB-, mediated
      transcription. Overall, our data show the expression of TLRs in the pituitary
      corticotroph cells, and suggest the direct stimulatory effect of LPS on POMC gene
      expression via TLR (probably TLR4), although the intracellular signaling pathways
      in the corticotroph may be different from those in immune cells.

PMID- 18323675
TI  - Correlation between clinical phenotypes and X-inactivation patterns in six female
      carriers with heterozygote vasopressin type 2 receptor gene mutations.
AB  - About 90% of patients with congenital nephrogenic diabetes insipidus (NDI) have
      vasopressin type 2 receptor (V2R) gene mutations that are inherited in an X
      linked recessive manner. Although most female carriers are asymptomatic, some
      female carriers show polydipsia and polyuria. The reason why female carriers show
      NDI symptoms is explained by skewed X-inactivation. We studied X-inactivation
      patterns of six female carriers with heterozygote V2R gene mutations. The X
      inactivation pattern in peripheral blood leukocytes was examined using
      methylation analysis of the polymorphic CAG repeat in the androgen receptor gene.
      Two asymptomatic female carriers showed random X-inactivation (61.9% and 60.7%).
      Skewed X-inactivation patterns (71.6%, 79.4%, and 91.2%) occurring preferentially
      to normal X alleles were recognized in three female carriers who showed clinical
      NDI symptoms. However, in one female carrier who showed clinical NDI symptoms,
      random X-inactivation (55.4%) was recognized. In conclusion, the clinical NDI
      phenotypes may correlate with the X-inactivation patterns in female carriers with
      heterozygote V2R gene mutations. However, in some female carriers, we cannot
      predict the clinical phenotypes by the evaluation of the X-inactivation patterns
      in peripheral blood leukocytes, because X-inactivation ratios within an
      individual are sometimes different between tissues.

PMID- 18323676
TI  - Ghrelin in pathological conditions.
AB  - The recently identified gastric hormone ghrelin was initially described as a
      natural Growth Hormone Secretagogue Receptor ligand. Apart from ghrelin's first
      discovered action, which was the stimulation of Growth Hormone release,
      implications for many other functions have been reported. It seems that ghrelin
      exhibits an important role in conditions related to processes regulating
      nutrition, body composition and growth, as well as heart, liver, thyroid or
      kidney dysfunction. In this review, current available knowledge about ghrelin's
      role in various pathological conditions is presented.

PMID- 18323677
TI  - Competition during submerged mixed culture of Geotrichum candidum and Penicillium
      camembertii on glucose and threonine.
AB  - Geotrichum candidum and Penicillium camembertii were cultivated in pure and mixed
      cultures on glucose and threonine. In pure cultures, G. candidum used glucose as
      a carbon and an energy source and threonine only as a nitrogen source, even after
      glucose exhaustion. Contrarily, when growing in isolation, P. camembertii used
      simultaneously threonine and glucose as carbon sources. A diauxic growth was
      recorded during the mixed culture of both species, which competed for glucose,
      the sole carbon source available for G. candidum growth, leading to higher
      glucose consumption rates than those recorded during pure cultures, while after
      glucose exhaustion, low growth was recorded in a second step, showing a
      'competition' for threonine, the sole remaining carbon and nitrogen sources,
      confirmed by the increase of 1.0+/-0.1 log of the G. candidum Colony Forming
      Units. 'Competition' between G. candidum and P. camembertii for the limiting
      substrate was found to have a positive effect on growth, since it did not lead to
      the annihilation of one species, as usually observed, but in their coexistence,
      leading to a rather similar final number of the CFUs for the two populations.
      'Competition' resulted in the absence of assimilation of the second available
      carbon substrate (lactate) as previously observed, or its use only as a nitrogen
      source, as was the case for threonine in this work.

PMID- 18323678
TI  - Survival of freeze-dried bacteria.
AB  - The aim of this study was to investigate the survival of freeze-dried bacterial
      species stored at the International Patent Organism Depository (IPOD) and to
      elucidate the characteristics affecting survival. Bacterial strains were freeze
      dried, sealed in ampoules under a vacuum (<1 Pa), and stored in the dark at 5
      degrees C. The survival of a variety of species following storage for up to 20
      years was analyzed. The survival of freeze-dried species was analyzed in terms of
      two stages, freeze-drying and storing. Nonmotile genera showed relatively high
      survival after freeze-drying. Motile genera with peritrichous flagella showed low
      survival rates after freeze-drying. Vibrio and Aeromonas, which produce numerous
      flagella, showed very low survival rates. In Lactobacillus, non-trehalose
      fermenting species showed better survival rates after freeze-drying than did
      fermenting species, and those species with teichoic acid in the cell wall showed
      lower survival rates during storage than species with teichoic acid in the cell
      membrane. Human pathogenic species of Corynebacterium, Bacillus, Streptococcus,
      and Klebsiella showed lower survival rates during storage than nonpathogenic
      species within the same genus. Among Pseudomonas species, P. chlororaphis, the
      only species tested that forms levan from sucrose, showed the lowest survival
      rate during storage in the genus. Survival rates of Gram-negative species during
      storage tended to be lower than those of Gram-positive species, though
      Chryseobacterium meningosepticum had stable survival during storage. The
      conclusion is that smooth cell surfaces (i.e., no flagella) and lack of trehalose
      outside the cytoplasm improved survival rates after freeze-drying. Because
      desiccation is important for survival during storage, the presence of
      extracellular polysaccharides or teichoic acids is disadvantageous for long-term
      survival. The lower survival rates of freeze-dried Gram-negative bacteria
      compared with those of Gram-positive bacteria may be attributed to the thinner
      peptidoglycan layer and the presence of lipopolysaccharides on the cell wall in
      the former species.

PMID- 18323679
TI  - Fecal microbiota of a dugong (Dugong dugong) in captivity at Toba Aquarium.
AB  - A captive female dugong at Toba Aquarium (Japan) was examined to describe the
      microbiota of its lower digestive tracts using the molecular-biological
      technique, a culture-independent method. The phylogenetic analysis of bacterial
      16S rRNA genes was conducted for fecal samples, which were taken at 3 different
      periods. Based on phylogenetic analysis of these sequences, the representatives
      of six bacterial phyla could be identified: Actinobacteria (0.7%), Bacteroidetes
      (15%), Firmicutes (83.1%), Lentisphaerae (0.1%), Proteobacteria (0.1%), and
      Verrucomicrobia (1.0%), suggesting the existence of bacterial species newly found
      not only in the digestive tract but also in natural field.

PMID- 18323680
TI  - Comparison of pulsed-field gel electrophoresis patterns of antimicrobial
      resistant Escherichia coli and enterococci isolates from the feces of livestock
      and livestock farmers in Japan.
AB  - Seven hundred thirty-nine animal strains and 662 livestock-farmer strains,
      consisting of Escherichia coli and enterococci, were examined for their pulsed
      field gel electrophoresis (PFGE) and antimicrobial-resistance patterns. Two
      hundred fifty-eight and 203 PFGE patterns were found among 739 animal strains
      isolated from animals comprising broilers, pigs and cattle, and 662 human strains
      isolated from livestock farmers, respectively, from 27 farms in Japan. These
      results demonstrated that the PFGE patterns found among E. coli and enterococci
      strains from animals and livestock-farmers were heterogeneous and considerably
      diverse. The strains having both the identical PFGE pattern and the same drug
      resistance pattern were defined as a single clone in this study. Seven types of
      E. coli and enterococci clones were shared among animals within the same farms
      and between the different farms housing the same animal species. The 25 strains
      (3.4%) of 739 E. coli and enterococci animal strains belonged to these seven
      types of clones. Only three types of E. coli clones were shared among animals
      between the different farms housing different animal species, but no identical E.
      faecalis or E. faecium clones were found between different animal species farms.
      The 15 strains (2.0%) of 739 E. coli and enterococci animal strains belonged to
      these three types of clones. Additionally, the 11 strains (1.5%) of 739 E. coli
      and enterococci strains isolated from animals were identical clones to strains
      isolated from livestock farmers of the same farm. These results suggest that the
      transmission of animal clones to livestock farmers or vice versa is less common.

PMID- 18323681
TI  - Identification and characterization of Lactic Acid Bacteria isolated from Tibetan
      Qula cheese.
AB  - Fourteen strains of Lactic Acid Bacteria (LAB) isolated from Qula, a Tibetan
      traditional yak cheese, were divided into four groups (A-D) according to
      morphological and biochemical characteristics. On the basis of the 16S rRNA gene
      sequence analysis, group A and group B strains were placed in the cluster making
      up the genus Leuconostoc, which together with Leuconostoc mesenteroides and
      Leuconostoc pseudomesenteroides, formed a distinct cluster. The group C strain
      was clearly identified as Enterococcus faecium by forming a very well defined
      cluster with this species. The group D strains were placed in the lactobacilli
      cluster with Lactobacillus plantarum and Lactobacillus pentosus being the closely
      related species. On the basis of DNA-DNA hybridization, strains in the groups A,
      B, C and D were identified as Leuconostoc mesenteroides subsp. dextranicum,
      Leuconostoc pseudomesenteroides, Enterococcus faecium and Lactobacillus
      plantarum, respectively. Leuconostoc mesenteroides subsp. dextranicum was the
      dominate member of the population.

PMID- 18323682
TI  - Pseudomonas japonica sp. nov., a novel species that assimilates straight chain
      alkylphenols.
AB  - A bacterial strain, WL(T), which was isolated from an activated sludge, was able
      to degrade alkylphenols. 16S rDNA sequence analysis indicated that strain WL(T)
      belonged to the genus Pseudomonas (sensu stricto) and formed a monophyletic clade
      with the type strain of Pseudomonas graminis and other members in the Pseudomonas
      putida subcluster with sequence similarity values higher than 97%. Genomic
      relatedness based on DNA-DNA hybridization of strain WL(T) to these strains is 2
      41%. Strain WL(T) contained ubiquinone-9 as the main respiratory quinone, and the
      G+C content of DNA was 66 mol%. The organism contained hexadecanoic acid (16:0),
      hexadecenoic acid (16:1) and octadecenoic acid (18:1) as major cellular fatty
      acids. The hydroxy fatty acids detected were 3-hydroxydecanoic acid (3-OH 10:0),
      3-hydroxydodecanoic acid (3-OH 12:0) and 2-hydroxydodecanoic acid (2-OH 12:0).
      These results, as well as physiological and biochemical characteristics clearly
      indicate that the strain WL(T) represents a new Pseudomonas species, for which
      the name Pseudomonas japonica is proposed. The type strain is strain WL(T) (=IAM
      15071T=TISTR 1526T).

PMID- 18323683
TI  - Distribution of five vibrio virulence-related genes among Vibrio harveyi
      isolates.

PMID- 18323684
TI  - Purification and characterization of a biosurfactant produced by Issatchenkia
      orientalis SR4.

PMID- 18323685
TI  - Relationships between the conception rate of estrus synchronization using
      estradiol benzoate and CIDR (progesterone) and other parameters in holstein
      lactating dairy cows.
AB  - The purpose of this study was to determine the relationships between conception
      rate and other parameters before estrus synchronization with a Controlled
      Internal Drug Release Device (CIDR) and estradiol benzoate (EB). In the estrus
      synchronization program, animals were injected with 2 mg EB and then received a
      CIDR. Seven days later, the CIDR was removed and the animals were given an
      injection of Prostaglandin F(2alpha). Twenty-four hours later, they received an
      injection of 1 mg EB, and they were artificially inseminated 24 h after that.
      This program was applied to 258 Holstein cows in Tohoku-machi (Aomori, Japan).
      Blood was collected at the beginning of the program, and the conception rate was
      determined about 40 days after insemination. The relationships among conception
      rate, blood biochemical values, age, body condition score and days in milk were
      statistically analyzed to determine better conditions for cow conception. The
      conception rate of the cows in the high progesterone group (more than 1 ng/ml,
      P(4)+) was significantly higher than that of the low progesterone group (less
      than 1 ng/ml, P(4)-; 47.9% vs. 28.6% P<0.01). In the P(4)- groups, the serum
      phospholipid level was significantly higher in the conception group than in the
      non-conception group, and the same tendency was seen in the P(4)+ groups. Blood
      urea nitrogen (BUN), albumin (Alb), and total cholesterol (TChol) were
      significantly higher in the conception group compared with the non-conception
      group, but no with P(4) was observed. We concluded that 1) the conception rate of
      the P(4)- group was remarkably low, that 2) the low conception rate and low P(4)
      level was related to a low PL level and that 3) BUN, Alb and TChol were higher in
      the conception group, although no relation with P(4) was found.

PMID- 18323686
TI  - Beauty in the architecture of living organisms.

PMID- 18323687
TI  - First disclosure of lipid droplet substructure and myelin translucency in
      embedment-free section electron microscopy.
AB  - In conventional transmission electron microscopy (EM), thinly sectioned specimens
      embedded in epoxy resin are observed. However, because of a substantial level of
      electron density of epoxy resin, the possibility cannot be ruled out that bio
      structures having electron density similar to that of epoxy resin are not clearly
      recognized and thus are neglected or misinterpreted in conventional EM. This was
      the reason to require for embedment-free EM. Embedment-free sections have already
      been made available reliably by transient embedding in polyethylene glycol (PEG)
      and subsequent de-embedding through immersion in water, and further by critical
      point drying, and this embedment-free EM is thus termed PEG-EM. However, this PEG
      EM has not been successful to attract reasonable attention from electron
      microscopists and instead been misunderstood as a non-reliable method. In this
      paper, the remarkably enhanced contrast and electron translucency of any
      observation targets in PEG-EM are clearly demonstrated by comparing with images
      in conventional EM of adipocytes and neural myelin as examples. These features of
      PEG-EM, together with faithful correspondence in EM images of any individual
      substructures between the two methods, confirm the reliability of PEG-EM.
      Furthermore, the much higher thickness of embedment-free sections together with
      these features makes the PEG-EM more advantageous than the conventional EM for
      three-dimensional appreciation of structural elements, which is made by stereo
      viewing of sections or by EM tomography. Therefore, the PEG-EM is regarded as an
      important adjunct to the conventional EM for histological studies and wide
      application of this method may unravel a new level of histology.

PMID- 18323688
TI  - Molecular mechanisms governing competitive synaptic wiring in cerebellar Purkinje
      cells.
AB  - Cerebellar Purkinje cells (PCs) play a principal role in motor coordination and
      motor learning. To fulfill these functions, PCs receive and integrate two types
      of excitatory inputs, climbing fiber (CF) and parallel fiber (PF). CFs are
      projection axons from the inferior olive, and convey error signals to PCs. On the
      other hand, PFs are T-shaped axons of cerebellar granule cells, and convey
      sensory and motor information carried through the pontocerebellar and
      spinocerebellar mossy fiber pathways. The most remarkable feature of PC circuits
      is the highly territorial innervation by these two excitatory afferents. A single
      climbing CF powerfully and exclusively innervates proximal PC dendrites, whereas
      hundreds of thousands of PFs innervate distal PC dendrites. Recent studies using
      gene-manipulated mice have been elucidating that the PC circuitry is formed and
      maintained by molecular mechanisms that fuel homosynaptic competition among CFs
      and heterosynaptic competition between CFs and PFs. GluRdelta2 (a PC-specific
      glutamate receptor) and precerebellin or Cbln1 (a granule cell-derived secretory
      protein) cooperatively work for selective strengthening of PF-PC synapses, and
      prevent excessive distal extension of CFs that eventually causes multiple
      innervation at distal dendrites. In contrast, P/Q-type Ca2+ channels, which
      mediate Ca2+ influx upon CF activity, selectively strengthen the innervation by a
      single main CF, and expel PFs and other CFs from proximal dendrites that it
      innervates. Therefore, we now understand that owing to these mechanisms,
      territorial innervation by CFs and PFs is properly structured and mono
      innervation by CFs is established. Several key issues for future study are also
      discussed.

PMID- 18323689
TI  - The EFA6 family: guanine nucleotide exchange factors for ADP ribosylation factor
      6 at neuronal synapses.
AB  - ADP ribosylation factor 6 (ARF6) is a member of the ARF family of small GTPases,
      which mediates a variety of neuronal functions accompanying the structural
      changes of developing and mature neurons through its regulation of actin
      cytoskeleton reorganization and membrane traffic. The activation of ARF6 is
      strictly regulated by guanine nucleotide exchange factors (GEFs). The EFA6 family
      is the first member that was identified to be a specific GEF for ARF6 and
      comprises four structurally related polypeptides (EFA6A, EFA6B, EFA6C and EFA6D).
      Since the cellular and subcelllular localization of GEFs is a critical
      determinant for the spatiotemporal activation of ARF6 in neurons, I have focused
      on the EFA6 family from the anatomical point of view to understand the neuronal
      functions of ARF6. Three members of the EFA6 family (EFA6A, EFA6C and EFA6D) are
      abundantly expressed in the mouse brain with distinct spatiotemporal patterns.
      Interestingly, they are enriched particularly in the postsynaptic density
      fraction, shedding light on the importance of the EFA-ARF6 pathway in neuronal
      synapses. Here, I will review the recent advances in the expression and functions
      of the EFA6 family in the nervous system.

PMID- 18323690
TI  - Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in
      cells, organs, and animals: history and perspective.
AB  - Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid
      containing two acyl chains, to convert phosphatidic acid. DG is produced through
      phosphoinositide turnover within the membrane and is well known to act as a
      second messenger that modulates the activity of protein kinase C in the cellular
      signal transduction. Recent studies have revealed that DG also activates several
      proteins, including Ras guanine-nucleotide releasing protein and ion channels
      such as transient receptor potential proteins. Therefore, DGK is thought to
      participate in a number of signaling cascades by modulating levels of DG.
      Previous studies have disclosed that DGK is composed of a family of the isozymes,
      which differ in the structure, enzymological property, gene expression and
      localization, subcellular localization, and binding molecules. The present review
      focuses on the stories of phosphoinositide turnover and DG, including historical
      views, structural features, metabolism, and relevant cellular phenomena, together
      with the characteristics of DGK isozymes and the pathophysiological findings on
      animal studies using knockout mice and models for human diseases. Now it is being
      revealed that the structural and functional diversity and heterogeneity of and
      around DGK support the proper arrangement of the complex signal transduction
      machinery.

PMID- 18323691
TI  - Fatty acid binding protein: localization and functional significance in the
      brain.
AB  - Long chain fatty acids are important nutrients for brain development and
      function. However, the molecular basis of their actions in the brain is still to
      be clarified. Fatty acid-binding proteins (FABPs) belong to the multigene family
      of the intracellular lipid-binding protein. FABPs bind to long chain fatty acids,
      being involved in the promotion of cellular uptake and transport of fatty acids,
      the targeting of fatty acids to specific metabolic pathways, and the regulation
      of gene expression. FABPs are widely expressed in mammalian tissues, with
      distinct expression patterns for the individual protein. Although FABPs have been
      implicated to serve as regulators in systemic cellular metabolic pathways, recent
      studies have demonstrated the ability of FABPs to regulate functions of the
      brain, one of the most fat-enriched tissues in the body. This review summarizes
      the localization of FABPs in the brain, and recent progress in elucidating the
      function of FABPs in the brain.

PMID- 18323692
TI  - Expression of heat shock protein 27 with the transition from proliferation to
      differentiation of acinar precursor cell in regenerating submandibular gland of
      rats.
AB  - Heat shock protein 27 (Hsp27) has been suggested to participate in the cell
      proliferation and differentiation during tissue development. In fact, we have
      demonstrated the transient occurrence of Hsp27 during the differentiation of
      salivary gland acinar cells in postnatal rats. The purpose of the present study
      is to explore the potential role of Hsp27 in the proliferation and
      differentiation of the acinar cells during regeneration of the salivary gland.
      Using the experimental regeneration model of the rat submandibular gland after
      the release of duct ligation, the spatio-temporal localization of Hsp27 was
      investigated in immunohistochemistry in regenerating acini. No epithelial cells
      were immunoreactive for Hsp27 immediately after unligation, but Hsp27
      immunoreactive cells were observed in regenerating acini located at the end
      portion of survived ductal tissues on the third day after unligation. The number
      of Hsp27-immunoreactive cells in regenerating acini reached its peak on the 5th
      day after unligation, and started to decline on the 7th day. They were
      undetectable on the 14th day. Importantly, the increase in the number of Hsp27
      immunoreactive cells was preceded by the decline in the cell proliferative
      activity, and Hsp27-immunoreactivity declined and disappeared in conjunction with
      the progression of acinar cell differentiation, as judged by the double
      immunostaining for Hsp27 and proliferating cell nuclear antigen, a cell
      proliferation marker, or glycine-rich protein-alpha, a specific marker of
      differentiated acinar cells. All the findings suggest that Hsp27 is expressed
      with the transition from the cell proliferation to differentiation of the acinar
      precursor cells during the regenerating process.

PMID- 18323693
TI  - Coexpression of menin and JunD during the duct cell differentiation in mouse
      submandibular gland.
AB  - In the submandibular gland (SMG) of mice, a duct portion called the granular
      convoluted tubule (GCT) is developed preferentially in males with puberty. This
      sexual dimorphism is androgen-dependent, but the underlying molecular mechanisms
      are unclear. We have demonstrated that the expression of a transcription factor
      JunD is regulated in association with the androgen-induced differentiation of GCT
      cells from striated duct (SD) cells. Menin, a nuclear protein encoded by the MEN1
      tumor-suppressor gene, is known to bind JunD, thereby inhibiting its activity. In
      the present study, we examined the expression of menin in the mouse SMG by use of
      Northern blotting, Western blotting, and immunohistochemistry. Immunoreactivity
      for menin was higher in the female than male gland, and localized to the nuclei
      of intercalated duct cells and a subpopulation of SD cells. In contrast, GCT
      cells in males appeared negative for menin. The levels of menin in the SMG were
      increased with castration in males and decreased by repeated administration of
      testosterone to females or to castrated males. After a single administration of
      testosterone to females, many SD cells newly gained nuclear menin, which was lost
      as the cells converted to GCT cells by 48 hrs. These patterns of the expression
      and localization of menin were quite similar to those of JunD. Furthermore, the
      coimmunoprecipitation analysis of the SMG homogenates indicated that menin binds
      JunD in vivo. The present study suggests that the JunD-menin complex plays
      significant roles in the androgen-dependent differentiation of the duct system in
      the mouse SMG.

PMID- 18323694
TI  - Localization of the sulphonylurea receptor subunits, SUR2A and SUR2B, in rat
      renal tubular epithelium.
AB  - ATP-sensitive K+ (K(ATP)) channels in the kidney are considered to play roles in
      regulating membrane potential according to changes in the intracellular ATP
      concentration. They are composed of two types of subunits; the pore subunits
      (Kir6.1, Kir6.2), which are members of the inwardly rectifying K+ channel family,
      and the regulatory subunits, the sulphonylurea receptors, which belong to the ATP
      binding cassette (ABC) superfamily. The sulphonylurea receptors (SURs) are
      receptors of sulphonylureas widely used for the treatment of type 2 diabetes
      mellitus. The SURs are divided into two isoforms, SUR1 and SUR2, the latter was
      further divided into SUR2A and SUR2B. In the present study, we have investigated
      the mRNA expression by RT-PCR assay, and protein expression profiles by
      immunoblotting, immunohistochemistry, and immunoelectron microscopy with anti
      SUR2A and anti SUR2B antibodies. RT-PCR detected the presence of mRNA transcripts
      of the SUR2A and SUR2B, while SUR1 mRNA was barely detected. In immunoblotting,
      SUR2A protein was detected distinctly in the microsomal fraction, weakly in the
      mitochondrial fraction and at negligible level in the cell membrane fraction. In
      contrast, the SUR2B protein was detected intensely in the microsomal fraction,
      with a low level in the mitochondrial fraction and scarcely in the cell membrane
      fraction. In immunohistochemistry SUR2A and SUR2B proteins were widely
      distributed in renal tubular epithelial cells, glomerular mesangial cells, and
      the endothelium and the smooth muscle of blood vessels. In immunoelectron
      microscopy, the immunoreactivity was localized in the endoplasmic reticulum and
      mitochondria throughout the epithelial cells for SUR2A, and dominantly in the
      apical cytoplasm of the cells for SUR2B. In conclusion, the regulatory subunits
      of the K(ATP) channel in the rat kidney are SUR2A and SUR2B; they also are
      candidate regulatory subunits for the mitochondrial K(ATP) channel.

PMID- 18323695
TI  - The manual function test: norms for 20- to 90-year-olds and effects of age,
      gender, and hand dominance on dexterity.
AB  - Stroke is the leading cause of long-term disability. Accurate assessment of motor
      function is important for documenting disability and the effectiveness of
      rehabilitative treatment. The Manual Function Test (MFT) was developed to
      evaluate unilateral manual performance in hemiparetic patients after stroke. This
      test consists of eight items, including the pegboard task, an item assessing
      dexterity. The total MFT score can range from 0 (severely impaired) to 32 (full
      function). We sought to determine normative data and explore influences of age,
      gender, and hand dominance. Three-hundred thirty-three healthy adult subjects
      between 20 and 90 years old were studied. Total MFT scores showed negative
      relationship to age. Compared with subjects in their 20s, those 50 or more years
      old had lower total MFT scores for dominant hands, as did those 40 or more years
      old for nondominant hands. For subjects in their 30s and 50s, total MFT scores
      for women were greater than for men concerning nondominant hands. No such gender
      difference in total MFT scores was noted for dominant hands. In the pegboard
      test, the number of pegs achieved for dominant hands was related to age when age
      was 50 or over, and when age 40 or over for nondominant hands. However, rates of
      decline in numbers of pegs achieved were similar between hands. In determining
      MFT norms, total score and items testing dexterity were influenced by age,
      gender, and hand dominance.

PMID- 18323696
TI  - Normal bone growth requires optimal estrogen levels: negative effects of both
      high and low dose estrogen on the number of growth plate chondrocytes.
AB  - Endochondral bone formation at epiphyseal growth plate consists of the
      synchronized processes of chondrogenesis and cartilage ossification. Estrogen,
      the major female sex hormone, plays an important role in this process,
      particularly during the pubertal growth spurt. However, its effects on the growth
      plate are not completely understood. The aims of this study were to clarify the
      effects of estrogen on the kinetics of chondrocytes in the growth plates of 10-
      to 25-week-old female rabbits by studying the effects of ovariectomy or high-dose
      administration of estrogen on the balance between cell proliferation and death.
      Forty-eight Japanese white rabbits were divided into three groups: sham operated,
      ovariectomized, or ovariectomized with subsequent weekly injection of high dose
      estrogen from 10 weeks. The chondrocyte kinetics was investigated by
      histomorphometry and immunohistochemistry, using antibodies for caspase-3, a
      marker of apoptosis, and for proliferating cell nuclear antigen. Both
      ovariectomized and estrogen-injected rabbits showed a declination of the
      chondrocyte number although the latter animals indicated a more dramatic effect.
      Estrogen-injected rabbits showed a decrease in the cell proliferating ability
      together with an increase in chondrocytes undergoing apoptosis while ovariectomy
      mainly reduced the cell proliferating ability. Given the known importance of
      estrogen for bone growth, one would expect that ovariectomy and high-dose
      administration of estrogen would have opposite effects. However, the present
      study indicated that both low and high concentration had a similar effect: a
      decrease in the chondrocyte number compared with control, suggesting that
      estrogen has to be maintained within a narrow range for optimal bone growth.

PMID- 18323697
TI  - Hyperbaric oxygen therapy improves myocardial diastolic function in diabetic
      patients.
AB  - Myocardial diastolic dysfunction is the relaxation abnormality of ventricles that
      limits the diastolic filling and generally precedes diastolic heart failure.
      Diastolic dysfunction is a common finding in diabetes. Diabetic patients receive
      hyperbaric oxygen (HBO) therapy for non-healing lower extremity ulcers, and
      exposure to HBO therapy is known to influence cardiovascular functions. This
      study was designed to evaluate the effect of HBO therapy on myocardial diastolic
      function in diabetic patients. Thirty diabetic patients (18 male and 12 female,
      59.9 +/- 10 years old), who were planning to undergo HBO therapy, were
      consecutively enrolled. Myocardial diastolic function was evaluated by pulsed
      wave Doppler echocardiography and tissue Doppler echocardiography before the
      first HBO therapy and after the tenth HBO therapy session. HBO therapy improved
      the relaxation capability of left ventricular myocardium, which was reflected by
      reduction in E wave deceleration time of mitral valve inflow (286.1 +/- 65.8 msec
      vs 214.3 +/- 32.1 msec, p < 0.05). HBO therapy also affected favorably the
      diastolic filling dynamics of right ventricle, which was partially reflected by
      the changes in E wave peak velocity of tricuspid valve inflow (0.48 +/- 0.07
      m/sec vs 0.46 +/- 0.09 m/sec, p < 0.05). Tissue Doppler parameters of mitral
      lateral annulus, which are better correlated with ventricular relaxation, tended
      to be improved after HBO therapy, but the degree of improvement was not
      statistically significant. In conclusion, we suggest that HBO therapy may improve
      the myocardial diastolic function of diabetic patients when applied repetitively.

PMID- 18323698
TI  - Long-term visual outcome of arteriovenous adventitial sheathotomy on branch
      retinal vein occlusion induced macular edema.
AB  - PURPOSE: To evaluate long-term visual outcome of arteriovenous adventitial
      sheathotomy in BRVO-induced macular edema. METHODS: The visual outcomes of 8
      patients following vitrectomy with arteriovenous adventitial sheathotomy for BVO
      induced macular edema (surgery group) were retrospectively evaluated. The three
      year post-operative visual acuity of the surgery group was compared with that of
      the conservatively managed controls. RESULTS: All patients were followed for a
      minimum of 36 months. Mean BCVA (logMAR) in the surgery group changed from 1.10+/
      0.34 to 1.19+/-0.70 and to 0.80+/-0.36 at 12 and 36 months, respectively (p=0.959
      at 12 months, p=0.018 at 36 months). In the control group, visual acuity improved
      from 1.15+/-0.43 to 0.43+/-0.44 and to 0.43+/-0.39 at 12 and 36 months,
      respectively (p=0.015 at 12 months, at p=0.003 at 36 months). A strong trend
      toward better visual acuity at 12 months and final examination was observed for
      controls. (surgery vs. control group, p=0.052 at 12 months, p=0.066 at 36
      months). CONCLUSIONS: Considering the favorable natural course of BVO and the
      unproven effect of reperfusion on macular edema, surgical efficacy of
      arteriovenous adventitial sheathotomy requires further evaluation.

PMID- 18323699
TI  - Pulsatile ocular blood flow in healthy Koreans.
AB  - PURPOSE: To determine the normal reference range of pulsatile ocular blood flow
      (POBF) values in healthy Korean subjects and to find out the factors that may
      affect them. METHODS: A total of 280 eyes of 280 normal subjects were included in
      this study. Best corrected visual acuity (BCVA), intraocular pressure (IOP),
      axial length, POBF, systemic blood pressure, and pulse rate were measured. The
      mean, standard deviation, range, and the 5th and 95th percentiles of POBF were
      calculated, and the influences of various parameters to POBF were determined by
      multiple regression analyses. RESULTS: The mean POBF value was 766.0+/-221.6
      microl/min in men and 1021.1+/-249.5 microl/min in women. The 5th and 95th
      percentiles for POBF values were 486.0 microl/min and 1140.0 microl/min in men
      and 672.0 microl/min and 1458.0 microl/min in women. The POBF values were
      significantly influenced by gender, mean blood pressure, pulse rate, and axial
      length. CONCLUSIONS: Even though the POBF values were influenced by gender, BP,
      and axial length, we could define the normal reference range of POBF in healthy
      Koreans.

PMID- 18323700
TI  - Relationship between the retinal thickness analyzer and the GDx VCC scanning
      laser polarimeter, Stratus OCT optical coherence tomograph, and Heidelberg retina
      tomograph II confocal scanning laser ophthalmoscopy.
AB  - PURPOSE: To assess the relationship between the retinal thickness analyzer (RTA)
      parameters, and those of the GDx VCC scanning laser polarimeter (GDx VCC),
      Stratus OCT optical coherence tomography (Stratus OCT), and Heidelberg retinal
      tomograph II confocal scanning laser ophthalmoscopy (HRT II). METHODS: Twenty
      nine primary open-angle glaucoma patients were retrospectively included in this
      study. Measurements were obtained using the RTA, GDx VCC, Stratus OCT, and HRT
      II. We calculated the correlation coefficients between the parameters of RTA and
      those of the other studies. RESULTS: Among the optic disc parameters of RTA, the
      cup volume was best correlated with Stratus OCT (R=0.780, p<0.001) and HRT II
      (R=0.896, p<0.001). Among the posterior pole retinal thickness parameters, the
      posterior pole abnormally thin area (PPAT) of the RTA and the inferior average of
      the GDx VCC were best correlated (R=-0.596, p=0.001). The PPAT of the RTA and the
      inferior maximum of the Stratus OCT were best correlated (R=-0.489, p=0.006). The
      perifoveal minimum thickness (PFMT) of the RTA and the cup shape measurement of
      the HRT II were best correlated (R=-0.565, p=0.004). CONCLUSIONS: Many RTA optic
      disc parameters were significantly correlated with those of the Stratus OCT and
      HRT II. The RTA posterior pole retinal thickness parameters were significantly
      correlated with those of the GDx VCC, Stratus OCT and HRT II. The RTA optic disc
      and posterior pole retinal thickness parameters may be valuable in the diagnosis
      of glaucoma.

PMID- 18323701
TI  - Relationship between scanning laser polarimetry with enhanced corneal
      compensation and with variable corneal compensation.
AB  - PURPOSE: To evaluate the structure-function relationships between retinal
      sensitivity measured by Humphrey visual field analyzer (HVFA) and the retinal
      nerve fiber layer (RNFL) thickness measured by scanning laser polarimetry (SLP)
      with variable corneal compensation (VCC) and enhanced corneal compensation (ECC)
      in glaucomatous and healthy eyes. METHODS: Fifty-three eyes with an atypical
      birefringence pattern (ABP) based on SLP-VCC (28 glaucomatous eyes and 25 normal
      healthy eyes) were enrolled in this cross-sectional study. RNFL thickness was
      measured by both VCC and ECC techniques, and the visual field was examined by
      HVFA with 24-2 full-threshold program. The relationships between RNFL
      measurements in superior and inferior sectors and corresponding retinal mean
      sensitivity were sought globally and regionally with linear regression analysis
      in each group. Coefficients of the determination were calculated and compared
      between VCC and ECC techniques. RESULTS: In eyes with ABP, R2 values for the
      association between SLP parameters and retinal sensitivity were 0.06-0.16 with
      VCC, whereas they were 0.21-0.48 with ECC. The association of RNFL thickness with
      retinal sensitivity was significantly better with ECC than with VCC in 5 out of 8
      regression models between SLP parameters and HVF parameters (P<0.05).
      CONCLUSIONS: The strength of the structure-function association was higher with
      ECC than with VCC in eyes with ABP, which suggests that the ECC algorithm is a
      better approach for evaluating the structure-function relationship in eyes with
      ABP.

PMID- 18323702
TI  - Outcomes of 6 hour part-time occlusion treatment combined with near activities
      for unilateral amblyopia.
AB  - PURPOSE: To evaluate the outcome of the part-time occlusion therapy with near
      activities in monocular amblyopic patients according to gender, age, severity of
      amblyopia, and the cause of amblyopia. METHODS: Fifty eight patients who were
      prescribed part-time occlusion therapy with near activity from July 1998 to
      October 2004, were included in this retrospective study. All patients were
      divided into groups by gender, age, severity of amblyopia, and the cause of
      amblyopia. Main outcome measures were best corrected visual acuity, line
      improvement, and success rate. RESULTS: At the end of patch therapy, visual
      acuity improved from baseline by an average of 3.2+/-2.5 lines (0.33+/-0.26 log
      MAR), and follow-up period was 19.71+/-14.61 months (1.62+/-1.20 years). At the
      last follow-up, visual acuity improved from baseline by an average of 3.7+/-2.4
      lines (0.38+/-0.26 log MAR), and follow-up period was 37.41+/-25.83 months
      (3.08+/-2.12 years). The success rate was 86% (50 patients) at the end of patch
      therapy. In 44 patients out of 50 patients (88%), the visual acuity was
      maintained. While 43 patients out of 47 patients who were less than 7 years old
      (91%) achieved success, 7 patients out of 11 patients 7 years or older (64%)
      achieved success (p=0.035). CONCLUSIONS: Six-hour part-time occlusion treatment
      combined with near activities appears to be favorable in treating 58 children
      during follow-up of mean 3.08 years. The significant factor was the age at
      initial treatment.

PMID- 18323703
TI  - Results of re-operation on the deviated eye in patients with sensory
      heterotropia.
AB  - PURPOSE: To evaluate the result of re-operation on the deviated eye of recurred,
      consecutive or undercorrected sensory strabismus after surgery. METHODS: The
      medical records of 11 patients who had received second strabismus operation on
      the deviated eye due to recurred, consecutive or undercorrected sensory
      strabismus were studied retrospectively. RESULTS: Among the 11 patients, five
      patients were operated for recurred exotropia after surgery of sensory exotropia
      (group 1), two for consecutive exotropia after surgery of sensory esotropia
      (group 2), and four for undercorrected esotropia after surgery of sensory
      esotropia (group 3). Re-operation was performed 19.2+/-12.6 years after the first
      operation and the mean preoperative deviation before re-operation was 30.0+/-8.66
      prism diopters (PD), 32.5+/-10.6PD, and 32.5+/-8.66PD, respectively. In all
      cases, a small amount of recession or resection compared with the usual surgical
      dosage was applied in re-operation on the deviated eye. The mean follow-up period
      after re-operation was 12.3+/-14.2 (1-48 months). Among the 11 patients,
      postoperative deviations less than 10PD were achieved postoperatively in 8
      (72.7%) at 1 month and of the 8 patients with follow-up data beyond 6 months, 5
      (62.5%) showed orthotropia within 10PD at 6 months or later. CONCLUSIONS: The
      surgical result of re-operation on the deviated eye of recurred, consecutive or
      undercorrected sensory strabismus after the first surgery was satisfactory in
      spite of the reduced amount of surgical correction compared with the surgical
      dosage recommended for the non-operated eye.

PMID- 18323704
TI  - Differences in the histopathology and matrix metalloproteinase expression in
      Tenon's tissue of primary open-angle glaucoma and primary angle-closure glaucoma.
AB  - PURPOSE: To investigate the differences in the histopathology and matrix
      metalloproteinase (MMP) expression in the Tenon's tissue of primary open-angle
      glaucoma (POAG) patients, primary angle-closure glaucoma (PACG) patients, and non
      glaucomatous patients. METHODS: POAG and PACG patients, who underwent a
      trabeculectomy and had no history of ocular disease except glaucoma, were
      enrolled. The number and instillation period of topical eye drops were reviewed.
      For the controls, which were patients without glaucoma or a history of ocular
      surgery, the Tenon's tissue was obtained in the course of retinal detachment
      surgery. For glaucoma patients, the Tenon's tissue was obtained during the
      trabeculectomy. H&E and Masson's trichrome staining and immunohistochemistry for
      MMP-1, MMP-2, and MMP-9 were performed. A total of six eyes of POAG, six eyes of
      PACG, and four control eyes were evaluated. RESULTS: The duration of topical anti
      glaucoma medication and the mean number of anti-glaucoma medications were similar
      in the POAG and PACG groups. The levels of MMP-1 and 2 were elevated in the POAG
      and PACG groups compared to the control group (p=0.03, 0.01, respectively).
      Compared with the control group, the MMP-2 level was higher in the POAG patients
      (p=0.01), whereas the MMP-1 was higher in the PACG patients (p=0.04). The levels
      of MMP-9 in the POAG and PACG patients were not significantly different from that
      of the control patients (p=0.48, 0.26). The levels of MMP-2 were significantly
      lower in the PACG patients than in the POAG patients (p=0.02). CONCLUSIONS: The
      MMP expression was altered in the Tenon's tissue of glaucoma patients compared to
      the control group. The levels of MMP-2 were lower in the PACG patients than in
      the POAG patients. These results suggest that there may be histopathological
      differences in the Tenon's tissue of POAG and PACG patients.

PMID- 18323705
TI  - Case report: femtosecond laser-assisted small incision deep lamellar endothelial
      keratoplasty.
AB  - PURPOSE: To report two cases of femtosecond laser-assisted small incision deep
      lamellar endothelial keratoplasty (DLEK) for patients with corneal endothelial
      decompensation by Fuchs dystrophy and glaucoma METHODS: Femtosecond laser
      (IntraLase; IntraLase Corp., Irvine, CA) with 15 kHz of repetition rate, was used
      for a 9.5 mm diameter by 400 micrometer thickness donor corneal lamellar
      dissection. RESULTS: In Case 1, the graft was clear and compact without interface
      haze, Orbscan showed smooth and regular corneal surface, specular microscopy was
      unremarkable without sign of corneal endothelial damage, and Optical coherence
      tomography showed uniform graft well attached to recipient stroma with minimal
      interface reflection at 2 months postoperation. In Case 2, the graft was clear
      and compact with minimal interface haze at 1 month postoperation. Femtosecond
      laser-assisted small incision DLEK was safe and technically feasible in our
      cases; however, further evaluation is required to determine long-term effects.

PMID- 18323706
TI  - Experience of Comamonas acidovorans keratitis with delayed onset and treatment
      response in immunocompromised cornea.
AB  - PURPOSE: To report 2 cases of Comamonas acidovorans keratitis in
      immunocompromised cornea. METHODS: A complete review of the medical records of
      the two cases of Comamonas acidovorans keratitis. RESULTS: We found some
      similarities in clinical courses of two cases. Both of them showed development of
      keratitis during the management with corticosteroids, delayed onset, slow
      response to antibiotics, and relatively less affected corneal epithelium.
      CONCLUSIONS: Comamonas acidovorans is known as a less virulent organism. However
      it can cause an indolent infection that responds slowly even to adequate
      antibiotics therapy in immunocompromised corneas.

PMID- 18323707
TI  - A case report on the change of the refractive power after a blunt trauma.
AB  - PURPOSE: To determine the pathogenesis of transient myopia after blunt eye
      trauma. METHODS: In one patient, the refraction of both eyes (the left eye was
      injured, but the right eye was not) was measured with an autorefractometer. The
      cycloplegic refraction was measured at the early stage of trauma and again 3
      months after the blunt eye injury. The angle and depth of the anterior chamber,
      the ciliary body, and the choroids were examined by ultrasound biomicroscopy
      (UBM) over 3 months. The depth of the anterior chamber, the thickness of the
      lens, and the axial length were measured by A-scan ultrasonography in both eyes.
      During the 3 months after the injury, we made comparisons between the menifest
      and the cycloplegic refractions, the depths of anterior chambers, the thickness
      of the lenses, the axial lengths, and the UBM-determined appearances of the
      angles and depths of the anterior chambers, the ciliary bodies, and the choroids
      in both eyes. RESULTS: We suspect that the depth reduction in the anterior
      chamber, the increase in anterior to posterior lens diameter, and the edema in
      the ciliary body are all related to the change in the refractive power following
      the blunt trauma. CONCLUSIONS: Ultrasound biomicroscopy (UBM) and ultrasonography
      of the anterior segment in the eye may be helpful to diagnose and confirm changes
      in the refractive power that occur after trauma.

PMID- 18323708
TI  - A case of cataract surgery without pupillary device in the eye with iridoschisis.
AB  - PURPOSE: To introduce a case of iridoschisis patient who underwent cataract
      surgery successfully without pupil device. METHODS: A 64-year-old female who
      showed iridoschisis of her both eyes underwent cataract operation at her right
      eye without a pupillary device. The preoperative and postoperative ophthalmologic
      examinations including visual acuity, intraocular pressure, reaction of anterior
      chamber, and degree of damage on iris was evaluated respectively. RESULTS:
      Cataract surgery was performed under topical anesthesia through a clear corneal
      incision. Iris fibrils were held in place by ophthalmic viscosurgical device
      (OVD, sodium hyaluronate 3%-sodium chondroitin sulfate 4%, Viscoat) that was
      injected into the anterior chamber. A small capsulorrhexis was made and the
      nucleus was delivered with low-power phacoemulsification, most of which was
      performed under the anterior capsule. The iris came into contact with the OVDs
      only and received no mechanical trauma. There were no intraoperative
      complications such as tear of the iris, hyphema, loss of mydriasis, or rupture of
      the posterior lens capsule. The edema of corneal stroma and inflammation of
      anterior chamber was shown at immediate-postoperative period, but completely
      subsided 2 weeks later. The visual acuity showed improvement from 20/400 to
      20/30. CONCLUSIONS: In iridoschisis patients, there is a risk of aspiration of
      iris fibers during cataract surgery. With adequate use of OVD and careful
      modulation of surgical devices, cataract surgery was successfully performed
      without using extra pupil-supporting device.

PMID- 18323709
TI  - A case of postoperative Sphingomonas paucimobilis endophthalmitis after cataract
      extraction.
AB  - PURPOSE: To report a case of an acute onset of delayed postoperative
      endophthalmitis that was caused by Sphingomonas paucimobilis. METHODS: This case
      demonstrates an acute onset of delayed postoperative endophthalmitis at 3 months
      after uneventful cataract extraction and posterior chamber intraocular lens
      implantation. We performed vitrectomy, intraocular lens and capsular bag removal,
      and intravitreal antibiotics injection. On the smear stains from the aspirated
      vitreous humor, gram-negative bacilli were detected and S. paucimobilis was found
      in culture. RESULTS: At three months after vitrectomy, the best corrected visual
      acuity was 20/300. Fundus examination showed mild pale color of optic disc and
      macular degeneration. CONCLUSIONS: Vitrectomy with intravitreal ceftazidime
      injection had contributed to the favorable result in case of an acute onset of
      delayed postoperatire endophthalmitis caused by S. paucimobilis.

PMID- 18323710
TI  - Bilateral ophthalmic artery occlusion in rhino-orbito-cerebral mucormycosis.
AB  - PURPOSE: To report a case of bilateral ophthalmic artery occlusion in rhino
      orbito-cerebral mucormycosis. METHODS: Reviewed clinical charts, photographs, and
      fluorescein angiography RESULTS: An 89-year-old man with poorly controlled
      diabetes developed sudden bilateral ptosis, complete ophthalmoplegia of the right
      eye, and superior rectus palsy of the left eye. Brain and orbit magnetic
      resonance imaging showed midbrain infarction and mild diffuse sinusitis. On the
      2nd day of hospitalization, sudden visual loss and light reflex loss developed.
      There were retinal whitening, absence of retinal arterial filling, and a total
      lack of choroidal perfusion on fluorescein angiography of the right eye. The left
      eye showed a cherry red spot in the retina and the absence of retinal arterial
      filling and partial choroidal perfusion on fluorescein angiography. On rhinologic
      examination, mucormyosis was noticed. Despite treatment, visual acuity and light
      reflex did not recover and he died 4 days after admission. CONCLUSIONS: Bilateral
      ophthalmic artery occlusion can occur in rhino-orbital-cerebral mucormycosis.

PMID- 18323711
TI  - Retinal artery occlusion in a healthy pregnant patient.
AB  - PURPOSE: We report a case of branch retinal artery occlusion (BRAO) in a healthy
      pregnant woman. METHODS: A 29-year-old pregnant woman presented with decreased
      vision in her left eye. She had a pale retina with macular edema consistent with
      BRAO. An extensive workup was performed to determine an etiologic factor. All
      test results were within normal limits except for her factor VIII activity. Her
      visual acuity improved from finger counting to 20/30 over 2 months without any
      treatment. RESULTS: This case suggests that BRAO can occur in healthy patients
      without any systemic or ocular disorders. CONCLUSIONS: BRAO can occur in healthy
      patients without any systemic or ocular disorders, despite an extensile
      evaluation.

PMID- 18323712
TI  - [Evaluation of cognitive functions, depression, life satisfaction among the
      elderly receiving visiting nursing services].
AB  - PURPOSE: The purpose of this study was to examine cognitive functions,
      depression, and life satisfaction among the elderly receiving visiting nursing
      services. METHODS: The subjects of this study consisted of 221 elderly
      individuals who were receiving visiting nursing services from a public health
      center located in Gyeonggi-do. The Mini-mental State Examination Korea version
      (MMSE-K), Geriatric Depression Scale-short form-Korea version (GDS-K), and Life
      Satisfaction Scale were utilized to determine cognitive functions, depression,
      and life satisfaction. Collected data was analyzed by the SPSS PC Win 12.0
      program. RESULTS: The prevalence of cognitive impairment (MMSE-K <or= 24) was
      86.4%, and the proportion of severe depression (GDS-K >or= 10) was 22.6%. Older
      age, lower education, and low income were associated with cognitive impairment,
      and low education, no religion, and low income were associated with depression.
      Cognitive function negatively correlated with depression. Life satisfaction level
      was fairly low and was not associated with any variables. CONCLUSION: The high
      prevalence of cognitive impairment and low life satisfaction status were
      determined among low-income elderly who were registered at a visiting health care
      center. Thus, in the future at visiting health care services, efficient and
      various programs for the elderly should be tried, to improve cognitive functions
      and reduce depression. Additionally, consistent evaluation studies for those
      programs will be required.

PMID- 18323713
TI  - [Effects of Tai Chi exercise in elderly with knee osteoarthritis].
AB  - PURPOSE: This study was to determine whether the Sun-style 24 forms of Tai Chi
      exercise improve pain, stiffness, disability, knee joint motion, mobility,
      balance or falling. METHOD: Forty-six community-dwelling elderly subjects (mean
      age, 75.46+/-6.28) voluntarily participated in an intervention group of either 24
      forms of Sun-style Tai Chi for 60 min, 2 times per week for 12 weeks or a control
      group. A non-equivalent pretest-posttest design was used. Independent t-test and
      ANCOVA were used to examine group differences by using SPSS12.0. RESULT: The
      experimental group had significantly less pain (F=7.60, p=.008) and stiffness (t=
      3.19, p=.003) than the control group. Also there were significant improvements in
      knee joint motion on the right knee (t=2.44, p=.019), left knee (t=2.30, p=.026),
      rising time (F=8.03, p=.07), balance on the left single leg test (t=2.20,
      p=.033), and fear of falling (t=-2.33, p=.024) in the Tai Chi exercise group. No
      significant group differences were found in disability and falls efficacy.
      CONCLUSION: The Sun-style 24 forms Tai Chi exercise is effective in decreasing
      pain, stiffness, fear of falling and it improves balance, rising time, and knee
      joint motion. We suggest a continuing long term intervention to decrease
      disability and increase efficacy concerning falls.

PMID- 18323714
TI  - [The analysis of type D personality research as a psychosocial risk factor in
      cardiovascular disease for elders with a chronic disease].
AB  - PURPOSE: The purpose of this paper was to examine the relationship between type D
      personality and cardiovascular disease, and to suggest future research
      directions. METHOD: A literature search was conducted from the following nine
      databases: 1) MEDLINE, 2) CINAHL, 3) Pubmed Unrestricted, 4) PsycINFO, 5) KISS,
      6) RICHIS, 7) RISS4U, and 8) Nanet. The combinations of the words, "type D
      personality", "personality", "heart", "cardiovascular", and "coronary" were used
      for keyword searches to find relevant articles. Twenty eight studies were
      identified. RESULT: Type D personality has been associated with increased
      morbidity and mortality in patients with established cardiovascular disease. Type
      D patients are also at increased risk for impaired quality of life, and seem to
      benefit less from medical and invasive treatment. CONCLUSION: There is
      substantial evidence for a relationship between type D personality and clinical
      outcomes related to cardiovascular disease. Randomized clinical trials are needed
      to further evaluate the value of controlling type D personality to improve
      survival and reduce morbidity in patients with cardiovascular disease.
      Accumulating evidence from this analysis indicates the urgent need to adopt a
      personality approach in order to optimize the identification of patients at risk
      for stress related cardiac events.

PMID- 18323715
TI  - [Wandering behavior in Korean elders with dementia residing in nursing homes].
AB  - PURPOSE: This study investigated various factors related to wandering behavior of
      Korean elders with dementia (KED). METHODS: A sample of 160 ambulatory residents
      with dementia from 14 long term care facilities was used to examine demographic,
      individual, cognitive, physical health, and environmental characteristics by
      comparing wanderers (N=108) to nonwanders (N=52). Subjects were evaluated by
      Korean versions of the Mini-mental State Exam (K-MMSE), the Physical and
      Instrumental Activities of Daily Living (K-PIADL), and the Revised Algase
      Wandering Scale Nursing Home version (KRAWS-NH) along its six dimensions.
      Demographic and environmental data were also obtained. Independent sample t
      tests, Chi-square test, Fisher's Exact tests, and ANCOVAs were used to examine
      differences between wanderers and nonwanders. RESULTS: Wanderers were
      significantly (p<.05) older and had more limitations in K-PADL and K-IADL. The
      degree of overall wandering and certain features of wandering were significantly
      different (p<.05) by total number of residents in the facility, type of bedroom
      (i.e., "Ondol"), and color of bedroom and living-room walls (i.e., sky blue).
      CONCLUSIONS: Findings of this study may be useful in understanding wandering
      behavior of KEDs and thus developing more culturally specific management
      strategies.

PMID- 18323716
TI  - [Evaluation of a waterless, scrubless chlorhexidine gluconate/ethanol surgical
      scrub and povidone-iodine for antimicrobial efficacy].
AB  - PURPOSE: The purpose of this study was to compare 1% chlorhexidine-gluconate/61%
      ethanol (CHG/Ethanol) emollient and 7.5% povidone-iodine (PVI) scrub for
      antimicrobial,residual effect, and skin condition. METHOD: CHG/Ethanol emollient
      hand hygiene was performed waterless, and brushless by operating doctors and
      nurses (N=20). PVI hand washing was performed with water and a brush (N=20) for 5
      min. The subjects were asked to press their left hand in hand-shaped agar before
      a surgical scrub, immediately after a surgical scrub and after the operation. The
      amount of isolated microorganisms were calculated by counting the number of
      divided areas(1 x 1 cm, 160 cell) which were culture positive in the hand culture
      plate. The skin condition was evaluated. RESULT: The antimicrobial count of
      CHG/Ethanol emollient and PVI immediately post surgical scrub was 0.0 vs. 4.1
      (p>.05), and after the operation was 0.1 vs. 37.8 (p>.05)respectively. The
      Residual effect of CHG/Ethanol emollient immediately post surgical scrub and
      after the operation were 0.0 vs. 0.1 (p>.05), and PVI were 4.1 vs. 37.8
      (p>.05)respectively. The skin condition and satisfaction of CHG/Ethanol emollient
      was higher than PVI (p<.05). CONCLUSION: The antimicrobial effect between
      CHG/Ethanol emollient and PVI were the same. Considering skin condition,
      satisfaction and allergic reaction CHG/Ethanol emollient for surgical scrub is
      recommended in Korea.

PMID- 18323717
TI  - [Balanced scorecard for performance measurement of a nursing organization in a
      Korean hospital].
AB  - PURPOSE: The purpose of this study was to develop a balanced scorecard (BSC) for
      performance measurement of a Korean hospital nursing organization and to evaluate
      the validity and reliability of performance measurement indicators. METHOD: Two
      hundred fifty-nine nurses in a Korean hospital participated in a survey
      questionnaire that included 29-item performance evaluation indicators developed
      by investigators of this study based on the Kaplan and Norton's BSC (1992).
      Cronbach's alpha was used to test the reliability of the BSC. Exploratory and
      confirmatory factor analysis with a structure equation model (SEM) was applied to
      assess the construct validity of the BSC. RESULT: Cronbach's alpha of 29 items
      was .948. Factor analysis of the BSC showed 5 principal components (eigen value
      >1.0) which explained 62.7% of the total variance, and it included a new one,
      community service. The SEM analysis results showed that 5 components were
      significant for the hospital BSC tool. CONCLUSION: High degree of reliability and
      validity of this BSC suggests that it may be used for performance measurements of
      a Korean hospital nursing organization. Future studies may consider including a
      balanced number of nurse managers and staff nurses in the study. Further data
      analysis on the relationships among factors is recommended.

PMID- 18323718
TI  - [The relationship between eating disorders and parent-adolescent communication in
      middle school students in rural areas].
AB  - PURPOSE: The purpose of this study was to examine the relationship between eating
      disorders and parent-adolescent communication in middle school students. METHOD:
      There were 267 adolescents taken as participants from two middle schools in rural
      areas. Data were collected from June to July 2005, using the Eating Disorder
      Inventory-2 questionnaire (23 items) and Parent-Adolescent Communication
      Inventory (10 items for open family communication, 10 items for problem in family
      communication). The SPSS Win version 12.0 was used for descriptive analysis, t
      test, and partial correlation coefficient. RESULT: The mean score on the eating
      disorder was 2.74 (range: 1-6). Meanwhile, the mean scores on the parent
      adolescent communication was 3.37 (range: 1-5). There were significant
      differences in eating disorders according to gender, age, negative perception of
      the participant's body weight, family's perception of obesity, diet experiences,
      and BMI. Eating disorders showed a significant negative correlation with parent
      adolescent communication. CONCLUSION: In this study, there was a significant
      negative correlation between eating disorders and parent-adolescent
      communication. In order to prevent an eating disorder, education and training to
      enhance communication skills should be provided to adolescents and their parents
      as well.

PMID- 18323719
TI  - [Effects of the nutrition education program on self-efficacy, diet behavior
      pattern and cardiovascular risk factors for the patients with cardiovascular
      disease].
AB  - PURPOSE: This study examined the effects of a nutrition education program on self
      efficacy, diet behavior pattern and cardiovascular risk factors for patients with
      cardiovascular disease (CVD). METHOD: Sixty-four CVD subjects (37 experimental,
      27 control) were recruited from a cardiac center, at a university hospital
      located in D city, Korea. All subjects attended a first heart camp where pretest
      measures were performed, and a second heart camp at 6 months for the posttest
      measures. During the 6 month study period, the experimental group was required to
      attend five monthly nutrition education sessions, while the control group
      received only routine outpatient follow-ups. Data were analyzed by chi(2)-test
      and independent t-test using the SPSSWIN 11.5 program. RESULT: Group comparisons
      revealed that the experimental group had significantly more improved self
      efficacy, frequency of food selection, gustation of salt, systolic blood
      pressure, and serum total-cholesterol compared to the control group. CONCLUSION:
      A nutrition education program may be effective in improving self-efficacy, diet
      behavior pattern and cardiovascular risk factors for patients with cardiovascular
      disease.

PMID- 18323720
TI  - [Trends of doctoral dissertations in nursing science: focused on studies
      submitted since 2000].
AB  - PURPOSE: The purpose of this study was to identify the characteristics of
      doctoral dissertations in nursing science submitted since 2000. METHOD: Three
      hundred and five dissertations of six schools of nursing published from 2000 to
      2006 in Korea were analyzed with the categories of philosophy, method, body of
      knowledge, research design, and nursing domain. RESULT: In philosophy, 82% of all
      dissertations were identified as scientific realism, 15% were relativism, and 3%
      were practicism. Two-hundred and fifty dissertations (82%) were divided into a
      quantitative methodology and 55 dissertations (18%) were qualitative methodology.
      Specifically, 45% were experimental, 23% methodological, 13% survey and 17%
      qualitative designed researches. Prescriptive knowledge was created in 47% of
      dissertations, explanatory knowledge in 29%, and descriptive knowledge in 24%.
      Over 50% of all research was studied with a community-based population. In the
      nursing domain, dissertations of the practice domain were highest (48.2%).
      CONCLUSION: Dissertations since 2000 were markedly different from the
      characteristics of the previous studies (1982-1999) in the increase of situation
      related, prescriptive and community-based population studies. A picture of
      current nursing science identified in this study may provide a future guideline
      for the doctoral education for nursing.

PMID- 18323721
TI  - [Validity and reliability of a clinical performance examination using
      standardized patients].
AB  - PURPOSE: The purpose of this study was to test the validity of a modified
      clinical performance examination (CPX) for preclinical students in nursing.
      METHOD: 70 nursing students in their second semester of the junior year at C
      University participated in CPX. Scenarios and checklists were developed by our
      research team from September to October 2005. Six stations were organized.
      Evaluation included physical examination of a patient with lung cancer, education
      on usage of a metered dosage inhaler, and lobectomy postoperative care. Students
      were randomly assigned to a station. RESULT: There was a difference in the CPX
      scores according to stations. The agreement of scoring between trained faculty
      members and SPs was more than moderate (r=.647). The correlation between the CPX
      score and the average grade in the previous semester and between the CPX score
      and the average grade of a paper and pen test of the pulmonary system of adults
      was low (r=.276; r=.048). CONCLUSION: Traditional CPX is generally recommended,
      however, modified CPX is appropriate for preclinical students in the current
      Korean Nursing school setting if there are additional scoring systems to balance
      the testing level at each station.

PMID- 18323722
TI  - [Prevalence rate and associated factors of urinary incontinence among nursing
      home residents].
AB  - PURPOSE: The aim of this study was to estimate the prevalence of urinary
      incontinence among nursing home residents and to identify the factors associated
      with this condition. METHOD: The data were collected from 618 subjects (146 males
      and 472 females; mean age 79.9+/-8.4 yr; range 65-102 yr) of 30 nursing homes in
      Seoul, Gyeonggi-do and Gangwon-do in this cross-sectional study. The data were
      analyzed by chi-square test, t-test, and multiple logistic regression by using
      the SPSS/PC ver 12.0 program. RESULTS: The prevalence of UI was 64.7% (64.6% in
      women; 65.1% in men). After adjustment for each of the variables considered in
      this study, six potential factors were strongly associated with UI: activities of
      daily living, comorbidity, age, cognition, specialty of the facility, and a
      bladder training program. CONCLUSION: Our finding suggests that it is necessary
      to develop a program for promotion of activities of daily living and to provide a
      bladder training program to prevent urinary incontinence among nursing home
      residents.

PMID- 18323723
TI  - [A study on exercise behavior, exercise environment and social support of middle
      aged women].
AB  - PURPOSE: The purpose of this study was to identify exercise environments and
      social support associated with exercise behaviors in middle-aged women. METHOD:
      Subjects were 207 women aged between 41 and 59 yr in an urban community. The
      research instruments utilized in this study were exercise stages, exercise
      environments, exercise partners and social support scale. Subjects were given a
      self-report questionnaire. Data was analyzed using the SPSS Win program. RESULT:
      The subjects were in the stages of precontemplation (3.4%), contemplation
      (25.1%), preparation (40.6%), action (5.8%), and maintenance (25.1%). Subjects
      who engaged in regular exercise were 30.9%. The mean score of the exercise
      environment was 6.34. The mean score of social support was 21.28, and 65.7% of
      subjects had exercise partners. The score of the exercise environment was
      significantly associated with the exercise stage (p=.01). The number of exercise
      partners of regular exercise groups was significantly greater than that of non
      regular exercise groups (p=.00). The score of social support of regular exercise
      groups was significantly greater than that of non-regular exercise groups
      (p=.00). The score of social support was significantly associated with the
      exercise stage (p=.00). CONCLUSION: Exercise environments and social support need
      to be considered in planning exercise programs to improve exercise behavior among
      middle-aged women.

PMID- 18323724
TI  - [Types of attitudes toward a successful life of Korean nursing students: a Q
      methodological approach].
AB  - PURPOSE: The purpose of this study was to analyze attitudes toward a successful
      life of students majoring in nursing science. METHOD: The Q-methodology which
      provides a method of analyzing the subjectivity of each items was used. The 32
      selected Q-statements from each of 36 subjects were classified into a shape of
      normal distribution using a 9 point scale. The collected data was analyzed using
      a QUANL PC program. RESULT: Four types of successful life attitudes for research
      subjects in nursing science were identified. Type I is purpose achievement type,
      Type II is calling fullness type, Type III is balance maintenance type, and Type
      IV is happiness eagerness type. CONCLUSION: The results of the study indicate
      that different approaches to nursing professional education programs are
      recommended based on the four types of successful life attitudes.

PMID- 18323725
TI  - [The relationship of perceived health status, activities of daily living and
      nutrition status in the community-dwelling Korean elderly].
AB  - PURPOSE: This study aimed to identify the associated factors of the perceived
      health status of the elderly in Korea and to provide basic data for developing
      nursing interventions for the elderly's health management. METHODS: This study
      used a descriptive correlational research design. The subjects of this study were
      335 elderly people over 60 yr living in an urban city. Data were collected
      through personal interviews using questionnaires from September 2006 to March
      2007. Empirical indicators of perceived health status were measured by SF-36,
      nutritional screening initiative (NSI), activities of daily living (ADL) Index,
      and instrumental activities of daily living (IADL) scale. The collected data were
      analyzed by descriptive statistics, Pearson's correlation, and hierarchical
      regression. RESULTS: The mean age of the subjects was 72.8 and 57.0% of subjects
      were female. 41.5% of variance in physical health was explained by nutrition,
      ADL, IADL, and the number of years attending school. Among them the most
      important factor was ADL. 13.2% of variance in mental health was explained by the
      number of family, nutrition, and IADL. Among them the most important factor was
      nutrition. CONCLUSION: It is necessary to develop supportive interventions for
      improving the perceived health status of elderly people by considering the most
      important factors shown in this study.

PMID- 18323726
TI  - [The effects of meridian massage on menopausal symptoms and Shin-Hur in middle
      aged menopausal women].
AB  - PURPOSE: The purpose of this study was to identify the effects of meridian
      massage on menopausal symptoms and Shin-Hur in middle-aged menopausal women.
      METHOD: The research design was a nonequivalent control group pre-post
      experimental design. The subjects of the study were middle-aged women who had had
      no menstruation in the last 12 months after the last menstrual bleeding. Cards of
      invitation on bulletin boards of several apartments were placed to recruit the
      subjects. The cards of invitation included: purpose of the study, eligibility
      criteria, method and period. Eighteen women in the experimental group and 16
      women in the control group were conveniently assigned, respectively. The
      experimental group received 20 min meridian massage 3 times per week for 4 weeks.
      The menopausal symptoms and Shin-Hur were measured and compared between the two
      groups before and after the intervention. Data were analyzed with the SPSS
      program by Fisher's exact test, Wilcoxon Sign Rank test, Mann Whitney U-test and
      Spearman's rank correlation. RESULT: The experimental group showed a significant
      decrease of menopausal symptoms (U=77.00, p=.020) and Shin-Hur (U=76.00, p=.017).
      There was a significantly positive correlation between menopausal symptoms and
      Shin-Hur (r=.497, p=.003). CONCLUSION: Meridian massage was effective in
      improving menopausal symptoms and Shin-Hur in middle-aged menopausal women. Thus
      it can be useful as a nursing intervention for menopausal women.

PMID- 18323727
TI  - [The actual experiences of the living world among cancer patients].
AB  - PURPOSE: The purpose of this study was to understand the meanings and nature of
      living in the world among cancer patients. The present study adopted a
      hermeneutic phenomenological method which was developed by van Manen. METHOD: The
      participants for this study were 5 men and 6 women, who were over the age of 20
      with admission or a follow up visit in the medical or surgical department. Data
      were collected by using in-depth interviews and observations from February to
      September, 2007. The contents of the interviews were tape-recorded with the
      consent of the subject. RESULT: The essential themes that fit into the context of
      the 4 existential grounds of body, time, space and other people were: a body that
      cannot be restored, a body that endures and lives, waiting in uncertainty, a
      valued calculation for the living day, being in a world of invisible power,
      reestablishing relationships, and reflection on his or her life. CONCLUSION:
      These findings revealed that living in the world is affected to varying degrees
      by the cancer. It is important for nurses to identify and take care of
      disabilities and to support the reorientation in the disintegrated life
      situation. The result of this study can give nurses some insight into these
      experiences and help promote empathetic care.

PMID- 18323728
TI  - [Development and evaluation of an e-learning program for mothers of premature
      infants].
AB  - PURPOSE: It has been attempted to support mother of premature infants by
      providing information of premature infant care using e-learning because premature
      infants need continuous care from birth to after discharge. METHOD: The e
      Learning Program for mother of premature was developed with Xpert, Namo web
      editor, Adobe Photoshop, and PowerPoint and applied for 4 weeks from 4 to 30
      September 2006. RESULT: 1) We found that the contents of information which
      premature infants' need when being in the hospital and after discharge were the
      definition of a premature infant, orientation of NICU, care of premature infants,
      care of premature infants' common diseases, the connection of healthcare
      resources, exchange of information, and the management of rearing stress. 2) The
      program content consisted of cause of premature birth, comparison to full-term
      baby, physiology character, orientation of NICU, common health problems, follow
      up care, infection control, feeding, normal development physically and mentally,
      weaning method, and vaccination. CONCLUSION: Considering the results, this
      program for mother of premature is a useful means to provide premature-care
      information to mothers. This information can be readily accessible and can be
      varied and complex enough to be able to help mothers to the information and
      assistance they require.

PMID- 18323729
TI  - [An analysis of cost and profit of a nursing unit using performance-based
      costing: case of a general surgical ward in a general hospital].
AB  - PURPOSE: The aim of this study was to analyze net income of a surgical nursing
      ward in a general hospital. METHOD: Data collection and analysis was conducted
      using a performance-based costing and activity-based costing method. RESULT:
      Direct nursing activities in the surgical ward were 68, indirect nursing
      activities were 10. The total cost volume of the surgical ward was calculated at
      won 119,913,334.5. The cost volume of the allocated medical department was won
      91,588,200.3, and the ward consumed cost was won 28,325,134.2. The revenue of the
      surgical nursing ward was won 33,269,925.0. The expense of a surgical nursing
      ward was 28,325,134.2. Therefore, the net income of a surgical nursing ward was
      won 4,944,790.8. CONCLUSION: We suggest that to develop a more refined nursing
      cost calculation model, a standard nursing cost calculation system needs to be
      developed.

PMID- 18323730
TI  - [Effect of postpartum breast-feeding support by nurse on the breast-feeding
      prevalence].
AB  - PURPOSE: The purpose of this study was to investigate the effects of the
      professional nurse's postpartum breast-feeding support on breast-feeding
      prevalence for mothers who delivered in Baby-Friendly Hospitals (BFH). METHODS:
      This quasi experimental study was designed with a nonequivalent control group
      post test. The subjects of this study were 55 mothers who were hospitalized in
      the delivery room of a university hospital which was selected as a BFH in Daegu
      from October 1, 2005 to June 30, 2006. Twenty nine mothers were assigned to the
      experimental group and 26 mothers to the control group. Postpartum breast-feeding
      support by nurses' telephone calls to the experimental group was provided once a
      week for 4 weeks postpartum and then once a month for 16 weeks postpartum. Four
      post tests were given at postpartum week 4, 8, 12, and 16. The control group was
      given a telephone call at postpartum week 4, 8, 12, and 16. RESULTS: The
      breastfeeding prevalence of the experimental group was significantly higher than
      that of the control group for each period. CONCLUSION: Postpartum breast-feeding
      support by nurses may be a useful intervention to increase breast-feeding
      prevalence.

PMID- 18323731
TI  - [Accuracy of references in eight nursing journals in Korea].
AB  - PURPOSE: This study was to investigate the reference accuracy in major nursing
      journals in Korea. METHODS: The references in articles from eight nursing
      journals from 2006 were compared with PubMed for authors, year, title, journal,
      volume, and page accuracy. Four hundred sixty-six references were reviewed.
      Errors were classified as major or minor and categorized by bibliographic
      headings (author, title, journal, year, volume and page). RESULTS: Of the 466
      references, 223(47.9%) had citation errors. The reference error rates ranged from
      28.6% to 58.7%. Most errors occurred in the author element (37.9%), followed by
      title (20.9%), journal (19.0%), page (13.9%), volume (5.9%), and year (2.4%).
      CONCLUSION: This study identified a considerable error rate in the references of
      nursing journals. Inaccuracy of references is a reflection on scholarly work of
      authors and journals. Authors and Editorial committees are responsible for the
      accuracy of references.

PMID- 18323732
TI  - Reduced cytokine production by glycogen-elicited peritoneal cells from diabetic
      rats.
AB  - IL-1beta, TNF-alpha, cytokine-induced neutrophil chemoattractant-2alpha/beta, and
      IL-10 measurements were performed in elicited peritoneal cells from control,
      diabetic, and insulin-treated diabetic rats. Production/liberation of these
      cytokines was decreased in elicited peritoneal cells from diabetic rats. These
      changes were abolished by insulin treatment of diabetic rats. The alterations
      observed might be involved in the impaired inflammatory response and high
      occurrence of apoptosis observed in neutrophils under diabetic states.

PMID- 18323733
TI  - Proestrus female rats are more resistant to right ventricular pressure overload.
AB  - Multiple studies of left ventricular dysfunction suggest that females may be more
      resistant to ischemia or endotoxemia. However, sex differences in right
      ventricular (RV) responses to pressure overload and/or endotoxemia have not been
      elucidated. We hypothesized that females would maintain better RV function during
      acute pressure overload (APO), endotoxemia, or a simultaneous insult from both
      processes. Age-matched male and proestrus female Sprague-Dawley rats were given
      an intraperitoneal injection of either phosphate buffered saline or LPS. Six
      hours after injection, hearts were removed by median sternotomy and isolated via
      Langendorff. End-diastolic pressures were sequentially elevated past physiologic
      levels by increasing the volume of a latex balloon that was inserted into the RV.
      Male RV function was depressed to a greater degree after APO injury compared with
      that in females (developed pressure: male, 44.97 mmHg vs. female, 58.23 mmHg).
      Interestingly though, at a physiologic end-diastolic pressure of 5 mmHg,
      endotoxic males and females maintained equivalent RV function. However, with
      concurrent endotoxic insult and APO, RV function was better maintained in males
      as compared with that in females (developed pressure: male, 59% of control versus
      female, 41% of control). Furthermore, tissue levels of IL-1 and IL-6, but not IL
      10, were increased after endotoxin exposure but did not differ based on sex.
      Through this study, we have shown that sex differences exist in RV dysfunction,
      and that different cardiac insults diversely affect myocardial function.
      Understanding these differences may allow for the implementation of novel
      therapeutic treatment options that are designed to attenuate RV cardiovascular
      collapse.

PMID- 18323734
TI  - Treatment with the glycogen synthase kinase-3beta inhibitor, TDZD-8, affects
      transient cerebral ischemia/reperfusion injury in the rat hippocampus.
AB  - The serine/threonine glycogen synthase kinase 3beta (GSK-3beta) is abundant in
      the central nervous system, particularly in the hippocampus, and plays a pivotal
      role in the pathophysiology of a number of diseases, including neurodegeneration.
      This study was designed to investigate the effects of GSK-3beta inhibition
      against I/R injury in the rat hippocampus. Transient cerebral ischemia (30 min)
      followed by 1 h of reperfusion significantly increased generation of reactive
      oxygen species and modulated superoxide dismutase activity; 24 h of reperfusion
      evoked apoptosis (determined as mitochondrial cytochrome c release and Bcl-2 and
      caspase-9 expression), resulted in high plasma levels of TNF-alpha and increased
      expression of cyclooxygenase-2, inducible nitric oxide synthase, and
      intercellular adhesion molecule-1. The selective GSK-3beta inhibitor, 4-benzyl-2
      methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8), was administered before and
      after ischemia or during reperfusion alone to assess its potential as
      prophylactic or therapeutic strategy. Prophylactic or therapeutic administration
      of TDZD-8 caused the phosphorylation (Ser(9)) and hence inactivation of GSK
      3beta. Infarct volume and levels of S100B protein, a marker of cerebral injury,
      were reduced by TDZD-8. This was associated with a significant reduction in
      markers of oxidative stress, apoptosis, and the inflammatory response resulting
      from cerebral I/R. These beneficial effects were associated with a reduction of
      I/R-induced activation of the mitogen-activated protein kinases JNK1/2 and p38
      and nuclear factor-kappaB. The present study demonstrates that TDZD-8 protects
      the brain against I/R injury by inhibiting GSK-3beta activity. Collectively, our
      data may contribute to focus the role of GSK-3beta in cerebral I/R.

PMID- 18323735
TI  - The effect of dobutamine on platelet aggregatory function in newborn piglets with
      hypoxia and reoxygenation.
AB  - Dobutamine, a beta-adrenoceptor agonist that is often used to treat myocardial
      dysfunction in asphyxiated neonates, may act on the adrenoceptors of platelets
      resulting in activation. Little information is available on the effect and
      mechanistic pathway of dobutamine on the platelet aggregatory function in
      neonatal asphyxia. Newborn piglets were acutely instrumented and exposed to
      hypoxia for 2 h and reoxygenation for 4 h. Piglets were randomized to receive
      dobutamine infusion (5, 10, or 20 microg/kg per min) or saline (hypoxic-control)
      at 2 to 4 h of reoxygenation (n = 8 each), and sham-operated animals were not
      exposed to hypoxia and reoxygenation (n = 6). Platelet number, collagen
      stimulated whole blood aggregation, and plasma concentrations of thromboxane B2
      were studied. The effects of alpha- and beta-adrenoceptor antagonists
      (phentolamine and propranolol, respectively) on platelet aggregation to in vitro
      administration of dobutamine (3 microM) were also examined. Shock and metabolic
      acidosis developed similarly in all hypoxia-reoxygenated groups. At 4 h of
      reoxygenation, platelet numbers in all groups decreased, with no differences
      among groups. Platelet aggregation deteriorated significantly with a rightward
      shift of concentration-response curve in piglets receiving 10 and 20 microg/kg
      per min of dobutamine. The group that received 20 microg/kg per min of dobutamine
      had increased plasma thromboxane B2 concentrations from baseline (P < 0.05). The
      platelet aggregatory response induced by 3 microM of dobutamine was improved by
      the coadministration of the beta-but not the alpha-adrenoceptor antagonist. We
      observed platelet aggregatory dysfunction in hypoxic-reoxygenated newborn piglets
      treated with high-dose dobutamine. Further investigation is needed to examine the
      differential effects of dobutamine and hypoxia-reoxygenation in platelet
      aggregation in newborns.

PMID- 18323736
TI  - Heart rate multiscale entropy at three hours predicts hospital mortality in 3,154
      trauma patients.
AB  - Complexity is a measure of variation and randomness potentially indicating
      improvement or deterioration in critically ill patients. Previously, we have
      shown integer heart rate (HR) multiscale entropy (MSE), an indicator of
      complexity, predicts death based on long duration (12 h) and dense (>or=0.4 Hz)
      windows of HR data. However, such restrictions reduce the use of MSE in the
      clinical setting. We hypothesized MSE predicts death using HR data of shorter
      duration and lower density. During the initial 24 h of intensive care unit stay,
      3,154 patients had at least 3 h of continuous integer HR sampled. The first
      continuous window of 3, 6, 9, and 12 h was selected for each patient regardless
      of density, and an open-source MSE algorithm was applied (M. Costa,
      www.physionet.org; m = 2; r = 0.15). Risk of death based on MSE, alone and with
      covariates (age, sex, injury severity score), was assessed using randomly
      selected logistic regression in half of the cases. Area under the receiver
      operator curve (AUC) was computed in the other half in subgroups having various
      durations and densities of HR data. At days 2.3 (median) and 4.9 (mean), 441
      patients (14%) died. Multiscale entropy stratified patients by mortality and was
      an independent predictor of death using 3 h or more of data. Multiscale entropy
      alone (AUC = 0.66 - 0.71) predicted death comparably to covariates alone (AUC =
      0.72). We conclude: (1) Heart rate MSE within hours of admission predicts death
      occurring days later. (2) Multiscale entropy is robust to variation in bedside
      data duration and density occurring in a working intensive care unit. (3)
      Complexity may be a new clinical biomarker of outcome.

PMID- 18323738
TI  - Independent determinants of early death in critically ill surgical patients.
AB  - Abnormalities in cardiocirculatory, respiratory, or coagulatory parameters are
      frequent after major surgery, but so far, no study has investigated their
      predictive value for early intensive care unit (ICU) mortality. We aimed to
      describe and quantify the relation between these parameters that are routinely
      determined on ICU admission and early death after complex surgery. Individual
      patient data were available from a local ICU database. We performed a
      retrospective observational cohort study using prospectively collected data from
      March 1, 1993, through February 28, 2005. A cohort of 4,214 cases who were
      admitted to the ICU immediately after operation was analyzed. We studied age,
      sex, number of red blood cell units transfused on admission day, and admission
      values for heart rate, systolic blood pressure, hemoglobin concentration, partial
      thromboplastin time, prothrombin time, respiratory function (Pao2/Fio2 ratio),
      and body temperature for their association with 4-day mortality. Effects were
      adjusted for the underlying disease and for disease severity during the first 24
      h after admission. We used generalized additive models to fit continuous
      variables individually before combining them into the final generalized model. We
      found an independent linear association between the number of transfused red
      blood cell units, partial thromboplastin time, and body temperature with acute
      outcome. A smoothed model described the independent interaction between admission
      blood pressure and early death. Only values of less than 80 mmHg were associated
      with an increased risk of 4-day mortality. According to these results, bleeding
      complications after ICU admission should be treated aggressively to prevent early
      death of the patient. However, normotensive conditions do not seem to be required
      to prevent early mortality. Whether rapid rewarming may improve outcome needs
      further rigorous study.

PMID- 18323737
TI  - The role of endogenously produced extracellular hsp72 in mononuclear cell
      reprogramming.
AB  - Intracellular heat shock protein 72 (Hsp72) is known to serve a broad
      cytoprotective role. Recent data indicate that stressed cells can release Hsp72
      into the extracellular compartment, although the biological function of
      extracellular Hsp72 remains to be fully elucidated. Because extracellular Hsp72
      has been demonstrated to interact with Toll-like receptor 4, we hypothesized that
      endogenously produced and released Hsp72 would reprogram the mononuclear cell
      responses to LPS. THP-1 cells treated with LPS were used as a model for nuclear
      factor (NF)-kappaB activation. Heat shock conditions consisted of incubation at
      43 degrees C for 1 h. Control cells were incubated at 37 degrees C. Twenty four
      hours after incubation, heat shock conditioned media (HSCM) and control media
      (CM) were centrifuged, and the respective cells were discarded. A separate group
      of naive THP-1 cells were then incubated with either HSCM or CM for 18 h and then
      stimulated with LPS (1 mug/mL). Heat shock significantly increased Hsp72 in HSCM
      compared with CM. In THP-1 cells transfected with an NF-kappaB luciferase
      reporter plasmid, the addition of HSCM attenuated subsequent LPS-mediated
      luciferase activity compared with cells incubated in CM. The addition of HSCM
      also attenuated LPS-mediated NF-kappaB-DNA binding and IkappaBalpha degradation.
      Heat shock protein 72-mediated inhibition of NF-kappaB activation was further
      corroborated by a significant decrease in TNF-alpha production. When HSCM and CM
      were subjected to Hsp72 depletion via adenosine triphosphate-agarose binding, LPS
      mediated activation of NF-kappaB was partially restored, suggesting that Hsp72 is
      partially responsible for cellular reprogramming in response to HSCM. These data
      demonstrate that endogenously produced and released extracellular Hsp72 has the
      ability to reprogram the in vitro response to endotoxin in cultured human
      mononuclear cells.

PMID- 18323739
TI  - Ischemic postconditioning protects myocardium from ischemia/reperfusion injury
      through attenuating endoplasmic reticulum stress.
AB  - Ischemic postconditioning (I-postC) is a newly discovered endogenous protective
      phenomenon capable of protecting the myocardium from I/R injury. The
      cardioprotective mechanisms of I-postC involve protein synthesis and preventing
      an increase in cytosolic calcium. Endoplasmic reticulum (ER) is a principal site
      for secretory protein synthesis and calcium storage. Myocardial I/R causes ER
      stress and perturbations of ER function. The purpose of the present study was to
      determine whether I-postC's attenuation of I/R injury involves reductions in ER
      stress through mitogen-activated protein kinase (MAPK) pathway. In the present
      study, models of rat myocardial I/R and hypoxia/reoxygenation (H/R) of neonatal
      rat cardiomyocytes were used. Myocardial infarct size was measured by
      triphenyltetrazolium chloride staining, and flow cytometry was used to quantitate
      cardiomyocyte apoptosis. Calreticulin expression and activation of caspase 12,
      p38 MAPK, and c-Jun NH2-terminal kinase (JNK) in myocardium or cardiomyocytes
      were detected by Western blots. It is found that I-postC protects the I/R heart
      against myocardial infarction, and hypoxic postconditioning protects neonatal
      cardiomyocytes from H/R-induced apoptosis. Ischemic postconditioning suppressed
      I/R-induced ER stress, as shown by a decrease in calreticulin expression and
      caspase 12 activation. Hypoxic postconditioning up-regulates p38 MAPK
      phosphorylation and down-regulates JNK phosphorylation in cardiomyocytes
      subjected to H/R. These results indicate that I-postC protects myocardium from
      I/R injury by suppressing ER stress, and that p38 MAPK and JNK pathways are
      associated with the I-postC-induced suppression of ER stress.

PMID- 18323740
TI  - A 20-hydroxyeicosatetraenoic acid agonist, N-[20-hydroxyeicosa-5(Z),14(Z)
      dienoyl]glycine, opposes the fall in blood pressure and vascular reactivity in
      endotoxin-treated rats.
AB  - Endotoxic shock is a systemic inflammatory response that is associated with an
      increase in nitric oxide production and a decrease in the formation of 20
      hydroxyeicosatetraenoic acid (20-HETE), which may contribute to the fall in blood
      pressure and vascular reactivity. The present study examined the effects of a
      synthetic analogue of 20-HETE, N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine
      (5,14-HEDGE), on the fall in blood pressure and vascular responsiveness to
      vasoscontrictors and acetylcholine in rats treated with endotoxin. The MAP fell
      by 31 mmHg, and the heart rate rose by 90 beats/min in male Wistar rats treated
      with endotoxin (10 mg/kg, intraperitoneally). The fall in MAP was associated with
      a decrease in the vasoconstrictor response to norepinephrine in isolated aorta
      and superior mesenteric artery and increased levels of nitrite in the serum,
      kidney, heart, and vascular tissues. The effects of endotoxin were prevented by
      5,14-HEDGE (30 mg/kg, s.c.) given 1 h after injection of endotoxin. Furthermore,
      a competitive antagonist of vasoconstrictor effects of 20-HETE, 20-hydroxyeicosa
      6(Z),15(Z)-dienoic acid (30 mg/kg, s.c.), prevented the beneficial effects of
      5,14-HEDGE on MAP and vascular tone in rats treated with endotoxin. These data
      are consistent with the view that a fall in the production of 20-HETE contributes
      to the fall in MAP and vascular reactivity in rats treated with endotoxin, and
      that 5,14-HEDGE has a beneficial effect.

PMID- 18323741
TI  - Effect of esmolol on fluid therapy in normovolemia and hypovolemia.
AB  - beta-Adrenergic agonists can enhance vascular volume expansion after a fluid
      bolus. The present study addresses how the beta-adrenergic antagonist esmolol
      influences volume expansion and fluid balance during normovolemia (series 1) and
      hypovolemia (series 2). Sheep were instrumented, and the spleen was removed. For
      series 1, continuous infusion of 50 to 100 microg.kg(-1).min(-1) esmolol (n = 6)
      or control (no drug; n = 6) was begun 30 min before administration of a 24-mL kg(
      1) 20-min bolus of 0.9% NaCl. For series 2, anesthetized sheep were infused with
      50 to 100 microg.kg(-1).min(-1) esmolol (n = 6) or control (no drug; n = 6) 30
      min before a-20 mL kg(-1) hemorrhage. Fluid resuscitation (0.9% NaCl) was begun
      30 min after hemorrhage. The 24-mL kg(-1) 20-min bolus was followed by titrated
      fluid therapy. Hemoglobin, fluid in, and urinary output were used to calculate
      changes in plasma volume (DeltaPV), extravascular volume (DeltaEVV = fluid in -
      urinary output - DeltaPV), volume expansion efficiency (VEE = fluid in /
      DeltaPV), and fluid distribution ratio (DeltaPV/DeltaEVV). Hemodynamics for both
      series were similar with the exception of heart rate. In series 1, peak DeltaPV
      was 9.1 +/- 1.0 mL kg(-1) in control and 3.7 +/- 1.0 mL kg(-1) at study end.
      Esmolol resulted in a lower peak DeltaPV (6.4 +/- 2.0 mL kg(-1)) and a negative
      DeltaPV (-0.4 +/- 0.6 mL kg(-1)) at study's end. Urinary output was lower, and
      EVV was greater with esmolol. In series 2, esmolol increased fluid requirements
      (67 +/- 7 mL kg(-1)) compared with control (54 +/- 5 mL kg(-1)). Esmolol reduced
      DeltaPV/DeltaEVV. These data suggest that esmolol impairs the vascular retention
      of fluid and may increase the amount of volume support during fluid
      resuscitation.

PMID- 18323742
TI  - Hemodynamic and metabolic effects of hydrogen sulfide during porcine
      ischemia/reperfusion injury.
AB  - In awake spontaneously breathing mice, inhaling gaseous hydrogen sulfide (H2S)
      produced a "suspended animation-like" metabolic status with hypothermia and
      reduced O2 demand, thus protecting from lethal hypoxia. Murine models may be
      questioned, however, because due to their large surface area/mass ratio, rodents
      can rapidly drop their core temperature. Therefore, we investigated whether
      intravenous H2S (Na2S, sodium sulfide) would induce a comparable metabolic
      response in anesthetized and mechanically ventilated pigs. Because H2S was
      reported to improve heart function after myocardial ischemia, we also
      investigated whether sulfide would influence the noradrenaline responsiveness
      during reperfusion after aortic occlusion. After 2 h of i.v. sulfide (0.2 mg.kg
      followed by 2 mg.kg.per h; n=8) or vehicle (n=8), animals underwent 30 minutes of
      aortic occlusion with nitroglycerine, esmolol, and adenosine-5'-triphosphate
      adjusted to maintain MAP at 80% to 120% of baseline. During reperfusion,
      noradrenaline was titrated to keep MAP greater than or equal to 80% of this
      level. Sulfide reduced heart rate and cardiac output without affecting stroke
      volume, markedly decreased the time and dose of noradrenaline required to
      maintain hemodynamic targets, and caused a drop in core temperature concomitant
      with lower O2 uptake and CO2 production. Although arterial PCO2 and acid-base
      status were comparable, arterial PO2 was lower in the sulfide group at the end of
      the experiment. Sulfide attenuated the reperfusion-related hyperlactatemia,
      although glycemia was higher at the end of the experiment. The parameters of
      inflammation and oxidative stress did not differ. Intravenous sulfide allowed
      reducing energy expenditure in an anesthetized large-animal model and improved
      the noradrenaline responsiveness during reperfusion after aortic occlusion.
      Investigations are warranted, hence, whether it may also protect other organs
      after I/R injury.

PMID- 18323743
TI  - Surfactant dysfunction in lung contusion with and without superimposed gastric
      aspiration in a rat model.
AB  - This study investigates surfactant dysfunction in rats with lung contusion (LC)
      induced by blunt chest trauma. Rats at 24 h postcontusion had a decreased percent
      content of large surfactant aggregates in cell-free bronchoalveolar lavage (BAL)
      and altered large-aggregate composition with decreased phosphatidylcholine (PC),
      increased lyso-PC, and increased protein compared with uninjured controls. The
      surface activity of large aggregates on a pulsating bubble surfactometer was also
      severely impaired at 24 h postcontusion. Decreases in large surfactant aggregate
      content and surface activity were improved, but still apparent, at 48 and 72 h
      postcontusion compared with uninjured control rats and returned to normal by 96 h
      postcontusion. The functional importance of surfactant abnormalities in LC injury
      was documented in pilot studies showing that exogenous surfactant replacement at
      24 h postcontusion improved inflation/deflation lung volumes. Additional
      experiments investigated a clinically relevant combination of LC plus gastric
      aspiration (combined acid and small gastric food particles) and found reductions
      in large surfactant aggregates in BAL similar to those for LC. However, rats
      given LC + combined acid and small gastric food particles versus LC had more
      severe surfactant dysfunction based on decreases in surface activity and
      alterations in large aggregate composition. Combined data for all animal groups
      had strong statistical correlations between surfactant dysfunction (increased
      minimum surface tension, decreased large aggregates in BAL, decreased aggregate
      PC, and increased aggregate lyso-PC) and the severity of inflammatory lung injury
      (increased total protein, albumin, protein/phospholipid ratio, neutrophils, and
      erythrocytes in BAL plus increased whole lung myeloperoxidase activity). These
      results show that surfactant dysfunction is important in the pathophysiology of
      LC with or without concurrent gastric aspiration and provides a rationale for
      surfactant replacement therapy in these prevalent clinical conditions.

PMID- 18323745
TI  - Altered gene expression patterns in dendritic cells after severe trauma:
      implications for systemic inflammation and organ injury.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells and members of
      the adoptive immunity. In addition, they play an important role in innate
      immunity within the systemic inflammatory response to trauma and sepsis. In this
      study, gene expression patterns of DC in patients with multiple trauma were
      studied. Total RNA was isolated from highly purified DCs (purity>95%) that were
      enriched from peripheral blood mononuclear cells and whole blood, respectively.
      Samples were obtained from 10 multiple trauma patients (injury severity score,
      35.4+/-10.6 on day of admission) and 5 healthy volunteers (control). Aliquots of
      target cDNAs and reference samples (cDNA derived from the monocytic cell line
      SIGM5) were cohybridized on a thematic medium-density microarray assessing 780
      inflammation-related transcripts. Twenty transcripts were up-regulated in DCs of
      multiple trauma patients compared with healthy volunteers, whereas these
      differences were missed when RNA from whole blood was subjected to transcriptomic
      profiling. This cluster included central effector molecules of DC such as
      transcripts encoding for 5-lipoxygenase and the corresponding leukotriene 4
      receptor, which regulate DC migration, adoptive immune responses, and airway
      inflammation, as well as CD74, CXCL4, or platelet factor 4, a chemokine not
      implicated as a product of DCs to date. In addition, genes involved in
      antiapoptosis (BCL2), intracellular signal transduction (mitogen-activated
      protein kinase), and secretion of mediators (VAMP2) were found to be up
      regulated. The up-regulated transcripts suggest that life span and signaling
      function of DCs are altered by trauma. Furthermore, these data confirm and expand
      the central role of chemokines and lipid mediators as effector molecules of DC
      mediated immune responses in systemic inflammation associated with severe trauma.

PMID- 18323746
TI  - Role of neutrophil elastase in development of pulmonary vascular injury and
      septic shock in rats.
AB  - Prostacyclin prevents pulmonary vascular injury and shock by inhibiting increases
      in lung tissue levels of TNF in rats administered endotoxin. We previously
      reported that NO derived from eNOS increases endothelial production of
      prostacyclin. Because neutrophil elastase has been shown to decrease endothelial
      production of prostacyclin by inhibiting NOS activity, we examined whether
      neutrophil elastase inhibitors reduce pulmonary vascular injury and hypotension
      by inhibiting the decrease in pulmonary endothelial production of prostacyclin in
      rats administered endotoxin. Animals were pretreated with sivelestat or L
      658,758, neutrophil elastase inhibitors, before endotoxin administration. Lung
      tissue levels of 6-keto-prostaglandin F1alpha were markedly increased after
      endotoxin administration, followed by a rapid decrease to baseline levels.
      Sivelestat and L-658,758 inhibited these decreases as well as inhibiting
      increases in lung tissue levels of TNF and lung wet-to-dry weight ratios in
      animals administered endotoxin. These inhibitors also reduced hypotension and
      inhibited increases in lung tissue levels of mRNA of the inducible form of NOS in
      animals administered endotoxin. The effects of neutrophil elastase inhibitors
      were completely reversed by pretreatment with nitro-L-arginine methyl ester, an
      inhibitor of NOS, or indomethacin, a nonspecific cyclooxygenase inhibitor. These
      observations suggested that neutrophil elastase might decrease the pulmonary
      endothelial production of prostacyclin by inhibiting endothelial NO production,
      thereby contributing to the development of pulmonary vascular injury and shock
      through increases in lung tissue levels of TNF in rats administered endotoxin.

PMID- 18323747
TI  - Burn plasma transfer induces burn edema in healthy rats.
AB  - Thermal injuries greater than 20% body surface area (BSA) result in systemic
      shock with generalized edema in addition to local tissue destruction. Burn shock
      is induced by a variety of mediators, mainly immunomodulative cytokines. This
      experimental study evaluates if burn shock can be induced in healthy rats by
      transfer of burn plasma (BP) with mediators. Thermal injury was induced by hot
      water (100 degrees C water, 12 s, 30% BSA) in male syngenic Wistar rats. Donor
      rats were killed 4 h posttrauma, and BP was harvested. Burn plasma was
      transferred to healthy animals by continuous intravenous infusion in three types
      of dilution (100%, 10%, and 1%). Positive controls were directly examined 4 h
      after thermal injury, and negative control rats had a continuous infusion done
      with sham burn (SB) plasma (37 degrees C water, 12 s, 30% BSA). Afterwards,
      intravital fluorescence microscopy was performed in postcapillary mesenteric
      venules at 0, 60, and 120 min. Edema formation was assessed by relative changes
      over time in fluorescence intensity of fluorescein isothiocyanate-albumin in the
      intravascular versus the extravascular space. The interactions of leucocytes and
      endothelium were evaluated by quantification of leukocyte sticking. Additionally,
      microhemodynamic (volumetric blood flow, erythrocyte velocity, venular wall shear
      rate, venular diameters) and macrohemodynamic parameters (blood pressure, heart
      frequency, temperature) were assessed online (arterial catheter). For statistics,
      an ANOVA was performed with Bonferroni adjustment procedure. Differences were
      considered significant when P < 0.05. There are no statistically significant
      differences in microhemodynamics or macrohemodynamics between study groups. Burn
      plasma infusion and thermal injury lead to significant increases in fluorescein
      isothiocyanate-albumin extravasation, whereas SB plasma shows no significant
      changes. Even BP diluted in 0.9% saline (10% and 1%) results in a similar
      transvascular flux of plasma proteins as direct thermal injury. Differences
      between positive controls and BP infusion are not significant, whereas all groups
      are statistically different from the SB group (P<0.05). Leukocyte sticking is
      significantly increased in all groups except the SB group, and the number of
      adherent leukocytes is dose dependent. The present study demonstrates that as
      early as 4 h after thermal injury, there are sufficient factors (e.g., cytokines)
      in BP to induce systemic burn shock in healthy rats even in diluted plasma (1%).
      However, the "key" cytokines are not identified at this point. The burned tissue
      is no longer required for burn shock induction, and the pathophysiologic process
      seems to be self-perpetuating as early as 4 h posttrauma. Leukocytes are
      activated by thermal injury and BP infusion. The role of leukocyte-endothelium
      interactions for edema formation remains uncertain and requires further
      investigation.

PMID- 18323748
TI  - Mortality predictions using current physiologic scoring systems in patients
      meeting criteria for early goal-directed therapy and the severe sepsis
      resuscitation bundle.
AB  - Physiologic scoring systems are often used to prognosticate mortality in
      critically ill patients. This study examined the performance of Acute Physiology
      and Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score
      (SAPS) II, Mortality in Emergency Department Sepsis (MEDS), and Mortality
      Probability Models (MPM) II0 in predicting in-hospital mortality of patients in
      the emergency department meeting criteria for early goal-directed therapy and the
      severe sepsis resuscitation bundle. The discrimination and calibration
      characteristics of APACHE II, SAPS II, MEDS, and MPM II0 were evaluated. Data are
      presented as median and quartiles (25th, 75th). Two-hundred forty-six patients
      aged 68 (52, 81) years were analyzed from a prospectively maintained sepsis
      registry, with 76.0% of patients in septic shock, 45.5% blood culture positive,
      and 35.0% in-hospital mortality. Acute Physiology and Chronic Health Evaluation
      II, SAPS II, and MEDS scores were 29 (21, 37), 54 (40, 70), and 13 (11, 16), with
      predicted mortalities of 64% (40%, 85%), 58% (25%, 84%), and 16% (9%, 39%),
      respectively. Mortality Probability Models II0 showed a predicted mortality of
      60% (27%, 80%). The area under the receiver operating characteristic curves was
      0.73 for APACHE II, 0.71 for SAPS II, 0.60 for MEDS, and 0.72 for MPM II0. The
      standardized mortality ratios were 0.59, 0.63, 1.68, and 0.64, respectively.
      Thus, APACHE II, SAPS II, MEDS, and MPM II0 have variable abilities to
      discriminate early and estimate in-hospital mortality of patients presenting to
      the emergency department requiring the severe sepsis resuscitation bundle.
      Adoption of these prognostication tools in this setting may influence therapy and
      resource use for these patients.

PMID- 18323749
TI  - Increased aerobic glycolysis through beta2 stimulation is a common mechanism
      involved in lactate formation during shock states.
AB  - During septic shock, muscle produces lactate by way of an exaggerated NaK
      adenosine triphosphatase (ATPase)-stimulated aerobic glycolysis associated with
      epinephrine stimulation possibly through beta2 adrenoreceptor involvement. It
      therefore seems logical that a proportion of hyperlactatemia in low cardiac
      output states would be also related to this mechanism. Thus, in low-flow and
      normal-to-high-flow models of shock, we investigate (1) whether muscle produces
      lactate and (2) whether muscle lactate production is linked to beta2 adrenergic
      stimulation and Na+K+-ATPase. We locally modulated the adrenergic pathway and
      Na+K+-ATPase activity in male Wistar rats' skeletal muscle using microdialysis
      with nonselective and selective beta blockers and ouabain in different models of
      rodent shock (endotoxin, peritonitis, and hemorrhage). Blood flow at the probe
      site was evaluated by ethanol clearance. We measured the difference between
      muscle lactate and blood lactate concentration, with a positive gradient
      indicating muscle lactate or pyruvate production. Epinephrine levels were
      elevated in all shock groups. All models were associated with hypotension and
      marked hyperlactatemia. Muscle lactate concentrations were consistently higher
      than arterial levels, with a mean gradient of 2.5+/-0.3 in endotoxic shock, 2.1+/
      0.2 mM in peritonitis group, and 0.9+/-0.2 mM in hemorrhagic shock (P<0.05 for
      all groups). Muscle pyruvate concentrations were also always higher than arterial
      levels, with a mean gradient of 260+/-40 microM in endotoxic shock, 210+/-30
      microM in peritonitis group, and 90+/-10 microM in hemorrhagic shock (P<0.05 for
      all groups). Despite a decrease in blood flow, lactate formation was decreased by
      all the pharmacological agents studied irrespective of shock mechanism. This
      demonstrates that lactate production during shock states is related, at least in
      part, to increased NaK-ATPase activity under beta2 stimulation. In shock state
      associated with a reduced or maintained blood flow, an important proportion of
      muscle lactate release is regulated by a beta2 receptor stimulation and not
      secondary to a reduced oxygen availability.

PMID- 18323750
TI  - "Functional" and "organic": it is getting harder to tell the difference.

PMID- 18323751
TI  - rTMS in headache prophylaxis: when case reports hide our ignorance.

PMID- 18323752
TI  - Emotional regulation: implications for the psychobiology of psychotherapy.
AB  - A range of studies have contributed to understanding the psychobiology of
      emotional regulation. Functional imaging studies have demonstrated that cortico
      limbic circuitry plays an important role in mediating processes such as
      reappraisal and suppression. Dorsolateral prefrontal cortex may be important in
      conscious reframing, while ventromedial prefrontal cortex and orbitofrontal
      cortex may be particularly important in emotion evaluation. Gene variants and
      early environments impact underlying emotional regulation and its neurobiology.
      It may be hypothesized that during interventions such as psychotherapy there are
      improvements in emotional regulation, together with the normalization of related
      psychobiological mechanisms.

PMID- 18323753
TI  - The spectrum of recurrent thoughts and behaviors in frontotemporal dementia.
AB  - This article describes the spectrum of recurrent thoughts and behaviors that can
      result from frontotemporal dementia (FTD) and its variants. Although repetitive
      behaviors can result from a range of brain disorders, FTD is the most common
      neurologic cause of new-onset recurrent thoughts and behaviors in middle or late
      life. Patients with FTD can manifest typical or bizarre compulsions, hoarding,
      verbal and motor stereotypies and complex tics; self-injurious acts,
      perseverations; and fixed, obsessional thoughts. The frequency and variability of
      these repetitive behaviors suggest a common disturbance of orbitofrontal-basal
      ganglia circuits involved in response inhibition. The amelioration of these
      recurrent events with the administration of serotonin selective reuptake
      inhibitors further suggests a serotonergic deficit.

PMID- 18323754
TI  - Delirium and isolated angiitis of the central nervous system: a case report and
      review.
AB  - Central nervous system (CNS) vasculitis is a rare entity, especially when it
      occurs in isolation; it is seen more commonly as part of a multisystem
      vasculitis. Common presenting symptoms include persistent headache,
      encephalopathy, and multifocal signs. We discuss the case of a 68-year-old female
      who presented twice in 1 month with confusion and choreaform movements. Extensive
      workup was negative for a connective tissue disease or other conditions in the
      differential, including neurosarcoidosis, Creutzfeldt-Jakob disease, and
      neurosyphilis. The only significant findings were elevated erythrocyte
      sedimentation rate, inflammatory signs in the CNS, and diffuse slowing of the
      electroencephalogram. A presumptive diagnosis of isolated angiitis of the central
      nervous system (IACNS) was made and the patient was successfully treated with
      steroids. She recovered fully with no residual symptoms. The diagnosis of IACNS
      is often difficult given there are no definitive laboratory investigations or
      pathognomonic presentation. However, a series of signs, symptoms, and laboratory
      findings have been proposed that are helpful in making the diagnosis. To our
      knowledge, IACNS presenting primarily with delirium has not been previously
      reported in the literature. The diagnosis of IACNS is purely speculative for this
      case, as the gold standard for diagnosis, a leptomeningeal cortical biopsy, was
      not performed.

PMID- 18323755
TI  - Characteristics and symptomatology of patients diagnosed with unipolar depression
      at risk for undiagnosed bipolar disorder: a bipolar survey.
AB  - OBJECTIVE: To identify characteristics of patients diagnosed with unipolar
      depression who may have undiagnosed bipolar disorder. METHODS: Patients diagnosed
      with unipolar depression by a healthcare provider were identified through the
      Consumer Health Sciences National Health and Wellness Survey. Manic symptoms,
      comorbid conditions, psychiatric symptomatology, use of healthcare resources, and
      patient demographics were identified through Internet-based questionnaires. A
      self-report adapted version of Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition-Text Revision criteria identified symptoms consistent
      with a manic episode. Psychological well-being was measured by the Psychological
      General Well-Being Index. RESULTS: Of the 1,602 respondents who met inclusion
      criteria, 219 (14% or approximately 1 out of 7) reported symptoms consistent with
      a manic episode and were considered at risk for undiagnosed bipolar disorder.
      These respondents were younger and had a lower socioeconomic status. At-risk
      patients rated their depression as more severe and experienced greater impairment
      of psychological well-being. More than 70% of those at risk reported speaking
      with a healthcare provider about their mania symptoms. Comorbid mental disorders,
      especially anxiety-related conditions, were common in these patients. CONCLUSION:
      These findings underscore the importance of evaluating unipolar patients for
      bipolar disorder and may help clinicians identify symptoms and comorbidities
      associated with patients with unipolar depression at risk for undiagnosed bipolar
      disorder.

PMID- 18323756
TI  - Cooling core body temperature may slow down neurodegeneration.
AB  - Reduction of core body temperature has been proposed to contribute to the
      increased lifespan and the anti-aging effects conferred by caloric restriction in
      mice and higher primates. Cooler biologically compatible core body temperatures
      have also been hypothesized to combat neurodegenerative disorders. Yet,
      validation of these hypotheses has been difficult until recently, when it
      demonstrated that transgenic mice engineered to have chronic low core body
      temperature have longer lifespan independent of alteration in diet or caloric
      restriction. This article reviews the literature and highlights the potential
      influence of core body temperature's governing role on aging and in the
      pathophysiology of neurodegenerative disorders in humans. What makes recent
      findings more significant for humans is the existence of several methods to lower
      and maintain low core body temperatures in human subjects. The therapeutic
      potential of "cooler people" may also raise the possibility that this could
      reverse the adverse-health consequences of elevations in core body temperature.

PMID- 18323757
TI  - Comorbid HIV encephalopathy and cocaine use as a risk factor for new-onset
      seizure disorders.
AB  - Patients living with human immunodeficiency virus represent a growing population,
      and an increased number of central nervous system presentations can be expected
      over the next decade. Emerging data suggests that both HIV-seropositive patients
      and cocaine-abusing patients may be at special risk of seizure phenomena. This
      case report discusses the risks of new-onset seizure activity when these two risk
      factors converge, which is a common occurrence in this population. Data from the
      fields of neuroanatomy and neurovirology are presented to explain the heightened
      risk of this patient population and provide the practitioner with an improved
      understanding of the central nervous system complexities in HIV.

PMID- 18323759
TI  - Introduction: the prevalence of Alzheimer's disease--a growing crisis.

PMID- 18323758
TI  - Gender-related differences in individuals seeking treatment for kleptomania.
AB  - OBJECTIVE: Understanding variations in disease presentation in men and women is
      clinically important as differences may reflect biological and sociocultural
      factors and have implications for prevention and treatment strategies. Few
      empirical investigations have been performed in kleptomania, particularly with
      respect to gender-related influences. METHODS: From 2001--2007, 95 adult subjects
      (n=27 [28.4%] males) with Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition-defined kleptomania were assessed on sociodemographics and
      clinical characteristics, including symptom severity, comorbidity, and functional
      impairment, to identify gender-related differences. RESULTS: Men and women showed
      substantial symptom severity and functional impairment. Compared with affected
      men, women with kleptomania were more likely to be married (47.1% vs 25.9%;
      P=.039), have a later age at shoplifting onset (20.9 vs 14 years of age; P=.001),
      steal household items (P<.001), hoard stolen items (P=.020), and have an eating
      disorder (P=.017) and less likely to steal electronic goods (P<.001) and have
      another impulse-control disorder (P=.018). CONCLUSION: Kleptomania is similarly
      associated with significant impairment in women and men. Gender-related
      differences in clinical features and co-occurring disorders suggest that
      prevention and treatment strategies incorporate gender considerations.

PMID- 18323760
TI  - Taking a closer look at sleep problems and psychosis in Parkinson's disease.
      Introduction.

PMID- 18323761
TI  - Sleep disorders associated with Parkinson's disease: role of dopamine,
      epidemiology, and clinical scales of assessment.
AB  - Sleep dysfunction is common among patients with Parkinson's disease and occurs in
      approximately two thirds of patients. The problems range from nocturnal issues
      such as difficulty with sleep initiation, sleep fragmentation, disturbance of
      circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime
      problems such as excessive daytime sleepiness. Frequent nighttime awakening and
      sleep disruption are the most common sleep problems in Parkinson's disease.
      Dopamine plays an important role in maintaining wakefulness. To improve sleep in
      Parkinson's disease, it is important to achieve the critical balance of adequate
      dopaminergic therapy and control of symptoms. Increased dopaminergic agents can
      cause dyskinesias and painful dystonia, and undertreatment can cause nighttime
      akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs
      commonly used in Parkinson's disease can also affect sleep. In patients with
      advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus
      has a favorable impact on sleep quality and sleep architecture.

PMID- 18323762
TI  - Sleep disturbances and Parkinson's disease.
AB  - Although Parkinson's disease is defined by its motor symptoms, the symptoms that
      are most devastating to patients and caregivers are dementia and psychosis. In
      addition, sleep has a tremendous impact on patient well being and quality of
      life. Eighty percent to 90% of Parkinson's disease patients have a sleep disorder
      affecting their ability to fall asleep, ability to stay asleep, dreams, motor
      activity during sleep, post-sleep behavior, or daytime somnolence. Treatment
      plans for patients with Parkinson's disease who experience sleep disorders aim to
      improve nighttime sleep or daytime wakefulness, and treatment options vary by
      sleep disorder.

PMID- 18323763
TI  - Psychosis in Parkinson's disease: phenomenology, frequency, risk factors, and
      current understanding of pathophysiologic mechanisms.
AB  - Psychosis in Parkinson's disease refers to a combination of hallucinations and
      delusions occurring with a clear sensorium and a chronic course. Hallucinations
      may involve several sensory modalities. Complex visual hallucinations are the
      most common type. "Minor" hallucinatory phenomena are frequently present and
      include visual illusions, passage hallucinations, and sense of presence. Insight
      may be lost in patients with cognitive impairment. Delusions of a paranoid type
      are more rare than hallucinations. Both hallucinations and delusions are more
      frequent in Parkinson's disease patients with dementia. Pathogenesis involves
      complex and probably multifactorial mechanisms, including pharmacologic
      (dopaminergic treatment and others) and disease-related factors.

PMID- 18323764
TI  - Course, prognosis, and management of psychosis in Parkinson's disease: are
      current treatments really effective?
AB  - It is essential to recognize and treat psychosis in Parkinson's disease for
      several reasons. Studies have shown that psychosis in Parkinson's disease
      patients is a strong risk factor for nursing home placement. Psychosis may be the
      greatest source of stress for caretakers of Parkinson's patients; it is often
      persistent, and its presence markedly increases mortality. Treatment of psychotic
      symptoms should occur only after potential medical and environmental causes of
      delirium have been eliminated or addressed. Initial pharmacologic changes should
      include limiting the patient's antiparkinsonian medications to those that are
      necessary to preserve motor function. Should that fail, an atypical antipsychotic
      is presently the treatment of choice. An emerging treatment option is
      acetylcholinesterase inhibitors. This article reviews what is currently known
      about the course, prognosis, and treatment strategies in Parkinson's disease
      psychosis.

PMID- 18323765
TI  - What we have learned about sleep disorders and psychosis after nearly two
      centuries of Parkinson's disease. Summary and conclusions.

PMID- 18323766
TI  - Fibromyalgia syndrome: new developments in pathophysiology and management.
      Introduction.

PMID- 18323767
TI  - Fibromyalgia syndrome: presentation, diagnosis, differential diagnosis, and
      vulnerability.
AB  - Fibromyalgia syndrome (FMS) presents with widespread soft tissue pain. Common
      comorbidities include severe insomnia, body stiffness, affective symptoms,
      irritable bowels, and urethral syndrome. A 1990 research classification depends
      on a history of widespread pain and prominent tenderness to palpation at 11 or
      more of 18 specific tender points. It is a criteria-based diagnosis rather than
      one by exclusion and can accompany other medical conditions. FMS occurs
      worldwide, and can present any age, but is most common in adult females. Although
      numerous studies and reviews contend that FMS may be caused by psychological
      stress such as sexual abuse, critical epidemiological review fails to support
      that concept. Existing data suggest that some individuals with FMS may have a
      dysregulated physiological stress response system that predates the onset of
      symptoms.

PMID- 18323768
TI  - Psychophysical and neurochemical abnormalities of pain processing in
      fibromyalgia.
AB  - Fibromyalgia pain is frequent in the general population, but its pathogenesis is
      only partially understood. Patients with fibromyalgia lack consistent tissue
      abnormalities but display features of hyperalgesia (increased sensitivity to
      painful stimuli) and allodynia (lowered pain threshold). Many recent fibromyalgia
      studies have demonstrated central nervous system (CNS) pain processing
      abnormalities, including abnormal temporal summation of pain. In the CNS,
      persistent nociceptive input from peripheral tissues can lead to neuroplastic
      changes resulting in central sensitization and pain. This mechanism appears to
      represent a hallmark of fibromyalgia and many other chronic pain syndromes,
      including irritable bowel syndrome, temporomandibular disorder, migraine, and low
      back pain. Importantly, after central sensitization has been established, only
      minimal peripheral input is required for the maintenance of the chronic pain
      state. Additional factors, including pain-related negative affect and poor sleep
      have been shown to significantly contribute to clinical fibromyalgia pain. Better
      understanding of these mechanisms and their relationship to central sensitization
      and clinical pain will provide new approaches for the prevention and treatment of
      fibromyalgia and other chronic pain syndromes.

PMID- 18323769
TI  - Social influences on the concept of fibromyalgia.
AB  - Despite relevant evidence of physical illness promoting fibromyalgia syndrome
      (FMS), some authors claim that it is a psychological illness, or due to
      "psychological amplification." Good evidence for such views is lacking. Selection
      processes lead to increased rates of psychological illness in general practice
      and in specialist practice. The physical distress of FMS can increase both
      anxiety and depression. Questionable research supported by the insurance industry
      has tended to provide negative and disparaging views of pain. Current imaging
      studies support the view that central effects connected with FMS relate to the
      processing of noxious stimulation more than affective disorder.

PMID- 18323770
TI  - The significance, assessment, and management of nonrestorative sleep in
      fibromyalgia syndrome.
AB  - People with fibromyalgia syndrome (FMS) experience unrefreshing sleep, aches,
      hypersensitivity, and cognitive and emotional difficulties. Although no specific
      causative factor or biological agent is known to account for all of the features
      of FMS and these related diagnoses, the generalized hypersensitivity of the body
      is considered to be affected by disturbances in central nervous system (CNS)
      functions. Such CNS disturbances are intrinsic to the sleeping-waking brain,
      where the common symptom elements in all these illnesses are poor quality of
      sleep, nonspecific pain, fatigue, and psychological distress in the absence of
      known disease pathology.

PMID- 18323771
TI  - Fibromyalgia syndrome: approach to management.
AB  - The management of fibromyalgia syndrome (FMS) has traditionally been multimodal
      and multidisciplinary, including education, physical modalities, and medication.
      In this article, an acronym is offered to help the clinician remember the
      important components of management. An improved understanding of the pathogenesis
      of FMS has allowed substantial refinements in its treatment. This is particularly
      true for medications that target specific symptom domains, allowing
      individualization of therapy. Since all FMS patients experience pain, there has
      been emphasis on that domain although medications are now available to address
      two or more domains with monotherapy. In addition, a logical basis is provided to
      help the clinician design strategic polypharmacy..

PMID- 18323772
TI  - Nebivolol (Bystolic) for hypertension.

PMID- 18323773
TI  - Gluten-free drugs for celiac disease patients.

PMID- 18323774
TI  - Heat shock response relieves ER stress.
AB  - Accumulation of misfolded protein in the endoplasmic reticulum (ER) causes
      stress. The unfolded protein response (UPR), a transcriptional induction pathway,
      is activated to relieve ER stress. Although UPR is not essential for viability,
      UPR-deficient cells are more sensitive to ER stress; ire1Delta cells cannot grow
      when challenged with tunicamycin or by overexpression of misfolded CPY(*). In
      these cells, multiple functions are defective, including translocation, ER
      associated degradation (ERAD), and ER-to-Golgi transport. We tested whether heat
      shock response (HSR) can relieve ER stress. Using a constitutively active Hsf1
      transcription factor to induce HSR without temperature shift, we find that HSR
      rescues growth of stressed ire1Delta cells, and partially relieves defects in
      translocation and ERAD. Cargo-specific effects of constitutively active Hsf1 on
      ER-to-Golgi transport are correlated with enhanced protein levels of the
      respective cargo receptors. In vivo, HSR is activated by ER stress, albeit to a
      lower level than that caused by heat. Genomic analysis of HSR targets reveals
      that >25% have function in common with UPR targets. We propose that HSR can
      relieve stress in UPR-deficient cells by affecting multiple ER activities.

PMID- 18323775
TI  - ZFPL1, a novel ring finger protein required for cis-Golgi integrity and efficient
      ER-to-Golgi transport.
AB  - The Golgi apparatus occupies a central position within the secretory pathway, but
      the molecular mechanisms responsible for its assembly and organization remain
      poorly understood. We report here the identification of zinc finger protein-like
      1 (ZFPL1) as a novel structural component of the Golgi apparatus. ZFPL1 is a
      conserved and widely expressed integral membrane protein with two predicted zinc
      fingers at the N-terminus, the second of which is a likely ring domain. ZFPL1
      directly interacts with the cis-Golgi matrix protein GM130. Depletion of ZFPL1
      results in the accumulation of cis-Golgi matrix proteins in the intermediate
      compartment (IC) and the tubulation of cis-Golgi and IC membranes. Loss of ZFPL1
      function also impairs cis-Golgi assembly following brefeldin A washout and slows
      the rate of cargo trafficking into the Golgi apparatus. Effects upon Golgi matrix
      protein localization and cis-Golgi structure can be rescued by wild-type ZFPL1
      but not mutants defective in GM130 binding. Together, these data suggest that
      ZFPL1 has an important function in maintaining the integrity of the cis-Golgi and
      that it does so through interactions with GM130.

PMID- 18323776
TI  - Subversion of CtBP1-controlled macropinocytosis by human adenovirus serotype 3.
AB  - Endocytosis supports cell communication, growth, and pathogen infection. The
      species B human adenovirus serotype 3 (Ad3) is associated with epidemic
      conjunctivitis, and fatal respiratory and systemic disease. Here we show that Ad3
      uses dynamin-independent endocytosis for rapid infectious entry into epithelial
      and haematopoietic cells. Unlike Ad5, which uses dynamin-dependent endocytosis,
      Ad3 endocytosis spatially and temporally coincided with enhanced fluid-phase
      uptake. It was sensitive to macropinocytosis inhibitors targeting F-actin,
      protein kinase C, the sodium-proton exchanger, and Rac1 but not Cdc42. Infectious
      Ad3 macropinocytosis required viral activation of p21-activated kinase 1 (PAK1)
      and the C-terminal binding protein 1 of E1A (CtBP1), recruited to macropinosomes.
      These macropinosomes also contained the Ad3 receptors CD46 and alpha v integrins.
      CtBP1 is a phosphorylation target of PAK1, and is bifunctionally involved in
      membrane traffic and transcriptional repression of cell cycle, cancer, and innate
      immunity pathways. Phosphorylation-defective S147A-CtBP1 blocked Ad3 but not Ad5
      infection, providing a direct link between PAK1 and CtBP1. The data show that
      viruses induce macropinocytosis for infectious entry, a pathway used in antigen
      presentation and cell migration.

PMID- 18323777
TI  - Spatial separation of Golgi and ER during mitosis protects SREBP from unregulated
      activation.
AB  - Sterol regulatory element-binding proteins (SREBPs) are membrane-bound
      transcription factors that reside as inactive precursors in the endoplasmic
      reticulum (ER) membrane. After sterol depletion, the proteins are transported to
      the Golgi apparatus, where they are cleaved by site-1 protease (S1P). Cleavage
      releases the active transcription factors, which then enter the nucleus to induce
      genes that regulate cellular levels of cholesterol and phospholipids. This
      regulation depends on the spatial separation of the Golgi and the ER, as mixing
      of the compartments induces unregulated activation of SREBPs. Here, we show that
      S1P is localized to the Golgi, but cycles continuously through the ER and becomes
      trapped when ER exit is inhibited. During mitosis, S1P is associated with mitotic
      Golgi clusters, which remain distinct from the ER. In mitotic cells, S1P is
      active, but SREBP is not cleaved as S1P and SREBP reside in different
      compartments. Together, these results indicate that the spatial separation of the
      Golgi and the ER is maintained during mitosis, which is essential to protect the
      S1P substrate SREBP from unregulated activation during mitosis.

PMID- 18323778
TI  - Dimer ribbons of ATP synthase shape the inner mitochondrial membrane.
AB  - ATP synthase converts the electrochemical potential at the inner mitochondrial
      membrane into chemical energy, producing the ATP that powers the cell. Using
      electron cryo-tomography we show that the ATP synthase of mammalian mitochondria
      is arranged in long approximately 1-microm rows of dimeric supercomplexes,
      located at the apex of cristae membranes. The dimer ribbons enforce a strong
      local curvature on the membrane with a 17-nm outer radius. Calculations of the
      electrostatic field strength indicate a significant increase in charge density,
      and thus in the local pH gradient of approximately 0.5 units in regions of high
      membrane curvature. We conclude that the mitochondrial cristae act as proton
      traps, and that the proton sink of the ATP synthase at the apex of the
      compartment favours effective ATP synthesis under proton-limited conditions. We
      propose that the mitochondrial ATP synthase organises itself into dimer ribbons
      to optimise its own performance.

PMID- 18323779
TI  - Proteolysis of AKAP121 regulates mitochondrial activity during cellular hypoxia
      and brain ischaemia.
AB  - A-kinase anchor protein 121 (AKAP121) assembles a multivalent signalling complex
      on the outer mitochondrial membrane that controls persistence and amplitude of
      cAMP and src signalling to mitochondria, and plays an essential role in oxidative
      metabolism and cell survival. Here, we show that AKAP121 levels are regulated
      post-translationally by the ubiquitin/proteasome pathway. Seven In-Absentia
      Homolog 2 (Siah2), an E3-ubiquitin ligase whose expression is induced in hypoxic
      conditions, formed a complex and degraded AKAP121. In addition, we show that
      overexpression of Siah2 or oxygen and glucose deprivation (OGD) promotes Siah2
      mediated ubiquitination and proteolysis of AKAP121. Upregulation of Siah2, by
      modulation of the cellular levels of AKAP121, significantly affects mitochondrial
      activity assessed as mitochondrial membrane potential and oxidative capacity.
      Also during cerebral ischaemia, AKAP121 is degraded in a Siah2-dependent manner.
      These findings reveal a novel mechanism of attenuation of cAMP/PKA signaling,
      which occurs at the distal sites of signal generation mediated by proteolysis of
      an AKAP scaffold protein. By regulating the stability of AKAP121-signalling
      complex at mitochondria, cells efficiently and rapidly adapt oxidative metabolism
      to fluctuations in oxygen availability.

PMID- 18323780
TI  - Regulation of nif gene expression and the energetics of N2 fixation over the diel
      cycle in a hot spring microbial mat.
AB  - Nitrogen fixation, a prokaryotic, O2-inhibited process that reduces N2 gas to
      biomass, is of paramount importance in biogeochemical cycling of nitrogen. We
      analyzed the levels of nif transcripts of Synechococcus ecotypes, NifH subunit
      and nitrogenase activity over the diel cycle in the microbial mat of an alkaline
      hot spring in Yellowstone National Park. The results showed a rise in nif
      transcripts in the evening, with a subsequent decline over the course of the
      night. In contrast, immunological data demonstrated that the level of the NifH
      polypeptide remained stable during the night, and only declined when the mat
      became oxic in the morning. Nitrogenase activity was low throughout the night;
      however, it exhibited two peaks, a small one in the evening and a large one in
      the early morning, when light began to stimulate cyanobacterial photosynthetic
      activity, but O2 consumption by respiration still exceeded the rate of O2
      evolution. Once the irradiance increased to the point at which the mat became
      oxic, the nitrogenase activity was strongly inhibited. Transcripts for proteins
      associated with energy-producing metabolisms in the cell also followed diel
      patterns, with fermentation-related transcripts accumulating at night,
      photosynthesis- and respiration-related transcripts accumulating during the day
      and late afternoon, respectively. These results are discussed with respect to the
      energetics and regulation of N2 fixation in hot spring mats and factors that can
      markedly influence the extent of N2 fixation over the diel cycle.

PMID- 18323781
TI  - Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell
      death, and abrogates invasive growth of melanoma cells.
AB  - The RAS-RAF-MEK-ERK and PI3K-AKT-mTOR signaling pathways are activated through
      multiple mechanisms and appear to play a major role in melanoma progression.
      Herein, we examined whether targeting the RAS-RAF-MEK-ERK pathway with the RAF
      inhibitor sorafenib and/or the PI3K-AKT-mTOR pathway with the mTOR inhibitor
      rapamycin has therapeutic effects against melanoma. A combination of sorafenib (4
      microM) with rapamycin (10 nM) potentiated growth inhibition in all six
      metastatic melanoma cell lines tested. The absolute enhancement of growth
      inhibition rates ranged from 13.0-27.8% in different cell lines (P<0.05,
      combination treatment vs monotreatment). Similar results were obtained with
      combinations of the MEK inhibitors U0126 (30 microM) or PD98059 (50 microM) with
      rapamycin (10 nM). The combined treatment of melanoma cells with sorafenib and
      rapamycin led to an approximately twofold increase of cell death compared with
      sorafenib monotreatment (P<0.05) as assessed by propidium iodide staining and
      cell death detection ELISA. Moreover, sorafenib in combination with rapamycin
      completely suppressed invasive melanoma growth in organotypic culture mimicking
      the physiological context. These effects were associated with complete
      downregulation of the antiapoptotic proteins Bcl-2 and Mcl-1. Sorafenib combined
      with rapamycin appears to be a promising strategy for the effective treatment of
      melanoma and merits clinical investigation.

PMID- 18323782
TI  - Distribution and significance of occult intraepidermal tumor cells surrounding
      primary melanoma.
AB  - Primary melanoma can recur at the excision site if not excised with a safety
      margin of surrounding uninvolved skin. To characterize the nature of residual
      melanoma in the skin surrounding primary tumors targeted by safety margins, we
      used array comparative genomic hybridization and fluorescent in situ
      hybridization to detect and spatially map aberrations in the skin adjacent to
      acral melanomas. Melanocytic cells with genetic amplifications in
      histopathologically normal skin (field cells) were detected exclusively in the
      epidermis in 84% of 19 cases, with a mean extension of 6.1 mm (in situ melanomas)
      and 4.5 mm (invasive melanomas) beyond the histopathological margin. Genetic
      profiling of these field cells indicated that they represent an early phase of
      disease preceding melanoma in situ. The extent of field cells did not correlate
      with tumor depth or diameter, indicating that tumor depth is not suited to
      predict the extent of field cells. These results demonstrate that, on acral
      sites, melanoma field cells extend significantly into seemingly normal skin.
      These field cells provide a plausible explanation for the tendency of certain
      melanoma types to recur locally despite apparently having undergone complete
      excision.

PMID- 18323783
TI  - Increased frequency of Ig heavy-chain HS1,2-A enhancer *2 allele in dermatitis
      herpetiformis, plaque psoriasis, and psoriatic arthritis.
AB  - The enhancer DNase-hypersensitive region 1,2 (HS1,2), a member of the Ig heavy
      chain 3' regulatory region (3'RR) cluster, is active in human B cells transfected
      with reporter genes and in mouse is activated in late maturation. HS1,2-A
      contains binding sites for several transcription factors. There are four known
      alleles, that is, (*)1, (*)2, (*)3, and (*)4, which differ in their lengths in
      transcription factor binding. We showed that in celiac disease the frequency of
      the (*)2 allele is increased. Both dermatitis herpetiformis (DH) and psoriasis
      can be associated with different frequencies with celiac disease. Thus, we
      further investigate the frequency of allele (*)2 in DH, plaque psoriatic, and
      psoriatic arthritis patients. HS1,2-A allele frequencies were investigated in 37
      DH, 61 plaque psoriatic, 28 psoriatic arthritis patients, and 265 healthy donors,
      age- and sex-matched, from the same geographical area. The frequency of the (*)2
      allele changes from 0.39 in controls to 0.63 in DH, 0.59 in plaque psoriasis and
      0.75 in psoriatic arthritis (P between 10(-4)-10(-5)). Our data evidence an
      increased frequency of the (*)2 allele of HS1,2-A in these cutaneous immune
      related disorders. We suggest a related genetic predisposition in these
      pathogeneses.

PMID- 18323784
TI  - Akt blockade downregulates collagen and upregulates MMP1 in human dermal
      fibroblasts.
AB  - Acutely transforming retrovirus AKT8 in rodent T-cell lymphoma (Akt) is a
      serine/threonine kinase that plays important roles in survival, cell-cycle
      progression, and cell proliferation, and has recently been implicated in collagen
      regulation. The aim of this study was to determine the role of Akt in collagen
      deposition by normal dermal fibroblasts, and to determine the sensitivity of
      cultured systemic sclerosis (SSc) fibroblasts to Akt inhibition. We show that
      blockade of Akt using pharmacological inhibitors, small interfering RNA (siRNA),
      and a dominant-negative Akt mutant led to inhibition of the basal type I collagen
      production. Furthermore, inhibition of Akt upregulated basal matrix
      metalloproteinase 1 (MMP1) production and reversed the inhibitory effect of
      transforming growth factor-beta (TGF-beta) on MMP1 gene expression. In addition,
      SSc fibroblasts were more sensitive to Akt inhibition, with respect to collagen
      and MMP1 production. These findings suggest that in human dermal fibroblasts, Akt
      has dual profibrotic effects, increasing collagen synthesis and decreasing its
      degradation via downregulation of MMP1. Akt could directly contribute to elevated
      collagen in SSc fibroblasts and it may represent an attractive target for therapy
      of SSc fibrosis.

PMID- 18323785
TI  - Microtubule-targeted drugs inhibit VEGF receptor-2 expression by both
      transcriptional and post-transcriptional mechanisms.
AB  - Cytoskeletal polymers control a wide range of cellular functions, including
      proliferation, migration, and gene expression. As changes in endothelial cell
      shape and motility are required to form vascular networks, we hypothesized that
      disassembly of actin filaments or microtubules may impact endothelial vascular
      endothelial growth factor (VEGF) receptor-2 (VEGFR2) expression as a critical
      determinant of angiogenesis. We therefore investigated the effect of actin
      filament- and microtubule-disrupting agents on VEGFR1 and VEGFR2 expression by
      endothelial cells. Microtubule (MT) disassembly greatly inhibited endothelial
      VEGFR2 expression, whereas VEGFR1 expression levels remained largely unchanged.
      These suppressive effects were neither conveyed by increased VEGFR2 shedding nor
      by shortened protein half-life, suggesting that transcriptional mechanisms
      account for the observed effects. In line with this conclusion, MT disruption
      significantly suppressed endothelial VEGFR2 mRNA accumulation. The treatment
      considerably decreased transcriptional activity of 5'-deletional VEGFR2 promoter
      gene constructs. MT disruption-mediated repression was conveyed by a GC-rich
      region harboring two consensus Sp1-binding sites. Electrophoretic mobility-shift
      assay analysis demonstrated that constitutive Sp1-dependent DNA binding is
      decreased by MT disassembly. In addition, we provide evidence for additional post
      transcriptional regulatory mechanisms, as the VEGFR2 mRNA half-life is
      significantly reduced by MT-disrupting agents. Hence, both inhibition of the rate
      of gene transcription and increased mRNA turnover represent critical molecular
      mechanisms by which MT disruption inhibits VEGFR2 expression.

PMID- 18323786
TI  - Profiling motility signal-specific genes in primary human keratinocytes.
AB  - Regulation of human keratinocyte (HK) migration is critical for skin wound
      healing. Profiling HK migration-specific genes could help us gain a comprehensive
      understanding of the process. The main challenge is to separate genes that are
      unrelated to migration, but simultaneously induced by the same growth factor. In
      this study, we took advantage of a unique response of HKs to transforming growth
      factor-beta (TGF-beta), which inhibits proliferation but not migration of HKs, to
      suppress selectively the proliferation-related genes. Furthermore we stimulated
      HKs independently with TGF-alpha or insulin and identified the common genes and
      eliminated TGF-alpha- or insulin-specific genes. Under these conditions, we
      obtained profiles of the immediate-early genes (IEGs, at 30 minutes), early genes
      (EGs, at 60 minutes), and delayed-early genes (DEGs, at 120 minutes) by
      microarray analyses, followed by quantitative real-time reverse transcription-PCR
      (QRT-PCR) validation and functional characterization by RNA interference (RNAi).
      Our results revealed the following: (1) 25 upregulated and 1 downregulated IEGs;
      (2) 58 upregulated and 15 downregulated EGs, and (3) 13 upregulated and 3
      downregulated DEGs in both TGF-alpha- and insulin-stimulated HKs. Three genes,
      all encoding secreted molecules, were investigated in HK migration. These cell
      motility-specific gene profiles may prove useful to skin wound healing.

PMID- 18323787
TI  - Phospho-ERK staining is a poor indicator of the mutational status of BRAF and
      NRAS in human melanoma.
AB  - Mutated BRAF and NRAS are suspected to contribute to melanomagenesis by
      activation of extracellular signal-regulated kinase (ERK). To test this notion,
      we analyzed the presence of phosphorylated ERK1/2 in 170 melanomas with
      established NRAS/BRAF mutational status and well-documented clinical follow-up by
      immunohistochemistry. Several notable observations were obtained: (i) phospho-ERK
      staining was very heterogeneous within the tumor; (ii) in most cases, ERK was
      phosphorylated in only a minority of tumor cells; (iii) the percentage of phospho
      ERK-positive cells was not correlated with the mutational status of NRAS and/or
      BRAF; (iv) the Raf kinase inhibitor protein (RKIP) was expressed homogeneously in
      virtually all melanoma samples not reflecting the inhomogeneity of phospho-ERK;
      and, finally, (v) neither the portion of phospho-ERK-positive tumor cells nor the
      RKIP staining intensity showed any correlation to the clinical course of the
      patients. Furthermore, the ability of BRAF mutant melanoma cells to downregulate
      mitogen-activated protein kinase activation was shown in melanoma cell lines
      cultured at high densities or under nonadherent conditions. Our findings suggest
      that mitogen-activated protein kinase (MAPK) activity is subject to regulation
      even in BRAF/NRAS mutant melanoma cells and that high MAPK pathway signaling may
      be important only in distinct subsets of tumor cells.

PMID- 18323788
TI  - Computer-based classification of dermoscopy images of melanocytic lesions on
      acral volar skin.
AB  - We describe a fully automated system for the classification of acral volar
      melanomas. We used a total of 213 acral dermoscopy images (176 nevi and 37
      melanomas). Our automatic tumor area extraction algorithm successfully extracted
      the tumor in 199 cases (169 nevi and 30 melanomas), and we developed a diagnostic
      classifier using these images. Our linear classifier achieved a sensitivity (SE)
      of 100%, a specificity (SP) of 95.9%, and an area under the receiver operating
      characteristic curve (AUC) of 0.993 using a leave-one-out cross-validation
      strategy (81.1% SE, 92.1% SP; considering 14 unsuccessful extraction cases as
      false classification). In addition, we developed three pattern detectors for
      typical dermoscopic structures such as parallel ridge, parallel furrow, and
      fibrillar patterns. These also achieved good detection accuracy as indicated by
      their AUC values: 0.985, 0.931, and 0.890, respectively. The features used in the
      melanoma-nevus classifier and the parallel ridge detector have significant
      overlap.

PMID- 18323789
TI  - Critical role of HIF-1alpha in keratinocyte defense against bacterial infection.
AB  - Skin, the first barrier against invading microorganisms, is hypoxic, even under
      baseline conditions. The transcription factor hypoxia-inducible factor-1alpha
      (HIF-1alpha, the principal regulator of cellular adaptation to low oxygen, is
      strongly expressed in skin epithelium. HIF-1alpha is now understood to play a key
      role in the bactericidal capacity of phagocytic cells such as macrophages and
      neutrophils. In the skin, keratinocytes provide a direct antibacterial activity
      through production of antimicrobial peptides, including cathelicidin. Here, we
      generate mice with a keratinocyte-specific deletion of HIF-1alpha and examine
      effects on intrinsic skin immunity. Keratinocyte HIF-1alpha is seen to provide
      protection against necrotic skin lesions produced by the pathogen group A
      Streptococcus. RNA interference studies reveal that HIF-1alpha regulation of
      keratinocyte cathelicidin production is critical to their antibacterial function.

PMID- 18323790
TI  - Adenovirus targeting to HLA-A1/MAGE-A1-positive tumor cells by fusing a single
      chain T-cell receptor with minor capsid protein IX.
AB  - Adenovirus vectors have great potential in cancer gene therapy. Targeting of
      cancer-testis (CT) antigens, which are specifically presented at the surface of
      tumor cells by human leukocyte antigen (HLA) class I molecules, is an attractive
      option. In this study, a single-chain T-cell receptor (scTCR) directed against
      the CT antigen melanoma-associated antigen (MAGE)-A1 in complex with the HLA
      class I molecule of haplotype HLA-A1 is fused with the C terminus of the
      adenovirus minor capsid protein IX. Propagation of a protein-IX (pIX)-gene
      deleted human adenovirus 5 (HAdV-5) vector on cells that constitutively express
      the pIXscTCR fusion protein yielded viral particles with the pIXscTCR fusion
      protein incorporated in their capsid. Generated particles specifically transduced
      melanoma cell lines expressing the HLA-A1/MAGE-A1 target complex with at least 10
      fold higher efficiency than control viruses. Whereas loading of HLA-A1-positive
      cells with MAGE-A1 peptides leads to enhanced transduction of the cells, the
      efficiency of virus transduction is strongly reduced if the HLA-A1 molecules are
      not accessible at the target cell. Taken together, these data provide proof of
      principle that pIXscTCR fusions can be used to target HAdV-5 vectors to tumor
      cells expressing intracellular CT antigens.

PMID- 18323791
TI  - Atelocollagen-mediated local and systemic applications of myostatin-targeting
      siRNA increase skeletal muscle mass.
AB  - RNA interference (RNAi) offers a novel therapeutic strategy based on the highly
      specific and efficient silencing of a target gene. Since it relies on small
      interfering RNAs (siRNAs), a major issue is the delivery of therapeutically
      active siRNAs into the target tissue/target cells in vivo. For safety reasons,
      strategies based on vector delivery may be of only limited clinical use. The more
      desirable approach is to directly apply active siRNAs in vivo. Here, we report
      the effectiveness of in vivo siRNA delivery into skeletal muscles of normal or
      diseased mice through nanoparticle formation of chemically unmodified siRNAs with
      atelocollagen (ATCOL). ATCOL-mediated local application of siRNA targeting
      myostatin, a negative regulator of skeletal muscle growth, in mouse skeletal
      muscles or intravenously, caused a marked increase in the muscle mass within a
      few weeks after application. These results imply that ATCOL-mediated application
      of siRNAs is a powerful tool for future therapeutic use for diseases including
      muscular atrophy.

PMID- 18323792
TI  - AAV-BDNF mediated attenuation of quinolinic acid-induced neuropathology and motor
      function impairment.
AB  - Maintenance and plasticity of striatal neurons is dependent on brain-derived
      neurotrophic factor (BDNF), which is depleted in the Huntington's disease
      striatum due to reduced expression and disrupted corticostriatal transportation.
      In this study we demonstrate that overexpression of BDNF in the striatum
      attenuates motor impairment and reduces the extent of striatal damage following
      quinolinic acid lesioning. Transfer of the BDNF gene to striatal neurons using
      serotype 1/2 adeno-associated viral vectors enhanced BDNF protein levels in the
      striatum, but induced weight loss and seizure activity following long-term high
      level expression. Lower concentration BDNF expression supported striatal neurons
      against excitotoxic insult, as demonstrated by enhanced krox-24 immunopositive
      neuron survival, reduction of striatal atrophy and maintenance of the
      patch/matrix organization. Additionally, BDNF expression attenuated motor
      impairment in the forelimb use cylinder test, sensorimotor neglect in the
      corridor food selection task and reversed apomorphine-induced rotational
      behaviour. Direct correlations were shown for the first time between BDNF
      mediated attenuation of behavioural impairment and the integrity of the globus
      pallidus, seemingly independent from the severity of striatal lesioning. These
      results demonstrate that BDNF holds considerable therapeutic potential for
      alleviating both neuropathological and motor function deficits in the
      Huntington's disease brain, and the critical role of pallidal neurons in
      facilitating motor performance.

PMID- 18323793
TI  - Characterization of the adaptive and innate immune response to intravenous
      oncolytic reovirus (Dearing type 3) during a phase I clinical trial.
AB  - There is an emerging realization from animal models that the immune response may
      have both detrimental and beneficial therapeutic effects during cancer
      virotherapy. However, there is a dearth of clinical data on the immune response
      to viral agents in patients. During a recently completed phase I trial of
      intravenous reovirus type 3 Dearing (RT3D), heavily pretreated patients with
      advanced cancers received RT3D at doses escalating from 1 x 10(8) tissue culture
      infectious dose-50 (TCID(50)) on day 1 to 3 x 10(10) TCID(50) on 5 consecutive
      days of a 4 weekly cycle. A detailed analysis of the immune effects was conducted
      by collecting serial clinical samples for analysis of neutralizing anti-reoviral
      antibodies (NARA), peripheral blood mononuclear cells (PBMC) and cytokines.
      Significant increases in NARA were seen with peak endpoint titres >1/10 000 in
      all but one patient. The median fold increase was 250, with a range of 9-6437.
      PBMC subset analysis showed marked heterogeneity. At baseline, CD3+CD4+ T cells
      were reduced in most patients, but after RT3D therapy their numbers increased in
      47.6% of patients. In contrast, most patients had high baseline CD3+CD8+ T-cell
      levels, with 33% showing incremental increases after therapy. In some patients,
      there was increased cytotoxic T-cell activation post-therapy, as shown by
      increased CD8+perforin/granzyme+ T-cell numbers. Most patients had high numbers
      of circulating CD3-CD56+ NK cells before therapy and in 28.6% this increased with
      treatment. Regulatory (CD3+CD4+CD25+) T cells were largely unaffected by the
      therapy. Combined Th1 and Th2 cytokine expression increased in 38% of patients.
      These data confirm that even heavily pretreated patients are capable of mounting
      dynamic immune responses during treatment with RT3D, although these responses are
      not clearly related to the administered virus dose. These data will provide the
      basis for future studies aiming to modulate the immune response during
      virotherapy.

PMID- 18323794
TI  - Improved lentiviral vectors for Wiskott-Aldrich syndrome gene therapy mimic
      endogenous expression profiles throughout haematopoiesis.
AB  - Wiskott-Aldrich syndrome (WAS) gene therapy requires highly efficient and well
      controlled vectors. Here we studied the performance of a lentiviral vector (LV)
      harbouring a 500-bp fragment of the WAS proximal promoter (WW), which we
      previously characterized as haematopoietic-specific and capable of restoring WAS
      phenotype in patients' T cells. We used an LV (WE) expressing eGFP to evaluate
      whether this promoter was following the expression pattern of endogenous WASp.
      Transgene expression was analysed in WE-transduced hCD34+ population and its
      progeny after in vitro and in vivo differentiation in the Rag2-/-, gammac-/-
      humanized mouse. We revealed very poor expression from the WE internal promoter
      in macrophages and erythroid cells. Therefore, we designed a novel LV including a
      fragment of the alternative WAS promoter in WE vector (AWE). This new vector
      sustained high transgene levels along the whole lymphoid lineage in vivo. Most
      importantly, the performance of AWE vector was highly superior to WE vector since
      AWE clearly improved transgene levels in in vitro and in vivo hCD34+-derived
      macrophages, erythroid cells, megakaryocytes and B cells while supporting a high
      expression in human T cells. This emphasizes that it is a suitable LV backbone
      for gene therapy of haematopoietic diseases such as WAS.

PMID- 18323795
TI  - Development of an enhanced B-specific lentiviral vector expressing BTK: a tool
      for gene therapy of XLA.
AB  - Further development of haematopoietic stem cell (HSC) gene therapy will depend on
      enhancement of gene transfer safety: ad hoc improvement of vector design relating
      to each particular disease is thus a crucial issue for HSC gene therapy. We
      modified a previously described lentiviral vector by adding the Emumar B-specific
      enhancer to a human CD19 promoter-derived sequence (Mol Ther 2004;10:45-56). We
      thus significantly improved the level of expression of the green fluorescent
      protein (GFP) reporter gene while retaining the specificity of expression in B
      cell progeny of transduced human CD34+ progenitor cells obtained from cord blood
      or adult bone marrow. Indeed, GFP was strongly expressed from early medullary pro
      B cells to splenic mature B cells whereas transgene expression remained low in
      transduced immature progenitors as in myeloid and T-lymphoid progeny retrieved
      from xenografted NOD/SCID/gammac(null) mice. Using this lentiviral vector, we
      further demonstrated the possibility to express a functional human BTK protein in
      long-term human CD34+ cell B-lymphoid progeny. This newly designed lentiviral
      vector fulfils one of the pre-requisites for the development of efficient and
      safe gene therapy for X-linked agammaglobulinaemia, the most common primary
      humoral immunodeficiency disorder.

PMID- 18323796
TI  - Experimental non-ATP-competitive therapies for chronic myelogenous leukemia.
AB  - Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy driven
      by the BCR-ABL fusion tyrosine kinase. The central role played by BCR-ABL1 in the
      pathogenesis of CML facilitated the development of the tyrosine kinase inhibitor
      (TKI) imatinib mesylate, the first actual targeted therapy in cancer history.
      Imatinib competes with ATP at the active site of BCR-ABL1 kinase. Despite
      outstanding clinical results, imatinib as well as other BCR-ABL1 TKIs have been
      associated with limited rates of complete molecular response and the development
      of mutations within the kinase domain of BCR-ABL1 that impairs TKI binding. To
      override such drawbacks, an array of novel non-ATP-competitive therapies with
      distinct mechanisms of action is undergoing preclinical, and in some cases, early
      clinical stages of development. This review focuses on the most promising among
      such therapeutics.

PMID- 18323797
TI  - Association between high expression of natural killer related-genes (NCAM/CD94)
      and early death during induction in children with acute myeloid leukemia.

PMID- 18323798
TI  - Meeting report: myelodysplastic syndromes at ASH 2007.
AB  - Myelodysplastic syndromes (MDS) remain challenging to both clinicians and
      biologists. This year's edition of the Annual Meeting of the American Society of
      Hematology has provided several breakthroughs in the biology and therapeutics of
      MDS, such as uncovering of the molecular genetics of the 5q- syndrome and clear
      evidence of a survival advantage with a hypomethylating agent in high-risk MDS.
      We summarize those advances and delineate some perspectives for these diseases.

PMID- 18323799
TI  - MAGE-C1/CT7 is the dominant cancer-testis antigen targeted by humoral immune
      responses in patients with multiple myeloma.

PMID- 18323800
TI  - Identification of marker genes including RUNX3 (AML2) that discriminate between
      different myeloproliferative neoplasms and normal individuals.

PMID- 18323801
TI  - MicroRNAs and noncoding RNAs in hematological malignancies: molecular, clinical
      and therapeutic implications.
AB  - MicroRNAs (miRNAs) are a family of 19-24 nucleotide noncoding RNAs (ncRNAs) with
      posttranscriptional regulatory functions. Increasing evidences from the
      literature show that miRNAs play a pivotal role in human tumorigenesis. Many
      studies have addressed the role of miRNAs in normal hematopoiesis, giving an
      interpretative key to the aberrancies of expression observed in human
      hematological malignancies. Moreover, the recent demonstration that other ncRNAs,
      the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs),
      are involved in human cancerogenesis, suggests that the wider family of ncRNAs
      (including both miRNAs and UCGs) could contribute to the development of the
      malignant phenotype. Here we review the main studies investigating the role of
      miRNAs and UCRs in both normal hemopoiesis and hematological malignancies, and
      identify the molecular, clinical and therapeutic implications of these recent
      findings.

PMID- 18323802
TI  - Vaccination of B-CLL patients with autologous dendritic cells can change the
      frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+
      regulatory T cells toward an antileukemia response.
AB  - Recently, we described that vaccination with allogeneic dendritic cells (DCs)
      pulsed with tumor cell lysate generated specific CD8+ T cell response in patients
      with B-cell chronic lymphocytic leukemia (B-CLL). In the present study, the
      potential of autologous DCs pulsed ex vivo with tumor cell lysates to stimulate
      antitumor immunity in patients with B-CLL in early stages was evaluated. Twelve
      patients at clinical stage 0-2 as per Rai were vaccinated intradermally up to
      eight times with a mean number of 7.4 x 10(6) DCs pulsed with B-CLL cell lysate.
      We observed a decrease of peripheral blood leukocytes and CD19+/CD5+ leukemic
      cells in five patients, three patients showed a stable disease and four patients
      progressed despite DC vaccination. A significant increase of specific cytotoxic
      CD8+ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin
      was detected in four patients after DC vaccination. In patients with a clinical
      response, an increase of interleukin 12 (IL-12) serum levels and a decrease of
      the frequency of CD4+CD25(+)FOXP3+ T regulatory cells were observed. Taken
      together, the study demonstrated that vaccination with autologous DC in CLL
      patients is feasible and safe. Immunological and to some extend hematological
      responses could be noted, justifying further investigation on this
      immunotherapeutical approach.

PMID- 18323803
TI  - T-cell receptor Vbeta CDR3 oligoclonality frequently occurs in childhood
      refractory cytopenia (MDS-RC) and severe aplastic anemia.
AB  - (Very) severe acquired aplastic anemia ((v)SAA) and myelodysplastic syndrome
      (MDS) are rare diseases in childhood. (V)SAA is a bone marrow (BM) failure
      syndrome characterized by immune-mediated destruction of hematopoietic
      progenitors. MDS is a malignant clonal stem cell disorder, of which the
      hypoplastic variant is, in case of absence of a cytogenetic clone, difficult to
      separate from (v)SAA. Recently, studies provided a molecular signature of
      autoimmunity in adult (v)SAA, by showing oligoclonality based on the length of
      the TCR Vbeta CDR3 region. We investigated retrospectively the frequency and the
      discriminative value of TCR Vbeta CDR3 oligoclonality in pediatric (v)SAA and MDS
      patients. Peripheral blood (PB) and/or BM mononuclear cell samples of pediatric
      patients with (v)SAA (n=38), refractory cytopenia (MDS-RC) (n=28) and 18 controls
      were analysed via TCR Vbeta heteroduplex PCR analysis of extracted RNA. A skewed
      TCR Vbeta CDR3 repertoire was found in 21/38 (v)SAA and in 17/28 RC patients in
      contrast to 2/18 in the control group. These data suggest an overlapping group of
      RC and SAA patients that may share a common immune-mediated pathogenesis.
      Prospective studies are required to establish the clinical value of TCR Vbeta
      CDR3 repertoire analysis to predict the clinical response in these patients.

PMID- 18323804
TI  - Preparation of magnetic resonance contrast agents activated by beta
      galactosidase.
AB  - The preparation of beta-EgadMe and alpha-EgadMe, magnetic resonance (MR) contrast
      agents that can be used for in vivo detection of beta-galactosidase, is
      described. Diastereomerically pure beta-EgadMe can be synthesized by kinetically
      resolving the starting material as described in Step 1. The total time for the
      preparation of the racemic mixture of beta-EgadMe is about 8 d, and the total
      time for an diastereomerically resolved agent is about 9 d. The final metallated
      agent is stable at room temperature as a solid or in aqueous buffer (pH 5.5-10)
      indefinitely. Diastereomerically pure alpha-EgadMe can be prepared by beginning
      the synthesis with enantiomerically pure bromopropionic acid. The total time for
      the preparation of racemic alpha-EgadMe or diastereomerically pure alpha-EgadMe
      is about 8 d. The final metallated agent is stable at room temperature as a solid
      or in aqueous buffer (pH 5.5-10) indefinitely.

PMID- 18323805
TI  - An ESI-MS method for characterization of native and modified oligonucleotides
      used for RNA interference and other biological applications.
AB  - RNA interference (RNAi) has become a powerful tool for investigating gene
      function, and, in addition, shows potential for the development of therapeutic
      agents. RNAi can be triggered in a variety of eukaryotic cells using small
      interfering RNA (siRNA), their double-stranded precursors (double-stranded RNA)
      and short hairpin precursors (shRNA). Here, we describe a protocol for analyzing
      these RNAs and their modifications using electrospray ionization mass
      spectrometry (ESI-MS). This protocol involves the desalting of nucleic acids
      using ammonium acetate precipitation, followed by characterization using ESI-MS.
      This protocol has been chiefly used for analyzing siRNAs and their chemical
      modifications, but it has also been used and can be applied to the analysis of a
      wide range of native and modified oligonucleotides. This protocol provides
      accurate information on molecular weight for a range of nucleic acids and can be
      completed in less than a day.

PMID- 18323806
TI  - A high-throughput fluorescence-based glycosyltransferase screen and its
      application in directed evolution.
AB  - This protocol details the application of a high-throughput fluorescence-based
      screen, in conjunction with error-prone PCR/saturation mutagenesis, for altering
      the proficiency and/or promiscuity of a secondary metabolite glycosyltransferase
      (GT) via directed evolution. Given the structural and mechanistic similarities
      among secondary metabolite-associated GTs, this approach may provide a template
      for engineering other members of the GT-B superfamily.

PMID- 18323807
TI  - Isolation and propagation of HIV-1 on peripheral blood mononuclear cells.
AB  - Human immunodeficiency virus type 1 (HIV-1) infection is characterized by a
      gradual loss of CD4+ T cells and T-cell function and an ongoing high level of
      virus replication. The high replication rate and the error-prone nature of HIV-1
      reverse transcriptase create a diverse viral quasispecies throughout infection.
      To study biological properties of HIV-1 quasispecies in relation to the clinical
      course of infection, the in vitro preservation of phenotypical characteristics of
      the virus is essential. Here, we describe the method for bulk isolation of the
      HIV-1 quasispecies and a limiting dilution virus isolation protocol by which
      single coexisting HIV-1 variants can be obtained using peripheral blood
      mononuclear cells from a healthy donor as target cells. In addition, methods for
      propagation and titration of HIV-1 are provided.

PMID- 18323808
TI  - Selective isolation of genomic loci from complex genomes by transformation
      associated recombination cloning in the yeast Saccharomyces cerevisiae.
AB  - Here, we describe a protocol for the selective isolation of any genomic fragment
      or gene of interest up to 250 kb in size from complex genomes as a circular yeast
      artificial chromosome (YAC). The method is based on transformation-associated
      recombination (TAR) in the yeast Saccharomyces cerevisiae between genomic DNA and
      a linearized TAR cloning vector containing targeting sequences homologous to a
      region of interest. Recombination between the vector and homologous sequences in
      the co-transformed mammalian DNA results in the establishment of a YAC that is
      able to propagate, segregate and be selected for in yeast. Yield of gene-positive
      clones varies from 1% to 5%. The entire procedure takes 2 weeks to complete once
      the TAR vector is constructed and genomic DNA is prepared. The TAR cloning method
      has a broad application in functional and comparative genomics, long-range
      haplotyping and characterization of chromosomal rearrangements, including copy
      number variations.

PMID- 18323809
TI  - A protocol for a lung neovascularization model in rodents.
AB  - By providing insight into the cellular events of vascular injury and repair,
      experimental model systems seek to promote timely therapeutic strategies for
      human disease. The goal of many current studies of neovascularization is to
      identify cells critical to the process and their role in vascular channel
      assembly. We propose here a protocol to analyze, in an in vivo rodent model,
      vessel and capillary remodeling (reorganization and growth) in the injured lung.
      Sequential analyses of stages in the assembly of vascular structures, and of
      relevant cell types, provide further opportunities to study the molecular and
      cellular determinants of lung neovascularization.

PMID- 18323810
TI  - A protocol for phenotypic detection and characterization of vascular cells of
      different origins in a lung neovascularization model in rodents.
AB  - The goal of many current studies of neovascularization is to define the phenotype
      of vascular cell populations of different origins and to determine how such cells
      promote assembly of vascular channel. Here, we describe a protocol to
      immunophenotype vascular cells by high-resolution imaging and by fluorescence
      activated flow cytometry in an in vivo rodent model of pulmonary microvascular
      remodeling. Analysis of cells by this combined approach will characterize their
      phenotype, quantify their number and identify their role in the assembly of
      vascular channels.

PMID- 18323811
TI  - Analysis of epigenetic modifications of chromatin at specific gene loci by native
      chromatin immunoprecipitation of nucleosomes isolated using hydroxyapatite
      chromatography.
AB  - Chromatin immunoprecipitation (ChIP) is routinely used to examine epigenetic
      modification of histones at specific genomic locations. However, covalent
      modifications of histone tails can serve as docking sites for chromatin
      regulatory factors. As such, association of these regulatory factors with
      chromatin could cause steric hindrance for antibody recognition, resulting in an
      underestimation of the relative enrichment of a given histone modification at
      specific loci. To overcome this problem, we have developed a native ChIP protocol
      to study covalent modification of histones that takes advantage of hydroxyapatite
      (HAP) chromatography to wash away chromatin-associated proteins before the
      immunoprecipitation of nucleosomes. This fast and simple procedure consists of
      five steps: nuclei isolation from cultured cells; fragmentation of chromatin
      using MNase; purification of nucleosomes using HAP; immunoprecipitation of
      modified nucleosomes; and qPCR analysis of DNA associated with modified histones.
      Nucleosomes prepared in this manner are free of contaminating proteins and permit
      an accurate evaluation of relative abundance of different covalent histone
      modifications at specific genomic loci. Completion of this protocol requires
      approximately 1.5 d.

PMID- 18323812
TI  - High-efficiency transformation by biolistics of soybean, common bean and cotton
      transgenic plants.
AB  - This protocol describes a method for high-frequency recovery of transgenic
      soybean, bean and cotton plants, by combining resistance to the herbicide
      imazapyr as a selectable marker, multiple shoot induction from embryonic axes of
      mature seeds and biolistics techniques. This protocol involves the following
      stages: plasmid design, preparation of soybean, common bean and cotton apical
      meristems for bombardment, microparticle-coated DNA bombardment of apical
      meristems and in vitro culture and selection of transgenic plants. The average
      frequencies (the total number of fertile transgenic plants divided by the total
      number of bombarded embryonic axes) of producing germline transgenic soybean and
      bean and cotton plants using this protocol are 9, 2.7 and 0.55%, respectively.
      This protocol is suitable for studies of gene function as well as the production
      of transgenic cultivars carrying different traits for breeding programs. This
      protocol can be completed in 7-10 months.

PMID- 18323813
TI  - Spatially and temporally controlled electroporation of early chick embryos.
AB  - The introduction of in ovo electroporation a decade ago has helped the chick
      embryo to become a powerful system to study gene regulation and function during
      development. Although this is a simple procedure for embryos of 2-d incubation,
      earlier stages (from laying to early neurulation, 0-1 d) present special
      challenges. Here we describe a robust and reproducible protocol for
      electroporation of expression vectors and morpholino oligonucleotides into the
      epiblast of embryos from soon after laying (stage XI) to stages 6-7 (early
      neurulation), with precise spatial and temporal control. Within 3 h, about 12
      embryos can be electroporated and set up for culture by the New technique; the
      effects of morpholinos can be assessed immediately after electroporation, and
      robust overexpression from plasmid DNA is seen 2-3 h after electroporation. These
      techniques can be used for time-lapse imaging, gain- and loss-of-function
      experiments and studying gene regulatory elements in living embryos.

PMID- 18323814
TI  - Tetrazolium-based colorimetric assay for the detection of HIV replication
      inhibitors: revisited 20 years later.
AB  - Since its first description 20 years ago, the tetrazolium-based colorimetric
      (MTT) assay using MT-4 cells for the detection of anti-HIV compounds has been
      widely used. This method, which remains popular, provides more information than
      more recently developed methods and, therefore, represents a useful methodology
      on its own or in combination with other screening systems. The replication of HIV
      in MT-4 cells is usually monitored 5 d after infection; therefore, this protocol
      can be divided into three steps: the infection (at day 0), an incubation period
      (5 d) and the evaluation (at day 5). The long-standing and intensive use of the
      MTT method has taught users of the limitations and, equally importantly, the
      unexpected advantages of the MT-4/MTT assay. The use of this method can be
      extended to antiviral testing of compounds against other cyto-destructive
      viruses.

PMID- 18323815
TI  - Rice blast infection of Brachypodium distachyon as a model system to study
      dynamic host/pathogen interactions.
AB  - Interactions between plants and compatible fungal pathogens are spatially and
      temporally dynamic, posing a major challenge for sampling and data analysis. A
      protocol is described for the infection of the model grass species Brachypodium
      distachyon with Magnaporthe grisea (rice blast), together with modifications to
      extend the use to rice and barley. We outline a method for the preparation of
      long-term stocks of virulent fungal pathogens and for the generation of fungal
      inoculants for challenge of host plants. Host plant growth, pathogen inoculation
      and plant sampling protocols are presented together with methods for assessing
      the efficiency of both infection and sampling procedures. Included in the
      anticipated results is a description of the use of metabolite fingerprinting and
      multivariate data analysis to assess disease synchrony and validate system
      reproducibility between experiments. The design concepts will have value in any
      studies using biological systems that contain dynamic variance associated with
      large compositional changes in sample matrix over time.

PMID- 18323816
TI  - Preprocessing, classification modeling and feature selection using flow injection
      electrospray mass spectrometry metabolite fingerprint data.
AB  - Metabolome analysis by flow injection electrospray mass spectrometry (FIE-MS)
      fingerprinting generates measurements relating to large numbers of m/z signals.
      Such data sets often exhibit high variance with a paucity of replicates, thus
      providing a challenge for data mining. We describe data preprocessing and
      modeling methods that have proved reliable in projects involving samples from a
      range of organisms. The protocols interact with software resources specifically
      for metabolomics provided in a Web-accessible data analysis package FIEmspro
      (http://users.aber.ac.uk/jhd) written in the R environment and requiring a
      moderate knowledge of R command-line usage. Specific emphasis is placed on
      describing the outcome of modeling experiments using FIE-MS data that require
      further preprocessing to improve quality. The salient features of both poor and
      robust (i.e., highly generalizable) multivariate models are outlined together
      with advice on validating classifiers and avoiding false discovery when seeking
      explanatory variables.

PMID- 18323817
TI  - Explanatory signal interpretation and metabolite identification strategies for
      nominal mass FIE-MS metabolite fingerprints.
AB  - Flow injection electrospray mass spectrometry (FIE-MS) metabolite fingerprinting
      is widely used as a 'first pass' screen for compositional differences, where
      discrimination between samples can be achieved without any preconceptions.
      Powerful data analysis algorithms can be used to select and rank FIE-MS
      fingerprint variables highly explanatory of the biological problem under
      investigation. We describe how to create a species-specific FIE-MS/MS(n)
      metabolite database and how to then query the database to predict the identity of
      highly significant variables within FIE-MS fingerprints. The protocol details how
      to interpret m/z signals within the explanatory variable list based on a
      correlation analysis in conjunction with an investigation of mathematical
      relationships regarding (de)protonated molecular ions, salt adducts, neutral
      losses and dimeric associations routinely observed in FIE-MS fingerprints.
      Although designed for use by biologists/analytical chemists, collaboration with
      data-mining experts is generally advised. The protocol is applicable in any areas
      of bioscience research involving FIE-MS fingerprinting.

PMID- 18323818
TI  - High-throughput, nontargeted metabolite fingerprinting using nominal mass flow
      injection electrospray mass spectrometry.
AB  - Flow injection electrospray-mass spectrometry (FIE-MS) is finding utility as a
      first-pass metabolite fingerprinting tool in many research fields. We provide a
      protocol that has proved reliable in large-scale research projects involving
      diverse sample matrices originating from plants, microbes and mammalian
      biofluids. Using Brachypodium leaf material as an example matrix all steps are
      summarized from sample extraction to data quality assessment. Alternative
      procedures for dealing with other common matrices such as bloods and urine are
      included. With little sample pretreatment, no chromatography and instrument cycle
      times of <5 min it is feasible to analyze >1,000 samples per week. Analysis of a
      typical batch of 240 samples (including first-pass data analysis) can be
      accomplished within 48 h.

PMID- 18323819
TI  - Quantitative proteomics using stable isotope labeling with amino acids in cell
      culture.
AB  - Stable isotope labeling with amino acids in cell culture (SILAC) is a simple in
      vivo labeling strategy for mass spectrometry-based quantitative proteomics. It
      relies on the metabolic incorporation of nonradioactive heavy isotopic forms of
      amino acids into cellular proteins, which can be readily distinguished in a mass
      spectrometer. As the samples are mixed before processing in the SILAC
      methodology, the sample handling errors are also minimized. Here we present
      protocols for using SILAC in the following types of experiments: (i) studying
      inducible protein complexes, (ii) identification of Tyr kinase substrates, (iii)
      differential membrane proteomics and (iv) studying temporal dynamics using SILAC
      5-plexing. Although the overall time is largely dependent on the rate of cell
      growth and various sample processing steps employed, a typical SILAC experiment
      from start to finish, including data analysis, should take anywhere between 20
      and 25 d.

PMID- 18323820
TI  - Ambient molecular imaging by desorption electrospray ionization mass
      spectrometry.
AB  - Desorption electrospray ionization (DESI) allows the direct analysis of ordinary
      objects or pre-processed samples under ambient conditions. Among other
      applications, DESI is used to identify and record spatial distributions of lipids
      and drug molecules in biological tissue sections. This technique does not require
      sample preparation other than production of microtome tissue slices and does not
      involve the use of ionization matrices. This greatly simplifies the procedure and
      prevents the redistribution of analytes during matrix deposition. Images are
      obtained by continuously moving the sample relative to the DESI sprayer and the
      inlet of the mass spectrometer. The timing of the protocol depends on the size of
      the surface to be analyzed and on the desired resolution. Analysis of organ
      tissue slices at 250 microm resolution typically takes between 30 min and 2 h.

PMID- 18323821
TI  - Purification of human plasma fibronectin using immobilized gelatin and Arg
      affinity chromatography.
AB  - This protocol describes a method for purification of fibronectin (Fn) from human
      plasma based on a combination of gel filtration and affinity chromatography
      steps. Clarified plasma is first loaded onto a Sepharose CL-4B column and unbound
      material is sequentially purified on columns containing covalently coupled
      gelatin and Arg. The elution conditions are optimized to obtain a homogeneous
      preparation of Fn on sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      (SDS-PAGE). Although the Fn yield is expected to be lower than that obtained
      using other methods, affinity adsorbents based on gelatin and Arg and gentle
      elution steps offer advantages including a high purity of the preparation and a
      correctly folded protein. The preparation can be useful for interaction studies
      and analysis of biological and immunological activities of Fn.

PMID- 18323822
TI  - Imaging proteins in live mammalian cells with biotin ligase and monovalent
      streptavidin.
AB  - This protocol describes a simple and efficient way to label specific cell surface
      proteins with biophysical probes on mammalian cells. Cell surface proteins tagged
      with a 15-amino acid peptide are biotinylated by Escherichia coli biotin ligase
      (BirA), whereas endogenous proteins are not modified. The biotin group then
      allows sensitive and stable binding by streptavidin conjugates. This protocol
      describes the optimal use of BirA and streptavidin for site-specific labeling and
      also how to produce BirA and monovalent streptavidin. Streptavidin is tetravalent
      and the cross-linking of biotinylated targets disrupts many of streptavidin's
      applications. Monovalent streptavidin has only a single functional biotin-binding
      site, but retains the femtomolar affinity, low off-rate and high thermostability
      of wild-type streptavidin. Site-specific biotinylation and streptavidin staining
      take only a few minutes, while expression of BirA takes 4 d and expression of
      monovalent streptavidin takes 8 d.

PMID- 18323823
TI  - Preparative scale Baeyer-Villiger biooxidation at high concentration using
      recombinant Escherichia coli and in situ substrate feeding and product removal
      process.
AB  - An efficient biocatalytic process based on the use of adsorbent resin (in situ
      substrate feeding and product removal) makes experiments at high substrate
      concentration possible by overcoming limitations due to substrate and product
      inhibition. This process was successfully applied to the preparative scale Baeyer
      Villiger biooxidation of (-)-(1S,5R)-bicyclo[3.2.0]hept-2-en-6-one (25 g). Whole
      cells of recombinant E. coli (1 liter) overexpressing cyclohexanone monooxygenase
      were used as a biocatalyst and the substrate was preloaded onto the adsorbent
      resin. The corresponding lactone was obtained in 75-80% yield. Time for cell
      growth and biotransformation is about 24 h each and oxygen supply can be improved
      by using a tailor-made bubble column.

PMID- 18323824
TI  - Getting with the program.
AB  - An Institute of Medicine report recommends that the United States government
      create a program to provide consistent guidelines for clinical interventions. The
      reliability of the guidelines will depend on the availability of the clinical
      data to be assessed.

PMID- 18323825
TI  - As demand for organs expands, so does transplant technology.

PMID- 18323826
TI  - Despite potential side effects, two drugs make a comeback.

PMID- 18323827
TI  - New plan proposed to help resolve conflicting medical advice.

PMID- 18323828
TI  - Swiss stance on HIV transmission sparks concern.

PMID- 18323829
TI  - India continues crackdown, dismissing hundreds of AIDS groups.

PMID- 18323831
TI  - The fight of your life.

PMID- 18323832
TI  - A matter of the heart.

PMID- 18323833
TI  - Q & A: Anna Veiga. Interviewed by Doug Sipp.

PMID- 18323834
TI  - No effect of endogenous TRIM5alpha on HIV-1 production.

PMID- 18323838
TI  - Animal experiments "represent outdated science".

PMID- 18323839
TI  - Laboratory animals deserve better legal protection.

PMID- 18323841
TI  - Taking two cuts at pain.

PMID- 18323842
TI  - The weakness of a big heart.

PMID- 18323843
TI  - Notch inhibition reverses kidney failure.

PMID- 18323844
TI  - Interleukin-22: a sheep in wolf's clothing.

PMID- 18323845
TI  - Reducing glutamate signaling pays off in fragile X.

PMID- 18323848
TI  - Cell-division inhibitors: new insights for future antibiotics.
AB  - The growing problem of antibiotic resistance has been exacerbated by the use of
      new drugs that are merely variants of older overused antibiotics. While it is
      naive to expect to restrain the spread of resistance without controlling
      antibacterial usage, the desperate need for drugs with novel targets has been
      recognized by health organizations, industry and academia alike. The wealth of
      knowledge available about the bacterial cell-division pathway has aided target
      driven approaches to identify novel inhibitors. Here, we discuss the therapeutic
      potential of inhibiting bacterial cell division, and review the progress made in
      this exciting new area of antibacterial discovery.

PMID- 18323849
TI  - Targeting melanocortin receptors: an approach to treat weight disorders and
      sexual dysfunction.
AB  - The melanocortin system has multifaceted roles in the control of body weight
      homeostasis, sexual behaviour and autonomic functions, and so targeting this
      pathway has immense promise for drug discovery across multiple therapeutic areas.
      In this Review, we first outline the physiological roles of the melanocortin
      system, then discuss the potential of targeting melanocortin receptors by using
      MC3 and MC4 agonists for treating weight disorders and sexual dysfunction, and
      MC4 antagonists to treat anorectic and cachectic conditions. Given the complexity
      of the melanocortin system, we also highlight the challenges and opportunities
      for future drug discovery in this area.

PMID- 18323850
TI  - Uncertainty in the niches that maintain haematopoietic stem cells.
AB  - Haematopoietic stem cell (HSC) niches are specialized microenvironments that
      contain stem cells and regulate their maintenance. Cells at the interface of bone
      and the bone marrow (the endosteum) contribute to the creation of HSC niches. It
      remains uncertain whether this interface itself is a niche, or whether endosteal
      cells secrete factors that diffuse to nearby niches. Vascular and/or perivascular
      cells may also create niches as many HSCs are observed around sinusoidal blood
      vessels, and perivascular cells secrete factors that regulate HSC maintenance. Do
      endosteal and perivascular cells create distinct niches, or do they contribute to
      a common niche? We discuss a range of niche models consistent with recent
      evidence.

PMID- 18323851
TI  - T-cell quality in memory and protection: implications for vaccine design.
AB  - T cells mediate effector functions through a variety of mechanisms. Recently,
      multiparameter flow cytometry has allowed a simultaneous assessment of the
      phenotype and multiple effector functions of single T cells; the delineation of T
      cells into distinct functional populations defines the quality of the response.
      New evidence suggests that the quality of T-cell responses is crucial for
      determining the disease outcome to various infections. This Review highlights the
      importance of using multiparameter flow cytometry to better understand the
      functional capacity of effector and memory T-cell responses, thereby enabling the
      development of preventative and therapeutic vaccine strategies for infections.

PMID- 18323852
TI  - Expression-targeted gene therapy for the treatment of transitional cell
      carcinoma.
AB  - Targeted gene delivery for induced apoptosis of transitional cell carcinomas was
      carried out in vivo in mice via utilization of the murine cyclooxygenase type 2
      (Cox-2) promoter (Tis10). MB49 cells, which constitutively overexpress Cox-2 like
      numerous other carcinomas, selectively expressed delivered genes that utilized
      this transcriptional control element. The products of the delivered genes were
      artificially inducible forms of caspases 3 and 9, which remained inactive until a
      chemical inducer of dimerization was later injected intraperitoneally. The genes
      were delivered intravesically as plasmids complexed with poly(ethylenimine).
      Significant improvements, in the form of reduced bladder mass, reduced tumor
      volume, anti-angiogenesis and inhibition of tumor growth were seen versus
      untreated or unactivated controls. In some instances, tumors were seen to go into
      complete remission. There were no apparent bystander effects associated with the
      treatments. This targeted gene therapy regimen could have wide applicability to
      numerous cancers due to constitutive overexpression of Cox-2.

PMID- 18323853
TI  - A cancer terminator virus eradicates both primary and distant human melanomas.
AB  - The prognosis and response to conventional therapies of malignant melanoma
      inversely correlate with disease progression. With increasing thickness,
      melanomas acquire metastatic potential and become inherently resistant to
      radiotherapy and chemotherapy. These harsh realities mandate the design of
      improved therapeutic modalities, especially those targeting metastases. To
      develop an approach to effectively treat this aggressive disease, we constructed
      a conditionally replication-competent adenovirus in which expression of the
      adenoviral E1A gene, necessary for replication, is driven by the cancer-specific
      promoter of progression-elevated gene-3 (PEG-3) and which simultaneously
      expresses mda-7/IL-24 in the E3 region of the adenovirus (Ad.PEG-E1A-mda-7), a
      cancer terminator virus (CTV). This CTV produces large quantities of MDA-7/IL-24
      protein as a function of adenovirus replication uniquely in cancer cells.
      Infection of Ad.PEG-E1A-mda-7 (CTV) in normal human immortal melanocytes and
      human melanoma cells demonstrates cancer cell-selective adenoviral replication,
      mda-7/IL-24 expression, growth inhibition and apoptosis induction. Injecting
      Ad.PEG-E1A-mda-7 CTV into xenografts derived from MeWo human metastatic melanoma
      cells in athymic nude mice completely eliminated not only primary treated tumors
      but also distant non-treated tumors (established in the opposite flank), thereby
      implementing a cure. These provocative findings advocate potential therapeutic
      applications of this novel virus for treating patients with advanced melanomas
      with metastases.

PMID- 18323854
TI  - The physiology and pathology of the EMT. Meeting on the epithelial-mesenchymal
      transition.

PMID- 18323855
TI  - Formation of a new receptor-operated channel by heteromeric assembly of TRPP2 and
      TRPC1 subunits.
AB  - Although several protein-protein interactions have been reported between
      transient receptor potential (TRP) channels, they are all known to occur
      exclusively between members of the same group. The only intergroup interaction
      described so far is that of TRPP2 and TRPC1; however, the significance of this
      interaction is unknown. Here, we show that TRPP2 and TRPC1 assemble to form a
      channel with a unique constellation of new and TRPP2/TRPC1-specific properties.
      TRPP2/TRPC1 is activated in response to G-protein-coupled receptor activation and
      shows a pattern of single-channel conductance, amiloride sensitivity and ion
      permeability distinct from that of TRPP2 or TRPC1 alone. Native TRPP2/TRPC1
      activity is shown in kidney cells by complementary gain-of-function and loss-of
      function experiments, and its existence under physiological conditions is
      supported by colocalization at the primary cilium and by co-immunoprecipitation
      from kidney membranes. Identification of the heteromultimeric TRPP2/TRPC1 channel
      has implications in mechanosensation and cilium-based Ca(2+) signalling.

PMID- 18323856
TI  - The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction.
AB  - The brain-specific synaptic guanosine triphosphatase (GTPase)-activating protein
      (SynGAP) is important in synaptic plasticity. It shows dual specificity for the
      small guanine nucleotide-binding proteins Rap and Ras. Here, we show that RapGAP
      activity of SynGAP requires its C2 domain. In contrast to the isolated GAP
      domain, which does not show any detectable RapGAP activity, a fragment comprising
      the C2 and GAP domains (C2-GAP) stimulates the intrinsic GTPase reaction of Rap
      by approximately 1 x 10(4). The C2-GAP crystal structure, complemented by
      modelling and biochemical analyses, favours a concerted movement of the C2 domain
      towards the switch II region of Rap to assist in GTPase stimulation. Our data
      support a catalytic mechanism similar to that of canonical RasGAPs and distinct
      from the canonical RapGAPs. SynGAP presents the first example, to our knowledge,
      of a GAP that uses a second domain for catalytic activity, thus pointing to a new
      function of C2 domains.

PMID- 18323857
TI  - NEDD8 acts as a 'molecular switch' defining the functional selectivity of VHL.
AB  - The von Hippel-Lindau (VHL) tumour suppressor protein is important in the E3
      ubiquitin ligase ECV (Elongin B/C-CUL2-VHL)-mediated destruction of hypoxia
      inducible factor and the promotion of fibronectin (FN) extracellular matrix
      assembly. Although the precise molecular mechanism controlling the selectivity of
      VHL function remains unknown, a failure in either process is associated with
      oncogenic progression. Here, we show that VHL performs its FN-associated function
      independently of the ECV complex, highlighting the autonomy of these pathways.
      Furthermore, we show that NEDD8, a ubiquitin-like molecule, acts as a 'molecular
      switch' in which its covalent conjugation to VHL prohibits the engagement of the
      scaffold component CUL2 and, concomitantly, activates the association with FN.
      These findings provide the first mechanistic step in defining the functional
      selectivity of VHL and explain a previously unrecognized function of NEDD8.

PMID- 18323858
TI  - Role of a functional human gene polymorphism in stress responsivity and
      addictions.
AB  - Over the past decade, enormous progress has been made in both the technical
      approaches and the scientific information available for studying the human
      genome. Therefore, increasingly, scientists have begun to address not just single
      gene disorders but complex disorders. The limiting factor in most of such studies
      remains appropriate, well-focused detailed phenotyping of the complex disorders
      under study, with careful ascertainment of subjects with the specific disorder,
      as well as healthy control subjects.

PMID- 18323859
TI  - Anticipating clinical integration of pharmacogenetic treatment strategies for
      addiction: are primary care physicians ready?
AB  - Emerging pharmacogenomics research on addiction to nicotine, alcohol, cocaine,
      and opiates may soon lead to improved clinical outcomes by tailoring the type,
      dose and duration of treatment to individual patients' genotypes. To realize the
      potential of pharmacogenomics in reducing the burden of addiction, several
      challenges related to clinical integration of novel treatment strategies will
      need to be addressed concomitantly with ongoing empirical research. These
      challenges include the preparedness of primary care physicians (PCPs) to
      incorporate pharmacogenetics into clinical practice, patients' willingness to
      undergo genetic testing, the resources and infrastructure needed to deliver such
      services, adequate financing and reimbursement of pharmacogenetic testing, and
      privacy and antidiscrimination protections sufficient to reassure physicians and
      patients that genetic testing will not lead to stigmatization and discrimination.

PMID- 18323860
TI  - Animal studies in the development of medical countermeasures.
AB  - The mission of the US Food and Drug Administration (FDA) is to protect public
      health by ensuring the safety, efficacy, and quality of drugs. In drug
      development, animal studies play a key role in assessing the safety (toxicology),
      pharmacokinetics (PK), and proof-of-concept efficacy of a new product. When
      clinical studies are neither ethical nor feasible to conduct, the Animal Rule (67
      FR 37988, 2002) introduces the potential for drug (e.g., countermeasure) approval
      based on efficacy studies in animals, and appropriate human safety and
      pharmacokinetic information. The Center for Drug Evaluation and Research is
      responsible for the review of drug and therapeutic biologic applications. The use
      of the word "drugs" in this paper will henceforth refer to both drugs and
      therapeutic biologics (e.g., monoclonal antibodies and small protein molecules).
      Information about vaccines and other biologics, such as antisera and blood
      products, should be obtained from the Center for Biologic Evaluation and
      Research.

PMID- 18323861
TI  - The effect of CYP2C19 polymorphism on the pharmacokinetics and pharmacodynamics
      of clopidogrel: a possible mechanism for clopidogrel resistance.
AB  - We evaluated the effect of the CYP2C19 genotype on the pharmacokinetics and
      pharmacodynamcis of clopidogrel. Twenty-four subjects were divided into three
      groups on the basis of their CYP2C19 genotype: homozygous extensive metabolizers
      (homoEMs, n = 8), heterozygous EMs (heteroEMs, n = 8), and poor metabolizers
      (PMs, n = 8). After a single 300-mg loading dose of clopidogrel on day 1,
      followed by a 75-mg daily maintenance dose from days 2 to 7, we measured the
      plasma levels of clopidogrel and assessed the antiplatelet effect as
      pharmacodynamics. The mean clopidogrel area under the curve (AUC) for PMs was 1.8
      and 2.9-fold higher than that for heteroEMs and homoEMs, respectively (P =
      0.013). The mean peak plasma concentration in PMs was 1.8- and 4.7-fold higher
      than that of heteroEMs and homoEMs, respectively (P = 0.008). PMs exhibited a
      significantly lower antiplatelet effect than heteroEMs or homoEMs (P < 0.001).
      From these findings it is clear that the CYP2C19 genotype affects the plasma
      levels of clopidogrel and modulates the antiplatelet effect of clopidogrel.

PMID- 18323862
TI  - Estrogens and thrombosis.

PMID- 18323863
TI  - Bax siRNA promotes survival of cultured and allografted granule cell precursors
      through blockade of caspase-3 cleavage.
AB  - Transplantation of neuronal precursor cells (NPCs) into the central nervous
      system could represent a powerful therapeutical tool against neurodegenerative
      diseases. Unfortunately, numerous NPCs die shortly after transplantation,
      predominantly due to caspase-dependent apoptosis. Using a culture of cerebellar
      neuronal precursors, we have previously demonstrated protective effect of the
      neuropeptide PACAP, which suppresses ceramide-induced apoptosis by blockade of
      the mitochondrial apoptotic pathway. The main objective of this study was to
      determine whether Bax repression can promote survival of NPCs allotransplanted
      into a host animal. In vivo and ex vivo experiments revealed that C2-ceramide
      increases Bax expression, while PACAP reverses this effect. In vitro tests using
      cerebellar NPCs demonstrated that the Bax-specific small interfering RNA (siRNA)
      could reduce their death and caspase-3 cleavage within the first 24 h. BrdU
      labelled NPCs were subjected to transfection procedure with or without siRNA
      introduction before using for in vivo transplantation. Twenty-four hours after,
      the allografted NPCs containing siRNA showed significantly reduced level of
      caspase-3 cleavage, and the volume of their implants was almost twofold higher
      than in the case of empty-transfected precursors. These data evidence an
      important role of Bax in life/death decision of grafted NPCs and suggest that RNA
      interference strategy may be applicable for maintaining NPCs survival within the
      critical first hours after their transplantation.

PMID- 18323864
TI  - Dry small pleural dissemination of adenocarcinoma of the lung preoperatively
      detected by PET/CT: a report of two cases.
AB  - Dry pleural dissemination in non-small cell lung cancer, defined as solid pleural
      metastasis of lung cancer without pleural effusion, is a condition occurring in
      T4 lung cancer. Positron emission tomography (PET) has been reported to be useful
      for the diagnosis and staging of lung cancer. It has been reported that positive
      findings on PET scans of indeterminate pleural abnormalities at computed
      tomography (CT) are sensitive to malignancy. We encountered two cases of dry
      small pleural dissemination of adenocarcinoma of the lung preoperatively detected
      by PET/CT. A 75-year-old man and a 66-year-old man underwent CT scan, which
      demonstrated solitary tumor in the lung, an enlarged mediastinal lymph node, and
      a small pleural nodule less than 10 mm in size, all of which were positive
      findings on the fluorine 18 fluorodeoxyglucose (FDG) PET portion of an integrated
      PET/CT. Both patients underwent thoracoscopic biopsy of the dry pleural nodule
      revealing dissemination of adenocarcinoma of the lung (T4). Whereas histological
      thoracoscopic diagnosis remains mandatory before planning treatment, our cases
      may suggest that PET/CT will be useful as a screening modality for dry pleural
      dissemination of lung cancer.

PMID- 18323865
TI  - Advances in the molecular biology of malignant mesothelioma.
AB  - Malignant mesothelioma (MM) is a highly aggressive tumor with a dismal prognosis.
      The incidence of MM is increasing as a result of widespread exposure to asbestos.
      As for the molecular alterations that occur in MM, chromosome alterations
      including homo-deletion of the P16 and P14 genes located in the 9p21 are well
      known. Mutations are rare in the P53 and Ras genes, which are frequently present
      in epithelial solid tumors. However, mutations are frequently present in the
      neurofibromatosis type 2 gene. Epigenetic alterations including DNA methylation
      have been found in the MM, the profile of which is different from that of lung
      cancer, although differential diagnosis is sometimes clinically difficult. As in
      other malignant tumors, genes that are related to immortalization, proliferation,
      metastasis, angiogenesis, and anti-apoptosis are also overexpressed in MM,
      contributing to its malignant phenotype. It is of interest that simian virus 40
      has been implicated to be one of the causative factors of MM in western
      countries. Although the causative role of asbestos is well-known in MM, much less
      information is available for MM than for other malignant tumors regarding the
      molecular alterations that occur in the disease. In terms of future tasks, it
      will be necessary to apply the knowledge that is learned about molecular
      alterations to clinical practice and to further elucidate the pathogenesis of MM
      with extensive research.

PMID- 18323866
TI  - Iodine-125 seed implantation (permanent brachytherapy) for clinically localized
      prostate cancer.
AB  - From January 2004 to March 2007, 308 patients with clinically localized prostate
      cancer were treated using iodine-125 (125I) seed implantation (permanent
      brachytherapy) at Okayama University Graduate School of Medicine, Dentistry and
      Pharmaceutical Sciences. We evaluated the treatments efficacy and morbidity in
      300 prostate cancer patients who were followed up for more than 1 month after
      brachytherapy. Based on the National Comprehensive Cancer Network (NCCN)
      guidelines, patients with a prostate volume of less than 40 ml in transrectal
      ultrasound imaging were classified as low or intermediate risk. The median
      patient age was 67 years (range 50 to 79 years), the median prostate-specific
      antigen (PSA) value before biopsy was 6.95 ng/ml (range 1.13 to 24.7 ng/ml), and
      the median prostate volume was 24.33 ml (range 9.3 to 41.76 ml). The median
      follow-up was 18 months (range 1 to 36 months) and the PSA levels decreased in
      almost all patients after brachytherapy. Although 194 of 300 patients (64.7%)
      complained of difficulty in urination, pollakisuria/urgency, miction pain, and/or
      urinary incontinence, all of which might be associated with radiation prostatitis
      during the first month after brachytherapy, these symptoms gradually improved.
      125I seed implantation brachytherapy is safe and effective for localized prostate
      cancer within short-term follow up.

PMID- 18323867
TI  - A prototype model using clinical document architecture (CDA) with a Japanese
      local standard : designing and implementing a referral letter system.
AB  - Since clinical document architecture (CDA) became an American National Standards
      Institute (ANSI)-approved health level seven (HL7) Standard, many countries have
      begun making an effort to make local standards conform to CDA. In order to make
      CDA compatible with the many different local standards existing in different
      countries, we designed a prototype model using HL7 CDA R2 with medical markup
      language (MML), a Japanese medical data exchange standard. Furthermore, a
      referral letter system based on this model was developed. Archetypes were used to
      express medical concepts in a formal manner and to make 2 different standards
      work collaboratively. We share herein the experience gathered in designing and
      implementing a referral letter system based on HL7 CDA, Release 2 (CDA R2). We
      also outline the challenges encountered in our project and the opportunities to
      widen the scope of this approach to other clinical documents.

PMID- 18323868
TI  - Critical differences in magnitude and duration of N-methyl D-aspartate(NMDA)
      receptor activation between long-term potentiation (LTP) and long-term depression
      (LTD) induction.
AB  - The induction of both long-term potentiation (LTP) and long-term depression (LTD)
      in the hippocampal CA1 region is triggered by the activation of N-methyl-D
      aspartate (NMDA) receptors and the subsequent postsynaptic intracellular Ca2+
      increase. However, how NMDA receptor activation differs between LTP and LTD
      induction is unclear. In the present study, we examined the effects of the
      magnitude and duration of NMDA receptor activation on the induction of LTP and
      LTD. Partial blockage of NMDA receptors by a low concentration of
      aminophosphonovaleric acid (APV) (2 microM) prevented the induction of LTP, but
      not LTD. In contrast, a high concentration of APV (25 microM) blocked both LTP
      and LTD. Tetanus stimulation-induced LTP was impaired when hippocampal slices
      were given the tetanus stimulation for more than 5 min. Under partial blockage of
      NMDA receptors, the prolonged-tetanus stimulation induced LTD but not LTP. This
      phenomenon was mimicked by the application of glutamate to the slices. Finally,
      LTD induced by prolonged activation of NMDA receptors was not affected by
      inhibition of the desensitization of alpha-amino-3-hydroxy-5-methylisoxazole-4
      propionic acid (AMPA) receptors. These results suggest that critical differences
      exist between the induction of LTP and that of LTD in terms of both the magnitude
      and the duration of NMDA receptor activation. The duration of the increase in
      intracellular Ca2+ concentration may be critical for determining whether LTP or
      LTD induction occurs.

PMID- 18323869
TI  - Incidence of serious upper gastrointestinal bleeding in patients taking non
      steroidal anti-inflammatory drugs in Japan.
AB  - Upper gastrointestinal bleeding is a major adverse event of non-steroidal anti
      inflammatory drugs (NSAIDs), and co-administration of proton pump inhibitors and
      H2 receptor antagonists has been established as a means of preventing such an
      effect. However, the incidence of bleeding associated with NSAID-induced ulcers
      under conditions where such strong anti-acid agents are used for prevention has
      yet to be clarified. We aimed to determine the annual incidence of serious upper
      gastrointestinal ulcer bleeding among Japanese patients in whom NSAIDs were used
      in our hospital. Before commencing the study, we recommended to all the
      physicians in our hospital the best method for caring for NSAID users, focusing
      on the concomitant use of proton pump inhibitors or H2 receptor antagonists. We
      conducted a cohort study involving 17,270 patients for whom NSAIDs had been newly
      prescribed. Bleeding from gastric ulcers was observed in 8 of the 17,270 patients
      using NSAIDs (0.05%). The pooled incidence rate for bleeding was calculated as
      2.65 (95% confidence interval, 2.56-2.74) and 1.29 (1.27-1.31) per 1,000 patient
      years for low-dose aspirin and non-aspirin NSAID users, respectively. None of the
      bleeding ulcer patients required blood transfusion or were in serious condition.
      In conclusion, gastric ulcer bleeding occurred in low-dose aspirin or non-aspirin
      NSAID users, but its incidence was low and outcomes were not serious when
      adequate preventive measures were taken.

PMID- 18323870
TI  - Phase I trial of escalating-dose cisplatin with 5-fluorouracil and concurrent
      radiotherapy in Chinese patients with esophageal cancer.
AB  - We defined the maximum-tolerated dose (MTD) of chemoradiotherapy (cisplatin
      (CDDP) with 5-fluorouracil (5-FU) and concurrent chemoradiotherapy) for Chinese
      patients with esophageal cancer. Twenty-one previously untreated patients with
      primary esophageal cancer were entered into this study. Escalating doses of CDDP
      with 5-FU were administered in a modified Fibonacci sequence, with concurrent
      conventional fractionation radiotherapy (CFR) of 60 Gy or 50 Gy. The starting
      doses were CDDP 37.5 mg/m2 on day 1, and 5-FU 500 mg/m2 on days 1-5,
      respectively. The regimen was repeated 4 times every 28 days. If no dose-limiting
      toxicity (DLT) was observed, the next dose level was applied. The procedures were
      repeated until DLT appeared. The MTD was declared to be 1 dose level below the
      level at which DLT appeared. DLT was grade 3 radiation-induced esophagitis at a
      dose level of CDDP 60 mg/m2 with 5-FU 700 mg/m2 and concurrent 60 Gy CFR. MTD was
      defined as CDDP 52.5 mg/m2 with 5-FU 700 mg/m2 and concurrent 50 Gy CFR. The MTD
      of CDDP with 5-FU and in concurrent chemoradiotherapy for Chinese patients with
      esophageal cancer is CDDP 52.5 mg/m2 on day 1 and 5FU 700 mg/m2 on days 1-5,
      repeated 4 times every 28 days, and concurrent 50 Gy CFR. Further evaluation of
      this regimen in a prospective phase II trial is ongoing.

PMID- 18323871
TI  - Clinical features, ARIX and PHOX2B nucleotide changes in three families with
      congenital superior oblique muscle palsy.
AB  - We analyzed nucleotide changes in 3 genes, ARIX, PHOX2B, and KIF21A, in 6
      patients of 3 families with congenital superior oblique muscle palsy. Three exons
      of ARIX, 3 exons of PHOX2B, and exons 8, 20, and 21 of KIF21A were amplified by
      polymerase chain reaction from genomic DNA isolated from the peripheral blood.
      The DNA fragments were directly sequenced in both directions. In 2 different
      families, a heterozygous nucleotide change, ARIX 153G>A, in the 5'.-untranslated
      region was found in common between a father and daughter with muscle palsy and
      between a mother and daughter with muscle palsy (Family No. 1 and No. 3). In the
      other family (Family No. 2), a heterozygous 15-nucleotide deletion, PHOX2B
      1124del15, resulting in loss of 5 alanine residues in the alanine repeat of the
      protein, was found in the daughter with muscle palsy and her father with normal
      traits, but was not found in the mother with muscle palsy. No KIF21A nucleotide
      change was found in any patients. The ARIX 153G>A polymorphism might be a genetic
      risk factor for the development of congenital superior oblique muscle palsy.

PMID- 18323872
TI  - Dental implant treatment for a patient with bilateral cleft lip and palate.
AB  - Dental reconstruction in the cleft space is difficult in some patients with cleft
      lip and palate because of oronasal fistulas. Most of these patients receive a
      particle cancellous bone marrow (PCBM) graft to close the alveolar cleft, and
      secondary bone grafting is also required. Treatment options for the alveolar
      cleft including fixed or removable prostheses require the preparation of healthy
      teeth and are associated with functional or social difficulties. Recently, the
      effectiveness of dental implant treatment for cleft lip and palate patients has
      been reported. However, there have been few reports on the use of this treatment
      in bilateral cleft lip and palate patients. We report the case of a patient who
      had bilateral cleft lip and palate and was missing both lateral incisors. She
      received dental implant treatment after a PCBM graft and ramus bone onlay
      grafting (RBOG). A 34-month postoperative course was uneventful.

PMID- 18323873
TI  - Method of random wave vectors in simulation of anisoplanatic effects.
AB  - A generalization of the method of random wave vectors [Appl. Opt. 36, 464 (1997)]
      that is suitable for a simulation of turbulence-induced anisoplanatic effects is
      proposed. A simulation of the cross-correlated phase fluctuations produced by two
      initially plane waves propagating through weak turbulence is considered. The
      variation of C(n)(2) along a propagation path and an effect of the finite outer
      scale of the turbulence are included in the simulation. The validity of the
      simulation method is verified by comparison of theoretical and simulated results.
      The simulation approach developed can be used in the problems related to adaptive
      optics, speckle inteferometry, guide stars, and imaging through turbulence.

PMID- 18323874
TI  - Deconvolution method for two-dimensional spatial-response mapping of lithographic
      infrared antennas.
AB  - The spatial impulse response of antenna-coupled infrared detectors with
      dimensions comparable with the wavelength is obtained from a two-dimensional scan
      of a tightly focused CO(2)-laser beam. The method uses an experimental setup with
      submicrometer resolution and an iterative deconvolution algorithm. The measured
      spatial response is compared with numerically computed near-field distributions
      of a dipole antenna, with good agreement.

PMID- 18323875
TI  - Comparison of mechanically ruled versus holographically varied line-spacing
      gratings for a soft-x-ray flat-field spectrograph.
AB  - Recent progress in the design of aspheric wave-front recording systems has
      permitted the manufacture of holographic gratings with highly variable groove
      densities that are suitable for flat-field spectrographs. A holographic grating
      thus recorded was processed to produce a laminar profile by use of reactive-ion
      etching. Measurements are reported of the absolute diffraction efficiency of this
      grating and of a comparable mechanically ruled grating. It is found that the
      holographic grating is much more effective in suppressing the higher orders. The
      spectral resolution was determined by use of a carbon Kalpha x-ray generator and
      a spectrograph with an imaging detector. The spectral resolution of the
      holographic grating was approximately 3 times worse than that of the ruled
      grating.

PMID- 18323876
TI  - Characteristics of ray traces at the back of biaxial crystals at normal
      incidence.
AB  - Ray vector traces that can be obtained at the back of a biaxial crystal through
      crystal rotation are calculated numerically by variation of one of the three
      Euler angles. Negative and positive lossless biaxial crystals are considered at
      normal incidence. Interesting features of these traces are evidenced by reference
      to the circular ring that forms at internal conical refraction.

PMID- 18323877
TI  - Field improvement in a uniaxial centered lens composed of two stacked-volume
      holographic elements.
AB  - Arrangements are described for the recording of volume holograms with two
      sections that, when stacked together, work as uniaxial centered lenses and allow
      one to solve the problem of angular selectivity in the imaging of wide objects.
      The performance of such systems is examined qualitatively, and suggestions aimed
      at improving these designs are proposed.

PMID- 18323878
TI  - Intensity-modulated moire topography.
AB  - Moire topography has the advantage of requiring only a single image to obtain a
      three-dimensional measurement, but it cannot discern the fringe order. Because
      there is an ambiguity problem when calculating the depth range by use of fringe
      intensity or phase unwrapping, it is impossible to obtain an absolute phase and
      an absolute depth range. It is therefore difficult to discern the relation
      between fringes in the cases in which the fringes are discontinuous or the
      objects are isolated. An intensity-modulated moire topography method is
      presented. By modulation of the transmission factors of the projection and the
      observation gratings by exponential functions a new moire pattern whose fringe
      intensity changes with its order can be produced. The fringe order can be
      extracted easily from the fringe intensity, and the absolute range of the
      skeleton line can be obtained solely from its intensity. At the same time, we can
      segment the moire pattern by its fringe order. For every segment the absolute
      phase and the absolute depth range of every point of the moire pattern can be
      obtained solely from its intensity with no need for interaction with the user.

PMID- 18323879
TI  - Application of digital speckle photography to flash X-ray studies of internal
      deformation fields in impact experiments.
AB  - A technique to measure two-dimensional deformation fields of a layer inside
      materials during dynamic events such as impact experiments is presented. Even
      optically opaque materials like cement can be evaluated when flash x rays are
      used. Blocks of polyester and cement were prepared with a layer of x-ray
      absorbing lead particles. The specimens were then hit by a 9-mm-diameter steel
      sphere (ball bearing) fired from a 9-mm-bore gas gun at a velocity of 373.5 +/-
      3.0 ms(-1). A 30-ns-long x-ray pulse exposed one radiograph before impact;
      another radiograph was exposed a short time after the impact on the specimen. The
      two-dimensional displacement field was obtained when the x-ray radiographs were
      digitized by a conventional flatbed scanner, and a digital speckle photography
      algorithm was used to calculate the displacements. The flash x-ray technique
      allowed examination of the deformation at the layer inside the material during
      failure, thus giving interesting data about the material flow field around the
      impactor.

PMID- 18323880
TI  - Simulation study on refractometry by the rainbow method.
AB  - To realize a high-precision refractive-index measurement by the rainbow method by
      use of multifringes, the characteristics of several orders of supernumerary bow
      fringes are made clear by a simulation based on the Huygens-Fresnel principle.
      The fringe intervals computed are precisely coincident with those obtained in
      experiments. As a result a suitable combination of the diameter of the cylinder
      containing the sample and the beam size of the laser has been determined. By use
      of the characteristic curve of the deviation angle versus the refractive index
      for each fringe and by the statistical treatment, measurement with high precision
      was demonstrated.

PMID- 18323881
TI  - Complex refractive-index measurement based on Fresnel's equations and the uses of
      heterodyne interferometry.
AB  - The phase difference between s and p polarization of the light reflected from a
      material is used for measuring the material's complex refractive index. First,
      two phase differences that correspond to two different incidence angles are
      measured by heterodyne interferometry. Then these two phase differences are
      substituted into Fresnel's equations, and a set of simultaneous equations is
      obtained. Finally, the equations are solved by use of a personal computer by a
      numerical analysis technique, and the complex refractive index of the material
      can be estimated.

PMID- 18323882
TI  - Water at the ice point: a useful quasi-blackbody infrared calibration source.
AB  - Water at the ice point makes a good calibration source in the 4- to 13-microm
      spectral region because of its high emissivity, small skin depth, and the ease
      with which an ice-point bath may be prepared and used. In a simple ice bath the
      emissivity is slightly less than unity, and we have calculated corrections that
      allow one to predict the apparent radiation temperature of the equivalent
      blackbody. We propose an alternate configuration that uses an auxiliary mirror.
      This configuration should provide an emissivity extremely close to unity.

PMID- 18323883
TI  - Refractive-index and thickness sensitivity in surface plasmon resonance
      spectroscopy.
AB  - The sensitivities of surface plasmon resonance spectroscopy were examined at
      incident angles of 66-76 deg. The sensitivities were calculated for various
      refractive indices of liquid samples and for various thicknesses of deposited
      dielectric thin layers. Furthermore, the sensitivities were confirmed
      experimentally. The experimentally measured refractive indices and thicknesses
      were 1.3311-1.3463 and 0-89 nm, respectively. From these results it was
      demonstrated that the sensing system showed higher sensitivities with smaller
      incident angles. For example, the sensitivity for a refractive index at a 66
      degrees incident angle was seven times larger than that at 76 degrees. It was
      also demonstrated that the resonant wavelength has a linear relation to the
      refractive index and the thickness at refractive indices and thicknesses of 1.33
      1.345 and 0-100 nm, respectively, except for a 66 degrees incident angle.

PMID- 18323884
TI  - Separation of measurement of the refractive index and the geometrical thickness
      by use of a wavelength-scanning interferometer with a confocal microscope.
AB  - An improved system for the separate measurement of the refractive index and the
      geometrical thickness that constitutes a hybrid configuration of a confocal
      microscope and a wavelength-scanning heterodyne interferometer with a laser diode
      is presented. The optical path difference can be measured in less than 1 s, which
      is 10 times quicker than with the low-coherence interferometry previously used,
      and with a resolution of 10 microm with a fixed reference mirror. Separate
      measurement of the refractive index and the geometrical thickness of glass plates
      was demonstrated by use of the arrangement in place of the low-coherence
      interferometer used previously.

PMID- 18323885
TI  - Soft-x-ray polarimeter with multilayer optics: complete analysis of the
      polarization state of light.
AB  - The design of a versatile high-precision eight-axis ultrahigh-vacuum-compatible
      polarimeter is presented. This multipurpose instrument can be used as a self
      calibrating polarization detector for linearly and circularly polarized UV and
      soft-x-ray light. It can also be used for the characterization of reflection or
      transmission properties (reflectometer) or polarizing and phase-retarding
      properties (ellipsometer) of any optical element. The polarization properties of
      Mo/Si, Cr/C, Cr/Sc, and Ni/Ti multilayers used in this polarimeter as polarizers
      in transmission and as analyzers in reflection have been investigated
      theoretically and experimentally. In the soft-x-ray range, close to the p edges
      of Sc, Ti, and Cr, resonantly enhanced phase retardation of the transmission
      polarizers of as much as 18 degrees has been measured. With these newly developed
      optical elements the complete polarization analysis of soft-x-ray synchrotron
      radiation can be extended to the water-window range from 300 to 600 eV.

PMID- 18323886
TI  - Heterodyne interferometer with subatomic periodic nonlinearity.
AB  - A new, to our knowledge, heterodyne interferometer for differential displacement
      measurements is presented. It is, in principle, free of periodic nonlinearity. A
      pair of spatially separated light beams with different frequencies is produced by
      two acousto-optic modulators, avoiding the main source of periodic nonlinearity
      in traditional heterodyne interferometers that are based on a Zeeman split laser.
      In addition, laser beams of the same frequency are used in the measurement and
      the reference arms, giving the interferometer theoretically perfect immunity from
      common-mode displacement. We experimentally demonstrated a residual level of
      periodic nonlinearity of less than 20 pm in amplitude. The remaining periodic
      error is attributed to unbalanced ghost reflections that drift slowly with time.

PMID- 18323888
TI  - Measurement of phase objects by simple means.
AB  - A printed fringe pattern is imaged by a CCD camera, whereas a phase object is
      placed in the ray path for imaging. The ray deflections distort the image of the
      pattern and are measured by evaluation of the image with the Fourier transform
      method.

PMID- 18323887
TI  - Comparison of fourier-transform and data-dependent system profilometry by use of
      interferometric regeneration.
AB  - Fourier-transform profilometry (FTP) and data-dependent system profilometry
      (DDSP) are the two major phase-extraction methods that use a single
      interferogram. The difficulty in verifying surface profiles obtained by these
      methods is that the exact spot on an actual surface cannot be measured with two
      different instruments. An interferogram regeneration procedure is developed to
      solve this problem. The surface profile is then extracted from the regenerated
      interferogram by both FTP and DDSP. Comparisons of the actual surface profile
      with the extracted surface profiles show that both methods perform equally well
      in measuring the root mean square and the center line average, but only DDSP is
      able to reproduce the detailed surface profile of the reference surface.

PMID- 18323889
TI  - Multifrequency grating projection profilometry based on the nonlinear excess
      fraction method.
AB  - Although promised to be a fast and accurate three-dimensional shape measurement
      technique, grating projection profilometry based on phase measurement has been
      frequently baffled by the difficulty in phase unwrapping. We introduce the
      conventional excess fraction method into profilometry and extend it to nonlinear
      domain. Nonlinear excess fraction method (NLEFM), on the basis of which a
      multifrequency grating projection profilometry is developed, can work as a robust
      temporal phase unwrapper, which may extend the reliable measuring range by dozens
      of times at no cost of accuracy. The principle of NLEFM is detailed, and
      experimental results are given in which complex profiles are reliably measured
      with the novel system.

PMID- 18323890
TI  - Effects of unparallel grating planes in Talbot interferometry.
AB  - The properties of moire fringes in Talbot interferometry are analyzed when the
      angle between the two grating planes is small. The results indicate that the tilt
      angle of the moire fringes, observed just behind the test grating, is sensitive
      to the small angle. Based on this sensitivity, several features of parallelism of
      the two grating planes are presented, and the influence of the small angle when
      checking the beam collimation of a lens is also discussed. The validity of the
      theoretical analysis is illustrated by experiment.

PMID- 18323891
TI  - Microlens formation by thin-film deposition with mesh-shaped masks.
AB  - Thin-film microlens arrays with high fill factors have been fabricated in a one
      step process by shading a vapor beam in a vacuum-deposition apparatus with
      metallic meshes placed at defined distances to the substrate surface. To generate
      three-dimensional mask structures with the necessary depth profiles,
      microgalvanic technology has been applied. Profiles and optical properties of the
      microlenses have been studied theoretically and experimentally.

PMID- 18323892
TI  - Optical characterization of a compact multilayer-mirror polarimeter in the
      extreme-ultraviolet range.
AB  - A molybdenum-silicon (Mo/Si) multilayer-mirror (MLM) polarimeter has been
      constructed and used to analyze the extreme-ultraviolet (EUV) emission from
      excited HeI and HeII states following electron impact on He for wavelengths
      ranging from approximately 256 to 584 A. A ratio of reflectivities for s- and p
      polarized light, R(s):R(p) approximately , and a resolving power of
      lambda/Dlambda approximately 6 at 304 A were obtained. These characteristics and
      the use of a VYNS (a copolymer material composed of 90% vinyl chloride and 10%
      vinyl acetate) spectral filter were sufficient to allow a detailed polarization
      study of the first two members of the Lyman series of He(+) at wavelengths of 304
      A (HeII p --> s) and 256 A (HeII p --> s) for impact-electron energies ranging
      from threshold to 1500 eV. The MLM has also been used as a single flat-surface
      mirror polarimeter for the analysis of longer-wavelength radiation (517 to 584 A)
      from the (snp) (1) P (o) --> (1s(2)) (1) S series of neutral He with R(s)/R(p)
      approximately. Although MLM polarimeters were previously used for EUV
      measurements with bright photon sources such as those provided by synchrotron
      facilities, the results presented clearly demonstrate the feasibility of such
      devices with lower-intensity electron and ion impact sources. The compact design
      of the apparatus makes it suitable as a portable measurement and calibration
      device.

PMID- 18323893
TI  - Optical properties of a retroreflecting sheet.
AB  - The power reflection and polarization properties of a close-packed array of
      retroreflectors are modeled, and a commercially available sheet is measured to
      verify the predictions. The modeling technique is conceptually simple and
      applicable to a wide range of structures of this type. The close-packed sheet
      retroreflects over a range of angles of incidence of approximately -40 to 40 deg
      in both directions and returns the polarization that illuminates it largely
      unchanged. Predictions of returned power are within 10% for light incident within
      15 deg of normal and within 20% for angles less than 20 deg. Angles of
      polarization rotation are predicted to within 10 deg over a similar range of
      input angles. The model predicts the angular aperture of the sheet and the major
      features of the angular response. Future research will focus on design of
      structures with wider angles of acceptance and responses optimized for specific
      applications.

PMID- 18323894
TI  - Multiple-pass cell for very-long-path infrared spectrometry.
AB  - A multiple-pass cell for mid-IR spectrometry that has been designed to operate in
      an evacuable environmental chamber is described. Using this new modified White
      arrangement, we can significantly increase the path length while keeping the
      spectrometric beam stable. An approximate expression that ties the number of
      reflections to the optimal signal-to-noise ratio in multiple-reflection cells is
      derived.

PMID- 18323895
TI  - Light-scattering microscope.
AB  - We demonstrate a new design for a light-scattering microscope that is convenient
      to use and that allows simultaneous imaging and light scattering. The design is
      motivated by the growing use of thermal fluctuations to probe the viscoelastic
      properties of complex inhomogeneous environments. We demonstrate measurements of
      an optically nonergodic sample, one of the most challenging light-scattering
      applications.

PMID- 18323896
TI  - Small-angle light scattering: instrumental design and application to particle
      sizing.
AB  - A small-angle integrated light-scattering (SAILS) instrument was designed with
      the innovative use of a diffusing plate and a charge-coupled device (CCD) camera.
      In contrast to previous small-angle light-scattering instruments, SAILS has few
      optical surfaces, allowing the direct recovery of scattering data. Although this
      approach bypasses the need for aberration corrections that are due to lenses,
      geometric corrections still apply and are described in detail. The image on the
      diffusing plate, when photographed by the CCD camera, yields a digitized two
      dimensional array, covering the observed scattering angles from 10 to 20 deg. The
      size distribution of the scattering particles can be obtained by a discrete
      inversion of the experimentally obtained intensity versus angle-scattering curve.
      The mean radii obtained from this inversion of SAILS data are compared with
      nominal sizes given by the manufacturer, and standard errors are computed. The
      results indicate that SAILS is an ideal instrument for the study of particulates
      and, because of its fast readout time, is suitable for studying aggregation
      phenomena. However, because of the limited Q range of SAILS it is currently not
      suited for the direct determination of particle diameters smaller than
      approximately 300 nm.

PMID- 18323897
TI  - Shadow-angle method for anisotropic and weakly absorbing films.
AB  - A method for determining the optical properties of a film on an isotropic
      substrate is proposed. The method is based on the existence of two specific
      incidence angles in the angular interference pattern of the p-polarized light
      where oscillations of the reflection coefficient cease. The first of these
      angles, theta(B1), is the well-known Abeles angle, i.e., the ambient-film
      Brewster angle, and the second angle theta(B2) is the film-substrate Brewster
      angle. In the conventional planar geometry and in a vacuum ambient there is a
      rigorous constraint epsilon(1) + epsilon > epsilon(1)epsilon on the film and the
      substrate dielectric permittivities epsilon(1) and epsilon, respectively, for the
      existence of the second angle theta(B2.) The limitation may be removed in an
      experiment by use of a cylindrical lens as an ambient with epsilon(0) > 1, so
      that both angles become observable. This, contrary to general belief, allows one
      to adopt the conventional Abeles method not only for films with epsilon(1) close
      to the substrate's value epsilon but also for any value of epsilon(1). The
      method, when applied to a wedge-shaped film or to any film of unknown variable
      thickness, permits one to determine (i) the refractive index of a film on an
      unknown substrate, (ii) the vertical and the horizontal optical anisotropies of a
      film on an isotropic substrate, (iii) the weak absorption of a moderately thick
      film on a transparent or an absorbing isotropic substrate.

PMID- 18323898
TI  - Anisotropic protective coating for brewster angle windows.
AB  - We propose what we believe is a new type of dielectric anisotropic coating of
      arbitrary thickness that can protect Brewster angle windows without degrading
      their optical quality. Such a coating may be fabricated as a multilayer two
      component structure. The parameters of the structure, i.e., the dielectric
      permittivities of the components and their concentrations, are calculated. For
      ZnSe windows two examples of anisotropic coatings are presented. The optical
      quality of the multilayer films does not depend on their precise thickness, which
      makes them less sensitive to surface damage.

PMID- 18323899
TI  - Determination of the refractive indices of layers in a multilayer stack by a
      guided-wave technique.
AB  - The m-lines technique is used to measure the refractive indices and thicknesses
      of layers embedded in a multilayer stack. The multilayer considered is deposited
      by ion plating. Its formula is silica-H-L-H-L-H-air, where H and L denote
      Ta(2)O(5) and SiO(2)lambda/4 layers, respectively, with lambda = 514.5 nm.
      Measurements indicate that the refractive index of Ta(2)O(5) is 5 x 10(-3)
      greater when the layer is close to air than when the layer is inside the coating
      and that the Ta(2)O(5) is slightly more birefringent.

PMID- 18323900
TI  - Infrared optical filters for the infrared atmospheric sounding interferometer
      meteorological space instrument.
AB  - Optical coatings are designed and produced for the Infrared Atmospheric Sounding
      Interferometer meteorological space instrument operating in the spectral range
      3.5 15.5 m. First we discuss the choice of substrates and determine the complex
      refractive indices of thin-film materials. Then several theoretical solutions are
      studied for optimizing the efficiency of the instrument. To allow us to study the
      feasibility of the coatings, a specific mid-infrared optical monitoring system
      has been developed. This system is validated by the successful manufacture of two
      cavity Fabry Perot filters.

PMID- 18323901
TI  - Angular solar absorptance of absorbers used in solar thermal collectors.
AB  - The optical characterization of solar absorbers for thermal solar collectors is
      usually performed by measurement of the spectral reflectance at near-normal angle
      of incidence and calculation of the solar absorptance from the measured
      reflectance. The solar absorptance is, however, a function of the angle of
      incidence of the light impinging on the absorber. The total reflectance of two
      types of commercial solar-selective absorbers, nickel-pigmented anodized
      aluminum, and sputtered nickel nickel oxide coated aluminum are measured at
      angles of incidence from 5 to 80 in the wavelength range 300-2500 nm by use of an
      integrating sphere. From these measurements the angular integrated solar
      absorptance is determined. Experimental data are compared with theoretical
      calculations, and it is found that optical thin-film interference effects can
      explain the significant difference in solar absorptance at higher angles for the
      two types of absorbers.

PMID- 18323902
TI  - Eyeglass. 1. Very large aperture diffractive telescopes.
AB  - The Eyeglass is a very large aperture (25-100-m) space telescope consisting of
      two distinct spacecraft, separated in space by several kilometers. A diffractive
      lens provides the telescope s large aperture, and a separate, much smaller, space
      telescope serves as its mobile eyepiece. Use of a transmissive diffractive lens
      solves two basic problems associated with very large aperture space telescopes;
      it is inherently launchable (lightweight, packagable, and deployable) it and
      virtually eliminates the traditional, very tight surface shape tolerances faced
      by reflecting apertures. The potential drawback to use of a diffractive primary
      (very narrow spectral bandwidth) is eliminated by corrective optics in the
      telescope s eyepiece; the Eyeglass can provide diffraction-limited imaging with
      either single-band (Deltalambda/lambda approximately 0.1), multiband, or
      continuous spectral coverage.

PMID- 18323903
TI  - Nanometer-level path-length control scheme for nulling interferometry.
AB  - A method of stabilizing a dual-output rotational shearing inteferometer to the
      nanometer-level accuracy required for deep starlight nulling in planet searches
      is presented. In this approach one of the nulling beam combiner s two balanced
      outputs is used to control the other through a combination of external and
      internal path-length offsets. The path-length offsets sum to zero for the nulling
      output and to lambda/4 for the control, or the quadrature, output. In the
      quadrature output a 1-nm path-length error corresponds to a 1% output-power
      variation, thus allowing subnanometer control.

PMID- 18323904
TI  - Integrating the digitized backscattered image to measure absorption and reduced
      scattering coefficients in vivo.
AB  - Measurement of absorption and reduced-scattering optical coefficients microa and
      micros' is possible when a steady-state backscattered image is used on a sample
      surface. A new method for processing the backscattered image, acquired with a
      CCD, has been developed. The image is integrated to decrease sensitivity to
      noise. The resulting curve is defined as the integral reflectance. The curve is
      then fitted with a relaxation model to evaluate microa and micros'. We have
      validated the method with calibrated scattering and absorption phantoms. The
      integral reflectance method is then applied to measurements of the microa and
      micros' coefficients of human skin in vivo.

PMID- 18323905
TI  - Experimental tests of different solutions to the diffusion equation for optical
      characterization of scattering media by time-resolved transmittance.
AB  - A detailed investigation of the use of time-resolved trasmittance for the optical
      characterization of scattering media by use of different analytical solutions to
      the diffusion equation has been performed. A femtosecond Ti:sapphire laser
      working at 800 nm and a streak camera with a time resolution of a few picoseconds
      were employed. Different latex and Intralipid solutions as well as biological
      samples were investigated. Reduced scattering coefficients were evaluated, and
      good agreement with the Mie predictions was found. An estimation of the order of
      magnitude of the absorption coefficient was obtained for the low-absorbance
      samples examined. These studies confirm experimentally that time-resolved
      trasmittance can be employed usefully for evaluating s values of thick scattering
      samples when a proper theoretical description that takes into account realistic
      boundary conditions is used.

PMID- 18323906
TI  - Optical tomographic image reconstruction from ultrafast time-sliced transmission
      measurements.
AB  - Optical imaging and localization of objects inside a highly scattering medium,
      such as a tumor in the breast, is a challenging problem with many practical
      applications. Conventional imaging methods generally provide only two-dimensional
      (2-D) images of limited spatial resolution with little diagnostic ability. Here
      we present an inversion algorithm that uses time-resolved transillumination
      measurements in the form of a sequence of picosecond-duration intensity patterns
      of transmitted ultrashort light pulses to reconstruct three-dimensional (3-D)
      images of an absorbing object located inside a slab of a highly scattering
      medium. The experimental arrangement used a 3-mm-diameter collimated beam of 800
      nm, 150-fs, 1-kHz repetition rate light pulses from a Ti:sapphire laser and
      amplifier system to illuminate one side of the slab sample. An ultrafast gated
      intensified camera system that provides a minimum FWHM gate width of 80 ps
      recorded the 2-D intensity patterns of the light transmitted through the opposite
      side of the slab. The gate position was varied in steps of 100 ps over a 5-ns
      range to obtain a sequence of 2-D transmitted light intensity patterns of both
      less-scattered and multiple-scattered light for image reconstruction. The
      inversion algorithm is based on the diffusion approximation of the radiative
      transfer theory for photon transport in a turbid medium. It uses a Green s
      function perturbative approach under the Rytov approximation and combines a 2-D
      matrix inversion with a one-dimensional Fourier-transform inversion to achieve
      speedy 3-D image reconstruction. In addition to the lateral position, the method
      provides information about the axial position of the object as well, whereas the
      2-D reconstruction methods yield only lateral position.

PMID- 18323907
TI  - Fabrication and characterization of a solid polyurethane phantom for optical
      imaging through scattering media.
AB  - A phantom based on a polyurethane system that replicates the optical properties
      of tissue for use in near-infrared imaging is described. The absorption
      properties of tissue are simulated by a dye that absorbs in the near infrared,
      and the scattering properties are simulated by TiO2 particles. The scattering and
      absorption coefficients of the plastic were measured with a new technique based
      on time-resolved transmission through two slabs of materials that have different
      thicknesses. An image of a representative phantom was obtained from time-gated
      transmission.

PMID- 18323908
TI  - Polarization discrimination of coherently propagating light in turbid media.
AB  - We describe the use of degree of polarization to discriminate unscattered and
      weakly scattered light from multiply scattered light in an optically turbid
      material. We use spatially resolved measurements of the degree of polarization to
      compare how well linearly and circularly polarized light survives in a sample.
      Experiments were performed on common tissue phantoms consisting of polystyrene
      and Intralipid microsphere suspensions and on adipose and arterial tissue. The
      results indicate that polarization is maintained even after unpolarized
      irradiance through each sample has been extinguished by several orders of
      magnitude. The results also show that polarized light propagation in common
      tissue phantoms is distinctly different from polarized light propagation in the
      two tissues investigated. Further, these experiments illustrate when polarization
      is an effective discrimination criterion and when it is not. The potential of a
      polarization-based discrimination scheme to image through the biological and
      nonbiological samples investigated here is also discussed.

PMID- 18323909
TI  - Compensated transillumination.
AB  - We demonstrate imaging through human tissue in vivo , using a new optical
      technique, compensated transillumination. Immersion in a scattering medium with
      absorption and scattering coefficients matched to the tissue is used for drastic
      improvement of image contrast. The immersion medium is composed of polymer
      microspheres and methylene blue dye. The optical properties of the medium are
      matched to those of the tissue by use of a frequency-domain measurement
      technique. Images of a human hand taken with this technique show the internal
      structure, including the outlines of bones. The mechanism for the contrast is
      likely the absence of blood between the bones.

PMID- 18323912
TI  - Synthesis of hybrid spatial coherence.
AB  - Spatial coherence plays a major role in characterizing quasi-monochromatic,
      partially coherent, optical signals. Here a fairly simple system for synthesizing
      special cases of spatial coherence is proposed. The special cases, called hybrid,
      include the case of total coherence in the x direction and, simultaneously, total
      incoherence in the y direction. The optical setup is based on a quasi
      monochromatic, spatially coherent light source, such as a laser, and a simple
      moving optical element.

PMID- 18323913
TI  - Genetic local search algorithm for optimization design of diffractive optical
      elements.
AB  - We propose a genetic local search algorithm (GLSA) for the optimization design of
      diffractive optical elements (DOE's). This hybrid algorithm incorporates
      advantages of both genetic algorithm (GA) and local search techniques. It appears
      better able to locate the global minimum compared with a canonical GA. Sample
      cases investigated here include the optimization design of binary-phase Dammann
      gratings, continuous surface-relief grating array generators, and a uniform top
      hat focal plane intensity profile generator. Two GLSA's whose incorporated local
      search techniques are the hill-climbing method and the simulated annealing
      algorithm are investigated. Numerical experimental results demonstrate that the
      proposed algorithm is highly efficient and robust. DOE's that have high
      diffraction efficiency and excellent uniformity can be achieved by use of the
      algorithm we propose.

PMID- 18323914
TI  - Secondary grating formation by readout at Bragg-null incidence.
AB  - We show that when a dynamic hologram is read out by illumination at the Bragg
      nulls of a previously recorded grating the diffracted beam inside the medium can
      result in the recording of two secondary gratings that alter the final
      selectivity curve. This is confirmed experimentally. This effect can cause cross
      talk in hologram multiplexing that is stronger than interpage cross talk when a
      small number of holograms with high diffraction efficiencies are multiplexed.

PMID- 18323915
TI  - Filter implementation technique for multicriteria characterization of coding
      domains in the joint transform correlator.
AB  - An improved method for implementing correlation filters in the joint transform
      correlator architecture is proposed. We derived the method from computer
      generated holography techniques. It allows us to use any correlation filters,
      especially ones that provide an optimal trade-off between noise robustness, peak
      sharpness, and optical efficiency, with any spatial light modulator (SLM). This
      method also allows for an objective comparison of the performance of the coding
      domains of various SLM's.

PMID- 18323916
TI  - Optical Fourier processor and point-diffraction interferometer for moving-object
      trajectory estimation.
AB  - A hybrid optical-digital signal processing system that estimates the trajectory
      of moving targets in a two-dimensional field at video frame rates was developed
      and constructed. The hybrid system is particularly well suited to the trajectory
      estimation of small, barely discernable, moving objects of unknown position and
      velocity in high-resolution image sequences. The system uses an optical Fourier
      processor and a point-diffraction interferometer to calculate the frequency
      domain representation of moving objects from which their trajectory is estimated
      by use of conventional electronic processing techniques. In a series of
      experiments, target velocities were estimated to within 4% of their actual value
      and direction was estimated to within 3 deg.

PMID- 18323917
TI  - Two-dimensional shifting tolerance of a volume-holographic correlator.
AB  - A simple method for simulating two-dimensional (2-D) distributions of the
      diffraction lights of a volume-holographic-type VanderLugt correlator is proposed
      and demonstrated. The simulation results are similar to those of the
      corresponding experiments, and only a few dozen points are sampled from both the
      input and the reading patterns. We show that the shifting tolerance to the
      reading pattern is a result of Bragg degeneracy and is not isotropic. The Bragg
      degeneracy generates different degrees of cross talk between the horizontal and
      the vertical directions. With the method we further simulate the 2-D shifting
      tolerance of the volume-holographic correlator. The simulation results offer a
      clear picture of the diffraction in a transmission volume hologram used as an
      optical spatial correlator.

PMID- 18323918
TI  - Comparison of direct blind deconvolution methods for motion-blurred images.
AB  - Direct methods for restoration of images blurred by motion are analyzed and
      compared. The term direct means that the considered methods are performed in a
      one-step fashion without any iterative technique. The blurring point-spread
      function is assumed to be unknown, and therefore the image restoration process is
      called blind deconvolution. What is believed to be a new direct method, here
      called the whitening method, was recently developed. This method and other
      existing direct methods such as the homomorphic and the cepstral techniques are
      studied and compared for a variety of motion types. Various criteria such as
      quality of restoration, sensitivity to noise, and computation requirements are
      considered. It appears that the recently developed method shows some improvements
      over other older methods. The research presented here clarifies the differences
      among the direct methods and offers an experimental basis for choosing which
      blind deconvolution method to use. In addition, some improvements on the methods
      are suggested.

PMID- 18323919
TI  - Performance evaluation of two-dimensional phase unwrapping algorithms.
AB  - We present a performance evaluation of eight two-dimensional phase unwrapping
      methods with respect to correct phase unwrapping and execution times. The
      evaluated methods are block least squares (BLS), adaptive integration (AI),
      quality guided path following (QUAL), mask cut (MCUT), multigrid (MGRID),
      preconditioned conjugate gradient (PCG), Flynn's (FLYNN), and Liang's (LIANG).
      This set included integration- (path following), least-squares-, L(1)-, and model
      based methods. The methods were tested on several synthetic images, on two
      magnetic resonance images, and on two interferometry images. The synthetic images
      were designed to demonstrate different aspects of the phase unwrapping problem.
      To test the noise robustness of the methods, independent noise was added to the
      synthetic images to yield different signal-to-noise ratios. Each experiment was
      performed 50 times with different noise realizations to test the stability of the
      methods. The results of the experiments showed that the congruent minimum L(1)
      norm FLYNN method was best overall and the most noise robust of the methods, but
      it was also one of the slowest methods. The integration-based QUAL method was the
      only method that correctly unwrapped the two interferometry images. The least
      squares-based methods (MGRID, PCG) gave worse results on average than did the
      integration- (or path following) based methods (BLS, AI, QUAL, MCUT) and were
      also slower. The model-based LIANG method was sensitive to noise and resulted in
      large errors for the magnetic resonance images and the interferometry images. In
      conclusion, for a particular application there is a trade-off between the quality
      of the unwrapping and the execution time when we attempt to select the most
      appropriate method.

PMID- 18323920
TI  - Parallel-distributed blind deconvolution based on a self-organizing neural
      network.
AB  - A parallel-distributed blind deconvolution method based on a self-organizing
      neural network is introduced. A large degraded image is segmented into smaller
      subpatterns. Each subpattern can be used to get a blur function. Moreover, we
      propose a two-step unsupervised learning method in the self-organizing neural
      network. The two-step learning method includes parallel learning and series
      learning operations. The series learning operation is similar to a typical
      learning operation in the self-organizing neural network. The parallel learning
      operation is used as a positive perturbation to let the learning operation leave
      a local minimum. Several improved blur functions can be estimated from the
      different subpatterns, and the optimized blur function is evolved by use of a
      genetic algorithm. As the blur function is estimated, the source image of the
      large degraded image can be easily restored by use of a Wiener-type filter or
      other deconvolution methods. Computer simulations show that the proposed parallel
      distributed blind deconvolution method gives good reconstruction and that the two
      step learning method in the self-organizing neural network can promote learning.
      Since the main computational cost is dependent on the size of the subpattern, the
      proposed method is effective for the restoration of the large image.

PMID- 18323921
TI  - Optical implementation of fuzzy-logic controllers. Part II.
AB  - In part I of a previous study [Appl. Opt. 37, 6937 (1998)] we introduced what is
      believed to be a novel two-dimensional (2-D) fuzzy-logic optical controller. The
      complexity of such a setup when we deal with an N-dimensional control procedure
      leads to a more compact version both in planning demands and in space. Viewing
      the pros and cons of the 2-D setup, we seek a simpler model and find it in a one-
      dimensional (1-D) multilayer setup. Here we explain the process of finding the
      optimal 1-D setup and support the concept with true optical results. The new 1-D
      optical controller is modular and easy to build, and the results that it yields
      are quite satisfactory.

PMID- 18323922
TI  - Loop mirror laser neural network with a fast liquid-crystal display.
AB  - In our laser neural network (LNN) all-optical threshold action is obtained by
      application of controlled optical feedback to a laser diode. Here an extended
      experimental LNN is presented with as many as 32 neurons and 12 inputs. In the
      setup we use a fast liquid-crystal display to implement an optical matrix vector
      multiplier. This display, based on ferroelectric liquid-crystal material, enables
      us to present 125 training examples/s to the LNN. To maximize the optical
      feedback efficiency of the setup, a loop mirror is introduced. We use a delta
      rule learning algorithm to train the network to perform a number of functions
      toward the application area of telecommunication data switching.

PMID- 18323923
TI  - Effect of beam profile on the cross talk of land and groove recording.
AB  - Numerical analyses were conducted to simulate the effects of different Gaussian
      weighted beams and disk geometries on the read-out signal cross talk of land and
      groove recording of phase-change optical disk systems. The optimized groove
      depth, which yields a minimum cross-talk noise, differs for different Gaussian
      weighted beams and different track pitches. This beam profile dependence of the
      optimum groove depth is undesirable for practical application of this technique,
      because different optical systems may have different beam profiles at the lens
      aperture plane. It is found that this effect can be reduced to a certain extent
      by introduction of an appropriate shading band filter.

PMID- 18323924
TI  - Channel modeling and estimation for intrapage equalization in pixel-matched
      volume holographic data storage.
AB  - We present two different channel models (the magnitude model and the intensity
      model) for a pixel-matched volume holographic data storage system that employs
      the 4-focal-length architecture. First, a framework to describe the channel
      models is developed. We evaluate the linearity of the channel models by comparing
      data values obtained from diffraction-limited interference with data values
      predicted by the channel models. The models are evaluated for linearity and
      equalization gain under different storage and read-back conditions, such as fill
      factors, apertures, and contrast ratios. Bit error rate results obtained by use
      of linear equalization methods in conjunction with the channel models developed
      are also presented. Our results suggest that the magnitude model leads to better
      performance when the fill factors are small, whereas the intensity model appears
      to be more appropriate for the high-fill-factor cases. The magnitude model, when
      suitable, appears to provide a storage density improvement of as great as 65%,
      whereas the intensity model seems capable of providing as much as 15% density
      gain through deconvolution. The optimum aperture for storage seems to be close to
      the Nyquist aperture.

PMID- 18323925
TI  - Application of linear minimum mean-squared-error equalization for volume
      holographic data storage.
AB  - When target densities of volume holographic data storage systems are increased,
      the systems experience increased interference from adjacent pixels and noise.
      Here we present a method for designing and applying linear minimum mean-squared
      error (LMMSE) equalization to improve the bit error rates (BER's) and hence the
      storage densities achievable. Numerical results with five defocused data pages
      indicate that a significant improvement in the BER is possible with LMMSE
      equalization.

PMID- 18323926
TI  - Evaluation of partial-response maximum-likelihood detection for phase-change
      optical data storage.
AB  - We describe the application of partial-response (PR) maximum-likelihood (ML)
      detection in rewritable phase-change optical data storage. The input to this
      detector, which is simulated in software, is the actual signal (without any
      equalization), reproduced from reading of the recorded sequence on an optical
      disk. The detection algorithm involves the extraction of the impulse response
      from the readout signal, PR equalization, the adjustment of gain and recovery of
      clock, ML sequence estimation with the Viterbi algorithm, and analysis of PRML
      performance. With a laser wavelength of 0.69 microm and an objective lens with a
      numerical aperture of 0.6, three linear densities are examined: 0.35 and 0.31
      microm/bit without modulation code and 0.2 microm/bit with the (1, 7) modulation
      code. The equalized signal exhibits good eye patterns, especially at the
      densities of 0.35 and 0.31 microm/bit. Analyses of noise and bit-error rate
      indicate that jitter, rather than noise, is the main obstacle to realizing
      ultrahigh density in phase-change media with PRML detection. We also briefly
      discuss the problem of the inherent nonlinear effect in phase-change readout.

PMID- 18323927
TI  - Comparison of various linear depolarization parameters measured by lidar.
AB  - Different definitions for estimating the degree of changes in signal polarization
      measured by lidar measurements are used both to detect the presence of
      nonspherical aerosol particles and to estimate their shape and density. Our aim
      is to provide a tool for calculation and interpretation of changes in
      polarization that are due to aerosol backscatter measured by the lidar technique.
      An overview of several techniques used to calculate linear depolarization from
      two-channel lidar measurements is given. Advantages and disadvantages of each
      method are analyzed when we apply them on a lidar vertical profile. Systematic
      errors are also discussed. First, an overview of different estimations of
      polarizability of atmospheric molecules is given. The presence of signal with
      orthogonal polarization in each channel (cross talk) is a source of error in
      depolarization estimation. It is calculated at various degrees of contamination,
      and the total uncertainty on depolarization definition is retrieved.

PMID- 18323928
TI  - Extraction of motion parameters of gravity-wave structures from all-sky OH image
      sequences.
AB  - We describe the application of a motion model to OH images collected by CCD
      cameras during three nights in February and April 1995 (3 February, 1 April, and
      4 April) at the StarFire Optical Range, New Mexico. We used the instrument to
      take broadband images of OH Meinel bands at an altitude of 87 km to record the
      footprints of dynamics created by acoustic gravity waves in the mesosphere. We
      used the motion model to extract the velocity of the gravity waves from the
      images. The results of a total of 181 observations with the motion model were
      compared with a total of 189 observations obtained by manual estimation. We used
      these results to extract the intrinsic properties of the gravity waves. The mean
      intrinsic velocity for the three nights under consideration was 61.5 +/- 17.0 m/s
      with the motion model and 61.1 +/- 23.3 m/s with manual estimation.

PMID- 18323929
TI  - Solar actinic flux spectroradiometry: a technique for measuring photolysis
      frequencies in the atmosphere.
AB  - A spectroradiometer has been developed for direct measurement of the solar
      actinic UV flux (scalar intensity) and determination of photolysis frequencies in
      the atmosphere. The instrument is based on a scanning double monochromator with
      an entrance optic that exhibits an isotropic angular response over a solid angle
      of 2pi sr. Actinic flux spectra are measured at a resolution of 1 nm across a
      range of 280-420 nm, which is relevant for most tropospheric photolysis
      processes. The photolysis frequencies are derived from the measured radiation
      spectra by use of published absorption cross sections and quantum yields. The
      advantage of this technique compared with the traditional chemical actinometry is
      its versatility. It is possible to determine the photolysis frequency for any
      photochemical reaction of interest provided that the respective molecular
      photodissociation parameters are known and the absorption cross section falls
      within a wavelength range that is accessible by the spectroradiometer. The
      instrument and the calibration procedures are described in detail, and problems
      specific to measurement of the actinic radiation are discussed. An error analysis
      is presented together with a discussion of the spectral requirements of the
      instrument for accurate measurements of important tropospheric photolysis
      frequencies (J(O(1))(D), J(NO(2)), J(HCHO)). An example of measurements from
      previous atmospheric chemistry field campaigns are presented and discussed.

PMID- 18323930
TI  - Error analysis for the lidar backward inversion algorithm.
AB  - Here we depart from the inhomogeneous solution of a lidar equation using the
      backward inversion algorithm that is nowadays generally referred to as the Klett
      method. In particular, we develop an error sensitivity study that relates errors
      in the user-input parameters boundary extinction and exponential term in the
      extinction-to-backscatter relationship to errors in the inverted extinction
      profile. The validity of the analysis presented is limited only by the validity
      of application of the inversion algorithm itself, its numerical performance
      having been tested for optical depths in the 0.01-10 range. Toward this end, we
      focus on an introductory background about how uncertainties in these two
      parameters can apply to a family of inverted extinction profiles rather than a
      single profile and on its range-dependent behavior as a function of the optical
      thickness of the lidar inversion range. Next, we performed a mathematical study
      to derive the error span of the inverted extinction profile that is due to
      uncertainties in the above-mentioned user calibration parameters. This takes the
      form of upper and lower range-dependent error bounds. Finally, appropriate
      inversion plots are presented as application examples of this study to a
      parameterized set of atmospheric scenes inverted from both synthesized elastic
      backscatter lidar signals and a live signal.

PMID- 18323931
TI  - Optical model for use in oceanic ecosystem models.
AB  - Modeling the plankton ecosystem requires a code for simulating the profile of
      irradiance from the chlorophyll profile at each time step of the integration. We
      have compared two existing codes with data from the Biogeochemical Ocean Flux
      Study: the Hydrolight radiative transfer model is accurate but too slow to use
      interactively in ecological models; Morel's [J. Geophys. Res. 93, 10, 749 (1988)]
      empirical model is much faster but produces substantial error. We have developed
      a streamlined version of the Hydrolight radiative transfer model that is 20 times
      faster than the full Hydrolight code, while limiting errors to less than 12%
      within the euphotic zone. This new code is both fast and accurate and is,
      therefore, suitable for use interactively in oceanic ecosystem models.

PMID- 18323932
TI  - Processing and characterization of silver films used to fabricate hollow glass
      waveguides.
AB  - Hollow glass waveguides are an increasingly popular fiber for the delivery of
      high-power IR laser radiation. At CO(2) laser wavelengths the measured and
      theoretical losses agree, but at the 3-microm Er:YAG laser wavelength the losses
      remain higher than expected. The reason for this is the surface roughness of the
      silver film used to form the first layer of the Ag/AgI thin-film structure. We
      found that the roughness of the silver film increases fivefold as silvering times
      increase from 5 to 80 min. This increased surface roughness produces a
      concomitant linear increase in the attenuation coefficient for the silver-only
      guides for wavelengths shorter than approximately 5 microm.

PMID- 18323933
TI  - Reconstruction of fiber grating refractive-index profiles from complex bragg
      reflection spectra.
AB  - Reconstruction of the refractive-index profiles of fiber gratings from their
      complex Bragg reflection spectra is experimentally demonstrated. The amplitude
      and phase of the complex reflection spectrum were measured with a balanced
      Michelson interferometer. By integrating the coupled-mode equations, we built the
      relationship between the complex coupling coefficient and the complex reflection
      spectrum as an iterative algorithm for reconstructing the index profile. This
      method is expected to be useful for reconstructing the index profiles of fiber
      gratings with any apodization, chirp, or dc structures. An apodized chirped
      grating and a uniform grating with a depression of index modulation were used to
      demonstrate the technique.

PMID- 18323934
TI  - Wavelength-encoding/temporal-spreading optical code division multiple-access
      system with in-fiber chirped moire gratings.
AB  - We propose an optical code division multiple-access (OCDMA) system that uses in
      fiber chirped moire gratings (CMG's) for encoding and decoding of broadband
      pulses. In reflection the wavelength-selective and dispersive nature of CMG's can
      be used to implement wavelength-encoding/temporal-spreading OCDMA. We give
      examples of codes designed around the constraints imposed by the encoding devices
      and present numerical simulations that demonstrate the proposed concept.

PMID- 18323935
TI  - Analysis of mode size transformation with a tapered directional coupler.
AB  - A simple tapered directional coupler with a five-layered structure is employed
      for mode conversion between a single-order and higher-order modes. We investigate
      coupling from higher-order modes to a single-order field theoretically and
      experimentally. As a result, we confirm that the first two modes in the tapered
      waveguide are coupled with a single-order mode in another waveguide by computer
      simulation using the beam propagation method. Furthermore, we fabricated the
      actual device and observed the streak patterns of the first three modes.

PMID- 18323936
TI  - Performance of Nd:YAG lasers in coupled generalized self-filtering and positive
      branch unstable resonators.
AB  - A new optical resonator based on the combination of a generalized self-filtering
      unstable resonator (GSFUR) and a positive-branch unstable resonator (PBUR) in a
      three-mirror scheme is reported. It is shown both theoretically and
      experimentally that a nearly diffraction-limited Gaussian-output laser beam with
      a large mode volume can be obtained with this cavity design. The laser cavity is
      particularly interesting for use in high-threshold pumped gain media and
      eliminates some disadvantages of the SFUR and GSFUR designs. This resonator, with
      an effective magnification of -6.16, was applied to a pulsed Nd:YAG laser in free
      running and in Q-switched modes of operation. The output energy was approximately
      70 mJ, 5.5 times greater than when a single GSFUR design was used. The output
      beam had a pulse duration of approximately 30 ns in the Q-switched mode of
      operation and a beam divergence of 0.26 mrad. The required relations for the
      GSFUR-PBUR optical design and the output energy were derived and verified
      experimentally.

PMID- 18323937
TI  - Design of low-haze holographic notch filters.
AB  - We have studied the optical quality of holographic notch filters and have
      identified that stray illumination during the exposure stage and substrate
      scatter are the limiting factors. We propose and analyze a novel holographic
      recording scheme in which the substrate is rotated during exposure. Using this
      method, we have produced high-uniformity, flare-free dichromated gelatin notch
      filters with optical density greater than 5 and with scatter comparable with that
      from polished substrates.

PMID- 18323938
TI  - Properties of Nd3+-doped and undoped tetragonal PbWO4, NaY(WO4)2, CaWO4, and
      undoped monoclinic ZnWO4 and CdWO4 as laser-active and stimulated raman
      scattering-active crystals.
AB  - Spectroscopic, laser, and chi((3)) nonlinear optical properties of tetragonal
      PbWO(4), NaY(WO(4))(2), CaWO(4), and monoclinic CdWO(4) and ZnWO(4) were
      investigated. Particular attention was paid to Nd(3+)-doped and undoped PbWO(4)
      and NaY(WO(4))(2) crystals. Their absorption and luminescence intensity
      characteristics, including the peak cross sections of induced transitions, were
      determined. Pulsed and continuous-wave lasing in the two 4F(3/2)-->4I(11/2) and
      4F(3/2)-->4I(13/2) channels was excited. For these five tungstates, highly
      efficient (greater than 50%) multiple Stokes generation and anti-Stokes
      picosecond generation were achieved. All the observed scattered laser components
      were identified. These results were analyzed and compared with spectroscopic data
      from spontaneous Raman scattering. A new crystalline Raman laser based on PbWO(4)
      was developed for the chi((3)) conversion frequency of 1-microm pump radiation to
      the first Stokes emission with efficiency up to 40%. We classify all the
      tungstates as promising media for lasers and neodymium-doped crystals for self
      stimulated Raman scattering lasers.

PMID- 18323939
TI  - High-repetition rate 1-J green laser system.
AB  - A laser-diode-pumped high-repetition-rate zigzag slab Nd:YAG oscillator-amplifier
      system is developed as the pumping source of a high-average-power and terawatt
      Ti:sapphire chirped pulse amplification laser system. This system can produce a
      greater than 2-J high-energy fundamental laser pulse at a repetition rate of 100
      Hz. The frequency-doubled energy with a diffusion-bonded KTP crystal is 1 J at a
      repetition rate of 100 Hz.

PMID- 18323940
TI  - Extraction of high-quality beams from narrow annular laser sources.
AB  - We have analyzed the propagation properties of the field produced by circular
      arrays of coherent optical sources, obtaining the conditions for the generation
      of good-quality global beams. Such conditions can be obtained by the use of
      resonators based on the Talbot effect. This appears to be a practical method for
      the construction of simple, low-cost resonators for compact diffusion-cooled high
      power lasers with annular format. Low-loss annular Talbot cavity configurations
      have also been studied.

PMID- 18323941
TI  - Characterization of fiber distributed-feedback lasers with an index-perturbation
      method.
AB  - We demonstrate the characterization of fiber distributed-feedback lasers by
      scanning a heat-induced index perturbation along the cavity and by measuring the
      induced laser frequency shift. The measured shift is shown to be a good indicator
      for the intensity distribution in the cavity, and the experimental results reveal
      that the sensitivity of fiber distributed-feedback laser sensors with frequency
      readout is highly localized near the grating phase-shift position. Use of the
      characterization data to determine the grating coupling parameter kappa, the
      polarization dependence of kappa, and birefringence nonuniformities as well as
      for identification of the order of longitudinal mode operation are discussed and
      demonstrated experimentally. Asymmetrically phase-shifted lasers with highly
      directional output are also investigated.

PMID- 18323942
TI  - Unidirectional single-mode Nd:YAG laser with a planar semimonolithic ring cavity.
AB  - Unidirectional single-mode operation of a diode-pumped Nd:YAG laser with a planar
      semimonolithic ring cavity has been demonstrated at 1064 nm. The semimonolithic
      cavity consists of a laser active medium placed in a magnetic field, a crystal
      quartz plate, and an output coupling mirror, which form an optical diode by
      acting as a Faraday rotator, a reciprocal polarization rotator, and a partial
      polarizer, respectively. A single-mode output power of 155 mW and a slope
      efficiency of 17% were obtained with a 1.2-W diode laser at 809 nm. A laser
      linewidth of less than 100 kHz is inferred from a beat note frequency spectrum
      between two identical laser systems and continuous tuning to greater than 2 GHz
      was observed.

PMID- 18323943
TI  - Laser heat treatments driven by integrated beams: role of irradiation
      nonuniformities.
AB  - An analysis is given of how nonuniformities in the laser beam intensity translate
      into variations on the induced temperature distribution on an irradiated sample.
      The study involves materials with different thermal conductivities. By use of a
      reshaped irradiating beam obtained with a multifaceted integrating mirror, a
      three-dimensional numerical calculation allows us to establish both surface and
      in-depth temperature distributions. The results show that in the case of
      materials such as glass (i.e., with low thermal conductivity) large thermal
      gradients occur both on the surface and in depth during irradiation. However, the
      lateral heat flow is high enough to strongly reduce the surface gradients as soon
      as the laser irradiation ends. Conversely, in good thermal conductors such as
      nickel, the laser intensity nonuniformities induce a thermal peaking of the
      surface with lateral thermal gradients that are by no means negligible.
      Experimental evidence during laser glass polishing that confirms the numerical
      assessments are also provided.

PMID- 18323944
TI  - Thermo-optic dispersion formula for AgGaS2.
AB  - AgGaS(2) has been found to be 90 degrees phase matchable at 192 degrees C for sum
      frequency mixing between the output of the KTP parametric oscillator at 3.2627
      microm and its pump source at 1.0642 microm. The thermo-optic dispersion formula
      that can be used for good reproduction of the temperature-dependent phase
      matching conditions thus far reported in the literature as well as our new data
      for second-harmonic generation of a CO(2) laser and its harmonics at 1.7652
      5.2955 microm is presented.

PMID- 18323945
TI  - Far-field intensity distribution, M2 factor, and propagation of flattened
      Gaussian beams.
AB  - Explicit expressions for the M(2) factor and field distribution of flattened
      Gaussian beams that propagate through an unapertured paraxial ABCD system are
      derived and illustrated with numerical examples. We show that the far-field
      expression of flattened Gaussian beams can be readily obtained by use of our
      results.

PMID- 18323946
TI  - Aerosol observations by lidar in the nocturnal boundary layer.
AB  - Aerosol observations by lidar in the nocturnal boundary layer (NBL) were
      performed in Potenza, Southern Italy, from 20 January to 20 February 1997.
      Measurements during nine winter nights were considered, covering a variety of
      boundary-layer conditions. The vertical profiles of the aerosol backscattering
      coefficient at 355 and 723.37 nm were determined through a Klett-modified
      iterative procedure, assuming the extinction-to-backscattering ratio within the
      NBL has a constant value. Aerosol average size characteristics were retrieved
      from almost simultaneous profiles of the aerosol backscattering coefficient at
      355 and 723.37 nm, the measurements being consistent with an accumulation mode
      radius not exceeding 0.4 microm. Similar results in terms of aerosol sizes were
      obtained from measurements of the extinction-to-backscattering ratio profile at
      355 nm performed on six nights during the measurement campaign. Backscattering
      profiles at 723.37 nm were also converted into profiles of aerosol liquid water
      content.

PMID- 18323947
TI  - Quantitative hydroxyl concentration time-series measurements in turbulent
      nonpremixed flames.
AB  - Quantitative hydroxyl concentration time-series measurements have been obtained
      by picosecond time-resolved laser-induced fluorescence in a series of methane-air
      and hydrogen-argon-air nonpremixed flames. The recovery of a quantitative time
      series is complicated by the need to account for fluctuations in the fluorescence
      lifetime. We have recently developed instrumentation that enables the
      simultaneous measurement of fluorescence signal and lifetime. The present
      research represents the first application of this technique to turbulent flames.
      The correction for hydroxyl lifetime fluctuations is shown to be significant for
      mean concentrations and thus probability density functions but negligible for
      power spectral densities (PSD's). The hydroxyl PSD's were found to vary slightly
      with radial and axial location in the flames and to vary significantly with
      Reynolds number. However, the PSD's in the H(2)-Ar-air flames are nearly
      identical to those in the CH(4)-air flames.

PMID- 18323948
TI  - Airborne laser infrared absorption spectrometer (ALIAS-II) for in situ
      atmospheric measurements of N2O, CH4, CO, HCl, and NO2 from balloon or remotely
      piloted aircraft platforms.
AB  - The Airborne Laser Infrared Absorption Spectrometer II (ALIAS-II) is a
      lightweight, high-resolution (0.0003-cm(-1)), scanning, mid-infrared absorption
      spectrometer based on cooled (80 K) lead-salt tunable diode laser sources. It is
      designed to make in situ measurements in the lower and middle stratosphere on
      either a balloon platform or high-altitude remotely piloted aircraft. Chemical
      species that can be measured precisely include long-lived tracers N(2)O and
      CH(4), the shorter-lived tracer CO, and chemically active species HCl and NO(2).
      Advances in electronic instrumentation developed for ALIAS-I, with the experience
      of more than 250 flights on board NASA's ER-2 aircraft, have been implemented in
      ALIAS-II. The two-channel spectrometer features an open cradle, multipass
      absorption cell to ensure minimal contamination from inlet and surfaces. Time
      resolution of the instrument is <or=3 s, allowing rapid in situ measurements with
      excellent spatial resolution. ALIAS-II has completed successful balloon flights
      from New Mexico, Alaska, and Brazil providing CH(4) and N(2)O vertical profiles
      in the tropics, mid-latitudes, and high northern latitudes up to altitudes of 32
      km.

PMID- 18323949
TI  - Electro-optic lightning detector.
AB  - The design, alignment, calibration, and field deployment of a solid-state
      lightning detector is described. The primary sensing component of the detector is
      a potassium dihydrogen phosphate electro-optic crystal that is attached in series
      to a flat-plate aluminum antenna; the antenna is exposed to the ambient
      thundercloud electric field. A semiconductor laser diode (lambda = 685 nm),
      polarizing optics, and the crystal are arranged in a Pockels cell configuration.
      Lightning-caused electric field changes are related to small changes in the
      transmission of laser light through the optical cell. Several hundred lightning
      electric field change excursions were recorded during five thunderstorms that
      occurred in the summer of 1998 at the NASA Marshall Space Flight Center in
      northern Alabama.

PMID- 18323950
TI  - Use of a Fabry-Perot interferometer to isolate pure rotational Raman spectra of
      diatomic molecules.
AB  - We propose to use a Fabry-Perot interferometer (FPI) as a comb frequency filter
      to isolate pure rotational Raman spectra (PRRS) of nitrogen molecules. In making
      the FPI's free spectral range equal to the spectral spacing between the lines of
      nitrogen PRRS, which are practically equidistant, one obtains a device with a
      comb transmission function with the same period. However, to match the FPI
      transmission comb completely with the comb of nitrogen PRRS lines one should tune
      the wavelength of the radiation used to excite the PRRS of nitrogen exactly to
      the position of any minimum in the FPI transmission comb. Thus to achieve this
      task for the case of nitrogen PRRS one must take the FPI's free spectral range
      Dnu(f)= 4B(N(2)) and the wavelength of the exciting radiation such that
      (1/lambda(exc)) = 4B(N(2))(k + 1/2), where B(N(2)) is the rotational constant of
      the nitrogen molecule and k is an arbitrary integer number. In this case all (odd
      and even) pure rotational Raman lines of nitrogen will pass through the FPI while
      the line of exciting radiation is being suppressed. Additionally, a FPI cuts out
      the spectrally continuous sky background light from the spectral gaps between the
      PRRS lines.

PMID- 18323951
TI  - Signal-induced fluorescence in photomultipliers in differential absorption lidar
      systems.
AB  - Signal-induced bias (SIB) superimposed on the tail of lidar signals detected by
      photomultiplier tubes (PMT's) has long been recognized as significant
      interference in lidar data retrieval. Analysis of the data from a lidar
      transmitting in the horizontal direction revealed that SIB is a well-shaped pulse
      and is thus called a signal-induced pulse (SIP). The SIP starts near the end of
      the signal and has an exponentially decaying tail. The decay time constant is
      negatively correlated with the pulse rise time. The origins of afterpulses
      discussed in the literature could not explain the cause of the SIP. This research
      leads to the hypothesis that the SIP is the fluorescence emitted from the PMT
      wall that is impinged by ions in the PMT. A model was developed, and the results
      show good agreement with the data. This model is applied to remove SIP's during
      processing of data from an ozone-profiling lidar.

PMID- 18323952
TI  - Changes in the Radiometric sensitivity of SeaWiFS determined from lunar and solar
      based measurements.
AB  - We report on the lunar and solar measurements used to determine the changes in
      the radiometric sensitivity of the Sea-viewing Wide Field-of-view Sensor
      (SeaWiFS). Radiometric sensitivity is defined as the output from the instrument
      (or from one of the instrument bands) per unit spectral radiance at the
      instrument's input aperture. Knowledge of the long-term repeatability of the
      SeaWiFS measurements is crucial to maintaining the quality of the ocean scenes
      derived from measurements by the instrument. For SeaWiFS bands 1-6 (412-670 nm),
      the change in radiometric sensitivity is less than 0.2% for the period from
      November 1997 through November 1998. For band 7 (765 nm), the change is
      approximately 1.5% and for band 8 (865 nm) approximately 5%. The rates of change
      of bands 7 and 8, which were linear with time for the first eight months of lunar
      measurements, are now slowing. The scatter in the data points about the trend
      lines in this analysis is less than 0.3% for all eight SeaWiFS bands. These
      results are based on monthly measurements of the moon. Daily solar measurements
      using an onboard diffuser show that the radiometric sensitivities of the SeaWiFS
      bands have changed smoothly during the time intervals between lunar measurements.
      Because SeaWiFS measurements have continued past November 1998, the results
      presented here are considered as a snapshot of the instrument performance as of
      that date.

PMID- 18323953
TI  - High capacity optical beam forming for phased arrays with fiber gratings and
      frequency conversion for beat noise control.
AB  - A new wavelength division multiplexing grating-based beam-forming architecture
      for phased arrays that can achieve the minimum possible number of optical
      interconnects is presented. A reduction in interconnect hardware of 99.6% is
      obtained for a 512-beam array, which is, as far as we know, the lowest number of
      interconnects reported to date. Analysis of the ultimate beam capacity limit of
      the beam former shows that the beat noise interference limitation is the most
      important factor. We present a new hybrid frequency-converting optical beam
      former that removes the fundamental beat noise limitation. This frequency
      downconverts the rf signal to an intermediate frequency before performing the
      true-time-delay equalization in the optical domain. The resulting advantage of
      reduced optical bandwidth per channel enables more wavelengths to be used for a
      given wavelength span, resulting in an increased beam capacity. A greater than
      sevenfold increase in beam capacity is demonstrated through the use of the
      frequency conversion technique, with 960 beams synthesized at 12.4 GHz, showing a
      99.8% reduction in required interconnects.

PMID- 18323954
TI  - Influence of correlated errors on the estimation of the relaxation time spectrum
      in dynamic light scattering.
AB  - An important step in analyzing data from dynamic light scattering is estimating
      the relaxation time spectrum from the correlation time function. This estimation
      is frequently done by regularization methods. To obtain good results with this
      step, the statistical errors of the correlation time function must be taken into
      account [J. Phys. A 6, 1897 (1973)]. So far error models assuming independent
      statistical errors have been used in the estimation. We show that results for the
      relaxation time spectrum are better if correlation between statistical errors is
      taken into account. There are two possible ways to obtain the error sizes and
      their correlations. On the one hand, they can be calculated from the correlation
      time function by use of a model derived by Schatzel. On the other hand, they can
      be computed directly from the time series of the scattered light. Simulations
      demonstrate that the best results are obtained with the latter method. This
      method requires, however, storing the time series of the scattered light during
      the experiment. Therefore a modified experimental setup is needed. Nevertheless
      the simulations also show improvement in the resulting relaxation time spectra if
      the error model of Schatzel is used. This improvement is confirmed when a lattice
      with a bimodal sphere size distribution is applied to experimental data.

PMID- 18323955
TI  - Size, velocity, and concentration in suspension measurements of spherical
      droplets and cylindrical jets.
AB  - The principle of an optical technique for simultaneous velocity, size, and
      concentration in suspension measurements of spherical droplets and cylindrical
      jets is proposed. This technique is based on phase Doppler anemometry working in
      the dual burst technique configuration. The particle size and velocity are
      deduced from the reflected signal phase and frequency, whereas the amplitude
      ratio between the refracted and the reflected signals is used for measuring the
      concentration of small scatterers inside the particles. Numerical simulations,
      based on geometrical optics and a Monte Carlo model, and an experimental
      validation test on cylindrical jets made of various suspensions, are used to
      validate the principle of the proposed technique. It is believed that this new
      technique could be useful in investigating processes in which liquid suspensions
      are sprayed for surface coating, drying, or combustion applications.

PMID- 18323956
TI  - On-line multicomponent trace-gas analysis with a broadly tunable pulsed
      difference-frequency laser spectrometer.
AB  - The design and application of a novel automated room-temperature laser
      spectrometer are reported. The compact instrument is based on difference
      frequency generation in bulk LiNbO(3). The instrument employs a tunable cw
      external-cavity diode laser (795-825 nm) and a pulsed diode-pumped Nd:YAG laser
      (1064 nm). The generated mid-IR nanosecond pulses of 50-microW peak power and 6.5
      kHz repetition rate, continuously tunable from 3.16 to 3.67 microm, are coupled
      into a 36-m multipass cell for spectroscopic studies. On-line measurements of
      methane are performed at concentrations between 200 ppb (parts in 10(9) by mole
      fraction) and approximately 1%, demonstrating a large dynamic range of 7 orders
      of magnitude. Furthermore computer-controlled multicomponent analysis of a
      mixture containing five trace gases and water vapor with an overall response time
      of 90 s at an averaging time of only approximately 30 s is reported. A minimum
      detectable absorption coefficient of 1.1 x 10(-7) cm(-1) has been achieved in an
      averaging time of 60 s, enabling detection limits in the ppb range for many
      important trace gases, such as CH(4), C(2)H(6), H(2)CO, NO(2), N(2)O, HCl, HBr,
      CO, and OCS.

PMID- 18323957
TI  - Development of an IR tunable diode laser absorption spectrometer for trace
      humidity measurements at atmospheric pressure.
AB  - The development of a laser diode absorption spectrometer that uses a strong water
      vapor absorption at 1393 nm is reported. Three spectroscopic techniques were
      compared in approximately 0.4 m of laboratory air, namely, frequency modulation,
      wavelength modulation, and two-tone frequency modulation spectroscopy. The first
      two techniques use a single-frequency modulation at 9.2 GHz and 1 kHz,
      respectively, generated either by a phase modulator operating at 9.2 GHz or
      injection current modulation at 1 kHz. The two-tone method requires modulation at
      two frequencies, in this case 9.19 and 9.21 GHz. It is shown that the two-tone
      method should provide the highest sensitivity for a trace moisture detection
      system.

PMID- 18323958
TI  - Dinitrobenzene detection by use of one-color laser photolysis and laser-induced
      fluorescence of vibrationally excited NO.
AB  - Trace concentrations of 1, 4-dinitrobenzene (DNB) are detected by a combination
      of laser photolysis and laser-induced fluorescence. A one-color laser is applied
      to induce DNB photodissociation and for subsequent detection of NO photofragments
      by excitation and emission through A(v' =0) <-- X(v" = 0 - 2) and A(v' =0) -->
      X(v" = 0,1) transitions, respectively. The resulting NO rovibrational excitation
      spectra serve as markers for the presence of DNB. The NO is produced in
      vibrational ground and excited states with peak height ratios of (v" = 0):(v" =
      1):(v" = 2) = 1:0.5:0.13. The limits of detection of DNB mixed with 100 or 500
      Torr of air with v" = 2 excitation at 248 nm are 13 and 11 parts in 10(9) by
      weight, respectively, for a 30-s integration time. The application of this scheme
      for DNB detection has the advantage that no ambient ground state NO interferes
      and that the fluorescence is collected at shorter wavelengths than the exciting
      radiation, precluding background fluorescence.

PMID- 18323959
TI  - Highly dispersive mirror in Ta2O5/SiO2 for femtosecond lasers designed by inverse
      spectral theory.
AB  - A highly dispersive mirror for dispersion compensation in femtosecond lasers is
      designed by inverse spectral theory. The design of a simple quarter-wave Bragg
      reflector can be modified by moving the poles in the optical impedance found in
      the photonic stop band. These spectral quantities are used as independent
      variables in the numerical optimization because they have no effect on the
      location of the photonic stop band, and so the design requirements to obtain a
      high reflectivity and a specific delay spectrum are decoupled. The design was
      fabricated by ion-beam sputtering. A group delay dispersion of -300 fs(2) was
      measured over a bandwidth of 28 nm, with a remaining reflectivity of greater than
      99% in this range. The mirrors were used to make two Ti:sapphire lasers with 10-
      and 4-mm-long crystals, both of which generated near-transform-limited pulses of
      35-fs duration. Because of the high dispersion of the mirrors, the laser cavities
      needed only five and three bounces from the mirrors, thus keeping reflection
      losses to a minimum.

PMID- 18323960
TI  - Surface damage of extreme-ultraviolet gratings exposed to high-energy 20-fs laser
      pulses.
AB  - The damage fluences of gratings for diffraction of ultraviolet radiation, which
      are used in high-order harmonic generation experiments, have been measured with
      respect to the fundamental laser beam radiation. We have tested gold and platinum
      coatings of 40- and 50-nm thickness, respectively, deposited onto fused-silica
      substrates, after irradiation of high-energy, spatially filtered, 20-fs laser
      pulses at 780 nm. The damage appears at a fluence of approximately 0.3 J cm(-2)
      for gold and at a fluence of approximately 0.4 J cm(-2) for platinum. Scanning
      electron microscopy of the irradiated regions revealed different damaging
      mechanisms for the two coatings.

PMID- 18323961
TI  - Control of the Responsivity and the detectivity of superconductive edge
      transition YBa2Cu3O7-x bolometers through substrate properties.
AB  - The detectivity D* limits of YBa(2)Cu(3)O(7-x) bolometers on 0.05-cm-thick
      crystalline substrates are investigated, and a method to increase D* to greater
      than 10(9) (cm Hz(1/2))/W at a 20-microm wavelength is proposed. Because the
      response increases proportionally with the bias current I(b), whereas the noise
      near T(c) (the transition or critical temperature) of our MgO and SrTiO(3)
      substrate samples does not, an increase in D* of these samples is obtained by an
      increase in I(b). Another limiting factor is the dc thermal conductance G(0) of
      the device, which, although controlled by the substrate-holder thermal boundary
      resistance for our samples, can be changed by means of thinning the substrate to
      increase D*. The optimal amount of thinning depends on the substrate's thermal
      parameters and the radiation modulation frequency. D* in our samples is also
      found to follow the spectral-radiation absorption of the substrate material.

PMID- 18323962
TI  - Cylindrical-type nanometer-resolution laser diffractive optical encoder.
AB  - A new, to our knowledge, design for a cylindrical-type diffractive optical
      encoder is proposed. The wave-front aberrations induced by the power of the
      rotation disk in this encoder can be canceled out completely. Wave-front
      aberration cancellation and desensitization to the grating misalignment are
      achieved by means of positioning the virtual point source, which was induced by
      the cylindrical grating with respect to two sets of modified telescopes with a
      magnification ratio of one: 1x telescopes. For evaluating the performance
      envelope of this newly designed optical system a code v-based optical-design
      software program was adopted to simulate the performance of the optical system.
      From tolerance-analysis results it was found that this newly developed
      cylindrical encoder system has the capability to compensate for most aberrations
      and, in addition, possesses a high tolerance for optical-component misalignment.
      For verifying the performance of the developed system the cylindrical diffractive
      encoder system was cross-referenced with a Hewlett-Packard Model HP-5529 laser
      interferometer positioning signal. The experimental results confirm the merits of
      this newly developed cylindrical encoder.

PMID- 18323963
TI  - Demodulation of fiber bragg grating sensors based on dynamic tuning of a
      multimode laser diode.
AB  - Dither demodulation of fiber Bragg grating sensors illuminated with multimode
      light from laser diodes is theoretically and experimentally investigated. Quasi
      static temperature and strain sensitivities of 0.09 degrees C/ radical Hz and 0.6
      microepsilon/ radical Hz are obtained. We show that it is possible to measure
      small ac signals that lie outside the feedback loop bandwidth by using a
      synchronous detection referenced to twice the dither frequency. In this
      situation, dynamic strain sensitivity of 3.3 n(epsilon)/ radical Hz is achieved.

PMID- 18323964
TI  - Three-dimensional object recognition by fourier transform profilometry.
AB  - An automatic method for three-dimensional (3-D) shape recognition is proposed. It
      combines the Fourier transform profilometry technique with a real-time
      recognition setup such as the joint transform correlator (JTC). A grating is
      projected onto the object surface resulting in a distorted grating pattern. Since
      this pattern carries information about the depth and the shape of the object,
      their comparison provides a method for recognizing 3-D objects in real time. A
      two-cycle JTC is used for this purpose. Experimental results demonstrate the
      theory and show the utility of the new proposed method.

PMID- 18323965
TI  - Optimization of graded multilayer designs for astronomical X-ray telescopes.
AB  - We developed a systematic method for optimizing the design of depth-graded
      multilayers for astronomical hard-x-ray and soft-gamma-ray telescopes based on
      the instrument's bandpass and the field of view. We apply these methods to the
      design of the conical-approximation Wolter I optics employed by the balloon-borne
      High Energy Focusing Telescope, using W/Si as the multilayer materials. In
      addition, we present optimized performance calculations of mirrors, using other
      material pairs that are capable of extending performance to photon energies above
      the W K-absorption edge (69.5 keV), including Pt/C, Ni/C, Cu/Si, and Mo/Si.

PMID- 18323966
TI  - Influence of Seidel distortion on combining beams from a phased telescope array.
AB  - When beams from an array of a focal telescopes are presented to a beam-combining
      telescope, tilt errors of the beam wave fronts with respect to the combined wave
      front place limits on the achievable field of view (FOV); these limits, to the
      best of our knowledge, have not previously been correctly described in the
      literature. We show that if the front-end telescopes have just the right Seidel
      distortion coefficient, then tilt error does not limit the FOV. If this is not
      the case, at least small FOV's can still be obtained, even if the FOV is not
      centered on the on-axis direction.

PMID- 18323967
TI  - Windows in ellipsometry measurements.
AB  - The effect of windows or lenses placed between the polarization-state generator
      and the polarization-state detector in a general ellipsometry measurement is
      examined. It is found that three parameters are required for describing the
      effects of the window retardation on the ellipsometry measurements. Two of these
      window parameters can be measured at the same time as the sample parameters if
      the sample is isotropic, but the third window parameter cannot be determined
      independently and must be measured separately. If the sample is anisotropic, then
      none of the windows parameters can be measured independently at the same time as
      the sample parameters. An example is given in which the strain-induced
      retardation in fused-silica focusing lenses is measured with a two-modulator
      generalized ellipsometer and the results are used to correct the sample data.

PMID- 18323968
TI  - Power spectral density analysis of optical substrates for gravitational-wave
      interferometry.
AB  - The power spectral density of surface-relief variations on polished optical
      surfaces across microscopic through to macroscopic spatial scales is calculated
      from measurements on substrates that are being produced for the Laser
      Interferometer Gravitational-Wave Observatory (LIGO). These spectra give a guide
      to the scattering properties of the surface, which in turn critically influence
      the performance of LIGO. Measurements obtained by use of a full-aperture
      interferometer and an interference microscope with two different objectives are
      combined to produce one-dimensional power spectral density representations of the
      surfaces across spatial frequencies ranging from 0.1 to 8000 cm(-1). These
      measurements from different instruments are in good agreement with an analytic
      power spectrum that varies as nu(-1.5), where nu is the spatial frequency. Some
      anomalies in the power spectral density spectra can be related to aspects of the
      polishing process.

PMID- 18323969
TI  - Spectroscopic generalized ellipsometry based on fourier analysis.
AB  - The extension of a spectroscopic ellipsometer that consists of a fixed polarizer,
      a rotating polarizer, a sample, and a fixed analyzer (PRPSE) to generalized
      ellipsometry to determining the generalized ellipsometric angles and the optical
      functions of an anisotropic medium is reported. The PRPSE configuration
      eliminates the polarization sensitivity of the light source. A general numerical
      technique has been derived to characterize the optical properties of the
      anisotropic material without intermediate generalized ellipsometric angles. The
      proposed method is experimentally verified for uniaxial mercuric iodide. The
      ordinary and the extraordinary refractive and absorption indices, respectively,
      N(o) = n(o)--ik(o) and N(e) = n(e)--ik(e), can be extracted directly from the
      Fourier coefficients measured by the PRPSE on a HgI(2) crystal face that contains
      the optical axis. The orientations of the optical axis with respect to the plane
      of incidence were also determined by direct analysis of the measured Fourier
      coefficients. Measurements were made of reflection across a spectral range of 1.5
      4.13 eV at one angle of incidence (Phi = 70 degrees ) for several azimuths phi of
      the optical axis with respect to the plane of incidence. The generalized
      ellipsometric angles were obtained from numerical inversion by changes of both
      polarizer and analyzer azimuth angles P and A.

PMID- 18323970
TI  - Digital recording and numerical reconstruction of lensless fourier holograms in
      optical metrology.
AB  - Advantages of the lensless Fourier holography setup for the reconstruction of
      digitally recorded holograms in holographic interferometry are presented. This
      very simple setup helps to achieve a maximum lateral resolution of the object
      under investigation. Also, the numerical-reconstruction algorithm is very simple
      and fast to compute. A mathematical model based on Fourier optics is used to
      describe discretization effects and to determine the lateral resolution. The
      recording and the reconstruction processes are regarded as an optical imaging
      system, and the point-spread function is calculated. Results are verified by an
      experimental setup for a combined shape and deformation measurement.

PMID- 18323971
TI  - Fiber distributed-feedback lasers used as acoustic sensors in air.
AB  - Contributions to the acoustic signal sensitivity of fiber distributed-feedback
      (DFB) lasers in air are investigated both theoretically and experimentally. The
      theoretical results show that the dominant contribution to the laser frequency
      shift comes from adiabatic temperature shifts in the surrounding air at lower
      frequencies and from pressure at higher frequencies. The transition frequency was
      found to be between 5 and 20 kHz, depending on the elastic boundary conditions of
      the fiber laser. The acoustically induced frequency shifts of two fiber DFB
      lasers were measured, and the sensitivities varied from 0.61 MHz/Pa at a 100-Hz
      acoustic frequency to 0.34 kHz/Pa at a 15-kHz acoustic frequency.

PMID- 18323972
TI  - Use of thin films for high-sensitivity angle measurement.
AB  - We propose to use thin films to provide a drastic improvement of measurement
      sensitivity in the recently developed small-angle measurement method, namely,
      angle measurement based on the internal-reflection effect. By designing the thin
      films (single layer or multiple layers) so that they provide an antireflection
      effect in the vicinity of the critical angle, we show that the sensitivity of
      angle measurement can be increased exponentially with the increase of the number
      of thin-film layers. This method provides a new means of designing angle sensors
      with increased sensitivities without having to increase the number of reflections
      and therefore the physical size and the required fabrication accuracy of the
      reflection prisms. We describe the design of the thin films for this particular
      application and the analysis of measurement sensitivity and range as determined
      by the material and the number of layers of the thin films. Selection of the
      optimal initial angle for high linearity performance is also discussed.

PMID- 18323973
TI  - Sensitivity of optical sensors based on laser-excited surface-plasmon waves.
AB  - We investigate the effect of the divergence of a Gaussian laser beam on the
      resonance curve and the sensitivity of optical sensors based on surface-plasmon
      resonance (SPR). For He-Ne laser beams it is found that, for beams with a waist
      radius of less than 300 microm, the SPR-curve characteristics differ appreciably
      from the case in which a plane wave is considered. Simple expressions for the
      sensitivity of (bio)chemical sensors are given. A simple Lorentzian model is used
      to estimate the maximum possible sensitivity when a multilayer system is used to
      enhance the resonance peak. It was found that the sensitivity can reach its
      highest value when the width of the SPR curve is equal to the laser-beam
      divergence. The results could be particularly important when a SPR curve is used
      to measure the absolute value of the refractive index of a sample or the
      dielectric constant and the thickness of a metal layer.

PMID- 18323974
TI  - Reflective grating interferometer: a folded reversal wave-front interferometer.
AB  - We present a new, folded reversal interferometer. It is based on the reflective
      grating interferometer and can be applied for optical isolation and testing of
      coma aberration. The interferometer has several advantages in respect to other
      existing optical reversal configurations. A carrier can be easily added for phase
      retrieval in interferometric fringe patterns for mapping coma aberration.
      Furthermore, in an asymmetric optical configuration a lateral shear can also be
      added, transforming it in a reversal shearing interferometer. The principle of
      operation of the interferometer is described, and the application for measuring
      the coma aberration of a parabolic mirror used off axis is demonstrated.

PMID- 18323975
TI  - Radiation-pressure-based cylindrically shaped microactuator capable of smooth,
      continuous, reversible, and stepped rotation.
AB  - Long cylindrical objects have been observed to align their central axis with the
      propagation axis of the illuminating laser beam through the action of radiation
      pressure-generated force and torque. A cylindrically shaped microactuator based
      on this principle and suitable for micromachine applications is examined
      theoretically. When four in-plane laser beams converging at a common point
      centered on the cylinder are used, the cylinder can be made to rotate about a
      pivot point. In one mode, smooth, continuous, and reversible rotation is
      possible, whereas the other cylinder can be step rotated and locked, similar to
      the operation of conventional stepping motors. The properties of the device are
      analyzed based on obtaining either a constant rotation rate with variable beam
      power levels or a quasi-constant rotation rate with constant beam power levels or
      on using a fixed beam sequence rate that matches the system parameters and
      produces smooth or stepped operation.

PMID- 18323976
TI  - Experimental confirmation of the optical-trapping properties of cylindrical
      objects.
AB  - A sophisticated modeling program was used recently to predict the trapping and
      the manipulation properties of elongated cylindrical objects in the focal region
      of a high-intensity laser beam. On the basis of the model, the cylinders should
      align their longest diagonal dimension with the propagation axis of the laser
      beam and follow the beam when it is displaced transverse to the cylinder's
      central axis. Experimental confirmation of the cylinder's behavior is presented
      and confirms the suitability of the enhanced ray-optics approach to modeling
      micrometer-scale objects in optical-trap environments.

PMID- 18323977
TI  - Confocal microscope with large field and working distance.
AB  - A confocal microscope that uses separate, noncollinear objective lenses for
      illumination and collection makes it possible to work 20 mm from a sample with a
      field of view of 2.25 mm across and still achieve lateral and axial resolutions
      below 5 microm. The design is expected to have application to in vivo confocal
      microscopy, allowing a field of view and section thickness similar to those used
      by pathologists in examining excised tissue.

PMID- 18323978
TI  - Analytical achromatic design of metal-dielectric absorbers.
AB  - Metal-dielectric coatings can be used successfully to design broadband absorbers.
      However, the understanding of the designs is not easy. Here we present a new
      analytical method using achromatic three-layer stacks. Such metal-dielectric
      basic structures permit movement from a fixed admittance value to another one
      over a wide spectral range. Efficient designs are calculated and explained with
      this method.

PMID- 18323979
TI  - Hexamethyldisiloxane film as the bottom antireflective coating layer for ArF
      excimer laser lithography.
AB  - We demonstrate a new bottom antireflective coating (BARC) layer for ArF excimer
      laser lithography. The antireflective layer is composed of hexamethyldisiloxane
      (HMDSO) film, which is deposited by the conventional electron cyclotron resonance
      plasma-enhanced chemical-vapor deposition process. We obtain the appropriate
      HMDSO films for BARC layers by varying the gas-flow rate ratio of oxygen to
      HMDSO. Such a process has several advantages: high deposition rate, low process
      temperature, easy film removal, and reduced cost. Measured reflectances of less
      than 0.5% on both Al-Si and silicon crystal substrates have been achieved and
      agree well with the simulated reflectances. The swing effect is shown to be
      significantly reduced by addition of the HMDSO-based BARC layer.

PMID- 18323980
TI  - Long-wavelength cutoff filters of a new type.
AB  - A method for the design of cutoff filters is proposed that is based on the use of
      light at nonnormal angles of incidence and on the use of coating materials with a
      large dispersion of the optical constants. The optical constants are presented of
      several films made from indium tin oxide--a material that satisfies this
      requirement. The filtering is due to absorption, critical angle effects, or both.
      The theory of this type of filter is described, and the calculated performance of
      two long-wavelength cutoff filters based on the use of indium tin oxide films is
      given. The angular performance and the producibility of one of these filters are
      examined. Some applications for these filters are considered, and the feasibility
      of producing similar filters for other spectral regions is discussed.

PMID- 18323981
TI  - Quantitative microspectrophotometry in turbid media.
AB  - We present a new technique to determine the scattering coefficient, the
      absorption coefficient, and the anisotropy factor in turbid media on a
      microscopic level. To this end, a microspectrophotometer was used to obtain
      transmission measurements at different solid angles. To extract the optical
      properties from phantom materials (liquid and solid) and biological tissue
      (bovine liver) an inverse Monte Carlo algorithm was used. The results obtained
      with the new microspectrophotometric technique agreed within one standard
      deviation with the values from Mie theory and within less than 10% with the data
      derived from conventional spectroscopic measurements. The results suggest that
      this new method is a valid tool to determine the optical properties of turbid
      media on a microscopic level.

PMID- 18323982
TI  - Triangulation method for determining capillary blood flow and physical
      characteristics of the skin.
AB  - A method capable of measuring blood flow at precise depths within the skin is
      described. The method determines the static and the dynamic properties of light
      that is backscattered to small areas on the surface of the skin at several
      contiguous locations along the expected trajectory of laser-light propagation.
      From observations the method has been shown to be capable of determining physical
      characteristics that are unique to the different layers of the skin.

PMID- 18323983
TI  - Measurement of the fluorescence lifetime in scattering media by frequency-domain
      photon migration.
AB  - A method is presented to determine fluorescence decay lifetimes within tissuelike
      scattering media. Fluorescence lifetimes are determined for micromolar
      concentrations of the dyes 3,3'-Diethylthiatricarbocyanine Iodide and Indocyanine
      Green by frequency-domain investigations of light propagating in turbid media.
      Dual-wavelength photon-migration measurements that use intensity-modulated
      sources at excitation and emission wavelengths of the fluorophores provide
      optical parameters of the media as well as fluorescence properties of the dyes.
      The deduction of fluorescence lifetimes requires no calibration with reference
      fluorophores, and the results are shown to be independent of dye concentration.

PMID- 18323984
TI  - In vivo local determination of tissue optical properties: applications to human
      brain.
AB  - Local and superficial near-infrared (NIR) optical-property characterization of
      turbid biological tissues can be achieved by measurement of spatially resolved
      diffuse reflectance at small source-detector separations (<1.4 mm). However, in
      these conditions the inverse problem, i.e., calculation of localized absorption
      and the reduced scattering coefficients, is necessarily sensitive to the
      scattering phase function. This effect can be minimized if a new parameter of the
      phase function gamma, which depends on the first and the second moments of the
      phase function, is known. If gamma is unknown, an estimation of this parameter
      can be obtained by the measurement, but the uncertainty of the absorption
      coefficient is increased. A spatially resolved reflectance probe employing
      multiple detector fibers (0.3-1.4 mm from the source) is described. Monte Carlo
      simulations are used to determine gamma, the reduced scattering and absorption
      coefficients from reflectance data. Probe performance is assessed by measurements
      on phantoms, the optical properties of which were measured by other techniques
      [frequency domain photon migration (FDPM) and spatially resolved transmittance].
      Our results show that changes in the absorption coefficient, the reduced
      scattering coefficient, and gamma can be measured to within +/-0.005 mm(-1), +/
      0.05 mm(-1), and +/-0.2, respectively. In vivo measurements performed
      intraoperatively on a human skull and brain are reported for four NIR wavelengths
      (674, 811, 849, 956 nm) when the spatially resolved probe and FDPM are used. The
      spatially resolved probe shows optimum measurement sensitivity in the measurement
      volume immediately beneath the probe (typically 1 mm(3) in tissues), whereas FDPM
      typically samples larger regions of tissues. Optical-property values for human
      skull, white matter, scar tissue, optic nerve, and tumors are reported that show
      distinct absorption and scattering differences between structures and a
      dependence on the phase-function parameter gamma.

PMID- 18323985
TI  - Absorption distribution of an optical beam focused into a turbid medium.
AB  - The focusing of light into a turbid medium was studied with Monte Carlo
      simulations. Focusing was found to have a significant effect on the absorption
      distribution in turbid media when the depth of the focal point (the distance
      between the focal point and the surface of the turbid media) was less than or
      comparable with the transport mean free path. Focusing could significantly
      increase the peak absorption and narrow the absorption distribution. As the depth
      of the focal point increased, the peak absorption decreased, and the depth of
      peak absorption increased initially but quickly reached a plateau that was less
      than the transport mean free path. A refractive-index-mismatched boundary between
      the ambient medium and the turbid medium deteriorated the focusing effect,
      increased the absorption near the boundary, lowered the peak absorption, and
      broadened the absorption distribution.

PMID- 18323986
TI  - Noise propagation in wave-front sensing with phase diversity.
AB  - The phase diversity technique is studied as a wave-front sensor to be implemented
      with widely extended sources. The wave-front phase expanded on the Zernike
      polynomials is estimated from a pair of images (in focus and out of focus) by use
      of a maximum-likelihood approach. The propagation of the photon noise in the
      images on the estimated phase is derived from a theoretical analysis. The
      covariance matrix of the phase estimator is calculated, and the optimal distance
      between the observation planes that minimizes the noise propagation is
      determined. The phase error is inversely proportional to the number of photons in
      the images. The noise variance on the Zernike polynomials increases with the
      order of the polynomial. These results are confirmed with both numerical and
      experimental validations. The influence of the spectral bandwidth on the phase
      estimator is also studied with simulations.

PMID- 18323987
TI  - Interferometric characterization of subwavelength lamellar gratings.
AB  - We propose a new, to our knowledge, method for determining the two main critical
      parameters of periodic one-dimensional lamellar structures, namely, linewidths
      and etched depths. The method is simple and requires only two measurements for
      the phase of the zero-transmitted order under two orthogonal polarizations. It is
      inspired by the analogy between subwavelength gratings and anisotropic
      homogeneous thin films. The method is tested with experimental data obtained with
      a Mach-Zehnder interferometer. Etched depths and linewidths derived from the
      interferograms and electromagnetic theory are compared with scanning-electron
      microscope observations.

PMID- 18323988
TI  - Experimental demonstration of a continuously variant fractional fourier
      transformer.
AB  - We demonstrate that an off-axis illuminated hemispherical-rod microlens acts as a
      fractional Fourier transformer with a continuously varying degree of
      fractionality. A complete theoretical treatment of the device as well as
      experimental results are presented.

PMID- 18323989
TI  - Hybrid holographic microscopy free of conjugate and zero-order images.
AB  - The true image area that can be used for recording microscopic objects in hybrid
      holographic microscopy can be increased by elimination of the conjugate image and
      the zero-order image. We therefore added two shutters and one phase modulator to
      the electro-optical holographic recording system so that we could change the
      recording parameters and evaluate four methods of eliminating the conjugate image
      and the zero-order image. We found that the methods that use only the phase
      modulator require the recording of fewer holograms than do the methods that use
      the shutters and also provide reconstructed images that are less noisy.

PMID- 18323990
TI  - Reconstruction of surfaces from phase-shifting speckle interferometry: Bayesian
      approach.
AB  - The reconstruction of surfaces from speckle interferometry data is a demanding
      data-analysis task that involves edge detection, edge completion, and image
      reconstruction from noisy data. We present an approach that makes optimal use of
      the experimental information to minimize the hampering influence of the noise.
      The experimental data are then analyzed with a combination of wavelet transform
      and Bayesian probability theory. Nontrivial examples are presented to illustrate
      the proposed technique.

PMID- 18323991
TI  - Encoding amplitude information onto phase-only filters.
AB  - We report a new, to our knowledge, technique for encoding amplitude information
      onto a phase-only filter with a single liquid-crystal spatial light modulator. In
      our approach we spatially modulate the phase that is encoded onto the filter and,
      consequently, spatially modify the diffraction efficiency of the filter. Light
      that is not diffracted into the first order is sent into the zero order,
      effectively allowing for amplitude modulation of either the first-order or the
      zero-order diffracted light. This technique has several applications in both
      optical pattern recognition and image processing, including amplitude modulation
      and inverse filters. Experimental results are included for the new technique.

PMID- 18323992
TI  - Comparison of automatic target recognition system performance with full- and
      reduced-resolution correlators.
AB  - The performance of an automatic target recognition (ATR) system with full- and
      reduced-resolution correlators was compared. In addition, the ATR system
      performance with reduced-resolution filter sets designed by use of
      multiresolution analyasis (MA) and downsampling (DS) techniques was also
      compared. It was discovered that results obtained at the optical correlator
      subsystem level, pertaining to the relative merits of the MA and the DS
      techniques, could not be extrapolated to the system level. This was because
      target signature differences between the test and the training imagery were
      discovered to have a greater influence on system performance than the choice of
      filter design technique. In addition, it was found that, for the case in which
      the target signature and the reduced-resolution filter were of the same size,
      there was some degradation in the receiver-operating-characteristic curve for
      reduced resolution compared with full. Nevertheless, this was deemed to have no
      practical significance, and thus the use of reduced-resolution optical
      correlators for ATR merits serious consideration.

PMID- 18323993
TI  - Phase-space measurements of micro-optical objects.
AB  - The phase-space measurement of micro-optical objects with submillimeter
      dimensions is reported for the first time to our knowledge. The experimental data
      were compared with simulated results from interferometric measurements and were
      found to be in good agreement.

PMID- 18323994
TI  - Solution to the shearing problem.
AB  - Lateral shearing interferometry is a promising reference-free measurement
      technique for optical wave-front reconstruction. The wave front under study is
      coherently superposed by a laterally sheared copy of itself, and from the
      interferogram difference measurements of the wave front are obtained. From these
      difference measurements the wave front is then reconstructed. Recently, several
      new and efficient algorithms for evaluating lateral shearing interferograms have
      been suggested. So far, however, all evaluation methods are somewhat restricted,
      e.g., assume a priori knowledge of the wave front under study, or assume small
      shears, and so on. Here a new, to our knowledge, approach for the evaluation of
      lateral shearing interferograms is presented, which is based on an extension of
      the difference measurements. This so-called natural extension allows for
      reconstruction of that part of the underlying wave front whose information is
      contained in the given difference measurements. The method is not restricted to
      small shears and allows for high lateral resolution to be achieved. Since the
      method uses discrete Fourier analysis, the reconstructions can be efficiently
      calculated. Furthermore, it is shown that, by application of the method to the
      analysis of two shearing interferograms with suitably chosen shears, exact
      reconstruction of the underlying wave front at all evaluation points is obtained
      up to an arbitrary constant. The influence of noise on the results obtained by
      this reconstruction procedure is investigated in detail, and its stability is
      shown. Finally, applications to simulated measurements are presented. The results
      demonstrate high-quality reconstructions for single shearing interferograms and
      exact reconstructions for two shearing interferograms.

PMID- 18323995
TI  - Algorithm for optimizing bipolar interconnection weights with applications in
      associative memories and multitarget classification.
AB  - An algorithm for optimizing a bipolar interconnection weight matrix with the
      Hopfield network is proposed. The effectiveness of this algorithm is demonstrated
      by computer simulation and optical implementation. In the optical implementation
      of the neural network the interconnection weights are biased to yield a
      nonnegative weight matrix. Moreover, a threshold subchannel is added so that the
      system can realize, in real time, the bipolar weighted summation in a single
      channel. Preliminary experimental results obtained from the applications in
      associative memories and multitarget classification with rotation invariance are
      shown.

PMID- 18323996
TI  - Compact parallel optical modified-signed-digit arithmetic-logic array processor
      with electron-trapping device.
AB  - A compact two-step modified-signed-digit arithmetic-logic array processor is
      proposed. When the reference digits are programmed, both addition and subtraction
      can be performed by the same binary logic operations regardless of the sign of
      the input digits. The optical implementation and experimental demonstration with
      an electron-trapping device are shown. Each digit is encoded by a single pixel,
      and no polarization is included. Any combinational logic can be easily performed
      without optoelectronic and electro-optic conversions of the intermediate results.
      The system is compact, general purpose, simple to align, and has a high signal-to
      noise ratio.

PMID- 18323997
TI  - Roles of propagating and evanescent waves in solid immersion lens systems.
AB  - The electromagnetic field incident on the thin-film layers in a solid immersion
      lens (SIL) system is decomposed into contributions from homogeneous and
      inhomogeneous waves, which are commonly referred to as propagating and evanescent
      waves, respectively. The homogeneous and the inhomogeneous parts have different
      properties with respect to the field distribution in the gap and inside the
      recording layers. The homogeneous part is shown to diffract like a focused wave
      with a numerical aperture of 1, and the inhomogeneous part decays exponentially
      away from the bottom of the SIL. Two examples are discussed in detail, and the
      concept of a vector illumination system transfer function, which includes effects
      of the recording layers, is introduced.

PMID- 18323998
TI  - Optical readout for optical storage with phase jump.
AB  - A novel, to our knowledge, optical readout for optical storage with phase jump is
      presented. In the readout scheme two coherent laser beams are focused on an
      optical disk with one beam scanning along pits and the other along land. When the
      probe beam scans across a pit, two phase jumps will take place in the
      interference resultant of the two beams if the phase difference between two beams
      is prefixed at pi, resulting in a phase pulse of 180 deg. The slopes of rising
      and falling edges of the phase pulse are infinite, and they are not affected by
      the intensity variation of the light source, stray light, and the vibration of
      the disk. Therefore this phase pulse can be used to read out the information on
      an optical disk. The use of phase jump will improve the signal-to-noise ratio of
      the readout signal and enhance the density of optical storage. An optical readout
      with phase jump was constructed. Both the theoretical design and the experimental
      verification are conducted. Experimental results show that the proposed optical
      readout is feasible.

PMID- 18323999
TI  - Theoretical study of signal-to-noise ratio on near-field photochromic memory with
      fluorescence readout.
AB  - The signal-to-noise ratio (SNR) on the fluorescence readout of a near-field
      photochromic memory was theoretically studied. Under various conditions the shot
      noise-limited SNR was analyzed. SNR by bright spot recording (BSR) that was
      better than that by dark spot recording (DSR) was obtained under the condition of
      low writing power or wide bandwidth. Under the condition of bandwidth W = 1 MHz
      and P(write) = 10(-8) W only BSR can attain sufficiently high SNR, and the SNR
      was greater by as much as 30 dB than that of DSR. It was concluded that BSR is a
      promising method for high-density near-field photochromic memory with a
      fluorescence readout.

PMID- 18324000
TI  - Self-apodization of low-resolution pixelated lenses.
AB  - We show that a pixelated lens with appropriate parameters exhibits an apodized
      point-spread function that originates in the finite size of the pixel's pupil. We
      evaluate numerically the degree of apodization and the enlargement associated
      with the point-spread function in terms of the parameters that characterize the
      pixelated lens.

PMID- 18324001
TI  - Unusual pyramidal ice in the atmosphere as the origin of elliptical halos.
AB  - The formation mechanism of elliptical halos and Bottlinger's rings has long
      remained uncertain. The current model for elliptical halos requires multiple
      scattering from two different populations of ice crystals in a complex mode of
      motion. New evidence indicates that elliptical halos, and possibly Bottlinger's
      rings, are due to refraction through ice crystals shaped like obtuse pyramids.
      This unusual ice crystal may not have been documented previously.

PMID- 18324002
TI  - Ocean inherent optical property determination from in-water light field
      measurements.
AB  - An algorithm is described and evaluated for determining the absorption and
      backscattering coefficients a(z) and bb(z) from measurements of the nadir-viewing
      radiance Lu(z) and downward irradiance Ed(z). The method, derived from radiative
      transfer theory, is similar to a previously proposed one for Eu(z) and Ed(z)and
      both methods are demonstrated with numerical simulations and field data.
      Numerical simulations and a sensitivity analysis show that good estimates of a(z)
      and bb(z) can be obtained if the assumed scattering phase function is
      approximately correct. In an experiment in Long Island Sound, estimates of a(z)
      derived with these methods agreed well with those obtained from an in situ
      reflecting tube instrument.

PMID- 18324003
TI  - Results of a monte carlo investigation of the diffuse attenuation coefficient.
AB  - There has been a large effort to relate the apparent optical properties of ocean
      water to the inherent optical properties, which are the absorption coefficient a,
      the scattering coefficient b, and the scattering phase function rho(theta). The
      diffuse attenuation coefficient kdiff' has most often been considered an apparent
      optical property. However, kdiff' can be considered a quasi-inherent property
      kdiff' when defined as a steady-state light distribution attenuation coefficient.
      The Honey-Wilson research empirically relates kdiff' to a and b. The Honey-Wilson
      relation most likely applies to a limited range of water types because it does
      not include dependence on rho(theta). A series of Monte Carlo simulations were
      initiated to calculate kdiff' in an unstratified water column. The calculations,
      which reflected open ocean water types, used ranges of the single-scattering
      albedo omega(0) and the mean forward-scattering angle theta(m) for two analytic
      phase functions with different shapes. It was found that kdiff' is nearly
      independent of the shape of rho(theta) and can be easily parameterized in terms
      of a, b, and theta(m) for 0.11 <or= theta(m) <or= 0.48 rad and 0.5 <or= omega(0)
      <or= 0.95. kdiff' is an asymptotic quantity; that is, a steady-state distribution
      is reached only after many scattering lengths.

PMID- 18324004
TI  - In situ determination of the remotely sensed reflectance and the absorption
      coefficient: closure and inversion.
AB  - We tested closure between in situ radiometric and absorption coefficient
      measurements by using a nearly backscattering-independent remote-sensing
      reflectance model that employs the remote-sensing reflectance at three
      wavelengths. We show that only a small error is introduced into the closure model
      when the proper functional relationships of f/Q and the backscattering is taken
      to be a constant when using the sea-viewing wide field-of-view sensor wavelengths
      443, 490, and 555 nm. A method of inverting the model to obtain the absorption
      coefficient by use of simple linear spectral relationships of the absorption
      coefficient is provided. The results of the model show that the independent
      measurements of reflectance and absorption obtain closure with a high degree of
      accuracy.

PMID- 18324005
TI  - Application of pulsed photoacoustics in water at high pressure.
AB  - The application of pulsed photoacoustics to the study of liquids at pressures of
      up to 350 bars is discussed. The design and development of an in-line sensor for
      the subsea monitoring of crude oil concentrations in water is reported. Crude oil
      detection sensitivities at parts per million concentrations were achieved with
      prototype instrumentation. A comparison of experimental results and a theoretical
      prediction of the pressure dependence of the pulsed photoacoustic response from
      water is outlined. The results demonstrate that existing models that describe
      pulsed photoacoustic generation in liquids are applicable to high-pressure
      conditions.

PMID- 18324006
TI  - Annealing behavior of barriers in ion-implanted LiNbO3 and LiTaO3 planar
      waveguides.
AB  - We formed planar waveguides in LiNbO(3) and LiTaO(3) crystals by megaelectron
      volt He-ion implantation. The dark modes of both waveguides are measured and
      their refractive-index profiles are described according to the parameterized
      index profile reconstruction method. The extraordinary indices of both ion
      implanted waveguides exhibit quite different profiles. We compare the thermal
      stability of barriers in ion-implanted LiNbO(3) and LiTaO(3) waveguides by
      annealing at different temperatures. The results show that the barrier in a
      LiTaO(3) planar waveguide has higher thermal stability than that in a LiNbO(3)
      waveguide. The experiments also show that annealing at a temperature higher than
      400 degrees C results in recrystallization of the barrier.

PMID- 18324007
TI  - Near band-edge field-dependent absorption coefficient and refractive index
      determined by photocurrent and transmittance measurements.
AB  - A technique is proposed for the extraction of precise values of field-dependent
      absorption coefficient alpha and refractive index n from photocurrent and
      transmittance measurements of optical modulator structures. The technique uses
      approximate results of alpha and n extracted from a simplified device as the
      initial input into an iterative procedure that utilizes the consistency between
      alpha and n to obtain successively better estimates of these parameters. The
      technique was applied to results that were measured experimentally, and we
      verified the accuracy by using synthetic data. Errors caused by measurement
      inaccuracy are also investigated. It is shown that the absorption coefficient has
      a modest sensitivity whereas the refractive index is insensitive to these errors.

PMID- 18324008
TI  - Temporal soliton switching in a rectangular nonlinear directional coupler.
AB  - We address the theory of temporal soliton switching in a planar geometry
      directional coupler constructed from silica and doped silica glass and operating
      at the central wavelength of 1.55 microm, significant for erbium-doped
      amplification. We formulate the field in the coupler in terms of the supermodes
      of the total structure and take account of the two transverse dimensions of the
      rectangular channels. In the case of the weak coupling between channels
      consistent with elimination of pulse breakup, the effect of the fields in the
      outer corner regions of the channels results in a switching intensity that
      differs significantly from that derived from coupled-mode theory on the basis of
      a slab model of the coupler.

PMID- 18324009
TI  - Passive FM laser operation and the stability of intracavity-doubled lasers.
AB  - A time-domain description of second-harmonic generation and steady-state spatial
      hole burning is used to model the performance of multimode intracavity-doubled
      lasers, avoiding some of the approximations implicit in rate equation models.
      Stable operation is predicted at the points of maximum power extraction,
      corresponding to passively locked FM laser operation, where the lack of amplitude
      modulation minimizes the nonlinear output coupling and the longitudinal-mode
      structure minimizes spatial hole burning. The laser intensity spectrum, predicted
      by this passive FM laser model, closely matches reported experimental results.

PMID- 18324010
TI  - Temperature dependence and optimization of 970-nm diode-pumped Yb:YAG and Yb:LuAG
      lasers.
AB  - We have investigated the temperature dependence of output performances for 970-nm
      diode-pumped Yb:YAG (Yb(3+):Y(3)Al(5)O(12)) and Yb:LuAG (Yb(3+):Lu(3)Al(5)O(12))
      lasers over the wide temperature range from 80 to 310 K. Temperature-optimized
      operation was experimentally demonstrated at around 160 K and was theoretically
      confirmed by taking into account the absorption spectra change of Yb crystals at
      low temperatures. Cooling the crystal to below 160 K caused a narrowing of the
      absorption bandwidth and led to a decrease in output power and efficiency.

PMID- 18324011
TI  - Mode-hop-free single-longitudinal-mode erbium-doped fiber laser frequency scanned
      with a fiber ring resonator.
AB  - We describe the experimental construction of a single-longitudinal-mode erbium
      doped fiber ring laser equipped with a ring resonator filter. The system is
      designed to avoid mode hopping and can be frequency scanned for spectroscopic
      sensor applications. We modified a conventional ring resonator filter to have the
      capability to reduce transmittance of unwanted modes, which is essential for
      frequency scanning without mode hopping.

PMID- 18324012
TI  - Simultaneous multiple-wavelength cw lasing in laser-diode-pumped composite rods
      of Nd:YAG and Nd:YLF.
AB  - Simultaneous multiple-wavelength cw laser operations were achieved in two types
      of composite laser rod composed of Nd(3+):YAG and Nd(3+):YLF crystals, which were
      laser diode (LD) pumped within a single virtual-point-source cavity. As much as
      30 W of total output at 1064- and 1047-nm wavelengths was obtained under 150-W LD
      input power, with approximately 25% from the 1047-nm wavelength. Different
      bonding methods were compared, showing that the use of an optical adhesive is
      effective and presents no deterioration at low and middle power levels.
      Simultaneous multiple-wavelength operation at 1064- and 1053-nm wavelengths was
      also studied.

PMID- 18324013
TI  - Magnetically induced nonlinear diagnostic features of fe-co-si-B metallic
      glasses.
AB  - We investigate the influence of an external magnetic field on optical
      photoinduced second-harmonic generation (PISHG) in Fe(18)Co(60)Si(9)B(13)
      metallic glass. A correlation between the output PISHG signal and degree of
      crystallinity (varied by thermoannealing) is observed. The applied magnetic field
      essentially suppresses the relaxation time of the PISHG. Strong angular
      dependence of the output PISHG signal reflects the peculiarities of phase
      synchronism conditions that exist in certain types of glass as a result of light
      scattering on grains. Saturation of the PISHG at magnetic fields higher then 0.75
      T indicates correlation between the magnetically induced ordering and
      noncentrosymmetry electron-charge density appearance. Comparison of PISHG with x
      ray diffraction results indicates that the PISHG results have higher sensitivity
      to hyperfine magnetic ordering. A possible origin of the observed phenomena is
      explained on the basis of phenomenological and microscopic approaches.

PMID- 18324014
TI  - Nonlinear optical beam propagation for optical limiting.
AB  - We implement numerical modeling of high-energy laser-pulse propagation through
      bulk nonlinear optical materials using focused beams. An executable program with
      a graphical user interface is made available to researchers for modeling the
      propagation of beams through materials much thicker than the diffraction length
      (up to 10(3) times longer). Ultrafast nonlinearities of the bound-electronic Kerr
      effect and two-photon absorption as well as time-dependent excited-state and
      thermal nonlinearities are taken into account. The hydrodynamic equations
      describing the rarefaction of the medium that is due to heating are solved to
      determine thermal index changes for nanosecond laser pulses. We also show how
      this effect can be simplified in some cases by an approximation that assumes
      instantaneous expansion (so-called thermal lensing approximation). Comparisons of
      numerical results with several Z-scan, optical limiting and beam distortion
      experiments are presented. Possible application to optimization of a passive
      optical limiter design is discussed.

PMID- 18324015
TI  - Resonant waveguide-grating switching device with nonlinear optical material.
AB  - The design and analysis of a dielectric guided-mode resonance filter (GMRF)
      utilizing a nonlinear material for the waveguide is presented. Small changes to
      the parameters of a GMRF have a large impact on its resonance. A nonlinear
      material can provide a small change in the refractive index of the waveguide,
      altering the resonance of the device and resulting in modulation of the
      transmitted and reflected output of the filter. Numerical results show that
      nonlinear switching from 100% transmission to 100% reflection can be accomplished
      with less than 100 kW/cm(2) using a simple design.

PMID- 18324016
TI  - Influence of the photomultiplier tube spatial uniformity on lidar signals.
AB  - Measurements of the spatial uniformity of Hamamatsu H5783-06 photosensor modules
      were performed by the flying spot method. The results were used to simulate the
      influence of the photomultiplier tube on a lidar signal. A simple method for
      improving the spatial uniformity is proposed.

PMID- 18324017
TI  - Noise contributions for imaging spectrometers.
AB  - In the past decade imaging spectrometers for observation of the Earth were
      developed to use the complete information of a spectrum as a major tool in the
      study of physical and biological processes of the Earth. Instead of a few
      relatively broad spectral bands (line detector), this imager concept provides for
      the detection of many contiguous narrow spectral bands by applying the technology
      of matrix detectors. The change from one-dimensional to two-dimensional solid
      state imagers makes it necessary to carry out the specific signal-to-noise ratio
      (SNR) analysis of such detectors. A simulation of maximum and minimum radiances
      for typical spectral signatures of the Earth (water, vegetation) and the
      verification of these radiances with modular optoelectronic scanner data provide
      the means for calculation of electrons generated at the matrix detector. For a
      hypothetical sensor, water-minimum and vegetation-maximum signals are calculated,
      and the degradation of the SNR caused by image smear of two-dimensional solid
      state imagers is demonstrated.

PMID- 18324018
TI  - Significance of multiple scattering from tropospheric aerosols for ground-based
      backscatter lidar measurements.
AB  - The influence of multiple scattering on the retrieval of extinction coefficients
      of tropospheric aerosols from ground-based backscatter lidar measurements is
      numerically modeled. In a first step, lidar returns are computed by means of a
      Monte Carlo code for model atmospheres with different aerosol types and different
      extinction coefficient profiles. In so doing, synthetic lidar signals with and
      without multiple scattering can be simulated. In a second step, both types of
      signal are inverted by the most frequently used analytical solution, which,
      however, is based on the single-scatter assumption. From a comparison of the
      results, the error of the retrieved aerosol-extinction profiles can be
      quantitatively determined. It was found that the contribution of multiply
      scattered photons to the lidar signals is typically below 10% and never exceeds
      20%. The relative errors of the retrieved aerosol-extinction profile in the
      planetary boundary layer are still smaller; they were determined to be less than
      3% for all aerosol types, even for extinction coefficients as large as 3.9 km(
      1). Thus, for ground-based lidar measurements and typical meteorological
      conditions, errors caused by neglecting multiple scattering are by far less
      significant than other errors in lidar data evaluation.

PMID- 18324019
TI  - Retrieval of droplet-size density distribution from multiple-field-of-view cross
      polarized lidar signals: theory and experimental validation.
AB  - Multiple-field-of-view (MFOV) secondary-polarization lidar signals are used to
      calculate the particle-size density distribution (PSD) at the base of a cloud. At
      the cloud base, multiple scattering is weak and single backscattering is
      predominant by many orders of magnitude. Because secondary polarization is a
      direct measure of multiple scattering, it is therefore advantageous to use
      secondary polarization. A mathematical relation among the PSD, the lidar fields
      of view, the scattering angles, and the angular depolarization is derived to
      facilitate use of secondary polarization. The model is supported by experimental
      MFOV lidar measurements carried out in a controlled environment, and its
      limitations and restrictions are discussed.

PMID- 18324020
TI  - Effect of the differential geometric form factor on differential absorption lidar
      measurements with topographical targets.
AB  - When the integrated differential absorption lidar (DIAL) technique is used to
      perform concentration measurements over long distances, the alignment between on
      and off laser beams becomes important. Here, through analysis of alignment error
      and of the corresponding differential geometric form factor, the effect of
      misalignment between off and on lines on performance of integrated concentration
      measurements by a coaxial DIAL system is considered.

PMID- 18324021
TI  - Influence of daylight and noise current on cloud and aerosol observations by
      spaceborne elastic scattering lidar.
AB  - The influence of daylight and noise current on cloud and aerosol observations by
      realistic spaceborne lidar was examined by computer simulations. The reflected
      solar radiations, which contaminate the daytime return signals of lidar
      operations, were strictly and explicitly estimated by accurate radiative transfer
      calculations. It was found that the model multilayer cirrus clouds and the
      boundary layer aerosols could be observed during the daytime and the nighttime
      with only a few laser shots. However, high background noise and noise current
      make it difficult to observe volcanic aerosols in middle and upper atmospheric
      layers. Optimal combinations of the laser power and receiver field of view are
      proposed to compensate for the negative influence that is due to these noises.
      For the computer simulations, we used a realistic set of lidar parameters similar
      to the Experimental Lidar in-Space Equipment of the National Space Development
      Agency of Japan.

PMID- 18324022
TI  - Size parameter for thermally emitting particles.
AB  - For thermal emission from particles the conventional size parameter X = 2 pi
      a/lambda does not distinguish between small and large particles. We show that the
      opacity parameter Omega = 4 pi ka/lambda = 2 kX is a more accurate means of
      demarcating the two emission regimes. Omega is approximately equal to the
      particle's mean optical depth, and it can be derived from both scattering theory
      and geometrical optics.

PMID- 18324023
TI  - Laboratory measurements and T-matrix calculations of the scattering matrix of
      rutile particles in water.
AB  - We present experimentally determined scattering matrix elements of birefringent
      rutile particles in water as a function of the scattering angle for a wavelength
      of 633 nm (in air). These elements are compared with the results of T-matrix
      calculations for prolate spheroids. For the diagonal matrix elements the results
      of the T-matrix calculations are in good agreement with those of the
      measurements. A good fit for the whole matrix, including the off-diagonal
      elements, is obtained when we compensate for the birefringence of the rutile
      particles by performing the computations for spheroids with a slightly larger
      length/width ratio than measured.

PMID- 18324024
TI  - Probe-beam diffraction in a pulsed top-hat beam thermal lens with a mode
      mismatched configuration.
AB  - The Fresnel diffraction integral is used directly to describe the thermal lens
      (TL) effect with a mode-mismatched collinear configuration. The TL amplitudes
      obtained with Gaussian, Airy, and top-hat beam excitations are computed and
      compared. Numerical results for beam geometries optimized for both near- and far
      field detection schemes are presented, and the analytical results developed by
      Bialkowski and Chartier [Appl. Opt. 36, 6711 (1997)] for a Gaussian beam TL
      effect are summarized in simplified form. Both the numerical and the analytical
      results demonstrate that, under a beam geometry optimized for either near- or far
      field detection, the Gaussian beam TL experiment has approximately the same
      maximum signal amplitude as does the photothermal-interference scheme. A
      comparison between the optimum near- and far-field detection beam geometries
      indicates that a practical mode-mismatched TL instrument should be based on the
      far-field detection geometry. The computation results further demonstrate that
      the optimum beam geometry and the TL amplitude depend largely on the excitation
      beam profile. The top-hat beam TL experiment is approximately twice as sensitive
      as the Gaussian beam TL scheme.

PMID- 18324025
TI  - Dispersion-free transient-grating frequency-resolved optical gating.
AB  - We have developed a compact dispersion-free TG (transient-grating) FROG
      (frequency-resolved optical gating) by utilizing a mask that separates the input
      beam into three distinct beams focused into fused silica to create the FROG
      signal. Two of the beams are reflected off the same set of mirrors to ensure
      identical optical paths, eliminating the difficulty in establishing zero time
      delay between the beams. In addition, the use of only reflective optics avoids
      material dispersion in the FROG except for the mixing crystal. This TG FROG is
      capable of operating with an intensity of 1 x 10(11) W/cm(2) and has resolutions
      less than 0.5 and 1.3 fs for 25- and 10-fs input pulses, respectively.

PMID- 18324027
TI  - Measurement of the degree of salinity of water with a fiber-optic sensor.
AB  - A fiber-optic sensor based on surface-plasmon resonance for the determination of
      the refractive index is used for measuring the degree of salinity of water. The
      transducing element consists of a multilayer structure deposited on a side
      polished monomode optical fiber. Measuring the attenuation of the power
      transmitted by the fiber shows that a linear relation with the refractive index
      of the outer medium of the structure is obtained. The system is characterized by
      use of a varying refractive index obtained with a mixture of water and ethylene
      glycol. Experimental results show that the sensor can be used as a salinity
      degree measurement device with environmental applications.

PMID- 18324028
TI  - Evaluation of the modal structure of light beams composed of incoherent mixtures
      of Hermite-Gaussian modes.
AB  - A new, to our knowledge, technique for determining the modal content of partially
      coherent beams that are made up of an incoherent superposition of Hermite
      Gaussian modes is studied. The algorithm makes use of the intensity profile of
      the beam at an arbitrarily chosen transverse plane. Analytical derivations are
      presented for a Gaussian Schell-model source and flat-topped beams, as well as an
      analysis of their performances in the presence of experimental errors and noise.
      Numerical simulations are performed to test the accuracy and the stability of the
      recovery algorithm.

PMID- 18324029
TI  - Confined blue iridescence by a diffracting microstructure: an optical
      investigation of the Cynandra opis butterfly.
AB  - When illuminated and viewed along certain well-defined directions, segments on
      the wings of the butterfly Cynandra opis shows a striking violet-blue to blue
      green. We quantify the spectral and the directional properties of these areas of
      the wings of the insect. Electron microscopy shows that wing scales from these
      iridescent regions of the wings contain two gratinglike microstructures crossed
      at right angles. Application of the diffraction theory, as formulated by the
      Stratton-Silver-Chu integral, to the microstructure can explain all the important
      features observed experimentally.

PMID- 18324030
TI  - Performance analysis of a time-division-multiplexed fiber-optic gas-sensor array
      by wavelength modulation of a distributed-feedback laser.
AB  - The results of an investigation of the performance of a time-division-addressed
      fiber-optic gas-sensor array by means of wavelength modulation of a distributed
      feedback (DFB) laser are reported. The system performance is found to be severely
      limited by the extinction ratio of the optical switch used for pulse amplitude
      modulation. Formulas that relate the cross-talk level to the extinction ratio of
      the switch, the modulation parameters of the DFB laser, and the optical path
      differences among sensing channels are derived. Computer simulation shows that an
      array of 20 methane gas sensors with a detection sensitivity of 2000 parts in
      10(6) (ppm) (10-cm gas cell) for each sensor may be realized with a commercially
      available single Mach-Zehnder amplitude modulator (-35-dB extinction ratio). An
      array of 100 sensors with a 100-ppm detection sensitivity for each sensor may be
      realized if a double Mach-Zehnder amplitude modulator is used.

PMID- 18324031
TI  - Micromachined optical fiber current sensor.
AB  - We describe a micromachined optical fiber current sensor. The sensing element
      consists of a squared silicon membrane (8 mm long and 20 microm thick) that has a
      cylindrical permanent magnet (NdFeB alloy, 3-mm diameter, 1.5 mm high) fixed on
      its central region. This structure allows the permanent magnet to vibrate in the
      presence of the magnetic field gradient generated by an ac. A linear relation
      between the electrical current and the magnet displacement was measured with
      white-light interferometry with an optical fiber low-finesse Fabry-Perot
      microcavity. A measurement range of 0-70 A and a minimum detectable intensity of
      20 mA were obtained when distance D between the membrane and the electrical power
      line was 5 mm. The output signal directly shows a linear response with distance
      D.

PMID- 18324032
TI  - Demonstration of a high-temperature fiber-optic gas sensor made with a sol-gel
      process to incorporate a fluorescent indicator.
AB  - To make a gas sensor suitable for use at high temperatures, we have used a sol
      gel-processing technique to bond a copper-exchanged zeolite fluorescence
      indicator onto the end of an all-silica optical fiber. Experimental results from
      single-fiber prototype sensors show they can be used to measure either the oxygen
      concentration or the equivalence ratio for gas mixtures containing weak or strong
      reductants, respectively.

PMID- 18324033
TI  - Straightness measurements by use of a reflection confocal optical system.
AB  - Straightness measurement is a very important technique in the field of mechanical
      engineering. A particular application for straightness measurement is high
      accuracy machining on a diamond-turning lathe. We propose a novel, to our
      knowledge, optical method for measuring the straightness of motion, and its
      mathematical analysis is outlined. The technique is based on measurement of the
      lateral displacement of point images by use of reflection confocal optical
      systems. The advantages of this method are that (i) the lateral displacements in
      the direction of the two axes perpendicular to the optical axis can be measured,
      (ii) the rotation angles around all three axes can be measured, and (iii)
      reflection optical systems are more compact in length than are transmission
      optical systems.

PMID- 18324034
TI  - Ray optics calculation of the radiation forces exerted on a dielectric sphere in
      an evanescent field.
AB  - A ray optics approach was used to calculate the forces and the torque exerted on
      a dielectric sphere in the evanescent field produced by a linearly polarized
      Gaussian beam. The particle was assumed to be immersed in a dielectric fluid next
      to a solid dielectric plate with the evanescent field produced at the solid-fluid
      interface. Comparisons with calculations performed by use of more rigorous
      electromagnetic wave theory show that the ray optics results agree to within a
      factor of 2 even for particle radii as small as twice the incident wavelength.
      Calculation of the forces for conditions typical of a total internal reflection
      microscopy experiment show that the evanescent field has a negligible effect on
      either the net forces exerted on the particle or the particle motion (i.e.,
      rotation or translation parallel to the interface). By our modifying the
      parameters of the experiment, however--namely, the incident beam power, radius of
      incident beam, and evanescent wave penetration depth--forces that are comparable
      with the net particle weight and capable of translating the particle several
      micrometers per second, as well as rotating the particle several revolutions per
      second, can be produced. The ability to micromanipulate a particle in this
      fashion could offer useful applications for studying particle and surface
      interactions.

PMID- 18324035
TI  - Two-dimensional, three-dimensional, and gray-scale images reconstructed from
      computer-generated holograms designed by use of a direct-search method.
AB  - A direct-search method for the computer design of holograms is demonstrated. Two
      dimensional, three-dimensional, and containing holograms with different levels of
      intensity (gray scales) were designed, fabricated, and optically reconstructed.
      The number of effective gray levels and the image-intensity noise and contrast
      are discussed. A modification of the state-variables cost function used in the
      direct-search algorithm that permits reliable control of gray scales is
      presented. Optical reconstructions of two-dimensional, three-dimensional, and
      gray-scale binary phase computer-generated holograms are presented.

PMID- 18324036
TI  - MASERATI: a RocketBorne tunable diode laser absorption spectrometer.
AB  - The MASERATI (middle-atmosphere spectrometric experiment on rockets for analysis
      of trace-gas influences) instrument is, to our knowledge, the first rocket-borne
      tunable diode laser absorption spectrometer that was developed for in situ
      measurements of trace gases in the middle atmosphere. Infrared absorption
      spectroscopy with lead salt diode lasers is applied to measure water vapor and
      carbon dioxide in the altitude range from 50 to 90 km and 120 km, respectively.
      The laser beams are directed into an open multiple-pass absorption setup (total
      path length 31.7 m) that is mounted on top of a sounding rocket and that is
      directly exposed to ambient air. The two species are sampled alternately with a
      sampling time of 7.37 ms, each corresponding to an altitude resolution of
      approximately 15 m. Frequency-modulation and lock-in techniques are used to
      achieve high sensitivity. Tests in the laboratory have shown that the instrument
      is capable of detecting a very small relative absorbance of 10(-4)-10(-5) when
      integrating spectra for 1 s. The instrument is designed and qualified to resist
      the mechanical stress occurring during the start of a sounding rocket and to be
      operational during the cruising phase of the flight when accelerations are very
      small. Two almost identical versions of the MASERATI instrument were built and
      were launched on sounding rockets from the Andoya Rocket Range (69 degrees N) in
      northern Norway on 12 October 1997 and on 31 January 1998. The good technical
      performance of the instruments during these flights has demonstrated that
      MASERATI is indeed a new suitable tool to perform rocket-borne in situ
      measurements in the upper atmosphere.

PMID- 18324037
TI  - Aberration-free dynamic focusing with a multichannel micromachined membrane
      deformable mirror.
AB  - We demonstrate aberration-free dynamic focusing with a low-cost 19-channel
      continuous-surface micromachined membrane deformable mirror (MMDM). A lookup
      table of the optimum control voltages for various focal lengths is obtained with
      an adaptive optics algorithm. Diffraction-limited imaging resolution is achieved
      owing to the capability of the MMDM for aberration compensation. The measured
      speed of the MMDM supports dynamic focusing operations at several hundred hertz.
      Our dynamic focusing approach is shown to function with either monochromatic or
      broadband optical sources.

PMID- 18324038
TI  - Interferometric chromatic dispersion measurements of long, gradient-index rod
      lenses in the visible and the near infrared.
AB  - A new procedure is presented for testing long, radial-gradient-index rod lenses
      in a phase-stepping Twyman-Green interferometer. In addition, a method for
      converting the measured optical phase data to the rod's index of refraction
      profile is reviewed. This procedure was used to measure refractive-index profile
      dispersions over the wavelength range of 441 to 1064 nm. These measurements
      provide the first data for refractive-index profiles of rod lenses in the
      infrared and show the existence of positive dispersion, negative dispersion, and
      near-infrared dispersion reversal in some samples. The dispersion results suggest
      the need for modifications to the current glass model.

PMID- 18324039
TI  - Self-interference patterns and their application to inertial-fusion target
      characterization.
AB  - The sphericity and wall-thickness uniformity requirements of direct-drive
      inertial-fusion targets are of the order of less than 1%. These shells display
      self-interference patterns (SIP's) when irradiated with a spatially incoherent,
      narrow-bandwidth light source and viewed with a compound microscope. These
      patterns are distinct concentric fringes when the target is uniform, whereas
      faint, distorted, or discontinuous fringes indicate a nonuniform target. We
      determined the wall thickness to within +/-0.5 microm by counting the number of
      fringes in the SIP, independent of the outside diameter. Thickness uniformity is
      verified to an accuracy better than 0.05 microm. The wall thickness of gas-filled
      targets can be determined to this accuracy without knowledge of the type of gas
      or its pressure. The SIP fringe technique is used to select polymer shells
      typically of 800- to 1000-microm diameter and 5- to 12-microm wall thickness. The
      fringe locations have been modeled by use of ray tracing and agree well with
      actual measurements of well-characterized shells. Details of the formation of the
      SIP fringes, a theoretical model, and the method used for quantitative
      measurement of the shell-wall thickness with the SIP are presented with
      validation examples.

PMID- 18324040
TI  - Simultaneous distributed strain and temperature measurement.
AB  - Brillouin-scattering-based sensors are capable of measuring either the strain or
      the temperature along the length of an optical fiber in a distributed fashion
      through measurement of the Brillouin-frequency shift. The cross sensitivity of
      the frequency shift to these two parameters makes it impossible to differentiate
      between them by measurement of the frequency shift alone. We report on a new
      technique that permits the simultaneous measurement of strain and temperature to
      resolutions of +/-178 microepsilon and +/-3.9 degrees C at a spatial resolution
      of 3.5 m by incorporation of the Brillouin-loss peak power with the conventional
      Brillouin-frequency measurement.

PMID- 18324041
TI  - Optical contamination screening of materials with a high-finesse Fabry-Perot
      cavity resonated continuously at 1.06- microm wavelength in vacuum.
AB  - An optical-loss measurement system based on a resonant Fabry-Perot cavity at 1.06
      microm in vacuum has been developed for independent monitoring of the cavity
      total loss and the optical absorption loss. Maintenance of cavity resonance over
      a one-month period allows the assessment of long-term degradation of the cavity
      optics in the presence of outgassing materials, with sensitivities of 5 ppm/yr
      for total cavity loss and 2 ppm/yr for cavity absorption loss. Test results for
      light-emitting diodes, Kapton-insulated cable assemblies, and Vac-seal epoxy
      adhesive are given. Scaling of these results to the optical performance
      requirements of LIGO is discussed.

PMID- 18324042
TI  - Direct determination of isochromatic fringe order by use of two wavelengths.
AB  - A method of direct determination of photoelastic fringe order is proposed. The
      relations between the integral fringe order for one wavelength and the fractional
      fringe orders of two wavelengths are derived. The exact fringe order of the whole
      field is automatically calculated. The usefulness of this method is demonstrated
      through experimental result.

PMID- 18324043
TI  - Error analysis of null ellipsometry with depolarization.
AB  - Null ellipsometry is analyzed for components with depolarizations for unpolarized
      incident light. Serious imperfections include sample depolarization D < 0.2,
      misalignment (deltaC < 2 degrees) and off-quarter-wave retardance (deltatau < 5
      degrees) of the compensator. The four-zone null positions are derived
      analytically to the second order of serious imperfections and are also simulated
      based on Mueller matrices with depolarization. Errors of all four-zone nulls
      increase with increasing D. Depolarizations of all components except the analyzer
      cause errors to the nulls. The errors associated with D always couple with the
      second order of deltaC and deltatau and are enhanced by csc(2) 2psi. These
      divergent errors limit the applicable region of null ellipsometry where the
      errors in psi and D are within 0.1 degrees, and the simulation agrees well with
      the analytic solutions.

PMID- 18324044
TI  - Conoscopic interferometry of surface-acoustic-wave substrate crystals.
AB  - Conoscopic interferometry is applied for determining the crystal orientation of
      lithium niobate and other commonly employed substrate wafers for integrated-optic
      and surface-acoustic-wave devices. The method is particularly applicable for
      detecting the orientation of the optic axes of the strongly birefringent niobate
      but is less sensitive for lithium tantalate or quartz. Conoscopic interference is
      a low-cost and easy-to-use method that is especially suitable for laboratory
      usage.

PMID- 18324045
TI  - Digital speckle-pattern interferometry: fringe retrieval for large in-plane
      deformations with digital speckle photography.
AB  - The compensation of large in-plane motions in digital speckle-pattern
      interferometry (DSPI) with the use of digital speckle photography (DSP) is
      demonstrated. Ordinary recordings of DSPI are recombined and analyzed with DSP.
      The DSP result is used to compensate for the bulk speckle motion prior to
      calculation of the phase map. This results in a high fringe contrast even for
      deformations of several speckle diameters. In addition, for the case of an in
      plane deformation, it is shown that the absolute phase change in each pixel may
      be unwrapped by use of the DSP result as an initial guess. The principles of this
      method and experiments showing the in-plane rotation of a plate and the encounter
      of two rounded plates are presented.

PMID- 18324046
TI  - Highly repetitive, extreme-ultraviolet radiation source based on a gas-discharge
      plasma.
AB  - An extreme-ultraviolet (EUV) radiation source near the 13-nm wavelength generated
      in a small (1.1 J) pinch plasma is presented. The ignition of the plasma occurs
      in a pseudosparklike electrode geometry, which allows for omitting a switch
      between the storage capacity and the electrode system and for low inductive
      coupling of the electrically stored energy to the plasma. Thus energies of only a
      few joules are sufficient to create current pulses in the range of several
      kiloamperes, which lead to a compression and a heating of the plasmas to electron
      densities of more than 10(17) cm(-3) and temperatures of several tens of electron
      volts, which is necessary for emission in the EUV range. As an example, the
      emission spectrum of an oxygen plasma in the 11-18-nm range is presented.
      Transitions of beryllium- and lithium-like oxygen ions can be identified. Current
      waveform and time-resolved measurements of the EUV emission are discussed. In
      initial experiments a repetitive operation at nearly 0.2 kHz could be
      demonstrated. Additionally, the broadband emission of a xenon plasma generated in
      a 2.2-J discharge is presented.

PMID- 18324047
TI  - Direct laser writing of surface reliefs in dry, self-developing photopolymer
      films.
AB  - Fabrication of surface reliefs is achieved by raster scanning dry photopolymer
      films under a focused laser beam. The formation of the structure takes place
      subsequent to illumination without any chemical treatment or wet processing.
      Computer-generated optical elements can be recorded quickly, easily, and at low
      cost. The technology is particularly well suited for rapid prototyping and design
      purposes. These photopolymer films have potential in photonics applications, such
      as diffractive optical elements and waveguide structures.

PMID- 18324048
TI  - Polychromatic reflectance and transmittance of a slab with a randomly rough
      boundary.
AB  - We investigated four different approximation models for describing the
      polychromatic reflectance and transmittance of a slab with a randomly rough
      boundary while taking into account the coherent and the incoherent scattering of
      the rough boundary. Comparisons with experiments (an etched-silicon wafer) show
      that approximation models that apply a two-scale roughness to the randomly rough
      boundary and that take into account the coherent and the incoherent scattering
      yield better agreement and extend the range of validity of the approximation to
      shorter wavelengths.

PMID- 18324049
TI  - Modulation transfer function of translucent rough sheets.
AB  - Rough surfaces in translucent protective sheets are used in imaging systems, such
      as displays, to decrease specular reflections of external sources. However, they
      modify the quality of the images formed by transmission. Using a geometric
      approximation, we have modeled the behavior of rough surfaces in imaging systems.
      This model provides an analytical expression for the modulation transfer function
      of rough surfaces.

PMID- 18324050
TI  - Efficient analysis of temporal broadening of a pulsed focused Gaussian beam in
      scattering media.
AB  - We show that the temporal broadening of a pulsed, tightly focused TEM(00) beam
      propagating in a scattering medium can be accurately modeled as a convolution
      between the initial pulse profile and an effective impulse response that is given
      by the propagation behavior of an infinitely thin pulse in the said medium. The
      impulse response is obtained with a Monte Carlo (MC) analysis of the propagating
      photons in the impulse. Our algorithm is 2 orders of magnitude less complex than
      the full MC solution of the pulse propagation problem. The accuracies, however,
      are comparable even for scattering path lengths that are 20 times the mean free
      path.

PMID- 18324051
TI  - Instrument line shape of fourier transform spectrometers: analytic solutions for
      nonuniformly illuminated off-axis detectors.
AB  - A simple and powerful method for obtaining analytic instrument line shapes
      (ILS's) for Fourier transform spectrometers is explained. ILS's for off-axis
      circular and rectangular detectors are calculated to illustrate the method.
      Results match earlier ILS simulations. The contribution of the nonuniformity of
      light intensity across the detector surface is also taken into account.

PMID- 18324052
TI  - Variation of band-edge position with errors in the monitoring of layer
      termination level for long- and short-wave pass filters.
AB  - Optical monitoring of periodic thin-film stacks by the termination of each layer
      at the same constant photometric level has certain advantages. One of these
      principal advantages is the error compensation effect in the vicinity of the
      monitoring wavelength. In this study, we examine, by simulation, the effect of an
      error in the knowledge of the absolute value of the photometric termination level
      on the probable stability in the manufacture of the edge position of a blocked
      band. The results include equations that allow the determination of the
      appropriate values of parameters associated with the optimum termination levels
      to minimize the effects of such errors.

PMID- 18324053
TI  - Ion-assisted codeposition of CaF2-rich CaF2-TiO2 composites as infrared
      transmitting films.
AB  - The influence of the TiO(2) concentration (<or=10 at. %) on the structural and
      the optical properties of CaF(2)-rich CaF(2)-TiO(2) composite films fabricated by
      reactive ion-assisted codeposition are investigated. The composition-dependent
      properties are found to be similar to those reported for composite films with
      higher TiO(2) concentrations. The surface roughness of CaF(2) films and their
      adhesion to a glass substrate are greatly improved by the addition of a small
      amount of TiO(2). These composite films are quite suitable for IR coatings as a
      transparent, low-refractive-index material at wavelengths of <10 microm. Two
      examples, a Fabry-Perot filter and a mid-IR dichroic filter, of applications that
      use CaF(2)-TiO(2) with 10-at. % TiO(2) and Ge as low- and high-refractive-index
      coating materials, respectively, are presented.

PMID- 18324054
TI  - Thin-film luminescence under ultraviolet irradiation.
AB  - The features of visible dielectric thin-film luminescence under UV irradiation
      are discussed for single layers with a particular high-index/low-index couple,
      HfO(2)/SiO(2). We exploit those results in an attempt to understand the proper
      luminescence of three different mirror stacks in terms of both luminescence
      efficiency and angular emission.

PMID- 18324055
TI  - Omnidirectional mirror design with quarter-wave dielectric stacks.
AB  - Quarter-wave stacks may be designed to reflect both polarizations of a specific
      wavelength band at all angles of incidences (omnidirectional). Expressions are
      given for both the omnidirectional band center wavelength and the bandwidth for
      selected values of the low- and the high-refractive-index layer values. It is
      shown that selecting the low refractive index near 1.45 maximizes the
      omnidirectional bandwidth for any value of the high refractive index. It is also
      shown that the omnidirectional bandwidth may be extended by addition of
      contiguous quarter-wave stacks.

PMID- 18324056
TI  - Improvements in the accuracy and the repeatability of long trace profiler
      measurements.
AB  - Modifications of the long trace profiler at the Advanced Photon Source at Argonne
      National Laboratory have significantly improved its accuracy and repeatability
      for measuring the figure of large flat and long-radius mirrors. Use of a Dove
      prism in the reference beam path corrects phasing problems between mechanical
      errors and thermally induced system errors. A single reference correction now
      completely removes both of these error signals from the measured surface profile.
      The addition of a precision air conditioner keeps the temperature in the
      metrology enclosure constant to within +/-0.1 degrees C over a 24-h period and
      has significantly improved the stability and the repeatability of the
      measurements. Long-radius surface curvatures can now be measured absolutely with
      a high degree of confidence. These improved capabilities are illustrated with a
      series of measurements of a 500-mm-long mirror with a 5-km radius of curvature.
      The standard deviation in the average of ten slope profile scans is 0.3 microrad,
      and the corresponding standard deviation in the height error is 4.6 nm.

PMID- 18324057
TI  - Spectroscopic diffuse optical tomography for the quantitative assessment of
      hemoglobin concentration and oxygen saturation in breast tissue.
AB  - Near-infrared (NIR) spectroscopic diffuse tomography has been used to map the
      hemoglobin concentration and the hemoglobin oxygen saturation quantitatively in
      tissuelike phantoms and to determine average values in vivo. A series of phantom
      calibrations were performed to achieve quantitatively accurate images of the
      absorption and the reduced scattering coefficients at multiple optical
      wavelengths. A least-squares fit was applied to absorption-coefficient images at
      multiple NIR wavelengths to obtain hemoglobin images of the concentration and the
      hemoglobin oxygen saturation. Objects of varying hemoglobin concentration and
      oxygen saturation within highly scattering media were localized and imaged to
      within 15% of their actual values. The average hemoglobin concentration and
      oxygen saturation of breast tissue was measured in vivo for two women volunteers.
      The potential application for the diagnosis of breast tumors is discussed.

PMID- 18324058
TI  - Concentration measurements of multiple analytes in human sera by near-infrared
      laser Raman spectroscopy.
AB  - Our primary goal in this study is to demonstrate that near-infrared Raman
      spectroscopy is feasible as a rapid and reagentless analytic method for clinical
      diagnostics. Raman spectra were collected on human sera by use of a 785-nm
      excitation laser and a single-stage holographic spectrometer. A partial-least
      squares method was used to predict the analyte concentrations of interest. The
      prediction errors of total protein, albumin, triglyceride, and glucose in human
      sera ranged from 1.0% to 10%, which are highly acceptable for clinical diagnosis,
      of their mean physiological levels. For investigating the potential application
      of near-infrared Raman spectroscopy in screening of therapeutical drugs and
      substances of abuse the concentrations of acetaminophen, ethanol, and codeine in
      water solution were measured in the same fashion. The errors of the Raman tests
      for acetaminophen and ethanol are lower than their toxic levels in human serum,
      and the sensitivity for detection of codeine fails to reach its toxic level.

PMID- 18324059
TI  - Scattering of he-ne laser light by an average-sized red blood cell.
AB  - The scattering of He-Ne laser light by an average-sized human red blood cell
      (RBC) is investigated numerically. The RBC is modeled as an axisymmetric, low
      contrast dielectric, biconcave disk. The interaction problem is treated
      numerically by means of a boundary-element methodology. The differential
      scattering cross sections (DSCS's) corresponding to various cell orientations are
      calculated. The numerical results obtained for the exact RBC geometry are
      compared with those corresponding to a scattering problem in which the cell is
      assumed to be either a volume-equivalent sphere or an oblate spheroid. A
      parametric study demonstrating the dependence of the DSCS on the wavelength of
      the incident wave and the cell's refractive index is presented.

PMID- 18324060
TI  - Precise, controlled laser delivery with evanescent optical waves.
AB  - Precise laser surgery is possible with laser pulses at wavelengths that are
      strongly absorbed at the surface of tissue. However, pulses at these wavelengths
      (far UV, far infrared) are not compatible with fiber-optic transmission, making
      endoscopic surgical procedures inside the body difficult. We use evanescent
      optical waves to demonstrate an alternative for confining energy near the tissue
      surface. Precise, superficial tissue ablation is achieved with evanescent waves
      generated at a sapphire-tissue interface by a free-electron laser, where the
      ablation depth may be varied. A new class of precise, controlled laser surgical
      tools may be achieved in this novel approach for use in endoscopic procedures.
      Electromagnetic theory governing evanescent-wave tissue ablation is presented.

PMID- 18324061
TI  - Analytic approach for optimal quantization of diffractive optical elements.
AB  - One of the most important factors that limit the performance of diffractive
      optical elements (DOE's) is the depth accuracy of the relief structure. A common
      procedure for fabricating DOE's is the binary optics procedure, in which binary
      masks are used for the fabrication of a multilevel relief structure. Here an
      analytic procedure for calculating the optimal depth levels of DOE's, the phase
      bias, and the decision levels is presented. This approach is based on the
      minimization of the mean-squared error caused by the quantization of the
      continuous profile. As a result of the minimization an optimal value for the
      etching depth of each photolithographic mask is determined. The obtained depth
      values are, in general, different from the depth values used by the conventional
      multilevel approach. Comprehensive mathematical analysis is given, followed by
      several computer simulations that demonstrate the advantages of the proposed
      procedure.

PMID- 18324062
TI  - High-rate-long-distance fiber-optic communication based on advanced modulation
      techniques.
AB  - The presence of fiber attenuation and chromatic dispersion is one of the major
      design aspects of fiber-optic communication systems when one addresses high-rate
      and long-distance digital data transmission. Conventional digital communication
      systems implement a modulation technique that generates light pulses at the fiber
      input end and tries to detect them at the fiber output end. Here an advanced
      modulation transmission system is developed based on knowledge of the exact
      dispersion parameters of the fiber and the principles of space-time mathematical
      analogy. The information encodes the phase of the input light beam (a continuous
      laser beam). This phase is designed such that, when the signal is transmitted
      through a fiber with a given chromatic dispersion, high peak pulses emerge at the
      output, which follows a desired bit pattern. Thus the continuous input energy is
      concentrated into short time intervals in which the information needs to be
      represented at the output. The proposed method provides a high rate-distance
      product even for fibers with high dispersion parameters, high power at the
      output, and also unique protection properties. Theoretical analysis of the
      proposed method, computer simulations, and some design aspects are given.

PMID- 18324063
TI  - Continuous-scale-invariant pattern recognition with adaptive-wavelet-matched
      filters.
AB  - We designed and implemented a composite-wavelet-matched filter that is invariant
      to continuous-scale changes of the input and is useful for correlation-based
      pattern recognition of objects whose size is not known exactly. We optimize the
      adaptive wavelet to extract sparse image features and use the scale-space
      analysis to determine the wavelet scale for the scale invariance. Experimental
      results obtained by use of a programmable optical correlator with three liquid
      crystal spatial light modulators are demonstrated.

PMID- 18324064
TI  - Diffraction efficiency and signal-to-noise ratio of diffuse-object holograms in
      real time in polyvinyl alcohol photopolymers.
AB  - We studied the influence of the beam ratio and intensity on the optical quality
      of the transmission hologram images of diffuse objects stored in a photopolymer
      and reconstructed in real time. The signal-to-noise ratio and the diffraction
      efficiency were used as measures of the optical quality. We obtained a signal-to
      noise ratio of 0.94 with a diffraction efficiency of 13% for a beam ratio of 20
      and an intensity of 1.2 mW/cm2.

PMID- 18324065
TI  - Diffraction properties of transmission photorefractive volume gratings in a
      cerium-doped potassium sodium strontium barium niobate crystal.
AB  - The diffraction efficiency of volume gratings written by two-wave mixing in a
      cerium-doped potassium sodium strontium barium niobate (Ce:KNSBN) photorefractive
      crystal is studied. It is found that the diffraction efficiency strongly depends
      on the polarization of writing beams and exhibits loop behavior with respect to
      the fringe modulation. The fringe modulations before and behind the crystal are
      compared. Modified coupled-wave theory is used to fit the experimental data. This
      research presents data that are relevant to the application of Ce:KNSBN crystals
      to holographic recording and optical information processing.

PMID- 18324066
TI  - Phase-shifting joint transform correlation with phase-iterative algorithm: effect
      of the dynamic range limit.
AB  - With phase-shifting joint transform correlation (PSJTC) one uses multiple phase
      shifts to recover the phase difference between Fourier transforms of the input
      and the reference. In PSJTC systems the resulting phase-only function is used
      instead of the joint transform power spectrum (JTPS). Provided it can be recorded
      linearly, the JTPS reduces to a modulated sinusoidal fringe, especially when the
      target image matches the reference image. In practice, the JTPS has a wide
      dynamic range, and a CCD camera has a nonlinear response. Correspondingly, the
      recorded JTPS turns out to be different from a perfect sinusoidal fringe. Here we
      study the dynamic range effects of realizing PSJTC with the phase-iterative
      algorithm.

PMID- 18324067
TI  - Image compression in signal-dependent noise.
AB  - The performance of an image compression scheme is affected by the presence of
      noise, and the achievable compression may be reduced significantly. We
      investigated the effects of specific signal-dependent-noise (SDN) sources, such
      as film-grain and speckle noise, on image compression, using JPEG (Joint
      Photographic Experts Group) standard image compression. For the improvement of
      compression ratios noisy images are preprocessed for noise suppression before
      compression is applied. Two approaches are employed for noise suppression. In one
      approach an estimator designed specifically for the SDN model is used. In an
      alternate approach, the noise is first transformed into signal-independent noise
      (SIN) and then an estimator designed for SIN is employed. The performances of
      these two schemes are compared. The compression results achieved for noiseless,
      noisy, and restored images are also presented.

PMID- 18324068
TI  - Reconstruction of an object from its noisy Fourier modulus: ideal estimate of the
      object to be reconstructed and a method that attempts to find that estimate.
AB  - In general, the problem of reconstructing an object from its Fourier modulus has
      no solution when the Fourier modulus is contaminated by noise. Therefore a quasi
      solution, which we call the ideal estimate of the object to be reconstructed, is
      defined here based on the concept of territories of the convergence objects of
      the error-reduction algorithm, and a method that attempts to find that solution
      is presented. Keeping in mind that the ideal estimate is one of the output
      stagnation objects of the hybrid input-output algorithm, we modify the hybrid
      input-output algorithm so that the output-stagnation objects can be located even
      when the value of the feedback parameter is not infinitesimally small, and this
      modified algorithm is combined with the hybrid input-output algorithm itself. The
      results of computer simulations carried out to test the performance of the
      proposed method are shown.

PMID- 18324069
TI  - Phase unwrapping with the branch-cut method: clustering of discontinuity sources
      and reverse simulated annealing.
AB  - The branch-cut method is a powerful tool for correct unwrapping of phase maps in
      optical metrology. However, this method encounters the problem of the correct
      setting of the cuts, which belongs to the class of nondeterministic-polynomial
      time-complete problems. Simulated annealing is an algorithm used to solve
      problems of this kind in a polynomial-time execution. However, the algorithm
      still requires an enormous calculation time if the number of discontinuity
      sources and thus the number of branch cuts is high. We illustrate the motivation
      for the use of this algorithm and show how the running time can be severely
      reduced by use of reverse simulated annealing, starting from the nearest-neighbor
      solution to find a proper initial configuration, and by clustering of
      discontinuity sources.

PMID- 18324070
TI  - Multiwavelength optical content-addressable parallel processor for high-speed
      parallel relational database processing.
AB  - We present a novel, to our knowledge, architecture for parallel database
      processing called the multiwavelength optical content-addressable parallel
      processor (MW-OCAPP). The MW-OCAPP is designed to provide efficient parallel data
      retrieval and processing by means of moving the bulk of database operations from
      electronics to optics. It combines a parallel model of computation with the many
      degrees-of-processing freedom that light provides. The MW-OCAPP uses a
      polarization and wavelength-encoding scheme to achieve a high level of
      parallelism. Distinctive features of the proposed architecture include (1) the
      use of a multiwavelength encoding scheme to enhance processing parallelism, (2)
      multicomparand word-parallel bit-parallel equality and magnitude comparison with
      an execution time independent of the data size or the word size, (3) the
      implementation of a suite of 11 database primitives, and (4) multicomparand two
      dimensional data processing. The MW-OCAPP architecture realizes 11 relational
      database primitives: difference, intersection, union, conditional selection,
      maximum, minimum, join, product, projection, division, and update. Most of these
      operations execute in constant time, independent of the data size. We outline the
      architectural concepts and motivation behind the MW-OCAPP's design and describe
      the architecture required for implementing the equality and intersection
      difference processing cores. Additionally, a physical demonstration of the
      multiwavelength equality operation is presented, and a performance analysis of
      the proposed system is provided.

PMID- 18324071
TI  - Logic-operated mathematical morphology and its optical implementation.
AB  - A more powerful tool for binary image processing, i.e., logic-operated
      mathematical morphology (LOMM), is proposed. With LOMM the image and the
      structuring element (SE) are treated as binary logical variables, and the
      MULTIPLY between the image and the SE in correlation is replaced with 16 logical
      operations. A total of 12 LOMM operations are obtained. The optical
      implementation of LOMM is described. The application of LOMM and its experimental
      results are also presented.

PMID- 18324072
TI  - Estimation of insertion loss of a holographic switch with an optically addressed
      spatial light modulator.
AB  - We investigate the cause of the insertion loss of our holographic switch by
      determining the relation between the diffraction efficiency and the hologram
      patterns generated by the control beams. According to the calculation the
      theoretical insertion loss is 7.4 dB with loss distribution of 0.03 dB under the
      conditions of a previous experiment. We find that incomplete storage of the
      interference pattern on the optically addressed spatial light modulator is the
      strongest factor determining the insertion loss.

PMID- 18324073
TI  - Two-step digit-set-restricted modified signed-digit addition-subtraction
      algorithm and its optoelectronic implementation.
AB  - A novel, to our knowledge, two-step digit-set-restricted modified signed-digit
      (MSD) addition-subtraction algorithm is proposed. With the introduction of the
      reference digits, the operand words are mapped into an intermediate carry word
      with all digits restricted to the set {1, 0} and an intermediate sum word with
      all digits restricted to the set {0, 1}, which can be summed to form the final
      result without carry generation. The operation can be performed in parallel by
      use of binary logic. An optical system that utilizes an electron-trapping device
      is suggested for accomplishing the required binary logic operations. By
      programming of the illumination of data arrays, any complex logic operations of
      multiple variables can be realized without additional temporal latency of the
      intermediate results. This technique has a high space-bandwidth product and
      signal-to-noise ratio. The main structure can be stacked to construct a compact
      optoelectronic MSD adder-subtracter.

PMID- 18324074
TI  - Optomechanical design and characterization of a printed-circuit-board-based free
      space optical interconnect package.
AB  - We present a proof of concept and a feasibility demonstration of a practical
      packaging approach in which free-space optical interconnects (FSOI's) can be
      integrated simply on electronic multichip modules (MCM's) for intra-MCM-board
      interconnects. Our system-level packaging architecture is based on a modified
      folded 4f imaging system that has been implemented with only off-the-shelf
      optics, conventional electronic packaging, and passive-assembly techniques to
      yield a potentially low-cost and manufacturable packaging solution. The
      prototypical system as built supports 48 independent FSOI channels with 8
      separate laser and detector chips, for which each chip consists of a one
      dimensional array of 12 devices. All the chips are assembled on a single
      substrate that consists of a printed circuit board or a ceramic MCM. Optical link
      channel efficiencies of greater than 90% and interchannel cross talk of less than
      -20 dB at low frequency have been measured. The system is compact at only 10 in.3
      (25.4 cm3) and is scalable, as it can easily accommodate additional chips as well
      as two-dimensional optoelectronic device arrays for increased interconnection
      density.

PMID- 18324075
TI  - Improving holographic data storage by use of an optimized phase mask.
AB  - A method for improving the spectral distribution and for reducing the
      reconstruction error in optical holographic data storage is proposed. By use of
      an optimized phase mask in the input plane, the uniformity of the spectral
      distribution is optimized and the reconstruction error minimized. The phase mask
      is designed by use of amplitude-phase retrieval algorithms. Simulation results
      show the merits of the proposed method.

PMID- 18324076
TI  - Spatial light modulators for high-brightness projection displays.
AB  - We fabricated polymer-dispersed liquid-crystal light valves (PDLCLV's) consisting
      of a 30-microm-thick hydrogenated amorphous-silicon film and a 10-microm-thick
      polymer-dispersed liquid-crystal (PDLC) film composed of nematic liquid-crystal
      (LC) microdroplets surrounded by polymer. The device can modulate high-power
      reading light, because the PDLC becomes transparent or opalescent independent of
      the polarization state of the reading light when either sufficient or no writing
      light is incident on the PDLCLV. This device has a limiting resolution of 50
      lp/mm (lp indicates line pairs), a reading light efficiency of 60%, a ratio of
      intensity of light incident on the PDLC layer to intensity of light radiated from
      the layer, and an extinction ratio of 130:1. The optically addressed video
      projection system with three PDLCLV's, LC panels of 1048 x 480 pixels as input
      image sources, a 1-kW Xe lamp, and a schlieren optical system projected
      television (TV) pictures of 600 and 450 TV lines in the horizontal and the
      vertical directions on a screen with a diagonal length of 100 in. The total
      output flux of this system was 1500 lm.

PMID- 18324077
TI  - Diffraction light modulator based on transverse electro-optic effect in short
      pitch ferroelectric liquid crystals.
AB  - A diffraction modulator that exploits the transverse electro-optic effect in
      ferroelectric liquid crystals is proposed for applications in displays and in
      spatial light modulators. Experiments with a short-pitch ferroelectric liquid
      crystal aligned homeotropically show an achromatic contrast ratio of greater than
      100:1 available with oblique readout. The sources of the contrast deterioration
      and the tolerance of the proposed scheme to this deterioration are analyzed. For
      selected directions of readout the light output obtains low sensitivity to the
      polarization of the readout light. Nonlaser light sources can be used in a
      practical display setup based on the proposed principle.

PMID- 18324078
TI  - Site-selective hole burning in Eu3+:Y2SiO5.
AB  - We found that the Eu3+ ion occupies several distinct sites in Y2SiO5. We were
      also able to perform hole-burning studies in more than 40 different transitions.

PMID- 18324079
TI  - Fast radiative transfer model for simulation of infrared atmospheric sounding
      interferometer radiances.
AB  - A fast radiative transfer model has been developed for prelaunch simulation
      studies of Infrared Atmospheric Sounding Interferometer (IASI) data and for the
      exploitation of IASI radiances within the framework of a numerical weather
      prediction variational analysis scheme. The model uses profile-dependent
      predictors to parameterize the atmospheric optical depths and is fast enough to
      cope with the processing of observations in near real time and with the several
      thousands of transmittance calculations required to simulate radiances from a
      full range of atmospheric conditions. The development of the model has involved
      the selection of a training set of atmospheric profiles, the production of a line
      by-line transmittance database, the selection of optimal predictors for the gases
      considered in the study, and the production of regression coefficients for the
      fast transmittance scheme. The model fit to the line-by-line radiances shows that
      it can reproduce the line-by-line radiances to a degree of accuracy that is at or
      below the instrumental noise.

PMID- 18324080
TI  - Initial analysis of ocean color data from the ocean color and temperature
      scanner. II. Geometric and radiometric analysis.
AB  - We assessed the geometric and radiometric performance of the ocean color and
      temperature scanner (OCTS) using data acquired over the United States. Initial
      results indicated a geometric offset in the along-track direction of 4-5 pixels
      that was attributed to a tilt bias. OCTS radiometric data appeared to suffer from
      near-field and possibly far-field scatter effects. Analysis of radiometric
      stability was inconclusive because of daily variability and the absence of a full
      seasonal cycle. Comparison of OCTS-computed water-leaving radiances with
      colocated in situ measurements showed that the prelaunch calibration required
      adjustment from -2% to +13%. Minor modification of OCTS data processing based on
      these results and avoidance of near-field scatter effects can enable improved and
      more-reliable OCTS data for quantitative scientific analyses.

PMID- 18324081
TI  - Calculating correlated color temperatures across the entire gamut of daylight and
      skylight chromaticities.
AB  - Natural outdoor illumination daily undergoes large changes in its correlated
      color temperature (CCT), yet existing equations for calculating CCT from
      chromaticity coordinates span only part of this range. To improve both the gamut
      and accuracy of these CCT calculations, we use chromaticities calculated from our
      measurements of nearly 7000 daylight and skylight spectra to test an equation
      that accurately maps CIE 1931 chromaticities x and y into CCT. We extend the work
      of McCamy [Color Res. Appl. 12, 285-287 (1992)] by using a chromaticity epicenter
      for CCT and the inverse slope of the line that connects it to x and y. With two
      epicenters for different CCT ranges, our simple equation is accurate across wide
      chromaticity and CCT ranges (3000-10(6) K) spanned by daylight and skylight.

PMID- 18324082
TI  - Model of the diffuse reflectivity of fly ash and its application to an optical
      sensor system for the determination of carbon in fly ash.
AB  - Fly ash, a fine gray powder, is filtered out of the flue gas in coal-fired power
      stations. It consists of silicon oxide, metal oxides, and unburned carbon. An
      optical sensor system for measurement of the carbon content of fly ash is
      described. Based on a mathematical model, an algorithm is deduced that allows the
      carbon content to be calculated from two measurements of the diffuse reflectivity
      of a fly ash sample before and after a surface-grinding process. In this model
      the fly ash sample is assumed to be composed of three types of cube: light
      scattering cubes, soft absorbing cubes (carbon), and hard absorbing cubes (iron
      oxide).

PMID- 18324083
TI  - Beam misalignments and fluid velocities in laser-induced thermal acoustics.
AB  - Beam misalignments and bulk fluid velocities can influence the time history and
      intensity of laser-induced thermal acoustics (LITA) signals. A closed-form
      analytic expression for LITA signals incorporating these effects is derived,
      allowing the magnitude of beam misalignment and velocity to be inferred from the
      signal shape. It is demonstrated how instantaneous, nonintrusive, and remote
      measurement of sound speed and velocity (Mach number) can be inferred
      simultaneously from homodyne-detected LITA signals. The effects of different
      forms of beam misalignment are explored experimentally and compared with theory,
      with good agreement, allowing the amount of misalignment to be measured from the
      LITA signal. This capability could be used to correct experimental misalignments
      and account for the effects of misalignment in other LITA measurements. It is
      shown that small beam misalignments have no influence on the accuracy or
      repeatability of sound speed measurements with LITA.

PMID- 18324084
TI  - Experimental observation of longitudinal modulation of mode fields in
      periodically segmented waveguides.
AB  - We present what is to our knowledge the first experimental observation by
      fluorescent visualization, of the evolution of the mode field profile in a
      periodically segmented waveguide. The experimental observations are then compared
      with the numerical results obtained by a finite-difference beam propagation
      method. Good agreement between experimental and numerical results is observed.

PMID- 18324085
TI  - Incoupling waveguide holograms for simultaneous focusing into multiple arbitrary
      positions.
AB  - A design method is presented that enables the realization of a novel type of
      incoupling waveguide hologram (IWGH) that simultaneously focuses the incoupled
      light to any desired positions in the waveguide. IWGH's, or grating couplers, are
      gratinglike structures etched into the waveguide surface. They couple the light
      incident from free space into the waveguide. The grating lines can be dislocated
      with respect to each other to provide phase modulation of the incoupled light. By
      use of this phase modulation, novel beam splitting and focusing functions can be
      built into the IWGH's. The new design algorithm is based on a model that assumes
      a simple relation between the incident light wave and the locally excited guided
      wave. This model is used to obtain an efficient formulation of the optimization
      problem. Four different IWGH's were designed and fabricated in InP for light at
      1550-nm wavelength. Experiments confirm that these IWGH's are capable of
      incoupling the incident wave and simultaneously splitting and focusing the guided
      wave into multiple positions in the waveguide at different distances from the
      IWGH.

PMID- 18324086
TI  - Reduction of the temperature dependence of the nonreciprocal effect of magneto
      optic channel waveguides.
AB  - The nonreciprocal effect is the difference Deltabeta = beta(forward)
      beta(backward) between forward and backward-propagation constants of optical
      modes. This effect is analyzed for the fundamental TM00 mode of channel
      waveguides in epitaxially grown magnetic garnet films. To increase |Deltabeta|,
      double layers with opposite signs of Faraday rotation are used to prepare the
      waveguides. It is shown that the temperature dependence of Deltabeta can be
      reduced considerably if the layer with positive Faraday rotation, which is at
      room temperature close to the Curie point, is replaced by a paramagnetic layer
      with negligible Faraday rotation. Concurrently, however, |Deltabeta| is decreased
      by approximately 35% at 295 K.

PMID- 18324087
TI  - Power-scalable system of phase-locked single-mode diode lasers.
AB  - The direct use of diode lasers for high-power applications in material processing
      is limited to applications with relatively low beam quality and power density
      requirements. To achieve high beam quality one must use single-mode diode lasers,
      however with the drawback of relatively low optical output powers from these
      components. To realize a high-power system while conserving the high beam quality
      of the individual emitters requires coherent coupling of the emitters. Such a
      power-scalable system consisting of 19 slave lasers that are injection locked by
      one master laser has been built and investigated, with low-power diode lasers
      used for system demonstration. The optical power of the 19 injection-locked
      lasers is coupled into polarization-maintaining single-mode fibers and
      geometrically superimposed by a lens array and a focusing lens. The phase of each
      emitter is controlled by a simple electronic phase-control loop. The coherence of
      each slave laser is stabilized by computer control of the laser current and
      guarantees a stable degree of coherence of the whole system of 0.7. An
      enhancement factor of 13.2 in peak power density compared with that which was
      achievable with the incoherent superposition of the diode lasers was observed.

PMID- 18324088
TI  - Efficient operation of a diode-bar-pumped Nd:YAG laser on the low-gain 1123-nm
      line.
AB  - Efficient operation of a Nd:YAG laser on the low-gain 1123-nm transition by end
      pumping with the reshaped output from a 7-W diode bar is reported. Using a simple
      standing-wave laser configuration and pumping with 5.6 W of incident power
      yielded a laser output power of 1.7 W in a near-diffraction-limited TEM00 mode
      with a beam quality factor of M2 < or approximately equal to 1.1. A
      unidirectional single-frequency ring laser was also constructed, yielding 180 mW
      of single-frequency output. The prospects for further increase in power by
      optimization of the resonator design are discussed.

PMID- 18324089
TI  - High-power 980-nm pump laser modules for erbium-doped fiber amplifiers.
AB  - High-power fiber-coupled pump modules with an emission wavelength of 980 nm and
      output powers in excess of 200 mW, as measured at the fiber end, have been
      fabricated. Laser-to-fiber coupling efficiencies in excess of 77% are observed to
      be in excellent agreement with a mathematical model. Also, the output power
      stability of these modules has been monitored during severe temperature cycling,
      and the relative power variation was less than 4% for all the tested modules.

PMID- 18324090
TI  - Regenerative ring-laser design by use of an intracavity diffractive mode
      selecting element.
AB  - We report what we believe to be the first application of diffractive phase
      elements for transverse mode selection in laser ring resonators. We show that
      this resonator type offers several advantages over Fabry-Perot resonators with
      diffractive mirrors. The design for a regenerative ring resonator that produces
      an eighth-order super-Gaussian intensity profile beam is presented. Numerical
      simulations, including modeling of the gain saturation and experimental tests,
      have been carried out to demonstrate the performance of this approach for cw and
      pulsed operations.

PMID- 18324091
TI  - Threshold analysis of a chirped-grating distributed-feedback laser with the power
      series method.
AB  - A new and efficient method for analyzing a chirped-grating distributed-feedback
      (DFB) laser is presented. We show that coupled-wave equations can be solved by
      use of the power series method. The single-mode gain margin of a linearly chirped
      grating DFB laser is calculated for different chirping factors and coupling
      constants. We found that clearly optimum chirping exists for which the single
      mode gain margin is maximum. The gain margins were also calculated for different
      positions of the cavity center. The effect of facet reflectivities and their
      phases on the gain margin was investigated. We found that the gain margin is
      maximum and the spatial hole burning is minimum for the cavity center at the
      middle of the laser cavity.

PMID- 18324092
TI  - High-power diode-pumped AlGaAs surface-emitting laser.
AB  - We report the development and characterization of an efficient diode-pumped
      surface-emitting semiconductor laser operating at approximately 870 nm. By using
      a semiconductor Bragg reflector stack/multiple GaAs quantum well structure,
      mounted within a conventional laser cavity, we achieved single transverse mode
      laser output powers of 153 mW. Self-tuning over a 15-nm spectral range has been
      obtained.

PMID- 18324093
TI  - Spatial pattern of microchannel formation in fused silica irradiated by
      nanosecond ultraviolet pulses.
AB  - We present numerical simulations of propagation of ultraviolet pulses through
      fused silica using a model that allows for the accumulative action of compaction
      back on the light. Compaction-induced self-focusing causes the light field to
      develop into a pattern of hot spots around the incident aperture that correlates
      with the damage patterns observed during marathon experiments designed to
      determine the onset of microchannel formation.

PMID- 18324094
TI  - Third-harmonic generation imaging of laser-induced breakdown in glass.
AB  - We present the results of three-dimensional third-harmonic generation imaging of
      laser-induced breakdown in glass by focused microjoule femtosecond near-IR
      pulses. This technique has the potential to resolve three dimensionally
      microstructures that result from laser-induced breakdown. As a potential optical
      data storage approach it is shown that the same IR laser beam can be used for
      writing and, at a lower power, for reading. The induced microdamage is shown to
      be three dimensionally confined and to depend on the write power.

PMID- 18324095
TI  - Calculation of error propagation by use of total reflection geometry for
      evaluating third-order nonlinear optical materials.
AB  - The intrinsic error propagation in a technique that uses total reflection
      geometry for the measurement of chi(3) is calculated. The results show how
      accurately the parameters should be measured to obtain the chi(3) value with the
      required precision. The film thickness should be slightly less than the
      fundamental wavelength to reduce the chi(3) error that propagates from other
      parameters.

PMID- 18324096
TI  - Fabrication of photonic crystal lasers by nanomolding of solgel glasses.
AB  - We demonstrate the formation, in a single process step, of periodic arrays of
      features of surface relief with submicrometer lateral dimensions in hybrid
      organic and inorganic solgel glasses by using elastomeric molding techniques.
      Lasers formed with molded photonic crystal resonators that consist of triangular,
      square, and honeycomb lattices of cylindrical posts and holes show emission
      spectra and lasing thresholds that are similar to devices formed by conventional
      high-resolution photolithographic patterning of thick layers of thermally grown
      oxide.

PMID- 18324097
TI  - Theoretical description based on Fourier analysis of wavelength-modulation
      spectrometry in terms of analytical and background signals.
AB  - A theoretical description of the wavelength-modulation (WM) spectrometry
      technique is given. The formalism is based on Fourier analysis and can therefore
      correctly handle arbitrary large frequency-modulation amplitudes. It can also
      deal with associated intensity modulations as well as wavelength-dependent
      transmission effects. It elucidates clearly how various Fourier components of
      these entities combine with those of the line-shape function to yield separately
      the final analytical and background nf WM signals. Explicit expressions are given
      for the 2f and the 4f signals. It is shown, among other things, that the 4f
      technique in general gives rise to smaller background signals (and therefore
      larger signal-to-background ratios) than does the 2f technique when the
      background is dominated by etalon effects from short cavities and that a finite
      intensity modulation necessarily leads to an out-of-phase nf WM signal. The
      formalism is also able to elucidate clearly that a linear intensity modulation is
      not sufficient to cause any 2f background residual-amplitude-modulation signals
      (as was the general consensus until recently in the literature) but that 2f
      background signals instead can exist only in systems with either wavelength
      dependent transmission or a laser with nonlinear intensity modulation.

PMID- 18324098
TI  - Methodology for the independent calibration of Raman backscatter water-vapor
      lidar systems.
AB  - We present a method for the independent calibration of Raman backscatter water
      vapor lidar systems. Particular attention is given to the resolution of
      instrumental changes in the short and the long terms. The method reposes on the
      decomposition of the instrument function, which allows the lidar calibration
      coefficient to be re-expressed as the product of two terms, one describing the
      instrumental transmission and detection efficiency and the other describing the
      wavelength-dependent convolution of the Raman backscatter cross sections with the
      instrument function. The origins of changes in instrument response necessitate
      the experimental determination of the system detection efficiency. Two external
      light sources for calibration are assessed: zenith observation of diffuse
      sunlight and a xenon arc lamp. The results favor use of the diffuse-sunlight
      measurement but highlight the need for simultaneous sunphotometer measurements to
      constrain modeled aerosol optical properties. Quantum mechanical models of the
      Raman cross sections are described, and errors in determining the cross sections
      and their convolution with the instrument function are discussed in detail. The
      calibration coefficients deduced by using the independent method are compared
      with coefficients deduced from Vaisala H-Humicap radiosonde measurements. These
      results agree to within current calibration errors (15%, unconstrained aerosol
      parameters), and a change in calibration coefficient following instrument
      modification is reproduced satisfactorily. Results from modeling and
      intercomparison studies are extended to estimate the calibration accuracy and the
      precision of the diffuse-sunlight method with constrained modeled aerosol
      parameters. Changes in the calibration coefficient in the short and the long
      terms should be resolved to 4(6)% and 6(9)%, respectively, which is comparable or
      better than the precision of existing dependent methods of calibration. The
      reduction of the absolute calibration error remains an outstanding issue for all
      calibration methods.

PMID- 18324099
TI  - Implementation and validation of a Raman lidar measurement of middle and upper
      tropospheric water vapor.
AB  - Implementation of a Raman lidar measurement of middle and upper tropospheric
      water vapor is described for a system that uses a 532-nm exciting wavelength,
      fiber-optic signal transfer, and Q-branch selection. Particular attention is
      given to the minimization of systematic biases introduced by fluorescent
      reemission of energy associated with elastic backscatter returns. We compare
      lidar profiles with collocated radiosonde measurements by using the Vaisala H
      Humicap capacitive captor. The variations in the water-vapor concentrations on
      vertical scales of the order of 1 km in the upper troposphere observed by the two
      instruments present significant differences. Independent characterization of
      random and systematic lidar measurement errors and radiosonde sensor response
      characteristics lead to the conclusion that these differences are due to
      radiosonde sensor response. These intercomparisons indicate that the lidar
      measurement can provide important information on water-vapor distributions in the
      radiatively important 8-11-km region.

PMID- 18324100
TI  - Single and tandem Fabry-Perot etalons as solar background filters for lidar.
AB  - Atmospheric lidar is difficult in daylight because of sunlight scattered into the
      receiver field of view. In this research methods for the design and performance
      analysis of Fabry-Perot etalons as solar background filters are presented. The
      factor by which the signal to background ratio is enhanced is defined as a
      measure of the performance of the etalon as a filter. Equations for evaluating
      this parameter are presented for single-, double-, and triple-etalon filter
      systems. The role of reflective coupling between etalons is examined and shown to
      substantially reduce the contributions of the second and third etalons to the
      filter performance. Attenuators placed between the etalons can improve the filter
      performance, at modest cost to the signal transmittance. The principal parameter
      governing the performance of the etalon filters is the etalon defect finesse.
      Practical limitations on etalon plate smoothness and parallelism cause the defect
      finesse to be relatively low, especially in the ultraviolet, and this sets upper
      limits to the capability of tandem etalon filters to suppress the solar
      background at tolerable cost to the signal.

PMID- 18324101
TI  - Fabry-Perot etalon aperture requirements for direct detection Doppler wind lidar
      from Earth orbit.
AB  - The design of Fabry-Perot etalons for direct detection Doppler wind lidar from a
      satellite is considered for two direct detection methods, fringe imaging
      (multichannel) and double edge. The area solid-angle product of the etalon for
      each technique is derived and shown to be inherently larger, for a given etalon
      aperture, for the fringe imager than for the double-edge Doppler analyzer.
      Modeling of the Doppler measurement accuracy of a spaceflight direct detection
      wind lidar shows that a very large optical aperture, 2 m or more, is necessary.
      Optical throughput matching to a 2-m collector requires, for the fringe-imaging
      Doppler analyzer, an etalon with 60 mm aperture, whereas the double-edge
      technique would require two etalons of 200 mm aperture, or a split-aperture
      etalon of 400 mm working aperture. Because the two direct detection methods have
      been shown to have practically identical intrinsic sensitivities (measurement
      accuracies per unit signal), this difference in etalon dimensions may be a
      significant selection consideration.

PMID- 18324102
TI  - Laser-induced incandescence applied to metal nanostructures.
AB  - Laser-induced incandescence is both characterized and demonstrated for the
      measurement of metal nanoparticle concentration. Reported are the results of an
      initial characterization of the spectral and temporal signature of the laser
      induced incandescence as a function of the excitation laser fluence and
      wavelength. Validation of the incandescence as a measure of the concentration is
      demonstrated by absorption measurements. Fluence dependence measurements are also
      presented. Double-pulse measurements determine the fluence for the onset of
      vaporization-induced mass loss. Comparisons between the present observations and
      those for carbon nanostructures are also made. Metals tested include (in order of
      increasing vaporization temperature) Fe, Ti, Mo, and W.

PMID- 18324103
TI  - Thermal luminescence sensor for ground-path contamination detection.
AB  - A standoff method of detecting liquids on terrestrial and synthetic landscapes is
      presented. The interstitial liquid layers are identified through their unique
      molecular vibration modes in the 7.14-14.29-microm middle infrared (fingerprint)
      region of liberated thermal luminescence. Several seconds of 2.45-GHz beam
      exposure at 1.5 W cm(-1) is sufficient for detecting polydimethyl siloxane
      lightly wetting the soil through its fundamental Si-CH3 and Si-O-Si stretching
      modes in the fingerprint region. A detection window of thermal opportunity opens
      as the surface attains maximum thermal gradient following irradiation by the
      microwave beam. The contaminant is revealed inside this window by means of a
      simple difference-spectrum measurement. Our goal is to reduce the time needed for
      optimum detection of the contaminant's thermal spectrum to a subsecond exposure
      from a limited intensity beam.

PMID- 18324104
TI  - Limits of optical transmission measurements with application to particle sizing
      techniques.
AB  - Considerable confusion exists regarding the applicability limits of the Bouguer
      Lambert-Beer law of optical transmission. We review the derivation of the law and
      discuss its application to the optical thickness of the light-scattering medium.
      We demonstrate the range of applicability by presenting a method for determining
      particle size by measuring optical transmission at two wavelengths.

PMID- 18324105
TI  - Multiplex coherent anti-Stokes Raman spectroscopy by use of a nearly degenerate
      broadband optical parametric oscillator.
AB  - Optical parametric oscillators (OPO's) provide low-maintenance solid-state
      alternatives to dye lasers. We present results from use of a nearly degenerate
      broadband OPO for multiplex coherent anti-Stokes Raman spectroscopy. The system
      described is capable of generating spectra that cover a range of approximately
      1000 cm(-1).

PMID- 18324106
TI  - Two-color femtosecond experiments by use of two independently tunable Ti:sapphire
      lasers with a sample-and-hold switch.
AB  - We performed femtosecond two-color experiments (four-wave mixing and pump probe)
      using two independently tunable, partially synchronized femtosecond lasers.
      Despite the fact that the jitter is of the order of 5-10 ps, the time resolution
      is limited only by the pulse width when a homemade sample-and-hold switch is
      used.

PMID- 18324108
TI  - Interference effects in far-field diffractive optical elements.
AB  - The effects of interference between closely packed diffraction orders in the far
      field are studied for a number of different scalar-domain diffractive optical
      elements (DOE's). We demonstrate that there are specific order separations that
      minimize the observed degradation in the far-field output uniformity. Finally, a
      DOE that is designed to ensure that the order separation lies near one of these
      minima is compared with a more general design that produces an equivalent far
      field output.

PMID- 18324109
TI  - Characterization of diffraction gratings in a rigorous domain with optical
      scatterometry: hierarchical neural-network model.
AB  - Characterization of microstructures with features from submicrometers to hundreds
      of micrometers requires versatile methods. Profilometry and optical microscopy
      cannot cope with submicrometer features, and atomic-force microscopy, scanning
      electron microscopy, and near-field microscopy are inherently slow, off-line
      methods. In optical scatterometry, the laser light scattered from a sample is
      measured and the sample profile is subsequently characterized. We propose the use
      of a two-stage model based on neural networks: rough categorization followed by
      refinement, thus reducing the need for prior information on the sample. We
      simulate the method for a submicrometer diffraction grating characterized by five
      parameters. It is shown that intensity measurements of few diffraction orders by
      use only of one wavelength are enough to yield rms errors of less than 2 nm for
      the parameters (approximately 2-3% of the optimal values of the parameters).

PMID- 18324110
TI  - Phase-shifting method with a normal polariscope.
AB  - In many laboratories of universities and industrial organizations, commercial
      polariscopes have the feature that the relative position of the two quarter-wave
      plates is fixed. This is due to the requirement of transforming a plane
      polariscope to a circular polariscope with greater precision and ease.
      Unfortunately, these polariscopes cannot implement Patterson and Wang's [Strain
      27, 49-56 (1991)] phase-shifting algorithm because this algorithm requires that
      the second quarter-wave plate and the analyzer of the circular polariscope be
      capable of independent rotation. A new phase-shifting method that can be applied
      under these constraints is proposed. A comparative study with Patterson and
      Wang's [Strain 27, 49-56 (1991)] algorithm shows very good agreement.
      Furthermore, it is shown that four phase steps are sufficient to determine both
      the isoclinic and the isochromatic parameters.

PMID- 18324111
TI  - Sensor performance conversions for infrared target acquisition and intelligence
      surveillance-reconnaissance imaging sensors.
AB  - Target acquisition infrared imaging sensors are characterized by their minimum
      resolvable temperature parameter that is translated to the probability of
      identification (Pid) performance estimate for a given target. Intelligence
      surveillance-reconnaissance (ISR) sensors are characterized by the general image
      quality equation to give a national imagery interpretability rating scale (NIIRS)
      performance estimate. Sensors, such as those on Predator and Global Hawk, will
      soon be used for both ISR and target acquisition purposes. We present a
      performance conversion that includes both sensor resolution and sensitivity. We
      also provide the first empirical results to our knowledge ever to be presented
      that relate NIIRS and Pid for a given set of targets.

PMID- 18324112
TI  - Transient deformation measurement with electronic speckle pattern interferometry
      by use of a holographic optical element for spatial phase stepping.
AB  - We have used a computer-generated holographic optical element (HOE) with
      electronic speckle pattern interferometry to calculate the interference phase
      corresponding to the deformation of a test object from a single TV frame. The HOE
      is a modified crossed phase grating that introduces a known phase change between
      the +/-1 diffracted orders, without being translated. The progressive propagation
      of transient mechanical waves was measured with an rms precision of 2pi/30.

PMID- 18324113
TI  - Corrosion monitoring with speckle correlation.
AB  - The changes in the microtopography of a metal surface during a corrosion process
      are measured by decorrelation of the scattered speckle fields under coherent
      illumination. For that purpose a quantitative relation between the decorrelation
      of the scattered light fields and the rate of corrosion is established in a
      theoretical model, based on the statistics of phase and reflectivity changes of
      point scatterers at the surface. The speckle fields are recorded by a CCD camera
      and processed numerically in a computer, yielding the standard deviation of the
      topography changes with nanometer sensitivity. From the analysis of a series of
      images taken at equal time intervals during the corrosion process, the degree of
      interrelation among subsequent topography changes is calculated.

PMID- 18324114
TI  - Dynamic measurements of internal three-dimensional displacement fields with
      digital speckle photography and flash x rays.
AB  - A metrology system is presented that measures internal three-dimensional (3-D)
      displacement fields. The system uses a stereo pair of flash x-ray heads and
      correlation analysis to measure the true deformation of a layer of x-ray
      absorbent particles inside the specimen. The 3-D deformation field inside blocks
      of polyester was determined. The polyester blocks were impacted by a 9-mm steel
      ball bearing fired from a 9-mm-bore gas gun at a speed of 373.5 +/- 3.0 m s(-1).
      At a given time after impact, a short-duration (30 ns) flash x-ray pulse exposes
      the x-ray radiographs and freezes the events during impact. Thereafter, the x-ray
      radiographs are scanned into a personal computer and analyzed as in digital
      speckle photography.

PMID- 18324115
TI  - Telecentric three-dimensional sensor with a liquid mirror for large-object
      inspection.
AB  - We describe a device that applies the advantages of the space invariance of
      telecentric triangulation with the measurement of large objects (1 m(3)). Because
      the scan motion of the laser beam is decoupled from the physical transport of the
      sensor head, the fast scanning of large volumes becomes feasible. The device
      consists of a triangulation laser telemeter head that uses a large liquid primary
      mirror and an aspheric secondary mirror to realize the telecentric f-theta
      objective. We propose using liquid-mirror technology to make low-cost large
      objectives that have low f numbers, a diffraction-limited performance, and low
      scattering in the visible. This new optical system is useful for 3-D measurement.
      We discuss the optical configuration of the system and the performance of a
      laboratory prototype. The prototype has a standoff distance of 1.5 m, a
      telecentric scan as long as 1 m, a depth of view of 1 m, and a relative depth
      resolution of 0.5-1 mm.

PMID- 18324116
TI  - Thickness-profile measurement of transparent thin-film layers by white-light
      scanning interferometry.
AB  - White-light scanning interferometry is increasingly used for precision profile
      metrology of engineering surfaces, but its current applications are limited
      primarily to opaque surfaces with relatively simple optical reflection behavior.
      A new attempt is made to extend the interferometric method to the thickness
      profile measurement of transparent thin-film layers. An extensive frequency
      domain analysis of multiple reflection is performed to allow both the top and the
      bottom interfaces of a thin-film layer to be measured independently at the same
      time by the nonlinear least-squares technique. This rigorous approach provides
      not only point-by-point thickness probing but also complete volumetric film
      profiles digitized in three dimensions.

PMID- 18324117
TI  - Low-coherence interferometry with synthesis of coherence function.
AB  - Synthesis of a coherence function by manipulation of the spectral phase of low
      coherent light with a segmented liquid-crystal phase modulator and its
      application in a low-coherence interferometry are described. Effects of space
      time coupling caused at diffractive gratings and second-order dispersion at the
      spatial light modulator on the coherence function synthesis are theoretically and
      experimentally verified. Various coherence functions can be shaped with phase
      only masks designed by simulated annealing optimization algorithm. We utilized
      this technique for a novel optical low-coherence reflectometry without any
      mechanical movement for scanning optical delay.

PMID- 18324118
TI  - Absolute interferometry with a 670-nm external cavity diode laser.
AB  - In the past few years there has been much interest in use of tunable diode lasers
      for absolute interferometry. Here we report on use of an external cavity diode
      laser operating in the visible (lambda approximately 670 nm) for absolute
      distance measurements. Under laboratory conditions we achieve better than 1
      microm standard uncertainty in distance measurements over a range of 5 m, but
      significantly larger uncertainties will probably be more typical of shop-floor
      measurements where conditions are far from ideal. We analyze the primary sources
      of uncertainty limiting the performance of wavelength-sweeping methods for
      absolute interferometry, and we discuss how errors can be minimized. Many errors
      are greatly magnified when the wavelength sweeping technique is used; sources of
      error that are normally relevant only at the nanometer level when standard
      interferometric techniques are used may be significant here for measurements at
      the micrometer level.

PMID- 18324119
TI  - Imaging properties in two-photon excitation microscopy and effects of refractive
      index mismatch in thick specimens.
AB  - The detrimental effects of a refractive-index mismatch on the image formation in
      a two-photon microscope were investigated. Point-spread functions (PSF's) were
      recorded with an oil-immersion objective numerical aperture (NA) of 1.3 and a
      water-immersion objective NA of 1.2 in an aqueous sample at different depths. For
      the oil-immersion objective the enlargement of the PSF volume with increasing
      depth yields an axial and a lateral loss in resolution of approximately 380% and
      160%, respectively, at a 90-microm depth in the sample. For the water-immersion
      objective no resolution decrease was found. Measurements on a thick aqueous
      biofilm sample shows the importance of matching the refractive index between
      immersion fluid and sample. With a good match, no loss in image resolution is
      observed.

PMID- 18324120
TI  - High-speed, two-photon scanning microscope.
AB  - We have developed a high-speed two-photon microscope with submicrometer
      resolution in real time. The imaging speed improvement of this system is obtained
      by the use of a high-speed polygonal mirror scanner. The maximum achievable
      scanning rate is 40 micros/line, which is approximately 100 times faster than
      conventional scanning microscopes. High-resolution fluorescence images were
      recorded in real time by an intensified CCD camera. Using this instrument, we
      have resolved cellular architecture in three dimensions and have monitored the
      movements of protozoas. More important, photodamage to biological specimens
      during video-rate imaging can be minimized with two-photon excitation as compared
      with other one-photon modalities.

PMID- 18324121
TI  - Design of a diluted aperture by use of the practical cutoff frequency.
AB  - We analyze the imaging performance of a number of diluted-aperture
      configurations, using the modulation transfer function. We select a single figure
      of merit, the practical cutoff frequency, rather than the traditional cutoff
      frequency, as the more useful frequency for the detection of details. Using this
      new parameter, we compare the performance of a number of published aperture
      configurations. On the basis of this analysis a new configuration is proposed for
      the Polar Stratospheric Telescope primary.

PMID- 18324122
TI  - Wave-front generation of Zernike polynomial modes with a micromachined membrane
      deformable mirror.
AB  - We investigate the characteristics of a 37-channel micromachined membrane
      deformable mirror for wave-front generation. We demonstrate wave-front generation
      of the first 20 Zernike polynomial modes, using an iterative algorithm to adjust
      driving voltages. The results show that lower-order-mode wave fronts can be
      generated with good accuracy and large dynamic range, whereas the generation of
      higher-order modes is limited by the number of the actuator channels and the
      working range of the deformable mirror. The speed of wave-front generation can be
      as fast as several hundred hertz. Our results indicate that, in addition to
      generation of wave fronts with known aberrations, the characteristics of the
      micromachined membrane deformable mirror device can be useful in adaptive optics
      systems for compensating the first five orders of aberration.

PMID- 18324124
TI  - Influence of surface roughness on the calculation of optical constants of a
      metallic film by attenuated total reflection.
AB  - The measured optical-constant errors that arise in the Kretschmann configuration
      from surface roughness have been analyzed. The broadening of the half-width and
      the change in the reflection minimum of the attenuated-total-reflection curve
      that are due to the surface roughness are described. Calculation of the correct
      optical constants and silver-film thickness is demonstrated.

PMID- 18324125
TI  - Dependence of the reflectance of a multilayer reflector on the thickness of the
      outer layer.
AB  - At nonnormal incidence, the radiant reflectance of a highly reflecting multilayer
      coating strongly depends on the thickness of the outer layer.

PMID- 18324126
TI  - Sensitivity enhancement of integrated optical sensors by use of thin high-index
      films.
AB  - The proportion of power carried in the superstrate medium by the guided modes of
      integrated optical waveguides can be increased by the addition of a thin high
      index film. Enhanced refractive-index sensing is demonstrated with channel
      waveguide Mach-Zehnder interferometers with Ta(2)O(5) overlays. Sensitivity
      increases by a factor greater than 50, and a detection limit better than 5 x 10(
      7) is obtained. This approach is broadly applicable to sensing at waveguide
      surfaces where the strength of evanescent fields dictates performance.

PMID- 18324127
TI  - Compensation of optical path lengths in extreme-ultraviolet and soft-x-ray
      monochromators for ultrafast pulses.
AB  - The extraction of the spectrum corresponding to a single extreme-ultraviolet
      ultrashort pulse embedded in an extended spectrum may alter the duration of the
      pulse itself. This is due to the spectral filtering of optics and the differences
      in the optical path of the rays caused by ordinary diffraction when a grating is
      used. The basic mechanism that leads to the latter effect is the difference of
      one wavelength of the path length of two rays diffracted at the first order by
      nearby grating grooves. A study of these effects and some possible solutions
      obtained from using a pair of diffraction gratings is presented. The aim of this
      study is the selection without dispersion of one or more high-order laser
      harmonics produced by a pulse lasting a few femtoseconds and interacting with a
      gas jet.

PMID- 18324128
TI  - n-Hindle-sphere arrangement with an exact ray trace for testing hyperboloid
      convex mirrors.
AB  - We present calculations with an exact ray trace to determine the dimensions that
      define one or two Hindle spheres, since the paraxial theory is incongruent for
      convex hyperboloid mirrors with small f numbers. The equations are generalized to
      calculate the dimensions of n Hindle spheres, since in this way it is possible to
      reduce the dimensions of the spheres more. Actual calculations are done for the
      secondary mirrors of the Benemerita Universidad Autonoma de Puebla and Large
      Milimetric Telescopes; experimental results are shown for the latter.

PMID- 18324129
TI  - Effect of telescope alignment on a stellar interferometer.
AB  - For a ground-based stellar interferometer, we investigate the effect of wave
      front distortions that are due to telescope alignment errors and other factors.
      We apply the results to the IR/Optical Telescope Array (IOTA) interferometer. We
      present the computational method used in our simulation program to calculate
      explicitly the wave-front shape from an arbitrarily misaligned telescope. We
      calculate the wave-front shape and variance for a suite of misalignment
      conditions and interpret these results to find allowable tolerances on the
      positions and tilts of the telescope mirrors. We calculate the expected Strehl
      ratios from a total of ten types of factor, including telescope alignment, that
      are expected to be important in a real interferometer. Ranking the expected wave
      front perturbations, we find that three of them, the wave-front curvature from
      atmospheric turbulence, the servo system time constant, and the flatness of the
      relay optics surfaces, are more significant than the telescope alignment factor.
      We compare observational experience at IOTA with our model estimate of the
      overall Strehl ratio in the visual and the infrared, finding moderately good
      agreement and, more important, a guide for future instrumental improvements.

PMID- 18324130
TI  - Hybrid Monte Carlo for photon transport through optically thick scattering media.
AB  - A Monte Carlo simulation code developed to model time-domain transillumination
      measurements with small-area detectors through an optically thick scattering slab
      is presented. A hybrid approach has been implemented to reduce calculation times.
      Most of the scattering slab is treated stochastically, albeit with variance
      reduction techniques and the isotropic diffusion similarity rule. The
      contribution to the output signal per unit area and time of photon packets
      propagating in a thin slice near the output face of the slab is calculated
      analytically after each propagation step. This approach drastically reduces the
      calculation time but produces spikes in the temporal signals.

PMID- 18324131
TI  - Investigation of the laserlike behavior of polymeric scattering gain media under
      subpicosecond laser excitation.
AB  - The narrowing effects of scatterers on the lifetime and the spectral width of the
      laser-induced fluorescence of organic dyes hosted in poly(methyl methacrylate)
      polymer sheets were studied. The excitation source was a distributed-feedback dye
      laser emitting 0.5-ps pulses at 496 nm. Spectral and temporal features were
      recorded simultaneously on a spectrograph-streak-camera detection system. The
      results were then compared with those obtained from dye solutions in methanol
      that were recorded in previous studies. The effects of the different host
      environments on the fluorescence characteristics of the dye were thus
      investigated. These effects are currently studied when the dye is inserted into
      human tissue in an attempt to boost tumor detection and photodynamic-therapy
      efficiency. Some initial results are presented.

PMID- 18324132
TI  - Multistage optical system for broadcasting and switching information.
AB  - Conventional switching systems connect each input channel to one output channel.
      Broadcasting systems permit the connection of each input channel to more than a
      single output. A broadcast 2 x 2 switch is presented. This switch is an extension
      of the standard bypass-exchange switch. It allows for the broadcasting of the
      inputs in addition to the conventional modes. Multistage interconnection networks
      can be constructed with this switch as the basic building block. Such networks
      will extend their capabilities, allowing for broadcasting features. Three
      implementations of this type are described, and experimental results for the 2 x
      2 switch are also presented.

PMID- 18324133
TI  - On-axis joint transform correlation based on a four-level power spectrum.
AB  - We propose a method to obtain a single centered correlation with use of a joint
      transform correlator. We analyze the required setup to carry out the whole
      process optically, and we also present experimental results.

PMID- 18324134
TI  - Experimental systems implementation of a hybrid optical-digital correlator.
AB  - A high-speed hybrid optical-digital correlator system was designed, constructed,
      modeled, and demonstrated experimentally. This correlator is capable of operation
      at approximately 3000 correlations/s. The input scene is digitized at a
      resolution of 512 x 512 pixels and the phase information of the two-dimensional
      fast Fourier transform calculated and displayed in the correlator filter plane at
      normal video frame rates. High-fidelity reference template images are stored in a
      phase-conjugating optical memory placed at the nominal input plane of the
      correlator and reconstructed with a high-speed acousto-optic scanner; this allows
      for cross correlation of the entire reference data set with the input scene
      within one frame period. A high-speed CCD camera is used to capture the
      correlation-plane image, and rapid correlation-plane processing is achieved with
      a parallel processing architecture.

PMID- 18324135
TI  - Optical implementation of segmented composite filtering.
AB  - We investigate possible performance improvements of coherent optical correlators
      by using an appropriate filter design. Multidecision strategies are often
      required in high-level image-processing tasks. For an optical system
      characterized by a given space-bandwidth product we show that the filter design
      plays a crucial role in satisfying both system and processing requirements, with
      respect to the optimization of the encoding capacity. This leads us to the
      definition of segmented composite filtering, which is discussed in terms of
      processing performance. This filtering is assessed experimentally in the case of
      a face-recognition problem.

PMID- 18324136
TI  - Computer-generated holograms of images reconstructed on curved surfaces.
AB  - When one illuminates a computer-generated hologram by a plane wave, the obtained
      two-dimensional image is usually displayed on a planar plane. Other possibilities
      for reconstructing images on arbitrary curved surfaces are discussed herein. As
      an example, the reconstruction of an image on a virtual spherical surface is
      demonstrated.

PMID- 18324137
TI  - Optimal conditions for thermal fixing of volume holograms in Fe:LiNbO3 crystals.
AB  - We analyze and compare two typical recording and thermal fixing procedures of a
      volume hologram in a Fe:LiNbO(3) crystal (low-high-low procedure and high-low
      procedure). We consider the kinetics of the recording, compensating, and
      developing processes by taking into account the ratio of the conductivities
      between the protons and the electrons as a function of temperature. From the
      analysis the optimal environmental conditions (in terms of the fixing temperature
      and the compensation time) for each fixing procedure can be deduced for a crystal
      with given material parameters.

PMID- 18324138
TI  - Analytical and numerical comparison of encoding methods for computer-generated
      diffractive optical elements.
AB  - We present a new, to our knowledge, analysis of the performances of common
      encoding schemes that are used to design computer-generated diffractive optical
      elements. A statistical analysis of the fringe width and the positional errors,
      which are introduced by the encoding process, is used to calculate their effects
      on the diffraction efficiency and the noise. The analysis is applied to
      interferogram-type encoding methods that are most suited to analytically designed
      elements, in particular, the polygon-fringe-tracing and the bitmap, or mosaic,
      methods. Predictions are verified by use of both numerical simulation and
      existing empirical results. The analysis is used to compare the relative merits
      of the different encoding schemes quantitatively in terms of optical performance
      and computational efficiency criteria.

PMID- 18324139
TI  - Three-dimensional color holographic display.
AB  - Three-dimensional (3D) color holograms are recorded in a cerium-doped, strontium
      barium niobate (SBN:60) photorefractive crystal. These holograms are shown to
      reconstruct true color reproductions of the original object with an observable
      field of view of 37 degrees. Angle multiplexing of two or more 3D color holograms
      is also demonstrated with angle tuning of the reference beam corresponding to a
      separation angle between stored images of 0.082 degrees. Each of these results is
      compared with corresponding theoretical predictions.

PMID- 18324140
TI  - Polymer fiber image guide optical circuits that incorporate free-space add-drop
      components.
AB  - We further extend the capability of a polymer-fiber-image-guide-(PFIG-) based
      optical circuit from a pure point-to-point interconnect scheme to a general
      purpose optical network with data-branching capabilities. Two-dimensional array
      data can be inserted and taken away at free-space add-drop nodes, which are
      implemented with free-space minioptical components. A four-node hybrid circuit
      with PFIG's to transmit bit-parallel data and free-space components to perform
      add-drop is experimentally demonstrated.

PMID- 18324141
TI  - All-optical crossbar switch using wavelength division multiplexing and vertical
      cavity surface-emitting lasers.
AB  - A design for an all-optical crossbar network utilizing wavelength-tunable
      vertical-cavity surface-emitting laser (VCSEL) technology and a combination of
      free-space optics and compact optical waveguides is presented. Polymer waveguides
      route the optical signals from a spatially distributed array of processors to a
      central free-space optical crossbar, producing a passive, all-optical, fully
      connected crossbar network directly from processor to processor. The analyzed
      network could, relatively inexpensively, connect local clusters of tightly
      integrated processors. In addition, it is also believed that such a network could
      be extended, with wavelength reuse, to connect much larger numbers of processors
      in a multicluster network.

PMID- 18324142
TI  - Pixelated liquid-crystal light valve for neural network application.
AB  - The liquid-crystal light valve (LCLV) is a useful component for performing
      integration, thresholding, and gain functions in optical neural networks.
      Integration of the neural activation channels is implemented by pixelation of the
      LCLV, with use of a structured metallic layer between the photoconductor and the
      liquid-crystal layer. Measurements are presented for this type of valve, examples
      of which were prepared for two specific neural network implementations. The valve
      fabrication and measurement were carried out at the State Optical Institute, St.
      Petersburg, Russia, and the modeling and system applications were investigated at
      the Institute of Microtechnology, Neuchatel, Switzerland.

PMID- 18324143
TI  - Multichip free-space global optical interconnection demonstration with integrated
      arrays of vertical-cavity surface-emitting lasers and photodetectors.
AB  - The experimental optical interconnection module of the Free-Space Accelerator for
      Switching Terabit Networks (FAST-Net) project is described and characterized.
      Four two-dimensional (2-D) arrays of monolithically integrated vertical-cavity
      surface-emitting lasers (VCSEL's) and photodetectors (PD's) were designed,
      fabricated, and incorporated into a folded optical system that links a 10 cm x 10
      cm multichip smart pixel plane to itself in a global point-to-point pattern. The
      optical system effects a fully connected network in which each chip is connected
      to all others with a multichannel bidirectional data path. VCSEL's and detectors
      are arranged in clusters on the chips with an interelement spacing of 140 microm.
      Calculations based on measurements of resolution and registration tolerances
      showed that the square 50-microm detector in a typical interchip link captures
      approximately 85% of incident light from its associated VCSEL. The measured
      optical transmission efficiency was 38%, with the losses primarily due to
      reflections at the surfaces of the multielement lenses, which were not
      antireflection coated for the VCSEL wavelength. The overall efficiency for this
      demonstration is therefore 32%. With the measured optical confinement, an optical
      system that is optimized for transmission at the VCSEL wavelength will achieve an
      overall efficiency of greater than 80%. These results suggest that, as high
      density VCSEL-based smart pixel technology matures, the FAST-Net optical
      interconnection concept will provide a low-loss, compact, global interconnection
      approach for high bisection-bandwidth multiprocessor applications in switching,
      signal processing, and image processing.

PMID- 18324144
TI  - Polarization-multiplexed optical memory with urethane-urea copolymers.
AB  - We present a polarization-multiplexed optical memory with urethane-urea
      copolymers. The side chains of the urethane-urea copolymers induce cis-trans
      isomerization by illumination of blue or green light, and they align
      perpendicular to the linear polarization of the illuminated light, thus producing
      optical anisotropy. We found that the material showed selective anisotropy for
      the particular direction that was perpendicular to that of the recording beam
      polarization. By use of the anisotropic property three different data pages were
      multiplexed at the same spot of the medium. Erasure of the recorded bit data is
      also demonstrated.

PMID- 18324145
TI  - Image restoration from vibrating photographic systems.
AB  - Many photographic systems are located on moving platforms. Because of mechanical
      vibrations that exist on those platforms, the photographed image is distorted. To
      avoid those distortions requires that very complicated mechanical attenuators be
      used. We suggest an optoelectronic image-processing algorithm to overcome the
      distortions caused by such vibrations. The algorithm for different types of
      vibration is reformulated in an exact manner, as opposed to the reformulations of
      previously known calculations. Furthermore, new types of vibration are explored.
      The algorithm is fully computerized and thus avoids the need for attenuating
      devices.

PMID- 18324146
TI  - Ozone differential absorption lidar algorithm intercomparison.
AB  - An intercomparison of ozone differential absorption lidar algorithms was
      performed in 1996 within the framework of the Network for the Detection of
      Stratospheric Changes (NDSC) lidar working group. The objective of this research
      was mainly to test the differentiating techniques used by the various lidar teams
      involved in the NDSC for the calculation of the ozone number density from the
      lidar signals. The exercise consisted of processing synthetic lidar signals
      computed from simple Rayleigh scattering and three initial ozone profiles. Two of
      these profiles contained perturbations in the low and the high stratosphere to
      test the vertical resolution of the various algorithms. For the unperturbed
      profiles the results of the simulations show the correct behavior of the lidar
      processing methods in the low and the middle stratosphere with biases of less
      than 1% with respect to the initial profile to as high as 30 km in most cases. In
      the upper stratosphere, significant biases reaching 10% at 45 km for most of the
      algorithms are obtained. This bias is due to the decrease in the signal-to-noise
      ratio with altitude, which makes it necessary to increase the number of points of
      the derivative low-pass filter used for data processing. As a consequence the
      response of the various retrieval algorithms to perturbations in the ozone
      profile is much better in the lower stratosphere than in the higher range. These
      results show the necessity of limiting the vertical smoothing in the ozone lidar
      retrieval algorithm and questions the ability of current lidar systems to detect
      long-term ozone trends above 40 km. Otherwise the simulations show in general a
      correct estimation of the ozone profile random error and, as shown by the tests
      involving the perturbed ozone profiles, some inconsistency in the estimation of
      the vertical resolution among the lidar teams involved in this experiment.

PMID- 18324147
TI  - Comparison of iterative and monte carlo methods for calculation of the Aureole
      about a point source in the earth's atmosphere.
AB  - Point sources in the atmosphere are surrounded by aureoles because of atmospheric
      scattering. The properties of an aureole were calculated by use of a Monte Carlo
      approach and an iterative method for an isotropic source and an axially symmetric
      emission source inside an infinite homogeneous atmosphere. The influence of
      single-scattering albedo, optical depth between source and observer, and source
      intensity anisotropy were studied from both approaches. For each situation, the
      limits and advantages of the Monte Carlo technique and the iterative method are
      described.

PMID- 18324148
TI  - All-weather ultraviolet solar spectra retrieved at a 0.5-Hz sampling rate.
AB  - A measurement scheme and an algorithm have been developed to retrieve global
      irradiance ultraviolet solar spectra (290-400 nm) at a sampling rate of 0.5 Hz.
      The algorithm combines spectral irradiance measurements performed with a slow (a
      few minutes) scanning spectroradiometer (Optronic Model OL752) and a moderate
      bandwidth multichannel radiometer (Biospherical ground-based ultraviolet
      radiometer Model 541). The filter radiometer instrument allows for continuous
      observations of global UV radiation at five channels (approximately 10-nm
      bandwidth), performed simultaneously with spectral measurements. Information
      about changing cloud conditions during a spectral scan was retrieved from filter
      measurements and applied to spectral data, hence estimated spectra without cloud
      variations could be constructed. The quality of the estimated spectra depends on
      data quality from both instruments. The method works well in all kinds of weather
      conditions, as long as the Sun is above the horizon and none of the instruments
      are hampered by measurement errors.

PMID- 18324149
TI  - Far-field propagation of an off-axis Gaussian wave.
AB  - Based on a far-field asymptotic solution of the Helmholtz equation a vector
      theory to describe the propagation of an off-axis Gaussian wave is developed, the
      accurate formulas represented in terms of elementary functions are derived, and
      the propagation properties such as wave spot size and divergence angle are
      discussed in detail. The applicable range of scalar theory is also presented. A
      relative error criterion of optical intensity is given by epsilon = sin(2) alpha.

PMID- 18324150
TI  - High-efficiency dielectric reflection gratings: design, fabrication, and
      analysis.
AB  - We report on reflection gratings produced entirely of dielectric materials. This
      gives the opportunity to enhance the laser damage threshold over that occurring
      in conventional metal gratings used for chirped-pulse-amplification, high-power
      lasers. The design of the system combines a dielectric mirror and a well-defined
      corrugated top layer to obtain optimum results. The rules that have to be
      considered for the design optimization are described. We optimized the parameters
      of a dielectric grating with a binary structure and theoretically obtained 100%
      reflectivity for the -1 order in the Littrow mounting for a 45 degrees angle of
      incidence. Subsequently we fabricated gratings by structuring a low-refractive
      index top layer of a multilayer stack with electron-beam lithography. The
      multilayer system was fabricated by conventional sputtering techniques onto a
      flat fused-silica substrate. The parameters of the device were measured and
      controlled by light scatterometer equipment. We measured 97% diffraction
      efficiency in the -1 order and damage thresholds of 4.4 and 0.18 J/cm(2) with 5
      ns and 1-ps laser pulses, respectively, at a wavelength of 532 nm in working
      conditions.

PMID- 18324151
TI  - Coupling of a laser diode to single-mode fiber with an upside-down tapered lens
      end.
AB  - We present in detail a simple analysis of the coupling efficiency and possible
      transverse and angular misalignment losses of a laser diode to single-mode, step
      index fiber excitation with an upside-down tapered lens (UDTL) end, drawn by
      molding the end of a step-index fiber. The analysis employs our recently
      formulated ABCD matrix for an UDTL and has the advantage of simplicity compared
      with complicated methods involving cumbersome numerical integrations. Both the
      analysis and the results should be useful in designing coupling optics that use
      such lenses in the context of probable misalignments.

PMID- 18324152
TI  - Low-frequency and high-frequency all-fiber modulators based on birefringence
      modulation.
AB  - In-line optical modulators with low insertion losses and high maximum optical
      powers are required for Q switching and cavity dumping of fiber lasers as well as
      for nonlinear optical-fiber experiments. We report the design of polarimetric all
      fiber modulators based on optical-fiber birefringence modulation combined with an
      all-fiber polarizer. Birefringence modulation involves a piezoelectric ceramic
      tube. This simple technique permits efficient low-frequency and high-frequency
      harmonic modulation, up to the megahertz range, as well as modulation of pulses
      shorter than 1 micros.

PMID- 18324153
TI  - Experimental determination of the upconversion rate in erbium-doped silicate
      glasses.
AB  - A new experimental method for direct determination of the upconversion
      coefficient C(up) in Er-doped glasses is presented. This method is based on
      measurement of the dependence on pump power of the fluorescence quantum yield at
      1.54 microm and of the excited-state absorption. Two methods are used for
      determination of the population of the excited Er ions. The first is based on the
      measurement of the variation in stimulated emission and on the variation in
      ground-state absorption for the (4)I(15/2)<-->(4)I(13/2) transition range. In the
      second, the excited-state absorption is measured for the (4)I(13/2) -->(4)F(7/2)
      transition. This method is successfully applied to Er-doped silicate glass
      fibers. The value of C(up) experimentally obtained is in good agreement with
      previously published results.

PMID- 18324156
TI  - Vicarious calibration of the moderate-resolution imaging spectroradiometer
      airborne simulator thermal-infrared channels.
AB  - We made an experimental vicarious calibration of the Moderate Resolution Imaging
      Spectroradiometer (MODIS) Airborne Simulator (MAS) thermal infrared (TIR) channel
      data acquired in the field campaign near Mono Lake, Calif. on 10 March 1998 to
      demonstrate the advantage of using high-elevation sites in dry atmospheric
      conditions for vicarious calibration. With three lake-surface sites and one snow
      field site, we estimated the MAS noise-equivalent temperature difference as 0.7
      1.0 degrees C for bands 30-32 in the 3.68-4.13-microm region and 0.1-0.5 degrees
      C for bands 42, 45, 46, and 48 in the 8-13.5-microm region. This study shows that
      the MAS calibration error is within +/-0.4 degrees C in the split-window channels
      (at 11 and 12 microm) and larger in other TIR channels based on the MAS data over
      Mono Lake and in situ measurement data over the snow-field site.

PMID- 18324157
TI  - Spectrocolorimetric control of ancient documents postablation with excimer
      lasers.
AB  - The application of excimer lasers in ablation, cleaning, and restoration for the
      recovery of paper and parchment manuscripts is a recently implemented technique.
      A report of the use of excimer lasers in a cleaning process by which mud was
      removed from Islamic papers and parchments is presented. It was found that,
      because of the close proximity of the binding energies of paper to paper and of
      paper to mud, it was difficult to maintain control of the ablation process.
      However, the substrate was not affected. Spectrocolorimetry was used as a
      technique to detect the effects of ablation on cleaned areas of the manuscripts
      in terms of change in color appearance and severity of aging postablation. The
      analysis was performed by comparison of treated and untreated areas. Mathematical
      modeling was developed to define a representative original color and a color
      distribution parameter. Improvements in the measuring method were made to yield
      the required precision for evaluating differences in color produced by laser
      ablation and to follow the color evolution after ablation. Results show that the
      effects of restoration, aging, and the environmental conditions can be
      individually identified under certain conditions. The method has applications in
      other domains.

PMID- 18324158
TI  - Frequency-dependent graded reflectivity mirror: characterization and laser
      implementation.
AB  - We present a theoretical and experimental investigation of a new family of
      variable reflectivity mirrors, based on frustrated total internal reflection and
      interference effects. These mirrors are sensitive to frequency in the sense that
      their transverse reflectivity distribution changes significantly as a function of
      the frequency of light. The mirror reported here shows total power reflectivity
      changes of 50% within 8.0 GHz. The mirror was tested as the output coupler of an
      unstable resonator in a Nd:YAG laser working in the free-running regime. This
      configuration was compared with the standard stable multimode resonator
      configuration. The beam divergence was reduced by more than 1 order of magnitude
      and the output power was reduced by only 10%. The laser resonator mode
      competition that is due to the frequency-dependent mirror reflectivity
      distribution is discussed.

PMID- 18324159
TI  - Surface-grating distributed bragg reflector quantum-well lasers fabricated in
      AlGaAs-GaAs asymmetric epitaxial waveguides.
AB  - Ridge waveguide lasers, integrated with single deep-surface distributed Bragg
      reflectors (DBR's) in the passive section, were fabricated with a GaAs-AlGaAs
      double-quantum-well structure in an asymmetric waveguide. Third-order gratings,
      with a period of 389 nm and defined by holographic lithography, were formed by
      low-damage reactive ion etching processes. The grating losses and optical
      coupling coefficients were estimated, in particular, by use of the relationship
      between the real and the effective grating lengths that were computed and
      reexamined by measurements of grating periodicity and mode spacing. By use of two
      different geometries, we produced guide lines for obtaining high-performance
      lasing properties for these surface-grating DBR lasers. Additionally, a detailed
      analysis of lasing wavelength shifts was carried out for this study. It was found
      that injected-carrier-induced effects shift the lasing wavelength much more than
      gain-loss competition within an extended DBR laser cavity.

PMID- 18324160
TI  - Analytical expression for the hysteresis loop width of bistable tunable external
      cavity semiconductor lasers.
AB  - We investigated the power-frequency bistability of a grating external cavity
      laser diode (ECLD), which operates in the strong feedback regime, by studying the
      threshold carrier density and related refractive index. The frequency width of
      the hysteresis loop has been expressed in an explicit analytical form in terms of
      the linewidth enhancement factor, and the reflectivities of the external grating
      reflector as well as the diode facet that faces it.

PMID- 18324161
TI  - Singlet oxygen and dye-triplet-state quenching in solid-state dye lasers
      consisting of pyrromethene 567-doped poly(methyl methacrylate).
AB  - Solid-state dye lasers based on poly(methyl methacrylate) (PMMA) doped with
      Pyrromethene 567 dye (P567) have been investigated. The preparation techniques
      employed provided high photostability and laser damage threshold for P567 in pure
      PMMA with 270,000 pulses emitted before the conversion efficiency fell to half
      its initial value for a pump fluence of 0.16 J cm(-2). When PMMA was modified
      with 1, 4-diazobicyclo [2, 2, 2] octane singlet oxygen quencher, the longevity
      increased to 550,000 pulses, corresponding to a normalized photostability of 270
      GJ mol(-1). Modification of PMMA with a triplet quencher (perylene) yielded no
      improvement, but in ethanol solutions both additives enhanced photostability. It
      is possible that in PMMA, stabilization by means of triplet quenching that
      depends on dye diffusion is prevented but that stabilization by means of singlet
      oxygen quenching that depends on the faster oxygen diffusion rate will succeed.

PMID- 18324162
TI  - Saturable absorber Co2+:MgAl2O4 crystal for Q switching of 1.34-microm Nd3+:YAlO
      3 and 1.54-microm Er3+:glass Lasers.
AB  - Saturable-absorber Q switching of a neodymium-doped YAlO(3) laser at 1.34 microm
      and an erbium-doped glass laser at 1.54 microm with a Co(2+):MgAl(2)O(4) crystal
      was demonstrated. Q-switched 1.34-microm pulses of 19-mJ energy and 60-ns
      duration and Q-switched 1.54-microm pulses of 2.7-mJ energy and 75-ns width were
      obtained. The ground-state absorption cross sections of the Co(2+):MgAl(2)O(4)
      crystal were estimated to be (2.8 +/- 0.4) x 10(-19) and (3.5 +/- 0.6) x 10(-19)
      cm(2) at 1.34 and 1.54 microm, respectively. The (4)T(1)((4)F)-->(4)A(2)
      relaxation time of the Co(2+) ion in the MgAl(2)O(4) crystal was measured to be
      approximately 350 ns.

PMID- 18324163
TI  - Multiple-prism grating solid-state dye laser oscillator: optimized architecture.
AB  - A multiple-prism grating solid-state dye laser oscillator was demonstrated with
      its grating, deployed in a Littrow configuration, under total illumination at
      reduced intracavity beam expansion. This compact cavity yields laser linewidths
      in the 350-MHz range and smooth temporal pulses with a near-Gaussian profile.

PMID- 18324164
TI  - Polarization characteristics of Spectralon illuminated by coherent light.
AB  - The Multiangle Imaging Spectroradiometer makes use of an onboard calibration
      system that includes two Spectralon panels that are used to reflect sunlight into
      the cameras. During preflight testing, these panels were quantified in terms of
      their bidirectional reflectance distribution function, which was measured as a
      function of the source-incident and detector view angles and at laser wavelengths
      of 442.0, 632.8, and 859.9 nm. Principal plane measurements are presented in
      which polarizations of the source and detector are analyzed. These data are
      unique and valuable in modeling Spectralon reflectance properties and for
      experiments in which polarization sensitivities are important.

PMID- 18324165
TI  - Excitation of capillary waves in strongly absorbing liquids by a modulated laser
      beam.
AB  - Several mechanisms for the excitation of capillary waves and for the development
      of the average deformation of a liquid surface under the action of a modulated
      laser beam are considered. The amplitude of the capillary wave in a strongly
      absorbing solution of the dye LDS 751 in ethylene glycol is experimentally
      studied as a function of laser intensity. Consecutive changes in the predominant
      mechanism of the excitation with increasing laser intensity are observed and
      described. At low laser intensities the mechanism connected with the creation of
      a surface tension gradient prevails. This mechanism becomes nonlinear with
      increasing influence of the convective motion. In addition, pressure pulsations
      of the convective flow start to contribute significantly to the generation
      process. The resonances of capillary waves in a cylindrical container are also
      investigated and used for determining the surface tension and viscosity of the
      liquid.

PMID- 18324166
TI  - Retrieval of cloud optical parameters from space-based backscatter lidar data.
AB  - We present an approach to estimating the multiple-scattering (MS) contribution to
      lidar return signals from clouds recorded from space that enables us to describe
      in more detail the return formation at the depth where first orders of scattering
      dominate. Estimates made have enabled us to propose a method for correcting
      solutions of single-scattering lidar equations for the MS contribution. We also
      describe an algorithm for reconstructing the profiles of the cloud scattering
      coefficient and the optical thickness tau under conditions of a priori
      uncertainties. The approach proposed is illustrated with results for optical
      parameters of cirrus and stratiform clouds determined from return signals
      calculated by the Monte Carlo method as well as from return signals acquired with
      the American spaceborne lidar during the Lidar In-Space Technology Experiment
      (LITE).

PMID- 18324167
TI  - Special relativity corrections for space-based lidars.
AB  - The theory of special relativity is used to analyze some of the physical
      phenomena associated with space-based coherent Doppler lidars aimed at Earth and
      the atmosphere. Two important cases of diffuse scattering and retroreflection by
      lidar targets are treated. For the case of diffuse scattering, we show that for a
      coaligned transmitter and receiver on the moving satellite, there is no angle
      between transmitted and returned radiation. However, the ray that enters the
      receiver does not correspond to a retroreflected ray by the target. For the
      retroreflection case there is misalignment between the transmitted ray and the
      received ray. In addition, the Doppler shift in the frequency and the amount of
      tip for the receiver aperture when needed are calculated. The error in estimating
      wind because of the Doppler shift in the frequency due to special relativity
      effects is examined. The results are then applied to a proposed space-based
      pulsed coherent Doppler lidar at NASA's Marshall Space Flight Center for wind and
      aerosol backscatter measurements. The lidar uses an orbiting spacecraft with a
      pulsed laser source and measures the Doppler shift between the transmitted and
      the received frequencies to determine the atmospheric wind velocities. We show
      that the special relativity effects are small for the proposed system.

PMID- 18324168
TI  - Scanning lidar with a coupled radar safety system.
AB  - A small scanning three-wavelength lidar system at NASA Langley Research Center in
      Hampton, Virginia, has been used since 1992 to make atmospheric measurements on
      stratospheric and upper tropospheric aerosols and on the evolution of aircraft
      exhaust plumes. Many of these measurements have been made away from the zenith,
      and, to reduce the hazard to air traffic produced by the laser beam, a radar
      safety device has been installed. The radar application is original in that the
      radar beam is made collinear with the laser beam by use of a dichroic mirror that
      transmits the laser radiation and reflects the microwaves. This mirror is
      inserted into the outgoing optical path prior to the radiation from both the
      radar and the laser passing through the independent scanning unit. Tests of the
      complete system show that the lidar and radar beams remain collocated as they are
      scanned and that the radar can be used to inhibit the laser prior to an aircraft
      passing through the beam.

PMID- 18324169
TI  - Modeling the performance of direct-detection Doppler lidar systems including
      cloud and solar background variability.
AB  - Previous modeling of the performance of spaceborne direct-detection Doppler lidar
      systems assumed extremely idealized atmospheric models. Here we develop a
      technique for modeling the performance of these systems in a more realistic
      atmosphere, based on actual airborne lidar observations. The resulting
      atmospheric model contains cloud and aerosol variability that is absent in other
      simulations of spaceborne Doppler lidar instruments. To produce a realistic
      simulation of daytime performance, we include solar radiance values that are
      based on actual measurements and are allowed to vary as the viewing scene
      changes. Simulations are performed for two types of direct-detection Doppler
      lidar system: the double-edge and the multichannel techniques. Both systems were
      optimized to measure winds from Rayleigh backscatter at 355 nm. Simulations show
      that the measurement uncertainty during daytime is degraded by only approximately
      10-20% compared with nighttime performance, provided that a proper solar filter
      is included in the instrument design.

PMID- 18324170
TI  - Effects of a nonlinear response of the fourier-transform infrared open-path
      instrument on the measurements of some atmospheric gases.
AB  - The response of a Fourier-transform infrared (FTIR) instrument to changes in
      absorbance is inherently nonlinear for a number of reasons. One is that the
      interferogram acquired by the FTIR is truncated and then apodized before further
      processing of the data is accomplished. A commonly used apodization function in
      open-path FTIR research is triangular apodization, and all the research presented
      here has been done with that function. We calculated a set of absorption spectra
      by using the HITRAN database, covering ranges in both concentration and
      temperature for water, ammonia, and methane. Plots of these data reveal nonlinear
      results. The commonly used analysis technique, classical least squares, assumes
      that the response is linear. We describe some of the effects of this nonlinearity
      and present ways to address these effects.

PMID- 18324171
TI  - Infrared and visible fourier-transform spectra of sulfuric-acid-water aerosols at
      230 and 294 K.
AB  - The extinction spectra of aqueous sulfuric acid aerosols fully covering the mid
      IR to visible regions from 750 to 23,000 cm(-1) (13.9-0.4 microm) have been
      measured in the laboratory with a Fourier-transform spectrometer. Both large and
      small aerosol particles with compositions of approximately 60-70-wt. % H(2)SO(4)
      were generated and their spectra recorded at 230 and 294 K. The spectra were
      fitted to a model incorporating room-temperature refractive-index data [Appl.
      Opt. 14, 208 (1975)] and Mie theory calculations to characterize the composition
      and size distributions of the aerosol samples.

PMID- 18324172
TI  - Optical properties of a dispersion of randomly oriented identical aggregates of
      spheres deposited on a plane surface.
AB  - Our previous theory for calculating the scattering pattern from a single
      aggregate of spheres deposited on a dielectric substrate is extended to deal with
      a dispersion of identical aggregates onto the substrate with a random
      distribution of their orientations. To this end the definition of the transition
      matrix of an aggregate is generalized to take account of the presence of the
      substrate; then the transformation properties under rotation of the newly defined
      transition matrix are used to perform analytically the required orientational
      averages. When the patterns calculated with this theory are compared with the
      calculations for a single aggregate, it can easily be seen that the features that
      reveal the anisotropy of the scatterers are not canceled by the averaging
      procedure.

PMID- 18324173
TI  - Virtues of mueller matrix imaging for underwater target detection.
AB  - We present a theoretical analysis on use of polarized light in the detection of a
      model target in a scattering and absorbing medium similar to seawater. Monte
      Carlo numerical simulations are used in the calculation of the effective Mueller
      matrix which describes the scattering process. A target in the shape of a disk is
      divided into three regions, each of which has the same albedo but different
      reduced Mueller matrices. Contrast between various parts of the target and
      background is analyzed in the images created by ordinary radiance, by various
      elements of the Mueller matrix, and by certain suitable combinations of these
      elements. It is shown that the application of polarized light has distinct
      advantages in target detection and characterization when compared with use of
      unpolarized light.

PMID- 18324174
TI  - Frequency dependence in a liquid's complex refractive index measured with
      infrared spectroradiometry.
AB  - A laboratory measurement of wavelength dependence in the real n(lambda) and the
      imaginary k(lambda) parts of a liquid's complex refractive index is presented. A
      known heat flow through the liquid-gas interface is generated while a high
      resolution infrared radiance spectrum is taken simultaneously. Wavelength
      variations of the absorption coefficient allow the emerging radiation to sense
      subsurface temperature gradients. This technique is valid only at intervals at
      which the absorption coefficient is sufficiently low to allow subsurface
      temperatures to be measured. Knowledge of a liquid's thermal conductivity,
      specific heat, and light transmission speed is required. Measurement error
      depends on radiance measurement error and the minimization of atmospheric
      parameters.

PMID- 18324175
TI  - Laser photofragmentation-fragment detection and pyrolysis-laser-induced
      fluorescence studies on energetic materials.
AB  - Trace concentrations of energetic materials such as 2, 4, 6-trinitrotoluene
      (TNT), pentaerythritol tetranitrate (PETN), and hexahydro-1, 3, 5-trinitro-s
      triazine (RDX) are detected by laser photofragmentation-fragment detection (PF
      FD) spectrometry. In this technique, a single laser operating near 227 nm
      photofragments the parent molecule and facilitates the detection of the
      characteristic NO fragment by means of its A (2)Sigma(+)-X (2)Sigma (0, 0)
      transitions near 227 nm. Fragment detection is accomplished by resonance-enhanced
      multiphoton ionization with miniature electrodes and by laser-induced
      fluorescence (LIF) with a photodetector. Experiments are also conducted in the
      visible region by use of 453.85-nm radiation for photofragmentation and fragment
      detection. Sand samples contaminated with PETN and RDX are analyzed by a
      pyrolysis-LIF technique, which involves pyrolysis of the energetic material with
      subsequent detection of the pyrolysis products NO and NO(2) by LIF and PF-LIF,
      respectively, near 227 nm. The application of these techniques to the trace
      analysis of TNT, PETN, and RDX at ambient pressure in room air is demonstrated
      with limits of detection (signal-to-noise ratio, 3) in the low parts-in-10(9) to
      parts-in-10(6) range for a 20-s integration time and 10-120 microJ of laser
      energy at 226.8 nm and approximately 5 mJ at 453.85 nm. An increase in detection
      sensitivity is projected with an increase in laser energy and an improved system
      design. The analytical merits of these techniques are discussed and compared with
      those of other laser-based techniques.

PMID- 18324177
TI  - Diffracted radiance: a fundamental quantity in nonparaxial scalar diffraction
      theory.
AB  - Most authors include a paraxial (small-angle) limitation in their discussion of
      diffracted wave fields. This paraxial limitation severely limits the conditions
      under which diffraction behavior is adequately described. A linear systems
      approach to modeling nonparaxial scalar diffraction theory is developed by
      normalization of the spatial variables by the wavelength of light and by
      recognition that the reciprocal variables in Fourier transform space are the
      direction cosines of the propagation vectors of the resulting angular spectrum of
      plane waves. It is then shown that wide-angle scalar diffraction phenomena are
      shift invariant with respect to changes in the incident angle only in direction
      cosine space. Furthermore, it is the diffracted radiance (not the intensity or
      the irradiance) that is shift invariant in direction cosine space. This
      realization greatly extends the range of parameters over which simple Fourier
      techniques can be used to make accurate calculations concerning wide-angle
      diffraction phenomena. Diffraction-grating behavior and surface-scattering
      effects are two diffraction phenomena that are not limited to the paraxial region
      and benefit greatly from this new development.

PMID- 18324178
TI  - Diffractive optical elements in hybrid lenses: modeling and design by zone
      decomposition.
AB  - We propose to model hybrid optical systems (i.e., lenses with conventional and
      diffractive optical elements) as multiaperture systems in which the images formed
      by each zone of the diffractive optical element should be summed up coherently.
      This new zone decomposition concept is explained and compared with the standard
      diffraction-order expansion with the help of a hybrid triplet example.

PMID- 18324179
TI  - Efficiency calibration of the first multilayer-coated holographic ion-etched
      flight grating for a sounding rocket high-resolution spectrometer.
AB  - We have fabricated the four flight gratings for a sounding rocket high-resolution
      spectrometer using a holographic ion-etching technique. The gratings are
      spherical (4000-mm radius of curvature), large (160 mm x 90 mm), and have a
      laminar groove profile of high density (3600 grooves/mm). They have been coated
      with a high-reflectance multilayer of Mo/Si. Using an atomic force microscope, we
      examined the surface characteristics of the first grating before and after
      multilayer coating. The average roughness is approximately 3 A rms after coating.
      Using synchrotron radiation, we completed an efficiency calibration map over the
      wavelength range 225-245 A. At an angle of incidence of 5 degrees and a
      wavelength of 234 A, the average efficiency in the first inside order is 10.4 +/-
      0.5%, and the derived groove efficiency is 34.8 +/- 1.6%. These values exceed all
      previously published results for a high-density grating.

PMID- 18324180
TI  - Formation of phase gratings on the end of gradient-index lenses with ultraviolet
      ablation at 193 nm.
AB  - We present a simple, cost-effective method for creating diffractive optical
      elements on the surfaces of optical fibers and fiber-optic components by use of
      193-nm ablation techniques. It is an outgrowth of a more fundamental
      investigation of the effects of intense UV radiation fields on SiO2- and Ge-SiO2
      based structures (specifically optical fibers and preforms) and allows the
      inexpensive fabrication of structures such as the suggested evanescent-field
      based sensing device.

PMID- 18324181
TI  - Mode-coupled artifact standard for polarization-mode dispersion: design,
      assembly, and implementation.
AB  - A stack of quasi-randomly oriented quartz plates has been assembled as a
      calibration artifact for mode-coupled polarization-mode dispersion. The design of
      the artifact, the reasons for choosing it, the procedure for its assembly, and
      its implementation are described. Considerable discussion is also devoted to the
      fact that this mode-coupled artifact is limited in scope to polarimetric
      measurement techniques (those that directly measure differential group delay as a
      function of wavelength).

PMID- 18324182
TI  - Rotating-wave-plate Stokes polarimeter for differential group delay measurements
      of polarization-mode dispersion.
AB  - We present a description and detailed uncertainty analysis of a polarization-mode
      dispersion (PMD) measurement system that uses the Jones matrix eigenanalysis
      measurement technique based on a rotating-wave-plate Stokes polarimeter. The
      uncertainty of the system is 3.2 fs (approximately 95% confidence interval) and
      is due primarily to PMD in the fiber leads of the measurement system.

PMID- 18324183
TI  - Trade-off between the spatial and the frequency resolutions in measuring the
      power spectrum of the Brillouin backscattered light in an optical fiber.
AB  - We theoretically analyze the relation between the pulse width of light launched
      into an optical fiber and the resultant power spectrum of spontaneous Brillouin
      backscattered light. Through this analysis, we determine numerically that the
      bandwidth of the Brillouin backscattered light becomes wider, and thus the
      measurement accuracy in determining the peak-power frequency degrades in
      approximately inverse proportion to the launched pulse width. Experimental
      results with various pulse widths are in good agreement with the derived
      theoretical results.

PMID- 18324184
TI  - Fourier analysis applied to the characterization of optical wedges with small
      angles.
AB  - A technique for the measurement of optical wedge parameters is shown. It is based
      on the analysis of the Fourier transform of an interferogram-intensity register.
      In this domain the angle and the edge orientations of the optical wedge can be
      determined through a much simpler procedure than the usual interferogram fringe
      analysis.

PMID- 18324185
TI  - Three-dimensional profilometry based on coded linear-structure light with
      isosceles triangle teeth.
AB  - A method of linearly coded profilometry is proposed. It uses linear-structure
      light with isosceles triangle teeth to code the object being measured and a phase
      shifting technique to decode the profile. For reducing the effect of noise more
      than three equally spaced samples are used, and, according to the least-squares
      method, the general formulas of the decoded phase are given. The experimental
      results of a model of a head are shown.

PMID- 18324186
TI  - Surface characterization of micro-optical components by Foucault's knife-edge
      method: the case of a micromirror array.
AB  - As micro-optical components are introduced into optical systems, accurate surface
      characterization becomes important. We describe a method for quantitative
      evaluation of surface deformations based on Foucault's knife-edge test. By
      measurement of local slopes, the surface shape of each mirror in a micromirror
      array has been reconstructed with a subnanometer accuracy. In addition to low
      order deformation (tilt, curvature, astigmatism), each mirror is seen to be palm
      tree shaped. This may be explained by strain relaxation in the fabrication
      process. Measurement on a conventional concave mirror confirms our method.

PMID- 18324187
TI  - Data-dependent systems profilometry of two-dimensional surfaces.
AB  - Fourier-transform profilometry (FTP) and data-dependent systems profilometry
      (DDSP) are two methods that are available for recovering one-dimensional fine
      surface profiles from the phase of a single interferogram. FTP has already been
      extended to two-dimensional surfaces; a similar extension of DDSP is introduced
      here. Inasmuch as this extension involves autoregressive modeling of the rows or
      columns of an interferogram, the feasibility of using a common model order is
      explored. The common order reduces not only the amount of computation but also
      the errors caused by the heterodyned phase-removal procedure. As autoregression
      requires masking the first few data values, the length of the mask is determined
      by means of a Green's function. A comparison shows that DDSP outperforms FTP in
      roughness measurements in terms of rms and center-line average. The comparison
      also shows that DDSP is able to recover a detailed surface, whereas FTP outlines
      only the global features. An interferogram regeneration procedure provides a
      reference surface for the verification of results.

PMID- 18324188
TI  - Small-angle measurement based on surface-plasmon resonance and the use of magneto
      optical modulation.
AB  - A new, to our knowledge, optical method for small-angle measurement based on
      surface-plasmon resonance (SPR) is presented. In this method the high sensitivity
      of the phase of SPR to the angle of incidence is employed to improve the
      resolution of the measurement of the angle. Small-angle measurement is performed
      by the monitoring of the phase shift resulting from the minute change of the
      angle of incidence with the use of magneto-optical modulation. The validity of
      this method is demonstrated, and a measurement resolution of 0.2 arc sec is
      achieved experimentally.

PMID- 18324189
TI  - Phase-shifted dynamic speckle pattern interferometry at 1 kHz.
AB  - We describe a phase-shifting out-of-plane speckle interferometer operating at 1
      kHz for studying dynamic events. The system is based on a Pockels cell that is
      synchronized to a high-speed video camera to ensure that the phase shifting
      occurs between frames. Phase extraction is performed by use of a standard four
      frame algorithm, and temporal phase unwrapping allows sequences of several
      hundred absolute (rather than relative) displacement maps to be obtained fully
      automatically. The maximum theoretical surface velocity of 67 microm s(-1) is a
      factor of 40 greater than can be achieved with a speckle interferometer based on
      a conventional video camera. We test the system using a target that is displaced
      with constant speed in a direction normal to its surface by means of a
      piezoelectric transducer. The system's performance in a practical situation is
      illustrated with measurements on a thin plate undergoing out-of-plane
      deformation.

PMID- 18324191
TI  - Three-dimensional vision based on a combination of gray-code and phase-shift
      light projection: analysis and compensation of the systematic errors.
AB  - A combination of phase-shift with gray-code light projection into a three
      dimensional vision system based on the projection of structured light is
      presented. The gray-code method is exploited to detect without ambiguity even
      marked surface discontinuities, whereas the phase-shift technique allows the
      measurement of fine surface details. The system shows excellent linearity. An
      overall mean value of the measurement error equal to 40 microm, with a
      variability of approximately +/-35 microm, corresponding to 0.06% of full scale,
      has been estimated. The implementation of the technique is discussed, the
      analysis of the systematic errors is presented in detail, and the calibration
      procedure designed to determine the optimal setting of the measurement parameters
      is illustrated.

PMID- 18324192
TI  - Birefringence measurements in gradient-index rod lenses.
AB  - Stress birefringence can be found in gradient-index (GRIN) materials because they
      contain a variation in composition. GRIN glass fabricated by ion exchange may
      contain stress from two different processes. These include a size difference
      between the exchange and the diffusing ions and a variation in the thermal
      expansion coefficient across the gradient region. The optical properties of the
      stressed material are polarization dependent, and therefore image quality is
      directly affected. We examine birefringence in GRIN rod lenses that have lengths
      more than ten times greater than their diameters. The effects are more easily
      observed in long rod lenses because of the large optical path lengths.

PMID- 18324193
TI  - Optically anisotropic polyethylene-gold nanocomposites.
AB  - Gold colloids coated with a self-assembled monolayer of an alkanethiol were
      introduced into a polyethylene matrix by means of solution-casting techniques. We
      oriented the resulting nanocomposites by uniaxial drawing in the solid state. The
      absorption spectra of the drawn nanocomposites in the visible wavelength region
      were found to depend strongly on the polarization direction of incident light.
      The materials appeared, for instance, red or blue if the light was polarized
      perpendicular or parallel, respectively, to the drawing axis. The observed
      optical anisotropy is thought to originate in the morphology of the composites
      that composed uniaxially oriented, pearl-necklace arrays of nanoparticles with a
      high aspect ratio, as observed in transmission electron microscopy. It is shown
      that the polymer-inorganic nanocomposites can be employed as color polarizing
      filters.

PMID- 18324194
TI  - Local spectral information in the near field with wavelet analysis and entropy.
AB  - In near-field optical microscopy the resolution is strongly related to the
      experimental illumination conditions and to the separation between tip and
      sample. Therefore the spectral information in near-field data (related to the
      resolution in images) can be described only locally as a function of the tip
      sample position. To make a local study of the spectral information in near-field
      data, we use wavelet decomposition that is associated with the calculation of
      entropy. We deduce the resolution from the characteristics of the wavelet, which
      leads to an automatic and numerical evaluation of the resolution in near-field
      data.

PMID- 18324195
TI  - Three-dimensional imaging with optical tweezers.
AB  - We demonstrate a three-dimensional scanning probe microscope in which the
      extremely soft spring of an optical tweezers trap is used. Feedback control of
      the instrument based on backscattered light levels allows three-dimensional
      imaging of microscopic samples in an aqueous environment. Preliminary results
      with a 2-microm-diameter spherical probe indicate that features of approximately
      200 nm can be resolved, with a sensitivity of 5 nm in the height measurement. The
      theoretical resolution is limited by the probe dimensions.

PMID- 18324196
TI  - Analysis and design of modified Wollaston prisms.
AB  - An exact analysis of the working parameters of a modified Wollaston prism is
      presented. Parameters include the output splitting angle, the retardation, and
      the location of the plane of the interference fringes (plane of apparent
      splitting). Results are presented for the entire range of optical axis
      inclinations and wedge angles. Approximate expressions from the literature are
      evaluated. An angle of incidence that causes the plane of the interference
      fringes to be perpendicular to the axis of the optical system is found for each
      configuration analyzed. This is then applied to the design of modified Wollaston
      prisms for Nomarski differential interference contrast microscopy.

PMID- 18324197
TI  - Narrow-bandpass multilayer mirrors for an extreme-ultraviolet Doppler telescope.
AB  - We have developed narrow-bandpass MoSi/Si multilayer mirrors for a Japanese
      sounding-rocket program. A high spectral resolution lambda/Deltalambda exceeding
      40 was achieved by a two-mirror telescope with a multilayer coating. The single
      telescope had two bandpasses in the extreme-UV range for detecting a coronal high
      velocity flow; the wavelength at peak reflectance (hereafter peak wavelength) in
      one of the bandpasses was 210.2 A, situated on the blue side of the target's Fe
      XIV 211.3-A coronal emission line, and the peak wavelength in the other was 213.3
      A on the red side. A high uniformity in a peak wavelength of less than 1 A was
      achieved over a primary (secondary) mirror surface 158 (96) mm in diameter. The
      ratio of the reflectance for the Fe XIV line at 211 A to that for an intense He
      II line as a contaminant at 304 A in the telescope system became 2 x 10(5) owing
      to a wave trap consisting of a single Si layer on the MoSi/Si multilayer. The
      narrow-bandpass (approximately 5-A) telescope was launched on 31 January 1998 by
      sounding rocket S520CN-22, and images of the whole-Sun corona at Fe XIV 211 A
      were successfully obtained.

PMID- 18324198
TI  - Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo.
AB  - Diffuse reflectance spectra were collected from adenomatous colon polyps (cancer
      precursors) and normal colonic mucosa of patients undergoing colonoscopy. We
      analyzed the data by using an analytical light diffusion model, which was tested
      and validated on a physical tissue model composed of polystyrene beads and
      hemoglobin. Four parameters were obtained: hemoglobin concentration, hemoglobin
      oxygen saturation, effective scatterer density, and effective scatterer size.
      Normal and adenomatous tissue sites exhibited differences in hemoglobin
      concentration and, on average, in effective scatterer size, which were in general
      agreement with other studies that employ standard methods. These results suggest
      that diffuse reflectance can be used to obtain tissue information about tissue
      structure and composition in vivo.

PMID- 18324199
TI  - Deposition at low substrate temperatures of high-quality TiO2 films by radical
      beam-assisted evaporation.
AB  - We deposited high-quality TiO2 films by an oxygen-radical beam-assisted
      evaporation (RBE) method at a lower substrate temperature (Ts) than that for a
      TiO2 film deposited by conventional thermal evaporation (TE) with neutral-oxygen
      gas. The films were then evaluated in terms of refractive index, shift of
      wavelength of a peak in the reflection curve, and absorption coefficient. The
      TiO2 films deposited by RBE at Ts < 473 K showed higher refractive indices, were
      more compact, and had lower absorption coefficients than the film deposited by TE
      at Ts = 473 K.

PMID- 18324200
TI  - Strehl ratio and modulation transfer function for segmented mirror telescopes as
      functions of segment phase error.
AB  - We derive the Strehl ratio for a segmented mirror telescope as a function of the
      rms segment phase error and the observing wavelength, with and without the
      effects of the atmosphere. A simple analytical expression is given for the
      atmosphere-free case. Although our specific results are in the context of the
      Keck telescope, they are presented in a way that should be readily adaptable to
      other segmented geometries. We also derive the corresponding modulation transfer
      functions. These results are useful in determining how accurately a segmented
      mirror telescope needs to be phased for a variety of observing applications.

PMID- 18324201
TI  - Observation of the dynamics of live cardiomyocytes through a free-running
      scanning near-field optical microscopy setup.
AB  - We report the observation of live-cell dynamics by noncontact scanning near-field
      optical microscopy (SNOM) modified to work with living biological samples that
      are fully immersed in liquid. We did not use the SNOM setup in strictly near
      field conditions (we used 1-mum constant-height mode); however, we could examine
      the dynamics of rhythmically beating cardiac myocytes in culture with extremely
      high vertical sensitivity below the nanometric range. We could halt scans at any
      point to record localized contraction profiles of the cell membrane. We show that
      the contractions of the organisms changed shape dramatically within adjacent
      areas. We believe that the spatial dependency of the contractions arises because
      of the measurement system's ability to resolve the behavior of individual
      submembrane actin bundles. Our results, combining imaging and real-time recording
      in localized areas, reveal a new, to our knowledge, noninvasive method for using
      SNOM setups for studying the dynamics of live biological samples.

PMID- 18324202
TI  - Noninvasive light-reflection technique for measuring soft-tissue stretch.
AB  - A novel, to our knowledge, sensor for measuring the stretch in soft tissues such
      as skin is described. The technique, which is a modification of two-dimensional
      polarization imaging, uses changes in the reflectivity of polarized light as a
      monitor of skin stretch. Measurements show that the reflectivity increases with
      stretch. Measurements were made on guinea pig skin and on nonbiological
      materials. The changes in reflectivity result from the changes that take place in
      the interface roughness between skin or material layers and the consequential
      changes in the diffuse reflective characteristics of the skin. Conceptually, as
      the roughness of an interface decreases, a smoother reflecting interface is
      produced, resulting in a commensurate increase in specular reflection. A simple
      roughness model correctly predicts the main experimental results. Results can be
      extended easily to real-time stretch analysis of large tissue areas that would be
      applicable for predicting stresses in skin during and after the surgical closure
      of wounds.

PMID- 18324203
TI  - Optical and thermal characterization of albumin protein solders.
AB  - The effect of temperature on the optical and thermal properties of pure and
      indocyanine green-doped albumin protein solders as a function of wavelength has
      been studied between 25 degrees C and 100 degrees C. An increase in the group
      refractive index by up to 4% and a decrease in absorption coefficient
      (approximately 800 nm) by up to 8%, after denaturing the solder specimens in a
      constant-temperature water bath at temperatures of 60-100 degrees C, were not
      significant. The reduced scattering coefficient, however, increased rapidly with
      temperature as the solder changed from being a highly nonscattering medium at
      room temperature to a highly scattering medium at temperatures close to 70
      degrees C. The thermal conductivity, thermal diffusivity, and heat capacity
      increased by up to 30%, 15%, and 10%, respectively. Finally, the frequency factor
      and activation energy were measured to be 3.17 x 10(56) s(-1) and 3.79 x 10(5) J
      mol(-1), respectively, for liquid protein solders (25% bovine serum albumin) and
      3.50 x 10(57) s(-1) and 3.85 x 10(5) J mol(-1), respectively, for solid protein
      solders (60% bovine serum albumin). Incorporation of dynamic optical and thermal
      properties into modeling studies of laser tissue interactions could have a
      significant influence on the determination of the expected zone of damage.

PMID- 18324204
TI  - Influence of saline media on the fluorescence emission of Bacillus spores.
AB  - Single-particle levitation in conjunction with 264.3-nm laser excitation is used
      to measure the fluorescence emission of individual particles of Bacillus globigii
      spores. With precise humidity control, the fluorescence emission of wetted and
      desiccated Bacillus spore particles is measured from 300 to 450 nm. Comparison of
      spectra for Bacillus spores suspended in a standard buffer aqueous solution and
      for a desiccated 10-mum-diameter aggregate Bacillus spore particle shows that the
      spectra is virtually indistinguishable. However, at 85% relative humidity,
      corresponding to a 4.5M sodium chloride solution, the spore spectra redshifts by
      approximately 25 nm. It is postulated that the spectra redshifting is a result of
      specific interactions between the tyrosine fluorophore of the Bacillus spore and
      the phosphate moieties in the buffer solution.

PMID- 18324205
TI  - Diffraction halo function of partially coherent speckle photography.
AB  - We studied the diffraction halo function of partially coherent speckle
      photography, using the theory of partial coherence of light and speckle
      statistics. Numerical calculations were made on the basis of the derived
      expression. It was shown that the anisotropic coherence of the illumination
      induced by the source could lead to the inhomogeneity of the halo distribution.
      An experiment was performed to prove the theoretical predictions.

PMID- 18324206
TI  - Simultaneous multiplane imaging with a distorted diffraction grating.
AB  - We describe a simple technique for simultaneously imaging multiple layers within
      an object field onto a single camera. The approach uses a binary diffraction
      grating in which the lines are distorted such that a different level of defocus
      is associated with each diffraction order. The design of the gratings is
      discussed, and their ability to image multiple object planes is validated
      experimentally. Extension of the technique for spherical-aberration correction is
      described, and it is shown how the gratings can be used as part of a wave-front
      sensing system.

PMID- 18324207
TI  - Temporal Talbot effect in fiber gratings and its applications.
AB  - We show that a temporal effect equivalent to the spatial Talbot effect (self
      imaging) applies to the reflection of periodic pulse trains from linearly chirped
      fiber gratings (LCFG's). For specific input repetition periods the reflected
      signal is an exact replica of the input signal. Input repetition period values
      that give rise to this effect depend on the dispersion coefficient of the
      grating. We propose to use this effect as an alternative for dispersion
      measurement in LCFG's. Furthermore, by using the properties of the temporal
      Talbot effect, we can design linear passive devices (LCFG's) for use as frequency
      multipliers, able to multiply the repetition rate of a given pulse train.

PMID- 18324208
TI  - Nonuniform fast Hankel transform (NUFHT) algorithm.
AB  - We investigate the fast computation of Hankel transforms on a set of nonuniformly
      spaced sample points. Previous fast Hankel transform (FHT) algorithms require the
      sample points to distribute uniformly in a logarithmic scale. This limitation is
      removed here by the use of the newly developed, to our knowledge, nonuniform fast
      Fourier transform algorithm. The resulting nonuniform FHT algorithm has a much
      higher accuracy than the previous FHT algorithms and provides important
      flexibility in many applications.

PMID- 18324209
TI  - Bessel function output from an optical correlator with a phase-only encoded
      inverse filter.
AB  - We report on a technique for producing a Bessel function correlation output for
      an arbitrary input pattern. The central dark spot at the center of the Bessel
      function correlator output is narrower than the width of the normal correlation
      spot and can be extremely useful for locating the center of the correlation
      signal. The Bessel function is produced by convolution of the extremely sharp
      correlation produced by an inverse filter with the Bessel function and is encoded
      with a single phase-only liquid-crystal spatial light modulator. To encode
      amplitude information on the filter, we spatially modulate the phase encoded on
      the filter. Amplitude modulation is obtained by modulation of the diffraction
      efficiency of the phase grating. Experimental results are presented.

PMID- 18324210
TI  - Adaptive computer-based spatial-filtering method for more accurate estimation of
      the surface velocity of debris flow.
AB  - An adaptive computer-based spatial-filtering velocimeter to measure the surface
      velocity of a natural debris flow with high accuracy is described that can adjust
      the filter parameters, specifically, the slit width of the filter, based on the
      surface-pattern characteristics of the flow. A computer simulation confirms the
      effectiveness of this technique. The surface velocity of a natural debris flow at
      the Mt. Yakedake Volcano, Japan, was estimated by this adaptive method, and the
      results were compared with those obtained by two other methods: hardware-based
      spatial filtering and normal computer-based spatial filtering.

PMID- 18324211
TI  - Application of a photopolymer to a holographic reflector for reflective liquid
      crystal displays.
AB  - A photopolymer for fabrication of volume-type transmission holograms, which are
      used primarily on the holographic reflector for reflective LCD's, is reported.
      This photopolymer consists of bisphenol-type epoxy resin and an acrylic monomer
      with diaryliodonium salt and 3-ketocoumarin as a complex initiator. The chemistry
      of the imaging formation is based on the radical polymerization of the monomer
      initiated by a holographic exposure, followed by the cationic polymerization of
      epoxy resin by UV exposure after postexposure baking. The yellowish color of the
      hologram derivatives that resulted from the sensitizing dye and from the
      photospeed were improved to satisfy the specifications for the holographic
      reflector. The holographic reflector now gives brighter images.

PMID- 18324212
TI  - Iterative algorithm for determining optimal beam profiles in a three-dimensional
      space.
AB  - A new, to our knowledge, iterative algorithm for achieving optimization of beam
      profiles in a three-dimensional volume is presented. The algorithm is based on
      examining the region of interest at discrete plane locations perpendicular to the
      propagation direction. At each such plane an intensity constraint is imposed
      within a well-defined transverse spatial region of interest, whereas the phase
      inside that region as well as the complex amplitude outside the region is left
      unchanged from the previous iteration. Once the optimal solution is found, the
      mask that generates the desired distribution can be readily implemented with a
      planar diffractive optical element such as a computer-generated hologram. Several
      computer simulations verified the utility of the proposed approach.

PMID- 18324213
TI  - Analysis of optimal centroid estimation applied to Shack-Hartmann sensing.
AB  - The problem of estimating the centroid of an incoherently imaged point with a CCD
      array is analyzed. An exact analysis is presented that uses the actual short
      exposure function at the CCD instead of the traditional Gaussian approximation.
      The analysis shows that, for Poisson noise, the centroid variance depends on the
      CCD size and that truncation effects play a significant part in determining the
      optimum CCD size. The effects of this on a wave-front reconstruction formed by a
      Shack-Hartmann sensor are described.

PMID- 18324214
TI  - Single-step UV recording of sinusoidal surface gratings in hybrid solgel glasses.
AB  - Efficient surface gratings are UV imprinted in an acrylate-rich hybrid solgel
      glass. Structural changes occurring in the material upon exposure to light are
      investigated. Large amplitude modulation (700 nm) and low surface roughness (0.2
      nm) were measured by atomic force microscopy. Diffraction efficiencies were found
      to be close to theoretical predictions. The method of fabrication does not
      involve any etching step, and an all-UV process is proposed. The gratings are
      resistant to temperature and to solvent effects. These devices could have useful
      applications in sensor and spectroscopic devices.

PMID- 18324215
TI  - Spatial soliton angular deflection logic gates.
AB  - A generalized interaction geometry between orthogonally polarized optical spatial
      solitons is presented in which a weak signal soliton induces a small angular
      deflection of a stronger power supply, or pump, soliton, resulting in a spatially
      resolved shift of the pump at the gate output. This geometry allows for the all
      optical realization of true three-terminal, inverting and restoring logic devices
      with gain, which can serve as building blocks for more complex logic operations.
      In addition, the effects of linear and nonlinear material absorption, which
      degrades the performance of the angular deflection gates, are considered. Even in
      the presence of realistic absorption, the angular deflection logic gates can
      still produce large-signal gain (>2) sufficient for general logic. Finally, by
      use of a modified gate transfer function approach, these optical logic gates are
      shown to possess large noise margins for robust operation.

PMID- 18324216
TI  - Optical actuation of micromechanical tunneling structures with applications in
      spectrum analysis and optical computing.
AB  - An efficient method for optically actuating a micromechanical cantilever is
      presented for the first time to our knowledge. Measurable responses can be
      obtained for moderate light sources if electron tunneling occurs between the
      cantilever tip and a metallic contact below it. The small deflection of the
      cantilever that is due to light pressure is sufficient then to produce large
      tunneling current variations. On the basis of this effect several applications
      such as a miniaturized spectrum analyzer and one-step optical computing units for
      addition, integration, or differentiation of one-dimensional or two-dimensional
      optical signals are presented.

PMID- 18324217
TI  - Content-addressable data storage by use of volume holograms.
AB  - Data stored as volume holograms--optical interference patterns imprinted into a
      photosensitive storage material--can be accessed both by address and by content.
      An optical correlation-based search compares each input query against all stored
      records simultaneously, a massively parallel but inherently noisy analog process.
      With data encoding and signal postprocessing we demonstrate a holographic content
      addressable data-storage system that searches digital data with high search
      fidelity.

PMID- 18324218
TI  - Encrypted optical storage with wavelength-key and random phase codes.
AB  - An encrypted optical memory system that uses a wavelength code as well as input
      and Fourier-plane random phase codes is proposed. Original data are illuminated
      by a coherent light source with a specified wavelength and are then encrypted
      with two random phase codes before being stored holographically in a
      photorefractive material. Successful decryption requires the use of a readout
      beam with the same wavelength as that used in the recording, in addition to the
      correct phase key in the Fourier plane. The wavelength selectivity of the
      proposed system is evaluated numerically. We show that the number of available
      wavelength keys depends on the correlation length of the phase key in the Fourier
      plane. Preliminary experiments of encryption and decryption of optical memory in
      a LiNbO(3):Fe photorefractive crystal are demonstrated.

PMID- 18324219
TI  - Development and evaluation of the interferometric monitor for greenhouse gases: a
      high-throughput fourier-transform infrared radiometer for nadir earth
      observation.
AB  - The interferometric monitor for greenhouse gases (IMG) was the precursor of the
      high-resolution Fourier-transform infrared radiometer (FTIR) onboard a satellite
      for observation of the Earth. The IMG endured the stress of a rocket launch,
      demonstrating that the high-resolution, high-throughput spectrometer is indeed
      feasible for use onboard a satellite. The IMG adopted a newly developed lubricant
      free magnetic suspension mechanism and a dynamic alignment system for the moving
      mirror with a maximum traveling distance of 10 cm. We present the instrumentation
      of the IMG, characteristics of the movable mirror drive system, and the
      evaluation results of sensor specifications during space operation.

PMID- 18324220
TI  - Description and evaluation of a tropospheric ozone lidar implemented on an
      existing lidar in the southern subtropics.
AB  - Rayleigh-Mie lidar measurements of stratospheric temperature and aerosol profiles
      have been carried out at Reunion Island (southern tropics) since 1993. Since June
      1998, an operational extension of the system is permitting additional
      measurements of tropospheric ozone to be made by differential absorption lidar.
      The emission wavelengths (289 and 316 nm) are obtained by stimulated Raman
      shifting of the fourth harmonic of a Nd:YAG laser in a high-pressure deuterium
      cell. A mosaic of four parabolic mirrors collects the backscattered signal, and
      the transmission is processed by the multiple fiber collector method. The
      altitude range of ozone profiles obtained with this system is 3?17 km. Technical
      details of this lidar system working in the southern tropics, comparisons of
      ozone lidar profiles with radiosondes, and scientific perspectives are presented.
      The significant lack of tropospheric ozone measurements in the tropical and
      equatorial regions, the particular scientific interest in these regions, and the
      altitude range of the ozone measurements to 16?17 km make this lidar supplement
      useful and its adaptation technically conceivable at many Rayleigh-Mie lidar
      stations.

PMID- 18324221
TI  - In situ measurements of optical parameters in Lake Baikal with the help of a
      Neutrino telescope.
AB  - We present results of an experiment performed in Lake Baikal at a depth of
      approximately 1 km. The photomultipliers of an underwater neutrino telescope
      under construction at this site were illuminated by a distant laser. The
      experiment not only provided a useful cross-check of the time calibration of the
      detector but also allowed us to determine inherent optical parameters of the
      water in a way that was complementary to standard methods. In 1997 we measured an
      absorption length of 22 m and an asymptotic attenuation length of 18 m. The
      effective scattering length was measured as 480 m. By use of (cos theta) = 0.95
      (0.90) for the average scattering angle, this length corresponds to a geometric
      scattering length of 24 (48) m.

PMID- 18324222
TI  - Chlorophyll-based model of seawater optical properties.
AB  - A one-parameter model of the inherent optical properties of biologically stable
      waters is proposed. The model is based on the results of in situ measurements of
      inherent optical properties that have been conducted at different seas and oceans
      by a number of researchers. The results of these investigations are processed to
      force this model to agree satisfactorily with an established regression model
      that connects the color index with the chlorophyll concentration. The model
      couples two concentrations of colored dissolved organic matter (concentrations of
      humic and fulvic acids) and two concentrations of suspended scattering particles
      (concentrations of terrigenic and biogenic particles) with the chlorophyll
      concentration. As a result, this model expresses all inherent properties of
      seawater by a single parameter, the concentration of chlorophyll.

PMID- 18324223
TI  - Holographically corrected telescope for high-bandwidth optical communications.
AB  - We present a design for an optical data communications receiver-transmitter pair
      based on the holographic correction of a large diameter, poor-quality, reflecting
      primary mirror. The telescope has a narrow bandwidth (<0.1 nm) with good signal
      frequency isolation (>60 dB) and is scalable to meter-class apertures. We
      demonstrate the correction of a reflector telescope with over 2000 waves of
      aberration to diffraction-limited operation, capable of handling data
      transmission rates up to 100 GHz.

PMID- 18324224
TI  - Two-dimensional index profiling of fibers and waveguides.
AB  - We have constructed a two-dimensional refracted-ray scanner that can resolve
      index-of-refraction increments of approximately 4 x 10(-5). This resolution is an
      order of magnitude finer than the uncertainty of the measurement. The scanner can
      be adapted to evaluate either fibers or planar waveguides. The two-dimensional
      scan and the high precision allow visualization of features, such as deposition
      layers, that are difficult if not impossible to see in conventional one
      dimensional scans.

PMID- 18324225
TI  - Carbon dioxide laser fabrication of fused-fiber couplers and tapers.
AB  - We report the development of a fiber taper and fused-fiber coupler fabrication
      rig that uses a scanning, focused, CO(2) laser beam as the heat source. As a
      result of the pointlike heat source and the versatility associated with scanning,
      tapers of any transition shape and uniform taper waist can be produced. Tapers
      with both a linear shape and an exponential transition shape were measured. The
      taper waist uniformity was measured and shown to be better than +/-1.2%. The rig
      was also used to make fused-fiber couplers. Couplers with excess loss below -0.1
      dB were routinely produced.

PMID- 18324226
TI  - Image formation with regard to object shadow for objects inside a scattering
      medium.
AB  - The conventional theory of image transfer through a scattering medium treats
      objects located upon reflecting surfaces. It is shown that, when an object is
      located inside a scattering medium and shields a part of space, ignoring the
      shadowing leads to incorrect results, especially for modern time-gating systems.
      We develop a general theory of image formation including the shadowing effect
      when an object is located inside a scattering medium. The example of the
      observation of a submerged object through a windy ocean surface is chosen to
      illustrate this theory. A few unexpected effects in imaging of a submerged object
      are found and discussed, including contrast conversion for a sinking object and
      higher contrast in the shadow image than in the image of the object itself. The
      conclusion that using the shadow image for detection of a submerged object can be
      more efficient than using the image of the object itself is of practical
      significance.

PMID- 18324227
TI  - Correlation-based speckle velocimeter with self-mixing interference in a
      semiconductor laser diode.
AB  - We propose a novel self-mixing laser diode speckle velocimeter based on
      autocorrelation. The self-mixing laser diode launches and receives reflected
      light from a moving surface that has a random reflection profile. Some portion of
      the scattered light backcouples into the laser cavity and causes random intensity
      variations in the form of speckle signals. These speckle signals obtained from a
      self-mixing laser diode are processed by use of autocorrelation. The linear
      relation between the velocity and the reciprocal of the correlation time of the
      speckle intensity fluctuations allows us to determine the velocity easily if
      proper calibration is performed. The range of the investigated velocity is 20-450
      mm/s. For an aluminum target that moves at a velocity of 350 mm/s, the
      measurement error is less than 2%.

PMID- 18324228
TI  - Monolithic-integrated microlaser encoder.
AB  - We have developed an extremely small integrated microencoder whose sides are less
      than 1 mm long. It is 1/100 the size of conventional encoders. This microencoder
      consists of a laser diode, monolithic photodiodes, and fluorinated polyimide
      waveguides with total internal reflection mirrors. The instrument can measure the
      relative displacement between a grating scale and the encoder with a resolution
      of the order of 0.01 microm; it can also determine the direction in which the
      scale is moving. By using the two beams that were emitted from the two etched
      mirrors of the laser diode, by monolithic integration of the waveguide and
      photodiodes, and by fabrication of a step at the edge of the waveguide, we were
      able to eliminate conventional bulky optical components such as the beam
      splitter, the quarter-wavelength plate, bulky mirrors, and bulky photodetectors.

PMID- 18324229
TI  - Excess-noise dependence on intracavity aperture shape.
AB  - In lasers with nonorthogonal eigenmodes the excess-noise factor K can be large,
      especially in unstable-cavity lasers with hard-edged intracavity apertures. To
      the best of our knowledge, we report the first detailed study of the dependence
      of K on aperture shape. Calculations and measurements of K for unstable-cavity
      lasers with variable-size apertures of triangular, square, pentagonal, hexagonal,
      octagonal, and rhomboid symmetries are summarized. It is shown that both the
      magnitude of K and its resonant behavior strongly depend on aperture shape and
      that many aspects of this dependence can be explained in terms of one-dimensional
      resonance lengths.

PMID- 18324230
TI  - Ion-exchanged waveguide lasers in Er3+/Yb3+ codoped silicate glass.
AB  - We investigated an Er(3+)/Yb(3+) codoped silicate glass as a host material for
      waveguide lasers operating near 1.5 microm. Spectroscopic properties of the glass
      are reported. Waveguide lasers were fabricated by K(+)-ion exchange from a
      nitrate melt. The waveguides support a single transverse mode at 1.5 microm. An
      investigation of the laser performance as a function of the Yb:Er ratio was
      performed, indicating an optimal ratio of approximately 5:1. Slope efficiencies
      of as great as 6.5% and output powers as high as 19.6 mW at 1.54 microm were
      realized. The experimental results are compared with a waveguide laser model that
      is used to extract the Er(3+) upconversion coefficients and the Yb(3+)-Er(3+)
      cross-relaxation coefficients. The results indicate the possibility of obtaining
      high-performance waveguide lasers from a durable silicate host glass.

PMID- 18324231
TI  - Design of polarization-selective diffractive phase elements in a laser cavity.
AB  - We report a new design for a polarization-selective laser cavity with
      birefringent diffractive phase elements. This laser cavity can create two modes
      with different polarizations and profiles launched separately from two end
      mirrors. The numerical simulation results show that the constructed laser cavity
      can successfully generate two orthogonal polarization modes with a uniform
      circular shaped pattern output from one end mirror and a uniform square-shaped
      pattern output from another end mirror.

PMID- 18324232
TI  - Crack arrest and stress dependence of laser-induced surface damage in fused
      silica and borosilicate glass.
AB  - Results of experiments on stress-inhibited laser-driven crack growth and stress
      delayed laser-damage initiation thresholds in fused silica, borosilicate glass
      (BK-7), and cleaved bulk silica are presented. A numerical model is developed to
      explain the crack arrest in fused silica. Good agreement is obtained between the
      model and a finite-element code. The crack arrest is demonstrated to be the
      result of the breaking of a hoop-stress symmetry that is responsible for crack
      propagation in fused silica.

PMID- 18324233
TI  - Kilohertz pulse repetition frequency slab Ti:sapphire lasers with high average
      power (10 W).
AB  - High-average-power broadband 780-nm slab Ti:sapphire lasers, pumped by a
      kilohertz pulse repetition frequency copper vapor laser (CVL), were demonstrated.
      These lasers are designed for damage-free power scaling when pumped by CVL's
      configured for maximum output power (of order 100 W) but with poor beam quality
      (M(2) approximately 300). A simple Brewster-angled slab laser side pumped by a
      CVL produced 10-W average power (1.25-mJ pulses at 8 kHz) with 4.2-ns FWHM pulse
      duration at an absolute efficiency of 15% (68-W pump power). Thermal lensing in
      the Brewster slab laser resulted in multitransverse mode output, and pump
      absorption was limited to 72% by the maximum doping level for commercially
      available Ti:sapphire (0.25%). A slab laser with a multiply folded zigzag path
      was therefore designed and implemented that produced high-beam-quality (TEM(00)
      mode) output when operated with cryogenic cooling and provided a longer
      absorption path for the pump. Excessive scattering of the Ti:sapphire beam at the
      crystal surfaces limited the efficiency of operation for the zigzag laser, but
      fluorescence diagnostic techniques, gain measurement, and modeling suggest that
      efficient power extraction (>15 W TEM(00), >23% efficiency) from this laser would
      be possible for crystals with an optical quality surface polish.

PMID- 18324234
TI  - Flame flow tagging velocimetry with 193-nm H2O photodissociation.
AB  - In a new nonintrusive, instantaneous flow tagging method called hydroxyl tagging
      velocimetry (HTV), a molecular grid of hydroxyl (OH) radicals is written into a
      flame and the displaced grid is imaged at a later time to give the flame's
      velocity profile. Single-photon photodissociation of vibrationally excited H(2)O,
      when a 193-nm ArF excimer laser is used, produces a tag line of superequilibrium
      OH and H photoproducts in a high-temperature flow field that itself may contain
      ambient OH. The tag line OH concentration is composed mostly of direct OH
      photoproducts, but OH is also indirectly produced through H photoproduct
      reactions with oxygen-bearing species. For lean and modestly rich flames the OH
      tag lifetime is of the order of 1 ms. For very rich H(2)-air flames (equivalence
      ratio of 4.4) the lifetime drops to 200 ns. After displacement the position of
      the OH tag line is revealed through fluorescence caused by OH (A-X) (3 <-- 0)
      excitation by using a 248-nm tunable KrF excimer laser. A HTV grid of multiple
      tag lines, providing multipoint velocity information, is experimentally
      demonstrated in a turbulent H(2)/N(2)-air diffusion flame.

PMID- 18324235
TI  - Retrieval and monitoring of aerosol optical thickness over an urban area by
      spaceborne and ground-based remote sensing.
AB  - We used an instrumental synergy of both ground-based (sunphotometer) and
      spaceborne [POLDER (polarization and directionality of the Earth's reflectances)
      and Meteosat] passive remote-sensing devices to determine the aerosol optical
      thickness over the suburban area of Thessaloniki, Greece, from April 1996 to June
      1997. The POLDER spaceborne instrument measures the degree of polarization of the
      solar radiance reflected by the Earth-atmosphere system. Aerosol optical
      thickness (AOT) retrieval needs an accurate estimate of the contribution of the
      ground surface to the top of atmosphere's polarized radiance. We tested existing
      surface reflectance models and fitted their parameters to find the best model for
      the Thessaloniki area. The model was constrained and validated by use of
      independent data sets of coincident sunphotometer and POLDER measurements. The
      comparison indicated that the urban AOT over Thessaloniki was retrieved by the
      POLDER instrument with an accuracy of +/-0.05. From analysis of Meteosat data we
      found that approximately 40% of the days with high AOT (>0.18) are associated
      with African dust transport events, all observed in the period March-July.
      Excluding dust events, the 15-month AOT averages 0.12 +/- 0.04. During the 15
      month period that the study was conducted, we observed aerosol pollution peaks
      with an AOT of >0.24 on 15 of the 164 days on which measurements were possible.

PMID- 18324236
TI  - Autonomous beam alignment for coherent Doppler lidar with multielement detectors.
AB  - Autonomous beam alignment for coherent Doppler lidar requires accurate
      information about optical misalignment and optical aberrations. A multielement
      heterodyne detector provides the required information without a loss in overall
      system performance. The effects of statistical variations from the random
      backscattered field (speckle field) are determined with computer simulations for
      both ground-based operation with a fixed calibration target and for space-based
      operation with random target backscatter.

PMID- 18324237
TI  - Shock-tube study of high-pressure H2O spectroscopy.
AB  - Water-vapor absorption features near 7117, 7185, and 7462 cm(-1) were probed at
      pressures to 65 atm (1 atm = 760 Torr) and temperatures to 1800 K in shock-heated
      mixtures of H(2)O in N(2) and Ar with a diode-laser source. Calculated
      absorbances based on Voigt line shapes and measured line parameters were in good
      agreement, within 10%, with measured absorbances at 7185.4 and 7117.4 cm(-1). We
      obtained temperature-dependent N(2) and Ar shift parameters for H(2)O absorption
      features by shifting the calculated spectra to match the recorded absorption
      scan. Absorbance simulations based on line parameters from HITRAN and HITEMP were
      found to be similar over the range of temperatures 600-1800 K and were within 25%
      of the measurements. The combined use of Toth's [Appl. Opt. 36, 4851 (1994)] line
      positions and strengths and HITRAN broadening parameters resulted in calculated
      absorption coefficients that were within 15% of the measurements at all three
      probed wavelengths.

PMID- 18324238
TI  - Experimental investigation of saturated degenerate four-wave mixing for
      quantitative concentration measurements.
AB  - Degenerate four-wave mixing (DFWM) line shapes and signal intensities are
      measured experimentally in well-characterized hydrogen-air flames operated over a
      wide range of equivalence ratios. We use both low (perturbative) and high
      (saturating) beam intensities in the phase-conjugate geometry. Resonances in the
      A 2Sigma+ -X 2II (0,0) band of OH are probed with multiaxial-mode laser
      radiation. The effects of saturation on the line-center signal intensity and the
      resonance linewidth are investigated. The DFWM signal intensities are used to
      measure OH number densities in a series of near-adiabatic flames at equivalence
      ratios ranging from 0.5 to 1.5. Use of saturating pump intensities minimizes the
      effects of beam absorption, providing more-accurate number density measurements.
      The saturated DFWM results are in excellent agreement with OH absorption
      measurements and equilibrium calculations of OH number density. The polarization
      dependence of the P(1)(2) and R(2)(1) resonances is investigated in both laser
      intensity regimes. There is a significant change in relative reflectivities for
      different polarization configurations when saturated.

PMID- 18324239
TI  - High-frequency-stability diode-pumped Nd:YAG lasers with the FM sidebands method
      and Doppler-free iodine lines at 532 nm.
AB  - The FM spectroscopy technique has been applied to two frequency-doubled Nd:YAG
      lasers to achieve absolute frequency stabilization against the hyperfine
      structure components of the rovibronic P(54) 32-0 iodine line at 532 nm. A
      fractional frequency stability of 2 x 10(-13) tau(-1/2) has been obtained for
      integration times in the range of 1 ms < tau < 10 s. For longer integration times
      the stability level remains below 10(-13), reaching a minimum value of 4.6 x 10(
      14) at 100 s. This high stability level is, to our knowledge, the best value
      achieved against iodine lines by this locking method and for a fully
      transportable system.

PMID- 18324241
TI  - Modeling and design of planar slanted volume holographic gratings for wavelength
      division-multiplexing applications.
AB  - Holographic gratings are modeled and designed for path-reversed substrate-guided
      wave wavelength-division demultiplexing (WDDM) as a continuation of earlier
      research [Appl. Opt. 38, 3046 (1999)]. An efficient and practical method is
      developed to simulate the slanted volume holographic gratings. The trade-off
      between dispersion and the bandwidth of the holograms is analyzed. A 60 degrees
      (incident angle of the grating)/60 degrees (diffraction angle of the grating in
      air) grating structure is selected to demultiplex optical signals in the 1555-nm
      spectral region, and a 45 degrees /45 degrees grating structure is chosen for the
      spectral region near 800 nm. Experimental results are consistent with the
      simulation results for these two WDDM devices. A four-channel WDDM is also
      demonstrated at a center wavelength of 1555 nm and with a channel spacing of 2
      nm.

PMID- 18324242
TI  - Characteristics of grating-assisted couplers.
AB  - Characteristics of grating-assisted coupling between two parallel waveguides are
      analyzed. The influence of the grating parameters, such as groove depth, duty
      cycle, and refractive indices is considered. Chirped and parallel gratings as
      well as gratings with sinusoidal envelope periodicity are also addressed. The
      analysis is based on a unified coupled-mode formalism, with the transfer-matrix
      method as a general solution technique. It is shown how to modify the grating
      parameters to provide a specific spectral response (reflectivity and transmission
      coefficients). As an example, two parallel gratings are used to obtain a similar
      response to a single grating of double length. The location of the grating
      between the two waveguides as well as the light-wave injection direction are very
      important. The presented methods and effects may be useful for design and
      analysis in the fields of optical communications, sensing, and processing.

PMID- 18324243
TI  - Simultaneous amplitude-contrast and quantitative phase-contrast microscopy by
      numerical reconstruction of Fresnel off-axis holograms.
AB  - We present a digital method for holographic microscopy involving a CCD camera as
      a recording device. Off-axis holograms recorded with a magnified image of
      microscopic objects are numerically reconstructed in amplitude and phase by
      calculation of scalar diffraction in the Fresnel approximation. For phase
      contrast imaging the reconstruction method involves the computation of a digital
      replica of the reference wave. A digital method for the correction of the phase
      aberrations is presented. We present a detailed description of the reconstruction
      procedure and show that the transverse resolution is equal to the diffraction
      limit of the imaging system.

PMID- 18324244
TI  - Implementation of multilens micro-optical systems with large numerical aperture
      by stacking of microlenses.
AB  - In the field of micro-optics there is a demand for objectives with large
      numerical aperture (NA). One example is optical storage in which a NA greater
      than 0.5 is required. For planar microlenses the NA is determined by means of the
      maximal index difference and the degree of exchange and reaches typical values of
      0.13-0.2. Thus stacking is needed to build high NA objectives from planar
      microlenses. An additional benefit of stacking lenses is the possibility to
      correct for different types of aberrations. We realized two stacked systems: an
      array of micro-objectives with a NA of 0.45 from three microlens arrays and a
      confocal sensor head from four microlens arrays and one pinhole array mask.

PMID- 18324245
TI  - Flux spatial emission obtained from technical specifications for a general
      filament light source.
AB  - A new, to our knowledge, method for evaluating three-dimensional flux
      distributions for general filament light sources is presented. The main
      advantages of the developed model are its generality and its simplicity. From
      plots of the emitted luminous intensity, usually provided by the lamp's
      manufacturer, in three orthogonal planes a detailed account is given of how to
      establish flux emission from the light source in any direction. The method
      involves a selective smoothing procedure, a curve-fitting step, and a final
      interpolation. A full model is developed for a typical commercial filament bulb
      (Philips, Model P21W Inco K) that is quite common in many industrial
      applications. A fourth intensity plot, usually provided by the lamp's
      manufacturer, is used to validate the model. To confirm the validity of the model
      further, we present an industrial application (the photometric simulation of a
      car taillight) that uses the modeled Philips Model P21W source. A comparison
      between simulated data obtained by use of the developed P21W model and measured
      results at our industrial partner's laboratories reinforces the proposed source
      model.

PMID- 18324246
TI  - Generalized algorithm for photoelastic measurements based on phase-stepping
      imaging polarimetry.
AB  - A general method for measuring the birefringence of nondichroic, linear retarder
      media has been presented. The method is based on phase-stepping imaging
      polarimetry and permits the azimuth angle, phase retardation, and transmission
      coefficient of a sample to be calculated. The method uses a simple setup, a
      sample at rest, and permits fast acquisition of data. With the mathematical
      description applied, various algorithms for different optical configurations can
      be used and any number of intensity patterns can be generated. Experimental
      results for photoelastic samples and the results of measurements of the
      birefringence of optical components and biological samples are also presented.

PMID- 18324247
TI  - Analysis of a low-finesse Fabry-Perot sensing interferometer illuminated by a
      multimode optical fiber.
AB  - A model of the reflected fringe system for an ideal plane-parallel, low-finesse
      Fabry-Perot (FP) cavity illuminated by a multimode optical fiber has been
      developed and experimentally validated. This showed that the phase dispersion
      within the cavity arising from the divergent nature of the incident illumination
      significantly degrades the visibility of the reflected fringes. Departures from
      the ideal FP cavity are also examined. The effect on fringe visibility when the
      plane of the FP cavity is tilted with respect to the fiber axis and when the
      cavity surfaces are no longer perfectly parallel to each other has been explored.
      The analysis described is relevant to the design and the optimization of
      multimode optical-fiber sensors that use FP sensing cavities.

PMID- 18324248
TI  - Intercalibration of SUMER and CDS on SOHO. I. SUMER detector A and CDS NIS.
AB  - The results of an intercalibration between the extreme ultraviolet spectrometers
      Coronal Diagnostic Spectrometer (CDS) and Solar Ultraviolet Measurements of
      Emitted Radiation (SUMER) onboard the Solar and Heliospheric Observatory (SOHO)
      are presented. During the joint observing program Intercal_01, CDS and SUMER were
      pointed at the same locations in quiet Sun areas and observed in the same
      wavelength bands located around the spectral lines He i 584 A, Mg x 609 A, and Mg
      x 624 A. The data sets analyzed here consist of raster images recorded by the CDS
      normal-incidence spectrometer and SUMER detector A and span the time from March
      1996 to August 1996. Effects of the different spatial and spectral resolutions of
      both instruments have been investigated and taken into account in the analysis.
      We find that CDS measures generally a 30% higher intensity than SUMER in the He i
      584-A line, while it measures 9% and 17% higher intensities in Mg x 609 A and Mg
      x 624 A, respectively. Both instruments show very good temporal correlation and
      stability, indicating that solar variations dominate over changes in instrumental
      sensitivity. Our analysis also provides in-flight estimates of the CDS spatial
      point-spread functions.

PMID- 18324249
TI  - Domain-engineered pyroelectric radiometer.
AB  - We built a large-area domain-engineered pyroelectric radiometer with high spatial
      and spectral response uniformity that is an excellent primary transfer standard
      for measurements in the near- and the mid-infrared wavelength regions. The domain
      engineering consisted of inverting the spontaneous polarization over a 10-mm
      diameter area in the center of a uniformly poled, 15.5 mm x 15.5 mm square, 0.25
      mm-thick LiNbO(3) plate. Gold black was used as the optical absorber on the
      detector surface, and an aperture was added to define the optically sensitive
      detector area. Our results indicate that we significantly reduced the acoustic
      sensitivity without loss of optical sensitivity. The detector noise equivalent
      power was not exceptionally low but was nearly constant for different acoustic
      backgrounds. In addition, the detector's spatial-response uniformity variation
      was less than 0.1% across the 7.5-mm-diameter aperture, and reflectance
      measurements indicated that the gold-black coating was spectrally uniform within
      2%, from 800 to 1800 nm. Other detailed evaluations of the detector include
      detector responsivity as a function of temperature, electrical frequency
      response, angular response, and field of view.

PMID- 18324250
TI  - Simultaneous three-dimensional dynamic deformation measurements with pulsed
      digital holography.
AB  - The three deformation components x, y, z of a vibrating object are measured
      simultaneously by use of digital holography with a double-pulse ruby laser
      source. The object is illuminated from three different directions, each optically
      path matched with three reference beams such that three independent digital
      holograms are formed and added incoherently in one single CCD image. The optical
      phase difference between the two recordings taken for each hologram is
      quantitatively evaluated by the Fourier-transform method so that a set of three
      phase maps is obtained, representing the deformation along three sensitivity
      vectors. The total object deformation is obtained as a vector resultant from the
      data of the three phase maps. To give the full three-dimensional (3-D)
      description, the shape of the object is measured by the two-wavelength contouring
      method. Experiments are performed with a cylinder as the test object, transiently
      and harmonically excited. The 3-D deformation and shape measurement results are
      presented graphically.

PMID- 18324251
TI  - Optical frequency-domain imaging microprofilometry with a frequency-tunable
      liquid-crystal Fabry-Perot etalon device.
AB  - An optical frequency-domain interference microscope with a liquid-crystal Fabry
      Perot interferometer as an optical frequency-scan device was developed for
      microscopic three-dimensional shape measurements. The proposed system can perform
      absolute measurement of the discontinuous surface profile of a microscopic object
      without use of mechanically moving components such as a piezoelectric transducer
      or a grating spectrometer. Experimental results are presented that demonstrate
      the validity of the principle.

PMID- 18324252
TI  - Laser-diode interferometer with a photothermal modulation.
AB  - A laser-diode (LD) interferometer that uses an accurate photothermal-modulating
      technique is proposed. Since this technique with the photothermal method
      modulates only a wavelength of the LD, measurement accuracy is not affected by an
      intensity modulation that usually appears in the current modulation. The
      fundamental characteristics of this technique are investigated in detail. The new
      setup is tested, and its accuracy is compared with that of a previous system.

PMID- 18324253
TI  - Scanning delay line with a rotating-parallelogram prism for low-coherence
      interferometry.
AB  - We describe a fast scanning optical delay line for low-coherence interferometry
      that has good linearity, a high duty cycle, and a continuously adjustable scan
      range. The delay line consists of a rotating-parallelogram prism with the
      rotation axis tilted with respect to the incident beam and two motionless
      mirrors. The delay line is well suited for nearly simultaneous distance
      measurements at two different depths, which is useful for making absolute and
      differential distance measurements.

PMID- 18324254
TI  - Simple method of measuring scattering losses in optical fibers.
AB  - A simple method of measuring the scattering losses of optical fibers was
      developed. The method permits the measurement of the scattering-loss spectra by
      use of photon counting. Measurement is based on right-angle scattering, which is
      dominated by Rayleigh scattering, a material-intrinsic loss. A reference fiber
      for which the scattering loss is known is used to cancel out the unknown factors
      that are dependent on the optical setup. The scattering-loss measurement was
      demonstrated by use of two different low-loss fibers and was found to agree with
      predetermined figures to within 10% over the wavelength range 0.44-1.0 microm.
      Finally, the method was applied to a new high-numerical-aperture optical fiber to
      find its material scattering loss.

PMID- 18324255
TI  - Improved three-dimensional imaging with a digital holography microscope with a
      source of partial spatial coherence.
AB  - A digital holographic technique is implemented in a microscope for three
      dimensional imaging reconstruction. The setup is a Mach-Zehnder interferometer
      that uses an incoherent light source to remove the coherent noise that is
      inherent in the laser sources. A phase-stepping technique determines the optical
      phase in the image plane of the microscope. Out-of-focus planes are refocused by
      digital holographic computations, thus considerably enlarging the depth of
      investigation without the need to change the optical focus mechanically. The
      technique can be implemented in transmission for various magnification ratios and
      can cover a wide range of applications. Performances and limitations of the
      microscope are theoretically evaluated. Experimental results for a test target
      are given, and examples of two applications in particle localization and
      investigation of biological sample are provided.

PMID- 18324256
TI  - Static tester for characterization of phase-change, dye-polymer, and magneto
      optical media for optical data storage.
AB  - We have designed and built a static tester around a commercially available
      polarized light microscope. This device employs two semiconductor laser diodes
      (at 643- and 680-nm wavelengths) for the purpose of recording small marks on
      various media for optical data storage and for the simultaneous monitoring of the
      recording process. We use one of the lasers in the single-pulse mode to write a
      mark on the sample and operate the other laser in the cw mode to monitor the
      recording process. The two laser beams are brought to coincident focus on the
      sample through the objective lens of the microscope. The reflected beams are sent
      through a polarizing beam splitter and thus divided into two branches, depending
      on whether they are p or s polarized. In each branch the beam is further divided
      into two according to the wavelength. The four beams thus produced are sent to
      four high-speed photodetectors, and the resulting signals are used to monitor the
      reflectance as well as the polarization state of the beam on reflection from the
      sample. We provide a comprehensive description of the tester's design and
      operating principles. We also report preliminary results of measurements of phase
      change, dye-polymer, and magneto-optical samples, which are currently of interest
      in the areas of writable and rewritable optical data storage.

PMID- 18324257
TI  - Visible-band testbed projector with a replicated diffractive optical element.
AB  - Raytheon has designed, fabricated, and tested a diffractive-optical-element-based
      (DOE-based) testbed projector for direct and indirect visual optical
      applications. By use of a low-cost replicated DOE surface from Rochester
      Photonics Corporation for color correction the projector optics bettered the
      modular transfer function of an equivalent commercial camera lens. The testbed
      demonstrates that a practical DOE-based optical system is suitable for both
      visual applications (e.g., head-mounted displays) and visual projection (e.g.,
      tactical sensors). The need for and the proper application of DOE's in visual
      optical systems, the nature and the performance of the projector optical design,
      and test results are described.

PMID- 18324258
TI  - Vacuum temperature-dependent ellipsometric studies on WO3 thin films.
AB  - Vacuum temperature-dependent ellipsometric studies on WO(3) thin films are
      reported at a single wavelength, lambda = 0.633 microm, and across a temperature
      range of 100 < T <or= 453 K. All the measurements were made in an optical
      cryostat fixed in the sample compartment of the ellipsometer. Experimental
      results involving reduction and oxidation of WO(3) are discussed in terms of
      electrochromic characteristics and structural changes, which can be helpful for
      many and various technological applications. Temperature-dependent drifts in the
      real part of the refractive index n and extinction coefficient k have been
      explained by use of a variety of chemical relations and have also been utilized
      to evaluate their temperature coefficients. Moreover, polaronic excitations
      between localized states around the Fermi level are put forward to explain the
      ellipsometric results at or above room temperature, and both polaronic and
      bipolaronic transitions are proposed for interpreting low-temperature
      ellipsometric measurements.

PMID- 18324259
TI  - Deep nulling of visible laser light.
AB  - Nulling interferometry, a proposed technique for dimming a star relative to its
      surroundings by destructively interfering the light collected by two individual
      telescopes [Bracewell, Nature 274, 780-781 (1978); Shao and Colavita, Ann. Rev.
      Astron. Astrophys. 30, 457-498 (1992)], has the potential to permit the direct
      detection of nearby extrasolar planets. However, because of the extremely high
      degree of symmetry required for useful levels of starlight nulling, the technique
      remains in its infancy. We present results of laboratory experiments with a
      rotational shearing interferometer that are aimed at demonstrating the
      feasibility of deep nulling at the levels needed for direct planet detection. Our
      first results include the successful nulling of red laser light to a part in
      10(5) and the stabilization of the null leakage to a part in 10(4).

PMID- 18324260
TI  - Slit-scanning confocal microendoscope for high-resolution in vivo imaging.
AB  - We discuss the design and construction of a novel imaging system in which a fiber
      optic imaging bundle and miniature optical and mechanical components are used to
      allow confocal fluorescence microscopy in remote locations. The instrumentation
      has been developed specifically for cellular examination of tissue for optical
      biopsy. Miniaturization of various components makes the device usable in a
      clinical setting. The numerical aperture of the beam in the tissue is 0.5, and
      the field of view is 430 microm. The measured lateral resolution of the system is
      3.0 microm. The axial point and the axial planar response functions of the
      confocal system were measured with a FWHM of 10 and 25 microm, respectively. In
      vitro and in vivo images obtained with cell cultures, human tissue specimens, and
      animal models indicate that the performance of the device is adequate for
      microscopic evaluation of cells.

PMID- 18324261
TI  - Frequency doubling of ultrashort laser pulses in biological tissues.
AB  - Theoretical and experimental studies of second-harmonic generation (SHG) in
      biological tissues was performed by use of ultrashort laser pulses (<1 ps). A
      simplified one-dimensional model for the generation and the propagation of
      frequency-doubled light inside tissue was developed. This model was tested in
      vitro against measurements of pig and chicken tissue and human tooth. The
      experimental results indicate that the intensity of SHG varies significantly
      among tissue types and between test sites in individual tissue. Possibilities of
      using this nonlinear tissue property in imaging and diagnostics are discussed.

PMID- 18324262
TI  - Very-high-speed all-optical code-division multiplexing systems using a 2n prime
      code.
AB  - We demonstrate experimental all-optical code-division multiplexing (AO-CDM)
      systems using 64-ps optical pulses and a 2" prime code of n = 3. A distinguishing
      feature of this experiment is that the modulation of an ultrashort optical clock
      stream by electrical data is realized without using any optical intensity
      modulator at each transmitter. Moreover, only low-cost optical 2 x 2 couplers and
      fiber delay lines are employed to implement all-serial encoders and decoders for
      a 2n prime code.

PMID- 18324263
TI  - A novel technique to measure laser beam spot sizes.
AB  - In this letter we report a novel technique to measure small laser beam spot
      sizes. We use the open aperture z-scan technique as a tool to measure the laser
      beam spot size. This technique measures small spot sizes with accuracy better
      than 10%.

PMID- 18324264
TI  - Optical grating diffraction method: from strain microscope to strain gauge.
AB  - The grating diffraction method for direct strain measurement is reviewed. Two
      systems which use this method are presented. The first system is a compact strain
      microscope. A Leitz optical transmitting microscope with white light source is
      reconstructed by developing a loading and recording system. Gratings with median
      density of between 40 and 200 lines/mm are used. With the help of a Bertrand
      lens, the Fourier spectrum of the grating is formed with high image quality on
      the CCD sensor plane. Software is developed to precisely, quickly and
      automatically determine the diffraction spot centroids. The second system is a
      new strain sensor based on a high-frequency grating and two Position Sensor
      Detectors (PSDs). The grating, attached to the surface of the specimen, is
      illuminated by a focused laser beam, generally with a frequency of 1,200
      lines/mm. The centroids of diffracted beam spots from the grating are
      automatically determined using two PSD sensors connected to a personal computer.
      The shift of diffracted beam spots due to specimen deformation is detected.
      Strain sensitivity of one micro-strain can be obtained, as can a 0.4 mm spatial
      resolution for strain measurement. The system can be used for both static and
      dynamic tests.

PMID- 18324265
TI  - Color dynamics of diffraction gratings: evaluation and applications in optical
      security.
AB  - We looked for design methodologies that cope with optical specifications
      described in terms of trajectories in the CIE (Commission Internationale de
      l'Eclairage) 1976 chromaticity diagram in the context of low-cost mass
      reproduction processes that inevitably introduce changes in the design of a
      diffractive device for security applications. The mathematics of the design
      process can be strongly simplified if the theory of planar waveguides (in
      integrated optics) is used to estimate, with sufficient accuracy, the position of
      Wood singularities, responsible for the more-interesting visual features of a
      grating. We show how to use such a model to assess color dynamics variations that
      are due to production and to estimate domains within the space of grating
      parameters that enable both first- and second-level security features to be
      implemented simultaneously. All the results are compared with the values obtained
      by rigorous coupled-wave analysis.

PMID- 18324266
TI  - Stripe color separation with diffractive optics.
AB  - We describe a color separation optical element with potential display
      applications that is designed to separate light into an array of red, green, and
      blue stripes formed at a certain distance from the component. The stripe color
      separation grating is a surface-relief diffractive optical element composed of a
      repeated pattern of three constituent gratings. We describe the design principles
      and a numerical analysis of the component, showing that a maximum theoretical
      efficiency with which the colors are directed into the stripes is approximately
      80%. We also examine the dependence of the efficiency on the grating feature
      size. In addition, we report on the fabrication of four of these components,
      using a combination of electron-beam lithography and photolithography with a
      backexposure technique. Measurements are presented to show the color separation
      property.

PMID- 18324267
TI  - Infrared femtosecond laser pulse-induced three-dimensional bright and long
      lasting phosphorescence in a Ce3+-doped Ca2Al2SiO7 crystal.
AB  - We report on three-dimensional bright and long-lasting phosphorescence in a
      Ce(3+)-doped Ca(2)Al(2)SiO(7) crystal. After we scan with a focused 800-nm
      femtosecond pulsed laser, the path traversed by the focal point of the laser in
      the crystal emits bright and long-lasting phosphorescence that can be seen with
      the naked eye in the dark even 10 h after the removal of the activating laser.
      Absorption spectra of the crystal show that defect centers have formed after the
      laser irradiation, and the absorption that is due to the defect centers decays
      with time. It is suggested that a mechanism of the long-lasting phosphorescence
      consists of a thermostimulated recombination of holes and electrons at traps
      induced by the laser irradiation at room temperature.

PMID- 18324268
TI  - Pentagon-shaped 0 degrees -cut BaTiO3 as an efficient self-pumped phase
      conjugator.
AB  - A pentagon-shaped 0 degrees-cut undoped BaTiO(3) crystal was used to construct a
      high-quality self-pumped phase conjugator. The conjugator shows a steady phase
      conjugate output with a high reflectivity (as high as approximately 68%), a fast
      rising time, and a large angular range of acceptance. It also shows a good
      fidelity in the phase-conjugate reconstructed image; the resolution reaches 17
      microm.

PMID- 18324269
TI  - Dark self-enhancement in dichromated poly(vinyl alcohol) gratings: a detailed
      study.
AB  - Experimental results concerning the real-time hologram recording process in
      dichromated poly(vinyl alcohol) are presented. Self-enhancement, the increase in
      diffraction efficiency of the holographic gratings in the dark after recording,
      is also presented. The influence of the recording parameters (pH, exposure
      energy, dichromate concentration) on the self-enhancement gain is shown. Maximum
      gain was 6, and self-enhancement occurred during the 3 days following the
      exposure. The results and a model for the reduction of chromium ions
      corresponding to the formation of the grating are discussed.

PMID- 18324270
TI  - Dark self-enhancement in dichromated-gelatin gratings: a detailed study.
AB  - Strong dark self-enhancement, the increase in diffraction efficiency after
      irradiation, has been reported previously for dichromated-gelatin gratings. Here
      a more-detailed study of this self-enhancement effect is presented. The self
      enhancement in dichromated-gelatin gratings was of the order of 10-100, depending
      on the pH and on the dichromate concentration of the solution used for the
      preparation of dichromated-gelatin films. The highest self-enhancement gain
      occurred when pH was high and dichromate concentration was low. The increase in
      the diffraction efficiencies of the gratings continued over 3 months.

PMID- 18324271
TI  - Illumination-invariant pattern recognition with joint-transform-correlator-based
      morphological correlation.
AB  - The performance of nonlinear morphological correlation is investigated and
      compared with that of conventional linear correlation. In particular, the effects
      of illumination variations on the morphological correlation output are
      investigated in detail. The morphological correlation is shown to be invariant to
      uniform input-image illumination when the input-image illumination is higher than
      that of the reference. It also provides higher pattern discriminability, sharper
      peaks, and more-robust detection in the presence of salt-and-pepper noise than
      does the linear correlation. Computer-simulation results are provided.

PMID- 18324272
TI  - Color pattern recognition in white-light joint transform correlation.
AB  - We first discuss the restriction on the incoherent source and the color filters
      in a joint transform correlation (JTC) system for white-light color pattern
      recognition and then report on a novel, to our knowledge, solution of channeling
      in a white-light JTC system, using a tricolor grating to encode the color
      patterns in real time. The theoretical analyses and the experimental results show
      not only that the restriction on the experimental condition is relieved but also
      that parallel channeling of the power spectra of the encoded pattern is easily
      performed. In addition, the zero-order power spectrum also forms a useful channel
      for the shape-only correlation.

PMID- 18324273
TI  - Superresolving optical system with time multiplexing and computer decoding.
AB  - Objects that have slow temporal variations may be superresolved with two moving
      masks such as pinhole or grating. The first mask is responsible for encoding the
      input image, and the second one performs the decoding operation. This approach is
      efficient for exceeding the resolving capability beyond Abbe's limit of
      resolution. However, the proposed setup requires two physical gratings that
      should move in a synchronized manner. We propose what is believed to be a novel
      configuration in which the second grating responsible for the information
      decoding is replaced with a detector array and some postprocessing digital
      procedures. In this way the synchronization problem that exists when two gratings
      are used is simplified. Experimental results are provided for illustrating the
      utility of the new approach.

PMID- 18324274
TI  - Extreme-ultraviolet phase-shifting point-diffraction interferometer: a wave-front
      metrology tool with subangstrom reference-wave accuracy.
AB  - The phase-shifting point-diffraction interferometer (PS/PDI) was recently
      developed and implemented at Lawrence Berkeley National Laboratory to
      characterize extreme-ultraviolet (EUV) projection optical systems for
      lithography. Here we quantitatively characterize the accuracy and precision of
      the PS/PDI. Experimental measurements are compared with theoretical results. Two
      major classes of errors affect the accuracy of the interferometer: systematic
      effects arising from measurement geometry and systematic and random errors due to
      an imperfect reference wave. To characterize these effects, and hence to
      calibrate the interferometer, a null test is used. This null test also serves as
      a measure of the accuracy of the interferometer. We show the EUV PS/PDI, as
      currently implemented, to have a systematic error-limited reference-wave accuracy
      of 0.0028 waves (lambda/357 or 0.038 nm at lambda = 13.5 nm) within a numerical
      aperture of 0.082.

PMID- 18324275
TI  - Comparison of fully three-dimensional optical, normally conducting, and
      superconducting interconnections.
AB  - Several approaches to three-dimensional integration of conventional electronic
      circuits have been pursued recently. To determine whether the advantages of
      optical interconnections are negated by these advances, we compare the
      limitations of fully three-dimensional systems interconnected with optical,
      normally conducting, repeatered normally conducting, and superconducting
      interconnections by showing how system-level parameters such as signal delay,
      bandwidth, and number of computing elements are related. In particular, we show
      that the duty ratio of pulses transmitted on terminated transmission lines is an
      important optimization parameter that can be used to trade off signal delay and
      bandwidth so as to optimize applicable measures of performance or cost, such as
      minimum message delay in parallel computation.

PMID- 18324276
TI  - Discrete correlation processor as a building core of a digital optical computing
      system: architecture and optoelectronic embodiment.
AB  - In this paper we present a general-purpose discrete correlation processor (DCP)
      expected to be the building core block of a digital optical computing system. The
      DCP-1 is embodied by optoelectronic devices such as a VCSEL and a complementary
      metal-oxide silicon photodetector. The application targets of the DCP-1 are
      optical interconnection and various types of digital optical computing. It is
      expected that digital optical computing techniques coupled with the
      optoelectronic technology will provide large capability and flexibility in
      information processing. Introduction of a processing scheme of optical array
      logic enlarges the applicable field of the DCP-1 as well as its processing
      capability. With the experimental DCP-1 a bit error rate smaller than 10(-9) was
      obtained for A . B? operation under a 500-kHz clock rate.

PMID- 18324277
TI  - Topographical evaluation of optical disks with polycarbonate substrates in the
      manufacturing process.
AB  - An optical contour mapping with a laser-interference method was carried out to
      evaluate the topographical deformation of optical memory disks. The dynamics of
      the deformation in a manufacturing process was studied. Reflective films and a
      protective resin coating increased the dishing, irrespective of the original
      shape of a substrate. A bonding process decreased the dishing and contributed to
      mechanical stability that lasted for a long period in daily use. In the case of a
      0.6-mm-thick substrate, as with a DVD disk, the large dishing of the single
      substrate was suppressed by the bonding to less than 100 microm. In addition, it
      was shown that distortions arising from the molding process remained in the final
      product and that the initial process should be carefully controlled.

PMID- 18324278
TI  - Encrypted optical storage with angular multiplexing.
AB  - We present the first, to our knowledge, demonstration of an encrypted optical
      storage based on double-random phase encoding by using angular multiplexing in a
      photorefractive material. Original two-dimensional data are encrypted by use of
      two random phase codes located in the input and the Fourier planes and are then
      stored holographically in a LiNbO(3):Fe crystal. The retrieval of the original
      data can be achieved with a phase-conjugated readout scheme. We demonstrate the
      encryption and the decryption of multiple frames of two-dimensional digital data
      by using angular multiplexing. We also evaluate numerically the influence of the
      bandwidth of the optical system on the decrypted digital data. The bit error rate
      as a function of the optical system bandwidth is presented.

PMID- 18324279
TI  - Simultaneous retrieval of aerosol refractive index and particle size distribution
      from ground-based measurements of direct and scattered solar radiation.
AB  - Ground-based sunphotometer observation of direct and scattered solar radiation is
      a traditional tool for providing data on aerosol optical properties. Spectral
      transmission and solar aureole measurements provide an optical source of aerosol
      information, which can be inverted for retrieval of microphysical properties
      (particle size distribution and refractive index). However, to infer these
      aerosol properties from ground-based remote-sensing measurements, special
      numerical inversion methods should be developed and applied. We propose two
      improvements to the existing inversion techniques employed to derive aerosol
      microphysical properties from combined atmospheric transmission and solar aureole
      measurements. First, the aerosol refractive index is directly included in the
      inversion procedure and is retrieved simultaneously with the particle size
      spectra. Second, we allow for real or effective instrumental pointing errors by
      including a correction factor for scattering angle errors as a retrieved
      inversion parameter. The inversion technique is validated by numerical
      simulations and applied to field data. It is shown that ground-based
      sunphotometer measurements enable one to derive the real part of the aerosol
      refractive index with an absolute error of 0.03-0.05 and to distinguish roughly
      between weakly and strongly absorbing aerosols. The aureole angular observation
      scheme can be refined with an absolute accuracy of 0.15-0.19 deg. Offset
      corrections to the scattering angle error are generally found to be small and
      consistently of the order of -0.17. This error magnitude is deduced to be due
      primarily to nonlinear field-of-view averaging effects rather than to
      instrumental errors.

PMID- 18324280
TI  - Active laser cavity particle counters: a fundamental problem and solution for
      airborne application.
AB  - A previously unreported air-density-related detuning effect for active cavity
      aerosol optical particle counters is described, and a simple device for
      correcting the problem is presented. Airborne field tests with and without the
      correction device illustrate the effect and the good degree to which the
      deficiency can be overcome. The effect is shown to have an important impact on
      instrument calibration.

PMID- 18324281
TI  - Aerosol retrievals over the ocean by use of channels 1 and 2 AVHRR data:
      sensitivity analysis and preliminary results.
AB  - We outline the methodology of interpreting channels 1 and 2 Advanced Very High
      Resolution Radiometer (AVHRR) radiance data over the oceans and describe a
      detailed analysis of the sensitivity of monthly averages of retrieved aerosol
      parameters to the assumptions made in different retrieval algorithms. The
      analysis is based on using real AVHRR data and exploiting accurate numerical
      techniques for computing single and multiple scattering and spectral absorption
      of light in the vertically inhomogeneous atmosphere-ocean system. We show that
      two-channel algorithms can be expected to provide significantly more accurate and
      less biased retrievals of the aerosol optical thickness than one-channel
      algorithms and that imperfect cloud screening and calibration uncertainties are
      by far the largest sources of errors in the retrieved aerosol parameters. Both
      underestimating and overestimating aerosol absorption as well as the potentially
      strong variability of the real part of the aerosol refractive index may lead to
      regional and/or seasonal biases in optical-thickness retrievals. The Angstrom
      exponent appears to be the aerosol size characteristic that is least sensitive to
      the choice of aerosol model and should be retrieved along with optical thickness
      as the second aerosol parameter.

PMID- 18324282
TI  - Atmospheric CH4 and H2O monitoring with near-infrared InGaAs laser diodes by the
      SDLA, a balloonborne spectrometer for tropospheric and stratospheric in situ
      measurements.
AB  - The Spectrometre a Diodes Laser Accordables (SDLA), a balloonborne spectrometer
      devoted to the in situ measurement of CH(4) and H(2)O in the atmosphere that uses
      commercial distributed-feedback InGaAs laser diodes in combination with
      differential absorption spectroscopy, is described. Absorption spectra of CH(4)
      (in the 1.653-microm region) and H(2)O (in the 1.393-microm region) are
      simultaneously sampled at 1-s intervals by coupling with optical fibers of two
      near-infrared laser diodes to a Herriott multipass cell open to the atmosphere.
      Spectra of methane and water vapor in an altitude range of approximately 1 to
      approximately 31 km recorded during the recent balloon flights of the SDLA are
      presented. Mixing ratios with a precision error ranging from 5% to 10% are
      retrieved from the atmospheric spectra by a nonlinear least-squares fit to the
      spectral line shape in conjunction with in situ simultaneous pressure and
      temperature measurements.

PMID- 18324284
TI  - Interdigitated electrode-induced phase grating with an electrically switchable
      and tunable period.
AB  - A new design for an adjustable electro-optic phase grating inside a waveguide is
      proposed. The electric field and the refractive-index distribution induced inside
      a waveguide by voltage applied to double-sided periodic interdigitated electrode
      arrays are calculated rigorously on the basis of an original analytical
      technique. The modeling was carried out with the Mathcad software. It is shown
      that the fundamental periodicity of the induced grating inside the waveguide can
      be switched between l and 2l by application of the appropriate voltage, where l
      is the spatial periodicity of the interdigitated electrodes. One can also fine
      tune the peak grating reflectivity by changing the constant component of the
      induced refractive index with the help of the constant component of the electric
      field inside the waveguide. The suggested design can be used as a basic idea for
      a variety of optical communication networking applications, including switching,
      modulation, deflection, and data processing.

PMID- 18324285
TI  - Stable supercontinuum generation in short lengths of conventional dispersion
      shifted fiber.
AB  - By propagating 500-fs pulses through 2.5 m of standard fiber followed by 2 m of
      dispersion-shifted fiber, we generated >200 nm of spectral continuum between 1430
      and 1630 nm, which is flat to less than ?0.5 dB over more than 60 nm. Pulses
      obtained by filtering the continuum show no increase in timing jitter over the
      source laser and are pedestal free to >28 dB, indicating excellent stability and
      coherence. We show that the second- and third-order dispersions of the continuum
      fiber and self-phase modulation are primarily responsible for the continuum
      generation and spectral shaping and found close agreement between simulations and
      experiments.

PMID- 18324286
TI  - Fiber-optic chemical sensing with langmuir-blodgett overlay waveguides.
AB  - Fiber-optic chemical sensing has been demonstrated with a side-polished single
      mode optical fiber, evanescently coupled to chemically sensitive Langmuir
      Blodgett (LB) overlay waveguides. The sensors exhibit a channel-dropping response
      centered on a wavelength that is dependent on the thickness and the refractive
      index of the overlay waveguide. It has been shown that pH-sensitive organic dyes
      proved to be suitable materials for the formation of an overlay waveguide whereas
      LB deposition provides the required thickness control. A theoretical model of the
      sensor response, based on the Kramers-Kronig relations and phase matching of the
      guided modes within the optical fiber and overlay waveguide, shows good agreement
      with experimental results.

PMID- 18324287
TI  - Topograph for inspection of engine cylinder walls.
AB  - The microstructural inspection of engine cylinder walls is an important task for
      quality management in the automotive industry. Until recently, mainly tactile
      methods were used for this purpose. We present an optical instrument based on
      microscopic fringe projection that permits fast, reliable, and nondestructive
      measurements of microstructure. The field of view is 0.8 mm x 1.2 mm, with a
      spatial sampling of 1100 x 700 pixels. In contrast to conventional tactile
      sensors, the optical method provides fast in situ three-dimensional surface
      characterizations that provide more information about the surface than do line
      profiles. Measurements are presented, and advantages of this instrument for
      characterization of a surface are discussed.

PMID- 18324288
TI  - Efficient pumping scheme for neodymium-doped materials by direct excitation of
      the upper lasing level.
AB  - An efficient pumping scheme that involves direct excitation of the upper lasing
      level of the Nd(3+) ion is demonstrated experimentally. The results obtained for
      direct upper laser level pumping of Nd:YAG R2 (869 nm) and Nd:YVO(4) (880 nm)
      were compared with traditional approximately 808-nm pump band excitation. A
      tunable cw Ti:sapphire laser was used as the pump source. In Nd:YAG, the
      oscillator slope efficiency increased by 10% and the threshold decreased by 11%.
      In Nd:YVO(4), the slope efficiency increased by 5% and the threshold decreased by
      11%. These results agree with theory. The increase in optical efficiency
      indicates that laser material thermal loading can be substantially reduced.

PMID- 18324289
TI  - Femtosecond-pulse cavity-dumped solid-state oscillator design and application to
      ultrafast microscopy.
AB  - The construction, modeling, and performance characteristics of a new resonator
      design for ultrafast cavity-dumped oscillators are presented. An acousto-optic
      Bragg cell was incorporated at the end of the longer arm of a Ti:sapphire
      oscillator rather than in the shorter arm as in several recent studies. The new
      arrangement improves the pulse intensity stability of the oscillator and
      significantly reduces the effort required in construction. The experimental
      findings are supported by comparison of the stability regions of the laser
      cavities based on the two different designs. To demonstrate the potential of
      cavity-dumped oscillators for spatially resolved ultrafast spectroscopy studies,
      the pulse duration is characterized at the focal plane of two achromatic high
      N.A. oil-immersion objectives with different amounts of flat-field correction.
      Transform-limited pulse widths as short as 15 fs are obtained. To our knowledge,
      this is the shortest pulse duration measured with true high-N.A. (N.A. > 1)
      focusing conditions.

PMID- 18324290
TI  - Third-harmonic generation microscopy by use of a compact, femtosecond fiber laser
      source.
AB  - We demonstrate the first use, to our knowledge, of a compact, diode-pumped,
      femtosecond fiber laser for third-harmonic generation (THG) microscopy. We
      discuss the utility of this technique, as well as the technical issues involved
      in using this compact source, and demonstrate the first use, to our knowledge, of
      imaging by THG backlighting.

PMID- 18324291
TI  - Single-mode, singly resonant, pulsed periodically poled lithium niobate optical
      parametric oscillator.
AB  - We report single longitudinal mode operation of a pulsed Nd:YAG pumped
      periodically poled lithium niobate optical parametric oscillator (OPO). The
      combination of a prism and an etalon provides both coarse and fine spectral
      resolution, thereby eliminating parasitic resonant oscillation of cascaded signal
      wavelengths, idler wavelengths, and adjacent longitudinal modes of the signal
      field. Optical bandwidths of less than 300 MHz have been obtained at signal
      wavelengths between 1.47 and 1.59 mum. In comparison with broadband operation,
      the single-mode OPO shows only a 9% reduction in pump depletion with a negligible
      reduction in extraction efficiency.

PMID- 18324292
TI  - Noncollinear-pumped KTP optical parametric oscillator.
AB  - A theoretical analysis and an experimental study are presented on the phase
      matching condition of noncollinearly pumped optical parametric oscillators
      (OPO's) based on a noncritical phase-matching potassium titanyl phosphate (KTP)
      OPO. It is shown that noncollinearly pumped, double-pass, singly resonant optical
      parametric oscillators maintain the advantage of round-trip parametric gain in a
      collinear pump, since in this case the two generated signal waves are coherent,
      which results in high conversion efficiency and low pump threshold. With this KTP
      OPO we achieved 31% energy conversion efficiency from a 1064-nm pump wave to 1572
      nm eye-safe output. In addition, because the incident pump beam is not
      perpendicular to the OPO cavity mirrors and consequently no reflected beam flows
      back into the pump source, we can avoid employing optical isolators.

PMID- 18324293
TI  - Extended sphere method for complete investigation of the phase-matching
      properties of sum- and difference-frequency generation.
AB  - We demonstrate the feasibility of a complete experimental investigation of the
      phase-matching properties of sum- and difference-frequency generation in a single
      crystal cut as a sphere over its entire transparency range. The class of the
      studied crystal is the only initial data that is required. This feasibility study
      was carried out with rubidium titanyl arsenate.

PMID- 18324294
TI  - Demonstration of an optical isolator by use of a nonreciprocal phase shift.
AB  - The experimental study of an optical isolator by use of a nonreciprocal phase
      shift is demonstrated. The isolator has an optical interferometer composed of
      tapered couplers, nonreciprocal phase shifters, and a reciprocal phase shifter.
      The isolator, designed for a 1.55-microm wavelength, was fabricated to
      investigate the characteristics of each component. The branching and coupling
      characteristics of the tapered coupler were measured. The nonreciprocal and
      reciprocal phase shifts were also evaluated. By applying an external magnetic
      field to the interferometer, we confirmed the nonreciprocal phase shift in the
      interferometric isolator.

PMID- 18324295
TI  - Analytical solution of the two-frequency lidar inversion technique.
AB  - A two-frequency lidar inversion on the assumptions of a range-independent
      relationship between the extinction coefficients of the two considered lidar
      wavelengths and of constant extinction-to-backscatter ratios was originally
      developed by Potter [Appl. Opt. 26, 1250 (1987)]. It is an iterative procedure to
      retrieve the boundary value for solution of the single-scatter lidar equation.
      This boundary value is expressed by the aerosol transmission along the evaluated
      lidar path. Recently, Kunz [Appl. Opt. 38, 1015 (1999)] stated that there is not
      enough information in the lidar signals of two wavelengths to obtain a unique
      solution for the boundary value and hence for the aerosol extinction profile. It
      is shown that a unique solution of the two-frequency lidar inversion exists, for
      which an analytical expression of the boundary value and, hence, the aerosol
      extinction profile, is given.

PMID- 18324296
TI  - Monte Carlo approach for solving the radiative transfer equation over mountainous
      and heterogeneous areas.
AB  - An algorithm based on the Monte Carlo method is developed to solve the radiative
      transfer equation in the reflective domain (0.4-4 microm) of the solar spectrum
      over rugged terrain. This algorithm takes into account relief, spatial
      heterogeneity, and ground bidirectional reflectance. The method permits the
      computation of irradiance components at ground level and radiance terms reaching
      an airborne or satelliteborne sensor. The Monte Carlo method consists of
      statistically simulating the paths of photons inside the Earth-atmosphere system
      to reproduce physical phenomena while introducing neither analytical modeling nor
      assumption. The potentialities of the code are then depicted over different types
      of landscape, including a seashore, a desert region, and a steep mountainous
      valley.

PMID- 18324297
TI  - Satellite retrieval of the absorption coefficient of phytoplankton phycoerythrin
      pigment: theory and feasibility status.
AB  - Oceanic radiance model inversion methods are used to develop a comprehensive
      algorithm for retrieval of the absorption coefficients of phycourobilin (PUB)
      pigment, type I phycoerythrobilin (PEB) pigment rich in PUB, and type II PEB
      deficient in PUB pigment (together with the usual "big three" inherent optical
      properties: the total backscattering coefficient and the absorption coefficients
      of chromophoric dissolved organic matter (CDOM)-detritus and phytoplankton). This
      fully modeled inversion algorithm is then simplified to yield a hybrid modeled
      unmodeled inversion algorithm in which the phycoerythrin (PE) absorption
      coefficient is retrieved as unmodeled 488-nm absorption (which exceeds the
      modeled phytoplankton and the CDOM-detritus absorption coefficients). Each
      algorithm was applied to water-leaving radiances, but only hybrid modeled
      unmodeled inversions yielded viable retrievals of the PE absorption coefficient.
      Validation of the PE absorption coefficient retrieval was achieved by relative
      comparison with airborne laser-induced PEB fluorescence. The modeled-unmodeled
      retrieval of four inherent optical properties by direct matrix inversion is rapid
      and well conditioned, but the accuracy is strongly limited by the accuracy of the
      three principal inherent optical property models across all four spectral bands.
      Several research areas are identified to enhance the radiance-model-based
      retrievals: (a) improved PEB and PUB absorption coefficient models, (b) PE
      spectral shifts induced by PUB chromophore substitution at chromophore binding
      sites, (c) specific absorption-sensitive phytoplankton absorption modeling, (d)
      total constituent backscattering modeling, (e) unmodeled carotinoid and
      phycocyanin absorption that are not now accounted for in the chlorophyll
      dominated phytoplankton absorption coefficient model, and (f) iterative inversion
      techniques to solve for six constituents with only five radiances. Although
      considerable progress has been made toward the satellite recovery of PE
      absorption, the maturity of the retrieval is presently insufficient for routine
      global application. Instead it must currently be used on a regional basis where
      localized ship and aircraft validation can be made available. The algorithm was
      developed for the MODIS (Moderate-Resolution Imaging Spectroradiometer) sensor
      but is applicable to any sensor having comparable band locations.

PMID- 18324298
TI  - Estimation of the remote-sensing reflectance from above-surface measurements.
AB  - The remote-sensing reflectance R(rs) is not directly measurable, and various
      methodologies have been employed in its estimation. I review the radiative
      transfer foundations of several commonly used methods for estimating R(rs), and
      errors associated with estimating R(rs) by removal of surface-reflected sky
      radiance are evaluated using the Hydrolight radiative transfer numerical model.
      The dependence of the sea surface reflectance factor rho, which is not an
      inherent optical property of the surface, on sky conditions, wind speed, solar
      zenith angle, and viewing geometry is examined. If rho is not estimated
      accurately, significant errors can occur in the estimated R(rs) for near-zenith
      Sun positions and for high wind speeds, both of which can give considerable Sun
      glitter effects. The numerical simulations suggest that a viewing direction of 40
      deg from the nadir and 135 deg from the Sun is a reasonable compromise among
      conflicting requirements. For this viewing direction, a value of rho
      approximately 0.028 is acceptable only for wind speeds less than 5 m s(-1). For
      higher wind speeds, curves are presented for the determination of rho as a
      function of solar zenith angle and wind speed. If the sky is overcast, a value of
      rho approximately 0.028 is used at all wind speeds.

PMID- 18324299
TI  - Coherent Doppler lidar signal spectrum with wind turbulence.
AB  - The average signal spectrum (periodogram) for coherent Doppler lidar is
      calculated for a turbulent wind field. Simple approximations are compared with
      the exact calculation. The effects of random errors in the zero velocity
      reference, the effects of averaging spectral estimates by use of multiple lidar
      pulses, and the effects of the range dependence of the lidar signal power over
      the range gate are included. For high spatial resolution measurements the lidar
      signal power is concentrated around one spectral estimate (spectral bin), and
      correct interpretation of the contribution from turbulence is difficult because
      of the effects of spectral leakage. For range gates that are larger than the
      lidar pulse volume, the signal power is contained in many spectral bins and the
      effects of turbulence can be determined accurately for constant signal power over
      the range gate and for the far-field range dependence of the signal power.

PMID- 18324301
TI  - Laser-raster spectrometer for time-resolved recording of transient absorption.
AB  - For measurements of transient absorption a laser-raster technique has been found
      to be surprisingly sensitive. It utilizes spatial separation of excitation and
      probing by employing a fast-flowing jet stream. The time resolution is determined
      by the flow velocity and the focal diameters of the continuous excitation and
      probing laser beams. Changes in transmission can be detected in the spectral
      region from 350 to 1000 nm. A dual-frequency modulation technique is used to
      achieve a sensitivity of 10(-4). The time resolution is 0.5 mus. The performance
      of this spectrometer is demonstrated by measurement of the absorption of the
      transient states of Rhodamine 6G dye in ethylene glycol.

PMID- 18324302
TI  - Effect of beam-splitter emission in Fourier-transform emission spectroscopy.
AB  - A simple model of an emission Fourier-transform spectrometer is provided for a
      beam splitter with infinitesimal thickness but with general optical properties
      otherwise. Using the principle of conservation of energy, we derived the rigorous
      expressions that relate the interferograms from three different signals (source,
      reference, and beam-splitter emission), which are simultaneously observed by the
      detector. The relationship among phase and amplitude of the three interferograms
      is evaluated. The results indicate that the behavior of a Fourier-transform
      emission spectrometer may be more complicated than what is assumed in some
      models. Calibration procedures should reflect the implications of this rigorous
      approach.

PMID- 18324303
TI  - Resonance ionization spectroscopy in a thermal lithium beam by means of diode
      lasers.
AB  - We measured two-step photoion current spectra by using a semiconductor laser and
      a Q-switched Nd:YAG laser with fourth-harmonic generation in an atomic lithium
      beam. The number of ions measured was compared with an estimate from the diode
      laser absorption measurement that uses a set of precisely solved rate equations.
      We explain the saturation effects on absorption by using transit time relaxation
      and detailed calculations of the ionization levels.

PMID- 18324304
TI  - Evaluation of an ultrabroadband high-gain amplification technique for chirped
      pulse amplification facilities.
AB  - Recently, an amplification technique for ultrashort pulses was explored in detail
      in a theoretical paper by Ross et al. [Opt. Commun. 144, 125 (1997)]. The
      technique, based on nonlinear optics, is called optical parametric chirped pulse
      amplification. It has a number of features that, in principle, make it highly
      attractive. It primarily offers extremely large gains simultaneously with
      extremely large bandwidths. Additional attractions are virtually no spatial and
      temporal phase distortion of the amplified pulse, high efficiencies and a low
      thermal loading, reduced amplified spontaneous emission levels, small optical
      material lengths, and an inherent simplicity of implementation. We present an
      evaluation of the technique as a front end amplifier for the ultrashort pulse
      amplification chain of the Vulcan laser system. Such a device could replace some
      of the existing amplification in Nd:glass and additionally have a wider effect as
      a direct replacement of Ti:sapphire regenerative amplifiers on large-scale
      chirped pulse amplification scale facilities.

PMID- 18324305
TI  - Single-reflection regime of X rays that travel into a monocapillary.
AB  - We present an analysis of the transmission of x rays through a single
      monocapillary under the single-reflection regime. Because ray tracing does not
      provide an explanation for experimental data, we give a qualitative
      interpretation of the observed behavior within the framework of wave theory.

PMID- 18324309
TI  - Memory in microbes: quantifying history-dependent behavior in a bacterium.
AB  - Memory is usually associated with higher organisms rather than bacteria. However,
      evidence is mounting that many regulatory networks within bacteria are capable of
      complex dynamics and multi-stable behaviors that have been linked to memory in
      other systems. Moreover, it is recognized that bacteria that have experienced
      different environmental histories may respond differently to current conditions.
      These "memory" effects may be more than incidental to the regulatory mechanisms
      controlling acclimation or to the status of the metabolic stores. Rather, they
      may be regulated by the cell and confer fitness to the organism in the
      evolutionary game it participates in. Here, we propose that history-dependent
      behavior is a potentially important manifestation of memory, worth classifying
      and quantifying. To this end, we develop an information-theory based conceptual
      framework for measuring both the persistence of memory in microbes and the amount
      of information about the past encoded in history-dependent dynamics. This method
      produces a phenomenological measure of cellular memory without regard to the
      specific cellular mechanisms encoding it. We then apply this framework to a
      strain of Bacillus subtilis engineered to report on commitment to sporulation and
      degradative enzyme (AprE) synthesis and estimate the capacity of these systems
      and growth dynamics to 'remember' 10 distinct cell histories prior to application
      of a common stressor. The analysis suggests that B. subtilis remembers, both in
      short and long term, aspects of its cell history, and that this memory is
      distributed differently among the observables. While this study does not examine
      the mechanistic bases for memory, it presents a framework for quantifying memory
      in cellular behaviors and is thus a starting point for studying new questions
      about cellular regulation and evolutionary strategy.

PMID- 18324310
TI  - Negative feedback regulation of T cells via interleukin-2 and FOXP3 reciprocity.
AB  - As interleukin-2 (IL2) is central to the clonal expansion of antigen-selected T
      cells, we investigated the relationship between IL2 and the negative regulatory
      transcription factor FOXP3. We found IL2 to be responsible for T cell antigen
      receptor (TCR)-activated FOXP3 expression by both CD4+ and CD8+ human T cells,
      and as anticipated, FOXP3 expression restricted TCR-stimulated IL2 expression.
      However, no evidence could be found that FOXP3+ cells actively suppress IL2
      expression by FOXP3- cells. These data are consistent with an IL2/FOXP3-dependent
      negative feedback loop that normally regulates the T cell immune response. It
      follows that a defect in this negative feedback loop as a result of a deficiency
      of either IL2 or FOXP3 will lead to a hyperproliferative autoimmune syndrome,
      without the necessity of invoking an active suppressive function for FOXP3+ T
      cells.

PMID- 18324313
TI  - Time to heal?

PMID- 18324314
TI  - Physician performance measurement: potential benefits outweigh the challenges.

PMID- 18324315
TI  - Pharmacologic treatment of ADHD: road conditions in driving patients to
      successful outcomes.
AB  - The names assigned to attention-deficit/hyperactive disorder (ADHD) have changed
      over the years. ADHD cannot be cured, and the patient with ADHD journeys through
      life with a burden. Although ADHD is most commonly studied in school-aged
      children, it is a syndrome that spans the life cycle, through adolescence and
      into adulthood. Improvements in patient adherence to pharmacologic treatment,
      attributable to the launch of new formulations, the availability of new non
      schedule II drugs, and the development of novel drugs in late-stage clinical
      trials, are transforming the treatment of ADHD. For example, atomoxetine is a
      nonstimulant treatment, and lisdexamfetamine was developed with the goal of
      providing an extended duration of effect with a reduced potential for abuse,
      overdose toxicity, and drug tampering. Known adverse effects of stimulant
      treatment of ADHD include appetite suppression and sleep disturbance. Other
      adverse effects, such as growth suppression and substance use disorder, are
      controversial. The US Food and Drug Administration (FDA) recently issued a public
      health advisory for drugs approved for the treatment of ADHD to provide more
      information for patients about potential risks of ADHD medications. Additional
      research is needed on approaches for treating ADHD in adolescents transitioning
      into adulthood, as are studies on the relationships between ADHD and
      comorbidities such as substance use disorder.

PMID- 18324316
TI  - Combined inferior vena cava & renal vein thromboses: case and synopsis of
      thromboembolism in inflammatory bowel disease.
AB  - Thromboembolic phenomena have long been known to be an extraintestinal
      manifestation of inflammatory bowel disease, with the deep veins of the legs and
      the pulmonary vasculature being the most commonly affected sites. Research has
      identified factors associated with inflammatory bowel disease that contribute to
      prothrombotic risk, but understanding of the pathophysiology is incomplete.
      Symptoms of thromboembolism can be vague, may be overlooked, or may be attributed
      to the consequences of protracted inflammatory bowel disease and/or side effects
      of its medications. We present a rare case of combined inferior vena cava and
      bilateral renal vein thromboses as well as pulmonary embolism in a young woman
      with ulcerative pancolitis in partial remission. Our patient presented with
      nonspecific symptoms that would not immediately raise clinical suspicion of
      severe thromboembolism, and thus we provide our recommendations for diagnosis and
      treatment.

PMID- 18324317
TI  - Trying to resolve a dispute over the best way to diagnose cervical neoplasia in a
      developing country.

PMID- 18324318
TI  - Mother was right about cod liver oil.

PMID- 18324319
TI  - A reader and author respond to "Connecting America's communities requires social
      capital and changes in how we pay for healthcare".

PMID- 18324320
TI  - Ending the tobacco problem.

PMID- 18324321
TI  - A man with an umbilical ulcer.

PMID- 18324322
TI  - Failed angiographic embolization in uterine arteriovenous malformation: a case
      report and review of the literature.

PMID- 18324323
TI  - Readers respond to "Integrative medicine: sorting fact from fiction".

PMID- 18324324
TI  - Reimbursement for new technologies: the GERD maze is not patient-friendly.

PMID- 18324325
TI  - Spontaneous perforation of pyometra presented as an acute abdomen: a case report.
AB  - Spontaneous perforation of pyometra is a rare pathologic condition that presents
      as diffuse peritonitis. This report describes an interesting case of spontaneous
      uterine perforation that mimicked gut perforation clinically and was finally
      diagnosed at exploratory laparotomy. Although rare, perforation of pyometra
      should be kept as one of the differential diagnosis in an elderly woman with an
      acute abdomen. A high index of suspicion is required to make a correct
      preoperative diagnosis, which allows early intervention, thus reducing morbidity
      and mortality.

PMID- 18324326
TI  - Gastroparesis--current concepts and considerations.

PMID- 18324327
TI  - Autoimmune inflammatory myopathy in pregnancy.
AB  - Autoimmune diseases such as systemic sclerosis, Wegner's granulomatosis, and
      polyarteritis nodosa are rarely seen in pregnancy, unlike systemic lupus
      erythematosus, whose association with pregnancy is well studied. Dermatomyositis
      is a protean disease that affects women in reproductive age. There are only a few
      case reports documenting the outcome of pregnancy in patients with
      dermatomyositis/polymyositis. The disease is usually considered to have an
      adverse effect on pregnancy. Fetal prognosis is guided by the severity of
      maternal disease and is usually good when the disease remains inactive during
      pregnancy.

PMID- 18324328
TI  - A reader and author respond to "Reforms for rating media: disclosure, not
      censorship".

PMID- 18324329
TI  - ePatients: engaging patients in their own care.

PMID- 18324330
TI  - Esoteric or exoteric? Music in medicine.

PMID- 18324331
TI  - Why is evidence-based medicine the legal standard of practice?

PMID- 18324332
TI  - A case report of cor pulmonale in a woman without exposure to tobacco smoke: an
      example of the risks of indoor wood burning.
AB  - We present the case of a 67-year-old woman with chronic cor pulmonale. She never
      smoked tobacco and had no other risk factors for pulmonary disease. In developed
      nations, chronic obstructive lung disease and cor pulmonale are overwhelmingly
      associated with tobacco use. However, indoor air pollution, most commonly due to
      burning of solid biomass fuel such as wood, can cause similar clinical syndromes.
      At our teaching hospital, there is an epidemic of chronic cor pulmonale among
      nonsmoking women. We attribute this sex predilection to women's greater exposure
      to wood smoke. Physicians must be cognizant of its risks and counsel patients on
      prevention strategies such as improved ventilation.

PMID- 18324333
TI  - The use of amielle vaginal trainers as adjuvant in the treatment of
      vestibulodynia: an observational multicentric study.
AB  - OBJECTIVE: To assess the effectiveness of a specific set of vaginal dilators
      (Amielle Comfort) as a part of vestibulodynia therapy. STUDY DESIGN: Fifteen
      women referred for vestibulodynia, localized vulvodynia, were advised to use
      vaginal dilators (Amielle Comfort) accompanied by standardized instructions,
      after previously receiving 1 or more therapies for the vestibulodynia. RESULTS:
      The post-treatment Marinoff scale for dyspareunia significantly improved in
      patients after vaginal dilator treatment compared with baseline values (2.2 +/-
      0.4 vs 1.1 +/- 0.9; P < .01), and the Female Sexual Function Index scores were
      significantly improved compared with the prestudy values (16.3 +/- 5.5 vs 25.3 +/
      7.5; P < .01). CONCLUSION: Among women with previous therapy for vestibulodynia,
      vaginal dilator use was associated with improvement in symptoms. Vaginal dilators
      can play an important role in overcoming pelvic floor muscular responses that
      remain and sometimes increase after pain perception has decreased.

PMID- 18324334
TI  - Substance abuse in patients with attention-deficit/hyperactivity disorder.
AB  - Substance use disorder (SUD) is a common comorbidity of attention
      deficit/hyperactivity disorder (ADHD) that is frequently seen during adolescence.
      Physicians who treat patients with ADHD need to be aware of both the behavioral
      and medical signs of substance abuse and closely screen their patients for SUD.
      Optimal treatment of the symptoms of ADHD is the most effective way to reduce the
      incidence of SUD, but the use of stimulants, the first-line therapy for ADHD, is
      associated with an appreciable degree of abuse and misuse of therapeutic drugs.
      Cardiovascular and psychiatric risks with ADHD drugs have resulted in recent
      labeling changes for these drugs. A correct diagnosis of ADHD is important in
      validating the use of stimulant medication. New strategies for effectively
      treating ADHD that may minimize the risk for drug abuse are being developed and
      include extended-release formulations of currently used drugs, new nonstimulant
      drugs for the treatment of ADHD, and novel prodrugs that optimize therapeutic
      plasma concentrations of drugs. Nonmedication or psychosocial treatments,
      especially for adult ADHD, are also available. Further assessment of these
      strategies should permit the development of new approaches to the treatment of
      ADHD that reduce the risk for abuse and misuse of stimulant medications.

PMID- 18324335
TI  - The efficacy of DNA vaccination is enhanced in mice by targeting the encoded
      protein to dendritic cells.
AB  - DNA vaccines promote an immune response by providing antigen-encoding DNA to the
      recipient, but the efficacy of such vaccines needs improving. Many approaches
      have considerable potential but currently induce relatively weak immune responses
      despite multiple high doses of DNA vaccine. Here, we asked whether targeting
      vaccine antigens to DCs would increase the immunity and protection that result
      from DNA vaccines. To determine this, we generated a DNA vaccine encoding a
      fusion protein comprised of the vaccine antigen and a single-chain Fv antibody
      (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Following
      vaccination of mice, the vaccine antigen was expressed selectively by DCs, which
      were required for the increased efficacy of MHC class I and MHC class II antigen
      presentation relative to a control scFv DNA vaccine. In addition, a DNA vaccine
      encoding an HIV gag p41-scFv DEC205 fusion protein induced 10-fold higher
      antibody levels and increased numbers of IFN-gamma-producing CD4+ and CD8+ T
      cells. After a single i.m. injection of the DNA vaccine encoding an HIV gag p41
      scFv DEC205 fusion protein, mice were protected from an airway challenge with a
      recombinant vaccinia virus expressing the HIV gag p41, even with 1% of the dose
      of nontargeted DNA vaccine. The efficacy of DNA vaccines therefore may be
      enhanced by inclusion of sequences such as single-chain antibodies to target the
      antigen to DCs.

PMID- 18324336
TI  - Mitotic spindle destabilization and genomic instability in Shwachman-Diamond
      syndrome.
AB  - Deficiencies in the SBDS gene result in Shwachman-Diamond syndrome (SDS), an
      inherited bone marrow failure syndrome associated with leukemia predisposition.
      SBDS encodes a highly conserved protein previously implicated in ribosome
      biogenesis. Using human primary bone marrow stromal cells (BMSCs), lymphoblasts,
      and skin fibroblasts, we show that SBDS stabilized the mitotic spindle to prevent
      genomic instability. SBDS colocalized with the mitotic spindle in control primary
      BMSCs, lymphoblasts, and skin fibroblasts and bound to purified microtubules.
      Recombinant SBDS protein stabilized microtubules in vitro. We observed that
      primary BMSCs and lymphoblasts from SDS patients exhibited an increased incidence
      of abnormal mitoses. Similarly, depletion of SBDS by siRNA in human skin
      fibroblasts resulted in increased mitotic abnormalities and aneuploidy that
      accumulated over time. Treatment of primary BMSCs and lymphoblasts from SDS
      patients with nocodazole, a microtubule destabilizing agent, led to increased
      mitotic arrest and apoptosis, consistent with spindle destabilization.
      Conversely, SDS patient cells were resistant to taxol, a microtubule stabilizing
      agent. These findings suggest that spindle instability in SDS contributes to bone
      marrow failure and leukemogenesis.

PMID- 18324337
TI  - Production of CFTR-null and CFTR-DeltaF508 heterozygous pigs by adeno-associated
      virus-mediated gene targeting and somatic cell nuclear transfer.
AB  - Progress toward understanding the pathogenesis of cystic fibrosis (CF) and
      developing effective therapies has been hampered by lack of a relevant animal
      model. CF mice fail to develop the lung and pancreatic disease that cause most of
      the morbidity and mortality in patients with CF. Pigs may be better animals than
      mice in which to model human genetic diseases because their anatomy,
      biochemistry, physiology, size, and genetics are more similar to those of humans.
      However, to date, gene-targeted mammalian models of human genetic disease have
      not been reported for any species other than mice. Here we describe the first
      steps toward the generation of a pig model of CF. We used recombinant adeno
      associated virus (rAAV) vectors to deliver genetic constructs targeting the CF
      transmembrane conductance receptor (CFTR) gene to pig fetal fibroblasts. We
      generated cells with the CFTR gene either disrupted or containing the most common
      CF-associated mutation (DeltaF508). These cells were used as nuclear donors for
      somatic cell nuclear transfer to porcine oocytes. We thereby generated
      heterozygote male piglets with each mutation. These pigs should be of value in
      producing new models of CF. In addition, because gene-modified mice often fail to
      replicate human diseases, this approach could be used to generate models of other
      human genetic diseases in species other than mice.

PMID- 18324338
TI  - Adeno-associated virus-targeted disruption of the CFTR gene in cloned ferrets.
AB  - Somatic cell gene targeting combined with nuclear transfer cloning presents
      tremendous potential for the creation of new, large-animal models of human
      diseases. Mouse disease models often fail to reproduce human phenotypes,
      underscoring the need for the generation and study of alternative disease models.
      Mice deficient for CFTR have been poor models for cystic fibrosis (CF), lacking
      many aspects of human CF lung disease. In this study, we describe the production
      of a CFTR gene-deficient model in the domestic ferret using recombinant adeno
      associated virus-mediated gene targeting in fibroblasts, followed by nuclear
      transfer cloning. As part of this approach, we developed a somatic cell
      rejuvenation protocol using serial nuclear transfer to produce live CFTR
      deficient clones from senescent gene-targeted fibroblasts. We transferred 472
      reconstructed embryos into 11 recipient jills and obtained 8 healthy male ferret
      clones heterozygous for a disruption in exon 10 of the CFTR gene. To our
      knowledge, this study represents the first description of genetically engineered
      ferrets and describes an approach that may be of substantial utility in modeling
      not only CF, but also other genetic diseases.

PMID- 18324339
TI  - High light induced accumulation of two isoforms of the CF1 alpha-subunit in
      mesophyll and bundle sheath chloroplasts of C4 plants.
AB  - The effect of light irradiance on the amount of ATP synthase alpha-subunit in
      mesophyll (M) and bundle sheath (BS) chloroplasts of C(4) species such as maize
      (Zea mays L., type NADP-ME), millet (Panicum miliaceum, type NAD-ME) and guinea
      grass (Panicum maximum, type PEP-CK) was investigated in plants grown under high,
      moderate and low light intensities equal to 800, 350 and 50 micromol photons m(
      2) s(-1), respectively. The results demonstrate that alpha-subunit of ATP
      synthase in both M and BS chloroplasts is altered by light intensity, but
      differently in the investigated species. Moreover, we identified two isoforms of
      the CF(1) alpha-subunit, called alpha and alpha. The CF(1) alpha-subunit was the
      major isoform and was present in all light conditions, whereas alpha was the
      minor isoform in low light. A strong increase in the level of the alpha-subunit
      in maize mesophyll and bundle sheath thylakoids was observed after 50 h of high
      light treatment. The alpha and alpha-subunits from investigated C(4) species
      displayed apparent molecular masses of 64 and 67 kDa, respectively, on SDS/PAGE.
      The presence of the alpha-subunit of ATPase was confirmed in isolated CF(1)
      complex, where it was recognized by antisera to the alpha-subunit. The N-terminal
      sequence of alpha-subunit is nearly identical to that of alpha. Our results
      indicate that both isoforms coexist in M and BS chloroplasts during plant growth
      at all irradiances. We suggest the existence in M and BS chloroplasts of C(4)
      plants of a mechanism(s) regulating the ATPase composition in response to light
      irradiance. Accumulation of the alpha isoform may have a protective role under
      high light stress against over protonation of the thylakoid lumen and
      photooxidative damage of PSII.

PMID- 18324340
TI  - Tenocyclidine treatment in soman-poisoned rats--intriguing results on
      genotoxicity versus protection.
AB  - This study aimed to evaluate the antidotal potency of tenocyclidine (TCP) that
      probably might protect acetylcholinesterase (AChE) in the case of organophosphate
      poisoning. TCP was tested alone as a pretreatment or in combination with atropine
      as a therapy in rats poisoned with (1/4) and (1/2) of LD(50) of soman. Possible
      genotoxic effects of TCP in white blood cells and brain tissue were also studied.
      Results were compared with previous findings on the adamantyl tenocyclidine
      derivative TAMORF. TCP given alone as pretreatment, 5 min before soman, seems to
      be superior in the protection of cholinesterase (ChE) catalytic activity in the
      plasma than in brain, especially after administration of the lower dose of soman.
      Plasma activities of the enzyme after a joint treatment with TCP and soman were
      significantly increased at 30 min (P<0.001) and 24 h (P=0.0043), as compared to
      soman alone. TCP and atropine, given as therapy, were more effective than TCP
      administered alone as a pretreatment. The above therapy significantly increased
      activities of the enzyme at 30 min (P=0.046) and 24 h (P<0.001), as compared to
      controls treated with (1/4) LD(50) of soman alone. Using the alkaline comet
      assay, acceptable genotoxicity of TCP was observed. However, the controversial
      role of TCP in brain protection of soman-poisoned rats should be studied further.

PMID- 18324341
TI  - Amino acid substitutions of His296 alter the catalytic properties of Zymomonas
      mobilis 10232 levansucrase.
AB  - His296 of Zymomonas mobilis levansucrase (EC 2.4.1.10) is crucial for the
      catalysis of the transfructosylation reaction. The three-dimensional structures
      of levansucrases revealed the His296 is involved in the substrate recognition and
      binding. In this study, nine mutants were created by site-directed mutagenesis,
      in which His296 was substituted with amino acids of different polarity, charge
      and length. The substitutions of His296 with Arg or Trp retained partial
      hydrolysis and transfructosylation activities. The positively charged Lys
      substitution resulted in a 2.5-fold increase of sucrose hydrolysis. Substitutions
      with short (Cys or Ser), negatively charged (Glu) or polar (Tyr) amino acids
      virtually abolished both the activities. Analysis of transfructosylation products
      indicated that the mutants synthesized different oligosaccharides, suggesting
      that amino acid substitutions of His296 strongly affected both the enzyme
      activity and transfructosylation products.

PMID- 18324342
TI  - Development of prognostic nomograms for individualizing 5-year and 10-year
      fracture risks.
AB  - We have developed clinical nomograms for predicting 5-year and 10-year fracture
      risks for any elderly man or woman. The nomograms used age and information
      concerning fracture history, fall history, and BMD T-score or body weight.
      INTRODUCTION: Although many fracture risk factors have been identified, the
      translation of these risk factors into a prognostic model that can be used in
      primary care setting has not been well realized. The present study sought to
      develop a nomogram that incorporates non-invasive risk factors to predict 5-year
      and 10-year absolute fracture risks for an individual man and woman. METHODS: The
      Dubbo Osteoporosis Epidemiology Study was designed as a community-based
      prospective study, with 1358 women and 858 men aged 60+ years as at 1989.
      Baseline measurements included femoral neck bone mineral density (FNBMD), prior
      fracture, a history of falls and body weight. Between 1989 and 2004, 426 women
      and 149 men had sustained a low-trauma fracture (not including morphometric
      vertebral fractures). Two prognostic models based on the Cox's proportional
      hazards analysis were considered: model I included age, BMD, prior fracture and
      falls; and model II included age, weight, prior fracture and fall. RESULTS:
      Analysis of the area under the receiver operating characteristic curve (AUC)
      suggested that model I (AUC = 0.75 for both sexes) performed better than model II
      (AUC = 0.72 for women and 0.74 for men). Using the models' estimates, we
      constructed various nomograms for individualizing the risk of fracture for men
      and women. If the 5-year risk of 10% or greater is considered "high risk", then
      virtually all 80-year-old men with BMD T-scores < -1.0 or 80-year-old women with
      T-scores < -2.0 were predicted to be in the high risk group. A 60-year-old
      woman's risk was considered high risk only if her BMD T-scores < or = -2.5 and
      with a prior fracture; however, no 60-year-old men would be in the high risk
      regardless of their BMD and risk profile. CONCLUSION: These data suggest that the
      assessment of fracture risk for an individual cannot be based on BMD alone, since
      there are clearly various combinations of factors that could substantially
      elevate an individual's risk of fracture. The nomograms presented here can be
      useful for individualizing the short- and intermediate-term risk of fracture and
      identifying high-risk individuals for intervention to reduce the burden of
      fracture in the general population.

PMID- 18324343
TI  - Consolidation in an individual transferable quota regime: lessons from New
      Zealand, 1986-1999.
AB  - Market-based approaches to environmental regulation (such as tradable permits or
      transferable quotas) are frequently offered as innovative solutions to many
      environmental problems. Globally, one of the most well-established forms of this
      approach is individual transferable quotas (or ITQs) in fisheries management.
      Within the natural resource management community, there is considerable debate
      over the effects ITQs have on the fishing industry and fisher behavior although
      this approach is not well-established in the United States. The previously
      imposed moratorium on ITQs in the United States has expired and the 2006
      reauthorization of the Magnuson-Stevens Act explicitly provides for limited
      access privileges (LAPs). A variety of fishers, regulators, and conservation
      organizations are enthusiastically seeking to introduce ITQ management. With
      debate over whether and how ITQs should be used in American fisheries
      reinvigorated, it is timely to examine the evidence on the social and economic
      effects of ITQs in other nations' fisheries. After briefly summarizing the debate
      on ITQs, we examine the case of New Zealand, one of the earliest and longest
      lived ITQ-based fisheries regimes. We use multiple data sources and methods to
      analyze the extent to which industry consolidation and aggregation has occurred,
      including surveys of industry participants, expert interviews, reviews of
      academic reports and analyses, analysis of trade publications, and direct
      analysis of quota ownership patterns. This analysis shows a more complex outcome
      than recent debates in the ITQ literature would predict. These findings suggest
      that policy makers considering ITQs can learn from the experiences of other
      countries related to key issues such as quota allocation, aggregation limits,
      transferability, cost recovery, and resource sustainability when designing ITQ
      and other LAP systems. It is also important to explicitly identify economic and
      social objectives and then carefully design ITQ regimes to meet these objectives.

PMID- 18324344
TI  - Incidence and risk factors for hospital-acquired pneumonia after surgery for
      gastric cancer: results of prospective surveillance.
AB  - BACKGROUND: Postoperative hospital-acquired pneumonia (HAP) is recognized as a
      major risk associated with surgery. Although upper abdominal surgery is known to
      have the highest incidence of postoperative HAP, little is known about the risk
      factors that contribute to HAP after gastric cancer surgery. The aim of this
      study was to determine the incidence and risk factors for HAP after elective
      surgery for gastric cancer. METHODS: We conducted prospective surveillance of all
      elective gastric resections by surgeons in ten affiliated hospitals, including
      ours, from May 2001 to May 2005. The outcome of interest was postoperative HAP.
      Univariate and multivariate analyses were performed to determine the predictive
      significance of variables in gastric cancer surgery. RESULTS: A total of 529
      patients undergoing elective operations for gastric cancer were admitted to the
      program. Postoperative HAP was identified in 20 patients (3.6%). Univariate and
      multivariate analyses showed that male gender and intra- and/or postoperative
      blood transfusion were independently predictive of postoperative HAP.
      CONCLUSIONS: Male gender and intra- and/or postoperative blood transfusion were
      independent risk factors for the development of HAP after elective resection of
      gastric cancer. Surgeons should keep these risk factors in mind when managing
      postoperative patients.

PMID- 18324345
TI  - Can a lightbulb sestamibi SPECT accurately predict single-gland disease in
      sporadic primary hyperparathyroidism?
AB  - BACKGROUND: Technetium-99m sestamibi scintigraphy with single photon emission
      computed tomography (SPECT) is widely used to guide minimally invasive
      exploration in patients with sporadic primary hyperparathyroidism (SPH), although
      its sensitivity in multiglandular disease is limited. We examined the incidence
      of missed multiglandular disease and associated anatomic findings when sestamibi
      SPECT was positive for a single intense focus of delayed tracer uptake, termed a
      lightbulb scan (LBS). METHODS: Prospectively entered data from 764 patients with
      SPH treated with initial parathyroid exploration from March 5, 2000, to December
      31, 2006, were reviewed. A single radiologist performed blinded interpretation of
      585 available sestamibi SPECT images, classifying 167 (28.5%) patients with a
      LBS. Clinical findings were compared among LBS patients with a single adenoma
      (true positive) and LBS patients with multiglandular disease (false negative).
      RESULTS: One hundred fifty of 167 (89.8%) LBS patients had a single adenoma and 3
      (1.8%) had carcinoma. Multiglandular disease was anatomically present in 14 of
      167 (8.4%) LBS patients compared with 60 of 418 (15.6%) non-LBS patients
      (p=0.05). Parathyroid hyperplasia occurred less frequently in LBS patients [5/167
      (3%)] compared with non-LBS patients [36/418 (8.6%)], (p=0.02), while double
      adenomas occurred equally often in LBS patients [9/167 (5.4%)] compared with non
      LBS patients [24/418 (5.7%)], (p=0.87). Double adenomas in LBS patients were more
      likely ipsilateral (7/9, p=0.005) and left-sided (7/7, p=0.008). LBS patients
      with multiglandular disease were more likely to have a history of neck
      irradiation, prior neck exploration, and concomitant thyroid pathology.
      CONCLUSIONS: In patients with SPH, sestamibi SPECT studies show a single bright
      focus of uptake in only 29% of patients. LBS findings do not exclude
      multiglandular disease. To avoid unacceptable rates of failure at initial
      parathyroid exploration, the expert surgeon should use validated adjuncts such as
      intraoperative PTH monitoring or four-gland exploration.

PMID- 18324346
TI  - Candidate diagnostic markers and tumor suppressor genes for adrenocortical
      carcinoma by expression profile of genes on chromosome 11q13.
AB  - BACKGROUND: The most common genetic change observed in adrenocortical carcinoma
      is loss of heterozygozity on chromosome 11q13. As genes on this chromosome may be
      important in the pathogenesis of adrenocortical carcinoma, we compared their
      expression profile between benign and malignant adrenocortical tissue. METHODS:
      We used the Affymetrix GeneChip (U133 plus 2.0) array in 54 adrenocortical tumors
      (11 carcinoma and 43 benign). Differential gene expression was defined as a
      twofold higher or lower gene expression level (p<0.05). Differentially expressed
      genes on microarray analysis were validated by real-time quantitative reverse
      transcriptase polymerase chain reaction (RT-PCR). The area under the receiver
      operating characteristic (ROC) curve (AUC) was used to determined the diagnostic
      accuracy of the differently expressed genes for distinguishing benign from
      malignant tumors. RESULTS: We found 25 of the 314 genes on chromosome 11q13 to be
      differentially expressed between adrenocortical carcinoma and benign
      adrenocortical tumor. All 25 were downregulated in adrenocortical carcinoma by 2
      fold to 4.8-fold; 21 were validated to be differentially expressed by RT-PCR
      (Pearson's coefficient>0.5). Six genes (SERPING1, MRPL48, TM7SF2, DDB1, NDUSF8,
      PRDX5) validated by RT-PCR were significantly differentially expressed between
      benign and malignant adrenocortical tumors (p<0.05) with an overall accuracy of
      89% for SERPING1, 91% for MRPL48, 87% for TM7SF2, 88% for DDB1, 91% for NDUFS8,
      and 89% for PRDX5. The AUC was 0.89 for the combination of SERPING1, MRPL48,
      TM7SF2, DDB1, and NDUFS8. CONCLUSIONS: We have identified 25 genes located on
      chromosome 11q13 that are downregulated in adrenocortical carcinoma and may be
      candidate tumor suppressor genes. Six of these genes were good diagnostic markers
      for distinguishing adrenocortical carcinoma from adenoma.

PMID- 18324347
TI  - Surgery and radiofrequency ablation for treatment of liver metastases from midgut
      and foregut carcinoids and endocrine pancreatic tumors.
AB  - BACKGROUND: Many neuroendocrine tumors (NETs) have a tendency to metastasize to
      the liver. In case of limited number of metastases, liver surgery or
      radiofrequency ablation (RFA) may result in apparently total clearance of
      metastases. However, it is not clear whether such therapy will provide symptom
      reduction or increased survival. METHODS: Seventy-three patients with foregut
      (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two
      patients with NETs without discernable origin were studied. Symptoms were
      evaluated using a Symptom Severity Score. Liver surgery was performed in 42
      operations and RFA on 205 lesions. RESULTS: Apparently total clearance of liver
      metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with
      midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of
      17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA
      and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no
      improvement of symptoms after surgical/RFA liver treatment, but eight patients
      had functioning EPT, and four of these reduced their biochemical markers by at
      least 50%. NETs with higher Ki67 index tended to recur more often. Complications
      occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.
      CONCLUSIONS: Treatment of liver metastases is successful in midgut carcinoid
      patients with limited liver metastases. Patients with foregut carcinoid and EPTs
      recur more often, possibly related to higher Ki67 index, and treatment of liver
      lesions less often reduces symptoms. Liver resections and RFA may be safely
      performed, and RFA is associated with few complications.

PMID- 18324348
TI  - Pasieka's parathyroid symptoms scores correlate with SF-36 scores in patients
      undergoing surgery for primary hyperparathyroidism.
AB  - BACKGROUND: Parathyroidectomy for primary hyperparathyroidism (PHPT) is expected
      to trigger an improvement in the quality of life. This has been demonstrated
      previously by using the SF-36 questionnaire, whose interpretation is difficult in
      routine clinical practice. As an alternative, the 13-item questionnaire developed
      by Pasieka et al. can be used to assess the severity of symptoms on a visual
      analogue from which a parathyroid assessment of symptoms score (PAS) can be
      calculated. The purpose of this study was to correlate results of these two
      assessment tools. METHODS: Prospective case-series study recruiting consecutive
      unselected patients who underwent successful parathyroidectomy for PHPT. SF
      36(v2) and Pasieka's questionnaires were collected before parathyroidectomy and
      at 3, 6, and 12 months postoperatively. RESULTS: Between November 2005 and
      December 2006, 101 patients were diagnosed with PHPT (30 men; aged 18-89 years).
      Preoperative PAS ranged 0-1040 and did not correlate with the severity of
      hypercalcemia (2.91+/-0.25; range, 2.56-3.4 mmol/l). Scores from the SF-36
      questionnaire were under the 50th percentile for the normal population in three
      domains (vitality, emotional role, and physical role). Minimally invasive
      parathyroidectomy was performed in 69 patients and bilateral cervical exploration
      in 32 patients. All were found to have a single parathyroid adenoma and were
      normocalcemic at 3-12 months after parathyroidectomy. At follow-up, there was a
      significant reduction of PAS from 460+/-257 preoperatively to 254+/-234 at 3
      months postoperatively (n=72), to 245+/-215 at 6 months (n=50), and 249+/-212 at
      12 months (n=63) (p<0.05, Student's t-test). There was a significant and
      persistent improvement in five domains of SF-36 questionnaire: bodily pain,
      general health, vitality, social functioning and mental health. Overall analysis
      of 244 assessments using both questionnaires demonstrated a negative correlation
      between increasing PAS and decreasing mental component scores and physical
      component scores of the SF-36 assessment (r2=0.372 and 0.301, respectively).
      CONCLUSIONS: Pasieka's parathyroid assessment of symptom scores (PAS) correlate
      with SF-36 questionnaire scores. Because PAS allows easier and faster analysis,
      we advocate that Pasieka's questionnaire should be integrated into the assessment
      of patients with PHPT as a reliable tool to identify symptomatic changes that
      correlate with improved quality of life.

PMID- 18324349
TI  - Direct linking of metabolism and gene expression in the proline utilization A
      protein from Escherichia coli.
AB  - The control of gene expression by enzymes provides a direct pathway for cells to
      respond to fluctuations in metabolites and nutrients. One example is the proline
      utilization A (PutA) protein from Escherichia coli. PutA is a membrane-associated
      enzyme that catalyzes the oxidation of L: -proline to glutamate using a flavin
      containing proline dehydrogenase domain and a NAD(+) dependent Delta(1)-pyrroline
      5-carboxylate dehydrogenase domain. In some Gram-negative bacteria such as E.
      coli, PutA is also endowed with a ribbon-helix-helix DNA-binding domain and acts
      as a transcriptional repressor of the proline utilization genes. PutA switches
      between transcriptional repressor and enzymatic functions in response to proline
      availability. Molecular insights into the redox-based mechanism of PutA
      functional switching from recent studies are reviewed. In addition, new results
      from cell-based transcription assays are presented which correlate PutA membrane
      localization with put gene expression levels. General membrane localization of
      PutA, however, is not sufficient to activate the put genes.

PMID- 18324350
TI  - Long-term follow-up of patients with IgA nephropathy treated with prednisolone
      and cyclophosphamide therapy.
AB  - BACKGROUND: Analyses of selected cases suggest that immunosuppressive treatment
      could reduce proteinuria and delay the progression of immunoglobulin A
      nephropathy (IgAN). The aim of this study was to examine the long-term
      effectiveness of this therapy on the clinical course of IgAN. We also examined
      the relationship between the efficacy of the treatment and the suppression of the
      serum immunoglobulin level. METHODS: Eighteen patients who were observed for more
      than 2 years after prednisolone and cyclophosphamide therapy were enrolled in
      this study. Their clinical and laboratory characteristics were recorded for 2-18
      years (mean 7.8 +/- 5.7 years). RESULTS: Of the 18 patients, 13 had remission of
      proteinuria. We observed the subsequent development of proteinuria in four
      patients. Fourteen patients had remission of hematuria, with five patients
      experiencing subsequent relapse of hematuria. The mean time from the treatment to
      the relapse of proteinuria or hematuria was 5.8 years. Serum immunoglobulins were
      suppressed by the combination therapy. Serum IgG and IgM recovered 6 months after
      the treatment, whilst the suppression of serum IgA lasted for 4 years. We found a
      positive correlation between the serum IgA level and the degree of proteinuria.
      CONCLUSION: This study indicates that long-term follow-up is essential in order
      to prove the long-term benefit of immunosuppressive therapy in patients with
      IgAN. Careful monitoring of the serum IgA level may be useful in the follow-up of
      patients with IgAN, especially when they are treated with immunosuppressive
      agents.

PMID- 18324351
TI  - Papillary renal cell carcinoma: clinicopathological characteristics in 40
      patients.
AB  - BACKGROUND: Two different subtypes of papillary renal cell carcinoma (PRCC) have
      so far been identified, type-1 with small cells and pale cytoplasm and type-2
      with large cells and eosinophilic cytoplasm. It has generally been accepted that
      type-1 tumors have favorable features in comparison with type-2 tumors,
      suggesting that these subtypes could be different clinicopathological entities,
      and, as a result, that the subtypes need to be characterized. Forty cases of
      PRCCs were reviewed, with special attention to the distinct clinicopathological
      difference and the response to cytokine therapy. METHODS: Thirty-five cases of
      PRCC diagnosed between January 1997 and August 2007 were reviewed. PRCCs were
      classified according to the criteria of Delahunt and Eble. RESULTS: Of these 40
      patients, 20 and 20 were diagnosed to be type-1 and type-2 PRCCs, respectively.
      No lymphatic or vascular invasion or distant metastasis were observed in patients
      with type-1 PRCC. The nuclear grade in all type-1 PRCCs was low grade. The
      nuclear grade (P <or= 0.01) and the positive rate of vascular invasion (P <or=
      0.05) was significantly higher in type-2 than in type-1 PRCCs. Distant metastasis
      was detected preoperatively in three patients with type-2 PRCC. One patient with
      metastatic type-2 PRCCs demonstrated a response to IL-2 therapy. CONCLUSION:
      PRCCs include two distinct morphological types of tumor and type-2 PRCCs tends to
      have unfavorable features in comparison with type-1 PRCCs. These results support
      the clinical basis for the need to perform morphological subtyping of PRCCs when
      clinically evaluating such patients.

PMID- 18324352
TI  - Influence of hydrodynamic interactions on lane formation in oppositely charged
      driven colloids.
AB  - The influence of hydrodynamic interactions on lane formation of oppositely
      charged driven colloidal suspensions is investigated using Brownian dynamics
      computer simulations performed on the Rotne-Prager level of the mobility tensor.
      Two cases are considered, namely sedimentation and electrophoresis. In the latter
      case the Oseen contribution to the mobility tensor is screened due to the
      opposite motion of counterions. The simulation results are compared to that
      resulting from simple Brownian dynamics where hydrodynamic interactions are
      neglected. For sedimentation, we find that hydrodynamic interactions strongly
      disfavor laning. In the steady state of lanes, a macroscopic phase separation of
      lanes is observed. This is in marked contrast to the simple Brownian case where a
      finite size of lanes was obtained in the steady state. For strong Coulomb
      interactions between the colloidal particles a lateral square lattice of
      oppositely driven lanes is stable similar to the simple Brownian dynamics. In an
      electric field, on the other hand, the behavior is found in qualitative and
      quantitative accordance with the case of neglected hydrodynamics.

PMID- 18324354
TI  - Expression of glioma-associated antigens in pediatric brain stem and non-brain
      stem gliomas.
AB  - We investigated the protein expression of three glioma-associated antigens (GAAs)
      in pediatric brain stem glioma (BSG) and non-brain stem glioma (NBSG) cases with
      a view to their possible use in immunotherapy. Expression of EphA2, IL-13Ralpha2
      and Survivin were studied by immunohistochemistry on paraffin-embedded tissues
      using a series of 15 BSG cases and 12 NBSG cases. Thirteen of 15 BSGs and all 12
      NBSGs expressed at least one of GAAs; and 7 BSGs and 9 NBSGs expressed at least
      two of these GAAs at higher levels than non-neoplastic brain. There was no
      association between the tumor grade and levels of GAA expression. Although many
      cases demonstrated diffuse expression of GAAs throughout specimens, partial or
      patchy expression was noted in a small number of cases, suggesting a need for
      targeting multiple GAAs in immunotherapy. These results suggest that EphA2, IL
      13Ralpha2 and Survivin are suitable targets for developing vaccine strategies for
      pediatric glioma.

PMID- 18324353
TI  - Curcumin: from ancient medicine to current clinical trials.
AB  - Curcumin is the active ingredient in the traditional herbal remedy and dietary
      spice turmeric (Curcuma longa). Curcumin has a surprisingly wide range of
      beneficial properties, including anti-inflammatory, antioxidant, chemopreventive
      and chemotherapeutic activity. The pleiotropic activities of curcumin derive from
      its complex chemistry as well as its ability to influence multiple signaling
      pathways, including survival pathways such as those regulated by NF-kappaB, Akt,
      and growth factors; cytoprotective pathways dependent on Nrf2; and metastatic and
      angiogenic pathways. Curcumin is a free radical scavenger and hydrogen donor, and
      exhibits both pro- and antioxidant activity. It also binds metals, particularly
      iron and copper, and can function as an iron chelator. Curcumin is remarkably non
      toxic and exhibits limited bioavailability. Curcumin exhibits great promise as a
      therapeutic agent, and is currently in human clinical trials for a variety of
      conditions, including multiple myeloma, pancreatic cancer, myelodysplastic
      syndromes, colon cancer, psoriasis and Alzheimer's disease.

PMID- 18324355
TI  - In vitro-in vivo correlation on delivery of drug candidates to articular
      cartilage.
AB  - PURPOSE: In the treatment of osteoarthritis (OA), some of the therapeutic
      approaches require delivery of drug(s) to the diseased cartilage. Presence of
      adequate drug levels in the cartilage is one of the important criteria in
      selection and ranking of lead compounds. The purpose of this study was to
      investigate the correlation in cartilage compound levels between in vitro
      experiments and in vivo animal studies. MATERIALS AND METHODS: Bovine cartilage
      samples were incubated with test compounds of various concentrations in a culture
      medium, in the absence or presence of 25 mg/ml of serum albumin which served as
      an artificial synovial fluid (SF). The test compounds were also dosed to rabbits,
      the animal model used for efficacy studies, over a six-week treatment period.
      Test article concentrations in plasma, SF, and cartilage were determined by
      LC/MS/MS analysis. RESULTS AND CONCLUSIONS: A correlation in cartilage drug
      concentration was observed between in vitro and in vivo studies. Plasma protein
      binding and the test article's affinity to cartilage were the major determining
      factors for drug delivery to cartilage in vivo.

PMID- 18324356
TI  - Dissociated invasively growing cancer cells with NF-kappaB/p65 positivity after
      radiotherapy: a new marker for worse clinical outcome in rectal cancer?
      Preliminary data.
AB  - Objectives Nuclear factor-kappaB (NF-kappaB), especially p65 subunit, seems to be
      associated with origin and progression of cancer. The aim of the study was to
      determine expression of NF-kappaB/p65 in rectal cancer patients before and after
      radiotherapy as well as to assess the relationship between NF-kappaB/p65
      expression, other tumor characteristics, and disease progression. Further aim was
      to evaluate whether expression of NF-kappaB/p65 in tumor tissue may serve as a
      predictive marker of patient outcome. Patients and methods Twenty-five patients
      with rectal cancer undergoing pre-operative radiotherapy were included in the
      study. Unirradiated rectal cancer specimens were obtained from diagnostic
      colonoscopy. Irradiated rectal cancer specimens were obtained from surgically
      removed part of the rectum with the tumor. NF-kappaB/p65 expression was
      determined by immunohistochemistry. Results Cytoplasmic positivity in cancer
      cells and nuclear positivity in lymphocytes were detected. In post-radiotherapy
      specimens single tumor cells or small clones of them deeply infiltrating the wall
      of the rectum, that were characterized by high NF-kappaB/p65 expression, were
      found. Patients with presence of these cells in post-radiotherapy specimens have
      worse clinical outcome in terms of overall survival and disease-free interval.
      Conclusion While the NF-kappaB/p65 positive staining of the epithelial cells did
      not have any clinical implications in this study, it may be of clinical
      significance in the future. Residual invasively growing cancer cells with high NF
      kappaB/p65 positivity found in specimens after radiotherapy and surgery may be
      used to find what patients have a worse outcome. Thus, patients being at risk of
      cancer progression and requiring more aggressive anti-cancer therapy may be
      identified.

PMID- 18324357
TI  - Actin cytoskeletal mediators of motility and invasion amplified and overexpressed
      in head and neck cancer.
AB  - Coordinated regulation of the actin cytoskeleton is central to cell motility,
      invasion and metastasis. Head and neck squamous cell carcinoma (HNSCC) is a
      highly invasive disease displaying frequent lymph node metastasis, compounding
      patient management. HNSCC progression is characterized by frequent amplification
      of chromosome segments 3q26-29, 8q23-24 and 11q13, events that are associated
      with poor patient outcome. The relative frequency of these amplification events
      and correlation with invasive disease raises the potential that these regions
      harbor actin regulatory genes important in facilitating reorganization of the
      actin cytoskeleton to promote tumor invasion. Identification of the actin
      cytoskeletal regulatory genes located within the 3q26-29, 8q23-24 and 11q13
      amplicons will provide an important first step towards the comprehensive
      understanding of the molecular events that govern invasion and metastasis in
      HNSCC and other tumors containing these amplifications. We utilized Ensembl
      MartView to conduct a gene mining analysis within chromosome segments 3q26-29,
      8q23-24 and 11q13 to identify known and predicted regulators of actin-based cell
      movement, tumor invasion and metastasis. All examined chromosomal regions contain
      genes known that regulate the actin cytoskeleton, with several (PI3-kinase alpha,
      focal adhesion kinase (FAK) and cortactin) known to promote invasion in HNSCC and
      other carcinomas. Additional genes known to regulate motility and invasion were
      also identified. Amplification of chromosome 3q26-29, 8q23-24 and 11q13 therefore
      results in known or predicted overexpression of several key mediators that can
      act alone or potentially act in concert to promote actin-based cell invasion in
      HNSCC and other cancer types.

PMID- 18324358
TI  - Targeting the EGFR, VEGFR, and PDGFR on colon cancer cells and stromal cells is
      required for therapy.
AB  - Immunohistochemical analysis of human colon cancers growing in the cecal walls of
      nude mice revealed that epidermal growth factor receptor (EGFR) and vascular
      endothelial growth factor receptor 2 (VEGFR2) were expressed by different tumor
      cells and tumor-associated endothelial cells, whereas platelet-derived growth
      factor receptor (PDGFR)beta was expressed by tumor-associated endothelial cells
      and pericytes. We hypothesized that treatment of nude mice with AEE788 (an
      inhibitor of EGFR and VEGFR phosphorylation) and STI571 (an inhibitor of
      PDGFRbeta phosphorylation) combined with irinotecan would overcome the
      intratumoral heterogeneity of these growth factors and efficiently inhibit colon
      cancer growth and metastasis. We implanted HT29 and KM12SM cells into the cecal
      walls of nude mice. Two weeks later, the mice were treated with oral vehicle
      solution; oral AEE788, oral STI571, or intraperitoneal injection of irinotecan as
      single agents; or the various combinations of these agents. We then assessed the
      mice for tumor growth and metastasis. Immunohistochemical analyses revealed that
      oral AEE788 suppressed proliferation and increased apoptosis of tumor cells and
      tumor-associated endothelial cells. Oral STI571 increased apoptosis of tumor
      associated endothelial cells and pericytes. The combination of AEE788, STI571,
      and irinotecan produced the greatest inhibition of primary tumor growth and
      metastasis. Collectively, these data demonstrate that only targeting multiple
      tyrosine kinase receptors on colon cancer cells and tumor-associated stromal
      cells can overcome the effects of biologic heterogeneity for resistance to
      treatment and has the potential to improve therapeutic outcome for patients with
      this disease.

PMID- 18324359
TI  - Troponin I in the intensive care unit setting: from the heart to the heart.
AB  - When measured in the plasma, cardiac troponins T (cTnT) and I (cTnI) are
      considered to be highly specific markers of myocardial cell damage; however,
      research has demonstrated that troponin elevation may associated with causes
      other than coronary artery disease. In the intensive care unit (ICU) setting,
      increased cTnI levels are quite common findings and when documented, even on
      admission, intensivists should bear in mind that this laboratory finding holds a
      prognostic role independent of the reason for ICU admission. The mechanism(s)
      (such as demand ischemia, myocardial strain, etc.) and not simply the cause
      (i.e., renal failure) of the increment in serum cTnI should be investigated to
      better tailor the therapeutical regimen in the single patient. In this review, we
      therefore consider the nonthrombotic causes of troponin elevation in the critical
      setting.

PMID- 18324360
TI  - A 48-year-old woman with dyspnoea on exertion, anemia and thrombocytopenia.

PMID- 18324361
TI  - Neutropenic patient with fever and abdominal pain.

PMID- 18324362
TI  - Opportunities, challenges, and caveats of successful molecular imaging of
      cardiovascular diseases.

PMID- 18324363
TI  - Cardiovascular diseases as target for imaging.
AB  - Recent pathophysiological findings have lead to new concepts to identify patients
      at risk for cardiovascular disease using systemic serum markers or new imaging
      methodology. New probe technology and progress in imaging techniques have set the
      base for development of molecular imaging concepts in the cardiovascular systems.
      The aim of these new imaging techniques is the detection of active biological
      processes in cardiovascular systems combining specific probes with contrast
      agents for MRI, SPECT or PET. There are promising strategies mostly in
      preclinical tests, which will prove clinical applicability in the near future.

PMID- 18324364
TI  - MR-optical imaging of cardiovascular molecular targets.
AB  - Our understanding of the intricate inflammation biology underlying
      atherosclerosis is rapidly progressing. Molecular imaging strategies, harnessing
      this body of knowledge, have been developed to visualize some key cellular and
      molecular events in plaque evolution and vulnerability. Here, we discuss recent
      advances in magnetic resonance and fluorescence imaging of key biomarkers
      including adhesion molecules, inflammatory cells, and enzyme activity. We discuss
      strengths and limitations of respective imaging technologies, and comment on the
      potential of multi-modality imaging approaches.

PMID- 18324365
TI  - Annexin A5: an imaging biomarker of cardiovascular risk.
AB  - Apoptosis, a form of programmed cell death (PCD), plays an important role in the
      initiation and progression of a number of cardiovascular disease, such as heart
      failure, myocardial infarction, and atherosclerosis. One of the most prominent
      characteristics of apoptosis is the externalisation of phosphatidylserine (PS), a
      plasma cell membrane phospholipid, which in healthy cells only is present on the
      inner leaflet of the plasma cell membrane. Annexin A5, a 35 kD plasma protein,
      has strong affinity for PS in the nano-molar range. Through the coupling of
      Annexin A5 to contrast agents, visualization of apoptotic cell death in vivo in
      animal models and in patients has become feasible. These imaging studies have
      provided novel insight into the extent and kinetics of apoptosis in
      cardiovascular disease. Furthermore, Annexin A5 imaging has proven to be a
      suitable imaging biomarker for the evaluation of cell death modifying compounds
      and plaque stabilizing strategies. Recent insight in PS biology has shown that PS
      externalisation not only occurs in apoptosis, but is also observed in activated
      macrophages and stressed cells. In addition, it has been shown that Annexin A5
      not only binds to exteriorized PS, but is also internalized through an Annexin A5
      specific mechanism. These latter findings indicate that Annexin A5 imaging is not
      exclusively valuable for apoptosis detection, but can also be used to visualize
      inflammation and cell stress. This will open novel opportunities for imaging and
      drug delivery strategies. In this review we will discuss the introduction of
      Annexin A5 in preclinical and clinical imaging studies and provide an outlook on
      novel opportunities of Annexin A5 based targeting of PS.

PMID- 18324366
TI  - Imaging of stem cells using MRI.
AB  - The administration of exogenous stem cells offers promise to regenerate many
      damaged organs. However, failures of these cellular therapies could be related to
      many issues, such as the type of stem cell, the dose of cellular therapeutic,
      dosing regime, and mode of delivery. The recent ability to directly label stem
      cells with magnetic resonance (MR) contrast agents provides a simple, straight
      forward manner to monitor accurate cell delivery and track stem cells non
      invasively in a serial manner. Provided here is an overview of the currently
      available MR-labeling methods, including direct non-specific labeling with
      contrast agents, indirect specific labeling with contrast agents, labeling with
      MRI reporter genes, and fluorine hot spot labeling. Several of these approaches
      have now been applied successfully in preclinical animal models of cardiovascular
      disease. Once properly implemented, future clinical trials may benefit greatly
      from imaging stem cells with MRI.

PMID- 18324367
TI  - Contrast agents for MRI.
AB  - Molecular imaging is a rapidly growing field with the potential to revolutionize
      cardiovascular medicine by shifting diagnostic focus from functional
      abnormalities which occur late in a disease process to the biochemical events
      which precipitate the earliest stages of disease. MRI is a modality well suited
      to this task as it allows a variety of contrast mechanisms for detection of
      epitopes of interest, as well as high-resolution anatomical localization and
      functional information. In this review, we discuss the widerange of available
      molecular MRI contrast agents and their application to diseases such as
      atherosclerosis, thrombus imaging, and stem cell tracking, along with
      opportunities for molecularly targeted drug delivery.

PMID- 18324368
TI  - Magnetic nanoparticles for MR imaging: agents, techniques and cardiovascular
      applications.
AB  - Magnetic nanoparticles (MNP) are playing an increasingly important role in
      cardiovascular molecular imaging. These agents are superparamagnetic and consist
      of a central core of iron-oxide surrounded by a carbohydrate or polymer coat. The
      size, physical properties and pharmacokinetics of MNP make them highly suited to
      cellular and molecular imaging of atherosclerotic plaque and myocardial injury.
      MNP have a sensitivity in the nanomolar range and can be detected with T1, T2,
      T2*, off resonance and steady state free precession sequences. Targeted imaging
      with MNP is being actively explored and can be achieved through either surface
      modification or through the attachment of an affinity ligand to the nanoparticle.
      First generation MNP are already in clinical use and second generation agents,
      with longer blood half lives, are likely to be approved for routine clinical use
      in the near future.

PMID- 18324369
TI  - (18)F-labelled cardiac PET tracers: selected probes for the molecular imaging of
      transporters, receptors and proteases.
AB  - Designated radiopharmaceuticals labelled with the prominent positron-emitter
      (18)F can be defined as molecular imaging probes for the examination of
      cardiovascular diseases at the cellular and subcellular level. Such molecular
      imaging agents representing radioindicators or radiotracers offer the opportunity
      to non-invasively trace their path and fate in the living organism by the
      scintigraphic technique, positron emission tomography (PET). The glucose analogue
      [(18)F]FDG is a widespread PET tracer and one of the earliest examples of a PET
      molecular imaging probe feasible to in vivo visualise glucose utilisation by a
      metabolic trapping mechanism. This short review is focussed on selected
      established (18)F-labelled PET tracers as well as (18)F-labelled radioligands in
      development that show the potential of being probes for the in vivo molecular
      imaging of proteins relevant in cardiovascular diseases such as receptors (i.e.
      beta-Adrenoceptors), transporters (i.e. NET and VMAT) and proteases (i.e. MMPs).

PMID- 18324370
TI  - Near-infrared fluorescent probes for imaging vascular pathophysiology.
AB  - Light in the near-infrared (NIR) region between 700-900 nm can penetrate deep
      into living tissue, thereby offering a unique opportunity to use near-infrared
      fluorescence (NIRF) imaging techniques to detect and visualize fluorescent probes
      in-vivo. In the past few years, many novel NIR fluorescent probes have been
      designed, synthesized and studied in a variety of disease conditions. Recent
      research has focused primarily on the class of cyanines dyes as non-specific
      agents and as part of specific NIR fluorescent probes. The publications reviewed
      herein discuss the characteristics of cyanine dyes and their conjugates and
      present examples for the application of these probes for imaging vascular
      pathophysiology.

PMID- 18324371
TI  - Structural and functional imaging by MRI.
AB  - Magnetic resonance imaging is one of the most exciting techniques for noninvasive
      molecular imaging of the cardiovascular system. The article will describe
      challenges, solutions and results of magnetic resonance plaque imaging ex-vivo,
      in the experimental animal and in patients.

PMID- 18324372
TI  - Imaging of the heart with computed tomography.
AB  - Imaging of the heart with computed tomography (CT) was already introduced in the
      1980Is and has meanwhile entered clinical routine as a consequence of the rapid
      evolution of CT technology during the last decade. In this review article, we
      give an overview on the technology and clinical performance of different CT
      scanner generations used for cardiac imaging, such as Electron Beam CT (EBCT),
      single-slice CT und multi-detector row CT (MDCT) with 4, 16 and 64 simultaneously
      acquired slices. We identify the limitations of current CT-scanners, indicate
      potential of improvement and discuss alternative system concepts such as CT with
      area detectors and dual source CT (DSCT).

PMID- 18324373
TI  - Ultrasonic imaging of molecular targets.
AB  - Today nuclear medicine is the only modality that is clinically successful in
      molecular imaging. However, other modalities compete with its excellent
      sensitivity in imaging molecular targets. In the last 10 years ultrasound imaging
      has shown the potential to provide sufficiently high sensitivity for the
      molecular imaging of vascular targets. These advances are based on the joint
      development of microbubble contrast media and the methods to image them with high
      sensitivity. Ultrasound-contrast-enhanced imaging strategies make use of the
      specific physical properties of microbubbles such as resonance, nonlinear
      oscillation, and collapse. The size of microbubbles limits their use to the
      vascular space. Thus, the main applications of ultrasound for molecular imaging
      are inflammation, thrombi, and angiogenesis, for which successful contrast
      enhancement has been achieved in animal models. Main molecular targets used to
      date include selectins, alpha(v)beta(3) or alpha(5)beta(1) integrins,
      glycoprotein (GP) IIb/IIIa, intracellular adhesion molecule ICAM-1, and vascular
      endothelial growth factor receptor VEGFR2. Results from animal studies indicate
      that ultrasound could play a major role in vascular molecular imaging for
      diagnosis and treatment monitoring. Additional effects of insonified microbubbles
      (e.g., opening of the blood-brain barrier or increased transfection efficiency in
      gene therapy) are attributed to the transient opening of cell membranes known as
      "sonoporation" and demonstrate further potential for integrated diagnosis and
      therapy.

PMID- 18324374
TI  - Optical imaging of vascular pathophysiology.
AB  - Pathophysiological processes in the vascular system are the major cause of
      mortality and disease. Atherosclerosis, an inflammatory process in arterial
      walls, can lead to formation of plaques, whose rupture can lead to thrombus
      formation, obstruction of vessels (thrombosis), reduction of the blood flow
      (ischemia), cell death in the tissue fed by the occluded vessel, and depending on
      the affected vessel, to myocardial infarction or stroke. Imaging techniques
      enabling visualization of the biological processes involved in this scenario are
      therefore highly desirable. In recent years, a number of reporter agents and
      reporter systems have been developed to visualize these processes using different
      imaging modalities including nuclear imaging techniques, such as positron
      emission tomography or single photon emission computed tomography, magnetic
      resonance imaging, and ultrasound. This article comprises a brief overview of
      optical imaging techniques, such as fluorescence imaging and bioluminescence
      imaging for the visualization of vascular pathophysiology.

PMID- 18324375
TI  - Combined imaging of molecular function and morphology with PET/CT and SPECT/CT:
      image fusion and motion correction.
AB  - Imaging of the cardiovascular system with a combination of positron emission
      tomography (PET) and computer tomography (CT) or with a combination of single
      photon emission computerized tomography (SPECT) and CT holds great promise for
      the future. Owing to the movement of the heart and the great vessels due to heart
      contraction and respiration this is, however, not straightforward. This article
      provides an overview over the principles of combined PET/CT or SPECT/CT imaging.
      It points out technical challenges inherent in imaging of cardiovascular system
      and presents possible solutions that allow for optimal fusion and motion
      correction of the combined molecular, functional and morphological image data.

PMID- 18324376
TI  - The future of molecular imaging in the clinic needs a clear strategy and a
      multidisciplinary effort.
AB  - Although advances in modern medicine do already and might provide even more new
      tools to prevent from life-threatening cardiovascular events in the future, the
      virtually unchanged high numbers of cardiovascular events suggest an unmet
      diagnostic challenge. Prevention of cardiovascular events, which are responsible
      for approximately 1/3 of all deaths in the industrialised societies, therefore
      needs new diagnostic tools, since current morphological and functional imaging
      approaches seem to fail in this respect.This article outlines the principle
      strategy and prerequisites to come up with a clinically relevant and successful
      molecular imaging technology in the future.

PMID- 18324377
TI  - Ultrasonic harmonic scalpel in total thyroidectomies.
AB  - INTRODUCTION: Haemostasis is very important in thyroid surgery. In conventional
      surgery, electrocoagulation and suture ligation are used for haemostasis; newer
      techniques include vessel clips, ultrasonic instruments and lasers. The aim of
      this prospective study was to compare the usage of the ultrasonic harmonic
      scalpel (UHS) with conventional procedures, in total thyroidectomies, for
      operation time, blood loss, usage of drain, cost, length of hospitalisation and
      complications. METHODS: We examined 104 patients who underwent bilateral total
      thyroidectomy. They were divided randomly into two groups. Patients in Group I
      (n=54) underwent operations using conventional techniques (electrocautery and
      suture ligation) while patients in Group II (n=50) underwent operations using the
      UHS. Operation time, number of ligatures used, blood loss, intra-operative
      complications, weight of the specimen, necessity of drain, postoperative seroma,
      bleeding, infection, transient or permanent hypocalcaemia, permanent recurrent
      laryngeal nerve palsy and length of hospitalisation were recorded. RESULTS: The
      operation time was significantly longer in Group I (conventional) (105+/-16
      minutes; mean+/-standard deviation) than Group II (UHS) (77.9+/-12.5 minutes;
      P<0.001). The mean blood loss was less in patients who were operated on with the
      UHS (25.3+/-10.2 g) than in patients operated on with conventional methods
      (59.5+/-33.9 g; P<0.001). The mean number of ligatures used in the UHS group was
      5.3, which was significantly fewer than the mean of 51.6 ligatures used in the
      conventional methods group (P<0.001). Drains were also used less in the UHS
      operations (12%-59%; P<0.001). CONCLUSION: Use of the UHS in thyroid surgery
      results in decreased operation time, drain usage and amount of bleeding and does
      not increase postoperative complications. The UHS is an effective, reliable and
      less expensive technique for thyroid surgery.

PMID- 18324378
TI  - Chitotriosidase activity in juvenile idiopathic arthritis.
AB  - Juvenile idiopathic arthritis (JIA) is an inflammatory joint disease of unknown
      etiology. The pathogenesis is driven by T and B cells. The role of macrophages
      remains unclear. Chitotriosidase belongs to the chitinase protein family and is
      secreted by activated macrophages. The chitinases are able to catalyze the
      hydrolysis of chitin or chitin-like substrates such as 4-methylumbelliferyl
      chitotrioside. Chitotriosidase activity was determined using the substrate 4
      methylumbelliferyl beta-DNN'N''-triacetylchitotrioside (4-MU-TCT, SIGMA Chemical
      Co.). The substrate and serum were incubated with the serum in a
      citrate/phosphate buffer. The reaction was stopped by adding a buffer (Na2CO3).
      The fluorescence of 4-methylumbelliferone was evaluated by fluorimeter at
      excitation 360 nm and emission 450 nm. We report about chitotriosidase
      measurements in patients with JIA. The chitotriosidase level in synovial fluid
      was up to approximately 1,000 nmol/(h ml) at disease onset before therapy. The
      level in the sera was below 600 nmol/(h ml). Serum chitotriosidase levels could
      represent the activity of macrophages in the synovial fluid in JIA.

PMID- 18324379
TI  - Can Islamic prayers benefit spondyloarthritides? Case report of a patient with
      ankylosing spondylitis and increased spinal mobility after an intensive regimen
      of Islamic prayer.
AB  - A 35-year-old Arab male had severe Ankylosing Spondylitis for 10 years with
      syndesmophyte formation in the lumbar spine, decreased spinal mobility (modified
      Schoeber's test of 0.5 cm), BASDAI of 4, and BASFI score of 6. He was initially
      started on non- steroidal anti-inflammatory medications (NSAID) and a regular
      swimming program as well as physiotherapy. Due to lack of response he was started
      on Etanercept monotherapy. After 1 month his modified Schober's had improved to 1
      cm, BASDAI to 2, and BASFI to 1. At 5 months after starting treatment, there was
      no further improvement. Patient embarked on an intensive regimen of Islamic
      prayers during the month of Ramadan, lasting approximately 2 h daily, for 1
      month. At the end of 1 month he had improved spinal mobility with a modified
      schober's test of 2.5 cm and stable BASFI scores. Islamic prayers consist of
      several postures, including stretching, bending and kneeling. Further study is
      needed, but Muslim patients can be easily motivated to perform long hours of
      Islamic prayers, and this can offer benefits, when used in conjunction with
      conventional treatments, for spondyloarthritis.

PMID- 18324380
TI  - [Prize for the best contribution to continuing education. 4th Springer CME Award
      Der Internist].

PMID- 18324381
TI  - [A 67-year-old patient with recurrent hypoglycemia].
AB  - A 67 year old female patient was admitted to our clinic with recurrent
      hypoglycemia in December 2006. Laboratory findings revealed an elevated insulin,
      and C-peptide. Imaging techniques revealed a tumor of the pancreas involving the
      spleen with metastases of the liver, expressing somatostatin receptors.
      Ultrasound-guided biopsy was performed and confirmed the suspected insulinoma.
      Since the hypoglycemias could not sufficiently be controlled by subcutaneous
      administration of octreotide and by oral glucose intake, surgical debulking was
      performed in a palliative intention. After resection the patient was free of
      hypoglycemia. In case of diagnosed insulinoma, underlying MEN (multiple endocrine
      neoplasia) should be considered. Excision of the tumor is recommended in patients
      with benign solitary insulinomas. If complete excision is impossible, there are
      several therapeutic options that aim at preventing hypoglycemia. Thus, in
      contrast to other extended tumors, surgery is reasonable in malignant insulinoma
      even in case of metastatic disease.

PMID- 18324382
TI  - [Drug-induced eosinophilic pneumonia].
AB  - Eosinophilic pneumonia is a lung disorder characterized by eosinophilic pulmonary
      infiltration and blood eosinophilia. It can be caused by a variety of drugs.
      Especially in mild forms and in chronically neurologically ill patients, it can
      be difficult to spot. We report the case of a 46-year-old woman suffering from
      multiple sclerosis who developed nitrofurantoin-induced eosinophilic pneumonia.

PMID- 18324383
TI  - Separate loci underlie resistance to root infection and leaf scorch during
      soybean sudden death syndrome.
AB  - Soybean [Glycine max (L.) Merr.] cultivars show differences in their resistance
      to both the leaf scorch and root rot of sudden death syndrome (SDS). The syndrome
      is caused by root colonization by Fusarium virguliforme (ex. F. solani f. sp.
      glycines). Root susceptibility combined with reduced leaf scorch resistance has
      been associated with resistance to Heterodera glycines HG Type 1.3.6.7 (race 14)
      of the soybean cyst nematode (SCN). In contrast, the rhg1 locus underlying
      resistance to Hg Type 0 was found clustered with three loci for resistance to SDS
      leaf scorch and one for root infection. The aims of this study were to compare
      the inheritance of resistance to leaf scorch and root infection in a population
      that segregated for resistance to SCN and to identify the underlying quantitative
      trait loci (QTL). "Hartwig", a cultivar partially resistant to SDS leaf scorch,
      F. virguliforme root infection and SCN HG Type 1.3.6.7 was crossed with the
      partially susceptible cultivar "Flyer". Ninety-two F5-derived recombinant inbred
      lines and 144 markers were used for map development. Four QTL found in earlier
      studies were confirmed. One contributed resistance to leaf scorch on linkage
      group (LG) C2 (Satt277; P = 0.004, R2 = 15%). Two on LG G underlay root infection
      at R8 (Satt038; P = 0.0001 R2 = 28.1%; Satt115; P = 0.003, R2 = 12.9%). The
      marker Satt038 was linked to rhg1 underlying resistance to SCN Hg Type 0. The
      fourth QTL was on LG D2 underlying resistance to root infection at R6 (Satt574; P
      = 0.001, R2 = 10%). That QTL was in an interval previously associated with
      resistance to both SDS leaf scorch and SCN Hg Type 1.3.6.7. The QTL showed
      repulsion linkage with resistance to SCN that may explain the relative
      susceptibility to SDS of some SCN resistant cultivars. One additional QTL was
      discovered on LG G underlying resistance to SDS leaf scorch measured by disease
      index (Satt130; P = 0.003, R2 = 13%). The loci and markers will provide tagged
      alleles with which to improve the breeding of cultivars combining resistances to
      SDS leaf scorch, root infection and SCN HG Type 1.3.6.7.

PMID- 18324385
TI  - The common SLC30A8 Arg325Trp variant is associated with reduced first-phase
      insulin release in 846 non-diabetic offspring of type 2 diabetes patients--the
      EUGENE2 study.
AB  - AIMS/HYPOTHESIS: A recent genome-wide association study identified the SLC30A8
      rs13266634 polymorphism encoding an Arg325Trp polymorphism in the zinc
      transporter protein member 8 (ZnT-8) to be associated with type 2 diabetes. Here,
      we investigate whether the polymorphism is related to altered insulin release in
      response to intravenous and oral glucose loads in non-diabetic offspring of type
      2 diabetic patients. METHODS: We genotyped SLC30A8 rs13266634 in 846 non-diabetic
      offspring of type 2 diabetic patients from five different white populations:
      Danish (n = 271), Finnish (n = 217), German (n = 149), Italian (n = 109) and
      Swedish (n = 100). Participants were subjected to both IVGTTs and OGTTs, and
      measurements of insulin sensitivity. RESULTS: Homozygous carriers of the major
      type 2 diabetes C risk-allele showed a 19% decrease in first-phase insulin
      release (0-10 min) measured during the IVGTT (CC 3,624 +/- 3,197; CT 3,763 +/-
      2,674; TT 4,478 +/- 3,032 pmol l(-1) min(-1), mean +/- SD; p = 0.007). We found
      no significant genotype effect on insulin release measured during the OGTT or on
      estimates of insulin sensitivity. CONCLUSIONS/INTERPRETATION: Of European non
      diabetic offspring of type 2 diabetes patients, 46% are homozygous carriers of
      the Arg325Trp polymorphism in ZnT-8, which is known to associate with type 2
      diabetes. These diabetes-prone offspring are characterised by a 19% decrease in
      first-phase insulin release following an intravenous glucose load, suggesting a
      role for this variant in the pathogenesis of pancreatic beta cell dysfunction.

PMID- 18324386
TI  - Reduced EDHF responses and connexin activity in mesenteric arteries from the
      insulin-resistant obese Zucker rat.
AB  - AIMS/HYPOTHESIS: The objective of this study was to examine the effect of insulin
      resistance on endothelium-derived hyperpolarising factor (EDHF) and small
      mesenteric artery endothelial function using 25-week-old insulin-resistant obese
      Zucker rats (OZRs) and lean littermate control rats (LZRs). The involvement of
      gap junctions and their connexin subunits in the EDHF relaxation response was
      also assessed. METHODS: Mesenteric arteries were evaluated using the following
      assays: (1) endothelial function by pressure myography, with internal diameter
      recorded using video microscopy; (2) connexin protein levels by western blotting;
      and (3) Cx mRNA expression by real-time PCR. RESULTS: Relaxations in response to
      acetylcholine were significantly smaller in mesenteric arteries from the OZRs
      than the LZRs, whereas there was no difference in relaxations in response to
      levcromakalim. Responses to acetylcholine were not altered by nitric oxide
      inhibitors, but were abolished by charybdotoxin in combination with apamin, which
      blocked the EDHF component of the response. 40Gap27 significantly attenuated the
      response to acetylcholine in the LZRs, but had no effect in the OZRs. Connexin 40
      protein and Cx40 mRNA levels in mesenteric vascular homogenates were
      significantly smaller in the OZRs than in the LZRs, with no difference in
      connexin 43 or Cx43 mRNA levels. CONCLUSIONS/INTERPRETATION: These findings
      demonstrate that endothelial dysfunction in mesenteric arteries from the insulin
      resistant OZRs can be attributed to a defect in EDHF. The results also suggest
      that the defective EDHF is at least partly related to an impairment of connexin
      40-associated gap junctions, through a decrease in connexin 40 protein and Cx40
      mRNA expression in the OZRs.

PMID- 18324387
TI  - [Diagnosis and treatment of osteochondral lesions of the talus].
AB  - Delayed diagnosis of osteochondral lesions of the talus is common; acute
      osteochondral injuries to the talar dome frequently go unrecognized. While acute
      lesions may be repaired, typically the focus of operative treatment for
      osteochondral lesions is on: (a) debridement and drilling/microfracture (leading
      to filling of the defect with fibrocartilage) or (b) salvage procedures,
      including osteochondral autograft transfer system and autologous chondrocyte
      implantation (potentially leading to resurfacing of the defect with hyaline
      cartilage). In this article, we review current trends in preoperative assessment,
      defining indications and surgical management of osteochondral lesions of the
      talus.

PMID- 18324388
TI  - [Conservative therapy of cartilage defects of the upper ankle joint].
AB  - Cartilage defects of the upper ankle joint reflect the problem that great force
      is transmitted and balanced out over a relatively small surface area. As a
      pathophysiological factor, cartilage-bone contusions play a significant role in
      the development of cartilage defects of the upper ankle joint. Physiotherapeutic
      procedures belong to the standard procedures of conservative therapy. The use and
      selection of the type of therapy is based on empirical considerations and
      experience and investigations on effectiveness of particular therapies are
      relatively rare. At present a symptom-oriented therapy of cartilage defects of
      the upper ankle joint seems to be the most sensible approach. It can be assumed
      that it makes sense that the symptomatic treatment of cartilage defects or
      initial stages of arthritis also includes the subsequent symptoms of pain,
      irritated condition and limited function. This leads to starting points for
      physiotherapy with respect to pain therapy, optimisation of pressure
      relationships, avoidance of pressure points, improvement of diffusion and
      pressure release. In addition to the differential physiotherapeutic findings, the
      determination of a curative, preventive or rehabilitative procedure is especially
      important. In physical therapy special importance is placed on a scheduled serial
      application corresponding to the findings, employing the necessary methods, such
      as physiotherapy, sport therapy, medical mechanics, manual therapy, massage,
      electrotherapy and warmth therapy. From this the findings-related therapy is
      proposed as a practical therapy concept: locomotive apparatus pain therapy,
      optimisation of pressure relationships, improvement of diffusion and decongestion
      therapy. Therapy options have been selected base on the current literature and
      are summarised in tabular form. The art of symptomatic therapy of cartilage
      defects of the upper ankle joint does not lie in the multitude of sometimes
      speculative procedures, but in the targeted selection of a therapy regime based
      on the therapeutic goal, a corresponding application dose and serial design.

PMID- 18324389
TI  - [The infected implant].
AB  - The periprosthetic infection is a permanent risk and a severe complication in
      joint arthroplasty. Raising numbers of cases, unsatisfactory results of treatment
      and high cost urge to sufficient prophylactic behaviour in primary surgery and
      research for new treatment strategies. In the future antibiotic coating of the
      implants and influence on biofilm could possibly be established. Disciplined
      early diagnostic measures and rational actions following the established concepts
      are able to create better results and reduce the extreme high costs.

PMID- 18324390
TI  - Anxiolytic-like effects of morphine and buprenorphine in the rat model of fear
      potentiated startle: tolerance, cross-tolerance, and blockade by naloxone.
AB  - RATIONALE: Morphine and buprenorphine have analgesic and anxiolytic-like
      properties. While their analgesic effects have been well characterized, their
      anxiolytic-like properties have not. OBJECTIVES: Effects of acute morphine and
      buprenorphine on the expression of acoustic fear-potentiated startle (FPS) and
      naloxone pretreatment were assessed. Effects of chronic morphine and
      buprenorphine on tolerance, cross-tolerance, and withdrawal were also examined.
      MATERIALS AND METHODS: Fear-conditioned rats were given subcutaneous drug
      treatment immediately before testing for FPS. Experiment 1, rats were
      administered morphine (0.03, 0.25, 0.63, 2.5, or 10 mg/kg) or buprenorphine
      (0.004, 0.0075, 0.015, 0.03, or 0.25 mg/kg). Experiment 2, rats were given saline
      or naloxone (0.5 mg/kg) and 5 min later given saline, morphine (2.5 mg/kg), or
      buprenorphine (0.03 mg/kg). Experiment 3, rats received once-daily injections of
      saline, morphine (10 mg/kg), or buprenorphine (0.25 mg/kg) for 7 days.
      Immediately before testing, saline-treated rats were given saline, morphine (2.5
      mg/kg), or buprenorphine (0.03 mg/kg), morphine-treated rats were given morphine
      (2.5 mg/kg) or buprenorphine (0.03 mg/kg), and buprenorphine-treated rats were
      given buprenorphine (0.03 mg/kg) or morphine (2.5 mg/kg). Tolerance and cross
      tolerance in analgesia were assessed via the tail-flick test, as were naloxone
      precipitated withdrawal. RESULTS: Morphine and buprenorphine had parallel dose
      response curves in blocking FPS, with buprenorphine 40 times more potent than
      morphine. Naloxone reversed these effects. Morphine and buprenorphine showed
      tolerance and cross-tolerance in their anxiolytic-like and analgesic effects.
      Chronic buprenorphine produced less withdrawal than chronic morphine.
      CONCLUSIONS: Cross-tolerance between morphine and buprenorphine suggests a common
      receptor mediating their anxiolytic-like and analgesic effects.

PMID- 18324391
TI  - Characterization of a titanium(IV)-porphyrin complex as a highly sensitive and
      selective reagent for the determination of hydrogen peroxide: a computational
      chemistry approach and a critical review.
AB  - The Ti-TPyP reagent, i.e. an acidic aqueous solution of the oxo[5,10,15,20
      tetra(4-pyridyl)porphyrinato] titanium(IV) complex, TiO(tpyp), was developed as a
      highly sensitive and selective spectrophotometric reagent for determination of
      traces of hydrogen peroxide. Using this reagent, determination of hydrogen
      peroxide was performed by flow-injection analysis with a detection limit of 0.5
      pmol per test. The method was actually applied to determination of several
      constituents of foods, human blood, and urine mediated by appropriate oxidase
      enzymes. The reaction specificity of the TiO(tpyp) complex for hydrogen peroxide
      was clarified from the viewpoint of the reaction mechanisms and molecular
      orbitals based on ab initio calculations. The results provided a well-grounded
      argument for determination of hydrogen peroxide using the Ti-TPyP reagent
      experimentally. This review deals with characterization of the high sensitivity
      and reaction specificity of the Ti-TPyP reagent for determination of hydrogen
      peroxide, to prove its reliability in analytical applications.

PMID- 18324392
TI  - The relationship between poor sleep and inhibitory functions indicated by event
      related potentials.
AB  - The present study focused on the relationship between normal variations of sleep
      and inhibitory functions as reflected in event-related potentials. For this
      reason one night of 21 healthy participants was analysed. After waking up all
      participants completed a visual Go/Nogo task. On the basis of a sleep disturbance
      index (SDI) the participants were separated into 8 SDI-good and 13 SDI-poor
      sleepers using a cluster analysis. The results showed that Nogo-N2 amplitude was
      smaller and Nogo-P3 latency longer in SDI-poor sleepers. Moreover, Go-P3
      amplitude was smaller in SDI-poor sleepers. Performance parameters were not
      influenced by poor sleep. We concluded that poor sleep specifically affects the
      intensity of pre-motor inhibitory processes (Nogo-N2 amplitude), the speed to
      inhibit a motor response (Nogo-P3 latency) and the intensity of task-relevant
      information processing (Go-P3 amplitude). In further studies, it should be
      explored under which conditions such subliminal deficits also become relevant for
      overt behaviour.

PMID- 18324393
TI  - Abnormal course of the vertebral artery at the craniovertebral junction in
      patients with Down syndrome visualized by three-dimensional CT angiography.
AB  - INTRODUCTION: We determined the incidence of vertebral artery (VA) anomalies at
      the craniovertebral junction (CVJ) in patients with Down syndrome, and
      characterized the VA anomalies. METHODS: The course of the VA in 46 consecutive
      patients who were due to undergo posterior arthrodesis surgery at the CVJ were
      evaluated by three-dimensional CT angiography (3DCTA). Included were five
      patients with Down syndrome who suffered from myelopathy due to atlantoaxial
      subluxation. All five patients with Down syndrome also had a simultaneous
      congenital skeletal anomaly, either os odontoideum or ossiculum terminale.
      RESULTS: Of the five patients with Down syndrome, three had VA anomalies at the
      CVJ, two had fenestration and one had a persistent first intersegmental artery.
      Of the other 41 patients without Down syndrome, five had VA anomalies at the CVJ.
      The incidence of VA anomalies at the CVJ was much higher in patients with Down
      syndrome than in those without Down syndrome. CONCLUSION: In planning surgery in
      patients with Down syndrome with symptomatic atlantoaxial subluxation and a
      congenital skeletal anomaly at the CVJ, we should consider the possible presence
      of VA anomalies. Preoperative 3DCTA allows us to precisely identify an anomalous
      VA and evaluate the possible risk of intraoperative VA injury in advance.

PMID- 18324394
TI  - Imaging findings in noncraniofacial childhood rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood. This
      paper is focuses on imaging for diagnosis, staging, and follow-up of
      noncraniofacial RMS.

PMID- 18324395
TI  - Structure and expression of MHC class Ib genes of the central M region in rat and
      mouse: M4, M5, and M6.
AB  - The M region at the telomeric end of the murine major histocompatibility complex
      (MHC) contains class I genes that are highly conserved in rat and mouse. We have
      sequenced a cosmid clone of the LEW rat strain (RT1 haplotype) containing three
      class I genes, RT1.M6-1, RT1.M4, and RT1.M5. The sequences of allelic genes of
      the BN strain (RT1n haplotype) were obtained either from cDNAs or genomic clones.
      For the coding parts of the genes few differences were found between the two RT1
      haplotypes. In LEW, however, only RT1.M5 and RT1.M6 have open reading frames;
      whereas in BN all three genes were intact. In line with the findings in BN,
      transcription was found for all three rat genes in several tissues from strain
      Sprague Dawley. Protein expression in transfectants could be demonstrated for
      RT1.M6-1 using the monoclonal antibody OX18. By sequencing of transcripts
      obtained by RT-PCR, a second, transcribed M6 gene, RT1.M6-2, was discovered,
      which maps next to RT1.M6-1 outside of the region covered by the cosmid. In
      addition, alternatively spliced forms for RT1.M5 and RT1.M6 were detected. Of the
      orthologous mouse genes, H2-M4, H2-M5, and H2-M6, only H2-M5 has an open reading
      frame. Other important differences between the corresponding parts of the M
      region of the two species are insertion of long LINE repeats, duplication of
      RT1.M6, and the inversion of RT1.M5 in the rat. This demonstrates substantial
      evolutionary dynamics in this region despite conservation of the class I gene
      sequences themselves.

PMID- 18324396
TI  - Subtractive hybridization and random arbitrarily primed PCR analyses of a
      benzoate-assimilating bacterium, Desulfotignum balticum.
AB  - Subtractive hybridization (SH) and random arbitrarily primed PCR (RAP-PCR) were
      used to detect genes involved in anaerobic benzoate degradation by Desulfotignum
      balticum. Through SH, we obtained 121 DNA sequences specific for D. balticum but
      not for D. phosphitoxidans (a non-benzoate-assimilating species). Furthermore,
      RAP-PCR analysis showed that a 651-bp DNA fragment, having 55% homology with the
      solute-binding protein of the ABC transporter system in Methanosarcina barkeri,
      was expressed when D. balticum was grown on benzoate, but not on pyruvate. By
      shotgun sequencing of the fosmid clone (38,071 bp) containing the DNA fragment,
      33 open reading frames (ORFs) and two incomplete ORFs were annotated, and several
      genes within this region corresponded to the DNA fragments obtained by SH. An
      11.3-kb gene cluster (ORF10-17) revealed through reverse transcription-PCR showed
      homology with the ABC transporter system and TonB-dependent receptors, both of
      which are presumably involved in the uptake of siderophore/heme/vitamin B(12),
      and was expressed in response to growth on benzoate.

PMID- 18324397
TI  - Bioreactor aeration conditions modulate growth and antigen expression during
      Erysipelothrix rhusiopathiae cultivation.
AB  - Erysipelothrix rhusiopathiae, the causative agent of swine erysipelas, was
      cultivated in a 5-L stirred and aerated bioreactor under different dissolved
      oxygen tensions (0%, 5%, and 30% of saturation) for evaluation of the influence
      of oxygen on cell growth as well as on the production of the main antigenic
      component of the vaccine against erysipelas, a 64-69 kDa protein (SpaA). The
      microorganism presented different growth profiles for different aeration
      conditions. However, at the end of the batch cultivations, similar cell
      concentrations were obtained under the studied conditions. In order to maximize
      biomass titers and antigen production, the microorganism was cultivated in fed
      batch operation mode under aerobic conditions. Under this condition, there was a
      fivefold increase in biomass production in comparison to the results attained in
      batch cultivations. To follow up antigen expression, samples collected during
      batch cultivations were concentrated and treated with choline for antigen
      extraction. Antigen expression was then assessed by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and by murine immunization tests. It was
      observed a direct influence of oxygen availability upon antigen expression, which
      is favored in the presence of oxygen. Analysis of the samples collected
      throughout the fed-batch process also revealed that antigen production is growth
      associated.

PMID- 18324398
TI  - Nephrogenic systemic fibrosis: chronic imaging findings and review of the medical
      literature.
AB  - Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder which has
      been strongly associated with exposure to gadolinium-based contrast media (GBCM)
      in the setting of renal insufficiency. Although this disorder primarily affects
      the skin, it can result in severe joint contractures, disabilities and even
      death. However, to date, there have been no published studies reporting chronic
      imaging findings of NSF. In this report we present three biopsy-proven cases of
      NSF with the associated chronic MRI, radiographic and bone scintigraphy findings.
      Two of the patients had been exposed to gadodiamide, and one had been exposed to
      gadopentetate dimeglumine prior to the onset of NSF. Two are newly reported
      cases. One patient's subacute imaging findings have previously been reported, but
      significant chronic images will now be presented. This patient became severely
      disabled from contractures and developed long bone smooth periosteal reaction,
      extensive intra-articular and periarticular calcifications, musculotendinous
      heterotopic ossification and ankylosis of several joints. One of the patients
      underwent renal transplantation 6 months after GBCM exposure, with near complete
      resolution of the skin fibrosis. The third patient had persistent MRI findings of
      skin thickening, with low T1 and high T2 signal intensity 5 years after exposure
      to gadodiamide. A review of the medical literature is provided, emphasizing the
      association of NSF with various GBCM. These cases broaden our understanding of
      the long-term imaging findings and complications of NSF and the stratified risk
      of NSF with various GBCM.

PMID- 18324399
TI  - Articular nodular fasciitis in the glenohumeral joint.
AB  - We describe a case of multiple intra-articular masses in the glenohumeral joint
      of a 15-year-old patient. The patient was treated with arthroscopic excision of
      the masses and synovectomy. Histological and immunohistochemical studies were
      consistent with those of a nodular fasciitis. Follow-up examination did not
      reveal recurrence at 6 months. In this article we report the first case of
      articular nodular fasciitis in the glenohumeral joint with unusual imaging
      findings.

PMID- 18324400
TI  - Immunotherapy of neuroblastoma by an Interleukin-21-secreting cell vaccine
      involves survivin as antigen.
AB  - AIM: IL-21 is the most recently identified member of the IL-2 cytokine family.
      Here we studied the therapeutic efficacy of IL-21-gene-modified cells (Neuro2a/IL
      21) in a syngeneic metastatic neuroblastoma (NB) model. MATERIALS AND METHODS:
      Neuro2a/IL-21 cells were tested as subcutaneous (sc) vaccine both in prophylactic
      and therapeutic settings. Depletion studies, cytotoxicity assay and
      immunohistochemical analyses were carried out to evaluate the mechanisms involved
      in tumor rejection. RESULTS: When injected sc in syngeneic A/J mice viable
      Neuro2a/IL-21 cells were rejected and induced resistance to a subsequent iv
      challenge with Neuro2a parental cells (Neuro2a/pc), suggesting the involvement of
      an immune response. More importantly, in mice bearing Neuro2a/pc micrometastases,
      a single sc injection of Neuro2a/IL-21 cells significantly increased the mean
      tumor-free survival of treated animals (43 vs. 22 days) and cured 14% of them.
      The administration of two or three doses of Neuro2a/IL-21 cell vaccine further
      increased the mean survival time to 54 and 75 days, and the cure rate to 27 and
      33%, respectively, whereas the use of unmodified Neuro2a or mock-transfected
      cells had no effect. In vivo cell subset depletion and a Winn-assay indicated the
      involvement of CD8 + CTLs. Immunohistochemical analysis indicated a reduction of
      CD31+ and VEGFR2+ microvessels in late metastases from therapeutically vaccinated
      mice. A role of survivin as antigen was suggested by in vitro assays using
      survivin-synthetic CTL-epitopes. CONCLUSIONS: Our present data indicate that IL
      21-secreting NB cells are effective as therapeutic vaccine in mice bearing
      metastatic NB, through a specific CTL response involving survivin as antigen, and
      suggest a potential interest for IL-21 in NB immuno-gene therapy.

PMID- 18324401
TI  - Stability comparison of anterior cruciate ligament between double- and single
      bundle reconstructions.
AB  - The purpose of this study was to evaluate the intra-operative stability during
      double-bundle anterior cruciate ligament (ACL) reconstructions (20 knees) using a
      navigation system and compare the results with those obtained from single-bundle
      reconstructions (20 knees). After registering the reference points during ACL
      reconstruction, antero-posterior and rotational stability tests with 30 degrees
      knee flexion using a navigation system were measured before and after
      reconstructions on both groups. The change of antero-posterior translation after
      and before reconstruction was 12.5 mm in the double-bundle group and 10.5 mm in
      the single-bundle group, showing significant inter-group difference (p=0.014,
      from 17.5 mm to 5.1 mm in the double-bundle and from 16.6 mm to 6.1 mm in the
      single-bundle group). The mean rotational stability of the double-bundle group
      also showed more significant improvement after reconstruction compared to that of
      the single-bundle group (9.8 degrees in the double- and 5.6 degrees in the single
      bundle groups, p<0.001). These findings suggest that a double-bundle ACL
      reconstruction restores greater knee stability with respect to the antero
      posterior and rotational stability than a single-bundle reconstruction.

PMID- 18324402
TI  - Delayed union of multifragmentary diaphyseal fractures after bridge-plate
      fixation.
AB  - Despite recent developments in fracture treatment, cases of non-union after long
      bone fractures are still encountered. This work aims at evaluating the active
      management of delayed union after the bridge-plate fixation of multifragmentary
      diaphyseal fractures by a limited surgical interference. Nineteen patients were
      included. All had revision surgery for delayed union of multifragmentary
      diaphyseal fractures after bridge-plate fixation. The period between primary and
      revision surgery was 12-20 weeks. Increasing stability was performed by adding
      more screws in all cases. Interfragmentary compression was performed in 16
      patients. Axial compression of the fracture was applied in two patients, while
      one patient had the plate exchanged for a longer one. Bone grafting was added in
      nine patients. Union was achieved in all patients 8-16 weeks after re-operation.
      This work is a message for timely surgical interference in delayed union after
      bridge-plate fixation by a limited surgical procedure, before complete failure of
      the fracture stabilisation or non-union.

PMID- 18324403
TI  - Vascularised iliac graft as a method of acetabular augmentation in subluxed hip
      in adolescents.
AB  - This article presents the clinical experience of patients with a dysplasic
      subluxated hip treated with the same procedure involving a vascularised graft of
      iliac crest by sartorius muscle. This study was performed in three different
      centres, in two different countries, and in 31 patients with 37 hips (9
      bilateral). All patients were clinically evaluated according to the Merle d
      Aubigne scale and radiological measuring of acetabular coverage, Sharp angle, and
      CE angle. Walking ability preoperatively was 4.87 and postoperatively 5.12, which
      was not statistically significant. Preoperative inclination acetabular angle was
      59.0 degrees +/- 6.23 and postoperatively 37.5 degrees +/- 6.08 (P < 0.00001).
      Preoperative CE angle was -2.03 degrees +/- 13.5 and postoperatively was 41.0
      degrees +/- 12.3 ( P < 0.00001). Index head acetabulum had a preoperative
      coverage of 48.3% +/- 13.0 and postoperatively 100.8% +/- 19.5. The head
      sphericity did not show any statistically significant difference in relation to
      the results. The results obtained were satisfactory from every point of view,
      making this the procedure of choice in the armamentarium to delay the need for a
      total joint as treatment of early osteoarthritis in young adults.

PMID- 18324404
TI  - Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis
      outlasts inflammatory process resolution.
AB  - AIM: To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced
      intestinal mucositis. MATERIALS AND METHODS: Wistar rats received 5-FU (150 mg
      kg(-1), i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of
      duodenum, jejunum and ileum were removed for assessment of epithelial damage,
      apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to
      study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment,
      gastric emptying in vivo was measured by scintilographic method, and stomach or
      duodenal smooth muscle contractions induced by CCh were evaluated in vitro.
      RESULTS: On the third day of treatment, 5-FU induced a significant villi
      shortening, an increase in crypt depth and intestinal MPO activity and a decrease
      in villus/crypt ratio and GSH concentration. On the first day after 5-FU there
      was an increase in the apoptosis index and a decrease in the mitosis index in all
      intestinal segments. After the 15th day of 5-FU treatment, a complete reversion
      of all these parameters was observed. There was a delay in gastric emptying in
      vivo and a significant increase in gastric fundus and duodenum smooth muscle
      contraction, after both the 3rd and 15th day. CONCLUSION: 5-FU-induced
      gastrointestinal dysmotility outlasts intestinal mucositis.

PMID- 18324405
TI  - Separate visualization of endolymphatic space, perilymphatic space and bone by a
      single pulse sequence; 3D-inversion recovery imaging utilizing real
      reconstruction after intratympanic Gd-DTPA administration at 3 Tesla.
AB  - Twenty-four hours after intratympanic administration of gadolinium contrast
      material (Gd), the Gd was distributed mainly in the perilymphatic space. Three
      dimensional FLAIR can differentiate endolymphatic space from perilymphatic space,
      but not from surrounding bone. The purpose of this study was to evaluate whether
      3D inversion-recovery turbo spin echo (3D-IR TSE) with real reconstruction could
      separate the signals of perilymphatic space (positive value), endolymphatic space
      (negative value) and bone (near zero) by setting the inversion time between the
      null point of Gd-containing perilymph fluid and that of the endolymph fluid
      without Gd. Thirteen patients with clinically suspected endolymphatic hydrops
      underwent intratympanic Gd injection and were scanned at 3 T. A 3D FLAIR and 3D
      IR TSE with real reconstruction were obtained. In all patients, low signal of
      endolymphatic space in the labyrinth on 3D FLAIR was observed in the anatomically
      appropriate position, and it showed negative signal on 3D-IR TSE. The low signal
      area of surrounding bone on 3D FLAIR showed near zero signal on 3D-IR TSE. Gd
      containing perilymphatic space showed high signal on 3D-IR TSE. In conclusion, by
      optimizing the inversion time, endolymphatic space, perilymphatic space and
      surrounding bone can be separately visualized on a single image using a 3D-IR TSE
      with real reconstruction.

PMID- 18324406
TI  - Diffusion-weighted imaging in patients with progressive multifocal
      leukoencephalopathy.
AB  - Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating
      disease of the central nervous system due to JC polyoma virus infection of
      oligodendrocytes. PML develops in patients with impaired T-cell function as
      occurs in HIV, malignancy or immunosuppressive drugs users. Until now no imaging
      methods have been reported to correlate with clinical status. Diffusion-weighted
      imaging (DWI) is a robust MRI tool in investigating white matter architecture and
      diseases. The aim of our work was to assess diffusion abnormalities in focal
      white matter lesions in patients with PML and to correlate the lesion load
      measured with conventional MRI and DWI to clinical variables. We evaluated eight
      patients with a biopsy or laboratory-supported diagnosis of PML. All patients
      underwent MRI including conventional sequences (fluid attenuated inversion
      recovery-FLAIR) and DWI. Mean diffusivity (MD) maps were used to quantify
      diffusion on white matter lesions. Global lesion load was calculated by manually
      tracing lesions on FLAIR images, while total, central core and peripheral lesion
      loads were calculated by manually tracing lesions on DWI images. Lesion load
      obtained with the conventional or DWI-based methods were correlated with clinical
      variables such as disease duration, disease severity and survival. White matter
      focal lesions are characterized by a central core with low signal on DWI images
      and high MD (1.853 x 10(-3) mm2/s), surrounded by a rim of high signal intensity
      on DWI and lower MD (1.1 x 10(-3) mm2/s). The MD value of normal-appearing white
      matter is higher although not statistically significant (0.783 x 10(-3) mm2/s)
      with respect to control subjects (0.750 x 10(-3) mm2/s). Inter-rater correlations
      of global lesion load between FLAIR (3.96%) and DWI (3.43%) was excellent
      (ICC=0.87). Global lesion load on FLAIR and DWI correlates with disease duration
      and severity (respectively, p=0.037, p=0.0272 with Karnofsky scale and p=0.0338
      with EDSS on FLAIR images; p=0.043, p=0.0296 with Karnofsky scale and p=0.0365
      with EDSS on DW images). Central core lesion load on DWI correlates with disease
      duration and severity (respectively p=0.043, p=0.0103 with Karnofsky scale and
      p=0.0112 with EDSS), while peripheral lesion load does not correlate with any
      clinical variable. The global lesion load in PML correlates with disease duration
      and severity. DWI images, which can distinguish within lesions a central core
      from a peripheral rim, reveal that a larger central core component correlates to
      a worsened clinical status and longer disease duration. On the other hand the
      peripheral rim lesion load visualized on DWI images does not correlate with
      clinical variables and does not achieve obtaining further prognostic information
      with respect to conventional imaging.

PMID- 18324407
TI  - Initial clinical experience with full-length metal ureteral stents for
      obstructive ureteral stenosis.
AB  - OBJECTIVES: Long-term ureteral stenting is used to ensure urinary drainage if a
      reconstructive approach or a release of an extrinsic obstruction is not possible.
      In this contribution, a long-term experience with a new full-length, metal
      indwelling stent is presented. METHODS: Fourteen patients with ureteral
      obstruction received full metal indwelling stents in 18 collecting systems
      (benign disease in 5 and malignant disease in 13). Stent placement was performed
      cystoscopically under fluoroscopic guidance. Follow-up was done every 3 months
      with ultrasonographic examination, creatinine levels, and a visual analog pain
      score. RESULTS: Eight stents were removed, whereas eight are still in situ. One
      patient without stent-related problems died because of progressive rectal cancer
      9 months after bilateral stent insertion. Mean stent duration (8 stents still in
      situ) is 8.6 months, whereas mean stent duration for benign and malignant disease
      is 11.8 (median 13) and 7.3 (median 6) months, respectively (p<0.05). All removed
      stents were extracted endoscopically without any problems and had no incrustation
      except two. Neither migration nor mechanical damage was observed. CONCLUSION:
      This novel stent is easy to insert and remove. It is an option for patients in
      which a surgical reconstruction of the obstructed ureter is not possible. Stents
      have been developed further and are now available in various lengths. This might
      result in a reduction of problems associated with inadequate stent length and
      should increase patient comfort and stent durability.

PMID- 18324408
TI  - Role of galeal-pericranial flap in reducing postoperative CSF leak in patients
      with intracranial endoscopic procedures.
AB  - OBJECTIVE: The authors describe a simple technique to reduce the incidence of
      cerebrospinal fluid (CSF) leak following endoscopic third ventriculostomy and
      other neuroendoscopic procedures. METHODS: After the scalp incision, the galea
      and pericranium are reflected in a single layer after the scalp incision which is
      then closed in a watertight fashion after the procedure is completed. The
      securely closed flap prevents minor CSF leaks which would have otherwise required
      intermittent CSF drainage procedures. CONCLUSION: This simple procedural
      modification is effective in children with thin cortical mantle and large
      ventricles who are otherwise highly susceptible for CSF leak in the postoperative
      period.

PMID- 18324409
TI  - Interferon-beta therapy for malignant melanoma: the dose is crucial for
      inhibition of proliferation and induction of apoptosis of melanoma cells.
AB  - We investigated the anti-tumor effect of human interferon-beta (HuIFN-beta)
      against malignant melanoma. In vitro study revealed that HuIFN-beta not only
      inhibited proliferation of melanoma cells (seven cell lines: MM-AN, MM-BP, MM-LH,
      MM-RU, PM-WK, RPM-EP, RPM-MC) but also induced apoptosis in a dose dependent
      fashion, though the sensitivity to HuIFN-beta was different among cell lines. In
      addition, we administered HuIFN-beta into cutaneous metastatic lesions of
      melanoma and evaluated clinical and histopathological effects. Although the size
      of the metastatic cutaneous lesion did not change by the intralesional injection
      of HuIFN-beta, histopathological examination revealed apoptotic changes of
      melanoma cells along with dense lymphohistiocytic infiltration. The present study
      confirmed direct and indirect inhibitory effects of HuIFN-beta on human melanoma
      cells and suggests that local higher concentration of HuIFN-beta is needed to
      eradicate melanoma lesions.

PMID- 18324410
TI  - The management of otitis externa: a randomised controlled trial of a glycerol and
      icthammol ribbon gauze versus topical antibiotic and steroid drops.
AB  - We compared the use of glycerol and icthammol (G&I) ribbon gauze versus topical
      antibiotic and steroid drops in the management of otitis externa. Patients
      presenting with acute otitis externa were systematically recruited from
      attendance in the ENT emergency clinic. Exclusion criteria were age <18 years,
      diabetic patients, and those who had been previously treated for otitis externa
      by the department within the last month. A total of 43 patients were recruited
      with 48 infected ears, the mean patient age was 47 years, (range 18-80 years).
      Patients were randomised to either insertion of a G&I ribbon gauze or topical ear
      drops by means of a ballot with no stratification. All patients were reviewed 5
      days later. Patients were asked to comment on their pain using the ten point
      visual analogue pain score. Oedema of the canal wall, presence of debris and
      visibility of the tympanic membrane were graded on microscopy. Patient
      satisfaction and return to work were assessed. There was a statistically
      significant decrease in the pain score between each visit for the entire group of
      patients and decrease in canal wall swelling (P < 0.001). There was no
      significant difference between drops and ribbon gauze in terms of pain relief,
      canal wall oedema, or aural discharge. Following microbiological analysis, 27.8%
      of bacteria were resistant to neomycin. The cost of treatment with G&I is less
      than a third of that for topical antibiotic-steroid drops and requires less
      patient compliance. Patient concerns with the ribbon gauze included its cosmetic
      appearance and loss of hearing and with drops included frequency of application.
      We recommend the use of G&I ribbon gauze as first-line treatment, particularly
      for those who have had allergies to carriers of drops, those that are poorly
      compliant or with poor manual dexterity, for example patients with rheumatic
      hands.

PMID- 18324411
TI  - The non-gastric H,K-ATPase as a tool to study the ouabain-binding site in Na,K
      ATPase.
AB  - Based on studies with chimeras between (non-)gastric H,K-ATPase and Na,K-ATPase,
      a model for the ouabain binding site has recently been presented (Qiu et al.
      J.Biol.Chem. 280 (2005) 32349). In this model, hydrogen bonds between specific
      amino acid residues of Na,K-ATPase and hydroxyl groups of ouabain play a crucial
      role. In the present study, a series of ouabain analogues were tested on
      baculovirus-expressed Na,K-ATPase and an ouabain-sensitive mutant of non-gastric
      H,K-ATPase (D312E/ S319G/ A778P/ I795L/ F802C). For each analogue, the results
      obtained by measuring ATPase inhibition and [(3)H]ouabain replacement agreed
      rather well. In Na,K-ATPase, strophanthidin had a 7-10 times higher and digoxin a
      4-12 times lower affinity than ouabain. The results of the non-gastric H,K-ATPase
      mutant were rather similar to that of Na,K-ATPase with exception of dihydro
      ouabain that showed a much lower affinity with the non-gastric H,K-ATPase mutant.
      Docking studies showed that all analogues bind to the same pocket in Na,K-ATPase.
      However, the amino acids to which hydrogen bonds were formed differed and
      depended on the availability of hydroxyl or keto groups in the ouabain analogues.

PMID- 18324412
TI  - Similar mechanisms might be triggered by alternative external stimuli that induce
      dormancy release in grape buds.
AB  - The detection of genes having similar expression profiles following the
      application of different stimuli that trigger bud break may constitute potent
      tools for the identification of pathways with a central role in dormancy release.
      We compared the effects of heat shock (HS) and hydrogen cyanamide (HC) and
      demonstrated that HS leads to earlier and higher bud-break levels. Changes in
      transcript levels of catalase, alcohol dehydrogenase and pyruvate decarboxylase
      were induced following both treatments. However, timing and extent of changes in
      transcript level differed. Changes occurred earlier in HS-treated buds and were
      more intense in HC-treated buds. The changes in transcript levels after both
      treatments were temporary. The rapid and short-lasting changes in gene expression
      following HS treatment correlated with the faster and higher level of bud-break
      that this treatment exerted. This correlation may propose that the reported
      molecular events are mechanistically involved in dormancy release. To test the
      hypothesis that temporary oxidative stress is part of the mechanism inducing
      dormancy release, we analyzed the effect of HS and HC treatments on the
      expression of ascorbate peroxidase, glutathione reductase, thioredoxin h,
      glutathione S-transferase and sucrose synthase genes and found that they were
      induced by both treatments in a similar pattern. Taken together, these findings
      propose that similar cellular processes might be triggered by different stimuli
      that lead to dormancy release, and are consistent with the hypothesis that
      temporary oxidative stress and respiratory stress might be part of the mechanism
      that leads to bud break.

PMID- 18324413
TI  - Post-harvest regulated gene expression and splicing efficiency in storage roots
      of sugar beet (Beta vulgaris L.).
AB  - Sixteen post-harvest upregulated genes from sugar beet comprising five novel
      sequences were isolated by subtractive cloning. Transcription profiles covering a
      period of up to 49 days after harvest under controlled storage conditions and in
      field clamps are reported. Post-harvest induced genes are involved in wound
      response, pathogen defense, dehydration stress, and detoxification of reactive
      oxygen species. An early induction of a cationic peroxidase indicates a response
      to post-harvest damage. Wound response reactions may also involve genes required
      for cell division such as a regulator of chromatin condensation and a precursor
      of the growth stimulating peptide phytohormone phytosulfokine-alpha.
      Surprisingly, also three putative non-protein coding genes were isolated. Two of
      these genes show intron specific and storage temperature dependent splicing of a
      precursor mRNA. The temperature dependent splicing of an intron containing sugar
      beet mRNA is also maintained in transgenic Arabidopsis thaliana. The storage
      induced genes are integrated into a model that proposes the response to several
      post-harvest stress conditions. Temperature regulated splicing may be a mechanism
      to sense seasonal temperature changes.

PMID- 18324414
TI  - Temporal dissociation between category-based and item-based processes in
      rejecting distractors.
AB  - Presenting a target-like distractor in an RSVP task deteriorates the detection of
      a trailing target, because the visual system has difficulties in rejecting the
      erroneously accepted distractor. We investigated whether the rejection process is
      influenced by observers' knowledge regarding possible distractors. Observers
      identified a letter (target) embedded in a stream of line patterns, rejecting a
      preceding distractor (digit). We informed the observers about either the category
      of distractors ("digit") or the identity of the distractor (e.g., "5"). The
      distractors with certain distractor-target lags increased identification errors,
      indicating that the distractor rejection process temporarily interfered with the
      target identification. When the observers knew the distractor identity, the
      rejection process started later than when they knew only the distractor category.
      These results suggest that the rejection process may operate at either the
      category or the individual-item level; however, the setting of the rejection
      level is not under the observers' control.

PMID- 18324415
TI  - Conditional gene expression systems to study herpesvirus biology in vivo.
AB  - Cytomegalovirus (CMV), a prototypic beta-herpesvirus, is an important human
      pathogen causing protean clinical manifestations in immature and
      immunocompromised patients. Mechanisms of infection can be studied in a mouse
      model. Mouse cytomegalovirus (MCMV) resembles in pathogenesis its human
      counterpart in many ways. Although MCMV infection is studied extensively on the
      level of organs, the contribution of specific cell types to viral replication in
      vivo is still elusive. Here we describe our approach based on the the Cre/loxP
      system to investigate MCMV infection at the level of cell types in vivo. Using
      bacterial artificial chromosome (BAC)-technology, we created an MCMV virus
      containing an enhanced green fluorescent protein (egfp) reporter-gene which is
      not expressed due to a 'Stop' cassette flanked by two loxP-sites between promoter
      and coding sequence. Infection of cre-transgenic mice with this reporter virus
      results in the deletion of the 'Stop' cassette and expression of EGFP in a cell
      type-specific manner. Using this conditional gene expression system we are able
      to quantify viral productivity in specific cell types and to determine their
      contribution to viral dissemination in vivo. Furthermore, the deletion of viral
      genes can be used to screen for cell type-specificity of viral gene functions.
      Hence, conditional MCMV mutants allow the study of herpesvirus biology on the
      level of cell types in vivo.

PMID- 18324416
TI  - Genomic DNA sequence comparison between two inbred soybean cyst nematode biotypes
      facilitated by massively parallel 454 micro-bead sequencing.
AB  - Heterodera glycines, the soybean cyst nematode (SCN), is a damaging agricultural
      pest that could be effectively managed if critical phenotypes, such as virulence
      and host range could be understood. While SCN is amenable to genetic analysis,
      lack of DNA sequence data prevents the use of such methods to study this
      pathogen. Fortunately, new methods of DNA sequencing that produced large amounts
      of data and permit whole genome comparative analyses have become available. In
      this study, 400 million bases of genomic DNA sequence were collected from two
      inbred biotypes of SCN using 454 micro-bead DNA sequencing. Comparisons to a BAC,
      sequenced by Sanger sequencing, showed that the micro-bead sequences could
      identify low and high copy number regions within the BAC. Potential single
      nucleotide polymorphisms (SNPs) between the two SCN biotypes were identified by
      comparing the two sets of sequences. Selected resequencing revealed that up to
      84% of the SNPs were correct. We conclude that the quality of the micro-bead
      sequence data was sufficient for de novo SNP identification and should be
      applicable to organisms with similar genome sizes and complexities. The SNPs
      identified will be an important starting point in associating phenotypes with
      specific regions of the SCN genome.

PMID- 18324417
TI  - Programmed cell death suppression in transformed plant tissue by tomato cDNAs
      identified from an Agrobacterium rhizogenes-based functional screen.
AB  - The genetic regulation of programmed cell death (PCD) is well characterized in
      animal systems, but largely unresolved in plants. This research was designed to
      identify plant genes that can suppress PCD triggered in plants by Fumonisin B1
      (FB1). Agrobacterium rhizogenes was used to transform individual members of a
      cDNA library into tomato roots, which were then screened for resistance to FB1.
      Cellular changes elicited during FB1-induced PCD include chromatin condensation,
      fragmentation into pycnotic DNA bodies, TUNEL positive reactions, ROS
      accumulation, and eventual loss of membrane integrity. Several cDNA library
      members collectively overexpressed in a transformed root population revealed PCD
      suppressive action and were recovered by PCR. One of the FB1 suppressive genes
      was homologous to metallothionein, and shared sequence homology to the animal
      ortholog reported to suppress PCD through interference with formation or activity
      of reactive oxygen species (ROS). The metallothionein recovered in this screen
      suppressed ROS accumulation in FB1-treated roots and prevented symptoms of PCD.
      Anti-PCD genes recovered by this screen represent potential sources of resistance
      to PCD-dependent plant diseases, while the screen should be useful to identify
      genes capable of suppressing PCD triggered by other effectors, including those
      expressed by root pathogens during infection.

PMID- 18324418
TI  - Sensitive immunoassay of human chorionic gonadotrophin based on multi-walled
      carbon nanotube-chitosan matrix.
AB  - A novel amperometric immunosensor for human chorionic gonadotropin (HCG) assay
      has been fabricated through incorporating toluidine blue (TB) and hemoglobin (Hb)
      on the multiwall carbon nanotube (MWNT)-chitosan (CS) modified glassy carbon
      electrode, followed by electrostatic adsorption of a conducting gold
      nanoparticles (nanogold) film as sensing interface. The MWNT-CS matrix provided a
      congenial microenvironment for the immobilization of biomolecules and promoted
      the electron transfer to enhance the sensitivity of the immunosensor. Due to the
      strong electrocatalytic properties of Hb and MWNT toward H(2)O(2), the Hb and
      MWNT significantly amplified the current signal of the antigen-antibody reaction.
      The immobilized toluidine blue as an electron transfer mediator exhibited
      excellent electrochemical redox property. After the immunosensor was incubated
      with HCG solution, the access of activity center of the Hb to toluidine blue was
      partly inhibited, which leaded to a linear decrease in the catalytic efficiency
      of the Hb to the oxidation of immobilized toluidine blue by H(2)O(2) over HCG
      concentration ranges from 0.8 to 500 mIU/mL. Under optimal condition, the
      detection limit for the HCG immunoassay was 0.3 mIU/mL estimated at a signal-to
      noise ratio of 3. Moreover, the proposed immunosensor displayed a satisfactory
      stability and reproducibility.

PMID- 18324419
TI  - High serological response to pneumococcal vaccine in nephrotic children at
      disease onset on high-dose prednisone.
AB  - Our objective was to demonstrate that nephrotic children at disease onset and
      under high-dose prednisone respond to vaccination with 23-valent pneumococcal
      vaccine (PV). We compared the serological response after PV in 30 children with
      nephrotic syndrome, directly after initiation of prednisone therapy (60 mg/m2
      body surface area) at disease onset (group 1), with the response in 13 patients
      who received the vaccine while in remission (group 2). Safety was studied,
      comparing disease course in group 1 with those in patients who did not receive
      any PV (group 3). In group 1, 23-valent PV antibody (Ab) levels increased tenfold
      after 1 month and remained increased after 1 year (P < 0.01). Ab response in the
      short term and in the long term was not different from that of patients in group
      2. Serum albumin, age, or immunosuppressive drugs did not influence Ab response.
      Disease courses in groups 1 and 3 were not different. In conclusion, nephrotic
      children on high-dose glucocorticoid therapy respond to a 23-valent anti-PV.
      Children with steroid dependent/resistant forms acquire high Ab levels, even if
      early relapses delay the tapering of steroids or if immunosuppressive agents are
      introduced. Patients who relapse during the tapering of steroids already have
      increased anti-pneumococcal Ab at the time of relapse.

PMID- 18324420
TI  - Urine erythrocyte morphology in patients with microscopic haematuria caused by a
      glomerulopathy.
AB  - The evaluation of urinary erythrocyte morphology (UEM) has been proposed for
      patients with isolated microscopic haematuria (IMH) to early orientate the
      diagnosis towards a glomerular or a nonglomerular disease. However, to date, the
      role of this test in patients with IMH has very rarely been investigated. Sixteen
      patients (ten children, six adults) with persistent IMH classified as glomerular
      on the basis of repeated UEM evaluations (55 urine samples, two to eight per
      patient) were submitted to renal biopsy. This showed a glomerular disease in
      14/16 patients (87.5%) (nine thin basement membrane disease; three Alport
      syndrome; two other), whereas in two patients, no abnormalities were found. Of
      four microscopic criteria investigated to define a IMH as glomerular, >80%
      dysmorphic erythrocytes were not found in any sample, >or=40% dysmorphic
      erythrocytes alone were seen in seven samples (12.7%), >or=5% acanthocytes alone
      in 15 samples (27.3%) and erythrocytic casts in six samples (10.9%). There was
      >or=40% dysmorphic erythrocytes associated with >or=5% acanthocytes in 25 samples
      (45.5%). Sensitivity and positive predictive values in diagnosing a glomerular
      haematuria were 59.2% and 90.6%, respectively, for >or=40% dysmorphic
      erythrocytes, 69.4% and 85% for >or=5% acanthocytes/G1 cells and 12.2% and 100%
      for erythrocytic casts. Our findings demonstrate that the evaluation of UEM is
      useful to identify patients with an IMH of glomerular origin.

PMID- 18324421
TI  - Long-term follow-up after cyclophosphamide and cyclosporine-A therapy in steroid
      dependent and -resistant nephrotic syndrome.
AB  - A retrospective study was made on 37 children with idiopathic nephrotic syndrome
      (INS). At the beginning, all patients were steroid sensitive but received more
      than one steroid course (median 4). Following several relapses, they became
      steroid dependent or steroid resistant. Group 1 consisted of 22 children [3 focal
      segmental glomerulosclerosis (FSGS), 19 minimal-change NS (MCNS)] who received
      cyclophosphamide (CP) orally for 2.5 +/- 0.5 months. Group 2 consisted of 15
      children (7 FSGS, 8 MCNS) who received cyclosporine-A (CSA) for 28 +/- 15 months.
      The level of proteinuria decreased significantly and remained low during the
      follow-up. The relapse-free period was significantly longer in the CP group (CP
      30 +/- 21.5; CSA 26.2 +/- 18 months, p < 0.001). The relapse rate decreased
      significantly in both groups and remained in this lower level during the follow
      up (from 3.4 +/- 2.8 to 0.1 +/- 0.2/year in group 1, and from 3.7 +/- 3.1 to 0.6
      +/- 0.8/year in group 2). At the end of the 5-year follow-up, 20/22 patients
      (90.9%) and 10/15 patients (66.6%) were in remission in groups 1 and 2
      respectively, with or without treatment (p < 0.05). In the long term, both CP and
      CSA is effective second-line therapy following steroid monotherapy in INS
      patients, but the relapse rate was lower and the relapse free period was
      significantly longer in the CP-treated group.

PMID- 18324422
TI  - Metabolic risk factors in children with kidney stone disease.
AB  - The evaluation of metabolic risk factor in children with renal stone disease is
      the basis of medical treatment aimed at preventing recurrent stone events and the
      growth of preexisting calculi. In this retrospective study, we evaluated the
      metabolic risk factors and clinical and family histories of 90 children with
      kidney stone disease who had been referred to our institution and subjected to
      clinical tests using a standardized protocol. The mean age of our pediatric
      patients was 10.7 years, and the male:female ratio was 1.14:1.0. Biochemical
      abnormalities were found in 84.4% of all cases. A single urine metabolic risk
      factor was present in 52.2% (n = 47) of the patients, and multiple risk factors
      were present in the remaining 31.1% (n = 28). Idiopathic hypercalciuria (alone or
      in combination) and hypocitraturia (alone or in combination) were the most
      frequent risk factors identified in 40 and 37.8% of these patients, respectively.
      Renal colic or unspecified abdominal pain were the most frequent forms of
      presentation (76.9%), with 97.5% of stones located in the upper urinary tract. In
      most patients, stone disease was confirmed by renal ultrasonography (77%). A
      positive family history in first-degree and second-degree relatives was found in
      46.2 and 32.5% of the cases, respectively. We conclude that specific urine
      metabolic risk factors are found in most children with kidney stones and that
      hypocitraturia is as frequent as hypercalciuria. Very often there is a positive
      family history of renal stone disease in first- and second-degree relatives.

PMID- 18324423
TI  - What is new in uremic toxicity?
AB  - Uremic syndrome results from a malfunctioning of various organ systems due to the
      retention of compounds which, under normal conditions, would be excreted into the
      urine and/or metabolized by the kidneys. If these compounds are biologically
      active, they are called uremic toxins. One of the more important toxic effects of
      such compounds is cardio-vascular damage. A convenient classification based on
      the physico-chemical characteristics affecting the removal of such compounds by
      dialysis is: (1) small water-soluble compounds; (2) protein-bound compounds; (3)
      the larger "middle molecules". Recent developments include the identification of
      several newly detected compounds linked to toxicity or the identification of as
      yet unidentified toxic effects of known compounds: the dinucleotide
      polyphosphates, structural variants of angiotensin II, interleukin-18, p
      cresylsulfate and the guanidines. Toxic effects seem to be typically exerted by
      molecules which are "difficult to remove by dialysis". Therefore, dialysis
      strategies have been adapted by applying membranes with larger pore size (high
      flux membranes) and/or convection (on-line hemodiafiltration). The results of
      recent studies suggest that these strategies have better outcomes, thereby
      clinically corroborating the importance attributed in bench studies to these
      "difficult to remove" molecules.

PMID- 18324424
TI  - Mesangial hypercellularity in children: presenting features and outcomes.
AB  - Mesangial hypercellularity (MH), in the absence of sclerosis or immune
      deposition, was a common finding on renal biopsy in our center. We studied 66
      children with predominant MH. Among all patients older than 2.7 years, blood
      pressure (BP) percentile and glomerular filtration rate (GFR) remained stable.
      Serum albumin (Alb) trended higher (3.0+/-0.2 start vs. 3.4+/-0.2 end g/dl,
      p=0.06) and urine protein/creatinine lower (4.2+/-0.9 start vs. 2.3+/-0.9 end
      mg/mg, p=0.18) at the end of the study period. The proportion with stage 1 CKD
      remained constant: 94% start vs. 92% end. At end, Alb was lower in patients
      referred for nephrotic syndrome (NS): 4.4+/-0.3 hematuria vs. 4.2+/-0.2
      proteinuria vs. 2.8+/-0.3 NS g/dl, p<0.05 vs. both. Alb was lower (p=0.03) and
      urine protein/creatinine trended higher in patients with diffuse foot-process
      fusion (FPF). Twenty-five percent of patients with focal FPF developed NS, all
      had relapses, and 63% were steroid sensitive (SS). All but one with diffuse FPF
      presented with NS; 86% had relapses (mean 1 year) and 63% were SS. GFR trended
      higher at the end in those with matrix thickening (mat) (119.6+/-4.7 no mat vs.
      129.1+/-2.6 mat ml/min per 1.73 m2, p=0.1). Those without mat were less SS (59%
      no mat vs. 80% mat) and were more likely to require alkylating agents (Alk) for
      NS. Among those with positive immunofluorescence (IF), 82% had immunoglobulin M
      (IgM) alone; those with positive IF were more SS and needed Alk for NS. MH
      predicts a favorable prognosis. FPF predicts NS and multiple relapses.

PMID- 18324426
TI  - Degenerative lumbar spinal stenosis: correlation with Oswestry Disability Index
      and MR imaging.
AB  - Because neither the degree of constriction of the spinal canal considered to be
      symptomatic for lumbar spinal stenosis nor the relationship between the clinical
      appearance and the degree of a radiologically verified constriction is clear, a
      correlation of patient's disability level and radiographic constriction of the
      lumbar spinal canal is of interest. The aim of this study was to establish a
      relationship between the degree of radiologically established anatomical stenosis
      and the severity of self-assessed Oswestry Disability Index in patients
      undergoing surgery for degenerative lumbar spinal stenosis. Sixty-three
      consecutive patients with degenerative lumbar spinal stenosis who were scheduled
      for elective surgery were enrolled in the study. All patients underwent
      preoperative magnetic resonance imaging and completed a self-assessment Oswestry
      Disability Index questionnaire. Quantitative image evaluation for lumbar spinal
      stenosis included the dural sac cross-sectional area, and qualitative evaluation
      of the lateral recess and foraminal stenosis were also performed. Every patient
      subsequently answered the national translation of the Oswestry Disability Index
      questionnaire and the percentage disability was calculated. Statistical analysis
      of the data was performed to seek a relationship between radiological stenosis
      and percentage disability recorded by the Oswestry Disability Index. Upon
      radiological assessment, 27 of the 63 patients evaluated had severe and 33
      patients had moderate central dural sac stenosis; 11 had grade 3 and 27 had grade
      2 nerve root compromise in the lateral recess; 22 had grade 3 and 37 had grade 2
      foraminal stenosis. On the basis of the percentage disability score, of the 63
      patients, 10 patients demonstrated mild disability, 13 patients moderate
      disability, 25 patients severe disability, 12 patients were crippled and three
      patients were bedridden. Radiologically, eight patients with severe central
      stenosis and nine patients with moderate lateral stenosis demonstrated only
      minimal disability on percentage Oswestry Disability Index scores. Statistical
      evaluation of central and lateral radiological stenosis versus Oswestry
      Disability Index percentage scores showed no significant correlation. In
      conclusion, lumbar spinal stenosis remains a clinico-radiological syndrome, and
      both the clinical picture and the magnetic resonance imaging findings are
      important when evaluating and discussing surgery with patients having this
      diagnosis. MR imaging has to be used to determine the levels to be decompressed.

PMID- 18324425
TI  - Slowing chronic kidney disease progression: results of prospective clinical
      trials in adults.
AB  - Chronic kidney disease is generally thought to be a progressive disorder
      regardless of etiology. Over the past 15 years, investigations into the
      mechanisms of disease progression and treatment designed to slow or halt disease
      progression have been conducted, largely in the adult kidney disease population.
      Intervention trials have demonstrated that lowering blood pressure in
      hypertensive patients and administration of drugs that block the renin
      angiotensin aldosterone system are effective at slowing kidney disease
      progression, including diabetes, hypertension, and various glomerular diseases.
      In addition, novel strategies including anemia therapy with erythropoietin
      stimulating agents have been conducted to determine whether treatment of this
      common complication of kidney disease can stabilize kidney function. Whereas
      substantial success has been achieved in more common forms of adult kidney
      disease such as diabetes and hypertension, slowing progression of some immune
      mediated glomerular disease such as lupus nephritis and immunoglobulin A (IgA)
      nephropathy remain a great challenge. Moreover, there is no proven strategy,
      including multifactorial interventions, that clearly halts progressive chronic
      kidney disease that has been studied prospectively in a large-scale, long-term
      trial. The purpose of this review is to discuss these trials, as they form the
      underpinnings for current clinical practice guidelines in adults with chronic
      kidney disease.

PMID- 18324427
TI  - Efficacy and safety of caspofungin therapy in elderly patients with proven or
      suspected invasive fungal infections.
AB  - Invasive fungal infections (IFIs) are serious complications in elderly adults.
      Caspofungin may provide a useful therapeutic option for elderly patients with or
      at high risk for IFIs. We retrospectively compared efficacy and safety outcomes
      in elderly (> or = 65 years of age) and non-elderly patients in three clinical
      trials of caspofungin: a double-blind, randomized trial versus amphotericin B for
      documented invasive candidiasis (IC); an open-label, non-comparative study of
      definite or probable invasive aspergillosis (IA); and a double-blind, randomized
      trial versus liposomal amphotericin B as empirical therapy (ET) in febrile
      neutropenic patients. A total of 159 elderly patients with a median age of 71
      years (range, 65-84) received caspofungin in these studies. The median duration
      of caspofungin therapy was 12 days for IC and ET, and 28 days for IA. Point
      estimates for the favorable response rates to caspofungin were numerically higher
      in elderly versus non-elderly patients with IC (83% vs. 68%) or IA (64% vs. 44%)
      and were similar in patients receiving ET (36% vs. 34%). Adverse events related
      to caspofungin occurred in generally similar proportions of elderly versus non
      elderly patients with IC (clinical, 33% vs. 27%; laboratory, 17% vs. 29%), with
      IA (clinical, 7% vs. 13%; laboratory, 13% vs. 14%), or receiving ET (clinical,
      47% vs. 47%; laboratory, 24% vs. 22%). Nephrotoxicity and infusion-related
      toxicity developed in comparable proportions of elderly and non-elderly
      caspofungin recipients in all three studies. In this post-hoc analysis,
      caspofungin appeared to be as efficacious and well tolerated in elderly patients
      as in non-elderly patients.

PMID- 18324428
TI  - Pyrosequencing analysis of the gyrB gene to differentiate bacteria responsible
      for diarrheal diseases.
AB  - Pathogens causing acute diarrhea include a large variety of species from
      Enterobacteriaceae and Vibrionaceae. A method based on pyrosequencing was used
      here to differentiate bacteria commonly associated with diarrhea in China; the
      method is targeted to a partial amplicon of the gyrB gene, which encodes the B
      subunit of DNA gyrase. Twenty-eight specific polymorphic positions were
      identified from sequence alignment of a large sequence dataset and targeted using
      17 sequencing primers. Of 95 isolates tested, belonging to 13 species within 7
      genera, most could be identified to the species level; O157 type could be
      differentiated from other E. coli types; Salmonella enterica subsp. enterica
      could be identified at the serotype level; the genus Shigella, except for S.
      boydii and S. dysenteriae, could also be identified. All these isolates were also
      subjected to conventional sequencing of a relatively long ( approximately1.2 kb)
      region of gyrB DNA; these results confirmed those with pyrosequencing. Twenty-two
      fecal samples were surveyed, the results of which were concordant with culture
      based bacterial identification, and the pathogen detection limit with simulated
      stool specimens was 10(4) CFU/ml. DNA from different pathogens was also mixed to
      simulate a case of multibacterial infection, and the generated signals correlated
      well with the mix ratio. In summary, the gyrB-based pyrosequencing approach
      proved to have significant reliability and discriminatory power for
      enteropathogenic bacterial identification and provided a fast and effective
      method for clinical diagnosis.

PMID- 18324429
TI  - A comparison of signal detection techniques in the multifocal electroretinogram.
AB  - A common task in the analysis of the multifocal electroretinogram (mfERG) is
      determining which retinal areas have preserved signal in recordings which are
      attenuated by the effects of disease. Several automated methods have been
      proposed for signal detection from multifocal recordings, but no systematic study
      has been published comparing the performance of each. This article compares the
      sensitivity and specificity of expert human scoring with three different
      automated methods of mfERG signal detection. Recordings from control subjects
      were artificially modified to simulate decrease in signal amplitudes
      (attenuation) as well as total signal loss. Human scorers were able to identify
      areas with preserved signal at both low and high attenuation levels with a high
      specificity (minimum 0.99), sensitivities ranged from 0.2 to 0.94. Automated
      methods based on template correlation performed better than chance at all
      attenuation levels, with a slide fit method having the best performance. Signal
      detection based on signal to noise ratio performed poorly. In conclusion
      automated methods of signal detection can be used to increase signal detection
      sensitivity in the mfERG.

PMID- 18324430
TI  - Multifocal electroretinogram (mfERG) in patients with diabetes mellitus and an
      enlarged foveal avascular zone (FAZ).
AB  - PURPOSE: To assess the relationship between foveal microcirculation and central
      retinal function in diabetic patients having both an enlarged foveal avascular
      zone (FAZ) and a preserved visual acuity (0.6 or better). METHODS: Twenty-five
      patients with diabetes type 1 or 2 with an enlarged FAZ (largest diameter > 650
      microm) measured in fluorescein angiograms were examined with multifocal ERG
      (mfERG). The largest FAZ diameter, the FAZ area as well as the adjacent
      perifoveal intercapillary area (PIA), was calculated from the fluorescein
      angiogram. The retinopathy level was mild to preproliferative. There was no
      macular edema and no eye had previously been treated with photocoagulation.
      RESULTS: The mean FAZ diameter was 0.92 +/- 0.17 mm and the mean summed area (FAZ
      and PIA) was 0.74 +/- 0.24 mm(2). There was a significant correlation between
      increasing FAZ diameter and increasing implicit time of the innermost concentric
      rings and of the third concentric ring in the first order kernel of the mfERG (P
      = 0.03 and P = 0.008, respectively). An increasing summed area (FAZ and PIA) was
      correlated to increasing implicit time in the same areas of the mfERG (P = 0.005
      and P = 0.026, respectively). No correlation was seen between the ischemic areas
      and the mfERG amplitudes. CONCLUSION: A correlation between the ischemic areas
      and prolonged implicit time in the mfERG indicates that alterations in neuronal
      macular function due to ischemia might precede the deterioration of visual
      acuity.

PMID- 18324431
TI  - Wall shear stress as measured in vivo: consequences for the design of the
      arterial system.
AB  - Based upon theory, wall shear stress (WSS), an important determinant of
      endothelial function and gene expression, has been assumed to be constant along
      the arterial tree and the same in a particular artery across species. In vivo
      measurements of WSS, however, have shown that these assumptions are far from
      valid. In this survey we will discuss the assessment of WSS in the arterial
      system in vivo and present the results obtained in large arteries and arterioles.
      In vivo WSS can be estimated from wall shear rate, as derived from non-invasively
      recorded velocity profiles, and whole blood viscosity in large arteries and
      plasma viscosity in arterioles, avoiding theoretical assumptions. In large
      arteries velocity profiles can be recorded by means of a specially designed
      ultrasound system and in arterioles via optical techniques using fluorescent flow
      velocity tracers. It is shown that in humans mean WSS is substantially higher in
      the carotid artery (1.1-1.3 Pa) than in the brachial (0.4-0.5 Pa) and femoral
      (0.3-0.5 Pa) arteries. Also in animals mean WSS varies substantially along the
      arterial tree. Mean WSS in arterioles varies between about 1.0 and 5.0 Pa in the
      various studies and is dependent on the site of measurement in these vessels.
      Across species mean WSS in a particular artery decreases linearly with body mass,
      e.g., in the infra-renal aorta from 8.8 Pa in mice to 0.5 Pa in humans. The
      observation that mean WSS is far from constant along the arterial tree implies
      that Murray's cube law on flow-diameter relations cannot be applied to the whole
      arterial system. Because blood flow velocity is not constant along the arterial
      tree either, a square law also does not hold. The exponent in the power law
      likely varies along the arterial system, probably from 2 in large arteries near
      the heart to 3 in arterioles. The in vivo findings also imply that in in vitro
      studies no average shear stress value can be taken to study effects on
      endothelial cells derived from different vascular areas or from the same artery
      in different species. The cells have to be studied under the shear stress
      conditions they are exposed to in real life.

PMID- 18324432
TI  - Decomposition cross-correlation for analysis of collagen matrix deformation by
      single smooth muscle cells.
AB  - Microvascular remodeling is known to depend on cellular interactions with matrix
      tissue. However, it is difficult to study the role of specific cells or matrix
      elements in an in vivo setting. The aim of this study is to develop an automated
      technique that can be employed to obtain and analyze local collagen matrix
      remodeling by single smooth muscle cells. We combined a motorized microscopic
      setup and time-lapse video microscopy with a new cross-correlation based image
      analysis algorithm to enable automated recording of cell-induced matrix
      reorganization. This method rendered 60-90 single cell studies per experiment,
      for which collagen deformation over time could be automatically derived. Thus,
      the current setup offers a tool to systematically study different components
      active in matrix remodeling.

PMID- 18324433
TI  - A game theoretical approach to the evolution of structured communication codes.
AB  - Structured meaning-signal mappings, i.e., mappings that preserve neighborhood
      relationships by associating similar signals with similar meanings, are
      advantageous in an environment where signals are corrupted by noise and sub
      optimal meaning inferences are rewarded as well. The evolution of these mappings,
      however, cannot be explained within a traditional language evolutionary game
      scenario in which individuals meet randomly because the evolutionary dynamics is
      trapped in local maxima that do not reflect the structure of the meaning and
      signal spaces. Here we use a simple game theoretical model to show analytically
      that when individuals adopting the same communication code meet more frequently
      than individuals using different codes-a result of the spatial organization of
      the population-then advantageous linguistic innovations can spread and take over
      the population. In addition, we report results of simulations in which an
      individual can communicate only with its K nearest neighbors and show that the
      probability that the lineage of a mutant that uses a more efficient communication
      code becomes fixed decreases exponentially with increasing K. These findings
      support the mother tongue hypothesis that human language evolved as a
      communication system used among kin, especially between mothers and offspring.

PMID- 18324434
TI  - Hematoporphyrin-mediated fluorescence reflectance imaging: application to early
      tumor detection in vivo in small animals.
AB  - The in vivo early detection of subcutaneous human tumors implanted in small
      animals was studied by laser-induced fluorescence reflectance imaging (FRI), with
      a hematoporphyrin (HP) compound as an exogenous optical contrast agent. Tumor
      detection was shown to be possible just 3 days after the inoculation of tumor
      cells, when tumors were neither visible nor palpable. However, this detection
      capability is limited to a temporal window of approximately 100 h from HP
      administration and to a low optical contrast of the tumor (<2).

PMID- 18324435
TI  - Biostraticola tofi gen. nov., spec. nov., a novel member of the family
      Enterobacteriaceae.
AB  - Bacterial strain BF36T, isolated from the biofilm of a tufa deposit in a hard
      water rivulet, was characterized by a polyphasic taxonomic approach. Cells of
      these organisms were Gram-negative, motile, nonpigmented, rod-shaped, non
      endospore-forming, and facultatively anaerobic. Cells, organized in loose
      consortia, were coated by a massive slime layer. Phylogenetic analyses using 16S
      rRNA gene sequences showed that strain BF36T was a member of the family
      Enterobacteriaceae, class Gammaproteobacteria, displaying a moderate degree of
      relationship (96.5% sequence similarity) to Sodalis glossinidius and "Sodalis
      pallipedes," intracellular symbionts of the tsetse fly Glossinis morsitans
      morsitans. Dendrograms of relationship generated by different algorithms
      consistently grouped isolate BF36T with Sodalis glossinidius, Pragia fontium,
      Budvicia aquatica, Serratia rubideae, and Brenneria spp (94.7-95.8% similarity)
      which also share many common metabolic properties. Differences between strain
      BF36T and Sodalis glossinidius DSM 13495T are seen in motility and in the pattern
      of substrates utilized. Membership to the family was also confirmed by a fatty
      acid profile consisting of major amounts of C16:0)and C16:1omega7, by the
      presence of isoprenoids of the ubiquinone Q8 and menaquinone MK8 types and a DNA
      G + C content of 54.2 mol%. The decision to classify strain BF36T into a new
      genus Biostraticola gen. nov. is based on its distant phylogenetic position as
      compared to any other representative of the family and the significant phenotypic
      differences to its nearest phylogenetic neighbor, Sodalis glossinidius. BF36T
      represents the type species, for which the name Biostraticola tofi sp. nov. is
      proposed. The type strain is BF36T (DSM 19580T; CIP109699T).

PMID- 18324436
TI  - Conservation of sigma F in mycobacteria and its expression in Mycobacterium
      smegmatis.
AB  - Alternate sigma factor SigF controls the expression of virulence-associated genes
      and is believed to contribute to the pathology of tuberculosis. It was reported
      to be absent in fast-growing nontuberculous mycobacteria until its orthologs were
      reported recently in a database. In this study, we demonstrate the presence of
      sigF gene in few commonly studied nonpathogenic mycobacterial species. Further,
      we studied the sigF expression in Mycobacterium smegmatis and observed that
      unlike its late-stage expression in M. tuberculosis and M. bovis, found in
      earlier studies, sigF is expressed throughout the growth in M. smegmatis, by and
      large, at the same level, but its expression varies upon exposure to different
      stress conditions. The presence of sigF orthologs in nontuberculous mycobacteria
      and its continued expression throughout the growth suggests that apart from
      regulating the expression of virulence factor genes in pathogenic mycobacteria,
      SigF is likely to have more roles in the mycobacterial physiology.

PMID- 18324437
TI  - Diversity of nifH genotypes in floating periphyton mats along a nutrient gradient
      in the Florida Everglades.
AB  - Periphyton mats are an important component of many wetland ecosystems, performing
      a range of vital ecosystem functions, including nitrogen fixation. The
      composition and integrity of these mats are affected by nutrient additions, which
      might result in changes in their function. The overall objective of this study
      was to investigate the distribution of nifH sequences in floating periphyton mats
      collected along a nutrient gradient in the Florida Everglades. Distribution of
      nifH clone libraries indicated nutrient enrichment selected primarily for
      sequences branching deeply within the heterocystous cyanobacteria and within a
      novel group of cyanobacteria; sequences from low-nutrient sites were broadly
      distributed, with no clear dominance of sequences associated with heterocystous
      and nonheterocystous cyanobacteria and alpha-, gamma-, and delta-proteobacteria.
      The dominance of heterocystous cyanobacteria in nutrient-enriched sites and the
      lack of clear dominance by heterocystous cyanobacteria is consistent with
      previously reported diurnal cycles of nitrogen fixation rates in these systems.
      Sequences clustering with those harbored by methanotrophs were also identified;
      sequences from nutrient-impacted and transition regions clustered with those
      characteristic of type II methanotrophs, and sequences from oligotrophic regions
      clustered with type I methanotrophs.

PMID- 18324438
TI  - Closely linked non-additive blood pressure quantitative trait loci.
AB  - There is enough evidence through linkage and substitution mapping to indicate
      that rat chromosome 1 harbors multiple blood pressure (BP) quantitative trait
      loci (QTLs). Of these, BP QTL1b was previously reported from our laboratory using
      congenic strains derived by introgressing normotensive alleles from the LEW rat
      onto the genetic background of the hypertensive Dahl salt-sensitive (S) rat. The
      region spanned by QTL1b is quite large (20.92 Mb), thus requiring further mapping
      with improved resolution so as to facilitate systematic identification of the
      underlying genetic determinant(s). Using congenic strains containing the LEW rat
      chromosomal segments on the Dahl salt-sensitive (S) rat background, further
      iterations of congenic substrains were constructed and characterized. Collective
      data obtained from this new iteration of congenic substrains provided evidence
      for further fragmentation of QTL1b with improved resolution. At least two
      separate genetic determinants of blood pressure underlie QTL1b. These are within
      7.40 Mb and 7.31 Mb and are known as the QTL1b1 region and the QTL1b2 region,
      respectively. A genetic interaction was detected between the two BP QTLs.
      Interestingly, five of the previously reported differentially expressed genes
      located within the newly mapped QTL1b1 region remained differentially expressed.
      The congenic strain S.LEW(D1Mco36-D1Mco101), which harbors the QTL1b1 region
      alone but not the QTL1b2 region, serves as a genetic tool for further dissection
      of the QTL1b1 region and validation of Nr2f2 as a positional candidate gene.
      Overall, this study represents an intermediary yet obligatory progression towards
      the identification of genetic elements controlling BP.

PMID- 18324439
TI  - Modified hemi-double-stapling technique combined with the temporal abdominal-wall
      lift method for performing Billroth I anastomosis after laparoscopically assisted
      distal gastrectomy.
AB  - The authors have used a modified hemi-double-stapling (HDS) technique for
      reconstruction after laparoscopically assisted distal gastrectomy. The stomach is
      resected from the greater curvature side using a linear stapler inserted into the
      stomach from that side at a position vertical to the line of the greater
      curvature. Resection of the stomach is performed by extending the resection line
      to the lesser curvature using laparoscopic coagulating shears. The resected
      specimen is examined. After placement of a purse-string suture at the duodenal
      stump, an anvil is inserted into the stump, and an additional suture with 2-0
      silk is placed over the purse-string suture. A curved intraluminal stapler
      (CDH25) is inserted into the stomach through the opening made on the lesser
      curvature side, and the center rod of the stapler is passed through the gastric
      wall on the corner of the resection line at the greater curvature. Ligation with
      2-0 silk is added to the center rod by suturing the gastric tissue 5-8 mm from
      the center rod to encircle it. The authors call this the "one-knot setup HDS,"
      and with this method, a large-caliber anastomosis is secured. In many cases, it
      is difficult to observe the anastomotic site through the small incisional
      opening. However, under laparoscopy with the temporal abdominal wall-lift method
      using the Multi Flap Gate, the anastomotic site can be easily and safely
      observed. One-knot setup HDS combined with the temporal abdominal wall-lift
      method is considered a safe and simple method for performing Billroth I
      anastomosis in laparoscopic distal gastrectomy.

PMID- 18324440
TI  - Perianal streptococcal dermatitis: an important differential diagnosis in
      pediatric patients.
AB  - Perianal streptococcal dermatitis is an infectious disease that predominantly
      affects younger children and is mostly caused by Group A beta-hemolytic
      streptococci. Although patients are mostly seen primarily by their pediatrician
      or family physician, the diagnosis is not infrequently established just after
      referral to a dermatologist or colorectal surgeon. We report a case series of 124
      children, aged 14 years or younger, who were seen at our office for anorectal
      complaints between February 2003 and September 2006. Twenty-one of 124 patients
      (16 percent) were diagnosed with perianal streptococcal dermatitis on the basis
      of a positive perianal swab by microbiologic analysis. Perianal streptococcal
      dermatitis was the most frequent infectious disease in that age group in our
      practice. Sixteen (of 21, 76 percent) patients were male, and the mean age was
      6.3 years. One course of systemic antibiotic treatment augmented by additional
      local antiseptic ointment in selected cases cured all patients within 10 to 14
      days. One patient presented with a new perianal streptococcal dermatitis episode
      five months after treatment and was successfully retreated with an oral
      antibiotic. With this report, we wish to alert the colorectal community of the
      diagnosis because it may be underdiagnosed in our practices and thereby lead to
      prolonged discomfort, protracted disease, and potentially harmful sequelae for
      these typically very young patients.

PMID- 18324441
TI  - Papillary thyroid carcinoma: factors influencing recurrence and survival.
AB  - BACKGROUND: The prognosis of patients with papillary thyroid carcinoma (PTC) is
      usually favorable; however, a subset of patients can develop local recurrence or
      distant metastases. The aim of this study was to evaluate the prognostic factors
      influencing the recurrence and the survival rate in 950 PTC patients. MATERIALS
      AND METHODS: From 1990 to 2005, 950 consecutive patients affected by PTC were
      operated on at our Department. We analyzed the prognostic role of the following
      parameters: gender, age at initial treatment, extent of thyroid surgery, node
      dissection, tumor size, node metastases, distant metastases, stage, and 131-I
      therapy. RESULTS: Seventy-nine patients (8.3%) developed locoregional or distant
      metastases after an average follow-up of 7.8 years (range 2-17 years); in
      particular local recurrence was observed in 25 cases and distant metastases in 54
      cases. The global 10- and 15-year survival rates were 91.38% and 88.69%,
      respectively. At univariate analysis, all variables were significantly correlated
      with recurrence (P = .001) except gender (P = .3); moreover, gender (P = .2),
      node dissection (P = .5), and node metastases (P = .06) were not significant on
      10- and 15-year survival. At multivariate analysis the age at first treatment,
      T4, M+, stage IV, the extent of thyroid surgery, and the 131-I therapy resulted
      to be significant and independent prognostic factors (P < .001). CONCLUSION: Our
      data, in disagreement with other staging systems, suggest that gender does not
      play a significant role both in recurrence and survival. Moreover, the 131-I
      therapy was a statistically significant prognostic factor at univariate and
      multivariate analyses.

PMID- 18324442
TI  - Sentinel nodes in breast cancer: relevance of axillary level II nodes and optimal
      number of nodes that need to be removed.
AB  - BACKGROUND: In some patients, the radiocolloid used to perform sentinel lymph
      node biopsy (SLNB) for breast cancer appears in a number of lymph nodes and in
      different levels of the axilla. Most positive sentinel lymph node specimens
      (SLNSs) removed during SLNB are identified in level I of the axilla and within
      the first 4 SLNSs. Our objective was to verify the staging accuracy of harvesting
      only the first 4 SLNSs and to determine the relevance of SLNSs that reside in
      level II of the axilla. METHODS: A prospective database documenting the method of
      identification, radioisotope count, order of retrieval, and axillary level of
      SLNSs from 893 SLNBs was analyzed. RESULTS: A median of 2 SLNSs (range 1-9) were
      removed per patient. More than 4 SLNSs were found in 8.0%. All SLNSs harboring
      the largest nodal metastases were identified within the first 4 harvested. Twenty
      one percent (184 of 870) of patients had level II SLNSs; 4.9% (9 of 184) were
      positive. When SLNSs were positive in both levels I and II, the nodal metastases
      were always of greater or equal size in the level I nodes. Only one patient
      (0.5%) had a positive level II SLNS macrometastasis (> 2 mm, pN1), with a
      negative level I SLNS, but it was the hottest node and was removed first.
      CONCLUSIONS: Removal of more than the first 4 hottest SLNSs does not improve
      staging accuracy. Level II nodes can be ignored if a hotter level I SLNS is first
      identified.

PMID- 18324443
TI  - Microvascular invasion in patients with hepatocellular carcinoma and its
      predictable clinicopathological factors.
AB  - BACKGROUND: Macroscopic vascular invasion is known to be a poor prognostic factor
      in hepatocellular carcinoma (HCC). The aim of this study was to determine the
      outcomes and predictive factors after hepatic resection for HCC with
      microvascular invasion (MVI). METHODS: One hundred ten patients who underwent
      curative resection for HCC without macroscopic vascular invasion were included in
      this retrospective study. The risk factors of these patients for recurrence-free
      and disease-specific survival were investigated, and the clinicopathological
      factors predicting the presence of MVI were also determined. RESULTS: Of the 110
      resected specimens, 49 (45%) had evidence of MVI. By univariate analysis, MVI was
      found to be statistically significantly associated with greater tumor size, gross
      classification, histological grade, and intrahepatic micrometastasis. Gross
      classification proved to be the only independent predictive factor for MVI by
      multiple logistic regression analysis. By multivariate analysis, cirrhosis and
      MVI were identified as independent risk factors for recurrence-free survival. The
      5-year recurrence-free survival rates for patients with and without MVI were
      20.8% and 52.6%, respectively. By multivariate analysis, the number of tumors,
      presence of MVI, and intrahepatic micrometastasis were identified as independent
      predictors of disease-specific survival. The 5-year disease-specific survival
      rates for patients with and without MVI were 59.3% and 92.0%, respectively.
      CONCLUSIONS: The presence of MVI was the most important risk factor affecting
      recurrence and survival in HCC patients after curative resection. Furthermore,
      this study showed that gross classification of HCC can be very helpful in
      predicting the presence of MVI.

PMID- 18324444
TI  - Tumor-positive sentinel node biopsy of the groin in clinically node-negative
      melanoma patients: superficial or superficial and deep lymph node dissection?
AB  - BACKGROUND: The extent of a completion groin dissection in sentinel node-positive
      melanoma patients was guided by the location of the second-echelon nodes on the
      preoperative lymphoscintigram. The purposes of the current study were to
      investigate the pathological findings, the lymph node recurrences and (disease
      free) survival associated with this approach. METHODS: Between June 1996 and
      April 2007, 42 patients underwent completion groin dissection after a tumor
      positive sentinel node biopsy. Eighteen patients had femoro-inguinal second
      echelon nodes on their lymphoscintigram and underwent a superficial lymph node
      dissection. Twenty-four patients had iliac-obturator second-echelon nodes found
      by scan and underwent a combined superficial and deep dissection. RESULTS: The
      median follow-up time was 61 months. One of the 18 patients who underwent a
      superficial groin dissection developed a deep (obturator) lymph node recurrence
      after 12 months. Revision of the lymphoscintigram showed that the images had been
      interpreted incorrectly and that the second-echelon node was located in the
      obturator area after all. A combined superficial and deep dissection revealed
      additional involved nodes in the deep lymph node compartment in 2 of the 24
      patients. At 5 years, 77% of all patients were alive, and 56% were alive and free
      of disease. These figures were 76% and 53%, respectively, in the patients who
      underwent superficial dissection only, and 80% and 61%, respectively, in the
      patients who also underwent deep dissection. CONCLUSIONS: This study suggests
      that a strategy to determine the extent of the groin dissection that is based on
      the location of the second-tier nodes may be valid.

PMID- 18324445
TI  - HIPEC: the complexities of clinical trials.

PMID- 18324446
TI  - Fewer infectious manifestations are induced by bacteria entrapped in cholesterol
      stones than by bacteria in brown pigment gallstone.

PMID- 18324447
TI  - Early experience with intraluminal reinforcement of stapled gastrojejunostomy
      during laparoscopic Roux-en-Y gastric bypass.
AB  - BACKGROUND: The use of extraluminal staple-line buttressing material during
      laparoscopic Roux-en-y gastric bypass has shown the potential to reduce staple
      line leak and bleeding. We herein present our early experience with intraluminal
      reinforcement of linear-cutting stapled gastrojejunal anastomosis with the use of
      bioabsorbable glycolide copolymer staple-line reinforcement. METHODS:
      Laparoscopic Roux-en-Y gastric bypass was performed in 80 consecutive non
      randomized morbidly obese patients. Gastrojejunal anastomosis was performed using
      a linear-cutting stapler without staple-line reinforcement in 40 patients (group
      A), while in the other 40 patients (group B), gastrojejunostomy was performed
      using a linear cutting stapler with intraluminal reinforcement material
      (bioabsorbable glycolide copolymer). Demographic data were collected. The rate of
      gastrojejunal anastomotic leak, bleeding, and stricture was determined. RESULTS:
      There was a statistically significant reduction in bleeding complications between
      the two groups (15% bleeding in group A vs. no bleeding in group B, P
      value=0.0255). Stricture rate was higher in-group A (10% group A vs. 2.5% in
      group B); however, the difference was not statistically significant (P
      value=0.2007). None of our patients developed a gastrojejunal leak. CONCLUSION:
      Intraluminal reinforcement of gastrojejunal anastomosis during laparoscopic
      gastric bypass is safe and feasible. The use of intraluminal bioabsorbable
      glycolide copolymer staple-line reinforcement significantly reduces the incidence
      of gastrojejunal bleeding.

PMID- 18324448
TI  - Predictors of weight loss and effectiveness of Roux-en-Y gastric bypass in the
      morbidly obese Hispano-American population.
AB  - BACKGROUND: Co-morbidities and the metabolic response to intervention in morbid
      obesity have been reported to vary among different ethnic groups. We compared the
      rate of weight loss, effectiveness of gastric bypass surgery, and variables
      influencing success after gastric bypass in Hispanics compared to Caucasians.
      METHODS: Morbidly obese adult (>18 years old) patients (body mass index [BMI] 40
      or above) evaluated by our bariatric group from 2005 to 2006 who underwent Roux
      en-Y gastric bypass (RYGBP) were studied. Every patient was evaluated for height,
      weight, BMI, percent body fat, fat mass, serum metabolic analysis (SMA) 12, lipid
      profile, complete blood count (CBC), iron, ferritin, Vitamins A, D, and B1,
      complete urinalysis and Fibrospect score II. Weight loss was evaluated at 1, 3,
      6, and 12 months. RESULTS: Seventy-five patients underwent successful open RYGBP
      with no mortality. Regardless of the significant difference in age and co
      morbidities, the mean percentage of total weight loss after 1 year of follow-up
      was 32% for Hispanics and 30% for Caucasians with no significant difference (p >
      .5). When comparing the percentage of excess weight lost (% EWL) at 1, 3, 6, and
      12 months, there was no significant difference between both groups. Using
      multiple regression analysis, we found that high-density lipoprotein (HDL) and
      systolic blood pressure (SBP) significantly predicted EWL at 12 months in
      Caucasians and Fibrospect predicted significantly EWL at 1 year. CONCLUSION: At 1
      year after RYGBP, both ethnic groups lost approximately 77-80% of their EWL and
      BMI. All Caucasians and 95.7% of Hispanics achieved successful weight loss (>50%
      EWL).

PMID- 18324450
TI  - Seven cases of gastric perforation in Roux-en-Y gastric bypass patients: what
      lessons can we learn?
AB  - BACKGROUND: Patients undergoing Roux-en-Y gastric bypass for the resolution of
      morbid obesity have significant medical sequelae related to their weight. One of
      the most common comorbid conditions is joint pain requiring the use of non
      steroidal anti-inflammatory medications (NSAIDs). In addition to NSAIDs, patients
      may engage in behaviors such as smoking and alcohol misuse that increase the risk
      of long-term postoperative complications to include gastric perforation. METHODS:
      Data on 1,690 patients undergoing gastric bypass surgery were collected
      prospectively and reviewed retrospectively. RESULTS: We identified seven patients
      who presented to an emergency room and subsequently required emergent surgical
      intervention for repair of gastric perforation. Six of the seven cases involved
      use or abuse of NSAIDs. CONCLUSION: Important characteristics were identified
      including the use of NSAIDs, alcohol use, and non-compliance with routine long
      term postoperative follow-up. Identifying those patients at high risk may
      decrease the incidence of this potentially life-threatening complication.

PMID- 18324451
TI  - Hybrid total knee arthroplasty: 13-year survivorship of AGC total knee systems
      with average 7 years followup.
AB  - A retrospective study of 201 anatomic graduated component total knee
      arthroplasties implanted with hybrid fixation at the authors' center was
      performed in response to conflicting data in the literature concerning the
      benefits of a hybrid method. Selection for hybrid fixation was nonrandomized and
      based on femoral component fit. Survivorship analysis was performed, and rates of
      radiolucent lines surrounding the femoral component and occurrence of osteolysis
      were noted. At 7 and 13 years, survivorship with tibial or femoral revision as
      the end point was 0.9926 and 0.9732, respectively. Radiolucencies were found
      adjacent to 15 femoral components at final followup (seven in Zone 1, three in
      Zone 2, five in Zone 3, one in Zone 4, two in Zone 5, zero in Zone 6). Osteolysis
      was observed in one knee after secondary evaluation. Hybrid fixation in a
      selected patient population can result in excellent results in middle to long
      term followup.

PMID- 18324452
TI  - Readability of online patient education materials from the AAOS web site.
AB  - One of the goals of the American Academy of Orthopaedic Surgeons (AAOS) is to
      disseminate patient education materials that suit the readability skills of the
      patient population. According to standard guidelines from healthcare
      organizations, the readability of patient education materials should be no higher
      than the sixth-grade level. We hypothesized the readability level of patient
      education materials available on the AAOS Web site would be higher than the
      recommended grade level, regardless when the material was available online.
      Readability scores of all articles from the AAOS Internet-based patient
      information Web site, "Your Orthopaedic Connection," were determined using the
      Flesch-Kincaid grade formula. The mean Flesch-Kincaid grade level of the 426
      unique articles was 10.43. Only 10 (2%) of the articles had the recommended
      readability level of sixth grade or lower. The readability of the articles did
      not change with time. Our findings suggest the majority of the patient education
      materials available on the AAOS Web site had readability scores that may be too
      difficult for comprehension by a substantial portion of the patient population.

PMID- 18324453
TI  - Rapid frequency-domain FLIM spinning disk confocal microscope: lifetime
      resolution, image improvement and wavelet analysis.
AB  - A spinning disk confocal attachment is added to a full-field real-time frequency
      domain fluorescence lifetime-resolved imaging microscope (FLIM). This provides
      confocal 3-D imaging while retaining all the characteristics of the normal 2-D
      FLIM. The spinning disk arrangement allows us to retain the speed of the normal 2
      D full field FLIM while gaining true 3-D resolution. We also introduce the use of
      wavelet image transformations into the FLIM analysis. Wavelets prove useful for
      selecting objects according to their morphology, denoising and background
      subtraction. The performance of the instrument and the analysis routines are
      tested with quantitative physical samples and examples are presented with complex
      biological samples.

PMID- 18324454
TI  - Retinoic acid-induced testosterone production and retinoylation reaction are
      concomitant and exhibit a positive correlation in Leydig (TM-3) cells.
AB  - Retinoic acid (RA) exerts diverse biological effects in the control of cell
      growth in embryogenesis and oncogenesis. The effects of RA are thought to be
      mediated by the nuclear retinoid receptors; however, not all the effects of RA
      can be explained by the nuclear receptor pathways. Indeed, retinoylation is
      another mechanism of action elicited by RA. In growing TM-3 Leydig cell cultures,
      the extent of retinoylation depends in a saturable manner on the initial
      concentration of 3H-RA, time and cell number. In addition, dose-response curves
      for RA-induced testosterone production and retinoylation are concomitant and
      exhibit a positive correlation. In the present study we demonstrate that RA is
      able to influence a retinoylation reaction on protein(s) probably involved on
      steroidogenesis.

PMID- 18324455
TI  - Successful use of "cryo-mapping" to avoid phrenic nerve damage during ostial
      superior vena caval ablation despite nerve proximity.
AB  - BACKGROUND: The SVC may require ablation to treat atrial fibrillation. Phrenic
      nerve proximity identified with pacing maneuvers may preclude ablation. METHODS:
      We tested a new method using "cryo-mapping" to ablate despite nerve proximity.
      RESULTS: Of 833 patients undergoing ablation, 110 (12%) had arrhythmogenic
      substrate at the SVC/RA junction. Of these 110 patients, 66 (60%) had consistent
      diaphragmatic stimulation when pacing at 10 mA at the prospective site of
      ablation. Of these 66 patients, 7 had continued arrhythmogenicity despite
      attempts to modify this substrate. For these 7 patients, we paced 4 cm into the
      SVC where consistent phrenic nerve stimulation was obtained, and cryoablation at 
      30 degrees C was performed at sites requiring ablation. In 6 of 7 patients (86%),
      with continued diaphragmatic capture, cryoablation at -70/-80 degrees C was then
      performed. In 1 of 7 patients (14%), diaphragmatic stimulation ceased at -30
      degrees C, and energy delivery stopped. In the 6 patients in whom cryoablation
      was completed, the arrhythmogenic substrate was successfully ablated without
      phrenic nerve injury. CONCLUSIONS: A novel "cryo-mapping" technique during
      phrenic nerve pacing can be used to successfully ablate arrhythmogenic substrate
      at the SVC/RA junction despite phrenic nerve proximity.

PMID- 18324456
TI  - Impact of pre-existent areas of complex fractionated atrial electrograms on
      outcome after pulmonary vein isolation.
AB  - BACKGROUND: Atrial fibrillation (AF) drivers outside pulmonary veins (PV) may
      account for failure after PV isolation. The aim of this study was to characterize
      pre-existent areas of complex fractionated atrial electrograms (CFAEs) recorded
      in right atrium (RA) and in coronary sinus (CS) during catheter-based PV
      isolation and to assess their relation to outcome. METHODS AND RESULTS: With a
      tricuspid annulus and CS mapping, CFAEs were retrospectively identified in
      consecutive patients who underwent PV isolation. Of 224 patients, 161 were found
      to have CFAEs (81%). No clinical variable was found to be predictive of CFAEs
      presence. By Kaplan-Meier analysis, following a median follow-up of 23.7 months
      after a single ablation procedure, 62.8% of patients in the CFAEs+ group and
      85.4% of those in the CFAEs- group were free from recurrent atrial
      tachyarrhythmias (p=0.013). Multivariable Cox regression analysis showed that
      CFAEs evidence was an independent predictor of recurrence (p=0.007). CONCLUSIONS:
      Pre-existent CFAEs, that can be easily identified in RA and CS during PV
      isolation, are a powerful independent predictor for AF recurrence. This finding
      may be helpful for refining AF ablation strategies.

PMID- 18324457
TI  - Medium- and long-term survival after pacemaker implant: Improved survival with
      right ventricular outflow tract pacing.
AB  - INTRODUCTION: Long-term prognosis after pacemaker implant depends on numerous
      variables, particularly structural heart disease. There is evidence that apical
      stimulation could favor the development of heart failure and, therefore,
      influence mortality. Other right ventricular pacing sites have been studied, for
      example the outflow tract, but no reports regarding long-term clinical outcome
      are available. OBJECTIVE: Compare all-cause mortality between two different sites
      of stimulation in the right ventricle. METHODS: We retrospectively analyzed 150
      consecutive patients who underwent pacemaker implantation because of complete AV
      block (spontaneous or after AV node ablation), symptomatic second-degree AV
      block, and symptomatic atrial fibrillation with slow ventricular response. All
      patients were implanted at the same institution with the standard technique.
      Apical stimulation was performed with a passive or active fixation lead and
      outflow tract pacing with an active fixation lead. Data collection period began
      in July 1999 and ended on December 2004. All patients included were greater than
      70% ventricular paced during pacemaker follow-up. Patients older than 85 years
      were excluded from the analysis. Age, pacemaker mode, sex, ejection fraction,
      diabetes, and structural cardiac disease were analyzed. Mean age was 72+/-7 years
      (median 74 years, range 27-85 years), 101 (67%) were male, 56 had implanted a VVI
      PM, and 94 patients a DDD PM. Patients were divided into two groups: outflow
      tract (55 patients) and apical pacing (95 patients). Mean follow-up was 1,231+/
      642 days (median 1,158 days, range 9 to 2,694 days), which ended on July 2007.
      Total mortality was examined with the Kaplan-Meier method to construct overall
      survival curves. Multivariate Cox proportional hazards regression models were
      performed. RESULTS: All patients or relatives were contacted personally or by
      phone. There were no major statistical differences in patient background between
      the two groups. During follow-up, 18 patients (32%) died in the outflow tract
      group and 49 (51%) in the apical group (log-rank p=0.02). Cox regression
      multivariate analysis showed that outflow tract pacing and a low left ventricular
      ejection fraction (<40%) were the only independent variables with significant
      correlation with survival (p=0.006 and 0.003, respectively). CONCLUSIONS: Outflow
      tract pacing appears to improve medium- and long-term survival. Prospective
      randomized trials with a greater amount of patients are necessary to confirm the
      findings of this study.

PMID- 18324458
TI  - Age and gender trends in implantable cardioverter defibrillator utilization: a
      population based study.
AB  - INTRODUCTION: Implantable cardioverter-defibrillators improve mortality in
      selected high risk patients, yet population based data regarding utilization of
      these devices, particularly in the elderly, are limited. METHODS: To address
      this, we reviewed all ICD implantations performed in Olmsted County, MN, a
      geographically defined population, between December 1989 and December 2004.
      RESULTS: The study population comprised 179 patients (147 male, 82%, mean age 65
      +/- 14 years). Baseline ejection fraction and creatinine were 35% +/- 16% and
      1.38 +/- 1.08 mg/dl, respectively. Over the study period, the incidence of
      congestive heart failure in patients undergoing ICD implantation and referrals
      for primary prevention ICDs increased, while baseline ejection fraction and
      etiology of cardiomyopathy remained unchanged. The incidence of ICD implantations
      increased significantly in the elderly (p < 0.001) and especially in male
      patients when compared to female patients (p < 0.001). CONCLUSIONS: Age of
      patients undergoing ICD implantation is increasing. However, fewer females
      compared to males are undergoing ICD implantation, suggesting a gender bias in
      ICD therapy and utilization.

PMID- 18324459
TI  - Anatomical pitfalls during encircling cryoablation of the left atrium for atrial
      fibrillation therapy in the pig.
AB  - We previously published encircling endocardial cryo-isolation of the pulmonary
      vein (PV) region. This study documented mechanisms of isolation failure using
      CARTO mapping. Cryo-isolation used a modified Surgifrost introduced via a
      Universal Cardiac Introducer on the left atrial appendage. Of five pigs, two had
      incomplete isolation and repeat mapping: Activation was over Bachmann's bundle
      (BB) in one and the coronary sinus (CS) in the other. Repeat cryoablation failed
      to eliminate gaps. Histologically, the BB gap had nonlesioned sub-epicardial
      fibres and thick fat covering the cryolesioned BB: fat protecting the epicardium
      from cryoablation. The inferior gap had a large CS, and a thick myocardium
      bridging the isthmus: myocardial thickness and CS thermal sink preventing
      transmural cryolesions. CARTO mapping localized gaps. Although the CS is known to
      cause failure, its protective mechanism is not well documented. The BB gap is
      novel. These findings have important clinical implications for isolation of the
      PV region.

PMID- 18324460
TI  - Concepts of burden in giving care to older relatives: a study of female
      caregivers in a Mexico City neighborhood.
AB  - This study examined how women in a Mexico City suburb conceptualized the
      construct of burden within the context of giving care to older relatives. Data
      were collected on 41 women through semi-structured interviews regarding their
      caregiving experiences to elderly relatives. Phenomenological principles were
      used to analyze meanings and understandings of caregiving experiences. Burden was
      a multi-dimensional construct that referred to specific situations that made
      caregivers feel emotionally or physical "heavy." Burden also referred to "being a
      burden" by being in the way, making things difficult, or being a 'weight' on
      caregivers' shoulders. However, women in this study also viewed burden as a
      positive sacrifice that involved love, initiative, and good will. This study is
      an important first step in defining the ways in which caregiving is positively
      and negatively meaningful for Mexican caregivers and their families. Our findings
      offer an additional dimension of caregiver burden to broaden our understanding
      and measurement of the construct. The development of culturally appropriate
      instruments to measure caregiving burden in Mexico is necessary to provide an
      empirical foundation for policy recommendations that address the growing need for
      institutional support of caregivers. Moreover, our findings suggest that
      researchers studying caregiving in Mexico should think about how burden is
      measured on existing instruments before adapting them for widespread use.

PMID- 18324461
TI  - Social anxiety in high-functioning children and adolescents with Autism and
      Asperger syndrome.
AB  - We examined social anxiety and internalizing symptoms using the Social Phobia and
      Anxiety Inventory for Children (SPAI-C), the Social Anxiety Scale for Children 
      Revised (SASC-R), and the Child Behavior Checklist (CBCL) in a sample of fifty
      four high-functioning subjects with autism or Asperger syndrome (HFA/AS) (M =
      11.2 +/- 1.7 years) and 305 community subjects (M = 12.2 +/- 2.2 years). Children
      and adolescents completed the SPAI-C and SASC-R, and their parents completed the
      CBCL Internalizing scale. Adolescents with HFA/AS scored higher than the
      community sample on all measures. Behavioural avoidance and evaluative social
      anxiety increased by age within the HFA/AS group, whereas behavioural avoidance
      decreased by age in control participants. Data support that HFA/AS in adolescents
      may be associated with clinically relevant social anxiety symptoms.

PMID- 18324462
TI  - Male brains, androgen, and the cognitive profile in autism: convergent evidence
      from 2D:4D and congenital adrenal hyperplasia.

PMID- 18324463
TI  - Social behavior and autism traits in a sex chromosomal disorder: Klinefelter
      (47XXY) syndrome.
AB  - Although Klinefelter syndrome (47,XXY) has been associated with psychosocial
      difficulties, knowledge of the social behavioral phenotype is limited. We
      examined specific social abilities and autism traits in Klinefelter syndrome.
      Scores of 31 XXY men on the Scale for Interpersonal Behavior and the Autism
      Spectrum Questionnaire were compared to 24 and 20 control men respectively. XXY
      men reported increased distress during social interactions and less engagement in
      specific social behaviors. In the XXY group, levels of autism traits were
      significantly higher across all dimensions of the autism phenotype. These
      findings call for a clinical investigation of vulnerability to autism in
      Klinefelter syndrome. Klinefelter syndrome might serve as a model for studying a
      role of the X chromosome in social behavioral dysfunction and autism-like
      behavior.

PMID- 18324464
TI  - Language abilities of children with Asperger syndrome.
AB  - Current diagnostic taxonomies (ICD-10, DSM-IV) emphasize normal acquisition of
      language in Asperger syndrome (AS). Although many linguistic sub-skills may be
      fairly normal in AS there are also contradictory findings. There are only few
      studies examining language skills of children with AS in detail. The aim of this
      study was to study language performance in children with AS and their age, sex
      and IQ matched controls. Children with AS had significantly lower scores in the
      subtest of Comprehension of Instructions. Results showed that although many
      linguistic skills may develop normally, comprehension of language may be affected
      in children with AS. The results suggest that receptive language processes should
      be studied in detail in children with AS.

PMID- 18324465
TI  - Brief report: eye direction detection improves with development in autism.
AB  - Eye direction detection has been claimed to be intact in autism, but the
      development of this skill has not been investigated. Eleven children with autism
      and 11 typically developing children performed a demanding face-to-face eye
      direction detection task. Younger children with autism demonstrated a deficit in
      this skill, relative to younger control participants. Older children with autism
      were as accurate as older control participants on this task. In autism, eye
      direction detection is deficient in late childhood but is typically accurate by
      adolescence. The implications of this finding for models of social cognitive
      development in autism are considered.

PMID- 18324466
TI  - Comparison of diagnostic methods for asperger syndrome.
AB  - Several different diagnostic sets of criteria exist for Asperger syndrome (AS),
      but there is no agreement on a gold standard. The aim of this study was to
      compare four diagnostic sets of criteria for AS: the ICD-10, the DSM-IV, the
      Gillberg & Gillberg, and the Szatmari criteria. The series consists of 36
      children who had been referred to two centers with a tentative diagnosis of AS.
      The best agreement was between the ICD-10 and the DSM-IV criteria (Kappa
      coefficient 0.48), and the lowest between the Gillberg & Gillberg and Szatmari
      criteria (Kappa coefficient -0.21). The poor agreement between these sets of
      diagnostic criteria compromises the comparability of studies on AS.

PMID- 18324467
TI  - Obstetric and parental psychiatric variables as potential predictors of autism
      severity.
AB  - Associations between obstetric and parental psychiatric variables and subjects'
      Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation
      Schedule (ADOS) domain scores were examined using linear mixed effects models.
      Data for the 228 families studied were provided by the Autism Genetic Resource
      Exchange. Hypertension (P = 0.002), preeclampsia (P = 0.021) and generalized
      edema (P = 0.011) were associated with higher ADI-R communication scores.
      Hypertension (P = 0.011), albuminuria (P = 0.039) and generalized edema (P =
      0.009) were associated with higher ADI-R repetitive behaviors scores. Parent
      depression was associated with higher ADI-R repetitive behaviors scores (P =
      0.005), and parent anxiety with lower ADOS social/communication composite scores
      (P = 0.025). The associations between hypertension-related obstetric conditions
      and autistic severity warrant further investigation and raise intriguing
      questions regarding potential causal and modifying factors in autism.

PMID- 18324468
TI  - Brief report: pilot investigation of service receipt by young children with
      autistic spectrum disorders.
AB  - Whether children with autistic spectrum disorders (ASD) and their families are
      receiving recommended assessments and services is poorly known. This pilot study
      examined service receipt as reported by parents of young children with ASD (n =
      64) from four specialty centers in Canada. While almost all children had a speech
      and language assessment (94%), less than half had psychological (42%), or genetic
      (31%) testing. Speech and language (88%) and occupational (78%) therapies were
      the most frequently received treatments. Overall, certain findings did not
      correspond to recent recommended practice guidelines. Future studies should
      obtain more detailed information on assessments and treatments received from
      larger and more representative samples to better determine the quality of care
      received by families with children with ASD.

PMID- 18324469
TI  - Evaluation of a prevention intervention to reduce HIV Risk among Angolan
      soldiers.
AB  - We developed and evaluated a military-focused HIV prevention intervention to
      enhance HIV risk-reduction knowledge, motivation, and behaviors among Angolan
      soldiers. Twelve bases were randomly assigned to HIV prevention or control
      conditions, yielding 568 participants. HIV prevention participants received
      training in preventing HIV (4.5 days) and malaria (0.5 days). Control
      participants received the reverse. Monthly booster sessions were available after
      each intervention. We assessed participants at baseline, 3 and 6 months after the
      training. HIV prevention participants reported greater condom use and less
      unprotected anal sex at 3 months, as well as greater HIV-related knowledge and
      perceived vulnerability at 3 and 6 months. Within-group analyses showed HIV
      prevention participants increased condom use, reduced unprotected vaginal sex,
      and reduced numbers of partners at both follow-ups, while control participants
      improved on some outcomes at 3 months only. A military-focused HIV prevention
      intervention may increase HIV-related knowledge, motivation, and risk reduction
      among African soldiers.

PMID- 18324470
TI  - Rapid assessment of HIV risk behavior in drug using sex workers in three cities
      in South Africa.
AB  - A rapid assessment was undertaken with drug using commercial sex workers (CSWs)
      to investigate practices putting them at risk for contracting HIV. It included
      key informant (KI) (N = 67) and focus group (N = 10) interviews in locations with
      a high prevalence of drug use in Cape Town, Durban and Pretoria, South Africa.
      HIV testing of KIs was conducted. Cocaine, Ecstasy, heroin and methaqualone are
      used by CSWs prior to, during and after sex. Drugs enhance the sexual experience
      and prolong sex sessions. Interviews revealed inconsistent condom use among CSWs
      together with other risky sexual practices such as needle sharing. Among CSWs who
      agreed to HIV testing, 34% tested positive. Barriers to accessing drug treatment
      and HIV treatment and preventive services were identified. Interventions
      recognizing the role of drug abuse in HIV transmission should be prioritized, and
      issues of access to services, stigma and power relations must be considered.

PMID- 18324471
TI  - Molecular variability of Hop stunt viroid: identification of a unique variant
      with a tandem 15-nucleotide repeat from naturally infected plum tree.
AB  - For this study, 68 plum samples were collected from 12 provinces of China. Low
      molecular weight RNAs were extracted and used for dot-blot, reverse transcription
      polymerase chain reaction (RT-PCR), return-polyacrylamide gel electrophoresis,
      and biological indexing using cucumber. Results showed that 15 out of the 68 plum
      samples were positive for Hop stunt viroid (HSVd). Four positive samples were
      selected for cloning and sequence analysis. Results indicated that most HSVd
      sequences from the plum in China had 1-3 nucleotide changes from the closest HSVd
      in GenBank. In addition, the sample PB21 (cv. 'Friar') collected from Hebei
      province had one sequence with a 15-nt duplication (named HSVd D-15) at the
      244/245 position in the lower central region. By biological indexing, cucumber
      seedlings, an indicator plant for HSVd, were inoculated with RNAs directly
      extracted from the original plum source (PB21, cv. 'Friar'). Nucleotide
      sequencing analysis of the progeny showed that HSVd, but not HSVd-D15, was
      recovered from inoculated cucumbers. Although very unlikely, the possibility that
      this extra sequence was the result of a PCR artifact cannot be completely ruled
      out.

PMID- 18324472
TI  - Race and triple negative threats to breast cancer survival: a population-based
      study in Atlanta, GA.
AB  - BACKGROUND: Breast cancers with a triple negative tumor (TNT) subtype (as defined
      by lacking protein expression of estrogen receptor (ER), progesterone receptor
      (PR), and human epidermal growth factor receptor 2 (HER2)) preclude the use of
      available targeted therapies and may contribute to poor outcome and to the
      historically poorest survival observed among African-American (AA) women. This
      study examines association of the ER/PR/HER2 subtypes with race and breast cancer
      survival. METHODS: Breast tumors from a population-based cohort of 116 AA and 360
      white Atlanta women aged 20-54, diagnosed from 1990 to 1992 were centrally
      reviewed and tested by immunohistochemistry. Multivariate survival analyses
      within subtypes (TNT, ER-PR-HER2+, ER+/PR+HER2+, ER+/PR+HER2-) were conducted
      using weighted Cox regression and included socio-demographic, prognostic, and
      treatment factors. RESULTS: TNTs were more prevalent among young women and
      particularly among AA women (Odds Ratio [OR] = 1.9, 95% Confidence Interval [CI]
      1.2-2.9), adjusting for age, stage, grade, and poverty index. Overall mortality
      was higher for AA women (Hazard Ratio [HR] = 1.9, 95% CI, 1.5-2.5) and differed
      by subtypes (P < 0.001). Within the TNT subtype, racial differences in survival
      persisted, after additional adjustment for treatment and comorbidities (HR = 2.0,
      95% CI 1.0-3.7). TNTs were uniquely associated with high expression of p16, p53,
      and Cyclin E; and low Bcl-2 and Cyclin D1 expression. CONCLUSIONS: The high
      prevalence of TNTs among younger women and particularly younger AA women, along
      with unique protein expression patterns and poorer survival, suggests varying
      gene-environment etiologies with respect to age and race/ethnicity and a need for
      effective therapies.

PMID- 18324474
TI  - Microneedle-based drug delivery: studies on delivery parameters and
      biocompatibility.
AB  - There is a significant interest in the application of microneedles in intradermal
      drug delivery systems. Previous studies have demonstrated that skin permeation of
      drugs can be increased by orders of magnitude with microneedle insertion. In this
      study, emphasis is placed on the development of low cost, painless intradermal
      microneedle systems that can enhance the percutaneous drug permeation.
      Microneedles of octagonal pyramidal shape with the length of 150 mum were
      employed, and the capabilities of skin permeation enhancement under different
      delivery conditions were examined. The delivery parameters taken into account
      included the insertion time and the area of insertion. It was found that when
      solid microneedle arrays of 150 mum in length were pierced into human dermatomed
      skin for 5 to 60 s, microconduits with the depth of 50 to 80 mum were created to
      facilitate the percutaneous permeation of drugs. In percutaneous tests, it was
      demonstrated that the permeability coefficient of calcein (MW = 622.55) was
      significantly increased by 10(4) to 10(5) times compared to that on intact skin.
      In terms of biocompatibility, biological evaluation indicated a broad spectrum of
      safety for the microneedle system. These results suggest that the octagonal
      pyramidal microneedles can be an effective tool in developing novel intradermal
      drug delivery system.

PMID- 18324475
TI  - The pituitary-adrenal axis and body composition.
AB  - The activity of the pituitary-adrenal axis can profoundly impact on body
      composition. This is dramatically seen in Cushing's syndrome (CS) but changes in
      body composition are also implicated in depression and alcoholic pseudocushing's.
      The pathophysiological mechanisms underlying these changes remain poorly
      understood. Changes to body composition in CS include increased fat mass,
      decreased bone mass, thinning of the skin and reduced lean mass. Why these
      tissues are affected so dramatically is unclear. Additionally, the change in body
      composition between individuals varies considerably for reasons which are only
      now becoming evident. This paper reviews the phenotypic changes with altered
      pituitary-adrenal axis activity and discusses the mechanisms involved. The
      primary focus is on adipose, bone, muscle and skin since the most dramatic
      changes are seen in these tissues.

PMID- 18324476
TI  - Flex: a new computerized system for mechanical ventilation.
AB  - OBJECTIVE: To describe and evaluate a new weaning and decision support system for
      mechanical ventilation. BACKGROUND: FLEX is a computerized weaning and decision
      support system for mechanical ventilation that unlike previous rule-based systems
      derives many of its rules on the basis of the conditions of individual patients.
      This system can be used in a wide range of ventilatory modes as well as automatic
      control of weaning. It incorporates the features of the patented ventilatory mode
      known as Adaptive Support Ventilation (ASV) along with other new features for
      control of weaning, and control of patient's oxygenation by adjustment of PEEP
      and the fraction of inspired oxygen. METHODS: Ventilator data was collected for
      10 patients in medical/surgical ICU at baseline and about 24 hours later.
      Required data fields for each patient for these two time points were also entered
      into the FLEX program. Comparison of clinical data and FLEX recommendations were
      made with regard to minute ventilation, alarms, weaning institution and other
      variables. RESULTS: At baseline, 7 patients were being treated with AC, the
      remainder with IMV/PS. There was good agreement between the measured and
      recommended minute ventilations; variances were seen in some patients being
      treated with permissive hypercapnea and those with evidence of high oxygen needs
      or other metabolic derangements. At 24 hours, there was improved correlation
      between measured minute ventilation and that recommended by FLEX, suggesting that
      clinical adjustments were in-line with Flex recommendations over time.
      Furthermore, FLEX made recommendations with regard to FIO(2) and PEEP that would
      potentially diminish the risk of oxygen toxicity, hypoxemia, and barotrauma in
      selected patients. FLEX has also been implemented as a closed loop system in an
      initial set up. CONCLUSION: A new weaning and decision support system for
      mechanical ventilation is presented. The recommendations made by the system were
      found to be in line with clinical determinations. Further refinements in the FLEX
      predictions can be easily made by including inputs which represent permissive
      hypercapnea or increased metabolic demand for selected patients.

PMID- 18324477
TI  - Video monitoring of neovessel occlusion induced by photodynamic therapy with
      verteporfin (Visudyne), in the CAM model.
AB  - The aim of the present study was to monitor photodynamic angioocclusion with
      verteporfin in capillaries. Details of this process were recorded under a
      microscope in real-time using a high-sensitivity video camera. A procedure was
      developed based on intravenous (i.v.) injection of a light-activated drug,
      Visudyne, into the chorioallantoic membrane (CAM) of a 12-day-old chicken embryo.
      The effect of light activation was probed after 24 h by i.v. injection of a
      fluorescent dye (FITC dextran), and analysis of its fluorescence distribution.
      The angioocclusive effect was graded based on the size of the occluded vessels,
      and these results were compared with clinical observations. The time-resolved
      thrombus formation taking place in a fraction of the field of view was video
      recorded using a Peltier-cooled CCD camera. This vessel occlusion in the CAM
      model was reproducible and, in many ways, similar to that observed in the
      clinical use of verteporfin. The real-time video recording permitted the
      monitoring of platelet aggregation and revealed size-selective vascular closure
      as well as some degree of vasoconstriction. Platelets accumulated at
      intravascular junctions within seconds after verteporfin light activation, and
      capillaries were found to be closed 15 min later at the applied conditions.
      Larger-diameter vessels remained patent. Repetition of these data with a much
      more sensitive camera revealed occlusion of the treated area after 5 min with
      doses of verteporfin and light similar to those used clinically. Consequently,
      newly developed light-activated drugs can now be studied under clinically
      relevant conditions.

PMID- 18324478
TI  - VEGF, COX-2, and PCNA expression in renal cell carcinoma subtypes and their
      prognostic value.
AB  - OBJECTIVE: To evaluate the prognostic value of new markers such as VEGF (vascular
      endothelial growth factor), COX-2 (cyclooxygenase-2), and PCNA (proliferating
      cell nuclear antigen) and review their differences in expression by histological
      subtype in patients with renal cell carcinoma (RCC). METHODS: About 99 patients
      who underwent radical (n = 79) or partial nephrectomy (n = 20) were included in
      this study. Histopathological specimens from the subjects were retrospectively
      analyzed immunohistochemically for the presence of VEGF, COX-2, or PCNA. RESULTS:
      Mean staining ratios for VEGF, COX-2, and PCNA were 16.5, 16.8, and 31%,
      respectively. Correlations were evaluated among these three prognostic factors.
      There was no correlation between PCNA and VEGF (P = .068), but there were
      significant correlations between COX-2 and both PCNA and VEGF (P = .005 and P =
      .000, respectively). A significant correlation was found between the expression
      of VEGF and both pathologic stage and vascular invasion (P = .018 and P = .025,
      respectively). In addition, patients with conventional RCC had significantly
      lower VEGF and COX-2 levels than those with papillary RCC (P < .012).
      CONCLUSIONS: It is obvious that prognostic factors such as VEGF, COX-2, and PCNA
      may vary depending on histological subtype. The level of expression of these
      factors together with histological subtype may provide valuable predictive
      information about the outcome of treatment.

PMID- 18324479
TI  - Improving quality of life using compound mind-body therapies: evaluation of a
      course intervention with body movement and breath therapy, guided imagery, chakra
      experiencing and mindfulness meditation.
AB  - OBJECTIVE: Assess changes in quality of life and in sense of coherence (SOC),
      after an intervention involving a self-development course using mind-body
      medicine (MBM) activities. DESIGN: A questionnaire study using a health-related
      quality of life (HRQOL) instrument, the SWEDQUAL, with 13 subscales and scores
      ranging from 0 to 100, combined with the SOC-13 scale, healthcare utilisation,
      medication and sick listing data. SETTING: A training centre for MBM. Eligible
      course attendants (study group, SG, n = 83) assessed their HRQOL before and 6
      months after a 1-week course. A control group (CG) of individuals who had
      previously attended the course (n = 69), matched for age, sex and length of
      course time to the SG, also made assessments. MAIN OUTCOME: Changes in HRQOL and
      SOC in SG and CG. RESULTS: Of the 13 HRQOL subscales, eight showed clinically
      significant improvement in the SG (>9%, p < 0.01), namely, General health
      perceptions (9%), Emotional well-being [negative (45%) and positive (26%)],
      Cognitive functioning (24%), Sleep (15%), Pain (10%), Role limitation due to
      emotional health (22%) and Family functioning (16%). Sexual, marital and physical
      function and role in the SG as well as all CG scores were similar to average
      population values. The assessed SOC also improved in the SG after intervention (p
      < 0.01), challenging previous statements of 'the stableness of SOC'. Use of
      psychotropic medication was slightly reduced in the younger aged SG participants
      after intervention. CONCLUSIONS: This group of men and women (SG), starting from
      a clinically significant low health assessment, had improved their HRQOL and SOC
      after the course intervention.

PMID- 18324480
TI  - Effects of dehydroepiandrosterone on aldosterone release in rat zona glomerulosa
      cells.
AB  - The present study was to investigate the effects and action mechanisms of
      dehydroepiandrosterone (DHEA) on steroidogenesis in rat adrenal zona glomerulosa
      cells (ZG). ZG cells were incubated with DHEA in the presence or absence of
      angiotensin II (AngII), a high concentration of potassium, 8-Br-cAMP, forskolin,
      25-OH-cholesterol, pregnenolone, progesterone, deoxycorticosterone,
      corticosterone, A23187, or cyclopiazonic acid (CPA) at 37 degrees C for 1 h. The
      concentration of aldosterone or pregnenolone in the culture medium was then
      measured by radioimmunoassay (RIA). The cells were used to determine the cellular
      cAMP content. The data demonstrated that: (1) DHEA inhibited AngII-, high
      concentration of KCl-, forskolin-, 8-Br-cAMP-, 25-OH-cholesterol-, pregnenolone-,
      progesterone-, deoxycorticosterone-, corticosterone-, A23187-, or CPA-stimulated
      aldosterone release; (2) DHEA increased 25-OH-cholesterol-stimulated pregnenolone
      release but not when 25-OH-cholesterol was combined with trilostane; (3) DHEA
      noncompetitively inhibited aldosterone synthase but showed uncompetitive
      inhibition of P450scc. These results suggest that DHEA acts directly on rat ZG
      cells to diminish aldosterone secretion by inhibition of a post-cAMP pathway or
      by acting on intracellular Ca2+ mobilization. In addition it affects the function
      of post-P450scc steroidogenic enzymes.

PMID- 18324481
TI  - Molecular mechanisms of autoimmunity.
AB  - Autoimmunity is mediated by a variety of mechanisms, molecular and cellular
      events, and responses. Predisposition to a given autoimmune response requires the
      requisite allele(s) that controls antigen presentation by antigen-presenting
      cells for T cell recognition. Some autoimmune responses emerge following
      infection by a pathogen, whose protein(s) possess structural similarities in some
      of its epitopes to regions on proteins of the host. Thus, antibodies evoked
      against a pathogen might cross-react with a self-protein and act as
      autoantibodies, and the involved autoantigen then provides a source for
      persistent stimulation. Proteins to which the immune system is ordinarily self
      tolerant might, if altered, elicit autoimmune responses. Ways in which self
      proteins can be altered include mutations and altered expression,
      posttranslational modification, covalent modifications, denaturation, native
      disorder or misfolding. Sequestered proteins normally sheltered from immune
      recognition become immunogenic and targets of immune effector functions, once
      exposed to the immune system. Other alterations can occur because of disruption
      in the levels or activity of regulatory proteins. These include certain alleles
      of the cytotoxic T lymphocyte-associated antigen-4 gene (possibly a nonspecific
      exacerbating molecule of disease risk in several autoimmune diseases), the
      lymphoid protein tyrosine phosphatase nonreceptor type 22 gene (associated with
      type 1 diabetes and other autoimmune diseases), TNF-alpha (involved in chronic
      inflammation, autoimmunity and malignancies) and the FOXP3 gene (expressed by
      CD4+C25+ regulatory T cells), whose mutations can cause immune dysregulation,
      polyendocrinopathy and X-linked inheritance syndromes of systemic autoimmunity.
      An autoimmune response can also arise from natural antibodies or autoantibodies
      that occur independently of known immunization and are able to bind to microbial
      antigens, altered proteins as well as self-antigens. Natural autoantibodies
      possess in general a low intrinsic affinity for antigen, but can function as
      templates for the generation of pathogenic autoantibodies, that emerge through a
      process of clonal selection entailing somatic hypermutation and class switch DNA
      recombination, as driven by antigen.

PMID- 18324482
TI  - Expression of AIRE in thymocytes and peripheral lymphocytes.
AB  - Autoimmune regulator (AIRE) is a transcription factor expressed in the thymic
      medullary epithelial cells (MECs). MECs have been suggested to contribute to
      tolerance induction by presenting tissue specific antigens to T cells that react
      to these antigens. AIRE expression in cells other than MECs has not been studied
      extensively. Here we report four-color flow cytometric and quantitative real-time
      PCR studies on the expression of AIRE in the lymphoid cells in the thymus and
      periphery. In the thymus AIRE was expressed in B cells and CD4+CD8+ double
      positive cells at a low level. In the peripheral blood AIRE was expressed in B
      cells but not in T cells, and also expressed in CD14+ dendritic cells
      (DCs)/macrophages and granulocytes at higher levels. AIRE mRNA was expressed
      higher in B cells than in T cells. Further study is warranted to define the
      functional role of the AIRE expressed in the lymphoid cells.

PMID- 18324483
TI  - Ictus and antiphospholipid syndrome: how much is enough?
AB  - Herein we report the case of a patient with antiphospholipid Syndrome (APS) and
      an ischemic stroke suffered while he was anticoagulated, and we discuss the
      usefulness of magnetic resonance angiography in the early diagnosis of such a
      complication. We also attempt to emphasize the great value of an individual risk
      evaluation when warfarin therapy is introduced. In fact, our case supports the
      importance of high-intensity anticoagulation in patients with multiple thrombotic
      recurrences, and the exceptional value that strict anticoagulation control has in
      this kind of patients.

PMID- 18324484
TI  - Detection and immunochemical characterization of glutamic acid decarboxylase
      autoantibodies in patients with autoimmune diabetes mellitus.
AB  - Since GAD65 undergoes post-translational processing and targeting to subcellular
      compartments and membranes, it may exhibit different immunochemical properties in
      the cell context compared with the soluble protein expressed in the cell-free
      eukaryotic system used in the reference method for GADA assessment (radioligand
      binding assay (RBA)). In the present work, we detected and characterized GADA in
      72 sera from patients with type 1 diabetes mellitus (DM) and 14 sera from adult
      onset diabetes patients using analytical systems in which GAD65 is expressed in a
      cellular context: confocal indirect immunofluorescence (IIF) and electron
      microscopy after immunogold labeling on monolayers of transfected Chinese hamster
      ovary (CHO) cells, and immunoprecipitation (IP) of metabolically labeled GAD65.
      Eighteen serum samples, 16 from type 1 diabetes patients and two from adult-onset
      diabetes patients, were positive by confocal IIF but scored negative by RBA. All
      of these 18 sera immunoprecipitated a 65 kDa protein, supporting the existence of
      the GADA marker in such patients. It may be concluded that GADA negativity by the
      conventional RBA method using the soluble antigen, as well as negativity for
      other common markers measured by similar methods, is not enough to rule out the
      existence of the specific autoimmune component in childhood or adult-onset
      diabetes. Other analytical methods based in a more physiological presentation of
      the autoantigen structure, as confocal IIF and IP, bring an extra support to
      assess the complete repertoire of specific autoantibodies to native-like and
      membrane-bound, or denatured, beta-cell antigens.

PMID- 18324485
TI  - The inflammatory Th 17 subset in immunity against self and non-self antigens.
AB  - T helper cells (Th cells) are traditionally thought to differentiate into Th1 and
      Th2 subsets based on their cytokine profiles. Recently, a subset of interleukin
      (IL)-17-producing cells (Th17 cells) which develop and function in a distinct way
      from Th1 or Th2 cells has been identified. Th17 cells have been shown to play a
      crucial role in the induction of autoimmune tissue injuries, inflammation and
      infection. Studies on Th17 subset and its relevant issues offered potential
      therapeutic targets for patients with autoimmune diseases, cancer, infection and
      transplant, which may have significant impacts in the prevention and/or treatment
      of immunity-related diseases in clinics.

PMID- 18324486
TI  - Identification of apoptotic proteins in thyroid gland from patients with Graves'
      disease and Hashimoto's thyroiditis.
AB  - Apoptosis, i.e. natural programmed cell death, is a physiological phenomenon
      indispensable for normal functioning of the organism. The signal to apoptosis can
      be started practically in any cell. Disturbances in the apoptosis regulation
      determine the essential link of the pathogenesis of many diseases, including
      autoimmune thyroid disorders. The aim of the study was to assess the expression
      of Fas/FasL and caspase eight in the tissues of the thyroid gland in patients
      with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's
      thyroiditis (HT). The analysis of Fas/FasL expression was performed by western
      blot and immunohistochemical investigation with DAB-visualization and Mayer's
      hematoxylin staining. Caspase-8 expression in thyroid follicular cells was
      assayed by western blot method. Identification of the proapoptotic proteins FasL
      and Fas exhibited their pronounced expression in the thyroid tissue in GD
      patients (++; ++) and HT (+++; +++) as compared to the NTNG group (0/+; 0/+).
      Among the study groups, the expression of caspase-8 was revealed in band 55 kDa
      from patients with autoimmune thyroid diseases. In GD patients, the percentage of
      thyrocytes with FasL expression correlated positively with TRAb (R = 0.58, p <
      0.02). However, no such correlations were noted in HT or non-toxic multinodular
      goiter. There were no significant correlations between thyroid hormones and the
      percentage of thyrocytes with Fas and FasL expression. In conclusion, our
      findings suggest that the changes in the expression of apoptotic molecules on the
      surface of T lymphocytes and thyroid follicular cells in patients with autoimmune
      thyroid disorders reflect their substantial involvement in the pathogenesis of GD
      and HT. In addition, analysis of Fas/FasL and caspase-8 expression in thyroid
      tissue may indicate the disease activity and immunological phenotype.

PMID- 18324487
TI  - Association between parity and autoimmune thyroiditis in a general female
      population.
AB  - BACKGROUND: Autoimmune thyroid disease (AIT) is more common in females than in
      males. Furthermore, it is well documented that the risk of thyroid autoimmunity
      increases during pregnancy and in the postpartum period. The objective of the
      present study was to analyse the association between parity and AIT by using
      ultrasound and serological data. METHODS: The study population included 2156
      women, aged 20-79 years. Serum thyroperoxidase antibodies (anti-TPO) and
      thyrotropin levels were measured and thyroid ultrasonography was performed. AIT
      was defined according to the combined presence of a hypoechogenic thyroid pattern
      and positive anti-TPO levels (>200 IU/ml). Odds ratios (OR) and 95% confidence
      intervals (CI) were calculated. RESULTS: The analyses revealed an association
      between parity and AIT. Women with at least one pregnancy had increased odds for
      AIT (OR 4.6 [95%-CI 1.4-15.1], p < 0.05) compared to women who have never been
      pregnant. Similar results were observed using hypoechogenic thyroid pattern (OR
      1.7 [95%-CI 1.0-2.9], p < 0.05) and positive anti-TPO levels (OR 1.8 [95%-CI 1.0
      3.3], p = 0.05) as separate dependent variables or using number of births as
      alternate independent variable. CONCLUSION: In this female population we found an
      association between parity and AIT and conclude that parity appears to be a
      potential risk factor for AIT.

PMID- 18324488
TI  - Renal impairment and amphotericin B formulations in patients with invasive fungal
      infections.
AB  - A systematic review was performed to examine renal function in patients with
      invasive fungal infections, comparing the nephrotoxicity caused by conventional
      amphotericin B deoxycholate (c-AmB) with that induced by the use of lipid-based
      amphotericin B formulations. The analysis considered all comparative studies
      published in the literature between January 1996 and May 2007. The outcome data
      reviewed herein focused on renal toxicity as measured by serum creatinine (S-Cr)
      and the doubling or the mean difference in S-Cr levels from baseline to the end
      of therapy or the need for dialysis. We found that AmB lipid complex (ABLC),
      liposomal AmB (L-AmB) and AmB colloidal dispersion (ABCD) were significantly less
      nephrotoxic than c-AmB in all reported studies. ABLC and L-AmB caused low and
      comparable nephrotoxicity in nine studies. In one randomized study, L-AmB was
      significantly less nephrotoxic than ABLC. No studies compared ABCD nephrotoxicity
      to the other lipid formulations. Based on our review we conclude that lipid
      formulations of amphotericin B are an important strategy to preserve renal
      function and improve survival in critically ill patients who require treatment
      for systemic fungal infections.

PMID- 18324489
TI  - Experimental paracoccidioidomycosis: alternative therapy with ajoene, compound
      from Allium sativum, associated with sulfamethoxazole/trimethoprim.
AB  - Ajoene has been described as an antithrombotic, anti-tumour, antifungal,
      antiparasitic and antibacterial agent. This study deals with the efficacy of
      ajoene to treat mice intratracheally infected with Paracoccidioides brasiliensis.
      The results indicate that ajoene therapy is effective in association with
      antifungal drugs (sulfametoxazol/trimethoprim), showing a positive additive
      effect. Ajoene-treated mice developed Th1-type cytokine responses producing
      higher levels of IFN-gamma and IL-12 when compared to the infected but untreated
      members of the control group. Antifungal activity of ajoene involves a direct
      effect on fungi and a protective pro-inflammatory immune response. Reduction of
      fungal load is additive to chemotherapy and therefore the combined treatment is
      mostly effective against experimental paracoccidioidomycosis.

PMID- 18324490
TI  - Comparison of E-Test, disk diffusion and a modified CLSI broth microdilution (M
      38-A) method for in vitro testing of itraconazole, fluconazole and voriconazole
      against dermatophytes.
AB  - We compared two agar-based methods, the E-test and the disk diffusion method with
      the Clinical Laboratory Standards Institute (CLSI) reference broth microdilution
      method (CLSI M38-A; MD). Forty six dermatophytes strains including 30
      Trichophyton mentagrophytes, 8 T. rubrum and 8 M. gypseum were tested against
      three antifungal agents, i.e., fluconazole (FLC), itraconazole (ITC) and
      voriconazole (VRC). The level of agreement between the E-test and MD (+/-2
      dilutions) was 45.6% for fluconazole, 19.5% for itraconazole and 52.1% for
      voriconazole. The results obtained with disk diffusion had low correlation with
      the results obtained by the CLSI broth microdilution reference method with
      azoles.

PMID- 18324491
TI  - Upregulation of glyoxylate cycle genes upon Paracoccidioides brasiliensis
      internalization by murine macrophages and in vitro nutritional stress condition.
AB  - Paracoccidioides brasiliensis, the etiologic agent of paracoccidioidomycosis, is
      a facultative intracellular human pathogen that can persist within macrophage
      phagolysosomes, indicating that the fungus has evolved defense mechanisms in
      order to survive under nutritionally poor environments. The analysis of P.
      brasiliensis transcriptome revealed several virulence factor orthologs of other
      microorganisms, including the glyoxylate cycle genes. This cycle allows the
      utilization of two-carbon (C2) compounds as carbon source in gluconeogenesis.
      Semiquantitative RT-PCR analyses revealed that these genes were upregulated when
      P. brasiliensis was recovered from murine macrophages, without any additional in
      vitro growth. The induction of this cycle, in response to macrophage
      microenvironments, was shown to be coordinated with the upregulation of the
      gluconeogenic phosphoenolpyruvate carboxykinase gene. In addition, assays
      employing RNA extracted from P. brasiliensis grown in a medium with acetate
      instead of glucose also showed increased levels of glyoxylate cycle transcripts.
      Our main results suggest that P. brasiliensis uses the glyoxylate cycle as an
      important adaptive metabolic pathway.

PMID- 18324492
TI  - Over-expression of genes coding for proline oxidase, riboflavin kinase,
      cytochrome c oxidase and an MFS transporter induced by acriflavin in Trichophyton
      rubrum.
AB  - Acriflavin (3,6-acridinediamine) and other acridine derivatives act in both
      prokaryotic and eukaryotic cells at the level of DNA-coiling enzymes
      (topoisomerases) causing the stabilization of the enzyme-DNA cleavable complex.
      In order to better understand the mode of action of acriflavin, Differential
      Display RT-PCR was used to isolate transcripts specifically over-expressed during
      exposure of Trichophyton rubrum mycelia to this drug. Five transcripts, whose
      differential expressions were confirmed by Northern blotting, revealed genes not
      previously described in this dermatophyte. Functional grouping identified
      putative enzymes possibly involved in the mitochondrial respiratory electron
      transport chain and in iron transport. These results may be relevant to our
      understanding of the molecular events involved in the stress response of T.
      rubrum to acriflavin.

PMID- 18324493
TI  - Molecular epidemiology and antifungal susceptibility patterns of Sporothrix
      schenckii isolates from a cat-transmitted epidemic of sporotrichosis in Rio de
      Janeiro, Brazil.
AB  - Since 1998 a cat-transmitted epidemic of sporotrichosis has been observed in Rio
      de Janeiro (RJ), Brazil. Besides the lymphocutaneous and fixed forms, other
      presentations, such as disseminated cutaneous and mucosal involvement, as well as
      for the first time, erythema nodosum and erythema multiforme have been reported
      associated with sporotrichosis. This study investigates the phenotypes and
      genotypes of Sporothrix schenckii isolates recovered from different clinical
      forms of the disease noted as part of this epidemic. A total of 88 isolates
      recovered from 59 cases associated with the epidemic and 29 controls (from cases
      in other Brazilian regions and Spain) were included in this study. In vitro
      susceptibility testing was conducted as part of the phenotypic analysis, while
      the genotypic analysis involved a DNA fingerprinting method with primer M13 and
      ribosomal DNA sequencing of the internal transcribed spacer (ITS). MIC values of
      amphotericin B, itraconazole, posaconazole, ravuconazole, and terbinafine were
      found to be significantly lower (P<0.01) for isolates associated with the
      epidemic than for control strains. No differences in MIC values were observed
      related to clinical forms of the infection. Fingerprinting analysis showed that
      RJ epidemic strains were genetically related. Although nine subtypes were found,
      they were not associated with specific clinical forms. Similar results were
      obtained with the ITS sequence analysis. These data suggest that the strains
      isolated from the epidemic cases of sporotrichosis in RJ all originated from a
      common source.

PMID- 18324494
TI  - Spleen deposition of Cryptococcus neoformans capsular glucuronoxylomannan in
      rodents occurs in red pulp macrophages and not marginal zone macrophages
      expressing the C-type lectin SIGN-R1.
AB  - The fate of microbial polysaccharides in host tissues is an important
      consideration because these compounds are often immune modulators. Splenic
      marginal zone macrophages that express the C-type lectin receptor SIGN-R1, take
      up neutral polysaccharides such as dextran and the capsular polysaccharide of
      Streptococcus pneumoniae. Given that the major component of Cryptococcus
      neoformans capsular polysaccharide, glucuronoxylomannan (GXM), localizes in the
      spleen when injected intravenously, we investigated whether GXM uptake was
      mediated by splenic macrophages expressing the SIGN-R1 receptor in mice. No
      significant differences in the amount and location of GXM deposition were
      detected in the spleens of mice treated with a SIGN-R1 blocking antibody when
      compared to controls. Similarly, a blocking antibody to Dectin-1, a co-receptor
      of -SIGN-R1, had no effects on GXM distribution within the spleen. Histological
      examination of spleens from mice and rats injected with FITC-Dextran and GXM
      revealed no significant co-localization, with Dextran and GXM being found in
      marginal and red pulp macrophages, respectively. Hence we conclude that GXM was
      not deposited in marginal zone macrophages. However, GXM deposition was found in
      the red pulp. These results indicate that there is a selective localization of
      these polysaccharides to different receptors such as SIGN-R1 for FITC dextran in
      marginal zone and a to-be-identified receptor selectively expressed by red pulp
      macrophages for GXM.

PMID- 18324495
TI  - A rare case of chromoblastomycosis in a renal transplant recipient caused by a
      non-sporulating species of Rhytidhysteron.
AB  - We report a rare case of chromoblastomycosis caused by a non-sporulating species
      of Rhytidhysteron (Order Patellariales, Ascomycota) which was identified by
      molecular methods. The patient was a post-renal transplant recipient male aged 50
      years and a resident of Delhi. The diagnosis was made by direct microscopy,
      histopathology and isolation of multiple colonies of the dematiaceous mould in
      pure culture. The samples used to recover the organism were obtained from a
      biopsy of one of the lesions occurring on his left foot and extending to the shin
      and thigh. The lesions comprised necrotic granulation tissue with indurated and
      thickened margins. After 2 weeks of therapy with itraconazole, 100 mg twice
      daily, the lesions partially retracted. However, the patient developed
      complications of acute abdominal pain with respiratory distress, necessitating
      admission to a tertiary-care hospital where he died due to multiple organ failure
      within 48 h. All attempts to induce sporulation of the fungal isolate on various
      mycological culture media were unsuccessful. Thereafter, sequencing of the 18S
      rRNA gene of the isolate and its comparison with GenBank database revealed that
      the fungus belonged to the genus Rhytidhysteron. As far as we are aware, this is
      the first case of human infection caused by a fungus of the Order Patellariales.
      The case underlines the relevance of molecular techniques as valuable tools for
      identification of non-sporulating opportunistic pathogenic fungi.

PMID- 18324496
TI  - Fournier's gangrene due to Candida glabrata.
AB  - Fournier's gangrene is a rare and serious event. Usual pathogens are bacteria of
      the skin and the digestive tract. Candida species are exceptionally involved,
      mostly Candida albicans. We report a patient with non-C. albicans Candida sp.
      Fournier's gangrene who survived with an appropriate antifungal therapy. Yeasts
      should be considered as emerging pathogens in pelvic infections due to the
      increase in long-term immunocompromised patients.

PMID- 18324497
TI  - Transuterine transmission of Aspergillus terreus in a case of disseminated canine
      aspergillosis.
AB  - Aspergillus terreus was isolated from the organs of a German Shepherd pup removed
      from the bitch by cesarean intervention. In the following days, the bitch
      developed signs of canine disseminated aspergillosis and was euthanized. The
      fungus was isolated from a necrotic lesion in the uterus and other organs. To the
      best of our knowledge, this is the first report of the transuterine transmission
      of A. terreus during a case of canine disseminated aspergillosis.

PMID- 18324498
TI  - Extensive chromoblastomycosis caused by Fonsecaea pedrosoi successfully treated
      with a combination of amphotericin B and itraconazole.
AB  - Chromoblastomycosis is a chronic infection caused by dematiaceous (dark-colored)
      fungi which affect the skin and subcutaneous tissues, and is characterized by a
      wide variety of clinical and dermatological features including papillomatous,
      verrucous and vegetating lesions. Although it has been described world-wide, most
      cases originate in tropical and sub-tropical areas. In general, present
      treatments of the disease are unsatisfactory as one of the most common etiologic
      agents, Fonsecaea pedrosoi is difficult to manage from a therapeutic point of
      view. We report a case of extensive chromoblastomycosis of 22 years duration
      caused by F. pedrosoi and review the clinical course, diagnosis and management of
      this disease.

PMID- 18324499
TI  - Amphotericin B-deoxycholate overdose due to administration error in pediatric
      patients.
AB  - Due to the similarity of their generic names, the use of amphotericin B
      deoxycholate and liposomal amphotericin B could cause confusion in daily
      practice. We report two cases of amphotericin B-deoxycholate overdose in infants
      due to administration errors which raises the issue that the use of this
      antifungal agent should be questioned because of its severe side effects.

PMID- 18324500
TI  - Deactivation of the dimorphic fungi Histoplasma capsulatum, Blastomyces
      dermatitidis and Coccidioides immitis using hydrogen peroxide vapor.
AB  - Hydrogen peroxide vapour (HPV) has been proposed as an alternative to
      formaldehyde fumigation for the decontamination of biosafety level (BSL) III
      laboratories. The aim of this study was to evaluate the efficacy of HPV against
      the dimorphic fungi Histoplasma capsulatum, Blastomyces dermatitidis and
      Coccidioides immitis. Working inside a class II biological safety cabinet (BSC)
      within a BSL III laboratory, inocula containing approximately 5-log(10) cfu/ml
      from the mould form of each organism suspended in RPMI medium were deposited on
      stainless steel discs and allowed to air dry. The organisms were exposed to HPV
      inside a BSC using a BIOQUELL ClarusS HPV generator. In three replicate
      experiments, individual discs were transferred into liquid media at timed
      intervals during a 105 minute HPV exposure period. Control- and HPV-exposed discs
      were incubated in RPMI media at 30 degrees C for 6 weeks to determine if any
      viable organisms remained. Positive cultures were confirmed using specific
      nucleic acid hybridization probes. Results indicate that H. capsulatum, B.
      dermatitidis and C. immitis were killed within 30 minutes of HPV exposure.

PMID- 18324501
TI  - Gastro-oesophageal reflux disease redefined: Implications for primary care.

PMID- 18324502
TI  - Pulse oximetry in general practice: how would a pulse oximeter influence patient
      management?
AB  - The pulse oximeter is a vital piece of equipment in secondary care for the non
      invasive monitoring of oxygen saturation. With the increasing affordability of
      the oximeter and recognition of its clinical applications, there is an increasing
      interest in its role in primary care. The decision was made that a systematic
      review was not feasible due to the lack of data concerning the influence of pulse
      oximetry on patient management and on the extent of oximetry use in the general
      practice setting. In this article, a selection of studies is presented looking
      into its clinical use and limitations. The role and potential of the oximeter as
      a screening tool and aid in the assessment of hypoxia in a variety of clinical
      situations in primary care is discussed.

PMID- 18324503
TI  - Can elbow-extension test be used as an alternative to radiographs in primary
      care?
AB  - OBJECTIVE: To evaluate the ability of elbow extension, with the patient in a
      supine position, as a diagnostic test of an insignificant injury, with the
      purpose of avoiding unnecessary radiographs. METHODS: Seventy patients suffering
      from an acute elbow injury were examined at the accident and emergency
      department. Inability to fully actively extend the elbow in a supine position was
      defined as a positive diagnostic test. Radiographs were interpreted by a
      consultant radiologist, blinded to all clinical examination results. Sensitivity,
      specificity, positive and negative predictive values, and positive and negative
      likelihood ratios along with their 95% confidence intervals were calculated for
      the elbow-extension test. RESULTS: Forty out of 70 patients had a positive test.
      Elbow fracture or dislocation was identified radiographically in 22 patients with
      positive test (sensitivity 92%). Two out of 30 (with negative test) had a
      hairline radial head fracture, which was found on radiographs (specificity 61%).
      CONCLUSION: Elbow extension as a diagnostic test in a primary care setting can
      predict severe elbow injuries and can be safely used in practices with no
      radiology facilities.

PMID- 18324504
TI  - Referral patterns between the child health service, general practitioners, and
      secondary healthcare: a prospective descriptive study in the Netherlands.
AB  - BACKGROUND: In the Netherlands, preventive child health service (CHS) screening
      plays an important role in the early detection of congenital, developmental,
      physical, and mental disorders. OBJECTIVE: To obtain insight into the referral
      patterns of children from CHS to general practitioners and from general
      practitioners to medical specialists. METHODS: Prospective study over 6 months in
      a semi-urban area in the Netherlands. All correspondence from the participating
      doctors was sticker marked and, after each contact, a registration card was sent
      to a central secretariat. The referral stream between general practitioners and
      specialists or allied health professionals was extracted from a central database.
      The general practitioners and the participating paediatricians were asked to
      complete a questionnaire about the quality and necessity of the referral.
      RESULTS: Out of an estimated 2600 examinations, 45 children were referred to
      their general practitioners for further examination. The problems of eight
      children were settled by the GP, 10 children were referred to allied health
      professionals, and 24 children were referred to specialists. The median time span
      of showing up at the GP's office was 6.5 days. Sixteen per cent showed up long
      after having been referred by the CHS. The parents of three children did not
      comply. Of the 397 referrals from GPs to medical specialists and allied health
      professionals, 8.5% were initiated by the CHS. CONCLUSION: The amount of
      referrals from the CHS to GPs and of referrals from GPs to medical specialists
      and allied health professionals initiated by the CHS is low in terms of absolute
      percentages. Most referrals by the CHS were considered useful.

PMID- 18324505
TI  - Consultation charges in Ireland deter a large proportion of patients from seeing
      the GP: results of a cross-sectional survey.
AB  - OBJECTIVE: To estimate the effect of a consultation charge on the health-seeking
      behaviour of patients. METHODS: Cross-sectional survey of patients carried out in
      Northern Ireland, where services are free at the point of delivery, and the
      Republic of Ireland, where 70% of the population are charged a consultation fee
      to see the general practitioner (GP). RESULTS: There were 11 870 respondents to
      the survey (response rate 52%). In the Republic of Ireland, 18.9% of patients
      (4.4% of non-paying patients and 26.3% of paying patients) had a medical problem
      in the previous year but had not consulted the doctor because of cost; this
      compares with only 1.8% of patients in Northern Ireland. Because those in the
      Republic of Ireland on low income are entitled to free care, the effects of the
      consultation charge were most marked in the middle of the income distribution,
      with such patients being over four times as likely to have been deterred as those
      in the most affluent group. However, amongst paying patients, it was the poorest
      and those with the worst health who were most affected. Compared to the most
      affluent patients and those without depression, the likelihood of not having seen
      the GP due to cost was 6.75 (95% confidence interval [CI] 3.79, 11.09) for the
      poorest patients and 2.01 (95% CI 1.53, 2.52) for those with depression.
      CONCLUSION: Even in countries with exemptions for the poor and more vulnerable, a
      consultation charge can deter a large proportion of poorer and less healthy
      patients from seeing their GP.

PMID- 18324506
TI  - Home visits by family physicians in Poland: patients' perspective.

PMID- 18324507
TI  - Angiotensin-converting enzyme inhibitor (ACE-I)- and angiotensin receptor blocker
      (ARB)-related angioedema: a neglected issue in daily practice in Greece.
AB  - Several reports on angioedema (AE) related to the use of angiotensin-converting
      enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) have been
      published recently. This study reports on the experience gained at the Ear, Nose,
      and Throat (ENT) Clinic of the University Hospital of Heraklion, Crete. A
      retrospective chart review of the patients admitted to this clinic, in a 42-month
      period (1999-2003), and discharged with a diagnosis ENT code for AE was performed
      (14 eligible patients). A complementary telephone survey was conducted during
      January 2005. Ten patients responded to our invitation. Of those patients, five
      were under ACE-I and one was under ARB treatment during the AE episode. The mean
      length of time between the onset of symptoms and presentation to the hospital was
      4.5 hours (range 0.5-12 hours). The mean duration between the initiation of
      antihypertensive treatment and AE episode was 26.2 months (range 1-60 months).
      Patients reported that no information was provided about the possible adverse
      effects of these drugs. Although AE introduced by ACE-I and ARBs is an uncommon
      side effect, this case series conveys a key message to primary care physicians.

PMID- 18324508
TI  - Translating and validating an instrument for measuring patients' satisfaction
      with primary care physicians in Palestine: the case of EUROPEP.

PMID- 18324509
TI  - Feasibility of training in problem-solving treatment for general practice
      registrars.

PMID- 18324510
TI  - Specialist training of family physicians in non-UEMO countries: an Estonian
      experience.

PMID- 18324511
TI  - The wind of change: after the European definition--orienting undergraduate
      medical education towards general practice/family medicine.
AB  - Traditionally, medical students are trained in an algorithmic manner, to focus on
      excluding serious but rare diseases by conceptualizing diagnoses through a
      process of exclusion based on systematic and technological investigation of an
      extensive list of potential diagnoses applicable to the patient's presenting
      symptoms and signs. Students are not often exposed to common diseases, and
      trivialize all that which cannot be addressed within a strictly medical model.
      This paper reflects on the recommendations of the EURACT Educational Agenda
      document, and proposes a return to empiricism in basic medical training by
      introducing students to primary healthcare, disease, and decision-making
      processes early in their training. The authors recommend the teaching of
      communication skills within primary care doctor-patient encounters, the
      exploration of new ways of teaching the doctor-patient relationship, and that
      students and young doctors be encouraged to prioritize quality over quantity.
      Will this stem the current trends towards increasing workload and burnout?

PMID- 18324512
TI  - Vasco da Gama Movement: achievements and future plans.

PMID- 18324513
TI  - EGPRN Vilnius meeting 2007: mental health in primary care.

PMID- 18324515
TI  - Trivalent chromium: assessing the genotoxic risk of an essential trace element
      and widely used human and animal nutritional supplement.
AB  - Trivalent chromium [Cr(III)] is recognized as an essential nutrient, and is
      widely used as a nutritional supplement for humans and animals. Recent reports of
      the induction of genetic damage in cultured cells exposed to Cr(III) compounds in
      vitro have heightened the concern that Cr(III) compounds may exert genotoxic
      effects under certain conditions, raising the question of the relative benefit
      versus risk of dietary and feed supplementation practices. We have reviewed the
      literature since 1990 on genotoxic effects of Cr(III) compounds to determine
      whether recent findings provide a sufficient weight of evidence to modify the
      conclusions about the safety of this dietary supplement reached in the several
      comprehensive reviews conducted during the period 1990-2004. The extensive
      literature on genotoxic effects of Cr(III) compounds includes many instances of
      conflicting information, with both negative and positive findings often reported
      in similar test systems. Outcomes of in vitro tests conducted with Cr(III) in
      cultured cells are quite variable regardless of the chemical form of the chromium
      compound tested. The in vitro data show that Cr(III) has the potential to react
      with DNA and to cause DNA damage in cell culture systems, but under normal
      circumstances, restricted access of Cr(III) to cells in vivo limits or prevents
      genotoxicity in biological systems. The available in vivo evidence suggests that
      genotoxic effects are very unlikely to occur in humans or animals exposed to
      nutritional or to moderate recommended supplemental levels of Cr(III). However,
      excessive intake of Cr(III) supplements does not appear to be warranted at this
      time. Thus, like other nutrients that have exhibited genotoxic effects in vitro
      under high exposure conditions, nutritional benefits appear to outweigh the
      theoretical risk of genotoxic effects in vivo at normal or modestly elevated
      physiological intake levels.

PMID- 18324516
TI  - An evaluation of reported no-effect chrysotile asbestos exposures for lung cancer
      and mesothelioma.
AB  - Numerous investigators have suggested that there is likely to be a cumulative
      chrysotile exposure below which there is negligible risk of asbestos-related
      diseases. However, to date, little research has been conducted to identify an
      actual "no-effect" exposure level for chrysotile-related lung cancer and
      mesothelioma. The purpose of this analysis is to summarize and present all of the
      cumulative exposure-response data reported for predominantly chrysotile-exposed
      cohorts in the published literature. Criteria for consideration in this analysis
      included stratification of relative risk or mortality ratio estimates by
      cumulative chrysotile exposure. Over 350 studies were initially evaluated and
      subsequently excluded from the analysis due primarily to lack of cumulative
      exposure information, lack of information on fiber type, and/or evidence of
      significant exposures to amphiboles. Fourteen studies meeting the inclusion
      criteria were found where lung cancer risk was stratified by cumulative
      chrysotile exposure; four such studies were found for mesothelioma. All of the
      studies involved cohorts exposed to high levels of chrysotile in mining or
      manufacturing settings. The preponderance of the cumulative "no-effects" exposure
      levels for lung cancer and mesothelioma fall in a range of approximately 25-1,000
      fibers per cubic centimeter per year (f/cc-yr) and 15-500 f/cc-yr, respectively,
      and a majority of the studies did not report an increased risk at the highest
      estimated exposure. Sources of uncertainty in these values include errors in the
      cumulative exposure estimates, conversion of dust counts to fiber data, and use
      of national age-adjusted mortality rates. Numerous potential biases also exist.
      For example, smoking was rarely controlled for and amphibole exposure did in fact
      occur in a majority of the studies, which would bias many of the reported "no
      effect" exposure levels towards lower values. However, many of the studies likely
      lack sufficient power (e.g., due to small cohort size) to assess whether there
      could have been a significant increase in risk at the reported no-observed
      adverse-effects level (NOAEL); additional statistical analyses are required to
      address this source of bias and the attendant influence on these values. The
      chrysotile NOAELs appear to be consistent with exposure-response information for
      certain cohorts with well-established industrial hygiene and epidemiology data.
      Specifically, the range of chrysotile NOAELs were found to be consistently higher
      than upper-bound cumulative chrysotile exposure estimates that have been
      published for pre-1980s automobile mechanics (e.g., 95th percentile of 2.0 f/ cc
      yr), an occupation that historically worked with chrysotile-containing friction
      products yet has been shown to have no increased risk of asbestos-related
      diseases. While the debate regarding chrysotile as a risk factor for mesothelioma
      will likely continue for some time, future research into nonlinear, threshold
      cancer risk models for chrysotile-related respiratory diseases appears to be
      warranted.

PMID- 18324517
TI  - Physiological endpoints for potential SSRI interactions in fish.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are among the pharmaceutical
      compounds frequently detected in sewage treatment plant effluents and surface
      waters, albeit at very low concentrations, and have therefore become a focus of
      interest as environmental pollutants. These neuroactive drugs are primarily used
      in the treatment of depression but have also found broader use as medication for
      other neurological dysfunctions, consequently resulting in a steady increase of
      prescriptions worldwide. SSRIs, via inhibition of the serotonin (5
      hydroxytryptamine, 5-HT) reuptake mechanism, induce an increase in extracellular
      5-HT concentration within the central nervous system of mammals. The
      phylogenetically ancient and highly conserved neurotransmitter and neurohormone 5
      HT has been found in invertebrates and vertebrates, although its specific
      physiological role and mode of action is unknown for many species. Consequently,
      it is difficult to assess the impact of chronic SSRI exposure in the environment,
      especially in the aquatic ecosystem. In view of this, the current knowledge of
      the functions of 5-HT in fish physiology is reviewed and, via comparison to the
      physiological role and function of 5-HT in mammals, a characterization of the
      potential impact of chronic SSRI exposure on fish is provided. Moreover, the
      insight on the physiological function of 5-HT strongly suggests that the
      experimental approaches currently used are inadequate if not entirely improper
      for routine environmental risk assessment of pharmaceuticals (e.g., SSRIs), as
      relevant endpoints are not assessed or impossible to determine.

PMID- 18324518
TI  - Nitric oxide activated by p38 and NF-kappaB facilitates apoptosis and cell cycle
      arrest under oxidative stress in evodiamine-treated human melanoma A375-S2 cells.
AB  - Nitric oxide (NO) has been identified as a fundamental molecule that interplays
      with reactive oxygen species (ROS) in determining cell fate. As a previous study
      indicated that ROS was stimulated in evodiamine-induced human melanoma A375-S2
      cell apoptosis, the goal of this study was to investigate the role of NO in the
      cells. In this study, it was found that evodiamine has a strong inductive effect
      on NO production synthesized by inducible NOS (iNOS) enzyme in a positive
      feedback manner. The generated NO was further showed to induce apoptosis and cell
      cycle arrest and linked to the activation of p53 and p21. After interruption of
      p38 and nuclear factor-kappaB (NF-kappaB) by pre-treatment with SB203580 and
      PDTC, iNOS expression, NO synthesis and cell damage were all significantly
      blocked. It was concluded that p38 and NF-kappaB were critical to the NO
      producing system, which contributed greatly to the apoptosis and cell cycle
      arrest in evodiamine-incubated cells.

PMID- 18324519
TI  - Involvement of ROS/ASMase/JNK signalling pathway in inhibiting UVA-induced
      apoptosis of HaCaT cells by polypeptide from Chlamys farreri.
AB  - Polypeptide from Chlamys farreri (PCF), a novel marine active material isolated
      from gonochoric Chinese scallop C. farreri, has potential antioxidant activity
      and protective effect against ultraviolet (UV) irradiation. The aim was to
      investigate whether PCF protects HaCaT cells from apoptosis induced by UVA and
      explore related molecular mechanisms. The results showed that PCF significantly
      prevented UVA-induced apoptosis of HaCaT cells. PCF not only strongly reduced the
      intracellular reactive oxygen species (ROS) production, but also diminished
      expression of acid sphingomyelinase (ASMase) and phosphorylated JNK in HaCaT
      cells radiated by UVA in a dose-dependent manner. Pre-treatment with ROS
      scavenger NAC, ASMase inhibitor desipramine or JNK inhibitor SP600125 was found
      to effectively prohibit UVA-induced apoptosis and desipramine markedly blocked
      phosphorylation of JNK. So it is concluded that PCF obviously protects HaCaT
      cells from apoptosis induced by UVA and protective effects may attribute to
      decreasing intracellular ROS level and blocking ASMase/JNK apoptotic signalling
      pathway.

PMID- 18324521
TI  - Effect of N-chloroamino acids on the erythrocyte.
AB  - Amino acids present in blood plasma may be targets for oxidation and chlorination
      by HOCl/OCl(-). N-Chloroamino acids have been reported to be less reactive, but
      more selective than HOCl/OCl(-) in their reactions; therefore, they may act as
      secondary mediators of HOCl/OCl(-)-induced injury. This study compared the
      effects of five N-chloroamino acids (AlaCl, LysCl, SerCl, AspCl and PheCl) on
      erythrocytes with the action of HOCl/OCl(-). The N-chloroamino acids differed in
      stability and reactivity. They had a weaker haemolytic action than HOCl/OCl(-);
      HOCl/OCl(-), AlaCl and PheCl increased osmotic fragility of erythrocytes at a
      concentration of 1 mm. Oxidation of glutathione, formation of protein-glutathione
      mixed disulphides and efflux of GSSG from erythrocytes were observed for
      erythrocytes treated with all the employed chloroderivatives, while increased
      oxidation of 2',7'-dichlorofluorescin was detected only after treatment of the
      cells with 1 mm HOCl/OCl(-), AlaCl and PheCl. Generally, the reactivity of at
      least some N-chloroamino acids may be not much lower with respect to HOCl/OCl(-).

PMID- 18324520
TI  - APE1/Ref-1 regulates PTEN expression mediated by Egr-1.
AB  - APE1/Ref-1, the mammalian ortholog of E. coli Xth, and a multifunctional protein
      possessing both DNA repair and transcriptional regulatory activities, has dual
      role in controlling cellular response to oxidative stress. It is rate-limiting in
      repair of oxidative DNA damage including strand breaks and also has co
      transcriptional activity by modulating genes expression directly regulated by Egr
      1 and p53 transcription factors. PTEN, a phosphoinositide phosphatase, acts as an
      'off' switch in the PI-3 kinase/Akt signalling pathway and regulates cell growth
      and survival. It is shown here that transient alteration in the APE1 level in
      HeLa cells modulates PTEN expression and that acetylatable APE1 is required for
      the activation of the PTEN gene. Acetylation of APE1 enhances its binding to
      distinct trans-acting complexes involved in activation or repression. The
      acetylated protein is deacetylated in vivo by histone deacetylases. It was found
      that exposure of HeLa cells to H(2)O(2) and to histone deacetylase inhibitors
      increases acetylation of APE1 and induction of PTEN. The absence of such
      induction in APE1-downregulated HeLa cells confirmed APE1's role in regulating
      inducible PTEN expression. That APE1-dependent PTEN expression is mediated by Egr
      1 was supported by experiments with cells ectopically expressing Egr-1. Thus, the
      data open new perspectives in the comprehension of the many functions exerted by
      APE1 in controlling cell response to oxidative stress.

PMID- 18324522
TI  - Alterations of erythrocyte structure and cellular susceptibility in patients with
      chronic renal failure: effect of haemodialysis and oxidative stress.
AB  - The aim of this study was to investigate erythrocytes rheological behaviour,
      membrane dynamics and erythrocytes susceptibility to disintegration upon strong
      oxidative stress induced by dialysis or by external H(2)O(2) among patients with
      CRF. EPR spectrometry was used to investigate alterations in physical state of
      cellular components. Generated ROS production induced: (1) significant increase
      of membrane fluidity in CRF erythrocytes treated with H(2)O(2) (p<0.005) and at
      60 min of haemodialysis (p<0.05), (2) significant decrease of cytoskeletal
      protein-protein interactions (p<0.005) and (3) cellular osmotic fragility
      (p<0.0005). H(2)O(2) exacerbated these changes. Erythrocytes from CRF patients
      have changed rheological behaviour and present higher susceptibility to
      disintegration. Erythrocytes membrane characteristics indicate that CRF patients
      possess younger and more flexible cells, which are more susceptible to oxidative
      stress. This may contribute to the shortened survival of young erythrocytes in
      CRF patients.

PMID- 18324523
TI  - Spin labelling of Bacillus anthracis endospores: a model for in vivo tracking by
      EPR imaging.
AB  - Anthrax is caused by the gram-negative bacterium, Bacillus anthracis. Infection
      by this microbe results from delivery of the endospore form of the bacillus
      through direct contact, either topical or inhalation. With regard to the latter
      route of administration, it is proposed that endospores of B. anthracis enter the
      lungs and are phagocytized by host alveolar macrophages. Thereafter, it is
      unclear as to how endospores travel to distal loci and what tissues are the
      targets. Herein, this study describes the spin labelling of endospores through
      two different approaches with various aminoxyls. Indeed, after exposure to RAW
      264.7 cells, these aminoxyl-containing endospores were phagocytized, as
      demonstrated by EPR spectroscopy of the infected macrophage, thus providing a
      potential tool for EPR imaging in animals.

PMID- 18324524
TI  - Protective role of new nitrogen compounds on ROS/RNS-mediated damage to PC12
      cells.
AB  - Reactive oxygen (ROS) and nitrogen (RNS) species are known to be involved in many
      degenerative diseases. This study reports four new nitrogen compounds from
      organic synthesis, identified as FMA4, FMA7, FMA762 and FMA796, which differ
      mainly by the number of hydroxyl groups within their phenolic unit. Their
      potential role as antioxidants was evaluated in PC12 cells by assessing their
      protection against oxidative and nitrosative insults. The four compounds, and
      particularly FMA762 and FMA796, were able to protect cells against lipid
      peroxidation and intracellular ROS/RNS formation to a great extent. Their
      protective effects were likely mediated by their free radicals scavenging
      ability, as they appeared to be involved neither in the induction of natural
      antioxidant enzymes like GSH-PX and SOD, nor in the inhibition of NOS.
      Nevertheless, these results suggest a promising potential for these compounds as
      ROS/RNS scavengers in pathologies where oxidative/nitrosative stress are
      involved.

PMID- 18324525
TI  - Thiols oxidation and covalent binding of BSA by cyclolignanic quinones are
      enhanced by the magnesium cation.
AB  - A novel cyclolignanic quinone, 7-acetyl-3',4'-didemethoxy-3',4'
      dioxopodophyllotoxin (CLQ), inhibits topoisomerase II (TOPO II) activity. The
      extent of this inhibition was greater than that produced by the etoposide quinone
      (EQ) or etoposide. Glutathione (GSH) reduces EQ and CLQ to their corresponding
      semiquinones under anaerobic conditions. The latter were detected by EPR
      spectroscopy in the presence of MgCl(2) but not in its absence. Semiquinone EPR
      spectra change with quinone/GSH mol ratio, suggesting covalent binding of GSH to
      the quinones. Quinone-GSH covalent adducts were isolated and identified by ESI
      MS. These orthoquinones also react with nucleophilic groups from BSA to bind
      covalently under anaerobic conditions. BSA thiol consumption and covalent binding
      by these quinones are enhanced by MgCl(2). Complex formation between the parent
      quinones and Mg(+2) was also observed. Density functional calculations predict
      the observed blue-shifts in the absorption spectra peaks and large decreases in
      the partial negative charge of electrophilic carbons at the quinone ring when the
      quinones are complexed to Mg(+2). These observations suggest a possible role of
      Mg(+2) chelation by these quinones in increasing TOPO II thiol and/or amino/imino
      reactivity with these orthoquinones.

PMID- 18324526
TI  - Insight into the role of CYBA A640G and C242T gene variants and coronary heart
      disease risk. A case-control study.
AB  - The CYBA gene variants have been inconsistently associated with coronary heart
      disease (CHD) risk. A case-control study was conducted genotyping 619 subjects to
      explore the contribution of C242T and A640G to CHD risk in the population. A
      significant risk was found associated with GG homozygosity (odds ratio (OR)
      2.132, 95% confidence interval, 1.113-4.085). The C242T variant was associated
      with CHD risk in women. Bias due to population stratification was analysed.
      Phenotype changes linked to these polymorphisms were evaluated. Superoxide
      measurements revealed higher production as indicated by the presence of the G and
      T alleles. Differences in mRNA concentration in heterozygous A640G samples were
      analysed. Higher levels of G allele mRNA compared with A allele mRNA were found.
      NAD(P)H oxidase p22phox sub-unit expression was evaluated with Western blot.
      Experiments revealed a gradual relationship in p22phox protein expression
      according to genotypes of the analysed variants. Those GG TT double homozygous
      showed increased p22phox protein expressions regarding AA CC double homozygous.
      This study has demonstrated increased expression and activity of the NAD(P)H
      system components during atherogenesis and the results could help explain the
      relevance of the A640G variant as a CHD marker.

PMID- 18324527
TI  - Lycopene-rich treatments modify noneosinophilic airway inflammation in asthma:
      proof of concept.
AB  - Antioxidant-rich diets are associated with reduced asthma prevalence. However,
      direct evidence that altering intake of antioxidant-rich foods affects asthma is
      lacking. The objective was to investigate changes in asthma and airway
      inflammation resulting from a low antioxidant diet and subsequent use of lycopene
      rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10
      days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment
      arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg
      lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid
      concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC
      decreased and %sputum neutrophils increased. Treatment with both tomato juice and
      extract reduced airway neutrophil influx. Treatment with tomato extract also
      reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant
      consumption modifies clinical asthma outcomes. Changing dietary antioxidant
      intake may be contributing to rising asthma prevalence. Lycopene-rich supplements
      should be further investigated as a therapeutic intervention.

PMID- 18324529
TI  - Evaluation of nitrobenzenes and chlorobenzenes levels in samples of sediments
      from Italy: a rapid and simple method by automatic extractor and GC/MS ion trap.
AB  - Ninety-six marine sediment samples from an Italian harbour were analysed by GC/MS
      ion trap for the residues of nitrobenzenes and chlorobenzenes. The significance
      of these compounds in the investigated matrix was discussed. In order to
      determine the simultaneous presence of chlorobenzenes and nitrobenzenes in marine
      sediments, a simple extraction method by an automatic extraction system was
      developed. The use of an automatic extractor unit allows the extraction of the
      analytes of interest with no waste of volatile compounds, since small volumes of
      solvent are required. This also results in a reduction of the analysis time,
      compared with traditional extraction techniques such as extraction by Soxhlet.
      The samples under investigation were mixed with anhydrous sodium sulphate to
      obtain a free-flowing powder and quantitatively transferred into extraction
      thimbles. The thimbles were then introduced into the automatic extractor unit by
      solvent and extracted with 70 mL of acetone/hexane (1:1, v/v). The extract was
      analysed directly by GC/MS ion trap in EI mode. A VF5 ms low bleeding capillary
      column was used to separate the compounds of interest. Recovery rates were
      determined at two spiking levels, one ranging from 1.0 to 5.0 mg/kg, the other
      from 10 to 50 mg/kg. Six replicates were analysed for each fortification level.
      Mean recoveries proved to range from 60.6 to 125.1% in either case. The precision
      of the method was expressed as relative standard deviation (RSD%), which turned
      out to be in the range 5.2-15.0%. The determination limits ranged from 0.01 mg/kg
      to 1.0 mg/kg, when approximately 10 g (dry weight) samples were considered. The
      linearity (r(2) > 0.99) and the limit of detection were also studied.

PMID- 18324530
TI  - Use of model soil colloids to evaluate adsorption of phenanthrene and its
      mobilization by different solutions.
AB  - Inorganic (a montmorillonite; a complex of montmorillonite and aluminium
      hydroxide) and organo-mineral model soil colloids (a complex of montmorillonite,
      aluminium hydroxide and humic acid) were tested for their capacity to adsorb and
      desorb phenanthrene. The adsorption-desorption isotherms demonstrated that the
      inorganic surfaces were able to bind the pollutant, although to a lesser extent
      than the organo-mineral complex. The capacity of different aqueous solutions to
      desorb phenanthrene after 1, 7, and 30 days' contact with the model colloids was
      tested in order to assess their efficacy with respect to the aging effect. The
      solutions used were 0.01 N CaCl(2), dissolved soil organic matter (DOM), a model
      root exudates solution (aqueous solution of saccharose, fructose, glucose,
      fumaric acid, ferrulic acid, and leucine), and three commercial surfactants
      (sodium dodecyl sulfate, Tween 20, and didecyldimethylammonium bromide). The
      desorptive capacity of these solutions were compared with that of organic
      solutions (water-ethanol and n-hexane-ethanol). More than 85% phenanthrene was
      desorbed after 30 days aging by organic solutions. Among the aqueous solutions,
      the best results were obtained with dissolved soil organic matter solution and
      the model root exudates solution which were able to desorb up to 50% phenanthrene
      after 30 days aging. Such naturally occurring aqueous solutions should be
      preferred to synthetic compounds to mobilize phenanthrene in contaminated sites
      without further contaminating the environment.

PMID- 18324531
TI  - Analysis of the toxicity-weighted release amount ranking of PRTR chemicals in
      Japan.
AB  - In this study, toxicity data were first collected for 184 chemicals from reliable
      information sources. After a validity check and analysis of these data, reference
      concentrations (RfC) were determined. The toxicity-weighted release amount (TWR)
      was then calculated for each chemical by dividing the release amounts by the RfC.
      Three types of TWR were derived, namely TWR(atm) for human health protection in
      the atmosphere, TWR(wat) for human health protection in water, and TWR(aq) for
      aquatic life protection. Thus, TWR could be proposed as a new index for
      environmental risk management considering both toxicity and release amount. Based
      on the TWR values, chemicals were ranked according to their potential risk upon
      release. The ranking results revealed that acrolein, formaldehyde, 1,3-butadiene,
      and arsenic are among the substances with the greatest risk to human health
      protection in the atmosphere; acrylonitrile, hydrazine, and pyridine are among
      those detrimental to human health protection in water; and polyoxyethylene alkyl
      ether (POAE), n-alkylbenzene sulfonic acid (LAS), and N,N-dimethyldodecylamine N
      oxide are those identified as posing a risk to aquatic life protection. Moreover,
      for higher TWR chemicals, the contribution of each release source has been
      analyzed and discussed. For example, POAE and LAS are released mainly from
      households, and therefore efforts to reduce their concentration in the
      environment should focus on the sewage system. Formaldehyde and 1,3-butadiene are
      mainly emitted from mobile sources and, therefore, traffic should be evaluated as
      an important release source of toxic chemicals besides many stationary sources.
      Acrylonitrile and arsenic are released mainly by a few specific industries,
      placing the emphasis on the need for responsible care by the individual companies
      involved.

PMID- 18324532
TI  - The effect of particle size and crystal structure of titanium dioxide
      nanoparticles on the photocatalytic properties.
AB  - Titanium dioxide nanoparticles with different average diameter of particles (8,
      18 and 27 nm) and different crystal structure (anatase and rutile) were used for
      degradation of C.I. Acid Red 88 (AR88) as a model compound. The degree of
      degradation of AR88 by TiO(2) nanoparticles under irradiation of UV-light (254nm)
      with TiO(2)-UV100 (8 nm diameter and 100% anatase) is lower than TiO(2)-Merck (27
      nm diameter and 95% anatase). TiO(2)-P25 with structure of anatase and rutile
      (80:20) combination shows higher photoactivity than other samples such as TiO(2)
      UV100 and TiO(2)-Merck. Kinetics of removal of AR88 with all of nanosized-TiO(2)
      particles is pseudo-first-order. The apparent reaction rate constant (k(ap)) for
      removal of AR88 in the presence of different nanosized-TiO2 particles decreases
      with increasing of AR88 initial concentration. For TiO(2)-P25 and TiO(2)-UV100 a
      linear relation and for TiO(2)-Merck a nonlinear relation between k(ap) and light
      intensity were obtained.

PMID- 18324533
TI  - Assessment of water quality conditions in the St. Louis Bay watershed.
AB  - The water quality data from 14 sampling stations in the St. Louis Bay watershed
      were analyzed to evaluate the water quality conditions. The differences in water
      quality parameters between base and storm flow events were compared to identify
      the pollutant sources. The results indicated that fecal coliform was the primary
      cause for water quality impairment of the study area. The overall water quality
      conditions were good in terms of dissolved oxygen, eutrophication, and total
      suspended solid (TSS). The dominant sources of bio-chemical oxygen demand (BOD)
      could be from the failing septic system; the majority of the water samples
      exceeding Mississippi Department of Environmental Quality (MDEQ) target levels
      were from base flow events. Different from BOD, the majority of the water samples
      exceeding the water quality criteria and MDEQ target levels were from the storm
      events for fecal coliform, chemical oxygen demand, total organic carbon, TKN,
      NO(3), NH(3), chlorophyll a, and TSS. Based on cluster analysis, the sampling
      stations were classified into two major categories: upstream and near-coast
      stations. The major differences between upstream and near-coast stations are
      elevation, soil texture, and impacts of human activity. The results from this
      research would provide useful information for total maximum daily load
      calculation, development of a computational watershed model, and development of
      best management practices for the St. Louis Bay watershed and similar study area.

PMID- 18324534
TI  - Oxygen electrode-based single antibody amperometric biosensor for qualitative
      detection of E. coli and bacteria in water.
AB  - Design and performance of an amperometric biosensor for E. coli O157:H7 that is
      based on a common dissolved oxygen probe is discussed. Anti-E. coli O157:H7
      antibody was conjugated to horseradish peroxidase and immobilized on a
      nitrocellulose membrane that was placed over the oxygen probe membrane using a
      custom-fabricated polyvinyl chloride (PVC) insert. Upon bacterial cell binding, a
      decrease in enzyme activity resulted in a change in oxygen concentration that was
      detected with a Clark-type oxygen electrode probe. Validation experiments
      determined the effect of the outer membrane and insert on the Clarke electrode
      performance and linearity, and the effects of stirring on sensor response. The
      mechanism of enzymatic disruption is presumably steric hindrance due to binding
      of the bacterial cell and conformational change in antibody structure. Sampling
      various dilutions of heat-sterilized E. coli O157:H7 cells in water, as little as
      50 bacterial cells/mL could be detected in approximately 20 minutes of sampling
      and processing procedures. Bacterial concentrations from 0 to 5000 cells/mL were
      tested, with 2.52 mg/L +/- 0.37 mg/L equivalents of oxygen produced from as few
      as 50 cells/mL, versus 6.26 +/- 0.64 mg/L when no cells were present in solution.
      Overall, the developed amperometric biosensor technology offered an efficient
      means of detection primarily due to its ease of use, cost-effectiveness,
      portability, and amenability to incorporation at existing water quality gaging
      stations.

PMID- 18324535
TI  - Rapid disinfection of E-Coliform contaminated water using WO3 semiconductor
      catalyst by laser-induced photo-catalytic process.
AB  - Laser-induced photo-catalysis process using WO(3) semiconductor catalyst was
      applied for the study of disinfection effectiveness of E-coliform-contaminated
      water. For this purpose, wastewater polluted with E-coliform bacteria was exposed
      to 355 nm UV radiations generated by third harmonic of Nd: YAG laser in special
      glass cell with and without WO(3) catalyst. E-Coliform quantification was
      performed by direct plating method to obtain the efficiency of each disinfection
      treatment. The dependence of disinfection process on laser irradiation energy,
      amount of catalyst and duration of laser irradiation was also investigated. The
      disinfection with WO(3) was quite efficient inactivating E-coliforms. For
      inactivation of E-coliforms, less than 8 minutes' laser irradiation was required,
      so that, the treated water complies with the microbial standards for drinking
      water. This study opens the possibility of application of this simple method in
      rural areas of developing countries using solar radiation.

PMID- 18324536
TI  - Processing fine stainless-steel slag using spiral concentration.
AB  - In this study, the effectiveness of spiral concentration to process a fine (-1
      mm) stainless-steel slag was evaluated. Specifically, testing was conducted to
      determine the feasibility of producing a high metal content stainless steel
      product and a low metal content aggregate product. This involved investigating a
      key operating variable for both five-and seven-turn spiral concentrators. The raw
      slag and spiral products were characterized to determine their respective size
      and metal distributions. Separation testing was carried out using the two full
      scale spiral concentrators to evaluate the effects of feed solids concentration
      on spiral performance at solids feed rates ranging from 15 to 30 kg/min. The
      results indicated that under certain conditions, a high-quality metal fraction
      could be produced. For example, using the five-turn spiral, a product containing
      95% metal was obtained at a low metal recovery. Both spirals were ineffective at
      concentrating the aggregate fraction. Overall, the feed solids concentration did
      not significantly affect the quality or recoveries of the products, particularly
      for feed solids concentrations less than 35% by weight. In order to improve the
      metal recoveries and to produce a low-metal aggregate material, reprocessing of
      the product streams and/or additional liberation of the raw slag would be
      required.

PMID- 18324537
TI  - Electrochemical-assisted photodegradation of Allura Red and textile effluent
      using a half-exposed rotating TiO(2)/Ti disc electrode.
AB  - In this work, a rotating photoelectrocatalytic (RPEC) reactor, using a half
      exposed and half-immersed TiO(2)/Ti disc as photoanode was developed for the
      first time to degrade Allura Red (AR) and textile effluent. The TiO(2) film was
      characterised by X-ray reflection diffraction (XRD) spectra and field emission
      scanning electron microscope (FESEM). When AR solutions with concentrations
      ranging from 10 mg L(- 1) to 50 mg L(- 1)AR were treated by half-exposed disc PEC
      (EPEC) process for 1 hour, solution color and TOC were reduced by 36-54% and 19
      33%, respectively, higher than reduction of 9-46% and 4-27% observed for the
      conventional PEC (CPEC) process with half TiO(2)/Ti disc immersed in solution.
      Similarly, solution color and TOC for textile effluent was reduced by 46% and 10%
      for EPEC process, respectively, higher than reduction of 26% and 2% for CPEC
      process. Effectiveness of the RPEC process was further demonstrated in the
      treatment of textile effluent and textile effluent containing 30 mgL(- 1) AR by
      determining change of solution color, total organic carbon (TOC), biochemical
      oxygen demand (BOD(5)), and chemical oxygen demand (COD). Furthermore, a long run
      experiment was carried out for the TiO(2)/Ti disc and almost stable photoactivity
      was found after 10 runs of RPEC oxidation of both AR and textile effluent. Our
      results indicate the proposed RPEC is effective in degrading textile wastewater,
      probably because the light can directly irradiate the exposed disc in air instead
      of through solution in the CPEC reactor.

PMID- 18324538
TI  - Phosphorus adsorption characteristics of oyster shells and alum sludge and their
      application for nutrient control in constructed wetland system.
AB  - This research aimed to evaluate the feasibility of employing some locally
      available oyster shells (OS) and alum sludge (AS) as the P adsorption media of
      constructed wetland beds. The batch and column tests were conducted with
      different sizes of OS and AS to observe the P adsorption characteristics and
      breakthrough, while P adsorption rates were determined from jar test. From the
      batch test, the ability to adsorb the amount of added P was different
      considerably between OS and AS media and sizes. At the same size, the P
      adsorption capacities of OS were higher than those of alum sludge. The P
      adsorption capacities of AS with 0.3-0.6 mm and > 0.6 mm sizes were similar, but
      those of 0.3-0.6 mm OS was higher than > 0.6 mm OS. Jar test results revealed the
      first-order P removal rates (k) to be 11.4, 4.5, 1.7 and 1.0 d(- 1) for the 0.3
      0.6 mm AS, > 0.6 mm AS, 0.3-0.6 mm OS, and > 0.6 mm OS, respectively. From the
      column tests, the adsorption capacities were found to be more than 26 and 24.5
      g/kg for the OS media sizes of 0.3-0.6 and > 0.6 mm, respectively, and 12 g/kg
      for the AS media. The column tests revealed that AS was able to adsorb P faster
      than the oyster shells, but due to its low adsorption capacity, the periods of P
      breakthrough in the effluent of the alum sludge columns were shorter than those
      of the oyster shell columns. Experiments with a pilot-scale vertical-flow
      subsurface constructed wetland unit packed with > 0.6 mm OS media demonstrated
      the high P removal efficiencies of more than 96.2% during the 210 days of
      operation.

PMID- 18324539
TI  - Effects of dissolved oxygen on biological nitrogen removal in integrated fixed
      film activated sludge (IFAS) wastewater treatment process.
AB  - The objective of this research was to determine the effects of dissolved oxygen
      on the biological nitrogen removal in the Integrated Fixed Film Activated Sludge
      (IFAS) and Modified Ludzack-Ettinger (MLE) systems. The carbonaceous and nitrogen
      removals were investigated at the COD/Nitrogen (C/N) ratios of 4, 6, and 10, and
      the dissolved oxygen (DO) concentrations of 2, 4, and 6 mg/L. The experimental
      results indicate that the C/N ratios of 4, 6, and 10 and the DO concentrations of
      2, 4, and 6 affected insignificantly on the chemical oxygen demand (COD) removal,
      but significantly on the nitrogen removal as the consequences of different
      nitrification and denitrifcation rates in both systems. The COD removal was
      nearly completed throughout this study because glucose was used as a primary
      carbon source in the wastewater and both systems were operated at high SRT
      relative to the minimum SRT requirement for COD removal. The experimental
      conditions used in this study apparently led to nitrite accumulation in both IFAS
      and MLE systems. It is suggested that there is no benefit of installing media in
      the IFAS system at the C/N ratio of 10 because the system was underloaded with
      the nitrogen. The lower DO concentration, the greater denitrification in the
      anoxic zone was achieved because nitrite nitrogen was used as an electron
      acceptor. At the C/N ratios of 4 and 6, the IFAS system was higher in capacity
      for nitrification as a result of attached biomass on the support media in the
      aerobic zone. The DO concentration of 6 mg/L is required to maximize the
      nitrification rates in the systems under these experimental conditions resulting
      in greater oxidized nitrogen for denitrification in the anoxic zones. The
      denitrification in the aerobic zone of the IFAS system is not evaluated due to
      unavailability of nitrite information. The optimal DO concentrations for
      biological nitrogen removal in the IFAS system at the C/N ratios of 4, 6, and 10
      in this study were 6, 6, and 2 mg/L, respectively.

PMID- 18324540
TI  - Preliminary evaluation of galvanic sludge immobilization in clay-based matrix as
      an environmentally safe process.
AB  - This study attempts to determine the possibilities and limitations of the
      immobilization of galvanic wastes by their incorporation into clay-based
      materials. It focuses on the effects of several processing parameters such as the
      temperature of thermal treatment, the relative amount of sludge, and the physico
      chemical aspects of the sample, on the fixing level of relevant metals (Zn, Ni,
      Fe, Mn, Pb, Cu, Cr) in thermally treated clay-based samples. The effectiveness of
      sludge inactivation was assessed by water-leaching test and conductivity
      measurements. In view of the potential use of the sludge stabilization products
      as construction materials, the linear shrinkage and bending strain of the fired
      samples was investigated. To characterize their morphology, mineralogy and
      composition, fired samples of clay and its mixtures with galvanic sludge were
      studied on a scanning electron microscope (SEM) coupled with an energy dispersive
      X-ray analyser (EDS) and X-ray diffractometer (XRD). It was found that the
      efficiency of metal immobilization is dependent on the clay composition and the
      temperature of the thermal treatment of the prepared mixtures. The thermal
      treatment of all samples at all temperatures resulted in the stabilization of all
      heavy metal ions (copper, nickel, iron, lead, manganese and zinc) with the
      exception of chromium.

PMID- 18324541
TI  - Long-term assessment of nitrification in a full-scale wastewater treatment plant.
AB  - In this study, long term nitrification performances and microbial composition in
      a full-scale oxidation ditch type wastewater treatment plant (WWTP) were
      monitored and evaluated using different molecular methods; fluorescent in situ
      hybridization (FISH), slot-blot hybridization and quantitative real-time
      polymerase chain reaction (PCR) method. In situ and membrane hybridization
      results indicated that Nitrosomonas species were identified as the dominant
      ammonia oxidizing bacteria and Nitrospira related species were detected as the
      prevailing nitrite oxidizing bacteria in a full-scale wastewater treatment plant
      throughout 2 years of operation. Real-time PCR using the LightCyclerinstrument
      has been developed for the quantification of ammonia monooxygenase (amoA) and 16S
      rRNA genes. Results suggest that real-time PCR analysis, amoA/16S rRNA ratio, is
      an alternative method to understand nitrifying bacterial population and activity
      in wastewater treatment plant compared with the FISH and slot-blot hybridization
      assays. The autotrophic/heterotrophic bacterial ratio and their influence on
      reactor performances were investigated using real-time PCR amoA/16S rRNA gene
      copy ratios and the results showed that this ratio varied from 3.6% to 8.3%
      during operational period.

PMID- 18324542
TI  - Body size and population growth of Brachionus patulus (Rotifera) in relation to
      heavy metal (copper and mercury) concentrations.
AB  - The effect of different sublethal concentrations of Cu(+ 2) and Hg(+ 2) was
      evaluated on the population growth and morphometry (body width and postero
      lateral spines) of Brachionus patulus. When exposed to Cu(+ 2) at lower
      concentrations (i.e., 2.5% and 5.0% of LC(50)), the population growth of B.
      patulus did not differ significantly from controls, while at the corresponding
      conditions, Hg(+ 2) had adverse effects. The rate of population increase (r)
      varied from 0.13 to 0.28 per day, depending on the metal type and its
      concentration in the medium. In general, increase in metal concentration
      decreased the rate of population increase. When the daily growth rate was plotted
      as function of population density over the entire growth phase, a significantly
      inverse relation was obtained for controls and in treatments containing lower
      concentrations (2.5 and 5% of LC(50)) of heavy metals. However, under higher
      metal concentrations, the relation between population density and the daily
      growth rate became non-significant. Morphometric data showed that Cu caused
      larger bodied individuals, while the opposite effect was resulted due to Hg(+ 2).
      Postero-lateral spines of B. patulus were also significantly influenced by the
      concentration of Cu(+ 2) or Hg(+ 2). Thus, compared to controls, there was
      reduction in the spine length, at low concentrations of Cu(+ 2), but at all the
      four tested levels of Hg(+ 2). Our data suggested that in addition to the
      population growth rate, morphometric measurements need to be considered for
      understanding the impact of heavy metals to brachionid rotifers.

PMID- 18324543
TI  - Electrocoagulation study for the removal of arsenic and chromium from aqueous
      solution.
AB  - This study was undertaken to investigate the removal of arsenic (As) and chromium
      (Cr) from aqueous solution using electrocoagulation (EC) technique. Batch EC
      studies were performed using iron electrodes to evaluate the influence of various
      experimental parameters on the removal of metal ions. The parameters were initial
      pH (pH(0)), electrolysis time (t), initial concentration (C(0)), electrode gap
      (g), stirring rate (r) and current density (j). Effect of pH(0) was studied in
      the range 2.0 to 8.0 while C(0) was varied from 10 to 100 mg/L. As and Cr removal
      by EC was governed by the chemical dissolution of iron, and the formation of
      metal-hydrous ferric oxide complexes, which in turn was strongly, influenced by
      pH(0) and j. Optimum value of pH(0) and j for As and Cr removal were found to be
      4.0 and 2.0; and 75 and 50 A/m(2), respectively. Removal efficiency increased
      with decrease in the value of C(0) and g. The r value of 100 rpm produced
      sufficient agitation for the proper agglomeration of flocs and optimum removal of
      ions.

PMID- 18324544
TI  - Cadmium, zinc, copper, sodium and potassium concentrations in rooster and turkey
      semen and their correlation.
AB  - The purpose of this study was to assess concentration of selected elements
      (cadmium, zinc, copper, sodium and potassium) in rooster and turkey semen and to
      find possible correlations between these elements. Samples were analyzed on the
      atomic absorption spectrophotometer. The analysis of cadmium showed that the
      concentration in rooster is 9.06 +/- 7.70 and in turkey 4.10 +/- 3.59 microg/mL.
      In zinc 5.25 +/- 1.96 microg/mL in rooster and 3.70 +/- 1.26 microg/mL in turkey
      were detected. Higher concentration of copper was found in rooster semen (6.79 +/
      6.42 microg/mL) in comparison with turkey semen (4.29 +/- 5.43 microg/mL). The
      level of sodium (3.96 +/- 1.02 microg/mL; 3.14 +/- 0.85 microg/mL) and potassium
      (2.88 +/- 0.65 microg/mL; 3.42 +/- 1.41 microg/mL) was very similar in both
      species. Correlation analysis detected high positive correlation between cadmium
      and zinc (r = 0.701) in rooster and between sodium and potassium (r = 0.899) in
      turkey semen.

PMID- 18324545
TI  - From individual to collective memory: theoretical and empirical perspectives.

PMID- 18324546
TI  - Towards a psychology of collective memory.
AB  - This article discusses the place of psychology within the now voluminous social
      scientific literature on collective memory. Many social scientists locate
      collective memories in the social resources that shape them. For scholars
      adopting this perspective, collective memories are viewed as transcending
      individuals; that is, as being "in the world". Others recognise that, in the
      final analysis, individuals must remember collective as well as individual
      memories. These scholars treat collective memories as shared individual memories.
      We attempt to bridge these two approaches by distinguishing between the design of
      social resources and memory practices, on one hand, and on the other, the
      effectiveness of each in forming and transforming the memories held by
      individuals and the psychological mechanisms that guide this effectiveness.

PMID- 18324547
TI  - The development of collective remembering.
AB  - This essay outlines a sociocultural, developmental approach to collective memory.
      This work is grounded in Halbwachs' (1950/1980) theory of collective memory and
      in recent prospective studies of collective remembering within families from
      early childhood through adolescence. The claim is that the basic process of
      collective remembering is present from the earliest conversations about the past
      between parents and children, but it is not until adolescence that collective
      memory is informed by family stories and by history. There are both positive and
      negative consequences of collective remembering as a function of the nature of
      the collective. In conclusion, researchers are urged to broaden their view of the
      collective in their studies of autobiographical and collective memory.

PMID- 18324548
TI  - Collaborative recall and collective memory: what happens when we remember
      together?
AB  - Studies of collective memory have traditionally been the domain of philosophers
      and sociologists, while cognitive psychologists have largely investigated memory
      at the level of the individual. However, within cognitive psychology there is a
      variety of psychological theories and experimental paradigms that have been used
      to study the process and outcomes of remembering in groups. In this paper we
      review the research on group remembering and draw together findings from
      different traditions. In doing so, we aim to answer a series of questions about
      the outcomes and consequences of recalling in groups, and the particular features
      of groups and of memories that may be conducive to the formation of a collective
      memory. In clarifying what we know and what is yet to be studied about group
      memory, we point the way forward for a cognitive psychological study of
      collective memory.

PMID- 18324549
TI  - Influence of re-exposure and retrieval disruption during group collaboration on
      later individual recall.
AB  - This research examined the influence of prior group collaboration on later
      individual recall. We considered the negative effects of retrieval disruption and
      the potentially positive effects of re-exposure to additional items during group
      recall in the context of three hypotheses: the individual-strategy hypothesis,
      the combined-strategy hypothesis, and the group-strategy hypothesis. After a
      study phase and a brief delay, participants completed three successive recall
      trials in four different recall sequence conditions: III (individual-individual
      individual), ICI (individual-collaborative-individual), CII (collaborative
      individual-individual), and CCI (collaborative-collaborative-individual). Results
      show that repeated group recalls (CCI), and securing individual retrieval
      organisation prior to group recall (ICI), benefit later individual recall more
      than repeated individual recalls (III). These findings support the group-strategy
      hypothesis and the individual-strategy hypothesis, and have important
      implications for group versus individual learning practices in educational
      settings.

PMID- 18324550
TI  - Collaborative recall in face-to-face and electronic groups.
AB  - When people remember shared experiences, the amount they recall as a
      collaborating group is less than the amount obtained by pooling their individual
      memories. We tested the hypothesis that reduced group productivity can be
      attributed, at least in part, to content filtering, where information is omitted
      from group products either because individuals fail to retrieve it or choose to
      withhold it (self-filtering), or because groups reject or fail to incorporate it
      (group-filtering). Three-person groups viewed a movie clip together and recalled
      it, first individually, then in face-to-face or electronic groups, and finally
      individually again. Although both kinds of groups recalled equal amounts, group
      filtering occurred more often face-to-face, while self-filtering occurred more
      often electronically. This suggests that reduced group productivity is due not
      only to intrapersonal factors stemming from cognitive interference, but also to
      interpersonal costs of coordinating the group product. Finally, face-to-face
      group interaction facilitated subsequent individual recall.

PMID- 18324551
TI  - You say tomato? Collaborative remembering leads to more false memories for
      intimate couples than for strangers.
AB  - Research on memory conformity shows that collaborative remembering--typically in
      the form of discussion--can influence people's memories. One question that
      remains is whether it matters with whom we discuss our memories. To address this
      question we compared people's memories for an event after they discussed that
      event with either their romantic partner or a stranger. Pairs of subjects watched
      slightly different versions of a movie, and then discussed some details from the
      movie, but not others. Subjects were better at remembering non-discussed details
      than discussed details: when remembering discussed details they incorrectly
      reported information from their partner's version instead of their own. In
      addition, subjects who discussed the event with their romantic partner (rather
      than with a stranger) were even more likely to report false memories. We discuss
      our findings in relation to other research on memory conformity, social
      influences on false memories, and memory systems within romantic relationships.

PMID- 18324552
TI  - Performance and process in collective and individual memory: the role of social
      decision schemes and memory bias in collective memory.
AB  - To assess performance and processes in collective and individual memory,
      participants watched two job candidates on video. Beforehand, half the
      participants were told they would be tested on their memory of the interviews,
      and the other half were asked to make a decision to hire one of the candidates.
      Afterwards, participants completed a recognition memory task in either a group or
      individual condition. Groups had better recognition memory than individuals.
      Individuals made more false positives than false negatives and groups exaggerated
      this. Post-hoc analysis found that groups only exaggerated the tendency towards
      false positives on items that reflected negatively on the job candidate. There
      was no significant difference between instruction conditions. When reaching
      consensus on the recognition task, groups tended to choose the correct answer if
      at least two members had the correct answer. This method of consensus is
      discussed as a factor in groups' superior memory performance.

PMID- 18324553
TI  - Collective memory: a perspective from (experimental) clinical psychology.
AB  - This paper considers the concept of collective memory from an experimental
      clinical psychology perspective. Exploration of the term collective reveals a
      broad distinction between literatures that view collective memories as a property
      of groups (collectivistic memory) and those that regard these memories as a
      property of individuals who are, to a greater or lesser extent, an integral part
      of their social environment (social memory). First, we argue that the
      understanding of collectivistic memory phenomena may benefit from drawing
      parallels with current psychological models such as the self-memory system theory
      of individualistic autobiographical memory. Second, we suggest that the social
      memory literature may inform the study of trauma-related disorders. We argue that
      a factual focus induced by collaborative remembering may be beneficial to natural
      recovery in the immediate aftermath of trauma, and propose that shared
      remembering techniques may provide a useful addition to the treatment of post
      traumatic stress disorder.

PMID- 18324554
TI  - On the cultural constitution of collective memory.
AB  - The study of collective memory needs to take into consideration the cultural
      context in which the remembering takes place. In this article, I analyse how
      functional variations of collective memory across cultures may influence the
      processes, practices, and outcomes of collective remembering. I then discuss the
      transitory nature of culture in affecting collective memory across an
      individual's lifespan as well as across time and generations. I borrow recent
      findings from cross-cultural research on autobiographical memory to illustrate
      the cultural effects, and propose a new approach to studying collective memory in
      which the individual, the collective, and the culture are treated as a single
      unit of analysis.

PMID- 18324555
TI  - Collective memory: conceptual foundations and theoretical approaches.
AB  - In order to outline the conceptual landscape that frames discussions of
      collective memory, three oppositions are proposed: collective memory versus
      collective remembering; history versus collective memory; and individual memory
      versus collective remembering. From this perspective collective remembering is
      viewed as an active process that often involves contention and contestation among
      people rather than a static body of knowledge that they possess. Collective
      remembering is also viewed as privileging identity formation and contestation
      over the sort of objective representation of the past that is the aspiration of
      formal historical analysis. And finally, while collective remembering involves
      individual minds, it also suggests something more in the form of socially
      situated individuals, a claim that can usefully be formulated in terms of how
      members of a groups share a common set of cultural tools (e.g., narrative forms)
      and similar content.

PMID- 18324556
TI  - What's new in nicotine & tobacco research?

PMID- 18324557
TI  - The effectiveness of smoking cessation interventions prior to surgery: a
      systematic review.
AB  - The objective of this review was to evaluate the effectiveness of smoking
      cessation interventions prior to surgery and examine smoking cessation rates at 6
      months follow-up. The Cochrane Library Database, PsycINFO, EMBASE, Medline, and
      Cinahl databases were searched using the terms: smok$, smoking cessation,
      tobacco, cigar$, preop$, operati$, surg$, randomi*ed control$ trial,
      intervention, program$, cessation, abstinen$, quit. Further articles were
      obtained from reference lists. The search was limited to articles on adults,
      written in English and published up to December 2006. Only randomized control
      trials (RCTs) that incorporated smoking cessation interventions to patients
      awaiting elective surgery were included. Seven studies met the inclusion
      criteria. Methodological quality was assessed by all the authors. The findings
      revealed that short-term quit rates (or a reduction by more than half of normal
      daily rate) ranged from 18% to 93% in patients receiving a smoking intervention
      (mean 55%), compared with a range of 2%-65% of controls (mean = 27.7%). Two
      studies examined smoking status at 6 months but these revealed no significant
      difference in abstinence rates between patients who had received an intervention
      and those that had not. Studies that incorporated counseling in addition to
      nicotine replacement therapy appeared to show greater benefits. It is concluded
      that smoking cessation interventions prior to surgery are effective in helping
      patients to quit smoking. However, such effects appear to be short-lived. Future
      research needs to examine intervention and patient factors to see whether
      tailoring the smoking cessation intervention specifically to the patient improves
      overall abstinence rates.

PMID- 18324558
TI  - Health perceptions of home-grown tobacco (chop-chop) smokers.
AB  - We present results from a qualitative study of smokers of home-grown tobacco
      (chop-chop). In particular, we focused on participants' perceptions of the health
      effects of smoking chop-chop relative to legal tobacco. Consistent with previous
      work, we found that smokers of chop-chop believe that relatively less chemical
      treatment of chop-chop tobacco meant lower health risks than with legal products,
      although many believed the ultimate difference in effect on health was
      negligible.

PMID- 18324559
TI  - Nicotine delivery, cardiovascular profile, and subjective effects of an oral
      tobacco product for smokers.
AB  - The tobacco industry markets potential reduced exposure products (PREPs) to
      smokers, including oral products that are intended to be used in situations where
      cigarettes cannot. For example, Ariva, marketed by Star Scientific, is a tablet
      made from compressed tobacco powder and is intended for "adult smokers in
      situations where they cannot or choose not to smoke." No objective data are
      available regarding Ariva's effects in smokers, including its nicotine delivery,
      cardiovascular profile, or subjective effects. In this single-session, clinical
      laboratory study, 10 overnight-abstinent cigarette smokers were administered one
      Ariva tablet, followed 90 min later by two Ariva tablets, followed 90 min later
      by three Ariva tablets. Participants allowed each dose to dissolve in their
      mouths according to package instructions. Blood was sampled, heart rate
      monitored, and subjective effects assessed regularly. Ariva delivered nicotine in
      a dose-dependent manner; mean (SD) nicotine levels increased from 2.4 ng/ml (0.9)
      at baseline, to 3.4 ng/ml (1.4) 45 min post-1 tablet, 7.3 ng/ml (4.0) 45 min post
      2 tablets, and 9.7 ng/ml (4.4) 45 min post-3 tablets. Heart rate increased after
      tablet administration, independent of dose. The tablets also significantly
      decreased subjective ratings of craving and urge, and increased ratings of
      nausea. Based on this short-term laboratory evaluation, Ariva exposes users to
      nicotine and may suppress some symptoms of tobacco abstinence, though its nausea
      inducing characteristics may limit initial acceptability.

PMID- 18324560
TI  - Smoking reduction predicts cessation: longitudinal evidence from the Finnish
      adult twin cohort.
AB  - The aim of the study was to examine whether smoking reduction over a 6-year
      period (1975-1981) predicted smoking cessation 9 years later by 1990. The
      longitudinal data from three surveys over 15-year period among the Finnish adult
      twin cohort were used. The data were collected by postal surveys in 1975, 1981,
      and 1990, and the sample comprised 11,015 participants, of whom 2,443 were
      persistent current smokers in 1975 and 1981. Smoking cessation by 1990 was
      examined as the outcome measure. Nineteen percent reported having stopped smoking
      by 1990, corresponding to an approximate annual rate of smoking cessation of 2%.
      Those who had quit smoking by 1990 had larger decreases in smoking between 1975
      and 1981. The odds ratio for quitting by 1990 increased with increasing levels of
      reduction in amount smoked between 1975 and 1981. This was found in both
      categorical and trend analyses, and when adjusting for age, sex and for amount of
      baseline smoking. The model among twin pairs discordant for cessation indicated
      that the association of smoking reduction with increased likelihood of cessation
      was independent of genetic or early shared family influences on smoking behavior.
      We conclude that smokers who are able to decrease the number of cigarettes smoked
      per day by at least 25% are more likely to quit later.

PMID- 18324561
TI  - Contribution of occupational factors to current smoking among active-duty U.S.
      Navy careerists.
AB  - Rates of cigarette smoking among active-duty U.S. military personnel remain
      elevated, ranging from 23% among Air Force personnel to 38% among Army personnel.
      The purpose of this study was to estimate the contribution of occupational
      factors to current smoking and heavy smoking among a sample of Navy careerists
      (those with at least 7 years of military service), and to determine if gender
      moderates these associations. Participants in the study (n = 2,922) were randomly
      recruited within over-sampled strata of women and racial/ethnic minorities, and
      voluntarily completed confidential self-administered questionnaires on drinking,
      smoking, demographic, and occupational factors during 2001-2002. Approximately
      23% of study participants reported current smoking; 9% reported heavy smoking.
      Multivariate logistic regression models were developed to estimate the
      contribution of occupational factors to current smoking and heavy smoking. The
      results indicated that careerists in the enlisted ranks were significantly more
      likely to be current smokers and heavy smokers compared with careerist officers.
      In addition, those who were deployed at sea were significantly more likely to
      report current smoking compared with those not currently deployed at sea. Mean
      daily ounces of alcohol were also significantly associated with likelihood of
      current and heavy smoking. Gender did not modify the association between
      occupational factors and smoking. Because aspects of the work environment are
      potentially modifiable, understanding the role of occupational factors vis-a-vis
      smoking can aid in smoking prevention and cessation efforts within the military.

PMID- 18324562
TI  - The role of psychiatric disorders in the relationship between cigarette smoking
      and DSM-IV nicotine dependence among young adults.
AB  - This study set out to evaluate the association between cigarette smoking and
      nicotine dependence (Diagnostic and Statistical Manual of Mental Disorders [4th
      ed.]) (DSM-IV), and to determine whether psychiatric disorders may signal greater
      sensitivity to nicotine dependence at similar levels of smoking exposure. Drawing
      on the young adult sample (aged 18-25 years) from the National Epidemiologic
      Survey of Alcohol and Related Conditions (NESARC), we conducted logistic
      regression analyses. Smokers with major depression, alcohol use disorders, or
      specific phobia had a higher risk of meeting DSM-IV criteria for nicotine
      dependence than did those without these disorders. When examining smoking
      quantity, we found that rates of nicotine dependence were similar for those with
      and without major depression among nondaily smokers, yet among daily smokers,
      rates of nicotine dependence were consistently higher among those with major
      depression than among those without. Alcohol dependence elevated the risk of
      nicotine dependence at low to moderate levels of use. However, no difference in
      risk for nicotine dependence was observed between alcohol-dependent and
      nondependent individuals smoking more than a pack a day. Increased risk of
      nicotine dependence among those with a specific phobia was consistent across the
      range of current smoking levels. These findings add to the growing literature
      documenting dependence in nondaily smokers and demonstrate that although chronic
      smoking is often a key feature in dependence, psychiatric disorders may signal
      greater sensitivity to nicotine dependence symptoms at substantially lower levels
      of smoking exposure.

PMID- 18324563
TI  - The relationship between cigarette use, nicotine dependence, and craving in
      laboratory volunteers.
AB  - Data from epidemiological studies suggest that individual differences in
      cigarettes per day (CPD) and duration of smoking account for only a small portion
      of the variance in Diagnostic and Statistical Manual of Mental Disorders (4th
      ed.) (DSM-IV) nicotine dependence. However, DSM-IV may be an insensitive measure
      of nicotine dependence; other measures might better reflect the true nature of
      the relationship between use and dependence. This paper describes the
      relationship between cigarettes per day (CPD) and years smoking and the severity
      of nicotine dependence as measured by the Nicotine Dependence Syndrome Scale
      (NDSS). Furthermore, we assessed the validity of individual differences in
      nicotine dependence by determining whether they related to cue-evoked craving
      during abstinence. Data were pooled from five laboratory studies of 489 regular
      (i.e., 15+ CPD) smokers. In contrast to previously reported data demonstrating a
      relatively strong relationship between CPD and dependence in chippers (Shiffman &
      Sayette, 2005), CPD and years smoking accounted for a statistically significant,
      but small (<6%), portion of the variance in nicotine dependence in daily smokers.
      Individual differences in both CPD and years smoking had little or no
      relationship with craving. However, the magnitude of craving was significantly
      related to the degree of nicotine dependence even after controlling for use
      variables and excluding craving-related items on the NDSS. These data suggest
      that among moderate to heavy daily smokers, meaningful individual differences in
      nicotine dependence are observed independent of differences in current daily
      cigarette consumption and duration of smoking. Further research into the sources
      of this variance is critical to understanding the process of and risk for
      nicotine dependence.

PMID- 18324564
TI  - Menthol cigarettes and smoking cessation during an aided quit attempt.
AB  - Menthol may make cigarettes more addictive and rates of menthol cigarette smoking
      are disproportionately higher among Black. However, few studies have examined the
      association between menthol cigarette smoking and cessation, and the studies to
      date have produced conflicting findings. The present study examines the effect of
      menthol cigarette smoking on cessation among a multi-ethnic sample of smokers
      making a pharmacotherapy-aided quit attempt. We hypothesized that menthol
      cigarette smoking would be associated with lower smoking abstinence rates and
      conducted a secondary analysis of data from a multi-site randomized controlled
      trial of an intervention designed to facilitate repeat tobacco cessation
      treatment (N = 1,343). The intervention consisted of a patient phone call and a
      computerized provider prompt. The primary outcome for this analysis was 7-day
      point prevalence smoking abstinence. The average age of the sample was 56 years
      old. Overall, 25% of the sample smoked menthol cigarettes: 19% of Whites, 62% of
      Blacks, and 25% of other ethnicity (p<.001). We observed no significant effects
      for menthol cigarette smoking or ethnicity on smoking abstinence rates. In
      conclusion, combined with findings from previous research, this study suggests
      that smoking menthol cigarettes does not decrease smoking cessation among older
      smokers during a quit attempt aided with pharmacotherapy.

PMID- 18324565
TI  - Older versus younger treatment-seeking smokers: differences in smoking behavior,
      drug and alcohol use, and psychosocial and physical functioning.
AB  - Quitting smoking benefits older individuals, yet few recent studies have
      described older smokers. The goal of this paper was to test a series of
      hypotheses about differences between smokers aged 50 years or older (50+) and
      those younger than age 50 (<50) presenting to the same treatment facility during
      2002-2004 for participation in two randomized clinical trials: one exclusively
      for smokers aged 50+, and a second open to smokers aged 18 or older. As
      predicted, smokers aged 50+ were more tobacco dependent, had better psychological
      functioning, and had poorer physical functioning than those aged <50. Contrary to
      predictions, we found no differences in motivation to quit cigarette smoking or
      in alcohol use. Women aged 50+ were less likely to report marijuana use than
      women aged <50, and less likely than men to receive a positive diagnosis for
      alcohol abuse. Despite higher scores on measures of tobacco dependence, older
      smokers were less likely to be diagnosed as tobacco dependent or as having
      tobacco withdrawal using DSM-IV criteria. Rates of DSM-IV alcohol abuse and
      dependence were high in both age groups but were higher for smokers aged <50. We
      found no striking differences between studies in reasons for exclusion, but in
      both the proportion of individuals excluded due to current antidepressant use was
      high. Implications for the assessment and treatment of older adults are
      discussed.

PMID- 18324566
TI  - Smoking reduction fails to improve clinical and biological markers of cardiac
      disease: a randomized controlled trial.
AB  - Cigarette reduction has been proposed as a treatment goal for smokers who are not
      interested in stopping completely. This randomized controlled trial was designed
      to determine the effect of a smoking reduction intervention on smoking behavior,
      symptoms of heart disease, and biomarkers of tobacco exposure. It included 152
      patients with heart disease who did not intend to stop smoking in the next 30
      days. Participants were randomly assigned to smoking reduction (SR) or usual care
      (UC). SR subjects received counseling and nicotine replacement therapy to
      encourage > or =50% reduction in cigarettes per day (CPD). They were followed at
      1, 3, 6, 12 and 18 months to assess smoking, heart disease symptoms, quality of
      life and nicotine, cotinine, carbon monoxide (CO), white blood cell (WBC) count,
      fibrinogen, hs-C-reactive protein (hs-CRP), F2-isoprostane, 4-(methylnitrosamino)
      1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and 1-hydroxypyrene (1
      HOP). At 6 months SR participants reduced by 10.9 CPD, compared with 7.4 CPD in
      UC (difference NS). At 18 months, 9/78 SR vs. 9/74 UC participants quit smoking.
      There were no significant differences between treatment groups in angina, quality
      of life or adverse events, nicotine, cotinine, CO, WBC count, fibrinogen, hs-CRP,
      F2-isoprostane, total NNAL or 1-HOP levels at any time point. To determine if
      smoking reduction, regardless of treatment condition, was associated with
      improved outcomes, we compared all subjects at 6 months to baseline (mean
      reduction in CPD from 27.4 to 18.1, p<.01). There were no significant changes in
      outcome variables except CO, which decreased by 5.5 ppm (p<.01). There were also
      no significant improvements considering only subjects who reduced by > or =50%,
      or those who had no history of reduction prior to enrollment in the study. The SR
      intervention did not significantly reduce CPD or toxin exposure, or improve
      smoking cessation or clinical outcomes compared to UC. These results emphasize
      the importance of abstinence for smokers with heart disease to minimize health
      risks from tobacco.

PMID- 18324567
TI  - Prevalence of smoking and its relationship with carotid atherosclerosis in
      Alaskan Eskimos of the Norton Sound region: the GOCADAN study.
AB  - Since 2000, the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN)
      study has been collecting information on cardiovascular disease (CVD) and its
      risk factors from 1,214 Alaska Natives of the Norton Sound region, a population
      with increasing rates of heart disease and stroke. Because smoking was reported
      in a large proportion of the participants, this analysis was undertaken to
      evaluate smoking patterns and their relation to other risk factors and to CVD.
      The relationships among smoking habits and demographic factors, body mass index,
      plasma fibrinogen, prevalent hypertension, and carotid plaque were evaluated.
      Eighty percent of participants had smoked 100+ cigarettes in their lifetime.
      Fifty-seven percent of women and 63% of men (p = .12) were current smokers: one
      in four smokers had quit. Current smokers (OR = 2.1; 95% CI = 1.1-3.8) and those
      who had quit <5 years ago (OR = 1.6; 95% CI = 1.1-2.2) were more likely than non
      smokers to have carotid plaque. Pack-years smoked also were correlated with
      carotid plaque. The high prevalence of smoking and low rates of cessation in this
      population demonstrate an urgent need for smoking prevention and cessation
      programs among Alaskan Eskimos of the Norton Sound region and other Alaska Native
      groups.

PMID- 18324568
TI  - A qualitative study on establishing and enforcing smoking rules in family cars.
AB  - With continued expansion of clean indoor air legislation, private spaces such as
      homes and cars are gaining increased attention as significant sources of
      secondhand smoke (SHS). This study examines the establishment and enforcement of
      smoking rules in family cars. Qualitative interviews (N = 136) were conducted
      with Black and White families in rural Georgia. Participating families had a
      young adolescent in the home and included households with all nonsmokers, a mix
      of smokers and nonsmokers, and all smokers. Common car smoking rules included no
      smoking allowed at any time, smoking allowed if a window is cracked, and no
      smoking allowed if children or nonsmokers are in the car. Major reasons for rules
      included protecting children and nonsmokers from SHS, aversion to the smell, and
      the stifling nature of SHS in cars. Damage to the vehicle from ashes and burns
      was another reason for smoking rules, particularly among families with smokers.
      Many families had never discussed car smoking rules. Families with car smoking
      rules were generally able to enforce them without difficulty, although smokers
      responded with a range of reactions from acceptance to anger. Families would
      consider a total ban if the smoker in their family quit or, for a few, if they
      purchased a new car. These findings have implications for designing intervention
      strategies to promote smoke-free cars and help family members to negotiate and
      enforce car smoking rules.

PMID- 18324569
TI  - Susceptibility to smoking and its association with physical activity, BMI, and
      weight concerns among youth.
AB  - Research has yet to examine how physical activity, body mass index (BMI) and
      concerns about weight among youth populations are associated with susceptibility
      to smoking among never smokers. The Physical Activity Module of the School Health
      Action, Planning and Evaluation System (SHAPES) was completed by 25,060 students
      in grades 9 to 12 within 76 secondary schools in Ontario (Canada) to examine how
      being overweight, weight concerns, and physical activity are associated with
      susceptibility to smoking in a large sample of youth. Among the 14,795 students
      who were never smokers, 3,809 (25.8%) were classified as susceptible to future
      smoking and 10,986 (74.2%) were classified as non-susceptible to future smoking.
      Smoking susceptibility was negatively associated with being highly active or at
      risk of overweight and positively associated with perceptions of being slightly
      overweight or slightly underweight. Students who report 1 or more hours of screen
      or phone time per day were also more likely to be susceptible. This is the first
      study to identify that susceptibility to future smoking among never smokers is
      associated with physical activity, overweight and concerns about weight. This is
      valuable new insight for tailoring and targeting future school-based tobacco
      control and/or physical activity programming to youth populations.

PMID- 18324571
TI  - Waterpipe-associated particulate matter emissions.
AB  - Waterpipe tobacco smoking is increasingly common worldwide, and evidence about
      its harmful effects to smokers is emerging. However, no studies have investigated
      the potential exposure of nonsmokers to waterpipe smoke. We measured particulate
      matter (PM) emissions (PM2.5, PM10) before and during laboratory sessions in
      which 20 individuals used a waterpipe to smoke tobacco and 20 individuals smoked
      a cigarette (10 for each particle-size/smoking-method), as well as 10 waterpipe
      and 10 cigarette smoldering sessions (i.e., without a smoker). A TSI-SidePak
      aerosol monitor obtained PM2.5, PM10 background, smoking, and maximum levels.
      Mean PM2.5 rose 447% for waterpipe (from 48 microg/m3 background to 264 microg/m3
      smoking), and by 501% for cigarettes (from 44 microg/m3 to 267 microg/m3),
      whereas mean PM10 rose by 563% for waterpipe (from 55 microg/m3 to 365
      microg/m3), and by 447% for cigarettes (from 52 microg/m3 to 287 microg/m3)
      (p<.05 for all). The increase in PM during cigarette smoking was due primarily to
      PM2.5, given that the proportion of PM2.5 from total PM10 increase was 95%
      compared with 70% for waterpipe (p<.05). Maximum PM2.5 was 908 microg/m3 for
      waterpipe and 575 microg/m3 for cigarettes, whereas maximum PM10 was 1052
      microg/m3 for waterpipe and 653 microg/m3 for cigarettes. Mean PM2.5 and PM10
      smoldering levels did not differ from background for waterpipe but were
      significantly higher for cigarettes (PM2.5: 33-190 microg/m3; PM10: 42-220
      microg/m3). Policymakers considering clean air regulations should include
      waterpipe tobacco smoking, and the public should be warned about this source of
      smoke exposure.

PMID- 18324570
TI  - Dimensions of depressive symptoms and smoking cessation.
AB  - Because different psychopathologic components of depressive symptoms may have
      distinct etiologies, examining their differential effects on smoking cessation
      may elucidate mechanisms underlying the smoking-depression relationship. Negative
      affect (NA), somatic features (SF), low positive affect/anhedonia (PA), and
      interpersonal disturbance (IP) have been identified as unique dimensions of
      depression that can be measured using the Center for Epidemiologic Studies
      Depression Scale (CESD). This study examined common and unique associations
      between CESD subscales and baseline smoking characteristics, nicotine withdrawal,
      and relapse in 157 participants enrolled in a smoking cessation trial for heavy
      social drinkers. Each dimension was univariately associated with negative and
      positive reinforcement smoking motives. Only SF had unique relations with
      tolerance smoking motives and univariate associations with nicotine dependence
      severity. Only PA predicted cessation-related changes in withdrawal symptoms on
      quit day. Analyses predicting abstinence at 8, 16, and 26 weeks post quit date
      showed that NA, SF, and PA each univariately predicted relapse, ps< or =.0083.
      Only low PA predicted poorer outcomes incrementally to the other dimensions, even
      when controlling for level of nicotine dependence, smoking frequency, and history
      of major depression, p = .0018. Interventions targeting anhedonia and low
      positive affect may be useful for smokers trying to quit.

PMID- 18324572
TI  - Association between cigarette smoking and C-reactive protein in a representative,
      population-based sample of adolescents.
AB  - Although related to inflammatory markers in adults, little is known about the
      association between cigarette smoking and C-reactive protein (CRP) in adolescent
      smokers. We examined the association between high-sensitivity CRP (hs-CRP)
      concentrations and smoking in youth. We used data from a cross-sectional,
      province-wide survey of a representative sample of youth conducted in Quebec,
      Canada, in 1999. Data were collected in self-report questionnaires completed by
      participants and their parents. Participants provided a fasting blood sample, and
      anthropometric measures were undertaken by trained technicians. The present
      analysis pertains to 1,501 adolescents aged 13 and 16 years who completed
      questionnaires and for whom blood samples were available. The independent
      association between a six-category indicator of smoking status and elevated hs
      CRP, defined as a value at least in the 90th percentile of the age- and sex
      specific CRP distribution, was assessed in multiple logistic regression analyses
      controlling for potential confounders. Relative to never-smokers, the odds ratios
      (95% confidence intervals) for puffers (i.e., never smoked a whole cigarette),
      those who smoked but not in the past month, light past-month smokers, moderate
      past-month smokers, and heavy past-month smokers were 1.04 (0.55-1.98), 1.76
      (1.06-2.94), 1.39 (0.70-2.76), 2.07 (0.96-4.42), and 2.40 (1.18-4.88),
      respectively. Our data suggest a positive association between smoking status and
      elevated CRP in adolescents, and in particular among heavier past-month smokers.
      Damage related to cigarette smoking may begin soon after tobacco use initiation,
      reinforcing the preventive message that no level of smoking is safe in youth.

PMID- 18324573
TI  - Longitudinal study of household smoking ban adoption among households with at
      least one smoker: associated factors, barriers, and smoker support.
AB  - We conducted a longitudinal study among Oregon households with at least one
      smoker to assess smoking-related associations with ban adoption, to examine
      smoker support for bans, and to examine barriers to ban establishment. We
      followed a cohort of 1,604 baseline survey respondents for a median time of 21
      months and re-interviewed 825 respondents (51.4% response rate). Of these, 512
      did not have a full household ban in place at baseline. Thirty-two percent of the
      respondents without a ban at baseline adopted a full ban. Baseline smoking
      related factors associated with ban adoption were: longer time until first
      cigarette, stage of change, and attitudes towards respondent's smoking.
      Associated follow-up factors included cessation and reduced consumption. Ninety
      one percent of respondents reported smoker support of a ban. Future work should
      focus on ban establishment in households with more highly addicted smokers.

PMID- 18324574
TI  - The impact of carotid plaque screening on motivation for smoking cessation.
AB  - Showing smokers their own atherosclerotic plaques might increase motivation for
      smoking cessation, since they underestimate their own risk for smoking-related
      diseases. To assess the feasibility and optimal processes of studying the impact
      of carotid atherosclerotic plaque screening in smokers, we enrolled 30 daily
      cigarette smokers, aged 40-70 years, in an observational pre-post pilot study.
      All smokers underwent smoking cessation counseling, nicotine replacement therapy,
      a carotid ultrasound, an educational tutorial on atherosclerosis, baseline and 2
      month motivation to change assessment, and assessment of smoking cessation at 2
      months. Participants had a mean smoking duration of 34 years (SD = 7). Carotid
      plaques were present in 22 smokers (73%). Between baseline and 2 months after
      plaque screening, motivation for smoking cessation increased from 7.4 to 8.4 out
      of 10 (p = .02), particularly in those with plaques (7.2 to 8.7, p = .008). At 2
      months, the smoking quit rate was 63%, with a quit rate of 73% in those with
      plaques vs. 38% in those without plaques (p = .10). Perceived stress, anxiety,
      and depression did not increase after screening. 96% of respondents answered
      correctly at least 80% of questions regarding atherosclerosis knowledge at
      baseline and after 2 months. In conclusion, studying the process of screening for
      carotid plaques for the purpose of increasing motivation for smoking cessation,
      in addition to counseling and drug therapy for smoking cessation in long-term
      smokers, appears feasible. The impact of carotid plaque screening on smoking
      cessation should be examined in larger randomized controlled trials with
      sufficient power to assess the impact on long-term smoking cessation rates.

PMID- 18324575
TI  - Exposure to secondhand smoke in Germany: air contamination due to smoking in
      German restaurants, bars, and other venues.
AB  - This study quantified exposure to secondhand smoke in German restaurants, bars,
      and entertainment venues by determining the concentration of respirable suspended
      particles measuring 2.5 microm or less (PM2.5) in indoor air. The measurements
      were taken using an inconspicuous device placed on the investigator's table in
      the venue. The concentration of particulate matter in the indoor air was measured
      for a minimum of 30 min. A total of 39 restaurants, 20 coffee bars, 12 bars, 9
      discotheques, and 20 restaurant cars in trains were visited throughout Germany
      from September 30 to October 31, 2005. The readings disclosed a median PM2.5 of
      260 microg/m3 and an arithmetic mean PM2.5 of 333 microg/m3. Median values were
      378 microg/m3 in bars, 131 microg/m3 in cafes, and 173 microg/m3 in restaurants.
      The highest medians were measured in discotheques and restaurant cars, with
      values averaging 432 microg/m3 and 525 microg/m3 PM2.5, respectively. This study
      was the first to show the magnitude and extent of exposure to secondhand smoke on
      such an extensive scale in Germany. The contaminated air due to smoking is a
      human carcinogenic and major health hazard, which would be prevented most
      effectively and completely by implementing a ban on smoking. This study is
      important for the ongoing national debate in Germany as well as for debates in
      all countries without smoke-free air legislation, which includes most countries
      around the world.

PMID- 18324576
TI  - [Tissue engineering--update].

PMID- 18324577
TI  - [Clinical applicability of evidence-based orthopedics--a cross-sectional study of
      the quality of orthopedic evidence].
AB  - INTRODUCTION: The demand to routinely apply evidence-based methods in orthopedic
      surgery increases steadily. In order to do so, however, the validity and
      reliability of the "evidence" has to be scrutinized. AIM: The object of this
      study was to assess the quality of the most recent orthopedic evidence and to
      determine variables that have an influence on quality. METHOD: All 2006
      controlled trials from orthopedic journals with high impact factors were analysed
      in a cross-sectional study. A score based on the CONSORT statement was used to
      assess study quality. Selected variables were tested for their influence on the
      quality of the study. RESULTS: Two independent blinded observers reviewed 126
      studies. The overall quality was moderate to high. The most neglected parameters
      were power analysis, intention-to-treat, and concealment. The participation of a
      methodologically trained investigator increases study quality significantly.
      There was no difference in study quality irrespective of whether or not there was
      statistically significant result. CONCLUSION: Using our quality score we were
      able show fairly good results for recent orthopedic studies. The most frequently
      neglected issues in orthopedic research are blinding, power analysis, and
      intention-to-treat. This may distort the results of clinical investigations
      considerably and, especially, lack of concealment causes false-positive findings.
      Our data show furthermore that participation of a methodologist significantly
      increases quality of the study and consequently strengthens the reliability of
      results.

PMID- 18324578
TI  - [Tissue engineering in orthopaedic surgery--clinical effectiveness and cost
      effectiveness of autologous chondrocyte transplantation].
AB  - BACKGROUND: Tissue engineering applications are spreading in orthopaedic surgery.
      The best known example is autologous chondrocyte transplantation (ACT). The
      objective of this work is to compare ACT with alternative treatment options
      concerning long-term effects and cost-effectiveness. MATERIAL AND METHODS: Data
      on clinical effectiveness, long-term effects, and cost-effectiveness are
      systematically reviewed. Due to the high clinical and statistical heterogeneity
      between studies a descriptive analysis has been done. RESULTS: 6 randomised
      controlled studies have assessed the effectiveness of ACT compared with
      microfrature or mosaic plasty. 4 studies report on no or only insignificant
      differences - one recently presented 5-year results - whereas 2 studies observed
      better results with ACT. Long-term results are good throughout, but the high
      quality of the regenerative tissue is a clear advantage of ACT. Cost
      effectiveness models support ACT for the longevity of its results and thus
      relatively lower costs in the long-term. CONCLUSION: ACT is an expensive and
      complex procedure. In direct comparison with alternative treatments ACT produces
      results at least as good in the short-term, and most likely better in the long
      term due to the high quality repair tissue. Thus higher initial costs are
      compensated for with time.

PMID- 18324579
TI  - [Clinical results after three years use of matrix-associated ACT for the
      treatment of osteochondral defects of the knee].
AB  - AIM: The aim of this study was to examine the clinical results after the
      treatment of osteochondral defects of the knee with autologous bone grafting and
      matrix-supported autologous chondrocyte transplantation (ACT). METHOD: In this
      study 13 patients with osteochondral defects of the knee (12 femoral, 1 tibial)
      with OCD ICRS grade IV or ICRS grade IV B were included. The osteochondral
      defects were reconstructed simultaneously with autologous monocortical cancellous
      bone cylinders or chips from cancellous bone and matrix-supported autologous
      chondrocyte transplantation (CaReS). Data were analysed in accordance with the
      ICRS criteria and the Brittberg score. Patients were followed up to 36 months
      after the operation. RESULTS: The average age of the patients was 34.9 (16 - 47)
      years at the time of surgery. The size of the defect was 8.1 (3.8 - 13.5) cm(2).
      The subjective and objective IKDC scores, the Brittberg and the ICRS function
      score were statistically significantly improved during the observation time. In
      one patient the transplantation failed and another patient was not available for
      the follow-up at 36 months. The objective IKDC score and the ICRS function score
      increased from 0/13 (0 %) to 11/12 (91.7 %) in categories A and B, or I and II,
      respectively, after 3 years. At this point of time 83.4 % (10/12) of the patients
      voted the treatment as excellent or good. The subjective IKDC score improved from
      38.4 (+/- 12.7) preoperatively to 66.1 (+/- 17.0) after 3 years. CONCLUSION: The
      treatment of osteochondral defects of the knee with autologous bone grafting and
      matrix-supported autologous chondrocyte transplantation shows promising results
      even for larger defects. But for a final decision about this therapy the present
      sample size was too small. There is a need for further long-term investigation
      with a larger number of patients.

PMID- 18324580
TI  - [What is the value of the whole body spiral CT in the primary radiological
      imaging of severely injured children?].
AB  - AIM: Whole body spiral CT scans have become a routine method in the radiological
      imaging of severely injured patients in emergency rooms of an increasing number
      of hospitals. The routine use of CT scans is, however, still discussed
      controversially, especially with regard to its use in children. This is mainly
      due to the reportedly higher level of exposure to radiation of CT scans as
      compared to plain radiographs. The aim of the present study was to compare the
      dose of exposure to radiation of a whole body CT scan to that of a plain
      radiograph protocol in an animal model for severely injured children. MATERIAL
      AND METHODS: We chose 3 female pigs of different weights to serve as a model for
      children at different ages. 4 film radiation dosimeters (positioned on the eye,
      under the breast, paravertebrally on the thoracic spine and in the small pelvis,
      respectively) were implanted into every pig for each examination. Plain
      radiographs of the chest and the pelvis in one plane and of the skull and the
      complete spine in two planes were performed. The CT scan included skull, cervical
      spine and the whole body from the thorax to pelvis. RESULTS: The radiation dose
      of CT scans was 7 times higher as compared to the X-ray protocol, but the
      performance of CT scans was faster (8 vs. 18 min). The radiation dose of the
      whole body CT scan was at about 15 mSv. CONCLUSION: Based on our data and a
      review of the literature we will use whole body spiral CT scans as the preferred
      method in the primary radiological imaging of severely injured patients. In our
      opinion, the evident benefit of a reduced time of imaging in combination with
      superior image information outweighs the higher level of exposure to radiation.

PMID- 18324581
TI  - [Surgical outcome in pertrochanteric femur fracture: the impact of osteoporosis.
      Comparison between DHS and percutaneous compression plate].
AB  - AIM: The dynamic hip screw (DHS) often shows an impared outcome and a high
      incidence of therapeutic failure in patients with osteoporotic pertrochanteric
      femur fractures. This is caused predominantly by a fracture collapse and appears
      often in unstable fractures (31A2, 31A3). In a prospectively documented clinical
      study, we examined whether or not the percutaneous compression plate (PCCP,
      Gotfried) offers advantages following osteoporotic fractures. METHOD: From August
      2003 to December 2005, 103 patients underwent internal fixation with the DHS (n =
      40, age 76.1, ASA 2.9) or with the PCCP (n = 63, age 76.9, ASA 2.8). Proximal
      femurs were classified with the Singh grading system, which uses six grades of
      trabecular patterns to describe the degree of osteoporosis. Reexamination of the
      patients (27 DHS, 43 PCCP) was performed on average 18 months later. RESULTS: The
      PCCP was implanted into very osteoporotic femurs (Singh 2) in less time than the
      DHS (47 vs. 79 min). These patients treated with PCCP showed no difference in
      blood loss, but tended to have better outcomes (Merle d'Aubigne, Harris hip
      score) than those treated with DHS. Life quality, subjectively measured with the
      visual analogue score, was significantly better in the PCCP group with high-grade
      osteoporosis (Singh 2). The outcome after implantation of the PCCP was not
      correlated to the Singh index in stable or in unstable fractures. Mechanical
      complications occurred especially in unstable fractures (re-operation rate: DHS
      4/18 [22 %], PCCP 3/29 [10 %], p = 0.266), without correlation to the Singh
      index. Excluding the avoidable complication of loosening of the screw-barrel
      portion, the re-operation rate for the PCCP was 3 % (cut-out: 1/29, p = 0.042) in
      unstable fractures. CONCLUSION: Use of the minimally invasive PCCP technique in
      osteoporotic pertrochanteric femur fractures provides an alternative to the
      dynamic hip screw, especially with regard to surgical time and outcome.
      Advantages occurred also in the re-operation rate following fracture fixation
      complications. The cut-out rate was significantly lower than in the DHS group in
      unstable fractures.

PMID- 18324582
TI  - [Evaluation of a strategy for the management of accompanying osteoporosis after
      inpatient treatment of fragility fractures].
AB  - AIM: The aim of the present study was to evaluate a strategy for the management
      of accompanying osteoporosis after inpatient treatment of fragility fractures.
      METHOD: A prospective group of patients that was treated for acute fragility
      fractures between 9/05 and 2/06 was informed about a concomitant osteoporosis
      according to the national guidelines. Standardised letters with instructions for
      diagnostics and therapy for osteoporosis were given to patients, members of the
      family and outpatient care, rehab-clinic and GPs. Between 9/04 and 2/05 a
      retrospective review of a control group of patients with acute fragility
      fractures was conducted. This group was not informed about a concomitant
      osteoporosis. A telephone survey of all patients for analysis of the management
      of osteoporosis was conducted one year after clinical treatment. RESULTS: Both
      groups were comparable according to numbers of patients, age, distribution
      between the sexes and fracture localisation. The prospective group consisted of
      144 patients. 29.9 % of these patients had already sustained a fragility fracture
      before treatment of the current fracture. In 45.8 % (32.6 % DEXA scans, 11.8 % Q
      CT, 1.4 % ultrasound) of the patients diagnostics were performed. A diagnosis of
      osteoporosis was documented in 42.4 % of the patients, and 57.1 % of the patients
      received specific treatments according to the guidelines. In the control group,
      28.9 % of the patients had already sustained a fragility fracture before
      treatment of the current fracture. In 91.1 % of the patients no diagnostics for
      concomitant osteoporosis after clinical treatment for the acute fracture were
      performed within one year after fracture treatment. CONCLUSIONS: By use of a
      multifaceted osteoporosis intervention, more patients received diagnostics and
      therapy according to the guidelines of osteoporosis after fragility fractures.
      Without appropriate information, more than 60 % of the high-risk-patients did not
      receive adequate osteoporosis management. Future research should address barriers
      to appropriate osteoporosis management. Because of the chronic character of the
      disease and the necessity of a long-term therapy, continuous medical care and
      information of patients with osteoporosis is necessary to prevent subsequent
      fractures.

PMID- 18324583
TI  - [Therapy effects of testosterone on the recovery of bone defects].
AB  - AIM: Androgens have proliferative effects on osteoblasts and increase fracture
      healing by systemic and local stimulation of bone formation. The aim of the
      present study was to evaluate if the systemic stimulation by androgens leads to
      increased bone-defect healing. METHODS: 1.5-mm trepanation defects were created
      in the femoral diaphysis of 30 Sprague-Dawley rats. 10 animals were used as
      untreated controls and 10 animals per group were treated by intramuscular
      injection of 1 or 10 mg dihydrotestosterone two days prior to surgery. After 14
      days the samples were explanted and examined by macroscopy, histology and
      histomorphometry. RESULTS: All animals were included into the study and were
      analysed. Clinical observation showed no complications. Macroscopic examination
      and histology showed no significant differences. All defects were filled with
      trabecular bone in direct contact to the surrounding bone. Histomorphometry
      showed a significantly decreased bone content in the controls in comparison to
      both therapy groups, while the therapy groups showed no significant differences
      between each other. CONCLUSION: The stimulation of healing of bone defects with
      androgens leads to a significantly higher bone content inside the defects. In
      clinical application, androgens may be a possibility to increase bone formation,
      especially in elderly patients. Furthermore, it may be possible to shorten
      postoperative rehabilitation because of the effects of androgens on muscles.

PMID- 18324584
TI  - [Animal study of the bone substitute material Ostim within osseous defects in
      Gottinger minipigs].
AB  - AIM: The aim of this study was to examine Ostim, a nanocrystalline hydroxyapatite
      suspension, with regard to its bio- and osteocompatibility, rate of resorption
      and remodeling dynamics within osseous defects. METHODS: Ostim was implanted in a
      randomised fashion into the proximal metaphysis of either the right or the left
      tibia of 18 Gottinger minipigs. RESULTS: Based on microradiographs and
      histological examinations Ostim showed biocompatibility, bioactivity and
      osteoconductivity. This substitute material exhibited osseous integration. The
      degradation process stopped after six weeks. With regard to osseous regeneration
      within the defects, there were no significant differences between the time
      intervals of follow-up. Ostim could still be detected in significant amounts
      after one year with no complete resorption. CONCLUSION: A restitutio ad integrum
      could not be observed in spite of the histological evidence of the above
      described reactions within the implantation site. A thorough osseous
      incorporation seemed to impede the degradation of the bone substitute material.
      The paramount goal is to improve the biological behaviour in favour of a higher
      rate of degradation.

PMID- 18324585
TI  - [Percutaneous lumbar interbody fusion using autogenous osteoblasts in vivo].
AB  - AIM: In the present study we have investigated the potential of autogenous
      osteoblasts for osteoinduction in a spinal arthrodesis model. METHOD: After
      posterolateral instrumentation of 3 segments of a sheep spine the intervertebral
      space was filled with cancellous bone, osteoblasts or left empty after nucleotomy
      and elimination of cartilage. RESULTS: Radiological and histological analyses
      proved a significant osseous reaction in segments treated with cancellous bone or
      osteoblasts in contrast to the control segment. This outcome provides evidence of
      spondylodeses by spinal instrumentation in combination with osteoblasts in a
      sheep model. CONCLUSION: The results suggest a possible application of autologous
      osteoblasts as an osteoinductor after percutaneous nucleotomy in spinal fusion.
      The possible application in a human model should be examined.

PMID- 18324586
TI  - [Conservative treatment of lumbar spinal stenosis--a review].
AB  - AIM: The aim of this study is to provide an analysis of the literature and our
      own experience in the conservative treatment of lumbar spinal stenosis. Although
      lumbar spinal stenosis is treated mostly non-operatively there are only a few
      reports in the literature about the results of conservative treatment. All the
      recent articles about surgical procedures for LSS mention ineffective
      preoperative treatment without explaining it. So far there have been no
      randomised clinical trials to obtain evidence regarding the clinical outcome of
      non-surgical management. METHOD: We provide an actual overview about the
      conservative treatment of LSS referring only to retrospective studies, guidelines
      and expert opinions. Solely the treatment of LSS with epidural steroids, which is
      recommended by most of the authors, has been evaluated by several randomised
      controlled studies with a high level of evidence. RESULTS: As far as we can
      summarise at present, a multidisciplinary conservative treatment programme is
      most effective not only for discogenic low-back pain but also for LSS with a
      concentration on physiotherapy, behavioural therapy, epidural injections and a
      special back training which is presented in this paper. CONCLUSION: Patients with
      LSS should receive a trial of the proposed conservative, aggressive treatment
      before surgery is considered.

PMID- 18324587
TI  - [Lapidus procedure in patients with rheumatoid arthritis--short-term results].
AB  - AIM: Hallux valgus combined with flat foot is one of the most common foot
      deformities affecting patients with rheumatoid arthritis. The Lapidus procedure
      is indicated when the hallux valgus angle is more than 15 degrees or the first
      tarsometatarsal joint is hypermobile. We aimed to evaluate the results of the
      Lapidus procedure in patients with rheumatoid arthritis. METHOD: We performed the
      Lapidus procedure in 31 patients between 2002 and 2005. In ten patients we
      performed a bilateral procedure and in ten patients we performed a single Lapidus
      procedure. In 27 cases we combined the procedure with a resection of the second
      fifth metatarsal heads (Hoffmann procedure), in four cases with a Weil osteotomy
      of the second-fifth metatarsal necks. We performed an excision of the articular
      surface of the first metatarsal head (Mayo) in 10 patients, a Keller resection
      procedure in 9 patients, an arthrodesis of the first metatarsophalangeal joint in
      3 patients, and an Akin wedge osteotomy of the proximal phalanx of the thumb in 3
      patients. Arthrodesis was fixed by two K-wires in 5 cases, by 2 compression
      screws in 7 cases, and in thirty-four cases we used memory staples. RESULTS: We
      evaluated the outcomes of forty-one procedures in thirty-one patients (24 female,
      7 male). The averge age at surgery was 54.3 years. Thirty-two feet were without
      pain after the procedures, in five cases the patients felt moderate pain in the
      dorsal part of the foot and in four cases the patients felt pain in the
      transverse arch of foot. Complications included delayed primary wound closure in
      five cases, in one case we performed a revision procedure for a deep infection.
      Delayed hallux valgus developed in 5 cases. The mean first intermetatarsal angle
      before surgery was 19.5 degrees (range 12 - 27 degrees) and improved to 8 degrees
      after surgery. In 3 cases we found an unsatisfactory intermetatarsal angle
      correction with partial renewal of the hallux valgus. CONCLUSION: A correctly
      performed Lapidus procedure enables correction of the varus position of 1st
      metatarsus and hallux valgus.

PMID- 18324588
TI  - [Loading of the tibiotalar joint and Chopart's joint following subtalar
      arthrodesis: dynamic cadaver study of 5 specimens].
AB  - AIM: Little has been known until now about biomechanical intra-articular changes
      in the condition of adjacent joints following subtalar arthrodeses. METHOD: We
      tested 5 cadaver specimens in a dynamic axially loaded foot model under computer
      regulated load application on 9 extrinsic tendons of the foot regarding changes
      in load under native conditions and following an anatomically fixed subtalar
      arthrodesis. RESULTS: We saw an averaged native force transmission in the
      talonavicular joint of 87 N, increasing post-arthrodesis to 92 N. In the
      calcaneocuboid joint we measured an increase from 72 N to 74 N. For peak
      pressure, the increase was from native 3152 kPa to 3286 kPa in the talonavicular
      joint and in the calcaneocuboid joint we recorded a reduction from 3282 kPa to
      3277 kPa. The effects are not striking from a statistical viewpoint. However, we
      observed a reduction in force from native 103 N to 90 N and in peak pressure from
      4778 kPa to 4261 kPa in the ankle. When the ankle was divided into discrete zones
      in the sagittal and frontal planes there was no evidence of load displacement.
      CONCLUSION: Our measurements show that anatomically fixed arthrodeses of the
      talocalcanear joint do not lead to any striking increase in loads on adjacent
      joints. Any adjacent segment degeneration following subtalar arthrodeses may be
      the result of changes in joint kinematics or non-anatomically reconstructed
      hindfoot positions.

PMID- 18324589
TI  - [Elution kinetics and antimicrobial effects of gentamicin- and clindamycin-loaded
      bone cements in vitro].
AB  - AIMS: In arthroplasty and particulary in revision surgery antibiotic-loaded bone
      cements are applied. The purpose of the current study was to analyse the kinetics
      of antibiotic release and antimicrobial effects of the gentamicin- and
      clindamycin-loaded bone cement Versabond. MATERIALS AND METHODS: Test cylinders
      of bone cements, containing gentamicin and clindamycin in different
      concentrations, were investigated in vitro with regards to the kinetics of
      antibiotic release by applying static and continuous elution methods.
      Antimicrobial effects of antibiotic-loaded bone cement were tested in an
      infection model with different strains of Staphylococcus aureus and
      Staphylococcus epidermidis and live/dead dye plus fluorescence microscopy. For
      the surface analysis of antibiotic-loaded test cylinders contaminated with
      Staphylococcus epidermidis, scanning electron microscopy was used. RESULTS: The
      measurement of static and continuous elution revealed initially higher rates of
      gentamicin release in comparison with clindamycin. The gentamicin amount
      decreased within 24 h, whereas clindamycin-loaded test cylinders showed a
      prolonged release. After 24 h exclusive avital bacteria on antibiotic-loaded
      cement cylinders were seen, after 72 h on gentamicin-loaded cement bacterial
      growth was again detected. Application of antibiotics in bone cement revealed an
      inhomogeneous surface of the bone cement cylinder. CONCLUSIONS: On application of
      clindamycin in bone cement the features of increased antibiotic uptake and
      antimicrobial effect compared with gentamicin-loaded bone cement are observed.

PMID- 18324590
TI  - [Mechanical bending strength of explanted ex vivo bone cements compared with in
      vitro samples].
AB  - INTRODUCTION: The mechanical properties of acrylic bone cements are an important
      factor in determining an efficient load transmission between prosthesis and bone
      to guarantee the long-term stability in cemented hip arthroplasty. MATERIAL AND
      METHODS: Palacos and Refobacin Palacos specimens from 21 aseptically loosened
      femoral compoments of cemented hip arthroplasties manufactured by the first to
      third generation cementing technique have been mechanically tested in a
      standardised four-point bending test (ISO 5833). In vitro manufactured Palacos
      and Refobacin Palacos specimens served as a control group. The fatigue fracture
      surfaces were morphologically analysed with light microscopy. RESULTS: Under in
      vitro conditions manufactured specimens had higher values of bending strength,
      with the exception of blood contaminated ones, compared to ex vivo specimens. Ex
      vivo specimens of the second and third generation cementing technique had higher
      values than specimens of the first generation. CONCLUSIONS: Acrylic bone cements
      are subjected to a multifactorial material fatigue in vivo. Here, the art and
      quality of cementing technique is of eminent importance in determining the long
      term stability of cemented hip arthroplasty.

PMID- 18324591
TI  - [In vitro studies on various PMMA bone cements: a first comparison of new
      materials for arthroplasty].
AB  - AIM: Two clinically established PMMA bone cements (Refobacin Palacos R and
      Palacos R + G) and two newer cements not yet in widespread clinical use
      (Refobacin Bone Cement R and SmartSet GHV) were tested in vitro for practically
      relevant differences. METHODS: The tests included chemical analyses, handling
      properties and testing according to the ISO standard for PMMA bone cements.
      RESULTS: The results obtained indicate clearly that the copolymers used in
      Refobacin Bone Cement R and SmartSet GHV differ from those used in the Palacos
      cements. There were also significant differences in viscosity behaviour and
      waiting time (p < 0.01 for Palacos cements versus Refobacin Bone Cement R) as an
      expression of different handling properties. The hardening times under ISO 5833
      conditions also differed significantly (p < 0.01 and p < 0.05 for Palacos cements
      compared with Refobacin Bone Cement R and p < 0.01 for Refobacin Bone Cement R
      compared with SmartSet GHV). CONCLUSION: In view of these differences in material
      properties, the clinical data from long-term use of the bone cements Refobacin
      Palacos R and Palacos R + G cannot be extrapolated to the newly developed PMMA
      cements Refobacin Bone Cement R and Smart GHV. Before broad clinical use of these
      cements, prospective clinical studies using RSA or DEXA and, as a second step,
      statistically powerful prospective comparative studies should be performed. Until
      these data are available, patients in whom Refobacin Bone Cement R and SmartSet
      GHV are used should be informed that the material employed deviates from the
      standard procedures for cemented joint replacement in the Scandinavian
      arthroplasty registers and that the long-term consequences cannot, in the final
      instance, be foreseen. This is essential in order to avoid later malpractice
      claims on the grounds of inadequate information.

PMID- 18324592
TI  - [Femoral neck fractures].

PMID- 18324594
TI  - Scintigraphy of benign bone disease.
AB  - Bone scintigraphy is ideally suited for the investigation of benign bone disease
      as it functions at a physiological level. It is freely available and has whole
      body capability and high-contrast resolution. When coupled with single-photon
      emission computed tomography/computed tomography (SPECT/CT), it can be utilized
      to provide precise anatomical localization, attenuation correction, and therefore
      better lesion localization. A considerable volume of data has accumulated on the
      role of bone scintigraphy in trauma and its complications, overuse injuries,
      vascular disease of bone, metabolic bone diseases, and a variety of other
      disorders. This article is an overview of the established applications and
      signposts of potential future applications with the increasing prevalence of
      SPECT/CT devices and technical advances in attenuation correction, collimator
      modeling, and resolution recovery software.

PMID- 18324595
TI  - The current status of bone scintigraphy in malignant diseases.
AB  - For the past few decades, planar bone scintigraphy has been the most frequently
      performed imaging study in the evaluation of metastatic bone disease. Although
      scintigraphic findings alone are often nonspecific for skeletal pathologies, this
      technique reportedly has an exquisite sensitivity. However, recently accumulated
      data on the efficacy of positron emission tomography with fluorine-18
      fluorodeoxyglucose and fluorine-18 sodium fluoride as well as magnetic resonance
      imaging for evaluating skeletal metastatic disease now indicate that conventional
      planar bone scintigraphy is not very sensitive in the detection of metastatic
      bone lesions in selected malignancies. Nevertheless, bone scintigraphy still
      remains the primary imaging modality for evaluation of metastatic bone disease
      owing mainly to its cost effectiveness and wide availability. In addition,
      recently introduced hybrid imaging systems combining single-photon emission
      computed tomography and spiral computed tomography, although not widely available
      yet, increase considerably both the sensitivity and specificity of bone
      scintigraphy. This article focuses primarily on the current role of bone
      scintigraphy and its strengths and weaknesses in assessing different types of
      malignant diseases relative to other imaging modalities in selected malignancies.

PMID- 18324596
TI  - PET/CT in malignant bone disease.
AB  - The most commonly used positron emission tomography (PET) tracer in clinical
      practice, fluorine-18 fluorodeoxyglucose ( (18)F-FDG) is a glucose analogue that
      directly gains entry in excess into tumor cells. It is therefore sensitive for
      the detection of early bone marrow involvement prior to any identifiable bone
      changes. The introduction of (18)F-FDG-PET in the imaging algorithms of various
      malignant diseases often obviates the need to perform a separate assessment of
      malignant bone involvement with conventional bone scintigraphy. After therapy,
      disappearance of (18)F-FDG accumulation indicates success even when the bone
      remains morphologically abnormal. Novel hybrid systems composed of PET and
      computed tomography (CT) allow for acquisition of both modalities in the same
      clinical setting and the generation of fused functional-anatomical images. This
      technique has been found to improve the diagnostic accuracy of PET in detecting
      malignant bone involvement. This article discusses the role of PET/CT, primarily
      (18)F-FDG PET/CT, in the assessment of malignant bone involvement in patients
      with primary bone sarcomas, common solid malignancies, lymphoma, and multiple
      myeloma.

PMID- 18324597
TI  - Pediatric musculoskeletal nuclear medicine.
AB  - This article reviews the current role of nuclear medicine in common benign and
      malignant pediatric musculoskeletal conditions and discusses future applications.

PMID- 18324598
TI  - Radionuclide imaging of musculoskeletal infection: conventional agents.
AB  - The diagnosis of musculoskeletal infection can be clinically challenging, and
      radionuclide imaging is often performed as part of the diagnostic workup.
      Conventional studies include bone scan, gallium imaging, and labeled leukocyte
      imaging. No single test is equally efficacious in all situations, and thus the
      procedure(s) performed should be optimized for the individual patient. Three
      phase bone imaging, readily available and relatively inexpensive, is very
      accurate in unviolated bone. In the setting of underlying osseous abnormalities,
      however, the specificity of the test decreases. Four-phase bone, sequential
      bone/gallium, and labeled leukocyte imaging all have been used in an effort to
      enhance specificity. Labeled leukocyte imaging is the radionuclide procedure of
      choice for diagnosing so-called complicating osteomyelitis such as infected joint
      prostheses, diabetic pedal osteomyelitis, and infection of the neuropathic joint.
      To maximize the accuracy of the study, complementary bone marrow imaging often
      must be performed. Labeled leukocyte imaging is of limited value in spinal
      osteomyelitis, however, because this entity often presents as a nonspecific
      photopenic defect on white cell studies. The conventional radionuclide study for
      evaluating spinal osteomyelitis is gallium imaging, which should be performed
      regardless of the findings on a contemporaneous bone scan. The reasons for this
      are as follows: Gallium improves the specificity of the bone scan; gallium
      detects accompanying soft tissue infection, whereas the bone scan does not, and
      gallium may be more sensitive than the bone scan in elderly patients.

PMID- 18324599
TI  - PET/CT in musculoskeletal infection.
AB  - Early diagnosis of musculoskeletal infections is the key to successful therapy
      and prevention of complications. Fluorine-18 (F-18) fluorodeoxyglucose-positron
      emission tomography (FDG-PET) is a promising modality for imaging musculoskeletal
      infection and might play an important role in the evaluation of chronic
      osteomyelitis and spinal infection. FDG-PET has shown promising results for
      diagnosing both acute and chronic infection of the axial and appendicular
      skeletons. PET imaging will have increased importance in patients with metallic
      implants because FDG uptake, in contrast to magnetic resonance imaging (MRI) and
      computed tomography (CT), is not hampered by metallic artifacts. In patients with
      suspected prosthetic joint infection, results of PET are controversial, and
      combined indium-111-labeled leukocyte and technetium-99m-sulfur colloid marrow
      scintigraphy still remains the gold standard. PET/CT with the combination of PET
      and a low-dose or full-dose diagnostic CT provides exact anatomical correlation
      of bone and joint lesions and increases the accuracy of the test compared with
      PET alone. The question of in which situations PET/CT becomes the preferred
      imaging method in suspected musculoskeletal infection depends on several factors,
      including cost and availability. This article reviews the currently available
      literature and addresses the use of FDG-PET/CT in the diagnosis of
      musculoskeletal infections.

PMID- 18324600
TI  - [Chronic pain and fatigue, and the psychiatrist].

PMID- 18324601
TI  - [The effectiveness of anxiety treatment on alcohol-dependent patients with a
      comorbid phobic disorder: a randomised controlled trial].
AB  - BACKGROUND: There is evidence that the post-treatment relapse rate for alcohol
      dependent patients with a comorbid anxiety disorder is higher than for alcohol
      dependent patients without this disorder. aim To discover whether the post
      treatment relapse rate in alcohol-dependent patients who suffer from both alcohol
      dependence and a comorbid anxiety disorder can be lowered by giving them
      additional treatment specifically for the comorbid anxiety disorder. METHOD: A 32
      week randomised controlled trial among 96 abstinent patients with a primary
      diagnosis of alcohol dependence and a comorbid anxiety disorder involving
      agoraphobia or social phobia. The patients were randomly assigned either to an
      intensive psychosocial relapse-prevention programme only (n = 49) or to a
      combined programme in which the aforementioned programme was supplemented by an
      anxiety treatment programme comprising cognitive behavioural therapy and optional
      pharmacotherapy in the form of an SSRI (n = 47). The primary outcome measure was
      the percentage of patients who suffered an alcohol relapse during a 32-week
      period. The secondary outcome measures were: total abstinence, a reduction in the
      number of days of heavy drinking and a reduction in anxiety symptoms. results
      Although the anxiety symptoms in the group receiving cognitive behavioural
      therapy diminished more than in the group not receiving this therapy, the alcohol
      relapse rates in the former group were not significantly lower than in the latter
      group. CONCLUSION: Anxiety treatment for alcohol-dependent patients with a
      comorbid anxiety disorder can alleviate anxiety symptoms but has no significant
      effect on the outcome of alcohol treatment programmes.

PMID- 18324602
TI  - [When is psychosis dangerous? Ethical, professional en juridical considerations
      concerning psychosis and coercion in Belgium].
AB  - BACKGROUND: In Belgium a patient can only be compulsorily admitted to a
      psychiatric hospital if he is a danger to himself or others (law concerning
      coercion in Belgium, 26/06/1990). AIM: To explore the relationship between
      psychosis and danger, and to analyse the various interpretations of the
      'dangerousness' criterion in the context of psychotic disorders and the
      underlying ethical positions. METHOD: We studied the literature by means of
      PubMed, PsycINFO, manuals and references and used the search terms: 'coercion',
      'commitment of mentally ill', 'dangerous behaviour', and 'psychotic disorders'.
      results The correlation between psychosis and danger is limited but is
      strengthened by comorbid substance abuse and non-compliance. The clinical
      assessment of danger does not have a firm scientific basis. The underlying
      ethical position determines when danger is regarded as being serious enough to
      justify coercion. CONCLUSION: Danger is a problematical criterion for coercion.
      We propose a model that weighs up the likelihood of danger against the expected
      pros and contrasts of coercion and the extent to which the disorder can be
      treated. The fluid nature of the 'dangerousness' criterion and the principle of
      proportionality call for a more varied arsenal of coercive measures which are
      less drastic than compulsory admission.

PMID- 18324603
TI  - [Towards deepened psychiatric diagnostics].

PMID- 18324604
TI  - [The beginning psychiatric training syndrome in the year 2007. Myth or reality?].
AB  - The beginning psychiatric training syndrome is a controversial, but imaginative
      nosological concept. This short paper provides a concise overview of the relevant
      literature on beginning psychiatric training syndrome, and presents the results
      of a pilot study regarding health problems among 35 residents in the Netherlands.
      On the basis of the two analyses, it is concluded that, as a rule, health
      problems among this group of doctors tend not to evolve into states of
      psychopathology in the restricted sense. Nonetheless, it is advisable to monitor
      such health problems with a view to their prevention.

PMID- 18324605
TI  - [Pipamperone and the treatment of impulsive aggressive behaviour].
AB  - BACKGROUND: Pipamperone is prescribed to prevent impulsive aggressive behaviour
      in patients with intermittent explosive disorder, personality disorders or mental
      retardation. AIM: To investigate the scientific basis of this treatment. METHOD:
      Various databases were searched using the terms 'pipamperon', 'pipamperone' and
      'Dipiperon'. Located articles were reviewed in order to discover whether they
      dealt with the relationship between the drug and impulsiveness and aggression.
      results Six publications were found, all dating from before 1979. CONCLUSION: In
      view of the limited amount of research on the subject and the adverse side
      effects it is concluded that pipamperone is not the drug of first choice
      considering the treatment of impulsive aggressive behaviour.

PMID- 18324606
TI  - ['My daughter eats my mattress!'--a patient with pica].
AB  - BACKGROUND: For the third time a 17-year-old adolescent is presented to a child
      and adolescent ambulatory mental health clinic, because of eating foam rubber. In
      this case study pica is being discussed and its possible connection with a
      somatic disease (sickle cell anaemia). The importance of alertness to unknown
      symptoms in diagnosing is being underlined, as well as the value of searching for
      a biological explanation in order to prevent interpreting all strange behaviour
      as psychosocial of origin.

PMID- 18324607
TI  - Short-term outcomes following total minimally invasive oesophagectomy.
AB  - BACKGROUND: Minimally invasive oesophagectomy (MIO; thoracoscopy, laparoscopy,
      cervical anastomosis) is a complex procedure and few substantial series have been
      published. This study documented the morbidity, mortality and challenges of
      adopting MIO in a specialist unit in the UK. METHODS: A prospective group of 77
      patients was listed consecutively with the intention of performing MIO. Three
      other patients underwent open oesophagectomy during the study period. RESULTS:
      MIO was attempted in 77 patients, completed successfully in 70, abandoned in six
      patients (8 per cent) with unsuspected metastatic disease, and converted to a
      thoracoscopic anastomosis in one patient. There was one in-hospital death (1 per
      cent). Complications occurred in 33 patients (47 per cent), including nine
      gastric conduit-related complications (13 per cent). Median lymph node harvest
      was 21 (range 7-48) nodes. Mean overall and disease-free survival times were 35
      and 33 months respectively. Median disease-free survival for patients with stage
      III disease was 26 months. CONCLUSION: MIO can be performed with acceptable
      mortality and morbidity rates in an unselected series of patients. There was more
      morbidity related to gastric tube ischaemia than was expected.

PMID- 18324608
TI  - Influence of control selection in nested case-control studies: the example of
      exposure to antiretroviral treatment (ART) and the risk of myocardial infarction
      (MI) in the French Hospital Database on HIV (FHDH-ANRS CO4).
AB  - PURPOSE: Soon after availability of protease inhibitors (PIs), a duration-related
      effect relationship between PI and myocardial infarction (MI) was shown. New
      antiretroviral treatments (ARTs) have allowed more individualized regimens. To
      study their influence established risk factors of MI and additional therapeutic
      options such as lipid-lowering drugs will have to be taken into account. A nested
      case-control is an interesting alternative raising the choice of controls. With
      the previous full cohort analysis as reference, we investigated the influence of
      control selection in nested case-control studies sampled in this cohort by
      testing nine sampling scenarios. METHODS: During the period 1996-1999, 49 MI
      occurred among male patients exposed to PI and followed-up in the French Hospital
      Database on HIV (FHDH-ANRS CO4). For each case, controls were selected using
      incidence-density sampling. The influence of additional matching criteria was
      tested. Random sampling and analysis was repeated 100 times with varying control
      case ratios. RESULTS: When controls were randomly selected among patients of the
      same age who were free of MI at the date MI was diagnosed in the case, we
      observed a duration-related effect relationship between PI and MI in agreement
      with the results of the full cohort analysis. The use of four controls per case
      was sufficient. Estimates obtained with simple sampling were more precise than
      those obtained when controls were also matched for year of enrollment, initial
      CD4 cell count and HIV transmission group. CONCLUSION: To study ARTs as MI risk
      factors, nested case-control using incidence-density sampling without additional
      matching is one appropriate option.

PMID- 18324609
TI  - Metabolite identification of arbidol in human urine by the study of CID
      fragmentation pathways using HPLC coupled with ion trap mass spectrometry.
AB  - The metabolism of arbidol in humans was studied using liquid chromatography
      electrospray ionization (ESI) ion trap mass spectrometry (ITMS) after an oral
      dose of 300-mg arbidol. A total of 17 metabolites were identified including the
      glucuronide arbidol and the glucuronide sulfinylarbidol as the major metabolites.
      Arbidol and its metabolites have some common fragmentation patterns as a result
      of a homolytic bond cleavage. This cleavage will form odd-electron ions with the
      loss of a radical. The arbidol fragmentation sequence is first to lose
      dimethylamine (45 Da), followed by the loss of acetaldehyde (44 Da), and then the
      phenylthio radical (109 Da). This fragmentation sequence is also observed from N
      demethylarbidol, sulfonylarbidol, and N-demethylsulfonylarbidol. However, for
      sulfinylarbidol and N-demethylsulfinylarbidol, the fragmentation sequence is
      reversed so that the phenylsulfiny radical (125 Da) was lost first, followed by
      the loss of dimethylamine (45 Da), and then acetaldehyde (44 Da). The exact
      masses for arbidol and sulfinylarbidol fragment ions were determined by a
      quadrupole/time-of-flight mass spectrometer (Q-TOF MS). The phase II metabolites,
      such as sulfate and glucuronide conjugates of arbidol, N-demethylarbidol,
      sulfonylarbidol, and N-demethylsulfonylarbidol were identified by observing the
      neutral loss of 80 Da (SO(3)) or 176 Da (glucuronic acid) from the MS(2) spectra.
      The sulfate and glucuronide conjugates such as sulfinylarbidol and N
      demethylsulfinylarbidol had an unusual fragmentation pattern, in which the
      phenylsulfinyl radical (125 Da) was lost before the loss of SO(3) group (80 Da)
      or glucuronic acid (176 Da) occurred.

PMID- 18324611
TI  - Review of peripheral neuropathy in plasma cell disorders.
AB  - Peripheral neuropathy (PN) occurs frequently in patients with plasma cell
      disorders, a heterogeneous group of disorders resulting from the unregulated
      production of monoclonal proteins. This occurs both due to the dysproteinemia
      itself and as a consequence of the therapies used to treat the underlying plasma
      cell disorder. This comprehensive review of PN associated with plasma cell
      disorders will address both disease and therapy related PN, its pathogenesis and
      management with particular attention to multiple myeloma, monoclonal gammopathy
      of undetermined significance (MGUS), Waldenstrom's macroglobulinemia, POEMS
      syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy,
      and skin changes) and amyloidosis. An understanding of this topic is critical for
      health care providers treating patients with plasma cell disorders due to the
      high frequency with which it occurs, the implications it has on selecting
      therapies for the underlying disorder and to best guide management of the
      neuropathy itself.

PMID- 18324610
TI  - Investigations with O-linked protein glycosylations by matrix-assisted laser
      desorption/ionization Fourier transform ion cyclotron resonance mass
      spectrometry.
AB  - Posttranslational modifications such as glycosylation can play a fundamental role
      in signaling pathways that transform an ordinary cell into a malignant one. The
      development of a protocol to detect these changes in the preliminary stages of
      disease can lead to a sensitive and specific diagnostic for the early detection
      of malignancies such as ovarian cancer in which differential glycan patterns are
      linked to etiology and progression. Small variations in instrument parameters and
      sample preparation techniques are known to have significant influence on the
      outcome of an experiment. For an experiment to be effective and reproducible,
      these parameters must be optimized for the analyte(s) under study. We present a
      detailed examination of sample preparation and matrix-assisted laser
      desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry
      (MALDI-FT-ICR-MS) analysis of O-linked glycans globally cleaved from mucin
      glycoproteins. Experiments with stable isotope-labeled biomolecules allowed for
      the establishment of appropriate acquisition times and excitation voltages for
      MALDI-FT-ICR-MS of oligosaccharides. Quadrupole ion guide optimization studies
      with mucin glycans identified conditions for the comprehensive analysis of the
      entire mass range of O-linked carbohydrates in this glycoprotein. Separately
      optimized experimental parameters were integrated in a method that allowed for
      the effective study of O-linked glycans.

PMID- 18324612
TI  - Larvicidal activity of Kaempferia galanga rhizome phenylpropanoids towards three
      mosquito species.
AB  - BACKGROUND: This study was aimed at assessing the toxicity of ethyl cinnamate and
      ethyl p-methoxycinnamate (EMC) identified in Kaempferia galangal L.
      (Zingiberaceae) rhizome and another 12 known compounds to third-instar larvae
      from laboratory-reared Culex pipiens pallens Forskal, Aedes aegypti L. and
      Ochlerotatus togoi Theobald and field-collected C. pipiens pallens (Jinhae
      colony). Results were compared with those for fenthion and temephos. RESULTS:
      Ethyl p-methoxycinnamate was the most toxic of the test compounds to larvae of
      the three mosquito species (LC(50) 12.3-20.7 mg L(-1)) but less toxic than either
      fenthion (0.0096-0.021 mg L(-1)) or temephos (0.0039-0.0079 mg L(-1)). Ethyl
      cinnamate and 3-carene were highly active against C. pipiens pallens larvae (24.1
      and 21.6 mg L(-1)) but less toxic to A. aegypti and O. togoi larvae (ca 40 and 60
      mg L(-1) respectively). The toxicity of these compounds to larvae from the Jinhae
      colony of C. pipiens pallens was almost the same as their toxicity to the
      laboratory-reared larvae, although the larvae from the colony exhibited low
      levels of resistance to fenthion (resistance ratio 9.1) and temephos (5.8).
      CONCLUSION: Kaempferia galanga rhizome-derived materials, particularly ethyl p
      methoxycinnamate, merit further study as potential mosquito control agents for
      protection of humans and domestic animals from vector-borne diseases and nuisance
      caused by mosquitoes.

PMID- 18324613
TI  - Brand substitution or multiple switches per patient? An analysis of
      pharmaceutical brand substitution in Australia.
AB  - PURPOSE: To determine the number of times patients have brand and generic
      products substituted under Australia's Pharmaceutical Benefits Scheme (PBS) brand
      substitution policy. METHODS: A retrospective cohort study was conducted using
      Repatriation Pharmaceutical Benefits Scheme (RPBS) pharmacy claims data.
      Department of Veterans' Affairs (DVA) treatment card holders with at least two
      dispensings of atenolol, citalopram, enalapril, metformin, omeprazole or ramipril
      between 1 January 2001 and 28 February 2006 were included. Patients were followed
      from first dispensing until death, cessation or study end. The main outcome
      measure was the number of substitutions per patient during follow-up. Based on
      this, patients were defined as non-switchers, brand substitution or multiple
      switchers. RESULTS: Data for 160,145 patients were analysed. Overall more than
      80% of patients either had no switches or demonstrated brand substitution. For
      all study drugs, patients were more likely to be non-switchers than have a brand
      substitution (RR range 2.6-9.4, p < 0.0001) and were more likely to be non
      switchers than multiple switchers (RR range 3.2-35.9, p < 0.0001). Patients who
      switched were more likely to have a brand substitution than multiple switches (RR
      range 1.2-3.8, p < 0.0001). Multivariate logistic regression showed greater odds
      of being a multiple switcher with increasing number of prescribers and dispensing
      pharmacies, and increasing length of follow-up. CONCLUSIONS: Most patients in
      this study did not substitute products, and those who did were more likely to
      demonstrate brand substitution than have multiple switches. These results suggest
      that the brand substitution policy is having its intended effect for most
      patients.

PMID- 18324614
TI  - Mechanism of a gas-phase dissociation reaction of 4-aminobutyl glycosides under
      CID MS/MS conditions.
AB  - The assembly of monosaccharides during the synthetic process of glycan structures
      is responsible for the diversity of this family of molecules. Because of the
      complexity of the glycan structure, synthesis of oligosaccharides and structural
      analysis have been difficult tasks. During efforts to develop glycosides carrying
      an aglycon that can be used in both functional and structural investigations, we
      found that 4-aminobutyl glycosides fulfill these criteria. We also observed that
      the glycosidic linkage underwent an interesting dissociation reaction under
      collision-induced MS/MS, and that the reaction product is very useful in
      structural investigation based on mass spectrometry, especially since it provides
      information regarding anomeric configurations. Despite its importance, the
      reaction mechanism of the dissociation is not fully understood. For this reason,
      we studied the mechanism by synthesizing possible products and used them in
      detailed analyses based on energy-resolved mass spectrometry where the energy
      dependence of the dissociation reaction was analyzed under collision-induced
      dissociation conditions. As a result of spectral match with one of synthesized
      reference compounds, it was suggested that the dissociation reaction to generate
      a C-ion species and a pyrrolidine took place through a five-membered transition
      state in two-step reaction sequence.

PMID- 18324615
TI  - Qualitative detection of Mg content in a leaf of Hedera helix by using X-ray
      radiation from a laser plasma source.
AB  - In this article, a method to reveal the presence of Mg content inside the
      different parts of leaves of Hedera helix is presented. In fact a sample of a
      Hedera helix's leaf, commonly characterized by a green and a white side, is
      analyzed under X-ray radiation. The presence of two zones with different colors
      in the Hedera helix's leaf has not been explained. In this connection, there are
      presently three hypotheses to explain the characteristic double-color appearance
      of the leaf. The first hypothesis suggests a different cytoplasmic inheritance of
      chloroplasts at the cell division, the second a different allelic composition,
      homozygote and heterozygote, between the two zones, and finally the third the
      action of a virus which changes the color properties in the Hedera's leaves. The
      resulting effect is a different content of "something" between the green and the
      white side. We utilized X-ray radiation, obtained from a plasma source with a Mg
      target, to image Hedera helix leaves and we found that the green side of the leaf
      is highlighted. We may suppose that the reason why the X-rays from a Mg plasma
      source, allow us to pick up the green side is probably due to the greater
      presence of the amount of Mg (from chlorophyll or other complexes and/or salts)
      in the two sides, green and white, of the leaf.

PMID- 18324616
TI  - Multiple vitellogenin-derived yolk proteins in gray mullet (Mugil cephalus):
      disparate proteolytic patterns associated with ovarian follicle maturation.
AB  - Disparate proteolytic patterns of yolk proteins, derived from three types of
      vitellogenin (VgA, VgB, and VgC), were observed in gray mullet. Immuno
      biochemical analyses of extracts obtained from vitellogenic ovaries (VO) and
      ovulated eggs (OE) confirmed that a large proportion of VgA-derived lipovitellin
      (LvA) was degraded into free amino acids (FAAs) during ovarian follicle
      maturation. The maturation-associated alteration of VgB-derived Lv (LvB) involved
      only limited proteolysis; the heavy and light LvB chains were dissociated into at
      least three and one polypeptide fragments, respectively. The native mass of VgC
      derived Lv (LvC) exhibited little difference between VO and OE, although it was
      apparent that the LvC was 'nicked' during maturation, resulting in the appearance
      of several bands in OE. Similar analyses confirmed that VgA-derived beta'
      component (beta'-cA) and VgB-derived beta'-c (beta'-cB) decreased during
      maturation in both quantity and native mass, while phosvitin derived from either
      VgA (PvA) or VgB (PvB) appeared to be degraded into FAAs. The pattern of
      maturation-associated proteolysis of mullet yolk proteins is similar to that
      reported for other marine teleosts spawning pelagic eggs. However, the depository
      ratio of the three distinct types of Lv in the mullet VO appeared to be different
      from that estimated for another marine pelagophil, the barfin flounder. These
      results support a recent paradigm regarding the significance of Vg multiplicity
      upon successive physiological events in this group of fishes including the
      hydration of maturing oocytes, the acquisition of proper egg buoyancy, and the
      generation of requisite nutrient stocks for each stage of embryogenesis and
      larval development.

PMID- 18324617
TI  - Intra- and interobserver reproducibility study of early fetal growth parameters.
AB  - OBJECTIVE: To assess the intra- and interobserver reproducibility of fetal
      biometry measurements by transabdominal ultrasound in early pregnancy. METHODS:
      The study consisted of 21 singleton pregnancies with a gestational age between 9
      and 14 weeks. Intraclass correlation coefficients (ICCs) and coefficients of
      variation (CVs) were calculated. Bland and Altman plots were computed to analyze
      agreement for measurements between and among observers. Limits of agreement +/- 2
      SD for the differences in fetal biometry measurements in proportions of the mean
      of the measurements were derived. RESULTS: High intra- and interobserver ICCs
      were found, ranging from 0.998, crown-rump length (CRL) to 0.982, femur length
      (FL) and CVs ranging from 1.4% (CRL) to 5.9% (FL). Limits of agreement in the
      Bland and Altman plots ranged from - 2.7 to 2.3% (CRL) difference from the mean
      to - 13 to 23% (FL) difference. Agreement for fetal biometry increased with fetal
      size. CONCLUSIONS: This study demonstrated good reproducibility of most
      measurements of fetal biometry in early pregnancy by abdominal ultrasound. CRL
      and biparietal diameter (BPD) showed high reproducibility and agreement, and head
      circumference (HC) to a lesser extend, from 9 weeks of gestational age onwards.
      abdominal circumference (AC) is only reliable from circa 11 weeks onwards. FL has
      a poor reproducibility before 14 weeks of gestational age.

PMID- 18324618
TI  - Effect of labor on postpartum clearance of cell-free fetal DNA from the maternal
      circulation.
AB  - OBJECTIVE: The aim of this study was to compare the effect of mode of delivery on
      the postpartum clearance of cell-free fetal (cff) DNA. METHODS: Women who gave
      birth to a single-term male infant by any mode of delivery had blood collected on
      three occasions: within 3 h of birth, on day 1-2 postpartum and at 2 weeks
      postpartum. The SRY sequence was used as a marker of cff DNA, and was detected
      using conventional PCR. RESULTS: Eighty-seven women were included in the study.
      There were 28 women in the elective caesarean section group and 59 in the labor
      group. Cell-free fetal DNA was detected in 38/87 (44%) of women within 3 h of
      birth. There was a significant difference between the group that labored and the
      group that did not (54 vs 21%, p = 0.003). Twelve percent of women who labored
      had persistent cff DNA on day 1-2 postpartum, compared with none of the women who
      delivered without labor. No woman had DNA that persisted up to 2 weeks
      postpartum. CONCLUSION: The presence of labor increases the rate of detectable
      DNA in women within 3 h of birth and on day 1-2 postpartum. Postpartum clearance
      was completed by 2 weeks in all women tested regardless of mode of delivery.

PMID- 18324619
TI  - Postnatal management of prenatally diagnosed abdominal masses and anomalies.
AB  - Rapid advancement in fetal diagnostic imaging has increased our ability to
      diagnose a multitude of anomalies in the prenatal period. The purpose of this
      chapter is to review our current understanding of prenatally diagnosed intra
      abdominal lesions, and describe the current guidelines for the postnatal
      management and subsequent outcome for these lesions.

PMID- 18324620
TI  - Hepatitis C virus reinfection in liver transplant patients: evaluation of liver
      damage progression with echo-color Doppler.
AB  - Liver transplant recipients are a model of rapid progression of hepatitis C virus
      (HCV)-related liver disease, from normal to cirrhosis. The aim of the study was
      the analysis of the relationship between portohepatic hemodynamics and
      modification in liver histology during the progression of HCV liver disease after
      transplant. Patients transplanted for HCV cirrhosis were considered for the
      study. At least every 6-12 months, the portal blood flow velocity, hepatic and
      splenic pulsatility indices, and a portal hypertensive index (obtained from the
      combination of the portal blood velocity and splenic pulsatility index) were
      measured with echo-Doppler. Liver biopsy was performed whenever necessary. The
      time course of echo-Doppler parameters during the histological progression of the
      liver disease was analyzed. Posttransplant patients without HCV were included as
      controls. Forty-nine patients with histology-proven relapse of HCV hepatitis were
      included in the study. At the onset of recurrent hepatitis, the portal blood flow
      velocity significantly decreased (P < 0.001), and the splenic pulsatility index
      increased (P = 0.020), whereas the hepatic pulsatility index remained unchanged.
      In the following years, in addition to a further slight decrease in the portal
      blood velocity (P = 0.027), a progressive increase in the hepatic and splenic
      pulsatility indices was also detected (P = 0.009 and P < 0.0001, respectively).
      The portal hypertensive index steadily increased with the progression of the
      disease and was related to the degree of liver fibrosis. In conclusion, the
      information obtainable from splanchnic Doppler parameters can be used to monitor
      the progression of liver fibrosis in transplant patients with HCV reinfection.

PMID- 18324621
TI  - Should trichrome stain be used on all post-liver transplant biopsies with
      hepatitis C virus infection to estimate the fibrosis score?
AB  - Recurrent hepatitis C is virtually universal after liver transplantation;
      however, an individual patient's clinical course and disease burden are highly
      variable and difficult to predict. The fibrosis score determined on
      posttransplant biopsies appears to be a sensitive and specific marker of disease
      progression and severity. Currently, the fibrosis score is determined from
      hematoxylin and eosin (H&E)-stained tissue sections supplemented by variable use
      of trichrome stain or other connective tissue-specific stains. In this study, we
      compare the fibrosis score on H&E stain with that obtained with trichrome stain
      in posttransplant liver biopsies of patients with hepatitis C. A total of 197
      liver biopsies from 105 allograft patients with hepatitis C were reviewed. The
      mean fibrosis stage was 1.0 +/- 1.25 with H&E stain versus 1.69 +/- 1.42 with
      trichrome stain (P < 0.00001). The trichrome staging score was higher in 53.3%,
      lower in 3%, and the same in 43.7%. The fibrosis stage was raised by 2 or more
      points in 17.8% and elevated into a bridging category in 14.7%. No significant
      differences in clinical and laboratory levels were measured in patients with
      higher fibrosis scores. In conclusion, the hepatic fibrosis score is
      significantly underestimated by H&E stain in the posttransplant setting in
      patients with hepatitis C. The fibrosis stage may be an indicator of significant
      liver damage in these patients. Accuracy of its determination may be most easily
      facilitated by employment of a connective tissue stain.

PMID- 18324622
TI  - Intratesticular localization of the organic solute carrier protein, OSCP1, in
      spermatogenic cells in mice.
AB  - Organic solute carrier protein 1 (OSCP1) is a recently described human gene that
      facilitates the transport of various organic solutes into the cell, when
      expressed in frog eggs. In this study, we cloned a mouse ortholog of OSCP1
      encoding 379 amino acid protein, with 94% homology to the human counterpart. The
      mouse OSCP1 mRNA was predominantly expressed in the testis, in which it was
      attributed to the spermatogenic cells, except the spermatogonia.
      Immunohistochemistry confirmed that OSCP1 protein is continuously expressed
      during spermatogenesis in a stage- and cell type-specific manner, in the
      leptotene spermatocytes at stage IX through step 15 spermatids. Subcellular
      fractionation of mouse testis homogenates indicated that OSCP1 is a 45-kDa
      cytosolic protein. Moreover, when green fluorescent protein-OSCP1 fusion
      constructs were transfected into cultured cells, the fluorescence localized
      evenly in the cytoplasm. These results suggest that mouse testis OSCP1 may
      indirectly mediate substrate uptake into meiotic and spermiogenic germ cells,
      within the cytosol.

PMID- 18324623
TI  - A comparison of the ontogeny of shape variation in the anthropoid scapula:
      functional and phylogenetic signal.
AB  - This article compares ontogenetic shape variation in the scapula of 17 anthropoid
      species using three-dimensional landmark-based geometric morphometrics. These
      data are used to investigate functional and phylogenetic signal in the major
      components of scapular variation and to evaluate the degree to which postnatal
      growth contributes to interspecific differences in shape. Results indicate that
      the shape of the infant and adult scapula is primarily associated with positional
      behavior (e.g., orthograde suspensory nonquadrupeds versus pronograde
      quadrupeds), but within this functional structure there is phylogenetic signal,
      particularly at infant stages. Growth most closely correlates with infant/adult
      shape and locomotor function. These results suggest that the shape of the infant
      scapula drives the pattern of postnatal scapular growth and adult morphology. As
      such, variation in postnatal growth is not the primary source of interspecific
      variation in adult shape. Instead, interspecific differences in scapular
      morphology are hypothesized to be the result of selection for variation in
      embryonic developmental processes that affect shape.

PMID- 18324624
TI  - Transient ectopic expression as a method to detect genes conferring drug
      resistance.
AB  - Ectopic expression provides an alternative to RNAi to conduct functional genomic
      screens. We have determined whether transient expression can be used to identify
      genes which confer drug resistance. We constructed a bigenic vector that allows
      high throughput cloning and which also encodes a red fluorescent protein to
      monitor transfection. Assay conditions were optimized to allow detection of
      changes in sensitivity to carboplatin or paclitaxel. Following transient
      expression of MDR-1 and MCJ, changes in the sensitivity of Sk-Ov-3 cells to
      paclitaxel were detected whereas expression of Src, Bcl-2 and Bcl-X(L) decreased
      the sensitivity of Sk-Ov-3 cells to carboplatin. This approach may potentially be
      used as an independent screen or as a method to help rank hit identified in
      screens utilizing methods such as RNAi.

PMID- 18324625
TI  - Perinatal factors and the risk of testicular germ cell tumors.
AB  - Testicular germ cell tumors (TGCT) are the most common cancer among young men in
      the United States and Western Europe. Prior evidence suggests that TGCT may arise
      in perinatal life, although few risk factors have yet been identified. To study
      the etiology of TGCT, the US Servicemen's Testicular Tumor Environmental and
      Endocrine Determinants (STEED) case-control study enrolled participants and their
      mothers between 2002 and 2005. Five hundred twenty-seven mothers of cases and 561
      mothers of controls provided information on perinatal variables. Logistic
      regression was used to calculate odds ratios (OR) and 95% confidence intervals
      (95%CI) associated with the candidate risk factors. Analyses were conducted for
      all TGCT together and for each histologic subgroup (seminoma and nonseminoma)
      separately. Young maternal age (<20 vs. 20-29 years, OR = 1.51, 95%CI: 1.09
      2.10), young paternal age (<25 vs. 25-29 years, OR = 1.45, 95%CI: 1.08-1.94),
      maternal parity (3 vs. 1, OR = 0.63, 95%CI: 0.44-0.90) and breech birth (OR =
      1.92, 95%CI: 1.03-3.56) were associated with risk of TGCT. For seminoma, young
      maternal age (<20 vs. 20-29 years, OR = 1.67, 95%CI: 1.10-2.54), young paternal
      age (<25 vs. 25-29 years, OR = 1.53, 95%CI: 1.03-2.27), maternal parity (3 vs. 1,
      OR = 0.58, 95%CI: 0.35-0.96) and low birth weight (<2,500 g vs. 2,500-4,000 g, OR
      = 1.82, 95%CI: 1.00-3.30) were risk factors. Nonseminoma was associated with
      breech birth (OR = 2.44, 95%CI: 1.25-4.78) and Cesarean section (OR = 2.10,
      95%CI: 1.25-3.54). These results support the hypothesis that TGCT may originate
      in very early life.

PMID- 18324626
TI  - Saturated fat intake predicts biochemical failure after prostatectomy.
AB  - Previous reports show that obesity predicts biochemical failure after treatment
      for localized prostate cancer. Since obesity is associated with increased fat
      consumption, we investigated the role that dietary fat intake plays in modulating
      obesity-related risk of biochemical failure. We evaluated the association between
      saturated fat intake and biochemical failure among 390 men from a previously
      described prostatectomy cohort. Participants completed a food frequency
      questionnaire collecting nutrient information for the year prior to diagnosis.
      Because fat and energy intake are highly correlated, the residual method was used
      to adjust fat (total and saturated) intakes for energy. Biochemical-failure-free
      survival rates were calculated using the Kaplan-Meier method. Crude and adjusted
      effects were estimated using Cox proportional hazards models. During a mean
      follow-up of 70.6 months, 78 men experienced biochemical failure. Men who
      consumed high- saturated fat (HSF) diets were more likely to experience
      biochemical failure (p = 0.006) and had significantly shorter biochemical-failure
      free-survival than men with low saturated fat (LSF) diets (26.6 vs. 44.7 months,
      respectively, p = 0.002). After adjusting for obesity and clinical variables, HSF
      diet patients were almost twice as likely to experience biochemical failure
      (hazard ratio = 1.95, p = 0.008) compared to LSF diet patients. Men who were both
      obese and consumed HSF diets had the shortest biochemical-failure-free-survival
      (19 months), and nonobese men who consumed LSF diets had the longest biochemical
      failure-free-survival (46 months, p < 0.001). Understanding the interplay between
      modifiable factors, such as diet and obesity, and disease characteristics may
      lead to the development of behavioral and/or targeted interventions for patients
      at increased risk of progression.

PMID- 18324627
TI  - Usefulness of monitoring the circulating Krebs von den Lungen-6 levels to predict
      the clinical outcome of patients with advanced nonsmall cell lung cancer treated
      with epidermal growth factor receptor tyrosine kinase inhibitors.
AB  - Krebs von den Lungen-6 (KL-6) is a high molecular weight glycoprotein classified
      in the category of human MUC1 mucin. KL-6 has been reported to serve as a
      sensitive marker for interstitial pneumonia; however, recent studies have
      suggested that it can also be used as a tumor marker as its origin shows. To
      further elucidate the clinicopathological significance of circulating KL-6 in
      lung cancer, we monitored the circulating KL-6 levels in advanced nonsmall cell
      lung cancer (NSCLC) patients and analyzed the association between these levels
      and the clinical outcome of EGFR-TKI treatment. The pretreatment levels of
      circulating KL-6 were found to be significantly higher in progressive disease
      (PD) patients than disease-controlled (partial response (PR) and stable disease
      (SD)) patients. Multivariate analyses revealed the circulating KL-6 level to be
      an independent prognostic factor for overall survival as well as progression-free
      survival. In addition to these observations, we found that changes in circulating
      KL-6 levels at 2 weeks after the start of EGFR-TKI treatment from the baseline
      could quite precisely discriminate PD cases from PR or SD patients and the
      clinical outcome of EGFR-TKI in NSCLC patients. These results indicate that the
      monitoring of circulating KL-6 levels in NSCLC patients is effective for both
      selecting patients to be treated with EGFR-TKI and predicting the clinical
      outcome of EGFR-TKI. In addition, the findings suggest that the circulating KL-6
      level could be used as a clinically relevant biomarker in patients with NSCLC,
      particularly those who are candidates for EGFR-TKI treatment.

PMID- 18324628
TI  - Intra-operative rapid diagnostic method based on CK19 mRNA expression for the
      detection of lymph node metastases in breast cancer.
AB  - Staging by sentinel node (SN) biopsy is the standard procedure for clinically
      node-negative breast cancer patients. Intra-operative analysis of the SN allows
      immediate axillary lymph node (ALN) dissection in SN positive patients, but a
      quick, reliable and reproducible method is lacking. We tested the suitability of
      a quantitative cytokeratin 19 (CK19) mRNA one step nucleic acid amplification
      (OSNA#) technique (OSNA-CK19) for intra-operative SN analysis. OSNA-CK19 involves
      a short manual sample preparation step and subsequent fully automated
      amplification of CK19 mRNA based on reverse transcription loop-mediated
      isothermal amplification, with results available within 30-40 min. OSNA-CK19 was
      compared to histological staining (Hematoxylin&Eosin and CAM5.2 and CK19
      immunostaining) of 346 frozen ALNs from 32 breast cancer patients, using half of
      the lymph node for each method. 267 samples were negative and 61 positive by both
      methods. Three samples were histology positive and OSNA-CK19 negative. Fifteen
      samples were histology negative and OSNA-CK19 positive, 11 of which had copy
      numbers close to the cut-off level of OSNA-CK19. Seven of these 15 samples were
      RT-PCR positive for epithelial markers and/or showed CK19 protein expression by
      Western blot suggesting the presence of tumor deposits in the lymph node part
      investigated by OSNA-CK19. Concordance with histology was 94.8%, and 96.8% after
      exclusion of the latter 7 discordant cases. Sensitivity was 95.3% and specificity
      was 94.7% before and 97.1% after discordant case investigation. Our results
      indicate that OSNA-CK19 can potentially be useful in an intra-operative clinical
      setting to detect SN tumor involvement in breast cancer patients.

PMID- 18324630
TI  - Childhood cancers in Chennai, India, 1990-2001: incidence and survival.
AB  - Childhood cancers (age at diagnosis: 0-14 years) comprise a variety of
      malignancies, with incidence varying worldwide by age, sex, ethnicity and
      geography, that provide insights into cancer etiology. A total of 1,334 childhood
      cancers registered in population-based cancer registry, Chennai, India, during
      1990-2001 and categorized by International Classification of Childhood Cancer
      norms formed the study material. Cases included for survival analysis were 1,274
      (95.5%). Absolute survival was calculated by actuarial method. Cox proportional
      hazard model was used to elicit the prognostic factors for survival. The age
      standardized rates for all childhood cancers together were 127 per million boys
      and 88 per million girls. A decreasing trend in incidence rates with increasing 5
      year age groups was observed in both sexes. The top 5 childhood cancers were the
      same among boys and girls: leukemias, lymphomas, central nervous system
      neoplasms, retinoblastomas and renal tumors. The highest 5-year absolute survival
      was observed in Hodgkin's disease (65%) followed by Wilm's tumor (64%),
      retinoblastomas (48%), non-Hodgkin's lymphomas (47%), osteosarcomas (44%), acute
      lymphoid leukemia and astrocytoma (39%). Multifactorial analysis of age at
      diagnosis and sex showed no differences in the risk of dying for all childhood
      cancers. Completeness of treatment and type of hospital combination emerged as a
      prognostic factor for survival for all childhood cancers together (p < 0.001),
      acute lymphoid leukemia (p < 0.001) and non-Hodgkin's lymphoma (p = 0.04). A
      Childhood Cancer Registry with high-resolution data collection is advocated for
      in-depth analysis of variation in incidence and survival.

PMID- 18324629
TI  - Bone marrow stromal cells enhance prostate cancer cell invasion through type I
      collagen in an MMP-12 dependent manner.
AB  - At the cellular level, the process of bone metastasis involves many steps.
      Circulating cancer cells enter the marrow, proliferate, induce
      neovascularization, and ultimately expand into a clinically detectable, often
      symptomatic, metastatic deposit. Although the initial establishment and later
      expansion of the metastatic deposit in bone require tumor cells to possess
      invasive capability, the exact proteases responsible for this phenotype are not
      well known. The objective of our study was to take an unbiased approach to
      determine which proteases were expressed and functional during the initial
      interactions between prostate cancer cells and bone marrow stromal (BMS) cells.
      We found that the combination of human prostate cancer PC3 and BMS cells
      stimulates the invasive ability of cancer cells through type I collagen. The use
      of inhibitors for each of the major protease families indicated that 1 or more
      MMPs was/were responsible for the BMS-induced invasion. Gene profiling and
      semiquantitative RT-PCR analysis revealed an increased expression of several MMP
      genes because of PC3/BMS cell interaction. However, only MMP-12 showed an
      increase in protein expression. Downregulation of MMP-12 expression in PC3 cells
      by siRNA inhibited the enhanced invasion induced by PC3/BMS cell interaction. In
      vivo, MMP-12 was found to be primarily expressed by prostate cancer cells growing
      in bone. Our data suggest that BMS cells induce MMP-12 expression in prostate
      cancer cells, which results in invasive cells capable of degradation of type I
      collagen.

PMID- 18324631
TI  - Sexing skulls using discriminant function analysis of visually assessed traits.
AB  - The accuracy of sex determinations based on visual assessments of the mental
      eminence, orbital margin, glabellar area, nuchal area, and mastoid process was
      tested on a series of 304 skulls of known age and sex from people of European
      American, African American, and English ancestry as well as on an ancient Native
      American sample of 156 individuals whose sex could be reliably determined based
      on pelvic morphology. Ordinal scores of these sexually dimorphic traits were used
      to compute sex determination discriminant functions. Linear, kth-nearest
      neighbor, logistic, and quadratic discriminant analysis models were evaluated
      based on their capacity to minimize both misclassifications and sex biases in
      classification errors. Logistic regression discriminant analysis produced the
      best results: a logistic model containing all five cranial trait scores correctly
      classified 88% of the modern skulls with a negligible sex bias of 0.1%. Adding
      age at death, birth year, and population affinity to the model did not
      appreciably improve its performance. For the ancient Native American sample, the
      best logistic regression model assigned the correct pelvic sex to 78% of the
      individuals with a sex bias of only 0.2%. Similar cranial trait frequency
      distributions were found in same-sex comparisons of the modern African American,
      European American, and English samples. The sexual dimorphism of these modern
      people contrasts markedly with that of the ancient Native Americans. Because of
      such population differences, discriminant functions like those presented in this
      paper should be used with caution on populations other than those for which they
      were developed.

PMID- 18324632
TI  - Iron Age breastfeeding practices in Britain: isotopic evidence from Wetwang
      Slack, East Yorkshire.
AB  - We present here the results of carbon and nitrogen isotopic analysis of bone
      collagen undertaken on all skeletal remains of infants and young children below
      the age of 6 years (n = 34) from the internationally important British cemetery
      site at Wetwang Slack in East Yorkshire (middle Iron Age, ca. 4th to 2nd
      centuries BC). The aim of the study is to investigate infant diet, with
      particular reference to breastfeeding and weaning practices, and to compare the
      data with previously published studies of archaeological populations,
      particularly in the context of the variation in data patterns to be seen between
      sites. The skeletal remains from Wetwang Slack form the only prehistoric
      collection in the UK, prior to the Romano-British period, with sufficient
      individuals in this age group to make such an isotopic study viable alongside
      associated adults and older children. The data are compared in detail with
      published data from two other sites, one from 19th century Canada and the other
      from Medieval Britain. The results suggest an unusual situation at Wetwang Slack,
      with neither the nitrogen nor the carbon isotope ratios conforming to
      expectations when compared with the putative mothers. We discuss how these data
      compare with the expectation for breastfed infants and we interpret the
      divergence in this case to be due to restricted breastfeeding and the early
      introduction of supplementary foods.

PMID- 18324633
TI  - Growth and malnutrition of rural Zimbabwean children (6-17 years of age).
AB  - The rural environment is an important factor in delayed growth in developing
      countries. The aim of this study was to investigate the effects of poor rural
      living conditions on the growth of a Shona sample in Zimbabwe. In total, 982
      subjects aged 6-17 years were analyzed. Mean values of height, weight, skinfolds
      (triceps, subscapular, suprailiac, biceps, medial calf), cormic index, body mass
      index (BMI), arm composition (total upper arm area, upper arm muscle area, arm
      fat area, and arm fat index), fat percentage (%F), centripetal fat ratio (CFR),
      and the contribution of each skinfold to the adiposity of the trunk and upper
      limbs are presented. Weight, height, BMI, cormic index, SSCP, TRCP, arm
      circumference, and arm composition are compared with NHANES percentiles. Boys and
      girls showed stunting and underweight at ages 11-15 and 8-15, respectively; boys
      presented particularly severe malnutrition and their means of height and weight
      were below the 10th percentile. The means of arm circumference, UMA, UFA, and
      TRCP were below the 15th percentile in both sexes. The contribution of the
      skinfolds generally showed an overall prevalence of TRCP in both sexes; the
      contribution of SSCP was prevalent only for the 16- to 17-year-old boys. Males
      presented a higher CFR than girls after 14 years while females showed an
      irregular pattern. There was a high incidence of brachycormia and mesocormia in
      females and males, respectively. Height, weight, and BMI were similar to the
      values observed in other sub-Saharan countries, although body size was slightly
      larger than in South Africa and smaller than in Tanzania. The results provide a
      useful database for future comparisons.

PMID- 18324634
TI  - Brief communication: enamel thickness trends in the dental arcade of humans and
      chimpanzees.
AB  - In addition to evidence for bipedality in some fossil taxa, molar enamel
      thickness is among the few characters distinguishing (thick-enameled) hominins
      from the (thin-enameled) African apes. Despite the importance of enamel thickness
      in taxonomic discussions and a long history of scholarship, measurements of
      enamel thickness are performed almost exclusively on molars, with relatively few
      studies examining premolars and anterior teeth. This focus on molars has limited
      the scope of enamel thickness studies (i.e., there exist many fossil hominin
      incisors, canines, and premolars). Increasing the available sample of teeth from
      which to compare enamel thickness measurements from the fossil record could
      substantially increase our understanding of this aspect of dental biology, and
      perhaps facilitate greater taxonomic resolution of early hominin fossils. In this
      study, we report absolute and relative (size-scaled) enamel thickness
      measurements for the complete dentition of modern humans and chimpanzees. In
      accord with previous studies of molars, chimpanzees show lower relative enamel
      thickness at each tooth position, with little overlap between the two taxa. A
      significant trend of increasing enamel thickness from anterior to posterior teeth
      is apparent in both humans and chimpanzees, indicating that inter-taxon
      comparisons should be limited to the same tooth position in order to compare
      homologous structures. As nondestructive imaging techniques become commonplace
      (facilitating the examination of increasing numbers of fossil specimens), studies
      may maximize available samples by expanding beyond molars.

PMID- 18324635
TI  - Genetic traces of east-to-west human expansion waves in Eurasia.
AB  - In this study, we describe the landscape of human demographic expansions in
      Eurasia using a large continental Y chromosome and mitochondrial DNA dataset.
      Variation at these two uniparentally-inherited genetic systems retraces
      expansions that occurred in the past 60 ky, and shows a clear decrease of
      expansion ages from east to west Eurasia. To investigate the demographic events
      at the origin of this westward decrease of expansion ages, the estimated
      divergence ages between Eurasian populations are compared with the estimated
      expansion ages within each population. Both markers suggest that the demographic
      expansion diffused from east to west in Eurasia in a demic way, i.e., through
      migrations of individuals (and not just through diffusion of new technologies),
      highlighting the prominent role of eastern regions within Eurasia during
      Palaeolithic times.

PMID- 18324636
TI  - The range of passive arm circumduction in primates: do hominoids really have more
      mobile shoulders?
AB  - Hominoids and lorines are assumed to possess greater shoulder mobility than other
      primates. This assumption is based on morphological characteristics of the
      shoulder, rather than on empirical data. However, recent studies have shown that
      the glenohumeral joint of hominoids is not more mobile than that of other
      primates (Chan LK. 2007. Glenohumeral mobility in primates. Folia Primatol
      (Basel) 78(1):1-18), and the thoracic shape of hominoids does not necessarily
      promote shoulder mobility (Chan LK. 2007. Scapular position in primates. Folia
      Primatol (Basel) 78(1):19-35). Moreover, lorines differ significantly from
      hominoids in both these features, thus challenging the assumption that both
      hominoids and lorines have greater shoulder mobility. The present study aims to
      test this assumption by collecting empirical data on shoulder mobility in 17
      primate species. Passive arm circumduction (a combination of glenohumeral and
      pectoral girdle movement) was performed on sedated subjects (except humans), and
      the range measured on the video images of the circumduction. The motion differed
      among primate species mostly in the craniodorsal directions, the directions most
      relevant to the animal's ability to brachiate and slow climb. Hylobatids
      possessed the highest craniodorsal mobility among all primate species studied.
      However, nonhylobatid hominoids did not have greater craniodorsal mobility than
      arboreal quadrupedal monkeys, and lorines did not have greater craniodorsal
      mobility than arboreal quadrupedal prosimians. Nonhylobatid hominoids and lorines
      had similar craniodorsal mobility, but this was due to a longer clavicle, more
      dorsal scapula, and lower glenohumeral mobility in the former, and a shorter
      clavicle, less dorsal scapula, and greater glenohumeral mobility in the latter.
      This study provides evidence for the reexamination of the brachiation, slow
      climbing, and vertical climbing hypotheses.

PMID- 18324637
TI  - Dismembering bodies for display: a bioarchaeological study of trophy heads from
      the Wari site of Conchopata, Peru.
AB  - Human trophy heads from the Wari site of Conchopata (AD 600-1000) are examined to
      evaluate if recently deceased persons or old corpses were used to make trophy
      heads and determine if the modifications are standardized. Similarly styled
      trophy heads may suggest state oversight that ensured uniform modifications,
      while different styles may suggest that various factions or kin groups prepared
      them to their own specifications. Other studies often interpret trophy heads as
      either enemies or ancestors; so, this study addresses that debate by documenting
      aspects of their identity as revealed through demographic, paleopathological, and
      trauma data. Results show that "fresh" bodies, not old corpses, were used to make
      trophies, as evidenced by cutmarks indicating intentional removal of soft
      tissues. Trophy heads are remarkably standardized; 89% display a hole on the
      superior of the cranium, apparently a design feature that displays the trophy
      head upright and facing forward when suspended by a cord. Of the 31 trophy heads,
      24 are adolescents/adults and 7 are children, and of the 17 sexed adults, 15 are
      male and 2 are female. This suggests that adult men and children were favored as
      trophies. Among 19 observable adult trophy heads, 42% exhibit cranial trauma,
      suggesting that violence was common among this group. Complementary data on Wari
      iconography shows warriors wearing trophy heads and Wari deities holding captives
      and trophy heads. Thus, it is likely that captives (or just their heads) were
      taken in battles and raids-either secular or ritual-and eventually transformed
      into trophy heads.

PMID- 18324638
TI  - Delivery of noncarrier naked DNA vaccine into the skin by supersonic flow induces
      a polarized T helper type 1 immune response to cancer.
AB  - BACKGROUND: DNA vaccine is a new and powerful approach to generate immunological
      responses against infectious disease and cancer. The T helper type (Th)1 immune
      response is usually required for generating effective anti-tumor responses. A
      microparticulate bombardment system can induce an immune response using very low
      amounts of DNA. Using nozzle aerodynamics, a low pressure gene gun has been
      developed to decrease the noise associated with high pressure gene guns.
      Particles are propelled by supersonic flow through this novel nozzle. To test
      whether this gun could inoculate a DNA vaccine that stimulates an anti-tumor Th1
      immune response, we examined the effect of direct delivery of naked DNA (i.e.
      without any carrier) on the anti-tumor immune response of mice. METHODS: The
      luciferase reporter plasmid DNA was delivered using a low-pressure biolistic
      device and expressed in C3H/HeN, BALB/c, and C57BL/6 mice. RESULTS: Plasmid DNA
      expression was mainly in the epidermis. Noncarrier naked neu DNA vaccine and gold
      particle-coated neu DNA vaccine (at 1 microg per mouse) had similar anti-tumor
      effects in C3H mice. However, cytokine profile examination showed the Th1-bias of
      the response induced by naked DNA vaccine and the Th2-bias of the response
      induced by coated DNA vaccine. CONCLUSIONS: A shift in the immune response to
      favour enhanced tumor rejection can be achieved by skin delivery of naked DNA
      vaccine.

PMID- 18324639
TI  - The therapeutic potential of the proteasome in leukaemia.
AB  - Many cellular processes converge on the proteasome, and its key regulatory role
      is increasingly being recognized. Proteasome inhibition allows the manipulation
      of many cellular pathways including apoptotic and cell cycle mechanisms. The
      proteasome inhibitor bortezomib has enhanced responses in newly diagnosed
      patients with myeloma and provides a new line of therapy in relapsed and
      refractory patients. Malignant cells are more sensitive to proteasome inhibition
      than normal haematopoietic cells. Proteasome inhibition enhances many
      conventional therapies and its role in leukaemia is promising.

PMID- 18324640
TI  - In vivo real-time confocal laser scanning endomicroscopic colonoscopy for the
      detection and characterization of colorectal neoplasia.
AB  - BACKGROUND: Conventional colonoscopy has a significant false-negative rate for
      intraepithelial neoplasia. Chromoendoscopy increases sensitivity but lacks
      specificity. The aim was to assess prospectively the clinical applicability and
      predictive power of the EC3870CIFK confocal laser endomicroscope (CLE) for the in
      vivo diagnosis of intraepithelial neoplasia during colonoscopy. METHODS: Lesions
      were identified using chromoscopy followed by CLE imaging and graded according to
      vascular and cellular changes. CLE imaging of circumscribed lesions and four
      segmental 'normal' colorectal quadrants was performed. Targeted biopsy specimens
      were then compared with histopathological results. RESULTS: Forty patients
      completed the protocol (22 men and 18 women; median age 62 (range 39-82) years).
      The median duration of ileal intubation and total procedure time were 12 (range 5
      26) and 55 (range 28-92) min respectively. Chromoscopic colonoscopy revealed 162
      lesions in 39 patients. CLE imaging was obtained on all 162 lesions. Some 5422
      confocal images were compared with 802 targeted biopsy specimens. Intraepithelial
      neoplasia was predicted with an accuracy of 99.1 per cent (sensitivity 97.4 per
      cent and specificity 99.3 per cent) (P = 0.711). CONCLUSION: Confocal laser
      endomicroscopy permits high-quality cellular, subsurface vascular and stromal
      imaging, enabling prediction of intraepithelial neoplasia with a high level of
      accuracy.

PMID- 18324641
TI  - Synthesis and insecticidal activity of new 3-benzylfuran-2-yl N,N,N',N'
      tetraethyldiamidophosphate derivatives.
AB  - BACKGROUND: A series of 3-benzylfuran-2-yl N,N,N',N'-tetraethyldiamidophosphate
      derivatives were synthesized as potential new agents to control insects. Their
      structures were confirmed on the basis of IR, NMR and MS analyses. RESULTS: Ten 3
      benzylfuran-2-ylN,N,N',N'-tetraethyl derivatives were prepared from the compound
      furan-2-yl N' (N,N,N',N'-tetraethyldiamidophosphate). The contact toxicity of all
      derivatives, at a dose of 10 microg mg(-1) insect, was evaluated against four
      insect species, Ascia monuste orseis Latr. (Lepidoptera: Pyralidae), Diaphania
      hyalinata (L.) (Lepidoptera: Pyralidae), Sitophilus zeamais Mots. (Coleoptera:
      Bruchidae) and Solenopsis saevissima (Smith) (Hymenoptera: Formicidae). The
      mortality range observed for some derivatives, such as 3-(3-methylbenzyl)furan-2
      yl N,N,N',N'-tetraethyldiamidophosphate (82.5% mortality against D. hyalinata;
      100% mortality against S. saevissima), was comparable with that of the commercial
      insecticide chlorpyrifos-methyl. The biological activity of the derivatives
      depended on the substitution pattern of the benzylic ring. Furan-2-yl N,N,N',N'
      tetraethyldiamidophosphate, furan-2-yl N,N-diethylamidochlorophosphate and
      difuran-2-yl N,N-diethylamidophosphate were also evaluated, displaying, in some
      cases, activity comparable with that of chlorpyrifos-methyl (90%, 100% and 97.5%
      respectively against A. monuste orseis). Considerable activity was observed for
      some furan-2(5H)-ones evaluated. CONCLUSION: Ten 3-benzylfuran-2-yl N,N,N',N'
      tetraethyldiamidophosphate derivatives were synthesized and fully characterized
      from a chemical point of view. The results obtained from the biological assays
      indicate that this class of compounds can be utilized for the design of new
      substances endowed with insecticidal activity.

PMID- 18324642
TI  - Anthropometric changes in children and adolescents from 1965 to 2005 in Korea.
AB  - The aim of this study was to assess the secular growth changes in Korean children
      and adolescents during the last four decades. In 2005, 68,790 boys and 62,557
      girls were recruited for this study across the nation in 2005. Anthropometric
      data (weight, height, etc.) were measured. We compared the results of previous
      nationwide growth studies with this study. The results of this survey indicate
      that the growth and developmental status of Korean children and adolescents has
      been changed substantially compared with those in 1965, 1975, 1984, and 1997. The
      data presented in this study show a distinct secular increase in growth in body
      height and weight of Korean children and adolescents spanning this period. A
      nationwide survey every 5 years would be beneficial to establish a reference
      standard for the growth of children and adolescents according to the
      socioeconomic, environmental, and nutritional changes.

PMID- 18324643
TI  - Biomechanical implications of degenerative joint disease in the apophyseal joints
      of human thoracic and lumbar vertebrae.
AB  - An experimental technique for quantifying load-sharing in cadaveric spines is
      used to test the hypothesis that degenerative changes in human apophyseal joints
      are directly related to high levels of compressive load-bearing by these joints.
      About 36 cadaveric thoraco-lumbar motion segments aged 64-92 years were subjected
      to a compressive load of 1.5 kN. The distribution of compressive stress was
      measured in the intervertebral discs using a miniature pressure transducer, and
      stress measurements were summed over area to give the compressive force resisted
      by the disc. This was subtracted from the applied 1.5 kN to indicate compressive
      load-bearing by the apophyseal joints. The cartilage of each apophyseal joint
      surface was then graded for degree of degeneration. After maceration, each joint
      surface was scored for degenerative joint disease (DJD) affecting the bone.
      Results demonstrated that the apophyseal joints resisted 5-96% (mean 45%) of the
      applied compressive force. A significant positive correlation was demonstrated
      between age and cartilage degeneration, age and DJD bone score, apophyseal joint
      load-bearing and bone score, and cartilage score and load-bearing. The latter
      correlation was strongest for load-bearing above 50%. Ordinal regression showed
      that the variables describing bone DJD (marginal osteophytes, pitting, bony
      contour change, and eburnation) were significantly correlated with degree of
      cartilage degeneration. It is concluded that in elderly individuals apophyseal
      joint load-bearing above a threshold of 50% is associated with severe
      degenerative changes in cartilage and bone, and that markers of DJD observed
      palaeopathologically may be used as predictors of such loadingin life.

PMID- 18324644
TI  - Brief communication: physiological stress in the Florida Archaic-enamel
      hypoplasia and patterns of developmental insult in early North American hunter
      gatherers.
AB  - We examined the prevalence and developmental timing of linear enamel hypoplasias
      (LEHs) in an early Archaic Floridian population from Windover (8,120-6,980 (14)C
      years B.P. uncorrected). Using digital images, mandibular and maxillary canines
      were analyzed for defect prevalence and timing of insults. Although overall
      prevalence was very weakly correlated with earlier defect timing, there were
      significant differences in defect prevalence that varied by sex and tooth type.
      The mean LEH count in male mandibular canines was far higher than in male
      maxillary canines or in female mandibular or maxillary canines. We examined
      defect timing as a possible predictor of the sex differences in LEH prevalence.
      There were no significant sex differences in the developmental timing of the
      earliest defects in either tooth class. Developmental timing is not responsible
      for the sex differences seen in defect prevalence in mandibular canines.

PMID- 18324645
TI  - Chronic azacitidine treatment results in differentiating effects, sensitizes
      against bicalutamide in androgen-independent prostate cancer cells.
AB  - BACKGROUND: About 20-30% of hormone-independent PCa are characterized by the
      extensive loss of AR expression that appears to occur at the transcriptional
      level. Treatment of AR-negative PCa cells with demethylating agents (Aza-CR)
      leads to expression of AR mRNA and protein. Here, we investigate the effect of
      Aza-CR administered both acutely and chronically on AR expression, PSA
      expression, cell survival, and proliferation in androgen-independent/AR-negative
      PCa cells. We also studied whether epigenetically reactivated AR is a target for
      bicalutamide therapy. METHODS: The in vitro effect of Aza-CR as single agent and
      its ability to induce AR expression and to augment the efficacy to bicalutamide
      were assessed using two androgen-independent and AR-negative cell lines (PC3 and
      DU145). RESULTS: Our results show that acute treatment (4 days) with Aza-CR
      results in a relatively low decrease in cell proliferation with G2 cell cycle
      arrest and no significant evidence of apoptosis or AR expression. Interestingly,
      when Aza-CR was chronically administered (20 days), this treatment resulted in
      marked decrease in tumor cell proliferation with significant increase in AR and
      PSA protein levels. Furthermore, following Aza-CR chronic treatment the formerly
      androgen-independent PC3 and DU145 cells increase their susceptibility to the
      apoptotic effects of bicalutamide. CONCLUSIONS: Aza-CR acute treatment has modest
      effects on androgen-independent and AR-negative PCa cell survival and
      proliferation, but chronic administration results in profound decrease in
      proliferation and in sensitization to antiandrogen agents. All these effects
      seem, in some measure, dependent on a partial restoration of androgen regulation.

PMID- 18324646
TI  - Experimental therapy of prostate cancer with novel natural product anti-cancer
      ginsenosides.
AB  - BACKGROUND: Ginseng and its components exert various biological effects,
      including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor
      activity, and recent research has focused on their value in human cancer
      prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH
      PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated
      their anti-cancer activity in vitro. METHODS: We compared the effects of the two
      compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse
      PC3 xenograft tumor model. We also accomplished a preliminary determination of
      the mechanisms of action of the compounds. RESULTS: 25-OH-PPD, but not 25-OH-PPT,
      inhibited prostate cancer cell growth and proliferation, induced apoptosis, and
      led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3
      xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and
      could be safely combined with chemotherapeutic agents (taxotere and gemcitabine)
      and radiation therapy to improve the anti-tumor effects. Further, in both PC3 and
      LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced
      PARP cleavage and activated caspases. The compound also reduced expression of
      MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle
      arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated
      low toxicity to non-cancer cells and no observable host toxicity in animals
      either alone or in combination with conventional therapies. CONCLUSIONS: The
      newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate
      cancer therapeutic agent.

PMID- 18324647
TI  - In vivo and in vitro studies of anticancer actions of alpha-TEA for human
      prostate cancer cells.
AB  - BACKGROUND: Vitamin E analog, 2,5,7,8-tetramethyl-2R-(4R,8R, 12
      trimethyltridecyl) chroman-6-yloxyacetic acid, referred to as alpha-TEA induces
      apoptosis in a variety of human cancer cells in cell culture and reduces tumor
      burden and metastases in preclinical animal models of breast and ovarian cancer.
      The goal of this study was to determine in vivo anticancer efficacy of alpha-TEA
      against human prostate cancer cells and identify mechanisms of action. METHODS: A
      PC-3-GFP xenograft model was used to assess the effects of alpha-TEA formulated
      in liposomes and administered orally on tumor burden and metastases. Tumor tissue
      was examined by immunohistochemical staining for percentage of cells undergoing
      apoptosis by TUNEL or cell proliferation by Ki-67. In vitro analyses of
      mechanisms employed western immunoblotting to examine effects of alpha-TEA
      treatments in LNCaP and PC-3-GFP cells on levels of pro-survival and pro-death
      factors. Functional significance was determined using ectopically expressed
      constitutively active forms, inhibitors, or siRNA. RESULTS: alpha-TEA
      significantly reduced tumor burden and metastases, increased apoptosis and
      decreased proliferation of tumor cells (P < 0.05). alpha-TEA treatment of both
      LNCaP and PC-3-GFP cells in vitro reduced levels of pAkt1, pAkt2; FOXO1, c
      FLIP(L) and survivin. Constitutively active Akt1, Akt2, c-FLIP or survivin
      reduced alpha-TEA-induced apoptosis. PI3K inhibitor enhanced apoptosis.
      Constitutively active FOXO1 enhanced alpha-TEA induced Fas ligand expression;
      whereas, FOXO1 siRNA reduced alpha-TEA induced Fas ligand expression.
      CONCLUSIONS: alpha-TEA is an effective anticancer agent for human prostate cancer
      cells. Downregulation of pro-survival and upregulation of pro-death factors play
      roles in alpha-TEA-induced apoptosis.

PMID- 18324648
TI  - Elevated levels of HER-2/neu and androgen receptor in clinically localized
      prostate cancer identifies metastatic potential.
AB  - BACKGROUND: In this study, we investigated the expression of HER-2/neu and AR in
      clinically organ-confined prostate cancer to determine whether alterations in
      these signaling pathways contribute to the development of metastatic disease.
      METHODS: HER-2/neu and AR immunoreactivity were evaluated in archived prostatic
      tissues obtained from 53 men with clinically organ-confined disease who underwent
      radical prostatectomy. Associations between AR and HER-2/neu immunostaining and
      disease outcome were determined. RESULTS: Seventy percent (37/53) of tumors
      exhibited high levels of HER-2/neu immunostaining and 68% (36/53) of tumors had
      elevated AR levels. Patients with high levels of both HER-2/neu and AR had the
      highest rate of PSA failure (56%, 15/27) compared with no PSA failures amongst
      seven patients with low levels of both HER-2/neu and AR (log rank statistic 7.69,
      P = 0.021). Concurrent high levels of HER-2/neu and AR expression were
      significantly associated with high pathological stage (P = 0.027) and development
      of metastatic disease (P = 0.022). CONCLUSIONS: These findings support the notion
      that both the HER-2/neu and AR signaling pathways may contribute to development
      of metastatic disease. The subset of prostate tumors with increased HER-2/neu and
      AR levels may benefit from treatment strategies that target both signaling
      pathways.

PMID- 18324649
TI  - Low-level defective processing of non-verbal sounds in dyslexic children.
AB  - We compared processing of non-verbal auditory stimuli by dyslexic and non
      dyslexic children using electrophysiological methods. The study included 39
      children (17 with dyslexia plus 22 controls) assessed via frontal, central,
      parietal, and temporal electrodes. As an extension of previous P300 event-related
      potential studies, we analysed variations in the power values of 40-Hz
      oscillations (gamma-band oscillations involved in cognitive processing) during a
      specific time window in response to the auditory 'oddball' paradigm that entail
      target (random 2 kHz) and standard (frequent 1 kHz) stimuli. Dyslexic children
      differed significantly from controls (P<0.001) in the mean power of the wavelet
      transformed 40-Hz oscillation in a time interval starting at 25 ms after stimulus
      onset up to 50 ms. This means defective processing of sounds. Within groups,
      standard and target tones elicited significantly different power values
      (P<0.001). Correlations of values between standard and target responses at each
      electrode position were not significant within either group, although dyslexics
      showed a lower correlation than controls. Significant differences in the mean
      power of these oscillations detected at very early stages of auditory processing
      in dyslexic children and the wide range of mean values reveal impairment in
      processing non-verbal sounds in dyslexia. Our results also support recent
      findings using behavioural and electrophysiological methods suggesting that
      dyslexia is a general auditory deficit instead of a speech-specific deficit.

PMID- 18324650
TI  - Pyridine-N-oxide as a mild reoxidant which transforms osmium-catalyzed oxidative
      cyclization.

PMID- 18324651
TI  - Direct and waste-free amidations and cycloadditions by organocatalytic activation
      of carboxylic acids at room temperature.

PMID- 18324652
TI  - Direct visualization of oxygen distribution in operating fuel cells.

PMID- 18324653
TI  - [Mn6] under pressure: a combined crystallographic and magnetic study.

PMID- 18324654
TI  - Chiral Bronsted acid catalyzed asymmetric Baeyer-Villiger reaction of 3
      substituted cyclobutanones by using aqueous H2O2.

PMID- 18324655
TI  - Direct formation of element chlorides from the corresponding element oxides
      through microwave-assisted carbohydrochlorination reactions.
AB  - A series of technically and economically important element chlorides-such as
      SiCl4, BCl3, AlCl3, FeCl2, PCl3 and TiCl4-was synthesized through reactions
      between hydrogen chloride and the corresponding element oxides in the presence of
      different carbon sources with microwave assistance. This process route was
      optimized for demonstration purposes for tetrachlorosilane formation and
      successfully demonstrates the broad applicability of various silicon oxide
      containing minerals and materials for carbohydrochlorination. The chlorination
      reaction occurs at lower temperatures than with conventional heating in a tubular
      oven, with substantially shorter reaction times and in better yields:
      quantitatively in the case of tetrachlorosilane, based on the silicon content of
      the starting material. The experimental procedure is very simple and provides
      basic information about the suitability of element compounds, especially element
      oxides, for carbohydrochlorination. According to the general reaction sequence
      element oxide-->element-->element chloride used in today's technology, this one
      step carbohydrochlorination with hydrogen chloride is considerably more
      efficient, particularly in terms of energy input and reaction times, avoiding the
      isolation of the pure elements required for chlorination to give the element
      chlorides with use of the more corrosive and toxic chlorine gas.

PMID- 18324656
TI  - Sirolimus-based immunosuppression following liver transplantation for
      hepatocellular carcinoma.
AB  - Experience with sirolimus (SRL)-based immunosuppression following orthotopic
      liver transplantation (OLT) is rapidly accumulating. In combination with
      calcineurin inhibitors (CNIs), SRL may reduce the incidence of acute rejection
      and lower overall required drug levels. This study sought to quantify long-term
      outcome following OLT in patients with cirrhosis and concomitant hepatocellular
      carcinoma (HCC) who were treated with an SRL-based regimen as a primary therapy.
      From January 2000 to June 2007, 97 patients underwent OLT for end-stage liver
      disease and HCC at the University of Colorado Health Sciences Center. Of those,
      45 patients received SRL, in addition to CNIs, as a component of their primary
      immunosuppression regimen post-OLT. Conversely, 52 patients received the standard
      immunosuppression regimen including CNIs, mycophenolate mofetil, and
      corticosteroids. The 2 treatment groups were compared with respect to the
      following variables: age, gender, tumor stage by explant, grade, size, presence
      of vascular invasion, focality, Child's class, baseline creatinine, and warm and
      cold ischemic times. The 2 groups were comparable by all factors save for cold
      ischemic time, which was significantly longer in the CNI-treated group. Overall
      survival at 1 and 5 years post-OLT for patients treated with SRL was 95.5% and
      78.8%, respectively. Conversely, survival in patients treated with CNIs
      exclusively at the same time intervals was 83% and 62%. Although there was no
      difference in the incidence of major complications, the SRL group experienced a
      modest improvement in renal function. Cumulatively, these data suggest a
      potential survival benefit with SRL-based therapy in patients undergoing OLT for
      end-stage liver disease and concomitant malignancy.

PMID- 18324657
TI  - Utility of liver allograft biopsy obtained at procurement.
AB  - Extended-donor criteria (EDC) liver allografts potentiate the role of procurement
      biopsy in organ utilization. To expedite allocation, histologic evaluation is
      routinely performed upon frozen-section (FS) specimens by local pathologists.
      This descriptive study compares FS reports by local pathologists with permanent
      section (PS) evaluation by dedicated hepatopathologists, identifies histologic
      characteristics underrepresented by FS evaluation, and evaluates the efficacy of
      a biopsy decision analysis based on organ visualization. Fifty-two liver
      transplants using EDC allografts evaluated by FS with PS were studied. Pathologic
      worksheets created by an organ procurement organization were applied in 34 FS. PS
      analysis included 7 staining procedures for 8 histologic criteria. PS from 56
      additional allografts determined not to require donor biopsy were also analyzed.
      A high correlation was observed between FS and PS. Underestimation of steatosis
      by FS was associated with allograft dysfunction. Surgical assessment of
      cholestasis, congestion, and steatosis was accurate whereas inflammation,
      necrosis, and fibrosis were underestimated in allografts suffering parenchymal
      injury. In conclusion, the correlation between FS and PS is high, and significant
      discrepancies are rare. Biopsy is not a prerequisite for EDC utilization but is
      suggested in hepatitis C, hypernatremia, donation after cardiac death, or
      multiple EDC indications. Implementation of a universal FS worksheet could
      standardize histologic reporting and facilitate data collection, allocation, and
      research.

PMID- 18324658
TI  - Endogenous A1 adenosine receptors protect against hepatic ischemia reperfusion
      injury in mice.
AB  - Hepatic ischemia reperfusion (IR) injury is a major clinical problem during the
      perioperative period and occurs frequently after major hepatic resection or liver
      transplantation. Exogenous and endogenous A(1) adenosine receptor (A(1)AR)
      activation protects against renal IR injury. In this study, we questioned whether
      exogenous and endogenous A(1)AR activation protects against hepatic IR injury in
      vivo. A(1)AR wild-type (WT) or knockout mice were subjected to 60 minutes of
      partial hepatic IR. Some animals were treated with a selective A(1)AR agonist, 2
      chloro-N(6)-cyclopentyladenosine (CCPA; 0.1 mg/kg), or a selective A(1)AR
      antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.4 mg/kg), 15 minutes
      before hepatic ischemia. Twenty-four hours after hepatic IR, the A(1) knockout
      mice and DPCPX-treated A(1) wild-type (A(1)WT) mice developed significantly worse
      liver injury (alanine aminotransferase, liver necrosis, neutrophil infiltration,
      and apoptosis) compared to A(1)AR WT mice. However, the selective A(1)AR agonist
      CCPA failed to protect against hepatic IR injury in A(1)WT mice. Our results show
      that the endogenous A(1)ARs protect against hepatic IR injury in vivo by
      primarily reducing apoptosis and necrosis with subsequent reductions in
      proinflammatory neutrophil infiltration. However, in contrast to the kidneys, in
      which exogenous A(1)AR activation protected against IR injury, exogenous A(1)AR
      activation failed to protect against liver injury after IR. We conclude that
      endogenous A(1)AR activation prevents worsened murine liver IR injury primarily
      by reducing necrotic and apoptotic cell death. Harnessing the mechanisms of
      cytoprotection with endogenous A(1)AR activation may lead to new therapies for
      perioperative hepatic IR injury.

PMID- 18324659
TI  - COMT polymorphisms affecting protein expression are risk factors for endometrial
      cancer.
AB  - In estrogen metabolic pathways, the COMT enzyme is related to detoxification.
      COMT gene polymorphisms have been shown to effect enzyme function. We
      hypothesized that these polymorphisms may be risk factors for endometrial cancer
      (EC). DNA samples from 150 cases of EC and healthy controls (n = 165) were
      analyzed by PCR-RFLP to determine the genotypic frequency of four different
      polymorphic loci on COMT [codon 62 (rs4633), 102 (rs5031015), 136 (rs4818), 158
      (rs4680)]. Genotyping was confirmed by direct DNA sequencing. We also conducted
      haplotype analysis of COMT and investigated the relationship between COMT
      expression and COMT SNPs in EC tissues by immunohistochemistry. A significant
      increase in the T/T genotype of codon 62 (C/T) was observed in patients compared
      to controls (OR = 2.39, 95% CI: 1.31-4.37, P = 0.004). The frequency of the C-G
      haplotype of codon 62 C/T and codon 158 G/A was significantly higher in controls
      (P < 0.0001) than in patients. The expression level of COMT protein in EC tissues
      was significantly lower in COMT codon 62 variant TT and codon 158 variant AA
      genotype carriers. Therefore, the EC samples with polymorphic variants of COMT
      lead to lower expression of COMT protein whereas EC samples with wild-type codon
      62 C/C and codon 158 G/G have higher expression of COMT protein. This is the
      first study demonstrating that polymorphisms in COMT codon 62 and codon 158
      altered protein expression levels in EC, suggesting that they may be risk factors
      for EC in Caucasians.

PMID- 18324660
TI  - Gene expression profiling as a tool for basic analysis and clinical application
      of human cancer.
AB  - The sequentiation of the human genome, together with the development of high
      throughput technologies, particularly gene-expression profiling, is giving us the
      opportunity to describe biological features in a quantitative manner. Here we
      review the use of global gene expression analyses in cancer research. Microarray
      analyses of tumor samples have allowed researchers the development of profiles
      that can distinguish, identify and classify discrete subsets of disease, predict
      the disease outcome, or the response to therapy. Profiling of experimental models
      with activation of certain oncogenic pathways could also be used to ascertain the
      molecular events involved in the establishment and development of tumors and,
      consequently, these models could be validated as tools for preclinical therapy.
      Furthermore, the detailed analysis of gene expression deregulation after response
      to the therapies in such models would allow us to predict the response to
      specific drugs, and to target the therapies to patients in search for
      individualized management of the disease.

PMID- 18324661
TI  - Exposures in painting related occupations and risk of selected cancers: results
      from a case-control study in Montreal.
AB  - BACKGROUND: Painters are considered to be at increased risk of lung cancer. The
      objective was to evaluate risk of several cancers, apart from lung, in painting
      related professions. Most previous studies have focused on the job title rather
      than on exposures incurred. METHODS: A large population based case-control study
      was carried out during 1979-1986 in Montreal including several types of cancer
      and focusing on occupational exposures. Interviews elicited detailed lifetime job
      histories; those were evaluated by a team of industrial hygienists to assign
      exposure. The exposure checklist included three paint-related substances: metal
      coatings, wood varnishes and stains, and wood and gypsum paints. Seven types of
      cancer were analyzed (numbers interviewed): esophagus (97), stomach (248),
      colorectal (754), prostate (438), bladder (478), kidney (174) and non-Hodgkin's
      lymphoma (215). For each cancer type, a pooled control group was constituted from
      533 population controls and 533 cancer patients selected from other types of
      cancer. Odds ratios (ORs) were estimated between each of the paint-related agents
      and each of the seven cancer types, adjusting for several potential confounders,
      including smoking. RESULTS: The job title of "painters" was not associated with
      risk of any of the cancers under study. Most of the ORs between the three agents
      and the seven cancers were close to null. However, there was a tendency for ORs
      to be above 1.0 for subjects who had substantial exposure to metal coatings, with
      noteworthy associations for cancers of the esophagus (OR = 4.2; 95% CI: 1.1-17.0;
      n = 4), prostate (OR = 2.7; 95% CI: 1.0-7.7; n = 13), and bladder (OR = 1.7; 95%
      CI: 0.7-4.4; n = 13). CONCLUSION: These results are compatible with an absence of
      risk among painting-related professions; they are also compatible with excess
      risk of certain cancers, especially among those exposed to metal coatings.

PMID- 18324662
TI  - Early childhood temperament in pediatric bipolar disorder and attention deficit
      hyperactivity disorder.
AB  - Recent theories suggest that children with pediatric bipolar disorder (PBD) may
      exhibit more difficult temperaments premorbidly, including traits such as
      behavioral disinhibition and difficulty with emotion regulation. We investigated
      temperament characteristics retrospectively during infancy and toddlerhood in
      subjects with PBD (n=25), attention-deficit/hyperactivity disorder (ADHD; n=25),
      and healthy controls (n=25). Children with PBD were reported to experience
      increased difficult temperament in both infancy and toddlerhood compared to
      children with ADHD. Several characteristics of difficult temperament were
      associated with residual symptoms of mania and depression. Difficult premorbid
      temperament characteristics may be a specific indicator of a bipolar diathesis,
      or might signal underlying dysfunction in affective processes that significantly
      increase risk for a mood disorder.

PMID- 18324663
TI  - Bipolar disorders across the lifespan. Preface.

PMID- 18324664
TI  - Hypomanic symptoms among first-time suicide attempters predict future multiple
      attempt status.
AB  - Past conceptual and empirical works have identified unique differences between
      multiple suicide attempters, single attempters, and zero attempters, but have
      overlooked two distinct subgroups of single attempters: true single attempters
      who will not attempt suicide again, and future multiple attempters who will.
      Consistent with fluid vulnerability theory, the authors hypothesized that
      subgroups should have differences in personality traits that can predict if a
      first-time attempter is likely to attempt suicide again. In a sample of 127
      military members (81% male, 19% female) participating in a clinical intervention
      study for suicidal behaviors, hypomanic symptoms -- not personality traits --
      predicted future multiple attempters, and future multiple attempters more
      frequently met criteria for a bipolar-spectrum disorder. Clinical implications
      and convergence of findings with fluid vulnerability theory and existing research
      are discussed.

PMID- 18324665
TI  - Restructuring mood in cyclothymia using cognitive behavior therapy: an intensive
      time-sampling study.
AB  - Hypotheses predicting how cognitive behavioral therapy (CBT) would change the
      daily pattern of mood and sleep in a patient with cyclothymia were formulated
      based on circadian processes. Using a prospective single-case experimental
      design, the patient provided mood ratings every 4 hours and sleep reports daily
      for 49 weeks, including a 4-week baseline, a 20-session CBT intervention, and a
      follow-up period. Improvements in mood during and after therapy were accounted
      for by reduced daily mood variability and extended sleep. The patient's energy at
      different times of day was explained by adjusting the endogenous rhythm in a
      mathematical circadian model. Treatment of cyclothymia and related bipolar
      disorders may be enhanced by integrating understanding of circadian mood
      regulation into CBT treatment.

PMID- 18324666
TI  - Sustained and focused hepatitis B virus nucleocapsid-specific T-cell immunity in
      liver transplant recipients compared to individuals with chronic and self-limited
      hepatitis B virus infection.
AB  - Hepatitis B virus (HBV) recurrence after orthotopic liver transplantation (OLT)
      is associated with poor graft- and patient-survival. Treatment with HBV-specific
      immunoglobulins (HBIG) in combination with nucleos(t)ide analogs is effective in
      preventing HBV reinfection of the graft and improving OLT outcome. However, the
      role of HBV-specific cellular immunity in viral containment in immune suppressed
      patients in general and in OLT recipients in particular is unclear. To test
      whether or not OLT recipients maintain robust HBV-specific cellular immunity, the
      cellular immune response against HBV was assessed in 15 OLT recipients and 27
      individuals with chronic and 24 subjects with self-limited HBV infection,
      respectively; using an overlapping peptide set spanning the viral nucleocapsid-
      and envelope-protein sequences. The data demonstrate that OLT recipients mounted
      fewer but stronger clusters of differentiation (CD)8 T cell responses than
      subjects with self-limited HBV infection and showed a preferential targeting of
      the nucleocapsid antigen. This focused response pattern was similar to responses
      seen in chronically infected subjects with undetectable viremia, but
      significantly different from patients who presented with elevated HBV viremia and
      who mounted mainly immune responses against the envelope protein. In conclusion,
      virus-specific CD4 T cell-mediated responses were only detected in subjects with
      self-limited HBV infection. Thus, the profile of the cellular immunity against
      HBV was in immune suppressed patients similar to subjects with chronic HBV
      infection with suppressed HBV-DNA.

PMID- 18324667
TI  - Predictors of the duration of exclusive breastfeeding among first-time mothers.
AB  - Few women currently meet revised WHO recommendations to breastfeed exclusively
      for 6 months postpartum. In this prospective study we aimed to determine the
      influence of socio-demographic, psychosocial, and perinatal factors on the length
      of exclusive breastfeeding among 189 Canadian primiparous mothers. A majority of
      the participants did not meet their exclusive breastfeeding goals, and only 5%
      breastfed exclusively for a full 6 months. Breastfeeding self-efficacy, in
      hospital formula supplementation, prenatal class attendance, and type of delivery
      independently predicted exclusive breastfeeding duration. Findings underscore the
      complex interplay of factors influencing breastfeeding, highlight the early
      postpartum weeks as a critical period for the establishment of exclusive
      breastfeeding, and suggest the need for a continuum of pre- and postnatal
      strategies for prolonging the exclusive breastfeeding period.

PMID- 18324668
TI  - Involvement of mitogen-activated protein kinase (MAPK) pathway in LH- and meiosis
      activating sterol (MAS)-induced maturation in rat and mouse oocytes.
AB  - Gonadotropic stimulation of meiotic resumption in mice is dependent upon mitogen
      activated protein kinase (MAPK) activation in the somatic compartment of the
      follicle. By contrast, spontaneous resumption of meiosis is independent of MAPK
      activation. In view of the suggested role of meiosis-activating sterol (MAS) in
      oocyte maturation we have (i) compared MAPK activation in rat preovulatory
      follicles stimulated by LH or by accumulation of endogenous MAS by using an
      inhibitor of MAS conversion, AY9944; (ii) examined whether stimulation of meiosis
      by MAS is dependent upon MAPK activation using denuded oocytes (DO) of Mos- null
      mice (hereafter Mos(-/-)) with oocytes unable to activate MAPK. Rat preovulatory
      follicles responded to LH or AY9944 stimulation by MAPK activation. Inhibition of
      MAPK phosphorylation blocked both LH- and AY9944 triggered resumption of meiosis.
      In mouse cumulus-enclosed oocytes (CEOs) and DOs AY9944 stimulated GVB in wild
      type and Mos(-/-) mouse CEOs cultured with hypoxanthine (Hx). Addition of MAS or
      AY9944 to mouse DOs cultured with Hx induced resumption of meiosis only in wild
      type and Mos(+/-) oocytes, but they were ineffective in Mos(-/-) oocytes. The
      observed sluggish activation of MAPK induced by AY9944 in rat follicle-enclosed
      oocytes (FEO) may cause the delay in meiotic resumption in response to MAS and
      AY9944 stimulation. Further, it is incompatible with the suggested role of MAS as
      an obligatory mediator of LH in the induction of meiotic maturation. MAPK/MOS
      activation, whether in the somatic compartment or in denuded oocytes, is required
      for MAS- like LH-, FSH-, or EGF-induced resumption of meiosis.

PMID- 18324669
TI  - Developmental potential of selectively enucleated immature mouse oocytes upon
      nuclear transfer.
AB  - Selective enucleation (SE) was applied to germinal vesicle (GV) oocytes by
      removing the chromatin attached to nuclear envelope, and leaving the liquid
      contents of GV in the cytoplast. However, after reconstruction with 1/8
      blastomeres or fetal fibroblasts (FFs) neither the maturation efficiency nor the
      frequency of normal (asymmetric) division was improved as compared with
      completely enucleated (CE) oocytes. Chromosomal aberrations introduced with
      somatic nuclei were not rescued in SE oocytes either. On the other hand, timing
      of maturation division in SE GV oocytes, but not in CE GV oocytes, reconstructed
      with GV-karyoplasts was like in the control. After maturation and fertilization
      in vitro, SE oocytes reconstructed with 1/8 blastomeres developed nucleolated
      donor pronuclei, contrary to CE oocytes. The latter could be rescued with
      nucleoli-containing nucleus, but not anucleolate nucleus, from a 1/2 blastomere.
      SE oocytes reconstructed with FFs contained nucleolated pronuclei upon
      activation, unlike CE GV oocytes. These experiments show that the ooplast
      nucleolar material and/or embryonic nucleolus are indispensable for pronuclei
      formation. SE oocytes reconstructed with 1/8 blastomeres or FFs failed to cleave
      after activation or in vitro fertilization. Control GV oocytes enucleolated
      before fertilization seized cleavage at the 6-cell stage, as oppose to intact GV
      oocytes, which in 50.9% yielded morulae/blastocysts. These results suggest that
      ooplast nucleolar material is essential for the cleavage divisions. Activation of
      cumulus-enclosed SE GV oocytes matured in hormone-supplemented medium and fused
      to 1/2 blastomere-karyoplasts, yielded morulae, and blastocysts in 45.5% and
      23.4% of reconstructed oocytes, respectively.

PMID- 18324670
TI  - Effect of prostaglandin E2 and tumor necrosis factor alpha on the VEGF-receptor
      system expression in cultured porcine luteal cells.
AB  - The purpose of the present study was to investigate the effects of prostaglandin
      (PG) E(2) and tumor necrosis factor (TNF) alpha on expression of vascular
      endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase (Flt
      1) and fetal liver kinase-1/kinase insert domain-containing receptor (Flk-1/KDR),
      in cultured porcine luteal cells. Real-time PCR was used for quantification of
      VEGF and its receptors mRNA, whereas VEGF release by luteal cells was determined
      by radioimmunoassay (RIA). Only the highest dose of PGE(2) (1 microM) after 6 hr
      of incubation stimulated VEGF release by luteal cells collected in the mid-luteal
      phase (P < 0.05). Moreover, PGE(2) (100 nM, 1 microM) significantly stimulated
      VEGF secretion by luteal cells in the late phase and during pregnancy on Days 10
      12 (P < 0.05). Elevated mRNA expression of both VEGF 120 and VEGF 164 isoforms
      was found in luteal cells cultured with PGE(2). The lack of an effect of PGE(2)
      on VEGF receptors mRNA expression was observed. TNFalpha was able to
      significantly stimulate VEGF release from cells obtained in the mid- and late
      luteal phase or during early pregnancy. All tested doses enhanced mRNA levels of
      VEGF 120 isoform, but not VEGF 164. Additionally, TNFalpha was able to decrease
      Flk-1/KDR mRNA expression, whereas Flt-1 mRNA levels were not affected. These
      results indicated that PGE(2) and TNFalpha influenced VEGF ligand-receptor system
      expression in porcine luteal cells and may therefore play an important role in
      regulation of luteal functions during the estrous cycle and pregnancy in pigs.

PMID- 18324671
TI  - Germ cell-specific expression of GFP gene induced by chicken vasa homologue (Cvh)
      promoter in early chicken embryos.
AB  - In the present study, we cloned the promoter sequence of the chicken vasa
      homologue (Cvh) gene, and observed the induction of germ cell-specific gene
      expression regulated by Cvh promoter in vitro and in vivo. The 2,718-bp Cvh
      promoter sequence involved putative binding sites of transcription factors such
      as Oct-1, Nkx2-5, HNF-4 and v-Myb, and a putative CpG island. The reporter
      vectors, which expressed humanized recombinant green fluorescent protein (hrGFP)
      under the control of one of three lengths (827, 1,555 and 2,718 bp) of Cvh
      promoter, were transfected to the dispersed gonadal cells of 7-day incubated
      embryos in vitro. Every length of promoter-induced germ cell-specific hrGFP
      expression was verified by immunohistochemistry for germ cell-specific antigens,
      and the intensity of fluorescence was significantly higher in the transfected
      gonadal cells using 1,555- and 2,718-bp Cvh promoter compared with 827-bp
      promoter. These results suggested that the germ cell-specific and enhanced gene
      expression required at least a 1,555-bp sequence of the 5' flanking region of Cvh
      gene. In vivo transfection of the reporter vector with 1,555-bp Cvh promoter,
      which was performed by injecting liposome-DNA complex into the blood vessels of 2
      day incubated embryos, also induced germ cell-specific hrGFP expression. The Cvh
      promoter could provide the basis for a methodology for the visualization,
      purification and genetical modification of germ cells, and might further
      contribute to our understanding of the development, proliferation, migration and
      differentiation of germ cells in the chicken.

PMID- 18324672
TI  - Anti-apoptotic effect of melatonin on preimplantation development of porcine
      parthenogenetic embryos.
AB  - In the present study, we investigated the effect of melatonin on the
      preimplantation development of porcine parthenogenetic and somatic cell nuclear
      transfer (SCNT) embryos. Parthenogenetic embryos were cultured in mNCSU-23
      supplemented with various concentrations of melatonin for 7 days. The results
      revealed that 100 pM was the optimal concentration, which resulted in
      significantly increased cleavage and blastocyst formation rates. Additionally,
      100 pM melatonin provided the highest increase in total cell number of
      blastocysts. Therefore, the subsequent experiments were performed with 100 pM
      melatonin. ROS level in 2-8 cell stage embryos in the presence or absence of
      melatonin was evaluated. Embryos cultured with melatonin showed significantly
      decreased ROS. Blastocysts cultured with melatonin for 7 days were analyzed by
      the TUNEL assay. It was observed that melatonin not only increased (P < 0.05) the
      total cell number but also decreased (P < 0.05) the rate of apoptotic nuclei.
      Blastocysts cultured with melatonin were assessed for the expression of apoptosis
      related genes Bcl-xl and Bax, and of pluripotency marker gene Oct-4 by real-time
      quantitative PCR. Analysis of data showed that the expression of Bcl-xl was
      higher (1.7-fold) compared to the control while the expression of Bax was
      significantly decreased relative to the control (0.7-fold) (P < 0.05). Moreover,
      the expression of Oct-4 was 1.7-fold higher than the control. These results
      indicated that melatonin had beneficial effects on the development of porcine
      parthenogenetic embryos. Based on the findings of parthenogenetic embryos, we
      investigated the effect of melatonin on the development of porcine SCNT embryos.
      The results also demonstrated increased cleavage and blastocyst formation rates,
      and the total cell numbers in blastocysts were significantly higher when the
      embryos were cultured with melatonin. Therefore, these data suggested that
      melatonin may have important implications for improving porcine preimplantation
      SCNT embryo development.

PMID- 18324673
TI  - Cis-acting elements (E-box and NBE) in the promoter region of three maternal
      genes (Histone H1oo, Nucleoplasmin 2, and Zygote Arrest 1) are required for
      oocyte-specific gene expression in the mouse.
AB  - We examined the promoter activities of three mouse maternal genes (H1oo, Npm2,
      and Zar1) in oocytes and pre-implantation embryos, and examined the promoters for
      cis-acting elements of 5'-flanking region to obtain the best promoter for
      inducing oocyte-specific gene expression. For the assay, we injected firefly
      luciferase gene constructs under the control of the promoters into the oocytes
      and embryos. Each promoter region showed transcriptional activity in oocytes, but
      not in fertilized embryos. Deletion analysis showed that a putative E-box region
      at position -72 of the H1oo promoter and at the -180 of the Npm2 promoter were
      required for basal transcriptional activity in oocytes. Moreover, a putative NBE
      motif (NOBOX DNA binding elements) (-1796) was shown to enhance basal
      transcriptional activity of the Npm2 promoter. Thus, the E-box and/or NBE may be
      key regulatory regions for the expression of the examined maternal genes (H1oo
      and Npm2) in growing mouse oocytes.

PMID- 18324674
TI  - Inhibition of a novel sperm gelatinase in prawn sperm by the male reproduction
      related Kazal-type peptidase inhibitor.
AB  - Previously, we have identified and characterized a male reproduction-related
      kazal-type peptidase inhibitor (MRPINK) gene from the prawn, Macrobrachium
      rosenbergii. In the present study, MRPINK was discovered to have an inhibitory
      effect on the gelatinolytic activity of M. rosenbergii sperm and
      immunofluorescence analysis revealed it bound specifically onto the base of
      sperm. The proteolytic activity of sperm extracts to vitelline coat components
      was also detected to be interfered by MRPINK. Furthermore, a novel gelatinase on
      sperm was found to be specifically inhibited by MRPINK and was named M.
      rosenbergii sperm gelatinase (MSG). MSG was then isolated and purified by
      reversed-phase high performance liquid chromatography combining with
      gelatinolytic assay. By amino-terminal amino acid sequence analysis and molecular
      cloning, the primary structure of MSG was determined. The data presented in this
      study provided evidence that MRPINK has an inhibitory effect on the gelatinolytic
      activity as well as proteolytic activity of prawn sperm and specifically blocks
      the activity of MSG.

PMID- 18324675
TI  - Genetic changes and DNA damage responses in the prostate.
AB  - The integrity of genomic DNA is challenged by genotoxic stress originating during
      normal cellular metabolism or by external insults. Cellular responses to DNA
      damage involve elegant checkpoint cascades enforcing cell cycle arrest, damage
      repair, apoptosis or cellular senescence. The loss or alterations of genes
      involved in the damage response pathways have been reported in many cancer
      susceptibility syndromes and in sporadic tumors. Furthermore, this surveillance
      pathway is activated during early tumourigenesis presumably due to uncontrolled
      replicative cycles and has been recognized as one of the main barriers against
      the development of cancer. This review discusses the relevance of prostatic
      epithelial cells in prostate tumourigenesis and highlights common molecular
      changes associated with prostate cancer. Furthermore, DNA damage responses of
      primary cultures of human prostatic epithelial cells and fresh human prostate
      tissues are discussed providing evidence for alterations in crucial DNA damage
      checkpoint molecules. New insights connecting prostate tumourigenesis to
      alterations and defects in the pathways maintaining genomic integrity will be
      discussed.

PMID- 18324676
TI  - RANKL inhibition is an effective adjuvant for docetaxel in a prostate cancer bone
      metastases model.
AB  - BACKGROUND: Docetaxel induces an anti-tumor response in men with advanced
      prostate cancer (PCa); however, the side effects associated with docetaxel
      treatment can be severe, resulting in discontinuation of therapy. Thus,
      identification of an effective adjuvant therapy to allow lower doses of docetaxel
      is needed. Advanced PCa is typically accompanied by skeletal metastasis. Receptor
      activator of NFkB ligand (RANKL) is a key pro-osteoclastic factor. Targeting
      RANKL decreases establishment and progression of PCa growth in bone in murine
      models. METHODS: The efficacy of inhibiting RANKL, using a recombinant soluble
      RANK extracellular domain fused with the immunoglobulin Fc domain (RANK-Fc), was
      tested as an adjuvant therapy with docetaxel for PCa bone metastasis in a murine
      intra-tibial model. RESULT: The combination of RANK-Fc and docetaxel reduced
      tumor burden in bone greater than either treatment alone. CONCLUSION: The
      combination of docetaxel with a RANKL-inhibiting agent merits further
      investigation for treatment of advance PCa.

PMID- 18324677
TI  - Prevalence and significance of occult hepatitis B in a liver transplant
      population with chronic hepatitis C.
AB  - Occult hepatitis B virus (HBV) infection is defined as the detection of HBV
      deoxyribonucleic acid (DNA) in the serum or liver tissue of individuals who test
      negative for hepatitis B surface antigen (HBsAg). We undertook a prospective
      study to evaluate the significance and course of occult HBV in patients with
      hepatitis C virus (HCV) cirrhosis undergoing orthotopic liver transplantation
      (OLT). A sensitive real-time polymerase chain reaction assay was utilized to test
      for serum HBV DNA at enrollment and for hepatic HBV DNA within the explant liver.
      Patients were followed with serum HBsAg and HBV DNA post-OLT. A total of 56
      patients with HCV cirrhosis were enrolled between October 2002 and July 2004; of
      these, 44 underwent OLT. The overall prevalence of occult HBV based on positive
      serum HBV DNA was 16 of 56 (28%), and based on positive hepatic HBV DNA ("occult
      HBV liver") was 22 of 44 (50%). The presence of serum hepatitis B core antibody
      (anti-HBc) and a past history of injection drug use correlated with occult
      HBV.Explant-proven hepatocellular carcinoma (HCC) was found in 13 of 22 (59%)
      patients with occult HBV liver compared to 8 of 22 (36%) patients without occult
      HBV liver (P 1/4 0.36, odds ratio 2.5; confidence interval 0.76-8.54 [corrected].
      Post-OLT, no cases of HBV reactivation were noted, and there was no significant
      association between occult HBV and recurrent HCV. In conclusion, occult HBV is
      far more prevalent in patients with end-stage HCV than would be expected from its
      prevalence in the general population. Occult HBV infection is strongly associated
      with the presence of anti-HBc, history of injection drug use, and explant-proven
      HCC.

PMID- 18324678
TI  - "Distorted into clarity": a methodological case study illustrating the paradox of
      systematic review.
AB  - Systematic review is typically viewed in the health sciences as the most
      objective--that is, rigorous, transparent, and reproducible--method for
      summarizing the results of research. Yet, recent scholarship has shown systematic
      review to involve feats of interpretation producing less certain, albeit
      valuable, results. We found this to be the case when we tried to overcome the
      resistance to synthesis of a set of qualitative and quantitative findings on
      stigma in HIV-positive women. These findings were difficult to combine largely
      because of fuzzy conceptualizations of stigma and the volume of unique
      quantitative findings. Our encounter with findings resistant to synthesis
      heightened our awareness of the extent to which all systematic reviews are
      accomplished by practices that paradoxically "distort [research findings] into
      clarity."

PMID- 18324679
TI  - E-selectin regulates gene expression in metastatic colorectal carcinoma cells and
      enhances HMGB1 release.
AB  - Extravasation of cancer cells is a pivotal step in the formation of hematogenous
      metastasis. Extravasation is initiated by the loose adhesion of cancer cells to
      endothelial cells via an interaction between endothelial selectins and selectin
      ligands expressed by the tumor cells. The present study shows that the
      interaction between recombinant E-selectin (rE-selectin) and colorectal cancer
      (CRC) cells alters the gene expression profile of the cancer cells. A DNA
      microarry analysis indicated that E-selectin-mediated alterations were
      significantly more pronounced in the metastatic CRC variants SW620 and KM12SM
      than in the corresponding non-metastatic local SW480 and KM12C variants. The
      number of genes altered by E-selectin in the metastatic variants was about 10
      fold higher than the number of genes altered in the corresponding local variants.
      Aiming to identify genes involved in CRC metastasis, we focused, by using a DNA
      microarry analysis, on genes that were altered by E-selectin in a similar fashion
      exclusively in both metastatic variants. This analysis indicated that E-selectin
      down regulated (at least by 1.6-folds) the expression of 7 genes in a similar
      fashion, in both metastatic cells. The DNA microarry analysis was validated by
      real time PCR or by RT-PCR. HMGB1 was among these genes. Confocal microscopy
      indicated that E-selectin down regulated the cellular expression of the HMGB1
      protein and enhanced the release of HMGB1 into the culture medium. The released
      HMGB1 in turn, activated endothelial cells to express E-selectin.

PMID- 18324681
TI  - Is there gender bias in nursing research?
AB  - Using data from a consecutive sample of 259 studies published in four leading
      nursing research journals in 2005-2006, we examined whether nurse researchers
      favor females as study participants. On average, 75.3% of study participants were
      female, and 38% of studies had all-female samples. The bias favoring female
      participants was statistically significant and persistent. The bias was observed
      regardless of funding source, methodological features, and other participant and
      researcher characteristics, with one exception: studies that had male
      investigators had more sex-balanced samples. When designing studies, nurse
      researchers need to pay close attention to who will benefit from their research
      and to whether they are leaving out a specific group about which there is a gap
      in knowledge.

PMID- 18324682
TI  - Issues and rules for authors concerning authorship versus acknowledgements, dual
      publication, self plagiarism, and salami publishing.

PMID- 18324683
TI  - Crystal structures of MW1337R and lin2004: representatives of a novel protein
      family that adopt a four-helical bundle fold.

PMID- 18324685
TI  - Review of 64 cases of death in children with Prader-Willi syndrome (PWS).
AB  - Several deaths have been reported in children with Prader-Willi syndrome (PWS)
      following treatment with growth hormone (GH). We collected all of the reports of
      deaths in PWS children, both in treatment and non-treatment groups, analyzed the
      causes of the death and compared the two groups. We conducted an exhaustive
      search for reports using bibliographic databases, toxicology pharmacovigilance
      databases, and personal communications. Sixty-four PWS children (42M/22F) aged
      from a few days to 19 years were identified, 28 received GH treatment. Our
      results show that respiratory disorders were the most common cause of death
      (respiratory insufficiency or infections) which were reported in 61% of the
      children (68% in GH-treated and 55.5% in -untreated patients). We found no
      significant differences in gender, prevalence of obesity or prevalence of sleep
      apnea, between the patients treated with GH and the untreated patients.
      Nevertheless, most of the deaths in GH-treated children (75%) occurred during the
      first 9 months after the initiation of GH treatment. Our analysis shows the high
      frequency of respiratory infections in both GH-treated and -untreated PWS
      children. The first 9 months of GH treatment seems to be a high-risk period
      emphasizing the need for comprehensive care before and during GH treatment.

PMID- 18324686
TI  - Sclerocornea associated with the chromosome 22q11.2 deletion syndrome.
AB  - Reported ocular findings in the 22q11.2 deletion syndrome (which encompasses the
      phenotypes of DiGeorge, velocardiofacial, and Takao (conotruncal-anomaly-face)
      syndromes) have included posterior embryotoxon (prominent, anteriorly displaced
      Schwalbe's line at the corneal limbus or edge), retinal vascular tortuosity,
      eyelid hooding, strabismus, and astigmatism. We present seven 22q11.2 patients
      from multiple centers with sclerocornea, an eye finding previously unreported in
      the literature. Four boys and three girls were identified with sclerocornea,
      systemic DGS/VCFS findings, and fluorescence in situ hybridization (FISH)
      confirmed microdeletion at chromosome 22q11.2. FISH diagnosis was perinatal in
      six patients but at 2 years of age in one child. Sclerocornea was bilateral in
      five patients. Findings included descemetocele (five eyes), microophthalmos (one
      eye), iridocorneal adhesions (one bilateral case), and severe anterior segment
      dysgenesis (one eye). Two patients underwent bilateral corneal transplantation;
      another two were scheduled for possible unilateral transplant. Sclerocornea is a
      static congenital condition in which the cornea is opaque and vascularized and
      resembles the sclera. The novel finding of sclerocornea suggests that a genetic
      locus at 22q11.2 may be involved in anterior segment embryogenesis. In most of
      our patients, the diagnostic process was underway, but in one patient 22q11.2
      deletion was not suspected until after the child had already been undergoing
      treatment for sclerocornea for 2 years. Sclerocornea should be added to the
      clinical manifestations of the 22q11.2 deletion syndrome. Ophthalmologists
      diagnosing sclerocornea in children with systemic findings suggestive of 22q11.2
      deletion should ensure appropriate genetic referral.

PMID- 18324687
TI  - Interstitial deletion of 13q associated with polymicrogyria.
AB  - Interstitial deletion of the long arm of chromosome 13 is a rare condition
      characterized by multiple clinical findings. We report a male dizygotic twin with
      an interstitial deletion of 13q and failure to thrive, hypotonia, polymicrogyria,
      bilateral foci of retinoblastoma, hearing loss, bilateral inguinal hernias,
      submucous cleft palate, and dysmorphic features including a triangular shaped
      face, broad forehead, small chin, prominent eyes, downslanting palpebral
      fissures, and a downturned mouth. Chromosome analysis showed an interstitial
      deletion of chromosome 13 which was confirmed by fluorescence in situ
      hybridization analysis to include the Rb locus, but spare the 13q subtelomeric
      region. The karyotype was 46,XY,del(13)(q14.1q31.2).ish del(13)(RB1-,D13S327+) de
      novo. Breakpoints were further characterized by SNP-based microarray.
      Retinoblastoma tumors are a well-known complication of deletion of the
      retinoblastoma susceptibility gene, located at chromosome 13q14.2. Growth
      retardation is another common feature that has been described in other patients
      with a deletion of 13q. Additionally, this patient had brain findings on MRI
      consistent with bilateral polymicrogyria with predominance of the frontal lobes,
      as well as prominent infratentorial and supratentorial vasculature. There are a
      variety of polymicrogyria syndromes that are distinguished by the cortical
      location of the abnormal folding. Several of the subtypes have known genetic loci
      associated with them. To our knowledge, this is the only report of polymicrogyria
      in association with a deletion of chromosome 13.

PMID- 18324688
TI  - Infrequency of two deletion mutations at the DFNB1 locus in patients and
      controls.

PMID- 18324689
TI  - In search of the psychosis gene in people with Prader-Willi syndrome.
AB  - The two main causes of Prader-Willi syndrome (PWS) are a paternally derived
      deletion in the maternally imprinted 15q11-q13 region or UPD(15)mat. Both
      mechanisms result in a loss of the active paternal contribution to the region.
      The affective psychosis associated with PWS has been found to be mainly confined
      to the propositi with UPD(15)mat rather than to those with a deletion. This
      suggests that the psychosis may be related to the presence of two copies rather
      than a single copy of a gene or genes located in the distal half of the region
      which is paternally imprinted, but maternally active, and whose loss results in
      Angelman syndrome (AS). A large population-based study of PWS allowed the
      identification of 12 people with a 15q11-q13 deletion who had suffered psychotic
      episodes and four adults with UPD(15)mat who so far had not. When these people
      were investigated using microsatellite markers, the 12 with a deletion were found
      to have two maternally derived copies of a narrow region between D15S975 and
      D15S661 making them effectively disomic for these loci. Thus all of the people
      with psychosis had two active copies of any imprinted genes in the region while
      all non-psychotic people (including controls) had only one. Quantitative RT-PCR
      studies suggest that a lack of expression of FLJ33332, either as a result of or
      resulting in gene dysregulation, may be associated with psychosis in PWS.

PMID- 18324690
TI  - Rotaglide facilitation of stent deployment.

PMID- 18324691
TI  - The optimal interval of endoscopic variceal ligation.

PMID- 18324692
TI  - Somatostatin or its analogs and terlipressin: Different evidence levels, Same
      recommendations?

PMID- 18324693
TI  - WIN-R revisited: Response to editorial.

PMID- 18324694
TI  - High energy excimer laser to treat coronary in-stent restenosis in an
      underexpanded stent.
AB  - Balloon refractory calcific coronary plaques remain a technical challenge. Stent
      underexpansion is known as a major cause of restenosis and thrombosis. We report
      a case of in-stent restenosis 5 months after stent suboptimal implantation in a
      noncompliant calcific atherosclerotic plaque which could not be disrupted by
      repeated prolonged high-pressure balloon inflations. High-energy excimer laser
      use altered underlying lesion morphology, allowing full stent apposition.
      Advances in equipment and technique have allowed more frequent use of high energy
      excimer laser technology during percutaneous coronary angioplasty with very low
      rates of complications. Laser technology represents a useful tool to overcome
      resistant lesions during percutaneous coronary interventions.

PMID- 18324695
TI  - Outcome after percutaneous closure of a patent foramen ovale using the Intrasept
      device: a multi-centre study.
AB  - OBJECTIVES: This multi-centre study reports safety and efficacy of percutaneous
      patent foramen ovale (PFO) closure, using the fourth generation Intrasept device.
      BACKGROUND: PFO has been associated with paradoxical embolism and cryptogenic
      stroke. Percutaneous PFO closure seems to reduce the risk for recurrent
      paradoxical thrombo-embolism. Currently, different devices are used for PFO
      closure. METHODS: Patients, who underwent a PFO closure with the Intrasept device
      (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the
      study. The primary endpoint was defined as reoccurrence of stroke, transient
      ischemic attack (TIA), or peripheral thrombo-embolism. Peri-procedural and mid
      term complications were reported. RESULTS: Four-hundred thirty patients (mean age
      50.7 +/- 13.0 years, 231 men) underwent closure. The indications were cryptogenic
      stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The
      median follow-up time was 0.8 years, range 3.9 years. The primary endpoint
      occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral
      embolism. Peri-procedural complications were reported in 11.5% of cases, from
      which 0.2% was defined as major. No severe complications occurred during mid-term
      follow-up. A residual shunt was present in 12.5% of patients who did not suffer
      from a recurrent event, compared to 36.4% of patients who reached the primary
      endpoint (P = 0.04). CONCLUSION: This multi-centre study suggests that
      percutaneous closure of a symptomatic PFO with the fourth generation Intrasept
      device is safe and might be effective to prevent the recurrence of paradoxical
      thrombo-embolic events.

PMID- 18324696
TI  - Recent advances in hemodynamics: noncoronary applications of a pressure sensor
      angioplasty guidewire.
AB  - The use of the pressure sensor coronary guidewire is expanding into the
      peripheral circulation as well as into the realm of valvular heart disease. Small
      mechanistic studies and case reports have described the use of pressure wire
      technology in the renal and femoral arteries as well as in mechanical aortic
      valves. The use of this technology to measure hemodynamically significant
      stenoses in noncoronary locations will be discussed and a review of basic and
      more advanced hemodynamics in relation to problems encountered in clinical
      practice will be provided.

PMID- 18324697
TI  - Progress in the retrograde approach for chronic total coronary artery occlusion:
      a case with successful angioplasty using CART and reverse-anchoring techniques 3
      years after failed PCI via a retrograde approach.
AB  - After the introduction of the retrograde approach in percutaneous coronary
      intervention for chronic total occlusion (CTO), different kinds of strategies and
      techniques have been developed in order to achieve final success. However, it has
      not been fully demonstrated whether these strategies and techniques can really
      improve the final result. We observed one case, for which the initial attempt of
      the retrograde approach for a CTO lesion was unsuccessful despite the successful
      approach of a retrograde guidewire to the lesion, and with the second retrograde
      approach 3 years later being eventually successful by using various kinds of
      strategies and techniques. This case clearly demonstrates how the final success
      through the retrograde approach can be achieved by using a combination of the
      improved strategies and techniques for CTO lesions.

PMID- 18324698
TI  - A novel approach for quantitative analysis of intracoronary optical coherence
      tomography: high inter-observer agreement with computer-assisted contour
      detection.
AB  - OBJECTIVE: This study aims to examine observer-related variability of
      quantitative optical coherence tomography (OCT) derived measurements from both in
      vitro and in vivo pullback data. BACKGROUND: Intravascular OCT is a new imaging
      modality using infrared light and offering 10 times higher image resolution (15
      microm) compared to intravascular ultrasound. The quantitative analysis of in
      vivo intracoronary OCT imaging is complicated by the presence of blood, motion
      artifacts and the large quantity of information that has to be processed.
      METHODS: We developed a standardized, automated quantification process for
      intracoronary OCT pullback data with inter-observer variability assessed both in
      vitro by using postmortem human coronary arteries and in vivo by studying simple
      and complex coronary pathology and outcomes following stent implantation. The
      consensus between measurements by two observers was analyzed using the intraclass
      and interclass correlation coefficient and the reliability coefficients. Bland
      Altman plots were generated to assess the relationship between variability and
      absolute measurements. RESULTS: In vitro OCT assessment was performed in nine
      postmortem coronary arteries. The time needed for semiautomated contour detection
      of a 15-mm long coronary segment was approximately 40 min. The absolute and
      relative difference between lumen area measurements derived from two observers
      was low [0.02 +/- 0.10 mm(2); (0.3 +/- 0.5)% respectively] with excellent
      correlation confirmed by linear regression analysis (R(2) = 0.99; P < 0.001).
      Similarly, in vivo measurements demonstrated a high correlation with the main
      source of inter-observer variation occurring as a result of coronary dissection
      and motion artifact. The absolute and relative difference between measurements
      were 0.11 +/- 0.33 mm(2) (1.57 +/- 0.05)% for lumen area (R(2) = 0.98; P <
      0.001), 0.17 +/- 0.68 mm(2) (1.44 +/- 0.08)% for stent area (R(2) = 0.94; P <
      0.001), and 0.26 +/- 0.72 mm(2) (14.08 +/- 0.37)% for neointimal area (R(2) =
      0.78; P < 0.001). CONCLUSIONS: Highly accurate computer-assisted quantitative
      analysis ofintracoronary OCT pullbacks is feasible with low inter-observer
      variability. The presented approach allows for observer independent analysis of
      detailed vessel structures, and may be a valuable tool for future longitudinal
      studies incorporating OCT.

PMID- 18324699
TI  - Methods to reduce patients' maximum skin dose during percutaneous coronary
      intervention for chronic total occlusion.
AB  - OBJECTIVES: The purpose of this research is to assess the patient's entrance skin
      dose (ESD) during percutaneous coronary intervention (PCI) for chronic total
      occlusion (CTO), and discuss methods to reduce the maximum ESDs. BACKGROUND: Only
      a few reports are available on the methods to reduce patients' maximum ESD during
      the procedures. METHODS: This study included consecutive 30 patients who
      underwent PCI procedures for CTO in the three institutions. Pearson correlation
      test was employed to determine the relationship between total fluoroscopic time
      (TFT) and the maximum ESD, dose area product (DAP) value, and the maximum ESD in
      each institution. RESULTS: There were significant correlations between the TFT
      and maximum ESD (Institution 1: P = 0.000410, Institution 2: P = 0.000525), and
      between the DAP and the maximum ESD (Institution 2: P < 0.0001). In Institution
      1, TFT of 60 min was set as the upper limit, and the maximum ESDs were controlled
      within 7 Gy. In Institution 2, the angiographic unit was a biplane system, and
      two skin sites were exposed, corresponding to the angulation of each X-ray tube.
      In Institution 3, the interventionalist changed the beam angulations frequently
      by several degrees during the procedures, and the maximum ESD was controlled
      within 3 Gy even during procedures with a TFT of more than 1 hr. CONCLUSIONS: The
      TFT and DAP, the latter of which is preferable, are useful to estimate the
      maximum ESD. Limiting the TFT or DAP, or changing the beam angulations is
      important to control ESD during prolonged procedures.

PMID- 18324700
TI  - Addressing the hemodynamic dilemma of combined mitral and aortic stenosis.
AB  - Accurate assessment of valvular hemodynamics is essential in the decision-making
      process when referring a patient for cardiac surgery who has suspected coexistent
      aortic and mitral valve disease. Often times, one valvular lesion is worse than
      the other, and the question of "prophylactically" replacing the less severe valve
      at the time of surgery is controversial. In these situations and because of
      uncertainty regarding noninvasive assessment, hemodynamic evaluation in the
      cardiac catheterization laboratory provides critical information in guiding
      therapy.

PMID- 18324701
TI  - Hybrid treatment of a symptomatic popliteal pseudoaneurysm due to type-I endoleak
      after previous endovascular exclusion.
AB  - PURPOSE: The development of endovascular repair of popliteal aneurysms has
      provided an alternative, minimally invasive way of treatment. We present a case
      of a late type-I endoleak, after previous exclusion of a popliteal
      pseudoaneurysm, leading to rupture and massive hematoma, which was excluded in a
      hybrid procedure. CASE REPORT: A 95-year-old woman presented with progressive
      swelling with skin ulceration and necrosis cranial to the medial side of her left
      knee. Four years earlier, a left popliteal pseudoaneurysm was excluded with a
      stent-graft. Rupture of the popliteal artery with massive hematoma was
      demonstrated by ultrasound examination and a spiral computed tomography scan,
      with high suspicion of a type-I endoleak. Endovascular repair of the endoleak
      with a polytetrafluoroethylene-covered stent-graft was followed by surgical
      resection of the damaged skin and evacuation of the hematoma. CONCLUSION: Type-I
      endoleaks after endovascular exclusion of popliteal pseudoaneurysms do occur and
      may lead to rupture. A symptomatic pseudoaneurysm may be successfully treated by
      a hybrid procedure.

PMID- 18324702
TI  - Evaluation of total quinolizidine alkaloids content in lupin flours, lupin-based
      ingredients, and foods.
AB  - Lupin proteins are gaining attention to replace animal proteins and other plants
      ingredients in several foods such as bakery products, imitation dairy and meat
      products, and beverages. One of the major safety issues of lupin-based foods is
      the presence of quinolizidine alkaloids (QAs), bitter compounds produced by lupin
      plants as a defense mechanism against predators. In mammals, QA intoxication is
      characterized by trembling, shaking, excitation, and convulsion. Lupanine and
      sparteine, the most common QAs, show acute oral toxicity due to neurological
      effects leading to the loss of motor co-ordination and muscular control. In this
      paper, 27 samples of lupin-based products, i. e., flours, protein isolates, and
      food (either model or commercially available ones), were analyzed for evaluating
      the QA content using a method based on GC/MS. All the analyzed samples were safe
      since they respect the maximum limit of 200 mg/kg fixed by the Health Authorities
      of Australia, New Zealand, Great Britain, and France, that have regulated this
      topic. The QA contents were particularly low in protein isolates and in foods
      containing these ingredients, indicating that their use is a very effective tool
      for keeping low the daily intake of QAs.

PMID- 18324703
TI  - Puma is a novel target of soy isoflavone genistein but is dispensable for
      genistein-induced cell fate determination.
AB  - Here, we attempted to identify novel target genes of genistein in human A549
      cells. Using analysis of proteins related to cell cycle and apoptotic pathways,
      we confirmed an elevated level of p53 accompanying p21 Waf1/Cip1 protein in
      genistein-treated or genistin-treated A549 and WI-38 cells, but not in HeLa
      cells. In addition, a p53-upregulated modulator of apoptosis (Puma) protein
      accumulated significantly in genistein-treated A549 and WI-38 cells, but not in
      genistin-treated or beta-estradiol-treated cells, though the growth of any
      ingredient-treated cells was severely inhibited. Intriguingly, the caspase-3
      activity of genistein-treated A549 cells, in which Puma or p53 expression was
      knocked-down by RNA interference (RNAi), remained unaltered compared to that in
      cells transfected with irrelevant RNAi. These results raise a concern that
      molecular targets identified by powerful omic approaches may not necessarily
      represent key molecules responsible for given cellular phenotypes and thus must
      be verified by conclusive assays.

PMID- 18324704
TI  - The potential of sphingomyelin as a chemopreventive agent in AOM-induced colon
      cancer model: wild-type and p53+/- mice.
AB  - A protective effect of sphingolipids on colorectal cancer (CRC) has been reported
      in certain mouse strains. It is unknown if sphingolipids are protective in a p53
      deficiency mouse model of CRC. This study investigated the effect of
      sphingomyelin (SM) on intestinal sphingomyelinase (SMase) activity, colonic
      epithelial biology and azoxymethane (AOM)-induced CRC. Groups of wild-type
      (C57BL/6J) and p53+/- mice were fed 0.1% SM diet for 4 wk, administered a single
      AOM injection and then killed 6 h later to measure apoptosis and proliferation.
      Separately, both mouse types were fed 0.05% SM diet, administered three AOM
      injections and killed 33-38 wk later to measure tumour formation. SM
      significantly increased SMase activity and reduced proliferation (p < 0.05) in
      wild-type and p53+/- mice. SM did not regulate baseline apoptosis, apoptotic
      response to AOM or apoptosis in tumours, nor did it restore defective apoptosis
      in p53+/- mice. There was a nonsignificant trend to reduced tumour incidence with
      SM in wild-type (p = 0.15) and p53+/- (p = 0.12) mice. In conclusion, while
      increasing intestinal SMase activity and suppressing proliferation, SM did not
      promote any form of apoptosis and failed to achieve significant protection in
      these mice. Further investigation to understand the variable effect of SM in
      preventing CRC is warranted.

PMID- 18324705
TI  - Nutritional concerns in pediatric inflammatory bowel disease patients.
AB  - In approximately one-fourth of patients with Crohn's disease (CD) and ulcerative
      colitis (UC), disease onset occurs during childhood and adolescence. In addition
      to gastrointestinal and extraintestinal symptoms of inflammatory bowel disease
      (IBD), children with these conditions often experience one or more nutritional
      complications of their disease including growth failure, delayed puberty,
      osteoporosis, anemia, and micronutrient deficiencies. This article provides an
      overview of the epidemiology, pathophysiology, evaluation, and management of
      selected nutritional complications in pediatric IBD.

PMID- 18324706
TI  - Predicting interactions between conventional medications and botanical products
      on the basis of in vitro investigations.
AB  - The potential for various natural products to perturb the metabolism and
      disposition of medications has been recognized for decades. There are numerous in
      vitro and in vivo methods available to screen botanical products for drug
      interaction potential. Although many normal volunteer botanical-drug interaction
      studies have been performed, clearly, in vitro studies assessing the potential
      for drug interactions with various natural products represent the predominant
      type of published research performed to date. In addition to the recognized
      limitations of in vitro screening methodologies to assess conventional drug
      interactions, further difficulties emerge when examining botanical products.
      Primary challenges include assigning hepatic concentrations and accounting for
      bioavailability, distribution, first-pass metabolism and active metabolites.
      Additionally, variability in the chemical composition of commercially available
      botanical supplements, the lack of analytical standards and the inability to
      accurately screen the entities as mixtures add to complexities in experimental
      design. This mini-review is intended to address the particular problems and
      challenges in evaluating botanical supplements using in vitro methods, and review
      what can and cannot be learned from such investigations.

PMID- 18324707
TI  - Free Zn(2+) enhances inhibitory effects of EGCG on the growth of PC-3 cells.
AB  - Epigallocatechin-3-gallate (EGCG), a major component of green tea, has both
      preventive and therapeutic beneficial actions in prostate cancer. In the present
      study, we compared the growth inhibitory effects and the antioxidant and ability
      to modify cell membrane permeation of zinc-EGCG complex and Zn2+/EGCG mixture on
      androgen-insensitive prostate cancer (PC-3) cells. It was noted that free Zn2+
      enhanced the growth inhibitory effects of EGCG on PC-3 cells at 160 micromol/L
      concentration,whereas zinc-EGCG complex was ineffective. EGCG showed potent free
      radical scavenging ability in the presence of Zn2+. EGCG in the presence of Zn2+
      was more effective than EGCG alone in enhancing the permeability of the cell
      membrane, whereas zinc-EGCG complex had no effect on PC-3 cell membrane
      permeability. These results indicate that though Zn2+ enhanced the action of EGCG
      on PC-3 cells, zinc-EGCG complex is highly unlikely to be formed in the presence
      of Zn2+ and EGCG to explain the potentiating action of Zn2+ on the growth
      inhibitory property of EGCG on PC-3 cells.

PMID- 18324708
TI  - Time-course regulation of quercetin on cell survival/proliferation pathways in
      human hepatoma cells.
AB  - Quercetin, a dietary flavonoid, has been shown to possess anticarcinogenic
      properties, but the precise molecular mechanisms of action are not thoroughly
      elucidated. This study was aimed at investigating the time-course regulation
      effect of quercetin on survival/proliferation pathways in a human hepatoma cell
      line (HepG2). Quercetin induced a significant time-dependent inactivation of the
      major survival signaling proteins, i. e., phosphatidylinositol 3-kinase (PI 3
      kinase)/protein kinase B (AKT), extracellular regulated kinase (ERK), protein
      kinase C-alpha (PKC-alpha), in concert with a time-dependent activation of key
      death-related signals: c-jun amino-terminal kinase (JNK) and PKC-delta. These
      data suggest that quercetin exerts a tight regulation of survival/proliferation
      pathways that requires the integration of different signals and persists over
      time, being the balance of these regulatory signals what determines the fate of
      HepG2 cells.

PMID- 18324713
TI  - Opening opportunities for new drugs against neglected diseases.

PMID- 18324715
TI  - N-myristoyltransferase: a prospective drug target for protozoan parasites.

PMID- 18324717
TI  - Trends in biological optical microscopy.

PMID- 18324718
TI  - Enhancing fluorescence brightness: effect of reverse intersystem crossing studied
      by fluorescence fluctuation spectroscopy.
AB  - Experiments based on fluorescence detection are limited by the population of the
      fluorescence marker's long-lived dark triplet state, leading to pronounced
      photobleaching reactions and blinking which reduces the average fluorescence
      signal obtained per time interval. By irradiation with a second, red-shifted
      laser line, we initiate reverse intersystem crossing (ReISC) which enhances the
      fluorescence signal of common fluorophores up to a factor of 14. The reverse
      intersystem crossing from the triplet state back to the singlet system is
      achieved by photoexcitation to higher-excited triplet states, which are, however,
      prone to photobleaching. We gain insights into the competing pathways of ReISC
      and photobleaching. The relative efficiencies of these two pathways and the
      triplet lifetime determine the achievable fluorescence enhancement, which varies
      strongly with the choice of dye, excitation irradiance and wavelength, and with
      environmental conditions. The study of ReISC not only results in a better
      understanding of a fluorescent label's photophysics, but the method is a possible
      approach to optimize fluorescence emission in experiments, where signal strength
      is a critical parameter.

PMID- 18324719
TI  - Predicting NMR relaxation rates in anisotropically tumbling proteins through
      networks of coupled rotators.
AB  - We show that the prediction of (15)N relaxation rates in proteins can be extended
      to systems with anisotropic global rotational diffusion by using a network of
      coupled rotators (NCR), starting from a three-dimensional structure. The
      relaxation rates predicted by this method are confronted in several examples with
      experiments performed by other groups. The NCR spectral density functions are
      compared with the results obtained from reduced spectral density mapping. The
      consequence of the timescales of internal motions on the predicted relaxation
      rates and the effects of the predicted local anisotropy-present only in the case
      of anisotropic overall tumbling-on dynamic parameters, are discussed.

PMID- 18324720
TI  - Photophysical properties of heteroleptic iridium complexes containing carbazole
      functionalized beta-diketonates.
AB  - Twelve iridium complexes with general formula of Ir(C;N)(2)(LX) [C;N represents
      the cyclometalated ligand, i.e. 2-(2,4-difluorophenyl) pyridine (dfppy), 2
      phenylpyridine (ppy), dibenzo{f, h}quinoxaline (DBQ); LX stands for beta
      diketonate, i.e. acetyl acetonate (acac), 1-(carbazol-9-yl)-5,5-dimethylhexane
      2,4-diketonate (CBDK), 1-(carbazol-9-yl)-5,5,6,6,7,7,7-heptafluoroheptane-2,4
      diketonate (CHFDK), 1-(N-ethyl-carbazol-3-yl)-4,4,5,5,6,6,6-heptafluorohexane-1,3
      diketonate (ECHFDK)] are synthesized, characterized and their photophysical
      properties are systemically studied. In addition, crystals of Ir(DBQ)(2)(CHFDK)
      and Ir(DBQ)(2)(acac) are obtained and characterized by single crystal X-ray
      diffraction. The choice of these iridium complexes provides an opportunity for
      tracing the effect of the triplet energy level of ancillary ligands on the
      photophysical and electrochemical behaviors. Data show that if the triplet energy
      level of the beta-diketonate is higher than that of the Ir(C;N)(2) fragment and
      there is no superposition on the state density map, strong (3)LC or (3)MLCT-based
      phosphorescence can be obtained. Alternatively, if the state density map of the
      two parts are in superposition, the (3)LC or (3)MLCT-based transition will be
      quenched at room temperature. Density functional theory calculations show that
      these complexes can be divided into two categories. The lowest excited state is
      mainly determined by C;N but not beta-diketonate when the difference between the
      triplet energy levels of the two parts is large. However, when this difference is
      very small, the lowest excited state will be determined by both sides. This
      provides a satisfactory explanation for the experimental observations.

PMID- 18324721
TI  - Large scale depletion of the high-abundance proteins and analysis of middle- and
      low-abundance proteins in human liver proteome by multidimensional liquid
      chromatography.
AB  - An unbiased method for large-scale depletion of high-abundance proteins and
      identification of middle- or low-abundance proteins by multidimensional LC (MDLC)
      was demonstrated in this paper. At the protein level, the MDLC system, coupling
      the first dimensional strong cation exchange (SCX) chromatography with the second
      dimensional RP-HPLC, instead of immunoaffinity technology, was used to deplete
      high-abundance proteins. Sixty-two fractions from SCX were separated further by
      RPLC. UV absorption spectra were observed to differentiate high-abundance
      proteins from middle- or low-abundance proteins. After the depletion of high
      abundance proteins, middle- or low-abundance proteins were enriched, digested,
      and separated by online 2D-micro-SCX/cRPLC. The eluted peptides were deposited on
      the MALDI target and detected by MALDI-TOF/TOF MS. This depletion strategy was
      applied to the proteome of the normal human liver (NHL) provided by the China
      Human Liver Proteome Project (CHLPP). In total, 58 high-abundance proteins were
      depleted in one experiment. The strategy increases greatly the number of
      identified proteins and around 1213 proteins were identified, which was about 2.7
      times as that of the nondepletion method.

PMID- 18324722
TI  - Protein labeling and biotinylation of peptides during spot synthesis using biotin
      p-nitrophenyl ester (biotin-ONp).
AB  - Biotin-labeled peptides are used for numerous biochemical and microbiological
      applications. Due to the strong affinity of biotin to streptavidin, the detection
      of biotinylated molecules is very sensitive. A powerful technique for parallel
      synthesis and high-throughput screening of peptides is the spot synthesis. One
      example for the use of spot synthesis is the screening of biotinylated peptides
      synthesized on cellulose membranes, which is particularly favorable for the
      investigation of protease cleavage sites. Additionally, in combination with
      biotinylated protein samples, the spot technique can be used for investigations
      of peptide-protein and protein-protein interactions. Here, we present our results
      of the use biotin p-nitrophenyl ester (biotin-ONp) in spot synthesis and as a
      reagent for biotin-labeling of protein samples.

PMID- 18324723
TI  - Proteomic profiling reveals that Th2-inducing dendritic cells stimulated with
      helminth antigens have a 'limited maturation' phenotype.
AB  - Dendritic cells (DCs) are important in the initiation of primary immune responses
      against pathogens. To aid understanding of how DCs guide T helper (Th)2-type
      responses, we employed 2-DE in association with MS/MS to identify proteins which
      characterise pro-Th2 DCs (matured with zero-to-three hours released proteins (0
      3hRP), released by Schistosoma mansoni cercariae) versus pro-Th1 DCs (matured
      with lipopolysaccharide, LPS) and immature DCs. Software analysis of average 2-DE
      gels (three replicates per DC type) showed many similarities in the pattern of
      spots between the three groups of DCs but also marked changes. The major and
      significant changes in protein expression mainly affected cytoskeletal proteins.
      Other differences included chaperone proteins and enzymes involved in protein
      folding, S100 calcium-binding proteins, peroxiredoxin 1, superoxide dismutase 1,
      several annexins and arginase 1. Our study demonstrates that pro-Th2 DCs matured
      with 0-3hRP exhibit a proteome that is intermediate between that of immature DCs
      and pro-Th1 DCs. Finally, the differential regulation of protein spots identified
      by MALDI-MS/MS as having cytoskeletal and morphological functions was confirmed
      by contrast, confocal and scanning electron microscopy examination of DCs.
      Together, our results support the view that Th2 differentiation results from a
      'limited maturation' of DCs.

PMID- 18324724
TI  - A label-free quantification method by MS/MS TIC compared to SILAC and spectral
      counting in a proteomics screen.
AB  - In order to assess the biological function of proteins and their modifications
      for understanding signaling mechanisms within cells as well as specific
      biomarkers to disease, it is important that quantitative information be obtained
      under different experimental conditions. Stable isotope labeling is a powerful
      method for accurately determining changes in the levels of proteins and PTMs;
      however, isotope labeling experiments suffer from limited dynamic range resulting
      in signal change ratios of less than approximately 20:1 using most commercial
      mass spectrometers. Label-free approaches to relative quantification in
      proteomics such as spectral counting have gained popularity since no additional
      chemistries are needed. Here, we show a label-free method for relative
      quantification based on the TIC from peptide MS/MS spectra collected from data
      dependent runs can be used effectively as a quantitative measure and expands the
      dynamic range over isotope labeling experiments allowing for abundance
      differences up to approximately 60:1 in a screen for proteins that bind to
      phosphotyrosine residues.

PMID- 18324725
TI  - Speciation of magnesium in rat plasma using capillary electrophoresis-inductively
      coupled plasma-atomic emission spectrometry.
AB  - A new method for speciation analysis of magnesium species and quantification of
      free magnesium concentrations in rat plasma was developed by on-line coupling of
      CE with inductively coupled plasma-atomic emission spectrometry (ICP-AES).
      Baseline separation of seven magnesium species was achieved by using a 120 cm
      (100 microm internal diameter) fused-silica capillary, a 20 kV separation voltage
      and a solution of 50 mmol/L NaAc-HAc (pH 5.5) as electrolyte buffer. CE-ICP-AES
      analysis of a rat plasma sample showed the presence of seven magnesium species,
      one of which was identified as free Mg2+ ion by spiking a Mg2+ standard; the
      migration time of the Mg2+ peak in the standard and the spiked sample matched
      with each other. One protein-bound magnesium species in rat plasma is associated
      with albumin, and the other three species are combined with globulin. The
      concentration of free magnesium in the plasma was 14.0 mg/L. The other six
      magnesium species were estimated to be 4-15 mg/L. RSDs of migration time and peak
      area for the magnesium species from ten replicates were less than 5%. The
      developed method was also applied to speciation analysis of magnesium species in
      spiked plasma samples. The recoveries of the free magnesium species in four
      samples ranged from 95.8 to 103.8%.

PMID- 18324726
TI  - Identification of new regional marker proteins to map mouse brain by 2-D
      difference gel electrophoresis screening.
AB  - To screen for new region-specific protein markers we compared the proteome maps
      of the primary visual and somatosensory areas V1 and S1 in mouse brain using 2-D
      difference gel electrophoresis (2-D DIGE). Twenty-three protein spots showed a
      statistically significant difference in expression level between V1 and S1, with
      52% appearing more abundantly in V1. Twenty-six proteins were mass
      spectrometrically identified in 22 spots. To assess the validity of this list of
      potential areal markers generated by 2-D DIGE, the effective area-specific
      distribution profile of creatine kinase brain subtype (CKB), a protein with a
      clearly higher expression level in S1, was monitored with in situ hybridization.
      The mRNA expression profile of CKB displayed a clear area-specific distribution,
      which allowed demarcation of S1 and its topographical borders with neighboring
      neocortical areas. This proteomic study demonstrates the innovative application
      of 2-D DIGE and MS to select new regional markers for neuroscience research.

PMID- 18324727
TI  - The first contribution of capillary electrophoresis to the study of abiotic
      origins of homochirality: investigation of the enantioselective adsorption of 3
      carboxy adipic acid on minerals.
AB  - CE with UV detection was used for the first time to determine the
      enantioselective adsorption of the short-chain tricarboxylic acid, 3-carboxy
      adipic acid, on minerals as a mean of investigating plausible mechanisms for the
      origin of biochemical homochirality on Earth. The use of vancomycine as chiral
      selector in the separation buffer using the partial filling technique enabled the
      separation of the two enantiomers of this organic acid in about 12 min. Taking
      into account that this compound has a low absorption of the UV light, and in
      order to achieve the sensitivity needed to determine the enantiomeric excess of
      samples of 3-carboxy adipic acid adsorbed on minerals, we applied a strategy
      consisting of a field-amplified sample stacking together with the use of a bubble
      capillary and detection at low wavelength (192 nm). This combination enabled an
      LOD of about 10(-7) M and the determination of the enantiomeric excess of 3
      carboxy adipic acid adsorbed on calcite and feldspar mineral samples at
      subnanomol levels of this acid. Results showed that an enantioselective
      adsorption of the enantiomers of 3-carboxy adipic acid on minerals took place.

PMID- 18324728
TI  - The monitoring of nucleotide diphosphate kinase activity by blue native
      polyacrylamide gel electrophoresis.
AB  - Nucleoside diphosphate kinase (NDPK) has been shown to play a pivotal role in
      modulating a plethora of cellular processes. In this study, we report on a blue
      native (BN) PAGE technique which allows the facile assessment of NDPK activity
      and expression. The in-gel detection of NDPK relies on the precipitation of
      formazan at the site of immobilized enzyme activity. This is achieved by coupling
      the formation of ATP, as a consequence of gamma-phosphate transfer from NTP to
      ADP, to hexokinase (HK), glucose-6-phosphate dehydrogenase (G6PDH), oxidized
      nicotinamide adenine dinucleotide phosphate (NADP), phenazine methosulfate (PMS),
      and iodonitrotetrazolium chloride (INT). 2-D denaturing gel analysis confirmed
      that the activity bands corresponded to NDPK as indicated by subunit composition.
      Furthermore, the sensitivity and specificity of this readily accessible procedure
      was assessed by monitoring the in-gel activity of NDPK using different
      concentrations of GTP and CTP as well as deoxynucleoside triphosphates. This
      electrophoretic technique allows the quick and easy detection of NDPK, a
      housekeeping enzyme crucial to cell survival.

PMID- 18324730
TI  - Identification by 2-D DIGE of apoplastic proteins regulated by
      oligogalacturonides in Arabidopsis thaliana.
AB  - Oligogalacturonides (OGs) are elicitors of plant defence responses released from
      the homogalacturonan of the plant cell wall during the attack by pathogenic micro
      organisms. The signalling pathway mediated by OGs remains poorly understood, and
      no proteins involved in their signal perception and transduction have yet been
      identified. In order to shed light into the molecular pathways regulated by OGs,
      a differential proteomic analysis has been carried out in Arabidopsis. Proteins
      from the apoplastic compartment were isolated and their expression compared
      between control and OG-treated seedlings. 2-D gels and difference in gel
      electrophoresis (DIGE) techniques were used to compare control and treated
      proteomes in the same gel. The analysis of subcellular proteomes from seedlings
      allowed the identification of novel and low abundance proteins that otherwise
      remain masked when total cellular extracts are investigated. The DIGE technique
      showed to be a powerful tool to overcome the high interexperiment variation of 2
      D gels. Differentially expressed apoplastic proteins were identified by MS and
      included proteins putatively involved in recognition as well as proteins whose
      PTMs are regulated by OGs. Our findings underscore the importance of cell wall as
      a source of molecules playing a role in the perception of pathogens and provide
      candidate proteins involved in the response to OGs.

PMID- 18324729
TI  - Protein-aptamer binding studies using microchip affinity capillary
      electrophoresis.
AB  - The use of traditional CE to detect weak binding complexes is problematic due to
      the fast-off rate resulting in the dissociation of the complex during the
      separation process. Additionally, proteins involved in binding interactions often
      nonspecifically stick to the bare-silica capillary walls, which further
      complicates the binding analysis. Microchip CE allows flexibly positioning the
      detector along the separation channel and conveniently adjusting the separation
      length. A short separation length plus a high electric field enables rapid
      separations thus reducing both the dissociation of the complex and the amount of
      protein loss due to nonspecific adsorption during the separation process.
      Thrombin and a selective thrombin-binding aptamer were used to demonstrate the
      capability of microchip CE for the study of relatively weak binding systems that
      have inherent limitations when using the migration shift method or other CE
      methods. The rapid separation of the thrombin-aptamer complex from the free
      aptamer was achieved in less than 10 s on a single-cross glass microchip with a
      relatively short detection length (1.0 cm) and a high electric field (670 V/cm).
      The dissociation constant was determined to be 43 nM, consistent with reported
      results. In addition, aptamer probes were used for the quantitation of standard
      thrombin samples by constructing a calibration curve, which showed good linearity
      over two orders of magnitude with an LOD for thrombin of 5 nM at a three-fold
      S/N.

PMID- 18324731
TI  - Strategies to recover proteins from ocular tissues for proteomics.
AB  - We present here the results of protein extraction from different ocular regions
      using different detergents. Extraction strategies used to determine optimal
      protein extraction included: pressure cycling and aqueous-organic phase
      extraction in combination with electrophoretic fractionation for anterior,
      posterior, and peripapillary sclera. Detergent extraction of proteins from
      freshly enucleated porcine eyes (n = 8) showed significant differences for
      different eye regions. Protein yield ranged from 2.3 to 50.7 mug protein/mg for
      different ocular tissues, with the lens yielding the most protein. ASB-14 and
      Triton X-100 provided the best protein yields (n = 10) for anterior and posterior
      sclera. The spectrophotometric measurements for ASB-14 were not consistent with
      SDS-PAGE densitometry. A combination of 0.5% Triton X-100, 0.5% Tween-20, and
      0.1% Genapol C-100 was found optimal for extraction from sclera. Proteins from
      different regions of the eye are best extracted with different detergents. The
      pressure cycling technology provided superior extraction compared to the other
      methods. Additional aqueous-organic phase partitioning enables superior
      fractionation when compared to SDS-PAGE alone. Organic phase fractionation is
      compatible with MS and allowed identification of 34, 71, and 77 proteins
      respectively from anterior, posterior, and peripapillary sclera. The extraction
      strategy may affect the final outcome in protein profiling by MS or by other
      methods.

PMID- 18324732
TI  - Morphogenetic lung defects of JSAP1-deficient embryos proceeds via the
      disruptions of the normal expressions of cytoskeletal and chaperone proteins.
AB  - Recent studies have shown that JNK/stress-activated protein kinase-associated
      protein 1 (JSAP1)-deficient mice die from respiratory failure shortly after
      birth. To understand the underlying mechanism, we investigated the histological
      appearances and cell type changes in developing jsap1(-/-) lungs between E12.5
      and E18.5. At the light microscopic level, no overt abnormality was detected in
      jsap1(-/-) until E16.5. However, alveoli and airway formations that normally
      occur after E16.5 were poorly advanced in jsap1(-/-). Despite these morphological
      defects, surfactant secreting cells labeled by anti-SP-B or anti-SP-C were
      present in normal ranges in jsap1(-/-) lungs. Smooth muscle alpha-actin
      expressing cells were also developed in jsap1(-/-) lungs, although actin
      expression was decreased. The expressions of transcriptional factors, such as,
      nuclear factor Ib (Nfib), N-myc, and octamer transcriptional factor 1 (Oct-1),
      which play a critical role in lung morphogenesis, were found to be down
      regulated, whereas signal transducer and activator of transcription 3 (Stat3),
      sonic hedgehog (Shh), and smoothened (Smo) were up-regulated, in jsap1(-/-) lungs
      at E17.5-E18.5 compared with those in jsap1(+/+) lungs. Proteomics analysis of
      E17.5 lung identified 39 proteins with altered expressions, which included actin,
      tropomyosin, myosin light chain, vimentin, heat shock protein (Hsp27), and Hsp84.
      These results suggest that JSAP1 is required for the normal expressions of
      cytoskeletal and chaperone proteins in the developing lung, and that impaired
      expressions of these proteins might cause morphogenetic defects observed in
      jsap1(-/-) lungs.

PMID- 18324733
TI  - Temporal variations of the postnatal rat urinary proteome as a reflection of
      systemic maturation.
AB  - The rat kidney matures during the first 2 wk of life, suggesting that temporal
      variations in the urinary proteome may occur during this period. We describe the
      urine proteome during postnatal development in the rat and demonstrate specific
      proteomic changes corresponding to developmental milestones. Urine was collected
      from 30 rats at five postnatal (P) days of life (P1, P3, P7, P14, and >P30) by
      bladder aspiration. The proteome was assessed by nano-ESI-LC-MS/MS. For
      identification, we used stringent criteria to provide a 1% false positive rate at
      the peptide level. The proteins in common at each time interval decreased during
      postnatal maturation. When comparing all five developmental times, six proteins
      were ubiquitously present. We detected 14 proteins involved with cellular
      adhesion, structure, or proliferation and differentiation only during neonatal
      development. Additionally, 30 proteins were specific to adults, of which 13
      originated from the prostate or seminal vesicle. This is the first MS
      characterization of the normal urinary proteome in early postnatal rodent
      development that demonstrates distinct differences correlating with different
      stages of tissue maturation. Further characterization of the normal urinary
      proteome may provide the basis for identification of urinary biomarkers of
      diseases of the urinary tract.

PMID- 18324736
TI  - Carbon-13 NMR of fluorocyclopropanes.
AB  - Carbon-13 and hydrogen NMR data are presented for several cyclopropanes with one
      to four fluorine atoms attached to the ring. Substituents directly attached to a
      ring carbon are found to unshield that carbon to an extent increasing with their
      electronegativity, but remote substituents may have an opposite effect. Relative
      orientation of the substituent groups, especially if they are bulky, also has a
      strong influence on the ring-carbon shifts. Chemical shifts of carbons in methyl
      groups attached to the ring change to an extent which is additive in the effects
      of gem and cis substituents. One-bond coupling of ring carbons with fluorines is
      affected both by geminal and vicinal substituents, in a way generally related to
      their electronegativity. It is tentatively concluded that two-bond coupling
      between ring carbons and ring-attached fluorines depends in magnitude primarily
      on what groups are cis to the fluorine. Two-bond coupling between a carbon atom
      in a ring-attached methyl and the hydrogen gem to the methyl appears to be
      vanishingly small, but there is appreciable three-bond coupling of the methyl
      carbons to vicinal hydrogens.

PMID- 18324737
TI  - Enhancement of cell-specific transgene expression from a Tet-Off regulatory
      system using a transcriptional amplification strategy in the rat brain.
AB  - BACKGROUND: The Tet-Off system uses a tetracycline-controlled transactivator
      protein (tTA) and a tetracycline-responsive promoter element (TRE) to regulate
      expression of a target gene. This system can be used to achieve regulatable
      transgene expression in specific cell types by employing a cell-specific promoter
      to drive tTA expression. Wide applications of this attractive approach are,
      however, hindered by relatively weak transcriptional activity of most cell
      specific promoters. We report here the feasibility of using a transcriptional
      amplification strategy to overcome the problem. METHODS AND RESULTS: In the
      developed cell-type-specific, Tet-inducible lentiviral system, two distinct
      cellular promoters were tested, a human synapsin-1 promoter for neurons and a
      compact glial fibrillary acidic protein promoter for astroglial cells. Lentiviral
      vectors were constructed that contained two copies of one or the other of these
      two promoters. One copy was used to drive the expression of a chimeric
      transactivator consisting of a part of the transcriptional activation domain of
      the NF-kappaB p65 protein fused to the DNA-binding domain of the yeast GAL4
      protein. The second copy of the cell-specific promoter was modified by
      introduction of the GAL4 binding sequences at its 5' end. This copy was used to
      drive expression of tTA. A gene encoding a red fluorescent protein was cloned
      into another lentiviral vector under transcriptional control of TRE. Co
      transduction with the two types of viral vectors provided doxycycline-regulated
      transgene expression in a neuron- or astrocyte-specific manner. Compared to
      control viruses without transcriptional amplification, our enhanced systems were
      approximately 8-fold more potent in cultured neurons and astroglial cells and at
      least 8- to 12-fold more potent in the rat brain in vivo. CONCLUSIONS: Our
      results demonstrate the effectiveness of the transcriptional amplification
      strategy in developing viral gene delivery systems that combine the advantages of
      specific cell type targeting and Tet-inducible expression.

PMID- 18324738
TI  - Pressure and temperature dependence of the chlorine NQR in caesium and sodium
      chlorates.
AB  - The (35)Cl nuclear quadrupole resonance (NQR) frequencies (nu(Q)) in caesium and
      sodium chlorates were measured as a function of temperature, from 77 to 300 K at
      different pressures up to 5.1 kbar, and the data were analysed to estimate the
      volume dependence of the electric field gradient (EFG), torsional frequency and
      also the contributions to the NQR frequency from static and dynamic effects. The
      variation of spin-lattice relaxation time with pressure at different temperatures
      was studied in the case of sodium chlorate and at room temperature in case of
      caesium chlorate. The pressure dependence of the spin-lattice relaxation time
      (T(1)) suggests that the relaxation is mainly due to the torsional motions.

PMID- 18324739
TI  - Complete assignments of 1H and 13C NMR spectral data for three polyhydroxylated
      12-ursen-type triterpenoids from Dischidia esquirolii.
AB  - The complete assignments of all the (1)H and (13)C NMR signals of three
      polyhydroxylated 12-ursen-type triterpenes, 6beta,19alpha,22alpha-trihydroxyurs
      12-en-3-oxo-28-oic acid (1), 3beta,6alpha,19alpha,23-tetrahydroxyurs-12-en-28-
      oic acid (2) and 3beta,6beta,19alpha,23-tetrahydroxyurs-12-en-28-oic acid (3),
      were carried out by means of homo- and hetero-nuclear two-dimensional NMR
      experiments. Compounds 1-3 were isolated from the aerial parts of Dischidia
      esquirolii. Of them, 1 and 2 were identified as new polyhydroxylated ursolic acid
      derivatives. Compound 2 is the C-6 hydroxyl epimer of 3, which was isolated first
      from Adina rubella, and its structure is revised in this paper.

PMID- 18324740
TI  - NMR study of the gelation of a designed gelator.
AB  - The gelation of a designed gelator was investigated by different NMR methods,
      which showed a clear thermal hysteresis. Two very simple approaches for the NMR
      determination of the gelation point are suggested. One involves the observation
      of the NMR integral, and the other records the ratio of the diffusion
      coefficients between the gelator and the solvent. Differential behavior of the
      gelator protons are interpreted as a hint that a part of the gelator molecule
      might still be flexible as in the dissolved state.

PMID- 18324741
TI  - Stacking interaction study of trans-resveratrol (trans-3,5,4'-trihydroxystilbene)
      in solution by Nuclear Magnetic Resonance and Fourier Transform Infrared
      Spectroscopy.
AB  - Interactions between aromatic rings or other unsaturated systems, including pi
      stacking and face-to-edge complexes, are the origin of many phenomena in both
      organic and biological chemistry. It is well known that these interactions play
      an important role in the stabilization of the stereo-structure of DNA and the
      tertiary structure of many proteins.Trans-resveratrol (trans-3,5,4'
      trihydroxystilbene, trans-RSV) is a phytoalexin found in Vitis sp. and in many
      other plants and food products and has received much attention because of its
      possible positive health benefits. In this work, the pi-stacking interaction of
      trans-RSV was studied by nuclear magnetic resonance (NMR) and Fourier transform
      infrared (FTIR) spectroscopy. In particular, the proton chemical shift dependence
      of the RSV concentration in the range 2 x 10(-2) - 1 x 10(-5) M and temperature
      were analysed. Moreover, the dynamics of the supramolecular aggregates were
      studied by nuclear spin relaxation data.

PMID- 18324742
TI  - Two plus two does not equal three: statistical tests for multiple genome
      comparison.
AB  - Gene clusters that span three or more chromosomal regions are of increasing
      importance, yet statistical tests to validate such clusters are in their infancy.
      Current approaches either conduct several pairwise comparisons or consider only
      the number of genes that occur in all of the regions. In this paper, we provide
      statistical tests for clusters spanning exactly three regions based on genome
      models of typical comparative genomics problems, including analysis of conserved
      linkage within multiple species and identification of large-scale duplications.
      Our tests are the first to combine evidence from genes shared among all three
      regions and genes shared between pairs of regions. We show that our tests of
      clusters spanning three regions are more sensitive than existing approaches, and
      can thus be used to identify more diverged homologous regions.

PMID- 18324743
TI  - The distribution of distances between randomly constructed genomes: generating
      function, expectation, variance and limits.
AB  - Based on a large repertoire of chromosomal rearrangement operations, the genomic
      distance d between two genomes with chi(r) and chi(b) linear chromosomes,
      respectively, both containing the same (or orthologous) n genes or markers, is
      d=n + max(chi(r),chi(b))-c, where c is the number of cycles in the breakpoint
      graph of the two genomes. In this paper, we study the exact probability
      distribution of c. We derive the expectation and variance, and show that, in the
      limit, the expectation of d is n - (2chirchib)/(2chir+2chib(-1)) - 1/2ln (n +
      max(chir,chib))/(chir+chib).

PMID- 18324744
TI  - Computing the all-pairs quartet distance on a set of evolutionary trees.
AB  - We present two algorithms for calculating the quartet distance between all pairs
      of trees in a set of binary evolutionary trees on a common set of species. The
      algorithms exploit common substructure among the trees to speed up the pairwise
      distance calculations, thus performing significantly better on large sets of
      trees compared to performing distinct pairwise distance calculations, as we
      illustrate experimentally, where we see a speedup factor of around 130 in the
      best case.

PMID- 18324745
TI  - Protein structure-structure alignment with discrete Frechet distance.
AB  - Matching two geometric objects in two-dimensional (2D) and three-dimensional (3D)
      spaces is a central problem in computer vision, pattern recognition, and protein
      structure prediction. In particular, the problem of aligning two polygonal chains
      under translation and rotation to minimize their distance has been studied using
      various distance measures. It is well known that the Hausdorff distance is useful
      for matching two point sets, and that the Frechet distance is a superior measure
      for matching two polygonal chains. The discrete Frechet distance closely
      approximates the (continuous) Frechet distance, and is a natural measure for the
      geometric similarity of the folded 3D structures of biomolecules such as
      proteins. In this paper, we present new algorithms for matching two polygonal
      chains in two dimensions to minimize their discrete Frechet distance under
      translation and rotation, and an effective heuristic for matching two polygonal
      chains in three dimensions. We also describe our empirical results on the
      application of the discrete Frechet distance to protein structure-structure
      alignment.

PMID- 18324746
TI  - Using formal concept analysis for microarray data comparison.
AB  - Microarray technologies, which can measure tens of thousands of gene expression
      values simultaneously in a single experiment, have become a common research
      method for biomedical researchers. Computational tools to analyze microarray data
      for biological discovery are needed. In this paper, we investigate the
      feasibility of using formal concept analysis (FCA) as a tool for microarray data
      analysis. The method of FCA builds a (concept) lattice from the experimental data
      together with additional biological information. For microarray data, each vertex
      of the lattice corresponds to a subset of genes that are grouped together
      according to their expression values and some biological information related to
      gene function. The lattice structure of these gene sets might reflect biological
      relationships in the dataset. Similarities and differences between experiments
      can then be investigated by comparing their corresponding lattices according to
      various graph measures. We apply our method to microarray data derived from
      influenza-infected mouse lung tissue and healthy controls. Our preliminary
      results show the promise of our method as a tool for microarray data analysis.

PMID- 18324747
TI  - Complexities and algorithms for glycan sequencing using tandem mass spectrometry.
AB  - Determining glycan structures is vital to comprehend cell-matrix, cell-cell, and
      even intracellular biological events. Glycan sequencing, which determines the
      primary structure of a glycan using tandem mass spectrometry (MS/MS), remains one
      of the most important tasks in proteomics. Analogous to peptide de novo
      sequencing, glycan de novo sequencing determines the structure without the aid of
      a known glycan database. We show in this paper that glycan de novo sequencing is
      NP-hard. We then provide a heuristic algorithm and develop a software program to
      solve the problem in practical cases. Experiments on real MS/MS data of
      glycopeptides demonstrate that our heuristic algorithm gives satisfactory results
      on practical data.

PMID- 18324748
TI  - Fitting protein chains to cubic lattice is NP-complete.
AB  - It is known that folding a protein chain into a cubic lattice is an NP-complete
      problem. We consider a seemingly easier problem: given a three-dimensional (3D)
      fold of a protein chain (coordinates of its C(alpha) atoms), we want to find the
      closest lattice approximation of this fold. This problem has been studied under
      names such as "lattice approximation of a protein chain", "the protein chain
      fitting problem", and "building of protein lattice models". We show that this
      problem is NP-complete for the cubic lattice with side close to 3.8 A and
      coordinate root mean square deviation.

PMID- 18324749
TI  - Design and analysis of quantitative differential proteomics investigations using
      LC-MS technology.
AB  - Liquid chromatography-mass spectrometry (LC-MS)-based proteomics is becoming an
      increasingly important tool in characterizing the abundance of proteins in
      biological samples of various types and across conditions. Effects of disease or
      drug treatments on protein abundance are of particular interest for the
      characterization of biological processes and the identification of biomarkers.
      Although state-of-the-art instrumentation is available to make high-quality
      measurements and commercially available software is available to process the
      data, the complexity of the technology and data presents challenges for
      bioinformaticians and statisticians. Here, we describe a pipeline for the
      analysis of quantitative LC-MS data. Key components of this pipeline include
      experimental design (sample pooling, blocking, and randomization) as well as
      deconvolution and alignment of mass chromatograms to generate a matrix of
      molecular abundance profiles. An important challenge in LC-MS-based quantitation
      is to be able to accurately identify and assign abundance measurements to members
      of protein families. To address this issue, we implement a novel statistical
      method for inferring the relative abundance of related members of protein
      families from tryptic peptide intensities. This pipeline has been used to analyze
      quantitative LC-MS data from multiple biomarker discovery projects. We illustrate
      our pipeline here with examples from two of these studies, and show that the
      pipeline constitutes a complete workable framework for LC-MS-based differential
      quantitation. Supplementary material is available at
      http://iec01.mie.utoronto.ca/~thodoros/Bukhman/.

PMID- 18324750
TI  - Likelihood of a particular order of genetic markers and the construction of
      genetic maps.
AB  - We model the recombination process of fungal systems via chromatid exchange in
      meiosis, which accounts for any type of bivalent configuration in a genetic
      interval in any specified order of genetic markers, for both random spore and
      tetrad data. First, a probability model framework is developed for two genes and
      then generalized for an arbitrary number of genes. Maximum likelihood estimators
      (MLEs) for both random and tetrad data are developed. It is shown that the MLE of
      recombination for tetrad data is uniformly more efficient over that from random
      spore data by a factor of at least 4 usually. The MLE for the generalized
      probability framework is computed using the expectation-maximization (EM)
      algorithm. Pearson's chi-squared statistic is computed as a measure of goodness
      of fit using a product-multinomial setup. We implement our model with genetic
      marker data on the whole genome of Neurospora crassa. Simulated annealing is used
      to search for the best order of genetic markers for each chromosome, and the
      goodness of fit value is evaluated for model assumptions. Inferred map orders are
      corroborated by genomic sequence, with the exception of linkage groups I, II, and
      V.

PMID- 18324751
TI  - TALI: local alignment of protein structures using backbone torsion angles.
AB  - Torsion angle alignment (TALI) is a novel approach to local structural motif
      alignment, based on backbone torsion angles (phi, psi) rather than the more
      traditional atomic distance matrices. Representation of a protein structure in
      the form of a sequence of torsion angles enables easy integration of sequence and
      structural information, and adopts mature techniques in sequence alignment to
      improve performance and alignment quality. We show that TALI is able to match
      local structural motifs as well as identify global structural similarity. TALI is
      also compared to other structure alignment methods such as DALI, CE, and SSM, as
      well as sequence alignment based on PSI-BLAST; TALI is shown to be equally
      successful as, or more successful than, these other methods when applied to
      challenging structural alignments. The inference of the evolutionary tree of
      class II aminoacyl-tRNA synthetase shows the potential for TALI in estimating
      protein structural evolution and in identifying structural divergence among
      homologous structures. AVAILABILITY: http://redcat.cse.sc.edu/index.php/ PROJECT:
      TALI/.

PMID- 18324752
TI  - Deriving topology and sequence alignment for the helix skeleton in low-resolution
      protein density maps.
AB  - Cryoelectron microscopy (cryoEM) is an experimental technique to determine the
      three-dimensional (3D) structure of large protein complexes. Currently, this
      technique is able to generate protein density maps at 6-9 A resolution, at which
      the skeleton of the structure (which is composed of alpha-helices and beta
      sheets) can be visualized. As a step towards predicting the entire backbone of
      the protein from the protein density map, we developed a method to predict the
      topology and sequence alignment for the skeleton helices. Our method combines the
      geometrical information of the skeleton helices with the Rosetta ab initio
      structure prediction method to derive a consensus topology and sequence alignment
      for the skeleton helices. We tested the method with 60 proteins. For 45 proteins,
      the majority of the skeleton helices were assigned a correct topology from one of
      our top ten predictions. The offsets of the alignment for most of the assigned
      helices were within +/-2 amino acids in the sequence. We also analyzed the use of
      the skeleton helices as a clustering tool for the decoy structures generated by
      Rosetta. Our comparison suggests that the topology clustering is a better method
      than a general overlap clustering method to enrich the ranking of decoys,
      particularly when the decoy pool is small.

PMID- 18324753
TI  - ClusFCM: an algorithm for predicting protein functions using homologies and
      protein interactions.
AB  - We introduce a new algorithm, called ClusFCM, which combines techniques of
      clustering and fuzzy cognitive maps (FCM) for prediction of protein functions.
      ClusFCM takes advantage of protein homologies and protein interaction network
      topology to improve low recall predictions associated with existing prediction
      methods. ClusFCM exploits the fact that proteins of known function tend to
      cluster together and deduce functions not only through their direct interaction
      with other proteins, but also from other proteins in the network. We use ClusFCM
      to annotate protein functions for Saccharomyces cerevisiae (yeast),
      Caenorhabditis elegans (worm), and Drosophila melanogaster (fly) using protein
      protein interaction data from the General Repository for Interaction Datasets
      (GRID) database and functional labels from Gene Ontology (GO) terms. The
      algorithm's performance is compared with four state-of-the-art methods for
      function prediction--Majority, chi(2) statistics, Markov random field (MRF), and
      FunctionalFlow--using measures of Matthews correlation coefficient, harmonic
      mean, and area under the receiver operating characteristic (ROC) curves. The
      results indicate that ClusFCM predicts protein functions with high recall while
      not lowering precision. Supplementary information is available at
      http://www.egr.vcu.edu/cs/dmb/ClusFCM/.

PMID- 18324754
TI  - Feature selection in validating mass spectrometry database search results.
AB  - Tandem mass spectrometry (MS/MS) combined with protein database searching has
      been widely used in protein identification. A validation procedure is generally
      required to reduce the number of false positives. Advanced tools using
      statistical and machine learning approaches may provide faster and more accurate
      validation than manual inspection and empirical filtering criteria. In this
      study, we use two feature selection algorithms based on random forest and support
      vector machine to identify peptide properties that can be used to improve
      validation models. We demonstrate that an improved model based on an optimized
      set of features reduces the number of false positives by 58% relative to the
      model which used only search engine scores, at the same sensitivity score of 0.8.
      In addition, we develop classification models based on the physicochemical
      properties and protein sequence environment of these peptides without using
      search engine scores. The performance of the best model based on the support
      vector machine algorithm is at 0.8 AUC, 0.78 accuracy, and 0.7 specificity,
      suggesting a reasonably accurate classification. The identified properties
      important to fragmentation and ionization can be either used in independent
      validation tools or incorporated into peptide sequencing and database search
      algorithms to improve existing software programs.

PMID- 18324755
TI  - A survey on haplotyping algorithms for tightly linked markers.
AB  - Two grand challenges in the postgenomic era are to develop a detailed
      understanding of heritable variation in the human genome, and to develop robust
      strategies for identifying the genetic contribution to diseases and drug
      responses. Haplotypes of single nucleotide polymorphisms (SNPs) have been
      suggested as an effective representation of human variation, and various
      haplotype-based association mapping methods for complex traits have been proposed
      in the literature. However, humans are diploid and, in practice, genotype data
      instead of haplotype data are collected directly. Therefore, efficient and
      accurate computational methods for haplotype reconstruction are needed and have
      recently been investigated intensively, especially for tightly linked markers
      such as SNPs. This paper reviews statistical and combinatorial haplotyping
      algorithms using pedigree data, unrelated individuals, or pooled samples.

PMID- 18324756
TI  - Hemozymes peroxidase activity of artificial hemoproteins constructed from the
      Streptomyces lividans xylanase A and iron(III)-carboxy-substituted porphyrins.
AB  - To develop artificial hemoproteins that could lead to new selective oxidation
      biocatalysts, a strategy based on the insertion of various iron-porphyrin
      cofactors into Xylanase A (Xln10A) was chosen. This protein has a globally
      positive charge and a wide enough active site to accommodate metalloporphyrins
      that possess negatively charged substituents such as microperoxidase 8 (MP8),
      iron(III)-tetra-alpha4-ortho-carboxyphenylporphyrin (Fe(ToCPP)), and iron(III)
      tetra-para-carboxyphenylporphyrin (Fe(TpCPP)). Coordination chemistry of the iron
      atom and molecular modeling studies showed that only Fe(TpCPP) was able to insert
      deeply into Xln10A, with a KD value of about 0.5 microM. Accordingly, Fe(TpCPP)
      Xln10A bound only one imidazole molecule, whereas Fe(TpCPP) free in solution was
      able to bind two, and the UV-visible spectrum of the Fe(TpCPP)-Xln10A-imidazole
      complex suggested the binding of an amino acid of the protein on the iron atom,
      trans to the imidazole. Fe(TpCPP)-Xln10A was found to have peroxidase activity,
      as it was able to catalyze the oxidation of typical peroxidase cosubstrates such
      as guaiacol and o-dianisidine by H2O2. With these two cosubstrates, the KM value
      measured with the Fe(TpCPP)-Xln10A complex was higher than those values observed
      with free Fe(TpCPP), probably because of the steric hindrance and the increased
      hydrophobicity caused by the protein around the iron atom of the porphyrin. The
      peroxidase activity was inhibited by imidazole, and a study of the pH dependence
      of the oxidation of o-dianisidine suggested that an amino acid with a pKA of
      around 7.5 was participating in the catalysis. Finally, a very interesting
      protective effect against oxidative degradation of the porphyrin was provided by
      the protein.

PMID- 18324757
TI  - First CoMFA characterization of vesamicol analogs as ligands for the vesicular
      acetylcholine transporter.
AB  - Vesamicol derivatives are promising candidates as ligands for the vesicular
      acetylcholine transporter (VAChT) to enable in vivo imaging of cholinergic
      deficiencies if applied as positron emission tomography radiotracers. So far,
      optimization of the binding affinity of vesamicol-type ligands was hampered by
      the lack of respective quantitative structure-activity relationships. We
      developed the first quantitative model to predict, from molecular structure, the
      binding affinity of vesamicol-type ligands toward VAChT employing comparative
      molecular field analysis (CoMFA) for a set of 37 ligands, covering three
      different structural types (4-phenylpiperidine, spiro, and tropan derivatives of
      vesamicol). The prediction capability was assessed by leave-one-out cross
      validation (LOO) and through leaving out and predicting 50% of the compounds
      selected such that both the training and the prediction sets cover almost the
      whole range of experimental data. The statistics indicate a significant
      prediction power of the models ( q (2) (LOO) = 0.66, q (2) (50% out) = 0.59
      0.74). The discussion includes detailed analyses of CoMFA regions critical for
      ligand-VAChT binding, identifying structural implications for high binding
      affinity.

PMID- 18324758
TI  - Combination of virtual screening and high throughput gene profiling for
      identification of novel liver X receptor modulators.
AB  - We conducted virtual docking studies using GLIDE with modified LXRbeta ligand
      binding domain (LBD) on internal compound collection followed by the gene
      profiling with ArrayPlate mRNA assay. A total of 69 compounds were found to
      upregulate LXRalpha and certain LXR regulated genes from 1308 compounds selected
      by virtual screen (hit rate: 5.3%). Compound 4 was shown to significantly induce
      the expression of LXR target genes such as ABCA1, ABCG1, APOE, SCD-1, and SREBP
      1c in THP-1 differentiated macrophages. In vitro binding assay confirmed that 4
      binds to both LXRalpha and LXRbeta directly and recruits coactivator peptide SRC
      1. It functions as a full LXR agonist in stimulating cholesterol efflux in THP-1
      differentiated macrophages and induces lipogenesis in HepG2 cells. This study
      demonstrates that the combination of virtual screen and high throughput gene
      profiling is an efficient approach for rapid identification of novel LXR
      modulators.

PMID- 18324759
TI  - Evaluation of a series of naphthamides as potent, orally active vascular
      endothelial growth factor receptor-2 tyrosine kinase inhibitors.
AB  - We have previously shown N-arylnaphthamides can be potent inhibitors of vascular
      endothelial growth factor receptors (VEGFRs). N-Alkyl and N-unsubstituted
      naphthamides were prepared and found to yield nanomolar inhibitors of VEGFR-2
      (KDR) with an improved selectivity profile against a panel of tyrosine and
      serine/threonine kinases. The inhibitory activity of this series was retained at
      the cellular level. Naphthamides 3, 20, and 22 exhibited good pharmacokinetics
      following oral dosing and showed potent inhibition of VEGF-induced angiogenesis
      in the rat corneal model. Once-daily oral administration of 22 for 14 days led to
      85% inhibition of established HT29 colon cancer and Calu-6 lung cancer xenografts
      at doses of 10 and 20 mg/kg, respectively.

PMID- 18324760
TI  - Development of potent and selective phosphinic peptide inhibitors of angiotensin
      converting enzyme 2.
AB  - Angiotensin-converting enzyme 2 (ACE2), a recently identified human homologue of
      angiotensin-converting enzyme, is a zinc metallocarboxypeptidase which may play a
      unique role in cardiovascular and renal function. Here we report the discovery of
      potent and selective inhibitors of ACE2, which have been identified by evaluating
      a series of phosphinic di- and tripeptides of the general formula: Z-Xaa(PO 2-CH
      2)YaaOH and Ac-Zaa-Xaa(PO 2-CH 2)YaaOH. The most potent inhibitor in this series
      is a tripeptide that displays a K i value of 0.4 nM toward ACE2 and is 3 orders
      of magnitude less potent toward carboxypeptidase A. Phosphinic tripeptides
      exhibit high potency exclusively when the Xaa position is occupied by a
      pseudoproline. A model of interaction between one inhibitor of this series and
      ACE2 suggests that the critical role played by a proline in inhibitors, but also
      for substrates hydrolysis, may rely on the presence of Tyr (510) in the ACE2
      active site.

PMID- 18324761
TI  - Naphthamides as novel and potent vascular endothelial growth factor receptor
      tyrosine kinase inhibitors: design, synthesis, and evaluation.
AB  - A series of naphthyl-based compounds were synthesized as potential inhibitors of
      vascular endothelial growth factor (VEGF) receptors. Investigations of structure
      activity relationships led to the identification of a series of naphthamides that
      are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous
      analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical
      vein endothelial cell (HUVEC) proliferation, and of these several compounds
      possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48
      demonstrated significant antitumor efficacy against established HT29 human colon
      adenocarcinoma xenografts implanted in athymic mice. A full account of the
      preparation, structure-activity relationships, pharmacokinetic properties, and
      pharmacology of analogues within this series is presented.

PMID- 18324762
TI  - Design, synthesis, and biological evaluation of (hydroxyphenyl)naphthalene and 
      quinoline derivatives: potent and selective nonsteroidal inhibitors of 17beta
      hydroxysteroid dehydrogenase type 1 (17beta-HSD1) for the treatment of estrogen
      dependent diseases.
AB  - Human 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyzes the
      reduction of the weak estrogen estrone (E1) to the highly potent estradiol (E2).
      This reaction takes place in the target cell where the estrogenic effect is
      exerted via the estrogen receptor (ER). Estrogens, especially E2, are known to
      stimulate the proliferation of hormone-dependent diseases. 17beta-HSD1 is
      overexpressed in many breast tumors. Thus, it is an attractive target for the
      treatment of these diseases. Ligand- and structure-based drug design led to the
      discovery of novel, selective, and potent inhibitors of 17beta-HSD1. Phenyl
      substituted bicyclic moieties were synthesized as mimics of the steroidal
      substrate. Computational methods were used to obtain insight into their
      interactions with the protein. Compound 5 turned out to be a highly potent
      inhibitor of 17beta-HSD1 showing good selectivity (17beta-HSD2, ERalpha and
      beta), medium cell permeation, reasonable metabolic stability (rat hepatic
      microsomes), and little inhibition of hepatic CYP enzymes.

PMID- 18324763
TI  - Synthesis and biological activity of a 3,4,5-trimethoxybenzoyl ester analogue of
      epicatechin-3-gallate.
AB  - Despite presenting bioavailability problems, tea catechins have emerged as
      promising chemopreventive agents because of their observed efficacy in various
      animal models. To improve the stability and cellular absorption of tea
      polyphenols, we developed a new catechin-derived compound, 3- O-(3,4,5
      trimethoxybenzoyl)-(-)-epicatechin (TMECG), which has shown significant
      antiproliferative activity against several cancer cell lines, especially
      melanoma. The presence of methoxy groups in its ester-bound gallyl moiety
      drastically decreased its antioxidant and prooxidant properties without affecting
      its cell-antiproliferative effects, and the data indicated that the 3-gallyl
      moiety was essential for its biological activity. As regards its action
      mechanism, we demonstrated that TMECG binds efficiently to human dihydrofolate
      reductase and down-regulates folate cycle gene expression in melanoma cells.
      Disruption of the folate cycle by TMECG is a plausible explanation for its
      observed biological effects and suggests that, like other antifolate compounds,
      TMECG could be of clinical value in cancer therapy.

PMID- 18324764
TI  - Pharmacophore modeling, quantitative structure-activity relationship analysis,
      and in silico screening reveal potent glycogen synthase kinase-3beta inhibitory
      activities for cimetidine, hydroxychloroquine, and gemifloxacin.
AB  - The pharmacophoric space of glycogen synthase kinase-3beta (GSK-3beta) was
      explored using two diverse sets of inhibitors. Subsequently, genetic algorithm
      and multiple linear regression analysis were employed to select optimal
      combination of pharmacophores and physicochemical descriptors that access self
      consistent and predictive quantitative structure-activity relationship (QSAR)
      against 132 training compounds ( r (2) 123 = 0.663, F = 24.6, r (2) LOO = 0.592,
      r (2) PRESS against 29 external test inhibitors = 0.695). Two orthogonal
      pharmacophores emerged in the QSAR, suggesting the existence of at least two
      distinct binding modes accessible to ligands within GSK-3beta binding pocket. The
      validity of the QSAR equation and the associated pharmacophores was established
      by the identification of three nanomolar GSK-3beta inhibitors retrieved from our
      in-house-built structural database of established drugs, namely,
      hydroxychloroquine, cimetidine, and gemifloxacin. Docking studies supported the
      binding modes suggested by the pharmacophore/QSAR analysis. In addition to being
      excellent leads for subsequent optimization, the anti-GSK-3beta activities of
      these drugs should have significant clinical implications.

PMID- 18324765
TI  - A hybrid method for peptide identification using integer linear optimization,
      local database search, and quadrupole time-of-flight or OrbiTrap tandem mass
      spectrometry.
AB  - A novel hybrid methodology for the automated identification of peptides via de
      novo integer linear optimization, local database search, and tandem mass
      spectrometry is presented in this article. A modified version of the de novo
      identification algorithm PILOT, is utilized to construct accurate de novo peptide
      sequences. A modified version of the local database search tool FASTA is used to
      query these de novo predictions against the nonredundant protein database to
      resolve any low-confidence amino acids in the candidate sequences. The
      computational burden associated with performing several alignments is alleviated
      with the use of distributive computing. Extensive computational studies are
      presented for this new hybrid methodology, as well as comparisons with MASCOT for
      a set of 38 quadrupole time-of-flight (QTOF) and 380 OrbiTrap tandem mass
      spectra. The results for our proposed hybrid method for the OrbiTrap spectra are
      also compared with a modified version of PepNovo, which was trained for use on
      high-precision tandem mass spectra, and the tag-based method InsPecT. The de novo
      sequences of PILOT and PepNovo are also searched against the nonredundant protein
      database using CIDentify to compare with the alignments achieved by our
      modifications of FASTA. The comparative studies demonstrate the excellent peptide
      identification accuracy gained from combining the strengths of our de novo
      method, which is based on integer linear optimization, and database driven search
      methods.

PMID- 18324766
TI  - Proteomic analysis of microsomes from lactating bovine mammary gland.
AB  - Mammary gland has multiple metabolic potential including for large-scale
      synthesis of milk proteins, carbohydrate, and lipids including nutrient
      triacylglycerols. We have carried out a proteomic analysis of mammary tissue to
      discover proteins that affect lipid metabolism. Unfractionated microsomes from
      lactating bovine mammary tissue were analyzed using one-dimensional SDS-PAGE with
      RPLC-ESI-MS/MS. This approach gave 703 proteins including 160 predicted
      transmembrane proteins. Proteins were classified according to their subcellular
      localizations and biological functions. Over 50 proteins were associated with
      cellular uptake, metabolism, and secretion of lipids, including some enzymes that
      have been previously associated with breast cancer and potential therapeutic
      targets. This database develops a proteomic view of the metabolic potential of
      mammary gland that can be expected to contribute to a greater understanding of
      gene expression and tissue remodeling associated with lactation, and to further
      dissection of normal and pathological processes in mammary tissue.

PMID- 18324767
TI  - Effect of structural dynamics on charge transfer in DNA hairpins.
AB  - We present a theoretical study of the positive charge transfer in stilbene-linked
      DNA hairpins containing only AT base pairs using a tight-binding model that
      includes a description of structural fluctuations. The parameters are the charge
      transfer integral between neighboring units and the site energies. Fluctuations
      in these parameters were studied by a combination of molecular dynamics
      simulations of the structural dynamics and density functional theory calculations
      of charge transfer integrals and orbital energies. The fluctuations in both
      parameters were found to be substantial and to occur on subpicosecond time
      scales. Tight-binding calculations of the dynamics of charge transfer show that
      for short DNA hairpins (<4 base pairs) the charge moves by a single-step
      superexchange mechanism with a relatively strong distance dependence. For longer
      hairpins, a crossover to a fluctuation-assisted incoherent mechanism was found.
      Analysis of the charge distribution during the charge transfer process indicates
      that for longer bridges substantial charge density builds up on the bridge, but
      this charge density is mostly confined to the adenine next to the hole donor.
      This is caused by the electrostatic interaction between the hole on the AT bridge
      and the negative charge on the hole donor. We conclude both that the relatively
      strong distance dependence for short bridges is mostly due to this electrostatic
      interaction and that structural fluctuations play a critical role in the charge
      transfer, especially for longer bridge lengths.

PMID- 18324768
TI  - Self-assembly, molecular dynamics, and kinetics of structure formation in dipole
      functionalized discotic liquid crystals.
AB  - The self-assembly, the molecular dynamics, and the kinetics of structure
      formation are studied in dipole-functionalized hexabenzocoronene (HBC)
      derivatives. Dipole substitution destabilizes the columnar crystalline phase
      except for the dimethoxy- and monoethynyl-substituted HBCs that undergo a
      reversible transformation to the crystalline phase. The disk dynamics are studied
      by dielectric spectroscopy and site-specific NMR techniques that provide both the
      time-scale and geometry of motion. Application of pressure results in the
      thermodynamic phase diagram that shows increasing stability of the crystalline
      phase at elevated pressures. Long-lived metastability was found during the
      transformation between the two phases. These results suggest new thermodynamic
      and kinetic pathways that favor the phase with the highest charge carrier
      mobility.

PMID- 18324769
TI  - Cancer risk to Japanese population from the consumption of inorganic arsenic in
      cooked hijiki.
AB  - The cancer risk posed by inorganic arsenic (iAs) ingestion via the consumption of
      hijiki seaweed, a common Japanese food item known to accumulate pentavalent
      arsenic, was estimated. Fourteen households were asked to supply three portions
      of cooked hijiki (boiled and fried with vegetables and fried bean curd, etc.), as
      usually cooked and served per person in each household. The monthly consumption
      frequency of cooked hijiki was assessed by questionnaire: it was typically two to
      three times a month in most households. The mean daily consumption of cooked
      hijiki was estimated to be 6.5 g/day (range = 1.1-14 g/day, median = 5.5 g/day)
      by multiplying one serving quantity (grams) by the monthly frequency of
      consumption. The concentration of iAs [As(III) + As(V)] in the cooked hijiki was
      determined after homogenization, freeze-drying, 0.07 mol/L HCl extraction, and
      high-performance liquid chromatography-inductively coupled plasma mass
      spectrometry (HPLC-ICPMS). The concentration of iAs ranged from 0.4 to 2.8 mg/kg
      (wet weight basis) in the cooked hijiki, and iAs intake from cooked hijiki was
      calculated to be 0.0005-0.023 mg/day. On the basis of these data and the oral
      slope factor [1.5E0 (mg/kg/day) (-1)] reported by the U.S. EPA for iAs, the mean
      skin cancer risk through cooked hijiki consumption was calculated to be 2.4 x 10(
      4) (range = 1.6 x 10(-6) -7.0 x 10(-4)), which exceeded the acceptable level of
      10(-5). Taking the risk of other cancers (bladder, lung, etc.) into
      consideration, the contribution to cancer occurrence through the consumption of
      hijiki seaweed may not be negligible.

PMID- 18324770
TI  - Alginate and chitosan functionalization for micronutrient encapsulation.
AB  - A new method for encapsulation of micronutrients was successfully developed. The
      encapsulation matrix consisted of two polymers (alginate and chitosan), which
      were functionalized by acylation with palmitoyl chloride. The structural
      modifications of polymers were confirmed by Fourier transform infrared (FTIR)
      spectroscopy. Beads were formed by ionic gelation, and their mechanical and
      physical characteristics (puncture strength and deformation, viscoelasticity,
      water vapor permeability, and rate of gel swelling) were evaluated using beads or
      films made of bead-forming solutions. Functionalization increased elasticity and
      water impermeability of polymer films. Stability of selected encapsulated
      micronutrients (ferrous fumarate, ascorbic acid, and beta-carotene) was also
      evaluated under two levels of temperature (23 and 45 degrees C) and relative
      humidity (56 and 100%) for 6 months. Encapsulation strongly increased the
      stability of micronutrients. No difference was observed in the encapsulated
      micronutrients' stability between nonfunctionalized and functionalized beads.
      Finally, a release study in gastrointestinal media was conducted. Results showed
      that beads were not susceptible to enzymatic and acidic attacks during stomach
      transit. This research demonstrates the potential of a new encapsulation method
      to protect bioactive molecules from temperature, moisture, and acidic conditions.

PMID- 18324771
TI  - Character impact odorants of high-heat skim milk powder isolated by simultaneous
      distillation-extraction.
AB  - To identify the character impact odorant of high-heat skim milk powder (HHSMP), a
      comparative study using ultrahigh-temperature (UHT) milk was performed. Aroma
      concentrate was prepared by column adsorption combined with simultaneous
      distillation-extraction. Aroma extract dilution analysis (AEDA) revealed 58 aroma
      peaks with flavor dilution (FD) factors ranging from 10 to 3000; from these, 41
      compounds were identified and 7 compounds were tentatively identified (FD factor
      > or = 300). Among these HHSMP and UHT milk components, methyl 2-methyl-3-furyl
      disulfide and bis(2-methyl-3-furyl) disulfide, which appeared to be generated
      during the processing of each product, were identified. When the results of the
      AEDA of both samples were compared, it was considered that the characteristic
      aroma of HHSMP was not explained by a single compound but instead formed from a
      mixture of several types of compounds contained in common with the UHT milk. The
      contribution of these compounds to the aroma of HHSMP was confirmed by an aroma
      simulation experiment.

PMID- 18324772
TI  - Dietary phosphatidylinositol prevents the development of nonalcoholic fatty liver
      disease in Zucker (fa/fa) rats.
AB  - Recent studies have shown that dietary phospholipids, especially
      phosphatidylcholine and phosphatidylserine, have various beneficial biological
      effects. However, there are not enough data concerning the physiological function
      of dietary phosphatidylinositol (PI). The metabolic syndrome, a cluster of
      metabolic abnormalities such as dyslipidemia, diabetes mellitus, and
      hypertension, is a widespread and increasingly prevalent disease in
      industrialized countries. Nonalcoholic fatty liver disease (NAFLD) is often
      associated with features of the metabolic syndrome. NAFLD describes the spectrum
      of liver damage ranging from hepatic steatosis to steatohepatitis, liver
      fibrosis, and cirrhosis, and it is emerging as the most common liver disease
      worldwide. The present study examined whether dietary PI protects Zucker ( fa/
      fa) rats from the metabolic syndrome. For 4 weeks, rats were fed semisynthetic
      diets containing either 7% soybean oil or 5% soybean oil plus 2% PI. Dietary PI
      markedly prevented the development of hepatomegaly and hepatic steatosis and
      lowered hepatic injury markers in serum. Additionally, hyperinsulinemia was
      relieved by the feeding of dietary PI in Zucker rats. These effects were
      attributable to an increase in serum adiponectin, enhancement of fatty acid beta
      oxidation, and suppression of mRNA expression of inflammatory genes in the liver.
      This is the first report that dietary PI increases serum adiponectin level and
      prevents the development of NAFLD in a rat model of the metabolic syndrome.

PMID- 18324773
TI  - Liquid-liquid extraction for the enrichment of edible oils with phenols from
      olive leaf extracts.
AB  - A liquid-liquid extraction method to enrich edible oils--olive, sunflower, and
      soy oils--with phenols from olive leaf extracts is proposed. After microwave
      assistance to remove the phenols from three varieties of olive leaves,
      concentrations in the extracts between 12921 and 5173 mg/L of oleuropein, between
      488 and 192 mg/L of apigenin-7-glucoside, between 444 and 219 mg/L of luteolin-7
      glucoside, and between 501 and 213 mg/L of verbascoside were obtained, which
      clearly depended on the target variety. After optimization of the liquid-liquid
      extraction step, the concentrations in oils were 442, 162, and 164 mg/L of
      oleuropein, respectively, which were also enriched in apigenin-7-glucoside
      (between 8 and 15 mg/L, depending of the oil), lutelin-7-glucoside (between 11
      and 12 mg/L), and verbascoside (between 11 and 13 mg/L). The oil-extract
      distribution factor of these compounds was also calculated for all olive leaf
      varieties and edible oils using different extracts concentrations and also
      different oil-extract volume ratios. Thus, a door is open to enrichment of any
      oil with olive phenols at preset concentrations using extracts preconcentrated as
      required and taking into account the distribution factor of the target compounds
      between the oil and the extracts.

PMID- 18324774
TI  - Wetting the (110) and (100) surfaces of Ibeta cellulose studied by molecular
      dynamics.

PMID- 18324775
TI  - Protein-reactive, thermoresponsive copolymers with high flexibility and
      biodegradability.
AB  - A family of injectable, biodegradable, and thermosensitive copolymers based on N
      isopropylacrylamide, acrylic acid, N-acryloxysuccinimide, and a macromer
      polylactide-hydroxyethyl methacrylate were synthesized by free radical
      polymerization. Copolymers were injectable at or below room temperature and
      formed robust hydrogels at 37 degrees C. The effects of monomer ratio,
      polylactide length, and AAc content on the chemical and physical properties of
      the hydrogel were investigated. Copolymers exhibited lower critical solution
      temperatures (LCSTs) from 18 to 26 degrees C. After complete hydrolysis,
      hydrogels were soluble in phosphate buffered saline at 37 degrees C with LCSTs
      above 40.8 degrees C. Incorporation of type I collagen at varying mass fractions
      by covalent reaction with the copolymer backbone slightly increased LCSTs. Water
      content was 32-80% without collagen and increased to 230% with collagen at 37
      degrees C. Hydrogels were highly flexible and relatively strong at 37 degrees C,
      with tensile strengths from 0.3 to 1.1 MPa and elongations at break from 344 to
      1841% depending on NIPAAm/HEMAPLA ratio, AAc content, and polylactide length.
      Increasing the collagen content decreased both elongation at break and tensile
      strength. Hydrogel weight loss at 37 degrees C was 85-96% over 21 days and varied
      with polylactide content. Hydrogel weight loss at 37 degrees C was 85-96% over 21
      days and varied with polylactide content. Degradation products were shown to be
      noncytotoxic. Cell adhesion on the hydrogels was 30% of that for tissue culture
      polystyrene but increased to statistically approximate this control surface after
      collagen incorporation. These newly described thermoresponsive copolymers
      demonstrated attractive properties to serve as cell or pharmaceutical delivery
      vehicles for a variety of tissue engineering applications.

PMID- 18324777
TI  - Solution properties of conventional gum arabic and a matured gum arabic (Acacia
      (sen) SUPER GUM).
AB  - Dilute solution properties of two specially matured gum arabic samples (EM1 and
      EM2) were compared to the conventional gum (EM0) using static light scattering.
      The apparent molar mass (M(w,app) and radius of gyration (R(g,app)) for the three
      samples showed unusual concentration dependence. These data were satisfactorily
      interpreted by a simple association model that takes into account the repulsive
      interaction among clusters, which allowed us to obtain the true molar mass
      (Mw(0)) and radius of gyration (Rg(0)). A common power law relation was observed
      between Mw(0) and Rg(0) , giving a somewhat higher exponent than expected for
      linear and branched polymers in a good solvent. Mw(0) and Rg(0) obtained for the
      three gums do not differ significantly from each other. However, the data showed
      clearly a constant increase of the association from EM0 to EM2 with increasing
      concentration. This is in accordance with the previously observed improved
      functional properties for the matured products.

PMID- 18324776
TI  - Hydrolytically degradable hyaluronic acid hydrogels with controlled temporal
      structures.
AB  - Polysaccharides are being processed into biomaterials for numerous biological
      applications due to their native source in numerous tissues and biological
      functions. For instance, hyaluronic acid (HA) is found abundantly in the body,
      interacts with cells through surface receptors, and can regulate cellular
      behavior (e.g., proliferation, migration). HA was previously modified with
      reactive groups to form hydrogels that are degraded by hyaluronidases, either
      added exogenously or produced by cells. However, these hydrogels may be
      inhibitory and their applications are limited if the appropriate enzymes are not
      present. Here, for the first time, we synthesized HA macromers and hydrogels that
      are both hydrolytically (via ester group hydrolysis) and enzymatically
      degradable. The hydrogel degradation and growth factor release was tailored
      through the hydrogel cross-linking density (i.e., macromer concentration) and
      copolymerization with purely enzymatically degradable macromers. When mesenchymal
      stem cells (MSCs) were encapsulated in the hydrogels, cellular organization and
      tissue distribution was influenced by the copolymer concentration. Importantly,
      the distribution of released extracellular matrix molecules (e.g., chondroitin
      sulfate) was improved with increasing amounts of the hydrolytically degradable
      component. Overall, this new macromer allows for enhanced control over the
      structural evolution of the HA hydrogels toward applications as biomaterials.

PMID- 18324778
TI  - Hydrolysis of the amorphous cellulose in cotton-based paper.
AB  - Hydrolysis of cellulose in Whatman no. 42 cotton-based paper was studied using
      gel permeation chromatography (GPC), electrospray ionization-mass spectrometry
      (ESI-MS), and uniaxial tensile testing to understand the course and kinetics of
      the reaction. GPC results suggested that scission reactions passed through three
      stages. Additionally, the evolution of soluble oligomers in the ESI-MS data and
      the steady course of strength loss showed that the hydrolysis reaction occurred
      at a constant rate. These findings are explained with a more detailed description
      of the cellulose hydrolysis, which includes multiple chain scissions on amorphous
      segments. The breaks occur with increasing frequency near the ends of amorphous
      segments, where chains protrude from crystalline domains. Oligomers unattached to
      crystalline domains are eventually created. Late-stage reactions near the ends of
      amorphous segments produce a kinetic behavior that falsely suggests that
      hydrolysis had ceased. Monte Carlo simulations of cellulose degradation
      corroborated the experimental findings.

PMID- 18324779
TI  - Changes at the KinA PAS-A dimerization interface influence histidine kinase
      function.
AB  - The Bacillus subtilis KinA protein is a histidine protein kinase that controls
      the commitment of this organism to sporulate in response to nutrient deprivation
      and several other conditions. Prior studies indicated that the N-terminal Per
      ARNT-Sim domain (PAS-A) plays a critical role in the catalytic activity of this
      enzyme, as demonstrated by the significant decrease of the autophosphorylation
      rate of a KinA protein lacking this domain. On the basis of the environmental
      sensing role played by PAS domains in a wide range of proteins, including other
      bacterial sensor kinases, it has been suggested that the PAS-A domain plays an
      important regulatory role in KinA function. We have investigated this potential
      by using a combination of biophysical and biochemical methods to examine PAS-A
      structure and function, both in isolation and within the intact protein. Here, we
      present the X-ray crystal structure of the KinA PAS-A domain, showing that it
      crystallizes as a homodimer using beta-sheet/beta-sheet packing interactions as
      observed for several other PAS domain complexes. Notably, we observed two dimers
      with tertiary and quaternary structure differences in the crystalline lattice,
      indicating significant structural flexibility in these domains. To confirm that
      KinA PAS-A also forms dimers in solution, we used a combination of NMR
      spectroscopy, gel filtration chromatography, and analytical ultracentrifugation,
      the results of which are all consistent with the crystallographic results. We
      experimentally tested the importance of several residues at the dimer interface
      using site-directed mutagenesis, finding changes in the PAS-A domain that
      significantly alter KinA enzymatic activity in vitro and in vivo. These results
      support the importance of PAS domains within KinA and other histidine kinases and
      suggest possible routes for natural or artificial regulation of kinase activity.

PMID- 18324780
TI  - Biochemical basis for the functional switch that regulates hepatocyte growth
      factor receptor tyrosine kinase activation.
AB  - Ligand-induced dimerization of receptor tyrosine kinases (RTKs) modulates a
      system of linked biochemical reactions, sharply switching the RTK from a
      quiescent state to an active state that becomes phosphorylated and triggers
      intracellular signaling pathways. To improve our understanding of this molecular
      switch, we developed a quantitative model for hepatocyte growth factor receptor
      (c-MET) activation using parameters derived in large part from c-MET kinetic and
      thermodynamic experiments. Our model accurately produces the qualitative and
      quantitative dynamic features of c-MET phosphorylation observed in cells
      following ligand binding, including a rapid transient buildup of phosphorylated c
      MET at high ligand concentrations. In addition, our model predicts a slow buildup
      of phosphorylated c-MET under conditions of reduced phosphatase activity and no
      extracellular agonist. Significantly, this predicted response is observed in
      cells treated with phosphatase inhibitors, further validating our model.
      Parameter sensitivity studies clearly show that synergistic oligomerization
      dependent changes in c-MET kinetic, thermodynamic, and dephosphorylation
      properties result in the selective activation of the dimeric receptor, confirming
      that this model can be used to accurately evaluate the relative importance of
      linked biochemical reactions important for c-MET activation. Our model suggests
      that the functional differences observed between c-MET monomers and dimers may
      have incrementally evolved to optimize cell surface signaling responses.

PMID- 18324781
TI  - Activation of SAD kinase by Ca2+/calmodulin-dependent protein kinase kinase.
AB  - To search for the downstream target protein kinases of Ca (2+)/calmodulin
      dependent protein kinase kinase (CaMKK), we performed affinity chromatography
      purification of a rat brain extract using a GST-fused CaMKKalpha catalytic domain
      (residues 126-434) as the affinity ligand. Proteomic analysis was then carried
      out to identify the CaMKK-interacting protein kinases. In addition to identifying
      the catalytic subunit of 5'-AMP-activated protein kinase, we identified SAD-B as
      interacting. A phosphorylation assay and mass spectrometry analysis revealed that
      SAD-B was phosphorylated in vitro by CaMKK at Thr (189) in the activation loop.
      Phosphorylation of Thr (189) by CaMKKalpha induced SAD-B kinase activity by over
      60-fold. In transfected COS-7 cells, kinase activity and Thr (189)
      phosphorylation of overexpressed SAD-B were significantly enhanced by
      coexpression of constitutively active CaMKKalpha (residues 1-434) in a manner
      similar to that observed with coexpression of LKB1, STRAD, and MO25. Taken
      together, these results indicate that CaMKKalpha is capable of activating SAD-B
      through phosphorylation of Thr (189) both in vitro and in vivo and demonstrate
      for the first time that CaMKK may be an alternative activating kinase for SAD-B.

PMID- 18324782
TI  - The salt dependence of the interferon regulatory factor 1 DNA binding domain
      binding to DNA reveals ions are localized around protein and DNA.
AB  - The equilibrium dissociation constant of the DNA binding domain of interferon
      regulatory factor 1 (IRF1 DBD) for its DNA binding site depends strongly on salt
      concentration and salt type. These dependencies are consistent with IRF1 DBD
      binding to DNA, resulting in the release of cations from the DNA and both release
      of anions from the protein and uptake of a cation by the protein. We demonstrated
      this by utilizing the fact that the release of fluoride from protein upon complex
      formation does not contribute to the salt concentration dependence of binding and
      by studying mutants in which charged residues in IRF1 DBD that form salt bridges
      with DNA phosphates are changed to alanine. The salt concentration dependencies
      of the dissociation constants of wild-type IRF1 DBD and the mutants R64A, D73A,
      K75A, and D73A/K75A were measured in buffer containing NaF, NaCl, or NaBr. The
      salt concentration and type dependencies of the mutants relative to wild-type
      IRF1 DBD provide evidence of charge neutralization by solution ions for R64 and
      by a salt bridge between D73 and K75 in buffer containing chloride or bromide
      salts. These data also allowed us to determine the number, type, and localization
      of condensed ions around both IRF1 DBD and its DNA binding site.

PMID- 18324783
TI  - Why clinically used tazobactam and sulbactam are poor inhibitors of OXA-10 beta
      lactamase: Raman crystallographic evidence.
AB  - The clinically used inhibitors tazobactam and sulbactam are effective in the
      inhibition of activity of class A beta-lactamases, but not for class D beta
      lactamases. The two inhibitors exhibit a complex multistep profile for their
      chemistry of inhibition with class A beta-lactamases. To compare the inhibition
      profiles for class A and D enzymes, the reactions were investigated within OXA-10
      beta-lactamase (a class D enzyme) crystals using a Raman microscope. The favored
      reaction pathway appears to be distinctly different from that for class A beta
      lactamases. In contrast to the case of class A enzymes that favor the formation
      of a key enamine species, the OXA-10 enzyme forms an alpha,beta-unsaturated
      acrylate (acid or ester). Quantum mechanical calculations support the likely
      product as the adduct of Ser115 to the acrylate. Few enamine-like species are
      formed by sulbactam or tazobactam with this enzyme. Taken together, our results
      show that the facile conversion of the initial imine, formed upon acylation of
      the active site Ser67, to the cis- and/or trans-enamine is disfavored. Instead,
      there is a significant population of the imine that could either experience cross
      linking to a second nucleophile (e.g., Ser115) or give rise to the alpha,beta
      unsaturated product and permanent inhibition. Alternatively, the imine can
      undergo hydrolysis to regenerate the catalytically active OXA-10 enzyme. This
      last process is the dominant one for class D beta-lactamases since the enzyme is
      not effectively inhibited. In contrast to sulbactam and tazobactam, the reactions
      between oxacillin or 6alpha-hydroxyisopropylpenicillinate (both substrates) and
      OXA-10 beta-lactamase appear much less complex. These compounds lead to a single
      acyl-enzyme species, the presence of which was confirmed by Raman and MALDI-TOF
      experiments.

PMID- 18324784
TI  - Amyloids of shuffled prion domains that form prions have a parallel in-register
      beta-sheet structure.
AB  - The [URE3] and [PSI (+)] prions of Saccharomyces cerevisiae are self-propagating
      amyloid forms of Ure2p and Sup35p, respectively. The Q/N-rich N-terminal domains
      of each protein are necessary and sufficient for the prion properties of these
      proteins, forming in each case their amyloid cores. Surprisingly, shuffling
      either prion domain, leaving amino acid content unchanged, does not abrogate the
      ability of the proteins to become prions. The discovery that the amino acid
      composition of a polypeptide, not the specific sequence order, determines prion
      capability seems contrary to the standard folding paradigm that amino acid
      sequence determines protein fold. The shuffleability of a prion domain further
      suggests that the beta-sheet structure is of the parallel in-register type, and
      indeed, the normal Ure2 and Sup35 prion domains have such a structure. We
      demonstrate that two shuffled Ure2 prion domains capable of being prions form
      parallel in-register beta-sheet structures, and our data indicate the same
      conclusion for a single shuffled Sup35 prion domain. This result confirms our
      inference that shuffleability indicates parallel in-register structure.

PMID- 18324785
TI  - Screening of 397 chemicals and development of a quantitative structure--activity
      relationship model for androgen receptor antagonism.
AB  - We have screened 397 chemicals for human androgen receptor (AR) antagonism by a
      sensitive reporter gene assay to generate data for the development of a
      quantitative structure-activity relationship (QSAR) model. A total of 523
      chemicals comprising data on 292 chemicals from our laboratory and data on 231
      chemicals from the literature constituted the training set for the model. The
      chemicals were selected with the purpose of representing a wide range of chemical
      structures (e.g., organochlorines and polycyclic aromatic hydrocarbons) and
      various functions (e.g., natural hormones, pesticides, plastizicers, plastic
      additives, brominated flame retardants, and roast mutagens). In addition, the
      intention was to obtain an equal number of positive and negative chemicals. Among
      our own data for the training set, 45.7% exhibited inhibitory activity against
      the transcriptional activity induced by the synthetic androgen R1881. The
      MultiCASE expert system was used to construct a QSAR model for AR antagonizing
      potential. A "5 Times, 2-Fold 50% Cross Validation" of the model showed a
      sensitivity of 64%, a specificity of 84%, and a concordance of 76%. Data for 102
      chemicals were generated for an external validation of the model resulting in a
      sensitivity of 57%, a specificity of 98%, and a concordance of 92% of the model.
      The model was run on a set of 176103 chemicals, and 47% were within the domain of
      the model. Approximately 8% of chemicals was predicted active for AR antagonism.
      We conclude that the predictability of the global QSAR model for this end point
      is good. This most comprehensive QSAR model may become a valuable tool for
      screening large numbers of chemicals for AR antagonism.

PMID- 18324786
TI  - Mitochondrial protein targets of thiol-reactive electrophiles.
AB  - Mitochondria serve a pivotal role in the regulation of apoptosis or programmed
      cell death. Recent studies have demonstrated that reactive electrophiles induce
      mitochondrion-dependent apoptosis. We hypothesize that covalent modification of
      specific mitochondrial proteins by reactive electrophiles serves as a trigger
      leading to the initiation of apoptosis. In this study, we identified protein
      targets of the model biotin-tagged electrophile probes N-iodoacetyl- N
      biotinylhexylene-diamine (IAB) and 1-biotinamido-4-(4'
      [maleimidoethylcyclohexane]carboxamido)butane (BMCC) in HEK293 cell mitochondrial
      fractions by liquid chromatography-tandem mass spectrometry (LC-MS-MS). These
      electrophiles reproducibly adducted a total of 1693 cysteine residues that mapped
      to 809 proteins. Protein modifications were selective in that only 438 cysteine
      sites in 1255 cysteinyl peptide adducts (35%) and 362 of the 809 identified
      protein targets (45%) were adducted by both electrophiles. Of these,
      approximately one-third were annotated to the mitochondria following protein
      database analysis. IAB initiated apoptotic events including cytochrome c release,
      caspase-3 activation, and poly(ADP-ribose)polymerase (PARP) cleavage, whereas
      BMCC did not. Of the identified targets of IAB and BMCC, 44 were apoptosis
      related proteins, and adduction site specificity on these targets differed
      between the two probes. Differences in sites of modification between these two
      electrophiles may reveal alkylation sites whose modification triggers apoptosis.

PMID- 18324787
TI  - Cross-linking of the DNA repair protein Omicron6-alkylguanine DNA
      alkyltransferase to DNA in the presence of antitumor nitrogen mustards.
AB  - The antitumor activity of chemotherapeutic nitrogen mustards including
      chlorambucil, cyclophosphamide, and melphalan is commonly attributed to their
      ability to induce DNA-DNA cross-links by consecutive alkylation of two
      nucleophilic sites within the DNA duplex. DNA-protein cross-linking by nitrogen
      mustards is not well characterized, probably because of its inherent complexity
      and the insufficient sensitivity of previous methodologies. If formed, DNA
      protein conjugates are likely to contribute to both target and off-target
      cytotoxicity of nitrogen mustard drugs. Here, we show that the DNA repair
      protein, O (6)-alkylguanine DNA alkyltransferase (AGT), can be readily cross
      linked to DNA in the presence of nitrogen mustards. Both chlorambucil and
      mechlorethamine induced the formation of covalent conjugates between (32)P
      labeled double-stranded oligodeoxynucleotides and recombinant human AGT protein,
      which were detected by SDS-PAGE. Capillary HPLC-electrospray ionization mass
      spectrometry (ESI-MS) analysis of AGT that had been treated with the guanine half
      mustards of chlorambucil or mechlorethamine revealed the ability of the protein
      to form either one or two cross-links to guanine. C145A AGT (a variant containing
      a single point mutation in the protein's active site) was found capable of
      forming a single guanine conjugate, while cross-linking was virtually abolished
      upon treatment of the C145A/C150S AGT double mutant with the guanine half
      mustards. HPLC-ESI (+)-MS/MS sequencing of tryptic peptides obtained from the
      wild-type AGT protein that had been treated with nitrogen mustards in the
      presence of DNA confirmed that the cross-linking took place between the N7
      position of guanine in DNA and two active site residues within the AGT protein
      (Cys (145) and Cys (150)). The exact chemical structures of AGT-DNA cross-links
      induced by chlorambucil and mechlorethamine were identified as N-(2-[ S
      cysteinyl]ethyl)- N-(2-[guan-7-yl]ethyl)- p-aminophenylbuyric acid and N-(2-[ S
      cysteinyl]ethyl)- N-(2-[guan-7-yl]ethyl)methylamine, respectively, based upon
      HPLC-MS/MS analysis of protein hydrolysates in parallel with the corresponding
      amino acid conjugates prepared synthetically. Mechlorethamine-induced AGT-DNA
      conjugates were isolated from protein extracts of AGT-expressing CHO cells but
      not control cells, demonstrating that nitrogen mustards can cross-link the AGT
      protein to DNA in the presence of other nuclear proteins. Because AGT is
      overexpressed in many tumor types, further investigations of the potential role
      of AGT-DNA cross-linking in the antitumor and mutagenic activity of antitumor
      nitrogen mustards are warranted.

PMID- 18324788
TI  - Intermolecular peroxyl radical reactions during autoxidation of hydroxy and
      hydroperoxy arachidonic acids generate a novel series of epoxidized products.
AB  - We report on the identification of novel epoxide products formed during the
      autoxidative transformation of 15 S-hydroxy- and 15 S-hydroperoxy-eicosatetra-5
      Z,8 Z,11 Z,13 E-enoic acids (15 S-HETE and 15 S-HPETE). These epoxides account
      for about 20-30% of the polar compounds detected during the early stages of
      autoxidation. Their common structural features are retention of the original 15 S
      hydroxy or 15 S-hydroperoxy moiety with epoxidation of the 11 Z or 13 E double
      bonds in the conjugated diene of the starting material. Four main epoxyalcohol
      isomers were characterized from the hydroxy fatty acid 15 S-HETE, comprising two
      pairs of diastereomers with either an 11,12- trans or 13,14- trans epoxide
      functionality. Four main epoxyhydroperoxides identified from 15 S-HPETE comprised
      two pairs with cis or trans epoxide configuration at the 11,12 position. To
      account for these transformations, we propose a mechanism involving peroxyl
      radical dependent dimerization or oligomerization of the fatty acid hydroxy or
      hydroperoxy derivatives into covalent intermediates resulting in intermolecular
      transfer of oxygen from the peroxyl radical to the epoxide group. Autoxidation of
      [ (18)O 2]-15 S-HPETE carrying an O-18 labeled hydroperoxide showed that the
      11,12- cis epoxy oxygen of the epoxy-hydroperoxide product was enriched in the
      labeled oxygen, providing evidence that in part it was derived directly from the
      starting hydroperoxide and not from molecular oxygen. Thus, intermediate
      dimerization and possibly oligomerization of fatty acid peroxyl radicals provides
      a mechanism of epoxidation of fatty acid derivatives during lipid peroxidation
      and a potential route to other products including aldehydes formed via carbon
      chain cleavage.

PMID- 18324789
TI  - Albumin is the main nucleophilic target of human plasma: a protective role
      against pro-atherogenic electrophilic reactive carbonyl species?
AB  - The aim of this work was to study the metabolic fate of 4-hydroxy- trans-2
      nonenal (HNE) in human plasma, which represents the main vascular site of
      reactive carbonyl species (RCS) formation and where the main pro-atherogenic
      target proteins are formed. When HNE was spiked in human plasma, it rapidly
      disappeared (within 40 s) and no phase I metabolites were detected, suggesting
      that the main fate of HNE is due to an adduction mechanism. HNE consumption was
      then monitored in two plasma fractions: low molecular weight plasma protein
      fractions (<10 kDa; LMWF) and high molecular weight plasma protein fractions (>10
      kDa; HMWF). HNE was almost stable in LMWF, while in HMWF it was consumed by
      almost 70% within 5 min. Proteomics identified albumin (HSA) as the main protein
      target, as further confirmed by a significantly reduced HNE quenching of
      dealbuminated plasma. LC-ESI-MS/MS analysis identified Cys34 and Lys199 as the
      most reactive adduction sites of HSA, through the formation of a Michael and
      Schiff base adducts, respectively. The rate constant of HNE trapping by albumin
      was 50.61 +/- 1.89 M (-1) s (-1) and that of Cys34 (29.37 M (-1) s (-1)) was 1
      order of magnitude higher with respect to that of GSH (3.81 +/- 0.17 M (-1) s (
      1)), as explained by molecular modeling studies. In conclusion, we suggest that
      albumin, through nucleophilic residues, and in particular Cys34, can act as an
      endogenous detoxifying agent of circulating RCS.

PMID- 18324790
TI  - Theoretical thermodynamics for large molecules: walking the thin line between
      accuracy and computational cost.
AB  - The thermodynamic properties of molecules are of fundamental interest in physics,
      chemistry, and biology. This Account deals with the developments that we have
      made in the about last five years to find quantum chemical electronic structure
      methods that have the prospect of being applicable to larger molecules. The
      typical target accuracy is about 0.5-1 kcal mol(-1) for chemical reaction and 0.1
      kcal mol(-1) for conformational energies. These goals can be achieved when a few
      physically motivated corrections to first-principles methods are introduced to
      standard quantum chemical techniques. These do not lead to a significantly
      increased computational expense, and thus our methods have the computer hardware
      requirements of the corresponding standard treatments. Together with the use of
      density-fitting (RI) integral approximations, routine computations on systems
      with about 100 non-hydrogen atoms (2000-4000 basis functions) can be performed on
      modern PCs. Our improvements regarding accuracy are basically due to the use of
      modified second-order perturbation theory to account for many-particle (electron
      correlation) effects. Such nonlocal correlations are responsible for important
      parts of the interaction in and between atoms and molecules. A common example is
      the long-range dispersion interaction that lead to van der Waals complexes, but
      as shown here also the conventional thermodynamics of large molecules is
      significantly influenced by intramolecular dispersion effects. We first present
      the basic theoretical ideas behind our approaches, which are the spin-component
      scaled Moller-Plesset perturbation theory (SCS-MP2) and double-hybrid density
      functionals (DHDF). Furthermore, the effect of the independently developed
      empirical dispersion correction (DFT-D) is discussed. Together with the use of
      large atomic orbital basis sets (of at least triple- or quadruple-zeta quality),
      the accuracy of the new methods is even competitive with computationally very
      expensive coupled-cluster methods, but they still remain routinely applicable for
      day-to-day chemical problems. This is demonstrated for the G3/99 benchmark set of
      heats of formation, 34 organic isomerization energies, and barriers for a number
      of pericyclic reactions. As an electronically complicated example, the relative
      energies of three isomeric Au(8) clusters are considered. In general, we
      recommend the very robust B2PLYP-D density functional approach for heat of
      formation calculations and for electronically complicated situations like
      transition metal complexes or open-shell species. With B2PLYP-D, an unprecedented
      low mean absolute deviation for the G3/99 test set with a DFT approach of 1.7
      kcal mol(-1) has been achieved. For closed-shell main-group molecules and many
      relative energies, SCS-MP2 is the method of choice, because it completely avoids
      the self-interaction error problem that still plagues current DFT. In critical
      cases, it is recommended to apply SCS-MP2 and B2PLYP-D simultaneously, where also
      the comparison with standard MP2 and density functionals like B3LYP may lead to
      additional insight.

PMID- 18324791
TI  - Gas-phase proton-transfer chemistry coupled with TOF mass spectrometry and ion
      mobility-MS for the facile analysis of poly(ethylene glycols) and PEGylated
      polypeptide conjugates.
AB  - Gas-phase ion/molecule chemistry has been combined with ion mobility separation
      and time-of-flight mass spectrometry to enable the characterization of large
      poly(ethylene glycol)s (PEGs) and PEGylated molecules (>40 kDa). A facile method
      is presented in which gas-phase superbases are reacted in the high-pressure
      source region of commercial TOF mass spectrometers to manipulate the charge
      states of large ions generated by electrospray ionization (ESI). Charge stripping
      decreases the spectral congestion typically observed in ESI mass spectra of high
      molecular weight polydisperse PEGylated molecules. From these data, accurate
      average molecular weights and molecular weight distributions for synthetic
      polymers and PEGylated proteins are determined. The average MW measured for
      PEGylated Granulocyte colony-stimulating factor (rh-GCSF, 40 726.2 Da) is in good
      agreement with the theoretical value, and a 16 Da mass shift is easily observed
      in the spectrum of an oxidized form of the heterogeneous PEGylated protein. Ion
      mobility separations can fractionate PEGs of different chain length; when coupled
      with charge stripping ion/molecule reactions, ion mobility mass spectrometry
      (IMMS) offers several analytical advantages over mass spectrometry alone for the
      characterization of large PEGylated molecules including enhanced dynamic range,
      increased sensitivity, and specificity. Low abundance free PEG in a PEGylated
      peptide preparation, which is not directly detectable by mass spectrometry, can
      be easily observed and accurately quantified with gas-phase ion/molecule
      chemistry combined with ion mobility mass spectrometry.

PMID- 18324792
TI  - Capillary electrophoresis, mass spectrometry, and UV-visible absorption studies
      on electrolyte-induced fractionation of gold nanoclusters.
AB  - We describe a novel and simple electrolyte-induced fractionation method to
      separate a polydisperse water-soluble gold nanocluster (Au NC) product. Different
      particle sizes of Au NC fractions can be easily centrifuged down as a function of
      the electrolyte concentration or lipophilicity of the solution. The changes in
      the absorption characteristic of the Au NC fractions under different
      electrolyte/ethanol conditions demonstrate the change in particle size
      distribution of the Au NC. Small gold nanoclusters, Au10, Au11, Au12, and Au15,
      were separated from the Au10-Au50 polydisperse Au NC product under various
      phosphate/ethanol conditions. The core size separation of Au NC was evaluated by
      their migration trends in capillary zone electrophoresis, UV-visible absorption,
      and mass spectra. The electrolyte-induced fractionation not only provides a
      convenient method to separate small Au NC mixture but also assists in the study
      of the photophysical properties of smaller Au NCs that are present with the
      larger Au NCs in a polydisperse Au NC product.

PMID- 18324793
TI  - Anion-exchange chromatographic separation of Hg for isotope ratio measurements by
      multicollector ICPMS.
AB  - A procedure is described for precise Hg isotope ratio measurements by solution
      nebulization multicollector inductively coupled plasma mass spectrometry (MC
      ICPMS). Hg was released from geological samples using aqua regia extraction and
      then separated from other matrix elements with the aid of anion-exchange
      chromatography using strongly basic Dowex 1-X8 anion-exchange resin. Performance
      of the chromatographic procedure was evaluated using various types of replacement
      anions for elution of mercury, including l-cysteine, thiourea, NO3-, and SO42-. A
      solution of 0.15% l-cysteine in 0.06 M HCl was found to be the most convenient
      eluent for subsequent MC-ICPMS measurements. The optimized procedure provides
      separation of Hg from virtually all concomitant matrix elements while maintaining
      quantitative (>95%) recovery. In addition, band displacement chromatographic
      experiments were conducted to assess whether the anion-exchange purification can
      produce Hg isotope fractionation artifacts. No isotope fractionation between the
      Hg(II)-l-cysteine complex in aqueous solution and Hg ions in the anion-exchange
      resin was observed. Hg isotope ratio measurements were performed using the
      bracketing standards approach and on-line correction for instrumental mass
      discrimination using Tl spiking and normalization to the 205Tl/203Tl ratio. The
      absence of spectral interference during Hg isotope ratio measurements was
      verified using a three-isotope plot. Uncertainties of Hg isotope ratio
      measurements for replication of the entire procedure, expressed as two standard
      deviations, are better than +/-0.08 per thousand/amu. The described procedure
      facilitates study of variations in the isotopic composition of Hg in nature.

PMID- 18324794
TI  - Modified silver nanoparticle as a hydrophobic affinity probe for analysis of
      peptides and proteins in biological samples by using liquid-liquid
      microextraction coupled to AP-MALDI-ion trap and MALDI-TOF mass spectrometry.
AB  - A new approach of using modified silver nanoparticles (AgNPs) in toluene as
      hydrophobic affinity probes for the separation and preconcentration of peptides
      and proteins in biological samples prior to atmospheric pressure-matrix assisted
      laser desorption/ionization (AP-MALDI) ion trap mass spectrometry and matrix
      assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry
      has been successfully demonstrated. To our best knowledge, for the first time,
      the modified AgNPs with hydrophobic ligands, such as dodecanethiol (DT) and
      octadecanethiol (OT) in toluene, were used for the liquid-liquid microextraction
      (LLME) of peptides and proteins through the hydrophobic interactions. In the
      present investigation, gramicidin was chosen as a model compound to assess the
      hydrophobic extraction with the modified AgNPs. The optimum extraction efficiency
      of gramicidine was observed at pH 7.0 for 1.5 h of extraction time with 7%
      addition of salt. Compared to the conventional use of AP-MALDI-MS, a 266-388-fold
      improvement in the limit of detection (LOD) for gramicidin was obtained in urine
      and plasma samples. The lowest concentration of gramicidin that was detected by
      using modified AgNPs in urine and plasma samples was 0.13 and 0.16 microM,
      respectively. Furthermore, the proposed method was demonstrated for the
      extraction of other long chain proteins, like myoglobin, ubiquitin, and bovine
      serum albumin, in a sample solution by matrix assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The major
      feature of the newly synthesized modified AgNPs was that the target species could
      be efficiently separated and preconcentrated without sample loss prior to MALDI
      MS detection for the sensitive and effective analysis of peptides and proteins in
      biological samples.

PMID- 18324795
TI  - Shared and closed-shell O-O interactions in silicates.
AB  - Bond paths of maximum electron density spanning O-O edges shared between
      equivalent or quasiequivalent MOn (n > 4) coordination polyhedra are not uncommon
      electron density features displayed by silicates. On the basis of the positive
      values for the local electronic energy density, H(rc), at the bond critical
      points, rc, they qualify as weak "closed-shell" interactions. As observed for M-O
      bonded interactions (M = first and second row metal atoms), the electron density,
      rho(rc), and the Laplacian of the electron density increase in a regular way as
      the separation between the O atoms, R(O-O), decreases. A simple model, based on
      R(O-O) and the distances of the Si atoms from the midpoint between adjacent pairs
      of O atoms, partitions the O-O bond paths in the high-pressure silica polymorph
      coesite into two largely disjoint domains, one with and one without bond paths.
      The occurrence of O-O bond paths shared in common between equivalent coordination
      polyhedra suggests that they may be grounded in some cases on factors other than
      bonded interactions, particularly since they are often displayed by inert
      procrystal representations of the electron density. In these cases, it can be
      argued that the accumulation of the electron density along the paths has its
      origin, at least in part, in the superposition of the peripheral electron density
      distributions of the metal M atoms occupying the edge-sharing polyhedra. On the
      other hand, the accumulation of electron density along the paths may stabilize a
      structure by shielding the adjacent M atoms in the edge-sharing polyhedra. For
      closed-shell Li-O, Na-O, and Mg-O interactions, H(rc) is positive and increases
      as the value of rho(rc) increases, unlike the "shared" Be-O, B-O, C-O, Al-O, Si
      O, P-O, and S-O interactions, where H(rc) is negative and decreases as rho(rc)
      increases. The H(rc) values for the weak closed-shell O-O interactions also
      increase as rho(rc) increases, as observed for the closed-shell M-O interactions.
      On the basis of the bond critical point properties and the negative H(rc) value,
      the O-O interaction comprising the O2 molecule in silica III qualifies as a
      shared interaction.

PMID- 18324796
TI  - Theoretical studies on the magnetic bistability of dinickel complex tuned by
      azide.
AB  - The magnetic-structural correlation in magnetic switchable dinickel(II) complex
      [LNi2(N3)3] (L- is a pyrazolate-based compartmental ligand) has been investigated
      on the basis of various unrestricted density functional theory (UDFT) combined
      with the broken symmetry (BS) approach. The calculated exchange coupling
      constants were in good agreement with experimental result by using the PBE0
      method with LANL2DZ basis set. The antiferromagnetic interaction between the
      Ni(II) ions is mainly due to the large energy difference of the singly occupied
      molecular orbitals (SOMOs), and the p orbital overlap for nitrogen atoms on azido
      and the pyrazolate bridge groups. The analysis of the spin density distribution
      reveals that both the spin polarization and spin delocalization contribute to the
      antiferromagnetic interaction. Furthermore, the bistable magnetic behavior for
      this system (strong antiferromagnetic interaction in low-temperature phase and
      the week antiferromagnetic in high-temperature phase) results from the change of
      the Ni-NNN-Ni dihedral angle (tau) in mu1,3-N3. The increase of tau is the key
      role in decreasing the SOMOs energy difference and weakening the
      antiferromagnetic interaction. Therefore, the abrupt modulation of the magnitude
      of M-NNN-M dihedral angle tau in the binuclear-azide complex by external
      perturbations provides new possibilities for the design of molecular magnetic
      switching devices.

PMID- 18324797
TI  - 2,3-Diphenylbutadiene and donor-acceptor functionalized derivatives: exploring
      the competition between conjugation paths in branched pi-systems.
AB  - 2,3-Diphenylbutadiene and its donor-acceptor functionalized derivatives represent
      branched pi systems consisting of three overlapping linearly conjugated units,
      namely a 1,3-butadiene and two phenylethene subsystems. The evaluation of pi
      conjugation using a scheme based on the natural bond orbital analysis shows that
      the details of the structure of these compounds is governed by electron
      delocalization. The potential energy surface of 2,3-diphenylbutadiene shows two
      minima, each one representing a distinct combination of conjugation patterns.
      These minima are shown to be connected by a low-energy path with transition
      structures that have one conjugation path fully activated, while conjugation is
      completely disrupted along the other path. We will show that, in response to
      donor-accptor functionalization, the 2,3-diphenylbutadiene backbone will switch
      to other conformations, which come along with substantial changes in the
      electronic structure.

PMID- 18324798
TI  - On the spectacular structural isomorphism between CnHs monoradical and Cn+sHs+3
      diradical benzenoid hydrocarbons: from reactive intermediates to vacancy (Hole)
      defects in graphite.
AB  - The formula/structure informatics of monoradical and diradical benzenoid
      hydrocarbons that are potential reactive intermediates is studied. Some new
      enumeration and structural results with analytical expressions are presented. The
      topological paradigm and one-to-one correspondence between the monoradical and
      diradical constant-isomer series is demonstrated. Constant-isomer benzenoid
      monoradicals of the formula CnHs have a one-to-one correspondence in isomer
      number and topology to constant-isomer diradicals of the formula Cn+sHs+3. Some
      electronic properties of benzenoid radicals are delineated. Excising out a
      monoradical or diradical benzenoid carbon molecule from a perfect hexagonal
      graphite layer leaves a matching monoradical or diradical vacancy hole defect
      called an antimolecule; this observation can be generalized to include excising
      out all nondisjoint and obvious benzenoid polyradicals from a perfect (Kekulean)
      hexagonal graphite layer. It is shown that the characteristics of graphite
      vacancies (antimolecules) can be deduced from knowledge about the carbon
      molecules removed in their formation.

PMID- 18324799
TI  - Cross-docking of inhibitors into CDK2 structures. 1.
AB  - Predicting protein/ligand binding affinity is one of the most challenging
      computational chemistry tasks. Numerous methods have been developed to address
      this challenge, but they all have limitations. Failure to account for protein
      flexibility has been a shortcoming of many methods. In this cross-docking study
      the data set comprised 150 inhibitor complexes of the protein kinase CDK2. Gold
      and Glide performed well in terms of docking accuracy. The chance of cross
      docking a ligand within a 2 A RMSD of its experimental pose was found to be 50%.
      Relative binding potency was not properly predicted from scoring functions, even
      though cross-docking of each inhibitor into each protein structure was performed
      and only scores of correctly docked ligands were considered. An accompanying
      paper (Voigt, J. H.; Elkin, C.; Madison, V. S. Duca, J. S. J. Chem. Inf. Model.
      2008, 48, 669-678) covers cross-docking and docking accuracy from the perspective
      of using multiple protein structures.

PMID- 18324800
TI  - Cross-docking of inhibitors into CDK2 structures. 2.
AB  - In the preceding paper (Duca, J. S.; Madison, V. S.; Voigt, J. H. J. Chem. Inf.
      Model. 2008, 48, 659-668), the accuracy of docking and affinity predictions of
      the Gold and Glide programs were investigated using single protein conformations
      spanning 150 CDK2/inhibitor crystallographic complexes. High docking accuracy was
      observed with both methods; furthermore, Glide showed modest log(IC50)/score
      correlations. In this part of the study, the effect of combining docking results
      from multiple protein conformations in a consensus fashion was probed. This
      approach enhanced docking accuracy only for Glide, which was attributed to the
      nature of its scoring function. For log(IC50)/score correlations, particular
      emphasis was placed on considering only scores from correctly docked poses. Using
      multiple instead of single protein structures showed an improvement in the
      correlations. Validation sets and scrambling experiments were used to examine the
      statistical significance and predictivity of these correlations. Rather than
      actual improvements in scoring accuracy, docking to multiple protein
      conformations produced overfitting artifacts.

PMID- 18324801
TI  - Probing of lipase activity at air/water interface by sum-frequency generation
      spectroscopy.
AB  - The infrared-visible sum-frequency generation (SFG) vibrational spectroscopy was
      used to probe enzymatic activity of Thermomyces lanuginosus lipase (TLL) at
      air/water interface. A monolayer of amphiphilic O-palmitoyl-2,3
      dicyanohydroquinone (PDCHQ), containing target ester group and two CN groups
      serving as vibrational markers, was utilized as an enzyme substrate. SFG data
      revealed the detailed molecular scale structure and properties of the PDCHQ layer
      at the interface. In particular, we demonstrate that hydrophilic headgroup of
      PDCHQ is mainly in the form of an oxyanion, and the enzyme-induced cleavage of
      the ester bond could be spectroscopically monitored by the disappearance of the
      intense C tripple bond N resonance at 2224 cm(-1). The enzymatic nature of the
      ester bond cleavage was confirmed by the control experiments with deactivated
      S146A mutant variant of TLL. By comparing action of wild type (WT) TLL and its
      inactive S146A mutant, it was shown that two effects take place at the interface:
      disordering of the lipid monolayer due to the adsorption of enzyme and enzymatic
      cleavage of the ester bond. The concentration of enzyme as low as 10 nM could be
      easily sensed by the SFG spectroscopy. We present spectroscopic evidence that
      upon hydrolysis one of the products, 2,3-dicyanohydroquinone, leaves the surface,
      while the other, palmitic acid, remains at air/water interface in predominantly
      undissociated form with the mono-hydrogen-bonded carbonyl group. Strong amide I
      (1662 cm(-1)) and amide A (3320 cm(-1)) SFG signals from TLL suggest that enzyme
      molecules position themselves at air/water interface in an orderly fashion.
      Presented work demonstrates the potential of SFG spectroscopy for in situ real
      time monitoring of enzymatic processes at air/water interface.

PMID- 18324802
TI  - Monte Carlo simulation of electrodeposition of copper: a multistep free energy
      calculation.
AB  - Electrodeposition of copper (Cu) involves length scales of a micrometer or even
      less. Several theoretical techniques such as continuum Monte Carlo, kinetic Monte
      Carlo (KMC), and molecular dynamics have been used for simulating this problem.
      However the multiphenomena characteristics of the problem pose a challenge for an
      efficient simulation algorithm. Traditional KMC methods are slow, especially when
      modeling surface diffusion with large number of particles and frequent particle
      jumps. Parameter estimation involving thousands of KMC runs is very time
      consuming. Thus a less time-consuming and novel multistep continuum Monte Carlo
      simulation is carried out to evaluate the step wise free energy change in the
      process of electrochemical copper deposition. The procedure involves separate
      Monte Carlo codes employing different random number criterion (using hydrated
      radii, bare radii, hydration number of the species, redox potentials, etc.) to
      obtain the number of species (CuCl(2) or CuSO(4) or Cu as the case may be) and in
      turn the free energy. The effect of concentration of electrolyte, influence of
      electric field and presence of chloride ions on the free energy change for the
      processes is studied. The rate determining step for the process of
      electrodeposition of copper from CuCl(2) and CuSO(4) is also determined.

PMID- 18324803
TI  - Water/hydrocarbon interfaces: effect of hydrocarbon branching on single-molecule
      relaxation.
AB  - Water/hydrocarbon interfaces are studied using molecular dynamics simulations in
      order to understand the effect of hydrocarbon branching on the dynamics of the
      system at and away from the interface. A recently proposed procedure for studying
      the intrinsic structure of the interface in such systems is utilized, and
      dynamics are probed in the usual laboratory frame as well as the intrinsic frame.
      The use of these two frames of reference leads to insight into the effect of
      capillary waves at the interface on dynamics. The systems were partitioned into
      zones with a width of 5 A, and a number of quantities of dynamical relevance,
      namely, the residence times, mean squared displacements, the velocity auto
      correlation functions, and orientational time correlations for molecules of both
      phases, were calculated in the laboratory and intrinsic frames at and away from
      the interface. For the aqueous phase, translational motion is found to be (a)
      diffusive at long times and not anomalous as in proteins or micelles, (b) faster
      at the interface than in the bulk, and (c) faster upon reduction of the effect of
      capillary waves. The rotational motion of water is (a) more anisotropic at the
      interface than in the bulk and (b) dependent on the orientation of the covalent O
      H bond with respect to the plane of the interface. The effect of hydrocarbon
      branching on aqueous dynamics was found to be small, a result similar to the
      effect on the interfacial water structure. The hydrocarbon phase shows a larger
      variation for all dynamical probes, a trend consistent with their interfacial
      structure.

PMID- 18324804
TI  - Adsorption of H2O, CO2 and Xe on Soft Surfaces.
AB  - The interactions of water, carbon dioxide, and Xe with octadecanethiol
      (C(18)H(37)SH, ODT) self-assembled monolayers (SAMs) were studied under ultrahigh
      vacuum conditions employing temperature-programmed desorption and optical
      diffraction measurements. The ODT layer was grown on a 1 nm thick gold film
      deposited over a Ru(001) single-crystal substrate. The gases used in this report
      differ in their lateral interactions while adsorbed on ODT-SAM being either
      repulsive (Xe) or attractive (H(2)O, CO(2)). The activation energies for
      desorption of the first layer from ODT are E(a) = 3.6 +/- 0.9, 4.1 +/- 0.5, and
      8.5 +/- 0.9 kcal/mol for Xe, CO(2), and H(2)O, respectively. Sticking
      probabilities of the three gases on the soft ODT surface are S(0) = 0.7 +/- 0.1,
      0.8 +/- 0.1, and 0.95 +/- 0.05 for xenon, CO(2), and water, respectively, derived
      from the respective adsorption curves. Optical diffraction studies from
      multilayer coverage grating of Xe on ODT-SAM have demonstrated that sublimation
      is a thermodynamically more favorable process over diffusion and wetting. The
      significantly lower binding energy of the first layers of H(2)O and CO(2)
      adsorbed on the soft surface of ODT compared to that on clean metals and oxides,
      reflects generally weak (CO(2)) and hydrophobic (H(2)O) interactions that are
      important for understanding the behavior of these molecules on interfaces that
      are found in biological systems.

PMID- 18324805
TI  - Single-molecule study of lateral mobility of epidermal growth factor receptor
      2/HER2 on activation.
AB  - The transmembrane protein HER2, a member of the epidermal growth factor receptor
      family of tyrosine kinase, plays important roles in many fundamental cellular
      processes as well as the pathogenesis of many cancers. In this work, we have
      applied the single-molecule fluorescence microscopic method to study lateral
      mobility change of HER2 on activation by imaging and tracking individual GFP
      tagged HER2 molecules on the membrane of living cells. The single HER2 molecules
      displayed different diffusion rates and modes. It was interesting to find that
      the mobility of HER2 increased upon stimulation by heregulin beta1, the specific
      ligand of HER3. The faster diffusion was related to the tyrosine phosphorylation
      of HER2 or EGFR. The results provided new information for the understanding of
      HER2 activation and molecular mechanism of signal transduction through HER2/HER3
      heterodimerization.

PMID- 18324806
TI  - First-principle time-dependent study of magnesium-containing porphyrin-like
      compounds potentially useful for their application in photodynamic therapy.
AB  - Geometry optimization, singlet-triplet energy gap, and electronic absorption
      spectra calculation of complexes formed by Mg ion and porphyrin, porphyrazin,
      chlorine, bacteriochlorine, texaphyrin, phthalocyanine, naphthalocyanine, and
      anthracocyanine ligands have been carried out to elucidate their potentiality as
      photosensitizers in photodynamic therapy (PDT). The study has been performed
      employing the density functional theory (DFT) and its time-dependent approach
      (TDDFT) in conjunction with the PBE0 exchange-correlation functional and extended
      TZVP all-electron basis sets. The solvent effects have been evaluated throughout
      the polarizable continuum model (PCM). Results show that, following the
      properties requirement for the drugs used in PDT, the Mg-Tex and Mg-Pc complexes
      are reliable candidates for their use as photosensitizers in this medical
      therapy.

PMID- 18324807
TI  - Infrared reflection-absorption spectroscopy and polarization-modulated infrared
      reflection-absorption spectroscopy studies of the aequorin langmuir monolayer.
AB  - The Langmuir monolayer of aequorin and apoaequorin was studied by infrared
      reflection-absorption spectroscopy (IRRAS) and polarization-modulated IRRAS
      techniques. The alpha-helices in the aequorin Langmuir monolayer were parallel to
      the air-water interface at zero surface pressure. When the surface pressure
      increased to 15 mN.(m-1), the alpha-helices became tilted and the turns became
      parallel to the air-water interface. As for apoaequorin, the alpha-helices were
      also parallel to the air-water interface at 0 mN.m(-1). However, the alpha-helix
      became tilted and the turns became parallel to the air-water interface quickly at
      5 mN.m(-1). With further compression of the apoaequorin Langmuir monolayer, the
      orientation remained the same. The different behaviors of aequorin and
      apoaequorin at the air-water interface were explained by the fact that aequorin
      formed dimers at the air-water interface but apoaequorin was a monomer. It is
      more difficult for a dimer to be tilted by the compression of the Langmuir
      monolayer.

PMID- 18324808
TI  - On the difference between foams stabilized by surfactants and whole casein or
      beta-casein. comparison of foams, foam films, and liquid surfaces studies.
AB  - This research work aims to investigate the behavior of a mixed system composed of
      a commercial protein (whole casein) and a low molecular weight surfactant (Tween
      20) in order to understand its foam stability on the basis of fundamental surface
      quantities such as surface and disjoining pressure. These experiments prove to be
      extremely useful in the understanding of the processes determining foam
      stability. The complex behavior of whole casein/Tween 20 mixtures is directly
      deduced from the surface pressure isotherms. Concretely, the isotherm of the
      mixed system is displaced to smaller surfactant concentrations as compared to the
      pure surfactant system. This feature is quantified by a critical aggregation
      concentration and suggests formation of protein/surfactant complexes within the
      surface layer. The disjoining pressure isotherms of the pure and mixed systems
      provide key information regarding the structure and composition of the mixed
      whole casein/Tween 20 surface layers. Furthermore, they provide a direct
      correlation with the foam stability in terms of the thickness of the final foam
      film; the thinner the film, the less stable the foam. The experimental results
      are further discussed in terms of literature studies of similar systems, and a
      final rather accurate description of the system arises. This work investigates
      the importance of the nature of the protein in the stability of the foams of
      protein/surfactant mixtures and highlights the fundamental role of the surface
      properties in the understanding of such a major phenomenon in colloid science and
      technology.

PMID- 18324809
TI  - Low viscosity reversed hexagonal mesophases induced by hydrophilic additives.
AB  - This study reports on the formation of a low viscosity H(II) mesophase at room
      temperature upon addition of Transcutol (diethylene glycol mono ethyl ether) or
      ethanol to the ternary mixture of GMO (glycerol monooleate)/TAG
      (tricaprylin)/water. The microstructure and bulk properties were characterized in
      comparison with those of the low viscosity HII mesophase formed in the ternary
      GMO/TAG/water mixture at elevated temperatures (35-40 degrees C). We
      characterized the role of Transcutol or ethanol as inducers of disorder and
      surfactant mobility. The techniques used were rheology, differential scanning
      calorimetry (DSC), wide- and small-angle X-ray scattering (WAXS and SAXS,
      respectively), NMR (self-diffusion and (2)H NMR), and Fourier transform infrared
      (FTIR) spectroscopies. The incorporation of either Transcutol or ethanol induced
      the formation of less ordered HII mesophases with smaller domain sizes and
      lattice parameters at room temperature (up to 30 degrees C), similar to those
      found for the GMO/TAG/water mixture at more elevated temperatures (35-40 degrees
      C). On the basis of our measurements, we suggest that Transcutol or ethanol
      causes dehydration of the GMO headgroups and enhances the mobility of the GMO
      chains. As a result, these two small molecules, which compete for water with the
      GMO polar headgroups, may increase the curvature of the cylindrical micelles and
      also perhaps reduce their length. This results in the formation of fluid H(II)
      structures at room temperature (up to 30 degrees C). It is possible that these
      phases are a prelude to the H(II)-L(2) transformation, which takes place above 35
      degrees C.

PMID- 18324810
TI  - Water diffusion in nanoporous glass: an NMR study at different hydration levels.
AB  - By pulsed field gradient nuclear magnetic resonance measurements, we investigated
      the translational diffusion of water confined in the 200 A diameter pores of a
      sol-gel silica glass. The experiments, performed as a function of the hydration
      level, showed an enhancement of the self-diffusion coefficient when the water
      content corresponds to one or fewer monolayers. An explanation for this
      occurrence has been given in terms of a two-phase process involving a fast
      molecular exchange between the liquid and the vapor phase. Moreover, in partially
      filled pores, the surface water diffusion coefficient was measured, and was 4
      times lower than the diffusion of liquid confined water in saturated spaces.

PMID- 18324811
TI  - Fluorescence behavior and specific interactions of an ionic liquid in ethylene
      glycol derivatives.
AB  - The excitation-wavelength- and concentration-dependent fluorescence response of
      an ionic liquid (IL), 1-octyl-3-methylimidazolium tetrafluoroborate
      [Omim][BF(4)], in the ethylene glycol derivatives, [CH(3)(OCH(2)CH(2))n-OH, n = 1
      3], has been critically examined in the entire composition range. The pure IL
      exhibited a large red shift beyond an excitation wavelength of 390 nm, showing
      the heterogeneous nature of the liquid. Concentration dependence of the
      fluorescence spectra in the organic solvent-rich region favors the association of
      IL molecules into the aggregated structures. The maximum of the fluorescence
      spectra shifted toward blue with the increase of organic component concentration
      in all of the mixtures, reflecting an appreciable solute-solvent interaction.
      Very high concentrations of the organic liquid in the mixtures resulted in the
      inversion of the spectral shift toward red, indicating the dominance of pi-pi*
      transitions over the n-pi* transitions as a consequence of imidazolium ring
      stacking. (1)H NMR and FT-IR investigations over the whole composition range of
      the mixtures showed multiple hydrogen-bonded interactions of varying strengths
      between the unlike molecules and the existence of associated species of the IL in
      the dilute region. Both the specific interactions between unlike molecules and
      the tendency of aggregation of IL molecules in the dilute region reduced with the
      introduction of the -OC(2)H(4) group in the glycol derivative. A comparison of
      specific interactions with the volumetric properties of the similar mixtures
      shows that the packing efficiency depending on differences in the shape and size
      of the molecules mainly decides the overall magnitude of deviations from
      ideality.

PMID- 18324812
TI  - Ozonolysis of uric acid at the air/water interface.
AB  - Uric acid (UA) epoxide, peroxide, and ozonide species produced in aqueous UA
      microdroplets exposed to O(3)(g) are detected by online mass spectrometry within
      approximately 1 ms. UA conversions are independent of its initial concentration
      below approximately 0.1 mM and are unaffected by addition of excess H(2)O(2) or t
      butanol. UA reactivity increases approximately 380 times from pH 4 to 7, which is
      at variance with the pH-independent rates reported for the UA + O(3)(aq) reaction
      in bulk water. At pH approximately 7, UA and ascorbic acid (AH(2)) microdroplets
      react with O(3)(g) at similar rates, although UA is approximately 40 times more
      reactive than AH(2) toward O(3)(aq) in bulk water. Only the UA epoxide, plus
      traces of UA peroxide, are formed upon mixing UA(aq) and O(3)(aq) solutions. We
      infer that the gas-liquid ozonolysis of UA proceeds in an interfacial aqueous
      medium quite distinct from bulk water. Thus, UA, a component of the pulmonary
      epithelial lining fluid that scavenges atmospheric O(3)(g) into less deleterious
      species (similar to AH(2)), is rendered inactive below pH approximately 5. The
      potential implications of these findings on synergistic health effects between
      tropospheric ozone and acidic particulates are briefly analyzed.

PMID- 18324813
TI  - Two-dimensional graphene nanoribbons.
AB  - A new synthetic strategy toward novel linear two-dimensional graphene nanoribbons
      up to 12 nm has been established. The nanoribbons are characterized by MS,
      UV/vis, and scanning tunneling microscopy (STM). Various microscopic studies of
      these novel structures showed a high tendency to self-assemble.

PMID- 18324814
TI  - Dithiomethylether as a ligand in the hydrogenase h-cluster.
AB  - An X-ray crystallographic refinement of the H-cluster of [FeFe]-hydrogenase from
      Clostridium pasteurianum has been carried out to close-to atomic resolution and
      is the highest resolution [FeFe]-hydrogenase presented to date. The 1.39 A,
      anisotropically refined [FeFe]-hydrogenase structure provides a basis for
      examining the outstanding issue of the composition of the unique nonprotein
      dithiolate ligand of the H-cluster. In addition to influencing the electronic
      structure of the H-cluster, the composition of the ligand has mechanistic
      implications due to the potential of the bridge-head gamma-group participating in
      proton transfer during catalysis. In this work, sequential density functional
      theory optimizations of the dithiolate ligand embedded in a 3.5-3.9 A protein
      environment provide an unbiased approach to examining the most likely composition
      of the ligand. Structural, conformational, and energetic considerations indicate
      a preference for dithiomethylether as an H-cluster ligand and strongly disfavor
      the dithiomethylammonium as a catalytic base for hydrogen production.

PMID- 18324815
TI  - A structure-permeability relationship of ultrathin nanoporous silicon membrane: a
      comparison with the nuclear envelope.
AB  - We report on a simple, quantitative relationship between structure and
      permeability of a novel ultrathin nanoporous membrane based on nanocrystalline
      silicon. Large permeability of the free-standing nanomembrane to Ru(NH3)63+, O2,
      or 1,1'-ferrocenedimethanol, which was able to be measured for the first time by
      employing scanning electrochemical microscopy, is proportional to the density (67
      mum-2) and average radius (5.6 nm) of nanopores. As solution electrolyte
      concentration decreases down to 0.01 M, the nanopores are selectively "closed"
      against Fe(CN)64- because of electrostatic repulsion against negative charges at
      the pore wall. Permeability of the silicon nanomembrane was compared to
      permeability of the nuclear envelope to find that the channel diameter of the
      nuclear pore complex that perforates the nuclear envelope is much larger than the
      average diameter of the silicon nanopores and concomitantly a hypothetical
      diameter of 10 nm.

PMID- 18324816
TI  - An RNA aptamer-based electrochemical biosensor for detection of theophylline in
      serum.
AB  - An electrochemical RNA aptamer-based biosensor for rapid and label-free detection
      of the bronchodilator theophylline was developed. The 5'-disulfide-functionalized
      end of the RNA aptamer sequence was immobilized on a gold electrode, and the 3'
      amino-functionalized end was conjugated with a ferrocene (Fc) redox probe. Upon
      binding of theophylline the aptamer switches conformation from an open unfolded
      state to a closed hairpin-type conformation, resulting in the increased electron
      transfer efficiency between Fc and the electrode. The electrochemical response,
      which was measured by differential pulse voltammetry, reaches saturation within a
      few minutes after addition of theophylline, and the dynamic range for detecting
      theophylline is 0.2-10 muM. The electrode displays an inhibited response when
      applied directly in serum samples treated with RNase inhibitors; however a full
      response to the theophylline serum concentration was obtained by transferring the
      electrode to blank serum-free buffer solutions. It was demonstrated that
      theophylline is detected with high selectivity in the presence of caffeine and
      theobromine.

PMID- 18324817
TI  - Cleavage and isomerization of UpU promoted by dinuclear metal ion complexes.
AB  - The catalysis of phosphoryl transfer by metal ions has been intensively studied
      in both biological and artificial systems, but the status of the transient
      pentacoordinate phosphoryl species (as transition state or intermediate) is the
      subject of considerable debate. We report that dinuclear metal ion complexes that
      incorporate second sphere hydrogen bond donors not only promote the cleavage of
      RNA fragments just as efficiently as the activated analogue HPNPP but also
      provide the first examples of metal ion catalyzed phosphate diester isomerization
      close to neutral pH. This observation implies that the reaction catalyzed by
      these complexes involves the formation of a phosphorane intermediate that is
      sufficiently long-lived to pseudorotate.

PMID- 18324818
TI  - Demonstration of molecular assembly on Si (100) for CMOS-compatible molecule
      based electronic devices.
AB  - In this work, we establish the potential of a UV-promoted direct attachment of
      alkanes with alcohol and thiol linkers to the silicon (100) surfaces for use in
      molecular electronic devices with increased potential for integration with
      existing CMOS technologies. Characterization of the self-assembled monolayers via
      Fourier transform infrared spectroscopy, spectroscopic ellipsometry, and X-ray
      photoemission spectroscopy shows that the films assembled on the Si (100) are
      comparable in quality, aliphatic monolayer coverage, and extent of substrate
      oxidation to those assembled on the more extensively studied Si (111) crystal
      face. Simple Si (100)-based electronic devices fabricated with the monolayers
      exhibited molecule-dependent electrical characteristics. These data highlight the
      effectiveness of the assembly on Si (100), the ability to fabricate enclosed Si
      (100)-based molecular devices, and the potential for the future integration of
      these devices with more conventional technologies.

PMID- 18324819
TI  - Synthesis of the AB subunit of angelmicin B through a tandem alkoxy radical
      fragmentation-etherification sequence.
AB  - The synthesis of the tricyclic enone 2, corresponding to the AB subunit of the
      novel tyrosine kinase inhibitor angelmicin B, is described. The strategy centers
      on an intramolecular Diels-Alder (IMDA) reaction on triene 4 to provide the
      complex decalin 3, which is elaborated to 2. Other key steps are the formation of
      the THF ring in 2 through a tandem alkoxy radical fragmentation-etherification on
      the lactol derived from 3, and the synthesis of 4 via a ring-closing ene-yne
      metathesis (RCEYM).

PMID- 18324820
TI  - Organocatalytic asymmetric total synthesis of (R)-rolipram and formal synthesis
      of (3S,4R)-paroxetine.
AB  - An efficient enantioselective total synthesis of (R)-rolipram and an efficient
      enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using
      the highly enantioselective Michael addition of malonate nucleophiles as key
      steps in both cases.

PMID- 18324821
TI  - A new sparteine surrogate for asymmetric deprotonation of N-Boc pyrrolidine.
AB  - The s-BuLi complex of a cyclohexane-derived diamine is as efficient as s-BuLi/(-)
      sparteine for the asymmetric deprotonation of N-Boc pyrrolidine. This is the
      first example of high enantioselectivity using a non-sparteine-like diamine in
      such reactions. The (S,S)-diamine is a useful (+)-sparteine surrogate and was
      utilized in short syntheses of (-)-indolizidine 167B and an intermediate for the
      synthesis of the CCK antagonist (+)-RP 66803.

PMID- 18324822
TI  - A multifaceted phosphate tether: application to the C15-C30 subunit of
      dolabelides A-D.
AB  - Construction of the C15-C30 subunit of dolabelide utilizing a temporary phosphate
      tether is described. Two routes are reported that make use of the orthogonal
      protecting- and leaving-group properties innate to phosphate esters. One route
      relies on a selective terminal oxidation, while a second utilizes a CM/selective
      hydrogenation sequence. Both routes depend on a highly regio- and
      diastereoselective cuprate addition to set the requisite stereochemistry at C22.

PMID- 18324823
TI  - Urceolatin, a structurally unique bromophenol from Polysiphonia urceolata.
AB  - 6-Bromo-1-(3-bromo-4,5-dihydroxybenzyl)phenanthro[4,5-bcd]furan-2,3,5-triol
      (urceolatin, 1), a highly oxygenated bromophenol containing an unprecedented
      naturally occurring benzylphenanthro[4,5-bcd]furan unit, was isolated from the
      marine red alga Polysiphonia urceolata. Its structure was established on the
      basis of extensive spectroscopic analysis. Compound 1 displayed significant DPPH
      radical-scavenging activity with an IC50 value of 7.9 microM, which is 10-fold
      more potent than that of the positive control, butylated hydroxytoluene.

PMID- 18324824
TI  - Characterization of protein capacity of nanocation exchanger particles as filling
      material for functional magnetic beads for bioseparation purposes.
AB  - In this study we describe the synthesis and characterization of nanocation
      exchanger particles (NCEX) as the functional filling material for magnetic beads.
      Polystyrene NCEX particles were synthesized from styrene via a mini-emulsion
      polymerization. The coupling of cation exchanger groups was done with
      chlorosulfuric acid after the polymerization reaction. The NCEX particles have an
      average diameter of 160-260 nm. Their ion exchange capacity amounts up to 4.58
      mval/g. In an adsorption experiment it was possible to adsorb 192 mg lysozyme/g
      NCEX. Depending on the equilibrium concentration of lysozyme in the bulk solution
      70-85% of the attached protein was desorbed. NCEX particles were used to produce
      magnetic beads with cation exchanger properties. Therefore an innovative
      production process for the synthesis of magnetic beads from different single
      components was used. The produced magnetic beads contained 40 wt % NCEX material
      and showed an ion exchanger capacity of 2 mequiv/g. It was possible to adsorb 75
      mg lysozyme/g magnetic beads with a maximum recovery rate of 95%.

PMID- 18324825
TI  - Ultra scale-down to define and improve the relationship between flocculation and
      disc-stack centrifugation.
AB  - The recovery of intracellular recombinant proteins produced in microbial systems
      typically requires physical, chemical or thermal treatment of the cells post
      harvest to release the product into the broth, followed by removal of the cell
      debris using centrifugation or tangential flow filtration. Often a precipitation
      or flocculation step is introduced to facilitate the liquid-solid separation. Due
      to the complex nature of the cell materials and the unit operations, it is
      difficult to obtain data at laboratory scale that closely reflect the performance
      of these operations on larger scales (pilot or manufacturing). This study uses a
      predictive scale-down model that enables rapid optimization of the operating
      conditions for a flocculation followed with a centrifugation step using only
      small volumes (20 mL) of a high solids ( approximately 20% w/w) E. coli heat
      extract. Results obtained show that, with proper theoretical and experimental
      consideration to account for high cell density, conditions could be found that
      improve the beneficial interaction between flocculation and centrifugation. These
      experiments suggested that adding a higher level of a cationic polymer could
      substantially increase the strength of the flocculated particles produced,
      thereby enhancing overall clarification performance in a large scale centrifuge.
      This was subsequently validated at pilot scale.

PMID- 18324826
TI  - Rapid and efficient selection of yeast displaying a target protein using thermo
      responsive magnetic nanoparticles.
AB  - Magnetic separation provides a relatively quick and easy-to-use method for cell
      isolation and protein purification. We have developed a rapid and efficient
      procedure to isolate yeast cells displaying a target polypeptide, namely, the
      Staphylococcus aureus ZZ domain, which serves as s model for protein interactions
      and can bind immunoglobulin G (IgG). We optimized selection of ZZ-displaying
      yeast cells using thermoresponsive magnetic nanoparticles. A model library was
      prepared by mixing various proportions of target yeast displaying the ZZ domain
      with control cells. Target cells in the model library that bound to the ZZ
      specific binding partner, biotinylated IgG, were selected with biotinylated
      thermoresponsive magnetic nanoparticles using the biotin-avidin sandwich system.
      We determined ZZ expression levels and optimized the concentrations of both
      magnetic nanoparticles and avidin for efficient selection of target cells. After
      optimization, we successfully enriched the target cell population 4700-fold in a
      single round of selection. Moreover, only two rounds of selection were required
      to enrich the target cell population from 0.001% to nearly 100%. Our results
      suggest that magnetic separation will be useful for efficient exploration of
      novel protein-protein interactions and rapid isolation of biomolecules with novel
      functions.

PMID- 18324827
TI  - Applying near-infrared spectroscopy in downstream processing: one calibration for
      multiple clarification processes of fermentation media.
AB  - The use of near-infrared spectroscopy (NIRS) is demonstrated in the first
      downstream processing (DSP) steps of an active pharmaceutical ingredient (API)
      manufacturing process. The first method developed was designed to assess the API
      content in the filtrate stream (aqueous) of a rotary drum vacuum filter. The PLS
      method, built after spectral preprocessing and variable selection, had an
      accuracy of 0.01% (w/w) for an API operational range between 0.20 and 0.45%
      (w/w). The robustness and extrapolation ability of the calibration was proved
      when samples from ultrafiltration and nanofiltration processes, ranging from 0 to
      2% (w/w), were linearly predicted (R2=0.99). The development of a robust
      calibration model is generally a very time-consuming task, and once established
      it is imperative that it can be useful for a long period of time. This work
      demonstrates that NIR procedures, when carefully developed, can be used in
      different process conditions and even in different process steps of similar unit
      operations.

PMID- 18324828
TI  - Design of protein-releasing chitosan channels.
AB  - After traumatic injury to the spinal cord, the neural tissue degenerates,
      resulting in lost function below the site of injury. Promoting axonal
      regeneration after injury remains a challenge; however, guidance channels have
      demonstrated some success when combined with cellular and protein therapies. One
      of the limitations of current guidance channels is the inability to deliver
      therapeutically relevant molecules in situ, within the guidance channel, to
      enhance regeneration. In an effort to provide a system for local and sustained
      drug release, poly(lactide-co-glycolide) (PLGA) microspheres were embedded into
      chitosan guidance channels by a novel spin-coating technique. The method was
      designed to create guidance channels with the appropriate dimensions for
      implantation into the spinal cord, with special attention paid to the wall
      thickness. The release and bioactivity of a model protein, alkaline phosphatase,
      was followed from the channels and compared to those from free-floating
      microspheres over a 90-day period. Since chitosan formulations often require the
      use of acidic solutions, careful attention was paid to redesign the process to
      minimize exposure of PLGA microspheres to acid. This was achieved as demonstrated
      by release and bioactivity data where alkaline phosphatase released from
      chitosan/microsphere channels followed a profile and bioactivity similar to those
      of free floating microspheres.

PMID- 18324829
TI  - Stereocontrolled synthesis of polyfunctionalized cis-decalins from 2
      methoxyphenols: total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta
      angeloyloxyfuranoeremophilane, and (+/-)-3 beta
      methacryloyloxyfuranoeremophilane.
AB  - A four-step stereocontrolled synthesis of polyfunctionalized cis-decalins is
      described, involving oxidation of 2-methoxyphenol, intermolecular Diels-Alder
      reaction, olefination, and Cope rearrangement. Application of this efficient
      strategy to the total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta
      angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane
      was accomplished from creosol and ethyl vinyl ketone via a common intermediate
      21.

PMID- 18324830
TI  - A concise route to beta-Cyclopropyl amino acids utilizing 1,2-dioxines and
      stabilized phosphonate nucleophiles.
AB  - 1,2-Dioxines react with glycine-derived phosphonate nucleophiles via a multistep
      cascade reaction to give beta-cyclopropyl amino acid derivatives in good yield
      with excellent control of the cyclopropane stereocentres. The cyclopropyl ketones
      were oxidized to the corresponding carboxylic esters using Baeyer-Villiger
      conditions. Standard deprotection protocols produced a series of known beta
      cyclopropyl amino acids that are selective and potent agonists or antagonists of
      the metabotropic glutamate receptors in excellent yields.

PMID- 18324831
TI  - Pentakis(trifluoromethyl)phenyl, a sterically crowded and electron-withdrawing
      group: synthesis and acidity of pentakis(trifluoromethyl)benzene, -toluene, 
      phenol, and -aniline.
AB  - A general route to functionalized pentakis(trifluoromethyl)phenyl (C6(CF3)5)
      derivatives, promising building blocks for designing novel stable carbenes,
      radical species, superacids, weakly coordinating anions and other practically and
      theoretically useful species, is presented. This pertrifluoromethylation route
      proceeds via conveniently pregenerated (trifluoromethyl)copper (CF3Cu) species in
      DMF, stabilized by addition of 1,3-dimethyl-2-imidazolidinone (DMI). These
      species react with hexaiodobenzene at ambient temperature to give the potassium
      pentakis(trifluoromethyl)phenoxide along with hexakis(trifluoromethyl)benzene and
      pentakis(trifluoromethyl)benzene in a combined yield of 80%. A possible reaction
      pathway explaining the formation of pentakis(trifluoromethyl)phenoxide is
      proposed. Pentakis(trifluoromethyl)phenol gives rise to easily functionalized
      pentakis(trifluoromethyl)chlorobenzene and pentakis(trifluoromethyl)aniline.
      Pertrifluoromethylation of pentaiodochlorobenzene and pentaiodotoluene allows
      straightforward access to pentakis(trifluoromethyl)chlorobenzene and
      pentakis(trifluoromethyl)toluene, respectively. XRD structures of several
      C6(CF3)5 derivatives were determined and compared with the calculated structures.
      Due to the steric crowding the aromatic rings in all C6(CF3)5 derivatives are
      significantly distorted. The gas-phase acidities (Delta Gacid) and pKa values in
      different solvents (acetonitrile (AN), DMSO, water) for the title compounds and a
      number of related compounds have been measured. The origin of the acidifying
      effect of the C6(CF3)5 group has been explored using the isodesmic reactions
      approach.

PMID- 18324832
TI  - Stereoselective total synthesis of (+)-cardiobutanolide.
AB  - Stereoselective synthesis of styryllactone (+)-cardiobutanolide was accomplished
      in good overall yield from d-(-)-tartaric acid. Key features of the synthesis
      include the elaboration of a gamma-hydroxy butyramide obtained from the
      dimethylamide of tartaric acid, involving a combination of the addition of 1,3
      dithian-2-yllithium and stereoselective reduction.

PMID- 18324833
TI  - Why delta-valerolactone polymerizes and gamma-butyrolactone does not.
AB  - gamma-Butyrolactone, unlike delta-valerolactone, does not polymerize despite a
      strain energy of approximately 8 kcal mol-1 which could be relieved by opening
      the s-cis lactone ester bond to an s-trans ester bond in the polymer. To explain
      this anomaly, we have applied quantum mechanical methods to study the
      thermochemistry involved in the ring-opening reactions of gamma-butyrolactone and
      delta-valerolactone, the conformational preferences of model molecules that mimic
      their corresponding homopolyesters, and the variation of enthalpy associated to
      the polymerizability of such two cyclic lactones. The overall results indicate
      that the lack of polymerizability of gamma-butyrolactone should be attributed to
      the low strain of the ring, which shows much less geometric distortion in the
      ester group than delta-valerolactone, and the notable stability of the coiled
      conformations found in model compounds of poly-4-hydroxybutyrate.

PMID- 18324834
TI  - A theoretical study on the trans-addition intramolecular hydroacylation of 4
      alkynals catalyzed by cationic rhodium complexes.
AB  - The mechanism of the intramolecular hydroacylation reaction of 4-alkynals is
      studied for a 4-pentynal-[Rh(PH2CH2CH2PH2)]+ model system using MP2 calculations.
      The endo-cyclization to form a rhodacyclohexenone intermediate is kinetically
      less favorable than the exo-cyclization to form a rhodacyclopentanone
      intermediate. The kinetic preference toward the endo-cyclization is found to be
      enhanced by complexation of donor ligands (H2CO, NCH, and HCCH). The formation of
      cyclopentenone product proceeds via reductive elimination from one of the two
      rhodacyclohexenone intermediates, whereas the formation of cyclobutanone product
      from the two rhodacyclopentanone intermediates requires high activation energy.
      Addition of an acetylene stabilizes the highly electron-poor rhodacyclopentanone
      intermediate generated from exo-cyclization and leads to an insertion to give [4
      + 2] annulation product, cyclohexenone. The role of a coordinating acetone
      solvent in the formation of cyclopentenone product is also discussed.

PMID- 18324835
TI  - Synthesis and analysis of oligonucleotides containing abasic site analogues.
AB  - DNA damage results in the formation of abasic sites from the formal hydrolysis of
      the glycosidic bond (AP) and several oxidized abasic lesions. Previous studies on
      AP sites revealed that DNA polymerases preferentially incorporated dA opposite
      them in approximately 80% of the replication events in Escherichia coli. These
      results were consistent with the hypothesis that the AP sites are noninstructive
      lesions due to the absence of a Watson-Crick base whose bypass adheres to the "A
      rule." Recent replication studies of the oxidized abasic lesion, 2
      deoxyribonolactone (L), revealed that DNA polymerase(s) does not apply the A-rule
      when bypassing it and incorporates large amounts of dG opposite L. These studies
      suggested that abasic sites such as L do direct polymerases to selectively
      incorporate nucleotides opposite them. However, it was not possible to determine
      the structural basis for this molecular recognition from these experiments. A
      group of oligonucleotides containing analogues of the AP and L lesions were
      synthesized and characterized as probes to gain insight into the structural basis
      for the distinct effect of 2-deoxyribonolactone on replication. These molecules
      will be useful tools for studying replication in cells and in vitro.

PMID- 18324836
TI  - LC-MS/MS for the detection of DNA interstrand cross-links formed by 8
      methoxypsoralen and UVA irradiation in human cells.
AB  - DNA interstrand cross-links (ICLs) are induced by many carcinogens and anitcancer
      drugs. ICL is a covalent linkage of both strands of DNA, preventing DNA strand
      separation during transcription and replication; thus, it is extremely cytotoxic
      in vivo. Psoralen and its derivatives are widely applied for the clinical
      treatment of several skin diseases and cutaneous T cell lymphoma, and they are
      also commonly used as model compounds for the study of ICL. Upon UVA
      photoactivation, 8-methoxypsoralen alkylates both strands of DNA at the 5,6
      double bond of thymidines at the 5'-TpA-3' site, generating monoadducts and ICLs.
      Here we developed a method utilizing HPLC-tandem mass spectrometry, combined with
      nuclease P1 digestion, to assess the formation of ICL in DNA of human skin
      melanoma cells exposed to 500 ng/mL 8-methoxypsoralen and UVA irradiation. We
      were able to quantify ICL, in the form of tetranucleotide, at the level of 1
      lesion/10(6) unmodified nucleobases using a low-microgram quantity of DNA. In
      addition, our results revealed that the formation of ICL increased linearly with
      the UVA dose. The yield of ICL increased by 15-fold from 4.5 to 76 lesions/10(6)
      nucleotides when the UV dose was increased from 0.5 to 5 J/cm2. This is the first
      report of an LC-MS assay for the quantification of DNA interstrand cross-links.
      The specificity and accuracy of this high-throughput approach are advantageous
      over other methods for the detection of ICLs formed in vitro and in vivo.

PMID- 18324837
TI  - Electrochemical, photoelectrochemical, and piezoelectric analysis of tyrosinase
      activity by functionalized nanoparticles.
AB  - The electrochemical and photoelectrochemical detection of tyrosinase (TR)
      activity (an indicative marker for melanoma cancer cells) is reported, using Pt
      nanoparticles (NPs) or CdS NPs as electrocatalytic labels or photoelectrochemical
      reporter units. The Pt NPs or CdS NPs are modified with a tyrosine methyl ester,
      (1), capping layer. Oxidation of the capping layer by TR/O2 yields the respective
      L-DOPA and dopaquinone products. The reduction of the resulting mixture of
      products with citric acid yields the L-DOPA derivative,(3), as a single product.
      The association of the (3)-functionalized Pt NPs or CdS NPs to a boronic acid
      monolayer-modified electrode enables the electrochemical transduction of TR
      activity by the Pt-NPs-electrocatalyzed reduction of H2O2 or the
      photoelectrochemical transduction of TR activity by the generation of
      photocurrents in the presence of triethanolamine as a sacrificial electron donor.
      The detection limits for analyzing TR corresponds to 1 U and 0.1 U by the
      electrochemical and photoelectrochemical methods, respectively. The association
      of the Pt NPs or CdS NPs to the functionalized monolayer electrode is followed by
      quartz crystal microbalance measurements.

PMID- 18324838
TI  - Quantitation from Tafel analysis in solid-state voltammetry. Application to the
      study of cobalt and copper pigments in severely damaged frescoes.
AB  - A novel method, using Tafel plots, for quantifying electroactive species in solid
      materials when their voltammetric signals are strongly overlapped is described.
      This is applied to the analysis of submicrosamples from the highly damaged
      frescoes painted by Palomino (1707) in the ceiling vault of the Sant Joan del
      Mercat church in Valencia, Spain. These paintings, which were fired in 1936,
      contained cobalt smalt plus azurite mixtures, this last being altered to tenorite
      (CuO). The reported method provides a quantitation of the cobalt smalt/azurite,
      tenorite/(azurite + smalt) relationships in samples, thus providing direct
      information on pigment dosage (smalt/azurite ratio) in pristine paintings, extent
      of alteration, and temperature experienced by the frescoes during the gunfire
      episode. Distinction between Palomino paintings and other painters was clearly
      obtained due to the presence of malachite in these last.

PMID- 18324839
TI  - ssDNA aptamer-based surface plasmon resonance biosensor for the detection of
      retinol binding protein 4 for the early diagnosis of type 2 diabetes.
AB  - Retinol binding protein 4 (RBP4) is a useful biomarker in the diagnosis of type 2
      diabetes since its level in the serum is higher in insulin-resistant states.
      Accurate measurement of the serum RBP4 levels is hampered by conventional
      immunologic methods, such as enzyme-linked immunosorbent assay (ELISA). In this
      study, therefore, we have developed an aptamer-based surface plasmon resonance
      (SPR) biosensor that can be used to sense for RBP4 in serum samples. A single
      stranded DNA (ssDNA) aptamer that showed high affinity (Kd = 0.2 +/- 0.03 microM)
      and specificity to RBP4 was selected. This RBP4-specific aptamer was immobilized
      on a gold chip and used in a label-free RBP4 detection using SPR. Analysis of
      RBP4 in artificial serum using SPR was compared with ELISA and Western blot
      analysis. Our results indicated that the RBP4-specific aptamer-based SPR
      biosensor gave better dose-dependent responses and was more sensitive than ELISA
      assays. As such, this RBP4 aptamer-based SPR biosensor can be potentially used to
      monitor the RBP4 levels within the serum as an indicator of type 2 diabetes.

PMID- 18324840
TI  - Minimizing nonspecific cellular binding of quantum dots with hydroxyl-derivatized
      surface coatings.
AB  - Quantum-dot (QD) nanocrystals are promising fluorescent probes for multiplexed
      staining assays in biological applications. However, nonspecific QD binding to
      cellular membranes and proteins remains a limiting factor in detection
      sensitivity and specificity. Here we report a new class of hydroxyl (-OH)-coated
      QDs for minimizing nonspecific cellular binding and for overcoming the bulky size
      problems encountered with previous surface coatings. The hydroxylated QDs are
      prepared from carboxylated (-COOH) dots via a hydroxylation and cross-linking
      process. With a compact hydrodynamic size of 13-14 nm (diameter), they are highly
      fluorescent (>60% quantum yields) and stable under both basic and acidic
      conditions. By using human cancer cells, we have evaluated their superior
      nonspecific binding properties against that of carboxylated, protein-coated, and
      poly(ethylene glycol) (PEG)-coated QDs. Quantitative cellular staining data
      indicate that the hydroxylated QDs result in a dramatic 140-fold reduction in
      nonspecific binding relative to that of carboxylated dots and a still significant
      10-20-fold reduction relative to that of PEG- and protein-coated dots.

PMID- 18324841
TI  - Hollow silica nanocontainers as drug delivery vehicles.
AB  - Novel hollow silica nanoparticles (HSNPs) for drug delivery vehicles were
      synthesized using silica-coated magnetic assemblies, which are composed of a
      number of Fe(3)O(4) nanocrystals, as templates. The core cavity was obtained by
      removal of Fe(3)O(4) phase with hydrochloric acid and subsequent calcination at a
      high temperature. HSNPs were modified by amine in order to introduce positive
      surface charge and further PEGylated for increased solubility in aqueous medium.
      Doxorubicin as a model drug was loaded into the HSNPs, and notable sustained drug
      release from HSNPs was demonstrated.

PMID- 18324842
TI  - Thermosensitive pickering emulsion stabilized by poly(N-isopropylacrylamide)
      carrying particles.
AB  - Poly(N-isopropylacrylamide) (PNIPAM)-carrying particles were characterized as
      thermosensitive Pickering emulsifiers. Emulsions were prepared from various oils,
      such as heptane, hexadecane, trichloroethylene, and toluene, with PNIPAM-carrying
      particles. PNIPAM-carrying particles preferentially formed oil-in-water (O/W)
      type emulsions with a variety of oils. All the emulsions stabilized by PNIPAM
      carrying particles were stable for more than 3 months as long as they were stored
      at room temperature. However, when the emulsions were heated from room
      temperature to 40 degrees C, at which point the PNIPAM layer caused a coil-to
      globule transition, phase separation occurred. Thus, by using thermosensitive
      PNIPAM-carrying particles as emulsifiers, the stability of the Pickering
      emulsions could be controlled by a slight change in temperature.

PMID- 18324843
TI  - Quantifying blood platelet morphological changes by dissipation factor monitoring
      in multilayer shells.
AB  - The ability of electrostatically driven layer-by-layer (LbL) assembly to adapt to
      the morphological features of a template was explored. Subtle cytoskeletal
      changes in blood platelets became traceable through energy dissipation monitoring
      in multilayered shells using microgravimetric measurements. This LbL coating was
      sequentially deposited on protein-modified chips onto which platelets were
      adhered. In addition to consequently improving the signal sensitivity, the LbL
      shell acted in synergy with the cell, allowing the determination and
      quantification of cytoskeletal changes induced by the specific cell adhesion to
      the protein-modified chip surface used with a quartz crystal microbalance with
      dissipation. The difference in cell morphology, as a result of the optimization
      of specific interactions between the protein layer and cell membrane integrins
      induced viscoelastic changes in the polyelectrolyte shell, thereby providing
      quantitative data on platelet conformational changes upon their adhesion to
      protein-modified chip surface.

PMID- 18324844
TI  - Explicit hydrogen molecular dynamics simulations of hexane deposited onto
      graphite at various coverages.
AB  - We present results of molecular dynamics (MD) computer simulations of hexane
      (C6H14) adlayers physisorbed onto a graphite substrate for coverages in the range
      0.5 < or = rho < or = 1 monolayers. The hexane molecules are simulated with
      explicit hydrogens, and the graphite substrate is modeled as an all-atom
      structure having six graphene layers. At coverages above about rho congruent with
      0.9 the low-temperature herringbone solid loses its orientational order at T(1) =
      140 +/- 3 K. At rho = 0.878, the system presents vacancy patches and T(1)
      decreases to ca. 100 K. As coverage decreases further, the vacancy patches become
      larger and by rho = 0.614 the solid is a connected network of randomly oriented
      islands and there is no global herringbone order-disorder transition. In all
      cases we observe a weak nematic mespohase. The melting temperature for our
      explicit-hydrogen model is T(2) = 160 +/- 3 K and falls to ca. 145 K by rho =
      0.614 (somewhat lower than seen in experiment). The dynamics seen in the fully
      atomistic model agree well with experiment, as the molecules remain overall flat
      on the substrate in the solid phase and do not show anomalous tilting behavior at
      any phase transition observed in earlier simulations in the unified atom (UA)
      approximation. Energetics and structural parameters also are more reasonable and,
      collectively, the results from the simulations in this work demonstrate that the
      explicit-hydrogen model of hexane is substantially more realistic than the UA
      approximation.

PMID- 18324845
TI  - Structural details of cellulose nanocrystals/polyelectrolytes multilayers probed
      by neutron reflectivity and AFM.
AB  - Neutron reflectivity measurements and AFM observations were used as complementary
      techniques to investigate multilayered films consisting of alternating sheets of
      rigid cellulose nanocrystals and flexible poly(allylamine hydrochloride) (PAH)
      prepared by the layer-by-layer assembly technique. Both techniques showed that
      smooth films with a high load of cellulose could be obtained. After deposition,
      the cellulose component occurred as a double layer with different densities: 50%
      and 25% for the lower and upper layer, respectively. A linear growth of the
      multilayer and the presence of a Bragg peak on neutron reflectivity curves
      indicated the formation of a well-ordered structure resulting from entropy-driven
      assembly and smoothening effect of the flexible PAH macromolecules. The possible
      alignment of the nanocrystals when anisotropic suspensions were used is also
      shown and opens the route to an improved control of the architecture of these
      multilayers.

PMID- 18324846
TI  - Electroless gold island thin films: photoluminescence and thermal transformation
      to nanoparticle ensembles.
AB  - Electroless gold island thin films are formed by galvanic replacement of silver
      reduced onto a tin-sensitized silica surface. A novel approach to create
      nanoparticle ensembles with tunable particle dimensions, densities, and
      distributions by thermal transformation of these electroless gold island thin
      films is presented. Deposition time is adjusted to produce monomodal ensembles of
      nanoparticles from 9.5 +/- 4.0 to 266 +/- 22 nm at densities from 2.6 x 1011 to
      4.3 x 108 particles cm-2. Scanning electron microscopy and atomic force
      microscopy reveal electroless gold island film structures as well as nanoparticle
      dimensions, densities, and distributions obtained by watershed analysis.
      Transmission UV-vis spectroscopy reveals photoluminescent features that suggest
      ultrathin EL films may be smoother than sputtered Au films. X-ray diffraction
      shows Au films have predominantly (111) orientation.

PMID- 18324847
TI  - Three-dimensional Pt-coated Au nanoparticle arrays: applications for
      electrocatalysis and surface-enhanced Raman scattering.
AB  - This study demonstrates a novel approach to synthesis methods for core-shell
      nanoparticle assembly using nanoparticle trapping at an interface and subsequent
      transfer onto a substrate for electrochemical ultrathin layer coating. The
      transferred nanoparticle array can have a tunable surface area depending on the
      number of transferred layers. Subsequently coating the surface with Pt-group
      metals that behave as an ultrathin film provides electrocatalytic activities with
      respect to a variety of chemical reactions, depending on the properties of the
      selected coating materials. The transferred 3D Au nanoparticle arrays act as a
      high-surface-area platform for the diversity of overlayer materials. The
      resulting 3D core-shell nanoparticle films could be utilized as a highly active
      electrocatalysis and Raman scattering substrate. The approach provides a
      versatile and convenient synthesis route to new nanoporous material with
      tailorable pore structure and material properties through bottom-up assembly.

PMID- 18324848
TI  - Contribution of molecular pathways in the micellar solubilization of monodisperse
      emulsion droplets.
AB  - It is often proposed that oil solubilization in anionic and nonionic micelles
      proceeds by different mechanisms, with diffusion of the oil molecule thought to
      control the former, and the latter interfacially controlled. In order to
      investigate this hypothesis, the effect of aqueous phase viscosity, salt, and
      surfactant concentration during the solubilization process was studied. The
      progressive decrease in average droplet size of nearly monodisperse emulsions
      during solubilization in SDS or Tween 20 micellar solutions was monitored by
      light scattering, and the change in turbidity was measured by UV-vis
      spectrophotometer. The solubilization rates were analyzed using a population
      balance approach to calculate the mass transfer coefficients. Increasing the
      aqueous viscosity by adding sucrose reduced the mass transfer coefficients of n
      tetradecane and n-dodecane but had a smaller effect on n-hexadecane. The strong
      dependence of the solubilization rate for the shorter chain length alkanes on
      aqueous viscosity supported a mechanism in which the oil undergoes molecular
      diffusion before being taken up by micelles. The dependence of the solubilization
      kinetics on surfactant concentration appeared consistent with this mechanism but
      yielded a slower micellar uptake rate than previously predicted theoretically. As
      the solute chain length increased in nonionic surfactant solutions, an
      interfacial mechanism mediated by micelles appeared to contribute substantially
      to the overall rate. Addition of salt only slightly increased the solubilization
      rate of n-hexadecane in SDS solutions and, thus, indicated a weak role of
      electrostatic interactions for ionic surfactants on the overall mechanism.

PMID- 18324849
TI  - Tunable synergism/antagonism in a mixed nonionic/anionic surfactant layer at the
      solid/liquid interface.
AB  - The use of mixed surfactants for modification of solid surfaces is important for
      many applications, since beneficial synergism often occurs depending on the
      surfactant type and mixing conditions. Systematical information on the properties
      of surfactant mixtures at the solid/liquid interface can be helpful for
      optimizing the interactions between the surfactants and then their corresponding
      performance. In this work, a nonionic/anionic surfactant combination, n-dodecyl
      beta-d-maltoside (DM) and sodium dodecyl sulfonate (SDS), was selected for the
      study of adsorption on an oxide solid, alumina. Interestingly, the mixture of the
      two surfactants with opposite pH-dependence of adsorption on alumina exhibits
      some unique synergistic or antagonistic features that were found to be tunable in
      the region of pH 4-10. In addition, the DM/SDS molar ratio in the adsorbed layer
      was found to decrease with concentration in the saturated region at all the pH
      and mixing ratios tested. The decrease is attributed to the monomer concentration
      changes in solution due to the difference in surface activities of the two
      surfactants. The tunable features of this mixture at the solid/liquid interface
      provide a way to optimize the properties by changing the mixing conditions. This
      can be valuable in many applications, such as enhanced oil recovery, flotation,
      and solubilization.

PMID- 18324850
TI  - Diffusing wave spectroscopy study of the colloidal interactions occurring between
      casein micelles and emulsion droplets: comparison to hard-sphere behavior.
AB  - Understanding the underlying processes that govern interparticle interactions in
      colloidal systems is fundamental to predicting changes in their bulk properties.
      In this paper we discuss the colloidal behavior of casein micelles and protein
      stabilized fat globules individually and in a mixture. The colloidal interactions
      were observed by transmission diffusing wave spectroscopy. The turbidity
      parameter, l*, and the diffusion coefficients of the samples studied were
      measured experimentally and compared to the theoretically calculated parameters
      for a hard-sphere system. The light scattering properties of casein micelles
      (volume fraction phi = 0.1-0.2) dispersed in milk permeate showed no deviation
      from the theoretically predicted model. Whey protein isolate (WPI)-stabilized
      emulsions (phi = 0.025-0.1) prepared either in milk permeate or in 5 mM imidazole
      buffer at pH 6.8 showed a behavior identical to that of the hard-sphere model.
      Similarly to the WPI-stabilized fat globules, the sodium caseinate (NaCas)
      stabilized emulsions (phi = 0.025-0.1) prepared in milk permeate also showed
      resemblance to the theory. In contrast, NaCas-stabilized emulsions prepared in 5
      mM imidazole buffer exhibited some discrepancy from the theoretically calculated
      parameters. The deviation from theory is attributed to the enhanced steric
      stabilization properties of these droplets in a low ionic strength environment.
      When recombined milks made from concentrated milk and WPI- and NaCas-stabilized
      droplets prepared in permeate (phi = 0.125-0.2) were studied, the experimental
      data showed a significant deviation from the theoretical behavior of a hard
      sphere model due to mixing of two different species.

PMID- 18324851
TI  - Enzymatic kinetics of cellulose hydrolysis: a QCM-D study.
AB  - The interactions between films of cellulose and cellulase enzymes were monitored
      using a quartz crystal microbalance (QCM). Real-time measurements of the coupled
      contributions of enzyme binding and hydrolytic reactions were fitted to a kinetic
      model that described closely significant cellulase activities. The proposed model
      combines simple Boltzmann sigmoidal and 1 - exp expressions. The obtained
      kinetics parameters were proven to be useful to discriminate the effects of
      incubation variables and also to perform enzyme screening. Furthermore, it is
      proposed that the energy dissipation of a film subject to enzymatic hydrolysis
      brings to light its structural changes. Overall, it is demonstrated that the
      variations registered in QCM frequency and dissipation of the film are indicative
      of mass and morphological transformations due to enzyme activities; these include
      binding phenomena, progressive degradation of the cellulose film, existence of
      residual, recalcitrant cellulose fragments, and the occurrence of other less
      apparent changes throughout the course of incubation.

PMID- 18324852
TI  - Biomimetic fabrication of lotus-leaf-like structured polyaniline film with stable
      superhydrophobic and conductive properties.
AB  - Superhydrophobic surfaces were successfully prepared on Ti/Si substrates via the
      fabrication of conductive polyaniline (PANI) nanowire film. The PANI nanowire
      film was synthesized by electrodeposition of aniline into the pores of an anodic
      aluminum oxide (AAO) template on Ti/Si substrate followed by the removal of the
      template. The surface showed conductivity and superhydrophobicity, even in many
      corrosive solutions, such as acidic or basic solutions over a wide pH range.
      Field emission scanning electron microscopy (FE-SEM) demonstrated that the binary
      geometric structures at micro- and nanometer scale bestowed the prerequisite
      roughness on the surfaces. The chemical surface modification made the PANI
      nanowire film superhydrophobic. The results demonstrated that the PANI nanowire
      film will have good potential applications in the preparation of conductive
      superhydrophobic surfaces.

PMID- 18324854
TI  - Surface-enhanced infrared absorption spectroscopic studies of adsorbed nitrate,
      nitric oxide, and related compounds 1: Reduction of adsorbed NO on a platinum
      electrode.
AB  - Surface-enhanced infrared absorption spectroscopy (SEIRA) was used to examine the
      adsorption state of nitrogen monoxide (nitric oxide, NO) and the reduction of the
      adsorbed species. The SEIRA spectra gave two distinct bands at 1723-1733 and 1575
      1607 cm-1 with an additional weak band at 1656-1676 cm-1 at 0.20 V, the
      frequencies of which are slightly dependent on the surface coverage. The former
      two bands are attributed to the on-top and bridged NO, respectively. While the on
      top NO stably remained on the surface in the potential range of 0.05 -0.60 V, the
      bridged NO decreased in its intensity with increasing electrode potential. The
      reduction of the adsorbed NO obeys first-order kinetics with respect to the
      adsorbed NO. The rate constants are 2.24 +/- 0.03 and 0.24 +/- 0.09 s-1 at -0.10
      V for the on-top and bridged NO, respectively. Tafel slopes obtained from the
      potential dependence of the rate constant indicate that the rate-determining step
      is the first electron-transfer process.

PMID- 18324853
TI  - Gold nanoparticle sensor for homocysteine thiolactone-induced protein
      modification.
AB  - Homocysteine thiolactone-induced protein modification (HTPM) is a unique post
      translational protein modification that is recognized as an emergent biomarker
      for cardiovascular disease. HTPM involves the site-specific acylation of proteins
      at lysine residues by homocysteine thiolactone (HTL) to produce protein
      homocystamide, which has been found at elevated levels in patients with coronary
      heart disease. Herein, we report the development of a novel gold nanoparticle
      (GNP) biochemical sensor for detection of protein homocystamide in an in vitro
      serum protein-based model system. Human serum albumin (HSA) and human sera were
      subjected to HTPM in vitro to produce HSA-homocystamide or serum protein
      homocystamide, respectively, which was subsequently treated with citrate-capped
      GNPs. This GNP sensor typically provided instantaneous visual confirmation of
      HTPM in the protein model systems. Transmission electron microscopy images of the
      GNPs in the presence of HSA-homocystamide suggest that modification-directed
      nanoparticle assembly is the mechanism by which the biochemical sensor produces a
      colorimetric signal. The resultant nanoparticle-protein assembly exhibited
      excellent thermal and dilutional stability, which is expected for a system
      stabilized by chemisorption and intermolecular disulfide bonding. The sensor
      typically provided a linear response for modified human sera concentrations
      greater than approximately 5 mg/mL. The calculated limit of detection and
      calibration sensitivity for the method in human sera were 5.2 mg/mL and 13.6 AU .
      (microg/mL)-1, respectively.

PMID- 18324855
TI  - The diamond/aqueous electrolyte interface: an impedance investigation.
AB  - We have investigated the electrochemical interface between diamond electrodes and
      aqueous electrolytes using electrochemical techniques such as cyclic voltammetry
      and ac impedance spectroscopy. High-quality CVD-grown boron-doped polycrystalline
      diamond electrodes and IIa single crystalline natural diamond electrodes have
      been used in this study. In the case of hydrogen-terminated diamond electrodes,
      the electrochemical interface is dominated by the electrochemical double layer.
      Frequency-dependent impedance spectroscopy reveals a potential regime in which
      the contribution of ion adsorption becomes relevant. We have conducted
      experiments to evaluate the effect of pH and ionic strength on the double layer.
      Our results suggest that only ions resulting from water auto-dissociation, i.e.,
      hydroxide and hydronium ions, are responsible for ion adsorption and, thus, able
      to modify the charge at the double layer. In contrast, no effect of the
      adsorption of several dissolved ions (such as Na+, K+, Cl-) has been observed On
      the basis of the electrochemical characterization of H-terminated diamond
      surfaces, we also discuss the phenomenon of the surface conductivity in diamond,
      as well as the pH sensitivity of the diamond surface. The influence of the O2/OH-
      and H2/H3O+ redox couples on the origin of the surface conductivity is discussed.

PMID- 18324856
TI  - Surface-enhanced infrared absorption spectroscopic studies of adsorbed nitrate,
      nitric oxide, and related compounds 2: Nitrate ion adsorption at a platinum
      electrode.
AB  - The adsorbed species formed from the nitrate ion were examined using surface
      enhanced infrared absorption spectroscopy (SEIRAS). The main band was observed at
      1547-1568 cm-1 at 0.2 V in 0.01 M NaNO3 + 0.1 M HClO4. Although this band is
      close to that assigned to the adsorbed NO in the literature, it is assigned to
      the N=O stretching vibration of the chelating bidentate form of nitrate for the
      following reasons. (i) Nitrate gives a single band, while NO has three bands
      independent of the coverage. (ii) The band intensity remained constant in the
      potential range from 0.1 to 0.6 V, while that of the bridged NO at around 1600 cm
      1 decreased in this range. (iii) The rate constants for the reduction and/or
      desorption at negative potentials are about 3 times higher than those of the
      bridged NO. (iv) The adsorbed species from nitrate is replaced with CO more
      easily than the bridged NO.

PMID- 18324857
TI  - Inclusion complex of n-octyl beta-D-glucopyranoside and alpha-cyclodextrin in
      aqueous solutions: thermodynamic and structural characterization.
AB  - Complex formation between octyl beta-D-glucopyranoside (OG) and alpha
      cyclodextrin (alphaCD) was investigated on the basis of three highly accurate and
      appropriate experimental techniques. First, surface tension measurements showed
      that alphaCD directly acts on the surfactant monomers in the aqueous phase,
      leading to progressive depletion of the air-water interface with increasing
      cyclodextrin contents. Significant shift of OG critical micelle concentration
      (cmc) was consequently observed: the higher alphaCD concentration, the higher the
      cmc value. Experiments performed at surfactant and cyclodextrin concentrations in
      the Gibbs regime of surface tension versus OG content were performed on one hand
      to establish Job's plot that showed 1:1 stoichiometry of the OG-alphaCD complex
      and on the other hand to calculate the association constant found equal to (1.85
      +/- 0.35) x 10(3) L mol(-1). An inclusion process of the surfactant alkyl residue
      within the cyclodextrin cavity was confirmed by one-dimensional (1)H NMR, and the
      structure of the mixed assembly was extensively characterized by two-dimensional
      NOESY (1)H NMR. OG penetrates alphaCD so that its hydrocarbon chain is embedded
      inside the cyclodextrin cavity, and its polar head as well as the alpha-methylene
      group emerges outside the alphaCD secondary face. Solubility behavior of the OG
      alphaCD complex in a wide range of host-guest ratios and concentrations was
      finally examined by turbidity recording and optical microscopy. At very low free
      cyclodextrin levels in the solution, the complex presented high solubility
      behavior up to more than 70 mM. By increasing nonassociated alphaCD in the
      mixture, propensity of the cyclodextrin molecules to crystallize was observed at
      concentrations far below the 100 mM aqueous solubility of the pure cyclodextrin.
      The hexagonal shape of the crystals seen in the optical microscopy images
      suggested they were, partially at least, composed of the solid complex.

PMID- 18324858
TI  - Surfactant-assisted shape evolution of thermally synthesized TiO2 nanocrystals
      and their applications to efficient photoelectrodes.
AB  - TiO2 nanocrystals were synthesized via a two-phase thermal process, and the shape
      of the nanocrystals was controlled from nanospheres to nanorods by the ratio of
      two surfactants. The shape control of nanocrystals was ascribed to the selective
      adsorption of the two surfactants. The shape of TiO2 nanocrystals influenced the
      photocatalytic performances of the photoelectrodes through two compromising
      factors: the relative surface area and the electron transport. The photoelectrode
      composed of nanorods showed a slower charge recombination rate, while it showed a
      smaller specific surface area, compared to nanospheres. As a result, the
      photoelectrodes showed the optimal photocatalytic performance when the
      nanospheres and the nanorods were mixed.

PMID- 18324859
TI  - Co-ion and ion competition effects: ion distributions close to a hydrophobic
      solid surface in mixed electrolyte solutions.
AB  - We consider within a modified Poisson-Boltzmann theory an electrolyte, with
      different mixtures of NaCl and NaI, near uncharged and charged solid hydrophobic
      surfaces. The parametrized potentials of mean force acting on Na+, Cl-, and I-
      near an uncharged self-assembled monolayer were deduced from molecular
      simulations with polarizable force fields. We study what happens when the surface
      presents negative charges. At moderately charged surfaces, we observe strong co
      ion adsorption and clear specific ion effects at biological concentrations. At
      high surface charge densities, the co-ions are pushed away from the interface. We
      predict that Cl- ions can also be excluded from the surface by increasing the
      concentration of NaI. This ion competition effect (I- versus Cl-) may be relevant
      for ion-specific partitioning in multiphase systems where polarizable ions
      accumulate in phases with large surface areas.

PMID- 18324860
TI  - Superhydrophobic surfaces formed using layer-by-layer self-assembly with aminated
      multiwall carbon nanotubes.
AB  - A convenient and simple route to functionalized multiwall carbon nanotubes
      (MWNTs) using the reaction of the amine (NH) groups of polyethyleneimine (PEI)
      with MWNTs in N,N-dimethylformamide (DMF) at 50 degrees C is described. The
      product functionalized MWNTs (MWNT-NH-PEI) contain 6-8% by weight PEI based on
      elemental analysis, thermal gravimetric analysis, and titration. The products
      form stable emulsions in water below pH 9 and can be derivatized to form
      alkylated MWNTs that are dispersible in organic media. Such MWNT-NH-PEI
      nanoparticles can also be used in covalent or ionic layer-by-layer assembly to
      form nanocomposite thin films on functionalized polyethylene (PE) films and
      powders. Such nanocomposite films were analyzed by contact angle analysis, atomic
      force microscopy (AFM), and confocal Raman microscopy. These analyses show that
      these superhydrophilic surfaces have micro/nanoroughness with a roughly uniform
      distribution of MWNT nanoparticles. Superhydrophobic PE films can be formed
      either from ionic layer-by-layer self-assembly of MWNT-NH-PEIs and poly(acrylic
      acid) or from covalent layer-by-layer self-assembly of MWNT-NH-PEIs and Gantrez
      if the final graft is acrylated with a mixed anhydride prepared from ethyl
      chloroformate and octadecanoic acid. The resulting octadecylated surface produced
      by five covalent layer-by-layer deposition steps has a water contact angle of 165
      degrees and a sliding angle of less than 5 degrees. The corresponding surface
      produced by five ionic layer-by-layer deposition steps has a water contact angle
      of 155 degrees but exhibits water pinning. The ionically assembled nanocomposite
      graft is labile under acidic conditions. The covalently assembled graft is more
      chemically robust.

PMID- 18324861
TI  - Thermodynamics of adsorption of imidacloprid at constant charge hydrophobic
      surfaces: physicochemical aspects of bioenvironmental activity.
AB  - Adsorption of the insecticide 1-(6-chloro-3-pyridylmethyl)-N-nitroimidazolidin-2
      ylideneamine (Imidacloprid) on the hanging mercury drop electrode (HMDE) surface
      was studied by temperature-dependent stripping voltammetry (TD-SV). At near
      physiological pH, under reducing conditions, the Gibbs free energy of adsorption,
      DeltaGADS, shows two distinct temperature-dependent regimes. (a) At 0 degrees < T
      < 10 degrees C a temperature-independent mechanism occurs with a constant
      DeltaGADS = -40.5 kJ/mol, resulting in strong chemisorption at high surface
      coverage. For T < 10 degrees C a considerable enthalpy gain is estimated, and
      this represents the driving force for the adsorption of Imidacloprid onto the
      electrode surface. (b) At T > 10 degrees C a temperature-dependent mechanism is
      operative with DeltaGADS/DeltaT = -91.4 J/K mol, resulting in a rapid weakening
      of adsorption and low surface coverage. On the basis of the present findings we
      suggest that the strong chemisorption at T < 10 degrees C at physiological pH
      under reducing conditions is related to the high specific insecticide activity of
      Imidacloprid in cool-blooded insects as contrasted to its low efficiency in warm
      blooded organisms.

PMID- 18324862
TI  - Electrochemically controlled growth and positioning of suspended collagen
      membranes.
AB  - Two independently recognized in vitro polymer aggregation variables, electric
      field and pH, can be used in concert to produce suspended membranes from
      solutions of type I collagen monomers, without need of a supporting substrate. A
      collagen network film can form at the alkaline-acidic pH interface created during
      the normal course of water electrolysis with parallel plate electrodes, and the
      anchoring location can be controlled by adjusting the bulk electrolyte pH.
      Electrosynthesized films remain intact upon drying and rehydration and function
      as ion-separation membranes even in submillimeter channels. This approach could
      benefit lab-on-a-chip technologies for the rational placement of membranes in
      microfluidic devices.

PMID- 18324863
TI  - Light-induced aggregation of colloidal gold nanoparticles capped by thymine
      derivatives.
AB  - The colloid stability of thymine-coated gold nanoparticles under light
      irradiation as a function of particle size, surface charge, and exposure time was
      investigated in alkaline, aqueous solutions as well as in a 0.5 vol % of DMF in
      H(2)O mixture. With increasing exposure to light irradiation at 280 nm, more and
      more particles coagulated. Light-induced aggregation of colloidal gold
      nanoparticles was attributed to reorientation of thymine terminal groups tethered
      on gold particle surfaces. A smaller particle size and negatively charged surface
      reduced the rate of photodimerization or even inhibited the photoreaction. UV-vis
      and FTIR spectroscopy confirmed the photodimerization of terminal thymine
      molecules under 280 nm light irradiation. The reaction kinetics of thymine
      photodimerization appears to be a combination of first-order reactions, each
      having different rates, reflecting the inhomogeneity and high curvature of the
      gold nanoparticle surfaces.

PMID- 18324864
TI  - Release and transfer of polystyrene dewetting pattern by hydration force.
AB  - We studied the release and transfer of polystyrene (PS) microdots on mica. The PS
      dots were released from the mica in water. The release was affected by the
      density of K(+) ions on the mica surface, which was controlled by pretreatment
      with K(2)CO(3) solutions. The release of PS dots became dominant at the
      concentrations above [K(+)]crit = 1 x 10(-4) M in the K(2)CO(3) solution. In this
      concentration region, repulsive forces appeared as a result of the hydration of
      K(+) ions on the mica (J. Colloid Interface Sci. 1981, 83, 531). This result
      suggests that the repulsive hydration force causes the release of the PS dots.
      Followed by the release process, we successfully demonstrated the transfer of the
      array of PS dots from the mica to another substrate.

PMID- 18324865
TI  - Layer-by-layer deposited multilayer films of oligo(pyrenebutyric acid) and a
      perylene diimide derivative: structure and photovoltaic properties.
AB  - Multilayer films of oligo(pyrenebutyric acid) (OPB) and N,N'-bis(N,N
      dimethylaminopropylaminopropyl)-3,4,9,10-perylenediimide (BDMAPAP-PDI) were
      successfully fabricated by layer-by-layer deposition. Multilayer growth was
      monitored by ultraviolet-visible (UV-vis) spectroscopy, fluorescence
      spectroscopy, ellipsometry, and atomic force microscopy (AFM). It was found that
      extraction was scarcely observed although both components (OPB and BDMAPAP-PDI)
      have low molecular weights and both electrostatic interactions and pi-pi stacking
      contributed to the multilayer deposition. The multilayers exhibit a rapid
      photocurrent response, and excitations of both OPB and BDMAPAP-PDI can lead to
      the effective charge dissociation. The incident photon to current conversion
      efficiency (IPCE) of the composite film with 5 bilayers was measured to be 1.29%
      at the absorption peak of BDMAPAP-PDI. Fluorescence quenching and photovoltaic
      conversion studies indicated that strong photoinduced charge transfer
      interactions occurred at the area of OPB/BDMAPAP-PDI heterojunction in the films,
      which strongly enhanced the photoresponse of the multilayer films.

PMID- 18324866
TI  - Nematic pancakes revisited.
AB  - The spontaneous spreading of the 5CB nematic liquid crystal on solid substrates
      has been extensively studied in the last years both at the microscopic(1-4) and
      macroscopic(5-6) scales. The remarkable feature at the microscopic scale is the
      presence of a discontinuity in the thickness profile of the films. On the other
      hand, the spreading dynamics of macroscopic drops is quite specific. The drop
      first spreads like a simple liquid, and then progressively faster, while a
      remarkable bell-shaped profile develops at the bottom.(5-6) How the behaviors at
      the various scales are linked is an open question. Any answer requires
      reconsidering these wetting experiments deeper into the context of nematic films.
      More specifically, the anchoring of molecules at the interfaces(7-8) and the
      competition between nematic elasticity(9) and anchoring(10) must be discussed
      quantitatively. For the thinnest films, the problem proves to be more complex
      than expected and contradictory data are found in the literature. Therefore, we
      decided to complete our previous studies with further experiments using another
      compound of the cyanobiphenyls series, the 6CB in the nematic phase, and also on
      liquid substrates, water and glycerol. These new data confirm that the
      description of the thinnest nematic films is not yet fully understood.

PMID- 18324867
TI  - Covalent attachment of organic monolayers to silicon carbide surfaces.
AB  - This work presents the first alkyl monolayers covalently bound on HF-treated
      silicon carbide surfaces (SiC) through thermal reaction with 1-alkenes. Treatment
      of SiC with diluted aqueous HF solutions removes the native oxide layer (SiO2)
      and provides a reactive hydroxyl-covered surface. Very hydrophobic methyl
      terminated surfaces (water contact angle theta = 107 degrees ) are obtained on
      flat SiC, whereas attachment of omega-functionalized 1-alkenes also yields well
      defined functionalized surfaces. Infrared reflection absorption spectroscopy,
      ellipsometry, and X-ray photoelectron spectroscopy measurements are used to
      characterize the monolayers and show their covalent attachment. The resulting
      surfaces are shown to be extremely stable under harsh acidic conditions (e.g., no
      change in theta after 4 h in 2 M HCl at 90 degrees C), while their stability in
      alkaline conditions (pH = 11, 60 degrees C) also supersedes that of analogous
      monolayers such as those on Au, Si, and SiO2. These results are very promising
      for applications involving functionalized silicon carbide.

PMID- 18324868
TI  - Head group modulated pH-responsive hydrogel of amino acid-based amphiphiles:
      entrapment and release of cytochrome c and vitamin B12.
AB  - The present study describes the rational design and synthesis of amino acid-based
      amphiphilic hydrogelators, which were systemically fine-tuned at the head group
      to develop pH-responsive hydrogels. To understand the basic structural
      requirements of a low molecular weight amphiphilic hydrogelator, 10 analogous
      amphiphiles based on L-phenylalanine and L-tyrosine with structurally related
      head group were synthesized. Among them, three with quaternary ammonium
      substitution at the head group formed transparent hydrogels at room temperature
      while others were unable to gelate water. To establish correlations between the
      head group architecture of the gelators and their supramolecular arrangements, a
      variety of spectroscopic and microscopic techniques were investigated that showed
      that a balance between hydrophilicity and hydrophobicity is required to achieve
      hydrogelation. Interestingly, the gelator with tyrosinate in its head group
      showed remarkable response toward external pH. All hydrogels including the pH
      responsive one were used in the controlled and/or pH-triggered release of
      entrapped (with in hydrogels) vitamin B12 and cytochrome c at different pHs.
      Since the hydrogels were formed at room temperature without heating, this could
      be very important during the entrapment of biomolecules such as proteins because
      of their heat sensitivity. At biological pH (7.4), the release of entrapped
      biomolecules from all three hydrogels was caused by diffusion through the gel
      structure, but at endosomal pH (approximately 5.5) and further lower pH, the
      release rate of biomolecules from the pH-responsive hydrogel with tyrosinate head
      group (pKa approximately equal to 7.2) increased by 9-10-fold compared to that
      observed at physiological pH, because of gel dissolution. Retention of the
      structure and activity of released biomolecule has established the prospect of
      the hydrogel as an efficient drug delivery vehicle.

PMID- 18324869
TI  - Electrolyte-dependent multiparticle motion near electrodes in oscillating
      electric fields.
AB  - The directed assembly of micrometer-scale particles into hexagonal lattices on
      electrodes was probed by subjecting them to electric fields oscillating at 100
      Hz. Solutions of KOH, NaHCO(3), and KCl were used because previous investigations
      of particle pair behavior had shown that an electrolyte-dependent phase angle
      dictates whether two particles aggregate or separate at low frequencies. Here it
      was found that particle ensembles, aggregating or separating, adopt a 2D
      hexagonal lattice in both cases; the difference appears in the particle spacing.
      For electrolytes such as NaHCO(3) and KCl, where two isolated particles
      aggregate, the gap between particle edges is between 1 and 1.5 particle
      diameters; in KOH, where two particles tend to separate, the interparticle
      spacing is several diameters.

PMID- 18324870
TI  - Altering the activity of syringomycin E via the membrane dipole potential.
AB  - The membrane dipole potential is responsible for the modulation of numerous
      biological processes. It was previously shown (Ostroumova, O. S.; Kaulin, Y. A.;
      Gurnev, P. A.; Schagina, L. V. Langmuir 2007, 23, 6889-6892) that variations in
      the dipole potential lead to changes in the channel properties of the antifungal
      lipodepsipeptide syringomycin E (SRE). Here, data are presented demonstrating the
      effect of the membrane dipole potential on the channel-forming activity of SRE. A
      rise in the dipole potential is accompanied by both an increase in the minimum
      SRE concentration required for the detection of single channels at fixed voltage
      and a decrease in the steady-state number of open SRE channels at a given SRE
      concentration and voltage. These alterations are determined by several factors:
      gating charge, connected with translocations of lipid and SRE dipoles during
      channel formation, the bilayer-water solution partitioning of SRE, and the
      chemical work related to conformational changes during channel formation.

PMID- 18324871
TI  - Enhancing the ecological risk assessment process.
AB  - The Ecological Processes and Effects Committee of the US Environmental Protection
      Agency Science Advisory Board conducted a self-initiated study and convened a
      public workshop to characterize the state of the ecological risk assessment
      (ERA), with a view toward advancing the science and application of the process.
      That survey and analysis of ERA in decision making shows that such assessments
      have been most effective when clear management goals were included in the problem
      formulation; translated into information needs; and developed in collaboration
      with decision makers, assessors, scientists, and stakeholders. This process is
      best facilitated when risk managers, risk assessors, and stakeholders are engaged
      in an ongoing dialogue about problem formulation. Identification and
      acknowledgment of uncertainties that have the potential to profoundly affect the
      results and outcome of risk assessments also improves assessment effectiveness.
      Thus we suggest 1) through peer review of ERAs be conducted at the problem
      formulation stage and 2) the predictive power of risk-based decision making be
      expanded to reduce uncertainties through analytical and methodological approaches
      like life cycle analysis. Risk assessment and monitoring programs need better
      integration to reduce uncertainty and to evaluate risk management decision
      outcomes. Postdecision audit programs should be initiated to evaluate the
      environmental outcomes of risk-based decisions. In addition, a process should be
      developed to demonstrate how monitoring data can be used to reduce uncertainties.
      Ecological risk assessments should include the effects of chemical and
      nonchemical stressors at multiple levels of biological organization and spatial
      scale, and the extent and resolution of the pertinent scales and levels of
      organization should be explicitly considered during problem formulation. An
      approach to interpreting lines of evidence and weight of evidence is critically
      needed for complex assessments, and it would be useful to develop case studies
      and/or standards of practice for interpreting lines of evidence. In addition,
      tools for cumulative risk assessment should be developed because contaminants are
      often released into stressed environments.

PMID- 18324872
TI  - Limitations of the current practices used to perform ecological risk assessment.
AB  - The framework for ecological risk assessments has provided a way to analyze
      stressors in the environment. Despite the power of this tool to inform
      environmental management decisions, the practice has not reached its full
      potential. In this paper, limitations of the practice are described under 2
      categories, namely inherent and contrived. Inherent limitations are constraints
      of nature that we need to be aware of as we design and interpret studies.
      Contrived limitations are impediments that have arisen in the practice through
      precedent or policy. The closing portion of this paper provides a series of short
      term and long-term steps that could remove some of the limitations, especially
      the contrived ones, and improve the usefulness of risk assessments.

PMID- 18324873
TI  - Toxicological and public good considerations for the regulation of nanomaterial
      containing medical products.
AB  - Increasing research interest in the new and unusual properties of nanotechnology
      related pharmaceuticals and medical devices has led to international and national
      reviews of safety regulation. Significant considerations emerging here are the
      relative paucity of metrological and toxicological data, as well as the absence
      of adequate funding and standardized approaches for its acquisition. Some areas
      are better researched, such as the toxicity of carbon nanotubes and use of
      engineered nanoparticle titanium and zinc oxides as broad-spectrum ultraviolet
      blocking agents. Such in vitro studies do reveal concerns--for example, related
      to oxidative stress and granuloma formation--but their uncertain clinical
      ramifications may require more integration in preclinical drug discovery of
      research characterizing structure-toxicity relationships and limiting safety
      liabilities. Regulatory considerations for medically related nanoproducts should
      also involve improving cost-effectiveness systems and ensuring that industry
      involvement in standard-setting does not become a means of reducing competition.
      It is also important that nanotechnology policy and regulation encourages new
      models of safe drug discovery and development that are more systematically
      targeted at the global burden of disease.

PMID- 18324874
TI  - The role of early in vivo toxicity testing in drug discovery toxicology.
AB  - The cost impact of late-stage failures of drug candidates has motivated the
      pharmaceutical industry to develop, validate, and implement a more proactive
      testing paradigm, including an emphasis on conducting predictive in vitro and in
      vivo studies earlier. The goal of drug discovery toxicology is not to reduce or
      eliminate attrition, as is often mis-stated as such, but rather to reprioritize
      efforts to shift attrition of future failing molecules upstream in discovery.
      This shift in attrition requires additional studies and investment earlier in the
      candidate evaluation process in order to avoid spending resources on molecules
      with soon-to-be-discovered development-limiting liabilities. While in silico and
      in vitro models will continually be developed and refined, in vivo preclinical
      safety models remain the gold standard for assessing human risk. For in vivo
      testing to influence early discovery effectively, it must: i) require low amounts
      of compound; ii) provide rapid results to drive decision-making and medicinal
      chemistry efforts; and iii) be flexible and provide results relevant to the
      development plan tailored to each target, drug class, and/or indication.

PMID- 18324875
TI  - The safety of dopamine agonists in the treatment of Parkinson's disease.
AB  - Dopamine agonists are highly effective as adjunctive therapy to levodopa in
      advanced Parkinson's disease. These drugs have rapidly gained popularity as a
      monotherapy in the early stages of Parkinson's disease for patients < 65-70 years
      old, because they are about as effective as levodopa, but patients demonstrate a
      lower tendency to develop motor complications. However, dopamine agonists could
      have peripheral and central side effects, which are often the reason for the
      discontinuation of the treatment. This review focuses on the potential negative
      effects related to the use of dopamine agonists in the treatment of Parkinson's
      disease.

PMID- 18324876
TI  - Drug-induced mitochondrial dysfunction in cardiac and skeletal muscle injury.
AB  - BACKGROUND: The list of clinically relevant molecules that affect skeletal and
      cardiac muscle mitochondria is gradually increasing, which strongly suggest that
      mitochondrial toxicity should be an important end point during the design and
      testing of novel pharmaceuticals. OBJECTIVE: The present review intends to
      describe mechanisms by which clinically relevant drugs are known to alter
      mitochondrial function in cardiac and skeletal muscle, which is suggested to be
      involved in the toxicity associated with those drugs. METHODS: Literature
      databases were searched in order to identify clinically relevant drugs with
      associated mitochondrial muscle toxicity. CONCLUSION: Mitochondrial function is
      important in the context of muscle survival, hence, the requirement to identify
      novel mitochondrial targets and develop new therapies to counteract chemical
      induced degeneration of mitochondrial function and muscle performance.

PMID- 18324877
TI  - Drug-induced crystal nephropathy: an update.
AB  - BACKGROUND: Several medications that are insoluble in human urine are known to
      precipitate within the renal tubules. Intratubular precipitation of either
      exogenously administered medications or endogenous crystals (induced by certain
      drugs) can promote chronic and acute kidney injury, termed crystal nephropathy.
      Clinical settings that enhance the risk of drug or endogenous crystal
      precipitation within the kidney tubules include true or effective intravascular
      volume depletion, underlying kidney disease, and certain metabolic disturbances
      that promote changes in urinary pH favoring crystal precipitation. OBJECTIVE:
      Identify and review previously described and recently recognized medications that
      cause crystal nephropathy. METHOD: A literature review was performed, using
      PubMed, Ovid, and Google Scholar, focusing on drugs (sulfadiazine, acyclovir,
      indinavir, triamterene, methotrexate (MTX), orlistat, oral sodium phosphate
      preparation, ciprofloxacin) that cause crystal nephropathy. RESULTS/CONCLUSION:
      Sulfadiazine, acyclovir, indinavir, triamterene, and MTX are known to cause
      crystal nephropathy. Recently, several medications, including orlistat,
      ciprofloxacin, and oral sodium phosphate solution, along with underlying risk
      factors have been described as causing crystal nephropathy.

PMID- 18324878
TI  - Anticancer therapy in patients with porphyrias: evidence today.
AB  - BACKGROUND: Porphyrias are rare diseases, and for these patients every
      administration of drugs may induce an acute attack of porphyria. The list of safe
      compounds allowed in these patients is available for clinicians from specific
      websites cited in the text. OBJECTIVES: However, data concerning anticancer
      therapy in patients with such diseases remain poor. Therefore any publications
      can help clinicians to deal with this very specific group of patients. METHODS:
      In our institution, three patients received docetaxel and hematologic growth
      factors (erythropoietin and GCSF) without unexpected toxicities. Aromatase
      inhibitors (anstrozole and letrozole) were also given in one patient without any
      related problem. CONCLUSION: The present observation adds some useful data for
      the possible treatment of cancer in patients with porphyria.

PMID- 18324879
TI  - The safety of diclofenac for the management and treatment of actinic keratoses.
AB  - BACKGROUND: Actinic keratoses (AKs), defined as carcinoma in situ of squamous
      carcinoma, is usually induced by excessive sun exposure. The efficacy of 3%
      diclofenac in 2.5% hyaluronic acid gel for treatment of AKs has been documented
      in a few studies. OBJECTIVE: Is diclofenac safe and effective for the management
      and treatment of AKs? METHOD: All the papers that were cited in Medline and ISI
      Web of Science are included in this study. RESULTS/CONCLUSION: The use of
      diclofenac is associated with a few side effects, which include pruritus, rashes,
      dry skin, and scaling. These side effects are usually minimal and tolerable;
      therefore, this topical medication is suggested as the first line of treatment
      for AKs.

PMID- 18324880
TI  - The effect of anticholinergic agents on gastro-oesophageal reflux and related
      disorders.
AB  - The most important risk factor of oesophageal adenocarcinoma is gastro
      oesophageal reflux disease. Gastro-oesophageal reflux disease is in itself a
      common disorder, giving bothersome symptoms. In daily clinical practice,
      anticholinergic drugs are believed to increase the risk of gastro-oesophageal
      reflux through effects on the lower oesophageal sphincter. In this review we
      discuss the available literature on the potential association between the use of
      drugs with anticholinergic properties and the risk of gastro-oesophageal reflux
      related disorders.

PMID- 18324882
TI  - Antiepileptic drugs as human teratogens.
AB  - BACKGROUND: There is still uncertainty concerning the risk of fetal malformation
      associated with the intake of various individual antiepileptic drugs in pregnant
      women. OBJECTIVE: To assess the better-quality available evidence concerning the
      fetal hazards from exposure to antiepileptic drug monotherapy during human
      pregnancy. METHOD: Examination of the available English language literature,
      particularly that dealing with individual antiepileptic drugs used in
      monotherapy, in the larger case series with better-quality internal comparison
      data. CONCLUSIONS: There is reasonable evidence that valproate is a significant
      teratogen during therapeutic use in women; the other older antiepileptic drugs
      (phenobarbitone, phenytoin, carbamazepine) probably have some teratogenic
      potential, but less than valproate; the situation regarding the more recently
      marketed antiepileptic drugs is not yet clear.

PMID- 18324881
TI  - Sudden cardiac death secondary to antidepressant and antipsychotic drugs.
AB  - A number of antipsychotic and antidepressant drugs are known to increase the risk
      of ventricular arrhythmias and sudden cardiac death. Based largely on a concern
      over QT prolongation and the development of life-threatening arrhythmias, a
      number of antipsychotic drugs have been temporarily or permanently withdrawn from
      the market or their use restricted. Some antidepressants and antipsychotics have
      been linked to QT prolongation and the development of Torsade de pointes
      arrhythmias, whereas others have been associated with a Brugada syndrome
      phenotype and the development of polymorphic ventricular arrhythmias. This review
      examines the mechanisms and predisposing factors underlying the development of
      cardiac arrhythmias, and sudden cardiac death, associated with antidepressant and
      antipsychotic drugs in clinical use.

PMID- 18324884
TI  - Human versus HIV: round 2 defeat in AIDS vaccine development.

PMID- 18324885
TI  - CD4+ T-cell subsets: what really counts in preventing HIV disease?

PMID- 18324887
TI  - Targeting mucosal dendritic cells with microbial antigens from probiotic lactic
      acid bacteria.
AB  - The use of vaccines against infectious microbes has been critical to the
      advancement of medicine. Vaccine strategies combined with, or without, adjuvants
      have been established to eradicate various bacterial and viral pathogens. A new
      generation of vaccines is being developed using specific strains of Gram
      positive, lactic acid bacteria and, notably, some probiotic lactobacilli. These
      bacteria have been safely consumed by humans for centuries in fermented foods.
      Thus, they can be orally administered, are well tolerated by recipients and could
      be easily and economically provided to large populations. In this overview, we
      focus on mucosal immunity and how its cellular component(s), particularly
      dendritic cells, can be specifically targeted to deliver immunogenic subunits,
      such as the protective antigen from Bacillus anthracis (the causative agent of
      anthrax). An antigen-specific immune response can be elicited using specific
      strains of Lactobacillus acidophilus expressing the protective antigen. A
      mucosal, dendritic cell-targeted approach increases the bioavailability of an
      immunogen of interest when delivered orally by L. acidophilus. This provides an
      efficiently elegant natural strategy and serves a dual function as an immune
      stimulating adjuvant in vivo.

PMID- 18324888
TI  - Current progress of DNA vaccine studies in humans.
AB  - Despite remarkable progress in the field of DNA vaccine research since its
      discovery in the early 1990 s, the formal acceptance of this novel technology as
      a new modality of human vaccines depends on the successful demonstration of its
      safety and efficacy in advanced clinical trials. Although clinical trials
      conducted so far have provided overwhelming evidence that DNA vaccines are well
      tolerated and have an excellent safety profile, the early designs of DNA vaccines
      failed to demonstrate sufficient immunogenicity in humans. However, studies
      conducted over the last few years have led to promising results, particularly
      when DNA vaccines were used in combination with other forms of vaccines. Here, we
      provide a review of the data from reported DNA vaccine clinical studies with an
      emphasis on the ability of DNA vaccines to elicit antigen-specific, cell-mediated
      and antibody responses in humans. The majority of these trials are designed to
      test candidate vaccines against several major human pathogens and the remaining
      studies tested the immunogenicity of therapeutic vaccines against cancer.

PMID- 18324889
TI  - Therapeutic vaccines against IgE-mediated allergies.
AB  - Therapeutic vaccines targeting various self-molecules is an emerging field of
      vaccine development that is studied extensively in areas such as birth control,
      cancer, allergy and autoimmunity. Promising results have come from a number of
      animal studies and several vaccines are in advanced clinical trials. However, no
      vaccine is currently on the market. This review will focus on the progress in the
      development of vaccines against IgE-mediated allergies. Targets under
      investigation are the IgE molecule itself and several Th2 cytokines, that is, IL
      4, -5, -13, -33, -18 and thymic stromal lymphopoietin. This review will also
      discuss new methods to enhance the immunogenicity of the vaccines and how this
      can contribute to more rapid progress in the field.

PMID- 18324891
TI  - Plasmodium falciparum malaria vaccines in development.
AB  - The development and implementation of a malaria vaccine would constitute a major
      breakthrough for global health. Recently, numerous new candidates have entered
      clinical testing, following strategies that are as diverse as the malaria cycle
      is complex. While promising results have been obtained, some candidate vaccines
      have not fulfilled expectations. The challenges are not merely scientific;
      further progresses will require the development of competent investigator
      networks, partnerships between academics, industry and funding agencies, and
      continuous political commitment. In this review, we present the developmental
      status of all malaria vaccine candidates that are currently in human clinical
      testing against Plasmodium falciparum, as well as selected malaria vaccine
      candidates at preclinical development stage, and discuss the main challenges
      facing the field of malaria vaccine development.

PMID- 18324890
TI  - Current challenges in the development of vaccines for pneumonic plague.
AB  - Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly
      progressing and exceptionally virulent disease. Extensively antibiotic-resistant
      Y. pestis strains exist and we currently lack a safe and effective pneumonic
      plague vaccine. These facts raise concern that Y. pestis may be exploited as a
      bioweapon. Here, I review the history and status of plague vaccine research and
      advocate that pneumonic plague vaccines should strive to prime both humoral and
      cellular immunity.

PMID- 18324892
TI  - Pandemic H5N1 influenza vaccine development: an update.
AB  - The spread and evolution of highly pathogenic influenza A/H5N1 viruses in birds
      worldwide, and the associated human fatalities, have raised concern about an
      imminent influenza pandemic. Studies evaluating the safety and immunogenicity of
      traditional (egg-grown, subvirion and whole virus) vaccines and alternative
      vaccine approaches (recombinant, live-attenuated and adjuvanted vaccines) have
      been performed. Results show that, using unadjuvanted subvirion vaccines, at
      least two vaccine doses containing high dosages of influenza virus hemagglutinin
      are needed to elicit a titer of antibody that has been associated with protection
      in vaccinated subjects. High antigen-dosage requirements may be reduced and
      immunogenicity improved with the use of whole virus vaccines or adjuvants, such
      as MF59 and GlaxoSmithKline proprietary adjuvant. There is a suggestion that
      prepandemic priming against drifted H5N1 variants is possible; however,
      additional data are needed. Newer approaches using live-attenuated, DNA vaccines
      and conserved epitopes are currently under development.

PMID- 18324893
TI  - Influenza and respiratory syncytial virus in the elderly.
AB  - Respiratory infections are one of the leading causes of morbidity and mortality
      worldwide: influenza and respiratory syncytial virus (RSV) are the predominant
      pathogens responsible. Annual vaccination and the use of antiviral drugs provides
      both protection and treatment against influenza, particularly protecting those
      patients most at risk, including the elderly and individuals with chronic
      comorbidities. Currently, there are extremely limited options in the protection
      against RSV infection, making those at-risk patients vulnerable to serious
      disease, complications and death. This review focuses on recent trends in
      respiratory illness in the elderly, particularly focusing on the burden of
      influenza and RSV on hospitalizations and mortality. We discuss the potential
      benefit of influenza vaccination on these outcomes, including the recent
      controversial debate over the effectiveness of influenza vaccination.

PMID- 18324894
TI  - Broadening inclusion of vulnerable populations in HIV vaccine trials.
AB  - The urgent need for a preventive HIV vaccine, as well as the complexities of its
      development, calls for timely and reinforced efforts to ensure vaccine licensure
      for use in a broad range of at-risk populations from the outset. Such an
      integrated strategy to HIV vaccine development should include infants of HIV
      infected women, adolescents and injection drug users. A safe and effective HIV
      vaccine licensed for use in these populations, in addition to sexually active
      adults, would probably have the most timely and profound impact on the HIV/AIDS
      pandemic. Advanced clinical development of HIV vaccines in these vulnerable
      populations imposes particular scientific, operational and ethical challenges.
      Recent developments, including the early termination of a Phase IIb trial,
      present additional previously unanticipated challenges.

PMID- 18324896
TI  - Laparoscopic nephrectomy outside gerota fascia for management of inflammatory
      kidney.
AB  - BACKGROUND AND PURPOSE: A nonfunctioning inflammatory kidney is a challenging
      surgical condition for urologists. Some investigators recommend open surgery
      because of the surgical difficulties caused by the inflammatory process, whereas
      others try to apply the advantages of a "simple" non-hand-assisted laparoscopic
      approach. We report our experience with simple laparoscopic nephrectomy for
      inflammatory kidney management. PATIENTS AND METHODS: From July 2002 through
      December 2006, 50 pure laparoscopic nephrectomies were performed for inflammatory
      kidney (43 because of pyelonephritis, 5 for xanthogranulomatous pyelonephritis
      (XGP), and 2 for pyonephrosis). Histopathologic analysis was the criterion used
      for inflammatory kidney diagnosis. Pain or recurrent urinary tract infection
      associated with a nonfunctioning excluded kidney was the eligibility criterion
      for the procedure. Preoperatively, all patients underwent complete image and
      functional renal assessment. Morcellation was used to remove surgical specimens.
      Conversion index, surgical difficulties, operative time, and postoperative
      complications were evaluated. RESULTS: Conversion was performed in 14 of 50 (28%)
      patients, including two with XGP and one with pyonephrosis. Adhesions, vascular
      (two inferior vena cava) lesions, and intestinal lesions (two colon) were the
      main causes of conversion. Acute pancreatitis developed in one patient, and one
      patient had a wound infection. Reoperations were unnecessary, and no deaths
      occurred. CONCLUSION: Pure laparoscopic nephrectomy was successful in 72% of
      patients with inflammatory kidneys. The laparoscopic dissection was useful even
      in those cases converted to open surgery. This is a high-risk procedure, however,
      and both surgeon and patient must be aware of that before the decision is made
      for this approach.

PMID- 18324897
TI  - Robotic augmentation enterocystoplasty.
AB  - Augmentation enterocystoplasty is an established procedure performed to increase
      bladder capacity and reduce intravesical pressure in patients with neurogenic
      bladder. Although the open surgical procedure remains the most widely accepted
      technique, laparoscopic enterocystoplasty has been described. As an extension of
      the minimally invasive approach, we describe a technique for robotic augmentation
      enterocystoplasty with a completely intracorporeal method. To our knowledge, this
      is the first report of such a technique.

PMID- 18324898
TI  - Ketorolac effectively inhibits ureteral contractility in vitro.
AB  - INTRODUCTION: The use of ketorolac in the management of painful symptoms
      associated with urinary stones is well supported in the literature; however, the
      gastric and renal adverse effects limit the dose and duration of administration.
      As a nonselective cyclooxygenase inhibitor, ketorolac can act locally to help
      control renal colic by inhibiting smooth muscle contractions and inflammation. We
      sought to confirm ketorolac's inhibition of ureteral contractility and determine
      a dose response relationship to identify an effectiveness range. MATERIALS AND
      METHODS: Porcine ureter strips attached to force displacement transducers were
      suspended in organ tissue baths that contained aerated Krebs buffer. Tissues
      equilibrated for 1 hour, and a spontaneous contractility rate was established.
      Tissues were incubated with a concentration-response curve of ketorolac (0.1 nM
      10 microM) for 90 minutes and compared with indomethacin (1 muM) and dimethyl
      sulfoxide (DMSO) 0.1%. Contractility rates were recorded on a polygraph and
      analyzed for changes over exposure time. RESULTS: Ketorolac inhibition of
      ureteral contractility was dose dependent. At 90 minutes, the average percent
      decrease from the spontaneous contraction rate for 0.1 nM ketorolac was 18.2%; 1
      nM, 34.3%; 10 nM, 56.0%; 100 nM, 69.9%; 1 microM, 88.7%; and 10 microM, 98.3%.
      Ureteral contractility was significantly reduced by 1 microM ketorolac (39.0%; P
      = 0.016) at 15 minutes when compared with DMSO. In addition, 1 microM ketorolac
      was not significantly different at any time point from any of the higher doses
      studied. CONCLUSION: Ketorolac inhibition of stretch-induced ureteral
      contractility is concentration-dependent between 1 nM and 1 microM. Local
      administration of ketorolac at these doses may be useful during the management of
      stones while at the same time limiting the risk for adverse effects.

PMID- 18324899
TI  - Laparoscopic nephrectomy with intact specimen extraction for polycystic kidney
      disease.
AB  - PURPOSE: We present our technique and evaluate the experience of laparoscopic
      nephrectomy with intact specimen extraction for patients with autosomal dominant
      polycystic kidney disease (ADPKD). MATERIALS AND METHODS: We retrospectively
      reviewed 16 laparoscopic nephrectomies performed by one laparoscopic surgeon in a
      university hospital between April 2004 and March 2006. Preoperative,
      intraoperative, and postoperative follow-up data are presented. A 3- to 4-port
      transperitoneal laparoscopic approach was used to dissect the involved kidney,
      which was then removed intact through a Pfannenstiel or infraumbilical midline
      incision. RESULTS: A total of 16 patients were included in this study over a 2
      year period. The average patient age was 49 years (range 29-67 years), and the
      average body mass index was 26.9 kg/m(2) (range 19.1-38.3 kg/m(2)). Eleven (69%)
      patients were receiving dialysis. The mean preoperative creatinine level was 520
      mumol/L (range 108-976 mumol/L). Ten right (63%) and six left (37%) nephrectomies
      were performed. No patient had preoperative embolization. The mean operative time
      was 167 minutes (range 95-233 min). The mean blood loss was 76 mL (range 10-200
      mL). No patient received a blood transfusion. The mean kidney pathologic size was
      23 cm (range 16-35 cm), while the mean extraction size was 10.4 cm (range 8-12
      cm). There were no deaths. There was one intraoperative complication (6.25%) and
      three postoperative ones (19%). No procedure was converted to an open approach.
      The mean length of hospital stay was 4 days (range 2-11 d). CONCLUSIONS:
      Laparoscopic nephrectomy for ADPKD is technically feasible and clinically safe.
      In addition to its low morbidity, other advantages of laparoscopic surgery are
      the ability to remove the dissected kidney through a small incision, short
      hospital stay, excellent cosmesis, and fast recovery.

PMID- 18324900
TI  - Critical role of the assistant in laparoscopic and robot-assisted radical
      prostatectomy.
AB  - The literature on standard laparoscopic radical prostatectomy (LRP) and robot
      assisted radical prostatectomy (RARP) is replete with technical descriptions of
      the primary surgeon's responsibility, but deficient with regard to the detailed
      role of the assistant surgeon. This video paper describes the critical role of
      the assistant surgeon and provides tips for the assistant to facilitate these
      operations.

PMID- 18324901
TI  - Single access site laparoscopic radical nephrectomy: initial clinical experience.
AB  - PURPOSE: We present the initial clinical experience with single access site (SAS)
      laparoscopic radical nephrectomy. MATERIALS AND METHODS: An 86-year-old woman
      presented with an 8-cm central-enhancing right renal lesion. The patient elected
      to undergo a laparoscopic radical nephrectomy. A 7-cm paramedian incision was
      made just lateral to the left rectus muscle and cranial to the umbilicus. A
      GelPort was inserted into the incision. Three trocars (12 mm, 10 mm, and 5 mm)
      were placed through the access port, and only standard laparoscopic instruments
      were used. The kidney was mobilized in the standard fashion. Controlling the
      renal artery with nonabsorbable polymer clips and the renal vein with a stapling
      device, the specimen was manipulated into a laparoscopic retrieval bag and
      removed intact. Hemostasis was confirmed, the GelPort was removed, and the 7-cm
      incision was closed. RESULTS: The procedure was completed in 96 minutes without
      complications. Blood loss was estimated to be 10 mL. Postoperatively, the patient
      was treated with intermittent intravenous and oral analgesics. She was discharged
      on postoperative day 2 and tolerated a regular diet. CONCLUSION: This represents
      the initial report of an SAS laparoscopic radical nephrectomy, with intact
      specimen extraction. Using standard laparoscopic instrumentation, the procedure
      was performed safely and effectively, with minimal blood loss, and short
      hospitalization. Additional evaluation and development of this type of approach
      and instrumentation may allow for further expansion of SAS laparoscopic surgery
      in the future.

PMID- 18324902
TI  - Analgesia during extracorporeal shockwave lithotripsy: fentanyl citrate versus
      parecoxib sodium.
AB  - BACKGROUND AND PURPOSE: Shockwave-induced pain may become an important issue
      during extracorporeal shockwave lithotripsy (SWL), although the new generation of
      lithotriptors generally produces less pain than previous models. The aim of the
      study was to compare the analgesic effect of a cyclooxygenase-2-specific
      inhibitor (parecoxib sodium) with that of our standard method of analgesia
      (fentanyl citrate) in patients who needed pain relief when undergoing SWL.
      PATIENTS AND METHODS: Fifty-eight patients who were undergoing SWL for renal
      calculi were randomized to receive intravenously either fentanyl citrate (group
      A, n = 30) or parecoxib sodium (group B, n = 28) when they felt that their pain
      during the session became intolerable. Lithotripsy was recommenced 10 minutes
      after administration of analgesia. The severity of pain before and after
      administration of the analgesic regimens was evaluated using a five-level verbal
      scale. The effectiveness of each drug was evaluated with respect to degree of
      pain relief and ensuing tolerance of the procedure to completion, as well as the
      need for supplementary analgesia (half the standard dose of fentanyl citrate).
      RESULTS: The patients in the two groups were comparable with regard to age, sex,
      body mass index, and stone size. There was no statistically significant
      difference in the maximum energy level achieved as well as in the total number of
      shock waves given in the two groups. Administration of fentanyl citrate resulted
      in alleviation of pain and completion of SWL in 27 patients (90%), whereas
      parecoxib sodium was effective in five patients (17.8%) (P < 0.01). The remaining
      23 patients in group B received supplementary analgesia, and 22 completed the
      lithotripsy session. CONCLUSIONS: Parecoxib sodium was not as effective as
      fentanyl citrate in alleviating pain during SWL. Its use, however, may lower the
      dose of opioid-based analgesia in this group of patients.

PMID- 18324903
TI  - Prospective evaluation of the alterations in the morphology and vascular
      resistance of the renal parenchyma with color Doppler ultrasonography after
      percutaneous nephrolithotomy.
AB  - PURPOSE: To evaluate the kidneys with color Doppler ultrasonography (CDUS) to
      determine whether percutaneous nephrolithotomy (PNL) causes renal parenchymal
      damage. PATIENTS AND METHODS: In 24 patients who underwent unilateral PNL with
      single renal pole access, cortical thickness, echogenicity, and resistive index
      (RI) were measured in each pole of the operated and contralateral kidney
      separately before and at postoperative day (POD) 1, and at 3, 6, and 12 months
      after PNL. RESULTS: The mean age of the patients was 36.67 +/- 14.68 years. The
      serum creatinine level increased significantly immediately after PNL but
      diminished to the preoperative level at POD 1. Changes in serum blood urea
      nitrogen and electrolyte levels were insignificant. Mean cortical thickness
      increased significantly in the access pole and contralateral kidney and
      insignificantly in the nonaffected pole. No statistically significant change was
      recorded in parenchymal echogenicitiy. Statistically significant differences in
      cortical thickness between the access pole and the contralateral kidney and
      between the nonaffected pole and the contralateral kidney disappeared 3 months
      later. Differences in mean cortical thickness between the access pole and the
      nonaffected pole were insignificant at all examination periods. Echogenicity was
      greater in the access pole and the nonaffected pole than in the contralateral
      kidney only at POD 1. No significant difference was noted in the echogenicity
      between the access pole and the nonaffected pole. Mean RIs were lower than the
      universally accepted pathologic RI level (0.70) at all periods. There was no
      statistically significant difference between the mean RI values of the access
      pole, nonaffected pole, and contralateral kidney. CONCLUSION: PNL does not cause
      obvious renal dysfunction and significant parenchymal scarring, which is
      indicated by the decrease in cortical thickness and increases in cortical
      echogenicity and intrarenal RI.

PMID- 18324904
TI  - The double whammy of endogenous insulin antibodies in non-diabetic subjects.
AB  - The presence of high affinity/avidity endogenous insulin antibodies in
      significant amounts in non-diabetic individuals could uniquely be a double
      whammy. Clinically it could trigger pathology, namely hypoglycaemia, and
      analytically it could cause erroneous and potentially misleading results (i.e.,
      falsely high or falsely low) in the key biochemical parameters essential in the
      differential diagnosis of this pathology, namely serum insulin, proinsulin and
      even C-peptide. The purpose of this paper is to highlight the clinical and
      analytical sequelae of endogenous insulin antibodies in (a) delaying or even
      confusing the differential diagnosis of unexpected/unexplained hypoglycaemia, and
      (b) interfering in some immunoassays of pancreatic hormones (commercial or in
      house).

PMID- 18324905
TI  - Rare TA repeats in promoter TATA box of the UDP glucuronosyltranferase (UGT1A1)
      gene in Croatian subjects.
AB  - BACKGROUND: Gilbert's syndrome is a chronic or recurrent mild unconjugated
      hyperbilirubinemia caused by decreased activity of UDP glucuronosyltranferase
      (UGT1A1). The most common cause of Gilbert's syndrome in Caucasians is homozygous
      variant of the A(TA)7TAA promoter polymorphism. Alleles with five or eight TA
      repeats have also been described, but they are very rare in Caucasian
      populations. METHODS: Over a 6-year period (2001-2006), 1109 subjects with
      suspected Gilbert's syndrome were included in this study. Genotyping of (TA)6 and
      (TA)7 alleles was performed using high-resolution electrophoretic separation of
      amplified PCR products on Spreadex EL300 gels. In seven subjects, aberrant
      electrophoretic patterns were observed and additionally sequenced on an ABI Prism
      310 Genetic Analyzer. RESULTS: Genotype distributions for 1102 subjects with
      (TA)6 or (TA)7 alleles were as follows: 54.10%, 26.33% and 18.94% for the
      (TA)7/(TA)7, (TA)6/(TA)7 and (TA)6/(TA)6, respectively. Sequencing of seven
      samples that could not be identified as one of these alleles identified four
      subjects with the (TA)5/(TA)7, two with the (TA)7/(TA)8 and one with the
      (TA)6/(TA)8 genotype. CONCLUSION: Genotyping of TA repeats in the promoter region
      of the UGT1A1 gene revealed the presence of rare alleles with five or eight TA
      repeats, with a very high frequency of the (TA)7 allele in subjects suspected of
      having Gilbert's syndrome.

PMID- 18324906
TI  - Association of high sensitive C-reactive protein with apolipoprotein E
      polymorphism in children and young adults: the Cardiovascular Risk in Young Finns
      Study.
AB  - BACKGROUND: A relation between apolipoprotein E (APOE) genotypes and high
      sensitive C-reactive protein (hsCRP) has been observed in some studies with
      elderly subjects and different patient groups. We studied whether serum hsCRP
      levels are linked with common APOE (epsilon 2, epsilon 3, epsilon 4) polymorphism
      already in children and young adults. METHODS: The study cohort included 1221
      subjects participating in the Cardiovascular Risk in Young Finns Study at age 3
      18 years at baseline in 1980. These subjects were reexamined at the 21-year
      follow-up at age 24-39 years in 2001. APOE phenotypes were examined in 1986,
      serum hsCRP was measured from fresh samples in 2001 and baseline hsCRP (in 1980)
      was measured from frozen samples in 2005. RESULTS: Serum hsCRP was significantly
      associated with APOE phenotypes in children and young adults using multivariate
      analysis adjusted for age, body mass index, smoking, total cholesterol and low
      density lipoprotein cholesterol. Male epsilon 4 carriers had significantly lower
      hsCRP levels both in childhood (p=0.003) and in adulthood (p=0.013). hsCRP
      increased in both phenotype classes (epsilon 4+ and epsilon 4-) during the 21
      year follow-up. Female epsilon 4 carriers had lower hsCRP levels in childhood
      (p=0.032) but not in adulthood (p=0.995). An interaction effect between time and
      APOE phenotype (p=0.045) in relation to hsCRP was observed in females during the
      21-year follow-up. CONCLUSIONS: Common APOE polymorphism affects the level of
      circulating hsCRP already in children and young adults. Male APOE epsilon 4
      carriers have consistently lower hsCRP levels. In females, APOE epsilon 4
      carriers had lower hsCRP levels in childhood but not in adulthood.

PMID- 18324907
TI  - Stability of heparin blood samples during transport based on defined pre
      analytical quality goals.
AB  - BACKGROUND: In many countries and especially in Scandinavia, blood samples drawn
      in primary healthcare are sent to a hospital laboratory for analysis. The samples
      are exposed to various conditions regarding storage time, storage temperature and
      transport form. As these factors can have a severe impact on the quality of
      results, we wanted to study which combination of transport conditions could
      fulfil our pre-defined goals for maximum allowable error. METHODS: Samples from
      406 patients from nine general practitioners (GPs) in two Danish counties were
      sent to two hospitals for analyses, during two periods (winter and summer).
      Transport conditions (mail, courier pick-up, or brought to hospital by public
      coach), storage time, storage temperature and centrifugation requirements were
      different in the two counties. Results were tested for deviation from a "0
      sample", the blood sample taken, centrifuged and separated at the doctor's office
      within 45-60 min. This sample was considered as the best estimate of a comparison
      value. RESULTS: The pre-set quality goals were fulfilled for all the investigated
      components for samples transported to hospital by courier either as whole blood
      or as "on gel" after centrifugation, as long as the samples were stored at 20-25
      degrees C and centrifuged/analysed within 5-6 h. A total of 4% of the samples
      sent by mail had mismatched identity, probably due to plasma being transferred to
      a new tube. CONCLUSIONS: Samples can be sent as unprocessed anticoagulated whole
      blood if the above mentioned conditions are met. There is no need for
      centrifugation in the primary sector. Neither mailing of samples with plasma "on
      gel" nor public transport by coach bus fulfil our analytical goals.

PMID- 18324908
TI  - Strenuous exercise activates growth factors and chemokines over-expression in
      human serum of top-level triathlon athletes during a competitive season.
AB  - Regular exercise offers protection against all-cause mortality, primarily by
      protection against atherosclerosis and insulin resistance. There is evidence that
      physical training is effective as a treatment in patients with chronic heart
      diseases and type 2 diabetes. With excessive repetition of the training stimulus,
      local inflammation can generate a systemic inflammatory response. Cytokines play
      an important role in these processes. Our data confirm that cytokines that are
      considered to induce systemic bioactivity following exercise are not alone, but
      also growth factors and chemokines, which are secreted in exercise without the
      involvement of traditional proinflammatory cytokines, could be potent angiogenic
      factors.

PMID- 18324909
TI  - Usefulness of six non-proprietary indirect markers of liver fibrosis in patients
      with chronic hepatitis C.
AB  - BACKGROUND: The aim of the study was to perform a comprehensive diagnostic
      evaluation of six popular, non-proprietary, indirect markers of liver fibrosis in
      a cohort of patients with chronic hepatitis C representing the full spectrum of
      disease severity. METHODS: A total of 167 consecutive, hepatitis C virus RNA
      positive, untreated patients with chronic hepatitis C were studied. Liver biopsy
      with histological evaluation and age/platelet index, aspartate
      aminotransferase/alanine aminotransferase ratio, aspartate aminotransferase to
      platelet ratio index, Bonacini's discriminant score, Forn's fibrosis index and
      FibroIndex were assessed in all patients. RESULTS: The area under the receiver
      operating characteristic curves of the six tests was always greater when
      performed to discriminate patients with METAVIR score F4 than when assessed to
      discriminate patients with METAVIR score > or =F2. At step-wise discriminant
      analysis the only indirect marker of fibrosis entered was FibroIndex, with the
      following correct classification of the patients: total=52.1, patients with
      scores F0-F1=62.2, patients with scores F2-F3=26.0 and patients with score
      F4=68.4. CONCLUSIONS: The ability to correctly classify patients using a panel of
      non-proprietary indirect markers of liver fibrosis is far from being ideal. Among
      them, FibroIndex appears to possess the best discriminating capacity. The
      simultaneous use of several indirect markers of liver fibrosis does not improve
      their diagnostic accuracy.

PMID- 18324910
TI  - Different biological matrices (serum and plasma) utilization in consolidation
      processes: evaluation of seven Access immunoassays.
AB  - BACKGROUND: The compatibility of immunoassay tests in different sample matrices
      is extremely important during the assay validation process. In this study, we
      investigated the interchangeability of some Access (and therefore all the UniCel
      Family platforms) assays between serum and plasma. METHODS: We tested
      approximately 200 samples in parallel between serum and lithium heparin plasma
      for seven analytes: alpha-fetoprotein (AFP), carcino-embryonic antigen (CEA),
      total prostate specific antigen (tPSA), free prostate specific antigen (fPSA),
      digoxin, progesterone and unconjugated estriol (uE3). We used the Access2
      Immunoassay System (Beckman Coulter), a fully automated random access system with
      a chemiluminescent signal. We performed statistical comparative analysis using
      two commercially available programs, Analyze-it from Microsoft Excel and MedCalc
      Software, and a dedicated statistical program. RESULTS: Firstly, we showed the
      results of the statistical tests performed on each population to verify their
      distribution. Analysis by several statistical tests (Passing and Bablok
      regression, Youden and Bland and Altman diagrams, the Mountain plot and
      multivariate analysis) showed that all the assays studied were valid in both
      serum and lithium heparin plasma matrices. CONCLUSIONS: As all Access and UniCel
      Family instruments use the same reagent packs, these results are transferable to
      all Beckman Coulter immunochemistry platforms, without a commutability problem
      between serum and plasma and without a need for establishment of a plasma
      reference interval.

PMID- 18324911
TI  - Homocysteine measurement by Vitros Microtip homocysteine assay.
AB  - BACKGROUND: Elevated circulating total homocysteine is an independent vascular
      risk factor. Enzymatic homocysteine measurements represent an alternative to HPLC
      or immunochemistry-based assays, suitable for automation. Here, we report on
      analytical performance of a commercial cystathionine beta-synthase-based assay,
      for use on Vitros automated analyzers. METHODS: Linear range, limit of detection
      and analytical sensitivity were inferred from duplicate measurements of
      homocystine standard solutions (1-65 micromol/L). Imprecision was assessed using
      commercial controls according to NCCLS EP5-A2 and accuracy using NIST-SRM1955
      reference material. Agreement with a clinically validated HPLC method was
      examined on 207 patient samples. RESULTS: The enzymatic assay was linear from 1
      to 90 micromol/L homocysteine. Total (within-day) imprecision ranged from 4.5
      (3.9)% to 2.8 (1.6)% at homocysteine 9.7-43.2 micromol/L. Accuracy was acceptable
      at 8.9 and 17.7 micromol/L homocysteine, with +6.4% and -1.2% bias, respectively,
      but showed substantial negative bias (-20.1%) at 4.0 micromol/L. High
      triglycerides (19.8 micromol/L) negatively interfered. The enzymatic method was
      slightly less sensitive than the HPLC method (limit of detection 0.7 and 0.2
      micromol/L, respectively) but correlated well with the latter (r2=0.9997,
      slope=1.04, intercept=-0.66 micromol/L) and was more precise (p<0.05).
      CONCLUSIONS: The Vitros homocysteine assay met the CLIA Desirable Analytical
      Quality Specifications at homocysteine > or = 9 micromol/L. Its analytical
      performance and suitability for automation make the Vitros assay an analytically
      acceptable alternative to HPLC-based methods.

PMID- 18324912
TI  - Genetic delivery of the murine equivalent of bevacizumab (avastin), an anti
      vascular endothelial growth factor monoclonal antibody, to suppress growth of
      human tumors in immunodeficient mice.
AB  - Vascular endothelial growth factor (VEGF) produced by tumor cells plays a central
      role in stimulating angiogenesis required for solid tumor growth. VEGF-specific
      antibodies inhibit tumor cell line growth in animal models and a humanized
      monoclonal anti-VEGF antibody (bevacizumab [Avastin]) is approved as a treatment
      for metastatic cancer. We hypothesized that administration of an adenoviral (Ad)
      vector expressing the murine monoclonal antibody equivalent of bevacizumab would
      suppress human tumor growth in vivo. The Ad vector (AdalphaVEGF) encodes the
      light chain and heavy chain cDNAs of monoclonal antibody A.4.6.1, a murine
      antibody that specifically recognizes human VEGF with the same antigen-binding
      site as bevacizumab. AdalphaVEGF efficacy in vivo was evaluated with A-673
      rhabdomyosarcoma and DU 145 prostate carcinoma cells in human tumor cell
      xenografts in SCID mice. For both tumor models, AdalphaVEGF directed the
      expression of high anti-human VEGF IgG antibody titers in vivo, the numbers of
      mitotic nuclei and blood vessels in the tumor were significantly decreased (p <
      0.05), tumor growth was suppressed (p < 0.05), and there was increased survival
      (p < 0.005). Thus, AdalphaVEGF, encoding a murine monoclonal antibody that is the
      equivalent of bevacizumab, effectively suppresses the growth of human tumors,
      suggesting gene therapy as an alternative to bevacizumab monoclonal antibody
      therapy.

PMID- 18324913
TI  - Proposed categorization of pathological states of EBV-associated T/natural killer
      cell lymphoproliferative disorder (LPD) in children and young adults: overlap
      with chronic active EBV infection and infantile fulminant EBV T-LPD.
AB  - EBV-associated T/natural killer (NK)-cell lymphoproliferative disorder (EBV-T/NK
      LPD) of children and young adults is generally referred to with the blanket
      nosological term of severe chronic active EBV infection (CAEBV). This disease is
      rare, associated with high morbidity and mortality, and appears to be more
      prevalent in East Asian countries. But because there is no grading or
      categorization system for CAEBV, pathologists and clinicians often disagree
      regarding diagnosis and therapy. EBV-T/NK LPD includes polyclonal, oligoclonal,
      and monoclonal proliferation of cytotoxic T and/or NK cells. Moreover, a unique
      disease previously described as infantile fulminant EBV-associated T-LPD has been
      identified and overlaps with EBV-T/NK LPD. In the present review a
      clinicopathological categorization of EBV-T/NK LPD is proposed, based on
      pathological evaluation and molecular data, as follows: (i) category A1,
      polymorphic LPD without clonal proliferation of EBV-infected cells; (ii) category
      A2, polymorphic LPD with clonality; (iii) category A3, monomorphic LPD (T-cell or
      NK cell lymphoma/leukemia) with clonality; and (iv) category B, monomorphic LPD
      (T-cell lymphoma) with clonality and fulminant course. Categories A1, A2, and A3
      possibly constitute a continuous spectrum and together are equivalent to CAEBV.
      Category B is the exact equivalent of infantile fulminant EBV-associated T-LPD.
      It is expected that this categorization system will provide a guide for the
      better understanding of this disorder. This proposal was approved at the third
      meeting of the Asian Hematopathology Association (Nagoya, 2006).

PMID- 18324914
TI  - Genotyping of the cagA gene of Helicobacter pylori on immunohistochemistry with
      East Asian CagA-specific antibody.
AB  - The cytotoxin-associated antigen A (CagA) of Helicobacter pylori prevalent in
      East Asian countries, where the mortality rate due to gastric cancer is high, has
      been reported to be structurally different from that in Western countries, where
      the gastric cancer mortality rate is relatively low. Based on the structural
      features of the EPIYA motifs located at the carboxyl terminal of the protein,
      CagA was subdivided into two types: East Asian CagA and Western CagA. A recent
      study suggested that immunohistochemistry with anti-East Asian-specific antibody
      (alpha-EAS Ab), which was specifically immunoreactive with East Asian CagA but
      not with Western CagA, may be useful for diagnosis of the cagA genotype. To
      further evaluate the value of this diagnostic method in terms of sensitivity,
      specificity, and accuracy, 143 gastric biopsy specimens with alpha-EAS Ab were
      analyzed on immunohistochemistry and compared with the sequencing of the cagA
      gene. It was found that diagnosis of the cagA genotype of H. pylori on
      immunohistochemistry using the alpha-EAS Ab was highly sensitive (sensitivity
      93.2%) and specific (specificity 72.7%), suggesting that immunohistochemical
      diagnosis of the cagA genotype is useful for diagnosis of the cagA genotype.

PMID- 18324915
TI  - RHEB expression in fibroadenomas of the breast.
AB  - Although fibroadenoma is one of the most common types of benign breast tumor,
      genes specific to the tumor have not been identified. Microarrays were used to
      identify differentially expressed genes between fibroadenoma and infiltrating
      ductal carcinoma. The comparative expression of one of the identified genes, RAS
      homolog enriched in the brain (RHEB), was further explored using reverse
      transcriptase-polymerase chain reaction (RT-PCR). Microarray analysis was
      performed on tissue samples from five patients with fibroadenoma. In the
      fibroadenoma samples, the genes HDAC1, ROS1, TNFRSF10A, WASP2, TYRP1, WEE1, and
      RHEB were expressed at levels more than twofold higher than in the normal
      tissues. RT-PCR for RHEB indicated increased expression of RHEB in fibroadenoma
      compared to breast cancer. When studied with real-time PCR, the average RHEB/beta
      actin ratio in fibroadenoma samples was 1.99, 2.46-fold greater than the average
      RHEB/beta-actin ratio in breast carcinoma of 0.81 (P < 0.01).
      Immunohistochemistry and PCR followed by microdissection shows increased
      expression of RHEB in epithelial cells compared to the stromal cells of
      fibroadenoma. Therefore, RHEB could be used cytopathologically to distinguish
      fibroadenoma from malignant breast carcinomas as a secondary diagnostic tool.

PMID- 18324916
TI  - Significance of GLUT1 expression in adenocarcinoma and adenoma of the ampulla of
      Vater.
AB  - The expression of glucose transporter protein 1 (GLUT1) in malignant tumors is
      increased due to the higher metabolic needs of the proliferating cell
      populations. Aberrant GLUT1 expression is exhibited in a wide spectrum of
      epithelial malignancies and their precursors, which occur with low frequency and
      intensity; aberrant GLUT1 expression does not occur in normal epithelial cells.
      The expression of GLUT1 in tumors of the ampulla of Vater was evaluated on
      immunohistochemistry, and the relationships of GLUT1 expression to histological
      parameters and p53 expression were analyzed. Twenty-one (58.3%) of 36
      adenocarcinomas and three (17.6%) of 17 adenomas had GLUT1 immunoreactivity. None
      of the regenerating or normal epithelia had any immunoreactivity. No significant
      relationships were found between GLUT1 expression and histological parameters or
      p53 expression. It was found that histological subtypes originated from different
      epithelium were strongly related to different macroscopic types. In the ampulla
      of Vater, GLUT1 expression was associated with malignant change, and might be a
      useful marker of malignancy.

PMID- 18324917
TI  - Localized malignant mesenteric mesothelioma causing small bowel obstruction.
AB  - Malignant mesothelioma is an uncommon lethal neoplasm in the serous membrane in
      which peritoneal mesothelioma is a rarer form. Herein is reported a case of
      malignant mesothelioma presenting as a localized mass inside the mesentery
      causing focal luminal obstruction of the small intestine. The diagnosis of
      malignant mesothelioma was obtained on repeat double balloon endoscopic biopsy.
      Partial resection of the small intestine along with the mesentery was performed,
      followed by a course of chemotherapy. No relapse of the disease has been found in
      the 8 months' follow up radiologically. To the best of the authors' knowledge
      this is the first reported case of localized malignant mesothelioma arising
      inside the mesentery. Mesothelioma should be considered as the differential
      diagnosis when small bowel obstruction occurs with unknown primary neoplasm.

PMID- 18324918
TI  - Ovarian undifferentiated carcinoma resembling giant cell carcinoma of the lung.
AB  - Giant cell carcinoma (GCC) is a highly aggressive variant of sarcomatoid
      carcinoma of the lung. To date, however, there have been no reported cases of
      ovarian carcinoma mainly composed of GCC. Herein is reported the case of a 54
      year-old Japanese woman with an undifferentiated ovarian carcinoma producing
      granulocyte colony-stimulating factor (G-CSF) and an inflammatory cytokine.
      Histologically, the tumor was composed of cohesive nests or discohesive
      pleomorphic mononucleated or multinucleated tumor giant cells, accompanied by
      inflammatory cell infiltration and emperipolesis. Immunohistochemically, the
      tumor cells were focally positive for epithelial membrane antigen and cytokeratin
      7. Clinically, after the initial surgery, the tumor had rapid regrowth along with
      the production of G-CSF and an inflammatory cytokine. Adjuvant chemotherapy was
      administered but induced severe heart failure and severe neutropenia, probably
      due to the presence of hypercytokinemia and excess G-CSF. Upon the appearance of
      these fatal side-effects the chemotherapy was immediately discontinued and
      replaced with radiotherapy. The recognition of this type of ovarian tumor is
      important for clinical management, because adjuvant chemotherapy is the standard
      treatment for clinical management of epithelial ovarian cancer.

PMID- 18324919
TI  - Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma presenting as
      a bladder neoplasm.
AB  - Malignant lymphoma presenting in the bladder has been classified in primary
      cases, as the first sign of disseminated disease and as a secondary infiltration.
      Most of the examples in the literature have been reported as single cases.
      Reported herein is the case of a 45-year-old man with an anaplastic large cell
      lymphoma (anaplastic lymphoma kinase (ALK) and granzyme B positive) that
      presented as a bladder neoplasm. The morphological differential diagnosis was
      complex because the EMA-positive immunophenotype, CD45 and CD3 negativity and the
      clinical manifestation simulated a transitional cell carcinoma. It is important
      to be aware of its existence because a poorly differentiated bladder carcinoma
      cannot be ruled out if CD30 and ALK immunostaining are not performed. T-cell
      receptor-gamma clonal rearrangement could be also helpful in these cases.
      Although bladder involvement by recurrent lymphoma is a sign of widely
      disseminated disease and it is associated with a very poor prognosis, it seems
      that chemotherapeutic regimens in this kind of ALK-positive lymphoma could be
      effective, given that the present patient had an impressive response to
      chemotherapy treatment.

PMID- 18324920
TI  - Pleural MALT lymphoma diagnosed on thoracoscopic resection under local anesthesia
      using an insulation-tipped diathermic knife.
AB  - A 79-year-old man presented with back pain. Chest CT scan showed elevated nodular
      lesions in the right parietal pleurae with pleural effusion. There were no
      intrapulmonary or mediastinal abnormalities. Under local anesthesia, right
      thoracoscopy and subsequent thoracoscopic pleural resection were performed using
      an insulation-tipped diathermic knife (IT-knife). The resected pleura, 2.2 cm in
      diameter, had a rough granular surface. Lymphoid cells histologically infiltrated
      diffusely into the pleura. They were composed of centrocyte-like and monocytoid
      cells. On immunohistochemistry they were found to be positive for Bcl2, CD20,
      CD45RB and CD79a, but negative for CD3, CD5, CD10 and cyclin D1. EBV-encoded
      small RNA-1 (EBER-1) in situ hybridization was negative. A diagnosis of
      extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
      (MALT lymphoma) arising in the pleura was therefore made. To the authors'
      knowledge this is the first case in which IT-knife was used for diagnosis of a
      pleural lesion. This large, single-piece, only slightly crushed pleural specimen,
      enabled study of histopathological findings (listed here) that could not have
      been obtained on conventional biopsy: (i) lack of apparent evidence of
      plasmacytic differentiation; (ii) no recognition of lymphoid follicles; (iii)
      mesothelial cells not infiltrated by lymphoma cell clusters; (iv) thin layer of
      hyperplastic mesothelial cells continuously covering the surface; and (v) no
      proliferation of fibroblast-like submesothelial cells.

PMID- 18324921
TI  - Genetically modified parasites and the immune response.

PMID- 18324922
TI  - Expression of helminth genes in Leishmania: an experimental transfection system
      to test immunological function.
AB  - Functional analysis of genes from parasitic helminths requires, at the present
      time, heterologous expression. We have adapted the well-characterized system of
      transfection in Leishmania protozoal parasites, as a means of analysing the
      effect of single filarial genes on the mammalian immune system. For example,
      testing the function of the Brugia malayi abundant larval transcript (ALT) gene
      transfected Leishmania mexicana were found to be significantly more virulent in
      macrophages in vitro. The course of infection in vivo is also aggravated by
      expression of the ALT gene. Examples are also given of transgenes which reduced
      in vitro growth within macrophages, as well as others which exert no effect on
      the protozoal parasitism. Thus, Leishmania transfection provides a tractable
      system to analyse helminth gene function within the context of the host immune
      system.

PMID- 18324923
TI  - Transgenesis and neuronal ablation in parasitic nematodes: revolutionary new
      tools to dissect host-parasite interactions.
AB  - Ease of experimental gene transfer into viral and prokaryotic pathogens has made
      transgenesis a powerful tool for investigating the interactions of these
      pathogens with the host immune system. Recent advances have made this approach
      feasible for more complex protozoan parasites. By contrast, the lack of a system
      for heritable transgenesis in parasitic nematodes has hampered progress toward
      understanding the development of nematode-specific cellular responses. Recently,
      however, significant strides towards such a system have been made in several
      parasitic nematodes, and the possible applications of these in immunological
      research should now be contemplated. In addition, methods for targeted cell
      ablation have been successfully adapted from Caenorhabditis elegans methodology
      and applied to studies of neurobiology and behaviour in Strongyloides
      stercoralis. Together, these new technical developments offer exciting new tools
      to interrogate multiple aspects of the host-parasite interaction following
      nematode infection.

PMID- 18324924
TI  - Reverse genetics and the study of the immune response to schistosomes.
AB  - The sequencing of the schistosome genome and the establishment of techniques for
      RNAi and transient transfection in these parasites have opened the door for a
      reverse genetics approach to studying schistosomes. One of the most intriguing
      aspects of schistosome biology is the interaction of these parasites with the
      immune system. The immune response underlies the ability of the host to survive
      while infected and to eventually develop resistance to further infection.
      However, it is also instrumental in the development of disease due to its role
      orchestrating granuloma formation around tissue-trapped parasite eggs. While
      schistosomes have clearly evolved mechanisms for evading host immune responses,
      their normal development is, paradoxically, also dependent upon the presence of a
      normal immune system. This article will review recent advances in the development
      of tools for studying gene function in schistosomes, and discuss how these new
      tools may be exploited to investigate issues of key importance in the interaction
      of schistosomes with the host immune system.

PMID- 18324925
TI  - What can transgenic parasites tell us about the development of Plasmodium
      specific immune responses?
AB  - Malaria infects 500 million people and kills an estimated 2.7 million annually,
      representing one of the most significant diseases in the world. However, efforts
      to develop effective vaccines have met with limited success. One reason is our
      lack of basic knowledge of how and where the immune system responds to parasite
      antigens. This is important as the early events during induction of an immune
      response influence the acquisition of effector function and development of memory
      responses. Our knowledge of the interactions of Plasmodia with the host immune
      system has largely been derived through in vitro study. This is a significant
      issue as the component parts of the immune system do not work in isolation and
      their interactions occur in distinct and specialized micro- and macro-anatomical
      locations that can only be assessed in the physiological context, in vivo. In
      this context, the availability of transgenic malaria parasites over the last 10
      years has greatly enhanced our ability to understand and evaluate factors
      involved in host-parasite interactions in vivo. In this article, we review the
      current status of this area and speculate on what parasite transgenesis
      approaches will tell us about the development of Plasmodium-specific immune
      responses in the future.

PMID- 18324926
TI  - Synthesis of water soluble bis-triazenoquinazolines: an unusual predicted mode of
      binding to the epidermal growth factor receptor tyrosine kinase.
AB  - A novel type of 3,3-disubstituted bis-triazenes containing an ethylaminoethyl
      linker flanked by two identical anilinoquinazoline ring was synthesized. These
      model molecules contained an N-ethylaminomorpholine moiety designed to enhance
      water solubility. Despite their significant bulkiness, they blocked epidermal
      growth factor receptor (EGFR) tyrosine kinase in a dose-dependent manner with
      IC(50) values in low micromolar range. Molecular modeling to predict the
      interactions of the molecule with the ATP binding site of EGFR suggests that the
      N-ethylaminomorpholine side chain plays a binding role.

PMID- 18324928
TI  - Combination therapy in the management of mixed dyslipidaemia.
AB  - Whilst statin monotherapy is often sufficient to reach LDL-C goals, treatment may
      not reach all lipid goals in individuals with mixed dyslipidaemia typically
      associated with metabolic syndrome or type 2 diabetes. Double or triple
      combination therapy, which provides the opportunity to address multiple lipid
      abnormalities simultaneously, may be required to achieve targets in some
      patients. Addition of fenofibrate or niacin (nicotinic acid) to statin therapy is
      likely to be the first option, as recommended by national treatment guidelines;
      omega-3 fatty acids may also be useful. Careful monitoring is required when
      adding additional agents given the increased potential for drug interactions and
      side effects.

PMID- 18324930
TI  - Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A-V
      deficiency due to a novel mutation in the APOA5 gene.
AB  - APOA5 encodes a novel apolipoprotein (apo A-V) which appears to be a modulator of
      plasma triglyceride (TG). In apoA5 knock out mice plasma TG level increases
      almost fourfold, whereas in human APOA5 transgenic mice it decreases by 70%. Some
      SNPs in the APOA5 gene have been associated with variations in plasma TG in
      humans. In addition, hypertriglyceridaemic (HTG) patients have been identified
      who carried rare nonsense mutations in the APOA5 gene (Q139X and Q148X),
      predicted to result in apo A-V deficiency. In this study we report a 17-year-old
      male with high TG and low high density lipoprotein cholesterol (HDL-C), who at
      the age of two had been found to have severe HTG and eruptive xanthomas
      suggesting a chylomicronaemia syndrome. Plasma postheparin LPL activity, however,
      was normal and no mutations were found in LPL and APOC2 genes. The sequence of
      APOA5 gene revealed that the patient was homozygous for a point mutation (c.289
      C>T) in exon 4, converting glutamine codon at position 97 into a termination
      codon (Q97X). Apo A-V was not detected in patient's plasma, indicating that he
      had complete apo A-V deficiency. The administration of a low-fat and low
      oligosaccharide diet, either alone or supplemented with omega-3 fatty acids,
      started early in life, reduced plasma TG to a great extent but had a negligible
      effect on plasma HDL-C. Loss of function mutations of APOA5 gene may be the cause
      of severe HTG in patients without mutations in LPL and APOC2 genes.

PMID- 18324929
TI  - High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2
      predict improvement in insulin sensitivity following pioglitazone treatment of
      drug-naive type 2 diabetic subjects.
AB  - CONTEXT: High levels of circulating retinol-binding protein 4 (RBP4) and baseline
      expression of adipogenic genes correlate with subsequent improvement in insulin
      sensitivity following Thiazolidinedione (TZD) treatment. OBJECTIVE: The aim was
      to identify baseline characteristics and early changes related to TZD treatment
      that could predict a good treatment response. DESIGN: Subjects were examined with
      oral glucose tolerance test, intravenous glucose tolerance test,
      hyperinsulinaemic euglycaemic clamp, body composition and standard blood sampling
      at baseline and after 4 and 12 weeks treatment. Subcutaneous adipose tissue
      biopsies were taken from the abdominal region at baseline, after 3 days and 4
      weeks treatment to examine the gene expression profile. SETTING: Research
      laboratory in a University hospital. PARTICIPANTS: Ten newly diagnosed and
      previously untreated type 2 diabetic subjects were treated with pioglitazone for
      3 months. MAIN OUTCOME MEASURES: Baseline characteristics and early changes
      related to TZD treatment that could predict the response after 3 months. RESULTS:
      Pioglitazone improved insulin sensitivity after 4 weeks combined with lower
      glucose and insulin levels without any change in BMI. It was accompanied by lower
      circulating resistin and plasminogen activator inhibitor-1 levels rapidly
      increased levels of circulating total and high molecular weight adiponectin as
      well as adiponectin and adipocyte fatty acid-binding protein (aP2) mRNA
      expression in the adipose tissue. High levels of circulating RBP4 at baseline and
      adipose tissue expression of aP2, proliferator-activated receptor-gamma
      coactivator 1 alpha (PGC-1alpha) and uncoupling protein 2 (UCP-2) predicted a
      good treatment response measured as improvement in insulin-stimulated whole-body
      glucose uptake after 3 months. CONCLUSIONS: Circulating levels of RBP4 as an
      index of insulin sensitivity and mRNA levels of adipogenic genes correlate with
      the subsequent improvement in insulin sensitivity following TZD treatment.

PMID- 18324932
TI  - Criteria for evaluation of measurement properties of clinical balance measures
      for use in fall prevention studies.
AB  - Work Package 3 of the Prevention of Falls Network Europe has evaluated
      measurement properties of clinical balance measures to be used to: (1) select
      participants for interventions with the goal to prevent falls in older people,
      and (2) assess the results of such intervention on balance function. Inclusion in
      a fall prevention study may be based on measures identifying subjects who have
      impaired balance or increased risk of future falls. We propose that an
      appropriate statistical method to analyse discriminative ability of a balance
      measure is discriminant analysis or logistic regression analysis. The optimal cut
      off score is best determined by plotting a receiver-operating-characteristic
      curve for different cut-off values. The evaluation of predictors for risk of
      future falls should be based on a study design with a prospective data collection
      of falls. Sensitivity to change is a measurement property needed to evaluate the
      outcome of an intervention. The standardized response mean is frequently
      encountered in the literature and is recommended as a statistical measure of
      sensitivity to change in the context of an intervention study. Adequate
      reliability is a prerequisite for consistent measurement. Relative reliability
      may be reported as an intraclass correlation coefficient and absolute reliability
      as the within-subject standard deviation (s(w)), also called standard error of
      measurement. When measurement error is proportional to the score, calculation of
      a coefficient of variation can be considered. In a second paper, the authors will
      evaluate clinical balance measures for use in fall prevention studies based upon
      criteria recommended in this report.

PMID- 18324933
TI  - Factors associated with physical activity of patients with osteoarthritis of the
      lower limb.
AB  - OBJECTIVE: In patients with osteoarthritis (OA), moderate physical activity (PA)
      can reduce the progress of joint damage. PA is therefore an important target of
      in the non-surgical treatment of OA. To know about factors associated with PA can
      increase the success of interventions aiming at increasing PA. The aim of the
      study was to determine predictors of PA in patients suffering from OA to the hip
      or to the knee. METHODS: In total, 1250 outpatients from 75 general practices
      were consecutively approached, 1021 returned questionnaires containing
      sociodemographic data, and short forms of the International Physical Activity
      Questionnaire (IPAQ), the Arthritis Impact Measurement Scale and the Patient
      Health Questionnaire to assess concomitant depression. A hierarchical stepwise
      multiple linear regression analysis with the IPAQ continuous score as dependent
      variable was performed. RESULTS: Comparison of our findings with General
      population suggests that the overall PA of OA patients is decreased. Main
      predictors of PA were physical limitation to the lower body (beta = -0.179; P =
      0.001), social contacts (P = -0.134; P < 0.001), pain (beta =-0.120; P = 0.001),
      age (beta = -0.110; P = 0.004) and the body mass index (beta =-0.043; P < 0.001).
      CONCLUSION: The findings emphasize the influence of physical as well as
      psychosocial factors on PA of patients with OA and should help to tailor future
      interventions more appropriately. Further research is needed to determine if
      these tailored interventions will result in better compliance and in increased
      PA.

PMID- 18324934
TI  - Impact of an educational intervention on internal medicine residents' physical
      activity counselling: the Pressure System Model.
AB  - RATIONALE, AIMS AND OBJECTIVES: Systematic reviews point to inconclusive evidence
      that counselling patients in a primary care setting is effective in increasing
      adults' physical activity (PA) levels. This study evaluates the impact of an
      innovative physician counselling programme on physicians' PA counselling
      behaviour and their patients' PA levels. METHODS: A controlled educational study
      conducted at six Yale School of Medicine hospitals. Sixty-five internal medicine
      residents and 316 primary care patients were randomized to intervention or
      control groups. Intervention physicians participated in five interactive sessions
      outlining details of the Pressure System Model, while control physicians received
      usual residency training. Intervention and control patients' PA levels and
      residents counselling behaviour were assessed using a validated questionnaire and
      compared pre- and post intervention. Data analysis was performed using paired t
      tests and repeated measures anova. RESULTS: At 6-month follow-up intervention,
      patients' PA levels increased significantly from baseline (1.77 +/- 0.84; P =
      0.0376). A similar pattern was observed after 12 months (1.94 +/- 0.98; P =
      0.0486). Control patients' PA did not change significantly from baseline at 6 or
      12 months (0.35 +/- 1.00; P = 0.7224 and 0.99 +/- 1.52; P = 0.5160,
      respectively). At 12 months, intervention residents provided PA counselling 1.5
      times more than they did at baseline (P < 0.05) compared with no significant
      changes in the control group. CONCLUSIONS: The present study has shown that
      providing residents with a practical tool, enabling them to deal with patients'
      barriers and previous failure in behavioural change, is efficacious in increasing
      PA levels of adult patients.

PMID- 18324935
TI  - Do gynaecology outpatients use the Internet to seek health information? A
      questionnaire survey.
AB  - BACKGROUND: The Internet is a rich source of medical information and the general
      opinion among doctors is that the number of patients attending clinics with
      information from a web search is increasing. The purpose of this study was to
      assess the demographics of those who access the Internet and their attitudes
      towards the quality and usefulness of information provided by the Internet. This
      study also looked at the various sources of health information and the
      satisfaction rates. DESIGN: Cross-sectional observational study. The study group
      consisted of a cohort of women attending the gynaecology outpatient clinic at a
      district general hospital in the United Kingdom. In total, 484 patients attending
      the gynaecology outpatient clinic completed a questionnaire which included 13
      structured questions regarding access to and attitudes towards the Internet and
      other health sources of information. SETTING: Questionnaires were distributed to
      564 women attending gynaecology outpatient clinics for 3 months from 1 June 2005.
      RESULTS: A total of 484 patients (85.6%) completed the questionnaire. Age range
      was 41-65 years and the median education level was completion of General
      Certificate of Secondary Education (GCSE). In total, 360/484 (74%) had sought
      health information about their condition from a variety of sources before
      attending the outpatient clinic. In total, 399/484 (82.4%) respondents had access
      to the Internet. Of 399 with access, 107 (26.8%) of the patients used the
      Internet to find information about their condition before their appointment.
      General practitioners remain as the primary source of health information, mainly
      to improve the knowledge of the condition. A total of 78/107 (73.3%) who had used
      the Internet before their appointment would like to continue using the Internet
      as a health information resource. CONCLUSION: A significant proportion of
      patients had access to the Internet to find health information. The widespread
      availability and increased usage of medical websites by patients raises important
      issues regarding the need for quality control and impacts on the doctor-patient
      relationship.

PMID- 18324936
TI  - Projection of the supply of and demand for board-certified nephrologists for ESRD
      in Taiwan.
AB  - OBJECTIVE: Taiwan is the country where end-stage renal disease (ESRD) is most
      prevalent. The purpose of this study was to investigate whether the rising demand
      for dialysis or transplantation as a result of ESRD can be balanced by the supply
      of board-certified (B-C) nephrologists. METHODS: Two Markov processes were
      applied for the projection of the supply of B-C nephrologists in ESRD and for the
      projection of the demand from ESRD in 2020, assuming linear, exponential growth
      and no increase. RESULTS: The supply of B-C nephrologists was projected at 1346
      in 2020. To make allowance for the share of total time of professional activities
      in full-time equivalent (FTE) for B-C nephrologists, the demand was 1556, 962 and
      2652 with assumptions of steady, linear and exponential growth, respectively. By
      the year 2020, 210 and 1306 additional FTE nephrologists will be required to
      meet, respectively, a linear and an exponential increase in demand from ESRD.
      CONCLUSIONS: The projection of the supply of and the demand for B-C nephrologists
      was made in this study using two Markov processes. The methods and results can be
      adopted as a reference for health manpower planning on B-C nephrologists.

PMID- 18324937
TI  - Computing hospitalization rates in presence of repeated events: impact and
      countermeasures to avoid misinterpretation.
AB  - RATIONALE, AIMS AND OBJECTIVES: The admission rate, including both first and
      recurrent events, is a clear overall measure of hospital utilization, its
      variability accounting for individual propensity to disease recurrence. METHOD:
      In this paper, we compared two variance estimators derived from the Poisson and
      negative binomial distribution of directly and indirectly age/gender-standardized
      hospitalization rates allowing for multiple events. The latter approach
      accommodates departures from the assumption of randomness of repeated events
      required by the Poisson distribution. We apply these methods to a retrospective
      cohort based on hospital discharge data in 2001 of Piedmont (north-western Italy)
      residents. RESULTS: Estimated standard errors under the negative binomial for
      both directly and indirectly standardized rates result in almost twice those
      under the Poisson distribution. CONCLUSION: Our analysis confirms that ignoring
      the typical non-random nature of repeated events underestimates the true variance
      of rates and can lead to biased optimistic interpretation of study results.

PMID- 18324938
TI  - Therapeutic approaches to fibromyalgia in the Netherlands: a comparison between
      1998 and 2005.
AB  - RATIONALE: In this study, information was gathered from five disciplines on their
      usual management methods for fibromyalgia (FM) in order to asses whether
      treatment regimens have changed in the Netherlands during a period of 6 years. In
      addition, insight was gained into the therapeutic motives of the professionals.
      METHOD: A questionnaire was sent to a sample of 150 persons per discipline:
      general practitioners (GPs), rheumatologists (RMTs), rehabilitation specialists
      (RS), physical therapists and psychologists. RESULTS: The overall response rate
      was 40.4%. The referral behaviour changed (significantly), especially between GPs
      and RMTs. An increased choice for aerobic exercise (RS: P = 0.023) and
      multidisciplinary therapy (RMT: P = 0.046) was found. RMTs and RS showed
      decreased medication prescribing (RMT: P = 0.024). Preferences of treatment for
      FM differ per discipline. The choice is principally made on the basis of
      subjective, professional group-bound factors. Particularly for GPs, dynamic
      patient factors are an important motive in the management of FM. CONCLUSIONS:
      Despite the fact that most changes found are in conformity with the literature,
      the absolute application percentages of recommended therapies are still very low.
      The differences in practice between the several disciplines seem explicable on
      the basis of the factors that have a prominent role in the choice of a therapy
      for FM. This study underlines the need for further research into methods and
      processes of the management of FM, and their clinical effectiveness. An effective
      way of dissemination, especially of guidelines, is essential.

PMID- 18324939
TI  - Validation of the Chinese version of the MacNew heart disease health-related
      quality of life questionnaire.
AB  - RATIONALE: Patient-reported outcomes such as health-related quality of life
      (HRQL) describe or characterize what patients have experienced as a result of
      their health care. However, treatment outcome comparisons among different pure or
      mixed populations of patients with myocardial infarction, angina or heart failure
      cannot be made using existing coronary heart disease (CHD)-specific HRQL
      instruments. AIMS AND OBJECTIVES: The aim of this study was to evaluate the
      psychometric properties of the Chinese version of the MacNew in a cohort of Hong
      Kong patients diagnosed with CHD. METHODS: Chinese translations of a CHD-specific
      HRQL instrument, the MacNew Heart Disease HRQL questionnaire (MacNew), the Short
      form 36 Health Survey and the Hospital Anxiety and Depression Scale were
      administered to 365 Chinese-speaking patients with CHD at baseline and again 3
      months later (n = 363). The Medical Outcomes Trust Scientific Advisory Committee
      criteria were used to examine the psychometric properties of the Chinese MacNew
      Heart Disease HRQL questionnaire. RESULTS: The results warrant recommending the
      use of the MacNew as an outcome measure to enhance treatment evaluation in
      Chinese patients with CHD and a diagnosis of myocardial infarction, angina or
      heart failure, substantiating previous psychometric data on the MacNew in a
      number of different studies in patients speaking seven different languages.
      CONCLUSION: The MacNew questionnaire may have value as a core CHD questionnaire
      for treatment outcome comparisons among pure or mixed populations of patients
      with myocardial infarction, angina or heart failure.

PMID- 18324940
TI  - Effects of occupational violence on Australian general practitioners' provision
      of home visits and after-hours care: a cross-sectional study.
AB  - RATIONALE, AIMS AND OBJECTIVES: Occupational violence is increasingly recognized
      as a problem in general practice, and has been suggested as adversely affecting
      general practitioners' (GPs) provision of services to patients. The aim of this
      study was to investigate the association of experiences of violence and
      perceptions of risk of violence with provision of after-hours GP care and home
      visits. METHOD: A questionnaire-based cross-sectional survey of GPs in three
      Australian Urban Divisions of General Practice was used. RESULTS: Five hundred
      and twenty-eight GPs completed the survey (response rate 49%). Of the GPs
      surveyed, 63.7% were subjected to some form of violence in the previous 12
      months. Risk of violence influenced 10.2% of GPs' delivery of in-hours home
      visits and 22.0% of GPs' delivery of after-hours home visits. A further 4.7% of
      GPs reported not performing after-hours home visits at all during the previous 12
      months because of safety concerns. On logistic regression, gender, location of
      practice and country of medical qualification were significantly associated with
      provision of in-hours and after-hours home visits. Experience of violence during
      the previous 12 months was not significantly associated with provision of home
      visits. CONCLUSIONS: This study's finding of GPs' self-reported restriction of
      practice and withdrawal from home visits and after-hours calls in response to
      risk of violence represents a significant primary health care issue. GPs'
      decision to provide after-hours calls and home visits is complex, and the finding
      of lack of significant association of experiences of violence with provision of
      home visits and after-hours calls is likely to be due to the cross-sectional
      nature of the study.

PMID- 18324941
TI  - Clinical diagnosis of pneumonia, typical of experts.
AB  - BACKGROUND: Clinical diagnosis of pneumonia is a concern when a patient presents
      with recent cough--new or worsened--together with fever as the chief complaint.
      Given this presentation, the doctor would benefit from having access to software
      that specifies, first, what diagnostic indicators experts typically use in that
      diagnosis; then, upon entry of those facts, what experts' typical probability of
      pneumonia is in such a case; and finally, how much this probability might change
      upon adding the facts from chest radiography. METHODS: We specified a set of 36
      hypothetical presentations of this type by patients 20-70 years of age, involving
      a comprehensive set of clinical-diagnostic indicators. Members of three separate
      expert panels independently set the probability of pneumonia in each of these
      cases, and also the range of possible post-radiography probabilities. A logistic
      function of the diagnostic indicators was fitted to the medians of the
      probabilities. RESULTS: The median probability of pneumonia was a joint function
      of the patient's age and current rate of cigarette smoking; history as to the
      cough's duration, the fever's maximum, dyspnea (including whether on effort only)
      and rigors; and physical examination as to temperature, signs of upper
      respiratory infection, prolongation of expiration, dullness on percussion and
      some auscultation findings. Non-contributory were history of wheezing, pain on
      inspiration, type of sputum and signs of cold or influenza. This probability
      function, and the post-radiography functions based on the same indicators, are
      accessible at http://www.evimed.ch/pneumonia. INTERPRETATION: The expert inputs
      to clinical diagnosis that were derived and made readily accessible provide for
      expertly clinical diagnosis of pneumonia, relevant for decisions about
      radiography and treatment without it.

PMID- 18324942
TI  - Prevalence and type of pre-analytical problems for inpatients samples in
      coagulation laboratory.
AB  - RATIONALE, AIMS AND OBJECTIVES: Total quality in coagulation testing is a
      necessary requisite to achieve clinically reliable results. Evidence was provided
      that poor standardization in the extra-analytical phases of the testing process
      has the greatest influence on test results, though little information is
      available so far on prevalence and type of pre-analytical variability in
      coagulation testing. METHODS: The present study was designed to describe all pre
      analytical problems on inpatients routine and stat samples recorded in our
      coagulation laboratory over a 2-year period and clustered according to their
      source (hospital departments). RESULTS: Overall, pre-analytic problems were
      identified in 5.5% of the specimens. Although the highest frequency was observed
      for paediatric departments, in no case was the comparison of the prevalence among
      the different hospital departments statistically significant. The more frequent
      problems could be referred to samples not received in the laboratory following a
      doctor's order (49.3%), haemolysis (19.5%), clotting (14.2%) and inappropriate
      volume (13.7%). Specimens not received prevailed in the intensive care unit,
      surgical and clinical departments, whereas clotted and haemolysed specimens were
      those most frequently recorded from paediatric and emergency departments,
      respectively. The present investigation demonstrates a high prevalence of pre
      analytical problems affecting samples for coagulation testing. CONCLUSIONS: Full
      implementation of a total quality system, encompassing a systematic error
      tracking system, is a valuable tool to achieve meaningful information on the
      local pre-analytic processes most susceptible to errors, enabling considerations
      on specific responsibilities and providing the ideal basis for an efficient
      feedback within the hospital departments.

PMID- 18324944
TI  - The metabolic syndrome conundrum.

PMID- 18324943
TI  - Safety is part of quality: a proposal for a continuum in performance measurement.
AB  - OBJECTIVES: Safer care is a strategic priority for health care organizations
      worldwide. Yet, the measurement and evaluation of key processes and outcomes
      associated with safer care remains challenging, even with existing performance
      measurement indicators. The multi-national Quality Indicator Project (QI Project)
      data are analysed to [1] document the patterns of safety indicators used between
      1999 and 2006 among hospitals in Asia, Europe and the USA; and [2] to identify
      trends in using both organization-level and patient-level data in hospital
      performance improvement. DESIGN AND SETTING: Retrospective data are used to
      ascertain how the use of safety indicators has changed in comparison to other QI
      Project indicators. 'Continent' rather than 'hospital' is used as the unit of
      analysis and P-values of the differences in use percentages across Asia, Europe
      and the USA are calculated. RESULTS: There was a significant increase in the use
      of QI Project indicators in Asia between 1999 and 2006. Measured as the mean
      percentage of usage, the safety versus 'all other' indicators' increase in Asia
      was 43.7% versus 27% (P < 0.05) and 37.2% versus 24.4% (P < 0.05), respectively,
      during the study's time period. The European participants used both safety and
      all other indicators less frequently, 14.7% versus 18% (P < 0.05) and 9.5% versus
      19.8% (P < 0.05), respectively. Finally, USA hospitals demonstrated a larger
      difference in the decrease of QI Project indicator use than European hospitals
      between the 'safety' and 'all other' indicators, 12.7% decrease for safety
      indicators and 7.1% for all others (P < 0.05). These findings are consistent with
      trends reported in a previous study. CONCLUSION: Traditional performance measures
      continue to assist hospitals in identifying crucial aspects of safety in the
      delivery of care. Building on the findings of a previous study, there are
      emerging trends in the type of measures used in hospitals in Asia, Europe and the
      USA pursuing the improvement of overall performance. The increasing use of
      patient-level data specifically, in tandem with organizational level indicators,
      may signal the continuum of measurement strategies, now still predominantly in
      the USA but anticipated to be adopted both in Europe and Asia.

PMID- 18324945
TI  - Enhanced LDL-C reduction: lower is better. Does it matter how?

PMID- 18324946
TI  - Medical management of intracerebral haemorrhage: back to the basics.

PMID- 18324947
TI  - Could folic acid supplementation in diabetes reduce the risk of cardiovascular
      disease?

PMID- 18324948
TI  - Acute exacerbations in COPD: a real enemy in the natural course of the disease.

PMID- 18324949
TI  - Heart failure is not a diagnosis.
AB  - Heart failure (HF) is a syndrome and not a diagnosis. Aetiology and precipitants
      for decompensation are often not sought. Care is also often based upon protocols,
      with widespread prescription of drugs validated in systolic HF, for patients with
      other forms of HF for example HF with preserved ejection fraction which can
      account for almost half of patients with HF in the UK. Therefore, service design
      and configuration by healthcare providers should based upon quality and not only
      feasibility, as protocol-based treatment will inevitably diminish the quality of
      care for patients with HF and result in both inappropriate care in many cases as
      well as reduced access to advanced evidence based and NICE approved therapies.
      Expertise is therefore of paramount importance in managing patients with HF.

PMID- 18324950
TI  - How to use linear regression and correlation in quantitative method comparison
      studies.
AB  - Linear regression methods try to determine the best linear relationship between
      data points while correlation coefficients assess the association (as opposed to
      agreement) between the two methods. Linear regression and correlation play an
      important part in the interpretation of quantitative method comparison studies.
      Their major strength is that they are widely known and as a result both are
      employed in the vast majority of method comparison studies. While previously
      performed by hand, the availability of statistical packages means that regression
      analysis is usually performed by software packages including MS Excel, with or
      without the software programe Analyze-it as well as by other software packages.
      Such techniques need to be employed in a way that compares the agreement between
      the two methods examined and more importantly, because we are dealing with
      individual patients, whether the degree of agreement is clinically acceptable.
      Despite their use for many years, there is a lot of ignorance about the validity
      as well as the pros and cons of linear regression and correlation techniques.
      This review article describes the types of linear regression and regression
      (parametric and non-parametric methods) and the necessary general and specific
      requirements. The selection of the type of regression depends on where one has
      been trained, the tradition of the laboratory and the availability of adequate
      software.

PMID- 18324951
TI  - A comparison of the effect of alendronate and risedronate on bone mineral density
      in postmenopausal women with osteoporosis: 24-month results from FACTS
      International.
AB  - OBJECTIVES: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg
      OW with respect to change in bone mineral density (BMD), biochemical markers and
      upper gastrointestinal (UGI) tolerability over 24 months. METHODS: This was a 12
      month extension to the Fosamax Actonel Comparison Trial international study
      (FACTS). Postmenopausal women with osteoporosis randomly assigned to either
      alendronate 70 mg OW or risedronate 35 mg OW for the 12-month base study
      continued taking the same double-blind study medication. Efficacy measurements
      were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and
      levels of four bone turnover markers at 24 months. The primary hypothesis was
      that alendronate would produce a greater mean per cent increase from baseline in
      hip trochanter BMD at 24 months. RESULTS: Trochanter BMD increased significantly
      from baseline to month 24 in both groups, with a significantly larger increase
      with alendronate: adjusted mean treatment difference of 1.50% (95% confidence
      interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites.
      Significant geometric mean per cent decreases (p < 0.001) from baseline were seen
      for all four bone turnover markers in both groups, with significantly larger
      decreases (p < 0.001) with alendronate: adjusted mean treatment differences
      ranged from 8.9% to 25.3%. No significant differences were seen in incidence of
      UGI or other adverse events. CONCLUSIONS: Alendronate 70 mg OW yielded
      significantly greater BMD gains and larger decreases in bone turnover marker
      levels than risedronate 35 mg OW over 24 months, with no difference in UGI
      tolerability.

PMID- 18324954
TI  - Severe tricuspid regurgitation presenting with lower limb venous haemorrhage.

PMID- 18324952
TI  - A comparison of the efficacy of darifenacin alone vs. darifenacin plus a
      Behavioural Modification Programme upon the symptoms of overactive bladder.
AB  - PURPOSE: This study assessed the benefit of adding behavioural modification to
      darifenacin treatment for overactive bladder (OAB). MATERIALS AND METHODS: The
      ABLE trial was a randomised, open-label, parallel-group, multicentre study of 12
      weeks of darifenacin treatment [with voluntary up-titration from 7.5 mg once
      daily (qd) to 15 mg qd at week 2] alone or in combination with a Behavioural
      Modification Programme (BMP) for men and women with dry or wet OAB. Efficacy was
      assessed as the change in the number (per day) of micturitions (primary
      variable), urge urinary incontinence (UUI) episodes, urgency episodes, pads used
      and nocturnal voids. Health-related quality of life (HRQoL) was also evaluated.
      Tolerability and safety assessments included adverse events and the number of
      discontinuations. RESULTS: Of 592 patients screened, 395 were randomised, 190 to
      darifenacin alone and 205 to darifenacin + BMP. At baseline, the majority of
      subjects were dry (mean 2.8 and three UUI episodes per day in the darifenacin and
      darifenacin + BMP groups respectively). At study end, darifenacin alone and
      darifenacin + BMP both produced significant reductions from baseline in median
      numbers of micturitions, UUI episodes, urgency episodes and nocturnal voids (all
      p < 0.05), but not in the number of pads used. HRQoL also improved. There were no
      significant differences between treatment groups in efficacy or HRQoL variables.
      CONCLUSIONS: Darifenacin treatment provides a degree of normalisation of
      micturition variables and improvement in HRQoL that cannot be further enhanced by
      behavioural therapy of the type used in this study. Whether behavioural
      modification would add benefit over darifenacin treatment in patients with more
      pronounced incontinence problems remains to be determined.

PMID- 18324955
TI  - Pneumocystis jiroveci (formally carinii) pneumonia in older immunocompromised non
      human immunodeficiency virus (non-HIV) patients: 2 cases and a literature review.

PMID- 18324956
TI  - Management of extended penile trauma with bilateral rupture of cavernosal bodies
      and complete urethral disruption.

PMID- 18324957
TI  - Insulin detemir improves glycaemic control without weight gain in insulin-naive
      patients with type 2 diabetes: subgroup analysis from the PREDICTIVE study.
AB  - OBJECTIVE: Predictable Results and Experience in Diabetes through Intensification
      and Control to Target: an International Variability Evaluation (PREDICTIVE) is a
      multi-national, open-label, prospective, observational study assessing the safety
      and efficacy of insulin detemir in clinical practice. This post hoc subanalysis
      evaluates insulin-naive patients on oral antidiabetic drugs (OADs) who were
      initiated on insulin detemir as basal therapy (+/- OADs). METHODS: The European
      cohort of the PREDICTIVE study currently includes 20,531 patients (12,981 with
      type 2 diabetes) who were prescribed insulin detemir and followed up for 12, 26
      or 52 weeks. Here, we report data from a subgroup of 2377 OAD-treated, insulin
      naive type 2 diabetes patients for a mean follow-up of 14.4 weeks. Patients were
      prescribed insulin detemir as basal therapy (+/- OADs) by their physician, as
      part of routine clinical care. Results were reported in comparison with baseline
      observations. RESULTS: One serious adverse drug reaction was reported, which was
      a major hypoglycaemic episode. Treatment with insulin detemir (+/- OADs)
      significantly reduced mean haemoglobin A(1c) (HbA(1c)) (-1.3%; p < 0.0001),
      fasting glucose (-3.7 mmol/l; p < 0.0001), and within-patient fasting glucose
      variability (-0.5 mmol/l; p < 0.0001). In the majority of patients (82%), these
      improvements in glycaemic control were achieved with once daily administration of
      insulin detemir. There was a small reduction in mean body weight (-0.7 kg; p <
      0.0001), which was most apparent in patients with a higher body mass index (BMI)
      at baseline. A significant negative relationship between weight change and
      baseline BMI was observed (greater the BMI, greater the weight reduction).
      Multiple regression analysis showed that BMI and HbA(1c) at baseline, and change
      in HbA(1c), were all predictors for weight change (p < 0.0001 for all), with BMI
      being the strongest predictor. CONCLUSIONS: Patients with type 2 diabetes naive
      to insulin can be effectively treated with once-daily insulin detemir (+/- OADs)
      to achieve improved glycaemic control with no adverse effect on weight and a low
      risk of hypoglycaemia. These short-term results are consistent with the findings
      of clinical trials.

PMID- 18324958
TI  - Evaluation of three-dimensional changes after sinus floor augmentation with
      different grafting materials.
AB  - OBJECTIVE: The aim of this retrospective investigation was to assess the
      dimensional stability of different grafting materials after maxillary sinus floor
      augmentation with computed tomography (CT) scans. MATERIALS AND METHODS: Two
      postoperative CT scans were available from 16 patients who had undergone
      maxillary sinus lift procedures. The first scan was made within a few days after
      the surgical intervention and the second one >6 months later. A total of 25
      maxillary sinuses were augmented with different materials before implant
      insertion by lateral antrostomy in a staged approach. The volume of bone
      formation was calculated using the Somaris Sienet Magic View software. RESULTS:
      Based on volumetric measurements of the augmented domes derived from the image
      sections, shrinkage was about 26%. The mean of the augmented bone volume was 3.02
      cm(3) (1.4-5.56 cm(3); SD+/-1.18 cm(3)) as determined in the first CT scan. The
      respective mean volume in the second CT scan amounted to 2.28 cm(3) (0.92-4.46
      cm(3); SD+/-1.07 cm(3)). CONCLUSION: Within the limits of our descriptive and
      analytic study, the results indicate a significant reduction of the graft volume
      after maxillary sinus augmentation. Further prospective studies will have to
      evaluate the quantitative changes of different bone graft materials for maxillary
      sinus augmentation procedures in order to improve long-term implant stability.

PMID- 18324959
TI  - In vitro characterization of three-dimensional scaffolds seeded with human bone
      marrow stromal cells for tissue engineered growth of bone: mission impossible? A
      methodological approach.
AB  - AIMS: The aim of the present report was to evaluate current methods of in vitro
      analysis of three-dimensional (3D) scaffolds seeded with human bone marrow
      stromal cells (hBMSCs) from six bone marrow aspirates for tissue engineered
      growth of bone. METHODS: A series of experiments was conducted to compare methods
      of cell expansion and to validate analysis of proliferation and differentiation
      of hBMSCs in long term cultures of up to 40 days in 3D scaffolds of calcium
      carbonate (CaCO(3)) and mineralized collagen. Proliferation within the seeded
      scaffolds was monitored using cell counting, 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl-tetrazolium bromide (MTT), neutral red (NR) and DNA fluorescence assays
      and compared with empty controls. Differentiation was assessed by means of ELISA
      for osteocalcin (OC) and real time PCR for OC and collagen I (Coll I). RESULTS:
      The results showed that the scaffold differed in seeding efficacy (CaCO(3):
      53.3%, min. Coll.: 83.3%). The precise identification of the number of cells in
      biomaterials by MTT, NR and DNA assays was problematic, as MTT and NR assay
      overestimated the number of cells, whereas DNA assay grossly underestimated the
      number of cells on the scaffolds. Monitoring of changes over time may be biased
      by unspecific material-dependent background activity that has to be taken into
      account. Identification of osteogenic differentiation is not reliable by
      identifying osteogenic markers such as OC in the supernatant but has to be done
      on the transcriptional level. CONCLUSIONS: It is concluded that monitoring of in
      vitro procedures for the construction of biohybrid scaffolds requires more
      emphasis in order to make the cell based approach a reliable treatment option in
      tissue engineering.

PMID- 18324960
TI  - Immunohistochemical, tomographic and histological study on onlay iliac grafts
      remodeling.
AB  - The information concerning the molecular events taking place in onlay bone grafts
      are still incipient. The objective of the present study is to correlate the
      effects of perforation of resident bone bed on (1) the timing of onlay autogenous
      graft revascularization; (2) the maintenance of volume/density of the graft
      (assessed through tomography); and (3) the occurrence of bone remodeling proteins
      (using immunohistochemistry technique) delivered in the graft. Thirty-six New
      Zealand White rabbits were subjected to iliac crest onlay bone grafting on both
      sides of the mandible. The bone bed was drill-perforated on one side aiming at
      accelerating revascularization, whereas on the other side it was kept intact.
      After grafts fixation and flaps suture all animals were submitted to tomography
      on both mandible sites. Six animals were sacrificed, respectively, at 3, 5, 7,
      10, 20 and 60 days after surgery. A second tomography was taken just before
      sacrifice. Histological slides were prepared from each grafted site for both
      immunohistochemistry analysis [osteopontin, osteocalcin, type I collagen and
      vascular endothelial growth factor (VEGF) anti-bodies] and histometric analysis.
      The values on bone volume measured on tomography showed no statistic significance
      (P>or=0.05) between perforated and intact sites. Grafts placed on perforated beds
      showed higher bone density values compared with non-perforated ones at 3 days
      (P<or=0.05). This correlation was inverted at 60 days postoperatively. The
      findings from VEGF labeling revealed a tendency for earlier revascularization in
      the perforated group. The early revascularization of bone grafts accelerated the
      bone remodeling process (osteocalcin, type I collagen and osteopontin) that led
      to an increased bone deposition at 10 days. The extended osteoblast
      differentiation process at intermediate stages in the perforated group cooperated
      for a denser bone at 60 days.

PMID- 18324961
TI  - Immunohistochemical characterization of guided bone regeneration at a dehiscence
      type defect using different barrier membranes: an experimental study in dogs.
AB  - OBJECTIVES: The aim of the present study was to evaluate immunohistochemically
      the pattern of guided bone regeneration (GBR) using different types of barrier
      membranes. MATERIAL AND METHODS: Standardized buccal dehiscence defects were
      surgically created following implant bed preparation in 12 beagle dogs. Defects
      were randomly assigned to six different GBR procedures: a collagen-coated bone
      grafting material (BOC) in combination with either a native, three cross-linked,
      a titanium-reinforced collagen membrane, or expanded polytetrafluorethylene
      (ePTFE), or BOC alone. After 1, 2, 4, 6, 9, and 12 weeks of submerged healing,
      dissected blocks were processed for immunohistochemical (osteocalcin - OC,
      transglutaminase II - angiogenesis) and histomorphometrical analysis [e.g., bone
      to-implant contact (BIC), area of new bone fill (BF)]. RESULTS: In general,
      angiogenesis, OC antigen reactivity, and new bone formation mainly arose from
      open bone marrow spaces at the bottom of the defect and invaded the dehiscence
      areas along the implant surface and BOC. At 4 weeks, membranes supporting an
      early transmembraneous angiogenesis also exhibited some localized peripheral
      areas of new bone formation. However, significantly increasing BIC and BF values
      over time were observed in all groups. Membrane exposure after 10-12 weeks was
      associated with a loss of the supporting alveolar bone in the ePTFE group.
      CONCLUSION: Within the limits of the present study, it was concluded that (i)
      angiogenesis plays a crucial role in GBR and (ii) all membranes investigated
      supported bone regeneration on an equivalent level.

PMID- 18324963
TI  - Ehlers-Danlos syndrome--a historical review.
AB  - Ehlers-Danlos syndrome is an inherited heterogeneous group of connective tissue
      disorders, characterized by abnormal collagen synthesis, affecting skin,
      ligaments, joints, blood vessels and other organs. It is one of the oldest known
      causes of bruising and bleeding and was first described by Hipprocrates in 400
      BC. Edvard Ehlers, in 1901, recognized the condition as a distinct entity. In
      1908, Henri-Alexandre Danlos suggested that skin extensibility and fragility were
      the cardinal features of the syndrome. In 1998, Beighton published the
      classification of Ehlers-Danlos syndrome according to the Villefranche nosology.
      From the 1960s the genetic make up was identified. Management of bleeding
      problems associated with Ehlers-Danlos has been slow to progress.

PMID- 18324962
TI  - The non-haematopoietic biological effects of erythropoietin.
AB  - In the haematopoietic system, the principal function of erythropoietin (Epo) is
      the regulation of red blood cell production, mediated by its specific cell
      surface receptor (EpoR). Following the cloning of the Epo gene (EPO) and
      characterization of the selective haematopoietic action of Epo in erythroid
      lineage cells, recombinant Epo forms (epoetin-alfa, epoetin-beta and the long
      acting analogue darbepoetin-alfa) have been widely used for treatment of anaemia
      in chronic kidney disease and chemotherapy-induced anaemia in cancer patients.
      Ubiquitous EpoR expression in non-erythroid cells has been associated with the
      discovery of diverse biological functions for Epo in non-haematopoietic tissues.
      During development, Epo-EpoR signalling is required not only for fetal liver
      erythropoiesis, but also for embryonic angiogenesis and brain development. A
      series of recent studies suggest that endogenous Epo-EpoR signalling contributes
      to wound healing responses, physiological and pathological angiogenesis, and the
      body's innate response to injury in the brain and heart. Epo and its novel
      derivatives have emerged as major tissue-protective cytokines that are being
      investigated in the first human studies involving neurological and cardiovascular
      diseases. This review focuses on the scientific evidence documenting the
      biological effects of Epo in non-haematopoietic tissues and discusses potential
      future applications of Epo and its derivatives in the clinic.

PMID- 18324964
TI  - Chronic lymphocytic leukaemia CD20 expression is dependent on the genetic
      subtype: a study of quantitative flow cytometry and fluorescent in-situ
      hybridization in 510 patients.
AB  - CD20 is an important therapeutic target in chronic lymphocytic leukaemia (CLL).
      In order to examine the relationship between CD20 expression and cytogenetic
      abnormalities, we correlated the fluorescent in-situ hybridization (FISH) genetic
      subtype of 510 treatment-naive patients with CD20 expression as measured by
      quantitative flow cytometry. Patients were classified using the Dohner
      hierarchial classification. The median numbers of CD20 antigen sites by FISH
      subtypes were: 17p- (n = 26), 9341 per cell; 11q- (n = 42), 5886 per cell; +12 (n
      = 93), 23 603 per cell; negative FISH (n = 153), 8828 per cell; and 13q- (n =
      196), 10 781 per cell. Compared to cases with negative FISH, 11q- cases had
      significantly lower CD20 expression (P = 0.001), and +12 cases had significantly
      higher CD20 expression (P < 0.001). The significance of trisomy 12 and high CD20
      expression was maintained after multivariate analysis accounting for other
      disease characteristics. Fifty-nine patients received the combination of
      rituximab and granulocyte-macrophage colony-stimulating factor as frontline
      therapy; responses were observed in 13 of 14 (93%) patients with +12, in two of
      four (50%) patients with 11q-, and in 30 of 41 (73%) patients with negative FISH,
      13q- or 17p- CLL. Leukemic CD20 expression differed significantly between FISH
      subtypes. Patients with trisomy 12 CLL showed strong leukemic cell CD20
      expression and had a high rate of response to rituximab-based therapy.

PMID- 18324965
TI  - Alternate day pomalidomide retains anti-myeloma effect with reduced adverse
      events and evidence of in vivo immunomodulation.
AB  - We previously reported that daily dose pomalidomide (CC-4047), a thalidomide
      analogue, has excellent anti-myeloma activity but is associated with
      myelosuppression and deep vein thrombosis. We report here a phase 1 study to
      determine the maximum tolerated dose (MTD) of pomalidomide at 1 mg, 2 mg, 5 mg
      and 10 mg on alternate days (ad). Twenty patients with relapsed myeloma were
      treated. Grade 4 neutropenia occurred in all patients receiving 10 mg and the MTD
      was defined as 5 mg ad. No thrombotic events were observed. Pomalidomide was
      continued following the 4-week MTD study in 17/20 patients for a median of 14
      months. 10% of patients had a complete response and >50% reduction in paraprotein
      was achieved in 50% of subjects. Progression-free survival was 10.5 months and
      median overall survival was 33 months. A significant rise was observed in the
      proportion of CD8(+) cells. Alternate day pomalidomide was associated with a
      marked reduction in the incidence of thrombosis whilst maintaining excellent anti
      myeloma activity. This trial provides further in vivo evidence that pomalidomide
      modulates the immune system in myeloma patients. Phase 2 studies to further
      assess the optimal schedule of administration and anti-myeloma activity of this
      agent are planned.

PMID- 18324966
TI  - Therapy-associated genetic aberrations in patients treated for non-Hodgkin
      lymphoma.
AB  - Therapy-associated myelodysplastic syndromes and acute myeloid leukaemia (t
      AML/MDS) following high dose chemotherapy are significant problems, with a
      cumulative incidence of 20% or more in myeloablative treatment regimen.
      Retrospective findings indicated that t-AML/MDS associated genetic aberrations
      can be observed directly after exposure to chemotherapy and can precede t-AML by
      several months. To determine the incidence of post-therapeutic aberrations and
      their predictive value, we prospectively investigated 316 samples of 95 patients
      with non-Hodgkin lymphoma (NHL) who were treated with intermediate and high dose
      chemotherapy (Arm A and B of the megaCHOEP (cyclophosphamide, doxorubicin,
      etoposide, vincristine, prednisolone) trial of the German High Grade NHL study
      group). Molecular aberrations (RUNX1/RUNX1T1, PML-RARA, CBFB-MYH11, MLL-MLLT1,
      BCR-ABL1) were observed in 33.3% (Arm A) and 55.4% (Arm B) of patients and in
      14.9% and 28.7% of respective samples. Cytogenetic analysis of 53 NHL patients
      after high dose therapy showed frequent chromosomal breakage. Clonal aberrations
      were found in three patients. None of these patients developed a t-AML/MDS during
      a 3-year clinical follow up period. We concluded that the high incidence of
      genetic aberrations reflected a dose-dependent, transient therapy-induced genetic
      damage which is not predictive of a t-AML/MDS.

PMID- 18324967
TI  - Magnetic resonance imaging for the detection of bone marrow involvement in
      malignant lymphoma.
AB  - This study systematically reviewed the published data regarding the sensitivity
      of magnetic resonance imaging (MRI) compared with bone marrow biopsy as reference
      standard for the detection of bone marrow involvement in patients with malignant
      lymphoma. A systematic search for relevant studies was performed of the
      PubMed/MEDLINE and Embase databases. Two reviewers independently assessed the
      methodological quality of each study and the sensitivity of the included studies
      was calculated. The 11 included studies had moderate methodological quality.
      Sensitivity of MRI for the detection of bone marrow involvement ranged from 50%
      to 100%, with a median of 100%. MRI is probably sufficiently sensitive to rule
      out bone marrow involvement in patients with malignant lymphoma. However, a well
      designed study with a large sample size is needed to confirm current results.

PMID- 18324968
TI  - Expression of the human germinal-centre-associated lymphoma protein in diffuse
      large B-cell lymphomas in patients with rheumatoid arthritis.
AB  - Diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal centre
      (GC)-like and non-GC-like subtypes by CD10, BCL6 and MUM1/IRF4 status. We
      previously reported that patients with severe rheumatoid arthritis (RA) are at
      increased risk of non-GC DLBCL. This study examined a new GC-marker, human
      germinal-centre-associated lymphoma (HGAL) protein, in RA-DLBCL. Of 111, 38 (34%)
      DLBCL were HGAL-positive and showed less disseminated disease and a tendency
      toward improved overall survival compared to HGAL-negative cases. This supports
      that a majority of RA-DLBCL are of non-GC origin, indicating a specific role for
      activated peripheral B cells in the pathogenesis of RA-DLBCL.

PMID- 18324969
TI  - Adverse outcomes of blood transfusion in children: analysis of UK reports to the
      serious hazards of transfusion scheme 1996-2005.
AB  - Between 1996 and 2005 the Serious Hazards of Transfusion (SHOT) scheme analysed
      3239 reports of adverse reactions and events associated with transfusion of
      labile blood components in the UK. 321 reports (10%) related to transfusion of
      children under 18 years and 147/3239 (4.5%) to infants less than 12 months of
      age. There were 264 cases in children of 'incorrect blood component transfused',
      resulting from errors at all stages in the transfusion chain; 26/264 suffered
      actual or potential morbidity. Thirty acute transfusion reactions, three delayed
      transfusion reactions, 20 cases (three fatal) of transfusion-related acute lung
      injury, two cases (both fatal) of transfusion-associated graft-versus-host
      disease and two transfusion transmitted infections were reported. A population
      based epidemiological study of transfused patients in 2004 showed that 4.2% of
      red cells are transfused to patients less than 18 years and 1.7% to infants less
      than 12 months. Interpretation of SHOT data against this context enabled the
      estimation of the incidence of an adverse outcome to be 18:100,000 red cells
      issued for children less than 18 years and 37:100,000 for infants less than 12
      months, compared to 13:100,000 for adults. Adherence to relevant guidelines,
      knowledge of specialist transfusion needs of children and good communication are
      essential if this risk is to be reduced.

PMID- 18324970
TI  - Effects of extensive splenomegaly in patients with myelofibrosis undergoing a
      reduced intensity allogeneic stem cell transplantation.
AB  - Changes in spleen size postallogeneic haematopoietic stem cell transplantation
      (HSCT) in patients with primary myelofibrosis have been poorly characterized. We
      analysed 10 patients with myelofibrosis and splenomegaly following a reduced
      intensity allogeneic HSCT. All patients fully engrafted donor cells including
      five patients with extensive splenomegaly. Extensive splenomegaly was associated
      with a prolonged time to neutrophil and platelet recovery. In all 10 patients, a
      progressive reduction of splenomegaly was documented within 12 months post
      transplant and paralleled the reduction of marrow fibrosis. These findings
      suggest that myelofibrosis patients with extensive splenomegaly may proceed with
      allogeneic HSCT without prior splenectomy.

PMID- 18324971
TI  - Loss of phospholipid membrane asymmetry and sialylated glycoconjugates from
      erythrocyte surface in haemoglobin E beta-thalassaemia.
AB  - This study aimed to investigate any correlation between the extent of
      phosphatidylserine (PS) asymmetry and sialylated glycoconjugate levels with the
      faster clearance of circulating erythrocytes in haemoglobin E (HbE) beta
      thalassaemia. Erythrocytes from peripheral blood samples of different HbEbeta
      thalassaemia patients showed loss of PS asymmetry measured by annexin V binding
      using flow cytometry. Maximum PS exposure was found when HbE was 50-60% and HbF
      was <20% indicating a possible correlation with severity of the disease.
      Separation of erythrocytes into aged and younger cells showed higher loss of PS
      asymmetry in the younger erythrocytes of HbEbeta-thalassaemia patients when
      compared with normal blood, where PS asymmetry was lost only in the older cells.
      Sialylated glycoconjugate measurement using the lectins wheatgerm agglutinin and
      pokeweed mitogen showed loss of sialic acid and N-acetyl-D-glucosamine-bearing
      glycoproteins in the order normal<homozygous E<HbEbeta-thalassaemic upon ageing.
      A possible correlation was found between the loss of PS asymmetry with HbE level
      and the reduction of glycophorins from the cell surface, mediated by membrane
      vesiculation. A more facilitated vesiculation process in HbEbeta-thalassaemic
      erythrocytes could lead to faster shedding of glycophorin-containing
      microvesicles, leaving highly PS-exposed erythrocytes accessible to phagocytes.

PMID- 18324972
TI  - Increased CD177 (PRV1) expression in thalassaemia and the underlying
      erythropoietic activity.
AB  - CD177 (PRV1) expression is strongly related to polycythaemia vera (PV). Whilst
      studying CD177 expression in PV patients and controls, individuals with beta
      thalassaemia minor were found to display an elevated expression of CD177. The
      study was expanded to include patients with thalassaemia intermedia, sickle
      cell/beta-thalassaemia and thalassaemia major. CD177 expression was increased in
      these thalassaemic groups and correlated with their erythropoietic activity, as
      assessed by the measurement of serum erythropoietin and soluble transferrin
      receptor levels. Within this context, elevated CD177 expression is not only a
      specific feature of PV but may be an indicator of increased erythropoietic
      activity in thalassaemia syndromes.

PMID- 18324973
TI  - beta(2)-Adrenergic receptor and adenylate cyclase gene polymorphisms affect
      sickle red cell adhesion.
AB  - Sickle red cell (SS RBC) adhesion is thought to contribute to sickle cell disease
      (SCD) pathophysiology. SS RBC adhesion to laminin increases in response to
      adrenaline stimulation of beta(2)-adrenergic receptors (beta(2)ARs) and adenylate
      cyclase (ADCY6), and previous evidence suggests such activation occurs in vivo.
      We explored whether polymorphisms of the beta(2)AR and ADCY6 genes (ADRB2 and
      ADCY6, respectively) affect RBC adhesion to laminin. We found that the beta(2)AR
      arg(16)-->gly substitution and two non-coding ADCY6 polymorphisms were associated
      with elevated adhesion. We postulate that ADRB2 and ADCY6 polymorphisms may
      influence SCD severity through the mechanism of RBC adhesion.

PMID- 18324974
TI  - 'Precursors' of classical Hodgkin lymphoma in samples of angioimmunoblastic T
      cell lymphoma.

PMID- 18324975
TI  - Clinical effectiveness of decitabine in severe sickle cell disease.

PMID- 18324976
TI  - The AJT report.
AB  - With the new drug approval rate at a 25-year low, critics of the FDA contend that
      the agency is infringing on the transplant community's standard of care. AJT
      takes an in-depth look.

PMID- 18324977
TI  - Open letter to the FDA: new drug trials must be relevant.

PMID- 18324978
TI  - Smoking after cardiac transplantation.
AB  - Although smoking cessation is a prerequisite prior to listing for cardiac
      transplantation, some patients return to smoking after recovery. We have covertly
      assessed the smoking habits of our cardiac transplant recipients (with ethical
      approval) since 1993 by measuring urinary cotinine: a level of >500 ng/mL
      signifying continued tobacco use. We retrospectively analyzed survival, causes of
      death and the development of graft coronary artery disease (GCAD) with respect to
      the number of positive and negative cotinine levels. One hundred four of 380
      (27.4%) patients tested positive for active smoking at some point posttransplant,
      and 57 (15.0%) tested positive repeatedly. Smokers suffered significantly more
      deaths due to GCAD (21.2% vs. 12.3%, p < 0.05), and due to malignancy (16.3% vs.
      5.8%, p < 0.001). In univariate analysis, smoking after heart transplantation
      shortened median survival from 16.28 years to 11.89 years. After correcting for
      the effects of pretransplant smoking in time-dependent multivariate analysis,
      posttransplant smoking remained the most significant determinant of overall
      mortality (p < 0.00001). We conclude that tobacco smoking after cardiac
      transplantation significantly impacts survival by accelerating the development of
      graft vasculopathy and malignancy. We hope that this information will deter
      cardiac transplant recipients from relapsing, and intensify efforts in improving
      cessation rates.

PMID- 18324979
TI  - Increasing organ donations after cardiac death by increasing DCD support among
      health care professionals: a case report.
AB  - This case report focuses on the University of Wisconsin Hospital and Clinics
      Organ Procurement Organization (UWHC-OPO) efforts to produce a verifiable and
      demonstrable increase in organ donations by developing a replicable, transferable
      and feasible model intervention for increasing health care professionals' support
      for donation after cardiac death (DCD). A grant from the US Department of Health
      and Human Services funded a 3-year study allowing the UWHC-OPO to (i) identify
      barriers to and opportunities for increasing DCD support among those involved in
      the donation request process, (ii) implement this better understanding of these
      support factors in the creation of intervention materials designed to increase
      knowledge of and support for DCD and finally (iii) to track and document the
      progress made in increasing knowledge, support, number of hospitals with DCD
      protocols, actual requests made and number of DCD donors. The results of the
      model intervention were extremely positive, showing lasting increases in DCD
      knowledge and support, adoption of DCD protocols and referrals in the two
      tracking survey stages following the intervention. Perhaps most notably, DCD
      donor numbers within the UWHC-OPO region increased 93% in the year following the
      intervention and 179% to date.

PMID- 18324980
TI  - Valuing and empowering nurses.

PMID- 18324981
TI  - Job stress, recognition, job performance and intention to stay at work among
      Jordanian hospital nurses.
AB  - PURPOSE: To investigate: (1) relationships between job stress, recognition of
      nurses' performance, job performance and intention to stay among hospital nurses;
      and (2) the buffering effect of recognition of staff performance on the 'stress
      intention to stay at work' relationship. BACKGROUND: Workplace stress
      tremendously affects today's workforce. Recognition of nurses' performance needs
      further investigation to determine if it enhances the level of intention to stay
      at work and if it can buffer the negative effects of stress on nurses' intention
      to stay at work. DESIGN AND METHODS: The sample of the present study was a
      convenience one. It consisted of 206 Jordanian staff nurses who completed a
      structured questionnaire. RESULTS: The findings of the study indicated a direct
      and a buffering effect of recognition of nurses' performance on job stress and
      the level of intention to stay at work. CONCLUSION: The results of the study
      indicated the importance of recognition for outstanding performance as well as
      achievements. Implications for nursing management The results of this study
      support the need to focus on the implementation of recognition strategies in the
      workplace to reduce job stress and enhance retention.

PMID- 18324982
TI  - Voluntary turnover among nurses working in Kuwaiti hospitals.
AB  - BACKGROUND: Voluntary turnover rates are high among staff nurses working in
      Kuwaiti hospitals. It is a major problem, costly and it is presumed to impact on
      the quality of nursing care delivered. AIMS: The two aims of this study were to
      (1) find out if nurses' resignations in Kuwaiti hospitals could be ascribed to
      failure in the recruitment process and (2) examine the feelings of nurses who
      resigned. METHODS: Two sets of exit interviews with 60 nurses who had resigned
      were conducted. RESULTS: No evidence emerged that any false information or
      misleading information was provided except for the salary adjustments. The real
      insight lay in what might not have been said in the recruitment interviews. While
      feelings of discontent emerged in the interviews relating to the loss of income,
      the greatest source of complaint related to the failure of managers to solve the
      evident problems. CONCLUSIONS: High rates of voluntary turnover require more
      attention from administrators and policy makers because of its potential
      consequences in terms of the quality of nursing care delivered. Implications for
      nursing management This paper identifies many causes of nurses' voluntary
      turnover. It also shows the need for nursing managers to explore these causes and
      suggests successful strategies for recruitment and retention practices and
      policies.

PMID- 18324983
TI  - Predictors of career commitment and job performance of Jordanian nurses.
AB  - BACKGROUND AND AIMS: Few studies focused on nurses' career commitment and nurses'
      job performance. This research aimed at studying variables of nurses' career
      commitment and job performance, and assessing the relationship between the two
      concepts as well as their predictors. METHODS: A survey was used to collect data
      from a convenient sample of 640 Registered Nurses employed in 24 hospitals.
      RESULTS: Nurses 'agreed' to be committed to their careers and they were
      performing their jobs 'well'. As a part of career commitment, nurses were willing
      to be involved, in their own time, in projects that would benefit patient care.
      The highest and lowest means of nurses' job performance were reported for the
      following aspects: leadership, critical care, teaching/collaboration,
      planning/evaluation, interpersonal relations/communications and professional
      development. Correlating of total scores of nurses' career commitment and job
      performance revealed the presence of a significant and positive relationship
      between the two concepts. Stepwise regression models revealed that the explained
      variance in nurses' career commitment was 23.9% and that in nurses' job
      performance was 29.9%. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers should
      promote nursing as a career and they should develop and implement various
      strategies to increase nurses' career commitment and nurses' job performance.
      These strategies should focus on nurse retention, staff development and quality
      of care. CONCLUSIONS: Nurses' career commitment and job performance are inter
      related complex concepts that require further studies to understand, promote and
      maintain these positive factors in work environments.

PMID- 18324984
TI  - Change process during redesign of a model of nursing practice in a surgical ward.
AB  - AIM: This paper reports a case study of nursing practice model redesign in a
      surgical ward at a large metropolitan acute care hospital in Sydney, Australia.
      BACKGROUND: Literature suggests that factors such as financial restraints and
      shortage of nurses necessitate redesign of nursing care. METHOD: A descriptive
      case study design was used. The nursing practice model was changed from a patient
      allocation model to a team-nursing model and a new role of Clinical Activities
      Coordinator was introduced. RESULTS: This study has confirmed that people need to
      be able to empower themselves to ensure an effective change process. It was also
      apparent in the case study that the staff were resistant to the redesign.
      CONCLUSIONS: Change is a difficult process, which needs to involve all
      stakeholders. The planning process needs to consider the characteristics of the
      context such as workload and skill required, and the measures such as patient and
      staff satisfaction and health outcomes.

PMID- 18324985
TI  - Organizational factors that support the implementation of a nursing best practice
      guideline.
AB  - BACKGROUND: The context of the healthcare setting may play a crucial role in
      influencing the implementation of best practice guidelines in nursing. Further
      study is required to understand these organizational factors. Two variables,
      organizational culture and leadership, are thought to influence the adoption of
      best practice guidelines. AIM: A discussion of organizational factors that
      influence best practice guideline adoption is presented. A small pilot study is
      provided as an example of methods for further research. METHODS: A quantitative
      survey of nursing staff was conducted. RESULTS: Results from the pilot study
      reveal variability in best practice guideline implementation despite the presence
      of a culture of organizational learning and transformational leadership.
      CONCLUSIONS: There is beginning evidence in the literature that culture and
      leadership are key elements influencing guideline implementation. In this pilot
      work on two inpatient units where a nursing best practice guideline was
      implemented, a supportive organizational culture and key people leading change
      were present. Implications for further studies are offered. IMPLICATIONS FOR
      NURSING MANAGEMENT: Nursing leaders interested in promoting the use of best
      practice guidelines must pay attention to the organizational context in which
      nursing care occurs. A supportive culture where learning is valued coupled with
      transformational leadership may be key factors in the implementation and the
      sustainability of best practice guidelines.

PMID- 18324986
TI  - Implementation of a documentation model comprising nursing terminologies-
      theoretical and methodological issues.
AB  - AIMS: To describe and discuss theoretical and methodological issues of
      implementation of a nursing services documentation model comprising NANDA nursing
      diagnoses, Nursing Intervention Classification and Nursing Outcome Classification
      terminologies. BACKGROUND: The model is developed for electronic patient record
      and was implemented in a psychiatric hospital on an organizational level and on
      five test wards in 2001-2005. METHODS: The theory of Rogers guided the process of
      innovation, whereas the implementation procedure of McCloskey and Bulecheck
      combined with adult learning principals guided the test site implementation.
      RESULTS: The test wards managed in different degrees to adopt the model. Two
      wards succeeded fully, including a ward with high percentage of staff with
      interdisciplinary background. CONCLUSIONS: Better planning regarding the impact
      of the organization's innovative aptitude, the innovation strategies and the use
      of differentiated methods regarding the clinician's individual premises for
      learning nursing terminologies might have enhanced the adoption to the model.
      IMPLICATIONS FOR NURSING MANAGEMENT: To better understand the nature of barriers
      and the importance of careful planning regarding the implementation of electronic
      patient record elements in nursing care services, focusing on nursing
      terminologies. Further to indicate how a theory and specific procedure can be
      used to guide the process of implementation throughout the different levels of
      management.

PMID- 18324987
TI  - Strategies for assessing the feasibility to develop new needs-oriented services
      by public health nurses.
AB  - AIM: To explore the strategies that public health nurses use to assess the
      feasibility of creating new services. BACKGROUND: Although creating a needs
      oriented service is a core competency of public health nurses, the practical
      approaches taken to assess the feasibility of developing new projects are
      unclear. DESIGN: Ten Japanese public health nurses were interviewed using Yin's
      Case Study Method. FINDINGS: The public health nurses employed common strategies
      to assess the feasibility of new projects regardless of differences in their
      experience and the services: 'Estimating the impact of a new project',
      'Predicting the resources necessary to implement a new service and quantifying
      their availability', 'Looking for a promoter of the anticipated project',
      'Facilitating recognition of public health nursing practice by the unit head and
      colleagues' and 'Understanding the intentions of the unit head and co-workers
      with regard to developing a new service'. CONCLUSION: These identified empirical
      strategies facilitate the establishment of new needs-oriented projects by public
      health nurses. IMPLICATIONS FOR NURSING MANAGEMENT: The new strategies and the
      model contributed to improving the effectiveness and efficiency of developing a
      new service by public health nurses at different levels of experience.

PMID- 18324988
TI  - Complexity science and participation in decision making among Taiwanese nurses.
AB  - AIM: The perspective of interconnection in complexity science is used to examine
      the concept of participation in decision making among Taiwanese nurses in the
      context of Chinese communication culture. BACKGROUND: Participation in decision
      making among nurses has been widely discussed and tested in the Western
      healthcare systems. Many studies have shown that participation in decision making
      relates to nurses' autonomy, job satisfaction and quality of care. However,
      participation in decision making has not been fully discussed in Taiwan's nursing
      community. In a different cultural environment, participation in decision making
      may have different effects. EVALUATION: The concept of participation in decision
      making is analysed in three facets of Chinese communication culture: (1)
      hierarchical social relationship; (2) harmony maintenance; and (3) insider
      effects. Key issues Taiwanese nurses might establish different levels of
      participation and need to use different strategies to enhance participation in
      decision making for desired outcomes. CONCLUSION: While applying participation in
      decision making in a different context, it is very important to consider the
      social and cultural differences. IMPLICATIONS FOR NURSING MANAGEMENT: Two
      implications are made. First, nursing leaders/managers who are working with a
      multicultural team should be aware of the cultural difference in the pattern of
      interaction in the process of participation in decision making. Second,
      leaders/managers should be creative and try to apply different strategies to
      encourage staff's participation in decision making.

PMID- 18324989
TI  - Using simplified Chaos Theory to manage nursing services.
AB  - AIMS: The purpose of this study was to evaluate the part simplified chaos theory
      could play in the management of nursing services. BACKGROUND: As nursing care
      becomes more complex, practitioners need to become familiar with business
      planning and objective time management. There are many time-limited methods that
      facilitate this type of planning but few that can help practitioners to forecast
      the end-point outcome of the service they deliver. METHODS: A growth model was
      applied to a specialist service to plot service trajectory. RESULTS: Components
      of chaos theory can play a role in forecasting service outcomes and consequently
      the impact upon the management of such services. IMPLICATIONS FOR NURSING
      MANAGEMENT: The ability to (1) track the trajectory of a service and (2)
      manipulate that trajectory by introducing new variables can allow managers to
      forward plan for service development and to evaluate the effectiveness of a
      service by plotting its end-point state.

PMID- 18324990
TI  - Predictors of nurses' perceptions of barriers to research utilization.
AB  - AIM: To identify predictors of nurses' self-reported barriers to using research
      findings in clinical practice. BACKGROUND: Several studies have shown that nurses
      perceive barriers to research utilization but to our knowledge predictors of
      nurses perceptions of barriers to research utilization have not been identified
      before. METHODS: Three questionnaires were answered by 833 nurses: the Barriers
      Scale, the Quality Work Competence questionnaire and a questionnaire including
      questions on professional issues. RESULTS: Dissatisfaction with support from
      immediate superiors for participating in research and/or development projects,
      having no academic degree and unclear and unrealistic workplace goals were
      identified as factors increasing the risk of perceiving barriers to the use of
      research findings in clinical practice. CONCLUSIONS: The results imply that head
      nurses, nursing managers and other health care leaders should create strategies
      for supporting nurses' professional development and possibilities to implement
      research findings in clinical practice. IMPLICATIONS FOR NURSING MANAGEMENT: To
      support research utilization and evidence-based care health care leaders, head
      nurses and nurse managers should create clear and realistic goals for the work
      place including demands on evidence-based care. It is also important for head
      nurses and nurse managers to create strategies for supporting nurses'
      professional development and possibilities to implement research findings in
      clinical practice.

PMID- 18324991
TI  - Stakeholders' perceptions of a research capacity development project for nurses,
      midwives and allied health professionals.
AB  - AIMS: To evaluate stakeholders perceptions of the extent to which a research
      facilitator post was addressing aims of: * providing academic support to enable
      research involvement of nurses, midwives and allied health professionals; *
      supporting dissemination of research into practice; * contributing to research
      strategy development. BACKGROUND: Barriers to research capacity development have
      been recognized for nurses, midwives and allied health professionals. A project
      established in a London NHS trust aimed to address these. METHODS: A mixed
      methods approach was used. RESULTS: Responses were generally very positive. The
      post effected improvements in the research culture and perceived increase in
      research-related activities. CONCLUSION: The post made substantial progress
      towards its aims. This approach may be useful in other healthcare locations to
      build research capacity. IMPLICATIONS FOR NURSING MANAGEMENT: Challenged by
      increasing priority accorded to research capacity and service research
      implementation yet recognition of barriers to achievement, this study offers
      insights from one means to address this.

PMID- 18324992
TI  - Increasing research evidence in practice: a possible role for the consultant
      nurse.
AB  - AIMS: To determine the extent to which clinical nursing practice has adopted
      research evidence. To identify barriers to the application of research findings
      in practice and to propose ways of overcoming these barriers. BACKGROUND: Way
      back in 1976, nursing and midwifery practice started adopting research evidence.
      By 1990s, there was some transparency of research evidence in practice, but more
      could have been done to widen its adoption. Many barriers were identified which
      could hinder implementation of the evidence in practice, and the effort to remove
      these remains weak. EVALUATION: 25 research articles from across Europe and
      America were selected, and scrutinized, and recommendations analysed. FINDINGS:
      Many clinical practitioners report a lack of time, ability and motivation to
      appraise research reports and adopt findings in practice. The clinical
      environment was not seen as research friendly as there were a general lack of
      research activities and facilities locally. There was a clear lack of research
      leadership in practice. IMPLICATION FOR NURSING MANAGEMENT: This paper reviewed
      the research evidence from several published research papers and provides
      consultant nurses with practical suggestions on how to enhance research evidence
      application in their practice. It recommends how consultant nurses can make their
      practice more research transparent by providing the required leadership, creating
      a research-friendly organization, developing a clear research agenda and
      facilitating staff develop a local research framework for reading research and
      implementing research evidence in their practice.

PMID- 18324993
TI  - Examining the knowledge, attitude and use of research by nurses.
AB  - AIM: This study sought to determine the knowledge, attitudes and use of research
      by nurses. BACKGROUND: There is little evidence about whether nurses are aware of
      using research and how much research they use in their clinical practice. METHOD:
      Using a descriptive design, 347 registered and Enrolled Nurses completed the
      Edmonton Research Orientation Survey. RESULTS: Senior Nurse Managers were more
      likely to have a positive attitude towards research, and completion of university
      subjects on nursing research was significant in determining attitude and
      knowledge of research. All nurses, regardless of position identified barriers to
      performing research. CONCLUSION: Nurses require specific research education,
      clinical nursing leadership and work environments conducive to ensure practice is
      evidenced-based. IMPLICATIONS FOR NURSING MANAGEMENT: A positive attitude towards
      research by Senior Nurse Managers has the potential to influence other nurses in
      establishing an active nursing research culture and promote evidence-based
      practice in the workplace.

PMID- 18324994
TI  - Driving towards an improved research and development culture.
AB  - BACKGROUND: This study examined the research and development culture and capacity
      within one NHS Trust in Northern Ireland. Strengths and challenges were
      identified and opportunities for further research and development expansion were
      sought. METHODS: This is a two-stage project incorporating a baseline survey (n =
      379) followed by consultation with key stakeholders across the Trust (n = 11).
      FINDINGS: In the survey, over half of the respondents (n = 194) stated they had
      participated in a research project and a significant number (n = 313) read health
      care journals. Identification of barriers to research resulted in findings
      similar to other published work. Staff responded positively about using research
      in practice (n = 328) and that practice should be influenced by research (n =
      312). Nurse Managers indicated support for research and development activity.
      CONCLUSION: The study provides a starting point from which to develop a positive
      research and development culture within this Trust. IMPLICATIONS FOR NURSING
      MANAGEMENT: After establishing a baseline of research and development activity
      across a large acute Trust, the strengths and weaknesses of such activity were
      identified with a view to informing a strategy to develop this aspect of
      professional activity. A change in an organizational culture cannot be made
      without full support of both the clinicians and their managers.

PMID- 18324995
TI  - Managing nurses through disciplinary power: a Foucauldian analysis of workplace
      violence.
AB  - AIMS: This paper describes discipline as a specific technique of power which
      constitutes, in our view, a form of institutional violence. BACKGROUND: The need
      to create and maintain safe and healthy work environments for healthcare
      professionals is well documented. EVALUATION: Foucault's concept of disciplinary
      power was used to explore institutional violence from a critical perspective. KEY
      ISSUE: Violence is identified as an important factor in the recruitment and
      retention of healthcare professionals. Given the shortage of such professionals,
      there is an urgent need to take a fresh look at their working environments and
      working conditions. CONCLUSION: Power, surveillance and disciplinary techniques
      are used at all levels of hospital management to control and contain both human
      resources and costs. IMPLICATIONS FOR NURSING MANAGEMENT: By associating common
      workplace practices with institutional violence, employers who have a policy of
      zero tolerance toward workplace violence will need to re-examine their current
      ways of operating.

PMID- 18324996
TI  - Determinants of moral distress in medical and surgical nurses at an adult acute
      tertiary care hospital.
AB  - AIM: To determine the prevalence and contributing factors of moral distress in
      medical and surgical nurses. BACKGROUND: Moral distress from ethical conflicts in
      the work environment is associated with burnout and job turnovers in nurses.
      METHOD: A prospective cross-sectional survey using the Moral Distress Scale tool
      was administered to medical and surgical nurses at an adult acute tertiary care
      hospital. RESULTS: The survey was completed by 260 nurses (92% response rate).
      The intensity of moral distress was uniformly high to situations related to
      physician practice, nursing practice, institutional factors, futile care,
      deception and euthanasia. Encounter frequencies for situations associated with
      futile care and deceptions were particularly high. Encounter frequencies
      increased with years of nursing experience and caring for oncology and transplant
      patients. CONCLUSION: Moral distress is common among nurses in acute medical and
      surgical units and can be elicited from different types of situations encountered
      in the work environment. Nursing experience exacerbated the intensity and
      frequency of moral distress. IMPLICATIONS FOR NURSING MANAGEMENT: Strategies
      aimed to minimize exposure to situations of moral distress and augment mechanisms
      mitigating its effect on nurses are necessary to enhance job satisfaction and
      retention.

PMID- 18324997
TI  - Nurse executive director effectiveness: a systematic review of the literature.
AB  - AIM: This report systematically reviews studies of nurse executive director
      effectiveness to identify recurring themes that might inform current practice and
      future research. BACKGROUND: Increasing competition in healthcare markets is
      increasing the demands on nurse executive directors. There is a need to identify
      factors that contribute to effectiveness in the role so that these can be
      developed and effectiveness improved. EVALUATION: Reports were identified using
      electronic databases, an internet search and review of references in all reports
      initially identified. The methodology of these reports was reviewed and recurring
      themes were identified. KEY ISSUES: Ten themes that might be associated with
      nurse executive director effectiveness emerged from the review. CONCLUSIONS: The
      literature relating to nurse executive director effectiveness is limited but
      there are sufficient recurring themes to inform current practice and to
      investigate in new research.

PMID- 18324999
TI  - In response to: Curtis L. and Netten A. (2007) The costs of training a nurse
      practitioner in primary care: the importance of allowing for the cost of
      education and training when making decisions about changing the professional-mix.
      Journal of Nursing Management 15, 449-457.

PMID- 18325000
TI  - Porcine luteal function in relation to IGF-1 levels following ovulation during
      lactation or after weaning.
AB  - This study presents relationships between peripheral progesterone and Insulin
      like Growth Factor-1 (IGF-1) concentrations during the early luteal phase in
      sows. Data were derived from three experiments, one with primiparous weaned sows
      (n = 21) and two with multiparous sows that either ovulated during lactation (n =
      23) or after weaning (n = 12). The sows that ovulated during lactation did so due
      to an intermittent suckling regime (inhibition of suckling for 12 h each day from
      day 14 of lactation) or due to treatment with PG600. IGF-1 concentrations varied
      considerably among experiments, and were the lowest in the multiparous sows,
      regardless of whether they were weaned or lactating: 68 +/- 5 and 85 +/- 8 ng/ml
      in the two experiments with multiparous sows vs 188 +/- 15 ng/ml in the
      primiparous sows. Progesterone concentrations were lowest for the lactating sows.
      Overall, the increase in progesterone during the early luteal phase was strongly
      correlated with IGF-1 concentrations (r = 0.7). However, the correlation was low
      in multiparous lactating sows (r = 0.28; p < 0.10) and nonsignificant in
      multiparous weaned sows (r = 0). The weaned multiparous sows had IGF-1 levels
      comparable to lactating multiparous sows, but higher progesterone levels. In
      conclusion, these data show a positive relationship between peripheral IGF-1 and
      progesterone concentrations in vivo during the early luteal phase. In lactating
      sows, IGF-1 concentrations are probably a limiting factor for progesterone
      secretion, although other factors may be involved.

PMID- 18325001
TI  - Noradrenergic control of arginine vasopressin release from the ewe hypothalamus
      in vitro: sensitivity to oestradiol.
AB  - The present study aims at ascertaining the influence of alpha(1)-adrenoreceptors
      on arginine vasopressin (AVP) release in vitro and determine whether E(2)
      modulates the alpha(1)-adrenoreceptor and AVP interaction. Ten minutes after ewe
      killing, sagittal midline hypothalamic slices (from the anterior preoptic area to
      the mediobasal hypothalamus with the median eminence, 2 mm thick, 2 per sheep)
      were dissected, placed in oxygenated minimum essential media-alpha (MEM-alpha) at
      4 degrees C and within 2 h were singly perifused at 37 degrees C with oxygenated
      MEM-alpha (pH 7.4; flow rate 0.15 ml/min), either with or without E(2) (24
      pg/ml). After 4 h equilibration, 10 min fractions were collected for 4 h
      interposed with 10 min exposure at 60 min to a specific alpha(1)-adrenoreceptor
      agonist or antagonist at various doses (0.1-10 mm). At the end of all
      perifusions, slices responded to KCl (100 mm) with AVP efflux (p < 0.05). Release
      of AVP was enhanced (p < 0.05) by the alpha(1)-adrenoreceptor agonist
      (methoxamine 10 mm; no E(2), n = 7 perifusion chambers: from 14.3 +/- 2.7 to 20.9
      +/- 3.9, with E(2), n = 10: from 10.7 +/- 1.2 to 18.4 +/- 3.4 pg/ml) or the
      antagonist (thymoxamine 10 mm; no E(2), n = 5: from 9.5 +/- 3.1 to 30.4 +/- 6.0,
      with E(2), n = 10: from 10.8 +/- 0.9 to 39.1 +/- 6.3 pg/ml). With the agonist,
      the response occurred only at 80 min (p < 0.05) both in the presence and absence
      of E(2). Whereas, after the antagonist, values were higher (p < 0.05) throughout
      the post-treatment period (80-170 min) without E(2), but declined by 150 min in
      the presence of E(2). Furthermore, the response to the alpha(1)-adrenoreceptor
      antagonist was greater (p < 0.05; 90-140 min) than the agonist only in the
      presence of E(2). In conclusion, these results reveal direct alpha(1)
      adrenoreceptor-mediated control of the hypothalamic AVP neuronal system which is
      modulated by E(2).

PMID- 18325002
TI  - Unusual vaginal angiomatous neoformation in a 3-year old pug.
AB  - A 3-year-old female pug (8 kg bodyweight) was referred by a local veterinarian
      for evaluation of vaginal bleeding. Historically, the owner indicated chronic
      haematic vaginal discharge initiated approximately 3 months ago, overall good
      appetite and slight general dullness. Two months prior to the visit, the bitch
      had been spayed by the local veterinarian, but vaginal bleeding persisted after
      surgery. Following a general examination and complete blood analysis, a genital
      tract examination was performed and, through vaginal endoscopy, a red, smooth,
      and apparently broad-based vaginal mass was found. An episiotomy was performed
      and on surgical exploration, the bleeding site was determined to be on the
      surface of a mass composed of two congested, adjacent cylindrical structures,
      symmetric to the vaginal sagittal midline, broad-based and quite regular on the
      surface. The mass appeared to be well delimited from the surrounding tissue by a
      thin capsula, and each cylindrical structure had a tributary vessel. Ectopic and
      dysplastic corpora cavernosa of the clitoris characterized by angiomatous
      proliferation, cavernous haemangioma and vascular hamartoma were considered in
      the differential diagnosis. The presence of small intralesional nerves identified
      by S100 immunostaining was used as a diagnostic clue to classify this unusual
      vaginal angiomatous neoformation as vascular hamartoma.

PMID- 18325003
TI  - Effects of hCG stimulation on hepatic activities of cytochromes P4502E1 and
      P4502A in pubertal male pigs.
AB  - The effects of human chorionic gonadotropin (hCG) stimulation on fat skatole
      concentrations and hepatic activities of cytochromes P4502E1 (CYP2E1) and P4502A
      (CYP2A) were studied in Landrace and Duroc breeds of entire male pigs. Pigs were
      divided into four groups: two control groups of each breed, without hCG
      stimulation (n = 20 for each breed), and two experimental groups of each breed,
      with hCG stimulation (n = 18 for each breed). Pigs were slaughtered 3 days after
      hCG stimulation and activities of CYP2E1 and CYP2A were measured in liver
      homogenate. Activities of both CYP2E1 and CYP2A were lower in hCG-stimulated pigs
      than control pigs for both Landrace (p = 0.005 for CYP2E1, p = 0.016 for CYP2A)
      and Duroc breeds (p = 0.003 for CYP2E1, p = 0.001 for CYP2A), and skatole
      concentrations in fat were higher in the hCG-stimulated pigs of both breeds (p <
      0.01). For both control and hCG-stimulated groups, Duroc pigs had lower skatole
      concentrations than Landrace pigs (p = 0.001 for both groups). The activity of
      CYP2E1 did not differ significantly between breeds in either the control group or
      the experimental group (p = 0.233 for control pigs and p = 0.210 for experimental
      pigs). However, whereas CYP2A activity did not differ significantly between
      breeds in the control groups (p = 0.181 for CYP2A), in the hCG-stimulated groups,
      CYP2A activity was lower in Duroc pigs than in Landrace (p = 0.011). Based on
      these findings, we conclude that hCG stimulation can suppress hepatic CYP2E1 and
      CYP2A activities, probably through an increase in the levels of testicular
      steroids. Between-breed variations in skatole levels in fat were not related to
      the activities of CYP2E1 and CYP2A.

PMID- 18325004
TI  - Effect of porcine and ovine FSH on nuclear maturation of pig oocytes in vitro.
AB  - The effect of porcine or ovine FSH on the maturation rate of porcine oocytes and
      on the time course of meiotic progression was studied. Groups of 20 grade-A
      cumulus oocyte complexes, aspirated from slaughterhouse cycling-gilt ovaries,
      were cultured in vitro in 400 mul of Modified Parker's Medium supplemented with
      oestrous cow serum and porcine FSH (Folltropin(R)-V, 0.50 mg/ml) or ovine FSH
      (Ovagen(TM), 0.44 iu/ml), in four-well dishes under mineral oil, at 38.5 degrees
      C, 5% CO(2) in humidified air. At the end of each 3-h interval, from 3 to 42 h of
      culture, the nuclear status of oocytes was assessed microscopically (1000x),
      after fixation (methanol/acetic acid: 3/1) and orcein (2%) staining. Oocytes were
      classified as (i) immature (IMM), i.e. oocytes at germinal vesicle stage,
      germinal vesicle break down and prophase I, (ii) metaphase I (MI) and (iii)
      metaphase II (MII), i.e. oocytes at anaphase I, telophase I and metaphase II.
      Data were analysed using regression analysis, chi-square and t-test. Nuclear
      status was assessed in 1610 oocytes (porcine FSH: 787, ovine FSH: 823). Most of
      the oocytes were at MI from 24 to 33 h (porcine FSH 60.27%, ovine FSH 42.80%, p <
      0.001) and at MII from 36 to 42 h (porcine FSH 80.38%, ovine FSH 67.45%, p <
      0.01) of culture. Significantly higher maturation rate was observed in porcine
      FSH than in ovine FSH treated oocytes (86.69 +/- 12.97%, 71.34 +/- 9.86%, mean +/
      SD, p < 0.05), after 42 h of culture. In conclusion, under the specific culture
      conditions, porcine FSH seems to support pig oocyte maturation better than ovine
      FSH.

PMID- 18325005
TI  - Effects of the reproductive status on morphological oocyte quality and
      developmental competence of oocytes after in vitro fertilization and somatic cell
      nuclear transfer in cat.
AB  - This study was conducted to examine the effects of the reproductive cycle of
      donor cat on the quality of oocytes at recovery and developmental competence of
      oocytes after in vitro fertilization (IVF) and somatic cell nuclear transfer
      (NT). Based on the presence or absence of follicles and corpora lutea, the
      ovarian pairs collected were classified into inactive, follicular or luteal
      stages. After collection of oocytes, the oocytes were classified into four grades
      according to the morphological condition of oocyte cytoplasm and cumulus cells. A
      total of 16 558 oocytes were obtained from 198 ovarian pairs. The total mean
      numbers of oocytes and the mean numbers of oocytes with high quality (grade I)
      were significantly higher in ovarian pairs at the inactive stage (111.1 and 19.0
      oocytes, respectively) than in ovarian pairs at the follicular stage (67.1 and
      11.4 oocytes, respectively). A significant difference in the proportions of
      oocytes with grade I out of the total examined oocytes was observed between the
      follicular and luteal stages of ovaries (14.9% vs 20.2%, p < 0.05). The
      proportions of IVF embryos cleaved and developed to blastocysts significantly
      decreased with decreased quality of oocytes at recovery, irrespective of the
      reproductive status of ovaries. Moreover, there were no significant differences
      in the proportions of cleavage and development to the blastocyst stage of IVF and
      NT embryos among three oestrous stages of ovaries. These results indicate that
      the reproductive cycle stage of donor cat ovaries has no apparent effects on the
      in vitro development of oocytes after IVF and NT, but the quality of oocytes at
      recovery influences the development of IVF embryos.

PMID- 18325006
TI  - Electrolytes changes in mammary secretions before foaling in jennies.
AB  - No knowledge regarding the peripartum changes in mammary secretions in the jenny
      are presently available in literature. In the mare, instead, several studies
      report the role of these changes as indicators of foetal readiness for birth and
      impending parturition. This experiment was designed to determine calcium, sodium,
      potassium concentrations, and the value of sodium/potassium ratio in mammary
      fluids during prepartum in the jenny. Samples were daily collected by hand
      milking, after mammary gland size increased noticeably, from 17 Martina Franca
      jennies. Prepartum mammary secretions were analysed every other day between day
      10 and day 2 antepartum, and then once a day from the day before to the day of
      parturition. Calcium concentration showed a significant increase between day 10
      and day 6 antepartum and then between day 6 and days 4 and 2. Afterwards, another
      statistical significant increase was observed at parturition. Sodium
      concentration significantly decreased from day 10 to day 2 prepartum. Potassium
      concentration significantly increased between day 10 and day 8 before
      parturition, then showed a further increase at day 4, followed by none
      significant changes until foaling. All jennies showed a reversal in
      sodium/potassium ratio between 2 days antepartum and the day before. In
      conclusion, the evaluation of mammary fluid calcium concentrations and the
      reversal of sodium/potassium ratio could be used as good indicators of foetal
      maturity in the jenny. As far as the prediction of parturition is concerned, the
      reversal of sodium/potassium ratio is the best parameter, since it was detected
      48-24 h before parturition in all considered animals.

PMID- 18325007
TI  - Body size and testicular traits of tropically-adapted bucks raised under
      extensive husbandry in Ethiopia.
AB  - Five tropically adapted buck breeds extensively managed in Ethiopia were studied
      to determine possible effects of breed and age on body size and testicular
      traits. In all, 177 bucks were selected following stratified random sampling, and
      evaluated in three age groups: <14 months (young), 14-19.5 months (intermediate)
      and 19.6-24 months (old). The breeds studied were Arsi-Bale (AB; N = 35), Central
      Highlands (CH; N = 33), Afar (N = 35), Boran (N = 36) and Woito-Guji (WG; N =
      38). In all the three age groups, Boran and CH bucks were the heaviest (p <
      0.05), Afar were the lightest, and AB and WG were in between. The highest body
      weight (BW) was achieved in the intermediate age group for Afar, but in the
      oldest age group for the other breeds. In the youngest age group, scrotal
      circumference (SC) was the widest (p < 0.05) for Boran and CH and the narrowest
      for Afar, AB and WG, while in the intermediate and the oldest age groups, Boran
      showed the widest SC. Boran, WG and CH had higher (p < 0.05) testicular weight
      (TW) than Afar and AB in the youngest age group. Boran retained the highest (p <
      0.05) TW in the intermediate and the oldest age groups, while in the oldest age
      group WG and AB medium TW and Afar had the lowest TW. However, Afar had the
      highest TW expressed as percentage of BW. SC was well correlated with TW (p <
      0.001; r = 0.74) and BW (p < 0.001; r = 0.61), indicating a linear, positive
      association between BW and TW (p < 0.001; r = 0.51). In conclusion, body size and
      testicular traits of Ethiopian bucks under an extensive management system are
      influenced differently by breed and age group.

PMID- 18325008
TI  - Embryo production in superovulated goats treated with insulin before or after
      mating or by continuous propylene glycol supplementation.
AB  - Seventeen adult and cyclic Moxoto goats were synchronized using 60 mg MPA vaginal
      sponge for 11 days and 50 mug cloprostenol, 48 h before sponge removal, and
      superovulated with 120 mg pFSH i.m. in decreasing doses at 12 h intervals for
      three consecutive days. In seven goats, 0.2 IU/kg BW/day of long acting insulin
      was subcutaneously injected at same time as pFSH, and in the other five goats,
      the same dose of insulin was injected for three consecutive days starting 24 h
      after mating. Finally, five goats were supplemented with an oral dose of 80
      ml/goat/day of propylene glycol continuously during the experiment. The animals
      were flushed at 7 days after mating and the embryos were classified based on
      International Embryo Transfer Society criteria. Blood samples were collected
      every 3 days for insulin assay. Administration of insulin raised the insulin
      levels of the goats (p < 0.05), whereas in the group treated with propylene
      glycol, insulin rate was different only between FSH treatment and after mating (p
      < 0.05). Similar rates of recovery for total (80.05 +/- 9.78%) or transferable
      structures (61.03 +/- 15.13%) were obtained. Treatment was not influenced (p >
      0.05) by responsiveness to superovulation, which averaged 64%. By contrast,
      insulin treatments were shown to increase the number of embryos considered
      excellent with respect to goats supplemented with propylene glycol (p < 0.05).
      When insulin was given before mating, a strong relationship (r = 0. 90) (p <
      0.05) between number of transferable embryo and ovulations was observed in the
      animals. In conclusion, superovulated goats treated with low doses of exogenous
      insulin resulted in an enhancement in embryo quality, which was related to
      changes in circulating insulin concentrations.

PMID- 18325010
TI  - Abstracts of the 22nd European Immunogenetics and Histocompatibility Conference.
      Toulouse, France. April 2-5, 2008.

PMID- 18325011
TI  - Is streamlined evaluation of children for epilepsy surgery possible?
AB  - BACKGROUND: The presurgical evaluation of children with intractable epilepsy
      includes evaluation by an experienced clinician, MRI, video EEG, and functional
      imaging techniques to localize seizure onset. However, the contributions of each
      investigation to surgical decision making has not been systematically assessed.
      METHOD: Data used for decision on eligibility for surgery on 353 children was
      discussed at a presurgical multidisciplinary meeting and systematically recorded.
      The relationships between MRI, EEG, SPECT findings, and the probability of being
      offered epilepsy surgery were investigated retrospectively using a quick unbiased
      statistical tree (QUEST). RESULTS: Sixteen children were offered nonresective
      surgery. Of the remaining, 236 (70%) were offered resective surgery. The
      proportion of children with a localized lesion on MRI offered resective surgery
      was 92%[95% CI: 88 to 95%], and EEG telemetry did not modify decision making in
      this group (p < 0.001). In children with bilateral MRI changes or normal scan the
      probability of being offered resective surgery was 78% in those with localized
      ictal onset on EEG compared to 9% with nonlocalized EEG (p < 0.001). SPECT did
      not appear to systematically influence decision making in any group. CONCLUSION:
      Children with medically intractable epilepsy and localized lesions on MRI may not
      necessarily need ictal EEG recordings or SPECT prior to offering resective
      surgery. More targeted use of EEG telemetry could allow more children with less
      obvious surgical targets to be investigated without increasing resources.

PMID- 18325012
TI  - Seizures following picornavirus infection.
AB  - PURPOSE: We demonstrate the establishment and characterization of a novel virus
      infection-induced seizure model in C57BL/6 mice. METHODS: C57BL/6 mice were
      infected with Theiler's murine encephalomyelitis virus (TMEV) or mock infected.
      Mice were followed for seizures, weight change, body temperature, motor function
      (righting reflex, rotorod) and neurological manifestations (inflammation
      [perivascular cuffing], pyknotic neurons, transforming growth factor [TGF]-beta
      expression). RESULTS: C57BL/6 mice are susceptible to seizures induced by TMEV
      infection. Approximately 50% of C57BL/6 mice develop transient afebrile seizures.
      Motor function and coordination are impaired in seized mice. Pyramidal neuron
      pyknosis and TGF-beta expression correlate with seizure activity in the
      hippocampus. DISCUSSION: The characterization of this model will enable the
      investigation of viral and immune contributions in the central nervous system to
      the development of seizure disorders in humans.

PMID- 18325013
TI  - Clinical picture of EPM1-Unverricht-Lundborg disease.
AB  - Unverricht-Lundborg disease (ULD), progressive myoclonic epilepsy type 1 (EPM1,
      OMIM254800), is an autosomal recessively inherited neurodegenerative disorder
      characterized by age of onset from 6 to 16 years, stimulus-sensitive myoclonus,
      and tonic-clonic epileptic seizures. Some years after the onset ataxia,
      incoordination, intentional tremor, and dysarthria develop. Individuals with EPM1
      are mentally alert but show emotional lability, depression, and mild decline in
      intellectual performance over time. The diagnosis of EPM1 can be confirmed by
      identifying disease-causing mutations in a cysteine protease inhibitor cystatin B
      (CSTB) gene. Symptomatic pharmacologic and rehabilitative management, including
      psychosocial support, are the mainstay of EPM1 patients' care. Valproic acid, the
      first drug of choice, diminishes myoclonus and the frequency of generalized
      seizures. Clonazepam and high-dose piracetam are used to treat myoclonus, whereas
      levetiracetam seems to be effective for both myoclonus and generalized seizures.
      There are a number of agents that aggravate clinical course of EPM1 such as
      phenytoin aggravating the associated neurologic symptoms or even accelerating
      cerebellar degeneration. Sodium channel blockers (carbamazepine, oxcarbazepine)
      and GABAergic drugs (tiagabine, vigabatrin) as well as gabapentin and pregabalin
      may aggravate myoclonus and myoclonic seizures. EPM1 patients need lifelong
      clinical follow-up, including evaluation of the drug-treatment and comprehensive
      rehabilitation.

PMID- 18325014
TI  - Autonomic consequences of kainic acid-induced limbic cortical seizures in rats:
      peripheral autonomic nerve activity, acute cardiovascular changes, and death.
AB  - PURPOSE: Autonomic consequences of seizures are common, but can be severe. We
      sought to define changes in autonomic activity from limbic cortical seizures and
      their impact on the heart. METHODS: We studied kainic acid (KA)-induced seizures
      in urethane-anesthetized rats using peripheral nerve, blood pressure (BP), and
      ECG recordings and echocardiography. RESULTS: Seizures were associated with
      massive increases in parasympathetic (vagus nerves) and sympathetic (cervical
      sympathetic ganglion >renal nerve >splanchnic nerve) activity. Seizure-associated
      activity increases were greater than activity changes induced by nitroprusside or
      phenylephrine (each producing BP changes of >50 mmHg). Increases in c-fos
      expression were found in both sympathetic and parasympathetic medullary regions
      (as well as hypothalamic areas). Baroreceptor reflex function (tested with
      nitroprusside and phenylephrine) was impaired during seizures. Finally, a
      significant fraction of the animals died and the mechanism of death was defined
      through ECG, BP, and echocardiographic measures to be profound cardiac dilatation
      and bradyarrhythmia leading to hypoperfusion of the brain and ultimately
      hypoperfusion of the heart. Cardiovascular changes occur within seconds (or less)
      of autonomic nerve activity changes and death by these mechanisms takes minutes.
      DISCUSSION: We propose that the massive parasympathetic and sympathetic outflow
      that occurs during a seizure gets compounded by respiratory distress (driving
      both autonomic nervous system divisions in the same direction) causing mechanical
      dysfunction, slowing the heart, and hypoperfusing the brain.

PMID- 18325015
TI  - Prenatal freeze lesioning produces epileptogenic focal cortical dysplasia.
AB  - PURPOSE: Focal cortical dysplasia (FCD) is thought to be an important cause of
      intractable epilepsy. However, its epileptogenicity remains unclear. Therefore,
      we created a novel rat model by freeze lesioning during the late embryonic stage
      to verify whether FCD influences seizure activities. METHODS: At 18 days
      postconception, a frozen probe was placed on the left scalp of a Sprague-Dawley
      rat embryo through the uterus wall. For 40 consecutive days from postnatal day 38
      (P38), electrical kindling stimulation was applied to the frontal lobes of male
      rat pups. Afterdischarges (ADs) were measured in both the cortex and hippocampus.
      Brain tissues were examined by immunohistochemistry. RESULTS: All brains from
      prenatally freeze-lesioned rats displayed severe disorganization of the cortical
      layers with randomly oriented dendrites/axons. In addition, heterotopic cortices
      were observed in 42.1% of cases. ADs in the cortex and hippocampus were
      significantly prolonged in freeze-lesioned rats compared with those in sham
      operated and control rats. FCD rats also revealed early development of
      hippocampal kindling and spontaneous cortico-hippocampal spikes, even in the
      chronic EEG recordings. Immunoreactivities for N-methyl-D-aspartate receptor
      (NMDAR) subunit 2B and glutamate/aspartate transporter in the lesions were
      significantly enhanced compared with the nonlesioned side, even in the absence of
      electrical stimulation. After electrical stimulation, NMDAR1 and 2B were markedly
      upregulated not only in the FCD, but also in the hippocampus. CONCLUSIONS:
      Prenatal freeze lesioning of the brain produces a severe neuronal migration
      disorder, closely mimicking human FCD. Our model suggests that FCD is associated
      with vulnerability to epilepsy, and may augment hippocampal epileptogenicity.

PMID- 18325016
TI  - Pronounced increase in breathing rate in the "hair dryer model" of experimental
      febrile seizures.
AB  - In a study using a heated chamber for induction of experimental febrile seizures
      (eFS) in rat pups, ictal activity was shown to be precipitated by a respiratory
      alkalosis (Schuchmann et al., 2006). In sharp contrast to this, in a recent
      review Dube et al., (2007) suggest that the respiratory alkalosis is model
      specific, and that no increase in respiratory rate is observed in the widely used
      "hair dryer model" of eFS. The data in the present work, based on well
      established techniques for measuring respiratory rates in rat pups, show a
      pronounced increase in the "hair dryer model" with values that are slightly
      higher than those recorded in the heated chamber model. Hence, a temperature
      evoked increase in respiration is a common feature of these two models of eFS.

PMID- 18325017
TI  - Status epilepticus: clinical presentation, cause, outcome, and predictors of
      death in 119 Ethiopian patients.
AB  - PURPOSE: Status epilepticus (SE) is a common neurological emergency with high
      morbidity and mortality. There is no study that has been conducted among
      Ethiopian patients with SE. The purpose of this study was to analyze clinical
      presentation, causes, complications, outcomes, and predictors of mortality.
      METHODS: In this retrospective study, patients aged >or=13 year with SE were
      included. Medical records were reviewed and demographic and clinical data were
      collected. RESULTS: Records of 119 patients were analyzed; preexisting epilepsy
      was found in 38.7%. Primarily generalized and focal with secondarily generalized
      (FWSG) seizures were identified in 60.5% and 36%, respectively. Simple partial SE
      occurred in 3.4%. Central nervous system (CNS) infection was the most common
      cause of SE in the whole group as well as in those with new onset seizure.
      Antiepileptic drug withdrawal (AEDW) was the main cause in those with preexisting
      seizure. One or more complications were detected in 61%. Intravenous diazepam and
      oral phenytoin were given to 95% and 97.5%, respectively. Case fatality was
      20.2%; poor outcome occurred in 24%. Predictors of mortality were FWSG type,
      acute symptomatic etiology, stroke, systemic infection, and HIV/AIDS and its CNS
      complications. Idiopathic and SE due to AEDW were associated with good prognosis.
      CONCLUSIONS: CNS infection was the most common cause of SE in the whole group and
      AEDW was the major cause in patients with preexisting epilepsy. Parenteral
      anticonvulsants, emergency measurement of serum AED level, and
      electroencephalography for urgent diagnosis and monitoring were unavailable.
      Mortality was related to underlying etiologies especially HIV/AIDS and its CNS
      complications.

PMID- 18325018
TI  - Reduced serum level of THDOC, an anticonvulsant steroid, in women with
      perimenstrual catamenial epilepsy.
AB  - PURPOSE: Seizure exacerbation in catamenial epilepsy (CE) is associated with the
      decrease in progesterone secretion and increase in estradiol secretion during the
      premenstrual period. Moreover, experimental evidence suggests that
      tetrahydrodeoxycorticosterone (THDOC), a positive modulator of the type A
      receptor for gamma-aminobutyric acid (GABA), and dehydroepiandrosterone sulfate
      (DHEAS), a negative modulator of this receptor, might play a crucial role in
      modulating seizure frequency during the menstrual cycle. Following these studies
      it seems of interest to investigate possible variations, among other hormonal
      parameters, of THDOC and DHEAS in CE patients. METHODS: The serum concentrations
      of progesterone (P4), pregnenolone, allopregnanolone (AP), THDOC, DHEAS,
      cortisol, and DHEAS/cortisol ratio were measured throughout the menstrual cycle
      at the 7th, 11th, 15th, 19th, 23rd, and 27th day from the onset of spontaneous
      menstrual blood loss in young premenopausal women with CE (n = 17) and age
      matched controls (n = 13). RESULTS: At each time of the study, the serum
      concentration of THDOC and the DHEAS/cortisol ratio were lower (p < 0.05) in
      women with CE than in control women. The concentrations of P4, pregnenolone, and
      AP did not differ between the two groups of subjects. CONCLUSIONS: The reduced
      serum concentration of THDOC and the reduced DHEAS/cortisol ratio detected
      throughout the menstrual cycle in women with CE might play a role in CE.
      Moreover, the peculiar pattern of CE seizure exacerbation might suggest that
      these neuroendocrine variations are worth investigating in other epileptic
      syndromes, particularly in those characterized by relevant and uncontrolled
      variations in seizure frequency.

PMID- 18325019
TI  - The diagnostic value of oral lacerations and incontinence during convulsive
      "seizures".
AB  - PURPOSE: Oral lacerations and urinary incontinence have long been considered
      useful clinical features for the diagnosis of epileptic seizures; however, both
      are also reported in patients with psychogenic nonepileptic seizures (PNES). The
      aims of the study were (1) to investigate whether the presence and nature of oral
      lacerations or incontinence during convulsive seizures of patients with epilepsy
      differed from those with PNES, and (2) whether the side of the oral laceration
      has any correlation with the epilepsy syndrome or lateralization. METHODS: Eighty
      four consecutive patients who experienced at least one convulsive event during
      video-EEG monitoring (VEM) were questioned and examined for oral lacerations and
      incontinence. Seizure classification was determined by a team of epileptologists
      based on the VEM findings and other clinical and investigational data, blinded to
      the oral laceration and incontinence information. RESULTS: The presence of oral
      lacerations among patients with epileptic seizures was 26% (17/66), in contrast
      it was 0% (0/18) with PNES (p = 0.01). Of the oral lacerations sustained by
      patients during an epileptic seizure, 14 were to the side of the tongue, one to
      the tip of the tongue, two to the cheek, and three to the lip. No significant
      relationships were observed between seizure lateralization and oral lacerations.
      Incontinence occurred in 23% (15/66) of epilepsy patients and 6% (1/18) of PNES
      patients (p = 0.09). There was no relationship between epilepsy type or
      lateralization and the prevalence of incontinence. CONCLUSIONS: Despite frequent
      reports of oral lacerations and incontinence by patients with PNES, objective
      evidence for this is highly specific to convulsive epileptic seizures.

PMID- 18325020
TI  - The anticonvulsant profile of rufinamide (CGP 33101) in rodent seizure models.
AB  - PURPOSE: To evaluate the anticonvulsant profile and behavioral toxicity of
      rufinamide in animal seizure models compared to the established antiepileptic
      drugs (AEDs): phenytoin, phenobarbital, valproate, and ethosuximide, or vehicle.
      METHODS: In acute studies of anticonvulsant efficacy, the AEDs were administered
      via oral (CF1 mice and Sprague-Dawley rats) and intraperitoneal (CF1 mice)
      routes. The AEDs were assessed for their ability to inhibit seizures induced by
      maximal electroshock (MES) or subcutaneous pentylenetetrazol, and ability to
      block seizures induced by subcutaneous strychnine, bicuculline, or picrotoxin.
      Tolerance of oral rufinamide was assessed in rats following 5-day (versus single
      dose) treatment with oral rufinamide using the dose equivalent necessary to
      achieve a 50% decrease in seizure frequency (ED(50)). Metabolic tolerance was
      also evaluated using an in vitro liver microsomal assay. RESULTS: Oral rufinamide
      suppressed pentylenetetrazol-induced seizures in mice (ED(50) 45.8 mg/kg) but not
      rats, and was active against MES-induced tonic seizures in mice (ED(50) 23.9
      mg/kg) and rats (ED(50) 6.1 mg/kg). Intraperitoneal rufinamide suppressed
      pentylenetetrazol-, bicuculline-, and picrotoxin-induced clonus in mice (ED(50)
      54.0, 50.5, and 76.3 mg/kg, respectively). Rufinamide was partially effective in
      the mouse strychnine test. The behavioral toxicity of rufinamide was similar to
      or better than established AEDs tested in this study. In general, the protective
      index of rufinamide was greater than that of the other AEDs. CONCLUSIONS: The
      efficacy and behavioral toxicity profiles in these animal models suggest that
      rufinamide may be effective in the treatment of generalized and partial seizures.

PMID- 18325021
TI  - The relationship between restless legs syndrome and cardiovascular disease.

PMID- 18325022
TI  - Comparison of botulinum toxin injection and neurotomy in patients with distal
      lower limb spasticity.
AB  - BACKGROUND AND PURPOSE: We compared the efficacy of botulinum toxin injection
      (BTI) and tibial nerve neurotomy (TNN) in an open-label study of 34 post-stroke
      hemiplegic patients with distal lower limb deformation. METHODS: The dose of BT
      was 300 U (Botox). TNN was performed with a 6-12 month delay on the motor
      branches of the tibial nerve. Muscles to be treated were selected according to
      the distal deformity (equinus, varus and clawing toes). Patients were assessed
      following each treatment for spasticity, motor control, range of movements,
      balance, gait and the Rivermead Motor Assessment. RESULTS: TNN (M3, M6 and Y1)
      resulted in a more significant effect than BTI (D15, M2 and M5) on most of the
      measures: ankle plantar flexor spasticity, range of movement in dorsiflexion and
      eversion, foot position in upright situation, Functional Ambulation Categories
      (barefoot), RMA, gait velocity (comfortable condition), subjective benefit and
      use of walking aids. Patients treated for tibialis posterior or flexor digitorum
      longus spasticity often complained of subjective sensory disorders at the plantar
      sole over a period of 4-6 weeks. CONCLUSION: In conclusion, TNN is more effective
      than BTI on most of the functional parameters. The interest of BTI lies in the
      preliminary testing of the efficacy of a technique for reducing spasticity on
      lower limb function.

PMID- 18325023
TI  - ALS patients request more information about cognitive symptoms.
AB  - BACKGROUND AND PURPOSE: Once thought to impact only voluntary motor function,
      ALS/Motor neuron disease (MND) is now seen as a multi-system disorder in which a
      minority of patients experience mild cognitive dysfunction or frontotemporal
      dementia. Despite clinical guidelines advocating supplying complete information
      to patients, educational materials on ALS often state that the mind is
      unaffected. We sought to establish how much patients and caregivers understand
      about ALS, what they have been told to expect by their physician, and if they
      would have appreciated more complete information. METHODS: A two-part survey was
      administered online. An 'ALS quiz' gauged participants' knowledge of physical and
      psychological aspects of ALS. A second questionnaire assessed which symptoms
      patients had discussed with their clinician and explored patients' desire to
      receive information on psychological effects. RESULTS: A total of 247 ALS
      patients and 87 caregivers participated. Participants knew less about
      psychological symptoms than physical ones (72% correct responses versus 82%;
      paired t((333)) = -5.04, P < 0.001). Patients commonly reported being told by
      their doctor about physical symptoms such as problems walking (85%) or
      stiffness/cramps (74%) but not psychological issues like emotional lability (46%)
      or cognitive change (11%). The majority of patients (62%) and carers (71%)
      indicated a desire to be informed that cognitive change or dementia might occur.
      CONCLUSION: ALS is a multi-system disorder. However, despite a desire for more
      information from patients and their carers, healthcare professionals continue to
      primarily address only the physical consequences of the disease.

PMID- 18325024
TI  - Impact of fatigue on quality of life in patients with Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Fatigue is frequent and important in the lives of
      Parkinson's disease (PD) patients. It is multidimensional, with physical and
      mental aspects. The aim of our study was to explore the impact of fatigue on
      quality of life (QoL) for PD patients. METHODS: The sample consisted of 175 PD
      patients from Eastern Slovakia (52% males, mean age 68.2 +/- 9.2, mean disease
      duration 7.4 +/- 6.7). The Multidimensional Fatigue Inventory (five dimensions),
      the Parkinson's Disease Quality of Life Questionnaire (eight dimensions) and the
      Unified Parkinson's Disease Rating Scale were used. Demographic data were
      obtained in a structured interview. Fisher's exact test, t-test, and multiple
      linear regression analysis were used. RESULTS: Different aspects of fatigue
      selectively explained different domains of QoL - physical dimensions of fatigue
      were connected with Mobility and Activities of daily living; mental fatigue
      dimensions affected Cognition, Emotional well-being, Communication and Activities
      of daily living; general fatigue was related to Bodily discomfort. The explained
      variances varied from 5% (Social support) to 65% (Activities of daily living).
      CONCLUSION: Fatigue combined with worse functional status appears to be a
      significant contributor to poor quality of life. Its multidimensional construct
      can be used to develop strategies for improving specific aspects of fatigue to
      improve QoL for PD patients.

PMID- 18325025
TI  - Cytidine-5'-diphosphocholine (Citicoline): a pilot study in patients with non
      arteritic ischaemic optic neuropathy.
AB  - BACKGROUND AND PURPOSE: Our work evaluates visual function before and after
      treatment with cytidine-5-diphosphocholine (Citicoline) in patients with non
      arteritic ischaemic optic neuropathy (NION). METHODS: Twenty-six patients in
      which at least 6 months elapsed from NION, were randomly divided into two age
      similar groups: 14 patients had Citicoline (Cebrolux-Tubilux, Italy, 1600 mg/diem
      for 60 days, followed by a 120-day period of wash out, days 60-180) (T-NION); 12
      patients had no treatment during the same period (NT-NION). At day 180, in T-NION
      a second period of treatment (days 181-240) followed by a wash-out (days 241-360)
      was performed. Fourteen age-matched healthy subjects provided normative data. In
      all patients, pattern-electroretinogram (PERG), visual evoked potentials (VEPs)
      and visual acuity (VA) measurements were performed at baseline and at days 60 and
      180. In T-NION, further measurements were achieved at days 240 and 360. RESULTS:
      At baseline, NT-NION and T-NION patients showed abnormal PERGs and VEPs, and
      reduced VA, compared to controls. At the end of treatment (days 60 and 240), T
      NION patients showed improvement (P < 0.01) of PERGs, VEPs parameters and VA,
      compared to pre-treatment values. After wash out, functional improvements
      persisted compared to baseline. No changes in NT-NION patients were observed.
      CONCLUSIONS: Our results suggest a beneficial effect of oral Citicoline in NION.

PMID- 18325026
TI  - Exacerbation of chronic pancreatitis induced by anticholinesterase medications in
      myasthenia gravis.

PMID- 18325027
TI  - Risk factors and outcome of seizures after spontaneous aneurysmal subarachnoid
      hemorrhage.
AB  - BACKGROUND AND PURPOSE: Seizures are important neurologic complications of
      spontaneous aneurysmal subarachnoid hemorrhage (SAH). A better understanding of
      the risk factors of seizures following aneurysmal SAH is needed to predict those
      who will require treatment. METHODS: A total of 137 adult patients were enrolled
      in this two-year retrospective study. Baseline prognostic variables were analyzed
      based on Cox's proportional hazards model after a minimum of one-year follow-up.
      RESULTS: Seizures occurred in 21 patients who had SAH, including acute
      symptomatic seizures in 11.7% (16/137) and unprovoked seizures in 3.6% (5/137).
      None progressed to status epilepticus during hospitalization. After a minimum of
      one-year follow-up, the mean Glasgow Outcome Score was 3.5 +/- 1.4 for patients
      with seizures and 3.1 +/- 1.1 for those without. CONCLUSIONS: Higher mean World
      Federation of Neurological Societies grade on presentation was predictive of
      seizure, but seizure itself was not a significant prognostic predictor after a
      minimum of one-year follow-up. Regarding potential side effects of anti-epileptic
      drugs, anti-epileptic therapy should be carefully administered to patients with
      seizures after aneurysmal SAH.

PMID- 18325028
TI  - Concomitant diagnosis of sarcoidosis and incontinentia pigmenti in an epileptic
      patient.

PMID- 18325029
TI  - Growth, activity and temperature responses of ammonia-oxidizing archaea and
      bacteria in soil microcosms.
AB  - Ammonia oxidation, as the first step in the nitrification process, plays a
      central role in the global cycling of nitrogen. Although bacteria are
      traditionally considered to be responsible for ammonia oxidation, a role for
      archaea has been suggested by data from metagenomic studies and by the isolation
      of a marine, autotrophic, ammonia-oxidizing, non-thermophilic crenarchaeon.
      Evidence for ammonia oxidation by non-thermophilic crenarchaea in marine and
      terrestrial environments is largely based on abundance of bacterial and archaeal
      ammonia monooxygenase (amo) genes, rather than activity. In this study, we have
      determined the influence of temperature on the response of ammonia-oxidizing
      bacteria and archaea in nitrifying soil microcosms using two approaches,
      involving analysis of transcriptional activity of 16S rRNA genes and of a key
      functional gene, amoA, which encodes ammonia monooxygenase subunit A. There was
      little evidence of changes in relative abundance or transcriptional activity of
      ammonia-oxidizing bacteria during nitrification. In contrast, denaturing gradient
      gel electrophoresis analysis of crenarchaeal 16S rRNA and crenarchaeal amoA genes
      provided strong evidence of changes in community structure of active archaeal
      ammonia oxidizers. Community structure changes were similar during incubation at
      different temperatures and much of the activity was due to a group of non
      thermophilic crenarchaea associated with subsurface and marine environments,
      rather than soil. The findings suggest a role for crenarchaea in soil
      nitrification and that further information is required on their biogeography.

PMID- 18325030
TI  - Separating the left cardiac ventricle from the atrium in short axis MR images
      using the equation of the atrioventricular plane.
AB  - Short axis (SA) images obtained from cardiac magnetic resonance imaging are used
      to advantage in the calculation of important clinical parameters such as the
      ejection fraction and stroke volume (SV). A prerequisite for these calculations
      is the separation of the left ventricle and the left atrium. When only using the
      information seen in the SA images this separation can be a source of error due to
      the through-plane motion of the basal part of the left ventricle. In this study a
      method is proposed where the separation of the left ventricle and the atrium is
      performed by identifying the intersections of the atrioventricular plane in the
      SA images. The equation of the atrioventricular plane was determined in both
      systole and diastole using long axis and four chamber image views. Stroke volumes
      were measured in 20 patients using SA images where the endocardium had been
      delineated. The SV obtained using the new method was compared with quantitative
      flow measurements and the conventional technique for calculation of SV from SA
      images, respectively. The agreement of SV was, according to Bland-Altman
      analysis, 2.0 ml (95% CI -12.0 to 15.9 ml) in comparison with the flow
      measurements and 2.2 ml (95% CI -9.2 to 13.6 ml) compared to the conventional
      method. Inter- and intra-observer variability, when using the new proposed
      method, was small. This study shows that the identification of the left
      atrioventricular plane in SA images can be used in the separation of the left
      atrium and ventricle.

PMID- 18325031
TI  - Montelukast inhibits tumour necrosis factor-alpha-mediated interleukin-8
      expression through inhibition of nuclear factor-kappaB p65-associated histone
      acetyltransferase activity.
AB  - BACKGROUND: Montelukast is a potent cysteinyl leukotriene-1 receptor antagonist
      possessing some anti-inflammatory effects although the molecular mechanism of
      these anti-inflammatory effects is unknown. In this study, we aimed to
      investigate the effect of montelukast on nuclear factor (NF)-kappaB-associated
      histone acetylation activity in phorbol myristate acetate (PMA)-differentiated
      U937 cells. METHODS: We examined the inhibitory effects of montelukast on TNF
      alpha-induced IL-8 production in PMA-differentiated U-937 cells. U-937 cells were
      exposed to PMA (50 ng/mL) for 48 h to allow differentiation to macrophages.
      Macrophages were then exposed to TNF-alpha (10 ng/mL) in the presence or absence
      of montelukast (0.01-10 microm) for 24 h. After this time, the concentration of
      IL-8 in the culture supernatant was measured by sandwich-type ELISA kit. The
      effect of signalling pathways on TNF-alpha-induced IL-8 release was examined
      pharmacologically using selective NF-kappaB/IKK2 (AS602868, 3 microm), (PD98059,
      10 microm) and p38 mitogen activated protein kinase (MAPK) (SB203580, 1 microm)
      inhibitors. NF-kappaB DNA binding activity was measured by a DNA-binding ELISA
      based assay. NF-kappaB-p65-associated histone acetyltransferase (HAT) activity
      was measured by immunoprecipitation linked to commercial fluorescent HAT.
      RESULTS: TNF-alpha-induced IL-8 release was suppressed by an NF-kappaB inhibitor
      but not by MEK or p38 MAPK inhibitors. Montelukast induced a concentration
      dependent inhibition of TNF-alpha-induced IL-8 release and mRNA expression that
      reached a plateau at 0.1 microm without affecting cell viability. Montelukast did
      not affect NF-kappaB p65 activation as measured by DNA binding but suppressed NF
      kappaB p65-associated HAT activity. CONCLUSION: Montelukast inhibits TNF-alpha
      stimulated IL-8 expression through changes in NF-kappaB p65-associated HAT
      activity. Drugs targeting these enzymes may enhance the anti-inflammatory actions
      of montelukast.

PMID- 18325032
TI  - Lack of eosinophilia can predict remission in wheezy infants?
AB  - BACKGROUND: Early wheezing in infants is a potential risk factor for persistence
      of asthma into adulthood. Moreover, a personal or familial history of atopy are
      risk factors associated with persistence of pre-existing wheezing during
      childhood. However, their relative importance remains unclear. OBJECTIVES:
      Firstly to determine the critical thresholds of common biological markers of
      atopy in wheezy infants associated with persistence of wheezing into childhood
      and secondly to rank these biological markers together with clinical parameters
      according to the strength of their association with wheezing persistence.
      METHODS: A cohort of infants less than 30 months old with recurrent wheezing was
      established in order to assess severity of respiratory symptoms and to look for
      the presence of atopy. At the age of 6 years, they were re-evaluated regarding
      remission of wheezing over the previous 12-months period. RESULTS: Data were
      available for 219 subjects. In 27% of them, wheezing persisted at 6 years of age.
      Critical biological thresholds associated with the risk of wheezing persistence
      were: (1) a blood eosinophilia count >or=470/mm(3) (defining eosinophilia), and
      (2) a total serum IgE level >or=45 IU/mL (defining elevated IgE) during infancy.
      A multiple component factorial analysis identified a dimension associating
      eosinophilia, elevated IgE and allergic sensitization on the one hand with
      persistent wheezing at 6 years of age on the other (lambda=0.15). According to a
      segmentation analysis, the main discriminative parameter of wheezing persistence
      was eosinophilia. Thus a lack of eosinophilia alone could account for 91% of
      infants in remission, and when combined with absence of allergic sensitization,
      remission was correctly discriminated in 96.9% of the study population.
      CONCLUSION: Our data strongly suggest that the lack of eosinophilia in wheezy
      infants without ongoing infection could predict future remission of wheezing in a
      large majority of cases.

PMID- 18325033
TI  - Novel approaches to the inhibition of mast cells in allergic disease.

PMID- 18325034
TI  - MRSA in livestock animals-an epidemic waiting to happen?
AB  - Screening of pig farmers and pigs in The Netherlands has revealed that >20% of
      pig farmers and 39% of slaughterhouse pigs are positive for an unusual strain of
      methicillin-resistant Staphylococcus aureus (MRSA) belonging to sequence type
      (ST) 398. It is now clear that the emergence of ST398 is not just a Dutch
      problem, with human infections being described in several European countries,
      Canada and Singapore. Furthermore, some human isolates have now acquired the
      genes encoding Panton-Valentine leukocidin. Livestock may become an important
      source of community-acquired MRSA. A concerted effort on the part of clinicians,
      infection control practitioners and veterinarians will be required to prevent
      further spread of this novel strain of MRSA.

PMID- 18325035
TI  - Reflections on the immunogenicity of therapeutic proteins.
AB  - Therapeutic proteins are now established as a major class of medication with
      proven efficacy in treating a wide range of diseases. The administration of such
      proteins to patients can lead to the development of antibodies that are able to
      bind and eventually neutralise the protein administered. Many advances have been
      made in understanding the immunogenicity of therapeutic proteins, but opinions
      are often conflicting. Although it is important to understand more about the
      antibodies generated against therapeutic proteins, the need for future research
      must not be neglected, so that other relevant factors can be identified and
      addressed to maximise treatment benefits for patients.

PMID- 18325036
TI  - Identification of Bordetella spp. in respiratory specimens from individuals with
      cystic fibrosis.
AB  - Bordetella spp. are not normally included when considering the opportunistic
      bacterial species that are typically involved in respiratory tract infections in
      individuals with cystic fibrosis (CF). By using a combination of bacterial
      genotyping and 16S rDNA sequencing, Bordetella spp. were identified in cultures
      obtained from 43 individuals with CF. Most (n = 23) patients were infected with
      Bordetella bronchiseptica/parapertussis; five were infected with Bordetella
      hinzii, four with Bordetella petrii, three with Bordetella avium, and eight with
      unidentified Bordetella spp. Consideration should be given to the presence of
      these organisms in the evaluation of CF sputum cultures.

PMID- 18325037
TI  - Secular changes in incidence and mortality associated with Staphylococcus aureus
      bacteraemia in Quebec, Canada, 1991-2005.
AB  - In order to examine secular changes in the incidence and mortality associated
      with Staphylococcus aureus bacteraemia before and after the emergence of
      methicillin-resistant S. aureus (MRSA), a retrospective cohort study of 815
      patients with S. aureus bacteraemia was performed in the Estrie region of Quebec,
      Canada, between 1991 and 2005. The primary outcome was all-cause 30-day
      mortality. Between 1991-1993 and 2003-2005, the proportion of cases attributed to
      endocarditis and pneumonia increased from 4% to 11% and from 2% to 11%,
      respectively, while that attributed to catheter infections decreased from 49% to
      17%. MRSA was almost absent in 1991-1999, but accounted for 10% and 20% of cases
      in 2000-2002 and 2003-2005, respectively. The population incidence of bacteraemia
      caused by methicillin-susceptible S. aureus (MSSA) remained stable between 1997
      and 2005, while that of MRSA increased from 0 to 7.4/100 000. Risk-factors for
      mortality included age, co-morbidities, female gender, residence outside the city
      of Sherbrooke, pneumonia (OR 3.35, 95% CI 1.96-5.73) or endocarditis (OR 2.89,
      95% CI 1.67-5.01) as the source, and an absence of treatment. After adjusting for
      confounders, patients with MRSA bacteraemia had a higher mortality rate than
      those with MSSA bacteraemia (OR 2.21, 95% CI 0.99-4.96, p 0.053). Mortality in
      patients with MSSA bacteraemia was 19% (16/83) in 1991-1993, 23% (26/113) in 1994
      1996, 29% (50/173) in 1997-1999, and 28% (52/185) in 2000-2002, decreasing to 15%
      (28/192) in 2003-2005, which impacted on the relative mortality rates of MRSA and
      MSSA. MRSA did not replace, but added to, an existing stable incidence of MSSA
      bacteraemia.

PMID- 18325038
TI  - Molecular characterisation of extended-spectrum beta-lactamase-producing
      Escherichia coli and Klebsiella spp. isolates at a tertiary-care centre in
      Lebanon.
AB  - The prevalence of bla CTX-M, bla TEM and bla SHV genes among extended-spectrum
      beta-lactamase (ESBL)-producing clinical isolates of Escherichia coli (n = 50)
      and Klebsiella spp. (n = 50) from Lebanon was 96%, 57% and 67%, and 40%, 82% and
      84%, respectively. Genotyping revealed that the clonal diversity was unrelated to
      the presence of bla genes. Sequence analysis of 16 selected isolates identified
      the bla CTX-M-15, bla TEM-1, bla OXA-1 and six bla SHV genes, as well as the gene
      encoding the quinolone-modifying enzyme AAC(6')-Ib-cr. The genes encoding CTX-M
      15 and AAC(6')-Ib-cr were carried on a 90-kb plasmid of the pC15-1a or pCTX-15
      type, which transferred both ESBL production and quinolone resistance from donors
      to transconjugants.

PMID- 18325039
TI  - Prevalence, characterisation and clinical profiles of Shiga toxin-producing
      Escherichia coli in The Netherlands.
AB  - Detection of Shiga toxin-producing Escherichia coli (STEC) in The Netherlands is
      traditionally limited to serogroup O157. To assess the relative importance of
      STEC, including non-O157 serogroups, stool samples submitted nationwide for
      investigation of enteric pathogens or diarrhoea were screened with real-time PCR
      for the presence of the Shiga toxin genes. Patients were selected if their stool
      contained blood upon macroscopic examination, if they had a history of bloody
      diarrhoea, were diagnosed with haemolytic uraemic syndrome, or were aged <6 years
      (irrespective of the bloody aspect of the stool). PCR-positive stools were
      forwarded to a central laboratory for STEC isolation and typing. In total, 4069
      stools were examined, with 68 (1.7%) positive PCR results. The highest prevalence
      was for stools containing macroscopic blood (3.5%), followed by stools from
      patients with a history of bloody diarrhoea (2.4%). Among young children, the
      prevalence (1.0%) was not significantly higher than among random, non-bloody,
      stool samples from diarrhoeal patients (1.4%). STEC strains were isolated from 25
      (38%) PCR-positive stools. Eleven O-serogroups were detected, including five STEC
      O157 strains. As serogroup O157 represented only 20% of the STEC isolates,
      laboratories should be encouraged to use techniques enabling them to detect non
      O157 serogroups, in parallel with culture, for isolation and subsequent
      characterisation of STEC strains for public health surveillance and detection of
      outbreaks.

PMID- 18325040
TI  - Evaluation of a novel internally controlled real-time PCR assay targeting the 16S
      rRNA gene for confirmation of Neisseria gonorrhoeae infections.
AB  - A novel HybProbe real-time LightCycler PCR assay was developed for confirmation
      of Neisseria gonorrhoeae in samples positive according to the COBAS AMPLICOR
      Chlamydia trachomatis/Neisseria gonorrhoeae PCR assay. The new assay amplifies
      375 bp of the N. gonorrhoeae 16S rRNA gene and includes an internal amplification
      control introduced during DNA purification. The assay had 100% specificity
      because of the high specificity of the HybProbes and primers. Other Neisseria
      spp. failed to generate positive crossing-point values and melting peaks. The
      analytical sensitivity for N. gonorrhoeae DNA was 0.5 fg/PCR, corresponding to
      0.3 CFU/PCR. Sensitivity was not impaired in the presence of higher DNA
      concentrations (>or=1000-fold) from Neisseria spp. other than N. gonorrhoeae. The
      sensitivity was similar to that reported for the COBAS AMPLICOR assay with
      cervical swab samples. To assess its clinical applicability as a confirmatory
      test, 38 (2.9%) of 1313 swabs that were positive according to the COBAS AMPLICOR
      assay were tested using the new in-house assay and the commercially available
      GenFlow Neisseria test. Twenty-one samples negative according to COBAS AMPLICOR
      also underwent confirmatory testing. Both confirmatory tests yielded identical
      results; the 21 negative samples remained negative, and only 11 (28.9%) of the
      samples positive according to COBAS AMPLICOR were positive after retesting,
      suggesting a low prevalence (0.84%) of N. gonorrhoeae infection in the study
      population. These data suggest that the novel real-time PCR assay is an excellent
      and easy to interpret confirmatory test for the existing COBAS AMPLICOR assay for
      N. gonorrhoeae.

PMID- 18325041
TI  - Mapping of a new autosomal recessive non-syndromic hearing impairment locus
      (DFNB45) to chromosome 1q43-q44.

PMID- 18325042
TI  - Three novel mutations in the PORCN gene underlying focal dermal hypoplasia.
AB  - Focal dermal hypoplasia (FDH) is an X-linked dominant disorder characterized by
      patchy dermal hypoplasia with digital, ocular and dental abnormalities. Very
      recently, mutations in the PORCN gene were demonstrated to cause FDH. Here, we
      described three unrelated Thai girls who were sporadic cases of FDH. One of them
      had unilateral athelia, which has never been described in FDH. Mutation analysis
      by polymerase chain reaction sequencing the entire coding regions of PORCN
      successfully revealed three potentially pathogenic mutations, c.373+1G>A,
      c.737_738insA and c.1094G>A (p.R365Q). One was found in each of three patients.
      In addition, another sequence variant c.682C>T (p.R228C) with an inconclusive
      role was found in one patient and her unaffected mother. The two missense
      mutations were not detected in at least 100 ethnic-matched control chromosomes,
      and all four mutations had never been previously described. X chromosome
      inactivation studies showed random patterns in all of them. This study
      demonstrates that PORCN is the gene responsible for FDH across different
      populations and extends the total number of confirmed mutations to 26.

PMID- 18325043
TI  - Striking a balance between biodiversity conservation and socioeconomic viability
      in the design of marine protected areas.
AB  - The establishment of marine protected areas is often viewed as a conflict between
      conservation and fishing. We considered consumptive and nonconsumptive interests
      of multiple stakeholders (i.e., fishers, scuba divers, conservationists,
      managers, scientists) in the systematic design of a network of marine protected
      areas along California's central coast in the context of the Marine Life
      Protection Act Initiative. With advice from managers, administrators, and
      scientists, a representative group of stakeholders defined biodiversity
      conservation and socioeconomic goals that accommodated social needs and conserved
      marine ecosystems, consistent with legal requirements. To satisfy biodiversity
      goals, we targeted 11 marine habitats across 5 depth zones, areas of high species
      diversity, and areas containing species of special status. We minimized adverse
      socioeconomic impacts by minimizing negative effects on fishers. We included fine
      scale fishing data from the recreational and commercial fishing sectors across 24
      fisheries. Protected areas designed with consideration of commercial and
      recreational fisheries reduced potential impact to the fisheries approximately
      21% more than protected areas designed without consideration of fishing effort
      and resulted in a small increase in the total area protected (approximately
      3.4%). We incorporated confidential fishing data without revealing the identity
      of specific fisheries or individual fishing grounds. We sited a portion of the
      protected areas near land parks, marine laboratories, and scientific monitoring
      sites to address nonconsumptive socioeconomic goals. Our results show that a
      stakeholder-driven design process can use systematic conservation-planning
      methods to successfully produce options for network design that satisfy multiple
      conservation and socioeconomic objectives. Marine protected areas that
      incorporate multiple stakeholder interests without compromising biodiversity
      conservation goals are more likely to protect marine ecosystems.

PMID- 18325044
TI  - Radiotherapy in rectal cancer: is it time for change? A qualitative analysis of
      the national questionnaire survey of members of ACPGBI on preliminary CRO7
      results.
AB  - BACKGROUND: A national questionnaire survey on management of rectal cancer
      suggested that despite the evidence of the CRO7 trial supporting the use of
      neoadjuvant short-course radiotherapy for operable rectal cancer, approximately
      two-thirds of consultant surgeons in the UK still have to implement this
      treatment regime routinely. However, 39% of surgeons have changed their practice
      following the early dissemination of trial results. Change in clinical practice
      is driven by a number of factors. AIM: To determine factors influencing changing
      clinical practice in the use of radiotherapy in rectal cancer. METHOD: A 14-item
      questionnaire was designed to inquire into the current management strategy of
      operable rectal cancer and the possible role of neoadjuvant radiotherapy. A
      postal questionnaire survey was sent to all the active consultant members of the
      Association of Coloproctology of Great Britain and Ireland. Data for this article
      have been drawn from the subset of results constituting the comments section in
      the questionnaire. Qualitative methodology was adopted to analyse the comments
      section. RESULTS: Of 400 questionnaires, 200 (50%) were returned completed. Of
      these, only 52 (26%) surgeons completed the comments section. Themes that emerged
      from thematic analysis were: Patient groups, Treatment, Evidence-based practice
      (EBP), Professional consensus and Service provisions. The derived outcomes were:
      individualization of treatment, safer and less harmful treatment, increased role
      of multidisciplinary teams, need to increase awareness of the current evidence
      based literature, develop protocols and guidelines along with shortening the
      delay in implementing EBP and good service provisions. CONCLUSION: In conclusion,
      change in practice is a slow and complex process influenced not only by data and
      scientific evidence, but also by a combination of other factors. Some of them are
      Clinical decision making, EBP/Education, Research Translation and Organizational
      factors with Infrastructure/Resources. Some of the above-mentioned conclusions
      will aid the policy makers and the opinion leaders in the National Health Service
      (NHS).

PMID- 18325045
TI  - Ileostomy revision using noncutting linear stapler.
AB  - OBJECTIVE: The study aimed to evaluate the outcome of ileostomy revision for
      retraction and prolapse using noncutting linear stapler. METHOD: Forty five
      patients undergoing a total of 94 stapled revisions between 1.1.1995 and
      31.12.2005 were identified by the unique code for stomal revision. Medical
      records for all patients were examined. RESULTS: Thirty-five (77.8%) of the 45
      patients were women. In 43 (95.6%), the indication was stomal retraction. Median
      follow-up was 28 months (2-122). One or more stapling procedures resulted in a
      normal stoma at follow-up in 18 (41.9%) of 43 patients treated for stomal
      retraction. When other types of repair were included, a normal stoma was achieved
      in 30 (69.8%) of 43 patients. Patients with a low BMI had the lowest success rate
      (44%), but none of the possible factors analysed for influence on success had a
      statistically significant impact. Two patients were treated for prolapse, and
      both needed other types of revision. CONCLUSIONS: Stapled ileostomy revision is
      easy to perform and has a low morbidity. Less than half the patients achieve a
      satisfactory long-term result after one or more stapling procedures. Many
      patients still benefit from other types of revision when stapling has failed.

PMID- 18325046
TI  - Expression of vasohibin as a novel endothelium-derived angiogenesis inhibitor in
      endometrial cancer.
AB  - We have previously reported on vasohibin as a novel endothelium-derived vascular
      endothelial growth factor (VEGF)-inducible inhibitor of angiogenesis. The aim of
      our present study was to define the role of vasohibin in endometrioid endometrial
      adenocarcinoma. We collected 78 sections of endometrial carcinoma for assessment
      using immunohistochemistry. Twenty-seven were well differentiated (G1), 25 were
      moderately differentiated (G2), and 26 were poorly differentiated endometrioid
      adenocarcinomas (G3). We also included 12 sections of normal cyclic endometria,
      six of which were in the proliferative phase and six were in the secretory phase.
      We investigated the expression of vasohibin, and compared it to VEGF receptor-2
      (VEGFR-2: KDR/flk-1), CD34, Ki-67, VEGF-A, and D2-40 (as a lymphatic vessel
      marker). We assessed the ratio of vasohibin- and VEGFR-2-positive vessels in the
      stroma of endometrial carcinoma. Immunohistochemical assessment was classified as
      negative or positive based on staining intensity. Vasohibin was selectively
      expressed on vascular endothelial cells in both cyclic endometria and endometrial
      carcinomas. Vasohibin was highly expressed in the normal functional endmetrium of
      the secretory phase, especially in the spiral artery, and was highly expressed in
      all grades of endometrioid adenocarcinomas. The stromal endothelial cells in G3
      expressed vasohibin and VEGFR-2 more frequently than these in G1. In endometrioid
      adenocarcinomas, there was a significant correlation between the expression
      percentage of vasohibin and that of VEGFR-2 (P < 0.0001, r(2) = 0.591). This is
      the first study to elucidate the correlation between expression of vasohibin in
      the stromal endothelial cells and that of VEGFR-2 in human carcinomas.

PMID- 18325047
TI  - Functional analysis of individual cells and microenvironment of breast cancer
      draining lymph nodes.
AB  - The development of distant metastases is the major cause of death in breast
      cancer (BC). In many BC cases, metastases are present in patients with no
      metastasis-positive lymph nodes (LN). Hence, there is a need to improve prognosis
      by a better prediction of the nodal status and tumor spread. The current study is
      designed to develop and utilize new functional characteristics of the cells and
      microenvironment of BC-draining LN, which may help to improve the estimation of
      LN metastatic involvement. Innovative devices and methodologies were developed
      for collecting, transferring, and analyzing LN at an individual-cell resolution.
      Using these devices, a suspension of living cells were prepared from the LN and
      processed for various assays, including immunophenotypic analysis, activation
      status, and invasion activity. The functional profile of tumor-activated LN cells
      showed an increase in the intracellular enzymatic reaction rate, accompanied by a
      homogeneous distribution of transferrin receptor as well as by a significant
      increase in matrix metalloproteinase proteolytic activity. Moreover, the
      proportion of cells exhibiting such a profile was significantly higher in tumor
      containing LN than in tumor-free LN. Thus, the live and postfixation features of
      LN cells and their microenvironment, correlated with the functional status of the
      LN, may serve to improve their predictive value in breast cancer examination.

PMID- 18325048
TI  - Intratumor heterogeneity of epidermal growth factor receptor mutations in lung
      cancer and its correlation to the response to gefitinib.
AB  - Somatic mutations introduced into the epidermal growth factor receptor (EGFR)
      gene in non-small-cell lung cancer (NSCLC) are important factors to determine
      therapeutic responses to gefitinib. The current diagnostic test measures the
      overall EGFR mutation status of the cancer tissue, and may ignore the presence of
      non-mutated, gefitinib-unresponsive cancer cells. Twenty-one NSCLC patients with
      EGFR mutations were recruited for the study. All patients were treated with
      gefitinib after surgical treatment. Fifty to sixty areas of NSCLC tumors were
      sampled from each tissue, and their EGFR mutation states were determined by a
      primer extension assay. This assay discriminates between EGFR mutation-positive
      and -negative cancer cells within a single tumor tissue. Fifteen tissues
      consisted only of cells with EGFR mutations, but the remaining six tissues
      contained both mutated and non-mutated cells. Time to disease progression and
      overall survival after gefitinib treatment were significantly shorter in those
      patients with EGFR heterogeneity (P = 0.009 and P = 0.003, respectively). A
      considerable proportion of NSCLC contains a heterogeneous population of both EGFR
      mutated and non-mutated cancer cells, resulting in a reduced response to
      gefitinib. The intratumor genetic heterogeneity of a target molecule such as EGFR
      would be an important factor to consider when treating patients with molecular
      target agents.

PMID- 18325049
TI  - Chronic pain after vasectomy: a diagnostic and treatment dilemma.

PMID- 18325050
TI  - Predicting survival after radical cystectomy for bladder cancer.
AB  - Accurate prediction is essential for patient counselling, appropriate selection
      of treatments and determination of eligibility for clinical trials. In this
      review we assess the available determinants of oncological outcome after radical
      cystectomy (RC) for transitional cell carcinoma of the urinary bladder. We
      reviewed previous publications to provide guidelines in terms of criteria,
      limitations and clinical value of available tools for predicting patient outcome
      after RC. Our findings suggest that while individual surgical, patient and
      pathological features provide useful estimates of survival outcome, the inherent
      heterogeneity of tumour biology and patient characteristics leads to significant
      variation in outcome. By incorporating all relevant continuous predictive factors
      for individual patients, integrative predictive models, such as nomograms or
      artificial neural networks, provide more accurate predictions and generally
      surpass clinical experts at predicting outcomes. Nonetheless, there is a clear
      need for the development and validation of molecular biomarkers and their
      incorporation into multivariable predictive tools. Significant progress has been
      made in identifying important molecular markers of disease and the development of
      multifactorial tools for predicting the outcome after RC.

PMID- 18325051
TI  - A comparison of the performance of microsatellite and methylation urine analysis
      for predicting the recurrence of urothelial cell carcinoma, and definition of a
      set of markers by Bayesian network analysis.
AB  - OBJECTIVE: To compare the potential of two diagnostic methods for detecting
      recurrence of urothelial cell carcinoma (UCC) of the bladder, by (i) detecting
      alterations in microsatellite DNA markers and loss of heterozygosity (LOH), and
      (ii) detecting aberrant gene hypermethylation, as UCC has a high recurrence rate
      in the urinary tract and the disease can invade muscle if new tumours are
      overlooked. PATIENTS AND METHODS: Over 1 year, urine samples were retrieved from
      40 patients already diagnosed with bladder UCC (30 pTa, two pTis, eight pT1).
      Samples were collected 6 months after bladder tumour resection, during the follow
      up schedule. We used samples to analyse nine microsatellite markers and the
      methylation status of 11 gene promoters. Receiver operating characteristic curves
      were generated and Bayesian statistics used to create an interaction network
      between recurrence and the biomarkers. RESULTS: During the study, 15 of the 40
      patients (38%) had a tumour recurrence and 14 were identified by cystoscopy
      (reference method). Overall, microsatellite markers (area under curve, AUC 0.819,
      95% confidence interval, CI, 0.677-0.961) had better performance characteristics
      than promoter hypermethylation (AUC 0.448, 0.259-0.637) for detecting recurrence.
      A marker panel of IFNA, MBP, ACTBP2, D9S162 and of RASSF1A, and WIF1 generated a
      higher diagnostic accuracy of 86% (AUC 0.92, 0.772-0.981). CONCLUSION:
      Microsatellite markers have better performance characteristics than promoter
      hypermethylation for detecting UCC recurrence. These data support the further
      development of a combination of only six markers from both methods in urinary
      DNA. Once validated, it could be used routinely during the follow-up for the
      early detection and surveillance of UCC from the lower and upper urinary tract.

PMID- 18325052
TI  - Implications of mismatch repair genes hMLH1 and hMSH2 in patients with sporadic
      renal cell carcinoma.
AB  - OBJECTIVES: To analyse the implications of DNA mismatch repair genes hMLH1 and
      hMSH2 in sporadic renal cell carcinoma (RCC). MATERIALS AND METHODS: Specimens of
      tumour and healthy renal tissue were collected from 89 patients treated for
      sporadic RCC. Another 95 blood samples taken from individuals with no history of
      cancer were also analysed. After DNA extraction and PCR amplification,
      microsatellite instability (MSI) was determined using the Bethesda microsatellite
      panel, two exonic microsatellites of the TGFbRII and BAX genes, and the
      microsatellite D3S1611. The promoter methylation status of hMLH1 was investigated
      using the HpaII and MspI restriction enzymes. In addition, a sequencing analysis
      of complete coding region of hMLH1 and hMSH2 genes was performed. RESULTS: MSI
      and promoter hypermethylation of hMLH1 were not detected. Interestingly, loss of
      heterozygosity (LOH) was common among patients with RCC, particularly in
      microsatellite D3S1611 (34.9%). Mutations were identified in eight patients:
      K618A and V716M in gene hMLH1; and I145V, G322D, and the novel mutation P349A, in
      gene hMSH2. The mutations also appeared in healthy renal tissue and therefore,
      were considered as germline DNA sequence variations. There were G322D and K618A
      changes in >1% of the healthy control subjects, suggesting that they are DNA
      polymorphisms. CONCLUSIONS: Our data show that loss of function of both hMLH1 and
      hMSH2 is not involved in sporadic RCC, either by promoter methylation or mutation
      in their exons. However, LOH indicated that chromosomal instability affecting
      large fragments of DNA was the main genetic alteration we detected associated
      with RCC.

PMID- 18325053
TI  - Retroperitoneal lymph node dissection after chemotherapy for germ cell tumours:
      is a full bilateral template always necessary?
AB  - OBJECTIVE: To evaluate the long-term oncological outcome in selected patients
      treated for nonseminomatous germ cell tumours (NSGCT) with a retroperitoneal
      lymph node dissection after chemotherapy (pcRPLND) and not using the full
      bilateral template. PATIENTS AND METHODS: From 1988 to 2005, 102 patients with
      retroperitoneal stage II NSGCT, who at initial presentation had metastases in the
      primary retroperitoneal site only, had pcRPLND within a restricted template,
      whether computed tomography showed complete or incomplete remission. In all, 78
      patients had a unilateral template dissection and 24 an open modified template
      dissection. RESULTS: Of the 102 patients, 30 had stage IIC, 63 IIB, and nine
      tumour marker-positive stage IIA disease. Active tumour was found in two RPLND
      specimens; mature teratoma in 46 of the 102 patients, and necrosis/fibrosis in
      54. Antegrade ejaculation was preserved in all 78 patients who had unilateral
      RPLND and in 18 of 24 who had a modified RPLND (overall antegrade ejaculation
      rate 94%). During a median follow-up of 102 months there were only three
      recurrences, two outside the retroperitoneum and one in the retroperitoneum. Only
      the latter was retrocaval, above the level of the inferior mesenteric artery
      within the boundaries of a full bilateral RPLND. This patient had had left
      unilateral template dissection after chemotherapy for IIC disease which was
      restricted to the para-aortic nodes. CONCLUSION: In a selected group of patients
      with stage II NSGCT, pcRPLND within the modified template might be oncologically
      efficient and allow ejaculation to be preserved.

PMID- 18325054
TI  - Effect of extracellular ATP on the growth of hormone-refractory prostate cancer
      in vivo.
AB  - OBJECTIVE: To investigate whether the antineoplastic action of ATP on hormone
      refractory prostate carcinoma (HRPC) cells in vitro also occurs in vivo, by
      examining the effect of ATP in vivo on tumours resulting from implanted HRPC
      cells in mice. MATERIALS AND METHODS: HRPC tumour cells DU145 and PC-3 were
      implanted into male nude athymic mice. The effect of daily intraperitoneal (i.p.)
      injections of ATP (25 mm) on the growth of freshly implanted and established HRPC
      tumours was assessed. Histological examination using light and electron
      microscopy was used to confirm retention of the original ultrastructure of the
      implanted tumours. RESULTS: Daily i.p. injections of ATP significantly reduced
      the growth of freshly implanted DU145 tumour by 57.8% (P = 0.003), and reduced
      the rate of growth of established DU145 tumour by 69.0% (P = 0.006). ATP also
      significantly reduced the growth of freshly implanted PC-3 tumour by 68.9% (P <
      0.001). ATP treatment had no adverse effects on the host mice. CONCLUSION: Our
      results show, for the first time, that ATP effectively reduces the growth of
      advanced HRPC tumours in vivo. This may represent a step in establishing ATP as
      an effective agent for HRPC treatment.

PMID- 18325055
TI  - The management of genital lymphoedema.
AB  - OBJECTIVES: To report our experience and management of genital lymphoedema, as
      this condition can be extremely debilitating and difficult to manage. PATIENTS
      AND METHODS: The clinical records of 90 patients with genital lymphoedema who
      presented between 1998 and 2007 were retrospectively reviewed. The surgical
      management of 34 patients consisted of the excision of the affected skin and of
      the subcutaneous layers. This involved scrotal excision in 15 patients with
      primary closure. Skin grafts were required in seven patients for penile shaft
      cover. The results for cosmesis, recovery of sexual function, patient's
      satisfaction and complications are discussed. RESULTS: In all, 56 patients were
      successfully managed conservatively by treating the underlying condition,
      antibiotic administration, compression and elevation of the genitalia. The
      remaining 34 patients required surgical management with an overall excellent
      cosmetic result and a significant improvement in sexual function. CONCLUSIONS:
      When surgery is necessary for genital lymphoedema, the new techniques described
      provide excellent cosmetic and functional results.

PMID- 18325056
TI  - Clinical relevance of health-related quality of life outcomes with darifenacin.
AB  - OBJECTIVE: To determine the clinical relevance of changes in health-related
      quality of life (HRQoL) in patients with overactive bladder (OAB) treated with
      darifenacin. PATIENTS AND METHODS: Data were pooled from three randomized,
      placebo-controlled, parallel-group, fixed-dose, 12-week studies. After 2-week
      washout, treatment-free or placebo run-in periods, patients with OAB (n = 1059;
      85% women; age 19-88 years) were randomized to 12 weeks' treatment with
      darifenacin controlled-release 7.5 mg (n = 337) or 15 mg once daily (n = 334) or
      placebo (n = 388). The King's Health Questionnaire (KHQ) was used to assess HRQoL
      at baseline and Week 12. The clinical significance of changes in KHQ domain
      scores was assessed using the concept of minimum important difference (MID),
      using two different methods. RESULTS: Darifenacin treatment was associated with
      significantly greater improvements than placebo in six primary KHQ domain scores
      known to be of importance to patients with OAB. In addition, a significantly
      greater proportion of darifenacin-treated patients met or exceeded reference MID
      vs placebo in these domains (Incontinence Impact, Severity Measures, Role
      Limitations, Social Limitations, Emotions and Physical Limitations; P = 0.01). In
      darifenacin-treated patients, there were significant correlations between the
      reductions in incontinence episodes per week and improvements in KHQ scores (P <
      0.001). The strongest correlations were in the Incontinence Impact, Social
      Limitations, Role Limitations, Severity Measures and Emotions domains.
      CONCLUSIONS: Darifenacin treatment was associated with significant, clinically
      relevant improvements in HRQoL in patients with OAB, shown using the concept of
      MID to interpret change in KHQ scores.

PMID- 18325057
TI  - High-intensity focused ultrasound in prostate cancer; a systematic literature
      review of the French Association of Urology.
AB  - We discuss the efficacy and safety of high-intensity focused ultrasound (HIFU) in
      patients with prostate cancer, to define the best indications for HIFU in daily
      clinical practice as primary therapy. We searched Medline and Embase for clinical
      studies evaluating the efficacy and safety of HIFU in prostate cancer (July
      2007), and abstracts presented at the 2005-2007 annual meetings of the European
      Association of Urology and American Urological Association were screened. In all,
      37 articles/abstracts were selected. As the data on HIFU as salvage therapy were
      limited, we focused on HIFU as primary therapy. Studies consisted of case series
      only. Included patients were approximately 70 years old with T1-T2 N0M0 disease,
      Gleason Score <or=7, a prostate-specific antigen (PSA) level of <or=28 ng/mL and
      a prostate volume of <or=40 mL. Negative biopsy rates with the Ablatherm device
      (EDAP TMS S.A., Vaulx-en-Velin, France) were 64-93%, and a PSA nadir of <or=0.5
      ng/mL was achieved in 55-84% of patients. The 5-year actuarial disease-free
      survival rates were 60-70%. The most common complications were stress urinary
      incontinence, urinary tract infection, urethral/bladder neck stenosis or
      strictures, and erectile dysfunction. For the Ablatherm device, the rate of
      complications has been significantly reduced over the years, due to technical
      improvements in the device and the use of transurethral resection of the prostate
      before HIFU. In conclusion, HIFU as primary therapy for prostate cancer is
      indicated in older patients (>or=70 years) with T1-T2 N0M0 disease, a Gleason
      score of <7, a PSA level of <15 ng/mL and a prostate volume of <40 mL. In these
      patients HIFU achieves short-term cancer control, as shown by a high percentage
      of negative biopsies and significantly reduced PSA levels. The median-term
      survival data also seem promising, but long-term follow-up studies are needed to
      further evaluate cancer-specific and overall survival rates before the
      indications for primary therapy can be expanded.

PMID- 18325058
TI  - The lymph node yield during robot-assisted radical cystectomy.
AB  - OBJECTIVE: To evaluate the lymph node yield (LNY) during robot-assisted radical
      cystectomy (RC), as it has been questioned as to whether robot assistance allows
      adequate pelvic LN dissection (LND), especially during the initial experience.
      PATIENTS AND METHODS: In all, 67 consecutive patients were selected for robot
      assisted RC and LND with open urinary diversion from October 2005 to November
      2007. Data was collected prospectively in a standard fashion as part of a quality
      assurance programme. Nine patients were excluded (three had unresectable disease
      and six underwent palliative cystectomy) and the remainder were divided into five
      groups. Data included demographics, operative variables, complications and
      pathological outcomes. Evidence of the LNY curve was examined using nonlinear
      regression to compare the number of LNs obtained. RESULTS: The mean (range)
      patient age was 67 (36-90) years and the mean body mass index (BMI) was 27 (17
      45) kg/m(2). The mean operative duration for the robot-assisted pelvic LND was 44
      (19-85) min. There was one postoperative complication that required exploration
      for vascular injury. The mean number of LNs retrieved was 18 (6-43). The mean LNY
      for each of the five groups was 13, 16, 21, 19 and 23, respectively, and neither
      BMI nor previous major abdominal surgery affected LNY. CONCLUSION: Robot-assisted
      RC with pelvic LND was performed safely. LNY was oncologically acceptable and
      increased with experience.

PMID- 18325059
TI  - Single-incision laparoscopic surgery: initial urological experience and
      comparison with natural-orifice transluminal endoscopic surgery.
AB  - Laparoscopic approaches have increasingly assumed a central role in the
      management of benign and malignant surgical diseases. While laparoscopy is less
      morbid than open surgery, it still requires several incisions, each > or =1-2 cm
      long. Each incision risks morbidity from bleeding, hernia and/or internal organ
      damage, and incrementally decreases cosmesis. An alternative to conventional
      laparoscopy is single-incision laparoscopic surgery (SILS), in which articulating
      or bent instrumentation with specialized multi-lumen ports is used. These
      technical innovations obviate the need to externally space trocars for
      triangulation, thus allowing the creation of a small, solitary portal of entry
      into the abdomen. Laboratory and early clinical series showed the feasibility as
      well as safe and successful completion of SILS. Natural-orifice transluminal
      endoscopic surgery (NOTES) is another exciting development in minimally invasive
      urology, but existing flexible endoscopes and instruments are limited in
      providing a platform for this form of advanced surgery, resulting in the slow
      adoption of NOTES. Future work is needed to improve existing instrumentation,
      increase clinical experience, assess the benefits of both surgical approaches,
      and explore other potential applications for these novel techniques.

PMID- 18325060
TI  - Single-port laparoscopic surgery: initial experience in children for
      varicocelectomy.
AB  - OBJECTIVE: To present our initial experience in children undergoing single-port
      laparoscopic varicocelectomy (SPLV) using a new approach in which the entire
      procedure is performed through a multichannel single laparoscopic port inserted
      in the umbilicus rather than the traditional LV performed through three abdominal
      ports. PATIENTS AND METHODS: We reviewed our experience with all paediatric
      patients who had undergone transumbilical SPLV [Uni-X Single Port Access
      Laparoscopic System, Pnavel Systems, NJ, USA]. This novel 20-mm laparoscopic port
      has three working channels and gas insufflation access. The system also includes
      a variety of curved laparoscopic instruments that can be introduced through the
      SP. A Hassan technique through an incision within the inferior aspect of the
      umbilicus is used to obtain laparoscopic port access to the abdominal cavity. The
      SP is then fixed into position with pre-placed rectus facial sutures. Using a
      curved laparoscopic grasper and scissors, an incision is made within the
      posterior peritoneum on the medial and lateral aspects of the left testicular
      artery and veins, proximal to the vas deferens. The vessels, both artery and
      veins, are transected leaving clips both proximally and distally. RESULTS:
      Transumbilical SPLV was completed in three consecutive adolescents (aged 13, 15
      and 16 years) without placing any additional ports or conversion to open surgery.
      All procedures were performed for left-sided grade III varicoceles. The operative
      duration was <1 h for each procedure. All patients were discharged on the same
      day as their surgery and none required re-hospitalization. At a mean (range)
      follow-up of 8.7 (6-10) weeks there was a good cosmetic result, with no
      varicocele recurrence, or intraoperative or postoperative complications including
      wound infection, hydrocele, or incision site herniation. CONCLUSION: We report
      the first use of a multicannula single laparoscopic port in children and for
      SPLV. This new laparoscopic approach, similar to any new technique, requires
      further experience to fully evaluate its benefits and limitations.

PMID- 18325061
TI  - Intensifying the saturation biopsy technique for detecting prostate cancer after
      previous negative biopsies: a step in the wrong direction.
AB  - OBJECTIVE: To report the results using an extensive saturation biopsy in men with
      negative prostate biopsies but in whom there is still a clinical suspicion for
      carcinoma. PATIENTS AND METHODS: Between February 1999 and October 2004 we
      offered 40 patients (median age 63 years) an extensive saturation biopsy if there
      was clinical suspicion of prostate cancer after previous negative prostate
      biopsies. The median (range) number of cores taken was 64 (39-139) and was
      adjusted to the size of the prostate. All patients received general or spinal
      anaesthesia. RESULTS: Of the 40 patients, 18 (45%) had carcinoma in at least one
      core; 16 had a radical prostatectomy, which showed pT2a, pT2b, pT2c, pT3a and
      pT3b adenocarcinoma of the prostate in three, four, six, two and one patients,
      respectively. Brachytherapy and external radiation were the therapies of choice
      in the other patients. Sixteen patients had marked haematuria after the biopsy
      procedure. CONCLUSION: There is no significant increase in the cancer detection
      rate in an extensive saturation-biopsy regimen compared to published series with
      fewer cores, but the morbidity increased.

PMID- 18325062
TI  - Active surveillance: a safe, low-cost prognostic test for prostate cancer.

PMID- 18325063
TI  - Tamsulosin: ureteric motility.

PMID- 18325064
TI  - The morbidity of transperineal template-guided prostate mapping biopsy.
AB  - OBJECTIVE: To evaluate the effect of transperineal template-guided prostate
      mapping biopsy (TTMB) on urinary, bowel and erectile function. PATIENTS AND
      METHODS: In all, 129 men had TTMB; a median of 56 biopsy cores were obtained per
      patient. Tamsulosin (0.8 mg daily) was initiated 2 days before TTMB and continued
      for 2 weeks. The International Prostate Symptom Score (IPSS), Rectal Function
      Assessment Score (R-FAS), International Index of Erectile Function (IIEF)-6 and
      the postvoid residual volume (PVR) were assessed at baseline and after 30 days,
      except for the IPSS, which was also assessed at 7 days. Several variables were
      evaluated as predictors of TTMB-induced morbidity. RESULTS: The mean patient age
      was 64.7 years with a mean prostate volume of 74.3 mL; 60 men (46.5%) were
      diagnosed with prostate cancer. After TTMB, 39.4%, 7.1% and 1.6% of patients
      remained catheter-dependent at 0, 3 and 6 days. The median catheter-dependency
      was 0, 1, 2 and 3 days for prostate volumes of <60, 60-90, 90-120 and >120 mL,
      respectively. No patient remained catheter- dependent for >12 days or required a
      transurethral resection secondary to TTMB. The mean IPSS before TTMB was 10.4,
      and was 4.6 and 3.8 at 7 and 30 days. At baseline and 30 days the mean PVR was 35
      and 40 mL, and the median R-FAS and IIEF scores for patients potent before TTMB
      were 2.0 and 2.2, and 27.0 and 26.0, respectively. CONCLUSIONS: TTMB is a
      promising procedure for diagnosing prostate cancer. TTMB-related morbidity
      differs from that of standard TRUS biopsy primarily in the incidence of temporary
      urinary retention, and is comparable in terms of urinary, bowel and erectile
      function.

PMID- 18325065
TI  - Bortezomib-induced reversible posterior leucoencephalopathy syndrome.

PMID- 18325066
TI  - A flexible approach to measurement error correction in case-control studies.
AB  - SUMMARY: We investigate the use of prospective likelihood methods to analyze
      retrospective case-control data where some of the covariates are measured with
      error. We show that prospective methods can be applied and the case-control
      sampling scheme can be ignored if one adequately models the distribution of the
      error-prone covariates in the case-control sampling scheme. Indeed, subject to
      this, the prospective likelihood methods result in consistent estimates and
      information standard errors are asymptotically correct. However, the distribution
      of such covariates is not the same in the population and under case-control
      sampling, dictating the need to model the distribution flexibly. In this article,
      we illustrate the general principle by modeling the distribution of the
      continuous error-prone covariates using the skewnormal distribution. The
      performance of the method is evaluated through simulation studies, which show
      satisfactory results in terms of bias and coverage. Finally, the method is
      applied to the analysis of two data sets which refer, respectively, to a
      cholesterol study and a study on breast cancer.

PMID- 18325067
TI  - Analyzing complex capture-recapture data in the presence of individual and
      temporal covariates and model uncertainty.
AB  - SUMMARY: We consider the issue of analyzing complex ecological data in the
      presence of covariate information and model uncertainty. Several issues can arise
      when analyzing such data, not least the need to take into account where there are
      missing covariate values. This is most acutely observed in the presence of time
      varying covariates. We consider mark-recapture-recovery data, where the
      corresponding recapture probabilities are less than unity, so that individuals
      are not always observed at each capture event. This often leads to a large amount
      of missing time-varying individual covariate information, because the covariate
      cannot usually be recorded if an individual is not observed. In addition, we
      address the problem of model selection over these covariates with missing data.
      We consider a Bayesian approach, where we are able to deal with large amounts of
      missing data, by essentially treating the missing values as auxiliary variables.
      This approach also allows a quantitative comparison of different models via
      posterior model probabilities, obtained via the reversible jump Markov chain
      Monte Carlo algorithm. To demonstrate this approach we analyze data relating to
      Soay sheep, which pose several statistical challenges in fully describing the
      intricacies of the system.

PMID- 18325068
TI  - Combining multiple biomarker models in logistic regression.
AB  - In medical research, there is great interest in developing methods for combining
      biomarkers. We argue that selection of markers should also be considered in the
      process. Traditional model/variable selection procedures ignore the underlying
      uncertainty after model selection. In this work, we propose a novel model
      combining algorithm for classification in biomarker studies. It works by
      considering weighted combinations of various logistic regression models; five
      different weighting schemes are considered in the article. The weights and
      algorithm are justified using decision theory and risk-bound results. Simulation
      studies are performed to assess the finite-sample properties of the proposed
      model-combining method. It is illustrated with an application to data from an
      immunohistochemical study in prostate cancer.

PMID- 18325069
TI  - An enhanced quantile approach for assessing differential gene expressions.
AB  - Due to the small number of replicates in typical gene microarray experiments, the
      performance of statistical inference is often unsatisfactory without some form of
      information-sharing across genes. In this article, we propose an enhanced
      quantile rank score test (EQRS) for detecting differential expression in GeneChip
      studies by analyzing the quantiles of gene intensity distributions through probe
      level measurements. A measure of sign correlation, delta, plays an important role
      in the rank score tests. By sharing information across genes, we develop a
      calibrated estimate of delta, which reduces the variability at small sample
      sizes. We compare the EQRS test with four other approaches for determining
      differential expression: the gene-specific quantile rank score test, the quantile
      rank score test assuming a common delta, a modified t-test using summarized probe
      set-level intensities, and the Mack-Skillings rank test on probe-level data. The
      proposed EQRS is shown to be favorable for preserving false discovery rates and
      for being robust against outlying arrays. In addition, we demonstrate the merits
      of the proposed approach using a GeneChip study comparing gene expression in the
      livers of mice exposed to chronic intermittent hypoxia and of those exposed to
      intermittent room air.

PMID- 18325070
TI  - A two-stage stepwise estimation procedure.
AB  - This article proposes a two-stage simultaneous confidence procedure for the
      comparisons of k pairs of population means, without using multiplicity adjustment
      of more than two populations. The proposed procedure can be broadly applied to
      parametric or nonparametric models. It is robust and versatile because its
      derivation only utilizes a partitioning approach in conjunction with a bivariate
      adjustment, without any assumption on the underlying distribution. To elucidate
      the application, the proposed procedure is intertwined with the estimation of the
      therapeutic window of a drug. It provides confidence limits for the efficacy and
      the toxicity of the effective doses, highest ineffective dose, safe doses, and
      lowest unsafe dose, simultaneously. Such estimation information facilitates
      follow-up studies in clinical trials. As an illustrative example, the new
      procedure is applied to analyze a data set on molecular cancer therapeutics
      regarding the apoptotic killing effects of different chemical compounds on two
      leukemia cell lines.

PMID- 18325071
TI  - Population size estimation in a two-list surveillance system with a discrete
      covariate.
AB  - Capture-recapture methods are widely adopted to estimate sizes of populations of
      public health interest using information from surveillance systems. For a two
      list surveillance system with a discrete covariate, a population is divided into
      several subpopulations. A unified framework is proposed in which the logits of
      presence probabilities are decomposed into case effects and list effects. The
      estimators for the whole population and subpopulation sizes, their adjusted
      versions, and asymptotic standard errors admit closed-form expressions.
      Asymptotic and bootstrap individual and simultaneous confidence intervals are
      easily constructed. Conditional likelihood ratio tests are used to select one
      from three possible models. Real examples are investigated.

PMID- 18325072
TI  - A nonparametric mean estimator for judgment poststratified data.
AB  - MacEachern, Stasny, and Wolfe (2004, Biometrics60, 207-215) introduced a data
      collection method, called judgment poststratification (JPS), based on ideas
      similar to those in ranked set sampling, and proposed methods for mean estimation
      from JPS samples. In this article, we propose an improvement to their methods,
      which exploits the fact that the distributions of the judgment poststrata are
      often stochastically ordered, so as to form a mean estimator using isotonized
      sample means of the poststrata. This new estimator is strongly consistent with
      similar asymptotic properties to those in MacEachern et al. (2004). It is shown
      to be more efficient for small sample sizes, which appears to be attractive in
      applications requiring cost efficiency. Further, we extend our method to JPS
      samples with imprecise ranking or multiple rankers. The performance of the
      proposed estimators is examined on three data examples through simulation.

PMID- 18325073
TI  - A finite-state continuous-time approach for inferring regional migration and
      mortality rates from archival tagging and conventional tag-recovery experiments.
AB  - Spatially structured population dynamics models are important management tools
      for harvested, highly mobile species and although conventional tag recovery
      experiments remain useful for estimation of various demographic parameters of
      these models, archival tagging experiments are becoming an important data source
      for analyzing migratory behavior of mobile marine species. We provide a
      likelihood-based approach for estimating the regional migration and mortality
      rate parameters intrinsic to these models that may use information obtained from
      conventional tag recovery and archival tagging experiments. Specifically, we
      assume that the regional location and survival of animals through time is a
      finite-state continuous-time stochastic process. The stochastic process is the
      basis of probability models for observations provided by the different types of
      tags. Results from application to simulated tagging experiments for western
      Atlantic bluefin tuna show that maximum likelihood estimators based on archival
      tagging observations and corresponding confidence intervals perform similar to
      conventional tagging observations for a given number of tag releases and
      releasing tags in each region can improve the behavior of maximum likelihood
      estimators regardless of tag type. We provide an example application with
      Atlantic bluefin tuna released with conventional tags in 1990-1992.

PMID- 18325074
TI  - Generalized maximally selected statistics.
AB  - SUMMARY: Maximally selected statistics for the estimation of simple cutpoint
      models are embedded into a generalized conceptual framework based on conditional
      inference procedures. This powerful framework contains most of the published
      procedures in this area as special cases, such as maximally selected chi(2) and
      rank statistics, but also allows for direct construction of new test procedures
      for less standard test problems. As an application, a novel maximally selected
      rank statistic is derived from this framework for a censored response partitioned
      with respect to two ordered categorical covariates and potential interactions.
      This new test is employed to search for a high-risk group of rectal cancer
      patients treated with a neo-adjuvant chemoradiotherapy. Moreover, a new efficient
      algorithm for the evaluation of the asymptotic distribution for a large class of
      maximally selected statistics is given enabling the fast evaluation of a large
      number of cutpoints.

PMID- 18325075
TI  - Late-onset celecoxib-induced combined hepato-nephrotoxicity.

PMID- 18325076
TI  - Genetic profile of ischemic cerebrovascular disease and carotid stenosis.
AB  - OBJECTIVES: Carotid artery stenosis (CS) is a major risk factor for ischemic
      cerebrovascular disease (ICVD) and is therefore of interest in genetic
      investigating. Here we report the distribution of 100 polymorphisms in 47
      suspected susceptibility genes for ICVD and its risk factors. MATERIALS AND
      METHODS: Previously published markers in suspected susceptibility genes were
      genotyped in ICVD patients and controls (928/602). Genotyping was performed using
      multiplex polymerase chain reaction (PCR) and linear immobilized probe array
      assays. ICVD cases were subtyped according to Trial of Org 10172 in Acute Stroke
      Treatment (TOAST) or subdivided into CS and non-CS patients by ultrasonography in
      a separate analysis. RESULTS: Three polymorphisms located in the lipoprotein
      lipase (LPL), angiotensinogen (AGT) and guanine nucleotide-binding protein beta-3
      (GNB3) genes were significantly associated with ICVD after correction for age and
      gender. The strongest association was found for the protective LPL Ser447Term
      polymorphism. All the significant markers showed varying frequencies in different
      subphenotypes of ICVD. Factor VII, apolipoprotein E and two renin polymorphisms
      were differentially frequent in patients with evidence of CS compared with non-CS
      patients. CONCLUSIONS: We have found that some previously described
      susceptibility polymorphisms are weakly associated with ICVD and that subdivision
      of patients into CS and non-CS groups may help to identify new candidate
      polymorphisms.

PMID- 18325077
TI  - A high-affinity monoclonal anti-IgE antibody for depletion of IgE and IgE-bearing
      cells.
AB  - BACKGROUND: We have identified a monoclonal anti-human immunoglobulin E (IgE)
      antibody, which recognizes FcepsilonRI-bound IgE and prevents binding of IgE to
      FcepsilonRI. In this study, we assessed the binding kinetics and affinity of
      monoclonal antibody 12 (mAb12) for IgE and investigated whether mAb12 can be used
      for depletion of IgE and isolation of IgE-bearing cells from peripheral blood.
      METHODS: Binding kinetics and affinity for IgE were studied using Biacore surface
      plasmon resonance technique experiments. IgE antibodies were depleted from serum
      using sepharose-coupled mAb12 and IgE-bearing cells were enriched from
      heparinized blood samples with mAb12. The extent and biological relevance of IgE
      depletion were studied by quantitative IgE measurements and basophil histamine
      release experiments. Specific binding of mAb12 to IgE-bearing cells (basophils,
      mast cells, IgE-secreting plasma cells) was demonstrated by FACS. RESULTS:
      Monoclonal antibody 12 shows rapid association (k(a) = 5.46e5/Ms) with IgE,
      almost no dissociation (k(d) = 8.8e-5/s) and an affinity for IgE (K(D) = 1.61e-10
      M), which is as high as that of FcepsilonRI. Immobilized mAb12 could be used to
      deplete IgE antibodies and isolate IgE-bearing cells from peripheral blood in a
      single-step procedure. CONCLUSIONS: Monoclonal antibody 12 is a high affinity
      anti-human IgE antibody, which efficiently removes IgE and IgE-bearing cells from
      peripheral blood and may thus be used for extracorporeal depletion of IgE and IgE
      bearing cells.

PMID- 18325078
TI  - Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level
      replication after renal transplantation.
AB  - Human cytomegalovirus (HCMV) remains an important cause of morbidity after
      allotransplantation, causing a range of direct effects including hepatitis,
      pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is
      high level viral replication in blood but it remains unexplained why only a
      subset of patients develop such diseases. In this detailed study of 25 renal
      transplant recipients, we show that functional impairment of HCMV specific CD8 T
      cells in the production of interferon gamma was associated with a 14-fold
      increased risk of progression to high level replication. The CD8 T-cell
      impairment persisted during the period of high level replication and was more
      prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was
      also evident in dialysis patients. Threshold levels of functional impairment were
      associated with an increased risk of future HCMV replication and there was a
      direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells
      and HCMV load (R(2)= 0.83). These results help to explain why a subset of
      seropositive individuals develop HCMV replication and are at risk of end-organ
      disease and may facilitate the early identification of individuals who would
      benefit from targeted anti-HCMV therapy after renal transplantation.

PMID- 18325079
TI  - Liver transplantation for hepatopulmonary syndrome (HPS): what is the MESSAGE?

PMID- 18325080
TI  - Successful management of eviscerated renal allograft with preservation of
      function.
AB  - Although most wound complications after renal transplantation are minor, the
      renal allograft, in its superficial and extraperitoneal location, is vulnerable
      to exposure if there is wound breakdown resulting in loss of overlying tissue. We
      describe a 66-year-old man who received a renal allograft from a deceased donor
      for end-stage renal disease (ESRD) secondary to polycystic kidney disease.His
      immediate posttransplant course was complicated by delayed graft function from
      acute tubular necrosis, reexploration for perigraft hematoma and subsequent wound
      dehiscence. After unsuccessful conservative wound care, the renal allograft
      became completely eviscerated due to fascial retraction of the dehisced wound.
      While the allograft was initially covered with a pedicled rectus femoris muscle
      flap, several local tissue rearrangements were required for definitive coverage.
      The allograft function was recovered after initial flap coverage and was
      subsequently maintained; follow-up more than 2 years after transplantation has
      demonstrated not only continued stable graft function but also complete healing
      of the dehiscent wound.

PMID- 18325081
TI  - Two-stage group sequential robust tests in family-based association studies:
      controlling type I error.
AB  - In family-based association studies, an optimal test statistic with asymptotic
      normal distribution is available when the underlying genetic model is known
      (e.g., recessive, additive, multiplicative, or dominant). In practice, however,
      genetic models for many complex diseases are usually unknown. Using a single test
      statistic optimal for one genetic model may lose substantial power when the model
      is mis-specified. When a family of genetic models is scientifically plausible,
      the maximum of several tests, each optimal for a specific genetic model, is
      robust against the model mis-specification. This robust test is preferred over a
      single optimal test. Recently, cost-effective group sequential approaches have
      been introduced to genetic studies. The group sequential approach allows interim
      analyses and has been applied to many test statistics, but not to the maximum
      statistic. When the group sequential method is applied, type I error should be
      controlled. We propose and compare several approaches of controlling type I error
      rates when group sequential analysis is conducted with the maximum test for
      family-based candidate-gene association studies. For a two-stage group sequential
      robust procedure with a single interim analysis, two critical values for the
      maximum tests are provided based on a given alpha spending function to control
      the desired overall type I error.

PMID- 18325082
TI  - Update and analysis of the University College London low density lipoprotein
      receptor familial hypercholesterolemia database.
AB  - Familial hypercholesterolemia (FH) (OMIM 143890) is most commonly caused by
      variations in the LDLR gene which encodes the receptor for Low Density
      Lipoprotein (LDL) cholesterol particles. We have updated the University College
      London (UCL) LDLR FH database (http://www.ucl.ac.uk/ldlr) by adding variants
      reported in the literature since 2001, converting existing entries to standard
      nomenclature, and transferring the database to the Leiden Open Source Variation
      Database (LOVD) platform. As of July 2007 the database listed 1066 unique LDLR
      gene events. Sixty five percent (n = 689) of the variants are DNA substitutions,
      24% (n = 260) small DNA rearrangements (<100bp) and 11% (n = 117) large DNA
      rearrangements (>100bp), proportions which are similar to those reported in the
      2001 database (n = 683, 62%, 24% and 14% respectively). The DNA substitutions and
      small rearrangements occur along the length of the gene, with 24 in the promoter
      region, 86 in intronic sequences and 839 in the exons (93 nonsense variants, 499
      missense variants and 247 small rearrangements). These occur in all exons, with
      the highest proportion (20%) in exon 4 (186/949); this exon is the largest and
      codes for the critical ligand binding region, where any missense variant is
      likely to be pathogenic. Using the PolyPhen and SIFT prediction computer
      programmes 87% of the missense variants are predicted to have a deleterious
      effect on LDLR activity, and it is probable that at least 48% of the remainder
      are also pathogenic, but their role in FH causation requires confirmation by in
      vitro or family studies.

PMID- 18325083
TI  - Psychometric properties of the Greek version of the NEI-VFQ 25.
AB  - BACKGROUND: To evaluate the reliability and construct validity of a Greek version
      of the NEI-VFQ-25 in patients with chronic ophthalmic diseases. METHODS: We
      developed the Greek version of the instrument using forward and backward
      translation. One hundred-eighty-six patients responded to the questionnaire. To
      examine reliability, Cronbach's alpha for each subscale was used as an index of
      internal consistency. Test-retest reliability was evaluated with intraclass
      correlation coefficients. Regarding construct validity, both convergent and
      discriminant validities were calculated by means of multi-trait analysis. Rasch
      analysis was used to estimate the visual ability required by each item for a
      particular response, and each patient's visual ability. Correspondingly,
      instrument validity was evaluated by estimating the distribution of residuals for
      item and subject measures. RESULTS: Four patient groups were studied, each
      including participants with a single cause of visual impairment. Group 1
      consisted of 84 glaucoma subjects. Group 2 included 30 subjects with age-related
      macular degeneration (ARMD); group 3 included 25 subjects with dry-eye syndrome,
      whereas group 4 included 18 cataract patients. Twenty-nine healthy individuals
      comprised the control group. NEI-VFQ scores (mean +/- SD) for the glaucoma, ARMD,
      dry-eye, cataract and control groups were: 76.9 +/- 20.2, 70.9 +/- 20.2, 81.6 +/-
      16.5, 73.5 +/- 24.0 and 93.7 +/- 8.9 respectively. Item analysis revealed no
      significant data skewing. Cronbach's alpha ranged from 0.678 to 0.926, with most
      subscales having high internal consistency. Intraclass correlation coefficient
      ranged from 0.717 to 0.910 for all subscales. All items passed the convergent and
      discriminant validity tests. Strong correlations were detected between visual
      acuity and "general vision", "distant activities" and "near activities"
      subscales. Significant correlations were also detected between visual field
      deficits and the "peripheral vision" and "general vision" subscales. Rasch
      analysis revealed potential weaknesses of the instrument that are associated with
      the assumptions of the model itself. Specifically, low precision of the
      "agreement" items was detected in the estimation of visual ability. Twenty-three
      percent of the subjects had fit statistics that fell outside the tolerance box.
      CONCLUSION: Although traditional validation methods indicated that the Greek
      version of the NEI-VFQ-25 is a valid and reliable instrument for VS-QoL
      assessment, Rasch analysis detected significant misfits to the model, especially
      of the "agreement" items. This means that results of the corresponding subscales
      should be interpreted with extreme caution.

PMID- 18325084
TI  - Comparison of different real-time PCR chemistries and their suitability for
      detection and quantification of genetically modified organisms.
AB  - BACKGROUND: The real-time polymerase chain reaction is currently the method of
      choice for quantifying nucleic acids in different DNA based quantification
      applications. It is widely used also for detecting and quantifying genetically
      modified components in food and feed, predominantly employing TaqMan and SYBR
      Green real-time PCR chemistries. In our study four alternative chemistries: Lux,
      Plexor, Cycling Probe Technology and LNA were extensively evaluated and compared
      using TaqMan chemistry as a reference system. RESULTS: Amplicons were designed on
      the maize invertase gene and the 5'-junction of inserted transgene and plant
      genomic DNA in MON 810 event. Real-time assays were subsequently compared for
      their efficiency in PCR amplification, limits of detection and quantification,
      repeatability and accuracy to test the performance of the assays. Additionally,
      the specificity of established assays was checked on various transgenic and non
      transgenic plant species. The overall applicability of the designed assays was
      evaluated, adding practicability and costs issues to the performance
      characteristics. CONCLUSION: Although none of the chemistries significantly
      outperformed the others, there are certain characteristics that suggest that LNA
      technology is an alternative to TaqMan when designing assays for quantitative
      analysis. Because LNA probes are much shorter they might be especially
      appropriate when high specificity is required and where the design of a common
      TaqMan probe is difficult or even impossible due to sequence characteristics.
      Plexor on the other hand might be a method of choice for qualitative analysis
      when sensitivity, low cost and simplicity of use prevail.

PMID- 18325085
TI  - Biomonitoring of complex occupational exposures to carcinogens: the case of
      sewage workers in Paris.
AB  - BACKGROUND: Sewage workers provide an essential service in the protection of
      public and environmental health. However, they are exposed to varied mixtures of
      chemicals; some are known or suspected to be genotoxics or carcinogens. Thus,
      trying to relate adverse outcomes to single toxicant is inappropriate. We aim to
      investigate if sewage workers are at increased carcinogenic risk as evaluated by
      biomarkers of exposure and early biological effects. METHODS/DESIGN: This cross
      sectional study will compare exposed sewage workers to non-exposed office
      workers. Both are voluntaries from Paris municipality, males, aged (20-60) years,
      non-smokers since at least six months, with no history of chronic or recent
      illness, and have similar socioeconomic status. After at least 3 days of
      consecutive work, blood sample and a 24-hour urine will be collected. A caffeine
      test will be performed, by administering coffee and collecting urines three hours
      after. Subjects will fill in self-administered questionnaires; one covering the
      professional and lifestyle habits while the a second one is alimentary. The blood
      sample will be used to assess DNA adducts in peripheral lymphocytes. The 24-hour
      urine to assess urinary 8-oxo-7, 8-dihydro-2'-deoxy-Guanosine (8-oxo-dG), and the
      in vitro genotoxicity tests (comet and micronucleus) using HeLa S3 or HepG2
      cells. In parallel, occupational air sampling will be conducted for some
      Polycyclic Aromatic Hydrocarbons and Volatile Organic Compounds. A weekly
      sampling chronology at the offices of occupational medicine in Paris city during
      the regular medical visits will be followed. This protocol has been accepted by
      the French Est III Ethical Comitee with the number 2007-A00685-48. DISCUSSION:
      Biomarkers of exposure and of early biological effects may help overcome the
      limitations of environmental exposure assessment in very complex occupational or
      environmental settings.

PMID- 18325086
TI  - Selective masking and demasking for the stepwise complexometric determination of
      aluminium, lead and zinc from the same solution.
AB  - BACKGROUND: A complexometric method based on selective masking and de-masking has
      been developed for the rapid determination of aluminium, lead and zinc from the
      same solution in glass and glass frit samples. The determination is carried out
      using potassium cyanide to mask zinc, and excess disodium salt of EDTA to mask
      lead and aluminium. The excess EDTA was titrated with standard Mn(II)SO(4
      )solution using Erichrome Black-T as the indicator. Subsequently selective de
      masking agents - triethanolamine, 2,3-dimercaptopropanol and a
      formaldehyde/acetone mixture - were used to determine quantities of aluminium,
      lead and zinc in a stepwise and selective manner. RESULTS: The accuracy of the
      method was established by analysing glass certified reference material NBS 1412.
      The standard deviation of the measurements, calculated by analysing five
      replicates of each sample, was found to be less than 1.5% for the method
      proposed. CONCLUSION: The novelty of the method lies in its simplicity and
      accuracy afforded by there not being a need for a prior separation or
      instrumentation. The proposed method was found to be highly selective for the
      precise determination of aluminum, zinc and lead in the routine analysis of glass
      batch and allied materials.

PMID- 18325087
TI  - Cardiovascular disease in patients with rheumatoid arthritis: results from the
      QUEST-RA study.
AB  - INTRODUCTION: We analyzed the prevalence of cardiovascular (CV) disease in
      patients with rheumatoid arthritis (RA) and its association with traditional CV
      risk factors, clinical features of RA, and the use of disease-modifying
      antirheumatic drugs (DMARDs) in a multinational cross-sectional cohort of
      nonselected consecutive outpatients with RA (The Questionnaires in Standard
      Monitoring of Patients with Rheumatoid Arthritis Program, or QUEST-RA) who were
      receiving regular clinical care. METHODS: The study involved a clinical
      assessment by a rheumatologist and a self-report questionnaire by patients. The
      clinical assessment included a review of clinical features of RA and exposure to
      DMARDs over the course of RA. Comorbidities were recorded; CV morbidity included
      myocardial infarction, angina, coronary disease, coronary bypass surgery, and
      stroke. Traditional risk factors recorded were hypertension, hyperlipidemia,
      diabetes mellitus, smoking, physical inactivity, and body mass index. Unadjusted
      and adjusted hazard ratios (HRs) (95% confidence interval [CI]) for CV morbidity
      were calculated using Cox proportional hazard regression models. RESULTS: Between
      January 2005 and October 2006, the QUEST-RA project included 4,363 patients from
      48 sites in 15 countries; 78% were female, more than 90% were Caucasian, and the
      mean age was 57 years. The prevalence for lifetime CV events in the entire sample
      was 3.2% for myocardial infarction, 1.9% for stroke, and 9.3% for any CV event.
      The prevalence for CV risk factors was 32% for hypertension, 14% for
      hyperlipidemia, 8% for diabetes, 43% for ever-smoking, 73% for physical
      inactivity, and 18% for obesity. Traditional risk factors except obesity and
      physical inactivity were significantly associated with CV morbidity. There was an
      association between any CV event and age and male gender and between extra
      articular disease and myocardial infarction. Prolonged exposure to methotrexate
      (HR 0.85; 95% CI 0.81 to 0.89), leflunomide (HR 0.59; 95% CI 0.43 to 0.79),
      sulfasalazine (HR 0.92; 95% CI 0.87 to 0.98), glucocorticoids (HR 0.95; 95% CI
      0.92 to 0.98), and biologic agents (HR 0.42; 95% CI 0.21 to 0.81; P < 0.05) was
      associated with a reduction of the risk of CV morbidity; analyses were adjusted
      for traditional risk factors and countries. CONCLUSION: In conclusion, prolonged
      use of treatments such as methotrexate, sulfasalazine, leflunomide,
      glucocorticoids, and tumor necrosis factor-alpha blockers appears to be
      associated with a reduced risk of CV disease. In addition to traditional risk
      factors, extra-articular disease was associated with the occurrence of myocardial
      infarction in patients with RA.

PMID- 18325088
TI  - Optimization of treatment with interferon beta in multiple sclerosis. Usefulness
      of automatic system application criteria.
AB  - BACKGROUND: A software based tool has been developed (Optem) to allow automatize
      the recommendations of the Canadian Multiple Sclerosis Working Group for
      optimizing MS treatment in order to avoid subjective interpretation. METHODS:
      Treatment Optimization Recommendations (TORs) were applied to our database of
      patients treated with IFN beta1a IM. Patient data were assessed during year 1 for
      disease activity, and patients were assigned to 2 groups according to TOR:
      "change treatment" (CH) and "no change treatment" (NCH). These assessments were
      then compared to observed clinical outcomes for disease activity over the
      following years. RESULTS: We have data on 55 patients. The "change treatment"
      status was assigned to 22 patients, and "no change treatment" to 33 patients. The
      estimated sensitivity and specificity according to last visit status were 73.9%
      and 84.4%. During the following years, the Relapse Rate was always higher in the
      "change treatment" group than in the "no change treatment" group (5 y; CH: 0.7,
      NCH: 0.07; p < 0.001, 12 m - last visit; CH: 0.536, NCH: 0.34). We obtained the
      same results with the EDSS (4 y; CH: 3.53, NCH: 2.55, annual progression rate in
      12 m - last visit; CH: 0.29, NCH: 0.13). CONCLUSION: Applying TOR at the first
      year of therapy allowed accurate prediction of continued disease activity in
      relapses and disability progression.

PMID- 18325089
TI  - Ability of pleth variability index to detect hemodynamic changes induced by
      passive leg raising in spontaneously breathing volunteers.
AB  - INTRODUCTION: Pleth Variability Index (PVI) is a new algorithm that allows
      continuous and automatic estimation of respiratory variations in the pulse
      oximeter waveform amplitude. Our aim was to test its ability to detect changes in
      preload induced by passive leg raising (PLR) in spontaneously breathing
      volunteers. METHODS: We conducted a prospective observational study. Twenty-five
      spontaneously breathing volunteers were enrolled. PVI, heart rate and noninvasive
      arterial pressure were recorded. Cardiac output was assessed using transthoracic
      echocardiography. Volunteers were studied in three successive positions: baseline
      (semirecumbent position); after PLR of 45 degrees with the trunk lowered in the
      supine position; and back in the semirecubent position. RESULTS: We observed
      significant changes in cardiac output and PVI during changes in body position. In
      particular, PVI decreased significantly from baseline to PLR (from 21.5 +/- 8.0%
      to 18.3 +/- 9.4%; P < 0.05) and increased significantly from PLR to the
      semirecumbent position (from 18.3 +/- 9.4% to 25.4 +/- 10.6 %; P < 0.05). A
      threshold PVI value above 19% was a weak but significant predictor of response to
      PLR (sensitivity 82%, specificity 57%, area under the receiver operating
      characteristic curve 0.734 +/- 0.101). CONCLUSION: PVI can detect haemodynamic
      changes induced by PLR in spontaneously breathing volunteers. However, we found
      that PVI was a weak predictor of fluid responsiveness in this setting.

PMID- 18325090
TI  - Detecting the molecular scars of evolution in the Mycobacterium tuberculosis
      complex by analyzing interrupted coding sequences.
AB  - BACKGROUND: Computer-assisted analyses have shown that all bacterial genomes
      contain a small percentage of open reading frames with a frameshift or in-frame
      stop codon We report here a comparative analysis of these interrupted coding
      sequences (ICDSs) in six isolates of M. tuberculosis, two of M. bovis and one of
      M. africanum and question their phenotypic impact and evolutionary significance.
      RESULTS: ICDSs were classified as "common to all strains" or "strain-specific".
      Common ICDSs are believed to result from mutations acquired before the divergence
      of the species, whereas strain-specific ICDSs were acquired after this
      divergence. Comparative analyses of these ICDSs therefore define the molecular
      signature of a particular strain, phylogenetic lineage or species, which may be
      useful for inferring phenotypic traits such as virulence and molecular
      relationships. For instance, in silico analysis of the W-Beijing lineage of M.
      tuberculosis, an emergent family involved in several outbreaks, is readily
      distinguishable from other phyla by its smaller number of common ICDSs, including
      at least one known to be associated with virulence. Our observation was confirmed
      through the sequencing analysis of ICDSs in a panel of 21 clinical M.
      tuberculosis strains. This analysis further illustrates the divergence of the W
      Beijing lineage from other phyla in terms of the number of full-length ORFs not
      containing a frameshift. We further show that ICDS formation is not associated
      with the presence of a mutated promoter, and suggest that promoter extinction is
      not the main cause of pseudogene formation. CONCLUSION: The correlation between
      ICDSs, function and phenotypes could have important evolutionary implications.
      This study provides population geneticists with a list of targets, which could
      undergo selective pressure and thus alters relationships between the various
      lineages of M. tuberculosis strains and their host. This approach could be
      applied to any closely related bacterial strains or species for which several
      genome sequences are available.

PMID- 18325091
TI  - Long-term follow-up on the use of vascularized fibular graft for the treatment of
      congenital pseudarthrosis of the tibia.
AB  - BACKGROUND: Congenital pseudoarthrosis of the tibia (CPT) is one of the most
      difficult conditions to treat. METHODS: Five girls and 3 boys with CPT were
      treated by vascularized fibular grafting (VFG). The average age at VFG was 7.0
      years (range: 1.9-11.5 years) with an average follow-up term of 11.7 years
      (range: 4.9-19.6 years). Five of the children had undergone multiple operations
      before VFG, while the other 3 had no such history. RESULTS: Bone consolidation
      was obtained in all cases after an average term of 6.6 months (range: 4-10
      months); this was with the first VFG in 7 cases but with the second VFG in 1
      case. Complication of stress fracture and ankle pain occurred in 1 and 3 cases,
      respectively, only in cases undergoing multiple operations. Leg-length
      discrepancy was more prominent in the patients with multiple previous operations
      (mean: 7.5 cm), than in the cases with no prior surgery (mean: 0.7 cm).
      CONCLUSION: The long-term results of VFG for CPT were excellent, especially in
      the cases, with no prior surgery. VFG should be considered as a primary treatment
      option for CPT.

PMID- 18325092
TI  - The histopathology of septic acute kidney injury: a systematic review.
AB  - INTRODUCTION: Sepsis is the most common trigger of acute kidney injury (AKI) in
      critically ill patients; understanding the structural changes associated with its
      occurrence is therefore important. Accordingly, we systematically reviewed the
      literature to assess current knowledge on the histopathology of septic AKI.
      METHODS: A systematic review of the MEDLINE, EMBASE and CINHAL databases and
      bibliographies of the retrieved articles was performed for all studies describing
      kidney histopathology in septic AKI. RESULTS: We found six studies reporting the
      histopathology of septic AKI for a total of only 184 patients. Among these
      patients, only 26 (22%) had features suggestive of acute tubular necrosis (ATN).
      We found four primate studies. In these, seven out of 19 (37%) cases showed
      features of ATN. We also found 13 rodent studies of septic AKI. In total, 23%
      showed evidence of ATN. In two additional studies performed in a dog model and a
      sheep model there was no evidence of ATN on histopathologic examination. Overall,
      when ATN was absent, studies reported a wide variety of kidney morphologic
      changes in septic AKI - ranging from normal (in most cases) to marked cortical
      tubular necrosis. CONCLUSION: There are no consistent renal histopathological
      changes in human or experimental septic AKI. The majority of studies reported
      normal histology or only mild, nonspecific changes. ATN was relatively uncommon.

PMID- 18325093
TI  - Hospital Anxiety and Depression Scale (HADS): validation in a Greek general
      hospital sample.
AB  - BACKGROUND: The Hospital Anxiety and Depression Scale (HADS) has been used in
      several languages to assess anxiety and depression in general hospital patients
      with good results. METHODS: The HADS was administered to 521 participants (275
      controls and 246 inpatients and outpatients of the Internal Medicine and Surgical
      Departments in 'Attikon' General Hospital in Athens). The Beck Depression
      Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) were used as 'gold
      standards' for depression and anxiety respectively. RESULTS: The HADS presented
      high internal consistency; Cronbach's alpha coefficient was 0.884 (0.829 for
      anxiety and 0.840 for depression) and stability (test-retest intraclass
      correlation coefficient 0.944). Factor analysis showed a two-factor structure.
      The HADS showed high concurrent validity; the correlations of the scale and its
      subscales with the BDI and the STAI were high (0.722 - 0.749). CONCLUSION: The
      Greek version of HADS showed good psychometric properties and could serve as a
      useful tool for clinicians to assess anxiety and depression in general hospital
      patients.

PMID- 18325094
TI  - Lymphangiogenesis and lymph node metastasis in breast cancer.
AB  - INTRODUCTION: There have been few studies on lymphangiogenesis in the past due to
      the lack of specific lymphatic endothelial markers, and lymphatic-specific growth
      factors. Recently, these limitations have been relieved by the discovery of a
      small number of potential lymphatic-specific markers. The relationship between
      lymphangiogenesis and regional or distant metastasis has not previously been
      investigated in humans. Using these lymphatic markers, it is possible to explore
      the relationship between lymphangiogenesis and tumour metastasis. This study
      indirectly quantified lymphangiogenesis by measuring mRNA expression of all seven
      lymphatic markers described above in breast cancers and correlated these markers
      with lymphatic involvement and survival. The cDNA from 153 frozen archived breast
      samples were analysed with Q-PCR for all seven lymphangiogenic markers. This was
      correlated with various prognostic factors as well as patient survival. RESULTS:
      There was significantly greater expression of all 7 markers in malignant compared
      to benign breast tissue. In addition, there was greater expression in lymph node
      positive/grade 3 tumours when compared to lymph node negative/grade 1 tumours. In
      5 of the markers, there was a greater expression in poor NPI prognostic tumours
      when compared to favourable prognostic tumours which was not statistically
      significant. There was no association between recurrence risk and lymphangiogenic
      marker expression. CONCLUSION: In summary, the findings from this study show that
      lymphangiogenesis, measured by specific lymphatic marker expression, is higher in
      breast cancers than in normal breast tissue. Secondly, breast cancers which have
      metastasised to the regional lymphatics show higher expression compared to those
      which have not, although the individual differences for all five markers were not
      statistically significant.

PMID- 18325095
TI  - Pyoderma gangrenosum after totally implanted central venous access device
      insertion.
AB  - BACKGROUND: Pyoderma gangrenosum is an aseptic skin disease. The ulcerative form
      of pyoderma gangrenosum is characterized by a rapidly progressing painful
      irregular and undermined bordered necrotic ulcer. The aetiology of pyoderma
      gangrenosum remains unclear. In about 70% of cases, it is associated with a
      systemic disorder, most often inflammatory bowel disease, haematological disease
      or arthritis. In 25-50% of cases, a triggering factor such as recent surgery or
      trauma is identified. Treatment consists of local and systemic approaches.
      Systemic steroids are generally used first. If the lesions are refractory,
      steroids are combined with other immunosuppressive therapy or to antimicrobial
      agents. CASE PRESENTATION: A 90 years old patient with myelodysplastic syndrome,
      seeking regular transfusions required totally implanted central venous access
      device (Port-a-Cath(R)) insertion. Fever and inflammatory skin reaction at the
      site of insertion developed on the seventh post-operative day, requiring the
      device's explanation. A rapid progression of the skin lesions evolved into a
      circular skin necrosis. Intravenous steroid treatment stopped the necrosis'
      progression. CONCLUSION: Early diagnosis remains the most important step to the
      successful treatment of pyoderma gangrenosum.

PMID- 18325096
TI  - Cracked mercury dental amalgam as a possible cause of fever of unknown origin: a
      case report.
AB  - INTRODUCTION: Sudden fever of unknown origin is quite a common emergency and may
      lead to hospitalization. A rise in body temperature can be caused by infectious
      diseases and by other types of medical condition. This case report is of a woman
      who had fever at night for several days and other clinical signs which were
      likely related to cracked dental mercury amalgam. CASE PRESENTATION: A healthy
      women developed fever many days after had cracked a mercury dental amalgam
      filling. Blood tests evidenced increased erythrocyte sedimentation rate, anemia
      and elevated white cell count; symptoms were headache and palpitations. Blood
      tests and symptoms normalized within three weeks of removal of the dental
      amalgam. CONCLUSION: This case highlights the possible link between mercury vapor
      exposure from cracked dental amalgam and early activation of the immune system
      leading to fever of unknown origin.

PMID- 18325097
TI  - Non-Hodgkin's lymphoma in a woman with adult-onset Still's disease: a case
      report.
AB  - INTRODUCTION: Adult onset Still's disease is a chronic multisystemic inflammatory
      disorder characterized by high spiking fever, polyarthralgia and rash.
      Lymphadenopathy is a prominent feature of adult onset Still's disease and is seen
      in about 65% of patients. Searching the medical literature using the MEDLINE
      database from January 1966 through November 2007 we could only find two reported
      cases of adult onset Still's disease that had progressed to lymphoma. CASE
      PRESENTATION: We describe a woman who was diagnosed with adult onset Still's
      disease and developed lymphoma 10 months after the onset of her symptoms. She
      initially presented with fever and arthritis of the knees, ankles and shoulders,
      along with a nonpruritic skin rash, myalgia and weight loss. On physical
      examination she was found to have several enlarged anterior cervical lymph nodes
      and left posterior auricular lymph nodes all of which were non-tender, immobile
      and rubbery. Excisional biopsy of the cervical lymph nodes was negative for
      malignancy. Bone marrow biopsy was also negative for malignancy. She was treated
      with prednisone. She remained in good health until she presented 10 months later
      with low back pain, dyspnea and weight loss. Work up revealed malignant lymphoma.
      She was treated with chemotherapy and was doing well until she presented with
      abdominal pain. Work up revealed a cirrhotic liver and ascites. She then passed
      away from hepatorenal syndrome 13 years after the diagnosis of lymphoma. To our
      knowledge, this is the third reported case of such an occurrence. CONCLUSION:
      Although the association between adult onset Still's disease and lymphoma has
      been rarely reported, careful screening for this malignancy in patients suspected
      to have adult onset Still's disease is warranted.

PMID- 18325098
TI  - Selection of housekeeping genes for gene expression studies in larvae from
      flatfish using real-time PCR.
AB  - BACKGROUND: Flatfish metamorphosis involves major physiological and morphological
      changes. Due to its importance in aquaculture and as a model for developmental
      studies, some gene expression studies have focused on the understanding of this
      process using quantitative real-time PCR (qRT-PCR) technique. Therefore, adequate
      reference genes for accurate normalization are required. RESULTS: The stability
      of 12 potential reference genes was examined during larval development in
      Senegalese sole (Solea senegalensis) and Atlantic halibut (Hippoglossus
      hippoglossus) to determine the most suitable genes for qRT-PCR analysis.
      Transcription levels of genes encoding beta-Actin (ACTB), glyceraldehyde-3P
      dehydrogenase (GAPDH), annexin A2 (ANXA2), glutathione S-transferase (GST),
      ornithine decarboxylase (ODC), hypoxanthine phosphoribosyltransferase (HPRT1),
      ubiquitin (UBQ), elongation factor 1 alpha (eEF1A1), 18S ribosomal RNA, and the
      ribosomal proteins S4 (RPS4) and L13a (RPL13a) were quantitated. Two paralogous
      genes for ACTB were analyzed in each of both flatfish species. In addition, two
      paralogous genes for GAPDH were studied in Senegalese sole. RPL13a represented
      non-orthologous genes between both flatfish species. GeNorm and NormFinder
      analyses for expression stability revealed RPS4, UBQ and eEF1A1 as the most
      stable genes in Senegalese sole, Atlantic halibut and in a combined analysis. In
      all cases, paralogous genes exhibited differences in expression stability.
      CONCLUSION: This work suggests RPS4, UBQ, and eEF1A1 genes as useful reference
      genes for accurate normalization in qRT-PCR studies in Senegalese sole and
      Atlantic halibut larvae. The congruent results between both species in spite of
      the drastic differences in larval development suggest that selected housekeeping
      genes (HKGs) could be useful in other flatfish species. However, the finding of
      paralogous gene copies differentially expressed during development in some HKGs
      underscores the necessity to identify orthologous genes.

PMID- 18325099
TI  - Uterine PEComa: appraisal of a controversial and increasingly reported
      mesenchymal neoplasm.
AB  - In recent years, a group of tumors that have been designated "perivascular
      epithelioid cell tumors" (PEComa) have been reported with increasing frequency
      from a wide variety of anatomic locations. The uterus and retroperitoneum appear
      to be the most frequent sites of origin for these lesions. PEComas belong to an
      identically named family of tumors comprised of conventional angiomyolipomas,
      clear cell sugar tumors, lymphangiomyomatosis and clear cell myomelanocytic tumor
      of the falciform ligament/ligament teres, and are also known as PEComa-NOS. This
      article is a primer for clinicians on the most salient clinicopathologic features
      of uterine PEComas, as most of the debate and discussion have taken place in the
      pathologic literature. The author appraises in detail the current state of
      knowledge on PEComas of the uterus based on a review of published data on the 44
      previously reported cases, and comments on areas of controversy. The latter are
      centered predominantly on the significant morphologic and immunophenotypic
      overlap that exists between uterine PEComa and some smooth muscle tumors of the
      uterus. The clinicopathologic features of cases reported as epithelioid smooth
      muscle tumors and cases reported as uterine PEComas are compared and contrasted,
      and a practical approach to their reporting is proposed.

PMID- 18325100
TI  - Ranking analysis of F-statistics for microarray data.
AB  - BACKGROUND: Microarray technology provides an efficient means for globally
      exploring physiological processes governed by the coordinated expression of
      multiple genes. However, identification of genes differentially expressed in
      microarray experiments is challenging because of their potentially high type I
      error rate. Methods for large-scale statistical analyses have been developed but
      most of them are applicable to two-sample or two-condition data. RESULTS: We
      developed a large-scale multiple-group F-test based method, named ranking
      analysis of F-statistics (RAF), which is an extension of ranking analysis of
      microarray data (RAM) for two-sample t-test. In this method, we proposed a novel
      random splitting approach to generate the null distribution instead of using
      permutation, which may not be appropriate for microarray data. We also
      implemented a two-simulation strategy to estimate the false discovery rate.
      Simulation results suggested that it has higher efficiency in finding
      differentially expressed genes among multiple classes at a lower false discovery
      rate than some commonly used methods. By applying our method to the experimental
      data, we found 107 genes having significantly differential expressions among 4
      treatments at <0.7% FDR, of which 31 belong to the expressed sequence tags
      (ESTs), 76 are unique genes who have known functions in the brain or central
      nervous system and belong to six major functional groups. CONCLUSION: Our method
      is suitable to identify differentially expressed genes among multiple groups, in
      particular, when sample size is small.

PMID- 18325101
TI  - Phenylbutyrate interferes with the Fanconi anemia and BRCA pathway and sensitizes
      head and neck cancer cells to cisplatin.
AB  - BACKGROUND: Cisplatin has been widely used to treat head and neck cancer. One of
      the clinical limitations with this treatment, however, is that tumors that are
      initially responsive to cisplatin later acquire resistance. We have recently
      shown that a subset of head and neck cancer cell lines has a defective Fanconi
      anemia DNA damage response pathway and this defect correlates to cisplatin
      sensitivity. We have also shown that the histone deacetylase inhibitor
      phenylbutyrate sensitize human cells to cisplatin. In this study we explored
      whether phenylbutyrate may sensitize head and neck cancer cells by interfering
      with the Fanconi anemia pathway. RESULTS: We found that the phenylbutyrate
      sensitizes head and neck cancer cell lines to cisplatin. This sensitization by
      phenylbutyrate correlated to a significant decrease in the formation of cisplatin
      induced FANCD2 nuclear foci, which is a functional read out of the Fanconi anemia
      and BRCA (FA/BRCA) pathway. This abrogation of the FA/BRCA pathway by
      phenylbutyrate was not due to loss of FANCD2 monoubiquitylation but rather
      correlated to a phenylbutyrate-mediated reduction in the expression of the BRCA1
      protein. Furthermore, we found that cancer cells defective in the FA pathway were
      also sensitized to cisplatin by phenylbutyrate suggesting that phenylbutyrate
      targets additional pathways. CONCLUSION: The results from this study suggest that
      phenylbutyrate may have therapeutic utility as a cisplatin sensitizer in head and
      neck cancer by inhibiting the FA/BRCA pathway through the down regulation of
      BRCA1 as well as by an FA/BRCA-independent mechanism.

PMID- 18325102
TI  - A web-based Alcohol Clinical Training (ACT) curriculum: is in-person faculty
      development necessary to affect teaching?
AB  - BACKGROUND: Physicians receive little education about unhealthy alcohol use and
      as a result patients often do not receive efficacious interventions. The
      objective of this study is to evaluate whether a free web-based alcohol
      curriculum would be used by physician educators and whether in-person faculty
      development would increase its use, confidence in teaching and teaching itself.
      METHODS: Subjects were physician educators who applied to attend a workshop on
      the use of a web-based curriculum about alcohol screening and brief intervention
      and cross-cultural efficacy. All physicians were provided the curriculum web
      address. Intervention subjects attended a 3-hour workshop including demonstration
      of the website, modeling of teaching, and development of a plan for using the
      curriculum. All subjects completed a survey prior to and 3 months after the
      workshop. RESULTS: Of 20 intervention and 13 control subjects, 19 (95%) and 10
      (77%), respectively, completed follow-up. Compared to controls, intervention
      subjects had greater increases in confidence in teaching alcohol screening, and
      in the frequency of two teaching practices - teaching about screening and
      eliciting patient health beliefs. Teaching confidence and teaching practices
      improved significantly in 9 of 10 comparisons for intervention, and in 0
      comparisons for control subjects. At follow-up 79% of intervention but only 50%
      of control subjects reported using any part of the curriculum (p = 0.20).
      CONCLUSION: In-person training for physician educators on the use of a web-based
      alcohol curriculum can increase teaching confidence and practices. Although the
      web is frequently used for dissemination, in-person training may be preferable to
      effect widespread teaching of clinical skills like alcohol screening and brief
      intervention.

PMID- 18325103
TI  - CDKN1C/p57kip2 is a candidate tumor suppressor gene in human breast cancer.
AB  - BACKGROUND: CDKN1C (also known as p57KIP2) is a cyclin-dependent kinase inhibitor
      previously implicated in several types of human cancer. Its family members
      (CDKN1A/p21CIP1 and B/p27KIP1) have been implicated in breast cancer, but
      information about CDKN1C's role is limited. We hypothesized that decreased CDKN1C
      may be involved in human breast carcinogenesis in vivo. METHODS: We determined
      rates of allele imbalance or loss of heterozygosity (AI/LOH) in CDKN1C, using an
      intronic polymorphism, and in the surrounding 11p15.5 region in 82 breast
      cancers. We examined the CDKN1C mRNA level in 10 cancers using quantitative real
      time PCR (qPCR), and the CDKN1C protein level in 20 cancers using
      immunohistochemistry (IHC). All samples were obtained using laser
      microdissection. Data were analyzed using standard statistical tests. RESULTS:
      AI/LOH at 11p15.5 occurred in 28/73 (38%) informative cancers, but CDKN1C itself
      underwent AI/LOH in only 3/16 (19%) cancers (p = ns). In contrast, CDKN1C mRNA
      levels were reduced in 9/10 (90%) cancers (p < 0.0001), ranging from 2-60% of
      paired normal epithelium. Similarly, CDKN1C protein staining was seen in 19/20
      (95%) cases' normal epithelium but in only 7/14 (50%) cases' CIS (p < 0.004) and
      5/18 (28%) cases' IC (p < 0.00003). The reduction appears primarily due to loss
      of CDKN1C expression from myoepithelial layer cells, which stained intensely in
      17/20 (85%) normal lobules, but in 0/14 (0%) CIS (p < 0.00001). In contrast,
      luminal cells displayed less intense, focal staining fairly consistently across
      histologies. Decreased CDKN1C was not clearly associated with tumor grade,
      histology, ER, PR or HER2 status. CONCLUSION: CDKN1C is expressed in normal
      epithelium of most breast cancer cases, mainly in the myothepithelial layer. This
      expression decreases, at both the mRNA and protein level, in the large majority
      of breast cancers, and does not appear to be mediated by AI/LOH at the gene.
      Thus, CDKN1C may be a breast cancer tumor suppressor.

PMID- 18325104
TI  - Discovering gene annotations in biomedical text databases.
AB  - BACKGROUND: Genes and gene products are frequently annotated with Gene Ontology
      concepts based on the evidence provided in genomics articles. Manually locating
      and curating information about a genomic entity from the biomedical literature
      requires vast amounts of human effort. Hence, there is clearly a need
      forautomated computational tools to annotate the genes and gene products with
      Gene Ontology concepts by computationally capturing the related knowledge
      embedded in textual data. RESULTS: In this article, we present an automated
      genomic entity annotation system, GEANN, which extracts information about the
      characteristics of genes and gene products in article abstracts from PubMed, and
      translates the discoveredknowledge into Gene Ontology (GO) concepts, a widely
      used standardized vocabulary of genomic traits. GEANN utilizes textual
      "extraction patterns", and a semantic matching framework to locate phrases
      matching to a pattern and produce Gene Ontology annotations for genes and gene
      products. In our experiments, GEANN has reached to the precision level of 78% at
      therecall level of 61%. On a select set of Gene Ontology concepts, GEANN either
      outperforms or is comparable to two other automated annotation studies. Use of
      WordNet for semantic pattern matching improves the precision and recall by 24%
      and 15%, respectively, and the improvement due to semantic pattern matching
      becomes more apparent as the Gene Ontology terms become more general. CONCLUSION:
      GEANN is useful for two distinct purposes: (i) automating the annotation of
      genomic entities with Gene Ontology concepts, and (ii) providing existing
      annotations with additional "evidence articles" from the literature. The use of
      textual extraction patterns that are constructed based on the existing
      annotations achieve high precision. The semantic pattern matching framework
      provides a more flexible pattern matching scheme with respect to "exactmatching"
      with the advantage of locating approximate pattern occurrences with similar
      semantics. Relatively low recall performance of our pattern-based approach may be
      enhanced either by employing a probabilistic annotation framework based on the
      annotation neighbourhoods in textual data, or, alternatively, the statistical
      enrichment threshold may be adjusted to lower values for applications that put
      more value on achieving higher recall values.

PMID- 18325105
TI  - The molecular evolution of four anti-malarial immune genes in the Anopheles
      gambiae species complex.
AB  - BACKGROUND: If the insect innate immune system is to be used as a potential
      blocking step in transmission of malaria, then it will require targeting one or a
      few genes with highest relevance and ease of manipulation. The problem is to
      identify and manipulate those of most importance to malaria infection without the
      risk of decreasing the mosquito's ability to stave off infections by microbes in
      general. Molecular evolution methodologies and concepts can help identify such
      genes. Within the setting of a comparative molecular population genetic and
      phylogenetic framework, involving six species of the Anopheles gambiae complex,
      we investigated whether a set of four pre-selected immunity genes (gambicin, NOS,
      Rel2 and FBN9) might have evolved under selection pressure imposed by the malaria
      parasite. RESULTS: We document varying levels of polymorphism within and
      divergence between the species, in all four genes. Introgression and the sharing
      of ancestral polymorphisms, two processes that have been documented in the past,
      were verified in this study in all four studied genes. These processes appear to
      affect each gene in different ways and to different degrees. However, there is no
      evidence of positive selection acting on these genes. CONCLUSION: Considering the
      results presented here in concert with previous studies, genes that interact
      directly with the Plasmodium parasite, and play little or no role in defense
      against other microbes, are probably the most likely candidates for a specific
      adaptive response against P. falciparum. Furthermore, since it is hard to
      establish direct evidence linking the adaptation of any candidate gene to P.
      falciparum infection, a comparative framework allowing at least an indirect link
      should be provided. Such a framework could be achieved, if a similar approach
      like the one involved here, was applied to all other anopheline complexes that
      transmit P. falciparum malaria.

PMID- 18325106
TI  - Empirical Bayes analysis of single nucleotide polymorphisms.
AB  - BACKGROUND: An important goal of whole-genome studies concerned with single
      nucleotide polymorphisms (SNPs) is the identification of SNPs associated with a
      covariate of interest such as the case-control status or the type of cancer.
      Since these studies often comprise the genotypes of hundreds of thousands of
      SNPs, methods are required that can cope with the corresponding multiple testing
      problem. For the analysis of gene expression data, approaches such as the
      empirical Bayes analysis of microarrays have been developed particularly for the
      detection of genes associated with the response. However, the empirical Bayes
      analysis of microarrays has only been suggested for binary responses when
      considering expression values, i.e. continuous predictors. RESULTS: In this
      paper, we propose a modification of this empirical Bayes analysis that can be
      used to analyze high-dimensional categorical SNP data. This approach along with a
      generalized version of the original empirical Bayes method are available in the R
      package siggenes version 1.10.0 and later that can be downloaded from
      http://www.bioconductor.org. CONCLUSION: As applications to two subsets of the
      HapMap data show, the empirical Bayes analysis of microarrays cannot only be used
      to analyze continuous gene expression data, but also be applied to categorical
      SNP data, where the response is not restricted to be binary. In association
      studies in which typically several ten to a few hundred SNPs are considered, our
      approach can furthermore be employed to test interactions of SNPs. Moreover, the
      posterior probabilities resulting from the empirical Bayes analysis of
      (prespecified) interactions/genotypes can also be used to quantify the importance
      of these interactions.

PMID- 18325107
TI  - The relationship between previous hamstring injury and the concentric isokinetic
      knee muscle strength of Irish Gaelic footballers.
AB  - BACKGROUND: Hamstring injury is one of the most common injuries affecting gaelic
      footballers, similar to other field sports. Research in other sports on whether
      residual hamstring weakness is present after hamstring injury is inconsistent,
      and no study has examined this factor in irish gaelic footballers. The aim of
      this study was to examine whether significant knee muscle weakness is present in
      male Irish gaelic footballers who have returned to full activity after hamstring
      injury. METHODS: The concentric isokinetic knee flexion and extension strength of
      44 members of a university gaelic football team was assessed at 60, 180 and 300
      degrees per second using a Contrex dynamometer. RESULTS: Fifteen players (34%)
      reported a history of hamstring strain, with 68% of injuries affecting the
      dominant (kicking) limb. The hamstrings were significantly stronger (p < 0.05) on
      the dominant limb in all uninjured subjects. The previously injured limbs had a
      significantly lower (p < 0.05) hamstrings to quadriceps (HQ) strength ratio than
      all other non-injured limbs, but neither their hamstrings nor quadriceps were
      significantly weaker (p > 0.05) using this comparison. The previously
      unilaterally injured hamstrings were significantly weaker (p < 0.05) than
      uninjured limbs however, when matched for dominance. The hamstring to opposite
      hamstring (H:oppH) strength ratio of the previously injured players was also
      found to be significantly lower (p < 0.05) than that of the uninjured players.
      CONCLUSION: Hamstring muscle weakness was observed in male Irish gaelic
      footballers with a history of hamstring injury. This weakness is most evident
      when comparisons are made to multiple control populations, both within and
      between subjects. The increased strength of the dominant limb should be
      considered as a potential confounding variable in future trials. The study design
      does not allow interpretation of whether these changes in strength were present
      before or after injury.

PMID- 18325108
TI  - Transcriptome analysis of grain development in hexaploid wheat.
AB  - BACKGROUND: Hexaploid wheat is one of the most important cereal crops for human
      nutrition. Molecular understanding of the biology of the developing grain will
      assist the improvement of yield and quality traits for different environments.
      High quality transcriptomics is a powerful method to increase this understanding.
      RESULTS: The transcriptome of developing caryopses from hexaploid wheat (Triticum
      aestivum, cv. Hereward) was determined using Affymetrix wheat GeneChip
      oligonucleotide arrays which have probes for 55,052 transcripts. Of these, 14,550
      showed significant differential regulation in the period between 6 and 42 days
      after anthesis (daa). Large changes in transcript abundance were observed which
      were categorised into distinct phases of differentiation (6-10 daa), grain fill
      (12-21 daa) and desiccation/maturation (28-42 daa) and were associated with
      specific tissues and processes. A similar experiment on developing caryopses
      grown with dry and/or hot environmental treatments was also analysed, using the
      profiles established in the first experiment to show that most environmental
      treatment effects on transcription were due to acceleration of development, but
      that a few transcripts were specifically affected. Transcript abundance profiles
      in both experiments for nine selected known and putative wheat transcription
      factors were independently confirmed by real time RT-PCR. These expression
      profiles confirm or extend our knowledge of the roles of the known transcription
      factors and suggest roles for the unknown ones. CONCLUSION: This transcriptome
      data will provide a valuable resource for molecular studies on wheat grain. It
      has been demonstrated how it can be used to distinguish general developmental
      shifts from specific effects of treatments on gene expression and to diagnose the
      probable tissue specificity and role of transcription factors.

PMID- 18325109
TI  - Hue-shifted monomeric variants of Clavularia cyan fluorescent protein:
      identification of the molecular determinants of color and applications in
      fluorescence imaging.
AB  - BACKGROUND: In the 15 years that have passed since the cloning of Aequorea
      victoria green fluorescent protein (avGFP), the expanding set of fluorescent
      protein (FP) variants has become entrenched as an indispensable toolkit for cell
      biology research. One of the latest additions to the toolkit is monomeric teal FP
      (mTFP1), a bright and photostable FP derived from Clavularia cyan FP. To gain
      insight into the molecular basis for the blue-shifted fluorescence emission we
      undertook a mutagenesis-based study of residues in the immediate environment of
      the chromophore. We also employed site-directed and random mutagenesis in
      combination with library screening to create new hues of mTFP1-derived variants
      with wavelength-shifted excitation and emission spectra. RESULTS: Our results
      demonstrate that the protein-chromophore interactions responsible for blue
      shifting the absorbance and emission maxima of mTFP1 operate independently of the
      chromophore structure. This conclusion is supported by the observation that the
      Tyr67Trp and Tyr67His mutants of mTFP1 retain a blue-shifted fluorescence
      emission relative to their avGFP counterparts (that is, Tyr66Trp and Tyr66His).
      Based on previous work with close homologs, His197 and His163 are likely to be
      the residues with the greatest contribution towards blue-shifting the
      fluorescence emission. Indeed we have identified the substitutions His163Met and
      Thr73Ala that abolish or disrupt the interactions of these residues with the
      chromophore. The mTFP1-Thr73Ala/His163Met double mutant has an emission peak that
      is 23 nm red-shifted from that of mTFP1 itself. Directed evolution of this double
      mutant resulted in the development of mWasabi, a new green fluorescing protein
      that offers certain advantages over enhanced avGFP (EGFP). To assess the
      usefulness of mTFP1 and mWasabi in live cell imaging applications, we constructed
      and imaged more than 20 different fusion proteins. CONCLUSION: Based on the
      results of our mutagenesis study, we conclude that the two histidine residues in
      close proximity to the chromophore are approximately equal determinants of the
      blue-shifted fluorescence emission of mTFP1. With respect to live cell imaging
      applications, the mTFP1-derived mWasabi should be particularly useful in two
      color imaging in conjunction with a Sapphire-type variant or as a fluorescence
      resonance energy transfer acceptor with a blue FP donor. In all fusions
      attempted, both mTFP1 and mWasabi give patterns of fluorescent localization
      indistinguishable from that of well-established avGFP variants.

PMID- 18325110
TI  - Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and
      full ribosome shotgun sequencing.
AB  - BACKGROUND: Chronic wound pathogenic biofilms are host-pathogen environments that
      colonize and exist as a cohabitation of many bacterial species. These bacterial
      populations cooperate to promote their own survival and the chronic nature of the
      infection. Few studies have performed extensive surveys of the bacterial
      populations that occur within different types of chronic wound biofilms. The use
      of 3 separate16S-based molecular amplifications followed by pyrosequencing,
      shotgun Sanger sequencing, and denaturing gradient gel electrophoresis were
      utilized to survey the major populations of bacteria that occur in the pathogenic
      biofilms of three types of chronic wound types: diabetic foot ulcers (D), venous
      leg ulcers (V), and pressure ulcers (P). RESULTS: There are specific major
      populations of bacteria that were evident in the biofilms of all chronic wound
      types, including Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter,
      Stenotrophomonas, Finegoldia, and Serratia spp. Each of the wound types reveals
      marked differences in bacterial populations, such as pressure ulcers in which 62%
      of the populations were identified as obligate anaerobes. There were also
      populations of bacteria that were identified but not recognized as wound
      pathogens, such as Abiotrophia para-adiacens and Rhodopseudomonas spp. Results of
      molecular analyses were also compared to those obtained using traditional culture
      based diagnostics. Only in one wound type did culture methods correctly identify
      the primary bacterial population indicating the need for improved diagnostic
      methods. CONCLUSION: If clinicians can gain a better understanding of the wound's
      microbiota, it will give them a greater understanding of the wound's ecology and
      will allow them to better manage healing of the wound improving the prognosis of
      patients. This research highlights the necessity to begin evaluating, studying,
      and treating chronic wound pathogenic biofilms as multi-species entities in order
      to improve the outcomes of patients. This survey will also foster the pioneering
      and development of new molecular diagnostic tools, which can be used to identify
      the community compositions of chronic wound pathogenic biofilms and other medical
      biofilm infections.

PMID- 18325111
TI  - Broad and narrow personality traits as markers of one-time and repeated suicide
      attempts: a population-based study.
AB  - BACKGROUND: Studying personality traits with the potential to differentiate
      between individuals engaging in suicide attempts of different degrees of severity
      could help us to understand the processes underlying the link of personality and
      nonfatal suicidal behaviours and to identify at-risk groups. One approach may be
      to examine whether narrow, i.e., lower-order personality traits may be more
      useful than their underlying, broad personality trait dimensions. METHODS: We
      investigated qualitative and quantitative differences in broad and narrow
      personality traits between one-time and repeated suicide attempters in a
      longitudinal, population-based sample of young French Canadian adults using two
      multivariate regression models. RESULTS: One broad (Compulsivity: OR = 2.0; 95%
      CI 1.2-3.5) and one narrow personality trait (anxiousness: OR = 1.1; 95% CI 1.01
      1.1) differentiated between individuals with histories of repeated and one-time
      suicide attempts. Affective instability [(OR = 1.1; 95% CI 1.04-1.1)] and
      anxiousness [(OR = .92; 95% CI .88-.95)], on the other hand, differentiated
      between nonattempters and one-time suicide attempters. CONCLUSION: Emotional and
      cognitive dysregulation and associated behavioural manifestations may be
      associated with suicide attempts of different severity. While findings associated
      with narrow traits may be easier to interpret and link to existing
      sociobiological theories, larger effect sizes associated with broad traits such
      as Compulsivity may be better suited to objectives with a more clinical focus.

PMID- 18325112
TI  - Can "presumed consent" justify the duty to treat infectious diseases? An
      analysis.
AB  - BACKGROUND: AIDS, SARS, and the recent epidemics of the avian-flu have all served
      to remind us the debate over the limits of the moral duty to care. It is
      important to first consider the question of whether or not the "duty to treat"
      might be subject to contextual constraints. The purpose of this study was to
      investigate the opinions and beliefs held by both physicians and dentists
      regarding the occupational risks of infectious diseases, and to analyze the
      argument that the notion of "presumed consent" on the part of professionals may
      be grounds for supporting the duty to treat. METHODS: For this cross-sectional
      survey, the study population was selected from among physicians and dentists in
      Ankara. All of the 373 participants were given a self-administered questionnaire.
      RESULTS: In total, 79.6% of the participants said that they either had some
      degree of knowledge about the risks when they chose their profession or that they
      learned of the risks later during their education and training. Of the
      participants, 5.2% said that they would not have chosen this profession if they
      had been informed of the risks. It was found that 57% of the participants
      believed that there is a standard level of risk, and 52% of the participants
      stated that certain diseases would exceed the level of acceptable risk unless
      specific protective measures were implemented. CONCLUSION: If we use the presumed
      consent argument to establish the duty of the HCW to provide care, we are
      confronted with problems ranging over the difficulty of choosing a profession
      autonomously, the constant level of uncertainty present in the medical
      profession, the near-impossibility of being able to evaluate retrospectively
      whether every individual was informed, and the seemingly inescapable problem that
      this practice would legitimize, and perhaps even foster, discrimination against
      patients with certain diseases. Our findings suggest that another problem can be
      added to the list: one-fifth of the participants in this study either lacked
      adequate knowledge of the occupational risks when they chose the medical
      profession or were not sufficiently informed of these risks during their faculty
      education and training. Furthermore, in terms of the moral duty to provide care,
      it seems that most HCWs are more concerned about the availability of protective
      measures than about whether they had been informed of a particular risk
      beforehand. For all these reasons, the presumed consent argument is not
      persuasive enough, and cannot be used to justify the duty to provide care. It is
      therefore more useful to emphasize justifications other than presumed consent
      when defining the duty of HCWs to provide care, such as the social contract
      between society and the medical profession and the fact that HCWs have a greater
      ability to provide medical aid.

PMID- 18325113
TI  - Bioinformatics prediction of overlapping frameshifted translation products in
      mammalian transcripts.
AB  - BACKGROUND: Exceptionally, a single nucleotide sequence can be translated in vivo
      in two different frames to yield distinct proteins. In the case of the G-protein
      alpha subunit XL-alpha-s transcript, a frameshifted open reading frame (ORF) in
      exon 1 is translated to yield a structurally distinct protein called Alex, which
      plays a role in platelet aggregation and neurological processes. We carried out a
      novel bioinformatics screen for other possible dual-frame translated sequences,
      based on comparative genomics. RESULTS: Our method searched human, mouse and rat
      transcripts in frames +1 and -1 for ORFs which are unusually well conserved at
      the amino acid level. We name these conserved frameshifted overlapping ORFs
      'matreshkas' to reflect their nested character. Select findings of our analysis
      revealed that the G-protein coupled receptor GPR27 is entirely contained within a
      frame -1 matreshka, thrombopoietin contains a matreshka which spans ~70% of its
      length, platelet glycoprotein IIIa (ITGB3) contains a matreshka with the
      predicted characteristics of a secreted peptide hormone, while the potassium
      channel KCNK12 contains a matreshka spanning >400 amino acids. CONCLUSION:
      Although the in vivo existence of translated matreshkas has not been
      experimentally verified, this genome-wide analysis provides strong evidence that
      substantial overlapping coding sequences exist in a number of human and rodent
      transcripts.

PMID- 18325114
TI  - Exercise and manual auricular acupuncture: a pilot assessor-blind randomised
      controlled trial. (The acupuncture and personalised exercise programme (APEP)
      trial).
AB  - BACKGROUND: Evidence supports the use of exercise for chronic low back pain
      (CLBP); however, adherence is often poor due to ongoing pain. Auricular
      acupuncture is a form of pain relief involving the stimulation of points on the
      outer ear corresponding with specific body parts. It may be a useful adjunct to
      exercise in managing CLBP; however, there is only limited evidence to support its
      use with this patient group. METHODS/DESIGN: This study was designed to test the
      feasibility of an assessor-blind randomised controlled trial which assess the
      effects on clinical outcomes and exercise adherence of adding manual auricular
      acupuncture to a personalised and supervised exercise programme (PEP) for CLBP.
      No sample size calculation has been carried out as this study aims to identify
      CLBP referral rates within the catchment area of the study site. The researchers
      aim to recruit four cohorts of n = 20 participants to facilitate a power analysis
      for a future randomised controlled trial. A computer generated random allocation
      sequence will be prepared centrally and used to allocate participants by cohort
      to one of the following interventions: 1) six weeks of PEP plus manual auricular
      acupuncture; 2) six weeks of PEP alone. Both groups will also complete a further
      six weeks of self-paced exercise with telephone follow-up support. In addition to
      a baseline and exit questionnaire at the beginning and end of the study, the
      following outcomes will be collected at baseline, and after 7, 13 and 25 weeks:
      pain frequency and bothersomeness, back-specific function, objective assessment
      and recall of physical activity, use of analgesia, perceived self-efficacy, fear
      avoidance beliefs, and beliefs about the consequences of back pain. Since this is
      a feasibility study, significance tests will not be presented, and treatment
      effects will be represented by point estimates and confidence intervals. For each
      outcome variable, analysis of covariance will be performed on the data,
      conditioning on the baseline value. DISCUSSION: The results of this study
      investigating the adjuvant effects of auricular acupuncture to exercise in
      managing CLBP will be used to inform the design of a future multi-centre
      randomised controlled trial. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN94142364.

PMID- 18325115
TI  - Tissue factor/FVIIa activates Bcl-2 and prevents doxorubicin-induced apoptosis in
      neuroblastoma cells.
AB  - BACKGROUND: Tissue factor (TF) is a transmembrane protein that acts as a receptor
      for activated coagulation factor VII (FVIIa), initiating the coagulation cascade.
      Recent studies demonstrate that expression of tumor-derived TF also mediates
      intracellular signaling relevant to tumor growth and apoptosis. Our present study
      investigates the possible mechanism by which the interaction between TF and FVIIa
      regulates chemotherapy resistance in neuroblastoma cell lines. METHODS: Gene and
      siRNA transfection was used to enforce TF expression in a TF-negative
      neuroblastoma cell line and to silence endogenous TF expression in a TF
      overexpressing neuroblastoma line, respectively. The expression of TF, Bcl-2,
      STAT5, and Akt as well as the phosphorylation of STAT5 and Akt in gene
      transfected cells or cells treated with JAK inhibitor and LY294002 were
      determined by Western blot assay. Tumor cell growth was determined by a
      clonogenic assay. Cytotoxic and apoptotic effect of doxorubicin on neuroblastoma
      cell lines was analyzed by WST assay and annexin-V staining (by flow cytometry)
      respectively. RESULTS: Enforced expression of TF in a TF-negative neuroblastoma
      cell line in the presence of FVIIa induced upregulation of Bcl-2, leading to
      resistance to doxorubicin. Conversely, inhibition of endogenous TF expression in
      a TF-overexpressing neuroblastoma cell line using siRNA resulted in down
      regulation of Bcl-2 and sensitization to doxorubicin-induced apoptosis.
      Additionally, neuroblastoma cells expressing high levels of either endogenous or
      transfected TF treated with FVIIa readily phosphorylated STAT5 and Akt. Using
      selective pharmacologic inhibitors, we demonstrated that JAK inhibitor I, but not
      the PI3K inhibitor LY294002, blocked the TF/FVIIa-induced upregulation of Bcl-2.
      CONCLUSION: This study shows that in neuroblastoma cell lines overexpressed TF
      ligated with FVIIa produced upregulation of Bcl-2 expression through the
      JAK/STAT5 signaling pathway, resulting in resistance to apoptosis. We surmise
      that this TF-FVIIa pathway may contribute, at least in part, to chemotherapy
      resistance in neuroblastoma.

PMID- 18325116
TI  - ComPath: comparative enzyme analysis and annotation in pathway/subsystem
      contexts.
AB  - BACKGROUND: Once a new genome is sequenced, one of the important questions is to
      determine the presence and absence of biological pathways. Analysis of biological
      pathways in a genome is a complicated task since a number of biological entities
      are involved in pathways and biological pathways in different organisms are not
      identical. Computational pathway identification and analysis thus involves a
      number of computational tools and databases and typically done in comparison with
      pathways in other organisms. This computational requirement is much beyond the
      capability of biologists, so information systems for reconstructing, annotating,
      and analyzing biological pathways are much needed. We introduce a new comparative
      pathway analysis workbench, ComPath, which integrates various resources and
      computational tools using an interactive spreadsheet-style web interface for
      reliable pathway analyses. RESULTS: ComPath allows users to compare biological
      pathways in multiple genomes using a spreadsheet style web interface where
      various sequence-based analysis can be performed either to compare enzymes (e.g.
      sequence clustering) and pathways (e.g. pathway hole identification), to search a
      genome for de novo prediction of enzymes, or to annotate a genome in comparison
      with reference genomes of choice. To fill in pathway holes or make de novo enzyme
      predictions, multiple computational methods such as FASTA, Whole-HMM, CSR-HMM (a
      method of our own introduced in this paper), and PDB-domain search are integrated
      in ComPath. Our experiments show that FASTA and CSR-HMM search methods generally
      outperform Whole-HMM and PDB-domain search methods in terms of sensitivity, but
      FASTA search performs poorly in terms of specificity, detecting more false
      positive as E-value cutoff increases. Overall, CSR-HMM search method performs
      best in terms of both sensitivity and specificity. Gene neighborhood and pathway
      neighborhood (global network) visualization tools can be used to get context
      information that is complementary to conventional KEGG map representation.
      CONCLUSION: ComPath is an interactive workbench for pathway reconstruction,
      annotation, and analysis where experts can perform various sequence, domain,
      context analysis, using an intuitive and interactive spreadsheet-style interface.

PMID- 18325117
TI  - Polymorphism Interaction Analysis (PIA): a method for investigating complex gene
      gene interactions.
AB  - BACKGROUND: The risk of common diseases is likely determined by the complex
      interplay between environmental and genetic factors, including single nucleotide
      polymorphisms (SNPs). Traditional methods of data analysis are poorly suited for
      detecting complex interactions due to sparseness of data in high dimensions,
      which often occurs when data are available for a large number of SNPs for a
      relatively small number of samples. Validation of associations observed using
      multiple methods should be implemented to minimize likelihood of false-positive
      associations. Moreover, high-throughput genotyping methods allow investigators to
      genotype thousands of SNPs at one time. Investigating associations for each
      individual SNP or interactions between SNPs using traditional approaches is
      inefficient and prone to false positives. RESULTS: We developed the Polymorphism
      Interaction Analysis tool (PIA version 2.0) to include different approaches for
      ranking and scoring SNP combinations, to account for imbalances between case and
      control ratios, stratify on particular factors, and examine associations of user
      defined pathways (based on SNP or gene) with case status. PIA v. 2.0 detected 2
      SNP interactions as the highest ranking model 77% of the time, using simulated
      data sets of genetic models of interaction (minor allele frequency = 0.2;
      heritability = 0.01; N = 1600) generated previously [Velez DR, White BC,
      Motsinger AA, Bush WS, Ritchie MD, Williams SM, Moore JH: A balanced accuracy
      function for epistasis modeling in imbalanced datasets using multifactor
      dimensionality reduction. Genet Epidemiol 2007, 31:306-315.]. Interacting SNPs
      were detected in both balanced (20 SNPs) and imbalanced data (case:control 1:2
      and 1:4, 10 SNPs) in the context of non-interacting SNPs. CONCLUSION: PIA v. 2.0
      is a useful tool for exploring gene*gene or gene*environment interactions and
      identifying a small number of putative associations which may be investigated
      further using other statistical methods and in replication study populations.

PMID- 18325118
TI  - Storage and stability of IgG and IgM monoclonal antibodies dried on filter paper
      and utility in Neisseria meningitidis serotyping by Dot-blot ELISA.
AB  - BACKGROUND: A simple filter paper method was developed for, the transport and
      storage of monoclonal antibodies (Mabs) at room temperature or -20 degrees C
      after spotting on filter paper, for subsequent serotyping of outer membrane
      antigens of N.meningitidis by dot-blot ELISA. METHODS: Monoclonal antibodies
      (Mabs) were spotted within a 0.5-1 cm diameter area of Whatman grade 903 paper,
      which were stored individually at room temperature or at -20 degrees C. These
      MAbs were stored and analyzed after periods of one week, 4 weeks, 12 months, or
      13 years in the case of frozen Mab aliquots, or after 4 weeks at -20 degrees C or
      at room temperature (RT) in the case of Mabs dried on filter paper strips. Assays
      were performed in parallel using dot-blot ELISA. In addition to the MAbs specific
      for serotyping class 1, 2 or 3, we used a larger number of Mabs for
      polysaccharides, lipooligosaccharides (LOS), class 5 and cross-reactive antigens
      for native outer membrane of N.meningitidis. The Mabs dried on filter paper were
      eluted with phosphate-buffered saline (PBS) containing 0.2% gelatin. RESULTS:
      Mabs of the isotypes IgG and IgM dried on filter papers were not affected by
      duration of storage. The detection by serotyping Mabs was generally consistent
      for dried filter paper MAb samples stored frozen for over 1 year at -20 degrees
      C, and although decreased reactive antibody titers were found after storage, this
      did not interfere with the specificity of the Mabs used after 13 years as dry
      spots on filter paper. CONCLUSION: The use of filter paper is an inexpensive and
      convenient method for collecting, storing, and transporting Mab samples for
      serotyping studies. In addition, the samples occupy little space and can be
      readily transported without freezing. The efficiency of using immunoglobulin G
      (IgG) or M (IgM) eluted was found to be consistent with measurement of IgG or IgM
      titers in most corresponding, ascites Mabs stored frozen for over 1 year. The
      application of meningococcal typing methods and designations depend on the
      question being asked.

PMID- 18325119
TI  - Computed CD4 percentage as a low-cost method for determining pediatric
      antiretroviral treatment eligibility.
AB  - BACKGROUND: The performance of the WHO recommendations for pediatric
      antiretroviral treatment (ART) in resource poor settings is insufficiently
      documented in routine care. METHODS: We compared clinical and immunological
      criteria in 366 children aged 0 to 12 years in Kinshasa and evaluated a simple
      computation to estimate CD4 percent, based on CD4 count, total white blood cell
      count and percentage lymphocytes. Kappa (kappa) statistic was used to evaluate
      eligibility criteria and linear regression to determine trends of CD4 percent,
      count and total lymphocyte count (TLC). RESULTS: Agreement between clinical and
      immunological eligibility criteria was poor (kappa = 0.26). One third of children
      clinically eligible for ART were ineligible using immunological criteria; one
      third of children immunologically eligible were ineligible using clinical
      criteria. Among children presenting in WHO stage I or II, 54 (32%) were eligible
      according to immunological criteria. Agreement with CD4 percent was poor for TLC
      (kappa = 0.04), fair for total CD4 count (kappa = 0.39) and substantial for CD4
      percent computational estimate (kappa = 0.71). Among 5 to 12 years old children,
      total CD4 count was higher in younger age groups (-32 cells/mm3 per year older),
      CD4 percent was similar across age groups. CONCLUSION: Age-specific thresholds
      for CD4 percent optimally determine pediatric ART eligibility. The use of CD4
      percent computational estimate may increase ART access in settings with limited
      access to CD4 percent assays.

PMID- 18325120
TI  - Basis for treatment of tuberculosis among HIV-infected patients in Tanzania: the
      role of chest x-ray and sputum culture.
AB  - BACKGROUND: Active tuberculosis (TB) is common among HIV-infected persons living
      in tuberculosis endemic countries, and screening for tuberculosis (TB) is
      recommended routinely. We sought to determine the role of chest x-ray and sputum
      culture in the decision to treat for presumptive TB using active case finding in
      a large cohort of HIV-infected patients. METHODS: Ambulatory HIV-positive
      subjects with CD4 counts > or = 200/mm3 entering a Phase III TB vaccine study in
      Tanzania were screened for TB with a physical examination, standard interview,
      CD4 count, chest x-ray (CXR), blood culture for TB, and three sputum samples for
      acid fast bacillus (AFB) smear and culture. RESULTS: Among 1176 subjects 136
      (12%) were treated for presumptive TB. These patients were more frequently male
      than those without treatment (34% vs. 25%, respectively; p = 0.049) and had lower
      median CD4 counts (319/microL vs. 425/microL, respectively; p < .0001). Among the
      136 patients treated for TB, 38 (28%) had microbiologic confirmation, including
      13 (10%) who had a normal CXR and no symptoms. There were 58 (43%) treated
      patients in whom the only positive finding was an abnormal CXR. Blood cultures
      were negative in all patients. CONCLUSION: Many ambulatory HIV-infected patients
      with CD4 counts > or = 200/mm3 are treated for presumptive TB. Our data suggest
      that optimal detection requires comprehensive evaluation, including CXR and
      sputum culture on both symptomatic and asymptomatic subjects.

PMID- 18325121
TI  - Systematic synthesis of community-based rehabilitation (CBR) project evaluation
      reports for evidence-based policy: a proof-of-concept study.
AB  - BACKGROUND: This paper presents the methodology and findings from a proof-of
      concept study undertaken to explore the viability of conducting a systematic,
      largely qualitative synthesis of evaluation reports emanating from Community
      Based Rehabilitation (CBR) projects in developing countries. METHODS: Computer
      assisted thematic qualitative analysis was conducted on recommendation sections
      from 37 evaluation reports, arising from 36 disability and development projects
      in 22 countries. Quantitative overviews and qualitative summaries of the data
      were developed. RESULTS: The methodology was found to be feasible and productive.
      Fifty-one themes were identified and the most important ones of these are
      presented to illustrate the significance of the method. The relative priorities
      of these themes indicated that "management" issues were the primary areas in
      which recommendations were made. Further analysis of themes reflected the
      emphasis evaluators placed on the need for enhanced management, organisational,
      personnel and administrative infrastructure in CBR projects. Evaluators
      consistently recommended that CBR projects should be more connected and
      collaborative at governmental, organisational, political and community levels.
      The synthesis also noted that evaluators questioned the emphasis in CBR on
      project expansion and income generation. CONCLUSION: The application of the
      synthesis methodology utilised in this proof-of-concept study was found to be
      potentially very beneficial for future research in CBR, and indeed in any area
      within health services or international development in which evaluation reports
      rather than formal "research evidence" is the primary source material. The proof
      of-concept study identified a number of limitations which are outlined. Based on
      the conclusions of 37 evaluation reports, future policy frameworks and
      implementation strategies in CBR should include a stronger emphasis on technical,
      organisational, administrative and personnel aspects of management and strategic
      leadership.

PMID- 18325122
TI  - Antenatal care in The Gambia: missed opportunity for information, education and
      communication.
AB  - BACKGROUND: Antenatal care is widely established and provides an opportunity to
      inform and educate pregnant women about pregnancy, childbirth and care of the
      newborn. It is expected that this would assist the women in making choices that
      would contribute to good pregnancy outcome. We examined the provision of
      information and education in antenatal clinics from the perspective of pregnant
      women attending these clinics. METHODS: A cross sectional survey of 457 pregnant
      women attending six urban and six rural antenatal clinics in the largest health
      division in The Gambia was undertaken. The women were interviewed using modified
      antenatal client exit interview and antenatal record review questionnaires from
      the WHO Safe Motherhood Needs Assessment kit. Differences between women attending
      urban and rural clinics were assessed using the Chi-square test. Relative risks
      with 95% confidence intervals are presented. RESULTS: Ninety percent of those
      interviewed had attended the antenatal clinic more than once and 52% four or more
      times. Most pregnant women (70.5%) said they spent 3 minutes or less with the
      antenatal care provider. About 35% recalled they were informed or educated on
      diet and nutrition, 30.4% on care of the baby, 23.6% on family planning, 22.8% on
      place of birth and 19.3% on what to do if there was a complication. About 25% of
      pregnant women said they were given information about the progress of their
      pregnancy after consultation and only 12.8% asked their provider any question.
      Awareness of danger signs was low. The proportions of women that recognised signs
      of danger were 28.9% for anaemia, 24.6% for hypertension, 14.8% for haemorrhage,
      12.9% for fever and 5% for puerperal sepsis. Prolonged labour was not recognised
      as a danger sign. Women attending rural antenatal clinics were 1.6 times more
      likely to recognise signs of anaemia and hypertension as indicative of danger
      compared to women attending urban antenatal clinics. CONCLUSION: Information,
      education and communication during antenatal care in the largest health division
      are poor. Pregnant women are ill-equipped to make appropriate choices especially
      when they are in danger. This contributes to the persistence of high maternal
      mortality ratios in the country.

PMID- 18325123
TI  - GANDivAWeb: a web server for detecting early folding units ("foldons") from
      protein 3D structures.
AB  - BACKGROUND: It has long been known that small regions of proteins tend to fold
      independently and are then stabilized by interactions between these distinct
      subunits or modules. Such units, also known as autonomous folding units (AFUs)
      or"foldons" play a key role in protein folding. A knowledge of such early folding
      units has diverse applications in protein engineering as well as in developing an
      understanding of the protein folding process. Such AFUs can also be used as model
      systems in order to study the structural organization of proteins. RESULTS: In an
      earlier work, we had utilized a global network partitioning algorithm to identify
      modules in proteins. We had shown that these modules correlate well with AFUs. In
      this work, we have developed a webserver, GANDivAWeb, to identify early folding
      units or "foldons" in networks using the algorithm described earlier. The website
      has three functionalities: (a) It is able to display information on the
      modularity of a database of 1420 proteins used in the original work, (b) It can
      take as input an uploaded PDB file, identify the modules using the GANDivA
      algorithm and email the results back to the user and (c) It can take as input an
      uploaded PDB file and a results file (obtained from functionality (b)) and
      display the results using the embedded viewer. The results include the module
      decomposition of the protein, plots of cartoon representations of the protein
      colored by module identity and connectivity as well as contour plots of the
      hydrophobicity and relative accessible surface area (RASA) distributions.
      CONCLUSION: We believe that the GANDivAWeb server, will be a useful tool for
      scientists interested in the phenomena of protein folding as well as in protein
      engineering. Our tool not only provides a knowledge of the AFUs through a natural
      graph partitioning approach but is also able to identify residues that are
      critical during folding. It is our intention to use this tool to study the
      topological determinants of protein folding by analyzing the topological changes
      in proteins over the unfolding/folding pathways.

PMID- 18325124
TI  - A highly conserved segmental duplication in the subtelomeres of Plasmodium
      falciparum chromosomes varies in copy number.
AB  - BACKGROUND: Segmental duplications (SD) have been found in genomes of various
      organisms, often accumulated at the ends of chromosomes. It has been assumed that
      the sequence homology in-between the SDs allow for ectopic interactions that may
      contribute to the emergence of new genes or gene variants through recombinatorial
      events. METHODS: In silico analysis of the 3D7 Plasmodium falciparum genome,
      conducted to investigate the subtelomeric compartments, led to the identification
      of subtelomeric SDs. Sequence variation and copy number polymorphisms of the SDs
      were studied by DNA sequencing, real-time quantitative PCR (qPCR) and fluorescent
      in situ hybridization (FISH). The levels of transcription and the developmental
      expression of copy number variant genes were investigated by qPCR. RESULTS: A
      block of six genes of >10 kilobases in size, including var, rif, pfmc-2tm and
      three hypothetical genes (n-, o- and q-gene), was found duplicated in the
      subtelomeric regions of chromosomes 1, 2, 3, 6, 7, 10 and 11 (SD1). The number of
      SD1 per genome was found to vary from 4 to 8 copies in between different
      parasites. The intragenic regions of SD1 were found to be highly conserved across
      ten distinct fresh and long-term cultivated P. falciparum. Sequence variation was
      detected in a approximately 23 amino-acid long hypervariable region of a surface
      exposed loop of PFMC-2TM. A hypothetical gene within SD1, the n-gene, encoding a
      PEXEL/VTS-containing two-transmembrane protein was found expressed in ring stage
      parasites. The n-gene transcription levels were found to correlate to the number
      of n-gene copies. Fragments of SD1 harbouring two or three of the SD1-genes (o
      gene, pfmc-2tm, q-gene) were also found in the 3D7 genome. In addition a related
      second SD, SD2, of approximately 55% sequence identity to SD1 was found
      duplicated in a fresh clinical isolate but was only present in a single copy in
      3D7 and in other P. falciparum lines or clones. CONCLUSION: Plasmodium falciparum
      carries multiple sequence conserved SDs in the otherwise highly variable
      subtelomeres of its chromosomes. The uniqueness of the SDs amongst plasmodium
      species, and the conserved nature of the genes within, is intriguing and suggests
      an important role of the SD to P. falciparum.

PMID- 18325126
TI  - Spatial and temporal patterning of bank vole demography and the epidemiology of
      the Puumala hantavirus in northeastern France.
AB  - Epidemiological data from bank voles, Myodes glareolus, naturally infected by the
      hantavirus Puumala (PUUV) were collected by a capture-mark-recapture protocol
      from 2000 to 2002 in the French department of Ardennes. Four monitored trapping
      sites were established in two forests located in two cantons (Flize and
      Montherme). We captured 912 bank voles corresponding to 557 different individuals
      during 8820 trapping nights for an overall trapping success of 10.34%. The
      average PUUV seroprevalence was 22.4%. Characteristics of the system reported in
      North European countries are confirmed in France. PUUV seroprevalence and
      abundance of rodents appeared weakly linked. Adult voles were more frequently
      antibody-positive, but no difference between sexes was established. Anti-PUUV
      seropositive voles were captured and high seroprevalence was observed from both
      forests, without human infection reported in Flize canton during the study. One
      site among the four exhibited peculiar infection dynamics, where vole weight and
      infection risk were negatively correlated.

PMID- 18325127
TI  - Absence of Mycobacterium bovis infection in dogs and cats residing on infected
      cattle farms: Michigan, 2002.
AB  - A cross-sectional field study was performed to evaluate infection in dogs and
      cats living on farms with Mycobacterium bovis-infected cattle. The purpose was to
      determine pet infection status and assess their risk to farm families and/or
      tuberculosis-free livestock. Data and specimens were collected from 18 cats and
      five dogs from nine participating farms. ELISA testing for M. bovis and M. avium
      was conducted. Fifty-one biological samples were cultured; all were negative for
      M. bovis, although other Mycobacterium species were recovered. No radiographic,
      serological or skin test evidence of mycobacterial infection was found. These
      negative results may be due to the low level of M. bovis infection in the cattle
      and the limited duration of exposure of pets to infected cattle residing on the
      same farm. No evidence was found to indicate that pets residing on M. bovis
      infected Michigan cattle farms pose a risk to humans or M. bovis-free livestock;
      however, precautionary advice for farm owners was provided.

PMID- 18325125
TI  - The evolution of human influenza A viruses from 1999 to 2006: a complete genome
      study.
AB  - BACKGROUND: Knowledge about the complete genome constellation of seasonal
      influenza A viruses from different countries is valuable for monitoring and
      understanding of the evolution and migration of strains. Few complete genome
      sequences of influenza A viruses from Europe are publicly available at the
      present time and there have been few longitudinal genome studies of human
      influenza A viruses. We have studied the evolution of circulating human H3N2,
      H1N1 and H1N2 influenza A viruses from 1999 to 2006, we analysed 234 Danish human
      influenza A viruses and characterised 24 complete genomes. RESULTS: H3N2 was the
      prevalent strain in Denmark during the study period, but H1N1 dominated the 2000
      2001 season. H1N2 viruses were first observed in Denmark in 2002-2003. After
      years of little genetic change in the H1N1 viruses the 2005-2006 season presented
      H1N1 of greater variability than before. This indicates that H1N1 viruses are
      evolving and that H1N1 soon is likely to be the prevalent strain again.
      Generally, the influenza A haemagglutinin (HA) of H3N2 viruses formed seasonal
      phylogenetic clusters. Different lineages co-circulating within the same season
      were also observed. The evolution has been stochastic, influenced by small
      "jumps" in genetic distance rather than constant drift, especially with the
      introduction of the Fujian-like viruses in 2002-2003. Also evolutionary stasis
      periods were observed which might indicate well fit viruses. The evolution of
      H3N2 viruses have also been influenced by gene reassortments between lineages
      from different seasons. None of the influenza genes were influenced by strong
      positive selection pressure. The antigenic site B in H3N2 HA was the preferred
      site for genetic change during the study period probably because the site A has
      been masked by glycosylations. Substitutions at CTL-epitopes in the genes coding
      for the neuraminidase (NA), polymerase acidic protein (PA), matrix protein 1
      (M1), non-structural protein 1 (NS1) and especially the nucleoprotein (NP) were
      observed. The N-linked glycosylation pattern varied during the study period and
      the H3N2 isolates from 2004 to 2006 were highly glycosylated with ten predicted
      sequons in HA, the highest amount of glycosylations observed in this study
      period. CONCLUSION: The present study is the first to our knowledge to
      characterise the evolution of complete genomes of influenza A H3N2, H1N1 and H1N2
      isolates from Europe over a time period of seven years from 1999 to 2006. More
      precise knowledge about the circulating strains may have implications for
      predicting the following season strains and thereby better matching the vaccine
      composition.

PMID- 18325128
TI  - Ridding London of smallpox: the aerial transmission debate and the evolution of a
      precautionary approach.
AB  - The efforts of the Metropolitan Asylums Board in Victorian London to isolate
      cases of smallpox in hospitals, and so limit its spread, set off a controversy
      about , i.e. alleged escapes of the disease into the neighbourhood. When, in
      1870, the Board began to gather cases of smallpox into its new intra-urban
      isolation hospitals, nearby householders resisted, and in 1881 their fear of
      aerial transmission was endorsed by a government medical inspector, W. H. Power.
      Not all agreed with Power, but as a result from 1885 the Board removed almost all
      known cases of smallpox in London to hospital ships moored in the Thames Estuary.
      The ships failed to provide adequate and secure accommodation, however, and so
      Board smallpox hospitals were erected on the adjacent Dartford marshes. After
      1903, there being no more smallpox epidemics in Britain, these isolation
      hospitals and many similar ones outside other towns and cities were little used
      for their main intended purpose. Their retention for many years thereafter can be
      seen as an application of the precautionary principle; it bears on current
      contingency plans in Britain and elsewhere for dealing with serious epidemics.

PMID- 18325129
TI  - A foodborne outbreak of enterotoxigenic E. coli and Salmonella Anatum infection
      after a high-school dinner in Denmark, November 2006.
AB  - In industrialized countries enterotoxigenic Escherichia coli (ETEC) is mainly
      diagnosed as a cause of travellers' diarrhoea, but it is also known to cause
      foodborne outbreaks. We report an outbreak of acute gastroenteritis caused by
      ETEC serotypes O92:H- and O153:H2 as well as Salmonella Anatum, which affected
      around 200 students and teachers after a high-school dinner in Greater
      Copenhagen, Denmark, November 2006. A retrospective cohort study showed that
      consumption of pasta salad with pesto was associated with an increased risk of
      illness (attack rate 59.4%; risk ratio 2.6, 95% confidence interval 1.2-5.7).
      Imported fresh basil used for preparation of the pesto was the most likely source
      of contamination. Although ETEC is associated with travellers' diarrhoea in
      Denmark, this outbreak suggests that a proportion of sporadic ETEC infections
      might be caused by contaminated imported foodstuffs. To improve food safety
      further, it is important to target this poorly regulated and researched area.

PMID- 18325130
TI  - Neuroborreliosis in the South West of England.
AB  - Although Lyme borreliosis is increasingly diagnosed in the United Kingdom, few
      systematic studies have been performed there. UK data suggest that the commonest
      complications are neurological, but inadequate information exists about their
      nature and the incidence of late neuroborreliosis. Local data are necessary
      because clinical presentations may show geographical variation. This study aimed
      to provide data on clinical manifestations in an area of South West England and
      to estimate treatment delay. We reviewed clinical records of 88 patients in the
      Royal Devon and Exeter Hospital catchment area who had positive Borrelia antibody
      tests during a 5-year period. Fifty-six (64%) reported tick bites. The commonest
      presentations were erythema migrans (65%) and arthralgia/myalgia (27%). However,
      22 patients (25%) had neurological symptoms other than headache alone. Fourteen
      had facial palsy, eight had confusion/drowsiness, four had meningism, five had
      radiculopathy, two had sixth nerve palsies, and two had peripheral neuropathies.
      No late, progressive or atypical neurological syndromes were found. Neurological
      manifestations were generally predictable and usually included either (or all) of
      meningoencephalitis, facial palsy or radiculopathy.

PMID- 18325131
TI  - Dengue virus in Mexican bats.
AB  - Individuals belonging to five families, 12 genera, and 19 different species of
      bats from dengue endemic areas in the Gulf and Pacific coasts of Mexico were
      examined by ELISA, RT-PCR, and for the presence of dengue virus (DV) NS1 protein.
      Nine individuals from four species were seropositive by ELISA: three
      insectivorous, Myotis nigricans (four positives/12 examined), Pteronotus
      parnellii (3/19), and Natalus stramineus (1/4), and one frugivorous Artibeus
      jamaicensis (1/35) (12.86% seroprevalence in positive species). DV serotype 2 was
      detected by RT-PCR in four samples from three species (all from the Gulf coast -
      rainy season): two frugivorous, A. jamaicensis (2/9), and Carollia brevicauda
      (1/2), and one insectivorous, M. nigricans (1/11). The latter was simultaneously
      positive for NS1 protein. DV RT-PCR positive animals were all antibody
      seronegative. M. nigricans showed positive individuals for all three tests. This
      is the first evidence suggesting the presence of DV in bats from Mexico.

PMID- 18325132
TI  - The latent structure of post-traumatic stress disorder: tests of invariance by
      gender and trauma type.
AB  - BACKGROUND: Measurement invariance of Diagnostic and Statistical Manual of Mental
      Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) criterion
      symptoms was tested by gender and trauma type, assaultive and non-assaultive.
      METHOD: Analysis was conducted using latent class analysis (LCA), based on
      findings that the three-class LCA model from Breslau et al. (Archives of General
      Psychiatry 2005, 62, 1343-1351) fits the data across the four groups best. The
      classes represent three levels of PTSD-related disturbance: no disturbance,
      intermediate disturbance and pervasive disturbance, with the last one
      approximating the DSM-IV PTSD diagnosis. RESULTS: Analysis of measurement
      invariance showed that, with respect to gender, there was no evidence of
      differential symptom reporting within the same disturbance class. DSM-IV symptom
      indicators represent the latent structure of PTSD equally in males and females.
      We found that more female than male victims of assaultive violence experienced
      pervasive disturbance. In the absence of measurement variability associated with
      gender, the finding is likely to reflect a gender difference in susceptibility.
      The analysis of measurement invariance detected evidence of variability
      associated with trauma type. Victims of assaultive violence in the pervasive
      disturbance class report more severe distress (especially emotional numbing) than
      do victims of non-assaultive violence in the same class. CONCLUSIONS: The finding
      of measurement bias associated with type of trauma raises questions about the
      applicability of a single definition for PTSD associated with assaultive violence
      and PTSD associated with traumatic events of lesser magnitude.

PMID- 18325133
TI  - Iron status of adolescent girls from two boarding schools in southern Benin.
AB  - Iron deficiency (ID) is the most prevalent micronutrient deficiency in the world,
      particularly in developing countries. Blood samples and a qualitative FFQ on Fe-
      and vitamin C-rich foods were obtained in 180 adolescent girls aged 12 to 17
      years living in two boarding schools from south Benin. ID, defined as serum
      ferritin either 73 micromol/l or transferrin saturation<20%, was found in 32% of
      subjects. Anaemia (Hb<120 g/l) was found in 51% of adolescents, while 24%
      suffered from iron-deficiency anaemia (IDA) (ID and Hb<20 g/l). After adjusting
      for confounding factors (age, mother's and father's occupation, household size)
      in a logistic regression equation, subjects having a low meat consumption (beef,
      mutton, pork) (<4 times/week) were more than twice as likely to suffer from ID
      (OR=2.43; 95% CI 1.72, 3.35; P=0.04). Adolescents consuming less fruits (<4
      times/week) also had a higher likelihood of suffering from ID (OR=1.53; 95% CI
      1.31, 2.80; P=0.03). Finally, subjects whose meat consumption was low were twice
      as likely to suffer from IDA (OR=2.24; 95% CI 1.01, 4.96; P=0.04). The prevalence
      of ID represents an important health problem in these Beninese adolescent girls.
      A higher consumption of Fe-rich foods and of promoters of Fe absorption (meat
      factor and vitamin C) is recommended to prevent ID deficiency in these subjects.

PMID- 18325134
TI  - Refinement and validation of an FFQ developed to estimate macro- and
      micronutrient intakes in a south Indian population.
AB  - OBJECTIVE: Potential error sources in nutrient estimation with the FFQ include
      inaccurate or biased recall and overestimation or underestimation of intake due
      to too many or too few items on the FFQ, respectively. Here we report the
      refinement of an FFQ that overestimated nutrient intake and its validation
      against multiple 24 h recalls. STUDY DESIGN: Data on 2527 participants in south
      India (Trivandrum) were available for the original FFQ (OFFQ) that overestimated
      nutrient intake (132 food items). After excluding participants with implausible
      energy intake estimates (<2.72 MJ/d (<650 kcal/d), >15.69 MJ/d (>3750 kcal/d)) we
      ran stepwise regression analyses with selected nutrients as the outcomes and food
      intake (servings/d) as predictor variables (n 1867). From these results and
      expert consultation we refined the FFQ (RFFQ), and validated it by comparing
      intakes obtained with it and the mean of two 24 h recalls among 100 participants.
      RESULTS: The OFFQ overestimated usual daily nutrient intake before and after
      exclusions [for energy: 13.39 (sd 5.46) MJ (3201 (sd 1305) kcal) and 10.96 (sd
      2.65) MJ (2619 (sd 634) kcal), respectively]. In stepwise analyses, fifty-seven
      food items explained 90 % of the variance in nutrients; we retained thirteen food
      items because participants consumed them at least twice monthly and twelve food
      items that local nutritionists recommended. Mean energy intake estimated from the
      RFFQ (eighty-two food items) was 7.94 (sd 2.05) MJ (1897 (sd 489) kcal). The de
      attenuated correlations between mean 24 h recall and RFFQ intakes ranged from
      0.25 (vitamin A) to 0.82 (fat). CONCLUSION: We refined an FFQ that overestimated
      nutrient intake by shortening and redesigning, and validated it by comparisons
      with 24 h dietary recall data.

PMID- 18325135
TI  - Changes in the sensation of hunger and well-being before and after meals in
      overweight/obese women following two types of hypoenergetic diet.
AB  - OBJECTIVE: To analyse changes in the sensation of hunger and the sensation of
      well-being of young overweight/obese women following two hypoenergetic diets.
      DESIGN, SETTING AND SUBJECTS: Fifty-seven women (BMI = 24-35 kg/m2) were randomly
      assigned to one of two hypoenergetic diets: diet V, in which the consumption of
      vegetables was increased; or diet C, in which the consumption of cereals
      (especially breakfast cereals) was increased. Dietetic and anthropometric data
      and an evaluation of the sensation of hunger and well-being were collected at the
      start and end of the study, 6 weeks later. RESULTS: The diets led to a reduction
      in weight and BMI in both groups. The sensation of hunger at the end of meals was
      higher at the end of the study than at the start in both groups. At 6 weeks, the
      sensation of well-being after breakfast, morning snack and lunch, as well as the
      mean sensation of well-being after all meals, was greater in diet C. Compared
      with that recorded at the beginning of the study, the capacity to experience
      satiety at the end of meals also increased with diet C, as did the capacity to
      experience well-being at 6 weeks (for breakfast, lunch, dinner and for the mean
      for all meals). This capacity to experience well-being was also greater in diet C
      than in diet V with respect to the mid-morning snack and lunch. CONCLUSION: The
      more positive results obtained with diet C may contribute to the increased weight
      loss seen in that group and their lower withdrawal rate.

PMID- 18325136
TI  - Experimental approach to measuring functional food consumption for risk factor
      surveillance.
AB  - OBJECTIVE: To develop and integrate the assessment of functional foods (FuF;
      manufactured foods with altered composition carrying a health claim) consumption
      into an existing risk factor surveillance system. DESIGN: FuF market research
      followed by an experimental FuF intake study incorporated into an ongoing
      community-based survey. Concurrent completion of a self-administered semi
      quantitative FFQ and a self-administered, qualitative FuF frequency questionnaire
      (FuFFQ) followed by a face-to-face control step using FuF photographs and
      combined food group-based data analyses. SETTING: 'Bus Sante' risk factor
      surveillance programme, Geneva/Switzerland. SUBJECTS: Population-based random
      sample of 639 residents (52 % women, aged 35-74 years) surveyed from September
      2003 to April 2004. RESULTS: Local Geneva/French neighbourhood market research
      identified 148 FuF in five major FuF food groups which were compiled into a
      functional ingredient database. Prior to the face-to-face verification, 210 (33
      %) individuals categorized themselves as FuF consumers, 429 (67 %) as non
      consumers. The control step revealed that 70 % of the 639 participants were
      already familiar with the FuF concept, and thus were correctly self-categorized
      as FuF consumers or non-consumers. For the remaining 30 % of participants the
      true FuF consumption status was established, resulting in a final number of 285
      FuF consumers (45 %; 12 % net increase) and 354 (55 %) non-consumers.
      CONCLUSIONS: The developed self-administered, brief, qualitative food group-based
      FuF frequency check list in combination with an FFQ and a photo-assisted control
      step provides a flexible assessment tool for measuring FuF consumption in the
      context of a specific fluctuating FuF market and may be applicable to other
      population settings and times.

PMID- 18325137
TI  - A comparative study of selenium concentration and glutathione peroxidase activity
      in normal and breast cancer patients.
AB  - OBJECTIVE: The present study was undertaken to compare plasma Se values and
      glutathione peroxidase (GPX) activity in normal and breast cancer patients.
      DESIGN: In a case-control study, forty-five breast cancer patients and the same
      number of healthy women were randomly selected from their population. Se was
      measured in plasma by atomic absorption spectrophotometry and GPX activity in
      erythrocytes was measured using a standard spectrophotometric method. RESULTS:
      Plasma Se concentration in healthy women and breast cancer patients was in the
      normal range, with no statistically significant difference observed between the
      two groups (138.40 (sd 40.36) microg/l v. 132.15 (sd 35.37) microg/l,
      respectively). Erythrocyte GPX activity was significantly (P<0.01) higher in
      breast cancer patients (24.81 (sd 11.66) U/g Hb) compared with healthy women
      (20.29 (sd 4.24) U/g Hb). CONCLUSION: The present study indicated that Se
      deficiency was not a problem in the participants, and sufficient quantity of this
      element could increase GPX activity to have a protective effect against oxidative
      damage.

PMID- 18325138
TI  - Five-year incidence of obesity and its determinants: the ATTICA study.
AB  - OBJECTIVES: To evaluate the 5-year incidence of obesity in a sample of CVD-free
      adults and investigate the potential effect of several sociodemographic and
      lifestyle habits on weight change and obesity incidence in these individuals.
      METHODS: Men (n 1514) and women (n 1528) (>18 years) without any clinical
      evidence of CVD, living in the Attica area of Greece, were enrolled in the ATTICA
      study from May 2001 to December 2002. The sampling was random, multistage and
      included information about various sociodemographic, lifestyle (diet, exercise
      and smoking), biochemical and clinical characteristics. In 2006, the 5-year
      follow-up was performed through telephone calls or personal visits. Data from the
      1364 participants are analysed in the present work. RESULTS: The 5-year incidence
      of obesity was 21.8 % in men and 11.9 % in women. The ratio of men to women
      revealed that more men than women developed obesity, while more women than men
      became overweight during the follow-up period. It was found that men were 1.6
      times more likely to develop obesity compared with women; abnormal waist
      circumference, smoking habits and the presence of hypercholesterolaemia increased
      the risk for developing obesity, irrespective of age and baseline lifestyle
      characteristics of the participants. In the multivariate analysis, no association
      was detected between adherence to a Mediterranean diet and incidence of obesity
      in initially normal-weight individuals. CONCLUSIONS: Obesity remains a serious
      health problem for the Greek population; the alarming rates of excess body weight
      continue to increase. Preventive measures should be urgently addressed, targeting
      particularly those with metabolic risk factors.

PMID- 18325139
TI  - Perioperative placement of stents for relief of proximal pulmonary arterial
      stenoses in infants.
AB  - INTRODUCTION: Stenoses in the pulmonary arterial system can have a significant
      negative impact on the early postoperative course in infants. Early recognition
      and aggressive management are mandatory. PATIENTS AND METHODS: We describe our
      experience with 8 infants, with ages ranging from 3 to 9 months, weighing from
      4.5 to 7.7 kilograms, who presented in the up to 18 days following construction
      of a shunt from the superior caval vein to the pulmonary arteries with clinical
      symptoms of obstructed pulmonary flow. We include also 2 infants in whom
      pulmonary arterial stents were implanted in the operating room. Cardiac
      catheterization showed significant stenoses or occlusion of the left pulmonary
      arteries in 9 infants, the right pulmonary arteries in 2, or the superior caval
      vein in 1, the investigation being prompted by the findings of supraphysiological
      superior caval venous pressures and systemic hypoxaemia. We implanted a variety
      of stents mounted on balloons ranging in diameter from 6 to 13 millimetres, with
      7 placed across a newly created surgical anastomotic site. RESULTS: All stenoses
      were crossed successfully, and stents implanted satisfactorily in all patients,
      albeit that 1 infant suffered an acute tear of the left pulmonary artery,
      requiring immediate reoperation. This patient died 72 hours later due to a
      diffuse coagulopathy. All other patients demonstrated sustained clinical
      improvement following the procedure. At follow-up, 7 of the 9 survivors have
      progressed to completion of the Fontan circulation. Redilation of the stents was
      required in the interim, prior to completion of the Fontan circulation, in 4 of
      them. In 2 patients, the previously implanted stents were incised during the
      Fontan completion, permitting placement of the extracardiac Goretex conduit from
      the inferior caval vein to the pulmonary arteries. CONCLUSIONS: Stents can
      successfully be implanted perioperatively in the pulmonary arterial system during
      infancy, and redilated, with improvement in clinical outcome in the majority of
      those with clinically relevant obstruction.

PMID- 18325140
TI  - Levels of vasopressin in children undergoing cardiopulmonary bypass.
AB  - OBJECTIVES: It is accepted treatment to give vasopressin to adults in
      postcardiotomy shock, but such use in children is controversial. Cardiopulmonary
      bypass is presumed to attenuate the normal endogenous vasopressin response to
      shock. We hypothesized that levels of vasopressin in children are altered by
      bypass, and that children having low endogenous levels perioperatively are more
      likely to develop hypotension, or require vasopressors. METHODS: Serial levels of
      vasopressin were assessed prospectively in children undergoing bypass at a single
      center. RESULTS: Of 61 eligible patients, we enrolled 39 (63%). Their median age
      was 5 months. The mean level of vasopressin prior to bypass was 18.6 picograms
      per millilitre, with an interquartile range from 2.6 to 11.4. Levels of
      vasopressin peaked during bypass at 87.1, this being highly significant compared
      to baseline (p < 0.00005), remained high for 12 hours at a mean of 73.5, again
      significantly different from baseline (p = 0.002), were falling at 24 hours, with
      a mean of 28.1 (p = 0.04), and had returned to baseline by 48 hours, when the
      mean was 7.4 (p = 0.3). Age, gender, and the category for surgical risk had no
      influence on the levels of vasopressin. There was no statistically significant
      relationship between the measured levels and hypotension or the requirement for
      vasopressors, although a few persistently hypotensive patients had high levels
      subsequent to bypass. Higher levels correlated with higher levels of sodium in
      the serum (r(s) = 0.37, p < 0.00005), higher osmolality (r(s) = 0.37, p <
      0.00005), and positive fluid balance (r(s) = 0.23, p < 0.008). Preoperative use
      of inhibitors of angiotensin converting enzyme, preoperative congestive cardiac
      failure, and longer periods of bypass predicted higher levels during the first
      eight postoperative hours. CONCLUSIONS: Children do not have deficient endogenous
      levels of vasopressin following bypass, and lower levels are not associated with
      hypotension. Any therapeutic efficacy of infusion of vasopressin for post
      cardiotomy shock in children is likely due to reasons other than physiologic
      replacement.

PMID- 18325141
TI  - Results with continuous cardiopulmonary bypass for the bidirectional
      cavopulmonary anastomosis.
AB  - OBJECTIVE: Some centres have proposed creating the bidirectional cavopulmonary
      anastomosis without cardiopulmonary bypass, while others continue to use deep
      hypothermic circulatory arrest. The purpose of this review is to evaluate the
      results of using continuous cardiopulmonary bypass with moderate hypothermia,
      perhaps the most commonly used of the three techniques for this procedure.
      METHODS: Between 1990 and 2005, 114 patients, having a mean age of 1.58 years,
      with a median age of 8 months, and ranging from 3 months to 16 years, underwent
      creation of either a unilateral cavopulmonary anastomosis, in 94 cases, or
      bilateral anastomoses in 20 cases. All had continuous cardiopulmonary bypass with
      moderate hypothermia at 32 degrees Celsius, with 24 also having aortic cross
      clamping with cardioplegia for simultaneous intracardiac procedures. Interrupted
      absorbable sutures were used to create the anastomosis in 105 patients. RESULTS:
      Perioperative mortality was 5%, with 6 of the patients dying. The mean period of
      cardiopulmonary bypass for an isolated anastomosis was 91 minutes, with a range
      from 44 to 160 minutes. In 10 patients (8.8%), it was necessary to place a graft
      to augment the anastomosis. The average postoperative length of stay was 7.9 days
      for those undergoing an isolated unilateral anastomosis, and 16.4 days for
      patients undergoing combined cardiac operations. We have now created the Fontan
      circulation in 79 of the patients, at an average interval from the bidirectional
      cavopulmonary anastomosis of 2.1 plus or minus 1.14 years. In 76 patients, we
      performed postoperative angiograms, and none revealed any stenoses. CONCLUSIONS:
      The bidirectional cavopulmonary anastomosis can be performed successfully with
      continuous cardiopulmonary bypass and moderate hypothermia with a beating heart,
      avoiding circulatory arrest. The use of interrupted and absorbable sutures was
      not associated with any late anastomotic stenosis.

PMID- 18325142
TI  - Role of caval venous manipulation in treatment of protein-losing enteropathy.
AB  - Protein-losing enteropathy has been associated with the Fontan operation,
      restrictive cardiomyopathy, constrictive pericarditis, tricuspid valvar stenosis
      and insufficiency, and superior caval venous obstruction. The mechanism of
      development of this complication of cardiac disease likely is multifactorial. We
      report here our experience with 3 patients with protein-losing enteropathy. Two
      had superior caval venous occlusion. The third patient had undergone an
      extracardiac Fontan operation, with stenosis of the extracardiac conduit placed
      to the right pulmonary artery. In all three cases, the complication was resolved
      by restoring unobstructed flow of blood in the superior or inferior caval vein.
      Since the aetiology of protein-losing enteropathy associated with cardiac disease
      is multifactorial, reduction of pressure in the tributaries of the superior caval
      vein may, in some cases, be curative. It is more difficult to cure the problem
      when it is associated with the Fontan operation.

PMID- 18325143
TI  - Does cardioplegia leave room for postconditioning in paediatric cardiac surgery?
AB  - BACKGROUND: Postconditioning by brief episodes of ischaemia performed just at the
      time of reperfusion have been shown to reduce the size of infarcts in animal
      models, and in the clinical setting of percutaneous cardiac intervention. The
      clinical applicability of postconditioning in cardiac surgery remains to be
      determined. We investigated the effect of postconditioning on myocardial
      protection in children undergoing cardiac surgery. METHODS: We randomly assigned
      40 patients scheduled for surgical correction of congenitally malformed hearts
      under cold blood cardioplegic arrest to postconditioning or control treatment.
      Postconditioning was performed by two cycles of 30 seconds ischaemia and 30
      seconds reperfusion using aortic reclamping, and declamping started 30 seconds
      after cardioplegic arrest. We assayed creatine kinase-MB, troponin I,
      transcardiac release of lactate and neutrophil counts. RESULTS: The types of
      procedure, age, bypass and aortic cross-clamping times were similar in both
      groups. The postoperative peaks of creatine kinase-MB and troponin I were lower
      after aortic de-clamping in the postconditioned patients compared with their
      controls (128 +/- 48 units per liter as opposed to 199 +/- 79 units per liter, p
      = 0.016, and 0.34 +/- 0.21 nanograms per milliliter as opposed to 0.61 +/- 0.53
      nanograms per milliliter, p = 0.05), with reduced inotropic scores in those
      submitted to postconditioning compared with their controls (4.8 +/- 3.1 versus
      2.3 +/- 1.5, p = 0.036). Transcardiac release of lactate was reduced in the
      postconditioned patients compared with their controls (0.10 +/- 0.27 as opposed
      to 0.37 +/- 0.43 millimols per liter, p = 0.048). No differences between groups
      were found for transcardiac neutrophil count during reperfusion (10.8 +/- 6.3%
      for postconditioning versus 14.0 +/- 8.7% for controls, p = 0.48). CONCLUSIONS:
      Our study demonstrates that postconditioning may protect the myocardium of
      children undergoing cold blood cardioplegic arrest. These data support the need
      for a larger clinical trial of postconditiong in children undergoing cardiac
      surgery.

PMID- 18325144
TI  - Patterns of use of educational and rehabilitation services at school age for
      children with congenitally malformed hearts.
AB  - BACKGROUND: Infants with congenitally malformed hearts who require early open
      heart surgery are at high risk for developmental, psychosocial, and academic
      difficulties. Our objective was to describe the pattern of use of educational
      supports and rehabilitation services in these children at early school age.
      METHODS: Parents of children who participated in a prospective study of
      developmental progress following open-surgery were contacted to participate in a
      telephone survey. The questionnaire included questions regarding current
      educational and rehabilitation resources their child was receiving, as well as
      the needs perceived by the parents for services, and obstacles to accessing
      services. RESULTS: The survey was completed by 60 families, the mean age of the
      children being 8.1 years, with standard deviation of 1.1 years. Of the children,
      22% received educational supports, which primarily included supplemental
      tutoring. Rehabilitation services were received by 23%, speech therapy for 9
      children, psychologic support for 6, occupational therapy for 3, and physical
      therapy for 1. Children receiving these services were significantly more likely
      to have had low developmental scores in the expected domains, when compared to
      those not receiving services. The majority of developmentally delayed children
      were not receiving adequate, if any, resource support. Medical and surgical
      history was not associated with greater likelihood of receipt of services.
      CONCLUSIONS: Children with congenitally malformed hearts who are now of school
      age are at risk for developmental challenges and academic difficulties, yet many
      do not receive services to optimize performance. Modification of current practice
      to include systematic, periodic screening, as well as the availability of a
      resource person for information and referral, may be warranted to meet the
      ongoing needs of these children and their families, and to optimize their health
      and well-being.

PMID- 18325145
TI  - Takayasu's disease: a review.
AB  - Takayasu's disease is a rare chronic vasculitis of unknown aetiology. Initial
      symptoms and signs are non-specific, and a high index of suspicion is needed to
      make the correct diagnosis. The disease is associated with a high incidence of
      morbidity, and a significant risk of premature death. Serological tests have
      proved unreliable in distinguishing active from quiescent disease, with non
      invasive imaging currently offering the best option for early diagnosis, and
      monitoring the response to treatment. In this review, we detail the epidemiology,
      pathophysiology, clinical features, imaging characteristics, and currently
      available treatments.

PMID- 18325146
TI  - In situ lymph dynamic characterization through lymph nodes in rabbit hind leg:
      special reference to nodal inflammation.
AB  - In some lymph nodes, water and water-soluble substances of smaller molecular
      weight are known to be absorbed into blood vessels, and consequently the protein
      concentration of lymph within the nodes increases. In this study, we examined
      pressure-flow relationships of lymph nodes in situ and exchange properties of
      water and water-soluble substances through the nodes with special reference to
      inflamed lymph nodes. A lymph perfusion model through the lymph node in situ was
      constructed by cannulating one of the afferent lymphatics and an efferent
      lymphatic. Increasing infusion pressure (0 to 150 cmH(2)O) or decreasing outflow
      pressure (10 to -5 cmH(2)O) in the model caused a significant increase of the
      lymph outflow rate through the node. This rate was also increased significantly
      with increases in both intranodal venous pressure (range: control, 20, 30, and 40
      mmHg) and prenodal lymph albumin concentration (range: 0%, 2.6%, and 10%). When
      formyl-Met-Leu-Phe-OH (fMLP)-mediated acute inflammation was produced in the
      lymph nodes, the lymph outflow rate through the node was significantly decreased.
      These results indicate that colloid osmotic pressure and hydrostatic pressure
      within the lymph node may play important roles in the transport of water and
      water-soluble substances through the node. Acute fMLP-mediated inflammation of
      lymph nodes also produced a significant decrease of the lymph flow rate through
      lymph nodes.

PMID- 18325147
TI  - Medical autonomy: peeling the onion.

PMID- 18325148
TI  - Academic health centres: what is the agenda for research?

PMID- 18325150
TI  - Loss of doctor-to-doctor communication: lessons from the reconfiguration of
      mental health services in England.
AB  - OBJECTIVE: To explore the tensions across the primary-secondary interface when
      referral from primary care is to a team and to inform service developments in
      other specialties. METHODS: A nested qualitative study within a randomized
      controlled trial of primary care and Community Mental Health Teams (CMHTs) in
      Croydon and Manchester, UK. For the qualitative study, interviews were carried
      out with general practitioners (GPs), psychiatrists and managers or clinical
      leads of the CMHTs. RESULTS: GPs described the need for access to specialist
      knowledge, which they perceived to lie with the psychiatrist, and referral to a
      team was not perceived to allow this access. A personal threshold was identified
      by GPs after which they referred the patient to secondary care. CMHTs and
      psychiatrists recognized that this personal threshold differed between GPs, but
      their criteria for accepting referrals did not seem to allow for a flexible
      response to referral requests, leading to the referral being labelled as
      'inappropriate'. The lack of direct doctor-to-doctor communication was perceived
      by respondents to contribute to a fragmentation of patient care. Strategies were
      described whereby the system was bypassed to achieve doctor-to-doctor
      communication, which undermined the team. CONCLUSIONS: Development of
      intermediate or 'Tier 2' services beyond the mental health services, where the GP
      refers to a team rather than to a specialist (hospital consultant) could benefit
      from reflecting on experiences with mental health services. There is a danger
      that new community services for the physically ill will engender the same level
      of confusion and discontent described by GPs and other health professionals in
      this study who are concerned with mental health care. Flexibility is needed
      within care pathways, including the provision of direct doctor-to-doctor
      communication together with approaches to minimize the marginalization of non
      medical professionals.

PMID- 18325151
TI  - 'Nurse entrepreneurs' a case of government rhetoric?
AB  - INTRODUCTION: Nursing has come to play a prominent role in government health
      policy since 1997. Extending the scope of nursing practice into activities
      previously carried out by doctors can assist a managerialist and 'modernizing'
      project of increasing National Health Service (NHS) efficiency by removing
      demarcations between professional groups. METHODS: Drawing on elements of
      poststructuralist linguistics, this paper presents an analysis of a key
      government speech in the context of a discussion of overall policy intentions.
      RESULTS: The speech can be seen as an example of how government has attempted to
      use rhetoric to make its goals attractive to nurses. CONCLUSION: Policy-makers
      have to make their policies acceptable to those whom they expect to implement
      them. In this case, organizational efficiency, chiefly in terms of broader access
      to NHS services, as well as role substitution, is aligned with government policy
      promoting social enterprise and 'sold' to the nursing profession as enhancing its
      status compared with medicine.

PMID- 18325152
TI  - Citizen and staff involvement in health service decision-making: have National
      Health Service foundation trusts in England given stakeholders a louder voice?
AB  - OBJECTIVES: National Health Service (NHS) foundation trusts have been created to
      decentralize the management of NHS provider organizations through the
      substitution of central government control with local accountability to citizens
      and employed staff. Our aim was to explore the roles adopted by elected and
      appointed governors of a first wave NHS foundation trust and the extent to which
      governors shared power with trust directors and influenced the management of the
      trust. METHODS: A one-year case study of a single NHS foundation trust (Homerton
      Hospital in East London) was conducted. Data were collected using face-to-face
      interviews with a sample of governors and directors, as well as through non
      participant observation of public and private meetings of governors and
      documentary analysis. RESULTS: Governors and directors found the new role of
      foundation trust governor ambiguous and difficult to define. This lack of clarity
      impeded the development of the new governance function. Governors perceived that
      they had made little impact on the decisions of the Trust during the year of
      study. However, evidence was found of an increased involvement of governors and
      the public in the activities of the Trust. CONCLUSIONS: Government plans to
      decentralize accountability of public hospitals to local communities appear
      problematic, at least in the short term. Unless the effectiveness of the new
      local governance arrangements is addressed, an accountability 'gap' may emerge as
      prior mechanisms for public accountability to the centre are dismantled. In these
      circumstances, decentralization may lead in practice to a loss of public
      accountability.

PMID- 18325153
TI  - The effect of age and procedure on resource use for patients with cerebrovascular
      disease.
AB  - OBJECTIVE: Many studies have described the impact of population ageing on health
      care expenditures, but few have assessed its impact on specific diseases adjusted
      for severity and procedure. This study examined the relationship between an
      ageing population and resource use in patients with cerebrovascular disease
      (CVD). METHODS: A total of 13,856 CVD patients were treated in 82 academic and 92
      community hospitals. Demographic variables, clinical variables, length of stay
      (LOS) and total charges were analysed by age group (under 65 years, 65-74 years
      and 75 years or older). The independent effects of age on LOS and total charge
      were determined using multivariate analysis. RESULTS: There were 5172 (37%)
      patients under 65 years of age, 4096 (30%) 65-74 years and 4588 (33%) 75 years or
      older. Intracranial infarction or ischaemia was diagnosed in 69% of the patients,
      haemorrhage in 23% and subarachnoid haemorrhage in 9%. The overall mortality was
      6% (5% in under 65 years, 5% in 65-74 years and 9% in 75 years or older;
      P<0.001). There were significant differences in the proportion of procedures
      performed in each age category. Age and procedure were significantly associated
      with LOS, particularly the latter. Age had no significant association with total
      charge, but procedure was highly associated. CONCLUSIONS: Ageing has no
      significant impact on total charge. Instead policy-makers should acknowledge the
      effect of procedures on health care costs, conduct economic evaluations and
      monitor use of procedures.

PMID- 18325154
TI  - Improving access to primary care: eight case studies of introducing Advanced
      Access in England.
AB  - OBJECTIVE: To examine the implementation of 'Advanced Access' as a means of
      improving access to primary care. METHODS: Qualitative case studies of eight
      English general practices undertaken as part of a mixed method study. RESULTS:
      There was considerable variation in the interpretation and implementation of
      Advanced Access. Practices claiming to operate this system often did not follow
      its key principles. Differences between practice access systems centred on the
      use of 'same-day' appointments. The association of Advanced Access with same-day
      appointment systems was problematic as it both created antagonism to, and
      diverged from, the Advanced Access model. Practice staff did not necessarily
      share the conceptualisation of demand that underpinned Advanced Access. Other
      policies and targets provided further incentives to diverge from the model and
      these factors were compounded by informal organizational behaviours, notably the
      exercise of discretion, which led to adaptation. CONCLUSION: Advanced Access was
      diluted because it became confused with same-day appointment systems and other
      incentives and targets. Its guiding philosophy of 'manageable demand' appeared
      counter-intuitive to staff in the context of general practice, which made its
      implementation problematic. As a result, the system was adapted and modified.

PMID- 18325155
TI  - Recognizing rhetoric in health care policy analysis.
AB  - Critiques of the 'naive rationalist' model of policy-making abound in the
      sociological and political science literature. Yet academic debate on health care
      policy-making continues to be couched in the dominant discourse of evidence-based
      medicine, whose underlying assumptions--that policies are driven by facts rather
      than values and these can be clearly separated; that 'evidence' is context-free,
      can be objectively weighed up and placed unproblematically in a 'hierarchy'; and
      that policy-making is essentially an exercise in decision science--have
      constrained both thinking and practice. In this paper, drawing on theoretical
      work from political science and philosophy, and innovative empirical work in the
      health care sector, we argue that health care is well overdue for a re-defining
      of what policy-making is. Policy-making is the formal struggle over ideas and
      values, played out by the rhetorical use of language and the enactment of social
      situations. While the selection, evaluation and implementation of research
      evidence are important in the policy-making process, they do not equate to that
      process. The study of argument in the construction of policy has the potential to
      illuminate dimensions of the process that are systematically occluded when policy
      making is studied through a naive rationalist lens. In particular, a rhetorical
      perspective highlights the struggle over ideas, the 'naming and framing' of
      policy problems, the centrality of audience and the rhetorical use of language in
      discussion to increase the audience's adherence to particular framings and
      proposals. Rhetorical theory requires us to redefine what counts as 'rationality'
      -which must extend from what is provably true (by logic) and probably true (by
      Bayesian reasoning) to embrace, in addition, that which is plausibly true (i.e.
      can convince a reasonable audience). Future research into health care policy
      making needs to move beyond the study of 'getting evidence into practice' and
      address the language, arguments and discourse through which policy is constructed
      and enacted.

PMID- 18325157
TI  - Will reputational incentives stimulate a reversal of the physician brain drain?
AB  - An increased supply of physicians in high income countries both from domestic
      production and from immigration from low and middle income countries has made
      medical employment increasingly competitive. This has been heightened by the
      introduction of reputational incentives, such as public reporting of physicians'
      outcomes, and the use of other health care professionals, such as nurses. An
      unanticipated consequence might be a reversal of the 'brain drain', with
      physicians migrating to low and middle income countries.

PMID- 18325161
TI  - Creating receptor capacity for research in the health system: the Executive
      Training for Research Application (EXTRA) program in Canada.

PMID- 18325162
TI  - Implementing a balanced scorecard as a strategic management tool in a long-term
      care organization.
AB  - BACKGROUND: The Capital Care Group, the largest public sector continuing care
      organization in Canada, had no ready access to information on its own performance
      and therefore was limited in its pursuit of evidence-informed decision-making. To
      remedy this, it was decided to introduce a balanced scorecard. ASSESSMENT OF
      PROBLEM: A literature review was conducted together with interviews with 10 other
      health care organizations which had implemented balanced scorecards. With this
      information, a workshop was held that resulted in a framework and about 120
      potential indicators. Subsequently the number of indicators was reduced to 29,
      using pre-determined criteria. RESULTS: Development of a corporate balanced
      scorecard facilitated executive strategic thinking and clarified the
      organization's strategic direction. In parallel, scorecards were developed at the
      level of care centres. These had a common core of indicators, plus some site
      specific ones. Development of the corporate scorecard took three years and an
      additional six months for the care centre scorecards. STRATEGIES FOR CHANGE: A
      formal implementation plan has been accepted by the executive team. Key to this
      is communicating to staff the role of scorecards for strategic management and not
      just performance measurement. Traditional thinking needs to change from a short
      term operational focus to long-term strategy. In addition, champions need to be
      identified in each care centre and they need to be networked together. Finally,
      the scorecard is being integrated into existing operational management as a
      routine component together with resources to support its use. LESSONS AND
      MESSAGES: The balanced scorecard has focused on its role as a strategic
      management tool. The indicators and dimensions need to be customized to the
      organization. Senior management must be seen to be driving its introduction. It
      is worth spending sufficient time developing and implementing a scorecard rather
      than trying to rush its introduction. The scorecard needs to be integrated with
      existing management processes and sufficient resources must be assigned. However,
      success will ultimately depend on the culture of the organization being
      appropriate and receptive.

PMID- 18325163
TI  - Bridging the gap between primary and secondary care: use of a clinical pathway
      for the investigation and management of deep vein thrombosis.
AB  - BACKGROUND: Clinical processes that span the boundary between primary and
      secondary care often suffer from poor standardization of practice and lines of
      communication. One example is the clinical management of suspected deep vein
      thrombosis (DVT). Making or excluding the diagnosis can be complex. Tools to
      investigate DVT were not available to family physicians so patients had to be
      referred to the hospital emergency department and endure a long wait which could
      exacerbate the condition. In addition, urgent referrals to the ultrasound
      department disrupted the scheduled list of patients. ASSESSMENT OF PROBLEM: A
      team of stakeholders including all relevant specialties and professions from
      primary and secondary care was established. After reviewing the literature and
      interviewing those involved in delivering care, an evidence-based scoring system
      to calculate the clinical probability of a DVT was adopted and introduced as part
      of a clinical pathway from primary to secondary care. Its introduction was based
      on the Plan, Do, Study, Act (PDSA) cycle. RESULTS: In the first year after the
      introduction of the clinical pathway, 70% of family physicians had used it and
      were very satisfied. Patients found it efficient (75%) with 96% very satisfied or
      satisfied. The waiting time in the emergency department fell from a mean of 379
      minutes to 285 minutes. Although the incidence of initial investigations (D-Dimer
      tests) increased by 42%, the proportion of patients undergoing a subsequent
      ultrasound test found to have a DVT was unchanged (14%). This suggested the level
      of suspicion of a DVT in the community had risen. Referrals to the hospital's DVT
      clinic increased by 14% overall, driven partly by a large increase in those who
      had come from the new clinical pathway from primary care. LESSONS AND MESSAGES:
      Key lessons include the importance of including all relevant stakeholders and the
      benefits of using PDSA to make rapid changes during implementation. We are now
      seeking to extend the use of the clinical pathway to other hospitals and more
      family physicians. In addition, the clinical pathway approach will be applied to
      other conditions and interventions. We have demonstrated how a multidisciplinary
      group of stakeholders in a clinical care process can develop and introduce a
      clinical pathway that allows smooth transit of patients over the barriers between
      different sectors of the health care system and between independent disciplines.
      We have also demonstrated the use of untapped non-physician potential in the
      system to safely facilitate patient care.

PMID- 18325164
TI  - Moving to a culture of safety in community home health care.
AB  - OBJECTIVE: Community home health care workers and their clients are faced with a
      mixture of occupational health and safety challenges that are not typically
      experienced by health care providers or patients in the acute care sector. The
      aim of this project was to explore the concept of safety in community home health
      in one health care authority in British Columbia. METHODS: A participatory action
      research approach was employed to explore staff and client safety risks in this
      environment. In the first phase, three focus groups were held with staff (n = 39)
      and the data analysed to identify themes. These were validated by additional
      focus groups. In the second phase, interviews were held with staff followed by
      chart reviews. Finally, in phase three, an interdisciplinary working group
      developed a risk identification tool for staff which was subsequently piloted.
      The exploration focused on answering the following questions: What constitutes
      safety in community home health care? What are the priority areas for action in
      relation to safety? What type of risk identification would be most helpful to
      community health workers to prepare them adequately to meet their clients' and
      their own safety needs? RESULTS: Risk themes identified included: poor
      communication, acute care staff not understanding the needs of community staff,
      working alone, mobility, medication concerns, lack of pre-screening of clients'
      homes, and community health workers accepting a high degree of risk. CONCLUSIONS:
      Findings suggest that typical notions of safety and risk in acute care are not
      easily translated into the community sector, that staff and clients' safety
      concerns are intertwined, and staff require better and more timely information
      from acute care staff when patients are discharged home.

PMID- 18325165
TI  - Improving the nutritional status of elderly residents of long-term care homes.
AB  - INTRODUCTION: High rates of malnutrition exist in long-term care residents in
      Canada. Residents may be admitted in a malnourished state or may become
      malnourished while in care. Nutritional decline of residents may be due to
      medical conditions but may also result from the failure to provide for the unique
      nutritional needs of this population, through an inadequate menu, inadequate
      swallowing and functional assessments, and lack of assistance with dining.
      ASSESSMENT OF PROBLEM: A project for the implementation of regional food services
      policies and practices was deployed with the ultimate goals to reduce nutritional
      risk and enhance the quality of life of the individuals residing in the 29 long
      term care homes in the Saskatoon Health Region. The objectives were: to ensure
      that food and nutrition staff were competent; to provide adequate nutrition to
      residents; and to ensure nutrition screening, assessment and appropriate
      intervention, as approved by the resident or their relatives, was provided.
      Implementation consisted of: extensive communication of the problem; the
      development of draft Saskatchewan Food Services policies; planning regional
      goals, tasks, accountabilities and indicators; delivering meal assistance
      training to staff; and establishing a Regional Menu Advisory Committee. RESULTS:
      Outcomes have been clearly articulated and methods to collect data clearly
      defined. Interventions in progress include: the development of key relationships
      among the health region's long-term care staff, managers and directors;
      communicating a clear understanding of resident-directed care; determining the
      baseline knowledge of food service staff; and assembling a project tool kit for
      implementing food and nutrition policies at each home. STRATEGIES FOR QUALITY
      IMPROVEMENT: Although the expectation was that food services policy
      implementation would be presented to all homes simultaneously, a more intensive
      pilot schedule has focussed on early-adopter sites. The three-year implementation
      plan is designed for sustainability. LESSONS AND MESSAGES: Malnutrition is
      multifactorial and a concerted effort of all caregivers and service providers is
      important to address root causes.

PMID- 18325166
TI  - Improving performance management for delivering appropriate care for patients no
      longer needing acute hospital care.
AB  - OBJECTIVE: The public, providers and policy-makers are interested in a service
      continuum where care is provided in the appropriate place. Alternate level of
      care is used to define patients who no longer need acute care but remain in an
      acute care bed. Our aims were to determine how subacute care and convalescent
      care should be defined in British Columbia (BC); how these care levels should be
      aligned with existing legislation to provide more consistent service standards to
      patients and what reporting requirements were needed for system planning and
      performance management. METHOD: A literature review was conducted to understand
      the international trends in performance management, care delivery models and
      change management. A Canada-wide survey was carried out to determine the
      directions of other provinces on the defined issues and a BC survey provided a
      current state analysis of programming within the five regional health authorities
      (HAs). RESULTS: A provincial policy framework for subacute and convalescent care
      has been developed to begin to address the concerns raised and provide a base for
      performance measurement. The policy has been approved and disseminated to BC HAs
      for implementation. An implementation plan has been developed and implementation
      activities have been integrated into the work of existing provincial committees.
      Evaluation will occur through performance measurement. The benefits anticipated
      include: clear policy guidance for programme development; improved comparability
      of performance information for system monitoring, planning and integrity of the
      national acute care Discharge Abstracting Database; improved efficiency in acute
      care bed use; and improved equity of access, insurability and quality for
      patients requiring subacute and convalescent care. While a national reporting
      system exists for acute care in Canada, this project raises questions about the
      implications for this system, given the shifting definition of acute care as
      other care levels emerge. Questions are also raised by the finding in Australia
      that the current case-mix system is inadequate to describe these patients.
      Further, given the inadequacy of our understanding of health system capacity and
      output, consideration of a more comprehensive national reporting system along the
      care continuum may be warranted. CONCLUSIONS: This project is an example of
      effective collaboration between the provincial government, a national
      organization and HAs, and suggests that provincial governments can participate in
      a meaningful way to accomplish research-informed health services policy.

PMID- 18325167
TI  - Advancing employee engagement through a healthy workplace strategy.
AB  - BACKGROUND: In recent years, there has been increased focus on improving the
      quality of the working lives of staff in health care organizations. Research
      shows that improvements can be achieved through a comprehensive organizational
      approach to workplace health. Improved worker engagement is a realizable outcome
      of such an approach, provided that it is based on reliable and relevant data and
      is tailored to the specific environment in which it is being implemented.
      ASSESSMENT OF PROBLEM: An intervention project was designed to develop an
      organization-wide approach to employee workplace health. A comprehensive health
      risk assessment was undertaken, along with a staff survey on workplace culture,
      individual health practice and environmental effects on physical health. RESULTS:
      In general, the findings present a positive picture of the culture and factors
      that influence psychological wellbeing. However, improvement is needed in some
      areas: satisfaction is only marginally outweighing stress, and musculoskeletal
      disorders account for much absenteeism. Employee health needs include weight
      management, improving fitness and nutrition, and decreasing coronary risk.
      STRATEGIES FOR CHANGE: Results have prompted this organization to pursue the
      development of a Healthy Workplace Policy that will be used as a filter for all
      other policies relating to workplace culture, environment and practice, and have
      provided the impetus and focus to review the organization of employee health
      services. LESSONS LEARNED: Three major administrative activities are necessary to
      move from planning to sustained action: ensure adherence of all staff to any
      policy derived from a health risk assessment; ensure staff feel proposed changes
      are relevant and important; and create a road map to guide the development of a
      strategic and an implementation plan. The findings outlined in this report can be
      addressed by organizations that are willing to commit to a comprehensive approach
      to workplace health.

PMID- 18325168
TI  - Introducing priority setting and resource allocation in home and community care
      programs.
AB  - OBJECTIVE: To use evidence from research to identify and implement priority
      setting and resource allocation that incorporates both ethical practices and
      economic principles. METHOD: Program budgeting and marginal analysis (PBMA) is
      based on two key economic principles: opportunity cost (i.e. doing one thing
      instead of another) and the margin (i.e. resource allocation should result in
      maximum benefit for available resources). An ethical framework for priority
      setting and resource allocation known as Accountability for Reasonableness (A4R)
      focuses on making sure that resource allocations are based on a fair decision
      making process. It includes the following four conditions: publicity; relevance;
      appeals; and enforcement. More recent literature on the topic suggests that a
      fifth condition, that of empowerment, should be added to the Framework. The 2007
      08 operating budget for Home and Community Care, excluding the residential
      sector, was developed using PBMA and incorporating the A4R conditions. RESULTS:
      Recommendations developed using PBMA were forwarded to the Executive Committee,
      approved and implemented for the 2007-08 fiscal year operating budget. In
      addition there were two projects approved for approximately $200,000. CONCLUSION:
      PBMA is an improvement over previous practice. Managers of Home and Community
      Care are committed to using the process for the 2008-09 fiscal year operating
      budget and expanding its use to include mental health and addictions services. In
      addition, managers of public health prevention and promotion services are
      considering using the process.

PMID- 18325169
TI  - Facilitating organizational mergers: amalgamation of community care access
      centres.
AB  - BACKGROUND: The development of 14 Local Health Integration Networks (LHINs) in
      Ontario necessitated the re-organization of Community Care Access Centres
      (CCACs). The achievement of LHIN objectives was contingent upon the organizations
      responsible for home and long-term care placement being aligned within the LHIN
      geographic boundaries. This re-alignment required 42 provincial organizations to
      re-structure, integrate and reduce to 14. ASSESSMENT OF PROBLEM: This project was
      focused on the amalgamation of two CCACs in the Waterloo Wellington LHIN. Both
      were distinctly different due to their organizational evolution, the composition
      of the region and leadership approach. The different organizational cultures, if
      not managed properly, could result in a derailing of several current projects
      that were underway and were also key to the overall health system transformation
      agenda. A literature search provided a plethora of critiques of organizational
      change approaches and practical suggestions. Of particular relevance was a report
      to the Royal Commission on Health Care in 2002 that authenticates the dismal
      success in health care to meet change objectives. The project included a joint
      planning day for the leadership teams of the two organizations followed by an
      Organizational Readiness Assessment conducted by the Canadian Council on Health
      Services Accreditation (CCHSA). RESULTS: Both activities brought the leadership
      and staff of Waterloo and Wellington together, started the integration process
      and solicited staff participation. A follow-up survey of the leadership teams
      revealed the effectiveness of the project in advancing integration between the
      two organizations and recognizing organizational cultural differences. The CCHSA
      Organizational Readiness Assessment process was viewed as an effective means for
      advancing the integration of the two organizations, particularly as it relates to
      allowing the staff groups to define for themselves the benefits of the merger.
      LESSONS AND MESSAGES: The lack of hard evidence on the benefits of a merger could
      have been problematic in terms of resistance to change if the CCHSA process had
      not been used. The readiness assessment report provided 49 recommendations that
      served as baseline information needed for the design of a change strategy that is
      anchored in knowledge of variation in organizational culture, practice,
      communications, client service and leadership style.

PMID- 18325170
TI  - Increasing the involvement of specialist physicians in chronic disease
      management.
AB  - BACKGROUND: The Capital Health (CH) region in Alberta serves the population of
      the Edmonton area as well as a large referral population in western Canada. CH is
      responsible for the delivery of the spectrum of patient care, from inpatient to
      outpatient services. Growth in outpatient care, in particular, has led to the
      development of several ambulatory care facilities from which the delivery of care
      to several populations with a chronic disease will be coordinated. ASSESSMENT OF
      PROBLEM: The traditional model of care delivery is unsuited to the management of
      chronic diseases. Physicians must be part of the planning and implementation of
      new models if they are to be successful and sustainable. The concept of
      integration into a delivery team is not well understood or practised. This is not
      conducive to the integration of specialist physicians into multidisciplinary
      teams in ambulatory care that serves the needs of patients from a large
      geographic area. RESULTS: Chronic disease management using the Chronic Care Model
      has proven to be an effective method of delivering care to this wide population.
      Specialist physicians have not always taken advantage of opportunities to be
      involved in the planning and development of such new health care projects. In CH,
      physician integration in the planning, development and implementation of this new
      model has proven vital to its success. STRATEGIES FOR CHANGE: We based our
      strategy for change on Wagner's Chronic Care Model. This involved eight steps,
      the first four of which have been completed and the fifth and sixth are underway.
      LESSONS AND MESSAGES: Five factors contributed to the successful integration of
      specialist physicians in chronic disease management: collaboration between
      disciplines and organizations; creating patient-centred services; organizational
      commitments; strong clinical leadership; and early involvement of clinicians.

PMID- 18325171
TI  - Is public health ready for a professional practice framework?
AB  - OBJECTIVE: To develop a framework for professional practice for a large urban
      public health unit in Canada. METHODS: The project involved a literature search,
      key informant interviews, an environmental scan and focus groups. RESULTS:
      Analysis and synthesis led to recommendations for the development of discipline
      specific Professional Practice Leaders (PPL) and an Interprofessional Practice
      Leaders Network. The latter meets to discuss cross-cutting practice issues and is
      chaired by the chief executive officer of the health unit, the Medical Officer of
      Health. The one-year evaluation has demonstrated that this initiative has worked
      well in practice. It is a flexible framework which provides new leadership
      opportunities and gives staff valuable input into decision-making on practice
      issues. It is also a more efficient use of staff resources, including a
      comprehensive approach to solving problems and in breaking down silos between
      programs. Communication and collaboration between disciplines has increased.
      CONCLUSION: The initiative was evaluated successfully after the pilot year. In
      going forward areas to review include the time allotment for the PPL,
      communication between the PPL, the respective Program Director and the entire
      department, and expanding professional development opportunities for the PPL.

PMID- 18325172
TI  - Faecal occult blood tests--eliminate, enhance or update?
AB  - Traditional guaiac-based faecal occult blood tests (FOBT) are commonly performed
      investigations in laboratories, wards, clinics and general practices. Although
      there is much evidence that use of FOBT in asymptomatic population screening
      programmes for colorectal (bowel) cancer does reduce mortality, there is little,
      if any, evidence of the value of FOBT in symptomatic individuals. In contrast,
      recent evidence-based guidelines are unequivocal that most of those presenting
      with symptoms should have bowel visualization and that the only laboratory test
      required is the full blood count. Moreover, recent literature shows that there
      are significant problems in sample collection for FOBT and in analysis of FOBT.
      In view of these facts, it is suggested that FOBT be ceased in all clinical
      settings except in asymptomatic population screening programmes. An alternative
      to elimination of FOBT would be laboratory-led improvement of knowledge on the
      appropriateness of requests, the FOBT used, the quality of FOBT sample collection
      and the standard of analysis, but this would require significant efforts and
      resources, which probably could be better spent elsewhere. A favoured option is
      that FOBT be replaced by faecal immunochemical tests since these undoubtedly have
      many clinical and laboratory advantages and fewer problems in both performance
      and interpretation.

PMID- 18325173
TI  - HDL-cholesterol modulation and its impact on the management of cardiovascular
      risk.
AB  - There is strong epidemiological evidence that HDL-cholesterol (HDL-C) is an
      independent cardiovascular risk factor. A low HDL-C is a common finding in the
      general population, and is a feature of metabolic syndrome, the prevalence of
      which is increasing globally. The importance of HDL-C as a coronary risk factor
      is generally accepted, and has been incorporated into most of the commonly
      applied risk engines. There are several causes of a low HDL-C, including rare
      genetic abnormalities, and more common conditions associated with lifestyle and
      drug therapy. Not all of these are associated with an increased risk of coronary
      disease. A better understanding of HDL metabolism and the mechanisms by which it
      may exert its protective effects has revealed why this may be the case. New
      therapeutic targets have also been identified that may allow HDL-C to be raised
      in patients with low levels. However, good clinical endpoint studies are still
      required to enable the setting of absolute target values for HDL-C in patients at
      high cardiovascular risk.

PMID- 18325174
TI  - The development of a system for the reporting, classification and grading of
      quality failures in the clinical biochemistry laboratory.
AB  - BACKGROUND: There is no agreed system for the reporting, classification and
      grading of the severity of quality failures in the clinical biochemistry
      laboratory. METHODS: A 'Quality Query' reporting system was set up to log all
      quality failures identified by staff and service users. Quality failures were
      classified into three major groups of the preanalytical, analytical and
      postanalytical phases with appropriate subcategories in each group. The severity
      of each quality failure was graded using a five-point scoring system
      incorporating both actual ('A') and potential ('P') score elements. The 'A' score
      measured the actual adverse impact of the quality failure on patient care, while
      the 'P' score measured the 'worst case' potential outcome that might have
      resulted. The system was assessed over a 19-month period. RESULTS: Three hundred
      and ninety-seven Quality Query reports were completed (0.085% of all requests).
      Breakdown by cause: pre-analytical phase--88.9%, analytical phase--9.6%, post
      analytical phase--1.5%. The quality failure severity 'A' scores were skewed
      towards a low adverse impact on patient care: 72.7% allocated an 'A' score of 1
      (least severe grade). The 'P' scores were skewed towards a high potential impact
      on patient care: 65.9% allocated a 'P' score of 5 (most severe grade).
      CONCLUSIONS: The Quality Query reporting system proved easy to integrate into
      routine laboratory practice. Although the great majority of quality failures had
      minimal adverse impact on patient care, the potential for adverse outcomes was
      much higher. This system generates important information on laboratory
      performance and helps inform risk management priorities.

PMID- 18325175
TI  - Audit of internal quality control practice and processes in the south-east of
      England and suggested regional standards.
AB  - BACKGROUND: Internal quality control (IQC) has a long and well-established role
      in clinical biochemistry laboratories. However, despite the duration of use, and
      the publication of several articles detailing best practice, the implementation
      and use of IQC vary significantly between institutions. Consequently, the North
      Thames Audit and Quality Assurance Group undertook a region-wide audit of current
      IQC practice in 2006. METHODS: On aspects of IQC testing, interpretation and
      laboratory processes, 54 laboratories in the region were audited. RESULTS: Audit
      data showed significant variability in all aspects of practice, including IQC
      frequency, use of appropriate material, statistical processing and grades of
      staff involved. CONCLUSIONS: Some of the variation in practice may affect the
      effectiveness of laboratory IQC, and thus the adequacy of a laboratory to monitor
      system performance. Consequently, a set of proposed regional standards have been
      developed and disseminated, prior to re-audit at a future date.

PMID- 18325176
TI  - Measurement of blood glucose: comparison between different types of specimens.
AB  - AIM: To provide conversion formulae between measurements based on different
      specimens in use in epidemiological studies and clinical practice, and to
      evaluate the relative precision for the different methods. BACKGROUND: The
      current guidelines emphasize the use of venous plasma for determining glucose
      concentration. Nevertheless, the World Health Organization (WHO) guidelines
      provide cut-off points for different specimens for the determination of the
      glucose concentration in circulating blood (venous plasma, whole blood, serum and
      capillary blood). There is a lack of data about the comparability between the
      values obtained by using different specimens. METHODS: Eleven different
      combinations of specimens and methods of measurement of blood glucose were used
      in 294 blood samples from 74 subjects. The methods were grouped by the specimen
      used for analysis (venous plasma, whole blood, serum and capillary blood).
      RESULTS: The result of the analysis is a set of linear equations allowing
      conversion of the result from one specimen or method to another. Furthermore, it
      was estimated how much of the variation for each method can be attributed to
      laboratory variance. CONCLUSIONS: Measurements based on capillary blood had a
      very large variability compared with other methods. Measurements based on venous
      whole blood tended to give results 0.5 mmol/L lower than other methods. Our data
      indicate that the current diagnostic cut-off points, as recommended by WHO for
      non-plasma specimens, are not fully compatible and may differ as much as 0.5
      mmol/L between specimens.

PMID- 18325177
TI  - Online extraction of 5-hydroxyindole acetic acid from urine for analysis by
      liquid chromatography-tandem mass spectrometry.
AB  - BACKGROUND: Urinary 5-hydroxyindole acetic acid (5-HIAA) is a useful marker for
      the turnover of tryptophan metabolites in the diagnosis and monitoring of
      carcinoid tumours and the carcinoid syndrome. We have developed a simple and cost
      effective assay for urinary 5-HIAA using liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) incorporating an online sample clean-up process to
      replace a liquid chromatography electrochemical (LC-EC) technique. METHODS:
      Acidified urine was serially diluted in ammonium acetate buffer followed by
      ammonium acetate buffer enriched with 5-hydroxyindole-3-acetic-2,2-D2 acid
      internal standard. A 2.1 x 10 mm C18 column was used for primary online clean-up
      and eluted with 100% methanolic mobile phase onto a second dC18 Atlantis 2.1 x 20
      mm column. Analytes were detected by mass spectrometry using transitions 192.1 >
      146.3 and 194.1 > 148.0 for 5-HIAA and deuterated analyte, respectively. RESULTS:
      Run time was 3 min with 5-HIAA eluting at 1.37 min. The inter and intra-assay
      imprecision and accuracies of the three levels of inhouse quality control (QC)
      (30, 300 and 600 micromol/L) were acceptable with coefficient of variations (CVs)
      and deviation from target values <12% (n = 15). The average recovery of 5-HIAA
      spiked into urine was 93.7% with no ion suppression observed. The limit of
      detection was 2.8 and lower limit of quantification 4.0 micromol/L. Passing
      Bablok regression of LC-EC with LC-MS/MS results showed good agreement between
      the methods, the relationship described as LC-MS/MS = 1.01(LC-EC)-1.22. No
      systematic or proportional biases were observed over the working range of the
      method. The assay was linear to at least 2000 micromol/L. CONCLUSIONS: We have
      developed a robust method offering a more than six-fold improvement in linearity
      compared to the existing LC-EC method.

PMID- 18325178
TI  - Accuracy and clinical implications of seven 25-hydroxyvitamin D methods compared
      with liquid chromatography-tandem mass spectrometry as a reference.
AB  - BACKGROUND: The most reliable assessment of vitamin D status is measurement of
      plasma 25-hydroxyvitamin D (25[OH]D) concentration. High variability in 25(OH)D
      measurements due to utilized test and assay technologies and the lack of
      standardization against reference materials and reference method often confounds
      proper assessment of vitamin D status. METHODS: We evaluated the accuracy of six
      routinely available methodologies: high-performance liquid chromatography (HPLC),
      the IDS-radioimmunoassay (IDS-RIA) and enzyme immunoassay (IDS-EIA), the Nichols
      Advantage automated protein-binding assay (Advantage), two versions of the
      DiaSorin automated immunoassay (Liaison 1 and Liaison 2)--and one prototype
      automated immunoassay (Elecsys) for assessment of the 25(OH)D(3) status in a
      cohort of 300 randomly selected patients' samples compared with the reference
      method liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS:
      Passing-Bablok regression analysis demonstrated a slope for each method compared
      with LC-MS/MS that varied from 0.62 (IDS-EIA) to 1.0 (HPLC). The Advantage and
      the Liaison 1 showed significant deviation from linearity with highly variable
      individual results vs. the LC-MS/MS. Difference plots revealed a considerable
      persistent proportional bias for the IDS-RIA and IDS-EIA. All evaluated methods
      except HPLC demonstrated a more or less considerable deviation of individual
      25(OH)D(3) values compared with LC-MS/MS defined target concentrations.
      CONCLUSIONS: Standardization of methods for the quantification of 25(OH)D on a
      human-based sample panel by means of LCMS/MS would help to reduce the inter
      method variability with respect to accuracy existing in 25(OH)D measurement
      considerably. However, there will still remain differences in the accuracy of
      methods utilizing sample purification before final quantification or
      immunological reaction when compared with those methods without separate sample
      purification.

PMID- 18325179
TI  - Production and certification of four frozen human serum certified reference
      materials containing creatinine and electrolytes.
AB  - BACKGROUND: This paper describes the preparation, analysis and certification of
      four frozen human serum certified reference materials (CRMs) containing
      creatinine and the electrolytes calcium, lithium, magnesium, potassium and
      sodium. These materials have been prepared to give concentrations of these
      analytes that cover the currently accepted analytical range. METHODS: The
      analysis of the materials for certification purposes has been carried out using
      methodology traceable to primary standards, and which is acceptable as a
      reference method. The certification methods include liquid chromatography-mass
      spectrometry (LC-MS) with exact-matching isotope dilution calibration (EM-IDMS)
      for creatinine, inductively-coupled plasma optical emission spectroscopy (ICP
      OES), ICP-MS and isotope-dilution inductively-coupled plasma mass spectroscopy
      (ID-ICP-MS) for the electrolytes. RESULTS: The uncertainties estimated for these
      certified values include a component from the characterization measurements, as
      well as contributions from possible inhomogeneity and long-term instability. The
      certified values have been corroborated by measurements obtained in a major UK
      External Quality Assessment scheme, which have, with the exception of the
      determination of creatinine at a particularly low concentration, given excellent
      agreement. CONCLUSIONS: The materials are intended for use by pathology
      laboratories and manufacturers of in vitro diagnostic (IVD) kits for validation
      of existing routine methodology to a traceable standard, which will promote
      harmonization between the different methods, instruments and IVD kits used in
      these laboratories.

PMID- 18325180
TI  - Intraindividual variation in serum thyroid hormones, parathyroid hormone and
      insulin-like growth factor-1.
AB  - BACKGROUND: Biological variation of an analyte is an important determinant of its
      usefulness. Intraindividual variation in serum thyroid hormones, parathyroid
      hormone (PTH) and insulin-like growth factor-1 (IGF-1) in healthy subjects was
      determined in this study. METHODS: Blood samples were taken at weekly intervals
      for six weeks from 10 healthy subjects and analysed for serum thyroid-stimulating
      hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), PTH and IGF-1.
      RESULTS: Intraindividual variations for serum FT4 and FT3 were <5.0%, IGF-1 9.4%
      and TSH and PTH 25.1% and 25.9%, respectively. Index of individuality was lowest
      for FT4 (0.42) and FT3 (0.38), and highest for PTH (1.09). CONCLUSION:
      Intraindividual variation for FT4, FT3 and IGF-1 are low.

PMID- 18325181
TI  - High-resolution melting analysis for detection of familial ligand-defective
      apolipoprotein B-100 mutations.
AB  - BACKGROUND: Familial ligand-defective apolipoprotein B-100 (FDB) is characterized
      by elevated plasma concentrations of LDL-cholesterol and apolipoprotein (apo) B,
      normal triglyceride and HDL-cholesterol levels, the presence of tendon xanthomas,
      and premature coronary artery disease. FDB cannot be clinically distinguished
      from heterozygous LDL-receptor-defective familial hypercholesterolaemia (FH)
      without genetic testing. METHODS: Amplicons in exon 26 and exon 29 of the APOB
      gene were screened for established genetic variants including mutations and
      polymorphisms using high-resolution melting analysis. Six novel variants
      associated with FDB in hypercholesterolaemic Dutch patients (S3476L, S3488G,
      Y3533C, T3540M, I4350T, G4368D) were also studied. RESULTS: All positive
      controls, a total of 10 mutations in exon 26 and four mutations in exon 29, were
      readily detectable by melting curve analysis. In addition, a patient previously
      not known to be heterozygous for the H3543Y mutation was identified in a screen
      of hypercholesterolaemic subjects. The method was validated by comparison of high
      resolution melting analysis with DNA sequence data in a 'blinded' manner in 35
      consecutive patients attending a lipid disorders clinic. These patients were
      classified as 'definite FH' by the Dutch Lipid Clinic Network criteria. Five
      patients were found to be heterozygous for the R3500Q and one for H3543Y.
      CONCLUSIONS: We have established a novel, robust method of FDB mutation detection
      using high-resolution melting analysis in conjunction with DNA sequencing.
      Compared with existing methods it is not only more cost-effective, but is also
      capable of detecting new sequence changes and will have importance in cascade
      screening of affected subjects.

PMID- 18325182
TI  - Automated assay for plasma D-lactate by enzymatic spectrophotometric analysis
      with sample blank correction.
AB  - BACKGROUND: D-lactate is essentially a product of bacterial metabolism, and its
      assessment in plasma has been mainly used to diagnose D-lactic acidosis in
      patients with short bowel syndrome. In the last few years, there has been growing
      interest in the use of subclinical elevations of D-lactate concentrations as a
      diagnostic tool in a variety of clinical conditions such as ischaemia, trauma or
      infection. METHODS: An endpoint enzymatic spectrophotometric assay to measure
      plasma D-lactate with a sample blank correction was validated on our routine
      clinical chemistry analyser (Olympus AU640). An ultrafiltration procedure was
      used in samples with a high L-lactate dehydrogenase (L-LDH) activity in order to
      avoid underestimation of the D-lactate concentration, when a sample blank was
      processed. RESULTS: The intra- and inter-assay imprecision were <5.1% and <13.3%,
      respectively and the mean recovery for the D-lactate assay was 95% (range 88
      103%). Samples with L-LDH activity greater than 1500 IU/L required the use of
      ultrafiltration devices. Plasma D-lactate concentration in our 'non-diseased'
      paediatric population showed a non-Gaussian distribution--95th percentile equal
      to 19 micromol/L--and no difference based on gender or age was observed.
      CONCLUSION: We have established an accurate, sensitive and precise routine assay
      for D-lactate measurement in plasma. The assay was used to formulate paediatric
      reference ranges and will be used to assist clinicians to evaluate 'D-lactate
      toxicity' in patients with a variety of conditions such as short bowel syndrome,
      small bowel transplantation and as an early marker of intestinal ischaemia.

PMID- 18325183
TI  - Cardiac troponin I measurement using the ACS:180 to predict four-year cardiac
      event rate.
AB  - BACKGROUND: This study aimed at evaluating the ability of cardiac troponin I
      (cTnI) measurement on the ACS:180 for prognostic risk stratification. Sequential
      admissions to the coronary care unit of a busy district general hospital were
      studied. All patients were followed up for a maximum of 4.3 years and cardiac
      events, either cardiac death, readmission with acute myocardial infarction or
      admission with acute unstable angina were documented. METHODS: Blood samples were
      taken on admission and at 4 and 12 h. A serum aliquot was taken and stored frozen
      at -70 degrees C. The frozen aliquots were subsequently analysed for cTnI by
      chemiluminescent immunoassay using an ACS:180. Patients were categorized into
      those with or without ST segment elevation on the presenting electrocardiogram.
      The optimized decision threshold for mortality and event prediction was then
      determined by log-rank analysis and by construction of Kaplan-Meier survival
      plots. RESULTS: A total of 289 patients (196 men) median age 65.3 years, range
      27.4-87.9 years were studied. Out of this, 139 had ST elevation myocardial
      infarction (STEMI) and 150 had suspected non-STEMI (NSTEMI). Full data were
      available from 278 patients. Admission cTnI did not predict any of the endpoints
      in the STEMI group. In patients admitted with suspected NSTEMI, admission and
      peak cTnI predicted increased risk of death or readmission with acute myocardial
      infarction. In addition, peak cTnI predicted increased risk of death. CONCLUSION:
      A cTnI exceeding 0.16 microg/L on admission or during hospital stay predicted an
      increased cardiac event rate at four years in patients admitted with suspected
      NSTEMI.

PMID- 18325184
TI  - What is the role of cerebrospinal fluid ferritin in the diagnosis of subarachnoid
      haemorrhage in computed tomography-negative patients?
AB  - BACKGROUND: Spectrophotometry of cerebrospinal fluid (CSF) for bilirubin is the
      recommended method for investigation in suspected cases of subarachnoid
      haemorrhage (SAH), when a computed tomography (CT) of the head is negative for
      blood. There is a potential need for a simpler alternative. Measurement of CSF
      ferritin might fulfil this need. METHOD: We have measured ferritin in the CSF
      from 252 patients with suspected SAH who were negative on a CT of the head for
      blood, recruited on a consecutive intention to recruit basis from four centres.
      CSF spectrophotometry was performed on all samples. A positive outcome was taken
      as an aneurysm found on angiography that was treated or a discharge diagnosis of
      non-aneurysmal SAH. RESULTS: A final diagnosis of aneurysmal SAH was made in six
      patients, an arteriovenous malformation in one and non-aneurysmal SAH in nine.
      Receiver operating characteristic (ROC) analysis showed that at 6.4 microg/L,
      sensitivity, specificity, positive and negative predictive values were 1.0, 0.48,
      0.12 and 1.0, respectively. At 12 microg/L, these values were 0.81, 0.91, 0.38
      and 0.98, respectively. CONCLUSIONS: At an appropriate negative predictive value
      (1.0) for a rule-out test, ferritin has too low a specificity to function as a
      stand-alone test and we cannot recommend it as an initial screen to be followed
      by spectrophotometry.

PMID- 18325185
TI  - Hyperhomocysteinaemia and parameters of antioxidative defence in Tunisian
      patients with coronary heart disease.
AB  - BACKGROUND: An imbalance between oxidative damage and antioxidative protection in
      association with the pathophysiology of atherosclerosis has been suggested. The
      aim of this study was to test the parameters of antioxidative defence and to
      assess their association with hyperhomocysteinaemia and the severity of coronary
      heart disease (CHD) in Tunisian patients. METHODS: The study population included
      100 patients with CHD and 120 healthy controls. The severity of CHD was expressed
      as the number of affected vessels. Superoxide dismutase (SOD) activity,
      glutathione peroxidase (GPx) activity and total antioxidant status (TAS)
      concentrations were measured using commercially available methods. Plasma total
      homocysteine (tHcy) concentration was determined by direct chemiluminescence
      assay. Serum zinc (Zn) was measured by a colorimetric method. RESULTS: Compared
      with healthy control subjects, patients with CHD had significantly lower
      activities of SOD (P < 0.01), GPx (P < 0.001), and serum Zn concentrations (P <
      0.001) and significantly higher tHcy concentration (P < 0.001). However TAS
      concentrations were not significantly different between the groups. SOD and GPx
      activities were negatively correlated with tHcy concentration (P < 0.05, P <
      0.001, respectively). Patients with hyperhomocysteinaemia showed a lower GPx and
      SOD activities than patients with normohomocysteinaemia. Antioxidant enzyme
      activities tended to be decreased in CHD patients presenting with 0- to 3-vessel
      stenosis. CONCLUSIONS: This study indicates that low activity of GPx, SOD and Zn
      concentration are associated with CHD patients. We hypothesize that
      hyperhomocysteinaemia and low antioxidant enzyme activities may increase the
      extent of CHD.

PMID- 18325186
TI  - Are patients with familial hypercholesterolaemia well managed in lipid clinics?
      An audit of eleven clinics from the Department of Health Familial
      Hypercholesterolaemia Cascade Testing project.
AB  - BACKGROUND: Familial hypercholesterolaemia (FH) is an autosomal co-dominant
      disorder which is relatively common, leads to high levels of LDL-cholesterol and
      if untreated to early coronary heart disease. An audit of current practice at
      National Health Service Trusts in England was undertaken to determine whether FH
      patients meet the diagnostic criteria for FH; are being offered appropriate
      advice and treatment; and to what extent their families are contacted and offered
      testing for the disorder. METHODS: Medical records of known FH patients (over 18
      years of age and diagnosed before 31 December 2003) were accessed to obtain
      information on diagnosis, treatment and family tracing. RESULTS: The records of
      733 FH patients were examined, 79% met the UK 'Simon Broome' register criteria
      for the diagnosis of definite or possible FH. Analyses showed that patients were
      usually offered appropriate advice and treatment, with 89% being on a statin.
      However, the audit indicated a high variability in family tracing between the
      sites, with significant differences in the frequency of inclusion of a family
      pedigree in the notes (range 1-71%, mean 35%); the general practitioner (GP)
      being advised that first-degree relatives should be tested (range 4-52%, mean
      27%); and the proportion of relatives contacted and tested (range 6-50%, mean
      32%). CONCLUSION: FH patients are well cared for in lipid clinics in England, are
      being given appropriate lifestyle advice and medication, but an increase in
      recording of LDL-cholesterol levels may lead to improvements in their management.
      Practice in family tracing appears to vary widely between clinics.

PMID- 18325187
TI  - Adverse metabolic profiles in a cohort of obese Irish children.
AB  - BACKGROUND: The metabolic characteristics of obese Irish children are not well
      defined. We prospectively examined the relationship between the degree of obesity
      and glucose metabolism, insulin sensitivity and suspected non-alcoholic
      steatohepatosis (NASH) in a pilot study of obese Irish children. METHODS: We
      measured height, weight, body mass index (BMI), blood pressure, waist and hip
      circumference in 18 participants (mean age 15.5 years). Fasting blood glucose,
      insulin, lipid profile and alanine aminotransferase (ALT) concentrations were
      also measured. A standard 75 g oral glucose tolerance test was performed and
      insulin sensitivity was derived from this using a mathematical model--oral
      glucose insulin sensitivity. RESULTS: There were significant associations between
      the degree of obesity, insulin sensitivity and markers of liver steatosis. For
      example, when adjusted for pubertal status, there were significant associations
      between standardized BMI and insulin sensitivity (regression coefficient, beta = 
      70.1, P = 0.018) and ALT (beta = 20.7, P = 0.007). CONCLUSION: This study
      suggests that the degree of obesity is associated with lower insulin sensitivity
      and possible NASH in obese Irish children.

PMID- 18325188
TI  - Naturally occurring isotopes of an analyte can interfere with doubly deuterated
      internal standard measurement.
AB  - BACKGROUND: Internal standards are essential in quantitative mass spectrometry
      (MS) assays to correct for variability in sample extraction and ionization at the
      source. In liquid chromatography MS assays, analogues of the analyte with several
      atoms replaced by their stable isotopes, e.g. (2)H (D, deuterium) are often used
      as internal standards. METHODS: Possible interference by naturally occurring
      isotopes of an analyte in the internal standard channel in a liquid
      chromatography tandem MS assay was assessed using cortisol and its deuterated
      internal standard, D2-cortisol, as an example. Mass spectra were analysed and
      standard curves were prepared with varying concentrations of internal standard to
      determine the extent of any interference. RESULTS: The mass spectra showed that a
      naturally occurring isotope of cortisol at m/z 365 acts in the same way as D2
      cortisol and fragments to give a daughter ion of the same m/z. Cortisol-365 can
      therefore falsely, but significantly, increase the amount of internal standard
      detected, and this will concomitantly decrease the relative response for
      cortisol. The standard curves with varying concentrations of internal standard
      showed that this phenomenon can affect the linearity of an assay. CONCLUSIONS:
      Our results show that care is needed in assay development when doubly deuterated
      internal standards are used. Interference by naturally occurring isotopes of the
      analyte of interest in the internal standard transition is possible and it is
      important to ensure that an appropriate internal standard concentration is chosen
      that permits linearity of the assay over the required range.

PMID- 18325189
TI  - Balance of transforming growth factor-beta1 and platelet-derived growth factor-BB
      is associated with kidney allograft rejection.
AB  - BACKGROUND: About 50% of kidney-transplant patients undergo organ rejection
      within 10 years. Chronic allograft nephropathy (CAN) represents the dominant
      cause of kidney transplant failure and accounts for 50-80% of graft loss in long
      term surviving patients. CAN pathogenesis is multifactorial and not-completely
      elucidated; several reports indicate TGF-beta1 and platelet-derived growth factor
      (PDGF)-BB expression in CAN suggesting a possible role of these factors in the
      allograft arteriosclerosis and graft failure. METHODS: We investigated the plasma
      expression concentrations of human growth factors with enzyme-linked
      immunosorbent assays and appropriate statistical analysis. RESULTS: We present
      evidences showing statistically significant association of CAN with a specific
      balance between TGF Beat1 and PDGF-BB plasma concentrations, in 129 kidney
      transplant patients and 15 healthy controls. Odds ratios were computed to
      correlate expression-levels with CAN occurrence. CONCLUSION: We believe these
      data may suggest a novel non-invasive method to identify early molecular markers
      of graft deterioration.

PMID- 18325190
TI  - An apparent phaeochromocytoma and abnormal thyroid function tests.
AB  - A 41-year-old lady presented with classical symptoms of a phaeochromocytoma and
      markedly elevated urinary adrenaline concentration. Urinary fractionated
      metanephrine and normetanephrine concentrations were within the normal reference
      range. Computed tomography of the abdomen/pelvis and I(123) meta
      iodobenzylguanidine scans were negative. Factitious adrenaline use was
      established as the diagnosis.

PMID- 18325191
TI  - Thyrotoxic periodic paralysis in an Italian man: clinical manifestation and
      genetic analysis.
AB  - In Western countries, thyrotoxic periodic paralysis (TPP) is a rare condition
      with only sporadic cases described so far. Here, we describe a 29-year-old
      Italian man who presented with leg weakness and hypokalaemia. Treatment with
      intravenous potassium resulted in a rapid resolution of symptoms. TPP as the
      underlying cause was suggested by suppressed thyroid-stimulating hormone (TSH),
      elevated free T3 and free T4, and the presence of TSH-receptor antibodies (TRAB).
      Genetic analysis showed no mutations in the candidate exons of calcium (CACN1AS),
      potassium (KCNE3) and sodium (SCN4A) channel genes. However, we identified the
      presence of two single nucleotide polymorphisms (SNPs), 1491C > T and 1551 T > C,
      in exon 11 of the CACN1AS gene. Although the 1491C > T SNP is not apparently
      involved in the pathogenesis of the disease, the 1551 T > C SNP has been
      associated with TPP in Asians and reported in only one case in European
      Caucasians. Further investigations are needed to clarify whether such
      polymorphisms have a role in the disease pathogenesis in Caucasians.

PMID- 18325192
TI  - Hypokalaemic paralysis precipitated by distal renal tubular acidosis secondary to
      Sjogren's syndrome.
AB  - A 43-year-old woman presented with a sudden onset of hypokalaemic paralysis
      requiring intubation and ventilatory support. Subsequent biochemical and clinical
      assessments established a diagnosis of distal renal tubular acidosis (RTA) in
      association with underlying Sjogren's syndrome as the aetiology of her profound
      hypokalaemia. Distal RTA is rare, but Sjogren's syndrome is one of the more
      common causes in adults and should be considered in the differential diagnosis of
      patients who present with hypokalaemic muscular paralysis.

PMID- 18325193
TI  - Within-subject biological variation in disease: the case of tumour markers.

PMID- 18325197
TI  - Thoracoscopic excision of mediastinal parathyroid adenomas: a report of two
      cases.
AB  - Two patients with primary hyperparathyroidism caused by solitary ectopic
      mediastinal parathyroid adenomas have been successfully treated by thoracoscopic
      excision. The patients were not suitable for open thoracic surgery. Both had
      right-sided adenomas confirmed by sestamibi and computerised tomography - one
      adjacent to the oesophagus at the level of D3, the other anterolateral to the
      ascending aorta. Both procedures were performed through one 12-mm camera port and
      two 5-mm operating ports, and were uncomplicated, with 30-45 minutes skin-to-skin
      operating time. Both patients were well enough to be discharged the next day, and
      both rapidly became normocalcaemic. At follow-up, neither had developed any
      complications. In selected cases, where an ectopic adenoma lies immediately deep
      to the mediastinal pleura, thoracoscopic excision offers considerable advantage
      over open thoracic surgery.

PMID- 18325198
TI  - A pressing diagnosis - a compromised testicle secondary to compartment syndrome.
AB  - Hydrocoeles are a common cause of scrotal swelling and discomfort in a
      significant proportion of men. We report a case of compartment syndrome within
      the tunica vaginalis. This is an unusual and previously unreported complication
      of a hydrocoele.

PMID- 18325199
TI  - Turner syndrome - an accidental finding?
AB  - We report the case of a 9-year-old girl with bilaterally reduced pedal pulses
      following emergency surgery for unilateral subtrochanteric femoral fracture. This
      incidental postoperative finding of differential blood pressures between the
      upper and lower limbs led to the diagnosis of aortic coarctation and subsequent
      karyotype analysis confirmed the rare diagnosis of Turner syndrome.

PMID- 18325200
TI  - Conservative management of pneumatosis intestinalis and massive pneumoperitoneum
      in the acute abdomen: a case report.
AB  - We present a case of massive pneumoperitoneum in association with pneumatosis
      intestinalis that was successfully managed without surgery despite a clinical
      picture of an acute abdomen and biochemical evidence of inflammation and systemic
      upset. Recognition of non-surgical pneumoperitoneum is important to avoid
      unnecessary laparotomy, and clinical examination for the presence of peritonitis
      is the most important determinant of the need for emergency surgery.

PMID- 18325201
TI  - Extensor tendon injury to the index and middle finger secondary to Kirschner wire
      insertion for a distal radial fracture.
AB  - We describe a case with the highly unusual complication of attritional ruptures
      to both the extensor tendons to the index and middle finger following Kirschner
      wire placements for a distal radial fracture. This particular complication has
      never been previously described in the literature. We also review the literature,
      identifying certain techniques in the management of distal radial fractures with
      Kirschner wires which are considered to increase the risk of tendonous or
      neurovascular injury. Finally, recommendations are made that should reduce the
      complications of iatrogenic soft tissue injury associated with this very common
      procedure.

PMID- 18325202
TI  - The impact of Creutzfeldt-Jakob disease on surgical practice.
AB  - Creutzfeldt-Jakob disease (CJD) is characterised by abnormal prion protein that
      can replicate and replace nervous tissue, with rapid lethal neurodegenerative
      consequences. The transmissible nature of CJD has been known for half a century
      and transmission has occurred through neurosurgical procedures. Variant
      Creutzfeldt-Jakob disease (vCJD) emerged in 1996, and the presence of abnormal
      prion in lymphatic tissue extended the number of surgical specialties dealing
      with infected material; transmission through blood transfusion raised the
      possibilities of a large carrier pool and spread of epidemic proportion. The
      abnormal prion is difficult to remove and this could influence future
      decontamination programmes. Contaminated instruments must be withdrawn from
      surgical practice, and this can interfere with the efficient running of a
      surgical unit and optimal patient care. There is an urgent need for reliable
      methods for the detection of abnormal prion, within and outside the body. These
      will help to clarify the epidemiology of CJD, and to reduce its transmission via
      blood and tissue. They will also allow determination of the efficacy of new
      decontamination products in surgical practice, and the value of any treatment of
      sufferers and carriers of CJD. In the meantime, continued vigilance and informed
      regulation of all aspects of CJD must remain.

PMID- 18325203
TI  - Vascular surgical training.

PMID- 18325204
TI  - Future of vascular surgical training: the trainees' views.
AB  - INTRODUCTION: In the UK, surgical training includes all aspects of general
      surgery. Vascular surgery is not an independent specialty. We wished to assess
      the views of vascular trainees in UK on the future of vascular surgery and
      training. MATERIALS AND METHODS: Trainees were surveyed in 2003, 2004 (after
      introduction of the European Working Time Directive) and 2005, concentrating on
      four areas - future practise of vascular surgery, role of endovascular training,
      vascular specialisation and future training. RESULTS: The majority of trainees
      want to practise vascular surgery alone. In 2003, 80% thought training should
      include endovascular techniques. By 2005, all trainees regarded training as
      mandatory as endovascular techniques would represent a significant part of their
      future work. Opinion changed on training; from 4 years general then 2 years
      vascular surgery (qualification in general surgery) to 2 years general and 4
      years vascular surgery (specialist qualification in vascular surgery; P <
      0.0001). Opinion also changed, that vascular surgery should spilt from general
      surgery to form its own speciality (P < 0.0007). CONCLUSIONS: Trainees now regard
      training in endovascular techniques and endovascular aneurysm repair as
      mandatory. The majority wish to specialise from general surgery and achieve a
      separate qualification in vascular surgery.

PMID- 18325205
TI  - Should vascular surgeons be trained in endovascular techniques? An observational
      study.
AB  - INTRODUCTION: The aim of this study was to determine if there is a satisfactory
      cover for interventional radiology and whether vascular surgeons have received
      sufficient training in endovascular techniques. MATERIALS AND METHODS: This was
      an observational study based on questionnaires sent to radiology and vascular
      trainers and vascular trainees in England. A total of 50 NHS trusts were chosen
      randomly to take part in the study and 320 questionnaires were sent out with an
      overall consultant response rate of 57%. RESULTS: Of vascular consultants in the
      study group, 53% have had experience in endovascular procedures. Overall, 87%
      felt that there were not enough radiologists to fulfil the demand and 64% would
      like further training in endovascular procedures. In addition, 69% would like to
      be involved in a vascular rota without the general component. Similarly, 81% of
      radiologists felt that the demand was not being met, as emergency interventional
      radiology cover was not available on most nights in 65% of the trusts. Of
      responders, 72% would not object to training of vascular trainees in
      interventional work and 43% would be happy to be involved in training. Some 33%
      would accept a vascular trainee for 1 year. CONCLUSIONS: Integrated fellowship in
      vascular surgery and interventional radiology has been implemented and tested in
      a number of centres in the US. This approach could be implemented in some of the
      larger vascular units in the UK.

PMID- 18325206
TI  - The dedicated emergency surgeon: towards consultant-based acute surgical
      admissions.
AB  - INTRODUCTION: The management of an efficient acute surgical service with
      conflicting pressures of managing elective and emergency work, compounded by
      waiting list targets and the maximum 4-h wait for patients in accident and
      emergency poses a significant challenge. We assess the impact of appointing a
      dedicated emergency surgeon on the delivery of our emergency surgery service.
      PATIENTS AND METHODS: A comparative retrospective review was undertaken of all
      surgical admissions (n = 1622) over a 9-month period (between February and
      November) in the year before and after (2004 and 2005) the appointment of a
      dedicated emergency surgeon. The impact on service, training and possible
      financial consequences of this appointment was assessed. RESULTS: A total of 798
      surgical admissions in 2004 were compared with 824 admissions in 2005 for the 9
      month periods of this study. In 2004, 258 patients were operated on compared with
      286 in 2005 (NS). There was a significant increase in day-time operating from 57%
      in 2004 to 74% in 2005 (P < 0.001) and a significant increase in consultant
      supervised operations from 14% to 52% (P < 0.001), with a consequent fall in out
      of-hours operating (43% to 26%; P < 0.001). In addition, there was a significant
      increase in early (within 48 h) discharges from 41% to 53% (P < 0.001). The
      salary of the new appointment is more than offset by the quantifiable savings of
      approximately pound90,000 per annum based on the increased proportion of earlier
      discharges alone as well as the improved quality of care provided. CONCLUSIONS:
      The appointment of a dedicated emergency surgery consultant has resulted in an
      increase in day-time consultant-supervised operating, shorter hospital stay for
      emergency admissions, improved training for surgical trainees, as well as
      providing potential financial savings for the trust.

PMID- 18325207
TI  - Recent changes in the management of blunt splenic injury: effect on splenic
      trauma patients and hospital implications.
AB  - INTRODUCTION: Management of blunt splenic injury has been controversial with an
      increasing trend towards splenic conservation. A retrospective study was
      performed to identify the effect of this changed policy on splenic trauma
      patients and its implications. PATIENTS AND METHODS: Data regarding patient
      demography, mode of splenic injury, CT grading, blood transfusion requirement,
      operative findings hospital stay and follow-up were collected. Statistical
      analysis of the data was performed using nonparametric Mann-Whitney tests
      RESULTS: Over an 8-year period, only 21 patients were admitted with blunt splenic
      injury. Ten patients were managed operatively and 11 non-operatively. Non
      operative management failed in one patient due to continued bleeding. Using
      Buntain's CT grading, the majority of grades I and II splenic injuries were
      managed non-operatively and grades III and IV were managed operatively ( P =
      0.008). Blood transfusion requirement was significantly higher among the
      operative group (P = 0.004) but the non-operative group had a significantly
      longer hospital stay (P = 0.029). Among those managed non-operatively (median
      age, 24.5 years), a number of patients were followed up with CT scans with
      significant radiation exposure and unknown longterm consequences. CONCLUSIONS:
      Non-operative management of blunt splenic trauma in adults can be performed with
      an acceptable outcome. Although CT is classed as the 'gold standard', initial
      imaging for detection and evaluation of blunt splenic injury, ultrasound can play
      a major role in follow-up imaging and potentially avoids major radiation
      exposure.

PMID- 18325208
TI  - Mobile phones, in combination with a computer locator system, improve the
      response times of emergency medical services in central London.
AB  - INTRODUCTION: The aim of this study was to determine whether mobile phones and
      mobile phone locating devices are associated with improved ambulance response
      times in central London. PATIENTS AND METHODS: All calls from the London
      Ambulance Service database since 1999 were analysed. In addition, 100 consecutive
      patients completed a questionnaire on mobile phone use whilst attending the St
      Thomas's Hospital Emergency Department in central London. RESULTS: Mobile phone
      use for emergencies in central London has increased from 4007 (5% of total) calls
      in January 1999 to 21,585 (29%) in August 2004. Ambulance response times for
      mobile phone calls were reduced after the introduction of the mobile phone
      locating system (mean 469 s versus 444 s; P = 0.0195). The proportion of mobile
      phone calls made from mobile phones for life-threatening emergencies was higher
      after injury than for medical emergencies (41% versus 16%, P = 0.0063). Of
      patients transported to the accident and emergency department by ambulance, 44%
      contacted the ambulance service by mobile phone. Three-quarters of calls made
      from outside the home or work-place were by mobile phone and 72% of patients
      indicated that it would have taken longer to contact the emergency services if
      they had not used a mobile. CONCLUSIONS: Since the introduction of the mobile
      phone locating system, there has been an improvement in ambulance response times.
      Mobile locating systems in urban areas across the UK may lead to faster response
      times and, potentially, improved patient outcomes.

PMID- 18325209
TI  - The effectiveness of physiotherapist-led arthroplasty follow-up clinics.
AB  - INTRODUCTION: The conventional job descriptions of professionals within the NHS
      need to evolve in order to meet increasingly stringent targets and demands. One
      innovation is the introduction of a physiotherapist-led arthroplasty follow-up
      clinic. We present an audit of 1000 appointments to this clinic. PATIENTS AND
      METHODS: A total of 865 patients were seen with 933 arthroplasties over an 8
      month period; 135 appointments were not attended. Prospective data were collected
      at each attendance. RESULTS: Less than 7.5% of patients required re-referral to
      an orthopaedic consultant, of which 36% were for consideration for further joint
      replacement. The cost of a physiotherapy appointment was pound4.97 compared to
      pound5.04 for a traditional orthopaedic assessment. By reducing the number of
      follow-up patients seen in orthopaedic clinics, we estimate that each consultant
      would be able to see two additional new patients per week. CONCLUSIONS:
      Assessment of arthroplasty follow-up outside of the traditional orthopaedic
      clinic setting is a time-effective alternative; however, the cost-benefit and
      educational impact is less clear.

PMID- 18325210
TI  - Learning assessment at shoulder surgical skills course.
AB  - INTRODUCTION: Surgical skills courses are an important part of learning during
      surgical training. The assessments at these courses tend to be subjective and
      anecdotal. Objective assessment using multiple choice questions (MCQs) quantifies
      the learning experience for both the organisers and the participants. MATERIALS
      AND METHODS: Participants of the open shoulder surgical skills course conducted
      at The Royal College of Surgeons of England in 2005 and 2006 underwent assessment
      using MCQs prior to and after the course. RESULTS: The participants were grouped
      as non-consultants (14) and consultant orthopaedic surgeons (8). All participants
      improved after attending the course. The average improvement was 17% (range, 4
      43%). We compared the two groups while adjusting for the association between pre
      course score and score gain. We found a strong correlation between pre-course
      score and score gain (r = 0.734; P = 0.001). Adjusted for pre-course score, we
      found that the score gain (learning) for the non-consultants was slightly larger
      than for the consultants, but this did not reach statistical significance (P =
      0.247). CONCLUSIONS: All participants had a positive learning experience which
      did not have a significant correlation to the grade of surgeon.

PMID- 18325211
TI  - D-Dimer in the diagnosis of deep vein thrombosis following total hip and knee
      replacement: a prospective study.
AB  - INTRODUCTION: The merit of using D-dimer estimations in patients following total
      hip and knee replacement has been previously questioned. A survey of radiology
      protocols in 70 hospitals ascertained that the test continues to be mandatory in
      51 prior to formal radiological investigation of suspected deep vein thrombosis
      (DVT) in this patient population. PATIENTS AND METHODS: In this study, D-dimer
      levels were measured pre-operatively and during the first 7 days following
      primary total hip and knee replacement to estimate the range of normal values in
      these patients. RESULTS: All 78 patients were ultrasonographically shown to be
      clear of DVT. D-Dimer levels were significantly raised in all patients at all
      measurements during the first week. Levels after total knee replacement were
      higher than after total hip replacement. Comparison was made with an age-matched
      group who had a proven DVT. There was no difference in D-dimer levels between
      patients with or without a DVT. CONCLUSIONS: The use of this test in this patient
      group is a waste of resource and merely delays appropriate radiological
      investigation and treatment.

PMID- 18325212
TI  - Short-term results of musculotendinous release for paralytic hip subluxation in
      children with spastic cerebral palsy.
AB  - INTRODUCTION: Children with paralytic hip subluxation secondary to spastic
      cerebral palsy were treated with a standard protocol that depended on early
      detection of the subluxation using clinical examination detecting limited range
      of hip abduction of <or= 30 degrees and anteroposterior pelvis radiographs
      detecting subluxation >or= 33% migration as indications. PATIENTS AND METHODS:
      Patients underwent open adductor longus, proximal gracilis and proximal rectus
      femoris myotomy, and iliopsoas lengthening with immediate postoperative
      immobilisation in abduction bar for 3 weeks followed by physiotherapy. The
      protocol was applied to 50 children with a mean age of 3.6 years with 100 hips
      surgically corrected. Of these hips initially, 52% were mildly subluxated with
      <or= 33% migration, 42% were moderately subluxated with > 33-66% migration, and
      6% were severely subluxated with > 66% migration. RESULTS: At a final
      postoperative follow-up of at least 24 months, 22% of these hips were classified
      as excellent with full containment and no migration, 54% were good with < 20%
      migration, and 24% were fair with 20-25% migration. No poor result with > 25%
      migration was obtained. No child developed an abduction contracture or wide-based
      gait that required treatment. CONCLUSIONS: Early detection and application of
      this treatment algorithm for children with spastic hip disease should have
      satisfactory outcomes. Longer follow-up will be required to determine how many
      children will need bony reconstruction to maintain stable containment of hips at
      maturity.

PMID- 18325213
TI  - Wedding rings are not a significant source of bacterial contamination following
      surgical scrubbing.
AB  - INTRODUCTION: Despite some evidence that the wearing of rings may increase the
      microbial load, there is currently nothing to suggest that viable bacteria remain
      following a standard surgical scrub. The aim of the study was to examine the
      distribution and type of microbial flora seen on the hands of doctors following a
      standard surgical scrub. MATERIALS AND METHODS: Ten surgeons and 10
      anaesthetists, all of whom wore wedding rings on the fourth finger of their left
      hand, participated in the study. Each individual was asked to 'scrub-up' as for
      their normal first scrub of the day. Following completion of washing, the wedding
      ring was removed, its internal circumference swabbed and the swab placed in a
      culture medium. Volunteers placed each hand palm-down on separate agar plates.
      The plates were incubated and the number of colonies counted and classified.
      RESULTS: The culture plates of one of the anaesthetists were damaged in transit
      leaving a total of 19 subjects for analysis. In all the palm imprint plates,
      coagulase-negative staphylococci were grown. One surgeon grew coagulase-negative
      staphylococci from the ring swab. A Candida spp. from the right hand of one
      surgeon was grown. There was no statistically significant difference between the
      number of colony-forming units (CFUs) cultured from the right and left (ring
      wearing) hands of the surgeons (P = 0.260) and anaesthetists ( P = 0.345). There
      was no statistical difference in CFUs when surgeons were compared with
      anaesthetists (P = 0.383 for right hand and P = 0.234 for left). CONCLUSIONS:
      This preliminary study would suggest that a traditional band wedding ring is not
      a source of a bacterial load following a standard surgical scrub procedure and,
      as such, there is no requirement for their removal pre-operatively.

PMID- 18325214
TI  - Noise pollution on an acute surgical ward.
AB  - INTRODUCTION: This study was undertaken to measure and analyse noise levels over
      a 24-h period on five general surgical wards. PATIENTS AND METHODS: Noise levels
      were measured on three wards with four bays of six beds each (wards A, B and C),
      one ward of side-rooms only (ward D) and a surgical high dependency unit (ward E)
      of eight beds. Noise levels were measured for 15 min at 4-hourly intervals over a
      period of 24 h midweek. The maximum sound pressure level, baseline sound pressure
      level and the equivalent continuous level (LEq) were recorded. Peak levels and
      LEq were compared with World Health Organization (WHO) guidelines for community
      noise. Control measurements were taken elsewhere in the hospital and at a variety
      of public places for comparison. RESULTS: The highest peak noise level recorded
      was 95.6 dB on ward E, a level comparable to a heavy truck. This exceeded all
      control peak readings except that recorded at the bus stop. Peak readings
      frequently exceeded 80 dB during the day on all wards. Each ward had at least one
      measurement which exceeded the peak sound level of 82.5 dB recorded in the
      supermarket. The highest peak measurements on wards A, B, C and E also exceeded
      peak readings at the hospital main entrance (83.4 dB) and coffee shop (83.4 dB).
      Ward E had the highest mean peak reading during the day and at night - 83.45 dB
      and 81.0 dB, respectively. Ward D, the ward of side-rooms, had the lowest day
      time mean LEq (55.9 dB). Analysis of the LEq results showed that readings on ward
      E were significantly higher than readings on wards A, B and C as a group (P =
      0.001). LEq readings on ward E were also significantly higher than readings on
      ward D (P < 0.001). Day and night levels differ significantly, but least so on
      the high dependency unit. CONCLUSIONS: The WHO guidelines state that noise levels
      on wards should not exceed 30 dB LEq (day and night) and that peak noise levels
      at night should not exceed 40 dB. Our results exceed these guidelines at all
      times. It is likely that these findings will translate to other hospitals. Urgent
      measures are needed to rectify this.

PMID- 18325215
TI  - Audit of referral patterns for hernia repair - are general practitioners aware of
      the changing face of herniorrhaphy?
AB  - INTRODUCTION: The objective of this study was to examine referral patterns from
      general practitioners for groin hernia surgery and to assess their knowledge of
      services available to their patients. PATIENTS AND METHODS: An anonymous postal
      questionnaire was sent to 120 general practitioners (GPs) in the South East Wales
      region who routinely refer patients for inguinal hernia surgery to the Royal
      Gwent Healthcare NHS Trust. RESULTS: A total of 86 questionnaire replies were
      returned. There was variation in referral patterns between the GPs with the
      majority (84%) referring their patients for groin hernia repair to either a
      general surgeon or as an open referral. Only 14% referred directly to a hernia
      specialist and none regularly referred to a laparoscopic surgeon. CONCLUSIONS:
      Referral patterns for inguinal hernia surgery do not reflect services provided in
      secondary care. Further education is required so that a patient's care can be
      optimised.

PMID- 18325216
TI  - Thorascopic sympathectomy performed using laser.
AB  - INTRODUCTION: Thorascopic sympathectomy is accepted as an effective treatment for
      palmar hyperhidrosis, facial blushing and to a lesser extent for digital
      ischaemia and axillary hyperhidrosis. PATIENTS AND METHODS: Data were collected
      retrospectively on patients undergoing thorascopic sympathectomy at St Peter's
      Hospital between 1987 and 2006. Patients were followed up by telephone interview.
      RESULTS: A total of 233 thorascopic sympathectomy procedures were performed by a
      single operator in 123 patients. Ages ranged from 9-71 years and 75 were women.
      In patients, 105 had a bilateral and 13 a unilateral procedure, 5 patients had a
      bilateral procedure performed in two stages. In 6 upper limbs, the procedure
      could not be done. Overall, 110 patients (90%) had the procedure performed for
      palmar hyperhidrosis, 8 (6%) for facial blushing and in 5 (4%) patients the
      operation was performed for digital ischaemia with tissue loss. There were no
      deaths and all patients were discharged on day 1 following the procedure.
      Complications included bleeding (2), pulmonary oedema (1) and failed procedure
      (2); however, no incidences of Horner's syndrome occurred. Only 40 of 123 (32.5%)
      patients gave follow-up information. Of this small group, 33 of 40 (83%) were
      cured, 4 of 40 (10%) were better, 2 of 40 (5%) were unchanged and 1 patient was
      worse. Only 22 out of 40 (55%) of these patients were troubled by compensatory
      sweating, with only 4 of 40 (10%) reporting this as a major problem. CONCLUSIONS:
      Thorascopic sympathectomy is safe and can be carried out as a single bilateral
      procedure in the majority of cases. The laser allows the use of a single port,
      requires less dissection than surgical or clipping techniques, is more precise
      than diathermy and may be less likely to cause a Horner's syndrome.

PMID- 18325217
TI  - Maxillofacial training is no longer than other surgical specialties.
AB  - INTRODUCTION: There is a perception that the training pathway for oral and
      maxillofacial surgery (OMFS) is unduly long and arduous, as consultant oral and
      maxillofacial surgeons must be doubly qualified (that is, hold degrees in
      medicine and dentistry) and be holders of two higher fellowships. MATERIALS AND
      METHODS: We reviewed the data regarding the average age of National Training
      Number (NTN) holders and GMC data on the year of first registration and the year
      of entry onto a specialist surgical list for all 9 surgical specialties. RESULTS:
      The results showed the average age of the surgical SpR populations ranged from
      33.5 to 38.2 years with an average age of 36.14 years. OMFS SpR's average age is
      37.69 years. The GMC data showed the average number of months from full to
      specialist registration ranged from 90.83 months to 135.24 months, with OMFS
      surgeons having the lowest average. CONCLUSIONS: These data suggest that OMFS
      surgeons are of a similar age to other surgeons whilst in training. In addition,
      they have the shortest transit time between full GMC registration and entry onto
      the specialist list. The length of this training even with dual qualification is
      similar to other surgical specialties.

PMID- 18325218
TI  - Written consent - a prospective audit of practices for ENT patients.
AB  - INTRODUCTION: It is very important that patients are given sufficient time to
      consider the implications of surgical treatment. PATIENTS AND METHODS: The
      authors audited the consenting practices for patients undergoing surgery in a
      busy ENT unit. RESULTS: The first cycle demonstrated that 15% of patients were
      providing written consent for surgery on the same day as their operation.
      Subsequent to a simple change in departmental policy, this was reduced to 2%. The
      medicolegal implications of this audit are discussed with reference to current
      recommendations. CONCLUSIONS: This simple policy change not only protects the
      hospital trust from potential litigation but also provides a smooth journey for
      the patients from diagnosis to making the decision to operate and finally to
      undergoing surgery.

PMID- 18325219
TI  - Is routine urine cytology useful in the haematuria clinic?
AB  - INTRODUCTION: The objective of this study was to determine the value of routine
      urine cytology in the initial evaluation of patients presenting to a one-stop
      haematuria clinic. PATIENTS AND METHODS: A total of 1000 consecutive patients who
      attended the haematuria clinic between June 2003 and November 2004 were studied
      prospectively. A standard protocol was used to investigate these patients. This
      included urine cytology, upper tract imaging and flexible cystoscopy. RESULTS:
      Overall, 986 samples of urine were sent for cytology. In 126 patients, the report
      was abnormal; of these, 71 patients were found to have bladder transitional cell
      carcinoma by flexible cystoscopy and a further 3 had upper tract transitional
      cell carcinoma diagnosed radiologically. The remaining 52 patients with abnormal
      cytology were not found to have cancer on further investigations. The total cost
      for urine cytology and additional investigations was pound50,535. CONCLUSIONS: In
      this study of the initial evaluation of patients with haematuria, no case of
      urothelial malignancy was diagnosed on the basis of urine cytology alone.
      Therefore, urine cytology need not be used routinely in the initial diagnostic
      work-up for haematuria.

PMID- 18325220
TI  - Ureteric stent card register - a 5-year retrospective analysis.
AB  - INTRODUCTION: Ureteric stenting is a common urological procedure. Forgotten
      stents have a well-documented morbidity and mortality. Therefore, we asked the
      question, is a stent register an important factor in reducing the number of lost
      or overdue stents? PATIENTS AND METHODS: We conducted a retrospective review of
      203 patients who had ureteric stents inserted in the operating theatre, for the 5
      year period 1 December 1998 to 1 December 2003. We analysed all stent cards,
      patient notes and theatre logs; where no record of stent removal was found, we
      contacted the patient, their GP or their local hospital. RESULTS: A total of 191
      patients were identified from the stent card register. An additional 12 patients
      were found from the theatre logs, but with no record in the stent card register.
      Of the 203 patients, 8 had bilateral stents. The most common indication for
      stenting was stone disease. Of the 203 patients, 11 had overdue stents and 51 had
      no record of the stents ever being removed. The 51 presumed 'forgotten' stents
      were traced, and it was found that 42 patients had had their stents removed by
      other hospitals, and 9 patients died with stents in situ, but before they were
      due for removal. CONCLUSIONS: Our current stent card tracking system is
      ineffective, because it was infrequently reviewed. However, despite overdue and
      'forgotten' stents which were removed by other hospitals, no patients came to any
      real harm and we had no lost stents. Our stent register system did not appear to
      play any role in terms of preventing stent loss, and it seems likely that there
      are other more effective safeguards in place to prevent this from happening.
      However, if a stent register was required at all, a computerised system would be
      preferable. Alternatively, patients could share some of the responsibility of
      stent tracking with their clinicians.

PMID- 18325221
TI  - A role for topical insulin in the management problematic surgical wounds.

PMID- 18325223
TI  - Pre-operative endovascular stenting of the coeliac trunk.

PMID- 18325224
TI  - Use of a styletted spinal needle.

PMID- 18325225
TI  - Capacity and the two-week rule.

PMID- 18325226
TI  - A simpler approach.

PMID- 18325227
TI  - Consideration of mesh-related complications.

PMID- 18325228
TI  - Inferior alveolar nerve block.

PMID- 18325229
TI  - Deja vu.

PMID- 18325230
TI  - Obtaining adequate exposure.

PMID- 18325231
TI  - Biocompatible poly(N-vinyllactam)-based materials with environmentally-responsive
      permeability.
AB  - Biocompatible polymer-based materials whose properties respond to environmental
      stimuli are of great value in biomedical and biotechnological applications (e.g.,
      controlled release of drugs and sensitive reactants, bioseparations, spontaneous
      adjusting of flow of liquids including flow control in microfluidic devices).
      This study describes preparation and properties of biocompatible poly(N
      vinyllactam)-based environment responsive composite membranes. The non-charged
      network N-vinyl lactam polymers form hydrogels that can exhibit swelling and de
      swelling behaviour and, thus, regulate porosity of the membrane. The first part
      of the study has involved investigation of bulk polymerization reactivity of N
      vinylcaprolactam (VCL)-based systems. VCL has been combined with up to 20 mol% of
      N-vinylpyrrolidone (N-vinylbutyrolactam). These synthetic processes have been
      investigated as thermal polymerizations (with and without a free-radical
      initiator) and photopolymerizations. Subsequently, the most reactive systems have
      been used to prepare composite materials by polymerization-modifying borosilicate
      microfibre membranes. The modified membranes have been characterized by the net
      mass gain, infrared spectra, and change in permeability in response to changes in
      ionic strength of the aqueous media. The permeability experiments have been
      carried out at constant fluxes and the resultant changes in trans-membrane
      pressure observed. Those membranes that are ionic-strength responsive could
      potentially be used for bio-separations and other types of biomedical and
      biotechnological applications.

PMID- 18325232
TI  - Surface characterization and in vitro platelet compatibility study of surface
      sulfonated chitosan membrane with amino group protection-deprotection strategy.
AB  - Glycosaminoglycans (GAGs) are the main components of the extracellular matrix
      (ECM). Studies have indicated that scaffolds modified by GAGs could improve cell
      proliferation and differentiation. Chitosan, the second-most abundant nature
      polysaccharide, has a structure similar to that of GAGs. Due to its relatively
      lower cost as compared to GAGs, many researchers have tried to incorporate
      sulfonate or carboxyl groups into the chitosan structure with the aim to form a
      GAG-like structure. However, these modifications were carried out on the reactive
      amino groups that were thought as the major character, resulting in special
      biological properties associated with chitosan. Such a decrease of amino
      functional group density would very likely alter the specific biological
      properties of chitosan. Therefore, an amino group protection-deprotection
      strategy was explored in this study for surface sulfonation of chitosan membrane
      with the aim to imitate GAG structures. Various surface chemical characterization
      results, as well as surface zeta potential measurements have indicated that both
      sulfonate/sulfonic and amino functionalities were coexistent on the deprotected
      sulfonated chitosan specimen. In vitro platelet adhesion testing has shown that
      such a deprotected sulfonated chitosan membrane can increase the amount of
      platelet adhesion while keep those adhered remained unactivated. At the same time
      the presence of deprotected sulfonated chitosan film extended the plasma
      recalcification time value. With this protection-deprotection strategy, a further
      chemical grafting of bioactive molecules, such as RGD peptide, using the
      recovered amino functionalities, can be pursued on these sulfonated chitosan
      specimens.

PMID- 18325233
TI  - Synthesis and anti-cancer efficacy of rapid hydrolysed water-soluble paclitaxel
      pro-drugs.
AB  - A new series of poly(ethylene glycol)(PEG)-paclitaxel conjugates that increases
      water solubility of paclitaxel was synthesized. We developed well-designed self
      immolating linkers between a drug and a water-soluble polymer moiety which gave
      an extremely rapid hydrolysis rate to convert a pro-drug into a parent drug
      without any reduction in drug efficacy. The self-immolating spacer groups were
      introduced between the solubilizing PEG and C7-OH of paclitaxel in order to
      control the rate of enzymatic hydrolysis. All these pro-drugs had a water
      solubility of 400 mg/ml or more compared with a solubility of about 0.01 mg/ml.
      The rate of hydrolysis for the pro-drugs in rat plasma showed considerable
      variation of t((1/2)) ranging from 0.94 min to 42.7 min. To evaluate the anti
      tumor efficacy of the pro-drug which had the fastest enzymatic hydrolysis rate,
      the growth inhibitory effect (IC(50)), the anti-tumor activity and the anti
      metastatic potential of the pro-drug were examined. The pro-drug was potent to
      inhibit the growth of various cancer cell lines, such as human lung, ovarian,
      colon and melanoma cancer cells. On the development of melanoma lung colonies in
      C57B/6 mice following intravenous administration of metastatic murine B16/F10
      melanoma cells, the pro-drug seems to be more efficacious than paclitaxel. The
      reduction of the number of melanoma lung colonies was 46.9% (dose: 5 mg/kg) with
      pure paclitaxel, and 24.5%, and 40.0% with the pro-drug in the dose of 0.71 mg
      paclitaxel equivalent/kg and 1.42 mg paclitaxel equivalent/kg, respectively.

PMID- 18325234
TI  - Preparation and characterization of nano-hydroxyapatite/silk fibroin porous
      scaffolds.
AB  - Novel tissue engineering scaffold materials of nano-hydroxyapatite (nHA)/silk
      fibroin (SF) biocomposite were prepared by freeze-drying. The needle-like nHA
      crystals of about 10 nm in diameter by 50-80 nm in length, which were uniformly
      distributed in the porous nHA/SF scaffolds, were prepared by a co-precipitation
      method with a size. The as-prepared nHA/SF scaffolds showed good homogeneity,
      interconnected pores and high porosity. XRD and FT-IR analysis suggested that the
      silk fibroin was in beta-sheet structure, which usually provides outstanding
      mechanical properties for silk materials. In this work, composite scaffolds
      containing as high as 70% (w/w) nHA were prepared, which had excellent
      compressive modulus and strength, higher than the scaffolds at low nHA content
      level and other porous biodegradable polymeric scaffolds often considered in bone
      related tissue engineering reported previously. The cell compatibility of
      composite scaffolds was evaluated through cell viability by MTT assay. All these
      results indicated that these nHA/SF scaffold materials may be a promising
      biomaterial for bone tissue engineering.

PMID- 18325235
TI  - Electrospun gelatin/poly(L-lactide-co-epsilon-caprolactone) nanofibers for
      mechanically functional tissue-engineering scaffolds.
AB  - Recently, much attention has been given to the fabrication of tissue-engineering
      scaffolds with nano-scaled structure to stimulate cell adhesion and proliferation
      in a microenvironment similar to the natural extracellular matrix milieu. In the
      present study, blends of gelatin and poly(L-lactide-co-epsilon-caprolactone)
      (PLCL) (blending ratio: 0, 30, 70 and 100 wt% gelatin to PLCL) were electrospun
      to prepare nano-structured non-woven fibers for the development of mechanically
      functional engineered skin grafts. The resulting nanofibers demonstrated the
      uniform and smooth fibers with mean diameters ranging from approx. 50 to 500 nm
      with interconnected pores, regardless of the composition. The contact angle
      decreased with increasing amount of gelatin in the blend and the water content of
      the nanofibers increased concurrently. PLCL nanofibers retained significant
      levels of recovery following application of uniaxial stress; GP-3 with 70% PLCL
      blend returned to the original length within less than 10% of deformation
      following 200% of uniaxial elongation. The overall tensile strength was inversely
      affected by increase in the gelatin content and degradation rates of the
      nanofibers were accelerated as the gelatin concentration increased. When seeded
      with human primary dermal fibroblasts and keratinocytes on the nanofibers, both
      initial cell adhesion and proliferation rate increased as a function of the
      gelatin content in the blend. Additionally, the total cell number was
      significantly greater on the nanofiber scaffolds than on polymer-coated glasses,
      indicating that nanofibrous structure facilitates cell proliferation. Taken
      together, gelatin/PLCL blend nanofiber scaffolds may serve as a promising
      artificial extracellular matrix for regeneration of mechanically functional skin
      tissue.

PMID- 18325236
TI  - Eluting characteristics of a platelet glycoprotein receptor antibody using a PLLA
      coated stent.
AB  - Drug-eluting stents (DES) have emerged as a recognized alternative to treat stent
      restenosis but many questions remain regarding the optimal type and eluting
      characteristics of both drug and stent. The first component of the study examines
      the extent of surface coating of PLLA (poly(L-lactic acid)) on a Nitinol stent.
      The second characterizes the adsorption and elution rates of monoclonal mouse
      anti-human platelet glycoprotein (GP) IIIa antibody SZ-21 from a PLLA-coated
      surface. The PLLA coating was examined by fluorescence staining and image
      analysis using the Image Processing Box of MATLAB. Stents exposed to the
      monoclonal mouse anti-human platelet GP IIIa antibody were tested for their
      adsorption characteristics by radioisotope technique with (125)I-labelled SZ-21.
      The elution rates were then measured in looped circuits at different velocities
      (10 or 20 ml/min) and durations (30 min up to 312 h). Results showed that the
      fluorescence staining and image analysis showed a striking difference in the
      extent of coating between PLLA-coated stents and SZ-21 eluting stents on the gray
      scale distribution of Nitinol surfaces. The amount of SZ-21 adsorbed onto the
      PLLA-coated stents was dependent on the concentration and duration of immersion
      in the solution. The method of preparation the mAb eluting stent significantly
      influenced the elution characteristics for a continuous perfusion of more than
      300 h. The eluting curve was biphasic with initial rapid elution for the first 24
      h followed by a gradual slow elution. These results indicate that the Image
      Processing Box of MATLAB appears to be a useful method for semi-quantitative
      analysis of fluorescence images. Furthermore, SZ-21 can be passively adsorbed
      onto PLLA-coated stents and predictably influenced by the concentration and
      duration of immersion. These studies may pave the way to developing stent-based
      delivery of a potent anti-platelet agent.

PMID- 18325237
TI  - Antibacterial and antimycotic activity of a cross-linked electrospun poly(vinyl
      pyrrolidone)-iodine complex and a poly(ethylene oxide)/poly(vinyl pyrrolidone)
      iodine complex.
AB  - Photo-cross-linked poly(vinyl pyrrolidone) (PVP) and poly(ethylene
      oxide)(PEO)/PVP electrospun nanofibrous mats containing complex-bound iodine have
      been studied. FT-IR spectroscopy analyses have proved that coordination of
      molecular iodine with carbonyl group and nitrogen atom of pyrrolidone rings of
      the PVP chains has taken place. The distribution of iodine along the fibers is
      uniform as revealed by X-ray mapping. The microbiological tests have demonstrated
      that the iodine complex-containing electrospun mats are highly effective against
      the Gram-positive bacterium Staphylococcus aureus, the Gram-negative bacterium
      Escherichia coli and the fungus Candida albicans. Comparison with iodine complex
      containing films has shown that the iodine complex-containing nanofibers exhibit
      a higher killing rate than the films against bacteria E. coli. SEM observations
      showed that PVP-iodine nanofibrous mats inhibit the adhesion of bacteria S.
      aureus. These characteristic features make the electrospun iodine-containing
      nanofibers good candidates for wound-dressing materials.

PMID- 18325238
TI  - Toxicological evaluation of lactose and chitosan delivered by inhalation.
AB  - These days, inhalation constitutes a promising administration route for many
      drugs. However, this route exhibits unique limitations, and formulations aimed at
      pulmonary delivery should include as few as possible additives in order to
      maintain lung functionality. The purpose of this work was to investigate the
      safety of lactose and chitosan to the pulmonary tissue when delivered by
      inhalation. The study was carried out with 18 Wistar rats divided in three groups
      receiving distilled water, lactose or chitosan. A solution of each excipient was
      administered by inhalation at a dose of 20 mg. The lungs were excised and
      processed to determine several biochemical parameters used as toxicity
      biomarkers. Protein and carbonyl group content, lipid peroxidation, reduced and
      oxidized glutathione (GSSG), myeloperoxidase (MPO), cooper/zinc and manganese
      superoxide dismutase, catalase, glutathione S-transferase and glutathione
      peroxidase were determined. Results of myeloperoxidase activity and glutathione
      disulfide lung concentrations showed a relevant decrease for chitosan group
      compared to control: 4.67 +/- 2.27 versus 15.10 +/- 7.27 (P = 0.011) for MPO and
      0.89 +/- 0.68 versus 2.02 +/- 0.22 (P = 0.014) for GSSG. The other parameters did
      not vary significantly among groups. Lactose and chitosan administered by
      inhalation failed to show toxic effects to the pulmonary tissue. A protective
      effect against oxidative stress might even be attributed to chitosan, since some
      biomarkers had values significantly lower than those observed in the control
      group when this product was inhaled. Nevertheless, caution must be taken
      regarding chemical composition and technological processes applied to incorporate
      these products during drug formulation, in particular for dry powder inhalators.

PMID- 18325239
TI  - A novel construct as a cell carrier for tissue engineering.
AB  - A 3D scaffold, in the form of a foam, with the top surface carrying a
      micropattern, was constructed from biodegradable polyesters poly(3-hydroxybutyric
      acid-co-3-hydroxyvaleric acid) (PHBV) and poly(L-lactide-co-D,L-lactide)
      (P(L/DL)LA) to serve as a substitute for the extracellular matrix (ECM) of
      tissues with more than one cell type. The construct was tested in vitro for
      engineering of such tissues using fibroblasts (3T3) and epithelial cells (retinal
      pigment epithelial cells, D407). The patterned surface was seeded with D407 cells
      and the foam was seeded with 3T3 cells to represent a tissue with two different
      cell types. To improve cell adhesion, the construct was treated with fibronectin.
      The cells were seeded on the construct in a sequence allowing each type time for
      adhesion. Cell proliferation, studied by MTS assay, was significantly higher than
      that of tissue culture polystyrene control by day 14. Scanning electron and
      fluorescence microscopy showed that the foam side of the construct was highly
      porous and the pores were interconnected and this allowed cell mobility and
      proliferation. Immunostaining showed collagen deposition, indicating the
      secretion of the new ECM by the cells. On the film side of the construct D407
      cells formed piles in the grooves and covered the surface completely. It was
      concluded that the 3D P(L/DL)LA-PHBV construct with one micropatterned surface
      has a serious potential for use as a tissue engineering carrier in the
      reconstruction of complex tissues with layered organization and different types
      of cells in each region.

PMID- 18325241
TI  - [Obesity is more than an eating disorder--the multidimensional perspective of a
      pandemia].
AB  - A summary of the epidemiology, etiology and therapy of obesity is given with
      special emphasis on psychosomatic aspects. Overweight and obesity are widespread
      and go hand in hand with an increased health risk. The etiology of obesity is
      multifactorial based on gene/environment interactions; hyperalimentation and
      physical inactivity, as an expression of the rapid technical advancements within
      the past decades, have, however, had a decisive influence on the pandemic
      spreading of obesity. The prevalence of mental disorders is increased
      particularly in obese women. Although phylogenetically of relevance, an
      environment that associates slimness with beauty, health, physical and mental
      proficiency leads to a stigmatization of the obese. The results are mental
      symptoms and disorders. On the contrary, mental problems up to and including the
      full clinical picture of mental disorders may lead to changes in eating and
      exercise behaviour, the result of which may be a sustained positive energy
      balance with overweight and obesity. The success of conservative weight reduction
      measures in obesity is inadequate. Surgical measures are more successful, but
      they are only indicated for severe obesity. The psychosomatic and
      psychotherapeutic approach to overweight and obesity is multifactorial and
      indispensable. Obesity is not an eating disorder; it may, however, be the result
      of hyperalimentation into which pathogenetic and mental factors have been
      incorporated.

PMID- 18325242
TI  - [Barbie goes PriMa: formative evaluation of a school-based program for the
      primary prevention of anorexia nervosa developed for girls up to the age of 12].
AB  - OBJECTIVES: Recently, a newly developed German program for the prevention of
      anorexia nervosa in girls ("PriMa") was successfully tested for effectiveness in
      a controlled study with prepost-design in 1,006 girls from 42 Thuringian schools
      (Berger et al. 2007). In the present article the test of the program's
      effectiveness was completed by an evaluation of the program's conception and its
      process. METHOD: Using questionnaires, protocols and phone interviews, single
      parts of the program (kick-off presentation, n = 400; teachers training, n = 34;
      lessons, n = 392) as well as single lessons (n = 87 girls and n = 14 teachers)
      were evaluated. RESULTS: All parts of the program were evaluated as being
      significantly positive (better than 2.5 on a six-point scale). The questionnaires
      used were reliable (Cronbach's alpha between .74 and .84). The survey of program
      users resulted in shorter research questionnaires, a more detailed teaching
      manual with more interactive exercises and smaller training groups (14 instead of
      20 participants). DISCUSSION: The introduced work points out the need to complete
      the evaluation of program impact with verbal and written evaluations of direct
      and indirect program users. This is the only way to reveal information about the
      program's strengths and weaknesses to continuously adjust and improve single
      program parts.

PMID- 18325243
TI  - [Validity of axis III "Conflicts" of Operationalized Psychodynamic Diagnostics
      (OPD-1)--empirical results and conclusions for OPD-2].
AB  - OBJECTIVE: Using specific psychometric instruments, we investigate criteria
      related validity of axis III ("conflicts") of OPD-1 by a priori formulated
      hypotheses concerning the relations to the main conflict/mode. METHODS/SAMPLE: A
      consecutive sample of 105 psychotherapy inpatients was examined using self
      assessment scales (Inventory of Interpersonal Problems; Rosenberg Self-Esteem
      Scale, Test of Self-Conscious Affect; Toronto Alexithymia-Scale; Frankfurt Self
      Concept Scales) and videotaped OPD research interviews in the first week after
      admission to the hospital. Two OPD-certified raters first rated the interviews
      independently, then in a consensus rating. RESULTS: Due to the different
      frequency of the main conflict and mode, evaluation of 4 of 7 conflicts was
      possible. The a priori hypotheses could be confirmed for the conflicts Dependence
      versus Autonomy (both modes), Submission versus Control (active mode), Desire for
      Care versus Autarchy (active mode), and Self-Value (passive mode). DISCUSSION:
      Confirmation of the a priori hypotheses indicates validity of axis III
      (Conflicts) of OPD. We discuss the small numbers of some conflicts, the
      comparison of expert rating OPD with self-assessment and the meaning of the
      results for OPD-2.

PMID- 18325244
TI  - [Predictors of dropout during psychoanalytic treatments of patients with
      personality disorders].
AB  - OBJECTIVES: Are there predictive factors which impair the progress in
      psychoanalytic treatments of patients with severe personality disorders? METHODS:
      In 38 psychoanalytic treatments, severity of symptoms (SCL-90-R), interpersonal
      problems (IIP), character traits and psychostructural functioning (SWAP-200) were
      investigated half-yearly. Predictors for drop-out were identified using stepwise
      binary logistic regression models and repeated ANOVA models. The statistical
      stability was controlled using a jackknife algorithm. RESULTS: For the first year
      denial of needs for closeness, conflicts around engagement and abandonment, as
      well as fears of an impulsive breakthrough of negative affects predicted dropout
      of therapy. During the second year externalizing defence, projection/projective
      identification, somatisation, hypochondria and dismissive interpersonal behaviour
      predicted break-ups. CONCLUSIONS: For psychoanalytic technique, it is necessary
      to perceive and catch paranoid anxieties, negative affects, externalizing
      mechanisms and projective identification from the very beginning as well as to
      interpret and work through these elements in transference thoroughly in order to
      prevent treatment dropout.

PMID- 18325245
TI  - [Metaphors and affect: their interrelation in the therapeutic process].
AB  - OBJECTIVES: In accordance with Freud's hypothesis about the nature of primary
      process thinking we analysed metaphors as possible tools for the integration of
      unconscious affective und cognitive representational processes which, besides
      being complementary to affective interactive dyadic behaviour, may be of curative
      value. METHODS: Using videotapes of 10 fifteen-hour short-term therapies by very
      experienced therapists treating an unselected group of patients, facial affect
      and metaphoric language of the therapist and the patient as well as the temporal
      distance between the two was recorded. RESULTS: The density of metaphors was not
      significantly correlated with symptom reduction but with treatment satisfaction.
      However, symptom reduction correlated significantly with the frequency of
      interactive metaphors used by both the therapist and the patient. CONCLUSIONS: It
      could be shown that there is an optimal time window between facial affect and
      metaphor production beyond the here and now, but not as a long term memory.

PMID- 18325247
TI  - Rescinding community mitigation strategies in an influenza pandemic.
AB  - Using a networked, agent-based computational model of a stylized community, we
      evaluated thresholds for rescinding 2 community mitigation strategies after an
      influenza pandemic. We ended child sequestering or all-community sequestering
      when illness incidence waned to thresholds of 0, 1, 2, or 3 cases in 7 days in 2
      levels of pandemic severity. An unmitigated epidemic or strategy continuation for
      the epidemic duration served as control scenarios. The 0-case per 7-day
      rescinding threshold was comparable to the continuation strategy on infection and
      illness rates but reduced the number of days strategies would be needed by 6% to
      32% in mild or severe pandemics. If cases recurred, strategies were resumed at a
      predefined 10-case trigger, and epidemic recurrence was thwarted. Strategies were
      most effective when used with high compliance and when combined with stringent
      rescinding thresholds. The need for strategies implemented for control of an
      influenza pandemic was reduced, without increasing illness rates.

PMID- 18325248
TI  - Mycobacterium ulcerans disease, Peru.
AB  - Eight adult patients (ages 18-58, 5 women) with Buruli ulcer (BU) confirmed by at
      least 2 diagnostic methods were seen in a 10-year period. Attempts to culture
      Mycobacterium ulcerans failed. Five patients came from jungle areas, and 3 from
      the swampy northern coast of Peru. The patients had 1-5 lesions, most of which
      were on the lower extremities. One patient had 5 clustered gluteal lesions;
      another patient had 2 lesions on a finger. Three patients were lost to follow-up.
      All 5 remaining patients had moderate disease. Diverse treatments
      (antituberculous drugs, World Health Organization [WHO] recommended antimicrobial
      drug treatment for BU, and for 3 patients, excision surgery) were successful.
      Only 1 patient (patient 7) received the specific drug treatment recommended by
      WHO. BU is endemic in Peru, although apparently infrequent. Education of
      populations and training of health workers are first needed to evaluate and
      understand the full extent of BU in Peru.

PMID- 18325250
TI  - Multicenter cross-sectional study of nontuberculous mycobacterial infections
      among cystic fibrosis patients, Israel.
AB  - This 2-year cross-sectional evaluation of nontuberculous mycobacterial (NTM)
      infections involved all Israeli medical centers that treat cystic fibrosis
      patients. The study comprised 186 patients whose sputum was analyzed for NTM. The
      prevalence of NTM isolates was 22.6%, and 6.5% and 10.8% of the patients
      fulfilled the 1997 and 2007 American Thoracic Society criteria for NTM lung
      disease, respectively. Mycobacterium simiae (40.5%), M. abscessus (31.0%), and M.
      avium complex (14.3%) were the most prevalent. Presence of Aspergillus spp. in
      sputum and the number of sputum specimens processed for mycobacteria were the
      most significant predictors for isolation of NTM (odds ratio [OR] = 5.14, 95%
      confidence interval [CI] 1.87-14.11 and OR = 1.47, 95% CI 1.17-1.85,
      respectively). The incidence of NTM pulmonary infections is increasing among
      cystic fibrosis patients, reflecting the increase in longevity of such patients
      as well as environmental exposure to various species of mycobacteria.

PMID- 18325251
TI  - Mycobacterium xenopi clinical relevance and determinants, the Netherlands.
AB  - In the Netherlands, isolation of Mycobacterium xenopi is infrequent, and its
      clinical relevance is often uncertain. To determine clinical relevance and
      determinants, we retrospectively reviewed medical files of all patients in the
      Netherlands in whom M. xenopi was isolated from January 1999 through March 2005
      by using diagnostic criteria for nontuberculous mycobacterial infection published
      by the American Thoracic Society. We found 49 patients, mostly white men, with an
      average age of 60 years and pre-existing pulmonary disease; of these patients, 25
      (51%) met the diagnostic criteria. Mycobacterial genotype, based on 16S rRNA gene
      sequencing, was associated with true infection. Most infections were pulmonary,
      but pleural and spinal infections (spinal in HIV-infected patients) were also
      noted. Treatment regimens varied in content and duration; some patients were over
      treated and some were undertreated.

PMID- 18325252
TI  - Epidemiology of nontuberculous mycobacteria in patients without HIV infection,
      New York City.
AB  - We reviewed medical records of patients without known HIV and with positive
      cultures for nontuberculous mycobacteria (NTM) isolated during 2000-2003 from 1
      large hospital in New York, New York. Overall, 505 patients had positive NTM
      cultures; 119 (24%) met the criteria for NTM disease. The difference between
      demographic characteristics of case-patients in our study (66% female, 61% white,
      and 59% > 60 years of age) and those of the base population as determined by
      regional census data was statistically significant. Estimated incidences for
      positive cultures, all disease, and respiratory tract disease were 17.7, 2.7, and
      2.0 per 100,000 persons, respectively. More patients with rapidly growing
      mycobacteria (61%), Mycobacterium kansasii (70%), or M. marinum (100%) met
      criteria for disease than did patients with M. avium complex (MAC) (27%, (p <
      0.01). NTM disease in patients without HIV is increasing. Laboratory-based
      surveillance may be useful for detecting non-MAC and non-respiratory tract
      disease.

PMID- 18325253
TI  - Exposure to novel parainfluenza virus and clinical relevance in 2 bottlenose
      dolphin (Tursiops truncatus) populations.
AB  - Parainfluenza virus (PIV) is a leading cause of respiratory infections in humans.
      A novel virus closely related to human and bovine parainfluenza viruses types 3
      (HPIV-3 and BPIV-3), named Tursiops truncatus parainfluenza virus type 1 (TtPIV
      1), was isolated from a dolphin with respiratory disease. We developed a dolphin
      specific ELISA to measure acute- and convalescent-phase PIV antibodies in
      dolphins during 1999-2006 with hemograms similar to that of the positive control.
      PIV seroconversion occurred concurrently with an abnormal hemogram in 22 animals,
      of which 7 (31.8%) had respiratory signs. Seroprevalence surveys were conducted
      on 114 healthy bottlenose dolphins in Florida and California. When the most
      conservative interpretation of positive was used, 11.4% of healthy dolphins were
      antibody positive, 29.8% were negative, and 58.8% were inconclusive. PIV appears
      to be a common marine mammal virus that may be of human health interest because
      of the similarity of TtPIV-1 to BPIV-3 and HPIV-3.

PMID- 18325254
TI  - Hantavirus RNA in saliva from patients with hemorrhagic fever with renal
      syndrome.
AB  - Hantaviruses cause 2 zoonotic diseases, hemorrhagic fever with renal syndrome
      (HFRS) and hantavirus cardiopulmonary syndrome. Infection is usually initiated
      after inhalation of virus-contaminated rodent excreta. In addition to the
      zoonotic infection route, growing evidence suggests person-to-person transmission
      of Andes virus. For this reason, we studied whether saliva from HFRS patients
      contained hantavirus. During an outbreak in northern Sweden of nephropathia
      epidemica (NE), a milder form of hemorrhagic fever with renal syndrome, we
      collected saliva and plasma from 14 hospitalized NE patients with verified
      Puumala virus (PUUV) infection. PUUV RNA was detected in saliva from 10 patients
      (range 1,530-121,323 PUUV RNA copies/mL) by quantitative reverse transcription
      PCR. The PUUV S-segment sequences from saliva and plasma of the same patients
      were identical. Our data show that hantavirus RNA could be detected in human
      saliva several days after onset of disease symptoms and raise the question
      whether interhuman transmission of hantavirus may occur through saliva.

PMID- 18325255
TI  - Increased mortality rate associated with chikungunya epidemic, Ahmedabad, India.
AB  - In 2005-2006, Reunion Island in the Indian Ocean reported approximately 266,000
      cases of chikungunya; 254 were fatal (case-fatality rate 1/1,000). India reported
      1.39 million cases of chikungunya fever in 2006 with no attributable deaths;
      Ahmedabad, India, reported 60,777 suspected chikungunya cases. To assess the
      effect of this epidemic, mortality rates in 2006 were compared with those in 2002
      2005 for Ahmedabad (population 3.8 million). A total of 2,944 excess deaths
      occurred during the chikungunya epidemic (August-November 2006) when compared
      with the average number of deaths in the same months during the previous 4 years.
      These excess deaths may be attributable to this epidemic. However, a hidden or
      unexplained cause of death is also possible. Public health authorities should
      thoroughly investigate this increase in deaths associated with this epidemic and
      implement measures to prevent further epidemics of chikungunya.

PMID- 18325256
TI  - Chikungunya fever in travelers returning to Europe from the Indian Ocean region,
      2006.
AB  - Chikungunya fever has spread through several Indian Ocean islands and India,
      including popular travel destinations. To compare usefulness of diagnostic tests
      and to understand reasons for the magnitude and severity of an outbreak, we used
      3 diagnostic methods to test 720 samples from 680 patients returning to Europe
      from the Indian Ocean region in 2006. Chikungunya infection was confirmed for
      24.4% patients in the first half of the year and for 9.9% in the second half.
      Reverse transcription-PCR was positive for all samples taken up to day 4 after
      symptom onset. Immunofluorescence detected immunoglobulin (Ig) M on day 1 and IgG
      on day 2 for some patients, and in all patients from day 5 onward. Soon after
      onset of symptoms, patients had IgG and IgM and high viral loads (some >10(9)
      copies/mL plasma). These data will help healthcare providers select diagnostic
      tests for returning travelers.

PMID- 18325257
TI  - High rate of mobilization for blaCTX-Ms.
AB  - We constructed a phylogenetic analysis of class A beta-lactamases and found that
      the blaCTX-Ms have been mobilized to plasmids approximately 10 times more
      frequently than other class A beta-lactamases. We also found that the blaCTX-Ms
      are descended from a common ancestor that was incorporated in ancient times into
      the chromosome of the ancestor of Kluyvera species through horizontal transfer.
      Considerable sequence divergence has occurred among the descendents of that
      ancestral gene sequence since that gene was inserted. That divergence has mainly
      occurred in the presence of purifying selection, which indicates a slow rate of
      evolution for blaCTX-Ms in the pre-antimicrobial drug era.

PMID- 18325258
TI  - Integrated food chain surveillance system for Salmonella spp. in Mexico.
AB  - Few developing countries have foodborne pathogen surveillance systems, and none
      of these integrates data from humans, food, and animals. We describe the
      implementation of a 4-state, integrated food chain surveillance system (IFCS) for
      Salmonella spp. in Mexico. Significant findings were 1) high rates of meat
      contamination (21.3%-36.4%), 2) high rates of ceftriaxone-resistant S.
      Typhimurium in chicken, ill humans, and swine (77.3%, 66.3%, and 40.4% of S.
      Typhimurium T isolates, respectively), and 3) the emergence of ciprofloxacin
      resistance in S. Heidelberg (10.4%) and S. Typhimurium (1.7%) from swine. A
      strong association between Salmonella spp. contamination in beef and asymptomatic
      Salmonella spp. infection was only observed in the state with the lowest poverty
      level (Pearson r = 0.91, p<0.001). Pulsed-field gel electrophoresis analysis of
      311 S. Typhimurium isolates showed 14 clusters with 102 human, retail meat, and
      food-animal isolates with indistinguishable patterns. An IFCS is technically and
      economically feasible in developing countries and can effectively identify major
      public health priorities.

PMID- 18325259
TI  - Genetic variability of West Nile virus in US blood donors, 2002-2005.
AB  - West Nile virus (WNV) was detected in the United States in 1999, has reoccurred
      every summer since, and has become endemic. Transfusion transmission was
      documented in 2002, and screening of blood donations for WNV began in 2003. We
      investigated genetic variation of WNV in human isolates obtained from specimens
      collected from 30 infected blood donors who tested positive for WNV RNA during
      2002-2005. Complete genomic sequences of 8 isolates and structural gene sequences
      from 22 additional isolates were analyzed. We found some genetic diversity in
      isolates from different geographic regions and genetic divergence from reported
      sequences from epidemics in 1999-2001. Nucleotide divergence of structural genes
      showed a small increase from 2002 (0.18%) to 2005 (0.37%), suggesting absence of
      strong selective pressure and limited genetic evolution of WNV during that
      period. Nevertheless, WNV has continued to diverge from precursor isolates as
      geographic distribution of the virus has expanded.

PMID- 18325260
TI  - Discovering and differentiating new and emerging clonal populations of Chlamydia
      trachomatis with a novel shotgun cell culture harvest assay.
AB  - Chlamydia trachomatis is the leading cause of preventable blindness and bacterial
      sexually transmitted diseases worldwide. Plaque assays have been used to clonally
      segregate laboratory-adapted C. trachomatis strains from mixed infections, but no
      assays have been reported to segregate clones from recent clinical samples. We
      developed a novel shotgun cell culture harvest assay for this purpose because we
      found that recent clinical samples do not form plaques. Clones were strain-typed
      by using outer membrane protein A and 16S rRNA sequences. Surprisingly, ocular
      trachoma reference strain A/SA-1 contained clones of Chlamydophila abortus. C.
      abortus primarily infects ruminants and pigs and has never been identified in
      populations where trachoma is endemic. Three clonal variants of reference strain
      Ba/Apache-2 were also identified. Our findings reflect the importance of clonal
      isolation in identifying constituents of mixed infections containing new or
      emerging strains and of viable clones for research to more fully understand the
      dynamics of in vivo strain-mixing, evolution, and disease pathogenesis.

PMID- 18325261
TI  - Molecular epidemiology of eastern equine encephalitis virus, New York.
AB  - Perpetuation, overwintering, and extinction of eastern equine encephalitis virus
      (EEEV) in northern foci are poorly understood. We therefore sought to describe
      the molecular epidemiology of EEEV in New York State during current and past
      epizootics. To determine whether EEEV overwinters, is periodically reintroduced,
      or both, we sequenced the E2 and partial NSP3 coding regions of 42 EEEV isolates
      from New York State and the Eastern Seaboard of the United States. Our
      phylogenetic analyses indicated that derived subclades tended to contain southern
      strains that had been isolated before genetically similar northern strains,
      suggesting southern to northern migration of EEEV along the Eastern Seaboard.
      Strong clustering among strains isolated during epizootics in New York from 2003
      2005, as well as from 1974-1975, demonstrates that EEEV has overwintered in this
      focus. This study provides molecular evidence for the introduction of southern
      EEEV strains to New York, followed by local amplification, perpetuation, and
      overwintering.

PMID- 18325262
TI  - Transmission of equine influenza virus to English foxhounds.
AB  - We retrospectively demonstrated that an outbreak of severe respiratory disease in
      a pack of English foxhounds in the United Kingdom in September 2002 was caused by
      an equine influenza A virus (H3N8). We also demonstrated that canine respiratory
      tissue possesses the relevant receptors for infection with equine influenza
      virus.

PMID- 18325263
TI  - Screening pneumonia patients for mimivirus.
AB  - Acanthamoeba polyphaga mimivirus (APM), a virus of free-living amebae, has
      reportedly caused human respiratory disease. Using 2 newly developed real-time
      PCR assays, we screened 496 respiratory specimens from 9 pneumonia-patient
      populations for APM. This virus was not detected in any specimen, which suggests
      it is not a common respiratory pathogen.

PMID- 18325264
TI  - Protective effect of maritime quarantine in South Pacific jurisdictions, 1918-19
      influenza pandemic.
AB  - We reviewed mortality data of the 1918-19 influenza pandemic for 11 South Pacific
      Island jurisdictions. Four of these appear to have successfully delayed or
      excluded the arrival of pandemic influenza by imposing strict maritime
      quarantine. They also experienced lower excess death rates than the other
      jurisdictions that did not apply quarantine measures.

PMID- 18325265
TI  - Dolphin morbillivirus epizootic resurgence, Mediterranean Sea.
AB  - In July 2007, > 100 striped dolphins, Stenella coeruleoalba, were found dead
      along the coast of the Spanish Mediterranean. Of 10 dolphins tested, 7 were
      positive for a virus strain closely related to the dolphin morbillivirus that was
      isolated during a previous epizootic in 1990.

PMID- 18325266
TI  - Gastroenteritis outbreak at holiday resort, central Italy.
AB  - During the summer of 2003, a gastroenteritis outbreak spread throughout a holiday
      resort in central Italy. Fecally contaminated groundwater and seawater were
      leaking into the non-drinking-water system, which was found to be connected to
      the drinking-water system of a large resort. This contamination had a primary
      role in the onset of the outbreak and spread of the infection.

PMID- 18325267
TI  - Methicillin-resistant and -susceptible Staphylococcus aureus sequence type 398 in
      pigs and humans.
AB  - Methicillin-resistant Staphylococcus aureus sequence type 398 (ST398 MRSA) was
      identified in Dutch pigs and pig farmers. ST398 methicillin-susceptible S. aureus
      circulates among humans at low frequency (0.2%) but was isolated in 3 human cases
      of bacteremia (2.1%; p = 0.026). Although its natural host is probably porcine,
      ST398 MRSA likely causes infections in humans.

PMID- 18325268
TI  - Hemagglutinating encephalomyelitis coronavirus infection in pigs, Argentina.
AB  - We describe an outbreak of vomiting, wasting, and encephalomyelitis syndrome in
      piglets in Argentina, caused by porcine hemagglutinating encephalomyelitis
      coronavirus (PHE-CoV) infection. Diagnosis was made by epidemiologic factors,
      pathologic features, immunohistochemistry, reverse transcription-PCR, and genomic
      sequencing. This study documents PHE-CoV infection in South America.

PMID- 18325269
TI  - Highly pathogenic avian influenza virus (H5N1) in domestic poultry and
      relationship with migratory birds, South Korea.
AB  - During the 2006-2007 winter season in South Korea, several outbreaks of highly
      pathogenic avian influenza virus (H5N1) were confirmed among domestic poultry and
      in migratory bird habitats. Phylogenetic analysis showed that all isolates were
      closely related and that all belong to the A/bar-headed goose/Qinghai/5/2005-like
      lineage rather than the A/chicken/Korea/ES/2003-like lineage.

PMID- 18325270
TI  - Mutations in influenza A virus (H5N1) and possible limited spread, Turkey, 2006.
AB  - We report mutations in influenza A virus (H5N1) strains associated with 2
      outbreaks in Turkey. Four novel amino acid changes (Q447L, N556K, and R46K in RNA
      polymerase and S133A in hemagglutinin) were detected in virus isolates from 2
      siblings who died.

PMID- 18325271
TI  - Ciprofloxacin-resistant Salmonella enterica serotype Typhimurium, China.
AB  - We characterized 44 Salmonella enterica serotype Typhimurium isolates from Tongji
      Hospital outpatients in Wuhan, China, May 2002-October 2005. All 31 ciprofloxacin
      resistant isolates were also resistant to > or = 8 other antimicrobial drugs and
      carried > or = 2 mutations in GyrA and 1 mutation in ParC. Class 1 integrons were
      identified in 37 isolates.

PMID- 18325272
TI  - Geographic linkage and variation in Cryptosporidium hominis.
AB  - UK Cryptosporidium hominis isolates have previously shown slight PCR fragment
      length polymorphism at multiple loci. To further investigate transmission, we
      conducted a case-control study and sequenced the GP60 locus from 115 isolates.
      Nine subtypes were identified; IbA10G2 predominated. Having a non-IbA10G2 subtype
      was significantly linked to recent travel outside Europe.

PMID- 18325273
TI  - Low frequency of infection with avian influenza virus (H5N1) among poultry
      farmers, Thailand, 2004.
AB  - In Thai provinces where avian influenza outbreaks in poultry had been confirmed
      in the preceding 6 months, serum from 322 poultry farmers was tested for
      antibodies to avian influenza virus subtype H5N1 by microneutralization assay. No
      study participant met the World Health Organization serologic criteria for
      confirmed infection.

PMID- 18325274
TI  - Sylvatic dengue virus type 2 activity in humans, Nigeria, 1966.
AB  - Using phylogenetic analysis of complete virus genomes from human isolates
      obtained in Nigeria in 1966, we identified sylvatic dengue virus (DENV) strains
      from 3 febrile patients. This finding extends current understanding of the role
      of sylvatic DENV in febrile disease and documents another focus of sylvatic DENV
      transmission in West Africa.

PMID- 18325275
TI  - Leptospirosis-associated severe pulmonary hemorrhagic syndrome, Salvador, Brazil.
AB  - We report the emergence of leptospirosis-associated severe pulmonary hemorrhagic
      syndrome (SPHS) in slum communities in Salvador, Brazil. Although active
      surveillance did not identify SPHS before 2003, 47 cases were identified from
      2003 through 2005; the case-fatality rate was 74%. By 2005, SPHS caused 55% of
      the deaths due to leptospirosis.

PMID- 18325276
TI  - Pandemic influenza, reopening schools, and returning to work.

PMID- 18325277
TI  - On Rickettsia nomenclature.

PMID- 18325278
TI  - Multidrug-resistant Acinetobacter baumannii osteomyelitis from Iraq.

PMID- 18325279
TI  - Hospital resources for pandemic influenza.

PMID- 18325280
TI  - Dengue virus, Nepal.

PMID- 18325281
TI  - Human tuberculosis caused by Mycobacterium bovis, Taiwan.

PMID- 18325282
TI  - Marine mammal Brucella genotype associated with zoonotic infection.

PMID- 18325283
TI  - Ehrlichia chaffeensis in child, Venezuela.

PMID- 18325284
TI  - Resource allocation during an influenza pandemic.

PMID- 18325285
TI  - Novel relapsing fever spirochete in bat tick.

PMID- 18325286
TI  - KI and WU polyomaviruses in children, France.

PMID- 18325287
TI  - Milk replacers and bovine spongiform encephalopathy in calves, Japan.

PMID- 18325288
TI  - Control of hepatitis A by universal vaccination of adolescents, Puglia, Italy.

PMID- 18325289
TI  - Lymphangitis in a Portuguese patient infected with Rickettsia sibirica.

PMID- 18325294
TI  - Spontaneous intracranial hypotension: the syndrome and its complications.
AB  - Spontaneous intracranial hypotension (SIH) is a syndrome that was largely unknown
      until the advent of MRI. The incidence of SIH is estimated at 5 per 100,000,
      which is half the incidence of subarachnoid hemorrhage. The major feature is a
      postural headache of acute or subacute onset. This headache is absent or minimal
      when the patient is lying down and rapidly worsens to great intensity when the
      patient sits or stands. Other features may include nausea, vomiting, vertigo,
      tinnitus, and marked exacerbation by Valsalva maneuver. SIH is due to a leak of
      cerebrospinal fluid from a tear in the dural membrane, which occurs most often at
      the exit zones where the cervical spinal roots leave the subarachnoid space.
      Other leak sites may be the vestibular system, the cribriform plate, or the
      pituitary fossa. If the leak continues, the brain loses buoyancy within the
      cranial space and sags toward the foramen magnum. This, in turn, may produce
      subdural hygroma or hematoma, brainstem compression, focal cranial nerve palsies,
      or cerebellar tonsillar herniation. The initial therapy is generally strict bed
      rest. If this fails, an epidural blood patch is usually successful in sealing the
      leak and restoring brain buoyancy. A significant minority of patients require a
      repeat epidural blood patch. If the blood patch fails, a surgical approach may be
      needed. Repair of the leak and restoration of brain buoyancy will stop the
      postural headache and, in most cases, will reverse the complications.

PMID- 18325295
TI  - Headache related to pregnancy: management of migraine and migraine headache in
      pregnancy.
AB  - Evidence-based treatment algorithms are needed for managing headache during
      conception, pregnancy, and the postpartum period. Whereas most studies seem to
      indicate that headaches improve for most women during pregnancy (as estrogen
      levels increase), this often is not the case in women with more severe, frequent
      migraine. Few pharmacologic studies include pregnant women, so evidence-based
      treatments are lacking. Pregnancy registries to record adverse outcomes for
      various medications and large, population-based studies are needed to analyze the
      behavior of chronic headache, particularly chronic migraine, during pregnancy.
      Collaboration between headache specialists and obstetricians is needed to promote
      research and education for the optimal management of headache during pregnancy.

PMID- 18325296
TI  - Update on the prophylaxis of migraine.
AB  - Migraine prophylaxis is a stepwise procedure with lifestyle advice followed by
      consideration of medications. Patients should be advised to try to maintain a
      regular lifestyle, with regular sleep, meals, exercise, and management of stress,
      perhaps through relaxation techniques or other ways that are sensible for them.
      If this regimen does not adequately control their migraines, preventatives are
      indicated. Patients can choose between evidence-based nutraceuticals such as
      riboflavin, feverfew, butterbur, or coenzyme Q10, or more traditional
      pharmacotherapeutics. Medicine choices are somewhat limited by what is available
      in each country, but from the full range, the medicines of first choice are beta
      adrenoceptor blockers, flunarizine, topiramate, and valproic acid. Beta
      adrenoceptor blockers are particularly useful in patients also suffering from
      hypertension or tachycardia. Following recent studies, topiramate has become a
      first choice for episodic as well as chronic migraine. It is the only
      prophylactic drug that may lead to weight loss, but it is sometimes associated
      with adverse cognitive effects. Valproic acid and flunarizine also have very good
      prophylactic properties. However, valproic acid is often associated with adverse
      effects, and flunarizine is unavailable in many countries, including the United
      States. If sequential monotherapies are ineffective, combinations of first-line
      drugs should be tried before advancing to drugs of second choice, which are
      associated with more adverse effects or have less well-established prophylactic
      properties. Amitriptyline should be used carefully because of its anticholinergic
      effects, although it is useful in comorbid tension-type headache, depression, and
      sleep disorders. Methysergide is very effective, but it has been supplanted or
      even made unavailable in many countries because of its well-described association
      with retroperitoneal fibrosis. Pizotifen has a slightly better safety profile but
      is unavailable in the United States. Aspirin is particularly useful in patients
      needing platelet inhibitors for other medical conditions, but the risk of
      gastrointestinal bleeding must be considered. The prophylactic properties of
      magnesium, riboflavin, and coenzyme Q10 are low at best, but their lack of severe
      adverse effects makes them good treatment options. Magnesium may be particularly
      useful during pregnancy. Lisinopril and candesartan were shown to be effective in
      single trials and are preferable in patients with hypertension. Acupuncture may
      be another alternative; although controlled trials have failed to differentiate
      its effect from placebo, it is at least innocuous. Botulinum toxin A is not
      effective in the prophylaxis of episodic migraine.

PMID- 18325297
TI  - Update on the therapy of the trigeminal autonomic cephalalgias.
AB  - The treatment of trigeminal autonomic cephalalgias requires very careful
      attention to clinical aspects. It is important to spend enough time assessing the
      patient to arrive at an accurate diagnosis. Identifying trigger factors (eg,
      alcohol), when applicable, is part of the therapy, as behavior modifications may
      be necessary. Cluster headache treatment should never be delayed; patients should
      be able to visit the clinic within 48 hours to expedite medication initiation.
      Abortive therapy typically is best achieved with nasal oxygen, sumatriptan
      injections, or both. Typically, a steroid taper is begun and will be continued
      for a few days. A prophylactic agent such as verapamil or topiramate also is
      initiated immediately and will be taken for a period slightly beyond the expected
      duration of the last cluster period before an attempt is made to taper it off.
      For chronic cluster headache, lithium carbonate is recommended after a few weeks
      if these other treatments have failed. If more than three regimens of medical
      therapy fail, patients should be considered for neurostimulation procedures.
      Paroxysmal hemicrania most often responds to indomethacin. Failure may be due to
      a dosage that is too low. Gastric protection should always be given, because this
      medication has a high rate of gastric complications. Short-lasting unilateral
      neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)
      remain very difficult to treat. Lamotrigine is the first recommendation. Overall,
      one of the most crucial aspects of the management of patients with these
      disabling headache syndromes is patient education regarding what their disorder
      is and the reasoning behind the therapeutic options offered.

PMID- 18325298
TI  - Treatment of comorbidities of chronic daily headache.
AB  - The treatment of chronic daily headaches should focus not only on establishing an
      effective plan for pain therapy but also on addressing factors that may diminish
      progression from episodic headache toward chronic daily headache. These measures
      may translate into better treatment efficacy and satisfaction, as well as
      decrease the headache burden. Because episodic migraine progresses to chronic
      daily headache in some (not most) individuals, research will increasingly focus
      on identifying factors associated with progression, such as specific genetic and
      environmental risk factors, including comorbidities. Ultimately, the assessment
      of the migraine patient will include an evaluation of risk factors for
      progression. In addition to the symptom profile, evaluation will increasingly
      focus on comorbidities, ictal and interictal functional consequences of migraine,
      health-related quality of life, treatment needs, and treatment preferences.
      Estimation of the risk of progression will incorporate assessments of
      comorbidity, exposures, and eventually biomarkers. Those with high risk of
      progression will be more aggressively treated, not just to relieve current pain
      and disability but to prevent progression. Therefore, treatment will focus on
      decreasing current burden and preventing future burden.

PMID- 18325299
TI  - Sturge-weber syndrome: a unified pathophysiologic mechanism.
AB  - According to a new, unifying view of the pathogenesis of Sturge-Weber syndrome
      and related syndromes, signs and symptoms all arise from localized primary venous
      dysplasia, with effects of venous hypertension transmitted to nearby areas via
      persisting communicating venous passageways and compensatory collateral venous
      channels. Port-wine stains result from a vascular disorder rather than a neural
      disorder. Symptoms depend upon the extent and location of the venous dysplasia.
      This hypothesis is supported by published data and by original observations and
      Doppler ultrasonographic studies of orbital venous flow in patients with the
      Sturge-Weber syndrome. This new understanding of underlying pathophysiology also
      elucidates the mechanism for tissue hypertrophy. Therapies aimed at obliterating
      port-wine stains to minimize the cosmetic blemish will reduce collateral venous
      blood-flow passageways. In some instances, this reduction may worsen blood stasis
      within the brain and potentially exacerbate neurologic symptoms.

PMID- 18325300
TI  - Neuromyelitis optica.
AB  - Neuromyelitis optica (NMO, Devic's syndrome) is characterized by concurrence of
      optic neuritis and transverse myelitis, typically associated with a lesion in the
      spinal cord extending over three or more vertebral segments. It is an
      inflammatory, demyelinating central nervous system disorder, and although it is
      most commonly relapsing, it is distinct from multiple sclerosis in that it is
      more severe, tends to spare the brain, and is associated with a longitudinally
      extensive lesion on spinal cord MRI. Furthermore, NMO is associated with a highly
      specific serum autoantibody marker, NMO-IgG, which targets the water channel
      aquaporin-4. The disease follows a relapsing course in more than 90% of patients.
      The relapses account for almost all disability associated with the disease
      because a secondary progressive course is uncommon, in contrast to multiple
      sclerosis. We recommend intravenous corticosteroids for acute myelitis and optic
      neuritis relapses, followed quickly by rescue plasmapheresis for severe,
      progressive, steroid-refractory events. Overwhelming evidence supports humoral
      autoimmune mechanisms in the pathogenesis of NMO, and most available data suggest
      that systemic immunosuppression is required to prevent attacks. We recommend long
      term treatment with oral agents such as azathioprine or mycophenolate mofetil for
      patients with relatively mild disease and rituximab for those with more severe,
      recent attacks or treatment-refractory disease. We also recommend
      immunosuppression for at least 5 years in NMO-IgG seropositive patients
      presenting with a first-ever attack of longitudinally extensive transverse
      myelitis because they are at high risk for relapse or conversion to NMO.

PMID- 18325301
TI  - Treatment of Susac's Syndrome.
AB  - Susac's syndrome (SS) consists of the triad of encephalopathy, branch retinal
      artery occlusions (BRAO), and hearing loss. It usually affects women aged 20 to
      40, but men are also affected, and the age range extends from 9 to 72 years. It
      tends to be unrecognized, even in major academic centers. The complete triad may
      not be present at the onset, which makes diagnosis more difficult. However, since
      this disorder is treatable, early diagnosis is important. The encephalopathy is
      usually associated with headaches, multifocal neurologic manifestations, and
      psychiatric features (particularly paranoia). MRI shows a white matter
      disturbance that is frequently confused with multiple sclerosis and acute
      disseminated encephalomyelitis. During the encephalopathy, the corpus callosum is
      always affected and shows central involvement--small to large "snowballs" and
      linear defects, "spokes." As the acute changes (microinfarcts) resolve, central
      callosal "holes" develop, a pathognomonic finding. The deep gray matter (70%) and
      leptomeninges (33%) also may be involved. Dilated fundus examination will reveal
      branch retinal artery occlusions. Fluorescein angiography may disclose
      pathognomonic staining of the arterioles proximal to the occlusions and of
      nonoccluded arterioles. The cochlear hearing loss, sometimes associated with
      vertigo, is usually bilateral, and deafness becomes a major disabling problem.
      Brain biopsies, anatomic observations, and responses to immunosuppressive therapy
      suggest that SS represents an autoimmune endotheliopathy in the microvasculature
      of the brain, retina, and cochlea. Treatment requires immunosuppression. High
      dose corticosteroid therapy is the mainstay, but additional therapies such as
      intravenous immunoglobulin, mycophenolate mofetil, and cyclophosphamide are often
      necessary. Rituximab is the newest therapy to consider. Treatment should be
      prompt, aggressive, and sustained to avoid the dreaded residuals of dementia,
      deafness, and blindness.

PMID- 18325302
TI  - Identification and treatment of arterial thrombophilia.
AB  - Once the diagnosis of a thrombophilic state has been established, management must
      include one or more strategies designed to attenuate thrombotic risk and the
      likelihood of clinical events. In the case of drug-induced arterial thrombosis
      provoked by oral contraceptives, hormone replacement therapy, heparinoids,
      cocaine, or thienopyridine-related thrombotic thrombocytopenic purpura (TTP), the
      offending agent should be discontinued immediately. Anticoagulant therapy and
      platelet-directed therapies, either alone or in combination, should be considered
      for patients experiencing a single arterial or venous thrombosis (secondary
      prevention), with treatment duration determined by diagnostic studies and the
      persistence of a prothrombotic state. Other specific therapies should be directed
      at the underlying thrombophilic disorder. These treatments include direct
      thrombin inhibitors such as argatroban for heparin-induced thrombocytopenia
      (HIT), myelosuppressive drugs such as hydroxyurea for essential thrombocytosis,
      plasma exchange for thrombotic thrombocytopenic purpura, and phlebotomy for
      polycythemia vera. Additionally, the treating physician must seek input early
      from a hematologist or rheumatologist when managing patients with known or
      suspected HIT, TTP, and myeloproliferative disorders, or the antiphospholipid
      syndrome, respectively. This interdisciplinary interface is critical to ensure an
      optimal outcome when treating patients with arterial thrombophilia.

PMID- 18325303
TI  - Antiplatelet therapy in the era of late stent thrombosis.
AB  - Drug-eluting stents (DES) are the treatment of choice for obstructive coronary
      artery disease when percutaneous intervention is feasible. Although there are
      concerns regarding increased incidence of stent thrombosis, subsequent myocardial
      infarction, and death in patients receiving DES, careful analysis of large
      randomized trials has shown that risk of stent thrombosis with both bare metal
      stents (BMS) and DES is small. However, late stent thrombosis seems to occur more
      frequently with DES and seems to be closely associated with the discontinuation
      of dual antiplatelet therapy with aspirin and a thienopyridine derivative
      (usually clopidogrel). Before placing a DES in a patient, the interventional
      cardiologist must ensure that there are no conditions under which a patient or
      physician may have to discontinue dual antiplatelet therapy within a year after
      stent placement. If the cardiologist anticipates premature discontinuation of
      thienopyridine and aspirin therapy, his or her alternative is to place a BMS or
      recommend bypass surgery. If a situation arises in which dual antiplatelet
      therapy may have to be interrupted (eg, emergency or semi-elective surgery), it
      is strongly recommended that the treating physician consult a cardiologist and
      follow published guidelines.

PMID- 18325304
TI  - Slowing the progression of aortic stenosis.
AB  - Aortic stenosis (AS) is the most frequent valvular heart disease in the Western
      world. The only definitive treatment for this disorder is surgical replacement of
      the aortic valve. Recent histopathologic studies have provided important insights
      into the pathogenesis of calcific AS. These results suggest that this disease
      develops as the result of an active disease process at the cellular and molecular
      levels that shares many similarities with vascular atherosclerosis, ranging from
      endothelial dysfunction to, ultimately, calcification. In this review, we discuss
      the cellular and molecular mechanisms, natural history, diagnosis, and
      therapeutic options, including the potential for medical therapies, for the
      treatment of AS.

PMID- 18325305
TI  - Management of the metabolic syndrome in cardiovascular disease.
AB  - The main components of the metabolic syndrome (MS) are abdominal obesity,
      atherogenic dyslipidemia, raised blood pressure, insulin resistance with or
      without glucose intolerance, and proinflammatory and prothrombotic states. The
      clustering of these metabolic risk factors significantly increases the risk of
      type 2 diabetes and promotes vascular endothelial dysfunction, inflammation, and
      increased oxidative stress. The net result is an increase in the risk of
      atherosclerotic cardiovascular disease. Therefore, management of MS is of utmost
      importance, especially considering its rapidly increasing prevalence in a
      population with rising obesity rates and its significant cardiovascular
      implications. The primary management of this syndrome involves the correction of
      the underlying risk factors--obesity, physical inactivity, and an atherogenic
      diet--with lifestyle modifications including increased physical activity and
      dietary modification. Smoking cessation also should be encouraged. However,
      pharmacologic therapies are often required to address cardiovascular risk
      factors. These agents can be categorized broadly into 1) anorectic agents, 2)
      insulin-sensitizing agents, 3) statins, and 4) renin-angiotensin system
      antagonists. Emerging therapies include adipokines, endocannabinoid inhibitors,
      and metabolic modulators, such as perhexiline and trimetazidine. To date, these
      therapies have not been shown to normalize the metabolic and cardiovascular
      burden of MS, and there still is no single therapeutic agent for its management.

PMID- 18325306
TI  - Treatment options for patients with coronary artery disease identified as high
      risk by T-wave alternans testing.
AB  - Risk stratification for primary prevention of sudden cardiac death (SCD) remains
      a major challenge in cardiology. The utility of T-wave alternans (TWA) as a
      marker of risk of life-threatening ventricular tachycardia and fibrillation is
      supported by two decades of basic and clinical research. Both frequency- and time
      domain methods have been developed, validated, and made available in clinical
      practice. A principal application of TWA testing has been to improve assessment
      of patients with depressed left ventricular ejection fraction (EF; </= 40%) who
      are considered for implantable cardioverter-defibrillator (ICD) implantation for
      primary prevention of SCD. TWA has been most useful in identifying patients who
      are unlikely to benefit from ICD therapy. Although patients with low EF should
      remain an important focus, the absolute number of SCD events is far greater among
      post-myocardial infarction patients with relatively preserved EF, even though the
      incidence of SCD in this population is low. Recent studies suggest that TWA
      testing is predictive in this population as well. Absolute quantification of TWA
      rather than binary classification into "normal" or "abnormal" appears to be
      valuable in more finely stratifying the magnitude of arrhythmic risk.
      Longitudinal testing may be warranted in certain populations, although the
      optimum interval remains to be determined. Combining TWA with noninvasive markers
      of autonomic function, such as heart rate turbulence, may further increase
      predictive accuracy. Future development will likely expand the role of TWA
      testing with routine exercise and ambulatory electrocardiographic monitoring to
      screen lower-risk populations and to guide medical and device-based therapy.

PMID- 18325307
TI  - New strategies for cardiopulmonary resuscitation.
AB  - Sudden death claims hundreds of thousands of lives each year in the United
      States. Emergency resuscitation efforts are successful in only about 6% of all
      out-of-hospital arrests. In light of the poor survival rate, innovative research
      is reexamining the practice of cardiopulmonary resuscitation. Basic life support
      (BLS), with its stepwise management of airway, breathing, circulation, and
      defibrillation, is far from a rudimentary procedure. Each step has been
      challenged and changed in recent years, reflecting ongoing resuscitation research
      into the mechanisms, efficacy, and practical aspects of delivery of these
      interventions. Recommended modifications to BLS techniques have resulted in
      increased survival rates. Therefore, health professionals need to stay current
      with the latest guidelines through literature reviews and frequent
      recertification.

PMID- 18325308
TI  - Repairing damaged myocardium: evaluating cells used for cardiac regeneration.
AB  - Cellular cardiomyoplasty has raised hopes of regenerating mechanical function in
      the heart. Several cell sources have been investigated for their ability to
      repair the damaged heart, providing reason for optimism. Multiple mechanisms have
      been proposed for the beneficial effects of the delivered cells; however, true
      reversal of cardiac damage implies the generation of new contractile myocytes.
      The assessment of a cell's ability to regenerate contractile cells requires a
      defined set of criteria that, if met, define success. Here we review data from
      the four primary players in cellular cardiomyoplasty (skeletal myoblasts, bone
      marrow cells, embryonic stem cells, and resident cardiac stem cells) and assess
      their potential to differentiate into contractile myocytes as indicated by their
      ability to meet such specified milestones. Both animal studies and clinical
      trials suggest that current experimental approaches to cellular cardiomyoplasty
      yield short-term improvement, although it may be independent of cell type used.
      However, the mechanisms underlying this salutary effect, as well as its
      persistence in the longer term, have remained elusive.

PMID- 18325309
TI  - New approaches to the concept of primary prevention of atherosclerosis.
AB  - Our understanding of the etiology of atherosclerosis and the mechanisms by which
      conventional cardiovascular risk factors cause disease is incomplete.
      Atherosclerosis may be regarded as a process of continuous injury and abnormal
      repair. The diagnosis and treatment of the disease should be targeted to the
      various stages of this process, from the early stages of vascular injury to the
      stabilization of the vulnerable plaque. Several novel concepts in atherosclerosis
      have been elucidated in the past two decades. Novel biomarkers and imaging
      techniques for early subclinical atherosclerotic lesions may facilitate earlier
      primary prevention. Future primary prevention of atherosclerosis should
      incorporate these novel concepts for creation of individualized risk profiles and
      therapies.

PMID- 18325310
TI  - Cardiac magnetic resonance imaging in patients with coronary disease.
AB  - Cardiac magnetic resonance (CMR) has emerged as a versatile noninvasive tool for
      the comprehensive evaluation of patients with suspected or established coronary
      artery disease (CAD). In a single imaging session, CMR can assess left
      ventricular anatomy and function, myocardial perfusion, viability, and coronary
      luminal stenosis. Using specific pulse sequences, left ventricular global and
      regional function can be assessed by cine CMR at rest and in response to
      inotropic stress; first-pass perfusion quantified by vasodilator stress;
      myocardial viability evaluated by delayed enhancement imaging and also by
      functional reserve; and coronary artery stenosis assessed by angiography. All
      these modalities can be achieved with high spatial resolution and image contrast,
      without exposure to ionizing radiation, and within a reasonable time frame of
      about 1 hour of scan time. Also, the imaging planes can be programmed to provide
      identical views of the heart for each type of image, thereby facilitating
      intermodality comparisons. There is early but accumulating evidence that the
      accuracy and prognostic values of many of these modalities are comparable or
      superior to radionuclide scintigraphy and echocardiography in head-to-head
      studies. Current limitations unique to CMR include the inability to perform
      exercise stress testing inside the CMR suite and exclusion of patients with
      indwelling metallic devices such as defibrillators and pacemakers. Despite these
      limitations, CMR is unique in its multifaceted approach that can be specifically
      tailored to the clinical question at hand, making it arguably the best tool for
      the diagnosis and management of CAD. With the rapid pace of advancement in CMR
      hardware and pulse sequence technologies, the clinical use of this powerful
      technique is likely to grow even greater in this area.

PMID- 18325311
TI  - Treating patients with non-STEMI: stent the culprit artery only or address all
      lesions?
AB  - Non-ST segment elevation myocardial infarction (non-STEMI) is a common
      presentation of the acute coronary syndrome (ACS) spectrum. Currently, the
      recommended treatment option is an invasive approach with angiography plus
      coronary revascularization to treat the culprit lesion. However, unlike in STEMI-
      in which the culprit lesion can be easily identified--in non-STEMI identifying
      the culprit lesion is difficult. Therefore, some have advocated for a more
      definitive approach to addressing all severe lesions in patients presenting with
      non-STEMI. The current European guidelines for percutaneous coronary intervention
      (PCI) for multivessel versus culprit-only stenting state that "the decision to
      perform either culprit vessel or complete revascularization can be made on an
      individual basis," whereas the American College of Cardiology/American Heart
      Association guidelines for multivessel PCI in patients presenting with ACS
      recommend that "it be performed when there is a high likelihood of success and a
      low risk of morbidity and the vessels to be dilated subtend a moderate or large
      area of viable myocardium and have high risk by noninvasive testing." Although
      lesions and coronary anatomies are each unique and the risk and benefit of
      coronary intervention to each lesion should be carefully examined, we recommend
      stenting the culprit lesion and other severe lesions after careful consideration,
      in a staged fashion if necessary. If the severity of nonculprit lesions is in
      question, fractional flow reserve or intravascular ultrasound should be
      considered.

PMID- 18325312
TI  - Update on vena cava filters.
AB  - Inferior vena cava (IVC) filter placement has increased dramatically over the
      past two decades. Filters are indicated to prevent pulmonary embolism in patients
      with venous thromboembolism (VTE) and a contraindication to anticoagulation or a
      complication of anticoagulation. Some of this increased use is the result of
      expanding relative indications for filter placement, including placement for
      primary prophylaxis. The US Food and Drug Administration has approved 11 filters
      for permanent deployment, two of which--the Gunther-Tulip (Cook Medical,
      Bloomington, IN) and the OptEase (Cordis Endovascular, Miami Lakes, FL)--are
      optionally retrievable. Once anticoagulation is deemed safe, all patients should
      be fully anticoagulated to prevent propagation and recurrent thromboembolism.
      Complications related to IVC filters include procedure-related issues, device
      complications, and secondary VTE. Therefore, the decision regarding filter
      placement and/or retrieval must be individualized.

PMID- 18325313
TI  - Median arcuate ligament syndrome.
AB  - Median arcuate ligament syndrome (MALS) can cause a range of symptoms, including
      abdominal pain, nausea, vomiting, and weight loss. Because all patients have some
      degree of celiac artery compression by the median arcuate ligament (MAL), it may
      be difficult to discern which patients have a pathologic compression. Based on
      the multiple theories of MALS etiology, it is unlikely that we know the true
      cause of this syndrome. In fact, there are many physicians who question the
      validity of the diagnosis of MALS. Before offering intervention for MALS, a
      thorough gastrointestinal evaluation should be performed, including consideration
      of diagnostic temporary percutaneous celiac ganglion block. Patients who are on
      chronic narcotics preoperatively have a lower likelihood of postoperative symptom
      relief and therefore should be evaluated by a pain specialist preoperatively. The
      most reliable treatment comprises open surgical treatment with division of the
      MAL, removal of surrounding celiac ganglion, evaluation of the celiac artery with
      pressure measurements or ultrasound, and celiac artery reconstruction if
      indicated. Laparoscopic and endovascular interventions are novel treatments and
      may be considered in select patients who cannot undergo an open surgical
      procedure.

PMID- 18325314
TI  - Heparin-induced thrombocytopenia: 2008 update.
AB  - Unfractionated heparin (UFH) and the low molecular weight heparin (LMWH)
      preparations are two of the most commonly prescribed medications in the hospital,
      and indications for their use are increasing. An increasingly recognized untoward
      effect of either UFH or LMWH is heparin-induced thrombocytopenia (HIT), a
      transient, prothrombotic condition that may result in venous or arterial
      thrombosis and amputation or death. This immune-mediated process generally
      develops within 4 to 14 days of administration, although it may occur more
      rapidly if there has been a recent exposure; it may even occur days to weeks
      after UFH or LMWH has been discontinued. Although once considered necessary for
      the diagnosis of HIT, thrombocytopenia is no longer essential. A 50% reduction in
      the platelet count from pre-heparin treatment levels is now considered a more
      specific finding. Prompt recognition, discontinuation of the offending agent, and
      initiation of an alternative anticoagulant are essential for prevention and/or
      treatment of these potentially devastating complications.

PMID- 18325315
TI  - Pernio (chilblains).
AB  - Pernio is a vasospastic disorder that affects unprotected skin regions of
      individuals exposed to nonfreezing, damp cold. It may be idiopathic or associated
      with other systemic diseases, particularly cryopathies and lupus erythematosus.
      Acute pernio manifests several hours following exposure, whereas chronic pernio
      may persist even after the cold season has long ended. The pathophysiology is
      complex and related to patient and environmental factors. Pernio is diagnosed by
      clinical features. There are no characteristic histopathologic features that
      confirm the diagnosis, but biopsy of affected areas may exclude the presence of
      other disorders. Sequelae include superinfection, depigmentation, and scarring.
      Treatment involves rewarming of the whole body and avoidance of further exposure
      to cold. The use of the dihydropyridine calcium channel blocker nifedipine
      promotes faster healing and prevents recurrence.

PMID- 18325316
TI  - Treatment of venous thrombosis at unusual sites.
AB  - The literature is filled with randomized controlled trial data to guide most
      steps in managing patients with deep venous thrombosis of the extremities or
      pulmonary embolism. Venous thrombosis, however, is not limited to these locations
      and may involve the cerebral venous sinuses, renal veins, splanchnic veins, and
      ovarian veins. The causes of these thrombi are often unique to the venous
      segments involved and typically stem from pathologies of the organs supplied by
      these veins. Very little randomized controlled trial data exist to guide therapy
      for these atypical venous thrombi. Treatment should focus on correcting the
      underlying disease and relieving venous congestion of the involved organ while
      preserving organ functionality. Although natural history data are limited,
      recurrence rates for these atypical venous thrombi appear to be relatively low.
      Indefinite secondary anticoagulant prophylaxis is therefore primarily dictated by
      the congenital or acquired pathology precipitating the event.

PMID- 18325317
TI  - Raynaud's phenomenon.
AB  - Treatment of Raynaud's phenomenon in any one individual depends on the severity
      of symptoms and whether or not there is an underlying disease process requiring
      specific intervention. Many patients with primary (idiopathic) Raynaud's
      phenomenon respond well to treatment with general measures, perhaps with the
      addition of a calcium channel blocker. Conversely, others with underlying
      structural vascular abnormality (as occurs in connective tissue diseases such as
      systemic sclerosis ) are often refractory to treatment and may progress to
      irreversible tissue injury, sometimes with gangrene. Because these patients are
      the most challenging and because a large proportion of the research into
      Raynaud's phenomenon has been conducted in patients with SSc-spectrum disorders,
      much of this review is weighted toward them. The key principles of management are
      removal/treatment of any triggering factor/underlying cause, general (nondrug)
      measures, drug treatment, and surgery, although the last is rarely indicated. New
      insights into pathogenesis have led, and continue to lead, to new approaches to
      treatment, including endothelin-1 receptor antagonism and nitric oxide
      supplementation.

PMID- 18325318
TI  - New strategies in the medical treatment of carotid artery disease.
AB  - Most patients with ischemic stroke or transient ischemic attack are screened for
      internal carotid artery stenosis. Although it is important to identify candidates
      for endarterectomy or stenting, the clinician must realize that most patients are
      not candidates for revascularization. Therefore, medical therapy remains the
      cornerstone of treatment. In this article, current thinking on medical therapy
      for carotid atherosclerosis is outlined, including aggressive use of statins,
      targeted blood pressure lowering, and antithrombotic therapy. Implementation of
      these therapies will likely reduce the need for revascularization procedures in
      the future.

PMID- 18325319
TI  - Takayasu's arteritis.
AB  - Takayasu's arteritis is a rare disease that causes arterial inflammation with
      resulting stenosis or aneurysm of affected vessels. It primarily affects young
      females and has a predilection for the aorta, its primary branches, and the
      pulmonary arteries. Patients may present with symptoms of organ ischemia, such as
      stroke or claudication, or with signs of arterial stenosis, such as absent pulses
      or asymmetric blood pressures. Most patients require chronic immunosuppressive
      therapy to control inflammation. The foundation of therapy is glucocorticoids,
      which are often used in combination with other immunosuppressive agents, such as
      methotrexate, azathioprine, or mycophenolate mofetil. The goal of systemic
      therapy is to induce and maintain disease remission, often defined as the absence
      of new arterial lesions, lack of systemic symptoms, and ability to taper
      prednisone to less than 10 mg/d. Promising results have been seen with the use of
      agents directed against tumor necrosis factor in patients who have failed to
      maintain remission with standard therapies. Revascularization procedures such as
      percutaneous transluminal angioplasty (PTA) or bypass grafting are reserved for
      patients who have critical organ ischemia or severe extremity claudication.
      Bypass grafting has a lower restenosis rate than PTA and is the preferred method
      of restoring blood flow to affected organs. Frequent laboratory testing is
      recommended to monitor for drug toxicity and signs of disease relapse. At each
      clinic visit, physicians should auscultate for bruits over primary arterial
      branches and evaluate for asymmetry between arm and leg blood pressures. Biannual
      radiographic imaging with magnetic resonance or CT angiography is helpful to
      examine for evidence of new aortic aneurysms or arterial stenoses.

PMID- 18325320
TI  - Pseudoaneurysm: a review.
AB  - Pseudoaneurysms may arise from any artery in the human body. Most commonly found
      to involve the femoral artery after angiography, the presentation may vary from
      being clinically silent to a life-threatening emergency scenario. Recognition of
      this condition and treatment largely depend on the hemodynamic stability and
      anatomy of the pseudoaneurysm. Advances in treatment have enabled nonsurgical
      therapy in a significant number of cases. Ultrasound-guided thrombin injection is
      a fairly easy and effective treatment option. Other endovascular approaches, such
      as stent graft repair and coil embolization, are also available. Endovascular
      techniques play an important role in treating pseudoaneurysms arising from the
      aorta as a result of blunt trauma or previous aortic surgery. It is important to
      recognize the indications for surgery to avoid delay in the management of this
      potentially limb- or life-threatening condition.

PMID- 18325321
TI  - Cellular prion protein in mammary gland and milk fractions of domestic ruminants.
AB  - The present study shows that PrP(c) is expressed in the mammary gland and milk
      fractions of domestic ruminants in a species-specific manner. By applying
      immunohistochemistry, Western blot and ELISA, clear expression differences
      between bovine, ovine and caprine mammary gland, skimmed milk, acid whey and
      cream could be demonstrated, the highest relative PrP(c) levels being associated
      with the cream fraction. In the bovine gland PrP(c) was preferentially detectable
      at the basolateral surface of mammary gland epithelial cells, whereas in ovine
      and caprine samples the prion protein was more homogeneously distributed.
      Moreover, in ovine and caprine bovine mammary gland epithelial cells, apocrine
      secretory vesicles were strongly stained. Ovine and caprine milk proved to
      contain PrP(c) in all fractions with an additional truncated form at 12kDa in
      Western blot. This truncated isoform is the predominate one in caprine acid whey.
      These results support the hypothesis that the apocrine secretion mode of milk fat
      globules is a major way of PrP(c) transport into the milk.

PMID- 18325322
TI  - Chorion gene activation and repression is dependent on BmC/EBP expression and
      binding to cognate cis-elements.
AB  - From the different cis-elements clustered on silkmoth chorion gene promoters,
      C/EBP binding sites predominate. Their sequence composition and dispersal vary
      amongst promoters of diverse developmental specificity. Occupancy of these sites
      by BmC/EBP was examined through Southwestern and ChIP assays modified to suit
      ovarian follicular cells. For the genes studied, binding of BmC/EBP coincided
      with the respective stages of transcriptional activation. However, the factor was
      reloaded on promoter sequences long after individual gene repression.
      Furthermore, suppression of BmC/EBP transcription in developing follicles
      resulted in de-regulation of chorion gene expression. A biphasic function of
      BmC/EBP, according to which it may act as both an activator and a repressor
      during silkmoth choriogenesis, is considered under the light of the presented
      data.

PMID- 18325323
TI  - Nephrotoxic cell death by diclofenac and meloxicam.
AB  - The nephrotoxicity of diclofenac, a non-steroidal anti-inflammatory drug that
      inhibits both isoforms of cyclooxygenase (COX) has been reported to be fatal to
      vultures but this was not so with meloxicam which is COX-2 selective. Our study
      showed that diclofenac was more toxic than meloxicam to both the proximal tubular
      LLC-PK1 cells and the distal tubular Madin-Darby canine kidney type II (MDCKII)
      cells, and that LLC-PK1 cells were more susceptible. Exposure of MDCKII cells to
      meloxicam caused activation of caspase-9/-3 and release of cytochrome c. These
      observations together with a positive annexin V-FITC staining implicate an
      intrinsic mitochondrial cell death pathway by apoptosis. Diclofenac-treated
      MDCKII cells on the other hand showed extensive propidium iodide staining,
      suggestive of cell death by necrosis. The mode of cell death in LLC-PK1 cells was
      however less well-defined with positive annexin V-FITC staining but minimal
      increase in caspase-3 activity alluding to a caspase-independent pathway.

PMID- 18325324
TI  - The nitric oxide-sensitive p21Ras-ERK pathway mediates S-nitrosoglutathione
      induced apoptosis.
AB  - p21Ras protein plays a critical role in cellular signaling that induces either
      cell cycle progression or apoptosis. Nitric oxide (NO) has been consistently
      reported to activate p21Ras through the redox sensitive cysteine residue (118).
      In this study, we demonstrated that the p21Ras-ERK pathway regulates THP-1
      monocyte/macrophage apoptosis induced by S-nitrosoglutathione (SNOG). This was
      apparent from studies in THP-1 cells expressing NO-insensitive p21Ras
      (p21Ras(C118S)) where the pro-apoptotic action of SNOG was almost abrogated.
      Three major MAP kinase pathways (ERK, JNK, and p38) that are downstream to p21Ras
      were investigated. It was observed that only the activation of ERK1/2 MAP kinases
      by SNOG in THP-1 cells was attributable to p21Ras. The inhibition of the ERK
      pathway by PD98059 markedly attenuated apoptosis in SNOG-treated THP-1 cells, but
      had a marginal effect on SNOG-treated THP-1 cells expressing NO-insensitive
      p21Ras. The inhibition of the JNK and p38 pathways by selective inhibitors had no
      marked effects on the percentage of apoptosis. The induction of p21Waf1
      expression by SNOG was observed in THP-1 cells harboring mutant and wild-type
      p21Ras, however in cells expressing mutant Ras, the expression of p21Waf1 was
      significantly attenuated. The treatment of THP-1 cells expressing wild-type
      p21Ras with PD98059 resulted in significant attenuation of p21Waf1 expression.
      These results indicate that the redox sensitive p21Ras-ERK pathway plays a
      critical role in sensing and delivering the pro-apoptotic signaling mediated by
      SNOG.

PMID- 18325325
TI  - Pleurocidin-derived antifungal peptides with selective membrane-disruption
      effect.
AB  - Pleurocidin (Ple) is a peptide derived from the winter flounder. In our previous
      study, we reported the antifungal effect of Ple and its mode of action. To
      develop novel antifungal peptides useful as therapeutic agents, two analogs, with
      amino acid substitutions, were designed to decrease the net hydrophobicity by Arg
      (R) or Ser (S)-substitution at the hydrophobic face of Ple without changing the
      amphipathic structure. By substituting Ser, the hydrophobicity of the peptide
      (anal-S) was decreased, and by substituting Arg, though the hydrophobicity of the
      peptide (anal-R) was decreased, the cationicity of this peptide was increased. CD
      measurements showed the substitution of Arg or Ser decrease the alpha-helical
      conformation of analog peptides. Studies with analog peptides have shown
      decreases in hydrophobicity and alpha-helicity do not affect antifungal activity
      but decrease hemolytic activity. These results suggest that highly hydrophobic
      and alpha-helical natures are not desirable in the design of antimicrobial
      peptides.

PMID- 18325326
TI  - Methylation of a conserved intronic CpG island of mouse SF-1 is associated with
      cell-specific expression of SF-1 in a culture system but not with tissue-specific
      expression.
AB  - The mechanism for the steroidogenic tissue or cell-specific expression of SF-1
      has not been well clarified. We examined whether the methylation status of a
      large CpG island in the first intron of mouse SF-1 gene is associated with the
      expression level of SF-1 in cultured cells and in tissues. The island consists of
      three small islands (ICI-1, ICI-2, and ICI-3). In cultured adrenocortical Y-1
      cells and in Leydig tumor cells, I-10, that both express high levels of SF-1, the
      upstream region of ICI-2, ICI-2-1, was clearly hypomethylated compared to
      cultured mouse bone marrow cells that do not express SF-1. However, this
      methylation status was not clearly associated with the tissue-specific expression
      of SF-1, in either adult or during development. These results suggest that
      methylation of ICI-2-1of SF-1 may partly determine the level of SF-1 expression
      at the cellular level, but may not be essential at the tissue level.

PMID- 18325327
TI  - Caspase-dependent cleavage of BAG3 in proteasome inhibitors-induced apoptosis in
      thyroid cancer cells.
AB  - Proteasome inhibitors are emerging as effective drugs for the treatment of
      relapsed/refractory multiple myeloma and possibly some solid tumors. Bcl-2
      associated athanogene 3 (BAG3) is a survival protein that has been shown to be
      stimulated during cell response to stressful conditions, such as exposure to high
      temperature, heavy metals. We have recently demonstrated that BAG3 is also
      induced by proteasome inhibitors at the transcriptional level and the induction
      of BAG3 by proteasome inhibition is antiapoptotic. Here, we demonstrated that
      although proteasome inhibitors triggered similar upregulation of BAG3 transcript
      in sensitive and insensitive thyroid cancer cells, persistent increase of BAG3
      protein was detected in insensitive cells, whereas less increase or even decrease
      was observed in sensitive cells. Notably, decrease of BAG3 protein was associated
      with the appearance of a BAG3 fragment of approximately 40kDa, which appeared to
      be caspase-dependent. Therefore, caspase-dependent cleavage of BAG3 might
      facilitate apoptosis in sensitive cells.

PMID- 18325328
TI  - Siglec-9 enhances IL-10 production in macrophages via tyrosine-based motifs.
AB  - We examined whether Siglec-9 modulates cytokine production in the macrophage cell
      line RAW264. Cells expressing Siglec-9 produced low levels of tumor necrosis
      factor (TNF)-alpha upon stimulation with lipopolysaccharide, peptidoglycan,
      unmethylated CpG DNA, and double-stranded RNA. On the other hand, interleukin
      (IL)-10 production was strongly enhanced in Siglec-9-expressing cells. Similar
      activities were also exhibited by Siglec-5. However, the up-regulation of IL-10
      as well as the down-regulation of TNF-alpha was abrogated when two tyrosine
      residues in the cytoplasmic tail of Siglec-9 were mutated to phenylalanine. A
      membrane proximal ITIM mutant of Siglec-9 did not enhance IL-10 production but
      partly inhibited TNF-alpha production, indicating diverse regulation mechanisms
      of TNF-alpha and IL-10. Siglec-9 also enhanced the production of IL-10 in the
      human macrophage cell line THP-1. These results demonstrate that Siglec-9
      enhances the production of the anti-inflammatory cytokine IL-10 in macrophages.

PMID- 18325329
TI  - New polymorphic mtDNA restriction site in the 12S rRNA gene detected in Tunisian
      patients with non-syndromic hearing loss.
AB  - The 12S rRNA gene was shown to be a hot spot for aminoglycoside-induced and non
      syndromic hearing loss since several deafness-associated mtDNA mutations were
      identified in this gene. Among them, we distinguished the A1555G, the C1494T and
      the T1095C mutations and C-insertion or deletion at position 961. One hundred
      Tunisian patients with non-syndromic hearing loss and 100 hearing individuals
      were analysed in this study. A PCR-RFLP analysis with HaeIII restriction enzyme
      showed the presence of the A1555G mutation in the 12S rRNA gene in only one out
      of the 100 patients. In addition, PCR-RFLP and radioactive PCR revealed the
      presence of a new HaeIII polymorphic restriction site in the same gene of 12S
      rRNA site in 4 patients with non-syndromic hearing loss. UVIDOC-008-XD analyses
      showed the presence of this new polymorphic restriction site with a variable
      heteroplasmic rates at position +1517 of the human mitochondrial genome. On the
      other hand, direct sequencing of the entire mitochondrial 12S rRNA gene in the
      100 patients and in 100 hearing individuals revealed the presence of the A750G
      and A1438G polymorphisms and the absence of the C1494T, T1095C and 961insC
      mutations in all the tested individuals. Sequencing of the whole mitochondrial
      genome in the 4 patients showing the new HaeIII polymorphic restriction site
      revealed only the presence of the A8860G transition in the MT-ATP6 gene and the
      A4769G polymorphism in the ND2 gene.

PMID- 18325330
TI  - ZIFIBI: Prediction of DNA binding sites for zinc finger proteins.
AB  - The cis-regulatory region of target genes is key elements in the transcriptional
      regulation of gene expression. Many of these cis-regulatory regions have not been
      identified by either biological experiments or computational methods. Recently, a
      few additional C(2)H(2) zinc finger transcription factor binding sites have been
      discovered. The majority of the zinc finger binding sites, however, are still
      unknown. In this study, we used publically available data to evaluate possible
      interaction patterns between nucleotides and the amino acids of zinc finger
      domains. We calculated the most probable state path of three nucleotides
      sequences using a Hidden Markov Model (HMM). We used these computations to
      predict C(2)H(2) zinc finger transcription factor binding sites in cis-regulatory
      regions of their target genes (http://bioinfo.hanyang.ac.kr/ZIFIBI/frameset.php).

PMID- 18325332
TI  - The MTP -493TT genotype is associated with peripheral arterial disease: results
      from the Linz Peripheral Arterial Disease (LIPAD) Study.
AB  - OBJECTIVES: Microsomal triglyceride transfer protein (MTP) transfers lipids into
      apoprotein B-containing lipoproteins for secretion from liver, intestine, and
      heart. We hypothesized the -493T single nucleotide polymorphism in the MTP
      promoter region to be associated with altered lipoprotein levels and with
      presence of peripheral arterial disease (PAD). DESIGN AND METHODS: 433 patients
      with symptomatic PAD and 433 controls matched for sex and age from the Linz
      Peripheral Arterial Disease (LIPAD) study were genotyped cross-sectionally for
      the -493T single nucleotide polymorphism in the promoter region of the MTP gene.
      RESULTS: The frequency of the -493T allele in patients with PAD was 0.320,
      whereas it was 0.255 in controls (p<0.001). The MTP -493TT genotype was
      independently associated with PAD, even after adjustment for LDL cholesterol. The
      odds ratio of the -493TT MTP genotype for PAD was 3.18 (95% CI, 1.76-5.71) when
      adjusted for current smoking, arterial hypertension, LDL cholesterol,
      triglycerides, glycohemoglobin, C-reactive protein, and homocysteine.
      Furthermore, we found an association between the MTP promoter polymorphism and
      the apolipoprotein B-containing lipoproteins total-cholesterol (p=0.011), LDL
      cholesterol (p=0.002) and apolipoprotein B (p=0.034). CONCLUSIONS: Our results
      provide preliminary evidence for a potential role of the MTP -493TT genotype in
      the pathogenesis of PAD.

PMID- 18325333
TI  - CDK5 activator p35 downregulates E-cadherin precursor independently of CDK5.
AB  - Dysfunction of E-cadherins often results in metastasis of cancerous cells. Here
      we show that p35, a critical regulator of cyclin-dependent kinase 5 (CDK5),
      specifically depletes the precursor form of E-cadherin, but not the mature form,
      by using a precursor-specific antibody. Most intriguingly, this downregulation of
      precursor E-cadherin by p35 is unequivocally independent of CDK5. Moreover, we
      found that p35 forms complexes with E-cadherin proteins. We also found that p35
      co-expression can target E-cadherin to lysosomes and that p35-triggered
      disappearance of E-cadherin precursor can be blocked specifically by lysosomal
      protease inhibitors, indicating that p35 induces endocytosis and subsequent
      degradation of precursor E-cadherin.

PMID- 18325334
TI  - Reconstructing the single-cell-level behavior of a toggle switch from population
      level measurements.
AB  - Single-cell-level behaviors of cells are typically inferred from ensemble
      measurements. However, such inferences implicitly assume a biological version of
      ergodicity: the percentage of cells in a state is identical to the probability to
      find a cell in that state. While the ergodicity does not always hold, it has been
      rarely tested. Here, we reveal that the ergodicity does not necessarily hold even
      for simple toggle switches and that apparent stabilities of the switches are due
      to a balance between single-cell-level biased stabilities and growth rates
      differences. Therefore, verification of the ergodicity and reconstructing single
      cell-level behaviors are crucial for understanding intracellular systems.

PMID- 18325335
TI  - Affixin activates Rac1 via betaPIX in C2C12 myoblast.
AB  - Affixin/beta-parvin is an integrin-linked kinase (ILK)-binding focal adhesion
      protein highly expressed in skeletal muscle and heart. To elucidate the possible
      role of affixin in skeletal muscle, we established stable C2C12 cell line
      expressing T7-tagged human affixin (C2C12-affixin cells). Exogenous expression of
      affixin promotes lamellipodium formation where affixin, ILK alphap21-activated
      kinase (PAK)-interactive exchange factor (PIX) and betaPIX accumulate. The
      association of affixin and betaPIX was confirmed by immunoprecipitation and pull
      down assay. In C2C12-affixin cells, an increased level of activated Rac1 but not
      Cdc42 was observed, and mutant betaPIX lacking guanine nucleotide exchange factor
      activity inhibited lamellipodium formation. These results suggest that affixin is
      involved in reorganization of subsarcolemmal cytoskeletal actin by activation of
      Rac1 through alpha and betaPIXs in skeletal muscle.

PMID- 18325336
TI  - Chloroplast nitrite uptake is enhanced in Arabidopsis PII mutants.
AB  - In higher plants, the PII protein is a nuclear-encoded plastid protein that
      regulates the activity of a key enzyme of arginine biosynthesis. We have
      previously observed that Arabidopsis PII mutants are more sensitive to nitrite
      toxicity. Using intact chloroplasts isolated from Arabidopsis leaves and (15)N
      labelled nitrite we show that a light-dependent nitrite uptake into chloroplasts
      is increased in PII knock-out mutants when compared to the wild-type. This leads
      to a higher incorporation of (15)N into ammonium and amino acids in the mutant
      chloroplasts. However, the uptake differences do not depend on GS/GOGAT
      activities. Our observations suggest that PII is involved in the regulation of
      nitrite uptake into higher plant chloroplasts.

PMID- 18325337
TI  - Crystal structure of the Clostridium limosum C3 exoenzyme.
AB  - C3-like toxins ADP-ribosylate and inactivate Rho GTPases. Seven C3-like ADP
      ribosyltransferases produced by Clostridium botulinum, Clostridium limosum,
      Bacillus cereus and Staphylococcus aureus were identified and two representatives
      -C3bot from C. botulinum and C3stau2 from S. aureus--were crystallized. Here we
      present the 1.8A structure of C. limosum C3 transferase C3lim and compare it to
      the structures of other family members. In contrast to the structure of apo
      C3bot, the canonical ADP-ribosylating turn turn motif is observed in a primed
      conformation, ready for NAD binding. This suggests an impact on the binding mode
      of NAD and on the transferase reaction. The crystal structure explains why auto
      ADP-ribosylation of C3lim at Arg41 interferes with the ADP-ribosyltransferase
      activity of the toxin.

PMID- 18325338
TI  - Germ cell-specific gene 1 targets testis-specific poly(A) polymerase to the
      endoplasmic reticulum through protein-protein interactions.
AB  - Testis-specific poly(A) polymerase (TPAP) is a cytoplasmic poly(A) polymerase
      that is highly expressed in round spermatids. We identified germ cell-specific
      gene 1 (GSG1) as a TPAP interaction partner protein using yeast two-hybrid and
      coimmunoprecipitation assays. Subcellular fractionation analysis showed that GSG1
      is exclusively localized in the endoplasmic reticulum (ER) of mouse testis where
      TPAP is also present. In NIH3T3 cells cotransfected with TPAP and GSG1, both
      proteins colocalize in the ER. Moreover, expression of GSG1 stimulates TPAP
      targeting to the ER, suggesting that interactions between the two proteins lead
      to the redistribution of TPAP from the cytosol to the ER.

PMID- 18325339
TI  - Cell responses regulated by early reorganization of actin cytoskeleton.
AB  - Microfilaments exist in a dynamic equilibrium between monomeric and polymerized
      actin and the ratio of monomers to polymeric forms is influenced by a variety of
      extracellular stimuli. The polymerization, depolymerization and redistribution of
      actin filaments are modulated by several actin-binding proteins, which are
      regulated by upstream signalling molecules. Actin cytoskeleton is involved in
      diverse cellular functions including migration, ion channels activity, secretion,
      apoptosis and cell survival. In this review we have outlined the role of actin
      dynamics in representative cell functions induced by the early response to
      extracellular stimuli.

PMID- 18325340
TI  - Resonance Raman spectroscopy can detect structural changes in haemozoin (malaria
      pigment) following incubation with chloroquine in infected erythrocytes.
AB  - Resonance Raman spectroscopy was applied to monitor the effects of chloroquine
      (CQ) treatment on cultures of Plasmodium falciparum trophozoites. A number of
      bands assigned to A(1g) and B(1g) modes characteristic of the haemozoin aggregate
      are reduced in intensity in the CQ-treated cells, however, no bands from the CQ
      are observed. The intensity changes are attributed to intermolecular drug binding
      of the CQ in a sandwich type complex between ferriprotoporphyrin IX (FePPIX)
      dimer units. It is postulated that the CQ binds via pi-pi interactions between
      adjacent and orientated porphyrins thereby disrupting the haemozoin aggregate and
      reducing excitonic interactions between adjacent haems. The results show the
      potential of Raman microscopy as a screening tool for FePPIX:drug interactions in
      live cells.

PMID- 18325341
TI  - Overexpression of a TFIIIA-type zinc finger protein gene ZFP252 enhances drought
      and salt tolerance in rice (Oryza sativa L.).
AB  - We previously identified a salt and drought stress-responsive TFIIIA-type zinc
      finger protein gene ZFP252 from rice. Here we report the functional analysis of
      ZFP252 using gain- and loss-of-function strategies. We found that overexpression
      of ZFP252 in rice increased the amount of free proline and soluble sugars,
      elevated the expression of stress defense genes and enhanced rice tolerance to
      salt and drought stresses, as compared with ZFP252 antisense and non-transgenic
      plants. Our findings suggest that ZFP252 plays an important role in rice response
      to salt and drought stresses and is useful in engineering crop plants with
      enhanced tolerance to salt and drought stresses.

PMID- 18325342
TI  - Human fortilin is a molecular target of dihydroartemisinin.
AB  - Dehydroartemisinin (DHA) is an effective anti-malaria agent. Fortilin is an anti
      apoptotic molecule overexpressed in many human cancers. Here, we show that DHA
      binds human fortilin, increases the ubiquitination of fortilin, shortens
      fortilin's half-life in a proteasome-dependent fashion, and reduces cellular
      levels of fortilin in varieties of cells. DHA induced DNA fragmentation in U2OS
      cells in a fortilin-dependent manner. The fortilin-knocked-down cells were less
      susceptible--and fortilin-overexpressing cells more susceptible--to DHA than were
      wild-type cells, suggesting that apoptotic effects of DHA are-at least partly
      conferred through fortilin. Together, these data suggest that fortilin is a
      molecular target of DHA. DHA and its derivative may prove to be viable anti
      cancer agents in fortilin-overexpressing cancers.

PMID- 18325343
TI  - sll1961 is a novel regulator of phycobilisome degradation during nitrogen
      starvation in the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The sll1961 gene was reported to encode a regulatory factor of photosystem
      stoichiometry in the cyanobacterium Synechocystis sp. PCC 6803. We here show that
      the sll1961 gene is also essential for the phycobilisome degradation during
      nitrogen starvation. The defect in phycobilisome degradation was observed in the
      sll1961 mutant despite the increased expression of nblA, a gene involved in
      phycobilisome degradation during nitrogen starvation. Photosystem stoichiometry
      is not affected by nitrogen starvation in the sll1961 mutant nor in the wild
      type. The results indicate the presence of a novel pathway for phycobilisome
      degradation control independent of nblA expression.

PMID- 18325344
TI  - Interaction between fortilin and transforming growth factor-beta stimulated clone
      22 (TSC-22) prevents apoptosis via the destabilization of TSC-22.
AB  - Yeast two-hybrid screening was conducted using a human ovary cDNA library to
      search for a novel binding protein using transforming growth factor-beta
      stimulated clone-22 (TSC-22). The selected protein was fortilin, which has been
      characterized as a nuclear anti-apoptotic protein. Overexpression of fortilin in
      ovarian carcinoma cells reversed TSC-22-mediated apoptosis, and the inhibition of
      fortilin expression via small interfering RNA (siRNA) resulted in an increase in
      the apoptosis of ovarian carcinoma cells. Moreover, fortilin overexpression
      promoted the degradation of TSC-22. Thus, an interaction between fortilin and TSC
      22 prevents apoptosis via the destabilization of TSC-22 in ovarian carcinoma
      cells.

PMID- 18325345
TI  - Distinct heparin binding sites on VEGF165 and its receptors revealed by their
      interaction with a non sulfated glycoaminoglycan (NaPaC).
AB  - We previously demonstrated that a non sulfated analogue of heparin, phenylacetate
      carboxymethyl benzylamide dextran (NaPaC) inhibited angiogenesis. Here, we
      observed that NaPaC inhibited the VEGF165 binding to both VEGFR2 and NRP-1 and
      abolished VEGFR2 activity. Further, we explored the effects of NaPaC on VEGF165
      interactions with its receptors, VEGFR2 and NRP-1, co-receptor of VEGFR2. Surface
      plasmon resonance and affinity gel electrophoresis showed that NaPaC interacted
      directly with VEGF165, VEGFR2 and NRP-1 but not with heparin-independent factor
      such as VEGF121. NaPaC completely inhibited the heparin binding to VEGF165, NRP-1
      and VEGFR2. We found that NaPaC bound to all three molecules, VEGF165, VEGFR2 and
      NRP-1, but was more effective in inhibiting heparin binding to VEGF165. These
      results suggested that heparin binding sites of VEGFR2 and NRP-1 were different
      from those of VEGF165.

PMID- 18325346
TI  - Role and regulation of ferritin H in rotenone-mediated mitochondrial oxidative
      stress.
AB  - Tight regulation of intracellular iron levels in response to mitochondrial
      dysfunction is an important mechanism that prevents oxidative stress, thereby
      limiting cellular damage. Here, we describe a cytoprotective response involving
      transcriptional activation of the ferritin H gene in response to the
      mitochondrial complex I inhibitor and neurotoxic compound rotenone. Rotenone
      exposure increased ferritin H mRNA and protein synthesis in NIH3T3 fibroblasts
      and SH-SY5Y neuroblastoma cells. Transient transfection of a ferritin H promoter
      luciferase reporter into NIH3T3 cells showed that ferritin H was
      transcriptionally activated by rotenone through an antioxidant-responsive element
      (ARE). Chromatin immunoprecipitation assays showed that rotenone treatment
      enhanced binding of Nrf2 and JunD transcription factors to the ARE. In addition,
      rotenone induced production of reactive oxygen species (ROS), and pretreatment
      with N-acetylcysteine abrogated ferritin H mRNA induction by rotenone, suggesting
      that this response is oxidative stress-mediated. Furthermore, reduced ferritin H
      expression by siRNA sensitized cells to rotenone-induced apoptosis with increased
      ROS production and annexin V-positive cells. Taken together, these results
      suggest that ferritin H transcription is activated by rotenone via an oxidative
      stress-mediated pathway leading to ARE activation and may be critically important
      to protect cells from mitochondrial dysfunction and oxidative stress.

PMID- 18325347
TI  - Endothelial nitric oxide synthase gene haplotypes and circulating nitric oxide
      levels significantly associate with risk of essential hypertension.
AB  - Nitric oxide (NO), a potent vasodilator, plays a pivotal role in blood pressure
      regulation. Endothelial NO synthase gene (NOS3) polymorphisms influence NO
      levels. Here, we investigated the role of the -922A/G, -786T/C, 4b/4a, and 894G/T
      polymorphisms of the NOS3 and NO(x) levels in 800 consecutive unrelated subjects
      comprising 455 patients of essential hypertension and 345 controls. The
      polymorphisms were investigated independently and as haplotypes. Plasma NO(x)
      levels (nitrate and nitrite) were estimated by the Griess method. Genotype
      frequencies for the -786T/C, 4b/4a, and 894G/T polymorphisms differed
      significantly (P<0.001) between patients and controls and were associated with an
      increased risk of hypertension (OR=2.0, OR=3.8, OR=1.6, respectively). The 4
      locus haplotypes ATaG (H1), ATaT (H2), and GCaG (H3) were significantly
      associated with essential hypertension and served as susceptible haplotypes
      (P<or=0.0001). On the other hand, haplotypes ATbG (H4) and GTbG (H5) were
      negatively associated with hypertension and served as protective haplotypes
      (P<0.0001). NO(x) levels were significantly lower in patients than controls
      (P<0.0001). The individual polymorphisms showed marginal association with NO(x)
      level; however, the susceptible haplotype H2 associated significantly with lower
      NO(x) levels in patients (P<0.001) and conversely the haplotype H4 with higher
      NO(x) levels in controls (P<0.001). In conclusion, the 4b/4a and likely -786T/C
      polymorphisms were identified as the determinants modifying the risk of
      hypertension. This study identifies the NOS3 variants and haplotypes as genetic
      risk factors and as useful markers of increased susceptibility to the risk of
      essential hypertension.

PMID- 18325348
TI  - Role of TGF-beta1-independent changes in protein neosynthesis, p38alphaMAPK, and
      cdc42 in hydrogen peroxide-induced senescence-like morphogenesis.
AB  - The role of TGF-beta1 in hydrogen peroxide-induced senescence-like morphogenesis
      has been described. The aim of this work was to investigate whether TGF-beta1
      independent changes in protein synthesis are involved in this morphogenesis and
      to study possible mechanisms occurring earlier than TGF-beta1 overexpression.
      Among the multiple TGF-beta1-independent changes in protein neosynthesis,
      followed or not by posttranslational modifications, identified by proteomic
      analysis herein, those of ezrin, L-caldesmon, and HSP27 were particularly
      studied. Rho-GTPase cdc42 was shown to be responsible for p38(MAPK) activation,
      in turn triggering phosphorylation of L-caldesmon and HSP27. Cdc42 was also shown
      to be mainly responsible for the increase in TGF-beta1 mRNA level observed at 24
      h after treatment with H(2)O(2) and onward. This study further clarified the
      mechanisms of senescence-like morphogenesis in addition to the previously
      demonstrated role of TGF-beta1 signaling pathways.

PMID- 18325349
TI  - High glucose induction of DNA-binding activity of the transcription factor
      NFkappaB in patients with diabetic nephropathy.
AB  - The aim of this study was to investigate whether high glucose induces aldose
      reductase (AKR1B1) expression through NFkappaB, which may contribute to the
      pathogenesis of diabetic nephropathy. 34 Caucasoid patients with type 1 diabetes
      were recruited; 20 nephropaths and 14 long-term uncomplicated subjects.
      Peripheral blood mononuclear cells (PBMCs) were cultured under normal or high
      glucose (25 mmol/l of d-glucose) with or without an aldose reductase inhibitor
      (ARI). High glucose increased NFkappaB binding activities in the PBMCs from
      nephropaths compared to the uncomplicated subjects (1.77+/-0.22 vs. 1.16+/-0.04,
      p=0.02). ARI induced a substantially greater decrease of NFkappaB binding
      activities in the nephropaths compared to the uncomplicated subjects (0.58+/-0.06
      vs. 0.79+/-0.06, p=0.032). AKR1B1 protein levels in the nephropaths were
      increased under high glucose conditions and decreased in the presence of an ARI,
      whilst the silencing of the NFkappaB p65 gene in vitro reduced the
      transcriptional activities of AKR1B1 in luciferase assays. These results show
      that NFkappaB induces AKR1B1expression under high glucose conditions, and the
      pattern of expression differs between nephropaths and the uncomplicated subjects.

PMID- 18325350
TI  - Zinc mesoporphyrin induces rapid and marked degradation of the transcription
      factor Bach1 and up-regulates HO-1.
AB  - Heme oxygenase 1 (HO-1) is the first and rate-controlling enzyme in heme
      degradation. Bach1 is a mammalian transcriptional repressor of HO-1. To
      understand how zinc mesoporphyrin (ZnMP) induces the expression of HO-1, we
      investigated the effects of ZnMP on Bach1 mRNA and protein levels in human
      hepatoma Huh-7 cells by quantitative RT-PCR and Western blots. We found that ZnMP
      markedly up-regulated HO-1 mRNA and protein levels, and rapidly and significantly
      decreased Bach1 protein levels by increasing degradation of Bach1 protein [half
      life (t(1/2)) from 19 h to 45 min], whereas ZnMP did not influence Bach1 mRNA
      levels. The proteasome inhibitors, epoxomicin and MG132, significantly inhibited
      degradation of Bach1 by ZnMP in a dose-dependent fashion, indicating that the
      degradation of Bach1 by ZnMP is proteasome-dependent. Purified Bach1 C-terminal
      fragment bound heme, but there was no evidence for binding of ZnMP to the heme
      binding region of Bach1. In conclusion, ZnMP produces profound post
      transcriptional down-regulation of Bach1 protein levels and transcriptional up
      regulation of HO-1. Our results indicate that ZnMP up-regulates HO-1 gene
      expression by markedly increasing Bach1 protein degradation in a proteasome
      dependent manner.

PMID- 18325351
TI  - Coping with cryptic and defective transcripts in plant mitochondria.
AB  - Plant mitochondria are particularly prone to the production of both defective and
      cryptic transcripts as a result of the complex organisation and mode of
      expression of their genome. Cryptic transcripts are generated from intergenic
      regions due to a relaxed control of transcription. Certain intergenic regions are
      transcribed at higher rates than genuine genes and therefore, cryptic transcripts
      are abundantly produced in plant mitochondria. In addition, primary transcripts
      from genuine genes must go through complex post-transcriptional processes such as
      C to U editing and cis or trans splicing of group II introns. These post
      transcriptional processes are rather inefficient and as a result, defective
      transcripts are constantly produced in plant mitochondria. In this review, we
      will describe the nature of cryptic and defective transcripts as well as their
      fate in plant mitochondria. Although RNA surveillance is crucial to establishing
      the final transcriptome by degrading cryptic transcripts, plant mitochondria are
      able to tolerate a surprising high level of defective transcripts.

PMID- 18325352
TI  - Preface: The apical junctional complexes, composition, structure, and
      characteristics.

PMID- 18325353
TI  - Considerations when introducing a new cardiac MDCT service. Avoiding the
      pitfalls.
AB  - The widespread introduction of multidetector computed tomography (MDCT) into
      mainstream imaging departments has enabled many centres to undertake cardiac MDCT
      and, in particular, MDCT coronary angiography. This review highlights the areas
      that need consideration when introducing a new cardiac MDCT service and covers
      both technical and non-technical aspects. This includes equipment requirements,
      personnel, training, patient selection and preparation, cardiac CT protocols and
      post-processing techniques, and potential pitfalls.

PMID- 18325354
TI  - Cardiac radiology.
AB  - Cardiac imaging is a relatively new and developing field. This article is aimed
      at radiology trainees, radiographers, and non-specialist radiologists who would
      like to learn more about this exciting subspecialty. What follows is a list of
      carefully selected web resources that may also be of interest to specialists for
      use in training. Hyperlinks are available in the electronic version of this
      article.

PMID- 18325355
TI  - MRI of soft-tissue masses: the relationship between lesion size, depth, and
      diagnosis.
AB  - AIMS: To identify the relationship between depth and size of soft-tissue mass
      lesions relative to histological diagnosis in a range of malignant neoplastic,
      benign neoplastic, and non-neoplastic conditions on magnetic resonance imaging
      (MRI). METHOD: The MRI findings of 571 consecutive patients referred to a supra
      regional orthopaedic oncology unit with a suspected soft-tissue neoplasm were
      reviewed and included in the study. The patient age, histological diagnosis,
      lesion size, anatomical location, and lesion depth (superficial or deep to
      fascia) were recorded. RESULTS: There were 288 males and 283 females (mean age 48
      years, age range 2-92 years). The mean age was 54.1 years for malignant
      neoplastic lesions compared with 40.1 years for benign neoplastic and 45.4 years
      for non-neoplastic conditions. There was a significant age difference when
      malignant lesions were compared with benign neoplastic and non-neoplastic lesions
      (p<0.001). No significant relationship was present between lesion depth (480
      deep, 91 superficial) and diagnosis (288 malignant neoplastic, 197 benign
      neoplastic and 86 non-neoplastic lesions). However, a significant relationship
      was identified between lesion size and diagnosis (p<0.001). Furthermore, a
      significant relationship was identified when lesion size greater than 5 cm,
      lesion depth, and diagnosis were analysed. CONCLUSION: Current guidelines suggest
      the most important variables for assessing risk of malignancy in a soft-tissue
      lesion include size, depth in relation to the fascia, increasing size, and pain.
      The current study suggests that relationship to fascia is less important as a
      predictor of malignant potential in a patient cohort treated at a supra-regional
      centre. Significant risk factors include increasing patient age and lesion size
      greater than or equal to 5 cm.

PMID- 18325357
TI  - Increased diagnosis of pulmonary embolism without a corresponding decline in
      mortality during the CT era.
AB  - AIM: To determine the association between the increasing computed tomography (CT)
      use for suspected pulmonary embolism (PE) on the annual rates of PE diagnosis and
      mortality, using time as a surrogate for CT use. MATERIALS AND METHODS: New York
      State's (NYS) Statewide Planning and Research Cooperative System (SPARCS)
      database was used to determine the rate of PE diagnosis and mortality between 1
      January 1994 and 31 December 2004. Risk factors for PE were investigated.
      Bivariate and multivariate analyses were performed to determine the relationships
      between variables. RESULTS: The study population consisted of 24,871,131 NYS
      patients. The number of patients with a primary diagnosis of PE nearly doubled
      over the study period, from 2590 in 1994 to 4920 in 2004, while total admissions
      remained stable. PE deaths did not vary significantly over time, from 157 in 1994
      to 159 in 2004 and did not vary with the diagnoses of PE. Age-adjusted
      multivariate analysis did not reveal a significant association between the rates
      of PE diagnosis or mortality and corresponding risk factors. CONCLUSION: This
      study suggests that the increased use of CT in patients with suspected PE has led
      to an increase in the diagnosis of PE without a corresponding decline in
      mortality. Further evidence, using data on individual patients, is needed to
      determine the appropriate role of CT in evaluating patients with suspected PE.

PMID- 18325358
TI  - The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in
      patients with prostate cancer: a meta-analysis.
AB  - AIM: To compare the diagnostic accuracy of computed tomography (CT) and magnetic
      resonance imaging (MRI) in the diagnosis of lymph node metastases in prostate
      cancer. METHODS: After a comprehensive literature search, studies were included
      that allowed construction of contingency tables for detection of lymph node
      metastases using CT or MRI. In addition, a summary receiver-operating
      characteristic (ROC) analysis was performed. RESULTS: A total of 24 studies were
      included. For CT, pooled sensitivity was 0.42 (0.26-0.56 95% CI) and pooled
      specificity was 0.82 (0.8-0.83 95% CI). For MRI, the pooled sensitivity was 0.39
      (0.22-0.56 95% CI) and pooled specificity was 0.82 (0.79-0.83 95% CI). The
      differences in performance of CT and MRI were not statistically significant.
      CONCLUSION: CT and MRI demonstrate an equally poor performance in the detection
      of lymph node metastases from prostate cancer. Reliance on either CT or MRI will
      misrepresent the patient's true status regarding nodal metastases, and thus
      misdirect the therapeutic strategies offered to the patient.

PMID- 18325359
TI  - Experience with ultrasonographically guided vacuum-assisted resection of benign
      breast tumors.
AB  - AIM: To evaluate the feasibility and safety of vacuum-assisted resection of
      benign breast tumours using an 8 G handheld device. MATERIALS AND METHODS: Over a
      2-year period, 22 patients with 26 breast tumours diagnosed as benign using
      aspiration biopsy cytology were enrolled. The mean patient age was 38 years, and
      the mean maximal diameter of the tumour was 13 mm. A handheld Aloka SSD 6500
      ultrasonography device with a linear-type 7.5 MHz transducer was inserted into
      the posterior aspect of the tumour with the patient under local anaesthesia, and
      the tumour was resected under ultrasonographic guidance. RESULTS: This method was
      employed successfully in all patients, and the mean operation time was 33 min.
      Post-procedure complications included subcutaneous bleeding in 12 cases and
      haematoma in one. The pathological diagnoses were fibroadenoma in 16 cases,
      mastopathy in six, and tubular adenoma and pseudoangiomatous stromal hyperplasia
      in two cases each, respectively. Follow-up ultrasonography revealed residual
      tumours in four cases (15.4%). CONCLUSIONS: Although this method is feasible and
      safe without severe complications, it is necessary to select appropriate
      patients, and to obtain informed consent regarding the possibility of recurrence
      or residual tumour.

PMID- 18325360
TI  - Secretin-assisted CT of the pancreas: improved pancreatic enhancement and tumour
      conspicuity.
AB  - PURPOSE: The primary aim of this prospective pilot study was to determine if the
      administration of intravenous secretin prior to contrast-enhanced computed
      tomography (CT) improves pancreatic enhancement and pancreatic tumor conspicuity.
      The second aim was to determine the optimal timing for secretin administration
      prior to contrast-enhanced CT. METHODS: Local ethics committee approval was
      obtained. 35 patients (18 men, 17 women; mean age, 67.6 years; age range; 25 to
      86 years) with known or suspected pancreatic malignancy or an abdominal
      malignancy underwent a helical CT of the pancreas. The pancreas was first
      localised on an unenhanced scan using 10mm sections. Following 120 ml of
      intravenous 300 mg/ml of non ionic contrast medium (CM), injected at a rate of 5
      ml/s, images of the pancreas (3mm slice thickness) and liver (8mm slice
      thickness) were obtained at 40 and 70 seconds respectively. A second CT was
      obtained 1-5 days after the first one using the same CT and intravenous contrast
      medium injection parameters. However 100 IU of secretin was given as an
      intravenous bolus between 0 and 5 min prior to intravenous contrast medium
      administration. Each patient acted as their own control. The attenuation in
      Hounsfield Units (HU) was recorded on non-contrast, pancreatic phase and portal
      venous phases for both secretin and non-secretin CTs, in the pancreas and
      pancreatic tumors (where present). Tumor conspicuity was calculated (in the 19
      patients with pancreatic adenocarcinomas) by subtracting pancreatic tumor
      attenuation from pancreatic attenuation. Statistical evaluation comparing pre and
      post secretin enhancement was performed using matched paired t-tests. RESULTS: A
      significant increase in pancreatic enhancement was observed when secretin was
      injected at 2 to 3 min before contrast material injection (the increase in
      pancreatic density following secretin at 2 min was 31.5+/-10 HU (29.2%) (p=.035);
      and at 3 min was 23.2+/-7.8 HU (22.7%) (p=.041). Pancreatic tumor conspicuity in
      the pancreatic phase was most marked when secretin was injected between 2 to 4
      min before contrast medium, with 4 min showing a statistically significant
      increase in tumor conspicuity, 48.2+/-14.2 HU (p=.04). CONCLUSION: Imaging in the
      pancreatic phase 2 to 4 min after administration of intravenous secretin leads to
      greater enhancement of the pancreas with greater tumor conspicuity, than imaging
      without secretin.

PMID- 18325361
TI  - An 8-year review of barium studies in the diagnosis of gastroparesis.
AB  - AIM: To determine the utility of barium studies for diagnosing gastroparesis in
      patients with nausea, vomiting, or other related symptoms. MATERIALS AND METHODS:
      Radiology files revealed gastroparesis without gastric outlet obstruction on
      upper gastrointestinal tract barium studies in 50 patients with nausea, vomiting,
      and other related symptoms. Original reports and images were reviewed to
      determine whether gastric peristalsis was decreased/absent and to investigate
      gastric dilatation, fluid or debris, and delayed emptying of barium. Twenty
      patients (40%) had nuclear gastric emptying studies. Medical records were
      reviewed to determine the presentation, treatment, and course. The diagnosis of
      gastroparesis was considered accurate if patients with gastroparesis on barium
      studies responded to treatment. RESULTS: Forty-six patients (92%) had
      predisposing factors for gastroparesis, including narcotics and diabetes. Forty
      five patients (90%) presented with nausea or vomiting, and 40 patients (80%) had
      one or more other symptoms, including bloating, early satiety, postprandial
      fullness, and abdominal pain. Barium studies revealed decreased gastric
      peristalsis in 46 (92%) of the 50 patients and absent peristalsis in four (8%);
      46 patients (92%) had additional findings, including gastric dilatation in 30
      (60%), delayed emptying of barium in 27 (54%), debris in 28 (56%; bezoars in
      three), and retained fluid in 13 (26%). Thirteen (65%) of 20 patients with
      nuclear gastric emptying studies had delayed emptying of solids and seven (35%)
      had normal emptying. Thirty-five (83%) of 42 patients treated for gastroparesis
      had symptomatic improvement versus two (25%) of eight patients not treated.
      CONCLUSION: Patients with nausea, vomiting, or other related symptoms who have
      gastroparesis without gastric outlet obstruction on barium studies can be treated
      for this condition on the basis of the clinical and radiographic findings.

PMID- 18325362
TI  - Impaired left ventricular function has a detrimental effect on image quality in
      multi-detector row CT coronary angiography.
AB  - AIM: To determine whether there is a relationship between left ventricular (LV)
      haemodynamic parameters, circulation times, and arterial contrast opacification
      that might affect the image quality of computed tomography (CT) coronary
      angiography. METHODS: Thirty-six patients were included in the study: 18 with
      cardiomyopathy (CM) and LV dilatation of suspected ischaemic aetiology [age
      57.9+/-13.7 years, range 30-77 years; 14 male, four female; body mass index
      (BMI)=27.7+/-4.5, range 25.5-31.8] and 18 controls (age 62.3+/-9.4 years, range
      47-89 years; 10 male, eight female; BMI 27.8+/-6.6; range 19.2-33.6). Coronary
      artery image quality was assessed using a three-point visual scale; contrast
      medium circulation times, aortic root contrast attenuation, and LV functional
      parameters were studied. RESULTS: Visually reduced contrast opacification
      impaired image quality more often in the CM group than the control group (27.4
      versus 5.1%). A total of 55.6% CM patients had a contrast transit time ranging
      from 30-75 s; the number of "unassessable" segments increased with increasing
      transit time conforming to a fitted quadratic model (R2=0.74). The relationship
      between LV ejection fraction and contrast attenuation may also conform to a
      quadratic model (R2=0.71). CONCLUSION: LV haemodynamics influence coronary artery
      opacification using cardiac CT, and users imaging this subgroup must do so with
      the knowledge of this potential pitfall. The results indicate the need for
      further studies examining CT protocols in this clinical subgroup.

PMID- 18325363
TI  - Minimal-preparation abdomino-pelvic CT in frail and elderly patients: prognostic
      value of colonic and extracolonic findings.
AB  - AIM: To examine the overall survival of patients who had had been referred for
      minimal preparation abdomino-pelvic computed tomography (MPCT), and to assess the
      prognostic value of the colonic and extracolonic findings detected. METHODS AND
      MATERIALS: The survival of a cohort of 1029 elderly and frail patients, with
      clinical symptoms and signs suspicious for colorectal cancer (CRC), who had
      undergone MPCT between 1995 and 1998 was investigated. Univariate and
      multivariate survival analyses were undertaken according to the presence of CRC
      and extracolonic abnormalities (ECA). RESULTS: The median age of the 1029
      patients was 79.4 years. The overall median survival following MPCT was 5.4
      years; and 6.6 years if no abnormality was detected. On multivariate analysis,
      age, sex, CRC status, and number of ECAs were significant factors in overall
      survival. Median survival for those with confirmed CRC [n=91 (prevalence, 8.8%)]
      was 1.1 years, compared with 5.9 years without CRC (p<0.0001); and 2.4 years for
      those with one or more ECA [n=245 (prevalence, 23.8%)], compared with 6.1 years
      without ECA (p<0.0001). Survival was progressively shorter for increasing numbers
      of ECAs; and shorter for previously unknown non-CRC malignancies (n=24) compared
      with CRC (p<0.0001). CONCLUSIONS: MPCT appears to have prognostic potential in
      this patient population, with significant reductions in survival if a CRC or ECA
      is detected. The detection of ECA would appear to have at least as important an
      impact on the usefulness of the examination as the detection of CRC.

PMID- 18325364
TI  - Focal inflammation in the embryological ventral pancreas: assessment using CT and
      MRI.
AB  - AIM: To identify the characteristic computed tomography (CT) and magnetic
      resonance imaging (MRI) findings of nonuniform inflammation between the posterior
      aspect of the head and the remainder of the pancreas. MATERIALS AND METHODS: Two
      radiologists retrospectively evaluated images of 19 patients in whom the degree
      of attenuation in the CT images and/or the signal intensity in the MRI images
      differed between the posterior aspect of the head (ventral primordium) and the
      remainder of the pancreas (dorsal primordium) due to benign disorders other than
      uneven fatty replacement. Multiphase, contrast-enhanced CT examinations were
      performed in 17 patients. In five, T1- and T2-weighted images with and without
      fat suppression were obtained using a 1.5 T superconducting MRI system. RESULTS:
      The lesions were localized in the posterior aspect of the head in 17 patients. In
      two patients, the lesions occupied the posterior aspect of the head and extended
      to the neck. The lesions exhibited the following findings: inhomogeneous
      hypoattenuation (with spotty areas of relatively well-maintained contrast
      enhancement) during the pancreatic phase (17/17) and no intense peripheral
      enhancement or central necrotic areas (17/17) in CT images, hypointensity in T1
      weighed images (5/5), hyperintensity in T2-weighed images (4/5), no vascular
      invasion (19/19), failure to depict the entire course of Wirsung's duct (17/19),
      and calcification (13/19). Santorini's ducts were depicted in all but three
      patients. CONCLUSION: Focal inflammation in the embryological ventral pancreas
      exhibits a unique anatomical distribution and characteristic findings.

PMID- 18325365
TI  - MRI in the assessment of congenital vaginal anomalies.
AB  - AIM: To assess accuracy of magnetic resonance imaging (MRI) for the delineation
      of morphological abnormalities of the vagina in patients with congenital
      anomalies of the genito-urinary tract. MATERIALS AND METHODS: Fifty-one patients
      (median age 19 years; range 12-40 years) were studied. All were consecutively
      referred for MRI to assess genital tract anatomy, between 1996 and 2004, from a
      clinic specializing in congenital abnormalities of the urogenital tract. All
      patients were assessed clinically and underwent MRI. Images were reviewed
      retrospectively by an experienced radiologist. Where there was discordance
      between clinical and radiological findings a consensus diagnosis was achieved by
      the gynaecologists and radiologists reviewing all of the clinical and
      radiological evidence together, including assessment of vaginal length. RESULTS:
      The clinical data were incomplete for five women and the images non-diagnostic in
      two cases; consequently, 44 of 51 women had complete datasets and could be
      evaluated. Vaginas were abnormal in 30 of the 44 patients. There was discordance
      between the clinical and imaging findings at the initial review in three of the
      44 cases (6.8%). After consensus review, and with the inclusion of measurement of
      the vaginal length on MRI, the MRI and clinical findings were concordant in all
      cases. The initial discordance was due to two vaginal dimples not being
      appreciated on MRI and one case in which presence of vaginal tissue proximal to a
      mid-segment obstruction was not appreciated clinically. CONCLUSION: MRI is an
      accurate method of imaging vaginal anomalies. However, to achieve reliable
      results the radiologist requires details of previous surgery and the vaginal
      length must be measured.

PMID- 18325366
TI  - Low radiation dose CT technique for guidance of radiofrequency ablation of
      osteoid osteoma.

PMID- 18325367
TI  - Nuclear medicine in the assessment of differentiated thyroid cancer.
AB  - Despite modern multi-modality treatment, 10-30% of patients treated for
      differentiated thyroid cancer (DTC) ultimately develop local recurrence or
      metastatic disease. These malignancies are frequently slow-growing and secondary
      surgical resection is often undertaken along with radioactive iodine treatment.
      Correlation of radiological imaging with nuclear medicine studies is essential
      for individualized treatment planning, and to optimize this management.
      Radiologists should be familiar with the interpretation of various nuclear
      medicine studies used to image differentiated thyroid neoplasms.

PMID- 18325368
TI  - Cardiomyopathy: appearances on ECG-gated 64-detector row computed tomography.
AB  - Multi-detector row cardiac computed tomography (MDCT) with its high spatial and
      temporal resolution now has an established clinical role in cardiac imaging. The
      present review illustrates the MDCT appearances of cardiomyopathy, with reference
      to the normal myocardium, using multi-planar, near-isotropic imaging, three
      dimensional volume rendering, and ECG-gated multi-phasic functional imaging
      software capabilities of 64-MDCT. MRI and echocardiographic correlations are also
      provided where appropriate.

PMID- 18325369
TI  - An [123 I]MIBG-positive malignant lymphoma involving the adrenal gland with
      hypercatecholaminaemia.

PMID- 18325370
TI  - Bilateral osteochondrosis of the superior pole of the patellae in association
      with bilateral osteochondritis dissecans of the lateral femoral condyle.

PMID- 18325371
TI  - Spinal needle improves adequate thyroid nodule cytology.

PMID- 18325372
TI  - Re: Late presentation of developmental dysplasia of the hip following normal
      ultrasound examination.

PMID- 18325374
TI  - Electronic clinical challenges and images in GI. Biliocutaneous fistula secondary
      to pancreatic cancer.

PMID- 18325375
TI  - Electronic clinical challenges and images in GI. Abdominal tuberculosis.

PMID- 18325377
TI  - FDA approves first quick test for drug-resistant Staphylococcus infections.

PMID- 18325380
TI  - Americans rate health care a top issue for candidates to discuss.

PMID- 18325381
TI  - Medical education: a key partner in realizing personalized medicine in
      gastroenterology.

PMID- 18325382
TI  - Genetic association studies: from "searching under the lamppost" to "fishing in
      the pond".

PMID- 18325383
TI  - Implantable gastric electrical stimulation: ready for prime time?

PMID- 18325384
TI  - Clinical challenges and images in GI. Aortitis as a rare complication of Crohn's
      disease.

PMID- 18325385
TI  - Clinical challenges and images in GI. Esophageal tubular duplication.

PMID- 18325386
TI  - Rosiglitazone for active ulcerative colitis: a randomized placebo-controlled
      trial.
AB  - BACKGROUND & AIMS: Thiazolidinedione ligands for the gamma subtype of peroxisome
      proliferator-activated receptors (PPARgamma), widely used to treat type 2
      diabetes mellitus, have been proposed as novel therapies for ulcerative colitis
      (UC). METHODS: This multicenter, randomized, double-blind, placebo-controlled
      clinical trial compared the efficacy of rosiglitazone (Avandia; GlaxoSmithKline,
      Philadelphia, PA) 4 mg orally twice daily vs placebo twice daily for 12 weeks in
      105 patients with mild to moderately active UC. Disease activity was measured
      with the Mayo score. The primary end point was clinical response (>/=2-point
      reduction) at week 12. Clinical remission (Mayo score </=2), endoscopic
      remission, and quality of life were secondary outcomes. RESULTS: After 12 weeks
      of therapy, 23 patients (44%) treated with rosiglitazone and 12 patients (23%)
      treated with placebo achieved clinical response (P = .04). Remission was achieved
      in 9 patients (17%) treated with rosiglitazone and 1 patient (2%) treated with
      placebo (P = .01). Endoscopic remission was uncommon in either treatment arm (8%
      rosiglitazone vs 2% placebo; P = .34). Clinical improvement was evident as early
      as 4 weeks after beginning treatment (P = .049). Quality of life was improved
      significantly at week 8 (P = .01), but not at week 4 (P = .48) or week 12 (P =
      .14). Serious adverse events were rare. CONCLUSIONS: Rosiglitazone was
      efficacious in the treatment of mild to moderately active UC.

PMID- 18325387
TI  - Regulatory polymorphisms in the promoter of CXCL10 gene and disease progression
      in male hepatitis B virus carriers.
AB  - BACKGROUND & AIMS: The importance of expression of interferon gamma-inducible
      protein of 10 kilodaltons (IP-10, CXCL10) during chronic hepatitis B virus (HBV)
      infection has been recently emphasized. In this report, we investigated whether
      the naturally occurred sequence variations in the CXCL10 gene impact liver damage
      and disease progression of chronic HBV infection. METHODS: A hospital-based case
      control study was conducted, and a total of 613 and 1787 unrelated Han Chinese
      HBV carriers were recruited from Beijing and Chongqing, respectively. We
      systematically screened sequence variations in the CXCL10 gene and examined the
      association between the variations in this gene and susceptibility to disease
      progression of chronic HBV infection in Chinese populations from Beijing and
      Chongqing. Functional analyses were conducted to verify the biological
      significances of the associated genetic variation. RESULTS: We identified that
      the polymorphism G-201A, located in the promoter region of CXCL10, was associated
      with susceptibility to disease progression in male HBV carriers (dominant model;
      odds ratio, 1.53; P = .001). Functional analyses show that the G-201A
      polymorphism alters the binding affinity of nuclear protein and regulates CXCL10
      expression. We observed higher CXCL10 transcription in interferon gamma
      stimulated peripheral blood mononuclear cells with the disease-susceptible
      genotypes. Enzyme-linked immunosorbent assay and immunohistochemical analysis
      showed augmented CXCL10 production in serum and liver tissues of progressed HBV
      carriers. CONCLUSIONS: The novel regulatory polymorphism G-201A [corrected] in
      the promoter of CXCL10 gene could be a part of the genetic variation underlying
      the susceptibility of individuals to disease progression of chronic HBV
      infection.

PMID- 18325388
TI  - Substance P as a novel anti-obesity target.
AB  - BACKGROUND & AIMS: Substance P (SP) is an 11-amino acid peptide that belongs to
      the tachykinin family of peptides. SP acts in the brain and in the periphery as a
      neuropeptide, neurotransmitter, and hormone affecting diverse physiologic
      pathways, mainly via its high-affinity neurokinin-1 receptor (NK-1R). Its
      presence in the hypothalamus and other areas of the brain that regulate feeding
      as well as in the stomach and small intestine prompted us to investigate its role
      on appetite control and energy balance. METHODS: CJ 012,255 (CJ), a SP antagonist
      that binds to NK-1R, was injected into lean, diet-induced obese (DIO), and
      genetically obese (ob/ob) mice, and its effects on body weight, adiposity, and
      insulin sensitivity were investigated. RESULTS: CJ administration prevented
      weight gain and accumulation of fat after 2 weeks of high-fat feeding, whereas
      similar CJ treatment in obese mice (following 3 months of high-fat diet) resulted
      in weight loss, reduction in adiposity, and improvement of insulin sensitivity,
      in part because of inhibition of food intake. The effects of SP in the control of
      energy balance are, at least in part, leptin independent because CJ treatment was
      also effective in leptin-deficient mice. Peripheral SP administration resulted in
      a mild, dose-dependent increase in food intake, evident 3 hours post-SP
      injection. CONCLUSIONS: CJ reduces appetite and promotes weight loss in mice. We
      speculate that NK-1R antagonists, already tested in clinical trials for various
      diseases, may represent a potential target against obesity.

PMID- 18325389
TI  - Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their
      siderophores.
AB  - BACKGROUND & AIMS: Hypoxia inducible factor-1 (HIF-1) is the key transcriptional
      regulator during adaptation to hypoxia. Recent studies provide evidence for HIF-1
      activation during bacterial infections. However, molecular details of how
      bacteria activate HIF-1 remain unclear. Here, we pursued the role of bacterial
      siderophores in HIF-1 activation during infection with Enterobacteriaceae.
      METHODS: In vivo, HIF-1 activation and HIF-1-dependent gene induction in Peyer's
      patches were analyzed after orogastric infection with Yersinia enterocolitica.
      The course of an orogastric Y enterocolitica infection was determined using mice
      with a deletion of HIF-1alpha in the intestine. In vitro, the mechanism of HIF-1
      activation was analyzed in infections with Y enterocolitica, Salmonella enterica
      subsp enterica, and Enterobacter aerogenes. RESULTS: Infection of mice with Y
      enterocolitica led to functional activation of HIF-1 in Peyer's patches. Because
      mice with deletion of HIF-1alpha in the intestinal epithelium showed a
      significantly higher susceptibility to orogastric Y enterocolitica infections,
      bacterial HIF-1 activation appears to represent a host defense mechanism.
      Additional studies with Y enterocolitica, S enterica subsp enterica, or E
      aerogenes, and, moreover, application of their siderophores (yersiniabactin,
      salmochelin, aerobactin) caused a robust, dose-dependent HIF-1 response in human
      epithelia and endothelia, independent of cellular hypoxia. HIF-1 activation
      occurs most likely because of inhibition of prolylhydroxylase activity and is
      abolished upon infection with siderophore uptake deficient bacteria. CONCLUSIONS:
      Taken together, this study reveals what we believe to be a previously
      unrecognized role of bacterial siderophores for hypoxia-independent activation of
      HIF-1 during infection with human pathogenic bacteria.

PMID- 18325390
TI  - Chronic enteric salmonella infection in mice leads to severe and persistent
      intestinal fibrosis.
AB  - BACKGROUND & AIMS: Intestinal fibrosis and stricture formation are serious
      complications of Crohn's disease, often requiring surgical intervention.
      Unfortunately, the mechanisms underlying intestinal fibrosis development are
      poorly understood, in part because of the lack of relevant animal models. Here,
      we present a novel murine model of severe and persistent intestinal fibrosis
      caused by chronic bacterial-induced colitis. METHODS: Mice were treated with
      streptomycin 24 hours prior to oral infection with Salmonella enterica serovar
      Typhimurium. Tissues were analyzed for bacterial colonization and inflammation,
      and fibrosis was assessed by Masson's trichrome staining and collagen
      quantification. Expression of the profibrotic cytokines transforming growth
      factor-beta1, connective tissue growth factor and insulin-like growth factor-I
      was determined, and the cell types present in fibrotic tissues were assessed by
      immunohistochemistry. RESULTS: Infection led to chronic Salmonella colonization
      of the cecum and colon followed by edema, mucosal ulcerations, and severe
      transmural inflammation. This pathology was accompanied by significantly elevated
      expression of transforming growth factor-beta1, connective tissue growth factor,
      and insulin-like growth factor-I along with extensive type I collagen deposition
      in the cecal mucosa, submucosa, and muscularis mucosa of infected mice. Fibrosis
      was evident by 7 days postinfection, peaking at day 21 and still present at day
      70. The fibrotic regions were found to be rich in fibroblasts and myofibroblasts.
      CONCLUSIONS: These data demonstrate that chronic Salmonella infection of the
      murine gastrointestinal tract leads to severe tissue fibrosis. Because this model
      is highly reproducible and easy to perform, it provides great potential for
      investigating both host and bacterial contributions to intestinal fibrosis.

PMID- 18325391
TI  - Continuous cell injury promotes hepatic tumorigenesis in cdc42-deficient mouse
      liver.
AB  - BACKGROUND & AIMS: The Rho small guanosine triphosphatase Cdc42 is critical for
      diverse cellular functions, including regulation of actin organization, cell
      polarity, intracellular membrane trafficking, transcription, cell-cycle
      progression, and cell transformation. This implies that Cdc42 might be required
      for liver function. METHODS: Mice in which Cdc42 was ablated in hepatocytes and
      bile duct cells were generated by Cre-loxP technology. Livers were examined by
      histologic, immunohistochemical, ultrastructural, and serum analysis to define
      the effect of loss of Cdc42 on liver structure. RESULTS: Mice lacking Cdc42 in
      their hepatocytes were born at Mendelian ratios. They did not show increased
      mortality but showed chronic jaundice. They developed hepatomegaly soon after
      birth, and signs of liver transformation, such as formation of nodules and
      tumors, became visible macroscopically at age 6 months. Hepatocellular carcinoma
      was observed 8 months after birth. Tumors grew slowly and lacked expression of
      nuclear beta-catenin. Lung metastases were observed at the late stage of
      carcinogenesis. Immunofluorescent examination and electron microscopy revealed
      severe defects in the liver. At the age of 2 months, the canaliculi between
      hepatocytes were greatly enlarged, although the tight junctions flanking the
      canaliculi appeared normal. Regular liver plates were absent. E-cadherin
      expression pattern and gap junction localization were distorted. Analysis of
      serum samples indicated cholestasis. CONCLUSIONS: We describe a mouse model in
      which chronic liver disease leads to hepatocarcinogenesis.

PMID- 18325392
TI  - Epigenetic inhibition of nuclear receptor small heterodimer partner is associated
      with and regulates hepatocellular carcinoma growth.
AB  - BACKGROUND & AIMS: Aberrant hypermethylation of promoter regions in cytosine
      guanine dinucleotides (CpG) islands has been shown to be associated with
      transcriptional silencing of tumor-suppressor genes in many cancers. This study
      evaluated the methylation profile and the tumor-suppressive function of the small
      heterodimer partner (SHP, NR0B2) in the development of human hepatocellular
      carcinoma (HCC). METHODS: Human HCC pathologic specimens and cell lines were used
      as model systems in this study. RESULTS: The expression of SHP is diminished in
      HCC pathologic specimens and cell lines by epigenetic silencing owing to SHP
      promoter hypermethylation. In vitro methylation decreased SHP promoter
      transactivation and nuclear receptor LRH-1 binding, an event that was reversed by
      demethylation. Overexpression of SHP inhibited HCC foci formation, arrested HCC
      tumor growth in xenografted nude mice, and increased the sensitivity of HCC cells
      to apoptotic stimuli. Further analysis of a total of 19 normal liver and 57 HCC
      specimens showed that down-regulation of SHP gene expression may be a common
      denominator of HCC. CONCLUSIONS: We propose that SHP functions as a novel tumor
      suppressor in the development of HCC. These findings provide new insight into the
      molecular mechanisms leading to this common cancer and may have both diagnostic
      and therapeutic applications.

PMID- 18325393
TI  - HIV increases HCV replication in a TGF-beta1-dependent manner.
AB  - BACKGROUND & AIMS: Human immunodeficiency virus (HIV) coinfection increases
      hepatitis C virus (HCV)-related progression of hepatic fibrosis, increases HCV
      persistence, and decreases response rates to interferon-based anti-HCV therapy.
      It has remained unclear how HIV, a nonhepatotropic virus, accelerates the
      progression of liver disease by HCV. METHODS: We explored the possibility that
      circulating HIV and/or its proteins contribute to the pathogenesis of HCV through
      engagement of extracellular coreceptors on hepatocytes. RESULTS: In this study,
      we found that inactivated HIV or gp120 increases HCV replication and enhances HCV
      regulated transforming growth factor (TGF)-beta1 expression in both a replicon
      and an infectious model of HCV. This proviral effect of HIV and gp120 on HCV
      replication is neutralized by antibodies to CCR5 or CXCR4. However, HIV and gp120
      did not alter type I interferon-mediated signaling in these HCV models,
      indicating that HIV regulates HCV replication through an alternative mechanism.
      Interestingly, we found that human TGF-beta1 also enhanced HCV replication. The
      effect of HIV on HCV replication was blocked by a neutralizing antibody to TGF
      beta1, indicating that its effects on HCV replication are TGF-beta1 dependent.
      CONCLUSIONS: These results suggest a novel mechanism by which HIV not only
      enhances HCV replication but also contributes to progression of hepatic fibrosis.

PMID- 18325394
TI  - Current view: intestinal stem cells and signaling.
AB  - Studies using mice have yielded significant amounts of information regarding
      signaling pathways, such as Wnt, bone morphogenic protein, PtdIns(3,4,5) kinase,
      and Notch, involved in intestinal development and homeostasis, including stem
      cell regulation and lineage specification and maturation. However, attempts to
      model signals definitively that control intestinal stem cells have been difficult
      because of a long-standing and recently reenergized debate surrounding their
      location. Although crypt-based columnar cells have been recently shown to display
      self-renewal and multipotential capacity, a large body of evidence supports long
      term label-retaining cells, located on average at the +4 position just above the
      Paneth cells, as putative stem cells. Herein, we propose that both these cell
      types represent true intestinal stem cells maintained in different states
      (quiescent vs actively cycling), presumably via interactions with different
      microenvironments. Finally, we review current findings regarding the roles of
      Wnt, bone morphogenic protein, PtdIns(3,4,5) kinase, and Notch pathways within
      the intestine.

PMID- 18325395
TI  - Hunting for celiac disease genes.

PMID- 18325396
TI  - Rho GTPase and Wnt signaling pathways in hepatocarcinogenesis.

PMID- 18325397
TI  - To be or not to be: generation of hepatocytes from cells outside the liver.

PMID- 18325399
TI  - Gluten-free diets in celiac disease: does life mean life?

PMID- 18325398
TI  - GERD and obesity: a real BIG issue!

PMID- 18325401
TI  - Farm animals and inflammatory bowel disease: old MacDonald had poor hygiene.

PMID- 18325403
TI  - Molecular information defines a new entity of hereditary colorectal cancer.

PMID- 18325406
TI  - The Peruvian contribution to the knowledge of the role of Helicobacter pylori
      infection in the genesis of gastric premalignant lesions that predispose to
      gastric cancer.

PMID- 18325407
TI  - Biliary injury after laparoscopic cholecystectomy: why still a problem?

PMID- 18325408
TI  - Assessing the risk of epstein-barr virus-related lymphoproliferative disorders
      before administration of visilizumab.

PMID- 18325409
TI  - Obesity and colorectal cancer risk.

PMID- 18325410
TI  - Predictability of clinical assessments for driving performance.
AB  - PROBLEM: As the number of older drivers grows, it is increasingly important to
      accurately identify at-risk drivers. This study tested clinical assessments
      predictive of real-time driving performance. METHOD: Selected assessment tools
      considered important in the identification of at-risk older drivers represented
      the domains of vision, cognition, motor performance, and driving knowledge.
      Participants were administered the battery of assessments followed by an on-road
      test. A univariate analysis was conducted to identify significant factors (<.05)
      to be included in a multivariate regression model. RESULTS: Assessments
      identified as independently associated with driving performance in the regression
      model included: FACTTM Contrast sensitivity slide-B, Rapid Pace Walk, UFOV
      rating, and MMSE total score. DISCUSSION: The domains of vision, cognitive, and
      motor performance were represented in the predictive model. SUMMARY: Due to the
      dynamic nature of the driving task, it is not likely that a single assessment
      tool will identify at risk drivers. IMPACT ON INDUSTRY: By standardizing the
      selection of clinical assessments used in driving evaluations, practitioners
      should be able to provide services more efficiently, more objectively, and more
      accurately to identify at-risk drivers.

PMID- 18325411
TI  - Work-related fatal injuries in parking lots, 1993-2002.
AB  - PROBLEM: Although parking facilities are a common feature of the landscape in the
      United States, little is known about their safety. METHOD: A dataset of parking
      lot fatalities for 1993-2002, created from the Census of Fatal Occupational
      Injury (CFOI) research file, was analyzed. RESULTS: The most common events in
      parking lots were contact with objects (15%), pedestrian fatalities (13%),
      homicides (36%), and suicides (11%). The perpetrators of parking lot fatalities,
      compared to all workplace homicides, were more likely to be known to the victim.
      CONCLUSION: The 206 work-related fatalities per year in parking lots present
      challenges to the safety community. Although much of the risk results from the
      usage of motor vehicles, violent acts are even more prominent. IMPACT ON
      INDUSTRY: Because homicides are most prevalent in parking lots, both
      administrative and environmental measures may lower the risk of homicide.
      Although difficult to assess, various elements of the design of parking
      facilities may have an influence on the occurrence of injuries.

PMID- 18325412
TI  - Teaching adolescents safe driving and passenger behaviors: effectiveness of the
      You Hold the Key Teen Driving Countermeasure.
AB  - PROBLEM: Unsafe driving and passenger behaviors place teens at increased risk for
      fatal and nonfatal crashes. This study evaluated the short-and long-term efficacy
      of the You Hold the Key (YHTK) Teen Driving Countermeasure. METHOD: A two-page
      survey was completed by high school students at pretest, posttest, and long-term
      (6-month) posttest. RESULTS: YHTK was associated with significant immediate and
      long-term improvements in teen seatbelt use, safe driving, and perceived
      confidence in preventing drunk driving. Compared to pretests, students at
      immediate and long-term posttest more frequently wore seatbelts when driving or
      riding, required passengers to wear seatbelts, and limited the number of
      passengers to the number of seatbelts in the vehicle. Students were more likely
      at both posttests to avoid drinking and driving and to say no to riding with a
      friend who had been drinking. SUMMARY: YHTK was associated with increases in safe
      teen driving and passenger behaviors. IMPACT ON INDUSTRY: Success of YHTK is most
      notably due to its comprehensive nature. Future programs should consider
      comprehensive strategies when attempting to modify teen behaviors.

PMID- 18325413
TI  - Child passenger restraint use and emergency department--reported injuries: a
      special study using the National Electronic Injury Surveillance System-All Injury
      Program, 2004.
AB  - INTRODUCTION: In 2004, more than 180,000 child passengers aged <or=12 years
      sought care in U.S. hospital emergency departments (EDs) for injuries sustained
      in motor-vehicle crashes (MVCs). METHOD: We expanded the National Electronic
      Injury Surveillance System-All Injury Program for 635 injured children aged
      <or=12 years treated at 15 hospital EDs in 2004 by collecting multiple injury
      diagnoses and interviewing parents about MVC circumstances. RESULTS: Nine percent
      of the children were unrestrained and 36% were inappropriately restrained. Blacks
      and Hispanics were about six times more likely to be unrestrained than Non
      Hispanic Whites (12% and 14%, respectively, vs. 2%). Seventy-seven percent of
      inappropriate restraint use occurred among children aged 4-8 years, who were
      prematurely placed in seatbelts. Eight percent of children required
      hospitalization; unrestrained children were three times more likely to be
      hospitalized than restrained children (21% vs. 7%). CONCLUSION: Age-appropriate
      restraint use should be promoted for child passengers, particularly among Blacks,
      Hispanics, and children riding in trucks.

PMID- 18325414
TI  - Regional economic conditions and crash fatality rates--a cross-county analysis.
AB  - INTRODUCTION: Most studies that evaluate the relationship between economic
      conditions and traffic fatalities focus on the time-series relationship between
      the two factors. This analysis considers the cross-sectional perspective by
      estimating the cross-county correlation between per capita income and fatalities
      per vehicle mile traveled (VMT) in Ohio. METHOD: The empirical model employed in
      this analysis allows for interaction effects between per capita income and
      highway usage, in the determination of fatality rates. RESULTS: The resultant
      least squares estimates indicate that a significant interaction effect exists
      between per capita income and the percentage of highway VMT, indicating a
      nonlinear correlation between per capita income and fatality rates. This
      correlation rises as the proportion of VMT on highways rises, such that there is
      an inverse relationship with fatality rates when the highway share of county VMT
      is low and a direct relationship with fatality rates when the highway share of
      county VMT is high. Additionally, population density, the presence of interstate
      highways in rural counties, the prior prevalence of severe alcohol abuse, and the
      proportion of teen drivers all proved to be significant correlates with county
      fatality rates. CONCLUSIONS: These observations suggest factors that state and
      federal policy makers should consider when allocating resources that impact
      (whether directly or indirectly) traffic fatalities.

PMID- 18325415
TI  - The relation of non-culpable traffic incidents to bus drivers' celeration
      behavior.
AB  - PROBLEM: The driver celeration behavior theory predicts that celerations are
      associated with incidents for which the driver has some responsibility in
      causing, but not other incidents. METHOD: The hypothesis was tested in 25 samples
      of repeated measurements of bus drivers' celeration behavior against their
      incidents for two years. RESULTS: The results confirmed the prediction; in 18
      samples, the correlation for culpable incidents only was higher than for all
      incidents, despite the higher means of the latter. Non-culpable incidents had
      correlations close to zero with celeration. DISCUSSION: It was pointed out that
      most individual crash prediction studies have not made this differentiation, and
      thus probably yielded underestimates of the associations sought, although the
      effect is not strong, due to non-culpable accident involvements being few (less
      than a third of the total). The methods for correct identification of culpable
      incident involvements were discussed.

PMID- 18325416
TI  - Crashes of novice teenage drivers: characteristics and contributing factors.
AB  - OBJECTIVE: The initial months of licensure are especially hazardous for
      teenagers. Factors leading to crashes of novice 16-year-old drivers were
      identified. METHOD: Sixteen year-olds in Connecticut who were involved in
      nonfatal crashes during the first 8 months of licensure were interviewed, and
      police crash reports were examined. Crash types and contributing factors were
      identified. RESULTS: Three-fourths of the crash-involved teenagers were at fault.
      Their crashes resulted primarily when they ran off the road, rear ended another
      vehicle, or collided with another vehicle that had the right-of-way. Three
      factors contributed about equally to their crashes: failing to detect another
      vehicle or traffic control, speeding, and losing control of the vehicle or
      sliding. Slippery roads also were an important factor. Most failures to detect
      another vehicle or traffic control involved not looking thoroughly, distraction,
      or inattention. DISCUSSION: Based on the findings, potential countermeasures for
      reducing crashes of novice teenage drivers include adequate practice driving, in
      vehicle monitoring devices, and electronic stability control. IMPACT ON INDUSTRY:
      More than half of the nonfatal, at-fault crashes of newly licensed 16-year-old
      drivers involved more than one contributing factor including speed, loss of
      control, and slippery roads. Efforts to reduce teenage crashes should focus on
      these factors.

PMID- 18325417
TI  - Measuring determinants of occupational health related behavior in Flemish
      farmers: an application of the Theory of Planned Behavior.
AB  - PROBLEM: Preventive interventions to reduce occupational injuries and health
      problems in farmers require the identification of factors that contribute to
      unsafe and health damaging behavior. This paper describes the development and
      validation of a self-report questionnaire, which measures the determinants of
      occupational health-related behaviors in farmers. METHOD: A representative sample
      of 283 Flemish farmers completed a provisional 135 item questionnaire based on
      the Theory of Planned Behavior, measuring four behaviors related to occupational
      health (machinery use, animal handling, preventing falls, and pesticide use), as
      well as the intentions, attitudes, perceived social norms, and self-efficacy for
      each of these behaviors. RESULTS: The fit indices of the Confirmatory Factor
      Analysis turned out not to be sufficient to reproduce the dimensions of the TPB.
      Therefore exploratory factor analysis was use to determine the underlying
      dimensions. Principal Component Analyses (PCA) on the behavioral items yielded
      single component solutions explaining a considerable proportion of the variance
      for each behavior and for behavioral intentions. Principal component analyses
      toward an a priori three-component structure reflecting the TPB dimensions did
      not produce sufficient congruence for the determinants of the four behaviors.
      Subsequent Varimax rotations and discarding of redundant items resulted in three
      component solutions explaining 50% to 69% of the variance in the determinants of
      each behavior, corresponding with the dimensions of the TPB. Internal
      consistencies ranged from .25 to .89. Scale scores accounted for a significant
      proportion of the variance in intention and self-reported behavior. IMPACT: The
      study demonstrates the validity of the TPB in predicting behavior related to
      occupational safety and health in farmers, and provides a valid and reliable
      questionnaire to measure the cognitive concepts featured in this model. IMPACT ON
      INDUSTRY: Both authors share the same view on this study's impact on industry. In
      recent years, efforts have been made to create awareness among farmers about
      occupational hazards, and to encourage farmers to perform safer and healthier
      behavior. However, only a limited number of these interventions have proven to be
      successful. A possible reason for this relative lack of success is that
      interventions typically focus on risk analysis and raising awareness, whereas the
      literature on preventive health behavior change indicates that knowledge and
      awareness with regard to possible health risks are neither necessary nor
      sufficient to change behavior. To raise the effectiveness of prevention programs,
      other relevant determinants of behavior need to be addressed as well, such as:
      attitudes, perceived social norms, self efficacy, and elements of the physical
      environment that elicit or reinforce behavior. These determinants play a key role
      in psychological models of health related behavior, such as the Theory of Planned
      Behavior. Thus far, the use of these models within agricultural settings is
      fairly limited. This study demonstrates the validity of the Theory of Planned
      Behavior in predicting behavior related to occupational safety and health in
      farmers, and provides a valid and reliable questionnaire to measure the cognitive
      concepts featured in this model.

PMID- 18325418
TI  - The impact of environmental, vehicle and driver characteristics on injury
      severity in older drivers hospitalized as a result of a traffic crash.
AB  - INTRODUCTION: Compared to younger age groups, older people are more likely to be
      seriously injured or to die as a result of a traffic crash. METHOD: The aim of
      the study is to examine the impact of environmental, vehicle, crash, and driver
      characteristics on injury severity in older drivers involved in traffic crashes
      by using recently linked police crash records and hospitalization data from New
      South Wales, Australia. The severity of injury resulting from traffic crashes was
      measured using the International Classification of Diseases, 10th revision (ICD
      10) Injury Severity Score (ICISS). RESULTS: Multivariate analysis identified
      rurality, presence of complex intersections, road speed limit, driver error,
      speeding, and seat belt use as independent predictors of injury severity in older
      people. The type of intersection configuration explained over half of the
      observed variations in injury severity. IMPACT ON INDUSTRY: Environmental
      modification such as intersection treatments might contribute to a decrease in
      the severity of injury in older people involved in road crashes.

PMID- 18325419
TI  - The natural selection of organizational and safety culture within a small to
      medium sized enterprise (SME).
AB  - INTRODUCTION: Small to Medium Sized Enterprises (SMEs) form the majority of
      Australian businesses. METHOD: This study uses ethnographic research methods to
      describe the organizational culture of a small furniture-manufacturing business
      in southern Australia. RESULTS: Results show a range of cultural assumptions
      variously 'embedded' within the enterprise. In line with memetics - Richard
      Dawkin's cultural application of Charles Darwin's theory of Evolution by Natural
      Selection, the author suggests that these assumptions compete to be replicated
      and retained within the organization. The author suggests that dominant
      assumptions are naturally selected, and that the selection can be better
      understood by considering the cultural assumptions in reference to Darwin's
      original principles and Frederik Barth's anthropological framework of knowledge.
      The results are discussed with reference to safety systems, negative cultural
      elements called Cultural Safety Viruses, and how our understanding of this
      particular organizational culture might be used to build resistance to these
      viruses.

PMID- 18325420
TI  - A methodology to model causal relationships on offshore safety assessment
      focusing on human and organizational factors.
AB  - INTRODUCTION: Focusing on people and organizations, this paper aims to contribute
      to offshore safety assessment by proposing a methodology to model causal
      relationships. METHOD: The methodology is proposed in a general sense that it
      will be capable of accommodating modeling of multiple risk factors considered in
      offshore operations and will have the ability to deal with different types of
      data that may come from different resources. Reason's "Swiss cheese" model is
      used to form a generic offshore safety assessment framework, and Bayesian Network
      (BN) is tailored to fit into the framework to construct a causal relationship
      model. The proposed framework uses a five-level-structure model to address latent
      failures within the causal sequence of events. The five levels include Root
      causes level, Trigger events level, Incidents level, Accidents level, and
      Consequences level. To analyze and model a specified offshore installation
      safety, a BN model was established following the guideline of the proposed five
      level framework. A range of events was specified, and the related prior and
      conditional probabilities regarding the BN model were assigned based on the
      inherent characteristics of each event. RESULTS: This paper shows that Reason's
      "Swiss cheese" model and BN can be jointly used in offshore safety assessment. On
      the one hand, the five-level conceptual model is enhanced by BNs that are capable
      of providing graphical demonstration of inter-relationships as well as
      calculating numerical values of occurrence likelihood for each failure event.
      Bayesian inference mechanism also makes it possible to monitor how a safety
      situation changes when information flow travel forwards and backwards within the
      networks. On the other hand, BN modeling relies heavily on experts' personal
      experiences and is therefore highly domain specific. IMPACT ON INDUSTRY: "Swiss
      cheese" model is such a theoretic framework that it is based on solid behavioral
      theory and therefore can be used to provide industry with a roadmap for BN
      modeling and implications. A case study of the collision risk between a Floating
      Production, Storage and Offloading (FPSO) unit and authorized vessels caused by
      human and organizational factors (HOFs) during operations is used to illustrate
      an industrial application of the proposed methodology.

PMID- 18325421
TI  - The effects of mobile speed camera introduction on road traffic crashes and
      casualties in a rural county of England.
AB  - PROBLEM: This study assesses the impact of crash and casualty numbers in
      correspondence to the introduction of mobile speed cameras in the rural county of
      Norfolk, England. METHOD: Road traffic accident casualty and crash data were
      collected for two years before the introduction of cameras and two years
      subsequently. The casualties and crashes occurring at 29 camera sites were
      identified and separated from those occurring in the rest of the county. Trends
      in crashes and casualties, and their severity, were examined graphically and
      comparisons were made between before and after periods. The regression to the
      mean effect at individual sites was estimated. RESULTS: After the introduction of
      cameras, overall crashes declined by 1% and crashes involving fatalities or
      serious injuries declined by 9% on the roads without cameras. At the camera
      sites, crashes decreased by 19% and fatal and serious crashes by 44%. The
      reduction in total crashes was significantly greater than that expected from the
      effect of regression to the mean in 12 out of 20 sites tested. SUMMARY: The
      introduction of cameras appears to have resulted in real and measurable
      reductions in crash risk in this rural county. IMPACT ON INDUSTRY: Our results
      suggest the deployment of mobile speed cameras is an effective tool for
      organizations wishing to reduce road traffic casualties in areas where high crash
      rates have been associated with excessive vehicle speeds.

PMID- 18325422
TI  - Hyponatremia in neurosurgical patients.

PMID- 18325424
TI  - Cerebral salt wasting and elevated brain natriuretic peptide levels after
      traumatic brain injury: 2 case reports.
AB  - BACKGROUND: Historically, hyponatremia in patients with varying brain diseases
      was termed cerebral salt wasting. Hyponatremia secondary to CSW was reported to
      be a distinct entity from SIADH, with the distinguishing feature of decreased
      extracellular fluid volume. Brain natriuretic peptide, a peptide with
      natriuretic, vasorelaxant, and aldosterone-inhibiting properties, was recently
      implicated in aneurysmal SAH patients with CSW. Here, we describe 2 cases of CSW
      in TBI patients with elevated BNP levels. This phenomenon has not been previously
      described. CASE DESCRIPTION: Two patients with TBI and hyponatremia were subject
      to analysis. Central lines were placed to assess volume status. Levels of BNP
      were measured at the onset of hypertonic saline infusion. Electrocardiogram and
      cardiac enzyme studies were performed to assess cardiac function. Serial imaging
      was performed to assess the extent of brain injury. CONCLUSIONS: These patients
      with TBI had findings consistent with CSW with elevated BNP levels in the setting
      of normal cardiac function. In both cases, a high BNP level was observed after
      declining plasma Na levels despite aggressive hypertonic saline infusion. High
      BNP levels may be associated with CSW. Further studies are necessary to establish
      a causative role for BNP in TBI-induced CSW.

PMID- 18325425
TI  - Cerebral salt wasting after traumatic brain injury: an important critical care
      treatment issue.

PMID- 18325426
TI  - Surgical outcomes of elderly patients with cervical spondylotic myelopathy.
AB  - BACKGROUND: Cervical spondylotic myelopathy is a potentially serious neurologic
      disorder that commonly presents with gait difficulty and hand dysfunction.
      Because the development of CSM is in large part related to advanced spondylosis
      and degenerative disk disease, elderly patients appear to be at an increased risk
      to develop this condition. The surgical outcomes of this patient population have
      been understudied; the authors seek to report their clinical results in a series
      of patients with CSM older than 75 years who underwent surgical treatment.
      METHODS: This report is composed of a cohort of 36 elderly patients (older than
      75 years) and 34 younger patients (younger than 65 years) who underwent
      decompressive surgery for CSM at one institution between 2001 and 2005. The
      patients' functional status was evaluated preoperatively and postoperatively
      using the mJOA disability scale. RESULTS: The mean follow-up time in the elderly
      group was 24 months, with a range from 12 to 48 months. There was a statistically
      significant improvement between mean preoperative (11.3) and postoperative (14.4)
      mJOA scores (P< .0001). The younger group had a higher neurologic recovery rate
      (71%) than the elderly group (59%); however, this was not statistically
      significant (P= .29). The postoperative complication rate in the elderly
      population (38%) was higher than in the younger group (6%; P= .002). CONCLUSION:
      Elderly patients with CSM are likely to obtain neurologic improvement after
      decompressive surgery. Their postoperative complication rate is higher than that
      of younger patients, yet most complications appear to be self limiting and do not
      adversely affect neurologic outcome.

PMID- 18325427
TI  - Traumatic epidural hematomas of the posterior cranial fossa.
AB  - BACKGROUND: Traumatic EDHs of the posterior cranial fossa are rare and have a
      higher mortality than supratentorial localizations. Early diagnosis of TEHPCF and
      prompt surgical evacuation provide excellent recovery. Active use of cranial CT
      scanning has taken a major role in the diagnosis, surgical indication, close
      observation, and strategy planning. As a result, better prognosis is achieved. In
      this study, we represent our results and experiences in the management of TEHPCF.
      METHODS: Between 1993 and 2006, 65 patients with TEHPCF were treated in Istanbul
      University Faculty Of Medicine, Neurosurgery and Emergency Surgery Departments.
      The hospital records of these patients were analyzed retrospectively. RESULTS: Of
      65 patients, whose diagnosis and management decisions were determined by cranial
      CT scans, 53 were treated through surgery and 12 by conservative methods. Of the
      53 surgically treated patients, 2 (3%) patients died, and 2 (3%) other patients
      remained moderately disabled during their discharge. As a result, 61 (94%) of 65
      patients had excellent recovery. CONCLUSION: When compared with the literature,
      our mortality rate was superior to other previously reported studies. In our
      opinion, this is a result of extensive use of the cranial CT scan together with
      aggressive surgery. Patients with occipital trauma should be evaluated using
      cranial CT scans, and those showing mass effect should be immediately treated
      surgically. The patients that have no mass effect on CT scans can be closely
      observed by planned serial control CT scans.

PMID- 18325429
TI  - Whose life is it anyway?

PMID- 18325431
TI  - Profiles in volunteerism: Dr William B. Walsh and the SS HOPE.

PMID- 18325432
TI  - Cutaneous lymphoma. Foreword.

PMID- 18325433
TI  - Cutaneous lymphoma.

PMID- 18325434
TI  - The challenge of CPR quality: improvement in the real world.

PMID- 18325435
TI  - Optimal treatment of carotid artery disease.
AB  - Extracranial carotid artery disease accounts for approximately 25% of ischemic
      strokes. Although carotid endarterectomy (CEA) is the established gold standard
      for carotid revascularization, carotid artery angioplasty and stenting (CAS) is
      continually developing into a safer and more efficacious method of stroke
      prevention. Embolic protection, improving stent designs, and ever-increasing
      surgeon experience are propelling CAS towards equipoise with and possible
      superiority to CEA. One multicenter randomized trial and several nonrandomized
      registries have successfully established CAS as an accepted treatment for high
      risk patients. Clinicians must strive to perform well-designed clinical trials
      that will continue to aid understanding and improve application of both
      endovascular and open techniques for extracranial carotid revascularization. We
      review the data published to date regarding the indications for and recent
      developments in the use of CAS.

PMID- 18325436
TI  - Drug-eluting stent thrombosis: results from the multicenter Spanish registry
      ESTROFA (Estudio ESpanol sobre TROmbosis de stents FArmacoactivos).
AB  - OBJECTIVES: This study sought to assess the incidence, predictors, and outcome of
      drug-eluting stent(DES) thrombosis in real-world clinical practice. BACKGROUND:
      The DES thromboses in randomized trials could not be comparable to those observed
      in clinical practice, frequently including off-label indications. METHODS: We
      designed a large-scale, nonindustry-linked multicentered registry, with 20
      centers in Spain. The participant centers provided follow-up data for their
      patients treated with DES, reporting a detailed standardized form in the event of
      any angiography-documented DES-associated thrombosis occurring. RESULTS: Of
      23,500 patients treated with DES, definite stent thrombosis(ST) developed in 301:
      24 acute, 125 subacute, and 152 late. Of the late, 62 occurred >1 year(very late
      ST). The cumulative incidence was 2% at 3 years. Antiplatelet treatment had been
      discontinued in 95 cases(31.6%). No differences in incidences were found among
      stent types. Independent predictors for subacute ST analyzed in a subgroup of
      14,120 cases were diabetes, renal failure, acute coronary syndrome, ST-segment
      elevation myocardial infarction, stent length, and left anterior descending
      artery stenting, and for late ST were ST-segment elevation myocardial infarction,
      stenting in left anterior descending artery, and stent length. Mortality at 1
      year follow-up was 16% and ST recurrence 4.6%. Older age, left ventricular
      ejection fraction <45%, nonrestoration of Thrombolysis In Myocardial Infarction
      flow grade 3, and additional stenting were independent predictors for mortality.
      CONCLUSIONS: The cumulative incidence of ST after DES implantation was 2% at 3
      years. No differences were found among stent types. Patient profiles differed
      between early and late ST. Short-term prognosis is poor, especially when
      restoration of normal flow fails.

PMID- 18325437
TI  - Cockcroft-Gault versus modification of diet in renal disease: importance of
      glomerular filtration rate formula for classification of chronic kidney disease
      in patients with non-ST-segment elevation acute coronary syndromes.
AB  - OBJECTIVES: Our purpose was to compare formulae for estimating glomerular
      filtration rate (GFR) in non-ST-segment elevation acute coronary syndromes (NSTE
      ACS) patients. BACKGROUND: Assessment of GFR is important for antithrombotic dose
      adjustment in NSTE ACS patients. METHODS: We assessed estimated glomerular
      filtration rate (eGFR) with Cockcroft-Gault (C-G) and Modification of Diet in
      Renal Disease (MDRD) formulae in 46,942 NSTE ACS patients from 408 CRUSADE (Can
      Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes
      with Early implementation of the American College of Cardiology/American Heart
      Association Guidelines) hospitals. Formula agreement was shown continuously and
      by chronic kidney disease (CKD) stages. We determined in-hospital outcomes and
      the association between antithrombotic dose adjustment and bleeding for moderate
      CKD as determined by each formula. RESULTS: The median (interquartile range
      [IQR]) eGFR was 53.2 ml/min (34.7, 75.1 ml/min) by C-G and 65.8 ml/min (47.6,
      83.5 ml/min) by MDRD. The mean eGFR was higher with MDRD (approximately 9.1
      ml/min), but this difference was greater in age, weight, and gender subgroups.
      Chronic kidney disease classification differed in 20% of the population and
      altered when antithrombotic dose adjustment was required by C-G versus MDRD
      (eptifibatide: 45.7% vs. 27.3%; enoxaparin: 19.0% vs. 9.6%). CONCLUSIONS:
      Important CKD disagreements occur in approximately 20% of acute coronary syndrome
      patients, affecting dosing adjustments in those already susceptible to bleeding.
      Dosing based on C-G formula is preferable, particularly in the small, female, or
      elderly patient.

PMID- 18325438
TI  - Prognostic role of flow-mediated dilation and cardiac risk factors in post
      menopausal women.
AB  - OBJECTIVES: The aim of this study was to examine the association between brachial
      artery flow-mediated dilation (FMD) and cardiovascular events in a cohort of
      initially asymptomatic post-menopausal women, with adjustment for the presence of
      the major cardiovascular risk factors. BACKGROUND: Conventional major
      cardiovascular risk factors (cigarette smoking, hypercholesterolemia,
      hypertension, and diabetes) fail to explain nearly 50% of cardiovascular events.
      Defining the magnitude of future risk for the development of clinical events is a
      major focus of effective primary prevention. Evaluation of endothelial function,
      utilizing the noninvasive measurement of the brachial artery FMD, may serve as a
      screening tool to individualize high-risk patients. METHODS: We conducted a
      prospective study on 2,264 post-menopausal women, age 54 +/- 6 years. The length
      of the follow-up was 45 +/- 13 months (range 6 to 65 months). RESULTS: During
      observation, 90 major events were recorded. Risk-adjusted relative risk values
      resulted 1.0, 1.33 (95% confidence interval [CI] 1.09 to 4.09), and 4.42 (95% CI
      2.97 to 8.01) for women in the higher, intermediate, and lower tertile of FMD,
      respectively (p < 0.0001 for trend). The event rate for women in the lower
      tertile (FMD <or=4.5%) was greater than the combined event rate noted in the
      other 2 tertiles (women in the lower tertile accounted for 51 events [56.6% of
      total events]). When added to age and other conventional cardiovascular risk
      factors (smoking habits, presence of hypercholesterolemia, history of diabetes,
      hypertension), FMD contributed significantly to the model predicting
      cardiovascular events (likelihood ratio chi-square change: 10.22; p < 0.0001).
      CONCLUSIONS: In post-menopausal women, the knowledge of FMD provided incremental
      prognostic information regarding the risk of developing cardiovascular events.

PMID- 18325439
TI  - Characterization of electrograms associated with termination of chronic atrial
      fibrillation by catheter ablation.
AB  - OBJECTIVES: This study sought to determine the characteristics of atrial
      electrograms predictive of slowing or termination of atrial fibrillation (AF)
      during ablation of chronic AF. BACKGROUND: There is growing recognition of a role
      for electrogram-based ablation. METHODS: Forty consecutive patients (34 male, 59
      +/- 10 years) undergoing ablation for chronic AF persisting for a median of 12
      months (range 1 to 84 months) were included. After pulmonary vein isolation and
      roof line ablation, electrogram-based ablation was performed in the left atrium
      and coronary sinus. Targeted electrograms were acquired in a 4-s window and
      characterized by: 1) percentage of continuous electrical activity; 2) bipolar
      voltage; 3) dominant frequency; 4) fractionation index; 5) mean absolute value of
      derivatives of electrograms; 6) local cycle length; and 7) presence of a temporal
      gradient of activation. Electrogram characteristics at favorable ablation
      regions, defined as those associated with slowing (a >or=6-ms increase in AF
      cycle length) or termination of AF were compared with those at unfavorable
      regions. RESULTS: The AF was terminated by electrogram-based ablation in 29
      patients (73%) after targeting a total of 171 regions. Ablation at 37 (22%) of
      these regions was followed by AF slowing, and at 29 (17%) by AF termination. The
      percentage of continuous electrical activity and the presence of a temporal
      gradient of activation were independent predictors of favorable ablation regions
      (p = 0.016 and p = 0.038, respectively). Other electrogram characteristics at
      favorable ablation regions were not significantly different from those at
      unfavorable ablation regions. CONCLUSIONS: Catheter ablation at sites displaying
      a greater percentage of continuous activity or a temporal activation gradient is
      associated with slowing or termination of chronic AF.

PMID- 18325440
TI  - Atrial fibrillation catheter ablation: learning by burning continues.

PMID- 18325441
TI  - Prevalence of American Heart Association type VI carotid atherosclerotic lesions
      identified by magnetic resonance imaging for different levels of stenosis as
      measured by duplex ultrasound.
AB  - OBJECTIVES: Via magnetic resonance imaging (MRI), we sought to determine the
      prevalence of atherosclerotic American Heart Association type VI lesions (AHA
      LT6) (lesions with luminal surface defect, hemorrhage/thrombus, or calcified
      nodule) in carotid arteries that represented all categories of stenosis as
      measured by duplex ultrasound. BACKGROUND: Arterial stenosis alone has been shown
      to be a poor predictor of cardiovascular events. Autopsy studies suggest that
      features associated with AHA-LT6 lesions, rather than the degree of luminal
      narrowing, characterize the high-risk plaque. METHODS: A total of 192 subjects
      underwent bilateral carotid artery magnetic resonance imaging (MRI) scans at 1.5T
      after evaluation with ultrasound to determine stenosis. After excluding arteries
      with a previous endarterectomy, poor image quality, or missing ultrasound data,
      there were 175 patients with 260 arteries available for analysis. The AHA lesion
      type was determined by the consensus opinion of 2 experienced carotid MRI
      reviewers. RESULTS: In total, 96 of 260 (37.0%) arteries had >or=1 location with
      AHA-LT6. Of the arteries with AHA-LT6, 84.4% had hemorrhage, 45.8% had a ruptured
      fibrous cap, and 14.6% showed other type of complications. Prevalence of AHA-LT6
      was an increasing sequence of 8.1% in the 37 arteries with 1% to 15% stenosis,
      21.7% in the 60 arteries with 16% to 49% stenosis, 36.8% in the 114 arteries with
      50% to 79% stenosis, and 77.6% in the 49 arteries with 80% to 99% stenosis.
      CONCLUSIONS: Complicated AHA-LT6 are frequently found in arteries with <or=50%
      stenosis. These findings indicate that complex lesions develop in a substantial
      number of arteries in the absence of high-grade stenosis. Ongoing prospective
      studies will determine the predictive value of vulnerable plaque features, as
      visualized by MRI, for risk of subsequent ischemic events.

PMID- 18325442
TI  - Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis:
      noninvasive imaging compared to endomyocardial biopsy.
AB  - OBJECTIVES: We sought to evaluate the diagnostic performance of cardiovascular
      magnetic resonance imaging (CMRI) for detection of cardiac amyloidosis compared
      with endomyocardial biopsy (EMB) in a clinical routine setting. BACKGROUND: For
      the clinical workup of heart failure with restrictive filling, pattern cardiac
      amyloidosis is an important differential diagnosis that is difficult to verify
      with current noninvasive techniques, especially in the presence of myocardial
      hypertrophy. METHODS: A total of 33 consecutive patients underwent both CMRI and
      EMB for workup of heart failure with restrictive filling pattern in combination
      with myocardial hypertrophy (n = 24) and/or clinical conditions often associated
      with cardiac amyloidosis (n = 18). RESULTS: Cardiac amyloidosis was detected by
      EMB in 15 of the 33 patients. In patients with biopsy-proven cardiac amyloidosis,
      CMRI revealed a distinct pattern of late gadolinium enhancement, which was
      distributed over the entire subendocardial circumference, extending in various
      degrees into the neighboring myocardium. This pattern was found in 12 of the 15
      patients diagnosed with cardiac amyloidosis by EMB, compared with only 1
      individual in the group of 18 patients diagnosed with other myocardial diseases.
      Consequently, using this pattern as a diagnostic criterion, the sensitivity of
      CMRI for diagnosing cardiac amyloidosis was 80%, yielding a specificity of 94%.
      The positive predictive value was 92%, and the negative predictive value was 85%.
      CONCLUSIONS: In patients with biopsy-proven cardiac amyloidosis, late gadolinium
      enhancement frequently occurs in a peculiar pattern. On the basis of the gold
      standard, EMB, noninvasive CMRI can be used to diagnose or rule out cardiac
      amyloidosis with good sensitivity and excellent specificity in a clinical routine
      setting.

PMID- 18325443
TI  - Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis:
      diagnostic value of a typical pattern of late gadolinium enhancement.

PMID- 18325444
TI  - Prevalence of hypertrophic cardiomyopathy in highly trained athletes: relevance
      to pre-participation screening.
AB  - OBJECTIVES: This study sought to determine the prevalence of hypertrophic
      cardiomyopathy (HCM) in elite athletes. BACKGROUND: Hypertrophic cardiomyopathy
      is considered to be the most common cause of exercise-related sudden death in
      young athletes. The prevalence of HCM in elite athletes has never been reported
      but has important implications with regard to pre-participation screening for the
      disorder. METHODS: Between 1996 and 2006, 3,500 asymptomatic elite athletes (75%
      male) with a mean age of 20.5 +/- 5.8 years (range 14 to 35 years) underwent 12
      lead electrocardiography and 2-dimensional echocardiography. None had a known
      family history of HCM. RESULTS: Of the 3,500 athletes, 53 (1.5%) had left
      ventricular hypertrophy (mean 13.6 +/- 0.9, range 13 to 16), and of these 50 had
      a dilated left ventricular cavity with normal diastolic function to indicate
      physiological left ventricular hypertrophy. Three (0.08%) athletes with left
      ventricular hypertrophy had a nondilated left ventricular cavity and associated
      deep T-wave inversion that could have been consistent with HCM. However, none of
      the 3 athletes had any other phenotypic features of HCM on further noninvasive
      testing and none had first-degree relatives with features of HCM. One of the 3
      athletes agreed to detrain for 12 weeks, which showed resolution of
      electrocardiography and echocardiographic changes confirming physiologic left
      ventricular hypertrophy. CONCLUSIONS: The prevalence of HCM in highly trained
      athletes is extremely rare. Structural and functional changes associated with HCM
      naturally select out most individuals from competitive sports. Screening athletes
      with echocardiography is not cost effective. However, electrocardiography is
      useful in selecting out those individuals who may have pathological left
      ventricular hypertrophy for subsequent echocardiography.

PMID- 18325445
TI  - Athlete screening for occult cardiac disease: no risk, no fun?

PMID- 18325446
TI  - President's page: responding to the drum beat for health care reform.

PMID- 18325447
TI  - Left ventricular unloading in acute ST-segment elevation myocardial infarction
      patients is safe and feasible and provides acute and sustained left ventricular
      recovery.

PMID- 18325448
TI  - Role of percutaneous coronary minimalist intervention in the management of acute
      ST-segment elevation myocardial infarction.

PMID- 18325449
TI  - Prophylactic use of hemodialysis to prevent radiocontrast-induced nephropathy:
      the discussion is open again!

PMID- 18325452
TI  - Rates of medial tibiofemoral joint space narrowing in osteoarthritis studies
      consistent despite methodological differences.
AB  - RATIONALE: Minimum tibiofemoral joint space width in the medial compartment (JSW)
      is the most well-established structural outcome measure for osteoarthritis (OA)
      of the knee. Its usefulness as a measure of therapeutic effectiveness in short
      term studies is limited by the rate and variability of joint space narrowing
      (JSN) in the OA population. Microfocal radiography has been shown to improve
      reproducibility of JSW measurement compared to standard radiography, but
      measurement of magnification from microfocal knee films has been problematic, and
      JSN is yet to be investigated in a longitudinal microfocal study. OBJECTIVE: To
      establish the effect on JSW reproducibility of a new method of magnification
      measurement in microfocal radiographs. To report on and compare rates of medial
      tibiofemoral JSN and their variations in the placebo arms of microfocal and
      standard radiographic clinical trials in OA, using fluoroscopic semi-flexed (SF)
      knee positioning. To place in the context of published estimates of rates of JSN
      from comparable studies. METHODS: Using microfocal radiography, 36 patients were
      followed at a single centre for 2 years. Using standard radiography, 86 patients
      were followed for 1 year at a single centre, and 549 for 2 years in a multi
      centre international study. Computerised JSW measurement was undertaken using
      enhanced and automated versions of existing algorithms. Rates of JSN were
      examined in the context of a review of published rates of JSN using a variety of
      techniques. RESULTS: Reproducibility of JSW measurement from microfocal
      radiographs was improved by the new magnification measurement. Rates of JSN were
      similar across the studies, but more variable when using standard radiography.
      The rates of JSN were also consistent with those from previously published
      investigations; all estimates since 2000, bar one, being consistent with the
      value 0.05 mm/year. CONCLUSION: Microfocal radiography using the new method
      lowered the variability of the rate of JSN, but the high cost and low
      availability of microfocal equipment remains a barrier to its more widespread
      use. The consistently low but highly variable rates of JSN seen in the review
      suggest that continued attempts to improve radiographic and mensural techniques
      are unlikely to significantly reduce required sample sizes.

PMID- 18325453
TI  - The "gap" between bench and bedside: widening or narrowing?

PMID- 18325454
TI  - Incremental survival benefit with adherence to standardized heart failure core
      measures: a performance evaluation study of 2958 patients.
AB  - BACKGROUND: In 2002, the Joint Commission on Accreditation of Healthcare
      Organizations (JCAHO) established four heart failure (HF) core measures to
      standardize and improve health care quality in the United States. Although
      adherence to these HF care processes may be improving, their collective impact on
      survival is not yet settled. METHODS: JCAHO HF measures were implemented within a
      20-hospital health care system. Eligible patients had a principal discharge
      diagnosis of HF. Metrics representing compliance with these measures were derived
      and their relationship with 1-year survival was examined using an adjusted Cox
      proportional hazards regression. RESULTS: A total of 2958 patients met study
      criteria. The average age was 73 years, 50% were male, and 9.9% were smokers. One
      year survival benefits were seen in an item-by-item evaluation of HF measures for
      angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy
      (hazard ratio [HR] = 0.69), left ventricular function assessment (HR = 0.83), and
      patient education (HR = 0.79). When assessed collectively, improved survival was
      seen among patients eligible for two (HR = 0.53), three (HR = 0.36), or four HF
      measures (HR = 0.65). Further, we found a positive and incremental relationship
      between the degree of adherence and survival (P = .008). CONCLUSION: Adherence to
      JCAHO HF core measures is associated with improved 1-year survival after HF
      hospitalization. This validates these simple and effective performance measures
      and justifies efforts to implement them in all eligible patients with HF.

PMID- 18325455
TI  - Health care quality improvement: the devil really is in details.

PMID- 18325456
TI  - Communication and decision-making about prognosis in heart failure care.
AB  - BACKGROUND: Therapies to prolong life and improve quality of life for heart
      failure (HF) have expanded in both number and complexity. Clinicians, patients,
      and families are faced with an array of decisions about interventions with
      complex risks and benefits. Physicians must also discuss prognosis of HF and its
      inherent uncertainties. METHODS AND RESULTS: This article applies knowledge of
      participatory decision-making and communication about prognosis from other health
      care settings to HF care. Strategies should generally follow an "ask-tell-ask"
      format, beginning with a patient's understanding of his or her HF, identifying
      the information a patient desires, and then giving them small amounts of
      information at any given time, asking for feedback to clarify understanding.
      CONCLUSIONS: Despite the inherent uncertainty in individual outcomes with heart
      failure, physicians should discuss prognosis as desired by the patient or as
      needed to plan care, particularly when anticipated survival is shorter than 1
      year. Exploring and reflecting patient responses and attending to their emotions
      can decrease patient anxiety and promote shared decision-making.

PMID- 18325457
TI  - Patients differ in their ability to self-monitor adherence to a low-sodium diet
      versus medication.
AB  - OBJECTIVE: Poor adherence to a low-sodium diet (LSD) and prescribed medications
      increases rehospitalization risk in patients with heart failure (HF). Clinicians
      have difficulty assessing adherence objectively, so they depend on patients' self
      report. The degree to which self-reported adherence reflects actual adherence is
      unclear. We examined patients' ability to self-monitor adherence to an LSD and
      medications by comparing self-reported adherence with objective evidence of
      adherence. METHODS: A total of 133 patients with HF (male 71%; ejection fraction
      35% +/- 14%) completed the Medical Outcomes Study Specific Adherence Scale.
      Adherence to the LSD and medication were assessed objectively using 24-hour
      urinary sodium excretion and dose counting with an electronic monitoring device,
      respectively. On the basis of self-report, patients were divided into adherent
      and non-adherent groups and evaluated for differences according to objective
      adherence. RESULTS: There were no differences in urinary sodium levels between
      the self-reported LSD adherent and non-adherent groups (4560 mg vs. 4333 mg; P =
      .59). Self-reported adherent and non-adherent medication groups took 92.4% and
      80.4% of prescribed doses, respectively (P < .001). CONCLUSION: Patients were
      able to accurately estimate adherence to medication, but they failed to estimate
      LSD adherence. This finding suggests that we need to improve our means of
      evaluating adherence to the LSD and of educating patients more thoroughly about
      following the LSD. We speculated that the inability to estimate LSD adherence may
      be the result of gaps in patients' knowledge that preclude accurate self
      assessment.

PMID- 18325458
TI  - Managing heart failure care using an internet-based telemedicine system.
AB  - BACKGROUND: Managing patients with heart failure (HF) is labor intensive, and
      follow-up is often inadequate to detect day-to-day changes that ultimately lead
      to decompensation. We tested the effect of an Internet-based telemedicine (T)
      system that provides frequent surveillance and increased communicate between HF
      patients and their provider on frequency of hospitalization in a cohort of
      patients with advanced HF. METHODS AND RESULTS: HF patients in NYHA Class II-IV
      were randomized to usual care (UC, n = 24) or T (T plus UC, n = 24) and followed
      for 1 year. Office visits, emergency department visits, hospitalizations,
      telephone calls, and number of Internet communications were measured over the 1
      year period. Left ventricular ejection fraction (EF) was assessed by
      echocardiography in both groups. For T, mean age was 53.2 +/- 2.0 years (72%
      male, 61% Caucasian, 39% African American). For UC, mean age was 54.1 +/- 2.6
      years (76% male, 72% Caucasian, 14% African American, and 14% Hispanic). HF
      etiologies and EF were similar in both groups. During the 12-month period, UC had
      74 total phone calls to the practice, whereas T had 88 telephone calls plus 1887
      telemedicine data messages (6.5 messages/patient/month). ER visits were lower in
      the T group (T 5, UC 12; P < .05). Hospital admissions (T 24, C 40; P = .025) and
      total hospital days (T 84, UC 226 days; P < .005) were lower in T. Unscheduled
      clinic visits (T 13, UC 13; P = NS) and scheduled clinic visits (T 78, UC 94; P =
      NS) were similar in both groups. CONCLUSIONS: Frequent monitoring and patient
      management using a telemedicine system may help to reduce hospitalizations,
      hospital days, and emergency department visits.

PMID- 18325459
TI  - Venous thromboembolism prophylaxis in hospitalized heart failure patients.
AB  - BACKGROUND: Venous thromboembolism (VTE) is a concerning problem for hospitalized
      heart failure (HF) patients. Current recommendations are that all hospitalized
      New York Heart Association Class III or IV HF patients should receive VTE
      prophylaxis. Our purpose was to describe the rate of use and the characteristics
      of patients receiving VTE prophylaxis in the Acute Decompensated Heart Failure
      National Registry (ADHERE). METHODS AND RESULTS: HF hospitalization episodes in
      ADHERE were analyzed. Patients were excluded from analysis if they were receiving
      Coumadin or intravenous heparin, had elevated troponin levels, underwent cardiac
      catheterization or dialysis before or during hospitalization, or were initially
      admitted to the intensive care unit. VTE prophylaxis was defined as low-molecular
      weight or subcutaneous unfractionated heparin administered at any time during
      hospitalization and intravenous vasoactive therapy was defined as any inotrope,
      inodilator, or vasodilator. Chi-square, analysis of variance, and Wilcoxon tests
      were used for univariate and multivariate analyses. Logistic regression was used
      to evaluate outcomes. A total of 155,073 entries were evaluated, with 71,376
      eligible for VTE prophylaxis; 21,847 (31%) received VTE prophylaxis. VTE
      prophylaxis patients were more often African American (28% versus 21%) or
      admitted from the emergency department (84% versus 79%), compared with those who
      did not receive VTE prophylaxis (both P < .0001). Medical history and initial
      presentation characteristics were similar, except edema, which was more likely in
      VTE prophylaxis patients (71% versus 66%, P < .0001). Patients receiving VTE
      prophylaxis more often received an intravenous vasoactive agent (23% versus 18%),
      angiotensin-converting enzyme inhibitor (61% versus 54%), or beta-blocker (63%
      versus 58%) during their hospitalization and were more likely discharged on an
      angiotensin-converting enzyme inhibitor (53% versus 49%) or beta-blocker (57%
      versus 54%) than non-VTE prophylaxis patients, all P < .0001. VTE prophylaxis
      patients were more often admitted to the intensive care unit (4.8% versus 2.5%, P
      < .0001) and had longer median hospital stays (4.2 versus 3.8 days, P < .0001).
      Mortality was similar between cohorts (3.0% versus 2.9%, P = .69). CONCLUSIONS:
      Despite recommendations that all hospitalized New York Heart Association III and
      IV CHF patients receive venous thromboembolic disease prophylaxis, less than one
      third of eligible patients receive this guideline recommended therapy.

PMID- 18325460
TI  - Soluble Receptor for advanced glycation end products (RAGE) is a prognostic
      factor for heart failure.
AB  - BACKGROUND: We recently reported that serum levels of pentosidine, one of the
      well-defined advanced glycation end products (AGE), was an independent prognostic
      factor for heart failure. Receptor for AGEs (RAGE) is expressed in a variety of
      tissues, and RAGE has a C-truncated secretory isoform of the receptor protein,
      termed soluble RAGE. In the present study, we measured serum soluble RAGE levels
      in patients and examined whether serum soluble RAGE predicts prognosis in
      patients with heart failure. METHODS AND RESULTS: Serum soluble RAGE
      concentration was measured in 160 patients with heart failure by a competitive
      enzyme-linked immunosorbent assay. Patients were prospectively followed during a
      median follow-up period of 872 days with end points of cardiac death or
      rehospitalization. Serum soluble RAGE level increased with advancing New York
      Heart Association functional class. Serum soluble RAGE level was also higher in
      patients with cardiac events than in event free patients. From the receiver
      operating characteristic curve analysis, the cutoff value of serum soluble RAGE
      level was determined as 1220 pg/mL. Kaplan-Meier analysis clearly demonstrated
      that the high soluble RAGE group had a significantly higher incidence of cardiac
      events than occurred in the low serum soluble RAGE group (P = .0004). In the
      multivariate Cox proportional hazard analysis, soluble RAGE and serum pentosidine
      were independent risk factors for cardiac events (soluble RAGE: HR 1.90, 95% CI
      1.16-3.09, P = .010; pentosidine: HR 1.59, 95% CI 1.11-2.29, P = .012).
      CONCLUSIONS: Serum soluble RAGE level is an independent prognostic factor for
      heart failure, and this novel marker may be useful for risk stratification of
      patients with heart failure.

PMID- 18325461
TI  - Atorvastatin therapy may reduce the incidence of sudden cardiac death in patients
      with advanced chronic heart failure.
AB  - BACKGROUND: In retrospective studies, statin therapy has been related to
      decreased incidence of sudden cardiac death (SCD) in heart failure. We sought to
      prospectively investigate a relation between atorvastatin therapy and SCD in
      patients with advanced chronic heart failure. METHODS AND RESULTS: We enrolled
      110 patients with heart failure with a left ventricular ejection fraction less
      than 30% and cholesterol level greater than 150 mg/dL. Fifty-five patients were
      randomized to atorvastatin (10 mg/day) (statin group); the remaining 55 patients
      received no statins (controls). Patients were followed for 1 year. At baseline,
      the two groups did not differ in age, sex, left ventricular ejection fraction,
      cholesterol, B-type natriuretic peptide, heart rate variability, or QT
      variability. During follow-up, 29 patients died (26%) and 2 patients (2%)
      underwent heart transplantation. Of the 29 deaths, 13 were attributed to pump
      failure, 15 were attributed to SCD, and 1 was attributed to noncardiac causes.
      All-cause mortality was lower in the statin group (9/55, 16%) than in controls
      (20/55, 36%) (P = .017). The same was true of the SCD rate (3/55 [5%] vs. 12/55
      [22%], P = .012), but not of the pump failure (5/55 [9%] vs. 8/55 [15%], P =
      .38). SCD-free survival was 2.3-times higher in the statin group than in controls
      (P = .01). CONCLUSIONS: Atorvastatin therapy seems to be associated with
      decreased incidence of SCD in patients with advanced chronic heart failure.
      Larger studies are ongoing to confirm this hypothesis.

PMID- 18325462
TI  - Surgery for severe mitral regurgitation and left ventricular failure: what do we
      really know?
AB  - In ischemic and nonischemic cardiomyopathy, functional mitral regurgitation (MR)
      results from geometric abnormalities of the ventricle, which result in
      dysfunction of a morphologically normal mitral valve. Enlargement of the left
      ventricle causes geometric MR through annular dilation, increase in the
      interpapillary muscle distance, amplified leaflet tethering (elongation and
      stretch on the chordae tendinae), and decreased closing forces because of muscle
      weakness and asynchrony of papillary muscle contractile timing. The final common
      pathway of MR is a failure of coaptation of the morphologically normal leaflets
      and resultant central MR. These abnormalities can be favorably influenced by
      antiremodeling pharmacologic therapy and in selected cases by cardiac
      resynchronization therapy. Surgical repair of functional geometric MR with an
      undersized complete rigid annuloplasty ring can abolish MR and is associated with
      improved functional status and left ventricular remodeling. It is unclear if
      surgery is associated with improved survival in this setting. There is a pressing
      need for well-conducted prospective randomized clinical trials to quantify the
      benefits of surgical repair of functional geometric MR.

PMID- 18325463
TI  - Atorvastatin attenuates cardiomyocyte loss in adult rats from protein-restricted
      dams.
AB  - BACKGROUND: Statins are cholesterol-lowering drugs that have been proved to
      prevent cardiac events. Their direct effects on cardiac remodeling, when
      administered in programmed protein restricted animals, still are unknown. METHODS
      AND RESULTS: Wistar male 6-month-old offspring from dams fed normal protein (NP,
      19% of protein) or low-protein (LP, 5% of protein) during pregnancy and first 10
      days after birth were studied. After weaning, male pups were allocated to
      untreated or treated groups with atorvastatin (low and high doses, 5 or 30
      mg.kg.day) in two different periods (from 21 days old to 3 months old and from 3
      to 6 months old). The blood pressure (BP) was 30% greater in untreated LP
      offspring than in treated offspring (from 165 +/- 6 mm Hg to 127 +/- 3 mm Hg, P <
      .01). After 1 month of treatment, only untreated LP offspring continued with high
      BP. Compared with untreated LP offspring, atorvastatin reduced blood glucose
      (less 30%, P < .05) and cardiomyocyte size (less 24%, P < .05), whereas untreated
      LP offspring had greater interstitial fibrosis (plus 74%, P < .01), reduction of
      myocardial vascularization (less 25%, P < .01) and major reduction of
      cardiomyocyte number (less 38%, P < .01) than treated LP offspring. CONCLUSION:
      Atorvastatin from 3 to 6 months olds in both low and high doses (but not from 0
      to 3 months) has beneficial effects improving myocardial vascularization by
      diminishing fibrosis and cardiomyocyte loss.

PMID- 18325464
TI  - In vivo effects of myocardial creatine depletion on left ventricular function
      morphology and lipid metabolism: study in a mouse model.
AB  - BACKGROUND: The failing heart is characterized by disturbed myocardial energy
      metabolism and creatine depletion. The aims of this study were to evaluate in
      vivo the effects of creatine (Cr) depletion on 1) left ventricular (LV) function,
      morphology, and lipid metabolism and 2) to test whether functional, morphologic,
      and metabolic disturbances induced by Cr depletion are reversible. METHODS AND
      RESULTS: Male Balb/c mice approximately 20 g were used. Two groups were studied:
      the mice treated with creatine analogue beta-guanidinopropionic acid (BGP) (n =
      30) and controls (n = 30). BGP (1 M) were administered by subcutaneously
      implanted osmotic minipumps for 4 weeks. The mice were examined in vivo using
      echocardiography. High-performance liquid chromatography was used for
      measurements of the myocardial creatine, adenosine nucleotides, and lipids. BGP
      was discontinued in a subgroup of mice and these animals were followed for an
      additional 4 weeks, after which echocardiography was performed under resting and
      stress conditions. Body weight was lower in BGP mice (P < .001) compared with the
      controls after 4 weeks. The total myocardial Cr pool was approximately 40% lower
      (P < .001), whereas total nucleotide pool (TAN) was 18% lower (P = n.s.) in the
      BGP group. LV systolic function was disturbed at rest and stress in the BGP mice
      (both P < .05). LV dimensions and LV mass were increased in the BGP group (P <
      .05). There was an accumulation of intracellular triglycerides in the BGP-treated
      mice (P < .05). Four weeks after BGP discontinuation Cr, TAN and TG content were
      restored to the normal levels while LV function, dimension, and mass were
      normalized. CONCLUSIONS: Myocardial Cr depletion results in LV dysfunction,
      pathologic remodeling, and lipid accumulation. These alterations are completely
      reversible on normalization of Cr content. Cr metabolism may be an important
      target for pharmacologic intervention to increase myocardial efficiency and
      structural integrity of the failing heart.

PMID- 18325465
TI  - Effect of low thyroid function on cardiac structure and function in spontaneously
      hypertensive heart failure rats.
AB  - BACKGROUND: Although low thyroid function is known to have detrimental effects on
      the cardiovascular system, including microvascular impairment, little is known
      about the pathophysiologic consequences of hypothyroidism in the background of
      hypertension. METHODS AND RESULTS: Hypothyroidism was induced in female
      spontaneously hypertensive heart failure (SHHF) rats by treatment with
      propylthiouracil (PTU) for 6 months. Untreated SHHF and normotensive Wistar Furth
      (WF) rats served as controls. In terminal experiments, heart weight,
      echocardiographic measurements, hemodynamics, and arteriolar morphometry were
      performed. Left ventricular internal diameter in systole and diastole were
      increased and wall thickness, ejection fraction, heart rate, systolic blood
      pressure, and +/-dP/dt were significantly decreased in the treatment group.
      Surprisingly, there were no observed differences in arteriolar density among the
      3 groups. CONCLUSIONS: As expected, PTU treatment of SHHF rats led to systolic
      dysfunction and chamber dilation. However, PTU treatment did not lead to
      arteriolar loss as previously observed in normotensive rats treated with PTU.
      These finding suggest that induced hypothyroidism leads to detrimental changes in
      SHHF rats, but the overall effects were no worse than those previously observed
      in normotensive rats treated with PTU.

PMID- 18325466
TI  - Endomyocardial upregulation of beta1 adrenoreceptor gene expression and
      myocardial contractile reserve following cardiac resynchronization therapy.
AB  - BACKGROUND: Congestive heart failure (CHF) is associated with a blunted force
      frequency relation (FFR) and myocardial contractile reserve (MCR) partially from
      a downregulation of beta1-adrenoreceptors (beta1-AR). We investigated whether
      acute and chronic cardiac resynchronization therapy (CRT) was capable of
      reversing the blunted FFR and MCR and if this was associated with upregulation of
      beta1-AR. METHODS AND RESULTS: Left ventricle dP/dtmax was invasively measured in
      10 CHF patients (New York Heart Association class > or =3; ejection fraction
      <25%) during incremental dual chamber (DDD)-CRT pacing at 70, 90, 110, and 130
      beats/min, with and without continuous infusion of intravenous dobutamine,
      immediately after CRT implantation (BL) and 4 months later (FU). In a subgroup of
      5 patients, serial left ventricle beta1 and beta2-AR gene expression was measured
      using reverse transcriptase-polymerase chain reaction. Four months after the
      initiation of resynchronization therapy, DDD-CRT pacing results in a significant
      upward shift of the heart rate versus LV dP/dtmax relationship (P < .01) with
      force frequency amplification as evidenced by the steeper slope of the force
      frequency response (P = .04). Infusion of dobutamine recruits myocardial
      contractile reserve and increases the heart rate versus LV dP/dtmax relationship
      at BL and at FU (both P < .05). However, only at follow-up was an additional
      force frequency amplification noticed (P < .05) during dobutamine infusion. This
      observation was paralleled by a significant upregulation of beta1-AR gene
      expression (P = .02). CONCLUSIONS: Chronic CRT is associated with a partial
      restoration of the FFR and with a recruitment in myocardial contractile reserve,
      which is paralleled by upregulation of beta1-AR.

PMID- 18325467
TI  - Immunohistochemical detection of the X-linked inhibitor of apoptosis protein
      (XIAP) in cervical squamous intraepithelial neoplasia and squamous carcinoma.
AB  - Premalignant and invasive squamous lesions of the uterine cervix were surveyed
      for the immunohistochemical detectability of the X-linked inhibitor of apoptosis
      protein (XIAP), believed to be the most potent of a novel group of proteins
      designated inhibitor of apoptosis proteins (IAPs). IAPs bind and prevent the
      activation of apoptosis-mediating caspases. Recent cancer biologic studies have
      implicated IAPs in therapeutic resistance and tumor aggressiveness. XIAP in
      particular is considered a highly promising target for drug discovery. Forty-four
      formalin-fixed and paraffin-embedded archival tissue sections were
      deparaffinized; subjected to citrate-based antigen retrieval; and immunostained
      with anti-XIAP monoclonal antibody (clone 48, BD Biosciences, San Jose, Calif)
      diluted 1:250, 4 degrees C x 72 hours; and developed using EnVision-Plus (Dako,
      Carpinteria, Calif) and diaminobenzidine as chromagen. Particulate or
      heterogeneous cytoplasmic staining was considered positive. Normal squamous
      epithelium was XIAP-positive in 7 of 34 cases (20.6%). Preinvasive
      intraepithelial lesions were positively stained in 54.5% of cases. Nineteen of 22
      invasive squamous carcinomas were positive (86.4%). The intensity and
      extensiveness of XIAP immunostaining varied among individual cases, but trended
      upward with loss of tumor differentiation: 8 of 9 cases with strong staining were
      poorly differentiated carcinomas. The present study suggests the characteristic
      link between poor tumor differentiation and more aggressive clinical behavior
      could in some malignancies be based upon the concomitant induction of XIAP.
      Induction of XIAP appears to occur in a subset of intraepithelial lesions; in
      others, XIAP is detected only upon progression to invasive carcinoma. Detection
      of enhanced XIAP expression may also pinpoint those lesions that might benefit
      from pharmacologic disruption of XIAP's actions.

PMID- 18325468
TI  - Clinicomorphologic features of a series of 10 cases of malignant triton tumors
      diagnosed over 10 years at a tertiary cancer hospital in Mumbai, India.
AB  - A rhabdomyoblastic differentiation in a malignant peripheral nerve sheath tumor
      is unusual and is termed as a malignant triton tumor. A series of 10 such cases
      with their clinicomorphological features, diagnosed over a 10-year period, is
      presented. The average age of occurrence was 30 years, with the maximum number of
      cases in the second decade and with male outnumbering female patients. More cases
      were seen in the setting of neurofibromatosis. On histology, 80% of the cases
      were of high grade. Distinct rhabdomyoblastic cells were identified in the areas
      of malignant peripheral nerve sheath tumor. Immunohistochemistry confirmed the
      neurogenic differentiation with varying S-100 expression and the rhabdomyoblastic
      differentiation with desmin and myoglobin positivity in all cases. Surgery with
      adequate margins constituted the treatment mainstay with adjuvant chemotherapy
      and/or radiotherapy in individual cases. On follow-up with 7 cases, 3 showed
      local recurrences, including one that, in addition to another 2 cases, showed
      lung metastasis. One patient died of the disease. This case along with another
      high-grade case displayed a diffuse Ki-67 and p53 positivity. Malignant triton
      tumor is an uncommon tumor associated with an aggressive behavior. Surgery with
      clear margins is the treatment mainstay. Adjuvant radiotherapy is effective.

PMID- 18325469
TI  - Applying morphologic techniques to evaluate hotdogs: what is in the hotdogs we
      eat?
AB  - Americans consume billions of hotdogs per year resulting in more than a billion
      dollars in retail sales. Package labels typically list some type of meat as the
      primary ingredient. The purpose of this study is to assess the meat and water
      content of several hotdog brands to determine if the package labels are accurate.
      Eight brands of hotdogs were evaluated for water content by weight. A variety of
      routine techniques in surgical pathology including routine light microscopy with
      hematoxylin-eosin-stained sections, special staining, immunohistochemistry, and
      electron microscopy were used to assess for meat content and for other
      recognizable components. Package labels indicated that the top-listed ingredient
      in all 8 brands was meat; the second listed ingredient was water (n = 6) and
      another type of meat (n = 2). Water comprised 44% to 69% (median, 57%) of the
      total weight. Meat content determined by microscopic cross-section analysis
      ranged from 2.9% to 21.2% (median, 5.7%). The cost per hotdog ($0.12-$0.42)
      roughly correlated with meat content. A variety of tissues were observed besides
      skeletal muscle including bone (n = 8), collagen (n = 8), blood vessels (n = 8),
      plant material (n = 8), peripheral nerve (n = 7), adipose (n = 5), cartilage (n =
      4), and skin (n = 1). Glial fibrillary acidic protein immunostaining was not
      observed in any of the hotdogs. Lipid content on oil red O staining was graded as
      moderate in 3 hotdogs and marked in 5 hotdogs. Electron microscopy showed
      recognizable skeletal muscle with evidence of degenerative changes. In
      conclusion, hotdog ingredient labels are misleading; most brands are more than
      50% water by weight. The amount of meat (skeletal muscle) in most brands
      comprised less than 10% of the cross-sectional surface area. More expensive
      brands generally had more meat. All hotdogs contained other tissue types (bone
      and cartilage) not related to skeletal muscle; brain tissue was not present.

PMID- 18325470
TI  - Utility of thin-layer preparations in the endometrial cytology: evaluation of
      benign endometrial lesions.
AB  - The purpose of the current study was to examine the use of thin-layer cytologic
      (TLC) preparation compared to conventional cytologic preparation (CCP) in the
      normal endometrium (proliferative, secretory, atrophic) and endometrial glandular
      and stromal breakdown (EGBD). During a 6-month period, we compiled 158 cases by
      collecting a direct endometrial sample using the Uterobrush. The material
      comprised 40 cases of proliferative endometrium, 42 cases of secretory
      endometrium, 46 cases of atrophic endometrium, and 30 cases of EGBD. The
      following points were investigated: (1) number of endometrial epithelial cell
      clumps; (2) presence of TLC > CCP cases on number of epithelial cell clumps; (3)
      number of condensed cluster of stromal cells; (4) presence of TLC > CCP cases on
      number of condensed cluster of stromal cells; (5) presence of metaplastic clumps
      with irregular protrusion-containing condensed stromal cluster; (6) presence of a
      clear background; (7) presence of blood vessel in TLC; (8) presence of blood
      vessel of length more than diameter of a field in object x20 glasses in TLC. (1)
      In all phases, the number of epithelial cell clumps per a unit area of a
      preparation of TLC is greater than in CCP. (2) Cells (condensed cluster of
      stromal cells and metaplastic clumps with irregular protrusion-containing
      condensed stromal cluster) of useful and adequate numbers for a diagnosis of EGBD
      were observed in TLC. (3) In all phases, TLC was significantly higher than CCP on
      the appearance of a clear background. (4) The proliferative endometrium and
      secretory endometrium were highly significant in comparison with atrophic
      endometrium and EGBD, respectively, in terms of the occurrence of a blood vessel
      of length more than diameter of a field in object x20 glasses. Although the
      preparation area of TLC is smaller than that of CCP, the preparation has a clean
      background so that an accurate report on the patient's condition is possible.
      Therefore, TLC preparation is a useful tool for the accurate and reliable
      diagnosis of normal endometrial phase and EGBD, because the preparation area is
      confined and identification of the target cell clumps is easy.

PMID- 18325471
TI  - Lymphovascular space invasion does not predict vaginal relapses in stage I
      endometrioid adenocarcinoma of the endometrium.
AB  - This study was conducted to determine whether, in a pure population of patients
      with International Federation of Gynecology and Obstetrics stage I endometrioid
      endometrial (S1EE) carcinoma that is confined to the uterus and without lymph
      node metastases, the presence of lymphovascular space invasion (LVSI) is
      positively associated with vaginal relapses. Pathologic reports for all S1EE
      diagnosed in a hysterectomy specimen during a 9-year period (1997-2005) were
      reviewed. Cases with LVSI were selected and immunohistochemical staining for
      CD34, factor VIII-related antigen and pancytokeratin were performed on the
      relevant slides for confirmation. Various established prognostic/predictive
      clinicopathologic parameters were documented for the whole cohort and were
      correlated with the presence or absence of LVSI. One-way analysis of variance
      with Bonferroni correction and Fisher exact/chi(2) tests were used in the
      respective comparisons of continuous and categoric variables among the different
      groups. A total of 345 patients were diagnosed with S1EE during this period. The
      mean patient age for the cohort was 61.9 (+/-12.2) years (range, 28-89 years) and
      median follow-up was 80 months. Among these 345 patients, LVSI was present in 52
      (15%), representing 1 (0.8%) of 121 stage 1A, 23 (14.5%) of 159 stage 1B, and 28
      (43%) of 65 stage 1C cases (P < .001). Pelvic and/or para-aortic lymph node
      dissection was performed in 216 cases, and none had positive lymph nodes. We
      noted that LVSI correlated significantly with nuclear grade, with LVSI being
      present in 48% (10/21), 18% (32/175), and 5% (7/140) of cases with nuclear grades
      3, 2, and 1 cases, respectively (P < .001). It was also more likely to be present
      in cases with architectural grades 2 and 3 (35/105) than grade 1 (16/234) (P <
      .01). Vaginal recurrences occurred in 2 (3.8%) of 52 patients with LVSI and 8
      (2.7%) of 293 patients without LVSI (P = .65). In addition, on univariate
      analysis, LVSI did not correlate significantly with patient age, body mass index
      (using 50-year and 30 body mass index thresholds, respectively), or diabetic
      status. We conclude that LVSI is seen in approximately 15% of S1EE, and
      correlates with established prognostic parameters such as the level of myometrial
      invasion (substage), nuclear grade, and architectural grade. However, LVSI does
      not denote an increased likelihood of vaginal recurrences in S1EE. The presence
      of LVSI should not, in of itself, alter clinical staging, or trigger unnecessary
      therapeutic intervention.

PMID- 18325472
TI  - Pseudomediastinal fibrosis caused by massive lymphadenopathy in domestically
      acquired particulate lung disease.
AB  - In this report, we describe a case of domestically acquired particulate lung
      disease (DAPLD) or "hut lung" in a 59-year-old woman of Moroccan descent who
      emigrated to the Netherlands, having lived in an rural area for most her life.
      She presented with obstructive lung disease and with signs of mediastinal
      fibrosis which were shown to be caused by massive enlargement of mediastinal
      lymph nodes. To the best of our knowledge, this is the first case of DAPLD from
      Morocco and the first report of a case of DAPLD mimicking mediastinal fibrosis.

PMID- 18325473
TI  - Salaries in histology.
AB  - An analysis of histology salaries from the last 4 national surveys conducted by
      the American Society of Clinical Pathologists is presented. The regional
      variations within and between years for histology salaries presented in the last
      4 national surveys of medical laboratory specialties are not statistically
      significant. Local variations greater than the national variations reflect the
      preponderant effect of local supply and demand over regional characteristics.
      Salaries by hospitals are significantly different only between 2 size categories
      and the supervisors' salary. There is no correlation between the salary increase
      for any histology position in any one year and the vacancy level in the previous
      year. On the other hand, the correlation between histotechnicians' salaries and
      both the cost of living and the median income are significant, as well as between
      the latter and the supervisors' salary. The histotechnologists' salaries are
      significantly correlated with the consumer price index but not with the inflation
      rate. A survey of histology salaries in foreign countries was also undertaken and
      compared with salaries in the United States. National salaries rank close to the
      general average for 10 foreign countries when expressed as ratios with the
      personal gross domestic product or with the countries' minimum wage. For the
      midpoint salary ranges, the United States ranks fourth after Canada, the United
      Kingdom, and Australia, the latter 3 countries with structured pay rates adjusted
      to local costs of living in contrast with United States' salary characteristics.
      Histology salaries rest on negotiations within each employer's salary structure
      and fluctuate according to license level, documented studies, special
      training(s), years of experience, references, and the ability to negotiate, where
      each side tries to take advantage of the other. The result is a heterogeneous and
      chaotic salary situation driven by personal and local needs, where the histology
      worker usually ends underpaid, especially in nonmedical settings.

PMID- 18325474
TI  - Endometrial stromal sarcoma of the small bowel.
AB  - Endometrial stromal sarcoma (ESS) is a rare mesenchymal neoplasm of the uterus,
      which is predominantly composed of endometrial stromal cells. When this feature
      is encountered in the extragenital area, the diagnosis is sometimes difficult
      especially if endometriosis is not present. We report a case of ESS arising in
      the small bowel without associated endometriosis in a 75-year-old woman and
      review the literatures for 16 cases of extrauterine extraovarian ESS. The most
      common site of the extrauterine extraovarian ESS is the gastrointestinal tract
      (8/16 cases). It is intimately associated with endometriosis (12/16 cases) as the
      case of ovarian ESS. Most ESSs were immunoreactive for CD10 (5/5 cases),
      progesterone receptor (10/10 cases), and estrogen receptor (9/11 cases), and
      negative for CD34 (0/7 cases). It may have a higher tendency for dissemination
      beyond its site of origin (12/16 cases) than its uterine counterpart. In
      conclusion, a careful morphological examination combined with immunohistochemical
      studies and consideration of ESS in the differential diagnosis would help in
      obtaining an accurate diagnosis in these rare circumstances.

PMID- 18325475
TI  - Primary synovial sarcoma of the kidney: corroboration with in situ polymerase
      chain reaction.
AB  - Synovial sarcoma is a tumor of the soft tissues with a unique chromosomal
      translocation t(X;18)(p 11.2;q11.2) that can be detected by polymerase chain
      reaction in tissue homogenates. The case of a 32-year-old woman with a primary
      synovial sarcoma of the kidney is described, the diagnosis was corroborated by
      the recently developed method of in situ polymerase chain reaction (IS-PCR).
      Synovial sarcoma of the kidney may be confused with other spindle cell tumors,
      for that reason IS-PCR may be useful to confirm the diagnosis in paraffin
      embedded material.

PMID- 18325476
TI  - Calcifying fibrous tumor of small intestine.
AB  - Calcifying fibrous tumor (CFT) is a rare benign tumor with a predilection for
      children and young adults that usually arises in the subcutaneous and deep soft
      tissues, pleura, or peritoneum. It presents histologically as a well
      circumscribed mass consisting of hyalinized, hypocellular lamellar collagen,
      bland spindle cells, chronic inflammatory cell infiltrates, and psammomatous or
      dystrophic calcifications. Calcifying fibrous tumor of the gastrointestinal tract
      is exceedingly rare and therefore prone to confusion with other spindle cell
      lesions more commonly encountered in this location. We describe 4 cases of
      calcifying fibrous tumor arising in the terminal ileum, one of which caused the
      heretofore unreported complication of intestinal intussusception, and discuss the
      differential diagnosis with other common and uncommon spindle cell lesions.

PMID- 18325477
TI  - Sarcomatoid carcinoma after radiation treatment of prostatic adenocarcinoma.
AB  - We report 2 patients with conventional prostatic adenocarcinoma who developed
      sarcomatoid carcinoma of probable prostatic origin 6 and 2.5 years after
      radiation treatment (seed implantation and external beam). Our cases had
      histologic features consistent with those cases previously reported in the
      literature. The tumors consisted of spindle cells with large hyperchromatic
      nuclei and a pattern mimicking a sarcoma. Immunohistochemical studies showed the
      tumors to be weakly positive for EMA, CK7, and vimentin. Ki67 staining showed
      positivity in more than 50% of tumor cells. The tumors also stained diffusely
      positive for p53 and p63. PSA and PAP were negative. Clinically, the sarcomatoid
      carcinomas appeared to be of prostatic origin. The pathogenesis of the tumors is
      still uncertain but most likely represent a radiation-induced dedifferentiation
      of prostatic adenocarcinoma.

PMID- 18325478
TI  - Signet ring cell gastric schwannoma: report of a new distinctive morphological
      variant.
AB  - An 89-year-old woman was seen for indigestion, light chest pain, and melanotic
      stools. Endoscopic examination revealed 2 submucosal gastric masses. A subtotal
      gastrectomy showed 2 submucosal masses in the stomach: one infiltrating through
      the muscularis propria into the serosa, the second one, a well-circumscribed
      submucosal nodule. Histologic examination showed large tumor cells infiltrating
      diffusely through the muscularis propria into the subserosa. On higher
      magnification, numerous signet ring cells were present against a myxoid stroma,
      in addition to large vacuolated epithelioid cells. There was no evidence of
      invasion, necrosis, nuclear pleomorphism, or mitotic activity. Initial diagnostic
      considerations based on the histology included signet ring cell carcinoma,
      malignant melanoma, and a myxoid mesenchymal tumor, including gastrointestinal
      stromal tumor. A panel of immunohistochemical stains showed diffuse strong
      positivity for S-100 protein and negative reaction for CD117, bcl-2, cytokeratin
      AE1/AE3, Melan-A, HMB45, smooth muscle antigen, and other differentiation
      markers. Electron microscopic examination revealed elongated, complex, and
      interdigitating cell processes covered by a thin layer of continuous basement
      membrane material characteristic of peripheral nerve sheath differentiation. The
      presentation of this tumor was significant in that it was multifocal and
      infiltrative, mimicking a malignant neoplasm. The extensive myxoid/signet ring
      cell change represents a heretofore-unreported histologic variant of gastric
      schwannoma.

PMID- 18325479
TI  - Current overview of the role of Akt in cancer studies via applied
      immunohistochemistry.
AB  - The family of AKT kinases, AKT-1, 2, and 3, collectively play a crucial role in
      key processes, as well as pathologic processes such as oncogenesis. The numerous
      AKT phosphorylation targets include proteins essential to the regulation of cell
      cycling, protein translation, suppression of programmed cell death, all of which,
      upon activation via AKT-mediated phosphorylation, promote tumor growth, survival,
      and aggressiveness. Activation of the AKT pathway can be immunohistochemically
      detected with antibodies that specifically react with phosphorylated or
      nonphosphorylated forms of AKT. The following review summarizes the use of
      phospho-AKT immunohistochemistry as a potentially valuable tool in cancer
      prognostication in a wide spectrum of common and uncommon malignancies, including
      squamous carcinoma of cervix and of head and neck; adenocarcinoma of endometrium,
      ovarian, breast, prostate, kidney, colon, and pancreas; carcinomas of lung and
      thyroid; and hematopoietic, soft tissue, and central nervous system neoplasms. To
      date, the findings overall suggest that the major use of p-AKT
      immunohistochemical staining lies in prognostication and possibly in
      individualization of therapy rather than in differential diagnosis.

PMID- 18325480
TI  - Dominance of Giardia assemblage B in Leon, Nicaragua.
AB  - Giardiasis is a major problem in Leon, Nicaragua, yet despite this no data are
      available regarding the prevalence of different Giardia genotypes in this area.
      To address this question, a molecular analysis of Giardia isolates from humans
      and dogs living in the same area in Leon, Nicaragua was performed. Giardia
      isolates from 119 Nicaraguan patients and 8 dogs were successfully genotyped
      using single and/or nested beta-giardin PCR with subsequent restriction length
      fragment polymorphism (RFLP) analysis. The analyses of human samples yielded 94
      (79%) assemblage B isolates and 25 (21%) assemblage A isolates. Only the non
      human-associated assemblages C and D were found in the dog samples. Sixteen
      isolates with assemblage A pattern, 26 isolates with assemblage B pattern and all
      dog isolates were further characterized by sequencing the nested beta-giardin PCR
      product and by molecular analyses of the glutamate dehydrogenase (gdh) gene.
      Within the study area the assemblage A isolates were highly genetically
      homogenous, showing only sub-genotypes A2 (n=3) or A3 (n=13) at the beta-giardin
      locus and AII only at the gdh locus while assemblage B showed a high genetic
      polymorphism at both loci. Seven different sub-genotypes were identified within
      13 of the sequenced assemblage B beta-giardin isolates. The remaining 13
      sequenced assemblage B-isolates appeared to contain several different variants of
      the beta-giardin gene since the chromatograms displayed one to seven double
      peaks. The gdh sequences showed an even higher polymorphism since only 2 of 26
      assemblage B isolates were without double peaks. Two mixed infections between
      assemblage A and B were found when the gdh gene was analyzed. Polymorphisms were
      also observed in the dog-associated assemblages C and D, but to a lesser extent
      than in assemblage B.

PMID- 18325481
TI  - Human periodontal fibroblast response to a nanostructured hydroxyapatite bone
      replacement graft in vitro.
AB  - OBJECTIVE: The efficacy of nanostructured hydroxyapatite (NHA) for the treatment
      of osseous defects has been demonstrated in recent studies, even though the
      underlining biological mechanism is still poorly known. This study examined the
      alterations in cellular adhesion and mitogenic responses in human periodontal
      ligament (PDL) cells treated with a novel nanostructured hydroxyapatite bone
      graft substitute and characterized associated changes in cellular signalling
      pathways. METHODS: Cultured PDL cells were stimulated with NHA in a surface
      coated form. Proliferation was determined by bromodeoxyuridine (BrdU)
      incorporation and cell adhesion was analysed by a colorimetric assay. In order to
      understand altered adhesion properties of PDL fibroblasts their integrin profile
      was analysed and the phosphorylation status of focal adhesion kinase (FAK) and
      beta1 integrin was determined by immunoblotting. In order to understand the
      signalling mechanisms of increased cell proliferation of PDL cells caused by NHA,
      the phosphorylation status of the serine/threonine protein kinase Akt, of the
      signal regulated kinases ERK1/2 and of the epidermal growth factor receptor
      (EGFR) was analysed by western blot using phospho-specific antibodies. RESULTS:
      The results indicated that NHA is a strong stimulator of PDL cell attachment and
      proliferation. Mechanistically, alpha5beta1 integrin-mediated cellular adhesion
      of PDL fibroblasts, which resulted in altered phosphorylation and activation
      levels of FAK. Proliferation mediated by NHA was mechanistically caused by
      activation of the epidermal growth factor receptor (EGFR) pathway and its
      downstream targets ERK1/2 and Akt. CONCLUSIONS: In sum, our findings present
      evidence that alpha5beta1 integrin-mediated cellular adhesion of NHA to PDL
      fibroblasts, whereas proliferation was caused by activation of the epidermal
      growth factor receptor (EGFR) and the MAP kinase (ERK1/2) and Akt pathways.

PMID- 18325482
TI  - The interaction of state and trait aspects of self-focused attention affects
      genital, but not subjective, sexual arousal in sexually functional women.
AB  - In this study we investigated the effects of state and trait aspects of self
      focused attention on genital and subjective sexual arousal of sexually
      functional, healthy women during presentation of audiovisual erotic stimuli.
      Psychophysiological sexual response was measured as vaginal pulse amplitude using
      a vaginal photoplethysmograph. Experiential aspects of sexual arousal were
      measured both during stimulus presentation and retrospectively after stimulus
      offset. Trait level of sexual self-focus was measured with the Sexual Self
      Consciousness Scale. State self-focus was induced by switching on a TV camera
      that pointed at the participant's face and upper torso. A manipulation check
      revealed that both groups experienced equally elevated levels of self-focused
      attention of their physical appearance. Induction of state self-focus per se did
      not affect genital responses, but an interaction effect of self-focus and
      participants' level of trait sexual self-focus was revealed. Compared with women
      with low scores on this trait, women with high scores exhibited smaller genital
      responses when state self-focus was induced. Both groups did not differ when no
      self-focus was induced. Increase of state self-focus did not affect subjective
      sexual arousal, but participants with a high level of trait sexual self-focus
      reported stronger subjective arousal, compared with those with low trait level.
      The results were discussed with reference to previous work in this field. Some
      implications for treatment of sexual arousal disorder were discussed.

PMID- 18325483
TI  - The dopamine D(3) receptor Ser9Gly polymorphism modulates prepulse inhibition of
      the acoustic startle reflex.
AB  - BACKGROUND: The dopamine D(3) receptor (DRD(3)) is suspected to modulate prepulse
      inhibition (PPI) in animals and humans, but definite conclusions cannot be drawn
      due to lack of selective DRD(3) ligands. The Ser9Gly polymorphism is a common
      variant of the DRD(3) gene and determines the gain of function of the D(3)
      receptor. This is the first study to examine the influence of the DRD(3) Ser9Gly
      polymorphism on human PPI. METHODS: Prepulse inhibition was measured in 101
      healthy male subjects presented with 75-dB and 85-dB prepulses at 30-, 60-, and
      120-msec prepulse-pulse intervals. Subjects were grouped according to their
      DRD(3) status into a Gly/Gly, a Ser/Gly, and a Ser/Ser group. RESULTS: Analyses
      of variance showed that at all prepulse and interval conditions, Gly/Gly
      individuals had the lowest PPI and the greatest onset latency facilitation and
      Ser/Ser individuals had the highest PPI and the lowest onset latency
      facilitation, while Ser/Gly individuals were intermediate. CONCLUSIONS: These
      results suggest that PPI is modulated by the D(3) receptor and its levels depend
      on the Ser9Gly polymorphism.

PMID- 18325484
TI  - Role of glycine receptors and glycine release for the neuroprotective activity of
      bilobalide.
AB  - Bilobalide, a constituent of Ginkgo biloba, has neuroprotective properties. Its
      mechanism of action is unknown but it was recently found to interact with
      neuronal transmission mediated by glutamate, gamma-aminobutyric acid (GABA) and
      glycine. The goal of this study was to test the interaction of bilobalide with
      glycine in assays of neuroprotection. In rat hippocampal slices exposed to N
      methyl-D-aspartate (NMDA), release of choline indicates breakdown of membrane
      phospholipids. NMDA-induced choline release was almost completely blocked in the
      presence of bilobalide (10 microM). Glycine (10-100 microM) antagonized the
      inhibitory action of bilobalide in this assay. In a second assay of
      excitotoxicity, we measured tissue water content as an indicator of cytotoxic
      edema formation in hippocampal slices which were exposed to NMDA. In this assay,
      edema formation was suppressed by bilobalide but bilobalide's action was
      attenuated in the presence of glycine and of D-serine (100 microM each). To
      investigate bilobalide's interaction with glycine receptors directly, we
      determined 36chloride flux in rat cortico-hippocampal synaptoneurosomes. Glycine
      (100 microM) was inactive in this assay indicating an absence of functional
      glycine-A receptors in this preparation. [3H]Glycine was used to assess binding
      at the glycine binding site of the NMDA receptor but bilobalide was found to be
      inactive in this assay. Finally, [3H]glycine release was monitored in hippocampal
      slices exposed to oxygen-glucose deprivation. In this model, glycine release was
      induced by ischemia, an effect that was strongly reduced by bilobalide. We
      conclude that bilobalide does not interact with glycine receptors in
      neurochemical assays but it significantly reduces the release of glycine under
      ischemic conditions. This effect likely contributes to bilobalide's
      neuroprotective effects in assays of excitotoxicity and ischemia.

PMID- 18325485
TI  - Effects of an NMDA-receptor antagonist MK-801 on an MMN-like response recorded in
      anesthetized rats.
AB  - In the human brain, auditory sensory memory has been extensively studied using a
      well-defined component of event-related potential named the mismatch negativity
      (MMN). The MMN is generated in the auditory and frontal cortices in response to
      deviant stimuli. In monkeys, cortical N-methyl-d-aspartate (NMDA) receptors have
      a central role in the generation of the MMN. MMN-like responses have also been
      recorded in other animals, including rats. The present study aimed at determining
      whether the MMN-like response in rats depends on an intact NMDA-receptor system.
      We recorded auditory evoked responses during an oddball paradigm epidurally in
      anesthetized rats that had received intraperitoneal injections of saline or an
      NMDA-receptor antagonist MK-801. An MMN-like response was recorded in the oddball
      paradigm in saline-treated rats. Further, this response was dose-dependently
      blocked by MK-801. These results suggest that the MMN-like response in rats
      depends on an intact NMDA-receptor system.

PMID- 18325487
TI  - Nasturtium officinale reduces oxidative stress and enhances antioxidant capacity
      in hypercholesterolaemic rats.
AB  - Nasturtium officinale R. Br. (Brassicaceae) has been used as a home remedy by the
      people of south eastern (SE) region of Iran as a medicinal plant. This
      therapeutical application has been attributed to Nasturtium officinale (N.
      officinale) antioxidant capacity which is mostly tested by means of cell-free
      assays: 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant
      power (FRAP). In addition, the antioxidant effect of N. officinale extract has
      been investigated in hypercholesterolaemic rats in vivo. The results revealed
      that the extract has notable scavenging activity against DPPH radicals as well as
      potent reducing power in FRAP assay. Intragastric administration of N. officinale
      (500 mg/kg body weight per day) to groups of hypercholesterolaemic rats for 30
      days lowered their blood total cholesterol (TC), triglyceride (TG), and low
      density lipoprotein cholesterol (LDL-C) levels by 37, 44 and 48%, respectively.
      However, the blood high density lipoprotein cholesterol (HDL-C) levels in the
      same treated rats increased by 16%. To evaluate the mechanism(s) of action, we
      studied the antioxidative potential of N. officinale extract in terms of catalase
      (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione
      reductase (GR) activities and also the level of reduced glutathione (GSH) in the
      liver tissues. In addition, hepatic tissue malondialdehyde level (MDA, an index
      of lipid peroxidation) was also determined. Under hypercholesterolaemic
      condition, hepatic MDA was increased. Moreover, our data indicated GSH depletion
      along with significant reduction in the activities of CAT and SOD in rats fed
      high-fat diet rats. On the other hand, significant elevation in the activities of
      GPx and GR were seen in the same group of rats. Treatment of
      hypercholesterolaemic rats with N. officinale extract significantly increased the
      GSH level along with enhanced CAT and SOD activities in liver tissues.
      Furthermore, N. officinale extract significantly decreased hepatic MDA as well as
      GPx and GR activities in plant-treated rats. Based on our data, it can be
      concluded that N. officinale has a high hypolipidaemic activity and this may be
      attributed to its antioxidative potential.

PMID- 18325488
TI  - A bilateral integrative health-care knowledge service mechanism based on
      'MedGrid'.
AB  - Current health-care organizations are encountering impression of paucity of
      medical knowledge. This paper classifies medical knowledge with new scopes. The
      discovery of health-care 'knowledge flow' initiates a bilateral integrative
      health-care knowledge service, and we make medical knowledge 'flow' around and
      gain comprehensive effectiveness through six operations (such as knowledge
      refreshing...). Seizing the active demand of Chinese health-care revolution, this
      paper presents 'MedGrid', which is a platform with medical ontology and knowledge
      contents service. Each level and detailed contents are described on MedGrid info
      structure. Moreover, a new diagnosis and treatment mechanism are formed by
      technically connecting with electronic health-care records (EHRs).

PMID- 18325486
TI  - Regulation of IGF-I function by proinflammatory cytokines: at the interface of
      immunology and endocrinology.
AB  - During the past decade, the immune and endocrine systems have been discovered to
      interact in controlling physiologic processes as diverse as cell growth and
      differentiation, metabolism, and even human and animal behavior. The interaction
      between these two major physiological systems is a bi-directional process. While
      it has been well documented that hormones, including prolactin (PRL), growth
      hormone (GH), insulin-like growth factor-I (IGF-I), and thyroid-stimulating
      hormone (TSH), regulate a variety of immune events, a great deal of data have
      accumulated supporting the notion that cytokines from the innate immune system
      also affect the neuroendocrine system. Communication between these two systems
      coordinates processes that are necessary to maintain homeostasis. Proinflammatory
      cytokines often act as negative regulatory signals that temper the action of
      hormones and growth factors. This system of 'checks and balances' is an active,
      ongoing process, even in healthy individuals. Dysregulation of this process has
      been implicated as a potential pathogenic factor in the development of co-morbid
      conditions associated with several chronic inflammatory diseases, including type
      2 diabetes, cardiovascular disease, cerebrovascular disease, inflammatory bowel
      disease, rheumatoid arthritis, major depression, and even normal aging. Over the
      past decade, research in our laboratory has focused on the ability of the major
      proinflammatory cytokines, tumor necrosis factor (TNF)alpha and interleukin (IL)
      1beta, to induce a state of IGF resistance. This review will highlight these and
      other new findings by explaining how proinflammatory cytokines induce resistance
      to the major growth factor, insulin-like growth factor-I (IGF-I). We also
      highlight that IGF-I can induce resistance or reduce sensitivity to brain
      TNFalpha and discuss how TNFalpha, IL-1beta, and IGF-I interact to regulate
      several aspects of behavior and cognition.

PMID- 18325489
TI  - Integrated multimedia electronic patient record and graph-based image information
      for cerebral tumors.
AB  - Current electronic patient record (EPR) implementations do not incorporate
      medical images, nor structural information extracted from them, despite images
      increasing role for diagnosis. This paper presents an integration framework into
      EPRs of anatomical and pathological knowledge extracted from segmented magnetic
      resonance imaging (MRI), applying a graph of representation for anatomical and
      functional information for individual patients. Focusing on cerebral tumors
      examination and patient follow-up, multimedia EPRs were created and evaluated
      through a 3D navigation application, developed with open-source libraries and
      standards. Results suggest that the enhanced clinical information scheme could
      lead to original changes in the way medical experts utilize image-based
      information.

PMID- 18325490
TI  - Sox9 is required for prostate development.
AB  - The mammalian prostate arises from the urogenital sinus and few factors have been
      identified to be important in the early stages of prostate development. In this
      study we show that the transcription factor Sox9 is expressed in the epithelia of
      all mouse prostatic lobes from the initial stages of their development. We used a
      conditional approach with mice expressing Cre recombinase under the control of
      Nkx3.1 regulatory sequences to delete Sox9 from the developing prostate. Mice
      with a prostate specific deletion of Sox9 showed a lack of ventral prostate
      development and abnormal anterior prostate differentiation. Analysis of these
      mutant animals revealed an early loss of expression of genes specific to the
      prostate epithelia such as Nkx3.1 and Shh and a marked reduction in proliferation
      in the ventral prostate but not in other lobes. Fgf signalling, through the MAPK
      pathway, has been shown to be important in prostate development and a lobe
      specific phenotype was reported for a prostate specific Fgfr2 mutant mouse model.
      Here we show that the levels of Fgfr2 and Sprouty2, a downstream target of Fgf
      signalling, were severely reduced in the ventral prostate of Sox9 mutant animals
      but not in other lobes. Prostate organ culture studies with a Mek inhibitor,
      U0126, and a Fgf receptor inhibitor, SU5402, indicate that the timing of
      expression of Cre in the mutant animals could account for the lobe specific
      phenotype in the Sox9 and Fgfr2 mutants. These studies imply that Sox9 is
      required for the early differentiation of the prostate bud epithelia.

PMID- 18325491
TI  - Differential regulation of prostaglandin synthesis in neonatal rat microglia and
      astrocytes by somatostatin.
AB  - The aim of the present study was to investigate the role of somatostatin in the
      regulation of brain inflammation. We used lipopolysaccharide-induced
      prostaglandin E2 production in neonatal rat microglia and in astrocytes as a
      model of brain inflammation. Our data show an unexpected differential effect of
      somatostatin on lipopolysaccharide-induced prostaglandin E2 synthesis in rat
      microglia vs. in astrocytes. Somatostatin markedly inhibited the
      lipopolysaccharide-induced prostaglandin E2 synthesis in microglia whereas, on
      the contrary, in astrocytes the lipopolysaccharide-induced prostaglandin E2
      production was actually enhanced by somatostatin. These novel observations imply
      that somatostatin may regulate brain inflammation in a dual manner.

PMID- 18325492
TI  - Inhibiting wild-type and C299S mutant AKR1B10; a homologue of aldose reductase
      upregulated in cancers.
AB  - AKR1B10 is an aldose reductase (AR) homologue overexpressed in liver cancer and
      various forms of that enzyme in carcinomas catalyze the reduction of anticancer
      drugs, potential cytostatic drug, and dl-glyceraldehyde but do not catalyze the
      reduction of glucose. Kinetic parameters for wild-type and C299S mutant AKR1B10
      indicate that substitution of serine for cysteine at position 299 reduces the
      affinity of this protein for dl-glyceraldehyde and enhances its catalytic
      activity. Fibrates suppress peroxisome proliferation and the development of liver
      cancer in human. Here we report the potency of fibrate-mediated inhibition of the
      carbonyl reduction catalyzed by wild-type and C299S mutant AKR1B10 and compare it
      with known AR inhibitors. Wild-type AKR1B10-catalyzed carbonyl reduction follows
      pure non-competitive inhibition kinetics using zopolrestat, EBPC or sorbinil,
      whereas fenofibrate, Wy 14,643, ciprofibrate and fenofibric acid follow mixed non
      competitive inhibition kinetics. In contrast, catalysis of reaction by the C299S
      AKR1B10 mutant is not inhibited by sorbinil and EBPC. Despite these differences,
      the C299S AKR1B10 mutant still manifests kinetics similar to the wild-type
      protein with other fibrates including zopolrestat, fenofibrate, Wy 14,346,
      gemfibrozil and ciprofibrate that show mixed non-competitive inhibition kinetics.
      The reaction of the mutant AKR1B10 is inhibited by fenofibric acid, but manifests
      pure non-competitive inhibition kinetics that are different from those
      demonstrated for the wild-type enzyme.

PMID- 18325493
TI  - Using pharmacokinetic-pharmacodynamic modelling as a tool for prediction of
      therapeutic effective plasma levels of antipsychotics.
AB  - In the rat, selective suppression of conditioned avoidance response has been
      widely reported as a test with high predictive validity for antipsychotic
      efficacy. Recent studies have shown that the relationship between dopamine D2
      receptor occupancy and the suppression of conditioned avoidance response
      behaviour correlates well with the relationship between human dopamine D2
      receptor occupancy and clinical effect. The aim of the present study was to
      evaluate how pharmacokinetic/pharmacodynamic (PK/PD) predictions of therapeutic
      effective steady-state plasma levels by means of conditioned avoidance response
      behaviour in rodents, correlate with clinically relevant plasma exposure for the
      classical antipsychotic drug haloperidol and four second generation
      antipsychotics: sertindole, clozapine, risperidone and olanzapine, including
      selected metabolites. In order to confirm the validity of the present conditioned
      avoidance response procedure, in vivo striatal dopamine D2 receptor occupancy was
      determined in parallel using 3H-raclopride as the radioligand. The PK/PD
      relationship was established by modelling the time-response and time-plasma
      concentration data. We found the order of dopamine D2 receptor occupancy required
      to suppress conditioned avoidance response behaviour according to EC50
      measurements to be sertindole (+dehydrosertindole)=dehydrosertindole=paliperidone
      (the metabolite of risperidone)=haloperidol=olanzapine>risperidone>>clozapine.
      Overall, a good agreement was observed between the rat dopamine D2 receptor
      occupancy levels providing 50% response in the conditioned avoidance response
      test and the dopamine D2 receptor occupancy levels reported from responding
      schizophrenic patients treated with antipsychotics. Predictions of
      therapeutically effective steady-state levels for sertindole (+dehydrosertindole)
      and olanzapine were 3-4-fold too high whereas for haloperidol, clozapine and
      risperidone the predicted steady-state EC50 in conditioned avoidance responding
      rats correlated well with the therapeutically effective plasma levels observed in
      patients. Accordingly, the proposed PK/PD model may act as a guide for
      determining effective plasma concentrations of potential antipsychotics in the
      clinical setting and thereby accelerating the overall drug development process.

PMID- 18325494
TI  - Cell specific differences between human adipose-derived and mesenchymal-stromal
      cells despite similar differentiation potentials.
AB  - Stromal cells from bone marrow and adipose tissue are attractive sources of adult
      progenitors for cell-based therapy. However, whether those cell populations
      represent intrinsically different cell types is still largely under debate. The
      aim of this study was to systematically and quantitatively compare adipose
      derived stromal cells (ADSC) and bone marrow-derived multipotent mesenchymal
      stromal cells (BM-MSC). The quantitative comparison was realized using Taqman Low
      Density Array, 2D electrophoresis and differentiation functional assays in vitro.
      Furthermore, cells engineered to express TGFbeta1 were injected into the intra
      articular space of mouse knee joints in order to determine whether they were able
      to form new differentiated tissues in vivo. Our data revealed cell specific
      differences at transcriptional and proteomic levels between both cell types
      according to their tissue origin as well as functional differences in their
      differentiation processes towards adipogenic, osteogenic and chondrogenic
      programs. Nevertheless, in vitro as well as in vivo ADSC displayed the same
      ability than MSC to differentiate towards chondrocytes/osteoblasts, comforting
      the status of both cell sources as promising regenerative cells. In summary, our
      observations indicate that ADSC and MSC are fundamentally different cell types
      and differently committed cells.

PMID- 18325495
TI  - Dependence of cAMP meditated increases in Cl- and HCO(3)- permeability on CFTR in
      bovine corneal endothelial cells.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is present on the
      apical membrane of corneal endothelial cells. Increasing intracellular [cAMP]
      with forskolin stimulates an NPPB and glibenclamide-inhibitable apical Cl(-) and
      HCO(3)(-) permeability [Sun, X.C., Bonanno, J.A., 2002. Expression, localization,
      and functional evaluation of CFTR in bovine corneal endothelial cells. Am. J.
      Physiol. Cell Physiol. 282, C673-C683]. To definitively determine that the
      increased permeability is dependent on CFTR, we used an siRNA knockdown approach.
      Apical Cl(-) and HCO(3)(-) permeability and steady-state HCO(3)(-) flux were
      measured in the presence or absence of forskolin using cultured bovine corneal
      endothelial cells that were transfected with CFTR siRNA or a scrambled sequence
      control. CFTR protein expression was reduced by approximately 80% in CFTR siRNA
      treated cultures. Forskolin (10 microM) increased apical chloride permeability by
      7-fold, which was reduced to control level in siRNA treated cells. CFTR siRNA
      treatment had no effect on baseline apical chloride permeability. Apical HCO(3)(
      ) permeability was increased 2-fold by 10 microM forskolin, which was reduced to
      control level in siRNA treated cultures. Similarly, there was no effect on
      baseline apical HCO(3)(-) permeability by knocking down CFTR expression. The
      steady-state apical-basolateral pH gradient (DeltapH) at 4h in control cultures
      was increased approximately 2.5-fold by forskolin. In CFTR siRNA treated cells,
      the baseline DeltapH was similar to control, however forskolin did not have a
      significant effect. We conclude that forskolin induced increases in apical
      HCO(3)(-) permeability in bovine corneal endothelium requires CFTR. However, CFTR
      does not have a major role in determining baseline apical chloride or HCO(3)(-)
      permeability.

PMID- 18325496
TI  - Comparison of the effects of Artemisia vulgaris and Artemisia absinthium growing
      in western Anatolia against trichinellosis (Trichinella spiralis) in rats.
AB  - Trichinellosis often causing diarrhea and more rarely fever, periorbital edema
      and myositis in human, is commonly treated with benzimidazole derivatives. The
      Artemisia genus has been found to be effective against a variety of parasites. In
      the present study, the efficacy against trichinellosis (Trichinella spiralis) of
      Artemisia vulgaris and Artemisia absinthium was examined for the first time in
      rats. The results of trichinoscopy and artificial digestion, during the enteral
      (adult) phase of the illness show that 300 mg/kg doses of methanol extracts of
      the aerial parts of A. vulgaris and A. absinthium reduced the larval rate by
      75.6% and 63.5% in tongue, 53.4% and 37.7% in diaphragm, 67.8% and 46.2% in
      quadriceps, and 66.7% and 60.5% in biceps-triceps muscles of rats, respectively.
      Furthermore, during the parenteral (encapsulated larvae) phase, 600 mg/kg doses
      of A. vulgaris and A. absinthium extracts decreased the larval rate by 66.4% and
      59.9% in tongue, 57.4% and 50.0% in diaphragm, 47.6% and 43.7% in quadriceps,
      60.2% and 46.4% in biceps-triceps muscles of rats, respectively. Analysis of
      antibody also showed that A. vulgaris significantly reduced the antibody response
      (P<0.05) during the enteral and parenteral phases. Thus, the results of the
      present study revealed that A. vulgaris could be an alternative drug against
      trichinellosis.

PMID- 18325497
TI  - Amphiregulin is much more abundantly expressed than transforming growth factor
      alpha and epidermal growth factor in human follicular fluid obtained from
      patients undergoing in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To identify the most important epidermal growth factor (EGF) receptor
      ligand in the LH or hCG signal pathway in human ovary. DESIGN: A retrospective
      clinical study. SETTING: Tertiary university hospital. PATIENT(S): Ninety-eight
      infertile patients who underwent IVF-embryo transfer. INTERVENTION(S): Sera and
      follicular fluid were collected at the time of oocyte retrieval. The levels of
      EGF, transforming growth factor-alpha (TGFalpha), and amphiregulin (AR) were
      measured in follicular fluid and sera by using ELISA. MAIN OUTCOME MEASURE(S):
      The relationships between the level of AR and level of hCG, fertilization rate,
      and embryo quality. RESULT(S): Amphiregulin was abundantly expressed in
      follicular fluid after hCG stimulation. Although large differences were found
      between AR and both EGF and TGFalpha in follicular fluid, no significant
      difference was detected in the levels of the three EGF receptor ligands in sera.
      The level of AR was inversely correlated with the fertilization rate and hCG
      level, whereas little significant association was observed between the level of
      AR and embryo quality. CONCLUSION(S): Amphiregulin was expressed most dominantly
      among EGF receptor ligands tested and may mediate the hCG signal in human oocyte
      maturation. Elaborate interaction between AR and hCG may be required for an
      optimal oocyte maturation.

PMID- 18325499
TI  - Injection of embryo culture supernatant prior to blastocyst transfer--cofactor?

PMID- 18325501
TI  - Appropriate methods to monitor controlled ovarian hyperstimulation?

PMID- 18325502
TI  - Counting ovarian follicles is not without its challenges.

PMID- 18325504
TI  - Peer review and reflection continues forever.

PMID- 18325505
TI  - The utilization of assisted reproductive technology.

PMID- 18325506
TI  - Body mass index is an independent risk factor for the development of endometrial
      polyps in patients undergoing in vitro fertilization.
AB  - OBJECTIVE: To determine the subgroup of patients in whom office hysteroscopy
      should be routinely performed before an in vitro fertilization (IVF) program.
      DESIGN: Retrospective cohort analysis. SETTING: Tertiary education and research
      hospital. PATIENT(S): Two hundred twenty-three patients who underwent a uterine
      evaluation by office hysteroscopy before the IVF and embryo transfer cycle.
      INTERVENTION(S): The office hysteroscopy was performed in the follicular phase of
      the menstrual cycle before the IVF cycle. MAIN OUTCOME MEASURE(S): The office
      findings: number of polyps, number of multiple polyps, and polyp size. RESULT(S):
      Patients with polycystic ovary syndrome (PCOS) had a higher number of endometrial
      polyps, but the difference was not statistically significant (28.9% vs. 18.3%).
      When comparing the patients according to BMI, patients with BMI >or=30 had a
      statistically significantly higher number of endometrial polyps versus BMI <30
      (52% vs. 15%). On the other hand, obesity was positively correlated with the
      occurrence of polyps, size of the polyps, and occurrence of multiple number of
      polyps in the correlation analysis. In addition, logistic regression analysis
      using age, obesity, duration of infertility, and estradiol levels revealed that
      obesity was an independent prognostic factor for the development of endometrial
      polyps. CONCLUSION(S): Office hysteroscopy should be performed in patients with
      BMI >or=30 because obesity may act as an initiator for the pathogenesis of
      endometrial polyps.

PMID- 18325507
TI  - Always important--statistical justification for pooling heterogeneous studies?

PMID- 18325508
TI  - Inappropriate gonadotropin secretion in polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate inappropriate gonadotropin secretion in women with
      polycystic ovary syndrome (PCOS). DESIGN: Retrospective study. SETTING: Academic
      tertiary center. PATIENT(S): A total of 373 women were classified into three
      groups: [1] healthy control women (n = 48); [2] women who were positive for PCOS
      risk factor; and [3] women with PCOS (n = 251). INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Gonadotropin levels, LH-FSH ratio, body mass index, and
      clinical and/or biochemical presentations of PCOS. RESULT(S): The area under the
      receiver operating characteristic curve, used to predict PCOS for the LH-FSH
      ratio, showed similar diagnostic performance to total T and average ovarian
      volume. The LH-FSH ratio exhibits greater observed accuracy than total T and
      average ovarian volume for evaluation of women with oligomenorrhea or
      anovulation. An LH-FSH ratio of >1 presented the best combination of sensitivity
      and specificity. Body mass index was positively correlated with total T in non
      PCOS and PCOS groups; however, body mass index was negatively correlated with LH
      in PCOS but showed no correlation in non-PCOS subjects. CONCLUSION(S): The LH-FSH
      ratio is a valuable diagnostic tool in evaluating women with PCOS and
      oligomenorrhea or anovulation, and an LH-FSH ratio of >1 may be used as a
      decision threshold. The link between body mass index and LH may provide clues for
      further understanding the pathological milieu of PCOS.

PMID- 18325509
TI  - Sildenafil citrate (Viagra) impairs fertilization and early embryo development in
      mice.
AB  - OBJECTIVE: To determine the effects of sildenafil citrate, a cyclic monophosphate
      specific type 5 phosphodiesterase inhibitor known to affect sperm function, on
      fertilization and early embryo cleavage. DESIGN: This acute mammal study included
      male and female mice assigned randomly, the females sacrificed after mating and
      their oocytes/embryos evaluated at four time periods after treatment. SETTING:
      Academic research environment. ANIMAL(S): Male and female CBAB(6) mice.
      INTERVENTION(S): Female mice were injected intraperitoneally with 5 IU
      gonadotropin (hCG) to stimulate follicular growth and induce ovulation. They were
      each caged with a male that had been gavaged with sildenafil citrate (0.06
      mg/0.05 mL) and allowed to mate. After 12, 36, 60, and 84 h, females were killed,
      their oviducts were dissected out, and retrieved embryos were assessed for
      blastomere number and quality. MAIN OUTCOME MEASURE(S): Fertilization rates and
      numbers of embryos were evaluated after treatment. RESULT(S): Fertilization rates
      (day 1) were markedly reduced (-33%) in matings where the male had taken
      sildenafil citrate. Over days 2-4, the numbers of embryos developing in the
      treated group were significantly fewer than in the control group. There was also
      a trend for impaired cleavage rates within those embryos, although this did not
      reach significance. CONCLUSION(S): The impairments to fertility caused by
      sildenafil citrate have important implications for infertility centers and for
      couples who are using this drug precoitally while attempting to conceive.

PMID- 18325512
TI  - Insulin resistance, hypercortisolism, polycystic ovarian syndrome, and depression
      -nonrandom associations?

PMID- 18325513
TI  - More education in the diagnosis and management of sexual dysfunction is needed.

PMID- 18325514
TI  - Endometrial osseous metaplasia: an evolving cause of secondary infertility.
AB  - OBJECTIVE: To present an endometrial osseous metaplasia case and reemphasize that
      the condition is a cause of secondary infertility. DESIGN: Case report. SETTING:
      Department of Obstetrics and Gynecology in a university hospital in Turkey.
      PATIENT(S): A 33-year-old multiparous woman was admitted to our institution with
      secondary infertility that had lasted for 2 years. She had experienced one first
      trimester and one second-trimester abortion, 3 years and 2 years ago,
      respectively. On transvaginal sonography, a linear curvy echogenity was observed.
      INTERVENTION(S): Hysteroscopic examination revealed multiple bony spicules,
      extending perpendicularly from the posterior uterine wall in to the uterine
      cavity and occupying almost two thirds of the cavity. Thereafter, a resectoscopic
      excision of the bony spicules was performed. MAIN OUTCOME MEASURE(S): A normal
      endometrium and uterine cavity. RESULT(S): Two weeks after the operation,
      ultrasonographic evaluation was in the normal range, and the patient currently is
      trying to conceive spontaneously. CONCLUSION(S): Although the role of office
      hysteroscopy in the evaluation of infertile couple is still under debate,
      clinicians should keep this rare disorder in mind, especially in patients with a
      history of late abortion, and should evaluate such cases by hysteroscopy when
      sonographic features are encountered.

PMID- 18325516
TI  - Effect of ovarian hormones on serum adiponectin and resistin concentrations.
AB  - OBJECTIVE: To investigate the effect of ovarian hormones on adiponectin and
      resistin levels in women. DESIGN: Experimental study. SETTING: University
      hospital. PATIENT(S): Thirteen normally cycling women (7 in group 1 and 6 in
      group 2) and 8 postmenopausal women (group 3). INTERVENTION(S): Women of group 1
      were investigated in a control cycle and in a subsequent cycle in which total
      abdominal hysterectomy plus bilateral salpingooophorectomy (TAH+BSO) was
      performed on day 3. In both cycles, the women received increasing doses of E(2)
      from days 3 to 5. Women of group 2 underwent TAH+BSO on day 3 without receiving
      any hormonal treatment. Women of group 3 received increasing doses of E(2) for 15
      days. MAIN OUTCOME MEASURE(S): Adiponectin, resistin, and E(2) concentrations.
      RESULT(S): In group 1, serum adiponectin and resistin levels did not show any
      significant changes for the week following day 3 and were similar in the two
      cycles. In group 2, adiponectin and resistin levels were similar before and after
      TAH+BSO and remained stable during the first postoperative week. In group 3, no
      significant changes in adiponectin and resistin levels were seen during the 15
      days of E(2) administration. CONCLUSION(S): Adiponectin and resistin values were
      not affected either by estrogen treatment or after ovariectomy in women. It is
      suggested that ovarian hormones are not involved in the regulation of adiponectin
      and resistin secretion in women.

PMID- 18325517
TI  - From oocyte to baby: a clinical evaluation of the biological efficiency of in
      vitro fertilization.
AB  - OBJECTIVE: To assess the real biological efficiency of assisted reproduction
      technology (ART) cycles by using a new metric called oocyte to baby rate, where
      live babies born (LBB) are reported in relation to the number of oocytes
      retrieved and used. DESIGN: Retrospective analysis of clinical and embryological
      database. SETTING: University center. PATIENT(S): Patient's cycles (n = 572)
      divided by age (<35, 35 to 37, 38 to 40, 41 to 42, >42 years) and by oocyte
      donors. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Total number of oocytes
      collected, the number of embryos transferable (fresh and frozen) and
      corresponding oocyte to LBB rates. In patients with remaining frozen embryos, the
      final LBB was estimated according to our reported rates. RESULT(S): A total of
      572 oocyte retrievals yielded 7213 oocytes. The total number of transferred and
      frozen embryos was 2252 (a utilization rate of 31.2%). The LBB from fresh embryo
      transfers was 262 with an additional 64 LBB expected from frozen embryos. The
      overall oocyte to LBB rate was 4.6% (326 babies born). When analyzed by groups,
      the oocyte to baby rate was best in donor oocyte cycles (6.8%), and declined to
      1% for patients >40. There was no increase in oocyte to LBB if >15 oocytes were
      obtained. CONCLUSION(S): During ART cycles, only approximately 5% of fresh
      oocytes produce a baby. The time has come to investigate new methods of oocyte
      viability assessment and consider changing current ART practice to recruit fewer
      oocytes.

PMID- 18325518
TI  - The resting frontal alpha asymmetry across the menstrual cycle: a
      magnetoencephalographic study.
AB  - Gonadotropic hormones play an important role in the regulation of emotion.
      Previous studies have demonstrated that estrogen can modulate appetitive
      (approach/positive) and aversive (avoidance/negative) affective behaviors during
      the menstrual cycle. Frontal alpha asymmetry (a measure of relative difference of
      the alpha power between the two anterior hemispheres) has been associated with
      the trait and state reactivity of different affective styles. We studied the
      pattern change of frontal alpha asymmetry across the menstrual cycle. 16 healthy
      women participated in this resting magneto-encephalographic (MEG) study during
      the peri-ovulatory (OV) and menstrual (MC) phases. Our results showed significant
      interaction of resting MEG alpha activity between hemispheric side and menstrual
      phases. Difference in spontaneous frontal alpha asymmetry pattern across the
      menstrual cycle was also noted. Relatively higher right frontal activity was
      found during the OV phase; relatively higher left frontal activity was noted
      during the MC phase. The alteration of frontal alpha asymmetry might serve a sub
      clinical correlate for hormonal modulation effect on dynamic brain organization
      for the predisposition and conceptualization of different affective styles across
      the menstrual cycle.

PMID- 18325519
TI  - Utility of optic nerve ultrasonography in head injury.
AB  - BACKGROUND: CT has evolved as the gold standard for evaluation of head injury,
      but early CT is not always possible. Bedside ultrasonography is available in most
      trauma units and optic nerve ultrasound (ONUS) examination should be feasible.
      OBJECTIVE: To evaluate the role of ONUS for people with head injury. SETTING:
      Tertiary care trauma service in a teaching hospital in a large metropolitan city
      in India. DESIGN: Prospective, blinded, observational study. METHODS: From April
      2006 to January 2007, all adult patients with head injury but without obvious
      ocular trauma, for whom it was possible to perform CT, were enrolled. Using a 7.5
      MHz ultrasonographic probe on the closed eyelids, optic nerve sheath diameter
      (ONSD) was measured on either side. A mean binocular ONSD less than 5.00 mm was
      considered normal. Cranial CT findings were used as a reference standard to
      evaluate ONUS. RESULTS: The study included 100 participants (72 men, 28 women,
      median age 28 years, median Glasgow Coma Scale score 11). Clinical features did
      not correlate with CT for signs of raised intracranial pressure (ICP). The mean
      binocular ONSD (5.8+/-0.57 mm) was significantly increased among individuals with
      signs of raised ICP on CT compared with the mean ONSD (3.5+/-0.75 mm) among those
      without such signs. ONUS revealed evidence of raised ICP in 74 cases (confirmed
      by CT in 72 cases), 59 of whom had significant intracranial haematoma needing
      surgical evacuation. Of the 26 cases with negative ONUS, confirmed by CT in 25
      cases, only 1 needed surgical intervention for drainage of intracranial
      haematoma. ONUS was false positive for two and false negative for one person. The
      sensitivity of ONUS in detecting elevated ICP was 98.6%, specificity 92.8%,
      positive predictive value 97.26% and negative predictive value 96.3%. CONCLUSION:
      ONUS has potential as a sensitive bedside screening test for detecting raised ICP
      and the presence of intracranial haematoma needing surgical intervention in adult
      head injury. This can be of immense help for unstable patients, in mass casualty
      situations and in remote locations.

PMID- 18325520
TI  - Population-related differences in fetal aortic arch dimensions.

PMID- 18325521
TI  - Identifying biomarkers of endometriosis using serum protein fingerprinting and
      artificial neural networks.
AB  - OBJECTIVES: To use surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry (SELDI-TOF-MS) protein chip array technology to detect
      proteomic patterns in the serum of women with endometriosis; build diagnostic
      models; and evaluate their clinical significance. METHODS: Serum samples from
      women with endometriosis and healthy women were studied using SELDI-TOF-MS
      protein chip technology. For every matched pair, two-thirds of the samples were
      used to look for different patterns and one-third was used for cross-validation.
      RESULTS: Five potential biomarkers were found and the diagnostic system
      distinguished endometriosis from validation samples with a sensitivity of 91.7%
      and a specificity of 90.0%. CONCLUSION: This method shows great potential in
      identifying biomarkers to be used for endometriosis screening.

PMID- 18325522
TI  - The value of reflective journaling in undergraduate nursing education: a
      literature review.
AB  - OBJECTIVES: The purpose of this literature review was to ascertain the evidence
      for the use of reflective journaling as a tool to promote the pedagogical
      strategy of reflection for the purpose of learning from practice for practice in
      undergraduate nursing education. DESIGN: Concept-centric. DATA SOURCES: The
      literature review involved structured searches of all OVID gateway databases,
      EBSCO host databases, and Blackwell Synergy. Qualitative and Quantitative Studies
      from 1992 to 2006 were included if they focused on reflective journaling in
      undergraduate clinical education. REVIEW METHODS: Due to the vast plethora of
      literature on reflection, keywords were utilized to focus the search.
      Approximately 150 abstracts were reviewed for primary sources of research. A
      total of nine studies met the inclusion criteria. The review subsequently divided
      the literature into four content themes allowing for appraisal and analysis of
      the findings, followed by summary and key recommendations for nursing education
      and research. RESULTS: There was evidence that educators struggle to incorporate
      reflective processes into education; however, the research provided rationale and
      support for engaging undergraduate students in the reflective process.
      Researchers found reasonable levels of reflection in undergraduate students'
      journaling and educators reported students' learning as a result of reflective
      journaling. Further to this, there was evidence that writing reflectively
      improved over time; a learned skill also dependent on a good facilitator and
      trust. Unfortunately, there was a paucity of research that explored the
      undergraduate nurses' experiences with the process of having to create written
      communication, with a critical reflective focus on practice. CONCLUSION: Nursing
      educators are correct in pursuing the teaching and learning of the reflective
      process in undergraduate nursing education. Nurse educators need to utilize
      various tools and strategies for facilitating the growth of undergraduate
      students into reflective practitioners. Indeed there was only limited evidence to
      support reflective journaling as an appropriate tool to promote reflection for
      the purpose of learning from practice for practice in undergraduate nursing
      education. Research that provides insight into the undergraduate student
      experience and perceptions of reflective journaling is needed to facilitate the
      structuring and use of reflective journaling as a tool in undergraduate nursing
      education.

PMID- 18325523
TI  - Spatial distribution of soil contamination by Toxoplasma gondii in relation to
      cat defecation behaviour in an urban area.
AB  - In urban areas, there may be a high local risk of zoonosis due to high densities
      of stray cat populations. In this study, soil contamination by oocysts of
      Toxoplasma gondii was searched for, and its spatial distribution was analysed in
      relation to defecation behaviour of cats living in a high-density population
      present in one area of Lyon (France). Sixteen defecation sites were first
      identified. Cats were then repeatedly fed with marked food and the marked faeces
      were searched for in the defecation sites. Of 260 markers, 72 were recovered from
      24 different cats. Defecation sites were frequented by up to 15 individuals. Soil
      samples were also examined in order to detect the presence of T. gondii using
      real-time PCR. The entire study area was then sampled according to cat density
      and vegetation cover type. Only three of 55 samples were positive and all came
      from defecation sites. In a second series of observations, 16 defecation sites
      were sampled. Eight of 62 samples tested positive, originating in five defecation
      sites. Laboratory experiments using experimental seeding of soil showed that the
      inoculated dose that can be detected in 50% of assays equals 100-1000oocysts/g,
      depending on the strain. This study shows that high concentrations of oocysts can
      be detected in soil samples using molecular methods and suggests that spatial
      distribution of contamination areas is highly heterogeneous. Positive samples
      were only found in some of the defecation sites, signifying that at-risk points
      for human and animal infection may be very localised.

PMID- 18325524
TI  - Simple and rapid instrumental characterization of sensory attributes of virgin
      olive oil based on the direct coupling headspace-mass spectrometry.
AB  - A methodology for obtaining reliable qualitative and quantitative information
      about negative (fusty, muddy sediment, musty, rancid and vinegary) and positive
      (fruity) sensory attributes of virgin olive oils (lampante and extra) has been
      developed. The procedure implies the joint use of a headspace autosampler, a mass
      spectrometer and an adequate chemometric data treatment. For this purpose, soft
      independent modelling of class analogy (SIMCA) and partial least squares (PLS)
      regression approaches were used for attribute identification and quantification,
      respectively. InStep application was employed to generate a decision tree by the
      combination of both models in order to provide the joint prediction of the
      sensory attributes of a given virgin olive oil and their respective intensities
      by means of a single output result. The good prediction results obtained when the
      decision tree generated were applied to a new set of virgin olive oil samples
      (viz, a specificity of 100%, an average sensitivity of 86% and a RMSEP<0.8% in
      the quantification task) reveals its potential applicability in routine analysis.

PMID- 18325525
TI  - Profiling of different bioactive compounds in functional drinks by high
      performance liquid chromatography.
AB  - In the present work, an HPLC method is proposed to simultaneously detect and
      quantify water- and fat-soluble vitamins, phenolic compounds, carotenoids and
      chlorophylls in a single run, by using an ultradeactivated C18 column and
      gradient separation using trifluoroacetic acid, water and methanol. It is shown
      that the HPLC method provides baseline separation of all these compounds with
      good resolution values in 40 min. Moreover, other figures of merit of the method
      show a good linear response and low detection limits for all the compounds
      considered in the present study. Furthermore, the usefulness of this method is
      demonstrated via its successful application to the analysis of different
      beverages from different natural origin (orange, strawberry, apple, peach
      pineapple, plum and blackcurrant juices, soybean milk, beers) without the need of
      any previous sample preparation. A good correlation is also found by comparing
      the total phenol content (measured by Folin-Ciocalteu method) with the sum of
      total phenolic compounds obtained using the proposed HPLC method. By using
      statistical tools, the main compounds associated with antioxidant activity of the
      extracts (measured by 1,1-diphenyl-2-picrylhydrazyl radical scavenging) were
      assessed.

PMID- 18325526
TI  - Preparation and evaluation of solid-phase microextraction fiber based on
      molecularly imprinted polymers for trace analysis of tetracyclines in complicated
      samples.
AB  - Molecularly imprinted polymer (MIP) is widely used in many fields because of its
      characteristics of high selectivity, chemical stability and easy preparation. To
      enhance the selectivity and applicability of solid-phase microextraction (SPME),
      a novel MIP-coated SPME fiber was firstly prepared by multiple co-polymerization
      method with tetracycline as template. It could be coupled directly to high
      performance liquid chromatography (HPLC) and used for trace analysis of
      tetracyclines (TCs) in complicated samples. The characteristics and application
      of the fibers were investigated. The electron microscope provided a crosslinked
      and porous surface, and the average thickness of the MIP coating was 19.5 microm.
      Compared with the non-imprinted polymer (NIP) coated fibers, the special
      selectivity to tetracycline and structure-similar oxytetracycline, doxycycline,
      chlortetracycline were discovered with the MIP-coated fibers. The adsorption and
      desorption of TCs with the MIP-coated fiber could be achieved quickly. A method
      for the fluorimetric determination of four TCs by the MIP-coated SPME coupled
      with HPLC was developed. The optimized extraction conditions such as extraction
      solvent, desorption solvent, and stirring speed were studied. Linear ranges for
      the four TCs were 5.00-200 microg/L and detection limits were within the range of
      1.0-2.3 microg/L. The method was applied to simultaneous multi-residue analysis
      of four TCs in the spiked chicken feed, chicken muscle, and milk samples with the
      satisfactory recoveries.

PMID- 18325527
TI  - Synthesis and characterization of mesoporous silica modified with chiral
      auxiliaries for their potential application as chiral stationary phase.
AB  - Novel chiral stationary phase (CSP) based on chiral aminoalcohol immobilized on
      ordered mesoporous silica SBA-15 1a and standard silica 1b and their copper
      complexes 1a' and 1b', respectively, was synthesized as potential material for
      chiral ligand exchange chromatography (CLEC). Microanalysis, inductively coupled
      plasma spectroscopy (ICP), thermo-gravimetric analysis (TGA), cross polarized
      magic angle spinning (CP-MAS) (13)C NMR, Powder X-ray diffraction (PXRD), FTIR,
      N(2) adsorption isotherm, scanning electron microscopy (SEM), transmitted
      electron microscope (TEM) and solid reflectance UV-vis spectroscopy were used to
      characterize these materials. All the chiral stationary phases thus synthesized
      were used for the separation of different racemic compounds such as mandelic
      acid, 2,2'-dihydroxy-1,1'-binaphthalene BINOL) and diethyl tartrate by simple
      medium-pressure column chromatography. Successful enantio-separation of racemic
      mandelic acid was achieved with all the stationary phases but 1a and 1b gave
      slightly better resolution than their copper complexes 1a' and 1b'. Remarkably
      these materials are stable under the given experimental conditions and can be
      used repeatedly for several cycles of enantioresolution. It was observed that the
      porosity and surface area of the stationary phase play an important role in the
      chiral separation.

PMID- 18325528
TI  - Effect of carbon nanofiber functionalization on the adsorption properties of
      volatile organic compounds.
AB  - The effect of the chemical activation, using HNO3, of a commercial carbon
      nanofiber (CNF) on its surface chemistry and adsorption properties is studied in
      this work. The adsorption of different alkanes (linear and cyclic), aromatic
      compounds and chlorohydrocarbons on both the parent and the oxidized CNF were
      compared. Temperature-programmed desorption results, in agreement with X-ray
      photoelectron spectroscopy experiments, reveal the existence of oxygen groups on
      the surface of the treated CNF. Capacity of adsorption was derived from the
      adsorption isotherms, whereas thermodynamic properties (enthalpy of adsorption,
      surface free energy characteristics) have been determined from chromatographic
      retention data. Both the capacity and the strength of adsorption decrease after
      the oxidant treatment of the carbon nanofibers, although in the case of
      chlorinated compounds the specific component of the surface energy shows an
      important increase. For n-alkanes and cyclic compounds, it was demonstrated that
      the presence of oxygen surface groups does not affect their interaction, the
      morphology of the surface being the key parameter. The oxidation of the nanofiber
      leads to steric limitations of the adsorption. In the adsorption of aromatic
      compounds, these limitations are compensated by the nucleophilic interactions
      between the aromatic ring and surface oxygenated groups, leading to similar
      performances of both materials. The absence of nucleophilic groups in the
      chlorinated compounds hinders their adsorption on the activated nanofibers.

PMID- 18325529
TI  - Removal of bovine serum albumin using solid-phase extraction with in-situ
      polymerized stationary phase in a microfluidic device.
AB  - Serum albumin, one of the most abundant serum proteins, blocks the expression of
      other important biomarkers. The objective of this study is to remove serum
      albumin effectively by using solid-phase extraction (SPE) in microfluidic
      devices. Photo-polymerized adsorbent as a stationary phase of SPE was used to
      remove bovine serum albumin (BSA). The adsorption capacity was examined with the
      effect of pH and concentration in BSA solution, and adjustment of monomer
      concentration such as hydrophilic 2-acrylamido-2-methyl-1-propanesulfonic acid
      and acrylamide in the adsorbent. The effect of hydrophobic butyl methacylate on
      BSA adsorption was also studied. Selective removal in a bicomponent with BSA and
      bovine gamma-globulin was performed by adjusting the pH as required.

PMID- 18325530
TI  - Effect of non-homogeneous surface viscosity on the Marangoni migration of a
      droplet in viscous fluid.
AB  - Marangoni migration of a single droplet in an unbounded viscous fluid under the
      additional effect of variable surface viscosity is studied. The surface tension
      and the surface viscosity depend on concentration of dissolved species. Cases of
      the motion induced by the presence of a point source and by a given constant
      concentration gradient are considered. The dependence of the migration velocity
      on the governing parameters is computed under quasi-stationary approximation. The
      effect of weak advective transport is studied making use of singular
      perturbations in the Peclet number, Pe. It is shown that, when the source is time
      dependent a Basset-type history term appears in the expansion of the
      concentration and, as a result, the leading order correction to the flow and to
      the migration velocity is of O(Pe(1/2)). If the source of active substance
      driving the flow is steady, the effect of convective transport on the migration
      is weaker.

PMID- 18325531
TI  - Cross-cultural perspectives on pitch memory.
AB  - We examined effects of age and culture on children's memory for the pitch level
      of familiar music. Canadian 9- and 10-year-olds distinguished the original pitch
      level of familiar television theme songs from foils that were pitch-shifted by
      one semitone, whereas 5- to 8-year-olds failed to do so (Experiment 1). In
      contrast, Japanese 5- and 6-year-olds distinguished the pitch-shifted foils from
      the originals, performing significantly better than same-age Canadian children
      (Experiment 2). Moreover, Japanese 6-year-olds were more accurate than their 5
      year-old counterparts. These findings challenge the prevailing view of enhanced
      pitch memory during early life. We consider factors that may account for Japanese
      children's superior performance such as their use of a pitch accent language
      (Japanese) rather than a stress accent language (English) and their experience
      with musical pitch labels.

PMID- 18325532
TI  - Mutants in DsbB that appear to redirect oxidation through the disulfide
      isomerization pathway.
AB  - Disulfide bond formation occurs in secreted proteins in Escherichia coli when the
      disulfide oxidoreductase DsbA, a soluble periplasmic protein, nonspecifically
      transfers a disulfide to a substrate protein. The catalytic disulfide of DsbA is
      regenerated by the inner-membrane protein DsbB. To help identify the specificity
      determinants in DsbB and to understand the nature of the kinetic barrier
      preventing direct oxidation of newly secreted proteins by DsbB, we imposed
      selective pressure to find novel mutations in DsbB that would function to bypass
      the need for the disulfide carrier DsbA. We found a series of mutations localized
      to a short horizontal alpha-helix anchored near the outer surface of the inner
      membrane of DsbB that eliminated the need for DsbA. These mutations changed
      hydrophobic residues into nonhydrophobic residues. We hypothesize that these
      mutations may act by decreasing the affinity of this alpha-helix to the membrane.
      The DsbB mutants were dependent on the disulfide oxidoreductase DsbC, a soluble
      periplasmic thiol-disulfide isomerase, for complementation. DsbB is not normally
      able to oxidize DsbC, possibly due to a steric clash that occurs between DsbC and
      the membrane adjacent to DsbB. DsbC must be in the reduced form to function as an
      isomerase. In contrast, DsbA must remain oxidized to function as an oxidizing
      thiol-disulfide oxidoreductase. The lack of interaction that normally exists
      between DsbB and DsbC appears to provide a means to separate the DsbA-DsbB
      oxidation pathway and the DsbC-DsbD isomerization pathway. Our mutants in DsbB
      may act by redirecting oxidant flow to take place through the isomerization
      pathway.

PMID- 18325533
TI  - Energetic coupling between native-state prolyl isomerization and conformational
      protein folding.
AB  - In folded proteins, prolyl peptide bonds are usually thought to be either trans
      or cis because only one of the isomers can be accommodated in the native folded
      protein. For the N-terminal domain of the gene-3 protein of the filamentous phage
      fd (N2 domain), Pro161 resides at the tip of a beta hairpin and was found to be
      cis in the crystal structure of this protein. Here we show that Pro161 exists in
      both the cis and the trans conformations in the folded form of the N2 domain. We
      investigated how conformational folding and prolyl isomerization are coupled in
      the unfolding and refolding of N2 domain. A combination of single-mixing and
      double-mixing unfolding and refolding experiments showed that, in unfolded N2
      domain, 7% of the molecules contain a cis-Pro161 and 93% of the molecules contain
      a trans-Pro161. During refolding, the fraction of molecules with a cis-Pro161
      increases to 85%. This implies that 10.3 kJ mol(-1) of the folding free energy
      was used to drive this 75-fold change in the Pro161 cis/trans equilibrium
      constant during folding. The stabilities of the forms with the cis and the trans
      isomers of Pro161 and their folding kinetics could be determined separately
      because their conformational folding is much faster than the prolyl isomerization
      reactions in the native and the unfolded proteins. The energetic coupling between
      conformational folding and Pro161 isomerization is already fully established in
      the transition state of folding, and the two isomeric forms are thus truly native
      forms. The folding kinetics are well described by a four-species box model, in
      which the N2 molecules with either isomer of Pro161 can fold to the native state
      and in which cis/trans isomerization occurs in both the unfolded and the folded
      proteins.

PMID- 18325534
TI  - Conformational changes and reaction of clostridial glycosylating toxins.
AB  - The crystal structures of the catalytic fragments of 'lethal toxin' from
      Clostridium sordellii and of 'alpha-toxin' from Clostridium novyi have been
      established. Almost half of the residues follow the chain fold of the glycosyl
      transferase type A family of enzymes; the other half forms large alpha-helical
      protrusions that are likely to confer specificity for the respective targeted
      subgroup of Rho proteins in the cell. In the crystal, the active center of alpha
      toxin contained no substrates and was disassembled, whereas that of lethal toxin,
      which was ligated with the donor substrate UDP-glucose and cofactor Mn2+, was
      catalytically competent. Surprisingly, the structure of lethal toxin with Ca2+
      (instead of Mn2+) at the cofactor position showed a bound donor substrate with a
      disassembled active center, indicating that the strictly octahedral coordination
      sphere of Mn2+ is indispensable to the integrity of the enzyme. The homologous
      structures of alpha-toxin without substrate, distorted lethal toxin with Ca2+
      plus donor, active lethal toxin with Mn2+ plus donor and the homologous
      Clostridium difficile toxin B with a hydrolyzed donor have been lined up to show
      the geometry of several reaction steps. Interestingly, the structural refinement
      of one of the three crystallographically independent molecules of Ca2+-ligated
      lethal toxin resulted in the glucosyl half-chair conformation expected for
      glycosyl-transferases that retain the anomeric configuration at the C1'' atom. A
      superposition of six acceptor substrates bound to homologous enzymes yielded the
      position of the nucleophilic acceptor atom with a deviation of <1 A. The
      resulting donor-acceptor geometry suggests that the reaction runs as a circular
      electron transfer in a six-membered ring, which involves the deprotonation of the
      nucleophile by the beta-phosphoryl group of the donor substrate UDP-glucose.

PMID- 18325535
TI  - Relapsing Guillain Barre Syndrome and nephrotic syndrome secondary to focal
      segmental glomerulosclerosis.
AB  - A 49-year-old man developed simultaneously a Guillain Barre Syndrome (GBS) and a
      nephrotic syndrome (NS). The patient relapsed twice, despite treatment with
      intravenous immunoglobulins (IVIg) after a full or partial recovery, and became
      resistant to IVIg. Renal biopsy revealed focal segmental glomerulosclerosis
      (FSGS). He responded to plasmapheresis and corticosteroids with simultaneous
      recovery of his GBS and NS, suggesting a common pathogenesis of the two
      conditions.

PMID- 18325536
TI  - Carpal tunnel syndrome in postmenopausal women.
AB  - OBJECTIVE: Hormonal changes that accompany menopause have a significant impact on
      the nervous and other physiological systems. Our objective was to evaluate the
      relationship between carpal tunnel syndrome (CTS) and the clinical features of
      menopause in postmenopausal women, in comparison to age-matched healthy controls.
      METHODS: Overall, 6230 women were seen during the study period. Of these, 5587
      were not eligible because they were premenopausal or perimenopausal. 537 women
      did not meet the criteria used in the study for a diagnosis of idiopathic CTS and
      were excluded. Finally, one hundred and six patients with CTS and 115 controls
      were examined. The presence of CTS was confirmed both clinically and
      electrophysiologically. Socio-demographic variables and reproductive histories
      were evaluated via a structured interview. RESULTS: In comparison to healthy
      controls, patients with CTS showed a significantly greater number of pregnancies
      and an earlier age at menopause. Regarding the type of menopause, patients and
      controls showed similar frequencies for natural versus surgical menopause. The
      frequency of natural menopause was significantly higher than that of surgical
      menopause in both groups. CONCLUSION: Our results suggest that age at menopause
      may be a significant factor in the development of CTS. Pregnancy-related hormonal
      changes may have long-term effects that increase the incidence of CTS in
      postmenopausal women.

PMID- 18325537
TI  - Evaluation of ActiTrac (ambulatory activity monitor) in Parkinson's Disease.
AB  - At present, the evaluation of Parkinson's Disease (PD) relies mainly on Unified
      Parkinson's Disease Rating Scale (UPDRS). Other objective measures have been
      proposed, including functional studies, timed tests and ambulatory activity
      monitors (AAM). We carried out a prospective study to analyze the utility and
      correlation of the AAM: ActiTrac with UPDRS scores and timed tests in patients
      with PD. We studied 28 patients with idiopathic PD (age: 62 +/- 11 years;
      duration of illness: 7.7 +/- 4.4 years; clinical stage 2.3 +/- 0.39). Motor
      evaluation included UPDRS and five timed tests: Purdue Pegboard test and those
      proposed in CAPIT protocol, pronation-supination (PS), finger dexterity (FD),
      movement between two points (MTP) and walking test (WT). Clinical evaluation was
      performed in off condition, at 9 a.m., (12h off their medication). Finally,
      ActiTrac was placed on the wrist (more affected side) continuously for at least
      72h. ActiTrac activity was correlated (Spearman) with total UPDRS (r: - 0.53, p <
      0.005) and motor UPDRS (r:- 0.46, p: 0.01); UPDRS rigidity subscore (r:- 0.52, p
      < 0.01); UPDRS bradykinesia subscore (r:- 0.48; p:0.01); FD (r: - 0.47 p: 0.01),
      WT (r: - 0.49, p < 0.01) and Purdue test (r:0.54; p < 0.01). ActiTrac seems to be
      a reasonably accurate method to evaluate motor activity in PD.

PMID- 18325538
TI  - Backward bifurcations and multiple equilibria in epidemic models with structured
      immunity.
AB  - Many disease pathogens stimulate immunity in their hosts, which then wanes over
      time. To better understand the impact of this immunity on epidemiological
      dynamics, we propose an epidemic model structured according to immunity level
      that can be applied in many different settings. Under biologically realistic
      hypotheses, we find that immunity alone never creates a backward bifurcation of
      the disease-free steady state. This does not rule out the possibility of multiple
      stable equilibria, but we provide two sufficient conditions for the uniqueness of
      the endemic equilibrium, and show that these conditions ensure uniqueness in
      several common special cases. Our results indicate that the within-host dynamics
      of immunity can, in principle, have important consequences for population-level
      dynamics, but also suggest that this would require strong non-monotone effects in
      the immune response to infection. Neutralizing antibody titer data for measles
      are used to demonstrate the biological application of our theory.

PMID- 18325539
TI  - The spatial and temporal distribution of heavy metals in sediments of Victoria
      Harbour, Hong Kong.
AB  - Victoria Harbour has received substantial loadings of pollutants from industrial
      and municipal wastewater discharged since the 1950s. Inputs of contaminants have
      declined dramatically during the last two decades as a result of better controls
      at the source and improved wastewater treatment facilities. To assess the spatial
      and temporal changes of metal contaminants in sediments in Victoria Harbour, core
      and grab sediments were collected. The central harbour areas were generally
      contaminated with heavy metals. The spatial distribution of trace metals can
      probably be attributed to the proximity of major urban and industrial discharge
      points, and to the effect of tidal flushing in the harbour. In the sediment
      cores, the highest concentrations of trace metals were observed to have
      accumulated during the 1950s-1980s, corresponding with the period of rapid urban
      and industrial development in Hong Kong. From the late 1980s, there has been a
      major decline in the concentrations of trace metals, due to a reduction in
      industrial activities and to the enactment of wastewater pollution controls in
      the territory. The Pb isotopic compositions of the sediments revealed the
      anthropogenic inputs of Pb to the harbour. The (206)Pb/(207)Pb ratios varied from
      1.154 to 1.190, which were lower than those of background geological materials in
      Hong Kong ((206)Pb/(207)Pb: 1.201-1.279). The data also indicated that the Pb in
      the harbour sediments most likely originated from mixed sources, including the
      leaded gasoline used in the past and other anthropogenic sources.

PMID- 18325540
TI  - Assessment of chemical dispersant effectiveness in a wave tank under regular non
      breaking and breaking wave conditions.
AB  - Current chemical dispersant effectiveness tests for product selection are
      commonly performed with bench-scale testing apparatus. However, for the
      assessment of oil dispersant effectiveness under real sea state conditions, test
      protocols are required to have hydrodynamic conditions closer to the natural
      environment, including transport and dilution effects. To achieve this goal,
      Fisheries and Oceans Canada and the US Environmental Protection Agency (EPA)
      designed and constructed a wave tank system to study chemical dispersant
      effectiveness under controlled mixing energy conditions (regular non-breaking,
      spilling breaking, and plunging breaking waves). Quantification of oil dispersant
      effectiveness was based on observed changes in dispersed oil concentrations and
      oil-droplet size distribution. The study results quantitatively demonstrated that
      total dispersed oil concentration and breakup kinetics of oil droplets in the
      water column were strongly dependent on the presence of chemical dispersants and
      the influence of breaking waves. These data on the effectiveness of dispersants
      as a function of sea state will have significant implications in the drafting of
      future operational guidelines for dispersant use at sea.

PMID- 18325541
TI  - Assessment of the ecological quality status of soft-bottoms in Reunion Island
      (tropical Southwest Indian Ocean) using AZTI marine biotic indices.
AB  - The ability of the two synthetic marine biotic indices, AMBI and M-AMBI, to
      account for changes in the ecological quality of coastal soft bottoms of Reunion
      Island according to disturbances was assessed from macrobenthic samples collected
      in five sectors between 1994 and 2004. Samples were collected under non-perturbed
      conditions and at two sites subjected to heavy organic enrichment. Both indices
      are based on a classification of macrofauna into ecological groups (EG), and
      their transfer to tropical waters required some adaptations. These indices proved
      efficient in detecting a degradation of habitat quality. Their use resulted in
      the classification of all sites sampled between 1996 and 1998 as "good" or
      "high". M-AMBI nevertheless tended to result in the attribution of a slightly
      worse ecological quality status than AMBI. Together with an update of the EG
      species list for the Indian Ocean area, our results support the extension of both
      indices for the assessment of tropical soft bottoms.

PMID- 18325542
TI  - Delay abolishes the obstacle avoidance deficit in unilateral optic ataxia.
AB  - Optic ataxic patients have deficits in the visual control of manual reaching and
      grasping. It has been established previously that these deficits in target
      directed behaviour improve following a delay in response. Recently it has been
      demonstrated that optic ataxic patients also have deficits in taking potential
      obstacles into account during reaching. The present study was therefore designed
      to test whether delay would bring an improvement in this behaviour as well. We
      present experimental data from a patient with unilateral optic ataxia (M.H.).
      First we document M.H.'s pointing errors, which show a reliable pattern of
      impairment when pointing to targets in his right visual field, particularly when
      using his right hand. We then show that a similar pattern of deficits is
      observable in his ability to negotiate between non-targets: that is, M.H.
      selectively fails to take account of obstacles in his right visual field, but
      only while reaching with his right hand. Finally we demonstrate that this
      obstacle avoidance deficit disappears following a 5s delay in response: under
      these conditions M.H. now takes account of both non-target objects with either
      hand. The results are interpreted within the 'two visual streams' model of
      cortical visual processing.

PMID- 18325543
TI  - The neural substrates of semantic memory deficits in early Alzheimer's disease:
      clues from semantic priming effects and FDG-PET.
AB  - The neural substrates responsible for semantic dysfunction during the early
      stages of AD have yet to be clearly identified. After a brief overview of the
      literature on normal and pathological semantic memory, we describe a new
      approach, designed to provide fresh insights into semantic deficits in AD. We
      mapped the correlations between resting-state brain glucose utilisation measured
      by FDG-PET and semantic priming scores in a group of 17 AD patients. The priming
      task, which yields a particularly pure measurement of semantic memory, was
      composed of related pairs of words sharing an attribute relationship (e.g. tiger
      stripe). The priming scores correlated positively with the metabolism of the
      superior temporal areas on both sides, especially the right side, and this
      correlation was shown to be specific to the semantic priming effect. This pattern
      of results is discussed in the light of recent theoretical models of semantic
      memory, and suggests that a dysfunction of the right superior temporal cortex may
      contribute to early semantic deficits, characterised by the loss of specific
      features of concepts in AD.

PMID- 18325544
TI  - Spreading activation of lexical-semantic networks in Parkinson's disease.
AB  - Although dopamine may act as a neuromodulator of spreading activation within
      semantic networks, this role of dopamine in lexical networks has not been
      investigated. Hence, we sought to investigate the effects of Parkinson's disease
      (PD), which is associated with dopamine depletion, on spreading activation in the
      lexical networks. Ten Parkinson's disease patients and 11 normal controls
      performed the controlled oral word association test and the average word
      frequency for their responses was calculated and used as an index of spreading
      activation. The PD patients exhibited a lower average word frequency, suggesting
      increased spreading activation, and a significant relationship between the
      strength of the initial activation and subsequent extent of spreading activation.
      Most patients were taking dopaminergic medication and future studies may benefit
      from examining the changes in spreading activation in lexical networks in PD
      patients on versus off medication or in healthy controls taking either a placebo
      or a dopaminergic medication. Although these alterations in lexical access might
      be related to the reduction of dopamine, one of the hallmarks of PD, these
      patients also have alterations of other neurotransmitter systems and further
      studies are needed to more clearly identify the role played by these
      neurotransmitter on lexical access.

PMID- 18325545
TI  - Effects of age of acquisition on brain activation during Chinese character
      recognition.
AB  - The age of acquisition of a word (AoA) has a specific effect on brain activation
      during word identification in English and German. However, the neural locus of
      AoA effects differs across studies. According to Hernandez and Fiebach
      [Hernandez, A., & Fiebach, C. (2006). The brain bases of reading late-learned
      words: Evidence from functional MRI. Visual Cognition, 13(8), 1027-1043], the
      effects of AoA on brain activation depend on the predictability of the
      connections between input (orthography) and output (phonology) in a lexical
      network. We tested this hypothesis by examining AoA effects in a non-alphabetic
      script with relatively arbitrary mappings between orthography and phonology-
      Chinese. Our results showed that the effects of AoA in Chinese speakers are
      located in brain regions that are spatially distinctive including the bilateral
      middle temporal gyrus and the left inferior parietal cortex. An additional
      finding was that word frequency had an independent effect on brain activation in
      the right middle occipital gyrus only. We conclude that spatially distinctive
      effects of AoA on neural activity depend on the predictability of the mappings
      between orthography and phonology and reflect a division of labour towards
      greater lexical-semantic retrieval in non-alphabetic scripts.

PMID- 18325547
TI  - Weakened biological signals: highly-developed eating schemas amongst women are
      associated with maladaptive patterns of comfort food consumption.
AB  - We examine the comfort food preferences and consumption patterns of women with
      highly versus less developed schemas for cognitive restraint, emotional and
      situational eating. In an online survey, 196 women provided their personal
      definition of what constitutes a comfort food, indicated their favourite one, and
      their level of hunger and fullness as well as emotional state before and after
      consumption. Low/high (n=32/n=30) schematic groups respectively scored
      below/above the median on all three factors of the Dutch Eating Behavior
      Questionnaire (DEBQ). Results support our proposition that complex eating schemas
      weaken biological signals and produce maladaptive patterns: high schematics
      preferred high calorie comfort foods, eaten even when feeling full to alleviate
      negative emotions at the cost of more post-consumption guilt. High schematics
      reported a lesser post-consumption increase in fullness than low schematics. Low
      schematics favoured low and high calorie foods equally, their choice motivated by
      pleasure and positive emotions. High schematics' definitions revealed that
      comfort foods are eaten to fill a void or when experiencing negative emotions as
      well as a deep concern with weight gain; low schematics focused on comfort foods'
      hedonic attributes. Our results highlight the hitherto unexplored influence of
      possessing all three highly-developed DEBQ eating schemas in reducing the
      effectiveness of biological signals and leading to maladaptive eating choices and
      behaviors.

PMID- 18325546
TI  - After daily bingeing on a sucrose solution, food deprivation induces anxiety and
      accumbens dopamine/acetylcholine imbalance.
AB  - Bingeing on sugar may activate neural pathways in a manner similar to taking
      drugs of abuse, resulting in related signs of dependence. The present experiments
      test whether rats that have been bingeing on sucrose and then fasted demonstrate
      signs of opiate-like withdrawal. Rats were maintained on 12-h deprivation
      followed by 12-h access to a 10% sucrose solution and chow for 28 days, then
      fasted for 36 h. These animals spent less time on the exposed arm of an elevated
      plus-maze compared with a similarly deprived ad libitum chow group, suggesting
      anxiety. Microdialysis revealed a concomitant increase in extracellular
      acetylcholine and decrease in dopamine release in the nucleus accumbens shell.
      These results did not appear to be due to hypoglycemia. The findings suggest that
      a diet of bingeing on sucrose and chow followed by fasting creates a state that
      involves anxiety and altered accumbens dopamine and acetylcholine balance. This
      is similar to the effects of naloxone, suggesting opiate-like withdrawal. This
      may be a factor in some eating disorders.

PMID- 18325548
TI  - Alternative reproductive tactics in male Cape ground squirrels Xerus inauris.
AB  - In some animal societies, males vary in the strategies and tactics that they use
      for reproduction. Explanations for the evolution of alternative tactics have
      usually focussed on extrinsic factors such as social status, the environment or
      population density and have rarely examined proximate differences between
      individuals. Anecdotal evidence suggests that two alternative reproductive
      tactics occur in cooperatively breeding male Cape ground squirrels. Here we show
      that there is strong empirical support for physiological and behavioural
      differences to uphold this claim. 'Dispersed' males have higher resting metabolic
      rates and a heightened pituitary activity, compared with philopatric 'natal'
      males that have higher circulating cortisol levels. Dispersed males also spend
      more time moving and less time feeding than natal males. Additionally, lone males
      spend a greater proportion of their time vigilant and less of their time foraging
      than those that were in groups. The choice of whether to stay natal or become a
      disperser may depend on a number of factors such as age, natal group kin
      structure and reproductive suppression, and the likelihood of successful
      reproduction whilst remaining natal. Measuring proximate factors, such as
      behavioural and endocrine function, may provide valuable insights into mechanisms
      that underlie the evolution of alternative reproductive tactics.

PMID- 18325549
TI  - 13C-labelling patterns of green leaf volatiles indicating different dynamics of
      precursors in Brassica leaves.
AB  - To investigate the dynamics of precursor compounds of green leaf volatiles (GLV)s
      and other biogenic compounds released by mechanically damaged Brassica oleracea
      leaves, plants were exposed for two consecutive 16h light phases to highly
      enriched (13)CO(2). Analysis by GC-MS indicated (1) biogenic compounds released
      upon wounding, (2) a different labelling pattern between and (3) within
      compounds, and (4) evidence for spatial heterogeneity of the precursor pool
      extrapolated from points (1)-(3). First, GLVs comprised C(5) and C(6) molecules,
      with the GLV pentenyl acetate being reported here for the first time from higher
      plants. Second, the labelling pattern found in most GLVs indicates a low turnover
      of the precursor alpha-linolenic acid. Moderate labelling of dimethyldisulphide
      indicates a connection to an active plastidic methyl pool closely connected to
      CO(2) fixation, and very weak labelling of terpenes indicates a constitutive
      monoterpene pool. Third, not all GLVs exhibit similarly strong labelling patterns
      (hexenyl acetate vs. hexyl acetate), indicating different precursors. As the
      labelling patterns of alcohol and acetate moieties in the esters differ, with
      only the former being strongly labelled, the precursor of the acetate moiety,
      acetyl-CoA, is likely to derive from a different cellular pool to that used in
      chloroplastic fatty acid synthesis, or was rapidly synthesised after the end of
      labelling. Fourth, the exceptionally high relative abundance of labelled GLV and
      the low concentration of unlabelled molecules are likely to occur because
      recently synthesized alpha-linolenic acid is bound in lipids that are organised
      in distinct areas, or are chemically different from the older lipids. They must
      be preferentially used as precursors.

PMID- 18325550
TI  - Identification of galloylated propelargonidins and procyanidins in buckwheat
      grain and quantification of rutin and flavanols from homostylous hybrids
      originating from F. esculentumxF. homotropicum.
AB  - The flavonoid rich grain of buckwheat (Fagopyrum esculentum Moench, Fam.
      Polygonaceae) is of high nutritional value. With the aim to improve its agronomic
      productivity, cultivars were crossed with the wild species F. homotropicum which,
      however, differs in its flavonoid content. The intention of this work was to
      determine the flavonoid composition in developed interspecific hybrids and to
      elucidate the proanthocyanidin structures. Seven compounds were purified from
      methanol extracts of buckwheat (Fagopyrum esculentum Moench) grains by Sephadex
      LH-20 column chromatography. Beside the procyanidin epicatechin-[4-8]-epicatechin
      3-O-(3,4)-dimethylgallate the following propelargonidins were identified:
      epiafzelechin-[4-6]-epicatechin, epiafzelechin-[4-8]-epiafzelechin-[4-8]
      epicatechin, epiafzelechin-[4-8]-epicatechin-3-O-(3,4-dimethyl)-gallate,
      epiafzelechin-[4-8]-epiafzelechin-[4-8]-epicatechin-3-O-(3,4-dimethyl)-gallate,
      epiafzelechin-[4-8]-epicatechin-3-O-4-methyl-gallate and epiafzelechin-[4-8]
      epicatechin-p-OH-benzoate on the basis of HPLC and LC-MS/MS.

PMID- 18325551
TI  - Purine-containing cucurbitane triterpenoids from Cucurbita pepo cv dayangua.
AB  - Phytochemical investigation of the fruits of Cucurbita pepo cv dayangua led to
      the isolation of cucurbitaglycosides A (1) and B (2). This is the first report of
      cucurbitane triterpenoids with a purine unit. Their structures were elucidated
      mainly based on interpretation of HRESIMS results, as well as 1D and 2D NMR
      spectra. Cucurbitaglycosides A and B showed cytotoxic activity against the human
      epithelial carcinoma cell line HeLa with IC50 of 17.2 and 28.4 microg/mL,
      respectively.

PMID- 18325552
TI  - Stereumin A-E, sesquiterpenoids from the fungus Stereum sp. CCTCC AF 207024.
AB  - Five cadinane sesquiterpenoids, named stereumin A (1), B (2), C (3), D (4) and E
      (5) were isolated from the CHCl(3) extract of the culture broth of the fungal
      strain CCTCC AF 207024. Based on the sequences at the internal transcribed spacer
      (ITS) region and partial 28S rDNA, this fungus was identified as a Stereum sp.
      The structures of the five compounds were elucidated using spectroscopic data
      from 1D, 2D NMR and HRESIMS experiments, and the structures of 1 and 2 were
      further confirmed by single-crystal X-ray diffraction analysis. Compounds 1-5
      showed nematicidal activities against the nematode Panagrellus redivivus at 400
      mg l(-1). Among these five compounds, compounds 3 and 4 killed 84.4% and 94.9% of
      P. redivivus, respectively in 48 h.

PMID- 18325553
TI  - Fractionation and characterization of biologically-active polysaccharides from
      Artemisia tripartita.
AB  - The leaves of Artemisia species have been traditionally used for prevention and
      treatment of a number of diseases. In this study, five polysaccharide fractions
      (designated A-I-A-V) were isolated from the leaves of Artemisia tripartita Rydb.
      by the sequential use of hot-water extraction, ethanol precipitation, ultra
      filtration, and chromatography. The homogeneity and average molecular weight of
      each fraction were determined by high performance size-exclusion chromatography.
      Sugar composition analysis revealed that Artemisia polysaccharides consisted
      primarily of xylose, glucose, arabinose, galactose, and galactosamine. Moreover,
      all fractions contained at least 3.4% sulfate, and fractions A-II-A-V contained
      an arabinogalactan type II structure. All fractions exhibited macrophage
      activating activity, enhancing production of intracellular reactive oxygen
      species and release of nitric oxide, interleukin 6, interleukin 10, tumor
      necrosis factor alpha, and monocyte chemotactic protein 1. In addition, all
      fractions exhibited scavenging activity for reactive oxygen species generated
      enzymatically or produced extracellularly by human neutrophils. Finally,
      fractions A-I and A-V exhibited complement-fixing activity. Taken together, our
      results provide a molecular basis to explain at least part of the beneficial
      therapeutic effects of Artemisia extracts, and suggest the possibility of using
      Artemisia polysaccharides as an immunotherapeutic adjuvant.

PMID- 18325554
TI  - Parasite contamination of soil in households of a Mexican rural community endemic
      for neurocysticercosis.
AB  - High neurocysticercosis (NC) prevalence was recently determined by a computed
      tomography (CT) scan study in the community of Tepetzitzintla, State of Puebla,
      Mexico. The aim of the present work was to evaluate the magnitude of fecal and
      parasite contamination by Taenia spp. in the soil of households of this community
      during the four seasons of the year. The toilet, backyard, kitchen, washboard,
      water containers and corrals of 14 to 26 households were sampled during each
      season. High Taenia spp. egg intensity was found in 24.2% of the sampled areas.
      The highest percentage was detected in Spring and the lowest in Summer.
      Significantly higher levels of Taenia spp. eggs were present in kitchen soil
      samples. A significant correlation was found between the presence of Taenia spp.
      eggs in household soil during the Summer, and NC diagnoses of the inhabitants by
      CT scan. Coproparasitological examinations and anti-cysticercal antibodies were
      determined in a cohort of inhabitants of the sampled households. Antibody levels
      and coproparasitological results were not associated with NC. Overall, these
      results illustrate the high degree of fecal contamination of potential risk to
      human health in rural communities and could be of use for control programmes.

PMID- 18325555
TI  - Synthesis of bis-diosgenin pyrazine dimers: new cephalostatin analogs.
AB  - A convenient synthesis for bis-diosgenin pyrazine dimers, cephalostatin analogues
      is reported. These symmetrical dimeric steroid-pyrazines were obtained by the
      classical condensation of alpha-amino ketones, the most efficient method for
      pyrazine ring construction.

PMID- 18325556
TI  - Synthesis and molecular structure of 14,15-pyrrolidino-and 14,16-ethano
      derivatives of estrone.
AB  - Hydrolysis of 3-methoxy-16alpha-nitro-14,17-ethenoestra-1,3,5(10)-trien-17beta-yl
      acetate under weakly basic conditions leads to formation of 3-methoxy-2'
      oxopyrrolidino-[4',5':14beta,15beta]-estra-1,3,5 (10)-trien-17-one, the structure
      of which has been confirmed by X-ray analysis and some chemical transformations.
      The reactivity of 3-methoxy-16alpha-nitro-14,17-ethanoestra-1,3,5(10)-trien
      17beta-yl acetate under various conditions of basic hydrolysis has been
      investigated. The derived compounds have been identified by means of NMR
      spectroscopy and X-ray analysis.

PMID- 18325557
TI  - Vascular cell signaling by membrane estrogen receptors.
AB  - The definition of estrogen's actions has expanded from transcriptional regulation
      to the rapid, membrane-initiated activation of numerous signal transduction
      cascades. Multiple biological effects of estrogen have been shown in numerous
      animals, cellular and molecular studies, which support the favorable effects of
      estrogen on vascular structure, function, and cell signaling. Work from several
      laboratories has shown that these effects are mediated by distinct forms of
      estrogen receptor (ER) alpha. This includes estrogen-stimulated rapid activation
      of endothelial nitric oxide synthase (eNOS), resulting in the elaboration of the
      athero-protective, angiogenesis-promoting product nitric oxide (NO). We have
      described the expression of ER46, an N-terminus truncated isoform of the ERalpha,
      in human endothelial cells (EC), and its critical role in membrane-initiated,
      rapid responses to 17beta-estradiol (E2). We have proposed an ER46-centered, eNOS
      activating molecular complex in human EC caveolar membranes, containing c-Src,
      phosphatidylinositol 3-kinase (PI3K), Akt and eNOS. Our previous studies support
      estrogen-induced rapid eNOS activation via a sequential c-Src/PI3K/Akt cascade in
      EC. In this review, we describe estrogen-induced, rapid, non-genomic actions in
      endothelium, driven by c-Src-ER46-caveolin-1 interactions, with consequent
      activation of eNOS. Amidst ongoing controversies in hormone replacement therapy,
      these molecular and cellular data, defining favorable estrogenic effects on the
      endothelium, provide a strong impetus to resolve these clinical questions.

PMID- 18325558
TI  - Roles of biomarkers in evaluating interactions among mixtures of lead, cadmium
      and arsenic.
AB  - Human exposure to environmental chemicals is most correctly characterized as
      exposure to mixtures of these agents. The metals/metalloids, lead (Pb), cadmium
      (Cd), and arsenic (As), are among the leading toxic agents detected in the
      environment. Exposure to these elements, particularly at chronic low dose levels,
      is still a major public health concern. Concurrent exposure to Pb, Cd, or As may
      produce additive or synergistic interactions or even new effects that are not
      seen in single component exposures. Evaluating these interactions on a
      mechanistic basis is essential for risk assessment and management of
      metal/metalloid mixtures. This paper will review a number of individual studies
      that addressed interactions of these metals/metalloids in both experimental and
      human exposure studies with particular emphasis on biomarkers. In general, co
      exposure to metal/metalloid mixtures produced more severe effects at both
      relatively high dose and low dose levels in a biomarker-specific manner. These
      effects were found to be mediated by dose, duration of exposure and genetic
      factors. While traditional endpoints, such as morphological changes and
      biochemical parameters for target organ toxicity, were effective measures for
      evaluating the toxicity of high dose metal/metalloid mixtures, biomarkers for
      oxidative stress, altered heme biosynthesis parameters, and stress proteins
      showed clear responses in evaluating toxicity of low dose metal/metalloid
      mixtures. Metallothionein, heat shock proteins, and glutathione are involved in
      regulating interactive effects of metal/metalloid mixtures at low dose levels.
      These findings suggest that further studies on interactions of these
      metal/metalloid mixtures utilizing biomarker endpoints are highly warranted.

PMID- 18325559
TI  - Effects of solubility of urban air fine and coarse particles on cytotoxic and
      inflammatory responses in RAW 264.7 macrophage cell line.
AB  - We investigated the inflammatory and cytotoxic activities of the water-soluble
      and -insoluble as well as organic-solvent-soluble and -insoluble fractions of
      urban air fine (PM(2.5-0.2)) and coarse (PM(10-2.5)) particulate samples. The
      samples were collected with a high volume cascade impactor (HVCI) in 7-week
      sampling campaigns of selected seasons in six European cities. Mouse macrophage
      cells (RAW 264.7) were exposed to the samples for 24 h. The production of nitric
      oxide (NO) and proinflammatory cytokines (TNFalpha, IL-6), and cytotoxicity (MTT
      test, apoptosis, cell cycle) were measured. The inflammatory and cytotoxic
      responses in both size ranges were mostly associated with the insoluble
      particulate fractions. However, both the water- and organic-solvent-soluble
      particulate fractions induced TNFalpha production and apoptosis and had some
      other cytotoxic effects. Soil-derived water-soluble and -insoluble components of
      the chemical PM(2.5-0.2) mass closure had consistent positive correlations with
      the responses, while the correlations were negative with the secondary inorganic
      anions (NO(3)(-), NH(4)(+), non-sea-salt SO(4)(2-)) and particulate organic
      matter (POM). With the PM(10-2.5) samples, sea salt and soluble soil components
      correlated positively with the induced toxic responses. In this size range, a
      possible underestimation of the insoluble, soil-related compounds containing Si
      and Ca, and biological components of POM, increased uncertainties in the
      evaluation of associations of the mass closure components with the responses. It
      is concluded that insoluble components of the complex urban air particulate
      mixture exert the highest inflammatory and cytotoxic activities in the macrophage
      cell line but, at the same time, they may operate as carriers for active water-
      and lipid-soluble components.

PMID- 18325560
TI  - Risk assessment in international operations.
AB  - During international peace-keeping missions, a diverse number of non-battle
      hazards may be encountered, which range from heavily polluted areas, endemic
      disease, toxic industrial materials, local violence, traffic, and even
      psychological factors. Hence, elevated risk levels from a variety of sources are
      encountered during deployments. With the emphasis within the Swedish military
      moving from national defense towards prioritization of international missions in
      atypical environments, the risk of health consequences, including long term
      health effects, has received greater consideration. The Swedish military is
      interested in designing an optimal approach for assessment of health threats
      during deployments. The Medical Intelligence group at FOI CBRN Security and
      Defence in Umea has, on request from and in collaboration with the Swedish Armed
      Forces, reviewed a variety of international health threat and risk assessment
      models for military operations. Application of risk assessment methods used in
      different phases of military operations will be reviewed. An overview of
      different international approaches used in operational risk management (ORM) will
      be presented as well as a discussion of the specific needs and constraints for
      health risk assessment in military operations. This work highlights the specific
      challenges of risk assessment that are unique to the deployment setting such as
      the assessment of exposures to a variety of diverse hazards concurrently.

PMID- 18325561
TI  - Spatially resolved ultrasonic attenuation in resistance spot welds: implications
      for nondestructive testing.
AB  - Spatial variation of ultrasonic attenuation and velocity has been measured in
      plane parallel specimens extracted from resistance spot welds. In a strong weld,
      attenuation is larger in the nugget than in the parent material, and the region
      of increased attenuation is surrounded by a ring of decreased attenuation. In the
      center of a stick weld, attenuation is even larger than in a strong weld, and the
      low-attenuation ring is absent. These spatial variations are interpreted in terms
      of differences in grain size and martensite formation. Measured frequency
      dependences indicate the presence of an additional attenuation mechanism besides
      grain scattering. The observed attenuations do not vary as commonly presumed with
      weld quality, suggesting that the common practice of using ultrasonic attenuation
      to indicate weld quality is not a reliable methodology.

PMID- 18325562
TI  - Evaluation of microbiological accumulation capability of the commercial sponge
      Spongia officinalis var. adriatica (Schmidt) (Porifera, Demospongiae).
AB  - This study was carried out to evaluate the microbiological accumulation
      capability of the demosponge Spongia officinalis var. adriatica. Six
      microbiological parameters were researched in two sampling periods in the water
      and in reared sponge samples coming from sites with different degrees of
      microbial contamination: an off-shore fish farm displaced off the Apulian coast
      (Southern Adriatic Sea) and a no-impacted area displaced into the Marine
      Protected Area of Porto Cesareo (Apulian coast-Ionian Sea). We detected the
      density of culturable heterotrophic bacteria by spread plate on marine agar,
      total culturable bacteria at 37 degrees C on Plate Count Agar and vibrios on
      thiosulphate-citrate-bile-sucrose-salt (TCBS) agar. Total and fecal coliforms as
      well as fecal streptococci concentrations were detected by the MPN method.
      Bacterial densities were always higher in the sponge homogenates compared with
      the corresponding seawater in the sampling points and in both sampling periods.
      As regard vibrios, total culturable bacteria at 37 degrees C and fecal
      streptococci concentrations, the highest values were observed in the sponge
      samples coming from the off-shore fish farm during the summer period. The ability
      of Spongia officinalis var. adriatica to accumulate the microbial pollution
      indicators suggests that this species can be employed as a bioindicator for
      monitoring water quality.

PMID- 18325563
TI  - 5-Enolpyruvylshikimate-3-phosphate synthase: determination of the protonation
      state of active site residues by the semiempirical method.
AB  - EPSP synthase (EPSPS) catalyzes the addition of shikimate-3-phosphate (S3P) and
      phosphoenolpyruvate (PEP) to form a tetrahedral intermediate (TI) that is
      converted to 5-enolpyruvylshikimate-3-phosphate (EPSP) and inorganic phosphate. A
      semiempirical molecular modeling study of the EPSPS active site containing the TI
      was implemented for the assignment of the protonation states of four basic
      residues, Lys22, Lys340, His385, and Lys411, based on the evaluation of 16
      different protonation states and comparison of the resulting energy minimized
      heavy atoms coordinates with available X-ray crystallographic data of the D313A
      mutant of EPSPS. The results, employing both gas phase and continuum solvent
      models, are indicative that after the TI formation the histidine residue is most
      probably in neutral form (N(epsilon)-protonated) and the lysine residues are in
      protonated form, which suggests that none of the presently proposed assignments
      of aminoacid residues involved in the reaction mechanism could be completely
      correct. The protonated state of Lys22 in the presence of the TI supports the
      proposal that this residue is a general acid catalyst for TI breakdown. Modeling
      of the native enzyme active site suggests that Asp313 residue has only minor
      effects on the definition of the TI position inside the active site. Hydrogen
      bonds distances suggest that, in order to act as a base, Asp313 needs the
      intermediacy of a hydroxyl group of the TI for effecting the attack on the TI
      methyl group in the elimination step leading to EPSP, as suggested previously in
      the literature.

PMID- 18325564
TI  - Distribution of pesticides and bisphenol A in sediments collected from rivers
      adjacent to coral reefs.
AB  - To investigate the deteriorating health of coral reefs in Okinawa, Japan, natural
      sediment samples were analyzed for diuron, Irgarol 1,051, chlorpyrifos, and
      bisphenol A (BPA) which are hazardous to corals. Samples were analyzed by solid
      phase extraction (SPE) followed by high-performance liquid chromatography with
      tandem mass spectrometry (LC-MS-MS). Although diuron and chlorpyrifos usage is
      only well recorded for farms and not for cities, these chemicals were detected in
      both rural and urban areas. Additionally, diuron concentration in urban areas was
      in some cases higher than in rural areas, which might be caused by greater
      consumption of these chemicals in home gardens in city areas. Irgarol 1051 was
      detected in downstream river areas, which are situated far from the source sites
      such as pier or fishery harbor (0.6-3.2 km). This result suggested that Irgarol
      1051 could be transported from the river mouths to the sampling sites during
      flood tides. High BPA concentrations were associated with urban areas (<1.2-22.0
      microg kg(-1)), while low concentrations were associated with rural areas (nd-6.8
      microg kg(-1)). The river sediments under study are delivered to coral reefs in
      large quantity through runoff caused by typhoons and other heavy rains. The
      highly hazardous chemicals are carried into coral reefs on these sediments.
      Therefore, these hazardous chemical substances may already be influencing the
      coral reefs.

PMID- 18325565
TI  - Composting and bioremediation process evaluation of wood waste materials
      generated from the construction and demolition industry.
AB  - The suitability of using bioremediation and composting techniques for diverting
      construction and demolition (C&D) waste from landfill has been validated in this
      study. Different timber products from C&D waste have been composted using various
      composting approaches. The present work demonstrates the quality of compost
      produced as a result of composting of mixed board product wood waste, which is
      frequently obtained from the construction and demolition industry. Three compost
      mixes were prepared by mixing shredded chip board, medium density fibre,
      hardboard and melamine. Poultry manure, Eco-Bio mixture and green waste were used
      as nutrient supplements. The results revealed that compost produced from mixtures
      of poultry manure and green waste used as nutrient supplements improved the
      performance in plant growth trials (phytotoxicity tests). Results obtained from
      the experimental study clearly indicate that the composts produced comply with
      the criterion suggested in BSI PAS 100 (A specification for compost materials)
      for use in different applications. Composting can also be demonstrated to be a
      very practical approach to material management including transport reduction to
      and from the site. The economic suitability of the process will be improved with
      the increase in landfill tax. In the current regulatory scenario, it is
      recommended that these materials should be composted at a centralised facility.

PMID- 18325566
TI  - Influence of iron plaque on uptake and accumulation of Cd by rice (Oryza sativa
      L.) seedlings grown in soil.
AB  - Iron plaque is ubiquitously formed on the root surfaces of rice. However, little
      is known about the role of iron plaque in Cd movement from soil to the plant
      aboveground parts. A pot experiment was conducted to investigate the influence of
      iron plaque in Cd uptake and accumulation by rice seedlings in soil. Rice
      seedlings were pre-cultivated in solution culture for 16 days. Two seedlings were
      transplanted in a nylon bag containing no substrate but surrounded by soil
      amended with Fe and Cd combined at rates of 0, 1, or 2 g Fe kg(-1) and 0, 2.0, or
      10 mg Cd kg(-1) soil. Fe was added to induce different amounts of iron plaque,
      and Cd to simulate Cd-polluted soils. Plants were grown for a further 43 days and
      then harvested. The length of the longest leaf and SPAD values of the newly
      mature leaves were measured during plant growth. Fe and Cd concentrations were
      determined in dithionite-citrate-bicarbonate (DCB) soil extracts and in plant
      roots and shoots. Shoot and root dry weights were significantly affected by Fe
      supply level but not by added Cd. Root dry weight declined with increasing Fe
      supply but shoot dry weight decreased at 2 g Fe kg(-1) and increased at 1 g Fe
      kg(-1) (except at 2 mg Cd kg(-1)). The length of the longest leaf and SPAD values
      of the newly mature leaves were significantly affected by plant growth stage and
      added Fe and Cd. Fe tended to diminish the negative effect of Cd on these two
      parameters. Cd concentrations in DCB extracts increased with increasing Cd and Fe
      supply. In contrast, external Fe supply markedly reduced shoot and root Cd
      concentrations and there was generally no significant difference between the two
      Fe supply levels. Shoot and root Cd concentrations increased with increasing Cd
      addition. Root Cd concentrations were negatively correlated with root Fe
      concentrations. The proportion of Cd in DCB extracts was significantly lower than
      in roots or shoots. The results indicate that enhanced Fe uptake by plants can
      diminish the negative effects of Cd to some extent and that iron plaque on root
      surfaces is of little significance in affecting uptake and accumulation of Cd by
      rice plants.

PMID- 18325567
TI  - Pesticides measured in air and precipitation in the Yamaska Basin (Quebec):
      occurrence and concentrations in 2004.
AB  - Air and precipitation samples were collected and analyzed for 91 pesticides or
      metabolites from May to September 2004 at St. Damase, an agricultural site
      located in Yamaska basin in Quebec, Canada. A broad range of pesticides was
      detected during this experiment where 40 different compounds were measured. Most
      of the samples showed more than 10 simultaneous pesticide detections and
      sometimes reaching 19 simultaneous detections. The most detected pesticides in
      air were trifluralin, metolachlor and captan, which were found in all the samples
      during the 5 months of measurements. For the detected compounds, the average
      concentrations ranged from 4 pg/m3 to 8 ng/m3. Some of the pesticides detected in
      air were found in precipitation samples as well showing that wet deposition can
      occur and have an impact on aquatic ecosystems. The most important pesticides
      detected were related to corn and soya cultivations, the two main cultures in
      this region highlighting that the major sources come from local applications. On
      the other hand, the detection of some pesticides in precipitation which were
      undetectable in air implies that some compounds may have a long range transport
      origin.

PMID- 18325568
TI  - Antidepressant-like effect of asiaticoside in mice.
AB  - In the present study, the potential antidepressant properties of asiaticoside
      were investigated in male mice in three tests -- splash test in the unpredictable
      chronic mild stress (CMS) model, tail suspension test (TST), forced swimming test
      (FST) -- with clomipramine being a positive control. In the splash test,
      asiaticoside (10 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly
      augmented the frequency of grooming behavior in stressed mice. In the tail
      suspension test, asiaticoside (10, 20 mg/kg, PO) and clomipramine (50 mg/kg, PO)
      significantly decreased immobility time. In the forced swimming test,
      asiaticoside (10, 20 mg/kg, PO) and clomipramine (50 mg/kg, PO) significantly
      decreased immobility time. These results suggest that asiaticoside may have
      antidepressant-like action.

PMID- 18325569
TI  - Outcome and safety of double-blind, placebo-controlled food challenges in 111
      patients sensitized to lipid transfer proteins.

PMID- 18325571
TI  - Effective prevention and therapy of experimental allergic asthma using a GATA-3
      specific DNAzyme.
AB  - BACKGROUND: Allergic bronchial asthma is a chronic inflammatory disease of the
      airways. The transcription factor GATA-3 was shown to play an important role in
      TH2 cell activation, but also in the regulation of other cell types involved in
      bronchial asthma including mast cells, eosinophils, and epithelial cells.
      DNAzymes represent a new class of antisense molecules that combines the
      specificity of DNA base pairing with an inherent RNA-cleaving enzymatic activity.
      OBJECTIVE: To develop a GATA-3 mRNA-specific DNAzyme and analyze its allergy
      preventing activity in murine models of experimental allergic asthma. METHODS:
      The most active DNAzyme (termed gd21) was selected by in vitro cleavage assays.
      Allergic airway inflammation was assessed by inflammatory cell and cytokine
      analysis within bronchoalveolar lavage. Lung histology, including goblet cell
      hyperplasia and lung function, was analyzed using head-out body-plethysmography.
      RESULTS: Intranasal administration of gd21 prevented airway inflammation and
      mucus production and inhibited development of airway hyperresponsiveness to
      methacholine in models of acute allergic airway inflammation. Similar effects
      were also detected in a model of chronic experimental asthma. Interestingly, gd21
      was at least as effective as other antisense molecules, and off-target effects
      were not detected. Further experiments indicated that pulmonary surfactant may
      facilitate the cellular uptake of gd21 by acting as an endogenous transfectant.
      CONCLUSION: These results indicate that topical application of the GATA-3
      specific DNAzyme is a promising novel approach for the treatment of allergic
      bronchial asthma.

PMID- 18325573
TI  - The burden of disease associated with filaggrin mutations: a population-based,
      longitudinal birth cohort study.
AB  - BACKGROUND: Atopic disease is a major health problem. Mutations in the filaggrin
      gene (FLG) confer major susceptibility to eczema and related asthma. OBJECTIVE:
      We sought to determine the natural history and burden of atopic disease conferred
      by the 2 most common FLG mutations in a large, population-based birth cohort
      study. METHODS: We analyzed the effect of the most common null alleles (R501X and
      2282del4) on several atopic phenotypes in a cohort of approximately 7000 English
      children born in 1990-1991. RESULTS: FLG null alleles associated strongly with
      eczema; eczema associated with these mutations presents in early life and is more
      persistent (hazard ratio for eczema resolution for those with FLG mutations to
      FLG wild type, 0.67; 95% CI, 0.58-0.77; P = 5 x 10(-8)). FLG mutations conferred
      a population asthma risk of 1.80 (95% CI, 1.34-2.41; P = .00019); asthma risk was
      especially high in the context of eczema (odds ratio, 3.16; 95% CI, 2.25-4.43; P
      = 1.4 x 10(-11)). Strong associations were identified with sensitization to
      grass, house dust mite, and cat dander and sensitization to multiple allergens
      (odds ratio, 2.12; 95% CI, 1.03-4.37; P = 5.42 x 10(-27)). CONCLUSION: FLG
      mutations are strong genetic determinants of eczema, early wheeze, asthma in the
      context of eczema, and atopic sensitization. They confer risk of a particular
      trajectory for eczema, with increased duration of disease and greater risk of
      asthma and multiple allergic sensitizations. FLG alleles help define the risk
      profile of children with eczema and help define the "eczema plus early wheeze"
      and "eczema plus asthma" phenotypes.

PMID- 18325574
TI  - Extrapolating evidence beyond age groups.

PMID- 18325575
TI  - Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to
      foods, drugs, and insects in 2007.
AB  - This review highlights some of the research advances in allergic skin disease,
      anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects that
      were reported primarily in the Journal in 2007. Advances in diagnosis include
      possible biomarkers for anaphylaxis, improved understanding of the relevance of
      food-specific serum IgE tests, identification of possibly discriminatory T-cell
      responses for drug allergy, and an elucidation of irritant responses for vaccine
      allergy diagnostic skin tests. Mechanistic studies are discerning T-cell and
      cytokine responses central to eosinophilic gastroenteropathies and food allergy,
      including the identification of multiple potential therapeutic targets. Regarding
      treatment, clinical studies of oral immunotherapy and allergen vaccination
      strategies show promise, whereas several clinical studies raise questions about
      whether oral allergen avoidance reduces atopic risks and whether probiotics can
      prevent or treat atopic disease. The importance of skin barrier dysfunction has
      been highlighted in the pathogenesis of atopic dermatitis (AD), particularly as
      it relates to allergen sensitization and eczema severity. Research has also
      continued to identify immunologic defects that contribute to the propensity of
      patients with AD to have viral and bacterial infections. New therapeutic
      approaches to AD, urticaria, and angioedema have been reported, including use of
      sublingual immunotherapy, anti-IgE, and a kallikrein inhibitor.

PMID- 18325576
TI  - Dermatologic adverse reactions to 7 common food additives in patients with
      allergic diseases: a double-blind, placebo-controlled study.

PMID- 18325577
TI  - Chimerism, point mutation, and truncation dramatically transformed mast cell
      delta-tryptases during primate evolution.
AB  - BACKGROUND: Tryptases are serine peptidases stored in mast cell granules. Rodents
      express 2 soluble tryptases, mast cell proteases (MCPs) 6 and 7. Human alpha- and
      beta-tryptases are orthologs of MCP-6. However, much of the ancestral MCP-7
      ortholog was replaced by parts of other tryptases, creating chimeric delta
      tryptase. Human delta-tryptase's limited activity is hypothesized to be due to
      truncation and processing mutations. OBJECTIVE: We sought to probe the origins
      and consequences of mutations in primate delta-tryptases. METHODS: Prosimian
      (lemur), monkey (macaque), great ape (orangutan, gorilla, and chimpanzee), and
      human delta-tryptase genes were identified by means of data mining and genomic
      sequencing. Resulting genes were analyzed phylogenetically and structurally.
      RESULTS: The seminal conversion event generating the delta-tryptase chimera
      occurred early because all primates studied contain delta-tryptase genes.
      Truncation, resulting from a nonsense mutation of Trp206, occurred much later,
      after orangutans and other great apes last shared an ancestor. The Arg-3Gln
      propeptide mutation occurred most recently, being present in humans and
      chimpanzees but not in other primates. Surprisingly, the major active tryptase in
      monkeys is full-length delta-tryptase, not beta-tryptase, which is the main
      active tryptase in human subjects. Models of macaque delta-tryptase reveal that
      the segment truncated in human subjects contains antiparallel beta-strands
      coursing through the substrate-binding cleft, accounting for truncation's drastic
      effect on activity. CONCLUSIONS: Transformations in the ancestral MCP-7-like gene
      during primate evolution caused dramatic variations in function. Although delta
      tryptases are nearly inactive in humans, they are active and dominant in monkeys.

PMID- 18325578
TI  - Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1
      immunity: role of dendritic cells.
AB  - BACKGROUND: The decrease in cellular immunity with aging is of considerable
      public health importance. Recent studies suggest that the redox equilibrium of
      dendritic cells (DCs) is a key factor in maintaining protective cellular immunity
      and that a disturbance of this homeostatic mechanism could contribute to immune
      senescence. OBJECTIVES: We sought (1) to elucidate the role of DC redox
      equilibrium in the decrease of contact hypersensitivity (CHS) and T(H)1 immunity
      during aging and (2) to determine how restoration of glutathione (GSH) levels by
      the Nrf2-mediated antioxidant defense pathway affects this decrease. METHODS: We
      assessed the effect of Nrf2 deficiency and boosting of GSH levels by the Nrf2
      agonist sulforaphane or the thiol precursor N-acetyl cysteine (NAC) on the CHS
      response to contact antigens in old mice. We studied the effect of SFN and NAC on
      restoring T(H)1 immunity by treating DCs ex vivo before adoptive transfer and in
      vivo challenge. RESULTS: Aging was associated with a decreased CHS response that
      was accentuated by Nrf2 deficiency. Systemic SFN treatment reversed this decrease
      through Nrf2-mediated antioxidant enzyme expression and GSH synthesis. Adoptive
      transfer of DCs from old animals induced a weakened CHS response in recipient
      animals. Treatment of DCs from old animals with SFN or NAC ex vivo restored the
      in vivo challenge response. CONCLUSION: SFN and NAC upregulate T(H)1 immunity in
      aging through a restoration of redox equilibrium.

PMID- 18325579
TI  - A comparison of skin prick tests, intradermal skin tests, and specific IgE in the
      diagnosis of mouse allergy.
AB  - BACKGROUND: Mouse sensitization is assessed by using skin testing and serum
      levels of mouse allergen-specific IgE (m-IgE). However, it is unknown whether a
      positive skin test response or m-IgE result accurately identifies those with
      clinically relevant mouse sensitization. OBJECTIVE: We sought to compare skin
      testing and m-IgE measurement in the diagnosis of mouse allergy. METHODS: Sixty
      nine mouse laboratory workers underwent skin prick tests (SPTs), intradermal
      tests (IDTs), and serum IgE measurements to mouse allergen, followed by nasal
      challenge to increasing concentrations of mouse allergen. Challenge response was
      assessed by nasal symptom score. RESULTS: Thirty-eight women and 31 men with a
      mean age of 30 years were studied. Forty-nine workers reported mouse-related
      symptoms, of whom 10 had positive m-IgE results and 12 had positive SPT
      responses. Fifteen had negative SPT responses but positive IDT responses.
      Positive nasal challenges were observed in 70% of workers with positive m-IgE
      results, 83% of workers with positive SPT responses, 33% of workers with negative
      SPT responses/positive IDT responses, and 0% of workers with negative IDT
      responses. SPTs performed best, having the highest positive and negative
      predictive values. Among participants with a positive challenge result, those
      with a positive SPT response or m-IgE result had a significantly lower challenge
      threshold than those with a positive IDT response (P = .01). Workers with a
      positive challenge result were more likely to have an increase in nasal
      eosinophilia after the challenge compared with those with a negative challenge
      result (P = .03). CONCLUSIONS: SPTs perform best in discriminating patients with
      and without mouse allergy. Mouse-specific IgE and IDTs appear to be less useful
      than SPTs in the diagnosis of mouse allergy.

PMID- 18325580
TI  - The 24-h distribution of falls and person-hours of physical activity in the home
      are strongly associated among community-dwelling older persons.
AB  - OBJECTIVES: Most research on falls among older persons focuses on health-related
      factors that affect the ability to maintain balance. The objective of the study
      is to determine the association between physical activity and occurrence of falls
      among community-dwelling older persons. METHODS: The distribution of falls and
      person-hours of physical activity in the home over 24 h was compared. The falls
      data (n=501) were extracted from a pooled dataset of three follow-up studies
      conducted between 1994 and 2005 (n=3587). The 1995 Dutch National Time-Budget
      Survey provided hour-by-hour information on activities performed by older
      individuals (n=459) in the home; this sample was representative for the
      Netherlands. The association between the 24-h distribution of falls and physical
      activity and the risk of falling (the ratio between the distribution of falls and
      physical activity) were determined. Participants were community-dwelling older
      persons aged 65 years and older. RESULTS: More physical activity was positively
      associated with more falls (Spearman correlation=.89, p<.000). The risk of
      falling at night (1 a.m.-6 a.m.) was almost eight times higher compared to 7 a.m.
      12 p.m. CONCLUSIONS: Physical activity is strongly associated with the number of
      falls in the home, measured over 24 h. Older persons may be at increased risk of
      falling if they are encouraged to become more physically active, or if they often
      get out of bed at night. Thus in addition to health-related factors, changes in
      level of physical activity should also be taken into account when estimating a
      person's risk of falling.

PMID- 18325581
TI  - Speech and language functions that require a functioning Broca's area.
AB  - A number of previous studies have indicated that Broca's area has an important
      role in understanding and producing syntactically complex sentences and other
      language functions. If Broca's area is critical for these functions, then either
      infarction of Broca's area or temporary hypoperfusion within this region should
      cause impairment of these functions, at least while the neural tissue is
      dysfunctional. The opportunity to identify the language functions that depend on
      Broca's area in a particular individual was provided by a patient with hyperacute
      stroke who showed selective hypoperfusion, with minimal infarct, in Broca's area,
      and acutely impaired production of grammatical sentences, comprehension of
      semantically reversible (but not non-reversible) sentences, spelling, and motor
      planning of speech articulation. When blood flow was restored to Broca's area, as
      demonstrated by repeat perfusion weighted imaging, he showed immediate recovery
      of these language functions. The identification of language functions that were
      impaired when Broca's area was dysfunctional (due to low blood flow) and
      recovered when Broca's area was functional again, provides evidence for the
      critical role of Broca's area in these language functions, at least in this
      individual.

PMID- 18325582
TI  - The Stroop effect in kana and kanji scripts in native Japanese speakers: an fMRI
      study.
AB  - Prior research has shown that the two writing systems of the Japanese orthography
      are processed differently: kana (syllabic symbols) are processed like other
      phonetic languages such as English, while kanji (a logographic writing system)
      are processed like other logographic languages such as Chinese. Previous work
      done with the Stroop task in Japanese has shown that these differences in
      processing strategies create differences in Stroop effects. This study
      investigated the Stroop effect in kana and kanji using functional magnetic
      resonance imaging (fMRI) to examine the similarities and differences in brain
      processing between logographic and phonetic languages. Nine native Japanese
      speakers performed the Stroop task in both kana and kanji scripts during fMRI.
      Both scripts individually produced significant Stroop effects as measured by the
      behavioral reaction time data. The imaging data for both scripts showed brain
      activation in the anterior cingulate gyrus, an area involved in inhibiting
      automatic processing. Though behavioral data showed no significant differences
      between the Stroop effects in kana and kanji, there were differential areas of
      activation in fMRI found for each writing system. In fMRI, the Stroop task
      activated an area in the left inferior parietal lobule during the kana task and
      the left inferior frontal gyrus during the kanji task. The results of the present
      study suggest that the Stroop task in Japanese kana and kanji elicits
      differential activation in brain regions involved in conflict detection and
      resolution for syllabic and logographic writing systems.

PMID- 18325583
TI  - Influence of photoinitiator type on the rate of polymerization, degree of
      conversion, hardness and yellowing of dental resin composites.
AB  - OBJECTIVES: To evaluate the degree of conversion (DC), maximum rate of
      polymerization (Rpmax), Knoop hardness (KHN) and yellowing (b-value) of resin
      composites formulated with phenylpropanedione (PPD), camphorquinone (CQ), or
      CQ/PPD at different concentrations. The hypotheses tested were (i) PPD or CQ/PPD
      would produce less Rpmax and yellowing than CQ alone without affecting DC and
      KHN, and (ii) Rpmax, DC, and KHN would be directly related to the absorbed power
      density (PDabs). METHODS: CQ/amine, PPD/amine and CQ/PPD/amine were used at low,
      intermediate and high concentrations in experimental composites. Photoinitiator
      absorption and halogen-light emission were measured using a spectrophotometer, Rp
      with differential scanning calorimetry (DSC), DC with DSC and FTIR, KHN with
      Knoop indentation; and color with a chromameter. The results were analyzed with
      two-way analysis of variance (ANOVA)/Student-Newman-Keul's test (p<0.05).
      Correlation tests were carried out between PDabs and each of DC, Rpmax and KHN.
      RESULTS: The PDabs increased with photoinitiator concentration and PPD samples
      had the lowest values. In general, maximum DC was comparable at intermediate
      concentration, while Rpmax and KHN required higher concentrations. DC was similar
      for all photoinitiators, but Rpmax was lower with PPD and CQ/PPD. PPD produced
      the lowest KHN. Yellowing increased with photoinitiator concentration. PPD did
      not reduce yellowing at intermediate and/or high concentrations, compared to CQ
      formulations. PDabs showed significant correlations with DC, Rpmax and KHN.
      CONCLUSION: PPD or CQ/PPD reduced Rpmax in experimental composites without
      affecting the DC. The use of PPD did not reduce yellowing, but reduced KHN. DC,
      Rpmax and KHN were dependent on PDabs.

PMID- 18325584
TI  - Response of coastal marine eco-environment to river fluxes into the sea: a case
      study of the Huanghe (Yellow) River mouth and adjacent waters.
AB  - The impact of the Huanghe (Yellow) River outflows on its estuary was investigated
      with river gauging and shipboard hydrographic observations. The river flux has
      been decreasing dramatically; the discharges of water and sediment in the 1990s
      dropped to 27.4% and 31.9% of those in the 1950s, respectively, resulting in
      frequent and lengthy events of downstream channel dry-up since the 1970s. There
      were accumulatively 897 zero-flow days during the 1990s in the river course below
      the Lijin Hydrological Station, 100 km upstream from the river mouth, which is
      82.4% of that in 1972. As freshwater input decreases, river-borne nutrients to
      the estuarine increased significantly. Concentration of dissolved inorganic
      nitrogen (DIN) in the 1990s was four times of that in 1950s. Changes in amount
      and content of the riverine inputs have greatly affected the estuarine ecosystem.
      Over the past several decades, sea surface temperature and salinity in the
      estuary and its adjacent waters increased and their distribution pattern altered
      in response to the reduction of freshwater inflow. The distribution of and
      seasonal succession in nutrient concentrations in the surface layer have also
      changed with a shift of river outlet and the decrease in riverine nutrient loads.
      Furthermore, deterioration of estuarine ecosystem by less river input has
      decreased primary productivity in the deltaic region waters, and in turn
      depressed the fishery.

PMID- 18325585
TI  - Characterization and optimization of RGD-containing silk blends to support
      osteoblastic differentiation.
AB  - The effect of blending two silk proteins, regenerated Bombyx mori fibroin and
      synthetic spidroin containing RGD, on silk film material structure (beta-sheet
      content) and properties (solubility), as well as on biological response
      (osteoblast adhesion, proliferation and differentiation) was investigated.
      Although the elasticity and strength of silks make them attractive candidates for
      bone, ligament, and cartilage tissue engineering applications, silk proteins
      generally lack bioactive peptides for enhancing cell functions. Thus, a synthetic
      spider silk, spidroin, containing two RGD cell adhesive sequences (RGD-spidroin)
      was engineered. RGD-spidroin was blended with different ratios of fibroin and
      spun coat into films on glass coverslips. beta-Sheet formation, contact angle,
      surface topography and RGD surface presentation were characterized and correlated
      with cell behavior. We found that the amount of beta-sheet formation was directly
      related to the RGD-spidroin content of the blends after annealing, with the pure
      RGD-spidroin demonstrating the highest amount of beta-sheet content. The
      increased beta-sheet content improved film stability under culture conditions. A
      new visualization technique demonstrated that the RGD presentation on the film
      surface was affected by both the RGD-spidroin content and annealing conditions.
      It was determined that 10mass% RGD-spidroin was necessary to improve film
      stability and to achieve osteoblast attachment and differentiation.

PMID- 18325586
TI  - The thrombogenicity of human umbilical vein endothelial cell seeded collagen
      modules.
AB  - Modular tissue-engineered constructs are assembled from sub-mm sized cylindrical
      collagen gel modules which are covered with a surface layer of human umbilical
      vein endothelial cells (HUVEC). The resulting construct is permeated by a network
      of interconnected endothelial cell lined channels to facilitate blood perfusion
      and nutrient delivery. This design strategy relies critically on the endothelial
      cells' layer behaving in a non-thrombogenic manner on the module surface and the
      objective here was to characterize this thrombogenicity. HUVEC prolonged clotting
      times in whole blood-module mixtures, and enabled slightly heparinized whole
      blood perfusion of an assembled modular construct in vitro with no increase in
      platelet loss compared to background levels. Flow cytometry and scanning electron
      microscopy indicated that HUVEC seeded modules reduced platelet activation and
      deposition but not leukocyte activation, compared to collagen only modules.
      Plasma recalcification times on non-stimulated HUVEC were longer compared to
      stimulated HUVEC but not different than that on collagen only module films and
      were not prolonged by incubation with a tissue factor blocking antibody. Together
      these data suggest that a functional non-thrombogenic layer of EC was generated
      on the module surface and that this layer should be sufficient to maintain
      continuous blood flow through an engineered modular tissue. In/ex vivo studies
      are warranted to confirm this conclusion.

PMID- 18325587
TI  - Lipopolysaccharide induces apoptosis in Carassius auratus lymphocytes, a possible
      role in pathogenesis of bacterial infection in fish.
AB  - Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria, is capable of
      eliciting a wide variety of pathophysiological effects, including endotoxin
      shock, tissue injury and lethality in both humans and animals. It is also a
      potent stimulant to initiate the proliferation, differentiation and activation of
      B lymphocytes and macrophages, resulting in changes of inflammatory cytokines,
      such as TNF-alpha, IL1-beta, IL6, IL-8 and IL-12, and enhancement of immune
      responses. However, little is known about its effect on the induction of
      apoptosis in lymphocytes. In the present study, the lymphocytes from Carassius
      auratus were employed for this purpose. The cells were exposed to LPS at various
      doses for different time periods. By careful apoptotic characteristic analysis,
      such as condensation of nuclear chromatin, fragmentation of genomic DNA and
      formation of apoptotic bodies, it provided the first evidence that LPS had
      apoptotic-inducing effect on fish lymphocytes in a time- and dose-dependent
      manner. LPS exposure induced significant increase of intracellular reactive
      oxygen species (ROS), loss of mitochondrial transmembrane potential (DeltaPsi),
      depletion of ATP production, down-regulation of Bcl-2 expression, up-regulation
      of Bax and mitochondrial NO-synthase (mNOS) expression, and selective activation
      of caspase-9 rather than caspase-8. Each of these observations suggests that the
      LPS-induced apoptosis in C. auratus lymphocytes occurs largely via the
      mitochondrial apoptotic pathway. This observation was different from the
      mechanism behind the LPS-induced apoptosis in mammalian macrophages/thymocytes
      that occurs via the TNF-alpha-mediated death-receptor pathway. Our study
      suggested the existence of a possible novel role in the pathogenesis of Gram
      negative bacterial infection in fish and even in mammals, which may contribute to
      the therapy of bacterial diseases. Also, it will help to gain more insights into
      the mechanisms of septic shock and of LPS-induced immunosuppression and
      autoimmunity.

PMID- 18325588
TI  - Functional genomic analysis of the response of Atlantic cod (Gadus morhua) spleen
      to the viral mimic polyriboinosinic polyribocytidylic acid (pIC).
AB  - In order to improve our understanding of how Atlantic cod (Gadus morhua) respond
      to viruses, we characterized immune-related gene expression in spleen tissues
      following stimulation with a synthetic double-stranded RNA polyriboinosinic
      polyribocytidylic acid (pIC). We used reciprocal suppression subtractive
      hybridization (SSH) cDNA libraries and quantitative RTPCR (QPCR) to identify and
      quantify pIC-responsive transcripts. A total of 3874 expressed sequence tags
      (ESTs) were generated from SSH libraries enriched for genes responsive to pIC.
      Thirteen immune-relevant genes from the libraries were subjected to QPCR. Genes
      confirmed as up-regulated by pIC included interferon stimulated gene 15, a small
      inducible cytokine, interferon regulatory factors (1, 7, and 10), MHC class I,
      viperin, and ATP-dependent helicase LGP2. Alpha-1-microglobulin (bikunin) was
      down-regulated, suggesting that pIC may suppress the acute phase response. Since
      the SSH libraries built for this study identified genes involved in the antiviral
      response, they are important resources for studying the responses of Atlantic cod
      to viruses. Evidence is provided for the existence of a RIG-I-like RNA helicase
      viral recognition pathway in Atlantic cod. Taken together, our data show that
      Atlantic cod can recognize double-stranded RNA and mount a rapid and potent
      interferon pathway response that is similar to that observed in other fish
      species and higher vertebrates.

PMID- 18325589
TI  - Sexually disrupting effects of nonylphenol and diethylstilbestrol on male silver
      carp (Carassius auratus) in aquatic microcosms.
AB  - Based on detected nonylphenol (NP) levels in aquaculture water, this study
      investigated sexually disrupting effects in mature male silver carp (Carassius
      auratus) exposed to NP and a positive control diethylstilbestrol (DES). The
      combined evidences of steroid hormone (17beta-estradiol, estrone and
      testosterone) levels and hispathological pictures showed that NP (10 microg/L)
      and DES could exert estrogenic effects through indirect mechanisms [i.e.
      increased estrogens levels (up to two times) and decreased androgen level in
      serum (down to 20-30%)], which might subsequently induce vitellogenin synthesis
      in liver. Environmental realistic concentrations of NP might be on the verge of
      inducing significant estrogenic effects in male silver carps. High amounts of NP
      and DES might be accumulated in fish serum, and the uptake by fish was possibly
      responsible for their quick attenuation in experimental tank water. NP and DES
      might have different metabolic mechanisms, the estrogenic effects of DES were
      more significant than those of NP.

PMID- 18325590
TI  - Rhabdoid and papillary meningioma with leptomeningeal dissemination.
AB  - Rhabdoid meningioma is a rare variant of meningioma classified as grade III under
      the new World Health Organization (WHO) classification of brain tumors. Although
      this tumor is known for its aggressive behavior, dissemination into cerebral
      spinal fluid (CSF) is extremely rare. We report here a case of rhabdoid
      meningioma in a young man, operated on twice previously, who presented with
      multiple CSF areas of seeding in the brain and spinal cord. The imaging findings
      for this tumor, including diffusion and perfusion MR sequences, are highlighted.
      This particular histological subtype of meningioma has a poor prognosis and must
      be treated aggressively.

PMID- 18325591
TI  - Usefulness of diffusion-weighted imaging and the apparent diffusion coefficient
      in the assessment of head and neck tumors.
AB  - The aim of this review was to determine the usefulness of diffusion-weighted
      imaging (DWI) and the apparent diffusion coefficient (ADC) in the assessment of
      head and neck tumors. DWI and the ADC can help in the differential diagnosis of
      particular disorders (such as carcinomas vs lymphomas, or necrosis vs abscess) of
      the head and neck. The ADC can also provide further information to help
      differentiate benign from malignant tumors, as ADC values are usually lower in
      cases of malignancy. However, the ADC is itself influenced by various complex
      factors such as the cellularity and matrix of tumors and there is also some
      overlap between certain benign and malignant tumors of the salivary glands.

PMID- 18325592
TI  - Vaccination of larvae of the bony fish gilthead seabream reveals a lack of
      correlation between lymphocyte development and adaptive immunocompetence.
AB  - Fish eggs are released and embryos hatch into a pathogenically hostile
      environment, at a time when their immunological capacity is severely limited.
      Although the eggs are initially protected by the envelope as well as by several
      innate and adaptive immune substances, which are transferred to eggs during fish
      vitellogenesis, it seems that young specimens depend fundamentally on their
      innate defence mechanisms. Here we show in the gilthead seabream, an
      immunologically tractable teleost fish model, that the first lymphocyte marker
      genes, those coding for the two subunits for the recombination activating gene,
      were detected by RT-PCR around 21-27 days post-hatching (dph). In addition, the
      transcripts coding for the alpha and beta subunits of the T-cell receptor and the
      light and heavy chains of immunoglobulin M were detected at 27-48 dph. However,
      most innate immune genes analyzed were already expressed at hatching, including
      those coding for the toll-like receptors, pro- and anti-inflammatory molecules,
      antiviral and antibacterial factors, and phagocyte markers. Using the information
      from the gene expression study, we also examined the achievement of
      immunocompetence by analyzing the protection induced by a bacterin against the
      pathogenic bacterium Photobacterium damselae subsp. piscicida. The results show
      that vaccination of young larvae of this species by either immersion or oral
      routes resulted in increased susceptibility to infection of the specimens, and
      point to the lack of correlation between the achievement of immunocompetence and
      detection of the adaptive immunity markers.

PMID- 18325593
TI  - Slower rescue of ER homeostasis by the unfolded protein response pathway
      associated with common variable immunodeficiency.
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency
      characterized by hypogammaglobulinemia and recurrent infections. Herein we
      addressed the role of unfolded protein response (UPR) in the pathogenesis of the
      disease. Augmented unspliced X-box binding protein 1 (XBP-1) mRNA concurrent with
      co-localization of IgM and BiP/GRP78 were found in one CVID patient. At confocal
      microscopy analysis this patient's cells were enlarged and failed to present the
      typical surface distribution of IgM, which accumulated within an abnormally
      expanded endoplasmic reticulum. Sequencing did not reveal any mutation on XBP-1,
      neither on IRE-1alpha that could potentially prevent the splicing to occur.
      Analysis of spliced XBP-1, IRE-1alpha and BiP messages after LPS or Brefeldin A
      treatment showed that, unlike healthy controls that respond to these endoplasmic
      reticulum (ER) stressors by presenting waves of transcription of these three
      genes, this patient's cells presented lower rates of transcription, not reaching
      the same level of response of healthy subjects even after 48 h of ER stress.
      Treatment with DMSO rescued IgM and IgG secretion as well as the expression of
      spliced XBP-1. Our findings associate diminished splicing of XBP-1 mRNA with
      accumulation of IgM within the ER and lower rates of chaperone transcription,
      therefore providing a mechanism to explain the observed hypogammaglobulinemia.

PMID- 18325594
TI  - Pattern of expression of immune-relevant genes in the gonad of a teleost, the
      gilthead seabream (Sparus aurata L.).
AB  - Immune responses in the testis are regulated in a way that provides protection
      for the developing male germ cells, while permitting qualitatively normal
      inflammatory responses and protection against infection. In addition, germ cells
      are potent targets for the growth factors and cytokines which regulate the
      reproductive process. Our study analyzes for the first time the pattern of
      expression of several immune-relevant genes in the gonad of a seasonal breeding
      teleost fish. The immune molecules analyzed include (i) inflammatory molecules,
      such as interleukin-1b (il1b), il6, tumor necrosis factor-a (tnfa),
      cyclooxygenase-2 (cox2) and the NADPH oxidase subunit p40(phox) (ncf4 gene); (ii)
      the anti-inflammatory cytokine transforming growth factor-b1 (tgfb1) and its type
      2 receptor tgfbr2; (iii) innate immune receptors, including toll-like receptor 9
      (tlr9), tlr5, tlr22 and macrophage-colony stimulating factor receptor (mcsfr);
      (iv) lymphocyte receptors, such as the beta subunit of T-cell receptor (Tcrb) and
      the heavy chain of immunoglobulin M (ighm); (v) the anti-bacterial molecules
      lysozyme (lyz), hepcidin (hamp) and complement component 3 (c3); (vi) the anti
      viral molecule myxovirus (influenza) resistance protein (mx); and (vii) molecules
      related to leukocyte infiltration, including the CC chemokine ccl4, the CXC
      chemokine il8 and the leukocyte adhesion molecule E-selectin (Sele). Notably, all
      of them show a pattern of expression that depends on the reproductive stage of
      the first two reproductive cycles when the fish develop and function as males.
      Furthermore, we demonstrate that some of these immune-relevant molecules, such as
      Il1b and Mcsfr, are produced by germ cells (Il1b) and ovarian and testicular
      somatic cells (Mcsfr). These data suggest that, as occurs in mammals, there is a
      critical balance between immune molecules and that these may play an essential
      role in the orchestration of gametogenesis and the maintenance of gonad tissue
      homeostasis in fish.

PMID- 18325595
TI  - Is the Sciatic Functional Index always reliable and reproducible?
AB  - The Sciatic Functional Index (SFI) is a quite useful tool for the evaluation of
      functional recovery of the sciatic nerve of rats in a number of experimental
      injuries and treatments. Although it is an objective method, it depends on the
      examiner's ability to adequately recognize and mark the previously established
      footprint key points, which is an entirely subjective step, thus potentially
      interfering with the calculations according to the mathematical formulae proposed
      by different authors. Thus, an interpersonal evaluation of the reproducibility of
      an SFI computer-aided method was carried out here to study data variability. A
      severe crush injury was produced on a 5 mm-long segment of the right sciatic
      nerve of 20 Wistar rats (a 5000 g load directly applied for 10 min) and the SFI
      was measured by four different examiners (an experienced one and three newcomers)
      preoperatively and at weekly intervals from the 1st to the 8th postoperative
      week. Three measurements were made for each print and the average was calculated
      and used for statistical analysis. The results showed that interpersonal
      correlation was high (0.82) in the 3rd, 4th, 5th, 7th and 8th weeks, with an
      unexpected but significant (p<0.01) drop in the 6th week. There was virtually no
      interpersonal correlation (correlation index close to 0) on the 1st and 2nd
      weeks, a period during which the variability between animals and examiners
      (p=0.24 and 0.32, respectively) was similar, certainly due to a poor definition
      of the footprints. The authors conclude that the SFI method studied here is only
      reliable from the 3rd week on after a severe lesion of the sciatic nerve of rats.

PMID- 18325596
TI  - Evaluation of functional nerve recovery with Visual-SSI--a novel computerized
      approach for the assessment of the static sciatic index (SSI).
AB  - Complete nerve transection (neurotmesis) of the rat sciatic nerve is a well
      established animal model. The most frequently used behavioural for evaluation of
      neurotmesis-induced deficits is the walking track analysis with calculation of
      the sciatic functional index (SFI). More recently, the static sciatic index (SSI)
      has been developed, which shows a good correlation with the SFI. However, despite
      all advantages (high accessibility, easy handling, high accuracy, cost
      effectiveness), the SSI is still not widely used. We, therefore, developed a
      novel programme ("Visual-SSI"), which will be made freely available for the
      assessment of the SSI. As gold-standard for the treatment of neurotmesis-induced
      nerve gaps, autologous nerve transplantation studies in the rat sciatic nerve
      model (n=16 [6 weeks], n=8 [12 weeks]) were carried out to test the effectiveness
      and feasibility of the Visual-SSI software. We observed a significant recovery
      starting from the pre-operative condition over the 3rd, 6th, 9th weeks until the
      12th week after surgery (p<0.05). Theoretically, the SSI can be calculated from
      both rearing and normal standing position of the rats and we investigated whether
      the SSI is affected differentially by these positions. We observed no significant
      differences between animals in a rearing and normal standing stance (p>0.05). The
      present method combines efficiency (simplicity of use, rapid and economical
      setup) with accurate and precise quantification of the functional regeneration in
      the sciatic nerve lesion model of the rat.

PMID- 18325597
TI  - The vermicelli handling test: a simple quantitative measure of dexterous forepaw
      function in rats.
AB  - Loss of function in the hands occurs with many brain disorders, but there are few
      measures of skillful forepaw use in rats available to model these impairments
      that are both sensitive and simple to administer. Whishaw and Coles previously
      described the dexterous manner in which rats manipulate food items with their
      paws, including thin pieces of pasta [Whishaw IQ, Coles BL. Varieties of paw and
      digit movement during spontaneous food handling in rats: postures, bimanual
      coordination, preferences, and the effect of forelimb cortex lesions. Behav Brain
      Res 1996;77:135-48]. We set out to develop a measure of this food handling
      behavior that would be quantitative, easy to administer, sensitive to the effects
      of damage to sensory and motor systems of the CNS and useful for identifying the
      side of lateralized impairments. When rats handle 7 cm lengths of vermicelli,
      they manipulate the pasta by repeatedly adjusting the forepaw hold on the pasta
      piece. As operationally defined, these adjustments can be easily identified and
      counted by an experimenter without specialized equipment. After unilateral
      sensorimotor cortex (SMC) lesions, transient middle cerebral artery occlusion
      (MCAO) and striatal dopamine depleting (6-hydroxydopamine, 6-OHDA) lesions in
      adult rats, there were enduring reductions in adjustments made with the
      contralateral forepaw. Additional pasta handling characteristics distinguished
      between the lesion types. MCAO and 6-OHDA lesions increased the frequency of
      several identified atypical handling patterns. Severe dopamine depletion
      increased eating time and adjustments made with the ipsilateral forepaw. However,
      contralateral forepaw adjustment number most sensitively detected enduring
      impairments across lesion types. Because of its ease of administration and
      sensitivity to lateralized impairments in skilled forepaw use, this measure may
      be useful in rat models of upper extremity impairment.

PMID- 18325598
TI  - Hypomania: a depressive inhibition override defense mechanism.
AB  - OBJECTIVE: Evolutionary perspectives on bipolar disorders can further our
      understanding of the origins of these conditions, and assist clinicians in
      distinguishing normal from abnormal states. Hypomania is unique amongst bipolar
      conditions in that it seems to have beneficial aspects and can be difficult to
      diagnose, in contrast to full-blown mania and depression. A theoretical
      perspective regarding the evolution of hypomania as a defense mechanism is
      presented. METHOD: Literature review focused on the fitness reducing aspects of
      depression and the fitness enhancing aspects of hypomania/mania. RESULTS: Of all
      the adversity inherent in depression, inhibition of physical and mental activity
      depressive inhibition-has the most detrimental consequences, and throughout our
      evolution would have significantly reduced fitness. It is proposed that hypomania
      evolved as a depressive inhibition override defense mechanism, typically
      operating in a short-term time frame, to restore physical and mental activity to
      fitness sustaining or enhancing levels. Over-activity and not mood enhancement
      enabled hypomania to function as a defense mechanism against the fitness reducing
      state of depressive inhibition. Contributing to depressive inhibition are the
      Behavioral Activation System (BAS) and the Behavioral Inhibition System (BIS),
      two basic motivational systems. Depressive inhibition consists to some extent of
      low BAS and high BIS. As human intelligence evolved cognitions inhibiting BAS and
      activating BIS became amplified, resulting in intensified depressive inhibition.
      LIMITATIONS: A theoretical perspective. CONCLUSIONS: Given its ability to
      override depressive inhibition hypomania might be viewed as a natural treatment
      as opposed to a problem to treat, producing maximal improvement in areas where
      functioning has suffered the most while typically enhancing social behavior.

PMID- 18325599
TI  - C-reactive protein measurements in meat juice of pigs.
AB  - A time-resolved immunofluorometric assay was evaluated for measurement of C
      reactive protein in meat juice from diaphragmatic muscle collected from
      slaughtered pigs. Analytical and clinical validation of the method was performed
      by using meat juice samples, obtained by freezing and thawing muscle pieces. The
      intra- and inter-assay coefficients of variation ranged from 2.2-5.8% to 7.9
      14.3%, respectively. The limit of detection was 0.00038 microg/ml. The method
      measured the CRP concentrations in a linear manner with a good accuracy (r=0.99).
      CRP concentrations in serum were highly correlated with those in diaphragmatic
      meat juice (r=0.90; p<0.001). CRP concentrations were significantly higher in
      clinically affected pigs compared to non-diseased pigs. The assay described here
      provides a sensitive method for measuring CRP concentrations in meat juice, which
      can represent a suitable alternative to serum or blood samples and simplifies the
      process of sampling collection at slaughter.

PMID- 18325600
TI  - Altered cytokine levels in the blood and cerebrospinal fluid of chronic pain
      patients.
AB  - This study replicates and extends prior reports of abnormal cytokine levels in
      chronic pain patients and has correlated the alterations with pain severity. In
      addition, there appeared to be a need to directly assess cerebrospinal fluid
      (CSF) because previous findings on cytokine concentrations in peripheral
      circulation have been inconsistent. CSF and blood specimens were obtained from 14
      patients with distal painful non-diabetic polyneuropathy (DPPN) or post-traumatic
      neuralgia (PTN). Elevated receptor levels for Tumor Necrosis Factor (sTNFr) were
      the most distinctive abnormality along with low interleukin-10 (IL-10). sTNFr in
      CSF and blood, and IL-1ss in CSF, were positively associated with pain intensity,
      whereas IL-10 in both compartments was inversely correlated with pain symptoms.
      An imbalance of pro- and anti-inflammatory cytokines appears to be a clinically
      relevant feature, which may contribute to the maintenance of chronic pain.

PMID- 18325601
TI  - The effects of levobupivacaine versus levobupivacaine plus magnesium infiltration
      on postoperative analgesia and laryngospasm in pediatric tonsillectomy patients.
AB  - BACKGROUND: The aim of this study was to evaluate whether the addition of
      magnesium to levobupivacaine will decrease the postoperative analgesic
      requirement or not, and to investigate the possible preventive effects on
      laryngospasm. METHODS: Seventy-five children undergoing elective tonsillectomy
      and/or adenoidectomy surgery. The drug was prepared as only NaCl 0.9% for the
      first group (Group S, n=25), levobupivacaine 0.25% for the second group (Group L,
      n=25), and levobupivacaine 0.25% plus magnesium sulphate 2mg/kg for the third
      group (Group M, n=25). Pain was recorded at 15th minute, 1st, 4th, 8th, 16th, and
      24th hour postoperatively. Pain was evaluated using a modified Children's
      Hospital of Eastern Ontario pain scale (mCHEOPS). Incidence of postoperative
      nausea and vomiting (PONV) was assessed at various time intervals (0-2, 2-6, 6
      24h) by numeric rank score. Patients were followed for laryngospasm for 1h in
      recovery room after extubation. Other complications appeared within 24h
      postoperatively were recorded. RESULTS: All postoperative CHEOPS values were
      lower than control in both groups. Analgesic requirement was decreased
      significantly in both groups in comparison with control patients, but this
      requirement was significantly lower in Group M (p<0.05). Although laryngospasm
      was not observed in Group M, the difference between groups was not statistically
      significant. PONV was similar in both groups. CONCLUSIONS: Levobupivacaine and
      Levobupivacaine plus magnesium infiltration decrease the post-tonsillectomy
      analgesic requirement. Insignificant preventive effect of low doses of magnesium
      infiltration on laryngospasm observed in this study needs to be clarified by
      larger series.

PMID- 18325602
TI  - The prediction of hearing thresholds with auditory steady-state responses for
      cochlear implanted children.
AB  - OBJECTIVES: The objectives of this study were to investigate the efficacy of
      auditory steady-state response (ASSR) in predicting cochlear implanted children's
      actual behavioural thresholds at various frequencies. METHODS: Twenty-two
      children with cochlear implants (Nucleus 24 devices) participated in this study.
      Behavioural thresholds and/or ASSR in cochlear implanted children were obtained
      to determine the predictive accuracy rates and errors by comparing the estimated
      range of thresholds with the actual behavioural thresholds. RESULTS: Stable ASSR
      threshold results were obtained in 22 cochlear implanted children. The predictive
      accuracy rates were the highest and prediction errors were the smallest at 4000
      Hz, among the four tested frequencies, using either the Rance 1995 or the Rance
      2002 linear regression formulae. The Rance 2002 regression formulae had a higher
      predictive accuracy and fewer errors than the Rance 1995 regression formulae in
      predicting the hearing threshold of cochlear implanted patients at all tested
      frequencies. CONCLUSIONS: Both behavioural thresholds and ASSR thresholds
      revealed significant improvements after cochlear implantation. ASSR may be used
      as a tool in predicting hearing thresholds after cochlear implantation in
      children. The predictive accuracy is best at 4000 Hz with the Rance 2002 linear
      regression formulae.

PMID- 18325603
TI  - Recognition of paediatric otopathology by General Practitioners.
AB  - OBJECTIVE: General Practitioners (GPs) are required to diagnose a number of
      common ear pathologies on a regular basis. In particular, otitis media with
      effusion (OME) can be well managed in primary care if a reliable diagnosis can be
      made. We set out to assess the confidence and ability of GPs to diagnose
      otopathology, as well as the access that they had to tympanometry and pneumatic
      otoscopy to assist in making their diagnoses. METHODS: Twenty GPs were shown a
      series of forty slides, half with OME and half with normal tympanic membranes;
      they were then asked to state whether each image represented an ear with OME or
      not. The same GPs were then shown 20 slides, half of which were ears with a
      common pathology and half were normal; the participants were asked to state
      whether the slide was of a normal ear or make a diagnosis of the pathology.
      Access to equipment and previous training were assessed via a short
      questionnaire. RESULTS: The median score for the correct diagnosis of OME was 53%
      (range 30-67.5%), only slightly higher than chance. The participants correctly
      identified that an ear was abnormal for a mean of 80% of the time (range 65-95%),
      but were only able to make a correct diagnosis of the pathology for a mean of 41%
      of the ears (range 20-80%). No participant had access to pneumatic otoscopy or
      tympanometry in their practices. CONCLUSIONS: GPs have difficulty in correctly
      diagnosing OME from otoscopy alone, but are able to determine the presence of
      other otopathology. They were less able to diagnose specific abnormalities.

PMID- 18325604
TI  - Nasal mucus transportability in children with cleft palate.
AB  - OBJECTIVES: Children with cleft palate (CP) have a high prevalence of sinusitis.
      Considering that nasal mucus properties play a pivotal role in the upper airway
      defense mechanism, the aim of the study was to evaluate nasal mucus
      transportability and physical properties from children with CP. SETTING: Hospital
      for Rehabilitation of Craniofacial Anomalies, School of Dentistry, University of
      Sao Paulo, Bauru, SP, Brazil and Laboratory of Experimental Air Pollution, School
      of Medicine, University of Sao Paulo, Sao Paulo, SP, Brazil. METHODS: Nasal mucus
      samples were collected by nasal aspiration from children with CP and without CP
      (non-CP). Sneeze clearance (SC) was evaluated by the simulated sneeze machine. In
      vitro mucus transportability (MCT) by cilia was evaluated by the frog palate
      preparation. Mucus physical surface properties were assessed by measuring the
      contact angle (CA). Mucus rheology was determined by means of a magnetic
      rheometer, and the results were expressed as log G* (vectorial sum of viscosity
      and elasticity) and tan delta (relationship between viscosity and elasticity)
      measured at 1 and 100 rad/s. RESULTS: Mucus samples from children with CP had a
      higher SC than non-CP children (67+/-30 and 41+/-24 mm, respectively, p<0.05).
      Mucus samples from children with CP had a lower CA (24+/-16 degrees and 35+/-11
      degrees , p<0.05) and a higher tan delta 100 (0.79+/-0.24 and 0.51+/-0.12,
      p<0.05) than non-CP children. There were no significant differences in mucus MCT,
      log G* 1, tan delta 1 and log G* 100 obtained for CP and non-CP children.
      CONCLUSIONS: Nasal mucus physical properties from children with CP are associated
      with higher sneeze transportability. The high prevalence of sinusitis in children
      with CP cannot be explained by changes in mucus physical properties and
      transportability.

PMID- 18325605
TI  - Detection and isolation of H5N1 influenza virus from large volumes of natural
      water.
AB  - Various species of aquatic or wetlands birds can be the natural reservoir of
      avian influenza A viruses of all hemagglutinin (HA) subtypes. Shedding of the
      virus into water leads to transmission between waterfowl and is a major threat
      for epidemics in poultry and pandemics in humans. Concentrations of the influenza
      virus in natural water reservoirs are often too low to be detected by most
      methods. The procedure was designed to detect and isolate low concentrations of
      the influenza virus in large volumes of water without the need for costly
      installations and reagents. The virus was adsorbed onto formalin-fixed
      erythrocytes and subsequently isolated in chicken embryos. Sensitivity of the
      method was determined using a reverse-genetic H5N1 virus. A concentration as low
      as 0.03 of the 50% egg infection dose per milliliter (EID50/ml) of the initial
      volume of water was effectively detected. The probability of detection was
      approximately 13%, which is comparable to that of detecting the influenza virus M
      gene by PCR amplification. The method can be used by field workers, ecologists,
      ornithologists, and researchers who need a simple method to isolate H5N1
      influenza virus from natural reservoirs. The detection and isolation of virus in
      embryonated chicken eggs may help epidemiologic, genetic, and vaccine studies.

PMID- 18325606
TI  - Penciclovir is a potent inhibitor of feline herpesvirus-1 with susceptibility
      determined at the level of virus-encoded thymidine kinase.
AB  - Feline herpesvirus-1 (FHV-1) is the causative agent of a severe ocular disease in
      cats for which a safe potent antiviral chemotherapeutic agent is highly demanded.
      The sensitivity of FHV-1 to inhibition by three anti-herpetic nucleoside
      analogues [acyclovir (ACV), penciclovir (PCV) and cidofovir (CDV)] was tested by
      means of yield reduction assay. ACV showed very poor ability to inhibit FHV-1
      replication. At low multiplicity of infection (MOI), both PCV and CDV were nearly
      equally effective with IC50 values ranging between 6 and 8 microg/ml. However,
      when the MOI was raised to 3PFU/cell, the activity of CDV was markedly reduced
      (IC50 25 microg/ml), while that of PCV remained relatively low (IC50 10
      microg/ml). Although FHV-1 is normally insensitive to ACV, it exhibited >1000
      fold increase in sensitivity when the thymidine kinase (TK) encoded by herpes
      simplex virus-1 (HSV-1) was supplied in trans. Furthermore, three PCV-resistant
      FHV-1 variants selected in vitro were shown to carry mutations in the TK gene.
      Taken together, these data provided direct evidence that PCV is a potent
      selective inhibitor of FHV-1 and that the virus-encoded TK is an important
      determinant of the virus susceptibility to nucleoside analogues.

PMID- 18325607
TI  - Expression of the human cytomegalovirus UL97 gene in a chimeric guinea pig
      cytomegalovirus (GPCMV) results in viable virus with increased susceptibility to
      ganciclovir and maribavir.
AB  - In lieu of a licensed vaccine, antivirals are being considered as an intervention
      to prevent congenital human cytomegalovirus (HCMV) infection. Ideally, antiviral
      therapies should undergo pre-clinical evaluation in an animal model prior to
      human use. Guinea pig cytomegalovirus (GPCMV) is the only small animal model for
      congenital CMV. However, GPCMV is not susceptible to the most commonly used HCMV
      antiviral, ganciclovir (GCV), rendering in vivo study of this agent problematic
      in the guinea pig model. Human cytomegalovirus (HCMV) susceptibility to GCV is
      linked to the UL97 gene. We hypothesized that GPCMV susceptibility to GCV could
      be improved by inserting the HCMV (Towne) UL97 gene into the GPCMV genome in
      place of the homolog, GP97. A chimeric GPCMV (GPCMV::UL97) expressed UL97
      protein, and replicated efficiently in cell culture, with kinetics similar to
      wild-type GPCMV. In contrast, deletion of GP97 resulted in a virus (GPCMVdGP97)
      that grew poorly in culture. GPCMV::UL97 had substantially improved
      susceptibility to the inhibitory effects of GCV in comparison to wild-type GPCMV.
      Additionally, GPCMV::UL97 exhibited improved susceptibility to another antiviral
      undergoing clinical trials, maribavir (MBV; benzimidazole riboside 1263W94),
      which also acts through UL97.

PMID- 18325608
TI  - Restraining tumor necrosis factor-alpha by thalidomide prevents the amyloid beta
      induced impairment of recognition memory in mice.
AB  - No effective remedy has currently been realized to prevent the cognitive
      impairments of Alzheimer's disease (AD). The interruption of the toxic pathways
      of amyloid beta peptide (Abeta) still remains promising for the treatment. The
      involvement of tumor necrosis factor-alpha (TNF-alpha) in the toxicity of Abeta(1
      40) in recent reports provide a fresh target for the interruption. In the current
      study, we evaluated the feasibility of a strategy that target TNF-alpha to
      prevent the impairment of memory induced by Abeta. The i.c.v-injection of
      Abeta(25-35) increased the hippocampal mRNA expression of both TNF-alpha and
      inducible nitric oxide synthase (iNOS), of which the former was stronger. The
      knock-out of TNF-alpha (TNF-alpha (-/-)) in mouse prevented the increase of iNOS
      mRNA induced by Abeta(25-35). Not only the inhibition of iNOS activity but also
      TNF-alpha (-/-) prevented the nitration of proteins in the hippocampus and the
      impairment of recognition memory in mice induced by Abeta(25-35). Daily treatment
      with thalidomide (20 mg/kg), a preferential degrader of TNF-alpha mRNA, or i.c.v.
      injection of an anti-TNF-alpha antibody (10 etag/mouse) prevented the nitration
      of proteins in the hippocampus and the impairment of recognition memory induced
      by Abeta(25-35) or Abeta(1-40) in mice. These results suggested the
      practicability of targeting TNF-alpha as a preventive strategy against Abeta
      mediated cognitive impairments.

PMID- 18325609
TI  - Motor coordination defects in mice deficient for the Sam68 RNA-binding protein.
AB  - The role of RNA-binding proteins in the central nervous system and more
      specifically their role in motor coordination and learning are poorly understood.
      We previously reported that ablation of RNA-binding protein Sam68 in mice results
      in male sterility and delayed mammary gland development and protection against
      osteoporosis in females. Sam68 however is highly expressed in most regions of the
      brain especially the cerebellum and thus we investigated the cerebellar-related
      manifestations in Sam68-null mice. We analyzed the mice for motor function,
      sensory function, and learning and memory abilities. Herein, we report that Sam68
      null mice have motor coordination defects as assessed by beam walking and rotorod
      performance. Forty-week-old Sam68-null mice (n=12) were compared to their wild
      type littermates (n=12). The Sam68-null mice exhibited more hindpaw faults in
      beam walking tests and fell from the rotating drum at lower speeds and
      prematurely compared to the wild-type controls. The Sam68-null mice were,
      however, normal for forelimb strength, tail-hang reflex, balance test, grid
      walking, the Morris water task, recognition memory, visual discrimination,
      auditory stimulation and conditional taste aversion. Our findings support a role
      for Sam68 in the central nervous system in the regulation of motor coordination.

PMID- 18325610
TI  - Increased effects of internal alpha irradiation in Daphnia magna after chronic
      exposure over three successive generations.
AB  - A 70-day experiment was performed with Daphnia magna exposed to waterborne Am-241
      on a range of concentrations (from 0.4 to 40 Bq ml(-1)) in order to test chronic
      effects of internal alpha irradiation on respiration, somatic growth and
      reproduction over three successive generations. Changes in Am-241 concentrations
      were followed in the water and in daphnid tissues, eggs and cuticles.
      Corresponding average dose rates of 0.3, 1.5 and 15 mGy h(-1) were estimated.
      This study confirmed that oxygen consumption increased significantly in the first
      generation (F0) after 6 days of exposure to a dose rate >or=1.5 mGy h(-1).
      Consequences were limited to a reduction in body length (5%) and dry mass of
      females (16%) and eggs (8%) after 23 days of exposure, while mortality and
      fecundity remained unaffected. New cohorts were started with neonates of broods 1
      and 5, to examine potential consequences of the reduced mass of offspring for
      subsequent exposed generations. Results strongly contrasted with those observed
      in F0. At the highest dose rate, an early mortality of 38-90% affected juveniles
      while survivors showed delayed reproduction and reduced fecundity in F1 and F2.
      At 0.3 and 1.5 mGy h(-1), mortality ranged from 31 to 38% of daphnids depending
      on dose rate, but was observed only in generation F1 started with neonates of the
      brood 1. Reproduction was affected through a reduction in the proportion of
      breeding females, occurring in the first offspring generation at 1.5 mGy h(-1)
      (to 62% of total daphnids) and in the second generation at 0.3 mGy h(-1) (to 69%
      of total daphnids). Oxygen consumption remained significantly higher at dose
      rates >or=0.3 mGy h(-1) than in the control in almost every generation. Body size
      and mass continued decreasing in relation to dose rate, with a significant
      reduction in mass ranging from 15% at 0.3 mGy h(-1) to 27% at 15 mGy h(-1) in the
      second offspring generation.

PMID- 18325612
TI  - The use of SSCP analysis in the assessment of phytoplasma gene variability.
AB  - Single-strand conformation polymorphism (SSCP) analysis is a broadly used
      technique for detecting mutations. The aim of this work was to assess the
      applicability of SSCP as a new tool for the detection of the molecular
      variability of uncultivable mollicutes - phytoplasmas. Three phytoplasma regions
      were investigated: 16S rDNA, tuf gene, and dnaB gene. Fragments amplified by PCR
      were subjected to SSCP under conditions optimized for each fragment length. In
      all of the analyzed regions, SSCP revealed the presence of polymorphism
      undetected by routine RFLP analyses. Reliability of the method was confirmed by
      the multiple alignments and phylogenetic analyses of representative sequences
      showing different SSCP profiles.

PMID- 18325611
TI  - Characterization of the mitochondrial inner membrane protein translocator Tim17
      from Trypanosoma brucei.
AB  - Mitochondrial protein translocation machinery in the kinetoplastid parasites,
      like Trypanosoma brucei, has been characterized poorly. In T. brucei genome
      database, one homolog for a protein translocator of mitochondrial inner membrane
      (Tim) has been found, which is closely related to Tim17 from other species. The
      T. brucei Tim17 (TbTim17) has a molecular mass 16.2kDa and it possesses four
      characteristic transmembrane domains. The protein is localized in the
      mitochondrial inner membrane. The level of TbTim17 protein is 6-7-fold higher in
      the procyclic form that has a fully active mitochondrion, than in the mammalian
      bloodstream form of T. brucei, where many of the mitochondrial activities are
      suppressed. Knockdown of TbTim17 expression by RNAi caused a cessation of cell
      growth in the procyclic form and reduced growth rate in the bloodstream form.
      Depletion of TbTim17 decreased mitochondrial membrane potential more in the
      procyclic than bloodstream form. However, TbTim17 knockdown reduced the
      expression level of several nuclear encoded mitochondrial proteins in both the
      forms. Furthermore, import of presequence containing nuclear encoded
      mitochondrial proteins was significantly reduced in TbTim17 depleted mitochondria
      of the procyclic as well as the bloodstream form, confirming that TbTim17 is
      critical for mitochondrial protein import in both developmental forms. Together,
      these show that TbTim17 is the translocator of nuclear encoded mitochondrial
      proteins and its expression is regulated according to mitochondrial activities in
      T. brucei.

PMID- 18325613
TI  - Functional columns in the primate prefrontal cortex revealed by optical imaging
      in vitro.
AB  - Although the functional column has been implicated in the dorsolateral prefrontal
      cortex (DLPFC) of primates, its dynamics and even existence are still uncertain.
      We performed optical recording with a voltage-sensitive dye (RH482) in brain
      slices obtained from the principal sulcal region (area 46) of macaque monkeys.
      Columnar activity was evoked by electrical stimulation of the middle layer (lower
      layer III or layer IV); this activity consisted of two components: probably
      action potentials and excitatory postsynaptic potentials. The width of the
      columnar activity was saturated when the current intensity of stimulation
      exceeded a certain level, that is, approximately 900 microm at the peak with this
      intensity. The stimulation of different sites within the same slice activated
      different columnar activities with only slight overlaps. Furthermore, similar
      columnar activity appeared when a different site within the area with columnar
      activity was stimulated. These findings suggest that the primate DLPFC consists
      of functional columns formed by excitatory synaptic connections.

PMID- 18325614
TI  - Differential cholinergic modulation of synaptic encoding and gain control
      mechanisms in rat hippocampus.
AB  - Recent studies have highlighted a variety of cognitive effects caused by
      cholinolytic drug injections into different cortical structures. These findings
      were largely interpreted as evidence for location-specific cholinergic modulation
      of synaptic encoding mechanisms. Here, using evoked field responses in
      anaesthetized rat dorsal hippocampus we show that in addition to reinforcement of
      synaptic connections (long-term potentiation, LTP), endogenous acetylcholine also
      regulates firing gain of CA1 pyramidal neurons (EPSP-spike potentiation). Gain
      augmentation upon increase in cholinergic drive involves evoked synchronous
      firing at both apical and basal afferent projections, unlike enhancement of
      activity-induced LTP constrained to the basal afferent system. These data
      indicate that acetylcholine can act as an effective input and gain controller in
      the hippocampus. Modulation of synaptic plasticity would determine the relative
      dominance of afferent inputs while the facilitation of synchronous firing is
      likely to promote a more generalized spread of excitation and long range
      communication within the limbic cortex.

PMID- 18325615
TI  - Epidemiological analysis of Salmonella enterica from beef sampled in the
      slaughterhouse and retailers in Dakar (Senegal) using pulsed-field gel
      electrophoresis and antibiotic susceptibility testing.
AB  - Seventy-eight isolates of Salmonella spp. isolated from beef sampled from the
      official city slaughterhouse and from retailers in Dakar, Senegal were analyzed
      using serotyping, antimicrobial testing and macrorestriction profiling by Pulsed
      Field Gel Electrophoresis (PFGE). These analyses were done to identify clonal
      relationships and potential transmission routes in beef channel. XbaI
      macrorestriction allowed defining 17 genotypes among the six main analyzed
      serotypes: Salmonella bredeney (3 genotypes), S. muenster (6), S. waycross (1),
      S. corvallis (3), S. kentucky (1) and S. brandenburg (3). The cross analysis of
      PFGE profiles and origin of the beef samples reveals a wide range of
      contamination sources in the beef channel in Dakar. Comparison of PFGE and
      antimicrobial resistance types shows that the Salmonella contamination sources
      are equally shared by the slaughterhouse (56% of the isolates) and by the
      distribution channel (44% of the isolates) by handlings and houseflies.

PMID- 18325616
TI  - HCV core protein interacts with Dicer to antagonize RNA silencing.
AB  - RNA silencing is a form of nucleic acid-based immunity against viruses in plants
      and invertebrate animals. Successful viral infection requires evasion or
      suppression of gene silencing. Here, we report that the core protein of Hepatitis
      C virus (HCV) acts as a potent suppressor of RNA silencing (SRS). We have found
      that the HCV core protein inhibits RNA silencing induced by short hairpin RNAs
      (shRNAs) but not by synthetic small interfering RNAs (siRNAs) in various
      mammalian cells. We have further demonstrated that HCV core protein directly
      interacts with Dicer, an RNase enzyme that generates siRNA in host cells. The HCV
      core protein has been shown to inhibit the function of Dicer to process double
      stranded RNAs (dsRNAs) into siRNAs. Through deletion analysis, we have found that
      the N-terminal domain is required for core protein to antagonize RNA silencing
      activity of Dicer enzyme. Thus, our results suggest that HCV core protein may
      abrogate host cell RNA silencing defense by suppressing the ability of Dicer to
      process precursor dsRNAs into siRNAs. This anti-Dicer ability of core protein may
      contribute to the persistent viral infection and pathogenesis of HCV.

PMID- 18325617
TI  - Controlled release of amoxicillin from hydroxyapatite-coated poly(lactic-co
      glycolic acid) microspheres.
AB  - Negatively charged poly(lactic-co-glycolic acid) (PLGA) microspheres with an
      encapsulated hydrophilic antibiotic (amoxicillin) have been prepared by the solid
      in-oil-in-water (s/o/w) method using the anionic surfactant, sodium dodecyl
      sulfate (SDS). Drug encapsulation efficiency is over 40%. Successful coating of
      hydroxyapatite (HA) on these negatively charged PLGA microspheres has been
      achieved by a dual constant composition method in 3-6 h. The HA-coated PLGA
      microspheres (HPLG) have been characterised by zeta-potential and particle size
      measurements and the coating has been confirmed to be calcium deficient HA by
      analysis of X-ray diffraction, Fourier transform infrared spectroscopy and
      wavelength dispersive spectroscopy. The morphology of HPLG was studied by
      scanning electron microscopy, and cross sections of HPLG microspheres were
      prepared and imaged using focused ion beam microscopy. In-vitro drug release
      experiments in PBS (pH7.4) showed a sustained release profile for at least 31
      days with little initial burst release. It shows a triphasic drug release profile
      commonly observed for biodegradable polymers.

PMID- 18325618
TI  - Doxorubicin release is not a prerequisite for the in vitro cytotoxicity of HPMA
      based pharmaceuticals: in vitro effect of extra drug-free GlyPheLeuGly sequences.
AB  - A systematic study was designed to elucidate differences in cytostatic activity
      in vitro between HPMA-based doxorubicin conjugates synthesized using different
      polymerization techniques and differing in peptidyl side chain. A polymer-drug
      conjugate containing doxorubicin (DOX) bound to HPMA copolymer backbone through
      the enzymaticaly non-cleavable sequence GlyGly shows low but significant
      cytotoxicity in vitro in seven cancer cell lines of mouse (EL4, 38C13, 3T3, BCL1)
      and human (SW620, Raji, Jurkat) origin. The low cytotoxicity can be considerably
      increased by the presence of additional drug-free GlyPheLeuGly side chains. P1
      conjugate, i.e. non-targeted HPMA copolymer bearing doxorubicin bound via a
      biodegradable GlyPheLeuGly sequence, synthesized by direct copolymerization of
      HPMA with monomeric doxorubicin and thus without additional drug-free
      GlyPheLeuGly sequences is less effective compared to PK1 synthesized by polymer
      analogous reaction and thus containing extra drug-free GlyPheLeuGly sequences.
      Significant activity-enhancing effect was not seen with other amino
      acid/oligopeptide sequences (e.g., Gly or GlyGly). The activity-enhancing effect
      of GlyPheLeuGly sequences is more obvious in the conjugate containing doxorubicin
      bound to HPMA through GlyGly sequence. Derivatization of the terminal carboxyl
      group of the extra GlyPheLeuGly side chains (amide, N-substituted amide, free
      carboxyl) does not significantly influence the cytotoxicity of the conjugates.
      The presence of the GlyPheLeuGly sequence in the conjugate structure increases
      its rate of intracellular accumulation. Normal cells (Balb/c splenocytes)
      accumulate less polymer-doxorubicin conjugate compared to cancer cells (T cell
      lymphoma EL4, B cell lymphoma Raji and T cell leukemia JURKAT).

PMID- 18325619
TI  - Polymeric micelles in oral chemotherapy.
AB  - Oral administration of anticancer agents is preferred by patients for its
      convenience and potential for use in outpatient and palliative setting. In
      addition, oral administration facilitates a prolonged exposure to the cytotoxic
      agents. Enhancement of bioavailability of emerging cytotoxic agents is a pre
      requisite for successful development of oral modes of cancer treatment. Over the
      last decade, our studies have focused specifically on the utilization of large
      (MW>10(5)) and non-degradable polymers in oral chemotherapy. A family of block
      graft copolymers of the poly(ethylene oxide) (PEO) and poly(propylene oxide)
      (PPO) Pluronic(R) polyethers and poly(acrylic acid) (PAA) bound by carbon-carbon
      bonds emerged, wherein both polymeric components are generally recognized as
      safe. Animal studies with Pluronic-PAA copolymers demonstrated that these
      molecules are excreted when administered orally and do not absorb into the
      systemic circulation. The Pluronic-PAA copolymers are surface-active and self
      assemble, at physiological pH, into intra- and intermolecular micelles with
      hydrophobic cores of dehydrated PPO and multilayered coronas of hydrophilic PEO
      and partially ionized PAA segments. These micelles efficiently solubilize
      hydrophobic drugs such as paclitaxel and steroids and protect molecules such as
      camptothecins from the hydrolytic reactions. High surface activity of the
      Pluronic-PAA copolymers in water results in interactions with cell membranes and
      suppression of the membrane pumps such as P-glycoprotein. The ionizable carboxyls
      in the micellar corona facilitate mucoadhesion that enhances the residence time
      of the micelles and solubilized drugs in the gastrointestinal tract. Large
      payloads of the Pluronic-PAA micelles with weakly basic and water-soluble drugs
      such as doxorubicin and its analogs, mitomycin C, mitoxantrone, fluorouracil, and
      cyclophosphamide are achieved through electrostatic interactions with the
      micellar corona. Mechanical and physical properties of the Pluronic-PAA powders,
      blends, and micelles allow for formulation procedures where an active is simply
      dispersed into an aqueous Pluronic-PAA micellar formulation followed by optional
      lyophilization and processing into a ready dosage form. We review a number of in
      vivo and in vitro experiments demonstrating that that the oral administration of
      the cytotoxics formulated with the Pluronic-PAA copolymer micelles results in
      enhanced drug bioavailability.

PMID- 18325620
TI  - Glucose variability, blood pressure and arterial stiffness in type 1 diabetes.
AB  - AIMS: Evidence suggests that chronic hyperglycaemia predicts not only
      microvascular disease but also macrovascular disease, however it is not known
      whether it is the glucose variability per se or the total glucose exposure that
      confers risk. The objective of this study was to investigate whether daily
      glucose variability influence blood pressure and arterial stiffness, an early
      sign of macrovascular disease, at baseline and during a hyperglycaemic clamp in
      patients with type 1 diabetes. METHODS: Twenty-two non-smoking male patients with
      type 1 diabetes without any diabetic complications, participated in the study.
      The patients were monitored for 72-h using a continuous glucose monitoring
      system. Before and during a 2-h hyperglycaemic clamp, blood pressure as well as
      pulse wave analysis and pulse wave velocity (PWV) were performed to assess
      arterial stiffness. RESULTS: No correlation was observed between mean amplitude
      of glycaemic excursions (MAGE) and arterial stiffness at baseline. There was a
      correlation between mean daily glucose and aortic PWV even after adjusting for
      BMI, HbA(1c), and duration of diabetes in a multiple regression analysis (r=0.48;
      P<0.01). MAGE (r=0.52; P<0.01) correlated independently with the change in aortic
      DBP during the clamp. CONCLUSIONS: This study suggests that high mean daily blood
      glucose but not glucose variability per se is associated with arterial stiffness
      in patients with T1D. Daily glucose variability is positively associated with the
      change in central blood pressure during a hyperglycaemic clamp.

PMID- 18325621
TI  - Improving public addiction treatment through performance contracting: the
      Delaware experiment.
AB  - In fiscal 2002, Delaware replaced traditional cost-reimbursement contracts with
      performance-based contracts for all outpatient addiction treatment programs.
      Incentives included 90% capacity utilization and active patient participation in
      treatment. One of the programs failed to meet requirements. Strategies adopted by
      successful programs included extended hours of operation, facility enhancements,
      salary incentives for counselors, and two evidence-based therapies (MI and CBT).
      Average capacity utilization from 2001 to 2006 went from 54% to 95%; and the
      average proportion of patients' meeting participation requirements went from 53%
      to 70%--with no notable changes in the patient population. We conclude that
      properly designed, program-based contract incentives are feasible to apply,
      welcomed by programs and may help set the financial conditions necessary to
      implement other evidence-based clinical efforts; toward the overall goal of
      improving addiction treatment.

PMID- 18325622
TI  - Impact of the reduction of the prescription charge in Wales on the prescribing of
      non-sedating antihistamines in primary care.
AB  - OBJECTIVE: Determine the impact of the phased reduction of the prescription
      charge in Wales on prescriptions for non-sedating antihistamines. METHOD:
      Prescription items for non-sedating antihistamines dispensed in 22 Local Health
      Boards (LHBs) in Wales and 15 Primary Care Trusts in the South East of England
      were analysed between October 2001 and September 2006. RESULTS: There was an
      increase in percent change (median (interquartile range [IQR])) in prescription
      items for non-sedating antihistamines dispensed in Wales in the 24 months after
      the first reduction of the prescription charge in October 2004 compared to the 24
      months prior to this (13.7 [10.9-17.1] vs. 7.3 [5.0-10.7], p<0.001). In the South
      East of England there was no change over the same periods (4.4 [3.4-7.5] vs. 4.5
      [0.8-7.9], p=0.73). In the five least deprived LHBs the percent change in
      prescriptions for non-sedating antihistamines increased in the 24 months after
      the reduction of the prescription charge compared to the previous 24 months (14.3
      [11.5-19.4] vs. 9.0 [9.1-13.5], p=0.04). In contrast there was no change over the
      two periods in the five most deprived LHBs (13.1 [10.9-17.5] vs. 9.5 [2.9-10.4],
      p=0.08]. CONCLUSIONS: The phased reduction of the prescription charge in Wales
      coincided with an increase in the number of non-sedating antihistamines dispensed
      in Wales. This was only evident in the least deprived LHBs.

PMID- 18325623
TI  - Mixing and matching: the essence of plant systemic silencing?
AB  - In plants and some animals, posttranscriptional RNA silencing can be manifested
      beyond its sites of initiation, because of the movement of signaling molecules
      that must have RNA components to account for the nucleotide sequence specificity
      of their effects. In a recent study carried out in Arabidopsis thaliana,
      interesting clues were provided that suggest mechanisms by which systemic RNA
      silencing signals might be produced and perceived between distant plant organs.

PMID- 18325624
TI  - The methylome: approaches for global DNA methylation profiling.
AB  - DNA methylation plays a critical role in genome function both in health and
      disease. Almost 60 years after the discovery of 5-methyl cytosine and
      approximately 25 years since the discovery that altered DNA methylation plays a
      role in disease, the first high-resolution DNA methylation profile (or methylome)
      of any genome--Arabidopsis thaliana--was determined. Although only approximately
      20% of the typical size of mammalian genomes, this milestone demonstrated that
      the methylomes of the human and similarly large genomes are now within reach.
      Here, we review current and emerging technologies that hold promise to deliver
      the first mammalian methylome and to facilitate comprehensive profiling of
      essentially any cell type in the context of development, disease and the
      environment.

PMID- 18325625
TI  - Adapting to environmental changes using specialized paralogs.
AB  - When a bacterial species survives under changing environmental circumstances
      (e.g. salinity or temperature), its proteins might not function in all
      physicochemical conditions. We propose that prokaryotes cope with this problem by
      having two or more copies of the genes affected by environmental fluctuations,
      each one performing the same function under different conditions (i.e.
      ecoparalog). We identify potential examples in the bacterium Salinibacter ruber
      and in other species that experience wide environmental variations.

PMID- 18325626
TI  - Beyond induced mutants: using worms to study natural variation in genetic
      pathways.
AB  - Induced mutants in the nematode Caenorhabditis elegans are used to study genetic
      pathways of processes ranging from aging to behavior. The effects of such
      mutations are usually analyzed in a single wildtype background: N2. However,
      studies in other species demonstrate that the phenotype(s) of induced mutations
      can vary widely depending on the genetic background. Moreover, induced mutations
      in one genetic background do not reveal the allelic effects that segregate in
      natural populations and contribute to phenotypic variation. Because other
      wildtype Caenorhabditis spp., including C. elegans, are now available, we review
      how current mapping resources and methodologies within and between species
      support the use of Caenorhabditis spp. for studying genetic variation, with a
      focus on pathways associated with human disease.

PMID- 18325627
TI  - MicroRNAs flex their muscles.
AB  - MicroRNAs negatively regulate gene expression by promoting mRNA degradation and
      inhibiting mRNA translation. Recent studies have uncovered a cadre of muscle
      specific microRNAs that regulate diverse aspects of muscle function, including
      myoblast proliferation, differentiation, contractility and stress responsiveness.
      These myogenic microRNAs, which are encoded by bicistronic transcripts or are
      nestled within introns of myosin genes, modulate muscle functions by fine-tuning
      gene expression patterns or acting as 'on-off' switches. Muscle-specific
      microRNAs also participate in numerous diseases, including cardiac hypertrophy,
      heart failure, cardiac arrhythmias, congenital heart disease and muscular
      dystrophy. The myriad roles of microRNAs in muscle biology pose interesting
      prospects for their therapeutic manipulation in muscle disease.

PMID- 18325628
TI  - Nanotechnology in vaccine delivery.
AB  - With very few adjuvants currently being used in marketed human vaccines, a
      critical need exists for novel immunopotentiators and delivery vehicles capable
      of eliciting humoral, cellular and mucosal immunity. Such crucial vaccine
      components could facilitate the development of novel vaccines for viral and
      parasitic infections, such as hepatitis, HIV, malaria, cancer, etc. In this
      review, we discuss clinical trial results for various vaccine adjuvants and
      delivery vehicles being developed that are approximately nanoscale (<1000 nm) in
      size. Humoral immune responses have been observed for most adjuvants and delivery
      platforms while only viral vectors, ISCOMs and Montanide ISA 51 and 720 have
      shown cytotoxic T cell responses in the clinic. MF59 and MPL have elicited Th1
      responses, and virus-like particles, non-degradable nanoparticles and liposomes
      have also generated cellular immunity. Such vaccine components have also been
      evaluated for alternative routes of administration with clinical successes
      reported for intranasal delivery of viral vectors and proteosomes and oral
      delivery of a VLP vaccine.

PMID- 18325629
TI  - Radial artery pseudoaneurysm formation after cat bite to the wrist.
AB  - Pseudoaneurysms may occur in the groin after catheterization of the femoral
      artery but may also occur in arteriovenous shunting for dialysis after placement
      of indwelling catheters or after direct trauma to an artery. We report a unique
      cause of radial artery pseudoaneurysm at the wrist related to a cat bite
      sustained by an elderly woman. The patient underwent successful operative repair
      of the aneurysm, with ligation of the radial artery.

PMID- 18325630
TI  - The effect of pea albumin 1F on glucose metabolism in mice.
AB  - Pea albumin 1F (PA1F), a plant peptide isolated from pea seeds, can dramatically
      increase blood glucose concentration by subcutaneous injection with a dosage of 5
      or 10 microg/g (body weight) in normal and type II diabetic mice (KK/upj-Ay). The
      voltage-dependent anion channel 1 (VDAC-1) has been identified as the PA1F
      binding protein from mice pancreatic cell membrane, which may be involved in the
      regulation of enhancing blood glucose in response to PA1F binding. The results
      clearly show that peptide-signaling molecules from plants can affect mammalian
      physiological functions, especially, in association with glucose metabolism.

PMID- 18325631
TI  - Characterization and functional recovery of a novel antimicrobial peptide (CECdir
      CECret) from inclusion bodies after expression in Escherichia coli.
AB  - CECdir-CECret is a novel non-toxic doublet 8.5 kDa peptide representing the
      natural coding sequence of the antimicrobial peptide Cecropin A from Drosophila
      melanogaster fused in-frame to its own inverted version. Expression of this
      cloned doublet peptide in Escherichia coli, yielded peptides that were mostly
      packaged into inclusion bodies. The new molecule was purified, solubilized and
      refolded, through a standard guanidine-based procedure. The recovered refolded
      peptides were then characterized by HPLC chromatography, MALDI-TOF-mass
      spectrometry and peptide sequencing, and finally evaluated for their
      antimicrobial potential. The novel doublet peptide CECdir-CECret, displays an
      enhanced in vitro antimicrobial activity and action spectrum in comparison to the
      monomer Cecropin A.

PMID- 18325632
TI  - Increased leptin expression selectively in the hypothalamus suppresses
      inflammatory markers CRP and IL-6 in leptin-deficient diabetic obese mice.
AB  - Low-grade systemic inflammation, as indicated by increased circulating levels of
      inflammatory markers CRP and IL-6, is linked to increased risks for
      cardiovascular diseases (CVD) and diabetes mellitus in obese subjects. Whereas
      hyperleptinemia in obesity are associated with increased CRP and IL-6 release,
      the hypothalamic versus peripheral site of leptin action has not been
      ascertained. The effects of increased leptin supply selectively in the
      hypothalamus by gene therapy on pro-inflammatory CRP and IL-6 levels and on
      markers of diabetes in the circulation of ob/ob mice displaying either age
      related or dietary obesity were assessed. A recombinant adeno-associated viral
      vector encoding either green-fluorescent protein (control) or leptin gene was
      injected intracerebroventricularly. Five weeks later, one-half of each of the
      vector groups was switched to high-fat diet consumption and the other half
      continued to consume regular low-fat chow diet. Body weight and visceral white
      adipose tissue were drastically reduced and hyperinsulinemia and hyperglycemia
      were abrogated by leptin gene therapy, independent of the dietary fat content.
      The elevated plasma CRP and IL-6 levels seen in obese ob/ob mice receiving the
      control vector, regardless of the fat content of the diet, were markedly
      suppressed by increased hypothalamic leptin in both groups. The results show for
      the first time that leptin deficiency elevates and reinstatement of leptin
      selectively in the hypothalamus suppresses the release of pro-inflammatory
      biomarkers, a response likely to alleviate CVD associated with obesity.

PMID- 18325633
TI  - Obestatin: its physicochemical characteristics and physiological functions.
AB  - Obestatin, a novel 23 amino acid amidated peptide encoded by the same gene with
      ghrelin, was initially reported to reduce food intake, body weight gain, gastric
      emptying and suppress intestinal motility through an interaction with the orphan
      receptor GPR39. However, recently reports have shown that above findings had been
      questioned by several groups. Further studies explained that obestatin was
      involved in inhibiting thirst and anxiety, improving memory, regulating sleep,
      affecting cell proliferation, and increasing the secretion of pancreatic juice
      enzymes. We also identified that obestatin could stimulate piglet liver and
      adipose cell proliferation, and inhibit the secretion of IGF-I. According to the
      controversy over the effects and the cognate ligand of obestatin, here we provide
      the latest review on the structure, distribution and physiological functions of
      obestatin.

PMID- 18325634
TI  - Tumor necrosis factor receptor-associated death domain mediated neuronal death
      contributes to the glial activation and subsequent neuroinflammation in Japanese
      encephalitis.
AB  - While a number of studies have documented the importance of microglia in central
      nervous system (CNS) response to injury, infection and in disease state, little
      is known regarding how the neuronal death initiates the cascades of secondary
      neuroinflammation. We have exploited an experimental model of Japanese
      encephalitis to better understand how neuronal death following viral infection
      initiates microglial activation following Japanese encephalitis virus infection.
      We have earlier shown that the altered expression of tumor necrosis factor
      receptor-1 (TNFR-1) and TNFR associated death domain (TRADD) following Japanese
      encephalitis virus infection regulates the downstream apoptotic cascades. Here we
      have reported that silencing TRADD expression with small-interfering RNA reduced
      neuronal apoptosis and subsequent microglial and astroglial activation and
      release of various pro-inflammatory mediators. Our findings suggest that the
      engagement of TNFR-1 and TRADD following Japanese encephalitis virus infection
      plays a crucial role in glial activation also and influences the outcome of viral
      pathogenesis.

PMID- 18325635
TI  - Microglial responses to dopamine in a cell culture model of Parkinson's disease.
AB  - Activated microglia appear to selectively attack dopamine (DA) neurons in the
      Parkinson's disease (PD) substantia nigra. We investigated potential mechanisms
      using culture models. As targets, human SH-SY5Y cells were left undifferentiated
      (UNDIFF) or were differentiated with retinoic acid (RA) or RA plus brain-derived
      neurotrophic factor (RA/BDNF). RA/BDNF-treated cells were immunoreactive for
      tyrosine hydroxylase and the DA transporter, took up exogenous DA, and released
      DA after K(+) stimulation. Undifferentiated and RA-treated cells lacked these
      characteristics of a DA phenotype. Co-culture of target cells with human elderly
      microglia resulted in elevated toxicity in DA phenotype (RA/BDNF) cells.
      Lipopolysaccharide (LPS) plus K(+)-stimulated DA release enhanced toxicity by 500
      fold. DA induced microglial chemotaxis in Boyden chambers. Spiperone inhibited
      this effect. Cultured human elderly microglia expressed mRNAs for D1-D4 but not
      D5 DA receptors. The microglia, as well as PD microglia in situ, were also
      immunoreactive for D1-D4 but not D5 DA receptors. These findings demonstrate that
      activated microglia express DA receptors, and suggest that this mechanism may
      play a role in the selective vulnerability of DA neurons in PD.

PMID- 18325636
TI  - Cerebral perfusion and oxygenation differences in Alzheimer's disease risk.
AB  - Functional MRI has demonstrated differences in response to memory performance
      based on risk for Alzheimer's disease (AD). The current study compared blood
      oxygen level dependent (BOLD) functional MRI response with arterial spin labeling
      (ASL) perfusion response during an associative encoding task and resting
      perfusion signal in different risk groups for AD. Thirteen individuals with a
      positive family history of AD and at least one copy of the apolipoprotien E
      epsilon4 (APOE4) gene (high risk) were compared to ten individuals without these
      risk factors (low risk). In the medial temporal lobes (MTLs) the high risk group
      had an elevated level of resting perfusion, and demonstrated decreased fractional
      BOLD and perfusion responses to the encoding task. However, there was no
      difference in the absolute cerebral blood flow during the task. These data
      demonstrate that individuals with increased risk for Alzheimer's disease have
      elevated MTL resting cerebral blood flow, which significantly influences apparent
      differences in BOLD activations. BOLD activations should be interpreted with
      caution, and do not necessarily reflect differences in neuronal activation.

PMID- 18325637
TI  - Pyrazoles and pyrazolines as neural and inducible nitric oxide synthase (nNOS and
      iNOS) potential inhibitors (III).
AB  - We have previously described a series of 4,5-dihydro-1H-pyrazole as moderately
      potent nNOS inhibitors. As a follow up of these studies, we report here the
      preparation and the preliminary evaluation of a series of 1-alkyl-3-benzoyl-4,5
      dihydro-1H-pyrazole and 1-alkyl-3-benzoyl-1H-pyrazole as potential inhibitors of
      both neuronal and inducible nitric oxide synthases (nNOS and iNOS). None of the
      reported compounds exhibited significant iNOS or nNOS inhibition, although the 1
      benzyl-3-(2-amino-5-chlorobenzoyl)-1H-pyrazole-5-carboxylic acid ethyl ester
      derivative (10l), which shows an inhibition of 50% versus iNOS at a 1mM final
      concentration and no activity against nNOS, is potentially amenable of further
      optimization. The reasons for the inactivity of the reported series are discussed
      on the basis of docking studies.

PMID- 18325638
TI  - [Chronic sciatic pain caused by sciatic nerve schwannoma].
AB  - Schwannomas are tumors with slowly progressive symptoms, more often painful than
      associated with neurologic deficits. Involvement of the sciatic nerve mimics
      chronic sciatic pain due to a herniated disk. If there is no lumbar pain and
      lumbar MRI is normal, the sciatic nerve must be clinically and radiologically
      examined all along its course. We report a patient with chronic sciatica in whom
      physical examination revealed a painful mass with a Tinel sign in her back thigh.
      MRI showed a multilobular mass along the sciatic nerve. Surgery of this plexiform
      schwannoma allowed a complete relief from pain.

PMID- 18325639
TI  - Influenza-related hospitalisation and death in Australians aged 50 years and
      older.
AB  - Estimating the true burden of influenza is problematic because relatively few
      hospitalisations or deaths are specifically coded as influenza related.
      Statistical regression techniques using influenza and respiratory syncytial virus
      surveillance data were used to estimate the number of excess hospitalisations and
      deaths attributable to influenza. Several International Classification of
      Diseases 10th Revision (ICD-10) groupings were used for both hospitalisation and
      mortality estimates, including influenza and pneumonia, other respiratory
      disorders, and circulatory disorders. For Australians aged 50-64 years, the
      annual excess hospitalisations attributable to influenza were 33.3 (95%CI: 23.2
      43.4) per 100,000 for influenza and pneumonia and 57.6 (95%CI: 32.5-82.8) per
      100,000 for other respiratory disorders. For Australians aged > or =65 years, the
      annual excess hospitalisations attributable to influenza were 157.4 (95%CI: 108.4
      206.5) per 100,000 for influenza and pneumonia and 282.0 (95%CI: 183.7-380.3) per
      100,000 for other respiratory disorders. The annual excess all-cause mortality
      attributable to influenza was 6.4 (95%CI: 2.6-10.2) per 100,000 and 116.4 (95%CI:
      71.3-161.5) per 100,000, for Australians aged 50-64 years and those aged > or =65
      years, respectively. In the age-group > or =65 years, a significant association
      was found between influenza activity and circulatory mortality. We conclude that
      influenza is responsible for a substantial amount of mortality and morbidity,
      over and above that which is directly diagnosed as influenza in Australians aged
      > or =50 years.

PMID- 18325640
TI  - Detecting AIDS restriction genes: from candidate genes to genome-wide association
      discovery.
AB  - The screening of common genetic polymorphisms among candidate genes for AIDS
      pathology in HIV exposed cohort populations has led to the description of 20 AIDS
      restriction genes (ARGs), variants that affect susceptibility to HIV infection or
      to AIDS progression. The combination of high-throughput genotyping platforms and
      the recent HapMap annotation of some 3 million human SNP variants has been
      developed for and applied to gene discovery in complex and multi-factorial
      diseases. Here, we explore novel computational approaches to ARG discovery which
      consider interacting analytical models, various genetic influences, and SNP
      haplotype/LD structure in AIDS cohort populations to determine if these ARGs
      could have been discovered using an unbiased genome-wide association approach.
      The procedures were evaluated by tracking the performance of haplotypes and SNPs
      within ARG regions to detect genetic association in the same AIDS cohort
      populations in which the ARGs were originally discovered. The methodology
      captures the signals of multiple non-independent AIDS-genetic association tests
      of different disease stages and uses association signal strength (odds ratio or
      relative hazard), statistical significance (p-values), gene influence, internal
      replication, and haplotype structure together as a multi-facetted approach to
      identifying important genetic associations within a deluge of genotyping/test
      data. The complementary approaches perform rather well and predict the detection
      of a variety of undiscovered ARGs that affect different stages of HIV/AIDS
      pathogenesis using genome-wide association analyses.

PMID- 18325641
TI  - An efficient plant viral expression system generating orally immunogenic Norwalk
      virus-like particles.
AB  - Virus-like particles (VLPs) derived from enteric pathogens like Norwalk virus
      (NV) are well suited to study oral immunization. We previously described stable
      transgenic plants that accumulate recombinant NV-like particles (rNVs) that were
      orally immunogenic in mice and humans. The transgenic approach suffers from long
      generation time and modest level of antigen accumulation. We now overcome these
      constraints with an efficient tobacco mosaic virus (TMV)-derived transient
      expression system using leaves of Nicotiana benthamiana. We produced properly
      assembled rNV at 0.8 mg/g leaf 12 days post-infection (dpi). Oral immunization of
      CD1 mice with 100 or 250 microg/dose of partially purified rNV elicited systemic
      and mucosal immune responses. We conclude that the plant viral transient
      expression system provides a robust research tool to generate abundant quantities
      of rNV as enriched, concentrated VLP preparations that are orally immunogenic.

PMID- 18325642
TI  - Impact and effectiveness of a mass hepatitis A vaccination programme of
      preadolescents seven years after introduction.
AB  - AIM: To investigate the impact of a mass hepatitis A vaccination programme in
      preadolescents seven years after introduction in terms of its effectiveness and
      the prevented fraction. SETTING: The age distribution of notified cases and
      incidence rates in Catalonia (Spain) in the periods before (1992-1998) and after
      (1999-2005) introduction of the vaccination programme were compared. MAIN
      RESULTS: The incidence rates in the whole population were 5.51 per 100,000 person
      years in the 1992-1998 period and 2.98 in the 1999-2005 period. The rate
      reduction in the 10-19 years age group was 72.43% and was more than 45% in the 5
      9 years and 20-29 years age groups. The effectiveness of the vaccination
      programme was 99.04 (95% CI: 93.11-99.88) and the prevented fraction in the 12-19
      years age group was 90.13% (95% CI: 84.47-90.89). CONCLUSIONS: The universal
      vaccination programme of preadolescents has had an important impact on hepatitis
      A in Catalonia, not only in vaccinated cohorts but also in non-vaccinated age
      groups due to a herd immunity effect.

PMID- 18325643
TI  - Associations between SNPs in toll-like receptors and related intracellular
      signaling molecules and immune responses to measles vaccine: preliminary results.
AB  - Toll-like receptors (TLRs) represent the critical "bridge" between innate and
      adaptive immunity to viral pathogens. We hypothesized that single nucleotide
      polymorphisms (SNPs) that potentially influence the expression/function of TLRs
      and their associated intracellular signaling molecules contribute to variations
      in humoral and cellular immunity to measles vaccine. We genotyped 190 randomly
      selected subjects (12-18 years old), previously vaccinated with two doses of
      measles, for known SNPs in TLR 2, 3, 4, 5, 6, 7, 8 and 9, and their associated
      intracellular signaling genes. Specific SNPs in the TLR 2, 3, 4, 5, 6, MyD88 and
      MD2 genes were associated with measles-specific humoral and cellular immunity.
      Heterozygous variants for rs3775291 (Phe412Leu) and rs5743305 (-926 bp in
      promoter region) of the TLR3 gene were associated with low antibody and
      lymphoproliferative responses (p <or= 0.02) to measles vaccination. Heterozygous
      variants for rs4986790 (Gly299Asp) and rs4986791 (Ile399Thr) in the TLR4 gene
      demonstrated higher levels of (p <or= 0.02) IL-4 secretion. Heterozygous variants
      for SNPs in TLR5 (rs5744174) and TLR6 (rs5743818) were associated with higher
      levels of (p <or= 0.02) IFN-gamma secretion. In addition, SNPs in MyD88 and MD2,
      intracellular molecules that associate with TLRs, also demonstrated associations
      with variations in antibody and IL-10 production (p <or= 0.03). Thus, we
      identified specific SNP associations between TLRs and their associated signaling
      molecules that have a known role in viral immunity and variations in both humoral
      and cellular immunity following measles vaccination. These data contribute to
      understanding the immunogenetic mechanisms underlying variations in the immune
      response to measles vaccine.

PMID- 18325644
TI  - Three-dimensional evaluation of secondary alveolar bone grafting using a 3D-
      navigation system based on computed tomography: a two-year follow-up.
AB  - Secondary bone grafting is widely used in the closure of oronasal fistulas and
      reconstruction of maxillary defects. It often fails from lack of physiological
      stress or inadequate covering of the transplanted bone with surrounding tissue.
      The aim of this study was to assess the exact bone volume after secondary
      alveolar bone grafting over a period of two years using a navigation system based
      on computed tomography (CT). We examined 20 patients with complete unilateral
      cleft lip and palate (UCLP) who had been treated by secondary bone grafting
      during late mixed dentition. CT scans of the upper jaw were taken immediately
      preoperatively, and 1 and 2 years postoperatively. The cleft defects and the bony
      bridges were marked on the monitor. The software of the navigation system created
      three-dimensional models showing the amount and site of bone resorption. The mean
      bone loss after one and two years was 51% and 52%, respectively. There was a
      significant correlation between the size of the cleft and the success of the
      alveolar bone grafting (p=0.01). When the teeth adjacent to the cleft were
      missing the amount of bone lost was 95% after the first year. There was also
      significant bone loss in the buccopalatine direction. Three-dimensional
      reconstruction of the bony bridges with a navigation system accurately shows the
      amount of bone within the cleft site. This method is definitely superior to
      conventional two-dimensional orthopantomography.

PMID- 18325645
TI  - Barriers to high-quality primary reproductive health services in an urban area of
      Iran: views of public health providers.
AB  - OBJECTIVE: to explore public primary reproductive health providers' views on
      their own roles and tasks in their present organisation, and the perceived
      barriers to providing high-quality services. DESIGN: a qualitative approach using
      semi-structured, audio-taped focus group discussions (FGDs). The discussions were
      held in Farsi or Turkish, transcribed verbatim, translated into English and
      analysed using content analysis. SETTING: family health units of public health
      facilities, Tabriz, Iran. PARTICIPANTS: two FGDs with 12 midwives and two FGDs
      with eight other family health providers working at the facilities. FINDINGS: the
      providers identified the most satisfying part of their duties as working with
      clients. A dominant theme in all FGDs was the providers' frustration about a
      number of factors, most of which were beyond their control. The identified system
      and organisational barriers were grouped into five categories: multiplicity of
      tasks and incompatibility with the providers' own basic training; suboptimal
      supervision and management; too little time for clients; lack of privacy and
      appropriate materials for education and counselling; and inadequate opportunities
      for continuing education. KEY CONCLUSIONS: this study highlighted the providers'
      satisfaction in working with clients, and their dissatisfaction with not being
      used to the best of their capabilities due to a number of systemic and
      organisational barriers. IMPLICATIONS FOR PRACTICE: based on these findings,
      multifaceted interventions seem to be necessary to improve staff productivity and
      service quality. The interventions should include needs-based pre-service
      education, supportive supervision and management, provision of educational
      materials, simplifying record management, and appointing more staff in socio
      economically deprived areas. Research is needed to identify the best way to
      integrate the services, as well as basic and continuing educational needs of
      staff.

PMID- 18325646
TI  - Effects of loading the unaffected limb for one session of locomotor training on
      laboratory measures of gait in stroke.
AB  - BACKGROUND: Walking following stroke involves compensatory strategies by the
      unaffected leg to cope with the deficits in the hemiparetic leg. Recently,
      training paradigms based on the principles of task-oriented repetitive exercise
      have provided a valuable insight regarding the influence of restraining
      compensatory movements to improve motor performances. We investigated changes in
      the walking movements of each lower extremity after weighting the unaffected leg.
      METHODS: Ten individuals early after a stroke (range: 3-7 months) who were able
      to walk 10 m with no aids, participated to this study. Subjects were instructed
      to walk on a treadmill with an external mass attached around the non affected
      ankle during a single session. The short-term effects on gait performance were
      quantified by a 3D-gait analysis system before, immediately after and 20 min
      after the walking technique. FINDINGS: A one factor repeated measures model
      revealed that stroke participants significantly improved in walking speed
      (P<0.001), step length (P<0.01) and cadence (P<0.01). Weight-bearing on the
      paretic leg increased (P<0.01) along with kinematic modifications including
      greater hip and knee excursion. When the mass was removed, these adaptations were
      maintained 20 min later. INTERPRETATION: Preliminary findings suggest that even
      brief gait training using a treadmill with a restrictive weight placed on the
      distal extremity of the non-hemiplegic lower limb can improve laboratory measures
      of gait ability in a sample of stroke subjects. Future studies must evaluate the
      effect of this technique in longer-term locomotor retraining.

PMID- 18325647
TI  - Interactive effects of nitrogen deposition and fire on plant and soil chemistry
      in an alpine heathland.
AB  - The response of alpine heathland vegetation and soil chemistry to N additions of
      0, 10, 20 and 50 kg N ha(-1) year(-1) in combination with simulated accidental
      fire (+/-) was monitored over a 5-year period. N addition caused rapid and
      significant increases in plant tissue N content and N:P and N:K of Calluna
      vulgaris, suggesting increasing phosphorus and potassium limitation of growth.
      Soil C:N declined significantly with N addition, indicating N saturation and
      increasing likelihood of N leakage. Fire further decreased soil C:N and reduced
      potential for sequestration of additional N. This study shows that alpine
      heathlands, which occupy the headwaters of many rivers, have limited potential to
      retain deposited N and may rapidly become N saturated, leaking N into downstream
      communities and surface waters.

PMID- 18325648
TI  - Risk assessment for the amino acids taurine, L-glutamine and L-arginine.
AB  - Taurine, glutamine and arginine are examples of amino acids which have become
      increasingly popular as ingredients in dietary supplements and functional foods
      and beverages. Animal and human clinical research suggests that oral
      supplementation of these amino acids provides additional health and/or
      performance benefits beyond those observed from normal intake of dietary protein.
      The increased consumer awareness and use of these amino acids as ingredients in
      dietary supplements and functional foods warrant a comprehensive review of their
      safety through quantitative risk assessment, and identification of a potential
      safe upper level of intake. The absence of a systematic pattern of adverse
      effects in humans in response to orally administered taurine (Tau), l-glutamine
      (Gln) and l-arginine (Arg) precluded the selection of a no observed adverse
      effect level (NOAEL) or lowest observed adverse effect level (LOAEL). Therefore,
      by definition, the usual approach to risk assessment for identification of a
      tolerable upper level of intake (UL) could not be used. Instead, the newer method
      described as the Observed Safe Level (OSL) or Highest Observed Intake (HOI) was
      utilized. The OSL risk assessments indicate that based on the available published
      human clinical trial data, the evidence for the absence of adverse effects is
      strong for Tau at supplemental intakes up to 3 g/d, Gln at intakes up to 14 g/d
      and Arg at intakes up to 20 g/d, and these levels are identified as the
      respective OSLs for normal healthy adults. Although much higher levels of each of
      these amino acids have been tested without adverse effects and may be safe, the
      data for intakes above these levels are not sufficient for a confident conclusion
      of long-term safety, and therefore these values are not selected as the OSLs.

PMID- 18325649
TI  - Poverty and mental illness: fact or fiction? A commentary on Das, Do, Friedman,
      McKenzie & Scott (65:3, 2007, 467-480).

PMID- 18325650
TI  - 'I don't do like I used to do': a grounded theory approach to conceptualising
      awareness in people with moderate to severe dementia living in long-term care.
AB  - While awareness among people with mild to moderate dementia residing in the
      community has been extensively studied, little evidence has been presented
      regarding the extent to which people with moderate to severe dementia living in
      residential care show awareness of their own situation and functioning. The
      present study aimed to explore how differing degrees of awareness are manifested
      in the conversations and interactions of people with dementia living in
      residential care settings, and to identify theoretical and practical
      implications. Transcripts of 304 conversations with 80 individuals with dementia
      living in residential care homes in England and Wales were analysed using a
      grounded theory approach. All 80 participants demonstrated a degree of retained
      awareness, and there was considerable evidence of retained awareness throughout
      the conversations, expressed in relation to the three domains of self,
      relationship, and the environmental context. Two-thirds of participants also
      demonstrated at least one instance of unawareness, although demonstrations of
      retained awareness outweighed indications of unawareness. Unawareness was evident
      in relation to appraisal of functioning and the meaning ascribed to the
      situation. A grounded theory model of awareness in people with moderate to severe
      dementia who still communicate verbally proposes that demonstration of awareness
      involves a set of analytic and behavioural processes, a scope or timescale, and a
      focus. Awareness is demonstrated in relation to a given focus and scope through
      the involvement of cognitive processes of varying degrees of complexity, ranging
      from registering through appraising and interpreting to reflection. Unawareness
      may be demonstrated in relation to some elements of process, focus or scope,
      while other aspects remain unaffected. Understanding more about the capacity for
      retained awareness and the specific ways in which awareness can be compromised
      may assist care staff in responding effectively to residents' needs.

PMID- 18325651
TI  - Beefing up with the Chans: evidence for the effects of relative income and income
      inequality on health from the China Health and Nutrition Survey.
AB  - A great deal of research has examined the hypothesis that the well-being of
      individuals is shaped not just by the absolute level of resources available to
      them but also the level of resources available to them relative to others in
      their cohort or community. Several causal pathways have been hypothesized to
      explain associations between relative social position and health. For example,
      greater community income could increase the overall availability of health care
      in a community or decrease the availability for people for any given level of
      individual income. Relative social position could also create stress, resulting
      in adverse health outcomes through increased hypertension and other pathways. We
      explore yet another pathway by which relative social position may affect health.
      Specifically, to the extent that norms about physical appearance might be shaped
      by one's observations of others, we examine whether obesity might constitute
      another physiologic pathway by which community attributes could influence aspects
      of individual health, such as hypertension. We examine this hypothesis in rural
      China, where income often limits food intake so that, if community norms are an
      important determinant of individual obesity, higher community income could
      increase the obesity rate in a community and therefore change norms about
      obesity. These norms, in turn, could increase individuals' chances of being obese
      given their income. To test this hypothesis, we use multilevel linear probability
      models to examine the relationship between ecologic factors, i.e., relative
      income and income inequality, and health risk factors, i.e., obesity and
      hypertension among a sample of Chinese adults interviewed in four waves over 9
      years. The results suggest that, among rural Chinese residents, increasing
      community average income and income inequality are positively associated with
      both obesity and hypertension. However, the effect of relative income on
      hypertension is not accounted for by increases in obesity. We did not find a
      strong relationship between socioeconomic conditions and the health risk factors
      among urban residents, where norms might be likely to be less strongly influenced
      by local attributes. Hence, the present study provides evidence supporting the
      hypothesis that relative income and income inequality affect obesity and
      hypertension, but no evidence that the effects on hypertension operated through
      effects on obesity.

PMID- 18325652
TI  - Antidepressant response and intolerance to SSRI is not influenced by G-protein
      beta3 subunit gene C825T polymorphism in Japanese major depressive patients.
AB  - The G-protein beta3 subunit (GNB3) gene is a key modulator of signal transduction
      and is a major candidate for SSRIs response. The aim of the present study is to
      test a possible effect of the C825T polymorphism on the antidepressant response
      and intolerance to selective serotonin reuptake inhibitors (SSRIs) in 146
      Japanese samples with major depression treated with paroxetine or fluvoxamine for
      6 weeks. The severity of depression symptom was assessed using the 21-item
      Hamilton Rating Scale for Depression (HAM-D) and adverse drug reactions were
      evaluated bi-weekly. No association with SSRIs treatment response was observed in
      107 completers also including HAM-D baseline scores, SSRI type or/and 5-HTTLPR
      variants in the model as covariates. Furthermore, no significant association
      could be observed with intolerance to SSRIs in the whole subjects. The result
      suggests that C825T variants of GNB3 cannot play a major role as a predictor of
      treatment response as well as intolerance to SSRIs in Japanese patients with
      major depression.

PMID- 18325653
TI  - Impact of Bacillus thuringiensis toxin Cry1Ab on rumen epithelial cells (REC) - a
      new in vitro model for safety assessment of recombinant food compounds.
AB  - The growing use of genetically modified crops necessitates viable screening
      methods for safety evaluation of recombinant feed, particularly for ruminants. A
      new sheep rumen epithelial cell culture is introduced as an in vitro cell system
      for safety evaluation especially focussing on feed and food compounds. We used
      lactate dehydrogenase (LDH) release, WST-1 conversion, ATP content and caspase
      3/7 activity to evaluate cytotoxicity of Cry1Ab, one of the newly expressed Bt
      proteins in transgene maize. The results were compared to the effects of
      valinomycin, a potassium ionophore known to induce cytotoxic effects on a wide
      range of cells. Whereas no toxicity of Cry1Ab was observed in short as well as in
      long term experiments, even at non-physiological high concentrations, exposure to
      valinomycin induced apoptosis and a significant response of all viability
      parameters after a number of hours. The ATP content and the WST-1 conversion
      reflecting the energy metabolism of the cells appear to be more sensitive
      indicators of valinomycin toxicity than the LDH release, a parameter which
      reflects the membrane integrity. This study presents an in vitro model system,
      that may be useful as a supplementary tool in toxicity screening before testing
      substances on animals in vivo.

PMID- 18325654
TI  - Involvement of oxidative stress-activated JNK signaling in the methamphetamine
      induced cell death of human SH-SY5Y cells.
AB  - Methamphetamine (METH) is one of the most commonly abused drugs that may result
      in neurotoxic damage. Many lines of evidence have revealed that oxidative stress
      plays an important role in METH-induced neurotoxic effects. In a previous study,
      it was demonstrated in human neuroblastoma SH-SY5Y cells that enhanced oxidative
      stress was related to METH-induced apoptosis. To evaluate which of the three
      major mitogen-activated protein (MAP) kinase signaling pathways are involved in
      the process, namely the extracellular signal-related kinases (ERK), the p38 MAP
      kinases (p38) and the Jun-N-terminal kinases (JNK), we performed a time-course
      assessment. This indicated that METH induced an increase in the phosphorylation
      of ERK and JNK, but not of p38. Moreover, a JNK-specific inhibitor, SP600125,
      partially but significantly rescued METH-induced cell death, while PD98059 (an
      ERK kinase inhibitor) and SB203580 (a p38 inhibitor) had no protective effect. We
      also found that vitamin E (Vit E) prevented METH-induced JNK phosporylation and
      SP600125 inhibited METH-induced c-Jun phosphorylation. Furthermore, METH
      activated caspase-3 activity was significantly repressed by Vit E and in SP600125
      treated cells. We suggest that the oxidative stress-activated JNK signaling
      pathway is involved in METH-induced cell death.

PMID- 18325655
TI  - Cortisol dysregulation in school teachers in relation to burnout, vital
      exhaustion, and effort-reward-imbalance.
AB  - We analyzed whether burnout and vital exhaustion or job-related chronic stress is
      associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation in school
      teachers (N=135; 25-63 years; mean age 46.1+/-9.20 years). Participants collected
      seven saliva samples (0, 30, 45, and 60 min after awakening, 11a.m., 3 p.m., 8
      p.m.) on 2 working days, 1 leisure day, and after pre-medication with 0.25mg
      dexamethasone (very low-dose dexamethasone suppression test) to assess basal
      cortisol day profiles and HPA axis negative feedback sensitivity. No associations
      were found between basal cortisol activity and burnout (Maslach burnout
      inventory, teacher burnout scale), vital exhaustion (Appels vital exhaustion
      questionnaire), or any component of Siegrist's effort-reward-imbalance model.
      However, after dexamethasone higher burnout and vital exhaustion and lower reward
      were significantly related to stronger cortisol suppression, pointing to altered
      HPA axis negative feedback sensitivity. Though, all teachers were working and in
      a good health status, burnout/exhaustion as well as facets of the ERI model
      appear to be associated with subtle dysregulation, manifested as heightened HPA
      axis negative feedback although not in basal cortisol day profiles.

PMID- 18325656
TI  - How does reorganization energy change upon protein unfolding? Monitoring the
      structural perturbations in the heme cavity of cytochrome c.
AB  - In several classes of proteins the redox center provides an additional intrinsic
      biophysical probe that could be used to study the protein structure and function.
      In present report reorganization energy (lambda, as a parameter describing
      electron transfer properties) was used to study the protein structural changes
      around the heme prosthetic group in cytochrome c (cyt c). We attempted to monitor
      the value of this parameter upon the unfolding process of cyt c by urea, during
      which it was increased sigmoidally from about 0.52 to 0.82 eV for native and
      unfold protein, respectively. Results indicate that by structural changes in the
      heme site, lambda provides a complementary tool for following the unfolding
      process. Assuming a reversible two-state model for cyt c unfolding, Delta G(H2O),
      Cm and m values were determined to be 8.32+/-0.7 kcal mol(-1), 1.53+/-0.19
      kcalmol(-1)M(-1) and 5.03 M, respectively.

PMID- 18325657
TI  - Age and bladder outlet obstruction are independently associated with detrusor
      overactivity in patients with benign prostatic hyperplasia.
AB  - BACKGROUND: Detrusor overactivity is one known cause of lower urinary tract
      symptoms and has been linked to bladder storage symptoms (urgency, frequency, or
      urge incontinence). OBJECTIVE: To determine clinical and urodynamic parameters
      associated with detrusor overactivity in patients with suspected benign prostatic
      hyperplasia. DESIGN, SETTING, AND PARTICIPANTS: During 1993-2003, urodynamic
      investigations were performed in patients aged 40 yr or older and with lower
      urinary tract symptoms, benign prostatic enlargement, and/or suspicion of bladder
      outlet obstruction (maximum flow rate < 15 ml/s or postvoid residual urine > 50
      ml). MEASUREMENTS: Detrusor overactivity was defined according to the new
      International Continence Society classification (2002) as involuntary detrusor
      contractions during cystometry, which may be spontaneous or provoked, regardless
      of amplitude. The Schafer algorithm was used to determine bladder outlet
      obstruction. RESULTS: In total, 1418 men were investigated (median age: 63 yr) of
      whom 864 men (60.9%) had detrusor overactivity. In univariate analysis, men with
      detrusor overactivity were significantly older, more obstructed, had larger
      prostates, higher irritative International Prostate Symptoms Score subscores, a
      lower voiding volume at free uroflowmetry, and a lower bladder capacity at
      cystometry. The prevalence of detrusor overactivity rose continuously with
      increasing bladder outlet obstruction grade. Multivariate analysis showed that
      only age and bladder outlet obstruction grade were independently associated with
      detrusor overactivity. After age adjustment, the odds ratios of detrusor
      overactivity compared to Schafer class 0 were 1.2 for class I, 1.4 for class II,
      1.9 for class III, 2.5 for class IV, 3.4 for class V, and 4.7 for class VI.
      CONCLUSIONS: In patients with clinical benign prostatic hyperplasia, detrusor
      overactivity is independently associated with age and bladder outlet obstruction.
      The probability of detrusor overactivity rises with increasing age and bladder
      outlet obstruction grade.

PMID- 18325658
TI  - Non-mammalian vertebrate models and the endocannabinoid system: relationships
      with gonadotropin-releasing hormone.
AB  - Endocannabinoids, via cannabinoid receptors (CB1 and CB2), affect reproductive
      functions at both local and central level. Due to the high complexity of the
      endocannabinoid system, to the widespread distribution outside the nervous system
      and to the high degree of evolutionary conservation, a deep CB1 molecular
      characterization among species may be useful to elucidate the activity of
      endocannabinoids at multiple levels. In this review we report CB1
      characterization in non-mammalian animal models and, in particular, in the anuran
      amphibian, the frog, Rana esculenta; we also describe its expression during the
      annual sexual cycle. Moreover, since reproductive functions are under control of
      gonadotropin releasing hormone (GnRH), cb1 mRNA and protein expression profile in
      the forebrain has been compared to those of GnRH-I, the mammalian form primarily
      involved in gonadotropin release.

PMID- 18325659
TI  - Role of TRPV1 receptors in descending modulation of pain.
AB  - Transient receptor potential vanilloid type 1 (TRPV1) receptor is a ligand-gated
      non-selective cation channel activated by heat (>43 degrees C), low pH and
      endogenous lipid molecules such as anandamide, N-arachidonoyl-dopamine, N-acyl
      dopamines and products of lipoxygenases (12- and 15-(S)-HPETE) termed
      endovanilloids. Apart from peripheral primary afferent neurons and dorsal root
      ganglia, TRPV1 receptor is expressed throughout the brain. Recent evidence shows
      that TRPV1 receptor stimulation by endocannabinoids or by capsaicin within the
      periaqueductal grey (PAG) leads to analgesia and this effect is associated with
      glutamate increase and the activation of OFF cell population in the rostral
      ventromedial medulla (RVM). Activation of the antinociceptive descending pathway
      via TPRV1 receptor stimulation in the PAG may be a novel strategy for producing
      analgesia. This review will summarize the more recent insights into the role of
      TRPV1 receptor within the antinociceptive descending pathway and its possible
      exploitation as a target for novel pain-killer agents.

PMID- 18325660
TI  - The potential use of adult stem cells for the treatment of multiple sclerosis and
      other neurodegenerative disorders.
AB  - No specific treatment exists for patients with multiple sclerosis (MS) who fail
      to respond to conventional immunosuppressive and immunomodulating modalities.
      Furthermore, no method is available for regeneration of existing defect in the
      central nervous system (CNS). The ultimate goals of MS treatment, similarly to
      other autoimmune diseases, are twofold: first, to eliminate self-reactive
      lymphocytes and to prevent de novo development of self-reactivity by induction of
      self-tolerance. Second, attempting regeneration and repair of existing damage. In
      the case of MS, there is a need to stop the ongoing process of inflammation
      against the CNS by self-reactive lymphocytes thus facilitating spontaneous re
      myelinization while in parallel attempt to recover existing neurological deficits
      caused by the autoimmune process resulting in demyelinization. Cell therapy
      stands out as the most rationale approach for neurological regeneration. In the
      absence of clinically applicable approaches involving the use of embryonic stem
      cells, we are investigating the feasibility and efficacy of enriched autologous
      mesenchymal stromal cells (MSC) injected intrathecally and intravenously to
      induce in situ immunomodulation and neuroprotection and possibly facilitate
      repair of the CNS in patients with MS and other neurodegenerative disorders. Our
      preclinical results suggest that bone marrow cells may provide a source of stem
      cells with a potential for migration into inflamed CNS and differentiate into
      cells expressing neuronal and glial cell markers. Based on the preclinical data,
      we are currently evaluating the safety of a similar therapeutic approach in a
      small group of patients with MS and other neurodegenerative diseases.

PMID- 18325661
TI  - Generation of novel monoclonal antibodies and their application for detecting
      ARD1 expression in colorectal cancer.
AB  - Arrest defective 1 (ARD1) is an acetyltransferase involved in cell cycle control
      in yeast. ARD1 interacts with human N-acetyltransferase (NATH) to form a
      functional N-terminal acetyltransferase complex. Recently it had been linked with
      proliferation and apoptosis in mammalian cells, but its function in cancer
      development remains unclear. To evaluate significance of ARD1 expression in human
      colorectal cancer, we generated a panel of monoclonal antibodies (mAbs) with high
      specificity and sensitivity against ARD1. All of the 10 different clones could be
      used in ELISA and Western blot, and clone 10C12, 13G2, and 4D10 can interact with
      ARD1 in eukaryotic cells by immunoprecipitation (IP). Clones of 14D4 and 10C12
      were strongly reacted to ARD1 in immunocytochemistry (ICH) and
      immunohistochemistry (IHC). ARD1 expression was evaluated in human colorectal
      cancer and colitis tissues by immunohistochemical analysis with mAb 14D4. Forty
      one were ARD1-positive in 50 colorectal cancer tissues and only 12 were weak
      positive in the 50 matched normal tissues (P < 0.001). Moreover, ARD1 expression
      was not detectable in 20 cases of colitis tissue (P < 0.001). Furthermore, all of
      the six human colorectal cancer cell lines we examined were also ARD1-positive at
      mRNA and protein levels. Taken together, the novel mAbs against ARD1 we generated
      could be good tools for both basic and clinical studies, and ARD1 could be a
      potential biomarker in colorectal cancer.

PMID- 18325662
TI  - Substrate interactions during anaerobic biodegradation of BTEX by the mixed
      cultures under nitrate reducing conditions.
AB  - The enriched BTEX-degrading bacteria were used to investigate the substrate
      interactions during anaerobic biodegradation of all the possible BTEX binary
      combinations. Beneficial and detrimental substrate interactions were observed in
      comprehensive mixtures of benzene, toluene, ethylbenzene, o-xylene, m-xylene and
      p-xylene. The amendment of toluene or ethylbenzene could stimulate benzene
      degradation. Lower concentrations of m-xylene would enhance the degradation of
      benzene, whereas degradation of benzene was inhibited with higher concentrations
      of m-xylene. The simultaneous presence of toluene and ethylbenzene could
      stimulate the degradation of each other. The addition of toluene stimulated o
      xylene degradation, whereas the amendment of ethylbenzene inhibited the
      degradation of o-xylene. Lower concentrations of toluene or ethylbenzene would
      enhance the degradation of m-xylene and p-xylene, whereas higher concentrations
      of toluene or ethylbenzene had a slight inhibitory effect on m-xylene and p
      xylene degradation. The amendment of benzene, m-xylene or p-xylene would inhibit
      the degradation of other BTEX compounds. When the concentration of BTEX mixtures
      was over 150 mg/l, the degradation of benzene, o-xylene, m-xylene and p-xylene
      was severely inhibited.

PMID- 18325663
TI  - A new scheme for biomonitoring heavy metal concentrations in semi-natural
      wetlands.
AB  - This work introduces a semi-natural wetland biomonitoring framework for heavy
      metal concentrations based on a robust dynamic integration between biological
      assemblages and relevant biosensors. The cooperative/synergistic scheme developed
      minimizes uncertainty and monitoring costs and increases reliability of pollution
      control and abatement. Attention is given to establishing a fully functioning and
      reliable network approach for monitoring inflows and achieving dose-response
      relations and calibration of biomonitoring species. The biomonitoring network
      initially consists of both, biosensors and species, as a validation phase in each
      wetland of the surveillance area; once the species monitoring efficiency is
      verified by the biosensors, the biosensor network moves to the next wetland and
      so on, following a circular pattern until all area wetlands have a fully
      functional natural monitoring scheme. By means of species recalibration with
      periodic revisiting of the biosensors, the scheme progressively reaches a quasi
      steady-state (including seasonality), thus ensuring reliability and robustness.
      This framework, currently pilot-tested in Voiotia, Greece, for assessing chromium
      levels, has been built to cover short-, medium- and long-term monitoring
      requirements. The results gathered so far, support the employment of the proposed
      scheme in heavy metal monitoring, and, further, arise the need for volunteer
      involvement to achieve long-term viability.

PMID- 18325664
TI  - Flattened cortical maps of cerebral function in the rat: a region-of-interest
      approach to data sampling, analysis and display.
AB  - We describe a method for the measurement, analysis and display of cerebral
      cortical data obtained from coronal brain sections of the adult rat. In this
      method, regions-of-interest (ROI) are selected in the cortical mantle in a
      semiautomated fashion using a radial grid overlay, spaced in 15 degrees intervals
      from the midline. ROI measurements of intensity are mapped on a flattened two
      dimensional surface. Topographic maps of statistical significance at each ROI
      allow for the rapid viewing of group differences. Cortical z-scores are displayed
      with the boundaries of brain regions defined according to a standard atlas of the
      rat brain. This method and accompanying software implementation (Matlab, Labview)
      allow for compact data display in a variety of autoradiographic and histologic
      studies of the structure and function of the rat brain.

PMID- 18325665
TI  - Bone marrow stromal cells can be delivered to the site of traumatic brain injury
      via intrathecal transplantation in rabbits.
AB  - Recent studies suggest that bone marrow stromal cells (BMSCs) are promising
      grafts for treatment of traumatic brain injury (TBI). Neural precursor cells
      (NPCs) have been detected in the site of cervical cord injury following
      intrathecal injection by lumbar puncture. So, this study is designed to determine
      whether BMSCs (after intrathecal administration by lumbar puncture) could also
      migrate to the TBI site. The cells were cultured in vitro and transfected with
      adenovirus green fluorescent protein (Ad-GFP), and then transplanted
      intrathecally or intravenously into an autologous rabbit model of TBI. The
      labeled, grafted cells were identified in the injured cerebral tissue using
      fluorescence microscopy. Results showed that the intrathecal protocol was more
      efficient than the intravenous one. And motor dysfunction was improved after
      autologous transplantation of BMSCs. This study suggests another attractive
      minimally invasive option for treating TBI.

PMID- 18325666
TI  - Primary motor cortex activation by transcranial direct current stimulation in the
      human brain.
AB  - Transcranial direct current stimulation (tDCS) can modulate motor cortex
      excitability in the human brain. We attempted to demonstrate the cortical
      stimulation effect of tDCS on the primary motor cortex (M1) using functional MRI
      (fMRI). An fMRI study was performed for 11 right-handed healthy subjects at 1.5
      T. Anodal tDCS was applied to the scalp over the central knob of the M1 in the
      left hemisphere. A constant current with an intensity of 1.0 mA was applied. The
      total fMRI paradigm consisted of three sessions with a 5-min resting period
      between each session. Each session consisted of five successive phases (resting
      tDCS-tDCS-tDCS-tDCS), and each of the phases was performed for 21s. Our findings
      revealed that no cortical activation was detected in any of the stimulation
      phases except the fourth tDCS phase. In the result of group analysis for the
      fourth tDCS phase, the average map indicated that the central knob of the left
      primary motor cortex was activated. In addition, there were activations on the
      left supplementary motor cortex and the right posterior parietal cortex. We
      demonstrated that tDCS has a direct stimulation effect on the underlying cortex.
      It seems that tDCS is a useful modality for stimulating a target cortical region.

PMID- 18325667
TI  - Association between genetic polymorphism of GSTT1 and depression score in
      individuals chronically exposed to natural sour gas.
AB  - In order to investigate the association between effects of genetic polymorphisms
      of GSTT1 and GSTM1 and depression score of individuals chronically exposed to
      natural sour gas containing sulfur compounds, the present cross-sectional study
      was done. The study was performed on 124 healthy females living in the polluted
      area of Masjid-i-Sulaiman (MIS; Khozestan province, southwest of Iran). The GSTT1
      and GSTM1 genotypes were determined using a polymerase chain reaction (PCR)-based
      method. Depression and hopelessness scores were determined by means of Beck's
      depression inventory (BDI) and Beck's hopelessness scale (BHS), respectively. The
      BHS score was positively correlated to the depression score (beta=0.687,
      t=10.474, p<0.001). The GSTT1 active genotype decreased the BDI score (beta=
      0.161, t=-2.451, p=0.016). Polymorphism of GSTM1 may not be a good predictive
      factor for BDI (beta=-0.056, t=-0.857, p=0.393). There is no evidence for
      additive effect of GSTM1 and GSTT1 polymorphisms on BDI score. It is supposed
      that chronic exposure to natural sour gas may positively associated with DNA
      strand breaks and apoptosis in brain, especially in GSTT1 null genotype persons;
      finally living in the contaminated areas of MIS is associated with high BDI
      score.

PMID- 18325668
TI  - Changes in electroencephalogram and heart rate during treadmill exercise in the
      rat.
AB  - To explore whether exercise is related to electroencephalogram (EEG) and heart
      rate changes, continuous EEG power spectral analysis was performed on rats during
      treadmill exercise. Compared with before exercise, treadmill exercise resulted
      promptly in a higher mean power frequency and theta (6-10 Hz) power of the EEG,
      but lower delta (0.5-4 Hz) power of the EEG together with a lower R-R interval of
      electrocardiogram. Such changes quickly reversed when the treadmill exercise was
      stopped. We conclude that the cerebral cortex activates along with the autonomic
      system during running. Our methodology offers an efficient way to study the
      interaction of cerebral and brain stem functions with exercise in the rat.

PMID- 18325669
TI  - Increased oscillatory theta activation evoked by violent digital game events.
AB  - The authors examined electroencephalographic (EEG) oscillatory responses to two
      violent events, the player character wounding and killing an opponent character
      with a gun, in the digital game James Bond 007: NightFire. EEG was recorded from
      25 (16 male) right-handed healthy young adults. EEG data were segmented into one
      1-s baseline epoch before each event and two 1-s epochs after event onset. Power
      estimates (microV(2)) were derived with the fast Fourier transform (FFT) for each
      artefact free event. Both of the studied events evoked increased occipital theta
      (4-6Hz) responses as compared to the pre-event baseline. The wounding event
      evoked also increased occipital high theta (6-8Hz) response and the killing event
      evoked low alpha (8-10Hz) asymmetry over the central electrodes, both relative to
      the pre-event baseline. The results are discussed in light of facial
      electromyographic and electrodermal activity responses evoked by these same
      events, and it is suggested that the reported EEG responses may be attributable
      to affective processes related to these violent game events.

PMID- 18325670
TI  - Association between the brain-derived neurotrophic factor Val66Met polymorphism
      and brain morphology in a Japanese sample of schizophrenia and healthy
      comparisons.
AB  - Magnetic resonance imaging was used to investigate the relation between the brain
      derived neurotrophic factor (BDNF) Val66Met polymorphism and volumetric
      measurements for the medial temporal lobe structures (amygdala, hippocampus, and
      parahippocampal gyrus) and prefrontal sub-regions (the superior frontal gyrus,
      middle frontal gyrus, inferior frontal gyrus, ventral medial prefrontal cortex,
      orbitofrontal cortex, and straight gyrus) in a Japanese sample of 33
      schizophrenia patients and 29 healthy subjects. For the controls, the Met
      carriers had significantly smaller parahippocampal and left superior frontal gyri
      than the Val homozygotes. The schizophrenia patients carrying the Met allele had
      a significantly smaller right parahippocampal gyrus than those with the Val/Val
      genotype, but the genotype did not affect the prefrontal regions in schizophrenia
      patients. These findings might reflect different genotypic effects of BDNF on
      brain morphology in schizophrenia patients and healthy controls, implicating the
      possible role of the brain morphology as an endophenotype for future genetic
      studies in schizophrenia.

PMID- 18325671
TI  - Directional colour encoding of the human thalamus by diffusion tensor imaging.
AB  - The potential of diffusion tensor imaging (DTI) in brain imaging in terms of the
      in vivo mapping of neuroanatomy is generally accepted. Mostly, analyses of deep
      brain structures were based on complex methodical backgrounds. In the present
      study, the delineation of groups of thalamic nuclei with similar projection
      characteristics was investigated in healthy human subjects using a novel
      differentiated colour encoding approach of DTI data without the use of
      statistical calculations. With the application of this directional colour
      encoding of the longest eigenvector of every voxel-specific tensor, at least
      three functional groups in the thalamus with different projection directions
      could be differentiated. The method displayed, furthermore, a high symmetry and
      stability in the analysis of the individual subjects. In summary, substantial
      neuroanatomical information can be gained for deep subcortical gray matter
      structures such as the thalamus with an improved detection and directional
      differentiation of voxel-specific tensors.

PMID- 18325672
TI  - Trinucleotide expansions in the SCA7 gene in a large family with spinocerebellar
      ataxia and craniocervical dystonia.
AB  - Spinocerebellar ataxia type 7 is a rare autosomal dominant cerebellar ataxia
      (ADCA). Herein, we describe the molecular and clinical findings in patients
      within six generations of a large Chinese family with spinocerebellar ataxia. To
      identify the genetic cause(s), 4 affected patients and 26 asymptomatic relatives
      were recruited for the study. Molecular screening of the SCA1 and SCA7 genes was
      carried out by subcloning and direct PCR-sequencing methods. Both neurological
      and ophthalmic examinations were performed to investigate the clinical
      characteristics of the disease. The patients had typical cerebellar ataxia,
      achromatopsia and macular degeneration, and displayed a rare phenotype
      manifesting as a combination of cerebellar ataxia and craniocervical dystonia.
      Mutational analysis of the SCA7 genes demonstrated expanded CAG-repeats in the
      four patients. In conclusion, we identified expanded CAG-repeats in the SCA7 gene
      within members of a large Chinese family with spinocerebellar ataxia. The defined
      phenotypic characteristics of the patients may be helpful for clinical diagnosis
      and genetic typing of new patients.

PMID- 18325673
TI  - Effects of varied doses of psilocybin on time interval reproduction in human
      subjects.
AB  - Action of a hallucinogenic substance, psilocybin, on internal time representation
      was investigated in two double-blind, placebo-controlled studies: Experiment 1
      with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very
      low dose. The task consisted in repeated reproductions of time intervals in the
      range from 1.5 to 5s. The effects were assessed by parameter kappa of the 'dual
      klepsydra' model of internal time representation, fitted to individual response
      data and intra-individually normalized with respect to initial values. The
      estimates kappa were in the same order of magnitude as in earlier studies. In
      both experiments, kappa was significantly increased by psilocybin at 90 min from
      the drug intake, indicating a higher loss rate of the internal duration
      representation. These findings are tentatively linked to qualitative alterations
      of subjective time in altered states of consciousness.

PMID- 18325674
TI  - Effects of mood on pain responses and pain tolerance: an experimental study in
      chronic back pain patients.
AB  - Although chronic pain and depression commonly co-occur, causal relationships have
      yet to be established. A reciprocal relationship, with depression increasing pain
      and vice versa, is most frequently suggested, but experimental evidence is needed
      to validate such a view. The most straightforward approach would be a
      demonstration that increasing or decreasing depressed mood predictably modifies
      pain responses. The current experiment tested whether experimentally induced
      depressed and happy mood have differential effects on pain ratings and tolerance
      in 55 patients suffering from chronic back pain. Participants were randomly
      assigned to depressed, neutral (control) or elated mood induction conditions.
      They completed a physically passive baseline task prior to receiving mood
      induction, then a clinically relevant physically active task (holding a heavy
      bag) to elicit pain responses and tolerance. Measures were taken immediately
      after the baseline task and immediately after the mood induction to assess the
      changes in mood, pain ratings and tolerance before and after the experimental
      manipulation. Results indicate that the induction of depressed mood resulted in
      significantly higher pain ratings at rest and lower pain tolerance, whilst
      induced happy mood resulted in significantly lower pain ratings at rest and
      greater pain tolerance. Correlations between changes in mood on the one hand and
      changes in pain response and pain tolerance on the other hand were consistent
      with these findings. It is concluded that, in chronic back pain patients,
      experimentally induced negative mood increases self-reported pain and decreases
      tolerance for a pain-relevant task, with positive mood having the opposite
      effect.

PMID- 18325675
TI  - The efficacy of an augmented virtual reality system to alleviate pain in children
      undergoing burns dressing changes: a randomised controlled trial.
AB  - In children, the pain and anxiety associated with acute burn dressing changes can
      be severe, with drug treatment alone frequently proving to be inadequate. Virtual
      reality (VR) systems have been successfully trialled in limited numbers of adult
      and paediatric burn patients. Augmented reality (AR) differs from VR in that it
      overlays virtual images onto the physical world, instead of creating a complete
      virtual world. This prospective randomised controlled trial investigated the use
      of AR as an adjunct to analgesia and sedation in children with acute burns. Forty
      two children (30 male and 12 female), with an age range of 3-14 years (median age
      9 years) and a total burn surface area ranging from 1 to 16% were randomised into
      a treatment (AR) arm and a control (basic cognitive therapy) arm after
      administration of analgesia and/or sedation. Pain scores, pulse rates (PR),
      respiratory rates (RR) and oxygen saturations (SaO2) were recorded pre
      procedurally, at 10 min intervals and post-procedurally. Parents were also asked
      to grade their child's overall pain score for the dressing change. Mean pain
      scores were significantly lower (p=0.0060) in the AR group compared to the
      control group, as were parental pain assessment scores (p=0.015). Respiratory and
      pulse rates showed significant changes over time within groups, however, these
      were not significantly different between the two study groups. Oxygen saturation
      did not differ significantly over time or between the two study groups. This
      trial shows that augmented reality is a useful adjunct to pharmacological
      analgesia.

PMID- 18325676
TI  - Naltrexone for the management of post-burn pruritus: A preliminary report.
AB  - Severe pruritus after burn continues to be a clinical challenge that is
      inadequately addressed by traditional therapies. The success of naltrexone, an
      opioid antagonist, in treating pruritus in other patient populations, supported
      the concept that it may also be effective in burn survivors. Thus, burn patients
      who were dissatisfied with itch relief obtained after a course of traditional
      therapy were offered naltrexone. Of the 15 subjects included in this case series,
      2 discontinued treatment because of side-effects. Of the remaining 13, 72%
      reported that they were satisfied with the itch relief provided by naltrexone,
      69% were able to decrease or stop taking other medications to reduce itch, 85%
      would recommend it to other burn patients, and 62% divulged that it improved
      their quality of life. A sub-group (n=8) completed the French-Canadian version of
      the Questionnaire for Pruritus Assessment before and after a 2-week course of
      naltrexone treatment. Comparisons of individual responses before and after
      naltrexone treatment revealed that the affective impact of itch appeared to be
      less burdensome. The majority reported either a reduction or no change in the
      frequency of itch experienced. All reported either a decrease or no change in the
      duration of itch experienced after naltrexone treatment. All items that
      previously increased itch were less likely to affect itch or there was no change,
      except with fatigue, physical effort, sweating and eating. There was a
      statistically significant reduction in their visual analogue scale intensity
      ratings of itch "at its worst". Thus, naltrexone positively impacted the itch
      experienced by burn patients in association with a high percentage of patient
      satisfaction. Further controlled trials are recommended.

PMID- 18325677
TI  - Acticoat: a critique of application.

PMID- 18325678
TI  - Effects of mu, kappa, and delta opioid receptor agonists on the function of
      hypothalamic-pituitary-adrenal axis in monkeys.
AB  - Opioids can modulate neuroendocrine function. Less is known about the involvement
      of opioid receptor subtypes in the stimulatory effects of opioids on the primate
      hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to
      investigate the stimulatory effects of opioids selective for each receptor
      subtype on plasma adrenocorticotropic hormone (ACTH) and cortisol levels in both
      male and female monkeys. The blood collection procedure was conducted in home
      caged and unanesthetized rhesus monkeys that showed low and stable basal ACTH and
      cortisol levels. Three opioid receptor agonists, fentanyl, U-50488H, and SNC80,
      were used in behaviorally active doses; they are highly selective for mu, kappa,
      and delta opioid receptors, respectively. Plasma samples were collected at
      multiple time points before and after IV administration of each compound and were
      quantified by radioimmunoassay. Neither fentanyl (0.0003-0.02mg/kg) nor SNC80
      (0.03-0.3mg/kg) changed either ACTH or cortisol basal levels. In contrast, U
      50488H (0.01-1mg/kg) dose-dependently stimulated ACTH and cortisol release in
      both male and female monkeys. Importantly, the stimulatory effects of U-50488H on
      the secretion of ACTH were blocked by a selective kappa opioid receptor
      antagonist, nor-Binaltorphimine. The antagonist effect of nor-binaltorphimine
      lasted up to 20 weeks. These results indicate that only synthetic kappa, but not
      mu or delta opioid receptor agonists stimulate HPA axis activity after acute
      administration in primates.

PMID- 18325679
TI  - Phase I-II study of intraoperative radiation therapy (IORT) after radical
      prostatectomy for prostate cancer.
AB  - PURPOSE: Recent studies have suggested an alpha/beta ratio in prostate cancer of
      1.5-3 Gy, which is lower than that assumed for late-responsive normal tissues.
      Therefore the administration of a single, intraoperative dose of irradiation
      should represent a convenient irradiation modality in prostate cancer. MATERIALS
      AND METHODS: Between February 2002 and June 2004, 34 patients with localized
      prostate cancer with only one risk factor (Gleason score > or =7, Clinical Stage
      [cT] > or =2c, or prostate-specific antigen [PSA] of 11-20 ng/mL) and without
      clinical evidence of lymph node metastases were treated with radical
      prostatectomy (RP) and intraoperative radiotherapy on the tumor bed. A dose
      finding procedure based on the Fibonacci method was employed. Dose levels of 16,
      18, and 20 Gy were selected, which are biologically equivalent to total doses of
      about 60-80 Gy administered with conventional fractionation, using an alpha/beta
      ratio value of 3. RESULTS: At a median follow-up of 41 months, 24 (71%) patients
      were alive with an undetectable PSA value. No patients died from disease, whereas
      2 patients died from other malignancies. Locoregional failures were detected in 3
      (9%) patients, 2 in the prostate bed and 1 in the common iliac node chain outside
      the radiation field. A PSA rise without local or distant disease was observed in
      7 (21%) cases. The overall 3-year biochemical progression-free survival rate was
      77.3%. CONCLUSIONS: Our dose-finding study demonstrated the feasibility of
      intraoperative radiotherapy in prostate cancer also at the highest administered
      dose.

PMID- 18325680
TI  - Health-related quality of life 2 years after treatment with radical
      prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients
      with clinically localized prostate cancer.
AB  - PURPOSE: To compare treatment impact on health-related quality of life (HRQL) in
      patients with localized prostate cancer, from before treatment to 2 years after
      the intervention. METHODS AND MATERIALS: This was a longitudinal, prospective
      study of 614 patients with localized prostate cancer treated with radical
      prostatectomy (134), three-dimensional external conformal radiotherapy (205), and
      brachytherapy (275). The HRQL questionnaires administered before and after
      treatment (months 1, 3, 6, 12, and 24) were the Medical Outcomes Study 36-Item
      Short Form, the Functional Assessment of Cancer Therapy (General and Prostate
      Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American
      Urological Association Symptom Index. Differences between groups were tested by
      analysis of variance and within-group changes by univariate repeated-measures
      analysis of variance. Generalized estimating equations (GEE) models were
      constructed to assess between-group differences in HRQL at 2 years of follow-up
      after adjusting for clinical variables. RESULTS: In each treatment group, HRQL
      initially deteriorated after treatment with subsequent partial recovery. However,
      some dimension scores were still significantly lower after 2 years of treatment.
      The GEE models showed that, compared with the brachytherapy group, radical
      prostatectomy patients had worse EPIC sexual summary and urinary incontinence
      scores (-20.4 and -14.1; p < 0.001), and external radiotherapy patients had worse
      EPIC bowel, sexual, and hormonal summary scores (-3.55, -5.24, and -1.94; p <
      0.05). Prostatectomy patients had significantly better EPIC urinary irritation
      scores than brachytherapy patients (+4.16; p < 0.001). CONCLUSIONS: Relevant
      differences between treatment groups persisted after 2 years of follow-up.
      Radical prostatectomy had a considerable negative effect on sexual functioning
      and urinary continence. Three-dimensional conformal radiotherapy had a moderate
      negative impact on bowel functioning, and brachytherapy caused moderate urinary
      irritation. These results provide relevant information for clinical decision
      making.

PMID- 18325681
TI  - Proton radiotherapy for childhood ependymoma: initial clinical outcomes and dose
      comparisons.
AB  - PURPOSE: To report preliminary clinical outcomes for pediatric patients treated
      with proton beam radiation for intracranial ependymoma and compare the dose
      distributions of intensity-modulated radiation therapy with photons (IMRT), three
      dimensional conformal proton radiation, and intensity-modulated proton radiation
      therapy (IMPT) for representative patients. METHODS AND MATERIALS: All children
      with intracranial ependymoma confined to the supratentorial or infratentorial
      brain treated at the Francis H. Burr Proton Facility and Harvard Cyclotron
      between November 2000 and March 2006 were included in this study. Seventeen
      patients were treated with protons. Proton, IMRT, and IMPT plans were generated
      with similar clinical constraints for representative infratentorial and
      supratentorial ependymoma cases. Tumor and normal tissue dose-volume histograms
      were calculated and compared. RESULTS: At a median follow-up of 26 months from
      the start date of radiation therapy, local control, progression-free survival,
      and overall survival rates were 86%, 80%, and 89%, respectively. Subtotal
      resection was significantly associated with decreased local control (p = 0.016).
      Similar tumor volume coverage was achieved with IMPT, proton therapy, and IMRT.
      Substantial normal tissue sparing was seen with proton therapy compared with
      IMRT. Use of IMPT will allow for additional sparing of some critical structures.
      CONCLUSIONS: Preliminary disease control with proton therapy compares favorably
      with the literature. Dosimetric comparisons show the advantage of proton
      radiation compared with IMRT in the treatment of ependymoma. Further sparing of
      normal structures appears possible with IMPT. Superior dose distributions were
      accomplished with fewer beam angles with the use of protons and IMPT.

PMID- 18325682
TI  - A new isoxazol from Glehnia littoralis.
AB  - A new isoxazol derivative, 9,9a-dihydro-naphtho [2, 3-c] isoxazol-3(1H)-one
      (Naphthisoxazol A) (1, Fig. 1) was isolated from the roots of the traditional
      Chinese medicine Glehnia littoralis. The structure has been elucidated on the
      basis of MS and extensive NMR analysis.

PMID- 18325683
TI  - Preliminary evaluation of anti-pyretic and anti-ulcerogenic activities of Sida
      cordifolia methanolic extract.
AB  - The anti-pyretic and anti-ulcerogenic properties of methanolic extract of Sida
      cordifolia aerial parts (MESC) were investigated in rats. Oral dose of 500 mg/kg
      MESC significantly reduced pyrexia induced by TAB vaccine. MESC exhibited
      significant anti-ulcerogenic effect against aspirin and ethanol induced damage.
      Both these properties were comparable to the reference drugs.

PMID- 18325684
TI  - Lignans and sesquiterpenoids from Lactuca sibirica.
AB  - From aerial parts of Lactuca sibirica, two new and one known furofuran lignans
      were isolated, together with four known lactucin-like guaianolides. On the basis
      of spectral data, the new lignans were characterized as acylated glucopyranosides
      of 4alpha, 8alpha-dihydroxypinoresinol.

PMID- 18325685
TI  - New antibacterial triterpenoid saponin from Lactuca scariola.
AB  - A new antibacterial triterpenoid saponin, 3beta-O-[alpha-L-rhamnopyranosyl]-30
      norolean-12,19-diene-28-oic acid 28-O-[beta-D-glucopyranosyl-(1-->4)-O-beta-D
      galactopyranosyl]-ester (1); has been isolated from the stems of Lactuca
      scariola. Its structure was determined by chemical degradations and spectral
      analysis.

PMID- 18325686
TI  - Antibacterial activity of tannin constituents from Phaseolus vulgaris, Fagoypyrum
      esculentum, Corylus avellana and Juglans nigra.
AB  - Tannins were fractionated from acetonic extract preparations of phenolic
      compounds from Phaseolus vulgaris, Fagoypyrum esculentum, Corylus avellana and
      Juglans nigra. Wide variations in antibacterial activities ranging from MICs of
      62.5 to 500 microg/ml were apparent. Of particular note was a relatively high
      level of activity (62.5 to 125 microg/ml) for all extracts against Listeria
      monocytogenes.

PMID- 18325687
TI  - [Prenatal spontaneous closure of gastroschisis: a paradoxal evolution with poor
      outcome].
AB  - Usually considered as an isolated malformation carrying a rather good postnatal
      prognosis, gastroschisis may however occasionally bear an unfavourable outcome
      despite reassuring ultrasound follow-up. We report on the case of a fetus with
      gastroschisis diagnosed at 13 weeks of gestation followed by a progressive bowel
      absorption and closure of the abdominal defect at 24 weeks, associated with a 10
      to 15mm intra-abdominal bowel tract dilatation. At birth, the infant did not show
      any recognizable ventral wall defect or scar. Surgical exploration was decided
      due to the presence of a high level bowel tract occlusion associated with a
      dilated proximal jejunum on standard abdominal X-ray radiograph. Long-segment
      atresia of the midintestine without any possible surgical option was observed.
      The infant died at day 5.

PMID- 18325688
TI  - [How long can we wait at full dilatation. A study of maternal and neonatal
      morbidity related to the duration of the second stage of labour in nulliparous
      women].
AB  - OBJECTIVES: To determine the statistical association, in nulliparous patients,
      between maternal and fetal morbidity and the length of the second stage of
      labour. To precise whether a prolongation of this period of more than 2h may
      results in a dramatic increase of this morbidity. MATERIALS AND METHODS:
      Retrospective cohort study conducted in a level III referral centre between 1
      April 2004 and 30 April 2005, including all nulliparous, term, cephalic, live
      singleton birth without fetal malformation in patients reaching the second stage
      of labour (n=1191). All deliveries were performed without restrictions in the
      length of the second stage of labour in the absence of fetal heart rate
      abnormalities. Maternal and neonatal morbidity were examined according to the
      duration of the second stage of labour with univariate analysis and after
      statistical adjustment with multivariate logistic regression for potential
      confounding variables. RESULTS: Global maternal morbidity ranged from 5.7% after
      1h to 20.4% after more than 3h of full cervical dilatation. After a second stage
      duration of 2h, each additional completed hour resulted in a significant increase
      in global maternal morbidity (OR 1.78; IC 95% [1.59-1.97]), postpartum
      haemorrhage (OR 1.72; IC 95% [1.21-2.23]) and level three or four perineal
      lacerations (OR 1.24; IC 95% [1.7-1.41]). In the same time, caesarean section
      rate (OR 2.09; IC 95% [1.84-2.34]) and operative vaginal deliveries (OR 1.82; IC
      95% [1.59-2.05]) increased significantly. Conversely, our study didn't
      demonstrate any significant association between neonatal morbidity and the length
      of the second stage of labour. CONCLUSION: Our study confirmed the association
      between the duration of the second stage of labour and the increase of maternal
      but not neonatal morbidity. Such an association, predominantly after 3h spend at
      full cervical dilatation, needs to be taken into account and, according to our
      experience, may justify caesarean section.

PMID- 18325689
TI  - [In vitro susceptibility of isolates of Scytalidium spp. from superficial lesions
      against posaconazole].
AB  - Scytalidium spp. is a dematiaceous fungi that has been frequently reported from
      tropical to semi subtropical regions. We distinguish two pathogenic species: S.
      dimidiatum and S. hyalinum which is an homologous non-pigmented mutant of S.
      dimidiatum. This keratinophilic mold may produce superficial disease (skin,
      nails) indistinguishable from dermatophytes. In Martinique, this
      pseudodermatophyte could represent more than 50 % of onychomycosis. Contrary to
      dermatophytes, the clinical response of Scytalidium spp. are typically very poor
      and topical treatment or systemic agents ineffective. To evaluate the potential
      efficacy of the new antifungal agent posaconazole, we tested in vitro 12 clinical
      isolates of Scytalidium spp. (seven S. dimidiatum and five S. hyalinum) against
      posaconazole by Etest method. For the totality of the isolates, the minimum
      inhibitory concentrations (MICs) were low: MICs less or equal to 0.25 microg/ml
      (maximum MICs of 0.25 microg/ml for S. dimidiatum and 0.032 microg/ml for S.
      hyalinum). These in vitro efficacy suggest that the new agent posaconazole may be
      a future alternative treatment.

PMID- 18325690
TI  - [Human genome project: a federator program of genomic medicine].
AB  - The Human Genome Project improves our understanding of the molecular genetics
      basis of the inherited and complex diseases such as diabetes, schizophrenia, and
      cancer. Information from the human genome sequence is essential for several
      antenatal and neonatal screening programmes. The new genomic tools emerging from
      this project have revolutionized biology and medicine and have transformed our
      understanding of health and the provision of healthcare. Its implications pervade
      all areas of medicine, from disease prediction and prevention to the diagnosis
      and treatment of all forms of disease. Increasingly, it will be possible to drive
      predisposition testing into clinical practice, to develop new treatments or to
      adapt available treatments more specifically to an individual's genetic make-up.
      This genomic information should transform the traditional medications that are
      effective for every members of the population to personalized medicine and
      personalized therapy. The pharmacogenomics could give rise to a new generation of
      highly effective drugs that treat causes, not just symptoms.

PMID- 18325691
TI  - [Place of cancer among the risk factors in venous thromboembolism].
AB  - There is a strong association between cancer and venous thromboembolism (VTE).
      Cancer patients have a seven-fold higher risk of developing VTE as compared with
      noncancer patients. In the year following the diagnosis of cancer, 1.6% of
      patients will develop a VTE event. VTE is one of the main cause of death in
      cancer patients, accounting for about 15% of deaths. On the other hand, cancer
      patients represent 15 to 20% of all VTE cases. Beyond classical risk factors for
      VTE, specific risk factors are associated with VTE in cancer patients: tumor
      site, stage, histological type, treatment, duration of the disease. VTE
      occurrence is associated with a poorer outcome in cancer patients: a reduced
      survival is observed in cancer patients with VTE as compared to non-VTE cancer
      patients. This impact of VTE on prognosis varies according to cancer
      characteristics. Conversely, evolution of VTE is different in cancer patients,
      with a higher short-term risk of mortality and a higher risk of recurrences,
      including on anticoagulant treatment, also modulated by cancer characteristics.

PMID- 18325692
TI  - Matching-to-sample by pigeons: the dissociation of comparison choice frequency
      from the probability of reinforcement.
AB  - It has been proposed that comparison choice in matching-to-sample should depend
      on two factors, the relative probability of reinforcement associated with each of
      the comparison stimuli and the conditional probability of each comparison
      stimulus being correct given presentation of one of the samples. DiGian and
      Zentall [DiGian, K.A., Zentall, T.R., 2007. Matching-to-sample in pigeons: in the
      absence of sample memory, sample frequency is a better predictor of comparison
      choice than the probability of reinforcement for comparison choice. Learn Behav.
      35, 242-261] have shown that sample frequency together with the probability of
      choosing each of the comparison stimuli in training can influence comparison
      choice when delays are introduced, when the number of reinforcements associated
      with each of the comparison stimuli is equated. Furthermore, Zentall and Clement
      [Zentall, T.R., Clement, T.S., 2002. Memory mechanisms in pigeons: Evidence of
      base-rate neglect. J. Exp. Psych.: Anim. Behav. Proc. 28, 111-115] have found
      that sample frequency can affect comparison choice when delays are introduced
      independently of the number of choices of each of the comparison stimuli in
      training and the number of reinforcements associated with each of the comparison
      stimuli is equated. In the present experiment we found that the probability of
      choosing each of the comparison stimuli in training can affect comparison choice
      when delays are introduced, independently of sample frequency and when the number
      of reinforcements associated with each of the comparison stimuli is equated.
      Together, these experiments suggest that when the sample is not available, there
      is a partial dissociation between comparison choice and the probability of
      reinforcement associated with each of the comparison stimuli.

PMID- 18325693
TI  - Acute disinhibiting effects of alcohol as a factor in risky driving behavior.
AB  - Automobile crash reports show that up to 40% of fatal crashes in the United
      States involve alcohol and that younger drivers are over-represented. Alcohol use
      among young drivers is associated with impulsive and risky driving behaviors,
      such as speeding, which could contribute to their over-representation in alcohol
      related crash statistics. Recent laboratory studies show that alcohol increases
      impulsive behaviors by impairing the drinker's ability to inhibit inappropriate
      actions and that this effect can be exacerbated in conflict situations where the
      expression and inhibition of behavior are equally motivating. The present study
      tested the hypothesis that this response conflict might also intensify the
      disruptive effects of alcohol on driving performance. Fourteen subjects performed
      a simulated driving and a cued go/no-go task that measured their inhibitory
      control. Conflict was motivated in these tasks by providing equal monetary
      incentives for slow, careful behavior (e.g., slow driving, inhibiting impulses)
      and for quick, abrupt behavior (fast driving, disinhibition). Subjects were
      tested under two alcohol doses (0.65 g/kg and a placebo) that were administered
      twice: when conflict was present and when conflict was absent. Alcohol interacted
      with conflict to impair inhibitory control and to increase risky and impaired
      driving behavior on the drive task. Also, individuals whose inhibitory control
      was most impaired by alcohol displayed the poorest driving performance under the
      drug. The study demonstrates potentially serious disruptions to driving
      performance as a function of alcohol intoxication and response conflict, and
      points to inhibitory control as an important underlying mechanism.

PMID- 18325694
TI  - Transitions to regular smoking and to nicotine dependence in women using
      cannabis.
AB  - BACKGROUND: While there is substantial support in the literature for an increased
      prevalence of cannabis use in cigarette smokers, emerging studies allude to the
      possibility that cannabis users may, in turn, be at significantly elevated risk
      for rapid transitions in their cigarette smoking trajectories. If there is
      evidence in its favor, the increased rates of cigarette smoking in cannabis users
      may prove to be the most significant public health problem associated with
      cannabis use. METHODS: In a sample of 3787 female twins (age range 18-29 years),
      we examined, using discrete-time survival analyses, whether women who reported
      cannabis use were at increased risk for regular cigarette smoking and progression
      to nicotine dependence. RESULTS: After controlling for a large number of
      potential covariates, we found that women who used cannabis were at 4.4 and 2.8
      increased hazards for transitioning from initiation to regular smoking and from
      regular smoking to nicotine dependence, respectively. CONCLUSIONS: Cannabis use
      is associated with transitions to more involved stages of cigarette smoking in
      women. This is a source of public health concern, first due to the high mortality
      associated with cigarette smoking and second, due to the high prevalence of
      cannabis use in the general population.

PMID- 18325695
TI  - Do survivors respond differently when alcohol abuse complicates suicide? Findings
      from the psychological autopsy study in Estonia.
AB  - BACKGROUND: When a person with alcohol use disorder commits suicide, do the
      immediate family members (parents, spouses, and children) react differently from
      the relatives of non-alcohol-related suicides? METHODS: From a series of 427
      psychological autopsies conducted in Estonia we selected 261 cases of suicide
      where the key informants were close relatives. Of the 261 suicides, 148 met the
      DSM-IV criteria for alcohol use disorder (alcohol abuse and alcohol dependence),
      while 113 did not. Unconditional logistic regression was used to estimate the
      association in terms of emotions. RESULTS: The spouses of alcohol misusing
      suicides were significantly more likely to react with anger than those when
      alcohol did not complicate the picture (adjusted OR=3.8, 95% CI=1.4-0.4). The
      children of persons with alcohol use disorder, who committed suicide were less
      likely to feel guilty (adjusted OR=0.2, 95% CI=0.1-0.8) or abandoned (adjusted
      OR=0.2, 95% CI=0.1-0.7) than children of non-alcohol-related suicide victims.
      There were no statistically significant differences in surviving parents'
      emotions. CONCLUSIONS: Alcohol use disorder before suicide changes affective
      responses in spouses and children who are left behind. Bereavement counsellors
      should be alert for complex grief and mourning responses among this group of
      suicide survivors.

PMID- 18325696
TI  - A decisive role of mitochondria in defining rate and intensity of apoptosis
      induction by different alkaloids.
AB  - Sanguinarine, chelerythrine and chelidonine possess prominent apoptotic effects
      towards cancer cells. In this study, we found that sanguinarine and chelerythrine
      induce apoptosis in human CEM T-leukemia cells, and that is accompanied by an
      early increase in cytosolic cytochrome c that precedes caspases-8, -9 and -3
      processing. During apoptosis induction by sanguinarine and chelerythrine,
      reactive oxygen species (ROS) was rapidly generated and DeltaPsi(mt) dissipated,
      while Bax, Bcl-2 and Bcl-X((L/S)) proteins' content in the mitochondrial fraction
      did not change significantly. Caspase-3 activation and DNA fragmentation were
      considerably inhibited by N-acetyl-cysteine (NAC). Chelidonine induced only a
      slight release of cytochrome c (12h), parallel to caspase-3 activation. Effect of
      sanguinarine or chelerythrine towards mitochondria was confirmed by marked
      changes in morphology of this organelle (3h), while chelidonine did not affect
      mitochondria intactness. Sanguinarine or chelerythrine also caused an intensive
      DNA damage in cells in 1h, however a massive increase in number of such impaired
      cells occurred in 6h, while chelidonine induced intensive DNA damage in 15-20%
      cells only in 24h. Thus, our results demonstrated that rapid cytochrome c release
      in CEM T-leukemia cells exposed to sanguinarine or chelerythrine was not
      accompanied by changes in Bax, Bcl-2 and Bcl-X((L/S)) proteins in the
      mitochondrial fraction, and preceded activation of the initiator caspase-8.

PMID- 18325697
TI  - The prohormone 19-norandrostenedione displays selective androgen receptor
      modulator (SARM) like properties after subcutaneous administration.
AB  - One of the most frequently misused steroid precursors (prohormones) is 19
      norandrostenedione (4-estrene-3,17-dione, NOR), which is, after oral
      administration, readily metabolised to nortestosterone, also known as nandrolone
      (durabolin). In this study we have characterised molecular mechanisms of its
      action determined its tissue specific androgenic and anabolic potency after
      subcutaneous (s.c.) administration and investigated potential adverse effects.
      Receptor binding tests demonstrate that NOR binds with high selectivity to the
      AR. The potency of NOR to transactivate androgen receptor (AR) dependent reporter
      gene expression was 10 times lower as compared to dihydrotestosterone (DHT). In
      vivo experiments in orchiectomised rats demonstrated that s.c. treatment with NOR
      resulted only in a stimulation of the weight of the levator ani muscle; the
      prostate and seminal vesicle weights remained completely unaffected. Like
      testosterone, administration of NOR resulted in a stimulation of AR and myostatin
      mRNA expression in the gastrocnemius muscle. NOR does not affect prostate
      proliferation, the liver weight and the expression of the tyrosine
      aminotransferase gene (TAT) in the liver. Summarizing these data it is obvious
      that NOR, if administrated s.c. and in contrast to its metabolite nandrolone,
      highly selectively stimulates the growth of the skeletal muscle but has only weak
      androgenic properties. This observation may have relevance with respect to
      therapeutic aspects but also doping prevention.

PMID- 18325698
TI  - Cyclodextrins as stabilizers for the preparation of drug nanocrystals by the
      emulsion solvent diffusion method.
AB  - Cyclodextrins (CyDs) were employed as protective stabilizers for the preparation
      of surfactant-free nanocrystals of indomethacin (IMC) by using the emulsion
      solvent diffusion method. The effect of changing the type and concentration of
      CyDs on the formation of IMC nanocrystals was investigated. Dispersions were
      freeze-dried to characterize the size, shape, nanoparticle yield, crystallinity,
      and dissolution behavior of the obtained particles. Submicron-sized particles of
      IMC with average diameters in the range of 300-500 nm were obtained by
      incorporating alpha-, beta-, or gamma-CyD in the outer phase of the primary
      emulsions. Quantitative determination demonstrated that more than 80% of IMC was
      recovered as fine particles smaller than 0.8 microm. The powder X-ray diffraction
      (PXRD) and differential scanning calorimetry (DSC) analyses of the freeze-dried
      samples confirmed the polymorphic change of IMC to the meta-stable form. A
      significant enhancement in the dissolution rate of IMC nanocrystals was observed
      when compared to the commercial powder.

PMID- 18325699
TI  - Comparison of 5-aminolevulinic acid-encapsulated liposome versus ethosome for
      skin delivery for photodynamic therapy.
AB  - Topical photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an
      alternative therapy for many non-melanoma skin cancers. The major limitation of
      this therapy, however, is the low permeability of ALA through the stratum corneum
      (SC) of the skin. The objective of the present work was to characterize ethosomes
      containing ALA and to enhance the skin production of protoporphyrin IX (PpIX),
      compared to traditional liposomes. Results showed that the average particle sizes
      of the ethosomes were less than those of liposomes. Moreover, the entrapment
      efficiency of ALA in the ethosome formulations was 8-66% depending on the
      surfactant added. The particle size of the ethosomes was still approximately <200
      nm after 32 days of storage. An in vivo animal study observed the presence of
      PpIX in the skin by confocal laser scanning microscopy (CLSM). The results
      indicated that the penetration ability of ethosomes was greater than that of
      liposomes. The enhancements of all the formulations were ranging from 11- to 15
      fold in contrast to that of control (ALA in an aqueous solution) in terms of PpIX
      intensity. In addition, colorimetry detected no erythema in the irradiated skin.
      The results demonstrated that the enhancement ratio of ethosome formulations did
      not significantly differ between the non-irradiated and irradiated groups except
      for PE/CH/SS, which may have been due to a photobleaching effect of the PDT
      irradiation process.

PMID- 18325700
TI  - Ordered mesoporous silica induces pH-independent supersaturation of the basic low
      solubility compound itraconazole resulting in enhanced transepithelial transport.
AB  - The majority of innovative drug candidates are poorly water soluble and exhibit
      basic properties. This makes them highly dependent on the in vivo encountered
      acid-neutral pH sequence to achieve a sufficient dissolution and thus absorption.
      In this study, we evaluated the pH-independent generation of intraluminally
      induced supersaturation of the model compound itraconazole and its beneficial
      effect on the extent of absorption in the Caco-2 system and the rat in situ
      perfusion system. Local supersaturation was obtained by means of a solvent shift
      method and a novel formulation strategy based on ordered mesoporous silica (OMS)
      as a carrier. In vitro results evidenced that both methods were capable of
      creating a supersaturated state of itraconazole in fasted state simulated
      intestinal fluid (FaSSIF) when no preceding acidic dissolution was simulated. The
      extent of supersaturation exceeded 21.9 and 9.6 during at least 4h for the
      solvent shift method and OMS as a carrier, respectively. As compared to
      saturation conditions (0.09+/-0.01 microg), supersaturation induced by the
      solvent shift method as well as by the use of OMS increased transport across a
      Caco-2 cell monolayer more than 16-fold, resulting in the basolateral appearance
      of 2.20+/-0.29 microg and 1.46+/-0.03 microg itraconazole after 90 min,
      respectively. In the absence of an acid-neutral pH sequence, the performance of
      the marketed product Sporanox was inferior with total transport amounting to
      0.12+/-0.03 microg after 90 min. Enhanced absorption was confirmed in the in situ
      perfusion model where OMS was able to boost total transport of itraconazole after
      60 min from 0.03+/-0.01 nmol cm(-1) to 0.70+/-0.09 nmol cm(-1) compared to
      saturated equilibrium conditions in FaSSIF. The solid dosage form Sporanox again
      failed to achieve a similar extent of absorption enhancement (0.29+/-0.01 nmol
      cm(-1)). These findings suggest that intraluminal supersaturation can be created
      by the use of OMS and that preceding dissolution of basic compounds in the acidic
      medium of the stomach is not required to allow for efficient intestinal
      absorption. The use of OMS appears to be a promising strategy for the delivery of
      especially basic low solubility compounds in patients suffering from
      hypochlorhydria; the pH independency may also result in a more reproducible
      systemic exposure.

PMID- 18325701
TI  - Suppressive effects of Houttuynia cordata Thunb (Saururaceae) extract on Th2
      immune response.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb (Saururaceae), known as
      'E-Sung-Cho' in Korea, has been traditionally used for the treatment of herpes
      simplex, chronic sinusitis, and allergy. AIM OF THE STUDY: To investigate the
      inhibitory activity of Houttuynia cordata Thunb fractions (HcFs) on the T helper
      2 (Th2) immune response, we evaluated the alternation of the release of Th2-type
      cytokines and chemokines such as interleukin (IL)-4 and IL-5, and thymus and
      activation-regulated chemokine (TARC/CCL17). MATERIALS AND METHODS: Ethanol
      fraction was obtained from dried and powdered whole plants of Houttuynia cordata
      Thunb using ethanol. The residue was diluted with water and was then successively
      partitioned with n-hexane, EtOAc and BuOH. HcFs include ethanol, n-hexane, EtOAc,
      BuOH and water fractions. RT-PCR and ELISA were performed to measure mRNA and
      protein expression of cytokines. RESULTS: HcFs inhibited the expression of IL-4
      and IL-5 in response to phorbol 12-myristate 13-acetate (PMA) and calcium
      ionophore (CaI) in Jurkat T cells and the human mast cell line, HMC-1. IL-4- and
      tumor necrosis factor-alpha (TNF-alpha)-induced TARC production was blocked by
      HcFs in skin fibroblast CCD-986sk cells, particularly by the ethanol extract of
      Hc. Stimulants included in PMA, phytohemagglutinin (PHA) and CaI, increased the
      mRNA level of CC chemokine receptor 4 (CCR4), a receptor of TARC, in Jurkat T
      cells, and the ethanol extract of HcF weakly blocked the increased mRNA level.
      However, the stimulants and ethanol extract had no effect on the CCR4 protein
      level. The ethanol extract inhibited TARC-induced migration, as well as basal
      migration of Jurkat T cells. CONCLUSIONS: This study may show the usefulness of
      HcFs in the ethnopharmacological treatment of Th2-mediated or allergic
      inflammation, through the down-regulation of the production of Th2 cytokines and
      TARC, as well as cell migration.

PMID- 18325702
TI  - Cedrelopsis grevei improves endothelial vasodilatation in aged rats through an
      increase of NO participation.
AB  - Cedrelopsis grevei Baill. (Ptaeroxylaceae) trunk bark extract is empirically used
      in Madagascar against several pathologies, from persistent catarrh to
      hypertension. The effect C. grevei extract on age-related changes in systolic
      blood pressure (SBP) and endothelial function was investigated. Rats (90-100 week
      old) received treatment either with C. grevei extract (80 mg kg(-1)) or vehicle
      for 8 weeks. SBP was evaluated by tail-cuff and vascular reactivity and
      endothelial vasodilatation of both aortae and small mesenteric arteries (SMA)
      were assessed by acetylcholine (ACh) in the presence or in the absence of either
      reactive oxygen species (ROS) scavengers superoxide dismutase (SOD) plus catalase
      or the nitric oxide synthase inhibitor, NG-L-arginine methyl ester (L-NAME).
      Plasma nitric oxide (NO) was evaluated by nitrite assay and expressions of eNOS,
      Cu/Zn-, Mn- and EC-SOD were determined by Western Blot. C. grevei administration
      prevented the increase of SBP and improved endothelium-dependent relaxations in
      aortae and SMA from aged rat via increased NO and decreased participation of ROS.
      Furthermore, C. grevei treatment enhanced plasma nitrite content but did not
      modify eNOS, Cu/Zn-, Mn- or EC-SOD expressions in the two arteries studied. These
      results suggest that C. grevei prevents both increased blood pressure and age
      related endothelial dysfunction supporting the empirical use of C. grevei trunk
      bark extract against mild hypertension often associated with aging.

PMID- 18325703
TI  - The presence of Helicobacter pylori in the larynx pathologies.
AB  - OBJECTIVE: The well-known relation of Helicobacter pylori to the MALT-lymphoma
      and gastric carcinoma suggested a possible presence in the laryngeal tissues of
      patients with squamous cell carcinoma of the larynx by using Polymerase Chain
      Reaction (PCR) investigations, and PCR results of benign laryngeal pathologies
      were compared. METHODS: Polymerase Chain Reaction investigations were carried out
      in biopsy samples of 21 patients with squamous cell carcinoma of the larynx and
      of 19 patients with benign laryngeal pathologies like vocal polyp and nodules.
      RESULTS: The PCR results of 17 out of the 21 samples (80.9%) of the patients with
      laryngeal squamous cell carcinoma were positive for H. pylori. Moreover, any
      genomic material of H. pylori was not found in the PCR results of the 19 patients
      with benign laryngeal pathology. It was also determined that the presence of the
      H. pylori in the patients with laryngeal squamous cell carcinoma was
      statistically significant (p=0.0001). In the patients with laryngeal squamous
      cell carcinoma, the comparison of the H. pylori presence within the normal and
      tumoral tissues revealed that 16 normal tissue samples (76.19%) were positive,
      while 9 of the tumoral tissue samples (42.85%) were positive. The ratio of
      bacterial presence in both the normal and tumor tissue samples was 38.09% (8
      patients). The rates of presence revealed a statistically significant difference
      between the normal and tumoral tissue samples (p=0.039). CONCLUSIONS: The
      presence of the genomic material of H. pylori within the laryngeal tissue of
      patients with squamous cell carcinoma of the larynx is a proof of the
      colonization of the bacterium in that tissue. While this may suggest a possible
      relation of the bacterium to the development of laryngeal squamous cell
      carcinoma, no conclusion is possible to be drawn about the mechanism of the
      process.

PMID- 18325704
TI  - Electromagnetic field therapy delays cellular senescence and death by enhancement
      of the heat shock response.
AB  - Hormesis may result when mild repetitive stress increases cellular defense
      against diverse injuries. This process may also extend in vitro cellular
      proliferative life span as well as delay and reverse some of the age-dependent
      changes in both replicative and non-replicative cells. This study evaluated the
      potential hormetic effect of non-thermal repetitive electromagnetic field shock
      (REMFS) and its impact on cellular aging and mortality in primary human T
      lymphocytes and fibroblast cell lines. Unlike previous reports employing
      electromagnetic radiation, this study used a long wave length, low energy, and
      non-thermal REMFS (50MHz/0.5W) for various therapeutic regimens. The primary
      outcomes examined were age-dependent morphological changes in cells over time,
      cellular death prevention, and stimulation of the heat shock response. REMFS
      achieved several biological effects that modified the aging process. REMFS
      extended the total number of population doublings of mouse fibroblasts and
      contributed to youthful morphology of cells near their replicative lifespan.
      REMFS also enhanced cellular defenses of human T cells as reflected in lower cell
      mortality when compared to non-treated T cells. To determine the mechanism of
      REMFS-induced effects, analysis of the cellular heat shock response revealed
      Hsp90 release from the heat shock transcription factor (HSF1). Furthermore, REMFS
      increased HSF1 phosphorylation, enhanced HSF1-DNA binding, and improved Hsp70
      expression relative to non-REMFS-treated cells. These results show that non
      thermal REMFS activates an anti-aging hormetic effect as well as reduces cell
      mortality during lethal stress. Because the REMFS configuration employed in this
      study can potentially be applied to whole body therapy, prospects for translating
      these data into clinical interventions for Alzheimer's disease and other
      degenerative conditions with aging are discussed.

PMID- 18325705
TI  - Clinical and histological findings in nephrogenic systemic fibrosis.
AB  - Nephrogenic systemic fibrosis (NSF) is a relative newcomer to the world of
      medicine. NSF was introduced just over 10 years ago as nephrogenic fibrosing
      dermopathy, but with further investigation, its systemic nature was determined.
      The strict adherence to a definition requiring both clinical and pathological
      concordance has allowed for careful separation of this entity from other
      fibrosing disorders, leading eventually to the realization that gadolinium-based
      contrast agents were closely associated with its onset. As planned prospective
      studies get underway, it is of paramount importance that researchers and
      clinicians realize that NSF remains a very challenging diagnosis, and that both
      clinical and histopathological criteria must be employed to reach the most
      accurate diagnosis possible.

PMID- 18325706
TI  - Evaluation of saliva collection devices for the analysis of steroids, peptides
      and therapeutic drugs.
AB  - The recovery of steroids, peptides and therapeutic drugs from commercial saliva
      collection devices was investigated. Saliva, spiked with defined concentrations
      of the analytes was applied to the Quantisal, three different Salivettes, and the
      Saliva-Collection-System to investigate effects of volume, exposure time and
      temperature on the recovery. Additionally, saliva was collected from healthy
      subjects with the same devices. It was found that glucocorticoids can be measured
      very well from samples obtained with the synthetic fiber Salivettes and the
      Quantisal (80-100%). For androgens, the Quantisal and the Saliva-Collection
      System reached recoveries >80%. The Quantisal and polyester Salivette achieved
      best recoveries (>80%) for peptides. The results for the cotton Salivette were
      extremely poor for melatonin, insulin or IL-8 (<20%). The results from the spike
      recovery experiments were confirmed by samples collected from healthy volunteers.
      For most therapeutic drugs the synthetic fiber Salivettes achieved best
      recoveries of 100+/-10%. Longer exposure of saliva on the collection devices must
      be avoided for most of the analytes, due to their limited stability and increased
      adsorption. In conclusion, no device is suitable for all of the salivary
      compounds. Strict pre-analytical precautions must be considered (e.g. immediate
      processing of the sample) to guarantee reliable analytical results.

PMID- 18325707
TI  - The determination of glycyrrhizic acid in Glycyrrhiza uralensis Fisch. ex DC.
      (Zhi Gan Cao) root and the dried aqueous extract by LC-DAD.
AB  - A rapid, sensitive and specific reversed phase high-performance liquid
      chromatographic (LC) method with photodiode array detection (DAD) has been
      developed for the determination of glycyrrhizic acid in both the raw herb and a
      commercially prepared dried aqueous extract of Glycyrrhiza uralensis Fisch. ex
      DC. root (Zhi Gan Cao, liquorice). It was determined that extracting the raw herb
      in aqueous methanol (50:50 v/v) by sonication for 2 x 30 min was the most
      efficient sample preparation. Baseline resolution of the glycyrrhizic acid peak
      was achieved on a Varian Polaris RP C18-A (250 mm x 4.6 mm, 5 microm packing)
      column using an isocratic mobile phase consisting of 0. v aqueous phosphoric acid
      and acetonitrile in the ratio 60:40 v/v. Chromatograms were monitored between 200
      and 400 nm for peak purity assessments, with quantitation performed at 254 nm.
      Glycyrrhizic acid calibration curves in the concentration range of 14-558
      microg/ml were prepared on the day of analysis. Curve fitting was by the least
      squares method, with correlation coefficients of >0.9998 obtained each time. The
      average recovery at three spike levels (50, 100, 200%) was of 95.91+/-1.05% and
      98.36+/-3.45% (+/-S.D., n=7) for the spiked raw herb and dried aqueous extract
      respectively. The limit of detection and limit of quantitation was 0.52 and 1.72
      mg/g respectively for the raw herb, and 0.75 and 2.51 mg/g respectively for the
      dried aqueous extract. Identity confirmation of the chromatographic peak was
      achieved by (-) electrospray ionisation tandem mass spectrometry. The
      concentration of glycyrrhizic acid in the root and dried aqueous extract was
      found to be 31.1+/-0.2 and 40.4+/-0.3mg/g (+/-S.D., n=7) respectively.

PMID- 18325708
TI  - Capillary electrophoretic method for the simultaneous determination of
      tetracycline residues in fish samples.
AB  - A capillary electrophoresis (CE) method with UV detection was developed for
      simultaneous identification and quantitation of three tetracyclines: tetracycline
      (TC), oxytetracycline (OTC) and doxycycline (DC) in fish muscle samples. It was
      developed by analyzing a series of fish tissue samples containing TCs in
      different concentrations. The CE method was validated in terms of linearity,
      sensitivity, selectivity, decision limit (CCalpha), detection capability
      (CCbeta), precision and accuracy for investigated TCs. The limits of detection
      (LODs) estimated in the range 1.3-1.8 ng/g, while the limits of quantification
      (LOQs) for all analyzed TCs were ranged from 4.3 to 5.9 ng/g. The overall
      recoveries for TC, OTC and DC were 84.0, 80.6 and 89.2%, respectively, with
      repeatabilities below 6.2% R.S.D. In this report the use of extended light path
      (ELP) silica capillary and aqueous buffer solutions are combined with low
      wavelength UV detection (ca. 200 nm) to obtain the necessary sensitivity for
      simultaneous TCs determination in biological samples.

PMID- 18325709
TI  - Comparison of different culture media and growth conditions for recognition of
      Arcanobacterium haemolyticum.
AB  - Detection of Arcanobacterium haemolyticum is based upon typical beta-hemolysis
      and colony morphology, but it may go undetected if only conventional sheep blood
      agar media for detection of beta-hemolytic streptococci are used. The influence
      of different culture media, atmospheres, and times of incubation for the
      recognition of colonies of 47 isolates of A. haemolyticum was studied. After 48 h
      of incubation, trypticase soy agar with 5% horse blood in 5% CO(2) was the best
      medium.

PMID- 18325710
TI  - The role of CT perfusion imaging in acute stroke diagnosis: a large single-center
      experience.
AB  - The objective of this study was to determine the utility of computed tomography
      perfusion (CTP) scans in diagnosing acute ischemic stroke (AIS). CTP
      abnormalities in two contiguous supratentorial levels were correlated with
      diffusion weighted image (DWI) abnormalities on magnetic resonance imaging (the
      standard for stroke diagnosis) performed within 1 week in 422 suspected acute
      ischemic strokes. Of 157 AIS confirmed by DWI, 78 showed CTP abnormalities
      (sensitivity 49.7%). All of these examinations were performed with a mean of 35
      min from the initial emergency department neurological examination. Excluding
      small non-vascular territory strokes left 77 AIS with a total volume of infarcted
      tissue of more than 5 cc by DWI. Of these, 71 showed CTP abnormalities
      (sensitivity 92.2%). Of the 265 patients without AIS, none showed CTP
      abnormalities (specificity 100%). CTP is a rapid, readily available and effective
      method of diagnosing AIS in clinical practice, particularly the major
      intracranial vessel strokes that result in a more devastating outcome.

PMID- 18325711
TI  - Radiation cystitis: indication for hyperbaric oxygen.

PMID- 18325712
TI  - Contraindications to phenytoin in emergency department patients with seizures.
AB  - The objective of this study was to determine what contraindications to phenytoin
      exist in Emergency Department (ED) patients with a medical history of seizures.
      We conducted a retrospective chart review using ED medical records from 2005 at
      two network health care EDs. We identified potential patients through ICD-9
      (International Classification of Diseases, Ninth Revision) codes, selected only
      adult patients with a prior documented history of seizures, and reviewed these
      charts. From 201 charts reviewed, the three most common antiepileptic drugs taken
      by patients were: phenytoin (38%), levetiracetam (17%), and valproic acid (15%).
      For absolute contraindications to phenytoin, 4.5% of seizure patients had a known
      hypersensitivity to phenytoin and 1.5% were pregnant; however, no pregnant
      patients were taking phenytoin and only 1 person with hypersensitivity to
      phenytoin was taking phenytoin. For relative contraindications, 6% of seizure
      patients had liver disease, 8% had kidney disease, 9% had alcohol use/dependence,
      and 16% had diabetes. However, 55% of those with liver disease, 44% with kidney
      disease, 77% with alcohol use/dependence, and 53% with diabetes were currently
      taking phenytoin. Very few seizure patients in the ED have absolute
      contraindications to the use of phenytoin, and most with absolute
      contraindications are taking other antiepileptic drugs. Conversely, a greater
      proportion of seizure patients have relative contraindications and many are
      continuing to use phenytoin.

PMID- 18325713
TI  - Venous ultrasound testing for suspected thrombosis: incidence of significant non
      thrombotic findings.
AB  - Duplex ultrasound (US) is used to "rule out" deep venous thrombosis (DVT), but
      can also diagnose other causes of leg pain or swelling in Emergency Department
      (ED) patients. Recent literature suggests that US imaging is unnecessary among
      patients with low or moderate clinical probability of DVT with a normal D-dimer.
      We attempted to determine the incidence of clinically important incidental
      findings detected using venous US imaging in patients with suspected lower
      extremity DVT. We conducted a retrospective chart review of all ultrasounds
      performed by the non-invasive vascular laboratory on ED patients > 18 years old.
      Results were classified: normal, DVT, or incidental finding. The latter were
      classified as clinically significant major findings if the diagnosis led to
      immediate and specific treatment to prevent morbidity, or clinically significant
      minor findings. A total of 484 US studies were reviewed; 179 were excluded
      (arterial studies, penetrating trauma, upper extremity US). Findings among 305
      studies were: 238 (78%) normal, 28 (9%) DVT, and 39 (12%) incidental findings.
      Among 39 incidental findings, 10 were clinically significant major findings and
      29 clinically significant minor findings. Clinically significant major findings
      included: pseudoaneurysm, arterial occlusive disease, vascular graft
      complication, compartment syndrome, and tumor. Among 38 abnormal US studies that
      required immediate treatment, DVT comprised 74% (95% confidence interval 59%-85%)
      and important major incidental findings 26% (95% confidence interval 14%-41%).
      Among ED patients who underwent US to evaluate leg pain and swelling, 26% of
      positive studies showed clinically important findings other than DVT. Further
      research is needed to determine if D-dimer plus a clinical probability tool will
      include or exclude the patients with clinically significant major findings.

PMID- 18325714
TI  - Trimethoprim/sulfamethoxazole resistance in urinary tract infections.
AB  - Urinary tract infections (UTI) are among the most prevalent infectious diseases,
      and their financial burden on society is substantial. Management of UTIs has been
      complicated by the emergence of resistance to most commonly used antibiotics.
      Increasing prevalence of resistance has led to a gradual evolution in the
      antibiotics used to treat UTIs. The aims of this study were to determine the
      TMP/SMX (trimethoprim/sulfamethoxazole) resistance rate in patients with
      uncomplicated UTIs and to determine which empiric antibiotics are prescribed in
      the emergency department for the outpatient management of UTI. Between June 2004
      and May 2005, archives of the emergency department were searched retrospectively
      and the files of patients diagnosed with UTI were reviewed. Patients'
      demographical data, urine culture results, pathogen microorganisms, and TMP/SMX
      and fluoroquinolone (FQ) resistance rates were recorded. We obtained information
      from 274 files of patients who had been diagnosed with UTI. The most frequently
      isolated pathogen was Escherichia coli (54%). Of the 274 patients diagnosed with
      UTI, 251 had been started on empiric antibiotics. The most frequently prescribed
      antibiotics were FQs (85%), and the first choice in this group was ofloxacin
      (58%). The resistance rate for TMP/SMX was 34% and all of the resistant
      microorganisms were E. coli. The resistance rate for the FQ group was 16.4% and
      resistant microorganisms were E. coli. In the treatment of UTIs in our patient
      population, the most prescribed antibiotics were FQs. At the same time it was
      found that resistance rates against FQ antibiotics are as high as 16.4%.
      Unfortunately, in our population, in the near future, empiric FQ use may result
      in bacterial resistance.

PMID- 18325715
TI  - Antiplatelet therapy in acute coronary syndrome: not as confusing as you think.

PMID- 18325716
TI  - Community-associated CMRSA-10 (USA-300) is the predominant strain among
      methicillin-resistant Staphylococcus aureus strains causing skin and soft tissue
      infections in patients presenting to the emergency department of a Canadian
      tertiary care hospital.
AB  - Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an
      emerging pathogen first described among individuals with no contact with health
      care facilities. The purpose of this study was to determine the proportion of CA
      MRSA, defined by pulsed field gel electrophoresis (PFGE), in MRSA skin and soft
      tissue infections presenting to the Emergency Department (ED). We also aimed to
      describe the laboratory and clinical characteristics of CA-MRSA infections. From
      June 1, 2001 to May 30, 2005, MRSA isolates from skin and soft tissue infections
      presenting to the ED were reviewed. They were characterized by antibiotic
      susceptibilities and PFGE, and the presence of staphylococcal cassette chromosome
      (SCC) mec type IVa and Panton-Valentine leukocidin (PVL) genes was assessed on
      representative isolates. The medical records were reviewed to define risk
      factors. There were 95 isolates available for analysis, of which 58 (61%) were
      CMRSA-10 (USA-300), the predominant clone from 2003 onward. All representative
      isolates (24%) tested in this group had PVL genes and SCCmec type IVa. Their
      antibiogram showed 100% susceptibility to trimethoprim-sulfamethoxazole,
      rifampin, and fusidic acid, and 79% to clindamycin. Clinical comparison of CMRSA
      10 vs. hospital PFGE type strains showed 22% vs. 60%, respectively, for recent
      antibiotic use (p < 0.0001), 26% vs. 6%, respectively, for intravenous drug use
      (p < 0.05), and 57% vs. 6%, respectively, for soft tissue abscess (p < 0.001).
      CMRSA-10 is a major pathogen in skin and soft tissue abscesses in our ED. It has
      a characteristic susceptibility, and was associated with intravenous drug use,
      but not with recent antibiotic usage.

PMID- 18325717
TI  - Esophageal foreign body sensation: a rare presentation of angioedema.
AB  - Angioedema remains a rare but potentially life-threatening complication of
      angiotensin-converting enzyme (ACE) inhibitor use. Most presentations involve
      edema of the tongue or oral pharynx. However, in recent years, a visceral form
      involving the gastrointestinal tract also has been described. We present the case
      of a rare presentation of esophageal and retropharyngeal edema related to ACE
      inhibitor use. A review of ACE inhibitor-related angioedema is also presented.

PMID- 18325718
TI  - Oligomeric beta-amyloid(1-42) induces the expression of Alzheimer disease
      relevant proteins in cholinergic SN56.B5.G4 cells as revealed by proteomic
      analysis.
AB  - Alzheimer's disease (AD) is characterized by cholinergic dysfunction and
      progressive basal forebrain cell loss which has been hypothesized to be
      associated with extensive accumulation of beta-amyloid (Abeta). To reveal whether
      oligomeric Abeta displays a particular toxicity for cholinergic neurons, the
      cholinergic cell line SN56.B5.G4 (SN56) was used as a model. Recently performed
      microarray analyses demonstrated that genes affected by exposure of SN56 cells
      with 50 microM oligomeric Abeta(1-42) for 24 h were involved in protein
      modification and degradation [Heinitz, K., Beck, M., Schliebs, R., Perez-Polo,
      J.R., 2006. Toxicity mediated by soluble oligomers of beta-amyloid(1-42) on
      cholinergic SN56.B5.G4 cells. J. Neurochem. 98, 1930-1945]. Using a proteomic
      approach, we compared the levels of proteins and specially of phosphorylated
      proteins in cytosolic fractions of cell lysates from cholinergic SN56 cells
      exposed to 50 microM Abeta(1-42) for 24h to those in control incubations. We show
      here that the levels of calreticulin, and mitogen-activated protein kinase (MAPK)
      kinase 6c were up-regulated in cholinergic SN56 cells exposed to Abeta(1-42),
      while gamma-actin appeared down-regulated. Abeta(1-42) exposure of cholinergic
      SN56 cells led to decreased phosphorylation of phosphoproteins, such as the Rho
      GDP dissociation inhibitor, the ubiquitin carboxyl terminal hydrolase-1, and the
      tubulin alpha-chain isotype Malpha6, as compared to untreated control lysates.
      The proteins identified have also been reported to be affected in brains of AD
      patients, suggesting a potential role of Abeta in influencing the integrity and
      functioning of the proteome in AD.

PMID- 18325719
TI  - Perspectives of personal support workers and ventilator-users on training needs.
AB  - OBJECTIVES: Ventilator-users living in the community have significant personal
      care needs that are largely provided by paid personal support workers (PSWs). As
      part of a larger qualitative study exploring relationships between ventilator
      users and PSWs, this project explored training experiences and needs of PSWs from
      the perspectives of both groups. METHODS: Individual semi-structured interviews
      conducted with 10 PSWs and 10 ventilator-users living in Support Service Living
      Units in Ontario, Canada were tape recorded, transcribed verbatim and analyzed
      for emerging themes. RESULTS: Training experiences of PSWs varied significantly
      from on-the-job training, to a formal college diploma in personal care. While
      none received formal training in the specific care needs of ventilator-users such
      as tracheal suctioning, ventilator monitoring and tracheotomy care, all
      recommended improved training in this area. Their perspectives varied on whether
      training should be delivered in a formalized program or through individualized on
      the-job training. CONCLUSIONS: Despite differing perspectives on optimal training
      methods for PSWs, participants identified the need for initial and ongoing
      training to address specific needs of ventilator-users. PRACTICE IMPLICATION: We
      recommend the development of standardized PSW training modules adaptable for use
      in formal and on-site training programs that can accommodate a variety of
      learning styles and needs.

PMID- 18325720
TI  - Computerized dietary assessments compare well with interviewer administered diet
      histories for patients with type 2 diabetes mellitus in the primary healthcare
      setting.
AB  - OBJECTIVE: To test repeatability and relative validity of a computerized and
      interviewer administered assessment. METHODS: Using a context-based case-control
      trial, 41 adults with type 2 diabetes mellitus were randomized into four groups
      to complete dietary assessments (computerized or interviewer administered) at 0,
      2 and 8 weeks and food records at 0 and 2 weeks. Repeatability of reported
      energy, total fat, saturated, polyunsaturated and monounsaturated fatty acids
      between the computerized and interviewer administered methods were assessed using
      repeated measures ANOVA. Paired t-tests and Pearson's correlations determined
      relative validity of the assessments. RESULTS: Thirty-one patients completed all
      visits. Statistically significant differences were found between computerized and
      interviewer administered data for total fat (p=0.048) and saturated fatty acids
      (p=0.019) between 0 and 2 weeks. Computerized assessments correlated better with
      food records (r=0.16-0.52) compared with interviewer administered assessments (r=
      0.02 to 0.51). CONCLUSION: Computerized assessments saw a learning effect with
      repeated use indicating that users were becoming more familiar with the website
      with repeated use. Relative validity suggests that the website may capture more
      foods though this requires further investigation. PRACTICE IMPLICATIONS: By
      allowing patients to self-report their intakes on a computer, dietitians will
      have the ability to spend increased time with their patients counseling them
      toward change.

PMID- 18325721
TI  - Effects of recombinant bovine somatotropin (rbST) and season on plasma and milk
      insulin-like growth factors I (IGF-I) and II (IGF-II) in lactating dairy cows.
AB  - During two studies, effects of recombinant bovine somatotropin (rbST) on plasma
      and milk IGF's in cows adapted to summer (S; 12 cows) or winter (W; 12 cows)
      conditions were evaluated. Each study consisted of on-farm periods (30 days)
      followed by climatology chamber periods (CC; 30 days). Cows were given daily
      injections of rbST, Sometribove, USAN (25mg/day; 6 cows each study) or saline
      (control; 6 cows each study). During on-farm periods, blood and milk (am and pm)
      samples were collected once weekly. During CC periods, blood samples were
      collected every 2 days and milk samples (am and pm) were collected daily. Plasma
      IGF-I and IGF-II were increased in cows treated with rbST. A pronounced seasonal
      pattern in basal and rbST-stimulated plasma IGF-I but not IGF-II was detected.
      Higher basal and rbST-stimulated plasma IGF-I concentrations in S occurred
      despite large decreases in feed intake and energy balance. Milk IGF-I and IGF-II
      was not affected by rbST treatment or season. Although milk IGF-I and IGF-II
      concentrations were unaffected by rbST treatment, total IGF-output increased due
      to increased milk yield. The observed seasonal patterns in plasma IGF-I may be
      indicative of seasonal differences in the coupling of the somatotropin-IGF axis.
      In particular, we failed to detect an uncoupling of the somatotropin-IGF-I axis
      in S despite an induced negative energy balance during thermal stress.

PMID- 18325722
TI  - Patterns of gene expression in pig adipose tissue: insulin-like growth factor
      system proteins, neuropeptide Y (NPY), NPY receptors, neurotrophic factors and
      other secreted factors.
AB  - Although cDNA microarray studies have examined gene expression in human and
      rodent adipose tissue, only one microarray study of adipose tissue from growing
      pigs has been reported. Total RNA was collected at slaughter from outer
      subcutaneous adipose tissue (OSQ) and middle subcutaneous adipose tissue (MSQ)
      from gilts at 90, 150, and 210 d (n=5 age(-1)). Dye labeled cDNA probes were
      hybridized to custom porcine microarrays (70-mer oligonucleotides). Gene
      expression of insulin-like growth factor binding proteins (IGFBPs), hormones,
      growth factors, neuropeptide Y (NPY) receptors (NPYRs) and other receptors in OSQ
      and MSQ changed little with age in growing pigs. Distinct patterns of relative
      gene expression were evident within NPYR and IGFBP family members in adipose
      tissue from growing pigs. Relative gene expression levels of NPY2R, NPY4R and
      angiopoietin 2 (ANG-2) distinguished OSQ and MSQ depots in growing pigs. We
      demonstrated, for the first time, the expression of IGFBP-7, IGFBP-5, NPY1R,
      NPY2R, NPY, connective tissue growth factor (CTGF), brain-derived neurotrophic
      factor (BDNF) and ciliary neurotrophic factor (CNTF) genes in pig adipose tissue
      with microarray and RT-PCR assays. Furthermore, adipose tissue CTGF gene
      expression was upregulated while NPY and NPY2R gene expression were significantly
      down regulated by age. These studies demonstrate that expression of neuropeptides
      and neurotrophic factors in pig adipose tissue may be involved in regulation of
      leptin secretion. Many other regulatory factors were not influenced by age in
      growing pigs but may be influenced by location or depot.

PMID- 18325723
TI  - Outcome of R1 resection in patients undergoing pancreatico-duodenectomy for
      pancreatic cancer.
AB  - BACKGROUND: Pancreatico-duodenectomy (PD) is the only potentially curative
      treatment for pancreatic cancer, but most surgeons are reluctant to perform a
      palliative resection. The aim was to define the outcome for microscopically
      incomplete PD (R1). METHODS: Ninety-nine consecutive patients underwent
      laparotomy to perform PD. Sixty-seven patients were resected and 32 underwent
      palliative bypass (PSB) because of locally advanced disease. RESULTS: Of the 67
      PD, 27 were classified as R0 and 40 as R1. Median survival for R0, R1 and PSB
      were 24, 18 and 9 months, respectively. Survival in the PSB group was 34% at 1
      year and 0% at 2 years. 1-, 2- and 5-year survival in the R0 and R1 groups was
      79% and 70%, 48.3% and 39.1%, 21.5% and 9.9%, respectively. Compared to PSB, both
      other groups were less likely to die over follow-up (p=0.002). Survival was not
      significantly different between the R0 and R1 groups (p=0.21). Perioperative
      morbidity and mortality were similar in the PD and PSB groups (29.9% and 3.0% vs
      31.3 and 3.1%, respectively, p=1.00). CONCLUSIONS: Better survival in the
      resection group and similar perioperative risk would support the decision to
      perform PD even when there is the possibility of incomplete microscopic
      clearance.

PMID- 18325724
TI  - Prognosis of patients with intrahepatic recurrence after hepatic resection for
      hepatocellular carcinoma: a retrospective study.
AB  - AIMS: Hepatic resection is the most effective therapy for hepatocellular
      carcinoma (HCC); however, intrahepatic recurrence is common. Predictors of
      survival after intrahepatic recurrence have not been fully investigated. To
      clarify the prognosis and choice of treatment of intrahepatic recurrence after
      hepatic resection, we conducted a comparative retrospective analysis of 147
      patients with HCC who underwent hepatic resection. METHODS: We retrospectively
      examined the relations between clinicopathologic factors, including the number of
      recurrent intrahepatic tumors and long-term prognosis after recurrence in 147 HCC
      patients who underwent resection. We also examined long-term survival after
      recurrence based on treatment types and recurrence pattern. RESULTS: Patients
      with multiple tumors (n=83) showed less tumor differentiation, more frequent
      portal invasion, a higher alpha-fetoprotein level, and larger tumors than did
      patients with solitary tumor (n=64). In the solitary tumor group, local ablation
      therapy and repeat hepatic resection were performed in 25 and 10, respectively.
      In the multiple tumor group, 59 were treated by transarterial chemoembolization.
      Multivariate analysis showed intraoperative blood transfusion and multiple tumors
      to be independent risk factors for poor cancer-related survival after recurrence.
      By subset analysis based on treatment types and recurrence pattern, survival
      after recurrence was significantly better in patients treated by local ablation
      therapy than those treated by other therapies in both solitary and multiple tumor
      groups. CONCLUSIONS: For patients with solitary recurrence, a good prognosis is
      predicted. Local ablation therapy is a best candidate for treatment of solitary
      and multiple intrahepatic recurrences after hepatic resection.

PMID- 18325725
TI  - Phenotype and function of dendritic cells and T-lymphocyte polarization in the
      human colonic mucosa and adenocarcinoma.
AB  - AIM: To evaluate the status of activation of the intestinal dendritic cells (DCs)
      and T lymphocytes (T cells) from surgical specimens of human colon and
      adenocarcinoma, and the potential effect of administration of interleukin 2 (IL
      2). METHODS: Patients undergoing colectomy for cancer were randomized to receive
      subcutaneous IL-2 (12million UI/day) (treated group; n=10) for 3days before
      operation or no treatment (control group, n=10). DCs and T cells were isolated
      and purified from the lamina propria (LP) of segments of normal colon and
      adenocarcinoma of both groups. Cell phenotype was determined by expression of
      membrane receptors. Interaction between DC and T cells was assesses by a mixed
      leukocyte reaction using naive T cells co-cultured with DCs. CD4+ T-cell
      polarization was studied by intracellular staining with monoclonal antibodies for
      interleukin-4 and interferon-gamma. RESULTS: CD4+ T cells were significantly less
      in tumour than in LP (p<0.05) in both treated and control groups. IL-2 did not
      modify the number of any of the T-cell subsets analysed. In contrast, T cells
      isolated from LP and neoplasm of treated patients produced more interferon-gamma
      and less interleukin-4 (p<0.05 vs. controls). IL-2 administration significantly
      increased (p<0.05) the number of mature, myeloid and plasmocytoid DCs compared to
      controls. Allogeneic naive T cells were polarized toward a Th1 type of response
      which appeared to be mediated by IL-2 activated DCs. CONCLUSIONS: systemic IL-2
      treatment may have immunomodulatory properties on intestinal DC maturation and
      drive a Th1 mediated anti-neoplastic response.

PMID- 18325726
TI  - Epigallocatechin-3-gallate ameliorates rats colitis induced by acetic acid.
AB  - BACKGROUND: Epigallocatechin-3-gallate (EGCG) has been recently proved to possess
      anti-inflammatory effects. AIMS: To investigate the effect and mechanism of
      epigallocatechin-3-gallate (EGCG) treatment in rats with acetic acid-induced
      colitis. METHODS: Sixty male rats were randomly assigned into 4 groups: normal
      control (n=10), model placebo (n=20), EGCG (n=15), and SASP (n=15). The normal
      group was treated with regular feeding, while the other 3 groups were treated
      orally with saline 2ml/d, EGCG 50mg/kg/d, and SASP 0.25g/kg/d, respectively, for
      7 days using an established colitis model induced by 8% acetic acid. The disease
      activity index (DAI) and the therapeutic effects were evaluated. Colon mucosa
      damage index (CMDI) and histological score were determined. The activities of
      nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), tumor
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) and tissue
      expression of nuclear factor-kappaBp65 (NF-kappaBp65) were measured. RESULTS:
      EGCG notably improved the DAI (1.1+/-0.9), CMDI (1.5+/-0.9) and histological
      scores (4.6+/-3.1) compared with the placebo (3.9+/-0.4, p<0.01; 3.3+/-0.6,
      p<0.05; 9.3+/-2.8, p<0.01) and SASP groups (3.0+/-1.2, p<0.01; 2.3+/-0.9, p<0.05;
      7.9+/-4.0, p<0.05). Compared with the placebo and SASP groups, the levels of NO
      (9.1+/-5.6micromol/gprot), MDA (0.9+/-0.6nmol/gprot), TNF-alpha (24.4+/
      1.6PG/ml), IFN-gamma (33.3+/-0.9PG/ml), and NF-kappaBp65 (28.0+/-2.8cells/mm(3))
      in EGCG-treated group were significantly reduced (p<0.05 or p<0.01), while that
      of SOD (185.4+/-24.6U/mgprot) was increased remarkably (p<0.05). CONCLUSION: EGCG
      exerts its antioxidant activity via decreasing NO, MDA, and increasing SOD. It
      ameliorates mucosal inflammation by inhibiting the production of TNF-alpha, IFN
      gamma and NF-kappaBp65 and may be a potential therapeutic agent in colitis.

PMID- 18325727
TI  - Involvement of anti-inflammatory heme oxygenase-1 in the inhibitory effect of
      curcumin on the expression of pro-inflammatory inducible nitric oxide synthase in
      RAW264.7 macrophages.
AB  - Curcumin, at high concentrations (>2 microM), inhibits the production of nitric
      oxide (NO) and the expression of inducible NO synthase (iNOS) through
      inactivation of nuclear factor (NF)-kappaB and, at low concentrations, induces
      the expression of heme oxygenase (HO)-1 in macrophages. Here, we demonstrated
      that curcumin at low concentrations (0.5-2 microM) can also inhibit NO production
      and iNOS expression in lipopolysaccharide (LPS)-activated RAW264.7 macrophages
      only when the cells were pretreated for at least 6h with curcumin. Curcumin
      induced dose- and time-dependent HO-1 expression, and this was coincident with
      the inhibitory effects of low concentrations of curcumin on NO production and
      iNOS expression. Blockage of HO-1 activity or knockdown of HO-1 expression
      abolished the inhibitory effects of curcumin. Over-expression of HO-1 or
      exogenous addition of carbon monoxide, a byproduct derived from heme degradation,
      mimicked the inhibitory action of low concentrations of curcumin. Moreover, LPS
      induced NF-kappaB was diminished in macrophages subjected to prolonged treatment
      with low concentrations of curcumin. Treatment with HO inhibitor abolished the
      inhibitory effect of curcumin on LPS-induced NF-kappaB activation. Collectively,
      we provide evidence to support the important role of HO-1 in inhibition of NO
      production and iNOS expression by curcumin even at low concentrations.

PMID- 18325728
TI  - Effect of chronic ethanol exposure on the hepatotoxicity of ecstasy in mice: an
      ex vivo study.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA) is frequently consumed at "rave" parties
      by polydrug users that usually take this drug in association with ethanol. In
      addition, many young people are repeatedly exposed to ethanol, which likely leads
      to tolerance phenomena. Both compounds are metabolized in the liver, with
      formation of hepatotoxic metabolites, which gives high relevance to the
      evaluation of their putative toxicological interaction. Therefore, the aim of
      this study was to evaluate the toxicity induced by 0.8 and 1.6 mM MDMA to freshly
      isolated hepatocytes obtained from ethanol-treated mice whose tap drinking water
      was replaced by a 5% ethanol solution for 1 week and, afterwards, by a 12%
      ethanol solution for 8 weeks (ethanol group) comparatively to non-treated animals
      (non-ethanol group). The hepatocytes were incubated under normothermic and
      hyperthermic conditions in order to simulate in vitro the hyperthermic response
      induced in vivo by MDMA, a condition that has been recognized as a life
      threatening effect associated with MDMA exposure and implicated in its
      hepatotoxicity. Six mice treated under the same protocol as the ethanol group
      were used for histological analysis, and compared to non-ethanol-treated animals.
      The pre-treatment of mice with ethanol caused a significant decrease in the
      hepatocytes yield in the isolation procedure comparatively to the non-ethanol
      group, which can be explained by an increase in collagen deposition along the
      hepatic parenchyma as observed in the histological analysis. The initial cell
      viability of hepatocytes suspensions was similar between ethanol and non-ethanol
      groups. However, the ethanol group showed a higher GSH oxidation rate, which was
      enhanced under hyperthermia. Additionally, a concentration-dependent MDMA-induced
      loss of cell viability and ATP depletion was observed for both groups, at 41
      degrees C. In conclusion, the repeated treatment with ethanol seems to increase
      the vulnerability of freshly isolated mice hepatocytes towards pro-oxidant
      conditions, as ascertained by the increase in collagen deposition, lower
      hepatocyte yield and decreased glutathione levels. However, MDMA toxicity to the
      isolated hepatocytes was independent of ethanol pre-treatment, while
      significantly dependent on incubation temperature.

PMID- 18325729
TI  - Preclinical evidence for nitrogen-containing bisphosphonate inhibition of
      farnesyl diphosphate (FPP) synthase in the kidney: implications for renal safety.
AB  - Bisphosphonates are potent inhibitors of osteoclast-mediated bone resorption and
      play an important role in the treatment of osteoporosis, metastatic bone disease,
      and Paget disease. However, nephrotoxicity has been reported with some
      bisphosphonates. Nitrogen-containing bisphosphonates directly inhibit farnesyl
      diphosphate (FPP) synthase activity (mevalonate pathway) and reduce protein
      prenylation leading to osteoclast cell death. The aim here was to elucidate if
      this inhibition also occurs in kidney cells and may directly account for
      nephrotoxicity. In an exploratory study in rats receiving zoledronate or
      ibandronate an approximate 2-fold increase in FPP synthase mRNA levels was
      observed in the kidney. The involvement of the mevalonate pathway was confirmed
      in subsequent in vitro studies with zoledronate, ibandronate, and pamidronate,
      using the non-nitrogen containing bisphosphonate clodronate as a comparator. In
      vitro changes in FPP synthase mRNA expression, enzyme activity, and levels of
      prenylated proteins were assessed. Using two cell lines (a rat normal kidney cell
      line, NRK-52E, and a human kidney proximal tubule cell line, HK-2), ibandronate
      and zoledronate were identified as most cytotoxic (EC50: 23/>1000 microM and
      16/82 microM, respectively) and as the most potent inhibitors of FPP synthase
      (IC50; 1.6/7.4 microM and 0.5/0.7 microM, respectively). In both cell lines,
      inhibition of FPP synthase activity occurred prior to a decrease in levels of
      prenylated proteins followed by cytotoxicity. This further supports that the
      mechanism responsible for osteoclast inhibition (therapeutic effect) might also
      underlie the mechanism of nephrotoxicity.

PMID- 18325730
TI  - The effects of direct versus witnessed threat on emergency department healthcare
      workers: implications for PTSD criterion A.
AB  - We compared post-traumatic stress disorder (PTSD) symptom severity and symptom
      cluster profiles in hospital emergency department (ED) medical staff (N=100) who
      experienced an emotionally distressing work event that presented either a direct
      threat to themselves or a witnessed threat to patients. The two groups displayed
      similar levels of PTSD symptoms, however, they differed on symptom profiles and
      work consequences. The direct threat group experienced significantly greater fear
      during the event, more ongoing arousal symptoms, and more job dissatisfaction
      than the witnessed threat group. The witnessed threat group was more likely to
      appraise their PTSD symptoms as reflecting personal weakness. Overall, the
      results point to the need for further research to identify distinctive features
      of responses to different types of traumatic stressors.

PMID- 18325731
TI  - Clinical assessment of left ventricular systolic torsion: effects of myocardial
      infarction and ischemia.
AB  - BACKGROUND: The helical arrangement of myocardial fibers leads to left
      ventricular (LV) torsion, a vital contributor to systolic and diastolic function.
      Rotation and torsion can now be measured; we sought to determine the utility of
      torsion as a marker of LV function at rest and after stress in patients with
      myocardial infarctions (MIs) and ischemia. METHODS: Dobutamine echocardiography
      was performed in 125 patients. After the exclusion of 40 patients with suboptimal
      images, LV systolic rotation and torsion were measured offline using speckle
      tracking echocardiography in 44 patients with and 41 without prior MIs.
      Hemodynamic findings and the extent of infarction and ischemia were correlated
      with length-corrected torsion measurements at baseline and at peak-dose
      dobutamine. RESULTS: Resting global and regional LV systolic torsion were
      significantly reduced in patients with compared with those without previous MIs
      (1.16 +/- 1.15 degrees /cm vs 3.16 +/- 1.3 degrees /cm, P < .001), and global
      systolic torsion was an independent correlate of LV ejection fraction (LVEF) (P =
      .04). There was no difference in global LV systolic torsion in patients with
      anteroapical or inferoposterior infarcts (1.81 +/- 1.13 degrees /cm vs 2.27 +/-
      1.18 degrees /cm, P = NS) and no differences in regional torsion. Torsion was
      most impaired in patients with multiple areas of infarction (1.03 +/- 0.89
      degrees /cm, P < .001). However, dobutamine-induced ischemia (2.59 +/- 1.14
      ischemic segments) had no effect on global and regional systolic torsion at peak
      dose or change in torsion from rest to peak dose. CONCLUSIONS: The influence of
      MI on LV systolic torsion appears to be related to infarct size rather than site,
      and torsion was an independent determinant of resting function. LV torsion was
      not significantly influenced by stress-induced myocardial ischemia.

PMID- 18325732
TI  - Evaluation of left main coronary artery stenosis by transthoracic
      echocardiography.
AB  - OBJECTIVE: We sought to demonstrate left main coronary artery (LM) stenosis by
      transthoracic echocardiography. BACKGROUND: Evaluation of LM stenosis was done
      mostly by transesophageal echocardiography in patients with coronary artery
      disease. METHODS: A total of 1456 patients with coronary artery disease were
      studied, of which 801 patients (55%) had adequate coronary flow assessment. The
      LM and the adjacent segments of left anterior descending coronary artery and left
      circumflex coronary artery were evaluated by color flow and Doppler. Mosaic flow
      and/or peak diastolic velocity of greater than or equal to 1.5 m/s was considered
      abnormal. These findings were correlated with stenoses at coronary angiography. A
      total of 40 patients who had abnormal diastolic flow in LM by transthoracic
      echocardiography constituted group 1 and 56 patients with normal LM flow
      constituted the control group (group 2). RESULTS: The peak diastolic velocities
      in LM in group 1 ranged between 1.5 and 4.4 m/s (mean 2.11 +/- 0.78 m/s). Of the
      40 patients in group 1, 34 had significant LM stenosis by coronary angiography
      (sensitivity of 85%, positive predictive value 82.5%). The velocities in LM in
      group 2 ranged between 0.4 and 1.2 m/s (mean 0.66 +/- 0.25 m/s). In all, 49 of 56
      patients in this group had normal LM on coronary angiography (88% specificity,
      negative predictive value 90.7%). The remaining 7 had distal LM stenosis. Mosaic
      flow in LM indicated significant LM stenosis in 85% of patients, whereas normal
      flow in LM did not rule out distal LM stenosis in 12% of patients. CONCLUSIONS:
      LM stenosis could be assessed by transthoracic echocardiography with an
      acceptable degree of sensitivity and specificity.

PMID- 18325733
TI  - Diagnostic value of left ventricular outflow area in patients with hypertrophic
      cardiomyopathy: a real-time three-dimensional echocardiographic study.
AB  - BACKGROUND: Earlier studies demonstrated the ability of real-time 3-dimensional
      (3D) echocardiography (3DE) to measure left ventricular outflow tract (LVOT) area
      (A(LVOT)) in patients with hypertrophic cardiomyopathy (HCM). However, its
      clinical value is unknown. OBJECTIVE: We sought to investigate the feasibility
      and accuracy of real-time 3DE-derived A(LVOT) to diagnose significant LVOT
      obstruction in a large number of patients with HCM. METHODS: A total of 162
      patients with HCM had 3DE by using a volumetric system. The smallest A(LVOT)
      during systole was determined by moving a 2-dimensional plane in 3D space. The
      pressure gradient across LVOT was assessed by continuous wave Doppler method.
      Provocation was performed in patients without significant LVOT obstruction
      (pressure gradient across LVOT < 50 mm Hg) at rest. RESULTS: Twenty (12%)
      patients with poor image quality of 3DE were excluded; 16 (28%) patients with a
      volumetric system, but only 4 (4%) patients with commercial equipment (P < .001).
      In the remaining 142 patients, A(LVOT) inversely correlated with pressure
      gradient across LVOT both at rest (r = 0.82, P < .001) and after provocation (r =
      0.60, P < .001). The value of A(LVOT) less than 0.85 cm(2) and less than 2.0
      cm(2) predicted resting and provokable LVOT obstruction with sensitivity of 87%
      and 81%, and specificity of 77% and 90%, respectively. CONCLUSIONS: Real-time 3DE
      measurement of A(LVOT) was successful in diagnosing and quantifying LVOT
      obstruction at rest and after provocation in a large number of patients with HCM.

PMID- 18325734
TI  - Noninvasive differentiation of pulmonary arterial and venous hypertension using
      conventional and Doppler tissue imaging echocardiography.
AB  - To determine whether pulmonary arterial hypertension (PAH) and pulmonary venous
      hypertension (PVH) can be differentiated noninvasively, we reviewed data on 44
      patients with pulmonary artery systolic pressure greater than or equal to 40 mm
      Hg by echocardiography and cardiac catheterization performed within 7 days of
      each other. Based on left ventricular end-diastolic pressure or pulmonary
      capillary wedge pressure, 20 patients were classified as having PVH and 24 as
      having PAH. Early (E) and late (A) diastolic mitral inflow velocities,
      deceleration time, early diastolic mitral annular velocity (E'), and E/A and E/E'
      ratios were remeasured in the two groups. Compared with patients with PAH, those
      with PVH had significantly higher E (107.8 +/- 27.3 vs 65.0 +/- 24.0 cm/s, P <
      .001), E/A (2.4 +/- 1.0 vs 0.9 +/- 0.4, P < .001), and E/E' (14.3 +/- 4.3 vs 5.1
      +/- 1.9, P < .001), and significantly lower A (55.5 +/- 33.5 vs 74.1 +/- 20.8
      cm/s, P < .001), E' (8.0 +/- 2.5 vs 13.1 +/- 3.6 cm/s, P = .001), and
      deceleration time (148.5 +/- 49.0 vs 192.3 +/- 41.9 milliseconds, P = .003). The
      area under receiver operating characteristic curve was 97% for E/E' and 91% for
      E/A. Optimal cutoff for diagnosing PVH was 9.2 for E/E' (sensitivity 95%,
      specificity 96%) and 1.7 for E/A (sensitivity 75%, specificity 91%). PAH and PVH
      may be differentiated by readily obtainable conventional and tissue Doppler
      parameters.

PMID- 18325735
TI  - Doppler strain imaging closely reflects myocardial energetic status in acute
      progressive ischemia and indicates energetic recovery after reperfusion.
AB  - BACKGROUND: Capitalizing on mechanoenergetic coupling, we investigated whether
      strain echocardiography can noninvasively estimate the ratio of adenosine
      triphosphate (ATP) to adenosine diphosphate (ADP), a marker of energetic status
      during acute myocardial ischemia and reperfusion. METHODS: Twenty-eight pigs were
      divided into 7 groups (1 baseline, 4 ischemic, and 2 reperfusion). Ischemia was
      induced by left anterior descending coronary artery occlusion. Longitudinal
      systolic lengthening (SL) and postsystolic shortening (PSS) strain were measured
      by echocardiography. The ATP/ADP ratio was obtained from myocardial biopsies in
      the ischemic and control regions. RESULTS: SL and PSS strain and the ATP/ADP
      ratio progressively decreased (P < .05) with increased duration (12, 40, 120, and
      200 minutes) of ischemia. A mathematical formula (ATP/ADP = -0.97 + 0.25 x PSS
      strain + 0.20 x SL strain) estimated best the ATP/ADP ratio (r = 0.94, P < .05).
      Reperfusion after 12 but not after 120 minutes of ischemia significantly improved
      the ATP/ADP ratio and decreased SL and PSS strain. CONCLUSIONS: Strain
      echocardiography closely reflected changes and enabled the noninvasive estimation
      of the ATP/ADP ratio. A higher ATP/ADP ratio is associated with functional
      improvement after reperfusion.

PMID- 18325736
TI  - Longitudinal strain and torsion assessed by two-dimensional speckle tracking
      correlate with the serum level of tissue inhibitor of matrix metalloproteinase-1,
      a marker of myocardial fibrosis, in patients with hypertension.
AB  - BACKGROUND: We hypothesized that the alterations of myocardial collagen turnover
      in patients with hypertension may be involved in the early changes of regional
      contractile function assessed by a new speckle tracking method. METHODS: In 56
      patients with untreated hypertension (48 +/- 11 years, ejection fraction > 55%)
      and 20 age-matched control subjects, the serum levels of aminoterminal propeptide
      of procollagen I/III and tissue inhibitor of matrix metalloproteinase (TIMP)-1
      were measured by radioimmunoassay and enzyme immunoassay. To assess the regional
      contractile function, the average of negative longitudinal strain of 6 segments
      at apical 4-chamber view (longitudinal epsilon), the average of radial strain
      (radial epsilon) and the average of circumferential strain (circumferential
      epsilon) of 6 mid-left ventricular (LV) segments, and basal-to-apical torsion
      were obtained by 2-dimensional speckle tracking imaging. RESULTS: Compared with
      control group, longitudinal epsilon was significantly decreased (-20.4 +/- 3.0%
      vs -22.1 +/- 2.2%, P = .030) and basal-to-apical torsion was increased (20.5 +/-
      5.7 degrees vs 17.4 +/- 3.7 degrees, P = .013) in patient group. The serum level
      of log TIMP-1 was higher in the patients (3.6 +/- 0.6 vs 3.0 +/- 0.5, P < .001).
      The serum log TIMP-1 significantly correlated with longitudinal epsilon (r =
      0.405, P = .015), basal-to-apical torsion (r = 0.331, P = .017), and the LV mass
      (r = 0.266, P = .047). In multivariate analysis, longitudinal epsilon (beta =
      0.326, P = .015) and basal-to-apical torsion (beta = 0.402, P = .003)
      independently correlated with the serum TIMP-1 level. CONCLUSION: In patients who
      are hypertensive with normal ejection fraction, impaired longitudinal epsilon and
      increased LV torsion correlated with serum TIMP-1, which suggests that the change
      in collagen turnover and the myocardial fibrotic process may affect the early
      contractile dysfunction of LV.

PMID- 18325737
TI  - The impact of exercise-induced changes in intraventricular dyssynchrony on
      functional improvement in patients with nonischemic cardiomyopathy.
AB  - BACKGROUND: The assessment of dynamic intraventricular dyssynchrony has been
      reported to be feasible in a clinical setting. However, its prognostic
      implication in functional improvement has not yet been investigated. METHODS:
      Symptom-limited, supine bicycle exercise was performed on 41 patients with
      nonischemic cardiomyopathy (52 +/- 12 years, ejection fraction < 40%). Using
      Doppler tissue imaging, the average of peak systolic velocities at 6 basal
      segments was obtained at rest and peak exercise. Dyssynchrony index (Ts-SD12) was
      defined as the SD of the time to peak systolic velocities at 12 left ventricular
      segments. The percent change of end-systolic volume (%Delta ESV) was calculated
      at follow-up. A 15% or greater reduction in end-systolic volume (%Delta ESV < 
      15%) was considered as functional improvement. RESULTS: During exercise, changes
      in dyssynchrony (Delta Ts-SD12) were individually variable. Average of peak
      systolic velocities (V) at 6 basal segments at peak exercise independently
      correlated with Ts-SD12 at peak exercise (beta = -0.541, P < .001). Follow-up
      echocardiography was performed on 35 patients after medical treatment for 13.0 +/
      4.9 months. There was significant association of %Delta ESV with the change in
      mitral regurgitation (r = 0.434, P = .009), disease duration (r = 0.343, P =
      .045), QRS interval (r = 0.347, P = .041), and Delta Ts-SD12 (r = 0.511, P =
      .002). Multivariate analysis identified Ts-SD12 measured at peak exercise as the
      strongest predictor for functional improvement (%Delta ESV: beta = 0.577, P <
      .001; and Delta ejection fraction: beta = -0.563, P < .001). CONCLUSION: In
      patients with heart failure, dynamic dyssynchrony can be assessed during
      exercise. Ts-SD12 at peak exercise may be an independent predictor for reverse
      remodeling with medical treatment.

PMID- 18325738
TI  - System-level investigation into the regulatory mechanism of the calcineurin/NFAT
      signaling pathway.
AB  - Calcineurn/nuclear factor of the activated T cell (CaN/NFAT) signaling pathway
      plays crucial roles in the development of cardiac hypertrophy, Down's syndrome,
      and autoimmune diseases in response to pathological stimuli. The aim of the
      present study is to get a system-level understanding on the regulatory mechanism
      of CaN/NFAT signaling pathway in consideration of the controversial roles of
      myocyte-enriched calcineurin interacting protein1 (MCIP1) for varying stress
      stimuli. To this end, we have developed an experimentally validated mathematical
      model and carried out computer simulations as well as cell-based experiments.
      Quantitative overexpression and knock-down experiments in C2C12 myoblasts have
      revealed that MCIP1 functions only as a calcineurin inhibitor. We have also
      observed a biphasic response of the NFAT activity with increasing stimuli of
      isoproterenol. Through extensive in silico simulations, we have discovered that
      the NFAT activity is primarily modulated by ERK5 and MCIP1 under mild
      isoproterenol stimuli whereas it is mainly modulated by atrogin1 (muscle atrophy
      F-box protein) under strong isoproterenol stimuli. This study shows that a system
      level analysis may help understanding CaN/NFAT signaling-associated disease.

PMID- 18325739
TI  - Orthotopic bone formation in titanium fiber mesh loaded with platelet-rich plasma
      and placed in segmental defects.
AB  - The effect of platelet-rich plasma (PRP) on bone formation was investigated in a
      rabbit segmental radial defect model. The purpose of the study was to evaluate
      the bone inductive properties of PRP with titanium fiber mesh and autologous bone
      chips in a 15-mm rabbit radial defect model. Eighteen New Zealand white rabbits
      were divided into three groups: I, PRP with autologous bone (PRP-Ti-Bone); II,
      autologous bone (Ti-Bone); III, control group (Ti). The implants were placed in
      the radial defect for 12 weeks. After sacrifice, all specimens were harvested for
      histological, histomorphometrical and radiographic analysis. Histomorphometrical
      analysis showed that bone formation was higher in the implants with PRP (PRP-Ti
      Bone: 37+/-8%) than in those without PRP (Ti-bone: 25+/-6% and Ti: 25+/-5%) after
      12 weeks of implantation. It was concluded that PRP has a stimulatory effect on
      bone formation in titanium fiber mesh filled with autologous bone graft in
      segmental bone defects. Titanium fiber mesh was also shown to be an excellent
      scaffold material for the application of autologous bone grafts with or without
      PRP.

PMID- 18325740
TI  - High-dose galantamine augmentation inferior to placebo on attention, inhibitory
      control and working memory performance in nonsmokers with schizophrenia.
AB  - Dysfunction in the neuronal nicotinic acetylcholine receptor (nAChR) system has
      been implicated in the pathophysiology of schizophrenia, and it has been
      postulated that treatments that increase nAChR activity may improve symptoms of
      the disorder. We investigated the effects of the acetylcholinesterase inhibitor
      and allosteric nAChR modulator, galantamine, on cognitive performance and
      clinical symptoms when added to a stable antipsychotic medication regimen in
      nonsmoking outpatients with schizophrenia in a double-blind, placebo-controlled,
      parallel-group design. Participants were randomized to receive either galantamine
      (n=10) up to 32 mg/day or identical placebo (n=10) for 8 weeks and completed a
      cognitive battery at baseline and week 8 and clinical scales at baseline, week 4
      and week 8. The primary outcome measure was attentional performance as measured
      by the d' measure in the Continuous Performance Test - Identical Pairs (CPT-IP)
      Version. Contrary to our hypothesis, galantamine treatment was associated with
      inferior performance on the CPT-IP, on the three-card Stroop task, and on the
      Letter-Number Span task without reordering. Galantamine had no effect on clinical
      symptoms. In summary, galantamine treatment, at a dose of 32 mg/day, was well
      tolerated but was not effective as an adjunctive treatment for cognitive deficits
      in stable nonsmokers with schizophrenia.

PMID- 18325741
TI  - Anti-apoptotic role of S100A8 in X-ray irradiated keratinocytes.
AB  - BACKGROUND: Ionizing radiation is used to treat a lot of cancers, however, it
      also produced unwanted side effect on normal tissues, such as radiodermatitis. We
      previously established an animal model for radiodermatitis, and identified many
      of radiation-induced genes by cDNA microarray. Of the candidates, we chose S100A8
      gene for a further study. OBJECTIVE: The aim of this study is to investigate the
      functional role of S100A8 in X-ray irradiated keratinocytes. METHODS: RT-PCR and
      immunohistochemistry were performed to demonstrate the S100A8 induction by X-ray
      irradiation. HaCaT keratinocytes were transduced with the recombinant adenovirus
      expressing GFP-S100A8, and then effects on cell cycle and apoptosis were analyzed
      using flow cytometry and Western blot. RESULTS: X-ray irradiation markedly
      induced S100A8 expression in the hyperplastic epidermis of mouse. Overexpression
      of S100A8 by adenoviral transduction led to the enhancement of cell proliferation
      in the absence and/or presence of X-ray irradiation, as compared with Ad/GFP
      control group. Furthermore, overexpression of S100A8 significantly protected the
      X-ray-induced apoptosis. CONCLUSION: These results suggest that S100A8 have an
      anti-apoptotic role in X-ray irradiated keratinocytes.

PMID- 18325742
TI  - Cortisol response to interpersonal stress in young adults with borderline
      personality disorder: a pilot study.
AB  - Hypothalamic-pituitary-adrenal axis dysregulation after stress was found to be
      associated with borderline personality disorder (BPD). Nine female BPD young
      adults and 12 control subjects were investigated for stress reactivity and
      recovery after an interpersonal conflict discussion with their mothers. BPD
      subjects showed a delayed cortisol response after psychosocial stress.

PMID- 18325743
TI  - Structural and biological behaviors of some nonionic Schiff-base amphiphiles and
      their Cu(II) and Fe(III) metal complexes.
AB  - Novel series of nonionic Schiff bases was synthesized and characterized using
      microelemental analysis, FTIR and (1)H NMR spectra. These Schiff bases and their
      complexes with Cu and Fe have been evaluated for their antibacterial activity
      against bacterial species such as Staphylococcus aureus, Pseudomonas aureus,
      Candida albi, Bacillus subtilis and Escherichia coli and their fungicidal
      activity against Aspcrgillus niger and Aspcrgillus flavus. The results of the
      biocidal activities showed high potent action of the synthesized Schiff bases
      towards both bacteria and fungi. Furthermore, complexation of these Schiff bases
      by Cu(II) and Fe(III) show the metal complexes to be more antibacterial and
      antifungal than the Schiff bases. The results were correlated to the surface
      activity and the transition metal type. The mode of action of these complexes was
      discussed.

PMID- 18325744
TI  - Preparation and characterization of Pluronic/TPGS mixed micelles for
      solubilization of camptothecin.
AB  - To increase the solubility and cytotoxicity of poorly soluble anticancer drug
      camptothecin (CPT), mixed micelles made of Pluronic P105 (P105) and d-alpha
      tocopheryl polyethylene glycol 1,000 succinate (TPGS) were prepared. The
      interaction of Pluronic and TPGS was studied and critical micelle concentration
      (CMC) was used to evaluate the micellar stability towards dilution. Poorly
      soluble anticancer drug CPT was incorporated into the mixed micelles. The
      solubility of CPT by the mixed micelles was more than that of the free drug. The
      cytotoxicity of the CPT-loaded mixed micelles against MCF-7 cancer cell in vitro
      was remarkably higher than that of the free drug.

PMID- 18325745
TI  - [Fibrodysplasia ossificans progressiva: orthopedic pitfalls and controversies].
AB  - Fibrodysplasia ossificans progressiva (FOP) is a rare disorder of the connective
      tissue associating malformation of the great toes and progressive heterotopic
      ossifications. Diagnosis is mostly clinical and currently no treatment is
      available. We report on the case of an 8 year old boy having an unusual form of
      FOP. We discuss clinical aspects of the disease and insist on the importance of
      early diagnosis, avoiding harmful events and therapeutic pitfalls.

PMID- 18325746
TI  - [Retroauricular dermatofibroma in a child simulating a malignant tumour].
AB  - BACKGROUND: Dermatofibroma represents one of the commonest benign soft tissue
      tumours, and its diagnosis is usually straightforward if classical
      clinicopathologic features are evident. It occurs frequently on the extremities
      and trunk, often in young adults during the 3(rd) and 4(th) decades. We report a
      peculiar case of an aggressive cellular dermatofibroma in a child that simulated
      a malignant tumour. Our aim is to discuss the differential diagnosis. CASE
      REPORT: An 8-year-old boy presented with a retroauricular tumour. Clinically, the
      lesion, 2 cm in diameter, was located in the left retroauricular region. It was
      nodular, erythematous, infiltrating the underlying tissue with an anterior spread
      leading to an amputation of the auricular lobule and a retraction of the tragus.
      Computerized axial tomography revealed a local tissular thickening extending in
      soft tissues without any bone involvement. A malignant lesion was initially
      suspected. A biopsy was performed. It was followed by a surgical resection. The
      lesion had the full microscopic characteristics of a cellular dermatofibroma.
      CONCLUSION: Dermatofibroma is one of the major differential diagnosis of nodular
      cutaneous tumours in children that simulate malignancy. Histologic examination
      with immunohistochemical study is essential for diagnosis.

PMID- 18325747
TI  - [Survey of the interest in giving parents an information brochure on
      bronchiolitis at the discharge from maternity ward].

PMID- 18325748
TI  - [Difficulties to follow up exposed to antiretroviral therapy and non infected
      children born from HIV-infected mother after 2 years of age].

PMID- 18325749
TI  - [The e-ethical advice in neonatology].

PMID- 18325750
TI  - [Recommendations for the management of bone demineralization in cystic fibrosis].
AB  - A high prevalence of low bone mineralization is documented in adult patients with
      cystic fibrosis (CF). Osteopenia is present in as much as 85% of adult patients
      and osteoporosis in 13 to 57% of them. In children, studies are discordant
      probably because of different control database. Denutrition, inflammation,
      vitamin D and vitamin K deficiency, altered sex hormone production,
      glucocorticoid therapy, and physical inactivity are well known risk factors for
      poor bone health. Puberty is a critical period and requires a careful follow-up
      for an optimal bone peak mass. This review is a consensus statement established
      by the national working group of the French Federation of CF Centers to develop
      practice guidelines for optimizing bone health in patients with CF.
      Recommendations for screening and for calcium, vitamin D and K supplementation
      are given. Further work is needed to define indications for treatment with
      biphosphonates and anabolic agents.

PMID- 18325751
TI  - [Odontogenic keratocyst related to a Gorlin syndrome: a case report].
AB  - We are reporting here, the case of a 9 years old boy with Gorlin syndrome
      diagnosis. Current knowledge on this syndrome is reviewed.

PMID- 18325752
TI  - Oxygen-enriched air for co-incineration of organic sludges with municipal solid
      waste: a pilot plant experiment.
AB  - Pilot-plant experiments were performed to evaluate the effect of oxygen
      enrichment on the co-incineration of MSW and organic sludge from a wastewater
      treatment facility. Combustion chamber temperatures, stack gas concentrations,
      i.e., CO(2) and CO, and the residual oxygen were measured. The maximum ratio of
      organic sludge waste to total waste input was 30 wt.%. Oxygen-enriched air, 22
      vol.% (dry basis) oxygen, was used for stable combustion. As the co-incineration
      ratio of the sludge increased, the primary and secondary combustion chamber
      temperatures were decreased to 900 and 750 degrees C, respectively, approximately
      100 degrees C below the proper incineration. However, if the supplied air was
      enriched with 22 vol.% (dry basis) oxygen content, the incinerator temperature
      was high enough to burn the waste mixture containing 30 wt.% moisture sludge,
      with an estimated heating value of 6.72 MJ/kg. There are two main benefits of
      using oxygen enrichment in the co-incineration. First, the sensible heat can be
      reduced as the quantity of nitrogen in the flue gas will be decreased. Second,
      the unburned carbon formation is reduced due to the oxygen-enriched burning of
      the waste, despite an increase in the sludge co-incineration ratio.

PMID- 18325753
TI  - Combustion characteristics of simulated gas fuel in a 30 kg/h scale pyrolysis
      melting incinerator.
AB  - Combustion characteristics of gas fuel in a pyrolysis-melting incinerator having
      a 30 kg/h capacity were investigated. Pyrolyzed gas from waste was simulated by
      propane that was injected in the combustion chamber, and burnt through multi
      staged combustion by distributing the combustion air to primary, secondary, and
      tertiary air nozzles. Temperatures and the concentrations of gas components in
      the combustion chamber were measured. Combustion performance was evaluated with
      respect to the temperature distribution and combustion gas concentrations of O2,
      CO and NOx. Using secondary air and/or tertiary air, the combustion performance
      was improved, and, in particular, NOx concentration decreased significantly
      following the tertiary air injection.

PMID- 18325754
TI  - Acquired resistance to tyrosine kinase inhibitors during cancer therapy.
AB  - Selective tyrosine kinase inhibitors have emerged as important therapeutic agents
      in the treatment of a variety of human malignancies. Although several of these
      inhibitors have marked clinical activity, it is widely recognized that the
      overall value of these agents is substantially limited by the acquisition of drug
      resistance, which eventually arises in most, if not all treated patients.
      Mechanisms of drug resistance are beginning to be elucidated through the
      molecular analysis of clinical specimens as well as through cell culture
      modeling. By identifying resistance mechanisms, it should be possible to develop
      'second-generation' inhibitors as well as rational drug combinations that can
      overcome or even prevent acquired resistance to kinase inhibitors, thereby
      enhancing clinical benefit.

PMID- 18325755
TI  - Pathways connecting inflammation and cancer.
AB  - Chronic and persistent inflammation contributes to cancer development and can
      predispose to carcinogenesis. Infection-driven inflammations are involved in the
      pathogenesis of approximately 15-20% of human tumors. However, even tumors that
      are not epidemiologically linked to pathogens are characterized by the presence
      of an inflammatory component in their microenvironment. Hallmarks of cancer
      associated inflammation include the presence of infiltrating leukocytes,
      cytokines, chemokines, growth factors, lipid messengers, and matrix-degrading
      enzymes. Schematically, two interrelated pathways link inflammation and cancer:
      (1) genetic events leading to neoplastic transformation promote the construction
      of an inflammatory milieu; (2) tumor-infiltrating leukocytes, in particular
      macrophages, are prime regulators of cancer inflammation. Thus, an intrinsic
      pathway of inflammation (driven in tumor cells), as well as an extrinsic pathway
      (in tumor-infiltrating leukocytes) have been described and both contribute to
      tumor progression.

PMID- 18325756
TI  - Improving cancer control in the European Union: conclusions from the Lisbon round
      table under the Portuguese EU Presidency, 2007.
AB  - Cancer is a major cause of morbidity and mortality in the European Union (EU),
      and a public health burden. Improving cancer control in the EU will require
      implementation of efficient strategies within Member States and better policy
      coordination between them. In cooperation between the rotating EU Presidencies of
      Germany (2007), Portugal (2007) and Slovenia (2008), special attention was
      devoted to an integrated approach to cancer control in EU policies and
      programmes. A round-table focussed on national cancer plans, population-based
      cancer registries and cancer screening programmes was held during the Health
      Strategies in Europe meeting in Lisbon in July 2007, under the Portuguese
      Presidency. These three topics were selected as critical for improving cancer
      control at both national and European levels. The round-table was designed to
      produce a set of recommendations to inform EU cancer policy. This paper provides
      a resume of the conclusions and recommendations, to stimulate wider discussion
      and policy development. The conclusions of the meeting were presented at the
      Employment, Social Policy, Health and Consumer Affairs Council in December 2007
      and cancer was included in the Council Conclusions for the new European Health
      Strategy. Success in cancer control will require consistent attention from future
      EU Presidencies, such as the initiative of the Slovenian EU Presidency in early
      2008.

PMID- 18325757
TI  - Efficacy and safety of a new testosterone-in-adhesive matrix patch applied every
      2 days for 1 year to hypogonadal men.
AB  - OBJECTIVES: To study long-term efficacy and safety of a testosterone-in-adhesive
      matrix patch, delivering 4.8 mg of testosterone daily. METHODS: Randomized, open
      label, multicenter 1-year study. 224 hypogonadal patients were included. 188
      received 2 patches of 60 cm2 every 48 h and 36 patients had IM testosterone
      enanthate injection every 3 weeks. T, bioavailable T (BT), DHT, E2, LH, FSH and
      SHBG and clinical symptom scores (AMS and MSF-4) were assessed at 3, 6 and 12
      months. RESULTS: In the patch group, T serum levels were above 3 ng/mL in 85% of
      patients and remained stable over time. BT, DHT and E2 levels were restored
      within physiological range. BT/T ratio varied from 20 to 70%. In the IM group,
      the percentages of "normalized" patients appeared to be lower, although the two
      groups cannot be adequately compared due to the kinetic profile of T following IM
      administration, resulting in greater variations of serum T levels, blood
      samplings occurring randomly at time of peak, trough, or in between. A
      significant correlation was found between T, BT and the MSF-4 changes. BT levels
      were significantly related to total AMS score. PSA values showed a mean (S.D.)
      increase of 0.13 (0.38), 0.23 (0.79) and 0.30 (1.47)ng/mL at weeks 14, 27 and 53,
      respectively. The patch was well tolerated with no negative impact either on
      lipid profile, or red blood cells. Administration site reactions occurred in 35
      patients (18.8%). Adhesiveness was good (>or=75%) in >90% patients over the 1
      year application period. CONCLUSION: Two 60 cm2 patches, allowed constant
      physiological levels of sexual hormones over time. This new patch was well
      tolerated, easy to use, well accepted by the patients and displayed a very good
      adhesiveness. Clinical efficacy was more related to BT than to T.

PMID- 18325758
TI  - Pharmacokinetic study of a new testosterone-in-adhesive matrix patch applied
      every 2 days to hypogonadal men.
AB  - The present study assessed pharmacokinetic testosterone time profile and dose
      proportionality after application of a new matrix testosterone patch (30, 45, and
      60 cm2 containing 0.5mg of testosterone per cm2). This open study was a single
      dose, three-period, crossover trial with a randomised treatment sequence in 24
      hypogonadal men, consisting in a single 48-h application of two patches of 2x 30
      cm2, 2x 45 cm2, 2x 60 cm2, separated by a 5-day wash-out. Testosterone
      concentrations were determined during patch application and after patch removal.
      Dose proportionality was assessed on baseline corrected, dose normalised
      parameters for C av,corr/D, C max,corr/D and AUC(0-48),corr/D. Testosterone
      concentrations rose during the first 9h following patch application, remained
      relatively sustained until 48 h and then decreased abruptly after patch removal,
      with a half-life of 1.3h. Testosterone levels were maintained above 3 ng/mL for
      42-45 h with all patches. C av were 3.39, 4.03 and 4.58 ng/mL and Cmax were 4.33,
      5.29 and 6.18 ng/mL according to the doses. AUC 0-48), C av and Cmax were dose
      dependent with mean ratios within the acceptance range (0.70-1.43). In
      conclusion, dose linearity was demonstrated between the different strengths of
      testosterone patches. Application resulted in dose proportional increases in
      serum T levels in hypogonadal men into the low to mid-normal range within the
      first hours and achieved steady state for 48 h. During this short term study with
      three consecutive patch applications, this patch was shown to be efficient,
      convenient and safe with excellent adhesiveness and skin tolerability, and with
      no cross-contamination to partner or to environment.

PMID- 18325759
TI  - Selection of Leptospirillum ferrooxidans SRPCBL and development for enhanced
      ferric regeneration in stirred tank and airlift column reactor.
AB  - Presence of Leptospirillum ferrooxidans plays significant role in ferric sulphate
      generation during bioleaching process. Thus, an attempt was made to select L.
      ferrooxidans from the polymetallic concentrate leachate and further developed it
      for enhanced ferric iron regeneration from the leachate in shake flask, stirred
      tank and column reactor. When ferric to ferrous iron ratio in the shake flask
      reached to 20:1, L. ferrooxidans out competed Acidithiobacillus ferrooxidans and
      accounted for more than 99% of the total population. The isolate was confirmed by
      16S rRNA genes sequence analysis and named as L. ferrooxidans SRPCBL. When the
      culture was exposure to UV dose and the oxidation-reduction potential of the
      inoculation medium was adjusted to 40 0mV by ferrous:ferric iron ratio, the IOR
      reached to as high as 1.2 g/L/h in shake flask, even with initial ferrous iron
      concentration of 200 g/L. The chalcopyrite concentrate leachate containing 12.8,
      15.7, and 42.0 g/L ferrous iron, ferric iron and copper, respectively was studied
      for ferric iron regeneration with the developed polymetallic resistant L.
      ferrooxidans SRPCBL in stirred tank and a developed biofilm airlift column, the
      highest IOR achieved were 2.20 g/L/h and 3.1 g/L/h, respectively, with ferrous
      oxidation efficiency of 98%. The ferric regeneration ability of the developed
      isolate from the leachate proves useful for a two-stage metal extraction process.

PMID- 18325760
TI  - Optimization of chemically defined medium for recombinant Pichia pastoris for
      biomass production.
AB  - A chemically defined medium was optimized for the maximum biomass production of
      recombinant Pichia pastoris in the fermentor cultures using glycerol as the sole
      carbon source. Optimization was done using the statistical methods for getting
      the optimal level of salts, trace metals and vitamins for the growth of
      recombinant P. pastoris. The response surface methodology was effective in
      optimizing nutritional requirements using the limited number of experiments. The
      optimum medium composition was found to be 20 g/L glycerol, 7.5 g/L (NH4)2SO4, 1
      g/L MgSO4.7H2O, 8.5 g/L KH2PO4, 1.5 mL/L vitamin solution and 20 mL/L trace metal
      solution. Using the optimized medium 11.25 g DCW/L biomass was produced giving a
      yield coefficient of 0.55 g biomass/g of glycerol in a batch culture. Chemostat
      cultivation of recombinant P. pastoris was done in the optimized medium at
      different dilution rates to determine the kinetic parameters for growth on
      glycerol. Maximum specific growth rate of 0.23 h(-1) and Monod saturation
      constant of 0.178 g/L were determined by applying Monod model on the steady state
      data. Products of fermentation pathway, ethanol and acetate, were not detected by
      HPLC even at higher dilution rates. This supports the notion that P. pastoris
      cells grow on glycerol by a respiratory route and are therefore an efficient
      biomass and protein producers.

PMID- 18325761
TI  - Comparison of biosorption properties of different kinds of fungi for the removal
      of Gryfalan Black RL metal-complex dye.
AB  - Three kinds of filamentous fungi (Rhizopus arrhizus, Trametes versicolor,
      Aspergillus niger) were tested for their ability to adsorb Gryfalan Black RL
      metal-complex dye as a function of pH, temperature and dye concentration. R.
      arrhizus and T. versicolor exhibited the maximum dye uptake at pH 2.0 and at 25
      degrees C while A. niger performed the highest dye biosorption at pH 1.0 and at
      35 degrees C. Sorption capacity of each biosorbent increased with increasing
      initial dye concentration. Among the three fungi, R. arrhizus was the most
      effective biosorbent showing a maximum dye uptake of 666.7 mg g(-1). The Langmuir
      model described the equilibrium data of each dye-fungus system accurately in the
      concentration and temperature ranges studied. Kinetic analysis indicated that
      both adsorption kinetics and internal diffusion played an important role on
      controlling the overall adsorption rate for each fungus. Thermodynamic analysis
      verified that A. niger biosorption was endothermic while the others were
      exothermic.

PMID- 18325762
TI  - Mass balance of nitrogen, and estimates of COD, nitrogen and phosphorus used in
      microbial synthesis as a function of sludge retention time in a sequencing batch
      reactor system.
AB  - This study investigated characteristics of a sequencing batch reactor (SBR)
      system which was varied with respect to sludge retention time (SRT) (5.9, 8.2,
      10.5, 12.2, and 16.2 days). The removal efficiencies of chemical oxygen demand
      (COD) were more than 90% under all SRT conditions, and the greatest efficiency
      (92.2%) occurred with a SRT of 16.2 days. As the SRT increased, the
      denitrification rate per mixed liquor suspended solids (MLSS) during the
      anoxic(I) period decreased significantly from 166.3 mg NO(X)(-)-N/g MLSS d to
      68.8 mg NO(X)(-)-N/g MLSS d. As the SRT increased, the phosphorus removal
      efficiency decreased from 47.1% (SRT of 5.9 days) to 31.0% for a SRT of 16.2
      days, because active phosphate release and uptake occurred under shorter SRT
      conditions. The mass balance of nitrogen (with respect to nitrogen in the
      influent) at a SRT of 16.2 days (the highest nitrogen removal efficiency) showed
      14.9% of nitrogen was removed in clarified water effluent, 49.7% was removed by
      the sludge waste process and 33.3% was removed by denitrification. Nitrogen
      processing was well accounted for in the SBR system as the nitrogen mass balance
      was close to 100% (97.9%).

PMID- 18325763
TI  - Psychrophilic anaerobic digestion biotechnology for swine mortality disposal.
AB  - The objective of this study was to investigate the feasibility of using
      psychrophilic anaerobic digestion in sequencing batch reactors (PADSBRs) to co
      digest grinded swine carcasses and swine manure slurry at 20 degrees C and 25
      degrees C. The PADSBRs were operated on two-week and four-week treatment cycle
      lengths, which included the fill, react, and draw phases. Two carcass loading
      rates (CLRs) were tested, that is 20 and 40g of carcass per litre of manure,
      which were equivalent to 4 and 8 times, respectively, the normal mortality rate
      on commercial farms. The PADSBR performance was compared to that of PADSBRs
      operated at 25 degrees C and fed manure only. The addition of swine carcass to
      PADSBR feed did not affect the stability of the bioreactors at both CLRs. The
      performance of the PADSBRs co-digesting swine carcasses was not statistically
      different from the control in terms of biogas production and quality. There was
      no accumulation of volatile fatty acids in the bioreactors at the end of the
      treatment cycle. The mixed-liquor pH and alkalinity remained within acceptable
      ranges for the anaerobic microflora. Also, there was no operational problem
      caused by the formation of foam and scum in the system.

PMID- 18325764
TI  - Biosynthesis of polyhydroxyalkanoate copolymers from mixtures of plant oils and 3
      hydroxyvalerate precursors.
AB  - The combination of plant oils and 3-hydroxyvalerate (3HV) precursors were
      evaluated for the biosynthesis of polyhydroxyalkanoate (PHA) copolymers
      containing 3HV monomers by Cupriavidus necator H16. Among various mixtures of
      plant oils and 3HV-precursors, the mixture of palm kernel oil and sodium
      propionate was suitable for the biosynthesis of high concentration of PHA (6.8gL(
      1)) containing 7mol% of 3HV. The 3HV monomer composition can be regulated in the
      range of 0-23mol% by changing culture parameters such as the initial pH, and the
      nitrogen source and its concentration. PHA copolymers with high weight-average
      molecular weights (Mw) ranging from 1,400,000 to 3,100,000Da were successfully
      produced from mixtures of plant oils and 3HV-precursors. The mixture of plant
      oils and sodium propionate resulted in PHA copolymers with higher M(w) compared
      to the mixture of plant oils and sodium valerate. DSC analysis on the PHA
      containing 3HV monomers showed the presence of two distinct melting temperature
      (Tm), which indicated that the PHA synthesized might be a blend of P(3HB) and
      P(3HB-co-3HV). Sodium propionate appears to be the better precursor of 3HV than
      sodium valerate.

PMID- 18325765
TI  - Phosphorus availability to maize as influenced by organic manures and fertilizer
      P associated phosphatase activity in soils.
AB  - Laboratory incubation and green house studies were conducted to compare the P
      availability of organic manures and P uptake from organic manures by maize.
      Various organic manures viz. Poultry manure (PM), Farmyard manure (FYM), Green
      manure (GM) and Crop residue (CR) and graded levels of fertilizer P were applied
      in Samana sandy loam and Ladhowal silt loam soils and incubated for 7, 15, 30, 60
      and 90 days. Samples were analyzed for P availability, P uptake and alkaline
      phosphatase activity. The overall, phosphatase activity, Paranitrophenyl
      phosphate (PNP h(-1)g(-1)), in the Ladhowal silt loam soil was higher than in the
      Samana sandy loam soil. As the level of inorganic P increased, the release of PNP
      h(-1)g(-1) soil also increased. Among different organic manures, PM registered
      the highest enzyme activity followed by FYM, GM and CR. Compared to 7 days
      incubation a slightly higher increase in PNP was noticed in samples from 90 days
      incubation in both soils. The differential phosphatase activity in the organic
      manures was further reflected in dynamic P availability. The highest amount of
      Olsen extractable P was in PM-treated soil followed by FYM, GM and field pea crop
      residue. Organic manure addition along with inorganic P, irrespective of the
      source, increased the Olsen extractable P throughout the incubation period. Total
      P uptake by maize increased with the increasing level of inorganic P in both
      soils. The highest uptake was obtained in PM-treated soil and lowest in the CR
      amended soil. We conclude that PM more readily supplies P to plants than other
      organic manure sources.

PMID- 18325766
TI  - Solid-phase synthesis of new pyrrolobenzodiazepine-chalcone conjugates: DNA
      binding affinity and anticancer activity.
AB  - A new class of C8-linked pyrrolo[2,1-c][1,4]benzodiazepine-chalcone conjugates
      have been prepared by employing a solid-phase synthetic protocol. In this
      strategy an intramolecular aza-Wittig reductive cyclization approach has been
      utilized. Interestingly, some of these molecules have shown enhanced DNA-binding
      affinity and promising anticancer activity on a large number of human cancer cell
      lines.

PMID- 18325767
TI  - Xylose as a carrier for boron containing compounds.
AB  - A xylosylated carborane was synthesized by standard carbohydrate methodology and
      tested on normal HFL-1 cells as well as transformed T24 cells. The xylosylated
      carborane initiated glycosaminoglycan (GAG) synthesis in both cell lines and
      treatment with the carborane gave a pronounced translocation of proteoglycans to
      the nuclei of T24 cells. However, most of the boron-containing compounds were
      secreted to the medium. We conclude that xylosides carrying carboranes are not
      suitable for boron neutron capture therapy (BNCT) for T24 cells. However, the
      uptake of boron-containing xyloside, the GAG priming capacity, and the nuclear
      translocation of glypican-1 make this xyloside a candidate for further
      investigation for selectivity toward other tumor cell lines.

PMID- 18325768
TI  - The design and synthesis of novel alpha-ketoamide-based p38 MAP kinase
      inhibitors.
AB  - We have identified a novel series of potent p38 MAP kinase inhibitors through
      structure-based design which due to their extended molecular architecture bind,
      in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo
      PK studies show these compounds to have drug-like characteristics which could
      result in the development of an oral treatment for inflammatory conditions.

PMID- 18325769
TI  - SUNCT and SUNA: clinical features and medical treatment.
AB  - Short-lasting unilateral neuralgiform headache with conjunctival injection and
      tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with
      cranial autonomic symptoms (SUNA) are considered to be rare primary headache
      disorders. The purpose of this study was to define the clinical features,
      response to prophylactic treatment and efficacy of lignocaine by subcutaneous
      infusion for periods of acute exacerbation requiring hospitalisation. Over a
      period of 6 years (March 2000--February 2006) all cases of SUNCT and SUNA in
      neurology clinics at the Gold Coast Hospital, Australia, were reviewed.
      International Headache Society diagnostic criteria were used. Clinical features
      and response to treatment were prospectively recorded using headache diaries and
      magnetic resonance imaging of the brain was carried out. Twenty-four subjects
      with SUNCT or SUNA were identified. The incidence of these conditions was
      1.2/100,000 and the prevalence 6.6/100,000. An episodic disease course was
      evident in 14/24 (58%) cases, whereas 10/24 (42%) had a chronic course. An
      aberrant vessel in close association with the fifth cranial nerve was seen in 88%
      of cases. A good or excellent response to lamotrigine was seen in 11/19 (58%) and
      was more effective in the episodic group (100%). A subcutaneous infusion of
      lignocaine proved completely effective on 11/14 (78%) occasions. SUNCT and SUNA
      are not rare conditions. Characterisation into episodic and chronic disease
      course appears to be of prognostic and therapeutic importance. Lamotrigine is
      effective in the majority of cases and subcutaneous lignocaine is useful as acute
      treatment for severe recalcitrant attacks.

PMID- 18325770
TI  - Midterm comparison of posterior cruciate-retaining versus -substituting total
      knee arthroplasty using the Genesis II prosthesis. A multicenter prospective
      randomized clinical trial.
AB  - The purpose of the current study was to compare midterm outcomes of posterior
      cruciate-retaining (CR) versus posterior cruciate-substituting (PS) procedures
      using the Genesis II total knee arthroplasty (TKA) system (Smith and Nephew,
      Memphis, TN). Ninety-nine (99) CR and 93 PS TKA's were analyzed in this
      prospective, randomized clinical trial. Surgeries were performed at seven medical
      centers by participating surgeons. Clinical outcomes (Knee Society Score, Range
      of Motion, WOMAC, SF-12, and Radiographic Findings), in addition to postoperative
      complications, were evaluated with a minimum follow-up of 5 years. Following data
      analysis, there were no significant differences in patient demographics or
      preoperative clinical measures between the two groups. At the latest follow-up
      interval, no significant differences were found between the CR and PS groups with
      regards to functional assessment, patient satisfaction, or postoperative
      complication. However, the PS group did display statistically significant
      improvements in range of motion when compared with the CR group. The results of
      this investigation would suggest that, while comparable in regards to supporting
      good clinical outcomes, the PS Genesis II design does appear to support
      significantly improved postoperative range of motion when compared with the CR
      design.

PMID- 18325771
TI  - Novel 3-aroylpyrazolo[5,1-c][1,2,4]benzotriazine 5-oxides 8-substituted, ligands
      at GABAA/benzodiazepine receptor complex: synthesis, pharmacological and
      molecular modeling studies.
AB  - The synthesis and binding studies of a series of 3-acylpyrazolo[5,1
      c][1,2,4]benzotriazine 5-oxides 8-substituted are reported. High-affinity ligands
      at benzodiazepine site on GABA(A) receptor complex (GABA(A)/BzR complex) were
      obtained when the 3-aroyl substituent is represented by a five-member heteroaroyl
      ring (furoyl-, thenoyl-, and pyrroyl-). Moreover the type of heteroaroyl ring at
      position 3 influences the feature of the substituent at position 8 to obtain high
      affinity ligands: a 'hydrogen-bond acceptor ring' at position 3 is synergic with
      an electron donor substituent at position 8, while a 'hydrogen-bond donor ring'
      is synergic with a withdrawing substituent. Compounds 8a, 9b, and 11 were deeply
      studied in vivo for their pharmacological effects considering six potential
      benzodiazepine actions: motor coordination, anticonvulsant action, spontaneous
      motor activity and explorative activity, anxiolytic-like effects, mouse learning
      and memory modulation, and ethanol-potentiating action. To rationalize and
      qualitatively interpret the GABA(A)/Bz binding affinities of compounds 8a and 11,
      a dynamic molecular modeling study has been performed, with the aim of assessing
      the preferred geometry of protein-ligand complex.

PMID- 18325772
TI  - A class of novel nitronyl nitroxide labeling basic and acidic amino acids:
      synthesis, application for preparing ESR optionally labeling peptides, and
      bioactivity investigations.
AB  - Aimed at optional ESR label 2-(4'-hydroxyl)phenyl-4,4,5,5-tetramethylimidazoline
      3-oxide-1-oxyl was introduced into the guanido of L-Arg-OH, the omega-amino group
      of L-Lys-OH with methylcarboxyl as a linker, and into the beta-carboxyl of L-Asp
      OH and the gamma-carboxyl of L-Glu-OH with ethylamino as a linker. It was
      explored that the synthetic 30 novel ESR labeling amino acid derivatives were
      stable enough to the reaction conditions of peptide synthesis. Their
      incorporation led to 12 novel ESR optionally labeling PAK, RGDS, RGDV, and ECG. A
      series of NO related chemical tests, the in vitro and in vivo assays of these
      peptides confirmed that this strategy was practical.

PMID- 18325773
TI  - Radioautographic study of the seasonal distribution of leukocytes in turtles
      Phrynops hilarii (Chelonia Chelidae).
AB  - The aim of this study was to present a morphological description of the
      leukocytes of Phrynops hilarii turtles according to the seasonal distribution of
      these cells and to show their replacement in the blood circulation using a
      radioautographic method. Five animals of both sexes weighing 600-1200 g were
      used. The animal's blood was aspirated, smeared on glass slides, and stained with
      the Romanowsky stain, and 500 cells of each animal were counted during each
      season. The results obtained were analyzed statistically by analysis of variance
      followed by the Bonferroni test (NCSS), with the level of significance set at
      p<0.05. The radioautographic analysis of turtle blood exposed to 1000 microCi of
      (3)H-thymidine and developed after 30 days showed a large number of silver grains
      incorporated into the cells, except for basophils, with cell renewal occurring
      every seven days. Quantitative data demonstrated a seasonal influence on the
      distribution of some leukocyte types, with the following "p" values: heterophils
      (p=0.0007), basophils (p=0.0002), monocytes (p=0.0016), eosinophils (p=0.0073).
      However, using this statistical method, it was not possible to detect a
      significant difference related to seasonal influence on lymphocytes (p=0.16295)
      or thrombocytes (p=0.1046). Using this experimental animal model, a seasonal
      influence on the distribution of some leukocyte types was observed, and the
      radioautographic method revealed a cell renewal system occurring every seven
      days, except for basophils.

PMID- 18325774
TI  - Neutron capture cross-section measurement for the 186W(n,gamma)187W reaction at
      0.0536eV energy.
AB  - The thermal neutron-induced activation cross section for the
      (186)W(n,gamma)(187)W reaction was measured at 0.0536eV neutron energy using
      TRIGA Mark-II research reactor, Atomic Energy Research Establishment, Savar,
      Dhaka, Bangladesh. The (197)Au(n,gamma)(198)Au monitor reaction induced in a high
      purity gold foil was used to determine the effective neutron beam intensity. The
      activities induced in sample and monitor foils were measured nondestructively by
      a high-resolution HPGe gamma-ray detector. The present experimental cross-section
      value is the first one at 0.0536eV. The obtained new cross section that amounts
      to 26.6+/-1.6b is 2% higher than the recently reported data in ENDF/B-VII and 5%
      lower than that of JENDL-3.3.

PMID- 18325775
TI  - Redox proteomic identification of 4-hydroxy-2-nonenal-modified brain proteins in
      amnestic mild cognitive impairment: insight into the role of lipid peroxidation
      in the progression and pathogenesis of Alzheimer's disease.
AB  - Numerous investigations point to the importance of oxidative imbalance in
      mediating AD pathogenesis. Accumulated evidence indicates that lipid peroxidation
      is an early event during the evolution of the disease and occurs in patients with
      mild cognitive impairment (MCI). Because MCI represents a condition of increased
      risk for Alzheimer's disease (AD), early detection of disease markers is under
      investigation. Previously we showed that HNE-modified proteins, markers of lipid
      peroxidation, are elevated in MCI hippocampus and inferior parietal lobule
      compared to controls. Using a redox proteomic approach, we now report the
      identity of 11 HNE-modified proteins that had significantly elevated HNE levels
      in MCI patients compared with controls that span both brain regions:
      Neuropolypeptide h3, carbonyl reductase (NADPH), alpha-enolase, lactate
      dehydrogenase B, phosphoglycerate kinase, heat shock protein 70, ATP synthase
      alpha chain, pyruvate kinase, actin, elongation factor Tu, and translation
      initiation factor alpha. The enzyme activities of lactate dehydrogenase, ATP
      synthase, and pyruvate kinase were decreased in MCI subjects compared with
      controls, suggesting a direct correlation between oxidative damage and impaired
      enzyme activity. We suggest that impairment of target proteins through the
      production of HNE adducts leads to protein dysfunction and eventually neuronal
      death, thus contributing to the biological events that may lead MCI patients to
      progress to AD.

PMID- 18325776
TI  - Harvest technique for pedicled transposition of latissimus dorsi muscle: an old
      trade revisited.
AB  - Transposition of extrathoracic muscle flaps has been the cornerstone of treatment
      of a number of complex intrathoracic pathologies such as bronchopleural fistulas
      and residual infected pleural spaces. We present a simple step-wise technique for
      preservation and harvesting of the most common muscle flap employed by thoracic
      surgeons, namely latissimus dorsi, just prior to performing a standard
      posterolateral thoracotomy. Since 2004, we have successfully utilized pedicled
      latissimus muscle as our preferred prophylactic flap against development of
      postoperative bronchopleural fistulas or recurrent empyemas. This technique
      should be part of every thoracic surgeon's surgical armamentarium.

PMID- 18325778
TI  - Genotoxicity of visible light (400-800 nm) and photoprotection assessment of
      ectoin, L-ergothioneine and mannitol and four sunscreens.
AB  - This study was designed to determine the genotoxic effects of visible (400-800nm)
      and ultraviolet A (UVA)/visible (315-800nm) lights on human keratinocytes and CHO
      cells. The alkaline comet assay was used to quantify DNA-damage. In addition,
      photo-dependent cytogenetic lesions were assessed in CHO cells by the
      micronucleus test. Three protective compounds [ectoin, l-ergothioneine (ERT) and
      mannitol] were tested with the comet assay for their effectiveness to reduce DNA
      single-strand breaks (SSB). Finally, the genomic photoprotections of two broad
      band sunscreens and their tinted analogues were assessed by the comet assay. The
      WST-1 cytotoxicity assay revealed a decrease of the keratinocyte viability of 30%
      and 13% for the highest UVA/visible and visible irradiations (15 and 13.8J/cm(2),
      respectively). Visible as well as UVA/visible lights induced DNA SSB and
      micronuclei, in a dose-dependent manner. The level of DNA breakage induced by
      visible light was 50% of the one generated by UVA/visible irradiation. However,
      UVA radiations were 10 times more effective than visible radiations to produce
      SSB. The DNA lesions induced by visible and UVA/visible lights were reduced after
      a 1-h preincubation period with the three tested compounds. The maximal
      protective effects were 92.7%, 97.9% and 52.0% for ectoin (0.1mM), ERT (0.5mM)
      and mannitol (1.5mM), respectively, against visible light and 68.9%, 59.8% and
      62.7% for ectoin (0.1mM), ERT (0.5mM) and mannitol (1.5mM), respectively, against
      UVA/visible light. Thus, visible light was genotoxic on human keratinocytes and
      CHO cells through oxidative stress mechanisms similar to the ones induced by UVA
      radiations. The four tested sunscreens efficiently prevented DNA lesions that
      were induced by both visible and UVA/visible irradiations. The tinted sunscreens
      were slightly more effective that their colorless analogues. There is a need to
      complement sunscreen formulations with additional molecules to obtain a complete
      internal and external photoprotection against both UVA and visible lights.

PMID- 18325779
TI  - Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and
      caspase-7 over-expression in spinal cord of neuropathic rats.
AB  - The effect of the non-selective, 1-aminoindan-1,5-dicarboxylic acid (AIDA), and
      selective (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl)
      methanone (JNJ16259685), metabotropic glutamate subtype 1 (mGlu1) receptor
      antagonists, on rat sciatic nerve chronic constrictive injury (CCI)-induced
      hyperalgesia, allodynia, spinal dorsal horn apoptosis, and gliosis was examined
      at 3 and 7 days post-injury. RT-PCR analysis showed increased expression of bax,
      apoptotic protease-activating factor-1 (apaf-1), nestin, GFAP, and caspase-7 mRNA
      in the dorsal horn spinal cord by 3 days post-CCI. At 7 days post-CCI, only over
      expression of bcl-2, nestin and GFAP mRNA was observed. Administration of AIDA
      reduced thermal hyperalgesia and mechanical allodynia at 3 and 7 days post-CCI;
      administration of JNJ16259685 reduced thermal hyperalgesia at 3 and 7 days post
      CCI, but not mechanical allodynia. AIDA decreased the mRNA levels of bax, apaf-1,
      GFAP and caspase-7 genes. JNJ16259685 increased the mRNA levels of bcl-2 and GFAP
      gene, and decreased APAF-1 and caspases-7 genes. Inhibiting mGlu1 receptors also
      reduced TUNEL-positive profiles and immunohistochemical reactivity for caspase-7.
      We report here that despite inhibiting CCI-induced over-expression of pro
      apoptotic genes in the spinal cord dorsal horn, the selective mGlu1 receptor
      antagonist JNJ16259685 exerted only a slight and transient allodynic effect.
      Moreover, JNJ16259685, but not the non-selective AIDA, increased astrogliosis
      which may account for its decreased analgesic efficacy. This study provides
      evidence that the contemporary and partial blockade of group I and likely
      ionotropic glutamate receptors may be a more suitable therapy than selective
      blockade of mGlu1 subtype receptors condition to decrease neuropathic pain
      symptoms.

PMID- 18325780
TI  - Pharmacokinetics of fructose-1,6-diphosphate after intraperitoneal and oral
      administration to adult rats.
AB  - Exogenously administered fructose-1,6-diphosphate (FDP) has been studied for its
      ability to protect tissue during hypoxia or ischemia. Recently, a clear effect of
      FDP on the central nervous system has raised the question whether FDP can get
      into the brain. FDP levels were measured in blood, brain, liver, kidney, muscle
      and fat after intraperitoneal administration of a single 0.5gkg(-1) dose of FDP
      to adult male Sprague-Dawley rats. A complete time course of the levels in blood
      and brain was determined. The levels of FDP in the blood and brain increase
      simultaneously, i.e. there is no lag in the increase in the brain. The levels of
      FDP fall to baseline in liver, kidney, muscle and fat by 12h, but remain elevated
      in blood and brain. However, levels in the blood at 12h are significantly
      decreased from the peak levels, while those in brain are not different from the
      peak levels, suggesting that the kinetics of FDP in blood and brain are quite
      different. Stripping the endothelial cells from the brain tissue sample did not
      change the levels of FDP indicating that FDP is not trapped in the capillary
      cells. Incubation of brain slices in a solution of FDP, followed by washing,
      raised tissue levels of FDP indicating that FDP is taken up into cells within the
      brain. Finally, the experiments demonstrate a significant increase in brain
      levels of FDP after oral administration. These data suggest that an oral
      formulation of FDP might be developed for treatment of neurological disease.

PMID- 18325781
TI  - Relative importance of basicity in the gas phase and in solution for determining
      selectivity in electrospray ionization mass spectrometry.
AB  - Electrospray ionization mass spectrometry is a critically important technique for
      the determination of small molecules, but its application for this purpose is
      complicated by its selectivity. For positive ion ESI-MS analysis of basic
      analytes, several investigators have pointed to the importance of analyte
      basicity as a source of selectivity. Currently, however, it is not known whether
      basicity in the gas phase or in solution is ultimately most important in
      determining responsiveness. The objective of these studies was to investigate the
      relative importance of basicity in solution and in the gas phase as factors that
      predict selectivity in positive ion ESI-MS analysis. ESI-MS response was compared
      for a diverse series of protonatable analytes in two different solvents, neat
      methanol and methanol with 0.5% acetic acid. A correlation was observed between
      analyte pK(b) and electrospray response. However, the response for the analytes
      with very high pK(b) values was significantly higher than would be expected based
      on concentration of the protonated form or the analyte in solution, and this
      higher response did not appear to result from gas-phase proton transfer
      reactions. Although all of the analytes investigated had higher gas-phase
      basicities than the solvent, their relative responses were not dictated by gas
      phase basicity. Higher response was observed for all of the analytes studied in
      acidified methanol compared with neat methanol, and this higher response was most
      pronounced for weakly basic analytes. These findings support the use of analyte
      pK(b) for rational method development in ESI-MS analysis of small molecules.

PMID- 18325782
TI  - A model-based method for the prediction of the isotopic distribution of peptides.
AB  - The process of monoisotopic mass determination, i.e., nomination of the correct
      peak of an isotopically resolved group of peptide peaks as a monoisotopic peak,
      requires prior information about the isotopic distribution of the peptide. This
      points immediately to the difficulty of monoisotopic mass determination, whereas
      a single mass spectrum does not contain information about the atomic composition
      of a peptide and therefore the isotopic distribution of the peptide remains
      unknown. To solve this problem a technique is required, which is able to estimate
      the isotopic distribution given the information of a single mass spectrum. Senko
      et al. calculated the average isotopic distribution for any mass peptide via the
      multinomial expansion (Yergey 1983), using a scaled version of the average amino
      acid Averagine (Senko et al. 1995). Another method, introduced by Breen et al.,
      approximates the result of the multinomial expansion by a Poisson model (Breen et
      al. 2000). Although both methods perform well, they have their specific
      limitations. In this manuscript, we propose an alternative method for the
      prediction of the isotopic distribution based on a model for consecutive ratios
      of peaks from the isotopic distribution, similar in spirit to the approach
      introduced by Gay et al. (1999). The presented method is computationally simple
      and accurate in predicting the expected isotopic distribution. Further, we extend
      our method to estimate the isotopic distribution of sulphur-containing peptides.
      This is important because the naturally occurring isotopes of sulphur have an
      impact on the isotopic distribution of a peptide.

PMID- 18325783
TI  - Use of 157-nm photodissociation to probe structures of y- and b-type ions
      produced in collision-induced dissociation of peptide ions.
AB  - y- and b-type fragment ions produced in the collisional dissociation of arginine
      terminated peptide ions are photodissociated with 157-nm light in a linear trap.
      y-type ions are shown to have the same structure as that of intact peptides of
      the same sequence with the ionizing proton located at the most basic residue(s).
      For generic b-type ions, the ionizing proton is shown to be sequestered at the N
      terminal arginine, which is consistent with the proposed oxazolone structure.

PMID- 18325784
TI  - PNUTS forms a trimeric protein complex with GABA(C) receptors and protein
      phosphatase 1.
AB  - Phosphorylation and dephosphorylation of neurotransmitter receptors represent an
      important mechanism to regulate synaptic signal transduction. Here, we identified
      PNUTS, a targeting subunit of protein phosphatase 1 (PP1) as a new binding
      partner of GABA(C) receptors. In the mammalian retina, PNUTS is co-expressed with
      GABA(C) receptors and PP1 in bipolar cells. PNUTS and PP1 were detected in
      membrane protein preparations of the retina and precipitate with GABA(C) receptor
      specific antibodies. Furthermore, PNUTS shuttles from the nucleus to the membrane
      in cells co-expressing GABA(C) receptors. We show simultaneous binding of PP1 and
      GABA(C) receptors to different domains of PNUTS, demonstrating that PNUTS cross
      links PP1 and GABA(C) receptors. Finally, modeling studies showed that the PP1
      docking motif of PNUTS fits into the binding pocket on the enzyme surface,
      despite a C-terminal adjacent proline. We suggest that PNUTS targets PP1 to
      synaptic sites, acting as a temporary bridge between the phosphatase and GABA(C)
      receptors.

PMID- 18325785
TI  - Pathogenic mutations in the glycosylphosphatidylinositol signal peptide of PrP
      modulate its topology in neuroblastoma cells.
AB  - Point mutations M232R (PrP(232R)), M232T (PrP(232T)), and P238S (PrP(238S)) in
      the glycosylphosphatidylinositol signal peptide (GPI-SP) of the prion protein
      (PrP(C)) segregate with familial Creutzfeldt-Jakob disease (CJD). However, the
      mechanism by which these mutations induce cytotoxicity is unclear since the GPI
      SP is replaced by a GPI anchor within 5 min of PrP synthesis and translocation
      into the endoplasmic reticulum (ER). To examine if mutations in this region
      interfere with translocation of nascent PrP into the ER or anchor addition, the
      metabolism of PrP(232R) and PrP(232T) was investigated in transfected human
      neuroblastoma cells. In this report, we demonstrate that PrP mutations M232R and
      M232T do not interfere with GPI anchor addition. Instead, these mutations
      increase the stability and transport of GPI-SP mediated post-translationally
      translocated PrP to the plasma membrane, where it is linked to the lipid bilayer
      in a potentially neurotoxic C-transmembrane ((Ctm)PrP) orientation. Furthermore,
      we demonstrate that the GPI-SP of PrP functions as an efficient co-translational
      and inefficient post-translational ER translocation signal when tagged to an
      unrelated protein, underscoring the functional versatility of this peptide. These
      data uncover an alternate pathway of ER translocation for nascent PrP, and
      provide information on the possible mechanism(s) of neurotoxicity by mutations in
      the GPI-SP.

PMID- 18325786
TI  - Structural and kinetic contributions of the oxyanion binding site to the
      catalytic activity of acylaminoacyl peptidase.
AB  - It is widely accepted that the catalytic activity of serine proteases depends
      primarily on the Asp-His-Ser catalytic triad and other residues within the
      vicinity of this motif. Some of these residues form the oxyanion binding site
      that stabilizes the tetrahedral intermediate by hydrogen bonding to the
      negatively charged oxyanion. In acylaminoacyl peptidase from the thermophile
      Aeropyrum pernix, the main chain NH group of Gly369 is one of the hydrogen bond
      donors forming the oxyanion binding site. The side chain of His367, a conserved
      residue in acylaminoacyl peptidases across all species, fastens the loop holding
      Gly369. Determination of the crystal structure of the H367A mutant revealed that
      this loop, including Gly369, moves away considerably, accounting for the observed
      three orders of magnitude decrease in the specificity rate constant. For the wild
      type enzyme ln(k(cat)/K(m)) vs. 1/T deviates from linearity indicating greater
      rate enhancement with increasing temperature for the dissociation of the enzyme
      substrate complex compared with its decomposition to product. In contrast, the
      H367A variant provided a linear Arrhenius plot, and its reaction was associated
      with unfavourable entropy of activation. These results show that a residue
      relatively distant from the active site can significantly affect the catalytic
      activity of acylaminoacyl peptidase without changing the overall structure of the
      enzyme.

PMID- 18325787
TI  - Distinct horizontal patterns in the spatial organization of superficial zone
      chondrocytes of human joints.
AB  - A better understanding of the unique cellular and functional properties of the
      superficial zone of articular cartilage may aid current strategies in tissue
      engineering which attempts a layered design for the repair of cartilage lesions
      to avert or postpone the onset of osteoarthritis. However, data pertaining to the
      cellular organization of non-degenerated superficial zone of articular cartilage
      is not available for most human joints. The present study analyzed the
      arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow,
      knee, and ankle) by using fluorescence microscopy of the superficial zone in a
      top-down view. The resulting horizontal chondrocyte arrangements were tested for
      randomness, homogeneity or a significant grouping via point pattern analysis and
      were correlated with the joint type in which they occurred. The present study
      demonstrated that human superficial chondrocytes occurred in four distinct
      patterns of strings, clusters, pairs or single chondrocytes. Those patterns
      represented a significant grouping (p < 0.0001) with horizontal alignment. Each
      articular joint surface was dominated by only one of these four patterns (p <
      0.001). Specific patterns correlated with specific diarthrodial joint types (p <
      0.001). Further studies need to establish whether these organizational patterns
      are a consequence of their surrounding environment or whether they are linked to
      a functional purpose.

PMID- 18325788
TI  - How to test the threat-simulation theory.
AB  - Malcolm-Smith, Solms, Turnbull and Tredoux [Malcolm-Smith, S., Solms,
      M.,Turnbull, O., & Tredoux, C. (2008). Threat in dreams: An adaptation?
      Consciousness and Cognition, 17, 1281-1291.] have made an attempt to test the
      Threat-Simulation Theory (TST), a theory offering an evolutionary psychological
      explanation for the function of dreaming [Revonsuo, A. (2000a). The
      reinterpretation of dreams: An evolutionary hypothesis of the function of
      dreaming. Behavioral and Brain Sciences, 23(6), 877-901]. Malcolm-Smith et al.
      argue that empirical evidence from their own study as well as from some other
      studies in the literature does not support the main predictions of the TST: that
      threatening events are frequent and overrepresented in dreams, that exposure to
      real threats activates the threat-simulation system, and that dream threats
      contain realistic rehearsals of threat avoidance responses. Other studies,
      including our own, have come up with results and conclusions that are in conflict
      with those of Malcolm-Smith et al. In this commentary, we provide an analysis of
      the sources of these disagreements, and their implications to the TST. Much of
      the disagreement seems to stem from differing interpretations of the theory and,
      consequently, of differing methods to test it.

PMID- 18325789
TI  - Effects of shifting perspective of the self: an fMRI study.
AB  - When looking to our reflection, or moving a video-game character, we see our own
      movement preformed by an agent which is physically separated from our body. Yet,
      we consider the agent to be ourself. Using fMRI, we sought to explore the neural
      underpinnings of disembodiment, the cognitive mechanism under which the
      properties of the self are projected away from the boundaries of one's own body
      towards an external entity. Seventeen participants watched a video-game in which
      three players threw each other a ball. Subjects' key-press could either be
      synchronous or asynchronous with one of the players' action (TASK: Agency vs.
      Control). The game was shown from one of four viewpoints which could either be
      fixed or change every trial (VIEWS: Fixed vs. Changeable). Consistent with
      previous studies, the left insula was activated when the agent's movements were
      synchronous with those of the participants (main effect of TASK, p<0.05, SVC).
      The analysis of the interaction TASKVIEWS revealed activation (p<0.05, corrected)
      of the right parieto-temporal-occipital (PTO) junction when the agent whose
      movements were synchronous to the participants was processed in a spatial
      position each time different with respect to the preceding trials. Our findings
      implicate the right PTO junction in assigning one's own movements to an agent
      which is physically independent of oneself. They also suggest that the ability to
      disembody, and thereby objectify, bodily or mental states concerning the self is
      common to all experimental paradigms which led to an activation of the PTO
      junction.

PMID- 18325790
TI  - Voxel-based cortical thickness measurements in MRI.
AB  - The thickness of the cerebral cortex can provide valuable information about
      normal and abnormal neuroanatomy. High resolution MRI together with powerful
      image processing techniques has made it possible to perform these measurements
      automatically over the whole brain. Here we present a method for automatically
      generating voxel-based cortical thickness (VBCT) maps. This technique results in
      maps where each voxel in the grey matter is assigned a thickness value. Sub-voxel
      measurements of thickness are possible using sub-sampling and interpolation of
      the image information. The method is applied to repeated MRI scans of a single
      subject from two MRI scanners to demonstrate its robustness and reproducibility.
      A simulated data set is used to show that small focal differences in thickness
      between two groups of subjects can be detected. We propose that the analysis of
      VBCT maps can provide results that are complementary to other anatomical analyses
      such as voxel-based morphometry.

PMID- 18325791
TI  - A new perspective on the evolutionary history of western European Sorex araneus
      group revealed by paternal and maternal molecular markers.
AB  - The species of the common shrew (Sorex araneus) group are morphologically very
      similar, but have undergone a spectacular chromosomal evolution. We investigate
      here the evolutionary history of the Sorex araneus group distributed in western
      Europe. In particular, we clarify the position of a difficult species, S.
      granarius, using sex-specific (mtDNA and Y-chromosome) markers. The karyotype of
      S. granarius is generally considered similar to the common ancestor of the
      restricted group considered here. The mtDNA data (1.4 kb) confirms the close
      relationship between S. granarius and S. araneus sensu stricto (hereafter S.
      araneus s.s.), but the Y-chromosome (3.4 kb) produces a quite different picture:
      S. granarius is closely related to another species, S. coronatus. Comparison of
      mtDNA and Y-chromosome phylogenies suggests that the genetic and chromosomal
      evolution in this group are disconnected processes. The evolutionary history of
      the south-western European populations of the S. araneus group can only be
      understood considering secondary contacts between taxa after their divergence,
      implying genetic exchanges by means of hybridization and/or introgression.

PMID- 18325792
TI  - Phylogeny of the parasitic microgastroid subfamilies (Hymenoptera: Braconidae)
      based on sequence data from seven genes, with an improved time estimate of the
      origin of the lineage.
AB  - The microgastroid complex of braconid wasps is a widely recognized and
      biologically coherent lineage of endoparasitoids of lepidopteran larvae
      (caterpillars). The complex has received significant phylogenetic attention in
      recent years due in part to the taxons' association with mutualistic
      polydnaviruses, with which they compromise host immune systems. A number of
      previous attempts using a variety of morphological and molecular approaches have
      not unequivocally resolved relationships amongst the main subfamilies. This work
      represents a more extensive attempt to resolve the microgastroid relationships,
      using seven genes (16S rRNA, cytochrome oxidase I (CO1), 28S rRNA, arginine
      kinase (ArgK), long wavelength rhodopsin (Ops), elongation factor 1 alpha (EF1a)
      and wingless (Wg)) and a greater taxonomic representation. Bayesian, likelihood
      and parsimony phylogenetic reconstructions of this improved data set has
      determined that the chelonines diverged first from the remainder of the
      microgastroids, however the relationships amongst the other subfamilies are still
      unclear, suggesting a greater nucleotide sample is required to resolve them.
      Examination of the contribution of individual gene trees to the phylogeny
      demonstrates why the relationships between subfamilies are still unclear, with
      not all groups monophyletic for all trees. Filtered supernetworks demonstrate
      that monophyly of all subfamilies is only recovered when splits found in only one
      or two genes are excluded, but this also results in little remaining structure
      left in the deep nodes to resolve inter-subfamily relationships. By increasing
      the breadth of the study we were also able to re-evaluate previous attempts at
      dating the lineage and, therefore the origin of the polydnavirus association.
      Previous attempts used a much reduced data set and fewer fossil calibrations.
      Thorough literature searches have revealed a substantial increase in the fossil
      calibrations and these, combined with more sophisticated molecular dating
      analysis, have substantially increased the age of the microgastroid lineage from
      previous estimates of approximately 73MYA to approximately 100MYA. Examination of
      the resultant linearized clock tree also allows an insight into the evolution of
      the more species rich subfamilies. The chelonines appear to have had a steady
      rate of evolution, whilst the microgastrines and cardiochilines appear to have
      undergone a more significant "burst" of evolution. It is hypothesized that the
      different parasitism strategies of subfamilies (Chelonines are egg parasitoids
      and the remainder are larval parasitioids) may have influenced the evolutionary
      rates of the groups.

PMID- 18325793
TI  - A study on phylogeny and biogeography of mahseer species (Pisces: Cyprinidae)
      using sequences of three mitochondrial DNA gene regions.

PMID- 18325794
TI  - Dealing with incongruence in the quest for the species tree: a case study from
      the orchid genus Satyrium.
AB  - A species tree was reconstructed for the mainly African terrestrial orchid genus
      Satyrium. Separate phylogenetic analysis of both plastid and ribosomal nuclear
      DNA sequences for 63 species, revealed extensive topological conflict. Here we
      describe a detailed protocol to deal with incongruence involving three steps:
      identifying incongruence and testing its significance, assessing the cause of
      incongruence, and reconstructing the species tree. The Incongruence Length
      Difference test revealed that many cases of incongruence were non-significant.
      For the remaining significant cases, results from taxon jack-knifing experiments
      and parametric bootstrap suggested that non-biological artefacts such as sparse
      taxon sampling and long-branch attraction could be excluded as causes for the
      observed incongruence. In order to evaluate biological causes, such as
      orthology/paralogy conflation, lineage sorting, and hybridization, the number of
      events was counted that needs to be invoked a-posteriori to explain the observed
      pattern. In most cases where incongruence was significant, this resulted in a
      similar number of events for each of these different causes. Only for the three
      species from south east Asia, that form a monophyletic clade, hybridization was
      favoured over the alternative causes. This conclusion is based on the large
      number of events that needs to be invoked, in order for either orthology/paralogy
      conflation or lineage sorting to have been the cause of the
      incongruence+morphological evidence. The final species tree presented here is the
      product of the combined analysis of plastid and ITS sequences for all non
      incongruent species and a-posteriori grafting of the incongruent clades or
      accessions onto the tree.

PMID- 18325795
TI  - Evaluation of abduction range of motion and avoidance of inferior scapular
      impingement in a reverse shoulder model.
AB  - The purpose of this study was to determine the effects of prosthetic design and
      surgical technique of reverse shoulder implants on total abduction range of
      motion and impingement on the inferior scapular neck. Custom implants in three
      glenosphere diameters (30, 36, and 42 mm), with 3 different centers of rotation
      offsets (0, +5, and +10 mm), were placed into a Sawbones scapula (Pacific
      Research Laboratories, Vashon, WA) in 3 different positions: superior, center,
      and inferior glenoid. Humeral sockets were manufactured with a 130 degrees , 150
      degrees , and 170 degrees neck-shaft angle. Four independent factors (glenosphere
      diameter, center of rotation offset, glenosphere position on the glenoid, and
      humeral neck-shaft angle) were compared with the 2 dependent factors of range of
      motion and inferior scapular impingement. Center of rotation offset had the
      largest effect on range of motion, followed by glenosphere position. Neck-shaft
      angle had the largest effect on inferior scapular impingement, followed by
      glenosphere position. This information may be useful to the surgeon when deciding
      on the appropriate reverse implant.

PMID- 18325796
TI  - Osteochondritis dissecans of the glenoid associated with the nontraumatic,
      painful throwing shoulder in a professional baseball player: a case report.

PMID- 18325797
TI  - Cross-sectional anatomy of the bicipital tuberosity and biceps brachii tendon
      insertion: relevance to anatomic tendon repair.
AB  - This study evaluated the insertional anatomy and orientation of the biceps
      tuberosity and tendon to assess the anatomic validity of repairs made with 1
      incision vs 2 incisions. Computed axial tomography was used to image 30 cadaver
      radii, and each tendon insertion was measured with a digital micrometer.
      Specimens were sectioned and imaged with Faxitron radiography (Faxitron X-Ray
      Corp, Wheeling, IL) to determine the angular orientation of the biceps tendon
      insertion relative to the tuberosity apex. The tuberosity axis of orientation
      averaged 65 degrees (range, 15 degrees -120 degrees ) of pronation from anterior,
      with angular orientation encompassing a mean 59 degrees (range, 15 degrees -100
      degrees ) arc with the midpoint of the insertion averaging 50 degrees (range, -5
      degrees to 105 degrees ). Most biceps tendons inserted on the anterior aspect of
      the apex of the tuberosity, with an average width of 7 mm and length of 22 mm.
      The biceps tuberosity is oriented in more pronation than is typically described,
      prohibiting anatomic reinsertion of the tendon in 35% of specimens with current
      single-incision techniques.

PMID- 18325799
TI  - Does the 'high risk' patient with asymptomatic carotid stenosis really exist?
AB  - Recent evidence indicates that the risk of stroke symptoms in non-operated
      medically managed patients with asymptomatic severe carotid stenosis has fallen
      significantly over the last 25 years. This suggests concurrent improvements in
      vascular disease medical intervention efficacy. If the latest estimates of
      average annual stroke rate for non-operated patients are reflective of
      contemporary medical intervention and surgical stroke/death rates match those of
      the randomised trials, the current implication is that carotid surgery will not
      offer a stroke prevention advantage over medical intervention alone. Furthermore,
      it is still not possible to identify patients with asymptomatic severe carotid
      stenosis with a higher than average ipsilateral stroke risk despite current
      medical intervention. Even if such patients were one day reliably identified,
      they could also be at higher risk of stroke/death from instrumental intervention
      (surgery, angioplasty or stenting) and randomised trials will be required before
      being justification in routine clinical practice.

PMID- 18325801
TI  - Role of antioxidants and trace elements in health and immunity of transition
      dairy cows.
AB  - A number of antioxidants and trace minerals have important roles in immune
      function and may affect health in transition dairy cows. Vitamin E and beta
      carotene are important cellular antioxidants. Selenium (Se) is involved in the
      antioxidant system via its role in the enzyme glutathione peroxidase. Inadequate
      dietary vitamin E or Se decreases neutrophil function during the perpariturient
      period. Supplementation of vitamin E and/or Se has reduced the incidence of
      mastitis and retained placenta, and reduced duration of clinical symptoms of
      mastitis in some experiments. Research has indicated that beta-carotene
      supplementation may enhance immunity and reduce the incidence of retained
      placenta and metritis in dairy cows. Marginal copper deficiency resulted in
      reduced neutrophil killing and decreased interferon production by mononuclear
      cells. Copper supplementation of a diet marginal in copper reduced the peak
      clinical response during experimental Escherichia coli mastitis. Limited research
      indicated that chromium supplementation during the transition period may increase
      immunity and reduce the incidence of retained placenta.

PMID- 18325802
TI  - NeuroQuick--a novel bedside test for small fiber neuropathy?
AB  - BACKGROUND: An appropriate bedside test for small fiber neuropathy does not exist
      so far. Cold hypaesthesia occurs as an early onset symptom, and the new handheld
      device NeuroQuick (NQ) was recently claimed to be a valid and reliable screening
      tool for its quantitative assessment. AIMS: Comparison of the NQ with
      standardized quantitative sensory testing (QST) in patients suffering from
      chronic painful dysaesthesia with and without pathological cold detection
      threshold (CDT). METHODS: Forty-one patients with and without diabetes mellitus
      displaying chronic painful dysaesthesia were included (18 men, 55.8+/-13 years).
      According to the German network protocol QST was performed in the body area with
      the severest symptoms and at the opposite side as control after thorough clinical
      neurological examination. The NeuroQuick, developed as quantitative bedside
      testing of cold thermal perception based on the wind chill, was used
      subsequently. RESULTS: DT was pathologically increased in 14 and within normal
      range in 27 patients; NQ values were pathological in 9 and non-pathological in 32
      patients. Thus NQ obtained 7.4% false positive and 50% false negative results in
      detecting cold hypaesthesia, corresponding to 92.6% specificity, 50% sensitivity
      and a positive and negative predictive value of 78%, respectively. CONCLUSIONS:
      This study demonstrates that the NeuroQuick is not an adequate screening device
      for cold hypaesthesia in patients with chronic neuropathic pain. It exhibits a
      high specificity but only low sensitivity in the identification of such small
      fiber dysfunction; a reliable and valid screening tool should necessarily provide
      opposite features.

PMID- 18325803
TI  - Animal models of COPD: Barriers, successes, and challenges.
AB  - Animal models have definite utility in the study of chronic obstructive pulmonary
      disease. However, choice of model must be determined with the full knowledge of
      their value, or potential limitations.

PMID- 18325804
TI  - Muscle water control in crustaceans and fishes as a function of habitat,
      osmoregulatory capacity, and degree of euryhalinity.
AB  - This study aimed at detecting possible patterns in the relationship between
      Anisosmotic Extracellular Regulation (AER) and Isosmotic Intracellular Regulation
      (IIR) in crustaceans and teleost fish from different habitats and evolutionary
      histories in fresh water (FW), thus different osmoregulatory capabilities, and
      degrees of euryhalinity. Crustaceans used were the hololimnetic FW Aegla
      schmitti, and Macrobrachium potiuna, the diadromous FW Macrobrachium acanthurus,
      the estuarine Palaemon pandaliformis and the marine Hepatus pudibundus; fishes
      used were the FW Corydoras ehrhardti, Mimagoniates microlepis, and Geophagus
      brasiliensis, and the marine-estuarine Diapterus auratus. The capacity for IIR
      was assessed in vitro following wet weight changes of isolated muscle slices
      incubated in anisosmotic saline (~50% change). M. potiuna was the crustacean with
      the highest capacity for IIR; the euryhaline perciforms G. brasiliensis and D.
      auratus displayed total capacity for IIR. It is proposed that a high capacity for
      IIR is required for invading a new habitat, but that it is later lost after a
      long time of evolution in a stable habitat, such as in the FW anomuran crab A.
      schmitti, and the Ostariophysian fishes C. ehrhardti and M. microlepis. More
      recent FW invaders such as the palaemonid shrimps (M. potiuna and M. acanthurus)
      and the cichlid G. brasiliensis are euryhaline and still display a high capacity
      for IIR.

PMID- 18325805
TI  - A viral lectin encoded in Cotesia plutellae bracovirus and its immunosuppressive
      effect on host hemocytes.
AB  - An endoparasitoid wasp, Cotesia plutellae, induces immunosuppression of the host
      diamondback moth, Plutella xylostella. To identify an immunosuppressive factor,
      the parasitized hemolymph of P. xylostella was separated into plasma and hemocyte
      fractions. When nonparasitized hemocytes were overlaid with parasitized plasma,
      they showed significant reduction in bacterial binding efficacy. Here, we
      considered a viral lectin previously known in other Cotesia species as a humoral
      immunosuppressive candidate in C. plutellae parasitization. Based on consensus
      regions of the viral lectins, the corresponding lectin gene was cloned from P.
      xylostella parasitized by C. plutellae. Its cDNA is 674 bp long and encodes 157
      amino acid residues containing a signal peptide (15 residues) and one
      carbohydrate recognition domain. Open reading frame is divided by one intron (156
      bp) in its genomic DNA. Amino acid sequence shares 80% homology with that of C.
      ruficrus bracovirus lectin and is classified into C-type lectin. Southern
      hybridization analysis indicated that the cloned lectin gene was located at C.
      plutellae bracovirus (CpBV) genome. Both real-time quantitative RT-PCR and
      immunoblotting assays indicated that CpBV-lectin showed early expression during
      the parasitization. A recombinant CpBV-lectin was expressed in a bacterial system
      and the purified protein significantly inhibited the association between bacteria
      and hemocytes of nonparasitized P. xylostella. In the parasitized P. xylostella,
      CpBV-lectin was detected on the surface of parasitoid eggs after 24 h
      parasitization by its specific immunostaining. The 24 h old eggs were not
      encapsulated in vitro by hemocytes of P. xylostella, compared to newly laid
      parasitoid eggs showing no CpBV-lectin detectable and easily encapsulated. These
      results support an existence of a polydnaviral lectin family among Cotesia
      associated bracovirus and propose its immunosuppressive function.

PMID- 18325806
TI  - Changes in Na+/K+-ATPase activity, unsaturated fatty acids and metallothioneins
      in gills of the shore crab Carcinus aestuarii after dilute seawater acclimation.
AB  - We have assessed the activity of Na(+)/K(+)-ATPase, cAMP, free fatty acids (FFA)
      and metallothionein (MT) in the posterior gills of the brackish water shore crab
      Carcinus aestuarii during acclimation to 10 ppt dilute seawater (DSW). Following
      3-18 days acclimation in DSW specific activity of Na(+)/K(+)-ATPase in native
      gill homogenates and partially purified membrane vesicles was progressively
      increased, from 1.7- to 3.9-fold. After short-term acclimation of crabs in DSW
      with added sucrose to make media isosmotic with the haemolymph the specific
      Na(+)/K(+)-ATPase activity in homogenates was not increased, relative to SW
      enzyme activity. Moreover, hyposmotic conditions led to depletion of cAMP in
      gills. In partially purified membrane vesicles isolated from posterior gills,
      fatty acids with compositions 16:0, 18:0, 18:1, 20:4 and 20:5 dominated in both
      SW- and DSW-acclimated Carcinus. During a year in which the metabolic activity of
      crabs was increased, the arachidonic/linoleic acids ratio (ARA/LA) for DSW
      acclimated crabs was markedly increased relative to that in SW. Increased
      Na(+)+K(+)-ATPase activity under hyposmotic stress may be modulated at least
      partially by the changed proportion of fatty acids in the purified membranes of
      posterior gills. Long-term acclimation of shore crabs to DSW resulted in a 2.6
      fold increase in cytosolic metallothionein (MT) content in posterior gills over
      those in SW crabs. Assuming an antioxidant role of MT associated with
      intracellular zinc partitioning, the observed MT induction in posterior gills may
      be considered an adaptive response of C. aestuarii to hyposmotic stress.

PMID- 18325807
TI  - Soluble organic matrices of aragonitic skeletons of Merulinidae (Cnidaria,
      Anthozoa).
AB  - Our interpretation of the overall taxonomy and evolution of the Scleractinia, the
      most important reef builders in tropical areas, has long depended exclusively on
      morphology of the calcareous skeletons. The reported series of physical and
      biochemical characterizations of skeletons and the mineralizing matrices
      extracted from the skeletons allow, for the first time, the level of biochemical
      diversity among corallites of the same family to be estimated. Similarities and
      differences observed in the micro- and nanostructures of the skeletons reflect
      those of the soluble organic matrices. Sulphur is mainly associated with
      sulphated acidic sugars. The role of sulphated sugars on the biomineralization
      processes is still underestimated. The resulting data suggest that environmental
      conditions may act on the mineralization process through the detailed
      compositions of the mineralizing matrices.

PMID- 18325808
TI  - Abnormal expression of truncated CRMP-1 protein in the brain cortex of MPSIIIB
      mice.
AB  - Mucopolysaccharidosis IIIB is a lysosomal disease characterized by a severe
      neurological deterioration, the pathophysiological mechanisms of which are poorly
      understood. Recently FGF pathway was shown to be altered leading us to explore a
      downstream target involved in brain development: the collapsin response mediator
      protein-1 (CRMP-1). CRMP-1 transcript level was normal but a cleavage of CRMP-1
      was observed with an abnormal expression of the truncated form until adult age.
      This truncated CRMP-1 protein could play a role in post-natal cortex maturation
      and be involved in neuronal alterations occurring in lysosomal diseases.

PMID- 18325809
TI  - Gene duplications resulting in over expression of glucokinase are not a common
      cause of hypoglycaemia of infancy in humans.

PMID- 18325810
TI  - HIV and sexual risk behaviors among recognized high-risk groups in Bangladesh:
      need for a comprehensive prevention program.
AB  - OBJECTIVE: To examine trends in HIV and related risk behaviors among recognized
      high-risk groups in Bangladesh, the types and extent of prevention initiatives
      that have been undertaken, and highlight the immediate needs. METHODS: Journal
      publications and conference abstracts and proceedings were reviewed. Experts
      involved in the development and evaluation of current programs or policy were
      contacted for official reports and policy documents. The trends in sexual risk
      behaviors over five rounds of national surveillance were tabulated. Gaps in the
      ongoing prevention interventions have been assessed in the light of the Anderson
      May equation. RESULTS: Periodic surveillance on recognized high-risk groups shows
      that HIV prevalence has been increasing steadily. In the capital city, HIV
      prevalence in one subset of a high-risk group is close to the level of a
      concentrated epidemic (4.9%). The high prevalence of sexual risk behaviors among
      drug users and sex workers and their clients is alarming. Although a small
      increase in condom use and a reduction of syphilis have been noted among subsets
      of high-risk groups in recent years, this is clearly not enough to curb the
      threat of a possible HIV epidemic. CONCLUSION: There is an urgent need for a
      comprehensive prevention program that should include more efforts on education
      and condom promotion, effective management of all sexually transmitted
      infections, a screening program for migrant workers, the continuation of both
      behavioral and serological components of HIV surveillance, and the expansion of
      surveillance to cover the remaining high-risk groups, with due consideration to
      the consistency of surveillance indicators.

PMID- 18325811
TI  - Enhanced viral immunoinflammatory lesions in mice lacking IL-23 responses.
AB  - Herpes simplex virus (HSV) infection of the cornea culminates in an
      immunopathological lesion (stromal keratitis--SK) that impairs vision. This
      report shows that HSV infection results in IL-23 up-regulation, but if this
      response fails to occur, as was noted in p19-/- mice, the severity of lesions,
      their incidence and the level of viral induced angiogenesis were significantly
      increased compared to wild-type (WT) animals (p<0.05). The higher disease
      severity in p19-/- mice appeared to be the consequence of an increased IL-12
      response that in turn led to the induction of higher numbers of IFN-gamma
      producing CD4(+)T cells, the principal orchestrators of SK. Our results indicate
      that the severity of HSV induced immunopathological lesions may be mainly the
      consequence of IL-12 driven Th1 T cell reactions rather than the action of IL-17
      producing cells controlled by IL-23.

PMID- 18325812
TI  - [Paralysis of the intrinsic muscles of the hand].
AB  - Intrinsic muscles of the fingers are the interosseous, lumbricals and hypothenar
      muscles. Their main action is metacarpophalangeal (MP) flexion and
      interphalangeal (IP) extension. If extrinsic muscles remain active, intrinsic
      paralysis results in a claw deformity: MP hyperextension and IP flexion.
      Bouvier's test is positive if IP extension is actively possible when MP
      hyperextension is passively prevented. Surgical operations to correct claw
      deformity are divided into passive and active palliative procedures. Passive
      palliative procedures are tenodeses and capsuloplasties. Active palliative
      procedures have either a proximal action (MP flexion only): lasso and direct
      interosseous activation, or a distal action (MP flexion and IP extension). When
      Bouvier's maneuver is positive, a simple claw deformity may be treated by a
      passive procedure and/or an active palliative with proximal action procedure.
      This last procedure should be preferably indicated on index and middle finger if
      a few muscular motors are available. When claw deformity is complicated by MP
      stiffness in extension, a capsulectomy-capsuloplasty is indicated. When Bouvier's
      test is negative, and passive IP extension is possible, an active palliative with
      distal action procedure is indicated. Even when there is no claw deformity,
      intrinsic paralysis may be treated by an active palliative with proximal action
      procedure, in order to stabilize pinch and grasp. Capsuloplasties, lassos and
      interosseous activation procedures were all invented by Eduardo Zancolli.

PMID- 18325813
TI  - [Proliferating Brenner tumor: case report].
AB  - Brenner tumors account for only 1 to 2% of ovarian tumors. Proliferating Brenner
      tumors are characterized by an epithelial proliferation, resembling superficial
      well-differentiated urothelial carcinomas. A single 29-year-old patient was
      operated for an ovarian tumor. On gross examination, the tumor, which originated
      in the left ovary, was cystic multilocular and presented polyoid excrescences.
      Definitive histological exam showed a papillary proliferation lined by
      transitional cells without stroma infiltration. Mucinous cells lined some
      cavities. The diagnosis of proliferating Brenner tumor was made. Clinical and
      pathological characteristics of this rare entity will be discussed.

PMID- 18325814
TI  - Enhanced degradation of 2,4-dichlorophenol by ultrasound in a new Fenton like
      system (Fe/EDTA) at ambient circumstance.
AB  - This study investigated the effect of ultrasound (US) enhancement on the
      degradation of 2,4-DCP in a new Fenton like system. An obviously synergistic
      effect was observed after introduction of US into the Fe/EDTA system. Good
      correspondences with pseudo-first-order kinetic were found in each reaction
      system. It was demonstrated that the degradation rate constant (kobs) of DCP in
      US/Fe/EDTA was 7 and 32 times higher than those in Fe/EDTA and US system alone.
      Simultaneously, lower first-order kobs was also obtained in the investigation of
      decomposition of EDTA. At 60 min reaction time, Removals of 81% TOC, complete DCP
      and 89% EDTA were achieved. Low molecular weight organic acids are identified as
      the main products, which contribute to the solution self-buffer at about pH 6.5
      along with the reaction. In addition, the effect of initials condition, i.e.,
      iron addition, EDTA dosage, DCP concentration and US input power as well as
      reaction temperature were studied and reaction activation energy (Ea) was also
      calculated.

PMID- 18325815
TI  - Investigation on damage of DNA molecules under irradiation of low frequency
      ultrasound in the presence of hematoporphyrin-gallium (HP-Ga) complex.
AB  - The interaction of deoxyribonucleic acid (DNA) and hematoporphyrin-gallium (HP
      Ga) complex and the damage of DNA under ultrasonic irradiation in the presence of
      HP-Ga complex were studied by means of UV-vis spectrum, fluorescence spectrum and
      gelatin electrophoresis. In addition, some influence factors such as ultrasonic
      irradiation time, HP-Ga complex concentration, ionic strength and solution
      acidity on the damage of DNA were also considered. Under a certain condition, the
      damage degree of DNA was enhanced with increasing ultrasonic irradiation time, HP
      Ga complex concentration and ionic strength. Whether the pH value was too high or
      too low, it would be disadvantage to the damage of DNA. Perhaps, these results
      would be significant for driving sonodynamic treatment (SDT) to the clinic
      application in the future.

PMID- 18325816
TI  - Pure akinesia as initial presentation of PSP: a clinicopathological study.
AB  - Pure akinesia (PA) is a rare neurodegenerative condition that may represent a
      limited expression of progressive supranuclear palsy (PSP). Only a few
      pathological studies have been reported and its classification remains unclear.
      We report the case of a 57-year-old Caucasian man who was initially clinically
      diagnosed with classical PA. After four years the patient developed additional
      symptoms and signs compatible with the diagnosis of clinically probable PSP. The
      diagnosis of PSP was confirmed by post-mortem examination. Genetic analysis of
      the MAPT gene revealed an A0/A0 genotype, which has been repeatedly associated
      with the PSP phenotype, and might discriminate between PA and other gait
      disorders. Our case strengthens the hypothesis that PA should be considered as
      initial manifestation of PSP.

PMID- 18325817
TI  - Prevalence of Parkinson's disease and other types of parkinsonism in the Aeolian
      Archipelago, Sicily.
AB  - OBJECTIVE: To estimate prevalence of Parkinson's disease (PD) and other types of
      parkinsonism in the Aeolian Archipelago, Sicily. METHODS: We studied the
      frequency of PD and other types of parkinsonism in the Aeolian Archipelago
      (population 13,431). All potential cases were identified from available medical
      information sources. To ensure the completeness of the case-findings, a screening
      questionnaire was also mailed to residents aged 40 years and over. Subjects were
      considered prevalent if they fulfilled the SNES diagnostic criteria for PD, on
      prevalence day (January 1, 2001). RESULTS: We identified 17 patients with
      parkinsonism from medical sources, and 4 from mail-survey. Prevalence for all
      types of parkinsonism was 156.3/100,000 (95% CI 99.4-234.8). Fourteen subjects
      fulfilled diagnostic criteria for PD giving a crude prevalence of 104.2/100,000
      (95% CI 59.4-170.7) and 422.5/100,000 in the population aged 60 years and over.
      CONCLUSIONS: Prevalence of all types of parkinsonism and PD found in the Aeolian
      Archipelago is lower than that previously reported in Sicily.

PMID- 18325818
TI  - Biomarkers to detect central dopamine deficiency and distinguish Parkinson
      disease from multiple system atrophy.
AB  - OBJECTIVE: Biomarkers are increasingly important to diagnose and test treatments
      of neurodegenerative diseases such as Parkinson disease (PD). This study compared
      neuroimaging, neurochemical, and olfactory potential biomarkers to detect central
      dopamine (DA) deficiency and distinguish PD from multiple system atrophy (MSA).
      METHODS: In 77 PD, 57 MSA, and 87 control subjects, radioactivity concentrations
      in the putamen (PUT), caudate (CAU), occipital cortex (OCC), and substantia nigra
      (SN) were measured 2h after 6-[18F]fluorodopa injection, septal myocardial
      radioactivity measured 8min after 6-[18F]fluorodopamine injection, CSF and plasma
      catechols assayed, or olfaction tested (University of Pennsylvania Smell
      Identification Test (UPSIT)). Receiver operating characteristic curves were
      constructed, showing test sensitivities at given specificities. RESULTS: PUT:OCC,
      CAU:OCC, and SN:OCC ratios of 6-[18F]fluorodopa-derived radioactivity were
      similarly low in PD and MSA (p<0.0001, p<0.0001, p=0.003 compared to controls),
      as were CSF dihydroxyphenylacetic acid (DOPAC) and DOPA concentrations (p<0.0001,
      each). PUT:SN and PUT:CAU ratios were lower in PD than in MSA (p=0.004; p=0.005).
      CSF DOPAC correlated positively with PUT:OCC ratios (r=0.61, p<0.0001).
      Myocardial 6-[18F]fluorodopamine-derived radioactivity distinguished PD from MSA
      (83% sensitivity at 80% specificity, 100% sensitivity among patients with
      neurogenic orthostatic hypotension). Only PD patients were anosmic; only MSA
      patients had normal olfaction (61% sensitivity at 80% specificity). CONCLUSIONS:
      PD and MSA feature low PUT:OCC ratios of 6-[18F]fluorodopa-derived radioactivity
      and low CSF DOPAC and DOPA concentrations, cross-validating the neuroimaging and
      neurochemical approaches but not distinguishing the diseases. PUT:SN and PUT:CAU
      ratios of 6-[18F]fluorodopa-derived radioactivity, cardiac 6-[18F]fluorodopamine
      derived radioactivity, and olfactory testing separate PD from MSA.

PMID- 18325819
TI  - A case-based review of troubleshooting deep brain stimulator issues in movement
      and neuropsychiatric disorders.
AB  - OBJECTIVE: To review the spectrum of problems that can occur in the DBS patient
      and to suggest potential troubleshooting tips for identification and management
      of DBS related issues. BACKGROUND: Deep brain stimulation (DBS) has become
      commonplace for the treatment of medication-refractory neurological disorders.
      There remains no consensus on the best practices for screening, surgical
      techniques, and post-operative care. There are few experienced DBS programmers
      and scarce resources available describing approaches for troubleshooting DBS
      problems. METHODS: We present a case-based review that offers practical tips for
      the management and troubleshooting of difficult to manage DBS cases. We present
      10 cases to demonstrate common issues encountered in DBS management. RESULTS:
      There are many important difficulties that may be encountered with DBS devices,
      and practitioners should be aware of these potential problems, as well as
      rational management solutions. The following areas should be emphasized as
      potential causes of difficulties: a non-ideal initial DBS candidate, inadequate
      multidisciplinary team care, failure of perceived expectations, DBS procedural
      complication, hardware complication, suboptimal lead placement, programming,
      access to care, disease progression, and tolerance/habituation. CONCLUSION:
      Neurologists seeing DBS patients should become familiar with issues involved in
      difficult to manage DBS cases. Many "DBS failures" are currently treatable by
      appropriate medicine, programming, and surgical approaches.

PMID- 18325820
TI  - HFE gene mutations in a population of Italian Parkinson's disease patients.
AB  - An abnormal accumulation and distribution of brain iron are common to different
      neurodegenerative disorders, including Parkinson's disease (PD), and alteration
      of genes involved in iron metabolism cause neurodegeneration with brain iron
      accumulation. HFE participates in the regulation of iron metabolism, its
      mutations are primary cause of hereditary hemochromatosis and appear to be more
      frequent in neurodegenerative disorders such as Alzheimer's disease and
      amyotrophic lateral sclerosis. However, conflicting results were obtained in
      previous studies aimed to verify if nucleotide variations in HFE gene act as risk
      modifiers for PD. We used denaturing HPLC for scanning DNA sequence variations in
      exon 2 and 4 of HFE gene in a cohort of 475 Italian PD patients. We identified
      the most common H63D, C282Y and S65C, and also other 4 rare mutation types (R66H,
      R224W, E277K, and T281M). The allele frequency of H63D and C282Y was not
      statistically different from that of 2 control groups with similar mean age or of
      a large cohort of the same geographical area. In addition we could not find
      statistical differences in the clinical phenotypes of patients carrying at least
      one mutated HFE allele from those with the normal allele. We conclude that in the
      Italian population, the most common HFE mutations, H63D and C282Y are not
      associated with the individual risk to develop PD, nor have specific influence on
      the clinical features of the disease.

PMID- 18325821
TI  - Efficacy and safety of purified botulinum toxin type A (Dysport) for the
      treatment of benign essential blepharospasm: a randomized, placebo-controlled,
      phase II trial.
AB  - The majority of studies on the effects of botulinum toxin in blepharospasm
      patients have been small or unblinded. Our large-scale, multicenter, randomized
      clinical trial on the efficacy and safety of botulinum toxin (Dysport; 40, 80,
      and 120 units/eye) versus placebo in bilateral benign essential blepharospasm
      (BEB) supported the high efficacy and good safety profile of Dysport, with
      improvement in functional impairment, reduced frequency and intensity of facial
      spasms, and fewer withdrawals through lack of efficacy in the active treatment
      group compared with controls. The best balance of sustained efficacy and
      favorable safety profile was provided by 80 units of Dysport/eye in this study.

PMID- 18325822
TI  - Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's
      disease.
AB  - The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and
      exposure to environmental toxins contribute to specific neuronal loss in PD.
      Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has
      been proposed as a possible causative link between toxin exposure and PD
      neurodegeneration. In the present study BBB P-gp function was investigated in
      vivo in 10 early stage PD patients and 8 healthy control subjects using (R)
      [(11)C]-verapamil and PET. Cerebral volume of distribution (V(d)) of verapamil
      was used as measure of P-gp function. Both region of interest (ROI) analysis and
      voxel analysis using statistical parametric mapping (SPM) were performed to
      assess regional brain P-gp function. In addition, MDR1 genetic polymorphism was
      assessed. In the present study, a larger variation in V(d) of (R)-[(11)C]
      verapamil was seen in the PD group as compared to the control group. However,
      decreased BBB P-gp function in early stage PD patients could not be confirmed.

PMID- 18325823
TI  - Focal motor seizures mimicking hemifacial spasm.
AB  - A young female patient, who presented acutely with an unusual movement disorder
      characterized by hyperkinetic facial movements, was referred to us for hemifacial
      spasm. The only abnormality on neurological examination was myoclonus of the left
      perioral and bilateral periorbital muscles, exacerbated by mental tasks. A week
      later, the patient also presented two generalized tonic-clonic seizures on
      awakening and was successfully treated with antiepileptic drugs. Laboratory and
      neuroimaging investigations yielded normal findings. Although we were unable to
      identify a cortical generator, the concomitant occurrence of generalized
      seizures, the disappearance of symptoms after treatment and the topography of the
      myoclonus support an epileptic origin of this myoclonus.

PMID- 18325824
TI  - The endothelin axis in cancer.
AB  - The endothelin axis, comprising endothelins and their receptors, has recently
      emerged as relevant player in tumor growth and metastasis by regulating
      mitogenesis, cell survival, angiogenesis, bone remodeling, stimulation of
      nociceptor receptor, tumor-infiltrating immune cells, epithelial-to-mesenchymal
      transition, invasion and metastatic dissemination. Endothelin-1 participates in
      the growth and progression of a variety of tumors such as prostatic, ovarian,
      renal, pulmonary, colorectal, cervical, breast, bladder, endometrial carcinomas,
      Kaposi's sarcoma, brain tumors, melanoma, and bone metastases. This review
      highlights key signaling pathways activated by endothelin-1 axis in cancer, since
      the understanding the full spectrum activated by endothelin-1 is critical for the
      optimal design of targeted therapies. Preliminary experimental and clinical data
      demonstrate that interfering with endothelin receptor by using endothelin-1
      receptor antagonists alone and in combination with cytotoxic drugs or molecular
      inhibitors could represent a new mechanism-based antitumor strategy.

PMID- 18325825
TI  - An efficient locally affine framework for the smooth registration of anatomical
      structures.
AB  - Intra-subject and inter-subject nonlinear registration based on dense
      transformations requires the setting of many parameters, mainly for
      regularization. This task is a major issue, as the global quality of the
      registration will depend on it. Setting these parameters is, however, very hard,
      and they may have to be tuned for each patient when processing data acquired by
      different centers or using different protocols. Thus, we present in this article
      a method to introduce more coherence in the registration by using fewer degrees
      of freedom than with a dense registration. This is done by registering the images
      only on user-defined areas, using a set of affine transformations, which are
      optimized together in a very efficient manner. Our framework also ensures a
      smooth and coherent transformation thanks to a new regularization of the affine
      components. Finally, we ensure an invertible transformation thanks to the Log
      Euclidean polyaffine framework. This allows us to get a more robust and very
      efficient registration method, while obtaining good results as explained below.
      We performed a qualitative and quantitative evaluation of the obtained results on
      two applications: first on atlas-based brain segmentation, comparing our results
      with a dense registration algorithm. Then the second application for which our
      framework is particularly well suited concerns bone registration in the lower
      abdomen area. We obtain in this case a better positioning of the femoral heads
      than with a dense registration. For both applications, we show a significant
      improvement in computation time, which is crucial for clinical applications.

PMID- 18325826
TI  - Automatic segmentation of human brain sulci.
AB  - The neocortical surface has a rich and complex structure comprised of folds
      (gyri) and fissures (sulci). Sulci are important macroscopic landmarks for
      orientation on the cortex. A precise segmentation and labeling of sulci is
      helpful in human brain mapping studies relating brain anatomy and function. Due
      to their structural complexity and inter-subject variability, this is considered
      as a non-trivial task. An automatic algorithm is proposed to accurately segment
      neocortical sulci: vertices of a white/gray matter interface mesh are classified
      under a Bayesian framework as belonging to gyral and sulcal compartments using
      information about their geodesic depth and local curvature. Then, vertices are
      collected into sulcal regions by a watershed-like growing method. Experimental
      results demonstrate that the method is accurate and robust.

PMID- 18325827
TI  - Is there a serious risk of resistance development to azoles among fungi due to
      the widespread use and long-term application of azole antifungals in medicine?
AB  - It is well known that development of antibiotic resistance in bacteria is not a
      matter of if but of when. Recently, azoles have been recommended for long-term
      prophylaxis of invasive fungal infections; hence, it could be argued that fungi
      also will become resistant to these agents. However, fungi are different from
      bacteria in several critical points. Bacteria display several resistance
      mechanisms: alteration of the target, limited access to the target and
      modification/inactivation of the antibacterial compound. In fungi some mechanisms
      of resistance to azoles are also known; with azoles for example, alterations of
      the 14alpha-demethylase target, as well as efflux pumps. It has been observed
      that these phenotypes develop in yeast populations either due to mutations or to
      selection processes. However, enzymes which destroy azoles are not found.
      Furthermore, a horizontal transfer of genes coding resistance traits does not
      occur in fungi, which means that an explosive expansion of resistances is
      unlikely to occur, especially in moulds. Indeed, in epidemiologic studies on
      human and environmental isolates there is convincing evidence that azole
      resistance is quite uncommon.

PMID- 18325828
TI  - Quantitative genetics in the age of omics.
AB  - The use of natural variation in the genetic dissection of quantitative traits has
      a long-standing tradition. Recent advances in high-throughput technologies for
      the quantification of biological molecules have shifted the focus in quantitative
      genetics from single traits to comprehensive large-scale analyses. So-called omic
      technologies now enable geneticists to take a look in the black box that
      translates genetic information into biological function. These processes include
      transcriptional and (post) translational regulation as well as metabolic
      signaling pathways. The progress made in analytical and statistical techniques
      now allows the construction of regulatory networks that integrate the different
      levels of the biological information flow from gene-to-function.

PMID- 18325829
TI  - Synthesis of Eu(III) and Tb(III) complexes with novel pyridine dicarboxamide
      derivatives and their luminescence properties.
AB  - A novel ligand, N2,N6-bis[2-(3-methylpyridyl)]pyridine-2,6-dicarboxamide (L2) and
      the corresponding Eu(III) and Tb(III) hydrochlorate complexes have been
      synthesized and characterized in detail based on elemental analysis, IR and NMR.
      The crystal and molecular structure of the complexes was determined by X-ray
      crystallography. The Eu(III) and Tb(III) ions were found to coordinate to the
      amido nitrogen atoms and pyridine nitrogen atoms. The luminescence properties of
      lanthanide complexes in solid state, in different solutions and in different pH
      value were investigated. The result shows that Tb(III) complexes exhibit more
      efficient luminescence than Eu(III) complexes, and the ligand (L2) is an
      excellent sensitizer to Tb(III) ion.

PMID- 18325830
TI  - Vibrational spectrum, ab initio calculations, conformational stabilities and
      assignment of fundamentals of the Ci conformer of 1,4-dichlorobutane.
AB  - The infrared and Raman spectrum of 1,4-dichlorobutane is reported in solid,
      liquid and gas. Ab initio calculations for the nine stable or metastable
      conformers of 1,4-dichlorobutane are reported for Moller-Ploessett second order
      electron correlation and B3LYP density functionals with a variety of basis sets,
      using approximations as high as 6-311+g(2d, 2p). Normal coordinate calculations
      were conducted for the nine conformers and the results used to provide
      assignments for some of the observed infrared and Raman bands. An attempt to use
      the assignments together with the ab initio intensities or Raman activities to
      investigate the composition of the liquid at room temperature proved modestly
      successful, and suggested that the populations are altered from those expected in
      the gas phase by interactions of the permanent electric dipole moments with the
      dipolar plasma in which the conformers are immersed in the liquid. A substantial
      disagreement between the Moeller-Ploessett and density functional results is
      reported, and the calculation of intensities and activities is insufficiently
      accurate to allow detailed interpretation of the spectrum of the room temperature
      liquid. A complete assignment of fundamentals is given for the conformer of Ci
      symmetry, and one Raman and one infrared band is identified with the C2h
      conformer. All the other infrared and Raman bands in the liquid or the gas are
      composites of several contributors.

PMID- 18325831
TI  - A near-infrared spectroscopic study of the phosphate mineral pyromorphite
      Pb5(PO4)3Cl.
AB  - Spectral properties as a function composition are analysed for a series of
      selected pyromorphite minerals of Australian origin. The minerals are
      characterised by d-d transitions in NIR from 12,000 to 8000 cm(-1) (0.83-1.25
      microm). A broad signal observed at approximately 10,000cm(-1) (1.00 microm) is
      the result of ferrous ion impurity in pyromorphites and follows a relationship
      between band intensity in the near-infrared spectra and ferrous ion
      concentration. The iron impurity causes a change in colour from green-yellow to
      brown in the pyromorphite samples. The observation of overtones of the OH(-)
      fundamentals, confirms the presence OH(-) in the mineral structure. The
      contribution of water-OH overtones in the NIR at 5100 cm(-1) (1.96 microm) is an
      indication of bonded water in the minerals of pyromorphite. Spectra in the mid-IR
      show that pyromorphite is a known mixed phosphate and arsenate complex,
      Pb5(PO4,AsO4)3Cl. A series of bands are resolved in the infrared spectrum of
      pyromorphite at 1017, 961 and 894 cm(-1). The first two bands are assigned to
      nu(3), the antisymmetric stretching mode and the third band at 894 cm(-1) is the
      symmetric mode of the phosphate ion. Similar patterns are shown by other
      pyromorphite samples with variation in intensity. The cause of multiple bands
      near 800 cm(-1) is the result of isomorphic substitution of (PO4)(3-) by (AsO4)(3
      ) and the spectral pattern relates to the chemical variability in pyromorphite.
      The presence of (AsO4)(3-) is significant in certain pyromorphite samples.

PMID- 18325832
TI  - Clinical and genetic characterization of severe influenza B-associated diseases
      during an outbreak in Taiwan.
AB  - BACKGROUND: Mismatches between circulating and vaccine strains of influenza virus
      had been observed in Taiwan. A comprehensive clinical and genetic analysis of
      influenza B viruses-associated important diseases was lacking. OBJECTIVES:
      Clinical and phylogenetic analysis of influenza B viruses during an outbreak in
      Taiwan. STUDY DESIGNS: Clinical manifestations of hospitalized, culture-confirmed
      patients were analyzed from July 2004 to June 2005. Partial genome sequence
      analysis of hemagglutinin (HA), neuraminidase (NA), and nonstructural (NS) genes
      were performed in 54 influenza B isolates during the study period, and nine
      srandomly chosen isolates during 2000 and 2003. RESULTS: Three specific diseases
      were found in these patients, including 13 of encephalitis/encephalopathy, 28 of
      influenza-associated myositis (IAM), and one of acute respiratory distress
      syndrome (ARDS). Three phylogenetic groups were identified, including reassortant
      strains-group 1 (Victoria lineage of HA, Yamagata lineage of NA, clade A of NS),
      group 2 (Yamagata lineage of HA, Yamagata lineage of NA, clade A of NS), and
      group 3 (Yamagata lineage of HA, Yamagata lineage of NA, clade B of NS).
      CONCLUSIONS: Severe influenza B-associated disease in children was not rare and
      might be fatal. We offered the evidence of co-circulation of the two HA lineages
      in the same outbreak.

PMID- 18325833
TI  - Comparative morphology and molecular phylogeny of Apicoporus n. Gen.: a new genus
      of marine benthic dinoflagellates formerly classified within Amphidinium.
AB  - The composition of the dinoflagellate genus Amphidinium is currently polyphyletic
      and includes several species in need of re-evaluation using modern morphological
      and phylogenetic methods. We investigated a broad range of uncultured morphotypes
      extracted from marine sediments in the Eastern Pacific Ocean that were similar in
      morphology to Amphidinium glabrum Hoppenrath and Okolodkov. To determine the
      number of distinct species associated with this phenotypic diversity, we
      collected LM, SEM, TEM and small subunit ribosomal DNA sequence information from
      different morphotypes, including the previously described A. glabrum. Both
      comparative morphological and molecular phylogenetic data supported the
      establishment of a new genus, Apicoporus n. gen., including at least two species,
      A. glaber n. comb., and A. parvidiaboli n. sp. Apicoporus is characterized by
      having amphiesmal pores and an apical pore covered by a hook-like protrusion;
      neither of these characters has been observed in other athecate dinoflagellates.
      The posterior end of Apicoporus parvidiaboli possessed varying degrees of "horn
      formation", ranging from slight to prominent. By contrast, the posterior end of
      Apicoporus glaber was distinctively rounded and lacked evidence of horn
      formation. Although these species were previously interpreted to be obligate
      heterotrophs, TEM and epifluorescence microscopy demonstrated that some cells of
      both species had unusually small but otherwise typical dinoflagellate plastids.
      The number and density of plastids in any particular cell varied significantly in
      the genus, but the plastids were almost always concentrated at the posterior end
      of the cells or around the nucleus. The presence of cryptic photosynthetic
      plastids in these benthic species suggests that photosynthesis might be much more
      widespread in dinoflagellates than is currently assumed.

PMID- 18325835
TI  - Emergence and spread of antibiotic-resistant Gram-positive bacterial pathogens.
AB  - Development of multiple resistances to antibiotics in staphylococci, enterococci
      and pneumococci became a health threat during the past 20 years, not only with
      respect to nosocomial infections. This resistance development is based on
      acquisition of resistance genes by predominant epidemic subpopulations (clonal
      complexes). Although emergence and spread of methicillin-resistant Staphylococcus
      aureus is associated with a limited number of epidemic clones which have been
      widely disseminated, acquisition of SCCmec elements by susceptible ancestors has
      taken place at different times and at different locations. Among Staphylococcus
      epidermidis and Enterococcus faecium, one clonal complex, which had acquired
      resistance genes at several occasions, is widely disseminated in hospitals. Also
      in Streptococcus pneumoniae, antibiotic resistance is preferentially associated
      with clonal lineages which have a capacity for spreading. They became, however,
      more rare after introduction of the 7-valent conjugate vaccine.

PMID- 18325837
TI  - Les liaisons dangereuses: immunological synapse formation in animals and plants.
AB  - The immunological synapse in vertebrates describes a specialized junction between
      a T cell and a target cell, enabling execution of immune responses through focal
      secretion. Recent insights in the plant immune system suggest that plant cells
      assemble a pathogen-inducible machinery at the cell surface that shares several
      features with the immunological synapse. Apparent mechanistic commonalities
      include co-stimulatory non-self alarm signals as triggers, cell polarization
      driven by actin cytoskeleton remodeling, protein concentration into ring-shaped
      assemblies at the cell periphery and focal exocytosis mediated by soluble N
      ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins that
      are core factors for vesicle fusion. Although in plants, execution of immune
      responses by polar secretion seems to be a cell type-independent property, its
      confinement to T cells in the vertebrate immune system might reflect a greater
      division of labor.

PMID- 18325839
TI  - Endoscopic management of uterine fibroids.
AB  - Uterine fibroids are the most common benign tumours of the uterus. Management
      depends on the symptoms, location and size of the fibroids, and the patient's
      desire to conceive. Surgical management of uterine fibroids has changed from
      laparotomy to minimally invasive surgery. Uterine fibroids are usually
      asymptomatic and do not require treatment. Laparoscopic myomectomy is the best
      treatment option for symptomatic women with uterine fibroids who wish to maintain
      their fertility. The authors' criteria for laparoscopic myomectomy are a fibroid
      of <15 cm in size, and no more than three fibroids with a size of 5 cm. Compared
      with laparotomy, laparoscopic myomectomy has the advantages of small incisions,
      short hospital stay, less postoperative pain, rapid recovery and good assessment
      of other abdominal organs. Due to the concern of decreased ovarian reserve,
      uterine artery embolization is not advisable for these women. In addition, it is
      associated with high risks of miscarriages, preterm delivery and postpartum
      bleeding. Laparoscopic myolysis causes severe adhesion formation. Women with
      submucous fibroids receive myomectomy by hysteroscopy. For women who have
      completed their family, laparoscopic hysterectomy could be performed. Most
      fibroids can be managed endoscopically either by laparoscopy or hysteroscopy.
      Surgeon expertise, especially laparoscopic suturing, is crucial. Laparoscopic
      myomectomy is still the best treatment option for symptomatic women with uterine
      fibroids who wish to maintain their fertility. Hysteroscopic myomectomy is an
      established surgical procedure for women with excessive uterine bleeding,
      infertility or repeated miscarriages.

PMID- 18325838
TI  - Accelerated atherosclerosis in ApoE deficient lupus mouse models.
AB  - The accelerated development of atherosclerosis with increased risk of
      cardiovascular disease in systemic lupus erythematosus (SLE) patients is not well
      understood. An appropriate mouse model would greatly help to understand the
      mechanisms of this association. We have therefore combined the ApoE(-/-) model of
      atherosclerosis with three different murine models of SLE. We found that
      induction of cGVH in B6.ApoE(-/-) mice, breeding a Fas null gene onto the
      B6.ApoE(-/-) mice, and breeding the ApoE(-/-) defect onto MRL/lpr mice all caused
      a modest increase of atherosclerosis at 24 weeks of age compared to B6.ApoE(-/-)
      controls. B cells in B6.ApoE(-/-) mice had certain phenotypic differences
      compared to congenic C57BL/6 mice, as indicated by high expression of MHC II,
      Fas, CD86, and by increased number of cells bearing marginal zone phenotype.
      Furthermore, B6ApoE(-/-) mice had significant titers of anti-oxLDL and anti
      cardiolipin autoantibodies compared to their B6 counterparts. Our studies also
      indicate that, following induction of cGVH, marginal zone B cells in B6.ApoE(-/-)
      are depleted, and there is considerable increase in anti-oxLDL and anti
      cardiolipin abs along with secretion of lupus-specific autoantibodies, such as
      anti-dsDNA and anti-chromatin abs. Histological sections showed that cGVH and/or
      Fas deficiency could exacerbate atherosclerosis. The production of anti-oxLDL and
      anti-cardiolipin in ApoE(-/-) mice was also increased. These observations define
      a connection between induction of lupus-like symptoms and development of severe
      atherosclerosis in ApoE deficient lupus mouse models.

PMID- 18325841
TI  - Self-proteolysis regulation in the Bothrops jararaca venom: the metallopeptidases
      and their intrinsic peptidic inhibitor.
AB  - Snake venom proteome variation is a well-documented phenomenon, whereas peptidome
      variation is still relatively unknown. We used a biological approach to explore
      the inhibitory activities present in the whole venom of Bothrops jararaca that
      prevents the venom self-proteolysis and/or digestion of the glandular tissue.
      Although snake venom metallopeptidases have long been known from the biochemical
      up to the clinical point of view, the mechanisms by which these enzymes are
      regulated in the reptile's venom gland remain fairly unknown. We have
      successfully demonstrated that there are three synergistic weak inhibitory
      mechanisms that are present in the crude venom that are able to abolish the
      metallopeptidase activity in situ, namely: (i) citrate calcium chelation; (ii)
      acidic pH and; (iii) enzymatic competitive inhibition by the tripeptide
      Pyroglutamyl-lysyl-tryptophan. Taken together, these three factors become a
      strong set-up that inhibits the crude venom metallopeptidase activity as well as
      a purified metallopeptidase from this same venom. However, this inhibition can be
      totally reverted by dilution into an optimal pH solution, such as the blood.

PMID- 18325842
TI  - Diadenosine polyphosphates are selective vasoconstrictors in human coronary
      artery bypass grafts.
AB  - Diadenosine polyphosphates (Ap(n)A) are released by degranulating platelets and
      high, local concentrations may form at sites of platelet activation. Radial
      artery grafts, now often used alongside the internal mammary artery in coronary
      artery bypass surgery, are particularly reactive to several vasoconstrictors but
      the response to Ap(n)A has not been investigated. This study compared the
      vasoconstrictor activity of Ap(n)A in human radial artery with other vessels
      commonly used as bypass grafts. Radial artery demonstrated robust concentration
      dependent vasoconstriction to Ap(n)A (n=4-6) at concentrations in the micromolar
      range. In contrast, average responses in internal mammary artery were negligible.
      Cross-desensitization revealed that Ap(n)A-mediated vasoconstriction occurred via
      an alphabetamethyleneATP-sensitive receptor. Responses to both Ap(5)A and
      alphabetamethyleneATP were inhibited by suramin but were insensitive to the
      P2X(1) receptor antagonist 8,8'-[Carbonylbis(imino-4,1-phenylenecarbonylimino-4,1
      phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid (NF279).
      Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) enhanced responses
      to Ap(5)A. Similar responses were obtained in saphenous vein. In conclusion,
      diadenosine polyphosphates contract radial artery and saphenous vein by an as yet
      uncharacterized P2X receptor but have only limited activity in internal mammary
      artery. The selective activity of diadenosine polyphosphates in radial artery
      would implicate them as potential mediators of post-operative contraction in this
      graft.

PMID- 18325843
TI  - Clinical impact of capsule endoscopy on management of gastrointestinal disorders.
AB  - BACKGROUND & AIMS: The impact of capsule endoscopy (CE) findings on patient
      management is unknown. We assessed the impact of CE findings on patient
      management, and whether physicians use these to alter management plans. METHODS:
      Physicians requesting CE were contacted before the examination and asked what
      their management recommendations would be if CE were not available. These
      responses were compared with management recommendations by the same requesting
      physician after the CE. The responses were recorded on a data form. The
      physicians reading the CE were blinded to the pre-CE responses. The end points
      assessed were change in overall management and specific change in diagnostic and
      treatment strategy. RESULTS: Responses were obtained from physicians before and
      after CE in 98 patients. Requesting physicians (n = 40) were composed of
      gastroenterologists (92%), internists (3%), and other specialties (5%).
      Physicians changed post-CE overall management plans in 67% of patients. Of these
      physicians, 74% did so as a result of CE findings (P = .001). Specifically,
      physicians changed post-CE diagnostic strategy in 61% of patients; the diagnostic
      strategy was changed to less complex or decreased risk associated in 43% of
      patients. Of those requesting physicians who changed their diagnostic strategy,
      75% did so as a result of CE (P = .004). When treatment strategy was evaluated
      before and after CE, there was a change in 31% of patients. CONCLUSIONS:
      Physicians requesting CE alter management in the majority of patients on the
      basis of CE findings. Diagnostic strategy is changed in the majority of patients,
      and often a less complex approach is pursued.

PMID- 18325844
TI  - Agenesis of the gallbladder.

PMID- 18325845
TI  - Novel ablative approach for atrial fibrillation to decrease risk of esophageal
      injury.

PMID- 18325846
TI  - Atypical atrial flutter.

PMID- 18325847
TI  - Cardiac image registration of the left atrium and pulmonary veins.
AB  - Cardiac image registration, in the context of the left atrium, is intermodal,
      with the acquired image and the real-time reference image residing in different
      image spaces, and involves optimization, where one image space is transformed
      into the other. Geometry-based methods, which include using fiducial points
      and/or surface-based techniques, are usually used for cardiac image registration.
      During fiducial point registration, fiducial points are either external skin
      markers or manually determined by marking anatomical landmarks using mapping
      catheters. Usually, a minimum of three noncollinear points is needed for optimal
      registration. During surface registration, each of the images' surfaces are
      characterized to determine the best transformation between them. Unlike the rigid
      body registration used extensively in the study of the brain, cardiac image
      registration is unique and challenging. In addition to the errors inherent in
      intermodal registration, errors due to respiration and cardiac motion during the
      cardiac cycle are specific to cardiac image registration. This review addresses
      the basic principles of registration and the inherent registration errors as they
      relate to cardiac imaging and registration.

PMID- 18325848
TI  - Image integration for catheter ablation: searching for the perfect match.

PMID- 18325849
TI  - Large, single-center, single-operator experience with transvenous lead
      extraction: outcomes and changing indications.
AB  - BACKGROUND: Lead extraction is increasingly necessary given the exponential
      growth in cardiac device implantation. Meanwhile, the tools, indications, and
      outcomes of this procedure continue to change. OBJECTIVE: The purpose of this
      study was to examine contemporary indications, outcomes, and complications of
      transvenous lead extraction in a large series of patients at a high-volume lead
      extraction center. METHODS: We performed a retrospective cohort study of
      consecutive patients undergoing lead extraction at a single, high-volume center.
      Patient and lead characteristics and the indications, outcomes, and need for
      laser assistance were analyzed. RESULTS: From January 2000 to March 2007, a total
      of 975 chronic endovascular leads were removed from 498 patients. Median implant
      duration was 5.7 years (range 0.5-32.7 years). Indications were infection
      (60.3%), mechanical lead failure (29.3%), and upgrade of device system (8.8%).
      Over the study period, lead malfunction decreased relative to other indications.
      Laser assistance for extraction was more likely with leads implanted longer than
      3.4 years compared to less than 3.4 years (odds ratio 6.15, 95% confidence
      interval 3.35-11.28) and with implantable cardioverter-defibrillator leads
      compared to pacemaker leads (odds ratio 3.44, 95% confidence interval 1.84-6.43).
      Overall, 97.5% of the leads were completely removed. Major complications occurred
      in 2 (0.4%) patients. Only one patient required cardiac surgery. No deaths
      occurred. CONCLUSION: In a high-volume center, lead extraction has a high success
      rate and low complication rate. Infection was the most common indication overall.
      Lead failure has decreased in relative proportion. Implantable cardioverter
      defibrillator leads and longer lead implant time are associated with a
      requirement for laser lead extraction.

PMID- 18325850
TI  - Clinical predictors and relationship between early and late atrial
      tachyarrhythmias after pulmonary vein antrum isolation.
AB  - BACKGROUND: Several studies have reported early (EAT) and late (LAT) atrial
      tachyarrhythmias following atrial fibrillation (AF) ablation, but the factors
      associated with them and their clinical significance are not well known.
      OBJECTIVE: The purpose of this study was to investigate the predictors and the
      relationship between EAT and LAT after AF ablation. METHODS: A total of 1298
      patients with paroxysmal (54%), persistent (18%), or permanent (28%) AF underwent
      intracardiac echocardiography-guided pulmonary vein antrum isolation and were
      followed for 41 +/- 10 months. EAT and LAT were defined as an episode of AF or
      atrial flutter/tachycardia lasting longer than 1 minute that occurred within the
      first 3 months of ablation and after 3 months postablation, respectively.
      RESULTS: After a single ablation procedure, EAT developed in 514 (40%) patients
      and LAT in 292 (22%) patients. At a multivariable analysis, longer AF duration
      (odds ratio [OR] 1.03), history of hypertension (OR 1.32), left atrial
      enlargement (OR 1.55), permanent AF (OR 1.72), and lack of superior vena cava
      isolation (OR 1.60) were significantly associated with EAT. Independent
      predictors of LAT were longer AF duration (OR 1.03), history of hypertension (OR
      1.65), persistent (OR 2.17) or permanent AF (OR 2.28), and occurrence of EAT (OR
      30.62). The risk of LAT was inversely related to the time to first EAT occurrence
      (OR 20, 54, and 1,052 in first, second, and third month, respectively). Notably,
      49% of patients with EAT did not experience LAT. CONCLUSION: EAT strongly predict
      LAT. However, EAT did not automatically mean ablation failure. Delaying redo
      procedure may be appropriate during the first 2 months after ablation. Longer AF
      duration, hypertension, and nonparoxysmal AF are independent predictors of EAT
      and LAT.

PMID- 18325851
TI  - Noninvasive electrocardiographic imaging (ECGI) of a univentricular heart with
      Wolff-Parkinson-White syndrome.

PMID- 18325852
TI  - Real-time representation of multielectrode ablation catheters by integration of
      computed tomographic geometry with three-dimensional electroanatomic mapping of
      left atrium and pulmonary veins.

PMID- 18325854
TI  - The Ku-dependent non-homologous end-joining but not other repair pathway is
      inhibited by high linear energy transfer ionizing radiation.
AB  - Ionizing radiation (IR) induced DNA double strand breaks (DSBs) are repaired by
      both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR)
      in mammalian cells. The NHEJ repair includes a Ku-dependent main pathway and a
      PARP-1-dependent complementary pathway. Compared with low linear energy transfer
      (LET) IR (X or gamma ray) at the same doses, high LET IR (high-charge particles)
      induces more cell death because of ineffective DNA repair. However, it remains
      unclear whether high LET IR inhibits all repair or specifically one repair
      pathway. By combining the assays of clonogenic survival, G2M checkpoint and
      gammaH2AX in the cell lines with deficiencies in different repair genes, we show
      here that high LET IR inhibits only the Ku-dependent main NHEJ pathway and does
      not inhibit either the HRR pathway or the PARP-1-dependent complementary NHEJ
      pathway. In addition, by developing an assay to detect small fragments of DSB
      (<400 bp) and by detecting the binding abilities of purified Ku and PARP to
      different sized dsDNA, we present a possible link for explaining the phenotypes.
      When compared with low LET IR at the same dose, high LET IR might induce similar
      yields of DNA DSBs in total but it might induce more small fragments of DNA DSBs
      (<40 base pairs) that prevent Ku binding efficiently to two ends of one DSB
      fragment at the same time, thus delaying Ku-dependent repair.

PMID- 18325853
TI  - Evaluating a two-step approach to sexual risk reduction in a publicly-funded STI
      clinic: rationale, design, and baseline data from the Health Improvement Project
      Rochester (HIP-R).
AB  - BACKGROUND: Sexually transmitted infection (STI) clinics provide an opportune
      setting for HIV prevention efforts. This randomized controlled trial evaluated a
      unique, two-step approach to sexual risk reduction at a publicly-funded STI
      clinic. METHODS: During an initial visit, patients completed an audio-computer
      assisted self-interview (ACASI), were randomized to and received one of two brief
      interventions, obtained medical care, and completed a post-assessment. Next, two
      thirds of the patients were assigned to attend an intensive sexual risk reduction
      workshop. At 3, 6, and 12 months, patients completed additional ACASIs and
      provided urine specimens to assess behavior change and incident STIs. RESULTS:
      During a 28-month interval, 5613 patients were screened, 2691 were eligible, and
      1483 consented to participate and were randomized; the modal reason for declining
      was lack of time (82%). Consenting patients included 688 women and 795 men; 64%
      of participants were African-American. The sample was low-income, with 57%
      reporting an annual income of less than $15,000; most participants (62%) had a
      high school education or less, and 51% were unemployed. Sexual risk behavior was
      common, as indicated by multiple sexual partners (mean=32.8, lifetime; mean=2.8,
      past 3 months), unprotected sex (mean=17.3 episodes, past 3 months), and prior
      STIs (mean=3.3, lifetime; 23% at baseline). Bivariate analyses confirmed our
      prediction that HIV-related motivation and behavioral skills would be related to
      current sexual risk behavior. All patients received a brief intervention; patient
      satisfaction ratings were uniformly high for both interventions (all means
      >or=3.7 on 4-point scales). Fifty-six percent of invited patients attended the
      intensive workshop, and attendance did not differ as a function of brief
      intervention. Patient satisfaction ratings were also uniformly positive for the
      workshop interventions (all means >or=3.6). Return to follow-up assessments
      exceeded 70%. CONCLUSIONS: Results demonstrate that implementing an HIV
      preventive program in a busy, public clinic is feasible and well-accepted by
      patients. Ongoing evaluation will determine if the interventions reduce sexual
      risk behavior and lower incident STIs.

PMID- 18325855
TI  - Quantitative 2-D gel electrophoresis-based expression proteomics of albumin and
      IgG immunodepleted plasma.
AB  - Proteomic analysis of plasma is challenging because of its large dynamic range,
      which prevents the detection of low abundance proteins. Immunodepletion of high
      abundance proteins, such as albumin and IgG, has emerged as a favored technology
      to overcome this problem; however its suitability in quantitative expression
      proteomics has not yet been adequately addressed. In this study, albumin and IgG
      immunodepletion was evaluated by ELISAs and the reproducibility of depletion was
      tested with 2-DGE. Depletion of plasma resulted in removal of 62+/-1.2% of the
      total protein, 93+/-1.4% of the albumin (0.43 microg/microL, residual), and 94+/
      1.5% of the IgG (0.21 microg/microL, residual). These results were confirmed by
      immunoblotting. Computerized image analysis of 2-D gels using Progenesis
      SameSpots software revealed an enhancement in the number of visible spots (675
      1325), with 10+/-6% inter-gel variability in spot density. LC-ESI-MS/MS
      identification of newly resolved protein spots further validated the procedure.
      An innovative application of the software employed led to identification of 11
      proteins lost non-specifically during depletion. This study demonstrates the
      effectiveness of immunodepletion of albumin and IgG in quantitative 2-DGE-based
      differential analysis of plasma proteins.

PMID- 18325856
TI  - Development and validation of a quantitative assay for the measurement of
      miltefosine in human plasma by liquid chromatography-tandem mass spectrometry.
AB  - A sensitive and specific liquid chromatography-tandem mass spectrometry (LC
      MS/MS) assay for the quantification of miltefosine is presented. A 250 microL
      human EDTA plasma aliquot was spiked with miltefosine and extracted by a solid
      phase extraction method. Separation was performed on a Gemini C18 column (150 mm
      x 2.0 mm I.D., 5 microm) using an alkaline eluent. Detection was performed by
      positive ion electrospray ionization followed by triple-quadrupole mass
      spectrometry. The assay has been validated for miltefosine from 4 to 2000 ng/mL
      using 250 microL human EDTA plasma samples. Results from the validation
      demonstrate that miltefosine can be accurately and precisely quantified in human
      plasma. At the lowest level, the intra-assay precision was lower than 10.7%, the
      inter-assay precision was 10.6% and accuracies were between 95.1 and 109%. This
      assay is successfully used in a clinical pharmacokinetic study with miltefosine.

PMID- 18325857
TI  - Quantification of seven nucleoside/nucleotide reverse transcriptase inhibitors in
      human plasma by high-performance liquid chromatography with tandem mass
      spectrometry.
AB  - A simple analytical method was developed in 100 microL of plasma for the
      simultaneous assay of the 7 nucleoside/nucleotide reverse transcriptase
      inhibitors (abacavir, didanosine, emtricitabine, lamivudine, stavudine,
      tenofovir, and zidovudine) currently used for the treatment of HIV-infected
      patients. After adding the internal standard, 6-beta-hydroxy-theophyline, plasma
      samples were precipitated with 500 microL acetonitrile and the supernatants were
      evaporated to dryness. The residues were reconstituted with 500 microL of water
      and 10 microL of the extracts were injected in the chromatographic system. The
      chromatographic separation was performed with a C-18 column and a gradient mobile
      phase consisting of a mixture of water and acetonitrile, both containing 0.05%
      formic acid. Analytes quantification was performed by electrospray ionisation
      triple quadrupole mass-spectrometry in the positive mode using selected reaction
      monitoring (SRM). Intra- and inter-assay precision and accuracy were lower than
      20% for the limit of quantification, and 15% for higher concentrations. The
      method has been implemented to assess plasma concentrations of patients infected
      by HIV and was found suitable for therapeutic drug monitoring.

PMID- 18325858
TI  - Randomized controlled experiments in health and social sciences: some conceptual
      issues.
AB  - This brief article outlines some difficulties as well as benefits in conducting
      randomized controlled trials in social science settings especially in developing
      countries. Some of the historical developments are summarized and certain
      applications in health sciences are discussed from methodological and policy
      standpoints.

PMID- 18325859
TI  - Treating body dysmorphic disorder with medication: evidence, misconceptions, and
      a suggested approach.
AB  - Body dysmorphic disorder (BDD) is a relatively common and often disabling
      disorder with high morbidity and mortality. Both psychotropic medication and
      cognitive behavioral therapy (CBT) are considered first-line treatments for BDD,
      and medication treatment is often essential for more severely ill and suicidal
      patients. In this practical overview of the pharmacotherapy of BDD, we briefly
      describe BDD's clinical features, associated morbidity, and how to recognize and
      diagnose BDD. We describe the importance of forming a therapeutic alliance with
      the patient, the need for psychoeducation, and other essential groundwork for
      successful treatment of BDD. We review available pharmacotherapy research, with a
      focus on serotonin-reuptake inhibitors (SSRIs, or SRIs), which are currently
      considered the medication of choice for BDD. Many patients have substantial
      improvement in core BDD symptoms, psychosocial functioning, quality of life,
      suicidality, and other aspects of BDD when treated with appropriate
      pharmacotherapy that targets BDD symptoms. We also discuss practical issues such
      as dosing, length of treatment, and potential side effects associated with the
      use of SRIs. In addition, we discuss pharmacotherapy approaches that can be tried
      if SRI treatment alone is not adequately helpful. Finally, some misconceptions
      about pharmacotherapy, gaps in knowledge about BDD's treatment, and the need for
      additional research are discussed.

PMID- 18325860
TI  - Constitutive modeling of the stress-strain behavior of F-actin filament networks.
AB  - The central role of the cytoskeleton in both healthy and diseased cellular
      functions makes it a compelling subject for detailed three-dimensional (3D)
      micromechanical modeling. Microstructural features of the cytoskeleton govern the
      cell's mechanical behavior in many of the regulating cellular functions including
      cell division, adhesion, spreading, migration, contraction, and other
      mechanotransductive effects which influence biochemical processes. Actin
      microfilaments (AF) combine to form one of the predominant cytoskeletal networks
      important to these biological processes. Here, the AF cytoskeletal microstructure
      and stress-strain behavior is modeled via a microstructurally-informed continuum
      mechanics approach. The force-extension behavior of the individual filaments is
      captured using the MacKintosh derivation of the worm-like chain (WLC)
      constitutive relationship for short chains where a new and direct analytical
      expression for the filament force as a function of filament extension is
      developed in this paper. The filament force-extension behavior is then used in
      conjunction with the Arruda-Boyce eight-chain network model to capture the 3D
      multiaxial stress-strain behavior of the network. The resulting 3D cytoskeletal
      network constitutive model provides the ability to track microstructural stretch
      and orientation states during 3D macroscopic stretching conditions. The non
      affine nature of the network model effectively accommodates the imposed
      macroscopic shear strain through filament rotation and a relatively small amount
      of filament stretch. These characteristics enable the network model, using
      physically realistic material properties, to capture the initial stiffness of the
      AF network as well as the nonlinear strain stiffening observed at large stresses.
      The network model predictions compare favorably with published microrheological
      data of in vitro AF networks.

PMID- 18325861
TI  - Topography and biocompatibility of patterned hydrophobic/hydrophilic zein layers.
AB  - The topography and biocompatibility of zein layers adsorbed on patterned
      templates containing hydrophilic and hydrophobic regions were investigated.
      Nanopatterned templates consisting of hydrophilic lines on a hydrophobic
      background were drawn by dip-pen nanolithography (DPN) on gold-coated surfaces.
      16-Mercaptohexadecanoic acid (COOH(CH(2))(15)SH, MHA) was used as primary ink to
      generate hydrophilic lines. Unpatterned surfaces were backfilled with 18
      octadecanethiol (CH(3)(CH(2))(17)SH, ODT), which generated hydrophobic regions.
      Zein was allowed to adsorb on patterned surfaces from alcohol-water solutions.
      The topography of zein deposits was observed by atomic force microscopy (AFM).
      Height profiles from AFM measurements revealed that zein deposits followed
      closely the nanopatterned templates. The biocompatibility of zein layers
      assembled over hydrophilic/hydrophobic micropatterned templates was investigated.
      Templates containing MHA lines and ODT regions were generated by micro-contact
      printing (microCP). Mouse fibroblasts seeded on patterned zein layers
      proliferated on zein deposited over MHA lines, but not on zein over ODT. The
      experiment indicated that fibroblast cells were able to respond to variations in
      the underlying surface chemistry, transmitted by the different orientation
      adopted by zein on the different substrates. This property may be useful in
      controlling the spatial distribution of cells on patterned protein layers.

PMID- 18325862
TI  - Porous scaffold of gelatin-starch with nanohydroxyapatite composite processed via
      novel microwave vacuum drying.
AB  - Hydroxyapatite (HA) is a fundamental mineral-based biomaterial, used for
      preparing composites for bone repair and regeneration. Gelatin blended with
      starch results in scaffold composites with enhanced mechanical properties. A
      gelatin-starch blend reinforced with HA nanocrystals (nHA) gave biocompatible
      composites with enhanced mechanical properties. In this study, a porous scaffold
      of gelatin-starch-nHA composites was fabricated through microwave vacuum drying
      and crosslinking using trisodium citrate. Three different composite scaffolds
      were prepared at three different percentages of nHA: 20%, 30% and 40%. The
      microstructures and compositions of the composites were analyzed. Within the
      porous structure, the nHA crystals were observed to precipitate. The interaction
      between the gelatin-starch network film and nHA crystalline material was studied
      using Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction
      analysis (XRD). XRD reflections showed that there are two different minerals
      present in the scaffold composite. There were strong reflection peaks close to
      the 26 degrees and 32 degrees 2theta angles of HA, and close to the 8 degrees and
      49 degrees 2theta angles for sodium citrate minerals. The FTIR result suggested
      that carboxyl groups, C=O and amino groups play crucial roles in HA formation on
      the surface of a gelatin network.

PMID- 18325863
TI  - Advanced enteral therapy in acute pancreatitis: is there a room for
      immunonutrition? A meta-analysis.
AB  - BACKGROUND: It is believed that certain nutrients such as glutamine, arginine and
      omega-3 fatty acids may play a significant role in metabolic, inflammatory, and
      immune processes in acute pancreatitis. The present systematic review aimed to
      define whether the addition of these substances to enteral nutrition provides any
      clinical benefit over standard enteral formulas in patients with acute
      pancreatitis. METHODS: A computerized search on electronic databases (Cochrane
      Central Register of Controlled Trials, EMBASE and MEDLINE) and manual search of
      the abstracts of major gastroenterological meetings (UEGW, DDW) were undertaken.
      The studied outcomes were total infectious complication, in-hospital mortality
      and length of hospital stay. The data were meta-analyzed using a random-effects
      model. RESULTS: A total of three randomized controlled trials satisfied the
      inclusion criteria. When compared with standard enteral nutrition,
      immunonutrition was not associated with the significantly reduced risk of total
      infectious complications (risk ratio 0.82; 95% confidence interval 0.44-1.53;
      P=0.53) and death (risk ratio 0.64; 95% confidence interval 0.20-2.07; P=0.46).
      Mean difference in length of hospital stay between two groups was not significant
      (P=0.80). CONCLUSIONS: There is no evidence that enteral nutrition supplemented
      with glutamine, arginine and/or omega-3 fatty acids, in comparison with standard
      enteral nutrition, has any beneficial effect on infectious complications,
      mortality or length of hospital stay in acute pancreatitis. The pursuit of new
      compositions of enteral formulations in this category of patients may be
      advocated.

PMID- 18325864
TI  - 'Turbaned' forehead flap.

PMID- 18325865
TI  - Symptomatology and correction of the posteriorly-rotated ear.

PMID- 18325866
TI  - Visualizing mineral binding and uptake of bisphosphonate by osteoclasts and non
      resorbing cells.
AB  - Bisphosphonates (BPs) target bone due to their high affinity for calcium ions.
      During osteoclastic resorption, these drugs are released from the acidified bone
      surface and taken up by osteoclasts, where they act by inhibiting the prenylation
      of small GTPases essential for osteoclast function. However, it remains unclear
      exactly how osteoclasts internalise BPs from bone and whether other cells in the
      bone microenvironment can also take up BPs from the bone surface. We have
      investigated this using a novel fluorescently-labelled alendronate analogue (FL
      ALN), and by examining changes in protein prenylation following treatment of
      cells with risedronate (RIS). Confocal microscopic analysis showed that FL-ALN
      was efficiently internalised from solution or from the surface of dentine by
      resorbing osteoclasts into intracellular vesicles. Accordingly, unprenylated
      Rap1A accumulated to the same extent whether osteoclasts were cultured on RIS
      coated dentine or with RIS in solution. By contrast, J774 macrophages
      internalised FL-ALN and RIS from solution, but took up comparatively little from
      dentine, due to their inability to resorb the mineral. Calvarial osteoblasts and
      MCF-7 tumour cells internalised even less FL-ALN and RIS, both from solution and
      from the surface of dentine. Accordingly, the viability of J774 and MCF-7 cells
      was drastically reduced when cultured with RIS in solution, but not when cultured
      on dentine pre-coated with RIS. However, when J774 macrophages were co-cultured
      with rabbit osteoclasts, J774 cells that were adjacent to resorbing osteoclasts
      frequently internalised more FL-ALN than J774 cells more distant from
      osteoclasts. This was possibly a result of increased availability of BP to these
      J774 cells due to transcytosis through osteoclasts, since FL-ALN partially co
      localised with trancytosed, resorbed matrix protein within osteoclasts. In
      addition, J774 cells occupying resorption pits internalised more FL-ALN than
      those on unresorbed surfaces. These data demonstrate that osteoclasts are able to
      take up large amounts of BP, due to their ability to release the BP from the
      dentine surface during resorption. By contrast, non-resorbing cells take up only
      small amounts of BP that becomes available due to natural desorption from the
      dentine surface. However, BP uptake by non-resorbing cells can be increased when
      cultured in the presence of resorbing osteoclasts.

PMID- 18325867
TI  - Preface. Modelling and control of transport and communication networks.

PMID- 18325868
TI  - Mathematical programs with complementarity constraints in traffic and
      telecommunications networks.
AB  - Given a suitably parametrized family of equilibrium models and a higher level
      criterion by which to measure an equilibrium state, mathematical programs with
      equilibrium constraints (MPECs) provide a framework for improving or optimizing
      the equilibrium state. An example is toll design in traffic networks, which
      attempts to reduce total travel time by choosing which arcs to toll and what toll
      levels to impose. Here, a Wardrop equilibrium describes the traffic response to
      each toll design. Communication networks also have a deep literature on
      equilibrium flows that suggest some MPECs. We focus on mathematical programs with
      complementarity constraints (MPCCs), a subclass of MPECs for which the lower
      level equilibrium system can be formulated as a complementarity problem and
      therefore, importantly, as a nonlinear program (NLP). Although MPECs and MPCCs
      are typically non-convex, which is a consequence of the upper level objective
      clashing with the users' objectives in the lower level equilibrium program, the
      last decade of research has paved the way for finding local solutions of MPCCs
      via standard NLP techniques.

PMID- 18325869
TI  - Flow-level performance and user mobility in wireless data networks.
AB  - Channel conditions in wireless networks exhibit huge variations across space and
      time, giving rise to vast fluctuations in the transmission rates. Channel-aware
      scheduling strategies provide an effective mechanism for improving throughput
      performance by exploiting such rate variations, and these have been extensively
      examined at the packet level for a static user configuration. In this paper, we
      discuss the performance implications at the flow level for a dynamic user
      population, taking into account variations on a slower time scale and wide-range
      user mobility as well. First of all, we present simple necessary conditions for
      flow-level stability and prove that these are in fact (near) sufficient for a
      wide family of utility-based scheduling strategies. It is further shown how the
      flow-level performance of the proportional fair scheduling strategy may be
      evaluated by means of a processor-sharing model with a state-dependent service
      rate. In addition, we examine the impact of variations on a slower time scale,
      and establish that the so-called fluid and quasi-stationary regimes yield
      explicit, insensitive performance bounds. Finally, we turn our attention to a
      network of several base stations (BSs) with handoffs of active sessions governed
      by wide-range user mobility. It is demonstrated that mobility increases the
      capacity, not only in the case of globally optimal scheduling but also when each
      of the BSs adheres to a local fair-sharing discipline.

PMID- 18325870
TI  - Too expensive to meter: the influence of transaction costs in transportation and
      communication.
AB  - Technology appears to be making fine-scale charging (as in tolls on roads that
      depend on time of day or even on current and anticipated levels of congestion)
      increasingly feasible. Such charging also appears to be increasingly desirable,
      as traffic on roads continues to grow and costs and public opposition limit new
      construction. Similar incentives towards fine-scale charging also appear to be
      operating in communications and other areas, such as electricity usage. Standard
      economic theory supports such measures and technology is being developed and
      deployed to implement them. But their spread is not very rapid and their
      prospects for the future are uncertain. This paper presents a collection of
      sketches, ranging from ancient history to very recent developments, that
      illustrate the costs that charging imposes. Some of those costs are explicit (in
      terms of the monetary costs to users and the costs of implementing the charging
      mechanisms). Others are implicit, such as the time or the mental processing costs
      of users. These argue that the case for fine-scale charging is not unambiguous
      and that in many cases such charging may lead to undesirable outcomes.

PMID- 18325871
TI  - Control of communication networks: welfare maximization and multipath transfers.
AB  - We discuss control strategies for communication networks such as the Internet. We
      advocate the goal of welfare maximization as a paradigm for network resource
      allocation. We explore the application of this paradigm to the case of parallel
      network paths. We show that welfare maximization requires active balancing across
      paths by data sources, and potentially requires implementation of novel transport
      protocols. However, the only requirement from the underlying 'network layer' is
      to expose the marginal congestion cost of network paths to the 'transport layer'.
      We further illustrate the versatility of the corresponding layered architecture
      by describing transport protocols with the following properties: they welfare
      maximization, each communication may use an arbitrary collection of paths, where
      paths may be from an overlay, and paths may be combined in series and parallel.
      We conclude by commenting on incentives, pricing and open problems.

PMID- 18325872
TI  - Data, modelling and inference in road traffic networks.
AB  - In this paper, we study UK road traffic data and explore a range of modelling and
      inference questions that arise from them. For example, loop detectors on the M25
      motorway record speed and flow measurements at regularly spaced locations as well
      as the entry and exit lanes of junctions. An exploratory study of these data
      helps us to better understand and quantify the nature of congestion on the road
      network. From a traveller's perspective it is crucially important to understand
      the overall journey times and we look at methods to improve our ability to
      predict journey times given access jointly to both real-time and historical loop
      detector data. Throughout this paper we will comment on related work derived from
      US freeway data.

PMID- 18325873
TI  - Mechanisms for spatio-temporal pattern formation in highway traffic models.
AB  - A key qualitative requirement for highway traffic models is the ability to
      replicate a type of traffic jam popularly referred to as a phantom jam, shock
      wave or stop-and-go wave. Despite over 50 years of modelling, the precise
      mechanisms for the generation and propagation of stop-and-go waves and the
      associated spatio-temporal patterns are in dispute. However, the increasing
      availability of empirical datasets, such as those collected from motorway
      incident detection and automatic signalling system (MIDAS) inductance loops in
      the UK or the next-generation simulation trajectory data (NGSIM) project in the
      USA, means that we can expect to resolve these questions definitively in the next
      few years. This paper will survey the essence of the competing explanations of
      highway traffic pattern formation and introduce and analyse a new mechanism,
      based on dynamical systems theory and bistability, which can help resolve the
      conflict.

PMID- 18325874
TI  - Topological modelling of large networks.
AB  - In a complex network, there is a strong interaction between the network's
      topology and its functionality. A good topological network model is a practical
      tool as it can be used to test 'what-if' scenarios and it can provide predictions
      of the network's evolution. Modelling the topology structure of a large network
      is a challenging task, since there is no agreement in the research community on
      which properties of the network a model should be based, or how to test its
      accuracy. Here we present recent results on how to model a large network, the
      autonomous system (AS)-Internet, using a growth model. Based on a nonlinear
      preferential growth model and the reproduction of the network's rich club, the
      model reproduces many of the topological characteristics of the AS-Internet. We
      also identify a recent method to visualize the network's topology. This
      visualization technique is simple and fast and can be used to understand the
      properties of a large complex network or as a first step to validate a network
      model.

PMID- 18325875
TI  - Attacker-defender models and road network vulnerability.
AB  - The reliability of road networks depends directly on their vulnerability to
      disruptive incidents, ranging in severity from minor disruptions to terrorist
      attacks. This paper presents a game theoretic approach to the analysis of road
      network vulnerability. The approach posits predefined disruption, attack or
      failure scenarios and then considers how to use the road network so as to
      minimize the maximum expected loss in the event of one of these scenarios coming
      to fruition. A mixed route strategy is adopted, meaning that the use of the road
      network is determined by the worst scenario probabilities. This is equivalent to
      risk-averse route choice. A solution algorithm suitable for use with standard
      traffic assignment software is presented, thereby enabling the use of electronic
      road navigation networks. A variant of this algorithm suitable for risk-averse
      assignment is developed. A numerical example relating to the central London road
      network is presented. The results highlight points of vulnerability in the road
      network. Applications of this form of network vulnerability analysis together
      with improved solution methods are discussed.

PMID- 18325876
TI  - Transport networks and their use: how real can modelling get?
AB  - The context for modelling transport systems and their use is set out. Such
      modelling is based on representing the transport system by a network of nodes and
      links, and the characteristics of this representation needed to reflect the
      principal realities of the system are outlined. The characteristics of use of the
      system that need to be reflected are described. Purposes of the modelling are set
      out and its evolution is described, starting from the basic traffic assignment
      model and discussing its generalizations and extensions in the search for greater
      realism-first in steady-state modelling for fixed demand, and then considering
      variable demand and time dependence. Further progress towards appropriate realism
      is seen as requiring communication and cooperation between the modellers and the
      users of models, helped perhaps by combining the advantages of analytical
      modelling and microsimulation.

PMID- 18325877
TI  - Discussion.

PMID- 18325878
TI  - Optimal resource allocation for multicast sessions in multi-hop wireless
      networks.
AB  - In this paper, we extend recent results on fair and stable resource allocation in
      wireless networks to include multicast sessions, in particular multi-rate
      multicast. The solution for multi-rate multicast is based on scheduling virtual
      (shadow) 'traffic' that 'moves' in reverse direction from destinations to
      sources. This shadow scheduling algorithm can also be used to control delays in
      wireless networks.

PMID- 18325879
TI  - Human mobility models and opportunistic communications system design.
AB  - In this paper, we seek to improve understanding of the structure of human
      mobility, with a view to using this for designing algorithms for the
      dissemination of data among mobile users. We analyse community structures and
      node centrality from the human mobility traces and use these two metrics to
      design efficient forwarding algorithms in terms of delivery ratio and delivery
      cost for mobile networks. This is the first empirical study of community and
      centrality using real human mobility datasets.

PMID- 18325880
TI  - Congestion, ramp metering and tolls.
AB  - The cell transmission model of a freeway is used to compare four congestion
      reducing schemes: (R) ramp control only; (T) one lane is tolled and ramps are
      uncontrolled; (B) bottlenecks are tolled and ramps are uncontrolled; and (RB)
      ramps are controlled and bottlenecks are tolled. In the base case, ramps are
      uncontrolled and there are no tolls. It is found that (T) is inefficient and may
      leave all travellers worse off; (R), (B) and (RB) can achieve efficient freeway
      use; (B) can eliminate queues, but has adverse spatial and equity side effects;
      (RB) minimizes these side effects. (RB) is likely to be least costly to implement
      and maintain.

PMID- 18325881
TI  - The interpretation of abnormal 31P magnetic resonance saturation transfer
      measurements of Pi/ATP exchange in insulin-resistant skeletal muscle.

PMID- 18325883
TI  - A randomized controlled clinical trial of 2295 ultrasound-guided embryo
      transfers.
AB  - BACKGROUND: We wanted to test the hypothesis that using abdominal ultrasound at
      the time of embryo transfer to guide replacement, improved pregnancy rates by at
      least 5%. METHODS: An RCT in a large assisted conception unit. A pilot study and
      power calculation suggested that at least 2000 embryo transfers were required to
      demonstrate a difference of 5%, for a test with 80% power and Type 1 error 0.05.
      Randomization, data entry and analysis were arranged independently. Randomization
      was stratified for age and fresh/frozen embryo transfer. Analysis was by
      intention to treat. RESULTS: There was no difference in clinical pregnancy or
      live birth rates between the two groups. The clinical pregnancy rate for
      ultrasound-guided embryo transfer was 22% and for non-ultrasound-guided embryo
      transfer was 23% (odds ratio: 0.96; 95% confidence interval: 0.79-1.18).
      CONCLUSIONS: We set out to determine whether ultrasound-guided embryo transfer
      improved clinical pregnancy rates and live birth rates in assisted conception. We
      used an appropriately powered RCT design. We did not demonstrate a difference.
      This outcome is at odds with the UKs National Institute of Clinical Excellence
      recommendations for fertility treatment (Fertility Assessment and Treatment for
      People with Fertility Problems. London, UK: RCOG Press, 2004, 112.) which used a
      meta-analysis of four smaller trials (range 362-800 patients, totalling 2051
      embryo transfers) to conclude that ultrasound should be offered. We suggest that
      the current Cochrane review should be updated with data from our trial and
      recommend that consideration is given to accounting for heterogeneity between the
      included trials.

PMID- 18325884
TI  - Protective effect of antioxidant supplementation in sperm-preparation medium
      against oxidative stress in human spermatozoa.
AB  - BACKGROUND: Oxidative stress induced by reactive oxygen species (ROS) is
      associated with an impaired fertilization ability of spermatozoa. We investigated
      the effects of adding antioxidants to a sperm preparation medium on the
      functional parameters of the spermatozoa. METHODS: Spermatozoa were washed with
      Ham's F-10 media containing the antioxidants, ethylenediaminetetraacetic acid
      (EDTA) and catalase, at various concentrations, and then the ROS levels in sperm
      suspensions, and the forward motility, acrosome reaction, DNA integrity and lipid
      peroxidation of the spermatozoa were assessed. RESULTS: The ROS levels were
      significantly lower in sperm suspensions washed with the antioxidants (196
      approximately 312 rlu; relative light units) than in control sperm (604 rlu, P <
      0.05). The addition of 10 microM EDTA to the sperm preparation medium
      significantly improved the motility of the spermatozoa compared with the control
      group, the groups containing EDTA at other concentrations and the groups
      containing catalase. Catalase significantly increased the acrosome reaction rate
      of the spermatozoa. Both EDTA and catalase significantly decreased the DNA
      fragmentation rate of the spermatozoa. However, the antioxidants did not reduce
      lipid peroxidation. CONCLUSIONS: Supplementing sperm preparation medium with EDTA
      or catalase significantly improved the overall functional parameters of the
      spermatozoa by reducing the ROS levels.

PMID- 18325885
TI  - The impact of partner coping in couples experiencing infertility.
AB  - BACKGROUND: Most studies examining coping with infertility use the individual as
      the unit of analysis. Although valuable, these studies fail to show the impact
      that partner coping has on individual distress. Since infertility is a shared
      stressor, examining the impact of partner coping is particularly relevant.
      METHODS: Data were based on a questionnaire in a consecutive sample of 1169 women
      and 1081 Danish men prior to beginning assisted reproduction treatment.
      Multilevel modeling using the Actor Partner Interdependence Model and follow-up
      analysis of variance were used to examine the couple as the unit of analysis.
      RESULTS: A partner's use of active-avoidance coping was related to the increased
      personal, marital and social distress for men and women. A woman's use of active
      confronting coping was related to increased male marital distress. And a
      partner's use of meaning-based coping was associated with decreased marital
      distress in men and increased social distress in women. CONCLUSIONS: Although
      understudied, partner coping patterns play a key role in a partner's ability to
      cope with the infertility experience. Physicians and mental health providers can
      help couples to understand the coping strategies that lead to increased and
      decreased partner distress.

PMID- 18325886
TI  - Sperm chromatin structure assay parameters measured after density gradient
      centrifugation are not predictive of the outcome of ART.

PMID- 18325887
TI  - Different small-dose sufentanil blunting cardiovascular responses to laryngoscopy
      and intubation in children: a randomized, double-blind comparison.
AB  - BACKGROUND: Sufentanil is a potent opioid analgesic frequently used in clinical
      anaesthesia. This prospective, randomized, double-blind study was designed to
      assess the efficacy of different small-dose sufentanil attenuating the
      cardiovascular intubation response in healthy children, aiming at determining the
      optimal dose of sufentanil for this purpose. METHODS: A total of 165 children
      aged 3-9 yr were randomized to one of four groups to receive the following in a
      double-blind manner: normal saline (Group 1), sufentanil 0.1 microg kg(-1) (Group
      2), sufentanil 0.2 microg kg(-1) (Group 3), and sufentanil 0.3 microg kg(-1)
      (Group 4). Anaesthesia was induced with propofol 2.5 mg kg(-1) and vecuronium 0.1
      mg kg(-1). Non-invasive blood pressure (BP) and heart rate (HR) were recorded
      before induction of anaesthesia (baseline value), at immediately before
      intubation (post-induction values), at intubation, and at 1 min intervals for 5
      min after intubation. The per cent changes of systolic blood pressure (SBP) and
      HR during the observation were calculated. RESULTS: Except for Group 4, tracheal
      intubation caused significant increases in BP and HR in Groups 1, 2, and 3
      compared with baseline values. BP and HR at intubation and their maximum values
      during the observation were significantly different among the four groups. The
      maximum per cent increases of SBP and HR during the observation were 20 and 28%
      of baseline values, respectively, in Group 2, 13 and 13% in Group 3, and 0 and 4%
      in Group 4 compared with 24 and 37% in Group 1. Except for the Group 3 vs Group 4
      comparison, the incidences of SBP and HR per cent increases >30% of baseline
      values were also significantly different among the four groups. CONCLUSIONS: In
      combination with propofol for induction of anaesthesia in children, the bolus
      administration of sufentanil can produce a dose-related attenuation of the
      cardiovascular intubation response and sufentanil 0.3 microg kg(-1) can
      completely abolish the cardiovascular intubation response.

PMID- 18325888
TI  - Cutting edge: a naturally occurring mutation in CD1e impairs lipid antigen
      presentation.
AB  - The human CD1a-d proteins are plasma membrane molecules involved in the
      presentation of lipid Ags to T cells. In contrast, CD1e is an intracellular
      protein present in a soluble form in late endosomes or lysosomes and is essential
      for the processing of complex glycolipid Ags such as hexamannosylated
      phosphatidyl-myo-inositol, PIM(6). CD1e is formed by the association of beta(2)
      microglobulin with an alpha-chain encoded by a polymorphic gene. We report here
      that one variant of CD1e with a proline at position 194, encoded by allele 4,
      does not assist PIM(6) presentation to CD1b-restricted specific T cells. The
      immunological incompetence of this CD1e variant is mainly due to inefficient
      assembly and poor transport of this molecule to late endosomal compartments.
      Although the allele 4 of CD1E is not frequent in the population, our findings
      suggest that homozygous individuals might display an altered immune response to
      complex glycolipid Ags.

PMID- 18325889
TI  - Villous explant culture using early gestation tissue from ongoing pregnancies
      with known normal outcomes: the effect of oxygen on trophoblast outgrowth and
      migration.
AB  - BACKGROUND: Early placental and embryo development occur in a physiologically low
      oxygen environment, with a rise in oxygen tension within the placenta towards the
      end of the first trimester. Oxygen is implicated in the regulation of trophoblast
      differentiation and invasion. This study examined the effects of oxygen tension
      on extravillous trophoblast outgrowth and migration from normal pregnancies free
      of significant pathology. METHODS: Early gestation villous tissue (11-14 weeks
      gestation), obtained by chorionic villus sampling, was cultured in 3 or 20%
      oxygen. Maternal and fetal outcomes were ascertained for all samples. The
      frequency and amount of trophoblast outgrowth and migration from villi were
      measured for up to 192 h. RESULTS: Significantly fewer explants produced
      outgrowths in 3% compared with 20% oxygen. The number of sites of trophoblast
      outgrowth and the extent of migration were also significantly less in 3% compared
      with 20% oxygen. In vitro hypoxia/reoxygenation further reduced trophoblast
      growth compared with 3% oxygen alone. HLA-G expression in extravillous
      trophoblasts was not affected by oxygen tension, with HLA-G positive extravillous
      trophoblasts being universally Ki67 negative. CONCLUSION: Human placental villi
      and extravillous trophoblasts in the late first trimester of pregnancy are
      sensitive to oxygen tension, with low oxygen inhibiting extravillous trophoblast
      outgrowth and migration.

PMID- 18325890
TI  - Fatal left internal mammary artery graft to subclavian vein fistula complicating
      dual-chamber pacemaker implantation.
AB  - We describe the case of a 75-year-old woman with an iatrogenic fistula between a
      left internal mammary artery graft to the left anterior descending coronary
      artery and the left subclavian vein that developed after implantation of a dual
      chamber pacemaker.

PMID- 18325891
TI  - Successful slow pathway ablation for atrioventricular nodal re-entrant
      tachycardia via a hypoplastic inferior vena cava in a patient with an azygos
      continuation.
AB  - Catheter ablation of the slow pathway for atrioventricular nodal re-entrant
      tachycardia (AVNRT) is not always possible due to congenital or acquired
      obstruction of the inferior vena cava (IVC). Although a superior access has been
      proposed as an alternative approach, a poor manoeuvrability and a lower stability
      of the ablation catheter may be potential problems. We report a case of slow
      pathway ablation for AVNRT in a patient with an azygos continuation using a
      hypoplastic but uninterrupted IVC.

PMID- 18325892
TI  - Implantable loop recorder for recurrent syncope: influence of cardiac conduction
      abnormalities showing up on resting electrocardiogram and of underlying cardiac
      disease on follow-up developments.
AB  - AIMS: The implantable loop recorder is a useful diagnostic tool in dealing with
      recurrent syncope in patients. We tested to determine the influence of cardiac
      conduction abnormalities that turn up on resting electrocardiogram (ECG) and the
      impact of underlying cardiac disease on developments during follow-up. METHODS
      AND RESULTS: Ninety-five consecutive patients received an implantable loop
      recorder to monitor recurrent syncope (n = 4.9+/-3.8) of unknown aetiology after
      cardiac investigations, including an electrophysiological study. Resting ECG was
      abnormal, suggesting an arrhythmic syncope, in 29 (30.5%) patients, while 21
      (22.1%) patients had an underlying cardiac disease. During an average follow-up
      period of 10.2+/-5.2 months, 43 (45.2%) patients developed a new syncope
      associated in 27 of them (62.8%) with an arrhythmic event. Syncope was no more
      frequent in the subgroup of patients with cardiac conduction abnormalities on
      resting ECG, while the frequency of arrhythmic events was similar whether or not
      the ECG was normal. In the subgroup of patients with cardiac disease with normal
      left ventricular ejection fraction, the occurrence of syncope was less frequent,
      and the number of arrhythmic events was no greater in these patients. CONCLUSION:
      Implantable loop recorder is a useful diagnostic tool for recurrent syncope of
      unknown aetiology.

PMID- 18325893
TI  - Low selection of topoisomerase mutants from strains of Escherichia coli
      harbouring plasmid-borne qnr genes.
AB  - OBJECTIVES: To investigate mutations in the type II topoisomerase genes in
      quinolone-resistant mutants selected from bacteria harbouring plasmid-borne qnr
      genes. METHODS: Mutants were selected by nalidixic acid, ciprofloxacin and
      moxifloxacin from two Escherichia coli reference strains and corresponding
      transconjugants harbouring qnrA1, qnrA3, qnrB2 or qnrS1 genes. RESULTS: The
      proportion of resistant mutants selected by the three quinolones was,
      respectively, in the same range for qnr-positive transconjugants and reference
      strains. Only 20% (65/329) of the mutants selected from the transconjugants
      showed a gyrase mutation, whereas 79% (94/119) of those from the reference
      strains without a qnr gene did (P < 0.0001). At four times the MIC of the
      selector quinolone, gyrA mutants represented 49% and 95% of the mutants selected
      with nalidixic acid, 4% and 94% with ciprofloxacin and 0% and 54% with
      moxifloxacin for qnr-positive transconjugants and reference strains,
      respectively. Mutations within gyrA were distributed at codon 87 (D87G, H, N or
      Y) and at codon 83 (S83L) with three novel mutations (gyrA Ser83stop, gyrA
      Asp82Asn and gyrB insertion of Glu at 465) and three rare mutations (gyrA
      Gly81Asp, gyrA Asp82Gly and gyrA Ser431Pro), mainly obtained from reference
      strains after moxifloxacin selection. Strikingly, none of the mutants selected by
      moxifloxacin from qnr-positive transconjugants harboured a mutation in the
      topoisomerase genes. CONCLUSIONS: Topoisomerase mutants are rarely selected by
      ciprofloxacin and moxifloxacin from strains harbouring qnr. This suggests that
      the quinolone resistance-determining region domains are protected from quinolones
      by the Qnr protein and consequently other mechanisms are developed to acquire a
      further step of fluoroquinolone resistance.

PMID- 18325895
TI  - Development of Escherichia coli rifaximin-resistant mutants: frequency of
      selection and stability.
AB  - OBJECTIVES: To select rifaximin-resistant mutants of Escherichia coli and to
      establish the frequency of mutation, cross-resistance with other antimicrobial
      agents and the stability of the mutants obtained. METHODS: Four E. coli isolates
      [two enteroaggregative E. coli (EAEC) and two enterotoxigenic E. coli (ETEC)]
      were used to obtain rifaximin-resistant mutants. The frequency of mutation in the
      presence of rifaximin, rifampicin and ciprofloxacin was established by growth on
      plates containing serial dilutions of antibiotic above the bacterial MIC. To
      determine the stability of rifaximin resistance, 28 selected resistant mutants
      were grown for 20 consecutive cultures on antibiotic-free plates. Every 10 days,
      the MICs of rifaximin, chloramphenicol, nalidixic acid and ciprofloxacin were
      established. RESULTS: The frequency of mutation in the presence of rifaximin
      ranged between 5.7 x 10(-7) and 1.6 x 10(-6) in the case of the ETEC isolates,
      and between 2.0 x 10(-8) and 9.3 x 10(-8) in the case of the EAEC isolates; the
      frequency of mutation in the presence of rifampicin was in the order of 10(-8)
      and no mutant in the presence of ciprofloxacin was obtained. Twenty-six out of 28
      selected mutants exhibited resistance levels around or higher than 256 mg/L. In
      all cases, the resistance was stable, and no reversion towards the original
      parental MIC was observed. In no case was the MIC of chloramphenicol, nalidixic
      acid or ciprofloxacin affected. CONCLUSIONS: Rifaximin has a low level of
      resistance selection, although it may select stable highly resistant mutants in a
      single step. Periodical surveillance of the levels of rifaximin resistance is
      required to detect the possible appearance of rifaximin-resistant clinical
      isolates. Further studies to characterize in-depth the mechanisms of stable
      resistance to rifaximin are necessary.

PMID- 18325896
TI  - The involvement of HIV-1 RNAse H in resistance to nucleoside analogues.
AB  - Some recent studies have underlined the role of the entire reverse transcriptase
      (RT) and in particular its carboxy-terminal domain from amino acid 427 to amino
      acid 560 [the ribonuclease H (RNAse H) domain] in resistance to nucleoside RT
      inhibitors (NRTIs). RNAse H is implicated in catalysing the degradation of the
      RNA strand during conversion of the viral genome into double-stranded DNA. It has
      been shown, by site-directed mutagenesis, that amino acid substitutions in the
      RNAse H domain could affect the binding enzyme/substrate, resulting in a decrease
      in the RNAse H activity. For example, mutations at positions 478, 539 and 549 led
      to a slowing down in the degradation of the RNA strand. In vitro, the mutations
      H539N and D549N decreased the frequency of RT template-switching and, thereby,
      increased the time for excision of incorporated NRTIs, and thus enhanced NRTI
      resistance. It has been confirmed in vivo that mutations at position 558 were
      statistically associated with a number of thymidine analogue mutations in a study
      including 144 HIV-1 patients, suggesting that it could be an accessory mutation
      that could reinforce NRTI resistance. This article highlights evidence that
      mutations in RNAse H can enhance NRTI resistance, suggesting that phenotypic and
      genotypic analyses of clinical samples including the entire HIV-1 RT and in
      particular the RNAse H domain are now required to better characterize the in vivo
      role of the RNAse H mutations on susceptibility and response to NRTIs in HIV-1
      infected patients.

PMID- 18325897
TI  - A road map for universal coverage: finding a pass through the financial
      mountains.
AB  - Government already pays for more than half of U.S. health care costs, and nearly
      all universal health insurance proposals assume continued government involvement
      through tax subsidies and other means. The question of what specific taxes could
      be used to finance universal coverage is, however, seldom carefully examined, in
      part due to efforts by health care reform proponents to downplay tax issues. In
      this article we undertake such an examination. We argue that the challenges of
      relying on taxes for universal coverage are even greater than is generally
      appreciated, but that they can nevertheless be met. A proposal to fund a
      universal health insurance voucher system with a value-added tax illustrates
      issues that would arise for tax-financed plans in general and provides a broad
      framework for a bipartisan approach to universal coverage. We discuss significant
      problems that such an approach would face and suggest solutions. We outline a
      long-term political and legislative strategy for enacting universal coverage that
      draws upon precedents set by comparable legislative initiatives, including tax
      reform and Medicare. The results are an improved understanding of the
      relationship between systemic health care finance reform and taxation and a
      politically realistic plan for universal coverage that employs undisguised taxes.

PMID- 18325898
TI  - Governance and community benefit: are nonprofit hospitals good candidates for
      Sarbanes-Oxley type reforms?
AB  - Recent investigations into the activities of nonprofit hospitals have pointed to
      weak or lax governance on the part of some of these organizations. As a result of
      these events, various federal and state initiatives are now either under way or
      under discussion to strengthen the governance of hospitals and other nonprofit
      corporations through mandatory board structures and practices. However, despite
      policy makers' growing interest in these types of governance reforms, there is in
      fact little empirical evidence to support their contribution to the effectiveness
      of hospital boards. The purpose of this article is to report the results of a
      study examining the relationship between the structure and practices of nonprofit
      hospital boards relative to the hospital's provision of community benefits. Our
      results point to modest relationships between these sets of variables, suggesting
      considerable limitations to what federal and state policy makers can accomplish
      through legislative initiatives to improve the governance of nonprofit hospitals.

PMID- 18325899
TI  - Role of budget impact in drug reimbursement decisions.
AB  - There are three known criteria that underlie drug reimbursement decisions:
      therapeutic value, cost-effectiveness, and burden of disease. However, evidence
      from recent reimbursement decisions in several jurisdictions points to residual,
      unexplained variables, among which is budget impact. Budget impact refers to the
      total costs that drug reimbursement and use entail with respect to one part of
      the health care system, pharmaceutical care, or to the entire health care system,
      taking into account the possible reallocation of resources across budgets or
      sectors of the health care system. The economic and equity rationale for carrying
      out budget impact analyses is opportunity cost, or benefits forgone, measured in
      terms of utility or equitable distribution, by using resources in one way rather
      than another. In other words, by choosing to draw down the budget in one way,
      decision makers forgo other opportunities to use the same resources. Under a set
      of unrealistic assumptions, cost-effectiveness analysis accounts for opportunity
      cost while conveying to the decision maker the price of maximizing health gains,
      subject to a budget or resource constraint. However, the underlying assumptions
      are implausible, particularly in the context of pharmaceutical care. Moreover,
      budget impact analysis is more useful to the decision maker than cost
      effectiveness analysis if the objective is not to maximize health gains subject
      to a budget or resource constraint, but to reduce variance in health gains. With
      respect to equitable distribution, budget impact analyses lay bare the
      individuals or groups who lose out - those who bear the opportunity cost of
      spending resources in accordance with one decision rule rather than another.

PMID- 18325900
TI  - Balancing regulatory controls and incentives: toward smarter and more transparent
      oversight in long-term care.
AB  - Government oversight of long-term care involves inspections of patients' records,
      limited observations of patients and care practices, reviews of policies and
      procedures, and distribution of publicly available information. Although many
      providers bemoan the stifling consequences of excessive regulation, oversight in
      this area remains a highly legitimate endeavor for the public, though the public
      has limited trust in the existing regulatory regime. This distrust stems from
      many sources, not least of which includes considerable variation, both within and
      across states, in the way government oversight occurs. Reforming the current
      regulatory structure requires that we regulate "smarter" and more consistently.
      This means improving and maximizing use of the data already being collected, but
      it also means explicitly rationalizing the regulator's responsibility to review
      performance and apply sanctions when necessary. Oversight should more closely
      resemble consultancy, with regulators sharing information with providers about
      how to improve quality. Ideally, there needs to be an iterative process in which
      state inspectors identify performance problems and the nation's quality
      improvement organizations then help providers design quality improvement
      interventions to ameliorate the problems identified. The benefits of a revised
      regulatory approach are especially apparent in the aftermath of Hurricane
      Katrina, where more effective oversight would have identified nursing home
      residents at risk for low-quality care before the disaster occurred while better
      identifying those in need of evacuation or assistance afterward.

PMID- 18325901
TI  - Alaska public health law reform.
AB  - The Turning Point Model State Public Health Act (Turning Point Act), published in
      September 2003, provides a comprehensive template for states seeking public
      health law modernization. This case study examines the political and policy
      efforts undertaken in Alaska following the development of the Turning Point Act.
      It is the first in a series of case studies to assess states' consideration of
      the Turning Point Act for the purpose of public health law reform. Through a
      comparative analysis of these case studies and ongoing legislative tracking in
      all fifty states, researchers can assess (1) how states codify the Turning Point
      Act into state law and (2) how these modernized state laws influence or change
      public health practice, leading to improved health outcomes.

PMID- 18325902
TI  - Attrition in the RAND Health Insurance Experiment: a response to Nyman.
AB  - In a prior article in this journal, John Nyman argues that the effect on health
      care use and spending found in the RAND Health Insurance Experiment is an
      artifact of greater voluntary attrition in the cost-sharing plans relative to the
      free care plan. Specifically, he speculates that those in the cost-sharing plans,
      when faced with a hospitalization, withdrew. His argument is implausible because
      (1) families facing a hospitalization would be worse off financially by
      withdrawing; (2) a large number of observational studies find a similar effect of
      cost sharing on use; (3) those who left did not differ in their utilization prior
      to leaving; (4) if there had been no attrition and cost sharing did not reduce
      hospitalization rates, each adult in each family that withdrew would have had to
      have been hospitalized once each year for the duration of time they would
      otherwise have been in the experiment, an implausibly high rate; (5) there are
      benign explanations for the higher attrition in the cost-sharing plans. Finally,
      we obtained follow-up health-status data on the great majority of those who left
      prematurely. We found the health-status findings were insensitive to the
      inclusion of the attrition cases.

PMID- 18325904
TI  - Misleading congress about drug development: Reply.
AB  - The review essay by Donald Light about a Congressional Budget Office report on
      pharmaceutical research and development (R&D) (Light 2007) contains factual
      errors, leaves the reader uninformed about rebuttal responses to criticisms made
      in the review about studies of R&D costs, and draws erroneous conclusions about
      the nature of industry economics.

PMID- 18325906
TI  - C3 R102G polymorphism increases risk of age-related macular degeneration.
AB  - Inflammation has long been suspected to play a role in the pathogenesis of age
      related macular degeneration (AMD). Association of variants in the complement
      factor H (CFH) and complement factor B (CFB) genes has targeted the search for
      additional loci to the alternative complement cascade, of which C3 is a major
      component. Two non-synonymous coding polymorphisms within C3, R102G and L314P,
      have previously been strongly associated with increased risk. These variants are
      in strong linkage disequilibrium (LD), making the contribution of this locus to
      AMD even more difficult to ascertain. We sought to determine whether the C3
      association resulted primarily from only one of these two variants or from a
      combined effect of both in 223 families and an independent dataset of 701 cases
      and 286 unrelated controls. The C3 polymorphisms were in strong LD (r(2) = 0.85),
      and both were associated in the family-based and case-control datasets (R102G
      genoPDT P = 0.02, case-control genotypic P = 0.004; L314P genoPDT P = 0.001, case
      control genotypic P = 0.04). In conditional analyses in the case-control dataset,
      R102G remained associated with disease in the L314P risk allele carriers (P =
      0.01), but there was no effect of L314P in the R102G risk allele carriers (P =
      0.2). After adjusting for age, smoking, CFH Y402H, LOC387715 A69S, and CFB R32Q,
      the effect of R102G remained strong [P = 0.015, odds ratio = 1.55, 95% confidence
      interval 1.09 to 2.21, adjusted PAR(population attributable risk) = 0.17].
      Therefore, while the strong LD between R102G and L314P makes it difficult to
      disentangle their individual effects on disease risk, the R102G polymorphism
      acting alone provides the best model for disease in our data.

PMID- 18325907
TI  - A functional SNP in EDG2 increases susceptibility to knee osteoarthritis in
      Japanese.
AB  - Osteoarthritis (OA) is the most common form of arthritis and is characterized by
      the gradual loss of articular cartilage. Several OA-susceptibility genes have
      been identified; however, there are few pharmaceutical targets that can be
      targeted with small-molecule compounds. To investigate whether a susceptibility
      gene for OA exists among G-protein-coupled receptors (GPCRs), we performed a
      stepwise association study for 167 single nucleotide polymorphisms (SNPs) in 44
      GPCR genes that were present in cartilage. Through the stepwise association
      study, an SNP located in the promoter region of EDG2 [endothelial
      differentiation, lysophosphatidic acid (LPA) GPCR, 2] (-2,820G/A; rs10980705)
      showed significant association with knee OA in two independent populations
      (pooled P = 2.6 x 10(-5)). Luciferase and electrophoretic mobility shift assays
      indicate that this SNP exerts an allelic difference on transcriptional activity
      and DNA binding in synovial cells, with the susceptibility allele showing
      increased activity and binding. EDG2 encodes an LPA receptor dominantly expressed
      in the synovium. The LPA receptor increased the expression of inflammatory
      cytokines and matrix metalloproteases in synovial cells. Our findings suggest
      that the LPA-EDG2 signal is involved in the pathogenesis of OA via catabolic
      process.

PMID- 18325908
TI  - R125W coding variant in TBC1D1 confers risk for familial obesity and contributes
      to linkage on chromosome 4p14 in the French population.
AB  - Stone et al. previously reported an association between the TBC1D1 gene variant
      R125W (rs35859249) and severe obesity in women from US pedigrees. We attempted to
      replicate this result in 9714 French Caucasian individuals, combining family
      based and general population studies. We confirmed an association with familial
      obesity (defined as body mass index (BMI) > or = 97th percentile) in women from
      1109 obesity-selected pedigrees (Z-score = 2.70, P = 0.008). Analysis of 16
      microsatellite markers on chromosome 4 restricted to the 42 pedigrees carrying
      the TBC1D1 R125W variant allele also revealed a suggestive evidence of linkage
      with obesity (maximum likelihood binomial LOD of 2.73, P = 0.0002) on chromosome
      4p14, where resides TBC1D1. In contrast, R125W variant was neither associated
      with BMI nor with obesity in a large population-based cohort. These results
      confirm a putative role of TBC1D1 R125W variant in familial obesity
      predisposition.

PMID- 18325909
TI  - Subnuclear localization and mobility are key indicators of PAX3 dysfunction in
      Waardenburg syndrome.
AB  - Mutations in the transcription factor PAX3 cause Waardenburg syndrome (WS) in
      humans and the mouse Splotch mutant, which display similar neural crest-derived
      defects. Previous characterization of disease-causing mutations revealed
      pleiotropic effects on PAX3 DNA binding and transcriptional activity. In this
      study, we evaluated the impact of disease alleles on PAX3 localization and
      mobility. Immunofluorescence analyses indicated that the majority of PAX3
      occupies the interchromatin space, with only sporadic colocalization with sites
      of transcription. Interestingly, PAX3 disease alleles fell into two distinct
      categories when localization and dynamics in fluorescence recovery after
      photobleaching (FRAP) were assessed. The first group (class I), comprising N47H,
      G81A and V265F exhibit a diffuse distribution and markedly increased mobility
      when compared with wild-type PAX3. In contrast, the G42R, F45L, S84F, Y90H and
      R271G mutants (class II) display evidence of subnuclear compartmentalization and
      mobility intermediate between wild-type PAX3 and class I proteins. However,
      unlike class I mutants, which retain DNA binding, class II proteins are deficient
      for this activity, indicating that DNA binding is not a primary determinant of
      PAX3 distribution and movement. Importantly, class I properties prevail when
      combined with a class II mutation, which taken with the proximity of the two
      mutant classes within the PAX3 protein, suggests class I mutants act by
      perturbing PAX3 conformation. Together, these results establish that altered
      localization and dynamics play a key role in PAX3 dysfunction and that loss of
      the underlying determinants represents the principal defect for a subset of
      Waardenburg mutations.

PMID- 18325910
TI  - Genome-wide association scans identified CTNNBL1 as a novel gene for obesity.
AB  - Obesity is a major public health problem with strong genetic determination;
      however, the genetic factors underlying obesity are largely unknown. In this
      study, we performed a genome-wide association scan for obesity by examining
      approximately 500 000 single-nucleotide polymorphisms (SNPs) in a sample of 1000
      unrelated US Caucasians. We identified a novel gene, CTNNBL1, which has multiple
      SNPs associated with body mass index (BMI) and fat mass. The most significant
      SNP, rs6013029, achieved experiment-wise P-values of 2.69 x 10(-7) for BMI and of
      4.99 x 10(-8) for fat mass, respectively. The SNP rs6013029 minor allele T
      confers an average increase in BMI and fat mass of 2.67 kg/m(2) and 5.96 kg,
      respectively, compared with the alternative allele G. We further genotyped the
      five most significant CTNNBL1 SNPs in a French case-control sample comprising 896
      class III obese adults (BMI > or = 40 kg/m(2)) and 2916 lean adults (BMI < 25
      kg/m(2)). All five SNPs showed consistent associations with obesity (8.83 x 10(
      3) < P < 6.96 x 10(-4)). Those subjects who were homozygous for the rs6013029 T
      allele had 1.42-fold increased odds of obesity compared with those without the T
      allele. The protein structure of CTNNBL1 is homologous to beta-catenin, a family
      of proteins containing armadillo repeats, suggesting similar biological
      functions. beta-Catenin is involved in the Wnt/beta-catenin-signaling pathway
      which appears to contribute to maintaining the undifferentiated state of pre
      adipocytes by inhibiting adipogenic gene expression. Our study hence suggests a
      novel mechanism for the development of obesity, where CTNNBL1 may play an
      important role. Our study also provided supportive evidence for previously
      identified associations between obesity and INSIG2 and PFKP, but not FTO.

PMID- 18325911
TI  - Can schools promote the health of children with asthma?
AB  - This report describes the evaluation of a whole-school intervention to improve
      morbidity and psychosocial well-being in pupils with asthma. In all, 193 children
      with asthma (7-9 years) from 23 primary/junior schools in the south of England
      participated. Schools (n = 12) randomly assigned to the intervention group (IV)
      received a staff asthma training session, advice on asthma policy and practice
      and an emergency beta(2)-agonist inhaler with spacer. Pupils participated in an
      asthma lesson. Staff and pupils in non-intervention (NI) schools (n = 11)
      received no asthma-oriented input. While wheeze reports improved for all children
      with asthma, only the IV group showed lower requirement for medication (P =
      0.01), clinically significant improvement (P < 0.05) in activity related quality
      of life (QOL) and increased self-esteem (SE: social P = 0.01; athletic P = 0.05;
      behaviour P = 0.001) in girls. SE decreased for NI girls but there was no change
      for non-asthmatic peers in NI or IV schools which had similar baseline levels of
      SE and QOL. There was a marginal improvement in the establishment of asthma
      policies/practices and no change in school absence or staff knowledge. The
      significantly increased peer group understanding of asthma seen in the
      intervention schools may have mediated increased well-being in the IV group.
      Primary schools are a potentially important context for improving asthma
      morbidity and psychosocial well-being of children with asthma.

PMID- 18325912
TI  - A clinical study assessing the tolerability and biological effects of infliximab,
      a TNF-alpha inhibitor, in patients with advanced cancer.
AB  - BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) is an important regulator of
      the chronic inflammation contributing to tumour progression. Infliximab, an anti
      TNF-alpha monoclonal antibody was investigated in this trial of patients with
      advanced cancer. The primary objectives were to determine the safety profile and
      biological response of infliximab in a cancer population. Clinical response was a
      secondary objective. PATIENTS AND METHODS: Forty-one patients received infliximab
      at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4
      weeks. Post-treatment samples were measured for changes in plasma and serum TNF
      alpha, CCL2, IL-6 and C-reactive protein (CRP). RESULTS: Infliximab was well
      tolerated with no dose-limiting toxic effects. At both doses of infliximab,
      neutralisation of serum TNF-alpha was observed after 1 h while plasma CCL2, IL-6
      and serum CRP were decreased 24 and 48 h following infliximab administration.
      Seven patients experienced disease stablisation (range 10-50+ weeks). There was
      no evidence of disease acceleration in any patient. CONCLUSIONS: Infliximab
      treatment was safe and well tolerated in patients with advanced cancer. There was
      evidence of biological activity with baseline TNF-alpha and CCL2 being correlated
      with infliximab response.

PMID- 18325914
TI  - Prolonged neutropenia after dose-dense chemotherapy with pegfilgrastim.

PMID- 18325915
TI  - A new approach on bullous pemphigoid therapy.

PMID- 18325916
TI  - Can dynamic contrast-enhanced MRI (DCE-MRI) predict tumor recurrence and lymph
      node status in patients with breast cancer?

PMID- 18325917
TI  - p53 status and efficacy of primary anthracyclines/alkylating agent-based regimen
      according to breast cancer molecular classes.
AB  - BACKGROUND: We hypothesized that, among molecular subclasses of breast cancer,
      p53 status may have a differential predictive value for the efficacy of
      anthracyclines/alkylating agents-based regimen. We analysed the efficacy of a
      preoperative combination between 5-fluorouracil, anthracyclines and
      cyclophosphamide according to both p53 status and molecular classification.
      PATIENTS AND METHODS: Oestrogen receptor (ER), progesterone receptor (PgR), human
      epidermal growth factor receptor 2 (HER2) expression and p53 status were
      determined by immunohistochemistry in 293 samples from two different centres. A
      logistic regression model was used for multivariate analysis of predictors for
      pathological complete response (pCR). RESULTS: p53 immunostaining (54%) was
      associated with high grade (P = 0.002) and ER negativity (P = 0.04). p53 was
      detected in 59% of triple-negative tumours (ER-/PgR-/HER2-, n = 120 patients). In
      the overall population, pCR (9.6%) was independently predicted by high tumour
      grade (P = 0.002) and ER/PgR/HER2 triple negativity (P = 0.0004), but not by p53
      status (P = 0.12). p53 immunostaining was associated with a trend for a higher
      rate of pCR in triple-negative tumours [relative risk (RR) = 2.5, 95% confidence
      interval (CI) = 0.8-7.5, P = 0.09], but not in non-triple-negative tumours (RR =
      0.73, 95% CI = 0.16-3.3, P = 0.69). CONCLUSION: p53 status may have a different
      predictive value for efficacy of anthracycline/alkylating agents-based regimen in
      each molecular subclass, a result which may explain the different results
      reported in literature.

PMID- 18325919
TI  - Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using
      a novel in situ quantitative method of protein expression.
AB  - BACKGROUND: Kallikreins, a subgroup of the serine protease enzyme family, are
      considered important prognostic biomarkers in cancer. Here, we sought to
      determine the prognostic value of kallikrein 7 (hk7) in ovarian cancer using a
      novel method of compartmentalized in situ protein analysis. PATIENTS AND METHODS:
      A tissue array composed of 150 advanced-stage ovarian cancers, uniformly treated
      with surgical debulking followed by platinum-paclitaxel (Taxol) combination
      chemotherapy, was constructed. For evaluation of kallikrein 7 protein expression,
      we used an immunofluorescence-based method of automated in situ quantitative
      measurement of protein analysis (AQUA). RESULTS: Mean follow-up time of the
      cohort was 34.35 months. One hundred and twenty eight of 150 cases had sufficient
      tissue for AQUA. In univariate survival analysis, low tumor hk7 expression was
      associated with better outcome for overall survival (OS) and disease-free
      survival in 3 years (P values 0.032 and 0.037, respectively). In multivariate
      survival analysis, adjusting for well-characterized prognostic variables, low
      tumor hk7 expression level was the most significant predictor variable for OS
      (95% confidence interval 0.125-0.729, P = 0.007). CONCLUSIONS: High tumor hk7
      protein expression is associated with inferior patient outcome in ovarian cancer.
      hk7 may represent a promising prognostic factor in ovarian cancer.

PMID- 18325920
TI  - Developing innovative models for North-South cooperation in clinical research-
      experience from the INDOX Cancer Research Network.

PMID- 18325921
TI  - Quantification of changes in breast cancer incidence and mortality since 1990 in
      35 countries with Caucasian-majority populations.
AB  - BACKGROUND: Since 1985 considerable changes have taken place in the early
      detection and treatment of breast cancer. We quantified breast cancer trends for
      35 countries with populations mainly of European ancestry. METHODS: Incidence
      data were extracted from cancer registries and mortality data from World Health
      Organization database. Overall percentage change from 1990 to 2002 was quantified
      for all ages and for three different age-groups (35-49, 50-69 and >/=70 years of
      age). RESULTS: The incidence percent change in women of all ages varied from 2.1%
      in Canada to 54.2% in Lithuania. Main increases in incidence were observed for
      women 50-69 years old, from 12.4% in Canada until 105.3% in Norway. Decreases in
      mortality of >20% were observed in nine countries. Mortality decreases were
      highest in women 35-49 years old and lowest in women >/=70 years. The magnitude
      of mortality decrease from 1990 to 2002 was not related to the mortality rate
      observed in 1990. CONCLUSIONS: While increases in breast cancer incidence mainly
      concerned women >/=50 years, decreases in mortality were more marked in women 35
      49 years old. Large disparities in changes in mortality rates probably reflect
      differences in detection of and management of breast cancer.

PMID- 18325918
TI  - Premenopausal endocrine-responsive early breast cancer: who receives
      chemotherapy?
AB  - BACKGROUND: The role of chemotherapy in addition to combined endocrine therapy
      for premenopausal women with endocrine-responsive early breast cancer remains an
      open question, yet trials designed to answer it have repeatedly failed to
      adequately accrue. The International Breast Cancer Study Group initiated two
      concurrent trials in this population: in Premenopausal Endocrine Responsive
      Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in
      Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with
      inadequate accrual; TEXT accrued rapidly. METHODS: From 2003 to 2006, 1317
      patients (890 with baseline data) were randomly assigned to receive ovarian
      function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in
      TEXT. We explore patient-related factors according to whether or not chemotherapy
      was given using descriptive statistics and classification and regression trees.
      RESULTS: Adjuvant chemotherapy was chosen for 64% of patients. Lymph node status
      was the predominant determinant of chemotherapy use (88% of node positive treated
      versus 46% of node negative). Geography, patient age, tumor size and grade were
      also determinants, but degree of receptor positivity and human epidermal growth
      factor receptor 2 status were not. CONCLUSIONS: The perceived estimation of
      increased risk of relapse is the primary determinant for using chemotherapy
      despite uncertainties regarding the degree of benefit it offers when added to
      combined endocrine therapy in this population.

PMID- 18325922
TI  - Comparative mapping of HKT genes in wheat, barley, and rice, key determinants of
      Na+ transport, and salt tolerance.
AB  - Salt tolerance of plants depends on HKT transporters (High-affinity K(+)
      Transporter), which mediate Na(+)-specific transport or Na(+)-K(+) co-transport.
      Gene sequences closely related to rice HKT genes were isolated from hexaploid
      bread wheat (Triticum aestivum) or barley (Hordeum vulgare) for genomic DNA
      southern hybridization analysis. HKT gene sequences were mapped on chromosomal
      arms of wheat and barley using wheat chromosome substitution lines and barley
      wheat chromosome addition lines. In addition, HKT gene members in the wild
      diploid wheat ancestors, T. monococcum (A(m) genome), T. urartu (A(u) genome),
      and Ae. tauschii (D(t) genome) were investigated. Variation in copy number for
      individual HKT gene members was observed between the barley, wheat, and rice
      genomes, and between the different wheat genomes. HKT2;1/2-like, HKT2;3/4-like,
      HKT1;1/2-like, HKT1;3-like, HKT1;4-like, and HKT1;5-like genes were mapped to the
      wheat-barley chromosome groups 7, 7, 2, 6, 2, and 4, respectively. Chromosomal
      regions containing HKT genes were syntenic between wheat and rice except for the
      chromosome regions containing the HKT1;5-like gene. Potential roles of HKT genes
      in Na(+) transport in rice, wheat, and barley are discussed. Determination of the
      chromosome locations of HKT genes provides a framework for future physiological
      and genetic studies investigating the relationships between HKT genes and salt
      tolerance in wheat and barley.

PMID- 18325923
TI  - Genetic diversity in cyanobacterial symbionts of thalloid bryophytes.
AB  - Two species of thalloid liverworts, Blasia pusilla and Cavicularia densa, form
      stable symbioses with nitrogen-fixing cyanobacteria. Both bryophytes promote the
      persistence of their cyanobacterial associations by producing specialized gemmae,
      which facilitate the simultaneous dispersal of the host and its nitrogen-fixing
      symbionts. Here the genetic diversity of cyanobacterial symbionts of Blasia and
      Cavicularia is examined. The results indicate that the primary symbionts of both
      bryophytes are closely related and belong to a specific group of symbiotic Nostoc
      strains. Related strains have previously been reported from hornworts and cycads,
      and from many terricolous cyanolichens. The evolutionary origins of all these
      symbioses may trace back to pre-Permian times. While the laboratory strain Nostoc
      punctiforme PCC 73102 has been widely used in experimental studies of bryophyte
      Nostoc associations, sequence-identical cyanobionts have not yet been identified
      from thalloid liverworts in the field.

PMID- 18325924
TI  - Rubisco gene expression in C4 plants.
AB  - In leaves of most C(4) plants, ribulose 1,5 bisphosphate carboxylase (Rubisco)
      accumulates only in bundle sheath (bs) cells that surround the vascular centres,
      and not in mesophyll (mp) cells. It has been shown previously that in the C(4)
      dicots amaranth and Flaveria bidentis, post-transcriptional control of mRNA
      translation and stability mediate the C(4) expression patterns of genes encoding
      the large and small Rubisco subunits (chloroplast rbcL and nuclear RbcS,
      respectively). Translational control appears to regulate bs cell-specific Rubisco
      gene expression during early dicot leaf development, while control of mRNA
      stability appears to mediate bs-specific accumulation of RbcS and rbcL
      transcripts in mature leaves. Post-transcriptional control is also involved in
      the regulation of Rubisco gene expression by light, and in response to
      photosynthetic activity. Transgenic and transient expression studies in F.
      bidentis provide direct evidence for post-transcriptional control of bs cell
      specific RbcS expression, which is mediated by the 5' and 3' untranslated regions
      (UTRs) of the mRNA. Comparisons of Rubisco gene expression in these dicots and in
      the monocot maize indicates possible commonalities in the regulation of RbcS and
      rbcL genes in these divergent C(4) species. Now that the role of post
      transcriptional regulation in C(4) gene expression has been established, it is
      likely that future studies of mRNA-protein interactions will address long
      standing questions about the establishment and maintenance of cell type
      specificity in these plants. Some of these regulatory mechanisms may have
      ancestral origins in C(3) species, through modification of pre-existing factors,
      or by the acquisition of novel C(4) processes.

PMID- 18325925
TI  - Using the alkaline comet assay in prognostic tests for male infertility and
      assisted reproductive technology outcomes.
AB  - Infertility affects one in six couples in Europe during their reproductive years
      with dysfunctional sperm being one of the most common causes. Conventional semen
      analysis has proven variable and lacking in prognostic value so, over the past
      decade, more useful molecular fertility biomarkers have been explored. Among the
      tests showing most promise are those measuring sperm DNA quality. Sperm DNA
      damage has been closely associated with numerous indicators of reproductive
      health, including, fertilization, embryo quality, implantation, spontaneous
      abortion and childhood diseases. It therefore has great potential as a prognostic
      test for assisted reproductive treatment (ART), when couples are presenting with
      male infertility. Unlike somatic cells, sperm have a unique tightly compacted
      chromatin structure. Our group has modified the alkaline comet assay for use with
      sperm. Sperm DNA also differs from somatic cells in its high susceptibility to
      oxidative damage; this is largely due to the presence of abundant polyunsaturated
      fatty acids acting as substrates for reactive oxygen species (ROS) and its lack
      of repair mechanisms. Consequently, the effects of ROS and antioxidant protection
      on sperm DNA fragmentation have been widely investigated. In this review, the
      relationship between actual sperm DNA damage as determined by the alkaline comet
      assay and potential DNA damage as measured by DNA adduct testing will also be
      examined and the potential of routine clinical practices such as cryopreservation
      and prolonged incubation to induce further DNA damage was investigated. Finally,
      the usefulness of sperm DNA tests as prognostic markers and in particular, the
      opportunities and challenges provided by DNA testing in male fertility
      determination will be discussed.

PMID- 18325926
TI  - W-AlignACE: an improved Gibbs sampling algorithm based on more accurate position
      weight matrices learned from sequence and gene expression/ChIP-chip data.
AB  - MOTIVATION: Position weight matrices (PWMs) are widely used to depict the DNA
      binding preferences of transcription factors (TFs) in computational molecular
      biology and regulatory genomics. Thus, learning an accurate PWM to characterize
      the binding sites of a specific TF is a fundamental problem that plays an
      important role in modeling regulatory motifs and also in discovering the
      regulatory targets of TFs. RESULTS: We study the question of how to learn a more
      accurate PWM from both binding sequences and gene expression (or ChIP-chip) data,
      and propose to find a PWM such that the likelihood of simultaneously observing
      both binding sequences and their associated gene expression (or ChIP-chip) data
      is maximised. To solve the above maximum likelihood problem, a sequence weighting
      scheme is thus introduced based on the observation that binding sites inducing
      drastic fold changes in mRNA expression (or showing strong binding ratios in ChIP
      experiments) are likely to represent a true motif. We have incorporated this new
      learning approach into the popular motif finding program AlignACE. The modified
      program, called W-AlignACE, is compared with three other programs (AlignACE,
      MDscan and MotifRegressor) on a variety of datasets, including simulated data,
      mRNA expression and ChIP-chip data. These tests demonstrate that W-AlignACE is an
      effective tool for discovering TF binding motifs from gene expression (or ChIP
      chip) data and, in particular, has the ability to find very weak motifs like DIG1
      and GAL4. AVAILABILITY: http://www.ntu.edu.sg/home/ChenXin/Gibbs

PMID- 18325927
TI  - Merging two gene-expression studies via cross-platform normalization.
AB  - MOTIVATION: Gene-expression microarrays are currently being applied in a variety
      of biomedical applications. This article considers the problem of how to merge
      datasets arising from different gene-expression studies of a common organism and
      phenotype. Of particular interest is how to merge data from different
      technological platforms. RESULTS: The article makes two contributions to the
      problem. The first is a simple cross-study normalization method, which is based
      on linked gene/sample clustering of the given datasets. The second is the
      introduction and description of several general validation measures that can be
      used to assess and compare cross-study normalization methods. The proposed
      normalization method is applied to three existing breast cancer datasets, and is
      compared to several competing normalization methods using the proposed validation
      measures. AVAILABILITY: The supplementary materials and XPN Matlab code are
      publicly available at website: https://genome.unc.edu/xpn

PMID- 18325928
TI  - Relative contribution of mutations in genes for autosomal dominant distal
      hereditary motor neuropathies: a genotype-phenotype correlation study.
AB  - Distal hereditary motor neuropathy (HMN) is a clinically and genetically
      heterogeneous group of disorders affecting spinal alpha-motor neurons. Since
      2001, mutations in six different genes have been identified for autosomal
      dominant distal HMN; glycyl-tRNA synthetase (GARS), dynactin 1 (DCTN1), small
      heat shock 27 kDa protein 1 (HSPB1), small heat shock 22 kDa protein 8 (HSPB8),
      Berardinelli-Seip congenital lipodystrophy (BSCL2) and senataxin (SETX). In
      addition a mutation in the (VAMP)-associated protein B and C (VAPB) was found in
      several Brazilian families with complex and atypical forms of autosomal
      dominantly inherited motor neuron disease. We have investigated the distribution
      of mutations in these seven genes in a cohort of 112 familial and isolated
      patients with a diagnosis of distal motor neuropathy and found nine different
      disease-causing mutations in HSPB8, HSPB1, BSCL2 and SETX in 17 patients of whom
      10 have been previously reported. No mutations were found in GARS, DCTN1 and
      VAPB. The phenotypic features of patients with mutations in HSPB8, HSPB1, BSCL2
      and SETX fit within the distal HMN classification, with only one exception; a C
      terminal HSPB1-mutation was associated with upper motor neuron signs.
      Furthermore, we provide evidence for a genetic mosaicism in transmitting an HSPB1
      mutation. This study, performed in a large cohort of familial and isolated distal
      HMN patients, clearly confirms the genetic and phenotypic heterogeneity of distal
      HMN and provides a basis for the development of algorithms for diagnostic
      mutation screening in this group of disorders.

PMID- 18325930
TI  - Internal dosimetry verification and validation database.
AB  - Simulated-data internal dosimetry cases for use in intercomparison exercises or
      as a software verification and validation tool have been published on the
      internet (www.lanl.gov/bayesian/software Bayesian software package II). A user
      may validate their internal dosimetry code or method using this simulated
      bioassay data. Or, the user may choose to try out the Los Alamos National
      Laboratory codes ID and UF, which are also supplied. A Poisson-lognormal model of
      data uncertainty is assumed. A collection of different possible models for each
      nuclide (e.g. solubility types and particle sizes) are used. For example, for
      238Pu, 14 different biokinetic models or types (8 inhalation, 4 wound and 2
      ingestion) are assumed. Simulated data are generated for all the assumed
      biokinetic models, both for incidents, where the time of intake is known, and for
      non-incidents, where it is not. For the dose calculations, the route of intake,
      but not the biokinetic model, is considered to be known. The object is to
      correctly calculate the known true dose from simulated data covering a period of
      time. A 'correct' result has been defined in two ways: (1) that the credible
      limits of the calculated dose include the correct dose and (2) that the
      calculated dose is within a factor of 2 of the correct dose.

PMID- 18325929
TI  - Altered endothelin receptor binding in response to nitric oxide synthase
      inhibition in the pregnant rat.
AB  - The authors evaluate the expression of endothelin-1 (ET-1) and its receptors in
      the uterus and placenta during maternal nitric oxide synthase (NOS) inhibition.
      Timed-pregnant rats received L-NAME (2.5 mg/kg/h) or saline from day 14 to 21 of
      gestation. Uterine and placental tissues collected on day 21 were assayed for
      preproET-1, ET( A), and ET(B) mRNA expression; localization and expression of ET
      1 and receptor proteins; and receptor activity. NOS inhibition did not affect
      preproET-1 mRNA expression in the placenta or uterus. ET(A) expression decreased
      in the uterine free wall, but no other changes in receptor mRNA expression were
      observed in the uterus or placenta. ET-1 and receptor proteins were unchanged.
      Placental ET(A) and ET(B) receptor binding decreased. Uterine ET(A) receptor
      binding decreased in the placental bed. ET-1, a prominent mediator during NOS
      inhibition, is not of uterine or placental origin. Reduced receptor binding
      activity is the primary means by which these tissues regulate their response to
      ET-1 in the setting of NOS inhibition.

PMID- 18325931
TI  - On the need for quality assurance in superficial kilovoltage radiotherapy.
AB  - External auditing of beam output and energy qualities of four therapeutic X-ray
      machines were performed in three radiation oncology centres in northeastern
      Brazil. The output and half-value layers (HVLs) were determined using a parallel
      plate ionisation chamber and high-purity aluminium foils, respectively. The
      obtained values of absorbed dose to water and energy qualities were compared with
      those obtained by the respective institutions. The impact on the prescribed dose
      was analysed by determining the half-value depth (D(1/2)). The beam outputs
      presented percent differences ranging from -13 to +25%. The ratio between the HVL
      in use by the institution and the measurements obtained in this study ranged from
      0.75 to 2.33. Such deviations in HVL result in percent differences in dose at
      D(1/2) ranging from -52 to +8%. It was concluded that dosimetric quality audit
      programmes in radiation therapy should be expanded to include dermatological
      radiation therapy and such audits should include HVL verification.

PMID- 18325932
TI  - The depth-dependence of the biological effectiveness of 60Co gamma rays in a
      large absorber determined by dicentric chromosomes in human lymphocytes.
AB  - Radiobiological evidence is shown concerning a significant depth-dependence of
      the maximum relative biological effectiveness at limiting low doses (RBE(M)) of
      (60)Co gamma rays in a cubic polymethylmethacrylate (PMMA) phantom of 30 cm edge
      length. Using the dose-response curve for the dicentric data in human lymphocytes
      obtained in the present experiment at a depth of 20 cm, together with the
      comprehensive and consistent data set determined earlier at smaller depths of the
      PMMA phantom, there is an increase in the RBE(M) value by a factor of 2.18 +/-
      1.25 at a depth of 20 cm relative to 1 cm in the phantom. All the dicentric data
      are based on identical exposure durations and irradiation temperatures as well as
      identical culture and evaluation conditions, with blood from the same donor.

PMID- 18325933
TI  - Measurement of natural radioactivity in beach sands from Rizhao bathing beach,
      China.
AB  - The natural radioactivity of (226)Ra, (232)Th and (40)K was determined for beach
      sand samples collected from Rizhao bathing beach, China, using gamma ray
      spectrometry. The measured activity in beach sand ranges from 7.6 to 17.2, 7.8 to
      25.1 and 883.4 to 1313.6 Bq kg(-1) for (226)Ra, (232)Th and (40)K with mean
      values of 12.0, 15.2 and 1079.2 Bq kg(-1), respectively. The activity
      concentrations of (226)Ra and (232)Th in beach sands are lower, while (40)K is
      higher than the world average. The radium equivalent activity in all beach sand
      samples is lower than the safe limit set in the OECD report (370 Bq kg(-1)). The
      values of the external hazard index are less than unity. The mean outdoor air
      absorbed dose rate is 59.8 nGy h(-1) and the corresponding outdoor effective dose
      rate is 0.073 mSv y(-1).

PMID- 18325934
TI  - Comparative mutant analysis of Arabidopsis ABCC-type ABC transporters: AtMRP2
      contributes to detoxification, vacuolar organic anion transport and chlorophyll
      degradation.
AB  - The enormous metabolic plasticity of plants allows detoxification of many harmful
      compounds that are generated during biosynthetic processes or are present as
      biotic or abiotic toxins in their environment. Derivatives of toxic compounds
      such as glutathione conjugates are moved into the central vacuole via ATP-binding
      cassette (ABC)-type transporters of the multidrug resistance-associated protein
      (MRP) subfamily. The Arabidopsis genome contains 15 AtMRP isogenes, four of which
      (AtMRP1, 2, 11 and 12) cluster together in one of two major phylogenetic clades.
      We isolated T-DNA knockout alleles in all four highly homologous AtMRP genes of
      this clade and subjected them to physiological analysis to assess the function of
      each AtMRP of this group. None of the single atmrp mutants displayed visible
      phenotypes under control conditions. In spite of the fact that AtMRP1 and AtMRP2
      had been described as efficient ATP-dependent organic anion transporters in
      heterologous expression experiments, the contribution of three of the AtMRP genes
      (1, 11 and 12) to detoxification is marginal. Only knockouts in AtMRP2 exhibited
      a reduced sensitivity towards 1-chloro-2,4-dinitrobenzene, but not towards other
      herbicides. AtMRP2 but not AtMRP1, 11 and 12 is involved in chlorophyll
      degradation since ethylene-treated rosettes of atmrp2 showed reduced senescence,
      and AtMRP2 expression is induced during senescence. This suggests that AtMRP2 is
      involved in vacuolar transport of chlorophyll catabolites. Vacuolar uptake
      studies demonstrated that transport of typical MRP substrates was reduced in
      atmrp2. We conclude that within clade I, only AtMRP2 contributes significantly to
      overall organic anion pump activity in vivo.

PMID- 18325935
TI  - The signaling role of extracellular ATP and its dependence on Ca2+ flux in
      elicitation of Salvia miltiorrhiza hairy root cultures.
AB  - The application of a polysaccharide elicitor from yeast extract, YE, to Salvia
      miltiorrhiza hairy root cultures induced transient release of ATP from the roots
      to the medium, leading to a dose-dependent increase in the extracellular ATP
      (eATP) level. The eATP level rose to a peak (about 6.5 nM with 100 mg l(-1) YE)
      at about 10 h after YE treatment, but dropped to the control level 6 h later. The
      elicitor-induced ATP release was dependent on membrane Ca2+ influx, and abolished
      by the Ca2+ chelator EGTA or the channel blocker La3+. The YE-induced H2O2
      production was strongly inhibited by reactive blue (RB), a specific inhibitor of
      membrane purinoceptors. On the other hand, the application of exogenous ATP at 10
      100 microM to the cultures also induced rapid and dose-dependent increases in
      H2O2 production and medium pH, both of which were effectively blocked by RB and
      EGTA. The non-hydrolyzable ATP analog ATPgammaS was as effective as ATP, but the
      hydrolyzed derivatives ADP or AMP were not so effective in inducing the pH and
      H2O2 increases. Our results suggest that ATP release is an early event and that
      eATP plays a signaling role in the elicitation of plant cell responses; Ca2+ is
      required for activation of the elicitor-induced ATP release and the eATP signal
      transduction. This is the first report on ATP release induced by a fungal
      elicitor and its involvement in the elicitor-induced responses in plant cells.

PMID- 18325938
TI  - Acupuncture with in vitro fertilisation.

PMID- 18325939
TI  - Funding for primary health care in developing countries.

PMID- 18325940
TI  - Assessing the ability to work.

PMID- 18325941
TI  - Unresponsive asthma: Don't forget mediastinal masses.

PMID- 18325942
TI  - Bloodstream infection: Bacteraemia service model of infection care.

PMID- 18325943
TI  - Bloodstream infection: Early treatment strategies in sepsis.

PMID- 18325944
TI  - Doctors' education: Sponsored medical tourism.

PMID- 18325945
TI  - Doctors' education: Conflicts are everywhere.

PMID- 18325946
TI  - Depression in adults: GPs are not so bad at diagnosis.

PMID- 18325947
TI  - Traumatic brain injury: Time of hospital presentation may be important.

PMID- 18325948
TI  - Australia's healthcare reform body is criticised for its narrow membership.

PMID- 18325949
TI  - European Commission looks into possible restrictive practices by drug companies.

PMID- 18325950
TI  - Congress asks for investigation of FDA resources and staffing.

PMID- 18325951
TI  - Pfizer ends advertisements featuring inventor of artificial heart.

PMID- 18325953
TI  - Building people's faces from stem cells may be possible in two decades.

PMID- 18325954
TI  - Healthcare Commission will publicise NHS trusts' levels of infection control.

PMID- 18325955
TI  - Number of deaths from cancers falls after 20 years of screening in England.

PMID- 18325956
TI  - New commission will look at non-medical ways to improve health of Americans.

PMID- 18325962
TI  - Maternal health target is unlikely to be met, MPs warn.

PMID- 18325963
TI  - "A modest thoughtfulness".

PMID- 18325964
TI  - Is the declaration of Alma Ata still relevant to primary health care?

PMID- 18325965
TI  - Commentary: Good, but not perfect.

PMID- 18325966
TI  - Degenerative aortic stenosis.

PMID- 18325967
TI  - Diagnosis and management of irritable bowel syndrome in adults in primary care:
      summary of NICE guidance.

PMID- 18325968
TI  - Commentary: Controversies in NICE guidance on irritable bowel syndrome.

PMID- 18325973
TI  - New insight into the mechanism by which acute physical exercise ameliorates
      insulin resistance.

PMID- 18325974
TI  - How does inflammation affect axonal excitability to mechanical stimulation of
      neurones in the rat pain pathway?

PMID- 18325975
TI  - Persistent pain: the contribution of Na(V)1.9.

PMID- 18325976
TI  - Physiological differences between neurons in layer 2 and layer 3 of primary
      visual cortex (V1) of alert macaque monkeys.
AB  - The physiological literature does not distinguish between the superficial layers
      2 and 3 of the primary visual cortex even though these two layers differ in their
      cytoarchitecture and anatomical connections. To distinguish layer 2 from layer 3,
      we have analysed the response characteristics of neurons recorded during
      microelectrode penetrations perpendicular to the cortical surface. Extracellular
      responses of single neurons to sweeping bars were recorded while macaque monkeys
      performed a fixation task. Data were analysed from penetrations where cells could
      be localized to specific depths in the cortex. Although the most superficial
      cells (depth, 145-371 microm; presumably layer 2) responded preferentially to
      particular stimulus orientations, they were less selective than cells encountered
      immediately beneath them (depth, 386-696 microm; presumably layer 3). Layer 2
      cells had smaller spikes, higher levels of ongoing activity, larger receptive
      field activating regions, and less finely tuned selectivity for stimulus
      orientation and length than layer 3 cells. Direction selectivity was found only
      in layer 3. These data suggest that layer 3 is involved in generating and
      transmitting precise, localized information about image features, while the
      lesser selectivity of layer 2 cells may participate in top-down influences from
      higher cortical areas, as well as modulatory influences from subcortical brain
      regions.

PMID- 18325977
TI  - Microvascular function and ageing L-arginine, tetrahydrobiopterin and the search
      for the fountain of vascular youth.

PMID- 18325978
TI  - Repeated inspiratory occlusions acutely impair myocardial function in rats.
AB  - Repeated episodes of hypoxia and sympathetic activation during obstructive sleep
      apnoea are implicated in the initiation and progression of cardiovascular
      diseases, but the acute effects are unknown. We hypothesized that repeated
      inspiratory occlusions cause acute myocardial dysfunction and injury. In 22
      spontaneously breathing pentobarbital-anaesthetized rats, inspiration was
      occluded for 30 s every 2 min for 3 h. After approximately 1.5 h, mean arterial
      pressure started to fall; heart rate between occlusions was stable throughout,
      consistent with only transient increases in sympathetic activity during each
      occlusion. Three hours of occlusions resulted in ventricular diastolic
      dysfunction (reduced peak rate of change of ventricular pressure and slower
      relaxation). Post-occlusions, the left ventricular contractile response to
      dobutamine was blunted. After 1 h of recovery, left ventricular pressure
      generation had returned to values no different from those in sham animals in 5 of
      9 of the animals. Cardiac myofibrils from rats subjected to occlusions had
      depressed calcium-activated myosin ATPase activity, indicating myofilament
      contractile dysfunction that was not due to breakdown of contractile proteins.
      Haematoxylin and eosin-stained cross-sections revealed multifocal areas of
      necrosis within the septum and both ventricles. Repeated inspiratory occlusions,
      analogous to moderately severe obstructive sleep apnoea, acutely cause global
      cardiac dysfunction with multifocal myocardial infarcts.

PMID- 18325979
TI  - Role of leptin in the regulation of growth and carbohydrate metabolism in the
      ovine fetus during late gestation.
AB  - Leptin is an important regulator of appetite and energy expenditure in adulthood,
      although its role as a nutritional signal in the control of growth and metabolism
      before birth is poorly understood. This study investigated the effects of leptin
      on growth, carbohydrate metabolism and insulin signalling in fetal sheep. Crown
      rump length-measuring devices and vascular catheters were implanted in 12 sheep
      fetuses at 105-110 days of gestation (term 145 +/- 2 days). The fetuses were
      infused i.v. either with saline (0.9% NaCl; n = 6) or recombinant ovine leptin
      (0.5-1.0 mg kg(-1) day(-1); n = 6) for 5 days from 125 to 130 days when they were
      humanely killed and tissues collected. Leptin receptor mRNA and protein were
      expressed in fetal liver, skeletal muscle and perirenal adipose tissue.
      Throughout infusion, plasma leptin in the leptin-infused fetuses was 3- to 5-fold
      higher than in the saline-infused fetuses, although plasma concentrations of
      insulin, glucose, lactate, cortisol, catecholamines and thyroid hormones did not
      differ between the groups. Leptin infusion did not affect linear skeletal growth
      or body, placental and organ weights in utero. Hepatic glycogen content and
      activities of the gluconeogenic enzymes glucose-6-phosphatase and
      phosphoenolpyruvate carboxykinase in the leptin-infused fetuses were lower than
      in the saline-infused fetuses by 44, 48 and 36%, respectively; however, there
      were no differences in hepatic glycogen synthase activity or insulin signalling
      protein levels. Therefore, before birth, leptin may inhibit endogenous glucose
      production by the fetal liver when adipose energy stores and transplacental
      nutrient delivery are sufficient for the metabolic needs of the fetus. These
      actions of leptin in utero may contribute to the development of neonatal
      hypoglycaemia in macrosomic babies of diabetic mothers.

PMID- 18325980
TI  - Obestatin inhibits motor activity in the antrum and duodenum in the fed state of
      conscious rats.
AB  - Obestatin is a novel peptide encoded by the ghrelin precursor gene; however, its
      effects on gastrointestinal motility remain controversial. Here we have examined
      the effects of obestatin on fed and fasted motor activities in the stomach and
      duodenum of freely moving conscious rats. We examined the effects of intravenous
      (IV) injection of obestatin on the percentage motor index (%MI) and phase III
      like contractions in the antrum and duodenum. The brain mechanism mediating the
      action of obestatin on gastroduodenal motility and the involvement of vagal
      afferent pathway were also examined. Between 30 and 90 min after IV injection,
      obestatin decreased the %MI in the antrum and prolonged the time taken to return
      to fasted motility in the duodenum in fed rats given 3 g of chow after 18 h of
      fasting. Immunohistochemical analysis demonstrated that corticotropin-releasing
      factor- and urocortin-2-containing neurons in the paraventricular nucleus in the
      hypothalamus were activated by IV injection of obestatin. Intracerebroventricular
      injection of CRF type 1 and type 2 receptor antagonists prevented the effects of
      obestatin on gastroduodenal motility. Capsaicin treatment blocked the effects of
      obestatin on duodenal motility but not on antral motility. Obestatin failed to
      antagonize ghrelin-induced stimulation of gastroduodenal motility. These results
      suggest that, in the fed state, obestatin inhibits motor activity in the antrum
      and duodenum and that CRF type 1 and type 2 receptors in the brain might be
      involved in these effects of obestatin on gastroduodenal motility.

PMID- 18325981
TI  - Differential mechanisms of hepatic vascular dysregulation with mild vs. moderate
      ischemia-reperfusion.
AB  - Endotoxemia produces hepatic vascular dysregulation resulting from inhibition of
      endothelin (ET)-stimulated NO production. Mechanisms include overexpression of
      caveolin-1 (Cav-1) and altered phosphorylation of endothelial nitric oxide (NO)
      synthase (NOS; eNOS) in sinusoidal endothelial cells. Since ischemia-reperfusion
      (I/R) also causes vascular dysregulation, we tested whether the mechanisms are
      the same. Rats were exposed to either mild (30 min) or moderate (60 min) hepatic
      ischemia in vivo followed by reperfusion (6 h). Livers were harvested and
      prepared into precision-cut liver slices for in vitro analysis of NOS activity
      and regulation. Both I/R injuries significantly abrogated both the ET-1 (1
      microM) and the ET(B) receptor agonist (IRL-1620, 0.5 microM)-mediated
      stimulation of NOS activity. 30 min I/R resulted in overexpression of Cav-1 and
      loss of ET-stimulated phosphorylation of Ser1177 on eNOS, consistent with an
      inflammatory response. Sixty-minute I/R also resulted in loss of ET-stimulated
      Ser1177 phosphorylation, but Cav-1 expression was not altered. Moreover,
      expression of ET(B) receptors was significantly decreased. This suggests that the
      failure of ET to activate eNOS following 60-min I/R is associated with decreased
      protein expression consistent with ischemic injury. Thus hepatic vascular
      dysregulation following I/R is mediated by inflammatory mechanisms with mild I/R
      whereas ischemic mechanisms dominate following more severe I/R stress.

PMID- 18325982
TI  - Constitutive nitric oxide differentially regulates Na-H and Na-glucose
      cotransport in intestinal epithelial cells.
AB  - Previous in vivo studies suggest that constitutive nitric oxide (cNO) can
      regulate Na- glucose cotransport (SGLT1) and Na-H exchange (NHE3) in rabbit
      intestinal villus cells. Whether these two primary Na absorbing pathways are
      directly regulated by cNO and the mechanisms of this regulation in the enterocyte
      is not known. Thus nontransformed rat small intestinal epithelial cells (IEC-18)
      were treated with N(G)-nitro-l-arginine methyl ester (l-NAME), which directly
      decreased cNO in these cells. l-NAME treatment decreased SGLT1 in IEC-18 cells.
      Kinetic studies demonstrated that the mechanism of inhibition was secondary to a
      decrease in the affinity of the cotransporter for glucose without a change in the
      number of cotransporters. In contrast, l-NAME treatment increased NHE3 in IEC-18
      cells. Kinetic studies demonstrated that the mechanism of stimulation was by
      increasing the number of the exchangers without a change in the affinity for Na.
      Quantitative RT-PCR (RTQ-PCR) and Western blot analysis of SGLT1 demonstrated no
      change in mRNA and protein, respectively. RTQ-PCR and Western blot analysis of
      NHE3 indicated that NHE3 was increased by l-NAME treatment by an increase in mRNA
      and protein, respectively. These results indicate that decreased cNO levels
      directly mediate the inhibition of SGLT1 and stimulation of NHE3 in intestinal
      epithelial cells. Thus cNO directly but uniquely regulates the two primary Na
      absorptive pathways in the mammalian small intestine.

PMID- 18325983
TI  - Contribution of the sympathetic hormone epinephrine to the sensitizing effect of
      ethanol on LPS-induced liver damage in mice.
AB  - It is well known that ethanol preexposure sensitizes the liver to LPS
      hepatotoxicity. The mechanisms by which ethanol enhances LPS-induced liver injury
      are not completely elucidated but are known to involve an enhanced inflammatory
      response. Ethanol exposure also increases the metabolic rate of the liver, and
      this effect of ethanol on liver is mediated, at least in part, by the sympathetic
      hormone, epinephrine. However, whether or not the sympathetic nervous system also
      contributes to the sensitizing effect of ethanol preexposure on LPS-induced liver
      damage has not been determined. The purpose of this study was therefore to test
      the hypotheses that 1) epinephrine preexposure enhances LPS-induced liver damage
      (comparable to that of ethanol preexposure) and that 2) the sympathetic nervous
      system contributes to the sensitizing effect of ethanol. Accordingly, male
      C57BL/6J mice were administered epinephrine for 5 days (2 mg/kg per day) via
      osmotic pumps or bolus ethanol for 3 days (6 g/kg per day) by gavage. Twenty-four
      hours later, mice were injected with LPS (10 mg/kg ip). Both epinephrine and
      ethanol preexposure exacerbated LPS-induced liver damage and inflammation.
      Concomitant administration of propranolol with ethanol significantly attenuated
      the sensitizing effect of ethanol on LPS-induced liver damage. These data support
      the hypothesis that the sympathetic nervous system contributes, at least in part,
      to the mechanism of the sensitizing effect of ethanol. These results also suggest
      that sympathetic tone may contribute to the initiation and progression of
      alcoholic liver disease.

PMID- 18325984
TI  - CUGBP2 downregulation by prostaglandin E2 protects colon cancer cells from
      radiation-induced mitotic catastrophe.
AB  - Prostaglandin E(2) (PGE(2)) is a potent inhibitor of ionizing radiation (IR)
      induced cell death. Exposure of colon cancer cells to IR leads to increased
      CUGBP2 expression. Therefore, we tested the hypothesis that PGE(2) radioprotects
      colon cancer cells by inhibiting CUGBP2 expression. Exposure of HCT-116 cells to
      gamma-IR (0-12 Gy) resulted in a dose-dependent reduction in cell growth and an
      increase in the G(2)-M phase of the cell cycle. Western blot analyses
      demonstrated increased levels of activated caspase 9 and caspase 3. In addition,
      whereas Bax expression is increased, that of Bcl-2 and Bcl-x(L) was reduced.
      Further analyses demonstrated increased activation of Chk1 and Chk2 kinases,
      coupled with higher levels of nuclear cyclin B1 and Cdc2. Pretreatment with
      PGE(2) suppressed the activation of caspase 3 and caspase 7 and inhibited Bax
      expression. In addition, PGE(2) treatment restored growth and colony formation to
      control levels. IR significantly upregulated the expression of CUGBP2 in the
      cells, which was suppressed when cells were pretreated with PGE(2). Ectopic
      overexpression of CUGBP2 also induced apoptosis. Furthermore, it reversed the
      PGE(2)-mediated protection from IR-induced mitotic catastrophe. Furthermore,
      there was an increase in nuclear localization of cyclin B1 and Cdc2 coupled with
      increased phosphorylation of p53, Chk1, Chk2, and Cdc25c proteins. Cell cycle
      analysis also demonstrated increased G(2)-M transition. In contrast, siRNA
      mediated suppression of CUGBP2 expression restored normal cell cycle progression
      and decreased IR-induced apoptosis. Taken together, these data demonstrate that
      PGE(2) protects colon cancer cells from IR-induced mitotic catastrophe in part
      through suppression of CUGBP2 expression.

PMID- 18325985
TI  - Transient receptor potential vanilloid 4 mediates protease activated receptor 2
      induced sensitization of colonic afferent nerves and visceral hyperalgesia.
AB  - Protease-activated receptor (PAR(2)) is expressed by nociceptive neurons and
      activated during inflammation by proteases from mast cells, the intestinal lumen,
      and the circulation. Agonists of PAR(2) cause hyperexcitability of intestinal
      sensory neurons and hyperalgesia to distensive stimuli by unknown mechanisms. We
      evaluated the role of the transient receptor potential vanilloid 4 (TRPV4) in
      PAR(2)-induced mechanical hyperalgesia of the mouse colon. Colonic sensory
      neurons, identified by retrograde tracing, expressed immunoreactive TRPV4,
      PAR(2), and calcitonin gene-related peptide and are thus implicated in
      nociception. To assess nociception, visceromotor responses (VMR) to colorectal
      distension (CRD) were measured by electromyography of abdominal muscles. In
      TRPV4(+/+) mice, intraluminal PAR(2) activating peptide (PAR(2)-AP) exacerbated
      VMR to graded CRD from 6-24 h, indicative of mechanical hyperalgesia. PAR(2)
      induced hyperalgesia was not observed in TRPV4(-/-) mice. PAR(2)-AP evoked
      discharge of action potentials from colonic afferent neurons in TRPV4(+/+) mice,
      but not from TRPV4(-/-) mice. The TRPV4 agonists 5',6'-epoxyeicosatrienoic acid
      and 4alpha-phorbol 12,13-didecanoate stimulated discharge of action potentials in
      colonic afferent fibers and enhanced current responses recorded from retrogradely
      labeled colonic dorsal root ganglia neurons, confirming expression of functional
      TRPV4. PAR(2)-AP enhanced these responses, indicating sensitization of TRPV4.
      Thus TRPV4 is expressed by primary spinal afferent neurons innervating the colon.
      Activation of PAR(2) increases currents in these neurons, evokes discharge of
      action potentials from colonic afferent fibers, and induces mechanical
      hyperalgesia. These responses require the presence of functional TRPV4.
      Therefore, TRPV4 is required for PAR(2)-induced mechanical hyperalgesia and
      excitation of colonic afferent neurons.

PMID- 18325986
TI  - Hypermetabolic syndrome as a consequence of repeated psychological stress in
      mice.
AB  - Stress is a powerful modulator of neuroendocrine, behavioral, and immunological
      functions. After 4.5-d repeated combined acoustic and restraint stress as a
      murine model of chronic psychological stress, severe metabolic dysregulations
      became detectable in female BALB/c mice. Stress-induced alterations of metabolic
      processes that were found in a hepatic mRNA expression profiling were verified by
      in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome
      with the severe loss of lean body mass, hyperglycemia, dyslipidemia, increased
      amino acid turnover, and acidosis. This was associated with hypercortisolism,
      hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a
      single acute stress exposure, changes in expression of metabolic genes were much
      less pronounced and predominantly confined to gluconeogenesis, probably
      indicating that metabolic disturbances might be initiated already early but will
      only manifest in repeatedly stressed mice. Thus, in our murine model, repeated
      stress caused severe metabolic dysregulations, leading to a drastic reduction of
      the individual's energy reserves. Under such circumstances stress may further
      reduce the ability to cope with new stressors such as infection or cancer.

PMID- 18325987
TI  - Systemic and distal repercussions of liver-specific peroxisome proliferator
      activated receptor-alpha control of the acute-phase response.
AB  - The acute-phase response is characterized by the modulation of liver expression
      of many proteins involved in a diversity of biological functions. Among them,
      some are associated with the pathology of atherosclerosis. We previously found
      that peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists
      attenuate the IL-6 induction of acute-phase response gene expression in vitro and
      in vivo. In the current work, we found a PPARalpha-dependent regulation of
      hepatic acute-phase response stimulated by IL-1. We also found that IL-1
      stimulated expression of secondary wave cytokines such as IL-6 is prevented upon
      PPARalpha activation in liver. Direct involvement of hepatic PPARalpha was
      demonstrated using a liver-restricted expression of PPARalpha in mice. IL-1- or
      IL-6-mediated acute-phase response was inhibited by fenofibrate treatment in
      liver-specific PPARalpha-expressing mice but not in PPARalpha-deficient mice. In
      addition, we demonstrated that PPARalpha exerts a general control of the acute
      phase response by using an inflammation/infection model of lipopolysaccharide. In
      such a context, liver-specific PPARalpha-expressing mice displayed lower
      circulating levels of TNF, IL-1, and IL-6 cytokines. We found a distal
      repercussion of this lowering at the vascular wall level as illustrated by a
      decreased expression of adhesion molecules in aorta. In conclusion, we
      demonstrated that through a specific liver action, PPARalpha behaves as a
      modulator of systemic inflammation and of the associated vascular response.

PMID- 18325988
TI  - Intracellular proadrenomedullin-derived peptides decorate the microtubules and
      contribute to cytoskeleton function.
AB  - Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are
      secretory hormones, but it is not unusual to find them in intracellular
      compartments. Using yeast-2 hybrid technology, we found interactions between AM
      and several microtubule-associated proteins (MAPs), and between PAMP and tubulin.
      Expression of fluorescent-tagged AM and PAMP as well as immunofluorescence for
      the native peptides showed a complete decoration of the microtubules and
      colocalization with other MAPs. PAMP, but not AM, bound to tubulin in vitro and
      destabilized tubulin polymerization. Down-regulation of the gene coding for both
      AM and PAMP through small interfering RNA technology resulted in morphological
      changes, microtubule stabilization, increase in posttranslational modifications
      of tubulin such as acetylation and detyrosination, reduction in cell motility,
      and partial arrest at the G2 phase of the cell cycle, when compared with cells
      transfected with the same vector carrying a scrambled sequence. These results
      show that PAMP is a novel MAP, whereas AM may be exerting more subtle effects in
      regulating cytoskeleton function.

PMID- 18325989
TI  - Role for inhibitor of differentiation/deoxyribonucleic acid-binding (Id) proteins
      in granulosa cell differentiation.
AB  - Recent studies in the hen ovary have linked the initiation of granulosa cell
      differentiation at follicle selection to the alleviation of inhibitory MAPK
      signaling. The present studies assessed a role for individual inhibitor of
      differentiation (Id) protein isoforms as modulators of key transcriptional events
      occurring within granulosa cells at or immediately subsequent to differentiation.
      Findings from freshly collected granulosa cells collected at different stages of
      follicle development demonstrated a negative association between expression
      levels for Id2 mRNA compared with levels of Id1, Id3, and Id4. Elevated levels of
      Id2 are related to a differentiating/differentiated phenotype, whereas elevated
      Id1, Id3, and Id4 are associated with an undifferentiated phenotype. This
      negative relationship extends to cell signal transduction, because factors that
      promote inhibitory MAPK signaling (TGF-alpha and betacellulin) block expression
      of Id2 mRNA but increase levels of Id1, Id3, and Id4. Furthermore, overexpression
      of Gallus Id2 in cultured granulosa was found to significantly decrease levels of
      Id1, Id3, and Id4 mRNA but facilitate FSHR mRNA expression and, importantly,
      initiate LHR mRNA expression plus LH-induced progesterone production. Finally,
      knockdown studies using small interfering RNA specific for Id2 revealed reduced
      expression of FSHR and LHR mRNA and attenuated FSH- and LH-induced levels of StAR
      and p450 cholesterol side-chain cleavage enzyme mRNA plus progesterone
      production. Collectively, these data demonstrate that Id2 expression is both
      sufficient and necessary for increasing LHR expression and, as a result,
      promoting gonadotropin-induced differentiation in hen granulosa cells subsequent
      to follicle selection.

PMID- 18325990
TI  - Active intestinal calcium transport in the absence of transient receptor
      potential vanilloid type 6 and calbindin-D9k.
AB  - To study the role of the epithelial calcium channel transient receptor potential
      vanilloid type 6 (TRPV6) and the calcium-binding protein calbindin-D9k in
      intestinal calcium absorption, TRPV6 knockout (KO), calbindin-D9k KO, and
      TRPV6/calbindin-D(9k) double-KO (DKO) mice were generated. TRPV6 KO, calbindin
      D9k KO, and TRPV6/calbindin-D9k DKO mice have serum calcium levels similar to
      those of wild-type (WT) mice ( approximately 10 mg Ca2+/dl). In the TRPV6 KO and
      the DKO mice, however, there is a 1.8-fold increase in serum PTH levels (P < 0.05
      compared with WT). Active intestinal calcium transport was measured using the
      everted gut sac method. Under low dietary calcium conditions there was a 4.1-,
      2.9-, and 3.9-fold increase in calcium transport in the duodenum of WT, TRPV6 KO,
      and calbindin-D9k KO mice, respectively (n = 8-22 per group; P > 0.1, WT vs.
      calbindin-D9k KO, and P < 0.05, WT vs. TRPV6 KO on the low-calcium diet).
      Duodenal calcium transport was increased 2.1-fold in the TRPV6/calbindin-D9k DKO
      mice fed the low-calcium diet (P < 0.05, WT vs. DKO). Active calcium transport
      was not stimulated by low dietary calcium in the ileum of the WT or KO mice. 1,25
      Dihydroxyvitamin D3 administration to vitamin D-deficient null mutant and WT mice
      also resulted in a significant increase in duodenal calcium transport (1.4- to
      2.0-fold, P < 0.05 compared with vitamin D-deficient mice). This study provides
      evidence for the first time using null mutant mice that significant active
      intestinal calcium transport occurs in the absence of TRPV6 and calbindin-D9k,
      thus challenging the dogma that TRPV6 and calbindin-D9k are essential for vitamin
      D-induced active intestinal calcium transport.

PMID- 18325991
TI  - Hormonal regulation of suppressors of cytokine signaling (SOCS) messenger
      ribonucleic acid in the arcuate nucleus during late pregnancy.
AB  - Prolactin stimulates tuberoinfundibular dopamine neurons in the arcuate nucleus
      of the hypothalamus, mediated by signal transducer and activator of transcription
      5b (STAT5b). During late pregnancy, these neurons become unresponsive to
      prolactin, with a loss of prolactin-induced activation of STAT5b and decreased
      dopamine secretion. Suppressors of cytokine signaling (SOCS) proteins inhibit
      STAT-mediated signaling, and SOCS mRNAs are specifically elevated in the arcuate
      nucleus during late pregnancy. We hypothesized that changes in circulating
      ovarian steroids during late pregnancy might induce expression of SOCS mRNAs,
      thus disrupting STAT5b-mediated prolactin signaling. Rats were ovariectomized on
      d 18 of pregnancy and treated with ovarian steroids to simulate an advanced,
      normal, or delayed decline in progesterone. Early progesterone withdrawal caused
      an early increase in prolactin secretion, and increased SOCS-1 and -3 and
      cytokine-inducible SH2-containing protein (CIS) mRNA levels in the arcuate
      nucleus. Prolonged progesterone treatment prevented these changes. To determine
      whether ovarian steroids directly alter SOCS mRNA levels, estrogen- and/or
      progesterone-treated ovariectomized nonpregnant rats were acutely injected with
      prolactin (300 microg sc) or vehicle. SOCS-1 and -3 and CIS mRNA levels in the
      arcuate nucleus were significantly increased by estrogen or prolactin, whereas
      progesterone treatment reversed the effect of estrogen. Results demonstrate that
      estrogen and prolactin can independently induce SOCS mRNA in the arcuate nucleus
      and that this effect is negatively regulated by progesterone. This is consistent
      with the hypothesis that declining progesterone and high levels of estrogen
      during late pregnancy induce SOCS in the tuberoinfundibular dopamine neurons,
      thus contributing to their insensitivity to prolactin at this time.

PMID- 18325992
TI  - Infertility in females with cystic fibrosis is multifactorial: evidence from
      mouse models.
AB  - Infertility is commonly associated with cystic fibrosis (CF). Although
      infertility in men with CF has been thoroughly investigated, the infertility
      observed in women with CF has not been well studied. To investigate female
      infertility associated with CF, we used two independently derived mouse models of
      CF. Both of these models displayed decreased fertility characterized by a
      reduction in litter number and litter size. Our findings suggest that much of the
      reduced fertility in these mice originates from decreased fertilization due to
      inadequate sperm transport within the female reproductive tract. However, our
      data indicate that additional reproductive phenotypes in the CF female mice also
      contribute to the reduced fertility including small ovarian and uterine size,
      aberrant estrous cycles, and decreased oocyte ovulation rates. These data, along
      with previous work demonstrating that the gene mutated in CF, the cystic fibrosis
      transmembrane conductance regulator (CFTR), is normally expressed in tissues
      vital to reproduction, raises the possibility that CFTR may have a direct effect
      on fertility. If so, CFTR may also play an important role in normal female
      fertility within the general population.

PMID- 18325993
TI  - Identification of an upstream promoter of the human somatostatin receptor,
      hSSTR2, which is controlled by epigenetic modifications.
AB  - Somatostatin is a neuropeptide that inhibits exocrine and endocrine secretions of
      several hormones and negatively regulates cell proliferation. These events are
      mediated through somatostatin engagement on one of five G protein-coupled
      receptors named SSTR1 to STTR5. Somatostatin binding to SSTR2 mediates
      predominantly antisecretory and antiproliferative effects; two important
      biological activities in the gastroenteropancreatic endocrine and exocrine
      system. Herein we demonstrate novel regulatory sequences for human (h) SSTR2
      transcription. By genomic DNA sequence analysis, we reveal two CpG islands
      located 3.8 kb upstream from the transcription start site. We identify a novel
      transcription start site and a promoter region within one of these CpG islands.
      We demonstrate that two epigenetic modifications, DNA methylation and histone
      acetylation, regulate the activation of hSSTR2 upstream promoter. Furthermore, we
      show that the transcription from this upstream promoter region directly
      correlates to hSSTR2 mRNA expression in various human cell lines. A combined
      treatment of a demethylating agent, 5-aza-2-deoxycytidine and a histone
      deacetylase inhibitor, trichostatin A, leads to increased expression of hSSTR2
      mRNA in cell lines in which the CpG island is methylated. The epigenetic
      regulation of this promoter region results in differential expression of hSSTR2
      mRNA in human cell lines. This study reveals the existence of a novel upstream
      promoter for the hSSTR2 gene that is regulated by epigenetic modifications,
      suggesting for complex control of the hSSTR2 transcription.

PMID- 18325994
TI  - Involvement of cytokine-induced neutrophil chemoattractant in hypothalamic
      thermoregulation of luteinizing hormone-releasing hormone.
AB  - We demonstrated in a previous study that serum IL-8 concentrations were
      significantly higher in women with hot flashes than without hot flashes. To
      clarify the role of IL-8 in the pathoetiology of menopausal hot flashes, we
      examined the effect of rat cytokine-induced neutrophil chemoattractant (CINC), a
      member of the IL-8 family, on thermoregulation using ovariectomized (OVX) rats
      treated with intracerebroventricular (i.c.v.) injection of LHRH agonist (LHRHa)
      as a model of hot flashes. We found that: 1) expression of CINC mRNA was
      increased around the periventricular area in the hypothalamus at 1 h, and the
      serum CINC concentration was increased at 2 h after i.c.v. injection of LHRHa; 2)
      the increase in serum CINC concentration in hypophysectomized rats was
      significantly lower than that in sham-operated rats; 3) i.c.v. but not iv
      injection of CINC elevated the rectal temperature of OVX rats; 4) i.c.v.
      injection of LHRHa into OVX rats produced a rapid rise (maximal increase: 10-25
      min) in tail skin temperature, and the elevation was augmented by injection of an
      anti-CINC antibody; and 5) changes in serum CINC concentration and skin
      temperature after i.c.v. injection of LHRHa were reversed by replacement of
      estradiol. In conclusion, the production of CINC in the hypothalamus due to LHRHa
      injection in OVX rats was increased after elevation of skin temperature,
      suggesting that CINC plays a key role in the homeostasis of body temperature.
      Disturbance of the thermoregulatory mechanism involving LHRH and CINC may be
      related to the pathoetiology of hot flashes.

PMID- 18325995
TI  - Functional characterization of genetically labeled gonadotropes.
AB  - Gonadotropes are crucial in the control of reproduction but difficult to isolate
      for functional analysis due to their scattered distribution in the anterior
      pituitary gland. We devised a binary genetic approach, and describe a new mouse
      model that allows visualization and manipulation of gonadotrope cells. Using gene
      targeting in embryonic stem cells, we generated mice in which Cre recombinase is
      coexpressed with the GnRH receptor, which is expressed in gonadotrope cells. We
      show that we can direct Cre-mediated recombination of a yellow fluorescent
      protein reporter allele specifically in gonadotropes within the anterior
      pituitary of these knock-in mice. More than 99% of gonadotropin-containing cells
      were labeled by yellow fluorescent protein fluorescence and readily identifiable
      in dissociated pituitary cell culture, allowing potentially unbiased sampling
      from the gonadotrope population. Using electrophysiology, calcium imaging, and
      the study of secretion on the single-cell level, the functional properties of
      gonadotropes isolated from male mice were analyzed. Our studies demonstrate a
      significant heterogeneity in the resting properties of gonadotropes and their
      responses to GnRH. About 50% of gonadotropes do not exhibit secretion of LH or
      FSH. Application of GnRH induced a broad range of both electrophysiological
      responses and increases in the intracellular calcium concentration. Our mouse
      model will also be able to direct expression of other Cre recombination-dependent
      reporter genes to gonadotropes and, therefore, represents a versatile new tool in
      the understanding of gonadotrope biology.

PMID- 18325996
TI  - Adaptation to mild, intermittent stress delays development of hyperglycemia in
      the Zucker diabetic Fatty rat independent of food intake: role of habituation of
      the hypothalamic-pituitary-adrenal axis.
AB  - Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity occurs in type 2
      diabetes, and stress is assumed to play a causal role. However, intermittent
      restraint stress, a model mimicking some mild stressors, delays development of
      hyperglycemia in Zucker diabetic fatty (ZDF) rats. We examine whether such stress
      delays hyperglycemia independent of stress-induced reductions in hyperphagia and
      is due to adaptations in gene expression of HPA-related peptides and receptors
      that ameliorate corticosteronemia and thus hyperglycemia. ZDF rats were
      intermittently restraint stressed (1 h/d, 5 d/wk) for 13 wk and compared with
      obese control, pair fed, and lean ZDF rats. After 13 wk, basal hormones were
      repeatedly measured over 24 h, and HPA-related gene expression was assessed by in
      situ hybridization. Although restraint initially induced hyperglycemia, this
      response habituated over time, and intermittent restraint delayed hyperglycemia.
      This delay was partly related to 5-15% decreased hyperphagia, which was not
      accompanied by decreased arcuate nucleus NPY or increased POMC mRNA expression,
      although expression was altered by obesity. Obese rats demonstrated basal
      hypercorticosteronemia and greater corticosterone responses to food/water
      removal. Basal hypercorticosteronemia was further exacerbated after 13 wk of pair
      feeding during the nadir. Importantly, intermittent restraint further delayed
      hyperglycemia independent of food intake, because glycemia was 30-40% lower than
      after 13 wk of pair feeding. This may be mediated by increased hippocampal MR
      mRNA, reduced anterior pituitary POMC mRNA levels, and lower adrenal sensitivity
      to ACTH, thus preventing basal and stress-induced hypercorticosteronemia. In
      contrast, 24-h catecholamines were unaltered. Thus, rather than playing a causal
      role, intermittent stress delayed deteriorations in glycemia and ameliorated HPA
      hyperactivity in the ZDF rat.

PMID- 18325997
TI  - Differential regulation of prostaglandin production mediated by corticotropin
      releasing hormone receptor type 1 and type 2 in cultured human placental
      trophoblasts.
AB  - Prostaglandin (PG) production by intrauterine tissues plays a key part in the
      control of pregnancy and parturition. The present study was to investigate the
      role of placenta-derived CRH and CRH-related peptides in the regulation of PG
      synthesis and metabolism. We found that placental trophoblasts expressed both CRH
      R1 and CRH-R2. Treatment of cultured placental cells with either a CRH or
      urocortin I (UCNI) antibody resulted in a significant decrease in PGE2 release.
      Both CRH and UCNI antibodies significantly decreased mRNA and protein expression
      of synthetic enzymes cytosolic phospholipase A2 (cPLA2) and cyclooxygenase (COX)
      2 and increased mRNA and protein expression of 15-hydroxyprostaglandin
      dehydrogenase (PGDH), the key enzyme of PG metabolism. CRH-R1/-R2 antagonist
      astressin and CRH-R1 antagonist antalarmin significantly inhibited PGE2 release,
      whereas CRH-R2 antagonist astressin-2b had no effect on PGE(2) release.
      Administration of astressin decreased expression of cPLA2 but had no effect on
      COX-2 expression. Antalarmin reduced cPLA2 and COX-2 expression, whereas
      astressin-2b did not alter cPLA2 expression but increased COX-2 expression. PGDH
      expression was enhanced by these three antagonists. Cells treated with exogenous
      CRH and UCNI showed an increase in PGE(2) release and expression of cPLA2 and COX
      2 but a decrease in PGDH expression. UCNII and UCNIII had no effect on PGE2
      release but decreased COX-2 and PGDH expression. Our results suggested CRH and
      CRH-related peptides act on CRH-R1 and CRH-R2 to exert different effects on PG
      biosynthetic enzymes cPLA2 and COX-2 and thereby modulate output of PGs from
      placenta, which would be important for controlling pregnancy and parturition.

PMID- 18325998
TI  - Evidence that gamma-aminobutyric acid is part of the neural circuit mediating
      estradiol negative feedback in anestrous ewes.
AB  - Seasonal anestrus in ewes is driven by an increase in response to estradiol (E2)
      negative feedback. Compelling evidence indicates that inhibitory A15 dopaminergic
      (DA) neurons mediate the increased inhibitory actions of E2 in anestrus, but
      these neurons do not contain estrogen receptors. Therefore, we have proposed that
      estrogen-responsive afferents to A15 neurons are part of the neural circuit
      mediating E2 negative feedback in anestrus. This study examined the possible role
      of afferents containing gamma-aminobutyric acid (GABA) and nitric oxide (NO) in
      modulating the activity of A15 neurons. Local administration of NO synthase
      inhibitors to the A15 had no effect on LH, but GABA receptor ligands produced
      dramatic changes. Administration of either a GABA A or GABA B receptor agonist to
      the A15 increased LH secretion in ovary-intact ewes, suggesting that GABA
      inhibits A15 neural activity. In ovariectomized anestrous ewes, the same doses of
      GABA receptor agonist had no effect, but combined administration of a GABA A and
      GABA B receptor antagonist to the A15 inhibited LH secretion. These data are
      consistent with the hypothesis that endogenous GABA release within the A15 is low
      in ovary-intact anestrous ewes and elevated after ovariectomy. Using dual
      immunocytochemistry, we observed that GABAergic varicosities make close contacts
      on to A15 neurons and that A15 neurons contain both the GABA A-alpha1 and the
      GABA B-R1 receptor subunits. Based on these data, we propose that in anestrous
      ewes, E2 inhibits release of GABA from afferents to A15 DA neurons, increasing
      the activity of these DA neurons and thus suppressing episodic secretion of GnRH
      and LH.

PMID- 18325999
TI  - The orphan nuclear receptor, NOR-1, a target of beta-adrenergic signaling,
      regulates gene expression that controls oxidative metabolism in skeletal muscle.
AB  - beta 1-3-Adrenoreceptor (AR)-deficient mice are unable to regulate energy
      expenditure and develop diet-induced obesity on a high-fat diet. We determined
      previously that beta2-AR agonist treatment activated expression of the mRNA
      encoding the orphan nuclear receptor, NOR-1, in muscle cells and plantaris
      muscle. Here we show that beta2-AR agonist treatment significantly and
      transiently activated the expression of NOR-1 (and the other members of the NR4A
      subgroup) in slow-twitch oxidative soleus muscle and fast-twitch glycolytic
      tibialis anterior muscle. The activation induced by beta-adrenergic signaling is
      consistent with the involvement of protein kinase A, MAPK, and phosphorylation of
      cAMP response element-binding protein. Stable cell lines transfected with a
      silent interfering RNA targeting NOR-1 displayed decreased palmitate oxidation
      and lactate accumulation. In concordance with these observations, ATP production
      in the NOR-1 silent interfering RNA (but not control)-transfected cells was
      resistant to (azide-mediated) inhibition of oxidative metabolism and expressed
      significantly higher levels of hypoxia inducible factor-1alpha. In addition, we
      observed the repression of genes that promote fatty acid oxidation (peroxisomal
      proliferator-activated receptor-gamma coactivator-1alpha/beta and lipin-1alpha)
      and trichloroacetic acid cycle-mediated carbohydrate (pyruvate) oxidation
      [pyruvate dehydrogenase phosphatase 1 regulatory and catalytic subunits (pyruvate
      dehydrogenase phosphatases-1r and -c)]. Furthermore, we observed that beta2-AR
      agonist administration in mouse skeletal muscle induced the expression of genes
      that activate fatty acid oxidation and modulate pyruvate use, including PGC
      1alpha, lipin-1alpha, FOXO1, and PDK4. Finally, we demonstrate that NOR-1 is
      recruited to the lipin-1alpha and PDK-4 promoters, and this is consistent with
      NOR-1-mediated regulation of these genes. In conclusion, NOR-1 is necessary for
      oxidative metabolism in skeletal muscle.

PMID- 18326000
TI  - Vasoactive intestinal polypeptide can excite gonadotropin-releasing hormone
      neurons in a manner dependent on estradiol and gated by time of day.
AB  - A surge of GnRH release signals the LH surge that triggers ovulation. The GnRH
      surge is dependent on a switch in estradiol feedback from negative to positive
      and, in rodents, a daily neural signal, likely from the suprachiasmatic nuclei.
      Vasoactive intestinal polypeptide (VIP) may be involved in suprachiasmatic nuclei
      GnRH neuron communication. Here we assessed the effects of acute VIP (5 min
      treatment) on GnRH neuron function using targeted extracellular recordings of
      firing activity of GnRH neurons in brain slices. We examined the effect of VIP on
      firing rate at different times of day using an established ovariectomized,
      estradiol-treated (OVX+E) mouse model that exhibits daily LH surges timed to the
      late afternoon. Cells from OVX animals (no estradiol) did not respond to VIP,
      regardless of time of day. With estradiol, the effect of VIP on GnRH neurons was
      dependent on the time of recording. During negative feedback, OVX+E cells did not
      respond. VIP increased firing in cells recorded during surge onset, but this
      excitatory response was reduced at surge peak. Acute treatment of OVX+E cells
      during surge peak with a VIP receptor antagonist decreased GnRH neuron firing.
      This suggests endogenous VIP may both increase GnRH neuron firing during the
      surge and occlude response to exogenous VIP. These data provide functional
      evidence for VIP effects on GnRH neurons and indicate that both estradiol and
      time of day gate the GnRH neuron response to this peptide. VIP may provide an
      excitatory signal from the circadian clock that helps time the GnRH surge.

PMID- 18326001
TI  - Angiotensin II type 2 receptor stimulation increases the rate of NG108-15 cell
      migration via actin depolymerization.
AB  - Angiotensin II (Ang II) has been reported to induce migration in neuronal cell
      types. Using time-lapse microscopy, we show here that Ang II induces acceleration
      in NG108-15 cell migration. This effect was antagonized by PD123319, a selective
      AT2 receptor antagonist, but not by DUP753, a selective AT1 receptor antagonist,
      and was mimicked by the specific AT2 receptor agonist CGP42112. This Ang II
      induced acceleration was not sensitive to the inhibition of previously described
      signaling pathways of the AT2 receptor, guanylyl cyclase/cyclic GMP or p42/p44
      mapk cascades, but was abolished by pertussis toxin treatment and involved PP2A
      activation. Immunofluorescence studies indicate that Ang II or CGP42112 decreased
      the amount of filamentous actin at the leading edge of the cells. This decrease
      was accompanied by a concomitant increase in globular actin levels. Regulation of
      actin turnover in actin-based motile systems is known to be mainly under the
      control of the actin depolymerizing factor and cofilin. Basal migration speed
      decreased by 77.2% in cofilin-1 small interfering RNA-transfected NG108-15 cells,
      along with suppression of the effect of Ang II. In addition, the Ang II-induced
      increase in cell velocity was abrogated in serum-free medium as well as by
      genistein or okadaic acid treatment in a serum-containing medium. Such results
      indicate that the AT2 receptor increases the migration speed of NG108-15 cells
      and involves a tyrosine kinase activity, followed by phosphatase activation,
      which may be of the PP2A type. Therefore, the present study identifies actin
      depolymerization and cofilin as new targets of AT2 receptor action, in the
      context of cellular migration.

PMID- 18326003
TI  - In memory of Roger W. Jeanloz, a pioneer glycobiologist (1917-2007).

PMID- 18326004
TI  - The Roy L. Whistler International Award in Carbohydrate Chemistry 2008.

PMID- 18326005
TI  - Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency.
AB  - Congenital adrenal hyperplasia (CAH) describes a group of autosomal recessive
      disorders where there is impairment of cortisol biosynthesis. CAH due to 21
      hydroxylase deficiency accounts for 95% of cases and shows a wide range of
      clinical severity. Treatment of the classic or severe form of CAH is targeted at
      replacing cortisol and aldosterone and effectively controlling excess androgen
      symptoms by using the lowest possible glucocorticoid dose. Treatment of the mild
      or nonclassic form is targeted at controlling excess androgen symptoms and may or
      may not involve glucocorticoid therapy. Hydrocortisone is the treatment of choice
      for children, but there is no consensus on how patients should be treated as
      adults. Current glucocorticoid therapy is suboptimal because it is often
      difficult to reduce excess androgen without giving excess glucocorticoid, and
      patients may experience hypercortisolism, androgen excess, or a combination of
      these states. Treatment of CAH, especially in the adult patient, remains
      controversial given the lack of prospective randomized controlled trials
      comparing treatment regimens. Nevertheless, patients benefit from careful
      individualized therapy with avoidance of Cushingoid side effects and optimization
      of reproductive, sexual, and bone health.

PMID- 18326006
TI  - Infection and autoimmune thyroid disease.

PMID- 18326007
TI  - Contemporary surgical or percutaneous management of severe aortic stenosis in the
      elderly.
AB  - AIMS: To assess patient characteristics, therapeutic options, and their results
      in patients referred to a tertiary centre with on-site capabilities for surgical
      and percutaneous valvular interventions for the management of severe symptomatic
      aortic stenosis (AS). METHODS AND RESULTS: Sixty-six consecutive patients >70
      years (83 +/- 6 years) were referred for severe AS. Their mortality risk
      predicted by the logistic European System for Cardiac Operative Risk Evaluation
      and the Society of Thoracic Surgeons-Predicted Risk of Mortality scores were on
      average 20 +/- 14% and 17 +/- 7%, respectively. Thirty-nine patients (59%) were
      considered at high-risk for surgery or inoperable after multidisciplinary
      evaluation: 12 (31%) underwent a transfemoral aortic valve implantation and 27
      were considered unsuitable and treated medically (n = 16) or with valvuloplasty
      (n = 7), or were re-directed towards surgery (n = 4). The 27 other patients
      underwent valve replacement. In-hospital mortality was 9% (6 of 66). There were
      three hospital deaths in patients treated percutaneously, two in those treated
      medically, and one after surgery. At 6 months, 10% (6 of 60) of the survivors
      died: two after valvuloplasty and four after medical treatment. CONCLUSION: A
      large proportion of elderly patients referred for management of severe AS have a
      high-risk profile. The availability of percutaneous valvular interventions
      increases the number of those who are offered interventions.

PMID- 18326008
TI  - Relative survival: what can cardiovascular disease learn from cancer?
AB  - AIMS: To illustrate the application of relative survival to observational studies
      in coronary heart disease (CHD) and potential advantages compared with all-cause
      survival methods. Survival after myocardial infarction (MI) is generally assessed
      using all-cause or cause-specific methods. Neither method is able to assess the
      impact of the disease or condition of interest in comparison with expected
      survival in a similar population. Relative survival, the ratio of the observed
      and the expected survival rates, is applied routinely in cancer studies and may
      improve on current methods for assessment of survival in CHD. METHODS AND
      RESULTS: Using a cohort of subjects after a first recorded acute MI, we discuss
      the application of relative survival in CHD and illustrate a number of the key
      issues. We compare the findings from relative survival with those obtained using
      Cox proportional and non-proportional hazards models in standard all-cause
      survival. Estimated survival rates are higher using relative survival models
      compared with all-cause methods. CONCLUSION: Estimates obtained from all-cause
      mortality fail to disentangle mortality associated with the condition of interest
      from that due to all other causes. Relative survival gives an estimate of
      survival due to the disease of interest without the need for cause of death
      information.

PMID- 18326009
TI  - Basal carcinoma of the breast revisited: an old entity with new interpretations.
AB  - The introduction of global gene expression analysis in breast cancer research has
      focused attention onto a repeatedly described subgroup of invasive breast cancer,
      the basal-like carcinomas. This subgroup is characterised by the expression of
      high-molecular weight cytokeratins 5, 14 and 17; using immunohistochemical
      diagnosis, it represents approximately 7-20% of invasive breast cancers. Some of
      these tumours fulfil the criteria of grade 3 invasive ductal carcinoma, the so
      called triple negative carcinomas. However, other rare subgroups of metaplastic,
      medullary and myoepithelial carcinomas also belong to this entity. Even though
      the initial clinical prognostic relevance of basal-like breast cancers may have
      been overestimated, its distinctive biology generates many questions regarding
      the pathogenesis, chemosensitivity and optimal clinical management of this
      subgroup. Physiological progenitor cells within the normal female breast share
      essential immunohistochemical features with basal-like breast cancers. Although
      the exact relationship between subgroups of normal breast cells and their
      respective malignant counterparts is still under investigation, the major
      hallmarks of physiological progenitor cells are either maintained or reactivated
      by distinct genetic changes in basal breast cancer cells. This review will
      discuss the impact of these findings on our global understanding of breast cancer
      pathogenesis, especially from the perspective of its potential histogenesis.
      Clinical consequences and potential future research directions driven by the
      definition of basal breast cancers will also be discussed.

PMID- 18326010
TI  - A quality assurance exercise to evaluate the accuracy and reproducibility of
      chromogenic in situ hybridisation for HER2 analysis in breast cancer.
AB  - BACKGROUND: Chromogenic in situ hybridisation (CISH) is an alternative to
      immunohistochemistry or FISH for the assessment of HER2 oncogene status in breast
      cancer. Although CISH is being used increasingly in routine diagnostics, there
      are no established inter-laboratory quality assurance programmes for this test.
      METHODS: The reproducibility of HER2 CISH analysis was assessed when performed by
      seven different centres that use the test routinely in diagnostic service.
      RESULTS: The results from 28 cases showed overall concordance of 98.5% (192/195
      tests; kappa coefficient 0.91). One of the discrepancies was due to the invasive
      carcinoma having been cut out in the sections received by two of the centres, and
      the other two were in the non-amplified/equivocal/low-amplified category.
      CONCLUSION: This is believed to be the first report of a quality assurance study
      assessing laboratories that use HER2 CISH routinely in clinical diagnostics. The
      results show that CISH is a robust technique providing a suitable assay for the
      frontline testing of HER2 status in breast cancer.

PMID- 18326011
TI  - Technical pitfalls potentially affecting diagnoses in immunohistochemistry.
AB  - Result of the immunohistochemical reactions routinely used in diagnostic surgical
      pathology should be properly interpreted, since false results, related to
      technical and interpretative pitfalls may lead to incorrect diagnosis. The main
      sources of such pitfalls are reviewed, analytically described and related to
      different steps (fixation, tissue processing and embedding, decalcification,
      antigen retrieval) which may affect the accuracy of immunohistochemistry. In
      addition, the presence of endogenous enzyme activity, improper binding of avidin
      to endogenous biotin, incorrect use of antibodies, chromogen and detection
      systems, as well as incorrect interpretation may produce unreliable data. The
      high frequency and extension of such pitfalls make mandatory the use of internal
      and external controls and adoption of cross-validation programmes. The present
      study, supported by an extensive review of the related literature, is intended as
      a guideline leading to proper interpretation of immunohistochemical data, an
      essential component of the diagnostic process. Experience on the antigen
      retrieval procedures for different antigens is also presented.

PMID- 18326012
TI  - Guidelines for the macroscopic processing of radical prostatectomy and pelvic
      lymphadenectomy specimens.

PMID- 18326013
TI  - Clinical importance of the presence of giant cells in temporal arteritis.
AB  - BACKGROUND: The clinical significance of giant cells seen on temporal artery
      biopsy in temporal arteritis is unknown. AIM: To help define the prognostic value
      of the presence of giant cells in temporal arteritis. METHODS: The clinical
      course of all patients with biopsy proven temporal arteritis from 1994 to 2004
      was reviewed. The 92 patients were divided into those with giant cells (GC) (n =
      76) seen on biopsy and those with no giant cells (NGC) (n = 16). Clinical
      findings were compared between groups. An additional analysis combined results
      with a previous study at the same institution to compare occurrence of blindness.
      RESULTS: The GC group had a higher proportion of polymyalgia rheumatica (PMR)
      (36.8%) compared to the NGC group (12.5%) (p = 0.059). There was no significant
      difference in patient age, sex, sedimentation rate, or presenting symptoms. The
      length of time treated with corticosteroids and relapse rate was nearly identical
      for both groups. When combining data with the previous study, in the GC group
      21/109 (19%) developed blindness, while only 2/34 (6%) became blind in the NGC
      group (p = 0.11). CONCLUSION: The presence of giant cells is not a significant
      factor in determining treatment or clinical progression of temporal arteritis.
      However, results showed the GC group to have three times the occurrence of
      blindness and PMR compared to the NGC group. Although the differences were not
      significant, this analysis suggests an association with giant cells and more
      aggressive disease.

PMID- 18326014
TI  - Salmonella Michigan soft tissue infection in an immunocompromised child.
AB  - A rare case of soft tissue infection due to Salmonella Michigan in an
      immunocompromised child is reported. The same organism was isolated from a
      tortoise kept in the home. Immunocompromised patients are especially susceptible
      to reptile-associated salmonellosis and should be advised appropriately.

PMID- 18326015
TI  - Genetically determined susceptibility to mycobacterial infection.
AB  - Individuals with impaired cell mediated immunity exhibit increased susceptibility
      to infections caused by poorly pathogenic mycobacteria (non-tuberculous
      mycobacteria and BCG), as well as salmonella species. However, these infections
      may also occur in a disseminated, fatal form, sometimes with a familial
      distribution, in the absence of any recognised primary or secondary
      immunodeficiency. Genetic analysis of affected families has defined mutations in
      seven different genes participating in the interleukin 12 (IL12) dependent, high
      output interferon gamma (IFNgamma) pathway. The first category of defect is
      mutations in the IFNgammaR1 or R2 genes, resulting in defective expression or
      function of the IFNgamma receptor. The second category of mutations abrogates the
      cell surface expression IL12Rbeta1gene, resulting in the inability to respond to
      IL12. The third category of defect is the inability to produce IL12, due to
      deletion within the gene coding for the inducible chain of IL12 (IL12-p40).
      Patients with X-linked recessive mutations of the gene encoding the NFkappaB
      essential modulator may also develop mycobacterial infections, although they
      usually have a more complex phenotype and are susceptible to a broad spectrum of
      pathogens. Mutations of the gene encoding the signal transducing molecule STAT1,
      which impairs the ability to respond to IFNgamma, and mutations of the gene
      encoding TYK2 (which is associated with a failure to respond to IL12), are both
      rare genetic defects predisposing to mycobacterial infections. This review
      summarises the clinical spectrum seen in this group of patients and indicates a
      strategy for the identification of putative genetic defects in the type-1
      cytokine pathway.

PMID- 18326016
TI  - Reference change values: how useful are they?

PMID- 18326017
TI  - Prognostic and predictive factors in colorectal cancer.
AB  - Prognostication of newly diagnosed colorectal cancer (CRC) predominantly relies
      on stage as defined by the UICC-TNM and American Joint Committee on Cancer
      classifications. Tumour extent, lymph node status, tumour grade and the
      assessment of lymphatic and venous invasion are still the most important
      morphological prognostic factors. Evidence suggests that tumour budding and
      tumour border configuration are important, additional histological parameters but
      are not regarded as essential in prognosis. Although several molecular features,
      such as LOH18q and TP53 mutation analysis, have shown promising results in terms
      of their prognostic value, the American Society of Clinical Oncology Tumor
      Markers Expert Panel does not currently recommend their use in routine practice.
      cDNA-microarray, PCR and fluorescence in situ hybridisation are now frequently
      used to identity potential prognostic indicators in CRC, but the applicability of
      these methods in routine use is likely to have limited impact. Reliable
      prognostic markers identified by immunohistochemical protein profiling have yet
      to be established. Randomisation of data sets, assessment of interobserver
      variability for protein markers and scoring systems, as well as the use of
      receiver operating characteristic curve analysis in combination with multimarker
      phenotype analysis of several different markers may be an effective tactical
      approach to increase the value of immunohistochemical findings. This article
      reviews the well established and additional prognostic factors in CRC and
      explores the contribution of molecular studies to the prognostication of patients
      with this disease. Additionally, an approach to improve the prognostic value of
      immunohistochemical protein markers is proposed.

PMID- 18326018
TI  - Automated immunostaining of cell smears: an alternative to flow cytometry.
AB  - AIMS: To assess the applicability of an automated tissue immunostainer machine
      for the phenotypic analysis of peripheral blood and bone marrow aspirate smears.
      METHODS: Air-dried smears of peripheral blood and bone marrow from normal
      individuals and 14 patients with haematological malignancies were stained,
      following fixation, with a range of antibodies to haemopoietic antigens using
      both immunoperoxidase and immuno-alkaline phosphatase methods on the Bond-maX
      (Leica Microsystems) automated immunostaining machine. RESULTS: Automated
      protocols used for staining formalin-fixed paraffin-embedded tissue could be
      applied to cell smears, giving high quality staining with excellent cytological
      detail and antigenic preservation for an extensive antibody panel. Optimal
      quality (morphological preservation and antigen detection without background
      staining) was obtained with an alkaline phosphatase method and Fast Red
      chromogenic substrate. Both cell surface and intracellular (cytoplasmic and
      nuclear) antigens could be detected and gave the expected reactivity.
      CONCLUSIONS: Automated immunostaining is possible for haematological smears. It
      generates consistent high quality staining, with the exception of surface
      immunoglobulin, and is applicable to haematological and, potentially, cytological
      smears. It provides a practical alternative to flow cytometry and will have
      particular application when smears are available and there is no suitable sample
      for flow cytometry.

PMID- 18326019
TI  - Value of CT-guided biopsy in the diagnosis of septic discitis.
AB  - AIM: To determine the role of CT-guided biopsy in the management of cases of
      infective discitis. METHODS: Data were examined from a retrospective case series
      of CT-guided biopsies for the 5-year period ending June 2006. RESULTS: 98 CT
      guided biopsies were performed in the study period on 103 patients. Malignancy
      was diagnosed in 49 episodes. Discitis and paravertebral abscess accounted for 27
      cases. Culture was positive in nine of 25 (36%) samples received by the
      microbiology laboratory. Staphylococcus aureus (four cases) and Mycobacterium
      tuberculosis (three cases) were the most frequent organisms isolated, followed by
      group G streptococci and coagulase-negative staphylococci (one case each). Blood
      cultures were diagnostic in a further nine patients. The main reason for a
      negative culture was prior antimicrobial therapy. The biopsy changed management
      in 9/25 (36%) of cases. There were no reported adverse events. CONCLUSION: Septic
      discitis is a serious condition with a wide variety of infective causes. CT
      guided biopsy is a useful tool when the diagnosis of infectious spinal infection
      is considered in terms of commencing and targeting therapy, and it is a safe and
      well-tolerated procedure.

PMID- 18326020
TI  - High expression of Polycomb group protein EZH2 predicts poor survival in salivary
      gland adenoid cystic carcinoma.
AB  - BACKGROUND: The prognosis of adenoid cystic carcinoma (ACC), a malignant salivary
      gland tumour, depends on clinicopathological parameters. To decipher the
      biological behaviour of ACC, and to identify patients at risk of developing
      metastases, additional markers are needed. METHODS: Expression of the cell cycle
      proteins p53, cyclin D1, p16(INK4a), E2F1 and Ki-67, together with the Polycomb
      group (PcG) proteins BMI-1, MEL-18, EZH2 and EED was investigated
      immunohistochemically 21 formalin-fixed, paraffin-embedded primary ACCs in
      relation to tumour characteristics. RESULTS: ACC revealed significantly increased
      expression of the cell cycle proteins compared to normal salivary tissue (n =
      17). Members of the two PcG complexes displayed mutually exclusive expression in
      normal salivary gland tissue, with BMI-1 and MEL-18 being abundantly present. In
      ACC, this expression pattern was disturbed, with EZH2 and EED showing
      significantly increased expression levels. In univariate analysis, presence of
      recurrence, poor differentiation and high EZH2 levels (>25% immunopositivity)
      significantly correlated with unfavourable outcome. ACCs with high proliferative
      rate (>25% Ki-67 immunopositivity) significantly correlated with high levels of
      EZH2 and p16. Only the development of recurrence was an independent prognostic
      factor of survival in multivariate analysis. CONCLUSIONS: Expression of PcG
      complexes and of essential cell cycle proteins is highly deregulated in ACC.
      Also, EZH2 expression has prognostic relevance in this malignancy.

PMID- 18326021
TI  - Vacuum assisted stereotactic guided mammotome biopsies in the management of
      screen detected microcalcifications: experience of a large breast screening
      centre.
AB  - AIM: To evaluate the usefulness of vacuum assisted stereotactic guided mammotome
      biopsy in the diagnostic management of screen detected calcifications and to
      rationalise its use versus diagnostic excision. METHODS: The first 100 mammotome
      biopsies preceded by a conventional needle core biopsy (NCB) were identified from
      the database of Leeds/Wakefield Breast Screening Service. The histological
      diagnosis on NCB and mammotome were reviewed and compared with the surgical
      histological diagnosis if excision had been performed. RESULTS: Using mammotome,
      diagnoses were changed in 74 of the 100 cases. In 66 cases a definitive diagnosis
      (B2 or B5) was obtained. The incidence of inadequate/unsatisfactory (B1) biopsies
      was reduced from 36% to 9%. In 34 cases mammotome was not helpful in arriving at
      a definite diagnosis (B1/B3/B4). All cases diagnosed as malignant with mammotome
      were proven to have in situ or invasive malignancy on excision except for one
      case of ductal carcinoma in situ fully excised by mammotome. There was one false
      negative case of in-situ carcinoma with a prior benign (B2) mammotome diagnosis.
      Almost half the NCB uncertain (B3) cases required excision as the mammotome
      biopsies were also uncertain (B3). The majority were flat epithelial atypia and
      atypical intraductal proliferation. CONCLUSIONS: Mammotome biopsy is particularly
      useful for further assessment of an inadequate (B1) or suspicious (B4) NCB
      diagnosis. Diagnostic surgical excision remains the method of choice for managing
      atypical/uncertain lesions (B3).

PMID- 18326022
TI  - The histological diagnosis of leprosy type 1 reactions: identification of key
      variables and an analysis of the process of histological diagnosis.
AB  - BACKGROUND: Type 1 leprosy reactions (T1R) are a major inflammatory complication
      of leprosy affecting 30% of patients with borderline leprosy, but there has been
      no diagnostic evaluation of the histological diagnosis of this entity. METHODS:
      In a prospective study based in India, skin biopsies were taken from 99 patients
      with clinically diagnosed T1R and 52 non-reactional controls. These were assessed
      histologically by four histopathologists whose assessments were then compared.
      RESULTS: Reactions were under-diagnosed, with 32-62% of clinically diagnosed
      reactions being given a histological diagnosis. The pathologists showed good
      specificities (range 72% to 93%) but much poorer sensitivities (range 42% to
      78%). The most commonly reported histological features of TIR were cell maturity,
      oedema and giant cells. Five key variables were identified that the pathologists
      used in diagnosing a reaction: intra-granuloma oedema, giant cell size, giant
      cell numbers, dermal oedema and HLA-DR expression. A predictive model for the
      diagnosis of T1R was developed using stepwise logistic regression analysis, with
      clinical diagnosis of reaction as an outcome, and then identification of the key
      variables that each pathologist used in making the diagnosis of T1R. 34-53% of
      the variation between pathologists could be accounted for. The four pathologists
      used a similar diagnostic model and for all of them their estimations of
      epithelioid cell granuloma oedema, dermal oedema, plasma cells and granuloma
      fraction were significant variables in the diagnosis of T1R. Each pathologist
      then added in variables that were specific to themselves. CONCLUSIONS: This study
      has identified T1R as being under-diagnosed in comparison with clinical
      assessments. Key variables for diagnosing T1R were established. This comparative
      masked study highlights the need for such studies in other inflammatory
      conditions.

PMID- 18326023
TI  - Aortic stent grafts.
AB  - Abdominal aortic aneurysms (AAAs) occur when weakened areas of the abdominal
      aortic wall result in a ballooning of the blood vessel. Attributed risk factors
      include smoking, atherosclerosis and hypertension. Traditionally, AAAs were
      treated with open surgery, involving a large abdominal incision and the placement
      of a synthetic graft. The introduction of endovascular aneurysm repair (EVAR)
      however, proved to have many advantages over open repair, chief among which is a
      lower perioperative morbidity and mortality rate. EVAR is likely to continue to
      evolve and the complications associated with this procedure will likely continue
      to decrease. In the meantime, the benefit of the continued, detailed analyses of
      explanted devices is twofold: (1) for future development of new devices; and (2)
      cognisance of complications that arise with any new device. This review is a
      guide to the many FDA approved stents which are commercially available, and those
      likely to become available following clinical trials.

PMID- 18326024
TI  - Histone deacetylase 3 localizes to the mitotic spindle and is required for
      kinetochore-microtubule attachment.
AB  - Protein acetylation and deacetylation play key roles in multiple physiological
      functions. Histone deacetylase 3 (HDAC3) is a highly conserved, ubiquitously
      expressed protein that forms multiprotein corepressor complexes to repress gene
      transcription. Recent studies show that HDAC3 may play a role in cell
      proliferation. Altered HDAC3 level increases G(2)/M cells, but the mechanism
      remains unknown. Here we show for the first time, to our knowledge, that the
      HDAC3 complex, including nuclear receptor corepressor (N-CoR), transducin-beta
      like protein 1 (TBL1), and TBL1-related protein 1 (TBLR1), is localized on the
      mitotic spindle. Knockdown of HDAC3 or N-CoR resulted in a collapsed mitotic
      spindle that was surrounded by chromosomes arranged in a dome-like configuration.
      Treatment of mitotic cells with Trichostatin A, an HDAC inhibitor, resulted in
      similar spindle defects independent of transcriptional regulation. In addition,
      wild-type HDAC3 but not a deacetylase-dead mutant HDAC3 rescued the phenotypes of
      HDAC3-depleted cells, suggesting that the enzymatic activity of HDAC3 is
      important for proper spindle function. Whereas the kinetochores and the spindle
      assembly checkpoint appeared intact in HDAC3-deficient cells, kinetochore
      microtubule attachments were impaired because spindle microtubules were unstable
      in response to cold treatment. These data suggest that the HDAC3 complex is
      involved in the formation of functional mitotic spindles and proper kinetochore
      microtubule attachment. The level or distribution of acetylated alpha-tubulin was
      not altered in HDAC3-deficient cells. Taken together, our studies raise the
      interesting possibility that acetylation-deacetylation of mitotic spindle
      components may be essential for mitotic spindle function.

PMID- 18326025
TI  - Evidence for olfactory search in wandering albatross, Diomedea exulans.
AB  - Wandering albatrosses (Diomedea exulans) forage over thousands of square
      kilometers of open ocean for patchily distributed live prey and carrion. These
      birds have large olfactory bulbs and respond to fishy-scented odors in at-sea
      trials, suggesting that olfaction plays a role in natural foraging behavior. With
      the advent of new, fine-scale tracking technologies, we are beginning to explore
      how birds track prey in the pelagic environment, and we relate these observations
      to models of odor transport in natural situations. These models suggest that
      odors emanating from prey will tend to disperse laterally and downwind of the
      odor source and acquire an irregular and patchy concentration distribution due to
      turbulent transport. For a seabird foraging over the ocean, this scenario
      suggests that olfactory search would be facilitated by crosswind flight to
      optimize the probability of encountering a plume emanating from a prey item,
      followed by upwind, zigzag flight to localize the prey. By contrast, birds
      approaching prey by sight would be expected to fly directly to a prey item,
      irrespective of wind direction. Using high-precision global positioning system
      (GPS) loggers in conjunction with stomach temperature recorders to simultaneously
      monitor feeding events, we confirm these predictions in freely ranging wandering
      albatrosses. We found that initial olfactory detection was implicated in nearly
      half (46.8%) of all flown approaches preceding prey-capture events, accounting
      for 45.5% of total prey mass captured by in-flight foraging. These results offer
      insights into the sensory basis for area-restricted search at the large spatial
      scales of the open ocean.

PMID- 18326026
TI  - Bet-hedging and epigenetic inheritance in bacterial cell development.
AB  - Upon nutritional limitation, the bacterium Bacillus subtilis has the capability
      to enter the irreversible process of sporulation. This developmental process is
      bistable, and only a subpopulation of cells actually differentiates into
      endospores. Why a cell decides to sporulate or not to do so is poorly understood.
      Here, through the use of time-lapse microscopy, we follow the growth, division,
      and differentiation of individual cells to identify elements of cell history and
      ancestry that could affect this decision process. These analyses show that during
      microcolony development, B. subtilis uses a bet-hedging strategy whereby some
      cells sporulate while others use alternative metabolites to continue growth,
      providing the latter subpopulation with a reproductive advantage. We demonstrate
      that B. subtilis is subject to aging. Nevertheless, the age of the cell plays no
      role in the decision of its fate. However, the physiological state of the cell's
      ancestor (more than two generations removed) does affect the outcome of cellular
      differentiation. We show that this epigenetic inheritance is based on positive
      feedback within the sporulation phosphorelay. The extended intergenerational
      "memory" caused by this autostimulatory network may be important for the
      development of multicellular structures such as fruiting bodies and biofilms.

PMID- 18326028
TI  - The epidemiology of AIDS in Haiti refutes the claims of Gilbert et al.

PMID- 18326029
TI  - Hibernation can also cause high delta15N values in cave bears: a response to
      Richards et al.

PMID- 18326030
TI  - A mitotic recombination system for mouse chromosome 17.
AB  - Mitotic recombination between homologous chromosomes is a genetic technique for
      mosaic analysis in model organisms. The general application of this technique in
      the mouse depends on establishment of effective recombination systems for
      individual chromosomes and reliable and sensitive methods for detection of
      recombination events. Here, we established a Cre/LoxP-mediated recombination
      system in mice for mosaic analysis of full-length chromosome 17. Cre-mediated
      germ-line recombination between the homologous chromosomes was observed with
      approximately 9% frequency in a progeny test. Mitotic recombination in somatic
      tissues was evaluated and scored in B and T lymphocytes with the aid of surface
      markers and fluorescent-activated cell sorting. We show that a lineage-specific
      Cre can induce mitotic recombination with a highly reproducible frequency of 0.5
      1.0% in lymphoid progenitors. The recombination system established here allows
      for a simple and accurate detection and isolation of recombination events in live
      cells, making this system particularly attractive for mosaic analysis or
      mutagenesis studies in the immune system.

PMID- 18326031
TI  - The AU-rich element mRNA decay-promoting activity of BRF1 is regulated by mitogen
      activated protein kinase-activated protein kinase 2.
AB  - Regulated mRNA decay is a highly important process for the tight control of gene
      expression. Inherently unstable mRNAs contain AU-rich elements (AREs) in the 3'
      untranslated regions that direct rapid mRNA decay by interaction with decay
      promoting ARE-binding proteins (ARE-BPs). The decay of ARE-containing mRNAs is
      regulated by signaling pathways that are believed to directly target ARE-BPs.
      Here, we show that BRF1 involved in ARE-mediated mRNA decay (AMD) is
      phosphorylated by MAPK-activated protein kinase 2 (MK2). In vitro kinase assays
      using different BRF1 fragments suggest that MK2 phosphorylates BRF1 at four
      distinct sites, S54, S92, S203, and an unidentified site at the C terminus.
      Coexpression of an active form of MK2 inhibits ARE mRNA decay activity of BRF1.
      MK2-mediated inhibition of BRF1 requires phosphorylation at S54, S92, and S203.
      Phosphorylation of BRF1 by MK2 does not appear to alter its ability to interact
      with AREs or to associate with mRNA decay enzymes. Thus, MK2 inhibits BRF1
      dependent AMD through direct phosphorylation. Although the mechanism underlying
      this inhibition is still unclear, it appears to target BRF1-dependent AMD at a
      level downstream from RNA binding and the recruitment of mRNA decay enzymes.

PMID- 18326032
TI  - Individual skill progression on a virtual reality simulator for shoulder
      arthroscopy: a 3-year follow-up study.
AB  - BACKGROUND: Previous studies have demonstrated a correlation between surgical
      experience and performance on a virtual reality arthroscopy simulator but only
      provided single time point evaluations. Additional longitudinal studies are
      necessary to confirm the validity of virtual reality simulation before these
      teaching aids can be more fully recommended for surgical education. HYPOTHESIS:
      Subjects will show improved performance on simulator retesting several years
      after an initial baseline evaluation, commensurate with their advanced surgical
      experience. STUDY DESIGN: Controlled laboratory study. METHODS: After gaining
      further arthroscopic experience, 10 orthopaedic residents underwent retesting 3
      years after initial evaluation on a Procedicus virtual reality arthroscopy
      simulator. Using a paired t test, simulator parameters were compared in each
      subject before and after additional arthroscopic experience. Subjects were
      evaluated for time to completion, number of probe collisions with the tissues,
      average probe velocity, and distance traveled with the tip of the simulated probe
      compared to an optimal computer-determined distance. In addition, to evaluate
      consistency of simulator performance, results were compared to historical
      controls of equal experience. RESULTS: Subjects improved significantly (P < .02
      for all) in the 4 simulator parameters: completion time (-51%), probe collisions
      (-29%), average velocity (+122%), and distance traveled (-32%). With the
      exception of probe velocity, there were no significant differences between the
      performance of this group and that of a historical group with equal experience,
      indicating that groups with similar arthroscopic experience consistently
      demonstrate equivalent scores on the simulator. CONCLUSION: Subjects
      significantly improved their performance on simulator retesting 3 years after
      initial evaluation. Additionally, across independent groups with equivalent
      surgical experience, similar performance can be expected on simulator parameters;
      thus it may eventually be possible to establish simulator benchmarks to indicate
      likely arthroscopic skill. CLINICAL RELEVANCE: These results further validate the
      use of surgical simulation as an important tool for the evaluation of surgical
      skills.

PMID- 18326033
TI  - A biomechanical comparison of 2 technical variations of double-row rotator cuff
      fixation: the importance of medial row knots.
AB  - BACKGROUND: Previous studies have shown comparable biomechanical properties of
      double-row fixation versus double-row fixation with a knotless lateral row.
      SutureBridge is a construct that secures the cuff with medial row mattress suture
      anchors and knotless lateral row fixation of the medial suture ends. Recent
      completely knotless constructs may lead to lesser clinical outcomes if the
      construct properties are compromised from lack of suture knots. HYPOTHESIS: A
      completely knotless construct without medial row knots will compromise the
      biomechanical properties in both cyclic and failure-testing parameters. STUDY
      DESIGN: Controlled laboratory study. METHODS: Six matched pairs of cadaveric
      shoulders were randomized to 2 groups of double row fixation with SutureBridge:
      group 1 with medial row knots, and group 2 without medial row knots. The
      specimens were placed in a materials test system at 30 degrees of abduction.
      Cyclic testing to 180 N at 1 mm/sec for 30 cycles was performed, followed by
      tensile testing to failure at 1 mm/sec. RESULTS: Data included cyclic and failure
      data from the materials test system and gap data using a video digitizing system.
      All data from paired specimens were compared using paired Student t tests. Group
      1 had a statistically significant difference (P < .05) for gap formation for the
      1st (3.47 vs 5.05 mm) and 30th cycle (4.22 vs 8.10 mm) and at yield load (5.2 vs
      9.1 mm). In addition, there was a greater energy absorbed (2805 vs 1648 N-mm),
      yield load (233 vs 183.1 N), and ultimate load (352.9 vs 253.9 N) for group 1.
      The mode of failure for the majority (4/6) of group 2 was lateral row failure,
      whereas all group 1 specimens failed at the clamp. CONCLUSION: Although lateral
      row knotless fixation has been shown not to sacrifice structural integrity of
      this construct, the addition of a knotless medial row compromises the construct
      leading to greater gapping and failure at lower loads. CLINICAL RELEVANCE: This
      may raise concerns regarding recently marketed completely knotless double row
      constructs.

PMID- 18326034
TI  - The influence of soccer-specific fatigue on peak isokinetic torque production of
      the knee flexors and extensors.
AB  - BACKGROUND: Epidemiological findings of higher muscular thigh strain injury
      incidence during the latter stages of soccer match play have been attributed to
      fatigue. HYPOTHESIS: Soccer-specific fatigue will significantly reduce peak
      isokinetic torque of the knee flexors and extensors. STUDY DESIGN: Descriptive
      laboratory study. METHODS: Ten male professional soccer players (mean age, 24.7
      +/- 4.4 years; body mass, 77.1 +/- 8.3 kg; maximum oxygen consumption [VO(2)
      max], 63.0 +/- 4.8 mL/kg/min) completed an intermittent treadmill protocol
      replicating the activity profile of match play. Before exercise and at 15-minute
      intervals, each player completed 1 of 2 randomized isokinetic dynamometer
      protocols. The first protocol quantified peak concentric knee extensor and flexor
      torque, while the second quantified peak concentric and eccentric knee flexor
      torque at isokinetic speeds of 180, 300, and 60 deg/s (3.14, 5.25, and 1.05
      rad/s) with 5 repetitions at each speed. RESULTS: Concentric knee extensor and
      flexor peak torque were maintained throughout the duration of the exercise
      protocol, irrespective of movement speed. However, peak eccentric knee flexor
      torques at the end of the game (T(300eccH105) = 127 +/- 25 N.m) and at the end of
      the passive half-time interval (T(300eccH60) = 133 +/- 32 N.m) were significantly
      reduced relative to the first 15 minutes (T(300eccH00) = 167 +/- 35 N.m, P < .01;
      T(300eccH15) = 161 +/- 35 N.m, P = .02). CONCLUSION: Eccentric knee flexor
      strength decreases as a function of time and after the half-time interval.
      CLINICAL RELEVANCE: This suggests a greater risk of injuries at these specific
      times, especially for explosive movements, in accord with epidemiological
      observations.

PMID- 18326035
TI  - Microgeodic disease affecting the toes in athletes: a report of 2 cases.

PMID- 18326036
TI  - Activation domain-dependent monoubiquitylation of Gal4 protein is essential for
      promoter binding in vivo.
AB  - The Saccharomyces cerevisiae Gal4 protein is a paradigmatic transcriptional
      activator containing a C-terminal acidic activation domain (AD) of 34 amino
      acids. A mutation that results in the truncation of about two-thirds of the
      Gal4AD (gal4D) results in a crippled protein with only 3% the activity of the
      wild-type activator. We show here that although the Gal4D protein is not
      intrinsically deficient in DNA binding, it is nonetheless unable to stably occupy
      GAL promoters in vivo. This is because of the activity of the proteasomal
      ATPases, including Sug1/Rpt6, which bind to Gal4D via the remainder of the AD and
      strip it off of DNA. A mutation that suppressed the Gal4D "no growth on
      galactose" phenotype repressed the stripping activity of the ATPase complex but
      not other activities. We further demonstrate that Gal4D is hypersensitive to this
      stripping activity because of its failure to be monoubiquitylated efficiently in
      vivo and in vitro. Evidence is presented that the piece of the AD that is deleted
      in Gal4D protein is likely a recognition element for the E3 ubiquitin-protein
      ligase that modifies Gal4. These data argue that acidic ADs comprise at least two
      small peptide subdomains, one of which is responsible for activator
      monoubiquitylation and another that interacts with the proteasomal ATPases,
      coactivators and other transcription factors. This study validates the
      physiological importance of Gal4 monoubiquitylation and clarifies its major role
      as that of protecting the activator from being destabilized by the proteasomal
      ATPases.

PMID- 18326037
TI  - An intramolecular route for coupling ATPase activity in AAA+ proteins for
      transcription activation.
AB  - AAA+ proteins (ATPases associated with various cellular activities) contribute to
      many cellular processes and typically function as higher order oligomers
      permitting the coordination of nucleotide hydrolysis for functional output, which
      leads to substrate remodeling. The precise mechanisms that enable the relay of
      nucleotide hydrolysis to their specific functional outputs are largely unknown.
      Here we use PspF, a specialized AAA+ protein required for enhancer-dependent
      transcription activation in Escherichia coli, as a model system to address this
      question. We demonstrate that a conserved asparagine is involved in internal
      organization of the oligomeric ring, regulation of ATPase activity by "trans"
      factors, and optimizing substrate remodeling. We provide evidence that the
      spatial relationship between the asparagine residue and the Walker B motif is one
      key element in the conformational signaling pathway that leads to substrate
      remodeling. Such functional organization most likely applies to other AAA+
      proteins, including Ltag (simian virus 40), Rep40 (Adeno-associated virus-2), and
      p97 (Mus musculus) in which the asparagine to Walker B motif relationship is
      conserved.

PMID- 18326038
TI  - The inhalation anesthetic desflurane induces caspase activation and increases
      amyloid beta-protein levels under hypoxic conditions.
AB  - Perioperative factors including hypoxia, hypocapnia, and certain anesthetics have
      been suggested to contribute to Alzheimer disease (AD) neuropathogenesis.
      Desflurane is one of the most commonly used inhalation anesthetics. However, the
      effects of desflurane on AD neuropathogenesis have not been previously
      determined. Here, we set out to assess the effects of desflurane and hypoxia on
      caspase activation, amyloid precursor protein (APP) processing, and amyloid beta
      protein (Abeta) generation in H4 human neuroglioma cells (H4 naive cells) as well
      as those overexpressing APP (H4-APP cells). Neither 12% desflurane nor hypoxia
      (18% O(2)) alone affected caspase-3 activation, APP processing, and Abeta
      generation. However, treatment with a combination of 12% desflurane and hypoxia
      (18% O(2)) (desflurane/hypoxia) for 6 h induced caspase-3 activation, altered APP
      processing, and increased Abeta generation in H4-APP cells. Desflurane/hypoxia
      also increased levels of beta-site APP-cleaving enzyme in H4-APP cells. In
      addition, desflurane/hypoxia-induced Abeta generation could be reduced by the
      broad caspase inhibitor benzyloxycarbonyl-VAD. Finally, the Abeta aggregation
      inhibitor clioquinol and gamma-secretase inhibitor L-685,458 attenuated caspase-3
      activation induced by desflurane/hypoxia. In summary, desflurane can induce Abeta
      production and caspase activation, but only in the presence of hypoxia. Pending
      in vivo confirmation, these data may have profound implications for anesthesia
      care in elderly patients, and especially those with AD.

PMID- 18326039
TI  - Kinetic mechanism of fully activated S6K1 protein kinase.
AB  - S6K1 is a member of the AGC subfamily of serine-threonine protein kinases,
      whereby catalytic activation requires dual phosphorylation of critical residues
      in the conserved T-loop (Thr-229) and hydrophobic motif (Thr-389). Previously, we
      described production of the fully activated catalytic kinase domain construct,
      His(6)-S6K1alphaII(DeltaAID)-T389E. Now, we report its kinetic mechanism for
      catalyzing phosphorylation of a model peptide substrate (Tide, RRRLSSLRA). First,
      two-substrate steady-state kinetics and product inhibition patterns indicated a
      Steady-State Ordered Bi Bi mechanism, whereby initial high affinity binding of
      ATP (K(d)(ATP)=5-6 microM) was followed by low affinity binding of Tide
      (K(d)(Tide)=180 microM), and values of K(m)(ATP)=5-6 microM and K(m)(Tide)=4-5
      microM were expressed in the active ternary complex. Global curve-fitting
      analysis of ATP, Tide, and ADP titrations of pre-steady-state burst kinetics
      yielded microscopic rate constants for substrate binding, rapid chemical
      phosphorylation, and rate-limiting product release. Catalytic trapping
      experiments confirmed rate-limiting steps involving release of ADP. Pre-steady
      state kinetic and catalytic trapping experiments showed osmotic pressure to
      increase the rate of ADP release; and direct binding experiments showed osmotic
      pressure to correspondingly weaken the affinity of the enzyme for both ADP and
      ATP, indicating a less hydrated conformational form of the free enzyme.

PMID- 18326040
TI  - Critical contribution of aromatic rings to specific recognition of polyether
      rings. The case of ciguatoxin CTX3C-ABC and its specific antibody 1C49.
AB  - To address how proteins recognize polyether toxin compounds, we focused on the
      interaction between the ABC ring compound of ciguatoxin 3C and its specific
      antibody, 1C49. Surface plasmon resonance analyses indicated that Escherichia
      coli-expressed variable domain fragments (Fv) of 1C49 had the high affinity
      constants and slow dissociation constants typical of antigen-antibody
      interactions. Linear van't Hoff analyses suggested that the interaction is
      enthalpy-driven. We resolved the crystal structure of 1C49 Fv bound to ABC ring
      compound of ciguatoxin 3C at a resolution of 1.7A. The binding pocket of the
      antibody had many aromatic rings and bound the antigen by shape complementarity
      typical of hapten-antibody interactions. Three hydrogen bonds and many van der
      Waals interactions were present. We mutated several residues of the antibody to
      Ala, and we used surface plasmon resonance to analyze the interactions between
      the mutated antibodies and the antigen. This analysis identified Tyr-91 and Trp
      96 in the light chain as hot spots for the interaction, and other residues made
      incremental contributions by conferring enthalpic advantages and reducing the
      dissociation rate constant. Systematic mutation of Tyr-91 indicated that CH-pi
      and pi-pi interactions between the aromatic ring at this site and the antigen
      made substantial contributions to the association, and van der Waals interactions
      inhibited dissociation, suggesting that aromaticity and bulkiness are critical
      for the specific recognition of polyether compounds by proteins.

PMID- 18326041
TI  - The modulation of transthyretin tetramer stability by cysteine 10 adducts and the
      drug diflunisal. Direct analysis by fluorescence-detected analytical
      ultracentrifugation.
AB  - Transthyretin (TTR) is normally a stable plasma protein. However, in cases of
      familial TTR-related amyloidosis and senile systemic amyloidosis (SSA), TTR is
      deposited as amyloid fibrils, leading to organ dysfunction and possibly death.
      The mechanism by which TTR undergoes the transition from stable, soluble
      precursor to insoluble amyloid fibril and the factors that promote this process
      are largely undetermined. Most models involve the dissociation of the native TTR
      tetramer as the initial step. It is largely accepted that the TTR gene mutations
      associated with TTR-related amyloidosis lead to the expression of variant
      proteins that are intrinsically unstable and prone to aggregation. It has been
      suggested that amyloidogenicity may be conferred to wild-type TTR (the form
      deposited in SSA) by chemical modification of the lone cysteine residue (Cys(10))
      through mixed disulfide bonds. S-Sulfonation and S-cysteinylation are prevalent
      TTR modifications physiologically, and studies have suggested their ability to
      modulate the structure of TTR under denaturing conditions. In the present study,
      we have used fluorescence-detected sedimentation velocity to determine the effect
      of S-sulfonate and S-cysteine on the quaternary structural stability of
      fluorophore-conjugated recombinant TTR under nondenaturing conditions. We
      determined that S-sulfonation stabilized TTR tetramer stability by a factor of 7,
      whereas S-cysteinylation enhanced dissociation by 2-fold with respect to the
      unmodified form. In addition, we report the direct observation of tetramer
      stabilization by the potential therapeutic compound diflunisal. Finally, as proof
      of concept, we report the sedimentation of TTR in serum and the qualitative
      assessment of the resulting data.

PMID- 18326042
TI  - Substitution of pseudokinase domain residue Val-617 by large non-polar amino
      acids causes activation of JAK2.
AB  - Explaining the uniqueness of the acquired somatic JAK2 V617F mutation, which is
      present in more than 95% of polycythemia vera patients, has been a challenge. The
      V617F mutation in the pseudokinase domain of JAK2 renders the unmutated kinase
      domain constitutively active. We have performed random mutagenesis at position
      617 of JAK2 and tested each of the 20 possible amino acids for ability to induce
      constitutive signaling in Ba/F3 cells expressing the erythropoietin receptor.
      Four JAK2 mutants, V617W, V617M, V617I, and V617L, were able to induce cytokine
      independence and constitutive downstream signaling. Only V617W induced a level of
      constitutive activation comparable with V617F. Also, only V617W stabilized
      tyrosine-phosphorylated suppressor of cytokine signaling 3 (SOCS3), a mechanism
      by which JAK2 V617F overcomes inhibition by SOCS3. The V617W mutant induced a
      myeloproliferative disease in mice, mainly characterized by erythrocytosis and
      megakaryocytic proliferation. Although JAK2 V617W would predictably be pathogenic
      in humans, the substitution of the Val codon, GTC, by TTG, the codon for Trp,
      would require three base pair changes, and thus it is unlikely to occur. We
      discuss how the predicted conformations of the activated JAK2 mutants can lead to
      better screening assays for novel small molecule inhibitors.

PMID- 18326043
TI  - A novel GDP-dependent pyruvate kinase isozyme from Toxoplasma gondii localizes to
      both the apicoplast and the mitochondrion.
AB  - We previously reported a cytosolic pyruvate kinase (EC 2.7.1.40) from Toxoplasma
      gondii (TgPyKI) that differs from most eukaryotic pyruvate kinases in being
      regulated by glucose 6-phosphate rather than fructose 1,6-diphosphate. Another
      putative pyruvate kinase (TgPyKII) was identified from parasite genome, which
      exhibits 32% amino acid sequence identity to TgPyKI and retains pyruvate kinase
      signature motifs and amino acids essential for substrate binding and catalysis.
      Whereas TgPyKI is most closely related to plant/algal enzymes, phylogenetic
      analysis suggests a proteobacterial origin for TgPyKII. Enzymatic
      characterization of recombinant TgPyKII shows a high pH optimum at 8.5, and a
      preference for GDP as a phosphate recipient. Catalytic activity is independent of
      K+, and no allosteric or regulatory effects were observed in the presence of
      fructose 1,6-diphosphate, fructose 2,6-diphosphate, glucose 6-phosphate, ribose 5
      phosphate, AMP, or ATP. Unlike TgPyKI, native TgPyKII activity was exclusively
      associated with the membranous fraction of a T. gondii tachyzoite lysate. TgPyKII
      possesses a long N-terminal extension containing five putative start codons
      before the conserved region and localizes to both apicoplast and mitochondrion by
      immunofluorescence assay using native antibody and fluorescent protein fusion to
      the N-terminal extension. Further deletional and site-directed mutagenesis
      suggests that a translation product from 1st Met is responsible for the
      localization to the apicoplast, whereas one from 3rd Met is for the
      mitochondrion. This is the first study of a potential mitochondrial pyruvate
      kinase in any system.

PMID- 18326044
TI  - APOBEC3G is degraded by the proteasomal pathway in a Vif-dependent manner without
      being polyubiquitylated.
AB  - Although the covalent attachment of a polyubiquitin is the prevailing paradigm
      for entry into proteasomes, accumulating evidence suggests that poorly defined
      ubiquitin-free pathways also degrade proteins. The cytidine deaminase APOBEC3G
      (A3G) potently inhibits human immunodeficiency virus type 1 replication by
      disrupting viral reverse transcription. However, human immunodeficiency virus
      type 1 produces a viral infectivity factor (Vif) to destroy this antiretroviral
      protein. It was shown that Vif binds to both A3G and a Cullin 5 ubiquitin-protein
      isopeptide ligase. It is currently accepted that this enzyme polyubiquitylates
      A3G on lysine residues, resulting in its degradation by proteasomes. Here, we
      find that A3G without ubiquitylation is still degraded by proteasomes in a Vif
      dependent manner. We further show that Vif is polyubiquitylated and that this
      event could be critical for A3G proteasomal degradation. Thus, A3G is degraded by
      a novel pathway that might involve ubiquitylation of one protein and then targets
      a second binding partner for proteasomal entry and degradation. We propose that
      instead of triggering A3G polyubiquitylation, polyubiquitylated Vif might serve
      as a vehicle to transport A3G into proteasomes for degradation.

PMID- 18326045
TI  - Signaling the signal, cyclic AMP-dependent protein kinase inhibition by insulin
      formed H2O2 and reactivation by thioredoxin.
AB  - Catecholamines in adipose tissue promote lipolysis via cAMP, whereas insulin
      stimulates lipogenesis. Here we show that H(2)O(2) generated by insulin in rat
      adipocytes impaired cAMP-mediated amplification cascade of lipolysis. These
      micromolar concentrations of H(2)O(2) added before cAMP suppressed cAMP
      activation of type IIbeta cyclic AMP-dependent protein kinase (PKA) holoenzyme,
      prevented hormone-sensitive lipase translocation from cytosol to storage
      droplets, and inhibited lipolysis. Similarly, H(2)O(2) impaired activation of
      type IIalpha PKA holoenzyme from bovine heart and from that reconstituted with
      regulatory IIalpha and catalytic alpha subunits. H(2)O(2) was ineffective (a) if
      these PKA holoenzymes were preincubated with cAMP, (b) if added to the catalytic
      alpha subunit, which is active independently of cAMP activation, and (c) if the
      catalytic alpha subunit was substituted by its C199A mutant in the reconstituted
      holoenzyme. H(2)O(2) inhibition of PKA activation remained after H(2)O(2)
      elimination by gel filtration but was reverted with dithiothreitol or with
      thioredoxin reductase plus thioredoxin. Electrophoresis of holoenzyme in SDS gels
      showed separation of catalytic and regulatory subunits after cAMP incubation but
      a single band after H(2)O(2) incubation. These data strongly suggest that
      H(2)O(2) promotes the formation of an intersubunit disulfide bond, impairing cAMP
      dependent PKA activation. Phylogenetic analysis showed that Cys-97 is conserved
      only in type II regulatory subunits and not in type I regulatory subunits; hence,
      the redox regulation mechanism described is restricted to type II PKA-expressing
      tissues. In conclusion, phylogenetic analysis results, selective chemical
      behavior, and the privileged position in holoenzyme lead us to suggest that Cys
      97 in regulatory IIalpha or IIbeta subunits is the residue forming the disulfide
      bond with Cys-199 in the PKA catalytic alpha subunit. A new molecular point for
      cross-talk among heterologous signal transduction pathways is demonstrated.

PMID- 18326046
TI  - Three-dimensional reconstruction of a membrane-bending complex: the RC-LH1-PufX
      core dimer of Rhodobacter sphaeroides.
AB  - A three-dimensional model of the dimeric reaction center-light harvesting I-PufX
      (RC-LH1-PufX) complex from Rhodobacter sphaeroides, calculated from electron
      microscope single particle analysis of negatively stained complexes, shows that
      the two halves of the dimer molecule incline toward each other on the periplasmic
      side, creating a remarkable V-shaped structure. The distribution of negative
      stain is consistent with loose packing of the LH1 ring near the 14th LH1
      alpha/beta pair, which could facilitate the migration of quinone and quinol
      molecules across the LH1 boundary. The three-dimensional model encloses a space
      near the reaction center Q(B) site and the 14th LH1 alpha/beta pair, which is
      approximately 20 angstroms in diameter, sufficient to sequester a quinone pool.
      Helical arrays of dimers were used to construct a three-dimensional membrane
      model, which matches the packing lattice deduced from electron microscope
      analysis of the tubular dimer-only membranes found in mutants of Rba. sphaeroides
      lacking the LH2 complex. The intrinsic curvature of the dimer explains the shape
      and approximately 70-nm diameter of these membrane tubules, and at least
      partially accounts for the spherical membrane invaginations found in wild-type
      Rba. sphaeroides. A model of dimer aggregation and membrane curvature in these
      spherical membrane invaginations is presented.

PMID- 18326047
TI  - A2E, a pigment of the lipofuscin of retinal pigment epithelial cells, is an
      endogenous ligand for retinoic acid receptor.
AB  - Lipofuscin contains fluorophores, which represent a biomarker for cellular aging.
      Although it remains unsubstantiated clinically, experimental results support that
      the accumulation of lipofuscin is related to an increased risk of choroidal
      neovascularization due to age-related macular degeneration, a leading cause of
      legal blindness. Here, we report that a major lipofuscin component, A2E,
      activates the retinoic acid receptor (RAR). In vitro experiments using luciferase
      reporter assay, competitional binding assay, analysis of target genes, and
      chromatin immunoprecipitation (ChIP) assay strongly suggest that A2E is a bona
      fide ligand for RAR and induces sustained activation of RAR target genes. A2E
      induced vascular endothelial growth factor (VEGF) expression in a human retinal
      pigment epithelial cell line (ARPE-19) and RAR antagonist blocked the up
      regulation of VEGF. The conditioned medium of A2E-treated ARPE-19 cells induced
      tube formation in human umbilical vascular endothelial cells, which was blocked
      by the RAR antagonist and anti-VEGF antibody. These results suggest that A2E
      accumulation results in the phenotypic alteration of retinal pigment epithelial
      cells, predisposing the environment to choroidal neovascularization development.
      This is mediated through the agonistic function of A2E, at least in part. The
      results of this study provide a novel potential therapeutic target for this
      incurable condition.

PMID- 18326048
TI  - A protective role for the human SMG-1 kinase against tumor necrosis factor-alpha
      induced apoptosis.
AB  - The human suppressor of morphogenesis in genitalia-1 (hSMG-1) protein kinase
      plays dual roles in mRNA surveillance and genotoxic stress response pathways in
      human cells. Here, we report that small interfering RNA-mediated depletion of
      hSMG-1, but not ATM, ATR, hUpf1, or hUpf2, in human U2OS osteosarcoma cells
      markedly increases the magnitude and accelerates the rate of apoptosis induced by
      tumor necrosis factor-alpha (TNFalpha) stimulation. The increase in TNFalpha
      mediated cell killing observed in hSMG-1-depleted cells is not related to the
      suppression of nonsense-mediated mRNA decay or to the inhibition of TNFalpha
      induced NF-kappaB activation. Rather, we observed that loss of hSMG-1 accelerates
      the degradation of the long form of the FLICE-inhibitory protein (FLIP(L)), an
      inhibitor of death-inducing signaling complex-mediated caspase-8 activation, in
      TNFalpha-treated cells. These results suggest that hSMG-1 plays an important role
      in cell survival during TNFalpha-induced stress.

PMID- 18326049
TI  - Creation and implementation of a pressure ulcer prevention bundle improves
      patient outcomes.
AB  - BACKGROUND: Increased pressure ulcer prevalence and incidence rates led to the
      development of a pressure ulcer prevention program. OBJECTIVES: To decrease
      pressure ulcer rates below national levels by implementing strategies to improve
      patient outcomes. METHODS: Patients admitted to the Stony Brook University
      Medical Center (SBUMC) are assessed for placement in the pressure ulcer
      prevention program. The central element of the program is an evidence-based
      Pressure Ulcer Prevention Bundle using the "Bundle" concept from the Institute
      for Healthcare Improvement. RESULTS: The March 2006 Prevalence and Incidence
      Benchmarking Study demonstrates not only a decrease in institutional prevalence
      and incidence rates but also places SBUMC rates below last year's national
      benchmark rates. CONCLUSION: The implementation of a pressure ulcer prevention
      program has decreased prevalence and incidence rates at SBUMC and improved the
      quality of patient care.

PMID- 18326050
TI  - In vivo inhibition of serine protease processing requires a high fractional
      inhibition of cathepsin C.
AB  - Inhibition of cathepsin C, a dipeptidyl peptidase that activates many serine
      proteases, represents an attractive therapeutic strategy for inflammatory
      diseases with a high neutrophil burden. We recently showed the feasibility of
      blocking the activation of neutrophil elastase, cathepsin G, and proteinase-3
      with a single cathepsin C selective inhibitor in cultured cells. Here we measured
      the fractional inhibition of cathepsin C that is required for blockade of
      downstream serine protease processing, in cell-based assays and in vivo. Using a
      radiolabeled active site probe and U937 cells, a 50% reduction of cathepsin G
      processing required approximately 50% of cathepsin C active sites to be occupied
      by an inhibitor. In EcoM-G cells, inhibition of 50% of neutrophil elastase
      activity required approximately 80% occupancy. Both of these serine proteases
      were fully inhibited at full cathepsin C active site occupancy, whereas granzyme
      B processing in TALL-104 cells was partially inhibited, despite complete
      occupancy. In vivo, leukocytes from cathepsin C(+/-) mice exhibited comparable
      levels of neutrophil elastase activity to wild-type animals, even though their
      cathepsin C activity was reduced by half. The long-term administration of a
      cathepsin C inhibitor to rats, at doses that resulted in the nearly complete
      blockade of cathepsin C active sites in bone marrow, caused significant
      reductions of neutrophil elastase, cathepsin G and proteinase-3 activities. Our
      results demonstrate that the inhibition of cathepsin C leads to a decrease of
      activity of multiple serine proteases involved in inflammation but also suggest
      that high fractional inhibition is necessary to reach therapeutically significant
      effects.

PMID- 18326051
TI  - Combined targeting of epidermal growth factor receptor, signal transducer and
      activator of transcription-3, and Bcl-X(L) enhances antitumor effects in squamous
      cell carcinoma of the head and neck.
AB  - Squamous cell carcinoma of the head and neck (SCCHN) is a leading cause of cancer
      deaths worldwide. Epidermal growth factor receptor (EGFR), an upstream mediator
      of signal transducer and activator of transcription (STAT)-3 is overexpressed in
      a variety of cancers, including SCCHN. Therapies such as monoclonal antibodies
      and tyrosine kinase inhibitors targeting EGFR have demonstrated limited antitumor
      efficacy, which may be explained, in part, by persistent STAT3 activation despite
      EGFR inhibition. STAT3 activation induces expression of target genes in SCCHN,
      including Bcl-X(L), a mediator of antiapoptotic activity. Bcl-X(L) is commonly
      overexpressed in SCCHN where it correlates with chemoresistance, making it a
      potential therapeutic target. Targeting the EGFR-STAT3-Bcl-X(L) pathway at
      several levels, including the upstream receptor, the intracellular transcription
      factor, and the downstream target gene, has not been investigated previously.
      Using erlotinib, an EGFR-specific reversible tyrosine kinase inhibitor in
      combination with a STAT3 transcription factor decoy, we found enhanced antitumor
      effects in vitro and in vivo. The combination of the STAT3 decoy and gossypol, a
      small molecule targeting Bcl-X(L), also yielded enhanced inhibition of cell
      proliferation. The triple combination of erlotinib, STAT3 decoy, and gossypol
      further enhanced cell growth inhibition and apoptosis in vitro, and it down
      regulated signaling molecules further downstream of the EGFR-STAT3 signaling
      pathway, such as cyclin D1. These results suggest that combined targeting of
      several components of an oncogenic signaling pathway may be an effective
      therapeutic strategy for SCCHN.

PMID- 18326052
TI  - Protease-activated receptor-1 mediates thrombin-induced persistent sodium current
      in human cardiomyocytes.
AB  - After the thrombus formation in cardiac cavities or coronaries, the serine
      protease thrombin is produced and can therefore reach the myocardial tissue by
      the active process of extravasation and binds to the G protein-coupled protease
      activated receptor-1 (PAR1) expressed in human myocardium. The role of PAR1 was
      investigated in the thrombin effect on sodium current (I(Na)). I(Na) was recorded
      in freshly isolated human atrial myocytes by the whole-cell patch-clamp method.
      Action potentials (AP) were recorded in guinea pig ventricular tissue by the
      conventional glass microelectrode technique. Thrombin-activated PAR1 induced a
      tetrodotoxin-blocked persistent sodium current, I(NaP), in a concentration
      dependent manner with an apparent EC(50) of 28 U/ml. The PAR1 agonist peptide
      SFLLR-NH(2) (50 microM) was able to mimic PAR1-thrombin action, whereas PAR1
      antagonists N(3)-cyclopropyl-7-((4-(1-methylethyl)-phenyl)methyl)-7H-pyrrolo(3,2
      f)quinazoline-1,3-diamine (SCH 203099; 10 microM) and 1-(3,5-di-tert-butyl-4
      hydroxy-phenyl)-2-[3-(3-ethyl-3-hydroxy-pentyl)-2-imino-2,3-dihydro-imidazol-1
      yl]-ethanone (ER 112787) (1 microM), completely inhibited it. The activated PAR1
      involves the calcium-independent phospholipase-A(2) signaling pathway because two
      inhibitors of this cascade, bromoenol lactone (50 microM) and haloenol lactone
      suicide substrate (50 microM), block PAR1-thrombin-induced I(NaP).Asa consequence
      of I(NaP) activation, in guinea pig right ventricle papillary muscle, action
      potential duration (APD) were significantly increased by 20% and 15% under the
      respective action of 32 U/ml thrombin and 50 microM SFLLR-NH(2), and these
      increases in APD were prevented by 1 microM tetrodotoxin or markedly reduced by
      application of 1 microM SCH 203099 or ER 112787. Thrombin, through PAR1
      activation, increases persistent component of the Na(+) current resulting in an
      uncontrolled sodium influx into the cardiomyocyte, which can contribute to
      cellular injuries observed during cardiac ischemia.

PMID- 18326053
TI  - Ecodevelopmental x intrapersonal risk: substance use and sexual behavior in
      Hispanic adolescents.
AB  - Hispanic adolescents are a rapidly growing population and are highly vulnerable
      to substance abuse and HIV infection. Many interventions implemented thus far
      have been "one size fits all" models that deliver the same dosage and sequence of
      modules to all participants. To more effectively prevent substance use and HIV in
      Hispanic adolescents, different risk profiles must be considered. This study's
      purpose is to use intrapersonal and ecodevelopmental risk processes to identify
      Hispanic adolescent subgroups and to compare substance use rates and sexual
      behavior by risk subgroup. The results indicate that a larger proportion with
      high ecodevelopmental risk (irrespective of the intrapersonal risk for substance
      use) report lifetime and past 90-day cigarette and illicit drug use. In contrast,
      a larger proportion with high intrapersonal risk for unsafe sex (irrespective of
      ecodevelopmental risk) report early sex initiation and sexually transmitted
      disease incidence. Implications for intervention development are discussed in
      terms of these Hispanic adolescent subgroups.

PMID- 18326055
TI  - Reproducibility and minimal detectable change of three-dimensional kinematic
      analysis of reaching tasks in people with hemiparesis after stroke.
AB  - BACKGROUND AND PURPOSE: Three-dimensional kinematic analysis of reaching has
      emerged as an evaluative measure of upper-extremity motor performance in people
      after stroke. However, the psychometric properties supporting the use of
      kinematic data for evaluating longitudinal change in motor performance have not
      been established. The objective of this study was to determine, in a test-retest
      reliability manner, the reproducibility and minimal detectable change for
      reaching kinematics in people after stroke. SUBJECTS AND METHODS: Fourteen
      participants with hemiparesis after stroke performed forward reaching tasks on 2
      occasions 37.3 (SD=9.8) days apart. At each session, participants performed 4
      forward reaching tasks produced by the combination of 2 target heights (low and
      high [109 and 153 cm from the floor, respectively]) and 2 instructed movement
      speeds (self-selected and as fast as possible). Two analytical methods were used
      to calculate kinematic parameters. RESULTS: Relative reliability (intraclass
      correlation coefficient) ranged from .04 to .99, and absolute reliability
      (standard error of measurement) ranged from 2.7% to 76.8%, depending on the
      kinematic variable, the demands of the motor task (target height and movement
      speed), and the analytical method. Bland-Altman analysis, a statistical method
      used to assess the repeatability of a method, revealed few systematic errors
      between sessions. The minimal detectable change ranged from 7.4% to 98.9%.
      DISCUSSION AND CONCLUSION: Depending on the demands of the motor task and the
      analytical method, most kinematic outcome measures (such as peak hand velocity,
      endpoint error, reach extent, maximum shoulder flexion range of motion, and
      minimum elbow extension range of motion) are reliable measures of motor
      performance in people after stroke. However, because of the magnitude of within
      subject measurement error, some variables (such as peak hand velocity, time to
      peak hand velocity, and movement time) must change considerably (>50%) to
      indicate a real change in individual participants. The results of our reliability
      analysis, which are based on our cohort of participants with hemiparesis after
      stroke and our specific paradigm, may not be generalizable to different
      subpopulations of people with hemiparesis after stroke or to the myriad movement
      tasks and kinematic variables used for the assessment of reaching performance in
      people after stroke.

PMID- 18326054
TI  - Locomotor training restores walking in a nonambulatory child with chronic,
      severe, incomplete cervical spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Locomotor training (LT) enhances walking in adult
      experimental animals and humans with mild-to-moderate spinal cord injuries
      (SCIs). The animal literature suggests that the effects of LT may be greater on
      an immature nervous system than on a mature nervous system. The purpose of this
      study was to evaluate the effects of LT in a child with chronic, incomplete SCI.
      SUBJECT: The subject was a nonambulatory 4 1/2-year-old boy with an American
      Spinal Injury Association Impairment Scale (AIS) C Lower Extremity Motor Score
      (LEMS) of 4/50 who was deemed permanently wheelchair-dependent and was enrolled
      in an LT program 16 months after a severe cervical SCI. METHODS: A pretest
      posttest design was used in the study. Over 16 weeks, the child received 76 LT
      sessions using both treadmill and over-ground settings in which graded sensory
      cues were provided. The outcome measures were ASIA Impairment Scale score, gait
      speed, walking independence, and number of steps. RESULT: One month into LT,
      voluntary stepping began, and the child progressed from having no ability to use
      his legs to community ambulation with a rolling walker. By the end of LT, his
      walking independence score had increased from 0 to 13/20, despite no change in
      LEMS. The child's final self-selected gait speed was 0.29 m/s, with an average of
      2,488 community-based steps per day and a maximum speed of 0.48 m/s. He then
      attended kindergarten using a walker full-time. DISCUSSION AND CONCLUSION: A
      simple, context-dependent stepping pattern sufficient for community ambulation
      was recovered in the absence of substantial voluntary isolated lower-extremity
      movement in a child with chronic, severe SCI. These novel data suggest that some
      children with severe, incomplete SCI may recover community ambulation after
      undergoing LT and that the LEMS cannot identify this subpopulation.

PMID- 18326056
TI  - Pediatric physical therapists' perceptions of their training in assistive
      technology.
AB  - BACKGROUND AND PURPOSE: Availability of assistive technology (AT) and federal
      legislation promoting greater use of AT for children with disabilities have
      increased substantially. The purpose of this study was to determine the perceived
      adequacy of previous training in AT, specific training needs, preferred methods
      of training, and the confidence level of pediatric physical therapists in
      providing AT. SUBJECTS AND METHODS: Three hundred eighty pediatric physical
      therapists responded to a survey questionnaire mailed to a random sample of
      members of the Section on Pediatrics of the American Physical Therapy
      Association. The survey was used to determine training needs of therapists in the
      area of AT, their confidence in delivering AT services, preferred methods of
      training, and challenges in becoming trained. RESULTS: The therapists reported
      having less-than-adequate training in AT and a lack of confidence in delivering
      AT services. They also reported that they would like accessible and affordable
      training that focuses on funding technology and services, knowledge of specific
      devices, and assessment and evaluation methods. DISCUSSION AND CONCLUSION: The
      findings underscore the need to develop pre-service, in-service, and continuing
      education training opportunities in AT for providers working with children who
      have disabilities.

PMID- 18326057
TI  - Clinical assessment of motor imagery after stroke.
AB  - OBJECTIVE: The aim of this study was to investigate: (1) the effects of a stroke
      on motor imagery vividness as measured by the Kinesthetic and Visual Imagery
      Questionnaire (KVIQ-20); (2) the influence of the lesion side; and (3) the
      symmetry of motor imagery. METHODS: Thirty-two persons who had sustained a
      stroke, in the right (n = 19) or left (n = 13) cerebral hemisphere, and 32 age
      matched healthy persons participated. The KVIQ-20 assesses on a 5-point ordinal
      scale the clarity of the image (visual scale) and the intensity of the sensations
      (kinesthetic scale) that the subjects are able to imagine from the first-person
      perspective. RESULTS: In both groups, the visual scores were higher (P = .0001)
      than the kinesthetic scores and there was no group difference. Likewise, visual
      scores remained higher than kinesthetic scores irrespective of the lesion side.
      The visual scores poststroke were higher (P = .001) when imagining upper limb
      movements on the unaffected side than those on the affected side. When focusing
      on the lower limb only, however, the kinesthetic scores were higher (P = .001)
      when imagining movements of the unaffected compared to those on the affected
      side. CONCLUSIONS: The vividness of motor imagery poststroke remains similar to
      that of age-matched healthy persons and is not affected by the side of the
      lesion. However, after stroke motor imagery is not symmetrical and motor imagery
      vividness is better when imagining movements on the unaffected than on the
      affected side, indicating an overestimation possibly related to a hemispheric
      imbalance or a recalibration of motor imagery perception.

PMID- 18326058
TI  - Prevalence of periodontal pathogens in subgingival lesions, atherosclerotic
      plaques and healthy blood vessels: a preliminary study.
AB  - BACKGROUND AND OBJECTIVE: Previous studies have reported different periodontal
      bacteria in atherosclerotic lesions, but their involvement in plaque formation
      remains unclear. The aim of the present study was to investigate the presence of
      20 periodontal bacteria in atherosclerotic samples and healthy blood vessels
      (used as controls) and to clarify their relationship in regard to clinical and
      bacteriological periodontal status. MATERIAL AND METHODS: The day before vascular
      surgery the patients had a thorough periodontal examination and bacteriological
      samples were taken from periodontally diseased sites. Atheromatous plaques,
      internal mammary arteries and saphenous veins were harvested during surgery. A
      DNA-DNA hybridization procedure was used to screen periodontal and vascular
      samples for the 20 selected bacterial species. RESULTS: Periodontal samples from
      the severe periodontitis group were found to have a higher prevalence and biomass
      of bacterial species than the moderate periodontitis group. In vessel samples,
      the prevalence of the same 20 bacterial species analyzed together was similar in
      the two groups, except for saphenous veins. CONCLUSION: The presence of
      periodontal pathogens in atherosclerotic plaques and in apparently healthy
      vessels appeared to reflect a higher level of bacteremia rather than infection of
      endothelial cells.

PMID- 18326059
TI  - The many faces of MRSA: community-acquired infection knows no bounds.

PMID- 18326060
TI  - The graying of America: the impact of aging baby boomers on emergency
      departments.

PMID- 18326061
TI  - Comments on effects of pet insurance on the veterinary profession.

PMID- 18326062
TI  - Fat grafting to the breast revisited: safety and efficacy.

PMID- 18326063
TI  - Fat grafting to the breast revisited: safety and efficacy.

PMID- 18326064
TI  - Fat grafting to the breast.

PMID- 18326065
TI  - The double-opposing periareolar flap: a novel concept for nipple-areola
      reconstruction.

PMID- 18326066
TI  - Nipple-areola reconstruction: technical improvements.

PMID- 18326067
TI  - Meta-analysis of small trials: proceed with caution.

PMID- 18326068
TI  - [Should first responder place laryngeal mask airways  to initiate basic CPR?].

PMID- 18326069
TI  - Bibliography. Current world literature. Lipids.

PMID- 18326070
TI  - 1-(1-Arylethylidene)thiosemicarbazide derivatives: a new class of tyrosinase
      inhibitors.
AB  - A series of 1-(1-arylethylidene)thiosemicarbazide compounds and their analogues
      were synthesized and characterized by 1H NMR, MS. Their tyrosinase inhibitory
      activities were investigated by an assay based on the catalyzing ability of
      tyrosinase for the oxidation of L-DOPA, comparing with 4-methoxycinnamic acid and
      arbutin. The results showed that (1) all the synthesized compounds could perform
      a significant inhibitory activity for tyrosinase; (2) for these compounds, the
      main active moiety interacting with the center of tyrosinase would be
      thiosemicarbazo group; (3) the inhibitory activity was close related with
      thiosemicarbazide moieties and the groups attached on the aromatic ring.

PMID- 18326071
TI  - Bladder neck contracture after robot-assisted laparoscopic radical prostatectomy:
      evaluation of incidence and risk factors and impact on urinary function.
AB  - BACKGROUND AND PURPOSE: Bladder neck contracture (BNC) after radical
      prostatectomy has been reported to occur in 5% to 32% of men after open
      retropubic prostatectomy (RRP) and in 0% to 3% after laparoscopic RRP. Optimal
      anastomotic closure involves creating a watertight, tension-free anastomosis with
      well-vascularized, mucosal apposition and correct realignment of the urethra. The
      cause of BNC is poorly understood; however, it is likely related to multiple
      factors, including excessive luminal narrowing at the site of reconstruction,
      local tissue ischemia, failed mucosal apposition, and urinary leakage. In this
      large series of patients who underwent robot-assisted laparoscopic radical
      prostatectomy (RLRP), we report the incidence of BNC, evaluate the influence of
      age, body mass index (BMI), estimated blood loss (EBL), surgical time, and
      prostate weight on its development and assess follow-up urinary function.
      METHODS: Between February 2003 and July 2006, 650 consecutive men underwent RLRP
      at our institution. Patients with aborted or open conversion procedures were
      excluded from analysis. The mean overall follow-up for the remaining 634 patients
      was 19.5 months. Patients presenting with symptoms of outlet obstruction were
      evaluated with cystoscopy to confirm a BNC. Comparisons of age, BMI, EBL,
      operative time, and prostate weight were performed using the Student t-test and
      chi-square analysis. RESULTS: BNC was the diagnosis in seven patients (1.1%) with
      a mean time of presentation of 4.8 (3-12) months postoperatively. The BNC
      patients had comparable mean age, BMI, prostate weight, and EBL to the non-BNC
      cohort. Their operative time, however, was significantly longer (283 v 225 min.,
      P = 0.04). CONCLUSIONS: The incidence of BNC after radical prostatectomy is 2.2%
      in a large series of men undergoing RLRP. The diagnosis was made within 1 year.
      No significant impact on urinary continence or quality-of-life urinary function
      was observed after BNC management. A running anastomosis, better visualization,
      improved instrument maneuverability, and decreased blood loss may account for
      such a low rate.

PMID- 18326072
TI  - Testicular chromosome structure and gene expression. Proceedings to the XIXth
      North American Testis Workshop. April 18-20, 2007. Tampa, Florida, USA.

PMID- 18326073
TI  - Linear plasmids in plant mitochondria: peaceful coexistences or malicious
      invasions?
AB  - Plant mitochondria contain small extrachromosomal DNAs in addition to a large and
      complex main mitochondrial genome. These molecules can be regarded as
      extrachromosomal replicons or plasmids, of which there are two forms, circular
      and linear. Linear mitochondrial plasmids are present in many fungi and in some
      plants, but they seem to be absent from most animal cells. They usually have a
      common structural feature, called an invertron, that is characterized by the
      presence of terminal inverted repeats and proteins covalently attached to their 5
      termini. Linear mitochondrial plasmids possess one to six ORFs that can encode
      unknown proteins but often code for the DNA and RNA polymerases. Although the
      functions of most linear plasmids in plant mitochondria are unknown, some
      plasmids may be associated with mitochondrial genome rearrangements and may have
      phenotypic effects due to their integration into mitochondrial genome. The
      Brassica 11.6-kb plasmid, one of the linear mitochondrial plasmids in plants,
      shows a non-maternal inheritance, in contrast to mitochondrial genomes. The
      origin of these plasmids is still a mystery, but indirect evidence indicates the
      possibility of horizontal transfer from fungal mitochondria. In this review, the
      main features of these unique DNAs present in plant mitochondria are described.

PMID- 18326074
TI  - Proceedings of the XVII International Roundtable. September 3-7, 2006. Bern,
      Switzerland.

PMID- 18326075
TI  - The process of RNA editing in plant mitochondria.
AB  - RNA editing changes more than 400 cytidines to uridines in the mRNAs of
      mitochondria in flowering plants. In other plants such as ferns and mosses, RNA
      editing reactions changing C to U and U to C are observed at almost equal
      frequencies. Development of transfection systems with isolated mitochondria and
      of in vitro systems with extracts from mitochondria has considerably improved our
      understanding of the recognition of specific editing sites in the last few years.
      These assays have also yielded information about the biochemical parameters, but
      the enzymes involved have not yet been identified. Here we summarize our present
      understanding of the process of RNA editing in flowering plant mitochondria.

PMID- 18326076
TI  - Eltrombopag in thrombocytopenia.

PMID- 18326077
TI  - Treatment of head and neck cancer.

PMID- 18326078
TI  - Treatment of head and neck cancer.

PMID- 18326079
TI  - Treatment of head and neck cancer.

PMID- 18326080
TI  - Proceedings of the 2007 Workshop on Radiation and Multidrug Resistance Mediated
      via the Tumor-Microenvironment. February 12-13, 2007. Dresden, Germany.

PMID- 18326081
TI  - Proceedings of the Fifth Genoa Meeting on Hypertension, Diabetes and Renal
      Disease. February 23-25, 2006. Genoa, Italy.

PMID- 18326082
TI  - Apolipoprotein E Arg136 --> Cys mutation and hyperlipidemia in a large central
      European population sample.

PMID- 18326083
TI  - [Picture of the month: intracranial gas].

PMID- 18326084
TI  - [Serious debate on unconventional treatment, thank you].

PMID- 18326086
TI  - What causes fibrosis progression in recurrent hepatitis C?

PMID- 18326085
TI  - Monocyte chemoattractant protein-1 is a pathogenic component in a model for a
      hereditary peripheral neuropathy.
AB  - Macrophages are critically involved in the pathogenesis of genetically caused
      demyelination, as it occurs in models for inherited demyelinating neuropathies.
      It is presently unknown which factors link the Schwann cell-based myelin mutation
      to the activation of endoneurial macrophages. Here we identified the chemokine
      monocyte chemoattractant protein-1 (MCP-1) as a first and crucial factor
      upregulated in Schwann cells of mice heterozygously deficient for the myelin
      protein zero. The chemokine could be identified as an important mediator of
      macrophage immigration into peripheral nerves. Furthermore, a 50% reduction of
      chemokine expression by crossbreeding with MCP-1-deficient mice reduced the
      increase in macrophage numbers in the mutant nerves and lead to a robust
      amelioration of pathology. Surprisingly, the complete absence of MCP-1 aggravated
      the disease. Our findings show that reducing but not eliminating chemokine
      expression can rescue genetically caused demyelination that may be an interesting
      target in treating demyelinating diseases of the peripheral nervous system.

PMID- 18326087
TI  - Liver function determines success of transjugular intrahepatic portosystemic
      shunt in treating hepatic hydrothorax.

PMID- 18326088
TI  - Intraoperative hyperglycemia and liver transplant survival.

PMID- 18326089
TI  - New drug information. Combigan.

PMID- 18326090
TI  - The circumpolar health movement comes full circle.
AB  - OBJECTIVES: Evaluate the course of the International Congress(es) on Circumpolar
      Health (ICCH) and the Circumpolar movement in the context of concomitant
      historical events. Make recommendations for future Circumpolar health research.
      STUDY DESIGN: MEDLINE search and historical archive search of ICCH proceedings.
      METHODS: Search of all PubMed resources from 1966 concerning the Circumpolar
      health movement. Two University of Alaska Anchorage archive collections were
      searched: the C. E. Albrecht and Frank Pauls Archive Collections. RESULTS: Eleven
      sets of proceedings manuscripts and one set of proceedings abstracts were
      evaluated. There was a trend toward consistent use of existing journals with
      indexing in Index Medicus; shorter intervals between the Congress and proceedings
      manuscript publication; and increased online availability of either the table of
      contents or proceedings citations. Recent additions include online publication of
      full length manuscripts and two instances of full peer review evaluations of the
      proceedings manuscripts. These trends in proceedings publication are described
      within the course of significant events in the Circumpolar health movement.
      CONCLUSIONS: There has been a trend toward more rapid dissemination of scientific
      content, more analytic documentation of epidemiologic study design, and a trend
      toward wider dissemination of scientific content through the Internet.
      Significant progress in each of those areas is still possible and desirable.

PMID- 18326091
TI  - Peer to peer.

PMID- 18326092
TI  - Oh wondrous web?

PMID- 18326093
TI  - Talking horses.

PMID- 18326094
TI  - Doing the right thing.

PMID- 18326095
TI  - We need to take account of the reality of the social oppression that hinders
      individual recovery journeys.

PMID- 18326096
TI  - Beware the oft forgotten Non-Dependant Deduction--it can place parents in
      poverty.

PMID- 18326097
TI  - Learning the lessons together.

PMID- 18326098
TI  - A new option for hospital discharge.

PMID- 18326099
TI  - Towards recovery competencies.

PMID- 18326100
TI  - Listen to our voices.

PMID- 18326101
TI  - Meeting the race equality challenge.

PMID- 18326102
TI  - Network.

PMID- 18326103
TI  - Is there a better way to ask patients whether there is "anything else"?

PMID- 18326104
TI  - Does CPAP for mild sleep apnea lower the risk of cardiovascular events?

PMID- 18326105
TI  - Are antibiotics or nasal steroids effective for acute sinusitis?

PMID- 18326106
TI  - Spondylolisthesis and spondylolysis.

PMID- 18326107
TI  - [Comments on the paper: Status and drug resistance surveillance of enterococcus
      infection in patients with severe hepatitis].

PMID- 18326108
TI  - Housing the poor in a colonial city: the Bombay Improvement Trust, 1898-1918.

PMID- 18326109
TI  - Outbreak news. Ebola haemorrhagic fever,  Uganda--end of the  outbreak.

PMID- 18326110
TI  - Outbreak news. Meningococcal disease in the African  meningitis belt.

PMID- 18326111
TI  - Enterotoxigenic Escherichia coli:  advances in technical and laboratory  aspects
      of research and development  of vaccines.

PMID- 18326113
TI  - [Guidelines in cardiac pacing and resynchronization therapy].

PMID- 18326115
TI  - "Irrepressible chirpy Cockney chappies"? Humour as an aid to survival.

PMID- 18326117
TI  - Mirroring societies at war: pictorial humour in the British and French popular
      press during the First World War.

PMID- 18326118
TI  - Laughter and tears in the Great War: the need for laughter/the guilt of humour.

PMID- 18326120
TI  - Homosexuality and the British Army during the First World War.

PMID- 18326121
TI  - Jacob's heritage: racial inheritance in British imperial identity, 1870-1918.

PMID- 18326122
TI  - [Commentary to the articles: Kaplan NM. Vascular outcome in type 2 diabetes: an
      ADVANCE? Lancet 2007; 370:804-5; Patel A; ADVANCE Collaborative Group, MacMahon
      S, Chalmers J, Neal B i wsp. Effects of a fixed combination of perindopril and
      indapamide on macrovascular and microvascular outcomes in patients with type 2
      diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet
      2007; 370:829-40].

PMID- 18326123
TI  - Implementing an expressive writing study in a cancer clinic.
AB  - Patients at a comprehensive cancer center have participated in a weekly writing
      program for 7 years. Anecdotal evidence following writing in this clinical
      setting appeared congruent with the results of expressive writing studies
      conducted in laboratory settings. To move expressive writing research beyond the
      laboratory, we evaluated the feasibility of engaging a clinical population in a
      structured expressive writing task while they waited for an appointment in a
      cancer clinic. Adult leukemia and lymphoma patients (n = 71) completed a baseline
      assessment, 20-minute writing task, postwriting assessment, and 3-week follow-up;
      88% completed the writing task and 56% completed the follow-up. Participants
      reported positive responses to the writing, and immediately postwriting about
      half (49.1%) reported that writing resulted in changes in their thoughts about
      their illness, while 53.8% reported changes in their thoughts at the 3-week
      follow-up. Reports of changes in thoughts about illness immediately postwriting
      were significantly associated with better physical quality of life at follow-up,
      controlling for baseline quality of life. Initial qualitative analyses of the
      texts identified themes related to experiences of positive change/transformation
      following a cancer diagnosis. Findings support the feasibility of conducting
      expressive writing with a clinical population in a nonlaboratory setting. Cancer
      patients were receptive to expressive writing and reported changes in the way
      they thought about their illness following writing. These preliminary findings
      indicate that a single, brief writing exercise is related to cancer patients'
      reports of improved quality of life.

PMID- 18326124
TI  - [On 300th anniversary of The Moscow Medico-surgical school -- the forerunner of
      the systematic higher medical education in Russia].

PMID- 18326125
TI  - Anaesthesia societies: their global responsibilities.

PMID- 18326126
TI  - Computerised tomography for the detection of pulmonary emboli in intensive care
      patients--a retrospective cohort study.
AB  - Pulmonary emboli are frequently considered as a cause for respiratory
      deterioration in intensive care unit (ICU) patients, however empirical
      observation suggests that computerised tomographic (CT) angiography is
      infrequently positive after the first 24 hours. This study aimed to determine the
      rate and risk factors for detection of pulmonary emboli by CT angiography in ICU
      patients. All patients undergoing CT angiography > 24 hours after ICU admission
      for respiratory deterioration from April 2000 until January 2004 were included.
      The positivity rate for pulmonary emboli was determined and risk factors
      analysed. Seven (6%) out of 113 CT angiograms were positive for pulmonary emboli.
      All were found in trauma patients. Comparing positive to negative scans,
      predefined risk factors including head injury (5/7 positive scans, 71% vs. 23/106
      negative scans, 22%, P = 0.005), spine injury with neurological impairment (4/7,
      57% vs. 9/106, 8%, P = 0.002) and lower limb injury (3/7, 43% vs. 12/106, 9%, P =
      0.039) were significantly more frequent in patients with positive scans. Deep
      vein thrombosis prophylaxis was employed less frequently prior to a positive scan
      (in 3/7, 43% patients with positive scans vs. 91/106, 86% patients with negative
      scans P = 0.015). Only the predefined risk factors were independently associated
      with positive CT angiography on limited logistic regression (OR 24.7 per risk
      factor, 95% CI 2.38 to 255.1, P = 0.007). Pulmonary emboli were infrequently
      diagnosed using CT angiography in ICU patients admitted for more than 24 hours
      and found only in patients with recognised risk factors.

PMID- 18326127
TI  - Hospital and 28-day mortality amongst 'high risk' surgical patients. A
      retrospective cohort study.
AB  - The likely mortality benefit from pre-optimisation of high risk surgical patients
      depends on the baseline risk of death. The baseline risk estimated from the
      control groups of studies of pre-optimisation may not reflect the risk in other
      institutions. We determined the 28-day mortality of 'high risk' adult surgical
      patients in our institution by performing a retrospective cohort study of 554
      patients undergoing major or ultra-major general or vascular surgery lasting more
      than two hours. Patients were identified as being high risk based on the presence
      of risk factors used in previous studies of pre-optimisation. The 28-day
      mortality (95% CI) was 0% for patients with no risk factors and 2.3 (0.8 to 3.7)%
      for patients with at least one risk factor. These data indicate that the risk of
      death amongst high risk surgical patients may vary considerably between
      institutions.

PMID- 18326128
TI  - Hyperglycaemia upon onset of ICU-acquired bloodstream infection is associated
      with adverse outcome in a mixed ICU population.
AB  - This study aimed to assess whether a relationship exists between hyperglycaemia
      and outcome in a mixed cohort of critically ill patients with nosocomial
      bloodstream infection (BSI), and to evaluate patterns of blood glucose levels
      between survivors and non-survivors. A historical observational cohort study was
      conducted in the intensive care unit (ICU) of a tertiary care referral centre.
      One-hundred-and-thirty patients with a microbiologically documented ICU-acquired
      BSI (period 2003 to 2004) were included. For the study, morning blood glucose
      levels were evaluated from one day prior until five days after onset of BSI. The
      contribution of hyperglycaemia, divided in three subgroups (> or = 150 mg/dl, >
      or = 175 mg/dl and > or = 200 mg/dl), to in-hospital mortality was estimated by
      logistic regression. In-hospital mortality was 36.2%. Over the seven study days,
      no differences were found in daily morning blood glucose levels between survivors
      (n = 83) and non-survivors (n = 47). Nevertheless, the trend of blood glucose
      levels upon onset of BSI showed a remarkable increase in the non-survivors,
      whereas it decreased in the survivors. Hyperglycaemia (> or = 175 mg/dl and > or
      = 200 mg/dl) was observed more often among the non-survivors. Multivariate
      logistic regression showed that APACHE II (P = 0.002), antibiotic resistance (P =
      0.004) and hyperglycaemia (> or = 175 mg/dl) upon onset of BSI (P = 0.017) were
      independently associated with in-hospital mortality, whereas a history of
      diabetes (P = 0.041) was associated with better outcome. Hyperglycaemia (> or =
      175 mg/dl) upon onset of ICU-acquired BSI is associated with worse outcome in a
      heterogeneous ICU population. Patterns of morning blood glucose levels have only
      limited value in the prediction of the individual course.

PMID- 18326129
TI  - The incidence and risk of central venous catheter malpositioning: a prospective
      cohort study in 1619 patients.
AB  - Central venous catheters are used in various hospital wards. An anterior
      posterior chest X-ray is usually obtained soon after cannulation to assess the
      location of the catheter tip. This prospective clinical study was designed to
      determine the radiographic catheter tip position after central venous cannulation
      by various routes, to identify clinical problems possibly associated with the use
      of malpositioned catheters and to make a cost-benefit analysis of routine chest X
      ray with respect to catheter malposition. A total 1619 central venous
      cannulations were recorded during a three-year period with respect to patient
      data, information about the cannulation procedures, the radiographic catheter
      positions and complications during clinical use. The total incidence of
      radiographic catheter tip malposition, defined as extrathoracic or ventricular
      positioning, was 3.3% (confidence interval 25 to 4.3%). Cannulation by the right
      subclavian vein was associated with the highest risk of malposition, 9.1%,
      compared with 1.4% by the right internal jugular vein. Six of the 53
      malpositioned catheters were removed or adjusted. No case of malposition was
      associated with vascular perforation, local venous thrombosis or cerebral
      symptoms. We conclude that the radiographic incidence of central venous catheter
      malpositioning is low and that clinical use of malpositioned catheters is
      associated with few complications. However, determination of the catheter
      position by chest X-ray should be considered when mechanical complications cannot
      be excluded, aspiration of venous blood is not possible, or the catheter is
      intended for central venous pressure monitoring, high flow use or infusion of
      local irritant drugs.

PMID- 18326130
TI  - Bayesian approach to predict hospital mortality of intensive care readmissions
      during the same hospitalisation.
AB  - No specific prognostic model has been developed for patients readmitted to the
      intensive care unit (ICU) during the same hospitalisation. This study assesses
      the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) II
      predicted mortality measured at the time of ICU readmission and whether
      incorporating information prior to the readmission will improve its performance
      to predict hospital mortality of patients readmitted to ICU during the same
      hospitalisation. A total of 602 readmissions during the same hospitalisation
      between 1987 and 2002 were identified. The first admission APACHE II predicted
      mortality was significantly associated with the hospital mortality only in the
      subgroup of patients readmitted within seven days of ICU discharge (odds ratio
      1.16, 95% confidence interval 1.01 to 1.34; P = 0.035). In the subgroups of
      patients readmitted within seven days of discharge, the readmission APACHE II
      predicted mortality was also significantly better than the first admission APACHE
      II predicted mortality in discriminating between survivors and non-survivors
      (area under the receiver operating characteristic curve: 0.785 vs. 0.676, z
      statistic = 2.93; P = 0.003). Incorporating the first admission APACHE II
      predicted mortality to the readmission APACHE II predicted mortality, either by
      multilevel likelihood ratios or logistic regression, did not significantly
      improve its discrimination (area under the receiver operating characteristic
      curve: 0.792 vs. 0.785, z statistic = 0.52; P = 0.603). Our results suggested
      that information on prior ICU admission during the same hospitalisation is not as
      important as the severity of illness measured at the time of readmission in
      determining the mortality of intensive care readmissions during the same
      hospitalisation.

PMID- 18326131
TI  - Prediction of successful defibrillation in human victims of out-of-hospital
      cardiac arrest: a retrospective electrocardiographic analysis.
AB  - In the present study we sought to examine the efficacy of an electrocardiographic
      parameter, 'amplitude spectrum area' (AMSA), to predict the likelihood that any
      one electrical shock would restore a perfusing rhythm during cardiopulmonary
      resuscitation in human victims of out-of-hospital cardiac arrest. AMSA analysis
      is not invalidated by artefacts produced by chest compression and thus it can be
      performed during CPR, avoiding detrimental interruptions of chest compression and
      ventilation. We hypothesised that a threshold value of AMSA could be identified
      as an indicator of successful defibrillation in human victims of cardiac arrest.
      Analysis was performed on a database of electrocardiographic records,
      representing lead 2 equivalent recordings from automated external defibrillators
      including 210 defibrillation attempts from 90 victims of out-of-hospital cardiac
      arrest. A 4.1 second interval of ventricular fibrillation or ventricular
      tachycardia, recorded immediately preceding the delivery of the shock, was
      analysed using the AMSA algorithm. AMSA represents a numerical value based on the
      sum of the magnitude of the weighted frequency spectrum between two and 48 Hz.
      AMSA values were significantly greater in successful defibrillation (restoration
      of a perfusing rhythm), compared to unsuccessful defibrillation (P < 0.0001). An
      AMSA value of 12 mV-Hz was able to predict the success of each defibrillation
      attempt with a sensitivity of 0.91 and a specificity of 0.97. In conclusion, AMSA
      analysis represents a clinically applicable method, which provides a real-time
      prediction of the success of defibrillation attempts. AMSA may minimise the
      delivery of futile and detrimental electrical shocks, reducing thereby post
      resuscitation myocardial injury.

PMID- 18326132
TI  - Pre-existing cardiac disease, troponin I elevation and mortality in patients with
      severe sepsis and septic shock.
AB  - A prospective, observational study was undertaken to determine the frequency of
      troponin I elevation and the incidence of pre-existing cardiac disease in
      patients with severe sepsis and septic shock, and to determine their relationship
      to mortality. The setting was the surgical intensive care unit of a tertiary care
      medical centre. Sixty-six consecutive patients admitted with severe sepsis or
      septic shock requiring pulmonary artery catheterisation for haemodynamic
      monitoring were studied. Measurement of troponin I was done at the time of
      pulmonary artery catheterisation and every six to eight hours if there was
      ongoing tachycardia, hypotension or arrhythmias requiring treatment. Preexisting
      cardiac disease was determined from the patient and/or family members as well as
      from the medical record. Significant cardiac history was defined as prior
      myocardial infarction; abnormal treadmill report, nuclear medicine study or
      coronary angiogram; history of congestive heart failure or arrhythmia requiring
      treatment. Forty-two patients (64%) had elevated troponin I at study entrance and
      23 patients (35%) had pre-existing cardiac disease. History of cardiac disease
      was associated with reduced cardiac index and oxygen delivery, and a nearly three
      fold increase in mortality (44% vs. 16%, P = 0.03), irrespective of elevated
      troponin I levels. Troponin I elevation alone was not associated with increased
      mortality. We conclude that pre-existing cardiac disease and elevated troponin I
      are commonly found in surgical patients with severe sepsis and septic shock. In
      our study, pre-existing cardiac disease, and not troponin I elevation, was
      associated with increased mortality.

PMID- 18326133
TI  - Arterial gas embolism: a review of cases at Prince of Wales Hospital, Sydney,
      1996 to 2006.
AB  - Arterial gas embolism may occur as a complication of diving or certain medical
      procedures. Although relatively rare, the consequences may be disastrous. Recent
      articles in the critical care literature suggest the non-hyperbaric medical
      community may not be aware of the role for hyperbaric oxygen therapy in non
      diving related gas embolism. This review is part of an Australian appraisal of
      experience in the management of arterial gas embolism over the last 10 years. We
      identified all patients referred to Prince of Wales Hospital Department of Diving
      and Hyperbaric Medicine with a diagnosis of arterial gas embolism from 1996 to
      2006. Twenty-six patient records met our selection criteria, eight iatrogenic and
      18 diving related. All patients were treated initially with a 280 kPa compression
      schedule. At discharge six patients were left with residual symptoms. Four were
      left with minor symptoms that did not significantly impact quality of life. Two
      remained severely affected with major neurological injury. Both had non-diving
      related arterial gas embolism. There was a good outcome in the majority of
      patients who presented with arterial gas embolism and were treated with
      compression.

PMID- 18326134
TI  - The influence of passive leg elevation on the cross-sectional area of the
      internal jugular vein and the subclavian vein in awake adults.
AB  - The aim of this study was to evaluate the influence of passive leg elevation and
      Trendelenburg position on the cross-sectional area (CSA) of the internal jugular
      (II) and subclavian veins (SCV). Ultrasound imaging was used for the following
      measurements of both the IJV and SCV baseline in the supine position (control);
      Trendelenburg position 15 degrees; reverse Trendelenburg position 15 degrees and
      passive leg elevation 50 degrees. Twenty healthy male volunteers were studied.
      Mean CSA of the IJV was 1.12 +/- 0.57 cm2 in control, 1.66 +/- 0.67 cm2 in the
      Trendelenburg position (P < 0.0001 vs. control), 0.38 +/- 0.23 cm2 in the reverse
      Trendelenburg position (P < 0.0001 vs. control), and 1.40 +/- 0.64 cm2 during
      passive leg elevation (P < 0.0001 vs. control). Mean CSA of the SCV was 0.92 +/-
      0.23 cm2 in control, 0.98 +/- 0.17 cm2 in the Trendelenburg position, 0.86 +/-
      0.21 cm2 in the reverse Trendelenburg position and 0.93 +/- 0.18 cm2 during
      passive leg elevation. The results indicate that passive leg elevation increases
      the CSA of the IJV, but has little effect on the SCV. The CSA of the IJV appears
      to be influenced more by gravitational factors than the SCV.

PMID- 18326135
TI  - Safety of percutaneous tracheostomy in obese critically ill patients: a
      prospective cohort study.
AB  - Obesity has been described as a relative contraindication for percutaneous
      tracheostomy. The objective of our study was to examine the safety and
      complications of percutaneous tracheostomy in obese patients. We conducted a
      prospective cohort study of all consecutive patients who underwent percutaneous
      tracheostomy at a tertiary medical-surgical intensive care unit between May 2004
      and October 2005. We compared percutaneous tracheostomy in obese patients (body
      mass index > or = 30 kg/m2) to non-obese patients. We documented the occurrence
      of the following complications: aborting the procedure, accidental extubation,
      conversion to surgical tracheostomy, paratracheal placement, the development of
      pneumothorax, major bleeding (requiring blood product transfusion or surgical
      intervention) or death. We also documented hypoxia, minor bleeding (requiring
      pressure dressing or suturing), subcutaneous emphysema and transient hypotension.
      During the study period, 227 percutaneous tracheostomies were performed. There
      were 50 percutaneous tracheostomies in the obese group and 177 in the non-obese
      group. In 45 obese patients, percutaneous tracheostomy was performed without
      bronchoscopic guidance. Major complications were significantly higher in obese
      patients (12% vs. 2%, P = 0.04), while the rate of minor complications was not
      significantly different between the two groups. There were no instances of death
      or pneumothorax, subcutaneous emphysema or need for surgical intervention during
      or in the postoperative period in either group. Our study suggests that
      percutaneous tracheostomy can be performed safely in the majority of obese
      patients.

PMID- 18326136
TI  - A comparison of the effect of total intravenous anaesthesia with propofol and
      remifentanil and inhalational anaesthesia with isoflurane on the release of pro-
      and anti-inflammatory cytokines in patients undergoing open cholecystectomy.
AB  - The aim of the study was to investigate the effects of two anaesthetic techniques
      (total intravenous technique vs. inhalational technique) on changes in pro- and
      anti-inflammatory cytokine levels during open cholecystectomy. Forty ASA PS I-II
      patients undergoing open cholecystectomy were randomly assigned to two groups.
      Group R received total intravenous anaesthesia with propofol and remifentanil and
      group F received balanced inhalational anaesthesia with isoflurane. The plasma
      levels of tumour necrosis factor-alpha (TNF-alpha), interleukin IL-6 and
      interleukin IL-10 were measured during and after surgery. The pro-inflammatory
      cytokine levels (TNF-alpha and IL-6) and the anti-inflammatory cytokine (IL-10)
      showed a significant increase in their concentrations compared with pre-induction
      levels in both groups (P < 0.05). By the end of anaesthesia and surgery, TNF
      alpha and IL-6 were significantly lower in group R than in group F (P < 0.05). At
      the end of anaesthesia and 12 hours postoperatively, IL-10 levels in group R were
      higher than in group F (P < 0.05). These findings suggest that total intravenous
      anaesthesia using propofol and remifentanil suppresses the inflammatory response
      caused by surgery to a greater extent than a balanced inhalation technique using
      isoflurane.

PMID- 18326137
TI  - The use of epidural analgesia in a New Zealand tertiary hospital before and after
      publication of the MASTER study.
AB  - We audited the total number of perioperative epidural techniques performed at
      Christchurch Hospital, New Zealand, for three years, before and after The Lancet
      published the MASTER Anaesthesia Trial in 2002. We also looked specifically at
      the number of epidural anaesthetic and analgesic techniques performed in
      combination with general anaesthesia for colonic surgery over the same period. In
      both cases we found a statistically significant fall in epidural rate in the
      years after the publication (P < 0.001). A subsequent survey of local specialist
      anaesthetists, who have worked throughout this period, revealed the majority
      (75%) were knowingly performing fewer epidural techniques and that the findings
      of the MASTER Anaesthesia Trial had influenced their decisions.

PMID- 18326138
TI  - The pulmonary artery catheter in Australasia: a survey investigating intensive
      care physicians' knowledge and perception of future trends in use.
AB  - A survey was conducted to assess the knowledge and trends of use of the pulmonary
      artery catheter amongst intensive care practitioners in Australasia. A 31-item
      multiple choice questionnaire, identical to one previously trialled in studies in
      the United States and Europe, was distributed to all registered intensive care
      specialists and trainees working in intensive care units in Australasia. Five
      hundred-and-forty-one questionnaires were distributed and 151 (27.9%) were
      returned, with an average mark of 82.7% +/- 9.3% and a range of 53.3 to 100%.
      Total score was significantly associated with years of experience in intensive
      care (P < 0.04), number of pulmonary artery catheters inserted (P < 0.015) and
      whether or not the respondent had passed the Joint Faculty of Intensive Care
      Medicine examination (P < 0.01). Scores were significantly higher amongst
      trainees (P < 0.0001) and physicians who had passed the Joint Faculty of
      Intensive Care Medicine examination (P < 0.0001). Overall, 44.9% of respondents
      indicated their use of the pulmonary artery catheter was decreasing, with 42.6%
      indicating their use was the same over the past five years. Sixty-one percent of
      respondents indicated they either agreed or strongly agreed with the statement
      that the use of echocardiography should supersede the use of the pulmonary artery
      catheter by intensive care specialists in the future. We concluded that in this
      study, knowledge of the pulmonary artery catheter and its use is better in
      Australasia than in previous studies in North America and Europe. The majority of
      respondents in Australasia believe that echocardiography will supersede the use
      of the pulmonary artery catheter in the future.

PMID- 18326139
TI  - Attitudes towards and evaluation of medical emergency teams: a survey of trainees
      in intensive care medicine.
AB  - A survey was conducted to explore the perception of intensive care registrars on
      the impact of activities outside the intensive care unit (ICU), particularly in
      medical emergency teams, on their training and the care of patients. An anonymous
      mail-out survey was sent to 356 trainees registered with the Joint Faculty of
      Intensive Care Medicine, half of whom were determined to be involved in ICU
      duties. No patients were involved and respondents participated voluntarily. The
      main outcome measures were barriers and predictors of satisfaction with ICU
      training. One-hundred-and-thirty-six (38%) trainees responded. Seventy-eight
      percent had participated in a medical emergency team, of whom 99% of respondents
      stated the medical emergency team included an ICU registrar but rarely (3%) an
      ICU consultant. Sixty-six percent of respondents reported that medical emergency
      team involvement had a positive effect on training but 77% reported little or no
      supervision of team duties. While trainees did not believe they spent too much
      time performing medical emergency team duties, the time spent on medical
      emergency teams at night, when ICU staffing levels are at their lowest, was the
      same as during the day. Serious concern was expressed about the negative impact
      of medical emergency team activities on their ability to care for ICU patients
      and the additional stress on ICU medical and nursing staff Overall, ICU trainees
      regarded participation in a medical emergency team as positive on training and on
      patient care in wards, but other results have resource implications for the
      provision of clinical emergency response systems, care of patients in ICUs and
      the training of the future intensive care workforce.

PMID- 18326140
TI  - Immediate management of inadvertent dural puncture during insertion of a labour
      epidural: a survey of Australian obstetric anaesthetists.
AB  - Immediate management of inadvertent dural puncture during insertion of an
      epidural needle during labour is controversial and evidence to guide clinical
      practice is limited. We surveyed Australian obstetric anaesthetists by anonymous
      postal questionnaire. Of the 671 surveys sent, 417 (62%) were returned. Following
      dural puncture, 265 respondents (64%) indicated that they "would usually remove
      the Tuohy needle and resite". The most common reason for this decision was
      concern regarding the safety of intrathecal catheters (ITC) (n = 236, 89%), in
      particular, the risk of misuse (n = 182, 70%). The most frequently reported
      reason for "usually inserting an ITC" was that this reduced the incidence (n =
      120, 84%) and severity (n = 110, 77%) of post dural puncture headache. Increased
      frequency of ITC insertion was reported by respondents who practised more
      frequent sessions of obstetric anaesthesia, had fewer years of experience as a
      consultant anaesthetist and worked in a public hospital. The more widespread use
      of ITCs seems to be limited by safety concerns.

PMID- 18326141
TI  - A survey of the use of unapproved medicines in anaesthesia practice in New
      Zealand.
AB  - The Medicines Act (1981) and its amendments regulate the manufacture, sale and
      supply of medicines, medical devices and related products in New Zealand.
      Medications are approved for supply under the provisions of this Act. Supply and
      administration of unapproved medications is permitted. When this occurs, the
      supplier must report this to the Director-General of Health. Additionally, the
      patient must be informed of the unapproved status of the drug and be advised of
      the forwarding of information related to their health care to a third party. For
      apparently commercial reasons, approval has not been sought for a number of
      formulations of medications commonly used in anaesthesia practice. There has been
      no published literature of the impact of this legislation on the practice of
      anaesthesia in New Zealand. A survey was undertaken to determine how commonly
      anaesthetists administer unapproved drugs, whether the requirements for informed
      consent were met and any perceived impact the status of these medications has on
      patient care. The survey findings indicated that the majority of New Zealand
      anaesthetists practise 'outside the law' with respect to unapproved medicines.
      Seventy-eight percent do not inform patients about the potential use of
      unapproved medications during their anaesthetic, despite 65% administering these
      medications to patients "every few weeks" or even more often.

PMID- 18326142
TI  - Cytomegalovirus colitis in a critically ill patient following elective repair of
      an abdominal aortic aneurysm.
AB  - We describe a case of cytomegalovirus colitis in a critically ill but otherwise
      immunocompetent 61-year-old male. Infection was demonstrated by histology and
      confirmed by plasma polymerase chain reaction and detection of cytomegalovirus
      IgM antibody. The patient was treated with ganciclovir with resolution of the
      cytomegalovirus viraemia. Cytomegalovirus colitis may be an under-recognised
      problem in immunocompetent patients who are critically ill. Quantification of
      plasma cytomegalovirus DNA by polymerase chain reaction is a non-invasive method
      of supporting the diagnosis and can be used to monitor the treatment of
      cytomegalovirus infection in the immunocompetent.

PMID- 18326143
TI  - Insulin infusion via an intraosseous needle in diabetic ketoacidosis.
AB  - We report the successful management of a five-year-old child with severe diabetic
      ketoacidosis with dehydration, who received his initial resuscitative fluids and
      a continuous infusion of insulin via an intraosseous needle. The patient had
      presented to a remote community hospital and intravenous access could not be
      gained. The correction of hyperglycaemia and metabolic acidaemia was achieved at
      a rate comparable to intravenous therapy. No complications were observed.
      Although intraosseous access is well described in paediatric resuscitation
      guidelines, it is not mentioned in International Diabetes Society guidelines for
      the management of diabetic ketoacidosis. Alternatives to intravenous
      administration of insulin delivery recommended in such guidelines, such as the
      subcutaneous or intramuscular routes, may be less appropriate than the
      intraosseous route. This route can also allow resuscitation fluids and other
      drugs to be reliably administered in children with diabetic ketoacidosis and
      severe dehydration where intravenous access can not be attained. We suggest that
      the potential role of intraosseous access, when intravenous access can not be
      obtained, should be considered when management guidelines for paediatric diabetic
      ketoacidosis with dehydration are reviewed.

PMID- 18326144
TI  - Ergometrine administration for post-partum haemorrhage in an undiagnosed pre
      eclamptic.
AB  - We report a case of a parturient who was well antenatally but presented with
      oliguria following delivery. The possibility of post-partum pre-eclampsia was
      obscured by simultaneous post-partum haemorrhage. Ergometrine was given and she
      suffered an eclamptic seizure shortly after. We discuss the diagnostic
      difficulties presented by simultaneous presentation of post-partum pre-eclampsia
      and haemorrhage and the likelihood that ergometrine precipitated eclampsia in a
      patient at risk. While ergometrine is an effective drug for the management of
      uterine atony, its potential role in precipitating eclampsia must be considered.

PMID- 18326145
TI  - Anaesthesia for excision of an intraoral mass in a neonate: use of a laryngeal
      mask during removal of congenital epulis.
AB  - Congenital epulis is a rare intraoral tumour of the newborn arising from gingival
      mucosa, most commonly from the alveolar ridge. It may interfere with normal
      feeding or potentially compromise respiration. We describe the anaesthetic
      management of one such case of a female infant born with a single epulis,
      approximately 3 cm in diameter, protruding from her mouth. The lesion was removed
      one day after delivery, under general anaesthesia using a laryngeal mask airway
      to control the infant's airway. The rationale for this management plan and
      alternatives to this strategy are discussed.

PMID- 18326146
TI  - Continuous interscalene block is preferable to the 'shoulder block' for
      postoperative analgesia following shoulder surgery.

PMID- 18326147
TI  - Another alternative to interscalene block?

PMID- 18326148
TI  - Intra-articular knee joint Botox injection for chronic osteoarthritic pain.

PMID- 18326149
TI  - Paralytic ileus as a complication of iatrogenic hypermagnesaemia without renal
      dysfunction.

PMID- 18326150
TI  - Smoking and otoacoustic emissions.

PMID- 18326151
TI  - The objective and subjective evaluation of low-frequency expansion in wide
      dynamic range compression hearing instruments.
AB  - The effects of low-frequency expansion on the objective and subjective evaluation
      of four channel in-the-ear hearing instruments was investigated. Three expansion
      settings were programmed in each device: expansion off, expansion restricted to
      channel one, and expansion restricted to channels one and two. Objective
      evaluations were conducted in quiet (Connected Speech Test) and in noise (Hearing
      in Noise Test) with speech levels fixed at 40 dB SPL. Subjectively, each
      participant rated expansion satisfaction in quiet and listening to low-level
      speech in a sound-treated room then indicated the expansion condition preferred
      overall. Listeners performed significantly better in quiet and in noise for the
      Off and Channel 1 conditions than the Channels 1 and 2 condition; however,
      performance was similar between the Off and Channel 1 conditions. Expansion
      effects on listener satisfaction ratings depended on the listening environment.
      Overall, listeners preferred expansion in Channel 1 to expansion in Channels 1
      and 2; however, preference was not significantly different between the Channel 1
      and Off conditions. Results indicate restricting expansion to 1000 Hz overcomes
      speech-recognition deficits observed with expansion active across a broader
      spectrum without significantly reducing subjective benefit or preference.

PMID- 18326152
TI  - The value of routine real ear measurement of the gain of digital hearing aids.
AB  - The main aims of this study were: (1) to determine whether routine real ear
      insertion gain (REIG) measurement is necessary in fitting digital hearing aids;
      and (2) to assess the extent to which modifying the frequency-gain response of an
      aid can lead to better matches to the target in cases where the target gain was
      not initially achieved. The target formula was selected as NAL-NL1 in the
      programming software of four types of digital hearing aids. REIG measurements on
      42 ears showed that 64% of cases failed to come within +/-10 dB of the target at
      one or more of the following frequencies: 0.25, 0.5, 0.75, 1, 1.5, 2, and 4 kHz.
      After adjusting the frequency-gain response of the aids, based on the REIG
      results, 83% of cases came within +/-10 dB of the target. The target was met more
      often, both before and after adjustment, for aids with seven gain "handles" than
      for aids with four gain "handles". The results indicate that REIG measurements
      can and should be used to achieve more accurate fittings but that accurate
      adjustments are difficult with some aids.

PMID- 18326153
TI  - Effects of cigarette smoking on distortion product otoacoustic emissions.
AB  - This study measured distortion product otoacoustic emissions (DPOAEs) and DPOAE
      input/output (I/O) curves to assess the effects of smoking on cochlear function.
      Twenty-four healthy adults, 12 smokers and 12 nonsmokers in the 20-30 years age
      range were selected based on self-reported histories of five to eight years of
      smoking or no smoking, respectively. All subjects received tympanometric
      screening to rule out middle ear pathology. Conventional (0.25-8 kHz) and ultra
      high frequency (UHF; 10-20 kHz) audiometry showed normal or age-appropriate
      thresholds across both groups. DPOAE results showed small, but significant,
      decline in DPOAE levels without concomitant changes in noise floors in smokers as
      compared to nonsmokers. I/O detection thresholds were also significantly elevated
      at high frequencies in smokers as compared to their nonsmoking counterparts.
      These findings indicate that smokers are at greater risk for cochlear damage than
      nonsmokers, and that DPOAE amplitudes and I/O detection thresholds may identify
      early changes in cochlear function in smokers.

PMID- 18326154
TI  - Development of an instrument to evaluate audiologic counseling skills.
AB  - This study describes the development of an instrument designed to evaluate
      audiologic counseling skills. In simulated counseling sessions, a trained actor
      portrayed a parent, and ten graduate audiology students role-played counseling
      sessions as audiologists informing the "parent" that her infant has a hearing
      loss. The ten sessions were videotaped, and three raters viewed the taped
      sessions while evaluating counseling skills with a new evaluation tool, the
      Audiologic Counseling Evaluation (ACE). The ACE was found to have excellent
      internal reliability (alpha = .91) and moderate-to-good inter-rater reliability.
      Raters' subjective evaluations of the tool were generally positive, and students'
      evaluations of the simulated counseling experience were overwhelmingly so. This
      instrument can be used by audiology faculty and clinical instructors to help
      students improve their counseling skills before interacting with parents. It can
      also be used in clinical settings for professional development by way of self-
      and peer-evaluation.

PMID- 18326155
TI  - Speech and music quality ratings for linear and nonlinear hearing aid circuitry.
AB  - This study evaluated quality ratings for speech and music stimuli processed using
      peak clipping (PC), compression limiting (CL), and wide-dynamic range compression
      (WDRC) hearing aid circuitry. Eighteen listeners with mild-to-moderate hearing
      loss were binaurally fitted with behind-the-ear (BTE) hearing aids and instructed
      to rate the quality of speech under various conditions in quiet and noise and two
      genres of music. Results for speech revealed a slight preference for WDRC at 80
      dB SPL, and equivalent ratings for the three circuits under all other listening
      conditions. Music ratings revealed a marginally significant preference for WDRC
      and a preference for classical over popular music. For music, judgments on
      pleasantness were the most influential on overall circuit preference.

PMID- 18326156
TI  - Effect of frequency boundary assignment on speech recognition with the Nucleus 24
      ACE speech coding strategy.
AB  - The choice of frequency boundaries for the analysis channels of cochlear implants
      has been shown to impact the speech perception performance of adult recipients
      (Skinner et al, 1995; Fourakis et al, 2004). While technological limitations
      heretofore have limited the clinical feasibility of investigating novel frequency
      assignments, the SPEAR3 research processor affords the opportunity to investigate
      an unlimited number of possibilities. Here, four different assignments are
      evaluated using a variety of speech stimuli. All participants accommodated to
      assignment changes, and no one assignment was significantly preferred. The
      results suggest that better performance can be achieved using a strategy whereby
      (1) there are at least 7-8 electrodes allocated below 1000 Hz, (2) the majority
      of remaining electrodes are allocated between 1100-3000 Hz, and (3) the region
      above 3 kHz is represented by relatively few electrodes (i.e., 1-3). The results
      suggest that such frequency assignment flexibility should be made clinically
      available.

PMID- 18326157
TI  - The words-in-noise (WIN) test with multitalker babble and speech-spectrum noise
      maskers.

PMID- 18326158
TI  - First-line therapies for lowering triglyceride levels.

PMID- 18326159
TI  - Managing hypertriglyceridemia with diet modifications.

PMID- 18326160
TI  - Endocarditis prophylaxis: an evolution of change.

PMID- 18326161
TI  - A long recovery.

PMID- 18326162
TI  - Are long-acting insulin analogues better than isophane insulin?

PMID- 18326163
TI  - Cancer genetic risk assessment for individuals at risk of familial breast cancer.

PMID- 18326164
TI  - Chronic shoulder pain: part I. Evaluation and diagnosis.
AB  - Shoulder pain is defined as chronic when it has been present for longer than six
      months. Common conditions that can result in chronic shoulder pain include
      rotator cuff disorders, adhesive capsulitis, shoulder instability, and shoulder
      arthritis. Rotator cuff disorders include tendinopathy, partial tears, and
      complete tears. A clinical decision rule that is helpful in the diagnosis of
      rotator cuff tears includes pain with overhead activity, weakness on empty can
      and external rotation tests, and a positive impingement sign. Adhesive capsulitis
      can be associated with diabetes and thyroid disorders. Clinical presentation
      includes diffuse shoulder pain with restricted passive range of motion on
      examination. Acromioclavicular osteoarthritis presents with superior shoulder
      pain, acromioclavicular joint tenderness, and a painful cross-body adduction
      test. In patients who are older than 50 years, glenohumeral osteoarthritis
      usually presents as gradual pain and loss of motion. In patients younger than 40
      years, glenohumeral instability generally presents with a history of dislocation
      or subluxation events. Positive apprehension and relocation are consistent with
      the diagnosis. Imaging studies, indicated when diagnosis remains unclear or
      management would be altered, include plain radiographs, magnetic resonance
      imaging, ultrasonography, and computed tomography scans. Plain radiographs may
      help diagnose massive rotator cuff tears, shoulder instability, and shoulder
      arthritis. Magnetic resonance imaging and ultrasonography are preferred for
      rotator cuff disorders. For shoulder instability, magnetic resonance imaging
      arthrogram is preferred over magnetic resonance imaging.

PMID- 18326166
TI  - Testicular cancer: what you should know.

PMID- 18326165
TI  - Diagnosis and treatment of testicular cancer.
AB  - Testicular cancer is the most common malignancy in men 20 to 35 years of age and
      has an annual incidence of four per 100,000. If diagnosed early, the cure rate is
      nearly 99 percent. Risk factors for testicular cancer include cryptorchidism
      (i.e., undescended testicles), family history, infertility, tobacco use, and
      white race. Routine self-examination and physician screening have not been shown
      to improve outcomes, and the U.S. Preventive Services Task Force and American
      Cancer Society do not recommend them in asymptomatic men. Patients presenting
      with a painless testicular mass, scrotal heaviness, a dull ache, or acute pain
      should receive a thorough examination. Testicular masses should be examined with
      scrotal ultrasonography. If ultrasonography shows an intratesticular mass, the
      patient should be referred to a urologist for definitive diagnosis, orchiectomy,
      and further evaluation with abdominal computed tomography and chest radiography.
      The family physician's role after diagnosis of testicular cancer includes
      encouraging the patient to bank sperm because of possible infertility and
      evaluating for recurrence and future complications, especially cardiovascular
      disease.

PMID- 18326167
TI  - Reducing tobacco use in adolescents.
AB  - After steadily decreasing since the late 1990s, adolescent smoking rates have
      stabilized at levels well above national goals. Experts recommend screening for
      tobacco use and exposure at every patient visit, although evidence of improved
      outcomes in adolescents is lacking. Counseling should be provided using the 5-A
      method (ask, advise, assess, assist, and arrange). All smokers should be offered
      smoking cessation assistance, including counseling, nicotine replacement therapy,
      bupropion therapy, or combination therapy. Pharmacotherapy of any kind doubles
      the likelihood of successful smoking cessation in adults; however, nicotine
      replacement therapy is the only pharmacologic intervention that has been
      extensively studied in children. Community interventions such as smoking bans and
      educational programs have been effective at reducing smoking rates in children
      and adolescents. Antismoking advertising and tobacco sales taxes also help deter
      new smokers and motivate current smokers to attempt to quit.

PMID- 18326168
TI  - Tobacco use: what teenagers should know.

PMID- 18326169
TI  - Chronic shoulder pain: part II. Treatment.
AB  - Chronic shoulder pain is a common problem in the primary care physician's office.
      Effective treatment depends on an accurate diagnosis of the more common
      etiologies: rotator cuff disorders, adhesive capsulitis, acromioclavicular
      osteoarthritis, glenohumeral osteoarthritis, and instability. Activity
      modification and analgesic medications comprise the initial treatment in most
      cases. If this does not lead to improvement, or if the initial presentation is of
      sufficient severity, a trial of physical therapy that focuses on the specific
      diagnosis is indicated. Combined steroid and local anesthetic injections can be
      used alone or as an adjuvant to the physical therapy. The site of the injection
      (subacromial, acromioclavicular joint, or intra-articular) depends on the
      diagnosis. Injections into the glenohumeral joint should be done under
      fluoroscopic guidance. Symptoms that persist or worsen after six to 12 weeks of
      directed treatment should be referred to an orthopedic specialist.

PMID- 18326170
TI  - A purpuric rash and mononeuritis multiplex.

PMID- 18326171
TI  - Initial counseling of children with eating disorders and their families.

PMID- 18326172
TI  - Transfer of Escherichia coli O157:H7 to romaine lettuce due to contact water from
      melting ice.
AB  - Ice can be used to chill romaine lettuce and maintain relative humidity during
      transportation. Escherichia coli O157:H7 may contaminate water used for ice. The
      objective of this study was to determine the potential for E. coli O157:H7
      contamination of romaine lettuce from either ice contaminated with the pathogen
      or by transfer from lettuce surfaces via melting ice. In experiment 1, lettuce
      was spot inoculated with E. coli O157:H7 and chilled with ice prepared from
      uncontaminated tap water. In experiment 2, water inoculated with this pathogen
      was frozen and used to ice lettuce. Three heads of lettuce were stacked in each
      container and stored at 4 or 20 degrees C. After the ice melted, E. coli O157:H7
      attachment to and recovery from the lettuce leaves were determined. For
      experiment 1, the population of E. coli O157:H7 attached to inoculated sites
      averaged 3.8 and 5.5 CFU/cm2 at 4 and 20 degrees C, respectively. Most of the
      uninoculated sites became contaminated with the pathogen due to ice melt. For
      experiment 2, 3.5 to 3.8 log CFU E. coli O157:H7 per cm2 was attached to the top
      leaf on the first head. After rinsing with chlorinated water (200 microg/ml), E.
      coli O157:H7 remained on the surface of the top head (1.8 to 2.0 log CFU/cm2).
      There was no difference in numbers of E. coli O157:H7 recovered from each
      sampling site at 4 and 20 degrees C. Results show that E. coli O157:H7 can be
      transferred onto other produce layers in shipping containers from melted ice made
      of contaminated water and from contaminated to uncontaminated leaf surfaces.

PMID- 18326173
TI  - Risk assessment for Escherichia coli O157:H7 in marketed unpasteurized milk in
      selected East African countries.
AB  - We carried out a study to assess the risk associated with the presence of Shiga
      toxigenic Escherichia coli (STEC) in informally marketed unpasteurized milk in
      urban East Africa. Data for the risk models were obtained from on-going and
      recently completed studies in Kenya and Uganda. Inputs for the model were
      complemented with data from published literature in similar populations. A fault
      tree scenario pathway and modular process risk model approach were used for
      exposure assessment. Hazard characterization was based on a socioeconomic study
      with dose-responses derived from the literature. We used a probabilistic approach
      with Monte Carlo simulation and inputs from farm and household surveys. The
      qualitative analysis suggested a low to moderate risk of infection from consuming
      milk and that the widespread consumer practice of boiling milk before consumption
      was an important risk mitigator. Quantitative analysis revealed that two to three
      symptomatic STEC infections could be expected for every 10,000 unpasteurized milk
      portions consumed, with a possible range of 0 to 22 symptomatic cases.
      Sensitivity analyses to assess the uncertainty and variability associated with
      the model revealed that the factor with the greatest influence on disease
      incidence was the prevalence of STEC in dairy cattle. Risk assessment is a
      potentially useful method for managing food safety in informal markets.

PMID- 18326174
TI  - Sources and spread of thermophilic Campylobacter spp. during partial depopulation
      of broiler chicken flocks.
AB  - The practice of partial depopulation or thinning (early removal of a portion of
      birds from a commercial broiler flock) is a reported risk factor for
      Campylobacter colonization of residual birds because of the difficulty in
      maintaining biosecurity during the thinning process. The effect of this practice
      was studied in detail for 51 target flocks, each at a different growing farm
      belonging to one of seven major poultry companies throughout the United Kingdom.
      On 21 of these farms, the target flock was already colonized by Campylobacter,
      and at slaughter all cecal samples examined were positive, with a mean of 8 log
      CFU/g. An additional 27 flocks became positive within 2 to 6 days of the start of
      thinning and had similarly high levels of cecal carriage at slaughter. Just
      before the thinning process, Campylobacter was isolated frequently from the farm
      driveways, transport vehicles, equipment, and personnel. Strains from seven farms
      on which flocks became colonized after thinning were examined by pulsed-field gel
      electrophoresis typing. An association was found between strains occurring at
      specific sampling sites and those isolated subsequently from the thinned flocks.
      The results indicated that particular strains had spread from one farm to another
      when the farms were jointly owned by the same company and employed the same bird
      catching teams and/or vehicles. These results highlight the need for better
      hygiene control in relation to catching equipment and personnel and more
      effective cleaning and disinfection of vehicles and bird-transport crates.

PMID- 18326175
TI  - Temperature and nutrient effects on Campylobacter jejuni attachment on
      multispecies biofilms on stainless steel.
AB  - Campylobacterjejuni is a thermophilic microaerophilic pathogen that is commonly
      found in the intestinal tract of chickens. In this study, attachment of C. jejuni
      1221gfp in biofilms on stainless steel was assessed at various temperatures and
      with reduced nutrients. Bacteria collected from a saline rinse of processed
      broiler chicken carcasses were used to form initial biofilms. The whole carcass
      rinse (WCR) biofilms were formed by incubation of the bacteria for 16 h at 13,
      20, 37, and 42 degrees C on stainless steel coupons in tryptic soy broth (TSB).
      The resulting biofilms were stained with Hoechst 33258 stain and visualized by
      epifluorescence microscopy. WCR biofilms formed at 13 degrees C yielded the
      highest surface area coverage (47.6%), and the lowest coverage (2.1%) was
      attained at 42 degrees C. C. jejuni transformed to produce green fluorescent
      protein (gfp) was allowed to attach to the preexisting biofilms (from WCR
      incubated for 16 h) at each of the four temperatures, and attached cells were
      enumerated by visualization with an epifluorescence microscope. Attachment of C.
      jejuni 1221gfp did not significantly differ (P > 0.05) among the four
      temperatures. C. jejuni 1221gfp was cultured only from coupons with biofilms
      formed at 13 and 20 degrees C. For nutrient limitation experiments, WCR biofilms
      were allowed to grow in 10- and 50-fold diluted TSB at 20 and 37 degrees C for 48
      h. The WCR biofilm surface area coverage (approximately 2%) was greater at 37
      degrees C than at 20 degrees C for both TSB concentrations. C. jejuni 1221gfp was
      incubated with the WCR biofilm for 48 h at 20 and 37 degrees C, and attached
      cells were enumerated. Attachment was significantly higher (P < 0.05) only for
      the treatments with 1:10 TSB at 20 degrees C and 1:50 TSB at 37 degrees C. Under
      reduced-nutrient conditions, C. jejuni 1221gfp was cultured only from biofilms
      formed at 20 degrees C. Under the conditions tested, the attachment of C. jejuni
      1221gfp on stainless steel and biofilms was affected by a combination of
      temperature and nutrient availability, but C. jejuni culturability was affected
      solely by temperature.

PMID- 18326176
TI  - Modeling the effect of prior sublethal thermal history on the thermal
      inactivation rate of Salmonella in ground turkey.
AB  - Traditional models for predicting the thermal inactivation rate of bacteria are
      state dependent, considering only the current state of the product. In this
      study, the potential for previous sublethal thermal history to increase the
      thermotolerance of Salmonella in ground turkey was determined, a path-dependent
      model for thermal inactivation was developed, and the path-dependent predictions
      were tested against independent data. Weibull-Arrhenius parameters for Salmonella
      inactivation in ground turkey thigh were determined via isothermal tests at 55,
      58, 61, and 63 degrees C. Two sets of nonisothermal heating tests also were
      conducted. The first included five linear heating rates (0.4, 0.9, 1.7, 3.5, and
      7.0 K/min) and three holding temperatures (55, 58, and 61 degrees C); the second
      also included sublethal holding periods at 40, 45, and 50 degrees C. When the
      standard Weibull-Arrhenius model was applied to the nonisothermal validation data
      sets, the root mean squared error of prediction was 2.5 log CFU/g, with fail
      dangerous residuals as large as 4.7 log CFU/g when applied to the complete
      nonisothermal data set. However, by using a modified path-dependent model for
      inactivation, the prediction errors for independent data were reduced by 56%.
      Under actual thermal processing conditions, use of the path-dependant model would
      reduce error in thermal lethality predictions for slowly cooked products.

PMID- 18326177
TI  - Heterogeneous photocatalytic disinfection of wash waters from the fresh-cut
      vegetable industry.
AB  - The effectiveness of photocatalytic disinfection for control of natural and
      potentially pathogenic microflora in wash waters used for fresh-cut vegetables
      was evaluated. Wash waters for lettuce, escarole, chicory, carrot, onion, and
      spinach from a fresh-cut vegetable processing plant were treated with a titanium
      dioxide (TiO2) photocatalytic system. The vegetable wash waters were impelled out
      with a pump at a flow rate of 1,000 liters/h and conducted through a stainless
      steel circuit to the filtration system to reach the TiO2 photocatalyst fiber,
      which was illuminated with a 40-W UV-C lamp. The microbial and physicochemical
      qualities of the wash water were analyzed. Heterogeneous photocatalysis was an
      effective disinfection method, reducing counts of bacteria, molds, and yeasts.
      Most of the treated wash waters had total bacteria reductions of 4.1 +/- 1.3 to
      4.8 +/- 0.4 log CFU/ml after 10 min of treatment when compared with untreated
      water. Higher decontamination efficacy was observed in carrot wash water (6.2 +/-
      0.1-log reductions), where turbidity and organic matter were lower than those in
      the wash waters for other vegetables. The tested heterogeneous photocatalytic
      system also was effective for reducing water turbidity, although chemical oxygen
      demand was unaffected after the treatments. The efficacy of the photocatalytic
      system for reducing microbial load depended on the physicochemical
      characteristics of the wash water, which depended on the vegetable being washed.
      The conclusions derived from this study illustrate that implementation of a
      heterogeneous photocatalytic system in the fresh-cut vegetable washing processes
      could allow the reuse of wash water.

PMID- 18326178
TI  - Spoilage and safety characteristics of ground beef packaged in traditional and
      modified atmosphere packages.
AB  - Two separate studies, one with pathogen-inoculated product and one with
      noninoculated product, were conducted to determine the safety and spoilage
      characteristics of modified atmosphere packaging (MAP) and traditional packaging
      of ground beef patties. Ground beef patties were allotted to five packaging
      treatments (i) control (foam tray with film overwrap; traditional), (ii) high
      oxygen MAP (80% 02, 20% CO2), (iii) high-oxygen MAP with added rosemary extract,
      (iv) low-oxygen carbon monoxide MAP (0.4% CO, 30% CO2, 69.6% N2), and (v) low
      oxygen carbon monoxide MAP with added rosemary extract. Beef patties were
      evaluated for changes over time (0, 1, 3, 5, 7, 14, and 21 days) during lighted
      display. Results indicated low-oxygen carbon monoxide gas flush had a stabilizing
      effect on meat color after the formation of carboxymyoglobin and was effective
      for preventing the development of surface discoloration. Consumers indicated that
      beef patties packaged in atmospheres containing carbon monoxide were more likely
      to smell fresh at 7, 14, and 21 days of display, but the majority would probably
      not consume these products after 14 days of display because of their odor. MAP
      suppressed the growth of psychrophilic aerobic bacteria when compared with
      control packages. Generally, control packages had significantly higher total
      aerobic bacteria and Lactobacillus counts than did modified atmosphere packages.
      In the inoculated ground beef (approximately 10(5) CFU/g) in MAP, Escherichia
      coli O157 populations ranged from 4.51 to 4.73 log CFU/g with no differences
      among the various packages, but the total E. coli O157:H7 in the ground beef in
      the control packages was significantly higher at 5.61 log CFU/g after 21 days of
      storage. On days 14 and 21, the total Salmonella in the ground beef in control
      packages was at 5.29 and 5.27 log CFU/g, respectively, which was significantly
      higher than counts in the modified atmosphere packages (3.99 to 4.31 log CFU/g on
      day 14 and 3.76 to 4.02 log CFU/g on day 21). Data from these studies indicate
      that MAP suppresses pathogen growth compared with controls and that spoilage
      characteristics developed in MAP packages.

PMID- 18326179
TI  - Cold atmospheric plasma decontamination of the pericarps of fruit.
AB  - This investigation describes the inactivation by cold atmospheric plasmas of one
      pathogenic and three spoilage organisms on the pericarps of mangoes and melons.
      The operating voltage necessary for efficient microbial decontamination of fruit
      pericarps was first established using Escherichia coli at a concentration of
      10(7) CFU/cm2 on the surface of mango. It was found that, when the plasma was
      sustained slightly above its breakdown voltage of 12 kV (peak to peak), no
      inactivation was detected when cells were plated onto tryptone soya extract agar
      (TSA). However, when plated onto eosin methylene blue agar, sublethal injury
      corresponding to approximately 1 log reduction was achieved, whereas on TSA
      supplemented with 4% NaCl a greater reduction of 1.5 log was revealed. When the
      voltage was increased by 33% to 16 kV, a reduction in cell counts of 3 log was
      achieved on all three plating media. Further investigations at these new
      operating conditions were conducted using a range of spoilage microorganisms
      (Saccharomyces cerevisae, Pantoea agglomerans, and Gluconacetobacter
      liquefaciens) all at a surface concentration of 106 CFU/cm2 on the pericarps of
      mango and melon. P. agglomerans and G. liquefaciens were reduced below the
      detection limit (corresponding to 3 log) after only 2.5 s on both fruits, whereas
      E. coli required 5 s to reach the same level of inactivation. S. cerevisae was
      the most resistant organism studied and was reduced in numbers below the
      detection limit after 10 s on mango and 30 s on melon. The optical emission
      spectra generated by the cold atmospheric plasma at both high and low operating
      voltages were compared in order to identify putative lethal species. It was shown
      that an increase in the applied voltage led to more efficient production of
      reactive plasma species, particularly oxygen atoms, and the production of oxygen
      atoms was related to the level of bacterial inactivation achieved. Production of
      atomic oxygen could be used as an indicator of inactivation efficiency for
      scaling up cold plasma systems for whole fruit.

PMID- 18326180
TI  - Microbiological safety of sandwiches from hospitals and other health care
      establishments in the United Kingdom with a focus on Listeria monocytogenes and
      other Listeria species.
AB  - In the United Kingdom between 1999 and 2004, there were four outbreaks of
      Listeria monocytogenes infection associated with sandwiches purchased from or
      provided in hospitals. Elderly or immunocompromised individuals and pregnant
      women are particularly vulnerable to infection; therefore, the focus of this
      study was on sandwiches served in health care establishments. Of 3,249 sandwich
      samples collected between April 2005 and March 2006, 3.3% were of unsatisfactory
      microbiological quality because of high levels of Enterobacteriaceae (2.0%; > or
      = 10(4) CFU/g for sandwiches not containing salad), Escherichia coli (0.8%; > or
      = 10(2) CFU/g), Staphylococcus aureus (0.6%; > or = 10(2) CFU/g), and/or Listeria
      spp. (0.1%; two samples with L. welshimeri at 1.8 x 10(2) and 7.4 x 10(3) CFU/g
      and one sample with L. seeligeri at 1.8 x 10(3) CFU/g). Overall, 7.6% of
      sandwiches were contaminated with Listeria spp. L. monocytogenes was detected in
      2.7% (88) of samples: 87 samples at < 10 CFU/g and 1 sample at 20 CFU/g. More
      frequent contamination with Listeria spp. and L. monocytogenes was found in
      sandwiches collected from hospital cafeterias, shops, or wards and in sandwiches
      stored and/or displayed at temperatures higher than 8 degrees C. The presence of
      Listeria spp. and L. monocytogenes also was associated with sandwiches that (i)
      were supplied from outside the establishment, (ii) were prepacked, (iii) had a
      main sandwich filling of poultry meat, or (iv) contained salad ingredients, soft
      cheese, and/or mayonnaise. Control of L. monocytogenes in sandwich manufacturing
      and within health care establishments is essential to minimize the potential for
      consumption of this bacterium at levels hazardous to health. The findings from
      this study support the proposal that manufacturers supplying sandwiches to health
      care establishments should follow the British Sandwich Association recommended
      guidelines of complete absence of L. monocytogenes in sandwiches at the point of
      production.

PMID- 18326181
TI  - Antimicrobial activity of lactoferrin against foodborne pathogenic bacteria
      incorporated into edible chitosan film.
AB  - The objectives of this research were to develop and characterize edible chitosan
      film containing lactoferrin as a natural antimicrobial agent, and to investigate
      the combination effects of lactoferrin with lysozyme in chitosan film against the
      growth of Escherichia coli O157:H7 and Listeria monocytogenes. Chitosan films
      containing lactoferrin, lysozyme, or nisin were fabricated, and the antimicrobial
      concentrations were 0.5, 1, or 2 mg in a circular disc of chitosan film. Three
      concentrations of lactoferrin or EDTA (0.28, 0.56, or 1.12 mg per disc) were also
      incorporated into the chitosan film containing lysozyme to investigate the
      combination effects of lactoferrin. The water barrier properties of the chitosan
      films containing lactoferrin were characterized. The antimicrobial activities
      against E. coli O157:H7 and L. monocytogenes were determined using the agar
      diffusion assay and cell count assay. The chitosan films containing lactoferrin
      less than 1 mg per disc did not alter the water vapor permeability of the
      chitosan film. Although the film containing lysozyme exhibited significant
      antimicrobial activity, the incorporation of lactoferrin alone into chitosan film
      did not exhibit significant antimicrobial activity against both E. coli O157:H7
      and L. monocytogenes. However, the combination of lactoferrin with lysozyme
      containing chitosan film significantly decreased the growth of E. coli O157:H7,
      exhibiting a comparable effect to that of the combination of EDTA with lysozyme
      (P < 0.05). Furthermore, the combination of lactoferrin with lysozyme in chitosan
      film exhibited greater reduction in the growth of L. monocytogenes than did the
      combination EDTA with lysozyme, resulting in an approximate 3-log reduction.

PMID- 18326182
TI  - Growth inhibitory effects of kimchi (Korean traditional fermented vegetable
      product) against Bacillus cereus, Listeria monocytogenes, and Staphylococcus
      aureus.
AB  - Kimchi is a unique Korean traditional vegetable product that is fermented by
      lactic acid bacteria (LAB) and is mainly consumed as a side dish with boiled
      rice. Its main ingredients are brined Chinese cabbage, red pepper powder, and
      fermented fish sauce, and these are combined with many spices such as garlic,
      green onion, ginger, and some seaweed. The relationship between the concentration
      of LAB or the pH and the growth of three gram-positive foodborne pathogens
      (Bacillus cereus, Listeria monocytogenes, and Staphylococcus aureus) was
      evaluated. Heat treatment (HT; 85 degrees C for 15 min) or neutralization
      treatment (NT; pH 7.0) was conducted on day 0 (0-D group) and day 3 (3-D group)
      of incubation. The pH in the control group and the NT group dropped sharply to
      4.12 to 4.30 after 2 days of incubation and slightly decreased thereafter,
      whereas the pH in the control group and HT group stayed at 7.0 during incubation.
      LAB were not detected in the HT kimchi during incubation. B. cereus in the NT-0
      D, NT-3-D, and HT-3-D groups was reduced by 1.5 to 3.1 log CFU/ml but increased
      slightly in the HT-0-D group. L. monocytogenes in HT-3-D and NT-3-D groups
      disappeared after 5 days of incubation, and S. aureus in the NT-0-D group
      disappeared after 4 days. These findings indicate that growth of all the
      foodborne pathogens was inhibited by NT-0-D, HT-3-D, and NT-3-D, but B. cereus
      was not inhibited by HT-0-D. Thus, growth of LAB in kimchi is an important factor
      in the control of foodborne pathogens.

PMID- 18326183
TI  - Inactivation kinetics of avirulent Bacillus anthracis spores in milk with a
      combination of heat and hydrogen peroxide.
AB  - The combined effect of heat and hydrogen peroxide (HP) on the inactivation of
      avirulent Bacillus anthracis spores (Sterne strain 7702; strain ANR-1, an
      avirulent Ames derivative lacking the pXO2 plasmid; and strain 9131, a plasmid
      less Sterne strain) was evaluated in milk. The study temperature ranged from 90
      to 95 degrees C, and the concentration of added HP varied from 0.05 to 0.5%.
      Decimal reduction times (D-values) were determined using a sealed capillary tube
      technique. The mean D- and z-values of hydrated freeze-dried spores of all three
      strains in milk ranged from 550 s at 90 degrees C to 180 s at 94 degrees C and
      from 8.6 to 9.0 degrees C, respectively. When 0.05% HP was added to the milk, the
      D-values were decreased at least threefold, and at 0.5% HP the D-values ranged
      from 1 to 10 s. At 90 degrees C, all three strains had similar D-values when
      0.05% HP was added. Increasing the concentration of HP to 0.5% had a greater
      reducing effect on the D-value for strain 7702 than on the values for strains ANR
      1 and 9131. The rate of inactivation of each strain followed first-order reaction
      kinetics at each temperature-peroxide combination. Equations in the form of D =
      Constant x (HP concentration)n had R2 values greater than 0.97 for strains ANR-1
      and 7702 and of at least 0.7 for strain 9131. This study suggests that a
      combination of high temperature (from 90 to 95 degrees C) and HP could be used
      for inactivation of B. anthracis spores in the event of deliberate contamination
      of milk such that the contaminated milk could be disposed of safely.

PMID- 18326184
TI  - Phenotypic and molecular assessment of antimicrobial resistance in Lactobacillus
      paracasei strains of food origin.
AB  - Antimicrobial resistance data in food-associated lactic acid bacteria (LAB) such
      as lactobacilli are mostly based on nonstandardized methodologies and/or have
      been obtained for only a limited number of strains. This susceptibility study
      included a diverse collection of 115 isolates mainly of food origin originally
      identified as Lactobacillus paracasei or Lactobacillus casei. Upon
      reidentification and removal of potential replicate isolates using repetitive DNA
      element PCR fingerprinting, 65 genotypically unique L. paracasei strains and the
      L. casei type strain were selected for broth microdilution and Etest assays using
      the LAB susceptibility test medium. In both methodologies, strains appeared
      uniformly susceptible to ampicillin and clindamycin but exhibited natural
      resistance to streptomycin and gentamicin. Three L. paracasei strains from cheese
      displayed acquired resistance to tetracycline (MIC > or = 32 microg/ml) and/or to
      erythromycin (MIC >16 microg/ml), which was linked to the presence of a tet(M) or
      tet(W) gene and/or an erm(B) gene, respectively. Partial sequencing revealed that
      the tet(M) genes found in two of these strains belonged to two tet(M) sequence
      homology groups previously found in enterococci. Collectively, phenotypic and
      genotypic data allowed us to propose tentative epidemiological cutoffs for L.
      paracasei and L. casei for differentiating susceptible strains from those strains
      harboring one or more acquired resistance factors.

PMID- 18326185
TI  - Effect of high hydrostatic pressure processing on freely suspended and bivalve
      associated T7 bacteriophage.
AB  - The effectiveness of hydrostatic pressure processing (HPP) for inactivating
      viruses has been evaluated in only a limited number of studies, and most of the
      work has been performed with viruses freely suspended in distilled water. In this
      work, HPP inactivation of freely suspended and shellfish-associated bacteriophage
      T7 was studied. T7 was selected in hopes that it could serve as a model for
      animal virus behavior. Clams (Mercenaria mercenaria) and oysters (Crassostrea
      virginica) were homogeneously blended separately and inoculated with
      bacteriophage T7. The inoculated bivalve meat and the freely suspended virus
      samples were subjected to HPP under the following conditions: 2, 4, and 6 min at
      241.3, 275.8, and 344.7 MPa pressure and temperatures of 29.4 to 35, 37.8 to
      43.3, and 46.1 to 51.7 degrees C. Reductions of 7.8 log PFU (100% inactivation)
      were achieved for freely suspended T7 at 344.7 MPa for 2 min at 37.8 to 43.3
      degrees C. At 46.1 to 51.7 degrees C, T7 associated with either clams or oysters
      was inactivated at nearly 100% (>4 log PFU) at all pressure levels and durations
      tested. These results indicate that T7 is readily inactivated by HPP under the
      proper conditions, may be made more susceptible to HPP by mixing with shellfish
      meat, and may serve as a viable model for the response of several animal viruses
      to HPP.

PMID- 18326186
TI  - Acaricidal activity of Thymus vulgaris oil and its main components against
      Tyrophagus putrescentiae, a stored food mite.
AB  - The acaricidal activities of compounds derived from Thymus vulgaris (thyme) oil
      against Tyrophagus putrescentiae were assessed using an impregnated fabric disk
      bioassay, and were compared with those of the synthetic acaricides, benzyl
      benzoate and N,N-diethyl-m-toluamide. The observed responses differed according
      to dosage and chemical components. The 50% lethal dose (LD50) value of the T.
      vulgaris oil against T. putrescentiae was 10.2 microg/cm2. Biologically active
      constituents derived from T. vulgaris oil were purified by using silica gel
      chromatography and high-performance liquid chromatography. The structures of
      acaricidal components were analyzed by gas chromatography-mass spectrometry, 1H
      nuclear magnetic resonance (NMR), 13C NMR, 1H-13C COSY-NMR, and DEPT-NMR spectra,
      and were subsequently identified as carvacrol and thymol. Carvacrol was the most
      toxic compound with LD50 values (4.5 microg/cm2) significantly different from
      thymol (11.1 microg/cm2), benzyl benzoate (11.3 microg/cm2), and N,N-diethyl-m
      toluamide (13.9 microg/cm2). Linalool was as toxic as was N,N-diethyl-m
      toluamide. The lower LD50 of carvacrol indicates that it may be the major
      contributor of the toxicity of T. vulagaris oil against the stored food mite,
      although it only constitutes 14.2% of the oil. From this point of view, carvacrol
      and thymol can be very useful as potential control agents against stored food
      mite.

PMID- 18326187
TI  - Juice-associated outbreaks of human illness in the United States, 1995 through
      2005.
AB  - Outbreaks of illness associated with consumption of fruit juice have been a
      growing public health problem since the early 1990s. In response to epidemiologic
      investigations of outbreaks in which juice was implicated, the U.S. Food and Drug
      Administration implemented process control measures to regulate the production of
      fruit juice. The final juice regulation, which became effective in 2002, 2003,
      and 2004, depending on the size of the business, requires that juice operations
      comply with a hazard analysis critical control point (HACCP) plan. The Centers
      for Disease Control and Prevention (CDC) receives reports of food-associated
      outbreaks of illness. We reviewed fruit juice-associated outbreaks of illness
      reported to the CDC's Foodborne Outbreak Reporting System. From 1995 through
      2005, 21 juice-associated outbreaks were reported to CDC; 10 implicated apple
      juice or cider, 8 were linked to orange juice, and 3 involved other types of
      fruit juice. These outbreaks caused 1,366 illnesses, with a median of 21 cases
      per outbreak (range, 2 to 398 cases). Among the 13 outbreaks of known etiology, 5
      were caused by Salmonella, 5 by Escherichia coli O157:H7, 2 by Cryptosporidium,
      and one by Shiga toxin-producing E. coli O111 and Cryptosporidium. Fewer juice
      associated outbreaks have been reported since the juice HACCP regulation was
      implemented. Some juice operations that are exempt from processing requirements
      or do not comply with the regulation continue to be implicated in outbreaks of
      illness.

PMID- 18326188
TI  - FoodNet survey of food use and practices in long-term care facilities.
AB  - Foodborne illness is an important problem among the elderly. One risk factor for
      foodborne illness and diarrhea-associated mortality among the elderly is
      residence in a long-term care facility (LTCF); thus, these facilities must
      implement measures to ensure safe food. To assess safe food practices, knowledge,
      and policies, we used a mailed, self-administered questionnaire to survey food
      service directors at LTCFs that were certified to receive Medicare or Medicaid at
      eight Foodborne Diseases Active Surveillance Network (FoodNet) sites. Surveys
      were distributed to 1,630 LTCFs; 55% (865 of 1,568) of eligible facilities
      returned a completed questionnaire. Only three LTCFs completely followed national
      recommendations for prevention of Listeria monocytogenes contamination. Nine
      percent of LTCFs reported serving soft cheeses made from unpasteurized milk. Most
      LTCFs reported routinely serving ready-to-eat deli meats; however, few reported
      always heating deli meats until steaming hot before serving (only 19% of the
      LTCFs that served roast beef, 13% of those that served turkey, and 11% of those
      that served ham). Most LTCFs (92%) used pasteurized liquid egg products, but only
      36% used pasteurized whole shell eggs. Regular whole shell eggs were used by 62%
      of facilities. Few LTCFs used irradiated ground beef (7%) or irradiated poultry
      products (6%). The results of this survey allowed us to identify several
      opportunities for prevention of foodborne illnesses in LTCFs. Some safety
      measures, such as the use of pasteurized and irradiated foods, were
      underutilized, and many facilities were not adhering to national recommendations
      on the avoidance of certain foods considered high risk for elderly persons.
      Enhanced educational efforts focusing on food safety practices and aimed at LTCFs
      are needed.

PMID- 18326189
TI  - Effect of incubation temperature on aerobic plate counts of beef and sheep
      carcasses.
AB  - Australian regulations for microbiological testing of carcasses specify a number
      of incubation temperatures and media for meat processed at both domestic and
      export establishments. Accordingly, the effect of incubation temperature and
      media on aerobic plate counts of samples from beef and sheep carcasses was
      investigated. For both species, aerobic plate counts on Petrifilm incubated at 35
      degrees C were significantly lower than those counts on Petrifilm and pour plates
      incubated at 25 and 30 degrees C, reflecting the inability of many psychrotrophs
      to grow at 35 degrees C. When samples were taken from carcasses that had been
      stored in abattoir chillers for periods between 16 h and 5 days, difference
      between counts at 35 degrees C versus those incubated at 25 and 30 degrees C
      became greater as the period of refrigerated storage increased. For export beef
      carcasses, the effect of this difference is minimal, since the vast majority of
      counts incubated at 35 degrees C are done on carcasses that have been chilled for
      less than 24 h and will not have a large proportion of psychrotrophs.

PMID- 18326190
TI  - Enumeration of Enterobacteriaceae in various foods with a new automated most
      probable-number method compared with petrifilm and international organization for
      standardization procedures.
AB  - An automated most-probable-number (MPN) system (TEMPO, bioMerieux, Marcy
      l'Etoile, France) for enumeration of Enterobacteriaceae (EB) was compared with
      methods involving violet red bile glucose agar (VRBG) (International Organization
      for Standardization [ISO] method 21528-2) (ISO-VRBG) and Petrifilm (PF-EB). The
      MPN partitioning (three different volumes with 16 replicates of each) is done
      automatically in a disposable card. Bacterial growth is indicated by acid
      production from sugars, lowering the pH of the medium, and quenching the
      fluorescence of 4-methylumbelliferone. After incubation, the number of
      nonfluorescent wells is read in a separate device, and the MPN is calculated
      automatically. A total of 411 naturally contaminated foods were tested, and 190
      were in the detection range for all methods. For these results, the mean (+/-
      standard deviation) counts were 2.540 +/- 1.026, 2.547 +/- 0.995, and 2.456 +/-
      1.014 log CFU/g for the ISO-VRBG, PF-EB, and automated MPN methods, respectively.
      Mean differences were -0.084 +/- 0.460 log units for the automated MPN results
      compared with the ISO-VRBG and 0.007 +/- 0.450 for the PF-EB results compared
      with the ISO-VRBG results. The automated MPN method tends to yield lower numbers
      and the PF-EB method tends to yield higher numbers than does the ISO-VRBG method
      (difference not significant; Kruskal-Wallis test, P = 0.102). Thus, the average
      difference was highest between the automated MPN method and the PF-EB method (
      0.091 +/- 0.512 log units). Differences between the automated MPN and ISO-VRBG
      results of > 1 log unit were detected in 3.4% of all samples. For 3.9% of the
      samples, one comparison yielded differences of < 1 log CFU/g and the other
      yielded > 1 but < 2 log CFU/g, which means that the differences are possibly > 1
      log CFU/g. For the ISO-VRBG method, confirmation of isolates was necessary to
      avoid a bias due to the presence of oxidase-positive glucose-fermenting colonies.
      The automated MPN system yielded results comparable to those of the confirmed
      Enterobacteriaceae ISO-VRBG method but required only 24 h of analysis time.

PMID- 18326191
TI  - Optimization and validation of a simple method using P22::luxAB bacteriophage for
      rapid detection of Salmonella enterica serotypes A, B, and D in poultry samples.
AB  - A simple method was developed for the fast and inexpensive detection of
      Salmonella Typhimurium using a recombinant P22::luxAB phage. All the steps from
      phage production to detection were considered. A strain of Salmonella Typhimurium
      harboring the prophage P22::luxAB was grown in batch culture to produce
      spontaneously the recombinant bacteriophage. Batch production to stationary phase
      was better for propagation of the phage and led to a total population of 4.3 x
      10(9) (+/-4.3 x 10(9)) PFU/ml of P22, including only 1.4 x 10(6) (+/-1 x 10(6))
      PFU/ml harboring the luxAB genes. After preenrichment, a simple four-step
      bioassay was tested and optimized for several parameters. The detection limit of
      the luminometer was only 5 x 10(2) (+/-1.75 x 10(2)) CFU Salmonella Typhimurium
      per ml, but increased to 1.5 x 10(4) (+/-1.17 x 10(4)) CFU Salmonella Typhimurium
      per ml when the cells were in a complex matrix. The detection limit after the
      preenrichment was 6.5 x 10(3) (+/-1.5 x 10(3)) CFU Salmonella Typhimurium per ml,
      but the detection limit after the preenrichment also increased markedly to 1.65 x
      10(5) (+/-0.15 x 10(5)) CFU Salmonella Typhimurium per ml when Salmonella
      Typhimurium was in a complex matrix. Finally, the bioassay was applied to the
      detection of Salmonella Typhimurium LT2 in 14 different feed and environmental
      samples (including duck feed, litters, and feces) spiked either before or after
      the preenrichment process. It was possible to detect Salmonella Typhimurium LT2
      in all samples within 16 h.

PMID- 18326192
TI  - An evaluation of conventional culture, invA PCR, and the real-time PCR iQ-Check
      kit as detection tools for Salmonella in naturally contaminated premarket and
      retail turkey.
AB  - This study was aimed at comparing the ability of conventional culture, the iQ
      Check real-time PCR kit, and invA PCR to detect Salmonella in naturally
      contaminated premarket and retail turkey parts. Premarket (n = 120) turkey parts
      collected from a commercial turkey processing plant, and retail turkey parts (n =
      138) were examined. Both PCR methods detected a significantly greater (P < 0.05)
      number of positive samples when compared with the conventional culture method for
      the premarket turkey parts. The indices of total agreement between the
      conventional culture method and the iQ-Check kit for the premarket and retail
      parts were 79.2% (95% CI: 70.8, 86) and 90.6% (95% CI: 84.4, 94.9), respectively.
      When the conventional culture method was compared with invA PCR for Salmonella
      detection in the premarket and retail parts, the indices of total agreement were
      75.8% (95% CI: 67.2, 83.2) and 84.1% (95% CI: 76.9, 89.7), respectively. The
      rates of false positives (premarket: 31.9%, retail: 9.7%) and false negatives
      (premarket: 5.9%, retail: 9.7%) were determined between the culture method and
      the iQ-Check kit. When invA PCR was compared with the culture method, the rates
      of false positives (premarket: 37.7%, retail: 11.1%) and false negatives
      (premarket: 5.9%, retail: 18.3%) were obtained. The higher total agreement and
      the lower rates of both false positives and false negatives for the iQ-Check kit
      compared with invA PCR for both premarket and retail turkey parts corroborates
      the use of the iQ-Check kit as a screening tool for Salmonella in poultry meat.

PMID- 18326193
TI  - Detection of group D salmonellae including Salmonella Enteritidis in eggs by
      polymyxin-based enzyme-linked immunosorbent assay.
AB  - A high-throughput, rapid method was devised for the detection of Salmonella
      Enteritidis in egg products. For each target organism, preenrichment in nutrient
      broth was followed by selective enrichment in Rappaport-Vassiliadis soya peptone
      and tetrathionate brilliant green broths or by plating on modified semisolid
      Rappaport Vassiliadis (MSRV) agar medium. The presence of Salmonella Enteritidis
      was determined by subjecting portions of the selective broth cultures or swarming
      growth on MSRV medium to an enzyme-linked immunosorbent assay (ELISA) procedure
      using polymyxin immobilized in the wells of a microtiter plate as a high-affinity
      adsorbent for lipopolysaccharide (LPS) antigens. Sample extracts were reacted
      with polymyxin-coated microwells, and captured LPS antigens were detected
      immunoenzymatically with a commercially available Salmonella factor O9-specific
      antibody. The polymyxin-ELISA was 100% sensitive and 100% specific for Salmonella
      strains bearing the O9 antigen. When the ELISA was combined with enrichment using
      either the selective broths or plating on MSRV medium, the system was an
      effective means for detection of Salmonella Enteritidis in artificially
      inoculated egg products. The polymyxin-ELISA is a simple and inexpensive assay
      for group D salmonellae (including Salmonella Enteritidis) in a convenient 96
      well microtiter plate format, making this system ideally suited for processing
      large numbers of samples.

PMID- 18326194
TI  - Migration of Salmonella Enteritidis phage type 30 through almond hulls and
      shells.
AB  - The ability of Salmonella to migrate from an external aqueous environment through
      the almond hull and shell, and to colonize the kernel, was evaluated in two ways.
      First, the outer surface of shell halves from five varieties of almonds that
      differed in shell hardness were placed in contact with a suspension of Salmonella
      enterica serovar Enteritidis phage type 30 for 24 h at 24 degrees C. Salmonella
      Enteritidis was isolated from the inside of these almond shells in 46 and 100% of
      the samples, by direct swabbing of the inner surface of the shell and by
      enrichment from the swab, respectively. These findings suggested that hardness of
      the shell is not a significant factor in the migration of the pathogen through
      that tissue. In addition, both motile and nonmotile strains of S. enterica
      serovar Typhimurium migrated through the almond shells to the same extent under
      the conditions of this assay, indicating that bacterial migration through the wet
      shell may be a passive process. Second, whole almonds (intact hull, shell, and
      kernel) were soaked for 24 to 72 h at 24 degrees C in a suspension of Salmonella
      Enteritidis phage type 30 labeled with the green fluorescent protein. Green
      fluorescent protein-labeled Salmonella cells were observed on the outer and inner
      surfaces of both the almond hull and shell, and on the kernel, by confocal laser
      scanning microscopy. Our data provide direct evidence that wet conditions allow
      for Salmonella migration through the hull and shell and onto the almond kernel,
      thus providing a means by which almond kernels may become contaminated in the
      field.

PMID- 18326195
TI  - A survey of the bacteriological quality of preroasted peanut, almond, cashew,
      hazelnut, and brazil nut kernels received into three Australian nut-processing
      facilities over a period of 3 years.
AB  - There is little information about bacteriological quality of preroasted kernels
      available in the public domain. An investigation of the bacteriological quality
      of preroasted peanut, almond, cashew, hazelnut, and Brazil nut kernels received
      into three Australian nut-processing facilities was performed over a period of 3
      years. A total of 836 samples were analyzed for aerobic plate count, and 921
      samples for Salmonella and Escherichia coli. The 921 samples included 653 peanut,
      100 cashew, 60 almond, 60 Brazil nut, and 48 hazelnut kernels. There was no E.
      coli detected in any sample. Salmonella subsp. II (Fremantle) was detected in one
      raw almond sample. The aerobic plate count percentages of positive samples with
      counts above the detection level of the plating method used (100 CFU/g) for
      peanuts, almonds, cashews, hazelnuts, and Brazil nuts were 84, 78, 74, 50, and
      45%, respectively. Of the samples containing more than this detection limit, the
      means were 4.5, 4.4, 3.1, 2.5, and 3.8 log CFU/g respectively. Although roasted
      kernel quality was not within the scope of this survey, raw microbial bioload
      would be expected to reduce on roasting. The bacteriological quality of
      preroasted peanut, almond, cashew, hazelnut, and Brazil nut kernels received into
      nut-processing facilities in Australia does not appear to suggest a public health
      concern.

PMID- 18326196
TI  - Effect of xylitol on adhesion of Salmonella Typhimurium and Escherichia coli
      O157:H7 to beef carcass surfaces.
AB  - Effects of 10% xylitol (a five-carbon sugar alcohol) on adhesion of Escherichia
      coli O157:H7 and Salmonella Typhimurium to meat surfaces were examined with three
      approaches. First, beef outside round was inoculated with rifampin-resistant E.
      coli O157:H7 and Salmonella Typhimurium dispersed in xylitol or peptone solution.
      Samples were rinsed with water or not rinsed in a 2 x 2 factorial arrangement. No
      interaction existed between inoculum and rinsing treatments (P > 0.84).
      Incubation in xylitol had minimal impact on pathogen adhesion (P > 0.76);
      however, rinsing reduced pathogen cell counts (P < 0.01). Second, meat samples
      were treated with water, xylitol, or no rinse; inoculated with pathogens
      dispersed in peptone solution (8.6 log CFU/ml for each pathogen); and then
      treated with water, xylitol, or no rinse in a 3 x 3 factorial arrangement. No
      interactions were observed (P > 0.50). Postinoculation rinsing reduced pathogen
      loads (P < 0.01) without difference between water and xylitol (P > 0.64). Third,
      carcass surfaces inoculated with pathogens (5.5 log CFU/cm2) were treated with 35
      degrees C water wash, 2.5% L-lactic acid spray, 10% xylitol spray, lactic acid
      plus xylitol, or hot water plus xylitol. Lactic acid treatments reduced
      Salmonella Typhimurium at 0 h (P < 0.01) and 24 h (P < 0.02). Hot water
      treatments tended to reduce Salmonella Typhimurium at 0 h (P < 0.07). Xylitol did
      not reduce pathogens (P > 0.62) or increase effectiveness of other treatments.
      Xylitol does not influence E. coli O157:H7 and Salmonella Typhimurium adhesion to
      meat surfaces.

PMID- 18326197
TI  - Antibacterial activity of dextran-conjugated lysozyme against Escherichia coli
      and Staphylococcus aureus in cheese curd.
AB  - The purposes of this research were to glycosylate lysozyme with dextran under
      Maillard reaction conditions and assess the antimicrobial characteristics of the
      lysozyme-dextran conjugate in a culture medium and cheese curd. Solutions
      containing lysozyme and dextran were incubated at 60 degrees C and at 79%
      relative humidity. Gel permeation chromatography and sodium dodecyl sulfate
      polyacrylamide gel electrophoresis were used to follow the glycosylation process.
      Under optimum conditions 3.7 mol of dextran were coupled to 1 mol of lysozyme.
      Lytic activity of the conjugate against the cell wall of Micrococcus luteus was
      about 62% of that of native lysozyme. Evaluation of the lysozyme-dextran
      conjugate against test microorganisms (Staphylococcus aureus and Escherichia
      coli) in culture media indicated a progressive increase in antimicrobial
      activity, with an increase in enzyme-conjugate concentration. The lysozyme
      dextran conjugate was also effective against E. coli in a natural food system, as
      it reduced the bacterial count by 3 log in cheese curd after 40 days of storage.
      Unlike E. coli, the antimicrobial action of lysozyme against S. aureus was not
      improved by conjugation with dextran in both in vitro and in vivo tests.
      Antimicrobial activity of the lysozyme-dextran conjugate against gram-negative
      bacteria is probably related to the remaining lytic activity as well as the
      excellent surfactant properties of the lysozyme-dextran conjugate. These results
      might increase the applicability of lysozyme as a natural antimicrobial
      ingredient in different food products.

PMID- 18326198
TI  - Characterization of the low-salinity stress in Vibrio vulnificus.
AB  - Vibrio vulnificus is a marine pathogenic bacterium commonly found in seawater or
      seafood. This organism encounters low-salinity stress in its natural environment
      and during food processing. This study was designed to investigate the response
      of V. vulnificus YJ03 to lethal low salinity (0.04% NaCl) and its adaptation to
      sublethal salinity (0.12% NaCl with 20 amino acids added). A short period in the
      nonculturable state was induced by lethal low-salinity stress followed by cell
      death after 30 min of stress. Addition of 1 mM glycine betaine or 0.5 mM sucrose
      reduced the damage. Low-salinity adaptation was achieved in the exponential-phase
      cells but not in the stationary-phase cells. Significant protection against
      lethal low-salinity stress was attained when the cells were adapted for as little
      as 1.5 min. The adapted cells were significantly protected against lethal low
      salinity and 2.4% sodium sorbate but sensitized to the challenge of heat (52
      degrees C) and acid (pH 3.2). Nonlethal low-salinity treatment of seafood should
      be avoided to prevent stress adaptation of V. vulnificus.

PMID- 18326199
TI  - Contributions of two-component regulatory systems, alternative sigma factors, and
      negative regulators to Listeria monocytogenes cold adaptation and cold growth.
AB  - The ability of Listeria monocytogenes to grow at refrigeration temperatures is
      critical for transmission of this foodborne pathogen. We evaluated the
      contributions of different transcriptional regulators and two-component
      regulatory systems to L. monocytogenes cold adaptation and cold growth. L.
      monocytogenes parent strain 10403S and selected isogenic null mutants in genes
      encoding four alternative sigma factors (sigB, sigH, sigC, and sigL), two
      regulators of sigmaB (rsbT and rsbV), two negative regulators (ctsR and hrcA),
      and 15 two-component response regulators were grown in brain heart infusion broth
      at 4 degrees C with (i) a high-concentration starting inoculum (10(8) CFU/ml),
      (ii) a low-concentration starting inoculum (102 CFU/ml), and (iii) a high
      concentration starting inoculum of cold-adapted cells. With a starting inoculum
      of 10(8) CFU/ml, null mutants in genes encoding selected alternative sigma
      factors (DeltasigH, DeltasigC, and DeltasigL), a negative regulator (DeltactsR),
      regulators of sigmaB (DeltarsbT and DeltarsbV), and selected two-component
      response regulators (DeltalisR, Deltalmo1172, and Deltalmo1060) had significantly
      reduced growth (P < 0.05) compared with the parent strain after 12 days at 4
      degrees C. The growth defect for DeltasigL was limited and was not confirmed by
      optical density (OD600) measurement data. With a starting inoculum of 102 CFU/ml
      and after monitoring growth at 4 degrees C over 84 days, only the DeltactsR
      strain had a consistent but limited growth defect; the other mutant strains had
      either no growth defects or limited growth defects apparent at only one or two of
      the nine sampling points evaluated during the 84-day growth period (DeltasigB,
      DeltasigC, and Deltalmo1172). With a 10(8) CFU/ml starting inoculum of cold
      adapted cells, none of the mutant strains that had a growth defect when
      inoculation was performed with cells pregrown at 37 degrees C had reduced growth
      as compared with the parent strain after 12 days at 4 degrees C, suggesting a
      specific defect in the ability of these mutant strains to adapt to 4 degrees C
      after growth at 37 degrees C. Our data indicate (i) selected sigma factors and
      two-component regulators may contribute to cold adaptation even though two
      component regulatory systems, alternative sigma factors, and the negative
      regulators CtsR and HrcA appear to have limited contributions to L. monocytogenes
      growth at 4 degrees C in rich media, and (ii) inoculum concentration and
      pregrowth conditions affect the L. monocytogenes cold-growth phenotype.

PMID- 18326200
TI  - Heat shock induces barotolerance in Listeria monocytogenes.
AB  - The aim of this study was to investigate the effect of heat shock on the
      resistance of Listeria monocytogenes to high pressure processing (HPP). L.
      monocytogenes ATCC 19115 was grown to stationary phase at 15 degrees C and
      inoculated into whole ultrahigh-temperature milk at approximately 10(7) CFU/ml.
      Milk samples (5 ml) were placed into plastic transfer pipettes, which were heat
      sealed and then heated in a water bath at 48 degrees C for 10 min. Immediately
      after heat shock, the milk was cooled in water (20 degrees C) for 25 min and then
      placed on ice. The samples were high pressure processed at ambient temperature
      (approximately 23 degrees C) at 400 MPa for various times up to 150 s. Following
      HPP, the samples were spread plated on tryptic soy agar supplemented with yeast
      extract. Heat shock significantly increased the D400 MPa-value of L.
      monocytogenes from 35 s in non-heat-shocked cells to 127 s in heat-shocked cells
      (P < 0.05). Addition of chloramphenicol before heat shock eliminated the
      protective effect of heat shock (P < 0.05). Heat shock for 5, 10, 15, or 30 min
      at 48 degrees C resulted in maximal barotolerance (P < 0.05); increasing the time
      to 60 min significantly decreased survival compared with that at 5, 10, 15, or 30
      min (P < 0.05). These results indicate that prior heat shock significantly
      increases the barotolerance of L. monocytogenes and that de novo protein
      synthesis during heat shock is required for this enhanced barotolerance.

PMID- 18326201
TI  - Survival rate analysis of freeze-dried lactic acid bacteria using the arrhenius
      and z-value models.
AB  - The survival rate of five freeze-dried bacteria species, Lactobacillus plantarum,
      Lactobacillus pentosus, Weisella paramesenteroides, Leuconostoc mesenteroides,
      and Lactobacillus fermentum, was described in terms of reaction rate constants (D
      or k) and temperature sensitivity of rate constants (z or Ea). The freeze-dried
      strains were stored under vacuum at 55, 37, and 4 degrees C for 168 h, 17 days,
      and 2 months, respectively. D-values decreased and k increased with an increase
      of the storage temperature. Neither the z-value nor the inactivation energy (Ea)
      of the reaction was significantly different (P > 0.05) for all the strains,
      suggesting that thermal inactivation of the freeze-dried lactic acid bacteria may
      occur by the same mechanism. Therefore, it was possible to compare rate constants
      of survival for the freeze-dried strains studied.

PMID- 18326202
TI  - Potential of houseflies to contaminate ready-to-eat food with antibiotic
      resistant enterococci.
AB  - It was shown previously that houseflies in fast-food restaurants commonly carry
      antibiotic-resistant and potentially virulent enterococci. In this study, the
      potential of field-collected houseflies to contaminate ready-to-eat (RTE) food
      with enterococci was assessed by laboratory bioassays. Houseflies were collected
      with a sweep net in a cattle feedlot and exposed in groups of 5, 10, 20, and 40
      to a beef patty (from an RTE hamburger) for 0.5, 1.0, 3.0, and 24 h. The exposure
      of RTE food to flies resulted in 100% contamination with enterococci in all
      bioassays, regardless of the number of houseflies and the length of exposure
      time. In addition, with the increasing number of houseflies as well as with the
      increasing time exposure, the concentration of enterococci in RTE food increased.
      Even a short time exposure (0.5 h) resulted in food contamination, ranging from
      3.1 x 10(3) CFU/g (5 houseflies) to 8.4 x 10(4) CFU/g (40 houseflies). The
      analysis of 23 randomly selected enterococcal isolates from RTE food after the
      fly exposure revealed a single species, Enterococcus faecalis. In contrast, four
      Enterococcus species, including E. faecalis (57.1%), E. gallinarum (19.1%), E.
      hirae (14.3%), and E. faecium (9.5%), represented 21 randomly selected and
      identified isolates from houseflies. Phenotypic screening showed that E. faecalis
      isolates from RTE food were resistant to ciprofloxacin (17.4%), tetracycline
      (13.0%), erythromycin (13.0%), and chloramphenicol (4.3%). This study
      demonstrates a great potential of houseflies from a cattle feedlot to contaminate
      RTE food with enterococci in a short time.

PMID- 18326203
TI  - Constraints in meeting food safety and quality requirements in the Turkish dairy
      industry: a case study of Izmir province.
AB  - Recent global developments concerning food quality and food safety have
      influenced and stimulated food legislation in Turkey in accordance with internal
      and international trade and agreements. In this study, the way in which the dairy
      industry conforms to this legislation was analyzed through a case study of Izmir
      province, which generally has all the structural characteristics of the dairy
      sector in Turkey. A survey in which dairy plant managers responded to a special
      questionnaire was used to collect data from 86 dairy plants chosen on the basis
      of proportional sampling. According to the results of this study, (i) there are
      many dairy processors in the region, (ii) most managers have a limited education
      concerning their positions, (iii) most firms handle small volumes of milk and
      have little control over the raw milk supply, (iv) resources are too limited in
      these firms, limiting their ability to adopt most regulations, and (v) few
      processors apply the regulatory practices imposed by governmental agencies. Thus,
      food legislation is not enough to ensure food safety in the dairy industry in
      Turkey. Technical and educational support should be given to farmers and the
      staff of dairy firms by the Ministry of Agriculture to form an appropriate food
      safety infrastructure in Turkey for the milk and processed dairy products
      industry.

PMID- 18326204
TI  - Cleaning and other control and validation strategies to prevent allergen cross
      contact in food-processing operations.
AB  - Food allergies affect an estimated 10 to 12 million people in the United States.
      Some of these individuals can develop life-threatening allergic reactions when
      exposed to allergenic proteins. At present, the only successful method to manage
      food allergies is to avoid foods containing allergens. Consumers with food
      allergies rely on food labels to disclose the presence of allergenic ingredients.
      However, undeclared allergens can be inadvertently introduced into a food via
      cross-contact during manufacturing. Although allergen removal through cleaning of
      shared equipment or processing lines has been identified as one of the critical
      points for effective allergen control, there is little published information on
      the effectiveness of cleaning procedures for removing allergenic materials from
      processing equipment. There also is no consensus on how to validate or verify the
      efficacy of cleaning procedures. The objectives of this review were (i) to study
      the incidence and cause of allergen cross-contact, (ii) to assess the science
      upon which the cleaning of food contact surfaces is based, (iii) to identify best
      practices for cleaning allergenic foods from food contact surfaces in wet and dry
      manufacturing environments, and (iv) to present best practices for validating and
      verifying the efficacy of allergen cleaning protocols.

PMID- 18326205
TI  - [Scientific-and-Practical Conference on Sarcoidosis: diagnosis, clinical picture,
      treatment, and follow-up].

PMID- 18326206
TI  - [Morbidity of adult contacting persons in the family foci of tuberculosis and
      impact of aggravating factors].
AB  - Eighty-three foci of infection were studied in 2 communities of Yerevan (a study
      group) in which of 279 contact persons, 117 (40.2%) adult family members had
      fallen ill over 10 years (1995-2005); of them there were 61 (32.5%) persons, with
      2 and 3 subjects in 20 and 7 (only type 1 foci) foci, respectively. There was a
      preponderance of type 1 foci that were most unfavorable in infection massiveness
      and hygiene and sanitary conditions, in which the largest number of contacting
      persons (62.4%) had been fallen. Among the sources of infection, males (84.3%),
      able-bodied (aged 31-50 years) (47%), and patients with destructive bacterial
      forms of pulmonary tuberculosis (85.55%) were prevalent; 19.3% isolated drug
      resistant Mycobacterium tuberculosis (MBT) strains and 20.4% died. All the above
      aggravating factors were significantly more frequently encountered in than in the
      control group comprising 50 foci with 110 family members and none case of the
      disease (p < 0.05). Among the diseased contacting persons, the young (18-30-year
      old) (43.6%) and able-bodied (40.2%) were predominant. Sex-specific differences
      were not established. Out of the clinical forms, infiltrative and focal foci
      prevailed. The disease was detected in 62.4% following 6 months or more and in
      the remaining with a better pattern in the earlier period (within 1 to 6 months),
      which shows it necessary to reduce the time of a follow-up from 6 to 3 months.
      Identification of 13.7% of the contacting persons simultaneously with the source
      of infection requires that detection of latent foci of infection should be
      improved.

PMID- 18326207
TI  - [Use of natural physical factors in the rehabilitative treatment of patients with
      chronic obstructive pulmonary diseases].
AB  - The paper presents the results of using sylvinite speleotherapy, general salt
      baths and their combination in 120 patients with Stages I-II chronic obstructive
      pulmonary disease at a damped exacerbation and remission. It is shown that in the
      patients with this disease treated by the above procedures, the inflammatory
      process regresses, bronchial patency, central hemodynamics, exercise performance,
      and psychoemotional background improves and, during a long-term followup, the
      progression of the disease becomes slower, remissions prolong, exercise
      performance increases, and social adaptation improves.

PMID- 18326208
TI  - [Approach to diagnosing tuberculosis of intrathoracic lymph nodes of a paraaortic
      group in children].
AB  - A hundred and seventeen patients aged 3 to 14 years, with suspected tuberculosis
      of intrathoracic lymph nodes (ILN) of a paraaortic group in the phase of
      calcination, were examined at the Clinic of Childhood Pulmonary Tuberculosis,
      Saint Petersburg Research Institute of Phthisiology. The comprehensive
      examination made the diagnosis of tuberculosis be cancelled in 35% of cases and
      confirmed in 65%, by determining the phase and extent of a specific inflammation.
      In 8.5% the local manifestations of the disease were absent along with the
      significant symptoms of intoxication and with the activity of tuberculous
      infection, which gave grounds to establish the diagnosis of tuberculous
      intoxication. Despite the fact that computed tomography revealed aortic ligament
      calcification, enlarged mediastinal lymph nodes were detected in 35%. High
      tuberculous infection activity and mediastinal ILN lesion in different phases of
      the specific inflammation were found in 15.4%, which was indicative of the
      chronic course of inflammation. The first detected isolated calcification in the
      paraaortic group of lymph nodes was diagnosed in 5.9%. The use of the presented
      complex, the diagnostic efficiency of which was 98%, significantly enhanced the
      diagnosis and reduced the number of errors in making the diagnosis.

PMID- 18326209
TI  - [Risk factors and their impact on disseminated forms of tuberculosis in
      adolescents].
AB  - The authors have analyzed 298 case histories of 14-18-year-old adolescents
      treated at the Childhood and Adolescence Department, Research Institute of
      Phthisioplmonology for new-onset pulmonary tuberculosis in 1996 to 2005. In 2001
      2005 versus 1996-2000, circumscribed tuberculosis became to occur significantly
      less frequently while disseminated tuberculosis did significantly more frequently
      (by 3.3-fold). The number of bacteria-discharging persons proportionally
      increased (by 3.3-fold). Late detection of the disease is one of the principal
      causes of disseminated forms of tuberculosis in adolescents. The reasons for
      untimely examination of the examines who had contacted were their striking-off
      the register 1-3 years before detection of the disease in 32.4% of cases and the
      adolescents' unestablished contacts with bacteria-discharging persons in 27.8% of
      cases. In 86.2% of cases, the general practitioners had not made a goal-oriented
      examination of the adolescents admitted to the general health care network for
      signs of suspected tuberculosis.

PMID- 18326210
TI  - [Estimation of the specific sensitization in a child and other immunological
      parameters in tuberculosis of intrathoracic lymph nodes during therapy].
AB  - The data of a comprehensive study of 86 children aged 6 to 14 years, who were
      examined and treated at the Research Institute of Phthisiology for various
      manifestations of tuberculous infection: 25.6% with infected Mycobacterium
      tuberculosis with varying specific sensitization; 34.9% with minor forms of
      intrathoracic lymph node tuberculosis (ILNT), and 39.5% with disseminated
      processes into the intrathoracic lymph nodes. RM V, VI, VII, and VIII dilutions
      are of the greatest informative value in the determination of the activity of
      tuberculous infection. Most children with ILNT showed a significant cellular
      response to PPD in the LBT test, The LCT test revealed that neutrophilic
      granulocytes were functionally inadequate in all the children. The currently
      available immunological tests used in combination with the existing methods
      adequately evaluate the activity of tuberculous infection in children.

PMID- 18326211
TI  - [Diagnostic and treatment policy errors in caseous pneumonia].
AB  - Analysis of diagnostic and treatment policy in 314 patients with caseous
      pneumonia has identified a complex of factors that considerably affect the
      outcome of the disease. The most significant diagnostic errors are a considerable
      delay of out- and inpatient diagnosis, untimely determination of caseous
      pneumonia as a form of tuberculosis under the conditions of tuberculosis
      institutions. Drug treatment errors involve the wrong determination of the goal
      of treatment to hopefully eliminate destructions, as well as inadequate
      etiopathogenetic therapy. The points are long-term preparation for surgical
      treatment and a low proportion of caseous pneumonia patients operated on.
      Strategic and tactical errors have been ascertained to be of great importance in
      defining a place of surgical treatment in the general plan of treatment for
      patients with caseous pneumonia.

PMID- 18326212
TI  - [Primary drug resistance in Mycobacterium tuberculosis among patients with
      pulmonary tuberculosis and its impact on permanent disability in the Volgograd
      region].
AB  - In the past 5 years, there has been a rise in the number of patients with new
      onset drug-resistant pulmonary tuberculosis from 32.3% to 44.0%. The pattern of
      primary resistance is marked by an increase in the proportion of multidrug
      resistant Mycobacterium tuberculosis (MBT) strains, by the steady-state level of
      their isolation, and by a reduction in the detection rate of unidrug resistant
      strains. The efficiency of treatment in pulmonary tuberculosis patients with
      primary MBT resistance depends on patient compliance. After 3-year follow-up,
      death occurred in 12.2% of the patients, the tuberculous process became chronic
      in 31.7%, and there was a relapse in 9.8%. The drug resistance of the causative
      agent affects the duration of disability due to tuberculosis to a greater extent
      than does multidrug resistance.

PMID- 18326213
TI  - [Neuropsychic state in convicts with tuberculosis at different penitentiaries].
AB  - The neuropsychic studies in convicts suggest that human exposure to multiple
      factors induces a severe acute stress that accordingly results in neuropsychic
      disorders and in more significant disruption of the body's performance. Due to
      the fact that tuberculosis occupies a certain place among all diseases; learning
      about his being ill becomes a much stronger psychotraumatizing factor to the
      convict. A combined exposure to various factors, including the disease itself,
      influences convicts' emotional reaction and has serious personality consequences
      that appear as altered mental state and limited social activity; as well as
      difficult adaptation to new living conditions and all these factors substantially
      influence the course and outcome of the disease.

PMID- 18326214
TI  - [Pathomorphological features of pulmonary tuberculosis at different stages of HIV
      infection: autopsy data].
AB  - The case histories, autopsy protocols, and histological specimens from 11
      patients who had died from HIV-associated tuberculosis and 15 patients died from
      progressive disseminated tuberculosis and caseous pneumonia in the absence of HIV
      infection (a control group). In all the study patients, the morphology of the
      lung and peripheral and intrathoracic lymph nodes was examined at the early (2B)
      and late (4B-5) stages of HV infection (Groups 1 and 2, respectively). Group 1
      patients had died from caseous pneumonia. Their morphology of tuberculosis
      differed little from that in the control group. Group 2 was marked by a
      predominance of disseminated tuberculosis with extensive exudative necrotic
      lesions in the lung, lymph nodes, and other organs in the presence of reduced
      lymphoid tissue and in the absence of a limited epitheloid cell reaction.

PMID- 18326215
TI  - [Structure of deletions detected in the genomes of clinical Mycobacterium
      tuberculosis strains].
AB  - Deletions were analyzed in the genomes of four Mycobacterium tuberculosis strains
      isolated from the sputum of patients living in the Central Region of Russia. The
      strains of the Beijing family were found to have deletions affecting 40 open
      reading frames (ORF) and to amount to 0.7% of the genome H37Rv. Genome deletions
      in a strain from the Haarlem family affected 20 ORF and accounted for 0.26% of
      the genome H37Rv. Six of the eight deletions were located at the site of
      preferred cloning on the insertion element IS6110. Prophage phiRv1-associated
      deletion sequence 149 is the only common to the strains of both families. The
      deletion ends were evenly distributed among the intergenic and coding chromosome
      regions with an insignificant preference of the latter. The authors revealed a
      new deletion in strain 1540 belonging to the Haarlem family and a two-component
      deletion in the region RvD2. The deletions detected in the genomes of Russian
      Beijing strains were typical of strains from South-East Asian countries.

PMID- 18326216
TI  - [Epidemiological features of antibiotic resistance in Streptococcus pneumoniae
      strains isolated from patients with pneumococcal pneumonias].
AB  - Despite advances in the diagnosis and treatment of pneumococcal infections,
      effective antibiotic therapy for pneumococcal pneumonias remains to be a topical
      problem. The investigation was undertaken to study the specific features of
      development of antibiotic resistance in S. pneumoniae strains isolated in
      patients with pneumococcal pneumonias. In the Primorye Territory, pneumococcal
      pneumonia mortality rates were established to be 32.73 +/- 1.58 (28.98-36.48) per
      10,000. At the same time the major portion of drug-resistant strains was those
      that were resistant to trimetroprim- sulfamethoxazole (52.34%), tetracycline
      (58.4%), clindamycin (32.88%), erythromycin (12.08%), and ciprofloxacin (12.75%).
      The increase in the number of pneumococcus strains resistant to macrolides and
      fluoroquinolones in the age group of 5 to 18 ages allows one to recommend that
      the use of drugs of these groups be improved first of all in patients of this age
      who have invasive forms of pneumococcal infections.

PMID- 18326217
TI  - [Organization of antituberculosis care at the municipal level. Section 3.
      "Chemotherapy for tuberculosis"].

PMID- 18326218
TI  - [National program "National Health" and advanced medical training of therapists
      in district outpatient clinics].

PMID- 18326219
TI  - [Radionuclide diagnosis of functional pulmonary disorders in outpatient setting].
AB  - AIM: To define informative value of a novel technique in radionuclide examination
      of microcirculatory and alveolar ventilation disorders in pulmonary diseases and
      to test its application possibilities in outpatient practice. MATERIAL AND
      METHODS: Perfusion static scintigraphy of the lungs with 99m-Tc-macrotech and
      ventilatory aerosol dynamic and static pulmonary scintigraphy after 99m-Tc
      pentatech (DTPA analogue) inhalation were performed in 128 patients with
      bronchial asthma (BA), chronic obstructive bronchitis (COB) and pulmonary
      abscess. RESULTS: Regional perfusion and ventilation were abnormal in all the
      examinees with BA and COB including in lower zones of both the lungs
      characteristic of pulmonary emphysema. In COB ventilation-perfusion correlations
      were disturbed in both lungs in 87.5%, in one lung in 100% patients. In BA
      patients after the attack the results of ventilatory pulmonary scintigraphy
      should be evaluated visually (qualitatively). In pulmonary abscess regional
      disorders of perfusion and/or ventilation were seen in 94.6%, lack of balance V/Q
      in the focal zone--in 75%, in the whole affected lung--in 55.4% patients.
      Compensatory synchrony of ventilation-perfusion relations in impaired regional
      indices V/Q took place in COB patients in 37.5%, in abscess (in the affected
      lung)--in 42.9%. Acceleration and delay of alveolar-capillary diffusion were
      detected in bronchial asthma in 76.5%, COB--in 68.7%, in abscess in the affected
      lung--in 48.8%, in the contralateral lung--in 56.5%. CONCLUSION: Lung lesion can
      be assessed with ventilation-perfusion correlations and clearance of 99mTc
      pentatech from the right and left lung.

PMID- 18326220
TI  - [Real possibilities of stroke risk reduction in long-term treatment of arterial
      hypertension with calcium antagonists (lecture)].

PMID- 18326221
TI  - [Optimization of treatment of outpatients and inpatients with bronchial asthma in
      the Samara region].
AB  - AIM: To identify factors influencing hospitalization rate of bronchial asthma
      (BA) patients for optimization of medical care for BA patients, improvement of
      hospital-outpatient clinic succession. MATERIAL AND METHODS: Personal benefit
      drug data base of the Samaia region was used for monitoring of pharmacotherapy
      quality in 19,697 BA patients aged 17 years and older. The list of the prescribed
      anti-asthmatic drugs was compared to some indices of medical care quality. The
      data were analysed with the multifactorial analysis. RESULTS: The multifactorial
      analysis has shown that BA patients' hospitalization rate depends on the
      structure of pharmacotherapy, especially optimal administration of basic drugs. A
      model of effective pharmacotherapy of BA patients on the out- and inpatient
      stages of medical care is proposed. CONCLUSION: Regional standards allowed
      general practitioners to give effective therapy in BA, hospital physicians to
      formulate recommendations for patients after hospital treatment.

PMID- 18326222
TI  - [Mechanism of action of Nizhne-Ivkinskaya 2K sulfate-calcium mineral water in
      combined treatment of acid-dependent gastrointestinal diseases].
AB  - AIM: To study efficacy of drinking mineral water (MW) nizhne-ivkinskaya 2K in
      combined sanatorium treatment of gastrointestinal acid-dependent diseases (ADD)
      and the role of endogenic modulators of M-cholinoreactivity in pathogenesis of
      ADD. MATERIAL AND METHODS: General condition of the patients, gastric pH and
      peristalsis (computer system Gastrolog-M), gastric and gall bladder motility
      (Aloka SSD 1100), hepatic function (by bilirubin and AST and ALT activity), lipid
      spectrum (including LDLP and HDLP) and M-cholinomodulating activity of the blood
      serum (by biomethod) were examined in 134 subjects: 20 healthy subjects and 114
      patients with ADD. RESULTS: In ADD, gastric juice acidity is high, gastric and
      gall bladder motility is low, total cholesterol and LDLP cholesterol are
      elevated, M-cholinoblocking activity of the blood serum is reduced 10-fold.
      Intake of nizhne-ivkinskaya 2K mineral water for 21 days improved the patients'
      health, normalized gastric pH, motility of the stomach and gall bladder, reduced
      content of LDLP and restored M-cholinoblocking serum activity. CONCLUSION: ADD
      development is thought to result from excessive vagus effect due to elevated
      blood level of lysophosphatidylcholine (LPC). In certain concentrations it can
      enhance efficacy of M-cholinergic impacts on gastric cells. Reduction of LDLP
      content due to intake of the mineral water leads to normalization of M
      cholinergic impacts on gastric cells.

PMID- 18326223
TI  - [Medical rehabilitation and follow-up of patients with yersiniosis].

PMID- 18326224
TI  - [Prognostic significance of typical immune reactions in myocardial infarction].
AB  - AIM: To ascertain the role of typical reactions of the immune system in early
      prognostication of congestive cardiac failure (CCF) in patients with primary
      transmural anterior myocardial infarction (MI) in the postinfarction period.
      MATERIAL AND METHODS: Typical immune reactions were studied for a year after the
      disease onset. A total of 228 males aged 40-60 years (mean age 53.8 +/- 4.1
      years) with primary Q-wave MI of anterior location without accompanying diseases
      or allergy, with comparable volumes of myocardial necrosis were included in the
      trial. The control group consisted of 35 healthy men aged 40 to 60 years (mean
      age 52.9 +/- 4.3 years). Morphofunctional characteristics of the heart were
      studied by Doppler echocardiography within a month since MI onset and a year
      after MI. Immunological examination performed on MI day 1, 15 and 25 included
      determination by tests of the first-second level by R. V. Petrov of the count of
      leukocytes, lymphocytes, T-cells, T-helpers, T-suppressors (CD3+, CD4+, CD9+),
      zero lymphocytes, immunoglobulins, circulating immune complexes, complement by
      50% hemodialysis, phagocyte index and count. Statistical processing included
      parametrical and non-parametrical criteria, correlation-regression analysis,
      criterion chi-square. The index of diagnostic significance Kj was calculated.
      Also, frequency and graphic analyses were made. RESULTS: The analysis of
      immunological disorders in patients with five variants of primary Q-wave MI (LV
      aneurism with moderate dilatation of the cavity, aneurism of the heart in
      combination with L V cavity dilation with CDR >60 mm and development of mitral
      regurgitation >2 degrees, prevalence of LV diastolic dysfunction, progressive
      dilatation of the heart cavities with development of mitral of degree 2-3 and
      tricuspidal of degree 1-2 insufficiency, compensated hemodynamics without
      essential changes of the LV and LA) has established the same type of immune
      reactions to the pathological process manifesting with a fall in the count of
      absolute and relative count of lymphocytes, T-cells, T-helpers, B-lymphocytes,
      complement, phagocytic index, suppression index. These changes were accompanied
      with increased count of T-suppressors, zero-lymphocytes, CIC, immunoglobulins,
      leucointoxication index. The immunological examination of the patients showed
      that all morphofunctional variants of the myocardium correlated with suppression
      of immune reaction in the following order: compensated aneurism of the LV (18
      parameters), diastolic dysfunction of the LV (11), progressive dilatation of the
      heart cavities (8), aneurism of the LV (6), marked dilatation of the heart
      cavities (4). Patients with pronounced dynamics of the regenerative processes had
      suppression of cellular immunity of the second degree, in positive hemodynamics
      there were characteristic changes in T-suppressor link of immunity in
      accumulation of zero lymphocytes. Patients with poor outcome of primary Q-MI had
      the same formula of immune parameters: reduced count of T-helpers, high values of
      T-suppressors and CIC. Thus, the data show that low count of T-helpers, common T
      cells, high level of T-suppressors or zero-cells during post-MI month 1 are
      related with compensated regeneration of the cardiac muscle. If the patients have
      deviation of the regulatory index and accumulation of CIC, they have poor
      prognosis. Regarding the time since MI (1, 15 or 25 days), the following
      regulation was seen: patients with compensated hemodynamics have 4 decreased and
      1 increased parameters of immune status; patients with pathological myocardial
      remodeling have stimulation of at least 5-6 parameters of the immune status.
      CONCLUSION: Myocardial remodeling of the LV proceeds within the first year after
      development of myocardial necrosis; outcomes of myocardial restoration correlate
      with severity of immune disorders forming 2-3 weeks after MI, suppression of cell
      reactions agrees with compensated hemodynamics; accumulation of CIC in blood
      points to the risk of pathological remodeling of the left ventricle and post-MI
      cardiac failure.

PMID- 18326225
TI  - [Changes in parameters of orthogonal ECG in hypertensive patients given combined
      antihypertensive treatment].
AB  - AIM: To evaluate changes in parameters of orthogonal ECG in hypertensive patients
      on trandolapril+verapamil combination. MATERIAL AND METHODS: Eighteen patients
      before and after 8-week therapy were examined using orthogonal ECG and 24-h
      monitoring of blood pressure. Computer processing of orthogonal ECG was made with
      calculation of some vectorcardiography (VCG) and d mapping parameters. Also, 24-h
      blood pressure monitoring was made. RESULTS: 8-week therapy significantly reduced
      mean diurnal and nocturnal systolic and diastolic blood pressure (SBP, DBP),
      improved their variability. In patients with VCG signs of left ventricular
      hypertrophy the treatment significantly diminished some VCG parameters. A direct
      correlation was found between initial diurnal SBP variability and SQRSxyz,
      SQRSxz; dynamics of nocturnal SBP variability and dynamics of SQRSxyz, SQRSxz and
      Rx+Sz (r = 0.7; p < 0.05). A direct correlation was between dynamics of SBP and
      IADI (r = 0.7; p < 0.05). CONCLUSION: Hypertensive patients treated with a fixed
      combination trandolapril/verapamil exhibit a positive trend not only in
      parameters of 24-h monitoring of blood pressure but also in parameters of
      orthogonal ECG.

PMID- 18326226
TI  - [Nibentan in arresting acute atrial fibrillation: risk or benefit?].
AB  - AIM: To study efficacy and safety of using a domestic anti-arrhythmic drug
      nibentan for arresting acute atrial fibrillation. MATERIAL AND METHODS: A total
      of 210 patients received nibentan in a dose 0.125 mg/kg dissolved in 20.0 ml of
      0.9% sodium chloride solution by intravenous slow jet 3-min injection. In no
      response, the injection was repeated 20 min later. Nibentan injection was
      accompanied with continuous ECG monitoring, measurements of QT interval, arterial
      pressure. The criterion of efficacy was atrial fibrillation conversion into the
      sinus rhythm within 24 hours after injection of a total nibentan dose. RESULTS:
      Nibentan in a dose 0.125 mg/kg demonstrated high efficacy (91.9%) and sufficient
      safety (incidence of polymorphic ventricular tachycardia 2.4%) including patients
      taking other antiarrhythmic drugs. A basic marker of an electrophysiological
      effect of nibentan on the myocardium is a dynamic change in the interval QT which
      may serve a predictor of sinus rhythm reestablishment (in QT > or =480 ms) and of
      a risk to develop proarrhythmogenic complications (in QT > or =640 ms).

PMID- 18326227
TI  - [Impact of diabetes mellitus on other cardiovascular risk factors in patients
      with stenosis of the internal carotid artery].
AB  - AIM: To examine cardiovascular risk factors, clinical features and their impact
      on the results of carotid endarterectomy in diabetic patients with stenosis of
      the internal carotid artery. MATERIAL AND METHODS: We analysed data on 100
      diabetic and 607 nondiabetic patients who underwent carotid endarterectomy in
      Vilnius University Emergency hospital from 1995 through 2005. RESULTS: Diabetic
      patients with carotid artery stenosis were younger (p < 0.05), they smoked less
      often (p < 0.001) and were more often obese (p < 0.001) than nondiabetic
      patients. 93% of diabetic patients had arterial hypertension or
      hypercholesterolemia or even more cardiovascular risk factors. Diabetic were more
      likely to have nonspecific symptoms and severe bilateral carotid stenosis (p <
      0.01). Perioperative stroke and mortality rate was 12% for diabetic and 3.4% for
      nondiabetic patients (p < 0.001), but no perioperative myocardial infarction was
      identified in diabetic patients. Four clinical factors increased the odds of
      complications: age 75 > (odds ratio--OR 2.2; 95% confidence interval--CI 1-4.9),
      smoking (OR 2.7, 95% CI 1.8-4.2), obesity (OR 6.1; 95% CI 3.9-9.5) and severe
      bilateral carotid stenosis (OR 2.1; 95% CI 1.3-3.6). CONCLUSION: Diabetes
      mellitus in patients with severe carotid artery stenosis changes conventional
      risk factors, clinical picture of the disease and increases the risk of carotid
      endarterectomy.

PMID- 18326232
TI  - [Clinicoepidemiological features of echinococcosis in men serving in the navy].
AB  - AIM: To analyse echinococcosis morbidity and course characteristics in men
      serving in the Navy. MATERIAL AND METHODS: The results of annual 1983-2006 check
      up of Navy men were analysed to estimate echinococcosis morbidity in patients
      with eosinophilia and tumors including cysts. The diagnosis was made with
      application of clinical, ultrasound, radionuclide, morphological (including
      parasitological), biochemical and immunological methods, computed tomography.
      RESULTS: 14 cases of hydatid echinococcosis were documented. Most of the patients
      (85.7%) were young (18-22 years of age). The patients were infected before the
      army in highly endemic regions. Solitary echinococcosis was detected in 8
      patients. In multiple echinococcosis 1 patient had 4 cysts, 3 patients--3, 2
      patients had 2 cysts. Echinococcosis of stage 1 was diagnosed in 3 patients,
      stage 2--in 11 patients. All the patients had cysts in the liver. In multiple
      echinococcosis the cysts occurred more often in the liver, spleen, kidney; they
      were rare in the lungs, bones, brain. Pain, asthenovegetative, dyspeptic and
      allergic syndromes were registered in 71.4, 28.6, 14.3 and 7.1 cases,
      respectively. Eosinophilia was encountered in 42.9% cases. These syndromes were,
      as a rule, weakly pronounced. Before accurate diagnosis 6 patients for 4-10
      months were treated outpatiently for chronic gastroduodenitis, recurrent
      lumbalgia, biliary dyskinesia and intercostal neuralgia. CONCLUSION:
      Echinococcosis incidence rate in the Navy men is very low. They are infected
      before the army. The disease is diagnosed by chance or late, manifests primarily
      with pain symptoms.

PMID- 18326230
TI  - [Cholesterosis of the gall bladder and atherogenic dyslipidemia: etiology,
      pathogenesis, clinical symptoms, diagnosis and treatment].
AB  - AIM: To detect specific morphological signs of hepatic lesion in patients with
      cholesterosis of the gall bladder and atherogenic dyslipidemia in the presence of
      steatohepatitis. MATERIAL AND METHODS: Atherogenic dyslipidemia was detected in
      150 patients with steatohepatitis. Ultrasound investigation diagnosed
      cholesterosis of the gall bladder in 51.3% patients. The protocol included the
      following examinations: analysis of the disease history, physical examination,
      laboratory, device and morphological tests. Thirty patients received therapy with
      ursodesoxycholic acid medicine for 3 months. RESULTS: Basic clinical symptoms of
      gall bladder cholesterosis (GBC) and its risk factors are defined. The
      biochemical blood test registered elevated levels of transaminase, alkaline
      phosphatase and bilirubin. All the patients had an atherogenic type of
      dyslipidemia. According to USI, a focal-reticular form of GBC prevailed.
      Histologic examination of the liver detected the following alterations: fat
      infiltration, portal and intralobular infiltration, hydropic dystrophy, binuclear
      hepatocytes, lobular hepatitis, fibrosis of the portal tracts, periductular
      fibrosis, ductual proliferation, ductual epithelium detachment. Histologically,
      the walls of the gall bladder contain foam cells in the mucous and submucous
      layer. The same changes were seen in the wall of the hepatic artery as well as
      cholesterol polyps, epithelial destruction. Ursosan treatment resulted in a
      significant lowering of total cholesterol. CONCLUSION: GBC seems to be a chain of
      successive conditions: lipid disbolism at the level of hepatocyte, development of
      steatosis, steatohepatitis, fibrosis, involvement of all anatomo-morphological
      structures of the liver including the biliary tract, GBC.

PMID- 18326228
TI  - [The angiotensin II inhibition escape phenomenon in patients with type 2 diabetes
      and diabetic nephropathy].
AB  - AIM: To study prevalence and clinical implications of paradoxical rise of
      angiotensin II (AII) level in blood plasma in long-term therapy with ACE
      inhibitors in patients with type 2 diabetes mellitus (DM-2) and diabetic
      nephropathy (DN). MATERIAL AND METHODS: General clinical and hormonal (renin,
      AII, aldosteron, endothelin-1) examinations were conducted in 62 patients (37
      males and 25 females) with DM-2 and DN on long-term ACE inhibitors. Escape of AII
      inhibition was defined as an increase in plasma AII more than 50 pg/ml
      corresponding to M+1SD in the control group (normotensive persons free of DM
      matched by age). Diet salt was controlled in all the patients. RESULTS: The
      patients received ACE inhibitors for 7.8 +/- 2.6 years. Plasma AII level in the
      control group was 34.5 +/- 16.1 pg/mL. The patients were divided into two groups
      according to their levels of AII: more than 50 pg/ml (group 1), less than 50
      pg/ml (group 2). AII inhibition escape occurred in 24 patients (39%). No
      significant difference between the groups was registered by age, diabetes
      history, albuminuria, blood lipids, glycosylated hemoglobin, mean circadian blood
      pressure, duration of therapy with ACE inhibitors, intake of diuretics and beta
      blockers. Patients of group 1 had a significantly higher cardiac interventricular
      septum thickness (p = 0.02), were more likely to have akinetic segments of the
      myocardium (p = 0.05), had lower 24-h urinary potassium (p = 0.03),
      insignificantly higher renal insufficiency. Plasma renin concentration was higher
      in group 1 (p = 0.004). AII did not correlate with aldosterone levels in both
      groups. CONCLUSION: A relatively large percentage of type 2 diabetics with DN is
      due to AII inhibition escape. It may explain the lack of reno- and
      cardioprotective effect of rennin-angiotensin-aldosterone system blockade.

PMID- 18326229
TI  - [Urinary excretion of proinflammatory cytokines and transforming growth factor
      beta at early stages of diabetic nephropathy].
AB  - AIM: To examine correlations between urine excretion of proinflammatory
      cytokines, transforming growth factor beta (TGF-b) and changes in renal structure
      and function, quality of glycemia control in patients with type 1 diabetes
      mellitus. MATERIAL AND METHODS: Urinary excretion of interleukine 1-beta (IL-1b),
      monocytic chemoattractive protein-1 (MCP-1), RANTES and TGF-b was measured with
      enzyme immunoassay in 57 patients including 22 patients with normal albuminuria,
      23--with microalbuminuria, 12--with macroalbuminuria. Creatinine clearance was
      subnormal in 8 patients with macroalbuminuria. The control group consisted of 10
      healthy persons. Morphological examination of renal biopsies was performed in 8
      patients with normoalbuminuria and 10 patients with microalbuminuria. RESULTS:
      Patients with normoalbuminuria had excretion of MCP-1 significantly higher than
      in controls. Microalbuminuria patients showed high excretion of IL-1b, MCP-1 and
      TGF-b. Excretion of IL-1b, MCP-1, RANTES and TGF-b in patients with
      macroalbuminuria was higher than in controls and other groups of patients.
      Excretion of cytokines and TGFb correlated inversely with glomerular filtration
      rate and hemoglobin level. Positive correlations were detected between excretion
      of IL-1b, MCP-1, TGFb and glycated hemoglobin A(1c). In patients with normo- and
      microalbuminuria cytokine and TGFb excretion correlated with thickness of
      glomerular and glomerular basal membrane. CD68-positive macrophages were detected
      in the intersticium of 1 patient with normoalbuminuria and 6 patients with
      microalbuminuria. CONCLUSION: Urinary excretion of proinflammatory cytokines and
      TGF-b was elevated in patients with DM-1 having micro- and macroalbuminuria
      suggesting participation of inflammation in development of diabetic nephropathy.

PMID- 18326231
TI  - [Impaired expression of genes regulating homeostasis of stem hemopoietic cells in
      stromal cells of patients with aplastic anemia].
AB  - AIM: To evaluate expression of genes participating in regulation of hemopoietic
      stem cells (HSC) in the cells of stromal sublayer of bone marrow long-term
      cultures in patients with aplastic anemia (AA); to determine effects of
      parathyroid hormone (PTH) on stromal microenvironment and on its ability to
      maintain HSC homeostasis. MATERIAL AND METHODS: Gene expression in the sublayer
      of the adherent cells (SAC) was examined with RT-PCt. SAC was for a long time
      treated with PTH, then their ability to secure survival of early hemopoietic
      precursors was tested. Changes in the function of stromal cells and expression of
      some genes were compared in 9 AA patients and 14 donors. RESULTS: Stromal
      sublayer of AA patients is characterized by low expression of Ang-1 and VCAM-1
      genes and high VEGF expression compared to mean level of healthy donors. PTH
      stimulates expression of different genes participating in HSC regulation in
      stromal cells of some patients and improves survival of early hemopoietic
      hemopoietic precursors on such sublayers. CONCLUSION: AA patients have severe
      defects in SAC interaction with stroma. In some cases the defects can be
      partially compensated with application of PTH.

PMID- 18326233
TI  - [Prevalence of tobacco smoking among urban population of Samara and causative
      factors].
AB  - AIM: To examine prevalence and intensity of smoking among general population of
      Samara, physicians and students of Samara Medical University; to study dependence
      of this prevalence on different social factors. MATERIAL AND METHODS: A
      representative sample of adult population was selected by the lists of
      outpatients of Samara outpatient clinic. The study enrolled 2931 outpatients
      (1272 males, 1659 females aged 15 years and older)--3.95% of all Samara
      outpatients. The questionnaire survey covered 360 physicians aged 28-57 years
      (the response 96.5%), 652 senior medical students aged 21-24 years (the response
      93.14%). The results were processed with the statistical computer program
      BIOSTAT. RESULTS: The percentage of smoking men among 15-19-year-olds was 42.94%,
      20-29-year-olds--59.29% (p < 0.01), 30-39-year-olds--62.18%, 60-year-olds and
      older--35.64%. This proportion for smoking women was 15.04%, 27.11% (p < 0.01),
      22.92%, 9.06% (p < 0.001), 5.04%, respectively. Among male physicians smokers
      were 47.37% (14.29% smoked less than 10 cigarettes, 50.79%--10-20 cigarettes,
      34.92%--more than 20 cigarettes a day); 16.54% male physicians smoked earlier,
      36.09% never smoked. Relevant percentage for female physicians was 25.99 (38.98,
      47.46, 13.56, 13.66 and 60.35, respectively). Among male medical students smokers
      were 58.6% (29.2% less than 10 cigarettes a day, 55.8%--0-20, 14.9%--more than 20
      cigarettes a day); 9.1% smoked earlier, 32.3% never smoked. Among female medical
      students smokers were 20.3% (70.9, 21.5, 7.6, 9.3 and 70.4%, respectively).
      CONCLUSION: Tobacco smoking depends on education and marital status. Both in men
      and women the least number of smokers are among persons with higher education and
      married ones.

PMID- 18326234
TI  - [Renal affection in hypertensive patients with type 2 diabetes mellitus].

PMID- 18326235
TI  - [Genetic aspects of myocardial hypertrophy in hypertrophic cardiomyopathy and
      arterial hypertension].

PMID- 18326236
TI  - [Prognostic factors in multiple myeloma complicated with renal failure].

PMID- 18326237
TI  - [Results of ADVANCE trial conducted in type 2 diabetic patients].

PMID- 18326238
TI  - [Developing, state-of-the-art and prospects of forensic examination of gunshot
      trauma].

PMID- 18326239
TI  - [State-of-the-art of mathematical modeling of postmortal thermodynamics for the
      time of death determination].
AB  - Mathematical modeling of postmortal themperature used at present for definition
      of prescription of the death is shown in the article from a position of theory
      ofprobablibistic functions. Accuracy of examined techniquies is analized by
      comparison of modeled temperatures with real, fixed by the authors on a material
      of 158 expert supervisions. The conclusion about inadmissibility of practical use
      of some mathematical expressions is made in connection with low accuracy of the
      mathematical device used in them.

PMID- 18326240
TI  - [Forensic biological examination--the reality and perspectives].
AB  - The point of view of authors on the modern condition and priority directions of
      the development of examination of biological material evidence is set out. The
      main idea consists in the necessarily of reorganization and correction of
      organization methodical base of examination of biological material evidence. The
      role and place in examination of material evidence of traditional serological and
      new--molecule genetic components are determined in this direction. It is noted
      that forensic biology must not ever be associated with only one of its part-
      serological methods of analysis. Under growing influence of molecule genetic
      component the semantic, and methodical content of forensic examination of
      material evidence. This is not already auxiliary differentiation of examination
      objects but conclusive set of their equality or difference. Thus forensic
      biological department of forensic medical examination Office must become expert
      compartments of new type due for complex analysis of material evidence where
      molecule genetic technologies lie in the centre. All other methodical
      compartments of forensic biology also will be used but as auxiliary and
      additional methods. In perspective it is necessary to enlarge and centralize of
      high-tech forensic molecule genetic laboratories based on common science
      methodical approach. Unfavorable outcome of medical aid: study of the problem in
      forensic medicine practice

PMID- 18326241
TI  - [Characteristics of craniofacial identification using some comparative
      materials].
AB  - The peculiarities and techniques of craniofacial identification using lifetime
      video and X-ray photographs presented as comparative materials are examined.

PMID- 18326242
TI  - [State-of-the-art of forensic examination of material evidence].

PMID- 18326243
TI  - [Forensic stomatology as independent division of forensic medicine].
AB  - A modern condition of identification with use of stomatological state is set out
      in details. Dissertations of research assistants and competitors of the
      department of forensic medicine were analyzed in connect with the problem of
      identification using anatomy, morphological and morphometrical peculiarities of
      tooth, dental arches, dental plates, oral cavity organs and others. A possibility
      of identification of sex, age, ethno-racial affiliation using peculiarities of
      structure of dental-jaw system was presented. A question connected with coverage
      of this problem in pages of "Forensic examination".

PMID- 18326244
TI  - [To the evaluation of work of the department of complex commission examinations].

PMID- 18326245
TI  - [Unfavorable outcome of medical service: study of the problem in forensic
      medicine].
AB  - The main tendencies in the development and study of the problem of unfavorable
      outcome and expert assessment of quality of medical aid were examined. Russian
      and foreign forensic medicine and juristic practice were compared. A combined
      approach to improve of forensic medical expertise and to prevent delinquencies of
      medical stuff was proposed.

PMID- 18326246
TI  - [The stages of improvement of forensic examination in sex crimes and arguable sex
      conditions according to the materials of the magazine "Forensic Examination"].

PMID- 18326247
TI  - [The history of periodical press on the matter of forensic medicine in Russia].

PMID- 18326248
TI  - [Forensic evaluation of the time since rib fractures].
AB  - Visual, stereomicroscopic and histological analysis of 216 fractures of ribs
      extracted from 83 dead bodies was carried out during forensic examination in
      cases of blunt trauma of chest in 58 male and 25 female. It was revealed that
      modifications of rib fragments, determined with fractometrical method in the zone
      of contact (trasses, rubbings, polishings) can be used for forensic diagnostic of
      prescription of ribs fractures. There were revealed characteristic properties of
      sphacelous, inflammatory and regenerative processes in the zone of ribs fractures
      which consist in the fact that hemolysis of red blood cells, leucocyte and
      macrophagal reaction, sphacelous modifications of tissues, formation of
      granulation tissue are developing faster and proliferation of fibroblasts becomes
      later than in impairments of other localizations and types. The complex use
      offractometrical and histological methods increase accuracy and objectiveness
      offorensic diagnostic of prescription of mechanical trauma of chest.

PMID- 18326249
TI  - [Biomechanism of intracranial and spinal trauma of child born in occipitoanterior
      presentation as used in forensic examination].
AB  - The new conception of mechanism and sequence of damages typical for labor trauma
      is presented: injury of ligaments of atlas and axis and anterior atlanto
      occipital membrane, ruptures of synchondrosises of cranial bones because of
      vertebral column pressing on occipital bone; tears of dura mater of brain upon
      basilar impression in the area of focal spot; subarachnoid hemorrhage and
      intracerebral bleeding in case of cerebral compression by bone borders where they
      overly override; ruptures of ligaments of cervico-occipital and intervertebral
      joints in case of excess flexion and overextension of head. Authors show that
      damage of sutures, bones of calvarium and partition parts of dura materialize
      later than injury of synchondrosises of base and they are absent if
      sinchondrosises are not damaged. Also iatrogenic damages of fetal in labor and
      the mechanism of their formation are described.

PMID- 18326250
TI  - [Hemodynamics, the autonomic nervous system and water metabolism as criteria for
      developing the general adaptation syndrome in pregnant women].
AB  - By taking into account the fact that the autonomic nervous and cardiovascular
      systems (ANS and CVS) are the major links of development of the general
      adaptation syndrome in pregnancy, which are affected by all the processes
      involved in the development of the syndrome, the author analyzed the state of
      these systems in healthy non-pregnant and pregnant women (HNPW and HPW) and in
      pregnant women with gestosis. HNPW were found to have already a prerequisite for
      impairing pregnancy adaptive processes as ANS and CVS dysfunction. In HPW, these
      impairments were more pronounced. In the pregnant women, impaired adaptive
      processes manifested themselves as excess sympathicotonia in 72% and
      parasympathicotonia in 23% of cases despite the treatment performed, which was
      accompanied by hypokinetic hemodynamics in 53 and 50%, respectively. In hyper-
      and eukinetic hemodynamics, there were no physiologically required decreases in
      total peripheral vascular resistance while in hypokinetic hemodynamics, there was
      its pathological increase. Such disorders enhance the significance of abdominal
      compartment syndrome, aortocaval compression, ischemia-reperfusion, hydrodynamic
      and membranogenic (capillary leakage) factors of impaired water metabolism, which
      contributes to adaptation derangement. Based on the findings, the authors have
      created a developmental modulation algorithm for the general adaptation syndrome
      by completed pregnancy and surgical delivery.

PMID- 18326251
TI  - [Transient neurological symptoms in puerperas after epidural analgesia during
      labor].
AB  - The investigation was undertaken to elucidate the impact of epidural analgesia
      (EA) during labor on the incidence of transient neurological symptoms (TNS). By
      the agreement of a local ethics committee, an informed consent was obtained from
      90 healthy puerperas enrolled in the investigation. The patients were randomized
      into 3 groups, with 30 patients in each. At the beginning of labor, an epidural
      catheter was inserted in all the puerperas. For EA, 1% lidocaine solution and
      0.2% ropivacaine solution were used in Groups 1 and 2, respectively; Group 3 was
      control in which EA was not performed. Two days after labor, an independent
      observer asked the females about possible neurological symptoms, by using the
      standard questionnaire. TNS included symmetric pain and/or dysesthesia in the
      buttocks, lower lumbar region, and/or legs. The patients who presented problems
      were proposed to indicate the degree of discomfort by a 10-score verbal scale.
      The findings were statistically processed using the U-test and X-test (p < 0.
      05). A total of TNS occurred in 22 (25%) patients, including 7 (27%), 8 (27%),
      and 7 (23%) in Groups 1, 2, and 3, respectively. This difference was not
      statistically significant. The duration of TNS was generally short; in all the
      patients, the symptoms were completely resolved after 24-72 hours. Labor EA is
      not a cause of TNS. The type of a local anesthetic (lidocaine, ropivacaine) does
      not affect the incidence of TNS in puerperas after labor EA.

PMID- 18326252
TI  - [Optimization of anesthetic service during abdominal delivery of pregnant women
      with gestosis].
AB  - Differential preoperative preparation of pregnant women with gestosis, by using
      calcium antagonists is an effective preventive measure against a circulatory
      hyperdynamic response to transportation to the operating suite. In pregnant women
      who had all hemodynamic types at baseline, the eukinetic type achieved during the
      preparation is retained. The patients with gestosis who did not receive calcium
      antagonists were found to have a circulatory hyperdynamic response with increased
      myocardial oxygen uptake (during surgery in particular). The use of calcium
      antagonists, ketonal, tranexamic acid, and hydroxyethyl starch-130/04 solution in
      the anesthetic appliance promoted the preservation of eukinetic hemodynamics in
      all those operated on, without increasing myocardial oxygen demands. The better
      reaction of the circulatory system and myocardial oxygen demands to surgical
      injury (the second mediatory wave of the systemic inflammatory response syndrome)
      correlated with higher neonatal Apgar scores in this category of puerperas with
      gestosis.

PMID- 18326253
TI  - [Risks of surgery and anesthesia and optimization of anesthesiological
      maintenance of abdominal delivery].
AB  - The paper deals with abdominal labor pain relief in pregnant women at high risk
      for impaired development of the general adaptation syndrome: significant
      sympathicotonia, placental ischemia-reperfusion syndrome, and systemic
      inflammatory response syndrome. All these syndromes are attended by either
      impaired oxygen transport or a high risk for the occurrence of such at surgery.
      The detection and correction of these impairments in development of the general
      adaptation syndrome in pregnancy, which are provided by the author's modified
      rating scale for risks of surgery and anesthesia, contribute to the development
      of the body's compensated metabolic reaction to surgical injury, reducing the
      number of maternal, fetal, and neonatal complications.

PMID- 18326254
TI  - [Subarachnoidal anesthesia during emergency abdominal delivery].

PMID- 18326255
TI  - [Hemodynamics in puerparas during subarachnoidal anesthesia with lidocaine].
AB  - Hemodynamic changes in response to subarachnoidal injection of 1.2-1.4 mg/kg of
      lidocaine at various concentrations were comparatively evaluated in 106 pregnant
      women aged 21 to 36 years (with 53 patients in each group). All the women
      underwent lumbar puncture at the level of L(II)-L(IV), 1.2-1.4 mg/kg of
      hyperbaric lidocaine solution being subarachnoidally administered. Groups 1 and 2
      patients received 2 and 5% solution of the anesthetic, respectively. At the
      stages of anesthesia and surgery, the investigators examined central
      hemodynamics, recorded the duration of a complete segmental sensomotor block and
      the number of blocked segments (the extent of block). No significant differences
      were established at the time of development of a complete sensomotor block with
      the use of 2% (Group 1) and 5% (Group 2) lidocaine solutions. At the same time
      there were 16.8 +/- 0.6 and 11.9 +/- 0.5 blocked segments in Groups 1 and 2,
      respectively. In Group 1, severe hemodynamic disorders to be corrected were
      recorded in 30.2% of the women and in Group 2, subarachnoidal administration of
      the same doses of lidocaine did not cause any disorders.

PMID- 18326256
TI  - [Anesthetic risk factors during spinal anesthesia in obstetrics].

PMID- 18326257
TI  - [Anesthetic service and the postoperative period in pregnant women with
      gestosis].
AB  - The paper analyzes the results of using in the anesthetic maintenance of pregnant
      females with gestosis the algorithm of preventing possible impairments in the
      development of the general adaptation syndrome in response to pregnancy and
      surgical labor. Calcium antagonists (eliminating dysfunction of secondary calcium
      messenger), ketonal, and tranexamic acid (which inhibiting a number of pain and
      inflammation mediators), and hydroxyethyl starch-130/04 solution (regenerating
      the endothelium) were administered to prevent the clinical manifestations of the
      intraabdominal compartment syndrome, ischemia-pefusion, and the second wave of
      the systemic inflammatory response syndrome in response to surgery. The
      differential use of the above agents at all stages of anesthetic maintenance in
      pregnant women with gestosis promoted the postoperative preservation of the most
      efficient eukinetic hemodynamics and physiological sympathicotonia and the
      elimination of water metabolic disturbances more early than in the control
      puerperas. A more physiological postoperative course in the study group puerperas
      called for much less pharmacotherapy, which created more favorable conditions for
      postoperative maternal-neonatal contact (feeding, etc.).

PMID- 18326258
TI  - [Hemostatic therapy for hemorrhages during first and second trimesters].
AB  - Hemorrhages during pregnancy are the conditions requiring emergency therapy. The
      aim of the investigation was to study the efficiency of tranexamic acid (the drug
      Tranexam) in arresting bleeding and prolonging pregnancies in women with a
      history of threatened abortion and miscarriage. In the group of women taking
      tranexamic acid as part of pathogenetic treatment, hemostasis occurred more
      rapidly than in the control group and hence uterine hematomas resolved on shorter
      notice. Inclusion of tranexamic acid into the treatment regimen for patients with
      threatened and incipient abortion is effective in rapidly arresting hemorrhage
      and prolonging pregnancy.

PMID- 18326259
TI  - [Current technologies for blood loss prevention during abdominal hysterectomy].
AB  - The paper deals with the development and use of original adequate transfusion
      infusion programs to compensate for blood loss in abdominal hysterectomies for
      uterine myomas of varying sizes, by applying the current blood-supplying
      technologies that permit avoidance of transfusion of donor blood components. Four
      blood loss-replenishing programs in abdominal hysterectomy for large-sized myomas
      were studied for impact on the basic functions in premenopasal women. These
      included: (1) preoperative blood storage of blood autocomponents; (2)
      normovolemic hemodilution with hydroxyethyl starch (HES) solution being used as a
      dilutant; (3) administration of HES solutions as an independent solution
      compensating for blood loss, and (4) intraoperative reinfusion of
      autoerythrocytes. The proposed transfusion-infusion programs in abdominal
      hysterectomy for large-sized myomas by applying blood-preserving methods are
      effective in avoiding the use of donor blood components and accordingly in
      reducing the frequency of complications associated with transfusions of donor
      blood components, and improving the postoperative period.

PMID- 18326260
TI  - [Current approaches to correcting blood loss in obstetric care].
AB  - The paper considers current approaches to the strategy and tactics of infusion
      transfusion therapy (ITT) in the development of obstetric bleedings. The results
      of treatment were analyzed in 124 patients in whom pregnancy or labor had been
      complicated by hemorrhage. Various ITT options are presented depending on the
      volume of blood loss and physiological background. The ITT programs applied are
      based on the combined used of colloid and crystalloid solutions and hypertonic
      sodium chloride solution. With increased blood loss volume, artificial colloids
      are gradually excluded from an ITT program in the following order: dextrans,
      hydroxyethyl starch, and gelatin derivatives. Subsequently, priority is given to
      natural colloids. Blood components were transfused if strictly indicated. The
      studies have indicated that the baseline blood circulation of patients with
      physiological and severe gestosis-complicated pregnancy should be taken into
      account during ITT for acute obstetric blood loss. The differential approach to
      ITT and its pattern and type depend on the quantity of lost blood, that should be
      calculated as percentage with reference to the volume of circulating blood of a
      pregnant woman rather than relied on its total volume. The pathophysiologically
      substantiated approach to ITT for acute obstetric blood loss with the
      physiological background being kept in mind makes it possible to stabilize the
      parameters of blood circulation, volemic and colloid-osmotic homeostasis, thereby
      reducing the incidence of postoperative complications.

PMID- 18326261
TI  - [Role of mobile intensive care team in reducing maternal mortality in Moscow].
AB  - As of now, exit intensive care teams (EICT) are a mobile service of the S. P.
      Botkin City Clinical Hospital. The main area of their activity is to deliver
      intensive care to 35 Moscow obstetric hospitals. In 2003-2006, the EICT mates
      performed 1159 calls, delivered care to 783 puerperas and parturiants, and
      transferred patients to the specialized intensive care units and research centers
      of Moscow. Throughout the existence of the exit intensive care center and EICT,
      none patient died during interhospital transportation. The concentration of these
      patients at 4 specialized Moscow hospitals could improve a therapeutic process,
      gain uniqe clinical experience, and reduce mortality by 3-fold (from 45.2 to
      14.6%).

PMID- 18326262
TI  - [Emergency abdominal delivery and ventriculoperitoneal bypass in pregnant females
      with brain tumor].
AB  - The paper describes a case from the practice of the maternity hospital, City
      Hospital Sixty-Seven. The pregnant woman at gestational weeks 36-37 was found to
      have a brain tumor complicated by obstructive hydrocephalus and dislocation
      syndrome. Ventriculoperitoneal bypass and abdominal delivery were simultaneously
      performed under endotracheal anesthesia using propofol, nitrous oxide, and small
      dose ketamine (25 mg), and after fetal extraction, fentanyl. At minutes 1 and 5,
      the Apgar score of the neonate was 8 and 8, respectively. The patient was
      discharged from the hospital in satisfactory condition on day 7 postoperatively
      and it was recommended that her surgical treatment at a neurosurgical clinic be
      decided.

PMID- 18326263
TI  - [Ovarian overstimulation syndrome: problem of intensive care].
AB  - Ovarian hyperstimulation syndrome (OHSS) is an iatrogenic complication, the basis
      for which is a hyperergic uncontrolled ovarian response to gonadotropins in the
      ovulation stimulation cycles and assisted procreation programs. The clinical
      picture of OHSS is characterized by a broad spectrum of clinical and laboratory
      manifestations: increased vascular permeability resulting in the excess release
      of liquid into the third space and its storage with the development of
      hypovolemia, hemoconcentration, oliguria, hypoproteinemia, electrolyte imbalance,
      polyserositis; in severe cases, acute renal failure, thromboembolic events, and
      adult respiratory distress syndrome develop. The goal of treatment is to prevent
      the development of multiply organ dysfunctions. Its leading methods are infusion
      therapy with colloid-crystalloid solutions and anticoagulant therapy. Whether
      diuretics and other drugs are administered is under consideration. Indications
      for laparocentesis and peritoneal transudate evacuation are discussed.
      Complications requiring surgery are identified.

PMID- 18326264
TI  - [Prospects for using combined spinal-epidural anesthesia in obstetric care].

PMID- 18326265
TI  - [Antithrombin III in the treatment of sepsis-- new approaches to prescribing the
      old drug].

PMID- 18326266
TI  - [Optimization of anesthetic maintenance of a facial dermabrasion operation].
AB  - Facial dermabrasion requires the preservation of natural mimic muscle tone,
      adequate spontaneous respiration, and contact with a patient. By taking into
      account the commercial pattern of surgical interventions, anesthesia should be as
      safe and comfortable as possible. For these purposes, the standard procedure of
      intravenous anesthesia with spontaneous respiration being preserved is optimized
      on the anticipatory analgesia principle, by using analgesics having the non
      opiate mechanism of action: the kininogenesis inhibitor transamine and the
      nonsteroidal anti-inflammatory drug ketonal. This makes it possible to provide
      the adequacy of anesthesia and a good cardiovascular response with the doses of
      narcotic analgesics, hypnotics, and an anxiolytics, which do not cause
      respiratory distress, and to avoid using narcotic analgesics. The use of the
      antiemetics tropisetron and dexamethasone at the induction stage of anesthesia
      has been ascertained to be a reliable preventive measure against postoperative
      nausea and vomiting, by substantially enhancing its comfortability.

PMID- 18326267
TI  - [National "Health" project--role of industrial medicine].

PMID- 18326268
TI  - [Measures complex to preserve health of medical professionals working with modern
      hi-tech equipment].
AB  - The authors defined major directions of measures complex to preserve health of
      medical professionals working with modern hi-tech equipment. Special attention is
      focused on sanitary and epidemiologic examination of medical equipment to create
      safe work conditions for maintenance staff.

PMID- 18326269
TI  - [Safety problems of modern laser medical equipment].
AB  - The authors consider topics connected with improvement of hygienic regulation of
      laser radiation, define most important problems associated with safety of modern
      laser medical devices.

PMID- 18326270
TI  - [Comparative evaluation of health state in workers of metal mining industry].
AB  - The article covers up-to-date state of work conditions, occupational and general
      morbidity in workers of metal mining enterprises situated in contrast climate
      regions of Russian Federation. The authors revealed peculiarities of functional
      state in metal mining workers of Arctic and European Russia.

PMID- 18326271
TI  - [Retrospective analysis and prognosis of lung cancer morbidity in Kouzbass].
AB  - The authors present results of retrospective analysis of lung cancer morbidity in
      Kouzbass from 1990 to 2005. The morbidity parameters appeared to depend on
      volumes of coal mining and treatment. Prognosis of lung cancer incidence was
      calculated up to 2014 with consideration of actual volumes of coal mining and
      treatment.

PMID- 18326272
TI  - [Topical problems of occupational deafness].
AB  - The article covers up-to-date state of occupational deafness problem, its
      importance in occupational therapy. The authors defined topical directions of
      research in contemporary diagnosis, prognosis and treatment of "noise-related"
      deafness.

PMID- 18326273
TI  - [On efficiency of local xidiphone in treating osteoporotic changes in hands of
      vibration disease patients].
AB  - The authors demonstrated that local electrophoresis of xidiphone for osteoporotic
      changes in hands of vibration disease patients results in preservation of bone
      mineral density. Treatment courses should occur 2-3-4 times annually.

PMID- 18326274
TI  - [Influence of asbestos dust combination with radiation on activity of enzymes
      involved into purine nucleotides metabolism in various tissues and organs].

PMID- 18326275
TI  - [The theory of functional systems and clinical medicine].
AB  - The clinical significance of Anokhin's theory of functional systems is analyzed.
      The concept of a useful result as a universal system-forming factor is debatable.
      This concept limits the application of the theory to only compensatory-adaptive
      reactions and, what is more, makes the theory contradictory (the primary
      achievement of a result usually occurs due to the activity of an already formed
      system, which excludes its system-forming role). The article substantiates the
      existence of several system-forming factors as well as the ability of each of
      them to form physiological, pathological, and ambivalent systems. When taken into
      account, these concepts eliminate contradictions of the theory and widen the area
      of its practical application.

PMID- 18326276
TI  - [Solar activity and cardiovascular diseases].
AB  - Many-year research into biological effects caused by solar activity has proved
      that the response of biological objects, including human organism, to
      heliogeomagnetic disturbances presents an adaptive stress reaction. This response
      can be irreversible only in organisms whose adaptive system works improperly due
      to a pathological condition or overstress. Studies dedicated to the role of
      melatonin--an epiphysial hormone--in human and animal stress protection, are of
      interest. The application of physiological doses of melatonin as an anti-stress
      agent is based on its adaptogenic effects and its role as an endogenous
      biological rhythm synchronizer.

PMID- 18326277
TI  - [Hemorrhage from esophageal varices].
AB  - The lecture deals with the ethiology and pathogenesis of portal hypertension
      (PH). Three variants of PH are distinguished. Endoscopic signs of PH and
      esophageal varicosis are described. The clinical picture of hemorrhage from the
      esophageal varices veins (EP) and kinds of pharmaceutical, endoscopic, and urgent
      surgical aid are described. Primary and secondary prophylaxis of hemorrhage from
      EV is covered.

PMID- 18326278
TI  - [Factors associated with cardiac arrhythmias in patients with type 2 diabetes
      mellitus and myocardial infarction].
AB  - An analysis of some features of heart arrhythmias in patients with myocardial
      infarction (MI) and type 2 diabetes mellitus (DM2) was performed. The study
      revealed that arrhythmias (usually extrasystoles or atrial fibrillation) were
      more common in patients with DM type 2 (42.1% in DM2, and 30.4% in non-DM
      patients, p = 0.0041) and demonstrated a direct correlation with coronary and
      myocardial dysfunction. In patients with DM2, arrhythmias were associated with
      the duration of DM and HbA1c level. In severe metabolic decompensation (HbA1c >
      8.5%) and in cases with a relatively low HbA1c level (< 7%) arrhythmias were more
      frequent than in patients with an HbA1c level between 7.0% and 8.5%. In patients
      with an HbA1c level < 7.0%, the threat of hypoglycemia is increased, often due to
      insulinotherapy, as a possible arrhythmogenic factor associated with a relative
      elevation of immunoreactive insulin and C-peptide and diabetic nephropathy (DN).
      Severe DM decompensation (HbA1c > 8.5%) was associated with metabolic
      disturbances and toxic effect of hyperglycemia. Cardiac arrhythmias, systolic
      dysfunction, and DN are prognostically unfavorable factors influencing the
      survival rate in patients with MI and DM2.

PMID- 18326279
TI  - [Inflammatory reactions in patients suffering from coronary artery disease with
      concomitant obesity and type 2 diabetes mellitus].
AB  - Of late, inflammatory reactions have been considered to play an important part in
      the development of atherosclerosis. Acute-phase inflammatory reaction, being
      initially a protective response directed within the homeostasis system towards
      lesion repair, may by itself due to various factors favor the development of
      pathological processes. Considering the role played by inflammation in the
      development of atherosclerosis, and inflammatory activity in obesity and diabetes
      mellitus (DM), a range of common and interrelated elements of these processes may
      be marked out. These are acute phase proteins and cytokines. Insulinoresistance,
      being the common precursor of obesity and DM, plays the key role in vascular
      lesion. The use of cytokine activity index seems to be a promising method of
      revealing patients with high risk of atherosclerosis.

PMID- 18326280
TI  - [The influence of depression on the aggregate state of blood in elderly patients
      with cardiovascular diseases].
AB  - The work is dedicated to the effects of the psychoemotional status of patients
      older than 65 suffering from coronary artery disease (CAD) and arterial
      hypertension (AH) on the aggregative status of blood. Sixty-eight patients with
      mild stable stenocardia accompanied by AH and comorbid depression (CD) were
      examined; 28 elderly patients with CAD, AH, and no CD constituted the comparison
      group. The study found that CD in elderly patients with stable stenocardia did
      not only lower the quality of life, but also worsened hemodynamic parameters. CD
      increases hypercoagulatory shift, inhibits the fibrinolytic system of blood, and
      elevates the risk of thrombus formation.

PMID- 18326281
TI  - [Cardiac rhythm variability during active orthostatic test in patients with
      arterial hypertension].
AB  - The aim of the study was to evaluate cardiac rhythm variability (CRV) during
      active orthostatic test (AOT) in patients with arterial hypertension (AH) living
      in Tyumen near-Ob region. Fifty-two patients with AH and 32 practically healthy
      persons were examined. Under outpatient conditions in the city of Pyt-Yakh, 5-min
      CRV recording was performed by standard technique in the supine position and
      during AOT, and temporary and spectral parameters were evaluated. In both groups,
      parameters of the temporary analysis of CRV during AOT differed significantly.
      The values of optimal variability in AH patients displayed significant
      deviations, while the deviations in the control group were moderate. Analysis of
      spectral parameters of CRV during AOT revealed an increase in the values of total
      spectrum power of CRV in both groups. The values of optimal CRV parameters
      evidenced the presence of disbalance in the vegetative regulation of cardiac
      rhythm in the subjects. The results of temporary analysis found a lowered
      activity of parasympathetic vegetative regulation, while spectral analysis
      revealed an increased sympathetic influence on cardiac rhythm. The values of the
      index of regulatory system tension during AOT suggest that in both groups the
      adaptive abilities of the mechanisms of vegetative regulation of cardiac rhythm
      were preserved.

PMID- 18326282
TI  - [Losartan for the correction of thrombocyte activity in patients suffering from
      arterial hypertension with metabolic syndrome].
AB  - The aim of the study was to evaluate therapeutic effects of losartan on
      intravascular thrombocyte activity (ITA) in patients suffering from arterial
      hypertension with metabolic syndrome (MS). The subjects of the study were 35
      patients administered losartan 50 mg a day for 4 months. The dynamics of the
      following parameters were evaluated: anthropometric parameters, blood lipids,
      lipid peroxidation in blood plasma and thrombocytes, the anti-oxidative
      protection of the liquid part of blood and platelets, and ITA. Student criterion
      was used for statistical analysis. In patients with AH and MS losartan had a
      positive effect on peroxidation syndrome and optimized ITA. To maintain the
      positive effects, prolonged administration of losartan is needed. In order to
      lower body mass in AH patients with MS losartan should be used in combination
      with non-drug means.

PMID- 18326283
TI  - [Activity index in rheumatic polymyalgias].
AB  - OBJECTIVE: The activity of rheumatic polymyalgia (RP) was assessed using
      simplified activity index (RPAI). MATERIAL AND METHODS: 76 patients with a valid
      diagnosis of RP were treated in the Rheumatological Department of the Territorial
      Clinical Hospital #1; the clinical picture of the disease and its activity were
      evaluated according to RPAI, and the effect of glucocorticoids (GC) on the index
      was assessed. RESULTS: All the subjects had a high RPAI at admission (32.8 +/-
      0.8). After three weeks of GC therapy RPAI decreased significantly. The frequency
      of RP recurrence correlated with the absence of remission after lowering
      prednisolone dose. CONCLUSION: Knowing the clinical manifestations and course of
      RP, the diagnosis is not difficult. However, for adequate treatment of patients
      the degree of disease activity needs to be assessed during monitoring, after dose
      lowering, and after prednisolone is discontinued.

PMID- 18326284
TI  - [The vegetative status in patients with vertebrogenic vertebral artery syndrome,
      and its correction with health resort treatment].
AB  - According to statistics, osteochondrosis is one of the most prevalent diseases
      resulting in changes in the musculoskeletal, nervous, and cardiovascular systems.
      In vertebral artery syndrome, the irritation of sympathetic plexuses around this
      artery results in vasomotor changes in the vertebrobasilar system and determines
      the clinical picture of the syndrome, i.e. its vegetalgic and angiodystonic
      components. Pathology of central regulatory mechanisms and suprasegmental
      divisions of the vegetative nervous system appears.

PMID- 18326285
TI  - [Outpatient diagnostics of the initial stage of essential hypertension].
AB  - The informative value of functional diagnostic methods in the revealing of the
      initial stage of essential hypertension (EH) in patients with high risk of
      cardiovascular complications (CVC) and type 2 diabetes mellitus (DM2) was
      studied. The subjects of the study were 186 men considering themselves
      practically healthy, with high risk of CVC according to SCORE scale. Mean age of
      the subjects was 47.9 +/- 0.87 years; persons with various metabolic disorders
      prevailed. The patients were divided into two groups according to body mass index
      (BMI): group 1 patients (n = 142) had a BMI of > or = 25 kg/m2 (29.16 +/- 0.49);
      group 2 (n = 46) patients had a BMI of < 25 kg/m2 (22.95 +/- 0.37). The patients
      underwent clinical and laboratory examination including the measurement of
      biochemical parameters of lipid, carbohydrate, and purine metabolism. ECG,
      EchoCG, and 24-hour blood pressure monitoring (BPM) were performed. Office BP
      levels, 24-hour BMP data, and signs of left ventricular hypertrophy (LVH)
      according to ECG and EchoCG were evaluated. The study found that in persons with
      excessive body weight stable 24-hour arterial hypertension with both systolic and
      diastolic BP increased prevailed, while in subjects with normal body weight
      systolic arterial hypertension prevailed. The use of milder LVH criteria (left
      ventricular myocardial mass index > 116 g/m2) increased the number of persons
      with stage 2 EH. The prevalence of the initial stage of EH according to 24-hour
      BPM (87.4%) is 2.8 times higher than that according to office BP measurement
      (31.3%).

PMID- 18326286
TI  - [Enteral nutrition in the complex treatment of patients with mechanical jaundice
      in gallstone disease].
AB  - The article summarizes the results of the examination and treatment of 99
      patients with mechanical jaundice (MJ) related to gallstone disease (GSD). The
      patients were distributed into three groups according to three degrees of the
      dysfunction of the greater duodenal papilla (GDP) sphincter. Group 1 consisted of
      52 patients with transitory MJ (degree I), Group 2 consisted of 32 patients with
      stable MJ remaining after coping with the pain attack (degree II), and Group 3
      consisted of 15 patients with MJ and cholangitis (degree III). Trophic status
      disturbances and the effects of balanced clinical nutrition on the results of
      surgical treatment were assessed in all the patients. The severity and duration
      of jaundice were found to influence the severity of trophic changes. Clinical
      nutrition (sipping and enteral tube feeding) favored survival after papilla
      sparing surgery in patients with MJ related to gallstone disease.

PMID- 18326287
TI  - [Physical work ability in patients with type 1 diabetes].
AB  - Physical work ability was assessed in 128 patients with a long duration of type 1
      diabetes mellitus and 36 practically healthy people by K. Wasserman stepwise
      standard loading test with permanent monitoring of the load, oxygen consumption,
      and respiratory coefficient. Oxygen consumption was calculated per 1 kg body
      mass, and anaerobic metabolism threshold was determined. The patients were
      divided into three groups: Group 1 consisting of patients without clinically
      detectable microangiopathic complications, Group 2 with initial, and Group 3 with
      advanced manifestations of late diabetic syndrome. Average levels of maximum
      oxygen consumption, the achieved load, oxygen consumption per 1 kg body mass at
      the peak of physical load, and anaerobic threshold were significantly lower in
      all the three groups compared to controls. Respiratory coefficient at the peak of
      loading testing was significantly higher in diabetic patients than in controls.
      The study demonstrated that microangiopathic alterations significantly reduced
      physical work ability in patients with type 1 diabetes mellitus. Nevertheless,
      this study demonstrated low physical exercise tolerance in a large part of young
      diabetics without clinically detectable microvascular complications of
      endocrinopathy. A decrease in maximum oxygen consumption in these patients may be
      of multi-factor nature and may be a result of both central (hemodynamics) and
      peripheral (microcirculation, muscular metabolism) mechanisms limiting the
      function of the gas transport system.

PMID- 18326288
TI  - [Differential diagnostics of acute inflammatory diseases and tumors of the neck].
AB  - The purpose of the investigation was to assess the clinical significance of
      ultrasonography for differential diagnostics between acute inflammatory and
      tumorous lesions of the neck. One hundred and eighty-six patients with soft
      tissue lesions of the neck aged 18 to 74 (mean age 31.45 +/- 8.39 years), 95
      (51%) males and 91 (49%) females were examined. Basing on clinical and
      ultrasonographic examination, the patients were divided into two groups: 149 or
      80% patients with acute inflammatory lesions (Group 1), and 37 or 20% patients
      with tumorous lesions (Group 2). Thirty-four of the 149 Group 1 patients (22.82%)
      had lymphadenitis, 30 (20.13%) had soft tissue infiltrates, 13 (8.72%) had
      abscesses, 19 (12.72%) had phlegmons, 32 (21.48%) had acute inflammatory changes
      in the major salivary glands, 3 (2.01%) had teratomas with signs of inflammation,
      and 17 (11.41%) patients had inflammatory changes in the tumors. Of 37 patients
      with tumorous lesions, 16 (43.2%) had salivary gland tumors, 12 (32.4%) had
      metastases in the lymphatic nodes, and 9 (24.3%) had neurofibromatosis. Soft
      tissue ultrasonography was performed using Sonos-5500 and Image-Point ultrasound
      scanners with 7.5 MHz sensors (Hewlett-Packard, USA), Logio-pro, Uoluson-730
      Expert (General Electric, USA), and Premium Edition (ACUSON Antares, Siemens,
      Germany) with 5 to 13 MHz wide-frequency sensors. Visualization was performed in
      B-modes using tissue harmonics, color duplex scanning, Sie Scape panoramic
      visualization, contrast visualization and Sight 4D and 3D-Scape modes. The
      results of ultrasonography were analyzed taking into account additional methods
      such as computed and magnetic resonance tomography, intraoperative findings, the
      results of puncture biopsy, histological, morphological, and bacteriological
      studies. The study demonstrates that ultrasonography is the method of choice,
      which is in some cases enough to establish a diagnosis of an acute inflammatory
      disease or a tumorous formation of various localizations in the neck.

PMID- 18326289
TI  - [Optimization of antihypertensive therapy in pregnant women using 24-hour
      arterial pressure monitoring].
AB  - The purpose of the investigation was to study peculiarities in the parameters of
      24-hour arterial pressure monitoring (APM) in pregnant women with various
      extragenital and obstetric pathologies to define indications to administration
      and optimization of hypotensive therapy. The results of 24-hour APM of 558
      pregnant women with a suspected arterial hypertension (AH) of different origins
      were matched with peculiarities of pregnancy and its outcome (gestosis, an
      abortion due to AH complications, serious obstetric complications such as
      intrauterine fetal death or detachment of placenta). The control group consisted
      of 41 women without cardiovascular diseases or any complications during
      pregnancy. The analysis of the results made it possible to offer a classification
      of 24-hour curves of systolic and diastolic arterial pressure and heart rate
      based on relations between these parameters. This classification is convenient
      for clinical application and makes it possible not only to define indications to
      hypotensive therapy, but also to recommend certain pharmacological group of
      hypotensive preparations in each particular case. Prognostication of the
      development of severe gestosis or serious obstetric complications.

PMID- 18326290
TI  - [A case of an effective application of probiotics in the complex therapy of
      severe type 1 diabetes mellitus and intestinal disbacteriosis].
AB  - The article presents a case illustrating an association between the severity of
      type 1 diabetes mellitus and disorder in the intestinal microbiocenosis. The
      authors stress that clinical signs of disbacteriosis are mostly manifested by
      disturbances in the metabolic processes. Clinical effectiveness of
      probioticotherapy in the complex treatment of the disease is shown.

PMID- 18326291
TI  - [The assessment of medical education and professional competence of a doctor].

PMID- 18326292
TI  - [Is spindle formation in fission yeast specific to the species?: from the
      viewpoint of nuclear transport and spindle pole body].

PMID- 18326293
TI  - [Molecular mechanisms for meiotic arrest that is cancelled by fertilization in
      vertebrate eggs].

PMID- 18326294
TI  - [Structure and function of prostaglandin D synthase].

PMID- 18326295
TI  - [Medaka draft genome].

PMID- 18326296
TI  - [Toxic conformer of the polyglutamine protein].

PMID- 18326297
TI  - [Structural basis for the mechanism of Mg2 homeostasis by MgtE transporter].

PMID- 18326298
TI  - [Proline functions and its metabolic regulations in yeast: relevance to stress
      adaptation-strategy].

PMID- 18326299
TI  - [Recent progress on structural biology of GPCR: perspectives and limits].

PMID- 18326300
TI  - [Portal services of life science database project in Japan].

PMID- 18326301
TI  - [Regional system for support of home care].
AB  - In order to meet the needs for medical care after discharge from hospital of
      serious or intractable neurological disease patients, in 1978, Shinrakuen
      Hospital in Niigata City launched the Continuing Medical Care Section providing
      home visit by doctors and periodical home nursing. In the article published in
      1990 reporting the 13-year practice of this section, the author advocated the
      necessity of the across-the-board and continuing regional care system in support
      of homecare and proposed a desirable model. Since then, with the policy shift
      from hospital care to homecare facing the progress of aging society, various
      homecare services have been developed. The author opened in 1997 an organized
      clinic of internal and neurological medicine in Niigata City, and, on the basis
      of long term care insurance program founded in 2000, put into practice the
      homecare system of cooperation between the prefectural and municipal
      administration, medicine and nursing. In this article, based on her article in
      1990, the author adds the report on the development of this regional care system
      and evaluates the efficacy of homecare supported by regional system in
      intractable neurological disease medical care.

PMID- 18326302
TI  - [Malignant hyperthermia-like reactions in Duchenne or Becker muscular dystrophy:
      review and hypothesis].
AB  - Adverse reactions to genral anesthesia, which partly resembled malignant
      hyperthermia (MH), were more frequent in muscular dystrophy than in controls. In
      the present study, 35 cases so far reported in Duchenne or Becker muscular
      dystrophy (DMD or BMD) were analyzed and their pathogenesis was discussed.
      Cardiac involvements were sole manifestations in 7 cases. In other 28 cases, the
      acute rhabdomyolysis was the most prevailing manifestation. About 60% of myolysis
      cases were associated with muscle contracture (rigidity) or other hypermetabolic
      signs such as hypercapnia, hyperthermia and metabolic acidosis. Cases with BMD
      were more hyperthermic than with DMD. These results suggest Ca ion-induced
      hypermetabolic reactions are also present in dystrophinopathy, which have been
      assumed as core syndromes of the classical (gene-defined) MH. However, question
      whether the abnormal Ca ion is from the extracellular or intracellular stores is
      still unclear. Circumstancial evidences suggest that the Ca-induced Ca release
      (CICR) mechanism might also be involved. Endogenous redox modulators such as
      nitric oxide or reactive oxygen species in the dystrophic muscle might contribute
      to the perturbed Ca ion homeostasis.

PMID- 18326303
TI  - [Analysis of application form for Parkinson's disease provided by the specific
      diseases treatment research program of Ministry of Health, Labour and Welfare of
      Japan].
AB  - The Ministry of Health, Labour and Welfare (MHLW) of Japan has funded special
      research programs to investigate etiology and treatment of intractable
      neurodegenerative diseases. Individual health-care expenditures for registered
      patients with Parkinson's disease (PD) (Hoehn and Yahr Stage 3-5) have been
      evaluated by the government. The total number of patients registered with a
      diagnosis of degenerative parkinsonism including PD, progressive supranuclear
      palsy (PSP) and corticobasal degeneration (CBD) was 75,026 in 2004. We analyzed
      the data from a survey of application forms completed by 23,058 PD patients,
      which had been entered into the MHLW's computer. The male to female ratio was 1:
      1.47, and the mean ages of all patients at registration and at onset were 71.3
      years and 62.7 years, respectively. Incidence of young-onset Parkinson's disease
      was 2.7% of all PD patients. The percentage of PD patients at Hoehn and Yahr
      Stage 3 was 48.8%, at Stage 4, 23.1%, and at Stage 5, 25.2%. About 60% of
      patients resided at home, whereas 20% were admitted into the hospital and 20%
      into a nursing home. The percentages of patients with diurnal fluctuations,
      dyskinesia and psychotic symptoms were 37.3%, 16.8% and 18.4%, respectively. Ages
      of patients at registration and at disease onset who presented with diurnal
      fluctuations and dyskinesia were typically younger and the duration of disease
      was longer than for those presented without them (p < 0.0001). Patients with
      psychotic symptoms were older and the duration of disease was longer than those
      without them (p < 0.0001). Ages of patients receiving ablative surgery were
      younger than those who received deep brain stimulation (DBS) (57.4 versus 63.1
      years, p < 0.01). Approximately 70% of all the patients who underwent
      stereotactic surgeries were treated within 10 years from onset. The percentage of
      patients with feeding tube was 6.6%, and the age at registration was older (75.6
      versus 71.0 years, p < 0.0001) and duration of disease was longer (11.0 versus
      8.4 years, p < 0.0001) in patients with feeding tube than in patients with oral
      feeding. This is the first analysis of results from the survey of questionnaire
      for PD provided by MHLW.

PMID- 18326304
TI  - [Clinical and pathological significance of carotid siphon calcification observed
      on bone condition of brain CT].
AB  - PURPOSE: On plain brain computed tomography (CT), it is difficult to evaluate
      stenosis of internal carotid artery (ICA) because ICA is surrounded by
      structures, even though we can observe calcification of carotid siphon in some
      patients by using bone condition. However the pathologic significance has not
      been well known. We studied the pathologic significance of carotid siphon
      calcification observed on bone condition of brain CT. METHODS: A total of 112
      patients who were diagnosed or suspected as cerebrovascular diseases were
      registered. We classified the calcification into four levels (none, mild,
      moderate, severe) based on the degree of calcification. Then we compared it with
      the degree of stenosis of carotid siphon seen on brain magnetic resonance
      angiography (MRA) and with max intima-medial thickness (IMT) from common carotid
      artery (CCA) to ICA on carotid ultrasonography. RESULT: The mean +/- standard
      deviation of max IMT to none, mild, moderate and severe in the degree of
      calcification were 1.03 +/- 0.64 (0.4-2.8), 1.65 +/- 0.83 (0.5-4.1), 2.03 +/-
      0.83 (0.8-4.1) and 2.81 +/- 1.15 (0.7-6.5) mm, respectively. The calcification on
      brain CT significantly correlated with the degree of stenosis on brain MRA and
      with max IMT on carotid ultrasonography. CONCLUSION: The calcification of carotid
      siphon on bone condition of brain CT correlated with stenosis of the same portion
      and atherosclerosis of CCA bifurcation. Recently, on DICOM viewer, clinicians can
      convert plain condition into bone condition on brain CT due to popularization of
      PACS. We should pay attention to calcification of carotid siphon in patients with
      ischemic cerebrovascular diseases because we can estimate the atherosclerosis of
      both carotid siphon and CCA bifurcation easily and immediately.

PMID- 18326305
TI  - [Detection of the primary tumor site in tumor-induced osteomalacia by indium-111
      octreotide scintigraphy: a case report].
AB  - We report a 31-year-old woman with tumor-induced osteomalacia suffering from
      slowly progressive bilateral muscle weakness predominantly in the proximal
      muscles and multiple bone pains for the past 2 years. She was unable to walk or
      raise her arms above the shoulder. We suspected tumor-induced osteomalacia due to
      decreased serum phosphate and 1alpha, 25 (OH),-vitamin D3 levels, low percentage
      of tubular reabsorption of phosphate (%TRP), adult onset, and no family history
      of osteomalacia. Regular imaging examinations could not detect the location of
      the primary tumor: however, indium-111 octreotide scintigraphy detected the
      causative primary mesenchymal tumor in the right sole. Pain and muscle weakness
      improved promptly after tumor resection, and she was able to walk 6 d
      postoperatively. This is the first case report in Japan describing the detection
      of the primary tumor site by indium-111 octreotide scintigraphy.

PMID- 18326306
TI  - [Case of an 81-year-old woman with theophylline-associated seizures followed by
      partial seizures due to vitamin B6 deficiency].
AB  - We report an 81-year-old woman who suffered from theophylline-associated seizures
      followed by partial seizures due to vitamin B6 deficiency. She developed complex
      partial seizures. She had been treated with theophylline for two months because
      of chronic bronchitis. Brain diffusion-weighted magnetic resonance imaging (MRI)
      showed high intensity lesions in unilateral cerebral cortex and thalamus.
      Electroencephalogram presented periodic lateralized epileptiform discharges
      (PLEDs), and single photon emission computed tomography (SPECT) using 123I-IMP
      revealed increased blood flow in the same side of the cerebrum. We diagnosed as
      theophylline-associated seizures though blood theophylline concentration
      disclosed its therapeutic dose, and her symptom improved after theophylline was
      discontinued. She developed partial seizures again, after she suffered from
      diarrhea for two days. Laboratory examination showed that serum vitamin B6 was
      under the limitation of measurement, and intravenous supplementation of vitamin
      B6 stopped her seizures immediately. Theophylline may induce seizures independent
      of its blood concentration, and vitamin B6 deficiency may exist in the case of
      theophylline-associated seizures.

PMID- 18326307
TI  - [Case of atopic myelitis with acute onset and atypical distribution of spinal
      cord lesions].
AB  - A 23-year-old woman was admitted to our department because of gait disturbance,
      sensory impairment in the lower limbs, and sphincter disturbance, all of which
      had been developing within 24 hours before admission. Neurological examination
      disclosed symmetric muscle weakness, sensory impairment, and diminished tendon
      reflexes in the lower limbs. The urinary bladder was hypoactive, and the anal
      tone was reduced. The spinal cord MRI performed on the day of admission revealed
      swelling of the epiconus. The CSF findings were not remarkable, except for the
      elevated levels of IgE (8 IU/ml) and MBP (7.8 ng/ml). Besides, there was a marked
      increase in the serum mite-specific IgE titers. Collectively, we made a diagnosis
      of atopic myelitis. She was treated with steroid pulse therapy and plasma
      exchange, which led to a significant amelioration of her neurological
      manifestations. The repeat MRI carried out on the 21st day of her admission
      displayed several foci scattered in the lumbar and sacral spinal cord segments,
      which exhibited high intensity signals on the T2-weighted images. The values of
      IgE and albumin in the CSF and serum raised the possibility of intrathecal IgE
      synthesis. We measured her CSF IgE levels at several time points during
      admission. The temporal profile of her CSF IgE levels was not correlated with
      that of her neurological disabilities.

PMID- 18326308
TI  - [Case of pontine infarction causing alternating hemiplegia with ipsilateral
      abducens nerve palsy and contralateral supranuclear facial nerve palsy].
AB  - We report a 73-year-old man with alternating abducent hemiplegia (Raymond
      syndrome) and contralateral supranuclear facial nerve palsy. On admission, he
      showed lateral gaze palsy of the right eye, left supranuclear facial nerve palsy,
      dysarthria and left hemiparesis. Brain MRI showed an infarct that was located in
      the paramedian and lateral area in the base of the caudal pons on the right side.
      MRA showed a mild stenosis of the basilar artery. Hemiplegia and supranuclear
      facial nerve palsy were considered to be caused by the involvement of
      corticospinal tract and corticobulbar tract that run at the ventromedial area of
      the pons. Abducens nerve palsy was considered to be caused by the involvement of
      infranuclear abducens nerve fibers. There has been one previously reported case
      of Raymond syndrome in which MRI determined the precise location of the lesion.
      In this case, a small hematoma was found at the ventral and medial pontomedullary
      junction, whereas the infarct in our case was located in the pontine base. We
      considered that documentation of our case was an important contribution to
      determine the pathogenesis of supranuclear facial nerve palsy due to caudal
      pontine lesions.

PMID- 18326309
TI  - [Impaired recognition of emotion improved by L-DOPA in a patient with amygdala
      damage].
AB  - We examined the effect of levodopa (L-DOPA) in a patient with a lesion of the
      amygdala and impaired recognition of emotion. Before L-DOPA, recognition of fear
      and disgust was significantly impaired compared to recognition scores in
      controls. After receiving L-DOPA, the patient showed normal recognition of fear
      and disgust. After the drug wore off, recognition declined to her initial
      unmedicated performance. We hypothesized that L-DOPA may have activated
      dopaminergic systems involved in recognition of emotion such as the medial
      prefrontal cortex and anterior cingulate cortex, compensating for the amygdala
      dysfunction. Alternatively. L-DOPA may have activated intact portions of the
      amygdala.

PMID- 18326310
TI  - [Low dose pergolide induced systemic edema and pleural effusion in a patient with
      Parkinson's disease].
AB  - A 77-year-old woman was admitted to our department due to leg edema of 2-year
      duration. The patient has been suffered from Parkinson's disease for 12 years and
      prescribed levodopa, selegiline, and small dosage of pergolide (200 microg/day).
      Leg edema developed one year after she took pergolide. Bilateral peripheral
      effusion was shown without any findings for malignancy, infection, and heart
      failure. After discontinuation of pergolide, both pleural effusion and systemic
      edema were solved. Pergolide was reported to cause cardiac valve fibrosis,
      pleural effusion and fibrosis, and peritoneal fibrosis. This case suggests that
      low dose pergolide (200 microg/day: cumulative dose is about 200 mg) could cause
      severe pleural effusion and systemic edema.

PMID- 18326311
TI  - [Regulation of erythropoiesis and pathogenesis of anemia].

PMID- 18326312
TI  - [Pathophysiology, diagnosis and treatment of anemia].
AB  - Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic
      syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD),
      thalassemia, megaloblastic anemia, chronic renal failure, hematological
      malignancies, etc.], excessive RBC destruction [hereditary spherocytosis,
      inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia
      (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based
      on the measured red cell size(MCV), anemia is classified as microcytic,
      normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.),
      reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12
      level, and Ham test are also useful in the differential diagnosis of anemia.
      Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for
      high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed
      for the treatment of transfusional iron overload is also very useful for the
      management of patients with bone marrow failure syndromes.

PMID- 18326313
TI  - [Overview of the clinical reference guides for the idiopathic hematopoietic
      disorders].
AB  - The research committee for idiopathic hematopoietic disorders, which has been
      supported by the government over the past 35 years, has recently worked out a
      series of reference guide for the management of diseases under investigation to
      provide aids for better understanding of pathophysiology of diseases and
      appropriate clinical decision making. Such attempts covered aplastic anemia,
      Fanconi anemia, pure red cell aplasia, autoimmune hemolytic anemia, paroxysmal
      nocturnal hemoglobinuria, myelodysplastic syndromes and primary myelofibrosis,
      and included diagnostic criteria and severity classification as well as clinical
      pictures derived from nationwide survey studies. Therapeutic measures were
      evaluated according to the concepts of evidence-based medicine, when applicable.
      This report presents an overview of these guides and summarizes key issues in
      each disease entity.

PMID- 18326314
TI  - [Hematopoietic stem cell].
AB  - Hematopoietic stem cells (HSCs) maintain themselves over cell divisions (self
      renewal) and produce all kinds of blood cells (multi-potency). Depletion of these
      cells eventually causes hematopoietic failure, while deregulated HSC division
      causes development of myeloproliferative disorders and leukemias. HSCs can be
      prospectively purified to nearly homogeneity in mice, but such a high-level
      purification has not been achieved in humans. HSCs are localized to an anatomical
      place called 'niche'. Specialized osteoblasts arrayed on the endosteum of
      cavernous bone and sinusoidal endothelial cells located at the distant position
      from the endosteum are the two representative candidates of such an HSC niche. A
      number of adhesion molecules and signaling molecules are thought to comprise the
      niche-HSC synapse. HSCs divide only once in 1-2 months. Both environmental
      signaling from the niche and HSC-autonomous molecular programs contribute to the
      quiescent state of HSCs, which is essential for the maintenance of HSC self
      renewal capacity and homeostasis of blood production.

PMID- 18326315
TI  - [Hematopoietic growth factors, cytokines, and bone-marrow microenvironment].
AB  - Erythroid development is influenced by cytokines: erythropoietin (Epo) and stem
      cell factor (SCF), which works synergistically. Epo is the major regulator of
      erythropoiesis, which is produced by kidneys with an inverse relation to oxygen
      availability. The Epo gene expression is controlled by HIF-1alpha. After binding
      the Epo-receptor, it activates the JAK2-STAT5 pathway, PI3K-AKT pathway and so
      on. Finally, these signals enhance erythropoiesis. All hematopoietic cells are
      derived from the hematopoietic stem cells (HSCs). HSCs are localizing in a two
      different bone-marrow microenvironment: the osteoblastic niche and the vascular
      niche. The erythroid progenitors are induced from HSCs mainly by the membrane
      bound SCF derived from the bone-marrow stromal cells and then entrapped in the
      extracellular matrix.

PMID- 18326316
TI  - [Immune pathophysiology of refractory anemias].
AB  - Among different immune pathophysiologies of anemia, those of bone marrow failure
      syndromes such as aplastic anemia and myelodysplastic syndrome are most difficult
      to understand. An increase in the proportion of glycosylphosphatidyl-inositol
      anchored protein-deficient cells has been identified as the best marker for the
      presence of immune pathophysiology in this elusive syndrome. The significance of
      detecting small populations of such paroxysmal nocturnal hemoglobinuria (PNH)
      type cells was substantiated by a recent observation that PNH-type cells arose
      from a donor-derived hematopoietic stem cell with a PIG-A mutation in an aplastic
      anemia patient with late graft failure which responded well to immunosuppressive
      therapy. Identification of auto-antigens capable of inducing cytotoxic T cells
      against hematopoietic stem cells is necessary to prove the escape of PIG-A mutant
      clone from the immune system attack using animal models.

PMID- 18326317
TI  - [Iron metabolism and anemia].
AB  - Iron is essential for all living organisms. Iron is taken up from the foods by
      enterocytes of the duodenum and proximal jejunum, and then released into the
      plasma and transported to whole body by binding to transferrin. Transferrin-bound
      iron is utilized mainly for erythropoiesis at the bone marrow, in which iron is
      essential for the formation of heme. Recently, a new anti-microbial peptide,
      named hepcidin, was identified, and hepcidin is found to function as the
      regulator of body iron metabolism by inhibiting iron uptake at enterocyte and
      iron release from reticuloendothelial macrophages. Hepcidin is produced by
      hepatocytes, and the expression is modulated by inflammation so that hepcidin is
      thought to be involved in the pathophysiology of anemia of chronic disease.
      Research in the iron metabolism field has been developing rapidly these years,
      and the new innovational therapies for the disease caused by the dysregulation of
      iron metabolism are expected.

PMID- 18326318
TI  - [Abnormality of telomere maintenance linked to bone marrow failures].
AB  - Telomeres are structural elements that seal and protect the ends of linear
      chromosomes from illegitimate recombination, end-to-end fusion, or being
      recognized as damaged DNA. These repeats are gradually lost with cellular
      replication and aging. Telomere attrition eventually leads to critically short
      telomeres, inducing cellular proliferative senescence and/or apoptosis possibly
      due to genomic instability. It is thought that telomeres are shortened as a
      result of pathogenic mutations in telomerase gene components which are DKC1,
      telomerase RNA component (TERC), and telomerase reverse transcriptase (TERT), and
      in SBDS gene that lead to an impairment in the proliferative capacity of
      hematopoietic stem cells in patients with inherited and acquired bone marrow
      failures.

PMID- 18326319
TI  - [Aplastic anemia and pure red cell aplasia].
AB  - Aplastic anemia (AA) is a disorder characterized by the presence of pancytopenia
      and a hypocellular bone marrow. Acquired pure red cell aplasia (PRCA), a part of
      a unique form of AA, is a rare condition of profound anemia characterized by the
      absence of reticulocytes and the virtual absence of erythroid precursors in the
      bone marrow. AA can be effectively treated by either stem cell transplantation or
      immunosuppressive therapy. However, PRCA has so far been treated by several
      different regimens which are largely empirically selected since so little control
      data are available. This issue focuses on the current progress in the treatment
      of acquired AA and PRCA.

PMID- 18326320
TI  - [Autoimmune hemolytic anemia].
AB  - Diagnosis of autoimmune hemolytic anemia (AIHA) requires both serologic evidence
      of an autoantibody and hemolysis. Based on the characteristic temperature
      reactivity of the autoantibody to red cell membranes, AIHA is classified into
      warm AIHA or cold AIHA (cold agglutinin disease and paroxysmal cold
      hemoglobinuria). Sensitized RBCs are destructed by intravascular and/or
      extravascular hemolysis. On the basis of etiology, AIHA are classified as
      idiopathic or secondary. The common cause of secondary AIHA is
      lymphoproliferative disorders, autoimmune diseases, and infections. The first
      line therapy of patients with warm AIHA is glucocorticoids and primary treatment
      for cold AIHA is avoiding cold exposure. The other standard treatments include
      splenectomy and immunosuppressive drugs. Recently, rituximab, a monoclonal anti
      CD20 antibody, has been used in refractory AIHA with excellent responses.

PMID- 18326321
TI  - [Digestive disease with anemia].
AB  - Anemia is often observed in digestive diseases such as gastroduodenal ulcers,
      esophageal varices, atrophic gastritis, malignant neoplasms, inflammatory bowel
      diseases, gastrectomy, malabsorption syndrome, and liver diseases. Anemia in
      these digestive diseases is caused by bleeding, iron deficiency, vitamin B12
      deficiency including pernicious anemia, chronic inflammation (anemia of chronic
      disorders), malnutrition, hypersplenism. Especially in case of gastrointestinal
      bleeding, double balloon enteroscopy has been recently introduced to contribute
      to the diagnosis and treatment as well as gastroendoscopy and colonoscopy. In the
      treatment of digestive disease with anemia, it is important to treat digestive
      diseases appropriately. In treatment of patients with anemia of unknown origin,
      examinations about digestive diseases should be considered.

PMID- 18326322
TI  - [Pathogenesis of anemia of chronic disease].
AB  - Anemia of chronic disease (ACD) is a mild to moderate anemia seen with many
      infections and inflammatory disorders. These patients have low serum iron, but
      high serum ferritin levels. As for the pathogenesis of ACD, previous studies have
      reported several abnormalities, such as insufficient EPO production, impaired
      growth response of erythroid progenitors to EPO, and shortened survival of
      erythrocytes, due to the inflammatory cytokines. However, recent analyses have
      clearly shown that hepcidin, of which expression is induced by inflammatory
      cytokines such as IL-1beta and IL-6, suppresses the expression of the iron
      transporter, ferroportin-1, thereby inhibiting the absorption of iron from the
      duodenum, the release of iron from the reticulo-endothelial system. So, the
      abnormal expression of hepcidin alone may be able to explain the unique iron
      metabolism in ACD.

PMID- 18326323
TI  - [Drug-induced anemia].
AB  - Drug-induced anemia includes many kind of anemias with different mechanisms.
      Mechanisms of drug-induced anemia are divided into two groups, namely erythrocyte
      injury in peripheral blood and damage of erythroid progenitor cells or
      erythroblasts. Hemolytic anemias are included in the former and megaloblastic
      anemia, ringed sideroblastic anemia and pure red cell aplasia are included in the
      latter. When the drug induced anemia is suspected, complete blood cell count
      including reticulocyte count and examination of the blood smear and blood
      chemistry tests should be done. Also, history of the medication should be
      precisely taken. As for the treatment of drug-induced anemia, the responsible
      drug should be stopped immediately and individual therapy will be done if
      necessary.

PMID- 18326324
TI  - [Anemia in children].
AB  - Anemia is one of the most common symptoms in children caused by numerous
      underlying diseases. In majority of patients, these diseases can be correctly
      diagnosed through physical examination, history taking, and routine laboratory
      tests. Bone marrow failure syndromes associated with several genetic diseases are
      rare causes of anemia in childhood. We reviewed the recent progress of molecular
      mechanisms in bone marrow failure syndromes, such as Shwachman-Diamond syndrome
      (SDS), Diamond-Blackfan anemia (DBA), and dyskeratosis congenita (DC), which are
      all predicted to involve defective ribosome synthesis. Delineation of the precise
      role of each gene product in ribosomal biogenesis and hematopoiesis may have both
      therapeutic and prognostic significance.

PMID- 18326325
TI  - [Anemia in the field of obstetrics and gynecology].
AB  - Gynecological anemia is caused by hypermenorrhea. Not only gynecological diseases
      such as uterine myoma, adenomyosis and endometrial hyperplasia but also
      polymenorrhea often show hypermenorrhea resulted in iron-deficiency anemia.
      Pregnant women often show iron-deficiency anemia. However, this anemia is known
      as a physiological one resulted in hemodilution with increased plasma volume
      during pregnancy to maintain utero-placental circulation.

PMID- 18326326
TI  - [Guidelines for transfusion and their significance].
AB  - The guidelines for blood transfusion practice and the guidelines for usage of
      blood products were revised and issued by Ministry of Health, Labor and Welfare
      in 2005. The purposes of these guidelines are to provide safe and appropriate
      transfusion therapy to the patients. All physicians and healthcare professionals
      who are involved in transfusion therapy should learn the concept of these
      guidelines and think carefully about the indication of blood products.

PMID- 18326327
TI  - [Iron overload and iron chelation therapy in transfusion-dependent patients].
AB  - Many patients with bone marrow failure need repetitive transfusion of red blood
      cells and most of them finally suffer from organ dysfunction induced by
      excessively accumulated iron. The only way to treat iron overload caused by blood
      transfusion is iron chelation therapy. But most patients have not been treated
      sufficiently, because optimal administration of deferoxamine, the only iron
      chelator available in Japan, is difficult for many reasons. Recently, a novel
      oral iron chelator, deferasirox has been developed, and it is expected to improve
      chelation therapy in Japan in the near future. In this review, I will discuss the
      current and future status of iron overload and iron chelation therapy in
      transfusion-dependent patients. I will also introduce a proposed guideline for
      the diagnosis and treatment of iron overload in Japan.

PMID- 18326328
TI  - [Development trend in new therapeutic approaches for anemia].
AB  - For cancer treatment-related anemia, it is recommended to use erythropoietin or
      darbepoetin alpha by the National Comprehensive Cancer Network (NCCN). The
      guideline proposed the risk assessment for anemia, as well. The introduction of
      erythropoietin or darbepoetin alpha for anemia in treated cancer patients is
      based on the improvement of quality of life. For patients with myelodysplastic
      syndrome (MDS), those with 5q- anomaly is recommended to use lenalidomide and low
      risk MDS patients without 5q- and serum erythropoietin of less than 500 mU/ml are
      recommended to treat with erythropoietin or darbepoetin alpha. These new agents
      are currently under clinical trials in Japan.

PMID- 18326329
TI  - [Allogeneic stem cell transplantation for severe aplastic anemia and
      myelodysplasia].
AB  - Stem cell transplantation is an effective treatment for anemia associated with
      stem cell disorders such as severe aplastic anemia, myelodysplastic syndrome.
      Long-term survival rates after transplantation for those diseases range from less
      than 40% to more than 80%. The rates are significantly affected by recipient's
      age, HLA disparity between donor and recipient, sources of stem cells, and
      disease status. Results are best in younger patients transplanted with bone
      marrow from HLA-identical sibling at the early course of the diseases. The
      decision of whether and at what point to proceed to transplantation should be
      made early after diagnosis, based upon the consideration of a survival rate with
      reasonable quality of life expected with transplantation and other therapeutic
      approaches.

PMID- 18326330
TI  - [Iron deficiency anemia and H. pylori].
AB  - Although Helicobacter pylori (H. pylori) is a causative agent for chronic
      gastritis, peptic ulcer, and gastric carcinoma, this pathogen is also responsible
      for some extra-gastric diseases. Both epidemiologic and clinical studies suggest
      that H. pylori infection is a risk factor for iron deficiency anemia (IDA).
      Several case reports and case series showed reversal of IDA after eradication of
      H. pylori. Although the mechanisms for H. pylori-associated IDA is not fully
      understood, H. pylori-induced chronic pangastritis with resultant achlorhydria
      and reduced ascorbic acid secretion in the gastric mucosa may lead to reduced
      iron absorption. Uptake of iron by H. pylori is also suggested. Further properly
      designed trials are needed to confirm a causal relationship between H. pylori and
      IDA.

PMID- 18326331
TI  - [Significance of treating prehypertension with an angiotensin-receptor blocker-
      results from TROPHY study].
AB  - Prehypertension is considered a precursor of stage 1 hypertension and a predictor
      of excessive cardiovascular risk. TROPHY study investigated whether pharmacologic
      treatment of prehypertension prevents or postpones stage 1 hypertension.
      Treatment of prehypertension with angiotensin receptor blocker (ARB): candesartan
      monotherapy decreased incident hypertension in participates in the study. On the
      other hand, DHyPP study investigated whether early treatment with an ARB in young
      normotensive off spring of hypertensive parents persistently lowered blood
      pressure after treatment withdrawn, a possibility supported the animal study and
      found no persistent effect on blood pressure when treatment was withdrawn. Thus
      these studies have demonstrated the feasibility of treating prehypertension with
      an ARB, but inconsistent results of the persistent effect on blood pressure when
      treatment was withdrawn. Thus additional studies will be needed to ascertain
      whether this or other strategies involving early pharmacologic treatment of
      prehypertension would positively affect clinical outcomes as well as blood
      pressure.

PMID- 18326332
TI  - [Stability for long-term storage and reproducibility of positivity in the panel
      test slide prepared with the polyacrylamide-based artificial sputum].
AB  - OBJECTIVE: A novel artificial sputum has been developed using polyacrylamide,
      cultured THP-1 cell and BCG-Pasteur. Smears prepared with this artificial sputum
      are similar to actual sputum and has feasibility to set any positivity grades.
      Long-term storage and reproducibility of the positivity was examined to support
      further availability. METHOD: The artificial sputa were stored for up to 9 months
      at room temperature, 4 degrees C and -20 degrees C. Then, smears were prepared
      and their macroscopic and microscopic appearance were examined compared with
      smears from freshly prepared artificial sputum. Furthermore, smears with
      different positivities (+/-, 1 +, 2 + and 3 +) were prepared and examined by
      several trained technicians, and the reproducibility of the original sputum
      positivity was determined. RESULTS: Macroscopic and microscopic appearance of
      smears prepared from long-term stored artificial sputum showed little changes
      compared with smears of freshly prepared artificial sputum. The positivity of
      these smears fell in their original grade. A total of 91 smears were prepared
      from artificial sputum with different positivity and examined by trained
      technicians. Although 3 out of 36 +/- smears were determined as negative, all of
      the remaining smears were evaluated correctly. DISCUSSION: This study confirmed
      that the artificial sputum and the smears have long-term storage stability and
      reproducibility in the positivity. These results suggest that the artificial
      sputum can be widely used to perform external quality assessment in many
      countries, including high prevalence countries.

PMID- 18326333
TI  - [A study on clinical features of Mycobacterium kansasii pulmonary disease in
      women].
AB  - OBJECTIVES: To clarify clinical features of M. kansasii pulmonary disease in
      women. METHODS: We performed a retrospective analysis of M. kansasii pulmonary
      disease in women compairing with that in men. We focused on 8 female cases of M.
      kansasii pulmonary disease during the past 7 years from June 1998 to August 2005.
      RESULTS: The cases of M. kansasii pulmonary disease in women have increased in
      the latter few years. The mean age of female cases was higher than that of male
      cases, 65.6 and 53.1 years old, respectively. The number of female cases with
      smoking history was lower than that of male cases, 37.5% and 90.0%, respectively.
      Two female cases had underlying pulmonary diseases, as compared with 10 male
      cases, 25.0% and 33.3%, respectively. The radiological findings in female cases
      included 2 cavitary opacities, 1 infiltrative opacity and 5 nodular,
      bronchiectatic opacities, as compared with 27 cavitary opacities, 1 infiltrative
      opacity, 1 solitary nodular opacity and 1 nodular, bronchiectatic opacity in male
      cases. MAC was also detected in 2 female cases, who presented with nodular,
      bronchiectatic opacities. On the other hand, there were 6 female cases, in which
      no other NTM was detected. 3 cases showed cavitary or infiltrative opacities,
      which improved with the following 3 tuberculous drugs INH, RFP, and EB (HRE),
      while others showed nodular, bronchiectatic opacities, in which 2 cases showed
      radiological exacerbations without any treatment and another one revealed an
      improvement with HRE. CONCLUSIONS: M. kansasii pulmonary disease in women tends
      to be identified in elderly who smoke less and have no underlying pulmonary
      diseases, and most of radiological findings in female cases revealed nodular,
      bronchiectatic opacities. Summing up all these findings, clinical features of M.
      kansasii pulmonary disease in women was considered to resemble that of MAC
      infection, and it was speculated that the increase of M. kansasii pulmonary
      disease in women has some relationship with that of MAC infection in middle or
      lingular lobe. However, it was confirmed that some cases of M. kansasii pulmonary
      disease in women might primarily present with nodular, bronchiectatic lesions,
      regardless of MAC infection.

PMID- 18326334
TI  - [Transmission of tuberculosis from smear-negative bacillus-positive pulmonary TB
      patients].
AB  - OBJECTIVES: To elucidate TB transmission from smear-negative bacillus-positive
      patients. SUBJECTS AND METHODS: The subjects of this retrospective study were
      8,339 TB patients registered in Aichi Prefecture between 1989 and 2003. Of these
      patients, 7,122 had pulmonary TB and 1,217 had extra-pulmonary TB.
      Bacteriological examination for the pulmonary patients revealed sputum smear
      positive in 2,640, sputum smear-negative bacillus-positive (SNBP) in 1,794, and
      smear-negative bacillus-negative (SNBN) in 2,688. All registration files were
      reviewed to identify epidemiological links of patients. When linked patients with
      an interval of the dates of registration of less than 10 years were found, the
      initial case was considered as the index case, and the other patients were
      regarded as secondary cases. An index case rate (ICR) for a category of patients
      was defined as follows; ICR=NI/NA, where NA: Number of TB patients in a category
      A, and NI: Number of index cases in category A. RESULTS: A total of 287 patients
      were considered as index cases, and the ICR was 3.4%. The ICRs were 2.3% for the
      SNBP patients, 7.5% for the smear-positive patients, 1.2% for the SNBN patients,
      and 1.1% for the exrtra-pulmonary tuberculosis patients. The SNBP patients had a
      significantly higher ICR than the SNBN patients (p<0.01), and a significantly
      lower ICR than the smear-positive patients (p<0.001). In the SNBP patients, the
      ICRs were 5.0% for those aged 40 to 49 years and 1.6% for those aged 50 to 59,
      and the difference was statistically significant (p<0.05). All patients were
      grouped into two groups; younger patients with an age of less than 50 years and
      elder patients with an age of 50 years or higher. The ICRs showed significant
      differences between the younger patients and the elder patients as follows: 4.3%
      vs 1.7% for the SNBP patients (p<0.01), 15.5% vs 5.0% for the smear-positive
      patients (p<0.001), and 1.9% vs 0.9% for the SNBN patients (p<0.05). The chest X
      ray showed cavitary lesion in 453 SNBP patients. The ICRs were 8.7% for 126
      cavitary younger SNBP patients, 2.6% for 311 non-cavitary younger SNBP patients,
      2.4% for 327 cavitary elder SNBP patients, and 1.5% for 1,030 non-cavitary elder
      SNBP patients. The ICR for the cavitary younger SNBP patients was significantly
      higher than those for the other three subgroups (p<0.01 to p<0.001). CONCLUSION:
      These findings suggest that TB transmission from SNBP patients depends on the
      patient's age and the cavity formation, and that patients aged less than 50 years
      with cavitary pulmonary TB is the most important target for the epidemiological
      research.

PMID- 18326335
TI  - [A case of adrenal tuberculosis complicated with acute exacerbation of adrenal
      insufficiency during the initial phase of anti-tuberculosis therapy for pulmonary
      tuberculosis].
AB  - A 36-year-old male was admitted to our hospital because of adrenal insufficiency.
      About one month before admission, he was diagnosed as pulmonary tuberculosis and
      started anti-tuberculosis therapy with isoniazid, rifampicin, ethambutol, and
      pyrazinamide. On the tenth day, general fatigue, abdominal pain, nausea and
      diarrhea developed, and laboratory examination showed hyponatremia [126 mEq/l].
      Enhanced CT on admission revealed bilateral adrenal mass-like enlargement, and
      further examination showed high level of plasma ACTH, and low level of cortisol.
      These findings led to a diagnosis of adrenal insufficiency caused by adrenal
      tuberculosis. He was treated with hydrocortisone and his signs and symptoms
      rapidly improved. We suppose adrenal insufficiency became clinically apparent
      because rifampicin reduced half-life of serum cortisol. Interestingly we observed
      rapid increase and decrease in size of bilateral adrenal glands on CT scan during
      the course.

PMID- 18326336
TI  - [Tuberculosis elimination in the United States; why, how, and what will it
      take?].
AB  - This overview of tuberculosis elimination in the United States consists of three
      parts. First I will briefly overview the neglect and related factors during
      1970's and early 80's which resulted in the 1985-1992 unprecedented resurgence of
      tuberculosis following thirty years of a steady decline in the United States.
      Second, I will review what we did in response and the resulting trends. Third, I
      will focus on the Institute of Medicine (IOM) report entitled "Ending Neglect",
      and identify the challenges to elimination and what will it take to finishing the
      job. The IOM report recommends the United States to pursue and accelerate the
      elimination of tuberculosis, addressing the following; 1) maintain control while
      adapting to declining incidence of tuberculosis, 2) speed the decline through the
      increased treatment of persons with latent infection, 3) invest in research and
      development to develop new tools needed for ultimate elimination, with a focus on
      new reliable and rapid diagnostic tools for latent infection, new drug regimens,
      especially in light of the emergence of extensively drug-resistant tuberculosis,
      and a safe and effective vaccine for tuberculosis, 4) increase the United States
      engagement in global efforts, recognizing that the global reality is directly
      reflected in the United States, 5) mobilize support and measure progress towards
      elimination. Each of these recommendations will be translated into the agenda for
      action with the illustrations for the real situations of the United States. It is
      important to recognize that in spite of all this progress much work needs to be
      done and in order to finish the job on tuberculosis elimination we have the
      blueprints, we have the partners, and we must keep working to make the effective
      use of our resources. I would like to close by quoting one of the favorite
      phrases in "Ending Neglect"; "The issue now confronting the nation, that is the
      United States, is whether we will allow another cycle of neglect to begin or
      instead whether we will take decisive action to eliminate tuberculosis."

PMID- 18326337
TI  - [Innate immunity and tuberculosis].
AB  - The immune system is divided into innate and adaptive immunity. The innate immune
      system provides the first line of host defense against invading microorganisms
      before the development of adaptive immune responses. Innate immune responses are
      initiated by germline-encoded pattern recognition receptors (PRRs), which
      recognize specific structures of microorganisms. Toll-like receptors (TLRs) are
      one of the family of pattern-recognition receptors to sense a wide range of
      microorganisms, such as bacteria, fungi, protozoa and viruses. Recognition of
      Mycobacterium tuberculosis components by TLRs triggers activation of signal
      transduction pathways, which then induces dendritic cell maturation and cytokine
      production, resulting in development of adaptive immunity. TLRs are critically
      involved in the induction of host defense to M. tuberculosis.

PMID- 18326338
TI  - [Human rights of patients and tuberculosis prevention].
AB  - The Act for Prevention and Medical Treatment of Patients of Infectious Diseases
      in Japan was revised in December 2006. Through this revise of the act, the
      articles for the measures against Bio-terrors were incorporated into the act, and
      the idea of respect of human rights of patients surely took root into the act. At
      the same time, the Tuberculosis Prevention Act was abolished and the articles of
      this act were partly revised and incorporated into the Act for Prevention and
      Medical Treatments of Patients of Infectious Diseases. The procedural rights of
      tuberculoses patients and the role of jurists in the procedure of tuberculosis
      prevention were consolidated. It is desirable that dialogues between jurists and
      those who are engaged in tuberculosis prevention should be accelerated by these
      legislations.

PMID- 18326339
TI  - [Granulomatous diseases and pathogenic microorganism].
AB  - Granuloma formation is a chronic inflammatory reaction where macrophage system
      and other inflammatory cells are involved. After some antigen exposure and
      processing, T cells, macrophages, epithelioid cells, and giant cell are
      activated, and granulomas are formed. Granuloma is considered as a defense
      mechanism against antigens, which stay in the organs without inactivation.
      Granulomas including fibroblasts extra-cellular matrix surround and isolate the
      antigens. Granulomas are classified to noninfectious granulomas and infectious
      granulomas. However recent studies revealed pathogenic microorganism are
      suspected to be a cause of granuloma in non-inflammatory diseases. Balance
      between pathogenic microorganisms and defense mechanisms of the host might be
      important in the special immunologic reaction. In some cases, it is hard to
      clearly classify infectious and noninfectious granulomas. Recently, Eishi et al.
      reported that latent infection of Propionibacterium acnes might be cause of
      sarcoidosis. Several hypersensitivity pneumonias are considered to be caused by
      exogenous microorganisms. The symposium was organized to know and clarify the new
      mechanisms of non-infectious granulomatous lung diseases and pathogenic
      microorganisms. This report is a summary of a symposium entitled "Granulomatous
      Diseases and Pathogenic Microorganism", organized in the 82nd Japanese Society
      for Tuberculosis (president Dr. Mitsunori Sakatani, M.D.). 1. Imaging of
      Granulomatous Lung Diseases: Masanori AKIRA (Department of Radiology, National
      Hospital Organization Kinki-chuo Chest Medical Center) High-resolution computed
      tomography (HRCT) is a useful tool in the evaluation of parenchymal changes in
      patients with a granulomatous lung disease. In sarcoidosis, the HRCT findings
      include small, well-defined nodules in relation to lymphatic roots, lymph node
      enlargement, and middle or upper lobe predominance. The appearances of subacute
      hypersensitivity pneumonitis include ill-defined centrilobular nodules, ground
      glass opacity, and air trapping especially on expiratory CT scan. Those of
      Langerhans cell histiocytosis include bizarre thin-walled lung cysts,
      centrilobular nodules and upper lobe predominance. Each of granulomatous lung
      disease has some characteristic HRCT appearances, but they all are non-specific
      for diagnosis. HRCT is also useful for grading of parenchymal changes in
      granulomatous lung diseases. 2. Histopathology of granulomatous lung diseases
      with special reference to differential diagnosis of infectious disease: Tamiko
      TAKEMURA (Department of Pathology, Japanese Red Cross Medical Center) The lung is
      commonly involved by various granulomatous diseases of various etiology. It is
      difficult to pathologically differentiate these granuloumatous diseases to
      conduct appropriate therapy, because of morphological similarity of epithelioid
      cell granuloma, variable etiology, and difficulty of identification of causative
      agents. Granulomatous diseases generally are divided into infectious and non
      infectious ones for treatment. Although infectious granulomas usually reveal
      necrosis and abscess, non-infectious ones occasionally also reveal necrosis. In
      cases with granulomas in the lung, it is necessary to explore the etiologic
      agents including environmental ones. 3. Sarcoidosis and Propionibacterium acnes:
      Yoshinobu EISHI (Department of Pathology, Tokyo Medical and Dental University) P.
      acnes can cause latent infection in peripheral lung tissue and the mediastinal
      lymph nodes and persist intracellularly in a cell-wall-deficient form. This
      dormant form of P. acnes can be activated endogenously under certain
      environmental conditions (hormones, stress, living habits, etc.) and proliferate
      in cells at the sites of latent infection. Granulomatous inflammation occurs in
      sarcoidosis patients with hypersensitivity to intracellular proliferation of the
      cell-wall-deficient bacteria, which can infect other cells or organs when spread
      via the lymphatic or blood streams. The timely use of antibiotics may not only
      kill the bacteria proliferating at the site of disease activity, but also prevent
      endogenous activation of P. acnes. If long term administration of antibiotics
      eradicates dormant forms of the bacteria persistent in organs, it may lead to
      complete remission of sarcoidosis. 4. Farmer's lung and thermophilic
      actinomycetes: Takashi MOURI (Pulmonary Division, Iwate Prefectural Kitakami
      Hospital), Kohei YAMAUCHI, Hiroshi INOUE (Third Department of Internal Medicine,
      Iwate Medical University, School of Medicine), Kazuki KONISHI (Morioka Tsunagi
      Onsen Hospital) Farmer's lung is caused by the allergic reaction to inhalation of
      thermophilic actinomycetes. Acute symptoms are chill, fever, cough and dyspnea.
      Fine crackles is characteristic. Pathologically, alveolitis with lymphocytes
      infiltration and epithelioid cell granuloma and Masson's body are
      characteristics. Bronchoalveolar lavage analysis shows elevated lymphocytes and
      diverse CD4/8 ratio (high in average). Isolation from the environment improves
      the symptoms. Sometimes patients need steroid therapy, 0.5 to 1.0 mg/kg of
      predonisolone. Pulse therapy can be applied for severe cases. SLX analogue can
      prevent lymphocytes infiltration and granuloma formation in mice model. Some of
      acute farmer's lung show poor long term prognosis, showing emphysematous, fine
      granular or small nodules in chest CT. These chronic farmer's lung might be
      diagnosed as IIPs. 5. Hot tub lung: Takashi OGURA (Kanagawa Cardiovascular and
      Respiratory Center) Hot Tub Lung (HTL) is a disorder caused by exposure to
      Mycobacterium avium complex (MAC) organisms contaminating hot tub water. Whether
      this disease represents true infection or hypersensitivity pneumonitis is
      contoroversial. Recent reports support the theory that this disease represents a
      hypersensitivity pneumonitis rather than infection. The physicians should suspect
      a hypersensitivity pneumonitis reaction to MAC in the investigation of patients
      with hypersensitivity pneumonitis of unknown cause.

PMID- 18326340
TI  - [Petrous cholesteatoma: clinical features and surgical outcome].
AB  - In this study we analyzed the clinical features and surgical treatment of petrous
      cholesteatoma in 9 patients (9 ears) who underwent surgery at the Jikei
      University Hospital. Most patients initially experienced hearing loss, then
      facial nerve palsy or otorrhea. Congenital cholesteatoma was diagnosed in four
      patients, acquired cholesteatoma in one patient, and postoperative recurrence in
      three patients. The proportion of cases of congenital cholesteatomas was higher
      than in previous reports. The area of the cholesteatoma was classified according
      to Dr. Sanna cases and the supralabyrinthine type in two cases. Hearing
      preservation surgery was performed in four patients via the middle cranial fossa
      approach or by partial labyrinthectomy, and the results seemed satisfactory.
      These results suggested that hearing preservation surgery should be adopted in
      every case.

PMID- 18326341
TI  - [Outcomes of endoscopic sinus surgery in chronic sinusitis cases complicated/ not
      complicated by bronchial asthma and eosinophilic infiltration of the sinus
      mucosa].
AB  - BACKGROUND: Intractable sinusitis is, in most cases, complicated by bronchial
      asthma and severe eosinophilic infiltration of the sinus mucosa. Our aim here was
      to study the postoperative outcomes of chronic sinusitis complicated/not
      complicated by bronchial asthma and of cases with eosinophilic sinusitis/non
      eosinophilic sinusitis. METHODS: We conducted a prospective analysis of the
      outcome of 180 patients with or without bronchial asthma and eosinophilic
      infiltration who underwent endoscopic sinus surgery (ESS) for chronic sinusitis.
      The patients were divided into four groups by the presence/absence of asthma and
      presence/absence of eosinophilic infiltration of the sinus mucosa. One surgeon
      performed the ESS, and all the groups received the same postoperative treatment.
      RESULTS: The outcomes of ESS were significantly worse in the cases complicated by
      eosinophilic sinusitis and asthma, especially in relation to the incidence of
      smell disturbances and the endonasal findings. Patients suffering from chronic
      sinusitis without asthma showed good improvement following ESS. There was no
      significant differences in the outcome after ESS between cases of eosinophilic
      sinusitis and those with non-eosinophilic sinusitis among the patients without
      asthma. CONCLUSIONS: We contend that eosinophilic sinusitis without asthma may
      not represent intractable sinusitis. We wish to emphasize that complication by

PMID- 18326342
TI  - Ophthalmic manifestation of aids in Armed Forces General Teaching Hospital, Addis
      Ababa.
AB  - BACKGROUND: The eye is one of the commonly affected organs by HIV/AIDS. However,
      data on HIV/AIDS related ophthalmic lesion is scarce in Ethiopia and in other sub
      Saharan Africa countries, where two-third of the world-infected people are
      living. OBJECTIVE: To determine the proportion, describe the pattern, and assess
      the visual impairment of AIDS related ophthalmic lesions in comparison to CD+ T
      lymphocyte count. METHODS: This is a cross-sectional descriptive study conducted
      on AIDS patients. Consecutive patients whose CD4+ T-lymphocyte count was 200
      cell/microl and below, diagnosed to have AIDS and not started on Antiretroviral
      therapy (ART) were evaluated for ophthalmic lesions over a period of one year.
      RESULTS: A total of 186 (26 females and 160 males) with mean age 34.3 +/- 7.6
      years were examined CD4+ T-lymphocyte was ranging from 1 to 200 cell/microl.
      Sixty-one (32.8%) patients were found to have HIV/AIDS related ophthalmic
      lesions. Four of them had more than one lesion. Among the lesions,
      microvasculopathy (64% of them having CD4 less than 50) was by far the commonest
      accounting for 25/65 (38.1%), followed by Molluscum contageosum of the eyelids
      10/65 (15%). Herpes Zoster Opthalmicus (HZO), uveitis, CMV retinitis were next
      common 4/65 (6.2% each). Eleven unilaterally and two bilaterally were blind. The
      leading cause of blindness was cytomegalovirus retinitis followed by HZO, uveitis
      and presumed toxoplasmisis chorioretinitis. The likelihood of having HIV/AIDS
      related lesion was higher among cases with CD4+ T-lymphocyte count of 50 and
      below (Adjusted OR = 12.25; 95% CI; 1.09, 4.63). CONCLUSION: The presence of
      visual threatening ophthalmic lesions in highly immunocompromised AIDS patient
      shows the importance of early detection and treatment. ART could have impact on
      the pattern of the ophthalmic lesions, hence further study is recommended.

PMID- 18326343
TI  - Determinants of vct uptake among pregnant women attending two ANC clinics in
      Addis Ababa City: unmatched case control study.
AB  - BACKGROUND: With HAART PMTCT interventions can reduce the risk of MTCT below 2%.
      However, low uptake of VCT is challenging effectiveness of PMTCT programs in sub
      Saharan Africa. The aim of this study is to identify factors that determine VCT
      uptake among pregnant women attending ANC services. METHODS: A case-control study
      was conducted from August 30, 2005 - November 30, 2005 among pregnant women
      attending ANC PMTCT services at Teklehaimanot Health Center and Gandhi memorial
      Hospital in Addis Ababa City. Cases were pregnant mothers who accepted VCT
      (n=202) and controls were pregnant mothers who refused VCT (n=200). Data was
      collected by counselor nurses working at the respective services RESULTS: Factors
      that determine VCT acceptance were women's perceived ability to cope with a
      positive result (OR = 5.5, 95% CI 3.5-8.5, MHOR = 6.3, 95% CI 3.9-10.2);
      perceived favorable reaction of husband's after sharing positive test result (OR
      = 2.7 95% CI 1.4-5.1, MHOR = 2.9, 95% CI 1.4-5.7); perceived positive community
      response (OR = 2.2 95% CI 1.1-4.2, MHOR = 2.6 95% CI 1.3-5.2); perceived ability
      to get continuous medical care if found out to be positive (OR = 2.0, 95% CI 1.2
      3.5, MHOR = 2.4, 95% CI 1.3-4.5). CONCLUSION: Women's perceived ability to cope
      with a positive result, accesses to medical care, fear of husband's negative
      reaction and the stigma and discrimination following a positive test result were
      key determinants of uptake of VCT. Therefore, increasing uptake of VCT/PMTCT
      services needs policy makers and service providers' effort to promote couple
      counseling, intensifying the fight against stigma and discrimination and ensuring
      continuous HIV/AIDS related medical care.

PMID- 18326344
TI  - Community perceptions and practices about urban malaria prevention and control in
      Gondar Town, northwest Ethiopia.
AB  - BACKGROUND: Malaria is becoming a major health problem in urban areas. Community
      perceptions, knowledge and practices have a major role in the implementation of
      effective malaria control interventions. Yet little is known about the
      perceptions and practices of urban community about urban malaria prevention and
      control. OBJECTIVE: The aim of this study was to assess the knowledge, attitudes
      and practices of an urban community about malaria prevention and control.
      METHODS: A community-based cross-sectional study was carried out in three
      randomly selected malarious Kebeles of Gondar Town during November-December 2004.
      Knowledge, attitudes and practices were assessed for 489 household members > or
      =18 years old. RESULTS: Almost all respondents knew about malaria and recognized
      it as one of the major health problems of the community. About 58% knew that
      malaria could be transmitted from one person to another, and most (97.2%)
      associated malaria with the bite of mosquito. The most frequently reported
      symptoms of malaria included fever (96.3%), chills and shivering (96.3%),
      headache (96.1%), loss of appetite (92.2%) and joini pain (90.2%). Knowledge
      about the names of the currently used antimalarials, sulfadoxine-pyrimethamine
      (90.4%) and chloroquine (81.6%), was high. About 39% of the total 163 surveyed
      households possessed at least one mosquito net; of these, 55 (83.7%) possessed
      one, 7 (11%) had two and 2 (2.3%) possessed three. Most respondents practiced
      draining stagnant water (46.3%) and clearing vegetation (43.3%) for malaria
      prevention. CONCLUSIONS: Although considerable gaps were observed between
      knowledge and practices of malaria prevention and control methods, community
      knowledge, attitudes and practices on the cause, treatment and prevention of the
      disease were encouraging. Since malaria is identified as a major health problem,
      the use of personal protection methods such as insecticide treated mosquito nets
      should be encouraged through increasing access to it.

PMID- 18326345
TI  - Households willingness to pay for long-lasting insecticide treated nets in three
      urban communities of Assosa Zone, western Ethiopia.
AB  - BACKGROUND: Achieving the target coverage of insecticide treated nets (ITNs) has
      to be preceded by understanding their demands, willingness to pay (WTP) and
      determinants of WTP for those who could not get free of charge. OBJECTIVE: To
      assess WTP for long lasting ITN using contingent valuation method and
      determinants of maximum WTP for long lasting ITN among households in Assosa Zone,
      Western Ethiopia. METHODS: The contingent valuation method was used to assess WTP
      for long-lasting ITN among households selected from the three urban communities.
      univariate and multivariate regression analyses were carried out. The adjusted
      effect (beta), F-ratios, adjusted odds ratios (AOR) and 95% CI were used to
      interpret results. The criterion for statistical significance was set at 0.05.
      RESULTS: Ninety six percent of the respondents reported that long-lasting ITN are
      important for their family fbr prevention of malaria and demanded for long
      lasting ITN. Sixty seven percent of the respondents were willing to pay for long
      lasting ITN at the starting bid amount of 25 Birr. The mean, maximum WTP amount
      was 27.84 Birr. The mean WTP amount varied with the respondents' wealth status,
      which was 19.09 and 35.26 Birr foir poorest and well-off wealth quintiles
      respectively. Wealth status and knowledge of the respondents about its preventive
      effects against boring insects were significantly associated with their WTP
      (adjusted beta = +3.76, 95% CI: 2.3, 4.6 and adjusted beta = 10.15, 95% CI: 2.7,
      17.6 respectively). CONCLUSION: The poor have shown their WTP for reduced cost of
      ITN, thus the regional health bureau should develop a price discrimination
      mechanism for those economically vulnerable groups.

PMID- 18326346
TI  - Antimicrobial resistance patterns of clinical bacterial isolates in southwestern
      Ethiopia.
AB  - OBJECTIVES: The aim of this study was to assess the pattern of bacterial
      resistance to antimicrobial agents in a hospital setting in Southwest Ethiopia.
      METHODS: The antimicrobial resistance pattern of common bacterial isolates was
      determined during January 2003 to July 2004. A total of 291 Gram-positive and
      Gram-negative bacterial strains were isolated from different clinical specimens.
      Specimens collected included ear discharges, throat and wound swabs, as well as
      urine, sputum, stool and blood The specimens were obtained from consecutively
      attending adults and children at the out patient departments of Jimma Hospital.
      The specimens were inoculated onto appropriate culture media. Targeted species
      were identified following standard procedures. Using different panels of
      antibiotics, susceptibility tests were performed using disc diffusion method as
      outlined by Kirby-Bauer method The profile of the commonly prescribed
      antimicrobial agents was studied in accordance with the principles established by
      the National Committee for Clinical Laboratory Standards. RESULTS: One hundred
      seventy six Gram-positive and 115 Gram-negative bacterial species were isolated.
      Of these included Staphylococcus aureus, Coagulase negative Staphylococci and
      Proteus species were isolated frequently in 72 (24.7%), 59 (20.3%) and 55 (18.9%)
      of the isolates, respectively. Antimicrobial susceptibility testes showed that
      methicillin resistant Staphylococcus aureus was found in 8.3% of the cases while
      methicillin resistant coaguuse negative staphylococci were detected in 10.3%. Of
      the Staphylococcus aureus isolates, 90.3% and 91.7% were resistant to penicillin
      and ampicillin, respectively. Two (7.1%) of S. pneumoniae strains and 100% of
      Enterococci were resistant to penicillin. Proteues spp were resistant to
      tetracycline, polymyxin B, chloramphenicol and ampicillin in 90.9%, 92.7%, 67.3%
      and 58.2%, respectively. Escherichia coli, Klebsiella spp and Citrobacter and
      Enterobacter spp were 100% resistant to ampicillin. P. aeruginosa, E. coli,
      Proteus spp, S. aureus and Enterococci spp showed multiple drug resistance. All
      bacterial isolates were susceptible to ciprofloxacin. CONCLUSION: There is an
      increasing trend of antimicrobial resistance in some bacterial species.
      Ciprofloxacin was highly) effective antimicrobial agent in vitro against majority
      of the bacterial isolates. Health personnel should be aware and take necessary
      measures to control further increases in bacterial resistance to antibiotics.

PMID- 18326347
TI  - Spasmolytic effects of artemisia afra and artemisia rehan in tissue preparations.
AB  - BACKGROUND: The genus Artemisia of Family Compositae (Asteracea) is widely used
      in many parts of the world as herbal remedies for a variety of illnesses.
      METHODOLOGY: Ethanol and aqueous extracts of powdered dried leaf and root of
      Artemisia afra and leaf of Artemisia rehan were tested on isolated mouse duodenum
      (MD) and guinea pig ileum (GPI). Different concentrations of each extract of the
      plants (ranging from 20-200 microg/ml) were tested in the presence of agonist
      control, acetylcholine (in MD) and histamine (in GPI) as contraction stimulators.
      RESULTS: Artemisia afra leaf ethanol (ALE) and Artemisia rehan leaf ethanol (RLE)
      significantly reduced both spontaneous rhythmic and agonist-induced contractions
      of MD and GPI. ALE and RLE caused mean contractile response of 44.3 +/- 0.9% (at
      a dose of 160 microg/ml) and 35 +/- 1.8% (at a dose of 120 microg/ml)
      respectively in isolated MD, and a mean contractile response of 60.9 +/- 2.7% and
      43.5 +/- 2.7% respectively at maximal doses of 200 microg/ml in isolated GPI.
      CONCLUSION: The results in the present study indicate that the plants possess
      spasmolytic property and also support the traditional folk use of the aerial and
      root parts of the plants for stomach pains and intestinal cramps.

PMID- 18326348
TI  - Determination of urinary iodine excretion to assess iodine deficiency level and
      iodine intake in primary school children, Bahir Dar, northwest Ethiopia.
AB  - BACKGROUND: Iodine deficiency is a major public health problem all over the
      world, particularly among preschool children and pregnant women in low-income
      countries like Ethiopia and it is known to be the most common cause of
      preventable brain damage. OBJECTIVES: to determine urinary iodine concentration
      and to assess the level of iodine deficiency disorders. METHODS: A cross
      sectional study was conducted in 386 randomly selected primary school children to
      determine urinary iodine concentrations as to assess level of iodine deficiency
      and iodine in take in Bahir Dar town. RESULTS: Median urinary iodine excretion
      was 58.8 mg/L (12.89 mg/L to 564.5 mg/L) which indicated the presence of mild
      iodine deficiency. Eighty seven percent of the children had urinary iodine
      excretion of below 100 mg/L and the intake of iodine was below 150 mg/day.
      CONCLUSIONS: Mild iodine deficiency disorder was found in Bahir Dar primary
      school children, Iodine intake was also found insufficient. Therefore, use of
      salt ionization should be advocated and strengthened.

PMID- 18326349
TI  - Visualization, volume and surface area calculation of three dimensional (3D)
      ultrasound images.
AB  - OBJECTIVE: To segment a 3D ultrasound image data that comprises extraction of
      surface of interests, smoothing of segmented image, thereby to estimate the
      surface area and volume of segmented 3D objects (e.g. fetus). METHOD: (a) Seeded
      Region Growing (SRG) together with connectivity and marching cubes algorithms are
      used to segment the three dimensional (3D) ultrasound image data (I) (b) Using
      VTK (Visualization Tool Kit) a c++ program was developed which relies on the
      Maximum Unit Normal Component (MUNC) used for surface area measurement and
      Divergence Theorem Algorithms (DTA) used for volume estimation. The agreement
      between the program and the formula was tested on (1) computer generated spheres
      and cube (2) cylindrical shaped phantoms scanned by ultrasound scanner System
      Five, GE Vingmed (Horten, Norway) using a 3D annular array of 7.5 MHz. (3) 3D
      ultrasound fetus using cronbach alpha RESULTS: The cylindrical shaped phantom
      (diameter 15.4 mm, length. 21.7 mm) with x and y voxel size 1.24921 mm and
      0.613032 mm respectively and z voxel size 1.249221 mm yield a percentage error of
      5.3% for the surface area and 2.6% for the volume. The volume and surface area of
      the fetus with x, y, z voxel size 0.465508mm, 0.529645 mm, 1.014201 mm
      respectively as estimated with the developed program was 3.758ml for volume and
      1.937 mm2 fbr surface area, while the measured volume of fetus with EchoPAC-3D
      was 3.74 ml. CONCLUSIONS: It was concluded that. The agreement between the
      formula and the program for different shaped objects indicate that the
      methodology can provide measurements of the volume and the surface area of
      different anatomical structures.

PMID- 18326350
TI  - Dicephalus tetrabrachius.
AB  - A 40-year-old Gravida VII, Para VI lady presented to Mekelle hospital after
      pushing down pain of 36 hours. Laparatomy was done after patient was diagnosed to
      have ruptured uterus caused by obstructed labor secondary to interlocking of
      twins. An extremely rare type of conjoined twins (with two heads, two necks, four
      upper extremities, single trunk, two legs) known as Dicephalus tetrabrachius was
      delivered Clinical presentation of the case is presented The case is discussed
      after review of literatures is made from Ethiopia and other countries.

PMID- 18326351
TI  - Congenital epulis.

PMID- 18326352
TI  - Tb drug resistance: is it really a threat to Africa?
AB  - In most of the world and particularly in Eastern Europe, China and India, drug
      resistance is increasingly seen as a major threat to tuberculosis (TB) control
      and even to public health and health security. What about in Africa? The
      conditions for creation of drug resistance exist in most, if not all, African
      countries, as a result of underinvestment in basic TB control, poor management of
      anti-TB drugs and virtual absence of infection control measures. The severity of
      drug resistance is increasing--following outbreaks all over the world of multi
      drug resistant TB (MDR) in the 1990's, extensive drug resistant (XDR) TB has now
      been found in 37 countries, including South Africa. (MDR is, in essence,
      resistance to the most powerful first-line drugs, and XDR-TB is TB resistant to
      the most powerful second-line drugs as well.) Worse still, the impact of XDR-TB
      is magnified among those with HIV infection, giving rise to a remarkably high
      mortality, and exposing significant weaknesses in both HIV and TB control. In
      particular, the lack of laboratories capable of carrying out culture and drug
      susceptibility testing severely limits the capacity of countries even to detect
      the problem in Africa. This paper analyses the threat of TB drug resistance to
      health and to TB control in Africa, and puts forward measures to diminish this
      threat.

PMID- 18326353
TI  - Magnesium sulphate: a neglected life saving drug in Ethiopia?

PMID- 18326354
TI  - [Contraception: new challenges].

PMID- 18326355
TI  - [Question raised by the limits of viability in extremely preterm infants].
AB  - Recent advances in perinatology allow to take care routinely of extremely preterm
      babies. Medical problems as well as ethical questions raised by initiation and
      withdrawal of intensive care of these infants are discussed here. Successively
      are considered what population is concerned by the so-called limits of viability,
      the long-term results of the medical interventions and the ethical questions
      resulting of them.

PMID- 18326356
TI  - [A contraception adapted to each woman].

PMID- 18326357
TI  - [Physiology of ovulation and mode of action of contraceptive pills].
AB  - Follicular ovulation occurs at most 400 times in a woman's lifetime. This process
      involves enzymatic destruction of the cells surrounding the oocytes, called
      cumulus oophorus. The three different partners in order to obtain normal
      ovulation are the oocytes, the mature follicle containing adequate LH receptors
      and the hormones, especially progesterone and the preovulatory LH surge.
      Contraceptive pills available so far contain ethynyl estradiol, in order to
      regulate bleedings. The different progestins in the contraceptive pill exert an
      antigonadotropic effect and therefore inhibit follicular recruitment. As third
      generation progestins exert a stronger antigonadotropic effect than previous
      progestins, the dose of ethynyl estradiol has been lowered in the past 50 years.

PMID- 18326358
TI  - [Hormonal contraceptives].
AB  - Many changes occurred in hormonal contraceptives in the past few years to improve
      benefice/risks balance and get a better tolerance and observance. These changes
      concerned the decrease of steroids doses, changes in estroprogestogen sequence,
      use of less androgenic progestogen and more recently the use of new ways of
      administration with transdermal system, vaginal ring or subdermal contraceptive
      implant to avoid daily use. This article makes a review of hormonal
      contraceptives available in France and benefits of recent innovations.

PMID- 18326359
TI  - [Non hormonal contraception].
AB  - Excluded hormonal contraceptives, there are non hormonal means of contraception.
      Among them, copper intrauterine devices (IUD) are very efficient. Copper IUD are
      the most used contraceptives in France and in the world, even then "false ideas",
      like contraindication to non steroidal anti-inflammatory drugs or higher risk of
      tubal infertility, have tarnished its reputation. The other non hormonal
      contraceptives, less effectiveness, include first, the male and female condoms
      which are the only efficient means to prevent sexually transmitted infections and
      then the "local" contraceptives like spermicides, diaphragms and cervical caps.
      The effectiveness of these methods depends primarily on their correct use (which
      requires a careful training). Then these "local" means are acceptable
      contraceptive methods only for specific use or for very motivated women.

PMID- 18326360
TI  - [First visit for contraception].
AB  - The first visit for contraception essentially aims at listening and providing
      information and counseling. The choice of the contraceptive methods takes into
      account the contra-indications of the method as well as the patient personnel
      history, the type of demand, the needs and the fears. For young women, the most
      preferred choice is the combined pills, very effective and with minima sides
      effects but other methods (IUD, barrier methods) should be kept in mind.
      Observance requires proper information and reassurance on side effects
      particularly on menstruation disorders (amenorrhea, spotting) to avoid drop out.

PMID- 18326361
TI  - [Emergency contraception].
AB  - Emergency contraception is indicated when no birth control is used or in case of
      contraception failure. To day, two methods of emergency contraception are
      available. The hormonal method consists in taking a tablet of levonorgestrel 1.5
      mg (NorLevo), as soon as possible following the contraceptive failure since its
      efficiency decreases rapidly as time goes by. No contraindication is associated
      with this contraceptive; however, it cannot be used as a regular contraception
      method since it is not 100% efficient (from 95.5 to 89% according to the
      authors). Apparently, this contraceptive acts by delaying ovulation. Mechanical
      contraceptives, such as intra-uterine devices, are extremely efficient (99.5%)
      and can be used up to 5 days after the estimated ovulation date. However, surveys
      conducted by the Inserm have revealed that in France, women are not aware of or
      lack of knowledge about emergency contraception and have many misconceptions.
      Moreover, many of them do not use emergency contraception since they do not feel
      concerned by the risk of pregnancy following contraception failure.

PMID- 18326362
TI  - [What to do when you forget to take the birth control pill].

PMID- 18326363
TI  - [Difficult contraceptions].
AB  - Choosing a contraceptive method is difficult in women with a disease or
      presenting specific risk factors. The possible life-threatening effects of the
      contraceptive on the disease and the possible drug interactions should be taken
      into consideration. In this article, we will address the issues faced in patients
      with neurological diseases (epilepsy, brain tumor, migraine, prolactin-secreting
      adenoma), vascular diseases (venous thrombosis, biological thrombophilia,
      arterial diseases), metabolic disorders (obesity, dyslipemias, diabetes), uterine
      diseases (fibromas, endometriosis), renal failure, benign and malignant breast
      diseases as well as in HIV-positive women. Unfortunately, the available
      scientific data are insufficient for several of these conditions, which leads to
      a non-validated management. Controlled studies are needed to improve knowledge.

PMID- 18326364
TI  - [Postpartum and postabortion contraception].

PMID- 18326365
TI  - [Emergency contraception].

PMID- 18326366
TI  - [2008: time for primary care groups? 1. The demographic question].

PMID- 18326367
TI  - [Hemoptysis. Diagnostic orientation].

PMID- 18326368
TI  - [Digestive parasitosis: giardiasis, taeniasis, ascariasis, enterobiasis,
      amoebiasis, hydatidosis].

PMID- 18326369
TI  - [Mood disorders. Bipolar psychosis].

PMID- 18326370
TI  - [Epistaxis (with treatment). Diagnostic orientation].

PMID- 18326371
TI  - [Pharmacologic and nonpharmacologic treatments of pain. Regulatory plan for
      treatment prescription and recommendations].

PMID- 18326372
TI  - [Short history of the hospital of Tonnerre].

PMID- 18326373
TI  - The Campbell Commission: a missed opportunity.

PMID- 18326374
TI  - Public reporting: one piece of the quality improvement puzzle.

PMID- 18326375
TI  - Hospital admissions via the emergency department: implications for planning and
      patient flow.
AB  - In summary, there are important differences among patients admitted via the ED
      versus those admitted via other means in terms of both utilization and patient
      characteristics. When compared with patients admitted via other means, patients
      admitted via the ED are more likely to fall into the medical patient group, to be
      older and to have more complex and more diseases or health conditions. Medical
      patients admitted via the ED are more likely to become ALC patients than are
      other types of patients. As hospitals, health regions and policy makers focus on
      improving patient flow through Canada's EDs, it is important to consider the
      volume and characteristics of the patient population admitted via the ED.

PMID- 18326376
TI  - Choices and tradeoffs: decreasing costs or improving hospital mortality rates.

PMID- 18326377
TI  - In conversation with Ben Chan. Interview by Ken Tremblay.

PMID- 18326378
TI  - Contemporary disease management in Quebec.
AB  - Health or disease management (DM) has emerged as a promising solution to improve
      the quality of healthcare and patient outcomes in a cost-efficient way. This
      solution is particularly relevant in the care of our increasing, and aging,
      patient populations with multiple chronic diseases. This article reviews the
      recent history and current status of DM in the province of Quebec and summarizes
      its evolving perspectives and future prospects. Most DM projects in Quebec have
      developed from a public-private partnership, and they have addressed several
      disease states. The results of completed programs confirmed the presence of care
      gaps--the differences between best and usual care in several disease states. They
      also identified process changes leading to improved practices and enhanced
      professional satisfaction among stakeholders. Priorities identified for further
      research include increased knowledge of the underlying causes of care gaps and
      greater concentration on the measurement of clinical, humanistic and fiscal
      outcomes and their causal links to DM structures and processes. Although still
      embryonic in Quebec and Canada, the available evidence suggests that DM
      partnerships are practical and functional vehicles to expedite knowledge creation
      and transfer in the care of whole populations of patients. Future projects offer
      the promise of updated knowledge and continuously improved care and outcomes.

PMID- 18326379
TI  - Chronic disease prevention and management: implications for health human
      resources in 2020.
AB  - Through improved screening, detection, better and more targeted therapies and the
      uptake of evidence-based treatment guidelines, cancers are becoming chronic
      diseases. However, this good-news story has implications for human resource
      planning and resource allocation. Population-based chronic disease management is
      a necessary approach to deal with the growing burden of chronic disease in
      Canada. In this model, an interdisciplinary team works with and educates the
      patient to monitor symptoms, modify behaviours and self-manage the disease
      between acute episodes. In addition, the community as a whole is more attuned to
      disease prevention and risk factor management. Trusted, high-quality evidence
      based protocols and healthy public policies that have an impact on the entire
      population are needed to minimize the harmful effects of chronic disease.
      Assuming we can overcome the challenges in recruitment, training and new role
      development, enlightened healthcare teams and community members will work
      together to maintain the population's health and wellness and to reduce the
      incidence and burden of chronic disease in Ontario.

PMID- 18326380
TI  - Organizing healthcare delivery systems for persons with ongoing care needs and
      their families: a best practices framework.
AB  - How systems of care delivery are structured can have a major impact on their
      relative efficiency and on the quality of care provided to individuals. As the
      population continues to age, as more people are able to continue to live with
      disabilities or chronic conditions, and as demands continue from consumers and
      lobby groups to allow individuals to be more fully integrated into customary
      Canadian life, pressures to deal with the needs of persons with ongoing care
      requirements will only continue to mount.

PMID- 18326381
TI  - The impact of Ontario's end-of-life care strategy on end-of-life care in the
      community.
AB  - This article describes the impacts of the Ministry of Health and Long-Term Care's
      End-of-Life Care Strategy on the quality of end-of-life (EOL) care services
      delivered by home care providers across the province of Ontario. We compared key
      home care services one year before the strategy's implementation with those one
      year after. In addition, we conducted a qualitative survey of all community care
      access centres, the main providers of home care, and nearly all EOL Care Network
      directors to assess improvements to EOL care at the system and client level.
      Results showed that the number of clients of EOL care served increased by 3,537
      over the baseline year. Moreover, the total number of nursing visits, shift
      nursing hours and personal support hours increased by 26%, 31% and 47%,
      respectively, compared with the baseline year. The qualitative analysis indicated
      that increased collaborations and communication have enhanced integration,
      coordination and consistency of EOL care. Anecdotally, clients and families feel
      more supported navigating the healthcare system, and more of their wishes are
      being met. The strategy appeared to improve EOL care on multiple levels. However,
      several barriers and challenges remain. Further investments and research are
      needed to achieve reliable quality EOL care for all Ontarians.

PMID- 18326382
TI  - The Guidelines International Network: translating best evidence into best
      practice around the globe.
AB  - From August 22 to 25, 2007, the Guidelines International Network (G-I-N) met in
      Toronto for its first North American conference. The theme of G-I-N 2007 was
      collaboration as it pertains to clinical practice guidelines (CPGs). Delegates
      from four continents approached the theme from many directions, including
      development, assessment, translation, implementation and evaluation.

PMID- 18326383
TI  - Improving prescribing, improving health.
AB  - Prescription drugs play an essential and growing role in Canada's healthcare
      system and the health of Canadians. But some drugs are not used correctly
      (misuse), used too frequently (overuse) or not used nearly enough (underuse),
      resulting in missed health benefits, harm to individual Canadians and unnecessary
      costs. In this article, we highlight lessons learned from the Health Council of
      Canada's synthesis of evidence and a recent symposium regarding what works to
      improve the appropriateness of prescribing.

PMID- 18326384
TI  - Radiation dose in interventional cardiology procedures: urgent need for
      monitoring dose and establishing diagnostic reference levels.
AB  - The use of fluoroscopy in interventional cardiology procedures may expose
      patients to levels of radiation that manifest in unintended outcomes. Such
      outcomes may include skin injury and cancer. Currently, there is limited
      understanding of the magnitude of dose administered in an individual procedure.
      Canada does not have a formal policy for monitoring and recording the radiation
      dose administered to patients. This article reviews existing American, European
      and international policies for both monitoring administered radiation dose and
      patient follow-up. As a subsequent focus, this article presents the process for
      setting benchmarks for optimizing administered dose in the Hamilton Health
      Sciences Heart Investigation Unit.

PMID- 18326385
TI  - Patient education as a strategy for provider education and engagement: a case
      study using myJointReplacement.ca.
AB  - MyJointReplacement.ca was initiated to integrate patient and provider
      perspectives with the evidence on joint replacement care into a patient education
      website to promote consistency in practice. The project's leadership ensured that
      the project fit into a larger system change initiative. The literature was
      reviewed and a qualitative study determined patient perspectives on what
      information was required. Findings were discussed with providers and integrated
      into the website. The site hosts nearly 1,700 one-hour sessions monthly. In a
      survey of 50 providers, 40 providers (80%) indicated that they would align their
      practice with the findings, and 45% (90%) believed that the site reflected best
      practice. Over 80% (n = 70) of patients surveyed indicated that the site
      increased their knowledge. It was concluded that developing a patient education
      website is an innovative approach to provider education if supported by
      leadership that can integrate the initiative into a broader context.

PMID- 18326386
TI  - Who will demand access to their personal health record? A focus on the users of
      health services and what they want.
AB  - 3C have a constant need to manage their own personal healthcare. This requires
      managing information related to their conditions. Given that the nature of
      healthcare is information intensive, effective management requires much more than
      simply providing patients with access to their electronic health record within a
      hospital-based system. This practice has been followed with little ongoing
      success. 3C will need a health recording system specifically designed and
      implemented for them, with essential decision-support capabilities built in.
      Furthermore, while non-3C may experience peaks and valleys of increased
      consumption of healthcare services, which alter their contextual environment, 3C
      are constantly engaged through either the consumption of information to improve
      self-management or the consumption of health services to treat the underlying
      condition and all of the associated comorbidities. As a result, 3C will not only
      demand information within effectively designed PHRs, but they will do so in ways
      and in frequencies that we have not yet imagined. This has been the experience
      from many industries once the primary end-users have been empowered. We conclude
      with a single yet most important recommendation: that the healthcare system
      recognize 3C as powerful active participants with the ability to drive change and
      the adoption of PHRs. Opportunities must be provided to involve 3C in system
      design, testing and development.

PMID- 18326387
TI  - From policy to practice: assessing the impact of staging policies for recording
      cancer stage across Canada.
AB  - In 1998, a survey of all hospitals in Canada by the National Cancer Institute
      (NCI) of Canada found that only 17% reported that stage was routinely recorded.
      Closely following the methodology of the 1998 study, an online questionnaire was
      sent to the chief executive officer of 201 institutions in Canada. Since the
      study in 1998, it was found that the staging rate in Canada has significantly
      increased from 17 to 36%. The implementation of a staging policy has had a
      significant impact on the practices of recording stage, but further policy
      initiatives, education and communication are required to improve institutional
      staging practices.

PMID- 18326388
TI  - Web 2.0 and chronic illness: new horizons, new opportunities.
AB  - "Web 2.0" heralds a breakthrough opportunity for empowering healthcare consumers
      of all types, and especially for those suffering from different forms of chronic
      illness. As the author shows using some data gathered from a popular social
      networking website--MySpace.com--this opportunity may be greatest for heavily
      stigmatized chronic health issues, such as obesity and mental illness.

PMID- 18326389
TI  - Electronic health records and patient safety: what lessons can Canada learn from
      the experience of others?
AB  - It is recognized that the Electronic Health Record (EHR) has significant
      potential to improve patient safety in Canada. However, the scientific evidence
      connecting EHRs to improvements in patient safety is incomplete. Additionally,
      international experience has demonstrated that EHRs trigger profound cultural and
      organizational changes in healthcare delivery. Consequently, Canada has a unique
      opportunity to learn from these experiences.

PMID- 18326390
TI  - Ambulatory electronic medical records for large practices.
AB  - In summary, providers and vendors alike have made great strides in EMR adoption
      among physicians in large-scale ambulatory practices. However, there is still
      work to be done in the areas of physician use, adoption obstacles, workflow and
      physician satisfaction. As vendors continue to enhance EMR technology, advance
      workflow and solve challenges with integration and physician acceptance, adoption
      will grow and providers will be even closer to their specific efficiency, safety
      and effectiveness goals.

PMID- 18326391
TI  - Millennium Development Goals (MDGs): a global policy paradox.
AB  - Health status is connected with factors such as the environment, trade, economic
      growth and national security. Due to these close associations, health has emerged
      as a mediating factor inherent to a nation's prospect for human development.

PMID- 18326392
TI  - Confidentiality and privacy in health care from the patient's perspective: does
      HIPAA help?

PMID- 18326393
TI  - Schroeder Lecture. The role of science in health policy decision-making: the case
      of emergency contraception.

PMID- 18326394
TI  - The link between fast food and the obesity epidemic.
AB  - OBESITY: Over thirty percent of adults are obese and over fifteen percent of
      children are considered obese. RESEARCH STUDY: Fat, sugar, and cholesterol have
      addictive qualities similar to the drug nicotine.

PMID- 18326395
TI  - The Patient Safety and Quality Improvement Act of 2005: who should pay for
      improved outcomes?

PMID- 18326396
TI  - An EPICC oversight: why the current battle for access to contraception will not
      help reduce unintended pregnancy in the U.S.

PMID- 18326397
TI  - Muddying the waters: how the Supreme Court's decision in Merck v. Integra fails
      to resolve problems of judicial interpretation of 35 U.S.C. Section 271(E)(1),
      the "safe harbor" provision of the Hatch-Waxman Act.

PMID- 18326398
TI  - Closing the loopholes in the regulation of medical devices: the need for Congress
      to reevaluate medical device regulation.

PMID- 18326399
TI  - [Genetics. Foreword].

PMID- 18326400
TI  - [Genetics of craniofacial development].
AB  - Congenital craniofacial malformations vary widely in both expression and gravity.
      To understand congenital craniofacial malformations, knowledge of embryonic
      development is of essential importance. Craniosynostosis has its origin in the
      failure of suture development between 2 bone centres or in early closure of the
      suture by bone centre tissue fusion. Hereditary craniosynostosis phenotypes
      predominantly arise by autosomal dominant inheritance. So far, the majority of
      mutations have been found in fibroblast growth-factor receptor genes (FGFR
      genes). Different phenotypes are not primarily created by disparities of the
      receptors, but particularly by tissue-specific expressions.

PMID- 18326401
TI  - [Embryonic odontogenesis in vertebrates. A mini-review].
AB  - Although the molecular cascades that control craniofacial development are still
      largely unknown, the generation of mutant animal models and the identification of
      gene mutations that cause human craniofacial syndromes have recently given
      significant insight into how the unique structure of the head develops.
      Craniofacial structures are formed from the prechordal mesoderm, the craniofacial
      ectoderm as well as the neural crest cells which develop on the dorsal side of
      the neural tube. Normal craniofacial morphology as well as normal (in number and
      in morphology) tooth organs develop as a consequence of complex interactions
      between these embryonic tissues. A series of inductive and reciprocal signals
      between the epithelium and mesenchyme determine the growth, the form and the
      ultimate differentiation of tissues and organs. Genetic research has shown the
      involvement of numerous developmental genes encoding a variety of transcription
      factors, growth factors and receptors. Mutations have been associated with, among
      others, non-syndromal forms of cleft palate, agenesis of tooth organs and
      abnormalities in the cranial bones.

PMID- 18326402
TI  - [Genetics and caries].
AB  - Caries is a multi-factorial disease, primarily caused by acids. Acids are
      produced by bacteria which ferment sugar. The aetiology and progress of caries
      are influenced by life-style and environmental factors, as well as congenital
      components. Based on, among other things, research concerning twins, the
      literature suggests that there are hereditary components of caries and life-style
      and environmental components. With the unravelling of the human genome, it is
      more easy to study individual genes in relation to the caries process. Because of
      its multifactorial nature, one has to realise that there is only a beginning of
      understanding the caries processes at molecular level.

PMID- 18326403
TI  - [Genetics and periodontitis].
AB  - Periodontitis is a complex, multifactorial disease and the susceptibility is
      genetically determined. In the last decade a multitude of research projects on
      genotyping of patients and controls in search of putative genetic risk factors
      has been performed. The disease (phenotype) however is also dependent on the
      presence of environmental and lifestyle factors, and their interaction with the
      various genes. Many candidate genes have been proposed and studied in relation to
      periodontitis. Most of the studied candidate genes code for proteins that play a
      role in the innate immune system. Some variants of candidate genes (gene
      polymorphisms) in the IL1 gene cluster and the FcgammaR genes are possibly
      associated with periodontitis. However till today there is no strong evidence for
      target genes and gene polymorphisms that play a key role in the susceptibility to
      and severity of periodontitis. Therefore genetic testing for periodontitis is
      currently not indicated.

PMID- 18326404
TI  - [Microbial genetics. New possibilities for the prevention and treatment of (oral)
      infections].
AB  - New insights in the microbial genetics of pathogenic oral micro-organisms and the
      development of a new array of molecular genetic techniques together have led to
      alternative strategies in the development of antimicrobial agents. In this
      article the importance of insights in microbial molecular biology for the
      prevention and treatment of (oral) infectious diseases is illustrated. Following
      the introduction of relevant terminology, the role of microbial genetics in
      developing of target-based anti-microbial drugs for prevention and treatment of
      (oral) infections is discussed. Subsequently, the impact of microbial genetics on
      vaccine development and several, mainly still experimental, prevention strategies
      are discussed.

PMID- 18326405
TI  - [Heridity of non-syndromal orofacial clefts].
AB  - Non-syndromal orofacial clefts are congenital anomalies with a high incidence of
      heterogeneous origin. The condition is usually multifactorially determined,
      caused by interaction between multiple genetic and environmental factors. So far,
      only a few causal factors have been identified. Even in genetically identical
      individuals like monozygotic twins, the orofacial cleft is usually not fully
      concordant. As an illustration of non-syndromal orofacial clefts, monozygotic
      twin brothers with orofacial clefts which are not fully concordant are presented.

PMID- 18326406
TI  - [Think bigger].

PMID- 18326407
TI  - [Saliva and intensity modulated radiotherapy].
AB  - A dry mouth (xerostomia) is a serious side effect for head and neck cancer
      patients treated with radiotherapy. The degree of xerostomia is dependent on the
      dosage in the parotid glands. New, advanced radiation techniques, such as
      intensity-modulated radiotherapy, can reduce the dosage in the parotid glands,
      resulting in a significant improvement in the functioning of these glands by
      comparison with conventional radiation techniques.

PMID- 18326408
TI  - [Differential diagnosis in patients with suspected anoxic-ischaemic coma].
AB  - Three case studies illustrate that suspected anoxic-ischaemic coma often requires
      careful differential diagnosis to detect treatable conditions. A 47-year-old man
      underwent cardiopulmonary resuscitation for ventricular fibrillation caused by
      myocardial ischaemia. He exhibited rhythmic eyelid movements while in a coma.
      Epilepsy was suspected, and the patient regained consciousness after being
      treated with antiepileptic drugs. A 34-year-old man underwent cardiopulmonary
      resuscitation for multiple episodes of ventricular fibrillation. Treatment was
      directed toward myocardial ischaemia and included anticoagulants. The patient had
      bilateral, fixed dilated pupils. A CT of the brain showed traumatic contrecoup
      haemorrhage in the left temporal lobe with signs of transtentorial herniation.
      The patient died. A 74-year-old woman was found unconscious at home. An ECG
      performed by the paramedics showed ST segment elevation in the precordial leads.
      Anoxic-ischaemic coma following cardiac arrest was suspected. However, a coronary
      angiogram was normal and a CT of the brain revealed subarachnoid haemorrhage
      caused by a ruptured intracranial aneurysm. She recovered after cranial surgery.

PMID- 18326409
TI  - [Elimination of all trans fatty acids].
AB  - At the start of the 20th century, the production of trans fatty acids was
      originally largely driven by the increasing demand for margarine. The two Dutch
      margarine firms Van den Bergh and Jurgens played an important role in this early
      development. In the early 1990s it was shown that trans fatty acids increase the
      risk of heart disease. Unilever, the successor to Van den Bergh and Jurgens, then
      took the lead in eliminating trans fatty acids from retail foods worldwide. As a
      result, intake in The Netherlands fell from 15 g per day in 1980 to 3 g per day
      in 2003. Dairy products and meat are now the major source of trans fatty acids.
      The effects on health of these ruminant trans fatty acids are unclear. There are
      three lessons to be learned from the rise and fall of trans fatty acids. First, a
      history of safe use does not guarantee safety of food components, because routine
      surveillance will fail to detect adverse effects on common illnesses with long
      incubation periods. Second, it shows that it is more effective and easier to
      change the composition of foods than to change consumer behaviour. And third,
      governments can have a major impact on consumers' health by mandating the use of
      healthier food ingredients.

PMID- 18326410
TI  - [Prognosis for patients in a coma following cardiopulmonary resuscitation].
AB  - Most patients with post-anoxic coma after resuscitation have a poor prognosis.
      Reliable prediction of poor outcomes (death or vegetative state after 1 month;
      death, vegetative state or severe disability after at least 6 months) at an early
      stage is important for both family members and treating physicians. Poor outcome
      can be predicted with 100% reliability in the first 3 days after resuscitation in
      about 80% of patients using pupillary and corneal reflexes and motor response
      from the neurological examination, cortical responses from somatosensory evoked
      potentials and EEG. The predictive value of a status epilepticus or serum levels
      of neuron-specific enolase is uncertain at this time. In contrast to poor
      outcomes, good neurological recovery cannot be predicted reliably at this time.

PMID- 18326411
TI  - [Induced mild hypothermia to limit neurological damage after resuscitation].
AB  - Despite improvements in resuscitation techniques, the prognosis for patients who
      experience cardiac arrest outside of a hospital remains relatively poor. This is
      mainly due to brain damage that occurs as a result of global cerebral ischaemia.
      In 2002, two prospective randomised multicentre studies demonstrated that induced
      mild hypothermia can increase the chance of good neurologic recovery after out-of
      hospital cardiac arrest by at least 40%. For this reason, induced mild
      hypothermia (32-34 degrees C) was included in the resuscitation guidelines
      developed by the International Liaison Committee on Resuscitation. Mild
      hypothermia is relatively easy to apply and has few complications. Compared with
      normothermia, induced mild hypothermia increases the chance of good neurological
      recovery by 1.7-fold. A safe and effective method to induce mild hypothermia is
      the infusion of cold fluids during sedation and mechanical ventilation. Cardiac
      function, renal function and electrolytes must be monitored closely during
      induced mild hypothermia. Given the potentially deleterious effects of rapid
      rewarming, a maximal rewarming rate of 0.5 degrees C per hour is recommended.

PMID- 18326412
TI  - [Diagnostic image (360). A woman with lowered consciousness].
AB  - A 42-year-old woman presented with lowered consciousness, ataxia and
      ophthalmoplegia; MRI of the brain revealed abnormalities compatible with Wernicke
      encephalopathy (thiamine deficiency).

PMID- 18326413
TI  - [From the Cochrane Library: increased walking distance through supervised
      exercise therapy in patients with intermittent claudication].
AB  - Intermittent claudication is the most important symptom of peripheral arterial
      disease. Walking is the main treatment for intermittent claudication and is
      usually prescribed as a single recommendation to 'go home and walk'. A recent
      Cochrane systematic review of 7 randomised trials and 1 controlled trial compared
      a supervised walking regimen with non-supervised exercise therapy. Supervised
      exercise therapy showed statistically significant benefits compared with non
      supervised exercise therapy. Further research is needed to determine the clinical
      relevance of this difference, with a focus on quality of life. Long-term results
      with supervised exercise therapy should be studied in future trials.

PMID- 18326414
TI  - [Overweight and obesity in preschool children (0-4 years): behaviour and views of
      parents].
AB  - OBJECTIVE: Description of unhealthy behaviour and views regarding nutrition,
      physical exercise and education in families with young children, in relation to
      specific groups with a high risk of overweight. DESIGN: Cross-sectional study.
      METHOD: In wellbaby clinics for infants and toddlers in various sites in The
      Netherlands 534 parents were requested to fill in questionnaires on nutrition,
      physical exercise and education. Enquiry into background characteristics took
      place and several hypotheses were tested. Using a bivariate and multivariate
      analysis each hypothesis was examined with regard to linkage of the answers to
      specific high-risk groups. RESULTS: 73% (390 parents) responded. Overweight was
      found in 15% of the 2-4-year-olds, this included 3.7% with obesity. Relatively
      often, parents held views and showed behaviour characteristic of an unhealthy
      lifestyle for young children. For example, approximately 1 out of 7 families was
      not used to having breakfast. 43% of the respondents considered sweetened milk
      products approprite substitutes for milk and 39% of the children always had soft
      drinks at their disposal. One fifth of the parents indicated that they did not
      have enough time to go out with their child. Approximately 1 out of 10 toddlers
      aged 2-4 years had a TV in their own room; 22% were allowed to determine whether
      they wanted to watch TV or not and 9% were allowed to decide how long they
      watched. Such specific high-risk behaviour was seen in particular in families
      with non-western mothers, mothers with a low level of education or mothers living
      on social security. Regular use of child care or a nursery seemed to have some
      protective effect. CONCLUSION: In families with children aged 0-4 years,
      behaviour patterns related to overweight at a later age were frequently observed.
      In view of the increased incidence of overweight and obesity in young children,
      initiation of research aimed at optimisation of education is warranted, which
      should include special attention for the behaviour of parents with regard to 5
      spearheads: breast-feeding, more outside play and more physical exercise, a
      regular wholesome breakfast, less consumption of sweetened drinks and less TV and
      computer use. Implementation of interventions in young age groups is able to
      prevent the development of unhealthy lifestyle and childrearing styles.

PMID- 18326415
TI  - [Subarachnoid haemorrhage presenting clinically as circulatory arrest in acute
      myocardial infarction].
AB  - A 59-year-old woman and a 41-year-old man were both brought to the Cardiac
      Emergency Clinic with circulatory arrest on the basis ofpulseless electrical
      activity. The first patient had had no prodromal symptoms and the second patient
      had visited his general practitioner 2 weeks earlier because of pain in the head
      and neck. In both patients, electrocardiography and echocardiography suggested
      acute myocardial infarction. However, both patients proved to be suffering from a
      subarachnoid haemorrhage (SAH) and both died. One-third ofthe patients with SAH
      are comatose at presentation. Cardiac manifestations such as ECG-abnormalities,
      cardiac arrhythmias, cardiopulmonary arrest, elevated troponin values, and signs
      of left ventricular dysfunction are common. These findings can be misleading and
      may have catastrophic consequences if anticoagulant therapy is initiated because
      of a presumed myocardial infarction. Low-threshold CT-scanning of the brain is
      therefore advised for patients who remain comatose after resuscitation for
      cardiac arrest in the presence of an atypical anamnesis.

PMID- 18326416
TI  - [Cardiac symptoms due to pectus excavatum in a man over the age of 55].
AB  - A healthy 59-year-old man, a retired general practitioner, suffered from
      increasing palpitations, fatigue and postural dyspnoea: bending over led to a
      significant increase in his shortness of breath. Cardiological and pulmonological
      examination, performed at regular intervals, showed occasional supraventricular
      arrhythmia and nodal tachycardia but did not yield a satisfactory explanation for
      the symptoms. In the years that followed, the physical impairment became a
      considerable handicap. Finally, the patient himself suggested a possible
      explanation on the basis of an Internet search: his pectus excavatum. A
      literature search confirmed this hypothesis. A lateral chest X-ray in bending
      position and a CT-scan of the chest revealed compression of the heart by the
      sternum. Ten years after the onset of symptoms, a modified Ravitch operation
      finally brought nearly complete recovery.

PMID- 18326417
TI  - [Stupid at the slaughtering table].

PMID- 18326418
TI  - [Chest pain due to a panic disorder: the significance of a multidisciplinary
      approach].

PMID- 18326419
TI  - [Young epidemiologists: oversectorialized and without decisional power].

PMID- 18326420
TI  - [Prevention and public health: themes for further discussion].

PMID- 18326421
TI  - [Enrolment and follow-up of a birth cohort in Rome].
AB  - OBJECTIVE: Longitudinal studies on cohorts of babies enrolled at birth are
      ongoing in Europe. On the basis of these experiences, a birth cohort study should
      be implemented in Italy at a national level. A pilot study is ongoing in Rome,
      from which we report data on adherence at recruitment and follow-up. DESIGN:
      Prospective cohort study. SETTING: the birth cohort was enrolled between June
      2003 and October 2004, in two hospital ofRome in the district ofthe Local Health
      Unit RME. PARTICIPANTS: we enrolled children of women older than 18 years,
      Italian citizens and residents in the Local Health Unit RME. MAIN OUTCOME
      MEASURES: Baseline characteristics of enrolled women were compared with those of
      refusals, and characteristics of children with a complete follow-up with those
      lost at follow-up. Prevalence Rate ratio (PR) and the relative 95% confidence
      interval were calculated. RESULTS: The cohort consisted of 704 women (54% of the
      contacted) and 719 children. A low level of instruction (PR 2.84), and a
      caesarean delivery (OR 1.41) were significantly associated with the refusal.
      After the enrolment 25 children were lost, 117 were partially followed-up and 577
      had a complete follow-up until the 15 month visit. Mothers of children lost at
      follow-up were less instructed (PR 1.69) and smoked during pregnancy (PR 1.57).
      CONCLUSIONS: During the enrolment and the follow-up of a birth cohort greater
      efforts must be done to avoid selection for the socioeconomic level of the
      family. Keeping a high response rate to follow-up is the only way to ensure a
      good level of internal validity.

PMID- 18326422
TI  - [Malignant mesothelioma in the Veneto Region (north-east of Italy), 1988-2002:
      incidence, geographical analysis, trends and comparison with mortality].
AB  - OBJECTIVE: The study assesses incidence and trend of malignant mesothelioma (MM),
      and mortality from primary pleural tumour (PPT) among residents of the Veneto
      region (North-east of Italy 4,450,000 inhabitants at the last census). The study
      also aims at identifying areas at high risk, by applying geographical analysis
      techniques. METHOD: The results have been obtained through the activity ofa
      Mesothelioma Registry, established in 2001, thus collecting largely retrospective
      data. Incidence and trends are estimated on MM diagnosed between 1988 and 2002 by
      means of histological or cytological techniques. Deaths from PPT are derived
      through the availability of mortality records for the period 1988-1999 (latest
      year available). Direct age-standardization was applied to provincial rates (7
      provinces), whereas standardized mortality and incidence ratios according to
      Kernel estimates and spatial scan statistics have been used to identify clusters
      at the municipality level (581 municipalities). RESULTS AND CONCLUSIONS: the
      incidence of MM in the Veneto region appears similar to that of other northern
      Italian regions (904 new MM cases from 1988 to 2002, 650 among males, 819
      pleural; age-standardized annual incidence rates x 100,000 in the period 1988
      1999): 1.75 (IC 95% 1.59-1.91) among males, based on 460 cases, and 0.67 (IC 95%
      0.57-0.77) among females, based on 196 cases, and displays an increasing trend
      among both genders. Among males incidence doubles during the study period. High
      risks are detected among males in a cluster formed by the city of Venice and
      surrounding municipalities (Standardized Incidence Ratio, SIR, for pleural
      mesothelioma, 1988-1999, 2.94 (p = 0.001) for the cluster based on 110 observed
      cases), and, in addition to Venice, in the province of Padua among females (SIR
      from pleural mesothelioma, 1988-1999, 1.98 (p = 0.001) for the cluster based on
      95 observed cases). Mortality from TPP turns out to be higher than incidence and
      tends to approach incidence in more recent years; this may be explained by the
      increasing application of diagnostic procedures, inclusive of histopathological
      tests, among old patients.

PMID- 18326423
TI  - [Overweight in Italian early adolescents: association with psychosomatic
      symptoms].
AB  - OBJECTIVE: to describe the association between overweight and a number of somatic
      and psychological complaints within a sample of Italian early-adolescents and
      adolescents. DESIGN: the study is apart of the larger transnational study "Health
      Behaviour in School Aged Children" (HBSC), coordinated by the European Office of
      the World Health Organization. The data were collected through self-completed
      questionnaires on forms which had been devised by the international research
      group. The main areas covered in the questionnaire were health and health
      behaviour. SETTING: 151 middle schools and 92 high schools were randomly selected
      from all Italian public and private schools. PARTICIPANTS: the questionnaire was
      filled out by 4386 youngsters (48.4% males). MEASURES: main outcomes which have
      been measured include Body Mass Index, and Psychological and Somatic Complaints.
      RESULTS: the incidence of overweight was correlated to headache (7.8% vs. 4.5%
      non-overweight) and backache (6.4% vs. 2.8%) in males but not in females.
      Overweight males (9.5% vs. 6.5%) and females (22.0% vs. 13.2%) reported feeling
      alow, more often than participants of normal weight. Overweight co-occurred with
      irritability (15.1% vs. 8.0%) only in female participants. CONCLUSION: overweight
      is associated with a poor quality of life in early-adolescence and adolescence.
      The co-occurrence of overweight and psychosomatic symptoms is different in males
      and females.

PMID- 18326424
TI  - [Health impact of ozone in 13 Italian cities].
AB  - OBJECTIVE: to estimate the health impact of ozone in 13 Italian cities over
      200,000 inhabitants and to produce basic elements to permit the reproducibility
      of the study in other urban locations. DESIGN: the following data have been used:
      population data (2001), health data (2001 or from scientific literature),
      environmental data (2002-2004), from urban background monitoring station and
      concentration/response risk coefficients derived from recent metanalyses. The
      indicators SOMO35 and SOMO0 have been used as a proxi of the average exposure to
      calcolate attributable deaths (and years of life lost) and several causes of
      morbility for ozone concentrations over 70 microg/m3. MAIN OUTCOME MEASURE: acute
      mortality for all causes and for cardiovascular mortality, respiratory-related
      hospital admissions in elderly, asthma exacerbation in children and adults, minor
      restricted activity days, lower respiratory symptoms in children. RESULTS: over
      500 (1900) deaths, the 0.6% (2.1%) of total mortality, equivalent to about 6000
      (22,000) years of life lost are attributable to ozone levels over 70 microg/m3 in
      the 13 Italian cities under study. Larger figures, in the order of thousands, are
      attributable to less severe morbidity outcomes. CONCLUSION: The health impact of
      ozone in Italian towns is relevant in terms of acute mortality and morbidity,
      although less severe than PM10 impact. Background ozone levels are increasing.
      Abatement strategies for ozone concentrations should consider the whole summer
      and not only "peak" days and look at policies limiting the concentration of
      precursors produced by traffic sources. Relevant health benefits can be obtained
      also under levels proposed as guidelines in the present environmental
      regulations.

PMID- 18326425
TI  - [Estimating prevalence of diabetes mellitus in a Lazio province, Italy, by
      capture-recapture models].
AB  - OBJECTIVE: to estimate the prevalence of diabetes in a Lazio province, Italy,
      using a record linkage offour patient lists and applying capture-recapture
      techniques. DESIGN AND SETTING: we selected records of individuals living in
      Viterbo province (Lazio region, Italy) from four lists obtained from three
      different health administrative registries in 2004: the hospital discharge
      registry of Lazio region (ICD9-CM code 250, 2488 subjects); the registry of
      outpatient care prescriptions (subjects exempted from medical charge for health
      care related to diabetes, 3582 subjects); subjects with prescriptions of glicate
      haemoglobin (7169 subjects); the registry of exemptions, from medical charge for
      health care of the local health unit of Viterbo province, related to diabetes
      (8529 subjects). A deterministic record linkage using 5 different keys of linkage
      obtained from demographic information, was applied The estimates were derived
      using two capture-recapture techniques: log-linear models and sample-coverage
      approach. RESULTS: Record linkage results using the 5 different keys of linkage
      were similar. Prevalence estimates varied between 63% and 7.8% when all four
      lists were considered and they varied between 5.7% and 6.1% when the glicate
      haemoglobin list was excluded. CONCLUSIONS: Our estimates were slightly higher
      compared to those recently reported in the literature; estimates were
      particularly influenced by the inclusion/exclusion of the haemoglobin glicate
      prescriptions list. Estimates were not influenced either by the key of linkage,
      or by the capture-recapture technique. Health administrative registries can be
      used to estimate the prevalence of diabetes through record linkage and capture
      recapture techniques. This approach leads to a reduction of time and costs
      compared with traditional health surveys.

PMID- 18326426
TI  - [Road accidents in piedmont (Italy): factors affecting mortality among drivers].
AB  - OBJECTIVES: Italy is one of the industrialized countries with the highest
      mortality from road accidents. The mortality index of road accidents in Piemonte
      is one of the highest in Italy. This study assesses the main factors affecting
      the mortality among drivers. DESIGN: Police reports of 95,944 road traffic
      accidents occurred between 1999 and 2004 in Piemonte, involving 178,230 drivers,
      were analysed. Multivariate logistic regression models were used to estimate the
      association of drivers' and accidents' characteristics with mortality among
      drivers. Analyses were stratified for car, truck and two-wheel vehicle drivers.
      RESULTS: Mortality is affected by age and gender. In addition, the main risk
      factors are night-time, extra-urban roads, mountain areas and two wheel vehicles.
      The drivers license penalty point regulation law introduced in Italy on July 2003
      seems to have had a protective effect on mortality during the early months of
      application. CONCLUSIONS: Official data are useful for estimating potential
      determinants of road injuries' outcome. Factors affecting the occurrence of
      accidents are not necessarily predictors of outcome severity. An effective
      prevention policy of frequency of accidents, mortality and disability should be
      based on drivers'safety education, structural interventions, targeted road
      controls and law enforcement.

PMID- 18326427
TI  - [The hazard function].
AB  - In cohort studies the event occurrence is usually described by the incidence rate
      and the survivor function. In comparison with these estimators the plot of the
      hazard function has the advantage to show the variations of the occurrence of the
      event along the period of observation, which often are important to be
      highlighted. Furthermore, when comparing individuals with different
      characteristics, the hazard function is a valuable support to check the
      assumption and to interpret the results of a Cox regression model. This paper
      illustrates the method for estimating the hazard function and an example is given
      from a real case by using the survival data of the breast cancers collected in
      the IMPACT study, aimed to detect the efficacy of the mammographic screening
      program. The relationship between the usual estimators and the hazard function is
      shown and its role in the survival regression modelling is emphasized. In the
      example the estimate of the hazard function allows to point out that the
      mortality rate of breast cancer in the first year after the diagnosis is lower
      than later and that the difference between the hazards of the invited cases and
      those of the not invited cases is approximately constant along the whole l0 years
      follow up, two important remarks both demonstrating the usefulness of the
      application of this function in the analysis of cohort studies.

PMID- 18326428
TI  - [Evaluation of health impact: what is, what can be done, what cannot be done. The
      point of the situation in Italy. Final report, VIS-HIA workshop. Rome, 16
      February 2007].

PMID- 18326429
TI  - [Visceral and cutaneous larva migrans].
AB  - The syndrome of visceral larva migrans was described for the first time in 1952
      by Beaver. He demonstrated that the presence of nematodes larvae, particularly in
      the liver, were those of Toxocara canis and T. cati. Baylisascaris procyonis, the
      common racoon ascarid in the U.S.A. can also cause serious diseases in human.
      Digestive and respiratory clinical symptoms are usually moderate, however severe
      disease resulting from invasion of the myocardium or the brain has been reported.
      A blood hypereosinophilia is usually present the first few years after infection.
      Diagnosis uses serological methods, among them the ELISA test. Ocular larva is
      also possible with in that case, immunological modifications of the aqueous.
      Cutaneous larva migrans characterized by a linear, progressing, serpigenous
      eruption and intense itching is easy to diagnose. Larva migrans is due to dogs,
      cats and horses helminths. Dogs and cats (referred here as pets) now receive
      antihelmintitic treatments and parasites are now in decrease.

PMID- 18326430
TI  - [Kawasaki disease].
AB  - Kawasaki disease (KD) is a febrile systemic vasculitis complicated by coronary
      and peripheral arterial aneurysms in 20% to 35% of untreated patients. It is
      reported as the commonest cause of acquired heart disease in children in
      developed countries, and may be a risk for adult ischaemic heart disease.
      Although KD has been reported all over the world, it is overexpressed among Asian
      populations, especially Japanese people. The annual incidence for 100,000
      children under five years of age is reported to be 8.1 in the United Kingdom,
      17.1 in the United States and 112 in Japan. The principal clinical feature is
      fever, accompanied by extremity changes, polymorphous rash, conjunctival
      injection, changes in lips and oral cavity, and cervical lymphadenopathy. The
      disease pathogenesis is still unknown and several theories have been proposed,
      including the possibility of an infection by a toxin-secreting microorganism and
      of a superantigen-driven process. Despite numerous efforts there is still no
      diagnostic test available for KD, and the diagnosis is based on clinical criteria
      after the exclusion of other diseases presenting with high persistent fever.
      Prompt diagnosis is critical, since the early administration of intravenous
      immunoglobulins and aspirin reduces the rate of coronary abnormalities to less
      than 5% of patients.

PMID- 18326431
TI  - [Dermatofibrosarcoma protuberans].

PMID- 18326432
TI  - [Children's vision. Nearly 100,000 children born in France each year have or will
      have a visual disorder].

PMID- 18326433
TI  - [Children visual functions development].
AB  - Development of vision mainly takes place during the first year of life. Visual
      function isn't restricted to the measurement of visual acuity, but includes
      functions of environment exploration, relative appreciation of objects, control
      of body position and movements organization. Visual function comprises sensorial,
      oculomotor and cognitive elements. Each alteration in visual experience exposes
      to amblyopia inside the period of sensitivity of visual function.

PMID- 18326434
TI  - [Evaluation of the visual disorders of the children].
AB  - The refractive error and the strabismus are the most frequent of the visual
      abnormalities of the children. Without early treatment a high bilateral
      refractive error produces a bilateral amblyopia. The asymmetric refractive error
      and the strabismus can produce unilateral amblyopia when the treatment is delayed
      (glasses for the first and glasses and alternative fixation for the last). The
      early diagnosis is necessary to a preventive action. The search of these
      anomalies is systematic when the family has history of amblyopia or strabismus.
      Sometimes, a strabismus is the first manifestation of a severe visual
      abnormality, the ophthalmologist must quickly examinate all the children with a
      strabismus. The other high abnormalities of visual function (cataracte, glaucoma,
      retinal disease) cause a comportemental dysfunction and/or involve ocular
      modifications. Most of these visual manifestations are diagnosed with an
      attentive easy examination of the children.

PMID- 18326435
TI  - [Infant ametropias and their evolutions (myopia, hyperopia, astigmatism)].
AB  - Infant ametropias are defined as the whole optic caracteristics of the eyeball
      which do not allow a clear vision whithout functional disorder. As the sensorial
      maturity is only achieved at 4 to 5 years, the limits of ametropias are variable
      before that age. The majority of ametropias is constituted as early as 9 months
      and may be detected by a refractive examination under cycloplegia. This situation
      is especially true for hyperopia and astigmatism. The more important are initial
      ametropias the more unchanged they remain. At 9 months, 1 infant out of 5 present
      a non-physiological refraction. From 4 to 5 years, 1 child out of 4 needs a
      refractive correction. Significant myopias are uncommon in infants. They
      generally appear between 7 and 12 years.

PMID- 18326436
TI  - [Child's strabismus].
AB  - Strabismus is characterized by a manifest deviation of the visual axes and
      secondary sensory deteriorations. Strabismus is a frequent affection which
      primarily involved the child, during early life. It is a frequent and severe
      disease (3 to 4% of the French population), if untreated the prognosis is severe
      with the functional loss of deviated eye. The clinical picture, and the prognosis
      depend considerably on the age of onset. Strabismus is always linked to
      amblyopia, explaining the need for a rigorous examination and adapted treatment
      the earliest possible: a collaboration between paediatrician, general
      practitioner, ophthalmologist and orthoptist is essential.

PMID- 18326437
TI  - [Organic causes of bad visual development in the child].
AB  - The eye trouble of organic origin must be diagnosed and treated before the
      installation of an irreversible amblyopia. This early diagnosis rests on the
      observation of the child by his parents but especially on the knowledge of the
      various clinical signs by the general practitioner or the pediatrist. Thus, the
      blindness and the behaviors which is referred to it (leucocorie, strabism,
      nystagmus, or sometimes exophtalmy) must alert the doctor who will then address
      the child towards the ophthalmologist. This one will be able to highlight a
      malformation of the anterior segment, a cataract or glaucoma, an ocular
      inflammation or its after-effects, retinal, orbital or optical ways anomaly. The
      treatment will have to then allow a fast visual rehabilitation in order to treat
      the residual amblyopia as fast as possible. In some cases, it will direct the
      child and his parents towards a structure specialized in order to develop to the
      maximum of the sometimes unexpected visual capacities.

PMID- 18326438
TI  - [The eyes of infants].

PMID- 18326439
TI  - [The physician-administrator partnership].

PMID- 18326440
TI  - [Prescription, monitoring of antithrombotic treatment: 1--antiplatelet agents].

PMID- 18326441
TI  - [Joint pain and effusions].

PMID- 18326442
TI  - [Adjustment disorders and anxiety disorders].

PMID- 18326443
TI  - [Epithelial and melanic skin tumours].

PMID- 18326444
TI  - [Former hospice and museum of medicine in Hautefort].

PMID- 18326445
TI  - Health inequalities among Latinos: what do we know and what can we do?

PMID- 18326446
TI  - Relationship between religious involvement and psychological well-being: a social
      justice perspective.
AB  - Although religion has not been a mainline topic of empirical inquiry in the
      gerontological social work literature, there has been growing recognition in the
      past two decades of the health protective effects of religious involvement on
      both physical and psychological well-being. Depression interferes with both
      individual and social functioning that can lead to persistent problems in healthy
      human development, social relationships, and empowerment in the service of social
      justice. Attention to the salubrious effects of religious involvement on the
      psychological well-being among older U.S. racial and ethnic groups is still in
      its nascent stage. This article examines the relationship among religious
      involvement, private prayer, and depression in a low-income clinical sample of
      230 older U.S.-born and immigrant Latinos. Higher levels of religious attendance
      were associated with lower risk of depressive illness after adjusting for
      selective factors such as physical functioning, stress exposure, and social
      support. Private prayer was not associated with depression. Although immigrants
      were more likely to attend worship services, they reported the same rates of
      depression as their U.S.-born counterparts. The study is an initial step toward
      disentangling the mental health protective effects of religious involvement on
      the health and well-being of older Latinos in the United States.

PMID- 18326447
TI  - A retest of two HIV disclosure theories: the women's story.
AB  - The purpose of this study was to evaluate the applicability of two theories of
      HIV disclosure previously tested with men. Participants included 125 HIV-positive
      women enrolled in a larger, longitudinal study of HIV disclosure and mental
      health. Structural equation modeling was used to analyze the proposed theoretical
      models. The disease progression model contained two single-indicator exogenous
      variables (disease progression) and one endogenous latent variable (disclosure).
      The original consequences model contained two single-indicator exogenous
      variables (disease progression), two single-indicator endogenous variables
      (consequences), and one endogenous latent variable (disclosure). The revised
      consequences model contained two single-indicator exogenous variables
      (consequences) and one endogenous latent variable (disclosure). The results of
      this study support the revised consequences theory and an earlier claim that
      disease progression may not be a direct predictor of HIV disclosure. This
      suggests that women may evaluate the consequences of disclosure to family and
      friends, particularly the reward, before the disclosure occurs.

PMID- 18326448
TI  - Intimate partner violence among midlife and older women: a descriptive analysis
      of women seeking medical services.
AB  - Although intimate partner violence (IPV) may occur throughout a woman's life
      course, there has been a paucity of research on the experiences of victimization
      among midlife and older women. This article examines both the prevalence of IPV
      among a sample of women ages 50 to 64 (N=620), who were recruited at an emergency
      department and primary care clinics in an urban setting, and the associated
      factors for the subsample of these women who reported IPV (n=34). More than 5
      percent of the women reported experiencing some form of abuse by their partners
      within the past two years. Bivariate analyses comparing victims and nonvictims
      indicate that higher proportions of women who reported abuse had received public
      assistance and had a recent history of homelessness. In addition, victims of IPV
      reported higher frequencies of HIV risk factors than did nonvictims, including
      having a partner who insisted on sex without a condom, having sex with a man they
      knew or suspected was an IV drug user, and experiencing symptoms or receiving a
      diagnosis or treatment for a sexually transmitted infection. Significantly higher
      percentages of abused women reported being tested for HIV and being HIV
      seropositive. Implications of the findings for social workers are discussed.

PMID- 18326449
TI  - From the real frontline: the unique contributions of mental health caregivers in
      Canadian foster homes.
AB  - This article reports the findings of a qualitative study on the contribution of
      foster home caregivers for people with serious mental illness. Traditionally,
      social workers have played a key role in the supervision of foster homes. Little
      is known about how the help caregivers provide is similar to, or different from,
      that provided by mental health professionals. Twenty semistructured interviews
      were conducted with caregivers operating foster homes in Montreal, Canada. With
      no preset theoretical framework, data analysis was inductive and ongoing,
      involving the identification of categories and themes. Overall findings revealed
      that caregivers consider themselves the real frontline workers. They claim to be
      available 24 hours a day, seven days a week to combine egalitarian and affective
      relationships with their residents and to provide them with personalized care.
      Caregivers are well positioned to respond immediately to crises. Caregivers also
      believe that their intimate and thorough familiarity with their residents allows
      them to assess residents differently than could social workers. These findings
      have implications for mental health professionals. The combined skills and
      expertise of nonprofessional caregivers and social workers are essential in
      promoting the residents' reintegration into the community.

PMID- 18326450
TI  - Fear of falling and activity avoidance in a national sample of older adults in
      the United States.
AB  - This study assesses the relationship between fear of falling and avoidance of
      nine everyday activities critical to independence among community-dwelling older
      adults in the United States. Secondary data analysis was performed with National
      Survey of Self-Care and Aging interview data from 3474 respondents age 65 years
      or older. Falls were reported by 24 percent of respondents, fear of falling was
      reported by 22 percent of respondents, and both increased with age. Fear of
      falling was the most important factor in predicting activity avoidance among
      older adults; the number of falls experienced increases the impact that fear of
      falling has on activity avoidance. Other factors were as follows: needing help
      with activities of daily living and the number of prescriptions taken.
      Assessments of older individuals should include fear of falling and fall history.
      Reductions in fear of falling and increases in activity level could provide
      significant benefits by helping older adults to maintain functioning and the
      ability to live independently.

PMID- 18326451
TI  - Hospital social workers and indirect trauma exposure: an exploratory study of
      contributing factors.
AB  - This article explores the predictive ability of empathy (measured by the
      Interpersonal Reactivity Index), emotional separation (measured by the
      Maintenance of Emotional Separation Scale), occupational stress (measured by the
      Work-Related Strain Inventory), and social support (measured by the
      Multidimensional Scale of Perceived Social Support) on secondary traumatic stress
      (STS) (measured by the Secondary Traumatic Stress Scale) in hospital social
      workers. This cross-sectional study used a sample of 121 trauma center social
      workers who were predominantly master's-level prepared women with an average of
      15.8 years' experience. Emotional separation and occupational stress were the
      strongest predictors of STS, explaining 49 percent of the variance, which
      suggests that hospital social workers need to be able to emotionally
      differentiate during work with patients and families and manage organizational
      stressors to minimize indirect trauma reactions.

PMID- 18326452
TI  - The Human Genome Project: implications for families.

PMID- 18326453
TI  - Forty-four techniques for empowering older adults living with diabetes.

PMID- 18326454
TI  - Health care reform and accountability.

PMID- 18326455
TI  - With U.S. health care problems rising, new Medicare plans emerge.

PMID- 18326457
TI  - My life with and without a dialysis catheter.

PMID- 18326458
TI  - Changing the course of PD: the Provincial Peritoneal Dialysis Joint Initiative.

PMID- 18326459
TI  - Expanding PD in Ontario: a flawed approach.

PMID- 18326460
TI  - Home hemodialysis in this millennium: the return of the king?

PMID- 18326462
TI  - Infections in dialysis patients.

PMID- 18326463
TI  - An alternative choice for restoring occlusal function.

PMID- 18326464
TI  - Complementary and alternative medicine may reduce costs of care.

PMID- 18326465
TI  - Patients with lupus have lower utilization in HMOs.

PMID- 18326466
TI  - Private payers may reimburse PCPs for coordinating care of seniors with chronic
      illnesses outside office visits.

PMID- 18326467
TI  - Gatekeeping strategies don't influence patient trust.

PMID- 18326468
TI  - [Bluish tongue tumor. Is it malignant?].

PMID- 18326469
TI  - [Uncomplicated urinary tract infections. With the anamnesis it is not done].

PMID- 18326470
TI  - [Complications of liver cirrhosis. Is it still possible to help these patients?].

PMID- 18326471
TI  - [Emergencies in childhood. Bleeding of esophageal varices without liver
      cirrhosis].

PMID- 18326472
TI  - [Unclear lung shadowing in a patient with breast carcinoma. Pneumonia, metastasis
      or...?].

PMID- 18326473
TI  - [Why do patients sue their family physician. The most frequent treatment errors].

PMID- 18326474
TI  - [Antitussives, mucolytics, antibiotics--what do you prescribe for bronchitis?].

PMID- 18326475
TI  - [Infections of the respiratory tract--diagnosis and therapy].

PMID- 18326476
TI  - [Therapy of non-nosocomial pneumonia].

PMID- 18326477
TI  - [Delirium in the old age].

PMID- 18326478
TI  - [Pilonidal sinus].

PMID- 18326479
TI  - [Obscure gastrointestinal bleeding often located in small bowel].

PMID- 18326480
TI  - Quantum-dot-assisted fluorescence resonance energy transfer approach for
      intracellular trafficking of chitosan/DNA complex.
AB  - Fluorescence resonance energy transfer (FRET) was employed to monitor the
      molecular dissociation of a chitosan/DNA complex with different molecular weights
      of chitosan. Chitosan with different molecular weights was complexed with plasmid
      DNA and the complex formation was monitored using dynamic light scattering and a
      gel retardation assay. As the chitosan molecular weight increased, a more
      condensed complex was prepared at various ratios of chitosan to DNA. Plasmid DNA
      and chitosan were separately labeled with quantum dots and Texas red,
      respectively, and the dissociation of the complex was subsequently monitored
      using confocal microscopy and fluorescence spectroscopy. As the chitosan
      molecular weight in the chitosan/DNA complex increased, the Texas red-labeled
      chitosan gradually lost FRET-induced fluorescence light when HEK293 cells
      incubated with chitosan/DNA complex were examined with confocal microscopy. This
      suggests that the dissociation of the chitosan/DNA complex was more significant
      in the high molecular weight chitosan/DNA complex. Fluorescence spectroscopy also
      monitored the molecular dissociation of the chitosan/DNA complex at pH 7.4 and pH
      5.0 and confirmed that the dissociation occurred in acidic environments. This
      finding suggests that the high molecular weight chitosan/DNA complex could easily
      be dissociated in lysosomes compared to a low molecular weight complex.
      Furthermore, the high molecular weight chitosan/DNA complex showed superior
      transfection efficiency in relation to the low molecular weight complex.
      Therefore, it could be concluded that the dissociation of the chitosan/DNA
      complex is a critical event in obtaining the high transfection efficiency of the
      gene carrier/DNA complex.

PMID- 18326481
TI  - [European recommendations for good practice in hemodialysis. Part two].

PMID- 18326482
TI  - Mobilization of endothelial progenitor cells in fracture healing and distraction
      osteogenesis.
AB  - INTRODUCTION: Fracture healing and distraction osteogenesis (DO) are unique
      postnatal bone formation processes, and neovascularization is critically required
      for successful bone regeneration. We investigated endothelial progenitor cell
      (EPC) mobilization during bone regeneration, and the possible contribution of
      EPCs to increased vascularization and new bone formation, especially in DO.
      METHODS: Mouse tibia fracture and rat tibia DO models were used in this study.
      The proportion of EPCs among the peripheral and splenic mononuclear cells (MNCs)
      was determined by examining the endothelial lineage staining characteristics and
      EPC cell surface markers. Messenger RNA expression of molecules related to EPC
      mobilization and homing at the fracture site were analyzed by ribonuclease
      protection assay and reverse-transcription polymerase chain reaction. In the rat
      tibia DO model, we measured blood flow during DO, and determined the distribution
      of ex vivo-expanded and intravenously-infused EPCs. RESULTS: The proportion of
      EPCs among the peripheral and splenic MNCs increased after fracture, peaked on
      post-fracture day 3, and returned to basal levels during the healing period.
      Messenger RNA expression of EPC mobilizing cytokines such as vascular endothelial
      growth factor (VEGF), stem cell factor, monocyte chemoattractant protein-1, and
      stromal cell-derived factor-1, were upregulated at the fracture callus. The
      plasma VEGF levels peaked prior to the increase in the EPC proportion. Adhesion
      molecules involved in EPC homing were expressed at the fracture callus. In the DO
      model, the temporal pattern of the increase in the EPC proportion was similar to
      that in the fracture healing model, but the EPC proportion increased again during
      the distraction and consolidation phases. The distraction gap was relatively
      ischemic during the distraction phase and blood flow increased profusely later in
      the consolidation phase. The number of EPCs homing to the bone regeneration site
      in the DO model correlated with the number of transplanted EPCs in a dose
      dependent manner. CONCLUSIONS: These findings suggest that signals from the bone
      regeneration site mobilize EPCs from the bone marrow into the peripheral
      circulation. Increased EPC mobilization and homing may contribute to
      neovascularization and thus to new bone formation in fracture healing and DO.

PMID- 18326483
TI  - The relationship between domestic violence and animal abuse: an Australian study.
AB  - Several North American studies have found a connection between domestic violence
      and animal abuse. This article reports on the first Australian research to
      examine this connection. A group of 102 women recruited through 24 domestic
      violence services in the state of Victoria and a nondomestic violence comparison
      group (102 women) recruited from the community took part in the study.
      Significantly higher rates of partner pet abuse, partner threats of pet abuse,
      and pet abuse by other family members were found in the violent families compared
      with the nondomestic violence group. As hypothesized, children from the violent
      families were reported by their mothers to have witnessed and committed
      significantly more animal abuse than children from the nonviolent families.
      Logistic regression analyses revealed, for the group as a whole, that a woman
      whose partner had threatened the pets was 5 times more likely to belong to the
      intimate partner violence group.

PMID- 18326484
TI  - Attitudes of Jordanian society toward wife abuse.
AB  - The authors conducted an exploratory study among a convenience sample of 260
      Jordanian men and women, using self-administered open and closed questions to
      examine the participants' approach toward wife abuse. In general, there was high
      awareness of wife abuse and the different types of abuse (mainly physical and
      psychological), a general tendency to oppose wife abuse, a tendency to blame the
      victim for abuse, and a lesser tendency to blame the abuse on the husband,
      marital problems, as well as familial and societal conditions. There was also a
      strong tendency to consider wife abuse a personal and familial issue rather than
      a social and legal problem. Therefore, the preferred method for coping with wife
      abuse and violence was the expectation that the abused wife should change her
      behavior and assume responsibility to change her husband followed by resorting to
      informal agents (family or community or religious figures). Less preferred coping
      methods included confronting the husband and expressing desire to break up or
      separate and resorting to formal agents (social welfare programs, counseling,
      legal system), as a last resort in cases of repeated abuse and severe physical
      violence. The implications of these findings for future research, interventions,
      and policy formulation are discussed.

PMID- 18326485
TI  - Cardiac restricted overexpression of kinase-dead mammalian target of rapamycin
      (mTOR) mutant impairs the mTOR-mediated signaling and cardiac function.
AB  - Mammalian target of rapamycin (mTOR) is a key regulator for cell growth through
      modulating components of the translation machinery. Previously, numerous
      pharmacological studies using rapamycin suggested that mTOR has an important role
      in regulating cardiac hypertrophic growth. To further investigate this
      assumption, we have generated two lines of cardiac specific mTOR transgenic mice,
      kinase-dead (kd) mTOR and constitutively active (ca) mTOR, using alpha-myosin
      heavy chain promoter. alpha-Myosin heavy chain (alphaMHC)-mTORkd mice had a near
      complete inhibition of p70 S6k and 4E-BP1 phosphorylation, whereas alphaMHC
      mTORca had a significant increase in p70 S6k and 4E-BP1 phosphorylation. Although
      the cardiac function of alphaMHC-mTORkd mice was significantly altered, the
      cardiac morphology of these transgenic mice was normal. The cardiac hypertrophic
      growth in response to physiological and pathological stimuli was not different in
      alphaMHC-mTORkd and alphaMHC-mTORca transgenic mice when compared with that of
      nontransgenic littermates. These findings suggest that the mTOR-mediated
      signaling pathway is not essential to cardiac hypertrophic growth but is involved
      in regulating cardiac function. Additional analysis of cardiac responses to
      fasting-refeeding or acute insulin administration indicated that alphaMHC-mTORkd
      mice had a largely impaired physiological response to nutrient energy supply and
      insulin stimulation.

PMID- 18326486
TI  - Integrins uncouple Src-induced morphological and oncogenic transformation.
AB  - Expression of activated mutants of c-Src in epithelial cells can induce
      tumorigenicity. In addition to such oncogenic transformation, the cells undergo a
      dramatic morphological transformation: cell-cell contacts are disrupted,
      spreading on extracellular matrix proteins is suppressed, actin stress fibers and
      focal contacts are lost, and podosomes are formed. We have previously shown that
      integrin alphavbeta3 strongly supports Src-mediated oncogenic transformation
      through an interaction at the beta3 cytoplasmic tail. Our current findings
      demonstrate that this interaction does not affect Src-mediated morphological
      alterations, thus separating oncogenic from morphological transformation.
      Moreover, beta1 and beta3 integrins differently affect the various aspects of Src
      induced morphological transformation. High levels of beta3, but not beta1,
      integrins can prevent Src-induced cell rounding although stress fiber disassembly
      and podosome formation still occur. Studies using chimeric integrin subunits
      demonstrate that this protection requires the beta3 extracellular domain.
      Finally, like tumor formation, podosome assembly occurs independent of beta3
      phosphorylation. Instead, phosphorylation of beta1 is required to suppress Rho
      mediated contractility in order to assemble podosomes. Thus, integrins regulate
      Src-mediated oncogenic transformation and various aspects of morphological
      transformation through dissociable pathways.

PMID- 18326487
TI  - Unc45 activates Hsp90-dependent folding of the myosin motor domain.
AB  - Myosin folding and assembly in striated muscle are mediated by the general
      chaperones Hsc70 and Hsp90 and involve a myosin-specific co-chaperone related to
      the Caenorhabditis elegans gene unc-45. Two unc-45 genes are found in
      vertebrates, a general cell isoform, unc45a, and a striated muscle-specific
      isoform, unc45b. We have investigated the role of both isoforms of mouse Unc45 in
      myosin folding using an in vitro synthesis and folding assay. A smooth muscle
      myosin motor domain (MD) fused to green fluorescent protein (GFP) (MD::GFP) was
      used as substrate, and folding was measured by native gel electrophoresis and
      functional assays. In the absence of Unc45, the MD::GFP chimera folds poorly.
      Addition of either Unc45a or Unc45b dramatically enhances the folding in a
      reaction that is dependent on Hsp90 ATPase activity. Unc45a is more effective
      than Unc45b with a higher apparent affinity and greater extent of folding. The
      Unc45-Hsp90 chaperone complex acts late in the folding pathway and promotes motor
      domain maturation after release from the ribosome. Unc45a behaves kinetically as
      an activator of the folding reaction by stimulating the rate of the Hsp90
      dependent folding by >20-fold with an apparent K(act) of 33 nm. This analysis of
      vertebrate Unc45 isoforms clearly demonstrates a direct role for Unc45 in Hsp90
      mediated myosin motor domain folding and highlights major differences between the
      isoforms in substrate specificity and mechanism.

PMID- 18326488
TI  - Novel oxidative stress-responsive gene ERS25 functions as a regulator of the heat
      shock and cell death response.
AB  - Members of the yeast p24 family, including Emp24p and Erv25p, exist as
      heteromeric complexes that have been proposed to cycle between the endoplasmic
      reticulum (ER) and Golgi compartments. The specific functions and sites of action
      of p24 proteins are still unknown. Here we identified a human homolog of the
      yeast p24 family of proteins, named ERS25 (endoplasmic reticulum stress-response
      protein 25), and investigated its role in stress response. ERS25 is predicted to
      have an ER localization signal peptide, a GOLD (Golgi dynamics) domain, which is
      found in several eukaryotic Golgi and lipid-trafficking proteins, a coiled-coil
      region, and a transmembrane domain. We demonstrate that ERS25 is localized to the
      ER and is induced by ER-specific stress, heat shock, and oxidative stress. The
      selective induction of ERS25 by brefeldin A, but not tunicamycin, implicates the
      involvement of ERS25 in protein trafficking between the ER and the Golgi. Small
      interfering RNA-mediated inhibition of ERS25 results in a significant decrease in
      apoptosis as well as a reduction of reactive oxygen species induced by oxidative
      stress. Moreover, ERS25 depletion results in a significant increase in the levels
      of the ER chaperone HSP70 in response to heat-shock stress through increased
      levels of HSF-1. We also found that inhibition of ERS25 induction in response to
      heat shock enhanced the binding of HSP70 to Apaf-1, which is likely to interfere
      in stress-mediated apoptosis. Together, the data presented here demonstrate that
      ERS25 may play a critical role in regulation of heat-shock response and
      apoptosis.

PMID- 18326489
TI  - Calmodulin binding and Cdk5 phosphorylation of p35 regulate its effect on
      microtubules.
AB  - In the nervous system, Cdk5 and its neuronal activator p35 are involved in the
      control of various activities, including neuronal differentiation and migration.
      Recently, we have reported that p35 is a microtubule-associated protein that
      regulates microtubule dynamics ( Hou, Z., Li, Q., He, L., Lim, H. Y., Fu, X.,
      Cheung, N. S., Qi, D. X., and Qi, R. Z. (2007) J. Biol. Chem. 282, 18666-18670 ).
      Here we present two regulatory modes of p35 function as a microtubule-associated
      protein. First, p35 is Ca(2+)-dependent calmodulin (CaM)-binding protein. The CaM
      and microtubule binding domains are localized to overlapping regions at the N
      terminus of p35. Within the CaM-binding region, Ala substitution for Trp-52
      abolishes the CaM-binding activity, corroborating specific CaM-binding of p35.
      Furthermore, CaM blocks p35 association with microtubules in a Ca(2+)-specific
      manner, suggesting that p35 may be involved in the Ca(2+)/CaM-mediated inhibition
      of microtubule assembly. Second, p35 phosphorylation by Cdk5 interferes with the
      microtubule-binding and polymerizing activities of p35. Using a mutational
      approach, we found that only phosphorylation at Thr-138, one of the two residues
      primarily phosphorylated in vivo, inhibits the polymerizing activity. In PC12
      cells, expression of p35 promotes nerve growth factor-induced neurite outgrowth
      under a Cdk5 inhibitory condition. Such p35 activity is impaired by the
      phosphomimetic mutation of Thr-138. These data suggest that Thr-138
      phosphorylation plays a critical role in the control of the p35 functions in
      microtubule assembly and neurite outgrowth.

PMID- 18326490
TI  - Small molecule activator of the human epithelial sodium channel.
AB  - The epithelial sodium channel (ENaC), a heterotrimeric complex composed of alpha,
      beta, and gamma subunits, belongs to the ENaC/degenerin family of ion channels
      and forms the principal route for apical Na(+) entry in many reabsorbing
      epithelia. Although high affinity ENaC blockers, including amiloride and
      derivatives, have been described, potent and specific small molecule ENaC
      activators have not been reported. Here we describe compound S3969 that fully and
      reversibly activates human ENaC (hENaC) in an amiloride-sensitive and dose
      dependent manner in heterologous cells. Mechanistically, S3969 increases hENaC
      open probability through interactions requiring the extracellular domain of the
      beta subunit. hENaC activation by S3969 did not require cleavage by the furin
      protease, indicating that nonproteolyzed channels can be opened. Function of
      alphabetaG37Sgamma hENaC, a channel defective in gating that leads to the salt
      wasting disease pseudohypoaldosteronism type I, was rescued by S3969. Small
      molecule activation of hENaC may find application in alleviating human disease,
      including pseudohypoaldosteronism type I, hypotension, and neonatal respiratory
      distress syndrome, when improved Na(+) flux across epithelial membranes is
      clinically desirable.

PMID- 18326491
TI  - Characterization of the Arabidopsis heterotrimeric G protein.
AB  - We have used fluorescence resonance energy transfer and co-immunoprecipitation to
      analyze the interactions among the alpha, beta, and gamma1 subunits of the
      Arabidopsis heterotrimeric G protein. Using cyan and yellow fluorescent protein
      fusion constructs, we show that overexpressed Ggamma1 localizes to protoplast
      membranes, but Gbeta exhibits membrane localization only when the Ggamma1 protein
      is co-overexpressed. Overexpressed Galpha shows membrane localization
      unaccompanied by overexpression of either Gbeta or Ggamma1. We detect
      fluorescence resonance energy transfer between Gbeta and Ggamma1 in the absence
      of Galpha overexpression and between Galpha and Ggamma1 but only when all three
      subunits are co-overexpressed. Both Galpha and Gbeta are associated with large
      macromolecular complexes of approximately 700 kDa in the plasma membrane. Galpha
      is present in both large complexes and as free Galpha in plasma membranes from
      wild type plants. In plants homozygous for a null allele of the Gbeta gene,
      Galpha is associated with smaller complexes in the 200-400-kDa range, indicating
      that its presence in the large complex depends on association with Gbetagamma.
      Activation of the Galpha subunit with guanosine 5'-3-O-(thio)triphosphate
      (GTPgammaS) results in partial dissociation of Galpha from the complex. Hydrogen
      peroxide (H2O2) promotes extensive dissociation of the Galpha complex but does
      not interfere with binding of GTPgammaS to purified recombinant Galpha,
      suggesting that reactive oxygen species affect the stability of the large complex
      but not the activity of Galpha itself.

PMID- 18326492
TI  - Primary platelet signaling cascades and integrin-mediated signaling control ADP
      ribosylation factor (Arf) 6-GTP levels during platelet activation and
      aggregation.
AB  - Previous studies showed that ADP-ribosylation factor 6 (Arf6) is important for
      platelet function; however, little is known about which signaling events regulate
      this small GTP-binding protein. Arf6-GTP was monitored in platelets stimulated
      with a number of agonists (TRAP, thrombin, convulxin, collagen, PMA,
      thapsigargin, or A23187) and all led to a time-dependent decrease in Arf6-GTP.
      ADP and U46619 were without effect. Using inhibitors, it was shown that the
      decrease of Arf6-GTP is a direct consequence of known signaling cascades. Upon
      stimulation via PAR receptors, Arf6-GTP loss could be blocked by treatment with U
      73122, BAPTA/AM, Ro-31-8220, or Go6976, indicating requirements for phospholipase
      C, calcium, and protein kinase C (PKC) alpha/beta, respectively. The Arf6-GTP
      decrease in convulxin-stimulated platelets showed similar requirements and was
      also sensitive to piceatannol, wortmannin, and LY294002, indicating additional
      requirements for Syk and phosphatidylinositol 3-kinase. The convulxin-induced
      decrease was sensitive to both PKCalpha/beta and delta inhibitors. Outside-in
      signaling, potentially via integrin engagement, caused a second wave of signaling
      that affected Arf6. Inclusion of RGDS peptides or EGTA, during activation, led to
      a biphasic response; Arf6-GTP levels partially recovered upon continued
      incubation. A similar response was seen in beta3 integrin-null platelets. These
      data show that Arf6-GTP decreases in response to known signaling pathways
      associated with PAR and GPVI. They further reveal a second, aggregation
      dependent, process that dampens Arf6-GTP recovery. This study demonstrates that
      the nucleotide state of Arf6 in platelets is regulated during the initial phases
      of activation and during the later stages of aggregation.

PMID- 18326493
TI  - Histone code modifications repress glucose transporter 4 expression in the
      intrauterine growth-restricted offspring.
AB  - We examined transcriptional and epigenetic mechanism(s) behind diminished
      skeletal muscle GLUT4 mRNA in intrauterine growth-restricted (IUGR) female rat
      offspring. An increase in MEF2D (inhibitor) with a decline in MEF2A (activator)
      and MyoD (co-activator) binding to the glut4 promoter in IUGR versus control was
      observed. The functional role of MEF2/MyoD-binding sites and neighboring three
      CpG clusters in glut4 gene transcription was confirmed in C2C12 muscle cells. No
      differential methylation of these three and other CpG clusters in the glut4
      promoter occurred. DNA methyltransferase 1 (DNMT1) in postnatal, DNMT3a, and
      DNMT3b in adult was differentially recruited with increased MeCP2 (methyl CpG
      binding protein) concentrations to bind the IUGR glut4 gene. Covalent
      modifications of the histone (H) code consisted of H3.K14 de-acetylation by
      recruitment of histone deacetylase (HDAC) 1 and enhanced association of HDAC4
      enzymes. This set the stage for Suv39H1 methylase-mediated di-methylation of
      H3.K9 and increased recruitment of heterochromatin protein 1alpha, which
      partially inactivates postnatal and adult IUGR glut4 gene transcription. Further
      increased interactions in the adult IUGR between DNMT3a/DNMT3b and HDAC1 and
      MEF2D and HDAC1/HDAC4 and decreased association between MyoD and MEF2A existed.
      We conclude that epigenetic mechanisms consisting of histone code modifications
      repress skeletal muscle glut4 transcription in the postnatal period and persist
      in the adult female IUGR offspring.

PMID- 18326494
TI  - Interleukin-5 receptor subunit oligomerization and rearrangement revealed by
      fluorescence resonance energy transfer imaging.
AB  - Interleukin (IL)-5 exerts hematopoietic functions through binding to the IL-5
      receptor subunits, alpha and betac. Specific assembly steps of full-length
      subunits as they occur in cell membranes, ultimately leading to receptor
      activation, are not well understood. We tracked the oligomerization of IL-5
      receptor subunits using fluorescence resonance energy transfer (FRET) imaging.
      Full-length IL-5Ralpha and betac were expressed in Phoenix cells as chimeric
      proteins fused to enhanced cyan or yellow fluorescent protein (CFP or YFP,
      respectively). A time- and dose-dependent increase in FRET signal between IL
      5Ralpha-CFP and betac-YFP was observed in response to IL-5, indicative of
      heteromeric receptor alpha-betac subunit interaction. This response was inhibited
      by AF17121, a peptide antagonist of IL-5Ralpha. Substantial FRET signals with
      betac-CFP and betac-YFP co-expressed in the absence of IL-5Ralpha demonstrated
      that betac subunits exist as preformed homo-oligomers. IL-5 had no effect on this
      betac-alone FRET signal. Interestingly, the addition of IL-5 to cells co
      expressing betac-CFP, betac-YFP, and nontagged IL-5Ralpha led to further increase
      in FRET efficiency. Observation of preformed betac oligomers fits with the view
      that this form can lead to rapid cellular responses upon IL-5 stimulation. The IL
      5-induced effects on betac assembly in the presence of nontagged IL-5Ralpha
      provide direct evidence that IL-5 can cause higher order rearrangements of betac
      homo-oligomers. These results suggest that IL-5 and perhaps other betac cytokines
      (IL-3 and granulocyte/macrophage colony-stimulating factor) trigger cellular
      responses by the sequential binding of cytokine ligand to the specificity
      receptor (subunit alpha), followed by binding of the ligand-subunit alpha complex
      to, and consequent rearrangement of, a ground state form of betac oligomers.

PMID- 18326495
TI  - A close-up view of the VraSR two-component system. A mediator of Staphylococcus
      aureus response to cell wall damage.
AB  - Staphylococcus aureus remains a clinical scourge. Recent studies have revealed
      that S. aureus is capable of mounting a response to antibiotics that target cell
      wall peptidoglycan biosynthesis, such as beta-lactams and vancomycin. A
      phosphotransfer-mediated signaling pathway composed of a histidine protein
      kinase, VraS, and a response regulator protein, VraR, has been linked to the
      coordination of this response. Herein, we report for the first time on the signal
      transduction mechanism of the VraSR system. We found that VraS is capable of
      undergoing autophosphorylation in vitro and its phosphoryl group is rapidly
      transferred to VraR. In addition, phosphorylated VraR undergoes rapid
      dephosphorylation by VraS. Evidence is presented that VraR has adopted a novel
      strategy in regulating the output response of the VraSR-mediated signaling
      pathway. The VraR effector domain inhibits formation of inactive VraR dimers and,
      in doing so, it holds the regulatory domain into an intermediate active state. We
      show that only phosphorylation induces formation of the biological active VraR
      dimer species. Furthermore, we propose that damage inflicted to cell wall
      peptidoglycan could be the main source of the stimuli that VraR responds to due
      to the tight control that VraS has on the phosphorylation state of VraR. Our
      findings provide for the first time insights into the molecular basis for the
      proposed role of VraSR as a "sentinel" system capable of rapidly sensing cell
      wall peptidoglycan damage and coordinating a response that enhances the
      resistance phenotype in S. aureus.

PMID- 18326496
TI  - Cardiolipin controls the osmotic stress response and the subcellular location of
      transporter ProP in Escherichia coli.
AB  - The phospholipid composition of the membrane and transporter structure control
      the subcellular location and function of osmosensory transporter ProP in
      Escherichia coli. Growth in media of increasing osmolality increases, and entry
      to stationary phase decreases, the proportion of phosphatidate in anionic lipids
      (phosphatidylglycerol (PG) plus cardiolipin (CL)). Both treatments increase the
      CL:PG ratio. Transporters ProP and LacY are concentrated with CL (and not PG)
      near cell poles and septa. The polar concentration of ProP is CL-dependent. Here
      we show that the polar concentration of LacY is CL-independent. The osmotic
      activation threshold of ProP was directly proportional to the CL content of wild
      type bacteria, the PG content of CL-deficient bacteria, and the anionic lipid
      content of cells and proteoliposomes. CL was effective at a lower concentration
      in cells than in proteoliposomes, and at a much lower concentration than PG in
      either system. Thus, in wild type bacteria, osmotic induction of CL synthesis and
      concentration of ProP with CL at the cell poles adjust the osmotic activation
      threshold of ProP to match ambient conditions. ProP proteins linked by
      homodimeric, C-terminal coiled-coils are known to activate at lower osmolalities
      than those without such structures and coiled-coil disrupting mutations raise the
      osmotic activation threshold. Here we show that these mutations also prevent
      polar concentration of ProP. Stabilization of the C-terminal coiled-coil by
      covalent cross-linking of introduced Cys reverses the impact of increasing CL on
      the osmotic activation of ProP. Association of ProP C termini with the CL-rich
      membrane at cell poles may raise the osmotic activation threshold by blocking
      coiled-coil formation. Mutations that block coiled-coil formation may also block
      association of the C termini with the CL-rich membrane.

PMID- 18326497
TI  - Mechanism of ceftriaxone induction of excitatory amino acid transporter-2
      expression and glutamate uptake in primary human astrocytes.
AB  - Glutamate is an essential neurotransmitter regulating brain functions. Excitatory
      amino acid transporter (EAAT)-2 is one of the major glutamate transporters
      primarily expressed in astroglial cells. Dysfunction of EAAT2 is implicated in
      acute and chronic neurological disorders, including stroke/ischemia, temporal
      lobe epilepsy, amyotrophic lateral sclerosis, Alzheimer disease, human
      immunodeficiency virus 1-associated dementia, and growth of malignant gliomas.
      Ceftriaxone, one of the beta-lactam antibiotics, is a stimulator of EAAT2
      expression with neuroprotective effects in both in vitro and in vivo models based
      in part on its ability to inhibit neuronal cell death by glutamate
      excitotoxicity. Based on this consideration and its lack of toxicity, ceftriaxone
      has potential to manipulate glutamate transmission and ameliorate neurotoxicity.
      We investigated the mechanism by which ceftriaxone enhances EAAT2 expression in
      primary human fetal astrocytes (PHFA). Ceftriaxone elevated EAAT2 transcription
      in PHFA through the nuclear factor-kappaB (NF-kappaB) signaling pathway. The
      antibiotic promoted nuclear translocation of p65 and activation of NF-kappaB. The
      specific NF-kappaB binding site at the -272 position of the EAAT2 promoter was
      responsible for ceftriaxone-mediated EAAT2 induction. In addition, ceftriaxone
      increased glutamate uptake, a primary function of EAAT2, and EAAT2 small
      interference RNA completely inhibited ceftriaxone-induced glutamate uptake
      activity in PHFA. Taken together, our data indicate that ceftriaxone is a potent
      modulator of glutamate transport in PHFA through NF-kappaB-mediated EAAT2
      promoter activation. These findings suggest a mechanism for ceftriaxone
      modulation of glutamate transport and for its potential effects on ameliorating
      specific neurodegenerative diseases through modulation of extracellular
      glutamate.

PMID- 18326498
TI  - Pellino 3b negatively regulates interleukin-1-induced TAK1-dependent NF kappaB
      activation.
AB  - IL-1 receptor-associated kinase (IRAK) is phosphorylated, ubiquitinated, and
      degraded upon interleukin-1 (IL-1) stimulation. In this study, we showed that
      IRAK can be ubiquitinated through both Lys-48- and Lys-63-linked polyubiquitin
      chains upon IL-1 induction. Pellino 3b is the RING-like motif ubiquitin protein
      ligase that promotes the Lys-63-linked polyubiquitination on IRAK. Pellino 3b
      mediated Lys-63-linked IRAK polyubiquitination competed with Lys-48-linked IRAK
      polyubiquitination for the same ubiquitination site, Lys-134 of IRAK, thereby
      blocking IL-1-induced IRAK degradation. Importantly, the negative impact of
      Pellino 3b on IL-1-induced IRAK degradation correlated with the inhibitory effect
      of Pellino 3b on the IL-1-induced TAK1-dependent pathway, suggesting that a
      positive role of IRAK degradation in IL-1 induced TAK1 activation. Taken
      together, our results suggest that Pellino 3b acts as a negative regulator for IL
      1 signaling by regulating IRAK degradation through its ubiquitin protein ligase
      activity.

PMID- 18326499
TI  - Determination and functional analysis of the consensus binding site for TFII-I
      family member BEN, implicated in Williams-Beuren syndrome.
AB  - The ubiquitously expressed TFII-I family of multifunctional transcription factors
      is involved in gene regulation as well as signaling. Despite the fact that they
      share significant sequence homology, these factors exhibit varied and distinct
      functions. The lack of knowledge about its binding sites and physiological target
      genes makes it more difficult to assign a definitive function for the TFII-I
      related protein, BEN. We set out to determine its optimal binding site with the
      notion of predicting its physiological target genes. Here we report the
      identification of an optimal binding sequence for BEN by SELEX (systematic
      evolution of ligands by exponential enrichment) and confirm the relevance of this
      sequence by functional assays. We further performed a data base search to assign
      genes that have this consensus site(s) and validate several candidate genes by
      quantitative PCR upon stable silencing of BEN and by chromatin
      immunoprecipitation assay upon stable expression of BEN. Given that
      haploinsufficiency in BEN is causative to Williams-Beuren syndrome, these results
      may further lead to the identification of a set of physiologically relevant
      target genes for BEN and may help identify molecular determinants of Williams
      Beuren syndrome.

PMID- 18326500
TI  - Functional requirement for Orai1 in store-operated TRPC1-STIM1 channels.
AB  - Orai1 and TRPC1 have been proposed as core components of store-operated calcium
      release-activated calcium (CRAC) and store-operated calcium (SOC) channels,
      respectively. STIM1, a Ca(2+) sensor protein in the endoplasmic reticulum,
      interacts with and mediates store-dependent regulation of both channels. We have
      previously reported that dynamic association of Orai1, TRPC1, and STIM1 is
      involved in activation of store-operated Ca(2+) entry (SOCE) in salivary gland
      cells. In this study, we have assessed the molecular basis of TRPC1-SOC channels
      in HEK293 cells. We report that TRPC1+STIM1-dependent SOCE requires functional
      Orai1. Thapsigargin stimulation of cells expressing Orai1+STIM1 increased Ca(2+)
      entry and activated typical I(CRAC) current. STIM1 alone did not affect SOCE,
      whereas expression of Orai1 induced a decrease. Expression of TRPC1 induced a
      small increase in SOCE, which was greatly enhanced by co-expression of STIM1.
      Thapsigargin stimulation of cells expressing TRPC1+STIM1 activated a non
      selective cation current, I(SOC), that was blocked by 1 microm Gd(3+) and 2-APB.
      Knockdown of Orai1 decreased endogenous SOCE as well as SOCE with TRPC1 alone.
      siOrai1 also significantly reduced SOCE and I(SOC) in cells expressing
      TRPC1+STIM1. Expression of R91WOrai1 or E106QOrai1 induced similar attenuation of
      TRPC1+STIM1-dependent SOCE and I(SOC), whereas expression of Orai1 with
      TRPC1+STIM1 resulted in SOCE that was larger than that with Orai1+STIM1 or
      TRPC1+STIM1 but not additive. Additionally, Orai1, E106QOrai1, and R91WOrai1 co
      immunoprecipitated with similar levels of TRPC1 and STIM1 from HEK293 cells, and
      endogenous TRPC1, STIM1, and Orai1 were co-immunoprecipitated from salivary
      glands. Together, these data demonstrate a functional requirement for Orai1 in
      TRPC1+STIM1-dependent SOCE.

PMID- 18326502
TI  - Incentives to quit smoking in primary care.

PMID- 18326503
TI  - Effect on smoking quit rate of telling patients their lung age: the Step2quit
      randomised controlled trial.
AB  - OBJECTIVE: To evaluate the impact of telling patients their estimated spirometric
      lung age as an incentive to quit smoking. DESIGN: Randomised controlled trial.
      SETTING: Five general practices in Hertfordshire, England. PARTICIPANTS: 561
      current smokers aged over 35. INTERVENTION: All participants were offered
      spirometric assessment of lung function. Participants in intervention group
      received their results in terms of "lung age" (the age of the average healthy
      individual who would perform similar to them on spirometry). Those in the control
      group received a raw figure for forced expiratory volume at one second (FEV1).
      Both groups were advised to quit and offered referral to local NHS smoking
      cessation services. MAIN OUTCOME MEASURES: The primary outcome measure was
      verified cessation of smoking by salivary cotinine testing 12 months after
      recruitment. Secondary outcomes were reported changes in daily consumption of
      cigarettes and identification of new diagnoses of chronic obstructive lung
      disease. RESULTS: Follow-up was 89%. Independently verified quit rates at 12
      months in the intervention and control groups, respectively, were 13.6% and 6.4%
      (difference 7.2%, P=0.005, 95% confidence interval 2.2% to 12.1%; number needed
      to treat 14). People with worse spirometric lung age were no more likely to have
      quit than those with normal lung age in either group. Cost per successful quitter
      was estimated at 280 pounds sterling (366 euros, $556). A new diagnosis of
      obstructive lung disease was made in 17% in the intervention group and 14% in the
      control group; a total of 16% (89/561) of participants. CONCLUSION: Telling
      smokers their lung age significantly improves the likelihood of them quitting
      smoking, but the mechanism by which this intervention achieves its effect is
      unclear. TRIAL REGISTRATION: National Research Register N0096173751.

PMID- 18326504
TI  - Characterization of the GNAQ promoter and association of increased Gq expression
      with cardiac hypertrophy in humans.
AB  - AIMS: Transgenic mice with cardiac overexpression of Gq develop cardiac
      hypertrophy, apoptosis, and heart failure. Similar mechanisms may contribute to
      human left ventricular hypertrophy (LVH). However, mechanisms regulating
      transcription of the human GNAQ gene encoding the Gq protein are unknown and
      single-nucleotide polymorphisms have not been reported. METHODS AND RESULTS: We
      delineated essential elements for transcription in the human GNAQ promoter using
      reporter assays and showed promoter induction by serum and angiotensin II.
      Sequencing of the whole promoter revealed a common (minor allele frequency 0.48)
      dinucleotide polymorphism at position -694/-695, resulting in an exchange of two
      adjacent nucleotides (TT > GC). The GC allele had increased transcription factor
      binding and was associated with enhanced transcriptional activation by serum or
      angiotensin II, resulting in enhanced Gq expression and intracellular signalling.
      Genotyping a population-based survey (n = 1204) revealed a higher prevalence of
      LVH in individuals with the GC/GC genotype [odds ratio (OR) 4.07; 95% CI 1.63
      10.16; P = 0.003], this effect being more pronounced in women (OR 5.52; P =
      0.005). CONCLUSION: A novel polymorphism in the Gq promoter region is associated
      with enhanced promoter activity, Gq expression, intracellular signal
      transduction, and increased prevalence of LVH, particularly in women.

PMID- 18326505
TI  - Radiopaque thrombus in right ventricle.

PMID- 18326506
TI  - Primary chylopericardium due to lymphangiectasias: the crucial role of
      lymphangiography.

PMID- 18326507
TI  - MiSearch adaptive pubMed search tool.
AB  - MiSearch is an adaptive biomedical literature search tool that ranks citations
      based on a statistical model for the likelihood that a user will choose to view
      them. Citation selections are automatically acquired during browsing and used to
      dynamically update a likelihood model that includes authorship, journal and
      PubMed indexing information. The user can optionally elect to include or exclude
      specific features and vary the importance of timeliness in the ranking.
      AVAILABILITY: http://misearch.ncibi.org. SUPPLEMENTARY INFORMATION: Supplementary
      data are available at Bioinformatics online.

PMID- 18326508
TI  - 3D-Garden: a system for modelling protein-protein complexes based on
      conformational refinement of ensembles generated with the marching cubes
      algorithm.
AB  - MOTIVATION: Reliable structural modelling of protein-protein complexes has
      widespread application, from drug design to advancing our knowledge of protein
      interactions and function. This work addresses three important issues in protein
      protein docking: implementing backbone flexibility, incorporating prior
      indications from experiment and bioinformatics, and providing public access via a
      server. 3D-Garden (Global And Restrained Docking Exploration Nexus), our
      benchmarked and server-ready flexible docking system, allows sophisticated
      programming of surface patches by the user via a facet representation of the
      interactors' molecular surfaces (generated with the marching cubes algorithm).
      Flexibility is implemented as a weighted exhaustive conformer search for each
      clashing pair of molecular branches in a set of 5000 models filtered from around
      approximately 340,000 initially. RESULTS: In a non-global assessment, carried out
      strictly according to the protocols for number of models considered and model
      quality of the Critical Assessment of Protein Interactions (CAPRI) experiment,
      over the widely-used Benchmark 2.0 of 84 complexes, 3D-Garden identifies a set of
      ten models containing an acceptable or better model in 29/45 test cases,
      including one with large conformational change. In 19/45 cases an acceptable or
      better model is ranked first or second out of 340,000 candidates. AVAILABILITY:
      http://www.sbg.bio.ic.ac.uk/3dgarden (server).

PMID- 18326509
TI  - Bovine sertoli cells colonize and form tubules in murine hosts following
      transplantation and grafting procedures.
AB  - The contribution of somatic cells to nonrodent male germ cell transplantation
      success has not been well established due to lack of cell type-specific markers
      to distinguish donor cells from host cells. In the present study, we first
      screened antibodies and a lectin to identify markers suitable for unequivocal
      distinction between germ cells and Sertoli cells in bovine testes compared with
      mouse testes. Anti-vimentin and the Dolichos biflorus agglutinin (DBA) lectin
      detected only bovine Sertoli cells and spermatogonia, respectively; anti-NONO and
      anti-GCNA1 detected only mouse Sertoli and germ cells, respectively. The outcome
      of transplanting bovine testis cells into nude mouse testes was then studied
      using these markers. Our results clearly showed that immature bovine Sertoli
      cells survive and colonize mouse testes at 2.5 months after transplantation and
      that tubular structures composed of donor Sertoli cells formed adjacent to murine
      tubules within the host mouse testis. Bovine germ cell colonization and survival
      in mouse testes after transplantation were confirmed, but this was restricted to
      areas of bovine Sertoli cell colonization. In addition, ectopic grafts of intact
      bovine testis tissue and cell aggregates from hanging drop cultures were placed
      under the back skin and testis capsule of nude mice. Bovine Sertoli cells in
      ectopic grafts and aggregates were able to form tubular structures, and some
      bovine germ cells were observed around 2 months after implantation. This study
      therefore identifies a practical strategy to assess the outcome of testicular
      cell transplantation using different antibodies and a lectin to distinguish
      bovine cells from mouse cells. It identifies an approach that can readily be
      adapted to study other nonrodent species.

PMID- 18326510
TI  - Permanent third-degree atrioventricular block as clinical presentation of an
      intracardiac bronchogenic cyst.
AB  - Bronchogenic cysts are the most common primary cysts in the mediastinum. However,
      intracardiac bronchogenic cysts are uncommon. The present case represents a
      unique situation, in which an intracardiac bronchogenic cyst at the region of the
      atrioventricular node presented as permanent complete atrioventricular block
      (AVB) and was associated with the presence of an ostium secundum atrial septal
      defect.

PMID- 18326511
TI  - Commentary: Evaluating response to heat waves.

PMID- 18326512
TI  - Cohort Profile: the Swiss National Cohort--a longitudinal study of 6.8 million
      people.

PMID- 18326514
TI  - A two-step serum-free culture system supports development of human oocytes from
      primordial follicles in the presence of activin.
AB  - BACKGROUND: The objective of this study was to determine whether follicles grown
      within human ovarian cortical strip culture for 6 days in serum-free medium could
      be isolated at the secondary stage of pre-antral development and grown in vitro
      to the late pre-antral/early antral stage during a 4 day culture period. METHODS:
      Ovarian cortical biopsies were obtained from six women aged 26-40 years, with
      informed consent, during elective Caesarean section. Small tissue slices of
      ovarian cortex, with underlying stromal tissue removed, were cultured in serum
      free medium for 6 days and at the end of this period pre-antral (secondary)
      follicles were dissected from the strips. Seventy-four intact pre-antral
      follicles ranging in size (66-132 microm) (mean size 100 microm +/- 3.4) were
      selected for further culture. Follicles were placed individually within V-shaped
      microwell culture plates in serum-free medium in the presence (n = 38) or absence
      (n = 36) of 100 ng/ml of human recombinant activin A. RESULTS: Pre-antral
      follicles grown for 4 days in the presence of activin A grew to a larger size
      (mean diameter 143 microm +/- 7.4) than those grown in control medium (mean
      diameter 111 microm +/- 8) (P < 0.005). Ninety percent of follicles cultured in
      the presence of activin A increased in size during the first 2 days of culture
      compared with only 36% of follicles in control medium (P > 0.005). Of the
      follicles surviving the entire culture period, 30% of those cultured in the
      presence of activin A showed normal morphology with intact oocytes and antral
      formation. None of the follicles grown in control medium developed antral
      cavities and >90% of those follicles collected at the end of the culture period
      showed signs of oocyte degeneration. CONCLUSIONS: The results reported here
      demonstrate that under certain conditions, it is possible to achieve accelerated
      oocyte/follicle development from human primordial/primary follicles. This
      provides the first encouraging step towards achieving full in vitro growth of
      human oocytes.

PMID- 18326513
TI  - Cohort Profile: The Diabetes Study of Northern California (DISTANCE)--objectives
      and design of a survey follow-up study of social health disparities in a managed
      care population.

PMID- 18326515
TI  - Nuclear staining identifies two populations of human sperm with different DNA
      fragmentation extent and relationship with semen parameters.
AB  - BACKGROUND: Sperm DNA fragmentation is a possible predictive parameter for male
      fertility status. The occurrence of M540 bodies in semen of subfertile subjects
      affects flow cytometric investigations in sperm. We set up a new method to
      evaluate DNA fragmentation excluding M540 bodies. METHODS: DNA fragmentation was
      evaluated by flow cytometry in semen of 75 subjects both by terminal
      deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end labeling (TUNEL,
      traditional method) and by double staining with TUNEL and propidium iodide (PI,
      new method). RESULTS: The use of the new method revealed that TUNEL
      underestimates sperm DNA fragmentation in flow cytometry and showed two sperm
      populations stained with low (PI(dim)) and high (PI(br)) avidity for PI. The
      PI(dim) population is entirely composed of DNA fragmented sperm and its incidence
      shows highly significant negative correlations with morphology, motility, sperm
      count and concentration (respectively, r = -0.51, -0.52, -0.46 and -0.32, n =
      75). DNA fragmentation in the PI(br) sperm population is independent from semen
      quality. CONCLUSIONS: The correlations between sperm DNA breakage and semen
      quality previously reported are mainly driven by the occurrence of the PI(dim)
      population. DNA fragmented sperm in this population are more likely to have
      poorer morphology, reduced motility and thus a reduced chance to fertilize an
      oocyte than DNA damaged sperm in PI(br) population. Distinguishing between the
      two types of sperm DNA fragmentation appears to be important in clinical
      investigations.

PMID- 18326516
TI  - Do we need to search for gr/gr deletions in infertile men in a clinical setting?
AB  - BACKGROUND: Partial deletions of the AZFc region of the Y chromosome such as
      gr/gr deletions have been detected in infertile patients as well as in control
      groups. The impact of these gr/gr deletions on the etiology of male infertility
      remains unknown. In the present study, we investigated the presence of gr/gr
      deletions in Caucasian men. METHODS: gr/gr deletions were analyzed by using
      markers sY1291, sY1191 and sY1197 and by investigating the presence of single
      nucleotide variants (SNV) in DAZ and CDY1 genes in patients with azoospermia (n =
      44), cryptozoospermia (n = 51) or severe oligozoospermia (n = 92). Control groups
      consisted of men with normal spermatogenesis on testicular biopsy (n = 33),
      normozoospermia (n = 278) or proven fertility (n = 83). RESULTS: We observed 20
      gr/gr deletions, with eight in infertile patients (4.3%) and 12 in the control
      groups (3.0%), which was not significantly different. DAZ SNV analysis revealed
      eight different deletion patterns in patients and controls. CONCLUSIONS: In the
      present study, no significant differences in the frequency of gr/gr deletions
      between different patient and control groups were observed. We concluded that the
      relationship between gr/gr deletions and male infertility remains unclear and
      that it is too early to systematically test for gr/gr deletions for infertile
      couples seeking assisted reproduction treatment.

PMID- 18326517
TI  - Change, change, change: hormonal actions depend on changes in blood levels.
AB  - The main hypothesis outlined in this communication is that changes in hormonal
      levels are of utmost importance in the female reproductive system physiology.
      Hormone measurements must be assessed in the context of time and change. We
      hypothesize that changes in hormone concentrations carry significant biological
      messages, much more than a given level at a given time point and if proved, this
      theory could give rise to better approaches to treatment, and risk assessment.

PMID- 18326518
TI  - Captan exposure and evaluation of a pesticide exposure algorithm among orchard
      pesticide applicators in the Agricultural Health Study.
AB  - Pesticide exposure assessment in the Agricultural Health Study (AHS) has relied
      upon two exposure metrics: lifetime exposure days and intensity-weighted lifetime
      exposure days, the latter incorporating an intensity score computed from a
      questionnaire-based algorithm. We evaluated this algorithm using actual fungicide
      exposure measurements from AHS private orchard applicators. Captan was selected
      as a marker of fungicide exposure. Seventy-four applicators from North Carolina
      and Iowa growing apples and/or peaches were sampled on 2 days they applied captan
      in 2002 and 2003. Personal air, hand rinse, 10 dermal patches, a pre-application
      first-morning urine and a subsequent 24-h urine sample were collected from each
      applicator per day. Environmental samples were analyzed for captan, and urine
      samples were analyzed for cis-1,2,3,6-tetrahydrophthalimide (THPI). Task and
      personal protective equipment information needed to compute an individual's
      algorithm score was also collected. Differences in analyte detection frequency
      were tested in a repeated logistic regression model. Mixed-effects models using
      maximum-likelihood estimation were employed to estimate geometric mean exposures
      and to evaluate the measured exposure data against the algorithm. In general,
      captan and THPI were detected significantly more frequently in environmental and
      urine samples collected from applicators who used air blast sprayers as compared
      to those who hand sprayed. The AHS pesticide exposure intensity algorithm, while
      significantly or marginally predictive of thigh and forearm captan exposure,
      respectively, did not predict air, hand rinse or urinary THPI exposures. The
      algorithm's lack of fit with some exposure measures among orchard fungicide
      applicators may be due in part to the assignment of equal exposure weights to air
      blast and hand spray application methods in the current algorithm. Some
      modification of the algorithm is suggested by these results.

PMID- 18326519
TI  - Remission of diabetes while on sunitinib treatment for renal cell carcinoma.

PMID- 18326520
TI  - Bortezomib, doxorubicin and dexamethasone in advanced multiple myeloma.
AB  - BACKGROUND: Bortezomib has shown significant activity in myeloma. In this
      multicenter trial, we assessed for the first time the combination of bortezomib,
      doxorubicin and low-dose dexamethasone (PAd) in the treatment of
      relapsed/refractory myeloma. PATIENTS AND METHODS: Sixty-four patients were
      treated for a median of four 28-day cycles (1-6). Bortezomib was given at 1.3
      mg/m(2) (days 1, 4, 8, 11) and dexamethasone at 40 mg (days 1-4); 34 patients
      receive doxorubicin at 20 mg/m(2) (days 1, 4) while 30 patients pegylated
      liposomal doxorubicin at 30 mg/m(2) (day 1). RESULTS: Fifty-eight percent of
      patients had undergone prior autologous transplantation, 70% prior anthracycline
      and 27% prior bortezomib-based regimens. Forty-three patients (67%) achieved at
      least a partial response including 16 (25%) with at least a very good partial
      response. One-year event-free survival was 34% after PAd and 31% after the
      previous line of therapy (hazard ratio 1.20, 95% confidence interval 0.76-1.90, P
      = 0.43). One-year overall survival from the start of PAd was 66%. Grade 3-4 toxic
      effects included thrombocytopenia (48%), neutropenia (36%), infections (15%),
      anemia (13%), gastrointestinal disturbances (11%) and peripheral neuropathy
      (10%). Two patients had grade 3-4 cardiac heart failure. CONCLUSIONS: PAd is an
      active salvage therapy with manageable toxicity in patients with
      relapsed/refractory myeloma.

PMID- 18326521
TI  - The influence of moderate hypercapnia on neural activity in the anesthetized
      nonhuman primate.
AB  - Hypercapnia is often used as vasodilatory challenge in clinical applications and
      basic research. In functional magnetic resonance imaging (fMRI), elevated CO(2)
      is applied to derive stimulus-induced changes in the cerebral rate of oxygen
      consumption (CMRO(2)) by measuring cerebral blood flow and blood-oxygenation
      level-dependent (BOLD) signal. Such methods, however, assume that hypercapnia has
      no direct effect on CMRO(2). In this study, we used combined intracortical
      recordings and fMRI in the visual cortex of anesthetized macaque monkeys to show
      that spontaneous neuronal activity is in fact significantly reduced by moderate
      hypercapnia. As expected, measurement of cerebral blood volume using an exogenous
      contrast agent and of BOLD signal showed that both are increased during
      hypercapnia. In contrast to this, spontaneous fluctuations of local field
      potentials in the beta and gamma frequency range as well as multiunit activity
      are reduced by approximately 15% during inhalation of 6% CO(2) (pCO(2) = 56
      mmHg). A strong tendency toward a reduction of neuronal activity was also found
      at CO(2) inhalation of 3% (pCO(2) = 45 mmHg). This suggests that CMRO(2) might be
      reduced during hypercapnia and caution must be exercised when hypercapnia is
      applied to calibrate the BOLD signal.

PMID- 18326522
TI  - Segregation of visual selection and saccades in human frontal eye fields.
AB  - The premotor theory of attention suggests that target processing and generation
      of a saccade to the target are interdependent. Temporally precise transcranial
      magnetic stimulation (TMS) was delivered over the human frontal eye fields, the
      area most frequently associated with the premotor theory in association with eye
      movements, while subjects performed a visually instructed pro-/antisaccade task.
      Visual analysis and saccade preparation were clearly separated in time, as
      indicated by 2 distinct time points of TMS delivery that resulted in elevated
      saccade latencies. These results show that visual analysis and saccade
      preparation, although frequently enacted together, are dissociable processes.

PMID- 18326523
TI  - Increased adhesive properties of neutrophils in sickle cell disease may be
      reversed by pharmacological nitric oxide donation.
AB  - Increased leukocyte adhesion to vascular endothelium contributes to vaso
      occlusion in sickle cell disease. Since nitric oxide bioavailability is decreased
      in sickle cell disease and nitric oxide may inhibit leukocyte adhesion, we
      investigated whether stimulation of NO-signaling pathways can reduce the adhesive
      properties of neutrophils from sickle cell disease individuals (sickle cell
      diseaseneu). sickle cell diseaseneu presented greater adhesion in vitro to both
      fibronectin and ICAM-1 than control neutrophils. Co-incubation of sickle cell
      diseaseneu with the nitric oxide-donor agents, sodium nitroprusside and
      dietheylamine NONOate (DEANO), and the guanylate cyclase stimulator, BAY41-2272,
      all significantly reduced the increased adhesion to fibronectin/ICAM-1.
      Oxadiazolo[4,3-a]quinoxalin-1-one, a guanylate cyclase inhibitor, reversed sodium
      nitroprusside/DEANO-diminished adhesion to fibronectin, implicating cGMP
      dependent signaling in this mechanism. Interestingly, intracellular cGMP was
      significantly higher in neutrophils from sickle cell disease individuals on
      hydroxyurea (sickle cell diseaseHUneu). Accordingly, sickle cell diseaseHUneu
      adhesion to fibronectin/ICAM-1 was significantly lower than that of sickle cell
      diseaseneu. Agents that stimulate the nitric oxide/cGMP-dependent pathway may
      have beneficial effects on leukocyte function if used in these subjects.

PMID- 18326524
TI  - Primary extramedullary plasmacytoma: similarities with and differences from
      multiple myeloma revealed by interphase cytogenetics.
AB  - Primary extramedullary plasmacytoma is an indolent neoplasm that infrequently
      converts to multiple myeloma. Since cytogenetic data on extramedullary
      plasmacytoma are lacking, we studied 38 cases of this type of neoplasm by
      fluorescence in situ hybridization. Fourteen cases (37%) contained IGH breaks,
      including six with a t(4;14) translocation. No translocations t(11;14), t(14;16),
      t(8;14), nor breaks involving MALT1, BCL6 or FOXP1 were found. Loss of 13q (40%),
      as well as chromosomal gains (82%) were common. There was no correlation between
      chromosomal alterations and clinical features or local relapse. Cytogenetically,
      extramedullary plasmacytoma and multiple myeloma are closely related. However,
      the distribution of IGH translocation partners, with the notable absence of
      t(11;14), is different. Key words: extramedullary plasmacytoma, multiple myeloma,
      cytogenetics, IGH translocation, fluorescence in situ hybridization.

PMID- 18326525
TI  - Peptide-nucleic acid-mediated enriched polymerase chain reaction as a key point
      for non-invasive prenatal diagnosis of beta-thalassemia.
AB  - The presence of fetal DNA in maternal plasma can be exploited to develop new
      procedures for non-invasive prenatal diagnosis. Tests to detect 7 frequent beta
      globin gene mutations in people of Mediterranean origin were applied to the
      analysis of maternal plasma in couples where parents carried different mutations.
      A mutant enrichment amplification protocol was optimized by using peptide nucleic
      acids (PNAs) to clamp maternal wild-type alleles. By this approach, 41 prenatal
      diagnoses were performed by microelectronic microchip analysis, with total
      concordance of results obtained on fetal DNA extracted from chorionic villi.
      Among these, 27/28 were also confirmed by direct sequencing and 4 by
      pyrosequencing.

PMID- 18326526
TI  - Hepatocyte growth factor promotes migration of human myeloma cells.
AB  - Multiple myeloma is characterized by the accumulation and dissemination of
      malignant plasma cells in the bone marrow. Cell migration is thought to be
      important for these events. We studied migration in a Transwell two-chamber assay
      and tested the motogenic effect of various cytokines. In addition to insulin-like
      growth factor-1 and stromal cell-derived growth factor-1alpha, previously known
      as chemoattractants for myeloma cells, we identified hepatocyte growth factor as
      a potent attractant for myeloma cells. Hepatocyte growth factor-mediated
      migration was dependent on phosphatidylinositol-3-kinase, involved the MAPK/Erk
      signaling cascade and VLA-4 integrins, but did not involve Akt, mTOR or G
      proteins.

PMID- 18326527
TI  - Differential role of CD97 in interleukin-8-induced and granulocyte-colony
      stimulating factor-induced hematopoietic stem and progenitor cell mobilization.
AB  - CD97 is broadly expressed on hematopoietic cells and is involved in neutrophil
      migration. Since neutrophils are key regulators in HSC/HPC mobilization, we
      studied a possible role for CD97 in interleukin-8 and granulocyte-colony
      stimulating factor-induced HSC/HPC mobilization. Mobilization was absent in mice
      receiving CD97 mAb followed by interleukin-8, while granulocyte-colony
      stimulating factor-induced mobilization remained unaltered following anti-CD97
      administration. Furthermore, combined administration of CD97 mAb and IL-8 induced
      a significant reduction in the neutrophilic compartment. We hypothesize that the
      absence of interleukin-8-induced HSC/HPC mobilization after CD97 mAb
      administration is due to its effect on neutrophil function.

PMID- 18326528
TI  - Accurate Rh phenotype determination by reticulocyte mRNA typing shortly after
      multiple transfusions.
AB  - Alloimmunization is a common phenomenon after transfusion, with an estimated
      incidence of 0.5% increasing to 20-60% in chronically transfused patients. In
      recently transfused patients, serological typing can be hampered by mixed field
      agglutination. We established RT-PCR methods for RHD, RHC/c and RHE/e typing
      using mRNA from reticulocytes. Molecular typing was performed soon after 51
      separate mismatched transfusion events involving 30 patients. Accurate
      identification of the transfused patients' phenotype was confirmed in all cases.
      Reticulocyte maturation studies revealed that temperature is a crucial parameter
      for transition into mature red blood cells.

PMID- 18326529
TI  - Errorless learning for training individuals with schizophrenia at a community
      mental health setting providing work experience.
AB  - The effects of errorless learning (EL) on work performance, tenure, and personal
      well-being were compared with conventional job training in a community mental
      health fellowship club offering 12-week time-limited work experience.
      Participants were 40 clinically stable schizophrenia and schizoaffective disorder
      outpatients randomly assigned to EL vs conventional instruction (CI) at a thrift
      type clothing store. EL participants received training on how to perform their
      assigned job tasks based on principles of EL, such as error reduction and
      automation of task performance. CI participants received training common to other
      community-based entry-level jobs that included verbal instruction, a visual
      demonstration, independent practice, and corrective feedback. Participants were
      scheduled to work 2 hours per week for 12 weeks. For both groups, job training
      occurred during the first 2 weeks at the worksite. Work performance (assessed
      using the Work Behavior Inventory, WBI) and personal well-being (self-esteem, job
      satisfaction, and work stress) were assessed at weeks 2, 4, and 12. Job tenure
      was defined as the number of weeks on the job or total number of hours worked
      prior to quitting or study end. The EL group performed better than the CI group
      on the Work Quality Scale from the WBI, and the group differences were relatively
      consistent over time. Results from the survival analyses of job tenure revealed a
      non-significant trend favoring EL. There were no group differences on self
      esteem, job satisfaction, or work stress. The findings provide modest support for
      the extensions of EL to community settings for enhancing work performance.

PMID- 18326530
TI  - An improved assay for radiation-induced chromatid breaks using a colcemid block
      and calyculin-induced PCC combination.
AB  - We report on a new method for the study of radiation-induced chromatid breaks in
      stimulated human peripheral blood T lymphocytes, involving a combination of a 1-h
      colcemid block and a short (15 min) calyculin A treatment. We find that this
      procedure eliminates the problem of centromere splitting when calyculin A is used
      alone for a longer period and produces metaphase spreads with superior quality.
      By this procedure, the chromosomes and the chromatid breaks are expanded and
      thereby make for improved break scoring. In a comparison of the new technique
      with the conventional colcemid block method, we show a close proportionality
      between the frequencies of chromatid breaks scored with the two methods. The
      frequency of chromatid breaks with the new method was found to be significantly
      higher than that with colcemid alone, adding a higher sensitivity to the assay as
      an additional advantage.

PMID- 18326531
TI  - Recommendations for design of the rat comet assay.
AB  - Although the rodent comet assay is gaining acceptance as a standard technique for
      evaluating DNA damage in vivo, there is no internationally accepted guideline for
      its conduct and several aspects of its experimental design have not been
      optimized. For example, no standard positive control is used, there is no
      agreement on how tissue toxicity should be measured and sources of experimental
      variability have not been considered in relation to experimental design. This
      study showed that methylnitrosourea is a good alternative positive control
      inducing DNA damage in all tissues examined (stomach, liver, blood and bone
      marrow) over a dose range of 25-100 mg/kg at both 3 and 24 h after treatment. At
      the highest dose, significant toxicity was seen in all tissues using the neutral
      diffusion assay and also by histopathological/haematological analysis, except in
      the liver where no change was seen even 7 days after dosing. Analyses using
      control data pooled from several studies showed that, as expected, the greatest
      variability was seen between tissue preparations from different animals and that
      different numbers of animals were required to detect the same fold increases in
      different tissues. Power analyses showed that, preparing three gels for each
      tissue and scoring 50 nuclei per gel, a group of six animals allows 2-fold
      increases over control in the liver, bone marrow and stomach and a 3-fold
      increase in blood to be detected with 80% probability. It is recommended that
      similar investigations of experimental variability should be performed to
      determine optimal experimental design in any laboratory using the rodent comet
      assay.

PMID- 18326532
TI  - Imatinib for the treatment of refractory, diffuse systemic sclerosis.

PMID- 18326533
TI  - Comment on: Modelling the cost effectiveness of TNF antagonists in the management
      of rheumatoid arthritis: results from the British Society for Rheumatology
      Biologics Registry.

PMID- 18326534
TI  - Synovial detection and autoantibody reactivity of processed citrullinated
      isoforms of vimentin in inflammatory arthritides.
AB  - OBJECTIVES: To investigate the presence and characteristics of citrullinated
      vimentin in protein extracts of inflamed synovial tissue. METHODS: Cytosolic
      protein extracts obtained from RA (n = 14) and SpA patients (n = 14) were
      analysed by gel electrophoresis and western blotting. Citrullinated vimentin
      isoforms were visualized by a combination of anti-modified citrulline (AMC)
      staining and anti-vimentin detections (V9, H-84). This was subsequently confirmed
      by immunoprecipitation. Autoantibody detection was verified using sera obtained
      form RA (n = 6) and SpA (n = 6) patients. RESULTS: A specific cluster of spots
      displayed on the 2D gel images of cytosolic synovial tissue extracts, was
      identified by mass spectrometry as vimentin. Interestingly, our results suggested
      that these isoforms could be the result of caspase cleavage. In addition, these
      cleaved forms of vimentin were found to be citrullinated in synovial cytosolic
      protein extracts of inflammatory arthritides, mainly in RA patients. Caspase-3 is
      able to cleave vimentin at amino acid 85. Western blot analysis with a specific
      antibody against amino acids 1-84 of vimentin (H-84) confirmed that the
      citrullinated isoforms of vimentin were lacking this part of the protein. These
      results were also confirmed by immunoprecipitation of vimentin derived from
      cytosolic protein extracts of RA and SpA patients. Furthermore, the presence of
      autoantibodies against these citrullinated processed forms of vimentin was found
      to be predominantly associated with RA patients. CONCLUSIONS: These findings show
      the presence of processed citrullinated vimentin in inflammatory arthritides,
      mainly in RA and suggest a possible origin of the ACPA immune response in RA.

PMID- 18326535
TI  - Occurrence of cold agglutinin disease in RA patient during etanercept therapy
      successfully treated with rituximab.

PMID- 18326537
TI  - Prevention of corticosteroid-induced osteonecrosis in rabbits by intra-bone
      marrow injection of autologous bone marrow cells.
AB  - OBJECTIVES: Femoral head osteonecrosis (ON) is a serious complication of steroid
      administration. We evaluated bone marrow transplantation (BMT) for preventing
      corticosteroid-induced ON. METHODS: Rabbits, injected with methylprednisolone
      (MPSL; 20 mg/kg), were divided into four groups: (i) MPSL alone; MPSL injection
      only, (ii) MPSL+needling; 2 days after MPSL injection, a hole (1.2 mm diameter)
      was drilled from the outer cortex 2.5 cm distal to the proximal end of the
      greater trochanter, (iii) MPSL+saline; 2 days after MPSL injection, 2 ml saline
      was injected directly into the bone marrow cavity, and (iv) MPSL+BMT; 2 days
      after MPSL injection, 1 x 10(7)/2 ml bone marrow cells (BMCs) were injected
      directly into the bone marrow cavity. Platelets, fibrinogen, prothrombin time and
      total cholesterol in peripheral blood were measured before and after treatment.
      Tissues were stained with haematoxylin and eosion and terminal deoxynucleotidyl
      mediated deoxyuridine triphosphate nick-end labelling stain and immunostained for
      VEGF, while cell proliferation and viability of whole BMCs in the femur were
      analysed by cell cycle analysis and [(3)H]-thymidine uptake. RESULTS: The ON
      incidence in rabbits treated with MPSL alone, MPSL+needling and MPSL+saline was
      72.7, 70.0 and 66.7%, respectively, while in the MPSL+BMT group, the incidence
      was 0%. Serological findings in the MPSL+BMT group were almost normalized. VEGF
      and TUNEL staining were reduced in the MPSL+BMT group compared with all other
      groups. There were significantly fewer BMCs in G1 phase from the MPSL+BMT group
      than the other groups, while uptake of [(3)H]-thymidine was significantly
      increased. CONCLUSION: Direct injection of autologous BMCs into femurs prevents
      corticosteroid-induced ON following treatment with high-dose, short-term
      steroids.

PMID- 18326538
TI  - Comment on: Delay in presentation to primary care physicians is the main reason
      why patients with rheumatoid arthritis are seen late by rheumatologists.

PMID- 18326539
TI  - Dysphagia and other manifestations of oesophageal involvement in the
      musculoskeletal diseases.
AB  - Oesophageal dysfunction can occur in a variety of musculoskeletal conditions,
      most notably the autoimmune connective tissue diseases. However, correlation
      between oesophageal symptoms and investigations is frequently poor. It is often
      uncertain whether symptoms are caused by the underlying disease or by its
      treatment. As the primary disease process may not be responsive to treatment,
      correctable iatrogenic causes should always be sought.

PMID- 18326541
TI  - Opioid rotation from oral morphine to oral oxycodone in cancer patients with
      intolerable adverse effects: an open-label trial.
AB  - OBJECTIVE: We prospectively investigated the efficacy of opioid rotation from
      oral morphine to oral oxycodone in cancer patients who had difficulty in
      continuing oral morphine treatment because of inadequate analgesia and/or
      intolerable side effects. METHODS: Twenty-seven patients were enrolled and 25
      were evaluated. The rate of patients who achieved adequate pain control, which
      provided an indication of treatment success, was evaluated as primary endpoint.
      The acceptability and pharmacokinetics of oxycodone were evaluated in addition to
      the assessment of analgesic efficacy and safety during the study period. RESULTS:
      In spite of intense pain, the morphine daily dose could not be increased in most
      patients before the study because of intolerable side effects. However, switching
      to oral oxycodone allowed approximately 1.7-fold increase as morphine equivalent
      dose. Consequently, 84.0% (21/25) of patients achieved adequate pain control. By
      the end of the study, all patients except one had tolerated the morphine-induced
      intolerable side effects (i.e. nausea, vomiting, constipation, drowsiness).
      Common side effects (>10%) that occurred during the study were typically known
      for strong opioid analgesics, and most were mild to moderate in severity. A
      significant negative correlation between creatinine clearance (CCr) value and the
      trough concentrations of the morphine metabolites was observed. On the other
      hand, no significant correlation was found between CCr value and the
      pharmacokinetic parameters of oxycodone or its metabolites. CONCLUSIONS: For
      patients who had difficulty in continuing oral morphine treatment, regardless of
      renal function, opioid rotation to oral oxycodone may be an effective approach to
      alleviate intolerable side effects and pain.

PMID- 18326542
TI  - Constitutive components and induced gene expression are involved in the
      desiccation tolerance of Selaginella tamariscina.
AB  - Selaginella tamariscina, one of the most primitive vascular plants, can remain
      alive in a desiccated state and resurrect when water becomes available. To
      evaluate the nature of desiccation tolerance in this plant, we compared the
      composition of soluble sugars and saturation ratios of phospholipids (PLs)
      between hydrated and desiccated tissues of S. tamariscina using gas
      chromatography. In this study, differences in gene expression and ABA contents
      were also analyzed during dehydration. The results revealed that trehalose (at
      >130 mg g(-1) DW) was the major soluble sugar, and low saturated fatty acid
      content in PLs (0.31) was maintained in both hydrated and desiccated tissues. In
      addition, the ABA content of S. tamariscina increased 3-fold, and genes involved
      in ABA signaling and cellular protection were up-regulated while photosystem
      related genes were down-regulated during dehydration. The biochemical and
      molecular findings suggest that both constitutive and inducible protective
      molecules contribute to desiccation tolerance of S. tamariscina.

PMID- 18326543
TI  - Systems biotechnology of mammalian cell factories.
AB  - The increasing demand for recombinant therapeutic proteins has placed significant
      pressure on the biopharmaceutical industry to develop high-yielding, mammalian
      cell-based production systems. Current efforts to increase the production of
      recombinant proteins by mammalian host cells largely proceed by the lengthy
      screening of clonal derivatives rather than by directed genetic or metabolic
      engineering. However, the advent of systems biology has created a new set of
      tools that will ensure that future engineering strategies will be informed by an
      understanding of the genetic/regulatory and metabolic networks that determine the
      functional competence of mammalian cell factories in vitro. In this review we
      summarize recent systems-level studies that utilize genome-scale analytical tools
      to analyse the functional basis for key production process characteristics such
      as high cell-specific productivity, correct product processing and rapid cell
      proliferation in the in vitro environment. We also describe the use of high
      throughput -omic technologies to investigate how mammalian cell factories respond
      to environmental and metabolic perturbation.

PMID- 18326544
TI  - Automated extraction of meaningful pathways from quantitative proteomics data.
AB  - Technological developments in the life sciences have resulted in an ever
      accelerating pace of data production. Systems Biology tries to shed light upon
      these data by building complex models describing the interactions between
      biological components. However, extracting information from this morass of data
      requires the use of sophisticated computational techniques. Here, we propose a
      method suitable to integrate data drawn from quantitative proteomics into a
      metabolic scaffold and identify the metabolic pathways which are collectively up
      regulated or down-regulated. The availability of such a tool is highly desirable
      as the extracted information could then be taken as a starting point for in-depth
      analyses, in particular in fields like Synthetic Biology, where datasets need be
      characterized routinely.

PMID- 18326545
TI  - Functional genomics in translational cancer research: focus on breast cancer.
AB  - Conventional molecular and genetic methods for studying cancer are limited to the
      analysis of one locus at a time. A cluster of genes that are regulated together
      can be identified by DNA microarray, and the functional relationships can uncover
      new aspects of cancer biology. Breast cancer can be used to provide a model to
      demonstrate the current approaches to the molecular analysis of cancer. Meta
      analysis is an important tool for the identification and validation of
      differentially expressed genes to increase power in clinical and biological
      studies across different sets of data. Recently, meta-analysis approaches have
      been applied to large collections of microarray datasets to investigate molecular
      commonalities of multiple cancer types not only to find the common molecular
      pathways in tumour development but also to compare the individual datasets to
      other cancer datasets to identify new sets of genes. Several investigators agree
      that microarray results should be validated. One commonly used method is
      quantitative reverse transcription PCR (qRT-PCR) to validate the expression
      profiles of the target genes obtained through microarray experiments. qRT-PCR is
      attractive for clinical use, since it can be automated and performed on fresh or
      archived formalin-fixed, paraffin-embedded tissue samples. The outcome of these
      analyses might accelerate the application of basic research findings into daily
      clinical practice through translational research and may have an impact on
      foreseeing the clinical outcome, predicting tumour response to specific therapy,
      identification of new prognostic biomarkers, discovering targets for the
      development of novel therapies and providing further insights into tumour
      biology.

PMID- 18326546
TI  - Platelet-derived growth factors (PDGF-A and -B) and their receptors in human
      fetal and adult ovaries.
AB  - There is no information regarding the presence of platelet-derived growth factors
      (PDGFs) and their receptors in human ovaries. The expression of PDGF-A, -B and
      their two receptors, PDGFR-alpha and -beta, was investigated in ovarian samples
      from women/girls and from human fetuses, at the protein and mRNA levels. The
      samples were prepared for immunohistochemical staining for PDGF-A and -B and
      their two receptors and in situ hybridization for the detection of the mRNA
      transcripts of the receptors. Total RNA was extracted from frozen ovarian
      samples, and the expression of PDGF-A and -B was investigated by reverse
      transcription-polymerase chain reaction. The proteins for PDGF-A and -B were
      detected in oocytes, and in granulosa cells (GC) of 50% of the follicles from
      women/girls. The proteins and mRNA transcripts for the two receptors were
      detected in oocytes (mRNA for PDGFR-beta only in 25% of the oocytes). PDGFR-alpha
      mRNA was expressed in GC of a minority of the samples from women/girls, whereas
      PDGFR-beta protein and mRNA were identified in over 50% of the GC from this
      source. PDGF-A and -B transcripts were identified in all the extracts. The
      presence of the receptors in GC suggests that PDGFs might be involved in the
      activation of primordial follicles.

PMID- 18326547
TI  - Identification of new breakpoints in AZFb and AZFc.
AB  - Microdeletions in AZFa, AZFb and AZFc regions lead to different patterns of male
      infertility, from severe oligozoospermia to non-obstructive azoospermia.
      Intrachromosomal homologous recombination mechanisms were already identified in
      patients with simultaneous microdeletions in the AZFb and AZFc regions. Ten
      patients with atypical AZFb and AZFc deletion patterns were studied. The
      definition of those microdeletions and the fine characterization of the
      respective breakpoints were performed using sequence tagged sites/single
      nucleotide variants-PCR and DNA sequencing. Y-chromosome haplogroups were
      determined to establish a putative association with the patterns obtained. Seven
      deletion patterns were identified, P5/terminal (30%; 3/10), P5/P1 distal (20%;
      2/10), IR4/distal-P2, IR2/proximal-P1, IR4/distal-P1, P4/terminal and complete
      AZFb/c deletion (10%; 1/10). Breakpoint sequence analysis suggests that only in
      one patient the P5/P1 distal deletion pattern was due to a homologous
      recombination mechanism. Sequence alignment of the other deletion patterns
      suggest that they have resulted from non-homologous recombination mechanisms.

PMID- 18326548
TI  - Comorbidity of alcohol and substance dependence with attention
      deficit/hyperactivity disorder (ADHD).
AB  - AIMS: Attention-deficit/hyperactivity disorder (ADHD) is of great clinical
      importance not only because of its high prevalence but also due to the frequent
      comorbid illnesses that are connected with this disorder. Several studies were
      able to demonstrate that ADHD constitutes a significant risk factor for the
      exacerbation of habit-forming illnesses, i.e. addictions. METHODS: We conducted a
      study on 152 adult patients with alcohol dependence (n = 91) or multiple
      substance addiction (n = 61) to determine whether or not these patients were
      affected by ADHD. For retrospective assessment of childhood ADHD, the WURS-k was
      used as well as the DSM-IV symptom checklist for ADHD. The CAARS was used to
      assess the persisting symptoms of ADHD in adults. RESULTS: 20.9% (WURS-k) or
      23.1% (DSM-IV diagnostic criteria) of the alcohol-dependent patients showed
      evidence of retrospective ADHD affliction in childhood. With the help of CAARS,
      ADHD was proved to be persistent in 33.3% of the adult patients. In the group of
      substance-addicted patients 50.8% (WURS-k) and 54.1% (DSM-IV) presented with
      diagnostic criteria for ADHD in childhood and 65.5% (CAARS) showed evidence of
      ADHD persisting in adulthood. CONCLUSIONS: These results reveal that habit
      forming illnesses can be associated with a high comorbidity with ADHD, expressed
      in the form of alcohol abuse and also in consumption of illegal drugs. The
      results underline the great importance of early and adequate diagnostics and
      therapy of ADHD for the prevention of habit-forming illnesses.

PMID- 18326549
TI  - Improvement of knowledge, attitude, and behavior about oral health in a
      population of alcohol addicted persons.
AB  - AIMS: To improve knowledge, attitude, and behavior about oral health and oral
      cancer prevention in a population of alcohol-addicted persons involved in a
      residential rehabilitation program in Italy. METHODS: A questionnaire was
      administered to obtain socioeconomic and oral risk factors data, and a complete
      dental examination was performed. A lecture on oral health risk factors and
      healthy behaviors was delivered. A pre-post test questionnaire was used to assess
      the short-term effectiveness of the intervention. Long-term effectiveness was
      assessed by a follow-up interview at 1 year from the intervention. The
      independent effect of several covariates on oral health at baseline and on the
      outcome of the intervention was evaluated. RESULTS: Seventy-six individuals from
      the residential alcohol rehabilitation program participated in our study. About
      half had been addicted to alcohol for more than 10 years; 81.6% smoked at the
      time of survey; 31.0% declared that they never used toothbrushes or that they
      brushed less than once/day. We found an improvement of 25.0% in exact answers
      between the pre-post test questionnaire. At 1 year from the intervention, the 42
      participants who reached follow up showed a great improvement in knowledge and
      attitude towards oral health. In particular, toothbrushing had become a daily
      routine after every meal for 67.1% of participants. CONCLUSIONS: Education of
      alcohol-dependent individuals in a rehabilitation setting may contribute to their
      attention to oral health and willingness to change habits.

PMID- 18326550
TI  - Alterations of serum brain-derived neurotrophic factor levels in early alcohol
      withdrawal.
AB  - AIMS: Alcohol withdrawal-enhanced neurotoxicity contributes to the addictive
      process. Brain-derived neurotrophic factor (BDNF) plays an important role in
      neuronal plasticity and learning. In this study, we explored the changes of serum
      BDNF levels in alcoholic patients at baseline and after one-week alcohol
      withdrawal. METHODS: Twenty-five alcoholic patients were admitted for alcohol
      detoxification treatment, and 22 healthy control subjects were also enrolled. We
      collected blood samples of the patient group on the first and seventh day of
      alcohol withdrawal, and measured serum BDNF level with sandwich enzyme-linked
      immunosorbent assay. The severity of withdrawal symptoms was evaluated by the
      Clinical Institute Withdrawal Assessment-Alcohol, Revised every eight hours.
      RESULTS: Serum BDNF levels did not differ significantly between alcoholic
      patients and control subjects. But BDNF levels were found to be significantly
      increased one week after alcohol withdrawal (from 13.9 +/- 3.8 ng/ml to 15.4 +/-
      3.8 ng/ml, P = 0.03). A significant positive correlation was found between
      baseline BDNF level and baseline withdrawal severity (r = 0.45, P = 0.03).
      CONCLUSIONS: The present study suggests that elevated serum BDNF levels were
      found in early alcohol withdrawal, implying that BDNF may involve in
      neuroadaptation during the period.

PMID- 18326551
TI  - Characterization of a functional (pro)renin receptor in rat brain neurons.
AB  - (Pro)renin receptor (PRR), the newest member of the renin-angiotensin system
      (RAS), is turning out to be an important player in the regulation of the
      cardiovascular system. It plays a pivotal role in activation of the local RAS and
      stimulates signalling pathways involved in proliferative and hypertrophic
      mechanisms. However, the role of PRR in the brain remains unknown. Thus, our
      objective in this study was to determine whether a functional PRR is present in
      neurons within the brain. Neuronal co-cultures from the hypothalamus and
      brainstem areas of neonatal rat brain express PRR mRNA. Immunoreactivity for PRR
      was primarily localized on the neuronal cell soma and in discrete areas in the
      neurites. Treatment of neurons with renin, in the presence of 2 microm losartan,
      caused a time- and dose-dependent stimulation of phosphorylation of extracellular
      signal related kinase ERK1 (p44) and ERK2 (p42) isoforms of mitogen-activated
      protein kinase. Optimal stimulation of fourfold was observed within 2 min with 20
      nm renin. Electrophysiological recordings showed that treatment of the neurons
      with renin, in the presence of 2 microm losartan, resulted in a steady and stable
      decrease in action potential frequency. A 46% decrease in action potential
      frequency was observed within 5 min of treatment and was attenuated by co
      incubation with a PRR blocking peptide. These observations demonstrate that the
      PRR is present in neurons within the brain and that its activation by renin
      initiates the MAP kinase signalling pathway and inhibition of neuronal activity.

PMID- 18326552
TI  - Altered central catecholaminergic transmission and cardiovascular disease.
AB  - Numerous studies, some of which date back more than three decades, have
      established a link between disorders of the cardiovascular system and the
      catecholaminergic system of the brain. Central noradrenergic (and putative
      adrenergic) neurones are involved in numerous brain functions, and there appears
      to be more than one mechanism via which a dysfunction of central nor/adrenergic
      signalling may be detrimental to the cardiovascular system. Moreover, in some
      cases, such as essential hypertension, altered noradrenergic transmission could
      play a causative role. Numerous controversies are evident throughout the
      literature, which are very difficult to explain without much better understanding
      of the basic physiology of central noradrenergic transmission. Recently, using a
      combination of novel molecular, electrochemical and imaging techniques, we have
      started to unravel how noradrenergic neurones in the brain store and release
      their transmitter. Targeted long-term modulation of specific noradrenergic cell
      groups in defined brain areas using viral gene transfer is helping to clarify the
      links between central catecholamines and cardiovascular control in health and
      disease. These studies may reveal new therapeutic strategies for various
      cardiovascular diseases which are accompanied by heightened sympathetic nerve
      activity.

PMID- 18326553
TI  - A sympathetic view of the sympathetic nervous system and human blood pressure
      regulation.
AB  - New ideas about the relative importance of the autonomic nervous system (and
      especially its sympathetic arm) in long-term blood pressure regulation are
      emerging. It is well known that mean arterial blood pressure is normally
      regulated in a fairly narrow range at rest and that blood pressure is also able
      to rise and fall 'appropriately' to meet the demands of various forms of mental,
      emotional and physical stress. By contrast, blood pressure varies widely when the
      autonomic nervous system is absent or when key mechanisms that govern it are
      destroyed. However, 24 h mean arterial pressure is still surprisingly normal
      under these conditions. Thus, the dominant idea has been that the kidney is the
      main long-term regulator of blood pressure and the autonomic nervous system is
      important in short-term regulation. However, this 'renocentric' scheme can be
      challenged by observations in humans showing that there is a high degree of
      individual variability in elements of the autonomic nervous system. Along these
      lines, the level of sympathetic outflow, the adrenergic responsiveness of blood
      vessels and individual haemodynamic patterns appear to exist in a complex, but
      appropriate, balance in normotension. Furthermore, evidence from animals and
      humans has now clearly shown that the sympathetic nervous system can play an
      important role in longer term blood pressure regulation in both normotension and
      hypertension. Finally, humans with high baseline sympathetic traffic might be at
      increased risk for hypertension if the 'balance' among factors deteriorates or is
      lost. In this context, the goal of this review is to encourage a comprehensive
      rethinking of the complexities related to long-term blood pressure regulation in
      humans and promote finer appreciation of physiological relationships among the
      autonomic nervous system, vascular function, ageing, metabolism and blood
      pressure.

PMID- 18326554
TI  - Vasoconstrictor effect of aldosterone via angiotensin II type 1 (AT1) receptor:
      possible role of AT1 receptor dimerization.
AB  - AIMS: We recently demonstrated that aldosterone induces a non-genomic
      vasoconstrictor effect on rat coronary arterioles and that this effect was
      blocked by angiotensin II type 1 receptor (AT1) blockers. Intracellular
      transglutaminase enhances AT1 signalling by cross-linking AT1 homodimers. The
      purpose of this study was to confirm the AT1-dependency of the vasoconstrictor
      effect of aldosterone using AT1a knockout (AT1aKO) mice and to investigate the
      role of intracellular transglutaminase and AT1 dimerization in this effect.
      METHODS AND RESULTS: The mesenteric arterioles (60-160 microm) were isolated from
      C57BL/6J (wild-type, WT) and AT1aKO mice, and the internal diameter was measured
      by video microscopy. Aldosterone (10(-13) to 10(-6) M), but not hydrocortisone,
      produced a dose-dependent vasoconstriction in WT mice; the maximal diameter
      change was -8.6 +/- 0.3% from the baseline (P < 0.001). This vasoconstrictor
      effect was unaffected by the mineralocorticoid receptor antagonist spironolactone
      or eplerenone, the AT2 antagonist PD123319, the glucocorticoid receptor
      antagonist RU486, or endothelium denudation. Aldosterone's vasoconstrictor effect
      was negligible in AT1aKO mice. The AT1 blockers valsartan or candesartan
      suppressed aldosterone-induced vasoconstriction in WT mice. The transglutaminase
      inhibitors cystamine and monodansyl cadaverine also suppressed the
      vasoconstrictor effect of aldosterone, without affecting the vasoconstrictor
      effect of angiotensin II in WT mice. AT1 dimer protein levels were increased in
      WT mesenteric arterioles treated with 10(-7) M aldosterone, and the
      transglutaminase inhibitor and AT1 blocker blocked this aldosterone-induced
      formation of AT1 dimer. Treatment with 10(-7) M aldosterone for 10 min increased
      the transglutaminase activity by 2.5 +/- 0.2-fold in cultured vascular smooth
      muscle cells and by 1.2 +/- 0.1-fold in the mesenteric arterioles. These
      increases were abolished by transglutaminase inhibitors. CONCLUSION: Aldosterone
      produces a non-genomic, endothelium-independent vasoconstrictor effect by
      enhancing intracellular transglutaminase activity and presumably inducing AT1
      dimer formation in mesenteric arterioles.

PMID- 18326555
TI  - Imatinib mesylate attenuates fibrosis in coxsackievirus b3-induced chronic
      myocarditis.
AB  - AIMS: Coxsackievirus B3 (CVB3)-induced chronic myocarditis in mice is accompanied
      by severe fibrosis and by sustained elevation of platelet-derived growth factor
      (PDGF)-A, -B, and -C levels in the cardiac tissue. To test if PDGF stimulation of
      resident fibroblasts causally contributes to fibrosis, we employed inhibition of
      PDGF receptor signalling with the orally available kinase inhibitor Imatinib.
      METHODS AND RESULTS: Chronic myocarditis was induced by CVB3 infection of major
      histocompatibility complex (MHC) class II knockout (B6Aa(0)/Aa(0)) mice. The mice
      were treated with 100 mg/kg Imatinib or vehicle, respectively, twice daily for 34
      days. Expression of PDGF-C and of inflammatory cytokines were analysed by semi
      quantitative RT-PCR. PDGFalpha receptor phosphorylation was detected by
      immunoblotting of cardiac tissue extracts and in situ by immunohistochemistry.
      Fibrosis formation was analysed by Sirius-Red staining and hydroxyproline (HP)
      determination. Fibronectin, and tenascin expression was analysed by RT-PCR and
      immunohistochemistry. Matrix metalloproteinase (MMP) activity was assessed with
      collagen, synthetic peptides, and gelatine as substrates. Imatinib significantly
      inhibited the myocarditis-related PDGFalpha receptor activation in the heart
      tissue. The virus titres in the hearts, inflammatory infiltrations, and elevated
      PDGF levels were unaffected by the Imatinib treatment. A significant attenuation
      of fibrosis occurred in Imatinib-treated animals. The Sirius Red-stained fibrotic
      area was reduced from 5.30 +/- 0.50 to 3.21 +/- 0.35%, and the HP content was
      reduced from 362 +/- 43 to 238 +/- 32 microMol/10 mg dry weight vs. 190 +/- 27 in
      uninfected controls. The expression of fibronectin, EIIIA+ fibronectin, and
      tenascin C were likewise reduced. The diminished matrix protein deposition was
      not caused by elevated MMP activity, since MMP activity was not changed or even
      reduced under Imatinib. CONCLUSION: The data suggest a causal role for elevated
      PDGF expression and PDGF receptor activity in the pathogenesis of cardiac
      fibrosis.

PMID- 18326556
TI  - Recycling endosomes supply cardiac pacemaker channels for regulated surface
      expression.
AB  - AIMS: Cellular excitability is not only determined by the type but also by the
      number of ion channels in the plasma membrane. Recent evidence indicates that
      cell surface expression of cardiac pacemaker channels might be controlled beyond
      the level of biosynthesis by regulating their surface transport. However, neither
      the underlying trafficking pathways nor their molecular control have yet been
      investigated. METHODS AND RESULTS: We have studied endocytic trafficking of
      hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels expressed
      as fusions with green fluorescent protein or tagged with an extracellular
      haemagglutinin epitope in opossum kidney cells, dissociated rat hippocampal
      neurons, and ventricular cardiomyocytes. After being internalized from the plasma
      membrane, HCN2 and HCN4 are sorted to the Rab11-positive endocytic recycling
      compartment (ERC). From there, they are transported back to the cell surface
      depending on active phospholipase D2 (PLD2). The peptide hormone angiotensin II,
      which is upregulated in a number of cardiac pathologies and a known activator of
      PLD2, stimulates ERC trafficking of HCN4 channels. It significantly increases HCN
      surface expression independent of their biosynthesis. CONCLUSION: Recycling
      endosomes serve as an intracellular storage compartment for the cardiac pacemaker
      channels HCN2 and HCN4. They are not only crucial for maintaining a homeostatic
      surface expression but also supply channels for rapid adaptation of their surface
      expression in response to extracellular stimuli.

PMID- 18326557
TI  - Genomics in cardiac metabolism.
AB  - Cell biology is in transition from reductionism to a more integrated science.
      Large-scale analysis of genome structure, gene expression, and metabolites are
      new technologies available for studying cardiac metabolism in diseases known to
      modify cardiac function. These technologies have several limitations and this
      review aims both to assess and take a critical look at some important results
      obtained in genomics restricted to molecular genetics, transcriptomics and
      metabolomics of cardiac metabolism in pathophysiological processes known to alter
      myocardial function. Therefore, our goal was to delineate new signalling pathways
      and new areas of research from the vast amount of data already published on
      genomics as applied to cardiac metabolism in diseases such as coronary heart
      disease, heart failure, and ischaemic reperfusion.

PMID- 18326558
TI  - Heat shock proteins as molecular targets for intervention in atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained clinical tachyarrhythmia.
      AF is a progressive condition as demonstrated by the finding that maintenance of
      normal rhythm and contractile function becomes more difficult the longer AF
      exists. AF causes cellular stress, which induces atrial remodelling, involving
      reduction in the expression of L-type Ca(2+) channels and structural changes
      (myolysis), finally resulting in contractile dysfunction. Heat shock proteins
      (HSPs) comprise a family of proteins involved in the protection against different
      forms of cellular stress. Their classical function is the prevention of toxic
      protein aggregation by binding to (partially) unfolded proteins. Recent
      investigations reveal that HSPs prevent atrial remodelling and attenuate the
      promotion of AF in both cellular and animal experimental models. Furthermore,
      studies in humans suggest a protective role for HSPs against progression from
      paroxysmal AF to chronic, persistent AF. Therefore, manipulation of the HSP
      system may offer novel therapeutic approaches for the prevention of atrial
      remodelling. Such approaches may contribute to the maintenance or restoration of
      tissue integrity and contractile function. Ultimately, this concept may offer an
      additional treatment strategy to delay progression towards chronic AF and/or
      improve the outcome of cardioversion.

PMID- 18326559
TI  - Divinyl ether synthesis in garlic bulbs.
AB  - Formation of 13-lipoxygenase-derived divinyl ethers has been described in garlic
      bulbs. Here, the identification of a cDNA from garlic is described, which encodes
      for an enzyme that corresponds to divinyl ether synthases (DES). The recombinant
      protein was expressed in Escherichia coli and shown to metabolize 13-hydroperoxy
      as well as 9-hydroperoxy linole(n)ic acid to etherole(n)ic and colnele(n)ic acid,
      respectively. This biochemical feature classifies it as a member of the CYP74C
      subfamily of cytochrome P-450 enzymes. Product analysis after incubation of
      purified recombinant enzyme and fatty acid hydroperoxides revealed the formation
      of a mixture of different cis/trans isomers with one isomer often dominant. RNA
      blot analyses showed a constitutive expression of DES transcripts predominant in
      below-ground organs of garlic. By exogenous application of salicylic acid and
      sorbitol, but not by methyljasmonate, the transcript was also induced in leaves.
      Whereas the prominent divinyl ether in garlic was the 13-lipoxygenase-derived
      etheroleic acid, analysis of transgenic Arabidopsis expressing garlic DES showed
      that 9-lipoxygenase-derived colnelenic acid dominated 24 h after wounding. These
      data indicate that the product pattern of this DES from garlic depends on the
      substrate availability and that the enzyme is the first member in the group of
      9/13-DES.

PMID- 18326560
TI  - Integrin-linked kinase regulates cell proliferation and tumour growth in murine
      colitis-associated carcinogenesis.
AB  - BACKGROUND: Integrins are transmembrane cell surface receptors that mediate cell
      cell and cell-matrix contacts. Integrin-linked kinase (ILK) is the binding
      partner of beta1 and beta3 integrins, and has been ascribed essential roles in
      development, angiogenesis and tumourigenesis. However, in vivo evidence for the
      latter is currently lacking. AIM: The hypothesis that epithelial cell-specific
      deletion of ILK would impact on murine tumourigenesis was tested using a colitis
      associated cancer model. METHODS: To create intestinal epithelial cell ILK
      knockout animals, Fabp/Cre mice (Cre recombinase expressed under the control of a
      modified Fabp promoter) were used, and they were mated with mice carrying a loxP
      flanked (floxed) ILK gene (ILK(flox/flox)). RESULTS: ILK intestinal knockout mice
      exhibited a reduction in the size of the caecum, and reduced crypt height in the
      colon. Immunohistochemical analysis confirmed that there was diminished ILK
      expression, and bromodeoxyuridine (BrdU) staining was significantly reduced in
      the knockout animals as compared with the wild-type animals in both the caecum
      and colon (p<0.001 for both). Following azoxymethane and dextran sodium sulfate
      (DSS) treatment, fewer total tumours were observed in the ILK knockout animals,
      which were mosaic with respect to ILK expression. Cyclin D1, Snail, fibronectin
      and matrix metalloproteinase 9 (MMP9) were all reduced, and active caspase 3
      increased, in tumours from ILK knockout mice, as compared with wild-type mice, on
      immunohistochemical analysis. Using small interfering RNA (siRNA) to knock down
      ILK in colonic cancer cell lines, it was confirmed that it is capable of
      regulating cyclin D1, Snail, MMP9 and fibronectin transcription. CONCLUSIONS:
      From these findings, it is concluded that ILK plays an important role in
      intestinal epithelial cell proliferation, and that it influences the development
      of colitis-associated cancer, through modulation of cyclin D1, the extracellular
      matrix and MMP9.

PMID- 18326561
TI  - Vascular ultrasound for the pre-operative evaluation prior to arteriovenous
      fistula formation for haemodialysis: review of the evidence.

PMID- 18326562
TI  - Association of inflammation with anaemia in patients with chronic kidney disease
      not requiring chronic dialysis.
AB  - BACKGROUND: Anaemia associated with chronic kidney disease (CKD) has substantial
      public health importance. However, the association of haemoglobin concentrations
      with inflammation in the setting of decreased kidney function is not well
      established. METHODS: We analysed cross-sectional data from 7389 outpatient
      adults, who were referred by general practitioners for routine blood testing
      between June 2006 and June 2007. Glomerular filtration rate (eGFR) was estimated
      by the abbreviated Modification of Diet in Renal Disease (MDRD) equation.
      Multivariable linear regression analysis was used to identify factors
      independently associated with haemoglobin concentrations across eGFR categories
      as the main outcome. RESULTS: Of the 7389 participants included in the analytic
      cohort 2221 (30.1%) participants had eGFR >/=90 mL/min/m(2), 4310 (58.3%) 60-89
      mL/min/m(2) and 858 (11.6%) <60 mL/min/m(2). There were significant, graded,
      increases in high sensitivity C-reactive protein (hs-CRP) and haemoglobin
      concentrations across eGFR categories independent of age, gender, plasma glucose
      and lipids (P < 0.0001 for trends). In the multivariable regression analysis,
      increased hs-CRP concentrations were independently associated with lower
      haemoglobin concentrations at different stages of eGFR (P < 0.0001 for all).
      Other independent predictors of lower haemoglobin were older age, female gender
      and lower eGFR. CONCLUSIONS: Our findings suggest that increased plasma hs-CRP
      concentrations are independently associated with anaemia in the setting of
      decreased kidney function in a large cohort of unselected adult outpatients.

PMID- 18326563
TI  - Silencing genes in the kidney: antisense or RNA interference?

PMID- 18326564
TI  - Resolution of SLE-related soft-tissue calcification following haematopoietic stem
      cell transplantation.
AB  - BACKGROUND: Calciphylaxis and calcinosis can both cause severe morbidity and
      mortality in patients with systemic lupus erythematosus (SLE). Haematopoietic
      stem cell transplantation (HSCT) has been successfully used to treat patients
      with refractory SLE. It was hypothesized that in calciphylaxis and calcinosis,
      ongoing inflammatory activity contributes to the calcium deposition in the media
      of small arteries, as well as perivascular and periarticular tissues. We report
      three patients whose soft-tissue calcification syndromes dramatically resolved
      after undergoing HSCT. METHODS: Three patients referred for refractory SLE
      underwent HSCT at a tertiary care medical center. SLE serologies and clinical
      features before and after HSCT were recorded. RESULTS: Despite receiving >6
      months of intravenous cyclophosphamide (CYC), three SLE patients showed signs of
      persistent lupus activity, including severe soft-tissue calcification. The first
      patient was on haemodialysis and developed severe calciphylaxis with large ulcers
      and tissue necrosis. The second patient had calcinosis, with palpable crystals
      extruding from ulcers. The third patient had calcinosis characterized by
      subcutaneous nodules and plaques. Because prior conventional therapies had
      failed, the three were treated with high-dose CYC, anti-thymocyte globulin and
      HSCT. They have been followed post-HSCT for 26-38 months, with excellent clinical
      responses, including sustained resolution of skin abnormalities. CONCLUSIONS: The
      successful treatment of advanced calcium deposition by aggressive immune ablation
      underscores the contribution of SLE-mediated inflammation to soft-tissue
      calcification syndromes.

PMID- 18326565
TI  - Glutamate metabolism in Bacillus subtilis: gene expression and enzyme activities
      evolved to avoid futile cycles and to allow rapid responses to perturbations of
      the system.
AB  - Glutamate is a central metabolite in all organisms since it provides the link
      between carbon and nitrogen metabolism. In Bacillus subtilis, glutamate is
      synthesized exclusively by the glutamate synthase, and it can be degraded by the
      glutamate dehydrogenase. In B. subtilis, the major glutamate dehydrogenase RocG
      is expressed only in the presence of arginine, and the bacteria are unable to
      utilize glutamate as the only carbon source. In addition to rocG, a second
      cryptic gene (gudB) encodes an inactive glutamate dehydrogenase. Mutations in
      rocG result in the rapid accumulation of gudB1 suppressor mutations that code for
      an active enzyme. In this work, we analyzed the physiological significance of
      this constellation of genes and enzymes involved in glutamate metabolism. We
      found that the weak expression of rocG in the absence of the inducer arginine is
      limiting for glutamate utilization. Moreover, we addressed the potential ability
      of the active glutamate dehydrogenases of B. subtilis to synthesize glutamate.
      Both RocG and GudB1 were unable to catalyze the anabolic reaction, most probably
      because of their very high K(m) values for ammonium. In contrast, the Escherichia
      coli glutamate dehydrogenase is able to produce glutamate even in the background
      of a B. subtilis cell. B. subtilis responds to any mutation that interferes with
      glutamate metabolism with the rapid accumulation of extragenic or intragenic
      suppressor mutations, bringing the glutamate supply into balance. Similarly, with
      the presence of a cryptic gene, the system can flexibly respond to changes in the
      external glutamate supply by the selection of mutations.

PMID- 18326566
TI  - IS6110, a Mycobacterium tuberculosis complex-specific insertion sequence, is also
      present in the genome of Mycobacterium smegmatis, suggestive of lateral gene
      transfer among mycobacterial species.
AB  - IS6110 is an insertion element found exclusively within the members of the
      Mycobacterium tuberculosis complex (MTBC), and because of this exclusivity, it
      has become an important diagnostic tool in the identification of MTBC species.
      The restriction of IS6110 to the MTBC is hypothesized to arise from the inability
      of these bacteria to exchange DNA. We have identified an IS6110-related element
      in a strain of Mycobacterium smegmatis. The presence of IS6110 indicates that
      lateral gene transfer has occurred among mycobacterial species, suggesting that
      the mycobacterial gene pool is larger than previously suspected.

PMID- 18326567
TI  - A new lineage of halophilic, wall-less, contractile bacteria from a brine-filled
      deep of the Red Sea.
AB  - A novel strictly anaerobic bacterium designated strain SSD-17B(T) was isolated
      from the hypersaline brine-sediment interface of the Shaban Deep, Red Sea. Cells
      were pleomorphic but usually consisted of a central coccoid body with one or two
      "tentacle-like" protrusions. These protrusions actively alternated between a
      straight, relaxed form and a contracted, corkscrew-like one. A peptidoglycan
      layer was not detected by electron microscopy. The organism forms "fried-egg"
      like colonies on MM-X medium. The organism is strictly anaerobic and halophilic
      and has an optimum temperature for growth of about 30 to 37 degrees C and an
      optimum pH of about 7. Nitrate and nitrite are reduced; lactate is a fermentation
      product. The fatty acid profile is dominated by straight saturated and
      unsaturated chain compounds. Menaquinone 4 is the major respiratory quinone.
      Phylogenetic analysis demonstrated strain SSD-17B(T) represents a novel and
      distinct lineage within the radiation of the domain Bacteria. The branching
      position of strain SSD-17B(T) was equidistant to the taxa considered to be
      representative lineages of the phyla Firmicutes and Tenericutes (with its sole
      class Mollicutes). The phenotypic and phylogenetic data clearly show the
      distinctiveness of this unusual bacterium, and we therefore propose that strain
      SSD-17B(T) (= DSM 18853 = JCM 14575) represents a new genus and a new species,
      for which we recommend the name Haloplasma contractile gen. nov., sp. nov. We are
      also of the opinion that the organism represents a new order-level taxon, for
      which we propose the name Haloplasmatales.

PMID- 18326568
TI  - ATP-induced shrinkage of DNA with MukB protein and the MukBEF complex of
      Escherichia coli.
AB  - Fluorescence microscopic observation of individual T4 DNA molecules revealed that
      the MukBEF complex (bacterial condensin) and its subunit, the MukB (a member of
      the SMC [structural maintenance of chromosomes] superfamily) homodimer, of
      Escherichia coli markedly shrunk large DNA molecules in the presence of
      hydrolyzable ATP. In contrast, in the presence of ADP or ATP-gammaS, the
      conformation of DNA was almost not changed. This suggests that the ATPase
      activity of subunit MukB is essential for shrinking large DNA molecules.
      Stretching experiments on the shrunken DNA molecules in the presence of ATP and
      MukBEF indicated a cross-bridging interaction between DNA molecules.

PMID- 18326569
TI  - Enterococcus faecalis PcfC, a spatially localized substrate receptor for type IV
      secretion of the pCF10 transfer intermediate.
AB  - Upon sensing of peptide pheromone, Enterococcus faecalis efficiently transfers
      plasmid pCF10 through a type IV secretion (T4S) system to recipient cells. The
      PcfF accessory factor and PcfG relaxase initiate transfer by catalyzing strand
      specific nicking at the pCF10 origin of transfer sequence (oriT). Here, we
      present evidence that PcfF and PcfG spatially coordinate docking of the pCF10
      transfer intermediate with PcfC, a membrane-bound putative ATPase related to the
      coupling proteins of gram-negative T4S machines. PcfC and PcfG fractionated with
      the membrane and PcfF with the cytoplasm, yet all three proteins formed several
      punctate foci at the peripheries of pheromone-induced cells as monitored by
      immunofluorescence microscopy. A PcfC Walker A nucleoside triphosphate (NTP)
      binding site mutant (K156T) fractionated with the E. faecalis membrane and also
      formed foci, whereas PcfC deleted of its N-terminal putative transmembrane domain
      (PcfCDelta N103) distributed uniformly throughout the cytoplasm. Native PcfC and
      mutant proteins PcfCK156T and PcfCDelta N103 bound pCF10 but not pcfG or Delta
      oriT mutant plasmids as shown by transfer DNA immunoprecipitation, indicating
      that PcfC binds only the processed form of pCF10 in vivo. Finally, purified
      PcfCDelta N103 bound DNA substrates and interacted with purified PcfF and PcfG in
      vitro. Our findings support a model in which (i) PcfF recruits PcfG to oriT to
      catalyze T-strand nicking, (ii) PcfF and PcfG spatially position the relaxosome
      at the cell membrane to stimulate substrate docking with PcfC, and (iii) PcfC
      initiates substrate transfer through the pCF10 T4S channel by an NTP-dependent
      mechanism.

PMID- 18326570
TI  - Structural analysis and biosynthesis gene cluster of an antigenic
      glycopeptidolipid from Mycobacterium intracellulare.
AB  - Mycobacterium avium-Mycobacterium intracellulare complex (MAC) is the most common
      isolate of nontuberculous mycobacteria and causes pulmonary and extrapulmonary
      diseases. MAC species can be grouped into 31 serotypes by the epitopic
      oligosaccharide structure of the species-specific glycopeptidolipid (GPL)
      antigen. The GPL consists of a serotype-common fatty acyl peptide core with 3,4
      di-O-methyl-rhamnose at the terminal alaninol and a 6-deoxy-talose at the allo
      threonine and serotype-specific oligosaccharides extending from the 6-deoxy
      talose. Although the complete structures of 15 serotype-specific GPLs have been
      defined, the serotype 16-specific GPL structure has not yet been elucidated. In
      this study, the chemical structure of the serotype 16 GPL derived from M.
      intracellulare was determined by using chromatography, mass spectrometry, and
      nuclear magnetic resonance analyses. The result indicates that the terminal
      carbohydrate epitope of the oligosaccharide is a novel N-acyl-dideoxy-hexose. By
      the combined linkage analysis, the oligosaccharide structure of serotype 16 GPL
      was determined to be 3-2'-methyl-3'-hydroxy-4'-methoxy-pentanoyl-amido-3,6
      dideoxy-beta-hexose-(1-->3)-4-O-methyl-alpha-L-rhamnose-(1-->3)-alpha-L-rhamnose
      (1-->3)-alpha-L-rhamnose-(1-->2)-6-deoxy-alpha-L-talose. Next, the 22.9-kb
      serotype 16-specific gene cluster involved in the glycosylation of
      oligosaccharide was isolated and sequenced. The cluster contained 17 open reading
      frames (ORFs). Based on the similarity of the deduced amino acid sequences, it
      was assumed that the ORF functions include encoding three glycosyltransferases,
      an acyltransferase, an aminotransferase, and a methyltransferase. An M. avium
      serotype 1 strain was transformed with cosmid clone no. 253 containing gtfB-drrC
      of M. intracellulare serotype 16, and the transformant produced serotype 16 GPL.
      Together, the ORFs of this serotype 16-specific gene cluster are responsible for
      the biosynthesis of serotype 16 GPL.

PMID- 18326571
TI  - Quantitative analysis of three hydrogenotrophic microbial groups, methanogenic
      archaea, sulfate-reducing bacteria, and acetogenic bacteria, within plaque
      biofilms associated with human periodontal disease.
AB  - Human subgingival plaque biofilms are highly complex microbial ecosystems that
      may depend on H(2)-metabolizing processes. Here we investigated the ubiquity and
      proportions of methanogenic archaea, sulfate reducers, and acetogens in plaque
      samples from 102 periodontitis patients. In contrast to the case for 65 healthy
      control subjects, hydrogenotrophic groups were almost consistently detected in
      periodontal pockets, with the proportions of methanogens and sulfate reducers
      being significantly elevated in severe cases. In addition, antagonistic
      interactions among the three microbial groups indicated that they may function as
      alternative syntrophic partners of secondary fermenting periodontal pathogens.

PMID- 18326572
TI  - Topology and function of CcmD in cytochrome c maturation.
AB  - The system I cytochrome c biogenesis pathway requires CcmD, a small polypeptide
      of 69 residues in Escherichia coli. Here it is shown that CcmD is a component of
      the CcmABC ATP-binding cassette transporter complex. CcmD is not necessary for
      the CcmC-dependent transfer of heme to CcmE in the periplasm or for interaction
      of CcmE with CcmABC. CcmD is absolutely required for the release of holo-CcmE
      from the CcmABCD complex. Evidence is presented that the topology of CcmD in the
      cytoplasmic membrane is the N terminus outside and the C terminus inside with one
      transmembrane domain.

PMID- 18326573
TI  - Influence of the sigmaB stress factor and yxaB, the gene for a putative
      exopolysaccharide synthase under sigmaB Control, on biofilm formation.
AB  - Bacillus subtilis forms structured communities of biofilms encased in an
      exopolysaccharide matrix on solid surfaces and at the air-liquid interface. It is
      postulated that nonoptimal growth conditions induce this multicellular behavior.
      We showed that under laboratory conditions a strain deleted for sigB was unable
      to form a floating pellicle on the surface of a liquid medium. However,
      overexpression of yxaB, encoding a putative exopolysaccharide synthase, from a
      p(Spac) promoter in a sigB-deleted strain resulted in partial recovery of the
      wild-type phenotype, indicating the participation of the YxaB protein in this
      multicellular process. We present data concerning the regulation of transcription
      of genes yxaB and yxaA, encoding a putative glycerate kinase. Both genes are
      cotranscribed as a single transcription unit from a sigma(A)-dependent promoter
      during vegetative growth of a liquid bacterial culture. The promoter driving
      transcription of the yxaAB operon is regulated by AbrB. In addition, the second
      gene in the operon, yxaB, possesses its own promoter, which is recognized by RNA
      polymerase containing the sigma(B) subunit. This transcription start site is used
      under general stress conditions, resulting in increased expression.

PMID- 18326574
TI  - ORF334 in Vibrio phage KVP40 plays the role of gp27 in T4 phage to form a
      heterohexameric complex.
AB  - KVP40 is a T4-related phage, composed of 386 open reading frames (ORFs), that has
      a broad host range. Here, we overexpressed, purified, and biophysically
      characterized two of the proteins encoded in the KVP40 genome, namely, gp5 and
      ORF334. Homology-based comparison between KVP40 and its better-characterized
      sister phage, T4, was used to estimate the two KVP40 proteins' functions. KVP40
      gp5 shared significant homology with T4 gp5 in the N- and C-terminal domains.
      Unlike T4 gp5, KVP40 gp5 lacked the internal lysozyme domain. Like T4 gp5, KVP40
      gp5 was found to form a homotrimer in solution. In stark contrast, KVP40 ORF334
      shared no significant homology with any known proteins from T4-related phages.
      KVP40 ORF334 was found to form a heterohexamer with KVP40 gp5 in solution in a
      fashion nearly identical to the interaction between the T4 gp5 and gp27 proteins.
      Electron microscope image analysis of the KVP40 gp5-ORF334 complex indicated that
      it had dimensions very similar to those of the T4 gp5-gp27 structure. On the
      basis of our biophysical characterization, along with positional genome
      information, we propose that ORF334 is the ortholog of T4 gp27 and that it plays
      the role of a linker between gp5 and the phage baseplate.

PMID- 18326575
TI  - RcoM: a new single-component transcriptional regulator of CO metabolism in
      bacteria.
AB  - Genomic analysis suggested the existence of a CO-sensing bacterial
      transcriptional regulator that couples an N-terminal PAS fold domain to a C
      terminal DNA-binding LytTR domain. UV/visible-light spectral analyses of
      heterologously expressed, purified full-length proteins indicated that they
      contained a hexacoordinated b-type heme moiety that avidly binds CO and NO.
      Studies of protein variants strongly suggested that the PAS domain residues His74
      and Met104 serve as the heme Fe(II) axial ligands, with displacement of Met104
      upon binding of the gaseous effectors. Two RcoM (regulator of CO metabolism)
      homologs were shown to function in vivo as CO sensors capable of regulating an
      aerobic CO oxidation (cox) regulon. The genetic linkage of rcoM with both aerobic
      (cox) and anaerobic (coo) CO oxidation systems suggests that in different
      organisms RcoM proteins may control either regulon type.

PMID- 18326576
TI  - Staphylococcus aureus HrtA is an ATPase required for protection against heme
      toxicity and prevention of a transcriptional heme stress response.
AB  - During systemic infection, Staphylococcus aureus acquires nutrient iron from
      heme, the cofactor of vertebrate myoglobin and hemoglobin. Upon exposure to heme,
      S. aureus up-regulates the expression of the heme-regulated transporter, HrtAB.
      Strains lacking hrtAB exhibit increased sensitivity to heme toxicity, and upon
      heme exposure they elaborate a secreted protein response that interferes with the
      recruitment of neutrophils to the site of infection. Taken together, these
      results have led to the suggestion that hrtAB encodes an efflux system
      responsible for relieving the toxic effects of accumulated heme. Here we extend
      these observations by demonstrating that HrtA is the ATPase component of the
      HrtAB transport system. We show that HrtA is an Mn(2+)/Mg(2+)-dependent ATPase
      that functions at an optimal pH of 7.5 and exhibits in vitro temperature
      dependence uncommon to ABC transporter ATPases. Furthermore, we identify
      conserved residues within HrtA that are required for in vitro ATPase activity and
      are essential for the functionality of HrtA in vivo. Finally, we show that heme
      induces an alteration in the gene expression pattern of S. aureus Delta hrtA,
      implying the presence of a novel transcriptional regulatory mechanism responsible
      for the previously described immunomodulatory characteristics of hrtA mutants
      exposed to heme.

PMID- 18326577
TI  - Phenolic acid-mediated regulation of the padC gene, encoding the phenolic acid
      decarboxylase of Bacillus subtilis.
AB  - In Bacillus subtilis, several phenolic acids specifically induce expression of
      padC, encoding a phenolic acid decarboxylase that converts these antimicrobial
      compounds into vinyl derivatives. padC forms an operon with a putative coding
      sequence of unknown function, yveFG, and this coding sequence does not appear to
      be involved in the phenolic acid stress response (PASR). To identify putative
      regulators involved in the PASR, random transposon mutagenesis, combined with two
      different screens, was performed. PadR, a negative transcriptional regulator of
      padC expression, was identified. padR is not located in the vicinity of padC, and
      the expression of padR is low and appears constitutive. This is in contrast with
      what occurs in other gram-positive bacteria, in which padR is autoregulated and
      induced by phenolic acids. Further screening of the transposon library failed to
      identify genes other than padR involved in the PASR. Modest inactivation of padR
      by phenolic acids was obtained in recombinant Escherichia coli expressing padC
      and padR, and this translates into induction of decarboxylase activity. Gel shift
      promoter binding assays performed with and without MgCl(2), and with and without
      phenolic acids, demonstrated that phenolic acids were able to abolish the binding
      of PadR to the yveFG-padC promoter in the absence of MgCl(2). Altogether, our
      results indicate that (i) PadR is inactivated directly by phenolic acids in
      vitro, (ii) inhibition of PadR in response to phenolic acids may occur without
      the need for a sensor-like effector in B. subtilis, and (iii) phenolic acids are
      able to modulate PadR activity in E. coli in the absence of any additional
      effector.

PMID- 18326578
TI  - Characterization of the Streptomyces lividans PspA response.
AB  - Phage shock protein (Psp) is induced by extracytoplasmic stress that may reduce
      the energy status of the cell. It is encoded in Escherichia coli by the phage
      shock protein regulon consisting of pspABCDE and by pspF and pspG. The phage
      shock protein system is highly conserved among a large number of gram-negative
      bacteria. However, many bacterial genomes contain only a pspA homologue but no
      homologues of the other genes of the Psp system. This conservation indicates that
      PspA alone might play an important role in these bacteria. In Streptomyces
      lividans, a soil-borne gram-positive bacterium, the phage shock protein system
      consists only of the pspA gene. In this report, we showed that pspA encodes a 28
      kDa protein that is present in both the cytoplasmic and the membrane fractions of
      the S. lividans mycelium. We demonstrated that the pspA gene is strongly induced
      under stress conditions that attack membrane integrity and that it is essential
      for growth and survival under most of these conditions. The data reported here
      clearly show that PspA plays an important role in S. lividans under stress
      conditions despite the absence of other psp homologues, suggesting that PspA may
      be more important in most bacteria than previously thought.

PMID- 18326579
TI  - Genomic and functional analysis of ICEPdaSpa1, a fish-pathogen-derived SXT
      related integrating conjugative element that can mobilize a virulence plasmid.
AB  - Integrating conjugative elements (ICEs) are self-transmissible mobile elements
      that transfer between bacteria via conjugation and integrate into the host
      chromosome. SXT and related ICEs became prevalent in Asian Vibrio cholerae
      populations in the 1990s and play an important role in the dissemination of
      antibiotic resistance genes in V. cholerae. Here, we carried out genomic and
      functional analyses of ICEPdaSpa1, an SXT-related ICE derived from a Spanish
      isolate of Photobacterium damselae subsp. piscicida, the causative agent of fish
      pasteurellosis. The approximately 102-kb DNA sequence of ICEPdaSpa1 shows nearly
      97% DNA sequence identity to SXT in genes that encode essential ICE functions,
      including integration and excision, conjugal transfer, and regulation. However,
      approximately 25 kb of ICEPdaSpa1 DNA, including a tetracycline resistance locus,
      is not present in SXT. Most ICEPdaSpa1-specific DNA is inserted at loci where
      other SXT-related ICEs harbor element-specific DNA. ICEPdaSpa1 excises itself
      from the chromosome and is transmissible to other Photobacterium strains, as well
      as to Escherichia coli, in which it integrates into prfC. Interestingly, the P.
      damselae virulence plasmid pPHDP10 could be mobilized from E. coli in an
      ICEPdaSpa1-dependent fashion via the formation of a cointegrate between pPHDP10
      and ICEPdaSpa1. pPHDP10-Cm integrated into ICEPdaSpa1 in a non-site-specific
      fashion independently of RecA. The ICEPdaSpa1::pPHDP10 cointegrates were stable,
      and markers from both elements became transmissible at frequencies similar to
      those observed for the transfer of ICEPdaSpa1 alone. Our findings reveal the
      plasticity of ICE genomes and demonstrate that ICEs can enable virulence gene
      transfer.

PMID- 18326580
TI  - The legacy of HfrH: mutations in the two-component system CreBC are responsible
      for the unusual phenotype of an Escherichia coli arcA mutant.
AB  - Strains derived from HfrH carrying the arcA2 null mutation exhibit a higher
      respiratory rate, enhanced glucose consumption, and a more-reduced intracellular
      redox state than arcA deletion mutants of a different lineage. The phenotype of
      the arcA2 mutants was due to the presence of a creC constitutive mutation
      introduced by P1 transduction.

PMID- 18326581
TI  - RhlA converts beta-hydroxyacyl-acyl carrier protein intermediates in fatty acid
      synthesis to the beta-hydroxydecanoyl-beta-hydroxydecanoate component of
      rhamnolipids in Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa secretes a rhamnolipid (RL) surfactant that functions in
      hydrophobic nutrient uptake, swarming motility, and pathogenesis. We show that
      RhlA supplies the acyl moieties for RL biosynthesis by competing with the enzymes
      of the type II fatty acid synthase (FASII) cycle for the beta-hydroxyacyl-acyl
      carrier protein (ACP) pathway intermediates. Purified RhlA forms one molecule of
      beta-hydroxydecanoyl-beta-hydroxydecanoate from two molecules of beta
      hydroxydecanoyl-ACP and is the only enzyme required to generate the lipid
      component of RL. The acyl groups in RL are primarily beta-hydroxydecanoyl, and in
      vitro, RhlA has a greater affinity for 10-carbon substrates, illustrating that
      RhlA functions as a molecular ruler that selectively extracts 10-carbon
      intermediates from FASII. Eliminating either FabA or FabI activity in P.
      aeruginosa increases RL production, illustrating that slowing down FASII allows
      RhlA to more-effectively compete for beta-hydroxydecanoyl-ACP. In Escherichia
      coli, the rate of fatty acid synthesis increases 1.3-fold when RhlA is expressed,
      to ensure the continued formation of fatty acids destined for membrane
      phospholipid even though 24% of the carbon entering FASII is diverted to RL
      synthesis. Previous studies have placed a ketoreductase, called RhlG, before RhlA
      in the RL biosynthetic pathway; however, our experiments show that RhlG has no
      role in RL biosynthesis. We conclude that RhlA is necessary and sufficient to
      form the acyl moiety of RL and that the flux of carbon through FASII accelerates
      to support RL production and maintain a supply of acyl chains for phospholipid
      synthesis.

PMID- 18326582
TI  - Roles of charged residues in the C-terminal region of PomA, a stator component of
      the Na+-driven flagellar motor.
AB  - Bacterial flagellar motors use specific ion gradients to drive their rotation. It
      has been suggested that the electrostatic interactions between charged residues
      of the stator and rotor proteins are important for rotation in Escherichia coli.
      Mutational studies have indicated that the Na(+)-driven motor of Vibrio
      alginolyticus may incorporate interactions similar to those of the E. coli motor,
      but the other electrostatic interactions between the rotor and stator proteins
      may occur in the Na(+)-driven motor. Thus, we investigated the C-terminal charged
      residues of the stator protein, PomA, in the Na(+)-driven motor. Three of eight
      charge-reversing mutations, PomA(K203E), PomA(R215E), and PomA(D220K), did not
      confer motility either with the motor of V. alginolyticus or with the Na(+)
      driven chimeric motor of E. coli. Overproduction of the R215E and D220K mutant
      proteins but not overproduction of the K203E mutant protein impaired the motility
      of wild-type V. alginolyticus. The R207E mutant conferred motility with the motor
      of V. alginolyticus but not with the chimeric motor of E. coli. The motility with
      the E211K and R232E mutants was similar to that with wild-type PomA in V.
      alginolyticus but was greatly reduced in E. coli. Suppressor analysis suggested
      that R215 may participate in PomA-PomA interactions or PomA intramolecular
      interactions to form the stator complex.

PMID- 18326583
TI  - Topological mapping of the asymmetric drug binding to the human ether-a-go-go
      related gene product (HERG) potassium channel by use of tandem dimers.
AB  - The human ether-a-go-go related gene product (HERG) channel is essential for
      electrical activity of heart cells, and block of this channel by many drugs leads
      to lethal arrhythmias. Tyr(652) and Phe(656) of the sixth transmembrane helix are
      candidates for the drug binding site. In the tetrameric HERG channel, a drug with
      asymmetric structure should interact unevenly with multiple residues from
      different subunits. To elucidate the topology of the drug-binding site, we
      constructed tandem dimers of HERG channels and the aromatic Tyr(652) and Phe(656)
      residues were replaced by alanine singly or doubly. Eight types of HERG channels,
      including homotetrameric mutants, having different numbers and arrangements of
      aromatic residues at the blocking site, were studied. Effects of cisapride on
      channels expressed in Xenopus laevis oocytes were examined
      electrophysiologically. The inhibition constants (K(i)) were increased
      significantly as the diagonal Tyr(652) were deleted, whereas those for the
      diagonal Phe(656)-deleted mutant were not changed. These results suggest that
      Tyr(652) residues from adjacent subunits contributed to the binding. Two types of
      double mutants of tandem dimers showed significantly distinct affinities,
      suggesting that the coexistence of Tyr(652) and Phe(656) on a subunit in diagonal
      position is crucial to having a high affinity. Thermodynamic double-mutant cycle
      analyses revealed interactions between Tyr(652) and Phe(656) upon binding. The
      kinetics and voltage-dependence of blocking suggested transitions of the binding
      site from low to high affinity. These approaches using a set of mutant HERG
      channels gave a dynamic picture of the spatial arrangements of residues that
      contribute to the drug-channel interaction.

PMID- 18326584
TI  - Making the T-type even tinier: corticotropin-releasing factor-mediated inhibition
      of low-voltage-activated calcium channel activity.
AB  - T-type calcium channels are important for a variety of physiological processes
      such as brain and heart function. Proper regulation of these channels by second
      messengers is fundamental; however, our knowledge of the molecular pathways that
      regulate T-type calcium channels is limited in comparison with other voltage
      dependent calcium channels. In this issue of Molecular Pharmacology, Tao et al.
      (p. 1596) demonstrate that Cav3.2 is regulated by activation of the corticotropin
      releasing factor receptor 1 in a Gbetagamma-dependent manner.

PMID- 18326585
TI  - Dictyostelium Aurora kinase has properties of both Aurora A and Aurora B kinases.
AB  - Aurora kinases are highly conserved proteins with important roles in mitosis.
      Metazoans contain two kinases, Aurora A and B, which contribute distinct
      functions at the spindle poles and the equatorial region respectively. It is not
      currently known whether the specialized functions of the two kinases arose after
      their duplication in animal cells or were already present in their ancestral
      kinase. We show that Dictyostelium discoideum contains a single Aurora kinase,
      DdAurora, that displays characteristics of both Aurora A and B. Like Aurora A,
      DdAurora has an extended N-terminal domain with an A-box sequence and localizes
      at the spindle poles during early mitosis. Like Aurora B, DdAurora binds to its
      partner DdINCENP and localizes on centromeres at metaphase, the central spindle
      during anaphase, and the cleavage furrow at the end of cytokinesis. DdAurora also
      has several unusual properties. DdAurora remains associated with centromeres in
      anaphase, and this association does not require an interaction with DdINCENP.
      DdAurora then localizes at the cleavage furrow, but only at the end of
      cytokinesis. This localization is dependent on DdINCENP and the motor proteins
      Kif12 and myosin II. Thus, DdAurora may represent the ancestral kinase that gave
      rise to the different Aurora kinases in animals and also those in other
      organisms.

PMID- 18326586
TI  - Role of PUG1 in inducible porphyrin and heme transport in Saccharomyces
      cerevisiae.
AB  - Unlike pathogenic fungi, the budding yeast Saccharomyces cerevisiae is not
      efficient at using heme as a nutritional source of iron. Here we report that for
      this yeast, heme uptake is induced under conditions of heme starvation. Heme
      synthesis requires oxygen, and yeast grown anaerobically exhibited an increased
      uptake of hemin. Similarly, a strain lacking aminolevulinate synthase exhibited a
      sixfold increase in hemin uptake when grown without 2-aminolevulinic acid. We
      used microarray analysis of cells grown under reduced oxygen tension or reduced
      intracellular heme conditions to identify candidate genes involved in heme
      uptake. Surprisingly, overexpression of PUG1 (protoporphyrin uptake gene 1)
      resulted in reduced utilization of exogenous heme by a heme-deficient strain and,
      conversely, increased the utilization of protoporphyrin IX. Pug1p was localized
      to the plasma membrane by indirect immunofluorescence and subcellular
      fractionation. Strains overexpressing PUG1 exhibited decreased accumulation of
      [(55)Fe]hemin but increased accumulation of protoporphyrin IX compared to the
      wild-type strain. To measure the effect of PUG1 overexpression on intracellular
      heme pools, we used a CYC1-lacZ reporter, which is activated in the presence of
      heme, and we monitored the activity of a heme-containing metalloreductase, Fre1p,
      expressed from a constitutive promoter. The data from these experiments were
      consistent with a role for Pug1p in inducible protoporphyrin IX influx and heme
      efflux.

PMID- 18326587
TI  - Ruminant or industrial sources of trans fatty acids: public health issue or food
      label skirmish?

PMID- 18326588
TI  - Is folic acid good for everyone?
AB  - Fortification of food with folic acid to reduce the number of neural tube defects
      was introduced 10 y ago in North America. Many countries are considering whether
      to adopt this policy. When fortification is introduced, several hundred thousand
      people are exposed to an increased intake of folic acid for each neural tube
      defect pregnancy that is prevented. Are the benefits to the few outweighed by
      possible harm to some of the many exposed? In animals, a folic acid-rich diet can
      influence DNA and histone methylation, which leads to phenotypic changes in
      subsequent generations. In humans, increased folic acid intake leads to elevated
      blood concentrations of naturally occurring folates and of unmetabolized folic
      acid. High blood concentrations of folic acid may be related to decreased natural
      killer cell cytotoxicity, and high folate status may reduce the response to
      antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and
      cancer. In the elderly, a combination of high folate levels and low vitamin B-12
      status may be associated with an increased risk of cognitive impairment and
      anemia and, in pregnant women, with an increased risk of insulin resistance and
      obesity in their children. Folate has a dual effect on cancer, protecting against
      cancer initiation but facilitating progression and growth of preneoplastic cells
      and subclinical cancers, which are common in the population. Thus, a high folic
      acid intake may be harmful for some people. Nations considering fortification
      should be cautious and stimulate further research to identify the effects, good
      and bad, caused by a high intake of folic acid from fortified food or dietary
      supplements. Only then can authorities develop the right strategies for the
      population as a whole.

PMID- 18326589
TI  - Early differences in fecal microbiota composition in children may predict
      overweight.
AB  - BACKGROUND: Experimental studies suggest that gut microbiota deviations
      predispose toward energy storage and obesity. OBJECTIVE: We wanted to establish
      whether early gut microbiota composition can guide weight development throughout
      early childhood. DESIGN: Overweight and obese children (n = 25) were selected
      from a prospective follow-up study at the age of 7 y and identified according to
      the International Obesity Task Force criteria. Normal-weight children (n = 24)
      were selected from the same cohort and matched for gestational age and body mass
      index at birth, mode of delivery, probiotic supplementation, duration of
      breastfeeding, use of antibiotics during infancy, and frequencies of atopic
      diseases and atopic sensitization. Early fecal microbiota composition was
      analyzed by fluorescent in situ hybridization (FISH) with microscopic and flow
      cytometry detection and by quantitative real-time polymerase chain reaction (qRT
      PCR). RESULTS: The bifidobacterial numbers in fecal samples during infancy, as
      assessed by the FISH with flow cytometry, were higher in children remaining
      normal weight, [median: 2.19 x 10(9) cells/g (interquartile range: 1.10-5.28 x
      10(9) cells/g)] than in children becoming overweight [1.20 x 10(9) cells/g (0.48
      1.59x 10(9) cells/g); P = 0.02]. A similar tendency was found by FISH with
      microscopic detection and qRT-PCR. The microbiota aberrancy during infancy in
      children becoming overweight was also associated with a greater number of
      Staphylococcus aureus [0.64 x 10(6) cells/g (0.33-1.00 x 10(6) cells/g)] than in
      children remaining normal weight [0.27 x 10(6) cells/g (0.17-0.50 x 10(6)
      cells/g); P = 0.013]. CONCLUSION: Aberrant compositional development of the gut
      microbiota precedes overweight, offering new possibilities for preventive and
      therapeutic applications in weight management.

PMID- 18326590
TI  - Immune function and leukocyte sequestration under the influence of parenteral
      lipid emulsions in healthy humans: a placebo-controlled crossover study.
AB  - BACKGROUND: It remains unclear whether immune modulation by lipids contributes to
      the high risk of infectious complications that is associated with the use of
      parenteral nutrition. Although mixed long- and medium-chain triacylglycerol (LCT
      MCT)-containing emulsions, but not pure LCT emulsions, activate neutrophils and
      impair crucial leukocyte functions in vitro, in vivo studies have failed to
      corroborate these findings. OBJECTIVES: The present investigation was conducted
      to evaluate the effects of LCT and LCT-MCT on immune function in healthy humans
      and to assess whether the lack of in vivo effects results from sampling errors
      due to extravascular sequestration of activated neutrophils. DESIGN: Saline, LCT
      MCT, and LCT emulsions were administered intravenously for 4.5 h to 12 healthy
      volunteers in a randomized crossover design. Plasma triacylglycerol
      concentrations were clamped at a clinically relevant concentration of 3-5 mmol/L.
      Leukocyte population counts and neutrophil activation were assessed before and
      after infusion. Leukocyte sequestration was evaluated by monitoring the
      distribution of Technetium-99m-labeled autologous leukocytes during infusions.
      RESULTS: Whereas LCT exerted no greater effects than did saline, LCT-MCT
      significantly decreased lymphocyte counts. However, no evidence for neutrophil
      activation was found with either lipid. Moreover, the clearance of radiolabeled
      leukocytes from the liver, spleen, and lungs was not altered by any lipid, which
      suggested that lipid emulsions do not induce leukocyte sequestration.
      CONCLUSIONS: Short-term infusion of LCT-MCT (but not LCT) to healthy humans
      modulates leukocyte population counts but, in clear contrast with the in vitro
      situation, does not induce neutrophil activation. These disparate findings cannot
      be explained by MCT-induced leukocyte sequestration.

PMID- 18326591
TI  - Essential n-3 fatty acids in pregnant women and early visual acuity maturation in
      term infants.
AB  - BACKGROUND: Docosahexaenoic acid (DHA) is important to neural development.
      Whether DHA intakes are low enough in some pregnant women to impair infant
      development is uncertain. OBJECTIVE: We sought to determine whether DHA
      deficiency occurs in pregnant women and contributes to poor infant development.
      DESIGN: Biochemical cutoffs, dietary intakes, or developmental scores indicative
      of DHA deficiency are not defined. Infant development has a distribution in which
      an individual's potential development is unknown. This was a randomized
      intervention to establish a distribution of developmental scores for infants of
      women with DHA intakes considered to be above requirements against which to
      compare the development of infants of mothers consuming their usual diet. DHA
      (400 mg/d; n = 67) or a placebo (n = 68) was consumed by the women from 16 wk
      gestation until delivery. We determined maternal red blood cell ethanolamine
      phosphoglyceride fatty acids, dietary intakes at 16 and 36 wk gestation, and
      infant visual acuity at 60 d of age. RESULTS: We described an approach to
      identify DHA deficiency when biochemical and functional markers of deficiency are
      unknown. In multivariate analyses, infant visual acuity was related to sex (beta
      = 0.660, SE = 0.93, and odds ratio = 1.93) and maternal DHA intervention (beta =
      1.215, SE = 1.64, and odds ratio = 3.37). More infant girls in the placebo than
      in the DHA intervention group had a visual acuity below average (P = 0.048).
      Maternal red blood cell ethanolamine phosphoglyceride docosatetraenoic acid was
      inversely related to visual acuity in boys (rho = -0.37, P < 0.05) and girls (rho
      = -0.48, P < 0.01). CONCLUSIONS: These studies suggest that some pregnant women
      in our study population were DHA-deficient.

PMID- 18326592
TI  - Do trans fatty acids from industrially produced sources and from natural sources
      have the same effect on cardiovascular disease risk factors in healthy subjects?
      Results of the trans Fatty Acids Collaboration (TRANSFACT) study.
AB  - BACKGROUND: The consumption of monounsaturated trans fatty acids (TFAs) increases
      the risk of cardiovascular disease (CVD). Putative differences between the
      effects of TFAs from industrially produced and natural sources on CVD risk
      markers were not previously investigated in healthy subjects. OBJECTIVE: We aimed
      to compare the effects of TFAs from industrially produced and natural sources on
      HDL and LDL cholesterol, lipoprotein particle size and distribution,
      apolipoproteins, and other lipids in healthy subjects. DESIGN: In a randomized,
      double-blind, controlled, crossover design, 46 healthy subjects (22 men and 24
      women) consumed food items containing TFAs (11-12 g/d, representing approximately
      5% of daily energy) from the 2 sources. RESULTS: Forty subjects (19 men and 21
      women) completed the study. Compared with TFAs from industrially produced
      sources, TFAs from natural sources significantly (P = 0.012) increased HDL
      cholesterol in women but not in men. Significant (P = 0.001) increases in LDL
      cholesterol concentrations were observed in women, but not in men, after the
      consumption of TFAs from natural sources. Apolipoprotein (apo)B and apoA1
      concentrations confirmed the changes observed in LDL and HDL cholesterol.
      Analysis of lipoprotein subclass showed that only large HDL and LDL
      concentrations were modified by TFAs from natural sources but not by those from
      industrially produced sources. CONCLUSIONS: This study shows that TFAs from
      industrially produced and from natural sources have different effects on CVD risk
      factors in women. The HDL cholesterol-lowering property of TFAs seems to be
      specific to industrial sources. However, it is difficult in the present study to
      draw a conclusion about the effect of TFAs from either source on absolute CVD
      risk in these normolipidemic subjects. The mechanism underlying the observed sex-
      and isomer-specific effects warrants further investigation.

PMID- 18326593
TI  - Effects of weight loss from a very-low-carbohydrate diet on endothelial function
      and markers of cardiovascular disease risk in subjects with abdominal obesity.
AB  - BACKGROUND: The effects of a very-low-carbohydrate, high-saturated-fat weight
      loss diet (LC) on brachial artery flow-mediated dilatation (FMD) and markers of
      endothelial function are unknown. OBJECTIVE: The effect of an LC on markers of
      endothelial function and cardiovascular disease (CVD) risk was compared with that
      of an isocaloric high-carbohydrate, low-saturated-fat diet (HC). DESIGN: FMD and
      markers of endothelial function (n = 70) and CVD risk were measured before and
      after 8 wk of weight loss. Ninety-nine subjects aged 50.0 +/- 8.3 y with a body
      mass index (in kg/m2) of 33.7 +/- 4.1 completed the study. RESULTS: Mean (+/-SD)
      FMD did not change significantly (P = 0.55) with either diet. Pulse wave velocity
      improved with both diets (P < 0.01). Endothelial markers, E- and P selectin,
      intracellular and cellular-adhesion molecule-1, tissue-type plasminogen
      activator, and plasminogen activator inhibitor-1 decreased (P < 0.001), with no
      diet effect. Adiponectin did not change significantly. More weight (P = 0.05 for
      diet x time interaction) and more abdominal fat mass (P = 0.05 for diet x time
      interaction) were lost with the LC than with the HC. LDL cholesterol decreased
      more with the HC than with the LC (P < 0.05, time x diet), and C-reactive protein
      decreased more with the HC than with the LC (P < 0.05 for diet x time
      interaction). Homocysteine increased more with the LC (P < 0.01 for diet x time
      interaction). Folate decreased with the LC and increased with the HC (P < 0.05,
      time; P < 0.001 for diet x time interaction). CONCLUSION: An LC does not impair
      FMD. We observed beneficial effects of both diets on most of the CVD risk factors
      measured. This trial was registered with the Australian Clinical Trials Registry
      as ACTR N0 12606000203550.

PMID- 18326594
TI  - Dietary and supplementary betaine: acute effects on plasma betaine and
      homocysteine concentrations under standard and postmethionine load conditions in
      healthy male subjects.
AB  - BACKGROUND: Betaine comes from the diet and from choline, and it is associated
      with vascular disease in some patient groups. Betaine supplementation lowers
      plasma total homocysteine. OBJECTIVE: We compared the acute effects of dietary
      and supplementary betaine and choline on plasma betaine and homocysteine under
      standard conditions and after a methionine load. DESIGN: In a randomized
      crossover study, 8 healthy men (19-40 y) consumed a betaine supplement
      (approximately 500 mg), high-betaine meal (approximately 517 mg), choline
      supplement (500 mg), high-choline meal (approximately 564 mg), high-betaine and 
      choline meal (approximately 517 mg betaine, approximately 622 mg choline), or a
      low-betaine and -choline control meal under standard conditions or postmethionine
      load. Plasma betaine, dimethylglycine, and homocysteine concentrations were
      measured hourly for 8 h and at 24 h after treatment. RESULTS: Dietary and
      supplementary betaine raised plasma betaine concentrations relative to control (P
      < 0.001) under standard conditions. This was not associated with raised plasma
      dimethylglycine concentration, and no significant betaine appeared in the urine.
      A small increase in dimethylglycine excretion was observed when either betaine or
      choline was supplied (P = 0.011 and < 0.001). Small decreases in plasma
      homocysteine 6 h after ingestion under standard conditions (P < or = 0.05) were
      detected after a high-betaine meal and after a high-betaine and high-choline
      meal. Dietary betaine and choline and betaine supplementation attenuated the
      increase in plasma homocysteine at both 4 and 6 h after a methionine load (P < or
      = 0.001). CONCLUSIONS: Dietary betaine and supplementary betaine acutely increase
      plasma betaine, and they and choline attenuate the postmethionine load rise in
      homocysteine concentrations.

PMID- 18326595
TI  - Associations between physical activity, body fat, and insulin resistance
      (homeostasis model assessment) in adolescents: the European Youth Heart Study.
AB  - BACKGROUND: More and better data are needed to understand the action of physical
      activity (PA) on insulin resistance and the concomitant relation with body fat in
      adolescence. OBJECTIVE: We examined the relation between total PA and intensity
      levels with insulin resistance under special consideration of waist circumference
      and skinfold thickness. DESIGN: This was a cross-sectional study of 613
      adolescents (352 girls, 261 boys) with a mean (+/-SD) age of 15.5 +/- 0.5 y from
      Sweden and Estonia. Total, low, moderate, and vigorous PA was measured by
      accelerometry. Body fat estimators included waist circumference and the sum of 5
      skinfold thicknesses. Fasting insulin and glucose were measured, and insulin
      resistance was calculated according to the homeostasis model assessment (HOMA).
      Linear regression analysis and analysis of covariance were used to determine the
      association between PA and insulin resistance while considering body fat. All
      estimates were adjusted for sex, country, pubertal status, and indicators of body
      fat when applicable. RESULTS: Total, moderate, and vigorous PA were inversely
      correlated with HOMA. Body fat estimators were positively correlated with HOMA.
      Significant contrasts in HOMA concentrations were seen when comparing the lower 2
      tertiles with the upper tertile of PA indicators. Repeating the analysis with
      body fat estimators showed significant contrasts in HOMA concentrations when
      comparing the lower tertiles with the upper tertile. CONCLUSION: In view of an
      increase in obesity in young people, the results accentuate the role of PA in
      sustaining metabolic balance in adolescence and the potential benefit of an
      increase of time spent at higher PA levels for youth with relatively elevated
      amounts of body fat.

PMID- 18326596
TI  - Study of the effect of trans fatty acids from ruminants on blood lipids and other
      risk factors for cardiovascular disease.
AB  - BACKGROUND: The intake of trans fatty acids (TFA) from industrially hydrogenated
      vegetable oils (iTFA) is known to have a deleterious effect on cardiovascular
      health, the effects of TFA from ruminants (rTFA) are virtually unknown.
      OBJECTIVE: The purpose of the present study was to compare the effects of rTFA
      and iTFA on plasma LDL concentrations and other cardiovascular disease risk
      factors in healthy subjects. DESIGN: In a double-blind, randomized crossover
      controlled study, 38 healthy men were fed each of 4 experimental isoenergetic
      diets lasting 4 wk each. The 4 diets were high in rTFA (10.2 g/2500 kcal),
      moderate in rTFA (4.2 g/2500 kcal), high in iTFA (10.2 g/2500 kcal), and low in
      TFA from any source (2.2 g/2500 kcal) (control diet). RESULTS: Plasma LDL
      cholesterol concentrations were significantly higher after the high- rTFA diet
      than after the control (P = 0.03) or the moderate- rTFA (P = 0.002) diet. Plasma
      LDL-cholesterol concentrations also were significantly (P = 0.02) higher after
      the iTFA diet than after the moderate-rTFA diet. Plasma HDL-cholesterol
      concentrations were significantly (P = 0.02) lower after the high-rTFA diet than
      after the moderate-rTFA diet. Finally, all risk factors were comparable between
      the control and the moderate-rTFA diets. CONCLUSIONS: These results suggest that,
      whereas a high dietary intake of TFA from ruminants may adversely affect
      cholesterol homeostasis, moderate intakes of rTFA that are well above the upper
      limit of current human consumption have neutral effects on plasma lipids and
      other cardiovascular disease risk factors.

PMID- 18326597
TI  - Visceral adipose tissue and the ratio of visceral to subcutaneous adipose tissue
      are greater in adults with than in those without spinal cord injury, despite
      matching waist circumferences.
AB  - BACKGROUND: Abdominal obesity, particularly visceral adipose tissue (VAT), is
      associated with an increased risk of coronary heart disease (CHD). Despite an
      elevated risk of CHD mortality in persons with spinal cord injury (SCI), neither
      abdominal adipose tissue accumulation nor the validity of waist circumference
      (WC) has been determined in persons with SCI. OBJECTIVES: The objectives of this
      study were to compare total adipose tissue (TAT), visceral adipose tissue (VAT),
      subcutaneous adipose tissue (SAT), and the ratio of VAT to SAT (VAT:SAT) between
      adults with SCI and age-, sex-, and WC-matched able-bodied (AB) controls and to
      determine the relation between WC and VAT in both groups. DESIGN: Thirty-one men
      and women (n = 15 SCI and 16 AB) with a mean (+/-SD) age of 38.9 +/- 7.9 y
      participated in this cross-sectional study. Abdominal adipose tissue was
      quantified by computed tomography at L4-L5. WC was measured at 3 sites: lowest
      rib, iliac crest, and the midpoint between the lowest rib and iliac crest.
      RESULTS: Persons with SCI had a 58% greater mean VAT (P = 0.003), 48% greater
      mean VAT:SAT (P = 0.034), and 26% greater mean TAT (P = 0.055) than did matched
      AB controls after differences in weight were accounted for. Mean SAT was not
      significantly different between groups. WC at all sites was correlated with VAT
      in both groups (SCI: 0.905 < or = r < or = 0.925; AB: 0.838 < or = r < or =
      0.877; both P < 0.001). CONCLUSIONS: High levels of VAT exist in young people
      with SCI who classify themselves as active and healthy. WC may be a valid
      surrogate measure of VAT in this population and serve as a tool for clinicians to
      identify those at risk of CHD.

PMID- 18326598
TI  - Vitamin D insufficiency in southern Arizona.
AB  - BACKGROUND: Vitamin D deficiency or insufficiency has been observed among
      populations in the northern United States. However, data on the prevalence of
      vitamin D deficiency in areas of high sun exposure, such as Arizona, are limited.
      OBJECTIVE: The purpose of this study was to analyze serum 25-hydroxyvitamin D
      [25(OH)D] concentrations in residents of southern Arizona and to evaluate
      predictors of 25(OH)D in this population. DESIGN: Cross-sectional analyses of
      serum from participants in a colorectal adenoma prevention study were conducted
      to determine rates of vitamin D deficiency. Participants were categorized into 4
      groups on the basis of serum 25(OH)D concentrations: <10.0 ng/mL, > or =10.0
      ng/mL and <20.0 ng/mL, > or =20.0 ng/mL and <30.0 ng/mL, and > or =30.0 ng/mL.
      RESULTS: The mean serum 25(OH)D concentration for the total population was 26.1
      +/- 9.1 ng/mL. Of 637 participants, 22.3% had 25(OH)D concentrations >30 ng/mL,
      25.4% had concentrations <20 ng/mL, and 2.0% had concentrations <10 ng/mL. Blacks
      (55.5%) and Hispanics (37.6%) were more likely to have deficient 25(OH)D
      concentrations (<20 ng/mL) than were non-Hispanic whites (22.7%). Sun exposure
      had a greater effect on 25(OH)D in whites than in blacks and Hispanics, whereas
      BMI appeared to be more important in the latter groups. CONCLUSION: Despite
      residing in a region with high chronic sun exposure, adults in southern Arizona
      are commonly deficient in vitamin D deficiency, particularly blacks and
      Hispanics.

PMID- 18326599
TI  - The use of multiple logistic regression to identify risk factors associated with
      anemia and iron deficiency in a convenience sample of 12-36-mo-old children from
      low-income families.
AB  - BACKGROUND: The prevalence of iron deficiency (ID) anemia among preschool-age
      children remains relatively high in some areas across the United States.
      Determination of risk factors associated with ID is needed to allow children with
      identifiable risk factors to receive appropriate education, testing, and follow
      up. OBJECTIVE: We aimed to evaluate risk factors associated with anemia and ID in
      a sample of children participating in or applying for the Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC). DESIGN: The study was a
      cross-sectional study of a convenience sample of 12-36-mo-old children recruited
      from WIC clinics in 2 California counties (n = 498). RESULTS: Current WIC
      participation by the child and a greater rate of weight gain were negatively
      associated, and current maternal pregnancy was positively associated with anemia
      (hemoglobin < 110 g/L at 12-<24 mo or < 111 g/L at 24-36 mo) after control for
      age, sex, and ethnicity. Maternal WIC participation during pregnancy, child age,
      and the intake of > or =125 mL orange or tomato juice/d were negatively
      associated, and being male and living in an urban location were positively
      associated with ID (> or =2 of the following abnormal values: ferritin < or = 8.7
      microg/L, transferrin receptors > or = 8.4 microg/mL, and transferrin saturation
      < or = 13.2%). CONCLUSIONS: Current WIC participation by the child and maternal
      WIC participation during pregnancy were negatively associated with anemia and ID,
      respectively. It is anticipated that the risk factors identified in this study
      will be included in the development of an educational intervention focused on
      reducing the risk factors for ID and ID anemia in young children.

PMID- 18326600
TI  - Weight-loss diet that includes consumption of medium-chain triacylglycerol oil
      leads to a greater rate of weight and fat mass loss than does olive oil.
AB  - BACKGROUND: Clinical studies have shown that consumption of medium-chain
      triacylglycerols (MCTs) leads to greater energy expenditure than does consumption
      of long-chain triacylglycerols. Such studies suggest that MCT consumption may be
      useful for weight management. OBJECTIVE: We aimed to determine whether
      consumption of MCT oil improves body weight and fat loss compared with olive oil
      when consumed as part of a weight-loss program. DESIGN: Forty-nine overweight men
      and women, aged 19-50 y, consumed either 18-24 g/d of MCT oil or olive oil as
      part of a weight-loss program for 16 wk. Subjects received weekly group weight
      loss counseling. Body weight and waist circumference were measured weekly.
      Adipose tissue distribution was assessed at baseline and at the endpoint by use
      of dual-energy X-ray absorptiometry and computed tomography. RESULTS: Thirty-one
      subjects completed the study (body mass index: 29.8 +/- 0.4, in kg/m(2)). MCT oil
      consumption resulted in lower endpoint body weight than did olive oil (-1.67 +/-
      0.67 kg, unadjusted P = 0.013). There was a trend toward greater loss of fat mass
      (P = 0.071) and trunk fat mass (P = 0.10) with MCT consumption than with olive
      oil. Endpoint trunk fat mass, total fat mass, and intraabdominal adipose tissue
      were all lower with MCT consumption than with olive oil consumption (all
      unadjusted P values < 0.05). CONCLUSIONS: Consumption of MCT oil as part of a
      weight-loss plan improves weight loss compared with olive oil and can thus be
      successfully included in a weight-loss diet. Small changes in the quality of fat
      intake can therefore be useful to enhance weight loss.

PMID- 18326602
TI  - Effect of carbohydrate distribution on postprandial glucose peaks with the use of
      continuous glucose monitoring in type 2 diabetes.
AB  - BACKGROUND: Large postprandial glucose peaks are associated with increased risk
      of diabetic complications and cardiovascular disease. OBJECTIVE: We investigated
      the effect of carbohydrate distribution on postprandial glucose peaks with
      continuous blood glucose monitoring (CGMS), when consuming a moderate
      carbohydrate diet in energy balance in subjects with type 2 diabetes. DESIGN:
      Twenty-three subjects with type 2 diabetes were randomly assigned to each of four
      3-d interventions in a crossover design with a 4-d washout period. Identical
      foods were provided for each treatment with a ratio of total carbohydrate to
      protein to fat of 40%:34%:26% but differing in carbohydrate content at each meal:
      even distribution (CARB-E; approximately 70 g carbohydrate), breakfast (CARB-B),
      lunch (CARB-L), and dinner(CARB-D), each providing approximately 125 g
      carbohydrate in the loaded meal in a 9-MJ diet. Glucose concentrations were
      continuously measured with CGMS. Outcomes were assessed by postprandial peak
      glucose (G(max)), time spent > 12 mmol/L (T > 12), and total area under the
      glucose curve (AUC(20)). RESULTS: Daily G(max) differed between treatments (P =
      0.003) with CARB-L (14.2 +/- 1.0 mmol/L), CARB-E (14.5 +/- 0.9 mmol/L), and CARB
      D (14.6 +/- 0.8 mmol/L) being similar but lower than CARB-B (16.5 +/- 0.8
      mmol/L). Meal G(max) was weakly related to carbohydrate amount and glycemic load
      (r = 0.40-0.44). T > 12 differed between treatments (P = 0.014), and a treatment
      x fasting blood glucose (FBG) interaction (P = 0.003) was observed with CARB-L
      (184 +/- 74 min) < CARB-B (190 +/- 49 min) < CARB-D (234 +/- 87 min) < CARB-E
      (262 +/- 91 min). Total AUC(20) was not significantly different between
      treatments. After adjustment for FBG, treatment became significant (P = 0.006);
      CARB-L (10 049 +/- 718 mmol/L x 20 h) < CARB-E (10 493 +/- 706 mmol/L x 20 h) <
      CARB-B (10 603 +/- 642 mmol/L x 20 h) < CARB-D (10 717 +/- 638 mmol/L x 20 h).
      CONCLUSION: CARB-E did not optimize blood glucose control as assessed by
      postprandial peaks, whereas CARB-L provided the most favorable postprandial
      profile.

PMID- 18326601
TI  - Glycemic index, glycemic load, and chronic disease risk--a meta-analysis of
      observational studies.
AB  - BACKGROUND: Inconsistent findings from observational studies have prolonged the
      controversy over the effects of dietary glycemic index (GI) and glycemic load
      (GL) on the risk of certain chronic diseases. OBJECTIVE: The objective was to
      evaluate the association between GI, GL, and chronic disease risk with the use of
      meta-analysis techniques. DESIGN: A systematic review of published reports
      identified a total of 37 prospective cohort studies of GI and GL and chronic
      disease risk. Studies were stratified further according to the validity of the
      tools used to assess dietary intake. Rate ratios (RRs) were estimated in a Cox
      proportional hazards model and combined by using a random-effects model. RESULTS:
      From 4 to 20 y of follow-up across studies, a total of 40 129 incident cases were
      identified. For the comparison between the highest and lowest quantiles of GI and
      GL, significant positive associations were found in fully adjusted models of
      validated studies for type 2 diabetes (GI RR = 1.40, 95% CI: 1.23, 1.59; GL RR =
      1.27, 95% CI: 1.12, 1.45), coronary heart disease (GI RR = 1.25, 95% CI: 1.00,
      1.56), gallbladder disease (GI RR = 1.26, 95% CI: 1.13, 1.40; GL RR = 1.41, 95%
      CI: 1.25, 1.60), breast cancer (GI RR = 1.08, 95% CI: 1.02, 1.16), and all
      diseases combined (GI RR = 1.14, 95% CI: 1.09, 1.19; GL RR = 1.09, 95% CI: 1.04,
      1.15). CONCLUSIONS: Low-GI and/or low-GL diets are independently associated with
      a reduced risk of certain chronic diseases. In diabetes and heart disease, the
      protection is comparable with that seen for whole grain and high fiber intakes.
      The findings support the hypothesis that higher postprandial glycemia is a
      universal mechanism for disease progression.

PMID- 18326603
TI  - Effect of cereal test breakfasts differing in glycemic index and content of
      indigestible carbohydrates on daylong glucose tolerance in healthy subjects.
AB  - BACKGROUND: Frequent hyperglycemic episodes are increasingly being associated
      with an increased risk of type 2 diabetes and cardiovascular disease. OBJECTIVE:
      We studied the extent to which acute glycemia and glycemia after subsequent meals
      can be modulated by the characteristics of cereal foods, such as glycemic index
      (GI) and content of indigestible carbohydrates. DESIGN: Twelve healthy subjects
      consumed test meals in a random order. In series 1, the test meals were consumed
      at breakfast, and postprandial blood glucose incremental areas under the curve
      (IAUCs) were calculated after the test breakfast, standardized lunch, and
      standardized dinner. In series 2, the subjects consumed test evening meals and
      IAUCs were calculated after a subsequent standardized breakfast. Breath hydrogen
      was measured as an indicator of colonic fermentation. RESULTS: Barley or rye
      kernel breakfasts lowered the blood glucose IAUC (0-120 min) at breakfast, at a
      subsequent lunch, and the cumulative IAUCs (breakfast+lunch+dinner) when compared
      with white-wheat bread (P < 0.05). The lunch blood glucose IAUCs were positively
      correlated with breakfast IAUCs (r = 0.30, P < 0.05). Breath hydrogen excretion
      was negatively correlated with blood glucose IAUCs after lunch (r = -0.33, P <
      0.05) and dinner (r = -0.22, P < 0.05). A barley kernel evening meal resulted in
      lower IAUCs (P < 0.05) and higher breath hydrogen (P < 0.001) after a subsequent
      breakfast compared with white-wheat bread. CONCLUSIONS: Glucose tolerance at
      subsequent meals can be notably improved during the course of a whole day or
      overnight by choosing specific low-GI, whole-grain cereal products. A low GI may
      be sufficient to achieve a second-meal effect from breakfast to lunch. A specific
      indigestible carbohydrate mixture appears to be required to show benefits on
      glucose tolerance in a longer time frame (9.5 h), most likely mediated through
      colonic fermentation.

PMID- 18326604
TI  - Glycemic index and glycemic load in relation to food and nutrient intake and
      metabolic risk factors in a Dutch population.
AB  - BACKGROUND: Previous studies on the glycemic index (GI) and glycemic load (GL)
      reported inconsistent findings on their association with metabolic risk factors.
      This may partly have been due to differences in underlying dietary patterns.
      OBJECTIVE: We aimed to examine the association of GI and GL with food and
      nutrient intake and with metabolic risk factors including blood glucose, insulin,
      lipids, and high-sensitivity C-reactive protein (CRP). DESIGN: The study entailed
      cross-sectional analyses of data from 2 joint observational studies, the CoDAM
      Study and the Hoorn Study. RESULTS: In total, 974 subjects aged 42-87 y were
      included in the study. The mean (+/-SD) GI was 57 +/- 4 and the mean GL was 130
      +/- 39. Dairy products, potatoes and other tubers, cereal products, and fruit
      were the main predictive food groups for GI. GL was closely correlated with
      intake of total carbohydrates (r(s) = 0.97), which explained >95% of the
      variation in GL. After adjustment for potential confounders, GI was significantly
      inversely associated with HDL cholesterol and positively associated with fasting
      insulin, the homeostasis model assessment index of insulin resistance, the ratio
      of total to HDL cholesterol, and CRP. No association was observed between GL and
      any of the metabolic risk factors, except for a borderline significant positive
      association with CRP. CONCLUSIONS: In this population, a low-GI diet, which is
      high in dairy and fruit but low in potatoes and cereals, is associated with
      improved insulin sensitivity and lipid metabolism and reduced chronic
      inflammation. GL is highly correlated with carbohydrate intake and is not clearly
      associated with the investigated metabolic risk factors.

PMID- 18326605
TI  - Alkaline diets favor lean tissue mass in older adults.
AB  - BACKGROUND: Maintaining muscle mass while aging is important to prevent falls and
      fractures. Metabolic acidosis promotes muscle wasting, and the net acid load from
      diets that are rich in net acid-producing protein and cereal grains relative to
      their content of net alkali-producing fruit and vegetables may therefore
      contribute to a reduction in lean tissue mass in older adults. OBJECTIVE: We
      aimed to determine whether there was an association of 24-h urinary potassium and
      an index of fruit and vegetable content of the diet with the percentage lean body
      mass (%LBM) or change in %LBM in older subjects. DESIGN: Subjects were 384 men
      and women > or =65 y old who participated in a 3-y trial comparing calcium and
      vitamin D with placebo. Potassium was measured in 24-h urine collections at
      baseline. The %LBM, defined as total body nonfat, nonbone tissue weight/weight x
      100, was measured by using dual-energy X-ray absorptiometry at baseline and at 3
      y. Physical activity, height, and weight were assessed at baseline and at 3 y.
      RESULTS: At baseline, the mean urinary potassium excretion was 67.0 +/- 21.1
      mmol/d. Urinary potassium (mmol/d) was significantly positively associated with
      %LBM at baseline (beta = 0.033, P = 0.006; adjusted for sex, weight, and nitrogen
      excretion) but not with 3-y change in %LBM. Over the 3-y study, %LBM increased by
      2.6 +/- 3.6%. CONCLUSION: Higher intake of foods rich in potassium, such as fruit
      and vegetables, may favor the preservation of muscle mass in older men and women.

PMID- 18326606
TI  - Increasing habitual protein intake results in reduced postprandial efficiency of
      peripheral, anabolic wheat protein nitrogen use in humans.
AB  - BACKGROUND: The postprandial retention of dietary protein decreases when the
      prevailing protein intake increases. OBJECTIVE: We investigated the influence of
      the prevailing protein intake on the regional utilization and anabolic use of
      wheat protein during the postprandial non-steady state in humans. DESIGN: Healthy
      adults (n = 8) were adapted for 7 d, first to a normal-protein diet (NP: 1 g x
      kg(-1) x d(-1)) and then to a high-protein diet (HP: 2 g x kg(-1) x d(-1)). After
      each adaptation period, the subjects received the same single, solid mixed meal
      containing [15N]-labeled wheat protein. The postprandial kinetics of dietary
      nitrogen were then measured for 8 h in blood and urine. These data were further
      analyzed by using a multicompartmental model to predict the postprandial kinetics
      of dietary nitrogen in unsampled pools. RESULTS: The postprandial whole-body
      retention of wheat protein nitrogen, measured 8 h after meal ingestion, decreased
      by 10% when the subjects switched from the NP diet to the HP diet. According to
      modeling results, this resulted from an increased splanchnic utilization of
      dietary nitrogen for urea production, whereas its incorporation into splanchnic
      proteins was unchanged, leading to a 20-30% decrease in peripheral availability
      and anabolic use in HP-adapted compared with NP-adapted subjects having ingested
      the same protein load. CONCLUSIONS: By combining clinical experimentation with
      compartmental modeling, we provide a global overview of postprandial dietary
      protein metabolism. Increasing prior protein intake was shown to reduce the
      postprandial retention of wheat protein nitrogen, mainly by diminishing the
      efficiency of its peripheral availability and anabolic use.

PMID- 18326607
TI  - Demographic, anthropometric, and lifestyle factors and dietary intakes in
      relation to daidzein-metabolizing phenotypes among premenopausal women in the
      United States.
AB  - BACKGROUND: The soy isoflavone daidzein is metabolized to equol and O
      desmethylangolensin (ODMA) by intestinal bacteria in approximately 30-50% and 80
      90% of persons, respectively. Studies suggest beneficial health effects
      associated with daidzein-metabolizing phenotypes; thus, assessing their
      determinants is an important goal. OBJECTIVE: We evaluated relations between
      daidzein-metabolizing phenotypes and demographic, anthropometric, lifestyle, and
      dietary factors among premenopausal women in the United States. DESIGN: Two
      hundred women provided a first-void urine sample after a 3-d soy challenge and
      completed a health and demographics questionnaire, physical activity
      questionnaire, food-frequency questionnaire, and 3-d food record. Urine samples
      were measured for isoflavones by gas chromatography-mass spectrometry to
      determine daidzein-metabolizing phenotypes. RESULTS: Fifty-five (27.5%) and 182
      (91%) women had detectable concentrations of urinary equol and ODMA (>87.5
      ng/mL), respectively, and were classed as producers of these metabolites.
      Compared with nonproducers, equol producers were more likely (P < or = 0.05) to
      be Hispanic or Latino, to be highly educated, and to have frequent constipation,
      and ODMA producers were taller and less likely to be Asian than white. Equol and
      ODMA producers reported higher overall physical activity than did nonproducers.
      CONCLUSIONS: We observed associations between equol production and ethnicity,
      education, constipation, and physical activity and between ODMA production and
      race, height, and physical activity. Associations with race and ethnicity were
      based on small numbers of Asian and Hispanic or Latino women, and confirmation of
      these findings is needed. Few dietary factors, assessed with the use of either a
      food-frequency questionnaire or food record, were associated with daidzein
      metabolizing phenotypes.

PMID- 18326608
TI  - Pharmacokinetics of a single, large dose of cholecalciferol.
AB  - BACKGROUND: There is much interest in dosing vitamin D intermittently for patient
      convenience and long-term adherence. OBJECTIVE: The objective was to characterize
      the time course and response of 25-hydroxyvitamin D (calcidiol) to a large oral
      dose of cholecalciferol. DESIGN: One group (30 subjects) was supplemented with a
      single oral dose of 100,000 IU cholecalciferol. A second group (10 subjects)
      served as a control group to assess the seasonal change of calcidiol. Serum
      calcidiol concentrations were followed for 4 mo. The subjects were healthy with
      limited sun exposure (<10 h/wk) and milk consumption (<0.47 L daily). We excluded
      subjects with granulomatous conditions, liver disease, kidney disease, or
      diabetes and subjects taking anticonvulsants, barbiturates, or steroids. RESULTS:
      Serum calcidiol rose promptly after cholecalciferol dosing from a mean (+/-SD)
      baseline of 27.1 +/- 7.7 ng/mL to a concentration maximum of 42.0 +/- 9.1 ng/mL.
      Seven percent of the supplemented cohort failed to achieve 32.1 ng/mL at any time
      point. The highest achieved concentration in any subject was 64.2 ng/mL. The
      control group had a nonsignificant change from baseline of -0.72 +/- 0.80 ng/mL
      during 4 mo. CONCLUSIONS: Cholecalciferol (100,000 IU) is a safe, effective, and
      simple way to increase calcidiol concentrations. The dosing interval should be <
      or =2 mo to ensure continuous serum calcidiol concentrations above baseline. This
      trial was registered at www.clinicaltrials.gov as #NCT00473239.

PMID- 18326609
TI  - Dynamic coordination of macronutrient balance during infant growth: insights from
      a mathematical model.
AB  - BACKGROUND: Complex dynamic changes in body composition, dietary intake, energy
      expenditure, and macronutrient oxidation occur during infant growth. Although
      previous investigators have focused on energy requirements for normal growth,
      little is known about the dynamic coordination of macronutrient balance.
      OBJECTIVE: Our objective was to develop a mathematical model of the dynamic
      relations between diet, macronutrient oxidation, and energy expenditure during
      normal infant growth. DESIGN: We developed a mathematical model that integrates
      longitudinal data on changes of body composition and carbon dioxide production
      determined with the doubly labeled water method to calculate both energy intake
      requirements and macronutrient oxidation rates during normal infant growth.
      RESULTS: The calculated fat oxidation rate was initially <20 kcal x kg(-1) x d(
      1), despite the consumption of >60 kcal x kg(-1) x d(-1) of dietary fat. This
      discrepancy was maintained until approximately 6 mo, after which fat intake was
      only slightly greater than fat oxidation. Nonfat oxidation closely followed
      nonfat dietary intake for the duration of the period studied. Model calculations
      of the energy intake requirements for normal growth were slightly lower than
      previous estimates. The calculations were robust to variations of body weight,
      body composition, and diet composition input data, but depended sensitively on
      variations of carbon dioxide production data. CONCLUSIONS: Our model presents a
      dynamic picture of how macronutrient oxidation adapts in concert with dietary
      changes and energy expenditure to give rise to normal tissue deposition. The
      model integrates a variety of data in a self-consistent way, simulating the
      complex metabolic adaptations occurring during normal growth while extracting
      important physiologic information from the data that would otherwise be
      unavailable.

PMID- 18326610
TI  - Effects of prenatal food and micronutrient supplementation on infant development:
      a randomized trial from the Maternal and Infant Nutrition Interventions, Matlab
      (MINIMat) study.
AB  - BACKGROUND: Few data exist for the effects of multiple micronutrient (MM) or food
      supplementation to undernourished pregnant women on their offsprings'
      development. OBJECTIVE: We aimed to compare the effects on infant development of
      early (8-10 wk gestation) or usual ( approximately 17 wk gestation)
      supplementation with food and MM, 30 mg Fe + 400 microg folate, or 60 mg Fe + 400
      microg folate. DESIGN: A large, randomized, controlled trial of pregnancy
      supplementation was conducted in Bangladesh. A subsample of infants (n = 2853)
      were assessed on 2 problem-solving tests (support and cover tests), the motor
      index of the Bayley Scales of Infant Development, and Wolke's behavior ratings at
      7 mo of age. RESULTS: There were no significant effects of any intervention in
      the group as a whole. However, infants of undernourished mothers [body mass index
      (BMI; in kg/m2) < 18.5] who received early food supplementation performed
      slightly but significantly (P = 0.035) better on the support test than did
      infants of mothers who received usual food supplementation (z score: 0.17; 95%
      CI: 0.01, 0.33). There were no benefits in infants of higher-BMI mothers (P =
      0.024 for BMI x food interaction). Children of low-BMI mothers who received MMs
      had slightly better motor scores (z score: 0.28; 95% CI: 0.08, 0.48) and activity
      ratings (z score: 0.24; 95% CI: 0.037, 0.45) than did those who received 30 mg Fe
      + 400 microg folate, whereas other children did not benefit (P = 0.05 for both
      motor scores and BMI x micronutrients and for activity and BMI x micronutrients).
      CONCLUSIONS: Small benefits from early food and MM supplementation were found in
      infants of low-BMI but not of high-BMI mothers. However, the benefits were of
      doubtful functional importance, and longer follow-up is required to determine
      programmatic implications.

PMID- 18326611
TI  - Diet and risk factors for age-related maculopathy.
AB  - BACKGROUND: Evidence continues to accumulate that oxidative stress is
      etiologically important in the pathogenesis of age-related maculopathy (ARM) and
      that appropriate antioxidants of dietary origin may protect against this
      condition. OBJECTIVE: Risk factors for ARM may be classed as established or
      putative. We report a study designed to investigate whether such risk factors are
      associated with a dietary lack of antioxidants relevant to retinal health.
      DESIGN: Dietary, anthropometric, and sociodemographic details relating to 828
      healthy Irish subjects aged 20-60 y were recorded in a cross-sectional fashion
      and analyzed for associations between risk factors for ARM and dietary intake of
      relevant nutrients. RESULTS: Of the established risk factors for ARM, increasing
      age was associated with a relative lack of dietary zeaxanthin (P < 0.05) and
      tobacco use with a relative lack of dietary vitamin C (P < 0.05). Of the putative
      risk factors for ARM, alcohol consumption was associated with a relative lack of
      dietary alpha-linoleic acid (P < 0.05), and female sex was associated with a
      relative lack of dietary zinc (P < 0.05). CONCLUSIONS: We showed that several
      variables related to risk for ARM are associated with a relative dietary lack of
      key nutrients. Our finding that age, the most important and universal risk factor
      for ARM, is associated with a relative lack of dietary zeaxanthin, is an
      important finding that warrants further investigation.

PMID- 18326612
TI  - Dose-response trial of prophylactic zinc supplements, with or without copper, in
      young Ecuadorian children at risk of zinc deficiency.
AB  - BACKGROUND: Multiple studies have shown the benefits of zinc supplementation
      among young children in high-risk populations. However, the optimal dose and safe
      upper level of zinc have not been determined. OBJECTIVES: The objectives of this
      study were to measure the effects of different doses of supplemental zinc on the
      plasma zinc concentration, morbidity, and growth of young children; to detect any
      adverse effects of 10 mg supplemental Zn on markers of copper or iron status; and
      to determine whether any adverse effects are alleviated by providing copper with
      zinc. DESIGN: This randomized, double-masked, community-based intervention trial
      was conducted in 631 Ecuadorian children who were 12-30 mo old at baseline and
      who had initial length-for-age z scores <-1.3. Children received 1 of 5 daily
      supplements for 6 mo: 3, 7, or 10 mg Zn as zinc sulfate, 10 mg Zn + 0.5 mg Cu as
      copper sulfate, or placebo. RESULTS: The change in plasma zinc concentration from
      baseline was positively related to the zinc dose (P < 0.001). Zinc
      supplementation, including doses as low as 3 mg/d, reduced the incidence of
      diarrhea by 21-42% (P < 0.01). There were no other significant group-wise
      differences. CONCLUSIONS: Zinc supplementation with a dose as low as 3 mg/d
      increased plasma zinc concentrations and reduced diarrhea incidence in the study
      population. There were no observed adverse effects of 10 mg Zn/d on indicators of
      copper or iron status. The current tolerable upper level of zinc recommended by
      the Institute of Medicine should be reassessed for young children.

PMID- 18326613
TI  - Plasma folate, vitamin B-6, vitamin B-12, and risk of breast cancer in women.
AB  - BACKGROUND: B vitamins such as folate, vitamin B-6, and vitamin B-12 are
      coenzymes that are important for DNA integrity and stability. Deficiency in these
      B vitamins may promote tumor carcinogenesis. OBJECTIVE: We prospectively
      evaluated plasma concentrations of folate, pyridoxal 5-phosphate (PLP; the
      principal active form of vitamin B-6), and vitamin B-12 in relation to breast
      cancer risk. DESIGN: We included 848 incident cases of invasive breast cancer
      identified as of 31 March 2004, and 848 individually matched control subjects
      from 28 345 women in the Women's Health Study aged > or =45 y who provided blood
      samples and had no history of cancer and cardiovascular disease at baseline in
      1993. Logistic regression controlling for matching factors and other risk factors
      for breast cancer was used to estimate relative risks (RRs) and 95% CIs. All
      statistical tests were 2 sided. RESULTS: Plasma concentrations of folate, PLP,
      and vitamin B-12 were not associated with overall risk of breast cancer. Women in
      the highest quintile group relative to those in the lowest quintile had
      multivariate RRs of 1.42 (95% CI: 1.00, 2.02) for plasma folate (P for trend =
      0.21), 0.91 (95% CI: 0.63, 1.30) for plasma PLP (P for trend = 0.48), and 1.29
      (95% CI: 0.92, 1.82) for plasma vitamin B-12 (P for trend = 0.18). However,
      higher plasma folate concentrations were moderately associated with an increased
      risk of developing premenopausal breast cancer (P for trend = 0.04) and for
      developing estrogen receptor (ER)-positive or progesterone receptor (PR)-positive
      breast tumors (P for trend < or = 0.06). Conversely, an inverse association was
      seen between plasma PLP and postmenopausal breast cancer (P for trend = 0.04).
      CONCLUSIONS: Data from this study suggest that B vitamins, including folate,
      vitamin B-6, and vitamin B-12, may confer little or no reduction in overall risk
      of developing breast cancer. The observed positive associations of folate status
      with risk of developing premenopausal breast cancer and ER-positive or PR
      positive tumors are unexpected. Additional research is needed to elucidate the
      role of folate in breast cancer development.

PMID- 18326614
TI  - Postprandial triacylglycerol metabolism is modified by the presence of genetic
      variation at the perilipin (PLIN) locus in 2 white populations.
AB  - BACKGROUND: Several perilipin (PLIN) polymorphic sites have been studied for
      their potential use as markers for obesity and the metabolic syndrome. OBJECTIVE:
      We aimed to examine whether the presence of polymorphisms at the perilipin (PLIN)
      locus (PLIN1, 6209T-->C; PLIN4, 11482G-->A; PLIN5, 13041A-->G; and PLIN6, 14995A-
      >T) influence postprandial lipoprotein metabolism in 2 white populations. DESIGN:
      Eighty-eight healthy Spanish men and 271 healthy US subjects (men and women)
      underwent an oral-fat-load test in 2 independent studies. Blood samples were
      taken in the fasting state and during the postprandial phase at regular
      intervals. Total cholesterol and triacylglycerol and triacylglycerol in
      triacylglycerol-rich lipoproteins (TRL, large and small) were measured. RESULTS:
      Carriers of the minor C allele at the PLIN1 variant displayed lower postprandial
      concentrations of large-TRL triacylglycerol (Spanish subjects: P = 0.024; US
      subjects: P = 0.005) than did subjects carrying the T/T genotype. The same
      pattern was observed in the Spanish population at the PLIN4 locus (P = 0.015),
      and both SNPs were in strong linkage disequilibrium. In both populations,
      subjects carrying the minor C and A alleles at PLIN1 and PLIN4, respectively, had
      significantly lower postprandial concentrations of plasma triacylglycerol (P <
      0.05) and lower concentrations of small-TRL triacylglycerol than did those who
      were homozygous for the major alleles at PLIN1 and PLIN4 (Spanish subjects: P =
      0.020 and 0.008, respectively; US subjects: P = 0.021 and 0.035, respectively).
      CONCLUSION: These 2 studies suggest that the presence of the minor C and A
      alleles at PLIN1 and PLIN4, respectively, are associated with a lower
      postprandial response that may result in lower atherogenic risk for these
      persons.

PMID- 18326615
TI  - Cruciferous vegetables, the GSTP1 Ile105Val genetic polymorphism, and breast
      cancer risk.
AB  - BACKGROUND: Cruciferous vegetables are the primary source of isothiocyanates and
      other glucosinolate derivatives that are known to induce phase II detoxifying
      enzymes, including glutathione S-transferases (GSTs). OBJECTIVE: We investigated
      the independent and combined effects of cruciferous vegetable intake and the
      GSTP1 Ile(105)Val genetic polymorphism on breast cancer risk. DESIGN: Analyses
      included 3035 cases and 3037 population controls who were participating in the
      Shanghai Breast Cancer Study and for whom diet and genetic data were complete
      (87% of cases and 85% of controls). RESULTS: With the use of multivariate
      logistic regression, the GSTP1 Val/Val genotype was significantly associated with
      greater breast cancer risk (OR = 1.50; 95% CI: 1.12, 1.99). The association was
      significantly greater in premenopausal women (OR = 1.69; 95% CI: 1.17, 2.43) than
      in postmenopausal women (OR = 1.20; 95% CI: 0.74, 1.92). Total cruciferous
      vegetable intake was not significantly associated with breast cancer risk,
      although subjects reporting greater turnip (P for trend < 0.001) and Chinese
      cabbage (P for trend = 0.049) intakes had a significantly lower postmenopausal
      breast cancer risk. Women with the GSTP1 Val/Val genotype and low cruciferous
      vegetable intake had a breast cancer risk 1.74-fold (95% CI: 1.13, 2.67) that of
      women with the Ile/Ile or Ile/Val genotype. This effect of low cruciferous
      vegetable intake and the Val/Val genotype was seen predominantly among
      premenopausal women (OR = 2.08; 95% CI = 1.20, 3.59). CONCLUSIONS: Cruciferous
      vegetable intake consistent with high isothiocyanate exposure may reduce breast
      cancer risk. Cruciferous vegetable intake also may ameliorate the effects of the
      GSTP1 genotype.

PMID- 18326616
TI  - Long-term consumption of isoflavone-enriched foods does not affect bone mineral
      density, bone metabolism, or hormonal status in early postmenopausal women: a
      randomized, double-blind, placebo controlled study.
AB  - BACKGROUND: Osteoporosis is a major health problem. It was hypothesized that
      isoflavone-containing products may be a potential alternative to hormone
      replacement therapy for preventing bone loss during the menopausal transition.
      OBJECTIVE: The objective was to investigate whether the consumption of isoflavone
      enriched foods for 1 y affects bone mineral density, bone metabolism, and
      hormonal status in early postmenopausal women. DESIGN: This was a randomized,
      double-blind, placebo-controlled, parallel, multicenter trial. Two hundred thirty
      seven healthy early postmenopausal women [mean (+/-SD) age of 53 +/- 3 y and time
      since last menses of 33 +/- 15 mo] consumed isoflavone-enriched foods providing a
      mean daily intake of 110 mg isoflavone aglycones or control products for 1 y
      while continuing their habitual diet and lifestyle. Outcome measures included
      bone mineral density of the lumbar spine and total body, markers of bone
      formation and bone resorption, hormones, isoflavones in plasma and urine, safety
      variables, and adverse events. RESULTS: Consumption of isoflavone-enriched
      products did not alter bone mineral density of the lumbar spine and total body or
      markers of bone formation and bone resorption. Hormone concentrations did not
      differ between the isoflavone and control groups. Consumption of isoflavone
      enriched products resulted in increased isoflavone concentrations in plasma and
      urine, whereas control products did not. This finding indicated good compliance
      with treatment. Subgroup analysis did not support an effect of equol phenotype on
      bone density. The intervention had no effect on a range of safety variables and
      reported adverse events. CONCLUSION: Consumption of foods containing 110 mg/d of
      soy isoflavone aglycone equivalents for 1 y did not prevent postmenopausal bone
      loss and did not affect bone turnover in apparently healthy early postmenopausal
      white women. This trial was registered at clinicaltrials.gov as NCT00301353.

PMID- 18326617
TI  - The skeletal benefits of calcium- and vitamin D3-fortified milk are sustained in
      older men after withdrawal of supplementation: an 18-mo follow-up study.
AB  - BACKGROUND: In a previous 2-y randomized controlled trial, we showed that calcium
      and vitamin D3-fortified milk stopped or slowed bone loss at several clinically
      relevant skeletal sites in older men. OBJECTIVE: The present study aimed to
      determine whether the skeletal benefits of the fortified milk were sustained
      after withdrawal of the supplementation. DESIGN: One hundred nine men >50 y old
      who had completed a 2-y fortified milk trial were followed for an additional 18
      mo, during which no fortified milk was provided. Bone mineral density (BMD) of
      the total hip, femoral neck, lumbar spine, and forearm was measured by using dual
      energy X-ray absorptiometry. RESULTS: Comparison of the mean changes from
      baseline between the groups (adjusted for baseline age, BMD, total calcium
      intake, and change in weight) showed that the net beneficial effects of fortified
      milk on femoral neck and ultradistal radius BMD at the end of the intervention
      (1.8% and 1.5%, respectively; P < 0.01 for both) were sustained at 18-mo follow
      up (P < 0.05 for both). The nonsignificant between-group differences at the total
      hip (0.8%; P = 0.17) also persisted at follow-up (0.7%; P = 0.10), but there were
      no lasting benefits at the lumbar spine. The average total dietary calcium intake
      in the milk supplementation group at follow-up approximated recommended amounts
      for Australian men >50 y old (1000 mg/d) but did not differ significantly from
      that in the control subjects (1021 versus 890 mg/d). CONCLUSION: Supplementation
      with calcium- and vitamin D3-fortified milk for 2 y may provide some sustained
      benefits for BMD in older men after withdrawal of supplementation.

PMID- 18326618
TI  - Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy
      humans.
AB  - BACKGROUND: Green tea consumption is reportedly associated with various health
      promoting properties. For example, it has been shown to promote fat oxidation in
      humans at rest and to prevent obesity and improve insulin sensitivity in mice.
      OBJECTIVE: We investigated the effects of acute ingestion of green tea extract
      (GTE) on glucose tolerance and fat oxidation during moderate-intensity exercise
      in humans. DESIGN: Two studies were performed, both with a counter-balanced
      crossover design. In study A, 12 healthy men performed a 30-min cycling exercise
      at 60% of maximal oxygen consumption (VO2max) before and after supplementation.
      In study B, 11 healthy men took an oral-glucose-tolerance test before and after
      supplementation. In the 24-h period before the experimental trials, participants
      ingested 3 capsules containing either GTE (total: 890 +/- 13 mg polyphenols and
      366 +/- 5 mg EGCG) or a corn-flour placebo (total: 1729 +/- 22 mg). RESULTS:
      Average fat oxidation rates were 17% higher after ingestion of GTE than after
      ingestion of placebo (0.41 +/- 0.03 and 0.35 +/- 0.03 g/min, respectively; P <
      0.05). Moreover, the contribution of fat oxidation to total energy expenditure
      was also significantly higher, by a similar percentage, after GTE
      supplementation. The insulin area under the curve decreased in both the GTE and
      placebo trials (3612 +/- 301 and 4280 +/- 309 microIU/dL . 120 min, respectively;
      P < 0.01), and there was a concomitant increase of 13% in insulin sensitivity.
      CONCLUSIONS: Acute GTE ingestion can increase fat oxidation during moderate
      intensity exercise and can improve insulin sensitivity and glucose tolerance in
      healthy young men.

PMID- 18326619
TI  - Prebiotic evaluation of a novel galactooligosaccharide mixture produced by the
      enzymatic activity of Bifidobacterium bifidum NCIMB 41171, in healthy humans: a
      randomized, double-blind, crossover, placebo-controlled intervention study.
AB  - BACKGROUND: Galactooligosaccharides are selectively fermented by the beneficial
      member of the colonic microflora contributing to the health of the host.
      OBJECTIVE: We assessed the prebiotic potential of a novel galactooligosaccharide
      produced through the action of beta-galactosidases, originating from a probiotic
      Bifidobacterium bifidum strain, against a galactooligosaccharide produced through
      the action of an industrial beta-galactosidase and a placebo. DESIGN: Fifty-nine
      healthy human volunteers participated in this study. Initially, the effect of the
      matrix on the prebiotic properties of a commercially available
      galactooligosaccharide (7 g/d) was assessed during 7-d treatment periods with a 7
      d washout period in between. During the second phase, 30 volunteers were assigned
      to a sequence of treatments (7 d) differing in the amount of the novel
      galactooligosaccharide (0, 3.6, or 7 g/d). Stools were recovered before and after
      each intervention, and bacteria numbers were determined by fluorescent in situ
      hybridization. RESULTS: Addition of the novel galactooligosaccharide mixture
      significantly increased the bifidobacterial population ratio compared with the
      placebo (P < 0.05), whereas 7 g/d of the novel galactooligosaccharide
      significantly increased the bifidobacterial ratio compared with the commercial
      galactooligosaccharide (P < 0.05). Moreover, a significant relation (P < 0.001)
      between the bifidobacteria proportion and the novel galactooligosaccharide dose
      (0, 3.6, and 7 g/d) was observed. This relation was similar to the effect of the
      novel galactooligosaccharide on the prebiotic index of each dose. CONCLUSIONS:
      This study showed that galactooligosaccharide mixtures produced with different
      beta-galactosidases show different prebiotic properties and that, by using
      enzymes originating from bifidobacterial species, an increase in the bifidogenic
      properties of the prebiotic product is achievable.

PMID- 18326620
TI  - Calcium supplementation and cancer incidence.

PMID- 18326621
TI  - Artifact in the control group undermines the conclusions of a vitamin D and
      cancer study.

PMID- 18326622
TI  - Organization of the core structure of the postsynaptic density.
AB  - Much is known about the composition and function of the postsynaptic density
      (PSD), but less is known about its molecular organization. We use EM tomography
      to delineate the organization of PSDs at glutamatergic synapses in rat
      hippocampal cultures. The core of the PSD is dominated by vertically oriented
      filaments, and ImmunoGold labeling shows that PSD-95 is a component of these
      filaments. Vertical filaments contact two types of transmembrane structures whose
      sizes and positions match those of glutamate receptors and intermesh with two
      types of horizontally oriented filaments lying 10-20 nm from the postsynaptic
      membrane. The longer horizontal filaments link adjacent NMDAR-type structures,
      whereas the smaller filaments link both NMDA- and AMPAR-type structures. The
      orthogonal, interlinked scaffold of filaments at the core of the PSD provides a
      structural basis for understanding dynamic aspects of postsynaptic function.

PMID- 18326623
TI  - Genome-wide association study provides evidence for a breast cancer risk locus at
      6q22.33.
AB  - We performed a three-phase genome-wide association study (GWAS) using cases and
      controls from a genetically isolated population, Ashkenazi Jews (AJ), to identify
      loci associated with breast cancer risk. In the first phase, we compared allele
      frequencies of 150,080 SNPs in 249 high-risk, BRCA1/2 mutation-negative AJ
      familial cases and 299 cancer-free AJ controls using chi(2) and the Cochran
      Armitage trend tests. In the second phase, we genotyped 343 SNPs from 123 regions
      most significantly associated from stage 1, including 4 SNPs from the FGFR2
      region, in 950 consecutive AJ breast cancer cases and 979 age-matched AJ
      controls. We replicated major associations in a third independent set of 243 AJ
      cases and 187 controls. We obtained a significant allele P value of association
      with AJ breast cancer in the FGFR2 region (P = 1.5 x 10(-5), odds ratio (OR)
      1.26, 95% confidence interval (CI) 1.13-1.40 at rs1078806 for all phases
      combined). In addition, we found a risk locus in a region of chromosome 6q22.33
      (P = 2.9 x 10(-8), OR 1.41, 95% CI 1.25-1.59 at rs2180341). Using several SNPs at
      each implicated locus, we were able to verify associations and impute haplotypes.
      The major haplotype at the 6q22.33 locus conferred protection from disease,
      whereas the minor haplotype conferred risk. Candidate genes in the 6q22.33 region
      include ECHDC1, which encodes a protein involved in mitochondrial fatty acid
      oxidation, and also RNF146, which encodes a ubiquitin protein ligase, both known
      pathways in breast cancer pathogenesis.

PMID- 18326624
TI  - The distribution of category and location information across object-selective
      regions in human visual cortex.
AB  - Since Ungerleider and Mishkin [Underleider LG, Mishkin M (1982) Two cortical
      visual systems. Analysis of Visual Behavior, eds Ingle MA, Goodale MI, Masfield
      RJW (MIT Press, Cambridge, MA), pp 549-586] proposed separate visual pathways for
      processing object shape and location, steady progress has been made in
      characterizing the organization of the two kinds of information in extrastriate
      visual cortex in humans. However, to date, there has been no broad-based survey
      of category and location information across all major functionally defined object
      selective regions. In this study, we used an fMRI region-of-interest (ROI)
      approach to identify eight regions characterized by their strong selectivity for
      particular object categories (faces, scenes, bodies, and objects). Participants
      viewed four types of stimuli (faces, scenes, bodies, and cars) appearing in each
      of three different spatial locations (above, below, or at fixation). Analyses
      based on the mean response and voxelwise patterns of response in each ROI reveal
      location information in almost all of the known object-selective regions.
      Furthermore, category and location information can be read out independently of
      one another such that most regions contain both position-invariant category
      information and category-invariant position information. Finally, we find
      substantially more location information in ROIs on the lateral than those on the
      ventral surface of the brain, even though these regions have equal amounts of
      category information. Although the presence of both location and category
      information in most object-selective regions argues against a strict physical
      separation of processing streams for object shape and location, the ability to
      extract position-invariant category information and category-invariant position
      information from the same neural population indicates that form and location
      information nonetheless remain functionally independent.

PMID- 18326625
TI  - Consistent blind protein structure generation from NMR chemical shift data.
AB  - Protein NMR chemical shifts are highly sensitive to local structure. A robust
      protocol is described that exploits this relation for de novo protein structure
      generation, using as input experimental parameters the (13)C(alpha), (13)C(beta),
      (13)C', (15)N, (1)H(alpha) and (1)H(N) NMR chemical shifts. These shifts are
      generally available at the early stage of the traditional NMR structure
      determination process, before the collection and analysis of structural
      restraints. The chemical shift based structure determination protocol uses an
      empirically optimized procedure to select protein fragments from the Protein Data
      Bank, in conjunction with the standard ROSETTA Monte Carlo assembly and
      relaxation methods. Evaluation of 16 proteins, varying in size from 56 to 129
      residues, yielded full-atom models that have 0.7-1.8 A root mean square
      deviations for the backbone atoms relative to the experimentally determined x-ray
      or NMR structures. The strategy also has been successfully applied in a blind
      manner to nine protein targets with molecular masses up to 15.4 kDa, whose
      conventional NMR structure determination was conducted in parallel by the
      Northeast Structural Genomics Consortium. This protocol potentially provides a
      new direction for high-throughput NMR structure determination.

PMID- 18326626
TI  - Contribution of positively charged flanking residues to the insertion of
      transmembrane helices into the endoplasmic reticulum.
AB  - Positively charged residues located near the cytoplasmic end of hydrophobic
      segments in membrane proteins promote membrane insertion and formation of
      transmembrane alpha-helices. A quantitative understanding of this effect has been
      lacking, however. Here, using an in vitro transcription-translation system to
      study the insertion of model hydrophobic segments into dog pancreatic rough
      microsomes, we show that a single Lys or Arg residue typically contributes
      approximately -0.5 kcal/mol to the apparent free energy of membrane insertion
      (DeltaG(app)) when placed near the cytoplasmic end of a hydrophobic segment and
      that stretches of 3-6 Lys residues can contribute significantly to DeltaG(app)
      from a distance of up to approximately 13 residues away.

PMID- 18326627
TI  - Splicing mediates the activity of four putative cellular internal ribosome entry
      sites.
AB  - A growing number of cellular mRNAs are thought to possess internal ribosome entry
      sites (IRESs), sequences that permit translation of a transcript independent of
      its 5' end and cap structure. Although dicistronic assays are the canonical
      method of testing sequences for IRES activity, they may produce false-positive
      results if unanticipated monocistronic RNAs arise from the dicistronic construct
      used. Using a dicistronic reporter system and a green fluorescent protein-tagged
      retrovirus to evaluate six previously reported cellular IRESs, we found that four
      contain 3' splice sites whose activity was required for apparent IRES function
      and which resulted in formation of monocistronic transcripts by splicing.
      Bioinformatic analysis revealed that the 3' splice sites identified in three of
      these putative IRESs are used in their native mRNAs and that the fourth is likely
      an artifactual sequence created during cDNA cloning. Our findings demonstrate a
      need for reexamination of other reported cellular IRESs by using careful RNA
      structural analysis to rule out splicing as the source of perceived IRES
      activity.

PMID- 18326628
TI  - Mass spectrometry identifies and quantifies 74 unique histone H4 isoforms in
      differentiating human embryonic stem cells.
AB  - Epigenetic regulation through chromatin is thought to play a critical role in the
      establishment and maintenance of pluripotency. Traditionally, antibody-based
      technologies were used to probe for specific posttranslational modifications
      (PTMs) present on histone tails, but these methods do not generally reveal the
      presence of multiple modifications on a single-histone tail (combinatorial
      codes). Here, we describe technology for the discovery and quantification of
      histone combinatorial codes that is based on chromatography and mass
      spectrometry. We applied this methodology to decipher 74 discrete combinatorial
      codes on the tail of histone H4 from human embryonic stem (ES) cells. Finally, we
      quantified the abundances of these codes as human ES cells undergo
      differentiation to reveal striking changes in methylation and acetylation
      patterns. For example, H4R3 methylation was observed only in the presence of
      H4K20 dimethylation; such context-specific patterning exemplifies the power of
      this technique.

PMID- 18326629
TI  - Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar
      hypoplasia and quadrupedal locomotion in humans.
AB  - Quadrupedal gait in humans, also known as Unertan syndrome, is a rare phenotype
      associated with dysarthric speech, mental retardation, and varying degrees of
      cerebrocerebellar hypoplasia. Four large consanguineous kindreds from Turkey
      manifest this phenotype. In two families (A and D), shared homozygosity among
      affected relatives mapped the trait to a 1.3-Mb region of chromosome 9p24. This
      genomic region includes the VLDLR gene, which encodes the very low-density
      lipoprotein receptor, a component of the reelin signaling pathway involved in
      neuroblast migration in the cerebral cortex and cerebellum. Sequence analysis of
      VLDLR revealed nonsense mutation R257X in family A and single-nucleotide deletion
      c2339delT in family D. Both these mutations are predicted to lead to truncated
      proteins lacking transmembrane and signaling domains. In two other families (B
      and C), the phenotype is not linked to chromosome 9p. Our data indicate that
      mutations in VLDLR impair cerebrocerebellar function, conferring in these
      families a dramatic influence on gait, and that hereditary disorders associated
      with quadrupedal gait in humans are genetically heterogeneous.

PMID- 18326630
TI  - Molecular mechanisms that control initiation and termination of physiological
      depolarization-evoked transmitter release.
AB  - Ca(2+) is essential for physiological depolarization-evoked synchronous
      neurotransmitter release. But, whether Ca(2+) influx or another factor controls
      release initiation is still under debate. The time course of ACh release is
      controlled by a presynaptic inhibitory G protein-coupled autoreceptor (GPCR),
      whose agonist-binding affinity is voltage-sensitive. However, the relevance of
      this property for release control is not known. To resolve this question, we used
      pertussis toxin (PTX), which uncouples GPCR from its G(i/o) and in turn reduces
      the affinity of GPCR toward its agonist. We show that PTX enhances ACh and
      glutamate release (in mice and crayfish, respectively) and, most importantly,
      alters the time course of release without affecting Ca(2+) currents. These
      effects are not mediated by G(beta)gamma because its microinjection into the
      presynaptic terminal did not alter the time course of release. Also, PTX reduces
      the association of the GPCR with the exocytotic machinery, and this association
      is restored by the addition of agonist. We offer the following mechanism for
      control of initiation and termination of physiological depolarization-evoked
      transmitter release. At rest, release is under tonic block achieved by the
      transmitter-bound high-affinity presynaptic GPCR interacting with the exocytotic
      machinery. Upon depolarization, the GPCR uncouples from its G protein and
      consequently shifts to a low-affinity state toward the transmitter. The
      transmitter dissociates, the unbound GPCR detaches from the exocytotic machinery,
      and the tonic block is alleviated. The free machinery, together with Ca(2+) that
      had already entered, initiates release. Release terminates when the reverse
      occurs upon repolarization.

PMID- 18326631
TI  - Network properties of genes harboring inherited disease mutations.
AB  - By analyzing, in parallel, large literature-derived and high-throughput
      experimental datasets we investigate genes harboring human inherited disease
      mutations in the context of molecular interaction networks. Our results
      demonstrate that network properties influence the likelihood and phenotypic
      consequences of disease mutations. Genes with intermediate connectivities have
      the highest probability of harboring germ-line disease mutations, suggesting that
      disease genes tend to occupy an intermediate niche in terms of their
      physiological and cellular importance. Our analysis of tissue expression profiles
      supports this view. We show that disease mutations are less likely to occur in
      essential genes compared with all human genes. Disease genes display significant
      functional clustering in the analyzed molecular network. For about one-third of
      known disorders with two or more associated genes we find physical clusters of
      genes with the same phenotype. These clusters are likely to represent disorder
      specific functional modules and suggest a framework for identifying yet
      undiscovered disease genes.

PMID- 18326632
TI  - Attractive forces between cation condensed DNA double helices.
AB  - By combining single-molecule magnetic tweezers and osmotic stress on DNA
      assemblies, we separate attractive and repulsive components of the total
      intermolecular interaction between multivalent cation condensed DNA. Based on
      measurements of several different cations, we identify two invariant properties
      of multivalent cation-mediated DNA interactions: repulsive forces decay
      exponentially with a 2.3 +/- 0.1 A characteristic decay length and the attractive
      component of the free energy is always 2.3 +/- 0.2 times larger than the
      repulsive component of the free energy at force-balance equilibrium. These
      empirical constraints are not consistent with current theories that attribute DNA
      DNA attractions to a correlated lattice of counterions. The empirical constraints
      are consistent with theories for Debye-Huckel interactions between helical line
      charges and with the order-parameter formalism for hydration forces. Each of
      these theories posits exponentially decaying attractions and, if we assume this
      form, our measurements indicate a cation-independent, 4.8 +/- 0.5 A
      characteristic decay length for intermolecular attractions between condensed DNA
      molecules.

PMID- 18326633
TI  - Backbone dynamics of the 18.5 kDa isoform of myelin basic protein reveals
      transient alpha-helices and a calmodulin-binding site.
AB  - The 18.5 kDa isoform of myelin basic protein (MBP) is the predominant form in
      adult human central nervous system myelin. It is an intrinsically disordered
      protein that functions both in membrane adhesion, and as a linker connecting the
      oligodendrocyte membrane to the underlying cytoskeleton; its specific
      interactions with calmodulin and SH3-domain containing proteins suggest further
      multifunctionality in signaling. Here, we have used multidimensional
      heteronuclear nuclear magnetic resonance spectroscopy to study the conformational
      dependence on environment of the protein in aqueous solution (100 mM KCl) and in
      a membrane-mimetic solvent (30% TFE-d(2)), particularly to analyze its secondary
      structure using chemical shift indexing, and to investigate its backbone dynamics
      using (15)N spin relaxation measurements. Collectively, the data revealed three
      major segments of the protein with a propensity toward alpha-helicity that was
      stabilized by membrane-mimetic conditions: T33-D46, V83-T92, and T142-L154
      (murine 18.5 kDa sequence numbering). All of these regions corresponded with
      bioinformatics predictions of ordered secondary structure. The V83-T92 region
      comprises a primary immunodominant epitope that had previously been shown by site
      directed spin labeling and electron paramagnetic resonance spectroscopy to be
      alpha-helical in membrane-reconstituted systems. The T142-L154 segment overlapped
      with a predicted calmodulin-binding site. Chemical shift perturbation experiments
      using labeled MBP and unlabeled calmodulin demonstrated a dramatic conformational
      change in MBP upon association of the two proteins, and were consistent with the
      C-terminal segment of MBP being the primary binding site for calmodulin.

PMID- 18326634
TI  - Magnetic stimulation of one-dimensional neuronal cultures.
AB  - Transcranial magnetic stimulation is a remarkable tool for neuroscience research,
      with a multitude of diagnostic and therapeutic applications. Surprisingly,
      application of the same magnetic stimulation directly to neurons that are
      dissected from the brain and grown in vitro was not reported to activate them to
      date. Here we report that central nervous system neurons patterned on large
      enough one-dimensional rings can be magnetically stimulated in vitro. In
      contrast, two-dimensional cultures with comparable size do not respond to
      excitation. This happens because the one-dimensional pattern enforces an ordering
      of the axons along the ring, which is designed to follow the lines of the
      magnetically induced electric field. A small group of sensitive (i.e.,
      initiating) neurons respond even when the network is disconnected, and are
      presumed to excite the entire network when it is connected. This implies that
      morphological and electrophysiological properties of single neurons are crucial
      for magnetic stimulation. We conjecture that the existence of a select group of
      neurons with higher sensitivity may occur in the brain in vivo as well, with
      consequences for transcranial magnetic stimulation.

PMID- 18326635
TI  - Salt-mediated electrostatics in the association of TATA binding proteins to DNA:
      a combined molecular mechanics/Poisson-Boltzmann study.
AB  - The TATA-binding protein (TBP) is a key component of the archaea ternary
      preinitiation transcription assembly. The archaeon TBP, from the
      halophile/hyperthermophile organism Pyrococcus woesei, is adapted to high
      concentrations of salt and high-temperature environments. Although most
      eukaryotic TBPs are mesophilic and adapted to physiological conditions of
      temperature and salt, they are very similar to their halophilic counterparts in
      sequence and fold. However, whereas the binding affinity to DNA of halophilic
      TBPs increases with increasing salt concentration, the opposite is observed for
      mesophilic TBPs. We investigated these differences in nonspecific salt-dependent
      DNA-binding behavior of halophilic and mesophilic TBPs by using a combined
      molecular mechanics/Poisson-Boltzmann approach. Our results are qualitatively in
      good agreement with experimentally observed salt-dependent DNA-binding for
      mesophilic and halophilic TBPs, and suggest that the distribution and the total
      number of charged residues may be the main underlying contributor in the
      association process. Therefore, the difference in the salt-dependent binding
      behavior of mesophilic and halophilic TBPs to DNA may be due to the very unique
      charge and electrostatic potential distribution of these TBPs, which consequently
      alters the number of repulsive and attractive electrostatic interactions.

PMID- 18326636
TI  - The allosteric role of the Ca2+ switch in adhesion and elasticity of C-cadherin.
AB  - Modular proteins such as titin, fibronectin, and cadherin are ubiquitous
      components of living cells. Often involved in signaling and mechanical processes,
      their architecture is characterized by domains containing a variable number of
      heterogeneous "repeats" arranged in series, with either flexible or rigid linker
      regions that determine their elasticity. Cadherin repeats arranged in series are
      unique in that linker regions also feature calcium-binding motifs. While it is
      well known that the extracellular repeats of cadherin proteins mediate cell-cell
      adhesion in a calcium-dependent manner, the molecular mechanisms behind the
      influence of calcium in adhesion dynamics and cadherin's mechanical response are
      not well understood. Here we show, using molecular dynamics simulations, how
      calcium ions control the structural integrity of cadherin's linker regions,
      thereby affecting cadherin's equilibrium dynamics, the availability of key
      residues involved in cell-cell adhesion, and cadherin's mechanical response. The
      all-atom, multi-nanosecond molecular dynamics simulations involved the entire C
      cadherin extracellular domain solvated in water (a 345,000 atom system).
      Equilibrium simulations show that the extracellular domain maintains its crystal
      conformation (elongated and slightly curved) when calcium ions are present. In
      the absence of calcium ions, however, it assumes a disordered conformation. The
      conserved residue Trp(2), which is thought to insert itself into a hydrophobic
      pocket of another cadherin molecule (thereby providing the basis for cell-cell
      adhesion), switches conformation from exposed to intermittently buried upon
      removal of calcium ions. Furthermore, the overall mechanical response of C
      cadherin's extracellular domain is characterized at low force by changes in shape
      (tertiary structure elasticity), and at high force by unraveling of secondary
      structure elements (secondary structure elasticity). This mechanical response is
      modulated by calcium ions at both low and high force, switching from a stiff, rod
      like to a soft, spring-like behavior upon removal of ions. The simulations
      provide an unprecedented molecular view of calcium-mediated allostery in
      cadherins, also illustrating the general principles of linker-mediated elasticity
      of modular proteins relevant not only for cell-cell adhesion and sound
      transduction, but also muscle elasticity.

PMID- 18326637
TI  - Sustained oscillations in extended genetic oscillatory systems.
AB  - Various dynamic cellular behaviors have been successfully modeled in terms of
      elementary circuitries showing particular characteristics such as negative
      feedback loops for sustained oscillations. Given, however, the increasing
      evidences indicating that cellular components do not function in isolation but
      form a complex interwoven network, it is still unclear to what extent the
      conclusions drawn from the elementary circuit analogy hold for systems that are
      highly interacting with surrounding environments. In this article, we consider a
      specific example of genetic oscillator systems, the so-called repressilator, as a
      starting point toward a systematic investigation into the dynamic consequences of
      the extension through interlocking of elementary biological circuits. From in
      silico analyses with both continuous and Boolean dynamics approaches to the four
      node extension of the repressilator, we found that 1), the capability of
      sustained oscillation depends on the topology of extended systems; and 2), the
      stability of oscillation under the extension also depends on the coupling
      topology. We then deduce two empirical rules favoring the sustained oscillations,
      termed the coherent coupling and the homogeneous regulation. These simple rules
      will help us prioritize candidate patterns of network wiring, guiding both the
      experimental investigations for further physiological verification and the
      synthetic designs for bioengineering.

PMID- 18326638
TI  - Confirming the revised C-terminal domain of the MscL crystal structure.
AB  - The structure of the C-terminal domain of the mechanosensitive channel of large
      conductance (MscL) has generated significant controversy. As a result, several
      structures have been proposed for this region: the original crystal structure
      (1MSL) of the Mycobacterium tuberculosis homolog (Tb), a model of the Escherichia
      coli homolog, and, most recently, a revised crystal structure of Tb-MscL (2OAR).
      To understand which of these structures represents a physiological conformation,
      we measured the impact of mutations to the C-terminal domain on the thermal
      stability of Tb-MscL using circular dichroism and performed molecular dynamics
      simulations of the original and the revised crystal structures of Tb-MscL. Our
      results imply that this region is helical and adopts an alpha-helical bundle
      conformation similar to that observed in the E. coli MscL model and the revised
      Tb-MscL crystal structure.

PMID- 18326639
TI  - Initial reaction dynamics of proteorhodopsin observed by femtosecond infrared and
      visible spectroscopy.
AB  - We present a comparative study using femtosecond pump/probe spectroscopy in the
      visible and infrared of the early photodynamics of solubilized proteorhodopsin
      (green absorbing variant) in D(2)O with deprotonated (pD 9.2) and protonated (pD
      6.4) primary proton acceptor Asp-97. The vis-pump/vis-probe experiments show a
      kinetic isotope effect that is more pronounced for alkaline conditions, thus
      decreasing the previously reported pH-dependence of the primary reaction of
      proteorhodopsin in H(2)O. This points to a pH dependent H-bonding network in the
      binding pocket of proteorhodopsin, that directly influences the primary photo
      induced dynamics. The vis-pump/IR-probe experiments were carried out in two
      different spectral regions and allowed to monitor the retinal C=C (1500 cm(-1)
      1580 cm(-1)) and C=N stretching vibration as well as the amide I mode of the
      protein (1590 cm(-1)-1680 cm(-1)). Like the FTIR spectra of the K intermediate
      (PR(K)-PR difference spectra) in this spectral range, the kinetic parameters and
      also the quantum efficiency of photo-intermediate formation are found to be
      virtually independent of the pD value.

PMID- 18326640
TI  - Differences in internal dynamics of actin under different structural states
      detected by neutron scattering.
AB  - F-actin, a helical polymer formed by polymerization of the monomers (G-actin),
      plays crucial roles in various aspects of cell motility. Flexibility of F-actin
      has been suggested to be important for such a variety of functions. Understanding
      the flexibility of F-actin requires characterization of a hierarchy of dynamical
      properties, from internal dynamics of the actin monomers through domain motions
      within the monomers and relative motions between the monomers within F-actin to
      large-scale motions of F-actin as a whole. As a first step toward this ultimate
      purpose, we carried out elastic incoherent neutron scattering experiments on
      powders of F-actin and G-actin hydrated with D(2)O and characterized the internal
      dynamics of F-actin and G-actin. Well established techniques and analysis enabled
      the extraction of mean-square displacements and their temperature dependence in F
      actin and in G-actin. An effective force constant analysis with a model
      consisting of three energy states showed that two dynamical transitions occur at
      approximately 150 K and approximately 245 K, the former of which corresponds to
      the onset of anharmonic motions and the latter of which couples with the
      transition of hydration water. It is shown that behavior of the mean-square
      displacements is different between G-actin and F-actin, such that G-actin is
      "softer" than F-actin. The differences in the internal dynamics are detected for
      the first time between the different structural states (the monomeric state and
      the polymerized state). The different behavior observed is ascribed to the
      differences in dynamical heterogeneity between F-actin and G-actin. Based on
      structural data, the assignment of the differences observed in the two samples to
      dynamics of specific loop regions involved in the polymerization of G-actin into
      F-actin is proposed.

PMID- 18326641
TI  - Global and local structural changes of cytochrome c and lysozyme characterized by
      a multigroup unfolding process.
AB  - Equilibrium unfolding behaviors of cytochrome c and lysozyme induced by the
      presence of urea (0-10 M) as well as changes in temperature (295-363 K) or pH
      (1.8-7) are examined via small-angle x-ray scattering and spectroscopic
      techniques, including circular dichroism and optical absorption. Denaturant and
      temperature effects are incorporated into the free energy expression for a
      general multigroup unfolding process. Results indicate that there are at least
      four unfolding groups in the temperature-, urea-, or pH-induced unfolding of
      cytochrome c: two of these are related to the prosthetic heme group, and the
      other two correspond, respectively, to the unfolding of alpha-helices and global
      changes in protein morphology that are largely unaccounted for by the first two
      groups. In contrast, the unfolding of lysozyme approximately follows a simple one
      group process. A modified mean-field Ising model is adopted for a coherent
      description of the unfolding behaviors observed. Thermodynamic parameters
      extracted from simple denaturing processes, on the basis of the Ising model, can
      closely predict unfolding behaviors of the proteins in compounded denaturing
      environments.

PMID- 18326642
TI  - Label-free, high-throughput measurements of dynamic changes in cell nuclei using
      angle-resolved low coherence interferometry.
AB  - Accurate measurements of nuclear deformation, i.e., structural changes of the
      nucleus in response to environmental stimuli, are important for signal
      transduction studies. Traditionally, these measurements require labeling and
      imaging, and then nuclear measurement using image analysis. This approach is time
      consuming, invasive, and unavoidably perturbs cellular systems. Light scattering,
      an emerging biophotonics technique for probing physical characteristics of living
      systems, offers a promising alternative. Angle-resolved low-coherence
      interferometry (a/LCI), a novel light scattering technique, was developed to
      quantify nuclear morphology for early cancer detection. In this study, a/LCI is
      used for the first time to noninvasively measure small changes in nuclear
      morphology in response to environmental stimuli. With this new application, we
      broaden the potential uses of a/LCI by demonstrating high-throughput measurements
      and by probing aspherical nuclei. To demonstrate the versatility of this
      approach, two distinct models relevant to current investigations in cell and
      tissue engineering research are used. Structural changes in cell nuclei due to
      subtle environmental stimuli, including substrate topography and osmotic
      pressure, are profiled rapidly without disrupting the cells or introducing
      artifacts associated with traditional measurements. Accuracy > or = 3% is
      obtained for the range of nuclear geometries examined here, with the greatest
      deviations occurring for the more complex geometries. Given the high-throughput
      nature of the measurements, this deviation may be acceptable for many biological
      applications that seek to establish connections between morphology and function.

PMID- 18326643
TI  - Interaction of LL-37 with model membrane systems of different complexity:
      influence of the lipid matrix.
AB  - As the main difference between bacterial and mammalian cell membranes is their
      net charge, the focal point of consideration in many model membrane experiments
      with antimicrobial peptides is lipid headgroup charge. We studied the interaction
      of the human multifunctional peptide LL-37 with single phospholipid monolayers,
      bilayers, and bilayers composed of binary mixtures of the four phospholipid
      species predominantly used in model membrane experiments (phosphatidylcholine,
      phosphatidylethanolamine, phosphatidylglycerol, and phosphatidylserine). We found
      that 1), the effects on single lipid monolayers are not comparable to those on
      the corresponding bilayers; 2), there are four different effects of LL-37 on
      bilayers of the four lipids; 3), the preference of LL-37 for the specific lipids
      is roughly inversely related to chain packing density; and 4), in the binary
      lipid mixtures, one lipid-and not necessarily the charged one--generally governs
      the mode of lipid/peptide interaction. Thus, our results show that lipid net
      charge is not the decisive factor determining the membrane-perturbing mechanism
      of LL-37, but only one of several parameters, among them packing density, the
      ability to form intermolecular H-bonds, and lipid molecular shape, which
      emphasizes how profoundly the choice of the model system can influence the
      outcome of a study of lipid/peptide interaction.

PMID- 18326644
TI  - Observation of noncooperative folding thermodynamics in simulations of 1BBL.
AB  - One of the predictions of the energy landscape theory of protein folding is the
      possibility of barrierless, "downhill" folding under certain conditions. The
      protein 1BBL has been proposed to fold by such a downhill mechanism, though this
      is a matter of some dispute. We carried out extensive replica exchange molecular
      dynamics simulations on 1BBL in explicit solvent to address this controversy and
      provide a microscopic picture of its folding thermodynamics. Our simulations show
      two distinct structural transitions in the folding of 1BBL. A low-temperature
      transition involves a disordering of the protein's tertiary structure without
      loss of secondary structure. A distinct, higher temperature transition involves
      the complete loss of secondary structure and dissolution of the hydrophobic core.
      In contrast, control simulations of the 1BBL homolog E3BD show a single high
      temperature unfolding transition. Further simulations of 1BBL at high ionic
      strength show a significant destabilization of helix II but not helix I,
      suggesting that the apparent folding cooperativity of 1BBL may be highly
      dependent on experimental conditions. Although our simulations cannot provide
      definitive evidence of downhill folding in 1BBL, they clearly show evidence of a
      complex, non-two-state folding process.

PMID- 18326645
TI  - Simulation-based fitting of protein-protein interaction potentials to SAXS
      experiments.
AB  - We present a new method for computing interaction potentials of solvated proteins
      directly from small-angle x-ray scattering data. An ensemble of proteins is
      modeled by Monte Carlo or molecular dynamics simulation. The global x-ray
      scattering of the whole model ensemble is then computed at each snapshot of the
      simulation, and averaged to obtain the x-ray scattering intensity. Finally, the
      interaction potential parameters are adjusted by an optimization algorithm, and
      the procedure is iterated until the best agreement between simulation and
      experiment is obtained. This new approach obviates the need for approximations
      that must be made in simplified analytical models. We apply the method to lambda
      repressor fragment 6-85 and fyn-SH3. With the increased availability of fast
      computer clusters, Monte Carlo and molecular dynamics analysis using residue
      level or even atomistic potentials may soon become feasible.

PMID- 18326646
TI  - An entropic perspective of protein stability on surfaces.
AB  - The interaction of proteins with surfaces regulates numerous processes in nature,
      science, and technology. In many applications, it is desirable to place proteins
      on surfaces in an active state, and tethering represents one manner in which to
      accomplish this. However, a clear understanding of how tether placement and
      design affects protein activity is lacking. Available theoretical models predict
      that proteins will be stabilized when tethered to substrates. Such models suggest
      that the surface reduces the number of states accessible to the unfolded state of
      the protein, thereby reducing the entropic cost of folding on the surface
      compared to the bulk case. Recent studies, however, have shown that this
      stabilization is not always seen. The purpose of this article is to determine the
      validity of the theory with a thorough thermodynamic analysis of the folding of
      peptides attached to surfaces. Configuration-temperature-density-of-states Monte
      Carlo simulations are used to examine the behavior of four different peptides of
      different secondary and tertiary structure. It is found that the surface does
      reduce the entropic cost of folding for tethered peptides, as the theory
      suggests. This effect, however, does not always translate into improved stability
      because the surface may also have a destabilizing enthalpic effect. The theory
      neglects this effect and assumes that the enthalpy of folding is the same on and
      off the surface. Both the enthalpic and entropic contributions to the stability
      are found to be topology- and tether-placement-specific; we show that stability
      cannot be predicted a priori. A detailed analysis of the folding of protein A
      shows how the same protein can be both stabilized and destabilized on a surface
      depending upon how the tethering enhances or hinders the ability of the peptide
      to form correct tertiary structures.

PMID- 18326647
TI  - Structure of the cytosolic part of the subunit b-dimer of Escherichia coli F0F1
      ATP synthase.
AB  - The structure of the external stalk and its function in the catalytic mechanism
      of the F(0)F(1)-ATP synthase remains one of the important questions in
      bioenergetics. The external stalk has been proposed to be either a rigid stator
      that binds F(1) or an elastic structural element that transmits energy from the
      small rotational steps of subunits c to the F(1) sector during catalysis. We
      employed proteomics, sequence-based structure prediction, molecular modeling, and
      electron spin resonance spectroscopy using site-directed spin labeling to
      understand the structure and interfacial packing of the Escherichia coli b
      subunit homodimer external stalk. Comparisons of bacterial, cyanobacterial, and
      plant b-subunits demonstrated little sequence similarity. Supersecondary
      structure predictions, however, show that all compared b-sequences have extensive
      heptad repeats, suggesting that the proteins all are capable of packing as left
      handed coiled-coils. Molecular modeling subsequently indicated that b(2) from the
      E. coli ATP synthase could pack into stable left-handed coiled-coils. Thirty
      eight substitutions to cysteine in soluble b-constructs allowed the introduction
      of spin labels and the determination of intersubunit distances by ESR. These
      distances correlated well with molecular modeling results and strongly suggest
      that the E. coli subunit b-dimer can stably exist as a left-handed coiled-coil.

PMID- 18326648
TI  - Subunit b-dimer of the Escherichia coli ATP synthase can form left-handed coiled
      coils.
AB  - One remaining challenge to our understanding of the ATP synthase concerns the
      dimeric coiled-coil stator subunit b of bacterial synthases. The subunit b-dimer
      has been implicated in important protein interactions that appear necessary for
      energy conservation and that may be instrumental in energy conservation during
      rotary catalysis by the synthase. Understanding the stator structure and its
      interactions with the rest of the enzyme is crucial to the understanding of the
      overall catalytic mechanism. Controversy exists on whether subunit b adopts a
      classic left-handed or a presumed right-handed dimeric coiled-coil and whether or
      not staggered pairing between nonhomologous residues in the homodimer is required
      for intersubunit packing. In this study we generated molecular models of the
      Escherichia coli subunit b-dimer that were based on the well-established heptad
      repeat packing exhibited by left-handed, dimeric coiled-coils by employing
      simulated annealing protocols with structural restraints collected from known
      structures. In addition, we attempted to create hypothetical right-handed coiled
      coil models and left- and right-handed models with staggered packing in the
      coiled-coil domains. Our analyses suggest that the available structural and
      biochemical evidence for subunit b can be accommodated by classic left-handed,
      dimeric coiled-coil quaternary structures.

PMID- 18326649
TI  - I5S: wide-field light microscopy with 100-nm-scale resolution in three
      dimensions.
AB  - A new type of wide-field fluorescence microscopy is described, which produces 100
      nm-scale spatial resolution in all three dimensions, by using structured
      illumination in a microscope that has two opposing objective lenses. Illumination
      light is split by a grating and a beam splitter into six mutually coherent beams,
      three of which enter the specimen through each objective lens. The resulting
      illumination intensity pattern contains high spatial frequency components both
      axially and laterally. In addition, the emission is collected by both objective
      lenses coherently, and combined interferometrically on a single camera, resulting
      in a detection transfer function with axially extended support. These two effects
      combine to produce near-isotropic resolution. Experimental images of test samples
      and biological specimens confirm the theoretical predictions.

PMID- 18326650
TI  - Three-dimensional resolution doubling in wide-field fluorescence microscopy by
      structured illumination.
AB  - Structured illumination microscopy is a method that can increase the spatial
      resolution of wide-field fluorescence microscopy beyond its classical limit by
      using spatially structured illumination light. Here we describe how this method
      can be applied in three dimensions to double the axial as well as the lateral
      resolution, with true optical sectioning. A grating is used to generate three
      mutually coherent light beams, which interfere in the specimen to form an
      illumination pattern that varies both laterally and axially. The spatially
      structured excitation intensity causes normally unreachable high-resolution
      information to become encoded into the observed images through spatial frequency
      mixing. This new information is computationally extracted and used to generate a
      three-dimensional reconstruction with twice as high resolution, in all three
      dimensions, as is possible in a conventional wide-field microscope. The method
      has been demonstrated on both test objects and biological specimens, and has
      produced the first light microscopy images of the synaptonemal complex in which
      the lateral elements are clearly resolved.

PMID- 18326651
TI  - Using fluorescence correlation spectroscopy to study conformational changes in
      denatured proteins.
AB  - Fluorescence correlation spectroscopy (FCS) is a sensitive analytical tool that
      allows dynamics and hydrodynamics of biomolecules to be studied under a broad
      range of experimental conditions. One application of FCS of current interest is
      the determination of the size of protein molecules in the various states they
      sample along their folding reaction coordinate, which can be accessed through the
      measurement of diffusion coefficients. It has been pointed out that the analysis
      of FCS curves is prone to artifacts that may lead to erroneous size
      determination. To set the stage for FCS studies of unfolded proteins, we first
      show that the diffusion coefficients of small molecules as well as proteins can
      be determined accurately even in the presence of high concentrations of co
      solutes that change the solution refractive index significantly. Indeed, it is
      found that the Stokes-Einstein relation between the measured diffusion
      coefficient and solution viscosity holds even in highly concentrated glycerol or
      guanidinium hydrochloride (GuHCl) solutions. These measurements form the basis
      for an investigation of the structure of the denatured state of two proteins, the
      small protein L and the larger, three-domain protein adenylate kinase (AK). FCS
      is found useful for probing expansion in the denatured state beyond the unfolding
      transition. It is shown that the denatured state of protein L expands as the
      denaturant concentration increases, in a process akin to the transition from a
      globule to a coil in polymers. This process continues at least up to 5 M GuHCl.
      On the other hand, the denatured state of AK does not seem to expand much beyond
      2 M GuHCl, a result that is in qualitative accord with single-molecule
      fluorescence histograms. Because both the unfolding transition and the coil
      globule transition of AK occur at a much lower denaturant concentration than
      those of protein L, a possible correlation between the two phenomena is
      suggested.

PMID- 18326652
TI  - Arp2/3 controls the motile behavior of N-WASP-functionalized GUVs and modulates N
      WASP surface distribution by mediating transient links with actin filaments.
AB  - Spatially controlled assembly of actin in branched filaments generates cell
      protrusions or the propulsion of intracellular vesicles and pathogens. The
      propulsive movement of giant unilamellar vesicles (GUVs) functionalized by N-WASP
      (full-length or truncated) is reconstituted in a biochemically controlled medium,
      and analyzed using phase contrast and fluorescence microscopy to elucidate the
      links between membrane components and the actin cytoskeleton that determine
      motile behavior. Actin-based propulsion displays a continuous regime or a
      periodic saltatory regime. The transition between the two regimes is controlled
      by the concentration of Arp2/3 complex, which branches filaments by interacting
      with N-WASP at the liposome surface. Saltatory motion is linked to cycles in the
      distribution of N-WASP at the membrane between a homogeneous and a segregated
      state. Comparison of the changes in distribution of N-WASP, Arp2/3, and actin
      during propulsion demonstrates that actin filaments bind to N-WASP, and that
      these bonds are transitory. This interaction, mediated by Arp2/3, drives N-WASP
      segregation. VC-fragments of N-WASP, that interact more weakly than N-WASP with
      the Arp2/3 complex, segregate less than N-WASP at the rear of the GUVs. GUV
      propulsion is inhibited by the presence of VCA-actin covalent complex, showing
      that the release of actin from the nucleator is required for movement. The
      balance between segregation and free diffusion determines whether continuous
      movement can be sustained. Computed surface distributions of N-WASP, derived from
      a theoretical description of this segregation-diffusion mechanism, account
      satisfactorily for the measured density profiles of N-WASP, Arp2/3 complex, and
      actin.

PMID- 18326653
TI  - Spectroscopic and molecular dynamics evidence for a sequential mechanism for the
      A-to-B transition in DNA.
AB  - The A-to-B form transition has been examined in three DNA duplexes,
      d(CGCGAATTCGCG)(2), d(CGCGAATTGCGC), and d(CGCAAATTTCGC), using circular
      dichroism spectroscopy, ultraviolet resonance Raman (UVRR) spectroscopy, and
      molecular dynamics (MD) simulation. Circular dichroism spectra confirm that these
      molecules adopt the A form under conditions of reduced water activity. UVRR
      results, obtained under similar conditions, suggest that the transition involves
      a series of intermediate forms between A and B. Cooperative and distinct
      transitions were observed for the bases and the sugars. Independent MD
      simulations on d(CGCGAATTCGCG)(2) show a spontaneous change from the A to B form
      in aqueous solution and describe a kinetic model that agrees well with UVRR
      results. Based on these observations, we predict that the mechanism of the
      transition involves a series of A/B hybrid forms and is sequential in nature,
      similar to previous crystallographic studies of derivatized duplexes. A
      simulation in which waters were restrained in the major groove of B DNA shows a
      rapid, spontaneous change from B to A at reduced water activity. These results
      indicate that a quasiergodic sampling of the solvent distribution may be a
      problem in going from B to A at reduced water activity in the course of an MD
      simulation.

PMID- 18326654
TI  - Characteristics of nucleosome core DNA and their applications in predicting
      nucleosome positions.
AB  - By analyzing dinucleotide position-frequency data of yeast nucleosome-bound DNA
      sequences, dinucleotide periodicities of core DNA sequences were investigated.
      Within frequency domains, weakly bound dinucleotides (AA, AT, and the
      combinations AA-TT-TA and AA-TT-TA-AT) present doublet peaks in a periodicity
      range of 10-11 bp, and strongly bound dinucleotides present a single peak. A time
      frequency analysis, based on wavelet transformation, indicated that weakly bound
      dinucleotides of core DNA sequences were spaced smaller (approximately 10.3 bp)
      at the two ends, with larger (approximately 11.1 bp) spacing in the middle
      section. The finding was supported by DNA curvature and was prevalent in all core
      DNA sequences. Therefore, three approaches were developed to predict nucleosome
      positions. After analyzing a 2200-bp DNA sequence, results indicated that the
      predictions were feasible; areas near protein-DNA binding sites resulted in
      periodicity profiles with irregular signals. The effects of five dinucleotide
      patterns were evaluated, indicating that the AA-TT pattern exhibited better
      performance. A chromosome-scale prediction demonstrated that periodicity profiles
      perform better than previously described, with up to 59% accuracy. Based on
      predictions, nucleosome distributions near the beginning and end of open reading
      frames were analyzed. Results indicated that the majority of open reading frames'
      start and end sites were occupied by nucleosomes.

PMID- 18326656
TI  - Metabolic fluxes and stoichiometry of glucose metabolism.

PMID- 18326657
TI  - The Mycobacterium tuberculosis virulence factor trehalose dimycolate imparts
      desiccation resistance to model mycobacterial membranes.
AB  - Mycobacteria, including persistent pathogens like Mycobacterium tuberculosis,
      have an unusual membrane structure in which, outside the plasma membrane, a
      nonfluid hydrophobic fatty acid layer supports a fluid monolayer rich in
      glycolipids such as trehalose 6,6'-dimycolate (TDM; cord factor). Given the
      abilities of mycobacteria to survive desiccation and trehalose in solution to
      protect biomolecules and whole organisms during freezing, drying, and other
      stresses, we hypothesized that TDM alone may suffice to confer dehydration
      resistance to the membranes of which it is a constituent. We devised an
      experimental model that mimics the structure of mycobacterial envelopes in which
      an immobile hydrophobic layer supports a TDM-rich, two-dimensionally fluid
      leaflet. We have found that TDM monolayers, in stark contrast to phospholipid
      membranes, can be dehydrated and rehydrated without loss of integrity, as
      assessed by fluidity and protein binding. Strikingly, this protection from
      dehydration extends to TDM-phospholipid mixtures with as little as 25 mol % TDM.
      The dependence of the recovery of membrane mobility upon rehydration on TDM
      fraction shows a functional form indicative of spatial percolation, implying that
      the connectivity of TDM plays a crucial role in membrane preservation. Our
      observations are the first reported instance of dehydration resistance provided
      by a membrane glycolipid.

PMID- 18326658
TI  - Fluorescence recovery after photobleaching: the case of anomalous diffusion.
AB  - The method of FRAP (fluorescence recovery after photobleaching), which has been
      broadly used to measure lateral mobility of fluorescent-labeled molecules in cell
      membranes, is formulated here in terms of continuous time random walks (CTRWs),
      which offer both analytical expressions and a scheme for numerical simulations.
      We propose an approach based on the CTRW and the corresponding fractional
      diffusion equation (FDE) to analyze FRAP results in the presence of anomalous
      subdiffusion. The FDE generalizes the simple diffusive picture, which has been
      applied to FRAP when assuming regular diffusion, to account for subdiffusion. We
      use a subordination relationship between the solutions of the fractional and
      normal diffusion equations to fit FRAP recovery curves obtained from CTRW
      simulations, and compare the fits to the commonly used approach based on the
      simple diffusion equation with a time dependent diffusion coefficient (TDDC). The
      CTRW and TDDC describe two different dynamical schemes, and although the CTRW
      formalism appears to be more complicated, it provides a physical description that
      underlies anomalous lateral diffusion.

PMID- 18326659
TI  - Micropatterning of single endothelial cell shape reveals a tight coupling between
      nuclear volume in G1 and proliferation.
AB  - Shape-dependent local differentials in cell proliferation are considered to be a
      major driving mechanism of structuring processes in vivo, such as embryogenesis,
      wound healing, and angiogenesis. However, the specific biophysical signaling by
      which changes in cell shape contribute to cell cycle regulation remains poorly
      understood. Here, we describe our study of the roles of nuclear volume and
      cytoskeletal mechanics in mediating shape control of proliferation in single
      endothelial cells. Micropatterned adhesive islands were used to independently
      control cell spreading and elongation. We show that, irrespective of elongation,
      nuclear volume and apparent chromatin decondensation of cells in G1
      systematically increased with cell spreading and highly correlated with DNA
      synthesis (percent of cells in the S phase). In contrast, cell elongation
      dramatically affected the organization of the actin cytoskeleton, markedly
      reduced both cytoskeletal stiffness (measured dorsally with atomic force
      microscopy) and contractility (measured ventrally with traction microscopy), and
      increased mechanical anisotropy, without affecting either DNA synthesis or
      nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of
      the proliferative status of single endothelial cells within a population, whereas
      cell stiffness and contractility are not. These findings show that the effects of
      cell mechanics in shape control of proliferation are far more complex than a
      linear or straightforward relationship. Our data are consistent with a mechanism
      by which spreading of cells in G1 partially enhances proliferation by inducing
      nuclear swelling and decreasing chromatin condensation, thereby rendering DNA
      more accessible to the replication machinery.

PMID- 18326660
TI  - Prokaryotic gene finding based on physicochemical characteristics of codons
      calculated from molecular dynamics simulations.
AB  - An ab initio model for gene prediction in prokaryotic genomes is proposed based
      on physicochemical characteristics of codons calculated from molecular dynamics
      (MD) simulations. The model requires a specification of three calculated
      quantities for each codon: the double-helical trinucleotide base pairing energy,
      the base pair stacking energy, and an index of the propensity of a codon for
      protein-nucleic acid interactions. The base pairing and stacking energies for
      each codon are obtained from recently reported MD simulations on all unique
      tetranucleotide steps, and the third parameter is assigned based on the conjugate
      rule previously proposed to account for the wobble hypothesis with respect to
      degeneracies in the genetic code. The third interaction propensity parameter
      values correlate well with ab initio MD calculated solvation energies and
      flexibility of codon sequences as well as codon usage in genes and amino acid
      composition frequencies in approximately 175,000 protein sequences in the
      Swissprot database. Assignment of these three parameters for each codon enables
      the calculation of the magnitude and orientation of a cumulative three
      dimensional vector for a DNA sequence of any length in each of the six genomic
      reading frames. Analysis of 372 genomes comprising approximately 350,000 genes
      shows that the orientations of the gene and nongene vectors are well
      differentiated and make a clear distinction feasible between genic and nongenic
      sequences at a level equivalent to or better than currently available knowledge
      based models trained on the basis of empirical data, presenting a strong support
      for the possibility of a unique and useful physicochemical characterization of
      DNA sequences from codons to genomes.

PMID- 18326661
TI  - Controlled aggregation of ferritin to modulate MRI relaxivity.
AB  - Ferritin is an iron storage protein expressed in varying concentrations in
      mammalian cells. The deposition of ferric iron in the core of ferritin makes it a
      magnetic resonance imaging contrast agent, and ferritin has recently been
      proposed as a gene expression reporter protein for magnetic resonance imaging. To
      date, ferritin has been overexpressed in vivo and has been coexpressed with
      transferrin receptor to increase iron loading in cells. However, ferritin has a
      relatively low T(2) relaxivity (R(2) approximately 1 mM(-1)s(-1)) at typical
      magnetic field strengths and so requires high levels of expression to be
      detected. One way to modulate the transverse relaxivity of a superparamagnetic
      agent is to cause it to aggregate, thereby manipulating the magnetic field
      gradients through which water diffuses. In this work, it is demonstrated by
      computer simulation and in vitro that aggregation of ferritin can alter
      relaxivity. The effects of aggregate size and intraaggregate perturber spacing on
      R(2) are studied. Computer modeling indicates that the optimal spacing of the
      ferritin molecules in aggregate for increasing R(2) is 100-200 nm for a typical
      range of water diffusion rates. Chemical cross-linking of ferritin at 12 A
      spacing led to a 70% increase in R(2) compared to uncross-linked ferritin
      controls. To modulate ferritin aggregation in a potentially biologically relevant
      manner, ferritin was attached to actin and polymerized in vitro. The
      polymerization of ferritin-F-actin caused a 20% increase in R(2) compared to
      unpolymerized ferritin-G-actin. The R(2)-value was increased by another 10% by
      spacing the ferritin farther apart on the actin filaments. The modulation of
      ferritin aggregation by binding to cytoskeletal elements may be a useful strategy
      to make a functional reporter gene for magnetic resonance imaging.

PMID- 18326662
TI  - Real-time cross-correlation image analysis of early events in IgE receptor
      signaling.
AB  - Signaling in mast cells and basophils is mediated through IgE and its high
      affinity cell surface receptor, FcepsilonRI. Crosslinking of the receptors by a
      cognate multivalent antigen leads to degranulation and release of mediators of
      the allergic immune response. Using multicolor fluorescence confocal microscopy,
      we probed the spatio-temporal dynamics of early events in the IgE receptor signal
      cascade. We monitored the recruitment of GFP-/CFP-labeled signaling proteins by
      acquiring sequential images with time resolution of 3 s during stimulation of RBL
      2H3 mast cells with multivalent antigen. A fluorescent tag on the antigen allowed
      us to visualize the plasma membrane localization of crosslinked receptors, and
      fluorescent cholera toxin B served as a plasma membrane marker. We developed an
      automated image analysis scheme to quantify the recruitment of fluorescent
      intracellular proteins to the plasma membrane and to assess the time-dependent
      colocalization of these and other membrane-associated proteins with crosslinked
      receptors as measured by cross-correlation between the plasma membrane
      distributions of the two fluorophores. This automated method permits analysis of
      thousands of individual images from multiple experiments for each cross
      correlation pair. We systematically applied this analysis to characterize
      stimulated interactions of IgE receptors with several signaling proteins,
      including the tyrosine kinases Lyn and Syk, and the adaptor protein LAT. Notably,
      for Syk-CFP we observed a rapid stimulated translocation to the plasma membrane
      but very little colocalization with aggregated receptors. Our results demonstrate
      the utility of this simple, automated method to monitor protein interactions
      quantitatively during cell signaling.

PMID- 18326663
TI  - AFM study on the electric-field effects on supported bilayer lipid membranes.
AB  - Electric-field induced changes in structure and conductivity of supported bilayer
      lipid membranes (SLM) have been studied at submicroscopic resolution using atomic
      force microscopy and electrochemical impedance spectroscopy. The SLMs are formed
      on gold surfaces modified with mixed self-assembled monolayers of a cholesterol
      tether and 6-mercaptohexanol. At applied potentials of < or =-0.25 V versus
      standard hydrogen electrode, the conductance of the SLM increases and membrane
      areas of <150 nm in size are found to elevate from the surface up to 15 nm in
      height. To estimate the electric field experienced by the lipid membrane,
      electrowetting has been used to determine the point of zero charge of a 6
      mercaptohexanol-modified surface (0.19 +/- 0.13 V versus standard hydrogen
      electrode). The effects of electric fields on the structure and conductance of
      supported membranes are discussed.

PMID- 18326664
TI  - ARVC-related mutations in divergent region 3 alter functional properties of the
      cardiac ryanodine receptor.
AB  - Two single-nucleotide polymorphisms in the type 2 ryanodine receptor (RyR2)
      leading to the nonsynonymous amino acid replacements G1885E and G1886S are
      associated with arrhythmogenic right ventricular cardiomyopathy in patients who
      are carrying both of the corresponding RyR2 alleles. The functional properties of
      HEK293 cell lines isogenically expressing RyR2 mutants associated with
      arrhythmogenic right ventricular cardiomyopathy, RyR2-G1885E, RyR2-G1886S, RyR2
      G1886D (mimicking a constitutively phosphorylated Ser(1886)), and the double
      mutant RyR2-G1885E/G1886S were investigated by analyzing the intracellular Ca(2+)
      release activity resulting from store-overload-induced calcium release. The
      substitution of serine for Gly(1886) caused a significant increase in the
      cellular Ca(2+) oscillation activity compared with RyR2 wild-type-expressing
      HEK293 cells. It was even more pronounced if glycine 1885 or 1886 was replaced by
      the acidic amino acids glutamate (G1885E) or aspartate (G1886D). Surprisingly,
      when both substitutions were introduced in the same RyR2 subunit (RyR2
      G1885E/G1886S), the store-overload-induced calcium release activity was nearly
      completely abolished, although the Ca(2+) loading of the intracellular stores was
      markedly enhanced, and the channel still displayed substantial Ca(2+) release on
      stimulation by 5 mM caffeine. These results suggest that the adjacent glycines
      1885 and 1886, located in the divergent region 3, are critical for the function
      and regulation of RyR2.

PMID- 18326665
TI  - Primary charge separation in the photosystem II core from Synechocystis: a
      comparison of femtosecond visible/midinfrared pump-probe spectra of wild-type and
      two P680 mutants.
AB  - It is now quite well accepted that charge separation in PS2 reaction centers
      starts predominantly from the accessory chlorophyll B(A) and not from the special
      pair P(680). To identify spectral signatures of B(A,) and to further clarify the
      process of primary charge separation, we compared the femtosecond-infrared pump
      probe spectra of the wild-type (WT) PS2 core complex from the cyanobacterium
      Synechocystis sp. PCC 6803 with those of two mutants in which the histidine
      residue axially coordinated to P(B) (D2-His(197)) has been changed to Ala or Gln.
      By analogy with the structure of purple bacterial reaction centers, the mutated
      histidine is proposed to be indirectly H-bonded to the C(9)=O carbonyl of the
      putative primary donor B(A) through a water molecule. The constructed mutations
      are thus expected to perturb the vibrational properties of B(A) by modifying the
      hydrogen bond strength, possibly by displacing the H-bonded water molecule, and
      to modify the electronic properties and the charge localization of the oxidized
      donor P(680)(+). Analysis of steady-state light-induced Fourier transform
      infrared difference spectra of the WT and the D2-His(197)Ala mutant indeed shows
      that a modification of the axially coordinating ligand to P(B) induces a charge
      redistribution of P(680)(+). In addition, a comparison of the time-resolved
      visible/midinfrared spectra of the WT and mutants has allowed us to investigate
      the changes in the kinetics of primary charge separation induced by the mutations
      and to propose a band assignment identifying the characteristic vibrations of
      B(A).

PMID- 18326666
TI  - Amplification of diacylglycerol activation of protein kinase C by cholesterol.
AB  - The combined effects of cholesterol, a major cell membrane component, and the
      lipid second messenger diacylglycerol on the activity of protein kinase C (PK-C)
      and the structure of phosphatidylcholine/phosphatidylserine bilayers were
      investigated using specific PK-C assays and (2)H NMR. Whereas the classical
      activation of PK-C was observed as an effect of diacylglycerol, in the absence of
      this second messenger, cholesterol did not affect PK-C activity. A novel effect
      of amplified PK-C activation was observed in the presence of both cholesterol and
      diacylglycerol concentrations within the physiological range of each of these
      components. (2)H NMR results suggest that this phenomenon is due to cholesterol-
      and diacylglycerol-induced increased propensity of the lipids to adopt nonbilayer
      phases, effectively destabilizing the bilayer structure. The magnitude of the
      effect was a function of cholesterol concentration, implying that laterally
      separated cell membrane domains with distinct cholesterol concentrations have the
      capacity to differ in their sensitivity to extracellular stimuli.

PMID- 18326667
TI  - Mechanical and biochemical modeling of cortical oscillations in spreading cells.
AB  - Actomyosin-based cortical contractility is a common feature of eukaryotic cells
      and is involved in cell motility, cell division, and apoptosis. In nonmuscle
      cells, oscillations in contractility are induced by microtubule depolymerization
      during cell spreading. We developed an ordinary differential equation model to
      describe this behavior. The computational model includes 36 parameters. The
      values for all but two of the model parameters were taken from experimental
      measurements found in the literature. Using these values, we demonstrate that the
      model generates oscillatory behavior consistent with current experimental
      observations. The rhythmic behavior occurs because of the antagonistic effects of
      calcium-induced contractility and stretch-activated calcium channels. The model
      makes several experimentally testable predictions: 1), buffering intracellular
      calcium increases the period and decreases the amplitude of cortical
      oscillations; 2), increasing the number or activity of stretch activated channels
      leads to an increase in period and amplitude of cortical oscillations; 3),
      inhibiting Ca(2+) pump activity increases the period and amplitude of
      oscillations; and 4), a threshold exists for the calcium concentration below
      which oscillations cease.

PMID- 18326668
TI  - Global response to desiccation stress in the soil actinomycete Rhodococcus jostii
      RHA1.
AB  - Rhodococcus jostii RHA1 is a soil-residing actinomycete with many favorable
      metabolic capabilities that make it an ideal candidate for the bioremediation of
      contaminated soils. Arguably the most basic requirement for life is water, yet
      some nonsporulating bacteria, like RHA1, can survive lengthy droughts. Here we
      report the first transcriptomic analysis of a gram-positive bacterium during
      desiccation. Filtered RHA1 cells incubated at either low relative humidity (20%),
      as an air-drying treatment, or high relative humidity (100%), as a control, were
      transcriptionally profiled over a comprehensive time series. Also, the morphology
      of RHA1 cells was characterized by cryofixation scanning electron microscopy
      during each treatment. Desiccation resulted in a transcriptional response of
      approximately 8 times more differentially regulated genes than in the control
      (819 versus 106 genes, respectively). Genes that were differentially expressed
      during only the desiccation treatment primarily had expression profiles that were
      maximally up-regulated upon complete drying of the cells. The microarray
      expression ratios for some of the highly up-regulated genes were verified by
      reverse transcriptase quantitative PCR. These genes included dps1, encoding an
      oxidative stress protection protein which has not previously been directly
      associated with desiccation, and the two genes encoding sigma factors SigF1 and
      SigF3, possibly involved in the regulatory response to desiccation. RHA1 cells
      also induced the biosynthetic pathway for the compatible solute ectoine. These
      desiccation-specific responses represent the best candidates for important
      mechanisms of desiccation resistance in RHA1.

PMID- 18326669
TI  - Cysteine scanning mutagenesis of alpha4, a putative pore-lining helix of the
      Bacillus thuringiensis insecticidal toxin Cry1Aa.
AB  - Helix alpha4 of Bacillus thuringiensis Cry toxins is thought to line the lumen of
      the pores they form in the midgut epithelial cells of susceptible insect larvae.
      To define its functional role in pore formation, most of the alpha4 amino acid
      residues were replaced individually by a cysteine in the Cry1Aa toxin. The
      toxicities and pore-forming abilities of the mutated toxins were examined,
      respectively, by bioassays using neonate Manduca sexta larvae and by a light
      scattering assay using midgut brush border membrane vesicles isolated from M.
      sexta. A majority of these mutants had considerably reduced toxicities and pore
      forming abilities. Most mutations causing substantial or complete loss of
      activity map on the hydrophilic face of the helix, while most of those having
      little or only relatively minor effects map on its hydrophobic face. The
      properties of the pores formed by mutants that retain significant activity appear
      similar to those of the pores formed by the wild-type toxin, suggesting that
      mutations resulting in a loss of activity interfere mainly with pore formation.

PMID- 18326670
TI  - Cultivation and ecosystem role of a marine roseobacter clade-affiliated cluster
      bacterium.
AB  - Isolation and cultivation are a crucial step in elucidating the physiology,
      biogeochemistry, and ecosystem role of microorganisms. Many abundant marine
      bacteria, including the widespread Roseobacter clade-affiliated (RCA) cluster
      group, have not been cultured with traditional methods. Using novel techniques of
      cocultivation with algal cultures, we have accomplished successful isolation and
      propagation of a strain of the RCA cluster. Our experiments revealed that, in
      addition to growing on alga-excreted organic matter, additions of washed
      bacterial cells led to significant biomass decrease of dinoflagellate cultures as
      measured by in vivo fluorescence. Bacterial filtrate did not adversely affect the
      algal cultures, suggesting attachment-mediated activity. Using an RCA cluster
      specific rRNA probe, we documented increasing attachment of these algicidal
      bacteria during a dinoflagellate bloom, with a maximum of 70% of the algal cells
      colonized just prior to bloom termination. Cross-correlation analyses between
      algal abundances and RCA bacterial colonization were statistically significant,
      in agreement with predator-prey models suggesting that RCA cluster bacteria
      caused algal bloom decline. Further investigation of molecular databases revealed
      that RCA cluster bacteria were numerically abundant during algal blooms sampled
      worldwide. Our findings suggest that the widespread RCA cluster bacteria may
      exert significant control over phytoplankton biomass and community structure in
      the oceans. We also suggest that coculture with phytoplankton may be a useful
      strategy to isolate and successfully grow previously uncultured but ecologically
      abundant marine heterotrophs.

PMID- 18326671
TI  - Taxonomic and strain-specific identification of the probiotic strain
      Lactobacillus rhamnosus 35 within the Lactobacillus casei group.
AB  - Lactobacilli are lactic acid bacteria that are widespread in the environment,
      including the human diet and gastrointestinal tract. Some Lactobacillus strains
      are regarded as probiotics because they exhibit beneficial health effects on
      their host. In this study, the long-used probiotic strain Lactobacillus rhamnosus
      35 was characterized at a molecular level and compared with seven reference
      strains from the Lactobacillus casei group. Analysis of rrn operon sequences
      confirmed that L. rhamnosus 35 indeed belongs to the L. rhamnosus species, and
      both temporal temperature gradient gel electrophoresis and ribotyping showed that
      it is closer to the probiotic strain L. rhamnosus ATCC 53103 (also known as L.
      rhamnosus GG) than to the species type strain. In addition, L. casei ATCC 334
      gathered in a coherent cluster with L. paracasei type strains, unlike L. casei
      ATCC 393, which was closer to L. zeae; this is evidence of the lack of
      relatedness between the two L. casei strains. Further characterization of the
      eight strains by pulsed-field gel electrophoresis repetitive DNA element-based
      PCR identified distinct patterns for each strain, whereas two isolates of L.
      rhamnosus 35 sampled 40 years apart could not be distinguished. By subtractive
      hybridization using the L. rhamnosus GG genome as a driver, we were able to
      isolate five L. rhamnosus 35-specific sequences, including two phage-related
      ones. The primer pairs designed to amplify these five regions allowed us to
      develop rapid and highly specific PCR-based identification methods for the
      probiotic strain L. rhamnosus 35.

PMID- 18326672
TI  - Molecular epidemiology of Bacillus anthracis: determining the correct origin.
AB  - We analyzed and compared strains of Bacillus anthracis isolated from husbandry
      and industrial anthrax cases in Switzerland between 1952 and 1981 with published
      data using multiple-locus variable-number tandem repeat analysis. Strains
      isolated from autochthonous cases of anthrax in cattle belong to genotype B2,
      together with strains from continental Europe, while human B. anthracis strains
      clustered with genotype A4. These strains could be traced back to outbreaks of
      human anthrax that occurred between 1978 and 1981 in a factory processing
      cashmere wool from the Indian subcontinent. We interpret the worldwide occurrence
      of B. anthracis strains of cluster A4 to be due to the extensive global trade of
      untreated cashmere wool during the last century.

PMID- 18326673
TI  - Feasibility of transferring fluorescent in situ hybridization probes to an 18S
      rRNA gene phylochip and mapping of signal intensities.
AB  - DNA microarray technology offers the possibility to analyze microbial communities
      without cultivation, thus benefiting biodiversity studies. We developed a DNA
      phylochip to assess phytoplankton diversity and transferred 18S rRNA probes from
      dot blot or fluorescent in situ hybridization (FISH) analyses to a microarray
      format. Similar studies with 16S rRNA probes have been done determined that in
      order to achieve a signal on the microarray, the 16S rRNA molecule had to be
      fragmented, or PCR amplicons had to be <150 bp in length to minimize the
      formation of a secondary structure in the molecule so that the probe could bind
      to the target site. We found different results with the 18S rRNA molecule. Four
      out of 12 FISH probes exhibited false-negative signals on the microarray; eight
      exhibited strong but variable signals using full-length 18S RNA molecules. A
      systematic investigation of the probe's accessibility to the 18S rRNA gene was
      made using Prymenisum parvum as the target. Fourteen additional probes identical
      to this target covered the regions not tested with existing FISH probes. Probes
      with a binding site in the first 900 bp of the gene generated positive signals.
      Six out of nine probes binding in the last 900 bp of the gene produced no signal.
      Our results suggest that although secondary structure affected probe binding, the
      effect is not the same for the 18S rRNA gene and the 16S rRNA gene. For the 16S
      rRNA gene, the secondary structure is stronger in the first half of the molecule,
      whereas in the 18S rRNA gene, the last half of the molecule is critical. Probe
      binding sites within 18S rRNA gene molecules are important for the probe design
      for DNA phylochips because signal intensity appears to be correlated with the
      secondary structure at the binding site in this molecule. If probes are designed
      from the first half of the 18S rRNA molecule, then full-length 18S rRNA molecules
      can be used in the hybridization on the chip, avoiding the fragmentation and the
      necessity for the short PCR amplicons that are associated with using the 16S rRNA
      molecule. Thus, the 18S rRNA molecule is a more attractive molecule for use in
      environmental studies where some level of quantification is desired. Target size
      was a minor problem, whereas for 16S rRNA molecules target size rather than probe
      site was important.

PMID- 18326674
TI  - Biochemical and molecular characterization of a novel type of Mutanase from
      Paenibacillus sp. strain RM1: identification of its mutan-binding domain,
      essential for degradation of Streptococcus mutans biofilms.
AB  - A novel type of mutanase (termed mutanase RM1) was isolated from Paenibacillus
      sp. strain RM1. The purified enzyme specifically hydrolyzed alpha-1,3-glucan
      (mutan) and effectively degraded biofilms formed by Streptococcus mutans, a major
      etiologic agent in the progression of dental caries, even following brief
      incubation. The nucleotide sequence of the gene for this protein contains a 3,873
      bp open reading frame encoding 1,291 amino acids with a calculated molecular mass
      of 135 kDa. The protein contains two major domains, the N-terminal domain (277
      residues) and the C-terminal domain (937 residues), separated by a characteristic
      sequence composed of proline and threonine repeats. The characterization of the
      recombinant proteins for each domain which were expressed in Escherichia coli
      demonstrated that the N-terminal domain had strong mutan-binding activity but no
      mutanase activity whereas the C-terminal domain was responsible for mutanase
      activity but had mutan-binding activity significantly lower than that of the
      intact protein. Importantly, the biofilm-degrading activity observed with the
      intact protein was not exhibited by either domain alone or in combination with
      the other. Therefore, these results indicate that the structural integrity of
      mutanase RM1 containing the N-terminal mutan-binding domain is required for the
      biofilm-degrading activity.

PMID- 18326675
TI  - Complete genome sequence of Nitrobacter hamburgensis X14 and comparative genomic
      analysis of species within the genus Nitrobacter.
AB  - The alphaproteobacterium Nitrobacter hamburgensis X14 is a gram-negative
      facultative chemolithoautotroph that conserves energy from the oxidation of
      nitrite to nitrate. Sequencing and analysis of the Nitrobacter hamburgensis X14
      genome revealed four replicons comprised of one chromosome (4.4 Mbp) and three
      plasmids (294, 188, and 121 kbp). Over 20% of the genome is composed of
      pseudogenes and paralogs. Whole-genome comparisons were conducted between N.
      hamburgensis and the finished and draft genome sequences of Nitrobacter
      winogradskyi and Nitrobacter sp. strain Nb-311A, respectively. Most of the
      plasmid-borne genes were unique to N. hamburgensis and encode a variety of
      functions (central metabolism, energy conservation, conjugation, and heavy metal
      resistance), yet approximately 21 kb of a approximately 28-kb "autotrophic"
      island on the largest plasmid was conserved in the chromosomes of Nitrobacter
      winogradskyi Nb-255 and Nitrobacter sp. strain Nb-311A. The N. hamburgensis
      chromosome also harbors many unique genes, including those for heme-copper
      oxidases, cytochrome b(561), and putative pathways for the catabolism of
      aromatic, organic, and one-carbon compounds, which help verify and extend its
      mixotrophic potential. A Nitrobacter "subcore" genome was also constructed by
      removing homologs found in strains of the closest evolutionary relatives,
      Bradyrhizobium japonicum and Rhodopseudomonas palustris. Among the Nitrobacter
      subcore inventory (116 genes), copies of genes or gene clusters for nitrite
      oxidoreductase (NXR), cytochromes associated with a dissimilatory nitrite
      reductase (NirK), PII-like regulators, and polysaccharide formation were
      identified. Many of the subcore genes have diverged significantly from, or have
      origins outside, the alphaproteobacterial lineage and may indicate some of the
      unique genetic requirements for nitrite oxidation in Nitrobacter.

PMID- 18326676
TI  - Development of a microbial time/temperature indicator prototype for monitoring
      the microbiological quality of chilled foods.
AB  - A time/temperature indicator (TTI) system based on the growth and metabolic
      activity of a Lactobacillus sakei strain was developed for monitoring food
      quality throughout the chilled-food chain. In the designed system, an
      irreversible color change of a chemical chromatic indicator (from red to yellow)
      progressively occurs due to the pH decline that results from microbial growth and
      metabolism in a selected medium. The relation of the TTI response (color change)
      to the growth and metabolic activity (glucose consumption, lactic acid
      production, pH decrease) of L. sakei was studied. In addition, the temperature
      dependence of the TTI kinetics was investigated isothermally in the range of 0 to
      16 degrees C and modeled with a system of differential equations. At all
      temperatures tested, the pH and color changes of the TTI system followed closely
      the growth of L. sakei, with the endpoint (the time at which a distinct visual
      color change to the final yellow was observed) of the TTI coinciding with a
      population level of 10(7) to 10(8) CFU/ml. The endpoint decreased from 27 days at
      0 degrees C to 2.5 days at 16 degrees C, yielding an activation energy of 97.7
      kJ/mol, which was very close to the activation energy of the L. sakei growth rate
      in the TTI substrate (103.2 kJ/mol). Furthermore, experiments conducted on the
      effect of the inoculum level showed a negative linear relationship between the
      level of L. sakei inoculated in the system medium and the endpoint of the TTI.
      For example, the endpoint at 8 degrees C ranged from 6 to 2 days for inoculum
      levels of 10(1) and 10(6) CFU/ml, respectively. This relationship allows the easy
      adjustment of the TTI endpoint at a certain temperature according to the shelf
      life of the food product of concern by using an appropriate inoculum level of L.
      sakei. The microbial TTI prototype developed in the present study could be used
      as an effective tool for monitoring shelf life during the distribution and
      storage of food products that are spoiled primarily by lactic acid bacteria or
      other bacteria exhibiting similar kinetic responses and spoilage potentials.
      Apart from the low cost, the main advantage of the proposed TTI is that its
      response closely matches the loss of the quality of a food product by simulating
      the microbial spoilage process in particular environments.

PMID- 18326677
TI  - Quantifying genes and transcripts to assess the in situ physiology of
      "Dehalococcoides" spp. in a trichloroethene-contaminated groundwater site.
AB  - Quantitative PCR (qPCR) was coupled with reverse transcription (RT) to analyze
      both gene copy numbers and transcripts of the 16S rRNA gene and three reductive
      dehalogenase (RDase) genes (tceA, vcrA, and bvcA) as biomarkers of
      "Dehalococcoides" spp. in the groundwater of a trichloroethene-dense nonaqueous
      phase liquid site at Fort Lewis, WA, that was sequentially subjected to
      biostimulation and bioaugmentation. Dehalococcoides cells carrying the tceA,
      vcrA, and bvcA genes were indigenous to the site. The sum of the three identified
      RDase gene copy numbers closely correlated to 16S rRNA gene copy numbers
      throughout the biostimulation and bioaugmentation activity, suggesting that these
      RDase genes represented the major Dehalococcoides metabolic functions at this
      site. Biomarker quantification revealed an overall increase of more than 3 orders
      of magnitude in the total Dehalococcoides population through the 1-year
      monitoring period (spanning biostimulation and bioaugmentation), and measurement
      of the respective RDase gene concentrations indicated different growth dynamics
      among Dehalococcoides cells. The Dehalococcoides cells containing the tceA gene
      consistently lagged behind other Dehalococcoides cells in population numbers and
      made up less than 5% of the total Dehalococcoides population, whereas the vcrA-
      and bvcA-containing cells represented the dominant fractions. Quantification of
      transcripts in groundwater samples verified that the 16S rRNA gene and the bvcA
      and vcrA genes were consistently highly expressed in all samples examined, while
      the tceA transcripts were detected inconsistently, suggesting a less active
      physiological state of the cells with this gene. The production of vinyl chloride
      and ethene toward the end of treatment supported the physiological activity of
      the bvcA- and vcrA-carrying cells. A clone library of the expressed RDase genes
      in field samples produced with degenerate primers revealed the expression of two
      putative RDase genes that were not previously monitored with RT-qPCR. The level
      of abundance of one of the putative RDase genes (FtL-RDase-1638) identified in
      the cDNA clone library tracked closely in field samples with abundance of the
      bvcA gene, suggesting that the FtL-RDase-1638 gene was likely colocated in
      genomes containing the bvcA gene. Overall, results from this study demonstrate
      that quantification of biomarker dynamics at field sites can provide useful
      information about the in situ physiology of Dehalococcoides strains and their
      associated activity.

PMID- 18326678
TI  - Functional nodFE genes are present in Sinorhizobium sp. strain MUS10, a symbiont
      of the tropical legume Sesbania rostrata.
AB  - We have cloned the nodFE operon from Sinorhizobium sp. strain MUS10. MUS10 NodF
      shows sequence homology to acyl carrier protein and enables an S. meliloti nodF
      mutant to effectively nodulate alfalfa. Our results demonstrate the occurrence of
      nodFE in a symbiont that nodulates a legume host not belonging to the galegoid
      group.

PMID- 18326679
TI  - Sheathless mutant of Cyanobacterium Gloeothece sp. strain PCC 6909 with increased
      capacity to remove copper ions from aqueous solutions.
AB  - The cyanobacterium Gloeothece sp. strain PCC 6909 and its sheathless mutant were
      tested for their abilities to remove copper ions from aqueous solutions, with the
      aim of defining the role of the various outermost polysaccharidic investments in
      the removal of the metal ions. Microscopy studies and chemical analyses revealed
      that, although the mutant does not possess a sheath, it releases large amounts of
      polysaccharidic material (released exocellular polysaccharides [RPS]) into the
      culture medium. The RPS of the wild type and the mutant are composed of the same
      11 sugars, although they are present in different amounts, and the RPS of the
      mutant possesses a larger amount of acidic sugars and a smaller amount of
      deoxysugars than the wild type. Unexpectedly, whole cultures of the mutant were
      more effective in the removal of the heavy metal than the wild type (46.3 +/- 3.1
      and 26.7 +/- 1.5 mg of Cu(2+) removed per g of dry weight, respectively).
      Moreover, we demonstrated that the contribution of the sheath to the metal
      removal capacity of the wild type is scarce and that the RPS of the mutant is
      more efficient in removing copper. This suggests that the metal ions are
      preferably bound to the cell wall and to RPS functional groups rather than to the
      sheath. Therefore, the increased copper binding efficiency observed with the
      sheathless mutant can be attributed to the release of a polysaccharide containing
      larger amounts and/or more accessible functional groups (e.g., carboxyl and amide
      groups).

PMID- 18326680
TI  - Mechanism for oxidation of high-molecular-weight substrates by a fungal versatile
      peroxidase, MnP2.
AB  - Unlike general peroxidases, Pleurotus ostreatus MnP2 was reported to have a
      unique property of direct oxidization of high-molecular-weight compounds, such as
      Poly R-478 and RNase A. To elucidate the mechanism for oxidation of polymeric
      substrates by MnP2, a series of mutant enzymes were produced by using a
      homologous gene expression system, and their reactivities were characterized. A
      mutant enzyme with an Ala substituting for an exposing Trp (W170A) drastically
      lost oxidation activity for veratryl alcohol (VA), Poly R-478, and RNase A,
      whereas the kinetic properties for Mn(2+) and H(2)O(2) were substantially
      unchanged. These results demonstrated that, in addition to VA, the high-molecular
      weight substrates are directly oxidized by MnP2 at W170. Moreover, in the mutants
      Q266F and V166/168L, amino acid substitution(s) around W170 resulted in a
      decreased activity only for the high-molecular-weight substrates. These results,
      along with the three-dimensional modeling of the mutants, suggested that the
      mutations caused a steric hindrance to access of the polymeric substrates to
      W170. Another mutant, R263N, contained a newly generated N glycosylation site and
      showed a higher molecular mass in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis analysis. Interestingly, the R263N mutant exhibited an increased
      reactivity with VA and high-molecular-weight substrates. The existence of an
      additional carbohydrate modification and the catalytic properties in this mutant
      are discussed. This is the first study of a direct mechanism for oxidation of
      high-molecular-weight substrates by a fungal peroxidase using a homologous gene
      expression system.

PMID- 18326681
TI  - Selenate-dependent anaerobic arsenite oxidation by a bacterium from Mono Lake,
      California.
AB  - Arsenate was produced when anoxic Mono Lake water samples were amended with
      arsenite and either selenate or nitrate. Arsenite oxidation did not occur in
      killed control samples or live samples with no added terminal electron acceptor.
      Potential rates of anaerobic arsenite oxidation with selenate were comparable to
      those with nitrate ( approximately 12 to 15 mumol.liter(-1) h(-1)). A pure
      culture capable of selenate-dependent anaerobic arsenite oxidation (strain ML
      SRAO) was isolated from Mono Lake water into a defined salts medium with
      selenate, arsenite, and yeast extract. This strain does not grow
      chemoautotrophically, but it catalyzes the oxidation of arsenite during growth on
      an organic carbon source with selenate. No arsenate was produced in pure cultures
      amended with arsenite and nitrate or oxygen, indicating that the process is
      selenate dependent. Experiments with washed cells in mineral medium demonstrated
      that the oxidation of arsenite is tightly coupled to the reduction of selenate.
      Strain ML-SRAO grows optimally on lactate with selenate or arsenate as the
      electron acceptor. The amino acid sequences deduced from the respiratory arsenate
      reductase gene (arrA) from strain ML-SRAO are highly similar (89 to 94%) to those
      from two previously isolated Mono Lake arsenate reducers. The 16S rRNA gene
      sequence of strain ML-SRAO places it within the Bacillus RNA group 6 of gram
      positive bacteria having low G+C content.

PMID- 18326682
TI  - New triplex real-time PCR assay for detection of Mycobacterium avium subsp.
      paratuberculosis in bovine feces.
AB  - In the present study, a robust TaqMan real-time PCR amplifying the F57 and the
      ISMav2 sequences of Mycobacterium avium subsp. paratuberculosis from bovine fecal
      samples was developed and validated. The validation was based on the
      recommendations of International Organization for Standardization protocols for
      PCR and real-time PCR methods. For specificity testing, 205 bacterial strains
      were selected, including 105 M. avium subsp. paratuberculosis strains of bovine,
      ovine, and human origin and 100 non-M. avium subsp. paratuberculosis strains.
      Diagnostic quality assurance was obtained by use of an internal amplification
      control. By investigating six TaqMan reagents from different suppliers, the 100%
      detection probability was assessed to be 0.1 picogram M. avium subsp.
      paratuberculosis DNA per PCR. The amplification efficiency was 98.2% for the
      single-copy gene F57 and 97.8% for the three-copy insertion sequence ISMav2. The
      analytical method was not limited due to instrument specificity. The triplex real
      time PCR allowed the reliable detection of M. avium subsp. paratuberculosis DNA
      using the ABI Prism 7000 sequence detection system, and the LightCycler 1.0.
      TaqMan(mgb) and locked nucleic acid fluorogenic probes were suitable for
      fluorescent signal detection. To improve the detection of M. avium subsp.
      paratuberculosis from bovine fecal samples, a more efficient DNA extraction
      method was developed, which offers the potential for automated sample processing.
      The 70% limit of detection was assessed to be 10(2) CFU per gram of spiked bovine
      feces. Comparative analysis of 108 naturally contaminated samples of unknown M.
      avium subsp. paratuberculosis status resulted in a relative accuracy of 98.9% and
      a sensitivity of 94.4% for fecal samples containing <10 CFU/g feces compared to
      the traditional culture method.

PMID- 18326683
TI  - The Type III secretion system of Xanthomonas fuscans subsp. fuscans is involved
      in the phyllosphere colonization process and in transmission to seeds of
      susceptible beans.
AB  - Understanding the survival, multiplication, and transmission to seeds of plant
      pathogenic bacteria is central to study their pathogenesis. We hypothesized that
      the type III secretion system (T3SS), encoded by hrp genes, could have a role in
      host colonization by plant pathogenic bacteria. The seed-borne pathogen
      Xanthomonas fuscans subsp. fuscans causes common bacterial blight of bean
      (Phaseolus vulgaris). Directed mutagenesis in strain CFBP4834-R of X. fuscans
      subsp. fuscans and bacterial population density monitoring on bean leaves showed
      that strains with mutations in the hrp regulatory genes, hrpG and hrpX, were
      impaired in their phyllospheric growth, as in the null interaction with
      Escherichia coli C600 and bean. In the compatible interaction, CFBP4834-R reached
      high phyllospheric population densities and was transmitted to seeds at high
      frequencies with high densities. Strains with mutations in structural hrp genes
      maintained the same constant epiphytic population densities (1 x 10(5) CFU g(-1)
      of fresh weight) as in the incompatible interaction with Xanthomonas campestris
      pv. campestris ATCC 33913 and the bean. Low frequencies of transmission to seeds
      and low bacterial concentrations were recorded for CFBP4834-R hrp mutants and for
      ATCC 33913, whereas E. coli C600 was not transmitted. Moreover, unlike the wild
      type strain, strains with mutations in hrp genes were not transmitted to seeds by
      vascular pathway. Transmission to seeds by floral structures remained possible
      for both. This study revealed the involvement of the X. fuscans subsp. fuscans
      T3SS in phyllospheric multiplication and systemic colonization of bean, leading
      to transmission to seeds. Our findings suggest a major contribution of hrp
      regulatory genes in host colonization processes.

PMID- 18326684
TI  - Highly selective and rapid arsenic removal by metabolically engineered
      Escherichia coli cells expressing Fucus vesiculosus metallothionein.
AB  - An arsenic-chelating metallothionein (fMT) from the arsenic-tolerant marine alga
      Fucus vesiculosus was expressed in Escherichia coli, resulting in 30- and 26-fold
      higher As(III) and As(V) binding, respectively. Coexpression of the As(III)
      specific transporter GlpF with fMT further improved arsenic accumulation and
      offered high selectivity toward As. Resting E. coli cells coexpressing fMT and
      GlpF completely removed trace amounts (35 ppb) of As(III) within 20 min,
      providing a promising technology for compliance with the As limit of 10 ppb newly
      recommended by the U.S. EPA.

PMID- 18326685
TI  - Analysis of neurotoxin cluster genes in Clostridium botulinum strains producing
      botulinum neurotoxin serotype A subtypes.
AB  - Neurotoxin cluster gene sequences and arrangements were elucidated for strains of
      Clostridium botulinum encoding botulinum neurotoxin (BoNT) subtypes A3, A4, and a
      unique A1-producing strain (HA(-) Orfx(+) A1). These sequences were compared to
      the known neurotoxin cluster sequences of C. botulinum strains that produce
      BoNT/A1 and BoNT/A2 and possess either a hemagglutinin (HA) or an Orfx cluster,
      respectively. The A3 and HA(-) Orfx(+) A1 strains demonstrated a neurotoxin
      cluster arrangement similar to that found in A2. The A4 strain analyzed possessed
      two sets of neurotoxin clusters that were similar to what has been found in the
      A(B) strains: an HA cluster associated with the BoNT/B gene and an Orfx cluster
      associated with the BoNT/A4 gene. The nucleotide and amino acid sequences of the
      neurotoxin cluster-specific genes were determined for each neurotoxin cluster and
      compared among strains. Additionally, the ntnh gene of each strain was compared
      on both the nucleotide and amino acid levels. The degree of similarity of the
      sequences of the ntnh genes and corresponding amino acid sequences correlated
      with the neurotoxin cluster type to which the ntnh gene was assigned.

PMID- 18326686
TI  - Comparison of BGM and PLC/PRC/5 cell lines for total culturable viral assay of
      treated sewage.
AB  - The objective of this study was to compare PLC/PRF/5 and BGM cell lines for use
      in a total culturable viral assay (TCVA) of treated sewage effluents. Samples
      were collected before and after chlorination from an activated sludge wastewater
      treatment plant and from the effluent of a high-rate enhanced flocculation
      system, followed by UV light disinfection. Cell monolayers were observed for
      cytopathic effect (CPE) after two passages of 14 days each. Monolayers exhibiting
      viral CPE were tested for the presence of adenoviruses and enteroviruses by PCR
      or reverse transcription-PCR. Eight percent of the samples exhibited CPE on BGM
      cells, and 57% showed CPE on PLC/PRF/5 cells. Only enteroviruses were detected on
      the BGM cells, while 30% and 52% of the samples were positive for enteroviruses
      and adenoviruses, respectively, on the PLC/PRF/5 cells. Thirty percent of the
      samples were positive for both adenoviruses and enteroviruses in chlorinated
      activated sludge effluent. Thirty percent of the samples were positive for
      adenoviruses in the UV treatment effluent, but no enteroviruses were detected. In
      conclusion, the PLC/PRF/5 cells were more susceptible than BGM cells to viruses
      found in treated sewage. The use of BGM cells for TCVA may underestimate viral
      concentration in sewage effluent samples. The PLC/PRF/5 cells were more
      susceptible to adenoviruses, which is important in the evaluation of UV
      disinfection systems because adenoviruses are highly resistant to UV
      inactivation.

PMID- 18326688
TI  - Mapping translocation breakpoints by next-generation sequencing.
AB  - Balanced chromosome rearrangements (BCRs) can cause genetic diseases by
      disrupting or inactivating specific genes, and the characterization of
      breakpoints in disease-associated BCRs has been instrumental in the molecular
      elucidation of a wide variety of genetic disorders. However, mapping chromosome
      breakpoints using traditional methods, such as in situ hybridization with
      fluorescent dye-labeled bacterial artificial chromosome clones (BAC-FISH), is
      rather laborious and time-consuming. In addition, the resolution of BAC-FISH is
      often insufficient to unequivocally identify the disrupted gene. To overcome
      these limitations, we have performed shotgun sequencing of flow-sorted derivative
      chromosomes using "next-generation" (Illumina/Solexa) multiplex sequencing-by
      synthesis technology. As shown here for three different disease-associated BCRs,
      the coverage attained by this platform is sufficient to bridge the breakpoints by
      PCR amplification, and this procedure allows the determination of their exact
      nucleotide positions within a few weeks. Its implementation will greatly
      facilitate large-scale breakpoint mapping and gene finding in patients with
      disease-associated balanced translocations.

PMID- 18326689
TI  - Aqueous humor levels of vascular endothelial growth factor in retinitis
      pigmentosa.
AB  - PURPOSE: To determine the level of vascular endothelial growth factor A (VEGF-A)
      in aqueous humors of patients with retinitis pigmentosa (RP). METHODS: A
      prospective, comparative control study. Aqueous humor was collected from 16 eyes
      of 16 patients with RP. The level of VEGF-A was determined with a commercially
      available enzyme-linked immunosorbent assay kit. The control group comprised 16
      aqueous samples from 16 patients about to undergo cataract surgery and without
      any other ocular or systemic diseases. RESULTS: The concentration of VEGF-A in
      aqueous humor was markedly lower in patients with RP than in control subjects
      (Mann-Whitney U test, P < 0.001). The level of VEGF-A was 94.9 +/- 99.8 (mean +/-
      SD) pg/mL in eyes with RP and 336.5 +/- 116.8 pg/mL in the eyes of the control
      group. CONCLUSIONS: In patients with RP, the concentration of VEGF-A in aqueous
      humors is lower than in non-RP subjects. The lack of angiogenic actions
      attributed to VEGF-A may explain some of the clinical manifestations of this
      disease, such as narrowing and fibrotic degeneration of retinal blood vessels.

PMID- 18326690
TI  - Targeting hypoxia, a novel treatment for advanced retinoblastoma.
AB  - PURPOSE: The purpose of this study was to evaluate the presence and extent of
      hypoxia in murine retinoblastoma tumors and the feasibility of targeting hypoxic
      cells as a novel therapeutic strategy. METHODS: Hypoxic and vascular areas in
      LH(BETA)T(AG) mouse retinal tumors were measured using immunohistochemistry. The
      glycolytic inhibitor 2-deoxy-d-glucose (2-DG) was used to test the efficacy of
      targeting hypoxic cells in retinoblastoma. Sixteen-week-old LH(BETA)T(AG) mice
      received injections of saline, carboplatin (31.25 microg/20 microL), 2-DG (500
      mg/kg), and carboplatin (31.25 microg/20 microL) + 2-DG (500 mg/kg). Carboplatin
      was administered through biweekly subconjunctival injections to right eyes only
      for 3 weeks. 2-DG was administered through intraperitoneal injection three times
      a week for 5 weeks. Saline was administered using both methods. Eyes were
      enucleated at 21 weeks of age and examined for residual tumor. RESULTS: Hypoxic
      regions were observed in tumors larger than 3.28 mm(2). When 2-DG was combined
      with carboplatin, a marked decrease in tumor burden was observed that was
      significantly more pronounced than when either agent was given alone. The hypoxic
      tumor cell population as measured by pimonidazole was markedly reduced by
      carboplatin + 2-DG (P < 0.01) and by 2-DG alone (P < 0.01), but not by
      carboplatin alone, indicating that 2-DG effectively killed hypoxic retinoblastoma
      cells in vivo. CONCLUSIONS: Treatment with glycolytic inhibitors as adjuvants to
      chemotherapy has the potential to increase the efficacy of chemotherapy in
      advanced retinoblastoma. This approach may have benefits for children with this
      disease and should be further investigated.

PMID- 18326692
TI  - Isolated ocular disease is associated with decreased mucolipin-1 channel
      conductance.
AB  - PURPOSE: To evaluate a 15-year-old boy with MLIV (mucolipidosis type IV) and
      clinical abnormalities restricted to the eye who also had achlorhydria with
      elevated blood gastrin levels. METHODS: In addition to a detailed neuro
      ophthalmic and electrophysiological assessment, his mutant mucolipin-1 was
      experimentally expressed in liposomes and its channel properties studied in
      vitro. RESULTS: The patient was a compound heterzygote for c.920delT and
      c.1615delG. Detailed neuro-ophthalmic examination including electroretinography
      showed him to have a typical retinal dystrophy predominantly affecting rod and
      bipolar cell function. In vitro expression of MCOLN1 in liposomes showed that the
      c.1615delG mutated channel had significantly reduced conductance compared with
      wild-type mucolipin-1, whereas the inhibitory effect of low pH and amiloride
      remained intact. CONCLUSIONS: These findings suggest that reduced channel
      conductance is relatively well tolerated by the brain during development, whereas
      retinal cells and stomach parietal cells require normal protein function. MLIV
      should be considered in patients with retinal dystrophy of unknown cause and
      screened for using blood gastrin levels.

PMID- 18326691
TI  - Ceruloplasmin/hephaestin knockout mice model morphologic and molecular features
      of AMD.
AB  - PURPOSE: Iron is an essential element in human metabolism but also is a potent
      generator of oxidative damage with levels that increase with age. Several studies
      suggest that iron accumulation may be a factor in age-related macular
      degeneration (AMD). In prior studies, both iron overload and features of AMD were
      identified in mice deficient in the ferroxidase ceruloplasmin (Cp) and its
      homologue hephaestin (Heph) (double knockout, DKO). In this study, the location
      and timing of iron accumulation, the rate and reproducibility of retinal
      degeneration, and the roles of oxidative stress and complement activation were
      determined. METHODS: Morphologic analysis and histochemical iron detection by
      Perls' staining was performed on retina sections from DKO and control mice.
      Immunofluorescence and immunohistochemistry were performed with antibodies
      detecting activated complement factor C3, transferrin receptor, L-ferritin, and
      macrophages. Tissue iron levels were measured by atomic absorption
      spectrophotometry. Isoprostane F2alpha-VI, a specific marker of oxidative stress,
      was quantified in the tissue by gas chromatography/mass spectrometry. RESULTS:
      DKOs exhibited highly reproducible age-dependent iron overload, which plateaued
      at 6 months of age, with subsequent progressive retinal degeneration continuing
      to at least 12 months. The degeneration shared some features of AMD, including
      RPE hypertrophy and hyperplasia, photoreceptor degeneration, subretinal
      neovascularization, RPE lipofuscin accumulation, oxidative stress, and complement
      activation. CONCLUSIONS: DKOs have age-dependent iron accumulation followed by
      retinal degeneration modeling some of the morphologic and molecular features of
      AMD. Therefore, these mice are a good platform on which to test therapeutic
      agents for AMD, such as antioxidants, iron chelators, and antiangiogenic agents.

PMID- 18326693
TI  - Minus-lens-stimulated accommodative amplitude decreases sigmoidally with age: a
      study of objectively measured accommodative amplitudes from age 3.
AB  - PURPOSE: Guidelines for predicting accommodative amplitude by age are often based
      on subjective push-up test data that overestimate the accommodative response.
      Studies in which objective measurements were used have defined expected
      amplitudes for adults, but expected amplitudes for children remain unknown. In
      this study, objective methods were used to measure accommodative amplitude in a
      wide age range of individuals, to define the relationship of amplitude and age
      from age 3. METHODS: Accommodative responses were measured in 140 subjects aged 3
      to 40 years. Measurements were taken with the Grand Seiko autorefractor (RyuSyo
      Industrial Co., Ltd., Kagawa, Japan) as the subjects viewed a high-contrast
      target at 33 cm through minus lenses of increasing power until the responses
      showed no further increase in accommodation. RESULTS: The maximum accommodative
      amplitude of each subject was plotted by age, and a curvilinear function fit to
      the data: y = 7.33 - 0.0035(age - 3)(2) (P < 0.001). Tangent analysis of the fit
      indicated that the accommodative amplitude remained relatively stable until age
      20. Data from this study were then pooled with objective amplitudes from previous
      studies of adults up to age 70. A sigmoidal function was fit to the data: y =
      7.083/(1 + e([0.2031(age-36.2)-0.6109])) (P < 0.001). The sigmoidal function
      indicated relatively stable amplitudes below age 20 years, a rapid linear decline
      between 20 and 50 years, and a taper to 0 beyond 50 years. CONCLUSIONS: These
      data indicate that accommodative amplitude decreases in a curvilinear manner from
      3 to 40 years. When combined with data from previous studies, a sigmoidal
      function describes the overall trend throughout life with the biggest decrease
      occurring between 20 and 50 years.

PMID- 18326694
TI  - Cataracts are caused by alterations of a critical N-terminal positive charge in
      connexin50.
AB  - PURPOSE: To elucidate the basis of the autosomal dominant congenital nuclear
      cataracts caused by the connexin50 mutant, CX50R23T, by determining its cellular
      distribution and functional behavior and the consequences of substituting other
      amino acids for arginine-23. METHODS: Connexin50 (CX50) mutants were generated by
      PCR and transfected into HeLa or N2a cells. Expressed CX50 protein was detected
      by immunoblot analysis and localized by immunofluorescence. Intercellular
      communication was assessed by microinjection of neurobiotin or by double whole
      cell patch-clamp recording. RESULTS: HeLa cells stably transfected with CX50R23T
      or wild-type CX50 produced immunoreactive CX50 bands of identical electrophoretic
      mobility. Whereas HeLa cells stably expressing CX50 contained abundant gap
      junction plaques, CX50R23T localized predominantly in the cytoplasm. HeLa cells
      expressing wild-type CX50 showed large gap junctional conductances and extensive
      transfer of neurobiotin, but those expressing CX50R23T did not show significant
      intercellular communication by either assay. Moreover, CX50R23T inhibited the
      function of coexpressed wild-type CX50. Three CX50R23 substitution mutants
      (CX50R23K, CX50R23L, and CX50R23W) formed gap junction plaques, whereas two
      mutant substitutions with negatively charged residues (CX50R23D, CX50R23E) did
      not form detectable plaques. Only the mutant with a positive charge substitution
      (CX50R23K) allowed neurobiotin transfer at levels similar to those of wild-type
      CX50; none of the other mutants induced transfer. CONCLUSIONS: These results
      suggest that replacement of amino acid 23 in CX50 by any residue that is not
      positively charged would lead to cataract formation.

PMID- 18326695
TI  - A primate model of nonarteritic anterior ischemic optic neuropathy.
AB  - PURPOSE: Nonarteritic anterior ischemic optic neuropathy (NAION) is an optic
      nerve (ON) stroke and a leading cause of sudden ON-related vision loss. A primate
      (p)NAION model is crucial to further understanding of the clinical disorder and
      can provide information regarding the pathophysiology of other central nervous
      system (CNS) ischemic axonopathies. In the current study, a primate model of
      NAION was developed, and short-and long-term responses to this condition were
      characterized. METHODS: pNAION was induced with a novel photoembolic mechanism.
      Short-and long-term responses were evaluated by minimally invasive testing
      (electrophysiology, fundus photography, indocyanine green and fluorescein
      angiography, and magnetic resonance imaging) and compared with histologic and
      immunohistochemical findings. RESULTS: Optic disc edema, similar to that observed
      in cases of human NAION was seen 1 day after induction, with subsequent
      resolution associated with the development of optic disc pallor. Magnetic
      resonance imaging (MRI) performed 3 months after induction revealed changes
      consistent with ON atrophy. Electrophysiological studies and vascular imaging
      suggest an ON-limited infarct with subsequent axonal degeneration and selective
      neuronal loss similar to that seen in human NAION. ON inflammation was evident 2
      months after induction at the site of the lesion and at distant sites, suggesting
      that inflammation-associated axonal remodeling continues for an extended period
      after ON infarct. CONCLUSIONS: pNAION resembles human NAION in many respects,
      with optic disc edema followed by loss of cells in the retinal ganglion cell
      (RGC) layer and ON remodeling. This model should be useful for evaluating
      neuroprotective and other treatment strategies for human NAION as well as for
      other ischemic processes that primarily affect CNS white-matter tracts.

PMID- 18326696
TI  - Glaucoma and on-road driving performance.
AB  - PURPOSE: To investigate the on-road driving performance of patients with
      glaucoma. METHODS: The sample comprised 20 patients with glaucoma and 20 subjects
      with normal vision, all licensed drivers, matched for age and sex. Driving
      performance was tested over a 10-km route incorporating 55 standardized maneuvers
      and skills through residential and business districts of Halifax, Nova Scotia,
      Canada. Testing was conducted by a professional driving instructor and assessed
      by an occupational therapist certified in driver rehabilitation, masked to
      participant group membership and level of vision. Main outcome measures were
      total number of satisfactory maneuvers and skills, overall rating, and incidence
      of at-fault critical interventions (application of the dual brake and/or steering
      override by the driving instructor to prevent a potentially unsafe maneuver).
      Measures of visual function included visual acuity, contrast sensitivity, and
      visual fields (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA;
      mean deviation [MD] and binocular Esterman points). RESULTS: There was no
      significant difference between patients with glaucoma (mean MD = -1.7 dB [SD 2.2]
      and -6.5 dB [SD 4.9], better and worse eyes, respectively) and control subjects
      in total satisfactory maneuvers and skills (P = 0.65), or overall rating (P =
      0.60). However, 12 (60%) patients with glaucoma had one or more at-fault critical
      interventions, compared with 4 (20%) control subjects (odds ratio = 6.00, 95% CI,
      1.46-24.69; higher still after adjustment for age, sex, medications and driving
      exposure), the predominant reason being failure to see and yield to a pedestrian.
      In the glaucoma group, worse-eye MD was associated with the overall rating of
      driving (r = 0.66, P = 0.002). CONCLUSIONS: This sample of patients with glaucoma
      with slight to moderate visual field impairment performed many real-world driving
      maneuvers safely. However, they were six times as likely as subjects with normal
      vision to have a driving instructor intervene for reasons suggesting difficulty
      with detection of peripheral obstacles and hazards and reaction to unexpected
      events.

PMID- 18326697
TI  - Human RPE melanosomes protect from photosensitized and iron-mediated oxidation
      but become pro-oxidant in the presence of iron upon photodegradation.
AB  - PURPOSE: To determine the effects of human retinal pigment epithelial (RPE) cell
      pigment granules on photosensitized and iron ion-mediated oxidation and the
      effect of the photodegradation of melanosomes on their antioxidant properties.
      METHODS: RPE cells were isolated from human and bovine eyes; pigmented and
      nonpigmented bovine retinal pigment epithelia were isolated separately.
      Melanosomes, melanolipofuscin, and lipofuscin granules were isolated from human
      RPE donors older than 60. Melanosomes were photodegraded by exposure to blue
      light. Oxidation of RPE cells or of linoleate was induced by iron/ascorbate in
      the presence and absence of pigment granules. The photosensitized oxidation of
      histidine was induced by blue light irradiation of cationic porphyrin. The
      progress of oxidation was monitored by electron spin resonance oximetry. RESULTS:
      Iron/ascorbate induced rapid oxidation in suspensions of nonpigmented bovine RPE
      cells. The rates of oxidation were diminished approximately four times in
      suspensions of pigmented bovine RPE cells. Adding bovine melanosomes or synthetic
      melanin to nonpigmented bovine RPE cells resulted in a concentration-dependent
      decrease in the rate of oxidation to levels similar to those of pigmented bovine
      retinal pigment epithelium. Human melanosomes exerted a concentration-dependent
      inhibitory effect on photosensitized and iron-mediated oxidation.
      Photodegradation of human melanosomes led to loss of the inhibitory effect on
      iron-mediated oxidation, whereas their ability to inhibit photosensitized
      oxidation was enhanced. CONCLUSIONS: Human melanosomes act as effective
      antioxidants by preventing iron ion-induced oxidation. Photodegradation of
      melanosomes results in the loss of these antioxidant properties while it
      preserves their ability to deactivate cationic photosensitizers.

PMID- 18326698
TI  - Automated assessment of the optic nerve head on stereo disc photographs.
AB  - PURPOSE: To develop automated software for optic nerve head (ONH) quantitative
      assessment from stereoscopic disc photographs and to evaluate its performance in
      comparison with human expert assessment. METHODS: A fully automated system,
      including three-dimensional ONH modeling, disc margin detection, cup margin
      detection, and calculation of stereometric ONH parameters, was developed and
      tested. One eye each from 54 subjects (23 healthy, 17 suspected glaucoma, and 14
      glaucoma) was enrolled. The majority opinion of three experts defined disc and
      cup margins on the disc photographs was used for comparison. Seven ONH
      parameters, disc area, rim area, rim volume, cup area, cup volume, cup-to-disc
      (C/D) area ratio, and vertical C/D ratio, were computed based on both machine-
      and expert-defined margins and compared between the methods. RESULTS: All
      automated ONH measurements showed good correlation with the expert defined
      margins (Pearson r = 0.90, disc area; 0.56, rim area; 0.78, rim volume; 0.88, cup
      area; 0.93, cup volume; 0.69, C/D area ratio; and 0.67, vertical C/D ratio; all P
      <or= 0.0001). No statistically significant difference was found in the glaucoma
      discriminating ability of all seven ONH parameters (P >or= 0.21). The mean or
      median of automatically defined disc and cup areas was significantly higher than
      the subjective assessment (disc area P = 0.0001, t-test; cup area P = 0.036,
      Wilcoxon signed ranks test), although they had high correlation coefficients. The
      software failed to detect the disc margin for all the disc photographs with
      peripapillary atrophy. CONCLUSIONS: The automated ONH analysis method provides an
      objective and quantitative ONH evaluation using widely available stereo disc
      photographs.

PMID- 18326699
TI  - Effect of repeated IOP challenge on rat retinal function.
AB  - PURPOSE: To characterize the effect of repeated brief intraocular pressure (IOP)
      elevations and the effect of IOP fluctuation on retinal function. METHODS: The
      effects of one, two, and four episodes (70 mm Hg, 15 minutes) are compared by
      defining the time course of functional recovery after insults. The effect of IOP
      variation is considered by comparing a constant with a varying insult, keeping a
      common IOP-time integral (one 60-minute vs. two 30-minute vs. four 15-minute
      insults; 70 mm Hg). IOP elevation is induced by anterior chamber cannulation in
      anesthetized, dark-adapted rats (n = 5-7 per group). Electroretinograms are
      recorded every 6 minutes throughout each event. Recovery time course is modeled
      using a logistic function, and time for 50% recovery is compared by nonparametric
      bootstrap. RESULTS: Electroretinographic recovery becomes progressively slower
      with more IOP episodes for bipolar cell and ganglion cell response (P < 0.05) but
      not for photoreceptor response (P > 0.05). With regard to IOP variation, bipolar
      cell recovery after four 15-minute insults is faster than it is after two 30
      minute insults (P < 0.05), which is faster than after one 60-minute insult (P <
      0.05). Ganglion cell recovery after varying (four 15-minute and two 30-minute)
      insults is faster than after a constant (one 60-minute) insult (P < 0.05). This
      improved recovery with varying IOP challenge is greater for bipolar cell than for
      ganglion cell responses (P < 0.05). CONCLUSIONS: Repeated IOP insults lead to
      cumulative dysfunction in the inner retina. For the conditions used in this
      study, IOP variation per se is not detrimental but appears to be beneficial.

PMID- 18326700
TI  - Macular pigment and age-related macular degeneration: longitudinal data and
      better techniques of measurement are needed.

PMID- 18326702
TI  - Ocular torsion reveals the mechanisms of cyclovertical strabismus: the Weisenfeld
      lecture.

PMID- 18326703
TI  - Astigmatism associated with experimentally induced myopia or hyperopia in
      chickens.
AB  - PURPOSE: Astigmatism is a very common refractive error in humans, but its
      etiology is poorly understood. The primary purpose of this study was to determine
      whether alterations in visual experience would result in astigmatism in chicks.
      METHODS: Longitudinal and cross-sectional data were obtained from chicks that
      were raised undergoing four different visual manipulations known to alter axial
      eye growth: form deprivation by translucent occluders, spherical defocus by -10-
      or +10-D lenses, and constant light. The visual manipulations began at 5 days of
      age and continued for a week. Age-matched groups raised without any treatment or
      with Velcro rings or plano lenses served as control groups. Refractions in all
      birds were measured with a Hartinger refractometer, and infrared photokeratometry
      was performed in a subset of birds at the end of the treatment period. RESULTS:
      In control birds, natural astigmatism decreased in magnitude over the 7-day
      treatment period. In contrast, birds treated with visual manipulations developed
      significant amounts of astigmatism throughout the treatment period. At the end of
      the 7-day treatment period, whereas only 8.6% of the control chicks had
      refractive astigmatism >1 D, the percentage of treated birds that had astigmatism
      >1 D in each treatment group ranged from 66.7% to 100%. The astigmatism in the
      treated eyes was predominantly against-the-rule, corneal in nature, and
      correlated significantly with spherical ametropia of the principal meridians.
      CONCLUSIONS: Visual manipulations known to induce axial ametropia also promote
      the genesis of astigmatism in chickens. The characteristics of astigmatism
      associated with spherical myopia or hyperopia in chicks is similar to those
      reported in humans in many respects, supporting the hypothesis that vision
      dependent changes in eye growth may contribute to the astigmatism commonly found
      in humans.

PMID- 18326704
TI  - A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian
      patients.
AB  - PURPOSE: Autosomal recessive ocular albinism (AROA) is a group of genetic
      disorders in which reduced pigmentation of the eye is associated with decreased
      visual acuity, nystagmus, strabismus, and photophobia, although pigmentation of
      skin and hair is relatively normal. Previous studies have shown that AROA in some
      cases constitutes a clinically mild presentation of oculocutaneous albinism
      (OCA), due to mutations in either the TYR (OCA1) or OCA2 (P) genes. The purpose
      of this study was to characterize the relative prevalence of different genetic
      forms of AROA, and to characterize a sample repertoire of gene mutations in a
      large series of Caucasian patients with AROA. METHODS: Thirty-six unrelated
      Caucasian patients carrying the clinical diagnosis of AROA were studied by DNA
      sequence analysis of the four classic OCA genes: TYR, OCA2 (P), TYRP1, and
      SLC45A2 (MATP), as appropriate. In all patients with no apparent pathologic
      mutations in these genes, DNA sequence analysis was performed of a candidate OCA
      gene, SILV, and the two genes most often involved in Hermansky-Pudlak syndrome,
      HPS1 and HPS4, the most frequent syndromic form of OCA. RESULTS: TYR gene
      mutations were identified in 20 (56%) patients, OCA2 mutations in 3 (8%),
      mutations in both TYR and OCA2 in 2 (6%), and possible TYRP1 mutations in 2 (6%).
      In at least nine patients, no mutations were found in any of the genes studied.
      Almost all patients with OCA1-related AROA were compound heterozygous for severe
      OCA1 mutant alleles and the common R402Q variant. CONCLUSIONS: Most patients with
      AROA represent phenotypically mild variants of OCA, well over half of which is
      OCA1.

PMID- 18326705
TI  - The effect of parental history of myopia on children's eye size and growth:
      results of a longitudinal study.
AB  - PURPOSE: To evaluate the effect of parental myopia on eye size and growth in
      Chinese children. METHODS: A school-based, cross-sectional survey was performed
      in Chinese children 5 to 16 years of age. A longitudinal cohort study was
      conducted 1 year later. The effects of parental myopia, parental education level,
      and near work performed by the child on the refractive error and ocular biometry
      of the child were assessed. RESULTS: There were 7560 children enrolled in the
      initial study (response rate: 76.3%). One year later, 4468 children (response
      rate: 75.9%) in the original cohort (with the exception of those who had
      completed primary schooling) were evaluated, to determine eye growth. Although
      children with a stronger parental history of myopia tended to be less hyperopic
      before the onset of myopia (spherical equivalent refraction [SER] = 0.43 D, 0.67
      D, and 0.68 D in children with two, one, and no myopic parents respectively; P =
      0.007), the axial lengths did not follow the same pattern (axial length [AL] =
      23.11, 23.07, and 23.15 mm; P = 0.429). Eye growth and myopic shift in refraction
      occurred more rapidly among children with a stronger parental history of myopia
      (annual AL growth/myopia progression = 0.37 mm/-0.22 D, 0.26 mm/-0.07 D, and 0.20
      mm/-0.02 D in children with two, one, and no myopic parents, respectively; P <
      0.001). CONCLUSIONS: Ocular biometric data in Chinese children suggest that
      parental history of myopia influences the growth rate of the eye, rather than its
      size before the onset of myopia, as previously reported in Caucasian children.
      Further longitudinal studies involving children of different ethnicities are
      warranted.

PMID- 18326706
TI  - Prevalence and causes of functional low vision in school-age children: results
      from standardized population surveys in Asia, Africa, and Latin America.
AB  - PURPOSE: Data on the prevalence and causes of functional low vision (FLV) in
      adults and children are lacking but are important for planning low-vision
      services. This study was conducted to determine the prevalence and causes of FLV
      among children recruited in eight population-based prevalence surveys of visual
      impairment and refractive error from six countries (India [2 locations]; China [2
      locations]; Malaysia, Chile, Nepal, and South Africa). METHODS: Using the same
      protocol, 4082 to 6527 children aged 5 (or 7) to 15 years were examined at each
      site. Uncorrected and presenting visual acuities were successfully measured with
      retroilluminated logMAR tumbling-E charts in 3997 to 5949 children; cycloplegic
      autorefraction was performed and best corrected acuities assessed. All children
      were examined by an ophthalmologist and a cause of visual loss assigned to eyes
      with uncorrected acuity < or =6/12. The prevalence of FLV was determined overall
      and by site; associations with gender, age, parental education and urban/rural
      location were assessed with logistic regression. RESULTS: The prevalence of FLV
      ranged from 0.65 to 2.75 in 1000 children, with wide confidence intervals. The
      overall prevalence was 1.52 in 1000 children (95% CI 1.16-1.95). FLV was
      significantly associated with age (odds ratio [OR] 1.13 for each year, P = 0.01),
      and parental education was protective (OR 0.75 for each of five levels of
      education, P = 0.017). Retinal lesions and amblyopia were the commonest causes.
      CONCLUSIONS: More studies are needed to determine the prevalence and causes of
      FLV in children so that services can be planned that promote independence,
      improve quality of life, and increase access to education.

PMID- 18326707
TI  - Myopia and personality: the genes in myopia (GEM) personality study.
AB  - PURPOSE: A long-held view among the medical and broader community is that people
      who are short-sighted (myopic persons) have distinctive personality
      characteristics such as introversion and conscientiousness. However, existing
      research on this question is flawed, and its findings are inconsistent. The
      authors therefore aimed to determine whether myopia and personality are
      associated. METHODS: The authors examined twins recruited through the Australian
      Twin Registry and a clinical-based family sample through a proband from a
      Melbourne Excimer Laser Clinic. There was no relation between family members and
      twins recruited in our study. Each individual underwent a full eye examination,
      completed a standard medical and general questionnaire, and was administered a
      five-factor model International Personality Item Pool (IPIP) inventory (Openness,
      Conscientiousness, Extroversion, Agreeableness, Neuroticism). Myopia was defined
      as worse than or equal to -0.50 (DS) spherical equivalent in the eye with the
      least refractive error. RESULTS: Data from 633 individual twins aged 18 to 83
      years (mean, 53.04 years) and 278 family members aged 11 to 90 years (mean, 49.84
      years) were analyzed. Prevalence of myopia was 35.7% for twins and 47.6% for
      family members. Mean spherical equivalent was +0.13 DS (95% CI, +/-0.16) for
      twins and -1.13 DS (95% CI, +/-0.25) for family members. Correlation and
      regression results for personality for both sample cohorts after multivariate
      analysis did not support the view that myopic persons are introverted or
      conscientious; however, there was a significant but small association between
      myopia and Agreeableness (r = 0.08, P < 0.05). In multivariate analysis with age,
      sex, education, and the five personality factors entered as predictors, Openness
      was the only significant personality predictor of myopia in both samples.
      CONCLUSIONS: This is the first multivariate study to assess links between
      personality and myopia using the IPIP. The long-held view that myopic persons are
      introverted and conscientious may reflect intelligence-related stereotypes rather
      than real correlations. Furthermore, the predictive characteristic of intellect,
      subsumed in Openness, appeared to be representative of a previously reported link
      between intellective abilities (IQ) and myopia rather than personality and
      myopia.

PMID- 18326708
TI  - Prevalence and causes of functional low vision and implications for services: the
      Pakistan National Blindness and Visual Impairment Survey.
AB  - PURPOSE: To determine the prevalence and causes of functional low vision (FLV)
      and total blindness and to estimate the assessment needs for low-vision services
      in Pakistan. METHODS: Multistage, cluster random sampling was used to select a
      nationally representative sample of adults (age, > or =30 years). Participants
      underwent visual acuity measurement and detailed ophthalmic examination.
      Functional low vision was defined as a corrected visual acuity in the better eye
      of less than 6/18 to more than no perception of light (NPL) in individuals with
      untreatable causes of visual loss. Total blindness was defined as NPL in both
      eyes. Needs assessments were categorized into three groups: optical services,
      nonoptical/environmental interventions, and rehabilitation. RESULTS: A sample of
      16,507 adults (95.3% response rate) was examined. The standardized prevalence of
      FLV and total blindness were 1.7% (95% CI: 1.5%-1.9%) and 0.2% (95% CI: 0.1%
      0.2%), respectively. More than 90% of those with FLV were illiterate and 35.3%
      were of working age (i.e., <60 years). An estimated 727,000 (586,000-891,000)
      adults in Pakistan had FLV. Retinal conditions were the commonest cause in urban
      populations (39.8% vs. 26.5% rural) compared with corneal opacity in rural areas
      (38.0% vs. 25.5% urban). It was estimated that 565,000 adults require assessment
      for optical services, 735,000 for nonoptical interventions, and 424,000 for
      rehabilitation. CONCLUSIONS: As VISION 2020 enters its second 5-year phase, the
      provision of low-vision services and their integration into national eyecare
      programs is a priority. In Pakistan, planning must take account of the magnitude
      along with the demographic and educational characteristics of those affected.

PMID- 18326709
TI  - Photodynamic therapy for corneal neovascularization using polymeric micelles
      encapsulating dendrimer porphyrins.
AB  - PURPOSE: To investigate the accumulation of new photosensitizers (PSs), dendrimer
      porphyrin (DP, free DP), and DP encapsulation into polymeric micelles (DP
      micelle) and the efficacy of photodynamic therapy (PDT) in an experimental
      corneal neovascularization model in mice. METHODS: Corneal neovascularization was
      induced by suturing 10-0 nylon 1 mm away from the limbal vessel in C57BL6/J mice.
      To determine the accumulation of free DP and DP-micelle, 10 mg/kg free DP or DP
      micelle was administered by intravenous injection 4 days after suture placement.
      Mice were killed 1, 4, 24, and 168 hours after the injection of PS. Twenty-four
      hours after the administration of free DP or DP-micelle, mice were treated with a
      diode laser of 438-nm wavelength at 10 or 50 J/cm(2). Fluorescein angiography was
      performed before and 7 days after irradiation, and the area of corneal
      neovascularization was quantified. RESULTS: Free DP and DP-micelle accumulated in
      the neovascularized area 1 hour to 24 hours after administration. Fluorescence of
      DP was weaker than that of DP-micelle. Neither DP-micelle nor DP could be
      detected in normal limbal vasculature. In the PDT experiments using PS, mean
      residual rates of corneal neovascularization were 10.1% in the mice treated with
      DP-micelle and 21.6% in the mice treated with free DP at 10 J/cm(2) (P < 0.01).
      At 50 J/cm(2), mean residual rates of corneal neovascularization were 10.6% in
      the mice treated with DP-micelle and 13.7% in the mice treated with free DP (P >
      0.05). Although corneal neovascularization in PDT-treated mice exhibited
      significant regression compared with the control group, significant energy
      related vessel regression with increasing laser energy could not be observed.
      CONCLUSIONS: PDT with DP-micelle and free DP can provide efficacious treatment of
      corneal neovascularization.

PMID- 18326710
TI  - Role of small GTPase Rho in regulating corneal epithelial wound healing.
AB  - PURPOSE: To determine the role of small GTPase Rho and its relation with
      epidermal growth factor receptor (EGFR) in mediating corneal epithelial wound
      healing. METHODS: Rho activity in THCE cells, an SV40-immortalized human corneal
      epithelial cell (HCEC) line, and primary HCECs was assessed by pull-down assay
      followed by Western blotting. Rho functions were inhibited with specific
      inhibitor exoenzyme C3 (C3) and confirmed by knockdown with small interference
      RNA (siRNA) transfection. Effects of Rho inhibition on wound healing were
      determined in porcine corneal organ culture and HCEC scratch wound models.
      Effects of C3 on cell proliferation and focal adhesion formation were determined
      by BrdU incorporation assay and immunocytochemistry, respectively. RESULTS:
      Wounding, lysophosphatidic acid, and heparin-binding EGF-like growth factor (HB
      EGF) induced rapid and strong RhoA activation. HB-EGF-, but not wounding-,
      enhanced RhoA activity was sensitive to EGFR inhibition. In corneal organ and
      cell culture models, C3 attenuated spontaneous and HB-EGF-induced wound closures,
      confirmed by delayed wound healing in cells transfected with RhoA siRNA. C3 also
      retarded spontaneous wound healing in the presence of hydroxyurea, a cell cycle
      blocker. C3 significantly reduced the number of BrdU-positive cells near the
      leading edge. Treatment with C3 resulted in the disruption of the cortical actin
      cytoskeleton and in the disappearance of paxillin-containing focal adhesion and
      lamellipodia. CONCLUSIONS: Wounding induces RhoA activation through an EGFR
      independent pathway. Rho activity is required for modulating cell migration and
      proliferation through cytoskeleton reorganization and focal adhesion formation in
      response to wounding.

PMID- 18326711
TI  - Age-related changes in rat corneal epithelial nerve density.
AB  - PURPOSE: To determine the effect of aging on corneal epithelial nerve density in
      an animal model. METHODS: Corneal whole mounts from rats aged 6, 12, 18, and 24
      months were stained immunohistochemically with antisera against the pan-neuronal
      marker neurotubulin. Epithelial nerve terminals and subbasal nerves in
      standardized 1-mm(2) central and peripheral zones from each cornea were drawn
      using a drawing tube attached to a light microscope. Images were scanned, and
      nerve densities were calculated as the percentage of each 1-mm(2) area occupied
      by nerves. The diameters of subbasal nerves in 6- and 24-month old animals were
      measured. Subbasal nerve vortices were analyzed qualitatively with reference to
      location, morphologic appearance, and directionality. RESULTS: Epithelial nerve
      terminal density decreased by approximately 50% between 6 and 24 months. The rate
      of decline was roughly linear and similar in both central and peripheral cornea.
      In contrast, subbasal nerve density increased by more than 50% between 6 and 24
      months in both central and peripheral cornea. The mean diameter of corneal
      subbasal nerves decreased approximately 30% (0.384 microm vs. 0.271 microm)
      between 6 and 24 months. The morphologic appearance and directionality of the
      subbasal nerve vortex demonstrated considerable interanimal variability and did
      not correlate with age. CONCLUSIONS: Rat corneal nerve terminal density
      decreases, but corneal subbasal nerve density increases, as a function of age.
      The age-related loss of nerve terminal density seen in the rat cornea is in
      keeping with the decreased corneal sensitivity reported in elderly humans and may
      contribute to the pathogenesis of dry eye disease in aged persons.

PMID- 18326712
TI  - Humphrey Matrix perimetry in optic nerve and chiasmal disorders: comparison with
      Humphrey SITA standard 24-2.
AB  - PURPOSE: To compare the Humphrey Matrix 24-2 perimetry (Matrix; Carl Zeiss
      Meditec, Inc., Dublin, CA) with the standard automated perimetry Humphrey Visual
      Field Analyzer using SITA (Swedish Interactive Threshold Algorithm) program 24-2
      (SAP; Carl Zeiss Meditec, Inc.) in neuro-ophthalmic disorders affecting the optic
      nerve and chiasm. METHODS: Matrix and SAP were performed on 93 patients with
      neuro-ophthalmic disorders affecting the optic nerve and optic chiasm. Three
      readers compared the total and pattern deviation probability plots and judged the
      similarity and the extent of the visual field defects. The sensitivity and
      specificity of both perimeters were calculated. RESULTS: Concordance was good in
      61%, fair in 30%, and poor in 9% of the total deviation plots. For the pattern
      deviation, concordance was good in 52%, fair in 34%, and poor in 14%. The extent
      of field loss was equal in 50%, 23% more extensive with Matrix, and 27% more
      extensive with SAP for total deviation plots. For the pattern deviation, the
      extent was equal in 47%, 20% more extensive with Matrix and 33% more extensive
      with SAP. The sensitivity for detecting defects was 84% (SAP) and 77% (Matrix)
      for total deviation and 80% (SAP) and 79% (Matrix) for pattern deviation (no
      significant difference, P > 0.05). The specificity was 84% (SAP) and 86% (Matrix)
      for total deviation and 68% (SAP) and 74% (Matrix) for pattern deviation (no
      significant difference, P > 0.05). CONCLUSIONS: The new Humphrey Matrix 24-2
      testing strategy provides a visual field testing method for optic nerve and
      chiasmal disorders that has fair to good concordance with the Humphrey SITA
      Standard 24-2 program. Both tests have similar sensitivity and specificity.

PMID- 18326713
TI  - Sensitivity and specificity of the Humphrey Matrix to detect homonymous
      hemianopias.
AB  - PURPOSE: To compare the sensitivity and specificity of the Humphrey Matrix
      frequency-doubling perimeter (Carl Zeiss Meditec, Inc., Dublin, CA) to that of
      standard automated perimetry (SAP) in detecting homonymous hemianopic visual
      field defects. METHODS: Thirty-three patients with homonymous hemianopias and 50
      normal subjects were tested with SAP with the Humphrey Visual Field Analyzer
      (SITA standard program 24-2) and Humphrey Matrix frequency-doubling perimetry,
      program 24-2 (Matrix) on the same day. Patients with hemianopias had lesions of
      the retrochiasmal visual system that were documented by magnetic resonance
      imaging or by computed tomography. To be classified as a hemianopic visual field
      defect, the abnormal test location had to be homonymous, respect the vertical
      meridian, and have no additional scattered abnormal points that obscured the
      hemianopic pattern. The sensitivity and specificity of SAP and Matrix in
      detecting hemianopic defects were calculated. The chi(2) test was used to test
      for differences between groups. RESULTS: The sensitivity for hemianopic defects
      by total deviation probability plots was 75% for SAP and 59% for Matrix (not
      statistically significant, P = 0.29). The sensitivity of hemianopic defects by
      pattern deviation probability plots was 88% for SAP and 69% for Matrix (not
      statistically significant, P = 0.13). The specificity of total deviation
      probability plots was 84% for SAP and 86% for Matrix. The specificity of the
      pattern deviation probability plots was 68% for SAP and 74% for Matrix.
      CONCLUSIONS: Although there was no statistically significant difference between
      the Matrix and SAP in the detection of hemianopias, the sensitivity of SAP was
      higher, probably because of the obscuration of defects by scattered abnormal test
      locations with the Matrix.

PMID- 18326714
TI  - Effect on diurnal intraocular pressure variation of eliminating the alpha-2
      adrenergic receptor subtypes in the mouse.
AB  - PURPOSE: To investigate the effect on circadian variation of intraocular pressure
      (IOP) of eliminating the alpha2A-, alpha2B-, or the alpha2C-adrenergic receptor
      subtypes in the mouse. METHODS: A microneedle method was used to measure IOP in
      knockout mice lacking the alpha2A-, alpha2B-, or the alpha2C-receptor (alpha2A-R(
      /-), alpha2B-R(-/-), alpha2C-R(-/-)), in wild-type mice of the alpha2B knockout
      strain (alpha2B-R(+/+)), and in the background strain mice, C57BL/6. All mice
      were maintained in a 12-hour light-dark cycle commencing at 0600 hours. IOP was
      measured at 0900 and 2100 hours in the five groups: C57BL/6 (n = 8), alpha2A-R(-/
      ) (n = 10), alpha2B-R(-/-) (n = 8), alpha2B-R(+/+) (n = 8), and alpha2C-R(-/-) (n
      = 10). In parallel experiments, eyes from the alpha2A-R(-/-), alpha2B-R(-/-),
      alpha2C-R(-/-), and C57BL/6 mice were embedded in epoxy resin, and semithin
      sections were stained with toluidine blue. RESULTS: IOP at 0900 hours in B6,
      alpha2A-R(-/-), alpha2B-R(-/-), alpha2B-R(+/+), and alpha2C-R(-/-) mice was 17.1
      +/- 1.8, 17.7 +/- 1.4, 17.1 +/- 2.1, 17.6 +/- 1.3, and 17.3 +/- 0.9 mm Hg,
      respectively (mean +/- SD). IOP at 2100 hours in the same eyes was 19.6 +/- 1.9,
      19.2 +/- 2.2, 20.5 +/- 1.5, 19.7 +/- 0.8, and 21.3 +/- 2.7 mm Hg, respectively.
      There was no significant difference among these genotypes in IOP measured at
      either time point (P > 0.05, ANOVA). Within each genotype, IOP at 2100 hours was
      significantly higher than IOP at 0900 hours (C57BL/6, alpha2B-R(-/-), alpha2B
      R(+/+), and alpha2C-R(-/-): P < 0.01; alpha2A-R(-/-): P < 0.05, paired t-test).
      Differences in the diurnal IOP change among the different genotypes were
      insignificant (P > 0.05, ANOVA). Histopathologic assessment found minimal
      differences in the structural organization of the anterior segment among the
      alpha2A-R(-/-), alpha2B-R(-/-),alpha2C-R(-/-), or C57BL/6 mice. CONCLUSIONS:
      These results indicate that IOP magnitude and circadian variation are minimally
      altered by the absence of the alpha2A-, alpha2B-, or alpha2C-receptor subtypes in
      transgenic mice.

PMID- 18326715
TI  - Continuous positive airway pressure therapy is associated with an increase in
      intraocular pressure in obstructive sleep apnea.
AB  - PURPOSE: Several reports have demonstrated an association between glaucoma and
      obstructive sleep apnea (OSA), though the origin of this association remains
      unknown. In the present study, the influence of OSA and continuous positive
      airway pressure (CPAP) therapy on intraocular pressure (IOP) and ocular perfusion
      pressure (OPP) was examined. METHODS: IOP, blood pressure, and pulse rate were
      measured every 2 hours during 24-hour sessions in 21 patients with newly
      diagnosed OSA. A first series of measurements was performed before CPAP therapy,
      and a second series was performed 1 month after the initiation of CPAP therapy.
      OPP was then calculated. RESULTS: Baseline measurements showed a significant
      nycththemeral fluctuation in the average IOP, with the highest IOPs at night.
      After 1 month of CPAP therapy, the average IOP was significantly higher than
      baseline. The increase in overnight IOP was also significantly higher. A 24-hour
      IOP fluctuation of > or =8 mm Hg was found in 7 patients at baseline and in 12
      patients during CPAP therapy. The mean difference between trough and peak IOP was
      6.7 +/- 1.5 mm Hg at baseline and 9.0 +/- 2.0 mm Hg during CPAP therapy. Thirty
      minutes after CPAP cessation a significant decrease in IOP was recorded. There
      was a statistically significant decrease in mean OPP during CPAP therapy.
      CONCLUSIONS: Patients with OSA demonstrated significant 24-hour IOP fluctuations,
      with the highest values at night. CPAP therapy causes an additional IOP increase,
      especially at night. Regular screening of visual fields and the optic disc is
      warranted for all patients with OSA, especially those treated with CPAP.

PMID- 18326716
TI  - Morphometric analysis of human peripapillary retinal nerve fiber layer thickness.
AB  - PURPOSE: The peripapillary retinal nerve fiber layer (RNFL) thickness pattern in
      the normal human eye has been well characterized using data obtained with
      scanning laser polarimetry and optical coherence tomography. The authors sought
      to characterize the normative peripapillary RNFL thickness and pattern using
      histologic sections obtained from healthy postmortem human eyes. METHODS:
      Seventeen unpaired normal postmortem eyes were recruited into this study. Each
      eye was sectioned using the "umbrella technique" to obtain four concentric
      peripapillary rings, each centered on the optic disc, with diameters of 3.0, 3.5,
      4.0, and 4.5 mm. RNFL thickness data along each ring section was measured at 100
      equidistant locations. Thickness data, for each ring diameter, across all eyes
      were averaged to arrive at normative thickness values for the peripapillary RNFL
      thickness in eyes processed using this technique. RESULTS: Average RNFL
      thicknesses (+/-SD) for the 3.5-mm diameter ring were as follows: overall, 60.3
      +/- 19.5 microm; superior, 75.3 +/- 26.5 mum; inferior, 69.4 +/- 22.4 microm;
      nasal, 48.1 +/- 15 microm; temporal, 49.2 +/- 26.4 microm. Qualitatively, the
      RNFL thickness showed a double-hump pattern with relatively similar superior and
      inferior peaks and with temporal and nasal troughs. Progressively larger
      peripapillary rings showed progressively thinner RNFL thickness at all quadrants.
      In contrast, the relative thickness percentage for each quadrant remained
      unchanged among the four different diameter rings. CONCLUSIONS: Histologic data
      from a group of healthy postmortem eyes demonstrate the pattern of RNFL thickness
      in normal eyes. These data corroborate imaging findings of peripapillary RNFL
      thickness patterns obtained using commercially available RNFL imaging devices.

PMID- 18326717
TI  - Bayesian machine learning classifiers for combining structural and functional
      measurements to classify healthy and glaucomatous eyes.
AB  - PURPOSE: To determine whether combining structural (optical coherence tomography,
      OCT) and functional (standard automated perimetry, SAP) measurements as input for
      machine learning classifiers (MLCs; relevance vector machine, RVM; and subspace
      mixture of Gaussians, SSMoG) improves diagnostic accuracy for detecting
      glaucomatous eyes compared with using each measurement method alone. METHODS:
      Sixty-nine eyes of 69 healthy control subjects (average age, 62.0, SD 9.7 years;
      visual field mean deviation [MD], -0.70, SD 1.41 dB) and 156 eyes of 156 patients
      with glaucoma (average age, 66.4, SD 10.2 years; visual field MD, -3.12, SD 3.43
      dB) were imaged with OCT (Stratus OCT, Carl Zeiss Meditec, Inc., Dublin, CA) and
      tested with SAP (Humphrey Field Analyzer II with Swedish Interactive Thresholding
      Algorithm, SITA; Carl Zeiss Meditec, Inc.) within 3 months of each other. RVM and
      SSMoG MLCs were trained and tested on OCT-determined RNFL thickness measurements
      from 32 sectors ( approximately 11.25 degrees each) obtained in the
      circumpapillary area under the instrument-defined measurement ellipse and SAP
      pattern deviation values from 52 points from the 24-2 grid, independently and in
      combination. Tenfold cross-validation was used to train and test classifiers on
      unique subsets of the full 225-eye data set, and areas under the receiver
      operating characteristic curve (AUROC) for the classification of eyes in the test
      set were generated. AUROC results from classifiers trained on OCT and SAP alone
      and those trained on OCT and SAP in combination were compared. In addition, these
      results were compared to currently available OCT measurements (mean retinal nerve
      fiber layer [RNFL] thickness, inferior RNFL thickness, and superior RNFL
      thickness) and SAP indices (MD and pattern standard deviation [PSD]). RESULTS:
      The AUROCs for RVM trained on OCT parameters alone, SAP parameters alone and OCT
      and SAP parameters combined were 0.809, 0.815, and 0.845, respectively. The
      AUROCs for SSMoG trained on OCT parameters alone, SAP parameters alone, and OCT
      and SAP parameters combined were 0.817, 0.841, and 0.869, respectively. Combining
      techniques using both RVM and SSMoG significantly improved on MLC analysis of
      OCT, but not SAP, measurements alone. Classification performance using RVM and
      SSMoG was statistically similar. CONCLUSIONS: RVM and SSMoG Bayesian MLCs trained
      on OCT and SAP data can successfully discriminate between healthy and early
      glaucomatous eyes. Combining OCT and SAP measurements using RVM and SSMoG
      increased diagnostic performance marginally compared with MLC analysis of data
      obtained using each technology alone.

PMID- 18326718
TI  - Diagnostic accuracy of the Matrix 24-2 and original N-30 frequency-doubling
      technology tests compared with standard automated perimetry.
AB  - PURPOSE: To compare the diagnostic accuracy of the Matrix frequency-doubling
      technology (FDT) 24-2, first-generation FDT N-30 (FDT N-30), and standard
      automated perimetry (SAP) tests of visual function. METHODS: One eye of each of
      85 glaucoma patients and 81 healthy controls from the Diagnostic Innovations in
      Glaucoma Study was included. Evidence of glaucomatous optic neuropathy on
      stereophotographs was used to classify the eyes. Matrix FDT 24-2, first
      generation FDT N-30, and SAP-SITA 24-2 tests were performed on all participants
      within 3 months. Receiver operating characteristic (ROC) curves were generated
      and used to determine sensitivity levels at 80% and 90% specificity for mean
      deviation (MD), pattern standard deviation (PSD), number of total deviation (TD),
      and pattern deviation (PD) points triggered at less than 5% and 1%. The tests
      were compared using the best parameter for each test (that with the highest area
      under the ROC curve) and with the PSD. RESULTS: The best parameters were MD for
      SAP (0.680), PSD for FDT N-30 (0.733), and number of TD less than 5% points for
      FDT 24-2 (0.774). Using the best parameter, the area under the ROC curve was
      significantly larger for FDT 24-2 than for SAP (P = 0.01). No statistically
      significant differences were observed between SAP and FDT N-30 (P = 0.21) and FDT
      N-30 and FDT 24-2 (P = 0.26). Similar results were obtained when the PSD was used
      to compare the tests, with the exception that the area under the ROC curve for
      the FDT N-30 test (0.733) was significantly larger than that of the SAP-SITA
      (0.641; P = 0.03). CONCLUSIONS: The performance of the Matrix FDT 24-2 was
      similar to that of the first-generation FDT N-30. The Matrix FDT 24-2 test was
      consistently better than SAP at discriminating between healthy and glaucomatous
      eyes. Further studies are needed to evaluate the ability of the Matrix FDT 24-2
      to monitor glaucoma progression.

PMID- 18326719
TI  - Acute endothelin-1 application induces reversible fast axonal transport blockade
      in adult rat optic nerve.
AB  - PURPOSE: To investigate the effects of endothelin (ET)-1 on fast axonal transport
      in the optic nerve. METHODS: Sterile sponge soaked in 1 nM ET-1 was applied to
      the optic nerve surface of adult Brown Norway rats for 1 hour, after which 20%
      horseradish peroxidase (HRP) was placed over the superior colliculi (SC). Rats
      were killed 2, 4, 6, 24, and 48 hours later; the retinas and optic nerves were
      removed and fixed; and cut sections were processed histochemically, to visualize
      the time course of HRP transport by light microscopy. Naive and saline controls
      were processed identically. Retinal ganglion cell (RGC) survival after acute ET-1
      application was investigated in another group of animals. After retrograde
      labeling of RGCs with the fluorescent neurotracer Fluorochrome (FG; Fluorogold;
      Fluorochrome Inc., Denver, CO), 1 nM ET-1 was applied to the optic nerve. Rats
      were then killed 5, 10, and 21 days later. The retinas were whole mounted and FG
      positive RGCs were imaged and quantified with fluorescence microscopy. RESULTS:
      In naive controls, HRP labeling was observed over the entire nerve at 2 hours but
      had cleared by 48 hours. HRP labeling of RGCs started at 6 hours, and by 48
      hours, uniform labeling was seen throughout the retina. In ET-1-treated optic
      nerves, transport of HRP was arrested at the distal portion of the nerve at 2
      hours. Recovery of transport was evident from 4 hours. At 6 and 24 hours, all
      nerves showed full recovery with HRP-positive RGCs in the retina, but the ratio
      of the RGC counts in treated versus fellow untreated eyes (0.66 +/- 0.13 and 0.67
      +/- 0.17, respectively) was less than that of the naive control (1.02 +/- 0.28
      and 1.05 +/- 0.13, respectively) animals. At 48 hours, recovery was complete, and
      there was no significant difference in the ratio of RGC counts between ET-1 and
      naive control groups. No RGC loss was observed after ET-1 application.
      CONCLUSIONS: Local acute application of ET-1 produces a reversible blockade of
      rapid axonal transport in optic nerve.

PMID- 18326720
TI  - Reproducibility and clinical relevance of the ocular response analyzer in
      nonoperated eyes: corneal biomechanical and tonometric implications.
AB  - PURPOSE: To assess the reproducibility of the ocular response analyzer (ORA) in
      nonoperated eyes and the impact of corneal biomechanical properties on
      intraocular pressure (IOP) measurements in normal and glaucomatous eyes. METHODS:
      In the reliability study, two independent examiners obtained repeated ORA
      measurements in 30 eyes. In the clinical study, the examiners analyzed ORA and
      IOP-Goldmann values from 220 normal and 42 glaucomatous eyes. In both studies,
      Goldmann-correlated IOP measurement (IOP-ORAg), corneal-compensated IOP (IOP
      ORAc), corneal hysteresis (CH), and corneal resistance factor (CRF) were
      evaluated. IOP differences of 3 mm Hg or greater between the IOP-ORAc and IOP
      ORAg were considered outcome significant. RESULTS: Intraexaminer intraclass
      correlation coefficients and interexaminer concordance correlation coefficients
      ranged from 0.78 to 0.93 and from 0.81 to 0.93, respectively, for all parameters.
      CH reproducibility was highest, and the IOP-ORAg readings were lowest. The median
      IOP was 16 mm Hg with the Goldmann tonometer, 14.5 mm Hg with IOP-ORAg (P <
      0.001), and 15.7 mm Hg with IOP-ORAc (P < 0.001). Outcome-significant results
      were found in 77 eyes (29.38%). The IOP-ORAc, CH, and CRF were correlated with
      age (r = 0.22, P = 0.001; r = -0.23, P = 0.001; r = -0.14, P = 0.02,
      respectively), but not the IOP-ORAg or IOP-Goldmann. CONCLUSIONS: The ORA
      provides reproducible corneal biomechanical and IOP measurements in nonoperated
      eyes. Considering the effect of ORA, corneal biomechanical metrics produces an
      outcome-significant IOP adjustment in at least one quarter of glaucomatous and
      normal eyes undergoing noncontact tonometry. Corneal viscoelasticity (CH) and
      resistance (CRF) appear to decrease minimally with increasing age in healthy
      adults.

PMID- 18326721
TI  - Blocking LINGO-1 function promotes retinal ganglion cell survival following
      ocular hypertension and optic nerve transection.
AB  - PURPOSE: LINGO-1 is a functional member of the Nogo66 receptor (NgR1)/p75 and
      NgR1/TROY signaling complexes that prevent axonal regeneration through RhoA in
      the central nervous system. LINGO-1 also promotes cell death after neuronal
      injury and spinal cord injury. The authors sought to examine whether blocking
      LINGO-1 function with LINGO-1 antagonists promotes retinal ganglion cell (RGC)
      survival after ocular hypertension and optic nerve transection. METHODS: An
      experimental ocular hypertension model was induced in adult rats using an argon
      laser to photocoagulate the episcleral and limbal veins. LINGO-1 expression in
      the retinas was investigated using immunohistochemistry and Western blotting.
      Soluble LINGO-1 protein (LINGO-1-Fc) and anti-LINGO-1 mAb 1A7 were injected into
      the vitreous body to examine their effects on RGC survival after ocular
      hypertension and optic nerve transection. Signal transduction pathways mediating
      neuroprotective LINGO-1-Fc effects were characterized using Western blotting and
      specific kinase inhibitors. RESULTS: LINGO-1 was expressed in RGCs and up
      regulated after intraocular pressure elevation. Blocking LINGO-1 function with
      LINGO-1 antagonists, LINGO-1-Fc and 1A7 significantly reduced RGC loss 2 and 4
      weeks after ocular hypertension and also promoted RGC survival after optic nerve
      transection. LINGO-1-Fc treatment blocked the RhoA, JNK pathway and promoted Akt
      activation. LINGO-1-Fc induced Akt phosphorylation, and the survival effect of
      LINGO-1 antagonists was abolished by Akt phosphorylation inhibitor. CONCLUSIONS:
      The authors demonstrated that blocking LINGO-1 function with LINGO-1 antagonists
      rescues RGCs from cell death after ocular hypertension and optic nerve
      transection. They also delineated the RhoA and PI-3K/Akt pathways as the
      predominant mediator of LINGO-1-Fc neuroprotection in this paradigm of RGC death.

PMID- 18326722
TI  - Time-dependent effects of elevated intraocular pressure on optic nerve head
      axonal transport and cytoskeleton proteins.
AB  - PURPOSE: To study the time-dependent effects of elevated intraocular pressure
      (IOP) on axonal transport and cytoskeleton proteins in the porcine optic nerve
      head. METHODS: Fifteen pigs were used for this study. Rhodamine-beta
      isothiocyanate was injected into the vitreous of each eye to study axonal
      transport. IOP in the left eye was elevated to 40 to 45 mm Hg, and IOP in the
      right eye was maintained between 10 and 15 mm Hg. Cerebrospinal fluid pressure
      was also continually monitored. IOP was elevated for 3 hours (n = 7) or 12 hours
      (n = 8) before animal euthanatization. Antibodies to phosphorylated neurofilament
      heavy (NFHp), phosphorylation-independent neurofilament heavy (NFH),
      neurofilament light, neurofilament medium (NFM), microtubule, and microtubule
      associated protein (MAP) were used to study the axonal cytoskeleton. Confocal
      microscopy was used to compare axonal transport and cytoskeleton change between
      control and high IOP eyes in different laminar regions and quadrants of the optic
      nerve head. Results from these experiments were also compared with 6-hour
      elevated IOP data from an earlier study. RESULTS: Three hours of IOP elevation
      caused a decrease in NFH, NFHp, and NFM within laminar regions, with no
      demonstrable change in axonal transport. Changes to MAP and microtubules were
      only seen after 12 hours of IOP elevation. Axonal transport change occurred in a
      time-dependent manner with peripheral nerve bundle changes occurring earlier and
      being greater than central nerve bundle changes. CONCLUSIONS: Time-dependent
      changes in axonal transport and cytoskeletal structure in the optic nerve head
      provide further pathogenic evidence of axonal damage caused by elevated IOP.

PMID- 18326723
TI  - Disruption of CFTR-dependent lipid rafts reduces bacterial levels and corneal
      disease in a murine model of Pseudomonas aeruginosa keratitis.
AB  - PURPOSE: Pseudomonas aeruginosa enters corneal epithelial cells in vitro via
      membrane microdomains or lipid rafts. Bacterial entry, mediated by the cystic
      fibrosis transmembrane conductance regulator (CFTR), promotes infection and
      disease. This study was conducted to determine whether P. aeruginosa and CFTR are
      colocalized to rafts in isogenic corneal cells expressing wild-type (WT) or
      mutant DeltaF508-CFTR and whether disruption of the rafts both in vitro and in
      vivo affects the bacterial levels and the course of the disease. METHODS:
      Transformed human corneal epithelial cells from a patient homozygous for
      DeltaF508-CFTR, and the same cells corrected with WT-CFTR, were exposed to six
      isolates of P. aeruginosa-three invasive and three cytotoxic strains-in the
      presence of beta-cyclodextrin (CD), which disrupts rafts. Association and
      cellular uptake of the invasive strains were measured, as was lactate
      dehydrogenase release induced by the cytotoxic strains. Scratch-injured mouse
      eyes were infected with the six P. aeruginosa strains, and the effect of
      prophylactic or therapeutic administration of CD on bacterial levels and disease
      was evaluated. RESULTS: P. aeruginosa and CFTR were colocalized with lipid rafts
      in cells with WT-CFTR, and CD treatment of these cells disrupted bacterial
      association, internalization, and cytotoxic effects. Cells expressing DeltaF508
      CFTR were marginally affected by CD. Prophylactic and therapeutic topical
      application of CD ameliorated corneal disease and reduced the bacterial count in
      the eye. CONCLUSIONS: P. aeruginosa enters human corneal epithelial cells via
      lipid rafts containing CFTR, and disruption of raft-mediated uptake of this
      organism by CD protects against disease and reduces bacterial levels in the mouse
      model of keratitis.

PMID- 18326724
TI  - Milk components inhibit Acanthamoeba-induced cytopathic effect.
AB  - PURPOSE: Acanthamoebae provoke a vision-threatening corneal infection known as
      Acanthamoeba keratitis (AK). It is thought that Acanthamoeba-specific IgA
      antibodies present in mucosal secretions such as human tears, milk, and saliva
      provide protection against infection by inhibiting the adhesion of parasites to
      host cells. The goal of the present study was to determine whether human mucosal
      secretions have the potential to provide protection against the Acanthamoeba
      induced cytopathic effect (CPE) by an additional mechanism that is independent of
      IgA. METHODS: Breast milk was used as a model of human mucosal secretions. In
      vitro CPE assays were used to examine the CPE inhibitory effect of IgA-depleted
      milk and various milk fractions obtained by gel filtration. The activity of
      amebic proteinases was examined by zymography. RESULTS: IgA-depleted milk
      inhibited the Acanthamoeba-induced CPE in a concentration-dependent manner. Milk
      proteins were separated into four major fractions (F1-F4) by gel filtration. Of
      these four fractions, CPE inhibitory activity was detected largely in fraction
      F3. In contrast, fractions F1, F2, and F4 lacked CPE inhibitory activity.
      Moreover, fraction F3, but not F1, F2, or F4, inhibited amebic proteinases.
      CONCLUSIONS: These data, in conjunction with published findings showing that
      amebic proteinases are responsible for the induction of Acanthamoeba CPE, led us
      to propose that human mucosal secretions have the potential to provide protection
      against Acanthamoeba-induced CPE by an additional mechanism that is independent
      of IgA and that involves the inhibition of cytotoxic proteinases of amebae.

PMID- 18326725
TI  - Susceptibility of ovine lens crystallins to proteolytic cleavage during formation
      of hereditary cataract.
AB  - PURPOSE: To produce two-dimensional electrophoresis (2-DE) maps for ovine
      crystallins and examine changes in ovine crystallins during cataract formation.
      METHODS: Soluble and insoluble fractions were isolated from normal, whole lenses
      of 26-week-old sheep, the proteins separated by 2-DE, and the spots digested with
      trypsin and subjected to tandem mass spectral analysis. Spot identifications were
      made by using mass spectrometry data from each spot digestion and data from 2-DE
      maps of proteins from soluble and insoluble cortices of 10-month-old ovine lens.
      Ovine alphaA-, alphaB-, and betaB3-crystallin cDNAs were sequenced, whereas other
      ovine crystallins were identified by using bovine sequences. Proteins were then
      isolated from whole lenses of 26-week-old lambs with mature hereditary cataracts,
      and the changes in the crystallins were determined by 2-DE. The masses of
      truncated crystallins were determined after elution from 2-DE gels. RESULTS: The
      ovine lens contained the normal complement of crystallins and, similar to other
      mammalian lenses, underwent partial proteolysis of betaB1-, betaA3-, and betaB3
      crystallin during maturation. Cataract development was associated with enhanced
      truncation of alpha- and beta-crystallins. C-terminal truncations of alphaA- and
      alphaB-crystallin and N-terminal truncation of betaB2-crystallin were observed as
      well as a loss of gamma-crystallin. CONCLUSIONS: These data provide the first 2
      DE gel maps for ovine lens crystallins and indicated that ovine lens crystallins
      are truncated during lens maturation. The differences in proteolysis appearing in
      normal and cataractous lenses suggested that calpain isoforms may be
      differentially activated during lens maturation and cataract. The ovine
      hereditary cataract is a useful nonrodent model to study the role of calpain
      proteolysis in cataract formation.

PMID- 18326726
TI  - Age-dependent control of lens growth by hypoxia.
AB  - PURPOSE: The lens grows continuously throughout life, but the factors that
      influence the size of the adult lens are not known. Lens thickness is a
      significant risk factor for age-related cataract. It has been postulated that the
      hypoxic environment in the eye protects the lens from nuclear cataracts. The
      authors sought to determine whether the Po(2) in the eye regulates lens growth.
      METHODS: Lens cell proliferation was determined by counting BrdU-labeled and
      total nuclei in the germinative zone in flatmounts of lens epithelia. Oxygen
      levels in the eye were altered by having rats breathe 11%, 21% (room air), or 60%
      oxygen. Oxygen levels in the vitreous were measured with a fiberoptic oxygen
      sensor. RESULTS: The BrdU-labeling index in the germinative zone declined from
      approximately 3.5% at 1 month to less than 0.7% at 8 months. Raising oxygen
      levels in the eyes of 1-month-old animals did not alter the rate of lens cell
      proliferation. Elevating intraocular oxygen in animals older than 1 month
      increased proliferation to the more rapid rate seen at 1 month. Decreasing oxygen
      levels below their normally low level did not affect the BrdU-labeling index at
      any age. Chronic exposure to increased oxygen led to the production of more lens
      fiber cells and larger lenses. CONCLUSIONS: Normal age-related decline in lens
      growth requires the low oxygen level normally present in the eye. Increases in
      lens cell number and mass may account for some of the increase in cataract risk
      caused by chronic exposure of the lens to elevated oxygen levels.

PMID- 18326727
TI  - Resisting the effects of aging: a function for the fiber cell beaded filament.
AB  - PURPOSE: The beaded filament is a cytoskeletal structure that has been found only
      in the lens fiber cell. It includes phakosin and filensin, two divergent members
      of the intermediate filament family of proteins that are also unique to the fiber
      cell. The authors sought to determine what function the beaded filament fulfills
      in the lens. METHODS: Light microscopy and electron microscopy were used to
      characterize structural changes that occurred in previously generated phakosin
      and filensin knockout mice. Immunocytochemistry and electron microscopy were used
      to define the distribution of phakosin, filensin, and beaded filaments. RESULTS:
      In phakosin and filensin knockout mice, initial lens development and the early
      phases of fiber cell differentiation proceed in a manner largely
      indistinguishable from that of wild type. Fiber cells elongate, undergo organelle
      elimination, and, in the organelle-free zone, develop the unique paddlelike
      extensions that characterize cells in this region. Subsequent to those stages,
      however, fiber cells undergo loss of the differentiated fiber cell phenotype and
      loss of the long-range stacking that characterizes fiber cells and that has been
      considered essential for clarity. CONCLUSIONS: The beaded filament is not
      required for the generation of the differentiated fiber cell phenotype but is
      required to maintain that differentiated state and the long range order that
      characterizes the lens at the tissue level.

PMID- 18326728
TI  - FK506-binding protein 51 regulates nuclear transport of the glucocorticoid
      receptor beta and glucocorticoid responsiveness.
AB  - PURPOSE: A spliced variant of the human glucocorticoid receptor GRbeta has been
      implicated in glucocorticoid responsiveness in glaucoma. Over-expression of the
      FK506-binding immunophilin FKBP51 also causes a generalized state of
      glucocorticoid resistance. In the present study, the roles of FKBP51 in the
      nuclear transport of GRbeta and glucocorticoid responsiveness were investigated.
      METHODS: Human trabecular meshwork cells (GTM3 and TM5) and HeLa cells were
      treated with dexamethasone (DEX) and FK506 and transfected with GRbeta and FKBP51
      expression vectors. Coimmunoprecipitation and Western blot analyses were
      performed to study interactions of FKBP51 and FKBP52 with GRalpha, GRbeta, Hsp90,
      or dynein. The cells were transfected with a GRE-luciferase reporter to evaluate
      the effects of DEX and FK506 and the overexpression of GRbeta and FKBP51 on
      glucocorticoid-mediated gene expression. RESULTS: FKBP51 was involved in
      constitutive nuclear transport of both GRalpha and -beta in the absence of
      ligands. FKBP52 appeared to be solely responsible for the nuclear transport of
      ligand-activated GRalpha. DEX stimulated the translocation of GRalpha but not
      GRbeta. Overexpression of either GRbeta or FKBP51 stimulated GRbeta translocation
      and reduced DEX-induced luciferase in HeLa cells. FK506 did not alter DEX-induced
      translocation of GRalpha. However, FK506 increased the association of FKBP51 with
      GRbeta and stimulated DEX-induced translocation of GRbeta in normal TM cells, but
      not in glaucoma TM cells. Increased nuclear GRbeta significantly inhibited
      glucocorticoid responsiveness in TM cells. CONCLUSIONS: Nuclear transport of
      GRbeta represents a novel mechanism through which FKBP51 alters GC sensitivity.
      GRbeta and FKBP51 may be responsible for increased responsiveness in steroid
      induced ocular hypertensive individuals as well as in patients with glaucoma.

PMID- 18326730
TI  - Quantification of ischemic damage in the rat retina: a comparative study using
      evoked potentials, electroretinography, and histology.
AB  - PURPOSE: To identify objective criteria to quantify visual function in the rat
      for developing therapeutic strategies to protect neuronal cells after ischemia.
      The impact of ocular ischemia on luminance and frequency-modulated contrast
      vision was compared with the function of outer retinal cells and the number of
      intact retinal ganglion cells (RGCs). METHOD: Ischemia was induced in Brown
      Norway rats by elevating the intraocular pressure to 120 mm Hg for 30, 45, 60,
      and 90 minutes. Visual function was evaluated by visual evoked potentials (VEPs)
      in awake, freely moving rats. Retinal function was analyzed with scotopic and
      photopic electroretinography (ERG). RGCs were quantified in retinal flatmounts
      after postischemic injection of tracer into the superior colliculus. RESULTS: The
      response to flicker stimulation in VEP recordings decreased as the ischemic
      episodes increased. The susceptibility to ischemic damage was more pronounced
      when potentials were evoked with stimuli at higher frequencies. In ERG
      recordings, ischemia reduced oscillatory potentials and photopic flicker
      responses more intensely than scotopic a- and b-waves. In counting the RGCs, the
      reduced cell density correlated significantly with all electrophysiological
      parameters. The duration of ischemia with half-maximal inhibitory effect was
      between 36 and 58 minutes for VEPs and between 36 and 41 minutes for ERG, and it
      was 51 minutes for RGCs. CONCLUSIONS: The amounts of reduction in VEPs, ERG, and
      RGCs differed as the duration of ischemia increased. The electrophysiological
      parameters presented in this study may serve as a useful addition to morphologic
      evaluations in future neuroprotection studies in vivo.

PMID- 18326729
TI  - Role of carbonic anhydrase IV in corneal endothelial HCO3- transport.
AB  - PURPOSE: Carbonic anhydrase activity has a central role in corneal endothelial
      function. The authors examined the role of carbonic anhydrase IV (CAIV) in
      facilitating CO(2) flux, HCO(3)(-) permeability, and HCO(3)(-) flux across the
      apical membrane. METHODS: Primary cultures of bovine corneal endothelial cells
      were established on membrane-permeable filters. Apical CAIV was inhibited by
      benzolamide or siRNA knockdown of CAIV. Apical CO(2) fluxes and HCO(3)(-)
      permeability were determined by measuring pH(i) changes in response to altering
      the CO(2) or HCO(3)(-) gradient across the apical membrane. Basolateral to apical
      (B-to-A) HCO(3)(-) flux was determined by measuring the pH of a weakly buffered
      apical bath in the presence of basolateral bicarbonate-rich Ringer solution. In
      addition, the effects of benzolamide and CAIV knockdown on steady state DeltapH
      (apical-basolateral compartment pH) after 4-hour incubation in DMEM were
      measured. RESULTS: CAIV expression was confirmed, and CAIV was localized
      exclusively to the apical membrane by confocal microscopy. Both 10 microM
      benzolamide and CAIV siRNA reduced apparent apical CO(2) flux by approximately
      20%; however, they had no effect on HCO(3)(-) permeability or HCO(3)(-) flux. The
      steady state apical-basolateral pH gradient at 4 hours was reduced by 0.12 and
      0.09 pH units in benzolamide- and siRNA-treated cells, respectively, inconsistent
      with a net cell-to-apical compartment CO(2) flux. CONCLUSIONS: CAIV does not
      facilitate steady state cell-to-apical CO(2) flux, apical HCO(3)(-) permeability,
      or B-to-A HCO(3)(-) flux. Steady state pH changes, however, suggest that CAIV may
      have a role in buffering the apical surface.

PMID- 18326731
TI  - Effect of unspecific inhibition of cyclooxygenase by indomethacin on retinal and
      choroidal blood flow.
AB  - PURPOSE: Animal studies suggest that retinal and choroidal blood flow decrease
      after administration of indomethacin, a nonspecific cyclooxygenase inhibitor.
      Cyclooxygenase is the key enzyme involved in the arachidonic pathway and
      regulates the production of vasoactive substances such as prostaglandins and
      thromboxans. The aim of the present study was to investigate the short-term
      effects of indomethacin on ocular blood flow in healthy humans. METHODS: A
      randomized, double-masked, placebo-controlled, two-way crossover study in 12
      healthy, male, nonsmoking subjects was performed. Indomethacin was administered
      as a bolus injection of 0.4 mg/kg followed by continuous infusion of 0.4 mg/kg/h
      over 120 minutes. Ocular hemodynamic parameters were measured at baseline and up
      to 3 hours after start of the infusion. Subfoveal choroidal blood flow and fundus
      pulsation amplitude were measured with laser Doppler flowmetry and laser
      interferometry, respectively. Retinal vessel diameters were assessed using a
      retinal vessel analyzer. Retinal blood flow was calculated based on retinal
      vessel diameters, and red blood cell velocity was measured with laser Doppler
      velocimetry. RESULTS: Administration of indomethacin decreased retinal arterial
      diameters up to -4.3% +/- 3.4% and reduced retinal blood velocity by a maximum of
      -29% +/- 20% (P < 0.05). Calculated retinal blood flow decreased by -27% +/- 21%
      (P < 0.05), reaching the maximal decrease 60 minutes after administration.
      Choroidal blood flow and fundus pulsation amplitude (FPA) also decreased during
      the infusion of indomethacin with maximum effects of -17% +/- 13% (P < 0.05, vs.
      placebo) and -7% +/- 4% (P < 0.05, vs. placebo), respectively. CONCLUSIONS:
      Results showed a marked decrease in retinal and choroidal blood flow after short
      term administration of indomethacin. Whether this decrease can be attributed to a
      reduced production of prostaglandins or an unknown mechanism has yet to be
      clarified. Further studies appear to be indicated to investigate whether the long
      term intake of indomethacin is associated with an increased risk for vascular eye
      disease.

PMID- 18326733
TI  - Phacoemulsification does not induce neovascular age-related macular degeneration.
AB  - PURPOSE: To investigate whether cataract surgery by phacoemulsification induces
      progression of early age-related macular degeneration (AMD) to neovascular AMD.
      METHODS: Retrospective case-control study. Included were consecutive patients who
      had undergone phacoemulsification from January 2000 to February 2006 at the
      Recklinghausen Eye Centre, who had a preexisting diagnosis of early AMD and who
      were followed up for at least 1 year after surgery (n = 1152 eyes of 696
      patients). The control group comprised phakic patients diagnosed with early AMD
      from January 2000 to February 2006, who did not undergo eye surgery and were
      followed up for at least 1 year (n = 334 eyes of 202 patients). RESULTS: At
      baseline, control eyes had significantly better visual acuity than those of
      patients who were going to have cataract surgery (0.30/0.35 +/- 0.34 vs.
      0.40/0.49 +/- 0.34, respectively; median/mean +/- SD; P < 0.001, Mann-Whitney
      rank sum test). After 1 year, visual acuity in the control group was worse than
      in surgical eyes (0.30/0.39 +/- 0.38 vs. 0.20/0.26 +/- 0.30, respectively;
      median/mean +/- SD; P < 0.001, Mann-Whitney rank sum test). In the cataract
      surgery group, neovascular AMD developed in 28 (2.43%) of 1152 eyes in the first
      postoperative year. In the control group, it developed in 6 (1.74%) of 344 eyes
      within 1 year. There was no significant difference between the groups in the
      incidence of neovascular AMD (P = 0.57, odds ratio 1.30, 95% CI 0.52-3.24,
      logistic regression analysis, adjusted for age and baseline visual acuity).
      CONCLUSIONS: The results indicate that cataract surgery in eyes with early AMD is
      not a causative factor in neovascular AMD.

PMID- 18326732
TI  - Retinol dehydrogenases RDH11 and RDH12 in the mouse retina: expression levels
      during development and regulation by oxidative stress.
AB  - PURPOSE: RDH11 and RDH12 are closely related retinol dehydrogenases expressed in
      the retina. RDH12 has been linked to the early-onset retinal dystrophy Leber
      congenital amaurosis, whereas RDH11 has not been associated with human disease.
      To understand their physiological roles, the authors investigated their
      expression during development and their regulation by light-induced oxidative
      stress in mouse retina. METHODS: Quantitative RT-PCR and immunoblot analysis were
      used for quantification of RDH11 and RDH12 during development and oxidative
      stress. Expression during development was measured between embryonic day (E) 12
      and postnatal day (P) 210 (7 months) in C57BL/6 mouse eyes. Expression during
      light-induced oxidative stress was measured between 2 and 24 hours of exposure to
      light in BALB/c mouse retina. RESULTS: The RDH11 level was low and remarkably
      constant during development and oxidative stress. RDH12 expression started at P7
      and increased until P30 to approximately sevenfold higher than RDH11. Oxidative
      stress induced by exposure to constant bright light led to a rapid and
      significant decrease of RDH12 protein. CONCLUSIONS: The low and constant
      expression of RDH11 suggested a housekeeping function for this enzyme. The onset
      of RDH12 expression during the maturation of photoreceptor cells suggested a
      function related to the visual process. The light-induced rapid decrease of RDH12
      protein, preceding the decrease of the mRNA, suggested a specific degradation of
      the protein rather than a regulation of gene expression.

PMID- 18326734
TI  - Repeatability of stratus optical coherence tomography measures in neovascular age
      related macular degeneration.
AB  - PURPOSE: To determine the repeatability of Stratus optical coherence tomography
      (OCT) measures of retinal thickness and volume in patients with neovascular age
      related macular degeneration (nAMD) METHOD: Fifty-one eyes of 51 consecutive
      patients with nAMD underwent an OCT imaging session in which two fast macular
      thickness map (FMTM) protocol scans sets were acquired by a single experienced
      operator certified for clinical trials work. Coefficients of repeatability for
      each of nine Early Treatment of Diabetic Retinopathy Study (ETDRS)-like regions,
      foveolar center-point retinal thickness (CPT) and total macular volume (TMV),
      were calculated. Scans were analyzed retrospectively for errors in retinal
      boundary placement by two observers, with revised coefficients of repeatability
      calculated after excluding any scan sets with significant segmentation error.
      RESULTS: The coefficient of repeatability for the central 1-mm macular subfield
      was 67 mum (23%) and was less than 75 mum for all macular subfields. There was
      much larger variability in the center-point thickness measure, with a coefficient
      of repeatability of 88 mum (32%) for the automated center-point thickness (ACPT).
      After excluding nine scan set pairs with significant segmentation error, the
      coefficient of repeatability for the central 1-mm macular subfield was reduced to
      50 mum (19%). CONCLUSIONS: OCT-derived retinal thickness measurements are subject
      to considerable measurement variability in patients with nAMD. Changes in central
      macular thickness of more than 50 mum may better reflect true clinical change in
      scan sets without significant segmentation error and may be used to guide the
      retreatment of patients with nAMD in clinical trials and clinical practice.

PMID- 18326735
TI  - rd1 Mouse retina shows an imbalance in the activity of cysteine protease
      cathepsins and their endogenous inhibitor cystatin C.
AB  - PURPOSE: To compare in vivo levels, spatial localization, and in vitro secretion
      of cysteine protease cathepsins and cystatin C (cysC) in the retinal degeneration
      1 (rd1) mouse model of retinitis pigmentosa and control (wt) mouse retinas.
      METHODS: The spatial localization, protein contents, cysC levels and cathepsin-B,
      -S, and -L activities in wt and rd1 retinas at postnatal (PN) days 2, 7, 14, 21,
      and 28 were analyzed by immunostaining, spectrophotometry, ELISA, and
      fluorescence spectrophotometry. The in vitro secretion of cysC and cysteine
      proteases by PN7 retinal explants into the conditioned medium (RCM) was
      quantified. RESULTS: The pigment epithelium, photoreceptors, and inner retinal
      and ganglion cell layers of both wt and rd1 retinas showed cysC and cathepsin-B
      labeling. CysC immunostaining was extensive in the optic nerve head fibers. The
      rd1 explants secreted higher amounts of cysteine protease into the RCM. The
      protein content in wt and rd1 retinal extracts increased up to PN14, then
      decreased in rd1 but not in wt. In rd1 extracts at PN14 to -28, cathepsin
      activity was higher and increased with age, but the cysC level was higher and
      constant. The ratios of cathepsin activity to cysC (cathepsin-L at PN2 and total,
      -B, and -L at PN14 to -28) were higher in rd1 extracts. CONCLUSIONS: Similar
      localization of both cathepsin-B and cysC in wt and rd1 retinas along with lower
      proteins and higher cathepsin activity in rd1 retinal extracts and RCM are
      consistent with their localization in extracellular matrix and a role in
      physiopathologic remodeling in wt and rd1 retinas.

PMID- 18326736
TI  - Subretinal bevacizumab detection after intravitreous injection in rabbits.
AB  - PURPOSE: To evaluate subretinal detection of bevacizumab 2 hours after
      intravitreous injection of 1.25 mg in rabbit eyes. METHODS: Anterior chamber
      paracentesis using a 30-gauge needle was performed in nine female Dutch-belted
      rabbits by removal of 0.05 mL of aqueous humor. Transscleral retinal detachment
      was performed with a modified 25-gauge infusion cannula connected to a bottle of
      physiologic saline solution (PSS). The animals were divided into experimental
      group 1, with intravitreous injection of 0.05 mL of (1.25 mg) with a 30-gauge
      needle (n = 6) and the control group 2, with intravitreous injection of 0.05 mL
      of PSS with a 30-gauge needle (n = 3). Two hours after the intravitreous
      bevacizumab or PSS injection, subretinal fluid was aspirated and immunoassayed to
      measure the level of bevacizumab. The rabbits were killed by intravenous
      pentobarbital injection. The eyes were enucleated and fixed in 10% formaldehyde.
      The pars plana site at which the transscleral cannula was introduced was analyzed
      by light microscopy, to exclude iatrogenic retinal tears. Eyes with accidental
      retinal tears were excluded. RESULTS: Subretinal bevacizumab molecules were
      detected in the six eyes that received an intravitreous bevacizumab injection. No
      subretinal bevacizumab was detected in the control eyes. Light microscopy showed
      no evidence of retinal tears or holes in any rabbits used for the bevacizumab
      detection and control group. CONCLUSIONS: Bevacizumab molecules were detected in
      the subretinal space after intravitreous injection of 1.25 mg of bevacizumab,
      possibly as the result of diffusion through the retina in a rabbit model.

PMID- 18326737
TI  - Elastin gene polymorphisms in neovascular age-related macular degeneration and
      polypoidal choroidal vasculopathy.
AB  - PURPOSE: To study and reveal genetic variation in the elastin gene (ELN) that may
      be associated with neovascular age-related macular degeneration (AMD) and/or
      polypoidal choroidal vasculopathy (PCV). Eyes with neovascular AMD and PCV
      exhibit substantially different structural alterations of the elastic layer in
      the Bruch's membrane. The hypothesis for the present study was that ELN
      polymorphisms may play a role in the development of neovascular AMD and PCV and
      that genetic differences in ELN between these two phenotypes may be a reason for
      the histopathologic differences. To test these hypotheses, ELN was screened for
      genetic variation in a Japanese case-control dataset. METHODS: Two hundred eighty
      five subjects were enrolled: 78 with neovascular AMD, 103 with PCV, and 104
      control. We genotyped five tagged single nucleotide polymorphisms (SNPs) in ELN,
      and allele, genotype, and haplotype frequency distributions among neovascular
      AMD, PCV, and control subjects were compared by chi(2) tests. RESULTS: A common
      ELN variant was significantly associated with susceptibility to PCV. The age- and
      sex-adjusted odds ratio was 7.56 for individuals homozygous for the risk allele
      compared with those carrying no more than one copy of the risk allele.
      Significantly different distributions were found in allele and haplotype
      frequencies between neovascular AMD and PCV in this region, but no particular ELN
      SNPs or haplotypes were significantly associated with neovascular AMD.
      CONCLUSIONS: The findings implicate ELN as a susceptibility gene for PCV, and
      suggest that a different pathogenic process may be involved in the phenotypic
      expression of neovascular AMD and PCV.

PMID- 18326738
TI  - Functional and structural changes in the retina of wire-haired dachshunds with
      early-onset cone-rod dystrophy.
AB  - PURPOSE: To describe and classify the morphologic changes in a naturally
      occurring dog model of early-onset cone-rod dystrophy (CRD) and to correlate
      these with earlier described clinical characteristics of the disease in dogs.
      METHODS: Purpose-bred Standard Wire-Haired Dachshunds (SWHDs) derived from a
      large pedigree of dogs with early-onset CRD were euthanatized at defined ages to
      characterize morphologic changes in the disease process. Specimens were examined
      by light microscopy, including morphometric studies, electron microscopy, and
      immunohistochemistry. Peanut agglutinin (PNA), protein kinase C (PKC),
      synaptophysin (Syn), rhodopsin (Rho)-63, glial fibrillary acidic protein (GFAP),
      and short-wavelength cone opsin (OS) were used for immunohistochemical
      characterization. RESULTS: The photopic cone-system-derived ERG amplitudes were
      already significantly reduced or nonrecordable in CRD-affected dogs at 5 weeks,
      the earliest age studied. The outer retina was morphologically most severely
      affected initially, with a subsequent degeneration of the inner retina. Cone
      degeneration was more pronounced than rod degeneration in young CRD-affected
      dogs. There was a marked phenotypic variation based on morphologic findings in
      the affected dogs. At the earliest time point studied (5-8 weeks) cone
      photoreceptor and glial cell abnormalities were observed, in accordance with
      earlier studies based on electrophysiological and clinical findings in which day
      blindness and abnormal cone ERGs were observed in young affected SWHD puppies.
      Preliminary genetic studies have indicated an autosomal recessive mode of
      inheritance for the defect. CONCLUSIONS: Through functional and structural
      characterization, early-onset cone abnormalities were found, consistent with a
      cone dysplasia at an age when rod structure was normal. Further studies are in
      progress to identify the gene(s) involved in this retinal disease process. The
      presently described natural animal model of primary cone dysplasia followed by
      rod degeneration may provide further insight into the human counterpart. Further
      studies are needed to ascertain an autosomal recessive mode of inheritance for
      CRD in the SWHD.

PMID- 18326739
TI  - The status of cones in the rhodopsin mutant P23H-3 retina: light-regulated damage
      and repair in parallel with rods.
AB  - PURPOSE: This study tests whether cones in the rhodopsin-mutant transgenic P23H-3
      retina are damaged by ambient light and whether subsequent light restriction
      allows repair of damaged cones. METHODS: P23H-3 rats were raised in scotopic
      cyclic (12 hours of 5 lux, 12 hours of dark) ambient light. At postnatal day 90
      to 130, some were transferred to photopic conditions (12 hours of 300 lux, 12
      hours of dark) for 1 week and then returned to scotopic conditions for up to 5
      weeks. Photoreceptor function was assessed by the dark-adapted flash-evoked
      electroretinogram, using a two-flash paradigm to isolate the cone response. Outer
      segment structure was demonstrated by immunohistochemistry for cone and rod
      opsins and by electron microscopy. RESULTS: Exposure for 1 week to photopic
      ambient light reduced the cone b-wave, the rod b-wave, and the rod a-wave by 40%
      to 60% and caused shortening and disorganization of cone and rod outer segments.
      Restoration of scotopic conditions for 2 to 5 weeks allowed partial recovery of
      the cone b-wave and the rod a- and b-waves, and regrowth of outer segments.
      CONCLUSIONS: Modest increases in ambient light cause rapid and significantly
      reversible loss of cone and rod function in the P23H-3 retina. The reduction and
      recovery of cone function are associated with shortening and regrowth of outer
      segments. Because the P23H mutation affects a protein expressed specifically in
      rods, this study emphasizes the close dependence of cones on rod function. It
      also demonstrates the capacity of cones and rods to repair their structure and
      regain function.

PMID- 18326740
TI  - Nrl-knockout mice deficient in Rpe65 fail to synthesize 11-cis retinal and cone
      outer segments.
AB  - PURPOSE: To define rod and cone function further in terms of visual cycle
      mechanism, the retinal phenotype resulting from Rpe65 (retinoid isomerase I)
      deficiency in Nrl(-)(/)(-) mice having a single class of photoreceptors
      resembling wild-type cones was characterized and outcomes of retinoid
      supplementation evaluated. METHODS: Rpe65(-)(/)(-)/Nrl(-)(/)(-) mice were
      generated by breeding Rpe65(-)(/)(-) and Nrl(-)(/)(-) strains. Retinal histology,
      protein expression, retinoid content, and electroretinographic (ERG) responses
      were evaluated before and after treatment with 11-cis retinal by intraperitoneal
      injection. Results Retinas of young Rpe65(-)(/-)/Nrl(-)(/-) mice exhibited normal
      lamination, but lacked intact photoreceptor outer segments at all ages examined.
      Rpe65, Nrl, and rhodopsin were not detected, and S-opsin and M/L-opsin levels
      were reduced. Retinyl esters were the only retinoids present. In contrast, Nrl(
      )(/)(-) mice exhibited decreased levels of retinaldehydes and retinyl esters, and
      elevated levels of retinols. ERG responses were elicited from Rpe65(-)(/-)/Nrl(
      )(/-) mice only at the two highest intensities over a 4-log-unit range.
      Significant retinal thinning and outer nuclear layer loss occurred in Rpe65(-)(/
      )/Nrl(-)(/-) mice with aging. Administration of exogenous 11-cis retinal did not
      rescue retinal morphology or markedly improve ERG responses. CONCLUSIONS: The
      findings provide clarification of reported cone loss of function in Rpe65(-)(/
      )/Nrl(-)(/-) mice, now showing that chromophore absence results in destabilized
      cone outer segments and rapid retinal degeneration. The data support the view
      that rod-dominant retinas do not have a cone-specific mechanism for 11-cis
      retinal synthesis and have potential significance for therapeutic strategies for
      rescue of cone-rich retinal regions affected by disease in the aging human
      population.

PMID- 18326741
TI  - Dorzolamide increases retinal oxygen tension after branch retinal vein occlusion.
AB  - PURPOSE: To study the effect of dorzolamide on the preretinal oxygen tension
      (RPO(2)) in retinal areas affected by experimental branch retinal vein occlusion
      (BRVO) in pigs. METHODS: Experimental BRVO was induced by diathermy close to the
      optic disc. RPO(2) was measured with an oxygen-sensitive electrode 0.5 mm above
      the BRVO-affected area, which was compared to the retinal areas not affected by
      BRVO. In one group of five pigs, RPO(2) was measured at baseline, 1 and 3 hours
      after BRVO, and after intravenous injection of 500 mg dorzolamide. In a second
      group of five pigs, RPO(2) was measured 1 week after the BRVO, both before and
      after intravenous injection of 500 mg dorzolamide. RESULTS: The average baseline
      RPO(2) was 2.64 +/- 0.09 kPa (mean +/- SD). In the BRVO-affected areas, RPO(2)
      decreased significantly (by 0.67 +/- 0.29 and 0.94 +/- 0.13 kPa) at 1 hour and 3
      hours after BRVO induction. In the non-BRVO areas RPO(2) increased significantly
      (by 0.51 +/- 0.14 kPa) 1 hour after BRVO induction, but subsequently decreased
      and reached baseline 3 hours after BRVO induction. One week after BRVO induction,
      RPO(2) was 0.67 +/- 0.29 kPa lower in affected areas when compared with the non
      BRVO areas. In the BRVO-affected areas, dorzolamide increased RPO(2)
      significantly (by 0.36 +/- 0.21 kPa at 3 to 4 hours and by 0.67 +/- 0.40 kPa) 1
      week after BRVO induction. CONCLUSIONS: Retinal hypoxia induced by experimental
      BRVO remained significant 1 week after BRVO. Dorzolamide increased retinal oxygen
      tension in the BRVO-affected areas both at 4 hours and 1 week after experimental
      BRVO in pigs.

PMID- 18326742
TI  - alpha-Aminoadipate induces progenitor cell properties of Muller glia in adult
      mice.
AB  - PURPOSE: Retinal Muller glia in higher vertebrates have been reported to possess
      progenitor cell properties and the ability to generate new neurons after injury.
      This study was conducted to determine the signals that can activate this dormant
      capacity of Muller glia in adult mice, by studying their behavior during
      glutamate stimulation. METHODS: Various concentrations of glutamate and its
      analogue alpha-aminoadipate, which specifically binds Muller glia, were injected
      subretinally in adult mice. Proliferating retinal cells were labeled by
      subretinal injection of 5'-bromo-2'-deoxyuridine (BrdU) followed by
      immunohistochemistry. Muller cell fates were analyzed in retinal sections by
      using double immunolabeling with primary antibodies against Muller and other
      retina-specific cell markers. The effects of glutamate and alpha-aminoadipate
      were also determined in purified Muller cell cultures. RESULTS: Although high
      levels of glutamate induce retinal damage, subtoxic levels of glutamate directly
      stimulate Muller glia to re-enter the cell cycle and induce neurogenesis in vivo
      and in purified Muller cell cultures. alpha-Aminoadipate, which selectively
      target glial cells, also induced expression of progenitor cell markers by Muller
      cells in vitro or stimulated Muller cell migration to the outer nuclear layer
      (ONL) and to differentiate into photoreceptors in vivo. CONCLUSIONS: Mature
      Muller glia in adult mice can be induced to dedifferentiate, migrate, and
      generate new retinal neurons and photoreceptor cells by alpha-aminoadipate or
      glutamate signaling. The results of this study suggest a novel potential strategy
      for treating retinal neurodegeneration, including retinitis pigmentosa and age
      related macular degeneration, without transplanting exogenous cells.

PMID- 18326743
TI  - A pilot study on ocular safety of intravitreal infliximab in a rabbit model.
AB  - PURPOSE: To determine whether infliximab may be used safely as an intraocular
      drug, the ocular safety of intravitreal infliximab in rabbits was studied by
      clinical examination, electroretinography (ERG), and histology in rabbits.
      METHODS: Twelve New Zealand albino rabbits were selected for this study.
      Different infliximab doses, namely 1.0 mg, 1.7 mg, and 3.3 mg in 0.1 mL, were
      injected intravitreally into one eye each of three rabbits. As a control, the
      vehicle solution was injected into the fellow eye of each animal. Eye clinical
      examination and ERG recordings were made before and 2, 6, and 12 weeks after
      injection. Eventually, the rabbits were humanely killed, and the retinas were
      examined by light microscopy. In addition, the elimination half-life of the drug
      in the vitreous was assessed. RESULTS: Slit lamp biomicroscopy, indirect
      funduscopy, and ERG evidenced no significant differences between control and
      infliximab-injected eyes in this rabbit model, at any of the tested doses.
      Histologic examination revealed no retinal abnormality in the rabbits injected
      with 1 mg and 1.7 mg intravitreal infliximab. In two of three eyes injected with
      3.3 mg infliximab, significant edema of the nerve fibers was detected compared
      with the control group. The half-life of the drug was estimated to be 8.5 days.
      CONCLUSIONS: These results indicate that infliximab may be a safe intravitreal
      drug in the rabbit model at a dose of up to 1.7 mg. If proven safe and
      efficacious in further studies, intravitreal injection of infliximab could be
      considered an alternative to systemic administration in selected patients.

PMID- 18326744
TI  - Effect of plasmapheresis on hyperviscosity-related retinopathy and retinal
      hemodynamics in patients with Waldenstrom's macroglobulinemia.
AB  - PURPOSE: Waldenstrom's macroglobulinemia (WM) is characterized by an
      overproduction of immunoglobulin M (IgM), which can lead to a hyperviscosity
      syndrome (HVS) and HVS-related retinopathy. Plasmapheresis is known to reduce
      serum viscosity (SV) and IgM levels. The purpose of this study was to investigate
      the effects of plasmapheresis on HVS-related retinopathy and retinal hemodynamic
      parameters in patients with WM. METHODS: Nine patients with HVS due to WM were
      studied. SV and plasma IgM levels were measured before and after plasmapheresis
      treatment. The patients were evaluated for HVS-related retinopathy, and
      hemodynamic changes in a major temporal retinal vein by laser Doppler, before and
      after plasmapheresis. RESULTS: Plasmapheresis resulted in significant reductions
      in serum IgM (46.5% +/- 18.0%, mean +/- SD; P = 0.0009) and SV (44.7% +/- 17.3%,
      P = 0.002). HVS-related retinopathy improved in all patients after
      plasmapheresis. After treatment, the venous diameter decreased in each patient by
      an average of 15.3% +/- 5.8% (P = 0.0001). A significant (P = 0.0004) 55.2% +/-
      22.5% increase in retinal venous blood speed accompanied the decreases in
      diameter. There was no significant change in the retinal blood flow rate after
      treatment. The percentage decreases in SV in the patients were significantly
      correlated with the percentage decreases in venous blood column diameter (P =
      0.031, R(2) = 0.51). CONCLUSIONS: HVS triggers a distinctive retinopathy with a
      central retinal vein occlusion (CRVO)-like appearance. However, the retinal blood
      flow is not decreased as in CRVO, but remains at normal levels. Plasmapheresis is
      effective in reversing HVS-related retinopathy and in reducing abnormal venous
      dilatation.

PMID- 18326745
TI  - Elevated retina-specific expression of the small heat shock protein, alphaA
      crystallin, is associated with photoreceptor protection in experimental uveitis.
AB  - PURPOSE: During the early phase of experimental autoimmune uveitis (EAU), before
      macrophages infiltrate the retina and uvea, photoreceptor mitochondrial oxidative
      stress, nitration of photoreceptor mitochondrial proteins, and release of
      cytochrome c have been observed. However, no apoptosis has been detected during
      this phase. In this study, alphaA-crystallin upregulation in the retina and its
      antiapoptotic protective role were evaluated in early EAU. METHODS: Gene
      microarrays were first used to identify upregulated genes in retinas with early
      EAU. Among highly upregulated crystallins, alphaA was confirmed by real-time
      polymerase chain reaction and Western blot, and the site of upregulation was
      localized by immunohistochemistry. The association of alphaA-crystallin to
      nitrated cytochrome c and interaction with a procaspase-3 subunit was assayed.
      Photoreceptor apoptosis in alphaA knockout mice was compared with that in wild
      type animals with EAU, by using the terminal transferase dUTP nick-end labeling
      assay and polymerase chain reaction. RESULTS: In early EAU, alphaA-crystallin was
      increased 33-fold, and the site of increase was localized to the photoreceptor
      inner segments. This crystallin suppressed apoptosis by associating with the
      nitrated cytochrome c and p24. The association with nitrated cytochrome c, in
      particular, appeared to be restricted to nitrated cytochrome c, and thus, no
      association of non-nitrated cytochrome c was detected. The knockout mice showed
      signs of EAU development early and showed apoptosis in the retina; no such
      changes were seen in the wild-type control animals. CONCLUSIONS: alphaA
      Crystallin is highly upregulated in the retina during early EAU. This
      upregulation is localized primarily in the photoreceptor inner segments, the site
      of mitochondrial oxidative stress. Further, in early EAU, the photoreceptors
      preferentially use alphaA-crystallin to suppress mitochondrial oxidative stress
      mediated apoptosis.

PMID- 18326746
TI  - Confocal blue reflectance imaging in type 2 idiopathic macular telangiectasia.
AB  - PURPOSE: To report the characteristics of confocal blue reflectance imaging in
      type 2 idiopathic macular telangiectasia (type 2 IMT). METHODS: In a prospective
      observational cross-sectional study, both eyes of 33 patients with type 2 IMT
      were examined by means of fundus biomicroscopy, fundus photography, fluorescein
      angiography, and optical coherence tomography (OCT). Confocal blue reflectance
      (CBR) imaging was performed using a confocal scanning laser ophthalmoscope (HRA2;
      Heidelberg Engineering, Heidelberg, Germany). To compare the results derived from
      different imaging modalities, an analysis was performed using image analysis
      software (Heidelberg Eye Explorer; Heidelberg Engineering). RESULTS: CBR imaging
      revealed a parafoveal area of increased reflectance that was slightly larger than
      the area of hyperfluorescence in late-phase fluorescein angiography. The area
      usually encompassed an oval parafoveal area, but sectors could be spared. A
      parafoveal area of increased CBR was detected in 98% of eyes that showed
      angiographic evidence for type 2 IMT. CONCLUSIONS: CBR imaging is a new,
      noninvasive, and sensitive method that may contribute to differentiate type 2 IMT
      from other diseases. Abnormalities of macular pigment distribution and Muller
      cell pathology may contribute to the phenomenon of increased CBR and thus the
      pathophysiology of type 2 IMT.

PMID- 18326747
TI  - Effects of an anti-VEGF-A monoclonal antibody on laser-induced choroidal
      neovascularization in mice: optimizing methods to quantify vascular changes.
AB  - PURPOSE: The purpose of this study was to evaluate different methods of detecting
      and quantifying experimentally induced choroidal neovascularization (CNV) and
      vascular changes induced on CNV by an anti-VEGF-A monoclonal antibody. METHODS:
      Choroidal neovascularization was induced by 532-nm diode laser in C57BL/6 mice.
      Ten days after the laser, the following methods were used to detect the new
      vessels: high-resolution angiography with fluorescein isothiocyanate-dextran;
      immunohistochemistry with biotinylated isolectin, rabbit anti-NG2, rat anti-CD31,
      rabbit anti-VWF, rat ani-CD105, rabbit anti-collagen IV, rat anti-ICAM-2, rabbit
      anti-desmin, and rat anti-MECA 32; and intravital injection of fluorescein
      labeled Lycopersicon esculentum (tomato) lectin. To verify the validity of these
      staining methods in the quantification of treated CNV, the authors applied the
      most effective of these techniques to three groups of mice after laser induction
      of CNV and treatment with an anti-VEGF full antibody (G6-31). RESULTS:
      Fluorescein isothiocyanate-dextran angiography, rat anti-ICAM-2 immunostaining,
      and tomato lectin intravital injection resulted in the most effective means of
      identifying choroidal neovascularization. A certain amount of nonspecific
      fluorescence was detected in the area of CNV for each METHOD: This fluorescence
      appeared more intense when fluorescein isothiocyanate-dextran was used. Tomato
      lectin injection and rat anti-ICAM-2 immunostaining were the methods that better
      recorded the antiangiogenic drug effect. CONCLUSIONS: Because of easy execution,
      low background fluorescence, and detailed visualization of new vessels,
      intravital injection of tomato lectin followed by a quantification based on
      threshold fluorescence represents the best technique for measuring CNV and the
      vascular changes induced by anti-VEGF-A monoclonal antibody in mice.

PMID- 18326748
TI  - Selective inhibition of angiogenesis in small blood vessels and decrease in
      vessel diameter throughout the vascular tree by triamcinolone acetonide.
AB  - PURPOSE: To quantify the effects of the steroid triamcinolone acetonide (TA) on
      branching morphology within the angiogenic microvascular tree of the
      chorioallantoic membrane (CAM) of quail embryos. METHODS: Increasing
      concentrations of TA (0-16 ng/mL) were applied topically on embryonic day (E) 7
      to the chorioallantoic membrane (CAM) of quail embryos cultured in petri dishes
      and incubated for an additional 24 or 48 hours until fixation. Binary
      (black/white) microscopic images of arterial end points were quantified by
      generational analysis of vessel branching (VESGEN) software to obtain major
      vascular parameters that include vessel diameter (D(v)), fractal dimension
      (D(f)), tortuosity (T(v)), and densities of vessel area, length, number, and
      branch point (A(v), L(v), N(v), and Br(v)). For assessment of specific changes in
      vascular morphology induced by TA, the VESGEN software automatically segmented
      the vascular tree into branching generations (G(1)... G(10)) according to changes
      in vessel diameter and branching. RESULTS: Vessel density decreased significantly
      up to 34% as the function of increasing concentration of TA according to A(v),
      L(v), Br(v), N(v), and D(f). TA selectively inhibited the growth of new, small
      vessels because L(v) decreased from 13.14 +/- 0.61 cm/cm(2) for controls to 8.012
      +/- 0.82 cm/cm(2) at 16 ng TA/mL in smaller branching generations (G(7)-G(10))
      and for N(v) from 473.83 +/- 29.85 cm(-2) to 302.32 +/- 33.09 cm(-2). In
      contrast, vessel diameter (D(v)) decreased throughout the vascular tree (G(1)
      G(10)). CONCLUSIONS: By VESGEN analysis, TA selectively inhibited the
      angiogenesis of smaller blood vessels, but decreased the vessel diameter of all
      vessels within the vascular tree.

PMID- 18326749
TI  - Evidence of widespread retinal dysfunction in patients with stargardt disease and
      morphologically unaffected carrier relatives.
AB  - PURPOSE: To characterize contrast sensitivity (CS) across the visual field for
      two achromatic spatial-temporal frequencies in 21 families with Stargardt disease
      (STGD) and to correlate psychophysical impairment with patterns of change in
      multifocal electroretinography (mfERG). METHODS: Twenty-seven eyes from patients
      with STGD, 16 eyes from asymptomatic relatives, and 44 age-matched control eyes
      were included. Chromatic CS function was assessed by comparing protan, deutan,
      and tritan (Cambridge Color Test; Cambridge Research Systems Ltd., Rochester, UK)
      and anomaloscope measures (IF-2; Roland Consult, Wiesbaden, Germany). Achromatic
      CS measures were obtained with custom-made software in nine locations by using
      randomly interleaved staircases. The first task-low spatial frequency (LSF)
      matched the known frequency-doubling method that is believed to activate the
      magnocellular pathway preferentially. The second included an intermediate spatial
      frequency (ISF, 3.5 cyc/deg). mfERGs (RETIscan; Roland Consult) were also
      obtained. Relatives were screened for ABCA4 mutations by ABCR400 microarray and
      direct sequencing. RESULTS: Central impairment of achromatic and chromatic CS
      (along the three isolation axes) was observed in STGD. LSF and ISF tasks revealed
      significant and widespread dysfunction in patients and their morphologically
      unaffected relatives, 80% of whom were found to be ABCA4 mutation carriers.
      Significant reduction of P1 amplitudes was also observed in both groups.
      CONCLUSIONS: CS function is impaired in patients with STGD at distinct spatial
      temporal frequencies, which, in addition to the color vision deficits, suggests
      dual impairment of the magno- parvocellular pathways. STGD morphologically
      unaffected carriers may show patterns of psychophysical dysfunction that are
      mirrored by abnormal mfERG responses.

PMID- 18326750
TI  - Prevalence and morphology of druse types in the macula and periphery of eyes with
      age-related maculopathy.
AB  - PURPOSE: Macular drusen are hallmarks of age-related maculopathy (ARM), but these
      focal extracellular lesions also appear with age in the peripheral retina. The
      present study was conducted to determine regional differences in morphology that
      contribute to the higher vulnerability of the macula to advanced disease.
      METHODS: Drusen from the macula (n = 133) and periphery (n = 282) were isolated
      and concentrated from nine ARM-affected eyes. A semiquantitative light
      microscopic evaluation of 1-mum-thick sections included 12 parameters. RESULTS:
      Significant differences were found between the macula and periphery in ease of
      isolation, distribution of druse type, composition qualities, and substructures.
      On harvesting, macular drusen were friable, with liquefied or crystallized
      contents. Peripheral drusen were resilient and never crystallized. On
      examination, soft drusen appeared in the macula only, had homogeneous content
      without significant substructures, and had abundant basal laminar deposits
      (BlamD). Several substructures, previously postulated as signatures of druse
      biogenesis, were found primarily in hard drusen. Specific to hard drusen, which
      appeared everywhere, were central subregions and reduced RPE coverage. Macular
      hard drusen with a rich substructure profile differed from primarily homogeneous
      peripheral hard drusen. Compound drusen, found in the periphery only, exhibited a
      composition profile that was not intermediate between hard and soft. CONCLUSIONS:
      The data confirm regional differences in druse morphology, composition, and
      physical properties, most likely based on different formative mechanisms that may
      contribute to macular susceptibility for ARM progression. Two other reasons that
      only the macula is at high risk despite having relatively few drusen are the
      exclusive presence of soft drusen and the abundant BlamD in this region.

PMID- 18326751
TI  - N-(4-hydroxyphenyl) retinamide augments laser-induced choroidal
      neovascularization in mice.
AB  - PURPOSE: To evaluate the effect of N-4-hydroxyphenyl retinamide (4-HPR) on
      experimental laser-induced choroidal neovascularization (CNV) and on the
      expression and secretion of relevant growth factors by cultured human retinal
      pigment epithelial (RPE) cells. METHODS: CNV was induced by laser
      photocoagulation in C57BL/6 mice. 4-HPR (0.2 or 1 mg) or vehicle, was injected
      intraperitoneally twice daily for 14 days. Plasma and tissue levels of 4-HPR were
      measured by HPLC. CNV was evaluated by fluorescein angiography, histology, and
      quantitative confocal analysis of isolectin B4 histochemistry on days 7 and 14.
      Induction of apoptosis and expression and secretion of growth factors was studied
      in 4-HPR-treated RPE cultures. RESULTS: Mice treated with 4-HPR exhibited time-
      and dose-dependent increases in plasma and tissue 4-HPR levels. CNV lesions
      showed increased volume with increased vascular leakage and contained fewer
      lesion-associated RPE in treated versus untreated mice. Treatment of nonpolarized
      RPE cultures with 4-HPR in the presence of serum resulted in RPE apoptosis;
      however, apoptosis was minimal in similarly treated highly polarized RPE.
      Treatment of RPE cells with 4-HPR resulted in the upregulation of VEGF-A and -C
      (P < 0.05) and Ang-1 (P < 0.01) mRNA and increased secretion of VEGF-A and -C (P
      < 0.05), whereas pigment epithelium-derived growth factor (PEDF) and
      thrombospondin (TSP)-1 mRNA expression and secretion were downregulated (P <
      0.05). CONCLUSIONS: 4-HPR increases lesion size and leakage in laser-induced CNV
      and is associated with the upregulation of key proangiogenic factors and the
      downregulation of antiangiogenic factors. Consistent with the preferential loss
      of RPE in CNV lesions in vivo, 4-HPR induces apoptosis of nonpolarized RPE in the
      presence of serum.

PMID- 18326752
TI  - Expression of ZnT and ZIP zinc transporters in the human RPE and their regulation
      by neurotrophic factors.
AB  - PURPOSE: Zinc is an essential cofactor for normal cell function. Altered
      expression and function of zinc transporters may contribute to the pathogenesis
      of neurodegenerative disorders including macular degeneration. The expression and
      regulation of zinc transporters in the RPE and the toxicity of zinc to these
      cells were examined. METHODS: Zinc transporters were identified in a human RPE
      cell line, ARPE19, using a 28K human array, and their expression was confirmed by
      PCR, immunocytochemistry, and Western blot analysis in primary human RPE cultures
      and ARPE19. Zinc toxicity to ARPE19 was determined using monotetrazolium,
      propidium iodide, and TUNEL assays, and Zn(2+) uptake was visualized with Zinquin
      ethyl ester. The effect of various growth factors on zinc transporter expression
      also was examined. RESULTS: Transcripts for 20 of 23 zinc transporters are
      expressed in fetal human RPE, 16 of 23 in adult human RPE, and 21 of 23 in
      ARPE19. Zn transporter proteins were also detected in ARPE19. ZnT5 expression was
      not observed, whereas ZnT6, ZIP1, and ZIP13 were the most abundantly expressed in
      all RPE samples. The addition of low concentrations of Zn(2+) to cultures
      resulted in a dose-dependent increase in intracellular Zn(2+) content in ARPE19,
      and >30 nM Zn(2+) induced necrosis with an LC(50) of 117.4 nM. Brain-derived
      neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic
      factor (GDNF), and pigment epithelial-derived neurotrophic factor (PEDF)
      increased ZIP2 expression, GDNF and PEDF increased ZnT2 expression, and PEDF
      increased ZnT3 and ZnT8 expression. These neurotrophic factors also promoted
      Zn(2+) uptake in the RPE. CONCLUSIONS: The array of zinc transporters expressed
      by the RPE may play a key role in zinc homeostasis in the retina and in ocular
      health and diseases.

PMID- 18326753
TI  - Advanced glycation of fibronectin impairs vascular repair by endothelial
      progenitor cells: implications for vasodegeneration in diabetic retinopathy.
AB  - PURPOSE: Vascular repair by marrow-derived endothelial progenitor cells (EPCs) is
      impaired during diabetes, although the precise mechanism of this dysfunction
      remains unknown. The hypothesis for the study was that progressive basement
      membrane (BM) modification by advanced glycation end products (AGEs) contributes
      to impairment of EPC reparative function after diabetes-related endothelial
      injury. METHODS: EPCs isolated from peripheral blood were characterized by
      immunocytochemistry and flow cytometry. EPC interactions on native or AGE
      modified fibronectin (AGE-FN) were studied for attachment and spreading, whereas
      chemotaxis to SDF-1 was assessed with the Dunn chamber assay. In addition,
      photoreactive agent-treated monolayers of retinal microvascular endothelial cells
      (RMECs) produced circumscribed areas of apoptosis and the ability of EPCs to
      "endothelialize" these wounds was evaluated. RESULTS: EPC attachment and
      spreading on AGE-FN was reduced compared with control cells (P < 0.05-0.01) but
      was significantly restored by pretreatment with Arg-Gly-Asp (RGD). Chemotaxis of
      EPCs was abolished on AGE-FN but was reversed by treatment with exogenous RGD. On
      wounded RMEC monolayers, EPCs showed clustering at the wound site, compared with
      untreated regions (P < 0.001); AGE-FN significantly reduced this targeting
      response (P < 0.05). RGD supplementation enhanced EPC incorporation in the
      monolayer, as determined by EPC participation in tight junction formation and
      restoration of transendothelial electric resistance (TEER). CONCLUSIONS: AGE
      modification of vascular substrates impairs EPC adhesion, spreading, and
      migration; and alteration of the RGD integrin recognition motif plays a key role
      in these responses. The presence of AGE adducts on BM compromises repair by EPC
      with implications for vasodegeneration during diabetic microvasculopathy.

PMID- 18326754
TI  - Role of cytochrome P450 2C epoxygenases in hypoxia-induced cell migration and
      angiogenesis in retinal endothelial cells.
AB  - PURPOSE: Cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids
      (EETs) elicit cell proliferation and promote angiogenesis. The aim of this study
      was to determine the expression of CYP epoxygenases in the bovine retina and the
      potential role of EETs in hypoxia-induced angiogenesis in bovine retinal
      endothelial cells. METHODS: Bovine retinal endothelial cells were cultured under
      normoxic (21% O(2)) or hypoxic (1% O(2)) conditions, and CYP2C expression was
      determined by Western blot analysis. The effect of hypoxia on EET levels was
      determined by LC-MS/MS. Cell migration (Transwell filter assays) and endothelial
      cell tube formation (on basement membrane matrix) were assessed in vitro in the
      absence and presence of pharmacologic inhibitors and CYP2C antisense
      oligonucleotides. RESULTS: Bovine retinal endothelial cells expressed CYP2C
      protein in culture and generated detectable levels of EETs under basal
      conditions. Hypoxia (6-48 hours) enhanced CYP2C protein expression (2-fold) and
      EET formation (1.5-fold). Moreover, endothelial cells preexposed to hypoxia
      demonstrated an increase in serum-induced cell migration that was sensitive to
      the CYP2C inhibitors sulfaphenazole and MS-PPOH and the EET antagonist 14,15
      epoxyeicosa-5(Z)-enoic acid. Furthermore, preventing the hypoxia-induced
      expression of CYP2C (antisense oligonucleotides) suppressed hypoxia-induced cell
      migration. In an in vitro angiogenesis model, the preexposure of endothelial
      cells to hypoxia increased CYP2C expression and enhanced endothelial tube
      formation, which was blocked by the EET antagonist and by the CYP2C antisense
      oligonucleotides. CONCLUSIONS: Taken together, these data indicate that CYP2C
      derived EETs are implicated in angiogenesis by retinal endothelial cells,
      especially under hypoxic conditions.

PMID- 18326755
TI  - Inducible expression of cre recombinase in the retinal pigmented epithelium.
AB  - PURPOSE: The retinal pigmented epithelium (RPE) expresses many genes that play
      important roles in the support and maintenance of photoreceptors. The present
      study was conducted to develop a system amenable to the dissection of the
      temporal function of these genes, specifically within RPE cells. Transgenic mice
      were generated and characterized in which the expression of Cre recombinase could
      be specifically induced within the RPE. METHODS: Transgenic mice carrying the
      human vitelliform macular dystrophy-2 (VMD2) promoter (P(VMD2))-directed reverse
      tetracycline-dependent transactivator (rtTA) and the tetracycline-responsive
      element (TRE)-directed cre were generated. Inducible Cre expression was achieved
      by feeding doxycycline to these mice and was characterized by using a Cre
      activatable lacZ reporter mouse strain (R26R). RESULTS: A beta-galactosidase
      assay of rtTA/Cre-R26R mice demonstrated that the basal level of Cre expression
      without doxycycline induction was negligible. Addition of doxycycline led to
      induction of RPE-specific Cre expression/function at least from embryonic day 9
      to postnatal day 60. The highest induction occurred at approximately postnatal
      day 4. As measured by ERG and histology, retinal function and morphology were
      normal in 10-month-old rtTA/Cre mice that were treated with doxycycline at
      weaning age. CONCLUSIONS: Transgenic mice were generated that express Cre
      recombinase in the RPE in an inducible fashion. These mice will be useful for
      studies of the RPE-specific role of genes that are expressed in the RPE as well
      as other cells, particularly for avoiding embryonic lethality and dissecting the
      function of genes that play dual roles in development and adulthood.

PMID- 18326756
TI  - Saffron supplement maintains morphology and function after exposure to damaging
      light in mammalian retina.
AB  - PURPOSE: To test whether the saffron extract (Crocus sativus L.) given as a
      dietary supplement counteracts the effects of continuous light exposure in the
      albino rat retina. METHODS: Three experimental groups of Sprague-Dawley rats were
      used. Experimental animals were prefed either saffron or beta-carotene (1 mg
      extract/kg/d) before they were exposed to bright continuous light (BCL) for 24
      hours. Flash electroretinograms (fERGs) were recorded in control and treated rats
      the day before and 1 week after light exposure. At the end of the second
      recording session, the animals were killed and the retinas were quickly removed,
      fixed, cryosectioned, and labeled so that the thickness of the outer nuclear
      layer (ONL) could be analyzed. Changes in protein level and cellular localization
      of fibroblast growth factor (FGF)2 were determined by Western blot analysis and
      retinal immunohistochemistry, respectively. In a second series of experiments,
      rats were killed at the end of light exposure, and the amount of apoptotic
      figures in the ONL was assessed by terminal transferase-mediated deoxyuridine
      triphosphate (d-UTP)-biotin nick-end labeling (TUNEL). BCL induced DNA
      fragmentation, characteristic of dying cells, almost exclusively in the
      photoreceptor layer. The rate of photoreceptor death induced by BCL is expressed
      as the frequency of TUNEL-positive profiles per millimeter. RESULTS: The
      photoreceptor layer was largely preserved in saffron-treated animals because it
      was the fERG response. In addition, the rate of photoreceptor death induced by
      BCL appeared drastically reduced in treated animals. In beta-carotene prefeeding
      experiments, morphologic analysis showed preservation of the ONL similar to that
      obtained with saffron prefeeding, whereas the fERG response was unrecordable.
      Western blot analysis showed that exposure to light induced a strong upregulation
      of FGF2 in control and beta-carotene-treated rats, but s no change was noted in
      saffron-treated rats. CONCLUSIONS: These results show that saffron may protect
      photoreceptors from retinal stress, maintaining both morphology and function and
      probably acting as a regulator of programmed cell death.

PMID- 18326757
TI  - Early activation of inflammation- and immune response-related genes after
      experimental detachment of the porcine retina.
AB  - PURPOSE: To determine early alterations in retinal gene expression in a porcine
      model of rhegmatogenous retinal detachment. METHODS: Local detachment was created
      in eyes of adult pigs by subretinal application of sodium hyaluronate. The gene
      expression in control tissues and retinas detached for 24 hours was analyzed with
      a pig genome microarray. Genes with at least three-fold expression changes were
      detected in the detached retina and in the attached retinal tissue surrounding
      the local detachment in situ. Structural alterations of the retina were examined
      by light and electron microscopy. RESULTS: Identified were 85 genes that were
      upregulated and 7 that were downregulated in the detached retina. Twenty-eight
      genes were identified as upregulated in the nondetached retina of the surgical
      eyes. The genes upregulated in detached retinas were related to inflammation and
      immune responses (n = 52), antioxidants and metal homeostasis (n = 7),
      intracellular proteolysis (n = 6), and blood coagulation/fibrinolysis (n = 4).
      The upregulation of at least 15 interferon-stimulated genes indicates elevated
      interferon levels after detachment. Gene expression of blue-sensitive opsin was
      not detectable in the detached retinal tissue, suggesting an early reduction in
      phototransduction, especially in blue cones. Electron microscopy revealed an
      accumulation of microglial cells in the inner retinal tissue and of
      polymorphonuclear leukocytes in the vessels of detached and peridetached retinas.
      CONCLUSIONS: Differentially expressed genes in the retina early after
      experimental detachment are mainly related to inflammation and immune responses,
      intracellular proteolysis, and protection against oxidative stress. A local
      immune and inflammatory response may represent a major causative factor for
      reactive changes in the retina after detachment. The inflammatory response is not
      restricted to the detached retina but is also observed in the nondetached retina;
      this response may underlie functional changes in these regions described in human
      subjects.

PMID- 18326758
TI  - Implication of S-adenosylhomocysteine hydrolase in inhibition of TNF-alpha- and
      IL-1beta-induced expression of inflammatory mediators by AICAR in RPE cells.
AB  - PURPOSE: AMP-activated protein kinase (AMPK) has been suggested to be a novel
      signaling pathway in regulating inflammation. The role of AMPK in retinal pigment
      epithelial cell inflammatory response is addressed using AMPK activator 5
      aminoimidazole-4-carboxamide riboside (AICAR). METHODS: Protein expression and
      activation of signaling molecules were detected by immunoblotting. Cytokines were
      determined by ELISA kits. AMPKalpha expression was knockdown by siRNAs. RESULTS:
      AICAR inhibited tumor necrosis factor (TNF)-alpha- or interleukin (IL)-1beta
      induced production of IL-6, IL-8, and monocyte chemotactic protein (MCP)-1 and of
      intercellular adhesion molecule (ICAM)-1 expression in human RPE cells. The
      inhibitory effect on cytokine production and ICAM-1 expression persisted in the
      RPE cells in which AMPK was knocked down by AMPK siRNA. Moreover, an adenosine
      kinase inhibitor 5'-iodotubercidin, which effectively abolished AMPK activation
      caused by AICAR, did not reverse the anti-inflammatory effect of AICAR. In
      comparison, anti-inflammatory effects of AICAR were mimicked by adenosine but not
      inosine, the metabolites of AICAR. Finally, with the exception of TNF-alpha
      induced IL-6 production, adenosine dialdehyde, an inhibitor of S
      adenosylhomocysteine hydrolase, was found to block cytokine production and ICAM-1
      expression. CONCLUSIONS: Regardless of the ability of AICAR to activate AMPK, the
      inhibitory effects of AICAR on cytokine production and ICAM-1 expression were not
      associated with AMPK. The mechanism of AICAR inhibition may be attributed to the
      interference of adenosylmethionine-dependent methylation.

PMID- 18326759
TI  - BDNF increases survival of retinal dopaminergic neurons after prenatal
      compromise.
AB  - PURPOSE: Chronic placental insufficiency (CPI) severe enough to cause growth
      restriction (GR) results in alterations to the retina, including a reduction in
      tyrosine hydroxylase immunoreactive (TH-IR)-dopaminergic amacrine cells. Brain
      derived neurotrophic factor (BDNF) plays a role in the development of the retinal
      dopaminergic network and may therefore be an appropriate therapy for restoring
      dopaminergic cells after prenatal compromise. This study was conducted (1) to
      establish whether BDNF and its receptor NTRK2 (Trk B) are altered in the retina
      after CPI and (2) to explore the potential of BDNF to enhance dopaminergic cell
      survival in organotypic retinal cultures from prenatally compromised animals.
      METHODS: CPI was induced in pregnant guinea pigs at 30 days' gestation (dg; term,
      approximately 67 dg) via unilateral ligation of the uterine artery. Fetuses were
      euthanatized at 60 dg and the retinas prepared for enzyme-linked immunosorbent
      assay (ELISA) analysis of BDNF protein levels and for immunohistochemistry to
      localize BDNF and NTRK2. Organotypic cultures of retinas from GR and control
      fetuses at 50 to 52 dg were treated with BDNF, and dopaminergic amacrine cells
      counts were assessed. RESULTS: Retinal BDNF protein levels and the intensity of
      BDNF-immunoreactivity (IR) in the ganglion cell layer were reduced (P < 0.05) in
      GR fetuses compared with control fetuses. Addition of BDNF to organotypic
      cultures increased (P < 0.05) the survival and neurite growth of dopaminergic
      neurons from both control and GR fetuses. CONCLUSIONS: Alterations to BDNF levels
      may underlie reductions in dopaminergic amacrine cells observed after CPI. The
      addition of BDNF has the potential to increase survival and neurite growth of
      dopaminergic amacrine cells.

PMID- 18326760
TI  - Firm but gentle: learning to handle with care.

PMID- 18326761
TI  - Animal handling as an integrated component of animal and veterinary science
      programs at the University of Queensland.
AB  - Students in animal science and veterinary science at the University of Queensland
      (UQ) have similar introductory courses in animal handling in year 1 of their
      degree programs. Veterinary students take animal-handling instruction in farm and
      companion animals, whereas animal science students are instructed in handling
      farm animals, horses, and rodents. Veterinary students are introduced to rodents,
      and animal science students to dogs and cats, in subsequent years of the
      curriculum. Both cohorts receive additional training, with clinical emphasis for
      veterinary students in years 3, 4, and 5 of their five-year curriculum. The
      introductory course is well received by students; both student cohorts appreciate
      the opportunity provided and the effort that goes into the animal-handling
      classes. Undergraduates realize that acquiring animal-handling skills will
      increase their proficiency in their subsequent careers; veterinary graduates
      recognize that their handling prowess will give their clients confidence in their
      abilities. Most clients cannot judge the competence of a veterinarian's diagnosis
      or treatment but will judge their ability based on their handling skills. Ongoing
      practice allows students to become competent in animal handling.

PMID- 18326762
TI  - Large-animal handling at the Colorado State University College of Veterinary
      Medicine.
AB  - Colleges of veterinary medicine face many challenges in teaching the handling of
      large animals. It is imperative that students be taught how to manage large
      animals, however, not only for their safety but for that of their clients and of
      the animals themselves. Confident, safe, and efficient handling can improve job
      satisfaction and may encourage students to enter large-animal practice. There is
      wide variation in the large-animal-handling components of US veterinary
      curricula.

PMID- 18326763
TI  - Animal-handling teaching at the Royal (Dick) School of Veterinary Studies,
      University of Edinburgh.
AB  - This article describes the teaching of animal handling at the Royal (Dick) School
      of Veterinary Studies, University of Edinburgh, as part of an animal husbandry
      course during the first two years of the veterinary curriculum. Basic methods of
      handling and restraint appropriate for the wide range of animal species that
      might be encountered in veterinary practice are demonstrated in practical
      handling classes. Students are given opportunities to practice the techniques
      under supervision. Additional handling experience is available during extramural
      studies in animal husbandry at a variety of establishments. Students are formally
      examined on their ability to handle and restrain animals, and each is required to
      reach a threshold degree of competence before progressing to the clinical years.

PMID- 18326764
TI  - Practical animal-handling classes at University College Dublin.
AB  - The first two years of the veterinary program at University College Dublin (UCD)
      include two modules whereby students gain experience in basic animal handling.
      Practical Animal Husbandry uses both lectures and animal handling classes aimed
      at teaching students to approach, restrain, and carry out routine husbandry
      procedures on food-producing and companion animals humanely and competently and
      to be aware of the risks to human health of inappropriate animal approach and
      handling. Staff and students are given lists of animal-handling competencies
      designed to ensure that students attain relevant handling skills for beef and
      dairy cattle, pigs, horses, sheep, cats, dogs, and exotics (e.g., rabbits, guinea
      pigs). Students are allotted up to 12 weeks of Farm and Companion Animal
      Experience, an extramural (EMS) activity, according to their prior experience;
      the objectives are to become proficient in the handling and management of animals
      and to develop an understanding of the key husbandry factors in food-production
      systems (milk, beef, lamb, pork) at the farm level. Students are assessed in
      practical examinations at the end of the second year and cannot progress until
      they have achieved the required competence. In addition to the pedagogic
      strategies, special consideration is given to the welfare of the animals used in
      teaching practicals and to the health and safety of teaching staff and students.

PMID- 18326765
TI  - Training in animal handling for veterinary students at Charles Sturt University,
      Australia.
AB  - Charles Sturt University in New South Wales, Australia, is responding to a
      national need for veterinarians with the skills and attributes to fulfill roles
      in rural practice and the large-animal industries. Rural practitioners must
      competently and confidently handle a range of large animals if they are to build
      a relationship of mutual trust with clients and deliver effective animal-health
      services. Training in animal handling begins in the first year of the course with
      highly structured small-group practical classes involving cattle, horses, sheep,
      dogs, cats, pigs, poultry, and laboratory animals (rats and mice). Other
      experiences with animals in the first three years build on basic animal-handling
      skills while performing other veterinary activities. Students who provide
      documented evidence of prior animal-handling experiences are admitted, and
      learning and teaching strategies aim to enhance skills and knowledge. Rigorous
      examinations use a competency-based approach prior to extramural placements on
      farms and in veterinary practices. A continuing process of evaluation, review,
      and refinement will ensure continual improvement and graduate veterinarians with
      strong skills in animal handling.

PMID- 18326766
TI  - Student training in large-animal handling at the School of Veterinary and
      Biomedical Sciences, Murdoch University, Australia.
AB  - The ability to handle animals safely, competently, and with confidence is an
      essential skill for veterinarians. Poor animal-handling skills are likely to
      compromise credibility, occupational health and safety, and animal welfare. In
      the five-year veterinary science degree at Murdoch University, animal handling is
      taught in a prerequisite unit in the second semester of the second year. From
      2008, however, this unit will be taught in the first year of the five-year
      course. Students are taught to handle sheep, cattle, pigs, and horses safely and
      competently. Each student receives 30 hours of formal practical instruction.
      Animal-to-student ratios are 2:1, and staff-to-student ratios vary from 1:8
      (sheep, cattle, horses) to 1:17 (pigs). Students must pass the practical exam to
      proceed into third year. Additional experience with animals is gained during
      third year (14 hours of practical instruction with sheep, goats, pigs, and
      cattle) and during the 5 weeks and 2 days of vacation farm experience during the
      second and third years. In the fourth and fifth years, students consolidate their
      handling experience with sheep (including rams), goats, pigs, cattle (including
      bulls), horses (including stallions), and alpacas. As a result, students are able
      to handle and restrain client animals with confidence. There is no formal course
      in small-animal handling at Murdoch University. Factors that have enhanced the
      success of the large-animal handling program include purpose-built on-campus
      facilities. Inadequate resources (time, facilities, and animals) remain the main
      impediment to effective learning, further compounded by the increasing tendency
      of university administrators to make decisions based on economic expediency
      rather than educational benefit.

PMID- 18326767
TI  - Teaching animal handling to veterinary students at Massey University, New
      Zealand.
AB  - The veterinary program at the Institute of Veterinary, Animal and Biomedical
      Sciences, Massey University, New Zealand, is 4.5 years long. Animal handling and
      restraint are taught to first-year veterinary students via lectures and practical
      sessions. Students are taught to catch, restrain, and hold the five important
      domesticated species (horses, cattle, sheep, dogs, and cats) in a series of five
      practical sessions, each lasting about three hours. Safety is emphasized.
      Students are taught in groups of 10-12, and generally the tutors demonstrate the
      various techniques of restraint and then supervise students as they carry them
      out. Each student's ability to handle and restrain each species is evaluated.
      Students must be considered proficient with each species before being allowed to
      handle animals in clinics. Students are taught how to catch and restrain birds,
      laboratory animals, farm deer, and pigs later in the program.

PMID- 18326768
TI  - Learning and teaching animal handling at the University of Sydney's Faculty of
      Veterinary Science.
AB  - Handling animals in veterinary contexts can present unique challenges that are
      difficult to anticipate. Skillful handling of animals in health and disease
      enhances client and patient relations, while inappropriate handling affects
      diagnostic parameters and is detrimental to a compromised patient's ability to
      cope. This article describes animal-handling opportunities in the veterinary
      curriculum at the University of Sydney, Australia, with an overview of the core
      handling skills required at graduation.

PMID- 18326769
TI  - Two students' reflections on their training in animal handling at the University
      of Sydney.
AB  - Basic animal-handling skills are essential for any veterinary practitioner to
      work safely and confidently. This short article offers the reflections of two
      students who undertook training in basic animal-handling skills at the University
      of Sydney as part of the Veterinary Science degree program. Several students
      attending their final-year clinical rotation at the University of Sydney were
      asked to informally assess their own basic animal-handling skills at the
      beginning of the course and in their final year. These perceptions were matched
      to career choices and demonstrated the positive effect of skills training in
      career choice. As with any skills-based training program, limitations such as
      time and finances place restrictions on student learning, and there is a
      continual need to assess and, where possible, make improvements to the program.

PMID- 18326770
TI  - Development of a model animal welfare act curriculum.
AB  - Animal-welfare issues are often controversial and frequently have an emotional
      component. Veterinarians have extensive knowledge, experience, and scientific
      perspective and are arguably the professionals best suited to advise and develop
      recommendations on animal welfare. The development of an Animal Welfare Act (AWA)
      teaching module is a first step toward educating veterinary students about animal
      welfare. This article presents the current development status of this curriculum
      project, which is intended to be a valuable addition to the evolving veterinary
      education on animal welfare.

PMID- 18326771
TI  - Veterinary education as leader: which alternatives?
AB  - This article suggests that veterinary medicine has a leadership role to play in
      our society on ethical matters involving non-human animals. The article contrasts
      two trends within veterinary medicine; the first trend is a continuation of the
      avowedly utilitarian attitude toward non-humans that has its roots in Western
      veterinary medicine's eighteenth-century origins, and the second is the implicit
      view in veterinary practice that animals matter in and of themselves. Using the
      idea of alternatives in research and teaching, the article suggests that, in the
      years to come, veterinary medicine's answers to the relationships of these two
      trends will shape not only the soul of veterinary medicine, veterinary education,
      and the veterinary profession but, just as importantly, the larger society and
      culture themselves. This text is based on the keynote address delivered at the
      AAVMC Education Symposium in Washington, DC, on March 9, 2006, under the title
      "Ethical Issues Impacting Animal Use in Veterinary Medical Teaching."

PMID- 18326772
TI  - Animals in veterinary medical teaching: compliance and regulatory issues, the US
      perspective.
AB  - Veterinary schools in the United States are regulated as research facilities
      under the federal Animal Welfare Act by Animal Care (AC), a division of the
      USDA's Animal and Plant Health Inspection Service (APHIS). The schools are
      inspected at least annually by AC inspectors, who are all veterinarians. In a
      recent poll, these inspectors identified several areas that have caused
      compliance problems for veterinary schools. In addition, several emerging issues
      also appear to be posing potential regulatory problems as societal expectations
      and ethical considerations change.

PMID- 18326773
TI  - Teaching surgery to the veterinary novice: the Ohio State University experience.
AB  - Surgical training in veterinary medicine has evolved rapidly over the past
      several decades. Catalysts for change include pressure from concerned students
      and the public to reduce the use of live animals in teaching; less-than-effective
      preparation of students for live surgery experience; an overall reduction in
      faculty time and effort devoted to skills training; college budgetary
      reallocations mandating reductions in expensive group laboratory experiences; and
      more specialized case-load patterns in clinical rotations, which have reduced
      students' exposure to common surgical conditions. In response to these trends,
      methods for surgery educators to reduce, refine, and replace live animals in
      surgery training courses at veterinary schools have received broad attention.
      When these methods are used effectively in a curriculum, it is no longer
      necessary to sacrifice animals for adequate student training. This article
      describes a successful and ethical surgical training program used at the Ohio
      State University College of Veterinary Medicine (OSU-CVM). This program provides
      early exposure to skills training using surgical simulators and auto-tutorials,
      ensures that basic skills are mastered before students are exposed to cadaver
      practice, and requires application of model-based skills to cadavers, with final
      matriculation to intensive exposure to multiple live-animal procedures via a
      collaborative surgery program with a local shelter.

PMID- 18326774
TI  - Obstacles associated with organizational change.
AB  - This article briefly explores one view of the change process, discusses obstacles
      to change, the means to deal with these obstacles, and describes change
      principles and specific examples of change strategies that commonly work.

PMID- 18326775
TI  - Animal welfare education in Turkey.
AB  - Veterinary medical education in Turkey began in 1842 and is now offered by 17
      universities. Since 1895, topics related to animal welfare have been covered as
      part of the curriculum in courses titled Deontology, Health Inspection, and Laws
      of Veterinary Medicine. During the 2004/2005 academic year, for the first time,
      animal welfare was included as a separate course as part of the curriculum in two
      veterinary faculties. As a result of curriculum adjustment efforts at both
      national and international levels, the animal-welfare course is now expected to
      be required for all veterinary students in Turkey. This study reports on the
      development of animal-welfare curricula in veterinary medical education in Turkey
      and describes the historical events from which the appreciation of it arose.

PMID- 18326776
TI  - Admissions procedures at the University of Veterinary Medicine Vienna, Austria.
AB  - RATIONALE FOR THIS STUDY: The admission procedure implemented in fall 2005 in
      consequence of new laws passed in summer 2005 is described and evaluated. The
      general set-up, the underlying considerations, and the changes resulting from the
      establishment of this procedure are presented. METHODOLOGY: Admission variables
      and demographic information (sex, age, nationality) for 172 students who entered
      their first academic year at the University of Veterinary Medicine Vienna (VUW)
      and their academic performance measured according to their results in the three
      first-year examinations (successful versus unsuccessful) were assessed. Logistic
      regression was used to examine the relationship between predictor and outcome.
      RESULTS: Regression analysis indicates that Austrian students were more likely to
      be unsuccessful than German students (R(2) = 0.366, p < 0.001). Previous school
      performance was the best predictor for success in the Austrian cohort (R(2) =
      0.196; p < 0.001), whereas the personal interview scores provided the best
      predictor in the German cohort (R(2) = 0.122; p < 0.05). CONCLUSION: This study
      supports our existing selection practices relating to cognitive and non-cognitive
      skills. The number of strugglers may be reduced on the basis of an admissions
      procedure, but struggling may not be excluded by the existing selection
      practices, which do not assess a specific threshold but are related to a score
      ranking system and a predefined number of available openings in the program.

PMID- 18326777
TI  - Veterinary students and their reported academic and personal experiences during
      the first year of veterinary school.
AB  - Veterinary students completed an online survey regarding personal and academic
      concerns they experienced during their first year of veterinary school.
      Quantitative results showed a high degree of stress and anxiety among the study
      participants as well as concerns about time management and study skills.
      Quantitative analysis using chi-square tests revealed significant associations
      between concerns about study skills and the independent variables of relationship
      status and time since obtaining an undergraduate degree. Results of a thematic
      analysis undertaken with the qualitative data provide further insight into first
      year experiences, indicating concerns about the intensity of the program and
      especially about time commitment, the amount of information students were
      expected to learn, and the amount of material they were expected to memorize.
      Another theme revealed that students did not feel academically prepared for some
      of their first-year courses, which led to their not liking those courses for
      which they lacked appropriate groundwork. Other themes highlighted the students'
      desire for more clinically relevant experiences during their first year as well
      as surprises regarding the maturity level of classmates and the level of support
      offered by professors. Given the results of this study, suggestions for
      counselors and others who work with veterinary students are provided.

PMID- 18326778
TI  - Helping students learn veterinary physiology through the use of concept maps.
AB  - Concept maps have become a ubiquitous tool in education in the last 20 years and
      are used extensively to teach scientific concepts. A concept map is a tool
      learners can use to organize information about a topic in terms of key concepts
      and the relationships among them. As a graphical representation, the map provides
      an overall picture of a particular concept or topic. This article describes how
      we have used concept maps to teach physiology to veterinary medical and
      veterinary technician students enrolled in our on-campus and distance-learning
      programs.

PMID- 18326779
TI  - Integrating molecular biology into the veterinary curriculum.
AB  - The modern discipline of molecular biology is gaining increasing relevance in the
      field of veterinary medicine. This trend must be reflected in the curriculum if
      veterinarians are to capitalize on opportunities arising from this field and
      direct its development toward their own goals as a profession. This review
      outlines current applications of molecular-based technologies that are relevant
      to the veterinary profession. In addition, the current techniques and
      technologies employed within the field of molecular biology are discussed.
      Difficulties associated with teaching a subject such as molecular biology within
      a veterinary curriculum can be alleviated by effectively integrating molecular
      topics throughout the curriculum, pitching the subject at an appropriate depth,
      and employing varied teaching methods throughout.

PMID- 18326780
TI  - Incorporating an audience response system into veterinary dermatology lectures:
      effect on student knowledge retention and satisfaction.
AB  - Veterinary educators are charged with delivering large amounts of information to
      adult students, who benefit from a more interactive learning environment than is
      often achieved through didactic lectures. Audience response systems (ARS) with
      wireless keypad technology facilitate interactive learning and have been used
      successfully in the education of health professionals. The objectives of this
      pilot study were to determine the effect of an ARS on the knowledge retention of
      veterinary dermatology students and to survey student attitudes concerning its
      use. A cohort-controlled trial was conducted to evaluate the potential benefits
      of ARS for short-term and long-term knowledge retention. Students also
      participated in four hours of student-directed case simulations using ARS
      technology. Students were surveyed regarding opinions on the use of the ARS. The
      mean short-term knowledge-retention test scores of groups A (ARS+) and B (ARS-)
      were 81% and 78%, respectively. The mean long-term knowledge-retention test
      scores of groups A and B were 54% and 55%, respectively. The differences between
      groups were not significant for either time period (p = 0.32, p = 0.77). Although
      benefits to short-term and long-term knowledge retention were not detected in
      this pilot study, all students responding to the survey perceived a benefit and
      supported the use of ARS in the clinical veterinary curriculum. ARS technology
      provides a tool for lecturers to create an interactive learning environment well
      suited for teaching veterinary dermatology.

PMID- 18326781
TI  - Business education in veterinary schools: the potential role of the Veterinary
      Business Management Association.
AB  - Studies have indicated the importance of business education in improving the
      income level attained by veterinarians and the quality of service they provide.
      The Veterinary Business Management Association (VBMA), a national organization of
      veterinary students, has the potential to augment veterinary curricula by
      providing additional education to help ensure professional success. Local
      chapters at 27 of the 28 veterinary colleges in the United States (as of 2007)
      supplement the curriculum by focusing on business topics. A national governing
      board oversees the chapters, helping to ensure that high-quality educational
      programs are conducted and providing a conduit for communication.

PMID- 18326782
TI  - An alumni survey to assess self-reported career preparation attained at a US
      veterinary school.
AB  - The American Veterinary Medical Association (AVMA) Council on Education (COE) has
      challenged veterinary schools to improve self-assessment of curricular outcomes.
      One way to assess the quality of education is to gather feedback from alumni. To
      successfully gather feedback using a questionnaire, questions must be pertinent
      to veterinary education and include quantifiable responses. Several principles
      must be applied in questionnaire development to ensure that the questions address
      the intended issues, that questions are interpreted correctly and consistently,
      and that responses are quantifiable. The objectives of the questionnaire for
      alumni of Mississippi State University's College of Veterinary Medicine (MSU-CVM)
      were twofold: (1) to determine whether graduates were comparable to their US
      peers in terms of work opportunities and salary, and (2) to evaluate how well the
      CVM curriculum prepared students to begin their veterinary careers. Demographic
      categories used by the AVMA and published knowledge, skills, attitudes, and
      aptitudes of veterinary graduates were used in developing the questions. College
      specific questions, such as those relating to student activities and impressions
      of college resources, were also incorporated. Questionnaires were mailed to
      participants, who could respond via the World Wide Web. Questionnaire results
      allowed leaders within the college to determine which aspects of alumni's
      experiences were exceptionally positive, which needed immediate response, and
      which might require further study. This article describes the application of
      principles in developing, administering, and analyzing responses to a
      questionnaire regarding veterinary education.

PMID- 18326783
TI  - Veterinary e-CPD: a new model for providing online continuing professional
      development for the veterinary profession.
AB  - Continuing professional development (CPD) is widely recognized as an important
      element in effective lifelong learning for veterinary surgeons. Traditional
      methods of CPD do not suit all learners, as issues such as location, time, cost,
      and structure sometimes prevent individuals from completing the required number
      of CPD study hours per year. The rapid development of the Internet, and with it
      the increasing scope and sophistication of e-learning, provides new opportunities
      to address some of these constraints on the provision of CPD. This article
      describes one way in which e-learning has been deployed effectively to support
      veterinary surgeons in practice. Since 2003, a series of six-week e-CPD courses
      has been offered by the Royal Veterinary College (RVC) in an online format, with
      no face-to-face teaching component. Participants enrolled in courses from May
      2006 to January 2007 were found to come from 23 different countries. Analysis of
      feedback forms indicates a general satisfaction with this new way of studying,
      with a significant majority of participants stating that they would wish to use
      this approach again in future. The feedback indicates that e-learning can offer
      an effective alternative to traditional face-to-face courses and that its
      popularity is likely to grow in future as veterinarians become increasing
      familiar with and confident about working online.

PMID- 18326784
TI  - Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib
      for the treatment of dermal fibrosis.
AB  - Abelson kinase (c-abl) and platelet-derived growth factor (PDGF) are key players
      in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was
      to evaluate the antifibrotic potential of dasatinib and nilotinib, 2 novel
      inhibitors of c-abl and PDGF, which are well tolerated and have recently been
      approved. Dasatinib and nilotinib dose-dependently reduced the mRNA and protein
      levels of extracellular matrix proteins in human stimulated dermal fibroblasts
      from SSc patients (IC(50) of 0.5-2.0 nM for dasatinib and 0.8-2.5 nM for
      nilotinib). In a mouse model of bleomycin-induced dermal fibrosis, dasatinib and
      nilotinib potently reduced the dermal thickness, the number of myofibroblasts,
      and the collagen content of the skin in a dose-dependent manner at well-tolerated
      doses. These data indicate that dasatinib and nilotinib potently inhibit the
      synthesis of extracellular matrix in vitro and in vivo at biologically relevant
      concentrations. Thus, we provide the first evidence that dasatinib and nilotinib
      might be promising drugs for the treatment of patients with SSc.

PMID- 18326786
TI  - Gut microbiota modulation with norfloxacin and ampicillin enhances glucose
      tolerance in mice.
AB  - Recent data suggest that the gut microbiota plays a significant role in fat
      accumulation. However, it is not clear whether gut microbiota is involved in the
      pathophysiology of type 2 diabetes. To assess this issue, we modulated gut
      microbiota via antibiotics administration in two different mouse models with
      insulin resistance. Results from dose-determination studies showed that a
      combination of norfloxacin and ampicillin, at a dose of 1 g/L, maximally
      suppressed the numbers of cecal aerobic and anaerobic bacteria in ob/ob mice.
      After a 2-wk intervention with the antibiotic combination, both ob/ob and diet
      induced obese and insulin-resistant mice showed a significant improvement in
      fasting glycemia and oral glucose tolerance. The improved glycemic control was
      independent of food intake or adiposity because pair-fed ob/ob mice were as
      glucose intolerant as the control ob/ob mice. Reduced liver triglycerides and
      increased liver glycogen correlated with improved glucose tolerance in the
      treated mice. Concomitant reduction of plasma lipopolysaccharides and increase of
      adiponectin further supported the antidiabetic effects of the antibiotic
      treatment in ob/ob mice. In summary, modulation of gut microbiota ameliorated
      glucose tolerance of mice by altering the expression of hepatic and intestinal
      genes involved in inflammation and metabolism, and by changing the hormonal,
      inflammatory, and metabolic status of the host.

PMID- 18326785
TI  - Rapid repair of UVA-induced oxidized purines and persistence of UVB-induced
      dipyrimidine lesions determine the mutagenicity of sunlight in mouse cells.
AB  - Despite the predominance of ultraviolet A (UVA) relative to UVB in terrestrial
      sunlight, solar mutagenesis in humans and rodents is characterized by mutations
      specific for UVB. We have investigated the kinetics of repair of UVA- and UVB
      induced DNA lesions in relation to mutagenicity in transgenic mouse fibroblasts
      irradiated with equilethal doses of UVA and UVB in comparison to simulated
      sunlight UV (SSL). We have also analyzed mutagenesis-derived carcinogenesis in
      sunlight-associated human skin cancers by compiling the published data on
      mutation types found in crucial genes in nonmelanoma and melanoma skin cancers.
      Here, we demonstrate a resistance to repair of UVB-induced cis-syn cyclobutane
      pyrimidine-dimers (CPDs) together with rapid removal of UVA-induced oxidized
      purines in the genome overall and in the cII transgene of SSL-irradiated cells.
      The spectra of mutation induced by both UVB and SSL irradiation in this
      experimental system are characterized by significant increases in relative
      frequency of C-->T transitions at dipyrimidines, which are the established
      signature mutation of CPDs. This type of mutation is also the predominant
      mutation found in human nonmelanoma and melanoma tumor samples in the TP53,
      CDKN2, PTCH, and protein kinase genes. The prevailing role of UVB over UVA in
      solar mutagenesis in our test system can be ascribed to different kinetics of
      repair for lesions induced by the respective UV irradiation.

PMID- 18326787
TI  - Construction of a functional CMP-sialic acid biosynthesis pathway in Arabidopsis.
AB  - Previous studies have reported that plants contain negligible amounts of free or
      protein-bound N-acetylneuraminic acid (Neu5Ac). This is a major disadvantage for
      the use of plants as a biopharmaceutical expression system, since N-glycans with
      terminal Neu5Ac residues are important for the biological activities and half
      lives of recombinant therapeutic glycoproteins in humans. For the synthesis of
      Neu5Ac-containing N-glycans, plants have to acquire the ability to synthesize
      Neu5Ac and its nucleotide-activated derivative, cytidine monophospho-N
      acetylneuraminic acid. In this study, we have generated transgenic Arabidopsis
      (Arabidopsis thaliana) plants expressing three key enzymes of the mammalian
      Neu5Ac biosynthesis pathway: UDP-N-acetylglucosamine 2-epimerase/N
      acetylmannosamine kinase, N-acetylneuraminic acid phosphate synthase, and CMP-N
      acetylneuraminic acid synthetase. Simultaneous expression of UDP-N
      acetylglucosamine 2-epimerase/N-acetylmannosamine kinase and N-acetylneuraminic
      acid phosphate synthase resulted in the generation of significant Neu5Ac amounts
      (1,275 nmol g(-1) fresh weight in leaves) in planta, which could be further
      converted to cytidine monophospho-N-acetylneuraminic acid (2.4 nmol g(-1) fresh
      weight in leaves) by coexpression of CMP-N-acetylneuraminic acid synthetase.
      These findings are a major step toward the production of Neu5Ac-containing
      glycoproteins in plants.

PMID- 18326788
TI  - A third phytoene synthase is devoted to abiotic stress-induced abscisic acid
      formation in rice and defines functional diversification of phytoene synthase
      genes.
AB  - We here report on the characterization of a novel third phytoene synthase gene
      (PSY) in rice (Oryza sativa), OsPSY3, and on the differences among all three PSY
      genes with respect to the tissue-specific expression and regulation upon various
      environmental stimuli. The two already known PSYs are under phytochrome control
      and involved in carotenoid biosynthesis in photosynthetically active tissues and
      exhibit different expression patterns during chloroplast development. In
      contrast, OsPSY3 transcript levels are not affected by light and show almost no
      tissue-specific differences. Rather, OsPSY3 transcripts are up-regulated during
      increased abscisic acid (ABA) formation upon salt treatment and drought,
      especially in roots. The simultaneous induction of genes encoding 9-cis
      epoxycarotenoid dioxygenases (NCEDs), involved in the initial steps of ABA
      biosynthesis, indicate that decreased xanthophyll levels are compensated by the
      induction of the third PSY gene. Furthermore, OsPSY3 and the OsNCEDs investigated
      were also induced by the application of ABA, indicating positive feedback
      regulation. The regulatory differences are mirrored by cis-acting elements in the
      corresponding promoter regions, with light-responsive elements for OsPSY1 and
      OsPSY2 and an ABA-response element as well as a coupling element for OsPSY3. The
      investigation of the gene structures and 5' untranslated regions revealed that
      OsPSY1 represents a descendant of an ancient PSY gene present in the common
      ancestor of monocots and dicots. Since the genomic structures of OsPSY2 and
      OsPSY3 are comparable, we conclude that they originated from the most recent
      common ancestor, OsPSY1.

PMID- 18326789
TI  - Isolation and characterization of mutants of common ice plant deficient in
      crassulacean acid metabolism.
AB  - Crassulacean acid metabolism (CAM) is a specialized mode of photosynthesis that
      improves water use efficiency by shifting part or all of net atmospheric CO2
      uptake to the night. Genetic dissection of regulatory and metabolic attributes of
      CAM has been limited by the difficulty of identifying a reliable phenotype for
      mutant screening. We developed a novel and simple colorimetric assay to measure
      leaf pH to screen fast neutron-mutagenized populations of common ice plant
      (Mesembryanthemum crystallinum), a facultative CAM species, to detect CAM
      deficient mutants with limited nocturnal acidification. The isolated CAM
      deficient mutants showed negligible net dark CO2 uptake compared with wild-type
      plants following the imposition of salinity stress. The mutants and wild-type
      plants accumulated nearly comparable levels of sodium in leaves, but the mutants
      grew more slowly than the wild-type plants. The mutants also had substantially
      reduced seed set and seed weight relative to wild type under salinity stress.
      Carbon-isotope ratios of seed collected from 4-month-old plants indicated that C3
      photosynthesis made a greater contribution to seed production in mutants compared
      to wild type. The CAM-deficient mutants were deficient in leaf starch and lacked
      plastidic phosphoglucomutase, an enzyme critical for gluconeogenesis and starch
      formation, resulting in substrate limitation of nocturnal C4 acid formation. The
      restoration of nocturnal acidification by feeding detached leaves of salt
      stressed mutants with glucose or sucrose supported this defect and served to
      illustrate the flexibility of CAM. The CAM-deficient mutants described here
      constitute important models for exploring regulatory features and metabolic
      consequences of CAM.

PMID- 18326790
TI  - The central role of a SNRK2 kinase in sulfur deprivation responses.
AB  - In the absence of sulfur (S), Chlamydomonas reinhardtii increases the abundance
      of several transcripts encoding proteins associated with S acquisition and
      assimilation, conserves S amino acids, and acclimates to suboptimal growth
      conditions. A positive regulator, SAC1 (for sulfur acclimation protein 1), and a
      negative regulator, SAC3, were shown to participate in the control of these
      processes. In this study, we investigated two allelic mutants (ars11 and ars44)
      affected in a gene encoding a SNRK2 (for SNF1-related protein kinase 2) kinase
      designated SNRK2.1. Like the sac1 mutant, both snrk2.1 mutants were deficient in
      the expression of S-responsive genes. Furthermore, the mutant cells bleached more
      rapidly than wild-type cells during S deprivation, although the phenotypes of
      ars11 and ars44 were not identical: ars11 exhibited a more severe phenotype than
      either ars44 or sac1. The phenotypic differences between the ars11 and ars44
      mutants reflected distinct alterations of SNRK2.1 mRNA splicing caused by
      insertion of the marker gene. The ars11 phenotype could be rescued by
      complementation with SNRK2.1 cDNA. In contrast to the nonepistatic relationship
      between SAC3 and SAC1, characterization of the sac3 ars11 double mutant showed
      that SNRK2.1 is epistatic to SAC3. These data reveal the crucial regulatory role
      of SNRK2.1 in the signaling cascade critical for eliciting S deprivation
      responses in Chlamydomonas. The phylogenetic relationships and structures of the
      eight members of the SNRK2 family in Chlamydomonas are discussed.

PMID- 18326791
TI  - Independence and interaction of regions of the INNER NO OUTER protein in growth
      control during ovule development.
AB  - The outer integument of the Arabidopsis (Arabidopsis thaliana) ovule develops
      asymmetrically, with growth and cell division occurring primarily along the
      region of the ovule facing the base of the gynoecium (gynobasal). This process is
      altered in the mutants inner no outer (ino) and superman (sup), which lead to
      absent or symmetrical growth of the outer integument, respectively. INO encodes a
      member of the YABBY family of putative transcription factors, and its expression
      is restricted to the gynobasal side of developing ovules via negative regulation
      by the transcription factor SUP. Other YABBY proteins (e.g. CRABS CLAW [CRC] and
      YABBY3 [YAB3]) can substitute for INO in promotion of integument growth, but do
      not respond to SUP regulation. In contrast, YAB5 fails to promote integument
      growth. To separately investigate the growth-promotive effects of INO and its
      inhibition by SUP, domain swaps between INO and YAB3, YAB5, or CRC were
      assembled. The ability of chimeric YABBY proteins to respond to SUP restriction
      showed a quantitative response proportional to the amount of INO protein and was
      more dependent on C-terminal regions of INO. A different response was seen when
      examining growth promotion where the number and identity of regions of INO in
      chimeric YABBY proteins were not the primary influence on promotion of outer
      integument growth. Instead, promotion of growth required a coordination of
      features along the entire length of the INO protein, suggesting that
      intramolecular interactions between regions of INO may coordinately facilitate
      the intermolecular interactions necessary to promote formation of the outer
      integument.

PMID- 18326792
TI  - The critical role of the intrinsic VSMC proliferation and death programs in
      injury-induced neointimal hyperplasia.
AB  - Postangioplasty and in-stent restenosis remain ominous problems in percutaneous
      coronary intervention where good animal models of restenosis proneness and
      resistance are needed. We accidentally discovered that the carotid arteries (CAs)
      of the Harlan and Sasco substrains of Sprague-Dawley rats display drastically
      different restenosis phenotypes following balloon-induced endothelial denudation.
      When subjected to balloon injury, Sasco CAs exhibited significantly larger
      neointimal mass than did Harlan CAs at both days 14 and 32, as evidenced by a
      higher intima-to-media ratio and a greater number of intimal cells in Sasco CAs.
      This was due to a greater cell proliferation and to a less vigorous apoptosis of
      Sasco neointima, as assessed by 5-bromo-2'-deoxyuridine and terminal
      deoxynucleotidyl transferase-deoxyuridine nick-end labeling staining,
      respectively. At a cellular level, whereas vascular smooth muscle cells (VSMCs)
      isolated from Sasco and Harlan CAs were identical in morphology and in propensity
      to migrate, Sasco VSMCs proliferated more robustly and died far less, suggesting
      that under the exact same microenvironment, Sasco and Harlan VSMCs respond to
      growth and noxious stimuli in a drastically different fashion and that Sasco's
      significantly more robust neointimal proliferation after vascular injury in vivo
      can be accounted for by these intrinsic differences in VSMCs of these substrains
      in vitro. Sasco and Harlan Sprague-Dawley rats as well as VSMCs from these rats
      will prove to be powerful tools to study genes involved in the pathogenesis of
      restenosis.

PMID- 18326793
TI  - Pericardial delivery of omega-3 fatty acid: a novel approach to reducing
      myocardial infarct sizes and arrhythmias.
AB  - Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty
      acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study
      investigated if pericardial delivery of n-3 PUFAs would protect the myocardium
      from ischemic damages and arrhythmias. Acute myocardial infarctions were induced
      in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left
      anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic
      acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused
      within the pericardial space only during the 40-min stabilizing phase, 45 min
      ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were
      very similar between the DHA-treated and control groups. However, DHA therapy
      significantly reduced infarct sizes from 56.8 +/- 4.9% for controls (n = 12) to
      28.8 +/- 7.9% (P < 0.01) for DHA-treated animals (n = 11). Compared with
      controls, DHA-treated animals significantly decreased heart rates and reduced
      ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control
      animals experienced eight episodes of ventricular fibrillation (VF), and two died
      subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA
      treated pigs elicited one episode of VF that was successfully converted via
      defibrillation to normal rhythm; thus, mortality was reduced from 17% in the
      controls to 0% in the DHA-treated animals. These data demonstrate that
      pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant
      arrhythmias and infarct sizes in a porcine infarct model. Pericardial
      administration of n-3 PUFAs could represent a novel approach to treating or
      preventing myocardial infarctions.

PMID- 18326794
TI  - Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function
      in humans.
AB  - Whether the activation of metabolically sensitive skeletal muscle afferents
      (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains
      incompletely understood. A potential explanation for contrasting findings of
      previous reports may be related to differences in the magnitude of muscle
      metaboreflex activation utilized. Therefore, the present study was designed to
      investigate the influence of graded intensities of muscle metaboreflex activation
      on cardiac baroreflex function. In eight healthy subjects (24 +/- 1 yr), the
      graded isolation of the muscle metaboreflex was achieved by post-exercise
      ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric
      handgrip performed at 35% and 45% maximum voluntary contraction, respectively.
      Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid
      pulse trains of neck pressure and neck suction (+40 to -80 Torr) were applied to
      derive carotid baroreflex stimulus-response curves. Mean blood pressure increased
      significantly from rest during PEI-M (+13 +/- 3 mmHg) and was further augmented
      during PEI-H (+26 +/- 4 mmHg), indicating graded metaboreflex activation.
      However, the operating point gain and maximal gain (-0.51 +/- 0.09, -0.48 +/-
      0.13, and -0.49 +/- 0.12 beats.min(-1).mmHg(-1) for rest; PEI-M and PEI-H) of the
      carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M
      and PEI-H (P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex
      function curve was progressively reset rightward from rest to PEI-M to PEI-H,
      with no upward resetting. These findings suggest that the muscle metaboreflex
      contributes to the resetting of the carotid baroreflex control of HR; however, it
      would appear not to influence carotid-cardiac baroreflex responsiveness in
      humans, even with high-intensity activation during PEI.

PMID- 18326795
TI  - Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced
      by intermittent hypoxic stress.
AB  - Intermittent hypoxia due to sleep apnea syndrome is associated with
      cardiovascular diseases. However, the precise mechanisms by which intermittent
      hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim
      of this study was to investigate the role of gp91(phox)-containing NADPH oxidase
      in the development of left ventricular (LV) remodeling induced by intermittent
      hypoxic stress in mice. Male gp91(phox)-deficient (gp91(-/-)) mice (n = 26) and
      wild-type (n = 39) mice at 7-12 wk of age were exposed to intermittent hypoxia
      (30 s of 4.5-5.5% O(2) followed by 30 s of 21% O(2) for 8 h/day during daytime)
      or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic
      function were not changed by intermittent hypoxia in wild-type or gp91(-/-) mice,
      although right ventricular systolic pressure tended to be increased. In wild-type
      mice, intermittent hypoxic stress significantly increased the diameter of
      cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore,
      intermittent hypoxic stress increased superoxide production, 4-hydroxy-2-nonenal
      protein, TNF-alpha and transforming growth factor-beta mRNA, and NF-kappaB
      binding activity in wild-type, but not gp91(-/-), mice. These results suggest
      that gp91(phox)-containing NADPH oxidase plays a crucial role in the
      pathophysiology of intermittent hypoxia-induced LV remodeling through an increase
      of oxidative stress.

PMID- 18326796
TI  - Effects of ischemia and reperfusion on isolated ventricular myocytes from young
      adult and aged Fischer 344 rat hearts.
AB  - This study examined the impact of age on contractile function, Ca(2+)
      homeostasis, and cell viability in isolated myocytes exposed to simulated
      ischemia and reperfusion. Ventricular myocytes were isolated from anesthetized
      young adult (3 mo) and aged (24 mo) male Fischer 344 rats. Cells were field
      stimulated at 4 Hz (37 degrees C), exposed to simulated ischemia, and reperfused
      with Tyrode solution. Cell shortening and intracellular Ca(2+) were measured
      simultaneously with an edge detector and fura-2. Cell viability was assessed by
      Trypan blue exclusion. Ischemia (20-45 min) depressed amplitudes of contraction
      equally in isolated myocytes from young adult and aged animals. The degree of
      postischemic contractile depression (stunning) was comparable in both groups.
      Ca(2+) transient amplitudes were depressed in early reperfusion in young adult
      and aged cells and then recovered to preischemic levels in both groups. Cell
      viability also declined equally in reperfusion in both groups. In short, some
      cellular responses to simulated ischemia and reperfusion were similar in both
      groups. Even so, aged myocytes exhibited a much greater and more prolonged
      accumulation of diastolic Ca(2+) in ischemia and in early reperfusion compared
      with myocytes from younger animals. In addition, the degree of mechanical
      alternans in ischemia increased significantly with age. The observation that
      there is an age-related increase in accumulation of diastolic Ca(2+) in ischemia
      and early reperfusion may account for the increased sensitivity to ischemia and
      reperfusion injury in the aging heart. The occurrence of mechanical alternans in
      ischemia may contribute to contractile dysfunction in ischemia in the aging
      heart.

PMID- 18326797
TI  - The looped heart does not save energy by maintaining the momentum of blood
      flowing in the ventricle.
AB  - Previous studies suggested that the reconstruction or maintenance of
      physiological blood flow paths in the heart is important to obtain a good outcome
      following cardiac surgery, but this concept has no established theoretical
      foundation. We developed a multiscale, multiphysics heart simulator, based on the
      finite element method, and compared the hemodynamics of ventricles with
      physiological and nonphysiological flow paths. We found that the physiological
      flow path did not have an energy-saving effect but facilitated the separation of
      the outflow and inflow paths, so avoiding any mixing of the blood. The work
      performed by the ventricular wall was comparable at slower and faster heart rates
      (physiological vs. nonphysiological, 0.864 vs. 0.874 J, heart rate = 60
      beats/min; and 0.599 vs. 0.590 J, heart rate = 100 beats/min), indicating that
      chiral asymmetry of the flow paths in the mammalian heart has minimal functional
      merit. At lower heart rates, the blood coming in the first beat was cleared
      almost completely by the ninth beat in both models. However, at high heart rates,
      such complete clearance was observed only in the physiological model, whereas
      27.0% of blood remained in the nonphysiological model. This multiscale heart
      simulator provided detailed information on the cardiac mechanics and flow
      dynamics and could be a useful tool in cardiac physiology.

PMID- 18326798
TI  - Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion
      with altered cavernosal vasoreactivity and matrix.
AB  - The number of men with type II diabetes-associated erectile dysfunction (ED)
      continues to grow rapidly; however, the majority of basic science studies has
      examined mechanisms of ED in animal models of type I diabetes. In this study, we
      first establish an in vivo mouse model of type II diabetic ED using the leptin
      receptor mutated db/db and wild-type control BKS mouse. Furthermore, we
      hypothesized that dual mechanistic impairments contribute to the impaired
      erectile function in the type II diabetic mouse, altered vasoreactivity, and
      venoocclusive disorder. In vivo erectile function was measured as intracavernosal
      pressure (ICP) normalized to mean arterial pressure (MAP) following electrical
      stimulation of the cavernosal nerve. Venoocclusion was assessed by the
      maintenance of elevated in vivo ICP following intracorporal saline infusion.
      Vasoreactivity of isolated cavernosum in response to contractile and dilatory
      stimulation was examined in vitro by myography. Collagen and elastin content were
      evaluated by quantification of hydroxyproline and desmosine, respectively, as
      well as by quantitative PCR and histological analysis of isolated cavernosum.
      Erectile function was significantly decreased in db/db vs. BKS mice in a manner
      consistent with impairments in venoocclusive ability and decreased inflow.
      Heightened vasoconstriction and attenuated dilation in cavernosum of db/db vs.
      BKS mice suggest an overall lowered relaxation ability and thus impaired filling
      of the cavernosal spaces. A decrease in desmosine and hydroxyproline as well as
      lowered mRNA levels for tropoelastin, fibrillin-1, and alpha1(I) collagen were
      detected. These vasoreactive and sinusoidal matrix alterations may alter tissue
      compliance dispensability, preventing the normal expansion necessary for
      erection.

PMID- 18326799
TI  - Nitric oxide generation by endothelial cells exposed to shear stress in glass
      tubes perfused with red blood cell suspensions: role of aggregation.
AB  - Endothelial function is modulated by wall shear stress acting on the vessel wall,
      which is determined by fluid velocity and the local viscosity near the vessel
      wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring
      axial migration. The aim of this study was to investigate the role of RBC
      aggregation, with or without altered plasma viscosity, in the mechanically
      induced nitric oxide (NO)-related mechanisms of endothelial cells. Human
      umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of
      cylindrical glass capillaries that were perfused with RBC suspensions having
      normal and increased aggregation at a nominal shear stress of 15 dyn/cm(2). RBC
      aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC
      suspended in normal, autologous plasma, resulting in enhanced aggregation but
      unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma
      containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC
      aggregation but higher plasma viscosity. Compared with normal cells in unmodified
      plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma
      resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of
      endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma
      containing dextran resulted in a NO level that remained elevated, whereas only a
      modest decrease of phosphorylated eNOS level was observed. The results of this
      study suggest that increases of RBC aggregation tendency affect endothelial cell
      functions by altering local blood composition, especially if the alterations of
      RBC aggregation are due to modified cellular properties and not to plasma
      composition changes.

PMID- 18326800
TI  - Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth
      muscle cells of aged rats.
AB  - Mitochondrial biogenesis is involved in the control of cell metabolism, signal
      transduction, and regulation of mitochondrial reactive oxygen species (ROS)
      production. Despite the central role of mitochondria in cellular aging and
      endothelial physiology, there are no studies extant investigating age-related
      alterations in mitochondrial biogenesis in blood vessels. Electronmicroscopy and
      confocal microscopy (en face Mitotracker staining) revealed that in aortas of
      F344 rats, a decline in mitochondrial biogenesis occurs with aging. In aged
      vessels, the expression of the mitochondrial biogenesis factors (including
      mitochondrial transcription factor A and peroxisome proliferator-activated
      receptor-gamma coactivator-1) was decreased. The vascular expression of complex
      I, III, and IV significantly declined with age, whereas aging did not alter the
      expression of complex II and V. Cytochrome c oxidase (COX) expression/activity
      exhibited the greatest age-related decline, which was associated with increased
      mitochondrial ROS production in the aged vessels. In cultured coronary arterial
      endothelial cells, a partial knockdown of COX significantly increased
      mitochondrial ROS production. In conclusion, vascular aging is characterized by a
      decline in mitochondrial mass in the endothelial cells and an altered expression
      of components of the mitochondrial electron transport chain likely due to a
      dysregulation of mitochondrial biogenesis factors. We posit that impaired
      mitochondrial biogenesis and downregulation of COX may contribute to the
      increased mitochondrial oxidative stress in aged endothelial cells.

PMID- 18326801
TI  - Contractile regulation by overexpressed ETA requires intact T tubules in adult
      rat ventricular myocytes.
AB  - Endothelin (ET)-1 regulates the contractility and growth of the heart by binding
      G protein-coupled receptors of the ET type A receptor (ET(A))/ET type B (ET(B))
      receptor family. ET(A), the predominant ET-1 receptor subtype in myocardium, is
      thought to localize preferentially within cardiac T tubules, but the consequences
      of mislocalization are not fully understood. Here we examined the effects of the
      overexpression of ET(A) in conjunction with T-tubule loss in cultured adult rat
      ventricular myocytes. In adult myocytes cultured for 3 to 4 days, the normally
      robust positive inotropic effect (PIE) of ET-1 was lost in parallel with T-tubule
      degeneration and a decline in ET(A) protein levels. In these T tubule-compromised
      myocytes, an overexpression of ET(A) using an adenoviral vector did not rescue
      the responsiveness to ET-1, despite the robust expression in the surface
      sarcolemma. The inclusion of the actin polymerization inhibitor cytochalasin D
      (CD) during culture prevented gross morphological changes including a loss of T
      tubules and a rounding of intercalated discs, but CD alone did not rescue the
      responsiveness to ET-1 or prevent ET(A) downregulation. The rescue of a normal
      PIE in 3- to 4-day cultured myocytes required both an increased expression of
      ET(A) and intact T tubules (preserved with CD). Therefore, the activation of
      ET(A) localized in T tubules was associated with a strong PIE, whereas the
      activation of ET(A) in surface sarcolemma was not. The results provide insight
      into the pathological cardiac conditions in which ET(A) is upregulated and T
      tubule morphology is altered.

PMID- 18326802
TI  - Effects of elastic compression stockings on wall shear stress in deep and
      superficial veins of the calf.
AB  - The purpose of this study was to estimate wall shear stress (WSS) in individual
      vessels of the venous circulation of the calf and quantify the effects of elastic
      compression based on change of vessel geometry and velocity waveform. The great
      saphenous vein and either a peroneal or posterior tibial vein have been imaged in
      four healthy subjects using magnetic resonance imaging, with and without the
      presence of a grade 1 medical stocking. Flow through image-based reconstructed
      geometries was numerically simulated for both a range of steady flow rates and
      ultrasound-derived transient velocity waveforms, scaled to give a standardized
      time averaged flow rate. For steady flow, the stocking produced an average
      percentage increase in mean WSS of approximately 100% in the great saphenous vein
      across a range of 0.125-1.25 ml/s. The percentage increase in the
      peroneal/posterior tibial veins varied from 490 to 650% across a range of 0.5-5
      ml/s. In addition, application of the stocking eliminated periods of very low or
      zero flow from the transient waveforms. The average minimum value of WSS in all
      vessels without the stocking was <0.1 Pa. With the stocking, this was increased
      to 0.7 Pa in the great saphenous and 0.9 Pa in the peroneal/posterior tibial
      veins. The pathophysiological effects of these changes are discussed. In
      conclusion, the flight stocking was effective in raising venous WSS levels in
      prone subjects, and this effect was much more pronounced in the deep vessels. The
      stocking also tended to prevent cessation of flow during periods of increased
      downstream pressure produced by respiration.

PMID- 18326803
TI  - Relationships between regional myocardial wall stress and bioenergetics in hearts
      with left ventricular hypertrophy.
AB  - This study utilized porcine models of postinfarction left ventricular (LV)
      remodeling [myocardial infarction (MI); n = 8] and concentric LV hypertrophy
      secondary to aortic banding (AoB; n = 8) to examine the relationships between
      regional myocardial contractile function (tagged MRI), wall stress (MRI and LV
      pressure), and bioenergetics ((31)P-magnetic resonance spectroscopy).
      Physiological assessments were conducted at a 4-wk time point after MI or AoB
      surgery. Comparisons were made with size-matched normal animals (normal; n = 8).
      Both MI and AoB instigated significant LV hypertrophy. Ejection fraction was not
      significantly altered in the AoB group, but significantly decreased in the MI
      group (P < 0.01 vs. normal and AoB). Systolic and diastolic wall stresses were
      approximately two times greater than normal in the infarct region and border
      zone. Wall stress in the AoB group was not significantly different from that in
      normal hearts. The infarct border zone demonstrated profound bioenergetic
      abnormalities, especially in the subendocardium, where the ratio of PCr/ATP
      decreased from 1.98 +/- 0.16 (normal) to 1.06 +/- 0.30 (MI; P < 0.01). The
      systolic radial thickening fraction and the circumferential shortening fraction
      in the anterior wall were severely reduced (MI, P < 0.01 vs. normal). The radial
      thickening fraction and circumferential shortening fraction in the AoB group were
      not significantly different from normal. The severely elevated wall stress in the
      infarct border zone was associated with a significant increase in chemical energy
      demand and abnormal myocardial energy metabolism. Such severe metabolic
      perturbations cannot support normal cardiac function, which may explain the
      observed regional contractile abnormalities in the infarct border zone.

PMID- 18326804
TI  - Sexual dimorphism in rabbit aortic endothelial function under acute hyperglycemic
      conditions and gender-specific responses to acute 17beta-estradiol.
AB  - Epidemiological data suggest that hyperglycemia abrogates the gender-based
      cardiovascular protection possibly associated with estrogens. This study was
      designed to investigate 1) whether rabbit aortic rings show gender differences in
      the development of abnormal endothelium-dependent vasodilation (EDV) under acute
      hyperglycemic conditions, 2) the potential role of PKC isoforms and superoxide
      (O2-) in acute hyperglycemia-induced vascular dysfunction, and 3) the effect of
      acute estrogen administration on hyperglycemia-induced endothelial dysfunction in
      male and female rabbits. EDV to ACh was determined before and after 3 h of
      treatment with high glucose (HG) in phenylephrine-precontracted aortic rings from
      male and female New Zealand White rabbits. Similar experiments were conducted in
      the presence of inhibitors of PKC-alpha, PKC-beta, and PKC-delta or an O2-
      scavenger. The effect of acute estrogen administration was evaluated in the
      presence and absence of HG. Finally, mRNA expression of PKC isoforms was measured
      by real-time PCR. We found that 1) 3 h of incubation with HG impairs EDV to a
      greater extent in female than male aorta, 2) inhibition of PKC-beta or O2-
      prevents HG-induced impairment of EDV in female aorta, 3) acute 17beta-estradiol
      aggravates HG-induced endothelial dysfunction in female, but not male, aorta, and
      4) PKC-alpha and PKC-beta expression are significantly higher in female than male
      aorta. This study reveals the predisposition of female rabbit aorta to vascular
      injury under hyperglycemic conditions, possibly via activation of PKC-beta and O2
      production. Furthermore, it suggests that, under hyperglycemic conditions, acute
      estrogen treatment is detrimental to endothelial function in female rabbits.

PMID- 18326805
TI  - Progressive nature of chronic mitral regurgitation and the role of tissue Doppler
      derived indexes.
AB  - The aim of this study was to determine whether severe mitral regurgitation (MR)
      is progressive and whether tissue-Doppler (TD)-derived indexes can detect early
      left ventricular (LV) dysfunction in chronic severe MR. Percutaneous rupture of
      mitral valve chordae was performed in pigs (n = 8). Before MR (baseline),
      immediately after MR (post-MR), and at 1 and 3 mo after MR, cardiac function was
      assessed using conventional and TD-derived indexes. The severity of MR was
      quantified using regurgitant fraction and effective regurgitant orifice area
      (EROA). In all animals, MR was severe. On follow-up, the LV dilated progressively
      over time, but LV ejection fraction did not decrease. With the increase in LV
      dimensions, the forward stroke volume remained unchanged, but the mitral annular
      dimensions, EROA, and regurgitant fraction increased (EROA = 41 +/- 2 and 51 +/-
      2 mm(2) post-MR and at 3 mo, respectively, P < 0.01). Peak systolic myocardial
      velocities, strain, and strain rate increased acutely post-MR and remained
      elevated at 1 mo but declined by 3 mo (anterior strain rate = 2.9 +/- 0.1 and 2.4
      +/- 0.2 s(-1) post-MR and at 3 mo, respectively, P < 0.001). Therefore, in a
      chronic model of MR, serial echocardiography demonstrated that MR begets MR and
      that those TD-derived indexes that initially increased post-MR decreased to
      baseline before any changes in LV ejection fraction.

PMID- 18326806
TI  - Cerebral microvascular nNOS responds to lowered oxygen tension through a
      bumetanide-sensitive cotransporter and sodium-calcium exchanger.
AB  - Na(+) cotransporters have a substantial role in neuronal damage during brain
      hypoxia. We proposed these cotransporters have beneficial roles in oxygen-sensing
      mechanisms that increase periarteriolar nitric oxide (NO) concentration ([NO])
      during mild to moderate oxygen deprivation. Our prior studies have shown that
      cerebral neuronal NO synthase (nNOS) is essential for [NO] responses to decreased
      oxygen tension and that endothelial NO synthase (eNOS) is of little consequence.
      In this study, we explored the mechanisms of three specific cotransporters known
      to play a role in the hypoxic state: KB-R7943 for blockade of the Na(+)/Ca(2+)
      exchanger, bumetanide for the Na(+)-K(+)-2Cl(-) cotransporter, and amiloride for
      Na(+)/H(+) cotransporters. In vivo measurements of arteriolar diameter and [NO]
      at normal and locally reduced oxygen tension in the rat parietal cortex provided
      the functional analysis. As previously found for intestinal arterioles,
      bumetanide-sensitive cotransporters are primarily responsible for sensing reduced
      oxygen because the increased [NO] and dilation were suppressed. The Na(+)/Ca(2+)
      exchanger facilitated increased NO formation because blockade also suppressed
      [NO] and dilatory responses to decreased oxygen. Amiloride-sensitive Na(+)/H(+)
      cotransporters did not significantly contribute to the microvascular regulation.
      To confirm that nNOS rather than eNOS was primarily responsible for NO
      generation, eNOS was suppressed with the fusion protein cavtratin for the
      caveolae domain of eNOS. Although the resting [NO] decreased and arterioles
      constricted as eNOS was suppressed, most of the increased NO and dilatory
      response to oxygen were preserved because nNOS was functional. Therefore, nNOS
      activation secondary to Na(+)-K(+)-2Cl(-) cotransporter and Na(+)/Ca(2+)
      exchanger functions are key to cerebral vascular oxygen responses.

PMID- 18326807
TI  - Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal
      vasoconstriction during muscle stretch in humans.
AB  - During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal
      vasoconstriction. Animal studies suggest that prostaglandins generated within the
      contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that
      local prostaglandin blockade would attenuate renal vasoconstriction during
      ischemic muscle stretch. Eleven healthy subjects performed static handgrip before
      and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into
      the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex
      Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG)
      were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by
      PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular
      resistance (RVR, calculated as MAP/RBV) was increased from baseline during all
      paradigms except during PHGMI + stretch after the ketorolac Bier block trial
      where RVR did not change from baseline. Before Bier block, RVR rose more during
      PHGMI + stretch than during PHGMI alone (P < .01). Similar results were found
      after a saline Bier block trial (Delta53 +/- 13% vs. Delta35 +/- 10%; P < 0.01).
      However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch
      than during PHGMI alone [Delta39 +/- 8% vs. Delta40 +/- 12%; P = not significant
      (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch (P =
      NS). Passive muscle stretch during ischemia augments renal vasoconstriction,
      suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition
      of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated
      constrictor responses. Thus mechanoreceptor sensitization in humans is linked to
      the production of prostaglandins.

PMID- 18326808
TI  - Deficient renal 20-HETE release in the diabetic rat is not the result of
      oxidative stress.
AB  - We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the
      isolated perfused kidney of diabetic rats is greatly reduced compared with age
      matched control rats. The present studies were undertaken to examine potential
      mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced
      diabetes of 3-4 wk duration. A role for oxidative stress was excluded, inasmuch
      as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not
      affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric
      oxide formation with nitro-l-arginine methyl ester or aldose reductase with
      zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney.
      Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the
      expression/activity of which is increased in diabetes, we included indomethacin
      in the perfusate of the isolated kidney to inhibit COX but found no effect on 20
      HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase
      expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that
      would restore release of 20-HETE from the diabetic rat kidney. However,
      fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but
      increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk
      to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl
      reversed the renal deficit in 20-HETE. We conclude that oxidative stress,
      increased aldose reductase activity, or increased COX activity does not
      contribute to the renal deficit of 20-HETE in diabetes, which may be directly
      related to insulin deficiency.

PMID- 18326809
TI  - First-order approximation for the pressure-flow relationship of spontaneously
      contracting lymphangions.
AB  - To return lymph to the great veins of the neck, it must be actively pumped
      against a pressure gradient. Mean lymph flow in a portion of a lymphatic network
      has been characterized by an empirical relationship (P(in) - P(out) = -P(p) +
      R(L)Q(L)), where P(in) - P(out) is the axial pressure gradient and Q(L) is mean
      lymph flow. R(L) and P(p) are empirical parameters characterizing the effective
      lymphatic resistance and pump pressure, respectively. The relation of these
      global empirical parameters to the properties of lymphangions, the segments of a
      lymphatic vessel bounded by valves, has been problematic. Lymphangions have a
      structure like blood vessels but cyclically contract like cardiac ventricles;
      they are characterized by a contraction frequency (f) and the slopes of the end
      diastolic pressure-volume relationship [minimum value of resulting elastance
      (E(min))] and end-systolic pressure-volume relationship [maximum value of
      resulting elastance (E(max))]. Poiseuille's law provides a first-order
      approximation relating the pressure-flow relationship to the fundamental
      properties of a blood vessel. No analogous formula exists for a pumping
      lymphangion. We therefore derived an algebraic formula predicting lymphangion
      flow from fundamental physical principles and known lymphangion properties.
      Quantitative analysis revealed that lymph inertia and resistance to lymph flow
      are negligible and that lymphangions act like a series of interconnected
      ventricles. For a single lymphangion, P(p) = P(in) (E(max) - E(min))/E(min) and
      R(L) = E(max)/f. The formula was tested against a validated, realistic
      mathematical model of a lymphangion and found to be accurate. Predicted flows
      were within the range of flows measured in vitro. The present work therefore
      provides a general solution that makes it possible to relate fundamental
      lymphangion properties to lymphatic system function.

PMID- 18326810
TI  - Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2,
      MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts.
AB  - Venous injury and subsequent venous stenosis formation are responsible for
      hemodialysis graft failure. Our hypothesis is that these pathological changes are
      in part related to changes in wall shear stress (WSS) that results in the
      activation of matrix regulatory proteins causing subsequent venous stenosis
      formation. In the present study, we examined the serial changes in WSS, blood
      flow, and luminal vessel area that occur subsequent to the placement of a
      hemodialysis graft in a porcine model of chronic renal insufficiency. We then
      determined the corresponding histological, morphometric, and kinetic changes of
      several matrix regulatory proteins including VEGF-A, its receptors, matrix
      metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase
      (TIMP)-1, and TIMP-2. WSS was estimated by obtaining blood flow and luminal
      vessel area by performing phase-contrast MRI with magnetic resonance angiography
      in 21 animals at 1 day after graft placement and prior to death on day 3 (n = 7),
      day 7 (n = 7), and day 14 (n = 7). At all time points, the mean WSS at the vein
      to-graft anastomosis was significantly higher than that at the control vein (P <
      0.05). WSS had a bimodal distribution with peaks on days 1 and 7 followed by a
      significant reduction in WSS by day 14 (P < 0.05 compared with day 7) and a
      decrease in luminal vessel area compared with control vessels. By day 3, there
      was a significant increase in VEGF-A and pro-MMP-9 followed by, on day 7,
      increased pro-MMP-2, active MMP-2, and VEGF receptor (VEGFR)-2 (P < 0.05) and, by
      day 14, increased VEGFR-1 and TIMP-1 (P < 0.05) at the vein-to-graft anastomosis
      compared with control vessels. Over time, the neointima thickened and was
      composed primarily of alpha-smooth muscle actin-positive cells with increased
      cellular proliferation. Our data suggest that hemodialysis graft placement leads
      to early increases in WSS, VEGF-A, and pro-MMP-9 followed by subsequent increases
      in pro-MMP-2, active MMP-2, VEGFR-1, VEGFR-2, and TIMP-1, which may contribute to
      the development of venous stenosis.

PMID- 18326811
TI  - In vivo quantitative autoradiographic analysis of brain muscarinic receptor
      occupancy by antimuscarinic agents for overactive bladder treatment.
AB  - We evaluated the effects of five clinically used antimuscarinic agents for
      overactive bladder (OAB) treatment on in vivo muscarinic receptor binding in rat
      brain by quantitative autoradiography. There was a dose-related decrease in in
      vivo specific +N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB) binding in
      each brain region of rats 10 min after i.v. injection of oxybutynin, propiverine,
      solifenacin, and tolterodine. Rank order of the i.v. dose for 50% receptor
      occupancy (RO(50)) of antimuscarinic agents in rat brain regions was propiverine
      > solifenacin > tolterodine, oxybutynin. There was a good linear relationship
      between in vivo (pRO(50) values in the rat hippocampus) and in vitro (pK(i)
      values in human M(1) receptors) receptor binding activities of propiverine,
      solifenacin, and tolterodine. The observed RO(50) value of oxybutynin was
      approximately five times smaller than the predicted in vitro K(i) value. The dose
      ratios of antimuscarinic agents for the brain receptor occupancy (RO(50)) to the
      inhibition of carbachol- and volume-induced increases in intravesical pressure
      (ID(50)), which reflects in vivo selectivity for the urinary bladder over the
      brain, were greater for solifenacin, tolterodine, and propiverine than
      oxybutynin. Darifenacin displayed only a slight decrease in specific [11C](+)3
      MPB binding in the rat brain regions, and it was not dose-related. In conclusion,
      in vivo quantitative autoradiographic analysis of brain muscarinic receptor
      occupancy may provide fundamental basis for managing central nervous system (CNS)
      side effects in antimuscarinic therapy for OAB. It is suggested that in the
      treatment of OAB, CNS side effects can be avoided by antimuscarinic agents with
      high selectivity for the urinary bladder over the brain.

PMID- 18326812
TI  - The T- and L-type calcium channel blocker (CCB) mibefradil attenuates leg edema
      induced by the L-type CCB nifedipine in the spontaneously hypertensive rat: a
      novel differentiating assay.
AB  - Among the L-type calcium channel blockers (CCBs), particularly dihydropyridines
      like nifedipine [1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5
      pyridinedicarboxylic acid dimethyl ester], a common adverse effect is
      vasodilatory edema. Newer CCBs, such as the T- and L-type CCB, mibefradil
      [(1S,2S)-2-[2[[3-(2-benzimidazolylpropyl]methylamino]ethyl]-6-fluoro-1,2,3,4
      tetrahydro-1-isopropyl-2-naphthyl methoxyacetate dihydrochloride hydrate],
      demonstrate antihypertensive efficacy similar to that of their predecessors but
      seem to have a reduced propensity to cause edema. Using a magnetic resonance
      imaging (MRI) T(2) mapping technique, we investigated the ability of mibefradil
      to reduce extracellular water accumulation caused by the L-type CCB, nifedipine,
      in the hindleg skeletal muscle of the spontaneously hypertensive rat. Mibefradil
      (10 mg/kg i.v.) and nifedipine (1 mg/kg i.v.) lowered mean arterial blood
      pressure by 97 +/- 5 and 77 +/- 4 mm Hg, respectively. MRI edema index (expressed
      as percentage increase of integral T(2) over predrug control) was significantly
      higher with nifedipine (2606 +/- 86%; p < 0.05) than with mibefradil (981 +/-
      171%) measured 30 to 60 min after the start of drug infusion. The hindleg edema
      caused by nifedipine was dose dependently decreased by coadministration of
      mibefradil (0, 0.3, or 3 mg/kg). The hindleg edema formation was not due to
      albumin leakage into the interstitial space based on immunostaining. However, a
      4.2-fold increase in the arterial L-/T-type CC mRNA expression ratio was observed
      compared with the venous L/T ratio as shown by quantitative reverse transcription
      polymerase chain reaction. These results demonstrate the novel utility of MRI to
      measure extravascular water after acute exposure to CCBs and indicate that T-type
      CCB activity may reduce L-type CCB-induced vasodilatory edema in the skeletal
      muscle vasculature, possibly by a differential effect on arteriole and venule
      dilatation.

PMID- 18326813
TI  - Simultaneously targeting CD45 significantly increases cytotoxicity of the anti
      CD33 immunoconjugate, gemtuzumab ozogamicin, against acute myeloid leukemia (AML)
      cells and improves survival of mice bearing human AML xenografts.
AB  - Targeting CD33 or CD45 is currently exploited for immunotherapy of acute myeloid
      leukemia (AML). Gemtuzumab ozogamicin (GO), an immunoconjugate of an anti-CD33
      antibody that facilitates cellular uptake of a toxic calicheamicin-gamma(1)
      derivative, induces complete remissions in a subset of patients with AML. We
      herein tested whether simultaneous targeting of CD45 could improve GO
      cytotoxicity against AML cell lines and primary AML cells. We found that the anti
      CD45 antibody, BC8, dose-dependently increased cytotoxicity induced by GO, and,
      to a lesser degree, free calicheamicin-gamma(1). BC8 promoted CD33 endocytosis,
      suggesting that its effect on GO cytotoxicity may be, at least partly, due to
      increased uptake and intracellular GO availability. Finally, compared with either
      agent alone, BC8 combined with GO resulted in marked tumor growth inhibition and
      superior survival rates of mice bearing human AML xenografts. These data suggest
      that further study of this antibody combination for clinical use in AML is
      warranted.

PMID- 18326814
TI  - Calcitonin receptor-like receptor guides arterial differentiation in zebrafish.
AB  - The calcitonin receptor-like receptor (crlr) is a major endothelial cell receptor
      for adrenomedullin, a peptide vasodilator involved in cardiovascular development,
      homeostasis, and disease. Here, we used the zebrafish (Danio rerio) model to
      characterize the role of crlr in vascular development. Crlr is expressed within
      somites from the 4- to the 13-somite stage and by arterial progenitors and axial
      vessels during zebrafish development. Loss of crlr results in profound
      alterations in vascular development and angiogenesis, including atrophic trunk
      dorsal aorta and interruption of anterior aortic bifurcation, delay in
      intersomitic vessel development, and lack of blood circulation. Remarkably, crlr
      morphants are characterized by the loss of arterial endothelial cell identity in
      dorsal aorta, as shown by the lack of expression of the arterial markers ephrin
      B2a, DeltaC, and notch5. Down-regulation of crlr affects vascular endothelial
      growth factor (vegf) expression, whereas vegf overexpression is sufficient to
      rescue arterial differentiation in crlr morphants. Finally, genetic and
      biochemical evidences indicate that somitic crlr expression is under the control
      of sonic hedgehog. These data demonstrate that crlr plays a nonredundant role in
      arterial differentiation, representing a novel element of the sonic hedgehog-vegf
      notch signaling cascade that controls arterial/venous fate.

PMID- 18326815
TI  - Use of IGHV3-21 in chronic lymphocytic leukemia is associated with high-risk
      disease and reflects antigen-driven, post-germinal center leukemogenic selection.
AB  - We examined the chronic lymphocytic leukemia (CLL) cells of 2457 patients
      evaluated by the CLL Research Consortium (CRC) and found that 63 (2.6%) expressed
      immunoglobulin (Ig) encoded by the Ig heavy-chain-variable-region gene (IGHV),
      IGHV3-21. We identified the amino acid sequence DANGMDV (motif-1) or
      DPSFYSSSWTLFDY (motif-2) in the Ig heavy-chain (IgH) third complementarity
      determining region (HCDR3) of IgH, respectively, used by 25 or 3 cases. The IgH
      with HCDR3 motif-1 or motif-2, respectively, was paired with Ig light chains
      (IgL) encoded by IGLV3-21 or IGKV3-20, suggesting that these Ig had been selected
      for binding to conventional antigen(s). Cases that had HCDR3 motif-1 had a median
      time from diagnosis to initial therapy comparable with that of cases without a
      defined HCDR3 motif, as did cases that used mutated IGHV3-21 (n = 27) versus
      unmutated IGHV3-21 (n = 30). Of 7 examined cases that used Ig encoded by IGHV3
      21/IGLV3-21, we found that 5 had a functionally rearranged IGKV allele that
      apparently had incurred antigendriven somatic mutations and subsequent
      rearrangement with KDE. This study reveals that CLL cells expressing IGHV3
      21/IGLV3-21 most likely were derived from B cells that had experienced somatic
      mutation and germinal-center maturation in an apparent antigen-driven immune
      response before undergoing Ig-receptor editing and after germinal-center
      leukemogenic selection.

PMID- 18326816
TI  - Dysregulation of TGF-beta signaling and regulatory and effector T-cell function
      in virus-induced neuroinflammatory disease.
AB  - We previously demonstrated that CD4(+)CD25(+) T regulatory cells (Tregs),
      important for the maintenance of immune tolerance and prevention of autoimmune
      disease, from patients with human T lymphotropic virus type I (HTLV-I)-associated
      myelopathy/tropical spastic paraparesis (HAM/TSP) exhibit reduced Foxp3
      expression and Treg suppressor function compared with healthy donors. Since TGF
      beta signaling has been previously reported to be critical for both Foxp3
      expression and Treg function, we examined whether this signaling pathway was
      dysregulated in patients with HAM/TSP. Levels of TGF-beta receptor II (TGF
      betaRII) as well as Smad7 (a TGF-beta-inducible gene) were significantly reduced
      in CD4(+) T cells in patients with HAM/TSP compared with healthy donors, and the
      expression of TGF-betaRII inversely correlated with the HTLV-I tax proviral load.
      Importantly, both CD4(+)CD25(+) and CD4(+)CD25(-) T cells from HAM/TSP patients
      exhibited reduced TGF-betaRII expression compared with healthy donors, which was
      associated with functional deficits in vitro, including a block in TGF-beta
      inducible Foxp3 expression that inversely correlated with the HTLV-I tax proviral
      load, loss of Treg suppressor function, and escape of effector T cells from Treg
      mediated control. This evidence suggests that a virus-induced breakdown of immune
      tolerance affecting both regulatory and effector T cells contributes to the
      pathogenesis of HAM/TSP.

PMID- 18326817
TI  - Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands
      and receptors independently of neogenin.
AB  - Hemojuvelin (HJV) is a coreceptor for bone morphogenetic protein (BMP) signaling
      that regulates hepcidin expression and iron metabolism. However, the precise
      combinations of BMP ligands and receptors used by HJV remain unknown. HJV has
      also been demonstrated to bind to neogenin, but it is not known whether this
      interaction has a role in regulating hepcidin expression. In the present study,
      we show that BMP-2, BMP-4, and BMP-6 are endogenous ligands for HJV in hepatoma
      derived cell lines, and that all 3 of these ligands are expressed in human liver.
      We demonstrate in vitro that HJV selectively uses the BMP type II receptors
      ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by
      BMP-2 and BMP-4. Interestingly, ActRIIA is the predominant BMP type II receptor
      expressed in human liver. While HJV can use all 3 BMP type I receptors (ALK2,
      ALK3, and ALK6) in vitro, only ALK2 and ALK3 are detected in human liver.
      Finally, we show that HJV-induced BMP signaling and hepcidin expression are not
      altered by neogenin overexpression or by inhibition of endogenous neogenin
      expression. Thus, HJV-mediated BMP signaling and hepcidin regulation occur via a
      distinct subset of BMP ligands and BMP receptors, independently of neogenin.

PMID- 18326818
TI  - Development and dynamics of robust T-cell responses to CML under imatinib
      treatment.
AB  - Novel molecular targeted therapies, such as imatinib for chronic myelogenous
      leukemia (CML), represent the first agents that inhibit cancer cells more than
      other dividing cells, such as immune cells. We hypothesize that imatinib may
      create a window in which the immune response is partially restored while
      apoptotic leukemic cells are present, thus rendering leukemic cells immunogenic
      as patients enter remission. To detect and quantify antileukemia immune responses
      in an antigen-unbiased way, we used cryopreserved autologous pretreatment blood
      samples (representing predominantly leukemic cells) as stimulators to detect
      antileukemia T-cell responses in CML patients in remission on imatinib. We
      studied patients over time to address the dynamics of such responses. Our data
      show that antileukemia T-cell responses develop in the majority of CML patients
      (9 of 14) in remission and that CD4(+) T cells producing tumor necrosis factor
      alpha (median 17.6%) represent the major response over interferon-gamma. This
      confirms the immune system's ability to respond to leukemia under certain
      conditions. Such responses may be further amplified as a potential therapy that
      synergizes with imatinib for improved control of CML.

PMID- 18326819
TI  - The MADS transcription factor Mef2c is a pivotal modulator of myeloid cell fate.
AB  - Mef2c is a MADS (MCM1-agamous-deficient serum response factor) transcription
      factor best known for its role in muscle and cardiovascular development. A causal
      role of up-regulated MEF2C expression in myelomonocytic acute myeloid leukemia
      (AML) has recently been demonstrated. Due to the pronounced monocytic component
      observed in Mef2c-induced AML, this study was designed to assess the importance
      of Mef2c in normal myeloid differentiation. Analysis of bone marrow (BM) cells
      manipulated to constitutively express Mef2c demonstrated increased monopoiesis at
      the expense of granulopoiesis, whereas BM isolated from Mef2c(Delta/-) mice
      showed reduced levels of monocytic differentiation in response to cytokines.
      Mechanistic studies showed that loss of Mef2c expression correlated with reduced
      levels of transcripts encoding c-Jun, but not PU.1, C/EBPalpha, or JunB
      transcription factors. Inhibiting Jun expression by short-interfering RNA
      impaired Mef2c-mediated inhibition of granulocyte development. Moreover,
      retroviral expression of c-Jun in BM cells promoted monocytic differentiation.
      The ability of Mef2c to modulate cell-fate decisions between monocyte and
      granulocyte differentiation, coupled with its functional sensitivity to
      extracellular stimuli, demonstrate an important role in immunity--and, consistent
      with findings of other myeloid transcription factors, a target of oncogenic
      lesions in AML.

PMID- 18326820
TI  - Alpha4beta1 integrin and 190-kDa CD44v constitute a cell surface docking complex
      for gelatinase B/MMP-9 in chronic leukemic but not in normal B cells.
AB  - As B-cell chronic lymphocytic leukemia (B-CLL) progresses, malignant cells
      extravasate and infiltrate lymphoid tissues. Several molecules, including
      gelatinase B/MMP-9, contribute to these processes. Although mainly a secreted
      protease, some MMP-9 is present at the B-CLL cell surface and the function, mode
      of anchoring, and interactions of this MMP-9 are unknown. Here we show that anti
      MMP-9 antibodies immunoprecipitated a 190-kDa CD44v isoform and alpha4beta1
      integrin from B-CLL cells, but not from normal B cells. Function-blocking
      antibodies to alpha4beta1 or CD44, or transfection with specific siRNAs,
      decreased cell-associated proMMP-9 and increased the secreted form. B-CLL cells
      attached to and bound proMMP-9 and active MMP-9, and this was inhibited by
      blocking the expression or function of alpha4beta1 or CD44. The MMP-9 hemopexin
      domain was critical in these interactions. alpha4beta1 and 190-kDa CD44v (but not
      CD44H) formed a complex at the cell surface, since they both coimmunoprecipitated
      with anti-alpha4, anti-beta1, or anti-CD44 antibodies. Immunofluorescence
      analyses confirmed that alpha4beta1 and CD44v colocalized with MMP-9. Binding of
      proMMP-9 inhibited B-CLL cell migration, and this required MMP-9 proteolytic
      activity. Thus, we have identified alpha4beta1 and CD44v as a novel proMMP-9 cell
      surface docking complex and show that cell-associated MMP-9 may regulate B-CLL
      cell migration and arrest.

PMID- 18326821
TI  - CD38 expression in chronic lymphocytic leukemia is regulated by the tumor
      microenvironment.
AB  - Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with a highly
      variable outcome. The prognosis of patients with CLL may be predicted using a
      number of biomarkers, including the level of CD38 expression at the leukemic cell
      surface. This study investigates the hypothesis that CD38 expression by CLL cells
      reflects interactions with nonmalignant cells within pseudofollicles in secondary
      lymphoid tissue where tumor cell proliferation is thought to occur. CD38
      expression is higher in tissues that contain pseudofollicles compared with those
      that do not. In addition, we show that CD38 expression in CLL is dynamic, changes
      in response to contact with activated CD4(+) T cells, and identifies cells that
      are primed to proliferate. Finally, we demonstrate close contact between
      activated CD4(+) T cells and proliferating tumor in primary patient tissue.
      Proliferating tumor cells in lymph nodes express CD38, which is in turn
      associated with an increased number of CD31(+) vascular endothelial cells.
      Although the factors resulting in colocalization of tumor, T cells, and
      endothelium remain unclear, the existence of these cellular clusters may provide
      an explanation for the association between CD38 expression and adverse outcome in
      CLL and suggests novel therapeutic targets.

PMID- 18326822
TI  - Erythropoietin mediates hepcidin expression in hepatocytes through EPOR signaling
      and regulation of C/EBPalpha.
AB  - Hepcidin is the principal iron regulatory hormone, controlling the systemic
      absorption and remobilization of iron from intracellular stores. Recent in vivo
      studies have shown that hepcidin is down-regulated by erythropoiesis, anemia, and
      hypoxia, which meets the need of iron input for erythrocyte production.
      Erythropoietin (EPO) is the primary signal that triggers erythropoiesis in anemic
      and hypoxic conditions. Therefore, a direct involvement of EPO in hepcidin
      regulation can be hypothesized. We report here the regulation of hepcidin
      expression by EPO, in a dose-dependent manner, in freshly isolated mouse
      hepatocytes and in the HepG2 human hepatocyte cell model. The effect is mediated
      through EPOR signaling, since hepcidin mRNA levels are restored by pretreatment
      with an EPOR-blocking antibody. The transcription factor C/EBPalpha showed a
      pattern of expression similar to hepcidin, at the mRNA and protein levels,
      following EPO and anti-EPOR treatments. Chromatin immunoprecipitation experiments
      showed a significant decrease of C/EBPalpha binding to the hepcidin promoter
      after EPO supplementation, suggesting the involvement of this transcription
      factor in the transcriptional response of hepcidin to EPO.

PMID- 18326823
TI  - Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction,
      oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure.
AB  - This study aimed to 1) assess whether substance P (SP) acts via neurokinin (NK)-1
      and NK-2 receptors to stimulate neurogenic inflammation (indicated by formation
      of ICAM-1 expression and oxidative stress) following oil smoke exposure (OSE) in
      rats; and 2) determine if pretreatment with antioxidants ameliorates the
      deleterious effects of OSE. Rats were pretreated with NK-1 receptor antagonist CP
      96345, NK-2 receptor antagonist SR-48968, vitamin C, or catechins. OSE was for 30
      120 min. Rats were killed 0-8 h later. Total lung resistance (RL), airway smooth
      muscle activity (ASMA), lung ICAM-1 expression, neurogenic plasma extravasation
      (via India ink and Evans blue dye), bronchoalveolar lavage fluid SP
      concentrations, and reactive oxygen species formation [via lucigenin- and luminal
      amplified chemiluminescence (CL)] were assessed. Lung histology was performed. SP
      concentrations increased significantly in nonpretreated rats following OSE in a
      dose-dependent manner. RL and total ASMA increased over time after OSE. Vitamin C
      and catechin pretreatments were associated with significantly reduced lucigenin
      CL 2 and 4 h after OSE. Pretreatment with catechins significantly reduced luminal
      CL counts 4 and 8 h after OSE. Evans blue levels were significantly reduced
      following 60 and 120 min of OSE in catechin- and CP-96345-pretreated rats. ICAM-1
      protein expression was significantly decreased in all pretreatment groups after
      OSE. Thickening of the alveolar capillary membrane, focal hemorrhaging,
      interstitial pneumonitis, and peribronchiolar inflammation were apparent in OSE
      lungs. These findings suggest that SP acts via the NK-1 receptor to provoke
      neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in
      rats.

PMID- 18326824
TI  - Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity,
      local vs. mediated effects.
AB  - Reactive species of oxygen and nitrogen have been collectively implicated in
      pulmonary oxygen toxicity, but the contributions of specific molecules are
      unknown. Therefore, we assessed the roles of several reactive species,
      particularly nitric oxide, in pulmonary injury by exposing wild-type mice and
      seven groups of genetically altered mice to >98% O2 at 1, 3, or 4 atmospheres
      absolute. Genetically altered animals included knockouts lacking either neuronal
      nitric oxide synthase (nNOS(-/-)), endothelial nitric oxide synthase (eNOS(-/-)),
      inducible nitric oxide synthase (iNOS(-/-)), extracellular superoxide dismutase
      (SOD3(-/-)), or glutathione peroxidase 1 (GPx1(-/-)), as well as two transgenic
      variants (S1179A and S1179D) having altered eNOS activities. We confirmed our
      earlier finding that normobaric hyperoxia (NBO2) and hyperbaric hyperoxia (HBO2)
      result in at least two distinct but overlapping patterns of pulmonary injury. Our
      new findings are that the role of nitric oxide in the pulmonary pathophysiology
      of hyperoxia depends both on the specific NOS isozyme that is its source and on
      the level of hyperoxia. Thus, iNOS predominates in the etiology of lung injury in
      NBO2, and SOD3 provides an important defense. But in HBO2, nNOS is a major
      contributor to pulmonary injury, whereas eNOS is protective. In addition, we
      demonstrated that nitric oxide derived from nNOS is involved in a neurogenic
      mechanism of HBO2-induced lung injury that is linked to central nervous system
      oxygen toxicity through adrenergic/cholinergic pathways.

PMID- 18326825
TI  - Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is
      associated with increased prostanoid release.
AB  - Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous
      relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase
      (COX), which catalyzes the production of prostanoids, increases this relaxation
      in infant ASM and abolishes age differences, thus suggesting that prostanoids
      reduce relaxation in infant ASM. In this study, we investigated whether
      leukotrienes are also involved in reducing spontaneous relaxation; whether the
      two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous
      relaxation; and whether prostanoid release is developmentally regulated in guinea
      pig ASM. In different age groups, we measured relaxation during and after
      electrical stimulation in tracheal strips as well as prostanoid release from
      tracheal segments. Relaxation was studied in the absence and in the presence of a
      lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1
      inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or
      cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous
      relaxation at any age, thus excluding a role for leukotrienes in this phenomenon.
      Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal
      release of prostanoids was more abundant in tissue from infant animals and
      decreased significantly with age. Thromboxane B2 was the most abundant metabolite
      released at all ages. Electrical stimulation and epithelium removal did not
      affect the age difference in prostanoid release. We conclude that increased basal
      prostanoid release contributes to the reduced spontaneous relaxation in immature
      guinea pig ASM compared with older animals. By regulating ASM relaxation,
      prostanoids may play a role in the airway hyperresponsiveness at a young age.

PMID- 18326826
TI  - Alveolar macrophage activation and an emphysema-like phenotype in adiponectin
      deficient mice.
AB  - Adiponectin is an adipocyte-derived collectin that acts on a wide range of
      tissues including liver, brain, heart, and vascular endothelium. To date, little
      is known about the actions of adiponectin in the lung. Herein, we demonstrate
      that adiponectin is present in lung lining fluid and that adiponectin deficiency
      leads to increases in proinflammatory mediators and an emphysema-like phenotype
      in the mouse lung. Alveolar macrophages from adiponectin-deficient mice
      spontaneously display increased production of tumor necrosis factor-alpha (TNF
      alpha) and matrix metalloproteinase (MMP-12) activity. Consistent with these
      observations, we found that pretreatment of alveolar macrophages with adiponectin
      leads to TNF-alpha and MMP-12 suppression. Together, our findings show that
      adiponectin leads to macrophage suppression in the lung and suggest that
      adiponectin-deficient states may contribute to the pathogenesis of inflammatory
      lung conditions such as emphysema.

PMID- 18326827
TI  - The leaf epidermome of Catharanthus roseus reveals its biochemical
      specialization.
AB  - Catharanthus roseus is the sole commercial source of the monoterpenoid indole
      alkaloids (MIAs), vindoline and catharanthine, components of the commercially
      important anticancer dimers, vinblastine and vincristine. Carborundum abrasion
      technique was used to extract leaf epidermis-enriched mRNA, thus sampling the
      epidermome, or complement, of proteins expressed in the leaf epidermis. Random
      sequencing of the derived cDNA library established 3655 unique ESTs, composed of
      1142 clusters and 2513 singletons. Virtually all known MIA pathway genes were
      found in this remarkable set of ESTs, while only four known genes were found in
      the publicly available Catharanthus EST data set. Several novel MIA pathway
      candidate genes were identified, as demonstrated by the cloning and functional
      characterization of loganic acid O-methyltransferase involved in secologanin
      biosynthesis. The pathways for triterpene biosynthesis were also identified, and
      metabolite analysis showed that oleanane-type triterpenes were localized
      exclusively to the cuticular wax layer. The pathways for flavonoid and very-long
      chain fatty acid biosynthesis were also located in this cell type. The results
      illuminate the biochemical specialization of Catharanthus leaf epidermis for the
      production of multiple classes of metabolites. The value and versatility of this
      EST data set for biochemical and biological analysis of leaf epidermal cells is
      also discussed.

PMID- 18326828
TI  - A MYB transcription factor regulates very-long-chain fatty acid biosynthesis for
      activation of the hypersensitive cell death response in Arabidopsis.
AB  - Plant immune responses to pathogen attack include the hypersensitive response
      (HR), a form of programmed cell death occurring at invasion sites. We previously
      reported on Arabidopsis thaliana MYB30, a transcription factor that acts as a
      positive regulator of a cell death pathway conditioning the HR. Here, we show by
      microarray analyses of Arabidopsis plants misexpressing MYB30 that the genes
      encoding the four enzymes forming the acyl-coA elongase complex are putative
      MYB30 targets. The acyl-coA elongase complex synthesizes very-long-chain fatty
      acids (VLCFAs), and the accumulation of extracellular VLCFA-derived metabolites
      (leaf epidermal wax components) was affected in MYB30 knockout mutant and
      overexpressing lines. In the same lines, a lipid extraction procedure allowing
      high recovery of sphingolipids revealed changes in VLCFA contents that were
      amplified in response to inoculation. Finally, the exacerbated HR phenotype of
      MYB30-overexpressing lines was altered by the loss of function of the acyl-ACP
      thioesterase FATB, which causes severe defects in the supply of fatty acids for
      VLCFA biosynthesis. Based on these findings, we propose a model in which MYB30
      modulates HR via VLCFAs by themselves, or VLCFA derivatives, as cell death
      messengers in plants.

PMID- 18326830
TI  - Twelve-year follow-up on anterior cruciate ligament reconstruction: long-term
      outcomes of prospectively studied osseous and articular injuries.
AB  - BACKGROUND: Although successful at restoring near normal laxity to the knee in
      the short term, anterior cruciate ligament reconstructions have not been shown to
      prevent the development of posttraumatic arthritis. HYPOTHESIS: Bone bruises and
      articular cartilage injuries sustained at the time of initial injury (1991) would
      not resolve. Our secondary hypothesis was that the presence of a bone bruise or
      articular cartilage injury originally identified on magnetic resonance imaging
      would not be associated with long-term outcomes after anterior cruciate ligament
      reconstruction evaluated by the International Knee Documentation Committee
      questionnaire. STUDY DESIGN: Cohort study (prognosis); Level of evidence, 1.
      METHODS: We attempted to contact all patients from an original cohort (N = 54)
      for follow-up evaluation, which included repeat radiographs, magnetic resonance
      images, physical examination, and International Knee Documentation Committee
      questionnaire more than a decade postoperatively. RESULTS: Forty-four patients
      (82% of the original cohort) returned for on-site follow-up. No patient with a
      bone bruise identified on original magnetic resonance imaging had one identified
      at 12-year follow-up. The mean ( +/- SD) International Knee Documentation
      Committee score at follow-up with no bone bruise originally present was 70.6 ( +/
      12.7) versus 70.0 ( +/- 8.1) when a bone bruise was observed (P > .05). No
      consistent association was observed between the presence of an initial articular
      cartilage lesion with a lesion on follow-up magnetic resonance images. The mean (
      +/- SD) International Knee Documentation Committee score at follow-up with no
      articular cartilage injury was 69.0 ( +/- 11.9) versus 72.8 ( +/- 12.0) with
      articular cartilage lesion (P > .05). CONCLUSION: All bone bruises identified in
      our study with magnetic resonance imaging at the time of initial injury had
      resolved at 12-year follow-up. The presence of a bone bruise at the time of
      initial injury did not significantly alter the patient-oriented outcome by
      International Knee Documentation Committee after anterior cruciate ligament
      reconstruction. Additionally, articular cartilage abnormality on magnetic
      resonance imaging did not influence the International Knee Documentation
      Committee score.

PMID- 18326829
TI  - Modulation of nitrosative stress by S-nitrosoglutathione reductase is critical
      for thermotolerance and plant growth in Arabidopsis.
AB  - Nitric oxide (NO) is a key signaling molecule in plants. This analysis of
      Arabidopsis thaliana HOT5 (sensitive to hot temperatures), which is required for
      thermotolerance, uncovers a role of NO in thermotolerance and plant development.
      HOT5 encodes S-nitrosoglutathione reductase (GSNOR), which metabolizes the NO
      adduct S-nitrosoglutathione. Two hot5 missense alleles and two T-DNA insertion,
      protein null alleles were characterized. The missense alleles cannot acclimate to
      heat as dark-grown seedlings but grow normally and can heat-acclimate in the
      light. The null alleles cannot heat-acclimate as light-grown plants and have
      other phenotypes, including failure to grow on nutrient plates, increased
      reproductive shoots, and reduced fertility. The fertility defect of hot5 is due
      to both reduced stamen elongation and male and female fertilization defects. The
      hot5 null alleles show increased nitrate and nitroso species levels, and the heat
      sensitivity of both missense and null alleles is associated with increased NO
      species. Heat sensitivity is enhanced in wild-type and mutant plants by NO
      donors, and the heat sensitivity of hot5 mutants can be rescued by an NO
      scavenger. An NO-overproducing mutant is also defective in thermotolerance.
      Together, our results expand the importance of GSNOR-regulated NO homeostasis to
      abiotic stress and plant development.

PMID- 18326831
TI  - A prospective study of injury patterns in high school pole vaulters.
AB  - BACKGROUND: The pole vault is a track and field event that has witnessed a large
      increase in participants during the past 5 years. Currently there are no
      prospective studies that have evaluated injury patterns in pole vaulters.
      OBJECTIVES: To determine the injury rate and to describe injury patterns in high
      school pole vaulters. STUDY DESIGN: Descriptive epidemiological study. METHODS:
      This was a prospective cohort study of 140 Wisconsin high school athletes who
      participated in pole vaulting during the 2005 and 2006 track and field seasons.
      Baseline athlete information was obtained at the beginning of each season. When
      an injury occurred, an injury report form was completed to document diagnosis and
      circumstances of the incident. Injury rates were expressed as injuries per 100
      athletes per season as well as injuries per 1000 athletic exposures. Risk factors
      were analyzed by calculating relative risks for baseline athlete variables.
      RESULTS: The injury rates were 26.4 injuries per 100 athletes per season (95%
      confidence interval, 18.6-36.4) and 7.1 injuries per 1000 athletic exposures (95%
      confidence interval, 5.0-9.8). Trauma to the lower extremities accounted for
      71.5% of injuries. The most common injury types were ligament sprains (31.6%).
      Landing incorrectly was the most frequent mechanism of injury (26.3%). A history
      of pole-vault injury was associated with increased risk of injury (relative risk,
      2.4; 95% confidence interval, 1.4-4.1). CONCLUSION: Injuries are common in young
      vaulters. Injury mechanisms indicate that many could be avoided by using proper
      technique, particularly during the landing phase. Coaches should focus on
      vaulters with prior injuries to identify risky behavior and to help correct poor
      technique.

PMID- 18326832
TI  - Can platelet-rich plasma enhance tendon repair? A cell culture study.
AB  - BACKGROUND: Autologous platelet-rich plasma (PRP) application appears to improve
      tendon healing in traumatic tendon injuries, but basic knowledge of how PRP
      promotes tendon repair is needed. HYPOTHESIS: Platelet-rich plasma has a positive
      effect on cell proliferation and collagen production and induces the production
      of matrix-degrading enzymes and endogenous growth factors by human tenocytes.
      STUDY DESIGN: Controlled laboratory study. METHODS: Human tenocytes were cultured
      14 days in 2% fetal calf serum medium complemented with 0%, 10%, or 20% vol/vol
      platelet-rich clot releasate ([PRCR] the active releasate of PRP) or platelet
      poor clot releasate (PPCR). At day 4, 7, and 14, cell amount, total collagen, and
      gene expression of collagen I alpha 1 (COL1) and III alpha 1 (COL3), matrix
      metalloproteinases ([MMPs] MMP1, MMP3, and MMP13), vascular endothelial-derived
      growth factor (VEGF)-A, and transforming growth factor (TGF)-beta1 were analyzed.
      RESULTS: Platelet numbers in PRP increased to 2.55 times baseline. Growth-factor
      concentrations of VEGF and platelet-derived growth factor (PDGF)-BB were higher
      in PRCR than PPCR. Both PRCR and PPCR increased cell number and total collagen,
      whereas they decreased gene expression of COL1 and COL3 without affecting the
      COL3/COL1 ratio. PRCR, but not PPCR, showed upregulation of MMP1 and MMP3
      expression. Matrix metalloproteinase 13 expression was not altered by either
      treatment. PRCR increased VEGF-A expression at all time points and TGF-beta1
      expression at day 4. CONCLUSION: In human tenocyte cultures, PRCR, but also PPCR,
      stimulates cell proliferation and total collagen production. PRCR, but not PPCR,
      slightly increases the expression of matrix-degrading enzymes and endogenous
      growth factors. CLINICAL RELEVANCE: In vivo use of PRP, but also of PPP to a
      certain extent, in tendon injuries might accelerate the catabolic demarcation of
      traumatically injured tendon matrices and promote angiogenesis and formation of a
      fibrovascular callus. Whether this will also be beneficial for degenerative
      tendinopathies remains to be elucidated.

PMID- 18326833
TI  - The effects of generalized joint laxity on risk of anterior cruciate ligament
      injury in young female athletes.
AB  - BACKGROUND: Women who participate in high-risk sports suffer anterior cruciate
      ligament injury at a 4- to 6-fold greater rate than men. PURPOSE: To
      prospectively determine if female athletes with decreased passive knee joint
      restraint (greater joint laxity) and greater side-to-side differences in knee
      laxity would be at increased risk of anterior cruciate ligament injury. STUDY
      DESIGN: Case control study; Level of evidence, 3. METHODS: From 1558 female
      soccer and basketball players who were prospectively screened, 19 went on to tear
      their anterior cruciate ligaments. Four height- and mass-matched control subjects
      were selected from the uninjured screened athletes for comparison with each of
      the 19 injured subjects, making a total of 95 subjects (19 injured; 76
      uninjured). Generalized joint-laxity tests and anterior-posterior tibiofemoral
      translation were quantified using the CompuKT knee arthrometer. A multivariable
      logistic regression model was constructed to determine predictors of anterior
      cruciate ligament injury status from recorded laxity measures. RESULTS: A
      multivariable logistic regression model (chi-square = 18.6; P = .002) used the
      independent variables laxity measures of knee hyperextension (P = .02), wrist and
      thumb to forearm opposition (P = .80), fifth-finger hyperextension > 90 degrees
      (P = .71), side-to-side differences in anterior-posterior tibiofemoral
      translation (P = .002), and prior knee injury (P = .22) to predict anterior
      cruciate ligament-injury status. The validated C statistic, or validated area
      under the receiver operating characteristic curve, was 0.72. For every 1.3-mm
      increase in side-to-side differences in anterior-posterior knee displacement, the
      odds of anterior cruciate ligament-injured status increased 4-fold (95%
      confidence interval, 1.68-9.69). A positive measure of knee hyperextension
      increased the odds of anterior cruciate ligament-injured status 5-fold (95%
      confidence interval, 1.24-18.44). CONCLUSION: The current results indicate that
      increased knee-laxity measures may contribute to increased risk of anterior
      cruciate ligament injury. The methods to quantify knee joint laxity in this
      report may be used in conjunction with measures of neuromuscular control of the
      knee joint to identify high-risk female athletes with high accuracy. Once high
      risk female athletes are identified, they may be targeted to the appropriate
      interventions to reduce injury risk.

PMID- 18326834
TI  - Intrasubstance stretch tear of a preadolescent patellar tendon with
      reconstruction using autogenous hamstrings.

PMID- 18326835
TI  - Assessing how many blood cultures are needed for detecting bloodstream
      infections.

PMID- 18326836
TI  - Clostridium difficile PCR ribotype 078: an emerging strain in humans and in pigs?

PMID- 18326837
TI  - Serotyping and population genetics of invasive Haemophilus influenzae.

PMID- 18326838
TI  - Regulation of Dlx5 and Dlx6 gene expression by p63 is involved in EEC and SHFM
      congenital limb defects.
AB  - The congenital malformation Split Hand-Foot Malformation (SHFM, or ectrodactyly)
      is characterized by a medial cleft of hands and feet, and missing central
      fingers. Five genetically distinct forms are known in humans; the most common
      (type-I) is linked to deletions of DSS1 and the distalless-related homeogenes
      DLX5 and DLX6. As Dlx5;Dlx6 double-knockout mice show a SHFM-like phenotype, the
      human orthologs are believed to be the disease genes. SHFM-IV and Ectrodactyly
      Ectodermal dysplasia-Cleft lip (EEC) are caused by mutations in p63, an ectoderm
      specific p53-related transcription factor. The similarity in the limb phenotype
      of different forms of SHFM may underlie the existence of a regulatory cascade
      involving the disease genes. Here, we show that p63 and Dlx proteins colocalize
      in the nuclei of the apical ectodermal ridge (AER). In homozygous p63- (null) and
      p63EEC (R279H) mutant limbs, the AER fails to stratify and the expression of four
      Dlx genes is strongly reduced; interestingly, the p63+/EEC and p63+/- hindlimbs,
      which develop normally and have a normally stratified AER, show reduced Dlx gene
      expression. The p63+/EEC mutation combined with an incomplete loss of Dlx5 and
      Dlx6 alleles leads to severe limb phenotypes, which are not observed in mice with
      either mutation alone. In vitro, DeltaNp63alpha induces transcription from the
      Dlx5 and Dlx6 promoters, an activity abolished by EEC and SHFM-IV mutations, but
      not by Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) mutations. ChIP
      analysis shows that p63 is directly associated with the Dlx5 and Dlx6 promoters.
      Thus, our data strongly implicate p63 and the Dlx5-Dlx6 locus in a pathway
      relevant in the aetio-pathogenesis of SHFM.

PMID- 18326840
TI  - Bluetongue in the United Kingdom and northern Europe in 2007 and key issues for
      2008.
AB  - As predicted, bluetongue arrived in the UK in 2007. Here, John Gloster and
      colleagues investigate the meteorological parameters that allowed this incursion
      into the UK and discuss key issues related to the disease's possible re
      establishment in 2008.

PMID- 18326841
TI  - Retrospective analysis of exploratory laparotomies in 192 Andalusian horses and
      276 horses of other breeds.
AB  - The medical records of 468 horses that underwent 490 exploratory laparotomies for
      the correction of gastrointestinal diseases were reviewed to search for
      differences between Andalusian horses and other breeds. The seasonal distribution
      of surgical colics and their outcome and complications were also investigated.
      Bivariant analysis was used to compare the horses' age, gender and breed with the
      type of surgery, the bowel affected and the type of colic, and all these
      variables were compared in relation to euthanasia during surgery, complications,
      short-term survival and seasonal distribution. A total of 405 horses survived the
      surgery and 329 were discharged from the hospital. Horses less than one year old
      had better short-term survival than older horses. Andalusian horses suffered more
      inguinal hernias than the other breeds and were more prone to suffer laminitis as
      a complication. Colic surgery and inguinal hernias were also more common in the
      summer.

PMID- 18326842
TI  - Epidemic of diarrhoea caused by porcine epidemic diarrhoea virus in Italy.
AB  - There was an epidemic of diarrhoea affecting pigs of all ages in Italy between
      May 2005 and June 2006. In 63 herds the cause was confirmed as porcine epidemic
      diarrhoea virus by electron microscopy, immunoelectron microscopy, pcr and
      serology. Watery diarrhoea without mucus and blood was usually associated with a
      reduction of feed consumption. In farrowing-to-weaning herds, diarrhoea affected
      the sows and suckling piglets, and the mortality in newborn piglets was up to 34
      per cent. In growers and fatteners the morbidity ranged from 20 to 80 per cent,
      but there was either no mortality or it was very low. Depending on the size of
      the herd and the type of operation, the clinical disease lasted for weeks or
      months.

PMID- 18326843
TI  - Ultrasonographic findings in cows with right displacement of the abomasum and
      abomasal volvulus.
AB  - Seventeen cows with right displacement of the abomasum (rda) without abomasal
      volvulus, nine cows with abomasal volvulus and 10 clinically healthy cows were
      examined ultrasonographically. A 5.0 MHz transducer was used to scan the eighth
      to 12th intercostal spaces and the cranial and caudal aspects of the flank on the
      right side. The position, size and dorsal and ventral margins of the abomasum
      were determined at each imaging position. In both groups of diseased cows, the
      ventral abomasum contained fluid ingesta, which appeared hypoechogenic with
      diffuse echogenic stippling. The abomasal folds could be seen clearly as
      echogenic sickle-shaped structures within the ingesta. The dorsal abomasal gas
      cap varied in size and was characterised by reverberation artefacts, which
      appeared as echogenic lines running parallel to the body surface. Compared with
      the healthy cows, the abomasum was larger and located significantly closer to the
      midline of the dorsum in both groups of cows. Compared with the cows with rda,
      the abomasum in the cows with abomasal volvulus was significantly smaller in the
      eighth intercostal space and significantly larger in the 11th intercostal space.
      It was not possible to differentiate between rda and abomasal volvulus on the
      basis of the ultrasonographic findings.

PMID- 18326844
TI  - Prospects for rapid diagnosis of foot-and-mouth disease in the field using
      reverse transcriptase-PCR.

PMID- 18326845
TI  - Mass wildlife mortality due to cyanobacteria in the Donana National Park, Spain.

PMID- 18326846
TI  - Naturally occurring intestinal lesions in three alpacas (Vicugna pacos) caused by
      attaching and effacing Escherichia coli.

PMID- 18326848
TI  - Diurnal activity of potential bluetongue vectors in northern Europe.

PMID- 18326849
TI  - Syringomyelia in cavalier King Charles spaniels.

PMID- 18326850
TI  - Respiratory disease in lambs.

PMID- 18326851
TI  - Mortality in patients with atrial fibrillation: improving or not?

PMID- 18326852
TI  - Mortality in patients with atrial fibrillation has significantly decreased during
      the last three decades: 35 years of follow-up in 1627 pacemaker patients.
AB  - AIM: The impact of atrial fibrillation (AF) on mortality is not fully understood.
      We therefore sought to investigate long-term effects of AF on mortality in
      patients with the need for pacemaker (PM) therapy. METHODS AND RESULTS: A total
      of 1627 PM recipients with AF at implantation were followed in a single-centre,
      longitudinal study for up to 35 years. Baseline factors affecting survival and
      long-term follow-up were analysed. A total of 7362 patient-years of follow-up (PM
      implanted between 1971 and 2000, followed until 31 December 31 2005) were
      analysed. Female PM recipients lived significantly longer than male (P = 0.025;
      mean survival 91.9 vs. 72.1 months) despite older age at time of inclusion. Mean
      survival times almost doubled for patients implanted in the last decade, with
      139.8 months in the nineties vs. 66.8 months in the seventies and 75.7 months in
      the eighties (P < 0.001). Male gender, age at implantation, non-syncopal
      bradycardia, and decade of implantation influenced survival. CONCLUSION: Life
      expectancy in AF patients after PM implantation has doubled within the last three
      decades, with a mean survival in the overall population of 7.6 years for women
      and 6.0 years for men. Survival is influenced by several simple baseline
      characteristics, which may help to identify patients with very long survival
      times.

PMID- 18326853
TI  - Costs of atrial fibrillation in five European countries: results from the Euro
      Heart Survey on atrial fibrillation.
AB  - AIMS: To estimate costs of admission and costs incurred on an annual basis by
      patients with atrial fibrillation (AF) in Greece, Italy, Poland, Spain, and the
      Netherlands. METHODS AND RESULTS: The Euro Heart Survey on AF enrolled 5333
      patients with AF in 35 European countries in 2003 and 2004. This was a bottom-up
      cost study conducted for the five largest contributors in terms of patients
      enrolled. Quantities of resource use during the enrolment admission and during 1
      year follow-up were inferred from survey data and multiplied by national unit
      costs in order to estimate per patient costs associated with AF for each country.
      Mean costs of inpatient admission of an AF patient were estimated at euro1363,
      euro5252, euro2322, euro6360, and euro6445 and mean costs incurred on an annual
      basis at euro1507, euro3225, euro1010, euro2315, and euro2328 in Greece, Italy,
      Poland, Spain, and the Netherlands, respectively. Inpatient care and
      interventional procedures were identified as the main drivers of costs,
      accounting for more than 70% of total annual costs in all five countries.
      CONCLUSION: Estimates of the economic burden posed by AF are critical in light of
      the increasing importance of AF as a public health problem.

PMID- 18326854
TI  - Profound effect of study design factors on ventilator-associated pneumonia
      incidence of prevention studies: benchmarking the literature experience.
AB  - BACKGROUND: The ventilator-associated pneumonia incident proportion (VAP-IP) is
      highly variable among control groups of studies of methods for its prevention.
      The objective here is to develop and validate a literature-derived benchmark
      against which these groups can be profiled. METHODS: A literature search yielded
      95 cohort groups and control and intervention groups of 150 studies of either non
      antimicrobial or antimicrobial methods of VAP prevention. The 95 cohort groups
      comprise a benchmark set (30 groups), from which the reference funnel plot (RFP)
      was derived, and a search set (65 groups), against which the benchmark was
      validated. The VAP-IP data of the benchmark set were found in five published
      systematic reviews, whereas the VAP-IP data of the search set were abstracted
      directly from the literature. FINDINGS: Among the 95 cohort groups, the VAP-IP of
      groups with size >399 was significantly lower than the VAP-IP of smaller groups.
      Compared with the RFP, 15 of 51 (29%) control groups from studies of
      antimicrobial methods of VAP prevention with concurrent design were high outlier
      versus 2 of 110 (2%) control groups from other types of study design (P < 0.001).
      There were only 22 (14%) outlier groups, all low outlier, among the 162
      intervention groups. CONCLUSIONS: Study design factors such as concurrency and
      study size have potentially greater influence on the VAP-IP than do the VAP
      prevention methods under study. The outlier status of control groups were
      inapparent in the individual studies and the meta-analyses and yet would have
      confounded the estimates of treatment effect.

PMID- 18326855
TI  - Antimicrobial susceptibility of periodontopathogenic bacteria.
AB  - OBJECTIVES: The aim of this study was to evaluate the resistance profiles of
      Aggregatibacter (Actinobacillus) actinomycetemcomitans, Porphyromonas gingivalis
      and Prevotella intermedia/Prevotella nigrescens and to detect possible changes in
      antibiotic resistance over the time period of 1991-2005. METHODS: A.
      actinomycetemcomitans (125 strains), P. gingivalis (152 strains) and P.
      intermedia/P. nigrescens (326 strains) isolated during the years 1991-2005 were
      tested for their susceptibility to amoxicillin/clavulanic acid, clindamycin,
      metronidazole, phenoxymethylpenicillin and tetracycline using the Etest. RESULTS:
      No antibiotic resistance was detected in P. gingivalis, whereas a few isolates of
      P. intermedia were not susceptible to clindamycin (0.9%), phenoxymethylpenicillin
      (13.5%) or tetracycline (12.6%). Amoxicillin/clavulanic acid, tetracycline and
      metronidazole were the most effective antibiotics against A.
      actinomycetemcomitans with 0%, 0.8% and 20.8% non-susceptible isolates,
      respectively. However, 88% of the A. actinomycetemcomitans isolates were non
      susceptible to phenoxymethylpenicillin and 88% to clindamycin. When strains
      isolated in the years 1991-94 were compared with those isolated in the years 2001
      04, there was no statistically significant difference in the percentage of A.
      actinomycetemcomitans strains non-susceptible to clindamycin, metronidazole or
      phenoxymethylpenicillin, or in the percentage of P. intermedia strains non
      susceptible to phenoxymethylpenicillin or tetracycline (P > 0.4 each).
      CONCLUSIONS: Increasing antibiotic resistances in periodontopathogenic bacteria
      are not yet a problem in the Northern part of Switzerland.

PMID- 18326856
TI  - Activity of BAL 4815 against filamentous fungi.
AB  - OBJECTIVES: BAL 4815 is a new antifungal drug and it is the active component of
      the antifungal triazole BAL 8557 (the water-soluble precursor). We studied the in
      vitro fungistatic and fungicidal activities of BAL 4815 against 103 clinical
      isolates of filamentous fungi, including 51 isolates of Aspergillus spp. and 52
      isolates of non-Aspergillus filamentous fungi. METHODS: We evaluated the in vitro
      activity of BAL 4815 against 51 isolates of Aspergillus spp., 20 isolates of
      dematiaceous fungi, 18 isolates of hyaline Hyphomycetes and 14 isolates of
      Zygomycetes. MICs were determined following the CLSI M38-A broth microdilution
      method, using RPMI 1640 medium buffered to pH 7.0 with MOPS. Microdilution plates
      were incubated at 35 degrees C and read at 24 and 48 h (Mucorales were read at 24
      h). Minimal fungicidal concentrations were also determined. RESULTS: For all
      isolates, geometric mean MICs, MIC(50)s, MIC(90)s and MIC ranges (mg/L) were:
      Aspergillus spp., 1.67, 2, 4 and 0.5-4; dematiaceous fungi, 1.62, 1, >8 and 0.03
      to >8; hyaline Hyphomycetes, 2.41, 2, >8 and 0.03 to >8; and Zygomycetes, 6.81,
      8, >8 and 0.03 to >8. Differences in susceptibility between genera were noted.
      Scedosporium prolificans, Fusarium spp., Mucor spp. and Rhizopus spp. (MIC(90) >
      8 mg/L) were less susceptible than Aspergillus spp. (MIC(90) = 4 mg/L).
      CONCLUSIONS: BAL 4815 has excellent in vitro activity against Aspergillus spp.
      and variable activity against other filamentous fungi.

PMID- 18326857
TI  - Hyaluronan constitutively regulates activation of COX-2-mediated cell survival
      activity in intestinal epithelial and colon carcinoma cells.
AB  - Hyaluronan is a major component of the pericellular matrix surrounding tumor
      cells, including colon carcinomas. Elevated cycooxygenase-2 levels have been
      implicated in several malignant properties of colon cancer. We now show for the
      first time a strong link between hyaluronan-CD44 interaction and cyclooxygenase-2
      in colon cancer cells. First, we have shown that increased expression of
      hyaluronan synthase-2 induces malignant cell properties, including increased
      proliferation, anchorage-independent growth, and epithelial-mesenchymal
      transition in HIEC6 cells. Second, constitutive hyaluronan-CD44 interaction
      stimulates a signaling pathway involving ErbB2, phosphoinositide 3-kinase/AKT,
      beta-catenin, and cyclooxygenase-2/prostaglandin E(2) in HCA7 colon carcinoma
      cells. Third, the HA/CD44-activated ErbB2 --> phosphoinositide 3-kinase/AKT -->
      beta-catenin pathway stimulates cell survival/cell proliferation through COX-2
      induction in hyaluronan-overexpressing HIEC6 cells and in HCA7 cells. Fourth,
      perturbation of hyaluronan-CD44 interaction by hyaluronan oligomers or CD44
      silencing RNA decreases cyclooxygenase-2 expression and enzyme activity, and
      inhibition of cyclooxygenase-2 decreases hyaluronan production suggesting the
      possibility of an amplifying positive feedback loop between hyaluronan and
      cyclooxygenase-2. We conclude that hyaluronan is an important endogenous
      regulator of colon cancer cell survival properties and that cyclooxygenase-2 is a
      major mediator of these hyaluronan-induced effects. Defining hyaluronan-dependent
      cyclooxygenase-2/prostaglandin E(2)-associated signaling pathways will provide a
      platform for developing novel therapeutic approaches for colon cancer.

PMID- 18326858
TI  - The MutSalpha-proliferating cell nuclear antigen interaction in human DNA
      mismatch repair.
AB  - We have examined the interaction parameters, conformation, and functional
      significance of the human MutSalpha(.) proliferating cell nuclear antigen (PCNA)
      complex in mismatch repair. The two proteins associate with a 1:1 stoichiometry
      and a K(D) of 0.7 microm in the absence or presence of heteroduplex DNA. PCNA
      does not influence the affinity of MutSalpha for a mismatch, and mismatch-bound
      MutSalpha binds PCNA. Small angle x-ray scattering studies have established the
      molecular parameters of the complex, which are consistent with an elongated
      conformation in which the two proteins associate in an end-to-end fashion in a
      manner that does not involve an extended unstructured tether, as has been
      proposed for yeast MutSalpha and PCNA ( Shell, S. S., Putnam, C. D., and
      Kolodner, R. D. (2007) Mol. Cell 26, 565-578 ). MutSalpha variants lacking the
      PCNA interaction motif are functional in 3'- or 5'-directed mismatch-provoked
      excision, but display a partial defect in 5'-directed mismatch repair. This
      finding is consistent with the modest mutability conferred by inactivation of the
      MutSalpha PCNA interaction motif and suggests that interaction of the replication
      clamp with other repair protein(s) accounts for the essential role of PCNA in
      MutSalpha-dependent mismatch repair.

PMID- 18326859
TI  - Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.
AB  - Disorders of wound healing characterized by impaired or delayed re
      epithelialization are a serious medical problem. These conditions affect many
      tissues, are painful, and are difficult to treat. In this study using cornea as a
      model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as
      intestinal trefoil factor) in re-epithelialization of wounds. In two different
      models of corneal wound healing, alkali- and laser-induced corneal wounding, we
      analyzed the wound healing process in in vivo as well as in combined in vivo/in
      vitro model in wild type (Tff3(+)(/)(+)) and Tff3-deficient (Tff3(-)(/)(-)) mice.
      Furthermore, we topically applied different concentrations of recombinant human
      TFF3 (rTFF3) peptide on the wounded cornea to determine the efficacy of rTFF3 on
      corneal wound healing. We found that Tff3 peptide is not expressed in intact
      corneal epithelium, but its expression is extensively up-regulated after
      epithelial injury. Re-epithelialization of corneal wounds in Tff3(-/-) mice is
      significantly prolonged in comparison to Tff3(+/+) mice. In addition, exogenous
      application of rTFF3 to the alkali-induced corneal wounds accelerates
      significantly in in vivo and in combined in vivo/in vitro model wound healing in
      Tff3(+/+) and Tff3(-/-) mice. These findings reveal a pivotal role for Tff3 in
      corneal wound healing mechanism and have broad implications for developing novel
      therapeutic strategies for treating nonhealing wounds.

PMID- 18326860
TI  - TLR4 signaling is coupled to SRC family kinase activation, tyrosine
      phosphorylation of zonula adherens proteins, and opening of the paracellular
      pathway in human lung microvascular endothelia.
AB  - Bacterial lipopolysaccharide (LPS) is a key mediator in the vascular leak
      syndromes associated with Gram-negative bacterial infections. LPS opens the
      paracellular pathway in pulmonary vascular endothelia through protein tyrosine
      phosphorylation. We now have identified the protein-tyrosine kinases (PTKs) and
      their substrates required for LPS-induced protein tyrosine phosphorylation and
      opening of the paracellular pathway in human lung microvascular endothelial cells
      (HMVEC-Ls). LPS disrupted barrier integrity in a dose- and time-dependent manner,
      and prior broad spectrum PTK inhibition was protective. LPS increased tyrosine
      phosphorylation of zonula adherens proteins, VE-cadherin, gamma-catenin, and
      p120(ctn). Two SRC family PTK (SFK)-selective inhibitors, PP2 and SU6656, blocked
      LPS-induced increments in tyrosine phosphorylation of VE-cadherin and p120(ctn)
      and paracellular permeability. In HMVEC-Ls, c-SRC, YES, FYN, and LYN were
      expressed at both mRNA and protein levels. Selective small interfering RNA
      induced knockdown of c-SRC, FYN, or YES diminished LPS-induced SRC Tyr(416)
      phosphorylation, tyrosine phosphorylation of VE-cadherin and p120(ctn), and
      barrier disruption, whereas knockdown of LYN did not. For VE-cadherin
      phosphorylation, knockdown of either c-SRC or FYN provided total protection,
      whereas YES knockdown was only partially protective. For p120(ctn)
      phosphorylation, knockdown of FYN, c-SRC, or YES each provided comparable but
      partial protection. Toll-like receptor 4 (TLR4) was expressed both on the surface
      and intracellular compartment of HMVEC-Ls. Prior knockdown of TLR4 blocked both
      LPS-induced SFK activation and barrier disruption. These data indicate that LPS
      recognition by TLR4 activates the SFKs, c-SRC, FYN, and YES, which, in turn,
      contribute to tyrosine phosphorylation of zonula adherens proteins to open the
      endothelial paracellular pathway.

PMID- 18326861
TI  - Month of birth and offspring count of women: data from the Southern hemisphere.
AB  - BACKGROUND: Several studies indicate that the month of birth affects later
      reproductive output of women in the Northern hemisphere. METHODS: To investigate
      whether a comparable but time-shifted effect is also present in the Southern
      hemisphere where the seasonal variation of the environment is reversed, we
      analysed the association between birth month and offspring count in post
      reproductive New Zealand women. We further examined whether this association
      differed with the hemisphere of birth as well as the socio-economic background.
      RESULTS: We find that the association between birth month and offspring count of
      New Zealand women born in the Southern, albeit not Northern, hemisphere is a
      mirror image of the pattern reported from Austrian women: on average, women born
      during the Southern hemisphere summer months have fewer children than women born
      in winter. This association is highly significant within the lowest family income
      category but insignificant within higher family income categories. CONCLUSIONS:
      This study provides evidence for a causal link between the seasonality of the
      environment during the pre- and perinatal period and offspring count of women. It
      further indicates that the main contribution of the birth month effect found in
      the present study comes from the lowest family income category.

PMID- 18326862
TI  - Two circular chromosomes of unequal copy number make up the mitochondrial genome
      of the rotifer Brachionus plicatilis.
AB  - The monogonont rotifer Brachionus plicatilis is an emerging model system for a
      diverse array of questions in limnological ecosystem dynamics, the evolution of
      sexual recombination, cryptic speciation, and the phylogeny of basal metazoans.
      We sequenced the complete mitochondrial genome of B. plicatilis sensu strictu
      NH1L and found that it is composed of 2 circular chromosomes, designated mtDNA-I
      (11,153 bp) and mtDNA-II (12,672 bp). Hybridization to DNA isolated from
      mitochondria demonstrated that mtDNA-I is present at 4 times the copy number of
      mtDNA-II. The only nucleotide similarity between the 2 chromosomes is a 4.9-kbp
      region of 99.5% identity including a transfer RNA (tRNA) gene and an extensive
      noncoding region that contains putative D-loop and control sequence. The mtDNA-I
      chromosome encodes 4 proteins (ATP6, COB, NAD1, and NAD2), 13 tRNAs, and the
      large and small subunit ribosomal RNAs; mtDNA-II encodes 8 proteins (COX1-3, NAD3
      6, and NAD4L) and 9 tRNAs. Gene order is not conserved between B. plicatilis and
      its closest relative with a sequenced mitochondrial genome, the acanthocephalan
      Leptorhynchoides thecatus, or other sequenced mitochondrial genomes. Polymerase
      chain reaction assays and Southern hybridization to DNA from 18 strains of
      Brachionus suggest that the 2-chromosome structure has been stable for millions
      of years. The novel organization of the B. plicatilis mitochondrial genome into 2
      nearly equal chromosomes of 4-fold different copy number may provide insight into
      the evolution of metazoan mitochondria and the phylogenetics of rotifers and
      other basal animal phyla.

PMID- 18326863
TI  - Application of CD27 as a marker for distinguishing human NK cell subsets.
AB  - It has long been recognized that human NK cells can be divided into two
      phenotypically and functionally distinct subsets, based on their levels of
      expression of CD56. We recently found that CD27 distinguishes subsets of mature
      mouse NK cells. Here we report that CD27 can be used as a marker to discriminate
      human NK cell subsets. The majority of peripheral blood human NK cells were
      CD27(lo)/CD56(dim) NK cells, whereas the minor CD27(hi) NK cell population
      correspondingly displayed a CD56(bright) phenotype. Distinctions between CD27(lo)
      and CD27(hi) NK cells in their receptor expression and typical NK cell functions
      such as cytotoxicity and cytokine production can be easily delineated. Therefore,
      we propose the dual use of CD27 and CD56 as maturation/subset markers for human
      NK cells. The identification of CD27 subsets in both mice and humans will allow
      more accurate projections of the role of NK cell subsets in murine models of
      human pathologies where NK cells are involved.

PMID- 18326864
TI  - Development of abiotic stress tolerance via bZIP-type transcription factor LIP19
      in common wheat.
AB  - Cereal lip19 genes encoding bZIP-type transcription factors are assumed to play a
      regulatory role in gene expression during the cold acclimation process. However,
      no direct evidence shows an association of LIP19-type bZIPs with stress tolerance
      or activation of stress-responsive Cor/Lea genes. To understand the molecular
      basis of development of abiotic stress tolerance through the LIP19 transcription
      factor, a wheat lip19 homologue, Wlip19, was isolated and characterized. Wlip19
      expression was activated by low temperature in seedlings and was higher in a
      freezing-tolerant cultivar than in a freezing-sensitive one. Wlip19 also
      responded to drought and exogenous ABA treatment. Wlip19-expressing transgenic
      tobacco showed a significant increase in abiotic stress tolerance, especially
      freezing tolerance. Expression of a GUS reporter gene under the control of
      promoter sequences of four wheat Cor/Lea genes, Wdhn13, Wrab17, Wrab18, and
      Wrab19, was enhanced by Wlip19 expression in wheat callus and tobacco plants.
      These results indicate that WLIP19 acts as a transcriptional regulator of Cor/Lea
      genes in the development of abiotic stress tolerance. Moreover, direct protein
      protein interaction between WLIP19 and a wheat OBF1 homologue TaOBF1, another
      bZIP-type transcription factor, was observed, suggesting that this interaction is
      conserved in cereals.

PMID- 18326865
TI  - Bird-pollinated flowers in an evolutionary and molecular context.
AB  - Evolutionary shifts to bird pollination (ornithophily) have occurred
      independently in many lineages of flowering plants. This shift affects many
      floral features, particularly those responsible for the attraction of birds,
      deterrence of illegitimate flower visitors (particularly bees), protection from
      vigorous foraging by birds, and accurate placement of pollen on bird's bodies.
      Red coloration appears to play a major role in both bee-deterrence and bird
      attraction. Other mechanisms of bird-attraction include the production of
      abundant dilute nectar and the provision of secondary perches (for non-hovering
      birds). As a result of selection for similar phenotypic traits in unrelated bird
      pollinated species, a floral syndrome of ornithophily can be recognized, and this
      review surveys the component floral traits. The strong convergent evolution
      evident in bird-pollinated flowers raises a question about the nature of the
      genetic mechanisms underlying such transitions and whether the same gene systems
      are involved in most cases. As yet there is too little information to answer this
      question. However, some promising model systems have been developed that include
      closely related bee and bird-pollinated flowers, such as Ipomoea, Mimulus, and
      Lotus. Recent studies of floral developmental genetics have identified numerous
      genes important in the development of the floral phenotype, which are also
      potential candidates for involvement in shifts between bee-pollination and bird
      pollination. As more whole-genome information becomes available, progress should
      be rapid.

PMID- 18326866
TI  - ECVAM retrospective validation of in vitro micronucleus test (MNT).
AB  - In the past decade several studies comparing the in vitro chromosome aberration
      test (CAT) and the in vitro micronucleus test (MNT) were performed. A high
      correlation was observed in each of the studies (>85%); however, no formal
      validation for the micronucleus in vitro assay had been carried out. Therefore, a
      working group was established by the European Centre for the Validation of
      Alternative Methods (ECVAM) to perform a retrospective validation of the existing
      data, in order to evaluate the validity of the in vitro MNT on the basis of the
      modular validation approach. The primary focus of this retrospective validation
      was on the evaluation of the potential of the in vitro MNT as alternative to the
      standard in vitro CAT. The working group evaluated, in a first step, the
      available published data and came to the conclusion that two studies [German ring
      trial, von der Hude, W., Kalweit, S., Engelhardt, G. et al. (2000) In-vitro
      micronucleus assay with Chinese hamster V79 cells: results of a collaborative
      study with 26 chemicals. Mutat. Res., 468, 137-163, and SFTG International
      Collaborative Study, Lorge, E., Thybaud, V., Aardema, M., Oliver, J., Wataka, A.,
      Lorenzon, G. and Marzin, D. (2006) SFTG International Collaborative Study on in
      vitro micronucleus test I. General conditions and overall conclusions of the
      study. Mutat. Res., 607, 13-36] met the criteria for a retrospective validation
      according to the criteria previously defined by the working group. These two
      studies were evaluated in depth (including the reanalysis of raw data) and
      provided the information required for assessing the reliability (reproducibility)
      of the test. For the assessment of the concordance between the in vitro MNT and
      the in vitro CAT, additional published data were considered. Based on this
      retrospective validation, the ECVAM Validation Management Team concluded that the
      in vitro MNT is reliable and relevant and can therefore be used as an alternative
      method to the in vitro CAT. Following peer review, these conclusions were
      formally endorsed by the ECVAM Scientific Advisory Committee.

PMID- 18326867
TI  - The comet assay in human biomonitoring: gene-environment interactions.
AB  - The comet assay is the method of choice for measuring DNA damage, of various
      sorts, in human cells such as lymphocytes obtained in the course of population
      based studies of environmental and occupational exposure to different genotoxic
      agents, including radiation, chemicals and oxidative stress. It is noted for its
      versatility and the breadth of its possible applications. In terms of simplicity,
      cost, small amount of material required, sensitivity and reliability, the comet
      assay in its various modifications has few serious competitors. When standardized
      and validated, the comet assay can provide invaluable information in the areas of
      hazard identification and risk assessment of environmental and occupational
      exposure, diseases linked with oxidative stress (e.g. diabetes and cardiovascular
      disease), nutrition, monitoring the effectiveness of medical treatment and
      investigating individual variation in response to DNA damage that may reflect
      genetic or environmental influences. The information obtained could lead to
      individual advice on lifestyle changes to promote health and especially on
      relative risks of genotoxic exposure to environmental pollution.

PMID- 18326868
TI  - Variation in assessment of oxidatively damaged DNA in mononuclear blood cells by
      the comet assay with visual scoring.
AB  - The comet assay is popular for assessments of genotoxicity, but the comparison of
      results between studies is challenging because of differences in experimental
      procedures and reports of DNA damage in different units. We investigated the
      variation of DNA damage in mononuclear blood cells (MNBCs) measured by the comet
      assay with focus on the variation related to alkaline unwinding and
      electrophoresis time, number of cells scored, as well as the putative benefits of
      transforming the primary end points to common units by the use of reference
      standards and calibration curves. Eight experienced investigators scored pre-made
      slides of nuclei differently, but each investigator scored constantly over time.
      Scoring of 200 nuclei per treatment was associated with the lowest residual
      variation. Alkaline unwinding for 20 or 40 min and electrophoresis for 20 or 30
      min yielded different dose-response relationships of cells exposed to gamma
      radiation and it was possible to reduce the variation in oxidized purines in
      MNBCs from humans by adjusting the level of lesions with protocol-specific
      calibration curves. However, there was a difference in the level of DNA damage
      measured by different investigators and this variation could not be reduced by
      use of investigator-specific calibration curves. The mean numbers of lesions per
      10(6) bp in MNBCs from seven humans were 0.23 [95% confidence interval (CI): 0.14
      0.33] and 0.31 (95% CI: 0.20-0.55) for strand breaks (SBs) and oxidized guanines,
      respectively. In conclusion, our results indicate that inter-investigator
      difference in scoring is a strong determinant of DNA damage levels measured by
      the comet assay.

PMID- 18326869
TI  - Filter quality of pleated filter cartridges.
AB  - The performance of dust cartridge filters commonly used in dust masks and in room
      ventilation depends both on the collection efficiency of the filter material and
      the pressure drop across the filter. Currently, the optimization of filter design
      is based only on minimizing the pressure drop at a set velocity chosen by the
      manufacturer. The collection efficiency, an equally important factor, is rarely
      considered in the optimization process. In this work, a filter quality factor,
      which combines the collection efficiency and the pressure drop, is used as the
      optimization criterion for filter evaluation. Most respirator manufacturers pleat
      the filter to various extents to increase the filtration area in the limit space
      within the dust cartridge. Six sizes of filter holders were fabricated to hold
      just one pleat of filter, simulating six different pleat counts, ranging from 0.5
      to 3.33 pleats cm(-1). The possible electrostatic charges on the filter were
      removed by dipping in isopropyl alcohol, and the air velocity is fixed at 100 cm
      s(-1). Liquid dicotylphthalate particles generated by a constant output atomizer
      were used as challenge aerosols to minimize particle loading effects. A scanning
      mobility particle sizer was used to measure the challenge aerosol number
      concentrations and size distributions upstream and downstream of the pleated
      filter. The pressure drop across the filter was monitored by using a calibrated
      pressure transducer. The results showed that the performance of pleated filters
      depend not only on the size of the particle but also on the pleat count of the
      pleated filter. Based on filter quality factor, the optimal pleat count (OPC) is
      always higher than that based on pressure drop by about 0.3-0.5 pleats cm(-1).
      For example, the OPC is 2.15 pleats cm(-1) from the standpoint of pressure drop,
      but for the highest filter quality factor, the pleated filter needed to have a
      pleat count of 2.65 pleats cm(-1) at particle diameter of 122 nm. From the aspect
      of filter quality factor, this study suggests that the respirator manufacturers
      should add approximately 0.5 pleats cm(-1) to the OPC derived from the
      generalized correlation curve for pleated filter design based on minimum pressure
      drop.

PMID- 18326870
TI  - Respiratory performance offered by N95 respirators and surgical masks: human
      subject evaluation with NaCl aerosol representing bacterial and viral particle
      size range.
AB  - OBJECTIVES: This study aimed at determining the protection factors (PFs) provided
      by N95 filtering facepiece respirators and surgical masks against particles
      representing bacterial and viral size ranges (aerodynamic size: 0.04-1.3 mum).
      METHODS: The protection levels of N95 filtering facepiece respirators (four
      models) and surgical masks (three models) were investigated while they were
      donned by 12 subjects performing the OSHA (US Occupational Safety and Health
      Administration) fit-testing exercises in a test chamber. RESULTS: About 29% of
      N95 respirators and approximately 100% of surgical masks had PFs <10, which is
      the assigned PF designated for this type of respirator by the OSHA. On average,
      the PFs of N95 respirators were 8-12 times greater than those of surgical masks.
      The minimum PFs were observed in the size range of 0.04-0.2 mum. No significant
      difference in PF results was found between N95 respirators with and without an
      exhalation valve. CONCLUSIONS: The study indicates that N95 filtering facepiece
      respirators may not achieve the expected protection level against bacteria and
      viruses. An exhalation valve on the N95 respirator does not affect the
      respiratory protection; it appears to be an appropriate alternative to reduce the
      breathing resistance.

PMID- 18326871
TI  - Sampling of high amounts of bioaerosols using a high-volume electrostatic field
      sampler.
AB  - For studies of the biological effects of bioaerosols, large samples are
      necessary. To be able to sample enough material and to cover the variations in
      aerosol content during and between working days, a long sampling time is
      necessary. Recently, a high-volume transportable electrostatic field sampler for
      collection of fine particles has been described. The aim of this study was to
      investigate whether this sampler can be used for collection of high amounts of
      authentic bioaerosols that can subsequently be used for biological analysis. The
      investigation was carried out at a biofuel plant in a straw storage room and in a
      boiler room over two seasons. The sampled dust was quantified in terms of mass
      and characterized regarding microbial components and compared with dust sampled
      by Gravikon and GSP samplers. For the electrostatic field sampler, a prefilter
      was used to remove large objects. The prefilter was characterized for particle
      penetration and this testing indicated that the prefilter did not remove
      particles up to 10 mum, and therefore respirable dust was sampled by the
      electrostatic field sampler. Using the electrostatic field sampler in the straw
      storage and in the boiler room, 330 and 315 mg dust (net recovery of the
      lyophilized dust) was sampled during a period of 7 days, respectively. The
      sampling rates of the electrostatic field samplers were between 1.34 and 1.96 mg
      dust per hour, the value for the Gravikon was between 0.083 and 0.108 mg dust per
      hour and the values for the GSP samplers were between 0.0031 and 0.032 mg dust
      per hour. The standard deviations of replica samplings and the following
      microbial analysis using the electrostatic field sampler and GSP samplers were at
      the same levels. The exposure to dust in the straw storage was 7.7 mg m(-3) when
      measured by the electrostatic field sampler and 11.8 mg m(-3) when measured by
      the GSP inhalable dust sampler. The quantity (amount per mg dust) of total fungi,
      Aspergillus fumigatus, total bacteria, endotoxin and mesophilic actinomycetes
      sampled by the electrostatic field samplers and the Gravikon samplers varied
      within the same season by a factor smaller than four. The quantities of some
      microbial components were higher in the dust collected with all samplers in March
      than in August. In conclusion, by using the electrostatic field sampler, it was
      possible to sample replicas of large authentic aerosol samples that can be used,
      e.g. biological analysis.

PMID- 18326872
TI  - Buccal swabs and treated cards: methodological considerations for molecular
      epidemiologic studies examining pediatric populations.
AB  - Self-collection of buccal cells provides a noninvasive method for obtaining
      biologic samples for genetic analyses in pediatric studies. Nevertheless, low
      yields, microbial contamination, and degradation of buccal samples present
      challenges for epidemiologic studies incorporating genetic investigations. The
      aims of this study were to compare the quality and yield of DNA extracted from
      buccal specimens with BuccalAmp swabs (Epicenter BioTechnologies, Madison,
      Wisconsin) or FTA cards (Whatman, Inc., Clifton, New Jersey) and to investigate
      the use of whole-genome amplification (WGA) for increasing DNA yields for single
      nucleotide polymorphism analyses. Buccal specimens were collected from 55
      children with acute lymphoblastic leukemia and 52 control children without acute
      lymphoblastic leukemia in New South Wales, Australia, in 2003-2004. Real-time
      polymerase chain reaction was used to evaluate polymorphisms in the genes
      encoding the cytochrome p450 enzyme CYP3A4 (CYP3A4 A392G, also known as
      CYP3A4*1B) and the steroid xenobiotic receptor (SXR C25385T). Results showed that
      DNA could be isolated from buccal specimens collected by use of both methods and
      that yields could be substantially improved with WGA without introducing
      genotyping error. However, DNA quality was poorer in samples collected by
      BuccalAmp swabs, and the presence of polymerase chain reaction inhibitors in
      these samples reduced the sensitivity of quantitative real-time PCR analysis.
      These findings show that different methods for collecting buccal samples impact
      on the downstream success of genetic investigations and influence DNA quality
      after WGA.

PMID- 18326873
TI  - Diet, urate, and Parkinson's disease risk in men.
AB  - The authors examined whether a diet that increases plasma urate level is also
      related to reduced risk of Parkinson's disease (PD). The study population
      comprised 47,406 men in the Health Professionals Follow-up Study. The potential
      effect of diet on plasma urate level was estimated by regressing plasma urate on
      intakes of selected foods and nutrients in a subsample of 1,387 men. Coefficients
      of this regression model were then used to calculate a dietary urate index for
      all cohort participants. Multivariate relative risks of PD were estimated by
      means of Cox proportional hazards models. After 14 years of follow-up (1986
      2000), the authors documented 248 incident cases of PD. A higher dietary urate
      index was associated with a lower risk of PD (top quintile vs. bottom: relative
      risk = 0.47, p-trend = 0.0008), after adjustment for age, smoking, caffeine
      intake, and other potential confounders. This association remained strong and
      significant after further adjustment for each component of the index individually
      (p-trend < 0.02 for each). These data support urate as a potentially protective
      factor in PD and suggest that dietary changes expected to increase plasma urate
      level may contribute to lower risk of PD. These potential benefits, however,
      should be weighed against expected adverse effects on risk of gout and other
      chronic diseases.

PMID- 18326874
TI  - Counterpoint: There is not capillary recruitment in active skeletal muscle during
      exercise.

PMID- 18326877
TI  - Last word on Point:Counterpoint: There is/is not capillary recruitment in active
      skeletal muscle during exercise.

PMID- 18326878
TI  - Last word on Point:Counterpoint: There is/is not capillary recruitment in active
      skeletal muscle during exercise.

PMID- 18326879
TI  - A further comment on Point:Counterpoint "Airway smooth muscle is/is not useful".

PMID- 18326880
TI  - Distribution and differential induction of CYP2E1 by ethanol and acetone in the
      mesocorticolimbic system of rat.
AB  - AIMS: The expression of cytochrome P4502E1 (CYP2E1) in the brain has been
      demonstrated in several regions, nevertheless there is a lack of specific studies
      on the constitutive expression and induction at the mesocorticolimbic system, the
      most relevant brain pathway in the context of drug addiction and alcoholism.
      Hence, we have performed a detailed study of the CYP2E1 expression and induction
      in three key areas of the mesocorticolimbic system of the rat brain: prefrontal
      cortex (PFC), nucleus accumbens (NAc), and ventral tegmental area (VTA). METHODS:
      Expression levels of CYP2E1 were analyzed by Western blot. The induction of the
      enzyme in the selected brain areas by chronic acetone (1% v/v acetone in drinking
      water for 11 days) and ethanol (3 g/kg by gavage for 7 days) was also assessed.
      RESULTS: (i) CYP2E1 was expressed in PFC, Nac, and VTA, with the order of
      magnitude of the levels being VTA approximately PFC > Nac, and approximately 3
      13% of it was encountered in liver; (ii) acetone treatment significantly
      increased CYP2E1 expression in Nac, up to 212% of the control levels, whereas not
      significant changes were observed in VTA and PFC; (iii) chronic ethanol treatment
      only resulted in a significant induction of enzyme levels in VTA (124%). A
      similar enhancement, though not significant, was found to occur in NAc.
      CONCLUSIONS: CYP2E1 was present in the mesocorticolimbic system at different
      levels of expression. Chronic acetone and ethanol treatments are able to increase
      enzyme levels in specific areas of this system with the pattern of induction of
      the two agents being different.

PMID- 18326881
TI  - Successful pre-transplant management of a patient with anti-factor H
      autoantibodies-associated haemolytic uraemic syndrome.

PMID- 18326882
TI  - New-onset diabetes after transplantation--should it be a factor in choosing an
      immunosuppressant regimen for kidney transplant recipients.

PMID- 18326883
TI  - A non-invasive, on-line deuterium dilution technique for the measurement of total
      body water in haemodialysis patients.
AB  - BACKGROUND: Despite its importance, total body water (TBW) is usually estimated
      rather than measured due to the complexity of isotope dilution methods. The aim
      of this study was to demonstrate the applicability in haemodialysis (HD) patients
      of a recently developed on-line breath test, previously validated in healthy
      subjects, that uses the gold standard deuterium dilution method to measure TBW.
      In particular we wished to show that a pre-dialysis estimation was as good as a
      post-dialysis equilibrated measurement in order to avoid patients needing to
      remain behind after dialysis treatment. METHODS: The dispersal kinetics of breath
      HDO, measured using a flowing afterglow mass spectrometer (FA-MS) following
      ingestion of D(2)O immediately post-dialysis, were determined in 12 haemodialysis
      patients and used to calculate the absolute TBW(PostHD) after full equilibration.
      TBW(PreHD) was then determined from breath samples taken immediately prior to the
      next dialysis. This measurement was adjusted for the interdialytic weight change
      and urine output (TBW(PreHD-adjusted)) and compared to the TBW(PostHD). The
      accuracy and precision of FA-MS was also assessed using known concentrations of
      deuterium-enriched water samples. RESULTS: Mean TBW(PostHD) was 50.0 +/- 9.3 L
      and TBW(PreHD-adjusted) was 50.7 +/- 9.0 L. They were highly correlated (R =
      0.99, P < 0.001) with a CV of 2.6%. The mean difference was +0.74 L (SEM 0.35,
      95% CI -0.03 to 1.51 L, P = 0.059), compatible with a daily insensible loss of
      0.37 L. Accuracy and precision of FA-MS were comparable to the previous
      validation work. CONCLUSIONS: This non-invasive adaptation of the D isotope
      dilution method for determining TBW can be applied to haemodialysis patients who
      show deuterium equilibration kinetics identical to normal subjects; a pre
      dialysis estimation may be used to determine TBW, and so avoiding the necessity
      to remain behind after dialysis making this suitable for application in the
      clinical setting.

PMID- 18326884
TI  - Tissue inhibitor of metalloproteinase-1 exacerbated renal interstitial fibrosis
      through enhancing inflammation.
AB  - BACKGROUND: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is associated with
      renal fibrosis. Furthermore, it is a multi-functional protein, and whether it has
      other roles in renal fibrosis is unknown. As several inflammatory mediators are
      substrates of matrix metalloproteinases (MMPs), TIMP-1 might affect renal
      fibrosis via inflamatory pathways. METHODS: Plasmids containing the sense and
      antisense human TIMP-1 sequence were stably transfected into the human kidney
      proximal tubular epithelial cell line (HKC), MMP-2 and MMP-9 siRNA were
      transiently transfected into HKC and the transfected cells were stimulated with
      phorbol 12-myristate 13-acetate (PMA). In vivo, we established unilateral
      ureteral obstruction (UUO) models by using homozygote human TIMP-1 transgenic
      mice. The expression of intercellular adhesion molecule-1 (ICAM-1) in transfected
      cells and F4/80-positive cells in the renal interstitium were examined by
      indirect immunofluorescence. Protein levels in the cells and UUO models were
      examined by western blot, and the activities of the gelatinases and TIMP-1 were
      examined by gelatin zymography and reverse zymography, respectively. RESULTS:
      After stimulation with PMA, the activities of the gelatinases were decreased,
      ICAM-1 was upregulated, and soluble ICAM-1 in the supernatant was decreased, in
      HKC transfected with sense TIMP-1, and ICAM-1 was increased in HKC transfected
      with MMP-9 siRNA. At 14 days after UUO, it was found that compared with wild-type
      mice, in transgenic mice, with upregulation of TIMP-1, activities of gelatinases
      were downregulated, ICAM-1, transforming growth factor-beta1 (TGF-beta1),
      collagens I and III were upregulated, and the extent of renal fibrosis and
      infiltration of macrophages was more severe. CONCLUSION: Overexpression of TIMP-1
      could promote renal interstitial fibrosis through the inflammatory pathway, which
      might be partly induced by upregulating ICAM-1.

PMID- 18326885
TI  - Acceptance testing and routine quality control in general radiography: mobile
      units and film/screen fixed systems.
AB  - This study presents the findings from acceptance testing and routine quality
      control (QC) of general radiographic X-ray equipment in Ireland during 2006 and
      early 2007, including mobile X-ray units and film/screen fixed systems.
      Acceptance testing and routine QC of the diagnostic X-ray imaging equipment are
      requirements of European and Irish legislation. One hundred general radiographic
      X-ray systems were tested within Ireland, 73% of them failed to meet the required
      QC guidelines, whereby one or more faults were identified. The majority of these
      failures were minor ones, requiring attention by the suppliers at the next
      routine service. Significant faults were only identified in seven systems. The
      suppliers were requested to investigate these issues as soon as possible and take
      the necessary corrective action. A review of the QC results highlights the need
      to perform comprehensive acceptance and routine testing of the systems.

PMID- 18326886
TI  - Patient skin dose assessment during CT-guided interventional procedures.
AB  - The purpose of this study was to investigate patient skin doses in the most
      frequent computed tomography-guided interventional radiology procedures. The
      study includes 14 abdominal biopsies and 15 radiofrequency (RF) ablations.
      Patient skin dose was assessed by slow verification films. The technical factors
      recorded were: tube kilovoltage (kVp), tube load (mAs), slice thickness and the
      total number of slices (S). The median value of maximum entrance skin dose
      (ESD(M)) in biopsy was 108 mGy (9.5-282 mGy). S had a range of 4-152 with a
      median of 44 slices. Significant correlation was found between S and dose (r =
      0.80). Median ESD(M) in RF ablation was 238 mGy (104-500 mGy). S had a range of
      108-175 with a median of 155 slices. No significant correlation was found between
      S and dose. The large range of results show that a more extensive investigation
      should be performed. In summary, diagnostic procedures such as biopsy present
      patient skin doses that are relatively low. On the other hand, patient skin dose
      in RF ablation can be high and can reach values higher than the value that a slow
      verification film is capable of measuring (1.2 Gy). For these procedures, an
      alternative method should be investigated.

PMID- 18326887
TI  - From Ubombo to Mkhuzi: disease, colonial science, and the control of Nagana
      (livestock trypanosomosis) in Zululand, South Africa, C. 1894-1953.
AB  - This article looks at the scientific studies and debates that surrounded the
      control of nagana (trypanosomosis in livestock) in Zululand, South Africa, from
      the late nineteenth century until the 1950s. By 1953 the disease appeared to be
      contained following the use of DDT to exterminate the tsetse fly that spread the
      infection from immune wildlife to susceptible livestock. It argues that South
      Africa made an important contribution to western knowledge about trypanosomosis
      in terms of its etiology and possibilities for its control-a fact that has often
      been overlooked in the historical literature that has tended to focus on events
      in colonial central and east Africa. It explores Zulu conceptualizations of
      nagana, which influenced early researchers, the evolution of veterinary,
      entomological, and ecological sciences as "tools" for understanding and
      suppressing disease, as well as the difficulties involved in reconciling game
      conservation with colonial settlement. The article also shows how an animal
      disease contributed to the development of colonial science and encouraged the
      expansion of scientific networks with African colonies and beyond.

PMID- 18326888
TI  - Augmenting clinical evaluation of hemiparetic arm movement with a laboratory
      based quantitative measurement of kinematics as a function of limb loading.
AB  - BACKGROUND: Kinematic and kinetic measurements used in laboratory settings can
      quantify upper extremity movement impairment following stroke, but their
      relationship to clinical methods of evaluating movement impairment is unclear.
      OBJECTIVE: To test whether the Arm Coordination Training 3D device (ACT3D) could
      provide a repeatable quantitative measurement of range of motion during upper
      extremity reaching along a range of functional levels of loads on the arm and
      correlate with clinical assessments of arm impairment. METHODS: Work area during
      reaching along clockwise and counterclockwise hand paths was measured under 9
      limb-loading conditions ranging from no load to twice the weight of the upper
      extremity in 11 individuals with chronic hemiparetic stroke on 2 separate
      occasions. Participants were given a battery of clinical assessments that
      included the Fugl-Meyer Motor Assessment, Chedoke McMaster Stroke Assessment,
      Reaching Performance Scale, Modified Ashworth Scale, and the Stroke Impact Scale,
      by a physical therapist who did not know the results of the kinematic studies.
      RESULTS: A reproducible test-retest reduction in work area was found when
      participants were required to support up to and beyond the weight of their limb.
      Work area was correlated with most upper extremity clinical assessments,
      suggesting criterion validity. CONCLUSIONS: Reaching work area during various
      loading conditions is a robust measurement that quantifies the effect of abnormal
      joint torque coupling and provides useful data that can be applied in the
      clinical setting.

PMID- 18326889
TI  - Endurance and resistance exercise training programs elicit specific effects on
      sciatic nerve regeneration after experimental traumatic lesion in rats.
AB  - OBJECTIVE: To evaluate the effects of endurance, resistance, and a combination of
      both types of exercise training on hindlimb motor function recovery and nerve
      regeneration after experimental sciatic nerve lesion in rats. METHODS: Sciatic
      nerve crush was performed on adult male rats, and after 2 weeks of the nerve
      lesion, the animals were submitted to endurance, resistance, and a combination of
      endurance-resistance training programs for 5 weeks. Over the training period,
      functional recovery was monitored weekly using the Sciatic Functional Index (SFI)
      and histological and morphometric nerve analyses were used to assess the nerve
      regeneration at the end of the trainings. RESULTS: The SFI values of the
      endurance-trained group reached the control values from the first posttraining
      week and were significantly better than both the resistance-trained group at the
      first, second, and third posttraining weeks and the concurrent training group at
      the first posttraining week. At the distal portion of the regenerating sciatic
      nerve, the endurance-trained group showed a greater degree of the myelinated
      fiber maturation than the sedentary, resistance-trained, and concurrent training
      groups. Furthermore, the endurance-trained group showed a smaller percentage area
      of endoneurial connective tissue and a greater percentage area of myelinated
      fibers than the sedentary group. CONCLUSION: These data provide evidence that
      endurance training improves sciatic nerve regeneration after an experimental
      traumatic injury and that resistance training or the combination of 2 strategies
      may delay functional recovery and do not alter sciatic nerve fiber regeneration.

PMID- 18326890
TI  - Motor cortical disinhibition during early and late recovery after stroke.
AB  - BACKGROUND: Functional neuroimaging studies show adaptive changes in areas
      adjacent and distant from the stroke. This longitudinal study assessed whether
      changes in cortical excitability in affected and unaffected motor areas after
      acute stroke correlates with functional and motor recovery. METHODS: We studied
      13 patients with moderate to severe hemiparesis 5 to 7 days (T1), 30 days (T2),
      and 90 days (T3) after acute unilateral stroke, as well as 10 healthy controls.
      We used paired-pulse transcranial magnetic stimulation to study intracortical
      inhibition and facilitation, recording from the bilateral thenar eminences. F
      waves were also recorded. RESULTS: At T1, all patients showed significantly
      reduced intracortical inhibition in the unaffected hemisphere. At T2, in patients
      whose motor function recovered, intracortical inhibition in the unaffected
      hemisphere returned to normal. In patients with poor clinical motor recovery,
      abnormal disinhibition persisted in both hemispheres. At T3, in patients whose
      motor function progressively recovered, the abnormal disinhibition in the
      unaffected hemisphere decreased further, whereas in patients whose motor function
      remained poor, abnormal inhibition in the unaffected hemisphere persisted. No
      modification of F-wave latency and amplitude were found in patients and controls.
      CONCLUSIONS: During early days after stroke, motor cortical disinhibition
      involves both cerebral hemispheres. Longitudinal changes in motor disinhibition
      of the unaffected hemisphere may reflect the degree of clinical motor recovery.

PMID- 18326891
TI  - Determining the optimal challenge point for motor skill learning in adults with
      moderately severe Parkinson's disease.
AB  - OBJECTIVE: To test the predictions of the Challenge Point Framework (CPF) for
      motor learning in individuals with Parkinson's disease (PD) by manipulating
      nominal task difficulty and conditions of practice. METHODS: Twenty adults with
      PD and 20 nondisabled controls practiced 3 variations of a laboratory-based goal
      directed arm movement over 2 days. A between-group (PD, nondisabled) 2-factor
      design compared 2 levels of nominal task difficulty (low, high) and 2 levels of
      practice condition (low, high demand). Learning was assessed with a no-feedback
      recall test 1 day after practice. Performance was quantified using a root mean
      square error difference between the goal and participant-generated movement.
      RESULTS: All participants improved with practice. Under the low-demand practice
      condition, adults with PD demonstrated comparable learning to that of controls
      when nominal task difficulty was low but not high. In contrast, under the high
      demand practice condition, adults with PD demonstrated preserved motor learning
      for both levels of task difficulty, but only if recall was tested under the same
      context as that used during practice. CONCLUSIONS: In general, the predictions of
      CPF were supported. Together, the level of nominal task difficulty and the
      inherent demand of the practice condition played a critical role in determining
      the optimal challenge point for motor learning in individuals with PD. More
      important, and in contrast to the predictions of CPF, a high-demand practice
      condition appeared to have a facilitative effect on motor learning. However, this
      benefit revealed the context specificity of motor learning in adults with PD.

PMID- 18326892
TI  - Nuclear sphingolipids: metabolism and signaling.
AB  - Sphingolipids are most prominently expressed in the plasma membrane, but recent
      studies have pointed to important signaling and regulatory roles in the nucleus.
      The most abundant nuclear sphingolipid is sphingomyelin (SM), which occurs in the
      nuclear envelope (NE) as well as intranuclear sites. The major metabolic product
      of SM is ceramide, which is generated by nuclear sphingomyelinase and triggers
      apoptosis and other metabolic changes. Ceramide is further hydrolyzed to free
      fatty acid and sphingosine, the latter undergoing conversion to sphingosine
      phosphate by action of a specific nuclear kinase. Gangliosides are another type
      of sphingolipid found in the nucleus, members of the a-series of gangliotetraose
      gangliosides (GM1, GD1a) occurring in the NE and endonuclear compartments. GM1 in
      the inner membrane of the NE is tightly associated with a Na(+)/Ca(2+) exchanger
      whose activity it potentiates, thereby contributing to regulation of Ca(2+)
      homeostasis in the nucleus. This was shown to exert a cytoprotective role as
      absence or inactivation of this nuclear complex rendered cells vulnerable to
      apoptosis. This was demonstrated in the greatly enhanced kainite-induced seizure
      activity in knockout mice lacking gangliotetraose gangliosides. The pathology
      included apoptotic destruction of neurons in the CA3 region of the hippocampus.
      Ca(2+) homeostasis was restored in these animals with LIGA-20, a membrane
      permeant derivative of GM1 that entered the NE and activated the nuclear
      Na(+)/Ca(2+) exchanger. Some evidence suggests the presence of uncharged
      glycosphingolipids in the nucleus.

PMID- 18326893
TI  - Pattern of germ cell testicular carcinoma in Dharmais Cancer Hospital between
      January 2000-December 2004.
AB  - AIM: to find out the distribution of germ cell tumor based on age,
      histopathology, stadium, chemotherapy regimen, and number of cases per year in
      patients hospitalized in Dharmais National Cancer Hospital during the period of
      January 2000 to December 2004. METHODS: the data were collected from medical
      record of patients with testicular carcinoma that were treated on inpatient and
      outpatient basis in Dharmais National Cancer Hospital during the period of
      January 2000 to December 2004. The data were collected, recorded and analyzed in
      descriptive manner and presented in tables of distribution and frequency.
      RESULTS: there were 44 cases testicular carcinoma being analyzed; 40 cases
      (90.92%) were germ cell tumor, 42.50% aged 21-30 years old; and the most frequent
      histological type was seminoma (47.50%). About 39.50% of the patients were
      admitted in stage II of the disease, and 61.59% were put on BEP regimen. Seminoma
      type was more frequent in >or= 30-year-old age group while on the other hand, non
      seminoma was mostly found in <or= 30-year-old patients. There was a relative
      increase of germ cell tumor cases from January 2000 to December 2004 in Dharmais
      National Cancer Hospital. CONCLUSION: germ cell tumors were the most common
      testicular carcinoma in Dharmais National Cancer Hospital from January 2000 to
      December 2004. Most of the patients were of 21-30-year-old age group. Seminoma
      type, particularly germ cell tumor, was more frequent than non-seminoma. Most of
      the patients were admitted to the hospital in the stage II of the disease and the
      most common chemotherapy used were BEP regiment. There was an increased number of
      germ cell tumor cases from January 2000 to December 2004 in Dharmais National
      Cancer hospital.

PMID- 18326894
TI  - Serum complement 3 (C3) and complement 4 (C4) level in febrile neutropenia
      patients at Dr. Kariadi Hospital, Semarang and Dr. Moewardi Hospital, Surakarta.
AB  - AIM: to identify the serum complement 3 (C3) and complement 4 (C4) level in
      febrile neutropenia and non-febrile neutropenia patients. METHODS: this is a
      cross-sectional prospective study. Samples were collected from patients with
      febrile neutropenia as sample group and patients with neutropenia but without
      fever as control. Both groups were tested for serum complement 3 and complement 4
      level, and the data were analyzed using student T-test. RESULTS: from 37
      neutropenia patients, 23 were classified as febrile neutropenia group and 14 in
      non-febrile neutropenia as control group. Total mean neutrophil count was
      653.22/ml serum in sample group and 594.36/ml serum in control group (p=0.575).
      Mean C3 level was 95.74 ug/dl in sample group and 130.00 ug/dl in control group,
      showing significant difference with p=0.031. The mean serum C4 level was 34.13
      ug/ml in sample group and 34.00 ug/dl in control group, the difference is not
      significant with p=0.98. When sample C3 and C4 data were combined, the total
      level was 125.61 ug/ml, which was significantly lower than the total C3 and C4 in
      control group 184.07 ug/dl. (p=0.04). CONCLUSION: in febrile neutropenia there is
      significant decrease of serum C3 level compared to non-febrile neutropenia. Serum
      C4 level in febrile neutropenia group is lower than the non-febrile neutropenia
      group, but the difference is not significant.

PMID- 18326895
TI  - Comparison of pro B-natriuretic peptide in hypertensive patients with and without
      diastolic dysfunction.
AB  - AIM: to evaluate whether pro BNP can be used for detection of diastolic
      dysfunction. METHODS: thirty nine hypertensive patients with normal systolic
      function, consecutively referred for echocardiography examination between October
      and December 2004 were recruited in the study. Diastolic dysfunction was
      diagnosed when echocardiographic mitral flow pattern demonstrated impaired
      relaxation, pseudonormalization or restrictive like patterns. NT-pro BNP levels
      were assessed using electro chemiluminescence Immunoassay (ECLIA) method.
      Unpaired t test was used to analyze the results. RESULTS: twelve out of thirty
      nine subjects had normal diastolic function. All base line characteristics,
      except for uric acid, were equally distributed between normal and abnormal
      diastolic function group. NT-pro BNP levels were nearly significantly higher in
      the diastolic dysfunction group (P=0.053). CONCLUSION: NT-pro BNP levels trends
      to be higher in hypertensive subjects with diastolic dysfunction.

PMID- 18326896
TI  - Conventional radiology and right heart catheterization in estimating primary
      pulmonary hypertension and pulmonary hypertension secondary to left-sided
      valvular disease.
AB  - AIM: to estimate the comparative value of conventional radiology and cardiac
      catheterization in establishing the diagnosis and severity of primary and
      secondary pulmonary hypertension. We also tried to achieve some correlations
      between the radiological and invasive parameters. METHODS: we performed a
      retrospective study over an 11-years time period, analyzing data from a group of
      14 patients diagnosed with primary pulmonary hypertension compared to a matched
      group of 20 patients suffering from pulmonary hypertension secondary to mitral
      and aortic valvular disease. All the patients had undergone conventional
      radiology (chest X-ray) and catheterization of the right heart cavities and
      pulmonary artery. RESULTS: we detected significantly elevated pulmonary artery
      pressures and resistances in the primary pulmonary hypertension group compared to
      secondary hypertension patients. Cardiac output values were much lower in the
      primary pulmonary hypertension individuals compared with secondary pulmonary
      hypertension in left-sided valvular disease. The pulmonary artery arch diameter,
      the diameter of the right descending pulmonary artery and the value of the
      arterio-bronchial ratio were similar in the two groups. CONCLUSION: in both
      groups, we found a statistically significant positive correlation between the
      values of the pulmonary artery vascular resistance and the diameter of the right
      descending pulmonary artery, which are very specific parameters in the diagnosis
      of pulmonary hypertension. In the primary pulmonary hypertension group we
      identified a significant inverse correlation between the diameter of the right
      descending pulmonary artery and the values of cardiac output. This finding was
      not confirmed in the secondary group.

PMID- 18326897
TI  - Neutropenic enterocolitis in breast cancer patient after taxane-containing
      chemotherapy.
AB  - Neutropenic enterocolitis or typhlitis (from the Greek typhlon, meaning caecum)
      is defined as a necrotizing colitis with inflammation of the cecum and
      surrounding tissues. Although this condition occurs primarily in severely
      myelosuppressed and immunosuppressed patients with leukemia, it may also occur in
      those with other advanced malignancies receiving myelosuppressive chemotherapy.
      It has been described most recently in patients with solid tumors who receive
      taxane-based therapy. A 60-year old woman with medullary breast cancer stage IIIB
      underwent neoadjuvant chemotherapy with TAC (doxetaxele 100 mg/m2, doxorubicin 50
      mg/m2 and cyclophosphamide 600 mg/m2). Sixth day after TAC chemotherapy, she had
      abdominal pain and vomiting. Abdomen CT scan showed diffuse circumferential
      thickening of ileum wall typical for ileitis, narrowing of the lumen, disturbance
      of peristaltic. This abdomen CT scan was thought as abnormality pictures of
      neutropenic enterocolitis. Neutropenic enterocolitis should be considered in
      patients with abdominal symptoms especially during the granulocyte nadir
      following chemotherapy. Increased awareness of this rapidly progressive and
      potentially fatal disease leads to accurate diagnosis and the prompt treatment
      that can decrease morbidity and mortality.

PMID- 18326898
TI  - DVT in tonsil sarcoma.

PMID- 18326899
TI  - Oral anticoagulant treatment in management of elderly patients with atrial
      fibrillation [corrected]: is it beneficial or detrimental?
AB  - Atrial fibrillation (AF) is supraventricular tachyarrhythmia characterized by
      uncontrolled atrial activation, and deteriorates atrial function. In AF patients,
      increasing of age is related with enlarge left atrium (LA), diminished flow
      velocity of left atrial appendage (LAA), and spontaneously contrast echo, with
      other factors which are predisposition for LA thrombus. In AF patients,
      thromboemboli after cardioversion without anticoagulant administration is 1.5
      3.0%. Elderly patient is not contraindication for anticoagulant, although higher
      risk for bleeding. For stroke prevention in >65 years of age whilst the patient
      is candidate for oral anticoagulant warfarin, it should be prescribed to reach
      INR 2.0-3.0. Some reports on anticoagulant evaluation (INR) and bleeding as
      complication of warfarin prescribed for AF treatment are not significantly
      different in elderly and younger patients.

PMID- 18326900
TI  - Acute respiratory distress syndrome.
AB  - Acute respiratory distress syndrome (ARDS) is a syndrome of injured lung due to
      any systemic inflammatory responses. The decline in ARDS mortality mostly
      attributed to improvements in standard supportive care. There are still no data
      from any large multicenter randomized clinical trial ever demonstrated to reduce
      mortality other than the recommended by the National Institutes of Health (NIH)
      ARDS Network published in 2000.

PMID- 18326901
TI  - [Effect of ghrelin on duodenal myoelectric activity in conscious rats].
AB  - OBJECTIVE: To explore the effect of ghrelin on the duodenal myoelectrical
      activity during the feeding state and the fasting state in rats. METHODS: One
      pair of bipolar silver electrodes were chronically implanted in the duodenal
      serosa of rats for electromyography. The myoelectrical activity was recorded when
      ghrelin was injected intravenously into rats during the feeding state or the
      fasting state. Some rats were pretreated with atropine, phentolamine,
      propranolol, L-arginine, and (D-Lys3)GHRP-6 respectively to explore the mechanism
      of ghrelin. RESULTS: Duodenal migrating myoelectrical complex (MMC) could be
      induced by ghrelin in the feeding state. Ghrelin could shorten the length of
      duodenal MMC cycle and increase the amplitude and frequency of phase III during
      the fasting state. The percentage of phase III in the MMC cycle did not change.
      These effects were inhibited by atropine and L-arginine (D-Lys3)GHRP-6, but not
      by propranolol and phentolamine. CONCLUSION: Ghrelin seems to be closely related
      to the duodenal motility. The excitatory effect of ghrelin on duodenal MMC might
      rely on the cholinergic pathway, and have a close relationship with NO. The
      receptor of ghrelin can regulate its activity.

PMID- 18326902
TI  - [Neurons in the corpus callosum of rats: expression of Cav2.2 and their
      connection].
AB  - OBJECTIVE: To prove the existence neurons in the rat corpus callosum, the
      potential function of these neurons and their connection. METHODS:
      Immunohistochemistry was used performed to examine the expressions of NeuN, a
      mature neuron marker,and N-type voltage-dependent valcium channel alpha1-subunit
      (Cav2.2)in the section of the rat corpus callosum. Horseradish peroxidase (HRP)
      normal sodium solution (30%), the retrograde tracer,was injected under the
      frontal forceps of corpus callousm and HRP absorbed by the process of neurons in
      the brain slices was stained with tetramethyl benzidine. RESULTS: There were some
      NeuN positive cells in the rat corpus callosum and Cav2.2 was detected in some of
      these NeuN positive cells.Neurons with positive HRP were found in the rat corpus
      callosum and some of these neurons connected to the cortex or corpus striatum.
      CONCLUSION: There are a few neurons in the corpus callosum of adult rats and some
      of them express Cav2.2. Neurons in the corpus callosum have connections with the
      brain cortex or corpora striatum.

PMID- 18326903
TI  - [Effect of overexpression of glycosylphosphatidylinositol-specific phospholipase
      D on biological character of hepatocellular carcinoma cell line HepG2].
AB  - OBJECTIVE: To investigate the effect of overexpression of glycosylphosphatidyl
      inositol-specific phospholipase D (GPI-PLD) on the biological character of
      hepatocellular carcinoma cell line HepG2. METHODS: The GPI-PLD gene eukaryon
      expression vector pcDNA3.1(+)/ GPI-PLD was transiently transfected into HepG2
      cell by lipid-media transfection. The untransfected HepG2 and HepG2 transfected
      with pcDNA3.1(+) were used as controls. After screening with G418, the single
      clone was obtained. The expression level of GPI-PLD mRNA in HepG2 was identified
      by reverse transcription polymerase chain reaction (RT-PCR). GPI-PLD activities
      were analyzed quantitatively by triton-X-114 partition with GPI anchored
      placental alkaline phosphatase (PLAP) as a substrate. Cell count was used to
      detect the proliferation of the 3 groups, and complement dependent cytotoxicity
      (CDC) effects were observed by the staining of trypan blue. Apoptosis cells were
      analyzed by flow cytometry. Carcinoembryonic antigen (CEA)was detected by enzyme
      linked immunosorbent assay (ELISA). RESULTS: Compared with HepG2 and
      pcDNA3.1(+)/HepG2 cell, the levels of GPI-PLD activities and its mRNA from
      pcDNA3.1(+)/GPI-PLD/HepG2 were increased with almost 2 to 5 times,respectively.
      The GPI anchored PLAP and CEA released into the medium by GPI-PLD, and the rate
      of CDC killing on the cells were significantly increased. However, the
      proliferative capacity was obviously decreased, and the typical apoptosis cells
      were presented in positive clones and its apoptosis rates were increased
      significantly. CONCLUSION: The stable cell line with overexpression of GPI-PLD
      has been constructed. The overexpression of GPI-PLD in these cells increases the
      sensitivity of these cells to CDC killing and impairs the proliferative capacity
      of cells, and promotes the apoptosis.

PMID- 18326904
TI  - [Killing effect improved by fusion gene HRE1.Egr-1. yCDglyTK on gene-radio
      therapy of nasopharyngeal cancer in vitro].
AB  - OBJECTIVE: To construct hypoxia/radiation inducible promotor HRE1.Egr-1, and to
      observe its promotive effect on the expression of yCDglyTK gene in nasopharyngeal
      cancer HNE-1 cells and the anti-tumor effect of yCDglyTK and to lay an
      experimental foundation for further exploration of new gene-radio therapy of
      nasopharyngeal cancer. METHODS: pcDNA3.1(-)HRE1.Egr-1.yCDglyTK was constructed by
      gene recombination technique. Stable yCDglyTK-expressing HNE-1 cells were
      generated by transfecting the recombinant plasmid into the target cells with
      liposome. The expression of yCDglyTK was detected by Western blot in 4 groups: a
      normoxia group, a radiation group, a hypoxia group, and a hypoxia and radiation
      group. The killing effect of 5-FC in different circumstances was determined by
      MTT. RESULTS: The expression of yCDglyTK/5-FC gene in all the groups was
      significantly different(P<0.01),especially in the hypoxia and radiation group.
      The killing effect of 5-FC on HNE1 cells varied under different conditions,
      especially in the hypoxia and radiation group. CONCLUSION: Hypoxia and radiation
      can induce the activity of fusion promoter HRE1.Egr-1, and obviously promote the
      anti-tumor effect of yCDglyTK/5-FC system, suggesting that yCDglyTK may be a
      candidate suicide gene for gene-radio therapy of NPC.

PMID- 18326905
TI  - [Establishment and evaluation of a bone cancer pain model].
AB  - OBJECTIVE: To explore the feasibility of a bone cancer pain model by injecting
      the Lewis lung carcinoma cells into the femur bone marrow cavity of C57BL/6 mice.
      METHODS: Sixty clear grade male C57BL/6 mice (body weight 18 approximately 20 g)
      were randomly divided into 4 groups(15 in each group). Cancer cell inoculated
      group: 2*10(6) Lewis lung carcinoma cells in 10 microL PBS were injected into the
      left femur bone marrow cavity, and the other 3 control groups were injected the
      heat inactivated Lewis cells, PBS, or a false operation respectively. Spontaneous
      lifting time and mechanical allodynia threshold of the mice hind paw were
      measured in the alternative days throughout the experiment. The structural damage
      of the femur was monitored by radiogram on the 7th,15th, and 23rd day
      respectively,and the pathohistological changes of the femur bones were observed
      by HE staining on the same days. RESULTS: Those mice that received intra-femur
      innoculation of Lewis lung carcinoma cells gradually developed the spontaneous
      pain, which was began on the 11th day after the innoculation, and followed by
      mechanical allodynia. The course of flinch lasted in the later experimental
      session. The 50% Von Frey threshold was significantly decreased on the 13th day
      after the innoculation, and the mechanical allodynia lasted the whole
      experimental period. On the 23rd day after the innoculation, X-ray film showed
      that the medullary cavity of ipsilateral distal femur was filled with tumor
      cells, and the cortical bone became thick; furthermore, the tumor cells invaded
      the peripheral muscles. CONCLUSION: Injecting the Lewis lung carcinoma cells into
      the femoral medullary cavity of C57BL/6 mice can successfully establish a murine
      bone cancer pain model, and the murine model shows much resemblance compared with
      the human bone cancer pain.

PMID- 18326906
TI  - [Trophoblast cells invaing the placenta bed and change of spiral arteries and
      microvessels in pre-eclampsia].
AB  - OBJECTIVE: To investigate the invason of trophoblasts in the placenta bed and the
      change of spiral arteries and microvessels in pre-eclampsia and normal pregnancy.
      METHODS: Twenty cases of normal pregnancies, mild pre-eclampsia and severe pre
      eclampsia were chosen as Group A, Group B, and Group C. HE staining and
      immunohistochemistry staining (SP method) were used to observe the depth and the
      density of trophoblasts invading the placenta bed and the change of spiral
      arteries and microvessels. RESULTS: The significant difference in the degree of
      invasion was in the superficial myometrial segment. Group C was the most
      superficial in the 3 groups (P<0.01). The density of trophoblasts which invaded
      the placenta bed in the lower half of the basal decidual segment and the
      myometrial segment showed us Group C was the lowest (P<0.01). There was
      statistical difference among the 3 groups (P<0.01). The average lumen area of the
      spiral arteries in the decidual segment and the superficial myometrial segment of
      the placenta bed was the smallest in Group C among the 3 groups(P<0.01) and there
      was statistical difference among the 3 groups (P<0.01). The spiral arteries were
      the thickest in Group C with statistical difference among the 3 groups (P<0.01).
      The physiological and pathological change of the spiral arteries was mainly in
      the superficial myometrial segment. The incidence rate of physiological changes
      in the spiral arteries was the lowest in Group C with statistical difference
      among the 3 groups (P<0.01). The incidence rate of pathological changes was the
      highest in Group C (P<0.01) and the normal group was the highest. There was
      significant difference among the 3 groups(P<0.01). There was positive correlation
      between the physiological change of the spiral arteries and the invaing degree of
      the trophoblasts (P<0.05), there was negative correlation between the
      pathological change of the spiral arteries and the invasion depth as well as the
      invasion density of the trophoblasts(P<0.05). There was negative correlation
      between the physiological change and the pathogenetic condition of pre
      eclampsia(P<0.05)while there was positive correlation between the pathological
      change and the pathogenetic condition degree of pre-eclampsia(P<0.05). There was
      negative correlation between the invasion depth as well as density in uteruso
      superficial myometrial segment by trophoblast and the pathogenetic condition
      degree of pre-eclampsia(P<0.05). There was invasion trophoblast in 62.50% lumen
      wall of spiral arteries in uterus superficial myometrial segment of the placental
      bed in normal pregnancy while 27.5% was seen in severe pre-eclampsia.
      Microvascular density in the decidual segment and the superficial myometrial
      segment of the placenta bed in Group C was the lowest among the 3 groups with
      statistical difference (P<0.01). CONCLUSION: The invasion depth of the
      trophoblasts in pre-eclampsia was more superficial than normal pregnancy.The
      changes of the invasion of the trophoblasts and the pathological changes of the
      spiral arteries in the placenta bed mainly existed in the superficial myometrial
      segment which was closely related to the severity of the illness. That
      microvascular density in the placental bed of pre-eclampsia started to decrease
      from the basal decidual segment shows that the microvessel development in the
      placenta bed is impaired in pre-eclampsia.

PMID- 18326907
TI  - [Effect of carbon dioxide pneumoperitoneum-laparoscopic surgery on tumor seeding
      and metastases in endometrial cancer].
AB  - OBJECTIVE: To explore the influence of carbon dioxide pneumoperitoneum
      laparoscopic surgery on tumor cell seeding and metastases in endometrial cancer.
      METHODS: Twenty patients with endometrial cancer who underwent laparoscopic
      surgery and 10 patients with endometrial cancer who underwent laparotomic surgery
      were enrolled. Each patient was in preoperative clinical StageIand the uterus
      size in each patient was less than 12 weeks of pregnancy. Carbon dioxide
      pneumoperitoneum was established and maintained with CO2 insufflation at 4
      approximately 6 L/min and intraperitoneal pressure of 13 mmHg with an automatic
      pneumoperitoneum machine. Cytologic examination of peritoneal fluid(at the
      beginning and end of the operation), CO2 filtrated gas and the lavage fluid of
      instruments during the laparoscopic surgery were performed. The protein
      expressions of E-cadherin,beta-catenin,P-selectin,matrix metalloproteinase-2(MMP
      2),vascular endothelial growth factor (VEGF),and CD44v6 in tumor tissues before
      and after the operation were detected by DAKO Envision. RESULTS: There were no
      case of positive washing cytology in the peritoneal fluid,CO2 filtrated gas, and
      the lavage fluid of instruments during the laparoscopic surgery. The expressions
      of E-cadherin and beta-catenin proteins were obviously abnormal in endometrial
      cancer. The abnormal expressions of E-cadherin and beta-catenin protein between
      the pre- and post-operations were not significantly different in both the
      laparoscopic group and the laparotomic group(P>0.05).The changes of abnormal
      expressions of E-cadherin and beta-catenin protein were no statistical difference
      between the two groups(P>0.05). The positive protein expressions of P
      selectin,MMP-2,VEGF,and CD44v6 were not significantly different between the pre-
      and post-operations both in the laparoscopic group and the laparotomic
      group(P>0.05),and there was also no significant difference between the
      laparoscopic group and the laparotomic group(P>0.05).The follow-up period in the
      laparoscopic group was 7 approximately 19 (14.25+/-3.65) months and 7
      approximately 19 (13.10+/-4.23) months in the laparotomic group. One patient got
      infection in the urinary system in the laparoscopic group and one patient had
      lower extremity venous thrombosis in the laparoscopic group.No recurrence was
      detected in both groups. CONCLUSION: Laparoscopic surgery for endometrial cancer
      has no effect on protein expressions of E-cadherin,beta-catenin,P-selectin,MMP
      2,VEGF,and CD44v6 in tumor tissues. No evidence has been found that CO2
      pneumoperitoneum-laparoscopic surgery may favor endometrial cancer cell seeding
      and metastases.

PMID- 18326908
TI  - [Differentiation of 2 endothelial progenitor cells in vitro and inhibitory effect
      of asymmetric dimethylarginine on its proliferation].
AB  - OBJECTIVE: To investigate the Methods for culturing two types of endothelial
      progenitor cells (EPC) from human umbilical cord blood and study their
      differentiation traits and the depressant effect of asymmetric dimethylarginine
      (ADMA) on its proliferation. METHODS: Mononuclear cells were isolated from fresh
      cord blood by 6% hydroxyethyl starch(HES) and density gradient
      centrifugation.Isolated cells were cultured in the medium supplemented with
      vascular endothelial growth factors (VEGF) and basic fibroblast growth factors
      (bFGF). The growth characteristics and biological features of the cells were
      observed at different time points and identified by morphology,immunofluorescence
      staining,reverse transcription polymerase chain reaction (RT-PCR), and flow
      cytometry.Attached cells were incubated with different concentrations of ADMA
      (1,5, and 10 micromol/L) for 24,48, and 72 hours. Methylthiazoletetrazolium (MTT)
      assay and quantified colony forming units (CFUs) were used to assess the
      proliferation of endothelial progenitor cells. RESULTS: The attached cells were
      divided into 2 types:early EPC and late EPC. Early EPC changed from small sized
      round cells to spindle shaped cells and late EPC formed a typical cobblestone
      like cells. Fluorescence microscopy showed that EPC were positive for both Dil
      acLDL uptake and FITC-UEA-I binding.RT-PCR and FACS showed the difference of
      endothelial cell-specific,gene expression and changed AC133,CD34, and KDR among
      different times.Incubation of EPC with ADMA dose and time-dependently decreased
      the number and the proliferation of EPC. CONCLUSION: There are 2 types of EPC
      from a source of human umbilical cord blood and ADMA may depress the EPC
      proliferation, providing a basis for further research.

PMID- 18326909
TI  - [Effect of isoflurane delayed preconditioning on myocardial ischemia reperfusion
      injury in rabbits].
AB  - OBJECTIVE: To investigate the protective effect of isoflurane delayed
      preconditioning on myocardial ischemia reperfusion injury and the potential
      mechanism in rabbits. METHODS: Thirty New Zealand male white rabbits were
      randomly assigned to 3 groups: Control group; I/R group; and 2.0% isoflurane
      group. Isoflurane group was exposed to 2.0% isoflurane-100% oxygen for 2 hours.
      Control group and I/R group were exposed to 100% oxygen for 2 hours and served as
      untreated controls. Twenty-four hours later I/R group and isoflurane group
      underwent 40 minutes of coronary occlusion followed by 2 hours of reperfusion.
      Blood samples were taken from the arterial line at 20 minutes before the
      occlusion(T1), 20 minutes after the occlusion(T2), 40 minutes after the
      occlusion(T3), 1 hours after the reperfusion(T4), and 2 hours after the
      reperfusion(T5) to determine the plasma level of TNF-alpha. At the end of the
      reperfusion, infarct size and area at risk were defined by Evans and TTC
      staining. The heart was harvested and levels of the p38MAPK activity were
      determined by Western blot, and ultrastructures were observed under the electron
      microscope. RESULTS: The p38MAPK activity of isoflurane group was significantly
      lower than that of I/R group (P<0.05). Isoflurane significantly (P<0.05) reduced
      the infarct size(19.7%+/-2.8% in isoflurane group) of the left ventricular area
      at risk as compared with the controls (37.8%+/-1.7% in I/R group).The injury of
      I/R group was worse than that of isoflurane group under the light microscope.
      Isoflurane group had a lower level of TNF-alpha than I/R group. CONCLUSION:
      Isoflurane can inhibit p38MAPK activity during myocardial ischemia reperfusion
      and modulate the cytokine expression, which may be one of the molecular
      mechanisms of isoflurane delayed preconditioning on cardioprotection.

PMID- 18326910
TI  - [Clinical characteristics and prognostic factors in 73 patients with peripheral T
      cell lymphoma].
AB  - OBJECTIVE: To investigate the clinical features,therapy and prognosis of patients
      with peripheral T cell lymphoma(PTCL), and to find out the prognostic factors of
      the disease. METHODS: The clinical data of 73 patients with PTCL were
      reviewed.The median pre-treatment disease course was 3 months.Fifty-five patients
      were males, and 18 were females, with the median age of 42 years.Five patients
      received the combined chemo-radio therapy, 65 received chemotherapy alone, and
      the other 3 patients were treated with auto hematopoietic stem cell
      transplantation (HSCT). RESULTS: Of all the patients, the overall 3 -year and 5
      year survival rates were 38% (28 /73) and 22% ( 16 /73) respectively.The survival
      rates decreased with the progression of the Ann Arbor stages.The survival rate of
      the patients with B symptom (fever, night sweat, and weight loss) or the
      international prognostic factors index ( IPI)>2 was lower than those of the
      patients without B symptom or IPI<2.The patients with the increased CA125 or D
      dimer lever had the worst curative effect. CONCLUSION: Peripheral T cell lymphoma
      is highly aggressive with poor prognosis.The clinical features,Ann Arbor staging,
      IPI and B symptom are important prognostic factors.CA125 and D-dimer may be also
      important prognostic factors.

PMID- 18326911
TI  - [Fifty-three cases of valve repair for mitral insufficiency].
AB  - OBJECTIVE: To summarize the experience of mitral vavuloplasty for mitral
      insufficiency in 53 patients. METHODS: Between January 2001 and September 2006,53
      patients (31 males and 22 females) with mitral insufficiency underwent mitral
      valve repair at our hospital. The mean age was (23.8+/-10.4) years, and the mean
      weight was (43+/-12) kg,including 29 cases of mitral prolapse,17 congenital
      mitral insufficiency, 5 rheumatic mitral insufficiency,and 2 other etiology. All
      operations were performed under cardiopulmonary bypass,moderate hypothermia and
      under the surveillance of transesophagus echocardiography. RESULTS: There were 2
      early postoperative deaths,and another patient failed to repair and received
      valve replacement afterward. Postoperative echocardiography indicated that mitral
      insufficiency was completely corrected in 42 patients, and residual mitral
      regurginitation in the other 8 patients. During the follow-up with mean period
      13.8 months,41 patients revealed 28 in NYHA classI,13 in Class II. CONCLUSION:
      Mitral valve repair should be the preferred modes of surgical correction for
      regurgitate mitral valves. With proper vavuloplasty technique, patients with
      selective mitral insufficiency patients may achieve satisfactory effect.

PMID- 18326912
TI  - [Quantitative ultrasonic integrated backscatter of the intima-media complex,
      serum level of matrix metalloprotease-9 and simvastatin in hyperlipemia
      patients].
AB  - OBJECTIVE: To determine the diagnostic value of the integrated backscatter (IBS)
      technique for carotid artery atherosclerosis (AS), to investigate the correlation
      between IBS of carotid artery and the serum level of matrix metalloprotease-9(MMP
      9), and to explore the effect of simvastatin on the IBS value of the carotid
      artery and serum MMP-9 level in hyperlipemia patients. METHODS: Fifty-eight
      patients with hyperlipemia and 26 normal controls were enrolled in this study.
      Patients with hyperlipemia were randomly divided into 2 groups: a simvastatin
      treatment group (20 mg/d) and a control group (without simvastatin treatment).
      Twenty-six healthy people were served as normal control group(n=26).The corrected
      IBS values(C-IBS) in carotid arteries,the intima-media thickness (IMT), and the
      serum MMP-9 levels were measured in the normal control group and the patients
      with hyperlipemia before and 8 weeks after the simvastatin therapy. RESULTS: The
      C-IBS of the simvastatin treatment group and the control group was significantly
      lower than that in the normal control group (all P<0.05). The IMT and MMP-9 in
      the simvastatin treatment group and the control group were significantly higher
      than those in the normal control group (all P<0.05). There was a negative
      correlation between the C-IBS of carotid arteries and the serum MMP-9 levels in
      the patients with hyperlipemia (r=-0.76,P<0.05). Eight weeks after the
      simvastatin treatment, the serum MMP-9 levels decreased significantly(P<0.05).
      CONCLUSION: There is a negative correlation between the decreased C-IBS of
      carotid arteries and the increased serum MMP-9 levels in patients with
      hyperlipemia.The decreased C-IBS of carotid arteries and the increased serum MMP
      9 levels may be the early indicators of atherosclerosis in hyperlipemia patients.
      The anti-atherosclerosis effect of simvastatin may partly attribute to its
      ability to lower the serum MMP-9.

PMID- 18326913
TI  - [Novel frame-shift mutation of 540 A deletion in GP IIb gene from a patient with
      Glanzmann thrombasthenia].
AB  - OBJECTIVE: To explore the molecular mechanism of Glanzmann thrombasthenia (GT).
      METHODS: All 45 exons of alphaIIb and beta3 subunit genes as well as their
      splicing sites were amplified by polymerase chain reaction(PCR) with 40 primer
      pairs, and then the PCR products were used to screen the gene mutation by single
      strand conformation polymorphism-polyacrylamide gel electrophoresis (SSCP-PAGE).
      The mutation was further confirmed by direct DNA sequencing. RESULTS: A DNA band
      alterated migration was detected after SSCP-PAGE. DNA sequencing showed that a
      base deletion within the band at the site of 540 in GPIIb gene(540A) was found.
      CONCLUSION: The frame-shift mutation caused by the deletion of 540A in GPIIb gene
      is a novel mutation which is a genetic defect in patients with GT.

PMID- 18326914
TI  - [Effect of IL-10 on LOX-1 expression of peripheral blood monocytes in patients
      with acute coronary syndrome].
AB  - OBJECTIVE: To determine the expression of lectin-like oxidized low-density
      lipoprotein receptor-1 (LOX-1) of peripheral blood monocytes in patients with
      acute coronary syndromes (ACS),and to further explore the effect of anti
      inflammatory factor interleukin-10 (IL-10) on the expression of LOX-1. METHODS:
      Twenty-eight healthy controls and 28 ACS patients were enrolled in the study. The
      levels of IL-10 and tumor necrosis factor (TNF-alpha) were determined by enzyme
      linked immunosorbnent assay(ELISA). The monocytes of peripheral blood in patients
      and controls were isolated and incubated with exogenous IL-10 (20 microg/L). The
      expression of LOX-1 protein and mRNA in the monocytes was examined by Western
      blot and reverse transcriptase PCR (RT-PCR). RESULTS: Compared with the healthy
      controls, the levels of serum IL-10 and TNF-alpha were significantly elevated in
      ACS patients (P<0.01). The expression of LOX-1 protein and mRNA was markedly
      upregulated in the isolated monocytes from ACS patients, which could be
      downregulated by IL-10 (20 microg/L, 3 h) (P<0.01). CONCLUSION: The effect of
      anti-inflammatory factor IL-10 on the atherosclerosis may be a new mechanism
      resulting in plaque stabilization via the decreased LOX-1 expression of
      peripheral monocytes in ACS patients.

PMID- 18326915
TI  - [Effect of Twist gene on the migration and invasion of gastric carcinoma cells].
AB  - OBJECTIVE: To explore the effect of Twist gene on the migration and invasion of
      human gastric carcinoma cells. METHODS: MKN28 cells, a human gastric carcinoma
      cell line, were transfected with PcDNA3.1-Twist plasmid by lipofectamine
      transfecting technique. The transfected cells were selected with geneticin.
      Expressions of Twist,ecadherin and vimentin protein were detected by Western blot
      in cells transfected Twist gene. Matrigel invision chambers were performed to
      analyse the cell migration and invasion. RESULTS: MKN28 cells transfected with
      PcDNA3.1-Twist plasmid showed stronger intracellular expression of Twist protein
      than MKN28 cells transfected with PcDNA3.1 and MKN28 cells without transfection.
      The expression of ecadherin protein in MKN28 cells transfected with PcDNA3.1
      Twist plasmid was significantly decreased compared with that in MKN28 cells
      transfected with PcDNA3.1 and MKN28 cells without the transfection. However, The
      expression of vimentin protein in MKN28 cells transfected with PcDNA3.1-Twist
      plasmid was significantly increased compared with that in MKN28 cells transfected
      with PcDNA3.1 and MKN28 cells without transfection. The migration and invasion
      ability of Twist+ - MKN28 cells were stronger than that of MKN28 cells
      transfected with PcDNA3.1 and MKN28 cells without transfection. CONCLUSION: Twist
      gene may promote the migration and invasion ability of gastric carcinoma cells
      through epithelial mesenchymal transition.

PMID- 18326916
TI  - [Clinical significance of rapid increase of heart rate at onset of treadmill
      exercise test].
AB  - OBJECTIVE: To analyze the correlation between rapid increase of heart rate at
      onset of electrocardiogram treadmill exercise test and coronary artery lesion.
      METHODS: We selected 245 patients who underwent electrocardiogram treadmill
      exercise and coronary angiography. The patients were divided into a coronary
      heart disease (CHD) group and a non-CHD group according to the Results of
      coronary angiography. The patients of the CHD group were divided into a single
      vessel disease group, a double-vessel disease group, and a triplet-vessel disease
      group. The increased heart rate during the first minute (DeltaHR 1minute) of
      treadmill exercise test and the extent of coronary artery lesion were analyzed.
      RESULTS: DeltaHR 1minute in the CHD group was significantly higher than that in
      the non-CHD group(P<0.01). DeltaHR 1minute had an increasing trend with the
      severity of coronary artery lesion. DeltaHR 1minute was positively correlated to
      the depression of ST segment and the severity of coronary artery
      lesion(r=0.252,0.470, P<0.01). CONCLUSION: Patients with CHD have an increased
      DeltaHR 1minute. DeltaHR 1minute can be one of the indexes to estimate the extent
      of myocardial ischemia and coronary artery lesion.

PMID- 18326917
TI  - [Surgical treatment of 72 cases of ascending aortic aneurysm].
AB  - OBJECTIVE: To summarize the experience of clinical diagnosis and surgical
      treatment of ascending aortic aneurysm. METHODS: The clinical data of 72 cases of
      ascending aortic aneurysm were retrospectively analyzed. Of the 72 cases, 36
      suffered Mafanos syndrome, 35 suffered aortic dissection, and 1 multiple aortic
      pseudo-aneurysm. All the patients received artificial vessel replacement or
      repair under middle or low temperature of cardiopulmonary bypass. Two patients
      received coronary artery bypass grafting, 2 received aortic valve replacement,and
      1 received artificial patch repair. RESULTS: Eight patients died and the others
      recovered without nervous system complications and were discharged. CONCLUSION:
      Expedient confirmatory diagnosis, prompt surgical therapy, and efficient therapy
      during the peri-operative period are helpful to achieve a successful outcome.

PMID- 18326918
TI  - Optimal second line treatment options for gemcitabine refractory advanced
      pancreatic cancer patients. Can we establish standard of care with available
      data?

PMID- 18326919
TI  - Is there a standard of care for the management of advanced pancreatic cancer?.
      Highlights from the Gastrointestinal Cancers Symposium. Orlando, FL, USA. January
      25-27, 2008.
AB  - Despite advances in our understanding of the molecular and genetic basis of
      pancreatic cancer, the outcome for this disease remains dismal. Gemcitabine, the
      standard chemotherapy for pancreatic cancer, offers modest improvement of tumor
      related symptoms and marginal advantage of survival. Many chemotherapeutic and
      targeted agents have been pitted against or combined with gemcitabine in
      randomized phase III trials and no drug was shown to be superior to single-agent
      gemcitabine except two gemcitabine-containing combinations: capecitabine plus
      gemcitabine vs. gemcitabine and erlotinib. In this article, the author debates:
      "Is there a standard of care for the treatment of advanced pancreatic cancer?".
      In addition, he summarizes the key studies presented at the "Gastrointestinal
      Cancers Symposium" held in Orlando, FL, USA on January 25-27, 2008. The studies
      discussed here include the following: i) a phase I study of a chemotherapy
      doublet gemcitabine plus capecitabine, combined with a biologic doublet
      (bevacizumab plus erlotinib) in patients with advanced pancreatic adenocarcinoma
      (abstract #141); ii) a phase II study of gemcitabine, bevacizumab, and erlotinib
      in locally advanced and metastatic adenocarcinoma of the pancreas (abstract
      #151); iii) final results of the multicenter phase II study on gemcitabine,
      capecitabine, and bevacizumab in patients with advanced pancreatic cancer
      (abstract #198); iv) interim results from a phase II study of volociximab in
      combination with gemcitabine in patients with metastatic pancreatic cancer
      (abstract #142); v) a pilot study of combination chemotherapy with S-1 and
      irinotecan for advanced pancreatic cancer (abstract #155); vi) a multicenter
      phase II study of gemcitabine and S-1 combination chemotherapy in patients with
      unresectable pancreatic cancer (abstract #212); vii) a phase I/II study of PHY906
      plus capecitabine in patients with advanced pancreatic carcinoma (abstract #260);
      and viii) the final results of a phase II trial of Genexol-PM(R), a novel
      cremophor-free, polymeric micelle formulation of paclitaxel in patients with
      advanced pancreatic cancer (abstract #269). Based on the results presented at the
      meeting, it comes to us that patients with locally advanced vs. metastatic
      pancreatic cancer should be studied separately, better understanding of the
      biology of pancreatic cancer is mandatory and evaluation of novel agents is
      crucial. We, as oncologist, have to change our attitudes towards clinical trials
      and need to think beyond a trial design such as gemcitabine vs. drug of our
      choice.

PMID- 18326920
TI  - Survival following curative resection for pancreatic ductal adenocarcinoma. A
      systematic review of the literature.
AB  - CONTEXT: Patients with resectable pancreatic cancer comprise a small subgroup of
      the overall population with the disease from around 15 to 20%, with nearly all
      patients dying from their disease within 7 years of surgery. In the light of such
      bleak statistics, data regarding what factors may influence outcome, following
      attempted curative resection is essential in order to optimise the treatment
      options for patients. METHODS: This review analysed all English-language
      publications using PubMed and Web of Science databases for studies detailing
      outcomes following resection for pancreatic ductal adenocarcinoma from 1980 to
      the present day. MAIN OUTCOME MEASURES: The data examined from papers were post
      operative mortality rates, median survival, yearly survival rates and other
      factors which may have influenced long-term survival; such as patient
      demographics, operative details and tumour characteristics (such as example
      tumour size, lymph node metastases and tumour differentiation). RESULTS: There
      has been significant improvement in post-operative mortality over the last
      decades with a modest improvement in long-term survival. With the exception of
      post-operative blood transfusion, tumour characteristics remain the only
      significant features influencing survival after pancreatic cancer surgery.
      Favourable prognostic factors include tumour size less than 2 cm, negative
      resection margin, lymph node negative tumours, well-differentiated tumours and
      absence of perineural or blood vessel invasion. CONCLUSION: In light of these
      data, it could be reasoned that tumour size, on cross-sectional imaging, might be
      employed as means of selecting the most appropriate candidates for surgery, in
      cases where the risks of resection are high.

PMID- 18326921
TI  - Expression and hypoxic regulation of the endothelin system in endocrine cells of
      human and rat pancreatic islets.
AB  - CONTEXT: The success of pancreatic islet transplantation depends largely on the
      capacity of the islet graft to survive the initial phase immediately after
      transplantation until revascularization is completed. Endothelin-1 (ET-1) is a
      strong vasoconstrictor which has been involved in solid organ graft failure but
      is also known to be a potent mitogenic/anti-apoptotic factor which could also
      potentially enhance the survival of the transplanted islets. OBJECTIVE:
      Characterization of the endothelin system with regard to a potential endothelin
      agonist/antagonist treatment. DESIGN: Regulated expression of the endothelin
      system in human and rat pancreatic islets and beta-cell lines was assessed by
      means of immunohistochemistry, competition binding studies, western blot, RT-PCR,
      real-time PCR and transplant studies. RESULTS: ET-1, ETA- and ETB-receptor
      immunoreactivity was identified in the endocrine cells of human and rat
      pancreatic islets. The corresponding mRNA was detectable in rat beta-cell lines
      and isolated rat and human pancreatic islets. Competition binding studies on rat
      islets revealed binding sites for both receptor types. ET-1 stimulated the
      phosphorylation of mitogen-activated protein kinase, which was prevented by ETA-
      and ETB-receptor antagonists. After exposure to hypoxia equal to post-transplant
      environment oxygen tension, mRNA levels of ET-1 and ETB-receptor of human islets
      were robustly induced whereas ETA-receptor mRNA did not show significant changes.
      Immunostaining signals for ET-1 and ETA-receptor of transplanted rat islets were
      markedly decreased when compared to native pancreatic sections. CONCLUSIONS: In
      pancreatic islets, ET-1 and its receptors are differentially expressed by hypoxia
      and after transplantation. Our results provide the biological basis for the study
      of the potential use of endothelin agonists/antagonists to improve islet
      transplantation outcome.

PMID- 18326922
TI  - Three cases of unusual solid pseudopapillary tumors. Can radiology and histology
      aid decision-making?
AB  - CONTEXT: Solid pseudopapillary tumors of the pancreas are generally considered to
      be of low malignant potential despite their often large size at presentation. The
      diagnosis of a solid pseudopapillary tumor depends on the characteristic
      histomorphology supported by immunohistochemistry. The tendency of some of these
      tumors to be locally aggressive and also to metastasize has been well recognized.
      It is not possible to predict the biologic behavior of these tumors based only on
      their morphology. METHODS: The hospital database including the radiological
      records and histopathology of patients with metastatic solid pseudopapillary
      tumors, treated at the Tata Memorial Hospital between January 2006 and May 2007
      were retrospectively reviewed. RESULTS: The clinical details, radiological
      features and histopathology of three cases of unusually aggressive solid
      pseudopapillary tumors are presented. CONCLUSIONS: It is important to recognize
      that solid pseudopapillary tumors may present or recur as locally invasive as
      well as widely metastatic lesions. While clinical presentation and radiology
      demonstrate an aggressive disease, it may still be difficult to prove its
      malignant potential on conventional histomorphological grounds. In spite of the
      presence of local invasion and metastasis, long term survival is possible and
      complete excision should be attempted.

PMID- 18326923
TI  - Emphysematous pancreatitis. Radiological curiosity or a cause for concern?
AB  - CONTEXT: Emphysematous pancreatitis is a rare, potentially fatal variant of
      severe acute pancreatitis with gas in the pancreatic bed. There are isolated case
      reports describing this condition. OBJECTIVE: This report summarizes our
      experience with the management of this condition in order to compare its clinical
      characteristics, microbiological and radiological features, surgical management
      and the outcome of patients with emphysematous pancreatitis and non-emphysematous
      infected pancreatic necrosis. SETTING: The hospital records of the patients who
      underwent necrosectomy for infected pancreatic necrosis between 2002 and 2006
      were reviewed. PATIENTS: Fifty-seven patients were identified: 11 of them (19.3%)
      had gas in and around the pancreas on computed tomography and 46 (80.7%) had non
      emphysematous infected pancreatic necrosis. MAIN OUTCOME MEASURES: The clinical
      characteristics and the hospital course of the two groups of patients were
      compared. RESULTS: The mean age of 11 patients with emphysematous pancreatitis
      was 34.0+/-11.5 years and alcohol was the most common etiology (54.5%). The
      median computed tomography severity index was 10. All 11 patients with
      emphysematous pancreatitis had growth of organisms on culture of fine needle
      aspiration or pancreatic tissue obtained at surgery, with Escherichia coli in all
      of them. Polymicrobial infection was seen in 5 (45.5%) of them. In comparing
      patients having emphysematous pancreatitis with those having non-emphysematous
      infected necrosis, there was no significant difference in the severity of the
      disease (P=0.319), time to surgical intervention (P=0.553), incidence of organ
      failure (P=0.297), hospital stay (P=0.580) or mortality rate (P=0.739). The total
      number of locoregional complications was significantly higher in patients with
      emphysematous pancreatitis (P=0.049). However, when compared separately, the
      incidence of enteric fistula, bleeding, intra-abdominal collections and wound
      complications were similar in the two groups (P>0.250). CONCLUSION: Emphysematous
      pancreatitis is easily diagnosed on computed tomography and all patients require
      surgical intervention. The clinical course and prognosis is not different from
      that of infected pancreatic necrosis.

PMID- 18326924
TI  - Clinical utility of endoscopic ultrasound in solid pancreatic mass lesions deemed
      resectable by computer tomography.
AB  - CONTEXT: Appropriate surgical exploration and resection of pancreatic carcinoma
      depends on accurate preoperative evaluation. OBJECTIVE: Determine the accuracy of
      endoscopic ultrasound in predicting the need for surgical exploration in patients
      with solid pancreatic masses deemed by computer tomography to be resectable
      without venous grafting (absence of distant metastatic disease or major vascular
      involvement). PATIENTS: All patients between March 2000 and November 2003 with
      focal pancreatic mass lesions deemed to be surgically resectable by computer
      tomography. Forty-nine patients participated (29 males, 20 females; age range: 40
      86 years). INTERVENTION: Preoperative linear-array endoscopic ultrasound. MAIN
      OUTCOME MEASURE: Surgical pathology compared to computer tomography and
      endoscopic ultrasound results. RESULTS: Out of the 49 patients, 33 (67.3%) had
      pancreatic neoplasms and 16 (32.7%) had chronic pancreatitis. Endoscopic
      ultrasound correctly diagnosed all 16 patients with chronic pancreatitis.
      Endoscopic ultrasound correctly identified 18 (54.5%) of those with neoplasms as
      having unresectable disease while 6 (18.2%) patients were appropriately
      identified as resectable by endoscopic ultrasound. The remaining 9 patients
      (27.3%) were deemed resectable by endoscopic ultrasound, but were unresectable at
      the time of surgery. None of the patients were falsely designated as unresectable
      by endoscopic ultrasound. CONCLUSION: Endoscopic ultrasound is an important
      compliment to computed tomography in predicting resectability and in avoiding
      nontherapeutic laparotomy of solid pancreatic neoplasms. Moreover, endoscopic
      ultrasound classification did not discourage surgery of resectable pancreatic
      masses.

PMID- 18326925
TI  - Management of delayed arterial hemorrhage after pancreaticoduodenectomy. A case
      series.
AB  - CONTEXT Delayed arterial hemorrhage is a rare complication after
      pancreaticoduodenectomy (frequency 2-4%) but carries a high mortality, with up to
      a third of patients dying as a consequence. Its ideal management remains unclear.
      CASE SERIES: Between 1993 and 2007, 317 head of pancreas resections were
      performed at our institution; there were 5 cases of delayed arterial hemorrhage
      (frequency 1.6%). CONCLUSION: This paper presents our experience in the
      management of delayed arterial haemorrhage post pancreaticoduodenecomy and
      discusses the role of angiograms, endoscopy and laparotomy in its management.

PMID- 18326926
TI  - Utilization of intensive care unit resources in severe acute pancreatitis.
AB  - CONTEXT: Severe acute pancreatitis is a common abdominal emergency; it is a
      potentially fulminant disease with no specific treatment. The incidence of severe
      acute pancreatitis is increasing, but the overall population mortality rate has
      remained unchanged as the case fatality rate has decreased over time. The
      hospital mortality rate of patients with severe acute pancreatitis has dropped to
      20% even in the most severe forms of the disease. The prolonged course of severe
      acute pancreatitis, associated with multi-organ failure and other complications,
      is a considerable strain on intensive care unit (ICU) resources. OBJECTIVE: To
      analyze the extent of ICU resources consumed by the severe acute pancreatitis
      patient group as well as the expenses of the treatment and differences in the
      costs of survivors versus patients who die after a prolonged stay in the ICU.
      DESIGN: Retrospective study. PARTICIPANTS: All patients with severe acute
      pancreatitis treated in the general ICU of Helsinki University Hospital from 1995
      to 2005 (245 patients; 169 (69.0%) with alcohol-induced severe acute
      pancreatitis). RESULTS: The mean length of the ICU stay was 17.4 days and severe
      acute pancreatitis patients constituted 17.0% of all ICU days. The mean hospital
      cost per patient was 86,856 Euros. The overall mortality rate was 26.1% and the
      hospital costs of the non-survivors seemed to be higher (although not
      significantly) than that of the survivors. CONCLUSIONS: Optimal early care in
      order to decrease the onset of organ dysfunctions and better prognostic models to
      identify non-surviving severe acute pancreatitis patients earlier could lead to
      considerable savings in the overall use of ICU resources.

PMID- 18326927
TI  - Long term survival on S-1 monotherapy in a patient with recurrent stage IV
      pancreatic cancer.
AB  - CONTEXT: Pancreatic cancer is the third most common gastrointestinal malignancy
      in the United States. Due to difficulty in diagnosis, 40% of patients are stage
      IV by the time of diagnosis and median survival is only four to six months.
      Current therapy for advanced pancreatic cancer focuses largely on gemcitabine.
      However, a relatively new drug, S-1, is showing promising results. Phase II
      studies of S-1 monotherapy and recent combination with gemcitabine were conducted
      for the treatment of metastatic pancreatic cancer. The early phase II study
      demonstrated a response rate approaching 20% while the combination is reaching
      more than 35%. CASE REPORT: We report a 68-year-old man who presented with stage
      IIB pancreatic cancer which advanced to stage IV after undergoing a Whipple
      procedure and adjuvant treatment with gemcitabine. The patient was refractory to
      treatment with gemcitabine as well as irinotecan, taxotere, and cetuximab. He
      subsequently participated in a trial involving the drug S-1. He achieved 10-month
      survival with preserved quality of life: he had 14 cycles of S-1 and maintained
      an ECOG performance status of 0-1 throughout. CONCLUSION: For this patient, 14
      cycles of S-1 were well-tolerated for 10 months after failing two prior
      chemotherapeutic regimens suggesting important insight that S-1 may be active and
      convenient for its oral use and it may have favorable safety profile in patients
      with metastatic pancreatic cancer. Randomized trials are warranted to determine
      the effectiveness of S-1 for the treatment of pancreatic cancer.

PMID- 18326928
TI  - Diagnosis of pancreatic gastrointestinal stromal tumor by EUS guided FNA.
AB  - CONTEXT: Gastrointestinal stromal tumors of the pancreas are very rare. Only two
      case reports have been published, both with diagnoses made on surgical pathology.
      We present the first case of pancreatic stromal tumor diagnosed by endoscopic
      ultrasound guided fine needle aspiration. CASE REPORT: A 47-year-old male
      presented with self limited nausea and vomiting. A CT scan revealed a subtle,
      hypervascular mass in the uncinate process of the pancreas. Endoscopic ultrasound
      confirmed the pancreatic mass and fine needle aspiration was performed giving a
      bloody sample. Cytology showed spindle cell proliferation with CD117 positive
      immunohistochemistry, confirming a pancreatic gastrointestinal stromal tumor.
      CONCLUSION: We present a case of pancreatic stromal tumor diagnosed by endoscopic
      ultrasound guided fine needle aspiration. Although very rare in the pancreas,
      gastrointestinal stromal tumors should be considered in the differential
      diagnosis of solid pancreatic masses and blood aspirates.

PMID- 18326929
TI  - Rechallenge with cisplatin in a patient with pancreatic cancer who developed a
      hypersensitivity reaction to oxaliplatin. Is skin test useful in this setting?
AB  - CONTEXT: A recent meta-analysis suggests that the addition of oxaliplatin or
      cisplatin to gemcitabine can lead to improved survival in patients with advanced
      pancreatic cancer, especially those with a good performance status. In an event
      of a platinum hypersensitivity reaction, the particular platinum salt is likely
      discontinued. Desensitization has shown benefit anecdotically but it is an
      intensive process. We present a case in which platinum-containing therapy was
      able to continue in a patient with metastatic pancreatic cancer following a
      hypersensitivity reaction to oxaliplatin, by switching to cisplatin after a
      negative intradermal skin test. CASE REPORT: A 58-year-old gentleman with
      metastatic pancreatic adenocarcinoma received biweekly cycles of gemcitabine in
      combination with oxaliplatin. During the fifth cycle, he experienced a grade 2
      hypersensitivity reaction including erythema and lip numbness, for which he was
      medicated with antihistaminics and corticosteroids. Cycles 6 and 7 of oxaliplatin
      were tolerated over 4 h infusion with pretreatment of H1, H2 blockers and
      corticosteroids. During the 8th cycle, the patient developed a grade 3
      hypersensitivity reaction manifesting as facial flushing, sweating, symptomatic
      bronchospasm, cyanotic lips and chest tightness. Symptoms resolved with
      antihistaminics, corticosteroids and epinephrine. Although oxaliplatin treatment
      was discontinued, the patient's response to the platinum therapy merited a
      cisplatin rechallenge. An intradermal skin test was administered with negative
      result, allowing for a regimen change to biweekly gemcitabine and cisplatin. The
      patient has tolerated multiple additional cycles with further decrease in tumor
      size and tumor markers. CONCLUSIONS: Intradermal skin tests can be useful tools
      for effectual rechallenge. Literature review reveals scarce data of intradermal
      skin tests used to rechallenge cisplatin to patients with oxaliplatin
      hypersensitivity reaction, and our case is the first apparent example for a
      patient with advanced pancreatic cancer. Despite the possibility of platinum
      cross-reactivity, rechallenge can be considered if patients have responded to the
      therapy and are treated in a supervised environment.

PMID- 18326930
TI  - Cytological features of the cystic fluid of pancreatic schwannoma with cystic
      degeneration. A case report.
AB  - CONTEXT: Schwannomas are benign neoplasms arising from peripheral nerve tissue.
      Pancreatic schwannoma is a very rare condition. We present the histological and
      cytological features of a pancreatic schwannoma with cystic degeneration. CASE
      REPORT: A 51-year-old male was diagnosed with a cystic tumor measuring
      approximately 6 cm in the tail of the pancreas. Distal pancreatectomy and
      splenectomy were performed. Cystic fluid from the tumor was obtained
      intraoperatively by fine-needle aspiration, and it showed scattered spindle tumor
      cells against a background of hemosiderin-laden histiocytes. During the
      operation, we informed the surgeon that the tumor consisted of "atypical spindle
      cells". Histologically, the tumor was diagnosed as a schwannoma with cystic
      degeneration which had originated in the pancreas. The diagnosis was confirmed by
      positive immunostaining of the tumor cells in both histological and cytological
      materials for S-100 protein. CONCLUSION: Problems occasionally arise with the use
      of fine-needle aspiration in the diagnosis of cystic diseases of the pancreas
      because of the difficulty in obtaining adequate specimens. Nevertheless, it
      should be emphasized that intraoperative fine-needle aspiration is as informative
      as a frozen section diagnosis, when appropriately performed.

PMID- 18326931
TI  - Biochemical investigation is no substitute for clinical examination!
AB  - CONTEXT: Toxic shock syndrome has been shown previously to be associated with
      hyperamylasaemia. However, serum amylase levels do not usually exceed three times
      upper limit of normal in these cases. CASE REPORT: We report a case of a young
      girl of 17 years who presented with upper abdominal pain, severe shock and raised
      serum amylase level of 3,898 U/L, giving an impression of severe acute
      pancreatitis. It was only after finding a tampon in her vagina, and subsequently
      growing Staphylococcus aureus in her blood cultures, did the diagnosis of toxic
      shock syndrome become apparent. She recovered fully with supportive treatment and
      appropriate antibiotics. CONCLUSIONS: Toxic shock syndrome with such a high level
      of serum amylase has not been previously reported. This case exemplifies the
      importance of repeated clinical evaluation of patients in this era of multiple
      investigations, and not simply relying on biochemical values for diagnosis.

PMID- 18326932
TI  - Papillary adenoma of the distal common bile duct associated with a synchronous
      carcinoma of the peri-ampullary duodenum.
AB  - CONTEXT: Benign tumours of the biliary tract are an extremely rare group of
      neoplasms. The diagnosis of these rare tumours is established on
      histopathological analysis following resection. Coincidence of a biliary adenoma
      of the distal common bile duct and a synchronous adenocarcinoma of the peri
      ampullary duodenum has never been reported in the literature. CASE REPORT: We
      report a case of a papillary adenoma in the common bile duct in a 75-year-old
      female, who had synchronous invasive adenocarcinoma of the peri-ampullary
      duodenum. CONCLUSION: Isolated papillary adenoma of the bile duct is extremely
      rare, and in this unusual case it coincided with a peri-ampullary duodenal
      adenocarcinoma. However, this is a rare instance of an incidental finding within
      the distal bile duct following pancreaticoduodenectomy for curative treatment of
      a peri-ampullary adenocarcinoma.

PMID- 18326933
TI  - Erlotinib-induced episcleritis in a patient with pancreatic cancer.
AB  - CONTEXT: Erlotinib is a relatively new anilinoquinazoline indicated for treatment
      of pancreatic cancer in combination with gemcitabine. It is a tyrosine kinase
      inhibitor that specifically targets epidermal growth factor receptor (EGFR),
      which is commonly overexpressed and/or mutated in solid tumors. Active
      competitive inhibition of adenosine triphosphate, inhibits downstream signal
      transduction of ligand dependent EGFR activation. EGFR kinase inhibitors are less
      toxic than conventional chemotherapy as they are relatively specific for tumor
      cells. Common side effects include acneiform (papulopustular) rash, diarrhea,
      edema, pruritus, dry skin and alopecia. CASE REPORT: This article reports the
      case of a 55-year-old Caucasian female with recurrent pancreatic cancer who
      developed episcleritis after seventeen days of treatment with erlotinib. Symptoms
      completely resolved four weeks after drug discontinuation. CONCLUSIONS: To our
      knowledge, erlotinib-induced episcleritis has not been previously described.

PMID- 18326934
TI  - Virtual MR pancreatoscopy in the evaluation of the pancreatic duct in chronic
      pancreatitis.
AB  - The main pancreatic duct and the common bile duct can be evaluated with a variety
      of evolving invasive and non-invasive techniques. Virtual CT pancreatoscopy
      obtained using special computer software is a recent non-invasive innovation
      which shows the details of the ductal surface (endoluminal view) with greater
      precision. The use of special computer software in MRI in order to obtain
      pancreatic ductal surface details or a virtual MR pancreatoscopy has not been
      described up to now. We report a short series of four patients suffering from
      chronic pancreatitis who underwent virtual MR pancreatoscopy with an impact on
      their management and clinical outcome.

PMID- 18326935
TI  - Atypical toxicity associated with 5-Fluororacil in a DPD-deficient patient with
      pancreatic cancer. Is ethnicity a risk factor?
AB  - CONTEXT: Fluoropyrimidines constitute the backbone of chemotherapy regimens for
      GI tumors, including pancreatic cancer where it is used either as a
      radiosensitizer or as second-line after failing gemcitabine. While normal
      dihydropyrimidine dehydrogenase (DPD) enzyme activity is rate limiting in 5
      fluorouracil (5-FU) catabolism, its deficiency could increase concentrations of
      bioavailable 5-FU anabolic products leading to 5-FU related toxicity syndrome.
      The most common toxicities include myelosuppression, stomatitis, neuropathy, and
      diarrhea. The prevalence of this autosommal codominently inherited
      pharmacogenetic syndrome is approximately 3-5% in the Caucasian population and 8%
      in the African-American population. CASE REPORT: We present here a case of an
      African-American patient with pancreatic cancer who developed a desquamative skin
      rash on the face, trunk, and forearms as the worst rash (grade 3) following 5-FU
      bolus that led to the investigation of DPD enzyme. Measurement of DPD activity by
      radioisotopic assay methods described previously revealed an abnormally low level
      of 0.087 nmol/min/mg protein (reference range: 0.182-0.688 nmol/min/mg protein).
      She was treated toxicity with intravenous steroids and antihistamine therapy.
      Further 5-FU therapy was discontinued. CONCLUSIONS: This case suggest that the
      pattern of toxicities associated with 5-FU can vary, especially in patients with
      different ethnic backgrounds (whites versus non-whites). These findings become of
      further importance as our recent study suggests that DPD deficiency may be more
      common among African-Americans.

PMID- 18326936
TI  - Lymphoepithelial cyst of pancreas. Role of endoscopic ultrasound guided fine
      needle aspiration.
AB  - Lymphoepithelial cysts of the pancreas are extremely rare, benign, nonneoplastic
      cysts that may simulate pseudocysts or cystic neoplasm of the pancreas.
      Endosonographic and cytologic features of pancreatic lymphoepithelial cysts are
      poorly characterized because of their rarity. However, appropriate prospective
      diagnosis of pancreatic lymphoepithelial cysts using endoscopic ultrasound-guided
      fined needle aspiration (EUS-FNA) cytology may permit conservative management
      because of their benign nature. We conducted a MEDLINE search using the MeSH
      terms "pancreas", "cyst" and identified 16 patients who were diagnosed with
      endosonography or computerized tomography (CT) guided fine needle aspiration.
      Usefulness and pitfalls of EUS- or CT-guided cyst fluid analysis in the pre
      operative diagnosis of pancreatic lymphoepithelial cysts are discussed.

PMID- 18326937
TI  - Transversal descriptive study of xenobiotic exposures in patients with chronic
      pancreatitis and pancreatic cancer.

PMID- 18326938
TI  - Indications for surgery in severe acute pancreatitis. Could it also be a
      "manometric" question?

PMID- 18326939
TI  - HDACs and HDAC inhibitors in colon cancer.
AB  - The histone deacetylase (HDAC) family of transcriptional co-repressors have
      emerged as important regulators of colon cell maturation and transformation.
      Pharmacological inhibitors of class I and II HDAC activity (HDACi) are potent
      inducers of growth arrest, differentiation and apoptosis of colon cancer cells in
      vitro and in vivo, implicating a role for these HDACs in tumor promotion.
      Consistent with this role, expression of several HDACs are upregulated in colon
      tumors, while downregulation of specific HDACs inhibits growth of colon cancer
      cells in vitro and intestinal tumorigenesis in vivo. This review focuses on the
      function and transcriptional mechanisms by which class I and II HDACs regulate
      colon cell maturation and transformation, and on the mechanisms by which HDACi
      induce growth arrest, differentiation and apoptosis of colon cancer cells. The
      emerging role of the class III HDAC, Sirt1, in colon cancer progression is also
      discussed.

PMID- 18326940
TI  - The PI 3-kinase regulator Vps15 is required for autophagic clearance of protein
      aggregates.
AB  - Autophagy is involved in cellular clearance of aggregate-prone proteins, thereby
      having a cytoprotective function. Studies in yeast have shown that the PI 3
      kinase Vps34 and its regulatory protein kinase Vps15 are important for autophagy,
      but the possible involvement of these proteins in autophagy in a multicellular
      animal has not been addressed genetically. Here, we have created a Drosophila
      deletion mutant of vps15 and studied its role in autophagy and aggregate
      clearance. Homozygous Deltavps15 Drosophila died at the early L3 larval stage.
      Using GFP-Atg8a as an autophagic marker, we employed fluorescence microscopy to
      demonstrate that fat bodies of wild type Drosophila larvae accumulated autophagic
      structures upon starvation whereas vps15 fat bodies showed no such response.
      Likewise, electron microscopy revealed starvation-induced autophagy in gut cells
      from wild type but not Deltavps15 larvae. Fluorescence microscopy showed that
      Deltavps15 mutant tissues accumulated profiles that were positive for ubiquitin
      and Ref(2)P, the Drosophila homolog of the sequestosome marker SQSTM1/p62.
      Biochemical fractionation and Western blotting showed that these structures were
      partially detergent insoluble, and immuno-electron microscopy further
      demonstrated the presence of Ref(2)P positive membrane free protein aggregates.
      These results provide the first genetic evidence for a function of Vps15 in
      autophagy in multicellular organisms and suggest that the Vps15-containing PI 3
      kinase complex may play an important role in clearance of protein aggregates.

PMID- 18326942
TI  - The geriatric paradox.

PMID- 18326941
TI  - Tumor suppression by autophagy through the management of metabolic stress.
AB  - Autophagy plays a critical protective role maintaining energy homeostasis and
      protein and organelle quality control. These functions are particularly important
      in times of metabolic stress and in cells with high energy demand such as cancer
      cells. In emerging cancer cells, autophagy defect may cause failure of energy
      homeostasis and protein and organelle quality control, leading to the
      accumulation of cellular damage in metabolic stress. Some manifestations of this
      damage, such as activation of the DNA damage response and generation of genome
      instability may promote tumor initiation and drive cell-autonomous tumor
      progression. In addition, in solid tumors, autophagy localizes to regions that
      are metabolically stressed. Defects in autophagy impair the survival of tumor
      cells in these areas, which is associated with increased cell death and
      inflammation. The cytokine response from inflammation may promote tumor growth
      and accelerate cell non-autonomous tumor progression. The overreaching theme is
      that autophagy protects cells from damage accumulation under conditions of
      metabolic stress allowing efficient tolerance and recovery from stress, and that
      this is a critical and novel tumor suppression mechanism. The challenge now is to
      define the precise aspects of autophagy, including energy homeostasis and protein
      and organelle turnover, that are required for the proper management of metabolic
      stress that suppress tumorigenesis. Furthermore, we need to be able to identify
      human tumors with deficient autophagy, and to develop rational cancer therapies
      that take advantage of the altered metabolic state and stress responses inherent
      to this autophagy defect.

PMID- 18326943
TI  - Management of syncope in older adults may require thorough evaluation: a
      conversation with Dr. Mathew Maurer.

PMID- 18326944
TI  - Hypokalemia.

PMID- 18326945
TI  - Priorities in polyvascular disease.

PMID- 18326946
TI  - Statins and heart failure.

PMID- 18326947
TI  - Surrogate decision making.

PMID- 18326948
TI  - Efficacy and safety of intensive statin therapy in the elderly.
AB  - Numerous epidemiologic and intervention trials, including many studying elderly
      cohorts, have demonstrated the importance of lipids in primary and secondary
      preventions of cardiovascular diseases, including coronary heart disease (CHD)
      and stroke. More recent studies have demonstrated that more intensive statin
      therapy that reduces low-density lipoprotein cholesterol levels to <70 to 80
      mg/dL have resulted in more marked cardiovascular event reduction than less
      intensive statin treatment. The authors review the efficacy and safety of
      intensive vs less intensive statin therapy. Specifically, 4 such studies with
      sufficient data in elderly patients, including 2 trials of patients with stable
      CHD and 2 with acute coronary syndrome, demonstrating the efficacy and safety of
      intensive statin therapy with high-dose (80 mg) atorvastatin are reviewed in
      detail. Although elderly patients may be more susceptible to drug interactions
      when receiving high doses of statins, the present evidence supports the use of
      intensive statin therapy in most high-risk elderly patients both with stable CHD
      and following acute coronary syndrome.

PMID- 18326949
TI  - Monotherapy vs combination therapy for dyslipidemia in the elderly.
AB  - Dyslipidemia conveys a major increased risk of future cardiovascular events in
      older persons. Data from large randomized controlled trials confirm that statin
      therapy is as beneficial in older adults as it is in younger persons in both
      primary and secondary prevention. National guidelines support the use of statin
      therapy to reduce low-density lipoprotein cholesterol in older adults, with the
      recommended goal of <100 mg/dL in high-risk patients and an optional goal of <70
      mg/dL in very high-risk patients. In the majority of high-risk older patients,
      these levels of low-density lipoprotein cholesterol can be achieved with initial
      low doses of an efficacious statin, but in some clinical situations, combination
      therapy may be considered. Moreover, statins appear to be safe and well tolerated
      in older age groups. Because of heightened risks of drug-drug interactions, the
      likelihood of polypharmacy in seniors, and issues of tolerability and
      convenience, monotherapy with low doses of an efficacious statin may be
      preferable to combination therapy in elderly individuals.

PMID- 18326950
TI  - Left atrial myxoma in the elderly.

PMID- 18326951
TI  - Frailty, inflammation, and cardiovascular disease: evidence of a connection.
AB  - Frailty is a progressive physiologic decline in multiple body systems marked by
      loss of function, loss of physiologic reserve, and increased vulnerability to
      disease and death. Until recently, frailty has been poorly defined in the medical
      literature. One currently accepted definition of frailty is having 3 of the
      following 5 attributes: unintentional weight loss, muscle weakness, slow walking
      speed, easy exhaustion, and low physical activity. The mechanisms that underline
      frailty remain unclear. Significantly higher levels of markers of inflammation
      and the clotting cascade have been found in frail persons compared with nonfrail
      persons. These markers are also risk factors for the development of coronary
      heart disease. Recent research has indicated that frailty is a clinical
      manifestation of cardiovascular disease, especially of heart failure. Thus,
      understanding the connection between frailty and cardiovascular disease may lead
      to development of new interventions that will prevent and reverse the associated
      morbidity and mortality.

PMID- 18326952
TI  - Sinus venosus atrial septal defect diagnosed at age 82.

PMID- 18326953
TI  - Coronary events in persons aged 75 years or older in Finland from 1995 to 2002:
      the FINAMI study.
AB  - The authors used population-based myocardial infarction (MI) register data to
      examine trends in incidence, case fatality, treatment strategies of MI, and
      coronary heart disease (CHD) mortality in persons aged 75 to 99 years in 4 areas
      of Finland during 1995 through 2002. This age group contributed 53% (n=13,977) of
      all CHD events, and 65% occurred in women. CHD mortality declined among men
      annually by 3.5% and 1.0% in the 75- to 84-year-old and 85- to 99-year-old age
      groups, respectively. Among women, it declined by 2.2% per year in the 75- to 84
      year-old age group but increased by 1.3% per year in the 85- to 99-year-old age
      group. MI attack rate did not change in men but increased significantly in women
      aged 85 to 99 years. Clinical management of MI in elderly patients was more
      conservative than in middle-aged patients. In conclusion, one-half of all CHD
      events occur among persons aged 75 years or older, and elderly patients with CHD
      represent an increasing burden to the health care system.

PMID- 18326954
TI  - Electrocardiographic intervals in the healthy geriatric population--what are the
      "normals"?
AB  - The authors compared the average electrocardiographic (ECG) intervals in a
      population of patients 80 years and older with published "normal" values. The
      medical records of patients who presented to the Mayo Clinic for health
      maintenance examinations and who had a routine ECG performed (N=702) were
      selected. Age; sex; rhythm; PR, QRS, and QTc intervals; incidence of cardiac
      disease; and presence of interval-prolonging medication were recorded. Reference
      ranges were estimated from the data and compared with standard cutoffs for
      prolonged intervals. Interval values were significantly higher in men. Reference
      ranges were established separately for both sexes based on the subset of 578
      patients without a history of cardiac disease and not taking interval-prolonging
      medication. In all instances, the ranges were higher than the recommended
      cutoffs. The upper limits for prolonged PR, QRS, and QTc intervals were found to
      be significantly higher in a population of patients older than 80 years.

PMID- 18326955
TI  - Biomarkers, age, and coronary artery remodeling in patients with acute coronary
      syndrome.
AB  - To investigate the relationship between age and coronary artery remodeling in
      patients with acute coronary syndrome (ACS), 56 patients with ACS were identified
      by intravascular ultrasound (IVUS). Remodeling index (RI) (37 cases of RI > or =1
      vs 19 cases of RI <1) and dimidiate age groups (27 patients younger than 60 years
      vs 29 patients 60 years or older) were compared, and the relationships among
      biomarkers, age, and arterial remodeling were analyzed. There was a significant
      difference in age between positive and negative remodeling groups (55+/-13 vs
      62+/-10 years; P=.038); RI and triglyceride level showed a statistical
      correlation (r=0.32; P=.02) and a significant inverse correlation between age and
      RI (r=-0.47; P<.001). The multivariable linear regression analysis demonstrated
      that age was an independent predictor of RI (Bate -0.37; 95% confidence interval,
      0.93-1.08; P=.04). Age may be an important factor of arterial remodeling. Low
      density lipoprotein or triglyceride level may be associated with attenuated
      coronary vascular remodeling with aging.

PMID- 18326956
TI  - Systolic anterior motion of a retained anterior mitral valve leaflet following
      mitral valve replacement.

PMID- 18326957
TI  - Stagnation and the critical need for hypertension subtyping.

PMID- 18326958
TI  - Efficacy of the combination of amlodipine and valsartan in patients with
      hypertension uncontrolled with previous monotherapy: the Exforge in Failure after
      Single Therapy (EX-FAST) study.
AB  - In this randomized, double-blind, multicenter study, patients whose blood
      pressure (BP) was uncontrolled by monotherapy were switched directly to
      amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP
      control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in
      72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving
      amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving
      amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean
      sitting systolic and diastolic BP were significantly greater with the higher dose
      (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg;
      P=.0046). Incremental BP reductions were also achieved with both regimens
      irrespective of previous monotherapy, hypertension severity, diabetic status,
      body mass index, and age. Peripheral edema was the most frequent adverse event.
      These results provide support for the BP-lowering benefits of complementary
      antihypertensive therapy with amlodipine and valsartan in patients with
      hypertension uncontrolled by previous monotherapy.

PMID- 18326959
TI  - Can ischemic stroke be caused by acute reduction of blood pressure in the acute
      phase of cardiovascular disease?
AB  - Acute-phase cardiovascular disease (CVD) frequently presents with markedly
      elevated blood pressure (BP) levels and often requires fairly rapid lowering of
      BP. On the other hand, aggressive lowering of systemic BP to the point that the
      cerebral BP decreases below a certain threshold may result in ischemic stroke.
      The authors retrospectively studied 192 consecutive patients with CVD who had
      markedly elevated BP and end-organ damage. Ischemic stroke was noted in 12 of
      these patients during BP-lowering therapy. The incidence of ischemic stroke did
      not differ significantly between a standard BP-lowering group, in which the
      target BP reduction was within the parameters of the Seventh Report of the Joint
      National Committee on Prevention, Detection, Evaluation, and Treatment of High
      Blood Pressure guidelines, and a rapid BP-lowering group, in which the target BP
      was below these guidelines (7.1% vs 2.6%, respectively; P=.27, not significant).
      In stepwise multiple regression analysis, diabetes mellitus (beta=0.203, P=.008)
      and acute pulmonary edema (beta=0.228, P=.003) remained significant factors
      associated with the incidence of stroke. Thus, acute pulmonary edema and diabetes
      were the most important factors related to ischemic stroke during BP reduction in
      patients with marked elevations of BP regardless of the rapidity of BP lowering.

PMID- 18326960
TI  - Beneficial effect of angiotensin II type 1 receptor blocker antihypertensive
      treatment on arterial stiffness: the role of smoking.
AB  - The purpose of the present study was to assess angiotensin receptor blocker (ARB)
      treatment on arterial stiffness in select hypertensive patients and define
      possible differences between smokers and nonsmokers. The authors evaluated 81
      consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated
      essential hypertension with high plasma renin activity who were administered
      monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into
      smokers (n=24) and nonsmokers (n=57). Carotid-radial pulse wave velocity (PWVc
      r), carotid-femoral pulse wave velocity (PWVc-f), and augmentation index (AIx)
      were measured before and 6 months after ARB antihypertensive treatment. All mean
      values of elastic effect indices were decreased after irbesartan monotherapy
      (AIx, from 26.3%to 21.2% [P<.01;] PWVc-f, from 7.7 m/s to 7.3 m/s [P<.05], and
      PWVc-r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers,
      no difference was noted in AIx and PWVc-f change (P=not significant), while PWVc
      r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB
      treatment may favorably affect arterial stiffness and wave reflections in
      hypertensive chronic smokers with elevated plasma renin levels.

PMID- 18326961
TI  - Electrocardiographic left ventricular hypertrophy regression induced by an
      angiotensin receptor blocker-based regimen in hypertensive patients with the
      metabolic syndrome: data from the SARA Study.
AB  - The authors assessed the effect of an angiotensin receptor blocker (candesartan)
      based regimen on electrocardiographic left ventricular hypertrophy (ECG-LVH) in
      276 patients with hypertension, including 141 with the metabolic syndrome (MS).
      Baseline blood pressure (BP) and ECG-LVH parameters did not differ in patients
      with and without MS. At the study's end, BP had decreased similarly in both
      groups. At baseline, 26.1% of patients with MS and 24.7% without MS exhibited ECG
      LVH by Cornell product (CorP) criteria (P=NS); 26.8% and 17.2%, respectively, by
      Sokolow-Lyon product (SokP) (P=.01); 11.4%and 11.8% by Cornell voltage (CorV)
      (P=NS); and 12.4% and 6.5% by Sokolow-Lyon voltage (SokV) (P=.01). At the study's
      end, in the MS group, prevalence of ECG-LVH was reduced to 19.5% from 26.1%
      (P=.001), to 8.5% from 11.4% (P=.01), and to 24.4% from 26.8%(P=.03) by CorP,
      CorV, and SokP, respectively. In patients without MS, only the CorP criterion
      showed a significant decrease in ECG-LVH prevalence, declining to 20.5% (P=.01).
      The relative risk reduction of ECG-LVH was higher in patients with MS according
      to CorV and SokP criteria (P<.01).

PMID- 18326962
TI  - Mail education is as effective as in-class education in hypertensive Korean
      patients.
AB  - Many Korean American persons have hypertension, but competing life priorities
      often prevent them from attending health-promotion educational activities. Using
      principles of community-based participatory research, the authors conducted a
      prospective clinical trial to determine the effectiveness of a mailed vs an in
      class culturally tailored education intervention. A total of 380 hypertensive
      Korean American persons from the Baltimore/Washington area were assigned to a
      more intense in-class education group or a less intensive mail education group.
      Evaluation of postintervention blood pressure (BP) outcomes revealed that
      significant reductions in systolic BP (13.3 mm Hg and 16.1 mm Hg, respectively)
      and diastolic BP (9.5 mm Hg and 10.9 mm Hg) and increases in BP control rates
      (42.3% and 54.3%) were achieved in both groups. No significant differences in BP
      outcomes between groups, however, were found. In conclusion, education by mail
      was an effective strategy for improving BP control and may be a viable approach
      for other immigrant groups if the education materials address their cultural
      needs.

PMID- 18326963
TI  - Escalating antihypertensive medications in end-stage renal disease patients does
      not improve blood pressure control.
AB  - The authors examined the efficacy of antihypertensive medication use in end-stage
      renal disease (ESRD). They compared achieved blood pressures (BPs) in a cross
      sectional study of 106 ESRD patients whose medications had not been changed for
      at least 2 months. Group 1 (n=36) included patients who took 0 or 1 medication;
      group 2 (n=56), 2 or 3 medications; and group 3 (n=14), > or =4 medications. The
      population's mean age was 55.1 years, 87% were African American, and 57% were men
      weighing 76.9 kg who were on 229 minutes of hemodialysis with an edKt/V of 1.35;
      there was no difference between the 3 groups. The authors found a difference in
      the mean BPs: 139/72 mm Hg in group 1, 154/82 mm Hg in group 2, and 165/91 mm Hg
      in group 3 (P=.01 for systolic, P=.002 for diastolic), with a mean arterial
      pressure difference of 94.4, 106.4, and 115.4 mm Hg (P=.002). The authors
      conclude that in this group of primarily African American patients, the control
      of hypertension in ESRD is not achieved by escalating the number of
      antihypertensive medications.

PMID- 18326964
TI  - Prevention of cardiovascular events by treating hypertension in older adults: an
      evidence-based approach.
AB  - Hypertension in older adults is not well controlled in clinical practice.
      Isolated systolic hypertension is often more difficult to manage. A systematic
      PubMed search was conducted to look for evidence showing benefits of lowering
      blood pressure (BP) in older hypertensive adults. Lowering BP in these
      individuals significantly reduces the risk of coronary artery disease, stroke,
      and cardiovascular and all-cause mortality. Based on trial evidence, a low-dose
      diuretic should be considered the most appropriate first-step treatment for
      preventing cardiovascular morbidity and mortality. Therapy with >1 medication is
      often necessary to reduce BP in these patients. There is unequivocal evidence
      that cardiovascular events can be prevented in older adults, even those older
      than 80 years, by treating hypertension.

PMID- 18326965
TI  - Identifying early cardiovascular disease to target candidates for treatment.
AB  - Most attempts to identify individuals at risk for cardiovascular morbid events
      have involved screening for risk factors. These traditional risk factors do not
      identify the underlying atherosclerotic disease nor assess the severity of
      disease in individual patients. The goal for identifying a marker or markers for
      early cardiovascular disease that could serve as a surrogate for disease
      progression and ultimate morbid events is to improve the precision for early
      detection and treatment. The authors utilize a variety of techniques, which
      consist of 7 vascular tests (large and small artery elasticity, resting blood
      pressure and exercise blood pressure response, optic fundus photography, carotid
      intimal-media thickness, and microalbuminuria) and 3 cardiac tests
      (electrocardiography, [N-terminal pro-] B-type natriuretic peptide, and left
      ventricular ultrasonography). Each test is individually scored, and the total
      disease score is the sum of all the test scores. A study is ongoing to compare
      the new disease score vs the classical Framingham risk estimate in the prediction
      of cardiovascular events.

PMID- 18326966
TI  - Are more tests needed?

PMID- 18326967
TI  - Beta-blockers in the treatment of hypertension: new data, new directions.

PMID- 18326968
TI  - Mechanisms and treatment of resistant hypertension.
AB  - Resistant hypertension is defined as blood pressure (BP) that remains
      uncontrolled in spite of the use of >/=3 antihypertensive medications. Stricter
      BP goals, higher obesity rates, older age, and increased use of exogenous BP
      elevating substances are related to an increasing prevalence of resistant
      hypertension. The evaluation of patients with resistant hypertension is focused
      on identifying contributing and secondary causes of hypertension, including
      hyperaldosteronism, obstructive sleep apnea, chronic kidney disease, renal artery
      stenosis, and pheochromocytoma. Hyperaldosteronism is now recognized as the most
      common cause of resistant hypertension, and all patients with resistant
      hypertension should be screened with a plasma aldosterone/renin ratio even if the
      serum potassium level is normal. Treatment includes removal of contributing
      factors, appropriate management of secondary causes, and use of effective
      multidrug regimens. Recent studies indicate that the addition of spironolactone
      to standard treatment induces significant BP reduction in most patients with
      resistant hypertension.

PMID- 18326969
TI  - The Food and Drug Administration and over-the-counter statins: an opportunity
      lost?

PMID- 18326970
TI  - Bayesian meta-analysis of tissue angiotensin-converting enzyme inhibitors for
      reduction of adverse cardiovascular events in patients with diabetes mellitus and
      preserved left ventricular function.
AB  - The role of angiotensin-converting enzyme (ACE) inhibitors in diabetic patients
      with preserved ventricular function is uncertain. Tissue ACE inhibitors have been
      defined by increased lipophilicity and structural characteristics that result in
      greater tissue-specific ACE binding when compared with plasma ACE inhibitors. A
      Bayesian meta-analysis of randomized trials was conducted to evaluate tissue ACE
      inhibitors in prevention of cardiovascular disease among patients with diabetes
      mellitus and preserved left ventricular function. Four trials were selected that
      evaluated 2 different ACE inhibitors and included 10,328 patients (43,517 patient
      years). The Perindopril Substudy in Coronary Artery Disease and Diabetes
      (PERSUADE) and the Perindopril Protection Against Recurrent Stroke Study
      (PROGRESS) compared the effects of perindopril vs a placebo, and the Heart
      Outcomes Prevention Evaluation (HOPE) and the Non-Insulin-Dependent Diabetes,
      Hypertension, Microalbuminuria, Proteinuria, Cardiovascular Events, and Ramipril
      (DIABHYCAR) study investigated the impact of ramipril vs a placebo. Bayesian meta
      analysis of sequential trials and sensitivity analysis of therapeutic response
      were subsequently computed. Bayesian meta-analysis determined reduced risk of
      cardiovascular mortality (PB=.991), myocardial infarction (PB=.999), and the need
      for invasive coronary revascularization (PB=.995) when compared with placebo.
      Total mortality was also decreased (PB=.967), while the risk of stroke (PB=.907)
      and hospitalization for heart failure (PB=.923) were impacted. Bayesian meta
      analysis of randomized trials suggests that tissue ACE inhibitors decrease the
      probability that diabetic patients with preserved left ventricular function will
      experience myocardial infarctions and cardiovascular death and reduce overall
      mortality.

PMID- 18326971
TI  - The endocannabinoid system: a promising novel mechanistic pathway in the
      cardiometabolic syndrome.
AB  - The endocannabinoid system (ECS) is a neuroendocrine system that modulates
      several cardiometabolic processes. An overactive ECS is implicated as a
      significant contributor to the cardiometabolic syndrome and obesity, in addition
      to a large number of other physiologic processes. Endocannabinoid receptors have
      been detected centrally and peripherally, regulating appetite, food intake,
      metabolism, and storage. ECS blockade is thought to be a promising new
      pharmacologic modality of improving the unfavorable metabolic risk profile in
      patients with the cardiometabolic syndrome and obesity.

PMID- 18326972
TI  - Reversal of diuretic-associated impaired glucose tolerance and new-onset
      diabetes: results of the STAR-LET study.
AB  - Reversal of new-onset diabetes secondary to thiazide diuretic use remains
      questionable. STAR-LET was a 6-month extension of the Study of
      Trandolapril/Verapamil SR and Insulin Resistance (STAR), which assessed the
      effects of a fixed-dose renin-angiotensin system inhibitor
      (RASI)/hydrochlorothiazide (HCTZ) combination on changes in 2-hour oral glucose
      tolerance test (OGTT) results. STAR-LET explored whether the glycemic impact of
      HCTZ could be reversed by conversion to a RASI/verapamil combination. The primary
      outcome was change in 2-hour OGTT results. Fifty-one percent of the STAR patients
      were enrolled in STAR-LET. The 2-hour OGTT value (mmol/L) was unchanged from STAR
      baseline in the RASI/verapamil group (7.7+/-2.4 vs 8.1+/-3.3; P=.18) and improved
      in those who were switched from RASI/HCTZ to RASI/verapamil (8.5+/-3.0 vs 7.2+/
      2.3; P<.001). This exploratory study suggests that the impairment in glycemic
      control seen with use of a thiazide diuretic combined with a RASI can be reversed
      by switching to a regimen that does not include a diuretic.

PMID- 18326973
TI  - The cardiometabolic syndrome and liver disease.

PMID- 18326974
TI  - Ethnic gap in coronary artery disease: comparison of the extent, severity, and
      risk factors in Arab and Jewish middle-aged women.
AB  - The authors examined risk factors and extent of coronary artery disease (CAD)
      among Jewish and Arab women in Jerusalem, where Arab women were found to have
      worse outcome. All angiographically confirmed cases of CAD among women aged 45 to
      65 years who were hospitalized during 1990 to 1995 consisted of 40 Arab and 179
      Jewish patients. Arab women had more atypical clinical presentations (P<.0001)
      and more extensive CAD (P=.0016) despite younger age (53+/-3 vs 55+/-5 years;
      P<.0003) and lesser smoking (P<.0006). The Arab women, however, were more likely
      to be obese (80% vs 46%; P=.0002), be physically inactive (100% vs 89%; P=.0285),
      and have diabetes mellitus (73% vs 40%; P=.0004). Moreover, they were more likely
      to have 3 or more risk factors (45% vs 23%; P=.036). Thus, a combination of an
      atypical presentation and higher risk (ie, diabetes mellitus combined with
      hypertension and other risk factors) and much more extensive disease readily
      explains their worse outcome.

PMID- 18326975
TI  - Calciphylaxis: a severe complication of the cardiometabolic syndrome in patients
      receiving hemodialysis.

PMID- 18326976
TI  - The apolipoprotein b/apolipoprotein AI ratio in the metabolic syndrome-should we
      start using it?

PMID- 18326977
TI  - Calciphylaxis and the cardiometabolic syndrome: the emerging role of sodium
      thiosulfate as a novel treatment option.

PMID- 18326978
TI  - Vascular compliance in the cardiometabolic syndrome.
AB  - Elevated systolic blood pressure and increased pulse pressure are important
      predictors of vascular stiffening (compliance), left ventricular hypertrophy,
      coronary heart disease, heart failure, stroke, vascular dementia, and chronic
      kidney disease. Advances in noninvasive methods that measure arterial stiffness
      have led to increased understanding of the mechanisms underlying vascular
      dysfunction and the development of associated risk factors. The ability to detect
      and monitor changes in the physical properties of arteries has the potential to
      allow early interventions that may prevent disease or attenuate its progression.
      In this paper, the authors briefly review the various methods available to
      measure vascular compliance and review pathologic processes that lead to insulin
      resistance, endothelial dysfunction, inflammation, and sympathetic activation,
      all of which may contribute to increased arterial stiffness in the
      cardiometabolic syndrome. Strategies to improve vascular compliance are also
      discussed.

PMID- 18326979
TI  - The metabolic syndrome adds incremental value to the Framingham risk score in
      identifying asymptomatic individuals with higher degrees of inflammation.
AB  - Recent studies have shown that elevated white blood cell (WBC) counts
      independently predict adverse cardiovascular disease (CVD) outcomes. The
      metabolic syndrome (MS) is known to be associated with a higher degree of
      inflammation and increased CVD risk. It is unclear, however, whether MS provides
      incremental information to the Framingham risk score (FRS). The authors studied
      458 asymptomatic men, of whom 112 had MS. WBC count was used as a marker of
      inflammation. The odds ratio (OR) for presence of WBCs in the highest quartile vs
      the lower 3 quartiles was 2.2; 95% confidence interval (CI), 1.39-3.40 for MS.
      After further adjustment for the FRS, the relationship remained significant (OR,
      1.97; 95% CI, 1.25-3.13). The ability to identify higher levels of WBCs with MS
      was especially important in the low-risk men (OR, 2.66; 95% CI, 1.39-5.07). The
      study findings suggest that MS adds value to the FRS in identifying those with
      higher degrees of inflammation, especially among those classified as low-risk by
      the FRS.

PMID- 18326980
TI  - Effects of angiotensin-converting enzyme inhibitor therapy on levels of
      inflammatory markers in response to exercise-induced stress: studies in the
      metabolic syndrome.
AB  - The authors sought to determine whether the angiotensin-converting enzyme (ACE)
      inhibitor perindopril has beneficial effects on vascular markers of inflammation
      in patients with the metabolic syndrome when exposed to exercise-induced stress.
      Thirty patients with the metabolic syndrome were randomized to perindopril (4
      mg/d) or placebo in a double-blind fashion for 4 weeks. Prior to treatment, the
      patients underwent an exercise treadmill study to a level of 8 metabolic
      equivalents. Circulating monocyte CD11b expression, levels of soluble interleukin
      6 (sIL-6), and levels of vascular cell adhesion molecule-1 (VCAM-1) were
      measured. After the treatment period, exercise treadmill study and measurement of
      markers were repeated. Treatment with perindopril reduced sIL-6 levels at pre
      exercise by 22% and at 1 and 30 minutes by 30% and 33%, respectively (P<.005).
      Levels of soluble VCAM-1 in perindopril-treated patients were reduced at pre
      exercise by 25% and at 1 and 30 minutes by 31% and 37%, respectively. Treatment
      with perindopril reduced monocyte CD11b expression by 25%. In response to
      exercise-induced physical stress, the addition of an ACE inhibitor differentially
      regulates markers of inflammation, thereby providing potential vascular
      protection in the metabolic syndrome.

PMID- 18326981
TI  - High-dose atorvastatin after stroke or transient ischemic attack: The Stroke
      Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators.

PMID- 18326982
TI  - Homocysteine competes for the peroxisome proliferator-activated receptor nuclear
      receptors.

PMID- 18326983
TI  - Environmental stress, erythrocyte dysfunctions, inflammation, and the metabolic
      syndrome: adaptations to CO2 increases?
AB  - In the Western world, the prevalence of the metabolic syndrome is increasing
      exponentially. Chronic subacute inflammation characterizes the syndrome,
      suggesting that inflammation might be a common denominator that links obesity to
      its pathologic sequelae. Potential mechanisms for the activation of inflammation
      include current air pollution inhalation and/or excess food intake. Both of these
      environmental factors have, in fact, been shown to promote oxidation followed by
      the release of proinflammatory cytokines. Potential sources of systemic
      inflammation include oxidized erythrocytes. Increased exogenous or endogenous CO2
      deoxygenates hemoglobin, thereby increasing the fraction of hemoglobin reacting
      with nitrite to form methemoglobin together with release of superoxide and nitric
      oxide. These may form peroxynitrite, which may oxidize erythrocytes. Macrophages
      may then recognize and engulf these cells, thereby releasing proinflammatory
      cytokines. Therefore, studies should focus on the red blood cell and its proteins
      to finely target and appropriately treat a world pandemic ominously related to
      CO2 increases.

PMID- 18326984
TI  - Noninvasive diagnosis of subclinical atherosclerosis in cardiometabolic syndrome:
      a call to action.

PMID- 18326985
TI  - The family history as a tool to identify patients at risk for dilated
      cardiomyopathy.

PMID- 18326986
TI  - Sleep-disordered breathing, cognitive functioning, and adherence in heart
      failure: linked through pathology?
AB  - Heart failure (HF) is well recognized as a condition resulting from chronic
      neurohormonal activation. Sleep-disordered breathing (SDB) as a neurohormonal
      disorder is less recognized. In SDB, whether obstructive or central in nature,
      nightly repetitive cycles of hypoxia-reoxygenation produce intense sympathetic
      activation and deprive the body of much needed sleep. Both HF and SDB are
      associated with fatigue, cognitive impairment, and challenges for adherence to
      prescribed therapies. Together, the combination of HF and SDB can have
      particularly ominous consequences for cognitive functioning, decision making,
      adherence and, ultimately, outcomes. The suboptimal adherence seen in patients
      with both HF and SDB may result from a neurohormonal synergism that exists
      between the 2 conditions.

PMID- 18326987
TI  - Cardiovascular nursing in Switzerland-a developing field.

PMID- 18326988
TI  - Sex differences in prodromal symptoms of patients with acute coronary syndrome: a
      pilot study.
AB  - Increasing evidence suggests that there are sex/gender differences in the
      presentation and prodromal symptoms of acute coronary syndrome (ACS). The purpose
      of this pilot study was to identify sex differences in the prodromal symptoms of
      ACS using the McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey
      (MAPMISS). Telephone surveys using the MAPMISS were conducted between 4 and 6
      months after the ACS event. Seventy-six patients (24 women) participated in the
      study. The women generally reported higher prodromal scores. Moreover, scores
      demonstrated differences in prodromal symptoms based on menopausal status. The
      premenopausal and perimenopausal women reported a greater number and higher
      frequency of symptoms compared with the men and menopausal women. The results of
      this study suggest that both men and women report nontraditional prodromal
      symptoms of ACS. In addition, there appears to be a difference in the frequency
      and number of symptoms reported based on menopausal status.

PMID- 18326989
TI  - Chart it like you see it.

PMID- 18326990
TI  - Telemonitoring of heart failure patients and their caregivers: a pilot randomized
      controlled trial.
AB  - Heart failure (HF) is the leading cause of rehospitalization in older adults. The
      purpose of this pilot study was to examine whether telemonitoring by an advanced
      practice nurse reduced subsequent hospital readmissions, emergency department
      visits, costs, and risk of hospital readmission for patients with HF. One hundred
      two patient/caregiver dyads were randomized into 2 groups postdischarge; 84 dyads
      completed the study. Hospital readmissions, emergency department visits, costs,
      and days to readmission were abstracted from medical records. Participants were
      interviewed soon after discharge and 3 months later about effects of
      telemonitoring on depressive symptoms, quality of life, and caregiver mastery.
      There were no significant differences due to telemonitoring for any outcomes.
      Caregiver mastery, informal social support, and electronic home monitoring were
      not significant predictors for risk of hospital readmission. Further studies
      should address the interaction between the advanced practice nurse and follow-up
      intervention with telemonitoring of patients with HF to better target those who
      are most likely to benefit.

PMID- 18326991
TI  - ACC/AHA non-ST elevation myocardial infarction guidelines' revision 2007:
      implications for nursing practice.

PMID- 18326992
TI  - Correlates of fatigue in patients with heart failure.
AB  - This study was conducted to determine the prevalence of fatigue and identify its
      demographic, clinical, and psychological correlates in 150 heart failure (HF)
      patients (73% men, 66% Caucasian, mean age 55.0 years, mean ejection fraction
      26.7%+/-11%), from a single HF center, using the Profile of Mood States-Fatigue
      Subscale, the Minnesota Living With Heart Failure Questionnaire, and the Beck
      Depression Inventory. Sociodemographic and clinical data were obtained through
      self-report and chart abstraction. High levels of fatigue were reported in 50.4%
      of men and 51.2% of women. In a multivariate model, maximal workload, physical
      health, emotional health, and depression explained 51% of the variance in fatigue
      (P<.001). Fatigue in patients with HF is associated with both clinical and
      psychosocial variables, offering a number of targets for intervention. These
      findings suggest the need for multiple risk factor intervention strategies that
      improve physical and emotional health to decrease fatigue. Patients with
      depression warrant particular scrutiny.

PMID- 18326993
TI  - Rapid response saves lives.

PMID- 18326994
TI  - Relationship of heart failure patients' knowledge, perceived barriers, and
      attitudes regarding low-sodium diet recommendations to adherence.
AB  - The purposes of this study were to describe heart failure patient perceptions
      regarding instructions received for following a low-sodium diet and the benefits,
      barriers, and ease and frequency of following the diet. A total of 246 patients
      with heart failure referred from academic medical centers in the United States
      and Australia participated in the study. A subset of 145 patients provided 24
      hour urine samples for sodium excretion assessment. While most (80%) patients
      reported receiving recommendations to follow a low-sodium diet, their recall of
      specific instructions was poor. Although the majority (75%) reported following a
      low-sodium diet most or all of the time, 24-hour urine sodium excretion indicated
      that only 25% of patients were adherent. Patients who reported being more
      adherent, however, had lower urine sodium excretion levels. Attitudes regarding
      difficulty in and perceived benefits of following the diet were not related to
      sodium excretion. Data on attitudes and barriers provided guidance for strategies
      to improve adherence.

PMID- 18326995
TI  - Self-management of atrial fibrillation: a new frontier for nursing research.

PMID- 18326996
TI  - Sleep and health.

PMID- 18326997
TI  - Aspirin revisited: helpful or harmful? What is the correct dose for a certain
      population?

PMID- 18326998
TI  - Diagnosis and management of primary cicatricial alopecia: part II.
AB  - The second part of this 2-part article reviews clinical features, histology,
      management, and treatment of neutrophilic primary cicatricial alopecias
      (folliculitis decalvans and dissecting folliculitis) and mixed primary
      cicatricial alopecias (acne keloidalis, acne necrotica, and erosive pustular
      dermatosis).

PMID- 18326999
TI  - Lamisil (terbinafine) oral granules.

PMID- 18327000
TI  - Genital human papilloma virus infection: advances in prevention for the long-term
      good of all.
AB  - The wonderful thing about being a physician, even an ordinary dogsbody of one, is
      that we live in a world in which almost every week scientists, researchers, and
      clinicians taking part in well-conducted trials usually backed by private capital
      and the pharmaceutical industry manage to perfect advances that will ultimately
      benefit not just our patients but the families and society in which our patients
      live. That is, of course, if we bother, even in the usual way of busy
      practitioners, skimming through medical journals or glancing at progress from Web
      sources. Most of us do not do so as well as we would like, but merely by reading
      this article, education somehow touches us. (Damn, there goes an interruption; we
      have just been jolted out of our thoughts!).

PMID- 18327001
TI  - Molluscum contagiosum.

PMID- 18327002
TI  - Great dermatology libraries: the Max and Margareta Wolf Dermatology Library.

PMID- 18327003
TI  - Tacrolimus: approved and unapproved dermatologic indications/uses-physician's
      sequential literature survey: part II.
AB  - Tacrolimus has been a useful therapeutic tool in dermatology practice ever since
      its inception. Accordingly, many "off-label" applications have been reported.
      Thus, its local immunosuppressive and steroid-sparing action stands recognized.
      Hence, its indications/uses were extended beyond atopic dermatitis to cover
      several dermatoses including other types of eczema, papulosquamous disorder of
      cornification, rosacea, other inflammatory skin conditions, vesicobullous
      disease, connective tissue disease, graft versus host disease, and follicular
      disorders. Many such diseases found to respond to tacrolimus therapy have been
      briefly recounted. It is worthwhile to conceive, however, that this topical
      immunomodulator should be reserved for use only as an alternative, should the
      conventional treatment be unresponsive. Hence, guarded use is warranted.

PMID- 18327004
TI  - Coexistent psoriasis and bullous pemphigoid responding to mycophenolate mofetil
      monotherapy.
AB  - A 73-year-old woman with a 50-year history of psoriasis was referred to our
      clinic with a 4-month duration of tense bullae on erythematous base and erosions
      localized on her lower extremities and torso (Figure 1A). Neither the oral nor
      the ocular mucosa had been involved. The lesions were intensively pruritic,
      significantly affecting the quality of her life. At the time of the examination,
      the patient presented with psoriatic plaques with adherent scales confined on the
      scalp (Figure 2A). According to the patient's history, her limited psoriasis was
      partially controlled with occasional topical medications (topical
      corticosteroids, calcipotriol, and tar shampoo). She also had insulin-dependent
      diabetes mellitus, asthmatic bronchitis, and partially controlled hypertension
      with hyperlipidemia. A biopsy specimen was taken from lesional skin on her feet,
      and a histological examination showed a subepidermal blister with an inflammatory
      cell infiltrate in the upper dermis. No drugs were incriminated, and diagnosis of
      bullous pemphigoid was confirmed by Western immunoblotting of serum. Laboratory
      investigation revealed mild thrombocytopenia of 110,000/mm(3), cholesterol 279
      mg/dL, and triglycerides 210 mg/dL. The patient could not tolerate prednisolone
      and cyclosporine because of hypertension and diabetes, or azathioprine because of
      the mild thrombocytopenia; she did not consent to receiving biologics.
      Mycophenolate mofetil (MMF) was then considered a choice. The patient agreed, and
      she was initially administered 1000 mg/d. After 2 weeks, the dosage increased to
      1000 mg twice a day because of the formation of new blisters. Within 8 weeks of
      treatment with MMF 2000 mg/d, marked improvement was observed and her pruritus
      resolved. Complete remission of bullous pemphigoid and psoriasis was achieved
      within 3 and 4 months, respectively. Routine laboratory studies were performed
      before treatment and every month during therapy, and MMF was tolerated without
      side effects. The treatment was continued for 6 months with no subsequent relapse
      of the dermatoses (Figure 1B and Figure 2B).

PMID- 18327005
TI  - Acne in adult women.

PMID- 18327006
TI  - Photo capsules.

PMID- 18327007
TI  - Erdheim-Chester disease with cutaneous features in an Indian patient.
AB  - A 60-year-old Indian woman presented with multiple asymptomatic, firm swellings
      over the face that had been progressively increasing for the past 3.5 years. She
      complained of dry cough and dyspnea of 2 years' duration, which was diagnosed as
      interstitial lung disease (ILD) based on chest radiography and high-resolution
      computed tomography. Apart from occasional backaches, the patient had no other
      systemic complaints. The results of the general physical examination was normal,
      with no lymphadenopathy. Cutaneous examination revealed multiple (5) firm,
      yellowish to skin-colored well-defined nodules with irregular margins ranging in
      size from 1 x 1 cm to 4 x 8 cm present over the left periorbital region and right
      jawline, with overlying telangiectasias on the skin (Figure 1). On examination of
      the chest, she had generalized rhonchi and crepts; the remainder of the systemic
      examination results were normal. Fine needle aspiration cytology from the nodule
      in the periorbital area revealed a dispersed population of spindle cells,
      numerous foam cells, and giant cells suggestive of xanthogranuloma.
      Histopathology from the nodule on the jawline showed abundant foamy histiocytes
      in the dermis with few multinucleated giant cells and lymphocytes (Figure 2). The
      foamy histiocytes were periodic acid-Schiff-positive. On immunohistochemistry,
      histiocytes were CD68-positive. Findings of routine investigations including
      hemogram, peripheral blood smear, and blood chemistry were normal. Radiography of
      the lumbosacral spine showed mixed osteolytic and osteosclerotic lesions
      involving L5-S1, the left sacroiliac joint, and the left iliac blade. Findings
      from radiography of the long bones and skull were normal. Contrast-enhanced
      computed tomographic scan of the abdomen and pelvis showed areas of osteolysis,
      with marginal sclerosis present bilaterally that involved the iliac blades and
      the right half of the sacrum. A methylene diphosphate bone scan revealed
      increased tracer uptake seen at the fifth lumbar vertebrae, bilateral sacroiliac
      bone, and left iliac bone and areas of photopenia in sacrum. Bone marrow
      aspiration from the sternum showed normal cells with a normal erythroid-to
      myeloid ratio. Ultrasonographic B scanning of the eyes showed no retro-orbital
      involvement. Erdheim-Chester disease was diagnosed in this patient on the basis
      of diagnostic histopathology, radiologic features involving bones, and ILD and
      treatment with 40 mg oral prednisolone daily was started. Surgical debulking of
      her skin lesions was planned, but the patient refused due to her worsening ILD.

PMID- 18327008
TI  - Ulcus vulvae acutum in a 13-year-old girl after influenza A infection.
AB  - A 13-year-old otherwise healthy premenarchal girl presented with acute onset of
      painful vulvar ulcerations. One day before developing vulvar ulcerations, she
      experienced flu-like symptoms, including a low-grade fever, cough, sore throat,
      and myalgia. Results of a throat swab were positive for influenza A infection
      (polymerase chain reaction [PCR] assay), and the patient was treated with
      oseltamivir. The patient's constitutional symptoms improved slightly, but within
      2 days after her initial presentation, she returned to her primary care provider
      and described 24 hours of dysuria and vulvar swelling. She had a history of
      herpes labialis (cold sores) and rare episodes of minor oral aphthae (canker
      sores) that occurred less than twice a year. The patient denied a history of
      sexual activity, sexual abuse, or physical trauma. Physical examination showed
      ulceration and swelling of the labia minora, and the patient received an empiric
      dose of acyclovir (200 mg 4 times daily) for presumed autoinoculated herpes
      simplex virus (HSV) infection. An ulcer swab was performed, and urinalysis
      revealed no evidence of infection. Two days later, the patient presented to the
      emergency department with increasing vulvar pain and vaginal discharge. The
      previous ulcer swab findings were negative for HSV (PCR assay), and consequently,
      acyclovir was discontinued after 1 day of therapy. She received topical viscous
      lidocaine and an empiric dose of oral fluconazole. The lidocaine provided
      temporary symptomatic relief. Results of DNA amplification studies were negative
      for Chlamydia trachomatis and Neisseria gonorrhoeae. A potassium hydroxide
      preparation was negative for fungi, and an ulcer swab for bacterial culture
      revealed usual flora. Of note, the PCR assay for Epstein-Barr virus was not
      performed on ulcer cells. The patient was referred to the department of
      dermatology, and results of a physical examination showed copious white mucoid
      discharge and a 2-cm ulceration of the left labia minora (Figure, panel A). Two
      smaller pinpoint ulcerations and swelling of the left labia minora were also
      noted. The lesions were clinically indistinguishable from the genital aphthous
      ulcers of patients with complex aphthosis (recurrent, severe aphthous ulcers on
      oral or genital mucosa). A diagnosis of ulcus vulvae acutum was made, and
      treatment was started with clobetasol 0.05% ointment (4 times daily) and
      lidocaine gel as needed. Four days later, the patient reported marked symptomatic
      improvement. Physical examination showed near resolution of the large vulvar
      ulceration (Figure, panel B). The patient tapered use of clobetasol ointment over
      the next several days until the ulcerations healed completely. Two months after
      her initial episode, the patient again had 3 small vulvar erosions after symptoms
      that included low-grade fever, malaise, and vomiting. She did not receive
      oseltamivir for this illness; clobetasol ointment was applied 4 times daily, and
      the vulvar erosions ameliorated within a few days. Her constitutional symptoms
      resolved without treatment. The patient has not experienced any further episodes
      of vulvar ulcerations in the 18 months after the most recent treatment.

PMID- 18327009
TI  - Tacrolimus-induced hyperpigmentation in a patch of vitiligo.
AB  - A 10-year-old boy had vitiligo vulgaris involving limited areas and was
      prescribed topical tacrolimus ointment (0.03%), as the lesions were present in
      the infraorbital area in addition to other areas including the arms, thighs, and
      around the knees and ankles. Within 2 months of starting treatment, he had
      evidence of diffuse repigmentation of all the patches of vitiligo. Two months
      later, all the lesions repigmented completely with excellent color matching
      except those in the infraorbital area. The parents were anxious due to brownish
      hyperpigmentation in the previous patch of vitiligo in infraorbital area
      (Figure). He had no irritation or burning sensation in the areas of application.
      There was no history of photosensitivity. The patient was applying tacrolimus
      once at night, and no photoprotection was advised. Due to location of the lesion
      in the infraorbital area, a cosmetically important site, the parents did not
      consent for punch biopsy. The hyperpigmentation was temporary, with reappearance
      of depigmentation within 1 month of discontinuing topical tacrolimus application.

PMID- 18327011
TI  - Academic medicine and the superhero: to involve, inspire, and challenge.

PMID- 18327010
TI  - The safety and efficacy of high-dose alefacept compared with a loading dose of
      alefacept in patients with chronic plaque psoriasis.
AB  - OBJECTIVES: Alefacept is a biologic response modifier indicated for moderate to
      severe psoriasis; it has been available since 2003. It is typically administered
      in a dosing regimen of 15 mg intramuscularly (IM) weekly for 12 weeks. The
      purpose of this study was to determine whether a higher dose may be more
      beneficial in achieving a 75% reduction in the Psoriasis Area and Severity Index
      (PASI 75). A secondary objective of this study was to examine whether increasing
      the dose during the initial course of alefacept would reduce the time to onset of
      efficacy and overall response rate. Two separate dosing regimens are evaluated in
      this study: 30 mg IM for 6 weeks followed by 15 mg IM for 6 weeks (group 1) and
      alefacept 30 mg IM weekly for 12 weeks (group 2). METHODS: Efficacy was assessed
      using the PASI, Physician Global Assessment, body surface area, and photographic
      evaluation of a target lesion. A total of 20 patients enrolled and were
      randomized, 16 of whom completed the study. Data analyses were performed on a per
      protocol basis. RESULTS: Overall, the mean PASI scores progressively decreased,
      with 43.8% reaching a 50% reduction in the PASI (PASI 50) at week 14 evaluation.
      Of these participants, 37.5% were in group 1 and 50% were treated with alefacept
      30 mg IM for 12 weeks (group 2). Although our sample size was small, 12.5% of
      patients (one patient in each treatment arm) reached PASI 75. The most common
      adverse events encountered in this trial were mild infection, headache, pruritus,
      and erythroderma. There were no infections associated with a CD4(+) cell count
      <250 cells/mm(3). CONCLUSIONS: There was no difference between the treatment
      groups in achieving PASI 50 or PASI 75. In addition, in our small population, the
      higher doses of alefacept were associated with increased adverse effects,
      including erythroderma.

PMID- 18327012
TI  - Bullous eruption in a patient infected with the human immunodeficiency virus.
AB  - A 30-year-old man diagnosed with human immunodeficiency virus (HIV) infection 10
      years earlier, presented with large tense blisters associated with minimal
      itching of 10 days' duration. He had no history of oral or genital erosions or
      ulcerations and showed no symptoms of HIV-related illnesses. Highly active
      antiretroviral therapy (HAART) had been started 6 weeks earlier when his CD4
      count was 116/mL. He initially received nevirapine 200 mg once daily; after 2
      weeks with no skin eruptions or other adverse reactions, the dose was increased
      to 200 mg twice daily. Other components of his HAART included lamivudine and
      stavudine. The patient was not taking any other prescription or alternative
      medicines. During the past year, he experienced 4 episodes of intensely itchy
      urticarial lesions that subsided with antihistamines. The present episode of
      bullous lesions was also preceded by urticarial lesions. On examination, he had
      multiple, large, tense bullae over relatively normal-looking skin involving all
      parts of the body (Figure 1). There were a few well-defined erosions. Nikolsky
      and bullae spread signs were negative, and no oral or genital erosions or
      ulcerations were noted. Results of a complete blood count, renal and liver
      function tests, and chest x-ray were within normal limits. Skin biopsy from one
      of the blisters showed a subepidermal bulla filled with eosinophils and
      polymorphonuclear leukocytes (Figure 2). The underlying dermis showed
      perivascular inflammatory infiltrate composed of polymorphonuclear and
      lymphomononuclear cells. The overall features were suggestive of bullous
      pemphigoid. A direct immunofluorescence test could not be done because of
      possible risk of cross-infection to the operator of the cryostat. Workup for
      herpes simplex virus and cytomegalovirus infection also could not be performed.
      HAART was discontinued temporarily with the suspicion that it was the causative
      factor. The patient was started on oral prednisolone 40 mg/d and topical
      clobetasol propionate (0.05%). Within 1 week of treatment, he had significant
      improvement with almost complete disappearance of the lesions. A few small, tense
      vesicles continued to appear between. Once the lesions completely disappeared,
      the prednisolone was gradually tapered off and all the components of HAART were
      resumed. The patient did well without any recurrence of lesions, thus virtually
      excluding HAART as the cause of the bullous pemphigoid-like eruptions.
      Subsequently, he did not return for follow-up.

PMID- 18327013
TI  - Expression of vinculin in autoimmune cutaneous diseases.
AB  - BACKGROUND: Reports have appeared that sera of patients with systemic autoimmune
      disorders have demonstrated autoantibodies to vinculin. OBJECTIVE: To determine
      the presence and distribution of vinculin in the skin of patients with cutaneous
      autoimmune disorders. METHODS: Semiquantitative immunohistochemistry
      investigations for presence of vinculin were conducted on skin biopsy specimens
      from patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), and various
      collagen vascular diseases, and from healthy controls. RESULTS: Results of
      staining for vinculin were positive in 2 of 7 PV patients, 6 of 9 BP patients,
      and all 6 cutaneous autoimmune patients. Staining results were negative in all
      controls. Strong immunostaining to vinculin was found in 3 of 6 vinculin-positive
      BP patients and 5 of 6 vinculin-positive cutaneous autoimmune patients.
      CONCLUSIONS: The expression and distribution of vinculin are accentuated in
      patients with various skin autoimmune diseases and appear to be stronger in
      diseases involving the basement membrane, where it is thought to be relatively
      more important than in other skin disorders.

PMID- 18327014
TI  - Xyzal (levocetirizine dihydrochloride).

PMID- 18327015
TI  - Executive functions in pathologic gamblers selected in an ecologic setting.
AB  - BACKGROUND: Recent studies have reported deficits in measures of decision making
      in pathologic gamblers (PGs) suggesting an involvement of the prefrontal cortex
      in the pathophysiology of this disorder. As only 7% to 12% of PGs are thought to
      seek treatment, most of the studies have relied on few specifically selected
      groups of PGs recruited from psychiatric units who were undergoing or seeking
      treatment and therefore their results are poorly representative of the general PG
      population. METHODS: The present study compared decision making and executive
      functions among 11 PGs who were selected from an ecologic setting and 11 healthy
      controls. RESULTS: The PG group selected fewer advantageous cards on a decision
      making task, the Iowa Gambling Task, and made more commission errors on the Go-No
      Go task, a test of inhibitory control, compared with controls. CONCLUSIONS: The
      impairments in decision making are similar to those previously reported in
      individuals with prefrontal lesions and treatment-seeking PGs. PGs also presented
      impairment in tasks of inhibitory control suggesting an involvement of the
      prefrontal cortex in the pathophysiology of pathologic gambling (PG). The
      deficits in decision making and inhibition of irrelevant information observed in
      this study may have distinct but additive effects upon the development of PG
      behavior.

PMID- 18327016
TI  - Art in the eye of the beholder: the perception of art during monocular viewing.
AB  - OBJECTIVE: To explore whether monocular viewing affects judgment of art.
      BACKGROUND: Each superior colliculus receives optic nerve fibers primarily from
      the contralateral eye, and visual input to each colliculus activates the
      ipsilateral hemisphere. In previous studies, monocular viewing influenced
      performance on visual-spatial and verbal memory tasks. METHOD: Eight college
      educated subjects, 6 men and 2 women, monocularly viewed 10 paintings with the
      right eye and another 10 with the left. Subjects had not previously seen the
      paintings. Each time, 5 paintings were abstract expressionist and 5 were
      impressionist. The orders of eye viewing and painting viewed were
      pseudorandomized and counterbalanced. Subjects rated on a 1 to 10 scale 4
      qualities of the paintings: representation, aesthetics (beauty), novelty, and
      closure (completeness). RESULTS: Paintings in the abstract expressionist style
      had a significant difference in the rating of novelty; the paintings were rated
      more novel when viewed with the left eye than with the right eye. There was a
      trend for rating paintings as having more closure when viewing with the right eye
      than with the left. Impressionist paintings show no differences. CONCLUSIONS:
      Monocular viewing influences artistic judgments; novelty being rated higher when
      viewed with the left eye. Asymmetric projections from each eye and hemispheric
      specialization are posited to explain these differences.

PMID- 18327017
TI  - Subjective time in near and far representational space.
AB  - OBJECTIVE: We set out to measure healthy subjects' estimates of temporal duration
      during the imagination of left and right sides of an object located in either
      near or far representational space. BACKGROUND: Duration estimates during the
      observation of small-scale scenes are shorter than those during the observation
      of the same scenes presented in a larger scale. It is not known whether a similar
      space-time relationship also exists for objects merely imagined and whether
      subjective time varies with a forced focus on either the left or the right side
      of a mental image. METHODS: Eyes closed, 40 healthy, right-handed subjects (20
      women) had to imagine a standard Swiss railway clock either at a distance of 30
      cm or 6 m. They were required to focus on the imagined movement of the second
      hand and provide estimates of elapsed durations of 15 and 30 seconds. Separate
      estimates for the left and right side of the clockface were obtained. The
      magnitude of implicit line bisection error was assessed in a separate task.
      RESULTS: Irrespective of side of the clockface, duration estimates were shorter
      for the clockface imagined in far space than for the one imagined immediately in
      front of the inner eye. For men, but not women, duration judgments (left relative
      to right side of the clockface) correlated with relative lengths of left and
      right line segments in the bisection task. CONCLUSIONS: Subjective time seems to
      run faster during the inspection of a small-size compared with a larger-size
      mental image. This finding underlines the equivalence of the laws that guide both
      exploration and representation of space. Together with the observed correlation
      between spatial and temporal measures of lateral asymmetries, the result also
      illustrates the conceptual similarities in the processing of space and time. The
      normative data presented here may be useful for clinical applications of the
      paradigm in patients with hemispatial neglect or a distorted perception of time.

PMID- 18327018
TI  - Progressive asymmetric apraxic agraphia.
AB  - BACKGROUND/OBJECTIVES: Patients with apraxic agraphia cannot correctly form the
      letters needed to write words but can correctly spell words orally. Apraxic
      agraphia (AA) is often associated with ideomotor apraxia and most commonly
      induced by stroke, but can be associated with degenerative diseases. In
      degenerative diseases, asymmetrical apraxic agraphia (AAA) has rarely been
      reported as one of the presenting features. The purpose of this report is to
      describe a case series of 3 patients who presented with an AAA, and also to
      elucidate some of the cognitive mechanisms of this disorder. METHODS/RESULTS:
      These patients, who were not aphasic or alexic, developed agraphia as one of
      their earliest reported symptoms. They also demonstrated an asymmetrical
      ideomotor apraxia. Their agraphia was characterized by the inability to form
      letters, with the preserved ability to orally spell. To learn if this disorder
      was being caused by a loss of spatial-movement representations versus an
      impairment of implementation, one patient was asked to determine if gestures made
      by the examiner were correct or incorrect, and also to image the structure of
      letters. He performed poorly on both these tests and he also demonstrated an
      asymmetrical agraphesthesia. CONCLUSIONS: These patients' AAA might be the
      beginning of the corticobasal degeneration syndrome, but future studies will have
      to examine the brain pathology associated with AAA. Our patient's poor
      performance on pantomime recognition and imagery suggests that his apraxia is
      related to a deterioration of his graphemic and transitive spatial movement
      representations. The recognition of numbers written on the hand with eyes closed
      might also depend on having intact movement representations and his asymmetrical
      agraphesthesia might also be related to his AAA.

PMID- 18327019
TI  - Development of a standardized scoring method for the Graphic Sequence Test
      suitable for use in psychiatric populations.
AB  - Although the graphic version of the Alternating Sequences Test which was
      introduced by Luria exists for years little has been done to standardize it. The
      aim of the current study was to develop a novel and detailed standardized method
      of administration and scoring. The study sample included 93 normal control
      subjects (53 women and 40 men) aged 35.87+/-12.62 and 127 patients suffering from
      schizophrenia (54 women and 73 men) aged 34.07+/-9.83. The psychometric
      assessment included the Positive and Negative Symptoms Scale the Young Mania
      Rating Scale, and the Montgomery-Asberg Depression Rating Scale. A scoring method
      was developed and was based on the frequencies of responses of healthy controls.
      Cronbach alpha and test-retest and interrater reliability were very good. Two
      indices and 6 subscales of the Standardized Graphic Sequence Test were eventually
      developed. The Standardized Graphic Sequence Test seems to be a reliable, valid,
      and sensitive to change instrument based on Luria's graphic sequence test. The
      great advantage of this instrument is the fact that it is paper and pencil,
      easily administered and little time consuming. Further research is necessary to
      test its usefulness as a neuropsychologic test.

PMID- 18327020
TI  - Executive dysfunction and neuropsychiatric symptoms predict lower health status
      in essential tremor.
AB  - OBJECTIVE: To evaluate the hypothesis that increased neuropsychiatric distress
      and cognitive impairment are associated with lower perceived health status in
      essential tremor (ET). BACKGROUND: Many patients with ET experience nonmotor
      complications, including lower perceived health status and poor health-related
      quality of life, which are associated with tremor severity, age, and personality
      factors. No studies, however, have examined the potential contribution of
      neuropsychiatric symptoms and cognitive deficits to health status in ET. METHOD:
      Forty-five patients with ET underwent comprehensive neurologic and
      neuropsychologic evaluations, including self-report measures of physical and
      psychosocial health status (ie, the Sickness Impact Profile) and neuropsychiatric
      distress (ie, the Profile of Mood States). RESULTS: A series of hierarchical
      multiple regressions showed that after considering the effects of ET disease
      severity, lower vigor, and deficits in executive functions were independently
      predictive of poorer physical health status, whereas increased symptoms of
      depression were uniquely associated with lower psychosocial health status.
      CONCLUSIONS: Findings indicate that reduced vigor (ie, apathy), executive
      deficits, and depression are important predictors of poorer perceived health
      status in ET. Given the prevalence of such nonmotor symptoms, these data
      highlight the potential value of considering neuropsychiatric and neurocognitive
      assessments in the management of patients with ET.

PMID- 18327021
TI  - Catatonic signs in Gilles de la Tourette syndrome.
AB  - BACKGROUND: Catatonia describes the clustering of specific movement and
      behavioral abnormalities of both the hypokinetic and hyperkinetic nature.
      Originally described in association with schizophrenia, catatonic signs have been
      reported in a wide range of neuropsychiatric conditions. AIM: In this study, we
      examined the phenomenologic expression and significance of catatonic signs in a
      nonpsychotic patient group, 55 adults with Gilles de la Tourette syndrome (GTS).
      METHODS: The Bush-Francis Catatonia Rating Scale (BFCRS) and standardized
      psychometric instruments were used to assess the presence and severity of
      catatonic signs, motor and vocal tics, and comorbid psychopathologies. RESULTS:
      The majority of the GTS patients (87%) expressed catatonic signs sufficient for
      its diagnosis with the BFCRS. In general, positive catatonic signs, including
      echophenomena, perseveration, and excitement, exceeded the more classic negative
      symptoms (eg, posturing and stupor). The presence of comorbid attention-deficit
      and hyperactivity disorder, but not tic severity, was associated with higher
      BFCRS scores. CONCLUSIONS: The core phenomenology of GTS includes specific
      behavioral and motor features of catatonia, enhancing insight into
      neuropathologic substrates of these conditions. Our finding of an association
      with attention-deficit and hyperactivity disorder suggests that catatonia
      expression in GTS reflects a conjunction of cognitive and motor dysregulation.

PMID- 18327022
TI  - Musical hallucinations after left temporal lobectomy.
AB  - BACKGROUND: Musical hallucinations (MHs) are rare and most often described in
      patients with hearing loss, female sex, older age, and various brain pathologies,
      including epilepsy. CASE HISTORY: We describe a unique case in which, after
      successful left temporal lobectomy for refractory epilepsy and subsequent
      ototoxic therapies, a 49-year-old man experienced the onset of songs replaying
      constantly in his mind for days to weeks. He had intractable partial epilepsy
      since age 26. Presurgical neurodiagnostic evaluations revealed a left temporal
      focus, left hippocampal magnetic resonance imaging abnormalities, bilateral
      language representation, and cognitive deficits lateralized to the left
      hemisphere. He underwent a partial left temporal lobectomy but required repeated
      antibiotic courses for postoperation bone flap infections, resulting in tinnitus.
      Surgery led to near seizure-freedom, plus improved cognitive and emotional
      function. Pathology revealed focal cortical dysplasia. Six months postsurgery,
      during antibiotic treatment, he began to hear songs replaying in his head, which
      increased in frequency over ensuing years. CONCLUSIONS: We report, to our
      knowledge, the first case of MHs associated with temporal lobectomy for epilepsy.
      This patient had multiple risk factors for these unwanted musical experiences,
      including epilepsy, mild neuropsychiatric dysfunction, and tinnitus plus hearing
      loss. Possible mechanisms for MHs are discussed.

PMID- 18327023
TI  - Increased left prefrontal activation during staring/mutism episodes in a patient
      with resistant catatonic schizophrenia: a near infrared spectroscopy study.
AB  - OBJECTIVE: To present the first near infrared spectroscopy (NIRS) study of a
      patient with resistant catatonic schizophrenia during residual episodes of
      catatonia-related symptoms. BACKGROUND: Functional imaging studies generally
      point to a decreased cortical activation in catatonic patients, with the notable
      exception of increased orbitofrontal/medial prefrontal activity elicited by
      negative stimuli. METHODS: Cortical activity of the left anterior prefrontal area
      was recorded with a Techen 4 x 4 NIRS apparatus. Four episodes of staring/mutism
      were recorded and averaged. Compared with normal activity, these episodes were
      characterized by increased cortical activation. CONCLUSIONS: Within its
      methodologic limitations, the present observation suggests that increased
      anterior prefrontal activation in catatonic patients is not specific to negative
      stimuli. Known functions of the anterior prefrontal cortex such as self
      monitoring, reallocation of attention, or conflict resolution might underlie
      these findings. These also attest to the potential of NIRS for functional imaging
      of vulnerable subjects.

PMID- 18327024
TI  - Encephalitis and catatonia treated with ECT.
AB  - OBJECTIVE: To describe 2 cases of encephalitis with neuropsychiatric symptoms
      including catatonia, compounded by neuroleptic use for delirious agitation
      culminating in malignant catatonia responsive to electroconvulsive therapy (ECT).
      BACKGROUND: Neuropsychiatric symptoms including catatonia can be manifestations
      of limbic encephalitis and encephalitides of unidentified etiology, including
      encephalitis lethargica. Catatonic features are often difficult to appraise in
      this context. This can easily lead to the use of neuroleptics, which may
      precipitate worsening of catatonia. METHOD: Medical, neurologic, and psychiatric
      histories, physical examination findings, results of laboratory, imaging and
      neurophysiologic investigations, and treatment response with medications and ECT
      were recorded. RESULTS: Both patients showed significant improvement with ECT.
      CONCLUSIONS: Malignant catatonia can complicate encephalitis lethargica and
      idiopathic limbic encephalitis, which already carry high mortality rates. When
      neuroleptics are used for agitation in cases of encephalitis, physicians must be
      wary of precipitating malignant catatonia and neuroleptics should be discontinued
      when such a danger emerges. Although lorazepam is helpful in treating catatonia,
      it may not suffice, as in the cases presented. ECT deserves serious consideration
      early in the course of malignant catatonia and for catatonia nested in
      encephalopathy secondary to encephalitis, unresolved with lorazepam.

PMID- 18327025
TI  - Aerophagia and belching after herpes simplex encephalitis.
AB  - The etiology of abnormal belching is not known. Currently, it is being subsumed
      under "functional gastroduodenal disorders." Here, we report the unusual case
      history of a patient who developed aerophagia and consecutive excessive belching
      in association with herpes simplex encephalitis. The case report adds to the
      limited information about potential organic geneses of belching. Implications for
      possible medical therapies are discussed.

PMID- 18327027
TI  - Tumour boards/multidisciplinary head and neck cancer meetings: are they of value
      to patients, treating staff or a political additional drain on healthcare
      resources?
AB  - PURPOSE OF REVIEW: This article reviews the literature on the management of head
      and neck cancer using multidisciplinary team meetings as well as addressing the
      question of whether or not this organization is of benefit to the patients and
      treating staff and if it is cost efficient. RECENT FINDINGS: The
      multidisciplinary team has developed because of the complexity of clinical workup
      and treatment of head and neck cancer for which no single physician can claim to
      master all the training and skills necessary to treat the patients. The
      multidisciplinary team ensures that the professional efforts are coordinated and
      timely, thus ensuring the best results for patients. The multidisciplinary team
      usually involves a centralization of care with specialization, which benefits the
      outcome of treatment as well as enabling the development of clinical pathways to
      minimize complications, and improving on cost effectiveness. SUMMARY: The
      multidisciplinary team has become more and more an integral part of the clinical
      pathway for a patient with head and neck cancer in many European countries. This
      is cost effective and benefits patient outcomes.

PMID- 18327028
TI  - The missing member of the head and neck multidisciplinary team: the psychologist.
      Why we need them.
AB  - PURPOSE OF REVIEW: The aim of this article is to present the latest published
      material to demonstrate the service activity for the head and neck cancer team.
      RECENT FINDINGS: There is a growing literature confirming the importance of many
      psychological issues that impact on the experience of the patient following
      diagnosis and treatment of head and neck cancer. Although there may be some
      recognition by some members of the multidisciplinary team to involve
      psychological services there is now ample evidence from the results of this
      literature to argue that the psychologist should feature as a full member of the
      multidisciplinary team. Activities would include formal assessment of
      psychological features of the patient and carer, interpretation of psychometric
      data including distress and quality of life inventories, design and
      implementation of interventions and supervisory support for the work pressures
      experienced by the multidisciplinary team. SUMMARY: The care of the head and neck
      patient involves a large variety of psychosocial factors. Many of these issues
      require formal assessment and interpretation that the professional psychologist
      can input into the care programmes for these patients.

PMID- 18327029
TI  - Modern methods to predict costs for the treatment and management of head and neck
      cancer patients: examples of methods used in the current literature.
AB  - PURPOSE OF REVIEW: In the last year, several groups have used various methods to
      calculate economic costs to patients with early- and late-stage head and neck
      cancer, cost comparisons of palliative treatments, patient time costs associated
      with cancer care, and the impact of new diagnostic technologies which need formal
      cost-effectiveness assessment to determine their value. RECENT FINDINGS: Late
      stage oral and oropharyngeal cancer treatment is more expensive than early-stage.
      Photodynamic therapy is cost-effective for esophageal cancer. Head and neck
      cancer patients spend more time receiving care than control cancer. Multimodal
      therapy for oropharynx cancer has a higher inpatient utilization than a radio
      (chemo) approach. Positron emission tomography in combination with computed
      tomography has a high accuracy, positive predictive value, and ability to find
      unknown primaries. Soluble CD44 and methylation status are highly sensitive and
      specific for detecting head and neck cancer. The Washington University head and
      neck cancer comorbidity index was successful at predicting 5-year costs of head
      and neck cancer. SUMMARY: Evidence-based studies to inform head and neck cancer
      care providers are limited. As this available literature proliferates, it should
      inform providers and policy makers about optimizing the quality and cost of
      healthcare expenses.

PMID- 18327030
TI  - Should there be more molecular staging of head and neck cancer to improve the
      choice of treatments and thereby improve survival?
AB  - PURPOSE OF REVIEW: Overall survival of head and neck squamous cell carcinoma
      patients on the whole has not dramatically improved in the last 30 years. One of
      the reasons is that tumour, node, metastasis classification is probably in some
      cases inadequate, since similar cases under a clinico-pathological point of view,
      may differ widely in prognosis. The most important reason for this is probably
      the extreme biological heterogeneity, which leads to a lack of consistency in
      treatment planning. The aim of the present review is to delineate the advances
      and the perspectives of clinical use of molecular characterization, which is an
      attempt to break through such molecular heterogeneity and to define, together
      with tumour, node, metastasis classification, homogeneous groups of patients for
      prognostic stratification and treatment selection. RECENT FINDINGS: Among the
      markers evaluated in the last years, some have revealed particular promise.
      Epidermal growth factor receptor is probably the most reliable molecular marker
      at present, retaining its prognostic value independently from primary treatment.
      The p53 gene, the p53 protein being the main effector of DNA damage induced
      apoptosis, is probably the best predictor of radio/chemosensitivity. SUMMARY:
      Even if clinical tumour, node, metastasis classification will probably retain its
      significance, it is now becoming possible, by molecular markers, to acquire
      biological information about host and tumour, to break through the above-cited
      molecular heterogeneity and eventually to optimize the choice of treatment.

PMID- 18327031
TI  - The clinician's expectations from the use of positron emission
      tomography/computed tomography scanning in untreated and treated head and neck
      cancer patients.
AB  - PURPOSE OF REVIEW: We reviewed articles published in the last 2 years on the
      subject of positron emission tomography (PET)/computed tomography (CT) use in
      head and neck cancer patients. The focus is on helping otolaryngologists decide
      when to use PET/CT and how to apply it to head and neck cancer patient
      management. RECENT FINDINGS: The main themes in the literature pertaining to
      PET/CT and head and neck cancer are use in untreated patients, evaluating early
      stage patients with N0 necks, use in cancer of unknown primary origin, detecting
      synchronous lesions and distant metastases, and use in previously treated
      patients. SUMMARY: Evidence is mounting in both otolaryngology and radiation
      oncology literature to support PET/CT as the preferred imaging modality for
      certain patients with head and neck cancer. We should consider PET/CT's superior
      accuracy and ability to improve patient management. It is our opinion that this
      imaging modality increases the otolaryngologist's and radiation oncologist's
      confidence when treating head and neck cancer patients and leads to appropriate
      management changes. Certainly, additional prospective trials would help validate
      these opinions.

PMID- 18327032
TI  - Salvage surgery after failed primary concomitant chemoradiation.
AB  - PURPOSE OF REVIEW: Primary treatment of many head and neck cancers is shifting to
      nonsurgical modalities with concomitant chemoradiation becoming increasing
      prevalent. With this change, surgery is moving to a role as a salvage treatment
      modality. As a result of this shift, it is important to understand the issues
      surrounding surgical salvage after chemoradiation. RECENT FINDINGS: Studies have
      consistently found that salvage surgery after chemoradiation carries a high
      complication rate, higher than either primary surgery or salvage surgery after
      radiation alone. There are very few reports on the success rate of salvage
      surgery after failed primary concurrent chemoradiation, but what little data we
      have seems to suggest success rates approximate success rates for salvage after
      radiation therapy. There are also reasons to believe that efficacy of salvage
      surgery varies by stage and site of disease. Also, fundamental differences in the
      nature of cancer after failed primary therapy have been elucidated by recent
      studies. SUMMARY: While salvage surgery is fraught with higher morbidity and
      lower efficacy than primary surgery, it remains the only potentially curative
      option available to patients who have failed 'organ preservation' primary
      therapy. We review issues to consider when managing these challenging patients.

PMID- 18327033
TI  - Organ-preservation surgery following failed radiotherapy for laryngeal cancer.
      Evaluation, patient selection, functional outcome and survival.
AB  - PURPOSE OF THE REVIEW: Although radiotherapy is a well codified treatment for
      laryngeal carcinomas, the management of local recurrence after failed
      radiotherapy remains controversial. Total laryngectomy is the classical salvage
      surgical approach. Recent evidence showed that selected laryngeal recurrences may
      be successfully treated with partial laryngectomies with comparable survival
      rates, acceptable morbidity, tracheostomy closure, effective swallowing, and
      satisfactory voice intelligibility. RECENT FINDINGS: Recurrent laryngeal
      carcinoma after radiotherapy failure requires a comprehensive clinical,
      radiological and pathological restaging. Strict selection criteria are mandatory
      for the identification of radiotherapy failure cases amenable to conservative
      laryngeal surgery. Although larger series confirmation is necessary, conservative
      salvage surgery seems definitely promising. Salvage endolaryngeal laser surgery
      after irradiation failure allows in selected cases a mean local control rate of
      65%. Selectively, supracricoid laryngectomy can be a flexible alternative to
      salvage total laryngectomy being conservative of laryngeal functions (mean local
      control rate of 85%). Selected laryngeal recurrences can be correctly treated
      also with vertical or horizontal supraglottic laryngectomies. In partial
      laryngectomies, intraoperative frozen sections are mandatory: postoperatively
      permanent sections have to confirm all margins. SUMMARY: When proper selection
      criteria for conservative salvage laryngeal surgery are used, laryngeal function
      can be preserved with oncological efficacy also after radiotherapy failure.

PMID- 18327034
TI  - Laryngeal and hypopharyngeal carcinomas after (chemo)radiotherapy: a diagnostic
      dilemma.
AB  - PURPOSE OF REVIEW: During recent years, (chemo)radiotherapy has evolved into a
      primary treatment modality for both early and advanced laryngeal and
      hypopharyngeal carcinomas. Head and neck surgeons will be concerned more
      frequently with patients presenting symptoms and signs suggesting recurrent tumor
      or complications of (chemo)radiotherapy. RECENT FINDINGS: Analysis of histologic
      characteristics and tumor spread of recurrent carcinomas on whole-organ slices of
      salvage laryngectomy specimens showed that recurrent laryngeal carcinomas are
      often present with multiple tumor foci dispersed in different regions;
      furthermore, they may develop beneath an intact mucosa. Only a few articles
      analyze the reliability of laryngoscopy and biopsy in detecting recurrences after
      (chemo)radiotherapy: the number of false negative biopsies is relatively high.
      The differentiation between radionecrosis and tumor recurrence is difficult by
      computed tomography scan and magnetic resonance imaging in many cases. Positron
      emission tomography-computed tomography and diffusion-weighted magnetic resonance
      imaging are promising diagnostic modalities to detect or exclude persistent or
      recurrent disease after (chemo)radiotherapy. SUMMARY: Endoscopy with biopsy,
      computed tomography scan and conventional magnetic resonance imaging present
      several deficiencies in diagnosing recurrent disease after (chemo)radiotherapy.
      New imaging modalities such as positron emission tomography-computed tomography
      and diffusion-weighted magnetic resonance imaging show promising results,
      increasing the diagnostic efficacy.

PMID- 18327035
TI  - The need for patients' endocrine function vigilance following treatment of head
      and neck cancer.
AB  - PURPOSE OF REVIEW: The aim of this article is to examine the need for screening
      of endocrine dysfunction following treatment of head and neck cancer. RECENT
      FINDINGS: The incidence of occult hypothyroidism following treatment of head and
      neck cancer is high. Patients who develop hypothyroidism after treatment may have
      an increased survival compared with patients who did not become hypothyroid.
      Because of the growing body of evidence that supports a permissive role for
      thyroid hormone in the growth of certain solid tumours thyroid hormone
      replacement therapy may not be indicated in patients with subclinical
      hypothyroidism and prior or current cancer. Although the incidence of
      hypoparathyroidism after treatment for head and neck cancer is low, testing of
      serum calcium is easily performed during thyroid function evaluation. The
      incidence of hypopituitarism after irradiation of the nasopharynx or skull base
      is very high warranting regular evaluation of endocrine functions. SUMMARY: Owing
      to the high incidence of endocrine dysfunction, all head and neck cancer patients
      who undergo treatment of the lower neck, nasopharynx or base of skull need
      regular endocrine evaluation during long-term follow-up to determine the need to
      start hormone replacement therapy and maintain optimal quality of life.

PMID- 18327036
TI  - Medullary thyroid carcinoma: surgical treatment advances.
AB  - PURPOSE OF REVIEW: In recent years new technologies have been proposed and
      applied in thyroid surgery, among these molecular diagnosis and endoscopic
      procedures. The authors review relevant medical literature published on the
      influence of these new techniques in the treatment of medullary thyroid cancer.
      Searches were last updated in October 2007. RECENT FINDINGS: Mutations of the RET
      proto-oncogene have been demonstrated to be causative of the familial form of
      medullary thyroid cancer. The number and type of recognized RET genetic mutations
      have grown over the last years, especially after the introduction of genetic
      screening in the work-up of all patients with medullary thyroid cancer.
      Prophylactic surgery for patients carrying a positive RET proto-oncogene is
      highly effective. Cervical endoscopic procedures have been recently described and
      applied for positive RET carriers: a video-assisted thyroidectomy with central
      compartment dissection (level 6) has proved feasible, safe and effective for
      these patients. SUMMARY: There have been some important papers in the recent
      literature that apply to many aspects of new technologies for medullary thyroid
      cancer treatment. This article discusses some of these articles, emphasizing
      where this literature makes new contributions and supports established
      recommendations.

PMID- 18327037
TI  - Polymorphous low-grade adenocarcinoma of the head and neck.
AB  - PURPOSE OF REVIEW: Polymorphous low-grade adenocarcinoma is an entity described
      in 1984. An increasing number of reports in the pathology literature since then
      have identified this as the second or the third most common minor salivary gland
      malignancy. The natural history of polymorphous low-grade adenocarcinoma is
      distinct from other malignant salivary tumours. The present review will identify
      the diagnostic difficulties, the treatment options and the treatment outcome of
      this tumour. RECENT FINDINGS: Polymorphous low-grade adenocarcinoma is a slow
      growing tumour that is locally invasive. The most common presentation is that of
      a lump in the oral cavity, usually on the palate. Diagnosis is established after
      a biopsy because cytological studies are not helpful. The morphological features
      can resemble pleomorphic adenoma and adenoid cystic carcinoma. Therapy is
      primarily wide surgical resection. The role of radiation therapy is not clear in
      the management of polymorphous low-grade adenocarcinoma. Metastases are rare and
      recurrences tend to occur more than 5 years after treatment, underlining the need
      for long-term follow-up. Recurrences can be successfully salvaged in more than
      50% of the cases. SUMMARY: Polymorphous low-grade adenocarcinoma is primarily a
      pathologic diagnosis. Surgical resection is the mainstay of treatment. Long-term
      follow-up of 10 years or more is essential to ensure local control.

PMID- 18327038
TI  - Merkel cell carcinoma: a review of management.
AB  - PURPOSE OF REVIEW: Merkel cell carcinoma is an uncommon but aggressive primary
      cutaneous neuroendocrine (small cell) carcinoma. The head and neck is a frequent
      site (50-60%) for presentation. The optimal treatment of patients with Merkel
      cell carcinoma remains debated with recent evidence adding support for a
      multimodality approach. Despite this the outcome for patients with unfavourable
      disease remains poor and in many series 25-50% of patients die as a direct result
      of Merkel cell carcinoma. RECENT FINDINGS: Wide excision (2-3 cm) of the primary
      lesion has been recommended, although achieving this is often impossible within
      the functional and cosmetic constraints of the head and neck. The well-documented
      responsiveness of this disease to radiotherapy and chemotherapy has strengthened
      the case for less radical surgery. Current best practice, as presented in recent
      publications, would support adjuvant wide-field radiotherapy, delivered after
      wide excision with negative microscopic margins, as best practice. The role of
      platinum-based chemotherapy remains under investigation. SUMMARY: Most patients
      with a Merkel cell carcinoma should be recommended wide-field adjuvant
      radiotherapy to encompass the primary site, in-transit tissue and first echelon
      lymph nodes following surgery. The benefit of adding chemotherapy is currently
      unproven and should be considered on an individual basis.

PMID- 18327039
TI  - Bibliography. Current world literature. Head and neck oncology.

PMID- 18327041
TI  - World Glaucoma Day, March 6, 2008: tackling glaucoma internationally.

PMID- 18327042
TI  - A novel method of fitting scleral lenses using high resolution optical coherence
      tomography.
AB  - PURPOSE: Case report study of a novel method of fitting large rigid gas-permeable
      lenses (cornea-scleral, mini-scleral, scleral). METHODS: Nine patients with
      different corneal and refractive conditions were fitted with scleral-type rigid
      gas-permeable lenses using high resolution ocular coherence tomography. All
      patients achieved excellent visual acuity and comfort. Lenses were well tolerated
      without significant complications. Three cases are discussed in detail. Two of
      the 3 patients had previously undergone fitting with trial lenses so that the
      different methods could be compared with respect to number of lenses used to
      achieve a final fit. CONCLUSIONS: High resolution biometry proved to be a highly
      useful fitting tool and seems to offer a more accurate and efficient alternative
      to fitting scleral-type lenses compared with the trial lens method.

PMID- 18327043
TI  - Hyper oxygen-permeable rigid contact lenses as an alternative for the treatment
      of pediatric aphakia.
AB  - PURPOSE: To establish the safety and efficacy of a hyper oxygen-permeable rigid
      contact lens material, Menicon Z, for the fitting of aphakic infant eyes.
      METHODS: A prospective study was performed on 16 eyes of 10 newly aphakic
      infants. Aphakic fittings were performed postoperatively with the Dyna Z
      intralimbal design of lenses, made exclusively from Menicon Z material for this
      study. Examinations were performed at 1 day, 1 week, 1 month, 3 months, and 6
      months, during which the lenses were used on a 1-week extended-wear basis. The
      following outcome measures were evaluated at each visit: Fit Characteristics,
      Ocular Integrity, Usability, and Contact Lens Integrity. RESULTS: When used for
      the treatment of pediatric aphakia, the Menicon Z material provided excellent Fit
      Characteristics, was not damaging to the ocular structures, was relatively easy
      to manipulate for caregivers, and maintained its integrity well throughout the
      course of the study. Because there were no observable increases in the rate of
      microbial infection during the course of the study, the hyper oxygen-permeable
      nature of the Menicon Z material seems to provide adequate corneal oxygenation
      for aphakic children when used on a 1-week extended-wear basis. CONCLUSIONS: The
      Menicon Z contact lens material provides a safe and effective alternative for the
      treatment of infants and children requiring aphakic correction. This hyper oxygen
      permeable material offers sufficient corneal oxygenation at the lens powers and
      thicknesses demanded by newly aphakic eyes combined with a low risk for
      associated complications.

PMID- 18327044
TI  - Long-term clinical outcomes for overnight corneal reshaping in children and
      adults.
AB  - PURPOSE: To retrospectively evaluate outcomes of overnight corneal reshaping
      (OCR) in children aged 12 years or younger compared to children older than 12
      years and adults at one practice to establish the efficacy and safety of OCR
      during a period of 51 months. METHODS: Examination records of OCR patients were
      reviewed for pretreatment data, including manifest refraction, keratometric
      readings, topography, corneal staining, and age at beginning OCR. Posttreatment
      records were reviewed for manifest refraction, unaided visual acuity,
      keratometric readings, topography, corneal staining, adverse events, and duration
      of OCR lens wear. RESULTS: Records of 296 OCR patients were evaluated. One
      hundred fifty-four (52.0%) patients were 12 years old or younger. Sixty-eight
      percent of all patients in the study were Asian, and almost 95% of the patients
      aged 12 years or younger were Asian. The patients aged 12 years or younger had a
      mean original spherical equivalent refractive error of -3.50 +/- 1.50 diopters
      (D). The patients older than 12 years had a mean original spherical equivalent
      refractive error of -3.20 +/- 1.50 D. Refractive changes were similar between the
      group aged 12 years or younger and the group older than 12 years (3.30 +/- 1.40 D
      vs. 3.10 +/- 1.40 D) (P=0.14). The mean unaided, binocular logMAR visual acuity
      was 0.03 +/- 0.06 (i.e., 20/20) for the group aged 12 years or younger and 0.02
      +/- 0.07 (i.e., 20/20) for the group older than 12 years. There were three
      adverse events during the study that did not result in a loss of best-corrected
      visual acuity. A total of 507 patient-years of wear was represented in the study.
      CONCLUSIONS: OCR resulted in comparable safety and efficacy in temporarily
      reducing myopia for children younger than 12 years as it is for children older
      than 12 years and adults.

PMID- 18327045
TI  - Effect of internal lubricating agents of disposable soft contact lenses on higher
      order aberrations after blinking.
AB  - PURPOSE: To investigate whether the polymer composition of disposable soft
      contact lenses affects sequential changes in higher-order aberrations (HOAs).
      METHODS: Fifteen subjects who wore disposable soft contact lenses with dryness
      related symptoms and 15 non-contact lens wearers were enrolled in this study.
      Ocular HOAs were measured for 60 seconds in each subject wearing a disposable
      etafilcon A lens (conventional lens) or a disposable etafilcon A lens with
      polyvinyl pyrrolidone (PVP) (lens with PVP) after 1 hour of contact lens wear.
      During the measurement, subjects were forced to blink every 10 seconds. The
      aberration data were analyzed in the central 4-mm diameter up to the sixth-order
      Zernike polynomials. Total HOAs, the fluctuation index (FI), and the stability
      index (SI) of the total HOAs over time were compared between the two groups. The
      subjective ocular dryness also was scored. RESULTS: In symptomatic wearers of
      disposable soft contact lenses, the total HOAs, the FI, and the SI with the lens
      with PVP were significantly (P=0.013, P=0.014, P=0.019, respectively) lower than
      with the conventional lens, whereas a significant (P=0.018) difference between
      the two lenses was observed only in the FI in non-contact lens wearers.
      Subjective ocular dryness with the lens with PVP significantly decreased compared
      with the conventional lens in both groups. CONCLUSIONS: Sequential measurement of
      HOAs may be a useful objective method to evaluate the effect of internal
      lubricating agents of disposable soft contact lenses on optical quality.

PMID- 18327046
TI  - Antecedent risk factors of xerophthalmia among Indian rural preschool children.
AB  - PURPOSE: To determine the risk factors of xerophthalmia among preschool children
      in rural India. METHODS: This cross-sectional study was carried out between
      January and June 1998 in the area of Bihta Primary Health Center in Bihar, India
      and included 4,205 preschool children from 14 villages. The main outcome measures
      were risk factors of xerophthalmia, namely socioeconomic status and a history of
      repeated diarrhea, measles, passing worms in stool, and respiratory tract
      infection. The survey module was developed from information provided in the World
      Health Organization's publication from global experts for ensuring feasibility,
      acceptability, time management, and reliability with a pilot study. A pretested
      questionnaire was then administered to the caregivers of 144 preschool children
      diagnosed by a specially trained investigator with vitamin A deficiency by
      interview technique. RESULTS: In a random sample of 4,205 preschool children, the
      overall prevalence of xerophthalmia, based on night blindness (XN) and Bitot
      spots (X1B), was of moderate public health importance, according to World Health
      Organization criteria, at 144 (3.42%). The proportion of those xerophthalmic
      children with known risk factors for malnutrition-associated xerophthalmia (i.e.,
      poverty, diarrhea, roundworm infection, measles, and respiratory infection) was
      described. A significant difference in magnitude was observed between more
      affluent families with a higher monthly average income and less affluent families
      (P<0.01). Children with a history of repeated diarrhea were incidentially less
      affected than those without this history, but this difference was not significant
      (P>0.5). Vitamin A-deficient children not passing worms accounted for only 22.50%
      of the sample versus a corresponding value in children passing worms, which was
      significantly high (P<0.01), at 87.50%. A history of measles or respiratory tract
      infection was not at all related as an antecedent risk factor. The caregivers
      were counseled in multiple sessions on vitamin A-rich, locally available, cost
      effective foods. CONCLUSIONS: The socioeconomic status of families, a history of
      passing roundworms in stool, and diarrhea were important antecedent risk factors
      in vitamin A- deficient preschool children. The undisputed long-term solution to
      prevent this nutrition-related, avoidable blindness lies in changing the dietary
      habits of the rural Indian population through behavior change communication by
      nutritional education, nutritional supplementation, and nutritional
      rehabilitation.

PMID- 18327047
TI  - In vitro susceptibilities of bacterial isolates from conjunctival flora to
      gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin.
AB  - PURPOSE: To evaluate and compare the in vitro susceptibilities of various
      fluoroquinolones (i.e., gatifloxacin, levofloxacin, tosufloxacin, and
      moxifloxacin) against conjunctival bacterial flora. METHODS: Two hundred sixty
      six bacterial isolates were collected from the conjunctival sacs of 251 eyes of
      224 patients (118 females and 106 males) ranging in age from 6 to 91 years old,
      who were scheduled for intraocular surgery at National Tokyo Medical Center. The
      minimum inhibitory concentration (MIC) was determined by broth dilution testing.
      RESULTS: Of 266 isolates, 258 (97.0%) strains were gram-positive bacteria and
      eight (3.0%) strains were gram-negative bacteria. The MIC90 values of
      gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin against alpha
      hemolytic streptococci were 0.39 microg/mL, 1.56 microg/mL, 0.39 microg/mL, and
      0.20 microg/mL, respectively. The MIC90 values of gatifloxacin, levofloxacin,
      tosufloxacin, and moxifloxacin against Staphylococcus aureus were 1.56 microg/mL,
      3.13 microg/mL, 0.78 microg/mL, and 0.78 microg/mL, respectively. The MIC90
      values of gatifloxacin, levofloxacin, tosufloxacin, and moxifloxacin against
      Staphylococcus epidermidis were 1.56 microg/mL, 3.13 microg/mL, 3.13 microg/mL,
      and 0.78 microg/mL, respectively. CONCLUSIONS: Although the clinical usefulness
      and efficacy of newer fluoroquinolones remains to be defined by clinical
      outcomes, the current study provides data for predicting relative in vivo potency
      among the fluoroquinolones.

PMID- 18327048
TI  - Clinical features and outcomes of Fusarium keratitis associated with contact lens
      wear.
AB  - PURPOSE: To describe the clinical features and outcomes among contact lens
      wearers with Fusarium keratitis. METHODS: A retrospective observational review of
      all cases of culture-proven Fusarium keratitis among contact lens wearers from
      three hospitals in Hong Kong Island were included. The clinical features, hygiene
      habits, and clinical outcomes were reviewed. RESULTS: Sixteen patients (17 eyes)
      were diagnosed with Fusarium keratitis associated with contact lens wear. One
      patient had bilateral involvement. Six patients had a central lesion; four had
      paraxial lesions; one had paraxial and peripheral lesions; and the rest had
      peripheral lesions. Ten (62.5%) patients reported using ReNu multipurpose
      cleaning solution. Most patients had poor contact lens hygiene habits. One
      patient required systemic antifungal treatment. No surgical intervention was
      required in any of the patients. CONCLUSIONS: The clinical features of Fusarium
      keratitis in contact lens wearers can be variable. Although fungal infection is
      reported rarely, clinicians should maintain a high index of suspicion for it when
      examining patients with contact lens-associated microbial keratitis. Education on
      proper contact lens care should be reinforced. Early and appropriate treatment
      may lead to satisfactory visual outcomes.

PMID- 18327049
TI  - IgE antibody on worn highly oxygen-permeable silicone hydrogel contact lenses
      from patients with contact lens-induced papillary conjunctivitis (CLPC).
AB  - PURPOSE: To investigate whether the level of IgE is increased in the eyes of
      patients during general contact lens-induced papillary conjunctivitis (CLPC)
      events, which involve enlarged papillae across the entire palpebral conjunctiva,
      or local CLPC events, in which papillae are confined to one or two parts of the
      area. METHODS: Worn contact lenses were collected and soaked in phosphate
      buffered saline. The levels of eluted IgE and IgE retained on contact lenses were
      detected by enzyme-linked immunosorbent assay. RESULTS: IgE was detected in 6 of
      12 cases of general CLPC, 8 of 21 cases of local CLPC, and none of 14 control
      contact lenses. The average level of eluted IgE was 0.54 +/- 1.06 IU/contact
      lens, 0.28 +/- 0.54 IU/contact lens, and 0.04 +/- 0.06 IU/contact lens for
      general CLPC, local CLPC, and the control group, respectively. The incidences of
      positive IgE were significantly higher in patients with CLPC (general and local)
      than in control subjects, but no statistical difference was found between general
      and local CLPC. Generally higher amounts of retained IgE were detected on contact
      lenses that had increased levels of eluted IgE. Contact lenses that were
      collected before or after a CLPC event did not show increased levels of IgE.
      CONCLUSIONS: The level of IgE is increased in the eyes of some patients during an
      acute event of CLPC. The similar incidence of IgE-positive cases and levels of
      IgE from general and local CLPC contact lenses suggest that the conditions may
      share similar causal pathways.

PMID- 18327050
TI  - Infectious keratitis in keratoconus with corneal hydrops without contact lens
      wear: a case report.
AB  - PURPOSE: Infectious keratitis after contact lens use is a known complication in
      cases of corneal hydrops. A case of infectious keratitis is reported in a case of
      keratoconus with corneal hydrops without any known predisposing factors. METHODS:
      Infectious keratitis was diagnosed in a 58-year-old man with spontaneous onset of
      pain, redness, photophobia, and decreased vision. There was no history of contact
      lens use or any ocular allergy. Noncoagulase staphylococci were cultured from the
      corneal scrapings, and treatment was started with fortified antibiotics. RESULTS:
      Response to treatment was noted, and the patient is awaiting keratoplasty.
      CONCLUSIONS: This case report highlights the occurrence of infectious keratitis
      in a case of keratoconus with corneal hydrops without any antecedent history of
      contact lens use.

PMID- 18327051
TI  - Pseudomonas keratitis associated with daily wear of silicone hydrogel contact
      lenses.
AB  - PURPOSE: To report two cases of pseudomonas keratitis associated with daily wear
      of silicone hydrogel contact lenses. METHODS: Medical records of two patients who
      developed pseudomonas keratitis while wearing silicone hydrogel lenses on a daily
      wear schedule are reviewed and discussed. RESULTS: A 13-year-old girl who wore
      ACUVUE Advance lenses (Johnson & Johnson Vision Care, Jacksonville, FL) 12 to 14
      hours daily developed a paracentral corneal ulcer in her left eye 4 months after
      beginning contact lens use. Cultures were positive for Pseudomonas aeruginosa.
      The ulcer responded to fortified antibiotics and resolved in 10 days. Best
      corrected visual acuity after resolution of the ulcer was 20/25. A 58-year-old
      woman with a 30-year history of rigid gas-permeable contact lens wear was
      refitted with O2 Optix lenses (CIBA Vision, Duluth, GA). Six months later, she
      had a 4.9 x 4.0 mm epithelial defect with an underlying stromal infiltrate in the
      right eye. Cultures were positive for P. aeruginosa. The ulcer responded to
      fortified antibiotics and resolved in 30 days. Best-corrected visual acuity after
      resolution of the ulcer was 20/30. CONCLUSIONS: Increased oxygen permeability
      associated with silicone hydrogel contact lenses may reduce, but does not
      eliminate, the risk of pseudomonas keratitis. Studies have yet to quantify the
      risk of keratitis associated with daily wear of these lens materials. Further
      study is necessary to identify the risks of complications with daily wear of
      silicone hydrogel lenses and to determine which factors may contribute to those
      risks.

PMID- 18327052
TI  - Corneal melting after use of nepafenac in a patient with chronic cystoid macular
      edema after cataract surgery.
AB  - This report describes a patient who developed a corneal melt after the use of
      nepafenac, a nonsteroidal antiinflammatory drug. An 82-year-old woman with
      chronic cystoid macular edema after cataract extraction and intraocular lens
      implantation in the left eye, which was clinically controlled with a topical
      nonsteroidal antiinflammatory drug, was initially treated with diclofenac sodium
      0.1% before being treated with nepafenac 0.1%. After 5 months of nepafenac use,
      the patient complained of pain, a foreign body sensation, and decreased vision in
      her left eye. The left eye showed a peripheral corneal ulcer with no stromal cell
      infiltration. The corneal ulcer was scraped and cultured to show epithelial cells
      and neutrophils with no growth of microorganisms. The nepafenac was discontinued,
      and a topical antibiotic and lubrication were used. After 2 months, the patient's
      visual acuity improved, and she had an intact epithelium and stable corneal
      thinning. To the authors' knowledge, this is the first case report of a corneal
      melt after the prolonged use of nepafenac to treat cystoid macular edema.

PMID- 18327053
TI  - Amiodarone-induced keratopathy: full-thickness corneal involvement.
AB  - PURPOSE: To report a case of amiodarone-induced keratopathy involving the entire
      cornea, including the endothelium. METHODS: Clinical case description and
      documentation with confocal laser scanning microscopy using the Heidelberg
      Retinal Tomography II (HRT II). RESULTS: A 65 year-old man with a history of
      blurred vision and seeing halos around lights had been treated with amiodarone
      for 6 years. Best-corrected visual acuity was 20/25 in each eye. Slitlamp
      examination of both eyes showed a bilateral, symmetric, whorllike pattern of
      brown deposits in the inferocentral corneal epithelium. Diffuse and fine deposits
      resembling keratic precipitates in the central part of the endothelial face were
      also detected. Examination of the lens, optic nerve, and fundus in each eye did
      not show any abnormalities that could be attributed to the amiodarone therapy.
      Severe endothelial deposition was documented with the confocal laser scanning
      microscope of the HRT II. CONCLUSIONS: Amiodarone-induced keratopathy with
      confluent and diffuse endothelial deposition is rare, and it may be indicative of
      a more severe toxicity associated with amiodarone.

PMID- 18327054
TI  - Standardized nursing terminologies can transform practice.

PMID- 18327055
TI  - Evidence synthesis: the good, the bad, and the ugly.

PMID- 18327056
TI  - The Robert Wood Johnson Executive Nurse Fellows Program: a model for learning in
      an executive master of science in nursing program.

PMID- 18327058
TI  - Is the HESI Exit Examination useful in service settings?

PMID- 18327059
TI  - Why do nurse managers stay? Building a model of engagement: part 1, dimensions of
      engagement.
AB  - The short tenure of nurse managers suggests the urgent need for a new model to
      understand and build engagement that translates into longevity and excellence in
      nurse managers. The authors report data from a national qualitative study, funded
      by the Robert Wood Johnson Foundation, of 30 outstanding long-time nurse managers
      in 6 settings and offer patterns of individual and cultural elements linked to
      engagement. Part 1 describes the dimensions of individual engagement along with
      the implications for developing and sustaining nurse managers. In Part 2, which
      will be available in April 2008, the authors will give details on the
      organizational factors that contribute to engagement of nurse managers and the
      applications for building cultures of engagement.

PMID- 18327060
TI  - Sleepless in America: nurse managers cope with stress and complexity.
AB  - Although nurse managers play a pivotal role in creating work environments for
      staff nurses, performance expectations for nurse managers practicing in acute
      care hospitals may be unrealistic. The authors discuss nurse manager interview
      data showing that these expectations are increasing nurse manager perceptions of
      stress, making coping more difficult, and potentially harming nurse manager and
      work environment well-being.

PMID- 18327061
TI  - The effect of consistent nursing shifts on teamwork and continuity of care.
AB  - To attract nurses to the workforce, scheduling of nurses on patient care units
      has evolved into a mixture of 4-, 6-, 8-, and 12-hour shifts. The result is
      chaotic as staff members come and go at varying times, creating the need for
      multiple handoffs and reassignment of patients. Effective teamwork and continuity
      of care are difficult, if not impossible, to achieve under these circumstances.
      The authors describe the effect of using just 1 shift length for all nursing
      staff.

PMID- 18327062
TI  - Showcasing leadership exemplars to propel professional practice model
      implementation.
AB  - Implementing a professional practice model is a highly complex organizational
      change that requires expert leadership to be successful. What are the aspects of
      successful leadership in implementing such a practice change, and how can those
      behaviors be transferred to other leaders? The authors describe qualitative
      research that examined this question by interviewing key leaders who are seen by
      peers as exemplifying the components and intent of one professional practice
      model. Using their responses to educate peers is seen as a method to expand their
      best practices. The authors recommend methods to disseminate these best practices
      in other organizations.

PMID- 18327063
TI  - Hospital-based palliative care: cost-effective care for patients with advanced
      disease.
AB  - Palliative care programs in acute care facilities provide a safety net for
      patients with advanced disease. While providing aggressive symptom management for
      patients, these programs are also cost-effective. This author discusses the
      economic advantages of improving care for patients with advanced disease.

PMID- 18327064
TI  - Spreading nursing unit innovation in large hospital systems.
AB  - Healthcare administrators increasingly face the challenge of how to spread
      innovation throughout their organizations. The authors present the results of an
      evaluation of the efforts of 3 major hospital systems to internally disseminate
      nursing unit change among medical-surgical units. The findings show that all 3
      organizations carefully planned, coordinated, and implemented a spread process;
      none left dissemination to chance. Although clear differences were evident in the
      way they engineered their spread, many similarities also were found.

PMID- 18327065
TI  - Primary aldosteronism: an update on screening, diagnosis and treatment.
AB  - BACKGROUND: Primary aldosteronism is much more common than previously held; it
      implies an excessive organ damage to the heart, vessels and kidney, which
      translates into an excess of cardiovascular events. These two features, along
      with the fact that the arterial hypertension and the hypokalemia can be corrected
      with a timely diagnosis and an appropriate therapy, warrant an aggressive
      diagnostic approach in hypertensive patients. OBJECTIVES: To provide updated
      information on the screening and exclusion tests for primary aldosteronism and to
      illustrate the strategy that can be followed for primary aldosteronism subtype
      differentiation. DESIGN: Review of the literature and personal experience of the
      authors. RESULTS: The available evidence showed that a cost-effective strategy
      for the screening of patients with primary aldosteronism can be exploited at most
      centres. At variance, the identification of primary aldosteronism subtypes, for
      example, the differentiation of patients with an aldosterone-producing adenoma
      from those with idiopathic hyperaldosteronism should be undertaken at tertiary
      referral centres. CONCLUSION: The identification of a curable form of primary
      aldosteronism can be much rewarding for the patient and the doctor. Thus, an
      aggressive diagnostic approach is mandatory at least in some subgroups of
      hypertensive patients who are at higher prior risk of primary aldosteronism or
      can benefit more from an accurate diagnosis.

PMID- 18327066
TI  - Antihypertensive medication and their impact on cancer incidence: a mixed
      treatment comparison meta-analysis of randomized controlled trials.
AB  - OBJECTIVE: The aim of this article is to determine the association between
      commonly used antihypertensive agents and the incidence of cancer. METHODS: We
      conducted a mixed treatment comparison meta-analysis of randomized, controlled
      (placebo, active, or untreated control) trials of antihypertensive drugs. A
      systematic literature search was conducted through June 2007. The primary outcome
      measure assessed was the incidence of cancer. Mixed treatment comparison meta
      analysis was used to combine direct, within-trial, and between-drug comparisons
      with indirect evidence from the other trials. The indirect comparisons, which
      safeguard within-trial randomized findings, were constructed from trials with one
      treatment in common. Results are reported as odds ratios with 95% credible
      intervals. RESULTS: In total, 27 studies (56 treatment arms, 126137 patients
      enrolled, and 5868 cancers identified during follow-up) were included in the base
      case analysis. They were hypertension, prehypertension, heart failure, coronary
      artery disease, or renal disease trials and patients were randomized to one of
      the five major antihypertensive drug classes or to placebo/untreated control.
      With the placebo/untreated control group as the referent comparison, the odds for
      developing cancer were 0.99 (0.80-1.24) for angiotensin-converting enzyme
      inhibitors; 1.12 (0.87-1.47) for angiotensin receptor blockers; 1.00 (0.78-1.32)
      for beta-adrenergic blockers; 0.94 (0.73-1.19) for diuretics and 0.95 (0.79-1.13)
      for calcium channel blockers. In sensitivity analyses, the results were not
      altered to any noteworthy extent including exclusion of studies under 3 years
      duration. CONCLUSION: Based on the totality of the clinical trial literature,
      commonly used antihypertensive drugs are not associated with increased odds of
      developing cancer.

PMID- 18327067
TI  - Optimizing the definition of dippers and nondippers: is a 70-86% full glass
      empty?

PMID- 18327068
TI  - Is albuminuria a marker of arterial remodeling?

PMID- 18327069
TI  - Pulmonary venous flow: adding prognostic significance to diastolic dysfunction.

PMID- 18327070
TI  - Beyond baseline data: the use of time-varying covariates.

PMID- 18327071
TI  - Health-related quality of life and hypertension status, awareness, treatment, and
      control: National Health and Nutrition Examination Survey, 2001--2004.
AB  - OBJECTIVE: We examined health-related quality of life measures by hypertension
      status, awareness, treatment, and control. METHODS: Five unfavorable health
      related quality of life measures were analyzed among 8303 adults aged 20 years or
      older who participated in the 2001--2004 National Health and Nutrition
      Examination Survey. Multivariable logistic regression analyses examined
      differences in health-related quality of life with adjustment for age, race, sex,
      healthcare coverage, and other medical conditions. RESULTS: The 30% of
      respondents with hypertension were more likely to report fair or poor health
      status (adjusted odds ratio 1.72, 95% confidence interval 1.44-2.05), 14 or more
      unhealthy days in the past 30 days (1.23, 1.06-1.43), 14 or more physically
      unhealthy days (1.39, 1.15-1.67), and 14 or more activity-limited days (1.55,
      1.17-2.04) than those without hypertension. Among adults with hypertension, the
      73.2% who were aware of their condition were more likely to report fair or poor
      health status (2.19, 1.54-3.12), 14 or more unhealthy days (1.53, 1.12-2.09), 14
      or more physically unhealthy days (1.49, 1.10-2.03), 14 or more mentally
      unhealthy days (1.70, 1.05-2.75), and 14 or more activity-limited days (2.38,
      1.39-4.05) than those who were unaware. Among those aware they had hypertension,
      14 or more physically unhealthy days (0.50, 0.28-0.90) was associated with
      current treatment. Health-related quality of life measures did not differ by
      blood pressure control status. CONCLUSIONS: Having hypertension and being aware
      of it was related to lower health-related quality of life. Antihypertensive
      medication was associated with more physically unhealthy days, while there were
      no differences in health-related quality of life by control status. Further study
      is needed to examine these differences including: disease severity, sex and
      racial/ethnic differences, comorbidities not examined, and impact of health
      related quality of life and its changes on outcomes.

PMID- 18327072
TI  - How Ghanaian, African-Surinamese and Dutch patients perceive and manage
      antihypertensive drug treatment: a qualitative study.
AB  - OBJECTIVES: To explore and compare how Ghanaian, African-Surinamese (Surinamese),
      and White-Dutch patients perceive and manage antihypertensive drug treatment in
      Amsterdam, the Netherlands. METHODS: Qualitative study was conducted using
      detailed interviews with a purposive sample of 46 hypertensive patients without
      comorbidity who were prescribed antihypertensives. RESULTS: Patients in all the
      ethnic groups actively decided how to manage their prescribed antihypertensive
      regimens. In all the groups, confidence in the doctor and beneficial effects of
      medication were reasons for taking prescribed antihypertensive dosage.
      Particularly, ethnic-minority patients reported lowering or leaving off the
      prescribed medication dosage. Explanations for altering prescribed dosage
      comprised disliking chemical medications, fear of side effects and preference for
      alternative treatment. Surinamese and Ghanaian men also worried about the
      negative effects of antihypertensives on their sexual performance. Some Ghanaians
      mentioned fear of addiction or lack of money as explanations for altering
      prescribed dosage. Surinamese and Ghanaians often discontinued medication when
      visiting their homeland. Some respondents from all ethnic groups preferred
      natural treatments although treatment type varied. CONCLUSION: Patients'
      explanations for their decisions regarding the use of antihypertensives are often
      influenced by sociocultural issues and in ethnic-minority groups also by
      migration-related issues. Self-alteration of prescribed medication among
      Surinamese and Ghanaians may contribute to the low blood pressure (BP) control
      rate and high rate of malignant hypertension reported among these populations in
      the Netherlands. This study provides new information, which can help clinicians
      to understand how patients of diverse ethnic populations think about managing
      antihypertensive drug treatment and to address ethnic disparities in medication
      adherence and BP control.

PMID- 18327073
TI  - Association between hypertensive urgencies and subsequent cardiovascular events
      in patients with hypertension.
AB  - OBJECTIVE: To determine whether patients with hypertensive urgency have a higher
      risk for subsequent cardiovascular events compared with hypertensive patients
      without this event. METHODS: Overall, 384 patients with hypertensive urgency and
      295 control patients were followed up for at least 2 years. Hypertensive urgency
      was defined as a systolic blood pressure above 220 mmHg and/or a diastolic blood
      pressure above 120 mmHg without any evidence of acute end-organ damage. The
      control group consisted of patients admitted to the emergency department with a
      systolic blood pressure between 135 to 180 mmHg and a diastolic blood pressure
      between 85-110 mmHg. The number of cardiovascular events defined as acute
      coronary syndrome, acute stroke, atrial fibrillation, acute left ventricular
      failure and aortic aneurysm were consecutively analyzed during follow-up. The
      median follow-up time was 4.2 years (interquartile range 2.9-5.7 years). Twenty
      six patients of the urgency group and 23 patients of the control group were lost
      for follow-up. RESULTS: Overall, 117 (17%) patients had nonfatal clinical
      cardiovascular events and 13 had (2%) fatal cardiovascular events. The frequency
      of cardiovascular events was significantly higher in patients with hypertensive
      urgencies (88 vs. 42; P = 0.005). The Cox regression analysis identified age (P <
      0.001) and hypertensive urgencies (P = 0.035) as independent predictors for
      subsequent cardiovascular events. CONCLUSIONS: Hypertensive urgencies are
      associated with an increased risk for subsequent cardiovascular events in
      patients with arterial hypertension.

PMID- 18327074
TI  - Risk factors associated with uncontrolled hypertension: findings from the
      baseline CARMEN survey in Cienfuegos, Cuba.
AB  - OBJECTIVES: Identifying methods to improve pharmacologic control of elevated
      blood pressure remains the most urgent challenge in clinical research on
      hypertension. The probability of having inadequate control varies widely in the
      population and better understanding of the factors responsible could help to
      focus treatment strategies. METHODS: A population-based community survey of 1475
      persons aged 25-74 years, in Cienfuegos, Cuba, was used to identify these factors
      in a low-resource setting. RESULTS: While half of women with hypertension were
      controlled, only one-third of men were receiving successful treatment. Gender
      differences were not seen, however, among those currently taking medications. The
      largest burden of hypertension in absolute terms was concentrated in the age
      range 45-64, emphasizing the heavy burden of uncontrolled high blood pressure
      that falls on middle-aged men. Race-ethnicity was not a determinant of treatment
      and control status, nor was inability to obtain medication. CONCLUSIONS: These
      findings largely confirm the pattern observed in industrialized countries and
      demonstrate the near-universal challenge confronting primary-care systems in
      physician-based control of cardiovascular risk factors.

PMID- 18327075
TI  - Making hypertensive smokers motivated in quitting: developing 'blood pressure
      equivalence of smoking'.
AB  - OBJECTIVE: To express the increased risk from smoking in terms of 'blood
      pressure' so that hypertensive smokers are motivated into quitting. METHODS:
      Mortality risks of smokers were compared with nonsmokers in a large worker cohort
      in Taiwan (n = 23755 with a 17-year follow-up) for all-cause and for
      cardiovascular diseases. The blood pressure equivalence of smoking was then
      identified by the difference in mortality risks between smokers and nonsmokers.
      RESULTS: Some interaction between hypertension and smoking was found to be
      synergistic. When hypertension and smoking co-existed, the all-cause mortality
      outcome [relative risk (RR) = 4.25] was larger than the sum or product of each
      individual risk for hypertension (RR = 2.16) or for smoking (RR = 1.97). The
      excess mortality risks of smoking for smokers were converted into a 'blood
      pressure equivalence'. The results demonstrate that the addition of smoking was
      similar to an increase of mortality risk approximately equivalent to an increase
      in blood pressure of 40 mmHg. CONCLUSIONS: Smoking cessation in hypertensive
      patients could provide a reduction of mortality risks similar to a permanent
      reduction of 40 mmHg in blood pressure, over and above any antihypertensive
      medications. Appreciating this relationship enables physicians to bridge the
      clinical disconnection and motivates hypertensive smokers to seek smoking
      cessation. The use of a 'blood pressure equivalence of smoking' can link the two
      separate risk factors and may lead to a paradigm shift in overcoming an existing
      clinical challenge.

PMID- 18327076
TI  - Oscillometrically measured blood pressure in Hong Kong Chinese children and
      associations with anthropometric parameters.
AB  - BACKGROUND: Oscillometric devices are increasingly used to measure blood pressure
      (BP). Reference data are limited and have not used devices validated against
      sphygmomanometric measurements on which current standards are based. BP standards
      for Chinese children have been based on sphygmomanometry and have not provided
      height-related or weight-related BP percentiles. METHODS: BP was measured in
      14842 Hong Kong Chinese schoolchildren aged 6-18 years randomly selected from 36
      schools in the 18 Hong Kong districts, using a validated oscillometric device
      (Datascope Accutorr Plus). Height, weight, heart rate and waist circumference
      were measured. Percentiles for systolic BP and diastolic BP by sex, age, height
      and weight were generated. Features associated with systolic BP and diastolic BP
      in 12680 children were analysed by univariate and multivariate analysis. RESULTS:
      Reference BP standards by sex, age, weight and height are presented. BP was
      associated (in descending order of strength) with weight > height > age > waist
      circumference > body mass index, and weakly with heart rate (which added
      considerable influence on multivariate analysis). BP increases similarly with
      age, height (which can normalize for variations in growth) and weight (which is
      associated most strongly with BP). BP was associated also with family history of
      high BP and (inversely) with sleep duration. CONCLUSIONS: The study provides
      oscillometrically measured BP standards for Chinese children, with age-related
      and sex-related height-specific and weight-specific percentiles. Implications of
      the findings are discussed. Screening by sex-specific BP-height percentile
      charts, and then if high, reference to the BP-sex-age-weight table, is suggested.

PMID- 18327077
TI  - Cost-effectiveness of the introduction of home blood pressure measurement in
      patients with office hypertension.
AB  - OBJECTIVE: Cost-effectiveness of hypertension treatment is an important social
      and medical issue in Western as well as in Eastern countries, including Japan.
      Home blood pressure (HBP) measurements have a stronger predictive power for
      cardiovascular events than casual clinic blood pressure (CBP) measurements.
      Therefore, the introduction of HBP measurement for the diagnosis and treatment of
      hypertension should lead to a decrease in medical expenditure. This study
      presents calculations of the cost savings likely to take place when HBP is
      implemented for newly detected hypertensive subjects in Japan. DESIGN AND
      METHODS: We estimate the cost savings from the perspective of a Japanese
      healthcare system. To estimate the costs associated with changing from CBP to HBP
      measurement as the diagnostic tool, we constructed a simulation model using data
      from the Ohasama study. These calculations are based on current estimates for
      cost of treatment, prevalence of white-coat hypertension at baseline, and varying
      the incidence of new hypertension after the initial screening. RESULTS: When HBP
      measurement is not incorporated into the diagnostic process, the medical cost is
      estimated at US$10.89 million per 1000 subjects per 5 years. When HBP measurement
      is incorporated, the medical cost is estimated at US$9.33 million per 1000
      subjects per 5 years. The reductions in medical costs vary from US$674,000 to
      US$2.51 million per 1000 subjects per 5 years for treatment of hypertension, when
      sensitivity analysis is performed. CONCLUSIONS: The introduction of HBP
      measurement for the treatment of hypertension is very useful for reducing medical
      costs.

PMID- 18327078
TI  - Different classifications of nocturnal blood pressure dipping affect the
      prevalence of dippers and nondippers and the relation with target-organ damage.
AB  - OBJECTIVE: We assessed how different definitions of the awake and asleep periods
      and use of various blood pressure (BP) indices affect the extent of the nocturnal
      BP dip, the prevalence of dippers and nondippers, their respective
      reproducibilities and the relation of nondipping with target-organ damage.
      METHODS: We performed 24-h ambulatory BP monitoring twice and determined the left
      ventricular mass index and urinary albumin excretion as indices of target-organ
      damage in 150 hypertensive patients (off-medication). Awake and asleep periods
      were assessed using fixed and diary time methods, covering all readings available
      (wide) or excluding morning and evening transition hours (narrow). Nondipping (BP
      dip < 10%) was established for systolic BP and diastolic BP, their combinations
      (and/or), and mean arterial pressure. RESULTS: The different awake-asleep
      definitions caused significant variation in both the extent of the BP dip and the
      number of dippers and nondippers in comparison with the wide diary definition
      (i.e. use of actual awake and sleep periods). The prevalences of dippers and
      nondippers also varied significantly with the BP index. Reproducibility analyses
      of the BP dip and the dipping status yielded repeatability coefficients
      (expressed as percentages of nearly maximal variation) between 42.39 and 48.71%,
      and kappa values between 0.323 and 0.459, respectively. Some classifications, but
      not all, discriminated significantly between consistent dippers and nondippers in
      terms of left ventricular mass index or urinary albumin excretion. CONCLUSIONS:
      Use of different definitions of awake-asleep and BP indices affects significantly
      the classification of nocturnal BP dipping and its relation with hypertensive
      target-organ damage.

PMID- 18327079
TI  - The white coat phenomenon is benign in referred treated patients: a 14-year
      ambulatory blood pressure mortality study.
AB  - OBJECTIVE: Previous reports on the prognosis of white coat hypertension are
      ambiguous. We aimed to determine the prognostic implications of the white coat
      phenomenon in treated patients. METHODS: Our 14-year hospital-based ambulatory
      blood pressure (BP) monitoring prospective database was analyzed for all-cause
      mortality. The relationships of the white coat and masking effects with mortality
      were assessed both categorically (controlled awake versus clinic BP) and in a
      continuous mode (clinic-awake BP difference). RESULTS: During the follow-up
      period, 2285 treated patients (aged 61 +/- 13 years, 57% women) were monitored
      (17621 patient-years, 286 deaths). Mean BMI was 27.8 +/- 4.5 kg/m2 and 13% were
      treated for diabetes. Controlled hypertension (normal clinic and awake BP) was
      found in 15.8%, high clinic BP (with controlled awake BP; namely, white coat
      uncontrolled hypertension) in 12.1%, awake hypertension (with controlled clinic
      BP; namely, masked uncontrolled hypertension) in 11.8%, and sustained
      hypertension (both clinic and awake) in 60.3%. Compared with white coat
      uncontrolled hypertension, age-adjusted Cox-proportional all-cause mortality
      hazard ratios were 1.42 (0.81-2.51) for controlled hypertension, 1.88 (1.08-3.27)
      for masked uncontrolled hypertension, and 2.02 (1.30-3.13) for sustained
      hypertension. Hazards ratios per 1% increase in the clinic-awake BP difference
      were 0.992 (0.983-1.002) for systolic BP and 0.981 (0.971-0.991) for diastolic
      BP, adjusted for age, sex, diabetes, and either systolic or diastolic awake BP,
      respectively. CONCLUSION: In treated hypertensive patients referred for
      ambulatory BP monitoring, the white coat effect is benign compared with the
      reverse (masking) phenomenon, which has a poorer prognosis.

PMID- 18327080
TI  - Different contributions of the angiotensin-converting enzyme C-domain and N
      domain in subjects with the angiotensin-converting enzyme II and DD genotype.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) insertion/deletion (I/D)
      polymorphism-related differences in ACE concentration do not result in
      differences in angiotensin levels. METHODS AND RESULTS: To investigate whether
      this relates to differences in the contribution of the ACE C-domain and N-domain,
      we quantified, using the C-domain-selective inhibitors quinaprilat and RXPA380,
      and the N-domain-selective inhibitor RXP407, the contribution of both domains to
      the metabolism of angiotensin I, bradykinin, the C-domain-selective substrate Mca
      BK(1-8), and the N-domain-selective substrate Mca-Ala in serum of IIs, DDs, and
      'hyperACE' subjects (i.e., subjects with increased ACE due to enhanced shedding).
      During incubation with angiotensin I, the highest angiotensin II levels were
      observed in sera with the highest ACE activity. This confirms that ACE is rate
      limiting with regard to angiotensin II generation. C-domain-selective
      concentrations of quinaprilat fully blocked angiotensin I-II conversion in DDs,
      whereas additional N-domain blockade was required to fully block conversion in
      IIs. Both domains contributed to bradykinin hydrolysis in all subjects, and the
      inhibition profile of RXP407 when using Mca-Ala was identical in IIs and DDs. In
      contrast, the RXPA380 concentrations required to block C-domain activity when
      using Mca-BK (1-8) were three-fold higher in IIs than DDs. CONCLUSION: The
      contributions of the C-domain and N-domain differ between DDs and IIs, and
      RXPA380 is the first inhibitor capable of distinguishing D-allele ACE from I
      allele ACE. The lack of angiotensin II accumulation in DDs in vivo is not because
      of the often quoted concept that ACE is a nonrate-limiting enzyme. It may relate
      to the fact that in IIs both the N-domain and C- domain generate angiotensin II,
      whereas in DDs only the C-domain converts angiotensin I.

PMID- 18327081
TI  - Genetic and dietary control of plasma tissue kallikrein secretion and urinary
      kinins exretion in man.
AB  - OBJECTIVES: Tissue kallikrein is a major kinin-forming enzyme involved in artery
      and kidney functions. Urinary tissue kallikrein activity (UKLKa) reflects renal
      tissue kallikrein activity and depends on Na and K intake, and genetic factors,
      especially the tissue kallikrein-inactivating polymorphism, R53H. The effect of
      these factors on the level of kinin peptides is, however, not known. Moreover, a
      circulating form of tissue kallikrein is present in human plasma but its origin
      and regulation are unknown. METHODS: We used a crossover study to investigate
      UKLKa, plasma tissue kallikrein (pTK), and urinary kallidin peptides and
      metabolites (Uki) in 10 R53H and 30 R53R normotensive male subjects randomly
      assigned to either a 1-week low Na-high K or a high Na-low K diet. RESULTS: UKLKa
      was 50-60% lower in R53H than R53R subjects and was increased by the low Na-high
      K diet. pTK was also 45-55% lower in R53H than R53R subjects and was increased by
      the low Na-high K diet. Uki was slightly but significantly higher under the low
      Na-high K than the high Na-low K diet, but did not differ between genotypes.
      CONCLUSION: These observations indicate that pTK levels are genetically
      determined and regulated by Na and K diet, in parallel with UKLKa; this suggests
      that circulating tissue kallikrein originates mainly from the kidney, and can
      contribute to circulatory adaptation to dietary ions. Uki is influenced by the Na
      and K diet, suggesting that kinins participate in renal adaptation to ion intake,
      but do not quantitatively reflect tissue kallikrein activity in urine, or
      presumably, in the kidney.

PMID- 18327082
TI  - Heritability and intrafamilial aggregation of arterial characteristics.
AB  - BACKGROUND: We investigated the heritability and familial aggregation of various
      indexes of arterial stiffness and wave reflection and we partitioned the
      phenotypic correlation between these traits into shared genetic and environmental
      components. METHODS: Using a family-based population sample, we recruited 204
      parents (mean age, 51.7 years) and 290 offspring (29.4 years) from the population
      in Cracow, Poland (62 families), Hechtel-Eksel, Belgium (36), and Pilsen, the
      Czech Republic (50). We measured peripheral pulse pressure (PPp)
      sphygmomanometrically at the brachial artery; central pulse pressure (PPc), the
      peripheral augmentation indexes (PAIxs) and central augmentation indexes (CAIxs)
      by applanation tonometry at the radial artery; and aortic pulse wave velocity
      (PWV) by tonometry or ultrasound. In multivariate-adjusted analyses, we used the
      ASSOC and PROC GENMOD procedures as implemented in SAGE and SAS, respectively.
      RESULTS: We found significant heritability for PAIx, CAIx, PPc and mean arterial
      pressure ranging from 0.37 to 0.41; P < or = 0.0001. The method of intrafamilial
      concordance confirmed these results; intrafamilial correlation coefficients were
      significant for all arterial indexes (r > or = 0.12; P < or = 0.02) with the
      exception of PPc (r = -0.007; P = 0.90) in parent-offspring pairs. The sib-sib
      correlations were also significant for CAIx (r = 0.22; P = 0.001). The genetic
      correlation between PWV and the other arterial indexes were significant (rhoG >
      or = 0.29; P < 0.0001). The corresponding environmental correlations were only
      significantly positive for PPp (rhoE = 0.10, P = 0.03). CONCLUSION: The
      observation of significant intrafamilial concordance and heritability of various
      indexes of arterial stiffness as well as the genetic correlations among arterial
      phenotypes strongly support the search for shared genetic determinants underlying
      these traits.

PMID- 18327083
TI  - Genetic influences on blood pressure response to the cold pressor test: results
      from the Heredity and Phenotype Intervention Heart Study.
AB  - OBJECTIVES: Blood pressure (BP) response to the cold pressor test (CPT) has been
      found to predict the development of hypertension and cardiovascular disease in
      prospective studies. The determinants of BP response to the CPT, including the
      role of genetic factors, however, are largely unknown. Additionally, to our
      knowledge, no study has examined the genetics of BP recovery from the CPT,
      including whether shared genetic factors influence both reactivity and recovery.
      METHODS: As part of the Heredity and Phenotype Intervention Heart Study, we
      administered a 2.5 min hand CPT to 835 participants from 18 extended Amish
      families. We estimated the heritability of BP reactivity and recovery (measured
      by the incremental area under the curve) and the genetic correlations between
      baseline, reactivity, and recovery BP phenotypes. RESULTS: After adjusting for
      relevant covariates, including baseline BP, the heritability estimates for both
      systolic BP (SBP) and diastolic BP (DBP) reactivity and recovery differed
      significantly from zero (P < 0.01), with 12-25% of the total variation in BP
      response attributable to additive genetic effects. The genetic correlations
      between baseline DBP and response phenotypes were not significantly different
      from zero, whereas the genetic correlation between DBP reactivity and recovery
      (0.74) was significantly different from zero and 1 (P < 0.005). The genetic
      correlation between SBP reactivity and recovery was similar (0.81; P < 0.05).
      CONCLUSION: We conclude that, independent of baseline BP, BP response to CPT is
      heritable, and that both shared and unshared genetic factors influence BP
      reactivity and recovery, thus stressing the importance of identifying genetic
      variants that influence both traits.

PMID- 18327084
TI  - Nifedipine improves the migratory ability of circulating endothelial progenitor
      cells depending on manganese superoxide dismutase upregulation.
AB  - BACKGROUND: Migratory ability of resident endothelial cells and their circulating
      progenitors, that is endothelial progenitor cells (EPCs), represent a crucial
      event in vascular repairing processes. Although oxidants are known to counteract
      the migratory ability of resident endothelial cells, their possible role in
      modulating EPC motility is unknown. EPCs exhibit stronger resistance to oxidants
      than mature endothelial cells mainly because of higher expression of manganese
      (Mn) superoxide dismutase (SOD). As nifedipine is a dihydropyridine calcium
      antagonist known to enhance MnSOD expression in mature endothelial cells, we
      investigated the effects of nifedipine on MnSOD expression and motility in EPCs.
      METHODS AND RESULTS: EPCs were isolated from peripheral blood of healthy donors
      and cultured in fibronectin-coated flasks. Nifedipine improved both motility of
      cultured EPCs (+55% vs. control, P = 0.007) and their adhesion to tumor necrosis
      factor-alpha-activated mature endothelial cells (+33% vs. control, P = 0.03).
      Reduction of EPC dichlorofluorescein content (-32% vs. control, P = 0.009) and a
      parallel increase in nitrite plus nitrate concentration in EPC supernatants (+25%
      vs. control, P = 0.009) were also observed. The study of SOD showed a nifedipine
      dependent upregulation of MnSOD in a time-dependent and dose-dependent manner.
      MnSOD expression blockade by RNA interference abolished nifedipine effect on EPC
      motility. Although nifedipine also increased vascular endothelial growth factor
      (VEGF) release from EPCs, its effect on EPC motility was unaffected by an anti
      VEGF antibody. CONCLUSION: Nifedipine improves EPC motility due to MnSOD
      upregulation. The capability of this dihydropyridine calcium antagonist to reduce
      cardiovascular events might also be related to improved EPC function.

PMID- 18327085
TI  - Accelerated arterial stiffening and gene expression profile of the aorta in
      patients with coronary artery disease.
AB  - BACKGROUND: Hypertension and chronic renal failure (CRF) are considered models of
      accelerated arterial stiffening. Arterial stiffness increases further when CRF is
      associated with hypertension. We hypothesized that, in patients with mild CRF,
      aortic gene expression profile would include genes involved in arterial
      calcifications and enlargement. METHOD: We analysed human aorta with the
      'GeneChip Microarray' technology, in patients with or without CRF, scheduled for
      a coronary artery bypass graft. RESULTS: Nine of 25 patients had high-quality RNA
      and were included in the study. Among the 101 transcripts differentially
      expressed between CRF patients and controls, 97 transcripts were overexpressed in
      CRF patients. Two genes had the highest overexpression in CRF patients: lumican
      (LUM), involved in the regulation of collagen fibrillogenesis; and ornithine
      decarboxylase (ODC1), involved in polyamine biosynthesis, smooth muscle cell
      growth and proliferation. Immunohistochemical staining revealed an increased
      amount of LUM and ODC1 in the vascular smooth muscle cells (VSMCs) of CRF
      compared to non-CRF aortic sections. Eight genes were implicated in the
      regulation of the cytoskeleton (including capping protein muscle Z-line 1 alpha
      and moesin) and cell migration, and five genes were implicated in extracellular
      matrix function and apoptosis. A trend towards an upregulation of candidate genes
      involved in arterial calcifications was observed in CRF patients, but did not
      reach statistical significance. Carotid-femoral pulse wave velocity was not
      correlated with gene expression level. CONCLUSION: In conclusion, these results
      show that patients at an early stage of CRF have a specific gene expression
      profile of aortic tissue and suggest that genes implicated in collagen
      fibrillogenesis, and VSMCs migration and proliferation, particularly LUM and
      ODC1, may play a role.

PMID- 18327086
TI  - Aortic stiffness for the detection of preclinical left ventricular diastolic
      dysfunction: pulse wave velocity versus pulse pressure.
AB  - OBJECTIVE: An age-dependent relationship between aortic and left ventricular (LV)
      stiffening has been observed in community-based adults. Our aim was to compare
      the performances of wave reflection-dependent (pulse pressure) and independent
      [carotid-femoral pulse wave velocity (PWV)] indexes of aortic stiffness to detect
      preclinical LV diastolic dysfunction. METHODS: In this case-control study, a
      stratified subsample of participants of a population-based echocardiographic
      survey with LV ejection fraction higher than 45% and without overt heart failure
      was randomly selected to undergo assessment of brachial blood pressure, LV
      diastolic function by Doppler echocardiography, and estimation of central aortic
      pressures and PWV by applanation tonometry. RESULTS: Of the 233 subjects (mean
      age 73 +/- 6 years, 54% men), 84 had normal diastolic function, 99 had mild
      diastolic dysfunction, and 50 had moderate or severe diastolic dysfunction.
      Brachial pulse pressure, central pulse pressure, and PWV progressively increased
      according to the severity of diastolic dysfunction, independent of age and sex.
      The overall performance of PWV was superior to brachial pulse pressure [area
      under receiver operating characteristic curve (AUC): 0.70 versus 0.59,
      respectively; P = 0.005] and central pulse pressure (AUC: 0.70 versus 0.56,
      respectively; P = 0.001) for the detection of any diastolic dysfunction.
      CONCLUSION: PWV appeared to be superior to central and brachial pulse pressure
      for the detection of diastolic dysfunction in older adults with 'preserved' LV
      ejection fraction.

PMID- 18327087
TI  - Attenuation of hypertension development by scavenging methylglyoxal in fructose
      treated rats.
AB  - OBJECTIVES: Methylglyoxal is a reactive dicarbonyl intermediate of metabolism
      produced in the body. It reacts with certain proteins and forms damaging advanced
      glycation endproducts (AGEs) such as N epsilon-carboxyethyl-lysine (CEL) and N
      epsilon-carboxymethyl-lysine (CML). Increased methylglyoxal levels are found in
      diabetes mellitus and associated with hypertension development in the
      spontaneously hypertensive rats (SHR). The purpose of this study was to
      investigate whether increased endogenous formation of methylglyoxal and
      methylglyoxal-induced AGEs caused hypertension development in normotensive
      Sprague Dawley rats. METHODS: The rats were fed chronically for 16 weeks with
      fructose, a known precursor of methylglyoxal formation. One group of rats was
      cotreated with fructose and metformin, an AGEs formation inhibitor. Methylglyoxal
      and reduced glutathione (GSH) were measured by high performance liquid
      chromatography, whereas hydrogen peroxide was measured by a dicholorofluorescin
      assay. Immunohistochemistry was performed for endothelial nitric oxide synthase
      (eNOS), CEL and CML. RESULTS: Fructose-fed rats had elevated blood pressure,
      serum methylglyoxal and triglycerides and reduced serum levels of GSH.
      Methylglyoxal, hydrogen peroxide and CEL were increased in the aorta, whereas
      eNOS was reduced. CEL and CML were also increased in the mesenteric artery
      endothelium along with media/lumen ratio, signifying structural remodelling. All
      the harmful changes in fructose-fed rats were attenuated in metformin and
      fructose cotreated rats. CONCLUSION: Increased methylglyoxal, AGEs, oxidative
      stress and reduced eNOS along with structural remodeling of the vessel wall in
      the aorta and mesenteric artery likely play a role in the pathogenesis of
      hypertension.

PMID- 18327088
TI  - Evidence for no global effect of metabolic syndrome per se on early hypertensive
      sequelae.
AB  - OBJECTIVE: In the present study we assessed the impact of metabolic syndrome (MS)
      and its components on markers of cardiovascular and renal damage in a population
      of essential hypertensives. METHODS: A total of 651 consecutive, untreated and
      non-diabetic hypertensives (age 54 +/- 12 years, 340 males) who were included in
      the 3H Study, an ongoing registry of hypertension-related target organ damage,
      were considered for analysis. Left ventricular mass was indexed both for body
      surface area (LVMBSA) and for height2.7 (LVMheight2.7). Diastolic function was
      estimated by means of both conventional and tissue Doppler imaging (TDI) methods.
      Arterial stiffness was evaluated on the basis of carotid to femoral pulse wave
      velocity (c-f PWV) and microalbuminuria (MA) as albumin to creatinine ratio (ACR)
      22-300 mg/g in men and 31-300 mg/g in women in two non-consecutive morning spot
      urine samples. RESULTS: MS (Adult Treatment Panel III criteria) was present in
      201 hypertensives (30.9%). Hypertensives with MS had increased logACR (by 10%, P
      = 0.01) and higher prevalence of MA (17 versus 8%, P < 0.001). Both groups
      exhibited similar values of LVMBSA, transmitral and TDI-derived indexes and c-f
      PWV (NS for all) while LVMheight2.7 was significantly higher in hypertensives
      with MS (by 2.6 g/m2.7, P = 0.023). Multiple regression analysis revealed that MS
      was an independent predictor only of logACR (beta = 0.110, P = 0.007) and MA
      (odds ratio = 2.577, P < 0.001), while components of blood pressure affected all
      studied indices of organ damage. CONCLUSIONS: MS per se does not deteriorate
      cardiac adaptations and aortic stiffness beyond haemodynamic load in
      hypertension. The MS-related unfavourable effect is limited to the level of the
      glomerulus.

PMID- 18327089
TI  - The renin-angiotensin system contributes to renal fibrosis through regulation of
      fibrocytes.
AB  - BACKGROUND: The renin-angiotensin system is a major pathway in the pathogenesis
      of cardiovascular and renal diseases. Bone marrow-derived fibrocytes, which are
      dual positive for CD45 and type I collagen, are now considered to contribute to
      the pathogenesis of various fibrotic diseases. We hypothesized that fibrocytes
      might contribute to renal fibrosis by an angiotensin II dependent pathway.
      RESULTS: In murine models of renal fibrosis, angiotensin II type 2 receptor
      (AT2R)-deficient mice, when compared with wild-type mice, showed increased renal
      fibrosis and fibrocyte infiltration with a concomitant upregulation of renal
      transcripts of procollagen type I (alpha) (COL1A1). Fibrocyte numbers in the bone
      marrow also were increased in AT2R-deficient mice. By contrast, pharmacological
      inhibition of angiotensin II type 1 receptor (AT1R) with valsartan reduced the
      degree of renal fibrosis and the number of fibrocytes in both the kidney and the
      bone marrow. In isolated human fibrocytes, inhibition of AT2R signaling increased
      the angiotensin II-stimulated expression of type I collagen, whereas inhibition
      of AT1R decreased collagen synthesis. These results suggest that AT1R/AT2R
      signaling may contribute to the pathogenesis of renal fibrosis by at least two
      mechanisms: by regulating the number of fibrocytes in the bone marrow, and by
      activation of fibrocytes.

PMID- 18327090
TI  - Albuminuria, but not estimated glomerular filtration rate, is associated with
      maladaptive arterial remodeling: the Hoorn Study.
AB  - OBJECTIVE: Arterial remodeling aims to maintain a constant circumferential wall
      stress (sigmac). A failing remodeling process is associated with stroke. Data on
      the relationship between chronic kidney disease and arterial remodeling are
      scarce. METHODS: We investigated the association between a lower glomerular
      filtration rate (GFR) and microalbuminuria with arterial remodeling of the common
      carotid artery (CCA) in a population-based study of 806 patients. CCA properties
      including intima-media thickness and interadventitial diameter (IAD) were
      assessed. Lumen diameter, circumferential wall tension (CWT), and circumferential
      wall stress (sigmac) were calculated. GFR was estimated (eGFR) by the
      Modification of Diet in Renal Disease formula. Albuminuria was expressed as
      urinary albumin/creatinine ratio. RESULTS: Mean eGFR was 60.3 (+/-10.8)
      ml/min/1.73 m2; median urinary albumin/creatinine ratio was 0.57 (range 0.10-26.6
      mg/mmol). After adjustment for age, sex, glucose tolerance status, and prevalent
      cardiovascular disease, eGFR was not independently associated with CCA
      properties. A greater urinary albumin/creatinine ratio (per quartile) was
      associated with a greater lumen diameter [regression coefficient beta with 95%
      confidence interval, 0.14 (0.08-0.20; P < 0.01)], IAD [0.15 (0.09-0.21; P <
      0.01)], CWT [0.95 (0.52-1.38; P < 0.01)], and sigmac [1.7 (0.5-2.9; P < 0.01)]
      but not with a greater IMT [0.01 (-0.002-0.02; P = 0.12)]. Additional adjustments
      for mean arterial pressure, pulse pressure, and eGFR did not change the results.
      CONCLUSION: Greater albuminuria is independently associated with an increase in
      lumen diameter and IAD of the CCA. In addition, greater albuminuria is associated
      with a maladaptive carotid remodeling process as shown by an increase in CWT and
      sigmac. These findings may explain, why microalbuminuria is associated with a
      greater risk of cardiovascular disease and especially stroke.

PMID- 18327091
TI  - Pulmonary venous flow and risk of cardiovascular disease in essential
      hypertension.
AB  - OBJECTIVE: The prognostic significance of the pulmonary venous flow in essential
      hypertensive patients was investigated. METHODS AND RESULTS: Doppler
      transthoracic echocardiograms were analyzed in 705 essential hypertensive
      subjects with no prior cardiovascular disease. At baseline, most subjects had
      'normal diastolic function' or 'mild diastolic dysfunction'. During follow-up
      (mean, 32 months), 56 participants developed cardiovascular disease. Sex-specific
      median values were used to separate the higher group from the lower group of the
      peak velocity ratio of the pulmonary venous systolic to diastolic wave (S/D)
      (male < 1.51, female < 1.66), and of the transmitral velocity ratio of early
      diastolic to atrial filling (E/A) (male < 0.84, female < 0.82). Kaplan-Meier
      curves with log-rank tests showed significantly poorer event-free survival rates
      in the groups with high S/D (P < 0.01) and low E/A (P < 0.01), respectively. In
      multivariate Cox regression analysis, the S/D ratio (HR 1.07 for each 0.1
      increase, P = 0.03) or E/A ratio (P < 0.01) was an independent predictor of
      cardiovascular disease events. When divided into four groups based on the
      respective sex-specific median levels of S/D in the E/A > or = median and E/A <
      median groups, the group with high S/D and low E/A (S/D; male > or = 1.77, female
      > or = 1.81) had a significantly poorer event-free survival rate (chi2 = 28.06, P
      < 0.01), and the adjusted-hazard ratio by multivariate Cox regression analysis
      was 2.16 (95% CI; 1.40-3.07, P < 0.01). CONCLUSION: Increased S/D or decreased
      E/A is associated with an increased cardiovascular disease risk, and the
      combination of high S/D and low E/A may be a powerful predictor of cardiovascular
      disease in essential hypertension. Pulmonary venous flow evaluation may provide
      clinically important prognostic information in patients with essential
      hypertension.

PMID- 18327092
TI  - Clinical impact of 'in-treatment' wall motion abnormalities in hypertensive
      patients with left ventricular hypertrophy: the LIFE study.
AB  - OBJECTIVES: Left ventricular systolic wall motion abnormalities have prognostic
      value. Whether wall motion detected by serial echocardiographic examinations
      predicts prognosis in hypertensive patients with left ventricular hypertrophy
      (LVH) without clinically recognized atherosclerotic disease has, however, never
      been investigated. We examined whether 'in-treatment' wall motion abnormalities
      predicted outcome in the Losartan Intervention For Endpoint (LIFE) reduction in
      hypertension echocardiographic substudy. METHODS: We studied 749 patients without
      coronary artery disease, myocardial infarction (MI), or stroke history.
      Echocardiographic segmental wall motion abnormalities at baseline and annual re
      evaluations ('as time-varying covariate') were examined in relation to endpoints
      (cardiovascular mortality, MI, stroke, and hospitalized heart failure). Adjusted
      Cox regression was used to analyze the primary composite endpoint of
      cardiovascular death, MI, or stroke and, separately, for fatal and nonfatal MI
      and hospitalized heart failure. RESULTS: During a mean follow-up of 4.8 years, an
      event was recorded in 67 (9%) patients. In Cox models after adjusting for age,
      gender, treatment, blood pressure lowering, and serial change of left ventricular
      mass index, 'in-treatment' segmental wall motion abnormalities were associated
      with subsequent composite endpoint [hazard ratio = 2.1, 95% confidence interval
      (CI) 1.1-3.8; P = 0.019] and MI [hazard ratio = 3.7 (1.5-8.9); P = 0.004].
      CONCLUSION: In hypertensive patients with LVH and no history of cardiovascular
      disease, 'in-treatment' left ventricular wall motion abnormalities are associated
      with increased likelihood of subsequent cardiovascular events independent of age,
      gender, blood pressure lowering, treatment modality, and in-treatment left
      ventricular mass index.

PMID- 18327093
TI  - Efficacy of manidipine/delapril versus losartan/hydrochlorothiazide fixed
      combinations in patients with hypertension and diabetes.
AB  - BACKGROUND: Hypertension markedly increases the already high risk for
      cardiovascular complications in patients with diabetes mellitus. Less than one in
      eight patients with hypertension and type 2 diabetes have adequately controlled
      blood pressure. As a result, antihypertensive combinations are now widely used in
      management of hypertension associated with diabetes. METHODS: This double-blind
      study investigated efficacy of a new fixed dose combination of a calcium
      antagonist, manidipine 10 mg, and an angiotensin-converting enzyme inhibitor,
      delapril 30 mg, compared with a combination of an angiotensin receptor blocker,
      losartan 50 mg, and a diuretic, hydrochlorothiazide 12.5 mg. Patients with
      hypertension (blood pressure > or = 130/80 mmHg) with controlled type 2 diabetes
      (HbA1c < or = 7.5%) were randomized to manidipine/delapril (n = 153) or
      losartan/hydrochlorothiazide (n = 161), administered once daily for 12 weeks.
      Patients underwent ambulatory blood pressure monitor evaluation at baseline and
      end of treatment. RESULTS: Mean decreases in 24-h systolic blood pressure were
      seen with both manidipine/delapril (-9.3 mmHg) and losartan/hydrochlorothiazide (
      10.7 mmHg) combinations. The mean (95% confidence interval) treatment difference
      was -1.4 (-4.5/1.8) mmHg, demonstrating noninferiority of the manidipine/delapril
      combination. Reduction in 24-h diastolic blood pressure (-4.6 versus -4.5 mmHg)
      and daytime (systolic blood pressure -10.5 versus -11.1 mmHg) and night-time
      (systolic blood pressure -7.1 versus -9.3 mmHg) blood pressure were also not
      significantly different between treatments. Compliance and adverse events were
      comparable for both groups. CONCLUSION: The study demonstrated that the
      combination of manidipine and delapril is as effective as losartan and
      hydrochlorothiazide in treatment of hypertension in type 2 diabetes.

PMID- 18327094
TI  - Discontinuation of and changes in drug therapy for hypertension among newly
      treated patients: a population-based study in Italy.
AB  - OBJECTIVES: To assess rates and determinants of treatment discontinuation of or
      changes in initial antihypertensive drug therapy in a large cohort of patients
      from Lombardia (Italy). METHODS: The cohort included 445356 patients aged 40 -80
      years who received their first antihypertensive drug prescription (monotherapy)
      during 1999--2002. Discontinuation was defined by the absence of any
      antihypertensive prescription during a 90-day period following the end of the
      latest prescription. If during the same period a drug of a different class was
      added or replaced the initial prescription, treatment modification was regarded
      as combination or switching, respectively. Competing risks methodology was used
      to estimate and compare cause-specific cumulative incidence. RESULTS: Cumulative
      incidences of discontinuation, combination and switching were respectively 33, 14
      and 15% at 6 months, 41, 18 and 17% at 1 year, and 50, 25 and 19% at 5 years
      since initial treatment. Compared with patients starting treatment with
      angiotensin-converting enzyme inhibitors, the rate of discontinuation was less
      for patients on angiotensin receptor blockers with a hazard ratio of 0.92 (95%
      confidence interval =0.90-0.94), whereas increased discontinuation was observed
      for patients starting with other drugs, mainly beta-blockers with a hazard ratio
      of 1.64 (1.62-1.67); and diuretics with a hazard ratio of 1.83 (1.81-1.85).
      CONCLUSION: In the general population of Lombardia, discontinuation of the
      initial single antihypertensive drug treatment is a common phenomenon, whereas
      switching to another monotherapy and to combination treatment occur at similarly
      much lower rates. Blockers of the renin-angiotensin system are associated with
      the lowest incidence of treatment discontinuation.

PMID- 18327095
TI  - The 2007 ESH/ESC guidelines for the management of arterial hypertension.

PMID- 18327098
TI  - Dipping in type II diabetes: autonomics and diuretics.

PMID- 18327099
TI  - Central vs. peripheral leptin excess in the pathogenesis of obesity-associated
      hypertension.

PMID- 18327100
TI  - Can we treat patients according to the latest hypertension trials?

PMID- 18327101
TI  - A new day for pediatric nurses.

PMID- 18327102
TI  - Should postpartum units be "formula free"?

PMID- 18327104
TI  - Induced lactation: gaining a better understanding.
AB  - Although a small minority in the United States, a number of adoptive mothers
      continue to seek information regarding the induction of lactation. Because of the
      level of support needed by these women to successfully induce lactation, it is
      necessary for nurses and other healthcare workers to gain a thorough
      understanding of the various processes and medications frequently used. Often,
      women who induce lactation cannot produce enough milk to exclusively breastfeed
      their infant but find satisfaction in this rigorous process because of the
      maternal-infant bonding it promotes. The adoptive mother seeking to induce
      lactation is a unique client in need of highly tailored and personalized care.

PMID- 18327106
TI  - Meeting the needs of the postpartum woman with epilepsy.
AB  - Although pregnancy and postpartum are times of emotional and physical change for
      all women, women with epilepsy have additional concerns and face special
      challenges. This article describes the nursing care for this special population
      to help the clinical nurse provide for the safety of these women and their
      infants. A multidisciplinary approach is essential, and families need to be
      included in the care planning. Special considerations for medication management,
      additional rest, seizure precautions, and discharge instructions are described.

PMID- 18327107
TI  - Preconception care & pregnancy planning: voices of African American women.
AB  - PURPOSE: This study aimed to investigate the intersection of women's pregnancy
      planning beliefs with preconception care barriers. We assessed the meaning of
      "planned pregnancy" for African American women and explored its connection to
      preconception experiences. The role of race and economics as contextualizing
      women's experiences was considered. STUDY DESIGN/METHODS: African American women
      (n = 168) recruited from health department sites discussed the following
      questions: "What does the term 'planned pregnancy' mean?" "Would you describe
      your most recent pregnancy as planned?" Substantive themes were extracted using
      phenomenological methodology. RESULTS: The following themes emerged: (1)
      Preconception care: An unfamiliar concept; (2) Planning for pregnancy: A
      continuum of responses; (3) The psychology of conception: Attitudes, beliefs, and
      behaviors; (4) The shared nature of pregnancy: It takes two to plan; (5) Birth
      control: The means to the end; and (6) The context of preconception care: The big
      picture. CLINICAL IMPLICATIONS: Nurses who care for women in the childbearing
      years should understand that planning for pregnancy is not a simple cognitive
      process, and that race and economics play a role in women's beliefs about
      pregnancy. Preconception care also encompasses the contexts of family, public
      health, and society. Linking preconception care with all medical encounters is an
      important but insufficient approach. Nurses should apply their understanding of
      the biopsychosocial dimensions of health in support of the goals of preconception
      healthcare. Holistic nursing and public health perspectives should be considered
      to broaden the scope of preconception interventions and more effectively address
      social factors that influence preconception care.

PMID- 18327108
TI  - Assisting pregnant women to prepare for disaster.
AB  - Disasters are natural or man-made life-altering events that require preplanning
      to save lives. Pregnant women are a particularly vulnerable population in such
      events, because they have special physical and psychosocial needs. Preparations
      made for labor and birth might have to be drastically altered in the event of an
      emergency, especially if a woman is separated from her familiar healthcare
      providers and facilities. The issue of breastfeeding also must be considered in
      disaster planning for pregnant women, along with occurrences such as food
      shortages and outbreak of illnesses caused by overcrowding of displaced persons.
      Recent events such as hurricane Katrina have demonstrated that maternal/child
      nurses need to become more aware of disaster planning and help to empower
      pregnant women with knowledge of how to handle their special needs in times of
      crisis.

PMID- 18327109
TI  - Understanding school-age obesity: through participatory action research.
AB  - PURPOSE: This study aimed to assess current levels of overweight (obesity) and
      fitness among school students using objective data. METHODS: School-based action
      research teams were recruited statewide by the New Hampshire Healthy Schools
      Coalition, the state team of the National Action for Healthy Kids Coalition.
      Action teams consisted of a physical education teacher, a school nurse, and a
      school administrator. Data were collected from 6,511 student participants aged 6
      to 14 years, which was a representative cross-section from New Hampshire school
      districts. Key variables of interest in the study were body mass index, and
      ability to pass five fitness tests using FITNESSGRAM. Pearson's correlation was
      used to assess the relationships among body mass index, age, gender, and the
      percent of students that passed FITNESSGRAM tests. RESULTS: The ability of
      participants to pass the FITNESSGRAM tests declined markedly with age and
      differed between boys and girls, although the healthy fitness zones for any
      particular test was lower for girls. Body mass index was significantly negatively
      correlated with performance on all tests. Age was also statistically negatively
      correlated with performance on all tests; the relationship between gender and
      performance on the tests was less striking. CLINICAL IMPLICATIONS: Results
      reflected an increase in the prevalence of overweight school children, even in
      New Hampshire, which is purported to be one of the healthiest states in the
      nation. Results offered evidence that body mass index is a valid proxy measure
      for fitness levels and that fitness programs are necessary to effectively combat
      the obesity epidemic. Evidence-based changes need to be implemented to address
      obesity-related factors in schools, because children spend many of their waking
      hours in that setting. Physical activity during recess and physical education
      classes could help to increase energy expenditure and develop sound minds and
      bodies. Schools should consider the development of school-based wellness teams to
      advise and advocate improved school-based wellness policies. School nurses can
      take an active part in these initiatives.

PMID- 18327110
TI  - Addressing the childhood obesity crisis: a call to action.
AB  - The prevalence of childhood obesity is increasing in the United States and
      globally. Associated with numerous comorbid conditions, childhood obesity is also
      recognized as a risk factor for multiple chronic conditions and premature
      mortality in adult life. Children and adolescents, particularly those from ethnic
      minorities and rural low income populations, bear an excess burden of obesity and
      its attendant comorbidities. A major contributor to childhood obesity is a
      physical and social environment that promotes foods high in fat and calories and
      minimizes the opportunities for physical activity. Despite the strong
      environmental influences that encourage overeating and sedentary behavior, weight
      maintenance is viewed as a personal responsibility. Addressing the obesity crisis
      requires a paradigm shift away from blaming individuals for the lack of will
      power to control their eating and physical activity to one of recognizing the
      "toxic" or "obesigenic" environment as a primary determinant. This article
      addresses the obesity crisis from individual, family, local community, and public
      policy perspectives. Emphasis is placed on the role of nurses and nursing, acting
      to promote change with individuals and families and acting as advocates for
      multilevel policy initiatives, in reversing the epidemic and improving the health
      of future generations.

PMID- 18327112
TI  - State of the Science on postpartum depression: what nurse researchers have
      contributed--part 1.
AB  - Postpartum depression has been described as a thief that steals motherhood. It
      can result in tragedy and sometimes in headline-gripping maternal suicide or
      infanticide. Because one of the highest priorities for nursing is to continually
      advance the knowledge that underlies nursing practice, it is essential that we
      understand what nurse researchers have done to advance the knowledge base of
      postpartum depression. This integrative review is a two-part series for MCN that
      summarizes 141 postpartum depression studies conducted by nurse researchers from
      around the globe, including United States, Australia, Canada, China (Hong Kong,
      Taiwan), Finland, Iceland, Sweden, Turkey, and Malaysia. Specific areas of
      postpartum depression to which nurse researchers have devoted their primary
      attention include epidemiology, risk factors, transcultural perspectives,
      instrument development, screening, interventions, and mother-infant interactions.

PMID- 18327113
TI  - Helping breastfeeding mothers eat well.

PMID- 18327114
TI  - Newborn identification and barcodes.

PMID- 18327115
TI  - Cesarean birth rates: global trends.

PMID- 18327117
TI  - Medication safety with heparin.

PMID- 18327118
TI  - New guidelines for diagnosis and management of asthma.

PMID- 18327119
TI  - Sex hormone receptors and testosterone in postmenopausal women.

PMID- 18327120
TI  - To the editor. Inability to make a correlation between levels of serum
      testosterone and scores derived from a 10-question screening tool known as the
      Androgen Deficiency in Aging Males questionnaire.

PMID- 18327124
TI  - Evidence-based recommendations: time, implementation, and strength of evidence.

PMID- 18327125
TI  - Hyperglycemia in the pediatric intensive care unit: a few steps closer to
      sweetening the pot.

PMID- 18327126
TI  - Improving our approach to sedation in the pediatric intensive care unit: is it
      time to inhale?

PMID- 18327127
TI  - Approaching parents for organ donation: who and when?

PMID- 18327128
TI  - Slowing down hypermetabolism: first follow the basic steps.

PMID- 18327129
TI  - Odds ratios, and odd musings, about neonatal septic shock.

PMID- 18327130
TI  - Review of retinal angiomatous proliferation or type 3 neovascularization.

PMID- 18327131
TI  - Fundus autofluorescence imaging: review and perspectives.
AB  - Fundus autofluorescence (FAF) imaging is a novel imaging method that allows
      topographic mapping of lipofuscin distribution in the retinal pigment epithelium
      cell monolayer as well as of other fluorophores that may occur with disease in
      the outer retina and the subneurosensory space. Excessive accumulation of
      lipofuscin granules in the lysosomal compartment of retinal pigment epithelium
      cells represents a common downstream pathogenetic pathway in various hereditary
      and complex retinal diseases, including age-related macular degeneration. FAF
      imaging has been shown to be useful with regard to understanding of
      pathophysiologic mechanisms, diagnostics, phenotype-genotype correlation,
      identification of predictive markers for disease progression, and monitoring of
      novel therapies. FAF imaging gives information above and beyond that obtained by
      conventional imaging methods, such as fundus photography, fluorescein
      angiography, and optical coherence tomography. Its clinical value coupled with
      its simple, efficient, and noninvasive nature is increasingly appreciated. This
      review summarizes basic principles and FAF findings in various retinal diseases.

PMID- 18327132
TI  - Pars plana vitrectomy with internal limiting membrane peeling for diabetic
      macular edema.
AB  - PURPOSE: To evaluate anatomic and visual acuity (VA) results of pars plana
      vitrectomy (PPV) with internal limiting membrane (ILM) peeling for diffuse
      diabetic macular edema (DME), and to review the literature on the topic. METHODS:
      Retrospective noncomparative case series of patients who underwent PPV with ILM
      peeling for diffuse DME between January 1, 2000, and December 1, 2005, performed
      by three surgeons at Bascom Palmer Eye Institute. Main outcome measures included
      pre- and postoperative optical coherence tomography (OCT) and visual acuity. Mean
      follow-up period was 8 months (range, 43 days-2 years). RESULTS: Twenty-four eyes
      of 23 patients meeting the criteria were evaluated. Duration of DME ranged from 1
      to 93 months. Mean preoperative logMAR vision was 0.782 (range, 0.30-1.82). Mean
      logMAR visual acuity at final follow-up was 0.771 (range, 0.10-2.00). At last
      follow-up, 25% of eyes had > or =2 line increase in VA from baseline, 54% of eyes
      had no improvement in VA, and 21% of eyes had > or =2 line decrease in VA. Of 9
      eyes with pre- and postoperative OCT, there was an overall reduction in central
      macular thickness of 141 microm at postoperative month 3 and 120 microm at last
      follow-up. Postoperative complications included progression of cataract in 6
      (60%) of 10 phakic eyes, postoperative intraocular pressure > or =30 mmHg in 6
      (24%) eyes, and postoperative vitreous hemorrhage in 2 (8%) eyes. CONCLUSIONS:
      Pars plana vitrectomy with ILM peeling was associated with a reduction in DME
      when measured by OCT in the majority of eyes, but visual acuity outcomes showed
      minimal improvement compared to baseline. These results suggest the efficacy of
      PPV with ILM peeling for eyes with DME has not been well established and should
      be reserved for therapy with selected cases.

PMID- 18327133
TI  - Surgical and anatomical outcomes of pars plana vitrectomy for diffuse
      nontractional diabetic macular edema.
AB  - PURPOSE: To prospectively determine the efficacy of vitrectomy combined with
      intravitreal triamcinolone acetonide (IVTA) injection, internal limiting membrane
      (ILM) peeling, or both in treating diffuse nontractional diabetic macular edema
      (ME). METHODS: Patients with diffuse ME of <6 months who had no evidence of
      macular traction or macular ischemia were included in the study. Patients
      previously diagnosed with glaucoma underwent vitrectomy with ILM peeling. All
      other patients were randomly assigned to vitrectomy or vitrectomy with ILM
      peeling followed by IVTA injection. RESULTS: Forty-two eyes of 38 patients were
      included in the study. Mean follow-up was 12 months. A statistically significant
      reduction in macular thickness was found at 1 month to 6 months, disappearing at
      12 months. No differences in visual acuity between treatment groups were found
      during follow-up. Visual acuity improved in 5 (12%) of 42 eyes, remained
      unchanged in 32 (76%) of 42 eyes, and worsened in 5 (12%) of 42 eyes.
      Complications included increase in intraocular pressure in 8 (26%) of 31 eyes,
      mild vitreous hemorrhage in 6 (14%) of 42 eyes, central retinal pigment
      epithelium changes in 5 (12%) of 42 eyes, and cataract progression in 11 (38%) of
      29 phakic eyes. CONCLUSION: In diffuse diabetic ME with no retinal traction,
      vitrectomy with either ILM peeling or IVTA injection at the end of surgery
      produces a short-term improvement in retinal thickness but no long-term
      anatomical or functional improvements.

PMID- 18327134
TI  - Macular hole surgery with triamcinolone acetonide-assisted internal limiting
      membrane peeling: one-year results.
AB  - PURPOSE: To report the 1-year results of macular hole surgery with triamcinolone
      acetonide (TA)-assisted internal limiting membrane (ILM) peeling and to compare
      those with results of indocyanine green (ICG)-assisted ILM peeling. METHODS: In a
      nonrandomized, retrospective, interventional case series, 40 eyes of 39
      consecutive patients with idiopathic full-thickness macular holes underwent
      macular hole surgery with TA-assisted ILM peeling. Surgical results 1 year after
      surgery, including changes in best-corrected visual acuity (BCVA) and macular
      hole closure, were evaluated. Moreover, we compared the results for these 40 eyes
      (TA group) with those for 27 eyes of 27 consecutive patients who had undergone
      macular hole surgery with 0.25% ICG-assisted ILM peeling (ICG group). RESULTS: In
      the TA group, macular holes were closed in 39 (98%) of 40 eyes. Mean BCVA +/- SD
      significantly improved from 0.78 +/- 0.31 logarithm of the minimal angle of
      resolution (logMAR) preoperatively to 0.20 +/- 0.30 logMAR (P < 0.001). BCVA
      improved by > or =0.2 logMAR in 37 eyes (93%). BCVA was 20/40 or better in 33
      (83%) of 30 eyes. In the ICG group, macular holes were closed in all 27 eyes
      (100%), and mean BCVA +/- SD significantly improved from 0.81 +/- 0.4 logMAR
      preoperatively to 0.34 +/- 0.2 logMAR 1 year postoperatively (P < 0.001). BCVA
      improved by > or =0.2 logMAR in 22 eyes (81%). BCVA was 20/40 or better in 16
      (59%) of 27 eyes. Significant differences between groups were seen in mean BCVA 1
      year after surgery (P = 0.049) but not in BCVA of 20/40 or better (P = 0.17) or
      change in BCVA by > or =0.2 logMAR (P = 0.05). CONCLUSION: TA is useful as an
      adjuvant for ILM peeling in macular hole surgery, and BCVA 1 year after surgery
      might be more favorable when compared with ICG-assisted ILM peeling.

PMID- 18327135
TI  - Tearing and folding of the retinal internal limiting membrane associated with
      macular epiretinal membrane.
AB  - PURPOSE: To describe the clinical and histologic features of a particular form of
      macular epiretinal membrane. METHODS: The charts of all patients operated for
      macular epiretinal membrane by a single surgeon (E.H.B.) between June 2001 and
      January 2005 were retrospectively reviewed. Patients with macular epiretinal
      membrane associated with tearing and folding of the internal limiting membrane
      (ILM) were identified and the following parameters were recorded when available:
      age, gender, best-corrected visual acuity before and after vitrectomy; optical
      coherence tomography; pre-, intra-, and postoperative macular status;
      intraoperative staining by indocyanine green; histology. RESULTS: Twenty-three of
      268 eyes (8.6%) with macular epiretinal membrane were associated with tearing and
      folding of the ILM, forming a whitish prominent band on the surface of the
      retina. The mean age of the patients was 68.6 years with a significant female
      predominance (78.3%). The vitreous was completely detached in 21 eyes. After
      surgical peeling, the mean visual gain was 3.2 Early Treatment Diabetic
      Retinopathy Study lines. No recurrence was observed. CONCLUSION: Tearing and
      folding of the ILM was associated with macular epiretinal membranes in 8.6% of
      cases. The ILM was probably torn during posterior hyaloid detachment, but the
      pathogenesis has not been clearly elucidated. The surgeon should begin to peel
      the macular epiretinal membrane by grasping the folded ILM to ensure complete
      removal of the ILM together with the epiretinal membrane. The postoperative
      visual prognosis was good.

PMID- 18327136
TI  - Optical coherence tomography of optic disk melanocytoma in 15 cases.
AB  - OBJECTIVE: To describe the optical coherence tomography (OCT) features of optic
      disk melanocytoma. DESIGN AND PARTICIPANTS: Case series including 15 patients.
      MAIN OUTCOME MEASURES: OCT characteristics of the tumor. RESULTS: The mean age of
      the patients was 42 years. By ophthalmoscopy, the mean basal diameter of the
      tumor was 2.7 mm, and by ultrasonography, the mean thickness was 1.8 mm. By OCT,
      the tumor showed a nodular appearance in 14 cases (93%). The tumor displayed a
      gradual sloping transition from normal retina into the mass, hyperreflectivity at
      its anterior tumor surface, and dense posterior shadowing with an optically empty
      appearance in all 15 cases (100%). Thicker tumors displayed thinner anterior
      hyperreflective borders and denser shadowing. There were no internal qualities of
      the tumor or disk visible by OCT due to dense shadowing. Other findings of OCT
      included vitreous seeds in 2 cases (13%) and adjacent retinal edema in 1 case
      (7%). There were no cases of retinal traction, subretinal fluid, macular edema,
      or epiretinal membrane in the macula. CONCLUSIONS: Optic disk melanocytoma shows
      characteristic features by OCT including a gradual transition from normal retina
      into nodular tumor, and the mass displays a bright anterior border layer with
      optically empty internal details.

PMID- 18327137
TI  - Multifocal retinal contraction in macular pucker analyzed by combined optical
      coherence tomography/scanning laser ophthalmoscopy.
AB  - PURPOSE: To characterize the topography of macular pucker using coronal plane
      imaging in vivo, and correlate this with transverse optical coherence tomography
      (OCT) to assess the relationship between topographic features and severity of
      disease. METHODS: Forty-four eyes with macular pucker underwent full
      ophthalmologic evaluation including B-scan ultrasonography as well as coronal and
      transverse plane imaging with combined OCT/scanning laser ophthalmoscopy (SLO).
      RESULTS: Posterior vitreous detachment was present in 37/44 eyes (84.1%) by
      ultrasound. Multiple foci of retinal contraction were detected in 20/44 eyes
      (45.5%) by coronal plane OCT/SLO. Intraretinal cysts were present in 6/9 (66.7%)
      eyes with three or four contraction centers as compared to 10/35 (28.6%) eyes
      with one or two contraction centers (P = 0.05). Eyes with three or four
      contraction centers had significantly (P = 0.05) thicker maculae (369 +/- 98
      microm) compared to those with one or two contraction centers (297 +/- 110
      microm). CONCLUSION: Coronal plane imaging detected multifocality in nearly half
      of eyes with macular pucker. Eyes with multiple retinal contraction centers had
      greater retinal damage compared to eyes with one or two contraction centers.
      Multifocal retinal contraction may have clinical significance in that it may
      impact on prognosis and management.

PMID- 18327138
TI  - Correlation of visual recovery and presence of photoreceptor inner/outer segment
      junction in optical coherence images after successful macular hole repair.
AB  - PURPOSE: To determine the relationship between the postoperative visual acuity
      (VA) and the presence of a photoreceptor inner segment (IS) and outer segment
      (OS) junction (IS/OS) in optical coherence tomographic (OCT) images after macular
      hole (MH) surgery. METHODS: Twenty-three eyes of 23 cases of idiopathic MH
      treated by vitrectomy were studied. The postoperative VA and OCT3 images of the
      fovea at 1, 3, and 6 months were examined. The relationship between the presence
      of the IS/OS junction and the visual acuity was studied. RESULTS: All MHs were
      successfully closed. The IS/OS junction appeared as a distinct, highly reflective
      line just vitread to the retinal pigment epithelial layer in the postoperative
      OCT3 images. A normal IS/OS junction was detected postoperatively in one eye at 1
      month, three eyes at 3 months, and seven eyes at 6 months. The VA was
      significantly better in eyes in which a normal IS/OS junction was detected than
      in those not detected at 3 and 6 months postoperatively (P = 0.046 and P = 0.040,
      respectively). CONCLUSION: The normal IS/OS junction observed in OCT3 images is
      associated with good visual recovery after MH closure. The presence of normal
      IS/OS junction may be important for visual recovery after MH repair.

PMID- 18327139
TI  - Cross-sectional and en face optical coherence tomographic features of polypoidal
      choroidal vasculopathy.
AB  - PURPOSE: To correlate optical coherence tomography (OCT)-ophthalmoscope images
      with angiographic signs of polypoidal lesions and branching network vessels in
      eyes with polypoidal choroidal vasculopathy (PCV). METHODS: The authors
      prospectively examined 50 consecutive eyes with PCV using the OCT-ophthalmoscope
      and fluorescein and indocyanine green angiography (ICGA). RESULTS: ICGA showed
      polypoidal lesions in all eyes. In 18 of 22 eyes with a retinal pigment
      epithelial detachment (PED), OCT-ophthalmoscope cross-sectional B-scan images
      showed a central dome-shaped PED and a contiguous small PED corresponding to the
      polypoidal lesions on ICGA. Transverse C-scan images showed an irregularity or
      protrusion of the highly reflective retinal pigment epithelium (RPE) line of the
      PED corresponding to the polypoidal lesions on ICGA in all 22 eyes. In 28 eyes
      without a PED, the B-scan images showed polypoidal lesions as anterior
      protrusions of a highly reflective RPE line in 26 of 28 eyes; in those 26 eyes, C
      scan images showed distinctive rings of a highly reflective RPE line
      corresponding to the polypoidal lesions on ICGA. ICGA showed an abnormal vascular
      network in 41 of the 50 eyes that appeared as a highly reflective area on C-scan
      images in 32 of the 41 eyes. In 20 of the 41 eyes, B-scan images showed two
      separate highly reflective RPE lines at the area of the abnormal vascular
      network. CONCLUSIONS: The OCT-ophthalmoscope C-scan images of the irregularity
      and the protrusion in the PED and the distinctive bright rings in eyes without a
      PED may be diagnostically important as indicators of polypoidal lesions in eyes
      with PCV.

PMID- 18327140
TI  - Efficacy of intravitreal triamcinolone for the treatment of macular edema
      secondary to branch retinal vein occlusion in eyes with or without grid laser
      photocoagulation.
AB  - PURPOSE: To evaluate the efficacy of primary and secondary (following grid laser
      photocoagulation) intravitreal triamcinolone acetonide (IVTA) injection for the
      treatment of macular edema associated with branch retinal vein occlusion (BRVO).
      METHODS: Eyes with macular edema secondary to BRVO and best-corrected visual
      acuity (BCVA) worse than 20/40 were included. Eyes eligible for Branch Retinal
      Vein Occlusion Study (BVOS) guidelines received grid laser treatment first. Those
      that were not improved at least two lines following grid laser or that did not
      meet those guidelines received 4 mg IVTA injection. The efficacy of IVTA
      treatment was assessed by analyzing the change in BCVA and reduction in central
      macular thickness (CMT) measured by optical coherence tomography. Intraocular
      pressure (IOP) spikes and other complications were recorded. RESULTS: The data
      from 37 eyes were included; in 12 of them IVTA injection was given after grid
      laser while 25 of them received IVTA as a primary treatment. Mean follow-up was
      9.6 +/- 4.5 months. BCVA was 0.06 +/- 0.30 and 0.17 +/- 0.50 in the primary and
      secondary IVTA injection groups, respectively. In the primary injection group,
      there was a statistically significant gain in BCVA throughout the follow-up (P <
      0.05), while a small increase in BCVA was noted only at the third month visit in
      the secondary IVTA injection group (P = 0.04). Average CMT were 434.8 +/-
      122.1microm and 389.0 +/- 171.9 microm before IVTA injection in the two groups,
      respectively. In the primary IVTA injection group, CMT decreased at 1 month
      following IVTA injection and remained statistically significant until the sixth
      month visit (P < 0.05). In the secondary IVTA injection group, a slight reduction
      in CMT was noted only in the first month visit (P = 0.02). Pre-IVTA BCVA was
      found to be the single statistically significant predictor of BCVA gain following
      IVTA injection. In 8 patients (21.6%), the IOP increased above 25 mmHg
      postoperatively, and was successfully managed by medical treatment.
      Endophthalmitis did not develop in any of the patients. CONCLUSION: IVTA
      injection produced a significant reduction of macular edema in eyes with BRVO
      either with or without prior grid laser treatment. Reduction of CMT increased the
      BCVA in most of the eyes receiving IVTA primarily, while only a slight
      improvement of BCVA was found in eyes with prior grid laser. The IVTA effect was
      transient. Larger studies are necessary to find the best approach (either grid
      laser or IVTA) to patients with macular edema associated with BRVO.

PMID- 18327141
TI  - Vitreal penetration of oral moxifloxacin in humans.
AB  - PURPOSE: To investigate the vitreal penetration of moxifloxacin after oral
      administration. DESIGN: Prospective, nonrandomized clinical series. METHODS:
      Twenty-four patients (mean age = 62.8 years) undergoing elective pars plana
      vitrectomy were assigned to a dosing group: control (n = 3), which received no
      medication; single-dose (n = 11), which received one 400 mg oral dose of
      moxifloxacin 3 hours before surgery; and five-dose (n = 10), which received one
      400 mg dose on each of the 4 days preceding surgery and a fifth dose 3 hours
      before surgery. Vitreous samples were obtained and analyzed. RESULTS: Control,
      below quantifiable levels; single-dose, 0.572 +/- 0.239 microg/mL; and five-dose,
      1.200 +/- 0.645 microg/mL. CONCLUSIONS: Five doses of oral moxifloxacin lead to
      higher intravitreal drug concentrations than single-dose administration. Both
      regimens, however, achieve levels that exceed the MIC90 of many bacteria
      implicated in postoperative endophthalmitis.

PMID- 18327142
TI  - Induction of retinochoroidal venous anastomosis in central retinal vein occlusion
      with macular edema via a full-thickness retinochoroidal incision.
AB  - PURPOSE: To report the induction of retinochoroidal venous anastomosis (RCVA) in
      the treatment of nonischemic central retinal vein occlusion (CRVO) with macular
      edema via a full-thickness retinochoroidal incision. METHODS: In nine eyes with
      nonischemic CRVO and intractable macular edema, one or two full-thickness
      incisions transacting a major retinal branch vein to the level of inner sclera
      were made in conjunction with vitrectomy. Fluorescein angiography was conducted
      to evaluate the formation of functional RCVA. Best-corrected visual acuity (BCVA)
      and central macular thickness (CMT) were compared before and after the surgery.
      RESULTS: The mean follow-up period +/- SD was 12.0 +/- 5.1 months. All nine eyes
      developed functional RCVA after the surgery. The mean BCVA +/- SD improved from
      0.75 +/- 0.30 logMAR (logarithm of the minimal angle of resolution) to 0.55 +/-
      0.26 logMAR (P = 0.018), and the mean CMT +/- SD was reduced from 686 +/- 265
      microm to 251 +/- 150 microm (P = 0.011). Additional surgery was performed on one
      eye due to persistent vitreous hemorrhage. CONCLUSION: Full-thickness
      retinochoroidal incision appears to raise the rate of successful RCVA formation
      and may improve the outcome of CRVO with macular edema.

PMID- 18327143
TI  - Low redetachment rate due to encircling scleral buckle in giant retinal tears
      treated with vitrectomy and silicone oil.
AB  - BACKGROUND: The goal of this study was to identify risk factors for redetachment
      and to assess long-term anatomic and functional results of pars plana vitrectomy
      (PPV) for retinal detachment associated with giant retinal tears (GRT). SUBJECTS
      AND METHODS: In a retrospective study the authors analyzed 30 eyes which were
      operated with PPV for GRT retinal detachment in their clinic between March 1998
      and August 2003. RESULTS: Redetachment rate after one vitrectomy procedure in
      this series of 30 eyes was 30% (n = 9), and ultimately, the retina was attached
      in 29 (96.7%) eyes. After multivariate analysis the absence of an encircling
      scleral buckle (P = 0.008) was significantly associated with redetachment. Visual
      acuity improved in 54% of the eyes. CONCLUSION: Vitrectomy with an encircling
      scleral buckle seems to be a preferred treatment for complicated retinal
      detachments due to GRT.

PMID- 18327144
TI  - Reduced choroidal blood flow can induce visual field defect in open angle
      glaucoma patients without intraocular pressure elevation following encircling
      scleral buckling.
AB  - PURPOSE: To determine the cause of the progressive glaucomatous visual field
      defects in three patients after an encircling scleral buckle for a rhegmatogenous
      retinal detachment (RRD). METHODS: Scanning laser Doppler flowmetry and visual
      field tests were performed on three cases with unilateral progressive visual
      field defect after an encircling scleral buckling for a RRD. Similar measurements
      were made after the buckle was removed. RESULTS: After implanting the scleral
      buckle, the intraocular pressure was normal and chamber angle was open. The blood
      flow in the neuroretinal rim of the optic disk was lower than that in the healthy
      fellow eye. After removing the buckle, the blood flow improved to normal levels
      and a further worsening of the visual field was not detected. CONCLUSIONS: These
      results suggest that an encircling scleral buckle may impair choroidal
      circulation and lead to visual field defects similar to eyes with normal tension
      glaucoma.

PMID- 18327145
TI  - Angiographic evidence for revascularization of an rpe-choroid graft in patients
      with age-related macular degeneration.
AB  - PURPOSE: To study graft perfusion using fluorescein angiography (FA) and
      indocyanine green angiography (ICG) after the translocation of an autologous
      retinal pigment epithelium (RPE)-choroid graft in patients with exudative age
      related macular degeneration (AMD). METHODS: Retrospective observational case
      series of 31 patients with AMD who had FA and/or ICG performed after an RPE
      choroid graft translocation. The FAs (n = 25) and ICGs (n = 23) were assessed by
      an independent masked reader for the presence of early fluorescence of the graft
      in FA, and for perfusion of the choroidal vessels of the graft and recipient bed
      in ICG. RESULTS: Early fluorescence of the graft was present in 23 of the 25 FAs.
      Perfusion of the graft vasculature was observed in 12 of the 23 ICGs. The two
      grafts that lacked early fluorescence in FA also had no signs of choroidal
      perfusion of the graft and the recipient bed with ICG. CONCLUSION:
      Revascularization of the RPE-choroid graft was observed in all but 2 of the 31
      patients either by early fluorescence of the graft by FA or by identification of
      perfused choroidal graft vessels with ICG from 1 week up to 3 years after
      surgery. For assessment of revascularization of the graft evaluation of the early
      phase of the FA is recommended.

PMID- 18327146
TI  - A moephologic study of retinal toxicity induced by triamcinolone acetonide
      vehicles in rabbit eyes.
AB  - PURPOSE: To evaluate the toxic effects of two triamcinolone acetonide (TA)
      vehicles on rabbit retina at different volumes. METHODS: Vehicle A and B were
      prepared from two TA injections by centrifugation. Thirty-six New Zealand white
      rabbits were intravitreally injected with vehicle A, B, or balanced saline
      solution at 0.1 mL or 0.2 mL respectively. The eyes were examined by indirect
      ophthalmoscope, light microscope, and transmission electron microscope up to week
      8 postinjection. RESULTS: Eyes with vehicle A appeared normal under the
      ophthalmoscope, but showed disorganization in retinal inner nuclear layer and
      photoreceptor layer in pathologic analyses. Eyes with vehicle B displayed more
      significant retinal changes including retinal hemorrhage, vascular narrowing,
      myelinated fiber edema, retinal necrosis and atrophy, and photoreceptor
      apoptosis. There was an increase in degree of the above damages as the volume of
      either vehicle increased. CONCLUSION: Both vehicle A and B caused volume-related
      toxicity in rabbit retina. The intensity of the toxic effects of different
      vehicles may differ. Reducing or decanting the vehicles should be considered
      before intravitreal use of TA injections.

PMID- 18327147
TI  - Morphine pretreatment provides histologic protection against ischemia-reperfusion
      injury in rabbit retina.
AB  - PURPOSE: Pharmacologic preconditioning with morphine has been shown to protect
      several kinds of tissues against ischemia-reperfusion injury. The aim of the
      present study was to investigate whether intravitreal administration of morphine
      induces structural protection against ischemic damage in a rabbit model of
      ischemic retinopathy. METHODS: Twenty-eight male white New Zealand rabbits were
      used. Animals in saline control group received 0.1 mL of phosphate-buffered
      saline (PBS) intravitreally with no postinjection ischemia. In the saline-control
      ischemia group, 15 minutes after injection of PBS, retinal ischemia was induced
      by raising intraocular pressure to 150 mmHg for 60 minutes. In three treatment
      ischemia groups, morphine (1, 5, and 10 micromol/L) was administered
      intravitreally 15 minutes before induction of ischemia. In another experiment,
      naloxone (40 micromol/L) was administered 5 minutes before intravitreal
      administration of morphine (10 micromol/L) followed by 60 minutes of ischemia to
      investigate the role of opioid receptors in mediating the possible protective
      effect of morphine. Toxicity controls were performed with morphine (10
      micromol/L) and naloxone (40 micromol/L) without ischemia. Histologic evaluation
      was performed for all groups on the seventh postoperative day. RESULTS: Sixty
      minutes of ischemia led to severe cell loss in ganglion cell layer and thinning
      of the inner nuclear layer in saline-control ischemia compared to that of the
      nonischemia control group (P < 0.001). Thickness of the inner plexiform layer to
      the inner limiting membrane was significantly increased due to edema (P < 0.001).
      Administration of morphine in higher doses (5 and 10 micromol/L) significantly
      improved all of the above mentioned indices (P < 0.05). Administration of
      naloxone 15 minutes before morphine reversed most of the morphine protective
      effects. CONCLUSIONS: Morphine pretreatment provides significant histologic
      protection against ischemic injury in rabbit retina. Pharmacologic evidence
      suggests that this protective phenomenon may be mediated in part by opiate
      receptors.

PMID- 18327148
TI  - 27-gauge Twinlight chandelier illumination system for bimanual transconjunctival
      vitrectomy.

PMID- 18327149
TI  - Diagnostic and therapeutic challenges.

PMID- 18327150
TI  - Celiac disease presenting as a xerophthalmic fundus.

PMID- 18327151
TI  - Correspondence.

PMID- 18327152
TI  - Bone turnover marker profile in relation to the menstrual cycle of premenopausal
      healthy women.
AB  - OBJECTIVE: To explore the bone turnover marker profile during the menstrual cycle
      of premenopausal women. DESIGN: This was a noninterventional study. Levels of
      bone turnover markers, including serum C-terminal telopeptide of type I collagen
      (sCTX), bone-specific alkaline phosphatase, osteocalcin, procollagen type 1 N
      propeptide, and urinary N-terminal telopeptide of type I collagen, were measured
      in blood and urine samples during one menstrual cycle. Levels were expressed as
      raw test results and percent change from serum luteinizing hormone peak.
      Differences in mean levels of bone turnover markers between menstrual phases and
      subphases were examined. RESULTS: Fifty-five women comprised the per-protocol
      population. Mean sCTX values were 0.48 ng/mL during the follicular phase (FP),
      0.47 ng/mL at serum luteinizing hormone peak, and 0.43 ng/mL during the luteal
      phase (LP). Additionally, the mean percent change from luteinizing hormone peak
      varied from +4.35% during the FP to -5.11% during the LP (P = 0.0014). Mean sCTX
      levels during the early and through mid FP were significantly higher than levels
      during the mid and late LP. The pattern for urinary N-terminal telopeptide of
      type I collagen was similar to that of sCTX but not statistically significant.
      There was a statistically significant tendency for procollagen type I N
      propeptide levels to be lower during the FP relative to the LP. Levels of
      osteocalcin and bone-specific alkaline phosphatase did not vary significantly
      during the menstrual cycle. CONCLUSIONS: Levels of some bone turnover markers
      varied during the menstrual cycle. A statistically significant change in sCTX
      (9.46%) occurred between the FP and LP of the menstrual cycle.

PMID- 18327153
TI  - Fructus ligustri lucidi extract improves calcium balance and modulates the
      calciotropic hormone level and vitamin D-dependent gene expression in aged
      ovariectomized rats.
AB  - OBJECTIVE: Fructus ligustri lucidi (FLL) is a widely used herb in China that is
      classically included in antiaging formulas for the treatment of age-related
      symptoms. Our laboratory previously showed that FLL could regulate calcium
      balance in young ovariectomized (OVX) rats. In the present study, we aimed to
      determine whether FLL could regulate calcium balance in aged OVX rats and to
      study the potential mechanisms that mediate its action in vivo. DESIGN: Aged OVX
      rats were orally administered an ethanol extract of FLL and its vehicle and fed
      with diets containing different levels of calcium [low calcium diet (LCD), 0.1%
      Ca; medium calcium diet (MCD), 0.6% Ca; and high calcium diet (HCD), 1.2% Ca] for
      12 weeks. RESULTS: Significant reductions in urinary and fecal calcium excretion
      were found in the FLL-treated animals, resulting in a significant induction of
      calcium retention in rats fed with the MCD and HCD. FLL treatment significantly
      increased the serum 1,25-dihydroxyvitamin D3 level and slightly decreased the
      serum parathyroid hormone level in OVX rats fed with the MCD and HCD. When OVX
      rats were challenged by LCD, the inductions of serum parathyroid hormone and 1,25
      dihydroxyvitamin D3 were decreased by FLL administration. FLL treatment
      significantly up-regulated duodenal vitamin D receptor and calcium transport
      protein 1 mRNA expression in rats fed with the HCD. FLL treatment reduced the
      expression of renal vitamin D receptor and 25-hydroxyvitamin D-24-hydroxylase
      mRNA in OVX rats fed with the LCD and MCD. CONCLUSIONS: Twelve weeks of FLL
      treatment could reduce calcium loss, modulate the parathyroid hormone-vitamin D
      axis, and increase vitamin D-dependent calcium transport in aged OVX rats,
      suggesting that FLL might be useful as an alternative medicine for improving
      calcium balance in postmenopausal women.

PMID- 18327155
TI  - Laser bladder perforation from photoselective vaporization of prostate resulting
      in rhabdomyolysis induced acute renal failure.
AB  - Hyponatremia and its related comorbidities remain a concern after traditional
      transurethral resection of the prostrate (TURP). Photoselective vaporization of
      the prostate (PVP) laser coagulation therapy is a new, relatively bloodless
      procedure for treatment of benign prostatic hyperplasia (BPH). Perceived benefits
      with PVP laser TURP include excellent visualization of the operative field during
      urethral prostatic tissue vaporization and the reduced incidence of laser
      penetration through the prostatic capsular fibers once the capsule is reached.
      Theoretically, this would provide a low risk method of perforation during laser
      TURP. After literature review, we report this as the first case of laser bladder
      perforation as a complication arising from PVP therapy. This case report
      discusses the management of acute hyponatremic induced rhabdomyolysis with acute
      renal failure (ARF) and the recommendation to use sodium chloride vs. sterile
      water for bladder irrigation during PVP TURP procedures.

PMID- 18327154
TI  - Expression of hepatocyte transporters and nuclear receptors in children with
      early and late-stage biliary atresia.
AB  - To investigate how the liver adapts to chronic obstructive cholestasis, liver
      samples from infants with early- and late-stage cholestasis were analyzed for
      changes in the levels of hepatocyte transporters and nuclear receptors. At early
      stage cholestasis, most canalicular transporters and sinusoidal uptake
      transporters were downregulated, including bile salt export pump (BSEP, ABCB11),
      multidrug resistant protein 3 (MDR3, ABCB4), multidrug-resistant associated
      protein 2 (MRP2, ABCC2), sodium-dependent taurocholate cotransporting polypeptide
      (NTCP, SLC10A1), organic anion transporter (OATP, SLCO1A2), and nuclear receptor
      farnesoid X receptor (FXR, NR1H4). At late-stage cholestasis, FXR-BSEP levels
      returned to normal, MDR3 and MDR1 (ABCB1) were upregulated, and MRP-2 was
      downregulated. In addition, alternative sinusoidal efflux transporters, organic
      solute transporter alpha/beta (OSTalpha/beta) and MRP4 were upregulated, and
      pregnane X receptor (PXR, NR1I2) levels decreased. Cytochrome enzyme P450 7A1 was
      markedly downregulated at both early and late-stage cholestasis. An analysis of
      the long-term prognosis of 18 patients revealed lower PXR and constitutive
      androstane receptor (CAR, NR1I3) levels in the poor prognosis group. In
      conclusion, at long-term cholestasis, hepatocyte bile efflux was through
      sinusoidal and canalicular transporters, with FXR-BSEP levels maintained and PXR
      downregulated. Low PXR and CAR levels were associated with poor prognosis.

PMID- 18327156
TI  - Hypotony and choroidal detachment as a complication of travoprost after
      trabeculectomy surgery.

PMID- 18327157
TI  - Surgically induced astigmatism in phacoemulsification, pars plana vitrectomy, and
      combined phacoemulsification and vitrectomy: a comparative study.
AB  - PURPOSE: To study the surgically induced astigmatism (SIA) in combined
      phacoemulsification and vitrectomy, and compare with that when either procedure
      is performed alone. METHODS: This is a prospective comparative interventional
      trial comprising of 60 eyes of 60 consecutive patients with cataract and/or
      vitreo-retinal pathology. They were divided equally into three groups based on
      the type of procedure: Group A, phacoemulsification alone group, using a 3.0-3.2
      mm wide unsutured sclero-corneal tunnel incision at 1.0 mm post-limbus at 10
      o'clock; Group B, par plana vitrectomy alone group, using three sclerotomies at
      3.5 mm post-limbus at 2, 8, and 10 o'clock (right eye) or at 2, 4, and 10 o'clock
      (left eye) positions; and Group C, combined phacoemulsification and pars plana
      vitrectomy group. Main outcome measures were the amplitude (K-induced) and the
      axis of SIA calculated by rectangular coordinate method using the Holladay-Cravy
      Koch formula. RESULTS: The mean K-induced amplitudes were 0.19+/-0.14 D, 0.17+/
      0.11 D, and 0.23+/-0.19 D for groups A, B, and C, respectively. The range of K
      induced amplitudes for the entire cohort was 0.00-0.77 D. No overall
      statistically significant differences in the pre- and postoperative topographic
      astigmatism amplitudes and the K-induced between groups A, B, and C were found
      (all P>0.05). Minor shifts, of doubtful clinical significance, in the axes of SIA
      were present. CONCLUSIONS: Combined phacoemulsification and pars plana vitrectomy
      does not induce significant astigmatic change per se, and its amount is similar
      to that when either procedure is performed alone.

PMID- 18327158
TI  - The rabbit as an animal model for post-natal vitreous matrix differentiation and
      degeneration.
AB  - PURPOSE: This study evaluates whether rabbits are a suitable animal model to
      study post-natal vitreous differentiation and degeneration. METHODS: Human and
      rabbit eyes of various ages were studied by complementary anatomical techniques,
      light microscopy, and transmission electron microscopy. RESULTS: The global
      vitreous matrix organization is similar in human and rabbit eyes, lamellae are an
      important aspect thereof and show striking morphological changes with increasing
      age. In humans, liquefaction is more conspicuous than in rabbits but changes in
      matrix histology consistent with liquefaction can also be observed in the latter.
      CONCLUSIONS: Lamellar development is consistent with vitreous differentiation,
      while increasing liquefaction is consistent with matrix degeneration. At the
      anatomical and histological levels, human and rabbit vitreous matrices are
      sufficiently similar to make the rabbit a promising animal model for the study of
      the pathogenesis of vitreous matrix differentiation and degeneration in more
      detail.

PMID- 18327159
TI  - Open globe injuries in children: factors predictive of a poor final visual
      acuity.
AB  - AIMS: Eye injuries are the leading cause of monocular blindness in children and
      are challenging to manage. However, limited follow-up studies currently exist. We
      describe the clinical characteristics and outcomes of open globe injuries
      presenting to a major UK centre and discuss factors affecting long-term
      prognosis. PURPOSE: Identification of (1) demographic features, (2) causes, types
      and location of injuries, (3) initial clinical features and correlation with
      visual outcome, and (4) predictors of poor visual outcome. METHOD: Retrospective
      study by reviewing and analysing records of 20 patients, aged 16 years and below,
      who had undergone repair of an open globe injuries at the Manchester Royal Eye
      Hospital, UK. Data recorded included demographic data, mechanisms and location of
      injury, visual acuity, clinical signs on presentation, surgical procedures,
      postoperative complications, and final visual acuity. RESULTS: The study group
      comprised of 85% male subjects, 15% female subjects. The average age was 9.8
      years (range: 1-15). Average follow-up was 16.3 months (range: 3-48 months).
      Sharp objects (mainly glass or knife) accounted for the majority (65%) of
      injuries. Initial clinical signs associated with poor visual outcomes included
      poor initial visual acuity, cataract, RAPD, and no initial red reflex. Younger
      patients and blunt injuries (especially BB gun injuries) had worse visual
      outcomes. CONCLUSION: Factors suggesting unfavourable final visual acuity after
      open globe injuries in children are (1) young age at presentation, (2) poor
      initial visual acuity, (3) presence of a relative afferent papillary defect, (4)
      absence of red reflex, (5) cataract, and (6) types and number of surgeries
      performed.Awareness and education with regard to prevention of paediatric
      injuries need to be actively implemented.

PMID- 18327160
TI  - Aetiology and outcomes of adult superior oblique palsies: a modern series.
AB  - PURPOSE: To establish the contemporary aetiology of adult superior oblique palsy
      (SOP). MATERIALS AND METHODS: A retrospective consecutive case series of 150
      persons diagnosed with SOP between 1 January 1999 and 31 May 2005 at a neuro
      ophthalmology centre in the West Midlands, the United Kingdom. Interrogating two
      different hospital databases identified all cases. A case note review was
      performed on all participants to determine demographics and aetiology based on
      diagnostic criteria, neuroimaging used, and outcome. RESULTS: We identified 133
      unilateral isolated, 7 unilateral associated with other cranial nerve
      involvement, and 10 bilateral cases of SOP. Eighty-six were acquired, 51
      congenital, and 13 undetermined. Of the unilateral isolated cases, 38.3% were
      considered to be congenital, 29.3% followed trauma, 23.3% were presumed to be
      vasculopathic in origin, and no cause could be established in 7.5%. All presumed
      microvascular-associated palsies resolved within 6 months of presentation.
      Unilateral SOPs associated with other cranial nerve palsies were commonly caused
      by trauma (71.4%), followed by tumour and undetermined causes (both 14.3%).
      Trauma was the most frequent cause of bilateral SOP (50%), followed by tumours
      and undetermined causes (both 20%), with congenital causes being uncommon (10%).
      CONCLUSION: We present a contemporary aetiological spectrum for adult SOP, with
      the lowest incidence of undetermined cases published in the medical literature.
      Neuroimaging did not change the management for the vast majority of cases and
      should be prompted by atypical presentations.

PMID- 18327161
TI  - Macular holes: vitreoretinal relationships and surgical approaches.
AB  - Idiopathic full-thickness macular holes develop as a result of anteroposterior
      and tangential traction exerted by the posterior vitreous cortex at the fovea.
      Vitreoretinal relationships during the development of macular holes can be
      demonstrated in detail by ocular coherence tomography, facilitating an improved
      understanding of their pathogenesis and guiding clinical management. Surgical
      strategies for the repair of macular holes are designed to relieve vitreofoveal
      traction and to promote flattening and reapposition of the macular hole edges by
      intraocular gas tamponade. A period of face-down positioning postoperatively is
      conventionally advised. However, the evidence to support this recommendation is
      weak and practice varies considerably. Surgical removal of the inner limiting
      membrane (ILM) is advocated to ensure thorough removal of any tangential
      tractional components including any residual cortical vitreous. Current evidence
      suggests that ILM peeling can improve anatomical outcomes but the effect on
      visual function is less predictable; unsuccessful attempts to peel the ILM can be
      associated with poor visual outcome. The use of vital dyes can facilitate
      visualisation of the ILM and help achieve complete, atraumatic peeling.
      Indocyanine green dye can enable high rates of macular hole closure but has been
      associated with poorer visual outcomes suggesting a dose-dependent toxicity.
      Trypan blue dye offers an alternative that may have a more favourable risk
      profile. An improved understanding of vitreoretinal relationships may facilitate
      a tailored approach to surgery in individuals with macular holes. Vitrectomy to
      relieve anteroposterior traction is central in the management of all full
      thickness holes. The use of long-acting gases, prolonged face-down positioning,
      and ILM peeling may be more valuable for larger holes, longstanding holes, and
      those that have failed to close following conventional surgery.

PMID- 18327162
TI  - Pleomorphic adenoma of the lacrimal gland: is there a role for biopsy?
AB  - AIM: To review the literature on biopsy of lacrimal gland pleomorphic adenoma
      (LGPA) and to examine the validity of the prohibition against biopsy in LGPA.
      METHOD: Literature review. RESULTS: LGPA is usually diagnosed preoperatively
      based on clinical and radiological characteristics, as current teaching advises
      complete excision without prior incisional biopsy. The caveat against biopsy is
      based on older studies that reported increased recurrence rates with increased
      risk of malignant transformation after incomplete excision or biopsy. On the
      basis of a detailed examination of the literature on biopsy of both LGPA and
      pleomorphic adenoma of the salivary glands, it appears that there is no clear
      evidence to support the claim that biopsy increases the risk of recurrence or of
      malignant transformation of LGPA. CONCLUSION: Lacrimal gland tumours are uncommon
      lesions and optimal management depends to a great extent on a definite
      preoperative diagnosis. Preoperative biopsy should therefore be considered in all
      lacrimal gland mass lesions and management should be tailored to the biopsy
      findings. If surgical resection is then required, it may be prudent to excise the
      biopsy tract to ensure complete removal of the tumour.

PMID- 18327163
TI  - The use of intracameral phenylephrine in the management of intraoperative floppy
      iris syndrome with doxazosin.

PMID- 18327164
TI  - The Cataract National Dataset electronic multicentre audit of 55,567 operations:
      risk stratification for posterior capsule rupture and vitreous loss.
AB  - AIMS: To identify and quantify risk factors for posterior capsule rupture or
      vitreous loss or both (PCR or VL or both) during cataract surgery and provide a
      method of composite risk assessment for individual operations. METHODS: The
      Cataract National Dataset was extracted on 55,567 operations from 12 National
      Health Service (NHS) Trusts using an electronic patient record (EPR) system
      between November 2001 and July 2006. Risk indicators for variations in the rate
      of 'PCR or VL or both' were identified by univariate and multivariate analyses.
      Adjusted odds ratios (ORs) were used to formulate a composite 'bespoke' risk for
      individual cases. RESULTS: Overall 'PCR or VL or both' rate was 1.92% (95%
      CI=1.81-2.04%). Risk indicators for this complication were increasing age, male
      gender, presence of glaucoma, diabetic retinopathy, brunescent/white cataract, no
      fundal view/vitreous opacities, pseudo-exfoliation/phacodonesis, reducing pupil
      size, axial length > or = 26.0 mm, the use of the alpha-blocker doxazosin,
      inability to lie flat and trainee surgeons performing operations. Adjusted ORs
      for these variables are used to estimate overall composite risk across multiple
      risk indicators in the form of a predicted probability of PCR or VL or both.
      Predicted probability for this complication ranged from less than 0.75% to more
      than 75%, depending on risk profile of individual operations. CONCLUSIONS: Higher
      risk cases can be predicted, thus better informing the consent process and
      allowing surgeons to take appropriate precautions. Case-mix is a major
      determinant of the probability of an intraoperative complication. A simple
      composite risk estimation system has been developed.

PMID- 18327165
TI  - Suture fixation of dislocated endothelial grafts.
AB  - PURPOSE: To share the experience of suturing the displaced endothelial grafts in
      three patients who developed this complication following a posterior endothelial
      keratoplasty. METHODS: Prospective evaluation of three patients who underwent
      surgical revision by suture fixation for dislocated endothelial graft. The
      surgeries were performed immediately after noting the complication during the
      post-op visits and were followed up for 6 months. Assessments at follow-up visits
      include visual acuity, pachymetry, endothelial cell count, topography, and
      corneal slit-lamp digital photography. RESULTS: No significant postoperative
      complications were encountered in any of the three eyes after graft suturing. The
      vision was worse than hand movements in all, following the graft dislocation and
      this improved to an average of 20/50 at 6-month post-op. In two of the three eyes
      the endothelial cell count reduced from 2600 cells preoperatively to 1251 and 988
      cells, respectively. Mean topographic astigmatism after the suture removal was
      2.4 D. CONCLUSION: Suture fixation of early endothelial graft dislocation seems
      to be a good alternative in dislocated endothelial discs as it provides a good
      refractive and visual outcome, instead of converting it to a standard full
      thickness penetrating keratoplasty.

PMID- 18327166
TI  - Who does what and why?

PMID- 18327167
TI  - Direct contact.

PMID- 18327168
TI  - Bio-, eco- and nano-.

PMID- 18327169
TI  - Coping with treatment.

PMID- 18327170
TI  - George Cunningham.

PMID- 18327171
TI  - Asbestos dressing.

PMID- 18327172
TI  - Unusual tic.

PMID- 18327185
TI  - A Scandinavian tragedy.
AB  - This paper briefly reviews the logic surrounding the controversial banning of
      dental amalgam by the Norwegian government. The very small contribution from
      dentistry to environmental mercury pollution and the significant advantages of
      amalgam as a dental restorative are emphasised.

PMID- 18327186
TI  - Qualitative research in dentistry.
AB  - This paper is the first in a series of four that provides an overview of the key
      elements of qualitative research. In particular, it discusses issues such as what
      qualitative research is, when its use is appropriate, what it can offer dentistry
      and approaches to data collection and analysis. Where appropriate, examples of
      dental studies that have used qualitative methods are also provided for practical
      purposes.

PMID- 18327187
TI  - Factors contributing to the separation of endodontic files.
AB  - Cleaning and shaping of the root canal system is essential for successful
      endodontic treatment. However, despite improvements in file design and metal
      alloy, intracanal file separation is still a problematic incident and can occur
      without any visible signs or permanent deformation. Only a few studies have
      reported high success rates of fractured file removal using contemporary
      techniques. Conflicting results have been reported regarding the clinical
      significance of retaining separated files within root canals. An understanding of
      the mechanisms of, factors contributing to, file fracture is necessary to reduce
      the incidence of file separation within root canals. This article reviews the
      factors that are of utmost importance and in light of these, preventive
      procedures and measures are suggested.

PMID- 18327188
TI  - Nitrous oxide inhalation anaesthesia in the presence of intraocular gas can cause
      irreversible blindness.
AB  - Nitrous oxide inhalation sedation is frequently used in dental and other surgical
      procedures. We report the case of a patient with intraocular gas who developed
      sudden elevation in intraocular pressure and blindness as a result of nitrous
      oxide anaesthesia. All medical and dental personnel administering nitrous oxide
      inhalation should be aware that this is contraindicated in patients with
      intraocular gas.

PMID- 18327194
TI  - Better informed: an overview of health informatics.
AB  - Healthcare informatics is increasing in importance both for healthcare
      administrators and medical and dental practitioners. Governments across the
      developed world are initiating major national health IT programmes. At the same
      time, future best medical and dental practice will increasingly depend on
      computer-based support tools, although disagreement remains about the
      effectiveness of current support tools. Over the longer term, future informatics
      tools, combined with other medical and dental technology modalities, promise more
      adaptive, patient-focused and efficient healthcare and education for the
      practitioner and the patient.

PMID- 18327207
TI  - Dentistry with a difference: volunteering for 'Dental Project Peru'.
AB  - As a young dentist looking for new challenges and experiences, Mary Bussell
      decided to use her skills and training by volunteering for a dental charity
      working in Peru. Here she gives an account of her 'dental adventure'.

PMID- 18327208
TI  - Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas.
AB  - Definitive diagnosis of malignant mesothelioma in small specimens can be
      extremely difficult based on morphology alone. Homozygous deletion of 9p21, the
      locus harboring the p16 gene, has been reported as the most common genetic
      alteration in malignant mesotheliomas. Recent studies demonstrated that this
      alteration may be useful for differentiating benign from malignant mesothelial
      proliferations in cytology specimens. The aim of this study was to evaluate the
      diagnostic utility of homozygous deletion of 9p21 assessed by fluorescence in
      situ hybridization (FISH) in mesothelial proliferations involving serosal
      surfaces in paraffin-embedded tissue. p16 protein immunoexpression was also
      explored as a potential diagnostic aid. FISH analysis demonstrated homozygous
      deletion of the 9p21 locus in 35 of 52 cases (67%) of pleural mesothelioma and in
      5 of 20 cases of peritoneal mesothelioma (25%) (P<0.005). None of 40 cases of
      reactive pleural mesothelial proliferations showed p16 deletion (P<0.005). Loss
      of immunoexpression of p16 was observed in 71% of the peritoneal mesotheliomas,
      40% of the pleural malignant mesotheliomas and 15% of the reactive mesothelial
      cells. Homozygous deletion did not correlate with p16 protein expression in any
      of the studied groups. Our study suggests that 9p21 homozygous deletion assessed
      by FISH on paraffin-embedded tissue may be helpful for differentiating between
      malignant mesotheliomas and reactive mesothelial proliferations. A discrepancy
      between p16 protein expression and homozygous deletion suggests that other
      molecular mechanisms may play a role in p16 protein expression in mesothelial
      proliferations.

PMID- 18327209
TI  - Renal medullary carcinoma: rhabdoid features and the absence of INI1 expression
      as markers of aggressive behavior.
AB  - Renal medullary carcinoma is a rare, well-recognized highly aggressive tumor of
      varied histopathology, which occurs in young patients with sickle cell trait or
      disease. Rhabdoid elements, occasionally seen in high-grade renal tumors
      including renal medullary carcinoma, possibly represent a pathologic marker of
      aggressive behavior. INI1 (hSNF5/SMARCB1/BAF47) is a highly conserved factor in
      the ATP-dependent chromatin-modifying complex. Loss of this factor in mice
      results in aggressive rhabdoid tumors or lymphomas. In humans, the loss of INI1
      expression has been reported in pediatric renal rhabdoid tumors, central nervous
      system atypical teratoid/rhabdoid tumors and epithelioid sarcomas, a possible
      primary soft tissue rhabdoid tumor. This study compares five renal medullary
      carcinomas with 10 high-grade renal cell carcinomas (five with rhabdoid
      features), two urothelial carcinomas and two pediatric renal rhabdoid tumors. All
      five renal medullary carcinomas, irrespective of histopathology, showed complete
      loss of INI1 expression similar to that seen in pediatric renal rhabdoid tumors.
      In contrast, all renal cell carcinomas or urothelial carcinomas, including those
      with histological rhabdoid features, expressed INI1. Clinically, all five of the
      patients with renal medullary carcinoma and the two patients with rhabdoid tumors
      presented with extra-renal metastases at the time of diagnosis. This study
      demonstrates that renal medullary carcinoma and renal rhabdoid tumor share a
      common molecular/genetic alteration, which is closely linked to their aggressive
      biological behavior. However, the absence of INI1 expression is not necessarily
      predictive of rhabdoid histopathology but remains associated with aggressive
      behavior in renal medullary carcinoma.

PMID- 18327210
TI  - Cyclin D1 expression analysis in familial breast cancers may discriminate BRCAX
      from BRCA2-linked cases.
AB  - Most familial breast cancers arise in patients who tested negative for germline
      mutations in BRCA1 and BRCA2 genes (also referred to as BRCAX cases). Several
      studies aimed to define histopathological and molecular profiles characteristic
      of BRCA1, BRCA2 and BRCAX tumors have been performed. Major pathological and
      immunohistochemical differences have been reported in BRCA1 cancers compared to
      the other two groups, whereas less difference has been observed between BRCA2 and
      BRCAX cases. The aim of this study was to investigate the ability of selected
      tumor markers to discriminate BRCAX breast cancers from cancers arising in
      carriers of mutations in BRCA genes, and their usefulness in selecting familial
      cases in whom testing for such mutations is more likely to result uninformative.
      We carried out a morphological and immunohistochemical analysis on 22 BRCA1, 16
      BRCA2 and 33 BRCAX familial breast cancers. Age at first diagnosis, histological
      type and grade, and immunostaining for estrogen receptor (ER), progesterone
      receptor (PR), p53, HER2/Neu, E-cadherin and cyclin D1 were investigated. The
      occurrence of somatic mutations of the TP53 gene was also verified. BRCA1 tumors
      resulted clearly distinguishable from BRCAX cases, occurring at a younger age,
      being more frequently of higher grade, negative for ER, PR and cyclin D1
      expression and positive for p53 alterations. The predictive value of age at
      diagnosis, histological grade and PR expression was confirmed in a multivariable
      analysis. When comparing BRCA2 with BRCAX tumors, the only parameter that
      differed was cyclin D1, which was significantly overexpressed in BRCA2 cases both
      in the univariable and the multivariable analyses. If confirmed by further
      studies, our observations indicate that the investigation of cyclin D1 expression
      in familial breast cancer cases could be used, in conjunction with the analysis
      of other tumor markers preferentially associated with BRCA1 or BRCA2 tumors, to
      prioritize hereditary cases for mutation testing in BRCA genes.

PMID- 18327211
TI  - Altered eIF6 and Dicer expression is associated with clinicopathological features
      in ovarian serous carcinoma patients.
AB  - MicroRNAs are a group of small non-coding RNAs approximately 22 nucleotides in
      length. Recent work has shown differential expression of mature microRNAs in
      human cancers. Production and function of microRNAs require coordinated
      processing by proteins of the microRNA machinery. Dicer and Drosha (RNase III
      endonucleases) are essential components of the microRNA machinery. Recently, the
      ribosome anti-association factor eIF6 has also been found to have a role in
      microRNA-mediated post-transcriptional silencing. We characterized the
      alterations in the expression of genes encoding proteins of microRNA machinery in
      ovarian serous carcinoma. Protein expression of eIF6 and Dicer was quantified in
      a tissue microarray of 66 ovarian serous carcinomas. Dicer, Drosha and eIF6 mRNA
      expression was analysed using quantitative reverse transcription-PCR on an
      independent set of 50 formalin-fixed, paraffin-embedded ovarian serous carcinoma
      samples. Expression profiles of eIF6 and Dicer were correlated with
      clinicopathological and patient survival data. We provide definitive evidence
      that eIF6 and Dicer are both upregulated in a significant proportion of ovarian
      serous carcinomas and are associated with specific clinicopathological features,
      most notably low eIF6 expression being associated with reduced disease-free
      survival. The status of eIF6 and proteins of the microRNA machinery may help
      predict toxicity and susceptibility to future interfering RNA-based therapy.

PMID- 18327212
TI  - PAX3 expression in primary melanomas and nevi.
AB  - Melanoma is responsible for an estimated 62,000 new American cancer diagnoses and
      is projected to cause nearly 8000 deaths in 2008 alone. Although the histogenesis
      of the tumor is not well understood, it is thought to originate from a rare
      melanocyte stem cell that resides in the skin. The transcription factor PAX3 has
      a well-established role in the development of melanocytes during embryogenesis,
      and has recently been characterized as a molecular switch in the mature
      melanocyte. Based on this function, PAX3 promotes a melanocytic phenotype but
      blocks terminal differentiation. This mechanism may also contribute to the
      uncontrolled cell growth and loss of terminal differentiation in melanomas. Here,
      we find PAX3 expression in 8/8 melanoma cell lines. We also find that PAX3 is
      commonly expressed in primary melanoma samples (21/58) but significantly less
      frequently in benign pigmented lesions (9/75). Further analysis of our melanoma
      set revealed that PAX3 expression is strongly correlated with younger patients
      with low or no evidence of sun damage. Our data suggest that PAX3-expressing
      melanomas may be less environmentally dependent and more genetically linked.

PMID- 18327213
TI  - Off the rails.

PMID- 18327214
TI  - Cloned animals deemed safe to eat, but labeling issues loom.

PMID- 18327215
TI  - Recombinant thrombin approved.

PMID- 18327216
TI  - Genzyme and Isis strike megadeal.

PMID- 18327217
TI  - BiDil flops.

PMID- 18327218
TI  - Human embryos cloned.

PMID- 18327219
TI  - Start-ups weigh benefits of corporate incubators.

PMID- 18327220
TI  - Plant biotechs defect.

PMID- 18327221
TI  - Another inhaled insulin casualty.

PMID- 18327222
TI  - Investor malaise stalks UK, European biotech.

PMID- 18327223
TI  - 1000 Genomes project.

PMID- 18327224
TI  - HIV vaccine controversy.

PMID- 18327225
TI  - Tony Conner.

PMID- 18327226
TI  - Brazil surpasses US in new transgenic crop plantings.

PMID- 18327227
TI  - Vintage genetic engineering.

PMID- 18327228
TI  - Do amniotic fluid-derived stem cells differentiate into neurons in vitro?

PMID- 18327230
TI  - iPS cells and the politics of promise.

PMID- 18327231
TI  - The 20-year African biotech plan.

PMID- 18327232
TI  - BLOSUM62 miscalculations improve search performance.

PMID- 18327233
TI  - When biotech crosses borders.
AB  - Rapid action is needed to address loopholes in the international governance of
      self-dispersing genetically modified organisms (GMOs) purposefully released for
      the management of wild species and diseases.

PMID- 18327234
TI  - Chasing biotech across Europe.

PMID- 18327235
TI  - Monsanto Technology LLC v. Cargill: a matter of construction.

PMID- 18327237
TI  - Digital mRNA profiling.

PMID- 18327238
TI  - A toolkit for the cell's powerhouse.

PMID- 18327239
TI  - Synthetic genomes brought closer to life.

PMID- 18327240
TI  - Metabolic engineering delivers next-generation biofuels.

PMID- 18327241
TI  - Tiny tiles, tiny targets.

PMID- 18327243
TI  - What is principal component analysis?

PMID- 18327247
TI  - Developing China's homegrown biotechnology workforce.

PMID- 18327244
TI  - Minimum information specification for in situ hybridization and
      immunohistochemistry experiments (MISFISHIE).
AB  - One purpose of the biomedical literature is to report results in sufficient
      detail that the methods of data collection and analysis can be independently
      replicated and verified. Here we present reporting guidelines for gene expression
      localization experiments: the minimum information specification for in situ
      hybridization and immunohistochemistry experiments (MISFISHIE). MISFISHIE is
      modeled after the Minimum Information About a Microarray Experiment (MIAME)
      specification for microarray experiments. Both guidelines define what information
      should be reported without dictating a format for encoding that information.
      MISFISHIE describes six types of information to be provided for each experiment:
      experimental design, biomaterials and treatments, reporters, staining, imaging
      data and image characterizations. This specification has benefited the consortium
      within which it was developed and is expected to benefit the wider research
      community. We welcome feedback from the scientific community to help improve our
      proposal.

PMID- 18327249
TI  - Noninvasive in vivo imaging of pancreatic islet cell biology.
AB  - Advanced imaging techniques have become a valuable tool in the study of complex
      biological processes at the cellular level in biomedical research. Here, we
      introduce a new technical platform for noninvasive in vivo fluorescence imaging
      of pancreatic islets using the anterior chamber of the eye as a natural body
      window. Islets transplanted into the mouse eye engrafted on the iris, became
      vascularized, retained cellular composition, responded to stimulation and
      reverted diabetes. Laser-scanning microscopy allowed repetitive in vivo imaging
      of islet vascularization, beta cell function and death at cellular resolution.
      Our results thus establish the basis for noninvasive in vivo investigations of
      complex cellular processes, like beta cell stimulus-response coupling, which can
      be performed longitudinally under both physiological and pathological conditions.

PMID- 18327250
TI  - Following translation by single ribosomes one codon at a time.
AB  - We have followed individual ribosomes as they translate single messenger RNA
      hairpins tethered by the ends to optical tweezers. Here we reveal that
      translation occurs through successive translocation--and-pause cycles. The
      distribution of pause lengths, with a median of 2.8 s, indicates that at least
      two rate-determining processes control each pause. Each translocation step
      measures three bases--one codon-and occurs in less than 0.1 s. Analysis of the
      times required for translocation reveals, surprisingly, that there are three
      substeps in each step. Pause lengths, and thus the overall rate of translation,
      depend on the secondary structure of the mRNA; the applied force destabilizes
      secondary structure and decreases pause durations, but does not affect
      translocation times. Translocation and RNA unwinding are strictly coupled
      ribosomal functions.

PMID- 18327251
TI  - The NHL-domain protein Wech is crucial for the integrin-cytoskeleton link.
AB  - Integrin transmembrane receptors mediate cell adhesion through intracellular
      linker proteins that connect to the cytoskeleton. Of the numerous linker proteins
      identified, only a few, including Talin and Integrin-linked-kinase (ILK), are
      essential and evolutionarily conserved. The wech gene encodes a newly discovered
      and highly conserved regulator of integrin-mediated adhesion in Drosophila
      melanogaster. Embryos deficient in wech have very similar phenotypes to integrin
      null or Talin-null embryos, including muscle detachment from the body wall. The
      Wech protein contains a B-box zinc-finger and a coiled-coil domain, which is also
      found in RBCC/TRIM family members, and an NHL domain. In beta-integrin or Talin
      mutants, Wech is mislocalized, whereas ILK localization depends on Wech. We
      provide evidence that Wech interacts with the head domain of Talin and the kinase
      domain of ILK, and propose that Wech is required to connect both core proteins of
      the linker complex during embryonic muscle attachment. Both the NHL and the B
      box/coiled-coil domains of Wech are required for proper interaction with Talin
      and ILK. The single murine Wech orthologue is also colocalized with Talin and ILK
      in muscle tissue. We propose that Wech proteins are crucial and evolutionarily
      conserved regulators of the integrin-cytoskeleton link.

PMID- 18327252
TI  - Identification of small molecules rescuing fragile X syndrome phenotypes in
      Drosophila.
AB  - Fragile X syndrome is caused by the functional loss of the fragile X mental
      retardation 1 (FMR1) gene. Deletion of the FMR1 ortholog in Drosophila
      melanogaster (Fmr1) recapitulates many phenotypes associated with fragile X
      syndrome. We have discovered that Fmr1 mutant Drosophila die during development
      when reared on food containing increased levels of glutamate, which is consistent
      with the theory that FMR1 loss results in excess glutamate signaling. Using this
      lethal phenotype, we screened a chemical library of 2,000 compounds and
      identified nine molecules that rescued the lethality, including three that
      implicate the GABAergic inhibitory pathway. Indeed, GABA treatment rescued
      several known Fmr1 mutant phenotypes in flies, including mushroom bodies defects,
      excess Futsch translation and abnormal male courtship behavior. These data are
      consistent with GABAergic inhibition of the enhanced excitatory pathway in
      fragile X syndrome. In addition, our screen reveals that the muscarinic
      cholinergic receptors may have a role in fragile X syndrome in parallel to the
      GABAergic pathway. These results point to potential therapeutic approaches for
      treating fragile X syndrome.

PMID- 18327253
TI  - Neural correlates of perceptual learning in a sensory-motor, but not a sensory,
      cortical area.
AB  - This study aimed to identify neural mechanisms that underlie perceptual learning
      in a visual-discrimination task. We trained two monkeys (Macaca mulatta) to
      determine the direction of visual motion while we recorded from their middle
      temporal area (MT), which in trained monkeys represents motion information that
      is used to solve the task, and lateral intraparietal area (LIP), which represents
      the transformation of motion information into a saccadic choice. During training,
      improved behavioral sensitivity to weak motion signals was accompanied by changes
      in motion-driven responses of neurons in LIP, but not in MT. The time course and
      magnitude of the changes in LIP correlated with the changes in behavioral
      sensitivity throughout training. Thus, for this task, perceptual learning does
      not appear to involve improvements in how sensory information is represented in
      the brain, but rather how the sensory representation is interpreted to form the
      decision that guides behavior.

PMID- 18327254
TI  - Plexin-A2 and its ligand, Sema6A, control nucleus-centrosome coupling in
      migrating granule cells.
AB  - During their migration, cerebellar granule cells switch from a tangential to a
      radial mode of migration. We have previously demonstrated that this involves the
      transmembrane semaphorin Sema6A. We show here that plexin-A2 is the receptor that
      controls Sema6A function in migrating granule cells. In plexin-A2-deficient
      (Plxna2(-/-)) mice, which were generated by homologous recombination, many
      granule cells remained in the molecular layer, as we saw in Sema6a mutants. A
      similar phenotype was observed in mutant mice that were generated by mutagenesis
      with N-ethyl-N-nitrosourea and had a single amino-acid substitution in the
      semaphorin domain of plexin-A2. We found that this mutation abolished the ability
      of Sema6A to bind to plexin-A2. Mouse chimera studies further suggested that
      plexin-A2 acts in a cell-autonomous manner. We also provide genetic evidence for
      a ligand-receptor relationship between Sema6A and plexin-A2 in this system. Using
      time-lapse video microscopy, we found that centrosome-nucleus coupling and
      coordinated motility were strongly perturbed in Sema6a(-/-) and Plxna2(-/-)
      granule cells. This suggests that semaphorin-plexin signaling modulates cell
      migration by controlling centrosome positioning.

PMID- 18327255
TI  - Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet
      Biedl syndrome.
AB  - Meckel-Gruber syndrome (MKS) is a genetically heterogeneous, neonatally lethal
      malformation and the most common form of syndromic neural tube defect (NTD). To
      date, several MKS-associated genes have been identified whose protein products
      affect ciliary function. Here we show that mutations in MKS1, MKS3 and CEP290
      (also known as NPHP6) either can cause Bardet-Biedl syndrome (BBS) or may have a
      potential epistatic effect on mutations in known BBS-associated loci. Five of six
      families with both MKS1 and BBS mutations manifested seizures, a feature that is
      not a typical component of either syndrome. Functional studies in zebrafish
      showed that mks1 is necessary for gastrulation movements and that it interacts
      genetically with known bbs genes. Similarly, we found two families with missense
      or splice mutations in MKS3, in one of which the affected individual also bears a
      homozygous nonsense mutation in CEP290 that is likely to truncate the C terminus
      of the protein. These data extend the genetic stratification of ciliopathies and
      suggest that BBS and MKS, although distinct clinically, are allelic forms of the
      same molecular spectrum.

PMID- 18327256
TI  - SLC2A9 influences uric acid concentrations with pronounced sex-specific effects.
AB  - Serum uric acid concentrations are correlated with gout and clinical entities
      such as cardiovascular disease and diabetes. In the genome-wide association study
      KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n =
      1,644), the most significant SNPs associated with uric acid concentrations mapped
      within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter
      (effects: -0.23 to -0.36 mg/dl per copy of the minor allele). We replicated these
      findings in three independent samples from Germany (KORA S4 and SHIP (Study of
      Health in Pomerania)) and Austria (SAPHIR; Salzburg Atherosclerosis Prevention
      Program in Subjects at High Individual Risk), with P values ranging from 1.2 x
      10(-8) to 1.0 x 10(-32). Analysis of whole blood RNA expression profiles from a
      KORA F3 500K subgroup (n = 117) showed a significant association between the
      SLC2A9 isoform 2 and urate concentrations. The SLC2A9 genotypes also showed
      significant association with self-reported gout. The proportion of the variance
      of serum uric acid concentrations explained by genotypes was about 1.2% in men
      and 6% in women, and the percentage accounted for by expression levels was 3.5%
      in men and 15% in women.

PMID- 18327257
TI  - SLC2A9 is a newly identified urate transporter influencing serum urate
      concentration, urate excretion and gout.
AB  - Uric acid is the end product of purine metabolism in humans and great apes, which
      have lost hepatic uricase activity, leading to uniquely high serum uric acid
      concentrations (200-500 microM) compared with other mammals (3-120 microM). About
      70% of daily urate disposal occurs via the kidneys, and in 5-25% of the human
      population, impaired renal excretion leads to hyperuricemia. About 10% of people
      with hyperuricemia develop gout, an inflammatory arthritis that results from
      deposition of monosodium urate crystals in the joint. We have identified genetic
      variants within a transporter gene, SLC2A9, that explain 1.7-5.3% of the variance
      in serum uric acid concentrations, following a genome-wide association scan in a
      Croatian population sample. SLC2A9 variants were also associated with low
      fractional excretion of uric acid and/or gout in UK, Croatian and German
      population samples. SLC2A9 is a known fructose transporter, and we now show that
      it has strong uric acid transport activity in Xenopus laevis oocytes.

PMID- 18327258
TI  - THM1 negatively modulates mouse sonic hedgehog signal transduction and affects
      retrograde intraflagellar transport in cilia.
AB  - Characterization of previously described intraflagellar transport (IFT) mouse
      mutants has led to the proposition that normal primary cilia are required for
      mammalian cells to respond to the sonic hedgehog (SHH) signal. Here we describe
      an N-ethyl-N-nitrosourea-induced mutant mouse, alien (aln), which has abnormal
      primary cilia and shows overactivation of the SHH pathway. The aln locus encodes
      a novel protein, THM1 (tetratricopeptide repeat-containing hedgehog modulator-1),
      which localizes to cilia. aln-mutant cilia have bulb-like structures at their
      tips in which IFT proteins (such as IFT88) are sequestered, characteristic of
      Chlamydomonas reinhardtii and Caenorhabditis elegans retrograde IFT mutants. RNA
      interference knockdown of Ttc21b (which we call Thm1 and which encodes THM1) in
      mouse inner medullary collecting duct cells expressing an IFT88-enhanced yellow
      fluorescent protein fusion recapitulated the aln-mutant cilial phenotype, and
      live imaging of these cells revealed impaired retrograde IFT. In contrast to
      previously described IFT mutants, Smoothened and full-length glioblastoma (GLI)
      proteins localize to aln-mutant cilia. We hypothesize that the aln retrograde IFT
      defect causes sequestration of IFT proteins in aln-mutant cilia and leads to the
      overactivated SHH signaling phenotype. Specifically, the aln mutation uncouples
      the roles of anterograde and retrograde transport in SHH signaling, suggesting
      that anterograde IFT is required for GLI activation and that retrograde IFT
      modulates this event.

PMID- 18327259
TI  - Lymphoproliferative disease and autoimmunity in mice with increased miR-17-92
      expression in lymphocytes.
AB  - The genomic region encoding the miR-17-92 microRNA (miRNA) cluster is often
      amplified in lymphoma and other cancers, and cancer cells carrying this
      amplification have higher expression of miRNA in this cluster. Retroviral
      expression of miR-17-92 accelerates c-Myc-induced lymphoma development, but
      precisely how higher expression of miR-17-92 promotes lymphomagenesis remains
      unclear. Here we generated mice with higher expression of miR-17-92 in
      lymphocytes. These mice developed lymphoproliferative disease and autoimmunity
      and died prematurely. Lymphocytes from these mice showed more proliferation and
      less activation-induced cell death. The miR-17-92 miRNA suppressed expression of
      the tumor suppressor PTEN and the proapoptotic protein Bim. This mechanism
      probably contributed to the lymphoproliferative disease and autoimmunity of miR
      17-92-transgenic mice and contributes to lymphoma development in patients with
      amplifications of the miR-17-92 coding region.

PMID- 18327260
TI  - Dual functions for the endoplasmic reticulum calcium sensors STIM1 and STIM2 in T
      cell activation and tolerance.
AB  - Store-operated Ca2+ entry through calcium release-activated calcium channels is
      the chief mechanism for increasing intracellular Ca2+ in immune cells. Here we
      show that mouse T cells and fibroblasts lacking the calcium sensor STIM1 had
      severely impaired store-operated Ca2+ influx, whereas deficiency in the calcium
      sensor STIM2 had a smaller effect. However, T cells lacking either STIM1 or STIM2
      had much less cytokine production and nuclear translocation of the transcription
      factor NFAT. T cell-specific ablation of both STIM1 and STIM2 resulted in a
      notable lymphoproliferative phenotype and a selective decrease in regulatory T
      cell numbers. We conclude that both STIM1 and STIM2 promote store-operated Ca2+
      entry into T cells and fibroblasts and that STIM proteins are required for the
      development and function of regulatory T cells.

PMID- 18327261
TI  - Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry
      of lymphocytes into secondary lymphoid organs.
AB  - The extracellular lysophospholipase D autotaxin (ATX) and its product,
      lysophosphatidic acid, have diverse functions in development and cancer, but
      little is known about their functions in the immune system. Here we found that
      ATX had high expression in the high endothelial venules of lymphoid organs and
      was secreted. Chemokine-activated lymphocytes expressed receptors with enhanced
      affinity for ATX, which provides a mechanism for targeting the secreted ATX to
      lymphocytes undergoing recruitment. Lysophosphatidic acid induced chemokinesis in
      T cells. Intravenous injection of enzymatically inactive ATX attenuated the
      homing of T cells to lymphoid tissues, probably through competition with
      endogenous ATX and exertion of a dominant negative effect. Our results support
      the idea of a new and general step in the homing cascade in which the ectoenzyme
      ATX facilitates the entry of lymphocytes into lymphoid organs.

PMID- 18327262
TI  - Ledge-flow-controlled catalyst interface dynamics during Si nanowire growth.
AB  - Self-assembled nanowires offer the prospect of accurate and scalable device
      engineering at an atomistic scale for applications in electronics, photonics and
      biology. However, deterministic nanowire growth and the control of dopant
      profiles and heterostructures are limited by an incomplete understanding of the
      role of commonly used catalysts and specifically of their interface dynamics.
      Although catalytic chemical vapour deposition of nanowires below the eutectic
      temperature has been demonstrated in many semiconductor-catalyst systems, growth
      from solid catalysts is still disputed and the overall mechanism is largely
      unresolved. Here, we present a video-rate environmental transmission electron
      microscopy study of Si nanowire formation from Pd silicide crystals under
      disilane exposure. A Si crystal nucleus forms by phase separation, as observed
      for the liquid Au-Si system, which we use as a comparative benchmark. The
      dominant coherent Pd silicide/Si growth interface subsequently advances by
      lateral propagation of ledges, driven by catalytic dissociation of disilane and
      coupled Pd and Si diffusion. Our results establish an atomistic framework for
      nanowire assembly from solid catalysts, relevant also to their contact formation.

PMID- 18327263
TI  - Coordination-dependent surface atomic contraction in nanocrystals revealed by
      coherent diffraction.
AB  - Surface atoms have fewer interatomic bonds than those in the bulk that they often
      relax and reconstruct on extended two-dimensional surfaces. Far less is known
      about the surface structures of nanocrystals. Here, we show that coherent
      diffraction patterns recorded from individual nanocrystals are very sensitive to
      the atomic structure of nanocrystal surfaces. Nanocrystals of Au of 3-5 nm in
      diameter were studied by examining diffraction intensity oscillations around the
      Bragg peaks. Both results obtained from modelling the experimental data and
      molecular dynamics simulations strongly suggest inhomogeneous relaxations,
      involving large out-of-plane bond length contractions for the edge atoms
      (approximately 0.2 A); a significant contraction (approximately 0.13 A) for {100}
      surface atoms; and a much smaller contraction (approximately 0.05 A) for atoms in
      the middle of the {111} facets. These results denote a coordination/facet
      dependence that markedly differentiates the structural dynamics of nanocrystals
      from bulk crystalline surfaces.

PMID- 18327264
TI  - Identification of cross-linked peptides from large sequence databases.
AB  - We describe a method to identify cross-linked peptides from complex samples and
      large protein sequence databases by combining isotopically tagged cross-linkers,
      chromatographic enrichment, targeted proteomics and a new search engine called
      xQuest. This software reduces the search space by an upstream candidate-peptide
      search before the recombination step. We showed that xQuest can identify cross
      linked peptides from a total Escherichia coli lysate with an unrestricted
      database search.

PMID- 18327265
TI  - High-resolution, high-throughput SNP mapping in Drosophila melanogaster.
AB  - Single nucleotide polymorphisms (SNPs) are useful markers for genetic mapping
      experiments in model organisms. Here we report the establishment of a high
      density SNP map and high-throughput genotyping assays for Drosophila
      melanogaster. Our map comprises 27,367 SNPs in common laboratory Drosophila
      stocks. These SNPs were clustered within 2,238 amplifiable markers at an average
      density of 1 marker every 50.3 kb, or 6.3 genes. We have also constructed a set
      of 62 Drosophila stocks, each of which facilitates the generation of recombinants
      within a defined genetic interval of 1-2 Mb. For flexible, high-throughput SNP
      genotyping, we used fluorescent tag-array mini-sequencing (TAMS) assays. We
      designed and validated TAMS assays for 293 SNPs at an average resolution of 391.3
      kb, and demonstrated the utility of these tools by rapidly mapping 14 mutations
      that disrupt embryonic muscle patterning. These resources enable high-resolution
      high-throughput genetic mapping in Drosophila.

PMID- 18327266
TI  - Genetic control of neuronal activity in mice conditionally expressing TRPV1.
AB  - Here we describe a knock-in mouse model for Cre-loxP-based conditional expression
      of TRPV1 in central nervous system neurons. Expression of Cre recombinase using
      biolistics, lentivirus or genetic intercrosses triggered heterologous expression
      of TRPV1 in a cell-specific manner. Application of the TRPV1 ligand capsaicin
      induced strong inward currents, triggered action potentials and activated
      stereotyped behaviors, allowing cell type-specific chemical genetic control of
      neuronal activity in vitro and in vivo.

PMID- 18327267
TI  - Subversion of Toll-like receptor signaling by a unique family of bacterial
      Toll/interleukin-1 receptor domain-containing proteins.
AB  - Pathogenic microbes have evolved sophisticated molecular strategies to subvert
      host defenses. Here we show that virulent bacteria interfere directly with Toll
      like receptor (TLR) function by secreting inhibitory homologs of the
      Toll/interleukin-1 receptor (TIR) domain. Genes encoding TIR domain containing
      proteins (Tcps) were identified in Escherichia coli CFT073 (TcpC) and Brucella
      melitensis (TcpB). We found that TcpC is common in the most virulent
      uropathogenic E. coli strains and promotes bacterial survival and kidney
      pathology in vivo. In silico analysis predicted significant tertiary structure
      homology to the TIR domain of human TLR1, and we show that the Tcps impede TLR
      signaling through the myeloid differentiation factor 88 (MyD88) adaptor protein,
      owing to direct binding of Tcps to MyD88. Tcps represent a new class of virulence
      factors that act by inhibiting TLR- and MyD88-specific signaling, thus
      suppressing innate immunity and increasing virulence.

PMID- 18327268
TI  - ATAC is a double histone acetyltransferase complex that stimulates nucleosome
      sliding.
AB  - The Ada2a-containing (ATAC) complex is an essential Drosophila melanogaster
      histone acetyltransferase (HAT) complex that contains the transcriptional
      cofactors Gcn5 (KAT2), Ada3, Ada2a, Atac1 and Hcf. We have analyzed the complex
      by MudPIT (multidimensional protein identification technology) and found eight
      previously unidentified subunits. These include the WD40 repeat protein WDS, the
      PHD and HAT domain protein CG10414 (herein renamed Atac2/KAT14), the YEATS family
      member D12, the histone fold proteins CHRAC14 and NC2beta, CG30390, CG32343
      (Atac3) and CG10238. The presence of CG10414 (Atac2) suggests that it acts as a
      second acetyltransferase enzyme in ATAC in addition to Gcn5. Indeed, recombinant
      Atac2 displays HAT activity in vitro with a preference for acetylating histone
      H4, and mutation of Atac2 abrogated H4 lysine 16 acetylation in D. melanogaster
      embryos. Furthermore, although ATAC does not show nucleosome-remodeling activity
      itself, it stimulates nucleosome sliding by the ISWI, SWI-SNF and RSC complexes.

PMID- 18327269
TI  - Basis of altered RNA-binding specificity by PUF proteins revealed by crystal
      structures of yeast Puf4p.
AB  - Pumilio/FBF (PUF) family proteins are found in eukaryotic organisms and regulate
      gene expression post-transcriptionally by binding to sequences in the 3'
      untranslated region of target transcripts. PUF proteins contain an RNA binding
      domain that typically comprises eight alpha-helical repeats, each of which
      recognizes one RNA base. Some PUF proteins, including yeast Puf4p, have altered
      RNA binding specificity and use their eight repeats to bind to RNA sequences with
      nine or ten bases. Here we report the crystal structures of Puf4p alone and in
      complex with a 9-nucleotide (nt) target RNA sequence, revealing that Puf4p
      accommodates an 'extra' nucleotide by modest adaptations allowing one base to be
      turned away from the RNA binding surface. Using structural information and
      sequence comparisons, we created a mutant Puf4p protein that preferentially binds
      to an 8-nt target RNA sequence over a 9-nt sequence and restores binding of each
      protein repeat to one RNA base.

PMID- 18327270
TI  - Bacterial strategies to overcome insect defences.
AB  - Recent genetic and molecular analyses have revealed how several strategies enable
      bacteria to persist and overcome insect immune defences. Genetic and genomic
      tools that can be used with Drosophila melanogaster have enabled the
      characterization of the pathways that are used by insects to detect bacterial
      invaders and combat infection. Conservation of bacterial virulence factors and
      insect immune repertoires indicates that there are common strategies of host
      invasion and pathogen eradication. Long-term interactions of bacteria with
      insects might ensure efficient dissemination of pathogens to other hosts,
      including humans.

PMID- 18327271
TI  - Teichoic acids and related cell-wall glycopolymers in Gram-positive physiology
      and host interactions.
AB  - Most Gram-positive bacteria incorporate membrane- or peptidoglycan-attached
      carbohydrate-based polymers into their cell envelopes. Such cell-wall
      glycopolymers (CWGs) often have highly variable structures and have crucial roles
      in protecting, connecting and controlling the major envelope constituents.
      Further important roles of CWGs in host-cell adhesion, inflammation and immune
      activation have also been described in recent years. Identifying and harnessing
      highly conserved or species-specific structural features of CWGs offers excellent
      opportunities for developing new antibiotics, vaccines and diagnostics for use in
      the fight against severe infectious diseases, such as sepsis, pneumonia, anthrax
      and tuberculosis.

PMID- 18327272
TI  - Achromatic system for a twisted alignment liquid crystal wavefront corrector.
AB  - A twisted nematic liquid crystal wavefront corrector (TN-LCWFC) partially
      modulates the incident polarized light. A blazed grating may be preapplied on the
      TN-LCWFC to filter the unmodulated light for the purpose of stable adaptive
      correction. However, for broadband light, the dispersion of the blazed grating
      affects the image resolution. An achromatic method is presented to eliminate the
      dispersion of the blazed grating. Based on a prism model, we analyze the
      achromatic principle. An achromatic system with a conjugated blazed grating and
      an achromatic lens is given to eliminate the dispersion. An experiment was done
      with two transmitted blazed gratings so as to validate our method. Finally, a
      liquid crystal spatial light modulator was used as a conjugated grating to
      eliminate the dispersion of the blazed grating in an adaptive optics system. The
      results showed that the dispersion was partially compensated, and a resolvable
      image was achieved with a 600-700 nm wave band.

PMID- 18327273
TI  - One-dimensional barcode reading: an information theoretic approach.
AB  - In the convergence context of identification technology and information-data
      transmission, the barcode found its place as the simplest and the most pervasive
      solution for new uses, especially within mobile commerce, bringing youth to this
      long-lived technology. From a communication theory point of view, a barcode is a
      singular coding based on a graphical representation of the information to be
      transmitted. We present an information theoretic approach for 1D image-based
      barcode reading analysis. With a barcode facing the camera, distortions and
      acquisition are modeled as a communication channel. The performance of the system
      is evaluated by means of the average mutual information quantity. On the basis of
      this theoretical criterion for a reliable transmission, we introduce two new
      measures: the theoretical depth of field and the theoretical resolution.
      Simulations illustrate the gain of this approach.

PMID- 18327274
TI  - Impulse response solution to the three-dimensional vector radiative transfer
      equation in atmosphere-ocean systems. I. Monte Carlo method.
AB  - We have developed a powerful 3D Monte Carlo code, as part of the Radiance in a
      Dynamic Ocean (RaDyO) project, which can compute the complete effective Mueller
      matrix at any detector position in a completely inhomogeneous turbid medium, in
      particular, a coupled atmosphere-ocean system. The light source can be either
      passive or active. If the light source is a beam of light, the effective Mueller
      matrix can be viewed as the complete impulse response Green matrix for the turbid
      medium. The impulse response Green matrix gives us an insightful way to see how
      each region of a turbid medium affects every other region. The present code is
      validated with the multicomponent approach for a plane-parallel system and the
      spherical harmonic discrete ordinate method for the 3D scalar radiative transfer
      system. Furthermore, the impulse response relation for a box-type cloud model is
      studied. This 3D Monte Carlo code will be used to generate impulse response Green
      matrices for the atmosphere and ocean, which act as inputs to a hybrid matrix
      operator-Monte Carlo method. The hybrid matrix operator-Monte Carlo method will
      be presented in part II of this paper.

PMID- 18327275
TI  - Use of retinal nerve fiber layer birefringence as an addition to absorption in
      retinal scanning for biometric purposes.
AB  - We built a device sensitive to the birefringence of the retinal nerve fiber layer
      for biometric purposes. A circle of 20 degrees diameter on the retina was scanned
      around the optic disk with a spot of light from a 785 nm laser diode. The
      nonbirefringent blood vessels indenting or displacing the retinal nerve fiber
      layer were seen as "blips" in the measured birefringence-derived signal. For
      comparison, the reflection-absorption signature of the blood vessel pattern in
      the scanned circle was also measured. The birefringence-derived signal proved to
      add useful information to the reflectance-absorption signature for retinal
      biometric scanning.

PMID- 18327276
TI  - Effect of beam sizes on the amplitude and phase of photothermal deflection
      signals for both uniform and nonuniform heating.
AB  - A detailed theoretical treatment of a one- (1D) and three-dimensional (3D)
      photothermal deflection (PTD) technique is presented. Important effects of the
      probe beam size occur in PTD experiments when the radius of this beam is of the
      order of magnitude of the thermal diffusion length. The calculation of this
      effect is checked by experiments in paraffin oil at low modulation frequency as
      well as for 1D and for 3D. In this last case, we have considered two kinds of
      deflection: normal and transverse, and we have studied their variation for
      different values of the pump beam radius. The coincidence between theoretical and
      experimental curves confirms the validity of our theoretical model.

PMID- 18327277
TI  - Impulse response solution to the three-dimensional vector radiative transfer
      equation in atmosphere-ocean systems. II. The hybrid matrix operator--Monte Carlo
      method.
AB  - A hybrid method is developed to solve the vector radiative transfer equation
      (VRTE) in a three-dimensional atmosphere-ocean system (AOS). The system is
      divided into three parts: the atmosphere, the dielectric interface, and the
      ocean. The Monte Carlo method is employed to calculate the impulse response
      functions (Green functions) for the atmosphere and ocean. The impulse response
      function of the dielectric interface is calculated by the Fresnel formulas. The
      matrix operator method is then used to couple these impulse response functions to
      obtain the vector radiation field for the AOS. The primary advantage of this
      hybrid method is that it solves the VRTE efficiently in an AOS with different
      dielectric interfaces while keeping the same atmospheric and oceanic conditions.
      For the first time, we present the downward radiance field in an ocean with a
      sinusoidal ocean wave.

PMID- 18327278
TI  - Chromatic effects of the atmosphere on astronomical adaptive optics.
AB  - The atmosphere introduces chromatic errors that may limit the performance of
      adaptive optics (AO) systems on large telescopes. Various aspects of this problem
      have been considered in the literature over the past two decades. It is necessary
      to revisit this problem in order to examine the effect on currently planned
      systems, including very high-order AO on current 8-10 m class telescopes and on
      future 30-42 m extremely large telescopes. We review the literature on chromatic
      effects and combine an analysis of all effects in one place. We examine
      implications for AO and point out some effects that should be taken into account
      in the design of future systems. In particular we show that attention should be
      paid to chromatic pupil shifts, which may arise in components such as atmospheric
      dispersion compensators.

PMID- 18327279
TI  - One- and two-dimensional single-mode differential fiber-optic displacement sensor
      for submillimeter measurements.
AB  - Using the overlap integral method and the Gaussian approximation for the single
      mode fiber-optic field, the working principle of one- and two-dimensional
      differential fiber-optic displacement sensors for submillimeter measurements is
      demonstrated. The sensors consist of one emitting fiber and two or three
      receiving fibers, respectively, for the one- and two-dimensional sensors. Sensor
      responses are intrinsically linear over a wide range of travels. Moreover, for
      the two-dimensional sensor, each axis of displacement can be measured
      independently. Sensor responses are simulated experimentally using a highly
      precise robot. Linearity, travel, and sensitivity are characterized for the
      different gap distance between the emitting and receiving fibers. A design chart
      that includes nonlinearity error, travel, sensitivity, and gap is finally
      proposed.

PMID- 18327280
TI  - Absolute linearity characterization of lock-in amplifiers.
AB  - In applications where low signal-to-noise ratios are encountered, the use of
      phase-sensitive detection (PSD) is highly advantageous and is applied widely.
      However, the characteristics of lock-in amplifiers that utilize the PSD
      technique, such as the linearity of the output and the gain of these instruments,
      have not been extensively evaluated. The author proposes a method for measuring
      the linearity characteristics of lock-in amplifiers and describes how this method
      was used to measure the linearity factor of three nominally identical
      commercially available digital lock-in amplifiers. The results of this study show
      that the linearity factor of these lock-in amplifiers can deviate from unity by
      more than 0.1% over a factor of 2 change in output. Moreover, the linearity
      characteristics of these lock-in amplifiers vary from one instrument to the next.
      The linearity characteristics were shown to be independent of the reference
      frequency, the time constant, and the temporal profile of the signal being
      analyzed. However, they were found to be dependent on the sensitivity settings of
      these instruments. The linearity characteristics of these instruments were
      observed not to change with time. This implies that, where the uncertainty
      contribution due to the nonlinearity of a lock-in amplifier is significant, the
      nonlinearity can be evaluated by using the method described in this article and
      can be used to apply corrections.

PMID- 18327281
TI  - Frequency stabilization of a 1.3 microm laser diode using double resonance
      optical pumping in the 5P 3/2-6S 1/2 transition of Rb atoms.
AB  - The frequency stabilization of a laser diode in the 1.3 microm region using
      double resonance optical pumping (DROP) spectrum in the 5P(3/2)-6S(1/2)
      transition of (87)Rb atoms is demonstrated. The signal-to-noise ratio of the DROP
      spectrum is approximately ten times higher than that of the previous optical
      optical double resonance spectrum. The spectral linewidth of the DROP measures
      8.4 MHz. When the frequency of a 1.367 microm laser diode is stabilized to the
      DROP spectrum, the frequency stability is 9 x 10(-12) after 100 s. Also, the
      wavelength of the frequency-stabilized laser locked to the 5P(3/2)-6S(1/2)
      transition using a wavelength meter is measured.

PMID- 18327282
TI  - Reflection coefficients of p- and s-polarized light by a quarter-wave layer:
      explicit expressions and application to beam splitters.
AB  - The complex-amplitude reflection coefficients of p- and s-polarized light by a
      transparent freestanding, embedded, or deposited quarter-wave layer (QWL) are
      derived as explicit functions of the angle of incidence and layer refractive
      index. This provides the basis for the design of 50%-50% beam splitters for
      incident s-polarized or unpolarized light that use a high-index (e.g., TiO2 or
      Ge) QWL embedded in a glass cube in the visible and near infrared spectral range.
      These simple devices have good angular and spectral response and are insensitive
      to small film thickness errors to the first order.

PMID- 18327283
TI  - Polarization mode dispersion measurement based on continuous polarization
      modulation.
AB  - A novel technique is proposed for measurement of the group delay (GD) and the
      differential group delay (DGD) of optical material, components, and fiber. This
      new method is based on continuous polarization modulation of the stimulus optical
      field as opposed to sequential polarization state switching used in the
      traditional phase shift method. A new complete derivation of the phase shift
      method, based on the modified Jones calculus of elementary matrices, is
      presented. The derivation reveals that the phase shift measurement actually
      depends on all eight elementary parameters that represent DGD and optical
      frequency derivatives of polarization-dependent loss (PDL). Thus, the new
      expression for the phase shift includes the combined effect of PDL and DGD. The
      proposed method is evaluated by measuring a section of polarization-maintaining
      fiber and a 50 km length of single-mode fiber over a wavelength range from 1530
      to 1610 nm. Measurements of DGD in a long single-mode fiber are shown to be
      highly insensitive to environmentally induced GD drift.

PMID- 18327284
TI  - Characterization of optical waveguides in YbVO4 crystals formed by 3.0 MeV oxygen
      ion implantation.
AB  - We report optical planar waveguide formation in vanadate laser crystals YbVO(4)
      by oxygen ion implantation at an energy of 3.0 MeV and doses from 5 x 10(13) to 2
      x 10(15) ions/cm(2) at room temperature. Positive changes of the ordinary
      refractive indices occur in the implanted regions, which define a waveguide
      structure in the near surface. The relationship between refractive index changes
      and doses is presented. Waveguide modes were measured at wavelengths of 633 and
      1539 nm, respectively. The magnified field pattern of the propagation light in
      the annealed waveguide was captured and studied by an end-coupling method. The
      refractive index profiles were reconstructed by the reflectivity calculation
      method.

PMID- 18327285
TI  - Cryogenic optical measurements of 12-segment-bonded carbon-fiber-reinforced
      silicon carbide composite mirror with support mechanism.
AB  - A 720 mm diameter 12-segment-bonded carbon-fiber-reinforced silicon carbide
      (C/SiC) composite mirror has been fabricated and tested at cryogenic
      temperatures. Interferometric measurements show significant cryogenic deformation
      of the C/SiC composite mirror, which is well reproduced by a model analysis with
      measured properties of the bonded segments. It is concluded that the deformation
      is due mostly to variation in coefficients of thermal expansion among segments.
      In parallel, a 4-degree-of-freedom ball-bearing support mechanism has been
      developed for cryogenic applications. The C/SiC composite mirror was mounted on
      an aluminum base plate with the support mechanism and tested again. Cryogenic
      deformation of the mirror attributed to thermal contraction of the aluminum base
      plate via the support mechanism is highly reduced by the support, confirming that
      the newly developed support mechanism is promising for its future application to
      large-aperture cooled space telescopes.

PMID- 18327286
TI  - Characterization of a high-brilliance soft x-ray laser at 13.9 nm by use of an
      oscillator-amplifier configuration.
AB  - We have improved a highly coherent x-ray laser at 13.9 nm using an oscillator
      amplifier configuration. To improve a high-brilliance x-ray laser, we adopted
      traveling wave pumping for the amplifier target and rotated the amplifier target
      3-4 mrad in the counterclockwise direction. Thereby, a seed x-ray laser can be
      amplified by medium plasma of the amplifier target with a high gain coefficient.
      The amplified x-ray laser has the output energy of approximately 1.3 microJ,
      corresponding to a large photon flux of 6.5 x 10(10) photons/pulse and a high
      peak brilliance of 5 x 10(26) photons/(s x mm(2) x mrad(2) x 0.01% bandwidth).

PMID- 18327287
TI  - Analytical determination of reflection-peak wavelengths of chirped sampled fiber
      Bragg gratings.
AB  - An analytical expression for calculating the position of the reflection-peak
      wavelength of a chirped sampled fiber Bragg grating (C-SFBG) is obtained for what
      is believed to be the first time. Using Fourier theory, the chirped sampling
      function of the C-SFBG is expanded, and an equivalent local Bragg period is then
      obtained to derive the expression of the peak wavelength. The calculated results
      based on the expression are in excellent agreement with the numerical reflection
      spectra obtained by the conventional transfer-matrix method.

PMID- 18327288
TI  - New generation photon-counting cameras: algol and CPNG.
AB  - Algol and Comptage de Photons Nouvelle Generation (CPNG) are new generation
      photon counting cameras developed for high angular resolution in the visible by
      means of optical aperture synthesis and speckle interferometry and for photon
      noise limited fast imaging of biological targets. They are intensified CCDs. They
      have been built to benefit from improvements in photonic commercial components,
      sensitivity, and personal computer workstations processing power. We present how
      we achieve optimal performances (sensitivity and spatiotemporal resolution) by
      the combination of proper optical and electronics design, and real-time
      elaborated data processing. The number of pixels is 532 x 516 and 1024(2) read at
      a frame rate of 262 and 100 Hz for CPNG and Algol, respectively. The dark current
      is very low: 5.5 x 10(-4) e(-) .pixel(-1). s(-1). The saturation flux is
      approximately 7 photon events /pixel/s. Quantum efficiencies reach up to 36% and
      26% in the visible with the GaAsP photocathodes and in the red with the GaAs
      ones, respectively, thanks to the sensitivity of the photocathodes and to the
      photon centroiding algorithm; they are likely the highest values reported for
      intensified CCDs.

PMID- 18327289
TI  - Obscuration size dependence of hot image in laser beam through a Kerr medium slab
      with gain and loss.
AB  - We present a study of the formation of a hot image in an intense laser beam
      through a slab of Kerr medium with gain and loss, beyond the thin-medium
      approximation, to especially disclose the dependence of the hot image on the size
      of obscuration. Based on the angular spectrum description of light propagation
      and the mean-field approximation we obtain the expression for intensity of the
      hot image, which clearly shows the dependence of intensity of the hot image on
      the size of obscuration. It is shown that, as the size of obscuration increases,
      the intensity of the corresponding hot image first increases gradually, after
      reaching a maximum value, it decreases rapidly to a minimum value, meaning that
      there exists an optimum size of obscuration, which leads to the most intense hot
      image. Further analysis demonstrates that the optimum size of obscuration is
      approximately determined by the effective fastest growing spatial frequency for a
      given case. For the output light beam of a given intensity, with the gain
      coefficient of the Kerr medium slab increasing, or the loss coefficient
      decreasing, the optimum size of obscuration becomes bigger, while the hot image
      from the obscuration of a given size becomes weaker, suggesting that high gain
      and low loss can efficiently suppress the hot image from obscurations. The
      theoretical predictions are confirmed by numerical simulations.

PMID- 18327290
TI  - Evaluation and Control of Thiol-ene/Thiol-epoxy Hybrid Networks.
AB  - The development of thiol-ene/thiol-epoxy hybrid networks offers the advantage of
      tailorable polymerization kinetics while producing a highly crosslinked, high
      T(g) polymer that has significantly reduced shrinkage stress. Stoichiometric
      mixtures of pentaerythritol tetra(3-mercaptopropionate) (PETMP)/triallyl-1,3,5
      triazine-2,4,6-trione (TATATO) (thiol-ene, mixture 1) and PETMP/bisphenol a
      diglycidyl ether (BADGE) (thiol-epoxy, mixture 2) were prepared and hybrid
      mixtures of 75/25, 50/50, 25/75, and 10/90 w/w of mixtures 1 and 2 were
      polymerized using a combination of both radical and anionic initiation. The light
      exposure timing and the relative initiation conditions of the two types were used
      to control the order and relative rates of the radical and anionic
      polymerizations. The 50/50 w/w thiol-ene/thiol-epoxy hybrid material exhibited a
      final stress of only 0.2 MPa, which is 90 % lower than the stress developed in a
      control dimethacrylate resin. Kinetic analysis indicates composition affects
      network development in thiol-ene/thiol-epoxy hybrid networks and produces
      materials with robust mechanical properties.

PMID- 18327291
TI  - Continuous hemodiafiltration with PMMA Hemofilter in the treatment of patients
      with septic shock.
AB  - Septic shock is the most severe form of sepsis. It is widely accepted that
      cytokines play pivotal roles in the pathophysiology of septic shock. We reported
      previously that continuous hemodiafiltration (CHDF) using a
      polymethylmethacrylate (PMMA) membrane hemofilter removed various cytokines from
      blood continuously and efficiently, mainly by adsorption to membrane matrix of
      the hemofilter. Furthermore, in April 2000, we introduced to clinical practice a
      rapid assay system that determines blood levels of IL (interleukin)-6 in
      approximately 30 min. This enabled us to routinely measure blood IL-6 as an index
      of cytokine cascade activation in critically ill patients for real-time clinical
      monitoring of hypercytokinemia. The aim of the present cohort study was to
      evaluate the clinical efficacy of PMMA-CHDF in septic shock, a typical condition
      associated with hypercytokinemia. Forty-three patients with septic shock were
      assessed by monitoring of blood IL-6 level with a rapid assay system and
      immediate initiation of critical care including PMMA-CHDF for cytokine removal.
      Following initiation of PMMA-CHDF, early improvement of hemodynamics was noted,
      as well as an increase in urine output. PMMA-CHDF treatment improved both
      hypercytokinemia (assessed by measurement of blood IL-6 level) and dysoxia
      (assessed by measurement of blood lactate level). The present findings suggest
      that cytokine-oriented critical care using PMMA-CHDF might be an effective
      strategy for the treatment of septic shock.

PMID- 18327292
TI  - The giant anteater in the room: Brazil's neglected tropical diseases problem.

PMID- 18327294
TI  - Research--the profession's spine.

PMID- 18327293
TI  - Endogenous morphine in SH-SY5Y cells and the mouse cerebellum.
AB  - BACKGROUND: Morphine, the principal active agent in opium, is not restricted to
      plants, but is also present in different animal tissues and cell types, including
      the mammalian brain. In fact, its biosynthetic pathway has been elucidated in a
      human neural cell line. These data suggest a role for morphine in brain
      physiology (e.g., neurotransmission), but this hypothesis remains a matter of
      debate. Recently, using the adrenal neuroendocrine chromaffin cell model, we have
      shown the presence of morphine-6-glucuronide (M6G) in secretory granules and
      their secretion products, leading us to propose that these endogenous alkaloids
      might represent new neuroendocrine factors. Here, we investigate the potential
      function of endogenous alkaloids in the central nervous system. METHODOLOGY AND
      PRINCIPAL FINDINGS: Microscopy, molecular biology, electrophysiology, and
      proteomic tools were applied to human neuroblastoma SH-SY5Y cells (i) to
      characterize morphine and M6G, and (ii) to demonstrate the presence of the UDP
      glucuronyltransferase 2B7 enzyme, which is responsible for the formation of M6G
      from morphine. We show that morphine is secreted in response to nicotine
      stimulation via a Ca(2+)-dependent mechanism involving specific storage and
      release mechanisms. We also show that morphine and M6G at concentrations as low
      as 10(-10) M are able to evoke specific naloxone-reversible membrane currents,
      indicating possible autocrine/paracrine regulation in SH-SY5Y cells. Microscopy
      and proteomic approaches were employed to detect and quantify endogenous morphine
      in the mouse brain. Morphine is present in the hippocampus, cortex, olfactory
      bulb, and cerebellum at concentration ranging from 1.45 to 7.5 pmol/g. In the
      cerebellum, morphine immunoreactivity is localized to GABA basket cells and their
      termini, which form close contacts on Purkinje cell bodies.
      CONCLUSIONS/SIGNIFICANCE: The presence of morphine in the brain and its
      localization in particular areas lead us to conclude that it has a specific
      function in neuromodulation and/or neurotransmission. Furthermore, its presence
      in cerebellar basket cell termini suggests that morphine has signaling functions
      in Purkinje cells that remain to be discovered.

PMID- 18327295
TI  - A clinical practice guideline update from the CCA.CFCREAB-CPG.

PMID- 18327296
TI  - Ponder with me a few moments.

PMID- 18327298
TI  - Treatment of posttraumatic arthrofibrosis of the radioulnar joint with vibration
      therapy (VMTX Vibromax Therapeutics): a case report and narrative review of
      literature.
AB  - OBJECTIVE: To present the clinical features of post traumatic arthrofibrosis and
      response to treatment with Vibromax Therapeutics (VMTX) in 28 year old male
      soccer player. RATIONALE: Many studies have reported an increase in muscle
      performance after whole-body vibration, but to date none have evaluated the
      possibility of vibration application as a therapy for functional restoration
      after injury. CONCLUSIONS: Vibration training is being utilized in, strength
      training, performance enhancement and rehabilitation. Despite the lack of
      research in this area, the literature that is currently available and the results
      of this case study imply that vibration therapy has the potential to aid in the
      management of acute soft tissue injury and the sequela of disuse and
      immobilization.

PMID- 18327299
TI  - Determining spinal level using the inferior angle of the scapula as a reference
      landmark: a retrospective analysis of 50 radiographs.
AB  - OBJECTIVE: The purpose of this study was to determine which spinal segment most
      closely corresponds to the level of the inferior angle of the scapula (IAS) using
      measurements taken on A-P full-spine radiographs. METHODS: Fifty sequentially
      selected radiographs were analyzed independently by two examiners. A straight
      edge was used to ascertain which spinal levels corresponded with the right and
      left IASs. For analysis, each spinal level was subdivided into three regions:
      upper vertebral body, lower vertebral body, and intervertebral space. RESULTS: he
      mean spinal level corresponding to the left IAS was midway between the T8-9
      interspace and the upper T9 body (range, lower T7 to upper T10). The mean spinal
      level corresponding to the right IAS was slightly lower, but still within the
      upper T9 body (range, lower T7 to lower T10). These levels correspond to the T8
      spinous process. CONCLUSIONS: There is a considerable amount of variability in
      where the IASs are located, but most commonly, they correspond to the level of
      the upper body of T9.

PMID- 18327300
TI  - Ultrasound in the management of osteoarthritis: part I: a review of the current
      literature.
AB  - BACKGROUND: Ultrasound has been widely used in clinical settings for the
      management of various ailments but many authors still question its efficacy. An
      accumulating body of literature demonstrates that ultrasound evokes a broad
      spectrum of bioeffects which may be therapeutically beneficial in the management
      of a variety of clinical conditions. OBJECTIVE: A critical review the current
      research investigating the use of therapeutic ultrasound in the treatment and/or
      management of osteoarthritis. Specific emphasis is placed on interpreting the
      literature in the context of its strengths and weaknesses, with particular
      attention placed on study protocols and technical parameters used in the trials.
      Relevant basic science is also introduced and meaningful inter-study comparisons
      are highlighted with suggestions for future research. DESIGN: Literature Review.
      METHODS: A Pubmed search of the literature was performed from 1985 to present
      using the key words "ultrasound" and "osteoarthritis" retrieved a total of 313
      publications. Experimental, clinical and animal studies that directly assessed
      applications of therapeutic ultrasound in the clinical management of
      osteoarthritis and/or its underlying physiologic mechanisms were accepted.
      Studies that evaluated ultrasound in combination with other modalities were
      accepted but their conclusions were interpreted in the context of their
      methodological strengths and limitations. RESULTS: A total of 17 articles met our
      search criteria; one study was excluded due to poor methodology. Of a total of
      five review papers, two concluded that ultrasound had positive therapeutic
      effects, two did not demonstrate any benefit and one was inconclusive. The
      remaining nine studies consistently reported that ultrasound has therapeutically
      beneficial effects on pain and functional outcomes. Five studies reported that
      ultrasound has positive cartilage healing properties and one experimental study
      demonstrated increased intra-articular absorption of high molecular weight
      molecules (hyaluronan) using ultrasound phonophoresis. Only one randomized
      controlled trial reported no effect on pain or active range of motion when
      ultrasound is used in combination with exercise. CONCLUSIONS: Ultrasound
      demonstrates the ability to evoke a broad range of therapeutically beneficial
      effects which may provide safe and effective applications in the management of
      osteoarthritis.

PMID- 18327301
TI  - William D. Harper, Jr, MS, DC: anything can cause anything.
AB  - Trained as an engineer and a chiropractor, William D. Harper, Jr. made his career
      in the healing arts as instructor, writer and president of the Texas Chiropractic
      College (TCC). A native of Texas who grew up in various locales in the Lone Star
      State, in Mexico and in the Boston area, he took his bachelor's and master's
      degree in engineering in 1933 and 1934 from the Massachusetts Institute of
      Technology, and his chiropractic degree at TCC in 1942. Dissatisfied with the
      "foot-on-the-hose" concept of subluxation syndrome (D.D. Palmer's second theory),
      Dr. Harper studied and wrote about aberrant neural irritation as an alternative
      explanation for disease and for the broad clinical value he perceived in the
      chiropractic art. In this he paralleled much of D.D. Palmer's third theory of
      chiropractic. His often reprinted textbook, Anything Can Cause Anything, brought
      together much of what he had lectured and written about in numerous published
      articles. He was well prepared for the defense of chiropractic that he offered in
      1965 in the trial of the England case in federal district court in Louisiana. The
      case was lost when the court ruled that the legislature rather than the judiciary
      should decide whether to permit chiropractors to practice, but Harper's
      performance was considered excellent. He went on to guide the TCC as president
      from 1965 through 1976, its first 11 years after relocating from San Antonio to
      Pasadena, Texas. Harper built the school - its faculty, staff and facilities -
      from very meager beginnings to a small but financially viable institution when he
      departed. Along the way he found fault with both chiropractic political camps
      that vied for federal recognition as the accrediting agency for chiropractic
      colleges in the United States. Dr. Bill Harper was a maverick determined to do
      things his way, and in many respects he was successful. He left a mark on the
      profession that merits critical analysis.

PMID- 18327302
TI  - Re: JCCA 2007; 51(2):91-9. Page S. An audit of health products and services
      marketed on chiropractic websites in Alberta and consideration of these practices
      in the context of chiropractic codes of conduct and ethics.

PMID- 18327303
TI  - Pioglitazone, a PPAR-gamma ligand, exerts cytostatic/cytotoxic effects against
      cancer cells, that do not result from inhibition of proteasome.
AB  - Thiazolidinediones are oral antidiabetic agents that activate peroxisome
      proliferator-activated receptor-gamma (PPAR-gamma) and exert potent antioxidant
      and anti-inflammatory properties. It has also been shown that PPAR-gamma agonists
      induce G0/G1 arrest and apoptosis of malignant cells. Some of these effects have
      been suggested to result from inhibition of proteasome activity in target cells.
      The aim of our studies was to critically evaluate the cytostatic/cytotoxic
      effects of one of thiazolidinediones (pioglitazone) and its influence on
      proteasome activity. Pioglitazone exerted dose-dependent cytostatic/cytotoxic
      effects in MIA PaCa-2 cells. Incubation of tumor cells with pioglitazone resulted
      in increased levels of p53 and p27 and decreased levels of cyclin D1.
      Accumulation of polyubiquitinated proteins within cells incubated with
      pioglitazone suggested dysfunction of proteasome activity. However, we did not
      observe any influence of pioglitazone on the activity of isolated proteasome and
      on the proteolytic activity in lysates of pioglitazone-treated MIA PaCa-2 cells.
      Further, treatment with pioglitazone did not cause an accumulation of fluorescent
      proteasome substrates in transfected HeLa cells expressing unstable GFP variants.
      Our results indicate that pioglitazone does not act as a direct or indirect
      proteasome inhibitor.

PMID- 18327304
TI  - 70 years of Landau-Teller theory for collisional energy transfer. Semiclassical
      three-dimensional generalizations of the classical collinear model.
AB  - This article, in historical retrospective, describes the development of the
      celebrated Landau-Teller (LT) model of 1936 for vibrational-translational energy
      exchange in collisions of an atom with a diatomic molecule. We discuss
      semiclassical generalizations of the classical LT model and generalizations of
      the collinear LT model to account for the effects of rotation of the diatom on
      the vibrational relaxation rate. The former is based on the recovery of the
      Landau semiclassical exponent from the classical LT encounter time, and the
      latter on the definition of a 1-D driving mode within the manifold of the
      translational and rotational degrees of freedom of the colliding partners. The
      utility of generalized LT models is illustrated by three case studies that
      exemplify weak and strong effects of the rotation as well as the efficiencies of
      different driving modes in the vibrational relaxation of highly asymmetric
      diatoms.

PMID- 18327305
TI  - Vibrational spectra of small silicon monoxide cluster cations measured by
      infrared multiple photon dissociation spectroscopy.
AB  - The first gas-phase infrared spectra of silicon monoxide cations (SiO)(n)(+), n =
      3-5, using multiple photon dissociation in the 550-1250 cm(-1) frequency range,
      are reported. All clusters studied here fragment via loss of a neutral SiO unit.
      The experimental spectra are compared to simulated linear absorption spectra from
      calculated low energy isomers for each cluster. This analysis indicates that a
      "ring" isomer is the primary contributor to the (SiO)(3)(+) spectrum, that the
      (SiO)(4)(+) spectrum results from two close-lying bicyclic ring isomers, and that
      the (SiO)(5)(+) spectrum is from a bicyclic ring with a central, fourfold
      coordinated Si atom. Experiment and theory indicate that the energies and
      energetic orderings of (SiO)(n)(+) isomers differ from those for neutral (SiO)(n)
      clusters.

PMID- 18327306
TI  - Cleavage of the ether bond by electron impact: differences between linear ethers
      and tetrahydrofuran.
AB  - Dissociative electron attachment (DEA) to diethyl ether yielded primarily the
      C(2)H(5)O(-) ion, with a strong Feshbach resonance band at 9.1 eV and a weaker
      shape resonance band at 3.89 eV. Very similar spectra were obtained for dibutyl
      ether, with C(4)H(9)O(-) bands at 8.0 and 3.6 eV. Some of these primary ions
      subsequently lost H(2) and yielded weaker signals of the C(2)H(3)O(-) and
      C(4)H(7)O(-) ions. In contrast, DEA to the cyclic ether tetrahydrofuran (THF)
      yielded mainly a fragment of mass 41, presumably deprotonated ketene, at 7.65 eV.
      The low-energy band was missing in THF. H(-) with two bands at 6.88 and 8.61 eV,
      and an ion of mass 43 (presumably deprotonated acetaldehyde) with two bands at
      6.7 and 8.50 eV were also observed. We propose that in the primary DEA step the C
      O bond is cleaved in both the open-chain and the cyclic ethers. In the open-chain
      ethers the excess energy is partitioned between the (internal and kinetic)
      energies of two fragments, resulting in an RO(-) ion cool enough to be observed.
      The CH(2)(CH(2))(3)O(-) ion resulting from cleavage of the C-O bond in THF
      contains the entire excess energy (more than 6 eV at an electron energy of 7.65
      eV) and is too short-lived with respect to further dissociation and thermal
      autodetachment to be detected in a mass spectrometer. These findings imply that
      there could be a substantial difference between the fragmentation in the gas
      phase described here and fragmentation in the condensed phase where the initially
      formed fragments can be rapidly cooled by the environment.

PMID- 18327307
TI  - Reactive landing of peptide ions on self-assembled monolayer surfaces: an
      alternative approach for covalent immobilization of peptides on surfaces.
AB  - Soft landing of mass-selected peptide ions onto reactive self-assembled monolayer
      surfaces (SAMs) was performed using a newly constructed ion deposition apparatus.
      SAM surfaces before and after soft landing were characterized ex situ using time
      of-flight secondary-ion mass spectrometry (TOF-SIMS) and infrared reflection
      absorption spectroscopy (IRRAS). We demonstrate that reactive landing (RL)
      results in efficient covalent linking of lysine-containing peptides onto the SAM
      of N-hydroxysuccinimidyl ester-terminated alkylthiol on gold (NHS-SAM).
      Systematic studies of the factors that affect the efficiency of RL revealed that
      the reaction takes place upon collision and is promoted by the kinetic energy of
      the ion. The efficiency of RL is maximized at ca. 40 eV collision energy. At high
      collision energies the RL efficiency decreases because of the competition with
      scattering of ions off the surface. The reaction yield is independent of the
      charge state of the projectile ions, suggesting that peptide ions undergo
      efficient neutralization upon collision. Chemical and physical properties of the
      SAM surface are also important factors that affect the outcome of RL. The
      presence of chemically reactive functional groups on the SAM surface
      significantly improves the reaction efficiency. RL of mass- and energy-selected
      peptide ions on surfaces provides a highly specific approach for covalent
      immobilization of biological molecules onto SAM surfaces.

PMID- 18327308
TI  - Electron capture by pentafluoronitrobenzene and pentafluorobenzonitrile.
AB  - Electron attachment to pentafluorobenzonitrile (C(6)F(5)CN) and
      pentafluoronitrobenzene (C(6)F(5)NO(2)) is studied in the energy range 0-16 eV by
      means of a crossed electron-molecular beam experiment with mass spectrometric
      detection of the anions. We find that pentafluoronitrobenzene exclusively
      generates fragment anions via dissociative electron attachment (DEA), while
      pentafluorobenzonitrile forms a long lived parent anion within a narrow energy
      range close to 0 eV and additionally undergoes DEA at higher energies. This is in
      contrast to the behaviour of the non-fluorinated analogues as in nitrobenzene the
      non-decomposed anion is formed while in benzonitrile only DEA is observed. The
      associated reactions involve simple bond cleavages but also complex unimolecular
      decompositions associated with structural and electronic rearrangement also
      resulting in the deterioration of the cyclic structure.

PMID- 18327309
TI  - Structure and stability of HSNO, the simplest S-nitrosothiol.
AB  - High-level ab initio calculations employing the CCSD and CCSD(T) coupled cluster
      methods with a series of systematically convergent correlation-consistent basis
      sets have been performed to obtain accurate molecular geometry and energetic
      properties of the simplest S-nitrosothiol (RSNO), HSNO. The properties of the S-N
      bond, which are central to the physiological role of RSNOs in the storage and
      transport of nitric oxide, are highlighted. Following corrections for quadruple
      excitations, core-valence correlation and relativistic effects, the CCSD(T)
      method extrapolated to the complete basis set (CBS) limit yielded values of 1.85
      A and 29.2 kcal mol(-1) for the S-N bond length and the dissociation energy for
      homolysis of the S-N bond, respectively, in the energetically most stable trans
      conformer of HSNO. The properties of the S-N bond strongly depend on the basis
      set size and the inclusion of triple, and, to a lesser extent, quadruple
      excitations in the coupled cluster expansion. CCSD calculations systematically
      underestimate the S-N equilibrium distance and S-N bond dissociation energy by
      0.05-0.07 A and 6-7 kcal mol(-1), respectively. The significant differences
      between the CCSD(T) and CCSD descriptions of HSNO, the high values of the coupled
      cluster T(1) (0.027) and D(1) (0.076) diagnostics, as well as the instability of
      the reference restricted Hartree-Fock (RHF) wavefunction indicate that the
      electronic structure of the SNO group possesses multireference character.
      Previous quantum-chemical data on RSNOs are reexamined based on the new insight
      into the SNO electronic structure obtained from the present high-level
      calculations on HSNO.

PMID- 18327310
TI  - LIF studies of iodine oxide chemistry. Part 3. Reactions IO + NO3 --> OIO + NO2,
      I + NO3 --> IO + NO2, and CH2I + O2 --> (products): implications for the
      chemistry of the marine atmosphere at night.
AB  - The technique of pulsed laser photolysis coupled to LIF detection of IO was used
      to study IO + NO(3) --> OIO + NO(2); I + NO(3) --> (products); CH(2)I + O(2) -->
      (products); and O((3)P) + CH(2)I(2) --> IO + CH(2)I, at ambient temperature. was
      observed for the first time in the laboratory and a rate coefficient of k(1 a) =
      (9 +/- 4) x 10(-12) cm(3) molecule(-1) s(-1) obtained. For , a value of k(2) (298
      K) = (1.0 +/- 0.3) x 10(-10) cm(3) molecule(-1) s(-1) was obtained, and a IO
      product yield close to unity determined. IO was also formed in a close-to-unity
      yield in , whereas in an upper limit of alpha(3)(IO) < 0.12 was derived. The
      implications of these results for the nighttime chemistry of the atmosphere were
      discussed. Box model calculations showed that efficient OIO formation in was
      necessary to explain field observations of large OIO/IO ratios.

PMID- 18327311
TI  - Co-adsorption of CO onto a Ag-modified Pt(111)--restructuring of a Ag UPD layer
      monitored by EC-STM.
AB  - The effect of co-adsorption of CO on an underpotentially deposited (UPD) silver
      monolayer on a Pt(111) single crystal electrode in 0.05 M sulfuric acid is
      investigated for the first time by means of electrochemical scanning tunneling
      microscopy (EC-STM). Pure electrochemical experiments suggest that the co
      adsorption of CO onto Pt single crystal electrodes previously modified by a
      monolayer of Ag, forces Ag atoms of the first UPD monolayer into a second
      adlayer. The present EC-STM studies reveal the formation of a large-area Ag
      network after the co-adsorption of CO. The resulting Ag nanostructures formed on
      wide Pt(111) terraces are approximately 0.5 nm high and 10 nm wide. The
      desorption of the newly formed second Ag adlayer, the oxidation of CO and the
      desorption of Ag atoms from the first adlayer are monitored by EC-STM and
      simultaneously detected in the corresponding CVs in three different oxidation
      peaks. EC-STM images recorded afterwards show the unchanged Pt surface. The
      presence of Ag on the surface leads to a downward shift of the onset of oxygen
      adsorption on the Pt(111) surface.

PMID- 18327312
TI  - Study of the factors affecting the photoelectrode characteristics of a
      perylene/phthalocyanine bilayer working in the water phase.
AB  - Some types of phthalocyanines (MPc (M = H(2), Cu, or Zn), a p-type semiconductor)
      were used in combination with 3,4,9,10-perylenetetracarboxyl-bisbenzimidazole
      (PTCBI, an n-type semiconductor), with which those photoelectrode characteristics
      in the water phase were investigated in terms of kinetics. Each film of the
      PTCBI/MPc bilayer functioned as a photoanode, where the photoinduced oxidation of
      thiol occurs at the MPc/water interface along with the hole conduction through
      the MPc layer. The holes originate on account of the photophysical events in the
      p/n interior, involving the charge separation of excitons at the p/n interface.
      The typical photoelectrochemical characteristic in the PTCBI/MPc photoanodes
      involved a transient photocurrent occurring in the initial stage under
      illumination (under potentiostatic conditions): thereafter, it attained a steady
      state. Moreover, both the initial spiky photocurrents and the steady-state
      photocurrents exhibited saturation at higher concentrations. An analysis with
      photoelectrode kinetics was performed by assuming an adsorption step prior to a
      rate-limiting charge transfer step, where equations were applied to photocurrents
      based on the Langmuir adsorption equilibrium. The kinetic analyses evidently
      showed that the photoanodic reactions are kinetically dominated by the charge
      transfer between MPc and thiol, where the overall kinetics for thiol oxidation
      decreases in the following order: H(2)Pc > ZnPc > CuPc; that is, it appeared that
      H(2)Pc acts as the more efficient photofunctional interface capable of oxidation
      in the water phase when PTCBI was concurrently employed as an electron conductor.
      Considering that the photocurrent generated is proportional to the surface
      concentration of thiol (Gamma) at the MPc as well as the intrinsic oxidation rate
      (cf., ZnPc > H(2)Pc approximately CuPc), the higher efficiency in the output at
      the H(2)Pc surface was attributed to an exceptionally high Gamma (i.e., from the
      kinetic analyses, the Gamma value at the H(2)Pc surface was also inferred to be 2
      3 times higher than that at the other MPcs). Through the present kinetic
      analysis, it also revealed that the activity for thiol oxidation taking place at
      Pc ring is comparable to that at the conventional active catalysts (i.e.,
      polycarboxyphthalocyaninato Co(ii) and Fe(iii)) where a central metal is an
      active site.

PMID- 18327313
TI  - Dis-aggregation of an insoluble porphyrin in a calixarene matrix:
      characterization of aggregate modes by extended dipole model.
AB  - In this paper, the different aggregation modes of a water-insoluble porphyrin
      (EHO) mixed with an amphiphilic calix[8]arene (C8A), at the air-water interface
      and in Langmuir-Blodgett (LB) film form, are analyzed as a function of the mixed
      composition. The strategy used to control the EHO aggregation has consisted of
      preparing mixed thin films containing EHO and C8A, in different ratios, at the
      air-water interface. Therefore, the increase of the C8A molar ratio in the mixed
      film diminishes the aggregation of the EHO molecules, although such an effect
      must be exclusively related to the dilution of the porphyrin. The reflection
      spectra of the mixed C8A-EHO films registered at the air-water interface, show a
      complex Soret band exhibiting splitting, hypochromicity and broadening features.
      Also, during the transfer process at high surface pressure, it has been shown
      that the EHO molecules are ejected from the C8A monolayer and only a fraction of
      porphyrin is transferred to the solid support, in spite of a complete transfer
      for the C8A matrix. The complex structure of the reflection spectra at the air
      water interface, as well as the polarization dependence of the absorption spectra
      for the mixed LB films, indicate the existence of four different arrangements for
      the EHO hosted in the C8A matrix. The aggregate formation is governed by two
      factors: the attraction between the porphyrin rings which minimizes their
      separation, and the alkyl chain interactions, that is, hydrophobic effect and/or
      steric hindrance which determine and restrict the possible aggregation
      structures. By using the extended dipole model, the assignment of the spectral
      peaks observed to different EHO aggregates is shown.

PMID- 18327314
TI  - Probing proton dissociation in ionic polymers by means of in situ ATR-FTIR
      spectroscopy.
AB  - The hydration process of cationic membrane protogenic groups was investigated
      using in situ ATR-FTIR spectroscopy. The aim of this study is to provide a
      relationship between the hydration degree of the membrane and the dissociation
      state of exchange sites inside the polymer material. IR spectra were recorded by
      means of an environmental device specifically manufactured to allow the control
      of water vapour pressure in equilibrium with the sample. The behaviour of Nafion
      112 and sulfonated poly(ether ether ketone) (S-PEEK), in both proton and sodium
      forms, was compared. IR data, analyzed and fitted in the 800-1850 cm(-1) spectral
      range, gave precise information on the assignment of sulfonic group vibrational
      modes. The results of this study improve the understanding of the transition
      phenomena between dissociated and undissociated states of the grafted sites in
      protonic conductors.

PMID- 18327315
TI  - Liquid phase calorimetry and adsorption analyses of zeolite beta acidity.
AB  - Zeolite beta acidity, activated at 550 degrees C, was characterized by
      calorimetric and adsorption studies of pyridine in cyclohexane (Cal-Ad). Two
      different acid sites were found: n(1) = 0.1612 mmol g(-1) with DeltaH(1) = -83.6
      kJ mol(-1); and n(2) = 0.3820 mmol g(-1) with DeltaH(2) = -62.8 kJ mol(-1). Step
      calcinations followed by FTIR indicated n(1) as Lewis sites and n(2) as weak
      Bronsted sites. When activated at 450 degrees C, zeolite beta showed three
      different sites: n(1) = 0.0467 mmol g(-1) with DeltaH(1) = -227.3 kJ mol(-1);
      n(2) = 0.1163 mmol g(-1) with DeltaH(2) = -93.3 kJ mol(-1); and n(3) = 0.3322
      mmol g(-1) with DeltaH(3) = -80.4 kJ mol(-1). Sites n(1) and n(2) were assigned
      as Bronsted centers, while n(3) as a combination of Bronsted and Lewis sites.
      These results suggest that the zeolite beta strongest Bronsted sites are
      converted to Lewis sites at 550 degrees C. These Lewis sites are not only related
      to extra-framework Al species, but also to aluminium atoms partially bonded to
      the zeolite framework, as evidenced by infrared bands at 3777 and 875 cm(-1).
      FTIR and thermogravimetric analyses of gas phase adsorbed pyridine were also used
      to investigate the materials acidity and a good agreement was found with Cal-Ad
      data. The results showed that the Cal-Ad method offers a more detailed
      description of the zeolite surface acidity by providing thermodynamic parameters
      not easily obtained by other techniques. A linear relationship between enthalpy
      and entropy values for several zeolites (ZSM-5, TS-1, MOR, Y and BEA) is also
      reported.

PMID- 18327316
TI  - Is vanadium a more versatile target in the activity of primordial life forms than
      hitherto anticipated?
AB  - The two predominant forms of vanadium occurring in the geo-, aqua- and biosphere,
      soluble vanadate(V) and insoluble oxovanadium(IV) (vanadyl), are subject to
      bacterial activity and transformation. Bacteria belonging to genera such as
      Shewanella, Pseudomonas and Geobacter can use vanadate as a primary electron
      acceptor in dissimilation or respiration, an important issue in the context of
      biomineralisation and soil detoxification. Azotobacter, which can employ vanadium
      as an essential element in nitrogen fixation, secretes a vanadophore which
      enables the uptake of vanadium(V). Siderophores secreted by other bacteria
      competitively (to ferric iron) take up vanadyl and thus interfere with iron
      supply, resulting in bacteriostasis. The halo-alkaliphilic Thioalkalivibrio
      nitratireducens possibly uses vanadium as a constituent of an alternative,
      molybdopterin-free nitrate reductase. Marine macro-algae can generate a variety
      of halogenated organic compounds by use of vanadate-dependent haloperoxidases,
      and a molecular vanadium compound, amavadin, from Amanita mushrooms has turned
      out to be an efficient catalyst in oxidation reactions. The present account is a
      focused and critical review of the current knowledge of the interplay of bacteria
      and other primitive forms of life (cyanobacteria, algae, fungi and lichens) with
      vanadium, with the aim to provide perspectives for applications and further
      investigations.

PMID- 18327317
TI  - Thiol cofactors for selenoenzymes and their synthetic mimics.
AB  - The importance of selenium as an essential trace element is now well recognized.
      In proteins, the redox-active selenium moiety is incorporated as selenocysteine
      (Sec), the 21st amino acid. In mammals, selenium exerts its redox activities
      through several selenocysteine-containing enzymes, which include glutathione
      peroxidase (GPx), iodothyronine deiodinase (ID), and thioredoxin reductase
      (TrxR). Although these enzymes have Sec in their active sites, they catalyze
      completely different reactions and their substrate specificity and cofactor or co
      substrate systems are significantly different. The antioxidant enzyme GPx uses
      the tripeptide glutathione (GSH) for the catalytic reduction of hydrogen peroxide
      and organic peroxides, whereas the larger and more advanced mammalian TrxRs have
      cysteine moieties in different subunits and prefer to utilize these internal
      cysteines as thiol cofactors for their catalytic activity. On the other hand, the
      nature of in vivo cofactor for the deiodinating enzyme ID is not known, although
      the use of thiols as reducing agents has been well-documented. Recent studies
      suggest that molecular recognition and effective binding of the thiol cofactors
      at the active site of the selenoenzymes and their mimics play crucial roles in
      the catalytic activity. The aim of this perspective is to present an overview of
      the thiol cofactor systems used by different selenoenzymes and their mimics.

PMID- 18327318
TI  - Auxotrophic-precursor directed biosynthesis of nonribosomal lipopeptides with
      modified tryptophan residues.
AB  - Feeding 5-hydroxy and 5-fluorotryptophan to a Streptomyces coelicolor Trp
      auxotrophic strain WH101 results in the production of a number of new calcium
      dependent antibiotics (CDAs) possessing modified Trp residues. It is anticipated
      that this method could be used to modulate the biological properties of Trp
      containing nonribosomal peptide natural products, or to generate analogues with
      useful fluorescent properties for studying biological mechanisms of action.

PMID- 18327319
TI  - de novo design and synthesis of N-benzylanilines as new candidates for VEGFR
      tyrosine kinase inhibitors.
AB  - N-Benzylanilines were designed and synthesized as vascular endothelial growth
      factor (VEGF)-2 inhibitors using de novo drug design systems based on the X-ray
      structure of VEGFR-2 kinase domain. Among compounds synthesized, compound showed
      the most potent inhibitory activity toward VEGFR-2 (KDR) tyrosine kinase and its
      IC(50) value was 0.57 microM.

PMID- 18327320
TI  - Metastable tert-butylcalix[6]arene with unusually large tunable free volume for
      non-threshold enclathration of volatiles.
AB  - A metastable material with tunable free volume of molecular size, vapor sorption
      properties of a porous sorbent and variable thermal stability was prepared from
      tert-butylcalix[6]arene.

PMID- 18327321
TI  - A novel efficient and versatile route to the synthesis of 5-O-feruloylquinic
      acids.
AB  - A novel synthesis of 5-O-feruloylquinic acid, a polyphenolic compound found in
      coffee beans, and its methyl ester derivative has been optimized. The sequence
      involves 6 steps and is compatible with the preparation of potential human
      metabolites of these compounds. The key reaction is a Knoevenagel condensation of
      4-hydroxy-3-methoxy-benzaldehyde and a malonate ester of quinic acid.

PMID- 18327322
TI  - Facile one-pot synthesis of 5-substituted hydantoins.
AB  - 5-Substituted and 5,5-disubstituted hydantoins are synthesised from the
      corresponding aldehydes or ketones, using a one-pot, gallium(III) triflate
      catalysed procedure that is compatible with a range of substrates and solvents.

PMID- 18327323
TI  - Efficient palladium-catalyzed synthesis of 3-aryl-4-indolylmaleimides.
AB  - Improved palladium catalysts for the Suzuki coupling of 3-bromo-1-methyl-4-(2
      methyl-3-indolyl)maleimide have been developed. The coupling of both aryl- and
      heteroarylboronic acids proceeds smoothly in good to excellent yields at low
      catalyst loading.

PMID- 18327324
TI  - Guest exchange in dimeric capsules formed by tetra-urea calix[4]arenes.
AB  - Ten tetra-urea calix[4]arene derivatives with different ether residues (methyl,
      pentyl, benzyl, all combinations of methyl and pentyl, 1,3-dibenzyl-2,4
      dipentyl), including also the tetrahydroxy compound and the 1,3-dipentyl ether,
      were synthesised. Their urea groups were substituted with a lipophilic residue to
      ensure sufficient solubility in cyclohexane. Thus, kinetics for the exchange of
      the included guest (benzene) against the solvent (cyclohexane) could be followed
      by 1H NMR spectroscopy. The apparent first order rate constants decrease with
      increasing size of the ether residues from methyl to benzyl by more than three
      orders of magnitude. This can be understood by a decreasing flexibility/mobility
      of the calixarene skeleton. In line with this explanation is the rather slow
      exchange for the tetrahydroxy compound, where the cone conformation is stabilised
      by a cyclic array of intramolecular OH...OH hydrogen bonds.

PMID- 18327325
TI  - Cyclic triureas--synthesis, crystal structures and properties.
AB  - The synthesis of 24-membered macrocycles is described, in which rigid xanthene
      units (X) and/or diphenyl ether units (D) as flexible analogues are linked via
      urea groups. All four possible combinations (XXX, XXD, XDD, DDD) have been
      obtained with yields of 40-72% for the cyclisation step. In two cases, the
      respective cyclic hexamers (XXDXXD, XXXXXX) were also isolated. Two compounds
      have been characterised by a single crystal X-ray analysis of the free triurea
      (XXD, XDD) and one example (DDD) by its complex with tetrabutylammonium chloride.
      It shows the chloride anion in the centre of the macrocycle, held by six NH...Cl-
      hydrogen bonds. The interaction with various other anions has been studied by 1H
      NMR. Complexation constants for chloride, bromide and acetate have been measured
      for all trimers by UV spectrophotometry. Molecular dynamics simulations have been
      carried out to determine the conformation of the free receptors in chloroform and
      acetonitrile. They show that in chloroform, intramolecular hydrogen bonding
      occasionally facilitated by trans-->cis isomerisation of an amide bond dominates
      the conformation of the macrocycles while in acetonitrile (the solvent used for
      complexation measurements), the ligating urea NH protons are properly arranged
      for the complexation of anions, however, their strong solvation is counteractive
      to the complexation.

PMID- 18327326
TI  - Solubilisation of [60]fullerenes using block copolymers and evaluation of their
      photodynamic activities.
AB  - Unmodified [60]fullerenes (C60) were solubilised with high stability using
      various type of poly(ethylene glycol) (PEG) based block copolymer micelles. Block
      copolymer micelle-incorporated C60 fullerenes were studied in cultures for
      biological activities using human cervical cancer HeLa cells. As a result, the
      cationic block copolymer micelles delivered C60 into the cells depending on their
      surface densities and showed cytotoxicity under photoirradiation.

PMID- 18327327
TI  - A ratiometric optical imaging probe for intracellular pH based on modulation of
      europium emission.
AB  - A set of three pH-responsive ratiometric Eu(III)complexes has been synthesised
      incorporating a coordinated azathioxanthone sensitiser and a pH dependent
      alkylsulfonamide moiety. Emission properties, anion binding affinities, pH
      response curves and protein binding constants were studied in detail in aqueous
      media, and solutions containing various concentrations of interfering anions and
      protein were also examined. The complex, [EuL3] exhibited some interference from
      protein and endogenous anions, e.g. lactate and hydrogen carbonate, but possessed
      a protonation constant of 7.2 in human serum solution. A suitable calibration
      curve was obtained and was used to determine the local pH using a 680/589 nm
      intensity ratio vs. pH plot. Confocal fluorescence microscopy images revealed
      fast uptake of the complex and a well distributed localisation within the cell;
      fast egress also occurred. Ribosomal localisation, with a high concentration
      within the protein-dense nucleoli was observed, in a similar manner to
      structurally related complexes bearing the same coordinated sensitising moiety.
      An IC(50) value of 67 (+/-20) microM was estimated using an MTT assay. Selected
      emission band ratio versus pH plots allow pH measurement in the range 6 to 8,
      enabling intracellular pH to be measured by microscopy. A value of 7.4 was
      estimated for NIH 3T3 cells in the protein rich regions of the nucleolus and
      ribosomes.

PMID- 18327328
TI  - Simple and facile synthesis of tetralone-spiro-glutarimides and spiro
      bisglutarimides from Baylis-Hillman acetates.
AB  - A simple and convenient synthesis of di(E)-arylidene-tetralone-spiro-glutarimides
      from Baylis-Hillman acetates via an interesting biscyclization strategy involving
      facile C-C and C-N bond formation is described. Also, one-pot multistep
      transformation of the Baylis-Hillman acetates into di(E)-arylidene-spiro
      bisglutarimides is presented.

PMID- 18327329
TI  - Palladium-catalyzed synthesis of indene derivatives via propargylic carbonates
      with in situ generated organozinc compounds.
AB  - The palladium-catalyzed carboannulation and arylation reaction of propargylic
      carbonates with in situ generated organozinc compounds produced an important new
      class of indene derivatives. The reaction proceeded under mild conditions, and
      indene products were isolated in good to excellent yields.

PMID- 18327330
TI  - Photochemistry of 5-allyloxy-tetrazoles: steady-state and laser flash photolysis
      study.
AB  - The photochemistry of three 5-allyloxy-tetrazoles, in methanol, acetonitrile and
      cyclohexane was studied by product analysis and laser flash photolysis. The
      exclusive primary photochemical process identified was molecular nitrogen
      elimination, with formation of 1,3-oxazines. These compounds were isolated in
      reasonable yields by column chromatography on silica gel and were fully
      characterized. DFT(B3LYP)/6-31G(d,p) calculations predict that these 1,3-oxazines
      can adopt two tautomeric forms (i) with the NH group acting as a bridge
      connecting the oxazine and phenyl rings and (ii) with the -N=bridge and the
      proton shifted to the oxazine ring. Both tautomeric forms are relevant in the
      photolysis of oxazines in solution. Secondary reactions were observed, leading to
      the production of phenyl vinyl-hydrazines, enamines, aniline and phenyl
      isocyanate. Transient absorption, detected by laser flash photolysis, is
      attributed to the formation of triplet 1,3-biradicals generated from the excited
      5-allyloxy-tetrazoles. The 1,3-biradicals are converted to 1,6-biradicals by
      proton transfer, which, after intersystem crossing, decay to generate the
      products. Solvent effects on the photoproduct distribution and rate of
      decomposition are negligible.

PMID- 18327331
TI  - Preparation and purification of 5'-amino-5'-deoxyguanosine-5'-N-phosphoramidate
      and its initiation properties with T7 RNA polymerase.
AB  - 5'-Amino-5'-deoxyguanosine-5'-N-phosphoramidate (GNHP) was synthesised in four
      steps from guanosine. Its identity was confirmed using spectroscopic and kinetic
      studies. A chromatographic method for the purification of this unstable compound
      was developed. GNHP was found to initiate T7 RNAP promoted transcriptions to
      afford 5'-O3P-NH-RNA, which hydrolyses readily to yield 5'-H2N-RNA that can be
      conjugated to activated esters.

PMID- 18327332
TI  - Efficient cleavage of the N-O bond of 3,6-dihydro-1,2-oxazines mediated by some
      alpha-hetero substituted carbonyl compounds in mild conditions.
AB  - The efficient cleavage of the N-O bond of some nitroso Diels-Alder cycloadducts
      has been achieved in mild conditions, mediated either by 2,2-dimethyl-1,3-dioxan
      5-one or 1,3-dithiolane-2-carboxaldehyde. These new and purely organic conditions
      allow an excellent tolerance with respect to many functional groups that would
      have been affected by previous reductive cleavage conditions.

PMID- 18327333
TI  - Enols and thioenols of substituted cyanomonothiocarbonylmalonamides: structures,
      enolization vs. thioenolization, equilibria and conformations.
AB  - Condensation of organic isothiocyanates with cyanoacetamides gave 24 N- and N'
      substituted cyanomonothiocarbonylmalonamides in different tautomeric ratios i.e.,
      amide-thioamides (TMA)R3NHCSCH(CN)CONR1R2 (12), thioamide-enols of amides (E)
      R3NHCSC(CN)=C(OH)NR1R2 (11)or amide-thioenols (TE) R3NHC(SH)=C(CN)CONR1R2 (13).
      The equilibrium constants (K(thioenol) =[TE]/[TMA] and K(enol) = [E]/[TMA]) in
      solution depend on R1, R2, R3 and the solvent. The %(E + TE)for NR1R2 increases
      in the order NMe2 < NHMe < NH2. The (K(thioenol) + K(enol)) in various solvents
      follows the order CCl4 > CDCl3 > C6D6 > THF-d8 > (CD3)2CO > CD3CN > DMF-d7 > DMSO
      d6. The delta(OH) values are 16.46-17.43 and the delta(SH) values are 3.87-5.26
      ppm in non polar solvents, e.g.,CDCl3 and 6.34-6.97 ppm in THF-d8 and CD3CN. An
      intramolecular O-H...O hydrogen bond leads to the preferred Z-configuration of
      the enols, and an N-H...O bond stabilizes the thioenols' preferred E
      configuration with a non-bonded SH in solution. X-Ray crystallography revealed
      that systems with high %(E + TE) in solution mostly display the enols 11 in the
      solid state and systems with lower %(E +TE) in solution display structure 12. The
      differences in delta(OH), delta(NH), K(enol) and crystallographic data for
      analogous enol and thioenol systems are compared.

PMID- 18327334
TI  - Solar one-way photoisomerisation of 5',8-cyclo-2'-deoxyadenosine.
AB  - Under sunlight irradiation (5'S)-5',8-cyclo-2'-deoxyadenosine 2 photoisomerises
      to the (5'R) isomer 1, which is the more easily repaired damage when these
      cyclopurine lesions are formed in DNA.

PMID- 18327335
TI  - Synthesis of a common tetrasaccharide motif of Haemophilus influenzae LPS inner
      core structures.
AB  - A conserved tetrasaccharide structure, L-glycero-alpha-D-manno-heptopyranosyl-(1-
      >2)-(6-O-aminoethylphosphono-L-glycero-alpha-D-manno-heptopyranosyl)-(1-->3)
      [beta-D-glucopyranosyl-(1-->4)]-L-glycero-alpha-D-manno-heptopyranose, from the
      LPS inner core of Haemophilus influenzae has been synthesised as its ethylamino
      glycosides to allow later conjugations. Starting from a previously synthesised
      suitably protected trisaccharide intermediate, the third heptose and subsequently
      the spacer were introduced using thioglycoside donor chemistry. The
      phosphoethanolamine was formed employing a Boc-protected phosphoamidite. Final
      deprotection and conjugation to biotin gave conjugates that will be used to study
      the specificity of MAbs raised against native LPS structures.

PMID- 18327336
TI  - Steric effects of polar substituents evaluated in terms of energy by means of
      isodesmic reactions.
AB  - Steric effects of various polar and some charged groups were estimated on
      sterically crowded cyclopropane cis-1,2-bis derivatives 2 or 3, in which the
      variable substituent is in the proximity of a t-butyl group or of a methyl group.
      The steric energy was evaluated with reference to the pertinent mono derivatives,
      that is as reaction energy of an isodesmic reaction, in which the crowded
      compound is formally synthesized from simple derivatives. Energies were
      calculated within the framework of the density functional theory at level B3LYP/6
      311+G(d,p)//B3LYP/6-311+G(d,p) for 11 dipolar and 5 charged substituents.
      Interaction of charged substituents is not only steric (destabilizing) but also
      inductive (stabilizing). The steric effects evaluated in this way differ
      distinctly from the standard steric constants derived purely from the van der
      Waals radii of the substituents.

PMID- 18327337
TI  - Antioxidant activity of the new thiosulfinate derivative, S-benzyl
      phenylmethanethiosulfinate, from Petiveria alliacea L.
AB  - The antioxidant effects of the new thiosulfinate derivative, S-benzyl
      phenylmethanethiosulfinate (BPT), against the oxidation of cumene and methyl
      linoleate (ML) in chlorobenzene were studied in detail using HPLC. The results
      showed that BPT provided effective inhibition with a well-defined induction
      period under these oxidation conditions, and it was found that the stoichiometric
      factor (n), the number of peroxyl radicals trapped by one antioxidant molecule,
      of BPT is about 2. We then undertook a thorough investigation aimed at
      elucidating the active structural site of BPT. Various model compounds, such as
      diphenyl disulfide, dibenzyl disulfide, S-phenyl benzenethiosulfinate and S-ethyl
      phenylmethanethiosulfinate, were used which provided evidence that the benzylic
      hydrogen of BPT is mainly associated with the peroxyl radical scavenging.
      Moreover, we measured the rate constant for the reaction of BPT with peroxyl
      radicals derived from cumene and ML in chlorobenzene, and based on these
      measurements, BPT reacts with these peroxyl radicals with a rate constant of
      k(inh) = 8.6 x 10(3) and 6.2 x 10(4) M(-1) s(-1), respectively.

PMID- 18327338
TI  - Do garlic-derived allyl sulfides scavenge peroxyl radicals?
AB  - The chain-breaking antioxidant activities of two garlic-derived allyl sulfides,
      i.e. diallyl disulfide (1), the main component of steam-distilled garlic oil, and
      allyl methyl sulfide (3) were evaluated by studying the thermally initiated
      autoxidation of cumene or styrene in their presence. Although the rate of cumene
      oxidation was reduced by addition of both 1 and 3, the dependence on the
      concentration of the two sulfides could not be explained on the basis of the
      classic antioxidant mechanism as with phenolic antioxidants. The rate of
      oxidation of styrene, on the other hand, did not show significant changes upon
      addition of either 1 or 3. This unusual behaviour was explained in terms of the
      co-oxidant effect, consisting in the decrease of the autoxidation rate of a
      substrate forming tertiary peroxyl radicals (i.e. cumene) upon addition of little
      amounts of a second oxidizable substrate giving rise instead to secondary peroxyl
      radicals. The relevant rate constants for the reaction of ROO(.) with 1 and 3
      were measured as 1.6 and 1.0 M(-1) s(-1), respectively, fully consistent with the
      H-atom abstraction from substituted sulfides. It is therefore concluded that
      sulfides 1 and 3 do not scavenge peroxyl radicals and therefore cannot be
      considered chain-breaking antioxidants.

PMID- 18327339
TI  - N-Heterocyclic carbene catalysed beta-lactam synthesis.
AB  - N-Heterocyclic carbenes promote the formal [2+2] cycloaddition of ketenes with N
      tosyl imines to give the corresponding beta-lactams in good to excellent isolated
      yields; chiral NHCs give beta-lactams in high e.e. after crystallisation.

PMID- 18327340
TI  - Promotion of sugar-lectin recognition through the multiple sugar presentation
      offered by regioselectively addressable functionalized templates (RAFT): a QCM-D
      and SPR study.
AB  - The investigation of recognition events between carbohydrates and proteins,
      especially the understanding of how spatial factors and binding avidity are
      correlated, remains a great interest for glycobiology. In this context we have
      investigated by nanogravimetry (QCM-D) and surface plasmon resonance (SPR), the
      kinetics and thermodynamics of the interaction between concanavalin A (Con A) and
      various neoglycopeptide ligands of low molecular weight. Regioselectively
      addressable functionalized templates (RAFT) have been used as scaffolds for the
      design of multivalent neoglycopeptides bearing thiol or biotin functions for
      their anchoring on transducer surfaces. Although these multivalent
      neoglycopeptide ligands cannot span multiple binding sites within the same Con A
      protein, they have increased activities relative to their monovalent counterpart.
      Our results emphasize that the multivalent RAFT ligands function by clustering
      several lectins, which leads to enhanced affinities.

PMID- 18327341
TI  - Bridging the gap between primary and specialist care: formidable challenges
      ahead.

PMID- 18327342
TI  - Public perceptions of healthcare in Singapore.
AB  - INTRODUCTION: Understanding public perceptions of healthcare delivery is
      important to guide policy formulation and practice as well as to identify areas
      where public health communication needs to be strengthened to overcome
      misconceptions and allay unfounded concerns. We conducted a survey of Singapore
      residents to determine perceptions of the affordability and quality of healthcare
      in Singapore. MATERIALS AND METHODS: A sampling frame was drawn from the
      2005/2006 edition of the telephone directory. One thousand seven hundred and
      eighty-three respondents were interviewed via telephone and asked to rank their
      agreement with statements pertaining to healthcare cost and quality on a 5-point
      Likert scale. RESULTS: Respondents were representative of the general population
      in ethnicity and housing type but lower income households were over-represented.
      79.6% of respondents agreed that Singapore had a good healthcare system and 57.5%
      agreed that the government provided good and affordable healthcare to
      Singaporeans. The majority agreed that healthcare was generally affordable,
      especially at polyclinics (78%) and restructured hospitals (50%) and that the
      quality of healthcare in Singapore was high. Comparing primary and tertiary care,
      there was uniformity in the perception of quality at both levels but respondents
      assessed tertiary healthcare to be less affordable (P <0.0001). CONCLUSION:
      Singaporeans are confident in the healthcare system. The quality of Singapore
      healthcare is generally regarded to be high although there are growing concerns
      regarding the affordability of healthcare.

PMID- 18327343
TI  - Concerns, perceived impact and preparedness in an avian influenza pandemic--a
      comparative study between healthcare workers in primary and tertiary care.
AB  - INTRODUCTION: With the potential threat of an avian influenza (AI) pandemic,
      healthcare workers (HCWs) are expected to play important roles, and they
      encounter significant stress levels from an expected increase in workload. We
      compared the concerns, perceived impact and preparedness for an AI pandemic
      between HCWs working in public primary care clinics and a tertiary healthcare
      setting. MATERIALS AND METHODS: An anonymous, self-administered questionnaire was
      given to 2459 HCWs working at 18 public polyclinics (PCs) and a tertiary hospital
      (TH) in Singapore from March to June 2006. The questionnaire assessed work
      related and non-work-related concerns, perceived impact on personal life and work
      as well as workplace preparedness. RESULTS: We obtained responses from 986 PC and
      873 TH HCWs (response rate: 74.6% and 76.7%). The majority in both groups were
      concerned about the high AI risk from their occupation (82.7%) and falling ill
      with AI (75.9%). 71.9% accepted the risk but 25.5% felt that they should not be
      looking after AI patients with 15.0% consider resigning. HCWs also felt that
      people would avoid them (63.5%) and their families (54.1%) during a pandemic. The
      majority expected an increased workload and to feel more stressed at work. For
      preparedness, 74.2% felt personally prepared and 83.7% felt that their workplaces
      were prepared for an outbreak. TH HCWs were more likely to be involved in
      infection-control activities but the perception of infection-control preparedness
      in both groups was high (>80.0%). CONCLUSIONS: HCWs in both public primary and
      tertiary healthcare settings felt prepared, personally and in their workplaces,
      for a pandemic. Their main concerns were risks of falling ill from exposure and
      the possibility of social ostracism of themselves and their families.
      Preparedness levels appeared high in the majority of HCWs. However, concerns of
      HCWs could affect their overall effectiveness in a pandemic and should be
      addressed by incorporating strategies to manage them in pandemic planning.

PMID- 18327344
TI  - Pattern and outcome of subsidised referrals to cardiology specialist outpatient
      clinics.
AB  - INTRODUCTION: Increasing demand for public healthcare and access to specialist
      care has become a major concern. Characterising the referral pattern to a
      national centre's cardiology specialist outpatient clinics (SOCs) and the
      diagnostic outcomes may be useful in formulating referral guidelines to contain
      rising demand. MATERIALS AND METHODS: A prospective observational followup study
      was conducted of all consecutive new patient referrals to the cardiology SOCs of
      the National Heart Centre over a 1-month period. The records of these 1224
      patients were reviewed following their first visit and again after 3 months of
      evaluation and investigation. Patients' demographics, referral sources,
      indications of referral, risk factors, provisional and final diagnoses were
      collected. Referrals from the top 2 volume sources (government polyclinics and
      hospital Emergency Department) accounted for 600 referrals. These subsidised
      referrals formed the study group for analysis. RESULTS: The mean age of referred
      patients was 56 +/- 15.2 years, with equal proportion of males and females. Most
      patients had known cardiac risk factors of hypertension (53.2%) and
      hyperlipidaemia (42.3%). Only 23% of referrals had significant cardiac
      abnormalities. Referrals for typical chest pain derived the highest yield whereas
      referrals for atypical chest pain, non-cardiac chest pain derived the lowest
      yield. Referrals for asymptomatic electrocardiogram (ECG) changes (except for
      atrial flutter/fibrillation) did not yield cardiac abnormalities. Multivariate
      analysis of chest pain referrals showed typical chest pain and hyperlipidaemia to
      be statistically significant predictors for coronary artery disease. CONCLUSION:
      Referrals to cardiology outpatient specialist clinics should be based on the
      presence of patient symptoms, particularly that of typical chest pain. In
      asymptomatic patients, routine ECG screening did not appear to yield significant
      cardiac abnormalities.

PMID- 18327345
TI  - Consequences of right siting of endocrinology patients--a financial and caseload
      simulation.
AB  - INTRODUCTION: Right siting has been actively advocated to mitigate rising
      healthcare costs as well as to free up tertiary resources for the provision of
      care to more complex patients, research and education. There are, however,
      concerns that in a block budget setting right siting will reduce patient volumes,
      thus impacting on subsequent funding allocations and also patient revenues. We
      sought to determine through modelling and simulation the financial and volume
      impacts of right siting of endocrinology outpatients in a large tertiary hospital
      in Singapore. MATERIALS AND METHODS: Data were collected prospectively on patient
      casemix including complexity (complex defined as requiring specialist care), time
      required for consultations and revenues garnered. The data were used to simulate
      2 scenarios: right siting of all simple cases with freed up resources directed to
      research and teaching (research scenario) and right siting of all simple cases
      with replacement by complex cases (service scenario). RESULTS: The department
      sees an estimated 33,000 outpatients per year with a total annual outpatient
      revenue of $8.6 million. The research scenario would see a decline in patient
      volume to 11,880 cases per year which would result in a corresponding decrease in
      revenue of $5 million and freeing up of 2.8 hours/ week for each staff. The
      service scenario yields a drop in patient volume of 9500 per annum and a drop in
      revenue of $1.9 million. CONCLUSION: Right siting reduces tertiary care patient
      volumes and revenues and may discourage right siting efforts. A viable business
      model for the tertiary institutions is needed to facilitate support for right
      siting.

PMID- 18327346
TI  - Impact of the Singapore National Asthma Program (SNAP) on preventor-reliever
      prescription ratio in polyclinics.
AB  - INTRODUCTION: The Singapore National Asthma Program (SNAP) was launched in 2001
      to address the high burden of asthma in Singapore. One component of the SNAP was
      directed at improving asthma control in the community by promoting preventive
      treatment with inhaled corticosteroids. This paper describes the program on
      prescription patterns of preventor and reliever medication for asthma in the
      polyclinics. MATERIALS AND METHODS: We monitored the prescription pattern for
      asthma as the preventor-reliever (PR) drug ratio. The PR ratio was employed both
      as a positive feedback tool and as a key performance indicator (KPI) for the
      program. Individual clinics were encouraged to implement locally relevant and
      effective initiatives to increase the KPI and facilitate this process. The
      different methods included chronic care models, multidisciplinary teams, enhanced
      primary care clinics, pre-counselling screening, decision support tools, self
      management support, a patient information system and community education.
      RESULTS: In the course of the program, the case load for asthma in the
      polyclinics increased by 31%. During the same period, the average PR ratio
      increased significantly from 0.68 to 1.80 (P <0.001). CONCLUSIONS: A simple audit
      and positive feedback program based on PR ratios, accompanied by sustained local
      quality improvement cycles has been associated with a significant shift in the
      drug treatment of asthma away from episodic quick relief medication towards long
      term daily preventive treatment with inhaled steroids in polyclinics.

PMID- 18327347
TI  - Bridging the gap between primary and specialist care--an integrative model for
      stroke.
AB  - Stroke is a major cause of death and disability in Singapore and many parts of
      the world. Chronic disease management programmes allow seamless care provision
      across a spectrum of healthcare facilities and allow appropriate services to be
      brought to the stroke patient and the family. Randomised controlled trials have
      provided evidence for efficacious interventions. After the management of acute
      stroke in a stroke unit, most stable stroke patients can be sent to their family
      physician for continued treatment and rehabilitation supervision. Disabled stroke
      survivors may need added home-based services. Suitable community resources will
      need to be harnessed. Clinic-based stroke nurses may enhance service provision
      and coordination. Close collaboration between the specialist and family physician
      would be needed to right-site patients and also allow referrals in either
      direction where necessary. Barriers to integration can be surmounted by trust and
      improved communication. Audits would allow monitoring of care provision and
      quality care enhancement. The Wagner model of chronic care delivery involves self
      management support, shared clinical information systems, delivery system
      redesign, decision support, healthcare organisation and community resources. The
      key and critical feature is the need for an informed, activated (or motivated)
      patient, working in collaboration with the specialist and family physician, and a
      team of nursing and allied healthcare professionals across the continuum of care.
      The 3-year Integrating Services and Interventions for Stroke (ISIS) project
      funded by the Ministry of Health will test such an integrative system.

PMID- 18327348
TI  - Providing integrated mental health services in the Singapore primary care setting
      -the general practitioner psychiatric programme experience.
AB  - INTRODUCTION: The aim of our programme was to right site a selected group of
      patients to the care of the primary sector for follow-up management. Mental
      disorders are recognised as a major public health problem worldwide which places
      an enormous burden on health services. Patients on treatment in the hospitals are
      largely managed by specialists either in the restructured hospitals or in private
      practice with minimal involvement of general practitioners (GPs). Yet, there are
      many patients with chronic mental illnesses who are stable, require maintenance
      medications and are best managed in the community. STRATEGIES: GPs were given
      appropriate training and support to help them manage patients with mental
      illnesses in their clinics. The training involved in-depth, comprehensive
      training on mental illness, providing the GPs with the skills necessary to manage
      the stable patients within the community. It also facilitated Early Detection
      Intervention by enhancing the GPs capabilities to detect and manage the mentally
      ill. Patients screened by psychiatrists who fulfill the referral criteria agreed
      upon by both the specialist team and the GP partners were referred to the GPs
      with initial support from case managers when required. The benefits to patients
      include: increased convenience, savings in terms of transport costs and travel
      time, the flexibility of being seen during after office hours, less stigma and
      the option of managing their other medical conditions, if any, by the same
      doctor. RESULTS: To date, a total of 200 patients have been successfully referred
      to the 30 GPs in the programme. This represents an average savings of more than
      1000 consultation visits to the hospital per year. CONCLUSION: The programme
      allows for the right siting of care for patients and allows the hospital to
      channel precious resources to more appropriate uses.

PMID- 18327349
TI  - Family medicine education in Singapore: a long-standing collaboration between
      specialists and family physicians.
AB  - In many countries, family medicine (FM) training has been conducted mainly by
      senior family physicians alone. However, FM training in Singapore in the last 30
      years has involved specialists working in close collaboration with family
      physicians. The areas in which specialists are currently involved include the
      training of FM trainees in tertiary hospitals, the Master of Medicine in Family
      Medicine [MMed (FM)] and Graduate Diploma in Family Medicine (GDFM) programmes.
      This close relationship has been crucial in the continuing vocational and
      professional development of family physicians and in fostering closer
      collaboration between family physicians and specialists, thus ultimately
      benefiting patient care.

PMID- 18327350
TI  - Medication use in the transition from hospital to home.
AB  - After hospital discharge, correct understanding and use of medications are key
      components of patient safety. The current discharge process does not provide
      adequate fail-safes to ensure quality post-discharge care. This often leads to
      preventable medication errors as well as nonadherence. Several barriers to
      successful discharge counselling, including use of medical jargon, lack of
      educational and administrative resources, time constraints, and low health
      literacy, contribute to ineffective communication between hospital physicians and
      patients. Other obstacles include inaccurate or incomplete documentation of the
      medication history, lack of social support, financial constraints, and poor
      transfer of information to outpatient physicians. Solutions to improve medication
      use in the transition period after hospital discharge require effective
      communication with patients through the use of easily understood language,
      highlighting key information, and ensuring patient comprehension through the
      "teach back" technique. More timely communication with outpatient physicians in
      addition to a more comprehensive transfer of information further facilitates the
      transition home. Finally, a systematic process of medication reconciliation also
      aids in decreasing the incidence of medication errors. Hospital-based physicians
      who attend to key details in the process of discharging patients can have a
      profound impact on improving medication adherence, avoiding medication errors,
      and decreasing adverse outcomes in the post-discharge period.

PMID- 18327351
TI  - Internationally, it is time to bridge the gap between primary and secondary
      healthcare services for the dying.
AB  - Around two-thirds of people with incurable diseases in economically developed
      countries wish to die at home, but less than one-third succeed in doing so.
      Developing primary care-based services for the dying in the community is
      essential to reach and serve the whole population. Three typical "trajectories"
      or patterns of decline in the last year(s) of life have recently been described,
      and each of these may require different models of care to best meet the needs of
      patients. The palliative care approach must be urgently extended to patients with
      non-malignant conditions who have comparable concerns to and in some cases even
      greater and more prolonged unmet needs than cancer patients. Primary care
      professionals have the potential and ability to provide end-of-life care for most
      patients, given adequate training, resources and access to care facilities and
      specialist advice when needed. They are ideally placed to identify patients at
      diagnosis, hospital discharge or disease progression who might benefit from an
      early palliative care approach. In the UK, Australia and US, some important
      initiatives are gaining momentum to facilitate the delivery of primary palliative
      services. In Singapore, the involvement of family physicians in end-of-life care
      is very low. A local survey is currently being conducted to identify the
      challenges in getting more family physicians involved. Given adequate time and
      resources, community professionals throughout the world can provide effective,
      equitable, and accessible primary palliative care, and form a solid bridge of
      communication and support between primary and secondary care.

PMID- 18327352
TI  - The hospitalist movement--a complex adaptive response to fragmentation of care in
      hospitals.
AB  - The increasing complexity of healthcare is accelerating the rate of
      specialisation in medicine, which in turn aggravates the fragmentation of care in
      hospitals. The hospitalist movement advocates for the return of generalist
      physicians to the hospital to provide general and more holistic medical care to
      inpatients. This can be seen as an adaptive response to care fragmentation.
      Starting in the mid-1990s in North America, where the impact of healthcare
      complexity and fragmentation has been most widely felt, the hospital movement has
      gained strength and spread across the continent rapidly. This paper examines the
      phenomenon of the hospitalist movement in the United States, Canada and
      Singapore. The conclusion is that variants of the hospital movement may emerge in
      different parts of the world as healthcare systems adapt to common global trends
      that drive the increasing complexity of healthcare.

PMID- 18327353
TI  - Improving access to outpatient cardiac care at the national heart centre--a
      partnership between specialists and primary care.
AB  - Ensuring timely access to specialist care is an important indicator of the
      quality of a health service. Demand for cardiology outpatient appointments has
      grown considerably in the last decade, leading to increased waiting time for
      cardiology appointments at public hospitals. This paper examines the
      effectiveness of past and ongoing strategies initiated by the National Heart
      Centre, many of which were in collaboration with SingHealth Polyclinics,
      documents the lessons learnt, and provides a framework for approaching this
      problem. Instead of a simplistic approach where institutions react to long
      waiting times by growing capacity to meet demand, this paper emphasises the need
      to focus on the final intended outcome (timely diagnosis and treatment) rather
      than on a single performance indicator, such as waiting time. A broad systems
      approach at the national level is advocated, rather than piecemeal, uncoordinated
      actions by individual hospitals.

PMID- 18327354
TI  - Bridging the gap between occupational medicine and family medicine.
AB  - Family medicine and occupational medicine share close similarities in their focus
      on disease prevention and health promotion. The opportunities for mutual learning
      and collaboration in patient care abound, with far-reaching implications on the
      standard of patient care that can be offered. Unfortunately, a gap exists between
      family medicine and occupational medicine in dayto- day practice as well as in
      continuing medical education. It is important that we actively seek to bridge
      this gap. The workforce constitutes a significant part of the population and thus
      the patient load of a typical primary healthcare practice. Moreover, with an
      ageing population and rising retirement age, we can expect that there will be an
      increasing number of health issues to be addressed among older working people.
      Both occupational and non-occupational factors are important in determining an
      individual's health. Thus, family physicians need to adequately understand
      occupational medicine and vice versa.

PMID- 18327355
TI  - Natural product and drugs interactions, its clinical implication in drug therapy
      management.
AB  - The interaction of natural products and drugs is a common hidden problem
      encountered in clinical practice. The interactions between natural products and
      drugs are based on the same pharmacokinetic and pharmacodynamic principles as
      drug-drug interactions. Clinically important interactions appear to involve
      effects on drug metabolism via cytochrome P-450 isoenzymes, impairment of hepatic
      or renal function, and other possible mechanisms. To effectively counsel patients
      on interactions involving natural products, physicians, and pharmacists should be
      familiar with the most commonly used products, and have access to information on
      more obscure products. In this review, we describe details of drugs interaction
      with natural products and its impact on drug therapy management.

PMID- 18327356
TI  - Effects of vitamin D in lung, stomach, esophagus and testis tissues following
      administration of urethane in balb/c mice.
AB  - OBJECTIVE: To elucidate the role of vitamin D in the histopathological
      alterations process and K-ras gene mutation exon 1 of tissues including lung,
      stomach, esophagus, and testis, by the administration of urethane. METHODS: An
      experimental study in inbred balb/c mice aged 9-11 weeks was designed. This
      investigation was performed from 2003 to 2005 in the Department of Medical
      Genetics, Medical Sciences/University of Tehran, Tehran, Iran. The samples were
      classified into 3 groups: the urethane group was characterized by intraperitoneal
      injection of 3 times urethane (600 mg/kg/day at 48 hour intervals). The second
      group U+D was given 3.5 mg/kg (6.3 mg/1000 ml) vitamin D in the drinking water
      for 4 weeks following the same intake of urethane as the first group, and the
      third one was the control group. All mice were sacrificed after 20 weeks, tissues
      were removed and examined for histopathological changes and mutations in the exon
      1 of the K-ras gene. RESULTS: Thirty mice were studied. The formation of lung
      tumor was, significantly, increased in the urethane group as compared with the
      control group (p<0.005), however, such a difference was not found in the U+D and
      control groups. In addition, there was no significant difference between all
      groups in other examined tissues. There was no mutation in the exon 1 of K-ras
      gene of the lung adenomas, adenocarcinomas, and stomach metaplasia. CONCLUSION:
      Our results showed the anti-tumorigenic effect of vitamin D3 in lung tumors
      induced by urethane. Vitamin D may reduce the risks of a tumorigenic diet that
      includes high fermented foods and beverages that produce urethane in their
      process.

PMID- 18327357
TI  - Trace elements and flapping tremors in patients with liver cirrhosis. Is there a
      relationship?
AB  - OBJECTIVE: To investigate the possible correlation between hepatic flapping
      tremors and serum manganese Mn, iron Fe, zinc Zn, and copper Cu. METHODS: This
      case control study was carried out in Assiut University Hospital, Assiut, Egypt
      from June 2006 to June 2007. It included 100 patients with liver cirrhosis, 78
      had flapping tremor, and 22 had not, and 60 healthy controls. All patients were
      subjected to assessment of serum Mn, total Fe, total iron binding capacity
      (TIBC), Zn, and Cu. Assessment of hepatic encephalopathy was carried out using a
      battery of cognitive function tests. All patients had electroencephalography and
      MRI of the brain. RESULTS: Compared to healthy controls, patients showed increase
      in Mn (p<0.0001), Cu (p<0.05) and decrease in TIBC (p<0.000), Zn (p<0.05). Eighty
      two percent of patients had minimal hepatic encephalopathy (mHE). In 85%, MRI
      brain showed bilateral hyperintense substantia nigra and globus pallidus on T1
      weighted images. A significant positive correlation was present between tremors
      and severity of liver dysfunction, mHE and serum Cu, and negative correlation
      with total Fe, TIBC, and Zn. CONCLUSION: Altered homeostasis of Mn and other
      minerals could be responsible for the pathophysiology of cognitive deficits
      associated with liver cirrhosis, but not with flapping tremors. The exact
      pathogenic role and possibilities for therapeutic implications need further
      study.

PMID- 18327358
TI  - The role of surface ECG and transthoracic echocardiography for predicting
      postoperative atrial fibrillation after coronary artery bypass surgery.
AB  - OBJECTIVE: To evaluate the roles of surface electrocardiogram (ECG) and
      transthoracic echocardiography (ECHO) for prediction of atrial fibrillation (AF)
      after coronary artery bypass grafting (CABG). METHODS: This study was conducted
      from 2002-2004 at the Cardiovascular Department of Hacettepe University, Ankara,
      Turkey. Seventy consecutive patients were enrolled in this study that underwent
      elective CABG. A 12-lead ECG was recorded one day before cardiac surgery and was
      repeated during the 5 days after CABG. P-wave dispersion (PWD) was defined as the
      difference between maximum and minimum P-wave duration. Differences in P-wave
      duration were compared between the pre- and postoperative 12-lead ECG
      measurements. RESULTS: Postoperative AF developed in 17 (24%) cases of 70
      patients. The PWD was found to be significantly higher in patients with AF
      preoperatively (60+/-19 versus 47+/-13, p=0.003), postoperative first day (56+/
      12 versus 44+/-11, p<0.002) and fifth day (51+/-29 versus 41+/-11, p<0.001).
      Patients with AF were significantly older, the mean age of the AF group was (68+/
      7) years and of the sinus rhythm (SR) group was (59+/-10 years) (p<0.001). The AF
      group had left ventricular systolic dysfunction (56+/-13% versus 56+/-8%,
      p=0.042, preoperatively; 49+/-8% versus 60+/-10%, p=0.001, postoperatively) and a
      larger left atrium (46+/-5 versus 39+/-5 mm, p<0.001, preoperatively and 44+/-7
      versus 39+/-5 mm, p=0.046, postoperatively) than the SR group. CONCLUSION: This
      prospective study demonstrated that PWD on surface ECG and additional
      echocardiographic parameters are simple and reliable indexes to predict the
      development of AF after CABG.

PMID- 18327359
TI  - Prolongation of AV nodal refractoriness by Ruta graveolens in isolated rat
      hearts. Potential role as an anti-arrhythmic agent.
AB  - OBJECTIVE: To evaluate concentration-dependent effects of total extract of Ruta
      graveolens and its purified alkaloid fraction on the nodal basic and functional
      properties. METHODS: In the present experimental study, we used the Langendorff
      model for perfusion of isolated rat hearts to determine the effects of various
      concentrations of methanolic extract of Rue (1.25 x 10(-6) % weight per volume
      percent [W/V]; 2.5 x 10(-6) % W/V; 3.75 x 10(-6) % W/V) and total alkaloid of Rue
      (0.25 x 10(-6) % W/V; 0.5 x 10(-6) % W/V) on electrophysiological properties of
      cardiac tissue. Selective stimulation protocols were used to independently
      quantify atrioventricular AV nodal recovery, facilitation, and fatigue. We used 3
      groups (N=24) of isolated perfused rat AV nodal preparations to assess the effect
      of Rue extracts. The study was carried out in October 2006 in the
      electrophysiology laboratory of the Cardiovascular Research Center of Golestan
      University of Medical Sciences, Golestan, Gorgan, Iran. RESULTS: Our results
      showed that both the total plant extract and the alkaloid fraction of Ruta
      graveolens had a similar trend of action on nodal conduction time and
      refractoriness. Furthermore, we observed increased atrioventricular conduction
      time (83+/-4 to 108+/-5) msec and functional refractory period (157.6+/-3 to
      163.7+/-4 msec) at a maximum concentration of 3.75 x 10(-6) % W/V. CONCLUSION:
      The above results indicated a potential antiarrhythmic effect of Ruta graveolens
      in treating supra ventricular tachyarrhythmia.

PMID- 18327360
TI  - Plasma homocysteine level in cardiac syndrome X and its relation with duke
      treadmill score.
AB  - OBJECTIVE: To investigate the plasma homocysteine level and the relationship
      between plasma homocysteine level and duke treadmill score (DTS) in cardiac
      syndrome X (CSX) patients. METHODS: Seventy-nine patients (36 male, 43 female,
      mean age: 50 +/- 8.8 years) admitted to Gazi University Hospital, Ankara, Turkey
      with typical effort angina, positive stress test, and angiographically normal
      coronary arteries between January and September 2006 were included in this
      prospective and controlled study. Thirty asymptomatic patients (11 male, 19
      female, mean age: 47.6 +/- 8.3 years) with 2 cardiovascular risk factors were
      chosen as a control group. Plasma homocysteine level was measured in both groups
      and DTS was calculated in the CSX group. Plasma homocysteine was measured with
      the AxSYM homocysteine immunoassay method in both groups. RESULTS: Plasma
      homocysteine level was higher in the CSX group compared to the control group
      (16.5 +/- 4.9 micromol/L, n=79, versus 12.4 +/- 4.1 micromol/L, n=30, p<0.001).
      The DTS was -2.7 +/- 5.3 in the CSX group. There was a negative correlation
      between the DTS and homocysteine levels in the CSX group. (r= -0.506, p<0.001).
      CONCLUSION: Plasma homocysteine level, which is known to cause endothelial
      dysfunction and microvascular ischemia were higher in CSX patients. Also, this
      increase in homocysteine level inversely correlated with the DTS, which
      represents the magnitude of ischemia.

PMID- 18327361
TI  - Urinary trypsin inhibitor treatment ameliorates acute lung and liver injury
      resulting from sepsis in a rat model.
AB  - OBJECTIVE: To evaluate the protective effect of urinary trypsin inhibitor (UTI)
      on acute lung and liver injury in rat model induced by sepsis with infra
      abdominal infection. METHODS: This study was performed in the University of
      Wuhan, Wuhan, China in May 2007. Sepsis models were made by cecal ligation and
      puncture (CLP) in Sprague-Dawley rats. Forty rats were randomly divided into
      sham, CLP, CLP/UTI I (20 u/g) and CLP/UTI II (50 u/g) groups, with 10 rats in
      each. All of them were sacrificed 12 hours after CLP. The mean arterial pressure
      (MAP), heart rate (HR), the wet-to-dry lung weight ratio (W/D) was measured and
      venous blood was collected for assaying tumor necrosis factor-alpha (TNF-alpha),
      interleukin-10 (IL-10), alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and lactic acid. Superoxide dismutase (SOD),
      malondialdehyde (MDA) and expression of inducible nitric oxide synthase (iNOS)
      mRNA in lung and hepatic tissues were examined. RESULTS: Compared with the CLP
      group, MAP and HR in 50 u/g UTI treated rats was stable (p<0.01). Marked
      elevation levels of W/D ratio were lowered after administration of 50 u/g UTI
      (p<0.01). Treatment with 50 u/g UTI prevented marked elevation in MDA, ALT, AST,
      TNF-alpha, lactic acid levels, expression of iNOS mRNA, and elevated IL-10 and
      SOD activity (p<0.01). CONCLUSION: Urinary trypsin inhibitor has a protective
      effect against sepsis. Its action mechanisms are probably involved in the
      inhibition of inflammatory factor production and suppression of lipid
      peroxidation and iNOS mRNA expression.

PMID- 18327362
TI  - Comparison of the effectiveness of pretreatment by fentanyl and remifentanil on
      rocuronium induced injection pain.
AB  - OBJECTIVE: To compare the efficacy of fentanyl and remifentanil as prodrugs in
      the prevention of rocuronium injection pain by using a control group. METHODS: In
      a randomized, double-blinded, controlled study, 102 adult patients aged between
      18-60 undergoing elective surgery under general anesthesia and classified into
      American Society of Anesthesiologists (ASA) I and ASA II risk groups were
      included in the study. The study was carried out from July 2005 to April 2006 at
      Dokuz Eylul University, Izmir, Turkey. Unpremedicated patients were randomly
      allocated to one of 3 groups. Patients received 2 mL (0.02 mg) of remifentanil (n
      =34), 2 mL of fentanyl 0.1 mg (n =34), and 2 mL of saline (n =34), by injection
      over 10 seconds. Thirty seconds after prodrug administration, 10 mg (10 mg/mL)
      intravenous rocuronium bromide was administered over 5 seconds and pain
      assessment was performed by using a 5-point scale. RESULTS: When the 3 groups of
      34 patients were compared in terms of pain assessment scoring, a statistically
      significant difference was determined (p=0.02). When the groups were paired, it
      was seen that this difference resulted from the remifentanil and saline groups
      (p=0.02). CONCLUSION: This study shows that a bolus dose of 0.02 mg of
      remifentanil is a more effective prodrug administration compared to the
      application of saline, however, remifentanil and fentanyl have no superiority
      over one another and the administration of fentanyl is equally effective as
      saline prodrug administration.

PMID- 18327363
TI  - Placebo controlled comparison of the opioid sparing effect of meloxicam and
      diclofenac after abdominal hysterectomy.
AB  - OBJECTIVE: To compare the opioid sparing effect of meloxicam, diclofenac, and
      placebo after abdominal hysterectomy. METHODS: This study was conducted at the
      Riyadh Military Hospital, Riyadh, Kingdom of Saudi Arabia from February 2004 to
      November 2006. Women of American Society of Anesthesiologist's classification I
      or II of ages 25-60 years scheduled for abdominal hysterectomy were included.
      Those with significant systemic disease or contraindication to opioid or non
      steroidal anti-inflammatory drugs were excluded from the study. All patients
      received general anaesthesia and intravenous (IV) morphine, and were intubated
      and ventilated for the operation. The patients were randomized and rectally
      received meloxicam 15 mg, diclofenac 100 mg, or placebo suppository. Patients,
      anesthetists, and nurses managing the patients postoperatively were blinded to
      these drugs. In the recovery room, IV patient controlled morphine was commenced.
      The information sought included patient characteristics age, weight, duration of
      operation, and doses of morphine consumed in 24 hours. RESULTS: Seventy-five
      patients 25 in each group participated in this study and only 5 patients dropped
      out. There was no difference in age and body weight of the patients, and duration
      of the operation. All underwent either total or sub-total hysterectomy. The mean
      SD morphine consumption in the 24-hour postoperative period was 37.7 (11.1) mg
      for the diclofenac group, 40.1 (7.8) mg for the meloxicam group, and 45.2 (9.8)
      mg for the placebo group. As compared to placebo, the mean morphine consumption
      in diclofenac but not in meloxicam group was significantly (p<0.05) reduced.
      CONCLUSION: Our study demonstrates a significant opioid sparing effect after
      abdominal hysterectomy with diclofenac, but not with meloxicam.

PMID- 18327364
TI  - Efficacy of the latanoprost versus timolol/dorzolamide combination therapy in
      patients with primary open angle glaucoma.
AB  - OBJECTIVE: Efficacy of the latanoprost versus timolol/dorzolamide combination
      therapy in patients with primary open angle glaucoma METHODS: The study was
      designed as a 6 months randomized, observer-masked study comprising 120 patients
      with primary open-angle glaucoma in Feiz Hospital, Isfahan, Iran, from 2006 to
      2007. The patients were randomized (latanoprost, n = 60; dorzolamide/timolol, n =
      60) to treatment with either latanoprost, 0.005% once daily, or the combination
      of timolol 0.5% twice daily, and dorzolamide 2% 3 times daily. The mean
      intraocular pressure (IOP) after one, 3, and 6 months of treatment was compared
      with baseline in the 2 groups. RESULTS: A total of 120 patients were randomized
      to 2 equal treatment groups. The mean baseline IOP values were similar between
      the 2 groups. The mean (standard error of mean [SE]) IOP reductions at months one
      was 7.2 (0.4), at month 3 was 7.3 (0.4), and at month 6 was 7.1 (0.3) mm Hg for
      the latanoprost group and 7.5 (0.3), 7.8 (0.3), and 7.4 (0.3) mm Hg for the
      dorzolamide/timolol group. The 2 therapies were similarly effective. CONCLUSION:
      The latanoprost and dorzolamide/timolol combination were equally effective at
      lowering IOP compared to untreated baseline.

PMID- 18327365
TI  - Molecular detection and antimicrobial resistance of diarrheagenic Escherichia
      coli strains isolated from diarrheal cases.
AB  - OBJECTIVE: To identify and classify Iranian isolates of diarrheagenic Escherichia
      coli (E. coli) on the basis of presence of virulence genes and to determine
      antibiotic susceptibility of isolated strains. METHODS: The current cross
      sectional study was conducted in 2005 at the Pasteur Institute, Tehran, Iran. One
      hundred and ninety-three diarrheagenic E. coli isolated from diarrheal patients
      in different regions of Iran were included in current study. Virulence factor
      genes for diarrheagenic E. coli were detected by polymerase chain reaction.
      RESULTS: Of the 193 diarrheagenic E. coli detected by PCR, 86 (44.5%) were Shiga
      toxin-producing E. coli STEC, 74 (38.4%) enteropathogenic E. coli EPEC, 19 (9.8%)
      enteroaggregative E. coli, and 14 (7.3%) enterotoxigenic E. coli isolates.
      Susceptibility to 12 clinically important antimicrobial agents was determined for
      193 strains of diarrheagenic E. coli. A high incidence of resistance to
      tetracycline (63%), ampicillin (62%), streptomycin (56%), amoxicillin/clavulanic
      acid (44.5%), trimethoprim/sulfamethoxazole (39.5%), and cephalothin (37%) was
      observed. CONCLUSION: The STEC and EPEC strains with high resistance to
      tetracycline and ampicillin, but highly susceptible to quinolones are among the
      most important causative agent of diarrhea in Iran. This study suggests that
      antimicrobial resistance is widespread among E. coli strains colonizing Iranian
      patients. Guidelines for appropriate use of antibiotics in developing countries
      require updating.

PMID- 18327366
TI  - An inverse relation between CagA+ strains of Helicobacter pylori infection and
      risk of erosive GERD.
AB  - OBJECTIVE: The aim of this study is investigating the association of Helicobacter
      pylori (H. pylori) infection and its cytotoxic-associated gene A (cagA) strain
      with reflux esophagitis. METHODS: In a case-control setting (May 2005-2006),
      patients with reflux esophagitis (case group) were compared with age and gender
      matched people suffering from symptoms of gastroesophageal reflux disease with
      normal upper gastrointestinal endoscopic findings (control group) in Imam
      Khomeini Hospital, Tabriz, Iran. The rates of H. pylori and its cagA positive
      infections were separately compared between the 2 groups and the subgroups with
      different severity of reflux esophagitis. RESULTS: Ninety-two and 93 patients
      were enrolled in the case and the control groups. The rate of H. pylori infection
      was insignificantly lower in the case group (81.5% versus 87.10%, p=0.29, odd
      ratio 0.654, 95% Confidence interval [CI] 0.293 to 1.495). The CagA positive
      infections were found significantly more frequent in the control group (59.1%
      versus 40.2%, p=0.01, odd ratio 0.465, 95% CI 0.258 to 0.836). There was no
      significant difference between the severity subgroups of the disease for H.
      pylori (p=0.30) or cagA positive infection rates (p=0.40). CONCLUSION: The CagA
      positive strains might have a protective effect against reflux esophagitis.

PMID- 18327367
TI  - The effect of arthroscopic surgery and intraarticular drug injection to the
      antioxidation system and lipid peroxidation at osteoarthritis of knee.
AB  - OBJECTIVE: To elucidate the effects of arthroscopy and intraarticular hyaluronan
      therapies on antioxidant enzyme activity and lipid peroxidation. METHODS: This
      study was conducted between January and May 2005, at the Department of
      Orthopedics and Traumatology, Suleyman Demirel University, Isparta, Turkey. A
      total of 60 patients with knee pain who were diagnosed as knee osteoarthritis
      according to the American College of Rheumatology (ACR) criteria were included in
      this study and randomly and equally divided into 4 groups. Intraarticular Hylan G
      F 20 treatment was given to group 1 for 3 weeks. Intraarticular Hylan G-F 20
      treatment plus oral vitamin E were administered to group 2 for 3 weeks. Only
      arthroscopy treatment was applied to the control group (group 3). Intraarticular
      Na-hyaluronate treatment was given to group 4 for 5 weeks. Blood and synovial
      fluid samples were taken from all the patients for biochemical analysis, and the
      following parameters were measured: superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx), and malondialdehyde (MDA). RESULTS: There was no
      significant difference in blood SOD, CAT, GPx levels, and synovial SOD and GPx
      levels in groups treated with hyaluronan, when compared with the controls.
      However, there was a significant change in MDA levels in synovial fluid samples
      of group 1, group 2, and group 4, when compared with the controls. CONCLUSION: In
      knee osteoarthritis, intraarticular hyaluronan therapy following arthroscopy may
      diminish lipid peroxidation in synovial fluid.

PMID- 18327368
TI  - Perinatal and neonatal outcomes of growth restricted fetuses with positive end
      diastolic and absent or reversed umbilical artery doppler waveforms.
AB  - OBJECTIVE: To evaluate the outcome of intrauterine growth restriction fetuses
      with absent or reversed end-diastolic flow in the umbilical artery. METHODS: This
      was a retrospective study conducted at the Department of Maternal Fetal Medicine
      of the Bakirkoy Women and Children's Teaching Hospital, Istanbul, Turkey between
      2002 and 2006. Three hundred and ten pregnant women with growth-restricted
      fetuses confirmed by ultrasound were followed up with Doppler studies of the
      umbilical artery. The population was subdivided into 2 groups. Group 1,
      intrauterine growth restriction with positive end diastolic flow velocity
      waveforms, (n=137) and group 2, intrauterine growth restriction with absent or
      reversed end diastolic velocities, (n=163). Perinatal and neonatal outcomes of
      the 2 groups were recorded. RESULTS: Group 1 was associated with a higher
      perinatal mortality and morbidity rate than group 2 (p=0.02), odds ratio [OR]:
      1.09, 95% confidence interval [CI] 1-3.5, (p=0.03, OR: 2, 95% CI 1.2-3.2). In
      group 1, significantly more neonates were admitted to the neonatal intensive care
      unit, but no difference was seen in neonatal intensive care unit stay. The
      frequency of respiratory distress syndrome, septicemia, and necrotizing
      enterocolitis increased in group 1. There was no significant difference in need
      for ventilation of respiratory distress syndrome. CONCLUSION: Our data suggest
      that pregnancies with absent or reversed end-diastolic flow in the umbilical
      arteries have high perinatal mortality and morbidity.

PMID- 18327369
TI  - Reference ranges for lymphocyte subsets in healthy adult male Omanis.
AB  - OBJECTIVE: To determine the reference ranges of lymphocyte subsets in
      serologically HIV-seronegative healthy male adults in Oman. METHODS: A cohort, of
      118 healthy male blood donors ranging in age from 18-51 years, was included in
      the study. The average age was 25 years. Blood samples collected into tubes
      containing ethylene-diamine-tetra acetic acid were investigated for lymphocyte
      subsets using flow cytometer. This study was conducted in the Immunology
      Laboratory of the Sultan Qaboos University, College of Medicine and Health
      Sciences, Muscat, Oman during the year 2006. RESULTS: For the 118 males
      investigated, the mean percentage and absolute values of the lymphocyte subsets
      were as follows: CD3: 68.53 +/- 7.5%, 1701 +/- 489 cells/microliter; CD4: 40.4 +/
      6.5%, 1006 +/- 319 cells/microliter; CD8: 25.8 +/- 5.9%, 638 +/- 225
      cells/microliter; CD19: 13.7 +/- 4.7%, 349 +/- 158 cells/microliter, and CD56:
      12.2 +/- 6.7%, 308 +/- 204 cells/microliter. The ratio of CD4/CD8 was 1.6.
      CONCLUSION: Immunophenotyping has been used to establish reference values of
      lymphocyte subsets in normal healthy adult males in Oman. The Omani male
      reference values obtained in this study show wide variations compared with kits
      values previously used as a reference.

PMID- 18327370
TI  - Clinicopathological pattern of malignant parotid gland tumors in Saudi Arabia.
AB  - OBJECTIVE: To report our experience of varied presentations and diverse
      histopathological spectrum of parotid gland malignancies. METHODS: This
      retrospective analysis incorporated patients with histological evidence of
      malignant parotid tumors at King Khalid University Hospital, Riyadh, Saudi Arabia
      over a 20-year period from 1984 through 2004. The medical records of these
      patients were analyzed for their demographic characteristics, clinical features,
      operations performed, and pathological diversity. RESULTS: Thirty-two patients
      comprised this study group. There is a male preponderance over females with a
      ratio of 2.2:1 (22 men and 10 women) and mean age of 51.8 (range 28-81 years). A
      painless lump was the most frequent clinical manifestation observed in 23 (71.8%)
      patients followed by facial nerve dysfunction in 14 (43.7%) patients.
      Parotidectomy was performed in 22 (68.7%) patients: 16 superficial and 6 total. A
      partial facial nerve sacrifice was undertaken in 14 (43.7%), and total nerve
      sacrifice in 9 (28.1%) patients. Four (12.5%) patients presented with cervical
      lymph node metastases necessitating radical neck dissection. Nine (28.1%)
      patients had mucoepidermoid carcinoma, 8 (25%) adenoid cystic carcinoma, 6
      (18.7%) adenocarcinoma, not otherwise specified, and 2 (6.2%) were reported to
      have carcinoma in pleomorphic adenoma. Twenty (62.5%) specimens revealed high
      grade aggressive lesions, and out of these, 19 (59.3%) patients presented with
      stage III/IV disease. CONCLUSION: Malignant parotid tumors are exceedingly rare,
      occurring at a relatively earlier age group with male preponderance, and
      invariably declare at a late clinical stage in our community. Histopathological
      features hallmark a locally advanced disease with an aggressive behavior.

PMID- 18327371
TI  - Quality improvement program in an emergency department.
AB  - OBJECTIVE: To describe the quality assurance/improvement program in our emergency
      department ED. METHODS: This program involved monthly data collection and
      analysis, data-driven process change, staff education in the core concepts of
      quality, and data reanalysis from the years 2003 to 2006 at the King Abdul-Aziz
      Hospital, Al-Ahsa, Kingdom of Saudi Arabia. Data captured during the program
      included census data, chart review, and focused clinical audits. Continuous
      quality improvement measures collected at the beginning of the program and
      quarterly included: 1) quality indicators (length of stay [LOS] and rates of left
      against medical advice [AMA] or left without being seen [LWBS]), 2) percentage of
      patients that stay > or =3 hours in ED, unscheduled returns within 48 hours,
      inter-hospital transfer data, sentinel events tracking rates, and 3) nature of
      patient complaints. RESULTS: During the study period, the program demonstrated
      improvement in all measured areas. Despite an increase in patient volume of 47%
      to 51,698 visits/year, the mean monthly LOS remained static, the unscheduled
      returned visits dropped by 50% (2% to 1%), and patients leaving AMA decreased
      from 1.5% to 1.2%, and LWBS decreased from 1.6% to 0.8%. The rate of complaints
      dropped by 5 fold (1.3 per 1000 patients to 0.25). CONCLUSION: Our program
      demonstrated improvement in all the measured parameters.

PMID- 18327372
TI  - Prevalence of symptoms and risk of sleep apnea in middle-aged Saudi males in
      primary care.
AB  - OBJECTIVE: The prevalence of obstructive sleep apnea OSA has not been assessed in
      Saudi Arabia. We aimed to assess the prevalence of individuals who were at risk
      of OSA in a sample of middle-aged Saudi males, using the Berlin questionnaire at
      primary care settings. METHODS: The study was conducted at King Khalid University
      and King Fahd National Guard primary health care clinics in Riyadh, Kingdom of
      Saudi Arabia between December 2005 and March 2006. Berlin Questionnaire was
      administered by trained medical students to consecutive Saudi male patients in
      the age group 30-65 years attending the primary health care clinics, after
      explaining the procedure of the study. Based on the data collected and defined
      criteria, patients were stratified into high risk and low risk according to
      responses. RESULTS: Five hundred and seventy-eight middle-aged Saudi males with a
      mean age of 45.02 +/- 9.3 year were surveyed in this study. Snoring was present
      in 52.3%, and breathing pauses more than once per week was noticed in 11.3%.
      Based on the Berlin questionnaire stratification for risk of OSA, 33.3% were
      considered as high risk patients for OSA. The occurrence of daytime tiredness
      >once/week was reported by 35.5%. The prevalence of snoring and risk for OSA is
      similar to that reported in the US. CONCLUSION: In primary care setting, one in 3
      middle-aged Saudi males is at risk for OSA.

PMID- 18327373
TI  - Patterns of breastfeeding practice during the first 6 months of life in Saudi
      Arabia.
AB  - OBJECTIVE: To assess the breastfeeding practices in the first 6 months of infants
      at King Abdulaziz Medical City (KAMC), Riyadh, Kingdom of Saudi Arabia. METHODS:
      A cross-sectional study was carried out at KAMC in 2005. Infants who attended the
      primary care centers and well-baby clinic of the hospital for the 6-month's
      vaccine were included. Mothers were interviewed to collect information on the
      mothers, infants, and their breastfeeding practice. World Health Organization
      definitions were used for classification of infant nutrition patterns. RESULTS:
      Five hundred seventy eight infants were included in this study. The breastfeeding
      initiation among the sample was 95%. Most mothers supplemented the infants with
      milk formula (83.4%) or fluids (94%) during the first 6 months. The percent of
      exclusive breastfeeding was 1.7% and the partial breastfeeding breast milk with
      formula was the most common type of feeding (78.8%). Lactation duration dropped
      to 50% at 6 months of age. Factors favoring the milk formula use were
      introduction of the formula in the first day of life and maternal reasons of
      inadequate milk. Lactation duration and formula introduction were found to be
      significantly associated with mothers' parity, working status, and combined
      contraceptive pill use. CONCLUSION: Prevalence of exclusive breastfeeding was
      extremely low in our population. Partial breastfeeding was the trend for feeding
      in the first 6 months of life, which was accompanied with rapid decline in
      lactation duration.

PMID- 18327374
TI  - Patient satisfaction with primary health care services in Riyadh.
AB  - OBJECTIVE: To assess the level of patients' satisfaction with primary health care
      PHC services in health centers affiliated to Riyadh Military Hospital RMH,
      Riyadh, Kingdom of Saudi Arabia. METHODS: A cross-sectional study was conducted
      in 3 PHC centers, affiliated to Riyadh Military Hospital RMH, Riyadh, Kingdom of
      Saudi Arabia, over 2 months period in 2006, data was collected using a self
      administered questionnaire to assess patients' overall satisfaction with PHC
      services and their level of satisfaction with 5 PHC domains: reception services,
      accessibility, continuity of care, communication, and enablement. RESULTS: Seven
      hundred questionnaires were distributed yielding 86.6% response rate, 39.6% of
      our patients were 20-30 years old, 51.5% of the respondents were females, 76.4%
      were married and 34.5% of them showed a medical visit frequency of a minimum of 8
      times per year. The domains of PHC with the highest level of reported
      satisfaction was enablement (70.6%). The poorest level of satisfaction was at the
      continuity of care (56.3%). The mean score of satisfaction with reception was
      70.0%, communication 69.2%, and accessibility to care was 62.4%. The overall
      satisfaction level was 64.2%. Patients of older age were more satisfied with PHC
      services than their younger counterparts (p-value<0.001) and patients with lower
      education level were more satisfied (p-value<0.001). Patients' satisfaction was
      inversely related to their average annual visit frequency to PHC centers (p-value
      =0.015). There was no relation found between patients' satisfaction and their
      gender, marital status, occupational status, and their average monthly income.
      CONCLUSION: The level of satisfaction with PHC services in health centers
      affiliated to RMH is relatively low, results identified areas in which quality
      improvement is required, mainly accessibility and continuity of care.

PMID- 18327375
TI  - The use of nasal stent for choanal atresia.
AB  - OBJECTIVE: To assess the role of the use of nasal stent (NS) on the outcome of
      choanal atresia (CA) surgeries, as well as the effect on the age at the time of
      surgery. METHODS: The study involved a retrospective review of the files of the
      case with the diagnosis of congenital CA that were surgically managed at King
      Abdul-Aziz University Hospital between January 1999 and June 2005. The review
      included: the age, gender, associated congenital anomalies, surgical
      intervention, and use of nasal stent (NS). A comparative study was carried out
      between the outcome of the cases who received NS, and those who did not. RESULTS:
      A total of 31 cases with the diagnosis of CA comprised our study group. Thirteen
      of the cases received NS and 18 did not. Generally, the use of NS for CA surgery
      resulted in poor outcome. Seventy-five percent of the unilateral cases with no-NS
      had successful outcome compared to 13% of those who received NS (p=0.00988). On
      the other hand, only 33% of the bilateral cases with no-NS had a successful
      outcome compared to 60% of those who received NS (p=0.3917). CONCLUSION: NS
      mandates an increased medical care. Its use in unilateral CA was associated with
      poor outcome. Based on our findings, it is recommended not to use NS in
      unilateral CA, as well as to postpone the surgical intervention, if possible,
      until the child is one year old or more.

PMID- 18327376
TI  - Presentations of agenesis of the hemidiaphragm in an adult.
AB  - A 67-year-old man presented with chest tightness and vomiting of one-week
      duration. On physical examination bowel sounds were heard on the left chest.
      Plain chest x-ray, barium swallow, and CT scan suggested gastric volvulus with
      diaphragmatic hernia. At laparotomy there was complete agenesis of the left
      hemidiaphragm with no diaphragmatic remnants seen and no associated lung
      hypoplasia. This is an extremely rare condition and careful assessment is needed
      to differentiate between diaphragmatic hernia and agenesis of the diaphragm as
      more cases could be diagnosed in the future as a result of good perinatal care of
      agenesis of hemidiaphragm AHD and long term survival to adulthood.

PMID- 18327377
TI  - Primitive neuroectodermal tumor of the ovary.
AB  - A 31-year-old woman presented to King Abdulaziz University Hospital complaining
      of an abdominal pain and a rapid increase in abdominal girth. An ultrasound and
      MRI, revealed a huge cystic ovarian mass without ascites. Ovarian tumor markers
      were all within normal range. Exploratory laparotomy showed huge right ovarian
      mass with omental mass. Frozen section from the omentum showed metastatic
      malignant neoplasm. Total abdominal hysterectomy was carried out with bilateral
      salpingooophorectomy and omentectomy with residual tumor of less then one
      centimeter. Final pathology assessment showed primitive neuroectodermal tumor
      arising from the right ovary. She received post- operative chemotherapy. Four
      months later she had recurrence and was given second line chemotherapy, but she
      did not respond and died 15 months after the diagnosis due to obstructive
      uropathy.

PMID- 18327378
TI  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis in 2 sisters.
AB  - Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a
      rare autosomal recessive tubular disorder characterized by excessive renal
      magnesium and calcium wasting, eventually, progressing to renal failure. It has
      been recently attributed to a mutation in the Claudin 16 (CLDN 16) gene of the
      Paracellin-1 (PCLN-1) tight junction protein. Herein, we report 2 sisters with
      FHHNC. Both sisters presented at an early stage with hypomagnesemia and
      hypocalcemia. The first patient was initially mislabeled and treated as a case of
      hypoparathyroidism, while the second patient was diagnosed retrospectively after
      the diagnosis of her sister. The 2 patients developed end stage renal disease.

PMID- 18327379
TI  - Munchausen syndrome by proxy and child's rights.
AB  - Munchausen syndrome by proxy (MSBP) is an extreme form of child abuse in which
      perpetrators induce life-threatening conditions in their children. A case of MSBP
      is described in detail. Difficulties in diagnosis and management in this part of
      the world are presented. Until now, no national legal guidelines exist in the
      Kingdom of Saudi Arabia (KSA) to child abuse in general and MSBP in particular.
      Urgent guidelines, policies, and legal system are required in the KSA.

PMID- 18327380
TI  - Laparoscopic enucleation of a duodenal lipoma, with review of the literature.
AB  - We present a case of duodenal lipoma in a 53-year-old lady causing symptoms of
      vomiting and abdominal discomfort, treated by laparoscopic enucleation. Lipomas
      of the duodenum are rare tumors with less than 230 cases reported in the
      literature, most of these are from autopsy records rather than clinical
      experience. Most recent reports are of endoscopic excision of these tumors while
      operative procedures, although less frequent, have been described for specific
      indications. We present a case of a duodenal lipoma excised laparoscopically with
      a review of the literature.

PMID- 18327381
TI  - Advanced breast cancer associated with atypical cells in accessory breast.

PMID- 18327382
TI  - Spinal anesthesia with minidose bupivacaine-fentanyl for cesarean section in
      preeclamptic parturients.

PMID- 18327383
TI  - Our experiences in surgical repair of secundum atrial septal defect in adults:
      early and mid-term results.

PMID- 18327384
TI  - Osteogenic activity of Sadat-Habdan mesenchymal stimulating peptide in diaphyseal
      segmental defects.

PMID- 18327385
TI  - Renal failure in patients with multiple myeloma: a single center experience.

PMID- 18327386
TI  - Pain status in Saudi governmental hospitals.

PMID- 18327387
TI  - Saudi newborn screening: a national public health program: needs, costs, and
      challenges.

PMID- 18327388
TI  - The effect of propolisis and mesalazine on bacterial translocation in an
      experimental colitis model.

PMID- 18327389
TI  - A renaissance for the contact system in blood coagulation?

PMID- 18327390
TI  - Perplexity of monocyte responses to C-reactive protein (CRP).

PMID- 18327391
TI  - A long-awaited small step forward in the management of the post-thrombotic
      syndrome.

PMID- 18327392
TI  - From molecules to medicine: new horizons in vascular biology and thrombosis (Part
      II).

PMID- 18327393
TI  - P2 receptors, platelet function and pharmacological implications.
AB  - ADP and ATP play a crucial role in platelet activation and their receptors are
      potential targets for antithrombotic drugs. The ATP-gated cation channel P2X(1)
      and the two G protein-coupled ADP receptors, P2Y(1) and P2Y(12), selectively
      contribute to platelet aggregation and formation of a thrombus. Owing to its
      central role in the growth and stabilization of a thrombus, the P2Y(12) receptor
      is an established target of antithrombotic drugs like the thienopyridines
      clopidogrel or prasugrel, or competitive antagonists such as cangrelor or
      AZD6140. The optimal inhibition of this receptor to reach clinical efficacy while
      preserving patients from unacceptable bleeding is a matter of debate. On the
      other hand, studies in P2Y(1) and P2X(1) knockout mice and using selective P2Y(1)
      and P2X(1) antagonists have shown that these receptors are also attractive
      targets for new antithrombotic compounds. Finally, the regulation by the P2
      receptors of the platelet involvement in inflammatory processes is also briefly
      discussed.

PMID- 18327394
TI  - Platelet GPIb complex as a target for anti-thrombotic drug development.
AB  - Specific inhibition of platelet function is a major target of anti-thrombotic
      drug research. Platelet receptors are both accessible and specific but have
      multiple functions often linked to a wide range of ligands. GPIb complex is best
      known as a major platelet receptor for von Willebrand factor essential for
      platelet adhesion under high shear conditions found in arteries and in
      thrombosis. Recent animal studies have supported inhibition of GPIb as a good
      candidate for anti-thrombotic drug development with several classes of proteins
      showing important specific effects and the required discrimination between roles
      in haemostasis and thrombosis is important to protect against bleeding
      complications. These include antibodies, several classes of snake venom proteins,
      mutant thrombin molecules and peptides affecting subunit interactions. However,
      due to the nature of its receptor-ligand interactions involving large protein
      protein interfaces, the possibility of developing classic pharmaceutical
      inhibitors for long term (and perhaps oral) treatment is still unclear, and
      additional information about structural interactions and signalling mechanisms is
      essential.

PMID- 18327395
TI  - Platelet-vessel wall interactions in atherosclerotic disease.
AB  - During the prolonged course of atherosclerotic disease, platelets are of central
      importance as they contribute to the initiation of the disease, to its
      progression and acute exacerbation but also provide potential regenerative
      mechanisms. Platelets secrete chemokines and cytokines that mediate vascular
      inflammation and are in turn activated by substances released from cells of the
      vascular wall. These interactions represent positive and negative feedback loops,
      which in case of dysregulation may lead to development and progression of
      disease. Furthermore, platelet adhesion to the endothelium is critical for the
      initiation of atherosclerotic lesion formation in vivo. Even prior to endothelial
      denudation, platelet adhesion governed by disturbed flow at predilection sites
      for atherosclerosis induces recruitment of proatherosclerotic cells and release
      of proinflammatory mediators from all involved cell types. Finally, the
      pathogenetic role of platelets for late atheroclerotic events including plaque
      rupture, microembolism or spasms within the microcirculation is well established.
      However, increasing evidence indicates that platelets mediate on the other hand
      potential regenerative mechanisms. Platelets recruit circulating progenitor cells
      to sites of vascular injury. Furthermore, they influence their biological
      activity and maturation. Therefore, platelets contribute at all stages of
      vascular disease by interfering with highly dynamic processes. Understanding
      interactions of platelets with other circulating cells and the vascular wall is a
      prerequisite to understand cardiovascular disease and to identify potential
      therapeutic targets.

PMID- 18327396
TI  - Individualized antithrombotic therapy in high risk patients after coronary
      stenting. A double-edged sword between thrombosis and bleeding.
AB  - Dual antiplatelet therapy with aspirin and clopidogrel is currently the standard
      therapy after coronary stent implantation to prevent a life-threatening stent
      thrombosis. However, a variety of procedural and individual factors contribute to
      the individual patient risk and have to be taken into account to allow for an
      individual recommendation for both the duration and intensity of the antiplatelet
      therapy. Obviously, the benefit of the prevention of stent thrombosis by
      antithrombotic therapy has to outweigh the risk of severe bleeding complications.
      Depending on the individual clinical situation and procedural characteristics
      (stent type, length, angiographic result etc.), the recommended duration of the
      combined antiplatelet therapy currently varies from four weeks to at least one
      year. These recommendations are mainly based on large, prospective, randomized
      trials and evidence-based guidelines. However, in a subgroup of high-risk
      patients there is insufficient evidence for the benefit of conventional dual
      antiplatelet regimen. These include i) patients with an indication for
      anticoagulation, ii) patients with urgent need for an operation requiring a
      perioperative withholding of antiplatelet therapy, as well as iii) clopidogrel
      low responders. This review aims to provide a stratification to define patient
      collectives who may benefit from more individualized antithrombotic regimens on
      behalf of currently available literature and guidelines.

PMID- 18327397
TI  - Current view on alveolar coagulation and fibrinolysis in acute inflammatory and
      chronic interstitial lung diseases.
AB  - Acute inflammatory and chronic interstitial lung diseases are characterized by
      excessive and persistent fibrin deposition in the lung. Intraalveolar fibrin
      accumulation, observed under these conditions, arises from a leakage of plasma
      proteins (including fibrinogen) into the alveolar space in combination with a
      disbalance of alveolar haemostasis. Tissue factor in association with factor VIIa
      and inhibition of urokinase by plasminogen activator inhibitor-1 are major
      factors that are responsible for the procoagulant and antifibrinolytic state. In
      addition, in acute respiratory distress syndrome (ARDS) patients, factor VII
      activating protease and extracellular RNA, which may be released into the
      extracellular milieu from damaged cells during lung injury, may contribute to
      fibrin formation as well. Fibrin itself can increase vascular permeability,
      influence the expression of inflammatory mediators and alter the migration and
      proliferation of various cell types. Additionally, fibrin may inactivate
      pulmonary surfactant and provide a matrix on which fibroblasts can migrate and
      produce collagen. Furthermore, cellular activities of haemostatic proteases may
      also contribute to proinflammatory and fibrotic processes in the lung. The
      application of coagulation inhibitors, like tissue factor pathway inhibitor,
      active site-inactivated factor VIIa, activated protein C, antithrombin, heparin
      or hirudin turned out to be beneficial in experimental models of acute and
      chronic lung injury. However, the ability of anticoagulant and profibrinolytic
      agents to improve clinical outcome remains to be elucidated. In the current
      article, the role of the alveolar coagulation and fibrinolysis systems in acute
      inflammatory and chronic interstitial lung diseases is discussed with regard to
      pathomechanisms and modalities of intervention.

PMID- 18327398
TI  - Treatment of pulmonary embolism: The use of low-molecular-weight heparin in the
      inpatient and outpatient settings.
AB  - Pulmonary embolism (PE) remains a major clinical problem associated with
      considerable mortality and morbidity. In patients with PE, appropriate
      anticoagulant therapy has been shown to significantly reduce both recurrence and
      mortality. Low-molecular-weight heparin (LMWH) is at least as effective as
      unfractionated heparin (UFH) in the treatment of PE, with a similar risk of
      bleeding. Furthermore, LMWH offers more predictable pharmacokinetics and
      anticoagulant effects. As a result, current guidelines from both the American
      College of Chest Physicians and the joint American College of Physicians/American
      Academy of Family Physicians recommend the use of LMWH over UFH (in patients with
      submassive PE). Outpatient treatment with LMWH has been shown to be feasible in
      many patients, and offers the potential for cost-savings and improvements in
      health-related quality of life. Further data are needed to support an evidence
      based recommendation for the use of LMWH in the outpatient treatment of PE.

PMID- 18327399
TI  - The interaction of fragment 1 of prothrombin with the membrane surface is a
      prerequisite for optimum expression of factor Va cofactor activity within
      prothrombinase.
AB  - Incorporation of factor (F) Va into prothrombinase directs prothrombin activation
      by FXa through the meizothrombin pathway, characterized by initial cleavage at
      Arg(320). We have shown that a pentapeptide with the sequence DYDYQ specifically
      inhibits this pathway. It has been also established that Hir(54-65)(SO(3)(-)) is
      a specific inhibitor of prothrombinase. To understand the role of FVa within
      prothrombinase at the molecular level, we have studied thrombin formation by
      prothrombinase in the presence of various prothrombin-derived fragments alone or
      in combination. Activation of prethrombin 1 is slow with cleavages at Arg(320)
      and Arg(271) occurring with similar rates. Addition of purified fragment 1 to
      prethrombin 1 accelerates both the rate of cleavage at Arg(320) and thrombin
      formation. Both reactions were inhibited by Hir(54-65)(SO(3)(-)) while DYDYQ had
      no significant inhibitory effect on prethrombin 1 cleavage in the absence or
      presence of fragment 1. Similarly, activation of prethrombin 2 by prothrombinase,
      is inhibited by Hir(54-65)(SO(3)(-)), but is not affected by DYDYQ. Addition of
      purified fragment 1*2 to prethrombin 2 accelerates the rate of cleavage at
      Arg(320) by prothrombinase. This addition also results in a significant
      inhibition of thrombin formation by DYDYQ and is concurrent with the elimination
      of the inhibitory effect of Hir(54-65)(SO(3)(-)) on the same reaction. Finally, a
      membrane-bound ternary complex composed of prethrombin 2/fragment 1*2/Hir(54
      65)(SO(3)(-)) is inhibited by DYDYQ. Altogether, the data demonstrate that
      membrane-bound fragment 1 is required to promote optimum Fva cofactor activity
      which in turn is translated by efficient initial cleavage of prothrombin by
      prothrombinase at Arg(320).

PMID- 18327400
TI  - Molecular characterization of two novel mutations causing factor XI deficiency: A
      splicing defect and a missense mutation responsible for a CRM+ defect.
AB  - Severe factor XI (FXI) deficiency is a bleeding disorder generally inherited as
      an autosomal recessive trait and characterized by haemorrhagic symptoms mainly
      associated with injury or surgery. So far, more than 150 causative molecular
      defects have been identified throughout the F11 gene. In the present study, we
      investigated the molecular basis of FXI deficiency in two Italian patients.
      Mutational screening of the F11 gene disclosed a novel missense substitution
      (Arg184Gly) in exon 7 and two splicing mutations: a novel G>A transition
      affecting the last nucleotide of exon 4 (325G>A), and the already known
      IVS6+3A>G. RT-PCR assays were performed on total RNA extracted from platelets and
      lymphocytes of each patient. Sequencing of RT-PCR products demonstrated that both
      325G>A and IVS6+3A>G mutations abolish the corresponding donor splice site,
      causing the skipping of the affected exon; this in turn results in a frameshift
      introducing a premature termination codon. Expression of recombinant FXI
      Arg184Gly revealed a 70% reduction in FXI activity, suggesting that the Arg184Gly
      mutation might cause a cross-reactive material positive (CRM+) deficiency. In
      conclusion, the functional consequences of two splicing mutations leading to FXI
      deficiency have been elucidated. Moreover, we report a novel missense mutation in
      the FIX-binding region of the FXI A3 domain leading to a CRM+ deficiency.

PMID- 18327401
TI  - An algal sulfated galactan has an unusual dual effect on venous thrombosis due to
      activation of factor XII and inhibition of the coagulation proteases.
AB  - Sulfated galactan from the red alga Botryocladia occidentalis has a potent
      anticoagulant activity, due to its ability to enhance thrombin and factor Xa
      inhibition by antithrombin and/or heparin cofactor II. It is less active than
      unfractionated heparin in arterial thrombosis, but in a venous thrombosis
      presents a dual effect, inhibiting thrombosis in low but not in high doses. This
      dual effect on venous thrombosis is a consequence of two actions, one that
      inhibits thrombin and factor Xa and one that induces factor XII activation. In
      order to dissociate these effects, we prepared derivatives of the sulfated
      galactan with low molecular weights. Two fractions that were similar in size to
      unfractionated heparin and low-molecular-weight heparin were obtained. As the
      molecular weight decreased, the ability to activate factor XII and to promote
      inhibition of coagulation proteases in the presence of antithrombin and heparin
      cofactor II diminished. At approximately 5 kDa, the sulfated galactan fragment
      had no effect on factor XII activation, and showed the same effect as
      unfractionated heparin in a venous thrombosis model. The approximately 5-kDa
      fragment is an antithrombotic with several advantages: i) It is as active as
      unfractionated heparin in venous thrombosis, but it has little activity in
      arterial thrombosis; ii) It inhibits venous thrombosis with very little
      anticoagulant effect; iii) It does not cause bleeding; and iv) It is not obtained
      from mammals.

PMID- 18327402
TI  - Slight differences in sulfation of algal galactans account for differences in
      their anticoagulant and venous antithrombotic activities.
AB  - We compared sulfated galactans (SGs) from two species of red algae using specific
      coagulation assays and experimental models of thrombosis. These polysaccharides
      have an identical saccharide structure and the same size chain, but with slight
      differences in their sulfation patterns. As a consequence of these differences,
      the two SGs differ in their anticoagulant and venous antithrombotic activities.
      SG from G. crinale exhibits procoagulant and prothrombotic effects in low doses
      (up to 1.0 mg/kg body weight), but in high doses (>1.0 mg/kg) this polysaccharide
      inhibits both venous and arterial thrombosis in rats and prolongs ex-vivo
      recalcification time. In contrast, SG from B. occidentalis is a very potent
      anticoagulant and antithrombotic compound in low doses (up to 0.5 mg/kg body
      weight), inhibiting venous experimental thrombosis and prolonging ex-vivo
      recalcification time, but these effects are reverted in high doses. Only at high
      doses (>1.0 mg/kg) the SG from B. occidentalis inhibits arterial thrombosis. As
      with heparin, SG from G. crinale does not activate factor XII, while the
      polysaccharide from B. occidentalis activates factor XII in high concentrations,
      which could account for its procoagulant effect at high doses on rats. Both SGs
      do not modify bleeding time in rats. These results indicate that slight
      differences in the proportions and/or distribution of sulfated residues along the
      galactan chain may be critical for the interaction between proteases, inhibitors
      and activators of the coagulation system, resulting in a distinct pattern in anti
      and procoagulant activities and in the antithrombotic action.

PMID- 18327404
TI  - Effect of an anti-sulfatide single-chain antibody probe on platelet function.
AB  - Sulfatide (galactocylceramide-3'-sulfate), a cell surface glycosphingolipid
      interacts with several cell adhesion molecules including fibrinogen, von
      Willebrand factor (VWF), P-selectin, thrombospondin (TSP) and laminin, which are
      involved in haemostasis. We have used a sulfatide-specific single-chain fragment
      variable (scFv) antibody probe PA38 and sulfatide-deficient mice to investigate
      the role of membrane sulfatide in platelet function. PA38 bound to platelets and
      binding increased following platelet activation. Sulfatide was localized as a
      large cluster towards the center of the platelet surface when examined in a
      confocal microscope. PA38 (20 microg/ml) inhibited the adhesion of activated
      platelets to fibrinogen, VWF, P-selectin, TSP1 and laminin by 30%, 30%, 75%, 20%
      and 35%, respectively, compared to a control scFv (p < 0.05). Furthermore, PA38
      inhibited collagen, ADP, thrombin and ristocetin-induced platelet aggregation in
      PRP by 25%, 30%, 18% and 20%, respectively, compared to the control scFv (p <
      0.05). In a PFA-100 platelet function assay, PA38 prolonged the occlusion time by
      25% (p < 0.05). Under flow PA38 decreased the thrombus formation on collagen by
      31%, (p < 0.01). Sulfatide-deficient mice displayed an extended lag-phase in
      collagen-induced platelet aggregation compared to wild type (p < 0.05), though in
      vivo haemostasis did not differ significantly. Thus, this study provides new
      evidence for a role for membrane sulfatide in platelet function.

PMID- 18327403
TI  - Clinical presentation and time-course of postoperative venous thromboembolism:
      Results from the RIETE Registry.
AB  - There is little literature about the clinical presentation and time-course of
      postoperative venous thromboembolism (VTE) in different surgical procedures.
      RIETE is an ongoing, prospective registry of consecutive patients with
      objectively confirmed, symptomatic acute VTE. In this analysis, we analysed the
      baseline characteristics, thromboprophylaxis and therapeutic patterns, time
      course, and three-month outcome of all patients with postoperative VTE. As of
      January 2006, there were 1,602 patients with postoperative VTE in RIETE: 393
      (25%) after major orthopaedic surgery (145 elective hip arthroplasty, 126 knee
      arthroplasty, 122 hip fracture); 207 (13%) after cancer surgery; 1,002 (63%)
      after other procedures. The percentage of patients presenting with clinically
      overt pulmonary embolism (PE) (48%, 48%, and 50% respectively), the average time
      elapsed from surgery to VTE (22 +/- 16, 24 +/- 16, and 21 +/- 15 days,
      respectively), and the three-month incidence of fatal PE (1.3%, 1.4%, and 0.8%,
      respectively), fatal bleeding (0.8%, 1.0%, and 0.2%, respectively), or major
      bleeding (2.3%, 2.9%, and 2.8%, respectively) were similar in the three groups.
      However, the percentage of patients who had received thromboprophylaxis (96%, 76%
      and 52%, respectively), the duration of prophylaxis (17 +/- 9.6, 13 +/- 8.9, and
      12 +/- 11 days, respectively) and the mean daily doses of low-molecular-weight
      heparin (4,252 +/- 1,016, 3,260 +/- 1,141, and 3,769 +/- 1,650 IU, respectively),
      were significantly lower in those undergoing cancer surgery or other procedures.
      In conclusion, the clinical presentation, time-course, and three-month outcome of
      VTE was similar among the different subgroups of patients, but the use of
      prophylaxis in patients undergoing cancer surgery or other procedures was
      suboptimal.

PMID- 18327405
TI  - C-reactive protein induces pro- and anti-inflammatory effects, including
      activation of the liver X receptor alpha, on human monocytes.
AB  - Non-specific markers of inflammation such as C-reactive protein (CRP) are
      associated statistically with an increased risk of atherosclerosis through
      mechanisms that have not yet been fully elucidated. We investigated the effects
      of CRP on several aspects of human monocyte biology, a cell type involved in the
      initiation and progression of atherosclerosis. Blood monocytes isolated from
      healthy men and premenopausal women (n = 9/group) were exposed to purified CRP
      (25 microg/ml) for 12 hours. Changes in gene expression were analyzed using a
      custom-made array containing oligonucleotide sequences of 250 genes expressed by
      activated monocytes and confirmed by quantitative PCR. CRP increased
      significantly the expression of the cytokines interleukin (IL)-1alpha, IL-1beta
      and IL-6, and the chemokines GRO-alpha, GRO-beta and IL-8. CRP also displayed
      anti-inflammatory effects through upregulation of liver X receptor (LXR) alpha
      and activin receptor expression, and down-regulation of alpha 2-macroglobulin
      expression. Increased LXRalpha mRNA expression in both monocytes and the
      monocytic cell lineTHP-1 was associated with increased LXRalpha protein
      expression and nuclear translocation, as well as increased ABCA1 mRNA expression,
      a target gene of LXRalpha. Western blot analysis revealed CRP-induced nuclear
      translocation of NF-kappaB and activation of p42/44, MAP and Akt kinases. CRP
      induced LXRalpha mRNA expression was inhibited by anti-CD64 (FcgammaRI)
      antibodies and by p42/44 and PI3 kinase inhibitors. This hypothesis-generating
      study demonstrates that CRP modulates the expression of genes that contribute to
      both pro- and anti-inflammatory responses in human monocytes. Among these novel
      anti-inflammatory effects, we show clearly that CRP activates the LXRalpha
      pathway.

PMID- 18327406
TI  - Concentration-dependent roles for heparin in modifying lipopolysaccharide-induced
      activation of mononuclear cells in whole blood.
AB  - In addition to their anticoagulant activity, unfractionated heparin (UFH) and low
      molecular-weight heparin (LMWH) have important immunomodulatory properties.
      However, different studies have reported conflicting pro- and anti-inflammatory
      effects in association with heparin. Moreover, the molecular basis for these
      heparin effects on inflammation remains unclear. It was the objective of this
      study to determine how UFH and LMWH regulate lipopolysaccharide (LPS)-induced
      activation of human mononuclear cells in whole blood, and define the role of
      lipopolysaccharide-binding protein (LBP) in mediating this effect. Whole blood
      was pre-treated with UFH or LMWH (0.1-200 IU/ml), prior to stimulation with LPS
      (10 ng/ml). After six hours, monocyte pro-inflammatory cytokine (interleukin (IL)
      1beta, IL-6, IL-8, and TNF-alpha) secretion was determined by plasma ELISA.
      Parallel experiments using THP-1 cell line and primary monocytes were performed
      under serum-free conditions, in the presence or absence of LBP (50-100 nM). Under
      serum-free conditions, heparin demonstrated dose-dependent anti-inflammatory
      effects, significantly reducing secretion of pro-inflammatory cytokines (IL
      1beta, IL-6, IL-8, and TNF-alpha) in response to LPS-stimulation of THP-1 cells
      and primary monocytes. In contrast, in the presence of LBP, both UFH and LMWH
      demonstrated dose-dependent pro-inflammatory effects at all heparin
      concentrations. In ex-vivo whole blood experiments, pro-inflammatory effects
      (increased IL-1beta and IL-8 following LPS-stimulation) of heparin were also
      observed, but only at supra-therapeutic doses (10-200 IU/ml). Our data
      demonstrate that in the absence of LBP, the direct effect of heparin on LPS
      stimulated monocytes is anti-inflammatory. However in whole blood, the
      immunomodulatory effects of heparin are significantly more complex, with either
      pro- or anti-inflammatory effects dependent upon heparin concentration.

PMID- 18327407
TI  - Tissue factor pathway inhibitor (TFPI) interferes with endothelial cell migration
      by inhibition of both the Erk pathway and focal adhesion proteins.
AB  - Tissue factor pathway inhibitor (TFPI) is a plasma Kunitz-type serine protease
      inhibitor that is mainly known for its inhibition of tissue factor-mediated
      coagulation. In addition to its anticoagulant properties, emerging data show that
      TFPI may also regulate endothelial cell functions via a non-haemostatic pathway.
      In this work we demonstrate that at concentrations within the physiological
      range, TFPI inhibits both endothelial cell migration and their differentiation
      into capillary-like structures in vitro. These effects were specific to
      endothelial cells since no inhibitory effect was observed on the migration of
      tumor (glioblastoma) cells. Inhibition of endothelial cell migration was
      correlated with a concomitant loss in cell adhesion, suggesting an alteration of
      focal adhesion complex integrity. Accordingly, we observed that TFPI inhibited
      the phosphorylation of focal adhesion kinase and paxillin, two key proteins
      involved in the scaffolding of these complexes, and that this effect was specific
      to endothelial cells. These results suggest that TFPI influences the angiogenic
      process via a non-haemostatic pathway, by downregulating the migratory mechanisms
      of endothelial cells.

PMID- 18327408
TI  - Magnesium maintains endothelial integrity, up-regulates proteolysis of ultra
      large von Willebrand factor, and reduces platelet aggregation under flow
      conditions.
AB  - Mg (++) regulates endothelial functions and has anti-inflammatory effects. Its
      effects on thrombosis have been demonstrated, but the mechanism remains poorly
      understood. We investigated the roles of MgSO(4) in regulating the release and
      cleavage of the prothrombotic ultra-large (UL) von Willebrand factor (VWF) and
      VWF-mediated platelet adhesion and aggregation. Washed platelets were perfused
      over cultured endothelial cells from human umbilical cord veins under a shear
      stress of 2.5 dyn/cm(2). Release and cleavage of ULVWF by ADAMTS-13 was measured
      in the absence or presence of physiological or therapeutic levels of MgSO(4).
      Whole blood or plasma-free reconstituted blood was perfused over immobilized
      collagen to measure the effect of MgSO(4) on platelet adhesion and aggregation.
      Also studied were the effects of MgSO(4) on ristocetin-induced platelet
      aggregation andVWF-collagen interaction. Maintenance of endothelial integrity
      required physiological levels of MgSO(4), but exogenous MgSO(4) showed no
      additional benefits. Exogenous MgSO(4) significantly enhanced the cleavage of the
      newly released ULVWF strings by ADAMTS-13 and markedly reduced platelet
      aggregation on immobilized collagen under flow conditions. This effect is likely
      to be mediated through VWF as Mg(++) partially inhibited ristocetin-induced
      platelet aggregation and VWF binding to collagen. MgSO(4) is critical for
      maintaining endothelial integrity and regulates ULVWF proteolysis and aggregation
      under flow conditions. These results provide a new insight into additional
      mechanisms involved with magnesium therapy.

PMID- 18327409
TI  - The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular
      risk. Two case-control studies and a meta-analysis.
AB  - NAD(P)H oxidase is a prominent source of reactive oxygen species in the
      vasculature. Vascular NAD(P)H oxidase is comprised of several subunits, one of
      which, p22phox, is encoded by a gene exhibiting several allelic variants. Here
      the C(242)T nucleotide transition has been found to alter superoxide anion
      production and associated with an altered risk of coronary artery disease (CAD).
      We assessed the role of this variant in two case-control studies, and performed a
      meta-analysis of previously reported investigations relating it to vascular risk.
      Population I was comprised of 492 subjects with type 2 diabetes, with or without
      macrovascular disease, matched for age, sex, and duration of diabetes. Population
      II was comprised of 158 subjects with or without either CAD or cerebro-vascular
      disease, and matched for age, sex, smoking status, weight category and the
      presence of hypertension, dyslipidemia, and diabetes. Our findings were meta
      analyzed together with additional studies retrieved from the literature. The
      C(242)T polymorphism distribution did not differ between cases and controls in
      populations I and II both at univariate and multivariate analyses, and this was
      confirmed in a meta-analysis with 11 previously published populations. The meta
      analysis, however, suggested a protective role of the T allele on CAD as an end
      point in Asian populations. In conclusion, these data suggest a significant
      heterogeneity for a modulating role of the T allele in the C(242)T polymorphism
      of p22-phox for the occurrence of CAD across ethnicities, with the absence of a
      significant effect in Caucasians.

PMID- 18327410
TI  - Increased thrombin generation in persons with echogenic carotid plaques.
AB  - Echolucent carotid plaques are associated with higher risk for future ischemic
      cerebrovascular events (CVE) than echogenic plaques independent of the degree of
      stenosis. Elevated markers of thrombin generation are associated with
      atherosclerotic plaques and are increased in the acute and chronic phases of CVE.
      The present study was conducted to investigate the influence of plaque morphology
      on thrombin generation in persons with carotid stenosis. One hundred twenty-eight
      persons with carotid stenosis (>or=35% lumen diameter reduction) and 136 matched
      controls without stenosis were recruited from the health survey of the Tromso
      Study. Blood samples were collected and plaque morphology determined by
      ultrasonography. Thrombin generation was assessed by thrombin-antithrombin
      complexes (TAT) and by prothrombin fragment 1+2 (F1+2). Persons with echogenic
      plaques (n = 63) had significantly higher levels of TAT (5.24 microg/l, 4.33
      6.14) (mean, 95%CI) than persons with echolucent plaques (n = 65) (3.44 microg/l,
      2.91-3.96, p < 0.001) and controls (n = 136) (3.33 microg/l, 3.06-3.60, p <
      0.001). They also had significantly higher levels of F1+2 (2.14 nM, 1.83-2.45)
      than persons with echolucent plaques (1.54 nM, 1.38-1.71, p < 0.001) and controls
      (1.49 nM, 1.40-1.58, p < 0.001). TAT and F1+2 increased linearly with plaque
      echogenicity (p = 0.002 and p = 0.001, respectively) independent of the degree of
      stenosis. Increased thrombin generation was associated with a significant
      increase in plasma factor V levels among persons with echogenic plaques compared
      to echolucent plaques (p = 0.049) and controls (p = 0.025). The present findings
      indicate that increasing plaque echogenicity, rather than plaque echolucency and
      the degree of stenosis, is associated with thrombin generation in persons with
      carotid stenosis.

PMID- 18327411
TI  - Selective inhibition of the platelet phosphoinositide 3-kinase p110beta as
      promising new strategy for platelet protection during extracorporeal circulation.
AB  - Extracorporeal circulation (ECC) is used in cardiac surgery for cardiopulmonary
      bypass as well as in ventricular assist devices and for extracorporeal membrane
      oxygenation. Blood contact with the artificial surface and shear stress of ECC
      activates platelets and leukocytes resulting in a coagulopathy and
      proinflammatory events. Blockers of the platelet glycoprotein (GP) IIb/IIIa
      (CD41/CD61) can protect platelet function during ECC, a phenomenon called
      "platelet anaesthesia", but may be involved in post-ECC bleeding. We hypothesized
      that the new selective phosphoinositide 3-kinase p110beta inhibitor TGX-221 that
      inhibits shear-induced platelet activation without prolonging the bleeding time
      in vivo may also protect platelet function during ECC. Heparinized blood of
      healthy volunteers (n = 6) was treated in vitro with either the GP IIb/IIIa
      blocker tirofiban, TGX-221 or as control and circulated in an ECC model. Before
      and after 30 minutes circulation CD41 expression on the ECC-tubing as measure for
      platelet-ECC binding and generation of the platelet activation marker beta
      thromboglobulin were determined using ELISA. Platelet aggregation and platelet
      granulocyte binding were analysed in flow cytometry. After log-transforming the
      data statistical evaluation was performed using multifactor ANOVA in combination
      with Tukey's HSD test (global alpha = 5%). Tirofiban and TGX-221 inhibited
      platelet-ECC interaction, platelet aggregation and platelet-granulocyte binding.
      Tirofiban also inhibited ECC-induced beta-thromboglobulin release. The observed
      inhibition of platelet-ECC interaction and platelet activation by tirofiban
      contributes to explain the mechanism of "platelet anaesthesia". TGX-221
      represents a promising alternative to GP IIb/IIIa blockade and should be further
      investigated for use during ECC in vivo.

PMID- 18327412
TI  - Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study
      of prophylactic intravenous administration in high risk situations.
AB  - During surgery and childbirth, patients with hereditary antithrombin (AT)
      deficiency are at high risk for thrombosis, and heparin prophylaxis may not be
      sufficiently efficacious. In these patients, exogenous AT may be used in
      association with heparin. A recombinant human AT (generic name: antithrombin
      alfa) has been developed. This multi-center study assessed the efficacy and
      safety of prophylactic intravenous administration of antithrombin alfa to
      hereditary AT deficient patients in high risk situations, including elective
      surgery, childbirth, or cesarean section. Antithrombin alfa was administered
      prior to and during the high risk period for restoration and maintenance of AT
      activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin
      K antagonists were used according to standard of care. The primary efficacy
      endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up
      to day 30 post dosing as assessed by independent central review of duplex
      ultrasonograms and/or venograms. Safety was assessed based on adverse events
      (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary
      AT deficiency patients received antithrombin alfa for a mean period of seven
      days. No clinically overt DVT occurred. Central review of ultrasonograms
      identified signs of acute DVT in two out of 13 evaluable patients. No
      antithrombin alfa-related AEs were reported. No patient developed anti
      antithrombin alfa antibodies. In conclusion, this study suggests that
      antithrombin alfa is a safe and effective alternative to human plasma-derived AT
      for treating hereditary AT deficiency patients at high risk for thromboembolic
      events.

PMID- 18327413
TI  - Evaluation of a venous-return assist device to treat severe post-thrombotic
      syndrome (VENOPTS). A randomized controlled trial.
AB  - Severe post-thrombotic syndrome (PTS) is responsible for considerable disability,
      reduced quality of life and increased health care costs. Current therapies are
      limited and often ineffective. We performed a two-centre, randomized, cross-over
      controlled trial to evaluate Venowave, a novel lower-limb venous-return assist
      device, for the treatment of severe PTS. Eligible subjects were allocated to
      receive, in randomized order, Venowave for eight weeks and a control device for
      eight weeks. The eight-week treatment periods were separated by a four-week
      period when no device was used (i.e. wash-out period). The primary outcome
      measure was a 'clinical success' defined as: i) reported benefit from the device;
      and ii) moderate or greater improvement in symptoms of PTS; and iii) willingness
      to continue using the device. Secondary outcome measures included quality of life
      (QOL) as measured by VEINES-QOL questionnaire (higher scores indicate better
      QOL), and PTS severity as measured by the Villalta PTS scale (higher scores
      indicate more severe PTS). The study was registered with Clinical Trials. gov
      (NCT00182208). Thirty-two patients were enrolled. Of these, 26 (80%) were also
      using graduated compression stockings. Twenty-six participants completed both
      trial periods. Clinical success occurred in 10 (31%) participants receiving
      Venowave and four (13%) participants receiving the control device, with two (6%)
      participants reporting a clinical success with both devices (P = 0.11). Mean
      VEINES-QOL score at the end of study period was significantly greater (P = 0.004)
      for Venowave (52.5; SD 5.8) compared to control (50.2; SD 6.2). Mean Villalta
      scale score at the end of study period was significantly decreased (P = 0.004)
      for Venowave (12.2; SD 6.3) compared to control (15.0; SD 6.1). In conclusion,
      Venowave appears to be a very promising new therapy for patients with severe PTS,
      which may be used alone or in combination with graduated compression stockings.

PMID- 18327414
TI  - von Willebrand disease, type 2B: A diagnosis more elusive than previously
      thought.

PMID- 18327416
TI  - The B-cell epitope of the monoclonal anti-factor VIII antibody ESH8 characterized
      by peptide array analysis.

PMID- 18327417
TI  - Effects of diabetes mellitus on platelet reactivity after dual antiplatelet
      therapy with aspirin and clopidogrel.

PMID- 18327418
TI  - Venous thrombosis in oral contraceptive users and the presence of the JAK2 V617F
      mutation.

PMID- 18327419
TI  - Temporal trends in mortality rates from visceral vein thrombosis in paroxysmal
      nocturnal haemoglobinuria: An optimistic view.

PMID- 18327420
TI  - Epidemiology of hepatitis C virus infection in Pakistan.
AB  - Since the discovery of hepatitis C virus (HCV) in 1989 as the causative agent of
      post-transfusion non-A non-B hepatitis, the epidemiology, pattern of
      transmission, different genotypes and clinical consequences of the disease have
      been studied worldwide, but little is known about the epidemiology of HCV
      infection in Pakistan. This paper reviews the available evidence on the
      epidemiology of HCV infection in Pakistan obtained via MEDLINE search (1970-2005)
      of published articles with key words hepatitis C and Pakistan, and other sources
      including ongoing discussions within the medical community. Approximately 10
      million people have been infected with HCV in Pakistan. The majority of patients
      have acquired their infection through unsafe injections, reuse of syringes and
      needles and community barber shops used for face and armpit shaving. More than
      two-thirds of HCV patients were 40 to 50 years old. Although at present a small
      proportion of those with chronic HCV infection develop liver failure or
      hepatocellular carcinoma, it is estimated that the incidence of these advanced
      disease complications will increase over the coming years.

PMID- 18327421
TI  - GrlA of enterohemorrhagic Escherichia coli O157:H7 activates LEE1 by binding to
      the promoter region.
AB  - BACKGROUND AND PURPOSE: The locus of enterocyte effacement (LEE) of
      enterohemorrhagic Escherichia coli (EHEC) O157:H7 encodes virulence factors that
      lead cooperatively to an attaching and effacing lesion on host large intestine
      cells. Global regulator of LEE activator (GrlA), encoded by the open reading
      frame 3 in the EHEC LEE, is known to serve as a positive regulator of LEE
      expression. However, how it functions to orchestrate gene expression remains
      unclear. METHODS: A grlA-deleted mutant strain was created, and the determinants
      needed for the LEE activation were addressed by complementation experiments. A
      DNA electrophoresis mobility-shifting assay was used to test a hypothesis that
      the activation occurs via a direct binding on the putative promoter region.
      RESULTS: Activation of the major LEE operons could be rescued by an over
      expression of LEE-encoded regulator (Ler), except for the LEE1 operon, expression
      of which absolutely required GrlA. Consistent with the latter observation, GrlA
      bound specifically to the putative LEE1 promoter region. Furthermore,
      determinants critical for this activity have been mapped to the N-terminal region
      of GrlA. CONCLUSION: GrlA upregulates the expression of LEE through binding of
      the LEE1 promoter, which in turn increases the level of Ler allowing it to
      function as a downstream activator. The opposing effect of global regulator of
      LEE repressor (GrlR) is explainable by in vitro findings that GrlR interacts with
      GrlA, suppressing the specific binding of GrlA on the LEE1 promoter.

PMID- 18327422
TI  - Synergistic action of vitamin D and retinoic acid restricts invasion of
      macrophages by pathogenic mycobacteria.
AB  - BACKGROUND AND PURPOSE: Phagosomal maturation arrest is known to play a central
      role in the survival of pathogenic mycobacteria within macrophages. The
      maturation arrest of mycobacterial phagosome results from the retention of
      tryptophan-aspartate-containing coat protein (TACO) on this organelle, enabling
      successful replication of the pathogen. We have shown earlier that vitamin D(3)
      and retinoic acid (RA) down-regulate TACO gene transcription in a dose-dependent
      manner. METHODS: In this study, we analyzed the promoter region of TACO gene
      using bioinformatics tools and observed that the vitamin D receptor
      (VDR)/retinoid-X-receptor (RXR) response sequence was highly functional. We also
      evaluated the effect of treatment with vitamin D(3)/RA on Mycobacterium
      tuberculosis entry and survival in cultured human macrophages. RESULTS: TACO gene
      down-regulation observed with vitamin D(3)/RA treatment occurred through
      modulation of this gene via the VDR/RXR response sequence present in the promoter
      region of TACO gene. Treatment of macrophages with vitamin D(3)/RA allows
      maturation of mycobacterial phagosome, leading to degradation of the pathogen.
      CONCLUSIONS: Our results elucidate the mechanism of TACO gene down-regulation
      observed with vitamin D(3)/RA. Furthermore, the results revealed that vitamin
      D(3)/RA treatment inhibits mycobacterial entry as well as survival within
      macrophages, possibly through rescue of phagosome maturation arrest. The
      developing knowledge in this area suggests that vitamin D(3)/RA may be of
      importance in the treatment of intracellular infection, particularly
      tuberculosis.

PMID- 18327423
TI  - The air pollutant sodium sulfite enhances mite crude extract-stimulated
      detachment of A549 airway epithelium cells.
AB  - BACKGROUND AND PURPOSE: It has been previously reported that the pollutant sodium
      sulfite (Na2SO3) can activate airway epithelial cells; however, there is as yet
      no evidence of any direct relationship between house dust mite allergen exposure
      and Na2SO3 with regards to the pathogenesis of airway allergy. This study
      investigated the effect of sulfite on mite-stimulated human airway epithelial
      cells. METHODS: The A549 human lung epithelial cell line was used as an in vitro
      model. Cells were treated with 10 microg/mL mite crude extract for 8 h and/or
      Na2SO3 (0, 10, 100, 500, 1000 and 5000 microM) for 16 h, and cell adhesion and
      dissociation on a cell culture plastic surface were quantitated with a 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Changes
      in cell adhesion were also analyzed by monitoring the expression of the cell
      surface of adhesion molecules integrin alpha2 (CD49b) and integrin alpha6 (CD49f)
      using flow cytometry. RESULTS: A549 cells treated with either mite crude extract
      only or Na2SO3 only did not show a significant increase in dissociation from the
      cell culture plastic surface. However, when cells were pretreated with mite
      extract for 8 h, followed by 16-h incubation with various concentrations of
      Na2SO3, cell dissociation was enhanced in a dose-dependent manner. A dose
      dependent decrease of CD49b and CD49f expression was also seen in cells treated
      with Na2SO3 only and in mite-pretreated cells. Mite treatment decreased CD49b
      expression, and a cumulative effect was seen in cells further treated with
      Na2SO3. CONCLUSION: Significant dissociation of airway epithelial cells with
      Na2SO3 stimulation only occurred in cells pretreated with mite extract. Mite
      pretreatment enhanced Na2SO3-induced CD49f down-regulation; Na2SO3 and/or mite
      extract down-regulated CD49b expression of A549 cells. These findings indicate
      that a synergistic effect of mite extract and sulfite can severely disrupt the
      airway bronchial epithelial barrier.

PMID- 18327424
TI  - Low rate of nasopharyngeal carriage and high rate of ampicillin resistance for
      Haemophilus influenzae among healthy children younger than 5 years old in
      northern Taiwan.
AB  - BACKGROUND AND PURPOSE: Surveillance data of colonization by Haemophilus
      influenzae in Taiwan are lacking. This study aimed to define the nasopharyngeal
      carriage rate of H. influenzae among children younger than 5 years in northern
      Taiwan, and to determine the antibiotic susceptibility, serotype and the clonal
      relationship of these isolates. METHODS: Nasopharyngeal specimens were obtained
      from 511 healthy children younger than 5 years. All H. influenzae isolates were
      serotyped. The minimal inhibitory concentrations for various antibiotics were
      determined. Pulsed-field gel electrophoresis (PFGE) was used for clonal analysis.
      RESULTS: Among 511 children, 269 (52.6%) had been vaccinated with at least one
      dose of H. influenzae type b (Hib) conjugate vaccine, 236 (46.2%) were
      unvaccinated and 6 (1.2%) had no vaccination records available. Twenty six H.
      influenzae strains were isolated. There were three Hib isolates and the others
      were nontypeable H. influenzae (NTHi). The carriage rate for Hib was 0.6% (3/511)
      and of NTHi was 5% (23/511). Three (1.27%) of the 236 unvaccinated children were
      carriers of Hib, whereas none of the 269 vaccinated children carried Hib. Two out
      of the three Hib isolates and 14 (60.9%) of 23 NTHi isolates were ampicillin
      resistant. Multidrug resistance was found in 7 (26.9%) of the isolates. Among the
      isolates, 61.5% were beta-lactamase producers; there were no beta-lactamase
      negative ampicillin-resistant isolates. The PFGE restriction patterns showed a
      wide diversity of genotypes. CONCLUSIONS: There is very low nasopharyngeal
      carriage of Hib among children younger than 5 years in northern Taiwan. This may
      explain why the incidence of invasive Hib disease is also low in Taiwan. In
      addition, we found a high prevalence of beta-lactamase-positive ampicillin
      resistant nasopharyngeal H. influenzae isolates.

PMID- 18327425
TI  - Clinical application of the rapid pneumococcal urinary antigen test in the
      treatment of severe pneumonia in children.
AB  - BACKGROUND AND PURPOSE: To evaluate the efficacy of the pneumococcal urinary
      antigen test (PUAT) in severe pediatric pneumonia. METHODS: The study enrolled
      245 pediatric patients with severe pneumonia. Patients were divided into four
      groups; groups 1 and 2 received PUAT, while groups 3 and 4 did not. Additionally,
      PUAT-positive group 1 patients were treated with penicillin, while PUAT-negative
      patients received ampicillin-sulbactam or cefuroxime. Group 2 patients were
      treated empirically without following the group 1 protocol. Group 3 patients were
      treated following the guideline of the Infectious Diseases Society of Taiwan
      (IDST), and group 4 patients were treated empirically without following the IDST
      guideline. Treatment was assessed by the duration of fever. RESULTS: Treatment
      was most effective for group 1 and least effective for group 4. Group 2 treatment
      was superior to group 3 treatment. Multivariate regression analysis of groups 1
      and 2 revealed that the use of PUAT (groups 1 and 2) was associated with superior
      response in comparison with group 4. CONCLUSION: Application of PUAT and adequate
      antimicrobial treatments in the initial stage for pediatric patients with severe
      pneumonia resulted in improved outcome as assessed by shortening of the duration
      of fever.

PMID- 18327426
TI  - Clinical features and prognostic factors in childhood pneumococcal meningitis.
AB  - BACKGROUND AND PURPOSE: Despite progress in antibiotic therapy and intensive
      care, childhood pneumococcal meningitis remains a devastating disease, with
      morbidity and mortality rates among the highest of any cause of bacterial
      meningitis. We conducted this study to find the factors associated with disease
      outcome in clinical settings. METHODS: All pediatric medical charts during the
      period from January 1984 to December 2003 with the diagnosis of pneumococcal
      meningitis were reviewed. We recorded patients' symptoms and signs, laboratory
      data and treatments. Outcome and neurological complications were also analyzed.
      RESULTS: In total, 40 episodes of pneumococcal meningitis from 37 patients aged 3
      months to 10 years were identified. Predisposing factors were found in 13
      patients (35.1%), and included recent history of head injury, immunocompromised
      states and cranial base anomaly. All patients had fever during illness. Patients
      older than 24 months of age tended to complain of nuchal rigidity (19/21, 90.5%)
      and those younger than 6 months of age tended to present irritability (6/7,
      85.7%). The overall mortality rate was 25% (10 out of 40 episodes). The following
      variables were associated with mortality after statistical analysis:
      consciousness disturbance, shock, endotracheal tube intubation and hyponatremia
      (sodium <130 mEq/L) at admission (p=0.001, p<0.001, p<0.001, and p=0.012,
      respectively). Also, laboratory findings of less than 20/mm3 white cell count in
      cerebrospinal fluid (CSF), lower CSF glucose level and CSF-to-blood glucose ratio
      were significantly higher in non-survivors (p=0.003, p=0.009, p=0.027). Variables
      associated with morbidity were seizure attack and focal neurological sign
      occurring hospitalization (p=0.017, p=0.017). CONCLUSIONS: The mortality of
      childhood pneumococcal meningitis remains high. If a child with pneumococcal
      meningitis presents with consciousness disturbance, hypotension, endotracheal
      intubation or hyponatremia at admission, the disease mortality rate increases.
      CSF findings with low white cell count, low glucose level and CSF-to-blood
      glucose ratio are also warning signs of a bad outcome. Seizure attack and focal
      neurological sign are the factors associated with further neurological sequelae.

PMID- 18327427
TI  - An open, randomized, comparative study of clarithromycin and erythromycin in the
      treatment of children with community-acquired pneumonia.
AB  - BACKGROUND AND PURPOSE: This study aimed to evaluate the efficacy and safety of
      clarithromycin and erythromycin in the treatment of community-acquired pneumonia
      in children. METHODS: Children with community-acquired pneumonia were randomly
      assigned to receive 10-day regimens of either clarithromycin 15 mg/kg/day, twice
      a day, or erythromycin 30-50 mg/kg/day, four times daily. RESULTS: A total of 97
      children entered this study, including 26 with Mycoplasma pneumoniae infection,
      15 with Chlamydia pneumoniae infection, and 6 with mixed mycoplasma and chlamydia
      infections. Fifty and 47 children received clarithromycin and erythromycin
      treatment, respectively. Three children withdrew from the study because the
      identified pathogens were resistant to the study drugs. All 47 children with
      mycoplasma or chlamydia infection were cured clinically. Delayed defervescence,
      defined as a fever lasting for more than 72 h after treatment, was observed in 4
      of 22 clarithromycin-treated children (18%) and in 3 of 15 erythromycin-treated
      children (20%) [p>0.05]. Gastrointestinal side effects, including vomiting,
      abdominal pain and diarrhea, were observed in 3 of 50 children (6%) receiving
      clarithromycin and in 11 of 49 children (22%) receiving erythromycin (p=0.039).
      Excluding children with abnormal pretreatment liver function, abnormal liver
      function after treatment was observed in only one child, treated with
      erythromycin. Post-treatment eosinophil and platelet counts were significantly
      elevated after treatment in both groups. CONCLUSIONS: Clarithromycin showed
      efficacy equivalent to erythromycin for the treatment of mycoplasma or chlamydia
      pneumonia in children. However, the tolerability of clarithromycin was superior
      to that of erythromycin.

PMID- 18327428
TI  - Subdural empyema in children--20-year experience in a medical center.
AB  - BACKGROUND AND PURPOSE: Subdural empyema (SDE) is a serious neurological
      condition in children and adults. Although otorhinolaryngeal infections are
      regarded as the most important predisposing factors in the literature, this has
      not been our experience. This study reviewed clinical data on pediatric patients
      with SDE at our institution over the last 20 years. METHODS: Charts of children
      hospitalized in Mackay Memorial Hospital from 1985 to 2005, with a final
      diagnosis of SDE were reviewed. Gender, predisposing factors, symptoms and signs,
      bacteriologic data, diagnostic work-up, treatment procedures, and outcome were
      collected and analyzed. RESULTS: In total, 31 patients were enrolled. Twenty
      seven of them (87.1%) were below the age of one year. The male-to-female ratio
      was 1.21. Only 3 patients (9.7%) had prior otorhinolaryngeal infections; 6
      patients (19.4%) had SDE following head trauma or surgery. The leading clinical
      manifestations were fever (96.8%), seizure (70.1%), and focal neurological signs
      (58.1%). The most common pathogens included Streptococcus pneumoniae (16.1%),
      group B Streptococcus (12.9%), Haemophilus influenzae type b (12.9%), Salmonella
      spp. (12.9%), Escherichia coli (9.7%) and Pseudomonas aeruginosa (9.7%).
      Cerebrospinal fluid leukocyte counts and protein levels were usually high and the
      glucose levels were usually low. SDE was first suspected or found via brain
      sonography in 9 infants. Nine patients (29.0%) received only medical treatment
      for SDE. Three patients (9.7%) died--all were infected by S. pneumoniae. Twelve
      patients (38.7%) recovered without neurological sequelae. CONCLUSIONS: In the
      past 20 years, most of our cases of pediatric SDE occurred in infancy, and only
      one-tenth of them had prior otorhinolaryngeal infections. Brain sonography could
      be a helpful tool for early diagnosis of SDE in infancy.

PMID- 18327429
TI  - Prevalence of Blomia tropicalis in wheezing children in central Taiwan.
AB  - BACKGROUND AND PURPOSE: In a previous study, we found that wheezing children in
      rural central Taiwan had a significantly lower average sensitization rate to
      Dermatophagoides pteronyssinus (Der p) than those in Taipei city. We propose that
      Blomia tropicalis (Blo t) might be the major mite allergen in rural central
      Taiwan. METHODS: Using the preserved sera from our previous study, we
      retrospectively measured specific immunoglobulin E (IgE) antibody to Blo t and
      analyzed the correlation between Blo t and Der p in wheezing children in rural
      central Taiwan. A total of 2206 children with physician-diagnosed asthma and
      wheezing were enrolled and categorized among five age groups. The sensitization
      rate and level of specific IgE antibody to Blo t were analyzed. RESULTS: The age
      specific sensitization rates and the level of specific IgE antibody to either Blo
      t or Der p increased progressively with increasing age, being greatest in the age
      group 8 to 12 years. A significant positive correlation existed between
      sensitization rate and age for both Blo t and Der p (p=0.001). Specific IgE
      antibody to Blo t was undetectable in patients younger than 1.5 years. A
      significant positive correlation also existed between age and anti-Blo t IgE
      antibody level (p<0.003). However, the allergen-specific IgE level was lower for
      Blo t than Der p (p<0.005) in all age groups. CONCLUSIONS: Blo t might be the
      major mite allergen to associated with early wheeze and atopic asthma in rural
      central Taiwan.

PMID- 18327430
TI  - Cryptosporidiosis in immunocompromised patients in the Islamic Republic of Iran.
AB  - BACKGROUND AND PURPOSE: Cryptosporidiosis is a parasitic zoonosis, which is
      prevalent all over the world. The manifestation of the disease is either self
      limiting acute diarrhea in immunocompetent individuals, or potentially fatal
      chronic diarrhea in immunocompromised patients. METHODS: In this study, which was
      conducted in Tehran, 214 patients from ten health centers were investigated.
      Stool samples were collected, fixed and examined by three methods: acid-fast
      staining, auramin phenol fluorescence and direct fluorescence using monoclonal
      antibody. RESULTS: Overall, 1.4% of all patients and 6.3% of diarrheal patients
      were infected by Cryptosporidium. The results revealed three cases of
      cryptosporidiosis, including two cases of acquired immunodeficiency syndrome
      (AIDS) and one of acute myeloid leukemia (AML). The prevalence of infection in
      subjects with AIDS or AML who were suffering from diarrhea was 33.4% and 11.1%,
      respectively. The duration of disease in infected patients lasted for weeks, and
      was terminated by death in two AIDS patients. In the patient with AML, diarrhea
      lasted for 18 days, and stopped after discontinuation of immunosuppressive
      therapy. CONCLUSIONS: Immunosuppressed people are at a significant risk of severe
      or even fatal Cryptosporidium infections.

PMID- 18327431
TI  - Frequency and phenotypic analysis of CD4+CD25+ regulatory T cells in children
      with juvenile idiopathic arthritis.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to investigate the frequency of
      CD4(+)CD25(+) regulatory T cells and their phenotypic expression in peripheral
      blood of children with active and non-active juvenile idiopathic arthritis (JIA)
      and healthy controls, to determine if their frequency or phenotypic expression is
      involved in the immunoregulation of this disease. METHODS: From October 2004 to
      October 2005, 55 JIA patients and 55 age- and gender-matched healthy controls
      were enrolled in the study at National Taiwan University Hospital. Flow cytometry
      was used to determine the frequency of CD4(+)CD25(+) and CD4(+)CD25(hi) in CD4(+)
      T cells and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression on
      CD4(+)CD25(+) by tricolor staining. Basic profiles, medication history, clinical
      symptoms and laboratory data were obtained by chart review and outpatient
      department interviews. RESULTS: There was no significant difference in expression
      of CD4(+)CD25(+) T cells between patients with inactive JIA and normal controls
      (13.74+/-3.25% vs 12.85+/-3.68%, p>0.05). The expression of CD4(+)CD25(hi) T
      cells was significantly lower in inactive JIA patients than in normal controls
      (1.89+/-1.01% vs 2.76+/-1.28%, p<0.01). The expression of CTLA-4 on CD4(+)CD25(+)
      T cells was also significantly lower in inactive JIA patients compared with
      controls (4.37+/-2.02% vs 6.33+/-2.57%, p<0.001). CONCLUSION: We speculate that a
      decreased frequency of CD4(+)CD25(hi) regulatory T cells and lower level of CTLA
      4 expression on CD4(+)CD25(+) regulatory T cells might play a role in the
      immunoregulation of JIA.

PMID- 18327432
TI  - Tai Chi Chuan training improves the pulmonary function of asthmatic children.
AB  - BACKGROUND AND PURPOSE: Tai Chi Chuan, a traditional Chinese exercise, is thought
      to improve cardiopulmonary function in patients with chronic disease. This study
      investigated the effect of Tai Chi Chuan on the pulmonary function and daily
      symptoms of asthmatic children. METHODS: Thirty asthmatic children were enrolled
      into the study. Fifteen of the 30 children participated in a 12-week Tai Chi
      Chuan program and the remaining 15 constituted the control group. Prior to study
      participation, the pulmonary function of all enrolled children was assessed at
      rest, after exercise, and after exercise plus iced water. A 3-day symptoms
      questionnaire was also completed and a score obtained after each pulmonary
      function test. RESULTS: There were no significant differences between the two
      groups in baseline pulmonary function and severity of asthmatic symptoms before
      study commencement, at rest, after exercise, or after exercise plus iced water.
      However, after the 12-week program, children in the Tai Chi Chuan group had a
      significant improvement in pulmonary function compared to the control group.
      Although there were no significant differences in post-training symptom scores at
      rest and after exercise between the two groups, under the stronger challenge of
      exercise plus iced water, children in the Tai Chi Chuan group had milder symptoms
      than those in the control group. CONCLUSION: Our data show that Tai Chi Chuan can
      improve the pulmonary function of asthmatic children. However, long-term follow
      up is required to determine the impact of Tai Chi Chuan on the severity of
      asthmatic symptoms.

PMID- 18327433
TI  - A randomized crossover clinical study showing that methylphenidate-SODAS improves
      attention-deficit/hyperactivity disorder symptoms in adolescents with substance
      use disorder.
AB  - Our objective was to evaluate the effectiveness of a long-acting formulation of
      methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD)
      symptoms in an outpatient sample of adolescents with ADHD and substance use
      disorders (SUD). Secondary goals were to evaluate the tolerability and impact on
      drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled
      crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD
      symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to
      either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse
      order). The primary outcome measures were the Swanson, Nolan and Pelham Scale,
      version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also
      evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating
      Scale and subject reports of drug use during the study. The sample consisted of
      marijuana (N = 16; 100%) and cocaine users (N = 7; 43.8%). Subjects had a
      significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all
      analyses) during MPH-SODAS treatment compared to placebo. No significant effects
      for period or sequence were found in analyses with the SNAP-IV and CGI scales.
      There was no significant effect on drug use. MPH-SODAS was well tolerated but was
      associated with more severe appetite reduction than placebo (P < 0.001). MPH
      SODAS was more effective than placebo in reducing ADHD symptoms in a non
      abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical
      trials, with larger samples and SUD intervention, are recommended.

PMID- 18327434
TI  - Interrelationship between serum and sputum inflammatory mediators in chronic
      obstructive pulmonary disease.
AB  - Little is known about airway inflammatory markers in chronic obstructive
      pulmonary disease (COPD). The objective of the present study was to identify and
      try to correlate pulmonary and peripheral blood inflammatory markers in COPD. In
      a cross-sectional study on patients with stable COPD, induced sputum and blood
      samples were collected for the determination of C-reactive protein, eosinophilic
      cationic protein, serum amyloid A protein, alpha-1 antitrypsin (alpha-1AT), and
      neutrophil elastase. Twenty-two patients were divided into two groups according
      to post-bronchodilator forced expiratory volume in the first second (%FEV1):
      group 1 (N = 12, FEV1 <40%) and group 2 (N = 10, FEV1 > or =40%). An increase in
      serum elastase, eosinophilic cationic protein and alpha-1AT was observed in serum
      markers in both groups. Cytology revealed the same total number of cells in
      groups 1 and 2. There was a significantly higher number of neutrophils in group 1
      compared to group 2 (P < 0.05). No difference in eosinophils or macrophages was
      observed between groups. Serum elastase was positively correlated with serum
      alpha-1AT (group 1, r = 0.81, P < 0.002 and group 2, r = 0.83, P < 0.17) and
      negatively correlated with FEV1 (r = -0.85, P < 0.03 and -0.14, P < 0.85,
      respectively). The results indicate the presence of chronic and persistent
      pulmonary inflammation in stable patients with COPD. Induced sputum permitted the
      demonstration of the existence of a subpopulation of cells in which neutrophils
      predominated. The serum concentration of all inflammatory markers did not
      correlate with the pulmonary functional impairment.

PMID- 18327435
TI  - Yellow fever and public health in Brazil.

PMID- 18327436
TI  - [Home care and its relationship to the work environment in health].
AB  - This paper discusses home care as a service that has expanded in the public and
      private health system, while arguing for the possibility that such care can
      leverage a significant impact on the population's quality of life and health. The
      article presents home care as a strategic possibility for reorganizing the health
      system, by means of integration between health workers and health institutions,
      and considers its possible political, economic, and technical impacts on the
      health system, health workers, and users of the service.

PMID- 18327437
TI  - Occupational exposure to acid mists and periodontal attachment loss.
AB  - This study investigated the hypotheses that occupational exposure to acid mists
      is positively associated with periodontal disease, assessed by periodontal
      attachment loss. The study sample included 530 male workers at a metal processing
      factory. Data were obtained from interviews and oral examinations. Periodontal
      attachment loss was defined as >or= 4mm at probing, in at least one tooth. A job
      exposure matrix was utilized for exposure evaluation. Exposure to acid mists was
      positively associated with periodontal attachment loss >or= 4mm at any time
      (prevalence ratio, PR(adjusted) = 2.17), past (PR(adjusted) = 2.11), and over 6
      years of exposure (PR(adjusted) = 1.77), independently of age, alcohol
      consumption, and smoking, and these results were limited to workers who did not
      use dental floss. Exposure to acid mists is a potential risk factor for
      periodontal attachment loss, and further studies are needed, using longitudinal
      designs and more accurate exposure measures.

PMID- 18327438
TI  - [Prevalence of symptoms of anorexia nervosa and dissatisfaction with body image
      among female adolescents in Florianopolis, Santa Catarina State, Brazil].
AB  - The objective of this study was to identify the prevalence of symptoms of
      anorexia nervosa (EAT+) and dissatisfaction with body image among female
      adolescents in Florianopolis, Santa Catarina State, Brazil. The proportional
      sample (1,148 adolescents) was stratified according to position of schools in the
      socio-geographic regions and public/private school classification, and was
      subsequently distributed according to primary and secondary schools. EAT+ was
      identified through the Eating Attitudes Test and evaluation of body image through
      the Body Shape Questionnaire. Prevalence rates for EAT+ and dissatisfaction with
      body image were 15.6% and 18.8%, respectively. EAT+ was associated with age (10
      13y) (OR = 1.542; p = 0.046); overweight/obesity (OR = 2.075; p < 0.001);
      dissatisfaction with body image (OR = 14.392; p < 0.001); and public schools (OR
      = 1.423; p = 0.041). Multiple logistic regression showed dissatisfaction with
      body image as the strongest independent risk factor for symptoms of anorexia
      nervosa (OR = 16.7; p < 0.001). Adolescents in Florianopolis show EAT+ rates
      similar to those observed in other regions of Brazil.

PMID- 18327439
TI  - [Mixed linear regression model for longitudinal data: application to an
      unbalanced anthropometric data set].
AB  - A longitudinal data set is characterized by a time sequence of two or more
      observations from each individual. In cohort studies, these data are usually not
      balanced. A data set related to longitudinal height measurements in children of
      HIV-infected mothers was recorded at the university hospital of the Federal
      University in Minas Gerais, Brazil. The objective was to assess the application
      of the mixed effect model to this unbalanced data set. At six months of age, on
      average boys were 1.8 cm taller than girls, and seroreverter infants were 2.9 cm
      taller than their HIV+ peers. At 12 months of age, on average boys were 2.4 cm
      taller than girls and seroreverter children were 3.5 cm taller than HIV+ ones. In
      addition to describing longitudinal height behavior, this model also includes the
      growth rate estimation for this infant population by gender and group.

PMID- 18327440
TI  - [Consenting to uncertainties: informed consent and (de)regulation of assisted
      reproductive technologies].
AB  - This article aims to analyze the characteristics in the creation and utilization
      of self-knowledge by physicians and "laypersons" involved in assisted
      reproductive technologies, based on a comparison of their respective discursive
      practices concerning expectations, uncertainties, and responsibilities associated
      with these techniques in Portugal. Physicians evaluate the (un)certainties in the
      application of these techniques based on naturalist and essentialist categories.
      However, such arguments are then used as an ideological instrument to disguise
      the lack of a "scientific" explanation for the failures, thereby reproducing the
      belief in the "miraculous" nature of scientific and technological progress. The
      lay understanding of the benefits and limitations of these techniques reflects a
      reverential attitude towards medicine and the rationalist paradigm of the
      biomedical perspective, although it is possible to glimpse some spaces for
      autonomy and resistance vis-a-vis the medical proposals. The uncertainties of
      these techniques are conceptualized as exceptional and intrinsic effects of
      medical practice, to which one is required to submit individually. Women are
      particularly identified as the main parties responsible for maximizing the
      probability of "success" with these techniques.

PMID- 18327441
TI  - [Health profile of the elderly in Brazil: analysis of the 2003 National Household
      Sample Survey using the Grade of Membership method].
AB  - The aim of this study was to identify functional disability and health profiles
      of the elderly in Brazil, as well as their prevalence rates, based on the
      National Household Sample Survey for 2003. The sample size was 33,786 elderly
      individuals. Grade of Membership was used to define the profiles: "healthy
      elderly" (Profile 1), whose pure types had a lower probability of disability and
      chronic illness; "elderly with mild functional disability" (Profile 2), whose
      pure types had mainly hypertension and lower back problems and were independent
      in activities of daily living, although with high difficulty in mobility; and
      "elderly with severe disability" (Profile 3), with higher probability of chronic
      illness, high difficulty with activities of daily living, and high dependency in
      terms of mobility. In conclusion, the profiles indicate that a consistent
      approach to functional disability is essential for promoting the health of the
      elderly.

PMID- 18327442
TI  - Overcoming health inequity: potential benefits of a patient-centered open-source
      public health infostructure.
AB  - The past 20 years have witnessed an astonishing increase in computational power
      and an incredible reduction in the cost of contemporary computer systems, but the
      public health infostructure in most countries has not changed significantly. This
      article discusses the potential benefits of applying patient-centered
      infostructure at the primary medical "points-of-care" services, based on
      networked integrated open-source technology and programming standards to develop
      tools to detect and reduce health inequalities. Such systems, which could be
      implemented from the local to the national level, would enable the expansion of
      evidence-based medicine, clearer identification of health inequalities, and more
      accurate cost-benefit analyses. In addition, the public health sector could link
      such databases to traditional Electronic Patient Record (EPR) systems at a
      greatly reduced cost by promoting the use of standards-based formats for data
      transfer and storage. Ultimately, the new health infostructure would help
      decrease health inequity. In fact, developing countries like Brazil, India, and
      South Africa are well-positioned to take advantage of the open-source movement
      and "leapfrog" countries burdened by legacy systems.

PMID- 18327443
TI  - [Self-reported vaginal discharge among pregnant women in an urban area in
      Southern Brazil: prevalence and associated factors].
AB  - The purpose of this study was to determine the prevalence and risk factors
      associated with self-reported vaginal discharge among pregnant women in the city
      of Rio Grande, South Brazil. Using a cross-sectional design, a standard interview
      was applied to pregnant women at home by previously trained interviewers,
      covering the following: demographic, reproductive, and socioeconomic data,
      household conditions, health care, and illnesses during pregnancy, including
      vaginal discharge. The chi-square test was used to compare proportions, and
      Poisson regression was used in the multivariate analysis. Among the 339 pregnant
      women interviewed, 52% reported vaginal discharge. The following variables were
      significantly associated with the outcome: age (prevalence rate, PR = 1.49),
      marital status (PR = 1.31), urinary tract infection (PR = 1.56), hyperglycemia
      (PR = 1.48), use of an intrauterine device (PR = 2.35), and history of preterm
      delivery (PR = 1.37), with oral contraception showing a protective effect (PR =
      0.79). Prevalence of self-reported discharge was high among this group of
      pregnant women. Several risk factors were also identified for the disease under
      study. These findings can contribute to the implementation of preventive
      interventions.

PMID- 18327444
TI  - [Self-perceived health and associated factors in industrial workers from Santa
      Catarina State, Brazil].
AB  - The purpose of this study was to determine the prevalence of negative self
      perceived health and associated factors among industrial workers in Santa
      Catarina State, in southern Brazil. A cross-sectional investigation was conducted
      with a representative sample of 2,574 subjects (62.5% men). Negative self
      perceived health (fair or poor) was the outcome investigated in association with
      demographic, socioeconomic, and other health indicators. Multivariate analysis
      was performed through logistic regression based on a hierarchical model. Negative
      self-perceived health was exceptional (11.8%), but positively associated with
      age, leisure physical activity, perceived quality of sleeping, perceived stress,
      and sex. Meanwhile, the outcome was negatively associated with family income and
      schooling. Workers with higher physical demands and BMI < 18.5 and > 30 showed
      increased odds of negative self-perceived health. No significant differences were
      found for marital status, binge drinking, or smoking. Few associations were
      observed for females.

PMID- 18327445
TI  - [Assistance for customers with sexually transmitted diseases at pharmacies in the
      Federal District, Brazil: an intervention study].
AB  - A quantitative survey was conducted to analyze the type of assistance provided by
      pharmacy employees for cases of STDs. Simulated customer visits and interviews
      were conducted in 70 pharmacies in Brasilia and Taguatinga, Brazil, randomly
      assigned to two groups, one of which participated in educational activities on
      STDs. There were 411 simulated client visits to the pharmacies, with the
      following results: recommendation to seek medical care in 30% of cases, while in
      70% of cases the pharmacy employees themselves recommended some drug treatment
      (although only 16.4% admitted to such practice). None of these suggested
      treatments was appropriate, based on the syndromic approach. Recommendations for
      prevention and treatment of partners were rare. Pharmacists recommended
      consulting a physician more frequently than attendants, and the latter
      recommended medicines more frequently than the former. Pharmacy workers had only
      superficial knowledge of STDs. After an educational intervention, none of the
      indicators showed a significant improvement in either group. The observations
      point to the need for regulation and intervention to publicize educational
      practices for the control of diseases like STDs and for the rational use of
      medicines in pharmacies.

PMID- 18327446
TI  - [Socio-demographic, lifestyle, gynecological, and obstetric predictors of serum
      or plasma concentrations of homocysteine, folic acid, and vitamins B12 and B6
      among low-income women in Sao Paulo, Brazil].
AB  - This study examined the socio-demographic, lifestyle, gynecological, and
      obstetric factors associated with serum or plasma concentrations of homocysteine,
      folic acid, and vitamins B12 and B6 among low-income women in Sao Paulo, Brazil.
      Serum concentrations of folic acid and vitamin B12 were measured by
      fluoroimmunoassay, while plasma vitamin B6 and homocysteine levels were measured
      by reversed-phase high performance liquid chromatography. Independent variables
      were initially selected by Pearson correlation or Kruskal-Wallis test (p < 0.20).
      Based on cut-off values, altered concentrations of homocysteine, folic acid, and
      vitamins B12 and B6 were found in 20%, 6%, 11%, and 67% of participants,
      respectively. Age was positively correlated with vitamin B6 and homocysteine
      plasma concentrations (p < 0.001). Body mass index was positively correlated with
      vitamin B6 plasma concentration (p < 0.001). Multiple linear regression models
      accounted for 10.2%, 5.8%, 14.4%, and 9.4% of folic acid, vitamins B12 and B6,
      and homocysteine plasma or serum concentrations, respectively. In this study,
      socio-demographic, lifestyle, gynecological, and obstetric variables showed
      important predictive value for serum or plasma levels of the biochemical
      indicators assessed.

PMID- 18327447
TI  - [The changing age distribution of the Brazilian population in the first half of
      the 21st century].
AB  - Brazil is currently in an advanced stage of both the mortality and fertility
      transitions, which allows one to confidently forecast the age distribution and
      population size over the next four decades. Whereas the elderly population (>
      or=65 years) will increase at high rates (2-4% per year), the young population
      will decline. According to United Nations projections, the elderly population
      will increase from 3.1% of the population in 1970 to 19% in 2050. Meanwhile,
      within the young and adult populations, growth rates will vary among different
      age groups, ranging from negative to positive values. The changing age
      distribution of the Brazilian population brings opportunities and challenges that
      could lead to serious social and economic issues if not dealt with properly in
      the coming decades.

PMID- 18327448
TI  - [The Hospital Information System of the Brazilian National Unified Health System:
      a preliminary evaluation of performance in monitoring RhD hemolytic disease of
      the newborn].
AB  - This study aimed to evaluate the adequacy of the Hospital Information System of
      the National Unified Health System (SIH-SUS) in identifying cases of RhD
      hemolytic disease of the newborn (HDN) at the Fernandes Figueira Institute
      (IFF/FIOCRUZ) from 1998 to 2003. Neonatal records, data from the Medical
      Archives, and AIH (Hospital Admissions Authorization Form) data consolidated in
      the SIH-SUS were analyzed. Cases were identified according to the following
      fields: principal diagnosis, secondary diagnosis, and procedure performed. During
      the period studied, 194 cases of HDN were diagnosed. The Medical Archives
      registered 148 newborns with HDN, however only 147 AIHs were issued and 145
      consolidated in the SIH-SUS. Among these 145 cases, 84 cited HDN as the principal
      diagnosis, while secondary diagnosis identified 38 additional cases and the
      procedures performed failed to identify any further cases. Thus, the SIH-SUS
      identified only 122 (62.9%) of the 194 cases of HDN treated at the IFF/FIOCRUZ.
      Although it is necessary to evaluate other units, the SIH-SUS does not appear to
      be reliable for monitoring HDN. Additional studies are essential for employing
      secondary administrative data in the context of epidemiological surveillance.

PMID- 18327449
TI  - [The Brazilian version of the Fear Avoidance Beliefs Questionnaire].
AB  - The aim of the present study was to investigate the psychometric properties and
      validate the Portuguese version of the Fear Avoidance Beliefs Questionnaire (FABQ
      Brazil). This instrument assesses how beliefs and fear of individuals with lower
      back pain affect two subscales related to their physical activities (FABQ-Phys)
      and work (FABQ-Work). The questionnaire was translated into Brazilian Portuguese,
      following the recommended methodology, and applied to 53 individuals with non
      specific chronic lower back pain. The test-retest intra-class correlation
      coefficients (ICC = 0.84 and 0.91) and the internal consistency (Cronbach's =
      0.80 and 0.90) for FABQ-Phys and FABQ-Work, respectively, were acceptable. The
      stepwise multiple regression analyses revealed statistically significant
      correlations between all isolated items with their respective subscales, and the
      set of the items explained 99% of the changes in scores for each subscale. No
      significant correlations were found between the subscales; however, both the FABQ
      Phys and FABQ-Work subscales were positively associated with pain intensity
      (visual numerical scale) and degree of disability (Roland Morris Questionnaire).
      These findings supported the evidence that the FABQ-Brazil showed adequate
      psychometric properties for individuals with chronic lower back pain.

PMID- 18327450
TI  - [Work in mental health: a job satisfaction and work impact study].
AB  - Knowledge of job satisfaction and work impact among psychiatric staff is highly
      useful for policymakers and mental health professionals. Since there are few
      studies on this issue in Brazil, a cross-sectional study was carried out among
      mental health professionals. Data were collected for 133 professionals from 4
      mental health services in Rio de Janeiro, using SATIS-BR and IMPACTO-BR scales
      and a socio-demographic questionnaire. Statistical associations were analyzed
      using the Mann-Whitney, Kruskal-Wallis, and chi-square tests and multiple linear
      regression. SPSS 10.1 for Windows was used for statistical analyses. Mean
      satisfaction was 3.30 and mean work impact was 2.08 (on a scale from 1 to 5).
      62.4% of subjects reported moderate satisfaction. Mental health workers with less
      schooling showed higher satisfaction. Work impact was not associated with any
      explanatory variable. The results for job satisfaction were similar to those of
      other studies. Work impact was very low. Unlike studies from the United States
      and Europe, there were no differences between the community-based and in-hospital
      staff.

PMID- 18327451
TI  - [Characteristics of individuals and care delivered at the psychosocial care
      centers for children and adolescents].
AB  - This study aimed to provide an understanding of diagnosis, demographic
      characteristics, and treatment procedures for children and adolescents attending
      Psychosocial Care Centers (CAPSIS) in Brazil, 2003. It was a cross-sectional
      descriptive study using secondary data. The analysis considered three groups of
      variables related to: (a) the nature of the services; (b) patient profile; and
      (c) types of care. Seven CAPSIS that had recorded their procedures during all 12
      months of 2003 participated in the study. The units involved treated 1,456
      individuals, 62.8% of whom were males 11-13 years of age. Nearly half (49.3%)
      were treated in non-intensive care. The most frequent diagnoses were behavioral
      and emotional disorders (44.5%). There was no record of treatment related to use
      of psychoactive substances. The proportion of severe disorders was 19.4%. The
      CAPSIS operate in similar fashion to older outpatient units, but treat a variety
      of problems, creating a record according to types of activities. These services
      fill a historical gap in public mental health care for children and adolescents.

PMID- 18327452
TI  - [Evaluation of the Charlson comorbidity index among inpatients in Ribeirao Preto,
      Sao Paulo State, Brazil].
AB  - The objective of this article was to evaluate the use of the Charlson comorbidity
      index (CCI) to predict inpatient death in Ribeirao Preto, Sao Paulo State,
      Brazil. 54,680 hospitalizations from January 1996 to December of 1997 were
      analyzed. Two International Classification of Diseases adaptations of CCI were
      compared, and the 30 clinical conditions assessed by the Charlson index were
      reviewed. Logistic regression was used to evaluate the models' capacity to
      predict inpatient death. The baseline model included: age, sex, and principal
      diagnosis. Differences in ICD adaptations showed little effect on the models'
      discriminatory capacity. Revision of the 30 clinical conditions increased the
      model's discriminatory capacity to predict death (C statistic = 0.73), as
      compared to the model with the original CCI (C statistic = 0.72). All tested
      models had a reduced effect on the baseline model's discriminatory capacity (C
      statistic = 0.70). The results show the importance of Brazil having an
      information system that allows a complete description of hospital morbidity in
      order to monitor health service performance.

PMID- 18327453
TI  - [Probabilistic record linkage: an application to severe maternal morbidity (near
      miss) and maternal mortality].
AB  - This article presents an experience with record linkage from the Brazilian
      Hospital Information System (SIH) with the Mortality Information System (SIM),
      and the SIH with itself, applied to severe maternal morbidity (near miss) and
      maternal mortality. This was an empirical study using Brazilian data for the
      state capitals and Federal District in 2002. For the two linkages separately
      applied in each capital, a three simple step blocking strategy was established,
      plus related multiple steps and also two clerical review strategies. From the
      total number of true pairs found after the two linkages, simple steps failed to
      find fewer than 8%, while the multiple step strategy failed to find only 0.7%.
      This approach allowed exploring the issue of severe maternal morbidity and
      mortality in these databases. The number of pairs found and reviewed under the
      multiple steps strategy was lower than the sum of pairs obtained with the three
      simple steps, and fewer pairs were lost. However, for the record linkage of the
      SIH with itself, both strategies are suggested.

PMID- 18327454
TI  - [Case-resolving capacity of health care services according to a household survey:
      users' perceptions].
AB  - The objective of this study was to identify the case-resolving capacity of health
      care services used by individuals who reported a health problem within two weeks
      prior to the interview and to unveil their respective perceptions of the solution
      to the problem. Data were obtained from a household morbidity survey including
      10,199 interviewees, performed in the southwestern area of the city of Sao Paulo,
      Brazil, in 1989/1990. Some health problem was reported by 31.3% of interviewees,
      and 47.7% sought help to solve their problem. Primary health services were the
      main gateway into the health system (35.7%), followed by hospitals (25.4%), and
      outpatient clinics (24.3%). The case-resolving capacity in the medical services
      was greater than 90%; 44.5% had their problem solved, 35.5% were under treatment,
      and 10.5% reported that their problem had not been solved. The largest proportion
      of problems solved belonged to respiratory and digestive system, infectious and
      parasitic diseases, and ill-defined symptoms, signs, and conditions. Due to the
      large proportion of individuals still in treatment, this study does not allow one
      to conclude that the health care services had a high case-resolving capacity,
      although they were capable of handling the patient demand.

PMID- 18327455
TI  - [Monitoring of infant growth by health services in Pernambuco State, Brazil].
AB  - A situational diagnosis was performed on infant growth monitoring in Greater
      Metropolitan Recife and in the interior of the State of Pernambuco, Brazil, using
      the database from the Survey on Maternal and Child Health in the State of
      Pernambuco, 1998, which included 816 infants (< 1 year of age) and 120 health
      units. Epi Info version 6.04 was used for the analysis. In the health services
      infrastructure, 15.8% of the health units lacked infant scales and the Child's
      Health Card, and 75.4% lacked the guidelines for monitoring growth and
      development. Of these variables, the first two showed a difference between the
      two study areas. As for process evaluation, 81.2% of the mothers had the Child's
      Health Card, 53.1% of the children had been weighed, and only 21% had been
      measured. Mothers had received insufficient orientation. These variables also
      showed differences between the two study areas. Care for children with
      nutritional risk received little attention in the two areas, although there was a
      difference between the interior and Metropolitan Recife. In conclusion,
      monitoring of infant growth has not been effectively consolidated in the State of
      Pernambuco.

PMID- 18327456
TI  - [Forum: rationing health care services. Introduction].
AB  - Explicit rationing of health care is one of the most important issues under
      debate in the academic and political fields in both developed and developing
      countries. The articles presented in this Forum provide an approach to some of
      the questions relating to this issue. The approach is multidisciplinary, covering
      complex ethical questions and the contribution of economics to the debate. The
      analyses reveal specificities associated with the shift from implicit approach
      for rationing of health care, traditionally dominant in health systems, to a
      systematic and explicit priority-setting method in general and the potential
      incompatibility between efficiency and equity objectives in health policy in
      particular. The Forum's reflections link directly to current worldwide
      discussions on the questions "Why ration health care?" and "How to ration health
      care?"

PMID- 18327457
TI  - [Rationing health care services: an inherent issue].
AB  - Limited resources in the health sector force a process of choice between
      alternative health care programs and services and patients or groups of patients
      who will receive care. In the absence of a price mechanism, the priority-setting
      process serves to allocate scarce resources among competing uses, and is thus a
      form of rationing. Traditionally, implicit approaches have dominated the health
      sector's decision-making, mostly by physicians. However, in the face of
      increasing budget constraints and rising patient expectations, more explicit and
      socially acceptable priority-setting practices are needed. Internationally, the
      development of explicit prioritization has proven difficult and controversial.

PMID- 18327458
TI  - [Bioethics reflection on prioritization and rationing of health care: between
      social utility and equity].
AB  - Since health needs outweigh the available resources, choices are imperative. It
      is thus necessary to set limits, criteria, and standards in order to prioritize
      the supply, the recipients, and the services to be provided. Ethical alternatives
      are discussed for the prioritization and rationing of health care, focusing on
      the principles of equity and social utility.

PMID- 18327459
TI  - [Rationing through waiting lists: measuring improvement and possible
      implications].
AB  - This paper analyzes the main policy initiatives for improving waiting lists in
      health care. The authors begin by describing strategies to reduce either waiting
      time or length of the list. They distinguish between demand-side and supply-side
      strategies. They proceed to discuss policies for improving the "quality" of
      waiting time. For each policy, they present both the expected effect and the
      indirect effects that can reduce its effectiveness for improving waiting list
      conditions.

PMID- 18327460
TI  - [Forum: rationing health care services. Postscript].

PMID- 18327461
TI  - Noninvasive means of diagnosing liver fibrosis in hepatitis C.

PMID- 18327462
TI  - Therapeutic approach to acute hepatitis C.

PMID- 18327463
TI  - HIV/AIDS treatment and physicochemical quality control of medicines: evaluation
      of non-generic lamivudine + zidovudine tablets manufactured in Brazil.
AB  - In this work it was evaluated the physicochemical quality of lamivudine +
      zidovudine tablets, whose association belongs to the list of drugs distributed by
      the Brazil's National Program on Sexually Transmitted Diseases and AIDS. Four non
      generic products (lamivudine + zidovudine tablets) were analyzed. They were
      obtained from different Brazilian manufacturers, besides a reference product. The
      quality was evaluated by physicochemical tests described in the official codes. A
      validated reversed-phase high performance liquid chromatography (HPLC) method was
      used for the assay of the active substances. All samples were in accordance to
      the requisites in relation to their physicochemical characteristics. Dissolution
      studies showed similar drug percentual dissolved among all samples. The results
      reflect the interest of the national pharmaceutical industry to ensure the
      delivery of safer and cheaper drugs to the Brazilian people, with particular
      importance in the National Program on Sexually Transmitted Diseases and AIDS.

PMID- 18327464
TI  - Nevirapine-induced side effects in pregnant women: experience of a Brazilian
      university hospital.
AB  - Nevirapine-based therapy is associated with increased frequency of adverse events
      among HIV-infected pregnant women. The aim of this article was to evaluate the
      incidence of adverse effects in HIV-infected women who started nevirapine during
      pregnancy. A retrospective study was performed in our center between January 2003
      and December 2006 analyzing all women prescribed nevirapine during pregnancy.
      Women presenting any risk factor for hepatotoxicity were excluded from the
      analysis. Patients were divided into two groups according to the presence or
      absence of adverse effects, and a correlation to CD4 counts was performed. Liver
      function abnormality was graded according to the Division of AIDS toxicity
      guidelines. A total of 170 women initiated nevirapine during pregnancy, but only
      133 were included in the study. Twenty-seven women (20.3%) presented adverse
      effects, skin rash accounting for 77.8% (21/27 women) and liver function
      abnormalities for 22.2% (6/27) of the cases. Baseline CD4 counts, viral loads and
      transaminases were similar in both groups. All nevirapine side effects were
      developed in less than seven weeks. Four of 31 women with CD4 counts <250
      cells/microL (12.9%) and 23 of 102 women with CD4 counts > or = 250 cells/microL
      (22.5%) developed adverse events. All patients who experienced hepatotoxicity had
      pretreatment CD4 counts > or =250 cells/microL. The incidence of adverse events
      with nevirapine in our study was high, but most of them were cutaneous. There was
      no correlation between high CD4 counts and adverse events when analyzing both
      cutaneous and hepatic reactions; nevertheless, hepatotoxicity occurred only in
      pregnant women with CD4 counts > or =250 cells/microL.

PMID- 18327465
TI  - Induced sputum versus bronchoalveolar lavage in the diagnosis of pneumocystis
      jiroveci pneumonia in human immunodeficiency virus-positive patients.
AB  - Induced sputum is a useful technique for assessing airway inflammation, but its
      role in the diagnosis of lung disease in immunosuppressed patients needs further
      investigation. This study compared the use of induced sputum and BAL in the
      diagnosis of pneumocystosis, in HIV patients. From January 1, 2001, to December
      30, 2002, HIV-positive patients older than 14 were evaluated at a hospital in
      Florianopolis, Santa Catarina, Brazil. Patients with respiratory symptoms for
      seven days or longer, with a normal or abnormal chest X-ray, and those without
      respiratory symptoms but with an abnormal chest X-ray, were included in the
      study. All patients were submitted to clinical, radiological and laboratory
      evaluation, after which induced sputum and bronchoscopy with bronchoalveolar
      lavage were carried out. The samples were subjected to the following techniques:
      Gram and Ziehl-Neelsen staining, quantitative culture growth for pyogenic
      bacteria, direct staining for fungi, culture growth for mycobacteria and fungi,
      and Grocott-Gomori staining for Pneumocystis jiroveci, as well as total and
      differential cell counts. The samples with P. jiroveci were selected, as well as
      the samples for which no etiologic agents were observed. Forty-five patients with
      a mean age of 34.6, 38 male and 40 Caucasian, comprised the subjects.
      Interstitial infiltrate was the most frequent radiological pattern (53.3%). The
      induced sputum sensitivity was 58.8%, specificity 81.8%, predictive positive
      value 90.9%, predictive negative value 39.1% and accuracy 64.4%, for the
      diagnosis of pneumocystosis, compared with BAL. Based on these data, induced
      sputum is a useful technique for the diagnosis of pneumocystosis in HIV patients.

PMID- 18327466
TI  - Using pegylated interferon alfa-2b and ribavirin to treat chronic hepatitis
      patients infected with hepatitis c virus genotype 1: are nonresponders and
      relapsers different populations?
AB  - The combination of pegylated interferon (PEG-INF) and ribavirin is currently the
      best treatment for chronic hepatitis C, providing a sustained virological
      response (SVR) in 54%-63% of patients. In patients infected with hepatitis C
      virus (HCV) genotype 1, the SVR rate is 42%-52%. To evaluate the treatment
      efficacy of this drug combination, we conducted an open, prospective study of 58
      consecutive treatment-naive patients infected with HCV genotype 1 and treated at
      a university hospital, comparing those presenting an SVR (SVRs), nonresponders
      (NRs), and relapsers (RELs). Among the intent-to-treat patients, an end-of
      treatment virological response was achieved in 69% of the sample as a whole and
      in 52% of the SVRs. We found that being an SVR was significantly associated with
      mild fibrosis (p = 0.04) and with undetectable HCV RNA at weeks 12 and 24 of
      treatment (p < 0.0001). Comparing the SVR and REL groups, we observed that being
      older than 40 was significantly associated with being a REL (p = 0.04). Being an
      NR was found to be associated with severe fibrosis and moderate inflammatory
      infiltrates (portal or periportal). In the polytomous logistic regression, no
      independent factors were associated with the REL group when compared with the SVR
      group. We conclude that RELs and NRs differ in comparison with SVRs. The RELs
      accounted for 17% of the sample. The HCV RNA test results at weeks 12 and 24 of
      treatment, although independent predictors of non-response (OR: 4.8 and 8.2,
      respectively), did not differ between SVRs and RELs.

PMID- 18327467
TI  - Assessing risk behaviors and prevalence of sexually transmitted and blood-borne
      infections among female crack cocaine users inSalvador--Bahia, Brazil.
AB  - Crack cocaine use is associated with risky sexual behaviors and sexually
      transmitted infections (STIs), including HIV. We investigated sociodemographic
      and behavioral characteristics and infection rates in female crack cocaine users
      from impoverished communities of Salvador, Bahia, Brazil. A sample of 125 female
      crack cocaine users was recruited. Overall, the interviewees had low educational
      level and high rate of unemployment (close to 90%). One-third (37%) reported
      having traded sex for money or drugs, and 58% reported that they had not used
      condoms during intercourse in the last 30 days. The prevalence of infections was
      low: HIV-1.6%; HCV-2.4%; HBV- 0.8%; HTLV I/II-4.0%; and syphilis-4.0%. The
      combination of dire poverty and high prevalence of risk behaviors turn such
      populations a preferential target of initiatives aiming to reduce drug-related
      harm and promote social development. Low infection rates should not be viewed
      with complacency, but as a window of opportunity to implement prevention
      initiatives and reduce social marginalization.

PMID- 18327468
TI  - Health care-related infections in solid organ transplants.
AB  - The health care-related infections are well-known in a critical care setting, but
      reports of those infections in solid organ transplanted patients are scarce. We
      developed a study of retrospective cohort in a tertiary teaching hospital for 14
      months. Eighty-one patients underwent solid organ transplants. The global
      incidence of health care-related infection was 42.0%. Fifteen percent of the
      cases were occurrences of surgical site infections, 14.0% pneumonias, 9.0%
      primary blood stream infections, 4.0% urinary tract infections and 2.0% skin
      infection. The most prevalent etiologic agents were K. pneumoniae (8.6%), P.
      aeruginosa (7.4%); A. baumannii (5.0%) and S. aureus (2.5%). Mortality was 18.0%,
      none of then related to health care infections. The high rate of those
      infections, mainly surgical site infections, suggests a demand for stricter
      measures to prevent and control health care-related infections.

PMID- 18327469
TI  - Incidence of diarrhea: poor parental recall ability.
AB  - Several methodological issues may have an impact on the incidence rates of
      childhood acute diarrhea reported by community-based studies. This study was
      performed to assess the impact of parental recall ability and definition of
      diarrhea on the estimate of incidence of acute diarrhea. Eighty-four children
      younger than 40 months were randomly selected and visited every other day for
      four weeks and the occurrence of diarrhea was registered. On the last day of the
      study, another visit was performed and the informants were inquired about the
      occurrence of diarrhea during the previous four weeks. Data gathered during the
      four weeks were compared to those obtained on the last visit. Additionally, the
      informants' definition of diarrhea was investigated and compared to the one
      adopted by this study. During the observation period, 33 children suffered
      diarrhea, but only 10 (30.3%) informants reported the occurrence of diarrhea.
      Although 42.4% of those informants reported that their children had been ill over
      that period, they did not report diarrhea. Further, 60.6% children who had
      diarrhea suffered at least one episode in the two weeks prior to the visitation.
      The same definition of diarrhea used in this study was adopted by 52.1% of the
      informants inquired. Parental recall is an unreliable method to estimate the
      incidence of diarrhea and studies with a short interval between the visits should
      be necessary to correctly evaluate this important health problem. Moreover,
      assessing the informants' own definition of diarrhea is a significant
      contribution to the interpretation of the results.

PMID- 18327470
TI  - Multidrug-resistant urinary tract isolates of escherichia coli from Ribeirao
      Preto, Sao Paulo, Brazil.
AB  - Multiple resistances to antimicrobial drugs arising in Escherichia coli isolates
      may complicate therapeutic management of urinary tract infection (UTI) by this
      organism. In order to assess the multidrug resistance (MDR) among urinary E. coli
      isolates, we have tested 11 antimicrobial drugs against 67 isolates from
      outpatients attended in a tertiary-care teaching hospital and of 78 isolates from
      a municipal health unit, respectively in Ribeirao Preto, State of Sao Paulo,
      Brazil. Seventy-six percent and 22% of the isolates from the tertiary-care
      hospital and the municipal unit, respectively, were resistant to three or more
      different classes of agents, and were considered to present MDR. Among the
      isolates from the hospital patients, 73.0%, 65.0%, 58.0%, 58.0% and 31.0% were
      resistant to tetracycline, ampicillin, cephalothin, trimethoprim-sulfamethoxazole
      (TMP/SMX) and norfloxacin, respectively; resistance from the municipal unit
      patients were 31.0%, 37.0%, 8.0%, 29.0% and 12.0% respectively, to the same
      drugs. The predominant phenotype among the MDR isolates presented is ampicillin,
      TMP/SMX and tetracycline resistance. The high prevalence of drug resistance among
      UTI patients calls for continuous surveillance to assure effective control of
      this infection.

PMID- 18327471
TI  - A review of the epidemiology, prevention and treatment of human immunodeficiency
      virus infection in Nigeria.
AB  - In order to amalgamate research findings on HIV/AIDS in Nigeria as well as the
      trend of the infection in a concise manner, we reviewed published articles on the
      HIV/AIDS situation in Nigeria. We categorized this review into several
      subheadings. The HIV prevalence rate has continued to rise steadily from less
      than 0.1% in 1987, to 5.8% in 2001, with a slight decrease in 2003 to 5.0%.
      Although the knowledge about HIV and its mode of transmission is widespread, it
      is however disheartening to note that this did not result into appreciable
      attitudinal change and behavior modification among Nigerians. Both HIV-1 and HIV
      2 have been identified in Nigeria, with HIV-1 being the predominant type.
      Furthermore, several subtypes like subtypes A, B, C, G and J have been identified
      in Nigeria, with several recombinant forms like the CRF02_AG; the major ones
      being A, G and CRF02_AG. HIV-infected patients in Nigeria are also co-infected
      with other viral and bacterial infections, the commonly reported ones being co
      infections with hepatitis B and C. Although treatment of infected patients has
      increased recently, more effort is needed, especially in the area of patients
      monitoring, to maximize the benefits of ART in Nigeria. Finally, Nigeria has made
      appreciable efforts in vaccine development and candidate HIV DNA vaccines have
      been developed utilizing the sequences from predominant subtypes, and these
      candidates have been shown to be immunogenic in animal models. It is therefore
      clear that only the integration of prevention and antiretroviral research
      programmes into a coherent programme that is needed to address the public health
      needs that HIV/AIDS crisis represents for Nigeria.

PMID- 18327472
TI  - Bartonella native valve endocarditis: the first Brazilian case alive and well.
AB  - Bartonella is an important cause of blood culture-negative endocarditis in recent
      studies. Seroprevalence studies in the States of Minas Gerais and Rio de Janeiro
      have shown Bartonella IgG positivity around 14% in healthy adults and 40% in HIV
      seropositive adults, respectively. A case report of a 46-year-old white male with
      moderate aortic regurgitation (AR) due to rheumatic heart disease (RHD), admitted
      due to worsening heart failure, is presented. Clinical features were apyrexia,
      anemia, polyclonal hypergammaglobulinemia, hematuria and splenomegaly. He was
      submitted to surgery due to worsening AR. Histopathology of the excised valve
      showed active bacterial endocarditis and underlying RHD. Routine blood cultures
      were negative. Indirect immunofluorescence (IFI) assays for Coxiella burnetii
      were non-reactive. Bartonella henselae IgG titer was 1:4096 prior to antibiotics
      and 1:512 14 months after treatment. History of close contact with a young cat
      during the months preceding his admission was elicited.

PMID- 18327473
TI  - Infectious keratitis secondary to Histoplasma capsulatum: the first case reports
      in humans.
AB  - The authors report an unusual case of fungal keratitis caused by Histoplasma
      capsulatum in a male immunocompetent patient. PCR confirmed the presence of the
      fungus DNA in the material studied. To our knowledge this is the first reported
      case in humans described all over the world.

PMID- 18327474
TI  - Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the
      amazon rainforest.
AB  - Neisseria meningitidis has not been seen as a significant cause of infectious
      haemorrhagic fever in the Amazon inlands; most reported cases are from the city
      of Manaus, the capital of the State of Amazonas. This picture is sustained by the
      lack of reliable microbiology laboratories, the perception of the health care
      workers, and the difficult to reach medical assistance; thus the number of
      confirmed cases is even lower with no reference of the strains phenotype. We
      report here the investigation of a case of suspected meningococcemia and his
      close contacts in a rural community in the Coari Lake, up the Amazon River.

PMID- 18327475
TI  - Meningitis caused by Alcaligenes xylosoxidans in a patient with HIV/AIDS.
AB  - The purpose of the present work was to inform about the first case of meningitis
      associated to the bacteria Alcaligenes xylosoxidans in a patient with HIV/AIDS.
      The patient was a 46-year-old male, with the antecedent of have been diagnosed
      for HIV/ AIDS, who attended in the Hospital Universitario de Colima, Mexico, with
      fever, shock and meningismus. The study of the cerebrospinal fluid showed
      pleocytosis, elevated protein levels and hypoglycorrhachia. The culture yielded
      the presence of Alcaligenes xylosoxidans with sensitivity to ciprofloxacin. After
      14 days of treatment with this antibiotic, the patient showed neurologic
      improvement and was able to continue with his outpatient antiretroviral
      treatment. The present case shows the importance of the inclusion of this
      bacterium in the differential diagnosis of the neurological infections in
      HIV/AIDS patients and emphasizes the importance of considering the bacterial
      meningitis in this population.

PMID- 18327476
TI  - Recurring Candida albicans esophagitis in a HIV-infected patient undergoing long
      Term antiretroviral therapy, and with absent-negligible immunodeficiency.
AB  - A patient with HIV infection developed the first episode of AIDS-defining
      opportunism (severe Candida albicans esophagitis) with an underlying CD4+
      lymphocyte count of 1,025 cells/microL. After treatment with a highly active
      antiretroviral therapy (HAART), taken with insufficient compliance and leaving a
      residual viral load, our patient suffered from two relapses of esophageal
      candidiasis, which occurred three months and seven years later, when his CD4+
      lymphocyte count was 930 and 439 cells/microL, respectively, and a viral load
      slightly above 10(4) copies/mL was still present. Also in the HAART era, Candida
      esophagitis remains one of the most common AIDS-defining diseases, but a
      presentation with a concurrent CD4+ count above 1,000 cells/microL remains a rare
      exception, as well as the two isolated, subsequent relapses, occurred with a CD4+
      count ranging from 439 to 930 cells/microL, and a residual HIV viremia due to
      insufficient adherence to the prescribed HAART regimens. Our case report
      represents the opportunity to revisit the epidemiology and, especially, the
      pathogenesis of this opportunistic fungal complication in HIV-infected patients
      and in other subjects at risk, on the ground of an extensive literature review,
      and to explore possible alternative supporting factors other than the crude
      absolute CD4+ lymphocyte count, with emphasis on the possible role of a
      persisting HIV viremia, and other potential contributing factors. Clinicians
      engaged with immunocompromised patients and subjects with HIV disease, should be
      aware that a Candida esophagitis may occur and relapse also when the cell
      mediated immunity, as measured by a simple CD4+ cell count, do not show relevant
      abnormalities.

PMID- 18327477
TI  - Congenital toxoplasmosis infection in an infant born to an HIV-1-infected mother.
AB  - We report the occurrence of congenital toxoplasmosis in an infant born to an HIV
      infected mother who had high anti-toxoplasma IgG and negative IgM at nine weeks
      of gestation. We briefly review available literature and discuss the possible
      mechanisms of transmission of congenital toxoplasmosis among HIV infected
      pregnant women.

PMID- 18327478
TI  - Dermatophyte susceptibilities to antifungal azole agents tested in vitro by broth
      macro and microdilution methods.
AB  - The in vitro susceptibility of dermatophytes to the azole antifungals
      itraconazole, fluconazole and ketoconazole was evaluated by broth macro and
      microdilution methods, according to recommendations of the CLSI, with some
      adaptations. Twenty nail and skin clinical isolates, four of Trichophyton
      mentagrophytes and 16 of T. rubrum were selected for the tests. Itraconazole
      minimal inhibitory concentrations (MIC) varied from < 0.03 to 0.25 microg/mL in
      the macrodilution and from < 0.03 to 0.5 microg/mL in the microdilution methods;
      for fluconazole, MICs were in the ranges of 0.5 to 64 microg/mL and 0.125 to 16
      microg/mL by the macro and microdilution methods, respectively, and from < 0.03
      to 0.5 microg/mL by both methods for ketoconazole. Levels of agreement between
      the two methods (+/- one dilution) were 70% for itraconazole, 45% for fluconazole
      and 85% for ketoconazole. It is concluded that the strains selected were
      inhibited by relatively low concentrations of the antifungals tested and that the
      two methodologies are in good agreement especially for itraconazole and
      ketoconazole.

PMID- 18327480
TI  - Comparison between E-test and CLSI broth microdilution method for antifungal
      susceptibility testing of Candida albicans oral isolates.
AB  - Thirty Candida albicans isolated from oral candidosis patients and 30 C. albicans
      isolated from control individuals were studied. In vitro susceptibility tests
      were performed for amphotericin B, fluconazole, 5-flucytosine and itraconazole
      through the Clinical and Laboratorial Standards Institute (CLSI) reference method
      and E test system. The results obtained were analyzed and compared. MIC values
      were similar for the strains isolated from oral candidosis patients and control
      individuals. The agreement rate for the two methods was 66.67% for amphotericin
      B, 53.33% for fluconazole, 65% for flucytosine and 45% for itraconazole.
      According to our data, E test method could be an alternative to trial routine
      susceptibility testing due to its simplicity. However, it can not be considered a
      substitute for the CLSI reference method.

PMID- 18327481
TI  - Antibacterial activity of GUAVA, Psidium guajava Linnaeus, leaf extracts on
      diarrhea-causing enteric bacteria isolated from Seabob shrimp, Xiphopenaeus
      kroyeri (Heller).
AB  - Guava leaf tea of Psidium guajava Linnaeus is commonly used as a medicine against
      gastroenteritis and child diarrhea by those who cannot afford or do not have
      access to antibiotics. This study screened the antimicrobial effect of essential
      oils and methanol, hexane, ethyl acetate extracts from guava leaves. The extracts
      were tested against diarrhea-causing bacteria: Staphylococcus aureus, Salmonella
      spp. and Escherichia coli. Strains that were screened included isolates from
      seabob shrimp, Xiphopenaeus kroyeri (Heller) and laboratory-type strains. Of the
      bacteria tested, Staphylococcus aureus strains were most inhibited by the
      extracts. The methanol extract showed greatest bacterial inhibition. No
      statistically significant differences were observed between the tested extract
      concentrations and their effect. The essential oil extract showed inhibitory
      activity against S. aureus and Salmonella spp. The strains isolated from the
      shrimp showed some resistance to commercially available antibiotics. These data
      support the use of guava leaf-made medicines in diarrhea cases where access to
      commercial antibiotics is restricted. In conclusion, guava leaf extracts and
      essential oil are very active against S. aureus, thus making up important
      potential sources of new antimicrobial compounds.

PMID- 18327482
TI  - Seroprevalence of Toxoplasma gondii infection among indian people living in
      Iauarete, Sao Gabriel da Cachoeira, Amazonas, Brazil.
AB  - The goal of this survey was to estimate the seroprevalence of Toxoplasma gondii
      infection in Iauarete, a multiethnic Indian community in the upper Rio Negro
      basin. We carried out a cross-sectional survey (n = 260), in order to obtain
      serum samples and demographic data. The sample was randomly selected, by family
      conglomerate analysis. Serodiagnosis was performed by an enzyme-linked
      immunosorbent assay and indirect immunofluorescence. Prevalence of reactivity was
      73.5% (191/260), being higher in the older-age groups, reaching 95.7% (44/46) in
      the group aged 50 years or more. The majority of seropositive subjects had titers
      equal to or less than 1:64. Seroprevalence was greater in Indians belonging to
      the Hupda ethnic group (p = 0.03). According to the present survey, Indian people
      living in Iauarete have a high prevalence of antibodies to T. gondii. Demographic
      concentration and urbanization within low sanitation and poor hygiene
      backgrounds, as well as unfiltered water consumption, may be related to the high
      frequency of T. gondii seroprevalence observed in the studied area.

PMID- 18327483
TI  - Febrifugine derivative antimalarial activity: quantum mechanical predictors.
AB  - Plasmodium falciparum resistant strain development has encouraged the search for
      new antimalarial drugs. Febrifugine is a natural substance with high activity
      against P. falciparum presenting strong emetic property and liver toxicity, which
      prevent it from being used as a clinical drug. The search for analogues that
      could have a better clinical performance is a current topic. We aim to
      investigate the theoretical electronic structure by means of febrifugine
      derivative family semi-empirical molecular orbital calculations, seeking the
      electronic indexes that could help the design of new efficient derivatives. The
      theoretical results show there is a clustering in well-defined ranges of several
      electronic indexes of the most selective molecules. The model proposed for
      achieving high selectivity was tested with success.

PMID- 18327484
TI  - The effect of antioxidant properties of aqueous garlic extract and Nigella sativa
      as anti-schistosomiasis agents in mice.
AB  - The aim of this study was to assess the antioxidant and anti-schistosomal
      activities of the garlic extract (AGE) and Nigella sativa oil (NSO) on normal and
      Schistosoma mansoni-infected mice. AGE (125 mg kg-1, i.p.) and NSO (0.2 mg kg-1,
      i.p.) were administrated separately or in combination for successive 28 days,
      starting from the 1st day post infection (pi). All mice were sacrificed at weeks
      7 pi. Hematological and biochemical parameters including liver and kidney
      functions were measured to assess the progress of anemia, and the possibility of
      the tissue damage. Serum total protein level, albumin, globulin and cholesterol
      were also determined. Malondialdehyde (MDA) and glutathione (GSH) levels were
      determined in the liver tissues as biomarkers for oxidative and reducing status,
      respectively. The possible effect of the treatment regimens on Schistosoma worms
      was evaluated by recording percentage of the recovered worms, tissue egg and
      oogram pattern. Result showed that, protection with AGE and NSO prevented most of
      the hematological and biochemical changes and markedly improved the antioxidant
      capacity of schistosomiasis mice compared to the infected-untreated ones. In
      addition, remarkable reduction in worms, tissue eggs and alteration in oogram
      pattern were recorded in all the treated groups. The antioxidant and
      antischistosomal action of AGE and NSO was greatly diverse according to treatment
      regimens. These data point to these compounds as promising agents to complement
      schistosomiasis specific treatment.

PMID- 18327485
TI  - Comparison of direct immunofluorescence, conventional cell culture and polymerase
      chain reaction techniques for detecting respiratory syncytial virus in
      nasopharyngeal aspirates from infants.
AB  - A total of 316 samples of nasopharyngeal aspirate from infants up to two years of
      age with acute respiratory-tract illnesses were processed for detection of
      respiratory syncytial virus (RSV) using three different techniques: viral
      isolation, direct immunofluorescence, and PCR. Of the samples, 36 (11.4%) were
      positive for RSV, considering the three techniques. PCR was the most sensitive
      technique, providing positive findings in 35/316 (11.1%) of the samples, followed
      by direct immunofluorescence (25/316, 7.9%) and viral isolation (20/315, 6.3%) (p
      < 0.001). A sample was positive by immunofluorescence and negative by PCR, and 11
      (31.4%) were positive only by RT-PCR. We conclude that RT-PCR is more sensitive
      than IF and viral isolation to detect RSV in nasopharyngeal aspirate specimens in
      newborn and infants.

PMID- 18327486
TI  - Influenza virus and proteolytic bacteria co-infection in respiratory tract from
      individuals presenting respiratory manifestations.
AB  - A role for proteolytic bacteria in the exacerbation of influenza virus has been
      shown in natural hosts such as pigs and humans. Four hundred seven samples were
      collected from the respiratory tract of individuals presenting clinical
      manifestations, during influenza season (2003-2005) in Sao Paulo City. The aim of
      this study was to evaluate the incidence of determined bacteria co-infecting
      virus in human respiratory tract. Tests, such as bacteriological,
      immunofluorescence (IF), RT/PCR and hemagglutination (HA) were used for bacterial
      and viral investigation. Thirty seven (9.09%) positive for influenza virus were
      screened by IF. The RT/PCR confirmed the presence of influenza virus in these
      samples. Bacterial and agar casein tests demonstrated that 18 (48.64%)
      individuals were infected with proteolytic bacteria such as Staphylococcus spp.,
      Streptococcus spp. and Pseudomonas spp. Among these samples, 13 (35.13%) were co
      infected with influenza A virus. Influenza type B, co-infecting bacteria were
      found in five (13.51%) samples. In vitro the S. aureus protease increased the
      influenza HA titer after contact for 30 min at 25 masculineC. Results revealed
      the occurrence of co-infection with proteolytic bacteria and influenza in the
      evaluated individuals. This finding corroborates that virus versus bacteria
      synergism could be able to potentiate respiratory infection, increasing damage to
      hosts.

PMID- 18327487
TI  - Paracoccidioidomycosis: infiltrated, sarcoid-like cutaneous lesions
      misinterpreted as tuberculoid leprosy.
AB  - The authors report a case of paracoccidioidomycosis misinterpreted as tuberculoid
      leprosy, both on clinical and histological examination. Sarcoid-like cutaneous
      lesion as the initial presentation is rare in young patient with
      paracoccidioidomycosis and can simulate other infectious or inflammatory
      diseases. On histology, tuberculoid granuloma presented similar difficulties.
      Treatment with dapsone, a sulfonamide derivative, could have delayed the presumed
      natural clinical course to the classical juvenile type of paracoccidioidomycosis,
      observed only 24 months after the patient had been treated for leprosy.

PMID- 18327488
TI  - Cutaneous infection caused by Corynebacterium pseudodiphtheriticum: a
      microbiological report.
AB  - We report here a rare case of cutaneous infection due to Corynebacterium
      pseudodiphtheriticum. The patient presented to the clinical laboratory with a
      skin ulcer on his left leg. Gram-stained preparation of the purulent secretion
      revealed the presence of numerous rod-shaped Gram-positive organisms in the
      absence of any other species. The organism was grown in pure culture on sheep
      blood agar and was further identified as C. pseudodiphtheriticum using a
      commercial identification system (API-Coryne, BioMerieux, France). The infection
      was successfully treated with ciprofloxacin. This case emphasizes the importance
      of the clinical microbiology laboratory in correctly identifying Gram-positive
      organisms obtained in pure culture from skin ulcers.

PMID- 18327489
TI  - Cystic echinococcosis in southern Brazil.
AB  - Cystic echinococcosis (CE) is very common in the southern part of Rio Grande do
      Sul State where sheep and cattle raising is the most important economical
      activity. Prevalence in intermediate hosts is well known due to reports in
      slaughterhouses while human reports are of discussed value. This is due to
      underreporting of cases and few epidemiological studies make it difficult to
      assess the situation of echinococcosis in the population. Whereas cattle
      infection rate is more or less stable around 12% of the slaughter animals, in
      sheep there has been an increasing number in the last five years. Some efforts
      have been done to control the zoonosis but no effective results were obtained so
      far. Probably educational efforts to change human practices (feeding dogs with
      raw viscera), periodic treatment of dogs with praziquantel and joined actions
      with slaughterhouses could bring more attention to improve some control measures.

PMID- 18327490
TI  - Prevalence of intestinal parasites in children from public daycare centers in the
      city of Belo Horizonte, Minas Gerais, Brazil.
AB  - The objective of this study was to verify the occurrence of intestinal parasites
      in 3 to 6-year-old children from daycare centers maintained by the municipal
      government of Belo Horizonte, Minas Gerais, Brazil. Coproparasitological tests
      performed in 472 children have shown that 24.6% of them had some type of
      parasites, 6.6% of the children having more than one type. Among protozoa,
      Entamoeba coli (14.0%) and G. duodenalis (9.5%) were the most prevalent, whereas
      Ascaris lumbricoides (3.0%) and Trichuris trichiura (1.1%) were the most frequent
      among the helminths. Thus, we can observe that intestinal parasites still
      represent a serious public health problem in Belo Horizonte, especially among
      children and in areas where the socioeconomic conditions are less favorable.

PMID- 18327491
TI  - Optimization of the Sybr Green real time PCR for the detection of Human Herpes
      Virus type 6 (HHV-6).
AB  - HHV-6 is the etiological agent of Exanthem subitum which is considered the sixth
      most frequent disease in infancy. In immuno-compromised hosts, reactivation of
      latent HHV-6 infection may cause severe acute disease. We developed a Sybr Green
      Real Time PCR for HHV-6 and compared the results with nested conventional PCR. A
      214 pb PCR derived fragment was cloned using pGEM-T easy from Promega system.
      Subsequently, serial dilutions were made in a pool of negative leucocytes from 10
      6 ng/microL (equivalent to 2465.8 molecules/microL) to 10-9 (equivalent to 2.46
      molecules/microL). Dilutions of the plasmid were amplified by Sybr Green Real
      Time PCR, using primers HHV3 (5' TTG TGC GGG TCC GTT CCC ATC ATA 3)'and HHV4 (5'
      TCG GGA TAG AAA AAC CTA ATC CCT 3') and by conventional nested PCR using primers
      HHV1 (outer): 5'CAA TGC TTT TCT AGC CGC CTC TTC 3'; HHV2 (outer): 5' ACA TCT ATA
      ATT TTA GAC GAT CCC 3'; HHV3 (inner) and HHV4 (inner) 3'. The detection threshold
      was determined by plasmid serial dilutions. Threshold for Sybr Green real time
      PCR was 24.6 molecules/microL and for the nested PCR was 2.46 molecules/microL.
      We chose the Real Time PCR for diagnosing and quantifying HHV-6 DNA from samples
      using the new Sybr Green chemistry due to its sensitivity and lower risk of
      contamination.

PMID- 18327492
TI  - Reactivation of Trypanosoma cruzi infection in immunosuppressed patients:
      contributions for the laboratorial diagnosis standardization.

PMID- 18327493
TI  - [Blood alcohol concentration in fatal traffic accidents in the Federal District,
      Brazil].
AB  - The objective of the study was to assess the association between high blood
      alcohol levels and fatal victims of traffic accidents in the Brazilian Federal
      District, in 2005. A total of 442 casualties (163 pedestrians, 84 victims of
      overturns, and 195 of collisions) were studied. Blood alcohol concentration was
      analyzed in 238 cases (53.7%). Most victims were young males, aged between 18 and
      35 years. Blood alcohol levels higher than 0.6 g/L were detected in 44.2% of
      collision victims; 57.7% of victims of overturns and 32.5% of pedestrians. The
      difference in proportions between overturn victims with blood alcohol
      concentration higher than 0.6 g/L and those victims of other traffic accidents
      was statistically significant.

PMID- 18327494
TI  - [Approach on smoking cessation by training public health providers].
AB  - The study evaluated the results of a smoking cessation training program including
      40 public health providers from November 2004 to March 2007. A total of 3,419
      smokers received minimum individual intervention and 982 had group intervention.
      Of all, 9.2% quit smoking. The main difficulties for smoking cessation reported
      by health providers were: low patient compliance (11%); lack of medications
      (38%); and lack of health unit infrastructure/support (29%). The training allowed
      to reaching out a larger population through smoking cessation approaches at
      health units.

PMID- 18327495
TI  - [Right to health litigations: a discussion on the observance of the principles of
      Brazil's Health System].
AB  - The paper reflects upon the legal interpretations of the right to health and its
      consequences. In order to exemplify the complexity of the theme and its emotional
      appeal, it analyzes the Supreme Court's decision in a public litigation against
      the State of Alagoas demanding that medication be supplied. Different
      interpretations, by both judges and health professionals, of the notion of
      integral health care, one of the principles of Brazil's Health System, are
      examined. It is held that scarcity of resources must be taken into consideration
      when drawing up public policies that aim to allocate funding efficiently and in a
      manner that is compatible with the principals of the health system. Finally, the
      impact of judicial decisions concerning medication not offered by the system and
      the behavior of the Brazilian judiciary with this respect are discussed.

PMID- 18327496
TI  - [Sugar cane burning in Brazil: respiratory health effects].
AB  - The article aimed to update scientific literature information about respiratory
      health effects caused by sugarcane burning, considering the expansion of
      sugarcane plantations in Brazil and in the state of Sao Paulo. Articles published
      between 1996 and 2006, which deal with the health effects of sugarcane burning
      and/or air pollutants originating from this burning, were discussed. These
      studies suggest that part of the population--especially the elderly, children and
      asthmatics--suffers health effects of sugarcane burning. As a result, these
      people require health care, thus affecting health services and their families.

PMID- 18327497
TI  - Agreement between data obtained from repeated interviews with a six-years
      interval.
AB  - The objective of the study was to compare information collected through face-to
      face interviews at first time and six years later in a city of Southeastern
      Brazil. In 1998, 32 mothers (N=32) of children aged 20 to 30 months answered a
      face-to-face interview with structured questions regarding their children's
      brushing habits. Six years later this same interview was repeated with the same
      mothers. Both interviews were compared for overall agreement, kappa and weighted
      kappa. Overall agreement between both interviews varied from 41 to 96%. Kappa
      values ranged from 0.00 to 0.65 (very bad to good) without any significant
      differences. The results showed lack of agreement when the same interview is
      conducted six years later, showing that the recall bias can be a methodological
      problem of interviews.

PMID- 18327498
TI  - [Physical activity and mental health status among elderly people].
AB  - OBJECTIVE: To evaluate the association between physical activity level and mental
      health status among elderly people. METHODS: This was a population-based survey
      with a probabilistic sample of 875 elderly people from a city of Southern Brazil,
      in 2002. The International Physical Activity Questionnaire and the Brazil Old Age
      Schedule questionnaire were applied. The mental health problems evaluated were
      depressions and dementia. Total physical activity (leisure-time, occupation,
      transportation and housework). After descriptive and bivariate analyses, adjusted
      analyses were performed by means of logistic regression, with adjustment for the
      factors of total physical activity, leisure-time activity and depression and
      dementia scores. RESULTS: There were statistically significant inverse
      associations between dementia and depression with total physical activity and
      leisure-time physical activity. The odds ratio for total physical activity
      adjusted for dementia among sedentary subjects in comparison with active subjects
      was 2.74 (95% CI: 1.85; 4.08), while the respective value adjusted for depression
      was 2.38 (95% CI: 1.70; 3.33). CONCLUSIONS: The results reinforce the importance
      of active lifestyles for preventing mental health problems among elderly people.
      It is inferred that the physical activity was able to reduce and/or delay the
      risks of dementia, although it cannot be stated that dementia is avoided through
      physical activity.

PMID- 18327499
TI  - Knowledge, attitude and practice of mammography among women users of public
      health services.
AB  - OBJECTIVE: To evaluate knowledge, attitude and practice related to mammography
      among women users of local health services, identifying barriers to its
      performance. METHODS: A total of 663 women were interviewed at 13 local health
      centers in a city of Southeastern Brazil, in 2001. Interviewees were randomly
      selected at each center and they were representative from different socioeconomic
      conditions. The number of interviewees at each center was proportional to monthly
      mean appointments. For data analysis, answers were described as knowledge,
      attitude, practice and their respective adequacies and then they were correlated
      with control variables through the chi-square test. RESULTS: Only 7.4% of the
      interviewees had adequate knowledge on mammography, while 97.1% of women had an
      adequate attitude. The same was seen for the practice of mammography that was
      adequate in 35.7% of the cases. The main barrier to mammography was lack of
      referral by physicians working at the health center (81.8%). There was an
      association between adequacy of attitude and five years or more of education and
      being married. There was also an association between adequacy of mammography
      practice and being employed and family income up to four minimum wages.
      CONCLUSIONS: Women users of local health services had no adequate knowledge and
      practice related to mammography despite having an adequate attitude about this
      exam.

PMID- 18327500
TI  - [Socioeconomic differences between self- and interviewer-classification of
      color/race].
AB  - OBJECTIVE: To assess (1) the consistency between self-classified and interviewer
      classified color/race according to socioeconomic and demographic variables and
      (2) the magnitude of the ethnic-racial inequalities of income and socioeconomic
      status using self-classified and interviewer-classified color/race. METHODS: A
      cross-sectional population-based study was carried out among individuals of both
      sexes aged>or=20 years (N=3,353), living in the urban area of a city in Southern
      Brazil, in 2005. A two-stage sampling scheme was adopted and data collection was
      performed at participants' homes. Face-to-face interviews were conducted using
      standardized precoded questionnaires. The consistency between self-classified and
      interviewer-classified color/race was checked by means of concordance proportions
      and kappa statistics. Ethnic-racial inequalities of income and socioeconomic
      status were estimated using linear and ordinal logistic regression models,
      adjusting for sex, age and schooling. RESULTS: The response rate was 93.5%.
      Despite the high reproducibility observed between self-classified and interviewer
      classified color/race, a tendency towards whitening was seen among the
      interviewees. Self-classified brown (pardo) and black individuals were 1.4 and
      1.5 times more likely to be classified as whites than as blacks and browns
      (pardos), respectively. Socioeconomically deprived strata presented higher kappa
      values. Ethnic-racial inequalities of income and socioeconomic status were found,
      and these were slightly greater using interviewer-classified color/race.
      CONCLUSIONS: Racial classification presents a tendency towards the whitening of
      participants by interviewers. Browns (pardos) and blacks were socioeconomically
      disadvantaged in comparison with whites.

PMID- 18327501
TI  - [Vulnerability to HIV/AIDS in married heterosexual people or people in a common
      law marriage].
AB  - OBJECTIVE: To study knowledge, preventive behavior, and perception regarding
      HIV/AIDS of heterosexual men and women that are married or in a common-law
      marriage. METHODS: Exploratory study carried out in the Federal District of
      Brazil, between 2001 and 2002. Heterosexual men and women (N=200) aged 18 and 49,
      married or in a common-law marriage were divided into two groups: (I) 50 couples
      approached in public places, and (II) 100 users of a Basic Health Unit, 50 were
      women and 50 were men. The instrument for data collection was a semi-structured
      questionnaire on demographic, socioeconomic and behavioral characteristics of the
      interviewees, with 38 questions, two of which were open. RESULTS: The age
      distribution between the groups was similar, but group I had a higher level of
      schooling and income, while group II had less knowledge about the ways that HIV
      is transmitted. The use of condoms was equally mentioned by both groups as one of
      the types of prevention. Of the interviewees, 14% reported its regular use in the
      last year. The main reasons for not using condoms were "trusting the partner" and
      "being incompatible with having a fixed partner". The perception of the risk of
      infection was more frequent among women. CONCLUSIONS: The population studied was
      vulnerable to the risk of getting the disease, although the interviewees had
      enough knowledge on HIV/AIDS. Their perceptions of the couple reflected their
      acculturation in relation to gender roles and the hierarchization of the
      affective-sexual relationship, which can contribute to the small adoption of
      preventive behavior.

PMID- 18327502
TI  - [Reliability of the instrument for classifying elderly people's capacity for self
      care].
AB  - OBJECTIVE: To evaluate the reliability of an instrument for classifying elderly
      people regarding their capacity for self-care, which was developed to assist
      occupational therapists in attending elderly people at primary healthcare units.
      METHODS: Stability and internal consistency tests were carried out. To validate
      the instrument, tests were applied to a sample of 30 individuals aged 60 years
      and over, on two occasions. The statistical analysis was performed after careful
      grouping of the responses. This led to the formulation of a simplified version of
      the instrument. The stability of this version was assessed using the kappa
      coefficient and the internal consistency by Cronbach's alpha coefficient.
      RESULTS: The stability ranged from moderate to excellent. The internal
      consistency was checked only for areas that were shown to be appropriate for
      using the methodology, based on calculations of Cronbach's alpha: three of the
      six questions in the "social profile" area and the blocks of basic and
      instrumental activities of daily living in the "functional capacity" area, which
      respectively consisted of nine and eight activities. CONCLUSIONS: Following the
      stability and internal consistency tests, the instrument made it possible to
      succinctly and simply classify elderly people with regard to their functional
      capacity for basic and instrumental activities, and to characterize them
      regarding other aspects of self-care. The evidence regarding its reliability and
      validity could be expanded by means of new studies.

PMID- 18327503
TI  - [Family screening for HBB*S gene and detection of new cases of sickle cell trait
      in Northeastern Brazil].
AB  - OBJECTIVE: To estimate the additional number of affected individuals based on the
      prevalence of sickle-cell syndromes among relatives of index cases. METHODS:
      Cross-sectional study of relatives of a random sample of index cases identified
      through a neonatal screening program in Northeastern Brazil, between 2001 and
      2005. The extended family trial model included 463 relatives of 21 index cases.
      Relatives were classified as nuclear family (NF: father, mother, and siblings);
      first degree extended family (N1: grandparents, uncles and aunts, and first
      cousins); second degree extended family (N2: children of first cousins); extended
      family (NA: NF+N1+N2); and extended nuclear family (NA1: NF+N1). The presence of
      HBB*S and other abnormal hemoglobins was confirmed by high-performance liquid
      chromatography. The association between the presence of HBB*S and other variables
      was calculated using prevalence ratios and their respective 95% confidence
      intervals, and differences between means were calculated using Student's t test
      with a 5% significance level. RESULTS: Of relatives, 81% had no knowledge of
      sickle-cell anemia and HBB*S was present in 114 family members. A total of 53.3%
      of the studied population was considered as of reproductive age, and 80% of HBB*S
      carriers had already had children. Frequency was higher among NF (69%), but was
      also high in N1 (22.8%). NA1 screening resulted in the detection of 69 carriers
      additional (a 172% increase). CONCLUSIONS: These results indicate that family
      screening for the identification of sickle-cell carriers should be extended to
      first degree relatives.

PMID- 18327504
TI  - Aedes aegypti, Aedes albopictus, and dengue in Argentina: current knowledge and
      future directions.
AB  - Since the reinfestation of South American countries by Ae. aegypti, dengue fever
      (DF) and dengue hemorrhagic fever (DHF) have become a major public health
      concern. The aim of this paper was to review the information related with Aedes
      vectors and dengue in Argentina since the reintroduction of Ae. aegypti in 1986.
      The geographic distribution of Ae. albopictus is restricted to the Northeast, and
      that of Ae. aegypti has expanded towards the South and the West in comparison
      with the records during the eradication campaign in the 1960s. Since 1998, 4,718
      DF cases have been reported concentrated in the provinces of Salta, Formosa,
      Misiones, Jujuy and Corrientes. Despite the circulation of three dengue virus
      serotypes (DENV-1, -2 and -3) in the North of the country, DHF has not occurred
      until the present. The information published over the last two decades regarding
      mosquito abundance, temporal variations, habitat characteristics, competition,
      and chemical and biological control, was reviewed. Considering the available
      information, issues pending in Argentina are discussed. The presence of three
      DENV, the potential spread of Ae. albopictus, and the predicted climate change
      suggest that dengue situation will get worse in the region. Research efforts
      should be increased in the Northern provinces, where DHF is currently an actual
      risk.

PMID- 18327505
TI  - Molecular paleoparasitological diagnosis of Ascaris sp. from coprolites: new
      scenery of ascariasis in pre-Colombian South America times.
AB  - Paleoparasitological studies using microscopy showed that Ascarisand Trichuris
      trichiura are the human intestinal parasites most found in archaeological sites.
      However, in pre-Columbian South American archaeological sites, Ascaris is rare.
      In this work we standardized a molecular methodology for Ascaris diagnosis
      directly from ancient DNA retrieved from coprolites. Using cythochrome b gene
      (142 bp) target, ancient DNA sequences were retrieved from South American
      samples, negative by microscopy. Moreover, the methodology applied was sensitive
      enough to detect ancient DNA extracted from 30 Ascaris eggs from an European
      coprolite. These results revealed a new scenery for the paleodistribution of
      Ascaris in South America.

PMID- 18327506
TI  - Individual serological follow-up of patients with suspected or confirmed
      abdominal angiostrongyliasis.
AB  - Abdominal angiostrongyliasis (AA) is a zoonotic nematode infection caused by
      Angiostrongylus costaricensis, with widespread occurrence in the Americas.
      Although the human infection may be highly prevalent, morbidity is low in
      Southern Brazil. Confirmed diagnosis is based on finding parasitic structures in
      pathological examination of biopsies or surgical resections. Serology stands as
      an important diagnostic tool in the less severe courses of the infection. Our
      objective is to describe the follow up of humoral reactivity every 2-4 weeks up
      to one year, in six individuals with confirmed (C) and ten suspected (S) AA.
      Antibody (IgG) detection was performed by ELISA and resulted in gradually
      declining curves of reactivity in nine subjects (56%) (4C + 5S), that were
      consistently negative in only three of them (2C + 1S) after 221, 121 and 298
      days. Three individuals (2C + 1S) presented with low persistent reacitivity,
      other two (1C + 1S) were serologically negative from the beginning, but also
      presenting a declining tendency. The study shows indications that abdominal
      angiostrongyliasis is usually not a persistent infection: although serological
      negativation may take many months, IgG reactivity is usually declining along time
      and serum samples pairing may add valuable information to the diagnostic workout.

PMID- 18327507
TI  - Long-term storage and viability of Ochlerotatus albifasciatus (Diptera:
      Culicidae).
AB  - The viability of Ochlerotatus albifasciatus (Macquart) eggs stored at room
      temperature and at 5 degrees C was studied over 31 months. After 12, 18 and 31
      months of storage, eggs were acclimatized at 22 degrees C for ten days, and then
      inundated twice every seven days. The effect of the storage period on the
      percentage of hatching was analyzed by one way ANOVA. Differences on the hatching
      response between the first and second flooding were analyzed by paired t-test.
      Differences on the hatching response between the two storage conditions were
      analyzed by Mann-Whitney rank test. Results showed that (1) Oc. albifasciatus
      eggs were able to survive and hatch over 31 months; (2) the percent hatching of
      eggs stored at 5 degrees C was higher than that of eggs stored at room
      temperature; and (3) low temperatures and long periods without water favor
      installment hatching.

PMID- 18327508
TI  - Physical activity and cardiovascular health-work and leisure differ.

PMID- 18327509
TI  - Occupational physical activity, energy expenditure and 11-year progression of
      carotid atherosclerosis.
AB  - OBJECTIVES: This study prospectively assessed the effects of occupational
      physical activity on atherosclerosis progression. METHODS: This population-based
      prospective study of ultrasonographically assessed carotid intima media thickness
      (IMT) used repeated measures of occupational physical activity during baseline, 4
      year, and 11-year examinations of 612 Finnish men 42-60 years of age at baseline.
      The association between five measures of energy expenditure and the 11-year
      change in maximum IMT was evaluated in regression models adjusting for 21
      potential confounders, including biological factors, leisure-time physical
      activity, smoking, socioeconomic status, psychosocial job factors, and baseline
      health status. RESULTS: At baseline, 31% of all the men and 51% of those with
      ischemic heart disease (IHD) exceeded the recommended maximum levels of relative
      aerobic strain. All five measures of energy expenditure were significantly
      associated with adjusted 11-year IMT change. Significant interactions were found
      between IHD and several measures of energy expenditure. Maximum relative aerobic
      strain resulted in a 90% increase in IMT among the men with IHD compared with a
      46% increase among those without IHD. The men with preexisting carotid stenosis
      also had higher rates of IMT progression than the men without this condition.
      CONCLUSIONS: This study shows that high energy expenditures at work are
      associated with an accelerated progression of atherosclerosis even after control
      for virtually all known cardiovascular risk factors, especially among older
      workers and workers with preexisting IHD or carotid artery stenosis. The findings
      support the hemodynamic theory of atherosclerosis and have important implications
      for workplace surveillance and disease prevention.

PMID- 18327510
TI  - Shift work, occupational noise and physical workload with ensuing development of
      blood pressure and their joint effect on the risk of coronary heart disease.
AB  - OBJECTIVES: The change in systolic blood pressure (SBP) over an 8-year period was
      explored in groups defined according to exposure to shift work, occupational
      noise, and physical workload. The impact of baseline SBP and its increase in
      relation to coronary heart disease (CHD) risk due to these exposures was also
      studied. METHODS: The study cohorts (N=1288 for CHD follow-up, N=884 for SBP
      follow-up) consisted of industrially employed middle-aged men from the Helsinki
      Heart Study. Shiftwork status was obtained from a questionnaire, and other
      exposures were determined with the Finnish job-exposure matrix. SBP was measured
      in the Helsinki Heart Study, and CHD end points were obtained from official
      Finnish registers. The joint effects of baseline SBP, its change, and the
      exposure in question were estimated via Cox s regression models. RESULTS: During
      the SBP follow-up, the steepest SBP gradient was found for physical workload only
      and physical workload combined with noise; shift work alone or combined with
      noise primarily entailed a lower mean SBP level than no such exposure. However,
      the shift workers had a relative risk of 1.71 [95% confidence interval (95% CI)
      1.01-2.87] even without an increase in SBP, but, with a baseline SBP of > or =
      140 mmHg and an additional increase, their relative risk rose to 4.62 (95% CI
      2.31-9.24) when they were compared with day workers with an SBP of <140 mmHg and
      no increase. CONCLUSIONS: In general, shift workers do not develop higher SBP
      levels than day workers, but, if they do, it entails high CHD risk. Noise shows a
      similar pattern. In contrast, physical workload entails a significant increase in
      SBP, and SBP is a key pathway to CHD risk.

PMID- 18327511
TI  - Ischemic stroke and shift work.
AB  - OBJECTIVES: This study analyzed the potential association between shift work and
      ischemic stroke. METHODS: The analysis was carried out using a nested case
      control study consisting of 138 shift workers and 469 day workers from the
      register of the Northern Sweden Monitoring of Trends and Determinants in
      Cardiovascular Diseases (MONICA) study and the Vasterbotten Intervention
      Programme. Logistic regression analysis was used to analyze the risk estimate for
      day workers in a comparison with shift workers and the risk of ischemic stroke.
      RESULTS: The crude odds ratio for shift workers' risk of experiencing an ischemic
      stroke was 1.0 (95% confidence interval 0.6-1.8) for both the men and the women.
      The risk estimates were consistent despite the introduction of several recognized
      risk factors for ischemic stroke in the logistic regression models. CONCLUSIONS:
      In the present study, none of the findings indicated a higher risk of shift
      workers undergoing an ischemic stroke than day workers.

PMID- 18327512
TI  - Generalizability of a prediction rule for sick leave due to shoulder pain.
AB  - OBJECTIVES: Recently, a rule was developed to predict sick leave related to
      shoulder pain during a period of 6 months after patients have consulted a general
      practitioner for a new episode of shoulder pain. The objective was to evaluate
      the generalizability of this prediction rule by testing it in two other
      populations of workers who had gone for a consultation in primary care for a new
      episode of shoulder pain. METHODS: The prediction rule was derived in a
      prognostic cohort study (N=350). The outcome was sick leave related to shoulder
      pain during 6 months following the first consultation. The rule was tested on
      merged control groups from three trials on shoulder pain (N=128). In addition to
      this population, a recently conducted study on musculoskeletal disorders (N=224)
      was used to validate the prediction rule. The generalizability of the prediction
      rule was tested by studying calibration and discrimination in the validation
      cohorts. RESULTS: The prediction rule showed reasonable calibration in both
      validation cohorts. The discriminative ability, with an area under the receiver
      operating characteristic (ROC) curve (AUC) of 0.70 in the derivation cohort was
      stable in the cohort of the musculoskeletal disorder study (AUC 0.71). In the
      control groups of the three randomized controlled trials of a Dutch shoulder
      study, the discriminative ability decreased to an AUC of 0.66. CONCLUSIONS: The
      prediction rule for sick leave related to shoulder pain in a 6-month period
      following the first consultation in primary care showed adequate generalizability
      to another population of workers with shoulder pain participating in an
      observational cohort study. In the control groups of the three randomized
      controlled trials the prediction rule performed less well.

PMID- 18327513
TI  - Neuropsychological and positron emission tomography correlates in idiopathic
      environmental intolerances.
AB  - OBJECTIVES: It has been hypothesized that people with subjective hypersensitivity
      to chemicals may indeed suffer from neuronal damage due to widely distributed
      environmental toxins and that such deficits of diagnostic importance can be
      demonstrated with the help of functional neuroimaging even in single cases. In
      this study, a small group of well-characterized patients with idiopathic
      environmental intolerance were examined in order to identify such changes.
      METHODS: Twelve patients with idiopathic environmental intolerance were
      investigated neuropsychologically and underwent cerebral F-18 fluorodeoxyglucose
      (F-18 FDG) positron emission tomography (PET). The imaging results were compared
      with findings from 17 healthy controls. RESULTS: Six patients showed deficits in
      verbal learning and memory, three of them also had a reduced information
      processing speed. In the individual analyses, 11 patients showed normal cerebral
      glucose metabolism. In the group analysis of the patients, no areas with
      significantly reduced glucose metabolism could be found. CONCLUSIONS: No
      consistent pathological cognitive performance and functional imaging pattern was
      found. It appears premature to claim specific neuropsychological or neuroimaging
      findings characteristic of idiopathic environmental intolerance. Therefore
      cerebral F-18 FDG PET should not be used to corroborate or rule out suspected
      idiopathic environmental intolerance, a syndrome whose potential biological
      underpinnings still need to be clarified.

PMID- 18327514
TI  - Male bladder cancer risk and occupational exposure according to a job-exposure
      matrix-a case-control study in British Columbia, Canada.
AB  - OBJECTIVES: The authors investigated the risk of bladder cancer in association
      with exposure to over 12 000 occupational chemical agents, complex mixtures, and
      other substances (hereafter referred to as chemical agents). METHODS: Adult males
      diagnosed with cancer between 1983 and 1990 in British Columbia, Canada, were
      surveyed. Detailed occupational histories and confounding information was
      provided by a self-administered questionnaire. Cancer controls were matched to
      bladder cancer cases, resulting in 1062 cases and 8057 controls for the analysis.
      An extensive United-States-based job-exposure matrix was applied to estimate
      cumulative exposure to occupational chemical agents. Odds ratios for bladder
      cancer due to exposure to chemical agents were estimated via conditional logistic
      regression analyses, adjusted for important confounders. RESULTS: A significantly
      (P<0.05) increased risk was detected for ever exposure to 635 chemical agents,
      and 341 chemical agents exhibited a significantly increasing dose-response
      relationship. Adjustment for multiple comparisons resulted in a subset of 29
      chemical agents that continued to show significant results. A principal
      components analysis classified these 29 chemical agents into five independent
      groups, distinguished mainly by job. Exposures to these chemical agents were
      largely due to employment in the logging and construction industries and
      occupations involving motor vehicles. Consistent results were observed for
      bladder carcinogens reported in the literature. CONCLUSIONS: This study suggests
      that several specific chemical agents were significantly associated with the risk
      of bladder cancer. The chemical agents were mainly derivatives or combustion
      products of fossil fuels. The results corroborate important findings from the
      literature and document a risk for specific chemical agents not previously
      reported.

PMID- 18327515
TI  - Time trends in cancer risk and pesticide exposure, a long-term follow-up of
      Danish gardeners.
AB  - OBJECTIVES: Occupational exposure to petrochemical pesticides was high during the
      first 10-15 years after their introduction in the late 1940s, and, during these
      years, many cases of intoxication occurred. In the 1960s, the use and marketing
      of pesticides was regulated to reduce exposure to these substances, and, since
      1970, substantial exposure has been rare in Denmark. The present study aimed at
      investigating the extent to which these alterations have influenced the cancer
      risk of gardeners. METHODS: A historical cohort of 3156 male gardeners was
      followed from May 1975 until 2002 with regard to cancer incidence. RESULTS: The
      cancer incidence was significantly below the national average [standardized
      incidence ratio (SIR) 0.86, 95% confidence interval (95% CI) 0.79-0.94], but an
      analysis by birth cohort indicated marked differences with a downward tendency
      for younger birth cohorts. Among the gardeners born prior to 1915, significant
      increases were found for leukemia (12 cases, SIR 2.33, 95% CI 1.32-4.10) and soft
      tissue sarcoma (3 cases, SIR 5.87, 95% CI 1.89-18.20). CONCLUSIONS: Gardeners
      constitute a healthy worker group, but an increased risk of soft tissue sarcoma
      and leukemia is indicated for people born prior to 1915, a finding that may
      reflect substantial pesticide exposure during the late 1940s and the 1950s. Among
      the gardeners born in 1915 or later, no excess cancer risk was found. The latter
      finding suggests a cancer-preventive effect for safety recommendations and
      improved technical devices with respect to pesticide application, along with
      legislative control measures to reduce pesticide exposure.

PMID- 18327516
TI  - Cohort mortality study of Swedish pulp and paper mill workers-nonmalignant
      diseases.
AB  - OBJECTIVES: The aim of this study was to determine mortality among pulp and paper
      mill workers according to the main mill pulping process, department, and gender,
      particular reference being given to diseases of the circulatory and respiratory
      systems. METHODS: The cohort of 18 163 men and 2 291 women employed between 1939
      and 1999 and with >1 year of employment was followed for mortality from 1952 to
      2001 (acute myocardial infarction from 1969). Standardized mortality ratios (SMR)
      with 95% confidence intervals (95% CI) were estimated by comparing the observed
      number of deaths with the expected number for the entire Swedish population.
      Exposure was assessed from personnel files in the mills. Data from an exposure
      measurement database are also presented. RESULTS: There were 5898 deaths in the
      cohort. Total mortality had an SMR of 1.02 (95% CI 0.98-1.06) for the men in the
      sulfate mills and an SMR of 0.93 (95% CI 0.90-0.97) for the men in the sulfite
      mills. Mortality from acute myocardial infarction was increased among the men in
      both the sulfate and sulfite mills [SMR 1.22 (95% CI 1.12-1.32) and SMR 1.11 (95%
      CI 1.02-1.21), respectively] and by department in sulfate pulping (SMR 1.29, 95%
      CI 1.07-1.54), paper production (SMR 1.26, 95% CI 1.06-1.49), and maintenance
      (SMR 1.16, 95% CI 1.02-1.30). Mortality from cerebrovascular disease, diabetes
      mellitus, and nonmalignant respiratory diseases was not increased. CONCLUSIONS:
      Death from acute myocardial infarction, but not cerebrovascular diseases, was
      increased in this cohort and was probably related to a combination of different
      occupational exposures (eg, dust, sulfur compounds, shift work, and noise).

PMID- 18327517
TI  - [Hepatitis associated cryoglobulinemia].
AB  - Cryoglobulins are immunoglobulins that precipitate at temperatures below 37
      degrees C. Clinically cryoglobulinemia is manifested in a variety of symptoms on
      different organs. The most important clinical symptoms are fatigue, peripheral
      neuropathy and vasculitis associated skin lesions. Pathophysiologically
      cryoglobulinemia is based on a disturbed immunocascade with an elevated B-cell
      activity. Often a cryoglobulinemia progresses smoothly to a Non-Hodgkin-Lymphoma.
      The main activator of a cryoglobulinemia is a Hepatitis C virus infection. Other
      causes for developing a cryoglobulinemia are rheumatological and haematological
      diseases. In the past cryoglubulinemia has predominantly been treated with
      plasmapheresis and immunosuppression, nowadays antiviral strategies are becoming
      more important. Cases of rapid worsening under therapy with interferon alpha have
      also been reported. A promising new option is the use of rituximab.

PMID- 18327518
TI  - [The legal aspects of "off label use" -- or: Doubtful private prescription].

PMID- 18327522
TI  - Training, attitudes and practice of district health workers in Kenya.
AB  - BACKGROUND: The 1994 mental health policy in Kenya was rooted in the concepts of
      Primary Health Care articulated at Alma Ata, and required that mental health care
      be decentralized to all levels of the health care system, and delivered by all
      cadres of health staff rather than just mental health specialists. However,
      effective implementation of this policy was likely to be influenced by the degree
      to which the training, attitudes and practice of health staff was consistent with
      and supportive of the mental health policy. OBJECTIVE: This article therefore
      reports a study conducted in 1997, which examined the training, attitudes and
      practice of district level health staff in relation to mental health care and
      compared them with the national mental health policy of 1994. METHOD: A semi
      structured questionnaire was sent to the medical superintendents of all district
      hospitals in Kenya, for distribution to respondents from each cadre of health
      staff. A total of 148 health workers from 28 districts out of 44 eligible
      districts (63%) responded. RESULTS: District health workers did not think general
      health workers ought to manage most psychiatric patients, even if they were
      capable of doing so, preferring a system where these patients were managed by
      specialists and were not admitted into general wards. They also tended to equate
      mental illness with psychosis. CONCLUSION: Despite their training in mental
      health care and their theoretical knowledge of the principles of Primary Health
      Care, the attitude and mental health care practice of most health workers were in
      keeping with a more medical model of health care, emphasising pharmacological
      treatment and expecting psychiatric patients to conform to the standard Sick
      Role. This orientation, being at variance with the orientation of the 1994 mental
      health policy, may have contributed to difficulties in implementation of the
      policy.

PMID- 18327523
TI  - Mortality associated with depression: a forty-year perspective from the Stirling
      County Study.
AB  - BACKGROUND: This report concerns long-term mortality risks associated with
      depression, and the potentially confounding factors of alcoholism and cigarette
      smoking, as experienced by a general population assessed at a baseline in 1952,
      followed for re-assessment of survivors in 1968, and for death by 1992. METHODS:
      Self-report and physician-report information was gathered in 1952 and again in
      1968 about a sample of 1,079 adults. At the end of follow-up in 1992, the vital
      status of all subjects was known. Comorbidity among depression, alcoholism, and
      smoking was investigated. Cox regression models were employed to estimate hazard
      ratios (HRs) as indicators of mortality risk. Models including age, gender, and
      depression were fit for the complete sample at baseline as well as for re
      assessed survivors. Models simultaneously controlling for the mortality risks
      associated with depression, alcoholism, and heavy smoking were fit for men.
      RESULTS: At the baseline in 1952, depression was somewhat more common among women
      than men (4% compared to 6%) but was found to carry a significant mortality risk
      only among men (HR 2.7, 95% CI 1.6-4.7). Based on re-assessments made in 1968,
      depression was associated with mortality risk among both men (HR 2.2, 95% CI 1.0
      4.5) and women (HR 2.1, 95% CI 1.2-3.8). In 1952, more than 20% of men smoked
      cigarettes excessively and 8% abused alcohol, but very few of these groups of men
      were also depressed. In the original sample and also among the survivors,
      depression, alcoholism, and heavy smoking were separately associated with
      mortality among men. Depression and alcoholism carried a more immediate mortality
      risk while heavy smoking a more delayed one. CONCLUSIONS: At the baseline of the
      Stirling County Study, the mortality risk associated with depression among men
      was not enhanced or explained by abuse of alcohol or nicotine, mainly because
      comorbidity was rare at that time. The longitudinal research of the study has
      pointed to a number of psychiatrically-relevant time-trends such as the fact that
      an association between depression and cigarette smoking did not appear until the
      1990s. It is hypothesized that a similar trend may emerge over time regarding the
      comorbidity of depression and alcoholism. A trend reported here was that, while
      depressed women in the original sample did not carry a significant mortality
      risk, the surviving women who were depressed at the time of re-assessment
      exhibited a mortality risk that was as significant as that for men. Such
      information may provide a useful back-drop for future investigations.

PMID- 18327524
TI  - What is a surgical complication?

PMID- 18327525
TI  - What is the evidence for endoscopic thyroidectomy in the management of benign
      thyroid disease?
AB  - BACKGROUND: Endoscopic thyroidectomy (ET) is a demanding surgical technique in
      which dissection of the gland is entirely performed with an endoscope, in a
      closed area maintained by insufflation or mechanical retraction. ET by direct
      cervical approach (anterior or lateral) is minimally invasive, but ET using an
      extracervical access (chest wall, breast, or axillary) is not. No technique seems
      to be universally accepted yet. This review was designed to clarify the existing
      evidence for performing endoscopic thyroid resections in the management of benign
      thyroid nodules. METHODS: A database search was conducted in PubMed and Embase
      from which summaries and abstracts were screened for relevant data, matching our
      definition. Publications were further assessed and assigned their respective
      levels of evidence. Additional data derived from our own unit's experience with
      endoscopic thyroidectomy were included. RESULTS: Thirty mainly retrospective
      cohort studies have been published in which morbidity, such as unilateral vocal
      cord palsy, is poorly evaluated. ET takes from 90 to 280 minutes for lobectomy by
      cervical access and total thyroidectomy by chest wall approach, respectively.
      Cosmetic outcome in extracervical approach is less troubled by size of the
      resected specimen compared with direct cervical approach. Extracervical approach
      avoids a neck scar but implies invasiveness in terms of dissection and
      postoperative discomfort. Long-term cosmetic outcome comparisons with
      conventional thyroidectomy have not been published. CONCLUSIONS: Currently it is
      not possible to recommend the application of ET based on evidence. Reported
      complications stress the importance of advanced endoscopic skills. ET should only
      be offered to carefully selected patients and, therefore, a high volume of
      patients requiring thyroid surgery is needed. Superiority of endoscopic to
      conventional thyroidectomy has yet to be demonstrated. Possible advantages of
      endoscopic thyroid techniques and our patient's desire for the highest cosmetic
      outcome possible justify further development of ET in expert hands of endocrine
      surgeons.

PMID- 18327526
TI  - Surgical treatment of Graves' disease: evidence-based approach.
AB  - BACKGROUND: The optimal treatment of Graves disease (GD) is still controversial.
      Surgery is one treatment option along with radioactive iodine (RAI) and
      antithyroid medication. In this evidence-based review, we examine four issues:
      (1) Is surgery better than RAI or long-term antithyroid medication? (2) What is
      the recommended surgical approach? (3) How does the presence of Graves'
      ophthalmopathy (GO) influence the role of surgery? (4) What is the role of
      surgery in children with GD? METHODS: We conducted a systematic review of the
      literature using evidence-based criteria regarding these four issues. RESULTS:
      (1) There are no recommendations reaching any grade of evidence for which
      treatment to choose for adults with GD. (2) Total thyroidectomy has complication
      rates equal to those seen with lesser resections but it has higher cure rates and
      negligible recurrence rates (Level I-IV data leading to a grade A
      recommendation). (3) Data support surgery when severe GO is present, but RAI
      combined with glucocorticoids may be equally safe (Level II-IV data, grade B
      recommendation). The extent of thyroid resection does not influence the outcome
      of GO (Level II data, grade B recommendation). (4) Based on the available data,
      definitive treatment can be advocated for children (Level IV data, grade C
      recommendation) using either RAI or surgery. No recommendation can be given as to
      whether RAI or surgery is preferred owing to the lack of studies addressing this
      issue. Increased cancer risk with RAI in children below the age of 5 years
      supports surgery in this setting (Level I data, grade A recommendation).
      CONCLUSION: If surgery is considered for definitive management, evidence-based
      criteria support total thyroidectomy as the surgical technique of choice for GD.
      Available evidence also supports surgery in the presence of severe endocrine GO.
      Children with GD should be treated with an ablative strategy. Whether this is
      achieved by total thyroidectomy or RAI may still be debatable. Data on long-term
      cancer risk are missing or conflicting; and until RAI has proven harmless in
      children, we continue to recommend surgery in this group.

PMID- 18327528
TI  - Do benign thyroid nodules have malignant potential? An evidence-based review.
AB  - BACKGROUND: Benign thyroid tumors account for most nodular thyroid disease.
      Determination of whether a thyroid nodule is benign or malignant is a major
      clinical dilemma and underlies the decision to proceed to surgery in many
      patients. Although the accuracy of thyroid nodule fine-needle aspiration (FNA)
      has reduced the need for surgery over the years, questions regarding how to
      follow FNA-designated benign nodules remain unresolved. This is true at least in
      part because of uncertainty over whether some benign nodules harbor malignant
      potential. METHODS: An evidence-based review of recent clinical, pathologic, and
      molecular data is presented. A summary of data and observations from our own
      experience is also provided. RESULTS: Review of our recent 10-year experience
      indicates that 2% of thyroid malignancies arise within a preexisting benign
      thyroid nodule. In addition, both cytologic and molecular tumor markers,
      including Gal-3, CITED1, HBME-1, Ras, RET/PTC, and PAX8/PPAR gamma, have been
      identified in some histopathologically classified benign nodules. Gene expression
      profiling suggests that follicular adenomas and Hurthle cell adenomas have
      similarities to both benign and malignant tumors, suggesting that some of these
      tumors are premalignant. In addition, 10% of surgically excised follicular tumors
      are encapsulated follicular lesions with nuclear atypia, which have been termed
      "well-differentiated tumors of uncertain malignant potential." The data available
      suggest that these tumors could be precursors to carcinoma. CONCLUSION: Some
      benign thyroid nodules have malignant potential. Further molecular testing of
      these tumors can shed light on the pathogenesis of early malignant
      transformation.

PMID- 18327529
TI  - A place for radiofrequency ablation in the treatment of resectable colorectal
      liver metastases?

PMID- 18327530
TI  - Lymph node ratio: role in the staging of node-positive colon cancer.
AB  - BACKGROUND: Recent literature has shown that lymph node ratio (LNR) is superior
      to the number of positive lymph nodes (pLNs) in predicting the prognosis in
      several malignances other than colon cancer. We hypothesize that LNR may play a
      similar role in stage III colon cancer. METHODS: We included 24,477 stage III
      colon cancer cases from the Surveillance, Epidemiology, and End Results cancer
      registry. Patients were categorized into four groups, LNR1 to 4, according to
      cutoff points 1/14, 0.25, and 0.50. Kaplan-Meier and Cox proportional hazard
      model were used to evaluate the prognostic effect and estimate the relative risk
      (RR) and 95% confidence interval (CI) of LNR. RESULTS: The 5-year survival for
      patients with stage IIIA, IIIB, and IIIC was 71.3%, 51.7%, and 34.0%,
      respectively (P < .0001). There was no survival difference among LNR1 to LNR4 for
      stage IIIA patients. In stage IIIB patients, the 5-year survival for those with
      LNR1 to LNR4 was 63.5%, 54.7%, 44.4%, and 34.2%, respectively (P < .0001). In
      stage IIIC patients, the 5-year survival for those with LNR2 to LNR4 was 49.6%,
      41.7%, and 25.2%, respectively (P < .0001). LNR is an independent predictor of
      survival after adjusting patient's age, tumor size, tumor grade, race, number of
      pLNs, and total number of LNs harvested. (RR 2.30, 95% CI 2.08-2.55). CONCLUSION:
      Patients with stage IIIB and IIIC colon cancer represent a heterogeneous group of
      patients with the majority either overstaged or understaged. LNR is a more
      accurate prognostic method for stage III colon cancer patients. We propose an
      algorithm to incorporate LNR into current AJCC staging system.

PMID- 18327531
TI  - Exploring leadership competencies in established and aspiring physician leaders:
      an interview-based study.
AB  - BACKGROUND AND OBJECTIVES: Academic health care institutions have become
      interested in understanding and supporting current leaders and preparing leaders
      for the future. We designed this exploratory study to better understand specific
      perceived leadership needs of physicians from the perspective of "aspiring" and
      "established" leaders within our institution. DESIGN: A qualitative, inductive,
      structured interview-based design was used to examine the study questions.
      PARTICIPANTS: A purposeful sample of current and aspiring leaders was obtained,
      sampling across specialties and levels of leadership. INTERVENTIONS: All
      participants were interviewed by the same investigator (CT). Five open-ended
      questions were developed as prompts. Two of the investigators independently
      analyzed the transcripts, using an open coding method to identify themes within
      the narratives. Inter-observer comparisons were made and discrepancies were
      resolved through discussion. RESULTS: Four themes emerged from analyzing the
      responses to our questions. Aspiring and established leaders agreed that
      "knowledge", "people skills" or emotional intelligence, and "vision" were all
      characteristics of effective leaders and critical to the success of aspiring
      leaders. Established leaders in our sample added a characteristic of
      "organizational orientation" that extended the description of "leaders" to
      include an understanding of the institution as well as dedication to its success
      (a trait we have called "organizational altruism"). CONCLUSIONS: Our findings
      validate others' regarding leadership competencies while extending these findings
      to the specific context of health care and physicians. Important implications for
      curricular design include: inclusion of emotional intelligence competencies and
      reducing formal didactics in favor of programs that are both interactive and
      problem-based.

PMID- 18327533
TI  - Effects of cocaine in 5-lipoxygenase-deficient mice.
AB  - 5-Lipoxygenase (5-LOX), along with 12-lipoxygenase and cyclooxygenases,
      metabolizes arachidonic acid into eicosanoids. In rodents, 12-lipoxygenase
      deficiency alters behavioral responses to cocaine. We used 5-LOX-deficient mice
      and their controls to investigate cocaine's actions. After repeated cocaine
      injections, the increase in locomotor activity was greater in 5-LOX-deficient
      mice. Since the 5-LOX pathway may regulate the levels/metabolism of
      arachidonoylethanolamide (AEA) we assayed the AEA levels in the striatum, the
      binding of the endogenous AEA to the cannabinoid receptor CB1R, and anandamide
      hydrolase (FAAH) activity in the striatum, hippocampus, and cortex. Striatal AEA
      levels decreased after repeated cocaine injections. Cocaine also decreased CB1R
      binding in all brain regions studied and the only significant differences between
      5-LOX-deficient and control mice was the greater hippocampal FAAH activity in 5
      LOX-deficient mice. Our results demonstrated that a 5-LOX deficiency alters
      sensitivity to repeated cocaine. It should be investigated whether a human 5-LOX
      gene polymorphism affects cocaine's actions.

PMID- 18327532
TI  - Bladder and bowel dysfunction in Parkinson's disease.
AB  - Bladder dysfunction (urinary urgency/frequency) and bowel dysfunction
      (constipation) are common non-motor disorders in Parkinson's disease (PD). In
      contrast to motor disorder, the pelvic autonomic dysfunction is often non
      responsive to levodopa treatment. Brain pathology mostly accounts for the bladder
      dysfunction (appearance of overactivity) via altered dopamine-basal ganglia
      circuit, which normally suppresses the micturition reflex. In contrast,
      peripheral enteric pathology mostly accounts for the bowel dysfunction (slow
      transit and decreased phasic contraction) via altered dopamine-enteric nervous
      system circuit, which normally promotes the peristaltic reflex. In addition, weak
      strain and paradoxical anal contraction might be the results of brain pathology.
      Pathophysiology of the pelvic organ dysfunction in PD differs from that in
      multiple system atrophy; therefore it might aid the differential diagnosis. Drugs
      to treat bladder dysfunction in PD include anticholinergic agents. Drugs to treat
      bowel dysfunction in PD include dietary fibers, peripheral dopaminergic
      antagonists, and selective serotonergic agonists. These treatments might be
      beneficial not only in maximizing patients' quality of life, but also in
      promoting intestinal absorption of levodopa and avoiding gastrointestinal
      emergency.

PMID- 18327534
TI  - Phase behavior of flowerlike micelles in a SCF cell model.
AB  - We study the interactions between flowerlike micelles, self-assembled from
      telechelic associative polymers, using a molecular self-consistent field (SCF)
      theory and discuss the corresponding phase behavior. In these calculations we do
      not impose properties such as aggregation number, micellar structure and number
      of bridging chains. Adopting a SCF cell model, we calculate the free energy of
      interaction between a central micelle surrounded by others. Based on these
      results, we predict the binodal for coexistence of dilute and dense liquid
      phases, as a function of the length of the hydrophobic and hydrophilic blocks. In
      the same cell model we compute the number of bridges between micelles, allowing
      us to predict the network transition. Several quantitative trends obtained from
      the numerical results can be rationalized in terms of transparent scaling
      arguments.

PMID- 18327536
TI  - A descriptive evaluation of unfractionated heparin use during pregnancy.
AB  - BACKGROUND: The mainstay of oral anticoagulant therapy, warfarin sodium, crosses
      the placenta during pregnancy and may cause fetal complications. Unfractionated
      heparin (UFH) and low-molecular-weight heparin (LMWH) do not cross the placenta
      and have demonstrated utility in the prevention and treatment of thrombosis
      during pregnancy. OBJECTIVES: The purpose of this study was to review treatment
      strategy, indication, and maternal and fetal outcomes in anticoagulated
      pregnancies at Kaiser Permanente Colorado. PATIENTS/METHODS: We identified 103
      pregnancies in 93 mothers prescribed an anticoagulant during a pregnancy
      occurring between January 1, 1998 and March 31, 2005. RESULTS: The majority of
      patients were treated with UFH (89.3%). Indications for anticoagulation included
      venous thromboembolism (VTE) prophylaxis (53.4%), history of pregnancy loss
      (29.1%), acute VTE (16.5%), and history of cerebral vascular accident (CVA)
      (1.0%). There were no maternal deaths. Fetal demise occurred in 8 pregnancies
      (7.8%) at a median 14 weeks gestation (range 7-22 weeks). No fetal demise
      occurred in pregnancies treated for acute VTE or history of CVA. There were two
      occurrences of pulmonary embolism (1.9%) and two hemorrhagic events requiring
      transfusion (1.9%). CONCLUSIONS: Maternal and fetal adverse events were
      infrequent in our population of anticoagulated pregnancies. UFH remains a viable
      option among more expensive LMWH products.

PMID- 18327537
TI  - Importance of temperature and anodic medium composition on microbial fuel cell
      (MFC) performance.
AB  - The performance of a microbial fuel cell (MFC) was investigated at different
      temperatures and anodic media. A lag phase of 30 h occurred at 30 degrees C which
      was half that at room temperature (22 degrees C). The maximum power density at 30
      degrees C was 70 mW/m(2) and at 22 degrees C was 43 mW/m(2). At 15 degrees C, no
      successful operation was observed even after several loadings for a long period
      of operation. Maximum power density of 320 mW/m(2) was obtained with wastewater
      medium containing phosphate buffer (conductivity: 11.8 mS/cm), which was approx.
      4 times higher than the value without phosphate additions (2.89 mS/cm).

PMID- 18327538
TI  - Inhibitory effects of substrate and product on the carvone biotransformation
      activity of Rhodococcus erythropolis.
AB  - The aqueous substrate and product toxicity thresholds in the microbial
      biotransformation of (-)-trans-carveol to the fragrance/flavor compound (R)-(-)
      carvone by Rhodococcus erythropolis were determined. Above aqueous phase
      concentrations of approx. 500 mg carveol/l and 200-600 mg carvone/l, the
      biotransformation activity of the biocatalyst was inhibited. This
      biotransformation was undertaken in a single aqueous phase 3 l [corrected]
      reactor in which a total of 5 ml carveol (mixture of isomers) was added before
      the biotransformation rate decreased significantly. The carvone volumetric
      productivity was 31 mg/lh. Although the growth of the organism post-exposure was
      not affected, dramatic morphological changes in response to the accumulation of
      the inhibitory substrate and product were observed.

PMID- 18327539
TI  - Antimicrobial peptide P18 inhibits inflammatory responses by LPS- but not by IFN
      gamma-stimulated macrophages.
AB  - Antimicrobial peptide P18 markedly inhibited the expression of inducible nitric
      oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1
      beta (IL-1beta) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells,
      whereas magainin 2 did not inhibit these activities. P18 dose-dependently reduced
      nitric oxide (NO) production by LPS-stimulated RAW 264.7 macrophage cells, with
      complete inhibition at 20 microg P18 ml(-1). In contrast, P18 had no effect on NO
      production and the expression of iNOS mRNA and iNOS protein by interferon-gamma
      (IFN-gamma)-stimulated RAW264.7 cells, suggesting P18 selectively inhibits LPS
      stimulated inflammatory responses in macrophages. An LAL assay showed that P18
      has strong LPS-neutralizing activity, indicating that P18 inhibits the
      inflammatory responses in LPS-stimulated macrophages by direct binding to LPS.
      Collectively, our results indicate that P18 has promising therapeutic potential
      as a novel anti-inflammatory as well as antimicrobial agent.

PMID- 18327540
TI  - Biotechnological implications of filamentation in Saccharomyces cerevisiae.
AB  - The genetics governing the morphological switch from round or ovoid cells to
      filamentous growth in Saccharomyces cerevisiae has received significant interest
      in relation to sensing and signaling pathways as well as the control of cell
      processes including budding, elongation and adhesion. Little is known about the
      environmental signals which trigger these morphological changes from a
      biotechnological point of view. This review aims to highlight the main causes of
      filamentous growth in S. cerevisiae in its industrial setting with the purpose of
      stimulating additional studies within this field.

PMID- 18327541
TI  - Pretreatment characteristics of waste oak wood by ammonia percolation.
AB  - A log of waste oak wood collected from a Korean mushroom farm has been tested for
      ammonia percolation pretreatment. The waste log has different physical
      characteristics from that of virgin oak wood. The density of the waste wood was
      30% lower than that of virgin oak wood. However, there is little difference in
      the chemical compositions between the woods. Due to the difference in physical
      characteristics, the optimal pretreatment conditions were also quite different.
      While for waste oak the optimum temperature was determined to be 130 degrees C,
      for virgin oak wood the optimum pretreatment was only achieved at 170 degrees C.
      Presoaking for 12 h with ammonia solution before pretreatment was helpful to
      increase the delignification efficiency.

PMID- 18327542
TI  - Sugarcane bagasse mild alkaline/oxidative pretreatment for ethanol production by
      alkaline recycle process.
AB  - In order to decrease the alkali and water consumptions in the sugarcane bagasse
      alkaline/oxidative pretreatment for ethanol production, an alkaline recycle
      process was carried out. Two recycles of NaOH/H2O2 pretreatment did not decrease
      the pretreatment and enzymatic hydrolysis efficiencies and the consumptions of
      NaOH and water would be saved by 26% and 40%, respectively. A simultaneous
      saccharification and fermentation (SSF) culture with pretreated bagasse as
      substrate was developed giving 25 g ethanol l(-1) with a yield of 0.2 g g(-1)
      bagasse and productivity of 0.52 g l(-1) h(-1).

PMID- 18327543
TI  - Biotreatment of high strength nitrate waste using immobilized preadapted sludge.
AB  - One of the major wastes generated by fertilizer, explosive, and nuclear
      industries are nitrate (as high as 1,000 ppm NO(3)N) whose removal before
      disposal has become a growing concern. In this study, an active denitrifying
      sludge was immobilized onto support materials like cloth and polyurethane foam
      and their denitrification efficiency on high nitrate wastes [1,000 ppm NO(3) (225
      ppm NO(3)N), 5,000 ppm NO(3) (1,129 ppm NO(3)N), 7,500 ppm NO(3) (1,693 ppm NO(3)
      N)] was studied. Results showed complete degradation of the nitrate wastes (225
      ppm NO(3)N, 1,129 ppm NO(3)N, and 1,693 ppm NO(3)N) without any accumulation of
      nitrite in a period of only 1, 4, and 10 h, respectively. Based on adhering and
      entrapment principle, an immobilization unit was developed using a combination of
      cloth and foam as well as both individually. This system used for treating such
      high nitrate wastes was found to be quite effective in waste water treatment,
      particularly in problems associated with solid-liquid separation. The batch
      column reactor was run in about 45 batches without any loss in activity or
      reactor stability.

PMID- 18327544
TI  - Evaluation of lignocellulosic wastes for production of edible mushrooms.
AB  - The degradation of lignocellulosic wastes such as paddy straw, sorghum stalk, and
      banana pseudostem was investigated during solid-state fermentation by edible
      mushrooms Pleurotus eous and Lentinus connotus. Biological efficiency of 55-65%
      was observed in paddy straw followed by sorghum stalk (45%) and banana pseudostem
      (33%) for both fungal species. The activity of extracellular enzymes, namely
      cellulase, polyphenol oxidase, and laccase, together with the content of
      cellulose, lignin, and phenols, was studied in spent substrates on seventh, 17th,
      and 27th days of spawning, and these values were used as indicators of the extent
      of lignocellulosic degradation by mushroom. Both the mushroom species proved to
      be efficient degraders of lignocellulosic biomass of paddy straw and sorghum
      stalk, and the extent of cellulose degradation was 63-72% of dry weight (d.w.),
      and lignin degradation was 23-30% of the d.w. In banana pseudostem, the extent of
      the degradation was observed to be only 15-22% of the d.w. for both lignin and
      cellulose. Preferential removal of cellulose during initial growth period and
      delayed degradation of lignin were observed in all three substrates. This is
      associated with decrease in activity of cellulase and polyphenol oxidase and
      increase in laccase activity with spawn aging in spent substrates. Thus,
      bioconversion of lignocellulosic biomass by P. eous and L. connotus offers a
      promising way to convert low-quality biomass into an improved human food.

PMID- 18327545
TI  - Practical aspects of hydrophobic polycationic bactericidal "paints".
AB  - We previously discovered that coating solid surfaces with long-chained linear N
      dodecyl,N-methyl-polyethylenimine makes them bactericidal and virucidal. In the
      present study, focusing on the use of this microbicidal paint to kill airborne
      Escherichia coli and Staphylococcus aureus, we have systematically investigated
      the dependence of this effect on the concentration and mode of application of the
      hydrophobic polycation, the number of coats, the nature of the solvent, and the
      presence of a dye in such paint. In addition, the latter's ability to be
      regenerated after use, stability upon repeated washings, and mammalian toxicity
      has been evaluated.

PMID- 18327546
TI  - Comparison of Yarrowia lipolytica lipase immobilization yield of entrapment,
      adsorption, and covalent bond techniques.
AB  - The purpose of this study was to immobilize lipase from Yarrowia lipolytica using
      three methods including inclusion, adsorption, and covalent bond to study enzyme
      leaching, storage, and catalytic properties. Sodium alginate and chitosan were
      the polymers selected to immobilize lipase by inclusion. The beads of each
      polymer were dried by freeze drying and fluidization. The results show that
      chitosan was more adapted to the inclusion of lipase. Even though freeze dried,
      bead activity was low compared to that of fluidized beads. The freeze-drying
      process seems to produce suitable beads for storage at 4 and 20 degrees C. The
      immobilization by adsorption was carried out on both celite and silica gel.
      Maximum immobilization yield of 76% was obtained with celite followed by 43% in
      silica gel. The enzyme adsorbed on the two supports exhibited greater stability
      at a certain temperature (50 degrees C) and in no polar solvents (Isooctane, n
      heptane, and n-hexane). In addition, the lipase immobilized by covalent bond
      retained residual activity equitable to 70%. It was demonstrated that the enzyme
      immobilized by covalent bond showed greater activity (80%) after 5 months of
      storage.

PMID- 18327547
TI  - Morganella morganii-associated arthritis in a diabetic patient.
AB  - This case report involves a 60-year-old diabetic man who developed septic
      arthritis as a result of the pathogen Morganella morganii. The patient had
      complaints of elevated body temperature, malaise, rigors and pain in the left
      knee, despite no history of trauma. On examination of the knee, erythema, warmth,
      tenderness and swelling was observed. Arthrocentesis performed on his left knee
      indicated the presence of straw-coloured, cloudy fluid without crystals.
      Bacterial identification based on biochemical and automated methods indicated the
      growth of M morganii. M morganii was also isolated sedimentafrom the exudate of a
      diabetic ulcer in the left foot, with antibiotic susceptibilities identical to
      those from the knee effusion. This case indicates that M morganii may be
      considered as a possible cause of septic arthritis in diabetic patients,
      especially those with diabetic foot infections.

PMID- 18327548
TI  - Plasma antioxidants and human aging: a study on healthy elderly Tunisian
      population.
AB  - The aging has been described by several theories. It was proposed that free
      radicals are the major factor involved in this process. This gave birth to the
      free radical theory of aging. This current theory provides the most popular
      explanation for how aging occurs at the biochemical/molecular level. Ever since
      1956, this theory has received widespread attention and a large body of evidence
      has been accumulated in support of its hypotheses which were subsequently
      refined. The free radical theory of aging postulates that age-associated
      reductions in physiological functions are caused by an irreversible accumulation
      of oxidative alterations to macromolecules. This accumulation increases with age
      and is associated with the life expectancy of organisms. Moreover, this theory
      suggests the existence of an imbalance between reactive oxygen species (ROS)
      producing pathways and (ROS)-scavenging pathways, which is responsible for the
      generation of oxidative stress syndrome. In this article, we evaluate the
      antioxidant status in a population of healthy elderly Tunisians in comparison
      with a group of healthy young Tunisian subjects. This study sets out to
      investigate the age-related changes in glutathione peroxidase (GPx), superoxide
      dismutase (SOD) activities, and in total antioxidant status (TAS) of human
      plasma. We have concluded that healthy aging is accompanied with a disturbed
      antioxidant status.

PMID- 18327549
TI  - Production of recombinant human factor VIII in different cell lines and the
      effect of human XBP1 co-expression.
AB  - Recombinant factor VIII is one of the most complex mammalian proteins and a
      biotechnology venture required for the treatment of hemophilia A. The complexity
      of the protein, post-translational modifications and limitations of expression
      elements make the production of active recombinant FVIII a challenge. Here we
      report the production of biologically active Factor VIII in two different cell
      lines, CHO and HepG2, by transient transfection. Two expression vectors based on
      the CMV promoter were used: one harboring CMV Intron A (InA) and the other
      without it. To bypass difficulties in secretion, we also studied the influence of
      co-expression of the human splice isoform of the XBP1 gene. We report the
      production of recombinant FVIII possessing bioengineered FVIII heavy and light
      chains, linked by a minimal B domain. In our study, HepG2, a human hepatocyte
      cell line, expressed Factor VIII ten-fold more than a CHO cell line, and in HepG2
      cells, the expression of XBP1 improved Factor VIII activity. For CHO cells,
      expression was improved by the presence of InA, but no further improvement was
      noted with XBP1 co-expression. These data suggest that the minimal B domain
      rFVIII preserves Factor VIII biological activity and that different expression
      elements can be used to improve its production.

PMID- 18327550
TI  - Expression, purification, and in vivo administration of a promising anti
      idiotypic HIV-1 vaccine.
AB  - To date only a few neutralizing antibodies against HIV-1 exist. Since these
      neutralizing antibodies are only rarely found in sera of HIV-1 infected
      individuals an active vaccine is required. We recently developed murine anti
      idiotypic antibody Ab2/3H6 against monoclonal antibody (mAb) 2F5, which is one of
      the most prominent neutralizing antibodies. Anti-idiotypic antibody Ab2/3H6 has
      been partially humanized and expressed as whole immunoglobulin G in Chinese
      hamster ovary cells in order to minimize the human anti-mouse antibody response.
      Here we describe the expression, purification, and immunohistochemical
      characterization of the chimeric Ab2/3H6 Fab fragment, which was finally used
      beside the whole IgG1 as an antigen for immunization of guinea pigs. The crude
      sera were screened for specific antibodies against the epitope of mAb 2F5 ELDKWA
      as well as for reactivity against HIV-1 gp41.

PMID- 18327551
TI  - NUCEL (Cell and Molecular Therapy Center): a multidisciplinary center for
      translational research in Brazil.
AB  - Social and economical development is closely associated with technological
      innovation and a well-developed biotechnological industry. In the last few years,
      Brazil's scientific production has been steadily increasing; however, the number
      of patents is lagging behind, with technological and translational research
      requiring governmental incentive and reinforcement. The Cell and Molecular
      Therapy Center (NUCEL) was created to develop activities in the translational
      research field, addressing concrete problems found in biomedical and veterinary
      areas and actively searching for solutions by employing a genetic engineering
      approach to generate cell lines over-expressing recombinant proteins to be
      transferred to local biotech companies, aiming at furthering the development of a
      national competence for local production of biopharmaceuticals of widespread use
      and of life-saving importance. To this end, mammalian cell engineering
      technologies were used to generate cell lines over-expressing several different
      recombinant proteins of biomedical and biotechnological interest, namely,
      recombinant human Amylin/IAPP for diabetes treatment, human FVIII and FIX
      clotting factors for hemophilia, human and bovine FSH for fertility and
      reproduction, and human bone repair proteins (BMPs). Expression of some of these
      proteins is also being sought with the baculovirus/insect cell system (BEVS)
      which, in many cases, is able to deliver high-yield production of recombinant
      proteins with biological activity comparable to that of mammalian systems, but in
      a much more cost-effective manner. Transfer of some of these recombinant products
      to local Biotech companies has been pursued by taking advantage of the Sao Paulo
      State Foundation (FAPESP) and Federal Government (FINEP, CNPq) incentives for
      joint Research Development and Innovation partnership projects.

PMID- 18327552
TI  - Transient transfection factors for high-level recombinant protein production in
      suspension cultured mammalian cells.
AB  - The efficient transfection of cloned genes into mammalian cells system plays a
      critical role in the production of large quantities of recombinant proteins (r
      proteins). In order to establish a simple and scaleable transient protein
      production system, we have used a cationic lipid-based transfection reagent
      FreeStyle MAX to study transient transfection in serum-free suspension human
      embryonic kidney (HEK) 293 and Chinese hamster ovary (CHO) cells. We used
      quantification of green fluorescent protein (GFP) to monitor transfection
      efficiency and expression of a cloned human IgG antibody to monitor r-protein
      production. Parameters including transfection reagent concentration, DNA
      concentration, the time of complex formation, and the cell density at the time of
      transfection were analyzed and optimized. About 70% GFP-positive cells and 50-80
      mg/l of secreted IgG antibody were obtained in both HEK-293 and CHO cells under
      optimal conditions. Scale-up of the transfection system to 1 l resulted in
      similar transfection efficiency and protein production. In addition, we evaluated
      production of therapeutic proteins such as human erythropoietin and human blood
      coagulation factor IX in both HEK-293 and CHO cells. Our results showed that the
      higher quantity of protein production was obtained by using optimal transient
      transfection conditions in serum-free adapted suspension mammalian cells.

PMID- 18327553
TI  - Development of a high-throughput cell-based assay for 11beta-hydroxysteroid
      dehydrogenase type 1 using BacMam technology.
AB  - Cortisol is an important glucocorticoid in humans that regulates many
      physiological processes. Human 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) converts cortisone to cortisol in vivo and has emerged as an appealing
      therapeutic target for treating metabolic diseases. Here, we report a sensitive
      and robust high-throughput (HT) cell-based assay for screening 11beta-HSD1
      inhibitors. This assay utilizes a HEK293 cell line transduced by a BacMam virus
      expressing human 11beta-HSD1. The enzyme activity in the cells was measured by
      quantifying cortisol levels released into the cell culture supernatant via a
      competitive homogenous time-resolved fluorescence (HTRF) method. We show that
      11beta-HSD1 activity in supernatant of BacMam-transduced HEK293 cells increases
      with 11beta-HSD1 BacMam virus load in a dose-dependent manner, and is comparable
      to the enzyme activity detected in differentiated mouse adipocytes. In addition,
      we show that co-expression of hexose-6-phosphate dehydrogenase (H6PDH) is not
      required for the enzyme to function effectively as an oxo-reductase. This assay
      has been developed in low-volume 384-well format and it is sensitive, robust, and
      amenable to HT screening.

PMID- 18327554
TI  - Post-translational modifications of recombinant proteins: significance for
      biopharmaceuticals.
AB  - The production of recombinant therapeutic proteins is one of the fastest growing
      sectors of the pharmaceutical industry, particularly monoclonal antibodies and Fc
      fusion proteins. Currently, mammalian cells are the dominant production system
      for these proteins because they can perform complex post-translational
      modifications that are often required for efficient secretion, drug efficacy, and
      stability. These protein modifications include misfolding and aggregation,
      oxidation of methionine, deamidation of asparagine and glutamine, variable
      glycosylation, and proteolysis. Such modifications not only pose challenges for
      accurate and consistent bioprocessing, but also may have consequences for the
      patient in that incorrect modifications and aggregation can lead to an immune
      response to the therapeutic protein. This mini-review describes examples
      analytical and preventative advances in the fields of protein oxidation,
      deamidation, misfolding and aggregation (glycosylation is covered in other
      articles in this issue). The feasibility of partially replacing traditional
      analytical methods such as peptide mapping with high-throughput screens and their
      use in clone and media selection are evaluated. This review also discusses how
      further technical advances could improve the manufacturability, potency, and
      safety of biotherapeutics.

PMID- 18327555
TI  - Cells by design: a mini-review of targeting cell engineering using DNA
      microarrays.
AB  - Recent studies have demonstrated the utility of DNA microarray technology in
      engineering cellular properties. For instance, cellular adhesion, the necessity
      of cells to attach to a surface in order to to proliferate, was examined by
      comparing two distinct HeLa cell lines. Two genes, one encoding a type II
      membrane glycosylating sialyltransferase (siat7e) and the other encoding a
      secreted glycoprotein (lama4), were found to influence adhesion. The expression
      of siat7e correlated with reduced adhesion, whereas expression of lama4
      correlated with increased adhesion, as shown by various assays. In a separate
      example, a gene encoding a mitochondrial assembly protein (cox15) and a gene
      encoding a kinase (cdkl3), were found to influence cellular growth. Enhanced
      expression of either gene resulted in slightly higher specific growth rates and
      higher maximum cell densities for HeLa, HEK-293, and CHO cell lines. Another
      investigated property was the adaptation of HEK-293 cells to serum-free media.
      The genes egr1 and gas6, both with anti-apoptotic properties, were identified as
      potentially improving adaptability by impacting viability at low serum levels. In
      trying to control apoptosis, researchers found that by altering the expression
      levels of four genes faim, fadd, alg-2, and requiem, apoptotic response could be
      altered. In the present work, these and related studies in microorganisms
      (prokaryote and eukaryote) are examined in greater detail focusing on the
      approach of using DNA microarrays to direct cellular behavior by targeting select
      genes.

PMID- 18327556
TI  - Influence of a reduced CO2 environment on the secretion yield, potency and N
      glycan structures of recombinant thyrotropin from CHO cells.
AB  - A consistent increase of approximately 60% in the secretion yield of CHO-derived
      hTSH was observed by changing cell culture CO2 conditions from 5% CO2 to an air
      environment. The overall quality of the products obtained under both conditions
      was evaluated in comparison with a well-known biopharmaceutical (Thyrogen). The N
      glycans identified were of the complex type, presenting di-, tri- and tetra
      antennary structures, sometimes fucosylated, 86-88% of the identified structures
      being sialylated at variable levels. The three most abundant structures were
      monosialylated glycans, representing approximately 69% of all identified forms in
      the three preparations. The main difference was found in terms of antennarity,
      with 8-10% more di-antennary structures obtained in the absence of CO2 and 7-9%
      more tri-antennary structures in its presence. No remarkable difference in charge
      isomers was observed between the three preparations, the isoelectric focusing
      profiles showing six distinct bands in the 5.39-7.35 pI range. A considerably
      different distribution, with more forms in the acidic region, was observed,
      however, for two native pituitary preparations. All recombinant preparations
      showed a higher in vivo bioactivity when compared to native hTSH. Different
      production processes apparently do not greatly affect N-glycan structures, charge
      isomer distribution or bioactivity of CHO-derived hTSH.

PMID- 18327557
TI  - Rational vector design for efficient non-viral gene delivery: challenges facing
      the use of plasmid DNA.
AB  - Although non-viral gene delivery is a very straightforward technology, there are
      currently no FDA-approved gene medicinal products available. Therefore, improving
      potency, safety, and efficiency of current plasmid DNA vectors will be a major
      task for the near future. This article will provide an overview on factors
      influencing production yield and quality as well as safety issues that emerge
      from the vector design itself. Special focus will be on generating bacterial pDNA
      vectors by circumventing the use of antibiotic resistance genes, to generate
      safer gene medicinal products as well as smaller, more efficient DNA vectors.

PMID- 18327558
TI  - Pluronic enhances the robustness and reduces the cell attachment of mammalian
      cells.
AB  - The addition of the non-ionic surfactant, Pluronic F-68, to serum-free CHO
      cultures causes multi-functional effects that enhance cell yield in agitated
      cultures and reduce cell adhesion in stationary cultures. Three independent CHO
      cell lines were subjected to high liquid shear in assay systems that either
      included or excluded a liquid-gas interface. In the absence of Pluronic, there
      was a loss in cell viability in either assay system, although there was an
      intrinsic variability in sensitivity of the cell lines to shear damage.
      Supplementation with Pluronic prevented loss of cell viability, indicating
      protection in either a gas sparged or bubble-free environment. However, we found
      no evidence of long-term protection of cells once Pluronic was removed. Pluronic
      was capable of repairing trypsin-damaged cells as evidenced by enhanced growth,
      reduced membrane porosity, and improved robustness under liquid shear. The
      proportion of adherent cells was reduced to a minimal level by the presence of
      Pluronic although its effect was rapidly reversible with a high proportion (70%)
      of adherent cells observed within a few culture passages of its removal. The
      observed effects of Pluronic on these cultures are compatible with a mechanism in
      which the polymer forms a protective layer on the cell membrane, which has a
      significantly lower hydrophobicity.

PMID- 18327559
TI  - Identification of CHO endogenous promoter elements based on a genomic library
      approach.
AB  - Today the standard technology for the production of many biopharmaceutical
      products from mammalian cell systems is frequently based on expression vectors
      that utilize strong mammalian active viral promoters like CMV or SV40 for driving
      recombinant gene transcription. On one hand these promoters allow very high
      expression rates, but on the other hand, they can lead to constitutive over
      expression of the gene of interest resulting in a permanent stress on the cell.
      Another drawback is that they are cell cycle-dependent and can be subject to gene
      silencing which leads to a heterogeneity within the cell population. Here we aim
      to identify endogenous gene regulatory elements that are capable of controlling
      the transcription of the foreign gene. For this purpose, a genomic CHO library
      containing fragments of various lengths was constructed using a shotgun cloning
      strategy. After enzymatic fragmentation of genomic DNA, fragments encoding
      potential promoter regions were inserted into a promoterless vector upstream of
      the neomycin resistance gene. This random pool of library plasmids was
      transfected back into CHO cells and via cell sorting directly into 96-well plates
      and G418 (neomycin) selection, positive clones were isolated. A nested PCR of
      resistant CHO clones resulted in potential fragments which were sequenced.
      Putative promoter activity was predicted for these sequences by in silico methods
      and will be proved by re-transfection of reporter constructs into CHO cells.

PMID- 18327560
TI  - Lipofectamine RNAiMAX: an efficient siRNA transfection reagent in human embryonic
      stem cells.
AB  - RNA interference methodology suppresses specific gene expression, thus mimicking
      loss-of-function mutation and enabling in vitro and in vivo gene function
      analysis. Lipofectamine RNAiMAX, a new transfection reagent, has been confirmed
      high efficiency in delivering small interfering RNA (siRNA) into mesenchymal stem
      cells and neural stem cells. In this study, we used three transfection reagents
      (Lipofectamine RNAiMAX, Oligofectamine and Lipofectamine 2000) to deliver siRNA
      into human embryonic stem (hES) cells and compared the silencing efficiency of
      enhanced green fluorescent protein transgene and Oct4, a key regulator of
      pluripotency. As a result, siRNA can be delivered into hES cells more efficiently
      by Lipofectamine RNAiMAX compared with the other two transfection reagents and
      high efficient knockdown of target genes was obtained by Lipofectamine RNAiMAX
      even at a low concentration of siRNA. Quantitative real-time PCR showed
      approximately 90% knockdown of Oct4 transcript with cognate Oct4 siRNA
      transfection by Lipofectamine RNAiMAX compared to control siRNA. These results
      demonstrated that Lipofectamine RNAiMAX is an efficient and excellent
      transfection reagent for delivering siRNA into hES cells.

PMID- 18327561
TI  - [Bench reaches the bedside. Rethinking pathogen diagnostics].

PMID- 18327562
TI  - [Medical therapy of urinary tract infection].
AB  - Urinary tract infections (UTI) are the most common bacterial infectious diseases
      seen in the community, in most cases caused by E. coli. The treatment strategy
      differs depending on localization (lower vs. upper UT), acute uncomplicated vs.
      complicated infection, as well as for chronic disease and asymptomatic
      bacteriuria, the known or susceptible causative uropathogen with the (local)
      resistance pattern and the morbidity of the patient. There is a considerable
      worrying increase in the resistance rate of E. coli to TMP/SMX, quinolones and
      others. Most patients with uncomplicated, in the community acquired UTI are
      treated safely and effectively as out-patients. The available data support a
      short-course therapy with 3 days as the current standard therapy for lower UTI,
      but with a 7-14 days treatment for upper and complicated UTI. Recurrent UTI is
      best managed by low-dose antimicrobial prophylaxis for 3-6 (12 ore more) months.
      Besides that, new approaches to preventive strategies must prove their value in
      specific patient groups.

PMID- 18327563
TI  - ASK1 and MAP2K6 as modifiers of age at onset in Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominantly inherited neurodegenerative
      disease associated with abnormal expansions of a stretch of perfect CAG repeats
      in the HD gene. The number of repeat units is predictive for the age at onset
      (AO) of neurological symptoms. Part of the remaining variation in AO is
      attributed to modifier genes. In this study, genes involved in apoptosis were
      investigated as candidates for modulating AO in HD. A panel of 304 candidate
      genes was screened for allelic associations with motor AO via linked micro
      satellite markers by pooling the DNAs of HD individuals from opposite ends of the
      AO distribution. After genotyping promising markers from the pooling experiment
      individually, markers revealed consolidated evidence for association in a
      candidate region comprising the genes MAP3K5 (ASK1)/PEX7 at 6q23.3 and in the
      gene MAP2K6 at 17q24.3. Fine-mapping of these candidate regions in a cohort of
      250 Caucasian HD patients using single nucleotide polymorphism (SNP) markers
      delimitated the precise locations of association. Certain variations in an ASK1
      PEX7 haplotype block explain 2.6% of additional variance in AO in our HD cohort.
      In males, 4.9% additional variance could be attributed to MAP2K6 genotype
      variations. Altogether, ASK1-PEX7 haplotypes and MAP2K2 genotype variations
      explain 6.3% additional variance in AO for HD. We hypothesise that sequence
      variations of ASK1 and MAP2K6 lead to partially sex-specific changes in the
      levels and/or phosphorylation states of p38 and p38-regulated proteins that might
      contribute to the observed delaying effects in the AO of HD.

PMID- 18327564
TI  - [Treatment of intracapsular fractures of the femoral neck with a biaxial proximal
      femoral nail].
AB  - BACKGROUND: Intracapsular fractures of the femoral neck are mostly treated using
      individual cancellous screws or a dynamic hip screw in combination with anti
      rotational cancellous screws. The goal of this study was to evaluate the
      possibility of using proximal femoral nails for the surgical stabilisation of
      intracapsular fractures of the femoral neck. METHODS: A total of 58 patients (30
      male, 28 female) were evaluated in a retrospective study after a minimum
      postoperative follow-up of 24 months. The average length of time after surgery
      was 33.1 months. According to the AO classification, the following numbers of
      type 31B intracapsular fractures of the femoral neck were included in the study:
      by number, 20 cases of type 31B1, 12 cases of type 31B2 and 26 cases of 31B3. The
      biaxial proximal femoral nail (Targon PF, B. Braun, Aesculap(R), Germany) was the
      tested implant and was inserted using standard surgical techniques. RESULTS: No
      complications in healing were noted in 48 patients (82.8% of the study group) 2
      years following injury. The most frequent complication found was avascular
      necrosis of the head in seven patients (12.1%). Pseudoarthrosis formation was
      seen in two patients (3.4%), and other severe peroperative complications were
      observed in two other patients (3.4%). Reoperations were indicated in five
      patients, all of whom received a total hip endoprosthesis. We did not observe any
      refracture in the area of the implant. After 12 months 83% of the patients stated
      that they felt no or little pain. CONCLUSION: The results of our study have
      proven that the Targon PF biaxial proximal femoral nail may be used in treating
      intracapsular fractures of the femoral neck.

PMID- 18327565
TI  - Professor Rolf Luft, 1914--2007.

PMID- 18327567
TI  - Listeria monocytogenes internalins bind to the human intestinal mucin MUC2.
AB  - Listeria monocytogenes cross the intestinal barrier causing systemic infections
      with high mortality rates. Intestinal infection triggers release of intestinal
      mucus. We show that three L. monocytogenes internalins, InlB, InlC and InlJ all
      bound to MUC2 (the major component of intestinal mucus), but not to the cell
      surface mucin MUC1. Binding was strongest to InlB>InlC>InlJ (P < 0.001).
      Listerial internalins are characterized by their internalin domain, composed by
      leucine rich repeats (LRR) followed by an immunogloblin-like region. We report
      here that the internalin domain of the InlJ protein also bound MUC2, suggesting
      that an internalin domain is sufficient to bind to MUC2.

PMID- 18327566
TI  - Arthroscopic knee chondroplasty using a bipolar radiofrequency-based device
      compared to mechanical shaver: results of a prospective, randomized, controlled
      study.
AB  - Both mechanical shavers and radiofrequency-based devices are used to treat
      symptomatic partial thickness chondral lesions. Controversy exists as to which
      mode of treatment provides better outcomes. The purpose of this study was to
      compare clinical results after bipolar radiofrequency-based chondroplasty (RFC)
      to mechanical shaver debridement (MSD). Patients (n = 60) included in the study
      presented with knee pain associated with a medial meniscus tear and idiopathic
      ICRS grade III defect of the medial femoral condyle. Patients who had
      osteoarthritis, grade II or higher cartilage defects of the tibial joint surface,
      the lateral compartment, or the femoro-patellar joint, or had previously
      undergone surgery on the affected knee were excluded. Patients underwent partial
      meniscectomy; during the procedure, they were randomly assigned to receive
      bipolar RFC (Paragon, ArthroCare Corporation, Austin, TX) or MSD (Full radius
      resector LR 4.85 x 12.5 cm), Arthrex, Naples, FL). Postoperatively, the same
      physiotherapist provided instructions for a daily 2-h home training program
      consisting of isometric, isotonic, and leg lifting exercises; patients were
      provided the option of using crutches. Clinical outcomes were assessed using the
      Tegner score, visual analogue scale (VAS) score, and Knee and Osteoarthritis
      Outcome Score (KOOS) assessment, which consists of five principal domains
      including pain, symptoms, function in daily living (ADL), and knee related
      quality of life (QOL), where a score of 0 indicates extreme symptoms and 100
      represents no symptoms. Age and time from injury onset did not differ
      significantly between the RFC and MSD groups (43 +/- 10 vs. 44 +/- 9 years, P =
      0.732; 8 +/- 3 vs. 7 +/- 4 months, P = 0.279). No complications or adverse events
      were observed. Preoperatively, mean (+/-SD) scores for all KOOS principal domains
      were <20 and did not differ significantly (P > 0.05) between treatment groups.
      Postoperatively, the RFC patients returned to activity significantly earlier than
      MSD patients (17 +/- 7 vs. 22 +/- 6 days, P = 0.002). VAS pain scores at 6 h, 24
      h, 6 weeks, and 1 year were significantly (P < 0.001) lower for the RFC group
      than for the MSD group (4 +/- 2, 2 +/- 0.5, 2 +/- 1, 2 +/- 1 vs. 8 +/- 1, 4 +/-
      1, 4 +/- 1, 3 +/- 1, respectively). At 1 year, RFC patients had significantly
      better Tegner score (4.1 +/- 0.8 vs. 2.8 +/- 0.6, P < 0.001) and KOOS domain
      scores for pain, symptoms, ADL, QOL, respectively (81.1 +/- 8, vs. 59.4 +/- 12.8;
      80.7 +/- 7.5 vs. 59.6 +/- 7.5; 81.5 +/- 6.5 vs. 60.1 +/- 6.9; 80 +/- 10 vs. 61.3
      +/- 12.5; P < 0.001) than MSD patients. Significantly fewer RFC patients (2% vs
      23%, p = 0.026) reported using NSAIDS for knee pain at 1 year. Patients
      undergoing radiofrequency-based chondroplasty for ICRS grade III medial femoral
      condyle chondral lesions in conjunction with partial meniscectomy had
      significantly better clinical outcomes through 1 year than patients with similar
      pathology receiving chondral debridement using the mechanical shaver.

PMID- 18327568
TI  - Mechanism of Coomassie brilliant blue G-250 binding to proteins: a hydrophobic
      assay for nanogram quantities of proteins.
AB  - We investigated the mechanism of Coomassie brilliant blue G-250 (CBB) binding to
      proteins in order to develop a protein assay with the maximum possible
      sensitivity. We found that the neutral ionic species of CBB binds to proteins by
      a combination of hydrophobic interactions and heteropolar bonding with basic
      amino acids. On the basis of these findings, we developed a very sensitive
      hydrophobic assay for proteins (at the nanogram level) using the hydrophobic
      reagents ammonium sulfate and trichloroacetic acid under pH conditions that
      increase neutral species concentration in the assay reagent in order to enhance
      the binding of more CBB dye molecules per protein molecule than in previous CBB
      based assays.

PMID- 18327569
TI  - Universal liposomes: preparation and usage for the detection of mRNA.
AB  - Dye-encapsulating liposomes can serve as signaling reagents in biosensors and
      biochemical assays in place of enzymes or fluorophores. Detailed here is the use
      and preparation of streptavidin-coupled liposomes which offer a universal
      approach to biotinylated target detection. The universal approach provides two
      advantages, i.e. only one type of liposome is necessary despite varying target
      and probe sequences and the hybridization event can take place in the absence of
      potential steric hindrance occurring from liposomes directly conjugated to
      probes. One objective of this work was to optimize the one-step conjugation of
      SRB-encapsulating liposomes to streptavidin using EDC. Liposome, EDC,
      streptavidin concentrations, and reaction times were varied. The optimal coupling
      conditions were found to be an EDC:carboxylated lipid:streptavidin molar ratio of
      600:120:1 and a reaction time of 15 min. The second goal was to utilize these
      liposomes in sandwich hybridization microtiter plate-based assays using
      biotinylated reported probes as biorecognition elements. The assay was optimized
      in terms of probe spacer length, probe concentration, liposome concentration, and
      streptavidin coverage. Subsequently, the optimized protocol was applied to the
      detection of DNA and RNA sequences. A detection limit of 1.7 pmol L(-1) and an
      assay range spanning four orders of magnitude (5 pmol L(-1)-50 nmol L(-1)) with a
      coefficient of variation </=5.8% was found for synthetic DNA. For synthetic RNA
      the LOQ was half that of synthetic DNA. A comparison was made to alkaline
      phosphatase-conjugated streptavidin for detection which yielded a limit of
      quantitation approximately 80 times higher than that for liposomes in the same
      system. Thus, liposomes and the optimized sandwich hybridization method are well
      suited for detecting single-stranded nucleic acid sequences and compares
      favorably to other sandwich hybridization schemes recently described in the
      literature. The assay was then used successfully for the clear detection of mRNA
      amplified by nucleic acid sequence-based amplification (NASBA) isolated from as
      little as one Cryptosporidium parvum oocyst. The detection of mRNA from oocysts
      isolated from various water sample types using immunomagnetic separation was also
      assessed. Finally, to prove the wider applicability and sensitivity of this
      universal method, RNA amplified from the atxA gene of Bacillus anthracis was
      detected when the input to the preceding NASBA reaction was as low as 1.2 pg.
      This highly sensitive liposome-based microtiter plate assay is therefore a
      platform technology allowing for high throughput and wide availability for
      routine clinical and environmental laboratory applications.

PMID- 18327570
TI  - Application of methyl parathion hydrolase (MPH) as a labeling enzyme.
AB  - Methyl parathion hydrolase (MPH) is an enzyme that catalyzes the degradation of
      methyl parathion, generating a yellow product with specific absorption at 405 nm.
      The application of MPH as a new labeling enzyme was illustrated in this study.
      The key advantages of using MPH as a labeling enzyme are as follows: (1) unlike
      alkaline phosphatase (AP), horseradish peroxidase (HRP), and glucose oxidase
      (GOD), MPH is rarely found in animal cells, and it therefore produces less
      background noise; (2) its active form in solution is the monomer, with a
      molecular weight of 37 kDa; (3) its turnover number is 114.70 +/- 13.19 s(-1),
      which is sufficiently high to yield a significant signal for sensitive detection;
      and (4) its 3D structure is known and its C-terminal that is exposed to the
      surface can be easily subjected to the construction of genetic engineering
      monocloning antibody-enzyme fusion for enzyme-linked immunosorbent assay (ELISA).
      To demonstrate its utility, MPH was ligated to an single-chain variable fragment
      (scFv), known as A1E, against a white spot syndrome virus (WSSV) with the
      insertion of a [-(Gly-Ser)(5)-] linker peptide. The resulting fusion protein MPH
      A1E possessed both the binding specificity of the scFv segment and the catalytic
      activity of the MPH segment. When MPH-A1E was used as an ELISA reagent, 25 ng
      purified WSSV was detected; this was similar to the detection sensitivity
      obtained using A1E scFv and the HRP/Anti-E Tag Conjugate protocol. The fusion
      protein also recognized the WSSV in 1 microL hemolymph from an infected shrimp
      and differentiated it from a healthy shrimp. [figure: see text]

PMID- 18327571
TI  - Health risks of tattoo colors.

PMID- 18327572
TI  - Development, standardization and refinement of procedures for evaluating effects
      of endocrine active compounds on development and sexual differentiation of
      Xenopus laevis.
AB  - Xenopus laevis has been introduced as a model to study effects of endocrine
      active compounds (EAC) on development and sexual differentiation. However,
      variable and inconsistent data have raised questions about the reliability of the
      test methods applied. The current study was conducted in two laboratories to
      develop, refine, and standardize procedures and protocols. Larvae were exposed in
      flow-through systems to 17beta-estradiol (E2), at concentrations from 0.2 to 6.0
      microg E2 L(-1) in Experiment 1A, and 0.015 to 2.0 microg E2 L(-1) in Experiment
      1B. In both studies survival (92%, 99%) and percentage of animals that completed
      metamorphosis (97%, 99%) indicated reproducible biological performance.
      Furthermore, minor variations in husbandry led to significant differences in
      snout-to-vent length, weight, and gonad size. In Experiment 1A, almost complete
      feminization occurred in all E2 treatment groups whereas a concentration response
      was observed in Experiment 1B resulting in an EC(50) of 0.12 microg E2 L(-1). The
      final verified protocol is suitable for determining effects of EAC on development
      and sexual differentiation in X. laevis.

PMID- 18327573
TI  - Stalked protozoa identification by image analysis and multivariable statistical
      techniques.
AB  - Protozoa are considered good indicators of the treatment quality in activated
      sludge systems as they are sensitive to physical, chemical and operational
      processes. Therefore, it is possible to correlate the predominance of certain
      species or groups and several operational parameters of the plant. This work
      presents a semiautomatic image analysis procedure for the recognition of the
      stalked protozoa species most frequently found in wastewater treatment plants by
      determining the geometrical, morphological and signature data and subsequent
      processing by discriminant analysis and neural network techniques. Geometrical
      descriptors were found to be responsible for the best identification ability and
      the identification of the crucial Opercularia and Vorticella microstoma
      microorganisms provided some degree of confidence to establish their presence in
      wastewater treatment plants.

PMID- 18327574
TI  - Compensatory postural adaptations during continuous, variable amplitude
      perturbations reveal generalized rather than sequence-specific learning.
AB  - We examined changes in the motor organization of postural control in response to
      continuous, variable amplitude oscillations evoked by a translating platform and
      explored whether these changes reflected implicit sequence learning. The platform
      underwent random amplitude (maximum +/- 15 cm) and constant frequency (0.5 Hz)
      oscillations. Each trial was composed of three 15-s segments containing seemingly
      random oscillations. Unbeknownst to participants, the middle segment was repeated
      in each of 42 trials on the first day of testing and in an additional seven
      trials completed approximately 24 h later. Kinematic data were used to determine
      spatial and temporal components of total body centre of mass (COM) and joint
      segment coordination. Results showed that with repeated trials, participants
      reduced their magnitude of COM displacement, shifted from a COM phase lag to a
      phase lead relative to platform motion and increased correlations between
      ankle/platform motion and hip/platform motion as they shifted from an ankle
      strategy to a multi-segment control strategy involving the ankle and hip.
      Maintenance of these changes across days provided evidence for learning. Similar
      improvements for the random and repeated segments, indicated that participants
      did not exploit the sequence of perturbations to improve balance control. Rather,
      the central nervous system may have been tuning into more general features of
      platform motion. These findings provide important insight into the
      generalizabilty of improved compensatory balance control with training.

PMID- 18327575
TI  - The effects of neuromuscular fatigue on task performance during repetitive goal
      directed movements.
AB  - Proper movement timing is essential to the successful execution of many motor
      tasks and may be adversely affected by muscle fatigue. This study quantified how
      muscle fatigue affected task performance during a repetitive upper extremity
      task. A total of 14 healthy young adults pushed a low load back and forth along a
      low-friction horizontal track in time with a metronome until volitional
      exhaustion. Kinematic, force, and electromyography (EMG) data were measured
      continuously throughout the task. The first and last 3.5 min were analyzed to
      represent "early" and "late" fatigue. Means and standard deviations of movement
      distance, speed, and timing errors were computed. We also decomposed variations
      in movement distance and speed into deviations that directly affected achieving
      the task goal and those that did not, by identifying the goal equivalent manifold
      (GEM) of all valid solutions to this task. Detrended fluctuation analysis was
      used to quantify the temporal persistence in each time series. Principle
      components analysis provided a direct measure of alignment with the GEM. Median
      power frequencies of the EMG significantly decreased in six of the nine muscles
      tested indicating that subjects did fatigue. However, there were no differences
      in the means or variability of movement distance, speed, or timing errors. Thus,
      subjects maintained overall performance despite fatigue. Subjects applied
      slightly higher peak handle forces when they were fatigued (P = 0.032). Muscle
      fatigue caused significant reductions in the temporal persistence of movement
      speed (P = 0.037) and timing errors (P = 0.046), indicating that subjects
      corrected errors more quickly when fatigued. Mean deviations and variability
      perpendicular to the GEM were much smaller than variability along the GEM (P <
      0.001). Deviations perpendicular to the GEM were also corrected much more rapidly
      than those along the GEM (P < 0.001). Subjects aligned themselves very closely
      (<+/-7 degrees ), but not exactly (P < 0.001), with the GEM. These measures were
      not significantly affected by muscle fatigue. Overall, these results indicated
      that subjects altered their biomechanical movement patterns in response to muscle
      fatigue, but did so in a way that specifically preserved the goal relevant
      features of task performance.

PMID- 18327576
TI  - Intussusception mimicking rectal prolapse.
AB  - We report a 10-week-old boy with a prolapsing colocolic intussusception mimicking
      rectal prolapse. Rectal prolapse of ileocolic intussusception has been well
      described, but colocolic intussusception presenting as rectal prolapse is unique.

PMID- 18327577
TI  - Laws' masks descriptors applied to bone texture analysis: an innovative and
      discriminant tool in osteoporosis.
AB  - OBJECTIVE: The objective of this study was to explore Laws' masks analysis to
      describe structural variations of trabecular bone due to osteoporosis on high
      resolution digital radiographs and to check its dependence on the spatial
      resolution. Laws' masks are well established as one of the best methods for
      texture analysis in image processing and are used in various applications, but
      not in bone tissue characterisation. This method is based on masks that aim to
      filter the images. From each mask, five classical statistical parameters can be
      calculated. MATERIALS AND METHODS: The study was performed on 182 healthy
      postmenopausal women with no fractures and 114 age-matched women with fractures
      [26 hip fractures (HFs), 29 vertebrae fractures (VFs), 29 wrist fractures (WFs)
      and 30 other fractures (OFs)]. For all subjects radiographs were obtained of the
      calcaneus with a new high-resolution X-ray device with direct digitisation (BMA,
      D3A, France). The lumbar spine, femoral neck, and total hip bone mineral density
      (BMD) were assessed by dual-energy X-ray absorptiometry. RESULTS: In terms of
      reproducibility, the best results were obtained with the TRE5E5 mask, especially
      for three parameters: "mean", "standard deviation" and "entropy" with,
      respectively, in vivo mid-term root mean square average coefficient of variation
      (RMSCV)%= 1.79, 4.24 and 2.05. The "mean" and "entropy" parameters had a better
      reproducibility but "standard deviation" showed a better discriminant power.
      Thus, for univariate analysis, the difference between subjects with fractures and
      controls was significant (P<10(-3)) and significant for each fracture group
      independently (P<10(-4) for HF, P=0.025 for VF and P< 10(-3) for OF). After
      multivariate analysis with adjustment for age and total hip BMD, the difference
      concerning the "standard deviation" parameter remained statistically significant
      between the control group and the HF and VF groups (P<5 x 10(-5), and P=0.04,
      respectively). No significant correlation between these Laws' masks parameters
      and BMD was obtained. In addition, this study showed the dependence of Laws'
      masks parameters on image resolution, which confirms the necessity to perform
      Laws' textural measurement on high-resolution images. CONCLUSION: The
      reproducibility and discriminant power of the Laws' masks analysis has been
      demonstrated on bone images; thus, this method constitutes a promising routine
      technique for the determination of osteoporosis fracture risk from radiographs.

PMID- 18327578
TI  - Superficial acral fibromyxoma: a report of two cases with radiological findings.
AB  - Superficial acral fibromyxoma is a recently described soft tissue neoplasm with a
      predilection for the tips of the fingers and toes. As such it must be included in
      the radiological differential diagnosis of soft tissue lesions eroding bone in
      this location. The radiological features of this distinctive tumour have not so
      far been described. We report two cases with radiological and histopathological
      features.

PMID- 18327579
TI  - Combination of two fiber-mutant adenovirus vectors, one encoding the chemokine
      FKN and another encoding cytokine interleukin 12, elicits notably enhanced anti
      tumor responses.
AB  - For achieving optimal cancer immunotherapy, it is anticipated that both the
      activation and infiltration of immune cells into tumor are indispensable. In the
      present study, fiber-mutant adenovirus vectors (Ad) encoding chemokine FKN,
      (AdRGD-FKN), and cytokine interleukin 12, (AdRGD-IL-12), were constructed. The in
      vivo gene expression of AdRGD was confirmed and the combination of both FKN and
      IL-12 encoding Ad elicited synergistic anti-tumor activity in ovarian carcinoma,
      which induced tumor regression in all tumor-bearing mice, while using FKN alone
      did not show notable tumor-suppressive effect. The treatment with both IL-12 and
      FKN induced long-term specific immunity against OV-HM tumors in tumor-rejected
      mice. The results of immunohistochemical staining for CD3+ and perforin-positive
      cells suggested that the failure of using FKN alone was because of the
      inactivation of infiltrated immune cells. In contrast, cotransduction with IL-12
      and FKN could induce more activated tumor-infiltrating immune cells than that
      transducted with FKN or IL-12 alone. The results indicated that using both
      chemokine and cytokine might be a powerful tool and a promising way for effective
      cancer immunotherapy.

PMID- 18327580
TI  - Cooperation of adenosine and prostaglandin E2 (PGE2) in amplification of cAMP-PKA
      signaling and immunosuppression.
AB  - INTRODUCTION: We hypothesize that adenosine and PGE2 could have a complementary
      immunosuppressive effect that is mediated via common cAMP-PKA signaling.
      MATERIALS AND METHODS: To test this hypothesis, the effect of adenosine and PGE2
      on the cytotoxic activity and cytokine production of lymphokine activated killer
      (LAK) cells was investigated. RESULTS: PGE2 and adenosine inhibited LAK cells
      cytotoxic activity and production of INF-gamma, GM-CSF and TNF-alpha. In
      combination they showed substantially higher inhibition than each modality used
      alone. Using agonists and antagonists specific for PGE2 and adenosine receptors
      we found that cooperation of PGE2 and adenosine in their inhibitory effects are
      mediated via EP2 and A2A receptors, respectively. LAK cells have 35-fold higher
      expression of EP2 than A2A. Combined PGE2 and adenosine treatment resulted in
      augmentation of cAMP production, PKA activity, CREB phosphorylation and
      inhibition of Akt phosphorylation. Wortmannin and LY294002 enhanced the
      suppressive effects of adenosine and PGE2. In contrast, Rp-8-Br-cAMPS, an
      inhibitor of PKA type I blocked their immunosuppressive effects, suggesting that
      the inhibitory effects of PGE2 and adenosine are mediated via common pathway with
      activation of cAMP-PKA and inhibition of Akt. CONCLUSION: In comparison to other
      immunosuppressive molecules (TGF-beta and IL-10), adenosine and PGE2 are unique
      in their ability to inhibit the executive function of highly cytotoxic cells.
      High intratumor levels of adenosine and PGE2 could protect tumor from immune
      mediated destruction by inactivation of the tumor infiltrating functionally
      active immune cells.

PMID- 18327581
TI  - Immune, endocrine, and behavioral precursors to breast cancer recurrence: a case
      control analysis.
AB  - BACKGROUND: A period of tumor growth precedes the clinical detection of breast
      cancer recurrence. We explore immune, endocrine, and behavioral parameters during
      this period. METHODS: We conducted a phase III clinical trial in which women with
      surgically treated stage II/III breast cancer (N = 227) were randomized to
      receive a psychological intervention or assessment-only and then regularly
      assessed for 10 years. Patients who recurred (R, n = 48) were matched with
      patients remaining disease-free (DF, n = 48) on demographic and prognostic
      characteristics, treatment, and duration of disease-free follow-up. Data at three
      assessment points, occurring, on average, 17, 11, and 4 months before the
      recurrence was detected clinically, with equivalent time points for the disease
      free group, were examined. Mixed-effects models tested for group differences in
      immune cell counts and function as well as endocrine and behavioral parameters.
      RESULTS: In the 17 months prior to recurrence detection, patients exhibited
      higher white blood cell count, neutrophil, lymphocyte, and natural killer cell
      counts, relative to DF patients. R patients also showed higher cortisol, worse
      physical functioning, fatigue, and quality of life. Follow-up analyses showed
      patients with local recurrences to differ from those with distant recurrence,
      with the former exhibiting elevated natural killer cell cytotoxicity, lymphocyte
      proliferative response, fatigue, pain, and emotional distress (depression,
      anxiety), and the latter exhibiting higher neutrophil, lymphocyte, and natural
      killer cell counts. CONCLUSION: Patients who would recur showed reliable
      biobehavioral alterations more than a year prior to their diagnosis. This novel
      observation may contribute to our understanding of the disease relapse processes.

PMID- 18327582
TI  - What is the significance of a positive Propionibacterium acnes culture around a
      joint replacement?
AB  - The purpose of this study was to show the significance of a positive
      Propionibacterium acnes sample around a joint replacement. Records from the
      microbiology laboratory data over a 3-year period were reviewed to identify
      patients with prosthetic joints from whom Propionibacterium acnes was isolated at
      least once. The medical records of all those patients were retrieved and the
      demographic, clinical, microbiological and haematological data were collected and
      examined. The preoperative values of erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) were recorded. Fifty patients underwent a routine revision
      of a joint arthroplasty; six patients had a joint aspiration. Only one patient
      had further revision surgery for infection. The preoperative values of ESR and
      CRP were very variable. The presence of a positive sample around a joint
      arthroplasty is of uncertain significance. Further studies are needed in order to
      establish uniform criteria for the diagnosis of infection caused by
      Propionibacterium acnes.

PMID- 18327583
TI  - High prevalence of occult hepatitis B virus infection in patients with B cell non
      Hodgkin's lymphoma.
AB  - Several reports recently found that patients with B cell non-Hodgkin's lymphoma
      (NHL) had a higher carrier rate of hepatitis B surface antigen (HBsAg). The
      current study aimed to examine the hepatitis B virus (HBV) infection status of
      NHL patients in Taiwan, an HBV-endemic area. Serum HBV and serum hepatitis C
      virus were measured in 471 NHL patients and 1,013 non-lymphoma cancer patients
      enrolled between February 2000 and March 2007. Furthermore, nested polymerase
      chain reaction of HBV-DNA was used to examine the sera from selected patients in
      these two populations and healthy volunteers for the presence of occult HBV
      infection. The infection rates (as indicated by the rates of HBsAg and occult
      HBV) were compared between different groups. There was a higher incidence of HBV
      infection in B cell NHL patients (23.5%), especially patients with diffuse large
      B lymphoma, than solid tumor patients (15.6%, P = 0.001). Among HbsAg-negative
      patients, those with B cell NHL had a higher prevalence of occult HBV infection
      (6%) than those with non-lymphoma solid tumors and healthy volunteers, 0% and
      0.9%, respectively (P = 0.005). B cell NHL patients, even HBsAg-negative B cell
      NHL patients, but not T cell NHL patients, have a higher incidence of HBV
      infection than patients with solid tumors. Our findings support the etiologic
      role of HBV infection in B cell NHL.

PMID- 18327584
TI  - Association between HFE 187 C>G (H63D) mutation and early-onset familial
      Alzheimer's disease PSEN-1 839A>C (E280A) mutation.

PMID- 18327585
TI  - CD8 expression in B-cell non-Hodgkin's lymphomas.

PMID- 18327586
TI  - Epidermal growth factor receptor serum (sEGFR) level may predict response in
      patients with EGFR-positive advanced colorectal cancer treated with gefitinib?
AB  - PURPOSE: Epidermal growth factor receptor-overexpression reported in colorectal
      cancer, justifies therapeutic use of EGFR-inhibitors. We have recently conducted
      a phase II study in 57 patients with EGFR-positive advanced colorectal cancer
      (ACC) who received gefitinib-FOLFOX6 followed by gefitinib-single agent as
      maintenance. Main biological objective was to assess sEGFR as surrogate marker of
      tyrosine kinase inhibition and as predictor of response. METHODS: sEGFR,
      evaluated by quantitative ELISA, was investigated as predictive factor both
      taking into account the basal value only, and its whole pattern over time. sEGFR
      was collected at baseline and at every 2-months assessment in 42 cases. Thirty
      three patients reported CR/PR as best objective response (BOR), while nine showed
      SD/PD. RESULTS: Retrospectively, on average, the sEGFR values reported by both
      responders (CR/PR) and not responders (SD/PD) were already different at baseline
      (49.4 +/- 6.2 and 42.4 +/- 8.4 ng/ml respectively). This difference was
      statistically significant (p = 0.042). Although sEGFR trend over time confirmed
      the basal difference (p = 0.032), this result should be taken with caution, due
      to the small number of patients reporting EGFR values besides the basal one.
      CONCLUSIONS: Higher sEGFR at baseline was associated to BOR and may be considered
      a significant predictor of outcome in patients with ACC.

PMID- 18327587
TI  - A phase I and pharmacologic study of the combination of bortezomib and pegylated
      liposomal doxorubicin in patients with refractory solid tumors.
AB  - PURPOSE: Pre-clinical studies combining the proteasome inhibitor bortezomib with
      anthracyclines have shown enhanced anti-tumor activity. We conducted a phase I
      trial of bortezomib and pegylated liposomal doxorubicin (PLD) in patients with
      refractory solid tumors. METHODS: Patients received bortezomib, 0.9-1.5 mg/m(2),
      on days 1, 4, 8, and 11 of every 21-day cycle, along with PLD, 30 mg/m(2), on day
      4. The goals were to determine the dose limiting toxicity (DLT) and maximum
      tolerated dose (MTD), and to investigate pharmacokinetic and pharmacodynamic
      interactions of the combination. RESULTS: A total of 37 patients with four median
      prior therapies were treated. Frequent grade 1-2 toxicities included fatigue,
      nausea, thrombocytopenia, anemia, neutropenia, constipation, myalgias, and
      peripheral neuropathy. DLTs included grade 3 nausea and vomiting in 1 of 6
      patients receiving bortezomib at 1.2 mg/m(2), and grade 3 nausea, vomiting, and
      diarrhea in 1 of 6 patients receiving bortezomib at 1.5 mg/m(2). Grade 3
      toxicities in later cycles included hand-foot syndrome, thrombocytopenia, anemia,
      neutropenia, nausea, diarrhea, and abdominal pain. Because of frequent dose
      delays, dose-reductions, and gastrointestinal toxicity at the 1.4 and 1.5 mg/m(2)
      levels, bortezomib at 1.3 mg/m(2) and PLD at 30 mg/m(2) are recommended for
      further testing. Among 19 patients with breast cancer, four had evidence of a
      clinical benefit. Pharmacokinetic and pharmacodynamic studies did not show any
      significant interactions between the two drugs. CONCLUSIONS: A regimen of
      bortezomib, 1.3 mg/m(2) on days 1, 4, 8, and 11 with PLD, 30 mg/m(2), on day 4 of
      a 21-day cycle, was safe in this study, and merits further investigation.

PMID- 18327588
TI  - Characterization of MYR1, a dosage suppressor of YPT6 and RIC1 deficient mutants.
AB  - Membrane traffic is tightly regulated and the Rab protein family of small GTPases
      plays a central role in this regulation. One member of this family is the
      Saccharomyces cerevisae protein Ypt6. To search for new genes interacting with
      Ypt6-related pathways, we performed a genetic screen for high copy suppressors of
      ypt6Delta temperature sensitivity at 35 degrees C. Among the suppressors, MYR1
      was also able to suppress the temperature sensitive mutant lacking Ric1, a
      subunit of the Ypt6 guanine exchanging factor complex Ric1/Rgp1. Myr1 is
      characterized by a coiled coil region and a GYF domain, a protein module binding
      proline-rich sequences. Myr1 is able to bind membranes but is also associated
      with larger structures insoluble in Triton X-100. By immunofluorescence, Myr1
      shows a network-like pattern as well as small foci. Overexpression of Myr1
      influences nuclear envelope morphology and high levels are lethal. This lethality
      is rescued when the N-terminal region, containing the GYF domain, is deleted. The
      transcription profile of a myr1Delta strain shows effects on genes involved in
      nuclear migration, Ras signalling and transcription. Taken together, these
      results suggest that Myr1 is a novel factor linked to the secretory pathway and
      important cellular regulatory mechanisms.

PMID- 18327589
TI  - UV sensitive mutations in histone H3 in Saccharomyces cerevisiae that alter
      specific K79 methylation states genetically act through distinct DNA repair
      pathways.
AB  - Chromatin serves as a regulator of various nuclear processes, with post
      translational modifications of histone proteins serving as modulators to
      influence chromatin function. We have previously shown that histone H3 K79
      methylation is important for repair of UV-induced DNA damage in Saccharomyces
      cerevisiae, acting through multiple repair pathways. To evaluate the potential
      role of distinct K79 methylation states in DNA repair, we identified four
      mutations in histone H3 that confer sensitivity to UV, each of which also has a
      distinct effect on specific K79 methylation states. Epistasis analyses indicate
      that each mutation exerts its phenotypic effects through distinct subsets of the
      various DNA damage response pathways, suggesting the existence of discrete roles
      for histone H3 in DNA damage checkpoint and repair pathways. Furthermore, we find
      that the distribution of K79 methylation states is altered by mutation of the
      acetylatable N terminal lysines in histone H4. The combined results suggest that
      K79 methylation states may be modulated in response to UV damage via a trans
      histone regulatory pathway, and that distinct methylation states may provide a
      means of coordinating specific DNA repair and damage checkpoint pathways.

PMID- 18327590
TI  - Competitive interaction between two functional S-haplotypes confer self
      compatibility on tetraploid Chinese cherry (Prunus pseudocerasus Lindl. CV.
      Nanjing Chuisi).
AB  - Self-incompatibility (SI) has been studied extensively at the molecular level in
      Solanaceae, Rosaceae and Scrophulariaceae, all of which exhibit gametophytic self
      incompatibility (GSI). In the present study, four PpsS-haplotypes (Prunus
      pseudocerasus S-haplotypes) comprising at least two genes, i.e., PpsS-RNase (P.
      pseudocerasus S-RNase) and PpsSFB (P. pseudocerasus S-haplotype-specific F-box)
      have been successfully isolated in tetraploid P. pseudocerasus Lindl. CV. Nanjing
      Chuisi ("NC") which exhibited self-compatibility (SC), and its S-genotype was
      determined as S-1/S-3'/S-5/S-7. These PpsS-RNases, which were expressed
      exclusively in style, shared the typical structural features with S-RNases from
      other Prunus species exhibiting GSI. All PpsSFBs showed similar structure
      characteristics of SFBs from other Prunus species, and matched with the necessary
      conditions for pollen S-determinant. No mutations leading to dysfunction of S
      haplotype were found in their full-length c-DNA sequences, except for PpsS-3'
      haplotype which was not amplified by PCR. These four S-haplotypes complied with
      tetrasomic inheritance. Diploid pollen grains with S-genotypes S-7/S-1, S-7/S-5
      and S-1/S-5 can grow the full length of the style after self-pollination, while
      pollen grains with S-3'/S-7, S-3'/S-1 and S-3'/S-5 cannot. These results suggest
      that PpsS-haplotypes-1, -5 and -7 are functional, and that competitive
      interaction between two of them confer self-compatibility on cultivar "NC".
      Furthermore, in terms of recognition specificity, diploid pollen grains carrying
      PpsS-3'-haplotype are equal to monoploid pollen grains carrying the other
      functional S-haplotype.

PMID- 18327591
TI  - Morphometric and biochemical characterization of red beet (Beta vulgaris L.)
      hairy roots obtained after single and double transformations.
AB  - It is known that T-DNA of Agrobacterium rhizogenes affects processes of plant
      development and activates the synthesis of secondary metabolites in transformed
      plant cells. In the present investigation, we provide evidence that different
      strains of A. rhizogenes significantly affect morphometric, morphological and
      functional characteristics of hairy roots of red beet (Beta vulgaris L.).
      Infection with four strains of A. rhizogenes (A4, A 2/83, A 20/83 and LMG-150)
      resulted in ten clones of hairy roots, which were named accordingly as A4(1),
      A4(2), A4(3), A 2/83(1), A 2/83(2), A 2/83(3), A 20/83(1), A 20/83(2), A 20/83(3)
      and LMG-150. Their growth characteristics, pigment content, levels of endogenous
      auxin and T-DNA copy number showed significant differences probably due to the
      physiological status of the host cell rather than the T-DNA copy number. Although
      A 2/83 showed highest hairy root induction capacity, the best hairy root clone
      was obtained with strain LMG-150 that produced highest biomass and pigments. In
      this root clone, the enzyme peroxidase was found involved in altering the
      endogenous auxin pool. When root clone LMG-150 was re-transformed to insert
      additional individual rol genes, two double transformed clones were obtained, one
      for rolABC and the other for rolC gene where the former produced higher biomass
      and betalaine than the latter. Despite the established fact that rol genes of T
      DNA influence endogenous phytohormones, no direct correlation among the single
      transformants and the double transformants was found. This is the first report,
      in our knowledge, where a hairy root clone has been used to obtain double
      transformants.

PMID- 18327592
TI  - Agrobacterium tumefaciens-mediated transformation of poinsettia, Euphorbia
      pulcherrima, with virus-derived hairpin RNA constructs confers resistance to
      Poinsettia mosaic virus.
AB  - Agrobacterium-mediated transformation for poinsettia (Euphorbia pulcherrima
      Willd. Ex Klotzsch) is reported here for the first time. Internode stem explants
      of poinsettia cv. Millenium were transformed by Agrobacterium tumefaciens, strain
      LBA 4404, harbouring virus-derived hairpin (hp) RNA gene constructs to induce RNA
      silencing-mediated resistance to Poinsettia mosaic virus (PnMV). Prior to
      transformation, an efficient somatic embryogenesis system was developed for
      poinsettia cv. Millenium in which about 75% of the explants produced somatic
      embryos. In 5 experiments utilizing 868 explants, 18 independent transgenic lines
      were generated. An average transformation frequency of 2.1% (range 1.2-3.5%) was
      revealed. Stable integration of transgenes into the poinsettia nuclear genome was
      confirmed by PCR and Southern blot analysis. Both single- and multiple-copy
      transgene integration into the poinsettia genome were found among transformants.
      Transgenic poinsettia plants showing resistance to mechanical inoculation of PnMV
      were detected by double antibody sandwich enzyme-linked immunosorbent assay (DAS
      ELISA). Northern blot analysis of low molecular weight RNA revealed that
      transgene-derived small interfering (si) RNA molecules were detected among the
      poinsettia transformants prior to inoculation. The Agrobacterium-mediated
      transformation methodology developed in the current study should facilitate
      improvement of this ornamental plant with enhanced disease resistance, quality
      improvement and desirable colour alteration. Because poinsettia is a non-food,
      non-feed plant and is not propagated through sexual reproduction, this is likely
      to be more acceptable even in areas where genetically modified crops are
      currently not cultivated.

PMID- 18327593
TI  - Overexpression of AtMHX in tobacco causes increased sensitivity to Mg2+, Zn2+,
      and Cd2+ ions, induction of V-ATPase expression, and a reduction in plant size.
AB  - AtMHX is a vacuolar transporter encoded by a single gene in Arabidopsis.
      Electrophysiological analysis showed that it exchanges protons with Mg(2+),
      Zn(2+), and Fe(2+) ions. The physiological impact of AtMHX was examined so far
      only in tissue-culture grown seedlings of tobacco plants overexpressing this
      transporter. Here we investigated the impact of AtMHX on growth, response to
      different metals, and metal accumulation of mature tobacco plants, as well as
      Arabidopsis plants in which we overexpressed this transporter. The analyses were
      carried out in hydroponic growth-systems, in which the mineral composition could
      be effectively controlled, and the metal content of roots could be examined.
      Transformed tobacco plants showed necrotic lesions and apical burnings upon
      growth with increased levels of Mg(2+), Zn(2+), and Cd(2+) ions. This suggested
      that AtMHX can carry in planta not only Mg(2+) and Zn(2+) ions, as previously
      deduced based on observations in tissue-culture, but also Cd(2+) ions.
      Transformed plants of both tobacco and Arabidopsis showed a reduction in plant
      size. However, the overall response of Arabidopsis to AtMHX overexpression was
      minor. No change was detected in the mineral content of any organ of the
      transgenic tobacco or Arabidopsis plants. The necrotic lesions in tobacco
      resembled those seen in plants with perturbed proton balancing, raising the
      assumption that AtMHX can affect the proton homeostasis of cells. In agreement
      with this assumption, the transformed tobacco plants had increased expression and
      activity of the vacuolar H(+)-ATPase. The relative significance of AtMHX for
      metal and proton homeostasis still has to be elucidated.

PMID- 18327594
TI  - Radiology report turnaround: expectations and solutions.
AB  - The ultimate work product of a radiology department is a finalized radiology
      report. Radiology stakeholders are now demanding faster report turnaround times
      (RTAT) and anything that delays delivery of the finalized report will undermine
      the value of a radiology department. Traditional reporting methods are inherently
      inefficient and the desire to deliver fast RTAT will always be challenged. It is
      only through the adoption of an integrated radiology information system
      (RIS)/picture archiving and communication system (PACS) and voice recognition
      (VR) system that RTAT can consistently meet stakeholder expectations. VR systems
      also offer the opportunity to create standardized, higher quality reports.

PMID- 18327595
TI  - Three-dimensional orientation in desert ants: context-independent memorisation
      and recall of sloped path segments.
AB  - Desert ants (Cataglyphis fortis) navigate by a combination of path integration
      and landmark-based route memories. Their ability to correct sloped path segments
      to their ground distances enables them to orientate accurately even in undulating
      terrain. In this study, we tested whether or not ants incorporate vertical
      components of an itinerary into their route memory in similar ways as they do
      with visual landmarks and horizontal changes of direction. In two separate
      experiments, we trained desert ants to walk over artificial hills and later
      tested their acceptance of slopes within novel contexts. In the first paradigm,
      ants had to traverse a hill only on their outbound run, but not on their
      homebound trip. In a follow-up experiment, we confronted ramp-trained animals
      with descents in a completely new temporal and spatial context. The animals
      transferred their newly acquired acceptance of slopes from the outbound to the
      homebound run as well as to novel foraging trips. Cataglyphis obviously
      dissociates the experience of sloped path segments from the original context in
      which they appeared, thus reducing their significance as a navigational aid.

PMID- 18327596
TI  - Rebampide enema therapy as a treatment for patients with chronic radiation
      proctitis: initial treatment or when other methods of conservative management
      have failed.
AB  - INTRODUCTION: Radiation proctitis is a common complication following radiation
      therapy for pelvic malignancies. There have been no formal trials of treatment
      for radiation proctitis and a variety of methods are currently used. We assessed
      the efficacy of rebamipide enema to control symptoms and proctoscopic findings
      from radiation proctitis. MATERIALS AND METHODS: Fifteen patients with radiation
      proctitis were enrolled. Enemas containing 150 mg rebamipide per dosing were
      administered after morning bowel movement, and always prior to bedtime, twice
      daily for 4 weeks. The efficacy of treatment was assessed from clinical symptoms
      (Subjective Objective Management Analysis Scale for Rectal Toxicity) and
      endoscopic findings. RESULTS: The mean bleeding score improved from 2.67 to 0.53
      (P < 0.01). The mean symptom scores improved in those patients who had pain (0.40
      to 0.13), tenesmus (0.40 to 0.20), and stool frequency (0.27 to 0.13). The mean
      improvement in telangiectasia scores (2.13 to 0.80, P < 0.01), bleeding point
      scores (1.80 to 0.27, P < 0.01), and friable mucosa scores (1.33 to 0.20, P <
      0.01) were all statistically significant. No side effects were noted in any
      patients. CONCLUSION: Rebamipide enema therapy for radiation proctitis is a safe
      and effective treatment of radiation proctitis. We suggest the value of
      rebamipide enema in the treatment of radiation proctitis when other conservative
      management or first treatment has failed.

PMID- 18327597
TI  - Prophylaxis against thromboembolism in spinal surgery.
AB  - Thromboprophylaxis in spinal surgery is a controversial topic. In the current
      environment of risk management, it seems reasonable to review and critically
      appraise the risks and benefits of different prophylaxis methods in spinal
      surgery.

PMID- 18327598
TI  - A novel mutation in RASA1 causes capillary malformation and limb enlargement.
AB  - Capillary malformations are common vascular malformations. Several syndromes have
      been described in which CMs are present in association with limb enlargement,
      among these are Klippel-Trenaunay syndrome (KTS) and Parkes Weber syndrome (PWS).
      Mutations in the RASA1 gene have been shown to underlie the capillary
      malformation-arterio-venous malformation (CM-AVM) syndrome, sometimes presenting
      with PWS. We identified a family comprising a patient with CMs and limb
      enlargement and a number of family members with CM/CM-AVM. A novel mutation in
      RASA1 was found to underlie the disease in this case. The present results
      illustrate the extensive degree of phenotypic heterogeneity associated with
      deleterious mutations in RASA1.

PMID- 18327599
TI  - Laryngeal and hypopharyngeal obstruction in sleep disordered breathing patients,
      evaluated by sleep endoscopy.
AB  - The objectives of our study were to demonstrate the patterns and sites of the
      upper airway (UA) collapse in obstructive sleep apnea/hypopnea syndrome (OSAHS)
      patients, utilizing the sleep endoscopy technique, and to describe the technique
      and summarize our experience in a large series of patients. UA findings during
      sleep endoscopy with midazolam were examined prospectively in 55 surgical
      candidates with OSAHS. The uvulopalantine was the most common site of obstruction
      (89%), followed by the tongue base, hypopharynx and larynx (33% each), and nose
      (21%); 72% of the patients had multiple obstructions. There was a significant
      correlation between the number of obstructions and the respiratory distress index
      (RDI). Laryngeal obstruction was typically supraglottic. Hypopharyngeal
      obstruction involved concentric UA narrowing. Our findings emphasize the
      considerable rate of laryngeal and hypopharyngeal obstructions in patients with
      OSAHS and suggest that their misdiagnosis may explain at least part of the high
      surgical failure rate of UPPP for OSAHS patients. The number of obstruction sites
      correlates with respiratory distress index. Sleep endoscopy is safe and simple to
      perform.

PMID- 18327600
TI  - Hearing preservation after translabyrinthine approach performed to remove a large
      vestibular schwannoma.
AB  - We report the case of a 27-year-old woman from whom a left vestibular schwannoma
      (grade IV) was removed by a translabyrinthine approach. The initial period was
      uneventful except for a few days of vertigo. This patient had no facial paresis
      (House-Brackman grade I). She was seen 1, 3, 6 and 12 months after operation and
      reported a sensation of hearing in the left ear. The audiological studies showed
      a left medium hearing loss. At the 1-year follow-up visit, her hearing status was
      unchanged. A hearing aid was fitted and functioned satisfactory. At the 5-year
      follow-up visit, audiometry studies were unchanged. Our case demonstrated that
      some hearing preservation could be obtained even if the vestibular schwannoma was
      large and excised by a translabyrinthine approach. Hearing with the help of a
      good hearing aid allowed a satisfactory function in this case. We believe that it
      is possible to preserve some hearing after translabyrinthine approach even if no
      care was taken to preserve the membraneous labyrinth and the loss of endolymph
      and even if the vestibular schwannoma was large. However, further experimental
      studies are needed to determine and understand the mechanisms of hearing
      preservation in this case.

PMID- 18327601
TI  - Genetic profile characterization and segregation analysis of 10 X-STRs in a
      sample from Santander, Colombia.
AB  - Ten X-chromosome short tandem repeats (X-STRs: DXS8378, DXS7132, DXS9898,
      DXS6809, DXS6789, DXS101, GATA172D05, HPRTB, DXS8377, and DXS7423) were analyzed
      in a sample of unrelated individuals (108 males and 110 females) from the
      Santander Department in Colombia. In this sample, gene diversities varied between
      63.56%, for DXS8378, and 91.41%, for DXS8377. For this set of 10 X-STRs, a high
      discrimination power was obtained for both male (1 in 3 x 10(6)) and female (1 in
      9 x 10(10)) samples and a high mean exclusion chance in father/daughter duos
      (99.993%) and in father/mother/daughter trios (99.9999%), demonstrating the
      usefulness of this set of markers in forensic and kinship analysis. Hardy
      Weinberg equilibrium was tested in the female sample and no significant
      deviations were found. Pairwise analysis showed significant differences in the
      comparison with samples from Spain, Peru, and Argentina and with African American
      and Hispanic samples from New York. This same set of X-STRs was also typed in 51
      mother/father/daughter trios, 43 mother/son duos, and in a single father/daughter
      pair. In total, four mutations were observed; one at DXS7132 and at DXS6809, and
      two at DXS8377. Two mutations were paternal and one maternal; and to a fourth
      mutation, it was not possible to define its origin.

PMID- 18327602
TI  - Expression and localization of Tmie in adult rat cochlea.
AB  - Loss-of function mutations in transmembrane inner ear expressed (Tmie/TMIE) gene
      have been shown to cause deafness in mice and humans (DFNB6). However, the
      functional roles of TMIE in the cochlea remain unclear. A primary step toward the
      understanding of the role of TMIE in hearing and its dysfunction is the
      documentation of its cellular and sub-cellular location within the cochlea, the
      auditory organ. In this study, we located and determined the cellular expression
      of Tmie within the rat cochlea using a polyclonal anti-Tmie antibody. The anti
      Tmie antibody identified a specific band of 17 kDa in a variety of rat tissues by
      using Western blot analyses. The expression products of Tmie were also detected
      in the spiral limbus, spiral ligament, organ of Corti, and stria vascularis by
      immunohistochemistry analysis and RT-PCR. Our results point out the presence and
      localization of Tmie products in the cochlea of rat. Knowledge of spatial
      distribution of Tmie will provide important insight into the mechanisms that lead
      to deafness due to mutations in the TMIE gene.

PMID- 18327603
TI  - Study of the validity of a job-exposure matrix for psychosocial work factors:
      results from the national French SUMER survey.
AB  - OBJECTIVE: To construct and evaluate the validity of a job-exposure matrix (JEM)
      for psychosocial work factors defined by Karasek's model using national
      representative data of the French working population. METHODS: National sample of
      24,486 men and women who filled in the Job Content Questionnaire (JCQ) by Karasek
      measuring the scores of psychological demands, decision latitude, and social
      support (individual scores) in 2003 (response rate 96.5%). Median values of the
      three scores in the total sample of men and women were used to define high
      demands, low latitude, and low support (individual binary exposures). Job title
      was defined by both occupation and economic activity that were coded using
      detailed national classifications (PCS and NAF/NACE). Two JEM measures were
      calculated from the individual scores of demands, latitude and support for each
      job title: JEM scores (mean of the individual score) and JEM binary exposures
      (JEM score dichotomized at the median). RESULTS: The analysis of the variance of
      the individual scores of demands, latitude, and support explained by occupations
      and economic activities, of the correlation and agreement between individual
      measures and JEM measures, and of the sensitivity and specificity of JEM
      exposures, as well as the study of the associations with self-reported health
      showed a low validity of JEM measures for psychological demands and social
      support, and a relatively higher validity for decision latitude compared with
      individual measures. CONCLUSION: Job-exposure matrix measure for decision
      latitude might be used as a complementary exposure assessment. Further research
      is needed to evaluate the validity of JEM for psychosocial work factors.

PMID- 18327604
TI  - Job decision latitude as a potential modifier of the contribution of physical
      workload to poor functioning in middle-aged employees.
AB  - OBJECTIVES: It was hypothesised that job decision latitude may alleviate the
      detrimental health effect of physical workload. The objective was to test whether
      job decision latitude modifies the effect of physically demanding work on poor
      physical functioning, and whether the effects of physically demanding work and
      job decision latitude are dependent on occupational social class. METHODS: Data
      were derived from the Helsinki Health Study baseline questionnaire survey. The
      participants were employees of the City of Helsinki, Finland, aged 40-60 years.
      Functioning was measured by Short Form 36 physical component summary. Logistic
      regression models were used to analyse the data. RESULTS: The hypothesised
      modification of the effect of physical demands at work on physical functioning by
      job decision latitude could not be demonstrated. The expected interaction effect
      was observed only for the semi-professional class, and interaction of physical
      demands, decision latitude and occupational social class was not statistically
      significant. Furthermore, the effects of physically demanding work as well as low
      decision latitude were of similar magnitude in all the occupational social
      classes. CONCLUSIONS: The results suggest that for the majority of employees the
      effect of physical workload on physical functioning is independent of job
      decision latitude or occupational social class in general. Control over work
      conditions is unlikely to reduce difficulties to cope with physical demands, when
      the actual physical tasks are not changed.

PMID- 18327605
TI  - Efficacy of body ventilation system for reducing strain in warm and hot climates.
AB  - This study determined whether a torso-vest forced ambient air body ventilation
      system (BVS) reduced physiological strain during exercise-heat stress. Seven heat
      acclimated volunteers attempted nine, 2-h treadmill walks at 200 W m(-2) in three
      environments, -40 degrees C, 20% rh (HD), 35 degrees C, 75% rh (HW), and 30
      degrees C, 50% rh, (WW) wearing the Army Combat Uniform, interceptor body armor
      (IBA) and Kevlar helmet. Three trials in each environment were BVS turned on
      (BVS(On)), BVS turned off (BVS(Off)), and no BVS (IBA). In HD, BVS(On)
      significantly lowered core temperature (T (re)), heart rate (HR), mean skin
      temperature (T (sk)), mean torso skin temperature (T (torso)), thermal sensation
      (TS), heat storage (S), and physiological strain index (PSI), versus BVS(Off) and
      IBA (P < 0.05). For HW (n = 6), analyses were possible only through 60 min.
      Exercise tolerance time (min) during HW was significantly longer for BVS(On) (116
      +/- 10 min) versus BVS(Off) (95 +/- 22 min) and IBA (96 +/- 18 min) (P < 0.05).
      During HW, BVS(On) lowered HR at 60 min versus IBA, T (sk) from 30 to 60 min
      versus BVS(Off) and IBA, and PSI from 45 to 60 min versus BVS(Off) and at 60 min
      versus IBA (P < 0.05). BVS(On) changes in T (re) and HR were lower in HD and HW.
      During WW, BVS(On) significantly lowered HR, T (sk), and T (torso) versus
      BVS(Off) and IBA (P < 0.05) during late exercise. Sweating rates were
      significantly lower for BVS(On) versus BVS(Off) and IBA in both HD and WW (P <
      0.05), but not HW. These results indicate that BVS(On) reduces physiological
      strain in all three environments by a similar amount; however, in hot-dry
      conditions the BVS(Off) increases physiological strain.

PMID- 18327606
TI  - Implementation of an elaborated neuromorphic model of a biological photoreceptor.
AB  - We describe here an elaborated neuromorphic model based on the photoreceptors of
      flies and realised in both software simulation and hardware using discrete
      circuit components. The design of the model is based on optimisations and further
      elaborations to the mathematical model initially developed by van Hateren and
      Snippe that has been shown to accurately simulate biological responses in
      simulations under both steady-state and limited dynamic conditions. The model
      includes an adaptive time constant, nonlinear adaptive gain control, logarithmic
      saturation and a nonlinear adaptive frequency response mechanism. It consists of
      a linear phototransduction stage, a dynamic filter stage, two divisive feedback
      loops and a static nonlinearity. In order to test the biological accuracy of the
      model, impulses and step responses were used to test and evaluate the steady
      state characteristics of both the biological (fly) and artificial (new
      neuromorphic model) photoreceptors. These tests showed that the model has
      faithfully captured most of the essential characteristics of the insect
      photoreceptor cells. The model showed a decreasing response to impulsive stimuli
      when the background intensity was increased, indicating that the circuit adapted
      to background luminance in order to improve the overall operating range and
      better encode the contrast of the stimulus rather than luminance. The model also
      showed the same change in its frequency response characteristics as the
      biological photoreceptors over a luminance range of 70,000 cd/m(2), with the
      corner frequency of the circuit ranging from 10 to 90 Hz depending on the current
      state of adaptation. Complex naturalistic experiments have also further proven
      the robustness of the model to perform in real-world scenario. The model showed
      great correlation to the biological photoreceptors with an r (2) value exceeding
      0.83. Our model could act as an excellent platform for future experiments that
      could be carried out in scenarios where in vivo intracellular recording from
      biological photoreceptors would be impractical or impossible, or as a front-end
      for an artificial imaging system.

PMID- 18327608
TI  - Approximation of optimal surface parameterizations and the application in
      cerebral cortex mapping.
AB  - Optimal parameterizations of surface meshes are useful in the mapping and
      visualization of the cerebral cortex, the outer layer of the human brain. We
      propose two new methods to compute approximations of the optimal
      parameterizations, and apply these methods to human cortical surface meshes
      extracted from magnetic resonance images. Our methods approximate the
      parameterizations in a low-dimensional subspace spanned by the coordinate vectors
      of an initial parameterization and the low-frequency eigenvectors of a mesh
      Laplacian. This low-dimensional approximation reduces the computational
      complexity while minimizing the error.

PMID- 18327607
TI  - Pepper pectin methylesterase inhibitor protein CaPMEI1 is required for antifungal
      activity, basal disease resistance and abiotic stress tolerance.
AB  - Pectin is one of the main components of the plant cell wall that functions as the
      primary barrier against pathogens. Among the extracellular pectinolytic enzymes,
      pectin methylesterase (PME) demethylesterifies pectin, which is secreted into the
      cell wall in a highly methylesterified form. Here, we isolated and functionally
      characterized the pepper (Capsicum annuum L.) gene CaPMEI1, which encodes a
      pectin methylesterase inhibitor protein (PMEI), in pepper leaves infected by
      Xanthomonas campestris pv. vesicatoria (Xcv). CaPMEI1 transcripts are localized
      in the xylem of vascular bundles in leaf tissues, and pathogens and abiotic
      stresses can induce differential expression of this gene. Purified recombinant
      CaPMEI1 protein not only inhibits PME, but also exhibits antifungal activity
      against some plant pathogenic fungi. Virus-induced gene silencing of CaPMEI1 in
      pepper confers enhanced susceptibility to Xcv, accompanied by suppressed
      expression of some defense-related genes. Transgenic Arabidopsis CaPMEI1
      overexpression lines exhibit enhanced resistance to Pseudomonas syringae pv.
      tomato, mannitol and methyl viologen, but not to the biotrophic pathogen
      Hyaloperonospora parasitica. Together, these results suggest that CaPMEI1, an
      antifungal protein, may be involved in basal disease resistance, as well as in
      drought and oxidative stress tolerance in plants.

PMID- 18327609
TI  - Human cytomegalovirus infection and antiviral immunity in septic patients without
      canonical immunosuppression.
AB  - The human cytomegalovirus (HCMV) is a relevant pathogen in patients with
      immunosuppressive therapy; however, reactivation and subsequent recurrence occurs
      also in individuals without canonical immunosuppression as e.g., in patients with
      septic shock. Analyzing the impact of NK- and T-cell immunity on the natural
      course of HCMV infection in patients with septic shock, it became clear that the
      presence of HCMV reactive T-helper cells did not prevent the development of
      reactivation but, the control of active infection was achieved mostly by specific
      T-cells. NK-cells seemed to be dispensable for clearance of active infection in
      this patient group with long-lasting NK-cell anergy.

PMID- 18327611
TI  - Efficacy of female Culex quinquefasciatus with entomopathogenic fungus Fusarium
      pallidoroseum.
AB  - This study was conducted to isolate and identify natural entomopathogenic fungi
      from female Culex quinquefasciatus and to test their adulticidal activity. Field
      collected female C. quinquefasciatus died early and were placed on a Saboraud's
      dextrose agar plates for growth and isolation of natural entomopathogenic fungi.
      The plates were maintained in an incubator at 24+/-2 degrees C for 3 days. Four
      fungal species were isolated in two genera namely, Aspergillus and Fusarium. The
      identified fungal species were A. niger, A. flavus, A. nidulans var acristatus
      (ITCC-6327.04), and F. pallidoroseum (ITCC-6324.06). Adult bioassays were carried
      out using spore-impregnated paper in WHO-holding tubes. F. pallidoroseum was
      found to be more effective than the others. Exposure of C. quinquefasciatus to
      spores of A. flavus and A. niger for 4 h caused 5.53% and 5.51% mortality in the
      mosquitoes within a week, respectively. All the female C. quinquefasciatus were
      killed within 4 days of exposure to F. pallidoroseum at a concentration of 1.11 x
      10(10) conidia per m2. Significant difference of longevity was observed between
      the F. pallidoroseum-treated C. quinquefasciatus and control mosquitoes. The LT50
      of F. pallidoroseum was 2.08 days for 4 h exposure to C. quinquefasciatus.
      Results of the present study confirm that F. pallidoroseum is one of the
      alternative biological control agents of adult mosquitoes.

PMID- 18327610
TI  - Serum thyrotropin concentration as a biochemical predictor of thyroid malignancy
      in patients presenting with thyroid nodules.
AB  - PURPOSE: Serum thyrotropin (TSH) is a well-established growth factor for thyroid
      nodules and suppression of TSH concentrations by administering exogenous
      thyroxine may interfere with the growth of established nodules as well as the
      formation of new thyroid nodules. The aim of this study was to investigate
      whether serum TSH at presentation is a predictor of thyroid malignancy in
      patients with thyroid nodules. METHODS: A total of 565 patients without overt
      thyroid dysfunction, who presented with palpable thyroid nodule(s) between 1988
      and 2004 and underwent at least one fine-needle aspiration biopsy, were
      retrospectively evaluated. RESULTS: The final diagnostic outcome was established
      after surgery (n = 122) or after a minimum of 1-year clinical follow-up period.
      Higher rates of malignancy were observed in patients with serum TSH in the upper
      tertile of the normal range (P = 0.026). Binary logistic regression analysis
      revealed significantly increased adjusted odds ratios for the diagnosis of
      malignancy in patients with serum TSH 1.5-4.0 mIU/l when compared to those with
      either TSH 0.4-0.8 mIU/l (P = 0.005) or TSH 0.9-1.4 mIU/l (P = 0.007).
      CONCLUSIONS: The risk of malignancy in thyroid nodules increases in parallel with
      TSH concentrations within the normal range. TSH concentration at presentation is
      an independent predictor of thyroid malignancy.

PMID- 18327612
TI  - Seroprevalence and sources of Toxoplasma infection among indigenous and immigrant
      pregnant women in Taiwan.
AB  - Investigation on seroprevalence and risk factors of Toxoplasma gondii infections
      among indigenous and immigrant pregnant women in Mid-Taiwan showed that anti
      Taxoplasma-specific IgG antibody counts were significantly higher in indigenes
      (40.6%) than in immigrants (18.2%), with an odds ratio of OR=3.34 (95% CI: 1.93
      4.80). The titre of Taxoplasma-specific IgG was also significantly higher in
      indigenes than in immigrants (P<0.001). Differences of living styles for
      Toxoplasma infection between the two groups were drinking untreated water
      (OR=2.34, 95% CI: 1.36-4.02), consumption of raw/undercooked meats (OR=10.11 95%
      CI: 4.92-20.78), especially raw/undercooked pork (P=0.000), or raw/undercooked
      viscera (OR=9.16, 95% CI: 2.97-27.94), contact with cats (OR=5.69, 95% CI: 2.83
      11.47), or soil (OR=2.55 95% CI: 1.72-3.80). Differences of risk factors for
      Toxoplasma infection in terms of positive IgG in the two groups were consumption
      of raw/undercooked meats (P=0.005) especially raw/undercooked pork (P=0.004), and
      contact with cats (P=0.013) or soil (P=0.028). It is concluded that
      seroprevalence of Toxoplasma infection is higher in indigenous pregnant women and
      related to their living styles. To prevent congenital toxoplasmosis, health
      education seems required.

PMID- 18327613
TI  - Pdr5-mediated multidrug resistance requires the CPY-vacuolar sorting protein
      Vps3: are xenobiotic compounds routed from the vacuole to plasma membrane
      transporters for efflux?
AB  - In Saccharomyces cerevisiae several members of the ATP-binding cassette
      transporter superfamily efflux a broad range of xenobiotic substrates from cells.
      The vacuole also plays a critical role in multidrug resistance. Mutations in
      genes such as VPS3 that are essential for vacuolar acidification and
      carboxypeptidase Y vacuolar protein-sorting are multidrug sensitive. A similar
      phenotype is also observed with deletions of VPS15, VPS34, and VPS38, which
      encode essential members of the carboxypeptidase Y vacuolar protein-sorting
      pathway. Prior to the work described herein, detoxification by transporters and
      the vacuole were presumed to function independently. We demonstrate that this is
      not the case. Significantly, Vps3 has an epistatic relationship with Pdr5, a
      major yeast multidrug transporter. Thus, a double pdr5, vps3 deletion mutant is
      no more multidrug sensitive than its isogenic single-mutant counterparts.
      Subcellular fractionation experiments and analysis of purified plasma membrane
      vesicles indicate, however, that a vps3 mutation does not affect the membrane
      localization or ATPase activity of Pdr5 even though rhodamine 6G efflux is
      reduced significantly. This suggests that Vps3 and probably other members of the
      carboxypeptidase Y vacuolar protein-sorting pathway are required for relaying
      xenobiotic compounds to transporters in the membrane.

PMID- 18327614
TI  - Response of host plants to periodical cicada oviposition damage.
AB  - Insect oviposition on plants is widespread across many systems, but studies on
      the response of host plants to oviposition damage are lacking. Although patterns
      of oviposition vary spatially and temporally, ovipositing insects that exhibit
      outbreak characteristics may have strong effects on host plants during peak
      abundance. Periodical cicadas (Magicicada spp.), in particular, may reduce the
      performance of host plants when they synchronously emerge in massive numbers to
      mate and oviposit on host plants. Here we provide the first experimental
      manipulation of host plant use by periodical cicadas to evaluate the impact of
      cicada oviposition on plant performance across a diversity of host species within
      an ecologically relevant setting. Using a randomized block design, we established
      a plantation of three native and three exotic host plant species common to the
      successional forests in which cicadas occur. During the emergence of Brood X in
      2004, we employed a highly effective cicada exclusion treatment by netting half
      of the host plants within each block. We assessed multiple measures of host plant
      performance, including overall plant growth and the growth and reproduction of
      individual branches, across three growing seasons. Despite our thorough
      assessment of potential host plant responses to oviposition damage, cicada
      oviposition did not generally inhibit host plant performance. Oviposition
      densities on unnetted host plants were comparable to levels documented in other
      studies, reinforcing the ecological relevance of our results, which indicate that
      cicada oviposition damage did not generally reduce the performance of native or
      exotic host plants.

PMID- 18327615
TI  - Developmental instability in a stem-mining sawfly: can fluctuating asymmetry
      detect plant host stress in a model system?
AB  - Fluctuating asymmetry (FA) may be a sensitive indicator of the stress experienced
      by organisms during their development. Its use in this manner is an intuitively
      appealing, frequently proposed, and potentially powerful tool but remains
      controversial partially because its underlying premise rarely has been critically
      tested. Such tests should include direct comparisons among individuals for which
      levels of FA, stress and fitness have been unambiguously quantified. We assessed
      the use of FA as a bioindicator of the stress experienced during egg-to-adult
      development by the stem-mining sawfly, Cephus cinctus Norton. Sawflies were
      reared in a common garden from seven different wheat cultivars, which were
      selected to represent a gradient of stem solidness, a key factor imposing stress
      on sawflies during development. In this model system, stress was quantified by
      the weight of emergent adults. Fitness was quantified by counting the number of
      eggs in dissected females, which emerge with their full lifetime complement. FA
      was measured for wing length, three wing cells, and three wing veins using image
      analyses. The greatest amount of stress was induced by solid-stemmed cultivars
      from which the adults were significantly smaller than those developing in hollow
      stemmed hosts. In turn, adult weight was positively correlated with fitness. The
      net effect was a 25-fold variation in sawfly fitness, which gave a reasonable
      expectation that FA levels would differ across cultivars. However, FA levels of
      all the traits were similar among cultivars and there was no negative
      relationship between FA and fitness. These results: (1) document the failure of
      FA as an indicator of stress in this model system, (2) identify adult weight as a
      satisfactory indicator of plant-induced stress and sawfly fitness, and (3) add to
      the growing body of literature questioning the value of FA as a biomonitor tool
      of developmental stress.

PMID- 18327616
TI  - Relative importance of host plant patch geometry and habitat quality on the
      patterns of occupancy, extinction and density of the monophagous butterfly Iolana
      iolas.
AB  - Habitat fragmentation is a major cause of species rarity and decline because it
      increases local population extinctions and reduces recolonisation rates of
      remnant patches. Although two major patch characteristics (area and connectivity)
      have been used to predict distribution patterns in fragmented landscapes, other
      factors can affect the occurrence of a species as well as the probability of it
      becoming extinct. In this paper, we study the spatial structure and dynamics of
      the butterfly Iolana iolas in a 75-patch network of its host plant (Colutea
      hispanica) to determine the relative importance of patch area, connectivity and
      habitat quality characteristics on occupancy, extinction and density over the
      period 2003-2006. Occupancy in 2003, incidence (proportion of years occupied) and
      probability of extinction were mostly affected by patch area. Smaller patches
      were less likely to be occupied because they had a higher probability of
      extinction, partly due to environmental stochasticity. The density of I. iolas
      was negatively related to patch area in all study years. Only in 2004 was the
      density of I. iolas positively influenced by fruit production per plant. Our
      results suggest that for I. iolas, and probably for other specialist butterflies
      with clearly delimited resource requirements, metapopulation dynamics can be
      satisfactorily predicted using only geometric variables because most habitat
      characteristics are subsumed in patch area. However, this hypothesis should be
      subject to further testing under diverse environmental conditions to evaluate the
      extent of its generalisation.

PMID- 18327617
TI  - Litter pool sizes, decomposition, and nitrogen dynamics in Spartina alterniflora
      invaded and native coastal marshlands of the Yangtze Estuary.
AB  - Past studies have focused primarily on the effects of invasive plants on litter
      decomposition at soil surfaces. In natural ecosystems, however, considerable
      amounts of litter may be at aerial and belowground positions. This study was
      designed to examine the effects of Spartina alterniflora invasion on the pool
      sizes and decomposition of aerial, surficial, and belowground litter in coastal
      marshlands, the Yangtze Estuary, which were originally occupied by two native
      species, Scirpus mariqueter and Phragmites australis. We collected aerial and
      surficial litter of the three species once a month and belowground litter once
      every 2 months. We used the litterbag method to quantify litter decomposition at
      the aerial, surficial and belowground positions for the three species. Yearly
      averaged litter mass in the Spartina stands was 1.99 kg m(-2); this was 250 and
      22.8% higher than that in the Scirpus (0.57 kg m(-2)) and Phragmites (1.62 kg m(
      2)) stands, respectively. The litter in the Spartina stands was primarily
      distributed in the air (45%) and belowground (48%), while Scirpus and Phragmites
      litter was mainly allocated to belowground positions (85 and 59%, respectively).
      The averaged decomposition rates of aerial, surficial, and belowground litter
      were 0.82, 1.83, and 1.27 year(-1) for Spartina, respectively; these were 52, 62
      and 69% of those for Scirpus litter at corresponding positions and 158, 144 and
      78% of those for Phragmites litter, respectively. The differences in
      decomposition rates between Spartina and the two native species were largely due
      to differences in litter quality among the three species, particularly for the
      belowground litter. The absolute amount of nitrogen increased during the
      decomposition of Spartina stem, sheath and root litter, while the amount of
      nitrogen in Scirpus and Phragmites litter declined during decomposition for all
      tissue types. Our results suggest that Spartina invasion altered the carbon and
      nitrogen cycling in the coastal marshlands of China.

PMID- 18327618
TI  - Escaping an evolutionary trap: preference and performance of a native insect on
      an exotic invasive host.
AB  - Exotic plants may act as population sinks or evolutionary traps for native
      herbivores. The native butterfly Pieris oleracea lays eggs on garlic mustard,
      Alliaria petiolata, but larvae develop very poorly on this exotic invasive plant.
      We examined oviposition preference of individual females and larval performance
      of their offspring for individuals from one area where garlic mustard is well
      established and one where it is absent. These data were used to assess whether
      garlic mustard is being incorporated into or excluded from the diet. Females from
      the area without garlic mustard showed a wide range of preference, families had
      low larval survival on garlic mustard, and larval survivorship showed no
      correlation with mothers' preferences. Females from the area with garlic mustard
      preferred it to the native host, and larval survivorship on garlic mustard was
      positively correlated with the mother's preference. Individuals surviving on
      garlic mustard took longer to pupate and weighed >30% less compared to pupae
      reared on normal hosts. Our results suggest that where garlic mustard is well
      established P. oleracea may be adapting to this plant by both improved larval
      performance and increased adult female oviposition preference for it.

PMID- 18327619
TI  - Variation in woody plant delta(13)C along a topoedaphic gradient in a subtropical
      savanna parkland.
AB  - delta(13)C values of C(3) plants are indicators of plant carbon-water relations
      that integrate plant responses to environmental conditions. However, few studies
      have quantified spatial variation in plant delta(13)C at the landscape scale. We
      determined variation in leaf delta(13)C, leaf nitrogen per leaf area (N(area)),
      and specific leaf area (SLA) in April and August 2005 for all individuals of
      three common woody species within a 308 x 12-m belt transect spanning an upland
      lowland topoedaphic gradient in a subtropical savanna in southern Texas. Clay
      content, available soil moisture, and soil total N were all negatively correlated
      with elevation. The delta(13)C values of Prosopis glandulosa (deciduous N(2)
      fixing tree legume), Condalia hookeri (evergreen shrub), and Zanthoxylum fagara
      (evergreen shrub) leaves increased 1-4 per thousand with decreasing elevation,
      with the delta(13)C value of P. glandulosa leaves being 1-3 per thousand higher
      than those of the two shrub species. Contrary to theory and results from previous
      studies, delta(13)C values were highest where soil water was most available,
      suggesting that some other variable was overriding or interacting with water
      availability. Leaf N(area) was positively correlated with leaf delta(13)C of all
      species (p < 0.01) and appeared to exert the strongest control over delta(13)C
      along this topoedaphic gradient. Since leaf N(area) is positively related to
      photosynthetic capacity, plants with high leaf N(area) are likely to have low p
      (I)/p (a) ratios and therefore higher delta(13)C values, assuming stomatal
      conductance is constant. Specific leaf area was not correlated significantly with
      leaf delta(13)C. Following a progressive growing season drought in July/August,
      leaf delta(13)C decreased. The lower delta(13)C in August may reflect the
      accumulation of (13)C-depleted epicuticular leaf wax. We suggest control of leaf
      delta(13)C along this topoedaphic gradient is mediated by leaf N(area) rather
      than by stomatal conductance limitations associated with water availability.

PMID- 18327620
TI  - Mini-open anterior spine surgery for anterior lumbar diseases.
AB  - Minimally invasive surgeries including endoscopic surgery and mini-open surgery
      are current trend of spine surgery, and its main advantages are shorter recovery
      time and cosmetic benefits, etc. However, mini-open surgery is easier and less
      technique demanding than endoscopic surgery. Besides, anterior spinal fusion is
      better than posterior spinal fusion while considering the physiological loading,
      back muscle function, etc. Therefore, we aimed to introduce the modified "mini
      open anterior spine surgery" (MOASS) and to evaluate the feasibility,
      effectiveness and safety in the treatment of various anterior lumbar diseases
      with this technique. A total of 61 consecutive patients (46 female, 15 male; mean
      age 58.2 years) from 1997 to 2004 were included in this study, with an average
      follow-up of 24-52 (mean 43) months. The disease entities included vertebral
      fracture (20), failed back surgery (13), segmental instability or
      spondylolisthesis (10), infection (8), herniated disc (5), undetermined lesion
      for biopsy (4), and hemivertebra (1). Lesions involved 13 cases at T12-L1, 18 at
      L1-L2, 18 at L2-L3, 22 at L3-L4 and 11 at L4-L5 levels. All patients received a
      single stage anterior-only procedure for their anterior lumbar disease. We used
      the subjective clinical results, Oswestry disability index, fusion rate, and
      complications to evaluate our clinical outcome. Most patients (91.8%) were
      subjectively satisfied with the surgery and had good-to-excellent outcomes. Mean
      operation time was 85 (62-124) minutes, and mean blood loss was 136 (minimal-250)
      ml in the past 6 years. Hospital stay ranged from 4-26 (mean 10.6) days. Nearly
      all cases had improved back pain (87%), physical function (90%) and life quality
      (85%). Most cases (95%) achieved solid or probable solid bony fusion. There were
      no major complications. Therefore, MOASS is feasible, effective and safe for
      patients with various anterior lumbar diseases.

PMID- 18327621
TI  - Periplasmic nitrate reductase revisited: a sulfur atom completes the sixth
      coordination of the catalytic molybdenum.
AB  - Nitrate reductase from Desulfovibrio desulfuricans ATCC 27774 (DdNapA) is a
      monomeric protein of 80 kDa harboring a bis(molybdopterin guanine dinucleotide)
      active site and a [4Fe-4S] cluster. Previous electron paramagnetic resonance
      (EPR) studies in both catalytic and inhibiting conditions showed that the
      molybdenum center has high coordination flexibility when reacted with reducing
      agents, substrates or inhibitors. As-prepared DdNapA samples, as well as those
      reacted with substrates and inhibitors, were crystallized and the corresponding
      structures were solved at resolutions ranging from 1.99 to 2.45 A. The good
      quality of the diffraction data allowed us to perform a detailed structural study
      of the active site and, on that basis, the sixth molybdenum ligand, originally
      proposed to be an OH/OH(2) ligand, was assigned as a sulfur atom after refinement
      and analysis of the B factors of all the structures. This unexpected result was
      confirmed by a single-wavelength anomalous diffraction experiment below the iron
      edge (lambda = 1.77 A) of the as-purified enzyme. Furthermore, for six of the
      seven datasets, the S-S distance between the sulfur ligand and the Sgamma atom of
      the molybdenum ligand Cys(A140) was substantially shorter than the van der Waals
      contact distance and varies between 2.2 and 2.85 A, indicating a partial
      disulfide bond. Preliminary EPR studies under catalytic conditions showed an EPR
      signal designated as a turnover signal (g values 1.999, 1.990, 1.982) showing
      hyperfine structure originating from a nucleus of unknown nature.
      Spectropotentiometric studies show that reduced methyl viologen, the electron
      donor used in the catalytic reaction, does not interact directly with the redox
      cofactors. The turnover signal can be obtained only in the presence of the
      reaction substrates. With use of the optimized conditions determined by
      spectropotentiometric titration, the turnover signal was developed with (15)N
      labeled nitrate and in D(2)O-exchanged DdNapA samples. These studies indicate
      that this signal is not associated with a Mo(V)-nitrate adduct and that the
      hyperfine structure originates from two equivalent solvent-exchangeable protons.
      The new coordination sphere of molybdenum proposed on the basis of our studies
      led us to revise the currently accepted reaction mechanism for periplasmic
      nitrate reductases. Proposals for a new mechanism are discussed taking into
      account a molybdenum and ligand-based redox chemistry, rather than the currently
      accepted redox chemistry based solely on the molybdenum atom.

PMID- 18327622
TI  - Euclidean and fractal geometry of microvascular networks in normal and neoplastic
      pituitary tissue.
AB  - In geometrical terms, tumour vascularity is an exemplary anatomical system that
      irregularly fills a three-dimensional Euclidean space. This physical
      characteristic and the highly variable shapes of the vessels lead to considerable
      spatial and temporal heterogeneity in the delivery of oxygen, nutrients and
      drugs, and the removal of metabolites. Although these biological characteristics
      are well known, quantitative analyses of newly formed vessels in two-dimensional
      histological sections still fail to view their architecture as a non-Euclidean
      geometrical entity, thus leading to errors in visual interpretation and
      discordant results from different laboratories concerning the same tumour. We
      here review the literature concerning microvessel density estimates (a Euclidean
      based approach quantifying vascularity in normal and neoplastic pituitary
      tissues) and compare the results. We also discuss the limitations of Euclidean
      quantitative analyses of vascularity and the helpfulness of a fractal geometry
      based approach as a better means of quantifying normal and neoplastic pituitary
      microvasculature.

PMID- 18327623
TI  - Disentangling perceptual and motor components in inhibition of return.
AB  - Following an abrupt onset of a peripheral stimulus (a cue), the response to a
      visual target is faster when the target appears at the cued position than when it
      appears at other positions. However, if the stimulus onset asynchrony (SOA) is
      longer than approximately 300 ms, the response to the target is slower at the
      cued position than that at other positions. This phenomenon of a longer response
      time to cued targets is called "inhibition of return" (IOR). Previous hypotheses
      propose contributions of both response inhibition and attentional inhibition at
      cued position to IOR, and suggest that responding to the cue can eliminate the
      component of response inhibition. The current study uses tasks either executing
      or withholding response to the cue to investigate the relative contributions of
      response and attention components to IOR. A condition with bilateral display of
      the cue is also chosen as a control condition, and eight different SOAs between
      1,000 and 2,750 ms are tested. Compared to the control condition, response delay
      to the target at a cued position is eliminated by responding to the cue, and a
      response advantage to the target at an uncued position is not affected by
      responding to the cue. Furthermore, both response delay at a cued position and
      response advantage at an uncued position decrease with SOA in the time window
      tested in these experiments. The results reported here indicate a dominant
      response inhibition at a cued position and a primary attentional allocation at an
      uncued position for IOR. Nonsignificant perceptual/attentional suppression at a
      cued position is argued to be a benefit for visual detection in a changing world.

PMID- 18327624
TI  - Cardiologist's knowledge and attitudes about obstructive sleep apnea: a survey
      study.
AB  - Obstructive sleep apnea (OSA) is associated with cardiovascular diseases, yet
      available data suggests cardiologists underreport OSA. This study assessed
      whether cardiologists' knowledge and attitudes about OSA contribute to this
      finding. A previously validated questionnaire, the "Obstructive Sleep Apnea
      Knowledge and Attitudes Questionnaire" (OSAKA), was modified by the addition of
      20 knowledge items and one attitude question to include a total of 38 knowledge
      items and six attitude questions. The questionnaire was mailed to a random
      sampling of 420 cardiologists in the USA. Ninety-two cardiologists (22%) returned
      completed questionnaires. Mean age was 48 +/- 10 years, 74% were male, and 52%
      were general cardiologists. Mean score on the original OSAKA portion of the
      questionnaire (76%) was similar to previously reported scores of primary care
      physicians (PCPs), while the total knowledge score was 77%. Scores did not differ
      by gender (p = 0.7) or subspecialty (p = 0.3), and there were no correlations
      between knowledge and age or years in practice. While 80% stated that identifying
      patients at risk for OSA was very or extremely important, only 68% felt confident
      identifying these patients, and only 18% felt confident managing OSA patients.
      There was no difference in mean total attitude score when analyzed by age,
      gender, years of practice, and subspecialty. Total knowledge scores correlated
      with attitude scores (r = 0.29, p = 0.004). Cardiologists' knowledge about OSA is
      comparable to that of PCPs. Cardiologists may lack confidence identifying and
      managing patients with OSA, factors that may contribute to their low rate of
      reporting OSA.

PMID- 18327625
TI  - Surgical outcomes of laparoscopic cholecystectomy for severe acute cholecystitis.
AB  - The aim of this study was to evaluate the surgical outcomes of laparoscopic
      cholecystectomy (LC) in patients who were diagnosed with severe acute
      cholecystitis (SAC) and to clarify the useful treatment modalities of SAC. Of 112
      patients who presented SAC, we selected 99 patients and divided them into 3
      groups: 37 patients who underwent preoperative percutaneous transhepatic
      gallbladder drainage (PTGBD; group 1), 62 patients with SAC but not indicated for
      PTGBD (group 2), and 59 patients with acute and chronic cholecystitis (group 3).
      The conversion rate was 2.7% (1/37) in group 1, 6.5% (4/62) in group 2, and 1.7%
      (1/59) in group 3. In groups 1 and 2, the postoperative stay and operative time
      were longer than those in group 3 with significant difference, respectively
      (P<0.05). In group 2, there was correlation not only between postoperative stay
      and age but also between postoperative stay and ASA class (P<0.05). In group 2,
      there was no correlation between time to operation and operative time and also
      between time to operation and postoperative stay, however, there was surprisingly
      significant correlation between time to operation and conversion rate in SAC
      (P=0.018). In conclusion, PTGBD should selectively be performed in patients with
      severe comorbidities rather than improving surgical outcomes of LC for severe
      acute cholecystitis. If patients are not indicated for PTGBD, an early
      laparoscopic cholecystectomy is recommended because it can decrease conversion
      rate, although it cannot decrease operative time and postoperative stay.

PMID- 18327626
TI  - Bowel habits after bariatric surgery.
AB  - BACKGROUND: Disordered bowel habits might influence quality of life after
      bariatric surgery. Different types of bariatric operations-gastric banding (AGB),
      Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD)-might alter
      bowel habits as a consequence of the surgical procedure used. Whether change in
      bowel habits affects quality of life after AGB, RYGB, or BPD differently is
      unknown. METHODS: The study group contained 290 severely obese patients
      undergoing bariatric surgery between August 1996 and September 2004 [BPD: n =
      103, 64.1% women, age 43 +/- 1 years (mean +/- SEM), BMI 53.9 +/- 0.9 kg/m(2),
      weight 153.4 +/- 2.9 kg; Roux-en-Y gastric bypass: n = 126, 73.0% women, age 43
      +/- 1 years, BMI 44.2 +/- 0.3 kg/m(2), weight 123.8 +/- 1.5 kg; adjustable
      gastric banding (AGB): n = 61, 57.4% women, age 44 +/- 1 years, BMI 49.9 +/- 0.5
      kg/m(2), weight 146.1 +/- 2.0 kg). Changes in bowel habits, flatulence, flatus
      odor, and effects on social life were estimated at least 4 months after surgery
      using a self-administered questionnaire. RESULTS: Fecal consistency changed
      significantly after surgery. Loose stools and diarrhea were more frequent after
      BPD and RYGB (P < 0.001) but more so after BPD than after either RYGB or AGB (P <
      0.002). Constipation was more likely after AGB (P = 0.03). In addition,
      malodorous flatus affecting social life was more frequent after BPD than after
      either RYGB or AGB (P < 0.003). Furthermore, flatus frequency increased after BPD
      and RYGB, and patients were more bothered by their malodorous flatus than after
      AGB (all P < 0.001). Flatus severity score was highest in BPD, intermediate in
      RYGB, and lowest in AGB patients (all P < 0.001), a difference that was not
      influenced by frequency of metabolic syndrome before and after surgery. Moreover,
      observation period after surgery had no influence on overall results of bowel
      habits. Subsore quality of life bariatric analysis and reporting outcome system
      (BAROS) scores were largely similar between all three groups. However, flatulence
      severity score correlated inversely with quality of life estimated by BAROS in
      BPD and RYGB, but not in AGB patients. CONCLUSIONS: The type of bariatric surgery
      affects bowel habits in an operation-specific manner, resulting mainly in
      diarrhea after BPD and RYGB, and constipation after AGB. Flatulence severity
      impairs quality of life most in BPD, is intermediate in RYGB, and is only minor
      after AGB, a phenomenon that was only partially mirrored in quality-of-life
      measures of BAROS.

PMID- 18327627
TI  - THA using an anatomic stem in patients with femoral head osteonecrosis.
AB  - Treating young patients with femoral head osteonecrosis (ON) remains challenging.
      Anatomic stems were introduced in the 1980s and 1990s to improve the proximal
      canal fit in an attempt to enhance long-term implant survival, an important
      aspect of treating young patients. We began using one design in 1993 and asked
      three questions to confirm whether the design criteria improved outcomes in
      patients with ON: (1) What is the long term survivorship of these implants?; (2)
      What is the amount and rate of wear?; and (3) What is the incidence of
      osteolysis? We retrospectively reviewed 56 patients (69 hips) who underwent THA
      for femoral head ON with a cementless anatomic stem proximally coated with
      hydroxyapatite. Four patients (four hips) were lost to followup and 16 patients
      (19 hips) died. In the remaining 36 patients (46 hips) the minimum followup was
      10 years (mean, 11.2 years; range, 10-13 years). The mean age at operation was
      48.6 years. The average Harris hip score at last followup was 87 points. Worst
      case survivorship was 58.1% at 13 years and best-case was 93.3%. The average
      linear wear of the polyethylene liner was 2.02 mm and the average annual wear was
      0.18 mm per year. Thirty-seven hips (80%) had femoral osteolysis and 14 (30%) had
      acetabular osteolysis. One patient who had extensive femoral osteolysis and stem
      loosening was revised at 11.2 years postoperatively. The high rates of
      polyethylene wear and osteolysis are of concern.

PMID- 18327628
TI  - Increased oxacillin resistance in thigh pyomyositis in diabetic patients.
AB  - Thigh abscesses due to pyomyositis are uncommon. To guide empiric antibiotic
      therapy in diabetics we determined the rate of such infections due to oxacillin
      resistant Staphylococcus aureus and Gram-negative organism infections, and
      whether the occurrence of oxacillin-resistant pathogens increased during the
      study period. We retrospectively reviewed 39 adult patients with diabetes
      mellitus treated for a deep thigh abscess. There were 29 men and 10 women; their
      mean age was 45 years. Comorbidities were present in 15 patients. S. aureus was
      the most common pathogen, present in 82% (32/39) of our patients. Gram-negative
      organisms were cultured in 14% (6/39) of patients and anaerobes in 10% (4/39).
      The infection was polymicrobial in 12 of 39 patients (31%). Oxacillin-resistant
      S. aureus comprised 25% (8/32) of infections due to S. aureus. Oxacillin
      resistance increased during the last 3 years of this study from one of 18 S.
      aureus isolates from 1994 to 2004 to seven of 14 isolates from 2004 to 2006. In
      diabetic patients with thigh pyomyositis, empiric antibiotic therapy should
      provide broad spectrum coverage for oxacillin-resistant S. aureus, Gram-negative,
      as well as anaerobic organisms. LEVEL OF EVIDENCE: Level IV, diagnostic study.
      See the Guidelines for Authors for a complete description of levels of evidence.

PMID- 18327629
TI  - Transtrochanteric posterior rotational osteotomy for osteonecrosis.
AB  - When osteonecrosis is located in the mid- to posterior region, we generally
      perform a transtrochanteric posterior rotational osteotomy. We retrospectively
      reviewed the clinical and radiographic results in 47 consecutive patients (51
      hips) in whom we performed posterior rotational osteotomies. The average age was
      37 years at the time of surgery. There were 30 male and 17 female patients.
      Thirty-six hips were ARCO Stage III, and 15 were Stage IV. Conversion to THA was
      defined as the failure end point. Three patients died and one was lost to
      followup. We were therefore able to follow 43 patients (46 of the 51 hips, or
      90%) a minimum of 1.2 years (average, 12 years; range, 1.2-21 years). We used the
      Harris hip score for preoperative and most recent followup. The average
      preoperative Harris hip score of 52 points improved to an average of 84 at the
      latest followup. Radiographically, the osteonecrosis in 30 hips (65%) had no
      progressive collapse, and 13 (28%) showed osteoarthritic changes, but no patients
      underwent THA. A posterior rotational osteotomy appears useful for patients with
      extensive necrosis and advanced collapse.

PMID- 18327630
TI  - Untreated asymptomatic hips in patients with osteonecrosis of the femoral head.
AB  - Because there is no consensus regarding the factors predicting femoral head
      collapse in asymptomatic osteonecrosis of the hip, we studied the risk factors
      for collapse. Between 1990 and 2000, we used MRI to confirm asymptomatic
      osteonecrosis of the femoral head in 81 patients (81 hips) whose other hip had
      nontraumatic symptomatic osteonecrosis and we monitored them prospectively. The
      minimum followup was 5 years (mean, 8.3 years; range, 5-16 years). At the latest
      followup, 31 hips (38%) were symptomatic and 26 hips (32%) had collapsed. The
      mean interval between diagnosis and collapse was 4.1 years. We observed no
      correlation between femoral head collapse and patients' age, gender, weight,
      presumed cause of osteonecrosis, or length of followup. With combined factors,
      only extent of large necrotic lesion (hazard ratio, 4.06; 95% confidence
      interval, 1.29-12.77) and location of Type C2 necrotic lesion (hazard ratio,
      6.35; 95% confidence interval, 1.18-34.11) predicted collapse.

PMID- 18327631
TI  - Comparison of taurine biosynthesis ability between juveniles of Japanese flounder
      and common carp.
AB  - This study was conducted to investigate taurine deficiency and the ability of
      taurine biosynthesis in both juvenile Japanese flounder (JF) and juvenile common
      carp (CC) in vivo using low taurine level diets. Three different taurine level
      diets were prepared by the supplementation of taurine to the basal composition
      (JF--0, 0.5 and 1.5% in JF; CC--0, 1, 3% in CC). The final average body weight
      and feed efficiency of JF fed the JF - 1.5% was significantly higher than those
      of fish fed on the JF--0%. On the other hand, no significant difference was
      observed in CC fed with CC--0, 1, and 3% diets. The taurine retention rate was
      negative in the case of JF-fed with the taurine-free supplement (JF--0%). On the
      other hand, the taurine retention rate was about 280% in the case of CC-fed with
      the taurine-free supplement (CC--0%). These findings indicate that while taurine
      is essential for growth of JF, it is not essential for the growth of CC.

PMID- 18327632
TI  - Up-regulation of rat adipose tissue adiponectin gene expression by long-term but
      not by short-term food restriction.
AB  - Beneficial effects of food restriction as well as elevated circulating
      adiponectin concentration on the cardiovascular system, lipid metabolism and non
      insulin dependent diabetes have been reported. The present article indicates that
      the reduction in rat body and adipose tissue weight after long-term (1 month)
      food restriction (either 75% or 50% of ad libitum food intake) was accompanied by
      the increase in serum adiponectin concentration. The increase in serum
      adiponectin concentration is the result of the significant increase in white
      adipose tissue adiponectin gene expression. In contrast to long-term food
      restriction, short-term (3 days) food restriction (either 75% or 50% of ad
      libitum food intake) did not influence body and fat mass as well as serum
      adiponectin concentration and white adipose tissue adiponectin mRNA level. The
      obtained results suggest that long-term food restriction is necessary to increase
      in serum adiponectin concentration that could be beneficial, to prevent some
      disorders associated with low serum adiponectin concentration like obesity and
      obesity-related diseases.

PMID- 18327633
TI  - SOGS and CGPI: parallel comparison on a diverse population.
AB  - The Northern Territory of Australia, one of the most demographically and socially
      diverse jurisdictions in the country, conducted its first population-based
      gambling and problem gambling prevalence survey in 2005. Both the South Oaks
      Gambling Screen (SOGS) and the Canadian Problem Gambling Index (CPGI) were
      administered to the same sample of respondents. Using data from this survey, the
      current paper presents a parallel comparison of the respective screens with
      particular reference to gender, region, and the socio-demographic characteristics
      of respondents. The respective screens produced significantly different groups of
      problem gamblers as measured by their association with a range of socio
      demographic variables. Specifically, the large number of SOGS items related to
      money issues may cause selective overrepresentation among low socioeconomic
      groups, including Indigenous people, who exist in relatively high proportions in
      the Northern Territory. In addition, there existed substantial gender-based
      differences within screens. Identified female problem gamblers were associated
      with household level variables (i.e. employment status, household type and
      marital status), while males were associated with socio-economic variables
      including language, education, and income. Further research is required to
      validate the use of problem gambling screens within the Indigenous population and
      to understand the role of gender in the experience and categorisation of problem
      gambling.

PMID- 18327635
TI  - How to test the extreme male brain theory of autism in terms of foetal androgens?

PMID- 18327636
TI  - Examining the validity of autism spectrum disorder subtypes.
AB  - The classification of autism spectrum disorders (ASDs) is a topic of debate among
      clinicians and researchers with many questioning the validity of the distinction
      among subtypes. This manuscript examines the validity of three ASD subtypes
      (Autism, Asperger's, and PDDNOS) by reviewing 22 studies published between 1994
      and 2006. We reviewed studies that examined differences between the subtypes in
      terms of clinical and demographic characteristics, neuropsychological profiles,
      comorbidity, and prognosis. Results largely did not support differences between
      autism and Asperger's disorder based on current diagnostic criteria. Overall, the
      most salient group differences were noted when samples were categorized on IQ.
      Drawing definitive conclusions is difficult due to the inconsistent application
      of diagnostic criteria and circularity in methods.

PMID- 18327637
TI  - Patho-biological aspects of basal-like breast cancer.
AB  - Breast cancer comprises a remarkably diverse group of diseases in terms of
      presentation, morphology, molecular profile and response to therapy. Recent gene
      expression profiling of breast cancer has identified specific molecular subtypes
      of clinical significance. Basal-like cancers (BLC) comprise a group of tumours
      that are characterised by an expression signature similar to that of the
      basal/myoepithelial cells of the breast and cluster together with BRCA1
      associated tumours. Although BLC has fascinated oncologists and scientists alike
      due to its enigmatic clinical and pathological parameters, there is no consensus
      about the definition and method of identification in routine practice of this
      rather heterogeneous group of cancers. Furthermore, the prognostic significance
      of BLCs and response to specific chemotherapy regimens are still a matter debate.
      In this review, we discuss the molecular and morphological features, prognostic
      significance of BLC, and explore its impact on the concept of the breast cancer
      stem cell.

PMID- 18327638
TI  - HER2 status predicts the presence of circulating tumor cells in patients with
      operable breast cancer.
AB  - INTRODUCTION: Circulating tumor cells (CTCs) correlate with worse prognosis in
      patients with metastatic breast cancer, but there are little data on CTCs in
      operable patients. We hypothesized that primary tumor characteristics would
      predict the likelihood of identifying CTCs in patients with operable breast
      cancer. METHODS: Clinical and pathological data from 92 patients with operable
      breast cancer were collected. The CellSearch system was used to detect CTCs in 30
      ml of peripheral blood. CTCs were defined as nucleated cells lacking CD45 but
      expressing cytokeratins 8, 18, or 19. Univariate analysis was performed to
      determine if the presence of any primary tumor characteristic was predictive of
      CTCs. As a secondary objective we evaluated if nodal or bone marrow status was
      predictive of CTCs. RESULTS: Thirty-eight percent of patients (35/92) had
      evidence of CTCs, with a median number of 1.0 CTC per CTC positive patient (range
      1-22). HER2 status was the sole primary tumor characteristic that reliably
      predicted the presence of CTCs (P = 0.01, risk ratio = 3.66). No significant
      association was found between the presence of CTCs and tumor size (T), estrogen
      receptor (ER) status, progesterone receptor (PR) status, grade, histologic type,
      degree of nodal involvement (N), lymphovascular invasion (LVI) or Ki-67
      proliferation. Bone marrow micrometastases were found in 17/64 (26.6%) of the
      patients but did not correlate with the presence of CTCs. CONCLUSION: HER2 status
      was the only primary tumor characteristic that correlated with the presence of
      CTCs. Long-term follow-up will be required to determine the significance of CTCs
      in operable breast cancer.

PMID- 18327639
TI  - Novel sugar-cholestanols as anticancer agents against peritoneal dissemination of
      tumor cells.
AB  - Chemically synthesized sugar-cholestanols with mono-, di-, and tri-saccharides
      attached to cholestanol showed strong inhibiting activity against the
      proliferation of colorectal and gastric cancer cells. In contrast, cholestanol
      without sugar moieties was totally ineffective. Furthermore, when cancer cells
      were exposed to GlcNAcRbetacholestanol (R=(-) or beta1-3Gal), the compound was
      rapidly taken up via the lipid rafts/microdomains on the cell surface. The uptake
      of sugar-cholestanol in mitochondria increased gradually and was followed by the
      release of cytochrome c from mitochondria and the activation of apoptotic signals
      through the mitochondrial pathway and the caspase cascade, leading to apoptotic
      cell death, characterized by DNA ladder formation and nuclear fragmentation.
      Additionally, the examination of GlcNAcRbetacholestanol in a mouse model of
      peritoneal dissemination showed a dramatic reduction of tumor growth (P < 0.003)
      and prolonged mouse survival time (P<0.0001). Based on these observations, we
      believe that the sugar-cholestanols described here have clinical potential as
      novel anticancer agents.

PMID- 18327640
TI  - Both atomoxetine and stimulants improve quality of life in an ADHD population
      treated in a community clinic.
AB  - OBJECTIVE: To evaluate change in quality of life in a community clinic ADHD
      population treated with atomoxetine or stimulants. No direct comparisons between
      atomoxetine and stimulants to improve quality of life in ADHD are available.
      METHODS: A prospective, nonrandomized comparison between ADHD patients treated
      with atomoxetine or stimulants in one clinic. Structured diagnostic assessment
      tools and a specific quality of life measure were used. RESULTS: 84 patients
      (atomoxetine n = 39/stimulants n = 45), between the ages of 5 and 18, were
      treated for approximately 8 months. At end point, there were no significant
      differences in improvements of quality of life between the two groups. Age,
      participation in psychotherapy, and parental disability were not correlated with
      quality of life changes. Patients with lower baseline scores improved most.
      CONCLUSIONS: Both atomoxetine and stimulants led to a modest increase in quality
      of life in this community clinic ADHD population.

PMID- 18327641
TI  - Synthetic microvascular networks for quantitative analysis of particle adhesion.
AB  - We have developed a methodology to study particle adhesion in the microvascular
      environment using microfluidic, image-derived microvascular networks on a chip
      accompanied by Computational Fluid Dynamics (CFD) analysis of fluid flow and
      particle adhesion. Microfluidic networks, obtained from digitization of in vivo
      microvascular topology were prototyped using soft-lithography techniques to
      obtain semicircular cross sectional microvascular networks in
      polydimethylsiloxane (PDMS). Dye perfusion studies indicated the presence of well
      perfused as well as stagnant regions in a given network. Furthermore,
      microparticle adhesion to antibody coated networks was found to be spatially non
      uniform as well. These findings were broadly corroborated in the CFD analyses.
      Detailed information on shear rates and particle fluxes in the entire network,
      obtained from the CFD models, were used to show global adhesion trends to be
      qualitatively consistent with current knowledge obtained using flow chambers.
      However, in comparison with a flow chamber, this method represents and
      incorporates elements of size and complex morphology of the microvasculature.
      Particle adhesion was found to be significantly localized near the bifurcations
      in comparison with the straight sections over the entire network, an effect not
      observable with flow chambers. In addition, the microvascular network chips are
      resource effective by providing data on particle adhesion over physiologically
      relevant shear range from even a single experiment. The microfluidic
      microvascular networks developed in this study can be readily used to gain
      fundamental insights into the processes leading to particle adhesion in the
      microvasculature.

PMID- 18327642
TI  - Defining "prodromal" Alzheimer's disease, frontotemporal dementia, and Lewy body
      dementia: are we there yet?

PMID- 18327643
TI  - Review of physiology, clinical manifestations, and management of hypothalamic
      obesity in humans.
AB  - Hypothalamic injury from acquired structural damage due to infiltrative disease,
      tumor, or their treatment aftereffects frequently results in the development of
      an obesity syndrome characterized by a rapid, unrelenting weight gain that may be
      accompanied by severe hyperphagia. Weight gain occurs from the disruption of the
      normal homeostatic functioning of the hypothalamic centers responsible for
      controlling satiety and hunger and regulating energy balance with resulting
      hyperphagia, autonomic imbalance, reduction of energy expenditure, and
      hyperinsulinemia. Curtailment of weight increase has traditionally been
      refractory to usual dietary and lifestyle interventions. Pharmacotherapy
      targeting insulin secretion and augmenting sympathetic output have been attempted
      to promote weight loss or attenuate weight gain. In addition, case reports
      suggest that bariatric surgery may be an effective treatment option for these
      patients. Hormonal deficits are often present, and their management may also have
      consequences for weight control. Hypothalamic obesity confers significant
      morbidity and mortality, and there is a need for greater elucidation of its risk
      factors and pathogenesis so that more effective interventions can be developed.

PMID- 18327644
TI  - Helitron mediated amplification of cytochrome P450 monooxygenase gene in maize.
AB  - The mass movement of gene sequences by Helitrons has significantly contributed to
      the lack of gene collinearity reported between different maize inbred lines.
      However, Helitron captured-genes reported to date represent truncated versions of
      their progenitor genes. In this report, we provide evidence that maize CYP72A27
      Zm gene represents a cytochrome P450 monooxygenase (P450) gene recently captured
      by a Helitron and transposed into an Opie-2 retroposon. The four exons of the
      CYP72A27 gene contained within the element contain a putative open reading frame
      (ORF) for 428 amino acid residues. We provide evidence that Helitron captured
      CYP72A27-Zm is transcribed. To identify the progenitor gene and the evolutionary
      time of capture, we searched the plant genome database and discovered other
      closely related CYP72A27-Zm genes in maize and grasses. Our analysis indicates
      that CYP72A27-Zm represents an almost complete copy of maize CYP72A26-Zm gene
      captured by a Helitron about 3.1 million years ago (mya). The Helitron-captured
      gene then duplicated twice, approximately 1.5-1.6 mya giving rise to CYP72A36-Zm
      and CYP72A37-Zm. These data provide evidence that Helitrons can capture and
      mobilize intact genes that are transcribed and potentially encode biologically
      relevant proteins.

PMID- 18327645
TI  - Molecular evolution of paclitaxel biosynthetic genes TS and DBAT of Taxus
      species.
AB  - Evolutionary patterns of sequence divergence were analyzed in genes from the
      conifer genus Taxus (yew), encoding paclitaxel biosynthetic enzymes taxadiene
      synthase (TS) and 10-deacetylbaccatin III-10 beta-O-acetyltransferase (DBAT). N
      terminal fragments of TS, full-length DBAT and internal transcribed spacer (ITS)
      were amplified from 15 closely related Taxus species and sequenced. Premature
      stop codons were not found in TS and DBAT sequences. Codon usage bias was not
      found, suggesting that synonymous mutations are selectively neutral. TS and DBAT
      gene trees are not consistent with the ITS tree, where species formed
      monophyletic clades. In fact, for both genes, alleles were sometimes shared
      across species and parallel amino acid substitutions were identified. While both
      TS and DBAT are, overall, under purifying selection, we identified a number of
      amino acids of TS under positive selection based on inference using maximum
      likelihood models. Positively selected amino acids in the N-terminal region of TS
      suggest that this region might be more important for enzyme function than
      previously thought. Moreover, we identify lineages with significantly elevated
      rates of amino acid substitution using a genetic algorithm. These findings
      demonstrate that the pattern of adaptive paclitaxel biosynthetic enzyme evolution
      can be documented between closely related Taxus species, where species-specific
      taxane metabolism has evolved recently.

PMID- 18327646
TI  - Good genes, complementary genes and human mate preferences.
AB  - The past decade has witnessed a rapidly growing interest in the biological basis
      of human mate choice. Here we review recent studies that demonstrate preferences
      for traits which might reveal genetic quality to prospective mates, with
      potential but still largely unknown influence on offspring fitness. These include
      studies assessing visual, olfactory and auditory preferences for potential good
      gene indicator traits, such as dominance or bilateral symmetry. Individual
      differences in these robust preferences mainly arise through within and between
      individual variation in condition and reproductive status. Another set of studies
      have revealed preferences for traits indicating complementary genes, focussing on
      discrimination of dissimilarity at genes in the major histocompatibility complex
      (MHC). As in animal studies, we are only just beginning to understand how
      preferences for specific traits vary and inter-relate, how consideration of good
      and compatible genes can lead to substantial variability in individual mate
      choice decisions and how preferences expressed in one sensory modality may
      reflect those in another. Humans may be an ideal model species in which to
      explore these interesting complexities.

PMID- 18327647
TI  - Selfish genetic elements and sexual selection: their impact on male fertility.
AB  - Females of many species mate with more than one male (polyandry), yet the
      adaptive significance of polyandry is poorly understood. One hypothesis to
      explain the widespread occurrence of multiple mating is that it may allow females
      to utilize post-copulatory mechanisms to reduce the risk of fertilizing their
      eggs with sperm from incompatible males. Selfish genetic elements (SGEs) are
      ubiquitous in eukaryotes, frequent sources of reproductive incompatibilities, and
      associated with fitness costs. However, their impact on sexual selection is
      largely unexplored. In this review we examine the link between SGEs, male
      fertility and sperm competitive ability. We show there is widespread evidence
      that SGEs are associated with reduced fertility in both animals and plants, and
      present some recent data showing that males carrying SGEs have reduced paternity
      in sperm competition. We also discuss possible reasons why male gametes are
      particularly vulnerable to the selfish actions of SGEs. The widespread reduction
      in male fertility caused by SGEs implies polyandry may be a successful female
      strategy to bias paternity against SGE-carrying males.

PMID- 18327648
TI  - 'Good-genes' and 'compatible-genes' effects in an Alpine whitefish and the
      information content of breeding tubercles over the course of the spawning season.
AB  - Some models of sexual selection predict that individuals vary in their genetic
      quality and reveal some of this variation in their secondary sexual
      characteristics. Alpine whitefish (Coregonus sp.) develop breeding tubercles
      shortly before their spawning season. These tubercles are epidermal structures
      that are distributed regularly along the body sides of both males and females.
      There is still much unexplained variation in the size of breeding tubercles
      within both sexes and with much overlap between the sexes. It has been suggested
      that breeding tubercles function to maintain body contact between the mating
      partners during spawning, act as weapons for defence of spawning territories, or
      are sexual signals that reveal aspects of genetic quality. We took two samples of
      whitefish from their spawning place, one at the beginning and one around the peak
      of spawning season. We found that females have on average smaller breeding
      tubercles than males, and that tubercle size partly reveals the stage of gonad
      maturation. Two independent full-factorial breeding experiments revealed that
      embryo mortality was significantly influenced by male and female effects. This
      finding demonstrates that the males differed in their genetic quality (because
      offspring get nothing but genes from their fathers). Tubercle size was negatively
      linked to some aspects of embryo mortality in the first breeding experiment but
      not significantly so in the second. This lack of consistency adds to inconsistent
      results that were reported before and suggests that (i) some aspects of genetic
      quality are not revealed in breeding tubercles while others are, or (ii)
      individuals vary in their signaling strategies and the information content of
      breeding tubercles is not always reliable. Moreover, the fact that female
      whitefish have breeding tubercles of significant size while males seem to have
      few reasons to be choosy suggests that the tubercles might also serve some
      functions that are not linked to sexual signaling.

PMID- 18327649
TI  - Sexual selection in the cricket Gryllus bimaculatus: no good genes?
AB  - Recent studies have suggested that females of the field cricket Gryllus
      bimaculatus exercise post-copulatory choice over the paternity of their
      offspring. There is evidence that these choices are made in relation to the
      genetic compatibility of mates rather than their absolute quality, but the
      magnitude of heritable differences in males has not been thoroughly examined.
      Using a half-sib breeding design we measured additive genetic variance and dam
      effects in a suite of reproductive and non-reproductive traits. Both components
      explained relatively little of the phenotypic variance across traits. The dam
      component in our design contains variance caused by both maternal effects and
      dominance. If maternal effects are negligible as suggested by previous studies,
      our data suggest that dominance variance is an important source of variation in
      these traits. The lack of additive genetic variation, but possible existence of
      large amounts of non-additive genetic variation is consistent with the idea that
      female mate choice and multiple mating may be driven by differences in genetic
      compatibility between potential mates rather than by differences in genetic
      quality.

PMID- 18327650
TI  - Condition-dependence, genotype-by-environment interactions and the lek paradox.
AB  - The lek paradox states that maintaining genetic variation necessary for 'indirect
      benefit' models of female choice is difficult, and two interrelated solutions
      have been proposed. 'Genic capture' assumes condition-dependence of sexual
      traits, while genotype-by-environment interactions (GEIs) offer an additional way
      to maintain diversity. However, condition-dependence, particularly with GEIs,
      implies that environmental variation can blur the relationship between male
      displays and offspring fitness. These issues have been treated separately in the
      past. Here we combine them in a population genetic model, and show that
      predictions change not only in magnitude but also in direction when the timing of
      dispersal between environments relative to the life cycle is changed. GEIs can
      dramatically improve the evolution of costly female preferences, but also hamper
      it if much dispersal occurs between the life history stage where condition is
      determined and mating. This situation also arises if selection or mutation rates
      are too high. In general, our results highlight that when evaluating any
      mechanism promoted as a potential resolution of the lek paradox, it is not
      sufficient to focus on its effects on genetic variation. It also has to be
      assessed to what extent the proposed mechanism blurs the association between male
      attractiveness and offspring fitness; the net balance of these two effects can be
      positive or negative, and often strongly context-dependent.

PMID- 18327651
TI  - Intestinal adenomagenesis involves core molecular signatures of the epithelial
      mesenchymal transition.
AB  - The epithelial-mesenchymal transition (EMT) occurs commonly during carcinoma
      invasion and metastasis, but not during early tumorigenesis. Microarray data
      demonstrated elevation of vimentin, a mesenchymal marker, in intestinal adenomas
      from Apc Min/+ (Min) mice. We have tested the involvement of EMT in early
      tumorigenesis in mammalian intestines by following EMT-associated markers.
      Elevated vimentin RNA expression and protein production were detected within
      neoplastic cells in murine intestinal adenomas. Similarly, vimentin protein was
      detected in both adenomas and invasive adenocarcinomas of the human colon, but
      not in the normal colonic epithelium or in hyperplastic polyps. Expression of E
      cadherin varied inversely with vimentin. In addition, the expression of
      fibronectin was elevated while that of E-cadherin decreased. Canonical E-cadherin
      suppressors, such as Snail, were not elevated in the same tumor. Elevated
      vimentin expression in the adenoma was not correlated with persistent Ras
      signaling, but was strongly correlated with reduced proliferation indices, active
      Wnt signaling, and TGF-beta signaling, as demonstrated by its dependence on
      Smad3. We designate our observations of expression of only some of the canonical
      features of EMT as "truncated EMT". These unexpected observations are interpreted
      as reflecting the involvement of a core of the EMT system during the tissue
      remodeling of early tumorigenesis.

PMID- 18327652
TI  - Divergent mechanisms in generating molecular variations of alphaRYR and betaRYR
      in turkey skeletal muscle.
AB  - (1) Molecular variations in two turkey skeletal muscle ryanodine receptor gene
      isoforms, alphaRYR and betaRYR, were analyzed by cloning and sequencing the
      entire cDNAs of the two isoforms. (2) Ten alternative splicing transcript
      variants (ASTVs) in the alphaRYR isoform were identified. These variants were
      clustered in three alternative splicing regions (ASRs). Two ASRs overlap with the
      divergent regions (DRs) of the two isoforms. Only four ASTVs did not contain a
      frame shift and potentially can be translated into alphaRYR channel proteins. The
      expression of these three ASTVs was developmentally or environmentally regulated.
      (3) Ten SNPs and eight haplotypes, divergent in the ten SNP positions, were
      identified in betaRYR. Although the ten SNPs were synonymous, different mRNA
      secondary structures of betaRYR and different stability of the structures were
      predicted for several SNPs. (4) The intriguing finding of this study is that
      alphaRYR and betaRYR use completely divergent mechanisms to generate molecular
      variations. Alternative splicing generates ASTVs of alphaRYR, whereas the
      presence of SNPs may change the secondary mRNA structure of betaRYR. These
      divergent mechanisms could affect calcium channel activity of either or both RYR
      isoforms.

PMID- 18327653
TI  - Mycorrhizal colonisation of mountain birch (Betula pubescens ssp. czerepanovii)
      along three environmental gradients: does life in harsh environments alter plant
      fungal relationships?
AB  - Environmental stress affects ectomycorrhizal communities (ECM), but it is not
      known how general the detected ECM responses are. We investigated ECM fungi on
      roots of mountain birch, Betula pubescens subsp. czerepanovii (Orlova) Hamet
      Ahti, along three environmental gradients, two natural (altitude, seashore) and
      one human-induced (pollution), within the Kola Peninsula, NW Russia. Chlorophyll
      fluorescence of birch leaves indicated no environmental stress even in the
      conditions that were presumed most stressful in terms of abiotic environment,
      where the biomass and population density of birches were strongly reduced.
      Although neither overall ECM colonisation nor root fungal biomass showed stress
      related patterns, colonisation by Cenococcum geophilum tended to decrease with
      abiotic stress. ECM morphotype diversity declined with abiotic stress, and along
      altitudinal gradient this decline was related to an increase in proportion of
      morphotypes with high fungal biomass. Polycormic birches had higher ECM
      colonisation than monocormic birches at high stress sites only. ECM morphotype
      diversity increased with foliar nitrogen concentration at low stress sites, but
      not at high stress sites. Birches with higher chlorophyll fluorescence had lower
      chitin concentration in their roots (indicating lower proportion of fungal
      structures) at high stress sites only. Our results suggest that at high stress
      sites (1) mechanical shelter created by polycormic trees may favour ECM fungi and
      (2) mountain birches maintain lower ECM diversity than at low stress sites.

PMID- 18327654
TI  - Standard Snodgrass technique in conjunction with double-layer covering of the
      neourethra with dorsal dartos flap is the therapy of first choice for
      hypospadias.
AB  - PURPOSE: To evaluate the validity of the standard tubularized incised plate (TIP)
      urethroplasty technique for different kinds of hypospadia. MATERIALS AND METHODS:
      From June 2002 to December 2003 and from March 2006 to October 2007 38 patients
      aged 1-22 years (average 7.34) were operated using the concept of TIP
      urethroplasty. The hypospadiac meatus were subcoronal in 28 patients (73.68%),
      midshaft in six (15.78%), and penoscrotal in four (10.52%). Standard TIP
      urethroplasty in conjunction with double-layer covering of the neourethra with
      dorsal dartos flap were used in the primary cases (28 patients). In the secondary
      cases (four patients) and in boys who were circumcised before admission (six
      patients), modified TIP urethroplasty was used. The mean periods of
      hospitalization and follow-up were 0.92 days and 4.19 months, respectively.
      RESULTS: No fistulas were observed in boys who underwent primary reconstruction
      using standard TIP urethroplasty. Fistulas were observed in two patients (5.26%)
      one patient with penoscrotal hypospadias who underwent two-stage repair and
      another who was circumcised before admission. One patient had meatal stenosis at
      the early postoperative period which was corrected by dilatation of the external
      meatus at intervals up to 2 months postoperatively. CONCLUSION: Standard TIP
      urethroplasty with double-layer covering of the neourethra with dorsal
      subcutaneous tissue is the procedure of choice for treatment of primary cases of
      distal/midshaft hypospadias. This technique seems suitable for reconstruction of
      proximal, secondary, and even complicated hypospadias.

PMID- 18327655
TI  - Effect of hypothyroidism on the purinergic responses of corpus cavernosal smooth
      muscle in rabbits.
AB  - AIMS: Several studies have reported evidence of hormonal abnormalities in 25-35%
      of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men.
      In the present study, we examined purinergic relaxation responses in
      hypothyroidism in an experimental rabbit model and compared them with controls to
      evaluate the possible involvement of the purinergic pathway. MATERIALS AND
      METHODS: The study comprised 20 male New Zealand white rabbits. The rabbits were
      divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and
      adenosine precontracted with phenylephrine on the isolated corpus cavernosum
      preparations from control and hypothyroid rabbits. We also evaluated the effects
      of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus
      cavernosum preparations from control and hypothyroid rabbits. RESULTS: T3, T4,
      and testosterone levels were significantly lower in hypothyroid rabbits. ATP,
      alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced
      frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum
      strips precontracted with phenylephrine reduced significantly (P<0.05). Adenosine
      induced relaxation responses did not change significantly in hypothyroid rabbits.
      CONCLUSION: Reduction of relaxation response in hypothyroid rabbits corpus
      cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic
      nerves and endothelium.

PMID- 18327656
TI  - Combination of simvastatin administration and EPC transplantation enhances
      angiogenesis and protects against apoptosis for hindlimb ischemia.
AB  - The aim of this present study is to investigate the impacts of combinatorial
      simvastatin administration and endothelial progenitor cell (EPC) transplantation
      on therapeutic angiogenesis in an athymic nude mouse model of hind limb ischemia.
      Athymic nude mice were divided into four groups (n = 10/group): vehicle
      administration plus PBS injection (control), simvastatin administration plus PBS
      injection (simvastatin), vehicle administration plus EPC transplantation (EPC),
      and simvastatin administration plus EPC transplantation (combination). The
      combination therapy had the greatest laser Doppler blood perfusion imager (LDPI)
      index and capillary density among the four groups. Importantly, this combination
      therapy significantly reduced apoptosis of ischemic skeletal muscle cells in part
      through downregulation of Bax and upregulation of Bcl-2 compared with the other
      groups. Moreover, the combination therapy exhibited the highest efficacy of
      increasing the ratio of phospho-Akt to Akt among the four groups. Taken together,
      the simvastatin and EPC combination therapy promotes powerful angiogenesis in
      hindlimb ischemia. The combination therapy not only inhibites apoptosis of
      ischemic skeletal muscle cells partially via downregulation of Bax and
      upregulation of Bcl-2, but also activates Akt phosphorylation significantly.
      These efficacies may be mediated by the angiogenic potency of simvastatin, EPCs,
      and by the beneficial effects of simvastatin on transplanted EPCs as well.

PMID- 18327657
TI  - Chronic contamination of rats with 137 cesium radionuclide: impact on the
      cardiovascular system.
AB  - Cardiovascular system impairment has been observed in children and in liquidators
      exposed to the Chernobyl nuclear power plant accident. No experimental studies of
      animals have analyzed whether these disorders might be attributed to chronic
      ingestion of low levels of cesium 137 ((137)Cs). Biochemical, physiological, and
      molecular markers of the cardiovascular system were analyzed in rats exposed
      through drinking water to (137)Cs at a dose of 500 Bq kg(-1) (6500 Bq l(-1)).
      Plasma concentrations of CK and CK-MB were higher (+52%, P < 0.05) in
      contaminated rats. No histological alteration of the heart was observed, but gene
      expression was modified in the atria. Specifically, levels of ACE (angiotensin
      converting enzyme) and BNP (brain natriuretic peptide) gene expression increased
      significantly (P < 0.05). ECG analysis did not disclose any arrhythmia except ST-
      and RT-segment shortening (-9% and -11%, respectively, P < 0.05) in rats exposed
      to (137)Cs. Mean blood pressure decreased (-10%, P < 0.05), and its circadian
      rhythm disappeared. Overall, chronic contamination by an extreme environmental
      dose of (137)Cs for 3 months did not result in cardiac morphological changes, but
      the cardiovascular system impairments we observed could develop into more
      significant changes in sensitive animals or after longer contamination.

PMID- 18327658
TI  - Oligodendroglial cells and neurotrophins: a polyphonic cantata in major and
      minor.
AB  - Oligodendrocytes met neurotrophins in the early 1990s of the last century. Since
      then, their relationship underwent functional ups and downs partially dependent
      on the developmental stage of the oligodendroglial cells and the species, from
      which the cells were derived. This review provides a brief overview of
      oligodendroglial cells and neurotrophins, characterizes neurotrophin signaling
      during oligodendroglial development, and discusses the significance of
      proneurotrophins and sortilin for oligodendroglial death and survival.
      Furthermore, data are provided that TrkA, the tyrosine kinase competent NGF
      receptor, is localized to caveolincontaining microdomains on the oligodendroglial
      plasma membrane; an interplay of caveolin and NGF signaling via TrkA might be of
      functional importance. Finally, experimental evidence of studies is presented
      which support the idea that neurotrophins are promising candidates for improving
      oligodendroglial regeneration and remyelination.

PMID- 18327659
TI  - Stereotactic aspiration-thrombolysis of intracerebral hemorrhage and its impact
      on perihematoma brain edema.
AB  - BACKGROUND: Recent reports suggest that when thrombolytic agents are administered
      within the clot, lysis rate accelerates at the expense of increased risk of
      worsening edema. To test this hypothesis, we report on the volumetric analysis of
      (1) the intraparenchymal hematoma and, (2) perihematomal edema in a cohort of ICH
      patients treated with intraclot rtPA. METHODS: A convenience sample of highly
      selected ICH patients underwent frameless stereotactic aspiration and
      thrombolysis (FAST) of the clot. Two milligrams of rtPA were administered every
      12 h until ICH volume < or =10 cc, or catheter fenestrations were no longer in
      continuity with the clot. ICH and perihematomal edema volumes were calculated
      from CT scans. Using random effects linear regression we estimated the rate of
      hematoma and edema volume resolution as well as their relationship during the
      first 8 days of lytic therapy. RESULTS: Fifteen patients were treated, mean age:
      60.7 years, median time from ictus to FAST: 1 (range 0-3) day. Using a random
      effects model that considered volume resolution over the first 8 days following
      lytic therapy we found that the both percentage hematoma and percentage
      perihematoma edema resolution per day were quadratic with respect to time.
      Percentage residual hematoma volume on day K = 97.7% - [24.36%*K] + [1.89%*K
      (2)]; P < 0.001 for both terms. Percentage residual edema on day K = 97.4% -
      [13.94%*K] + [1.30%*K (2)]; P < 0.001 for K and P = 0.01 for K (2). Examination
      of each patient's volume data suggests that there exists a strong direct
      relationship between perihematoma edema volume and same day hematoma volume.
      CONCLUSIONS: In this cohort of ICH patients treated using FAST, volumetric
      analysis of ICH and perihematomal edema seems to suggest that local use of rtPA
      does not exacerbate brain edema formation. Furthermore, there seems to be a
      strong association between reduction in ICH volume and reduction in edema volume,
      as would be expected following the concept of "hemotoxicity" postulated by some
      investigators.

PMID- 18327660
TI  - Spontaneous cerebral air embolism associated with remote lung surgery.
AB  - INTRODUCTION: Airembolism without obvious trauma or surgery is rare. METHODS:
      Case report. RESULTS: Four years after resection of a non-small cell lung cancer,
      a 57-year-old man presented with recurrent episodes of sudden onset neurological
      deficits. Head computer tomographic (CT) scans suggested air embolism, and
      further investigations showed a potential anastomosis between a pulmonary air
      cavity and a pulmonary vein. He was treated surgically by debridement of the
      bronchovascular bundles surrounding the air cavity. The patient had no further
      neurologic deficits during 10 months of post-surgical follow-up. CONCLUSION: In
      the absence of trauma, sinus disease, recent surgery, or vascular procedures, the
      presence of air in the brain is unusual, and pulmonary sources of air embolism
      should be considered.

PMID- 18327661
TI  - Insular pathology in the at-risk mental state.

PMID- 18327662
TI  - Central role of dendritic cells in the regulation and deregulation of immune
      responses.
AB  - Dendritic cells (DCs) play a critical role in orchestrating the innate and
      adaptive components of the immune system so that appropriate, coordinated
      responses are mounted against infectious agents. Tissue-resident DCs interact
      with microbes through germline-encoded pattern-recognition receptors (PRRs),
      which recognize molecular patterns expressed by various microorganisms. Antigens
      use PRR activation to instruct DCs for the appropriate priming of natural killer
      (NK) cells, followed by specific T-cell responses. Due to the central role of DCs
      in regulating the activation and progression of immune responses, minor
      imbalances in the feedback control of Toll-like receptor (TLR)-activated cells
      have been associated with autoimmunity in genetically prone individuals. We
      review here recent findings on the role of DCs in the priming of innate and
      adaptive immune responses and the possible involvement of DCs in inducing and
      maintaining autoimmune reactions.

PMID- 18327663
TI  - Two-tiered hypotheses for Duchenne muscular dystrophy.
AB  - New approaches to understanding and designing treatments for Duchenne muscular
      dystrophy (DMD) may emerge from two hypotheses outlined here. The proposal that
      growing skeletal muscle is more susceptible to necrosis than adult muscle raises
      the possibility that less intensive treatments may be sufficient to protect
      muscles during the adult phase. The second proposal is that a different balance
      of cell and molecular events contributes to acute necrosis (e.g. resulting from
      exercise) compared with chronic damage of dystrophic muscle. Validation of such
      differences presents the potential for more specific targeting of drugs or
      nutritional interventions to events downstream of the dystrophin deficiency. A
      deeper understanding of the events arising as an early consequence of dystrophin
      deficiency in these two situations may strengthen approaches to therapy for DMD
      designed to improve muscle function and the quality of life.

PMID- 18327664
TI  - Host cell manipulation by the human pathogen Toxoplasma gondii.
AB  - Toxoplasma gondii is an obligate intracellular parasite that can infect virtually
      any nucleated cell. During invasion Toxoplasma creates the parasitophorous
      vacuole, a subcellular compartment that acts as an interface between the parasite
      and host, and serves as a platform for modulation of host cell functions that
      support parasite replication and infection. Spatial reorganization of host
      organelles and cytoskeleton around the parasitophorous vacuole are observed
      following entry, and recent evidence suggests this interior redecorating promotes
      parasite nutrient acquisition. New findings also reveal that Toxoplasma
      manipulates host signaling pathways by deploying parasite kinases and a
      phosphatase, including at least two that infiltrate the host nucleus. Toxoplasma
      infection additionally controls several cellular pathways to establish an anti
      apoptotic environment, and subverts immune cells as a conduit for dissemination.
      In this review we discuss these recent developments in understanding how
      Toxoplasma achieves widespread success as a human and animal parasite by
      manipulating its host.

PMID- 18327665
TI  - Abnormalities of vertebral formation and Hox expression in congenital
      kyphoscoliotic rats.
AB  - Scoliosis is a condition that involves an abnormal curvature and deformity of the
      spinal vertebrae. The genetic background and key gene for congenital scoliosis in
      humans are still poorly understood. Ishibashi rats (ISR) have congenital
      malformation of the lumbar vertebrae leading to kyphoscoliosis similar to that
      seen in humans. To understand the pathogenesis of congenital scoliosis, we have
      studied the abnormality of vertebral formation and the associated gene expression
      in ISR. Almost all ISR showed kyphosis or scoliosis of the lumbar vertebrae. In
      ISR with severe kyphosis, some vertebral disks were missing and some vertebral
      bodies were fused. Of the ISR, 27% showed hemi-lumbarization of lumbar and sacral
      vertebrae. Homeotic transformation of the first sacral vertebra into the seventh
      lumbar vertebra and the resultant loss of the fourth sacral vertebra were seen in
      half of the ISR. We also found unilateral fusions and deformities of primary
      ossification centers of the lumbar vertebral column in fetal ISR. Moreover, we
      observed that the expression levels of Hox10 and Hox11 paralogs in lumbo-sacral
      transitional areas of ISR were extremely low compared with those of normal rats.
      These results suggest that fusion of primary ossification centers in lumbar
      vertebrae in the embryonic period causes scoliosis and kyphosis and that Hox
      genes are involved in the occurrence of homeotic transformation in lumbo-sacral
      vertebrae of congenital kyphoscoliotic ISR.

PMID- 18327666
TI  - Effect of zinc on gene expression in osteoblastic MC3T3-E1 cells: enhancement of
      Runx2, OPG, and regucalcin mRNA expressions.
AB  - The effect of zinc sulfate on the mRNA expressions in Runx2, osteocalcin,
      alpha1(I) collagen, insulin-like growth factor-I (IGF-I), transforming growth
      factor-beta1 (TGF-beta1), osteoprotegerin (OPG), regucalcin, zinc transporter 1
      (ZIP1), or glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) in osteoblastic
      MC3T3-E1 cells in vitro was investigated. Cells with subconfluency were cultured
      for 48 h in a medium containing either vehicle or zinc sulfate (10(-6)-10(-4) M)
      without fetal bovine serum. Culture with zinc sulfate (10(-5) M) caused a
      significant increase in Runx2, OPG, or regucalcin mRNA expressions in the cells,
      while it did not have a significant effect on osteocalcin, alpha1(I) collagen,
      IGF-I, TGF-beta1, ZIP1, or G3PDH mRNA expressions. The effect of zinc sulfate
      (10(-4) M) in increasing Runx2 mRNA expression was seen at 24-72 h after culture.
      A significant increase in OPG mRNA expression was observed at 24 or 48 h after
      culture. Regucalcin mRNA expression was significantly increased at 48 or 72 h
      after culture with zinc sulfate (10(-4) M). The stimulatory effects of zinc
      sulfate on Runx2, OPG, or regucalcin mRNAs were significantly prevented in the
      presence of cycloheximide (10(-7) M), an inhibitor of protein synthesis, or 5,6
      dichloro-1-beta-D-ribofuranosyl-benzimidazole (10(-6) M), an inhibitor of
      transcription activity. Culture with beta-alanyl-L-histidinato zinc (10(-5) M)
      caused a significant increase in Runx2 or regucalcin mRNA expressions, while zinc
      acexamate (10(-5) M) did not have a significant effect on Runx2, OPG, ZIP1, or
      regucalcin mRNA expressions. This study demonstrates that zinc sulfate has a role
      in the enhancement of Runx2, OPG, or regucalcin mRNA expression in osteoblastic
      cells in vitro, suggesting its role in the regulation of gene expression in the
      cells.

PMID- 18327667
TI  - Potential problems inherent in cell-based stable NF-kappaB-GFP reporter systems.
AB  - The nuclear factor-kappaB (NF-kappaB) family of transcription factors plays a
      central role in numerous physiological processes including development, cell
      survival, immunity, and inflammation. We generated a series of stable clonal
      lines in mouse embryonic fibroblasts carrying NF-kappaB-GFP plasmid as a
      reporter. These cell lines were selected by flow cytometry for their high
      responsiveness to tumor necrosis factor (TNFalpha) or lipopolysaccharide (LPS),
      two classic NF-kappaB-inducing stimuli. Although all clones were generated from
      the same parental cell line, they each had a distinctive pattern of response to
      NF-kappaB stimuli. While exhibiting distinct profiles with regard to the GFP
      reporter, analysis of endogenous NF-kappaB downstream targets did not always show
      the same variability. This suggests that in the absence of confirmation of the
      signaling outcomes using endogenous outputs, considerable caution must be
      exercised in the interpretation of data using stable reporter systems.

PMID- 18327668
TI  - Polymorphism in environment responsive genes and association with Parkinson
      disease.
AB  - Attempts were made in the present case-control study to investigate the
      association of polymorphism in the genes encoding proteins involved in toxication
      detoxication and dopaminergic pathways and susceptibility to Parkinson's disease
      (PD). Seventy patients suffering from PD and one hundred healthy controls
      belonging to the same geographical location and same ethnicity were included in
      the study. PCR-RFLP and allele-specific PCR-based methodology were used to
      identify the genotypes. Multivariate logistic regression analysis revealed that
      heterozygous genotypes of cytochrome P4502D6*4(CYP2D6*4), CYP2E1*5B (RsaI)
      polymorphism and homozygous mutant genotypes of CYP2E1*6 (Dra1) were found to be
      overrepresented in PD cases when compared to the controls. Risk was also found to
      be increased in patients carrying glutathione S-transferase T1 (GSTT1) null or
      homozygous variant genotypes of GSTP1. Significant association was observed for
      monoamine oxidase-B(MAO-B) variant allele G and PD, whereas no difference in
      genotype and allele frequencies was observed for manganese-superoxide dismutase
      (MnSOD), dopamine receptor-D2(DRD2), and dopamine transporter (DAT) genes between
      controls and PD cases. Genotype combinations characterized by the presence of two
      variant genotypes on their corresponding loci revealed that four combinations of
      GSTT1 null and MnSOD(-9Val) or GST null and MAOB-G or CYP2E1*5B and MAO-B-AG or
      CYP2E1*5B and DRD2 (Taq1A-het) genotypes in the patients exhibited severalfold
      higher and significant association with risk to PD. Our data suggest that
      polymorphism in the genes involved in detoxification and dopamine regulation may
      modulate the susceptibility to PD and could be important risk factors in the
      pathogenesis of PD.

PMID- 18327669
TI  - Isolation and characterization of polymorphic microsatellite markers for the
      masked palm civet (Paguma larvata).
AB  - The masked palm civet (Paguma larvata) has been suspected to be the host of a
      SARS-like CoV virus that causes severe acute respiratory syndrome in humans. In
      China, the palm civet lives wild and is farmed, but even though the species is a
      potential carrier of the virus, its geographic distribution and genetic diversity
      have never been studied. We report the isolation and characterization of six
      polymorphic microsatellite markers for P. larvata. To characterize each locus,
      two farmed masked palm civet populations from Shanxi and Guangxi provinces in
      China were genotyped. The number of alleles per locus ranged from 3 to 15, and
      the observed heterozygosity for these populations was 47.1 and 68.7%,
      respectively.

PMID- 18327670
TI  - PET-based estradiol challenge as a predictive biomarker of response to endocrine
      therapy in women with estrogen-receptor-positive breast cancer.
AB  - PURPOSE: To determine if response to endocrine therapy of breast cancer can be
      predicted by either a metabolic "flare reaction" detected by positron emission
      tomography (PET) with 2-[(18)F]-fluoro-2-deoxyglucose (FDG), induced by an
      estradiol challenge, or by estrogen-receptor (ER) status, determined by PET with
      the estrogen analog 16alpha-[(18)F]fluoroestradiol-17beta (FES). METHODS: Fifty
      one post-menopausal women with advanced estrogen-receptor positive breast cancer
      were studied. Patients underwent FES-PET and FDG-PET at baseline and repeat FDG
      PET after 30 mg estradiol. Tracer uptakes was measured as the standardized uptake
      value (SUV). Patients were subsequently treated with either an aromatase
      inhibitor or fulvestrant. A prospectively defined cut-off SUV >or= 2 for FES was
      considered positive for ER expression. A cutoff of >or=12% increase in SUV for
      FDG, determined by ROC analysis, represented metabolic flare. PET results were
      correlated with responsiveness to endocrine therapy. RESULTS: Seventeen patients
      responded and 34 patients did not respond to endocrine therapy. Four responders
      and one non-responder had a clinical flare reaction, while only the responders
      demonstrated metabolic flare. After estradiol challenge, a significantly higher
      mean (+/-SD) percent change in SUV for FDG was noted in responders (20.9 +/-
      24.2) compared with non-responders (-4.3 +/- 11.0, P < 0.0001). On FES-PET, a
      higher tumor SUV was noted in responders (3.5 +/- 2.5) compared with non
      responders (2.1 +/- 1.8, P = 0.0049). There was significantly longer overall
      survival in patients with metabolic flare than in those without flare regardless
      of type of endocrine therapy (P = 0.0062). CONCLUSION: Baseline tumor FES uptake
      and metabolic flare after an estradiol challenge are both predictive of
      responsiveness to endocrine therapy in ER+ breast cancer.

PMID- 18327671
TI  - Molecular signatures of neoadjuvant endocrine therapy for breast cancer:
      characteristics of response or intrinsic resistance.
AB  - Approximately 30% of patients with estrogen receptor (ER) positive breast cancers
      exhibit de novo or intrinsic resistance to endocrine therapies. The purpose of
      this study was to define genes that distinguish ER+ resistant from ER+ responsive
      tumors, prior to the start of hormone therapies. Previously untreated post
      menopausal patients with ER+ breast cancers were treated for 4 months in a
      neoadjuvant setting with the aromatase inhibitor exemestane alone, or in
      combination with the antiestrogen tamoxifen. Matched pre- and post-treatment
      tumor samples from the same patient, were analyzed by gene expression profiling
      and were correlated with response to treatment. Genes associated with tumor
      shrinkage achieved by estrogen blockade therapy were identified, as were genes
      associated with resistance to treatment. Prediction Analysis of Microarrays (PAM)
      identified 50 genes that can predict response or intrinsic resistance to
      neoadjuvant endocrine therapy of ER+ tumors, 8 of which have been previously
      implicated as useful biomarkers in breast cancer. In summary, we identify genes
      associated with response to endocrine therapy that may distinguish ER+, hormone
      responsive breast cancers, from ER+ tumors that exhibit intrinsic or de novo
      resistance. We suggest that the estrogen signaling pathway is aberrant in ER+
      tumors with intrinsic resistance. Lastly, the studies show upregulation of a
      "lipogenic pathway" in non-responsive ER+ tumors that may serve as a marker of
      intrinsic resistance. This pathway may represent an alternative target for
      therapeutic intervention.

PMID- 18327672
TI  - Defining tetrahydrobiopterin (BH4)-responsiveness in PKU.

PMID- 18327673
TI  - Opioid detoxification via single 7-day application of a buprenorphine transdermal
      patch: an open-label evaluation.
AB  - RATIONALE: Managed withdrawal (i.e., detoxification) from opioid dependence is a
      widespread clinical procedure that is a necessary step for those pursuing
      abstinence. Buprenorphine is one effective detoxification treatment, however,
      consensus regarding effective detoxification procedures is lacking. OBJECTIVES:
      This study evaluated the efficacy of a buprenorphine transdermal formulation
      (i.e., patch) in suppressing opioid withdrawal, its safety and tolerability, and
      its biodelivery when applied for 7 days. METHODS: Physically dependent opioid
      (heroin) users (n = 12) completed a 10-day opioid detoxification in a residential
      research unit. Each received a single patch application that remained in place
      for 7 days. Blood samples were drawn prior to patch application and once daily
      thereafter. Assessments, four times daily, included: the amount of rescue
      medications ordered to treat withdrawal discomfort; self-report and observer
      ratings of opioid withdrawal and agonist effects; and vital sign measures.
      RESULTS: Overall, the patch appeared safe and well-tolerated. Buprenorphine
      plasma levels peaked 48 h after patch application at 0.59 ng/ml. Indices of
      withdrawal (self-reports, observer ratings, rescue medication) were significantly
      reduced within 24 h of patch application, continued to decline thereafter, and
      did not reappear following patch removal. CONCLUSIONS: This study confirms that
      transdermal buprenorphine is safe and clinically effective, and suggests that a 7
      day application may provide an effective and comfortable means of detoxification.
      This patch formulation would appear to be a useful opioid detoxification
      treatment by reducing compliance concerns, and administering buprenorphine in a
      formulation less likely to be diverted to illicit use.

PMID- 18327674
TI  - Intake and excretion of disodium monomethylarsonate in horses: a speciation
      study.
AB  - Capillary electrophoresis coupled to inductively coupled plasma mass spectrometry
      was used in a speciation study on disodium monomethylarsonate (DS-MMA(V)) and its
      metabolites in horses, to which the drug was administered by intramuscular
      injection on five consecutive days at a single arsenic dosage of 270 mg day(-1).
      Samples of urine, whole blood, plasma, and mane hair were analyzed before,
      during, and after drug administration. The data show that blood clearing and
      urinary excretion of MMA is a fast process following first-order kinetics with
      biological half-lives of about 38 h and 44 h for urine and plasma, respectively.
      In the time period of 9 days studied, the only metabolite detected in urine was
      dimethylarsinic acid (DMA(V)), which 4 days after the last drug administration
      accounted for up to 75% of the total excreted arsenic species. This shows, for
      the first time, that biomethylation of MMA(V) to DMA(V) is the principal
      metabolic pathway of this drug in horses. Although DS-MMA(V) was administered
      only during a short 5-day period, an up to six fold increase of arsenic could be
      measured in the newly grown mane hair.

PMID- 18327675
TI  - Automated normal phase nano high performance liquid chromatography/matrix
      assisted laser desorption/ionization mass spectrometry for analysis of neutral
      and acidic glycosphingolipids.
AB  - The coupling of nano high-performance liquid chromatography (nanoHPLC) with
      matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) via an
      automatic spotting roboter was developed and adapted for the first time for the
      analysis of complex mixtures of glycosphingolipids (GSLs). The 2,5
      dihydroxybenzoic acid and 6-azo-2-thiothymine matrix systems were adjusted to
      concurrently meet the requirements for reproducible and homogeneous crystal
      formation with the liquid chromatography (LC) eluent under the variable LC
      solvent composition over the course gradient and high ionization efficiency of
      the GSL species, without the need for recrystallization. Precise adjustment of
      the automatic spotting parameters in terms of matrix flow rate, on-tip collection
      time of the matrix/LC eluent solution and the matrix spotting mode, i.e.,
      continuous and discontinuous, was accomplished to collect individually nanoHPLC
      separated species within distinct spots and consequently recover by MALDI MS
      screening all major and minor GSL species in the mixtures. The nanoHPLC/MALDI MS
      coupling protocol was developed and applied to a mixture of neutral GSLs purified
      from human erythrocytes and a monosialoganglioside mixture expressed by the
      murine MDAY-D2 cell line. Additionally, on-line nanoHPLC/MALDI doping with
      lithium cations of individually separated neutral GSLs was introduced to enhance
      data interpretation of the GSL MS pattern, while preserving the same level of
      information and ultimately to enhance structural assignment of components of
      interest. The method is demonstrated to be highly sensitive, reaching the low
      femtomole level of detection of individual GSL species and is highlighted as a
      versatile analytical tool for glycolipidomic studies. [figure: see text]

PMID- 18327676
TI  - Combined use of carbon nanotubes and ionic liquid to improve the determination of
      antidepressants in urine samples by liquid chromatography.
AB  - Antidepressants are widely used for the treatment of psychiatric disorders and
      therefore their monitoring in biological fluids is quite important taking into
      account that they can produce dangerous biochemical imbalances in toxic doses. A
      method for the determination of antidepressants in urine samples is presented
      using solid-phase extraction (SPE) and high-performance liquid chromatography
      (HPLC) with ultraviolet (UV) detection. Home-made cartridges containing 30 mg
      multiwall carbon nanotubes are employed for isolation of the analytes from the
      sample, allowing also the preconcentration of the analytes prior to the HPLC
      analysis. Chromatographic separation was achieved in a reversed-phase C(8) column
      using the ionic liquid 1-butyl-3-methylimidazolium trifluoromethanesulfonate as
      silanol activity suppressor, which enhances peak symmetry and chromatographic
      resolution. Limits of detection were 12.3 ng mL(-1) for trazodone and 90.1 ng mL(
      1) for fluoxetine. The repeatability of the proposed method expressed as RSD (n =
      11) varied between 3.4% (fluoxetine) and 5.0% (desipramine and mianserine). Thus,
      the method is suitable for the therapeutic monitoring of antidepressants in urine
      samples.

PMID- 18327677
TI  - SF-6D versus EQ-5D: reasons for differences in utility scores and impact on
      reported cost-utility.
AB  - The choice of instrument (e.g. EQ-5D vs. SF-6D) can lead to different health
      related utility scores, but it is unclear why these differences arise and whether
      they change cost utility analysis (CUA) results. This paper addresses these
      issues using a case study where using SF-6D rather EQ-5D led to greater utility
      gain and a lower cost per QALY for treatment. The paper examines reasons for this
      difference. This paper finds that an important factor was the inclusion in the SF
      6D descriptive system of separate items for "vitality" and "social functioning",
      not explicitly included in EQ-5D. Further studies are required that examine the
      impact of the choice of instrument on cost-utility.

PMID- 18327678
TI  - Basiliximab induction therapy for live donor kidney transplantation: a long-term
      follow-up of prospective randomized controlled study.
AB  - BACKGROUND/AIMS: The effect of basiliximab induction therapy on long-term patient
      and graft survival is not yet clear. We aimed to evaluate if there is any
      advantage of routine basiliximab induction on the long-term outcome of living
      related donor kidney transplantation. METHODS: One hundred adult recipients with
      their first kidney allograft were randomized into two treatment groups, one group
      received basiliximab and the second served as a control. All patients received a
      maintenance triple immunosuppressive therapy (steroids, cyclosporine (CsA) micro
      emulsion and azathioprine) and were followed up thoroughly for 7 years. RESULTS:
      Basiliximab significantly reduced the proportion of patients who experienced
      acute rejection in the first year (18/50) when compared to the control group
      (31/50), and in 7 years (28/50) when compared to (37/50) in controls. The
      cumulative steroid dose used throughout the whole study period was significantly
      lower in the basiliximab group. The overall incidence of post-transplant
      complications was comparable among the two treatment groups. There was no
      significant difference in patient or graft survival; 7 years patient and graft
      survival were 92, 76% for basiliximab and 92, 80% for the control group,
      respectively. CONCLUSION: Routine basiliximab induction significantly reduced the
      incidence of acute rejection without any noticeble beneficial effect on the long
      term renal transplantation outcome.

PMID- 18327679
TI  - Primary histiocytic sarcoma of the spleen associated with hemophagocytosis.
AB  - We report a patient with primary histiocytic sarcoma of the spleen associated
      with prominent hemophagocytosis. Although thrombocytopenia, probably due to
      hemophagocytosis, was refractory to corticosteroid therapy, the transfusion of
      platelets, and splenic irradiation, partial splenic embolization was effective
      and facilitated splenectomy for a diagnosis. The majority of the spleen showed
      necrosis, but viable neoplastic cells with pleomorphic nuclei and abundant
      cytoplasm, showing occasional erythrocytes or leukocytes, were still discernible.
      The neoplastic cells expressed CD68, lysozyme, and S-100 protein, and were
      negative for lymphoid, myeloid, and epithelial cell markers. CD163, a
      monocyte/macrophage-specific molecule, was positive in only some of them. Despite
      multiagent chemotherapy, the patient died of the disease, showing a rapidly
      progressive clinical course. Although the preoperative diagnosis of primary
      splenic histiocytic sarcoma is difficult, it has been confirmed in patients with
      splenomegaly of unknown etiology that clinicolaboratory features suggestive of
      hemophagocytosis may be important clues suggestive to the disease. CD163
      expression by neoplastic cells could be confirmed only after careful observation,
      because the molecule may only be seen in some of the neoplastic cells.

PMID- 18327680
TI  - Bile aspiration for diagnosis of Candida glabrata cholecystitis.

PMID- 18327681
TI  - Prevalence and risk factors for nosocomial infections in hospitals of the Veneto
      region, north-eastern Italy.
AB  - OBJECTIVE: The study aimed to assess prevalence and risk factors for nosocomial
      infection (NI) in 21 hospitals of the Veneto Region (Italy). METHODS: In May
      2003, a one-week-period prevalence study of NI was carried out in 21 hospitals,
      representing 63% of all hospital beds for acute patients of the Veneto Region.
      Intensive care units represented 84% of all intensive care beds of the Region.
      Long term care, neonatal intensive care, burn, psychiatric and dermatology units
      were excluded. RESULTS: Overall, 6,352 patients were surveyed. The prevalence of
      NI was 7.6% (range 2.6%-17.7%), while 6.9% of patients (range 2.6%-15.5%) were
      affected by at least one NI. The prevalence of patients with NI in medical,
      surgical and intensive care areas was 6.6%, 5.0% and 25.8%, respectively. The
      sites most frequently affected were the following: urinary tract (28.4%),
      surgical site (20.3%), blood stream (19.3%), pulmonary and lower respiratory
      tract (17.6%). At multivariate analysis risk factors independently associated to
      NI were: Charlson index score >1, severity of underlying disease, exposure to
      antibiotics, surgical intervention, trauma at admission, presence of central
      venous catheter >24 h, urinary catheter, intubation, tracheostomy, and duration
      since admission >15 days. CONCLUSION: The study provided baseline data of NI in
      the Veneto Region hospitals. It showed that NI are frequent, and display a wide
      inter-hospital variability of rates. The highest prevalence has been reported in
      intensive care units. The unusual high frequency of blood stream infections and
      the relatively lower prevalence rate of surgical site infections highlighted the
      limits of prevalence studies.

PMID- 18327682
TI  - Atypical localization of Leishmaniasis in an intestinal polyp.

PMID- 18327683
TI  - Post-kala-azar dermal Leishmaniasis and uveitis in an HIV-positive patient.

PMID- 18327684
TI  - Treatment of a large left main coronary artery thrombus by aspiration
      thrombectomy.
AB  - A left main coronary artery thrombosis is a life-threatening condition demanding
      immediate therapeutic management. Traditional treatment options include
      thrombolysis, percutaneous coronary intervention (PCI) with stenting or cardiac
      bypass surgery. The number of reported cases in which aspiration thrombectomy has
      been used is limited. Indications for this therapeutic approach are determined by
      coronary anatomy, clinical stability, and hemodynamic condition of the patient.
      We present the case of an acute left main coronary artery thrombosis leading to
      progressive deterioration of left ventricle function that was successfully
      treated with aspiration thrombectomy.

PMID- 18327685
TI  - Phytoaccumulation prospects of cadmium and zinc by mycorrhizal plant species
      growing in industrially polluted soils.
AB  - The natural vegetation growing along a wastewater channel was subjected to
      analyze the uptake of Cadmium (Cd) and Zinc (Zn) and their subsequent
      accumulation in aboveground and underground plant parts. Species which were
      mycorrhizal and growing in soils receiving industrially contaminated wastewater
      were collected along with their rhizospheric soil samples. The nearby
      uncontaminated control (reference) area was also subjected to sampling on similar
      pattern for comparison. Both Cd and Zn concentrations were significantly higher
      in soils of the study area as compared to the reference site. Five plant species
      i.e. Desmostachya bipinnata, Dichanthium annulatum, Malvastrum coromandelianum,
      Saccharum bengalense, and Trifolium alexandrinum were analyzed for metal uptake.
      The maximum phytoaccumulation of Cd was observed in Desmostachya bipinnata (20.41
      microg g(-1)) and Dichanthium annulatum (15.22 microg g(-1)) for shoot and root
      tissues, respectively. However, Malvastrum coromandelianum revealed maximum Zn
      accumulation for both the shoot and the root tissues (134 and 140 mug g(-1),
      respectively). The examination of cleared and stained roots of the plants from
      both the areas studied revealed that all of them were colonized to a lesser or a
      greater degree by arbuscular mycorrhizal (AM) fungi. The Cd hyperaccumulating
      grasses i.e. Desmostachya bipinnata and Dichanthium annulatum, from study area
      had smaller root:shoot (R/S) ratio as compared to those growing on reference area
      indicating a negative pressure of soil metal contamination. The lower R/S ratio
      in the mycorrhizal roots observed was probably due to increased AM infection and
      its mediatory role in soil plant transfer of heavy metals. Furthermore,
      comparatively lower soil pH values in the study areas may have played a key role
      in making the overall phytoavailability of both the metals. Consequently
      variations in Cd and Zn tissue concentration among species were observed that
      also indicate the phytoaccumulation potential of the native species.

PMID- 18327686
TI  - Mechanisms of adaptive angiogenesis to tissue hypoxia.
AB  - Angiogenesis is mostly an adaptive response to tissue hypoxia, which occurs under
      a wide variety of situations ranging from embryonic development to tumor growth.
      In general, angiogenesis is dependent on the accumulation of hypoxia inducible
      factors (HIFs), which are heterodimeric transcription factors of alpha and beta
      subunits. Under normoxia, HIF heterodimers are not abundantly present due to
      oxygen dependent hydroxylation, polyubiquitination, and proteasomal degradation
      of alpha subunits. Under hypoxia, however, alpha subunits are stabilized and form
      heterodimers with HIF-1beta which is not subject to oxygen dependent regulation.
      The accumulation of HIFs under hypoxia allows them to activate the expression of
      many angiogenic genes and therefore initiates the angiogenic process. In recent
      years, however, it has become clear that various other mechanisms also
      participate in fine tuning angiogenesis. In this review, I discuss the
      relationship between hypoxia and angiogenesis under five topics: (1) regulation
      of HIF-alpha abundance and activity by oxygen tension and other conditions
      including oxygen independent mechanisms; (2) hypoxia-regulated expression of
      angiogenic molecules by HIFs and other transcription factors; (3) responses of
      vascular cells to hypoxia; (4) angiogenic phenotypes due to altered HIF signaling
      in mice; and (5) role of the HIF pathway in pathological angiogenesis. Studies
      discussed under these topics clearly indicate that while mechanisms of oxygen
      regulated HIF-alpha stability provide exciting opportunities for the development
      of angiogenesis or anti-angiogenesis therapies, it is also highly important to
      consider various other mechanisms for the optimization of these procedures.

PMID- 18327687
TI  - [Nosocomial urinary tract infections in the geriatric hospital - pathogen
      spectrum and resistancies].
AB  - We examined 834 isolates of urinary cultures (26 fungi and 808 isolates from 28
      bacteria) in an academic geriatric teaching hospital for microbial spectrum and
      resistance analysis. Of the bacteria, 90% were associated to ten species.
      Detection rate of MRSA and ESBL was 1%, detection rate for pseudomonas
      aeruginosa, proteus species, coagulase negative staphylococci and klebsiella
      species were higher than in an university clinic (p < 0.001). Resistency rates
      were high for the 10 most frequent bacteria: 53.3% of cross-tabulations between
      bacterium and antibiotic agent (sulfamethoxazol-trimethoprim, amoxicillin
      clavulanate, ciprofloxacin, moxifloxacin, cefuroxim, imipenem) showed resistency
      rate higher than 10%. We assume that specific factors of geriatric sample taking
      have an impact to our 2-year resistogram results. It is necessary to combine data
      analysis from comprehensive geriatric assessment and microbiological methods.

PMID- 18327688
TI  - [External validity of clinical trials for treatment of dementia with ginkgo
      biloba extracts].
AB  - OBJECTIVES: Ginkgo bilobaextracts have been applied in the treatment of dementia
      of vascular origin and Alzheimer disease for a long time. However, in the most
      elaborated systematic review to date, Birks and colleagues drew quite a moderate
      conclusion in spite of the overall positive results. The reason for such a
      moderate interpretation often lies in the preference of internal validity such as
      randomisation and blinding, sometimes at the expense of external validity
      (conditions of everyday practice). Because of this, we analysed the clinical
      trials evaluated by Birks et al. in the light of the following questions: 1) To
      what extent are criteria of external validity considered? 2) Does the additional
      evaluation of external validity lead to differences in the estimation of
      efficacy? 3) What are the results of our analysis in regard to the efficacy of
      ginkgo biloba extract? MATERIAL AND METHODS: The selection of the clinical trials
      was based upon those included in the review carried out by Birks et al. (2002).
      The criteria for evaluating external validity were developed by consulting
      physicians specialised in geriatrics, experts in herbal pharmaceutics and
      affected/ related individuals (patients and relatives). RESULTS: We analysed 34
      placebo-controlled clinical trials with a total of 37 comparisons. 21 trials
      showed significant results in favour of the ginkgo application in more than 50%
      of investigated outcome parameters, eight were significant for less than 50% of
      the parameters, four showed a trend in favour of ginkgo, and only two studies
      (with 4 comparisons) found no advantage for ginkgo. One of these negative studies
      used daily doses far below the usual dose range [corrected] We found no evidence
      for publication bias. None of the studies considered all criteria of external
      validity. Out of the seven studies with relatively high external validity and
      good overall quality, five showed a significant result in more than 50% of
      parameters, two in < or = 50%. Severe adverse effects were not mentioned in the
      studies. DISCUSSION AND CONCLUSIONS: 1) In the clinical studies analysed external
      validity was taken into account only moderately, especially with respect to
      additional non-pharmaceutical interventions and selection of participants. 2) The
      evaluation according to external validity led to a different selection of studies
      that were used for estimation of the ginkgo efficacy without effects on the
      overall result. 3) Sufficient evidence of the efficacy of ginkgo bilobaextracts
      in the treatment of dementia of vascular origin and Alzheimer disease is provided
      in spite of methodological limitations. Further studies should focus on
      effectiveness, ginkgo-sensitive subgroups, more individualised therapeutic goals
      and corresponding outcome measurements.

PMID- 18327689
TI  - [Ageing and the elderly in Turkey--results of the first age report from Turkey].
AB  - Although Turkey is generally considered a "young country," we already have the
      early signs of demographic ageing. By 2020, the percentage of the Turkish
      population above the age of 60 will be close to 20%. This article examines the
      important aspects of Turkish demographic structure and discusses the general life
      conditions of the elderly. All data are from a report published by the author
      about the life conditions of the elderly in Turkey. This report showed that, in
      Turkey, ageing is generally specific to female elderly. Poverty during elderly
      age should be considered the most serious problem both today and in the future,
      although this issue shows a great diversity in terms of occupational status,
      educational level and regions. Care for the elderly is not a major problem yet.
      However, Turkish society needs to prepare for future problems in elderly care by
      creating the necessary legal and political infrastructure. Education and research
      about social gerontology has not improved yet. There needs to be great
      improvement in this field to come to the general developmental level in Europe.

PMID- 18327690
TI  - Predictors for occasional and recurrent falls in community-dwelling older people.
AB  - BACKGROUND: Little is known about the prevalence of falls and the related risk
      factors in the general population of community-living older people in Germany.
      OBJECTIVES: To assess the prevalence and related predictors of different types of
      falls in a sample of community-dwelling 65 years and older people in Germany
      living in a metropolitan area. Study design and setting prospective cohort study
      in 622 community dwelling people aged > or =65 years. RESULTS: A total of 107
      persons (17.2%) reported falling at least once (occasional fallers), while 36
      (5.7%) experienced two or more falls (recurrent fallers) in the last 6 months.
      Main predictors for all fallers were age (OR 1.8; 95% CI 1.1-3.0), being female
      (OR 1.7; 95% CI 1.1-2.2), living alone (OR 1.9; 95% CI 1.2-2.9), poor health
      status (OR 3.3; 95% CI 2.1-5.3), varifocals (OR 1.7; 95% CI 1.0-3.1), disturbance
      of memory (OR 1.7; 95% CI 1.0-3.0), depression (OR 4.8; 95% CI 2.5-9.2), sleep
      disturbances (OR 2.7; 95% CI 1.7-4.3), incontinence (OR 2.1; 95% CI 1.3-4.9),
      dizziness (OR 3.0; 95% CI 1.9-5.0), 3 medical conditions or more (OR 3.3; 95% CI
      2.1-5.1), lower physical functioning and mobility. Two of the strongest
      predictors were reported falls (OR 4.9; 95% CI 3.1-7.7) and recurrent falls (OR
      10.0; 95% CI 5.0-20.0) in the last 6 months. CONCLUSION: Older adults living at
      home should be screened for falls in history and problems in gait and mobility in
      any anamnesis to identify those who are at risk for falls.

PMID- 18327691
TI  - [Reality of psychotherapeutic care with regard to outpatient psychotherapy of
      elderly people in Munsterland (Westfalia)].
AB  - The need for efficacy of geriatric psychotherapy as well specialized training in
      geriatric psychosomatics and psychotherapy is commonly recognized amongst
      professionals. Despite this, this knowledge is not reflected in everyday life.
      One consequence of this is that psychotherapy for elderly patients is still the
      exception. We conducted a study in which 478 practicing psychotherapists in
      Munsterland (Westfalia) were surveyed by mail questionnaire regarding the number
      and main diagnosis of their patients of greater than 50 years of age, as well as
      the elderly-specific therapies or future plans for such therapies they might
      have. The response rate was 65% (312 psychotherapists who answered the
      questionnaire). The results showed that patients older than 60 years of age were
      greatly underrepresented compared to younger patients. Moreover, specific
      therapies, such as age-specific psychotherapy in groups, were rare. To date, it
      seems that only a minority of elderly patients with psychiatric and psychosomatic
      diseases are treated adequately by psychotherapy in the outpatient sector. This
      was evident even in a region such as Munsterland, which has plentiful
      psychotherapeutic resources.

PMID- 18327692
TI  - [German adaptation of the "Activities-Specific Balance Confidence (ABC) scale"
      for the assessment of falls-related self-efficacy].
AB  - The present study investigates the psychometric properties and the factorial
      structure of the German adaptation of the Activities-Specific Balance Confidence
      (ABC) scale (Powell & Myers, 1995) for the evaluation of falls-related self
      efficacy in community-dwelling older adults. The German adaptation of the ABC
      using a forward-backward procedure was administered to 113 older adults (age
      68.9+/-8.5 years). The following internationally accepted instruments were used
      for validation: The Short Form Health Survey SF 36, the Geriatric Depression
      Scale (GDS), the Trail Making Test and the Letter Number Sequencing Test, and
      motor tests (balance, strength, mobility). The internal consistency (0.91-0.95)
      as well as the test-retest reliability of the subscales was excellent (0.94
      0.98). The correlation coefficients with the validation instruments ranged
      between 0.33 and 0.58. Significant differences in the ABC-D scores were found in
      older adults with and without falls. Older adults with a recent fall history
      scored lower on the ABC-D than older adults without a recent fall history. To
      conclude, the German version of the ABC has properties analogous to the original
      English version and is apparently useful in assessing falls-related self
      efficacy.

PMID- 18327693
TI  - [CSF levels of total tau protein in patients with mild cognitive impairment and
      Alzheimer's disease].
AB  - In recent studies, patients diagnosed with Alzheimer's disease (AD) showed
      significantly elevated CSF levels of tau protein. Tau protein was therefore
      regarded as a putative molecular marker for AD. Since early diagnosis of AD is
      warranted for appropriate therapeutic intervention, investigation of total tau
      protein levels in patients with Aging Associated Cognitive Decline (AACD) and AD
      are reasonable. In our study the CSF concentrations of total tau protein were
      measured by ELISA in 132 patients with AD, 29 patients with AACD and 24 healthy
      controls. CSF concentrations were compared between the subgroups of mild,
      moderate and severe AD, AACD and the control group and were correlated with age
      and severeness of the illness. The concentration of total tau protein was
      increased significantly in patients with severe and moderate AD compared to all
      other groups. Within the group of AD patients, total tau protein correlated
      significantly with the severity of the dementia but not with age. Although the
      range of the measured tau protein concentrations is wide and overlapping between
      the diagnostic groups our data indicate that from a clinical point of view
      significantly increased tau protein levels confirm the clinical diagnosis of AD
      while normal values do not exclude it.

PMID- 18327694
TI  - [Loss of olfaction with aging: a frequent disorder receiving little attention].
AB  - Loss of olfaction in old age is a frequent problem, which occurs at the same
      frequency as diabetes or severe sensorineural hearing loss. Problems caused by
      loss of the sense of smell may include weight loss due to loss of appetite,
      intake of rotten foods, social isolation and depression. Until now the loss of
      olfactory function has received relatively little attention compared to diabetes
      or hearing loss. In this article we review the loss of the sense of smell with
      age. Possible therapies are discussed to improve the quality of life in older
      people.

PMID- 18327695
TI  - Small-bowel tumors in the elderly 65+ years: 10 years of experience.
AB  - Primary, secondary, benign or malignant tumorous diseases of the small intestine
      are rare. They are very often diagnosed by accident or as a cause of acute
      abdomen. Less serious symptoms can be overseen mainly in older patients. This
      work represents a prospective evaluation of a diagnostic and therapeutic
      algorithm in the management of the small-intestine tumor below the ligamentum
      Treitzi in patients over 65 years of age. RESULTS: A population of 96 patients
      who underwent surgery for a small-intestinal tumor in our hospital from 1996 to
      2006 is presented. Thirty-four of these patients were older than 65 years.
      Ultrasound of the small intestine was sufficient to make the diagnosis in 21 of
      them. Elective surgery (laparoscopy was highly preferred) could be offered to 31
      of these older patients. Perioperative mortality was zero. CONCLUSION: The small
      bowel ultrasound can be recommended as the first choice method. All complaints
      regarding the gastrointestinal tract should be verified. Older patients can be
      safely offered an elective laparoscopic surgery with acceptable morbidity and
      mortality.

PMID- 18327696
TI  - [Instrument for the assessment of middle-aged and older adults' physical
      activity: design, eliability and application of the German-PAQ-50+].
AB  - Existing physical activity questionnaires have focused either on young and middle
      aged adults or on the elderly. They have mainly assessed only a portion of
      possible physical activities or contained nation-specific sports. As there is no
      gold standard for a questionnaire-based assessment of physical activity in the
      over-50 population, recommendations for such a questionnaire relating to German
      speaking countries were developed. This work included a systematic literature
      research, a survey of experts, and the design of a questionnaire based on
      validated measuring instruments. Finally, to test its reliability and application
      in the field, the complete questionnaire, including a retest, was applied by
      telephone interview (n = 57). The test-retest-correlation was r = 0.60 for the
      total time of physical activity and r = 0.52 for total energy expenditure. The
      researchers determined that the instrument is comprehensive in its coverage of
      all relevant domains of physical activity for the over-50 population; it is
      economically feasible and showed good acceptance.

PMID- 18327697
TI  - Hemodialysis in patients older than 65 years with end-stage renal failure-
      comparison of outcome in patients with and without diabetes.
AB  - BACKGROUND: During recent years, the number of patients with end-stage renal
      disease (ESRD) has been rising worldwide. Especially older patients and those
      with diabetes contribute to this rise. The aim of the present study was to
      evaluate whether patients older than 65 years with type 2 diabetes, who started
      first dialysis, have a higher prevalence of vascular diseases and co-morbidities,
      show a higher incidence of vascular complications and/or have a higher mortality
      rate than elderly non-diabetic patients with ESRD. PATIENTS AND METHODS: In this
      study, 82 consecutive patients with ESRD, who had either type 2 diabetes or did
      not have diabetes and who had started chronic hemodialysis (HD) in our dialysis
      center during the years 1994 to 2002, were included. Patients were included when
      they were older than 65 years. Patients were divided into two groups: those with
      diabetes (DM) (n = 47) and those without diabetes (nDM) (n = 35). For both groups
      the number of co-morbidities as well as the prevalence of vascular diseases and
      vascular risk-factors at the start of HD was evaluated. In addition, the
      incidence of vascular complications was registered over a 3-year observation
      period. In both groups serum(S)-creatinine, blood urea nitrogen (BUN), creatinine
      clearance, hemoglobin, fasting blood glucose, HbA1c (in diabetic patients),
      cholesterol, triglycerides and phosphorus were evaluated. RESULTS: At the start
      of HD the creatinine clearance was significantly higher in diabetic subjects (nDM
      7.1 +/- 2.1 vs DM 9.5 +/- 4.4 ml/min/1.73 m2; p < 0.005). For S-creatinine the
      difference was not statistically significant (nDM 8.7 +/- 3.3 mg/dl vs DM 7.4 +/-
      2.4; p = 0.07). Fasting blood glucose was significantly higher in diabetic
      patients (p < 0.001). BUN, hemoglobin, phosphorus and lipids were not
      significantly different in both groups. There was no statistically significant
      difference in systolic or diastolic blood pressure, but a higher amount of
      antihypertensive drugs were necessary in the DM group for blood pressure control
      (p < 0.01). In both groups there was a high prevalence of vascular diseases at
      the start of HD. In the diabetic patients the prevalence of peripheral vascular
      disease was significantly higher. Furthermore, in the first and second year
      significantly more vascular complications were observed in the DM group (p <
      0.01). Survival was low in both groups. The 3-year survival was 20.0% in non
      diabetic and 17.0% in diabetic patients (NS). CONCLUSION: Patients older than 65
      years with ESRD have a low survival with and without type 2 diabetes. The
      mortality rate was only slightly higher in the diabetic group and was not
      statistically significant. The prevalence of vascular diseases and co-morbidities
      is high in both groups; however, the incidence of cardiovascular complications
      was significantly higher in our diabetic patients.

PMID- 18327698
TI  - [Clinical assessment of oral health between physician and dentist--a pilot study
      on inter-examiner reliability].
AB  - OBJECTIVE: Very little is known about the ability of physicians to assess oral
      health of geriatric patients. The aim of this pilot study was to assess the in
      ter-examiner reliability in assessment of oral health for a dentist and a
      physician, and to evaluate the influence of training in dental findings for the
      physician on inter- examiner reliability. METHODS: Inter-examiner reliability
      between a physician and a dentist was tested in a primary geriatric hospital with
      126 participants 60 years old or more (mean 77 years; 32% men) using the Revised
      Oral Assessment Guide (ROAG) and additional items relating to caries and dentures
      (14 items). Calculated were kappa-coefficients, and percentage agreement between
      the examiners before (n = 50) and after (n = 51) training for the physician in
      dentistry (n = 25 for the common training session). RESULTS: Before the training
      both kappa-values and percentage agreement were not acceptable in the different
      categories. After the training, with the exception of the categories swallow and
      tongue, the reliability of all items was moderate or good. The number of
      occasions on which the physician underestimated the clinical finding compared to
      the dentist - indicating a clinical finding was overlooked - decreased for every
      item; for retention of denture and decayed teeth this decrease was significant.
      CONCLUSION: Screening for oral health performed by a physician was insufficient
      regarding the different clinical aspects. Training in the use of an oral health
      assessment tool improved the reliability of the screening. Because of the low
      number of examiners the results should be interpreted as a pilot investigation on
      this new topic.

PMID- 18327699
TI  - [Assessment of patient satisfaction in geriatric hospitals: a methodological
      pilot study].
AB  - The assessment of patient satisfaction using mailed questionnaires is an
      established method of quality management in acute care hospitals in our health
      care system. The needs of aged patients and the inter-professional approach of
      geriatric medicine are, however, not taken into account by such surveys. To date,
      validated German instruments to assess patient opinions in geriatric in-hospital
      care are rare. We report the results of a multi-center feasibility study of a
      questionnaire developed especially for such needs. We examined 1918 patients with
      a median age of 82 years and a mean Mini- Mental Score (MMS) of 25 points in 3
      Swiss geriatric hospitals. We examined the results of all completed written
      questionnaires for their psychometric properties. In parallel, we assessed the
      satisfaction of the patient's spouses or family members applying the same
      instrument. The return rate was 32% when the instrument was applied as a
      questionnaire and 60% when applied as an interview. In questionnaires, the return
      rate was dependent on cognition with lower return in patients with low MMS
      scores. The return rate of questionnaires mailed to family members was 35%. The
      theoretical construct patient satisfaction was reliable and valid. The Cronbach
      Alpha values in different item areas ranked between 0.67 (hotel services, room
      quality) and 0.92 (physicians). We were not able to assess the quality of medical
      therapies and of pain treatment due to low answer frequencies. Overall, patients
      were satisfied with all medical services in the participating hospitals. In
      contrast, satisfaction was low in family members regarding the quality of
      information flow between family members and physicians or nurses. CONCLUSIONS: An
      instrument to assess patient opinions can easily be introduced into a geriatric
      hospital. Such an instrument can provide important information for the
      improvement of quality in different areas of geriatric care such as medical,
      nursing care or guest services.

PMID- 18327700
TI  - Anthocyanins inhibit peroxyl radical-induced apoptosis in Caco-2 cells.
AB  - The antioxidant activity of anthocyanins has been well characterized in vitro;
      many cases has been postulated to provide an important exogenous mediator of
      oxidative stress in the gastrointestinal tract. The objective of this study was
      to evaluate the efficacy of anthocyanin protection against peroxyl radical (AAPH)
      induced oxidative damage and associated cytotoxicity in Caco-2 colon cancer
      cells. Crude blackberry extracts were purified by gel filtration column to yield
      purified anthocyanin extracts that were composed of 371 mg/g total anthocyanin,
      90.1% cyanidin-3-glucoside, and 4.9 mmol Trolox equivalent/g (ORAC) value. There
      were no other detectable phenolic compounds in the purified anthocyanin extract.
      The anthocyanin extract suppressed AAPH-initiated Caco-2 intracellular oxidation
      in a concentration-dependent manner, with an IC50 value of 6.5+/-0.3 microg/ml.
      Anthocyanins were not toxic to Caco-2 cells, but provided significant (P<0.05)
      protection against AAPH-induced cytotoxicity, when assessed using the CellTiter
      Glo assay. AAPH-induced cytoxicity in Caco-2 cells was attributed to a
      significant (P<0.05) reduction in the G1 phase and increased proportion of cells
      in the sub G1 phase, indicating apoptosis. Prior exposure of Caco-2 cells to
      anthocyanins suppressed (P<0.05) the AAPH-induced apoptosis by decreasing the
      proportion of cells in the sub-G1 phase, normalized the proportion of cells in
      other cell cycle phases. Our results show that the antioxidant activity of
      anthocyanins principally attributed to cyanidin-3-O-glucoside and common to
      blackberry, are effective at inhibiting peroxyl radical induced apoptosis in
      cultured Caco-2 cells.

PMID- 18327701
TI  - Expression of Nrf2 and its downstream gene targets in hibernating 13-lined ground
      squirrels, Spermophilus tridecemlineatus.
AB  - Mammalian hibernation is associated with wide variation in heart rate, blood
      flow, and oxygen delivery to tissues and is used as a model of natural
      ischemia/reperfusion. In non-hibernators, ischemia/reperfusion is typically
      associated with oxidative stress but hibernators seem to deal with potential
      oxidative damage by enhancing antioxidant defenses in an anticipatory manner. The
      present study assesses the role of the Nrf2 transcription factor in the
      regulation of antioxidant defenses during hibernation. Nrf2 mRNA and protein
      expression were enhanced in selected organs of 13-lined ground squirrels,
      Spermophilus tridecemlineatus during hibernation. Furthermore, Nrf2 protein in
      heart was elevated by 1.4-1.5 fold at multiple stages over a torpor-arousal bout
      including during entry, long term torpor, and early arousal. Levels returned to
      euthermic values when squirrels were fully aroused in interbout. Protein levels
      of selected downstream target genes under Nrf2 control were also measured via
      immunoblotting over the torpor-arousal cycle in heart. Cu/Zn superoxide dismutase
      and aflatoxin aldehyde reductase levels increased significantly during entry into
      torpor and then gradually declined falling to control levels or below in fully
      aroused animals. Heme oxygenase-1 also showed the same trend. This suggests a
      role for Nrf2 in regulating the antioxidant defenses needed for hibernation
      success. Heart nrf2 was amplified by PCR and sequenced. The deduced amino acid
      sequence showed high identity with the sequence from other mammals but with
      selected unique substitutions (e.g., proline residues at positions 111 and 230)
      that might be important for conformational stability of the protein at near 0
      degrees C body temperatures in the torpid state.

PMID- 18327702
TI  - The effect of chronic nitric oxide synthases inhibition on regulatory proteins in
      rat hearts.
AB  - The aim of the present study was to characterize the effects of chronic nitric
      oxide synthase (NOS) inhibition on the alterations of regulatory myocardial
      proteins of intracellular signaling pathways (mitogen-activated protein kinase
      (MAPK) and Akt kinase cascades) and matrix metalloproteinases (MMP). Chronic NO
      deficiency (NOD) was induced by NG-nitro-L-arginine methyl ester (L-NAME, 40
      mg/kg/day, 4 weeks). Protein levels and activation of protein kinases were
      determined using specific antibodies, activities of MMP were analyzed by
      zymography in gels containing gelatin as a substrate. The development of NOD was
      associated with decreased activation of endothelial NOS (eNOS) and down
      regulation of protein level of inducible NOS (iNOS). Investigation of kinase
      pathways revealed that the activation of extracellular signal-regulated kinases
      (ERK) and the levels of upstream activators of ERK (aFGF, H-Ras) were decreased
      after L-NAME treatment. Western blot analysis revealed that chronic application
      of L-NAME also decreased the activation of Akt kinase as compared with control
      hearts. Study of MMPs showed that in L-NAME-treated rat hearts activities of
      tissue MMP-2 were decreased. It is concluded that development of NOD resulted in
      inhibition of ERK and Akt kinase pathways and these changes suggest the
      involvement of these cascades in responses of myocardium to NOD. The results also
      point to the possible relationship between ERK and Akt kinase pathways and
      activation of eNOS and/or MMP-2.

PMID- 18327703
TI  - Caffeinated coffee blunts the myocardial protective effects of statins against
      ischemia-reperfusion injury in the rat.
AB  - PURPOSE: We asked whether caffeinated coffee (CC) blunts the infarct size (IS)
      limiting effects of atorvastatin (ATV). BACKGROUND: Adenosine receptor activation
      is essential for mediating the IS-limiting effects of statins. Caffeine is a
      nonspecific adenosine receptor blocker, and thus drinking CC may block the
      myocardial protective effects of statins. METHODS: Rat received 3-day ATV (10
      mg/kg/day) or water by oral gavage once daily. Drinking water was replaced by
      water + sugar (7.5 g/100 ml), CC with sugar, or decaffeinated coffee (DC) with
      sugar. On the 4th day, rats were anesthetized and underwent 30 min of coronary
      artery occlusion and 4 h reperfusion. Area at risk was assessed by blue dye and
      infarct size by TTC. RESULTS: Body weight and area at risk was comparable among
      groups. IS was 25.1 +/- 3.9% of the area at risk in the control group. In rats
      not receiving ATV, CC (25.5 +/- 3.1%) and DC (34.0 +/- 2.8%) did not affect IS.
      IS was significantly reduced by ATV in the water + sugar (11.7 +/- 0.7%, p =
      0.015) and DC (11.5 +/- 1.0%; p < 0.001) groups, but not in the CC group (32.3 +/
      3.0%; p = 0.719). ATV increased myocardial levels of Ser-473 phosphorylated Akt
      in the water + sugar and DC groups, but not in the CC group. CONCLUSIONS: CC, but
      not DC, abrogated the IS-limiting effects of ATV by blocking the adenosine
      receptors and preventing the phosphorylation of Akt. CC did not affect IS in rats
      not receiving ATV.

PMID- 18327704
TI  - Platelet hyperaggregability: impaired responsiveness to nitric oxide ("platelet
      NO resistance") as a therapeutic target.
AB  - Platelet hyperaggregability and associated thrombosis have been documented in a
      number of cardiovascular disease states. While one of the current mainstays of
      anti-thrombotic treatment (i.e. aspirin, clopidogrel, glycoprotein IIb/IIIa
      antagonists) has been directed at reducing platelet activation and aggregation,
      it is apparent that there are limitations to the effectiveness of these
      therapies. Nitric oxide (NO) plays an important role in platelet physiology. The
      ability of NO to regulate cyclic guanosine-3,'5'-monophosphate (cGMP), via
      activation of soluble guanylate cyclase, is the principal mechanism of negative
      control over platelet activity. NO is not only of the endothelial source, it is
      also released from activated platelets, providing a negative feedback. Studies in
      patients with symptomatic ischemia, chronic heart failure, diabetes and various
      risk factors for cardiovascular disease have demonstrated that platelets from
      these subjects exhibit reduced responsiveness to the anti-aggregating efficacy of
      NO: a phenomenon termed "platelet NO resistance". It constitutes an impaired
      physiological response to endogenous NO (endothelium-derived relaxing factor or
      EDRF), and as such may contribute to the increased risk of ischemic events. NO
      resistance also accounts for reduced pharmaco-activity of exogenous NO donors,
      e.g. organic nitrates. Platelet NO resistance results largely from a combination
      of "scavenging" of NO by superoxide anion radical and inactivation of soluble
      guanylate cyclase. NO resistance has both diagnostic and prognostic implications.
      The current review examines the association of platelet NO resistance with
      pathological hyperaggregability and discusses potential therapeutic strategies
      targeting this abnormality.

PMID- 18327705
TI  - Erythropoietin stimulates normal endothelial progenitor cell-mediated endothelial
      turnover, but attributes to neovascularization only in the presence of local
      ischemia.
AB  - PURPOSE: We aimed to evaluate whether ischemia is required for erythropoietin
      (EPO) induced stimulation of endothelial progenitor cells (EPCs) and their
      related effects on endothelial and cardiac function. METHODS: Bone marrow of rats
      was replaced by transgenic cells to allow tracking of EPCs. Ischemic heart
      failure was induced by left coronary artery ligation to induce myocardial
      infarction (MI) and control rats received a sham procedure. Three weeks after
      surgery, rats were randomized to receive EPO (darbepoetin alfa 40 microg/kg per 3
      weeks) or vehicle and were sacrificed 9 weeks after surgery. RESULTS: In all
      treated groups, EPO significantly increased circulating EPCs and their
      incorporation into the endothelium of the ischemic and non-ischemic hearts as
      well as in the control organs; kidney and liver. This was associated with
      significantly improved endothelial function, which was strongly correlated with
      circulating EPCs (R = 0.7, p < 0.01). However, additional EPCs preferentially
      homed to the ischemic MI borderzone (p < 0.01) resulting in specific EPO-induced
      improvement of cardiac microvascularization and performance only in ischemic
      hearts (all p < 0.05). The differential stimulation of neovascularization by EPO
      was associated with increased EPO-receptor and VEGF expression in ischemic hearts
      only. CONCLUSIONS: In general, EPO stimulates normal endothelial progenitor cell
      mediated endothelial turnover, but improves cardiac microvascularization and
      function only in the presence of ischemia.

PMID- 18327706
TI  - A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy
      induced nausea and vomiting in Chinese breast cancer patients receiving
      moderately emetogenic chemotherapy.
AB  - OBJECTIVES: This is a single center, randomized, double-blind placebo-controlled
      study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast
      cancer patients. The primary objective was to compare the efficacy of aprepitant
      based antiemetic regimen and standard antiemetic regimen for the prevention of
      chemotherapy-induced nausea and vomiting (CINV) in patients who received
      moderately emetogenic chemotherapy. The secondary objective was to compare the
      patient-reported quality of life in these two groups of patients. PATIENTS AND
      METHODS: Eligible breast cancer patients were chemotherapy-naive and treated with
      adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600
      mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen
      (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before
      chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd)
      or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and
      dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2
      through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue
      medication were collected with a self-report diary, patients quality of life were
      assessed by self-administered Functional Living Index-Emesis (FLIE). RESULTS: Of
      127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was
      no significant difference in the proportion of patients with reported complete
      response, complete protection, total control, 'no vomiting', 'no significant
      nausea' and 'no nausea'. The requirement of rescue medication appears to be
      lesser in patients treated with the aprepitant-based regimen compared to those
      with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed
      that while there was no difference in the nausea domain and the total score
      between the two groups; however, patients receiving standard antiemetic regimen
      had significantly worse quality of life in the vomiting domain (mean score [SD] =
      23.99 [30.79]) when compared with those who received the aprepitant-based regimen
      (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally
      well tolerated. Patients treated with the aprepitant-based regimen had a
      significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade
      >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of
      chemotherapy (8.1% vs. 27.4%, P = 0.0048). CONCLUSION: The aprepitant regimen
      appears to reduce the requirement of rescue medication when compared with the
      control regimen for prevention of CINV in patients receiving both an
      anthracycline and cyclophosphamide, and is associated with a better quality of
      life during adjuvant AC chemotherapy.

PMID- 18327707
TI  - Tumor-specific RNAi targeting eIF4E suppresses tumor growth, induces apoptosis
      and enhances cisplatin cytotoxicity in human breast carcinoma cells.
AB  - BACKGROUND: Eukaryotic initiation factor eIF4E, an important regulator of
      translation, plays a crucial role in the malignant transformation, progression
      and chemoresistance of many human solid tumors. The overexpression of this gene
      has been found in a variety of human malignancies including breast carcinoma. In
      the present study, we attempted to explore the possibility of eIF4E as a
      therapeutic target for the treatment of human breast carcinoma using breast
      carcinoma cell line (MCF-7). MATERIALS AND METHODS: The survivin promoter-driven
      eIF4E-shRNA vector was constructed on the basis of pSUPER.retro vector. Then, we
      established stably transfected MCF-7 and MCF210 (normal human mammary epithelial
      cell) cells expressing eIF4E-shRNAs or control-shRNAs. Firstly, the changes of
      eIF4E expression were detected by RT-PCR and Western blot assays. Next, the
      optimal shRNA vector (eIF4E-shRNA2) was selected to knock down eIF4E expression
      and investigate the effect of eIF4E-shRNA on eIF4E-regulated gene expression and
      cell proliferation both in vitro and in vivo. Followingly, the changes of cell
      cycle and apoptosis in the stably transfectants (MCF-7) were detected by flow
      cytometry and TUNEL methods, while we also explored possible apoptosis pathways.
      Finally, we investigated the effect of shRNA targeting eIF4E on the
      chemosensitivity of breast carcinoma cells to cisplatin in vitro and in vivo.
      RESULTS: Two survivin promoter-driven eIF4E-shRNA vectors were successfully
      constructed. eIF4E-shRNA2 but not eIF4E-shRNA1 efficiently downregulated the
      levels of eIF4E expression in the stably transfected MCF-7-s2 cells but not in
      the stably transfected MCF210-s2 cells, while MCF-7-s2 showed obvious
      proliferation suppression but MCF210-s2 did not. The downregulation of eIF4E
      expression significantly reduced the levels of VEGF, FGF-2 and cyclinD1
      expression, suppressed cell growth, induced cell cycle arrest in G(0)/G(1) phase
      and subsequent apoptosis by activating caspase 3 in MCF-7 cells. The results of
      FCM and TUNEL staining assays indicated that the classic apoptosis characters of
      the MCF-7 cells stably expressing eIF4E-shRNA2 manifested an apoptosis rate of
      18.3%, significantly higher than those in the control groups (P < 0.05).
      Moreover, we found that downregulation of c-IAP1, c-IAP2 and c-Myc but not Bcl-2
      family proteins were involved in the apoptosis induced by eIF4E-shRNA2. In
      tumorigenicity assay, xenograft tumors developed from MCF-7-s2 cells in mice
      showed a significant slowdown in the growth speed and formation rate compared
      with control groups. Furthermore, we also testified that eIF4E-shRNA could
      synergistically enhance the cytotoxicity effects of cisplatin to MCF-7 cells both
      in vitro and in vivo. CONCLUSION: Survivin promoter-driven RNA interference
      system could efficiently and specifically downregulate eIF4E expression in human
      breast carcinoma cells but not in normal human mammary epithelial cell cells.
      Thus, eIF4E might play an important role in chemosensitivity to cisplatin, and
      survivin promoter-driven RNAi targeting eIF4E can be used as adjuvant therapy for
      human breast carcinomas with tumor specificity and high efficacy.

PMID- 18327708
TI  - Ogataea nitratoaversa sp. nov., a methylotrophic yeast species from temperate
      forest habitats.
AB  - Three methanol-assimilating, nitrate-negative yeast strains representing a
      hitherto undescribed species, were isolated from leaf and rotten wood samples
      collected in temperate forests in Hungary. Analysis of the D1/D2 large subunit
      ribosomal RNA gene sequences placed the strains in the Ogataea clade. The three
      strains share identical D1/D2 and ITS sequences and significantly differ from the
      genetically most closely related species, Pichia pilisensis. Five substitutions
      in D1/D2 and more than 10% difference in the ITS regions were detected. A novel
      yeast species, Ogataea nitratoaversa, is proposed to accommodate these isolates.
      The type culture is NCAIM Y.01837(T) (CBS 10,796, NRRL Y-48,449). As the current
      description of the genus does not allow the inclusion of nitrate negative
      species, the emendation of the diagnosis of the genus Ogataea Yamada, Maeda and
      Mikata is proposed.

PMID- 18327709
TI  - The potential for translocation of marine species via small-scale disruptions to
      antifouling surfaces.
AB  - Vessel hull fouling is a major vector for the translocation of nonindigenous
      species (NIS). Antifouling (AF) paints are the primary method for preventing the
      establishment and translocation of fouling species. However, factors such as
      paint age, condition and method of application can all reduce the effectiveness
      of these coatings. Areas of hull that escape AF treatment (through limited
      application or damage) constitute key areas that may be expected to receive high
      levels of fouling. The investigation focused on whether small-scale (mm(2) to
      cm(2)) areas of unprotected surface or experimental 'scrapes' provided sufficient
      area for the formation of fouling assemblages within otherwise undamaged AF
      surfaces. Recruitment of fouling taxa such as algae, spirorbids and hydroids was
      recorded on scrapes as narrow as 0.5 cm wide. The abundance and species richness
      of fouling assemblages developing on scrapes > or =1 cm often equalled or
      surpassed levels observed in reference assemblages totally unprotected by AF
      coatings. Experiments were conducted at three sites within the highly protected
      and isolated marine park surrounding Lady Elliott Island at the southernmost tip
      of the Great Barrier Reef, Australia. Several NIS were recorded on scrapes of AF
      coated surfaces at this location, with 1-cm scrapes showing the greatest species
      richness and abundance of NIS relative to all other treatments (including
      controls) at two of the three sites investigated. Slight disruptions to newly
      antifouled surfaces may be all that is necessary for the establishment of fouling
      organisms and the translocation of a wide range of invasive taxa to otherwise
      highly protected marine areas.

PMID- 18327711
TI  - Protein and DNA reactions stimulated by electromagnetic fields.
AB  - The stimulation of protein and DNA by electromagnetic fields (EMF) has been
      problematic because the fields do not appear to have sufficient energy to
      directly affect such large molecules. Studies with electric and magnetic fields
      in the extremely low-frequency range have shown that weak fields can cause charge
      movement. It has also been known for some time that redistribution of charges in
      large molecules can trigger conformational changes that are driven by large
      hydration energies. This review considers examples of direct effects of electric
      and magnetic fields on charge transfer, and structural changes driven by such
      changes. Conformational changes that arise from alterations in charge
      distribution play a key role in membrane transport proteins, including ion
      channels, and probably account for DNA stimulation to initiate protein synthesis.
      It appears likely that weak EMF can control and amplify biological processes
      through their effects on charge distribution.

PMID- 18327712
TI  - Effects of static and low-frequency alternating magnetic fields on the ionic
      electrolytic currents of glutamic acid aqueous solutions.
AB  - A current peak has been observed and measured in ionic electrolytic current of a
      glutamic acid aqueous solution, placed in a static magnetic field of flux density
      of 40 microT, with a superimposed low-frequency alternating magnetic field of
      flux density of 40 nT. The peak occurs at the frequency of the cyclotronic
      resonance of the molecular mass of a single charged glutamic acid ion, placed in
      a magnetic flux density equal to that of the static field. The amplitude of the
      current peak is about 30% of the background electrolytic current. Qualitative
      considerations and a listing of unsolved problems related to the phenomenology
      are given. The result is the first contribution to the study we have undertaken
      on the effects of low-frequency alternating electromagnetic fields on the ionic
      current of amino acid aqueous solutions which are the basic structural units of
      the proteins.

PMID- 18327713
TI  - Low-energy electromagnetic fields promote proliferation of vascular smooth muscle
      cells.
AB  - The rationale was to investigate the effects of low-energy electromagnetic fields
      (EMF) on the proliferation of bovine coronary and murine aortic smooth muscle
      cells (SMC). EMF were applied to SMC at field frequencies of 25, 50, or 100 Hz,
      and exposure time was set to 5, 15, or 30 minutes. Significant increases in SMC
      counts compared with sham exposed controls were found for all EMF-frequencies
      tested. The effect was most pronounced for 50 Hz fields with maximum increases of
      1.2-fold over controls. Sequential double exposure of mouse aortic SMC to 50 Hz
      fields revealed significantly enhanced cell proliferation by 1.2 fold compared
      with single exposure (p < 0.05). Experiments performed on bovine SMC also
      revealed significant increases in cell proliferation. The results demonstrate
      that EMF are capable of significantly enhancing the proliferation of vascular
      SMC. These results rise the question whether EMF would qualify as supportive
      means to angio-/arteriogenic approaches.

PMID- 18327714
TI  - Mechanobiology of MG63 osteoblast-like cells adaptation to static magnetic
      forces.
AB  - The aim of this study was to explore the biophysical effects of static magnetic
      field on osteoblastic cells. MG63 cells were exposed to 0.25 and 0.4-T static
      magnetic fields (SMF). The cell cycle effects were tested by flow cytometry. The
      differentiation of the cells was assessed by detecting the changes in
      prostaglandin E2, osteocalcin, and extracellular matrix expression. Membrane
      fluidity was used to evaluate the alterations in the biophysical properties of
      cellular membranes after the SMF simulations. Our results show that SMF exposure
      increases prostaglandin E2 level and extracellular matrix express in MG63 cells.
      On the other hand, MG63 cells exposed to 0.4-T SMF exhibited a significant
      decrease in membrane fluidity at 8 h. Based on these findings, it appears
      reasonable to suggest that SMF affect osteoblastic maturation by increasing
      membrane rigidity and then inducing differentiation pathway.

PMID- 18327715
TI  - Whole-body exposure of radiation emitted from 900 MHz mobile phones does not seem
      to affect the levels of anti-apoptotic bcl-2 protein.
AB  - The purpose of the present study was to investigate the anti-apoptotic bcl-2
      protein in rat brain and testes after whole-body exposure to radiation emitted
      from 900 MHz cellular phones. Two groups (sham and experimental) of Sprague
      Dawley rats of eight rats each were used in the study. Exposure began
      approximately 10 min after transferring into the exposure cages, a period of time
      when rats settled down to a prone position and selected a fixed location inside
      the cage spontaneously. For the experimental group, the phones were in the speech
      condition for 20 min per day for 1 month. The same procedure was applied to the
      sham group rats, but the phones were turned off. Immunohistochemical staining of
      bcl-2 was performed according to the standardized avidin-biotin complex method.
      The results of this study showed that 20 min of the radiation emitted from 900
      MHz cellular phones did not alter anti-apoptotic bcl-2 protein in the brain and
      testes of rats. We speculate that bcl-2 may not be involved in the effects of
      radiation on the brain and testes of rats.

PMID- 18327716
TI  - Development and validation of reverberation-chamber type whole-body exposure
      system for mobile-phone frequency.
AB  - We developed whole-body exposure systems for in-vivo study at cellular (848.5
      MHz) and Personal Communication System (PCS, 1,762.5 MHz) frequency, utilizing
      reverberation chamber. The field uniformities in the test area of the designed
      chambers were verified by simulation and measurement. In the whole-body exposure
      environment, Specific Absorption Rate (SAR) distributions inside of mice were
      calculated using Finite Difference Time Domain (FDTD) simulation. Key results are
      presented in this article.

PMID- 18327717
TI  - Point and interval estimation of primary and secondary parameters in a two-stage
      adaptive clinical trial.
AB  - Investigated in this paper is the point estimation and confidence intervals of
      the treatment efficacy parameter and related secondary parameters in a two-stage
      adaptive trial. Based on the minimal sufficient statistics, several alternative
      estimators to the sample averages are proposed to reduce the bias and to improve
      the precision of estimation. Confidence intervals are constructed using
      Woodroofe's pivot method. Numerical studies are conducted to evaluate the bias
      and mean squared error of the estimators and the coverage probability of the
      confidence intervals.

PMID- 18327718
TI  - A Bayesian approach to utilizing prior data in new drug development.
AB  - In this paper we propose a Bayesian method to combine safety data collected from
      two separate drug development programs using the same active drug substance but
      for different indications, formulations, or patient populations. The objective of
      combining the data across the programs is to better define the level of safety
      risk associated with the new indication or target population. There may be
      adverse events (AEs) observed in the new program that represent new safety
      signals. Our method is to explore the AEs using data from both development
      programs. Our approach utilizes data collected previously to assist in analyzing
      safety data from the new program. It is assumed that the frequency of a certain
      AE follows a distribution with a parameter that characterizes the safety risk
      level. The parameter is assumed to follow a distribution function. In the
      Bayesian framework, this distribution function is called a prior distribution in
      the absence of data and posterior distribution when updated by real data. The key
      concept behind our method is to use data from the previous program to construct a
      posterior distribution that will in turn serve as a prior distribution for the
      new program. The construction of this updated prior down weights data from the
      previous program to emphasize the new program and thus avoids simple pooling of
      the data across programs. Such "soft use" of previous information minimizes the
      potential for undue influence of previous data on the analysis. Data from the new
      program are used to update the prior distribution and compute the posterior
      distribution for the new program. Key statistics are then calculated from the
      posterior distribution to quantify the risk level for the new program. We have
      tested the proposed approach using data from a real Phase 2 study that was
      conducted as part of a clinical development program for a new indication of an
      approved drug. The results indicate that the estimated risk level was affected
      both by the observed event rates and the extents of exposure across the two
      development programs. This approach appropriately characterizes the safety
      profile across the two development programs and properly contextualizes new
      safety signals from the new program.

PMID- 18327719
TI  - ICI: a new approach to explore between-cluster relationships with applications to
      gene expression data.
AB  - Clustering methods are typically used to group objects with similar patterns into
      one of k sets. In the case of gene expression data, genes clustered into the same
      set tend to have similar expression profiles. However, clustering techniques lack
      a mechanism to quantify the between-cluster relationship. We propose a method
      called ICI (Inter-Cluster Investigator) to ascertain the between-cluster and
      between-gene relationships and establish the amount of co-regulation between
      clustered sets of genes. This will yield an alternative way of characterizing the
      between-gene relationship that builds upon the existing structure obtained from
      clustering. A procedure is proposed to allow the identification of negatively and
      positively correlated sets of genes, which may indicate repression or regulation
      in gene expression data. It is illustrated with the analysis of yeast cell-cycle
      data.

PMID- 18327720
TI  - Bayesian hierarchical modeling of receptor occupancy in PET trials.
AB  - Receptor occupancy (RO) PET is a non-invasive way to determine drug on target.
      Given the complexity of procedures, long acquisition times, and high cost, ligand
      displacement imaging trials often have a limited size and produce sparse RO
      results over the time course of the blocking drug. To take the best advantage of
      the available data, we propose a Bayesian hierarchical model to analyze RO as a
      function of the displacing drug. The model has three components: the first
      estimates RO using brain regional time-radioactivity concentrations, the second
      shapes the pharmacokinetic profile of the blocking drug, and the last relates PK
      to RO. Compared to standard 2-steps RO estimation methods, our Bayesian approach
      quantifies the variability of the individual RO measures. The model has also
      useful prediction capabilities: to quantify brain RO for dosage regimens of the
      drug that were not tested in the experiment. This permits the optimal dose
      selection of neuroscience drugs at a limited cost. We illustrate the method in
      the prediction of RO after multiple dosing from a single-dose trial.

PMID- 18327721
TI  - Estimation of the risk difference under a noncompliance randomized clinical trial
      with missing outcomes.
AB  - In a randomized clinical trial (RCT), we often come across the situations in
      which there are patients who do not comply with their assigned treatments or
      whose outcomes are missing due to their refusal or loss to follow-up. Because
      noncompliance and missing outcomes do not generally occur completely at random,
      analyzing data as treated or excluding patients with missing outcomes from our
      analysis can produce a biased estimate of a treatment effect. In this paper, we
      consider estimation of the risk difference (RD) in the presence of both
      noncompliance and missing outcomes under a RCT. On the basis of a constant risk
      additive model proposed elsewhere, we derive the maximum likelihood estimator
      (MLE) and develop three asymptotic interval estimators in closed form for the RD
      when we have outcome missing at random. We apply Monte Carlo simulation to
      evaluate and compare the performance of these estimators in a variety of
      situations. We note that all interval estimators developed here can perform well
      with respect to the coverage probability in all the situations considered here.
      We find that the interval estimator using tanh-1(x) transformation is generally
      more precise than the other two estimators with respect to the average length.
      Finally, we use the data taken from a randomized trial studying the association
      between flu vaccine and the risk of flu-related hospitalization to illustrate the
      practical use of these interval estimators.

PMID- 18327722
TI  - Joint one-sided and two-sided simultaneous confidence intervals.
AB  - For the analysis of multiarmed clinical trials often a set consisting of a
      mixture of one- and two-sided tests can be preferred over a set of common two
      sided hypotheses settings. Here we show the straightforward application of
      existing multiple comparison procedures for the difference and ratio of normally
      distributed means to complex trial designs, involving one and two test
      directions. The proposed contrast tests provide a more flexible framework than
      the existing methods at nearly similar power. An application is illustrated for
      an example with multiple treatment doses and two active controls; statistical
      software codes are included for R and SAS System.

PMID- 18327723
TI  - A four-parameter logistic model for estimating titers of functional multiplexed
      pneumococcal opsonophagocytic killing assay.
AB  - In vitro opsonophagocytosis killing assay (OPA) is widely accepted to quantitate
      Streptococcus pneumococcal antibodies to serotype-specific pneumococcal capsular
      polysaccharide (PS). A titer estimation method is needed for large scale data
      generated by OPA, and it is one component of OPA standardization. In order to
      improve the reliability of OPA results, we developed a nonlinear fitting method
      using the Levenberg-Marquardt algorithm with an option of a robust procedure to
      estimate titers of OPA data. Performance of the proposed method was evaluated by
      comparing precision and accuracy of titer estimation with traditional methods
      used in the literature by analyzing real experimental data sets. Goodness-of-fit
      to experimental data for the two model-based methods was also assessed. We
      conclude that the four-parameter logistic model is an alternative choice for
      titer estimation of OPA data. Computer software using the statistical language R
      and Microsoft Excel was developed to implement our calculation algorithm for OPA
      data.

PMID- 18327724
TI  - Information theory-based surrogate marker evaluation from several randomized
      clinical trials with binary endpoints, using SAS.
AB  - One of the paradigms for surrogate marker evaluation in clinical trials is based
      on employing data from several clinical trials: the meta-analytic approach. It
      was originally developed for continuous outcomes by means of the linear mixed
      model, but other situations are of interest. One such situation is when both
      outcomes are binary. Although joint models have been proposed for this setting,
      they are cumbersome in the sense of computationally complex and of producing
      validation measures that are, unlike in the Gaussian case, not of an R(2) type
      (Burzykowski et al., 2005). A way to put these problems to rest is by employing
      information theory, already applied in the continuous case (Alonso and
      Molenberghs, 2007). In this paper, the information-theoretic approach is applied
      to the case of binary surrogate and true endpoints. Its use is illustrated using
      a case study in acute migraine and its performance, relative to existing methods,
      assessed by means of a simulation study. Because the usefulness of a method
      critically depends, among others, on the availability of software, a SAS
      implementation accompanies the methodological work.

PMID- 18327725
TI  - Incorporating correlation in interindividual variability for the optimal design
      of multiresponse pharmacokinetic experiments.
AB  - This paper presents a method for optimal design of multiresponse population
      pharmacokinetic experiments taking into account correlations between
      interindividual variances. Expressions for the population Fisher information
      matrix have been defined for uniresponse and multiresponse pharmacokinetic
      experiments. A major assumption often made is that the variance-covariance matrix
      of the interindividual variance components has only diagonal elements so that
      whenever intersubject covariance elements are present, they are ignored during
      the design of the experiment. Recently expressions that accounted for these off
      diagonal elements were developed for uniresponse population pharmacokinetic
      experiments. The work presented here extends these expressions to multiresponse
      population pharmacokinetic experiments. These were applied to a population
      pharmacokinetic model, a population pharmacokinetic-pharmacodynamic model, and a
      parent-metabolite pharmacokinetic model example. The results obtained showed that
      optimal designs are different with diagonal omega matrix and full omega matrix
      and ignoring the off diagonal elements can lead to a design that produces more
      biased and less precise parameter estimates compared to a design that includes
      the off diagonal elements. The results also showed correlation between residual
      components of the responses has an effect on the optimal design.

PMID- 18327726
TI  - Sample size for comparing correlated concordance rates.
AB  - We consider collecting the measurements of a gold standard and two methods with
      error from each site of subjects. We propose an asymptotic test statistic to
      compare the concordance rates of two methods with the gold standard and a closed
      form sample size formula. Through simulations, we show that the test statistic
      accurately controls the type I error in small sample sizes, and the sample size
      formula accurately maintains the power in various settings. The proposed test
      statistic and the sample size formula can be easily modified for other indices
      for agreement such as sensitivity and specificity. A real eye study is taken as
      an example.

PMID- 18327727
TI  - What we want versus what we can get: a closer look at failure time endpoints for
      cardiovascular studies.
AB  - In this article, we review the use of all-cause mortality and the composite
      endpoint as the primary endpoint and propose a recurrent composite endpoint as an
      alternative primary endpoint. Some general suggestions to trialists and
      practitioners are provided. In summary, the use of the composite endpoint is an
      issue that needs clarification.

PMID- 18327728
TI  - Assessing learning effects and nonrandom dropout in a contraceptive device trial.
AB  - When there is a new device involved in a randomized trial, participants in the
      new device group might need more time to become skilled at using the new device
      than those who are in the control group. In addition, participants who are not
      used to the new device might drop out from the study at a different rate than
      participants in the control group. Such learning effects and possible nonrandom
      dropout can substantially influence the evaluation of treatment effects. Without
      considering these factors, the conclusion of the main study result is vulnerable
      to potential bias. In this paper we propose a transition model under a Markov
      process to assess the effects of learning and nonrandom dropout in a randomized
      control device trial. The transition probabilities of the proposed model can be
      obtained by maximum likelihood approaches, and then fit by weighted local
      regressions to describe patterns of learning and participant dropout. A
      generalized estimating equation approach is applied to evaluate the impact of
      prognostic factors on those patterns. We use data from a randomized contraceptive
      device trial to illustrate the usefulness of the proposed method. The potential
      impact of learning effects and nonrandom dropout on the primary study objective
      is discussed.

PMID- 18327734
TI  - [Vaccination and vaccinology in the world of evidence based medicine].

PMID- 18327735
TI  - [The importance of the second generation adjuvanted systems in "new" vaccines].
AB  - The so called "first generation adjuvants" have been based on aluminium salts and
      they were added to vaccines composition to enhance immune response to vaccine
      antigen. Formerly produced vaccines contained inactivated or attenuated
      microorganisms, which were able to promote all necessary signals for high immune
      response. Nevertheless there was also produced immune response and also adverse
      events to antigens, which were not necessary for protection. Vaccinology has been
      further developed with possibility to produce recombinant and subunit antigens,
      which were needed for protection against infection. It was necessary to intensify
      targeted immune response against recombinant antigen, for fast and long term
      protection. Such need stimulated research for development of "adjuvanted systems
      of the second generation", which were tailored to particular antigen. Former
      adjuvants were based on stimulation of adaptive immunity. Contrary the first the
      second generation of adjuvanted systems is based on Pathogen-Associated Molecular
      Patterns (PAMP). By binding to Toll-like receptors (mostly TLR-4) as a part of
      innate immunity, they are able to influence adaptive immunity including humoral
      and also cellular arm of immune system. Licensed vaccines with second generation
      of adjuvant systems are Cervarix and Fendrix vaccines and in development are
      vaccines against malaria and genital herpes. Also for pre-pandemic vaccines is
      used new generation of adjuvanted systems.

PMID- 18327736
TI  - [Ten year's experience with combined hepatitis A and B vaccine].
AB  - Hepatitis A and B are still a serious global public health problem. Monovalent
      vaccines against hepatitis A and B have been available on the European but also
      on the Czech market for long time. Since 1997 different formulations and
      immunization schedules of the first combined vaccine against both diseases have
      been gradually introduced into clinical practice. Twinrix Adult (with
      conventional and accelerated schedules), and Twinrix Paediatric are available for
      all patients in Europe and also in USA. AmBirix as a two scheduled vaccine for
      age from 1-15years is licensed in Europe. These vaccines offer fewer injections
      for satisfactory protection against hepatitis A and B and an excellent safety and
      reactogenicity profile in comparison to monovalent vaccines. This review is
      dominantly focused on immunogenicity, safety and reactogenicity data of the
      vaccine, which are available now for more than 10 years.

PMID- 18327737
TI  - [A study of antibiotic treatment of upper respiratory infections in primary
      care].
AB  - OBJECTIVE: To assess the antibiotic therapy of and approach to treating
      pharyngitis/tonsillopharyngitis in primary care physicians, including the trends
      and rationality. METHODS: In April 2005, a multicentre study was carried out as a
      sequel to a similar study performed in 1998. The two studies monitored how
      primary care physicians treated patients subsequently hospitalized in Czech
      departments of infectious diseases with the diagnosis of acute upper respiratory
      infection. Patients' data were provided by physicians from the departments of
      infectious diseases in standard questionnaires and processed by employees of a
      Prague department of infectious diseases. RESULTS: In 1998, 14 departments of
      infectious diseases participated in the study and 241 valid questionnaires were
      obtained from them. The 2005 study comprised 21 departments and 324 valid
      questionnaires. According to their final diagnosis, patients were divided into
      four groups: infectious mononucleosis, viral infection, bacterial infection and
      infectious mononucleosis with bacterial superinfection. The study included only
      patients initially treated and/or examined by primary care physicians and later
      referred to a hospital; patients directly referred to a hospital were not
      enrolled. The numbers of assessable cases were 188 in 1998 and 199 in 2005.
      Primary care physicians' approach was evaluated according to defined criteria.
      Respiratory infections were treated correctly in 63 cases (34 %) in 1998 and in
      84 cases (42 %) in 2005. Incorrect treatment was found in 66 cases (35 %) in 1998
      and in 60 cases (30 %) in 2005. The most common forms of incorrect approach were
      as follows: antibiotics prescribed for viral infections, aminopenicillin
      prescribed for infectious mononucleosis and unwarranted administration of
      protected aminopenicillins in upper respiratory infections. In all three
      categories, improvements in prescription were noted in 2005 as compared with
      1998, yet the differences were not statistically significant. In 2005, outpatient
      CRP tests for evaluating the aetiology of pharyngitis/tonsillopharyngitis were
      significantly more frequent. CONCLUSIONS: When comparing results of the 1998 and
      2005 studies, certain improvements in prescription of antibiotics for treating
      respiratory infections in primary care were noted. Also positive is the
      outpatient use of CRP tests. On the other hand, there still are numerous cases
      when antibiotics are prescribed irrationally, without prior examination, and
      their choice is not in accordance with guidelines. This study provides an option
      for close monitoring of prescription by primary care physicians. Specialists are
      capable of objective evaluation of primary care physicians' work and
      specification of errors. These may be focused on and dealt with when education
      programmes for primary care physicians are developing.

PMID- 18327738
TI  - [The importance of pneumococcal vaccination - a clinician's view].
AB  - Reliable epidemiological surveillance of pneumococcal diseases is crucial for
      rational decisions concerning the introduction of vaccination strategies. In
      countries with such close surveillance (e.g. in the USA or Belgium), the acquired
      epidemiological data warranted universal vaccination. Pneumococci cause short
      time asymptomatic colonization of the human nasopharynx. If defense mechanisms
      fail, pneumococci may penetrate to previously sterile areas and cause local
      infections in the upper airways. In case they reach the bloodstream, invasive
      infections occur that threaten health or even lives of both children and adults.
      Therapeutic options are limited due to increasing resistance of pneumococci to
      antibiotics. Possible prevention of particularly invasive infections is
      vaccination of adults with a 23-valent polysaccharide vaccine and children over
      two months of age with a polyvalent conjugate vaccine. Therefore, the WHO
      recommends that the pneumococcal conjugate vaccine is included in national
      vaccination programmes as soon as possible.

PMID- 18327739
TI  - [Continuing professional development: a medical requirement].

PMID- 18327740
TI  - [A descriptive study of neurocysticercosis in a tertiary care hospital].
AB  - INTRODUCTION: Neurocysticercosis is the most frequent parasitic disease affecting
      the central nervous system. It is a disease that is endemic to certain countries
      in South America. The phenomenon of immigration, however, has increased its
      prevalence in developed regions due to the arrival of immigrants from endemic
      areas. AIM: To present the clinical and demographic characteristics of the cases
      of neurocysticercosis attended in a tertiary care hospital in the city of Murcia.
      PATIENTS AND METHODS: We conducted a descriptive, retrospective study by
      reviewing the medical records of patients with a hospital diagnosis of
      neurocysticercosis over a nine-year period (1997-2005). Demographic and clinical
      data on these patients were collected. RESULTS: Twenty-three patients (three
      under 12 years of age) were found. Mean age: 29.6 years. Countries of origin:
      Ecuador and Bolivia. The most frequently observed clinical manifestations were:
      epileptic seizures (73.9%), headache (39.1%) and neurological focus (26.1%).
      Albendazole was employed in 91.3% of cases and corticoids in 73.9%. The most
      frequently used drug in patients who received antiepileptic therapy was
      phenytoin. Four patients required surgical treatment. During the follow-up
      period, 52.8% of the patients were asymptomatic. CONCLUSIONS: Neurocysticercosis
      is a disease that is becoming increasingly more prevalent in Spain and we should
      suspect its presence in patients from endemic areas who visit because of clinical
      symptoms involving the central nervous system.

PMID- 18327741
TI  - [Pathological neocortical findings in patients with medication-resistant medial
      temporal lobe epilepsy submitted to surgery].
AB  - INTRODUCTION: The dual pathology consisting of hippocampal sclerosis plus focal
      cortical dysplasia (FCD) is often reported in patients with medication-resistant
      medial temporal lobe epilepsy (MTLE). AIMS: To determine the histopathological
      changes that take place in the neocortex of patients with medication-resistant
      MTLE submitted to surgery and to evaluate the relation between the
      histopathological changes, pathological background and the clinical course of
      patients who had received surgical treatment. MATERIALS AND METHODS: Tissue
      obtained by en bloc resection from the neocortex of 18 patients with MTLE
      refractory to medical treatment was processed histologically and a tailored
      temporal lobectomy was performed with electrocorticography. RESULTS: Dual
      pathology was diagnosed in 13 patients (72.2%). Imaging studies confirmed the
      existence of mesial sclerosis of the temporal in 100% of cases and there was no
      evidence of neocortical lesions. Histologically, 46.15% and 38.46% of the
      patients were diagnosed as belonging to FCD type 1a and FCD type 1b,
      respectively. Only one patient presented FCD type 2a. A statistically significant
      relation was found between the presence of dual pathology and the existence of an
      early precipitating injury (p = 0.04). One year after surgery, 72.7% (8/11)
      patients with dual pathology were classified as belonging to Engel class I.
      CONCLUSIONS: In patients with MTLE there are microscopic FCD-type alterations in
      the neocortex. There is an association between these alterations and the
      existence of an initial precipitating injury. Complete resection of the
      epileptogenic area, which is guaranteed by the lobectomy tailored by
      electrocorticography, allows patients to enjoy a favourable post-surgical
      progression one year after surgery.

PMID- 18327742
TI  - [Thalamic dementia secondary to acute bilateral paramedian thalamic infarcts
      after occlusion of the artery of Percheron].
AB  - INTRODUCTION: The anterior and medial part of the thalamus is the responsible of
      multiples cognitive functions through the thalamus-cortical connections. A
      bilateral thalamic infarction can cause a secondary dementia and these are
      related to a thalamocortical deafferentation with a partial recovery. We report a
      case of sudden onset dementia caused by bilateral thalamus lesions. CASE REPORT:
      A 42 smoker male, that suddenly had an acute confusional syndrome with altered
      language, bradypsychia, right hemiparesis and right hemisensory loss. Cranial
      magnetic resonance imaging showed a bilateral thalamic stroke probably due to a
      variant talamus irrigation (artery of Percheron type 2). From this date, in three
      months, the patient had attention deficit, impairment of memory retention,
      apathy, initiative deficit, depressive syndrome and mood changes. All these
      symptoms improving partially in the following six months. CONCLUSIONS: The
      thalamic stroke can cause a thalamic dementia, commonly bilateral and preferable
      located in the anterior and medial nuclei. In our case, cranial SPECT showed
      frontal hypocaptation for diaschisis phenomenon.

PMID- 18327743
TI  - [Conditioned preferences induced by sex and drugs: a comparison of the neural
      bases].
AB  - AIM: To compare the behavioral and neural bases of conditioned preferences
      induced by drugs and sex in animal models. DEVELOPMENT: Sex- and drug-induced
      preferences have certain commonalities. For example, sex and drug reward can
      induce the development of new preferences, leading to the idea that the partner
      preferences that develop after sexual encounters and drug consumption are, in
      part, consequences of classical conditioning. Both phenomena depend on the
      activity of mesolimbic areas, and neurotransmitters such as dopamine, opioids and
      oxytocin. Agonists for these neurotransmitters facilitate conditioned preferences
      in the absence of sex and drug reward, whereas antagonists disrupt them even
      after sex or drug consumption. CONCLUSIONS: This review adds evidence to the idea
      that conditioned preferences induced by drugs use similar neural systems as those
      that evolved to sense and learn about natural rewards like sex.

PMID- 18327744
TI  - [Cognitive-motor interactions: the role of motor representation].
AB  - INTRODUCTION: In the last decade, studies in cognitive neuroscience have
      considerably furthered our knowledge about the interactions between cognition and
      action. In particular, motor representation is seen to be one of the cognitive
      processes involved in the production of movement. This motor representation was
      deduced from comparisons between cognitive (e.g. motor imagination) and motor
      processes (e.g. motor performance). Yet, the interactions between this
      representation and other cognitive-motor processes such as motor planning eclipse
      the importance of the function of motor representation in action. In addition,
      this situation often gives rise to confusion when it comes to interpreting the
      function of motor representation. Consequently, the exact role it plays in
      producing movement is not very clear. DEVELOPMENT: In order to clarify this role,
      we analyse imagination, preparation, planning, motor performance, affordances and
      automated movements. At the same time, we also propose a hypothetical scheme of
      the functioning of motor representation during the execution of a movement and an
      action. CONCLUSIONS: Motor representation can be considered as an active
      component in certain cognitive-motor processes that enables motor response to be
      updated online, as well as allowing the optimisation and acquisition of new motor
      skills.

PMID- 18327745
TI  - [Adult learning, professional autonomy and individual commitment].
AB  - DEVELOPMENT: The concept of 'andragogy' is the basis of the adult education which
      is different from pedagogy in several aspects, particularly in the autonomy of
      the adult learner in choosing the educational programmes and the methodologies
      and sites in where learning occurs. This happens very often in the worksite. The
      professionals have to learn permanently during their active lives in order to
      maintain their competence updated. In this sense, continuing education correlates
      with continuing professional development, which is an attempt to enlarge the
      traditional domains of continuing education. Continuing education must be clearly
      differentiated from formal education, which is a requirement for granting
      professional degrees or titles. Very often it arises from the changing health
      needs and for this reason is necessary to avoid the institutionalization of
      continuing education programmes. CONCLUSION: Professional associations should be
      actively involved in providing and accrediting continuing education-continuing
      professional development programmes, because this involvement is an essential
      component of the professionals' self-regulation in the context of the current
      medical professionalism ideology.

PMID- 18327746
TI  - [Analysis of the behaviour of Guillain-Barre syndrome. Agreements and
      discrepancies].
AB  - INTRODUCTION: Despite the advances made to explain the aetiopathogenesis of
      Guillain-Barre syndrome (GBS), there are a number of conflicting opinions as
      regards its behaviour. AIM. To analyse the controversial issues regarding the
      clinical-epidemiological behaviour of GBS. DEVELOPMENT: We highlight the variety
      of opinions concerning the characterisation of GBS. We also analyse the possible
      causes of the regularities and irregularities in its behaviour. We believe the
      irregularities may be determined by environmental and genetic factors. Among the
      environmental factors, we consider the most important to be the variability of
      the previous phenomenon. There are genetically determined factors that can make
      some individuals more susceptible and others more vulnerable to developing GBS.
      We discuss the reasons that, in our view, hinder epidemiological processing using
      traditional statistical methods. CONCLUSIONS: GBS is a condition that behaves in
      a very particular manner. It displays very interesting regularities and
      irregularities that may be determined by the influence of environmental and
      genetic factors. The low incidence of the condition is a hindrance when it comes
      to processing epidemiological data with traditional statistical methods, which
      are ineffective for characterising the behaviour of the syndrome. Tools therefore
      need to be developed that make it possible to better study the dynamics of the
      syndrome and help to explain the mechanisms involved in its causality.

PMID- 18327747
TI  - [Pneumocephalus following spinal anaesthetic].

PMID- 18327749
TI  - [Harlequin syndrome secondary to thoracic chondrosarcoma].

PMID- 18327750
TI  - [Acute dystonia following paroxetine withdrawal].

PMID- 18327751
TI  - [Cerebral infarction produced by embolised material from an intracardiac foreign
      body].

PMID- 18327752
TI  - [HaNDL syndrome and Hashimoto's encephalopathy].

PMID- 18327753
TI  - [Frontal absences and 'pseudo-absences'].

PMID- 18327755
TI  - Rapid cooling experiments and use of an anionic nuclear probe to sense the spin
      transition of the 1D coordination polymers [Fe(NH2trz)3]SnF6n x H2O (NH2trz=4
      amino-1,2,4-triazole).
AB  - [Fe(NH2trz)3]SnF6n x H2O (NH(2)trz=4-amino-1,2,4-triazole; n=1 (1), n=0.5 (2))
      are new 1D spin-crossover coordination polymers. Compound 2 exhibits an
      incomplete spin transition centred at around 210 K with a thermal hysteresis loop
      approximately 16 K wide. The spin transition of 2 was detected by the Mossbauer
      resonance of the 119Sn atom in the SnF6 (2-) anion primarily on the basis of the
      evolution of its local distortion. Rapid-cooling 57Fe Mossbauer and
      superconducting quantum interference device experiments allow dramatic widening
      of the hysteresis width of 2 from 16 K up to 82 K and also shift the spin
      transition curve into the room temperature region. This unusual behaviour of
      quenched samples on warming is attributed to activation of the molecular motion
      of the anions from a frozen distorted form towards a regular form at temperatures
      well above approximately 210 K. Potential applications of this new family of
      materials are discussed.

PMID- 18327756
TI  - IR spectroscopic properties of H(MeOH)n + clusters in the liquid phase: evidence
      for a proton wire.
AB  - The long-standing problem of understanding the nature of the "excess proton" in
      acidified water is simplified by studying the proton in methanol. The 3D network
      of hydrogen bonds in H(aq) + is reduced to a 1D problem. Infrared spectroscopic
      characterization of linear chain methanol proton solvates in H(CH3OH)n + for n=2
      8 provides insight into some of the puzzling IR spectral features associated with
      O-H-O vibrations. These include the virtual disappearance of otherwise strong
      bands from H-bonded methanol molecules adjacent to symmetrical O-H+-O groups. The
      data indicate that a chain of up to four O--HO bonds either side of this group
      can act as an electrical wire to separate positive charge. This suggests a
      refinement of the Grotthuss proton-hopping mechanism for explaining the
      anomalously high mobility of H+ in H-bonded media.

PMID- 18327757
TI  - Synthesis of platensimycin.
AB  - In modern drug discovery, antibodies or libraries of simple synthetic organic
      compounds, mostly of heterocyclic origin, are favored. Natural products play an
      increasingly inferior role as they are considered structurally too complex,
      limited in quantity, and difficult to synthesize, manipulate, and derivatize.
      Thus it was a sensation when a Merck research group reported that classical
      screening of metabolites from Streptomyces platensis has unearthed a low
      molecular-weight organic compound with remarkable antibiotic properties.

PMID- 18327758
TI  - Chlorophyll breakdown by a biomimetic route.

PMID- 18327759
TI  - Metal and ligand control of sulfenate reactivity: arene ruthenium thiolato-mono-S
      oxides.

PMID- 18327760
TI  - Direct imaging of the MoVTeNbO M1 phase using an aberration-corrected high
      resolution scanning transmission electron microscope.

PMID- 18327761
TI  - Rhodium derivatives of peroxoboronic acids and peroxoboric acid: formation of
      metallatrioxaborolanes from an eta2-peroxo complex.

PMID- 18327762
TI  - Formation of molecular gradients on bipolar electrodes.

PMID- 18327763
TI  - Retina development in zebrafish requires the heparan sulfate proteoglycan agrin.
AB  - Recent studies from our laboratory have begun to elucidate the role of agrin in
      zebrafish development. One agrin morphant phenotype that results from agrin
      knockdown is microphthalmia (reduced eye size). To begin to understand the
      mechanisms underlying the role of agrin in eye development, we have analyzed
      retina development in agrin morphants. Retinal differentiation is impaired in
      agrin morphants, with retinal lamination being disrupted following agrin
      morpholino treatment. Pax 6.1 and Mbx1 gene expression, markers of eye
      development, are markedly reduced in agrin morphants. Formation of the optic
      fiber layer of the zebrafish retina is also impaired, exhibited as both reduced
      size of the optic fiber layer, and disruption of retinal ganglion cell axon
      growth to the optic tectum. The retinotectal topographic projection to the optic
      tectum is perturbed in agrin morphants in association with a marked loss of
      heparan sulfate expression in the retinotectal pathway, with this phenotype
      resembling retinotectal phenotypes observed in mutant zebrafish lacking enzymes
      for heparan sulfate synthesis. Treatment of agrin morphants with a fibroblast
      growth factor (Fgf) receptor inhibitor, rescue of the retinal lamination
      phenotype by transplantation of Fgf8-coated beads, and disruption of both the
      expression of Fgf-dependent genes and activation of ERK in agrin morphants
      provides evidence that agrin modulation of Fgf function contributes to retina
      development. Collectively, these agrin morphant phenotypes provide support for a
      crucial role of agrin in retina development and formation of an ordered
      retinotectal topographic map in the optic tectum of zebrafish.

PMID- 18327764
TI  - Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia
      through inactivation of PI3K.
AB  - Ezrin-radixin-moesin (ERM) proteins are involved in the linkage of membranes to
      theactin filament (F-actin) cytoskeleton. Phosphorylation of the C-terminus
      activates the F-actin binding domain of ERM proteins by preventing the action of
      an autoinhibitory domain. In this study, we investigated whether a growth cone
      collapsing signal, semaphorin 3A (Sema3A), alters the state of ERM C-terminus
      phosphorylation. In the growth cones of dorsal root ganglion axons,
      phosphorylated ERM proteins localize to filopodia. We report that Sema3A inhibits
      ERM protein phosphorylation in growth cone filopodia. Significantly, Sema3A
      decreased ERM phosphorylation prior to the onset of growth cone collapse. Over
      expression of the F-actin binding fragment of ERM proteins, which competes with
      endogenous ERM proteins for binding to F-actin, inhibited filopodial initiation
      and dynamics. Sema3A has been previously shown to inhibit phosphoinositide 3
      kinase (PI3K) activity. Inhibition of PI3K resulted in the loss of phosphorylated
      ERM proteins from growth cone filopodia, and treatment with a PI3K activating
      peptide blocked the effects of Sema3A on ERM phosphorylation. Collectively, these
      observations demonstrate that inactivation of PI3K in response to Sema3A results
      in decreased phosphorylation of ERM proteins in filopodia thereby contributing to
      growth cone collapse.

PMID- 18327765
TI  - Cux-1 and Cux-2 control the development of Reelin expressing cortical
      interneurons.
AB  - Homeodomain transcription factors play important roles in the specification and
      differentiation of neuronal subpopulations. In the cerebral cortex, the
      expression patterns of Cux-1 and Cux-2 in the medial ganglionic eminence (MGE)
      suggest a role for these transcription factors in the development of
      interneurons, a heterogeneous neuronal population. In this report, we describe
      expression of Cux-1 and Cux-2 proteins in Reelin-secreting interneurons of the
      cortical plate, but not in calretinin or parvalbumin subpopulations. The role of
      Cux genes in the development of Reelin positive neurons was studied using Cux-1
      and Cux-2 knockout mice. These experiments demonstrate that Cux-1-/-; Cux-2-/-
      double mutation is embryonically lethal. Although this phenotype is highly
      penetrant, a small proportion of mice develop to birth (P0). Analysis of these
      animals demonstrate that expression of Reelin is completely absent in layers II
      IV of Cux-1-/-; Cux-2-/- double mutant mice, but it is not affected in the cortex
      of Cux-1-/- or Cux-2-/- single mutants. No Cux-1-/-; Cux-2-/- double-mutant were
      collected after P0. Since, GABA-ergic populations mature at late postnatal
      stages, this did not allow us to analyze the expression of subclass specific
      markers and define the affected interneuron subpopulations. Our analysis of Cux-1
      /-; Cux-2-/- double mutant thus demonstrates essential yet redundant roles for
      Cux-1 and Cux-2 in specifying Reelin expressing cortical interneurons.

PMID- 18327766
TI  - Electron microscopic 3D-reconstruction of dendritic spines in cultured
      hippocampal neurons undergoing synaptic plasticity.
AB  - Dendritic spines are assumed to constitute the locus of neuronal plasticity, and
      considerable effort has been focused on attempts to demonstrate that new memories
      are associated with the formation of new spines. However, few studies that have
      documented the appearance of spines after exposure to plasticity-producing
      paradigms could demonstrate that a new spine is touched by a bona fida
      presynaptic terminal. Thus, the functional significance of plastic dendritic
      spine changes is not clearly understood. We have used quantitative time lapse
      confocal imaging of cultured hippocampal neurons before and after their exposure
      to a conditioning medium which activates synaptic NMDA receptors. Following the
      experiment the cultures were prepared for 3D electron microscopic reconstruction
      of visually identified dendritic spines. We found that a majority of new, 1- to 2
      h-old spines was touched by presynaptic terminals. Furthermore, when spines
      disappeared, the parent dendrites were sometime touched by a presynaptic bouton
      at the site where the previously identified spine had been located. We conclude
      that new spines are most likely to be functional and that pruned spines can be
      transformed into shaft synapses and thus maintain their functionality within the
      neuronal network.

PMID- 18327767
TI  - A unique cell population in the mouse olfactory bulb displays nuclear beta
      catenin signaling during development and olfactory sensory neuron regeneration.
AB  - Olfactory sensory neurons (OSNs) in the nose form precise connections with
      neurons in the brain. However, mechanisms that account for the formation of such
      precise neuronal connections are incompletely understood. Recent studies
      implicate the function of Wnt growth factors in the formation of neuronal
      connections. To assess the role of Wnt signaling in the olfactory system, we
      examined the expression of beta-galactosidase (beta-gal) in the TOPGAL mouse, a
      transgenic strain in which beta-gal expression reports the activation of the
      canonical Wnt signaling pathway. In the olfactory epithelium, no beta-gal
      expression was observed at any developmental stages. In the olfactory bulb (OB),
      beta-gal expression was observed in a population of cells located at the
      interface of the olfactory nerve layer and the glomerular layer. The beta-gal
      expression was developmentally regulated with the peak expression occurring at
      late embryonic and early postnatal stages and a greatly reduced expression in
      adulthood. Further, forced OSN regeneration and subsequent reinnervation of the
      OB led to a reactivation of beta-gal expression in mature animals. The temporal
      coincidence between the peak of beta-gal expression and formation of OSN
      connections, together with the spatial localization of these cells, suggests a
      potential role of these cells and canonical Wnt signaling in the formation of OSN
      connections in the OB during development and regeneration.

PMID- 18327768
TI  - Do current beliefs predict hypomanic symptoms beyond personality style? Factor
      analysis of the hypomanic attitudes and positive predictions inventory (HAPPI)
      and its association with hypomanic symptoms in a student population.
AB  - A self-report scale called the Hypomanic Attitudes and Positive Predictions
      Inventory (HAPPI) has been developed to assess cognitions that distinguish
      between bipolar disorder and nonclinical controls (Mansell, 2006; Mansell &
      Jones, 2006). We recruited 191 undergraduate students to assess the associations
      between the HAPPI and self-reported past (MDQ; Hirschfeld et al., 2000) and
      present (ISS; Bauer et al., 1991) bipolar symptoms, and to explore the factor
      structure of the scale. The HAPPI correlated with past and present symptoms
      independently of the BIS/BAS subscales (Carver & White, 1994) and the HPS
      (Eckblad & Chapman, 1986). Five factors of the HAPPI were identified: success
      activation and triumph over fear, activating response style, reduced social
      regulation, loss of control when activated, and catastrophic beliefs about
      internal states. The HAPPI factors showed specific relationships with current
      bipolar symptoms that largely fitted with predictions based on the model. Further
      work is required to establish whether they have a causal role.

PMID- 18327769
TI  - Correction to R. Lemen's review article, 'Asbestos in Brakes: Exposure and Risk
      of Disease'.

PMID- 18327770
TI  - Generation and characterization of alpha-chymase-Cre transgenic mice.
AB  - The Cre-loxP technology allows the introduction of somatic gene alterations in a
      tissue and/or cell type specific manner. The development of transgenes that
      target Cre expression to specific cell types is a critical component in this
      system. Here, we describe the generation and characterization of transgenic mouse
      lines expressing Cre recombinase under the control of the baboon alpha-chymase
      promoter, designated Chm:Cre, in order to direct Cre expression specifically to
      mouse mast cells. Chm:Cre expression was detected in mast cells in lung and colon
      tissue. Cre-mediated recombination in these mice identified a population of
      mature tissue resident mast cells using ROSA26R reporter mice. No Cre-expression
      and Cre-mediated recombination was induced in in vitro generated bone marrow
      derived mast cells or mast cells isolated from the peritoneal cavity indicating
      that Cre-expression under the control of the alpha-chymase promoter is solely
      activated in tissue resident mast cells. These Chm:Cre transgenic mice represent
      a useful tool to specifically inactivate genes of interest in mast cells of these
      tissues.

PMID- 18327771
TI  - Generation and characterization of Csrp1 enhancer-driven tissue-restricted Cre
      recombinase mice.
AB  - Cell type-specific genetic modification using the LoxP/Cre system is a powerful
      tool for genetic analysis of distinct cell lineages. Because of the unique
      arterial smooth muscle-restricted expression of a 5.0 kb cysteine-rich protein
      (Csrp1) enhancer (Lilly et al.,2001, Dev Biol 240:531-547), we hypothesized that
      a transgenic Cre line would prove useful for the smooth muscle lineage-specific
      genetic manipulation. Here we describe a transgenic mouse line, ECsrp1(Cre),
      where Cre is initially specifically expressed in arterial smooth muscle cells.
      Use of the ROSA26R reporter allele confirmed that Cre-mediated recombination in
      vascular smooth muscle cells began at approximately E10.0 and was highly
      proficient. Subsequently, Cre is expressed in restricted skeletal and nonvascular
      smooth muscle lineages. This lineage tracing data is important for future
      conditional knockout studies to understand where and when Cre-mediated deletion
      occurs and where Cre-expressing daughter cells finally localize. Additionally, we
      crossed the ECsrp1(Cre) mice to the ROSA26(-eGFP-DTA) diphtheria toxin A
      expressing mice to genetically ablate ECsrp1(Cre) expressing cells. This
      ECsrp1(Cre) transgenic line should thus prove useful for genetic analysis of
      diverse aspects of cardiovascular morphogenesis and as a general smooth muscle
      lineage deletor line.

PMID- 18327772
TI  - Regulation and function of foxe3 during early zebrafish development.
AB  - In this article, we investigate the expression, regulation, and function of the
      zebrafish forkhead gene foxe3. In wild type embryos, foxe3 is first expressed in
      a crescent-shaped area at the anterior end of the prechordal plate, corresponding
      to the polster. At later stages, the hatching gland, the lens, and the anterior
      pituitary express this gene. Using morpholinos against the zinc finger Kruppel
      like factor 4 (KLF4) we show that foxe3 is regulated differently in the polster
      and in the lens. In the absence of KLF4, expression of foxe3 in the polster is
      not activated, whereas in the lens placode the expression of KLF4 is not required
      for the transcription of foxe3. The expression of foxe3 is also regulated by the
      hedgehog and nodal signaling pathways. foxe3 expression is altered in the
      hedgehog pathway mutants iguana and you-too and the nodal pathway mutant cyclops.
      foxe3 function is necessary for the execution of lens-specific gene expression
      and lens morphogenesis, as the knockdown of foxe3 results in a loss of platelet
      derived growth factor receptor alpha (pdgfralpha) expression and in the
      vacuolization of the lens.

PMID- 18327773
TI  - Pseudogout: an unusual and forgotten metabolic sequela of parathyroidectomy.
AB  - BACKGROUND: Parathyroidectomy is increasingly being performed by otolaryngology
      units. The well-known metabolic sequela is hypocalcaemia; it may be transient or
      permanent depending on presence and/or activity of any residual parathyroid
      tissue. A more unusual metabolic sequela of a parathyroidectomy is the
      development of pseudogout. We summarize the clinical presentation and
      pathophysiology of pseudogout following parathyroidectomy. METHODS: We present a
      case of a 71-year-old woman who developed pseudogout following removal of a
      parathyroid adenoma. RESULTS: Although infrequent, pseudogout predominantly
      occurs in the immediate postoperative period. CONCLUSION: We propose that
      otolaryngology units should be more aware of the unusual sequelae of pseudogout
      following parathyroidectomy; it can lead to a prompt referral and commencement of
      early treatment.

PMID- 18327774
TI  - Fibular free flaps in the management of osteomyelitis of the mandible.
AB  - BACKGROUND: Fibular free flaps are an alternative method in the management of
      chronic osteomyelitis of the mandible without osteoradionecrosis. METHODS: A
      prospective review of 2 cases of chronic osteomyelitis of the mandible managed
      with a fibular free flap was conducted. Patient satisfaction and aesthetic
      results were examined. Follow-up to 9 months was achieved and radiographic
      studies conducted. The current literature on the treatment of chronic
      osteomyelitis of the mandible and the use of free flaps in its management was
      reviewed. RESULTS: The 2 patients with chronic osteomyelitis of the mandible
      whose conservative management failed were effectively treated with the use of a
      fibular free flap reconstruction. CONCLUSION: Microvascular reconstruction with a
      fibular free flap should be considered as a treatment option in the management of
      chronic osteomyelitis of the mandible.

PMID- 18327775
TI  - Small molecule c-MET inhibitor PHA665752: effect on cell growth and motility in
      papillary thyroid carcinoma.
AB  - BACKGROUND: c-Met is upregulated in papillary thyroid carcinoma (PTC) and can be
      an attractive therapeutic target. We tested the effects of the small molecule c
      met inhibitor PHA665752 in blocking c-met-dependent phenotypic effects in PTC
      cell lines. METHODS: PTC patient tissues and cell lines were evaluated for c-met
      expression. The effect of PHA665752 on c-met phosphorylation, downstream
      signaling, hepatocyte growth factor (HGF)-dependent cell growth, and induction of
      apoptosis was studied. The IC(50) of PHA665752 in c-met-expressing PTC cells was
      determined, and growth curves at 0.1x, 1x, and 10x IC(50) concentrations were
      obtained. Poly(ADP-ribose) polymerase (PARP) and caspase-9-processing post
      PHA665752 treatment were studied as markers of apoptosis, and assays analyzing
      HGF-dependent cell invasion and migration in the presence and absence of
      PHA665752 were done. RESULTS: c-Met was upregulated in most of the patient
      tissues with PTC and in many PTC cell lines. PHA665752 specifically inhibited c
      met phosphorylation, c-met-dependent cell growth, signal transduction, cell
      survival, cell invasion, and migration in PTC cells with high c-met. CONCLUSIONS:
      PHA665752 is an effective and specific inhibitor of c-met in PTC cells with high
      levels of c-met expression.

PMID- 18327776
TI  - Free tissue transfer reconstruction of the head and neck at a Veterans Affairs
      hospital.
AB  - BACKGROUND: The Veterans Affairs (VA) population is considered to have generally
      poorer health than its non-VA counterpart. METHODS: We reviewed our experience
      with 55 consecutive patients undergoing free tissue transfers for head and neck
      reconstruction at the Dallas VA Hospital between July 2000 and September 2006,
      with 6 months' follow-up. RESULTS: The overall success rate was 93% (51 of 55
      flaps). Factors affecting flap survival were fasciocutaneous flap versus others
      (p = .01) and minimal versus excessive intraoperative crystalloid administration
      (p = .03). Nine different flaps were used. Major and minor complications occurred
      in 33% (n = 18) and 31% (n = 17) patients, respectively. Average intensive care
      unit and hospital stays were 7.4 and 16.0 days, respectively. CONCLUSIONS: Free
      flaps for head and neck reconstructions in the VA population can be performed
      with excellent success rates. Complication rates and hospital days in this
      population are similar to those of the non-VA populations. Flap selection and
      administration of minimal intraoperative fluids are important.

PMID- 18327777
TI  - Lymphadenomatous carcinoma of the sublingual gland: report of a first case in an
      unusual localization.
AB  - BACKGROUND: Lymphadenomatous carcinoma of the salivary gland is a very rare
      tumor, which hitherto occurred exclusively in the parotid gland. This report
      describes a case of lymphadenomatous carcinoma of the sublingual gland, which is
      thought to be the first report of this special entity. METHODS AND RESULTS: A 36
      year-old man was seen with slowly growing mass on his right floor of mouth. Upon
      surgical removal, the mass was well encapsulated. Microscopic examination
      revealed a biphasic appearance with islands of neoplastic epithelial cells
      presenting against a dense lymphoid stroma, while the epithelial compartment
      showed features of malignancy. During 30-months of close follow-up, there has not
      been any sign of local recurrence or metastasis. CONCLUSION: The clinical
      behavior, the age of the patient, and the sublingual localization differentiate
      this lesion from the sebaceous type, favoring lymphadenomatous carcinoma as a
      distinct clinical entity.

PMID- 18327778
TI  - Transoral laser surgery for supraglottic cancer.
AB  - The goal of treatment for supraglottic cancer is to achieve cure and to preserve
      laryngeal function. Organ preservation strategies include both endoscopic and
      open surgical approaches as well as radiation and chemotherapy. The challenge is
      to select the correct modalities for each patient. Endoscopic procedures should
      be limited to tumors that can be completely visualized during diagnostic
      microlaryngoscopy. If complete resection can be achieved, the oncologic results
      of transoral laser surgery appear to be comparable to those of classic
      supraglottic laryngectomy. In addition, functional results of transoral laser
      resection are superior to those of the conventional open approach, in terms of
      the time required to restore swallowing, tracheotomy rate, incidence of
      pharyngocutaneous fistulae, and shorter hospital stay. The management of the neck
      remains of paramount importance, as survival of patients with supraglottic cancer
      depends more on cervical metastasis than on the primary tumor. Most authors
      advocate bilateral elective neck dissection. However, in selected cases (T1,T2
      clinically negative [N0] lateral supraglottic cancers), ipsilateral selective
      neck dissection could be performed without compromising survival. The authors
      conclude that with careful selection of patients, laser supraglottic laryngectomy
      is a suitable, and often the preferred, treatment option for supraglottic cancer.

PMID- 18327779
TI  - Validation of the performance of a comprehensive genotyping assay panel of single
      nucleotide polymorphisms in drug metabolism enzyme genes.
AB  - A class of genes, known as drug metabolism enzymes (DMEs) are responsible for the
      metabolism and transport of drugs and other xenobiotics. Variation in DME genes
      most likely accounts for a proportion of the variability in drug response in
      humans, and may contribute to complex diseases such as cancer (Nebert DW, Dieter
      MZ. Pharmacology 2000;61:124-135). To date, assessing the extent of this
      variation has proven difficult, especially because of sequence paralogy issues
      that cause difficulty when attempting to genotype polymorphisms in very closely
      related gene families (Murphy MP. Pharmacogenomics 2000;1:115-123; Ingelman
      Sundberg M. Drug Metab Rev 1999;31:449-459). We have developed and genotyped a
      panel of N=2,325 individual TaqMan genotyping assays for polymorphisms in >200
      DME genes; many of the variants in the panel are single nucleotide polymorphisms
      (SNPs) that are of known or putative function (e.g., missense, nonsense or
      frameshift). Using these assays, we have examined genetic variation among several
      groups of populations, including: 1) the two SNP500 Cancer population panels
      (http://snp500cancer.nci.nih.gov; last accessed: 11 December 2007); and 2) the
      panel used in the International HapMap Project panel (www.hapmap.org; last
      accessed: 11 December 2007). We have developed a comprehensive validation
      strategy to ensure reproducibility and accuracy of the assays and estimated minor
      allele frequencies. Here, we present the results of these analyses, which
      strongly suggest that this panel of DME assays are of extremely high quality and
      produce robust, accurate, and reproducible results.

PMID- 18327780
TI  - Prospective trial of the ultrasonic dissector in thyroid surgery.
AB  - BACKGROUND: Use of the ultrasonic dissector in thyroid surgery is becoming more
      prevalent, with reduced operative time and incision size reported. We assessed
      the value of the harmonic scalpel in routine thyroid lobectomy. METHODS: We
      conducted a single blind, prospective pilot study of 52 euthyroid patients
      requiring thyroid lobectomy. Those with lesions not suitable for resection
      through a 4-cm incision, a history of thyroiditis, or uncontrolled thyroid
      dysfunction were excluded. Patients were allocated to 1 of 2 groups: group I (n =
      31), thyroid lobectomies using conventional surgical techniques; or group II (n =
      21), thyroid lobectomies using the ultrasonic dissector. RESULTS: Outcomes for
      the 2 patient groups were comparable. There was no significant difference in
      operative time or incision size. CONCLUSIONS: The ultrasonic dissector does not
      confer any quantifiable benefit in routine thyroid lobectomy when compared with
      conventional techniques. This is the first reported series in which its use has
      not reduced operative time.

PMID- 18327781
TI  - High-dose-rate brachytherapy plus neck dissection for nodal disease.
AB  - BACKGROUND: Regional control for advanced nodal disease has been only marginally
      affected by concurrent chemoradiation, hyperfractionation, concomitant boost, or
      accelerated external radiation. METHODS: Twenty-five necks in 24 patients
      received brachytherapy treatment (20 Gy in 10 twice-daily fractions) in addition
      to external radiation, neck dissection +/- chemotherapy. Indications for
      brachytherapy included initial treatment of bulky disease (n = 12), recurrence of
      neck disease in a previously treated patient with at least a 3-month disease-free
      interval (n = 6), persistent disease after a curative efforts (n = 4), inadequate
      external radiation (ie, <40 Gy) due to either intolerance or noncompliance (n =
      3). RESULTS: Overall actuarial regional control was 67% at 2 years. Regional
      control for those receiving brachytherapy as part of their initial treatment was
      82% despite a mean nodal diameter of 8.7 cm (range, 5-15 cm). The 2-year
      actuarial regional control was 56% for the patients with a disease-free interval
      of at least 3 years. CONCLUSION: High-dose-rate brachytherapy produced excellent
      regional control. (c) 2008 Wiley Periodicals, Inc. Head Neck, 2008.

PMID- 18327782
TI  - Synovial sarcoma presenting as a parotid mass: case report and review of
      literature.
AB  - BACKGROUND: Synovial sarcoma is an unusual neoplasm of mesenchymal derivation,
      which is uncommon in the head and neck sites. In the parotid gland, it is most
      likely to be misdiagnosed as a myoepithelial, primary mesenchymal, or metastatic
      neoplasm. METHODS: We report a case of synovial sarcoma in a young woman who was
      seen with temporomandibular joint symptoms with a 10-year history. A review of
      the literature was undertaken to highlight the radiologic and histologic features
      that help in diagnosis as well as the suggested therapeutic protocols most likely
      to ensure better survival. RESULTS: Radiologic and histologic studies of the
      parotid mass led to a diagnosis of synovial sarcoma. A total parotidectomy was
      performed, and the individual remains tumor free at 36 months. CONCLUSIONS:
      Review of the literature suggests an aggressive long-term outcome for synovial
      sarcoma and advocates early diagnosis and radical surgical excision for a
      favorable prognosis.

PMID- 18327783
TI  - Solitary extramedullary plasmacytoma of the head and neck--long-term outcome
      analysis of 68 cases.
AB  - BACKGROUND: Head and neck solitary extramedullary plasmacytomas are rare plasma
      cell neoplasms. Literature review reveals only small numbers of reports. The
      objective was to review our experience with treating patients with this neoplasm.
      METHODS: A retrospective chart review between 1960 and 2000 was performed. Sixty
      eight patients with head and neck extramedullary plasmacytomas were included.
      RESULTS: The sinonasal tract was the most common site. Thirty-nine patients were
      treated with radiation, 8 with surgery, 14 with surgery and radiation, and 3 with
      chemoradiation. Median follow-up was 8 years. The 5-year local recurrence-free
      rate (LRFR) was 81%. There was a trend toward improved LRFR in patients treated
      primarily with radiation. Regional recurrence at 5 years was 5%. Multiple myeloma
      developed in 23% of patients. The 5-year survival was 76%. CONCLUSIONS: Radiation
      is the treatment of choice with surgery reserved for large tumors and extensive
      bone destruction. Long-term follow-up is essential because local recurrence and
      disseminated disease can occur many years postdiagnosis.

PMID- 18327784
TI  - Decoupling functionalization from sensor array assembly using detachable
      cantilevers.
AB  - Cantilevers are useful as sensor devices with high sensitivity and have shown
      great promise for dense, multianalyte arrays. One of the difficulties has been
      the fabrication of multianalyte arrays that are capable of the simultaneous
      detection of a wide range of chemical and biological species. Functionalization
      procedures for one class of analytes are often incompatible with other classes
      and cross contamination is a significant concern when ink-jet deposition
      processes are used. In this study, we used surface micromachined cantilevers
      designed and fabricated using Sandia National Laboratories SUMMiT V MEMS process.
      The cantilevers are fabricated with a base that can be detached from the parent
      substrate after functionalization and mounted into a daughter array. We have
      utilized an IBM-fabricated 8-cantilever array chip as our daughter substrate due
      to its compatibility with a Scentris 8-cantilever readout system. Our initial
      work demonstrates that this is a feasible procedure for decoupling
      functionalization from array assembly.

PMID- 18327785
TI  - The clinical spectrum associated with a chromosome 17 short arm proximal
      duplication (dup 17p11.2) in three patients.
AB  - The p11.2-p12 region of human chromosome 17 is gene rich and composed of at least
      two genomically unstable domains: the Smith-Magenis syndrome region (17p11.2) and
      the Charcot-Marie-Tooth region (17p12), both of which are flanked by several low
      copy repeat sequences. Homologous recombination between these flanking repeats
      results in either deletion- or duplication-associated phenotypes caused by a gene
      dosage effect. We report on the clinical phenotype of three patients presenting
      with either a 17p11.2 or 17p11.2p12 duplication, revealed by chromosome analysis
      and confirmed by fluorescent in situ hybridization analysis, high resolution
      genomic analysis of the 17p region using oligonucleotide array comparative
      genomic hybridization, and molecular studies with microsatellite markers. Two
      patients carry the 17p11.2 duplication, while the third one shows a larger
      duplication including the 17p12 region. The facial features observed in our
      patients include triangular face, full cheeks, smooth philtrum, thin upper lip,
      dental malocclusion, irregular eyebrows, and sparse hair, all of which are
      consistent with the pure proximal dup 17p phenotype. The patients' other clinical
      features are compared with previously published cases.

PMID- 18327786
TI  - A mouse model for tracking nigrostriatal dopamine neuron axon growth.
AB  - The midbrain dopaminergic system, which consists of neurons of the substantia
      nigra and the ventral tegmental area, is a subject of intense interest, since the
      loss of neurons from the substantia nigra results in motor disorders
      characteristic of Parkinson's disease. We have generated a knock-in reporter
      mouse line with the tau-lacZ fusion gene inserted into the Pitx3 locus via
      homologous recombination. This approach permitted the visualisation of midbrain
      specific dopaminergic axonal tracts from both the substantia nigra and the
      ventral tegmental area in phenotypically normal heterozygous Pitx3-taulacZ brain
      tissues, either in situ or following culture in vitro, by a simple and sensitive
      beta-galactosidase enzyme reaction. Thus the Pitx3-taulacZ mice could serve as a
      valuable tool for the identification of molecules regulating midbrain
      dopaminergic neuritogenesis, either in vivo in combination with genetic
      manipulation in mice, or in vitro using organ cultures.

PMID- 18327787
TI  - Alternative promoter usage generates multiple evolutionarily conserved isoforms
      of Drosophila DOA kinase.
AB  - The unique LAMMER (or Clk) protein kinase of Drosophila is encoded at the Doa
      locus. To better understand the pleiotropic effects of Doa mutations, we describe
      the structure and expression of the multiple RNA and protein products of the
      locus, as well as their evolutionary conservation among Drosophila. The gene
      produces at least six different protein isoforms, primarily through alternative
      promoter usage, generating kinases with virtually identical catalytic domains but
      variable N-terminal noncatalytic domains. The single known alternative splicing
      event generates a kinase with the insertion of six additional amino-acids in the
      catalytic domain. Two independent predicted genes nested within Doa introns
      actually encode additional alternative N-termini of the locus. An alternative
      polyadenylation site utilized exclusively during early embryogenesis generates a
      transcript with a short half-life, apparently to ensure a "burst" of kinase
      expression at the onset of development. Ecdysone induction of Doa transcripts
      affects all isoforms during pupariation. Finally, extensive conservation of amino
      acid sequences of both the catalytic and N-terminal noncatalytic exons observed
      in alignments between D. melanogaster exons and the genome sequences of 11 other
      Drosophila species suggest that the multiple isoforms serve important and
      nonredundant functions.

PMID- 18327788
TI  - Simultaneous Cre-mediated conditional knockdown of two genes in mice.
AB  - One of the most promising techniques to manipulate gene expression in vivo is the
      use of RNA interference (RNAi). Various approaches were developed to use RNAi in
      the mouse, including vector-based expression of short hairpin RNAs and the
      Cre/loxP recombination system. We combined these two approaches to create a
      vector system that allows the time- and tissue-specific control of two genes at
      the same time. For this purpose two independent conditional shRNA expression
      cassettes are combined into a single construct. By the use of different,
      incompatible pairs of lox sites that flank transcriptional stop cassettes, Cre
      recombinase can independently activate both short hairpins. Here, we show that
      Cre simultaneously activates both shRNAs in vitro and in vivo. We applied this
      technique to silence the widely coexpressed gene pairs Gsk-3alpha/Gsk-3beta and
      Erk1/Erk2 in murine embryonic stem cells and in the mouse brain.

PMID- 18327789
TI  - Dynamic rearrangement of surface proteins is essential for cytokinesis.
AB  - Cytokinesis is a complex process that involves dynamic cortical rearrangement.
      Our recent time-lapse recordings of the mouse egg unexpectedly revealed a high
      motility of the second polar body (2pb). Experiments to address its underlying
      mechanism show that neither mechanical compression by the zona pellucida nor the
      connection via the mid-body is required for the 2pb movement. Time-lapse
      recordings establish that the 2pb moves together with the cell membrane. These
      recordings, in which cell surface proteins are labeled with fluorescent latex
      microbeads or monovalent antibodies against whole mouse proteins, indicate that
      the majority of the surface proteins dynamically accumulate in the cleavage
      furrow at every cell division. Comparable dynamics of the cell surface proteins,
      and specifically of E-cadherin, are also observed in cultured epithelial cells.
      The surface protein dynamics are closely correlated with, and dependent on, those
      of the underlying cortical actin. The cortical actin network may form a scaffold
      for membrane proteins and thereby transfer them during contractile ring formation
      toward the cleavage furrow. Immobilization of surface proteins by tetravalent
      lectin-mediated crosslinking results in the failure of cleavage, demonstrating
      that the observed protein dynamics are essential for cytokinesis. We propose that
      dynamic rearrangement of the cell surface proteins is a common feature of
      cytokinesis, playing a key role in modifying the mechanical properties of the
      cell membrane during cortical ingression.

PMID- 18327790
TI  - Lytic lesions in the femoral neck: Importance of location and evaluation of a
      novel minimally invasive repair technique.
AB  - Proximal femoral metastases can lead to pathologic fracture. The goals of this
      study were to improve guidelines for assessing pathologic hip fracture risk by
      quantifying the effect of location of femoral neck metastases on hip strength
      under single-limb stance loading and to evaluate the effectiveness of a proposed
      minimally invasive surgical repair technique for restoring hip strength. Twelve
      matched pairs of human cadaveric proximal femora were used to create a total of
      564 finite element models before and after introduction and repair of simulated
      lytic defects, modeled as spherical voids, at various locations within the
      femoral neck. Defect site greatly affected hip strength (p < 0.001). Defects in
      the inferomedial aspect of the neck and in the dense trabecular bone near the
      base of the femoral head had the greatest effect, with hip strengths 23% to 72%
      and 43% to 64% that of the intact strength, respectively, for 20-mm diameter
      defects. Even so, the proposed percutaneous repair technique restored static
      strength of femora with defects at all of the studied locations. These findings
      may lead to a reduction in the number of patients who suffer a preventable
      pathologic fracture, a decreased likelihood of unnecessary surgery, and a less
      invasive prophylactic surgical procedure.

PMID- 18327791
TI  - Fine-needle aspiration biopsy of the breast: obsolete or state of the art?

PMID- 18327792
TI  - In vivo cartilage contact deformation of human ankle joints under full body
      weight.
AB  - Quantitative data on in vivo deformation of articular cartilage is important for
      understanding the articular joint function and the etiology of degenerative joint
      diseases such as osteoarthritis. This study experimentally determined the in vivo
      cartilage thickness distribution and articular cartilage contact strain
      distribution in human ankle joints under full body weight loading conditions
      using a combined dual fluoroscopic and magnetic resonance imaging technique. The
      average cartilage thickness with the joint non-weight bearing was found to be
      1.43 mm +/- 0.15 mm and 1.42 mm +/- 0.18 mm in the distal tibial and proximal
      talar cartilage layers, respectively. During weight bearing on a single leg, the
      strain distribution data revealed that 42.4% +/- 15.7% of the contact area had
      contact strain higher than 15% in the ankle joint. Peak cartilage contact strain
      reached 34.5% +/- 7.3%. This quantitative data on in vivo human cartilage
      morphology and deformation demonstrated that the cartilage may undergo large
      deformations under the loading conditions experienced in human ankle joints
      during daily activities. The in vivo cartilage contact deformation can be used as
      displacement boundary conditions in three-dimensional (3D) finite element models
      of the joint to calculate in vivo 3D articular cartilage contact stress/strain
      distributions.

PMID- 18327793
TI  - Chondrocytes harvested from osteochondritis dissecans cartilage are able to
      undergo limited in vitro chondrogenesis despite having perturbations of cell
      phenotype in vivo.
AB  - Our objective was to characterize the variation in gene expression for key genes
      associated with chondrogenic phenotype of osteochondrosis (OC)-affected and
      normal chondrocytes, and to identify whether OC chondrocytes can redifferentiate
      and regain a phenotype similar to normal chondrocytes if appropriate chondrogenic
      signals are given. Equine articular cartilage removed at surgery to treat
      clinically significant OC lesions was collected (n = 10), and the gene expression
      evaluated and compared to aged-matched normal samples (n = 10). Cartilage was
      harvested from normal (n = 4) and OC (n = 3) joints from horses at necropsy.
      Chondrogenic pellet cultures were established following monolayer proliferation.
      After 14 days in culture, the pellets were assessed by histochemical and pellet
      weight analysis, assay of glycosaminoglycan (GAG) content, and gene expression.
      Chondrocytes from OC cartilage expressed significantly more Coll-I, -II, -III,
      and -X than chondrocytes from normal cartilage (all p < 0.0001). Furthermore, OC
      chondrocytes expressed significantly more MMP-13, ADAMTS-4 (both p < 0.0001), and
      TIMP-1 (p < 0.001) and significantly less TIMP-2 and TIMP-3. Pellets created from
      OC chondrocytes contained significantly less GAG (p = 0.0069) and expressed
      significantly less Sox9 and significantly more superficial zone protein (SZP) (p
      = 0.0105) than pellets created from normal cartilage. The results suggest that
      chondrocytes from OC cartilage at the time of surgical treatment have
      perturbations in phenotype compared to cells from normal cartilage. Despite these
      differences, following monolayer expansion and pellet culture under chondrogenic
      conditions, chondrocytes derived from OC cartilage retain some ability to undergo
      chondrogenic differentiation and synthesize an appropriate cartilage-like matrix.
      However, this chondrogenic differentiation potential is inferior to that seen in
      aged-matched normal chondrocytes.

PMID- 18327794
TI  - Antisense oligonucleotide targeting TNF-alpha can suppress Co-Cr-Mo particle
      induced osteolysis.
AB  - The most common cause of implant failure in joint replacement is aseptic
      loosening due to particle-induced osteolysis. TNF-alpha has been shown to be one
      of the key factors in the process of osteoclastogenesis. Anti-TNF agents are
      useful in the treatment of joint inflammation related to osteolysis. This study
      investigated the effect of a single subcutaneous dose of an antisense
      oligonucleotide (ASO) on particle-induced osteolysis. We utilized the murine
      calvaria osteolysis model in C57BL/J6 mice. Bone resorption was measured by the
      toluidine blue staining. Osteoclasts were detected by tartrate resistant acid
      phosphatase (TRAP) staining assay and were quantified by a TRAP quantification
      kit. Results show that bone resorption is 0.347 +/- 0.09 mm(2) in mice with
      particle implantation, and decreased to 0.123 +/- 0.05 mm(2) and 0.052 +/- 0.02
      mm(2) after ASO treatment with low and high doses, respectively. The number of
      osteoclasts in animal calvaria treated with ASO is reduced compared with that of
      untreated animals, and the quantification results indicate that about 90% of
      osteoclastogenesis is suppressed by the ASO. In addition, the osteoclastogenesis
      can be reestablished by the addition of TNF-alpha. In conclusion, we demonstrate
      that the antisense oligonucleotide targeting to TNF-alpha can suppress osteolysis
      induced by metal particles in a murine calvaria model. This new finding may be of
      value in the search for novel therapeutic methods for implant loosening.

PMID- 18327795
TI  - Knee joint biomechanics following arthroscopic partial meniscectomy.
AB  - We investigated spatiotemporal data, joint kinematics, and joint kinetics during
      gait in a group of subjects who had recently undergone arthroscopic partial
      meniscectomy and compared the results to those of healthy controls. Gait analysis
      was performed on 105 pain-free meniscectomy patients and 47 controls, walking at
      a self-selected speed. The meniscectomy population was comparable to controls in
      spatiotemporal parameters and knee kinematics. However, they had reduced range of
      motion (ROM) and lower peak moments in the sagittal plane on the operated limb
      compared to the nonoperated limb. Compared to controls, the meniscectomy patients
      had significantly larger knee adduction moments over stance, even after
      accounting for their greater body weight. These differences likely increase
      articular loads on the medial compartment of the tibiofemoral joint and may
      contribute to the high risk of knee osteoarthritis following arthroscopic
      meniscal surgery.

PMID- 18327796
TI  - Effects of a bioscaffold on collagen fibrillogenesis in healing medial collateral
      ligament in rabbits.
AB  - Bioscaffolds have been successfully used to improve the healing of ligaments and
      tendons. In a rabbit model, the application of porcine small intestine submucosa
      (SIS) to the healing medial collateral ligament (MCL) resulted in improved
      mechanical properties with the formation of larger collagen fibrils. Thus, the
      objective of the study was to find out whether the SIS bioscaffold could improve
      the gene expressions of fibrillogenesis-related molecules, specifically, collagen
      types I, III, V, and small leucine-rich proteoglycans including decorin,
      biglycan, lumican, and fibromodulin, as well as collagen fibril morphology and
      organization, in the healing rabbit MCL at an early time point (6 weeks
      postinjury). Twenty skeletally mature rabbits were equally divided into two
      groups. In the SIS-treated group, a 6-mm gap was surgically created and a layer
      of SIS was sutured to cover the gap, whereas the gap was left open in the
      nontreated group. At 6 weeks postinjury, Masson's trichrome staining showed that
      the SIS-treated group had more regularly aligned collagen fibers and cells.
      Transmission electron microscopy revealed that the SIS-treated group had larger
      collagen fibrils with a diameter distribution from 24 to 120 nm, whereas the
      nontreated group had only small collagen fibrils (ranging from 26 to 87 nm, p <
      0.05). Finally, the quantitative real-time PCR showed that the mRNAs of collagen
      type V, decorin, biglycan, and lumican in the SIS-treated group were 41, 58, 51,
      and 43% lower than those in the nontreated group, respectively (p < 0.05). Such
      significant reduction in the gene expressions are closely related to the improved
      morphological characteristics, which are known to be coupled with better
      mechanical properties, as previously reported in longer term studies.

PMID- 18327797
TI  - Variation of cyclic strain parameters regulates development of elastic modulus in
      fibroblast/substrate constructs.
AB  - Dynamic mechanical culture systems are a widely studied approach for improving
      the functional mechanical properties of tissue engineering constructs intended
      for loading-bearing orthopedic applications such as tendon/ligament
      reconstruction. The design of effective mechanical stimulation regimes requires a
      fundamental understanding of the effects of cyclic strain parameters on the
      resulting construct properties. Toward this end, these studies employed a modular
      cyclic strain bioreactor system and fibroblast-seeded, porous polyurethane
      substrates to systematically investigate the effect of varying cyclic strain
      amplitude, rate, frequency, and daily cycle number on construct mechanical
      properties. Significant differences were observed in response to variation of all
      four loading parameters tested. In general, the highest values of elastic modulus
      within each experimental group were observed at low to intermediate values of the
      experimental variables tested, corresponding to the low to subphysiological range
      (2.5% strain amplitude, 25%/s strain rate, 0.1-0.5 Hz frequency, and 7,200-28,800
      cycles/day). These studies demonstrate that fibroblasts are sensitive and
      responsive to multiple characteristics of their mechanical environment, and
      suggest that systematic optimization of dynamic culture conditions may be useful
      for the acceleration of construct maturation and mechanical function.

PMID- 18327798
TI  - Increased IL-1beta expression and myofibroblast recruitment in subacromial bursa
      is associated with rotator cuff lesions with shoulder stiffness.
AB  - We evaluated whether proinflammatory cytokine expression and myofibroblast
      recruitment in subacromial bursa was linked to rotator cuff lesions with shoulder
      stiffness. We analyzed expressions of IL-1beta, IL-6, and TNF-alpha in
      subacromial bursa and joint fluid collected from 14 patients with cuff tears with
      stiffness as a study group (Group I) and 14 patients with rotator cuff tears
      without shoulder stiffness as a control group (Group II) using real-time RT-PCR,
      immunohistochemistry, and ELISA. Myofibroblast apoptosis in subacromial bursa was
      analyzed using terminal deoxynucleotidyl transferase -mediated deoxyuridine
      triphosphate-biotin nick end-labeling (TUNEL) and alpha-smooth muscle actin
      immunofluorescence staining. Shoulder function was evaluated using the Constant
      score. Group I had higher mRNA expression (p < 0.001) and immunoreactivities (p <
      0.001) of IL-1beta. They also had higher levels of IL-1beta, IL-6, and TNF-alpha
      in joint fluid. Increased IL-1beta mRNA expression in the subacromial bursa and
      IL-1beta levels in joint fluid were correlated with a preoperative deficit in
      shoulder motion (p < 0.001) and preoperative Constant scores (p < 0.001).
      Immunofluorescence observations showed that Group I subjects had more
      myofibroblasts (p < 0.001) than Group II. In Group II, a significant correlation
      was found between apoptotic myofibroblasts and total myofibroblasts (p = 0.002),
      but not in Group I (p = 0.510). Increased expression of IL-1beta and
      myofibroblast recruitment in the subacromial bursa in rotator cuff lesions are
      linked to shoulder stiffness.

PMID- 18327799
TI  - Experimental and model determination of human intervertebral disc
      osmoviscoelasticity.
AB  - Finite element (FE) models have become an important tool to study load
      distribution in the healthy and degenerated disc. However, model predictions
      require accurate constitutive laws and material properties. As the mechanical
      properties of the intervertebral disc are regulated by its biochemical
      composition and fiber-reinforced structure, the relationship between the
      constitutive behavior of the tissue and its composition requires careful
      consideration. While numerous studies have investigated the annulus fibrosus
      compressive and tensile properties, specific conditions required to determine
      model parameters for the osmoviscoelastic model are unavailable. Therefore, the
      objectives of this study were (1) to complement the existing material testing in
      the literature with confined compression and tensile tests on human annulus
      fibrosus and (2) to use these data, together with existing nucleus pulposus
      compression data to tune a composition-based, osmoviscoelastic material
      constitutive law. The osmoviscoelastic material constitutive law and the
      experimental data were used to describe the fiber and nonfiber properties of the
      human disc. The compressive material properties of normal disc tissue were G(m) =
      1.23 MPa, M = 1.57, and alpha = 1.964 x 10(-16) m(4)/Ns; the tensile fiber
      material parameters were E(0) = 77.0 MPa; E(epsilon) = 500 MPa, and eta = 1.8 x
      10(3) MPa(-s). The goodness of fit ranged from 0.88 to 0.96 for the four
      experimental conditions evaluated. The constitutive law emphasized the
      interdependency of the strong swelling ability of the tissue and the viscoelastic
      nature of the collagen fibers. This is especially important for numerical models
      to further study the load sharing behavior with regard to disc degeneration and
      regeneration.

PMID- 18327800
TI  - Upregulation of alpha-skeletal muscle actin and myosin heavy polypeptide gene
      products in degenerating rotator cuff muscles.
AB  - Impaired function of shoulder muscles, resulting from rotator cuff tears, is
      associated with abnormal deposition of fat in muscle tissue, but corresponding
      cellular and molecular mechanisms, likely reflected by altered gene expression
      profiles, are largely unknown. Here, an analysis of muscle gene expression was
      carried out by semiquantitative RT-PCR in total RNA extracts of supraspinatus
      biopsies collected from 60 patients prior to shoulder surgery. A significant
      increase of alpha-skeletal muscle actin (p = 0.0115) and of myosin heavy
      polypeptide 1 (p = 0.0147) gene transcripts was observed in parallel with
      progressive fat deposition in the muscle, assessed on parasagittal T1-weighted
      turbo-spin-echo magnetic resonance images according to Goutallier. Upregulation
      of alpha-skeletal muscle actin and of myosin heavy polypeptide-1 has been
      reported to be associated with increased muscle tissue metabolism and oxidative
      stress. The findings of the present study, therefore, challenge the hypothesis
      that increased fat deposition in rotator cuff muscle after injury reflects muscle
      degeneration.

PMID- 18327801
TI  - Correlates of patient satisfaction and provider trust after breast-conserving
      surgery.
AB  - BACKGROUND: Although breast-conserving therapy (BCS) is considered the standard
      of care for early-stage breast cancer, up to 20% of patients are dissatisfied.
      The effect of treatment-related factors on patient satisfaction with their
      healthcare experiences is unclear. METHODS: All BCS patients at the University of
      Michigan Medical Center who were treated between January 2002 and May 2006 were
      surveyed (n=714; response rate, 79.5%). Patients were queried regarding 4 aspects
      of their decision for surgery: satisfaction with the decision, decision regret,
      decisional conflict, and trust in surgeons. Independent variables included the
      number of re-excisions, the occurrence of postoperative complications, and
      postoperative breast appearance, which was assessed by using the Breast Cancer
      Treatment and Outcomes scale. Multiple logistic regression was used to assess the
      effect of the independent variables on each outcome controlling for demographic
      and clinical characteristics. RESULTS: Breast asymmetry after BCS was correlated
      significantly with patient satisfaction with their treatment experiences and
      patient distrust in surgeons. Women who reported pronounced asymmetry were
      significantly less likely to be satisfied with the decision for surgery compared
      with women who reported minimal asymmetry (odds ratio [OR], 0.43; 95% confidence
      interval [95% CI], 0.21-0.89). Women with pronounced asymmetry were less likely
      to be certain about their surgical decision (OR, 0.36; 95% CI, 0.21-0.60) and to
      believe that they were prepared to make the decision for surgery (OR, 0.25; 95%
      CI, 0.14-0.43). Increasing breast asymmetry was associated with higher surgeon
      distrust scores (2.14 vs 2.30 vs 2.35; P= .04) and with the occurrence of
      postoperative complications (distrust score: 2.23 vs 2.35; P= .03). Reoperation
      after BCS was not associated with patient satisfaction or trust in providers.
      CONCLUSIONS: Esthetic result after BCS was associated more profoundly with
      aspects of satisfaction than either surgical therapy or the occurrence of
      postoperative complications. The current findings indicated that surgeons who
      care for patients with breast cancer should identify the women at an increased
      risk for breast asymmetry preoperatively to effectively address their
      expectations of treatment outcomes.

PMID- 18327802
TI  - A computerized analysis-by-synthesis algorithm improves precision of linear wear
      measurements in total hip replacements.
AB  - Precision is important if small polyethylene wear rates are to be detected early
      and in small sample sizes. Using an automatic, computerized algorithm relying on
      a synthetic X-ray generated from a computer-assisted design (CAD) model of the
      implant may significantly improve precision of linear wear measurements. We
      compared this method to provide improved in vivo precision compared to the widely
      used Hip Analysis Suite software (version 8.0.1.7). Two anterior-posterior pelvic
      X-rays were taken on the same day of 18 total hip implants, and wear was measured
      by three observers using the two methods. Expected real wear was zero and defined
      as a reference value. Two sources of variability were estimated: one due to the
      instrument, and one due to different operators. A Wilcoxon Signed Rank Test was
      used for statistical comparisons. The overall precision (instrument variability
      and multioperator variability) given a 95% precision limit was significantly
      higher (p < 0.001) using the proposed method (+/-0.15 mm) when compared to the
      Hip Analysis Suite (+/-0.84 mm). Due to the availability of the full CAD data of
      the implant and to further automation of the measuring process, the newly
      proposed method provided improved precision in measuring polyethylene wear.

PMID- 18327803
TI  - Gradual stretching of the proximal nerve stump induces the growth of regenerating
      sprouts in rats.
AB  - We investigated the effect of direct gradual stretching on the proximal nerve
      stump morphologically. A 10-mm-long nerve segment was resected from the sciatic
      nerve of a rat. The end of the proximal nerve stump was fixed to a small ring and
      the marking suture was placed at a point 1 mm proximal to the ring. Then, the
      nerve stump was lengthened at a rate of 1 mm/day via a stretching of the ring
      using an original external device. After a stretching of 20 days, the distance
      from the ring to the marking suture became 12 mm. Whereas large mature myelinated
      axons were observed in the proximal part of the marking, only small axons with
      thin myelin sheath were observed in the distal part, and the mean axonal diameter
      showed a significant difference between the two parts. Moreover, the mean
      internodal length was 172.4 +/- 13.4 microm in the distal part of the marking and
      1019.0 +/- 56.2 microm in the proximal part. The internodal length also showed a
      significant difference between the two parts. Thus, the axonal diameter and
      internodal length were consistent with the characteristics of regenerating axons
      in the distal part. Furthermore, ultrastructural analysis also showed the
      histological characteristics of axonal regeneration. Thus, a transected proximal
      nerve stump may be lengthened by axonal regeneration during gradual stretching,
      and the stimulus of mechanical stretching may induce the growth of regenerating
      axons.

PMID- 18327804
TI  - Association of interindividual differences in p14ARF promoter methylation with
      single nucleotide polymorphism in primary colorectal cancer.
AB  - BACKGROUND: CpG island hypermethylation has been reported at the promoter region
      of many tumor suppressor genes in colorectal cancers. However, there are
      significant interindividual differences in the degree of DNA methylation in
      colorectal cancers. The objective of the current study was to understand whether
      single nucleotide polymorphisms (SNPs) around the promoter of a gene are
      implicated in the interindividual differences of CpG island hypermethylation.
      METHODS: Promoter methylation of the p14(ARF) gene and messenger RNA (mRNA)
      expression levels of p14(ARF), DNA methyltransferase 1 (DNMT1), and DNMT3b were
      investigated by using methylation-specific polymerase chain reaction (PCR)
      analysis (MSP) and quantitative real-time PCR analysis in fresh tissues from 188
      patients with colorectal cancer. SNPs around the p14(ARF) promoter were genotyped
      in DNA from peripheral blood lymphocytes in 300 healthy individuals and in 188
      patients with colorectal cancer by using matrix-assisted laser
      desorption/ionization mass spectrometry. RESULTS: p14(ARF) methylation was
      present in 61 of 188 colorectal cancers (32%). Fourteen SNPs among the 20
      candidate SNPs were identified as monomorphic in the Korean population studied.
      Two individual SNPs (-4256 thymine to cytosine [T-->C] and -1477 guanine to
      adenine [G-->A]), which were in strong linkage disequilibrium (|D'|=0.99;
      correlation coefficient [r(2)]=0.95), were associated significantly with p14(ARF)
      methylation. Patients who had the CC variant at the-4256 locus or the AA variant
      at the -1477 locus had 2.42 times (95% confidence interval [95% CI], 1.07-5.46; P
      = .03) and 2.47 times (95% CI, 1.09-5.56; P= .03) greater risk of p14(ARF)
      methylation than patients who had the TT or GG homozygote, respectively, after
      adjusting for mRNA levels of DNMTs. Four major haplotypes were identified within
      a block (-4256 T-->C, -3631 T-->C, -1477 G-->A, and +20,188 T-->C). p14(ARF)
      promoter methylation also was associated significantly with the CCAT haplotype
      (odds ratio [OR], 8.31; 95% CI, 2.43-28.41; P= .0007) and the CTAC haplotype (OR,
      9.71; 95% CI, 1.09-86.24; P= .04). CONCLUSIONS: The current results suggested
      that SNPs around the p14(ARF) promoter region may be responsible for the
      interindividual susceptibility to p14(ARF) promoter methylation among individuals
      with colorectal cancer.

PMID- 18327805
TI  - N-glycoprotein profiling of lung adenocarcinoma pleural effusions by shotgun
      proteomics.
AB  - BACKGROUND: Malignant pleural effusion of advanced lung adenocarcinoma may be a
      valid source for detection of biomarkers, such as N-glycosylated proteins (N-GP),
      because tumor cells grow during weeks in this liquid. The authors aimed for
      creation of N-GP effusion profiles from routine cytology specimens to detect
      relevant biomarkers. METHODS: Hundred microliters of malignant pleural effusions
      of 5 patients with lung adenocarcinoma and 5 nonmalignant controls were used for
      triplicate N-GP capture by solid-phase extraction. After trypsin digest and
      PNGase F release, a liquid chromatography separation connected online to a tandem
      mass spectrometer was performed by liquid chromatography/tandem mass spectrometry
      (LC/MS/MS). RESULTS: In the total of 10 samples, 170 and 278 nonredundant
      proteins were detected with probabilities of >or=.9 and >or=.5, respectively. The
      specificity for the N-glycomotif was 88% at P >or= .9. Penetration into the
      moderate to low protein concentration range (microg-ng/mL) occurred, and several
      proteins associated with tumor progression or metastasis were identified,
      including CA-125, CD44, CD166, lysosome-associated membrane glycoprotein 2 (LAMP
      2), multimerin 2, and periostin. MS identifications were correlated with the
      corresponding immunoreactivity in either effusion fluid or tumor tissue.
      CONCLUSIONS: In conclusion, reduction of sample complexity by N-GP capturing
      allows detection of proteins in the mug to ng/mL range. Pleural effusion is a
      useful source for biomarker research in lung cancer.

PMID- 18327806
TI  - Pilot study of combination chemotherapy of S-1, a novel oral DPD inhibitor, and
      interferon-alpha for advanced hepatocellular carcinoma with extrahepatic
      metastasis.
AB  - BACKGROUND: To the authors' knowledge, there is no effective therapy for
      extrahepatic metastasis of hepatocellular carcinoma (HCC). In a pilot study, the
      results of combination therapy of S-1, a novel oral dehydropyrimidine
      dehydrogenase (DPD) inhibitor, and interferon-alpha (IFN-alpha) are reported for
      HCC patients with extrahepatic metastasis. METHODS: Twelve patients with
      extrahepatic metastasis of HCC were enrolled in the pilot study. S-1 was
      administered orally at a dose based on body surface area, twice daily after a
      meal, for 4 weeks. IFN-alpha was injected subcutaneously on Days 1, 3, and 5 of
      each week. One course consisted of consecutive administration for 28 days
      followed by 14 days rest. RESULTS: An objective response was observed in 3 (25%)
      of 12 patients. The overall 1-year survival rate was 61.7%. Grade 3
      leukocytopenia was observed in 1 patient (8.3%). No severe toxicity or treatment
      related deaths were observed. CONCLUSIONS: The combination therapy of S-1 and IFN
      alpha appears to be highly efficacious, with low toxicity in patients with
      extrahepatic metastases of HCC. The combination chemotherapy of oral S-1 and
      subcutaneous IFN-alpha is a potentially promising treatment strategy for advanced
      HCC with extrahepatic metastasis.

PMID- 18327807
TI  - Effect of NKISK on tendon lengthening: an in vivo model for various clinically
      applicable dosing regimens.
AB  - One proposed mechanism of tendon lengthening is the "sliding fibril" hypothesis,
      in which tendons lengthen through the sliding of discontinuous fibrils after
      release of decorin-fibronectin interfibrillar bonds. The pentapeptide NKISK has
      been reported to inhibit the binding of decorin, a proteoglycan on the surface of
      collagen fibrils, to fibronectin, a tissue adhesion molecule, which are thought
      to play a role in interfibrillar binding. Prior investigations have demonstrated
      that NKISK produces in vivo tendon lengthening. This study investigates the
      effect of potential clinically applicable NKISK injection regimens in an in vivo
      model. One hundred and thirteen male Sprague-Dawley rats were divided into 15
      different treatment groups, each receiving percutaneous patellar tendon
      injections of NKISK, QKTSK (a "nonsense" pentapeptide), or PBS of varying
      volumes, concentrations, and injection schedules. Following sacrifice, the
      patellar tendon lengths were measured in all groups, and biomechanical testing
      was performed with comparisons made to the contralateral, untreated control
      limbs. Tendon lengthening was significantly greater (p < or = 0.05) in nearly all
      NKISK-treated tendons as compared to PBS- and QKTSK-treated tendons and was dose
      dependent. Measured lengthening was less in rats whose sacrifice was delayed
      following the final injection of NKISK, which likely indicates recontraction of
      lengthened tendons, but they remained significantly longer than the controls.
      Biomechanical testing did not reveal significant differences in ultimate load,
      modulus, stiffness, or displacement. This study demonstrates that NKISK given in
      clinically plausible dosing regimens produces dose-dependent tendon lengthening
      in an in vivo setting with minimal effects on the mechanical properties of the
      treated tendons.

PMID- 18327808
TI  - Chemotransport contributes to the effect of oscillatory fluid flow on human bone
      marrow stromal cell proliferation.
AB  - Mechanical loads produce a diverse set of biophysical signals that may regulate
      bone cell activity, but accumulating evidence suggests that interstitial fluid
      flow is the primary signal that bone cells perceive. Because we previously
      demonstrated that oscillatory fluid flow increases human bone marrow stromal cell
      proliferation, we investigated the contribution of fluid shear stress and
      chemotransport, two stimuli induced by interstitial fluid flow. Alterations in
      flow rate at a constant peak shear stress were associated with decreases in
      oscillatory fluid flow-induced marrow stromal cell proliferation, while
      variations in peak fluid shear stress had no significant effect. Modulation of
      marrow stromal cell proliferation by flow rate may be attributed to changes in
      the release of ATP and intracellular calcium signaling. We found that if the flow
      rate is decreased while maintaining a constant peak fluid shear stress, marrow
      stromal cells release less ATP into the extracellular environment. Moreover, as
      the flow rate decreased fewer cells respond to fluid flow with an increase in
      intracellular calcium concentration. These data suggest that chemotransport is a
      prerequisite for marrow stromal cells to respond to interstitial fluid flow.

PMID- 18327809
TI  - In vivo patellar tracking: clinical motions and patellofemoral indices.
AB  - Patellar tracking during in vivo weightbearing knee function is not well
      understood. This study investigated patellar tracking of eight subjects during a
      full range of weightbearing flexion using magnetic resonance imaging and dual
      orthogonal fluoroscopy. The data were reported using a clinical description based
      on patellar and femoral joint coordinate systems and using patellar indices based
      on geometrical features of the femur and patella. The mean patellar shift was
      within 3 mm over the entire range of flexion. The patella tilted laterally from 0
      degrees to 75 degrees, and then tilted medially beyond 75 degrees of flexion. The
      mean tilt was within 6 degrees. Similarly, the mean patellar rotation was small
      at early flexion, and the mean total excursion of patellar rotation was about 8
      degrees. The patellofemoral indices showed that the mean sulcus angle and
      congruence angle varied within 8 degrees over the entire flexion range. The mean
      lateral patellar displacement was within 6 mm. A consistent decrease in lateral
      patellar tilt and an increase in lateral patellofemoral angle were observed with
      knee flexion. In conclusion, patellar motion is relatively small with respect to
      the femur during in vivo weightbearing knee flexion. These data may provide
      baseline knowledge for understanding normal patellar tracking.

PMID- 18327810
TI  - Promotion of osteogenesis in tissue-engineered bone by pre-seeding endothelial
      progenitor cells-derived endothelial cells.
AB  - In addition to a biocompatible scaffold and an osteogenic cell population, tissue
      engineered bone requires an appropriate vascular bed to overcome the obstacle of
      nutrient and oxygen transport in the 3D structure. We hypothesized that the
      addition of endothelial cells (ECs) may improve osteogenesis and prevent necrosis
      of engineered bone via effective neovascularization. Osteoblasts and ECs were
      differentiated from bone marrow of BALB/c mice, and their phenotypes were
      confirmed prior to implantation. Cylindrical porous polycaprolactone (PCL)
      hydroxyapatite (HA) scaffolds were synthesized. ECs were seeded on scaffolds
      followed by seeding of osteoblasts in the EC-OB group. In the OB group, scaffolds
      were only seeded with osteoblasts. The cell-free scaffolds were denoted as
      control group. A 0.4-cm-long segmental femur defect was established and replaced
      with the grafts. The grafts were evaluated histologically at 6 weeks
      postimplantation. In comparison with the OB group, the EC-OB group resulted in a
      widely distributed capillary network, osteoid generated by osteoblasts and absent
      ischemic necroses. Pre-seeding scaffold with ECs effectively promoted
      neovascularization in grafts, prevented the ischemic necrosis, and improved
      osteogenesis. The integration of bone marrow-derived ECs and osteoblasts in
      porous scaffold is a useful strategy to achieve engineered bone.

PMID- 18327811
TI  - Quantifying tibial plafond fracture severity: absorbed energy and fragment
      displacement agree with clinical rank ordering.
AB  - The energy of producing a fracture is considered one of the most important
      factors relating to injury severity, prognosis, and risk of complications, yet
      there has been no objective way to measure this important variable. The purpose
      of this study was to compare assessments of fracture severity made using new
      objective computed tomography (CT)-based methods versus the expert opinion of
      experienced orthopedic traumatologists. Fracture energy, fragment displacement,
      and soft tissue swelling were quantified in twenty tibial plafond fractures by
      analyzing injury CT scans. Three experienced orthopedic traumatologists then
      independently performed a rank order analysis of fracture severity, using plain
      radiographs. The concordance among the three clinicians ranged from 87% to 91%.
      Objective fracture severity measurements made with the CT algorithm agreed well
      with the clinical assessments (fracture energy concordance from 73% to 76%,
      fragment displacement from 82% to 89%, and soft tissue swelling from 61% to 65%).
      These are the first objective, CT-based measures of fracture severity. With
      further refinement, this conceptually novel method has the potential to serve as
      a valuable tool to provide objective measurement of fracture severity, allowing
      one to control for this previously confounding variable in large multicenter
      studies.

PMID- 18327812
TI  - Decreased expression of methyl methansulfonate and ultraviolet-sensitive gene
      clone 81 (Mus81) is correlated with a poor prognosis in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: Recent work has demonstrated that methyl methansulfonate and
      ultraviolet-sensitive gene clone 81 (Mus81) is critical in the maintenance of
      chromosome stability and tumor suppression in mice. To investigate its role in
      human hepatocellular carcinoma (HCC), which currently is unknown, the authors
      examined the correlation between Mus81 expression and prognosis in patients with
      HCC. METHODS: Reverse transcriptase-polymersase chain reaction and Western blot
      analyses were used to determine Mus81 expression levels in 41 paired HCC and
      paracarcinomatous liver tissue (PCLT) specimens. Immunohistochemistry analysis
      was also performed on 104 HCC specimens from patients with follow-up information.
      RESULTS: Both Mus81 messenger RNA and protein expression levels were decreased
      significantly in HCC specimens. Moreover, lower Mus81 expression levels were
      detected in nodular HCC (NHCC) than in solitary large HCC (SLHCC) specimens.
      Among 104 specimens of HCC, the positive rate of Mus81 was significantly lower
      than the rate in PCLT (P = .017), and the decreased Mus81expression was
      correlated significantly with high Edmondson-Steiner grade, multiple tumor nodes,
      and venous invasion. Patients with HCC who had low Mus81 expression had either
      poorer disease-free survival or poorer overall survival than patients who had
      with high Mus81 expression (P = .0027 and P = .0001, respectively). Multivariate
      Cox regression analysis revealed that low Mus81 expression was an independent
      prognostic factor for patients with HCC (risk ratio, 5.74; P = .012).
      CONCLUSIONS: Mus81 expression levels were decreased significantly in HCC
      specimens, and the decreased levels were correlated with a poor prognosis in
      patients with HCC, implicating Mus81 as a candidate prognostic marker in HCC.

PMID- 18327813
TI  - Randomized, placebo-controlled, pilot study evaluating aprepitant single dose
      plus palonosetron and dexamethasone for the prevention of acute and delayed
      chemotherapy-induced nausea and vomiting.
AB  - BACKGROUND: The combination of palonosetron and aprepitant is safe and effective
      in the prevention of chemotherapy-induced emesis (CIE). The purpose of this pilot
      study was to ascertain the effectiveness of 1-day versus 3-day aprepitant in the
      prevention of acute and delayed nausea and vomiting in patients who were
      receiving highly emetogenic chemotherapy. METHODS: This study was institutional
      review board-approved and informed consent was obtained before this study was
      begun. This was a pilot, single-institution, randomized, double-blind, placebo
      controlled trial that evaluated 3 different treatment arms. All groups received
      palonosetron 0.25 mg intravenously on Day 1 and dexamethasone on Days 1-4. Arm A
      received aprepitant 125 mg orally on Day 1 followed by 80 mg on Days 2-3. Arm B
      received aprepitant 125 mg orally on Day 1 and placebo on Days 2-3. Arm C
      received placebos on Days 1-3. The primary endpoint was to evaluate the
      proportion of patients with acute and delayed emesis within each group. RESULTS:
      Seventy-five patients were included in the analysis. The study commenced with 3
      groups; however, an interim analysis displayed unacceptable emesis events in Arm
      C, and this group was terminated. There were no significant differences between
      Arms A and B for emesis, nausea, or the use of breakthrough antiemetics. In Arms
      A and B, 93% of patients were emesis-free from Days 1-5 compared with only 50% in
      Arm C. CONCLUSIONS: From this pilot study of patients who were receiving
      palonosetron, aprepitant, and dexamethasone for highly emetogenic chemotherapy, a
      single dose of aprepitant displayed similar effectiveness compared with 3-day
      aprepitant.

PMID- 18327814
TI  - Nuclear factor-kappaB activation and differential expression of survivin and Bcl
      2 in human grade 2-4 astrocytomas.
AB  - BACKGROUND: Antiapoptotis resulting from hyperactivation of the transcription
      factor NF-kappaB has been described in several cancer types. It is triggered by
      the interaction of the tumor necrosis factor (TNF) with its receptors and
      recruitment of the intermediate factor TNF-receptor associated factor (TRAF) 2.
      The NF-kappaB transcriptional activity could amplify the expression of
      antiapoptotic genes. The authors investigated the activity of NF-kappaB, and the
      mRNA expression of TNFalpha, TNFalpha receptor, TRAF1, TRAF2, and TRAF-associated
      NF-kappaB activator (TANK), and the antiapoptotic genes Bcl-2, c-IAP 1 and 2, and
      Survivin in human astrocytic tumors. METHODS: Eight low-grade astrocytomas (LGA),
      10 anaplastic astrocytomas (AAs), 10 glioblastoma multiforme (GBM) samples were
      used; 4 samples of normal brain tissue were used as controls. The NF-kappaB
      activation was analyzed by electrophoretic mobility shift assay; TRAF1, TRAF2,
      TANK/I-TRAF, Bcl-2, c-IAP 1 and 2, and Survivin mRNA expressions were studied
      using real-time quantitative reverse-transcriptase polymerase chain reaction.
      RESULTS: NF-kappaB hyperactivity was detected in tumor samples. mRNA of
      antiapoptotic genes, particularly BCL-2 and Survivin, was hyperexpressed in
      gliomas. Interestingly, BCL-2 was hyperexpressed in LGAs, whereas a very high
      level of Survivin featured high-grade gliomas. The differential expression of
      antiapoptotic genes yielded a tight clustering of all LGA and nearly all GBM
      samples in cluster analysis. CONCLUSIONS: NF-kappaB and factors involved in its
      intracellular activation were up-regulated in gliomas. NF-kappaB-activated
      antiapoptotic genes were hyperexpressed in tumor samples, but showed a
      differential expression with higher levels of Bcl-2 in LGAs and higher levels of
      Survivin in GBMs.

PMID- 18327815
TI  - Editorial. Endometrioid epithelial ovarian cancer.

PMID- 18327816
TI  - Duration of testosterone suppression and the risk of death from prostate cancer
      in men treated with radiation and 6 months of hormone therapy.

PMID- 18327817
TI  - Dietary flavonoid intake and lung cancer--a population-based case-control study.
AB  - BACKGROUND: Laboratory studies suggest that flavonoids are antimutagenic and
      anticarcinogenic. To investigate the associations between commonly consumed
      flavonoid compounds and lung cancer, the authors conducted a population-based
      case-control study of 558 lung cancer cases and a group of 837 controls. METHODS:
      Dietary intakes of flavonoids were estimated by combining the intake frequency
      (collected by a food frequency questionnaire), portion size, and food composition
      data. Unconditional logistic regression analysis was used to estimate odds ratios
      (ORs) and 95% confidence limits (95% CLs) with an adjustment for potential
      confounders, including age, sex, race-ethnicity, years of schooling, smoking
      status, pack-years of tobacco smoking, and daily energy intake. RESULTS: Lung
      cancer was associated inversely with the consumption of epicatechin (in 10 mg per
      day increment: OR, 0.64; 95% CL, 0.46-0.88), catechin (4 mg per day increment:
      OR, 0.49; 95% CL, 0.35-0.70), quercetin (9 mg per day increment: OR, 0.65; 95%
      CL, 0.44-0.95), and kaempferol (2 mg per day increment: OR, 0.68; 95% CL, 0.51
      0.90) among tobacco smokers. There was little association between lung cancer and
      the flavonoid compounds mentioned above among nonsmokers. Regardless of smoking
      status, there was little association with total flavonoids: thearubigins,
      hesperetin, naringenin, and myricetin. In addition, consumption of vegetables,
      tea, and wine, all of which are rich sources of flavonoids, was associated
      inversely with lung cancer among tobacco smokers. CONCLUSIONS: Certain flavonoid
      compounds, including epicatechin, catechin, quercetin, and kaempferol, were
      associated inversely with lung cancer among tobacco smokers, but not among
      nonsmokers. Further studies of these associations may be warranted.

PMID- 18327818
TI  - Role of resection margins in patients treated with breast conservation surgery.
AB  - BACKGROUND: After breast conservation therapy (BCT), margin status is routinely
      evaluated to select patients who need reexcision. The aim of this study was to
      investigate how margin status and other clinicopathologic factors correlate with
      the presence of residual tumor at reexcision. METHODS: A series of 431 breast
      cancer patients who underwent BCT followed by reexcision were considered because
      they had positive or close (< or =3 mm) margins. At univariate and multivariate
      analysis the frequency of residual tumor in the reexcision specimens was
      associated with the status and width of resection margins and with a series of
      other clinicopathologic factors. RESULTS: Of the 382 evaluable patients, 253 had
      positive and 129 close margins. Residual tumor was found at reexcision in 51.8%
      positive-margin patients and 34.1% close-margin patients (P = .001). In the
      latter group tumor-margin distance (range, 0.08 to 3 mm) was not associated with
      the incidence of residual tumor (P = .134). On univariate analysis age < or =45
      years (P = .006), intraductal histotype (P = .005), size > 2 cm (P = .010),
      positive axillary nodes (P = .031), and timing of reexcision (P = .044) were
      significantly associated with a higher frequency of residual tumor. All these
      factors, except tumor size, maintained a significant predictive value on
      multivariate analysis. CONCLUSIONS: In the presence of positive margins, relevant
      residual disease cannot be ruled out and further surgery is indicated. Close
      margins do not mandate reexcision because they may indicate either that the tumor
      has been radically excised or the presence of residual foci of a multifocal
      tumor, which are usually effectively treated by radiotherapy.

PMID- 18327819
TI  - Epithelial to mesenchymal transition in head and neck squamous carcinoma:
      association of Src activation with E-cadherin down-regulation, vimentin
      expression, and aggressive tumor features.
AB  - BACKGROUND: Epithelial-mesenchymal transformations (EMT) are critical for the
      invasion, progression, and metastasis of epithelial carcinogenesis. The role of
      EMT in head and neck squamous carcinoma (HNSC) tumorigenesis remains unexplored.
      In the current study, the expressions of several factors associated with the
      induction of EMT in HNSC cell lines and tumor specimens were investigated to
      define their functional and pathologic role in HNSC. METHODS: Eleven HNSC cell
      lines and 50 primary tumor tissue specimens formed the materials of this study.
      Western blot analysis as well as immunohistochemical, and functional techniques
      were used to assess the status of activated Src (p-Src), E-cadherin, and vimentin
      in both cell lines and tumor tissues and the results were correlated with
      patients' clinicopathologic parameters. RESULTS: The results demonstrated the
      inverse expression of p-Src and E-cadherin in the majority of cell lines and in
      primary tumor tissues compared with normal squamous mucosa. Elevated levels of p
      Src were accompanied by down-regulation of E-cadherin and the expression of
      vimentin in epithelial tumor cells. In vitro inhibition of Src led to E-cadherin
      reexpression and increased cell contact in squamous carcinoma cell lines.
      Immunophenotypic analysis of these markers in primary tumor tissues demonstrated
      a significant correlation between increased p-Src, decreased E-cadherin, and
      vimentin expression and aggressive tumor features including penetrating invasive
      fronts, high-grade sarcomatoid transformation, and lymph node metastasis.
      CONCLUSIONS: The results of the current study indicate that Src and E-cadherin
      may play an important role in EMT, invasion, and aggressive clinicopathologic
      features of HNSC. These proteins may be targeted for the therapeutic intervention
      of patients with HNSC.

PMID- 18327820
TI  - Treatment with bevacizumab and irinotecan for recurrent high-grade glial tumors.
AB  - BACKGROUND: Response rates to second-line chemotherapy in recurrent high-grade
      glial tumors are low and new effective treatments are needed. The objective of
      this study was to evaluate response rates and tolerability of chemotherapy with
      bevacizumab and irinotecan in recurrent high-grade gliomas. METHODS: Twenty
      patients with recurrent gliomas were treated with bevacizumab 5 mg/kg and
      irinotecan 125 mg/m(2) every 2 weeks. The response was evaluated by gadolinium
      enhanced magnetic resonance imaging performed every 4 cycles of treatment.
      RESULTS: The patients received 1 to 22 cycles of treatment. Nine of 19 patients
      available for response evaluation (47.3%) showed an objective radiologic
      response: 2 patients (10.5%) a complete response (CR), and 7 patients (36.8%) a
      partial response (PR). Two additional patients showed stable disease (SD) for 2
      and 6 months, respectively. Eight patients developed rapid progression after 1 to
      4 cycles of treatment. Median time to progression on treatment was 4.7 months.
      The 6-month progression-free survival (PFS) and overall survival (OS) were 25%
      and 55%, respectively. The adverse effects were mild and in all but 2 cases were
      no more than grade 2. There were no thrombotic complications or significant
      bleeding other than epistaxis. CONCLUSIONS: The preliminary data show a promising
      high response rate of recurrent high-grade gliomas to chemotherapy with
      bevacizumab and irinotecan. The regimen is associated with minimal toxicity.

PMID- 18327822
TI  - Renal sparing surgery for children with bilateral Wilms tumor.

PMID- 18327824
TI  - Structural brain abnormalities in psychopaths-a review.
AB  - The biological basis of psychopathy has not yet been fully elucidated. Few
      studies deal with structural neuroimaging in psychopaths. The aim of this article
      is to review these studies in order to contribute to our understanding of the
      biological basis of psychopathy. Data in the literature report a reduction in
      prefrontal gray matter volume, gray matter loss in the right superior temporal
      gyrus, amygdala volume loss, a decrease in posterior hippocampal volume, an
      exaggerated structural hippocampal asymmetry, and an increase in callosal white
      matter volume in psychopathic individuals. These findings suggest that
      psychopathy is associated with brain abnormalities in a prefrontal-temporo-limbic
      circuit-i.e. regions that are involved, among others, in emotional and learning
      processes. Additionally, data indicate that psychopathic individuals cannot be
      seen as a homogeneous group. The associations between structural changes and
      psychopathic characteristics do not enable causal conclusions to be drawn, but
      point rather to the important role of biological brain abnormalities in
      psychopathy. To gain a comprehensive understanding of this, psychopathy must be
      viewed as a multifactorial process involving neurobiological, genetic,
      epidemiological and sociobiographical factors.

PMID- 18327823
TI  - Twenty years of follow-up among survivors of childhood and young adult acute
      myeloid leukemia: a report from the Childhood Cancer Survivor Study.
AB  - BACKGROUND: Limited data exist on the comprehensive assessment of late medical
      and social effects experienced by survivors of childhood and young adult acute
      myeloid leukemia (AML). METHODS: This analysis included 272 5-year AML survivors
      who participated in the Childhood Cancer Survivor Study (CCSS). All patients were
      diagnosed at age < or =21 years between the years 1970 and 1986, and none
      underwent stem cell transplantation. Rates of survival, relapse, and late
      outcomes were analyzed. RESULTS: The average follow-up was 20.5 years (range, 5
      33 years). The overall survival rate was 97% at 10 years (95% confidence interval
      [95%CI], 94%-98%) and 94% at 20 years (95% CI, 90%-96%). Six survivors reported 8
      recurrences. The cumulative incidence of recurrent AML was 6.6% at 10 years (95%
      CI, 3.7%-9.6%) and 8.6% at 20 years (95% CI, 5.1%-12.1%). Ten subsequent
      malignant neoplasms (SMN) were reported, including 4 with a history of radiation
      therapy, for a 20-year cumulative incidence of 1.7% (95% CI, 0.02%-3.4%). Six
      cardiac events were reported, for a 20-year cumulative incidence 4.7% (95% CI,
      2.1%-7.3%). Half of the survivors reported a chronic medical condition and,
      compared with siblings, were at increased risk for severe or life-threatening
      chronic medical conditions (16% vs 5.8%; P < .001). Among those aged > or =25
      years, the age-adjusted marriage rates were similar among survivors and the
      general United States population (57% for both) and lower compared with siblings
      (67%; P < .01). Survivors' college graduation rates were lower compared with
      siblings but higher than the general population (40% vs 52% vs 34%, respectively;
      P < .01). Employment rates were similar between survivors, siblings, and the
      general population (93%, 97.6%, and 95.8%, respectively). CONCLUSIONS: Long-term
      survival from childhood AML > or =5-years after diagnosis was favorable. Late
      occurring medical events remained a concern with socioeconomic achievement lower
      than expected within the individual family unit, although it was not different
      from the general United States population.

PMID- 18327825
TI  - Introduction to this issue: international perspectives on brain imaging and the
      law.

PMID- 18327826
TI  - Disturbed prefrontal and temporal brain function during emotion and cognition
      interaction in criminal psychopathy.
AB  - Impaired emotional responsiveness has been revealed as a hallmark of psychopathy.
      In spite of an increasing database on emotion processing, studies on cognitive
      function and in particular on the impact of emotion on cognition in psychopathy
      are rare. We used pictures from the International Affective Picture Set (IAPS)
      and a Simon Paradigm to address emotion-cognition interaction while functional
      and structural imaging data were obtained in 12 healthy controls and 10
      psychopaths. We found an impaired emotion-cognition interaction in psychopaths
      that correlated with a changed prefrontal and temporal brain activation. With
      regard to the temporal cortex, it is shown that structure and function of the
      right superior temporal gyrus is disturbed in psychopathy, supporting a
      neurobiological approach to psychopathy, in which structure and function of the
      right STG may be important.

PMID- 18327827
TI  - Neurophilosophical perspectives of neuroimaging in forensic psychiatry-giving way
      to a paradigm shift?
AB  - Forensic psychiatry is concerned with the relationship between psychiatric
      abnormalities and legal violations and crimes. Due to the lack of available
      biological criteria, evaluation and therapy in forensic psychiatry have so far
      been restricted to psychosocial and mental criteria of offenders' personalities.
      Recent advances in neurosciences allow a closer approach to the neural correlates
      of personality, moral judgments and decision-making. We propose to discuss the
      introduction of biological criteria in the field of forensic psychiatry and to
      establish rules as to what extent such biological criteria will be a better and
      more reliable choice in judging mentally ill criminals by using all available
      information that can be obtained by biological means. Psychosocial and subjective
      criteria in forensic evaluation will be more and more accomplished by
      biopsychosocial and objective criteria. The responsibility of having committed a
      criminal act will no longer be exclusively defined by judging free and voluntary
      decision-making, but rather by brain-behavior relationships. What is often
      referred to as psychosocially determined mental processes thus could be
      complemented by estimating the degree of biopsychosocially determined neural
      processes. We conclude that such a process could contribute to a paradigm shift
      in forensic psychiatry, which will have profound implications for offenders,
      forensic psychologists and psychiatrists, the law and society in general.

PMID- 18327828
TI  - Structural and functional MRI- findings in children and adolescents with
      antisocial behavior.
AB  - BACKGROUND: The developmental course of children with conduct disorder (CD) is
      heterogeneous. Especially children who exhibit symptoms early in their lifetimes
      are characterized by a negative outcome. Neurobiological aspects of CD have been
      investigated in these children but little is known about structural and
      functional brain aberrations. METHODS: We describe the developmental taxonomy of
      children with CD and focus on those with the early onset subtype. Structural MRI
      data of these children and antisocial adults are recapitulated. The impact of
      investigating neurobiological underpinnings of antisocial behavior and how this
      might contribute to future forensic and psychiatric assessments is discussed.
      RESULTS/ CONCLUSION: Children display similar structural aberrations of fronto
      limbic structures to adults with antisocial behavior, and amygdala dysfunction
      might be closely related to dysregulated emotions. Though the investigation of
      biological factors in antisocial subjects has made great progress in recent
      years, today MRI is still a rather complex, expensive and indistinct method for
      forensic assessment.

PMID- 18327829
TI  - The effects of neuroimaging and brain injury on insanity defenses.
AB  - Although neurological evidence is used with increasing frequency in criminal
      trials, there is limited research examining the effects that this evidence has on
      juror decision-making in insanity trials. Participants (396) were presented with
      a case summary and psychological testimony and asked to render either a verdict
      of guilty or not guilty by reason of insanity in a 2 (psychosis or psychopathy) x
      (presence or absence of an MRI indicating a brain lesion) x (presence or absence
      of testimony describing a car accident that caused injury to the brain) factorial
      design. Defendants diagnosed with a psychotic disorder, defendants who could
      demonstrate the existence of a brain lesion via MRI, and defendants who had a
      history of brain injury were more likely to be found not guilty by reason of
      insanity than those defendants who did not present any neurological testimony.
      Participants who reported they were more influenced by the psychological and
      neurological testimony were almost six times more likely to render a verdict of
      NGRI than those participants who reported that the psychological and neurological
      testimony and evidence did not influence their decision regarding verdict.

PMID- 18327830
TI  - Flickering admissibility: neuroimaging evidence in the U.S. courts.
AB  - This article explores the admissibility of neuroimaging evidence in U.S. courts,
      recognizing various trends in decisions about such evidence.While courts have
      routinely admitted some neuroimages, such as CT scans and MRI, as proof of trauma
      and disease, they have been more circumspect about admitting the PET and SPECT
      scans and fMRI evidence. With the latter technologies, courts have often
      expressed reservations about what can be inferred from the images. Moreover,
      courts seem unwilling to find neuroimaging sufficient to prove either insanity or
      incompetency, but are relatively lenient about admitting neuroimages in death
      penalty hearings. Some claim that fMRI and "brain fingerprinting" are able to
      detect deception. Other scholars argue that brain fingerprinting is a dubious
      concept and that fMRI is not yet sufficiently reliable. Moreover, there are
      substantial concerns about privacy and the perils of mind reading implicit in
      such technology. Yet, there is a movement to try to make these new technologies
      "courtroom ready" in the near future, raising a host of legal, policy, and
      ethical questions to be answered.

PMID- 18327831
TI  - Brain abnormalities in antisocial individuals: implications for the law.
AB  - With the increasing popularity in the use of brain imaging on antisocial
      individuals, an increasing number of brain imaging studies have revealed
      structural and functional impairments in antisocial, psychopathic, and violent
      individuals. This review summarizes key findings from brain imaging studies on
      antisocial/aggressive behavior. Key regions commonly found to be impaired in
      antisocial populations include the prefrontal cortex (particularly orbitofrontal
      and dorsolateral prefrontal cortex), superior temporal gyrus, amygdala
      hippocampal complex, and anterior cingulate cortex. Key functions of these
      regions are reviewed to provide a better understanding on how deficits in these
      regions may predispose to antisocial behavior. Objections to the use of imaging
      findings in a legal context are outlined, and alternative perspectives raised. It
      is argued that brain dysfunction is a risk factor for antisocial behavior and
      that it is likely that imaging will play an increasing (albeit limited) role in
      legal decision-making.

PMID- 18327832
TI  - Neural correlates of deficient response inhibition in mentally disordered violent
      individuals.
AB  - In this study, response inhibition and associated neural activation during a
      motor inhibition paradigm were investigated in (i) men with antisocial
      personality disorder (APD) with a history of violence (n = 14), (ii) men with
      schizophrenia with a history of violence (n = 12), (iii) men with schizophrenia
      without a history of violence (n = 12), and (iv) healthy control subjects (n =
      14) using functional magnetic resonance imaging (fMRI). At the behavioural level,
      individuals with schizophrenia showed impaired performance across all conditions,
      whereas an increased error rate was seen in the APD group only during the
      conditions requiring inhibition. At the neural level, both violent groups showed
      reduced thalamic activity, compared with controls, in association with modulation
      of inhibition by task demands. In addition, the violent schizophrenia group,
      compared with controls, showed reduced activity in the caudate nucleus during the
      condition requiring inhibition. It is concluded that violence may not be
      specifically associated with impaired voluntary inhibition in schizophrenia but
      this is likely in APD. Reduced thalamic function, perhaps due to its known
      association with sensorimotor disturbances, is implicated in violent behaviour
      across both disorders. In addition, caudate dysfunction may contribute, given its
      role in timing and temporal processing as well as suppression of motor actions,
      to deficient inhibition and violent behaviour in schizophrenia.

PMID- 18327833
TI  - Which is the most appropriate stenting technique with drug-eluting stent for
      unprotected left main bifurcation stenosis?

PMID- 18327834
TI  - Is a rose just a rose?: comment on the classification of coronary artery
      bifurcation lesions and treatments: time for a consensus!-article by Louvard et
      al.

PMID- 18327835
TI  - Outcome of intracoronary stenting after failed maximal medical therapy in
      patients with symptomatic myocardial bridge.
AB  - OBJECTIVES: The aim of the present study was to study the outcome of coronary
      stenting in patients with symptomatic myocardial bridging refractory to standard
      medical therapy. BACKGROUND: Medical therapy constitutes the first line treatment
      for patients with symptomatic myocardial bridge, surgical correction may be
      offered to select patients with refractory symptoms. Limited data exists on the
      outcome of coronary stenting in this patient cohort. METHODS: Twenty-nine
      patients with symptoms of angina, documented myocardial ischemia and
      angiographically documented myocardial bridge of the left anterior descending
      artery (defined as [mt]50% systolic compression) were identified retrospectively.
      Seventeen (59%) patients responded to maximized medical therapy (mean age 51 +/-
      16 years, range 29-80, 7 female) and 12 (41%) patients received coronary stents
      following a failed attempt of minimum 3 months of maximal medical therapy (mean
      age 49 +/- 15 years, range 32-76 years, 5 females). Medical therapy responders
      were compared with intracoronary stent group for recurrent severe angina, target
      vessel revascularization (TVR), myocardial infarction (MI), and death at follow
      up. RESULTS: Intracoronary stents were placed in all patients successfully. The
      incidence of recurrent severe angina and TVR were significantly greater in the
      stent group (P = 0.04) while MI and death in two groups were similar at mean
      follow-up of 15 +/- 3 months. CONCLUSIONS: Coronary stent placement for medically
      refractory symptomatic myocardial bridge failed to relieve severe angina and is
      associated with high clinical restenosis and hence should be avoided.

PMID- 18327836
TI  - Stent fracture following stenting of a myocardial bridge: report of two cases.
AB  - Myocardial bridge is the most common congenital coronary anomaly. Patients with
      this anomaly are usually asymptomatic, but it may cause myocardial ischemia that
      may lead to myocardial infarction. Treatment for myocardial bridge remains
      controversial. Current recommendations include medical therapy, surgical
      treatment (unroofing myotomy), coronary artery bypass, and percutaneous coronary
      stenting. We report two cases of stent fracture following stenting of a
      myocardial bridge. The risk of stent fracture leading to restenosis and/or stent
      thrombosis should be considered when assessing the risks and benefits of coronary
      revascularization of a myocardial bridge.

PMID- 18327837
TI  - Stenting LAD myocardial bridges: is the glass half empty or...

PMID- 18327838
TI  - Pharmacological options for inducing maximal hyperaemia during studies of
      coronary physiology.
AB  - The coronary pressure wire is used for physiological assessment of the coronary
      vasculature increasingly frequently in clinical practice. Fractional flow reserve
      (FFR) can now be used to assess lesion severity in a variety of anatomical
      situations. Increasingly, the coronary pressure wire is being used to interrogate
      the coronary microvasculature. Coronary flow reserve (CFR) and Index of
      microcirculatory resistance (IMR) require hyperaemia to accurately assess
      thermodilution-derived mean transit times, and pressure derived collateral flow
      index (CFIp) is calculated from coronary wedge pressure and aortic pressure at
      hyperaemia. In addition, coronary flow velocity as assessed by a coronary Doppler
      flow wire needs appropriate induction of hyperaemia. However, the majority of
      this article will however focus on hyperaemia induction for pressure wire studies
      particularly FFR. Significant clinical decisions are made as a result of FFR
      readings, therefore it is imperative that they are carried out correctly. Maximal
      coronary hyperaemia is essential in producing accurate, reproducible
      measurements. This article focuses on the pharmacological agents that can be used
      for this purpose, discusses which agents can be used in specific situations, and
      briefly addresses the future of pharmacological stress in the catheter
      laboratory.

PMID- 18327839
TI  - Advances in diagnosis and treatment in patients with pulmonary arterial
      hypertension.
AB  - Pulmonary arterial hypertension (PAH) is a progressive disease marked by
      vasoconstriction and vascular remodeling within pulmonary arteries leading to
      right heart failure and death. Significant advances in understanding the
      pathobiology of the disease have identified three key pathways involved in
      progression of this disease, which are the endothelin pathway, the prostacyclin
      pathway, and the nitric oxide/cyclic guanosine monophosphate pathway.
      Echocardiogram is the best screening tool to obtain an estimation of the
      pulmonary artery systolic pressure but right heart catheterization remains the
      standard by which the diagnosis is made. There are currently six FDA approved
      therapies for PAH. The mechanistic rationale, evidence behind their use and side
      effect considerations in utilizing these therapies in PAH patients will be the
      focus of this review.

PMID- 18327840
TI  - Balloon assessment of patent foramen ovale morphology and the modification of
      tunnels using a balloon detunnelisation technique.
AB  - OBJECTIVES: (1) To define patent foramen ovale (PFO) morphology using balloon
      assessment and identify those with long tunnel type morphology. (2) To describe a
      novel technique of detunnelisation to facilitate PFO device closure in patients
      with long tunnel PFO morphology. BACKGROUND: An appreciation that PFO morphology
      varies from simple defects through to long tunnel-like defects is important for
      their successful transcatheter closure. Using standard closure techniques for
      long tunnels can be problematic. METHODS: Consecutive patients who underwent
      transcatheter PFO closure from April 1, 2005 to March 31, 2006 had assessment of
      PFO morphology using a compliant sizing balloon. The sites of constraint of the
      balloon allowed identification of the PFO entrance, exit, and length. The PFO was
      classified as being a long tunnel when the length was greater than the diameter
      of either the entrance or exit. Those with a long tunnel had detunnelisation
      performed and the defect was then closed. RESULTS: 44 patients (32 females), mean
      age 50 years were studied. On balloon assessment 10 (23%) met the criteria for
      long tunnels. Detunnelisation allowed successful closure with the STARFlex (NMT
      Medical, Boston, MA) device in 9 of 10 patients. In the other case transseptal
      puncture was required after detunnelisation before closure. CONCLUSIONS: Balloon
      assessment of PFOs enhances the understanding of their morphology and aids the
      identification of long tunnels. Detunnelisation using the same balloon
      facilitates the uncomplicated transcatheter closure of long tunnel PFOs in most
      patients.

PMID- 18327841
TI  - PFO anatomy: 3D characterization and device performance.

PMID- 18327842
TI  - Use of Amplatzer occlusion devices to occlude Fontan baffle leaks during
      fenestration closure procedures.
AB  - The authors describe the use of Amplatzer occlusion devices to successfully
      occlude Fontan baffle leaks in three patients. These additional right to left
      shunts were recognized at the time of elective transcatheter closure of
      surgically created fenestrations. A common site of baffle leak is described at
      the base of the right atrial appendage. This suture line serves to exclude the
      right atrial appendage from Fontan baffle flow and lies within the corrugated
      surface of the pectinate muscles, making it particularly vunerable to baffle
      leaks over time.

PMID- 18327843
TI  - Cutting balloon angioplasty for resistant venous stenoses of dialysis access:
      immediate and patency results.
AB  - OBJECTIVES: To evaluate the technical success, safety and patency of cutting
      balloon angioplasty for the treatment of resistant dialysis access stenoses.
      BACKGROUND: Cutting balloon angioplasty has been proposed to be useful in
      treating resistant dialysis access stenoses. However, they are based on
      experience with very limited cases and formal patency data is insufficient.
      METHODS: The author retrospectively reviewed 896 percutaneous transluminal
      angioplasty (PTA) procedures for the treatment of dysfunctional or thrombotic
      dialysis access. Thirty-seven of 623 patients with native fistulas and 23 of 273
      patients with synthetic grafts had residual stenoses of more than 30% after
      conventional PTA at an inflation pressure of 24 atm for 60 sec. In these 60
      patients, additional cutting balloon PTA was performed. RESULTS: The overall
      technical success rate was 96.7% and clinical success rate was 98.3%. Only one
      patient experienced mild local extravasation. The postintervention primary
      patency rates for native fistula group (N = 37) were 100%, 86.4%, and 67.5% at 1
      month, 3-month, and 6-month; the postintervention primary patency rates for
      synthetic graft group (N = 23) were 87.0%, 60.9%, and 34.2% at 1-month, 3-month,
      and 6-month respectively. CONCLUSIONS: For resistant venous stenoses of dialysis
      access, cutting balloon PTA is effective, safe, and seems to provide comparative
      primary patency as suggested by guidelines.

PMID- 18327844
TI  - Cutting balloon angioplasty: is it the key to access?

PMID- 18327845
TI  - Lengthening of proximal implantation site during endovascular repair of thoracic
      aortic aneurysm: preservation of carotid patency with retrograde trans endograft
      deployment of a carotid stent.
AB  - Endovascular repair of descending thoracic aortic aneurysms with a reduced
      proximal implantation site represents a technical challenge. Surgical procedures
      before endovascular exclusion can be necessary to increase the length of the
      proximal landing site to avoid type 1 endoleaks. We present a case of
      endovascular exclusion of a descending thoracic aortic aneurysm with the
      endograft placed proximal to the left common carotid artery. Flow to this arch
      was preserved reconstructing the carotid ostium with the retrograde implantation
      of a carotid stent that was placed extending across an orifice created in the
      deployed endograft by puncture and balloon dilatation.

PMID- 18327846
TI  - Renal artery stenting with two simultaneous protection devices.
AB  - PURPOSE: To describe a new technique for distal protection during stenting of a
      bifurcated renal artery using two simultaneous filter devices. CASE REPORT: A 70
      year-old patient underwent angiography of a single functional kidney. Severe
      proximal, nonostial narrowing of an early bifurcated renal artery was found. Two
      AngioGuard filter protection devices were placed, one in each branch. A balloon
      mounted stent was advanced over both wires simultaneously till they reached
      divergence point, expanded fully, and the protection devices were retrieved. No
      complications were observed and the final result was good. CONCLUSION: The
      concomitant use of two protection devices is feasible in a particular anatomy
      context.

PMID- 18327847
TI  - "Trans-collateral" angioplasty for a challenging chronic total occlusion of the
      tibial vessels: a novel approach to percutaneous revascularization in critical
      lower limb ischemia.
AB  - Arterial revascularization by means of percutaneous transluminal angioplasty
      (PTA) is a mainstay in the management of patients with peripheral artery disease
      and critical limb ischemia (CLI). However, when employing standard approaches,
      PTA of below-the-knee arteries may fail in up to 20% of cases. In the present
      article, we report a novel interventional strategy, the "transcollateral"
      angioplasty approach, which we successfully employed in a patient with critical
      lower limb ischemia and a challenging total infrapopliteal occlusion. This
      technique may probably increase success rates of PTA in very challenging total
      occlusions of below-the-knee arteries (e.g., those lacking a proximal occlusion
      stump). The tips pertinent to this case are illustrated, including the need to
      accurately choose appropriate guidewires and balloons, and the identification of
      the most appropriate collateral pathway.

PMID- 18327848
TI  - Determination of pentachlorophenol and tribromophenol in sawdust by ultrasound
      assisted extraction and MEKC.
AB  - An ultrasonic bar-assisted extraction and CE separation procedure for the
      determination of pentachlorophenol (PCP) and 2,4,6-tribromophenol (TBP) residues
      in sawdust was developed and applied. For this purpose, micellar electrokinetic
      capillary chromatography (MEKC) was used and compared with a GC/MS methodology.
      This methodology allowed the quantification of PCP and TBP in a concentration
      range of 2.5-12.0 mg/kg for TBP and 2.8-12.0 mg/kg for PCP. Different sample
      treatment processes were evaluated in order to extract these compounds from
      sawdust. Better results were obtained when the residues were extracted with
      ultrasound-assisted hexane, filtered, evaporated, dissolved in Na(2)CO(3), and
      injected into the CE equipment. The optimal option for GC/MS was extraction with
      Na(2)CO(3 )followed by a derivation using acetic anhydride and liquid-liquid
      extraction with hexane. This method allowed the quantification of TBP and PCP in
      sawdust in a concentration range of 0.19-12.00 mg/kg and 0.14-12.00 mg/kg,
      respectively. The CE method was compared with the GC/MS as reference method. The
      results were shown to be statistically similar by both methods for PCP as well as
      for TBP.

PMID- 18327849
TI  - Alkannin/shikonin mixture from roots of Onosma echioides (L.) L.: extraction
      method study and quantification.
AB  - This work reports the extraction procedures of alkannin/shikonin mixture from
      roots of six populations of Onosma echioides, by means of three extraction
      techniques: Soxhlet extraction, maceration and rapid solid-liquid dynamic
      extraction (RSLDE). Five solvents with different polarity (hexane, petroleum
      ether, chloroform, ethyl acetate, methanol) were also studied. Analysis of the
      extracts was performed by an HPLC-DAD (diode array detector) system. The most
      efficient extraction technique was Soxhlet procedure using ethyl acetate for 6 h.
      Studied samples of O. echioides showed an alkannin/shikonin content in the range
      of 0.02-0.24 mg/kg. Other naphthoquinone derivatives (deoxyalkannin/deoxyshikonin
      and 5,8-dihydroxy-2-(4-methyl-6-oxo-5,6-dihydro-2H-pyran-2-yl)
      [1,4]naphthoquinone and arnebin-6) were found for the first time in O. echioides
      and characterized in the extracts using HPLC-MS apparatus equipped with an ESI
      ionization source.

PMID- 18327850
TI  - The effect of cold trap adsorbents on the gas chromatographic analysis of ambient
      VOCs under Peltier cooling conditions.
AB  - In this work, the relative analytical performance of the GC-based detection
      method was investigated with a major focus on cold trap (CT) adsorbent materials
      against four aromatic volatile organic compounds (VOCs) (e. g., benzene, toluene,
      xylene, and styrene). A series of calibration experiments were hence conducted
      under cryofocusing conditions formed by the Peltier cooling system in a thermal
      desorber (TD) unit. During the course of this study, comparative calibration
      datasets were acquired for each of the three CT types: (i) CT (I) = Carbopack B +
      Carbopack C, (ii) CT (II) = Carbopack B + Carboxen 1000, and (iii) CT (III) =
      Tenax TA. All calibration datasets were obtained under subambient temperature (
      10 degrees C) conditions controlled by the Peltier cooling system. The
      reliability of the calibration data was also assessed in an ancillary experiment
      with the aid of the modified injection through a thermal desorber (MITD) method.
      The results demonstrated that the GC detection properties of different VOCs were
      not altered significantly between different CT applications under Peltier
      conditions, although relative sensitivity could be distinguished moderately
      depending on the CT type.

PMID- 18327851
TI  - Development of a polymer-coated stationary phase with improved chemical stability
      in alkaline mobile phases.
AB  - An endcapped stationary phase is prepared by thermal immobilization of
      poly(methyltetradecylsiloxane) (PMTDS) onto a doubly zirconized silica support
      followed by endcapping using a mixture of hexamethyldisilazane and
      trimethylchlorosilane. The preparation of the Si-Zr(PMTDS)ec phase shows good
      repeatability with RSD <3.0% for carbon loadings and column efficiency. This new
      stationary phase has a lower density of residual hydroxyl groups, according to
      spectroscopic methods while basic compounds from the Tanaka and Engelhardt test
      mixtures are eluted with essentially symmetric peaks. Furthermore, the stability
      of the Si-Zr(PMTDS)ec stationary phase, measured using an accelerated aging test,
      is twice as great as the stability of a similar nonendcapped phase. The new phase
      shows promise for the separation of basic pharmaceuticals.

PMID- 18327852
TI  - Replicated studies of two randomized trials of angiotensin-converting enzyme
      inhibitors: further empiric validation of the 'prior event rate ratio' to adjust
      for unmeasured confounding by indication.
AB  - PURPOSE: Using data from the United Kingdom General Practice Research Database
      (GPRD) randomized controlled trials (RCTs) were replicated to determine whether
      identifiable study characteristics and/or analytic methods influence the validity
      of observational studies. METHODS: This study reports GPRD replications of 2 RCTs
      that investigated whether angiotensin-converting enzyme inhibitors (ACEIs)
      improve cardiovascular outcomes in patients without congestive heart failure at
      high risk for cardiovascular disease (heart outcomes prevention evaluation (HOPE)
      and EUROPA). The GPRD studies replicated to the extent feasible all aspects of
      these RCTs except for randomization. RESULTS: With adjustment for confounders
      using conventional biostatistical techniques, both GPRD studies exhibited results
      divergent from the RCTs. Myocardial infarction, stroke, congestive heart failure,
      and coronary revascularization were increased in the Exposed group of both GPRD
      studies; whereas these outcomes either were decreased or unchanged by ACEI
      therapy in both RCTs. The results also were analyzed with a new method that
      appears to adjust for both identified and unmeasured confounders. With this
      methodology that employs the ratio of event rates between the Exposed and
      Unexposed cohorts prior to study start time to adjust the study hazard ratio
      (HR), the GPRD results for myocardial infarction, stroke, and coronary
      revascularization were largely similar to those found in the two RCTs.
      CONCLUSIONS: This study provides additional empiric evidence suggesting that this
      new analytic methodology, 'prior events rate ratio (PERR)' adjustment, is a
      promising solution for the vexing problem of 'unmeasured confounding' in
      observational studies. Additional statistical simulations are needed to fully
      appreciate the applicability and limitations of this method.

PMID- 18327853
TI  - An aviation perspective of safety in the pharmaceutical sector.

PMID- 18327854
TI  - Ion internal energy distributions validate the charge residue model for small
      molecule ion formation by spray methods.
AB  - This paper reports a detailed study of the internal energy distribution of ions
      formed by four electrospray ionization (ESI)-related ionization methods, with
      particular emphasis on electrosonic spray ionization (ESSI). Substituted
      benzylpyridinium ions were used as thermometer ions to probe the internal energy
      distribution. The influence of different instrumental parameters was studied.
      Cone and skimmer voltages as well as the collision energy were found to strongly
      affect the ion internal energy distribution, whereas the distance between the
      emitter and the inlet of the mass spectrometer, the nebulizing gas pressure or
      the flow rate showed no influence. The internal energy distribution obtained with
      an ESSI source was compared with those obtained for electrospray (ESI),
      nanoelectrospray (nanoESI) and sonic spray ionization (SSI) on the same mass
      spectrometer with the same instrumental parameters. No clear differences were
      observed. As the charge residue model is the only ion formation mechanism
      possible for SSI, we conclude that benzylpyridinium ions are formed by the
      pathway suggested by this model.

PMID- 18327855
TI  - High-throughput, accurate mass liquid chromatography/tandem mass spectrometry on
      a quadrupole time-of-flight system as a 'first-line' approach for metabolite
      identification studies.
AB  - Throughput for drug metabolite identification studies has been increased
      significantly by the combined use of accurate mass liquid chromatography/tandem
      mass spectrometry (LC/MS/MS) data on a quadrupole time-of-flight (QTOF) system
      and targeted data analysis procedures. Employed in concert, these tools have led
      to the implementation of a semi-automated high-throughput metabolite
      identification strategy that has been incorporated successfully into lead
      optimization efforts in drug discovery. The availability of elemental composition
      data on precursor and all fragment ions in each spectrum has greatly enhanced
      confidence in ion structure assignments, while computer-based algorithms for
      defining sites of biotransformation based upon mass shifts of diagnostic fragment
      ions have facilitated identification of positions of metabolic transformation in
      drug candidates. Adoption of this technology as the 'first-line' approach for in
      vitro metabolite profiling has resulted in the analysis of as many as 21 new
      chemical entities on one day from diverse structural classes and therapeutic
      programs.

PMID- 18327856
TI  - A comparison of carbon and nitrogen stable isotope ratios of fish tissues
      following lipid extractions with non-polar and traditional chloroform/methanol
      solvent systems.
AB  - Stable isotope ratios act as chemical tracers of animal diet, and are used to
      study food web dynamics. Because carbon stable isotope values are influenced by
      tissue lipid content, a number of extraction methods have been used to remove
      lipid bias, but, in some species and tissues, extractions also alter nitrogen
      isotope values. We have analyzed delta(13)C and delta(15)N in Atlantic bluefin
      tuna liver and white muscle, and whole Atlantic herring, fish tissues covering a
      wide range of lipid content (bulk C:N 3.1-12.5). In order to compare delta(13)C
      and delta(15)N values from traditional chloroform/methanol extractions with non
      polar solvent alternatives, we analyzed samples following (1) no treatment, (2)
      lipid removal using chloroform/methanol (2:1), and (3) Soxhlet extractions using
      chloroform, diethyl ether or hexane. Chloroform/methanol and chloroform
      extractions produced the lowest C:N values and highest delta(13)C values. In
      bluefin tuna, chloroform and hexane extractions significantly altered liver
      delta(15)N, and all methods significantly altered delta(15)N values in white
      muscle. Whole Atlantic herring delta(15)N was not altered by any extraction
      method, while the 2:1 chloroform/methanol extraction most completely removed fish
      tissue lipid components. Our results indicate that delta(15)N effects are not
      limited to common chloroform/methanol extractions and suggest that
      chloroform/methanol is the most effective extraction for delta(13)C correction.
      Given evidence for delta(15)N alteration among all tested methods, mathematical
      correction approaches should be further explored as an alternative to lipid
      correction.

PMID- 18327857
TI  - Replication of the Scandinavian Simvastatin Survival Study using a primary care
      medical record database prompted exploration of a new method to address
      unmeasured confounding.
AB  - PURPOSE: To examine whether identifiable study characteristics and/or analytic
      methods used determine observational study validity, as assessed by replicating
      randomized controlled trials using observational data. METHODS: A cohort from the
      United Kingdom General Practice Research Database (GPRD) was used to replicate
      the Scandinavian Simvastatin Survival Study RCT, which investigated statin
      treatment of hypercholesterolemic subjects with coronary heart disease. All
      aspects of the RCT except randomization were replicated to the extent possible in
      the GPRD study, which included 2,871 Unexposed and 1,280 statin-treated Exposed
      subjects. RESULTS: Overall mortality [adjusted hazard ratio 0.71 (0.53-0.96)] and
      myocardial infarction [adjusted HR 0.79 (0.61-1.02)] decreased in the GPRD study
      similar to the RCT. Coronary revascularization increased two-fold in the GPRD
      study, whereas it decreased significantly in the RCT [0.63 (0.54-0.74)]. This
      latter disparity prompted use of a new methodology to adjust for unmeasured
      confounding, which yielded an adjusted HR [1.0 (0.75-1.33)] more comparable to
      the RCT. CONCLUSIONS: This study provides additional evidence that a replicated
      GPRD observational study can yield results reasonably similar to a RCT. More
      important, it provides preliminary evidence suggesting that a new analytic
      methodology may adjust for unmeasured confounding, the major limitation to
      research using observational data.

PMID- 18327858
TI  - Nanoemulsions induced by compressed gases.

PMID- 18327859
TI  - Shape and crystal-plane effects of nanoscale ceria on the activity of Au-CeO2
      catalysts for the water-gas shift reaction.

PMID- 18327860
TI  - Cryptand 111: a chemical device for variable-pH kinetic experiments.

PMID- 18327861
TI  - Triplex formation by pyrene-labelled probes for nucleic acid detection in
      fluorescence assays.
AB  - Triplex-forming homopyrimidine oligonucleotides containing insertions of a 2'-5'
      uridine linkage featuring a pyrene moiety at the 3'-position exhibit strong
      fluorescence enhancement upon binding to double-stranded DNA through Hoogsteen
      base pairing. It is shown that perfect matching of the new modification to the
      base pair in the duplex is a prerequisite for strong fluorescence, thus offering
      the potential to detect single mutations in purine stretches of duplex DNA. The
      increase in the fluorescence signal was dependent on the thermal stability of the
      parallel triplex, so a reduction in the pH from 6.0 to 5.0 resulted in an
      increase in thermal stability from 25.0 to 55.0 degrees C and in an increase in
      the fluorescence quantum yield (Phi(F)) from 0.061 to 0.179, while the probe
      alone was fluorescently silent (Phi(F)=0.001-0.004). To achieve higher triplex
      stability, five nucleobases in a 14-mer sequence were substituted with alpha-L
      LNA monomers, which provided a triplex with a T(m) of 49.5 degrees C and a Phi(F)
      of 0.158 at pH 6.0. Under similar conditions, a Watson-Crick-type duplex formed
      with the latter probe showed lower fluorescence intensity (Phi(F)=0.081) than for
      the triplex.

PMID- 18327862
TI  - Identification, synthesis, and enzymology of non-natural glucosinolate
      chemopreventive candidates.
AB  - Isothiocyanates (ITCs) are one of the many classes of breakdown products of
      glucosinolates found in crucifers such as broccoli and are thought to be
      partially responsible for the reduced risk of degenerative diseases associated
      with the consumption of vegetables. The production of ITCs such as L-sulforaphane
      is dependent on the hydrolytic bioactivities of myrosinase, localized both within
      vegetable tissues and within flora of the human GI tract, and is associated with
      important cancer chemopreventive activities. We hypothesized that novel
      isothiocyanates with enhanced chemopreventive properties relative to L
      sulforaphane could be identified and that their glucosinolate precursors could be
      synthesized. From a library of 30 synthetic ITCs, we identified several with
      bioactivities equal or superior to those of L-sulforaphane. The corresponding non
      natural glucosinolate precursors to these novel ITCs were constructed and found
      to be substrates for myrosinase. By utilizing a novel RP-HPLC assay to monitor
      myrosinase-dependent hydrolysis reactions, 2,2-diphenylethyl glucosinolate and
      (biphenyl-2-yl)methyl glucosinolate were shown to exhibit 26.5 and 2.8 %,
      respectively, of the relative activity of sinigrin and produced their
      corresponding ITCs in varying yields. These data support the notion that non
      natural glucosinolates can act as prodrugs for novel ITCs, with a mechanism of
      action reliant on their hydrolytic cleavage by myrosinase. Such non-natural
      glucosinolates may serve as very economical chemopreventive agents for
      individuals at risk for cancers of and around the GI tract.

PMID- 18327863
TI  - Communication in a protein stack: electron transfer between cytochrome c and
      bilirubin oxidase within a polyelectrolyte multilayer.

PMID- 18327864
TI  - Asymmetric iminium ion catalysis: an efficient enantioselective synthesis of
      pyranonaphthoquinones and beta-lapachones.

PMID- 18327865
TI  - Synthesis of ketones from alpha-oxocarboxylates and aryl bromides by Cu/Pd
      catalyzed decarboxylative cross-coupling.

PMID- 18327866
TI  - Sublime arguments: rethinking the generation of homochirality under prebiotic
      conditions.

PMID- 18327867
TI  - Surveillance of suspected adverse reactions to natural health products in Italy.
AB  - PURPOSE: Natural health products are promoted to the public as equally or more
      effective and less toxic than conventional drugs. However, some 'natural'
      medicines, and in particular some herbal medicines, are known to have adverse
      effects. The Italian Pharmacovigilance System, in charge of the Italian Medicines
      Agency, collects spontaneous reports only for registered drugs. The awareness of
      the need of surveillance of the safety of natural health products has stimulated
      the implementation of a suspected adverse reaction reporting system in Italy. The
      system has been set up by the Italian National Institute of Health. METHODS: An
      ad hoc reporting form can be downloaded from different institutional web sites.
      Voluntary reports of suspected adverse reactions are sent to the National
      Institute of Health and are evaluated by a multidisciplinary group of experts.
      RESULTS: From April 2002 to March 2007, 233 spontaneous reports of suspected
      adverse reactions to natural health products were collected. A large proportion
      of suspected adverse reactions were serious: hospitalization was reported in 35%
      of forms; 6% reported life threatening clinical events and two fatal events were
      notified. About 50% of suspected adverse reactions were related to
      gastrointestinal, skin, psychiatric and nervous system disorders. Mainly herbal
      products (66%) were involved. Twenty-one cases of hepatitis of various
      seriousness were reported. Twenty-one reports were associated with 27 homeopathic
      preparations, mostly preparations containing mixtures of substances. Fourteen
      reports regarded suspected reactions to products containing propolis. CONCLUSION:
      Safety and efficacy of 'natural' medicines have not been thoroughly investigated.
      It is important to improve communication with the public on safety issues.
      Encouraging spontaneous reporting can contribute to improve awareness among
      health personnel and patients about the benefit-harm profile of these remedies.

PMID- 18327868
TI  - Spironolactone and gastrointestinal bleeding: a population based study.
AB  - BACKGROUND: Several medical reports showed an increased risk of stomach and
      duodenum bleeding associated with the use of spironolactone. The objective of
      this work is to examine the association between upper gastrointestinal (UGI)
      bleeding and exposure to spironolactone, using a population-based cohort design.
      METHODS: Using the pharmaceutical prescriptions from 2000 to 2006, a cohort was
      identified of residents in Milan (Italy) with chronic exposure to spironolactone
      or other diuretic drugs. The main outcome was defined as the hospital admission
      for UGI bleeding or ulcers. To control for potential bias related to
      spironolactone use, the propensity score was estimated. Then, each patient
      treated with spironolactone was randomly matched with one treated with other
      diuretics and having the same propensity score using the caliper matching method.
      Proportional hazard models were fitted by computing hazard ratios (HR) and the
      corresponding 95% confidence intervals (95%CI). RESULTS: A total of 53 550
      unexposed and 10 564 exposed to spironolactone were identified. Overall in the
      study period, 174 patients (3.2%) developed UGI bleeding in the unexposed and 51
      (4.8%) in the exposed group. HR for UGI bleeding for the spironolactone exposed
      group was 1.94 (95%CI 1.42-2.65). The sensitivity analysis based on the matched
      design using the propensity score showed a statistically significant twofold
      increase of gastrointestinal bleeding only among subjects exposed to high
      spironolactone dose (HR 2.50; 95%CI 1.08-5.79). CONCLUSIONS: Results from a large
      population based study confirm that spironolactone increases the risk of UGI
      bleeding.

PMID- 18327869
TI  - Association between medication and risk of suicide, attempted suicide and death
      in nationwide cohort of suicidal patients with schizophrenia.
AB  - PURPOSE: Mortality among schizophrenia patients is substantially higher than in
      the general population. The aim of this study was to investigate, in a nationwide
      cohort of suicidal schizophrenic individuals, how the risks of suicide, severe
      suicide attempts and death are associated with usage of antidepressant or
      antipsychotic treatment. METHODS: The study population included all individuals
      in Finland who were hospitalised with a diagnosis of attempted suicide between 1
      January 1997 and 31 December 2003, who also had at least one hospitalisation due
      to schizophrenia diagnosis (ICD-10 F20), and were at least 16 years old when the
      index hospitalisation began. Cox's proportional hazards modelling and Bayesian
      intensity estimation were used in the analysis. RESULTS: There were 1611 patients
      with a mean follow-up time of 4.3 years. Current use of antipsychotics was
      associated with decreased mortality due to suicide (HR 0.52, 95% CI 0.34-0.81, p
      = 0.004), but no significant decrease in mortality was observed during current
      use of antidepressants (0.66, 0.41-1.08, p = 0.099), when compared to past use.
      In more detailed analysis when current users were compared to non-users,
      olanzapine, and mixed use of antipsychotics, were associated with reduced all
      cause mortality, and mixed use also with reduced risk of suicide mortality.
      Current use of citalopram was associated with decreased all-cause and suicide
      mortality. CONCLUSIONS: In a population of suicidal schizophrenic individuals
      antipsychotic medication, treatment was associated with lower mortality from
      suicide and all-causes. Antidepressive medication was associated with lower all
      cause mortality when used in combination with antipsychotics.

PMID- 18327870
TI  - Risk factors associated with preterm birth according to gestational age at birth.
AB  - PURPOSE: To identify and quantify risk factors associated with preterm birth,
      stratified by gestational age at birth. METHODS: Three case-control analyses were
      done. Controls were pregnancies of > or =37 weeks of gestational age at birth.
      Cases were defined as: <28, 28-32, 33- <37 weeks of gestational age at birth
      respectively in the three case-control analyses. Women were categorized according
      to whether they carried single or multiple infants. RESULTS: Obstetrical
      conditions (placenta previa, placental abruption), and maternal hypertension were
      significantly associated with preterm delivery in all case-control analyses
      (adjusted OR between 1.34-19.56, p < 0.05). Leading risk factors for preterm
      delivery in singleton pregnancies were placental abruption and placenta previa
      (adjusted ORs 4.85 and 4.13, p < 0.05). For multiple pregnancies they were
      polyhydramnios and maternal hypertension (adjusted ORs 4.39 and 2.45, p < 0.05).
      CONCLUSIONS: Obstetrical conditions during the pregnancy and maternal
      hypertension are important risk factors for preterm birth.

PMID- 18327871
TI  - Depressive symptoms, vascular risk factors, and Alzheimer's disease.
AB  - BACKGROUND: Depressive symptoms in the elderly are associated with an increased
      Alzheimer's disease (AD) risk. We sought to determine whether the association
      between depressive symptoms and AD is explained by a history of vascular risk
      factors and stroke. METHODS: Five hundred and twenty-six elderly persons from New
      York City without dementia at baseline were followed for a mean of 5 years.
      Depressive symptoms were assessed using the 17-item Hamilton Depression Rating
      Scale (HAM). Incident AD was ascertained using standard criteria. Diabetes,
      hypertension, heart disease, current smoking and stroke were ascertained by self
      report. Proportional hazards regression was used to relate HAM scores to incident
      AD. RESULTS: HAM scores were higher in persons with hypertension, heart disease,
      and stroke, which in turn were related to higher AD risk. AD risk increased with
      increasing HAM scores as a continuous logarithmically transformed variable (HR
      for one point increase=1.4; 95% CI=1.1,1.8) and as a categorical variable (HR for
      HAM >or= 10=3.4; 95% CI=1.5,8.1; p for trend=0.004 with HAM=0 as the reference).
      These results were virtually unchanged after adjustment for vascular risk factors
      and stroke, individually (HR for HAM >or= 10=3.4; 95% CI=1.5,8.1; p for trend =
      0.004), and in a composite measure (HR for HAM >or= 10=3.0; 95% CI=1.2,7.8; p for
      trend=0.02). CONCLUSION: The prospective relation between depressive symptoms and
      AD is not explained by a history of vascular risk factors and stroke, suggesting
      that other mechanisms may account for this association.

PMID- 18327872
TI  - Direct and indirect antioxidant properties of inducers of cytoprotective
      proteins.
AB  - Cellular protection against oxidative and electrophile toxicities is provided by
      two types of small-molecule antioxidants: (i) direct antioxidants, which are
      redox active, short-lived, are sacrificed in the process of their antioxidant
      actions and need to be replenished or regenerated, and may evoke pro-oxidant
      effects; and (ii) indirect antioxidants, that may or may not be redox active.
      Indirect antioxidants activate the Keap1/Nrf2/ARE pathway resulting in
      transcriptional induction of a battery of cytoprotective proteins (also known as
      phase 2 enzymes) that act catalytically, are not consumed, have long half-lives,
      and are unlikely to evoke pro-oxidant effects. These protective systems are
      involved in a complex functional interplay, such that many cytoprotective
      proteins participate in the synthesis and/or regeneration of direct antioxidants,
      whereas some direct antioxidants are required for the catalytic functions of
      cytoprotective proteins. Importantly, many inducers of cytoprotective proteins
      have been isolated from edible plants, e. g., sulforaphane from broccoli and
      curcumin from turmeric. Both are pleiotropic agents with multiple biological
      activities that could collectively contribute to their protective effects in
      various animal studies, including models of carcinogenesis, hypertension,
      neuronal and retinal damage. In addition to inducing cytoprotective proteins,
      molecules like curcumin which contain Michael acceptor functionalities (olefins
      or acetylenes conjugated to electron withdrawing groups) and phenolic hydroxyl
      groups can scavenge directly and potently oxygen- and nitrogen-centered reactive
      intermediates. Such bifunctional antioxidants can play a dual protective role by:
      (i) scavenging hazardous oxidants directly and instantaneously, and (ii) inducing
      cytoprotective enzymes that in turn function to resolve the consequences of
      hazardous processes that are already in progress, and to ensure long-term
      protection against subsequent challenges.

PMID- 18327874
TI  - Translating knowledge generated by epidemiological and in vitro studies into
      dietary cancer prevention.
AB  - Epidemiological studies have identified an inverse relationship between ingestion
      of plant foods and cancer risk. However, only approximately 2/3 of such studies
      show this association. Clinical trials based on epidemiological findings require
      preclinical studies to provide insight into reproducibility. The beta carotene
      story is an example of clinical trials based on epidemiological data, before
      mechanism, dose or the bioactive component had been clearly identified. Results
      showed rather than prevention, an increase in lung cancer in smokers.
      Epidemiological studies are used successfully to generate hypotheses for in vitro
      mechanistic studies of isolated components from plant foods, such as sulforaphane
      from broccoli. Yet even these studies are insufficient to plan clinical trials of
      whole foods, since bioavailability, disposition, dose, and effects of the food
      matrix remain unknown. Evidence-based information, from animal and small clinical
      studies carried out prior to clinical trials can assure an optimal design.
      Research into effects of broccoli and sulforaphane make an excellent example of
      how data gaps have closed between epidemiology and clinical trials. Data on
      efficacy of broccoli in animal cancer prevention studies are strong, and small
      clinical studies are emerging. The time is right for clinical trials of purified
      and semipurified sulforaphane, as well as whole broccoli.

PMID- 18327873
TI  - Nutritional calcium modulates colonic expression of vitamin D receptor and
      pregnane X receptor target genes.
AB  - Low nutritional calcium contributes to disruption of the intestinal epithelial
      barrier function, to hyperproliferation of colonocytes and increased occurrence
      of aggressive secondary bile acids in the gut lumen. These mechanisms are also
      known to be involved in the etiology of colonic inflammation and cancer. We
      studied in mice and human adenocarcinoma-derived Caco-2 cells the impact of low
      calcium on markers of inflammation (cyclooxygenase-2; COX-2), of detoxification
      (pregnane and xenobiotic receptor (PXR)/steroid and xenobiotic receptor (SXR),
      cytochrome P450 steroid-inducible 3a11 (CYP3A11)), and on expression of the
      vitamin D system as a protection against tumorigenesis. Caco-2 cells express high
      COX-2 and low SXR mRNA levels when subconfluent. During differentiation this is
      reversed, while low calcium enhanced COX-2 protein expression. In vivo low
      dietary calcium significantly increased the expression of the PXR target gene
      CYP3A11 in the proximal colon, suggesting compensatory defense mechanisms. In
      comparison with males, low nutritional calcium elicits a better protective
      response in females: both the vitamin D synthesizing 25-hydroxyvitamin D(3
      )1alpha hydroxylase (CYP27B1) mRNA and the detoxifying CYP3A11 mRNA are augmented
      more. While it is recognized that colonic vitamin D synthesis may prevent tumor
      progression, low dietary calcium also elevates the 1,25-(OH)(2)-D(3) catabolic 25
      hydroxyvitamin D(3) 24 hydroxylase (CYP24) expression primarily in the proximal
      colon. Our data suggest the proximal colon as the primary site of response to
      insufficient calcium intake.

PMID- 18327875
TI  - Modulation of steroid activity in chronic inflammation: a novel anti-inflammatory
      role for curcumin.
AB  - The expression of NF-kappaB (NF-kappaB)-dependent pro-inflammatory genes in
      response to oxidative stress is regulated by the acetylation-deacetylation status
      of histones bound to the DNA. It has been suggested that in severe asthma and in
      chronic obstructive pulmonary disease (COPD) patients, oxidative stress not only
      activates the NF-kappaB pathway but also alters the histone acetylation and
      deacetylation balance via post-translational modification of histone deacetylases
      (HDACs). Corticosteroids have been one of the major modes of therapy against
      various chronic respiratory diseases such as asthma and COPD. Failure of
      corticosteroids to ameliorate such disease conditions has been attributed to
      their inability to either recruit HDAC2 or to the presence of an oxidatively
      modified HDAC2 in asthmatics and COPD subjects. Naturally occurring polyphenols
      such as curcumin and resveratrol have been increasingly considered as safer
      nutraceuticals. Curcumin is a polyphenol present in the spice turmeric, which can
      directly scavenge free radicals such as superoxide anion and nitric oxide and
      modulate important signaling pathways mediated via NF-kappaB and mitogen
      activated protein kinase pathways. Polyphenols also down-regulate expression of
      pro-inflammatory mediators, matrix metalloproteinases, adhesion molecules, and
      growth factor receptor genes and they up-regulate HDAC2 in the lung. Thus,
      curcumin may be a potential antioxidant and anti-inflammatory therapeutic agent
      against chronic inflammatory lung diseases.

PMID- 18327876
TI  - Short-phase training on a virtual reality simulator improves technical
      performance in tele-robotic surgery.
AB  - BACKGROUND: The da Vinci tele-robot necessitates the acquisition of new skills
      and surgical educators must develop standardized training programmes. It is
      possible that virtual reality (VR) computer simulation maybe used and it is
      necessary to define whether a simulator is an appropriate tool. METHODS: Ten
      surgical novices performed a series of five tasks, ten times on a commercially
      available VR robotic simulator. Two experts repeated the series of tasks twice in
      an attempt to validate the simulator. RESULTS: Each of the five tasks displayed
      statistically significant learning curves. Error scores did not improve
      significantly over successive repetitions except in one task. The experts
      completed two of the tasks in a significantly faster time. CONCLUSIONS: Practice
      sessions on a VR simulator improve technical performance. The simulator enables
      surgeons to mount the early part of the learning curve within a laboratory
      environment, which may lead to a more effective training programme.

PMID- 18327877
TI  - Highly enantioselective friedel-crafts reaction of 4,7-dihydroindoles with imines
      by chiral phosphoric acids: facile access to 2-indolyl methanamine derivatives.

PMID- 18327878
TI  - Rational design of mesoporous metals and related nanomaterials by a soft-template
      approach.
AB  - We review recent developments in the preparation of mesoporous metals and related
      metal-based nanomaterials. Among the many types of mesoporous materials,
      mesoporous metals hold promise for a wide range of potential applications, such
      as in electronic devices, magnetic recording media, and metal catalysts, owing to
      their metallic frameworks. Mesoporous metals with highly ordered networks and
      narrow pore-size distributions have traditionally been produced by using
      mesoporous silica as a hard template. This method involves the formation of an
      original template followed by deposition of metals within the mesopores and
      subsequent removal of the template. Another synthetic method is the direct
      template approach from lyotropic liquid crystals (LLCs) made of nonionic
      surfactants at high concentrations. Direct-template synthesis creates a novel
      avenue for the production of mesoporous metals as well as related metal-based
      nanomaterials. Many mesoporous metals have been prepared by the chemical or
      electrochemical reduction of metal salts dissolved in aqueous LLC domains. As a
      soft template, LLCs are more versatile and therefore more advantageous than hard
      templates. It is possible to produce various nanostructures (e.g., lamellar, 2D
      hexagonal (p6mm), and 3D cubic (Ia?3d)), nanoparticles, and nanotubes simply by
      controlling the composition of the reaction bath.

PMID- 18327880
TI  - Efficient synthesis of symmetrically and unsymmetrically substituted
      hexaphenylbenzene analogues by suzuki-miyaura coupling reactions.
AB  - A series of symmetrically and unsymmetrically substituted hexaphenylbenzene (HPB)
      analogues were efficiently synthesized by using a sterically hindered Suzuki
      Miyaura cross-coupling reaction of arylboronic acids with 1,4-diiodo-2,3,5,6
      tetraarylbenzenes under our optimized reaction conditions. The 1,4-diiodo-2,3,5,6
      tetraarylbenzenes can be readily prepared by using a one-pot Hart reaction.
      Oxidative cyclodehydrogenation of the dibromo derivative with FeCl(3) gave the
      corresponding hexabenzocoronene (HBC) derivative in good yield.

PMID- 18327882
TI  - Synthesis of novel structurally simplified estrogen analogues.
AB  - A library of 17 novel estrogen analogues 3 and 4 containing different
      substituents at rings A and D (steroid nomenclature) was prepared in a five- to
      seven-step synthesis. The key transformation is a Sonogashira-coupling of cyclic
      vinyl iodides of type 7 or 8 with phenylacetylenes of type 9. Reduction of the
      keto function in 3 led to the estradiol analogue 5.

PMID- 18327884
TI  - Highly efficient enrichment of phosphopeptides by magnetic nanoparticles coated
      with zirconium phosphonate for phosphoproteome analysis.
AB  - The location of phosphorylation plays a vital role for the elucidation of
      biological processes. The challenge of low stoichiometry of phosphoproteins and
      signal suppression of phosphopeptides by nonphosphopeptides in mass spectrometry
      (MS) analysis makes the selective enrichment of phosphopeptides prior to MS
      analysis necessary. Besides the immobilized metal affinity chromatography (IMAC)
      method, some affinity methods based on nanoparticles displayed a higher
      enrichment efficiency for phosphopeptides such as Fe(3)O(4)/TiO2 and
      Fe(3)O(4)/ZrO(2) nanoparticles. To further improve the selectivity and
      compatibility of the affinity methods, a novel strategy based on magnetic
      nanoparticles coated with zirconium phosphonate for the enrichment of
      phosphopeptides has been developed in this study. Under optimized experimental
      conditions, 1 x 10(-9) M phosphopeptides in 50 microL tryptic digest of beta
      casein could be enriched and identified successfully. Reliable results were also
      obtained for 1 x 10(-8) M phosphopeptides in 50 microL tryptic digest of beta
      casein in the presence of nonphosphopeptides from a tryptic digest of bovine
      serum albumin (BSA) over 20 times in concentration. The performance of
      nanoparticles for use in a real sample was further demonstrated by employing the
      strong cation-exchange chromatography (SCX) fraction of a tryptic digest of a
      protein extract from Chang liver cells as a model sample. Experimental results
      show that the nanoparticles can be easily and effectively used for enrichment of
      phosphopeptides in low concentration. Most importantly, our approach is more
      compatible with commonly used SCX strategies than Fe(3+)-IMAC. The proposed
      method thus has great potential for future studies of large-scale
      phosphoproteomes.

PMID- 18327885
TI  - Differentiation between isomeric triantennary N-linked glycans by negative ion
      tandem mass spectrometry and confirmation of glycans containing galactose
      attached to the bisecting (beta1-4-GlcNAc) residue in N-glycans from IgG.
AB  - Negative ion tandem mass spectrometry (MS/MS) spectra of three isomeric
      triantennary N-linked glycans provided clear differentiation between the isomers
      and confirmed the occurrence of an isomer that was substituted with galactose on
      a bisecting GlcNAc (1 --> 4-substituted on the core mannose) residue recently
      reported by Takegawa et al. from N-glycans released from human immunoglobulin G
      (IgG). We extend this analysis of human serum IgG to reveal an analogue of the
      fucosylated triantennary glycan reported by Takegawa et al. together with a third
      compound that lacked both the sialic acid and the fucose residues. In addition,
      we demonstrate the biosynthesis of bisected hybrid-type glycans with the
      galactose modification, with and without core fucose, on the stem cell marker
      glycoprotein, 19A, expressed in a partially ricin-resistant human embryonic
      kidney cell line. It would appear, therefore, that this modification of N-linked
      glycans containing a galactosylated bisecting GlcNAc residue may be more common
      than originally thought. Negative ion MS/MS analysis of glycans is likely to
      prove an invaluable tool in the analysis and monitoring of therapeutic
      glycoproteins.

PMID- 18327886
TI  - Direct selection of Pichia pastoris expression strains using new G418 resistance
      vectors.
AB  - The methylotrophic yeast, Pichia pastoris, is widely used as a host organism for
      the expression of heterologous proteins. Currently, the Zeocin and blasticidin
      resistance genes are the only dominant selectable markers that can be used for
      primary selection of transformants. In this report we describe new expression
      vectors that can be used to select directly for P. pastoris transformants using
      G418 resistance conferred by a modified Tn903kan(r) gene. Compared to other
      dominant markers, this system is more economical and offers a higher
      transformation efficiency, due to the small sizes of the cloning vectors, pKAN B
      and pKANalpha B (GenBank Accession Nos EU285585 and EU285586, respectively).
      Additionally, multicopy transformants can be generated using these new vectors.

PMID- 18327887
TI  - The Saccharomyces cerevisiae CLB5 promoter contains two middle sporulation
      elements (MSEs) that are differentially regulated during sporulation.
AB  - The B-type cyclins Clb5 and Clb6 are essential activators of DNA replication
      during sporulation in Saccharomyces cerevisiae. The expression of CLB5 is
      maximally induced during the middle phase of sporulation by the transcription
      factor Ndt80. We have performed an analysis of the CLB5 promoter and have
      identified two middle sporulation elements (MSEs) that act as binding sites for
      Ndt80. Although both MSE sequences bind Ndt80 in vitro, they display differential
      effectiveness in their ability to function as cis-acting regulatory sequences in
      vivo. Mutation of both MSE sequences in the CLB5 promoter profoundly reduces the
      induction of CLB5 transcription during the middle phase of sporulation but
      results in no obvious defect in progression through meiosis and sporulation,
      implying that the Ndt80-dependent induction of CLB5 is not required for effective
      DNA replication or chromosome division.

PMID- 18327888
TI  - Development of a transformation and selection system for the glycolipid-producing
      yeast Candida bombicola.
AB  - Sophorolipids are surface-active compounds synthesized by the non-pathogenic
      yeast Candida bombicola. Over recent decades much effort has been spent to
      optimize culture conditions in order to improve the yield and production process.
      As far as we know, however, hardly any attention has been given to the genetics
      of the producing yeast strain itself and there are no published results available
      on the genetic engineering of C. bombicola. Nevertheless, this can be a useful
      tool for the study of the sophorolipid synthesis pathway and open up perspectives
      for improved production. A first step is the development of a suitable
      transformation and selection method. This article describes the creation and
      selection of an uracil auxotrophic C. bombicola mutant, which can be transformed
      back to prototrophy with the species' own orotidine 5'-phosphate decarboxylase or
      URA3 gene. Successful transformation was confirmed by a PCR-based method
      discriminating between the wild-type and mutated URA3 gene.

PMID- 18327889
TI  - Effectiveness and tolerability of mirtazapine and amitriptyline in alcoholic
      patients with co-morbid depressive disorder: a randomized, double-blind study.
AB  - OBJECTIVE: Studies indicate that serotoninergic and noradrenergic
      pathophysiological mechanisms may underlie both alcohol abuse/dependence and
      depressive disorder. The purpose of this study was to evaluate and compare the
      effectiveness and tolerability of two serotonergic and noradrenergic
      antidepressant drugs-mirtazapine and amitriptyline, for the treatment of patients
      with alcohol dependence co-morbid with depressive disorder in a randomized,
      double-blind treatment setting. METHODS: Forty-four patients were included in the
      study. Twenty-four patients were randomized to mirtazapine and twenty to
      amitriptyline groups. Thirty-six of them completed the study. The 17-item
      Hamilton Depression Rating Scale (HDRS), the Spielberger State-Trait Anxiety
      Inventory (STAI) and alcohol craving questionnaire were used at baseline and, at
      days 7, 14, 28, 42, and 56 to estimate the effectiveness of the antidepressant
      treatment. Michigan Alcoholism Screening Test (MAST) was used in the assessment
      of alcohol dependence. The tolerability was assessed with the Udvalg for Kliniske
      Undersogelser Side Effect Rating Scale (UKU). RESULTS: There was significant
      improvement in HDRS and alcohol craving scores with both the drugs. However there
      were no statistical differences between treatment groups. Mirtazapine was
      tolerated better than amitriptyline treatment. CONCLUSIONS: The treatment with
      either mirtazapine or amitriptyline resulted with the reduction of HDRS and
      craving scores. The side-effect profile of mirtazapine was relatively favorable
      in our study.

PMID- 18327890
TI  - Predicting the NMR spectra of nucleotides by DFT calculations: cyclic uridine
      monophosphate.
AB  - We present an experimental and quantum chemical NMR study of the mononucleotide
      cyclic uridine monophosphate in water. Spectral parameters ((1)H and (13)C
      chemical shifts and (1)H--(1)H, (13)C--(1)H, (31)P--(13)C and (31)P--(1)H spin
      spin coupling constants) have been carefully obtained experimentally and
      calculated using DFT methods including the solvent effect and the conformational
      flexibility of the solute. This study confirms that the (1)H and (13)C spectra of
      polar, flexible molecules in aqueous solution can be predicted with a high level
      of accuracy, comparable to that obtained for less complex systems.

PMID- 18327891
TI  - Anisotropic and hydrogen bonding effects in phenylglyoxamides and mandelamides:
      theoretical and NMR conformational evaluation.
AB  - Interesting anisotropic effects were observed for phenylglyoxamides and their
      respective mandelamides. Such effects were observed in experimental (1)H and
      (13)C NMR (in CDCl(3), CD(3)OD, and DMSO-d(6) solvents) and in some cases with
      good correlation to theoretical (1)H and (13)C NMR DFT-GIAO (B3LYP/6
      311++G**//B3LYP/6-31G*) calculations. A systematic conformational analysis of
      these compounds was performed in a two-step methodology, using PM3 and DFT
      (B3LYP/6-31G*) calculations; with good accomplishment and computational time
      economy. It was observed that intramolecular hydrogen bonding plays a significant
      role in the conformation of such compounds. Finally, a geminal nonequivalence of
      an N-CH(2) moiety, in one of the alkyl side chain (R1 = R2), was found for the
      tertiary mandelamides studied.

PMID- 18327892
TI  - Specificity of immobilized porcine pepsin in H/D exchange compatible conditions.
AB  - Statistical analysis of data from 39 proteins (13 766 amino acid residues)
      digested with immobilized porcine pepsin under conditions compatible with
      hydrogen/deuterium (H/D) exchange (<1 degrees C, <30 s) was performed to examine
      pepsin cleavage specificity. The cleavage of pepsin was most influenced by the
      amino acid residue at position P1. Phe and Leu are favored residues each with a
      cleavage probability greater than 40%. His, Lys, Arg, or Pro residues prohibit
      cleavage when found at the P1 position. Pro also cannot be at position P2
      (cleavage probability <0.3%). Occupation of the P3 position by His, Lys, or Arg,
      or occupation of the P2' position by Pro, also leads to very little cleavage
      (cleavage probability <1.7%). The average cleavage probability over the entire
      data set was 13.6%, which is slightly lower than the value previously obtained by
      Powers et al. (14.8%). This is due, in part, to the larger protein sizes used in
      the current study. While the specificity of pepsin was similar to that previously
      observed, higher selectivity was observed in the present study due to less
      experimental variation in the conditions used to generate our database.

PMID- 18327893
TI  - Dual shell-like magnetic clusters containing Ni(II) and Ln(III) (Ln = La, Pr, and
      Nd) ions.
AB  - Dual shell-like nanoscopic magnetic clusters featuring a polynuclear nickel(II)
      framework encapsulating that of lanthanide ions (Ln = La, Pr, and Nd) were
      synthesized using Ni(NO3)(2).6H2O, Ln(NO3)(3).6H2O, and iminodiacetic acid (IDA)
      under hydrothermal conditions. Structurally established by crystallographic
      studies, these clusters are
      [La20Ni30(IDA)30(CO3)6(NO3)6(OH)30(H2O)12](CO3)(6).72H2O (1),
      [Ln20Ni21(C4H5NO4)21(OH)24(C2H2O3)6(C2O4)3(NO3)9(H2O)12](NO3)9.nH2O [C2H2O3 is
      the alkoxide form of glycolate; Ln = Pr (2), n = 42; Nd (3), n = 50], and
      {[La4Ni5Na(IDA)5(CO3)(NO3)4(OH)5(H2O)5][CO3].10H2O} infinity (4). Carbonate,
      oxalate, and glycolate are products of hydrothermal decomposition of IDA.
      Compositions of these compounds were confirmed by satisfactory elemental
      analyses. It has been found that the cluster structure is dependent on the
      identity of the lanthanide ion as well as the starting Ln/Ni/IDA ratio. The
      cationic cluster of 1 features a core of the Keplerate type with an outer
      icosidodecahedron of Ni(II) ions encaging a dodecahedral kernel of La(III).
      Clusters 2 and 3, distinctly different from 1, are isostructural, possessing a
      core of an outer shell of 21 Ni(II) ions encapsulating an inner shell of 20
      Ln(III) ions. Complex 4 is a three-dimensional assembly of cluster building
      blocks connected by units of Na(NO3)/La(NO3)3; the structure of the building
      block resembles closely that of 1, with a hydrated La(III) ion internalized in
      the decanuclear cage being an extra feature. Magnetic studies indicated
      ferromagnetic interactions in 1, while overall antiferromagnetic interactions
      were revealed for 2 and 3. The polymeric, three-dimensional cluster network 4
      displayed interesting ferrimagnetic interactions.

PMID- 18327894
TI  - Heterometallic integer-spin analogues of S = 9/2 Mn4 cubane single-molecule
      magnets.
AB  - A family of distorted heterometallic cubanes, [Mn (III) 3Ni (II)(hmp) 3O(N 3) 3(O
      2CR) 3], where O 2CR (-) is benzoate ( 1), 3-phenylpropionate ( 2), 1
      adamantanecarboxylate ( 3), or acetate ( 4) and hmp (-) is the anion of 2
      pyridinemethanol, was synthesized and structurally as well as magnetically
      characterized. These complexes have a distorted-cubane core structure similar to
      that found in the S = 9/2 Mn 4 cubane family of complexes. Complexes 1, 3, and 4
      crystallize in rhombohedral, hexagonal, and cubic space groups, respectively, and
      have C 3 molecular symmetry, while complex 2 crystallizes in the monoclinic space
      group Cc with local C 1 symmetry. Magnetic susceptibility and magnetization
      hysteresis measurements and high-frequency electron paramagnetic resonance
      (HFEPR) spectroscopy established that complexes 1-4 have S = 5 spin ground states
      with axial zero-field splitting (ZFS) parameters ( D) ranging from -0.20 to -0.33
      cm (-1). Magnetization versus direct-current field sweeps below 1.1 K revealed
      hysteresis loops with magnetization relaxation, definitely indicating that
      complexes 1-4 are single-molecule magnets that exhibit quantum tunneling of
      magnetization (QTM) through an anisotropy barrier. Complex 2 exhibits the
      smallest coercive field and fastest magnetization tunneling rate, suggesting a
      significant rhombic ZFS parameter ( E), as expected from the low C 1 symmetry.
      This was confirmed by HFEPR spectroscopy studies on single crystals that gave the
      following parameter values for complex 2: gz = 1.98, gx = gy = 1.95, D = -0.17 cm
      (-1), B 4 (0) = -6.68 x 10 (-5) cm (-1), E = 6.68 x 10 (-3) cm (-1), and B 4 (2)
      = -1.00 x 10 (-4) cm (-1). Single-crystal HFEPR data for complex 1 gave g z =
      2.02, gx = gy = 1.95, D = -0.23 cm (-1), and B 4 (0) = -5.68 x 10 (-5) cm (-1),
      in keeping with the C 3 site symmetry of this Mn 3Ni complex. The combined
      results highlight the importance of spin-parity effects and molecular symmetry,
      which determine the QTM rates.

PMID- 18327895
TI  - A new class of binuclear and trinuclear iron-sulfur clusters derived from
      bis[bis(trimethylsilyl)amido]iron(II).
AB  - The compound Fe[N(SiMe 3) 2] 2 is shown to be a useful precursor to dinuclear and
      trinuclear iron-sulfur-silylamido complexes by reaction with thiols or thiols and
      sulfur in tetrahydrofuran (THF) or toluene. Reaction with 1 equiv of p-tolylthiol
      affords [Fe 2(mu 2-S- p-tol) 2(N(SiMe 3) 2) 2(THF) 2] ( 1); with 0.5 equiv of
      adamantane-1-thiol, [Fe 2(mu 2-S-1-Ad)(mu 2-N(SiMe 3) 2)(N(SiMe 3) 2) 2] ( 2) is
      formed. The clusters [Fe 3(mu 3-Q)(mu 2-SR) 3(N(SiMe 3) 2) 3] are available by
      three methods: (i) self-assembly in the systems Fe[N(SiMe 3) 2] 2/RSH/S or Se [Q
      = S, R = p-tol ( 3) and 1-Ad ( 5)]; (ii) reaction of 1 with Q = S or Se to yield
      3 or [Fe 3Se(S- p-tol) 3(N(SiMe 3) 2) 3] ( 4); (iii) reaction of 2 with 1-AdSH
      and S to give 5. Structures of 1- 5 are presented. Complexes 1 and 2 contain
      planar Fe 2S 2 and Fe 2SN rhombs. Clusters 3- 5 contain a mixed-valence Fe 3Q(SR)
      3 core with trigonal (cuboidal) geometry. Of known iron-sulfur clusters, these
      most closely resemble previously reported [Fe 3S(S-R-S) 3] (2-) stabilized by
      bidentate thiolate ligands. Complexes 1- 5, together with a small set of recently
      described clusters of nuclearities 2, 4, and 8, constitute a new class of iron
      sulfur-silylamido clusters. Complexes 3- 5 constitute a new structure type of
      mixed-valence iron-sulfur clusters.

PMID- 18327896
TI  - Luminescent osmium(II) complexes with functionalized 2-phenylpyridine chelating
      ligands: preparation, structural analyses, and photophysical properties.
AB  - Cyclometalated osmium complexes with the formulas [Os(ppy) 2(CO) 2] ( 1a, b),
      [Os(dfppy) 2(CO) 2] ( 2a, b), and [Os(btfppy) 2(CO) 2] ( 3a, b) have been
      synthesized, for which the chelating chromophores ppyH, dfppyH, and btfppyH
      denote 2-phenylpyridine, 2-(2,4-difluorophenyl)pyridine, and 2-(2,4
      bis(trifluoromethyl)phenyl)pyridine, respectively. The isomers 1a- 3a, possessing
      an intrinsic C 2 rotational axis as determined by single-crystal X-ray
      diffraction analysis, underwent slow isomerization in solution at elevated
      temperature, giving the respective thermodynamic products 1b- 3b, which showed a
      distinctive coordination arrangement produced by a 180 degrees rotation of one
      cyclometalated ligand around the Os(II) metal center. In contrast to the case for
      1a, b and 2a, which are inert to substitution, complexes 2b and 3b (or 3a)
      readily react with PPh 2Me to afford the products [Os(dfppy) 2(CO)(PPh 2Me)] ( 4)
      and [Os(btfppy) 2)(PPh 2Me)] ( 6), in which the incoming PPh 2Me replaced the CO
      located trans to the carbon atom of one cyclometalated ligand. UV-vis and
      emission spectra were measured, revealing the lowest excited state for all
      complexes as a nominally ligand-centered (3)pipi* state mixed with certain MLCT
      character. Introduction of the electron-withdrawing substituents on the
      cyclometalated chelates or replacement of one CO ligand with phosphine at the
      metal center increased the MLCT contribution in the first excited state, giving a
      broad and featureless emission with greatly enhanced quantum yields.

PMID- 18327897
TI  - Phosphoproteome analysis of Drosophila melanogaster embryos.
AB  - Protein phosphorylation is a key regulatory event in most cellular processes and
      development. Mass spectrometry-based proteomics provides a framework for the
      large-scale identification and characterization of phosphorylation sites. Here,
      we used a well-established phosphopeptide enrichment and identification strategy
      including the combination of strong cation exchange chromatography, immobilized
      metal affinity chromatography, and high-accuracy mass spectrometry
      instrumentation to study phosphorylation in developing Drosophila embryos. In
      total, 13,720 different phosphorylation sites were discovered from 2702 proteins
      with an estimated false-discovery rate (FDR) of 0.63% at the peptide level.
      Because of the large size of the data set, both novel and known phosphorylation
      motifs were extracted using the Motif-X algorithm, including those representative
      of potential ordered phosphorylation events.

PMID- 18327898
TI  - Advances in the analysis of protein phosphorylation.
AB  - Phosphorylation is one of the most relevant and ubiquitous post-translational
      modifications. Despite its relevance, the analysis of protein phosphorylation has
      been revealed as one of the most challenging tasks due to its highly dynamic
      nature and low stoichiometry. However, the development and introduction of new
      analytical methods are modifying rapidly and substantially this field. Especially
      important has been the introduction of more sensitive and specific methods for
      phosphoprotein and phosphopeptide purification as well as the use of more
      sensitive and accurate MS-based analytical methods. The integration of both
      approaches has enabled large-scale phosphoproteome studies to be performed, an
      unimaginable task few years ago. Additionally, methods originally developed for
      differential proteomics have been adapted making the study of the highly dynamic
      nature of protein phosphorylation feasible. This review aims at offering an
      overview on the most frequently used methods in phosphoprotein and phosphopeptide
      enrichment as well as on the most recent MS-based analysis strategies. Current
      strategies for quantitative phosphoproteomics and the study of the dynamics of
      protein phosphorylation are highlighted.

PMID- 18327899
TI  - Structure-activity relationships among the nitrogen containing bisphosphonates in
      clinical use and other analogues: time-dependent inhibition of human farnesyl
      pyrophosphate synthase.
AB  - The nitrogen-containing bisphosphonates (N-BPs) are the main drugs currently used
      to treat diseases characterized by excessive bone resorption. The major molecular
      target of N-BPs is farnesylpyrophosphate synthase. N-BPs inhibit the enzyme by a
      mechanism that involves time dependent isomerization of the enzyme. We
      investigated features of N-BPs that confer maximal slow and tight-binding by
      quantifying the initial and final K(i)s and calculating the isomerization
      constant K(isom) for many N-BPs. Disruption of the phosphonate-carbon-phosphonate
      backbone resulted in loss of potency and reduced K(isom). The lack of a hydroxyl
      group on the geminal carbon also reduced K(isom). The position of the nitrogen in
      the side chain was crucial to both K(i) and K(isom). A correlation of K(isom) and
      also final K(i) with previously published in vivo potency reveals that the
      isomerization constant ( R = -0.77, p < 0.0001) and the final inhibition of FPPS
      by N-BPs ( R = 0.74, p < 0.0001) are closely linked to antiresorptive efficacy.

PMID- 18327900
TI  - A probabilistic approach to classifying metabolic stability.
AB  - Metabolic stability is an important property of drug molecules that should
      optimally-be taken into account early on in the drug design process. Along with
      numerous medium- or high-throughput assays being implemented in early drug
      discovery, a prediction tool for this property could be of high value. However,
      metabolic stability is inherently difficult to predict, and no commercial tools
      are available for this purpose. In this work, we present a machine learning
      approach to predicting metabolic stability that is tailored to compounds from the
      drug development process at Bayer Schering Pharma. For four different in vitro
      assays, we develop Bayesian classification models to predict the probability of a
      compound being metabolically stable. The chosen approach implicitly takes the
      "domain of applicability" into account. The developed models were validated on
      recent project data at Bayer Schering Pharma, showing that the predictions are
      highly accurate and the domain of applicability is estimated correctly.
      Furthermore, we evaluate the modeling method on a set of publicly available data.

PMID- 18327901
TI  - Role of the phosphine ligands on the stabilization of monoadducts of the model
      nucleobases 1-methylcytosine and 9-methylguanine in platinum(II) complexes.
AB  - The addition of 1-methylcytosine (1-MeCy) or 9-methylguanine (9-MeGu) to
      solutions of cis-(PPh3)2P(ONO2)2 (1a), in a molar ratio of 1:1, affords the
      monoadducts cis-[(PPh3)2Pt(1-MeCy)(ONO2)]NO3 (2a) and cis-[(PPh3)2Pt(9
      MeGu)(ONO2)]NO3 (3a) and only trace amounts of the bisadducts cis-[(PPh3)2Pt(1
      MeCy)2](NO3)2 (4a) and cis-[(PPh3)2Pt(9-MeGu)2](NO3)2 (5a), respectively. The X
      ray structural determination of 2a and 3a indicates a strong pi-pi stacking
      interaction between one of the PPh3 phenyl groups and the pyrimydinic N3
      platinated cytosine or the imidazole part of the N7-coordinated guanine base. The
      addition of a further equiv of nucleobase to the monoadducts forms quantitatively
      the bisadducts that have been isolated as pure compounds 4a and 5a. Under the
      same experimental conditions, the dinitrato analogue cis-[(PMePh2)2Pt(ONO2)2]
      (1b) forms the monoadducts 2b and 3b in equilibrium with a relatively high
      concentration (20-30%) of the bisadducts cis-[(PMePh2)2Pt(1-MeCy)2](NO3)2 (4b)
      and cis-[(PMePh2)2Pt(9-MeGu)2](NO3)2 (5b), which have been structurally
      characterized by single-crystal X-ray analysis. The characterization of the
      isolated complexes by multinuclear NMR spectroscopy is also described.

PMID- 18327902
TI  - Metal effects on electronic structures of directly linked tribenzotetraazachlorin
      fullerene conjugates.
AB  - Mixed condensation of 1,2-dicyanofullerene (1) and 4,5-dibutyloxyphthalonitrile
      (2a) in the presence of vanadium(III) chloride (VCl3) in quinoline forms the
      hexabutyloxy-substituted tribenzotetraazachlorin (TBTAC) - fullerene (C60)
      vanadyl complex (3). UV-vis absorption and magnetic circular dichroism (MCD)
      spectroscopy demonstrated that 3 shows two intense Q-band components, whereas the
      previously reported nickel complex possessing the identical peripheral
      substituents (4) shows one intense and two medium-intense bands in the 600-800 nm
      region, indicating that the electronic mixing states of 3 are different from
      those of the nickel complex (4). The metal effects on electronic structures of
      the conjugates were interpreted using density functional theory (DFT)
      calculations.

PMID- 18327903
TI  - Simplified speciation and improved phosphodiesterolytic activity of hydroxo
      complexes of trivalent lanthanides in aqueous DMSO.
AB  - Potentiometric titrations of La(III), Nd(III), and Eu(III) perchlorates by Me
      4N(OH) in 80% vol aq DMSO revealed formation of predominantly mononuclear
      complexes M(OH)n(3- n) (n = 1, 2, or 3) and a single binuclear complex
      M2(OH)(5+). Kinetics of the cleavage of two phosphate diesters, bis (4
      nitrophenyl) phosphate (BNPP) and 2-hydroxypropyl 4-nitrophenyl phosphate
      (HPNPP), and a triester, 4-nitrophenyl diethyl phosphate (paraoxon), were studied
      as a function of metal and Me4N(OH) concentrations in the same medium. Rate of
      BNPP cleavage is second-order in metal and is proportional to the product of
      concentrations of M(OH)2(+) and M(OH)3 species. Rate of HPNPP cleavage is
      proportional to [M(OH)3](3) for La(III) and Nd(III) and to [M(OH)3](2) for
      Eu(III). Proposed mechanism for BNPP hydrolysis involves formation of
      M2(OH)5(diester) intermediate followed by intramolecular nucleophilic attack of
      hydroxide anion on the phosphoryl group of the substrate. Proposed mechanism for
      HPNPP cleavage involves formation of M3(OH)9(diester)(-) or M2(OH)6(diester)(-)
      intermediates followed by the general base-assisted intramolecular cyclization of
      HPNPP. The latter mechanism is supported by observation of the solvent kinetic
      isotope effect k H/kD = 2.9 for Eu(III) catalyzed HPNPP cleavage. The efficiency
      of catalysis in 80% DMSO is much higher than in water. The reaction rate observed
      in the presence of 1 mM metal in neutral solution surpasses the rate of
      background hydrolysis by a factor of 10(12)-10(13) for BNPP and 10(10) for HPNPP.
      The increased catalytic activity is attributed principally to the preferable
      solvation of lanthanide ions by DMSO, which creates an anhydrous microenvironment
      favorable for reaction in the coordination sphere of the catalyst. The catalytic
      activity of lanthanides in paraoxon hydrolysis is much lower with the estimated
      efficiency of catalysis about 10(5) for 1 mM La(III).

PMID- 18327904
TI  - Complexities in the ring-opening polymerization of lactide by chiral salen
      aluminum initiators.
AB  - The preparation of (R, R)- and (S, S)-salen Al(OR) complexes, where R = Et,
      CH2(i)Pr, CH2(t)Bu, and CH2CH(S)MeCl, are reported, along with their reactions
      with rac-lactide (salen = N, N'-bis(3,5-di-tert-butylsalicylidene)-1,2
      cyclohexanediamino). Rapid, reversible coordination of LA to the salen metal
      complex is observed, and it is shown that the relative rates of alcohol/alkoxide
      exchange are comparable to the NMR time scale while the rate of chain transfer
      involving (R, R)-salenAl(O-R-R) and (S, S)-salenAl(O-S-R) is much faster than the
      initial rate of ring opening of the LA monomer. For a primary [Al-OR] moiety, the
      ring opening of rac-LA is much faster than the ring-opening
      polymerization/enchainment of LA, and in the initial ring-opening event, the
      diastereoselectivity is dependent on the solvent, the chirality of the salen
      ligand, and the OR group. Irrespective of the initiator group OR or the solvent,
      the system moves to a pseudostatic equilibrium concentration of L- and D-LA which
      is dependent on the nature of the chirality of the salen ligand. Further studies
      show that the relative rate of trans-esterification is slower than the rate of LA
      enchainment and that the rate of epimerization is the slowest reaction in the
      system. Adventitious water leads to loss of catalytic activity and formation of
      the inert oxo-bridged compound [(salen)Al]2(mu-O) which has been structurally
      characterized.

PMID- 18327905
TI  - Probing the electronic and structural properties of chromium oxide clusters
      (CrO3)n(-) and (CrO3)n (n = 1-5): photoelectron spectroscopy and density
      functional calculations.
AB  - Photoelectron spectroscopy has been conducted for a series of (CrO3)n(-) (n = 1
      5) clusters and compared with density functional calculations. Well-resolved
      photoelectron spectra were obtained for (CrO3)n(-) (n = 1-5) at 193 nm (6.424 eV)
      and 157 nm (7.866 eV) photon energies, allowing for accurate measurements of the
      electron binding energies, low-lying electronic excitations for n = 1 and 2, and
      the energy gaps. Density functional and molecular orbital theory (CCSD(T))
      calculations were performed to locate the ground and low-lying excited states for
      the neutral clusters and to calculate the electron binding energies of the
      anionic species. The experimental and computational studies firmly establish the
      unique low-spin, nonplanar, cyclic ring structures for (CrO3)n and (CrO3)n(-) for
      n > or = 3. The structural parameters of (CrO3)n are shown to converge rapidly to
      those of the bulk CrO3 crystal. The extra electron in (CrO3)n(-) (n > or = 2) is
      shown to be largely delocalized over all Cr centers, in accord with the
      relatively sharp ground-state photoelectron bands. The measured energy gaps of
      (CrO3)n exhibit a sharp increase from n = 1 to n = 3 and approach to the bulk
      value of 2.25 eV at n = 4 and 5, consistent with the convergence of the
      structural parameters.

PMID- 18327906
TI  - In vitro antioxidant properties and phenolic composition of Salvia virgata Jacq.
      from Turkey.
AB  - Antioxidant activities and phenolic compositions of the active fractions of
      Salvia virgata Jacq. (Lamiaceae) from Turkey were examined. The aerial part of S.
      virgata was extracted with different solvents in an order of increasing polarity
      such as hexane, ethyl acetate, methanol, and 50% aqueous methanol using a Soxhlet
      apparatus. Water extract was also prepared from S. virgata by reflux. All solvent
      fractions were investigated for their total phenolic contents, total flavonoids,
      flavonols, qualitative-quantitative compositions (by HPLC-PDA analysis),
      iron(III) reductive activities, free radical scavenging activities (using DPPH*),
      and effect upon linoleic acid peroxidation activities; also, the peroxidation
      level was determined by the TBA method. The results of activity tests given as
      IC50 values were estimated from nonlinear algorithm and compared with standards,
      viz., butylated hydroxytoluene, ascorbic acid, and gallic acid. Polar fractions
      were found to be more active for free radical activity whereas nonpolar fractions
      protected the peroxidation of linoleic acid. Rosmarinic acid was the most
      abundant component in the extracts, followed by caffeic acid and lutelin-7- O
      glycoside.

PMID- 18327907
TI  - Bioaccumulation potential of dietary arsenic, cadmium, lead, mercury, and
      selenium in organs and tissues of rainbow trout (Oncorhyncus mykiss) as a
      function of fish growth.
AB  - The distribution and potential bioaccumulation of dietary arsenic, cadmium, lead,
      mercury, and selenium in organs and tissues of rainbow trout (Oncorhyncus mykiss
      Walbaum, 1792), a major aquaculture species, was studied in relation to fish
      growth over a period of >3 years. Fish were reared under normal farming
      conditions, that is, fed a standard fish food and exposed to negligible levels of
      waterborne trace elements. The age-related variations in the content of each
      trace element in gills, kidney, liver, muscle, and skin were studied through
      nonparametric regression analysis. A buildup of all elements in all tissues and
      organs was observed, but due to dilution with growth, the concentrations did not
      increase, except in a few cases such as cadmium and mercury in liver and kidney.
      In muscle tissue, the concentrations of mercury, lead, and selenium did not alter
      significantly with growth, whereas cadmium increased but remained at exceedingly
      low levels. The concentration of arsenic in muscle tissue peaked at 14 months and
      then decreased in adult specimens. Arsenic speciation by high-performance liquid
      chromatography--inductively coupled plasma mass spectrometry revealed that
      arsenic in muscle was almost exclusively present in the form of nontoxic
      arsenobetaine. Application of a mercury mass balance model gave predicted
      concentrations in agreement with measured ones and showed that in farmed rainbow
      trout the ratio of mercury concentrations in feed and in fish is about 1:1.
      Therefore, rainbow trout does not approach the limits established for human
      consumption even when reared with feed at the maximum permitted levels. These
      findings highlight the low bioaccumulation potential of toxic trace elements such
      as cadmium, lead, and mercury in rainbow trout following dietary exposure. On the
      other hand, selenium concentrations in muscle (about 0.2 microg g (-1) of fresh
      weight) show that rainbow trout may be a good source of this essential element.

PMID- 18327908
TI  - Collagen-based biomimetic nanofibrous scaffolds: preparation and characterization
      of collagen/silk fibroin bicomponent nanofibrous structures.
AB  - Electrospinning of collagen (COL)/silk fibroin (SF) blend solutions in
      1,1,1,3,3,3-hexafluoro-2-propanol was investigated for fabrication of a
      biocompatible and biomimetic nanostructured scaffold for tissue engineering. The
      morphology of the electrospun COL/SF blend nanofibers was observed by scanning
      electron microscopy. The average diameters of COL/SF blend fibers ranged from 320
      to 360 nm, irrespective of SF content in the blends. Both COL and SF components
      in the as-spun COL/SF blend matrices were stabilized by glutaraldehyde and water
      vapor, respectively, under the saturated glutaraldehyde aqueous solution at 25
      degrees C. The glutaraldehyde vapor chemically stabilized the COL component via
      cross-linking, whereas the water vapor physically stabilized the SF component via
      crystallization to the beta-sheet structure. These structural changes of after
      treated COL/SF blend matrices were examined using ATR-IR and CP/MAS (13)C NMR
      spectroscopy. To assay the cytocompatibility and cellular behavior of the COL/SF
      blend nanofibrous scaffolds, cell attachment and the spreading of normal human
      epidermal keratinocytes (NHEK) and fibroblasts (NHEF) seeded on the scaffolds
      were studied. In addition, both morphological changes and cellular responses of
      COL/SF blend nanofibrous matrices were also compared with COL/SF hybrid
      nanofibrous matrices. Generally similar levels of cell attachment and spreading
      of NHEF were shown in the COL/SF blend nanofibrous matrix compared with those of
      the pure COL and pure SF matrices; the cellular responses of NHEK were, however,
      markedly decreased in the COL/SF blend nanofibrous matrix as compared to the pure
      matrices. In contrast, cell attachment and spreading of NHEK on the COL/SF hybrid
      nanofibrous matrix were significantly higher than that of the COL/SF blend
      nanofibrous matrix. Our results indicate that a COL/SF hybrid nanofibrous matrix
      may be a better candidate than a COL/SF blend nanofibrous matrix for biomedical
      applications such as wound dressing and scaffolds for tissue engineering.

PMID- 18327909
TI  - Synthesis of kalasinamide, a putative plant defense phototoxin.
AB  - The first total synthesis of the azaanthracene kalasinamide (1) is described, and
      the discrepancy in the reported (13)C NMR data and melting points for the natural
      product from two different sources is resolved. Kalasinamide is prone to
      autosensitized photooxidation, in solution and in the solid state, to give the
      corresponding quinone, marcanine A (8). This transformation may be representative
      of a novel and more general step in the biosynthesis of (aza)anthraquinones.
      Through its ability to generate toxic singlet oxygen, kalasinamide may serve a
      protective role, defending the plant against predation and the invasion of
      microbial pathogens, following mechanical insult.

PMID- 18327910
TI  - Structure and conformational dynamics of trichothecene mycotoxins.
AB  - A combination of NMR spectroscopy and molecular modeling has been employed to
      characterize the conformation and dynamics of the macrolide ring in verrucarin A
      and roridin A, two closely related toxins in the trichothecene mycotoxin family.
      Longitudinal carbon-13 relaxation times demonstrate the relative flexibility of
      the macrolide ring. The calculations, NOEs, and scalar vicinal coupling constants
      show that verrucarin A in CDCl 3 and CD 2Cl 2 predominantly adopts a single, well
      defined conformation that matches the crystal structure. In contrast, roridin A
      is present as a mixture of two conformers.

PMID- 18327911
TI  - Antineoplastic agents. 536. New sources of naturally occurring cancer cell growth
      inhibitors from marine organisms, terrestrial plants, and microorganisms(1a,).
AB  - Bioassay-guided fractionation of extracts of various plants, marine organisms,
      and microorganisms has led to the discovery of new natural sources of a number of
      known compounds that have significant biological activity. The isolation of
      interesting and valuable cancer cell growth inhibitors including majusculamide C
      ( 1), axinastatin 5 ( 5), bengazoles A ( 6), B ( 7), and E ( 8), manzamine A (
      10), jaspamide ( 11), and neoechinulin A ( 19) has been summarized.

PMID- 18327912
TI  - Glycosides from the root of Iodes cirrhosa.
AB  - Seven new neolignan glycosides ( 1- 7), two arylglycerol glycosides ( 8, 9), and
      18 known glycosides have been isolated from an ethanolic extract of the root of
      Iodes cirrhosa. Their structures including absolute configurations were
      determined by spectroscopic and chemical methods. Based on analysis of the NMR
      data of threo and erythro 8-4'-oxyneolignans and arylglycerols in different
      solvents, the validity of J 7,8 and Deltadelta C8-C7 values to distinguish threo
      and erythro derivatives was discussed. In the in vitro assays, compound 4 and
      liriodendrin ( 17) both showed activity against glutamate-induced PC12 cell
      damage at 10 (-5) M.

PMID- 18327913
TI  - Widely distributed residues in thymosin beta4 are critical for actin binding.
AB  - We have investigated the contributions of hydrophobic residues, the conserved and
      variable proline residues, and the conserved lysine residues to the affinity and
      kinetics of thymosin beta4 (Tbeta4) binding to MgATP-actin monomers. Pro4, Lys18,
      Lys19, Pro27, Leu28, Pro29, and Ile34 were substituted with alanine residues.
      Mutagenesis of Pro4 or Pro27 has little effect (<or=3-fold reduction) on the
      actin binding affinity of Tbeta4. Substitution of Lys18 and Lys19, Leu28, Pro29,
      or Ile34 weakens the affinity of the actin-Tbeta4 complex >or=10-fold, but the
      kinetic basis of the lower stability varies among the mutants. Substitution of
      the conserved lysine residues weakens the affinity by slowing association and
      accelerating dissociation. Substitution of hydrophobic residue Leu28 or Ile34
      weakens the affinity by accelerating dissociation. These results favor a reaction
      mechanism in which Tbeta4 binds actin monomers following a two-step mechanism in
      which the formation of a bimolecular complex is followed by isomerization to a
      strong binding state that is coupled to the formation of widely distributed
      hydrophobic contacts. The isomerization equilibrium is slowed by mutagenesis of
      Pro29, as revealed by the double-exponential time course of association.
      Mutagenesis of Pro4 or Pro27 accelerates binding and dissociation but minimally
      affects the binding affinity (<or=3-fold reduction), suggesting that cis- trans
      isomerization of these proline residues contributes to the slow association rate
      constant of wild-type Tbeta4.

PMID- 18327914
TI  - Platelet endothelial cell adhesion molecule 1 (PECAM-1) and its interactions with
      glycosaminoglycans: 2. Biochemical analyses.
AB  - Platelet endothelial cell adhesion molecule 1 (PECAM-1) (CD31), a member of the
      immunoglobulin (Ig) superfamily of cell adhesion molecules with six Ig-like
      domains, has a range of functions, notably its contributions to leukocyte
      extravasation during inflammation and in maintaining vascular endothelial
      integrity. Although PECAM-1 is known to mediate cell adhesion by homophilic
      binding via domain 1, a number of PECAM-1 heterophilic ligands have been
      proposed. Here, the possibility that heparin and heparan sulfate (HS) are ligands
      for PECAM-1 was reinvestigated. The extracellular domain of PECAM-1 was expressed
      first as a fusion protein with the Fc region of human IgG1 fused to domain 6 and
      second with an N-terminal Flag tag on domain 1 (Flag-PECAM-1). Both proteins
      bound heparin immobilized on a biosensor chip in surface plasmon resonance (SPR)
      binding experiments. Binding was pH-sensitive but is easily measured at slightly
      acidic pH. A series of PECAM-1 domain deletions, prepared in both expression
      systems, were tested for heparin binding. This revealed that the main heparin
      binding site required both domains 2 and 3. Flag-PECAM-1 and a Flag protein
      containing domains 1-3 bound HS on melanoma cell surfaces, but a Flag protein
      containing domains 1-2 did not. Heparin oligosaccharides inhibited Flag-PECAM-1
      from binding immobilized heparin, with certain structures having greater
      inhibitory activity than others. Molecular modeling similarly identified the
      junction of domains 2 and 3 as the heparin-binding site and further revealed the
      importance of the iduronic acid conformation for binding. PECAM-1 does bind
      heparin/HS but by a site that is distinct from that required for homophilic
      binding.

PMID- 18327915
TI  - Inhibition mechanism of the acetylcholine receptor by alpha-neurotoxins as
      revealed by normal-mode dynamics.
AB  - The nicotinic acetylcholine receptor (AChR) is the prototype of ligand-gated ion
      channels. Here, we calculate the dynamics of the muscle AChR using normal modes.
      The calculations reveal a twist-like gating motion responsible for channel
      opening. The ion channel diameter is shown to increase with this twist motion.
      Strikingly, the twist motion and the increase in channel diameter are not
      observed for the AChR in complex with two alpha-bungarotoxin (alphaBTX)
      molecules. The toxins seems to lock together neighboring receptor subunits,
      thereby inhibiting channel opening. Interestingly, one alphaBTX molecule suffices
      to prevent the twist motion. These results shed light on the gating mechanism of
      the AChR and present a complementary inhibition mechanism by snake-venom-derived
      alpha-neurotoxins.

PMID- 18327916
TI  - Three-dimensional structure of DesVI from Streptomyces venezuelae: a sugar N,N
      dimethyltransferase required for dTDP-desosamine biosynthesis.
AB  - D-Desosamine, or 3-(dimethylamino)-3,4,6-trideoxyglucose, is an unusual sugar
      found on the macrolide antibiotic erythromycin, and it has been shown to play a
      critical role in the biological activity of the drug. Desosamine is added to the
      parent aglycone via the action of a glycosyltransferase that utilizes dTDP
      desosamine as its substrate. Six enzymes are required for the biosynthesis of
      dTDP-desosamine in Streptomyces venezuelae, with the last step catalyzed by
      DesVI, an N, N-dimethyltransferase. Here we describe the X-ray crystal structure
      determined to 2.0 A resolution of DesVI complexed with S-adenosylmethionine (SAM)
      and the substrate analogue UDP-benzene. Each subunit of the DesVI dimer contains
      a seven-stranded mixed beta-sheet flanked on either side by alpha-helices. In
      addition to this major tertiary structural element, there is a four-stranded
      antiparallel beta-sheet that provides the platform necessary for subunit-subunit
      assembly. On the basis of the UDP-benzene binding mode, the DesVI substrate, dTDP
      3-(methylamino)-3,4,6-trideoxyglucose, has been modeled into the active site.
      This model places the C-6' methyl group of the sugar into a hydrophobic patch
      that is well-conserved among putative nucleotide-linked sugar
      dimethyltransferases. It is formed by Trp 140, Met 178, and Ile 200. The sugar C
      2' hydroxyl sits near Tyr 14, and its C-3' amino group is properly positioned for
      direct in-line attack of the cofactor's reactive methyl group. While
      methyltransferases that catalyze single alkylations at carbons, oxygens, sulfurs,
      and nitrogens have been well characterized, little is known regarding enzymes
      capable of N,N-dimethylation reactions. As such, the ternary structure of DesVI
      reported here serves as a structural paradigm for a new family of
      dimethyltransferases that function on nucleotide-linked sugars.

PMID- 18327917
TI  - Syntheses of oxazabicycle library via one-pot tandem reactions.
AB  - A practical protocol for the preparation of a parallel solution-phase library of
      oxazabicycle is reported. Target compounds were obtained in moderate to good
      yields by a Yb(OTf)3-catalyzed one-pot tandem reaction from various anisidines,
      aromatic aldehydes, isobutyraldehyde, and 4-hydroxycoumarins/dimedone.
      Purification of the final products by either recrystallization in ethyl
      acetate/methylene chloride or column chromatography allowed easy isolation of the
      18 components of the array.

PMID- 18327918
TI  - Intramolecular energy transfer within butadiyne-linked chlorophyll and porphyrin
      dimer-faced, self-assembled prisms.
AB  - The synthesis and photophysical properties of butadiyne-linked chlorophyll and
      porphyrin dimers in toluene solution and in several self-assembled prismatic
      structures are described. The butadiyne linkage between the 20-positions of the
      macrocycles results in new electronic transitions polarized along the long axes
      of the dimers. These transitions greatly increase the ability of these dimers to
      absorb the solar spectrum over a broad wavelength range. Femtosecond transient
      absorption spectroscopy reveals the relative rate of rotation of the macrocycles
      around the butadiyne bond joining them. Following addition of 3-fold symmetric,
      metal-coordinating ligands, both macrocyclic dimers self-assemble into prismatic
      structures in which the dimers comprise the faces of the prisms. These structures
      were confirmed by small-angle X-ray scattering experiments in solution using a
      synchrotron source. Photoexcitation of the prismatic assemblies reveals that
      efficient, through-space energy transfer occurs between the macrocyclic dimers
      within the prisms. The distance dependence of energy transfer between the faces
      of the prisms was observed by varying the size of the prismatic assemblies
      through the use of 3-fold symmetric ligands having arms with different lengths.
      These results show that self-assembly of discrete macrocyclic prisms provides a
      useful new strategy for controlling singlet exciton flow in antenna systems for
      artificial photosynthesis and solar cell applications.

PMID- 18327919
TI  - High-energy polarized-beam energy-dispersive X-ray fluorescence analysis combined
      with activated thin layers for cadmium determination at trace levels in complex
      environmental liquid samples.
AB  - In this paper, we describe a new method for trace level Cd determination in
      complex environmental liquid samples. Thin layers activated with the extractant
      Aliquat 336 were prepared either by direct impregnation of commercial polymeric
      supports or by physical inclusion in a cellulose triacetate matrix, and both were
      effectively used to collect Cd present at low concentration in different aqueous
      matrixes. Quantitation of Cd contained in the thin layers was performed by high
      energy polarized-beam energy-dispersive X-ray fluorescence. The effects of
      various experimental parameters such as layer composition, equilibration time,
      and instrumental conditions have been investigated. The analysis of different
      impregnated layers contacted with solutions ranging from 5 to 8000 microg L-1 Cd
      showed a linear response between the Cd concentration in the aqueous solutions
      and the metal present in the thin layer, with a detection limit of 0.7 microg L
      1. The accuracy of the proposed method was confirmed by analyzing spiked seawater
      samples and a synthetic water sample containing, besides Cd, high amounts of
      other metal pollutants such as Ni, Cu, and Pb. The attained results were
      comparable to those obtained by anodic stripping voltammetry or inductively
      coupled plasma spectrometry.

PMID- 18327920
TI  - Prediction of analyte retention for ion chromatography separations performed
      using elution profiles comprising multiple isocratic and gradient steps.
AB  - This study addresses the simulation of ion chromatographic (IC) separations
      performed under conditions where the elution profile consists of a sequence of
      isocratic and gradient elution steps (referred to as "complex elution profiles").
      First, models for prediction of retention under gradient elution conditions in IC
      were evaluated using an extensive database of gradient elution retention data. It
      is shown that one such model is preferred on the basis that it can be used to
      predict gradient retention times on the basis of isocratic input data. A method
      is then proposed for using this model for complex elution profiles whereby each
      step of the elution profile is treated separately and analyte movement through
      the column is mapped. An empirically based algorithm for predicting peak width
      under complex elution conditions is also proposed. Evaluation of the suggested
      approaches was undertaken on a set of 24 analyte anions and 13 analyte cations on
      5 different Dionex columns using a range of 5-step complex elution profiles that
      gave R2 values for correlations between predicted and observed retention times of
      0.987 for anions and 0.997 for cations. The simulation of separations of anions
      and cations using a 3-step complex elution profile is demonstrated, with good
      correlation between observed and predicted chromatograms. The proposed approach
      is useful for the rapid development of separations when complex elution profiles
      are used in IC.

PMID- 18327921
TI  - Combined analysis of C-18 unsaturated fatty acids using natural abundance
      deuterium 2D NMR spectroscopy in chiral oriented solvents.
AB  - The quantitative determination of isotopic (2H/1H)i ratios at natural abundance
      using the SNIF-NMR protocol is a well-known method for understanding the
      enzymatic biosynthesis of metabolites. However, this approach is not always
      successful for analyzing large solutes and, specifically, is inadequate for
      prochiral molecules such as complete essential unsaturated fatty acids. To
      overcome these analytical limitations, we use the natural abundance deuterium 2D
      NMR (NAD 2D NMR) spectroscopy on solutes embedded in polypeptide chiral liquid
      crystals. This approach, recently explored for measuring (2H/1H)i ratios of small
      analytes (Lesot, P.; Aroulanda, C.; Billault, I. Anal. Chem. 2004, 76, 2827
      2835), is a powerful way to separate the 2H signals of all nonequivalent
      enantioisotopomers on the basis both of the 2H quadrupolar interactions and of
      the 2H chemical shift. Two significant advances over our previous work are
      presented here and allow the complete isotopic analysis of four mono- and
      polyunsaturated fatty acid methyl esters: methyl oleate (1), methyl linoleate
      (2), methyl linolenate (3), and methyl vernoleate (4). The first consists of
      using NMR spectrometers operating at higher magnetic field strength (14.1 T) and
      equipped with a selective cryoprobe optimized for deuterium nuclei. The second is
      the development of Q-COSY Fz 2D NMR experiments able to produce phased 2H 2D maps
      after a double Fourier transformation. This combination of modern hardware and
      efficient NMR sequences provides a unique tool to analyze the (2H/1H)i ratios of
      large prochiral molecules (C-18) dissolved in organic solutions of poly(gamma
      benzyl-L-glutamate) and requires smaller amounts of solute than previous study on
      fatty acids. For each compound (1-4), all 2H quadrupolar doublets visible in the
      2D spectra have been assigned on the basis of 2H chemical shifts, isotopic data
      obtained from isotropic quantitative NAD NMR, and by an interspectral comparison
      of the anisotropic NAD spectra of four fatty acids. The NMR results are discussed
      in terms of (2H/1H)i isotopic distribution and molecular orientation in the
      mesophase. For the first time, we show that the investigation of natural isotopic
      fractionation of complete fatty acids is possible without the need of chemical
      modifications, hence providing an alternative method to probe the mechanisms of
      enzymes implied in the biosynthetic pathway of unsaturated fatty acids.

PMID- 18327922
TI  - Theoretical studies of carbocations in ion pairs. 8. Search for anchimeric
      assistance in the ionization of 2-butyl cation precursors.
AB  - The structures of carbocations formed in the ionization of 2-butyl precursors
      were investigated by high level ab initio MO calculations on the reaction of 2
      butyl fluoride (1) with borane, which gives a C4H9+ cation paired with
      trihydrofluoroborate (FBH3-, A). Two conformations of the "open," secondary
      cation (2) in the ion pair resulted from two conformations of 1, with F gauche
      and trans to C4 (2-g and 2-t, respectively). No anchimeric assistance by hydrogen
      (in 1-g) or methyl (in 1-t) was evidenced. In fact, attempts at optimizing the
      geometry of the H-bridged (3) and methyl-bridged (6) cations at short interionic
      distances (d) led to the corresponding conformations of 2. Upon ion separation,
      proton transfer from 2 to the anion occurred at intermediate interionic
      distances, consonant with experimental observations in trifluoroacetic acid.
      Elimination was prevented by addition of a lithium cation to the ion pair, i.e.,
      running computations on triple ions (2.A.Li+). Cation 6 became an energy minimum
      beyond d = 2.5 A and 3 beyond 2.8 A. Cation 2-g was still the most stable isomer
      at d = 3.2 A, which was greater than the interionic distance in the crystals of
      the isomeric tert-butyl cation salts (3-3.1 A). Thus, spectral determinations of
      2-butyl cations in the solid state should be interpreted with 2-g as the main
      component of the ion mixture. When the ions became separated (d >/= 4 A), only
      the bridged ions were energy minima. In this process, bridging did not occur
      opposite to the leaving group to assist the ionization, but on the same side with
      it, being controlled by the electrostatic interaction with the anion, as it
      departed from the vicinity of the cation. Such behavior was also noted in the
      ionization of the 3-methyl-2-butyl homolog.

PMID- 18327923
TI  - Magnetic interactions in alkyl substituted cyclohexane diradical systems: a
      broken symmetry approach.
AB  - Magnetic interactions in alkyl substituted cyclohexane diradical systems have
      been investigated within the framework of spin flip density functional theory.
      The investigations suggest a ferromagnetic interaction for both the alkyl
      substituted cyclohexane-1,3-diyls and cyclohexane-1,4-diyls. However, in the case
      of cyclohexane-1,3-diyls, the ferromagnetic interaction is much stronger than its
      1,4 analogue. Interestingly, it has been observed that this interaction is
      reduced to almost half the value from the butyl to the decyl substituted unit
      relative to the lower homologues up to the propyl substituted unit in cyclohexane
      1,3-diyls. On the other hand, in case of alkyl substituted cyclohexane-1,4-diyls,
      the ferromagnetic interaction for the higher homologues, i.e., butyl to decyl
      substituted units, substantially reduces to almost 5-6 times the value of its
      lower homologue (methyl and ethyl substituted unit). In both these cyclohexane
      diradical systems, beyond butyl substituted unit, a saturation effect in the
      magnetic coupling constant (J) value is observed. The rapid decrease followed by
      a saturation in the singlet-triplet gap and J as well may be explained by
      considering positive inductive effect of the alkyl substituent.

PMID- 18327924
TI  - Analyzing nonexponential kinetics with multiple population-period transient
      spectroscopy (MUPPETS).
AB  - A new multidimensional spectroscopy (MUPPETS) was recently introduced (van
      Veldhoven, E.; et al. ChemPhysChem 2007, 8, 1761) that distinguishes between
      nonexponential relaxations that are due to heterogeneous dynamics and those that
      are due to homogeneous dynamics. This paper develops methods for the quantitative
      analysis of MUPPETS data and demonstrates the ability of this experiment to
      decompose a complex decay into its components. These methods have been applied to
      MUPPETS data on the ground-state recovery of auramine in methanol and on a
      mixture of auramine and coumarin 102 in methanol. The auramine is found to have
      two kinetically different components, even though the decay times are too similar
      to be distinguished in a one-dimensional experiment. The dynamics of each
      component are derived from the MUPPETS data in a model-free procedure in
      particular without assuming that the individual decays are exponential or that
      they have similar shapes. In fact, the component decays are each found to be
      nonexponential and to have different decay shapes. We suggest that the two
      components are due to ion-paired and nonpaired molecules. The effect of rotation
      on MUPPETS with all parallel polarizations is analyzed. The nonexponentiality in
      ground-state recovery signals due to the combination of rotation and population
      decay is shown to behave as a nearly ideal homogeneous nonexponentiality. This
      prediction is confirmed in a mixture of auramine and coumarin. MUPPETS allows the
      decay from the fast relaxing auramine to be removed from the mixture, leaving
      only the rotation/population decay of the coumarin.

PMID- 18327925
TI  - Photofragmentation of closo-carboranes part 1: Energetics of decomposition.
AB  - The ionic fragmentation following B 1s and C 1s excitation of three isomeric
      carborane cage compounds [closo-dicarbadodecaboranes: orthocarborane (1,2
      C2B10H12), metacarborane (1,7-C2B10H12), and paracarborane (1,12-C2B10H12)] is
      compared with the energetics of decomposition. The fragmentation yields for all
      three molecules are quite similar. Thermodynamic cycles are constructed for
      neutral and ionic species in an attempt to systemically characterize single-ion
      closo-carborane creation and fragmentation processes. Lower energy decomposition
      processes are favored. Among the ionic species, the photon-induced decomposition
      is dominated by BH+ and BH2(+) fragment loss. Changes in ion yield associated
      with core to bound excitations are observed.

PMID- 18327926
TI  - Microhydration of NO3(-): a theoretical study on structure, stability and IR
      spectra.
AB  - A systematic study on the structure and stability of nitrate anion hydrated
      clusters, NO3(-) x n H2O (n = 1-8) are carried out by applying first principle
      electronic structure methods. Several possible initial structures are considered
      for each size cluster to locate equilibrium geometry by applying a correlated
      hybrid density functional with 6-311++G(d,p) basis function. Three different
      types of arrangements, namely, symmetrical double hydrogen bonding, single
      hydrogen bonding and inter-water hydrogen bonding are obtained in these hydrated
      clusters. A structure having inter-water hydrogen bonding is more stable compared
      to other arrangements. Surface structures are predicted to be more stable over
      interior structures. Up to five solvent H2O molecules can stay around solute NO3(
      ) anion in structures having an inter-water hydrogen-bonded cyclic network. A
      linear correlation is obtained for weighted average solvent stabilization energy
      with the size (n) of the hydrated cluster. Distinctly different shifts of IR
      bands are observed in these hydrated clusters for different kinds of bonding
      environments of O-H and N=O stretching modes compared to isolated H2O and NO3(-)
      anion. Weighted average IR spectra are calculated on the basis of statistical
      population of individual configurations of each size cluster at 150 K.

PMID- 18327927
TI  - Reaction dynamics of phenyl radicals (C6H5) with propylene (CH3CHCH2) and its
      deuterated isotopologues.
AB  - The reactions between phenyl radicals (C6H5) and propylene (CH3CHCH2) together
      with its D6- and two D3-isotopologues were studied under single collision
      conditions using the crossed molecular beams technique. The chemical dynamics
      inferred from the center-of-mass translational and angular distributions suggests
      that the reactions are indirect and initiated by an addition of the phenyl
      radical to the alpha-carbon atom (C1 carbon atom) of the propylene molecule at
      the =CH2 unit to form a radical intermediate (CH3CHCH2C6H5) on the doublet
      surface. Investigations with D6-propylene specified that only a deuterium atom
      was emitted; the phenyl group was found to stay intact. Studies with 1,1,2-D3-
      and 3,3,3-D3-propylene indicated that the initial collision complexes
      CH3CDCD2C6H5 (from 1,1,2-D3-propylene) and CD3CHCH2C6H5 (from 3,3,3-D3-propylene)
      eject both a hydrogen atom via rather loose exit transition states to form the D3
      isotopomers of cis/trans-1-phenylpropene (CH3CHCHC6H5) (80-90%) and 3
      phenylpropene (H2CCHCH2C6H5) (10-20%), respectively. Implications of these
      findings for the formation of polycyclic aromatic hydrocarbons (PAHs) and their
      precursors in combustion flames are discussed.

PMID- 18327928
TI  - Resonance Raman scattering of rhodamine 6G as calculated by time-dependent
      density functional theory: vibronic and solvent effects.
AB  - The geometries, UV-vis absorption spectra, and resonance Raman (RR) intensities
      have been determined for the S1 and S3 excited states of rhodamine 6G (R6G) in
      vacuum and ethanol by means of DFT/TDDFT methodologies with the aim of better
      understanding the structures and properties of the excited states. The RR spectra
      have been simulated from the vibronic theory of RR scattering as well as within
      the short-time approximation, while the solvent effects have been modeled using
      the polarizable continuum model. The S1 and S3 states of R6G present UV-vis
      absorption bands with similar vibronic structure, i.e., a shoulder at smaller
      wavelengths, although this shoulder is relatively more intense and more sensitive
      to the solvent in the case of S3. These differences are corroborated by the
      larger geometry relaxations upon excitation for S3 and the fact that the charge
      transfer of S3 is reduced in ethanol. Moreover, the differences between S1 and S3
      are magnified when considering the RR spectra. On one hand, the RR spectrum of
      R6G in resonance with the S0 --> S1 transition presents many transitions of which
      the relative intensities strongly vary when the excitation wavelength gets closer
      to the maximum of absorption. The RR spectrum of R6G in resonance with S1 is
      however little influenced by the solvent. On the other hand, the RR spectrum of
      R6G in resonance with the S0 --> S3 transition displays only a few bands,
      strongly depends on the solvent, and is little affected when changing the
      excitation wavelength within the limits of the absorption band. As a consequence,
      the short-time approximation is suitable to reproduce the RR spectrum of R6G in
      resonance with S3 for a broad range of excitation wavelengths, whereas the
      vibronic theory approach is needed for describing the RR spectrum of R6G in
      resonance with S1 close to resonance.

PMID- 18327929
TI  - Unbinding of nicotine from the acetylcholine binding protein: steered molecular
      dynamics simulations.
AB  - The ligand binding/unbinding process is critical to our understanding of the
      pharmacology of both the nicotinic acetylcholine receptor (nAChR) and the
      acetylcholine binding protein (AChBP). Steered molecular dynamics simulations
      were performed to learn about the unbinding process of the full agonist nicotine.
      Three different pulling models were designed to investigate the possible
      binding/unbinding pathways: radial and tangent models, and also a mixed model. Of
      the three, the tangent pulling model finally failed to dissociate nicotine from
      the ligand binding pocket. The efficiency of the pulling force profiles was
      superior, and the opening of the C-loop was smaller in the mixed pulling model
      than that in the radial model. The most favorable pathway for the cholinergic
      agonist nicotine to enter or leave the binding pocket is through the principal
      binding side, following a curvilinear track. Noticeably, it has been seen that
      the unbinding of the nicotine is concomitant with a global rotation of the
      protein-ligand complex which could be caused by the interactions of the ligand
      with protein at the tangent direction.

PMID- 18327930
TI  - Length-dependent optical effects in single walled carbon nanotubes.
AB  - Recently, Heller et al. reported length-dependent effects on the relative
      photoluminescence (PL) quantum yield of single walled carbon nanotubes (SWNTs)
      [Heller et al J. Am. Chem. Soc. 2004, 126, 14567-14573]. We propose a simple
      model involving thermal diffusion of excitons along the nanotube axis and
      quenching at the ends, to explain the observed trend in their data. By fitting to
      our model, we extract a diffusion coefficient of 6 cm(2)/s for excitons in SWNTs.
      Assuming a mono exponential decay of exciton PL, we also predict that effective
      length-dependent PL lifetimes for these excitons lie in the range of 1-27 ps.
      Experimental observations are shown to be consistent with stochastic rather than
      wavepacket-like exciton migration, which is in agreement with ultrafast excitonic
      dephasing. Edge effects seem to limit the use of short SWNTs in imaging and
      optical sensing applications.

PMID- 18327931
TI  - First-principles free-energy analysis of helix stability: the origin of the low
      entropy in pi helices.
AB  - The temperature dependence of the stability of infinite poly-L-alanine alpha, pi,
      and 310 helices with respect to the fully extended structure (FES) is calculated
      using density functional theory and the harmonic approximation. We find that the
      vibrational entropy strongly reduces the stability of the helical conformations
      with respect to the FES. By mapping the ab initio data on an approximate
      mechanical model, we show that this effect is exclusively due to the formation of
      hydrogen bonds, whereas changes in the backbone stiffness are practically
      negligible. We furthermore observe that the temperature dependence is largest for
      the pi helix and smallest for the 310 helix and demonstrate that these trends are
      a generic behavior related to the geometric peculiarities of the respective
      helical conformations and independent of the specific amino acid sequence.

PMID- 18327932
TI  - Temporal evolution of an electron-free afterglow in the pulsed plasma
      polymerisation of acrylic acid.
AB  - By use of time and energy-resolved mass spectrometry, negative ions with masses
      ranging from m/z = 1-287 amu have been observed in the afterglow of a low
      pressure (10 mTorr) pulsed acrylic acid polymerizing plasma. The most intense
      peaks, seen at m/z = 71, 143, 215, and 287, are assigned to the dehydrogenated
      oligomer of the form [nM-H](-) for n = 1, 2, 3, and 4, respectively. The results
      strongly suggest that both m/z = 71 and 143 ions are produced in the on period of
      the pulse cycle (0.1 ms duration), with higher masses m/z = 215 and 287 being
      produced by neutral ion chemistry in the off period (up to 40 ms in duration).
      The increase in the intensity of the [3M-H](-) and [4M-H](-) peaks in the off
      period is accompanied by a rapid fall in the concentration of [M-H]- ions and
      electrons, the latter decreasing from approximately 10(15) m(-3) to zero within
      150 micros. Deep into the afterglow, Langmuir probe measurements show that the
      charge species only consist of positive and negative ions, present at equal
      concentrations in excess of approximately 10(14) m(-3) even after 10 ms that is,
      the plasma is wholly electron free. To describe the growth of large negative ions
      a number of possible ion-neutral chemical pathways have been postulated, and a
      calculation of the ambipolar diffusion rates to the walls suggests that, in the
      off period, the positive and negative ion contribution to the deposition rate is
      small ( approximately 1%) compared to the net total deposition rate. However, the
      observations do indicate that it may be necessary to update models of film growth
      in the pulsed plasma polymerization of acrylic acid to account for negative ions.

PMID- 18327933
TI  - D-alaninol adsorption on Cu(100): photoelectron spectroscopy and first-principles
      calculations.
AB  - The adsorption of a single molecule of the D-enantiomer of alaninol (2-amino-1
      propanol) on the surface of Cu(100) is investigated through density functional
      theory calculations. Different possible adsorption sites for D-alaninol are
      tested, and it is found that the most stable configuration presents both amino
      and hydroxyl group covalently interacting with "on top" copper atoms. The
      electronic structure is analyzed in detail and compared with experimental
      photoelectron spectra. Another adsorption structure in which a dehydrogenation
      process is assumed to occur on the amino group is analyzed and provides a
      possible explanation of the valence band electronic structure and of the
      experimentally observed N 1s core-level shift at full coverage, where a self
      assembled ordered chiral monolayer is formed on the copper surface.

PMID- 18327934
TI  - Mesomorphic structures of protonated surfactant-encapsulated polyoxometalate
      complexes.
AB  - Keggin-type heteropolyanions, H(3)PW(12)O(40) (HPW), Na(3)PW(12)O(40) (NaPW),
      H(4)SiW(12)O(40) (HSiW) and K(4)SiW(12)O(40) (KSiW), were encapsulated by a
      cationic surfactant, di[12-(4'-octyloxy-4-azophenyl)dodecyloxy]dimethylam monium
      bromide (L), through the replacement of counterions. The resulting surfactant
      encapsulated polyoxometalate complexes were characterized by UV-vis, Raman, and
      NMR spectra in detail. The measurement results indicated that some azobenzene
      groups of the surfactant were protonated in the complexes HL/HPW (HL is the
      abbreviation of the protonated surfactant), HL/NaPW, and HL/HSiW during the
      process of encapsulation, whereas the protonation was not observed in L/KSiW. The
      thermotropic liquid crystal properties of these complexes were investigated by
      differential scanning calorimetry, polarized optical microscopy and variable
      temperature X-ray diffraction. Interestingly, different smectic mesophases were
      observed between the protonated HL/HSiW and the non-protonated L/KSiW, which
      suggests that the protonation of azobenzene groups in HL/HSiW plays a key role in
      the liquid crystalline organization. However, protonated HL/HPW and HL/NaPW
      exhibit a similar smectic B phase to that of the de-protonated one, L/HPW. A
      competitive balance between the phase separation and the volume minimization of
      surfactants was proposed to explain the self-organized liquid crystal structures
      of these protonated and non-protonated complexes. To the best of our knowledge,
      the present investigation provides a specific example for protonated hybrid
      materials with stable liquid crystal properties.

PMID- 18327935
TI  - Gas-phase C-H and N-H bond activation by a high valent nitrido-iron dication and
      NH-transfer to activated olefins.
AB  - A tetrapodal pentadentate nitrogen ligand (2,6-bis(1,1
      di(aminomethyl)ethyl)pyridine, 1) is used for the synthesis of the azido
      iron(III) complex [(1)Fe(N3)]X2 where X is either Br or PF6. By means of
      electrospray ionization mass spectrometry, the dication [(1)Fe(N3)]2+ can be
      transferred into the gas phase as an intact entity. Upon collisional activation,
      [(1)Fe(N3)]2+ undergoes an expulsion of molecular nitrogen to afford the
      dicationic nitrido-iron species [(1)FeN]2+ as an intermediate, which upon further
      activation can intramolecularly activate C-H- and N-H bonds of the chelating
      ligand 1 or can transfer an NH unit in bimolecular reactions with activated
      olefins. The precursor dication [(1)Fe(N3)]2+, the resulting nitrido species
      [(1)FeN]2+, and its possible isomers are investigated by mass spectrometric
      experiments, isotopic labeling, and complementary computational studies using
      density functional theory.

PMID- 18327937
TI  - Stereochemical nonrigidity of a chiral rhodium boryl hydride complex: a sigma
      borane complex as transition state for isomerization.
AB  - Experimental and computational studies are reported on half-sandwich rhodium
      complexes that undergo B-H bond activation with pinacolborane (HBpin =
      HB(OCMe2CMe2O)). The photochemical reaction of [Rh(eta5-C5H5)(R,R
      phospholane)(C2H4)] 3 (phospholane = PhP(CHMeCH2CH2CHMe)) with HBpin generates
      the boryl hydride in two distinguishable isomers [(SRh)-Rh(eta5
      C5H5)(Bpin)(H)(R,R-phospholane)] 5a and [(RRh)-Rh(eta5-C5H5)(Bpin)(H)(R,R
      phospholane)] 5b that undergo intramolecular exchange. The presence of a chiral
      phosphine allowed the determination of the interconversion rates (epimerization)
      by 1D 1H EXSY spectroscopy in C6D6 solution yielding DeltaH = 83.4 +/- 1.8 kJ mol
      1 for conversion of 5a to 5b and 79.1 +/- 1.4 kJ mol-1 for 5b to 5a.
      Computational analysis yielded gas-phase energy barriers of 96.4 kJ mol-1
      determined at the density functional theory (DFT, B3PW91) level for a model with
      PMe3 and B(OCH2CH2O) ligands; higher level calculations (MPW2PLYP) on an
      optimized QM/MM(ONIOM) geometry for the full system place the transition state
      76.8 kJ mol-1 above the average energy of the two isomers. The calculations
      indicate that the exchange proceeds via a transition state with a sigma-B-H
      bonded borane. The B-H bond lies in a mirror plane containing rhodium and
      phosphorus. No intermediate with an eta2-B-H ligand is detected either by
      experiment or calculation. Complex 3 has also been converted to the [Rh(eta5
      C5H5)Br2(R,R-phospholane)] (characterized crystallographically) and [Rh(eta5
      C5H5)(H)2(R,R-phospholane)]. The latter exhibits two inequivalent hydride
      resonances that undergo exchange with DeltaH = 101 +/- 2 kJ mol-1. DFT
      calculations indicate that the boryl hydride complex has a lower exchange barrier
      than the dihydride complex because of steric hindrance between the phospholane
      and Bpin ligands in the boryl hydride.

PMID- 18327938
TI  - Small-molecule fluorophores to detect cell-state switching in the context of high
      throughput screening.
AB  - A small molecule capable of distinguishing the distinct states resulting from
      cellular differentiation would be of enormous value, for example, in efforts
      aimed at regenerative medicine. We screened a collection of fluorescent small
      molecules for the ability to distinguish the differentiated state of a mouse
      skeletal muscle cell line. High-throughput fluorescence-based screening of C2C12
      myoblasts and myotubes resulted in the identification of six compounds with the
      desired selectivity, which was confirmed by high-content screening in the same
      cell states. The compound that resulted in the greatest fluorescence intensity
      difference between the cell states was used as the screening agent in a pilot
      screen of 84 kinase inhibitors, each present in four doses, for inhibition of
      myogenesis. Of the kinase inhibitors, 17 resulted in reduction of fluorescence at
      one or more concentrations; among the "hits" included known inhibitors of
      myogenesis, confirming that this compound is capable of detecting the
      differentiated myotube state. We suggest that the strategy of screening for
      screening agents reported here may be extended more broadly in the future.

PMID- 18327939
TI  - 2,3,5,6-Tetrafluorophenylnitren-4-yl: electron paramagnetic resonance
      spectroscopic characterization of a quartet-ground-state nitreno radical.
AB  - 2,3,5,6-Tetrafluorophenylnitren-4-yl (5) was synthesized in argon at 4 K via the
      photolysis of 2,3,5,6-tetrafluoro-4-iodo-phenyl azide (6). Electron paramagnetic
      resonance (EPR) spectroscopy allows us to observe triradical 5 in its quartet
      state with the zero-field splitting (ZFS) parameters |D/hc| = 0.285 and |E/hc| =
      0.043 cm-1. The quartet ground state of 5 is in accordance with our previous
      infrared (IR) spectroscopic investigation, in which the high-spin quartet state,
      but no low-spin doublet state, of 5 was observed in solid argon at 4 K [Wenk, H.
      H.; Sander, W. Angew. Chem., Int. Ed. 2002, 41, 2742-2745]. Because annealing of
      the matrix at temperatures of >10 K results in the rapid recombination of the
      highly reactive species 5 with I atoms produced during the photolysis of 6, the
      Curie-Weiss behavior could not be investigated. However, the absence of low-spin
      states in the IR investigations, as well as the results of ab initio and density
      functional theory (DFT) calculations, strongly suggest that 5 has a robust
      quartet ground state that is best-described as an unprecedented sigma,sigma,pi
      triradical. The ZFS of 5 has been successfully reproduced by DFT calculations,
      which furthermore provide qualitative insight into the origin of the observed EPR
      parameters.

PMID- 18327940
TI  - Screening of pi-basic naphthalene and anthracene amplifiers for pi-acidic
      synthetic pore sensors.
AB  - Synthetic ion channels and pores attract current attention as multicomponent
      sensors in complex matrixes. This application requires the availability of
      reactive signal amplifiers that covalently capture analytes and drag them into
      the pore. pi-Basic 1,5-dialkoxynaphthalenes (1,5-DAN) are attractive amplifiers
      because aromatic electron donor-acceptor (AEDA) interactions account for their
      recognition within pi-acidic naphthalenediimide (NDI) rich synthetic pores.
      Focusing on amplifier design, we report here the synthesis of a complete
      collection of DAN and dialkoxyanthracene amplifiers, determine their oxidation
      potentials by cyclic voltammetry, and calculate their quadrupole moments.
      Blockage experiments reveal that subtle structural changes in regioisomeric DAN
      amplifiers can be registered within NDI pores. Frontier orbital overlap in AEDA
      complexes, oxidation potentials, and, to a lesser extent, quadrupole moments are
      shown to contribute to isomer recognition by synthetic pores. Particularly
      important with regard to practical applications of synthetic pores as
      multianalyte sensors, we further demonstrate that application of the lessons
      learned with DAN regioisomers to the expansion to dialkoxyanthracenes provides
      access to privileged amplifiers with submicromolar activity.

PMID- 18327941
TI  - Light harvesting in photosystem II core complexes is limited by the transfer to
      the trap: can the core complex turn into a photoprotective mode?
AB  - A structure-based modeling and analysis of the primary photophysical reactions in
      photosystem II (PS-II) core complexes is presented. The modeling is based on a
      description of stationary and time-resolved optical spectra of the CP43, CP47,
      and D1-D2-cytb559 subunits and whole core complexes. It shows that the decay of
      excited states in PS-II core complexes with functional (open) reaction centers
      (RCs) is limited by the excitation energy transfer from the CP43 and CP47 core
      antennae to the RC occurring with a time constant of 40-50 ps at room
      temperature. The chlorophylls responsible for the low energy absorbance bands in
      the CP43 and CP47 subunits are assigned, and their signatures in hole burning,
      fluorescence line narrowing, and triplet-minus-singlet spectra are explained. The
      different locations of these trap states in the CP43 and CP47 antennae with
      respect to the reaction center lead to a dramatic change of the transfer dynamics
      at low temperatures. The calculations predict that, compared to room temperature,
      the fluorescence decay at 77 K should reveal a faster transfer from CP43 and a
      much slower and highly dispersive transfer from CP47 to the RC. A factor of 3
      increase in the fastest decay time constant of fluorescence that was reported to
      occur when the RC is closed (the plastoquinone QA is reduced) is understood in
      the present model by assuming that the intrinsic rate constant for primary
      electron transfer decreases from 100 fs-1 for open RCs to 6 ps-1 for closed RCs,
      leading to a reduction of the primary electron acceptor PheoD1, in 300 fs and 18
      ps, respectively. The model suggests that the reduced QA switches the photosystem
      into a photoprotective mode in which a large part of the excitation energy of the
      RC returns to the CP43 and CP47 core antennae, where the physiologically
      dangerous triplet energy of the chlorophylls can be quenched by the carotenoids.
      Experiments are suggested to test this hypothesis. The ultrafast primary electron
      transfer inferred for open RCs provides further support for the accessory
      chlorophyll ChlD1 to be the primary electron donor in photosystem II.

PMID- 18327942
TI  - Scope and mechanism of formal S(N)2' substitution reactions of a monomeric
      imidozirconium complex with allylic electrophiles.
AB  - The zirconium imido complex Cp2(THF)Zr=NSi(t-Bu)Me2 (1) reacts with allylic
      ethers, chlorides, and bromides to give exclusively the products of the SN2'
      reaction; i.e., attack at the allylic position remote from the leaving group with
      migration of the double bond. The primary amine products can be isolated in
      excellent yields, after in situ Cbz protection, in the presence of variety of
      functional groups. Good diastereoselectivity and complete stereoselectivity
      allowed the formation of enantioenriched allylic amines from enantioenriched
      allylic ethers. Regiospecific substitution with 1 has also been achieved with
      allylic fluorides, which are notoriously poor substrates in other substitution
      reactions. On the basis of rate and kinetic isotope effect studies, we propose a
      general mechanism for the allylic substitution reactions with 1 which involves
      dissociation of THF and binding of the substrate, followed by the substitution
      step. In a DFT study of the substitution reaction, we identified a six-membered
      closed transition state for the substitution step and other relevant stationary
      points along the reaction coordinate. This study shows that the substitution
      reaction can be described as a concerted asynchronous [3,3]-sigmatropic
      rearrangement. This detailed knowledge of the reaction mechanism provides a
      rationale for the origins of the observed regio-, diastereo-, and
      stereoselectivity and of the unusual reactivity profile observed in the reaction.

PMID- 18327943
TI  - Synthesis of B/Si bidentate Lewis acids, o-(Fluorosilyl)(dimesitylboryl)benzenes,
      and their fluoride ion affinity.
AB  - o-(Fluorosilyl)(dimesitylboryl)benzenes have been prepared as colorless crystals
      by reacting fluorodimesitylborane with o-(fluorodimethylsilyl)phenyllithium and o
      (fluorodiphenylsilyl)phenyllithium. The o-(fluorosilyl)(dimesitylboryl)benzenes
      serve as B/Si bidentate Lewis acid and efficiently capture fluoride ion from
      potassium fluoride in the presence of [2.2.2]cryptand or 18-crown-6 in toluene,
      giving the corresponding mu-fluoro bridged products. The structures were
      characterized by X-ray crystal structure analysis and multinuclear NMR
      spectroscopy. Fluoride ion affinities of the o
      (fluorosilyl)(dimesitylboryl)benzenes were evaluated in comparison with non
      silylated triarylborane.

PMID- 18327944
TI  - Gold-catalyzed cycloisomerization of 1,5-allenynes via dual activation of an ene
      reaction.
AB  - Tris(triphenylphosphinegold) oxonium tetrafluoroborate, [(Ph3PAu)3O]BF4,
      catalyzes the rearrangement of 1,5-allenynes to produce cross-conjugated trienes.
      Experimental and computational evidence shows that the ene reaction proceeds
      through a unique nucleophilic addition of an allene double bond to a cationic
      phosphinegold(I)-complexed phosphinegold(I) acetylide, followed by a 1,5-hydrogen
      shift.

PMID- 18327945
TI  - Nanostructured AgPb(m)SbTe(m+2) system bulk materials with enhanced
      thermoelectric performance.
AB  - Nanostructured Ag0.8Pbm+xSbTem+2 (m = 18, x = 4.5) system thermoelectric
      materials have been fabricated by combining mechanical alloying (MA) and spark
      plasma sintering (SPS) methods followed by annealing for several days to
      investigate the effect on microstructure and thermoelectric performance. It was
      found that appropriate annealing treatment could reduce both the electrical
      resistivity and the thermal conductivity at the same time, consequently greatly
      enhancing the thermoelectric performance. A low electrical resistivity of 2 x 10
      3 Ohm-cm and low thermal conductivity of 0.89 W m-1 K-1 were obtained for the
      sample annealed for 30 days at 700 K. The very low thermal conductivity is
      supposed to be due to the nanoscopic Ag/Sb-rich regions embedded in the matrix. A
      high ZT value of 1.5 at 700 K has been achieved for the sample annealed for 30
      days.

PMID- 18327946
TI  - "Fatal adsorption" of brushlike macromolecules: high sensitivity of C-C bond
      cleavage rates to substrate surface energy.
AB  - Adsorption-induced degradation of brushlike macromolecules was monitored through
      molecular imaging by atomic force microscopy. The rate constant for C-C bond
      cleavage was shown to be extremely sensitive to the substrate surface energy. A
      few percent increase in the surface energy from 69.2 to 71.2 mN/m led to an order
      of magnitude increase of the scission rate. The absolute values of the rupture
      forces ranging from 2.57 to 2.47 nN are in agreement with previously calculated
      and measured values for stretching surface-tethered molecules.

PMID- 18327947
TI  - Stoichiometric and homogeneous-catalytic diboration of the n=n double bond of
      azobenzene.
AB  - The diboration of the N=N double bond of azobenzene was achieved by reaction of
      the [3]diboraplatinametalloarenophanes derived from ferrocene, [Fe(eta5
      C5H4)B(NMe2)Pt(PEt3)2B(NMe2)(eta5-C5H4)], and bis(benzene)chromium, [Cr(eta6
      C6H5)B(NMe2)Pt(PEt3)2B(NMe2)(eta6-C6H5)], with an excess of azobenzene in toluene
      at elevated temperature. The formation of the anticipated ansa
      bis(boryl)hydrazines was substantiated by the determination of the molecular
      structure of the chromium derivative by X-ray diffraction. The synthesis of the
      ansa-bis(boryl)hydrazine derivative of ferrocene could also be accomplished under
      homogeneous catalysis conditions. Hence, reaction of the well-known
      [2]boraferrocenophane, [Fe(eta5-C5H4)2B2(NMe2)2], and azobenzene in the presence
      of 5 mol % [Pt(PEt3)3] afforded the bis-borylated hydrazine derivative in good
      yields.

PMID- 18327948
TI  - Carboxylation of an ansa-zirconocene dinitrogen complex: regiospecific hydrazine
      synthesis from N2 and CO2.
AB  - Addition of 2 equiv of carbon dioxide to the ansa-zirconocene dinitrogen complex
      resulted in selective insertion into each zirconium nitrogen bond, forming a C2
      symmetric dicarboxylated diazenido compound. Treatment with excess Me3SiI
      furnished the ansa-zirconocene diiodide along with the N,N'-dicarboxylated
      silylated hydrazine. New nitrogen-carbon bonds were also assembled by addition of
      methyl triflate. Tri- and tetrasubstituted hydrazines could be formed by
      treatment with water and Me3SiI, respectively. The regiochemistry of the N2
      carboxylation is controlled by the ansa-cyclopentadienyl ligand where the
      sterically demanding tert-butyl substituents and the C2 symmetry of the dimer
      dictates the stereochemistry of CO2 insertion. These results demonstrate the
      ability of zirconium dinitrogen compounds to participate in heterocumulene
      insertion chemistry.

PMID- 18327949
TI  - Intramolecular hetero-Diels-Alder reactions of imine and iminium dienophiles:
      quantum mechanical exploration of mechanisms and stereoselectivities.
AB  - A series of intramolecular hetero-Diels-Alder reactions of iminium and imine
      dienophiles has been explored with density functional theory using the B3LYP
      functional and 6-31+G* basis set. Aqueous solvation energies were calculated with
      the CPCM method. DFT predicts that these reactions are concerted but involve
      highly asynchronous transition states. Stereochemical preferences of imine
      cycloaddition transition states arise from electron repulsion of the nitrogen
      lone pair with electron density from the butadiene moiety. Protonation of the
      nitrogen leads to a highly asynchronous transition state. The iminium dienophiles
      are predicted to have a 17 kcal/mol lower barrier than the corresponding imines,
      even in aqueous solution.

PMID- 18327950
TI  - Toward an amphiphilic bilirubin: the crystal structure of a bilirubin e-isomer.
AB  - A new bilirubinoid analog (1) with two methoxy beta-substituents on the lactam
      ring of each dipyrrinone was synthesized and examined spectroscopically. It is
      more soluble in CH3OH and CHCl3 than bilirubin, which is insoluble in CH3OH but
      soluble in CHCl3. The solubility of 1 is approximately 10 microg/mL in CH3OH (vs
      < or =1 microg/mL for bilirubin) and approximately 3 mg/mL in CHCl3 (vs
      approximately 0.6 mg/mL for bilirubin). Vapor pressure osmometry indicates that
      1, like bilirubin, is monomeric in CHCl3, and NMR studies show that the most
      stable structure has the syn-4Z,syn-15Z configuration, with the pigment's
      dipyrrinones engaged in intramolecular hydrogen bonding to the propionic acid
      carboxyl groups. And, like bilirubin, Z,Z-1 adopts a conformation that is bent in
      the middle into a ridge-tile shape. For the first time, a crystal structure of a
      bilirubin E-isomer has been obtained. Crystallization of 1 under dim room
      lighting gave an X-ray quality crystal of the anti-4E,syn-15Z-(photo) isomer, in
      which only the Z-dipyrrinone half is engaged in intramolecular hydrogen bonding
      to a propionic acid. Hydrogen bonding is nearly completely disengaged in the E
      dipyrrinone half; yet, the ridge-tile conformation persists.

PMID- 18327951
TI  - A fluorous-tagged linker from which small molecules are released by ring-closing
      metathesis.
AB  - A fluorous-tagged linker for the parallel synthesis of small- and medium-ring and
      macrocyclic nitrogen heterocycles using ring-closing metathesis is described. The
      linker was designed such that "cyclization-release" of the cyclic heterocyclic
      products was coupled with liberation of the active catalyst. The design of the
      linker was validated using a non-fluorous-tagged model. A wide range of
      unsaturated alcohols were used as reagents to functionalize a fluorous-tagged
      sulfonamide, (Z)-{N-[4-(2-(N'-3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10
      heptadecafluorodecyl)-4-methylsulfonamido)methylallyloxy]but-2-enyl}-2
      nitrobenzenesulfonamide, using Fukuyama-Mitsunobu reactions; in each case,
      fluorous-solid-phase extraction (F-SPE) was used to purify the functionalized
      linker from the excess reagents. In general, the "cyclization-release" of cyclic
      products was triggered using a light-fluorous tagged derivative of the Grubbs
      Hoveyda second-generation catalyst. After the metathesis step, F-SPE was used to
      purify released cyclic compounds from the fluorous-tagged linker and the fluorous
      tagged catalyst. The scope and limitations of the approach were determined using
      a range of substrates which probed different aspects of the functionalization and
      metathesis steps. In the study as a whole, a wide range of small- and medium-ring
      and macrocyclic nitrogen heterocycles were prepared using polyene and polyenyne
      metathesis cascades.

PMID- 18327952
TI  - Correlated rotations in benzylfluorene derivatives: structure, conformation, and
      stereodynamics.
AB  - Fluorene derivatives, having substituted benzyl groups bonded to position 9, have
      been investigated by variable temperature NMR spectroscopy. Stereodynamic
      processes involving restricted rotation about the fluorenyl-CH2 and aryl-CH2
      bonds have been observed, leading to conformers and enantiomeric forms, and the
      corresponding barriers were determined by line shape simulation. These dynamic
      processes are interpreted as being due to correlated rotation pathways, on the
      basis of DFT computations that satisfactorily reproduce the experimental
      barriers. The structures of two such compounds were also determined by single
      crystal X-ray diffraction.

PMID- 18327953
TI  - The 4-(N-dichloroacetyl-N-methylamino)benzyloxymethyl group for 2'-hydroxyl
      protection of ribonucleosides in the solid-phase synthesis of
      oligoribonucleotides.
AB  - Emerging RNA-based technologies for controlling gene expression have triggered a
      high demand for synthetic oligoribonucleotides and have motivated the development
      of ribonucleoside phosphoramidites that would exhibit coupling kinetics and
      coupling efficiencies comparable to those of deoxyribonucleoside
      phosphoramidites. To fulfill these needs, the novel 4-(N-dichloroacetyl-N
      methylamino)benzyloxymethyl group for 2'-hydroxyl protection of ribonucleoside
      phosphoramidites 9a-d has been implemented (Schemes 1 and 2). The solid-phase
      synthesis of AUCCGUAGCUAACGUCAUGG was then carried out employing 9a-d as 0.2 M
      solutions in dry MeCN and 5-benzylthio-1H-tetrazole as an activator. The coupling
      efficiency of 9a-d averaged 99% within a coupling time of 180 s. Following
      removal of all base-sensitive protecting groups, cleavage of the remaining 2'-[4
      (N-methylamino)benzyl] acetals from the RNA oligonucleotide was effected in
      buffered 0.1 M AcOH (pH 3.8) within 30 min at 90 degrees C. RP-HPLC and PAGE
      analyses of the fully deprotected AUCCGUAGCUAACGUCAUGG were comparable to those
      of a commercial RNA oligonucleotide sharing an identical sequence. Enzymatic
      digestion of the RNA oligomer catalyzed by bovine spleen phosphodiesterase and
      bacterial alkaline phosphatase revealed no significant amounts of RNA fragments
      containing (2'-->5')-internucleotidic phosphodiester linkages or noteworthy
      nucleobase modifications.

PMID- 18327954
TI  - On the thermal stability of [60]fullerene cycloadducts: retro-cycloaddition
      reaction of 2-pyrazolino[4,5:1,2][60]fullerenes.
AB  - 2-Pyrazolino[4,5:1,2][60]fullerenes undergo a thermally induced retro
      cycloaddition process whose efficiency is influenced by the nature of the C
      substituent. C-Aryl-N-Aryl-2-pyrazolino[60]fullerenes (2a-d) poorly undergo a
      thermal retro-cycloaddition reaction even in the presence of a strong
      dipolarophile or a metal Lewis acid which, in contrast to other fullerene
      derivatives, shows their remarkable thermal stability. C-Alkyl-N-Aryl-2
      pyrazolino[60]fullerenes (2e-f) show a different behavior, being more vulnerable
      to the presence of copper triflate and leading to the retro-cycloaddition product
      (pristine C60) in good yield.

PMID- 18327955
TI  - Synthesis of 2,4,5-trisubstituted 3-fluorofurans via sequential iodocyclization
      and cross-coupling of gem-difluorohomopropargyl alcohols.
AB  - The iodocyclization of gem-difluorohomoallenyl and gem-difluorohomopropargyl
      alcohols with I2 and ICl, respectively, produced the corresponding fluorinated
      iodofuran analogues in good yields. The iodo substituent in fluorinated 4
      iodofurans was utilized as a synthetic handle to prepare multi-substituted 3
      fluorofurans using a Suzuki cross-coupling reaction. The yields of both
      iodocyclization of gem-difluorohomopropargyl alcohol and subsequent Suzuki
      coupling were dramatically enhanced by microwave irradiation.

PMID- 18327956
TI  - Copper-nitrenoid formation and transfer in catalytic olefin aziridination
      utilizing chelating 2-pyridylsulfonyl moieties.
AB  - We have developed an efficient protocol for copper-catalyzed olefin aziridination
      using 5-methyl-2-pyridinesulfonamide or 2-pyridinesulfonyl azide as the nitrenoid
      source. The presence of a 2-pyridyl group significantly facilitates
      aziridination, suggesting that the reaction is driven by the favorable formation
      of a pyridyl-coordinated nitrenoid intermediate. Using this chelation-assisted
      strategy, synthetically acceptable yields of aziridines could be obtained with a
      range of aryl olefins even in the absence of external ligands. Importantly, a
      large excess of olefin is not required. X-ray crystallography, ESI-MS, Hammett
      plot analysis, kinetic studies, and computational undertakings strongly support
      that the observed aziridination is driven by internal coordination.

PMID- 18327957
TI  - Effect of temperature on self-assembly of bovine beta-casein above and below
      isoelectric pH. Structural analysis by cryogenic-transmission electron microscopy
      and small-angle X-ray scattering.
AB  - beta-Casein is one of the main proteins in milk, recently classified as an
      intrinsically unstructured protein. At neutral pH, it is composed of a highly
      polar N-terminus domain and a hydrophobic C-terminus tail. This amphiphilic block
      copolymer-like structure leads to self-organization of the protein monomers into
      defined micelles. Recently, it has been shown that at room temperature, beta
      casein also self-organizes into micelles in an acidic environment, but the effect
      of temperature on the micelles' formation and properties at the low pH regime
      were not explored. In the present study, we used two complementary techniques,
      cryogenic-transmission electron microscopy (cryo-TEM) and small-angle X-ray
      scattering (SAXS), to characterize at high-resolution the micelles' shape,
      dimensions, and aggregation numbers and to determine how these properties are
      affected by temperature between 1 and 40 degrees C. Two different regimes were
      studied: highly acidic pH where the protein is cationic, and neutral pH, where it
      is anionic. We found that flat disk-like micelles with low aggregation numbers
      formed at low temperature in the two pH regimes. Close to neutral pH increase in
      temperature involves a transition in the micelles' shape and dimensions from flat
      disks to bulky, almost spheroidal micelles, coupled with a sharp increase in the
      micelles' aggregation number. In contrast, no effects on the micelles' morphology
      or aggregation number were detected in the acidic environment within the entire
      temperature range studied. The self-organization into disk micelles and the lack
      of effect of temperature in the acidic environment are linked to the unstructured
      character of the protein and to the charge distribution map. The latter indicates
      that below the isoelectric pH (pI), beta-casein loses the distinct separation of
      hydrophobic and hydrophilic domains, thereby suggesting that it may no longer be
      considered as a classical head-tail block-copolymer amphiphile as in neutral pH.

PMID- 18327958
TI  - Interfacial self-organization of bolaamphiphiles bearing mesogenic groups:
      relationships between the molecular structures and their self-organized
      morphologies.
AB  - This article discusses the relationship between the molecular structure of
      bolaamphiphiles bearing mesogenic groups and their interfacial self-organized
      morphology. On the basis of the molecular structures of bolaamphiphiles, we
      designed and synthesized a series of molecules with different hydrophobic alkyl
      chain lengths, hydrophilic headgroups, mesogenic groups, and connectors between
      the alkyl chains and the mesogenic group. Through investigating their interfacial
      self-organization behavior, some experiential rules are summarized: (1) An
      appropriate alkyl chain length is necessary to form stable surface micelles; (2)
      different categories of headgroups have a great effect on the interfacial self
      organized morphology; (3) different types of mesogenic groups have little effect
      on the structure of the interfacial assembly when it is changed from biphenyl to
      azobenzene or stilbene; (4) the orientation of the ester linker between the
      mesogenic group and alkyl chain can greatly influence the interfacial self
      organization behavior. It is anticipated that this line of research may be
      helpful for the molecular engineering of bolaamphiphiles to form tailor-made
      morphologies.

PMID- 18327959
TI  - Friction dynamics of confined weakly adhering boundary layers.
AB  - The nanotribological behavior of self-assembled monolayers is investigated. The
      latter accommodate friction through transient relaxation and dilatancy effects
      whose kinetics depends on the structure of the confined layers. Thus, the
      molecular ordering onto the surfaces controls the level and the stability of the
      friction coefficient. Moreover, the behavior of these systems is theoretically
      accounted for using a model based on the kinetics of formation and rupture of
      adhesive bonds between the two shearing surfaces with an additional viscous term.

PMID- 18327960
TI  - Dynamics of spontaneous vesicle formation in fluorocarbon and hydrocarbon
      surfactant mixtures.
AB  - The spontaneous self-assembly of unilamellar vesicles was investigated by means
      of time-resolved synchrotron small-angle X-ray scattering. The self-assembly
      process was initiated by rapid mixing of anionic surfactant micelles with either
      zwitterionic or cationic surfactant micelles in equimolar ratio using a stopped
      flow device. For the zwitteranionic systems, transient disklike mixed micelles
      are observed as structural intermediates prior to the onset of vesiculation.
      These disklike micelles display an exponential growth law, and above a critical
      size they close to form unilamellar vesicles. In the catanionic system, the
      earliest observable structures within the mixing time of 4 ms are unilamellar
      vesicles. Nevertheless, in both systems a narrow distribution of the vesicle size
      was observed at the initial stages of their formation. The subsequent evolution
      of the vesicle size distribution depends on the subtle differences in the bilayer
      composition and properties.

PMID- 18327961
TI  - Continuous and size-dependent sorting of emulsion droplets using hydrodynamics in
      pinched microchannels.
AB  - In this report, a microfluidic system is presented for continuous and size
      dependent separation of droplets utilizing microscale hydrodynamics. The
      separation scheme is based on laminar-flow focusing and spreading in a pinched
      microchannel, referred to as "pinched flow fractionation (PFF)", which was
      previously developed for the size-dependent separation of solid particles, such
      as polymer microparticles or cells. By simply introducing emulsion and the
      continuous phase into a microchannel, continuous separation could be achieved
      without using complicated operations or devices. We first examined whether this
      scheme could be applied for droplets, by using a pinched microchannel with one
      outlet, and observed the behaviors of monodisperse droplets generated at the
      upstream T-junction. Analysis via high-speed imaging revealed that the length of
      the pinched segment is critical for precise separation of droplets. Then,
      separation of a polydisperse oil-in-water emulsion that was prepared previously
      was demonstrated using a microfluidic device equipped with multiple outlets.
      These results showed the ability of the presented system to sort or select
      specific-sized droplets easily and accurately, which would be difficult to
      achieve using normal-scale schemes, such as centrifugation or filtration.

PMID- 18327962
TI  - Polarization modulation infrared reflection absorption spectroscopy
      investigations of thin silica films deposited on gold. 2. Structural analysis of
      a 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer.
AB  - In this paper we report on the structural analysis of bilayers of 1,2-dimyristoyl
      sn-glycero-3-phosphocholine (DMPC) using polarization modulation infrared
      reflection absorption spectroscopy (PM IRRAS). The lipid bilayers were formed on
      SiO2|Au and Au surfaces using the Langmuir-Blodgett and Langmuir-Schaeffer
      techniques. As we showed in part 1 (Zawisza, I.; Wittstock, G.; Boukherroub, R.;
      Szunertis, S. Langmuir 2007, 23, 9303-9309), SiO2 layers of 7 nm thickness,
      synthesized by plasma-enhanced chemical vapor deposition on 200 nm thick gold
      covered glass slides, allow PM IRRAS investigations. Only minor changes in the
      order and structure of the lipid bilayer are observed when deposited on SiO2|Au
      and Au surfaces. The choline moiety in the leaflet directed toward the SiO2
      surface exists in trans conformation and shows a tilt of 28 degrees with the
      surface normal of the CN bond. On the silica surface in the second leaflet
      directed toward air and in two layers deposited on the Au surface, trans and
      gauche isomers of the choline moiety are present and the tilt of the CN bond
      increases to 55 degrees with respect to the surface normal. The order and
      molecular orientation in the DMPC bilayers on SiO2 and Au surfaces are not
      affected by time. The analysis of the phosphate stretching mode on the Au surface
      shows slight dehydration of this group and reorientation of the phosphate moiety.

PMID- 18327965
TI  - Mapping the integrin-linked kinase interactome using SILAC.
AB  - Protein-protein interactions play an essential role in the regulation of vital
      biological functions. Through a network of interactions, integrin-linked kinase
      (ILK) functions downstream of integrin receptors to control cell spreading,
      migration, growth, survival, and cell cycle progression. Despite many reports on
      the role of ILK in the regulation of multiple signaling pathways, it is still not
      understood how ILK integrates and controls complex cellular signals. A more
      global analysis of ILK-protein complexes will give important insights in the
      complexity of ILK-dependent signal transduction. Here, we applied a SILAC (stable
      isotope labeling with amino acids in cell culture)-based proteomics approach to
      discover novel ILK-interacting proteins. Of 752 proteins identified in ILK
      immunoprecipitates, 24 proteins had SILAC ratios higher than PINCH, previously
      identified as direct ILK-binding partner. Some of the newly identified proteins
      specifically enriched in ILK immunoprecipitates, with potentially interesting
      roles in ILK biology, include rapamycin-insensitive companion of mTOR (Rictor),
      alpha- and beta-tubulin, RuvB-like 1 and 2, HS1-associating protein 1 (HAX-1), T
      complex protein 1 subunits, and Ras-GTP-ase activating-like protein 1 (IQ-GAP1).
      Functional interactions between ILK and several of the new binding partners were
      confirmed by coimmunoprecipitation/Western blot and colocalization experiments.
      Detailed analysis showed that when ILK is found in a complex with alpha-tubulin
      and RuvB-like 1, alpha-parvin and PINCH are not present, suggesting that ILK has
      the ability to form distinct protein complexes throughout the cell. Inhibition of
      ILK activity with an ILK-kinase inhibitor QLT0267 or downregulation of its
      expression impaired the ability of RuvB-like 1 to bind to tubulin pointing toward
      a possible role of ILK in the regulation of RuvB-like 1/tubulin interaction.
      Using the power of quantitative proteomics to resolve specific from nonspecific
      protein interactions, we identified several novel ILK-binding proteins, which
      sheds light on the molecular mechanisms of regulation of ILK-dependent signal
      transduction.

PMID- 18327966
TI  - Reduction of fumonisin B1 in corn grits by single-screw extrusion.
AB  - This study was designed to determine the efficacy of extrusion in reducing
      fumonisin B1 in corn flaking grits in the presence and absence of glucose. In
      addition, degradation products of fumonisin B1 during extrusion were identified
      and quantitated with a mass balance approach. Uncontaminated clean corn grits,
      grits spiked with 30 microg/g fumonisin B1, and grits fermented with Fusarium
      verticillioides M-2552 (40-50 microg/g fumonisin B1) were extruded in the
      presence and absence of glucose (10%, w/w) using a single-screw extruder.
      Extrusion decreased fumonisin B1 by 21-37%, whereas the same process with added
      glucose further decreased fumonisin B1 by 77-87%. LC-fluorescence and LC-MS
      showed that most fumonisin in the extruded samples without added glucose was the
      fumonisin B1 form, whereas the main degradation product in grits extruded with
      glucose was N-(deoxy- d-fructos-1-yl)fumonisin B1. The formation of hydrolyzed
      fumonisin B1 was not significant during extrusion. Results suggest that extrusion
      in the presence of glucose may reduce fumonisin B1 in corn grits significantly.

PMID- 18327968
TI  - ADA's sedation and anesthesia guidelines pass: will they be universally accepted?

PMID- 18327969
TI  - Gow-Gates technique: a pilot study for extraction procedures with clinical
      evaluation and review.
AB  - The aim of this study was to compare the effectiveness of 2 different volumes of
      anesthetic solution for a premolar-molar extraction, and to determine the onset
      of complete mandibular conduction anesthesia via a Gow-Gates mandibular block.
      One operator performed 32 blocks with a 27-gauge needle on patients who required
      a dental extraction: 16 blocks using 1.8 mL of anesthetic solution, and 16 blocks
      using 3.6 mL of anesthetic solution. The parameters evaluated were frequency of
      successful anesthesia and onset of complete anesthesia. Significant differences
      (P < .005) were observed in the evaluation of volume: the 3.6 mL group yielded a
      higher success rate (82.5%) than the 1.8 mL group (17.5%). The onset of complete
      conduction anesthesia was achieved in 8 minutes by 56% of the subjects (9 of 16)
      with 3.6 mL and only one subject in 16 (6%) with 1.8 mL. A larger volume of
      anesthetic solution (3.6 mL) is required to achieve a higher success rate and a
      faster onset of action for a dental extraction without the use of reinforcement
      anesthesia. The volume of anesthetic solution is indirectly proportional to the
      onset of complete anesthesia. A premolar-molar extraction can be done, with 3.6
      mL of anesthetic solution, in more than 50% of the patients 8 minutes after
      injection.

PMID- 18327970
TI  - Heart rate effects of intraosseous injections using slow and fast rates of
      anesthetic solution deposition.
AB  - The authors, using a crossover design, randomly administered, in a single-blind
      manner, 3 primary intraosseous injections to 61 subjects using: the Wand local
      anesthetic system at a deposition rate of 45 seconds (fast injection); the Wand
      local anesthetic system at a deposition rate of 4 minutes and 45 seconds (slow
      injection); a conventional syringe injection at a deposition rate of 4 minutes
      and 45 seconds (slow injection), in 3 separate appointments spaced at least 3
      weeks apart. A pulse oximeter measured heart rate (pulse). The results
      demonstrated the mean maximum heart rate was statistically higher with the fast
      intraosseous injection (average 21 to 28 beats/min increase) than either of the 2
      slow intraosseous injections (average 10 to 12 beats/min increase). There was no
      statistically significant difference between the 2 slow injections. We concluded
      that an intraosseous injection of 1.4 mL of 2% lidocaine with 1 : 100,000
      epinephrine with the Wand at a 45-second rate of anesthetic deposition resulted
      in a significantly higher heart rate when compared with a 4-minute and 45-second
      anesthetic solution deposition using either the Wand or traditional syringe.

PMID- 18327972
TI  - Reactive oxygen and reactive nitrogen as signaling molecules for caspase 3
      activation in acute cardiac transplant rejection.
AB  - Apoptosis is a significant factor in cardiac dysfunction and graft failure in
      cardiac rejection. In this study, we examined potential signaling molecules
      responsible for caspase 3 activation in a model of acute cardiac allograft
      rejection. The roles of reactive oxygen species (ROS) and nitric oxide (NO) were
      determined in untreated allografts and allograft recipients treated with either
      cyclosporine (CsA), alpha-phenyl-t-butylnitrone (PBN, a spin-trapping agent),
      vitamin C (VitC), Mn(III)tetrakis (1-methyl-4-pyridyl)porphyrin); MnTmPyP, a
      superoxide dismutase (SOD) mimetic), or L-(1-iminoethyl)lysine) (L-NIL), an
      inhibitor of inducible NO synthase (iNOS) enzyme activity. Graft tissue was taken
      for measuring superoxide radical production, Western blotting, and direct
      measurement of caspase 3 activity. Activation of caspase 3 in untreated
      allografts was revealed by the appearance of cleaved caspase 3 from pro-caspase 3
      by Western blotting and functional caspase 3 catalytic activity. CsA or PBN
      inhibited iNOS expression and caspase 3 activity. VitC and MnTmPyP did not alter
      iNOS expression or decrease NO levels but did inhibit caspase 3 activity. In
      contrast, L-NIL completely inhibited the increase in NO production without
      altering iNOS expression and inhibited caspase 3 activity. The prevention of
      TUNEL staining by MnTmPyP and L-NIL confirmed downstream effects of superoxide
      and NO on apoptosis. These studies indicate that both superoxide and NO
      (precursors of peroxynitrite formation) play a significant role in caspase 3
      activation in cardiac allograft rejection.

PMID- 18327973
TI  - Elevated substance P levels in HIV-infected women in comparison to HIV-negative
      women.
AB  - Substance P and its receptor (neurokinin-1R) are potent modulators of
      neuroimmunoregulation and HIV/AIDS infection. We previously demonstrated that HIV
      seropositive men had significantly higher substance P levels compared to
      uninfected controls. We now demonstrate that substance P plasma levels are
      significantly higher in HIV-infected women in comparison to uninfected control
      women.

PMID- 18327971
TI  - Intracellular iron transport and storage: from molecular mechanisms to health
      implications.
AB  - Maintenance of proper "labile iron" levels is a critical component in preserving
      homeostasis. Iron is a vital element that is a constituent of a number of
      important macromolecules, including those involved in energy production,
      respiration, DNA synthesis, and metabolism; however, excess "labile iron" is
      potentially detrimental to the cell or organism or both because of its propensity
      to participate in oxidation-reduction reactions that generate harmful free
      radicals. Because of this dual nature, elaborate systems tightly control the
      concentration of available iron. Perturbation of normal physiologic iron
      concentrations may be both a cause and a consequence of cellular damage and
      disease states. This review highlights the molecular mechanisms responsible for
      regulation of iron absorption, transport, and storage through the roles of key
      regulatory proteins, including ferroportin, hepcidin, ferritin, and frataxin. In
      addition, we present an overview of the relation between iron regulation and
      oxidative stress and we discuss the role of functional iron overload in the
      pathogenesis of hemochromatosis, neurodegeneration, and inflammation.

PMID- 18327974
TI  - Analysis of putative N-linked glycosylation sites and variable region of envelope
      HIV-1 CRF07_BC recombinant in intravenous drug users in Xinjiang Autonomous
      Region, China.
AB  - To investigate more closely the determinants of transmission and escape in HIV-1
      internal proteins, we analyzed the characterization of putative N-linked
      glycosylation sites (PNGSs) and the variable loop of CRF07_BC recombinant human
      immunodeficiency virus type 1 (HIV-1), isolated from intravenous drug users
      (IDUs). We studied the characterization of PNGSs and the variable loop in the C1
      C5 and V1-V4 regions of the HIV-1 env gene in 12 intravenous drug users (IDUs)
      who were divided into two groups according to the length of infection time. In
      addition, two IDUs were longitudinally monitored from the time of seroconversion
      for 1.5 and 2.5 years. The longitudinal characterization within the individuals
      on PNGSs and the variable loop in the C1-C5 and V1-V4 region were also observed.
      Based on the above analysis, we found that PNGSs and the variable loop appeared
      to increase over time within IDU transmission of CRF07_BC recombinant HIV-1. We
      argue that limited PNGSs and the length of variable loops may be involved in
      selective transmission and escape.

PMID- 18327975
TI  - Enhancement of OX40-induced apoptosis by TNF coactivation in OX40-expressing T
      cell lines in vitro leading to decreased targets for HIV type 1 production.
AB  - OX40, a member of the tumor necrosis factor receptor (TNF-R) superfamily, has
      been shown to play an important role in the survival of antigen-specific CD4(+) T
      cells. We have previously reported that stimulation of the OX40-expressing and
      HIV-1 chronically infected T cell line, ACH-2/OX40, with either OX40 ligand
      (OX40L)-expressing cells or with TNF resulted in the activation of HIV-1 followed
      by apoptotic cell death. In the present study we found that costimulation via
      OX40 and TNF-R in OX40-expressing HIV-1-infected T cell lines leads to a marked
      reduction of HIV-1 production associated with rapid cell death. Since HIV-1
      negative OX40(+) T cell lines underwent rapid apoptotic cell death after OX40L
      and TNF stimulation, it was reasoned that the ACH-2/OX40 cell death was unlikely
      to be due to HIV-1 infection. Furthermore, we found that the OX40-mediated
      apoptosis of the CD4(+) T cell line, Molt-4/CCR5-OX40 (M/R5-OX40), required (1)
      signals mediated via the cytoplasmic tail of OX40, (2) activation of the caspase
      cascade, including caspase-8 and caspase-3, and (3) induction of endogenous TNF
      alpha, but not of TNF-beta, FasL, or TNF-related apoptosis-inducing ligand
      (TRAIL), suggesting that this apoptosis occurred indirectly via the TNF/TNF-R
      system. Finally, a fraction of primary activated CD4(+) T cells, expressing high
      levels of OX40, underwent apoptosis, as revealed by annexin V staining, after
      cocultivation with OX40L(+) cells. These results suggest a new biological role of
      the OX40L/OX40 system in controlling the fate of activated CD4(+) T cells and of
      controlling HIV-1 infection in inflammatory environments.

PMID- 18327976
TI  - Tolerability and effectiveness of first-line regimens combining nevirapine and
      lamivudine plus zidovudine or stavudine in Cameroon.
AB  - We compared the tolerability and effectiveness of two major first-line regimens
      used in resource-limited settings, namely zidovudine-lamivudine-nevirapine and
      stavudine-lamivudine-nevirapine. HIV-1-infected adults in Cameroon were enrolled
      in a prospective cohort study between 2001 and 2003. They were eligible if they
      had AIDS or a CD4 cell count below 350/mm(3), a Karnofsky score over 50%, and no
      contraindications to antiretroviral treatment. The patients were followed up to 2
      years. Of 169 patients, 85 received zidovudine-lamivudine-nevirapine and 84
      stavudine-lamivudine-nevirapine. The incidence rates of treatment changes, death,
      drug resistance, and severe adverse effects were, respectively, 12.0 [95%
      confidence interval (CI) 7.2-19.9] and 10.9 (CI 6.4-18.3) per 100 person-years;
      5.7 (CI 2.8-11.4) and 7.6 (CI 4.2-13.7); 2.9 (CI 1.1-7.7) and 5.0 (CI 2.4-10.6);
      and 41.7 (CI 30.2-57.6) and 49.1 (CI 36.1-66.6). The Kaplan-Meier curves for the
      likelihood of remaining on the initial regimen (p = 0.8) and for survival (p =
      0.5) did not differ significantly between the groups. In Cox multivariate
      analysis only a lower baseline CD4 cell count was associated with death (p <
      0.001). The proportion of patients with undetectable viral load and the increase
      in the CD4 cell count were similar in the two groups. Anemia was rare (4% vs.
      6%). Five cases of severe peripheral neuropathy and one case of lipodystrophy
      occurred. This study suggests that the zidovudine-lamivudine-nevirapine
      combination is a safe first-line treatment, even in settings with few laboratory
      resources. In view of stavudine toxicity, these results support recommendations
      calling for a gradual switch from stavudine- to zidovudine-based regimens.

PMID- 18327977
TI  - Planned multiple exposures to autologous virus in HIV type 1-infected pediatric
      populations increases HIV-specific immunity and reduces HIV viremia.
AB  - We tested to determine if planned multiple exposures to autologous HIV in
      pediatric patients with HIV-1 infection will induce cellular immunity that
      controls viremia. A prospective multicenter study of aviremic pediatric patients
      on highly active antiretroviral therapy who underwent progressively longer
      antiretroviral treatment interruptions in cycles starting with 3 days, increasing
      by 2 days in length each consecutive cycle, was conducted. Eight individuals
      became viremic and reached Cycle 13 or greater with an "off-therapy" interval of
      >or=27 days. HIV-specific interferon-gamma (IFN-gamma) production to inactivated
      HIV and vaccinia vectors expressing gag, env, nef, and pol increased (>10-fold)
      from baseline in six of eight subjects. The HIV-specific lymphoproliferative
      response as measured by the median stimulation index (SI) increased in the
      treatment group from 1 at baseline to 16, 12, 4, and 3 at Cycles 7, 10, 13, and
      17, respectively. Median plasma RNA levels peaked at Cycle 7 (4.45 log) and
      declined to levels <10(4) cp/ml after Cycle 10 (4.1, 3.5, and 3.4 at Cycles 10,
      13, and 17). In a subset of five patients who reached Cycle 17, HIV-specific IFN
      gamma frequencies were 4- to 30-fold higher and median RNA levels were 0.32-2.10
      (median 1.3) log lower than at comparable days off treatment at Cycle 8 (17 days
      off therapy). A second group of children, not undergoing drug interruption, did
      not develop significant increases in either HIV-specific IFN-gamma production or
      SI. Increased HIV-specific immune responses and decreased HIV RNA were seen in
      those children who have had >10 cycles of antiretroviral discontinuations of
      increasing durations acting as autologous virus vaccinations. Other studies may
      have failed due to an insufficient number of exposures to HIV; most of the
      studies had fewer than six drug interruptions.

PMID- 18327978
TI  - CCR5-restricted HIV type 2 variants from long-term aviremic individuals are less
      sensitive to inhibition by beta-chemokines than low pathogenic HIV type 1
      variants.
AB  - Many HIV-2-infected individuals maintain low, often undetectable, viral loads for
      prolonged periods. Virus and/or host factors that contribute to this high level
      of virus control are largely unknown. Previously we demonstrated that HIV-2
      variants from long-term aviremic individuals have relatively low replication
      kinetics in vitro in comparison to HIV-1 variants. We hypothesized that the
      relatively low replication rates of HIV-2 in vitro as well as the high level of
      virus control in vivo might be explained by HIV-2 replication being more
      sensitive to inhibitory host factors like beta-chemokines or other CD8+ T cell
      derived factors than HIV-1 replication. To test this we determined the effect of
      exogenously added beta-chemokines and healthy donor CD8+ T cells on the in vitro
      virus production of HIV-2 and HIV-1 variants from long-term nonprogressors
      (LTNPs). Contrary to expectations, HIV-2 replication was inhibited less
      efficiently by RANTES and MIP-1alpha than HIV-1 replication. CD8+ T cells from 8
      of 12 healthy donors reduced HIV replication minimally 2-fold. Interestingly,
      cells from five of these donors inhibited HIV-1 but hardly affected HIV-2
      replication, while the reverse was observed for cells from one donor. For HIV-1,
      but not HIV-2, the magnitude of the antiviral effect of CD8+ T cells correlated
      with their effect on RANTES levels in culture supernatants. Our findings indicate
      that RANTES is a more important factor of CD8+ T cell-associated anti-HIV-1
      activity than it is of HIV-2 activity and that the benign clinical course of HIV
      2 infection is not due to enhanced beta-chemokine sensitivity of HIV-2 variants.

PMID- 18327979
TI  - Effects of low HIV type 1 load and antiretroviral treatment on IgG-capture BED
      enzyme immunoassay.
AB  - The IgG-capture BED-enzyme immunoassay (BED-CEIA) is used widely at present to
      detect recent HIV-1 seroconversion. However, antibody levels and antibody
      kinetics are impacted by HIV-1 load and antiretroviral treatment, which may have
      a significant effect on the assay results. In this study, we analyzed serial
      samples from 11 patients with recent infection, including four patients treated
      by structured treatment interruption (STI), and compared the results with those
      of 10 untreated and 7 treated patients with chronic infection. The BED-CEIA
      missidentified one long-term nonprogressor hemophiliac with an extremely low HIV
      1 load and five patients with chronic infection who received antiretroviral
      treatment. We also found that the ODn values increased slowly in patients with
      recent infection and low HIV-1 loads and that the ODn values fluctuated in
      parallel with HIV-1 load during STI. Our data indicate that the results of BED
      CEIA are influenced by HIV-1 load and antiretroviral treatment. Care should be
      taken when interpreting the results of BED-CEIA, especially in individuals with
      low HIV-1 loads. Those on antiretroviral treatment should be excluded from BED
      CEIA testing to improve the predictive value of detecting recent infections.

PMID- 18327980
TI  - R5 and X4 HIV viruses differentially modulate host gene expression in resting
      CD4+ T cells.
AB  - During HIV-1 infection, distinct biological phenotypes are observed between R5
      and X4 HIV-1 strains with respect to pathogenicity and tropism. In this study,
      temporal changes of the expression levels of the complete human transcriptome,
      representing 47,000 well-characterized human transcripts, were monitored in the
      first 24 h during HIV-1 R5 and X4 exposition in resting primary CD4(+) T cells.
      We provide evidence that R5 viruses modulate, to a greater extent than X4
      viruses, the level of mRNA of the resting CD4(+) T cells. Indeed, modulation of
      the TCR signaling and the actin organization involving the WAVE/ABI complex and
      the ARP2/3 complex appeared to be associated with R5 exposition. The data suggest
      that the ability of R5 viruses to modulate TCR-mediated actin polymerization and
      signaling creates a favorable environment for CD4(+) T cell activation after TCR
      stimulation and may partly explain why R5 is the primary strain observed early in
      the natural infection process.

PMID- 18327981
TI  - Emergence of an NNRTI resistance mutation Y181C in an HIV-infected NNRTI-naive
      patient.
AB  - The purpose of our study was to examine the emergence of the Y181C resistance
      mutation in an NNRTI-naive subject (index patient) at different time points.
      Phylogenetic trees in protease (PR) and partial reverse transcriptase (RT)
      regions were inferred by the maximum likelihood (ML) method. The Y181C mutation
      was detected for the first time when the patient was receiving d4T + ddI + LPV/r;
      the previous drug combination was 3TC + AZT + IDV. The particular mutation
      (Y181C) was not present at any time point during the treatment period with 3TC +
      AZT + IDV. Moreover, there was no evidence of resistance mutations in RT before
      the initiation of antiretroviral therapy. Phylogenetic analysis including
      sequences from the index patient and his spouse sampled at different time points,
      as well as control sequences belonging to the same HIV-1 subtype, revealed that
      there is no evidence of coinfection or reinfection with Y181C resistance strains,
      while the virus for both subjects was classified as subtype CRF14_BG. Overall,
      our findings suggest that the Y181C resistance mutation may be selected, not only
      by NNRTIs, but also by d4T. This may be of particular significance in developing
      countries where treatment with Triomune, a fixed combination of d4T, ddI, and
      nevirapine, is common. The genetic barrier against resistance of this combination
      may be lower than previously thought.

PMID- 18327982
TI  - HERV-K113 is not associated with multiple sclerosis in a large family-based
      study.
AB  - Numerous studies have invoked a role for retroviruses in multiple sclerosis (MS).
      Most have identified human endogenous retroviruses (HERVs) as possible
      etiological agents. The majority of HERVs originate from ancestral infection and
      then become progressively disabled by mutations over millions of years of primate
      evolution. Their presence in 100% of healthy humans, together with the paucity of
      functional retroviral genes, argues strongly against a causal role in disease.
      Recently, a new class of insertionally polymorphic HERVs has been described that
      is present in only a proportion of the population. One of them, HERV-K113, is
      notable for open reading frames for all of its genes and is found in 0-28% of
      humans with widespread geographic and racial variation. Thus HERV-K113 is a
      credible candidate for causing disease in a manner comparable to infectious
      retroviruses. Genomic DNA samples from 951 patients with MS were tested for the
      presence of the HERV-K113 allele by PCR, with their unaffected parents (n = 1902)
      acting as controls. HERV-K113 provirus was found in 70 out of 951 (7.36%)
      patients with MS and was not significantly increased compared to the combined
      parent group (6.52%). The results do not support an association between this
      endogenous retrovirus and MS. This study also emphasizes the need for large
      cohorts with controls for race and geographic location when examining possible
      links between polymorphic HERVs and disease.

PMID- 18327984
TI  - Identification of a strongly activating human anti-CD40 antibody that suppresses
      HIV type 1 infection.
AB  - We characterized the functional properties of a novel set of human anti-CD40
      monoclonal antibodies originating from a human phage display library and
      identified an antibody that strongly activates cells via the CD40 receptor for
      potential use in HIV therapy. The anti-CD40 antibodies were converted from a
      single chain antibody fragment format (scFv) to an IgG format and produced in
      HEK293 cells, and the binding characteristics were evaluated. Next, their ability
      to (1) rescue a human B cell line from induced apoptosis, (2) stimulate B cell
      proliferation, and (3) block the CD40-CD40L interaction was determined. Finally,
      the most activating anti-CD40 antibody was tested for its ability to block HIV-1
      infection in a monocyte-derived cell line. The different anti-CD40 antibodies,
      A24, B44, E30, F33, and A2-54, displayed a wide variety of binding and functional
      properties. In particular, B44 showed a very strong ability to activate normal
      human B cells and, in addition, did not block the CD40-CD40L interaction. This
      antibody was able to suppress HIV-1 infection in a human cell line (MonoMac 1)
      and may be a potential therapeutic candidate in HIV infection.

PMID- 18327985
TI  - Upregulation of human cytomegalovirus by HIV type 1 in human lymphoid tissue ex
      vivo.
AB  - HIV-1 copathogens are believed to play a critical role in progression to AIDS.
      Human cytomegalovirus (HCMV) has a high prevalence in the general population and
      is a common copathogen in HIV-1-infected individuals. Important events in
      copathogen interactions with HIV-1 take place in lymphoid tissue where critical
      events in HIV-1 disease occur. Here, we used an experimental system of human
      lymphoid tissue ex vivo to investigate interactions of HCMV with HIV-1. We
      inoculated ex vivo blocks of human lymphoid tissue with a recombinant strain of
      HCMV, expressing the green fluorescent protein, and HIV-1 and monitored viral
      replication and the phenotype of productively infected cells. HCMV readily
      replicated in tissue blocks as revealed by the release of HCMV viral DNA and an
      increasing number of viral-positive cells. Immunophenotyping of HCMV-infected
      cells showed a preferential infection of activated lymphocytes. The number of
      these cells significantly increased in HIV-1-coinfected tissues. Accordingly,
      HCMV replication was enhanced 2- to-3 fold. This upregulation occurred in tissues
      infected with either CXCR4- or CCR5-utilizing HIV-1. Thus, HIV-1 creates new
      targets for HCMV, which may explain the strong association of HCMV with HIV-1
      infection in vivo. Ex vivo-infected human lymphoid tissue constitutes a model to
      study the mechanisms of HCMV tissue pathogenesis and its interactions with HIV-1
      and this model may provide new targets for anti-HIV-1 therapy.

PMID- 18327986
TI  - Resistance profile of darunavir: combined 24-week results from the POWER trials.
AB  - The resistance profile of darunavir (TMC114) in treatment-experienced patients
      was explored using pooled week 24 data from POWER 1, 2, and 3 at the recommended
      dose of darunavir with low-dose ritonavir (darunavir/r, 600/100 mg bid, N = 458).
      Baseline darunavir fold change in EC(50) was a strong predictor of virological
      response at week 24. Preliminary phenotypic clinical cut-offs of 10 and 40 were
      established. Virological response to darunavir/r was maintained in the presence
      at baseline of a high number of IAS-USA PI resistance-associated mutations (IAS
      USA PI RAMS); a diminished response occurred with >or=14. Eleven protease
      mutations associated with diminished darunavir/r virological response were
      identified (V11I, V32I, L33F, I47V, I50V, I54L/M, G73S, L76V, I84V, and L89V).
      These darunavir resistance-associated mutations (DRV RAMS) occurred in the
      presence of a high number of IAS-USA PI RAMS. Virological response was diminished
      with three or more DRV RAMS in the background of a high number of IAS-USA PI
      RAMS. Incremental numbers of DRV RAMS were more predictive of outcome than were
      IAS-USA PI RAMS. Mutations developing during darunavir/r virological failure
      (V32I, L33F, I47V, I54L, and L89V) were also featured in the DRV RAMS list. Site
      directed mutants carrying these five mutations, or any one of these mutations
      either alone or together with one or two IAS-USA PI RAMS, showed no reduced
      darunavir susceptibility, suggesting that a high number of additional background
      mutations is required for darunavir resistance. In this population of treatment
      experienced patients, darunavir/r demonstrated significantly greater efficacy
      than investigator-selected control PIs of trials POWER 1 and 2, regardless of
      baseline viral genotype or phenotype, while exhibiting a high genetic barrier to
      the development of resistance.

PMID- 18327983
TI  - Prevalence and epidemiology of HIV type 1 drug resistance among newly diagnosed
      therapy-naive patients in Belgium from 2003 to 2006.
AB  - This study is the first prospective study to assess the prevalence, epidemiology,
      and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected
      patients in Belgium. In January 2003 it was initiated as part of the pan-European
      SPREAD program, and continued thereafter for four inclusion rounds until December
      2006. Epidemiological, clinical, and behavioral data were collected using a
      standardized questionnaire and genotypic resistance testing was done on a sample
      taken within 6 months of diagnosis. Two hundred and eighty-five patients were
      included. The overall prevalence of transmitted HIV-1 drug resistance in Belgium
      was 9.5% (27/285, 95% CI: 6.6-13.4). Being infected in Belgium, which largely
      coincided with harboring a subtype B virus, was found to be significantly
      associated with transmission of drug resistance. The relatively high rate of
      baseline resistance might jeopardize the success of first line treatment as more
      than 1 out of 10 (30/285, 10.5%) viruses did not score as fully susceptible to
      one of the recommended first-line regimens, i.e., zidovudine, lamivudine, and
      efavirenz. Our results support the implementation of genotypic resistance testing
      as a standard of care in all treatment-naive patients in Belgium.

PMID- 18327987
TI  - Genetic characterization of HIV type 1 long terminal repeat following vertical
      transmission.
AB  - Human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) sequences
      were characterized from six mother-infant pairs following vertical transmission.
      The LTR sequences exhibited a low degree of heterogeneity within mothers, within
      infants, and between epidemiologically linked mother-infant pairs. However, LTR
      sequences were more heterogeneous between epidemiologically unlinked individuals
      compared with linked mother-infant pairs. These data were further supported by
      low estimates of genetic diversity and clustering of each mother-infant pair's
      sequences into a separate subtree as well as the presence of common signature
      sequences between mother-infant pairs. The functional domains essential for LTR
      (promoter) function, including the promoter (TATAA), enhancers (three Sp-I and
      two NF-kappaB), the modulatory regions (two AP-I sites, two NFAT, one NF-IL6
      site, one Ets-1, and one USF-1), and the TAR region were generally conserved
      among mother-infant pairs. Taken together, limited heterogeneity and conservation
      of functional domains in the LTR following vertical transmission support the
      notion that a functional LTR is critical in viral replication and pathogenesis in
      HIV-1-infected mothers and their infected infants.

PMID- 18327988
TI  - HIV type 1 pol gene diversity and antiretroviral drug resistance mutations in
      Santos, Brazil.
AB  - HIV-1 antiretroviral drug resistance mutations in subtype B, F, and recombinants
      B/F in Santos, Brazil were characterized. We studied 83 samples from individuals
      enrolled at the Brazilian HIV/AIDS programs from Santos. These patients have been
      treated with multiantiretroviral therapy. Samples were collected in 2006; RNA was
      extracted from plasma and used as a target to amplify the pol gene of HIV-1. PCR
      products were sequenced on both strands, phylogenetic analyses were performed by
      neighbor-joining, and recombination was evaluated by bootscan. pol gene
      sequencing of the samples revealed that 54 strains belonged to subtype B, 4 were
      subtype F, 1 was subtype C, and 24 were B/F recombinants. Recombinant break
      points in 20 samples are the same identified in CRF28_BF and CRF29_BF. Drug
      resistance mutations identified in common to subtypes B, F, and recombinants B/F
      were protease inhibitors M46I/L (29%), I54V (24%), A71V (22%), and V82A/F (31%);
      reverse transcriptase nucleoside resistance mutations M41L (52%), D67N (30%),
      K70R (26%), M184V (88%), L210W (29%), T215Y/I/F (65%), and K219Q/E/N (28%); and
      reverse transcriptase nonnucleoside resistance mutation K103N (52%). Our results
      suggest that, in general, the same amino acids are emerging in both subtypes B,
      F, and recombinant forms BF due to the selective pressure of antiretrovirals.
      Recombinant break points in samples are the same as identified in CRF28_BF and
      CRF29_BF and are recognized as important for the evolution of the local epidemic.

PMID- 18327989
TI  - Diabetic stress: new triumphs and challenges to maintain vascular longevity.

PMID- 18327991
TI  - Treatment of hypertension in individuals with the cardiometabolic syndrome: role
      of an angiotensin II receptor blocker, telmisartan.
AB  - Arterial hypertension is a global public health problem owing to its high
      prevalence and association with increased risk for cerebral, cardiac and renal
      events. Hypertension frequently clusters with other cardiometabolic risk factors,
      such as dysglycemia, low levels of high-density lipoprotein cholesterol and high
      triglyceride levels. These, along with other factors such as central obesity,
      increased inflammation, endothelial dysfunction and thrombosis, are components of
      the metabolic syndrome. All guidelines recommend that the first-line therapy in
      metabolic syndrome should be based on lifestyle modification, consisting of diet
      and moderate exercise for at least 30 min/day. Concerning drug treatment of
      hypertension associated with other cardiometabolic risk factors, many results of
      head-to-head studies have demonstrated a reduction in new-onset Type 2 diabetes
      in hypertensive patients treated with angiotensin-converting enzyme inhibitors
      and angiotensin receptor blockers, when compared with conventional
      antihypertensive therapy. The explanations of the different actions of both these
      drugs include several mechanisms related to pancreatic insulin release and
      insulin sensitivity improvement. Another mechanism by which the inhibition of the
      renin-angiotensin system may improve insulin sensitivity is through the partial
      peroxisome proliferator-activated receptor-gamma agonism of telmisartan. For that
      reason, telmisartan has been considered by some experts to be an antihypertensive
      agent that is particularly useful in the treatment of hypertension associated
      with cardiometabolic risk factors. The impact of the promising metabolic action
      exhibited by telmisartan on the outcome of hypertensive patients aggregating
      other cardiometabolic risk factors waits for adequately randomized and powered
      clinical trials.

PMID- 18327992
TI  - Aliskiren-hydrochlorothiazide combination for the treatment of hypertension.
AB  - Hypertension is a major risk factor for cardiovascular morbidity and mortality
      and currently has been estimated at 30% of the US population. Of these, only
      36.8% have their blood pressure reduced to recommended levels of lower than
      140/90 mmHg for uncomplicated hypertension, or less than 130/80 mmHg for patients
      with diabetes mellitus or renal disease. Since monotherapy controls blood
      pressure in less than 50% of treated hypertensive patients, combination therapy
      is often required to bring blood pressure to the recommended levels of the 7th
      Joint National Committee report. One of the most effective and widely used
      combinations is the combination of an angiotensin-converting enzyme inhibitor or
      angiotensin receptor blocker with hydrochlorothiazide (HCTZ). Aliskiren, a new
      blocker of the renin-angiotensin system has been developed and approved by the US
      FDA on 18th January 2008 for the treatment of hypertension. Aliskiren is a direct
      inhibitor of renin, the rate-limiting enzyme for the production of angiotensin
      II, a powerful vasoconstrictive peptide. Several randomized clinical trials have
      demonstrated that aliskiren administered in single daily doses of 150, 300 or 600
      mg alone and in combination with HCTZ 12.5 and 25 mg is effective in lowering
      blood pressure, and is safe and well tolerated. In this article, the
      pharmacokinetic and pharmacodynamic profile and the clinical application of
      aliskiren alone and in combination with HCTZ will be discussed.

PMID- 18327993
TI  - Early-onset Type 2 diabetes mellitus: an increasing phenomenon of elevated
      cardiovascular risk.
AB  - The age of onset of Type 2 diabetes mellitus (T2DM) is falling and this condition
      is not uncommon among those aged less than 30 years, including children and
      adolescents. Early-onset T2DM has been reported in countries with different
      ethnic and cultural backgrounds. This phenomenon heralds an important public
      health issue reflecting the effects of a sedentary lifestyle as part of the
      globalization and industrialization that is affecting all societies. The
      pathophysiology of early-onset T2DM is similar to the later onset cohort
      characterized by beta-cell failure and obesity-induced insulin resistance but the
      rate of decline in beta-cell function appears to be more rapid. Recent evidence
      suggests that early-onset T2DM is a more aggressive disease phenotype than the
      later onset cohort and develops cardiovascular complications, reflected by more
      adverse cardiovascular risk profile and higher relative risk of myocardial
      infarction and cardiovascular death. As there is a paucity of clinical trial
      evidence in this population, clinical judgment is required to initiate treatments
      to prevent cardiovascular complications guided by assessment of global
      cardiovascular risk. Future research strategies in this cohort include population
      based studies in at-risk populations, exploration of its natural history,
      development of complications and outcome studies pertaining to the treatment of
      cardiovascular risk factors.

PMID- 18327994
TI  - Type 2 diabetes mellitus: prevention of macrovascular complications.
AB  - Type 2 diabetes mellitus is a disease that affects a rapidly increasing number of
      patients. Most patients with Type 2 diabetes will develop vascular complications.
      This may be microvascular disease, such as nephropathy, retinopathy or
      polyneuropathy, and also macrovascular disease, such as coronary heart disease,
      stroke or peripheral artery disease. Optimal control of elevated blood glucose
      levels will reduce the symptoms of hyperglycemia and help to prevent the
      development of complications. In addition, treatment of hypertension and lipid
      disturbances has been shown to reduce the incidence and severity of vascular
      complications significantly. The current treatment goals focus on adequate and
      aggressive treatment of these three risk factors. The central dogma for treatment
      of blood glucose, blood pressure and cholesterol levels is 'the lower the
      better'. Ongoing trials evaluate the effect of further lowering these treatment
      goals and of specific types of medication on cardiovascular events.

PMID- 18327995
TI  - Pathogenic potential of adipose tissue and metabolic consequences of adipocyte
      hypertrophy and increased visceral adiposity.
AB  - When caloric intake exceeds caloric expenditure, the positive caloric balance and
      storage of energy in adipose tissue often causes adipocyte hypertrophy and
      visceral adipose tissue accumulation. These pathogenic anatomic abnormalities may
      incite metabolic and immune responses that promote Type 2 diabetes mellitus,
      hypertension and dyslipidemia. These are the most common metabolic diseases
      managed by clinicians and are all major cardiovascular disease risk factors.
      'Disease' is traditionally characterized as anatomic and physiologic
      abnormalities of an organ or organ system that contributes to adverse health
      consequences. Using this definition, pathogenic adipose tissue is no less a
      disease than diseases of other body organs. This review describes the
      consequences of pathogenic fat cell hypertrophy and visceral adiposity,
      emphasizing the mechanistic contributions of genetic and environmental
      predispositions, adipogenesis, fat storage, free fatty acid metabolism, adipocyte
      factors and inflammation. Appreciating the full pathogenic potential of adipose
      tissue requires an integrated perspective, recognizing the importance of 'cross
      talk' and interactions between adipose tissue and other body systems. Thus, the
      adverse metabolic consequences that accompany fat cell hypertrophy and visceral
      adiposity are best viewed as a pathologic partnership between the pathogenic
      potential adipose tissue and the inherited or acquired limitations and/or
      impairments of other body organs. A better understanding of the physiological and
      pathological interplay of pathogenic adipose tissue with other organs and organ
      systems may assist in developing better strategies in treating metabolic disease
      and reducing cardiovascular disease risk.

PMID- 18327996
TI  - Advances in the management of hyperlipidemia-induced atherosclerosis.
AB  - Although hyperlipidemia clearly plays a role in developing cardiovascular
      disease, the 10% of the population with the highest LDL levels account for only
      20% of cardiovascular disease events. Thus, in order to significantly reduce the
      burden of cardiovascular disease, subjects with only modest dyslipidemia need to
      be treated with lipid-lowering therapy. Current guidelines have recommended
      aggressive lipid-lowering therapy in subjects at high risk of cardiovascular
      disease. The rationale behind this and treatment options to achieve target lipid
      goals are discussed.

PMID- 18327997
TI  - Aortic sclerosis, aortic stenosis and lipid-lowering therapy.
AB  - Calcific aortic stenosis (AS) is a progressive disease that has, until recently,
      been considered to be a degenerative and unmodifiable process induced by long
      lasting mechanical stress. However, histopathologic studies have now demonstrated
      that the development and progression of calcific AS is based on an active
      process, sharing a number of similarities with atherosclerosis. Inflammation,
      lipid infiltration, dystrophic calcification, ossification, platelet deposition
      and endothelial dysfunction have been observed in both diseases. In addition,
      several studies have suggested that AS and atherosclerosis share a number of risk
      factors, such as hypercholesterolemia, elevated lipoprotein (a), smoking,
      hypertension and diabetes. These findings suggest that statin therapy could be
      beneficial in AS by its lipid-lowering and/or anti-inflammatory effects, as is
      the case in atherosclerosis. Although this concept has been supported by
      experimental work and by four retrospective clinical studies observing
      significantly slower rates of hemodynamic progression in statin-treated patients,
      a prospective randomized trial (Scottish Aortic Stenosis and Lipid Lowering
      Trial, Impact on Regression [SALTIRE]; 80mg of atorvastatin vs placebo) yielded a
      negative result. In contrast to the retrospective analyses, according to the
      study protocol, patients with hyperlipidemia had to be excluded in this trial. A
      recent prospective study (Rosuvastatin Affecting Aortic Valve Endothelium
      [RAAVE]) treating hypercholesteremic patients with rosuvastatin, found a
      significantly slower rate of progression in these patients compared with patients
      with normal cholesterol levels who were left untreated, suggesting that statin
      therapy may only be beneficial in patients with hyperlipidemia. Lipid-lowering
      therapy with statins can, therefore, currently only be recommended in this
      subgroup of patients with AS.

PMID- 18327998
TI  - Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms
      of action and clinical implications.
AB  - Hypertriglyceridemia is a risk factor for atherosclerotic coronary heart disease.
      Very high triglyceride (TG) levels (> or =500 mg/dl [5.65 mmol/l]) increase the
      risk of pancreatitis. One therapeutic option to lower TG levels is omega-3 fatty
      acids, which are derived from the oil of fish and other seafood. The American
      Heart Association has acknowledged that fish oils may decrease dysrhythmias,
      decrease sudden death, decrease the rate of atherosclerosis and slightly lower
      blood pressure, and has recommended fish consumption or fish oil supplementation
      as a therapeutic strategy to reduce cardiovascular disease. A prescription omega
      3-acid ethyl esters (P-OM3) preparation has been available in many European
      nations for at least a decade, and was approved by the US FDA in 2004 to reduce
      very high TG levels (> or =500 mg/dl [5.65 mmol/l]). Mechanistically, most
      evidence suggests that omega-3 fatty acids reduce the synthesis and secretion of
      very-low-density lipoprotein (VLDL) particles, and increase TG removal from VLDL
      and chylomicron particles through the upregulation of enzymes, such as
      lipoprotein lipase. Omega-3 fatty acids differ mechanistically from other lipid
      altering drugs, which helps to explain why therapies such as P-OM3 have
      complementary mechanisms of action and, thus, complementary lipid benefits when
      administered with statins. Additional human studies are needed to define more
      clearly the cellular and molecular basis for the TG-lowering effects of omega-3
      fatty acids and their favorable cardiovascular effects, particularly in patients
      with hypertriglyceridemia.

PMID- 18327999
TI  - Venous thrombosis in children.
AB  - The advances in pediatric tertiary care have resulted in a decrease in the
      mortality of children with serious underlying conditions. Consequently, there has
      been an increase in previously rare complications of therapy in children,
      including venous thrombosis. Although there is a paucity of properly designed
      trials in the field of pediatric thrombosis, many advances have been made over
      the past 15 years. Venous thrombosis in children has been the subject of many
      reviews. This review is an update of the available evidence in the management of
      venous thrombosis in children, excluding thrombosis of the CNS.

PMID- 18328000
TI  - Arterial thrombosis in children.
AB  - Arterial thromboembolism is rare in children. The frequency of arterial
      thromboembolisms has paralleled the advances in pediatric tertiary care with
      increasing numbers of children surviving life-threatening primary illnesses and,
      paradoxically, developing previously rare complications. The pathophysiology of
      thrombosis in children differs from that of adults, underscoring the need for a
      unique diagnostic and therapeutic approach in pediatrics. This review is a
      summary of the available data on the etiology, diagnosis and management of
      arterial thrombosis, occurring outside of the CNS, in children.

PMID- 18328001
TI  - Class 1 integrons and Salmonella genomic island 1 among Salmonella enterica
      isolated from poultry and swine.
AB  - Two hundred eleven Salmonella enterica strains representing 35 serotypes isolated
      from healthy poultry (n=103) and swine (n=108) were used in this study. The
      occurrence and characteristics of class 1 integrons were investigated. Salmonella
      genomic islands (SGIs) and the horizontal transfer of integrons were assessed.
      One hundred eighty-six isolates (88%) were resistant to at least one
      antimicrobial and 140 isolates (66%) were multidrug resistant. The intI1 gene was
      present in 54 isolates (25.6%), of which 33 (15.6%) carried gene cassettes with
      sizes ranging from 0.7 to 2.3 kb. Sequence analysis revealed 11 distinct integron
      profiles in which resistance genes bla(PSE-1), dfrA1, dfrA12, aadA2, aadA4a, and
      silB were present. The gene cassette array dfrA12-aadA2 was the most prevalent
      among the isolates whereas most integrons were located on conjugative plasmids.
      SGI1 variants (SGI1-A and -F) were present in nine isolates belonging to serovars
      Albany, Emek, Kedougou, and Kingston.

PMID- 18328002
TI  - Making the political case for biogerontology funding: a view from the trenches.

PMID- 18328003
TI  - Selective decline of the metabolic competence of oversized synaptic mitochondria
      in the old monkey cerebellum.
AB  - The morphofunctional features of synaptic mitochondria, positive to the activity
      of cytochrome oxidase (COX), were investigated in the cerebellar cortex of adult
      and old monkeys (Macaca fascicularis) to assess the potential age-related changes
      in the energy metabolism occurring at the neuronal synaptic compartment. The
      following mitochondrial ultrastructural parameters-numeric density (Nv), volume
      density (Vv), average volume (V), and average length (Fmax)-were measured by
      computer-assisted morphometric methods. The ratio (R) area of the COX
      cytochemical precipitate/area of the mitochondrion was semi-automatically
      calculated and considered as an estimation of the mitochondrial metabolic
      competence (MMC), that is, the capacity of single organelles to provide adequate
      amounts of adenosinetriphosphate. No age-related significant differences were
      found in any of the ultrastructural parameters taken into account, whereas a
      significant decrease of R was observed in old animals. In these animals, the
      quartile distribution of the COX-positive organelles, according to their
      respective cross-sectional area, showed no significant difference of R when
      comparing small (I quartile), medium-sized (II quartile), and large (III
      quartile) mitochondria, while a significant decrease of R was evident in
      oversized mitochondria (IV quartile). Although our data document an age-related
      preservation of the morphological features of COX-positive mitochondria in the
      monkey cerebellum, the significant decrease of R in old animals needs to be
      considered from the functional standpoint. Since COX is the terminal enzyme of
      the mitochondrial respiratory chain, the estimation of its activity is regarded
      as a reliable MMC index; thus our findings, by matching preferential
      cytochemistry and morphometry, support the hypothesis that the specific
      functional impairment of enlarged synaptic mitochondria may seriously affect
      information processing and cell-to-cell communication at synaptic junctional
      areas with aging.

PMID- 18328004
TI  - An ultrasensitive assay for diagnosis of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the most
      common cause of dementia. Aging is among the most significant risk factors.
      Today, AD can be diagnosed with certainty only post mortem, detecting insoluble
      beta-amyloid peptide (Abeta) aggregates in the patient's brain tissue. We have
      developed an ultrasensitive assay for early and non-invasive diagnosis of AD.
      This highly specific and sensitive assay uses fluorescence correlation
      spectroscopy (FCS) and is sensitive enough to detect even single aggregates in
      body fluids of AD patients. We investigate the correlation of aggregated Abeta
      concentrations in body fluids with clinical symptoms of AD.

PMID- 18328005
TI  - A novel Zip2 Gln/Arg/Leu codon 2 polymorphism is associated with carotid artery
      disease in aging.
AB  - Zinc deficiency represents a risk factor for carotid stenosis (CS) development.
      In mammals, members of the ZIP family regulate zinc uptake, and hZip2 is a human
      zinc importer upregulated by zinc depletion. The purpose of this study was to
      investigate the association of a novel Zip2 Gln/Arg/Leu codon 2 polymorphism with
      CS, analyzing 250 CS patients and 259 elderly controls. CS patients showed an
      increased GG genotype frequency (60% vs. 47.5%), and a reduced TT frequency (6%
      vs. 10%) (p < 0.05 by chi(2) test). In conclusion, Zip2 Gln/Arg/Leu polymorphism
      plays a role in the susceptibility to carotid artery disease.

PMID- 18328006
TI  - Enhancing longevity: novel caloric restriction mimetics.

PMID- 18328007
TI  - Alzheimer's disease-like changes in herpes simplex virus type 1 infected cells:
      the case for antiviral therapy.

PMID- 18328008
TI  - Decreased presence of perforated synapses in a triple-transgenic mouse model of
      Alzheimer's disease.
AB  - Transgenic mouse models of Alzheimer's disease (AD) are useful tools to further
      our understanding of AD genotype-phenotype interaction. The triple transgenic
      mice harboring mutant forms of APP/PS1/Tau (3xTg-AD) exhibit beta-amyloid (Abeta)
      plaques (by 6 months of age) as well as neurofibrillary tangles (by 10-12 months
      of age). In this study, we characterized morphological alterations of hippocampal
      synapses obtained from 13-month-old 3xTg-AD and age-matched control (PS1-KI)
      mice. Numeric density of synapses (Nv, number of junctions/microm(3) of tissue),
      average synaptic contact area (S), and synaptic surface density (Sv, total
      synaptic contact area/microm(3) of tissue) were investigated by morphometric
      methods in the AD vulnerable CA1 pyramidal cell layer. Comparisons between 3xTg
      AD and control mice showed no statistically significant differences in any of the
      three parameters; however, a significant decrease (by 28.5%) in the fraction of
      perforated junctional areas (PS) was observed in the 3xTg-AD mice. As PS is a
      reliably indirect index of synaptic plasticity, a decreased PS number might
      represent a subtle and early sign of synaptic dysfunction occurring in the 3xTg
      AD mice, and lend support to the hypothesis that altered synaptic function is a
      critical feature of AD.

PMID- 18328009
TI  - Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I
      trial: a mixed-methods study.
AB  - OBJECTIVES: In this phase I safety trial of tenofovir gel, a candidate vaginal
      microbicide for human immunodeficiency virus (HIV) prevention, a mixed-methods
      design was used to gather acceptability data among women participants. The impact
      of acceptability factors on use of the gel and the relationship between
      qualitative and quantitative acceptability data are explored. METHODS:
      Participants included low-risk, HIV-uninfected, and clinically stable HIV
      infected women. Participants were enrolled into cohorts stratified by HIV
      serostatus, sexual activity, gel concentration, and frequency of use.
      Quantitative data were collected via interviewer-administered structured
      questionnaires. Qualitative data were collected via semistructured small group
      discussions. RESULTS: Although 94% of participants stated they would "probably"
      or "definitely" use tenofovir gel, a range of responses emerged on multiple
      domains relevant to microbicide acceptability during the qualitative discussions.
      Lubrication, leakage, sexual pleasure, and the possibility of covert use were
      central to women's qualitative assessments of tenofovir gel. CONCLUSIONS:
      Quantitative results indicate that tenofovir vaginal gel was acceptable to almost
      all users, while qualitative findings indicate that acceptability is complex,
      varies among users, and is likely shaped by a variety of contextual factors that
      manufacturers will need to consider to optimize use-effectiveness. Because of the
      differences in the qualitative and quantitative responses, the authors argue that
      future trials of candidate microbicides should include strategic collection of
      mixed-methods microbicide acceptability data.

PMID- 18328010
TI  - Gestational diabetes in rural East Africa: a call to action.
AB  - The number of cases of diabetes worldwide has increased significantly in the last
      decade. Characteristically, the incidence of gestational diabetes (GDM) reflects
      the incidence of type 2 diabetes mellitus (T2DM) in the background population,
      which is a warning that a rapid increase in the incidence is to be expected
      concomitant with the already observed increase in the incidence of T2DM. Although
      the majority of all deliveries worldwide take place in the so-called developing
      world, little is known about the prevalence of diabetes in pregnancy in rural
      areas of East Africa. Diabetes in pregnancy has effects on prospects for
      marriage, motherhood, and the role of women in East African society. Furthermore,
      intrauterine exposure to the metabolic environment of maternal diabetes, or GDM,
      is associated with increased risk of altered glucose homeostasis in the
      offspring, beginning in childhood and producing a higher prevalence of GDM in the
      next generation with all burdens and complications being associated with this
      disease. It is reasonable to conclude that more newborn infants each year are
      being exposed to the metabolic environment of diabetes during intrauterine
      development as a result of changing incidence and demographics of diabetes and
      pregnancy. We believe that programs and policies have to be established,
      including organization of the health system to provide care, medicines, and other
      tools necessary for diabetes in pregnancy management, consideration of
      accessibility and affordability of care, education for healthcare workers, and
      education of pregnant and nonpregnant women of reproductive age.

PMID- 18328011
TI  - Catamenial pneumothorax: a case report and review of the literature.
AB  - A 39-year-old woman presented with the chief complaint of right-sided chest
      pressure and shortness of breath with dry cough for 3 days. These symptoms
      coincided with the onset of her menstrual cycle. Her physical examination was
      significant for decreased breath sounds at the right lung base. Her chest x-ray
      showed a moderate sized right pneumothorax extending from the apex to the lung
      base and a small amount of pleural fluid, findings that were verified by chest
      CT. The patient was seen by consultants from the pulmonary,
      obstetrics/gynecology, and thoracic surgery services, who agreed that the
      clinical diagnosis was catamenial pneumothorax, probably associated with thoracic
      endometriosis. The patient was discharged on levonorgestrel/ethinyl estradiol
      tablets, which she opted not to take. Three months later, she had similar
      symptoms that occurred again at the time of menstruation. Her chest x-ray now
      showed a 10% right-sided pneumothorax. Catamenial pneumothorax is a rare
      condition affecting women in their reproductive years. Women with this condition
      most commonly have right-sided pneumothorax. The proper diagnosis is based on
      being aware of the existence of this relatively rare condition and relating the
      symptoms of pneumothorax temporally to the menses.

PMID- 18328012
TI  - Are bipolar mood symptoms affected by the phase of the menstrual cycle?
AB  - BACKGROUND: Evidence suggests gender differences may exist in bipolar disorder,
      and a review of the literature shows that more women than men may experience
      rapid-cycling bipolar disorder. The issues contributing to these gender
      differences are unknown; a number of case reports have indicated the possibility
      of mood changes secondary to hormonal influences during the menstrual cycle. We
      sought to examine the relationship between bipolar disorder and menstrual cycle
      related mood changes. To our knowledge, this is one of the largest samples in the
      literature addressing this issue. METHODS: Outpatient women with bipolar disorder
      I, bipolar disorder II, and not otherwise specified (NOS), between the ages of 18
      and 45, were evaluated. The National Institute of Mental Health Life Chart Method
      p (NIMH-LCM-p) was used for daily mood ratings of depression and mania. Repeated
      measures of ANOVA and t tests were conducted separately for depressive and for
      manic symptom scores. RESULTS: One hundred nineteen women met the age criterion,
      and only 41 women met the rest of the inclusion criteria. In this sample of 41
      women, there was no significant relationship between phases of the menstrual
      cycle (early and late follicular and early and late luteal phases) and changes in
      depression or mania. In an exploratory examination, 8 of 41 women showed a
      numerically higher mean depression score in the luteal phase than in the
      follicular phase; 5 of 41 women showed a numerically higher mean mania score in
      the luteal phase than in the follicular phase of the menstrual cycle.
      CONCLUSIONS: Different phases of the menstrual cycle were unrelated to depression
      and mania in a heterogeneous group of women with bipolar disorder. Prospective
      studies are needed to identify a vulnerable subpopulation in a homogeneous
      clinical sample.

PMID- 18328013
TI  - Development and validation of the Premenstrual Symptoms Impact Survey (PMSIS): a
      disease-specific quality of life assessment tool.
AB  - OBJECTIVE: To develop and validate the Premenstrual Symptoms Impact Survey
      (PMSIS), a brief web-based instrument for evaluating the impact of premenstrual
      symptoms on health-related quality of life (HRQOL). METHODS: An item bank of 68
      questions was administered to a nationally representative sample of 971 women
      using the web, aged 18-45, who experienced regular menstrual cycles in the past 3
      months, were not currently pregnant or breastfeeding, and were not being treated
      or taking medications for depression-related disorders in the last 2 years. Item
      reduction was performed using forward stepwise linear regression of an overall
      symptom severity score onto item scores. Three standards were used to validate
      the instrument: (1) the American College of Obstetricians and Gynecologists
      retrospective diagnostic criteria for identifying participants "at risk" for
      clinically significant premenstrual syndrome (PMS), (2) the American Psychiatric
      Association's Diagnostic and Statistical Manual of Mental Disorders retrospective
      diagnostic criteria for identifying participants at risk for premenstrual
      dysphoric disorder (PMDD), and (3) the Medical Outcomes Study Short Form (SF-12)
      Health Survey. RESULTS: Six items met entry criteria in the model. Approximately
      6.0% of the participants were identified as being at risk for PMDD, and 17.3%
      were identified as being at risk for clinically significant PMS. PMSIS scale
      score differed significantly between participants who were and were not at risk
      for PMDD/clinically significant PMS. PMSIS scale score also differed
      significantly between participants having either high, average, or low HRQOL as
      defined by SF-12 physical and mental component summary scores. CONCLUSIONS: These
      results demonstrate that the PMSIS has excellent discriminative ability to detect
      differences in groups that are known to differ in terms of clinical criteria. The
      PMSIS can be used to educate consumers about the impact of their symptoms on QOL.

PMID- 18328014
TI  - Flaxseed reduces total and LDL cholesterol concentrations in Native American
      postmenopausal women.
AB  - OBJECTIVE: The objective of the study was to investigate the extent to which the
      daily incorporation of approximately 30 g of flaxseed, a rich source of lignans,
      omega-3 fatty acids, and fiber, for a period of 3 months into the diet of Native
      American postmenopausal women positively affects their lipid profiles. METHODS:
      Fifty-five mild to moderately hypercholesterolemic (> or =5.1 to < or =9.8
      mmol/L) Native American postmenopausal women were randomly assigned to control
      (A), flaxseed (B) or flaxseed + additional oat bran fiber (C) groups. Overnight
      fasting venous blood was collected at baseline and at the end of the treatment
      period to analyze lipid parameters. RESULTS: Dietary flaxseed supplementation
      lowered total cholesterol and low-density lipoprotein cholesterol (LDL-C) by
      approximately 7% and 10%, respectively. However, the levels of high-density
      lipoprotein (HDL) and triglyceride remained unaltered. No changes were observed
      in other clinical and hematological parameters. CONCLUSIONS: The results of the
      present study indicate that Native American postmenopausal women benefit from
      regular consumption of flaxseed by reducing their risk of cardiovascular disease
      as seen from lowered LDL-C and total cholesterol levels.

PMID- 18328015
TI  - Toward optimal health: Dr. Kelly Brownell discusses [corrected] the influence of
      the environment on obesity. Interview by Jodi R. Godfrey.

PMID- 18328016
TI  - An HIV/AIDS crisis among African American women: a summary for prevention and
      care in the 21st century.
AB  - The meeting, HIV/AIDS and African American Women: A Consultation Supporting CDC's
      Heightened National Response to the HIV/AIDS Crisis among African Americans,
      provided a forum to address gaps in prevention and HIV/AIDS infection for African
      American women. Health researchers, community-based organization leaders, and
      representatives from both healthcare and non-healthcare sectors took this
      opportunity to discuss and develop a variety of priorities and suggestions for
      HIV/AIDS prevention. Four focus areas were provided for meeting attendees to
      promote discussion and strategy development. The resulting list of priorities and
      suggestions for HIV/AIDS prevention may provide future steps for researchers,
      communities, and physicians to increase prevention and decrease infection rates.
      Novel, innovative, and participatory approaches are needed within and outside the
      public arena to decrease the gaps in HIV/AIDS prevention for African American
      women.

PMID- 18328018
TI  - In memoriam: Oleg Georgovitch Gazenko, M.D. 1918-2007.

PMID- 18328019
TI  - What's next on the horizon?

PMID- 18328020
TI  - Telethinking with Arnauld Nicogossian, M.D. Interview by Vicki Glaser.

PMID- 18328021
TI  - Medical tourism.

PMID- 18328022
TI  - Systematic human factors evaluation of a teledermatology system within the U.S.
      military.
AB  - The benefits of telemedicine systems within the U.S. military have been widely
      recognized. However, a number of telemedicine systems have encountered resistance
      and have failed to be adopted and widely used. The purpose of the present project
      was to use a human factors analysis to characterize the facilitators and
      impediments to the use of a teledermatology system. More specifically, the goal
      was to investigate areas such as training, workload distribution, and
      communication between team members because these topics can be broadly classified
      as human factors issues. Across different sites, structured interviews were
      administered to three user groups within the system (i.e., consult managers,
      primary care managers who are comparable to civilian primary care physicians, and
      dermatologists). All three user groups reported that system support, speed,
      personal benefits, and increased education and experience were facilitators to
      system use; impediments were usability problems and insufficient training.
      However, each user group also identified unique facilitators and impediments. For
      example, users at the referring site (consult managers and primary care managers)
      focused on workload distribution among team members and the importance of onsite
      support as facilitators. In contrast, key facilitators for physicians (primary
      care and dermatologists) were effective communication, professional benefits, and
      increased quality of patient care. Human factors issues are critical for
      successful telemedicine systems and user issues may vary across user groups. The
      method reported herein provides guidance for development of new telemedicine
      systems and evaluation of existing telemedicine systems to increase adoption and
      usage.

PMID- 18328023
TI  - Counseling center-based tele-mental health for students at a rural university.
AB  - Students attending rural academic institutions often have no immediate access to
      psychiatrists to supplement on-site Counseling Center (CC) services. Because the
      Medical College of Georgia (MCG) could not cost-effectively provide on-site
      psychiatry services to Georgia Southern University (GSU) students, the two
      institutions explored telehealth services delivered by supervised Psychiatry
      residents using Web-based videoconferencing on MCGs virtual private network. GSU
      counselors completed client severity rating forms. CC clients in ongoing therapy
      who were judged to be in need of psychiatric services were referred to the Tele
      clinic (TC). CC counselors referred the most challenged students to TC according
      to total distress score on intake, clinician intake assessment of client
      difficulty, and client need for medications. After seeing the clients in TC, MCG
      residents also completed GSU CC client severity rating forms. Post-intake and
      satisfaction surveys already in use at the GSU CC were completed both by CC
      clients not in TC and by CC clients jointly enrolled in TC. TC and CC populations
      were compared by gender, race, past mental health treatment, past psychiatric
      hospitalization, and past and current use of psychotropic drugs. Telepsychiatry
      conducted using low bandwidth videoconferencing successfully supplemented GSU CC
      mental healthcare, especially for clients with the most serious problems, and did
      so without travel from campus and within the milieu of daily student life. Cost
      effective telepsychiatry services can successfully supplement management of
      students with mental health issues who attend rural, smaller, and/or resource
      challenged academic institutions.

PMID- 18328024
TI  - What Do Spanish physicians believe and expect about telemedicine? Results of a
      Delphi-based survey.
AB  - The aim of this Delphi-based study was to evaluate the intention of Spanish
      physicians to accept and use telemedicine as a future useful tool in daily
      practice. An online Delphi questionnaire was answered by 985 physicians (966 in
      the second round), representatives from rural and urban areas of the entire
      country (generalists, internists, cardiologists, endocrinologists, and
      nephrologists). The participants were 65% males, with a mean age of 46.7 years
      old and 20.3 years in the profession, mostly coming from primary care centers
      (91.8%) of urban Spanish areas (72.8%). Some responders (56.4%) reported lack of
      Internet use at work and 80.2% never participated in a telemedicine project, but
      80.9% said they would be interested in participating in the future. As for the
      benefits of telemedicine, the specialties perceived as the most benefited were
      cardiology, followed by general medicine, pediatrics, and emergency services. The
      main reported difficulty for telemedicine implementation was the opinion that
      patients prefer the physical contact with physicians (77.8% of responders).
      Interviewed participants expressed strong interest in future telemedicine
      projects related to online training, distance control of chronic diseases, online
      communication among specialists, and real-time transmission of images and
      information. Most Spanish physicians have not implemented telemedicine in
      clinical practice, but they would be interested in future applications such as on
      line training or disease control, although they still prefer physical patient
      contact.

PMID- 18328025
TI  - Regional and international prenatal telemedicine network for computerized
      antepartum cardiotocography.
AB  - The objective of this work was to review the activity of TOCOMAT, a system for
      antepartum cardiotocographic telemonitoring. Nine peripheral units recorded the
      traces, transmitted them via modem to the University operation center, where the
      computerized analysis was performed, and received the medical report within a few
      minutes, via fax or e-mail. Traces were classified as reassuring, nonreassuring,
      or pathological. The parameters of computerized analysis were grouped together
      for each week of gestation. The perinatal outcome was also evaluated. In 5 years,
      5830 traces were analyzed: 4372 (75%) from 1344 high-risk patients and 1458 (25%)
      from 529 patients at apparent low risk. The system allowed the identification of
      high-risk patients (32.8% with nonreassuring traces and 7.1% with pathologic
      traces) and lowrisk patients (16.3% with nonreassuring traces and 4.3% with
      pathologic traces) that required further evaluation. The neonatal outcome was
      good overall. At each week of pregnancy, the mean values of computerized
      parameters resulted in normal ranges. The TOCOMAT system allowed a
      decentralization of prenatal surveillance and improved the patients quality of
      life and the level of prenatal care.

PMID- 18328026
TI  - Development of a portable device for telemonitoring of snoring and obstructive
      sleep apnea syndrome symptoms.
AB  - The First Intensive Balkan Telemedicine and e-Health Seminar was held in the war
      ravaged capital of Kosova, Prishtina, in 2002. This event was created under the
      auspices of the International Virtual e Hospital (IVeH). This organization, the
      brain child of Rifat Latifi, M.D., was established with the intent to establish a
      medical capability using telemedicine in an environment where the health
      infrastructure had been totally destroyed by war. Recently, the IVeH opened six
      regional telemedicine centers in Kosova. These centers are in the cities of
      Gjilan, Prizren, Gjakove, Peja, Skenderaj, and Mitrovica. These centers cover the
      entire country through a telemedicine network. Recently, the Second Intensive
      Seminar was organized and held October 2123, 2007, in Tirana, Albania. It was
      organized to broaden the concept of telemedicine and e-health in the Balkans
      region, and to introduce telemedicine in Albania, which was an ideal choice for
      holding the seminar. The seminar represented a significant step for Albania as it
      embraces the concept of telemedicine. These important events have shaped
      telemedicine development in the Balkans and are serving as a model for the rest
      of the South Eastern European countries to embrace telemedicine and e-health.
      This paper summarizes the events of this second seminar and addresses the
      importance telemedicine has for the region.

PMID- 18328027
TI  - Health technology assessment of a homecare device for telemonitoring and
      telerehabilitation for patients after hand transplantation.
AB  - Hand rehabilitation requires continuous and frequent monitoring of the
      functionality in order to assess therapy and/or refine it. In order to contain
      costs for the rehabilitation program, a telehomecare rehabilitation system is
      suitable. The purpose of this paper was to describe the setup and configuration
      of a homecare device for telemonitoring/telerehabilitation of patients who
      underwent hand transplant. The telehomecare device allows the assessment of
      dynamics and kinematics of hand function by integrating dedicated software in two
      components. The first was a commercial glove, the HumanGlove by Humanware (Pisa,
      Italy). The second was a set of instruments for the measurement of digit force
      using an Instrumented Keyboard and an Instrumented Mouse-Like device. The
      software integrating the devices is composed of two modular components. The first
      is to drive the devices; the second is for the data-analysis and display. The
      methodology was validated at the Istituto Superiore di Sanit (the Italian
      National Institute of Health) in the framework of an Italian National Project,
      funded by the Ministry of Health.

PMID- 18328028
TI  - Telemonitoring and telerehabilitation of patients with Parkinson's disease:
      health technology assessment of a novel wearable step counter.
AB  - Step counting is an important index of motion in telemonitoring. One of the most
      diffused wearable systems, designed for this purpose, is the pedometer. The
      accuracy of commercial pedometers has been reported in the literature. Several
      limits have been found in many commercial systems both in healthy subjects and in
      people with disabilities. Furthermore, commercial pedometers lack
      interoperability. This paper introduces a new wearable system for step counting
      for telemonitoring applications. This system is based on a wearable device with a
      force-sensing resistor. It is affixed on the gastrocnemius muscle for monitoring
      muscular expansion correlated with the gait. The data exchange is assured by the
      XTR-434H (Aurel, FC, Italy) telemetric system. The proposed gastrocnemius
      expansion measurement unit (GEMU) was tested on 5 subjects with Parkinsons
      disease at Level 3 of the Tinetti test of unbalance. Ten repetitions of 500 steps
      with three different speeds (fast, slow, and normal) were performed. The mean
      error was <0.5%. Results also showed that GEMU performed better than an
      accelerometer unit (considered in the literature the best solution for this
      disability). The study showed that GEMU had a high performance in subjects with
      Parkinsons disease, causing a high degree of unbalance that confounded motion
      style. The next phase will be the optimization of GEMU for long-term medical
      applications at the patients home.

PMID- 18328039
TI  - Persistent atrial fibrillation worsens heart rate variability, activity and heart
      rate, as shown by a continuous monitoring by implantable biventricular pacemakers
      in heart failure patients.
AB  - BACKGROUND: Atrial fibrillation (AF) induces loss of atrial contribution, heart
      rate irregularity, and fast ventricular rate. OBJECTIVES: The objectives of the
      study were to accurately measure AF incidence and to investigate the mutual
      temporal patterns of AF and heart failure (HF) in patients indicated to cardiac
      resynchronization therapy. METHODS: Four hundred ten consecutive patients (70%
      male, age 69 +/- 11) with advanced HF (NYHA = 3.0 +/- 0.6), low ejection fraction
      (EF = 27 +/- 9%), and ventricular conduction delay (QRS = 165 +/- 29 ms) received
      a biventricular pacemaker. Enrolled patients were divided into two groups: G1 =
      249 patients with no AF history, G2 = 161 patients with history of
      paroxysmal/persistent AF. RESULTS: In a median follow-up of 13 months, AF
      episodes longer than 5 minutes occurred in 105 of 249 (42.2%) G1 patients and 76
      of 161 (47.2%) G2 patients, while AF episodes longer than one day occurred in 14
      of 249 (5.6%) G1 patients and in 36 of 161 (22.4%) G2 patients. Device
      diagnostics monitored daily values of patient activity, night heart rate (NHR),
      and heart rate variability (HRV). Comparing 30-day periods before AF onset and
      during persistent AF, significant (P < 0.0001) changes were observed in patient
      activity, which decreased from 221 +/- 13 to 162 +/- 12 minutes, and in NHR,
      which increased from 68 +/- 3 to 94 +/- 7 bpm. HRV significantly decreased (from
      75 +/- 5 ms before AF onset to 60 +/- 6 ms after AF termination). NHR during AF
      was significantly (P < 0.01) and inversely correlated (R(2)= 0.73) with activity,
      with a significant lower activity associated with NHR >or= 88 bpm. CONCLUSION: AF
      is frequent in HF patients. Persistent AF is associated with statistically
      significant decrease in patient activity and HRV and NHR increase.

PMID- 18328040
TI  - Dimensions of informal care in Greece: the family's contribution to the care of
      patients hospitalized in an oncology hospital.
AB  - AIMS AND OBJECTIVES: This study aims to explore the kind and frequency of care
      provided to hospitalized cancer patients by relatives and the reasons for
      providing this care. BACKGROUND: Informal care is a common phenomenon across many
      countries. In Greece, informal caring activities occur in most hospitals.
      Patients' relatives stay by their bedside for long hours and assist with care.
      This phenomenon is highly correlated with the nursing staff shortage. METHOD:
      This study was carried out in a Greek oncology hospital. The sample consisted of
      150 informal caregivers. We used a 37-item questionnaire called In-Hospital
      Informal Care Questionnaire Acute Care. RESULTS: The participants provide
      substantial help to their patients daily. On average, they stay by their bedside
      for 20.23 hours in a 24-hour period. Additionally, 104 participants stated that
      they hire a privately paid patient's helper. The relatives stay by their
      patients' bedside for various reasons such as: (1) severity of the condition; (2)
      providing psychological support; (3) family tradition; (4) because they do not
      believe their patients are safe in the hospital without their supervision; or (5)
      the nursing staff shortage. CONCLUSIONS: The participants offer informal care
      that reflects specific nursing duties. We could argue that Greek hospitals 'use'
      relatives as unpaid labour to compensate for the nursing shortage. It is
      disquieting that usually someone from the hospital staff suggests to the
      relatives to stay at the patient's bedside even after visiting hours or to hire a
      private paid patient's helper. This implies that the staff considers such
      contribution necessary. RELEVANCE TO CLINICAL PRACTICE: The findings show that
      relatives perform daily tasks that nurses should be performing. They indicate
      that the hospital should introduce specific staffing policies for reducing
      families' burden. Our findings could influence future staffing plans of nursing
      managers, policy makers or health authorities.

PMID- 18328041
TI  - The European Male Ageing Study (EMAS): design, methods and recruitment.
AB  - Life expectancy is increasing in most developed countries, in part due to
      improved socioeconomic conditions and in part to advances in healthcare. It is
      widely acknowledged that the promotion of healthy ageing by delaying, minimizing
      or preventing disabilities or diseases is one of the most important public health
      objectives in this century. In contrast to the menopausal transition in females,
      we know relatively little about the contribution of androgens and anabolic
      hormones to the quality of ageing in men. The European Male Ageing Study (EMAS)
      is a multicentre prospective cohort designed to examine the prevalence, incidence
      and geographical distribution of gender-specific and general symptoms of ageing
      in men, including their endocrine, genetic and psychosocial predictors. Men aged
      40-79 years were recruited from eight European centres: Florence (Italy), Leuven
      (Belgium), Lodz (Poland), Malmo (Sweden), Manchester (UK), Santiago de Compostela
      (Spain), Szeged (Hungary) and Tartu (Estonia). Subjects were recruited from
      population registers and those who agreed to take part completed a detailed
      questionnaire including aspects of personal and medical history, lifestyle
      factors and sexual function. Objective measures of body size, cognition, vision,
      skeletal health and neuromuscular function were obtained. Blood and DNA specimens
      were collected for a range of biochemical and genetic analyses. After an average
      of 4 years, it is planned to resurvey the participants with similar assessments.
      A total of 3369 men with a mean age of 60 +/- 11 years were recruited. The mean
      centre response rate was 43%, and highest in those aged 50-59 years. Those who
      participated were marginally younger than those who were invited but declined to
      participate (60.0 vs. 61.1 years). Participants left education slightly later
      than a sample of non-participants, though there were no consistent differences in
      levels of general health, physical activity, or smoking. EMAS will provide new
      population-based data concerning the main features that characterize ageing in
      men and its critical determinants, particularly with reference to age-related
      changes in hormone levels. Such information is an important prerequisite to
      develop effective strategies to reduce age-related disabilities and optimise
      health and well-being into old-age.

PMID- 18328042
TI  - Microflora of the seminal fluid of healthy men and men suffering from chronic
      prostatitis syndrome.
AB  - Chronic prostatitis syndrome (CPS) is a common urologic condition that many
      clinicians find difficult to diagnose and treat effectively. The information
      about the composition of the flora of the seminal fluid in healthy men and
      patients with CPS is limited. The aim of this study was to define the microbial
      communities present in the seminal fluid of healthy men and patients with CPS and
      at in vitro detection of decomplementary activity (DCA) phenotypes of isolates
      along with their comparison with isolates from patients with or without CPS. The
      bacteriological study was carried out to 48 healthy men and 60 men with CPS.
      Culture specimens were spread on various selective media. Bacterial DCA was
      tested by measuring the decrease in complement activity (CH(50)) under the
      influence of culture supernatants. The most common isolates in both groups were
      coryneforms, lactobacilli, coagulase-negative staphylococci, micrococci and
      streptococci. Enterobacteriaceae, enterococci and Staphylococcus aureus were
      isolated only from the CPS group. The organisms from seminal fluid of healthy men
      exerted DCA at 3.56 +/- 2.15; 2.47 +/- 1.23 and 4.36 +/- 2.2 anti-CH(50) for
      staphylococci, micrococci and diphtheroids respectively. The DCA of
      staphylococci, coryneforms, Enterobacteriaceae, enterococci and micrococci from
      CPS group were 12.8 +/- 2.1 (p < 0.05), 4.4 +/- 3.6 (p > 0.05), 16.8 +/- 2.1, 7.2
      +/- 1.9 and 11.6 +/- 3.3 (p < 0.05) anti-CH(50) respectively. The data obtained
      in this study testify the microecological disorders in microbiota of seminal
      fluid in CPS.

PMID- 18328043
TI  - The meaning of caring for people with malodorous exuding ulcers.
AB  - AIM: This paper is a report of a study to illuminate the meaning of caring for
      people with malodorous exuding ulcers. BACKGROUND: Managing ulcers is complicated
      and consensus on assessment and treatment difficult to reach. Nurses need
      knowledge and skills to provide good care. They must stay close and be exposed to
      contamination and suffering. They must provide care without violating patients
      and we need to further explore this challenge. METHOD: A convenience sample of
      ten participants was recruited. Participants had experience of caring for people
      with malodorous exuding ulcers and were employed in primary health or hospital
      care in Sweden. Narrative interviews were conducted during late 2002 to early
      2005 and interpreted using a phenomenological-hermeneutic method. FINDINGS:
      Themes were formulated: 'Facing the wound' when nurses reveal what is meant to be
      concealed and perceive patients' vulnerability; 'Facing one's own
      defencelessness' when feeling invaded, helpless and ashamed; 'Struggling to
      shield one's own defencelessness' was achieved by striving to be in control,
      striving to endure and seeking a way out. 'Struggling to shield patients'
      vulnerability' was about alleviating patients' additional suffering by striving
      to spare patients, pushing boundaries, making uncomfortable decisions and sharing
      togetherness. When failing to shield their own defencelessness and patients'
      vulnerability, nurses run the risk of experiencing desolation. CONCLUSION:
      Physical proximity and bodily suffering affect nurses. Caring for people with
      ulcers calls for improved interprofessional cooperation in order to provide the
      best treatments and care. Further education for these nurses is needed, as well
      as support from managements and organizations.

PMID- 18328044
TI  - Bacterial invasion of dentinal tubules beneath apparently intact but
      hypomineralized enamel in molar teeth with molar incisor hypomineralization.
AB  - BACKGROUND: The most common problems for a patient with molar incisor
      hypomineralization (MIH) are the collapse of enamel and cavitations, loss of
      fillings, and secondary caries, but most of all, severe hypersensitivity.
      OBJECTIVE: The aim of this paper was therefore to histologically study possible
      bacterial invasion of dentinal tubules beneath apparently intact, but
      hypomineralized enamel in permanent molars with MIH. MATERIAL AND METHODS: Five
      extracted permanent first molars diagnosed with MIH were fixated, demineralized,
      and sagittally serially sectioned in a bucco-lingual direction in a microtome
      with a thickness of 4-5 microm. Sections were stained with a modified Brown and
      Benn staining for bacteria, unstained sections were analysed in field emission
      SEM. RESULTS: Stained sections from the cuspal areas, below the hypomineralized
      enamel, the staining indicated the presence of bacteria in the dentinal tubules.
      The HTX staining showed that the pulp in sections without any findings was normal
      and free from bacteria or infiltrates from inflammatory cells. In sections where
      bacteria were found in the cuspal areas or deeper in the dentin, a zone of
      reparative dentin was found, and in sections from one tooth, the coronal pulp
      showed an inflammatory reaction with inflammatory cells. In sections adjacent to
      those without any bacterial staining, the SEM analyses revealed empty dentinal
      tubules without any odontoblast processes or signs of bacteria. When odontoblast
      processes were found, the dentinal tubules were filled with bacteria located on
      the surface of the odontoblast processes. In some areas, a large number of
      tubules were found with bacteria. No bacteria were found close to the pulp. The
      odontoblast processes appeared larger in areas where bacteria were found.
      CONCLUSIONS: The presence of bacteria in the dentinal tubules and inflammatory
      reactions in the pulp indicate that oral bacteria may penetrate through the
      hypomineralized enamel into the dentin, thus possibly contribute to
      hypersensitivity of teeth with MIH.

PMID- 18328045
TI  - Solitary median maxillary central incisor syndrome occurring together with
      oromandibular-limb hypogenesis syndrome type 1: a case report of this previously
      unreported combination of syndromes.
AB  - BACKGROUND: Solitary median maxillary central incisor syndrome is a unique
      developmental abnormality, involving the central incisor tooth germs, occurring
      with and without systemic involvement. This syndrome has been recorded in
      association with many other midline developmental anomalies and several known
      syndromes. Its presence, together with oromandibular-limb hypogenesis syndrome
      type 1, has not previously been reported. CASE REPORT: A 3-year-old girl was
      presented with early childhood caries and a solitary median maxillary central
      incisor. She had a median submucosal cleft palate and severe micrognathia with
      hypoglossia. In addition, she had short stature, eating difficulty, and hearing
      and speech problems. Comprehensive dental treatment for severe early childhood
      caries was accomplished with a 3-month follow-up appointment to monitor the oral
      health. The multidisciplinary consultation important for further management has
      been established. CONCLUSION: The results suggested that when a solitary median
      maxillary incisor tooth presents, a paediatrician and a geneticist should be
      asked to carefully examine the patient for other craniofacial malformations and
      especially midline systemic problems.

PMID- 18328046
TI  - Body adiposity status in teenagers and snacking habits in early childhood in
      relation to approximal caries at 15 years of age.
AB  - BACKGROUND: The prevalence of overweight and obesity in children is steadily
      increasing in many countries. Dental caries and obesity are both multifactorial
      diseases and are associated with dietary habits. OBJECTIVE: The purpose of this
      study was to investigate the relationship between body weight status in
      adolescents and snacking habits in early childhood to approximal caries
      prevalence at 15 years of age. METHODS: This study is part of a series of surveys
      of oral health in children followed from the ages of 1 year to 15 years. Body
      adiposity status was estimated at 13.5-16.4 years using the International Obesity
      Task Force cut-off values [age-specific body mass index (isoBMI)]. Information
      about snacking habits in early childhood was collected from interviews conducted
      at 1 year and 3 years. Approximal caries information was obtained from bitewing
      radiographs at 15 years. Data related to isoBMI and approximal caries were
      available in 402 teenagers. RESULT: Adolescents with isoBMI > or = 25 (n = 64)
      had an approximal caries prevalence that was a mean of 1.6 times higher than
      those with isoBMI < 25 (n = 338) (4.64 vs. 2.94; P = 0.014). Furthermore,
      children's snacking habits at an early age were associated with approximal caries
      at 15 years. CONCLUSION: Overweight and obese adolescents had more approximal
      caries than normal-weight individuals. Moreover, the frequent consumption of
      snacking products during early childhood appears to be a risk indicator for
      caries at 15 years. Future preventive programmes should therefore include, on a
      multidisciplinary level, strategies to prevent and reduce both obesity and dental
      caries at an early age.

PMID- 18328047
TI  - Sucking habits in childhood and the effects on the primary dentition: findings of
      the Avon Longitudinal Study of Pregnancy and Childhood.
AB  - INTRODUCTION: Most previous research on non-nutritive sucking habits has been
      cross-sectional in nature. This study determined the prevalence of non-nutritive
      sucking habits and the effects on the developing dentition within a longitudinal
      observational cohort. METHODS: The Children in Focus group of the Avon
      Longitudinal Study of Pregnancy and Childhood study was studied. Questionnaire
      data on non-nutritive sucking habits were collected on the children at 15 months,
      24 months, and 36 months of age. Dental examinations were performed on the same
      children at 31 months, 43 months, and 61 months of age. RESULTS: At 15 months,
      63.2% of children had a sucking habit, 37.6% used just a dummy, and 22.8% used a
      digit. By 36 months, sucking had reduced to 40%, with similar prevalence of dummy
      and digit sucking. Both habits had effects on the developing dentition, most
      notably in upper labial segment alignment and the development of anterior open
      bites and posterior crossbites. CONCLUSIONS: The majority of children had non
      nutritive sucking habits up until 24 months of age. Both digit and dummy sucking
      were associated with observed anomalies in the developing dentition, but dummy
      sucking habits had the most profound influence on the anterior and posterior
      occlusions of the children.

PMID- 18328048
TI  - Fear of blood, injury, and injections, and its relationship to dental anxiety and
      probability of avoiding dental treatment among 18-year-olds in Norway.
AB  - BACKGROUND: More knowledge about the relationship between blood-injury-injection
      phobia (BIIP) and dental anxiety (DA) may give new clinically relevant
      information in the assessment and management of children with DA. OBJECTIVE: The
      aims of this study were to explore the relationships between BIIP and DA, and to
      explore to what extent the two subtypes of BIIP in combination with DA are
      related to self-reported probability of avoiding dental treatment if a dental
      injection is needed. METHODS: The subjects were a random sample of 1385 18-year
      olds attending high schools in a county of Norway, and the data were collected by
      use of questionnaires completed in classrooms. The survey instruments applied
      were Dental Fear Survey, Injection Phobia Scale-Anxiety, and Mutilation
      Questionnaire. RESULTS: About 11% of the subjects with DA and subtypes of BIIP,
      respectively, reported high probability of avoiding dental treatment in a
      situation where a dental injection was possibly needed. In multiple regression
      analysis, only DA contributed to self-reports of high probability of avoiding
      dental treatment. CONCLUSION: The results indicate that among adolescents, BIIP
      is relatively often connected with DA. Clinical implications are discussed.

PMID- 18328049
TI  - Midazolam conscious sedation in a large Danish municipal dental service for
      children and adolescents.
AB  - OBJECTIVE: The aim of this study was to describe the introduction and the first
      six years use of midazolam for conscious sedation in a municipal dental service
      in Denmark. METHODS: In 1998, all dentists were introduced to midazolam conscious
      sedation. A sedation chart was filled in for each session, and parents'
      assessment was obtained. In 2004, all clinical materials were collected. RESULTS:
      Six hundred and eighty sessions were performed; 63.7% of the children were
      between 2 and 6 years of age; 88.5% belonged to American Society of
      Anesthesiologists grade 1; 74.8% of the sedations performed used the oral route
      of administration. Restorations were performed during 60.3% of the sessions, and
      extractions during 38.4%. Complications during the sessions were rare, the most
      frequent being double vision (6.1%), hiccups (2.7%), and paradoxical reaction
      (2.0%). Using Wilton's sedation scale, 42.9% were calm and 27.7% were agitated
      during treatment, whereas after treatment 61.7% were calm; 80.4% of the parents
      were very positive towards this sedation method. CONCLUSION: Sedation with
      midazolam for dental treatment of children with dental fear and anxiety is a
      feasible and an efficient method with a low rate of complications. It can
      probably reduce the need for dental treatment under general anaesthesia.

PMID- 18328050
TI  - Stainless steel crown versus modified open-sandwich restorations for primary
      molars: a 2-year randomized clinical trial.
AB  - OBJECTIVE: The aim of this study was to investigate the clinical performance and
      survival of stainless steel crown (SSC) restoration and modified open-sandwich
      technique using resin-modified glass ionomer cement. DESIGN: Randomized clinical
      trial. SETTING: General dental practice. MATERIALS AND METHODS: A total of 87
      children aged 4-7 years at baseline with one or more primary molars that have
      undergone pulp therapy were randomly assigned to receive either SSC or modified
      open-sandwich restoration. One hundred and sixty restorations were placed and
      evaluated after 6, 12, 18, and 24 months using the Ryge criteria. RESULTS:
      Comparable survival rates were observed for both SSC and modified open-sandwich
      restoration. With only four SSCs and six modified open-sandwich restorations
      failing over 24 months, the survival rates were high for both materials (2-year
      survival rate: 95.0% for SSCs and 92.5% for modified open-sandwich restorations).
      Significantly better gingival health (P < 0.05) was observed for the modified
      open-sandwich restorations compared with SSCs, as only one modified open-sandwich
      restoration was rated Charlie compared to 13 SSCs. No significant differences
      were observed between the two materials for marginal integrity, proximal contact,
      occlusion, or recurrent caries. CONCLUSION: The 2-year results indicated that the
      modified open-sandwich restoration is an appropriate alternative to SSC in
      extensive restorations, particularly where aesthetic considerations are
      important.

PMID- 18328051
TI  - Gender, ethnicity, culture and social class influences on childhood obesity among
      Australian schoolchildren: implications for treatment, prevention and community
      education.
AB  - The aim of the study was to explore the associations between obesity, weight
      perceptions and gender, ethnicity, culture and social class in a large national
      study of Australian school children. Primary and high schools (N = 47) were
      recruited from every state and territory of Australia and included 7889 children
      from government, private and Catholic schools (82% response rate) in August
      November, 2006. The socioeconomic status (SES) of schools was based on a
      government survey of total family income. A questionnaire completed by students,
      measured demographic details of gender, age, weight perceptions and
      ethnic/cultural background. Height and weight were measured by trained research
      assistants. Outcome measures included body mass index (BMI), prevalence of
      obesity, overweight, weight perceptions. Prevalence of obesity was 6.4% of males
      and 5.6% of females in primary school students (P = 0.34). More high school males
      were obese than females (7.7% vs. 5.7%, P = 0.001). Obesity was more prevalent
      among students from Pacific Islander backgrounds. Adolescents who were most
      likely to be obese were boys and girls of low SES or Pacific Islander or Middle
      Eastern/Arabic background. The least likely to be obese were Anglo/Caucasian or
      Asian students and in particular, the girls. Obese female adolescents from
      Aboriginal, Middle Eastern/Arabic and Pacific Islander backgrounds were less
      likely than their Caucasian or Asian peers to perceive themselves as 'too
      fat'.Those working in clinical, community or educational settings with young
      people and in particular, obese young people, should be aware that obesity is
      likely to be more prevalent, more culturally acceptable and perhaps more
      desirable among children and teens from low SES communities and/or Middle Eastern
      and Pacific Islander backgrounds. Health and social work professionals should be
      careful not to exaggerate the risks of overweight or obesity or inadvertently
      create weight concerns among young people. The different body image perceptions
      identified in this study should be taken into account when planning clinical,
      community or preventive initiatives among children or adolescents from varying
      ethnic groups.

PMID- 18328052
TI  - Exploring the impact of group work and mentoring for multiple heritage children's
      self-esteem, well-being and behaviour.
AB  - Findings are reported from a study of an innovative Multiple Heritage Service in
      Sheffield (UK) which provides, inter alia, individual mentoring for young people
      and school-based group sessions on cultural heritage, dealing with racism and
      enhancing well-being. Group work, undertaken between November 2005 and December
      2006, was evaluated by a before/after design with 43 children aged from 8 to 15
      attending five different groups (response rate 77%), using three well-established
      and validated measures. There were improvements on the Rosenberg Self-esteem
      Scale from 31.4 to 33.0 (P = 0.005) with more improvement among younger children
      and boys (P = 0.004 and P = 0.001); and well-being as measured by the GHQ12
      improved from 1.5 to 0.8 (P = 0.111) with more improvement among older children
      (P = 0.026). On the third measure of problem behaviour (the Strengths and
      Difficulties Questionnaire), there was an improvement from 12.4 to 12.1 (P =
      0.716), but there was no improvement at all for girls. Mentoring was evaluated by
      telephone interviews between June and October 2006 with 14 mothers whose children
      had just completed, or were nearing completion of, mentoring (response rate 70%).
      Overall, the mothers' evaluations were highly positive: two-thirds commended the
      service on the positive impact on their children's well-being and happiness
      (including all the mothers of daughters); a half reported positive impacts on
      identity; mothers commended the positive role model effect same-sex mentors had
      on their children's behaviour; but only a third said mentoring had boosted their
      children's self-esteem.

PMID- 18328053
TI  - The experiences of young people with obesity in secondary school: some
      implications for the healthy school agenda.
AB  - In 1995, the World Health Organisation launched a Global School Health Initiative
      to reduce health risks among young people. In the UK, the National Healthy School
      Programme (HSP) developed as part of a wider government commitment to promoting
      social inclusion. One of the key issues to be tackled by the programme is
      childhood obesity, for obesity is widely argued to be a public health problem for
      which a solution needs to be found. However, the assumption that obesity is
      necessarily problematic and that a higher body weight leads to health problems
      and social exclusion, is not without challenge. Critics of anti-obesity campaigns
      question the significance of weight per se and highlight the potential
      implications of discrediting not only fatness, but also the people who are seen
      as fat. This paper therefore explores the experiences of young people with
      obesity within the secondary school environment in relation to areas of concern
      prioritised by the HSP. The paper draws upon data from a qualitative research
      study involving 18 children and young people, between the ages of 10 and 17. Data
      were generated in focus group discussions and individual interview with
      participants of a community-based obesity intervention programme in South
      Yorkshire, UK. Data collection took place in 2005, and thematic analysis of the
      data was undertaken. Findings suggest that the issues prioritised in the HSP,
      particularly physical exercise and healthy eating, present challenges to young
      people with obesity and can reinforce their vulnerability to bullying in schools
      and contribute to their social exclusion. It concludes that social exclusion is a
      process experienced by, and pertinent to, children and young people, which has
      meaning for their experiences of, and during, childhood and youth. The whole
      school approach of the HSP may fail to adequately address the experiences of
      marginalised and vulnerable groups of young people within schools, challenging
      and undermining the social inclusion agenda in which the programme is grounded
      and contributing to the construction of undesirable, fat, young bodies.

PMID- 18328055
TI  - Lesbian, gay, bisexual and transgender young people's experiences of distress:
      resilience, ambivalence and self-destructive behaviour.
AB  - The research presented in this paper set out to explore the cultural context of
      youth suicide and more specifically any connections between sexual identity and
      self-destructive behaviour, in the light of international evidence about the
      disproportionate risk of suicidal thoughts and suicide attempts in lesbian, gay,
      bisexual and transgender (LGBT) young people. The empirical basis for the paper
      is qualitative research that was carried out in the North West of England and
      South Wales. Focus groups and interviews were conducted with a total of 69 young
      people, with a purposive sample to reflect diversity of sexual identity, social
      class and regional and rural-urban location. The paper presents a thematic
      analysis of the data specifically relating to the experiences of LGBT young
      people. A range of strategies that LGBT young people employ in the face of
      distress are described. These are categorised as resilience, ambivalence and self
      destructive behaviour (including self-harm and suicide). The potential
      implications for health and social care of these strategies include the need for
      ecological approaches and for sexual cultural competence in practitioners, as
      well as prioritisation of LGBT risk within suicide prevention policies.

PMID- 18328056
TI  - Making schools and young people responsible: a critical analysis of Ireland's
      obesity strategy.
AB  - Worldwide reports of an obesity 'epidemic' prompted the Irish government to
      appoint a multidisciplinary Taskforce, whose report was published in May 2005.
      This paper critically analyses the report and its recommendations for reducing
      health risks among families, children and young people. Using a Foucauldian
      perspective, we question the report's individualizing focus and support for a
      strategy which responsibilises schools, families and young people and relies on
      individuals to do 'the right thing'. Specifically, we examine the Taskforce
      recommendations for the education sector, and identify their dependence upon a
      discourse of governmentality, under categories of individualization,
      responsibilization and freedom of choice, participation and techniques for
      management of the self. We conclude that the report fails to address the multi
      faceted and complex nature of obesity, and obscures the social, economic and
      material realities of the lives of pupils and schools.

PMID- 18328057
TI  - Streets ahead on safety: young people's participation in decision-making to
      address the European road injury 'epidemic'.
AB  - This paper reports on Birmingham City Council's Streets Ahead on Safety project
      which aims to improve road safety and quality of life in an area of multiple
      deprivation where 87 000 people from largely Asian, immigrant backgrounds live. A
      third of residents are under 16 years old and 58% self-define their religion as
      Muslim. The area has a poor traffic accident record leading to high levels of
      killed or seriously injured children. Child accidental injury in Europe is
      reaching 'epidemic' proportions, requiring innovative, ameliorative approaches to
      redress. Existing UK school-based road safety initiatives rarely extend beyond
      the 'tokenistic', but this project endeavoured to encourage a highway authority,
      engineers and road safety officers to provide local young people with
      opportunities to participate in decision-making in the belief that the active
      engagement of young service users would lead to more effective and sustainable
      solutions to accident prevention. Embracing the city's ratification of the UN
      Convention on the Rights of the Child (1989), this project promoted young
      people's participation in decision-making around engineering plans for their
      local community. The project included 405 young people aged 9-11 years who
      conducted environmental audits, interactive road safety awareness and citizenship
      training, and engaged as decision-makers. Successful outcomes include increased
      knowledge of road and community safety issues, and the establishment of young
      people as stakeholders in the development of their own safety and active
      engagement with service providers in the development of engineering proposals.
      This paper highlights the potential dynamics of participation and the dilemmas it
      poses for relationships between service users and providers, and outlines some of
      the barriers confronted by young people in learning to be active participants.

PMID- 18328058
TI  - Barriers and facilitators to partnership working between Early Intervention
      Services and the voluntary and community sector.
AB  - Partnership working between health and the voluntary and community sector has
      become an increasing political priority. This paper describes and explores the
      extent and patterns of partnership working between health and the voluntary and
      community sector in the context of Early Intervention Services for young people
      with a first episode of psychosis. Data were collected from 12 Early Intervention
      Services and through semistructured interviews with 47 voluntary and community
      sector leads and 42 commissioners across the West Midlands of England. Most
      partnerships were described as ad hoc and informal in nature although four formal
      partnerships between Early Intervention Services and voluntary and community
      sector organizations had been established. Shared agendas, the ability to refer
      clients onto an organization that could provide a service they could not and
      shared training facilitated partnership working in this context. Barriers to
      closer working included differences in culture such as managing risk, the time
      required to make and maintain relationships and recognition of the advantages of
      remaining a small and autonomous organization. The four more formal partnerships
      were also built on the organizations' experience of working together informally,
      in one case through a specific pilot project. The voluntary and community
      organizations involved were also branches of larger national organizations for
      whom finding sustainable funding was less of an issue. In theoretical terms,
      eight Early Intervention Service: voluntary and community sector partnerships
      were at a stage of 'pre-partnership collaboration', three at 'partnership
      creation and consolidation' and one at 'partnership programme delivery'. The
      empirical data viewed through the lens of the partnership life-cycle model could
      help early intervention services, and voluntary and community sector
      professionals better understand where they are, why they are there and the
      conditions needed to realise the full potential of partnership working.

PMID- 18328059
TI  - A randomized, single-blind, placebo-controlled, split-face study with
      pimecrolimus cream 1% for papulopustular rosacea.
AB  - BACKGROUND: Rosacea is a common inflammatory skin disorder for which the
      pathogenesis is unclear. Currently, there is no cure for rosacea, and it seems
      that standard therapies have focused mainly on minimizing inflammation.
      OBJECTIVES: The aim of this study is to investigate the potential efficacy,
      tolerability and safety profile of 1% pimecrolimus cream for the treatment of
      rosacea. METHODS: Twenty-five patients with papulopustular rosacea were enrolled
      to a randomized, single-blinded, placebo-controlled, split-face trial of
      pimecrolimus cream 1% consisting 4 week treatment and 2 week follow-up period.
      The patients were instructed to apply first the 'left side cream' labelled
      placebo cream (Ultrabase cream, Intendis GmbH, Berlin, Germany) to the left hemi
      face then the 'right side cream' labelled 1% pimecrolimus cream (Elidel; Novartis
      Pharma, Nuremberg, Germany) to the right hemi-face, twice daily. They were
      informed to apply a standard amount of each cream with the fingertip-unit and not
      allowed to use any other agent concomittantly other than sunblock. Clinical
      evaluation and subjective severity assessment were obtained along with
      photographic documentation at baseline, first, second, and fourth weeks of the
      therapy and at the follow-up visit. Rosacea severity score for each sign of
      erythema, papules, pustules, oedema, and telengiectesia were graded from 0 to 3.
      Patients were questioned for the subjective symptoms, overall improvement on
      appearance and side-effects. RESULTS: Twenty-four patients completed the study
      with an exceptional compliance and tolerable safety profile. One patient withdrew
      from the study due to severe flare-up reaction affecting both hemi-faces. The
      mean baseline total rosacea severity scores were 5.06 + 1.29 for both sides and
      reduced to 2.5 +/- 1.06 vs. 3.25 +/- 1.24 on pimecrolimus vs. placebo applied
      sides without the significance (P = 0.06). There was not any significant
      difference concerning each rosacea sign scores and total rosacea severity scores
      except for the significant improvement in erythema score and total rosacea
      severity score obtained on the pimecrolimus-applied hemi-face at 2nd week of
      therapy (P =0.01 and P = 0.03, respectively). The reduction rates of the mean
      subjective severity scores at 4th week were 49.77% vs. 38.89% for pimecrolimus
      vs. placebo, respectively, without a statistical significance (P = 0.15).
      Subjective symptoms responded well in 54.16% of patients concerning pimecrolimus
      application compared with 12.50% for the placebo application. The side-effects
      were mostly transient local irritations. CONCLUSION: Our data implicated that
      pimecrolimus cream is not superior to placebo except for its efficacy on
      erythema. We believe that pimecrolimus cream can be a treatment option for
      rosacea patients with high erythema score for whom an initial accelerated
      improvement is needed. We believe further studies with topical pimecrolimus cream
      on larger study groups with different subtypes and severity of rosacea will
      clarify the potential effect of pimecrolimus cream for the treatment of rosacea.

PMID- 18328061
TI  - Expression studies of missense mutations p.D141Y, p.C275S located in the
      propeptide of von Willebrand factor in patients with type 3 von Willebrand
      disease.
AB  - Missense mutations are not considered a common cause of type 3 von Willebrand's
      disease (VWD), the most severe defect of von Willebrand factor (VWF)
      characterized by undetectable levels of this protein in plasma and platelets.
      Nevertheless, several missense mutations have been identified in these patients.
      In this study, we report the cases of two Italian patients with type 3 VWD, both
      compound heterozygotes for different missense mutations and null alleles,
      p.D141Y/c.2016_2019del and p.C275S/p.W222X. We performed in vitro expression
      studies of the candidate missense mutations, both located in the D1 domain of VWF
      propeptide, to confirm their link with the disease and to understand the
      mechanisms of type 3 VWD responsible in these patients. Mutant and wild-type (WT)
      expression vectors were used for transient transfection and co-transfection
      studies in COS-7 cells. Single construct transfections of both missense mutations
      showed a strongly reduced but detectable secretion of recombinant (r)VWFs
      (approximately 15% of WT), with essentially only dimers being visualized on
      multimeric analysis. As expected, expression of a single construct of either
      mutation with the WT, showed mildly reduced secretion (approximately 40% of WT)
      and a full set of multimers. These expression studies indicate that the two amino
      acids D141 and C275 are key residues in the tertiary structure of the VWF
      propeptide. Their replacement with a tyrosine and a serine, respectively, might
      compromise propeptide folding, affecting both its intracellular survival and its
      capacity to mediate multimerization. Co-expression of hybrid rVWFs confirmed the
      recessive inheritance pattern of these missense mutations.

PMID- 18328062
TI  - Foetal sex determination in maternal blood from the seventh week of gestation and
      its role in diagnosing haemophilia in the foetuses of female carriers.
AB  - The existence of foetal DNA in maternal blood, discovered in 1997, opened new
      possibilities for noninvasive prenatal diagnosis. This includes foetal sex
      assessment by the detection of specific Y chromosome sequences in maternal blood,
      particularly important when a foetus may be affected by an X-linked disorder such
      as haemophilia. This study aims to validate this sex assessment method and to
      test its clinical utility in the diagnosis of 15 potentially affected pregnancies
      in female carriers of haemophilia. In the validation study, 316 maternal blood
      samples from 196 pregnant women at gestations ranging from 5 weeks to 12 weeks
      were analysed. In the clinical study, 15 pregnancies at risk of having a
      haemophilic foetus were tested. All pregnancies in the validation study were
      correctly diagnosed. The accuracy and specificity of the methodology from the
      seventh week of gestation was 100%. The sex of all 15 pregnancies identified as
      being at risk of bearing a haemophilic foetus was correctly diagnosed. Foetal sex
      assessment by detecting specific Y chromosome sequences in maternal blood is now
      routinely used in our hospital because of its high accuracy from the seventh week
      of gestation. Reliable foetal gender determination from maternal blood of
      pregnant women carriers of haemophilia in the first trimester of gestation can
      avoid more conventional, invasive methods of prenatal diagnosis.

PMID- 18328063
TI  - A model for estimating cirrhosis in patients with type 1 autoimmune hepatitis.
AB  - Longstanding cirrhosis has been recognized as a risk factor for the development
      of hepatocellular carcinoma in patients with autoimmune hepatitis (AIH). Thus,
      the accurate determination of cirrhosis is important for prognostication,
      decisions regarding treatment and monitoring of disease progression. The aim of
      this study was to identify independent predictors of cirrhosis and to develop a
      model for estimating cirrhosis in patients with type 1 AIH. METHODS: Using the
      training sample, consisting of 121 patients with type 1 AIH, we retrospectively
      examined independent predictors of cirrhosis and constructed a model for
      estimating cirrhosis. Validation was prospectively performed in the validation
      sample, consisting of 35 patients. RESULTS: Using a stepwise multiple linear
      regression analysis, three predictors of serum immunoglobulin A level, ratio of
      aspartate aminotransferase to alanine aminotransferase, and platelet count were
      elicited, and a model for estimating cirrhosis was determined as follows: risk
      score = -0.113 + 0.0006056 x immunoglobulin A (mg/dL) + 0.155 x ratio of
      aspartate aminotransferase to alanine aminotransferase - 0.007079 x platelet
      (x10(4)/mm(3)). In the training sample, the sensitivity and specificity were 90%
      and 83%, respectively, when patients presenting a risk score >/=0.20 were
      estimated to be cirrhotic. When this model was applied to the validation sample,
      the sensitivity, specificity, positive predictive value, negative predictive
      value and accuracy were 83%, 97%, 83%, 97% and 94%, respectively. CONCLUSION: It
      is suggested that this model could be useful for the estimation of cirrhosis in
      patients with type 1 autoimmune hepatitis.

PMID- 18328064
TI  - Changes in intrahepatic gene expression profiles from chronic hepatitis to
      hepatocellular carcinoma in patients with hepatitis C virus infection.
AB  - AIM: DNA microarray technology has enabled genome-wide analysis of gene
      transcript levels, which has yielded insight into the molecular nature of
      hepatitis C virus infection. However, little insight into the molecular nature of
      the early to advanced stages of chronic liver disease has as yet been obtained.
      METHODS: We compared the gene expression profiles of liver biopsy specimens from
      14 patients at different stages of chronic hepatitis C. We also evaluated the
      liver tissue of hepatocellular carcinoma and its surrounding region obtained
      surgically in seven patients with hepatitis C virus infection. RESULTS: Of 21 073
      genes, 582 genes showed significant changes in expression levels across the
      disease group. Twenty-eight samples from six disease groups clustered according
      to the histological classification except for 4 samples. A heat map produced by
      hierarchical clustering revealed nine clusters where gene expression profiles
      were changed in abundance. Among 44 genes which changed twofold or more in
      transcript abundance, transcripts from chronic hepatitis tended to be
      upregulated, and gradually downregulated according to disease progression toward
      hepatocellular carcinoma in five of nine clusters. In chronic hepatitis,
      transcripts relating to metabolism and immune response were upregulated, while in
      hepatocellular carcinoma, transcripts associated with cell cycle, growth,
      proliferation, apoptosis and signaling pathway were upregulated. CONCLUSION:
      Disease progression in hepatitis C virus-infected patients appeared to be
      associated with changes in gene expression profiles in the liver consistent with
      plausible functional categories, although we should confirm these findings using
      larger samples.

PMID- 18328065
TI  - Common null variant, Arg192Stop, in a G-protein coupled receptor, olfactory
      receptor 1B1, associated with decreased serum cholinesterase activity.
AB  - AIM: Non-functioning single nucleotide polymorphisms (nSNPs) that result in
      premature termination codons, that is null-alleles of the respective genes, may
      have phenotypic effects on clinical parameters. We conducted association studies
      involving several G-protein coupled receptors (GPCRs) that harbor nSNPs, using
      clinical parameters of liver function in a general population consisting of 2969
      Japanese adults. METHODS: SNP typings were performed with TaqMan and Invader
      assays. Quantitative associations between genotypes and clinical parameters were
      analyzed by analysis of variance. Linkage disequilibrium (LD) was tested by
      Haploview Version 3.3. Haplotype-based association was performed using the
      haplo.stats program. RESULTS: A significant correlation (P = 0.0057) was
      identified between serum cholinesterase activity (CHE) and an nSNP (Arg192Stop)
      in the olfactory receptor (OR) 1B1 gene, a member of the GPCR gene family. This
      nSNP was associated with decreased serum CHE (P = 0.0013). LD analysis based on
      eight selected SNPs at the locus revealed three LD blocks. The Arg192Stop nSNP
      was located on the second LD block, which covered one-third of the 3'-portion of
      the gene. CONCLUSION: These results suggested that the null-allele of OR1B1 might
      affect metabolism of serum cholinesterase in carriers of this nSNP.

PMID- 18328066
TI  - Preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation in
      rats.
AB  - AIM: The aim of this study was to examine the preventive effects of ME3738 on
      hepatic fibrosis induced by bile duct ligation (BDL) in rats. METHODS: ME3738 (20
      mg/day) was administered orally for 21 days immediately after BDL. Fibrosis was
      assessed by measuring hepatic hydroxyproline (Hyp) content. Activated hepatic
      stellate cells (HSCs) were assessed by alpha-smooth muscle actin (alpha-SMA)
      immunostaining. Hepatic thiobarbituric acid-reactive substance (TBARS), 4-hydroxy
      2-nonenal (4-HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG) immunostaining were
      used to analyze oxidative stress. The gene expressions of collagen-I,
      transforming growth factor-beta1 (TGF-beta1), tissue inhibitor of
      metalloproteinases-1 (TIMP-1), interleukin-6 (IL-6) and heme oxygenase-1 (HO-1)
      in the liver were examined by real-time reverse transcriptase polymerase chain
      reaction (RT-PCR). RESULTS: Hepatic Hyp content and the area of hepatic fibrosis
      in BDL rats treated with ME3738 were reduced by 24% and 39% compared with non
      treated BDL rats (hepatic Hyp, 9.40 +/- 2.85 vs. 12.39 +/- 3.91 mg/liver; P =
      0.036; area of hepatic fibrosis, 13.1 +/- 3.8 vs. 21.5 +/- 10.9; P = 0.045).
      Furthermore, alpha-SMA-positive cells were significantly reduced by 40% (22.3 +/-
      14.8 vs. 37.6 +/- 14.2; P = 0.011), collagen-I mRNA by 83% (6.5 +/- 2.2 vs. 38.3
      +/- 9.1; P = 0.002), HO-1 mRNA by 58% (4.13 +/- 1.22 vs. 9.73 +/- 1.80; P =
      0.018) and hepatic HO-1 content by 26% (2.13 +/- 0.80 vs. 2.87 +/- 0.19; P =
      0.01) following ME3738 treatment. The hepatic expression of TBARS, 4-HNE, 8-OHdG
      and mRNA levels of TGF-beta1, TIMP-1 and IL-6 in the liver were unchanged by
      ME3738 treatment. CONCLUSION: Oral ME3738 administration may prevent the
      progression of hepatic fibrosis in BDL rats through suppression of the activation
      and collagen synthesis of HSC and, in part, oxidative stress. ME3738 has
      potential as a therapeutic drug for cholestatic liver fibrosis.

PMID- 18328067
TI  - Fulminant hepatitis and late onset hepatic failure in Japan.
AB  - AIM: A nationwide survey was performed to clarify the present state of fulminant
      hepatitis and late onset hepatic failure (LOHF) between 1998 and 2003 in Japan.
      METHODS: Three hundred and sixteen, 318 and 64 patients, respectively, with acute
      and subacute types of fulminant hepatitis and LOHF, in which grade II or more
      severe hepatic encephalopathy occurred within 10 days, between 11 days and 8
      weeks and between 8 and 24 weeks, respectively, after the onset of disease
      symptoms, were analyzed. RESULTS: Complications such as metabolic syndrome were
      underlying in 41.5% of patients with subacute fulminant hepatitis and 51.6% of
      patients with LOHF, and most of such patients had received daily medications. The
      etiology of fulminant hepatitis was viral infection in 71.2% of the acute type
      and 31.8% in the subacute type. Hepatitis B virus (HBV) infection was found in
      most of these patients; transient infection prevailed in the acute type; and HBV
      carrier prevailed in the subacute type. The etiology was unknown in 42.8% and
      53.1% of the subacute type and LOHF, respectively. Autoimmune hepatitis and drug
      allergy-induced liver injury were found in 10.7% and 11.3%, respectively, of the
      subacute type. Artificial liver support with plasma exchange and/or
      hemodiafiltration took place in more than 90% of all patients. The survival rates
      of the patients without liver transplantation were 53.7% in the acute and 24.4%
      in the subacute type, and 11.5% in LOHF. The prognosis was especially poor in HBV
      carriers and patients with autoimmune hepatitis. The survival rates of those who
      underwent liver transplantation were 56.3%, 39.3% and 23.4% in the acute type,
      subacute type and LOHF, respectively. CONCLUSION: The etiology and prognosis
      differed in patients with fulminant hepatitis and LOHF depending on the disease
      types in Japan, and liver transplantation improved the prognosis of the patients
      irrespective of the disease type and etiology.

PMID- 18328068
TI  - Role of mitogen-activated protein kinases in tauroursodeoxycholic acid-induced
      bile formation in cholestatic rat liver.
AB  - AIM: Ursodeoxycholic acid exerts anticholestatic effects in various cholestatic
      disorders and experimental models of cholestasis. Its taurine conjugate (TUDCA)
      stimulates bile salt secretion in isolated perfused rat livers (IPRL) under
      physiological, non-cholestatic conditions, in part by mitogen-activated protein
      kinase (MAPK)-dependent mechanisms. The role of MAPK in the anticholestatic
      effect of TUDCA, however, is unclear. Therefore, we studied the role of MAPK in
      the anticholestatic effect of TUDCA in IPRL and isolated rat hepatocytes (IRH) in
      taurolithocholic acid (TLCA)-induced cholestasis. METHODS: Bile flow, biliary
      levels of 2,4-dinitrophenyl-S-glutathione (GS-DNP) as a marker of hepatobiliary
      organic anion secretion and activity of lactate dehydrogenase (LDH) in
      hepatovenous effluate as a marker of hepatocellular damage in IPRL perfused with
      TUDCA and/or TLCA were determined in the presence or absence of MAPK inhibitors.
      In addition, phosphorylation of Erk 1/2 and p38(MAPK) induced by TUDCA and/or
      TLCA was studied by Western immunoblot in IPRL and IRH. RESULTS: TUDCA-induced
      bile flow was impaired by the Erk 1/2 inhibitor PD98059 in normal livers (-28%),
      but not in livers made cholestatic by TLCA. GS-DNP secretion was unaffected by
      PD98059 under both conditions. TUDCA-induced bile formation and organic anion
      secretion both in the presence and absence of TLCA were unaffected by the
      p38(MAPK) inhibitor SB202190. Erk 1/2 phosphorylation in liver tissue was
      unchanged after bile salt exposure for 70 min, but was transiently enhanced by
      TUDCA in IRH. CONCLUSION: MAPK do not mediate the anticholestatic effects of
      TUDCA in TLCA-induced cholestasis.

PMID- 18328069
TI  - HCV selection and HVR1 evolution in a chimpanzee chronically infected with HCV-1
      over 12 years.
AB  - AIM: To study hepatitis C virus (HCV) selection and hypervariable region-1 (HVR1)
      evolution in a chimpanzee chronically infected with HCV-1 over 12 years after
      inoculation with a human factor VIII concentrate contaminated with HCV. METHODS:
      From the inoculum, the earliest chimpanzee plasma and 12 annual plasma samples,
      HCV fragments including HVR1 were amplified followed by cloning and sequencing.
      RESULTS: Five HCV subtypes - 1a, 1b, 2a, 2b, 3a - and multiple 1a strains were
      identified in the inoculum. Two 1a strains were found in the earliest chimpanzee
      sample, while a single HCV-1 strain was detected in the 12 annual samples. None
      of the chimpanzee sequences were identical to those found in the inoculum. Over
      12 years, HVR1 patterns changed irregularly, but a few patterns showed identical
      nucleotide or amino acid sequences. In the last three years, the variety of HVR1
      patterns decreased, while the proportion of major patterns increased. These
      corresponded to a higher virus load and a lower number of amino acid
      substitutions. Simultaneously, the HVR1 sequences became more similar to the
      consensus sequence of the 1a subtype. CONCLUSION: HCV selection was observed from
      the inoculum to the inoculated chimpanzee and from the early acute hepatitis to
      the persistent chronic infection. The selection occurred at three levels: among
      subtypes after transmission, among isolates during acute hepatitis and among
      quasispecies in chronic infection.

PMID- 18328070
TI  - Suppressive effect of oral administration of branched-chain amino acid granules
      on oxidative stress and inflammation in HCV-positive patients with liver
      cirrhosis.
AB  - AIM: In chronic hepatitis C virus (HCV) infection, it is thought that both
      chronic persistent inflammation and oxidative stress contribute to the
      development of hepatocellular carcinoma (HCC), and it has been reported that long
      term oral supplementation with branched-chain amino acid (BCAA) granules could
      inhibit liver carcinogenesis. However, the extent of the involvement of these
      factors remains obscure. METHODS: To clarify the involvement of inflammation and
      oxidative stress in the inhibition of liver carcinogenesis, we evaluated the
      effect of oral administration of BCAA granules on oxidative stress and
      inflammation in HCV-positive patients with liver cirrhosis. RESULTS: Twenty-seven
      patients were enrolled in the study: 18 of the patients were treated with BCAA
      granules (administered group) and nine were observed without BCAA granules (non
      administered group). In the non-administered group, the production of oxidative
      stress, as indicated by urine 8-hydroxydeoxyguanosine (8-OHdG) and 15-F2t
      Isoprostane (8-IsoPs), significantly increased with time, while in the
      administered group the levels of ferritin and 8-OHdG decreased significantly.
      Comparison of the two groups demonstrated that highly sensitive CRP, ferritin, 8
      OHdG and 8-IsoPs were significantly reduced by taking BCAA granules. The time
      course analysis showed that ferritin and highly sensitive CRP seemed to decrease
      first, followed by a decrease of 8-OHdG and 8-IsoPs. CONCLUSION: These findings
      indicated that the administration of BCAA granules influenced microinflammation
      and the metabolism of iron in HCV-positive patients with liver cirrhosis, and
      subsequently seemed to reduce the production of oxidative stress, possibly
      leading to a decrease in the occurrence of HCC.

PMID- 18328071
TI  - Prevalence of esophagogastric varices in patients with non-alcoholic
      steatohepatitis.
AB  - AIM: In non-alcoholic steatohepatitis (NASH), fibrosis begins around the central
      veins, as also happens with alcoholic liver disease, so the symptoms of portal
      hypertension may be due to central vein occlusion. The aim of this study was to
      define the prevalence of esophagogastric varices and the clinical outcome after
      endoscopic treatment in NASH patients with severe fibrosis. METHODS: The subjects
      were 72 patients with clinicopathologically confirmed NASH who had bridging
      fibrosis (F3) or cirrhosis (F4) determined by the examination of liver biopsy
      specimens, and who underwent upper gastrointestinal endoscopy. The prevalence and
      pattern of endoscopically detected varices at the time of liver biopsy were
      evaluated. The results of NASH patients (n = 11) with endoscopically treated
      esophageal varices were compared to those with alcoholic (n = 67) and hepatitis C
      virus-associated cirrhosis (n = 152). RESULTS: Esophagogastric varices were
      detected in 34 out of the 72 (47.2%) patients; esophageal varices in 25 (34.7%)
      and gastric varices in nine (12.5%), while six of these patients had variceal
      bleeding. In NASH patients, the cumulative recurrence-free probability at 24
      months after endoscopic treatment was 63.6%, the bleeding-free probability was
      90.9%, and the 5-year survival was 100%. Only one out 11 patients died of liver
      failure at 70 months after treatment. CONCLUSION: About half of NASH patients
      with severe fibrosis had esophagogastric varices. The clinical status and course
      of the varices do not necessarily improve after endoscopic treatment. NASH
      patients with esophagogastric varices need to be followed up carefully, like
      patients with other chronic liver diseases.

PMID- 18328072
TI  - Sustained response to interferon-alpha plus ribavirin therapy for chronic
      hepatitis C is closely associated with increased dynamism of intrahepatic natural
      killer and natural killer T cells.
AB  - AIM: Previous studies have revealed that functional impairment of innate immune
      cells, including natural killer (NK) and natural killer T (NKT) cells, might be
      associated with the persistence of hepatitis C virus (HCV) infection. However,
      the involvement of innate immune cells, which predominate in the liver, in
      therapeutic HCV clearance is still unclear. METHODS: To clarify the role of
      intrahepatic innate immune cells in the clinical outcome of patients with chronic
      hepatitis C (CHC) treated with interferon-alpha plus ribavirin (IFN/RBV), we
      prospectively investigated the status of NK and NKT cells in paired liver biopsy
      and peripheral blood (PB) samples obtained from 21 CHC patients before and
      immediately after IFN/RBV treatment by flow cytometry. Normal liver and PB
      samples were obtained from 10 healthy donors for living donor liver
      transplantation. RESULTS: Before treatment, intrahepatic NK and NKT cells
      constituted a significantly lower proportion in CHC patients than in healthy
      individuals (P < 0.05). After IFN/RBV treatment, the proportions and absolute
      numbers of CD3(-)CD161(+) NK and CD3(+)CD56(+) NKT cells in the liver, but not in
      PB, were significantly increased in sustained responders (SR) as compared with
      poor responders (P < 0.05). The proportion of CD3(+)CD161(+) NKT cells was also
      increased in the liver of SR after the treatment. Moreover, there was a striking
      increase of activated CD152(+) cells among CD3(+)CD56(+) NKT cells in the liver
      of SR (P = 0.041). CONCLUSION: These findings demonstrate that sustained response
      to IFN/RBV treatment for patients with CHC is closely associated with increased
      dynamism of NK and NKT cells in the liver.

PMID- 18328073
TI  - Bond strength of denture teeth to acrylic resin: effect of thermocycling and
      polymerisation methods.
AB  - BACKGROUND: Failure of bonding between acrylic resin teeth and denture base
      material is a considerable problem for patients who wear complete dentures.
      OBJECTIVE: The purpose of this study was to evaluate the bond strength between
      acrylic resins and resin denture teeth with different thermocycling and
      polymerisation methods. MATERIALS AND METHODS: Microwave-polymerised (Onda-Cryl),
      heat-polymerised (Classico) and autopolymerising (Jet) acrylic resins and resin
      denture tooth (Biotone) were used. The acrylic resins were polymerised according
      to the following: (A) microwave - fast cycle, Onda-Cryl; (B) microwave - long
      cycle, Onda-Cryl; (C) microwave - manufacturer's cycle, Onda-Cryl; (T) water bath
      - long cycle, Classico; and (Q) bench polymerisation cycle, Jet. Twenty specimens
      were prepared for each polymerisation method. Ten were thermocycled, and 10 did
      not receive thermocycling. For the purpose of the study, a shear test was used.
      Data were analysed with the Kruskal-Wallis test and Dunn's multiple comparisons
      test (p = 0.05). RESULTS: Cycles B, C and T were similar (p > 0.05), and had
      statistically higher bonding values than cycles A and Q (p < 0.05) for the
      thermocycled and non-thermocycled groups. For all cycles, there were no
      statistically significant differences between thermocycled and non-thermocycled
      groups (p > 0.05), except for cycle Q (p = 0.0038). CONCLUSION: Thermocycling
      decreased the bond strength, but not significantly for microwave and heat
      polymerised cycles. Regarding the bond strength of denture teeth to acrylic
      resin, the fast microwave polymerisation cycle should be avoided when
      polymerising Onda-Cryl acrylic resin. In addition, Jet acrylic resin is not
      adequate for use in denture repair.

PMID- 18328074
TI  - Edentulous patients' knowledge of dental hygiene and care of prostheses.
AB  - OBJECTIVE: The aim of this study was to analyse denture users' oral care habits
      with regard to the use of their prostheses. BACKGROUND: Rehabilitative treatment
      is only successful when patients are motivated and aware of correct prosthesis
      use and hygiene. MATERIALS AND METHODS: Questionnaires were distributed to 150
      complete denture users at the Federal University of Bahia School of Dentistry,
      the Esmeralda Natividade Health Center, the Bahian Science Development Foundation
      and a Salvador nursing home. The questionnaire included information on gender,
      age, length of prosthesis use, cleaning methods and materials, etc. The data were
      analysed using EpiInfo version 6 software. The chi-squared test was used for
      statistical analysis, with a significance level of 5%. RESULTS: Questionnaire
      results showed that 78% of the subjects, with an average age of 67.3 years, had
      used the same complete denture for over 5 years. 64% slept with their prostheses
      and 44% removed them from the mouth only for cleaning. None of the patients
      interviewed knew anything about brushes designed specifically for complete
      dentures. 37.3% had a restricted diet and 44% believed that a complete denture
      would last for more than 10 years. CONCLUSION: Within the limitations of this
      study, it was concluded that the edentulous patients surveyed had limited
      awareness of prosthetic hygiene and long-term oral care despite extended periods
      of denture use.

PMID- 18328075
TI  - Toll-like receptor 4 signaling plays a role in triggering periodontal infection.
AB  - Toll-like receptors (TLRs) are a group of sensors on the surface of antigen
      presenting cells, such as dendritic cells and macrophages, which recognize
      microbial pathogens and induce innate and adaptive immune responses.
      Periodontitis is an inflammatory disease characterized by the destruction of
      tooth-supporting structures. In order to address whether TLR4 signaling plays a
      role in periodontitis, we studied the gene expression change in human periodontal
      ligament cells (HPDLCs) in response to TLR4 ligand, lipopolysaccharide treatment
      by microarray analysis. Expression of TLR4 was detected in HPDLCs.
      Lipopolysaccharide treatment increased the expression of 12 genes (more than
      twofold), including TLR4, TLR5, TLR7, Pellino 1, colony stimulating factor 2
      (CSF2) and IL-6. In addition, the expression of 15 genes (less than equal to
      twofold) was decreased, including Fos, LY64 and LY86. In addition, real-time PCR
      was used to confirm the change of gene expression of TLR4, IL-6 and Fos. We also
      showed that the upregulation of IL-6 by lipopolysaccharide treatment was TLR4
      dependent. This pattern of gene expression indicates that pathogens may trigger
      TLR4 signaling and cause periodontitis. Manipulating TLR4 signaling may
      potentially become one of the recognized therapies for periodontitis.

PMID- 18328076
TI  - Complete genomic characterization of an intertypic Sabin 3/Sabin 2 capsid
      recombinant.
AB  - The genetic properties of strain K/2002, isolated from fecal samples of a 7-month
      old child who had received his first oral poliovirus vaccine (OPV) dose at the
      age of 3 months, are described. Preliminary sequencing characterization of
      isolate K/2002 revealed an S3/S2 recombination event at the 3' end of the VP1
      coding region. A recombination event resulted in the introduction of six Sabin 2
      amino acid residues in a Sabin 3 genomic background. Furthermore, mutations
      associated with loss of the attenuated phenotype of Sabin 3 strains have been
      identified in the genome of isolate K/2002. The data presented here emphasize the
      need for careful planning of vaccination strategies, which involve stopping OPV
      administration in regions that are certified to be polio-free.

PMID- 18328077
TI  - Postnatal changes in the expression of genes for cryptdins 1-6 and the role of
      luminal bacteria in cryptdin gene expression in mouse small intestine.
AB  - Although there have been many fascinating studies on cryptdins, the information
      for each cryptdin isoform was not completely provided. In this study, the
      postnatal changes in the gene expression of cryptdin 1-6 were evaluated, and the
      patterns of change were compared between conventional and germ-free mice. Two
      patterns of postnatal change were observed: gene expression of cryptdins 1, 3 and
      6 increased gradually, and that of cryptdins 2 and 5 increased rapidly. Gene
      expression of cryptdin 4 increased gradually in the ileum but rapidly in the
      jejunum. Conventional mice showed significantly higher gene expression for all
      isoforms than germ-free mice. Interestingly, the difference in the gene
      expression for cryptdin 2, 4 and 5 between the jejunum and ileum seemed to be
      increased by the presence of the luminal bacteria. The results indicate that
      cryptdin isoforms develop differently depending on the isoform type, and that the
      gene expression of all cryptdin isoforms was affected by the presence of the
      luminal bacteria.

PMID- 18328078
TI  - The biosynthetic genes encoding for the production of the dynemicin enediyne core
      in Micromonospora chersina ATCC53710.
AB  - Dynemicin is a novel anthraquinone-fused member of the 10-membered enediyne
      antitumor antibiotic family. The development of a genetic system for the
      dynemicin producer Micromonospora chersina confirmed, for the first time, the
      requirement of the putative enediyne core biosynthetic genes (dynE8, U14 and U15)
      and a tailoring oxidase gene (orf23) for dynemicin production. Cloning and
      sequence analysis of a 76 kb of genomic sequence region containing dynE8 revealed
      a variety of genes conserved among known enediyne loci. Surprisingly, this
      fragment and flanking chromosomal DNA lacked any obvious genes encoding for the
      biosynthesis of the anthraquinone, suggesting that the location of genes encoding
      for the biosynthesis of the dynemicin enediyne core and the dynemicin
      anthraquinone are chromosomally distinct. The demonstrated trace production of a
      shunt product from mutant strain QGD23 (Deltaorf23) also sets the stage for
      subsequent studies to delineate the key steps in enediyne core biosynthesis and
      tailoring.

PMID- 18328079
TI  - Isolation and identification of equol-producing bacterial strains from cultures
      of pig faeces.
AB  - Transformation of daidzein to equol was compared during fermentation of three
      growth media inoculated with faeces from Erhualian piglets, but equol was
      produced from only one medium, M1. Two equol-producing strains (D1 and D2) were
      subsequently isolated using medium M1. Both strains were identified as
      Eubacterium sp., on the basis of morphological and physiological characteristics,
      and 16S rRNA gene sequence analysis showed that strains D1 and D2 were most
      closely related to previously characterized daidzein-metabolizing bacteria
      isolated from human faecal and rumen samples, respectively. This suggests that
      the ability to metabolize daidzein can be found among bacteria present within the
      mammalian intestine. The results provided the first account of conversion of
      daidzein directly to equol by bacterial species from farm animals. These strains
      may be of importance to the improvement of animal performance, and the use of
      medium M1 could provide a simple way to isolate bacterial strains capable of
      transforming daidzein into equol.

PMID- 18328080
TI  - Involvement of O8-antigen in altering beta-lactam antibiotic susceptibilities in
      Escherichia coli.
AB  - In spite of being dispensable, O-antigens are believed to facilitate various
      cellular processes and alter antibiotic sensitivities. Escherichia coli K-12
      (CS109) strains are lacking in O-antigens and are reported to be sensitive to
      antibiotics. To our surprise, E. coli 2443 (expressing O8-antigen) manifested two
      to fourfold higher sensitivities toward penicillin and its derivatives than
      strain CS109. However, sensitivities toward other structurally unrelated
      antibiotics remained unchanged. To understand the rationale behind such
      observations, we replaced the rfb locus of strain 2443 with that of E. coli K-12.
      The beta-lactam sensitivities of 2443 cells with replaced rfb locus appeared to
      be identical to those for CS109. Therefore, it is quite reasonable to hypothesize
      the possible involvement of O8-antigen in beta-lactam sensitization.

PMID- 18328081
TI  - Phylogenetic analysis of bacteria associated with Laminaria saccharina.
AB  - Bacterial communities associated with the brown alga Laminaria saccharina from
      the Baltic Sea and from the North Sea were investigated using denaturing gradient
      gel electrophoresis and 16S rRNA gene clone libraries. The rhizoid, cauloid,
      meristem and phyloid revealed different 16S rRNA gene denaturing gradient gel
      electrophoresis banding patterns indicating a specific association of bacterial
      communities with different parts of the alga. Associations with cauloid and
      meristem were more specific, while less specific associations were obtained from
      the old phyloid. In addition, seasonal and geographical differences in the
      associated communities were observed. Results from 16S rRNA gene libraries
      supported these findings. Bacterial phylotypes associated with the alga were
      affiliated with the Alphaproteobacteria (nine phylotypes), Gammaproteobacteria
      (nine phylotypes) and the Bacteroidetes group (four phylotypes). A number of
      bacteria associated with other algae and other marine macroorganisms were among
      the closest relatives of phylotypes associated with L. saccharina.

PMID- 18328083
TI  - Ecological role of volatiles produced by Epichloe: differences in antifungal
      toxicity.
AB  - Species of Epichloe (Ascomycota, Clavicipitaceae) are endophytic symbionts of
      pooid grasses. Sexual reproduction of the fungus depends on gamete-transferring
      Botanophila flies, which in earlier studies were shown to be specifically
      attracted by the fungal volatiles chokol K and methyl (Z)-3-methyldodec-2-enoate.
      As several Epichloe volatiles are known to have antimicrobial properties, it was
      hypothesised that the original function of insect-attracting volatiles is
      microbial deterrence. However, the origin of volatile compounds and their
      toxicity within an ecological context has not yet been clarified. We examined the
      inhibitory effect of chokol K and methyl (Z)-3-methyldodec-2-enoate on
      mycoparasites, plant pathogenic fungi and on Epichloe itself at ecologically
      relevant concentrations, and assessed volatile production in pure cultures of
      Epichloe on complex and defined media supplemented with inorganic sources of
      carbon and nitrogen. Chokol K reduced the spore germination of all tested fungi,
      whereas methyl (Z)-3-methyldodec-2-enoate had no inhibitory effect. Moreover,
      only chokol K was produced in culture, confirming its fungal origin. Our findings
      are consistent with the proposed scenario that fungal volatile substances have
      followed an evolutionary pathway from defence to attraction.

PMID- 18328084
TI  - Metagenomic analysis of a freshwater toxic cyanobacteria bloom.
AB  - High molecular weight (HMW) DNA prepared from a toxic freshwater cyanobacterial
      bloom sample was used to construct a PCR-generated 75-clone, 16S rRNA gene
      library and a 2850-clone bacterial artificial chromosome (BAC) library.
      Phylogenetic analysis of the 16S rRNA gene library demonstrated that members of
      eight phyla of domain Bacteria, which included Cyanobacteria, Actinobacteria,
      Verrucomicrobium, Bacteriodetes, Planctomycetes, Chloroflexi, Candidate Division
      OP10 and Alpha-, Beta- and Gammaproteobacteria, were present in the bloom
      community. Diversity estimates determined from 16S rRNA gene analysis and direct
      cell counts and morphological identification of phytoplanktons suggested that the
      bloom community was dominated by members of the genera Aphanizomenon and
      Cylindrospermopsis, phylum Cyanobacteria. BAC-end sequencing of 37 randomly
      selected clones and subsequent sequence analysis provided a snapshot of the total
      bloom community putative metabolic activities. The sequencing of the entire
      inserts of seven clones (clones designated 578, 67, 142, 543, 905, 1664 and 2089)
      selected from BAC-end sequence studies resulted in the generation of a total of
      144-kb sequence data and in the identification of 130 genes for putative proteins
      representing at least four phyla, Proteobacteria, Actinobacteria, Bacteroidetes
      and Cyanobacteria. This is the first report on a snapshot analysis of a limited
      metagenome of a toxic cyanobacterial freshwater bloom.

PMID- 18328082
TI  - Microbial community succession and bacterial diversity in soils during 77,000
      years of ecosystem development.
AB  - The origins of the biological complexity and the factors that regulate the
      development of community composition, diversity and richness in soil remain
      largely unknown. To gain a better understanding of how bacterial communities
      change during soil ecosystem development, their composition and diversity in
      soils that developed over c. 77 000 years of intermittent aeolian deposition were
      studied. 16S rRNA gene clone libraries and fatty acid methyl ester (FAME)
      analyses were used to assess the diversity and composition of the communities.
      The bacterial community composition changed with soil age, and the overall
      diversity, richness and evenness of the communities increased as the soil habitat
      matured. When analysed using a multivariate Bray-Curtis ordination technique, the
      distribution of ribotypes showed an orderly pattern of bacterial community
      development that was clearly associated with soil and ecosystem development.
      Similarly, changes in the composition of the FAMEs across the chronosequence were
      associated with biomarkers for fungi, actinomycetes and Gram-positive bacteria.
      The development of the soil ecosystem promoted the development of distinctive
      microbial communities that were reminiscent of successional processes often
      evoked to describe change during the development of plant communities in
      terrestrial ecosystems.

PMID- 18328085
TI  - C/EBPalpha identifies differentiating preadipocytes around hair follicles in
      foetal and neonatal rat and mouse skin.
AB  - Previous studies have described a close anatomical association between hair
      follicles and subcutaneous adipocytes, yet little is known about the
      developmental origin of this preadipocyte population. Many transcription factors
      controlling adipogenesis in cell culture have been described; however, the
      molecular events governing the process of adipogenesis in rodent skin in vivo are
      largely unknown. In this study, we investigated the onset and progression of
      adipocyte differentiation in the skin of foetal and newborn rats and mice. We
      first analysed the temporo-spatial expression pattern of the transcription factor
      C/EBPalpha, a key player in adipocyte differentiation. Oil red O staining was
      then used to identify the presence of lipid within mature adipocytes in the same
      skin samples. In both species, nuclear staining of C/EBPalpha was first seen in
      cells around and below the bases of fully formed hair follicles in foetal dermis
      between 2 and 3 days before birth. Over time, increasing numbers of cells became
      labelled with C/EBPalpha, predominantly located between, rather than below, the
      hair follicles. Oil red O staining followed exactly the same pattern seen with
      the C/EBPalpha antibody, but with a delay of 12-24 h, and histomorphometry showed
      that the C/EBPalpha labelled cells matured into lipid filled adipocytes. These
      data show that C/EBPalpha is a useful developmental marker of preadipocytes in
      vivo. The close developmental association and physical proximity between the
      lower follicle and surrounding preadipocytes leads us to postulate that follicles
      control local adipogenic events, via signalling or by contributing to the
      preadipocyte pool.

PMID- 18328086
TI  - Expression of NAD+ dependent 15-hydroxyprostaglandin dehydrogenase and protection
      of prostaglandins in human hair follicle.
AB  - NAD(+) dependent 15-hydroxyprostaglandin dehydrogenate (15-PGDH) catalyses
      oxidation of 15(S)-hydroxyl group of prostaglandins and as a result inactivates
      their physiological potential. Positive effects of prostaglandins or
      prostaglandin analogues were reported on terminal hair, vellus hair or eyelash
      growth and a complex prostaglandin network was recently described in human hair
      follicle. In the present study, we showed that 15-PGDH was expressed in human
      hair follicle mainly in melanocytes and keratinocytes, which brought us to
      consider this enzyme as a possible target to sustain local prostaglandin
      production. Using a recombinant enzymatic strategy, specific 15-PGDH inhibitors
      were screened. We identified a thiazolidine dione derivative exhibiting efficacy
      on follicular outer root sheath keratinocytes, since it concomitantly decreased
      the production of deactivated 13,14 dihydro 15-ketoprostaglandin F(2alpha) and
      sustained prostaglandin F(2alpha)in vitro production. In the context of recent
      interest in prostaglandins and prostaglandin analogues as hair regrowth agents,
      we postulated that the use of selected 15-PGDH inhibitors could reinforce or
      prolong the effect of these physiological mediators on hair and skin.

PMID- 18328087
TI  - Development of a non-invasive measurement system to the thickness of the
      subcutaneous adipose tissue layer.
AB  - BACKGROUND/PURPOSE: It is important to measure the thickness of hypodermis,
      including the subcutaneous fat layer in several fields such as global assessment
      of nutritional status and monitoring of dietary manipulation. It also provides
      useful information concerning the amount of peripheral adipose tissue and can be
      used as an index of obesity. METHODS: To measure the thickness of the
      subcutaneous adipose tissue layer, the optical properties of tissue components,
      several lipids and animal tissue samples in vitro were measured over the
      wavelength range from 1000 to 1700 nm, using the transmittance measurement system
      and the diffuse reflectance measurement system. A wavelength range for the
      thickness measurements was selected from the experimental result. The
      corresponding signal according to the changes of adipose tissue thickness was
      measured. RESULTS: Experimental data measured by the non-invasive measurement
      system were compared with the actual thickness of animal samples, and the results
      could be explained by the three-layered tissue model. The result showed high
      correlation to the thickness changes (R2 = 0.9954). CONCLUSIONS: The experimental
      result implies positive possibility for the development of a system to measure
      the thickness of subcutaneous adipose tissue using near infrared in vivo.

PMID- 18328088
TI  - Presence of epidermal allantoin further supports oxidative stress in vitiligo.
AB  - Xanthine dehydrogenase/xanthine oxidase (XDH/XO) catalyses the hydroxylation of
      hypoxanthine to xanthine and finally to uric acid in purine degradation. These
      reactions generate H(2)O(2) yielding allantoin from uric acid when reactive
      oxygen species accumulates. The presence of XO in the human epidermis has not
      been shown so far. As patients with vitiligo accumulate H(2)O(2) up to mm levels
      in their epidermis, it was tempting to examine whether this enzyme and
      consequently allantoin contribute to the oxidative stress theory in this disease.
      To address this question, reverse transcription-polymerase chain reaction,
      immunoreactivity, western blot, enzyme kinetics, computer modelling and high
      performance liquid chromatography/mass spectrometry analysis were carried out.
      Our results identified the presence of XDH/XO in epidermal keratinocytes and
      melanocytes. The enzyme is regulated by H(2)O(2) in a concentration-dependent
      manner, where concentrations of 10(-6 )m upregulates the activity. Moreover, we
      demonstrate the presence of epidermal allantoin in acute vitiligo, while this
      metabolite is absent in healthy controls. H(2)O(2)-mediated oxidation of Trp and
      Met in XO yields only subtle alterations in the enzyme active site, which is in
      agreement with the enzyme kinetics in the presence of 10(-3 )m H(2)O(2). Systemic
      XO activities are not affected. Taken together, our results provide evidence that
      epidermal XO contributes to H(2)O(2)-mediated oxidative stress in vitiligo via
      H(2)O(2)-production and allantoin formation in the epidermal compartment.

PMID- 18328089
TI  - Social correlates of cigarette smoking among Icelandic adolescents: a population
      based cross-sectional study.
AB  - BACKGROUND: Previous research has shown that between 80 and 90 percent of adult
      smokers report having started smoking before 18 years of age. Several studies
      have revealed that multiple social factors influence the likelihood of smoking
      during adolescence, the period during which the onset of smoking usually occurs.
      To better understand the social mechanisms that influence adolescent smoking, we
      analyzed the relationship and relative importance of a broad spectrum of social
      variables in adolescent smoking in Iceland, a Nordic country with high per-capita
      income. METHODS: We used cross-sectional data from 7,430 14- to 16 year-old
      students (approximately 81% of all Icelanders in these age cohorts) in the 2006
      Youth in Iceland study. The Youth in Iceland studies are designed to investigate
      the role of several cognitive, behavioral, and social factors in the lives of
      adolescents, and the data collected are used to inform the design,
      implementation, and evaluation of substance use prevention programs that are
      being developed by Icelandic social scientists, policy makers, and practitioners.
      RESULTS: Our analysis revealed that friends' smoking behavior and attitude toward
      smoking were strongly associated with adolescent smoking and other tobacco use,
      as well as alcohol consumption during the previous 30 days. Main protective
      factors were parent's perceived attitude toward smoking, the quantity of time
      spent with parents, absence of serious verbal conflict between parents and
      adolescents, and participation in physical activity. Family structure was related
      to adolescent smoking to a small extent, but other background factors were not.
      CONCLUSION: We conclude that multiple social factors are related to adolescent
      smoking. Parents and other primary preventive agents need to be informed about
      the complicated nature of the adolescent social world in order to maximize their
      impact.

PMID- 18328090
TI  - Long-term retention on treatment with lumiracoxib 100 mg once or twice daily
      compared with celecoxib 200 mg once daily: a randomised controlled trial in
      patients with osteoarthritis.
AB  - BACKGROUND: The efficacy, safety and tolerability of lumiracoxib, a novel
      selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated in previous
      studies of patients with osteoarthritis (OA). As it is important to establish the
      long-term safety and efficacy of treatments for a chronic disease such as OA, the
      present study compared the effects of lumiracoxib at doses of 100 mg once daily
      (o.d.) and 100 mg twice daily (b.i.d.) with those of celecoxib 200 mg o.d. on
      retention on treatment over 1 year. METHODS: In this 52-week, multicentre,
      randomised, double-blind, parallel-group study, male and female patients (aged at
      least 40 years) with symptomatic primary OA of the hip, knee, hand or spine were
      randomised (1:2:1) to lumiracoxib 100 mg o.d. (n = 755), lumiracoxib 100 mg
      b.i.d. (n = 1,519) or celecoxib 200 mg o.d. (n = 758). The primary objective of
      the study was to demonstrate non-inferiority of lumiracoxib at either dose
      compared with celecoxib 200 mg o.d. with respect to the 1-year retention on
      treatment rate. Secondary outcome variables included OA pain in the target joint,
      patient's and physician's global assessments of disease activity, Short Arthritis
      assessment Scale (SAS) total score, rescue medication use, and safety and
      tolerability. RESULTS: Retention rates at 1 year were similar for the lumiracoxib
      100 mg o.d., lumiracoxib 100 mg b.i.d. and celecoxib 200 mg o.d. groups (46.9% vs
      47.5% vs 45.3%, respectively). It was demonstrated that retention on treatment
      with lumiracoxib at either dose was non-inferior to celecoxib 200 mg o.d.
      Similarly, Kaplan-Meier curves for the probability of premature discontinuation
      from the study for any reason were similar across the treatment groups. All three
      treatments generally yielded comparable results for the secondary efficacy
      variables and all treatments were well tolerated. CONCLUSION: Long-term treatment
      with lumiracoxib 100 mg o.d., the recommended dose for OA, was as effective and
      well tolerated as celecoxib 200 mg o.d. in patients with OA. TRIAL REGISTRATION:
      clinicaltrials.gov NCT00145301.

PMID- 18328092
TI  - A variant form of acute reversible cardiomyopathy: a case report.
AB  - INTRODUCTION: Stress cardiomyopathy, also known as Takotsubo cardiomyopathy or
      left ventricular apical ballooning, has been linked to emotional or physical
      stress resulting in transient left ventricular dysfunction. It typically affects
      the mid and apical left ventricular segments. At onset, it resembles acute
      myocardial infarction, due to the acute onset of chest pain and ST-T segment
      elevation. However, there is minimal biomarker elevation and a normal coronary
      artery angiogram. CASE PRESENTATION: We report a case of a woman with transient
      myocardial injury after a stressful event, presenting with a variation of the
      affected segments. In this case, only the basal and mid portions of the left
      ventricle were affected, while the apex was completely spared. Coronary
      angiography revealed no significant occlusion and left ventricular function had
      recovered completely by the third day of hospitalization. CONCLUSION: We present
      a variant form of stress cardiomyopathy, affecting the basal and mid segments of
      the left ventricle.

PMID- 18328091
TI  - Exceptional molecular and coreceptor-requirement properties of molecular clones
      isolated from an Human Immunodeficiency Virus Type-1 subtype C infection.
AB  - BACKGROUND: The pathogenic significance of coreceptor switch in the viral
      infection of HIV-1 is not completely understood. This situation is more complex
      in subtype C infection where coreceptor switch is either absent or extremely
      rare. To gain insights into the mechanisms that underlie coreceptor requirement
      of subtype C, we screened several primary viral isolates and identified a
      clinical sample that demonstrated a potential to grow on standard T-cell lines
      with no detectable CCR5 expression. The subject was diagnosed with HIV-1
      associated dementia in the absence of opportunistic infections of the brain. To
      isolate molecular clones from this virus, we devised a novel strategy based on
      anchor primers that target a sequence in the reverse transcriptase, highly
      conserved among diverse subtypes of HIV-1. RESULTS: Using this strategy, we
      isolated 8 full-length molecular clones from the donor. Two of the eight
      molecular clones, 03In94_D17 and 03In94_D24, (D17 and D24) generated replication
      competent viruses. Phylogenetic analysis of the full-length viral sequences
      revealed that both clones were non-recombinant subtype C viruses. They contain
      intact open reading frames in all the viral proteins. Both the viral clones are
      endowed with several unique molecular and biological properties. The viral
      promoter of the clones is characterized by the presence of four NF-kB binding
      elements, a feature rarely seen in the subtype C HIV-1 LTR. Interestingly, we
      identified the coexistence of two different forms of Rev, a truncated form common
      to subtype C and a full-length form less common for this subtype, in both
      proviral and plasma virus compartments. An exceptional property of the viruses,
      atypical of subtype C, is their ability to use a wide range of coreceptors
      including CCR5, CXCR4, and several others tested. Sequence analysis of Env of D17
      and D24 clones identified differences within the variable loops providing
      important clues for the expanded coreceptor use. The V1, V2 and V4 loops in both
      of the molecular clones are longer due to the insertion of several amino acid
      residues that generated potential N-linked glycosylation sites. CONCLUSION: The
      exceptional biological and molecular properties of these clones make them
      invaluable tools to understand the unique pathogenic characteristics of subtype
      C.

PMID- 18328093
TI  - Felix Battistella, UC Davis Chief of Trauma and Emergency Surgery, Editorial
      Board member of World Journal of Emergency Surgery, dies at 48, January 22 2008.

PMID- 18328094
TI  - Improved determination of plasmid copy number using quantitative real-time PCR
      for monitoring fermentation processes.
AB  - BACKGROUND: Recombinant protein production in Escherichia coli cells is a complex
      process, where among other parameters, plasmid copy number, structural and
      segregational stability of plasmid have an important impact on the success of
      productivity. It was recognised that a method for accurate and rapid
      quantification of plasmid copy number is necessary for optimization and better
      understanding of this process. Lately, qPCR is becoming the method of choice for
      this purpose. In the presented work, an improved qPCR method adopted for PCN
      determination in various fermentation processes was developed. RESULTS: To avoid
      experimental errors arising from irreproducible DNA isolation, whole cells,
      treated by heating at 95 degrees C for 10 minutes prior to storage at -20 degrees
      C, were used as a template source. Relative quantification, taking into account
      different amplification efficiencies of amplicons for chromosome and plasmid, was
      used in the PCN calculation. The best reproducibility was achieved when the
      efficiency estimated for specific amplicon, obtained within one run, was
      averaged. It was demonstrated that the quantification range of 2 log units (100
      to 10000 bacteria per well) enable quantification in each time point during
      fermentation. The method was applied to study PCN variation in fermentation at 25
      degrees C and the correlation between PCN and protein accumulation was
      established. CONCLUSION: Using whole cells as a template source and relative
      quantification considering different PCR amplification efficiencies are
      significant improvements of the qPCR method for PCN determination. Due to the
      approaches used, the method is suitable for PCN determination in fermentation
      processes using various media and conditions.

PMID- 18328095
TI  - High school drinking mediates the relationship between parental monitoring and
      college drinking: a longitudinal analysis.
AB  - BACKGROUND: College drinking is a significant public health problem. Although
      parental monitoring and supervision reduces the risk for alcohol consumption
      among younger adolescents, few studies have investigated the impact of earlier
      parental monitoring on later college drinking. This study examined whether
      parental monitoring indirectly exerts a protective effect on college drinking by
      reducing high school alcohol consumption. METHODS: A longitudinal cohort of 1,253
      male and female students, ages 17 to 19, attending a large, public, mid-Atlantic
      university was studied at two time points. First, data on high school parental
      monitoring and alcohol consumption were gathered via questionnaire during the
      summer prior to college entry. Second, during the first year of college, past
      year alcohol consumption was measured via a personal interview. Multiple
      regression models tested the relationship between parental monitoring and past
      year alcohol use (i.e., number of drinks per drinking day). RESULTS: Holding
      constant demographics, SAT score, and religiosity, parental monitoring had a
      significant protective effect on both high school and college drinking level.
      However, the association between parental monitoring and college drinking level
      became non-significant once high school drinking level was held constant.
      CONCLUSION: While parental monitoring did not directly influence college alcohol
      consumption, evidence for mediation was observed, whereby parental monitoring had
      an indirect influence on college drinking through reductions in high school
      drinking. Initiatives that promote effective parenting might be an important
      strategy to curb high-risk drinking among older adolescents. More research is
      needed to understand the nature and degree of parent-child communication that is
      necessary to extend the protective influence of parents into the college years.

PMID- 18328096
TI  - Unusual presentation of basilar artery stroke secondary to patent foramen ovale:
      a case report.
AB  - INTRODUCTION: We report a case of a patient presenting with neuropsychiatric
      manifestations secondary to paradoxical embolism CASE PRESENTATION: Unexplained
      rapid onset of confusion with amnesia and minimal neurological deficits can be a
      manifestation of various systemic causes of which stroke, either ischemic or
      hemorrhagic, is one. Thorough and systematic evaluation of these patients can be
      highly rewarding in terms of optimizing patient outcome. We report the case of a
      45-year-old woman whose initial presentation was with acute onset of confusion,
      memory loss with personality change and headaches. A differential diagnosis of
      systemic illness and cerebral pathology was entertained. She was empirically
      treated for neurological infection. Brain imaging revealed bilateral thalamic and
      cerebellar infarction. Further evaluation with an aim to define the etiology,
      revealed the diagnosis of Patent Foramen Ovale with paradoxical embolism. The
      differential diagnosis of unexplained rapid onset of confusion, amnesia with
      minimal motor neurological deficits and relevant appropriate investigations are
      discussed in this case report. CONCLUSION: This case highlights the importance of
      recognising the atypical manifestations of posterior fossa stroke. In young
      patients presenting with non-focal neuropsychiatric manifestations, paradoxical
      embolism, secondary to patent foramen ovale is a possible cause.

PMID- 18328097
TI  - Correlates of HIV, HBV, HCV and syphilis infections among prison inmates and
      officers in Ghana: A national multicenter study.
AB  - BACKGROUND: Prisons are known to be high-risk environments for the spread of
      bloodborne and sexually transmitted infections. Prison officers are considered to
      have an intermittent exposure potential to bloodborne infectious diseases on the
      job, however there has been no studies on the prevalence of these infections in
      prison officers in Ghana. METHODS: A national multicenter cross-sectional study
      was undertaken on correlates of human immunodeficiency virus (HIV), hepatitis B
      virus (HBV), hepatitis C virus (HCV), and syphilis infections in sample of prison
      inmates and officers from eight of ten regional central prisons in Ghana. A total
      of 1366 inmates and 445 officers were enrolled between May 2004 and December
      2005. Subjects completed personal risk-factor questionnaire and provided blood
      specimens for unlinked anonymous testing for presence of antibodies to HIV, HCV
      and Treponema pallidum; and surface antigen of HBV (HBsAg). These data were
      analyzed using both univariate and multivariate techniques. RESULTS: Almost 18%
      (1336) of 7652 eligible inmates and 21% (445) of 2139 eligible officers in eight
      study prisons took part. Median ages of inmates and officers were 36.5 years
      (range 16-84) and 38.1 years (range 25-59), respectively. Among inmates, HIV
      seroprevalence was 5.9%, syphilis seroprevalence was 16.5%, and 25.5% had HBsAg.
      Among officers tested, HIV seroprevalence was 4.9%, HCV seroprevalence was 18.7%,
      syphilis seroprevalence was 7.9%, and 11.7% had HBsAg. Independent determinants
      for HIV, HBV and syphilis infections among inmates were age between 17-46, being
      unmarried, being illiterate, female gender, being incarcerated for longer than
      median time served of 36 months, history of homosexuality, history of intravenous
      drug use, history of sharing syringes and drug paraphernalia, history of
      participation in paid sexual activity, and history of sexually transmitted
      diseases. Independent determinants for HIV, HBV, HCV and syphilis infections
      among officers were age between 25-46, fale gender, being unmarried, being
      employed in prison service for longer than median duration of employment of 10
      years, and history of sexually transmitted diseases. CONCLUSION: The comparably
      higher prevalence of HIV, HBV, HCV and syphilis in prison inmates and officers in
      Ghana suggests probable occupational related transmission. The implementation of
      infection control practices and risk reduction programs targeted at prison
      inmates and officers in Ghana is urgently required to address this substantial
      exposure risk.

PMID- 18328098
TI  - Diversity of the parB and repA genes of the Burkholderia cepacia complex and
      their utility for rapid identification of Burkholderia cenocepacia.
AB  - BACKGROUND: Burkholderia cenocepacia is the most prominent species of the B.
      cepacia complex (Bcc), a group of nine closely related and difficult to identify
      bacteria that cause serious infections in patients with cystic fibrosis. Despite
      its clinical relevance, identification of B. cenocepacia as a single species is
      unavailable, as it splits by a widely used recA gene-based PCR identification
      method into discrete phylogenetic subgroups IIIA, IIIB, IIIC and IIID. With the
      aim of identifying gene targets suitable for unified detection of B. cenocepacia
      strains, we examined sequence polymorphisms in the repA and parB genes. These
      essential genes are involved in the replication and partitioning of bacterial
      replicons, hence we also had the opportunity for the first time to investigate
      the evolution of the multireplicon (three chromosome) structure of Bcc genomes.
      RESULTS: Alignment of the repA and parB genes from publicly available Bcc genome
      sequences enabled the design of primers for their amplification and sequence
      analysis. Multilocus sequencing typing, a highly discriminatory method for Bcc
      species and strain discrimination, was used to select strains of unique sequence
      types (STs) that spanned the known Bcc genetic diversity. Sequence datasets of
      repA (83 isolates, 67 STs) and parB (120 isolates, 95 STs) genes from the second
      chromosome were aligned and examined phylogenetically to identify polymorphisms
      suitable for identification of B. cenocepacia. In contrast to parB, the Bcc repA
      sequences demonstrated distinct clustering of B. cenocepacia from other species,
      which enabled the design a species-specific multiplex PCR. The novel single
      reaction B. cenocepacia detection method was tested on a panel of 142 different
      Bcc strains (142 STs) and distinguished recA groups IIIA, IIIB and IIID, from all
      other Bcc members with 100% sensitivity and 93% specificity. CONCLUSION: The repA
      based multiplex PCR is a useful aid to the rapid identification of the most
      clinically relevant B. cenocepacia recA subgroups IIIA, IIIB and IIID.
      Phylogenetic analysis of repA and parB genes demonstrated that acquisition of the
      second and third replicons of Bcc genomes occurred prior to their differentiation
      into discrete species and that the sharing of replicons across species had not
      occurred.

PMID- 18328099
TI  - Parasite-mediated disruptive selection in a natural Daphnia population.
AB  - BACKGROUND: A mismatch has emerged between models and data of host-parasite
      evolution. Theory readily predicts that parasites can promote host diversity
      through mechanisms such as disruptive selection. Yet, despite these predictions,
      empirical evidence for parasite-mediated increases in host diversity remains
      surprisingly scant. RESULTS: Here, we document parasite-mediated disruptive
      selection on a natural Daphnia population during a parasite epidemic. The mean
      susceptibility of clones collected from the population before and after the
      epidemic did not differ, but clonal variance and broad-sense heritability of post
      epidemic clones were significantly greater, indicating disruptive selection and
      rapid evolution. A maximum likelihood method that we developed for detecting
      selection on natural populations also suggests disruptive selection during the
      epidemic: the distribution of susceptibilities in the population shifted from
      unimodal prior to the epidemic to bimodal after the epidemic. Interestingly, this
      same bimodal distribution was retained after a generation of sexual reproduction.
      CONCLUSION: These results provide rare empirical support for parasite-driven
      increases in host genetic diversity, and suggest that this increase can occur
      rapidly.

PMID- 18328100
TI  - Iraq War mortality estimates: a systematic review.
AB  - BACKGROUND: In March 2003, the United States invaded Iraq. The subsequent number,
      rates, and causes of mortality in Iraq resulting from the war remain unclear,
      despite intense international attention. Understanding mortality estimates from
      modern warfare, where the majority of casualties are civilian, is of critical
      importance for public health and protection afforded under international
      humanitarian law. We aimed to review the studies, reports and counts on Iraqi
      deaths since the start of the war and assessed their methodological quality and
      results. METHODS: We performed a systematic search of 15 electronic databases
      from inception to January 2008. In addition, we conducted a non-structured search
      of 3 other databases, reviewed study reference lists and contacted subject matter
      experts. We included studies that provided estimates of Iraqi deaths based on
      primary research over a reported period of time since the invasion. We excluded
      studies that summarized mortality estimates and combined non-fatal injuries and
      also studies of specific sub-populations, e.g. under-5 mortality. We calculated
      crude and cause-specific mortality rates attributable to violence and average
      deaths per day for each study, where not already provided. RESULTS: Thirteen
      studies met the eligibility criteria. The studies used a wide range of
      methodologies, varying from sentinel-data collection to population-based surveys.
      Studies assessed as the highest quality, those using population-based methods,
      yielded the highest estimates. Average deaths per day ranged from 48 to 759. The
      cause-specific mortality rates attributable to violence ranged from 0.64 to 10.25
      per 1,000 per year. CONCLUSION: Our review indicates that, despite varying
      estimates, the mortality burden of the war and its sequelae on Iraq is large. The
      use of established epidemiological methods is rare. This review illustrates the
      pressing need to promote sound epidemiologic approaches to determining mortality
      estimates and to establish guidelines for policy-makers, the media and the public
      on how to interpret these estimates.

PMID- 18328101
TI  - Surgical site infections in Italian Hospitals: a prospective multicenter study.
AB  - BACKGROUND: Surgical site infections (SSI) remain a major clinical problem in
      terms of morbidity, mortality, and hospital costs. Nearly 60% of SSI diagnosis
      occur in the postdischarge period. However, literature provides little
      information on risk factors associated to in-hospital and postdischarge SSI
      occurrence. A national prospective multicenter study was conducted with the aim
      of assessing the incidence of both in-hospital and postdisharge SSI, and the
      associated risk factors. METHODS: In 2002, a one-month, prospective national
      multicenter surveillance study was conducted in General and Gynecological units
      of 48 Italian hospitals. Case ascertainment of SSI was carried out using
      standardized surveillance methodology. To assess potential risk factors for SSI
      we used a conditional logistic regression model. We also reported the odds ratios
      of in-hospital and postdischarge SSI. RESULTS: SSI occurred in 241 (5.2%) of
      4,665 patients, of which 148 (61.4%) during in-hospital, and 93 (38.6%) during
      postdischarge period. Of 93 postdischarge SSI, sixty-two (66.7%) and 31 (33.3%)
      were detected through telephone interview and questionnaire survey, respectively.
      Higher SSI incidence rates were observed in colon surgery (18.9%), gastric
      surgery (13.6%), and appendectomy (8.6%). If considering risk factors for SSI, at
      multivariate analysis we found that emergency interventions, NNIS risk score, pre
      operative hospital stay, and use of drains were significantly associated with SSI
      occurrence. Moreover, risk factors for total SSI were also associated to in
      hospital SSI. Additionally, only NNIS, pre-operative hospital stay, use of
      drains, and antibiotic prophylaxis were associated with postdischarge SSI.
      CONCLUSION: Our study provided information on risk factors for SSI in a large
      population in general surgery setting in Italy. Standardized postdischarge
      surveillance detected 38.6% of all SSI. We also compared risk factors for in
      hospital and postdischarge SSI, thus providing additional information to that of
      the current available literature. Finally, a large amount of postdischarge SSI
      were detected through telephone interview. The evaluation of the cost
      effectiveness of the telephone interview as a postdischarge surveillance method
      could be an issue for further research.

PMID- 18328102
TI  - Mild autonomic dysfunction in primary Sjogren's syndrome: a controlled study.
AB  - INTRODUCTION: The aim of this study was to compare cardiovascular autonomic
      nervous system function in patients with primary Sjogren's syndrome (pSS) with
      that in control individuals, and to correlate the findings with autonomic
      symptoms and the presence of exocrine secretory dysfunction. METHODS: Twenty
      seven female patients with pSS and 25 control individuals completed the COMPASS
      (Composite Autonomic Symptom Scale) self-reported autonomic symptom
      questionnaire. Beat-to-beat heart rate and blood pressure data in response to
      five standard cardiovascular reflex tests were digitally recorded using a
      noninvasive finger pressure cuff and heart rate variability was analyzed by
      Fourier spectral analysis. Analysis was performed by analysis of variance
      (ANOVA), multivariate ANOVA and repeated measures ANOVA, as indicated. Factor
      analysis was utilized to detect relationships between positive autonomic symptoms
      in pSS patients. RESULTS: Multiple, mild autonomic disturbances were observed in
      pSS patients relating to decreased heart rate variability, decreased blood
      pressure variability and increased heart rate, which were most evident in
      response to postural change. There was a strong trend toward an association
      between decreased heart rate variability and increased severity of the
      secretomotor, orthostatic, bladder, gastroparesis and constipation self-reported
      autonomic symptom cluster identified in pSS patients. This symptom cluster was
      also associated with fatigue and reduced unstimulated salivary flow, and
      therefore may be an important component of the clinical spectrum of this disease.
      CONCLUSION: There was evidence of mild autonomic dysfunction in pSS as measured
      with both cardiovascular reflex testing and self-reported symptoms. Pathogenic
      autoantibodies targeting M3 muscarinic receptors remain a strong candidate for
      the underlying pathophysiology, but practical assays for the detection of this
      autoantibody remain elusive.

PMID- 18328103
TI  - Large isoform of MRJ (DNAJB6) reduces malignant activity of breast cancer.
AB  - INTRODUCTION: Mammalian relative of DnaJ (MRJ [DNAJB6]), a novel member of the
      human DnaJ family, has two isoforms. The smaller isoform, MRJ(S), is studied
      mainly for its possible role in Huntington's disease. There are no reports of any
      biologic activity of the longer isoform, MRJ(L). We investigated whether this
      molecule plays any role in breast cancer. Our studies were prompted by
      interesting observations we made regarding the expression of MRJ in breast cancer
      cell lines and breast cancer tissue microarrays, as described below. METHODS:
      Expression of MRJ(L) from several breast cancer cell lines was evaluated using
      real-time PCR. Relative levels of the small and large isoforms in breast cancer
      cell lines were studied using Western blot analysis. A breast cancer progression
      tissue microarray was probed using anti-MRJ antibody. MRJ(L) was ectopically
      expressed in two breast cancer cell lines. These cell lines were evaluated for
      their in vitro correlates of tumor aggressiveness, such as invasion, migration,
      and anchorage independence. The cell lines were also evaluated for in vivo tumor
      growth and metastasis. The secreted proteome of the MRJ(L) expressors was
      analyzed to elucidate the biochemical changes brought about by re-expression of
      MRJ(L). RESULTS: We found that MRJ(L) is expressed at a significantly lower level
      in aggressive breast cancer cell lines compared with normal breast. Furthermore,
      in clinical cases of breast cancer expression of MRJ is lost as the grade of
      infiltrating ductal carcinoma advances. Importantly, MRJ staining is lost in
      those cases that also had lymph node metastasis. We report that MRJ(L) is a
      protein with a functional nuclear localization sequence. Expression of MRJ(L) via
      an exogenous promoter in breast cancer cell line MDA-MB-231 and in MDA-MB-435 (a
      cell line that metastasizes from the mammary fat pad) decreases their migration
      and invasion, reduces their motility, and significantly reduces orthotopic tumor
      growth in nude mice. Moreover, the secreted proteome of the MRJ(L)-expressing
      cells exhibited reduced levels of tumor progression and metastasis promoting
      secreted proteins, such as SPP1 (osteopontin), AZGP1 (zinc binding alpha2
      glycoprotein 1), SPARC (osteonectin), NPM1 (nucleophosmin) and VGF (VGF nerve
      growth factor inducible). On the other hand, levels of the secreted metastasis
      suppressor KiSS1 (melanoma metastasis suppressor) were increased in the secreted
      proteome of the MRJ(L)-expressing cells. We confirmed by quantitative RT-PCR
      analysis that the secreted profile reflected altered transcription of the
      respective genes. CONCLUSION: Collectively, our data indicate an important role
      for a totally uncharacterized isoform of DNAJB6 in breast cancer. We show that
      MRJ(L) is a nuclear protein that is lost in breast cancer, that regulates several
      key players in tumor formation and metastasis, and that is functionally able to
      retard tumor growth.

PMID- 18328104
TI  - Distinguishing post-treatment changes from recurrent disease in
      cholangiocarcinoma: a case report.
AB  - INTRODUCTION: Three-dimensional techniques for radiotherapy have expanded
      possibilities for partial volume liver radiotherapy. Characteristic, transient
      radiographic changes can occur in the absence of clinical radiation-induced liver
      disease after hepatic radiotherapy and must be distinguished from local
      recurrence. CASE PRESENTATION: In this report, we describe computed tomography
      changes after chemoradiotherapy for cholangiocarcinoma as an example of
      collaboration to determine the clinical significance of the radiographic finding.
      CONCLUSION: Because of improved three-dimensional, conformal radiotherapy
      techniques, consultation across disciplines may be necessary to interpret post
      treatment imaging findings.

PMID- 18328105
TI  - Breath acidification in adolescent runners exposed to atmospheric pollution: a
      prospective, repeated measures observational study.
AB  - BACKGROUND: Vigorous outdoors exercise during an episode of air pollution might
      cause airway inflammation. The purpose of this study was to examine the effects
      of vigorous outdoor exercise during peak smog season on breath pH, a biomarker of
      airway inflammation, in adolescent athletes. METHODS: We measured breath pH both
      pre- and post-exercise on ten days during peak smog season in 16 high school
      athletes engaged in daily long-distance running in a downwind suburb of Atlanta.
      The association of post-exercise breath pH with ambient ozone and particulate
      matter concentrations was tested with linear regression. RESULTS: We collected
      144 pre-exercise and 146 post-exercise breath samples from 16 runners (mean age
      14.9 years, 56% male). Median pre-exercise breath pH was 7.58 (interquartile
      range: 6.90 to 7.86) and did not change significantly after exercise. We observed
      no significant association between ambient ozone or particulate matter and post
      exercise breath pH. However both pre- and post-exercise breath pH were strikingly
      low in these athletes when compared to a control sample of 14 relatively
      sedentary healthy adults and to published values of breath pH in healthy
      subjects. CONCLUSION: Although we did not observe an acute effect of air
      pollution exposure during exercise on breath pH, breath pH was surprisingly low
      in this sample of otherwise healthy long-distance runners. We speculate that
      repetitive vigorous exercise may induce airway acidification.

PMID- 18328106
TI  - Merkel cell carcinoma of the upper extremity: case report and an update.
AB  - BACKGROUND: Merkel cell carcinoma is a rare but aggressive cutaneous primary
      small cell carcinoma. It is commonly seen in elderly affecting the head, neck,
      and extremities. Macroscopically may be difficult to distinguish MCC from other
      small cells neoplasms especially oat cell carcinoma of the lung. CASE
      PRESENTATION: It is presented a case report concerning a 72 years old male with a
      MMC on the dorsal aspect of the right wrist. The patient underwent a diagnostic
      excisional biopsy and after the histological confirmation of the diagnosis a
      second excision was performed to achieve free margins. No postoperative radiation
      or adjuvant chemotherapy was given and within 9 years follow up no recurrence was
      reported. CONCLUSION: Although most cases present as localized disease treatment
      should be definitive due to high rates of local or systemic recurrence. Treatment
      includes excision of the lesion, lymphadenectomy, postoperative radiotherapy and
      chemotherapy depending on the stage of the disease. Even when locoregional
      control is achieved close surveillance is required due to high rates of relapse.

PMID- 18328107
TI  - Single mitochondrial gene barcodes reliably identify sister-species in diverse
      clades of birds.
AB  - BACKGROUND: DNA barcoding of life using a standardized COI sequence was proposed
      as a species identification system, and as a method for detecting putative new
      species. Previous tests in birds showed that individuals can be correctly
      assigned to species in ~94% of the cases and suggested a threshold of 10x mean
      intraspecific difference to detect potential new species. However, these tests
      were criticized because they were based on a single maternally inherited gene
      rather than multiple nuclear genes, did not compare phylogenetically identified
      sister species, and thus likely overestimated the efficacy of DNA barcodes in
      identifying species. RESULTS: To test the efficacy of DNA barcodes we compared
      ~650 bp of COI in 60 sister-species pairs identified in multigene phylogenies
      from 10 orders of birds. In all pairs, individuals of each species were
      monophyletic in a neighbor-joining (NJ) tree, and each species possessed fixed
      mutational differences distinguishing them from their sister species.
      Consequently, individuals were correctly assigned to species using a statistical
      coalescent framework. A coalescent test of taxonomic distinctiveness based on
      chance occurrence of reciprocal monophyly in two lineages was verified in known
      sister species, and used to identify recently separated lineages that represent
      putative species. This approach avoids the use of a universal distance cutoff
      which is invalidated by variation in times to common ancestry of sister species
      and in rates of evolution. CONCLUSION: Closely related sister species of birds
      can be identified reliably by barcodes of fixed diagnostic substitutions in COI
      sequences, verifying coalescent-based statistical tests of reciprocal monophyly
      for taxonomic distinctiveness. Contrary to recent criticisms, a single DNA
      barcode is a rapid way to discover monophyletic lineages within a metapopulation
      that might represent undiscovered cryptic species, as envisaged in the unified
      species concept. This identifies a smaller set of lineages that can also be
      tested independently for species status with multiple nuclear gene approaches and
      other phenotypic characters.

PMID- 18328108
TI  - From inclusion to independence--training consumers to review research.
AB  - Health and medical research invariably impacts on the lives of everyday people.
      Organisations in the developed world are increasingly involving the public in
      health research projects, and research governance structures and processes. The
      form the involvement takes varies, as does the level of involvement, from
      individuals, to groups, to the wider community. Lay community members can be
      trained to independently review health and medical research, and wider societal
      involvement in funding decisions, can be effectively fostered. The theoretical
      foundation, design and development of a task based consumer-training program,
      including a number of enabling factors to support the success of such training
      are presented. This work is likely to be of value to those planning to train
      consumers in technical or complex areas.

PMID- 18328109
TI  - Pybel: a Python wrapper for the OpenBabel cheminformatics toolkit.
AB  - BACKGROUND: Scripting languages such as Python are ideally suited to common
      programming tasks in cheminformatics such as data analysis and parsing
      information from files. However, for reasons of efficiency, cheminformatics
      toolkits such as the OpenBabel toolkit are often implemented in compiled
      languages such as C++. We describe Pybel, a Python module that provides access to
      the OpenBabel toolkit. RESULTS: Pybel wraps the direct toolkit bindings to
      simplify common tasks such as reading and writing molecular files and calculating
      fingerprints. Extensive use is made of Python iterators to simplify loops such as
      that over all the molecules in a file. A Pybel Molecule can be easily
      interconverted to an OpenBabel OBMol to access those methods or attributes not
      wrapped by Pybel. CONCLUSION: Pybel allows cheminformaticians to rapidly develop
      Python scripts that manipulate chemical information. It is open source, available
      cross-platform, and offers the power of the OpenBabel toolkit to Python
      programmers.

PMID- 18328110
TI  - Metabolic profiling reveals therapeutic effects of Herba Cistanches in an animal
      model of hydrocortisone-induced 'kidney-deficiency syndrome'.
AB  - BACKGROUND: Herba Cistanches (Roucongrong) is effective in treating Shenxu Zheng
      ('kidney-deficiency syndrome'). However, the mechanisms and systemic metabolic
      responses to the herbal intervention are unclear. METHODS: Using GC-MS-based
      metabolic profiling, we investigated the metabolic responses to Herba Cistanches
      intervention in a rat model of the hydrocortisone-induced 'kidney-deficiency
      syndrome'. RESULTS: The metabolic profiles of the rats after hydrocortisone
      injection deviated from the pre-dose metabolic state at different time points,
      ranging from day 1 to day 10, whereas the metabolic profiles of the rats treated
      with both hydrocortisone and water extract of Herba Cistanches returned to the
      pre-dose state on day 10. CONCLUSION: The intervention of Herba Cistanches caused
      a systemic recovery from the hydrocortisone-induced metabolic perturbation in
      rats. This study also demonstrates that metabolic profiling is useful in studying
      therapeutic mechanisms of herbal medicines.

PMID- 18328111
TI  - No miRNA were found in Plasmodium and the ones identified in erythrocytes could
      not be correlated with infection.
AB  - BACKGROUND: The transcriptional regulation of Plasmodium during its complex life
      cycle requires sequential activation and/or repression of different genetic
      programmes. MicroRNAs (miRNAs) are a highly conserved class of non-coding RNAs
      that are important in regulating diverse cellular functions by sequence-specific
      inhibition of gene expression. What is know about double-stranded RNA-mediated
      gene silencing (RNAi) and posttranscriptional gene silencing (PTGS) in Plasmodium
      parasites entice us to speculate whether miRNAs can also function in Plasmodium
      infected RBCs. RESULTS: Of 132 small RNA sequences, no Plasmodium-specific miRNAs
      have been found. However, a human miRNA, miR-451, was highly expressed,
      comprising approximately one third of the total identified miRNAs. Further
      analysis of miR-451 expression and malaria infection showed no association
      between the accumulation of miR-451 in Plasmodium falciparum-iRBCs, the life
      cycle stage of P. falciparum in the erythrocyte, or of P. berghei in mice.
      Moreover, treatment with an antisense oligonucleotide to miR-451 had no
      significant effect on the growth of the erythrocytic-stage P. falciparum.
      METHODS: Short RNAs from a mixed-stage of P. falciparum-iRBC were separated in a
      denaturing polyacrylamide gel and cloned into T vectors to create a cDNA library.
      Individual clones were then sequenced and further analysed by bioinformatics
      prediction to discover probable miRNAs in P. falciparum-iRBC. The association
      between miR-451 expression and the parasite were analysed by Northern blotting
      and antisense oligonucleotide (ASO) of miR-451. CONCLUSION: These results
      contribute to eliminate the probability of miRNAs in P. falciparum. The absence
      of miRNA in P. falciparum could be correlated with absence of argonaute/dicer
      genes. In addition, the miR-451 accumulation in Plasmodium-infected RBCs is
      independent of parasite infection. Its accumulation might be only the residual of
      erythroid differentiation or a component to maintain the normal function of
      mature RBCs.

PMID- 18328112
TI  - The right to be wrong.

PMID- 18328113
TI  - Visceral helminths of wild boars (Sus scrofa leucomystax) in Japan, with special
      reference to a new species of the genus Morgascaridia Inglis, 1958 (Nematoda:
      Schneidernematidae).
AB  - Twenty-nine Japanese wild boars (Sus scrofa leucomystax), collected during the
      hunting seasons of 2005 and 2006 in the western part of the mainland of Japan
      (Honshu), were examined for their visceral helminths. Eighteen helminth parasites
      were prevalent in them, including 17 Nematoda species (Metastrongylus elongatus,
      Metastrongylus salmi, Metastrongylus asymmetricus, Metastrongylus pudendotechus,
      Stephanurus dentatus, Gnathostoma doloresi, Physocephalus sexulata, Ascarops
      strongylina, Capillaria suis, Ascaris suum, Globocephalus samoensis,
      Globocephalus longimucronatus, Strongyloides ransomi, Trichuris suis, Bourgelatia
      diducta, Oesophagostomum dentatum, and Oesophagostomum watanabei), and one
      Cestoda species (Pseudanoplocephala nipponensis). Muscle digestion of the
      diaphragm (using an artificial gastric juice) of 24 wild boars detected a single
      diplostomulum of probably Pharyngostomum cordatum. In addition, four female and
      six male adults of Morgascaridia kugii sp. n. (Nematoda: Schneidernematidae) were
      recovered from the large intestine of a single wild boar. Examination of an
      additional 20 samples of the stomach and 27 samples of the large intestine could
      not find this species. To date, recorded species of the genus Morgascaridia are
      limited to M. sellsi collected from wild boars in Uganda and Congo several
      decades ago, and thence, no records of the recovery are available. Morgascaridia
      kugii sp. n. differed from M. sellsi by smaller body dimensions, shorter distance
      between the precloacal sucker and the cloaca, smaller sizes of the copulatory
      spicules and the gubernaculum, and smaller sizes of uterine eggs.

PMID- 18328114
TI  - Paramphistomum daubneyi: production dynamics and infectivity of metacercariae
      originating from snails dissected at regular intervals.
AB  - Experimental infections of Galba truncatula with Paramphistomum daubneyi were
      carried out at 24 degrees C to study the dynamics of larval development in snails
      dissected at regular intervals and to determine if metacercarial production might
      be improved. When the shell height of snails (4, 5, 6 or 7 mm) at exposure
      increased (experiment A), the total number of metacercariae was significantly
      higher in the 6- and 7-mm snails than in the other two groups, and the
      differentiation period was shortened (the first cercariae encysted at day 35 post
      exposure (p.e.) instead of day 40 in the 4- and 5-mm groups). When the number of
      miracidia (two, three or five) for each 6-mm high G. truncatula increased
      (experiment B), a significant decrease of snail survival at day 30 p.e., a
      significant augmentation of prevalence, and a significant increase of
      metacercarial production were noted. In the two- and three-miracidium groups, the
      number of metacercariae was close to that found in the 6-mm snails from
      experiment 1, whereas they showed slower growth from day 45 to day 65 in the five
      miracidium group. In the two groups of lambs infected with metacercariae encysted
      at days 45 or 60 p.e., no difference in the numbers of adult worms was noted. In
      contrast, in the case of 35-day encysted larvae, the number of adult worms was
      clearly lower. Snail dissection allowed higher metacercarial production, a saving
      of 12-15 days at 24 degrees C to obtain these larvae, and a substantial decrease
      of their cost price for commercial production.

PMID- 18328115
TI  - Formulation of a strategy for the application of Duddingtonia flagrans to control
      caprine parasitic gastroenteritis.
AB  - Experiments on the influence of egg density and varying quantities of
      chlamydospores on the nematode-trapping ability of Duddingtonia flagrans,
      influence of D. flagrans on the larval translation of gastrointestinal nematodes,
      doses of chlamydospores required for the effective control of gastrointestinal
      nematodosis and the epidemiology of nematode parasites were conducted in goats,
      which generated baseline data required for strategic application of the
      biocontrol agent. The nematode-trapping ability of D. flagrans, measured by
      numerical enumeration of infective third-stage larvae developed in the faecal
      culture, revealed that the efficacy is dependent on both nematode egg and
      chlamydospore density. Pasture plot studies revealed that D. flagrans, if
      deposited at the same time as nematode eggs, prevents translation of third-stage
      larvae of caprine nematodes from the faecal pats onto the grass blades. Feeding
      of 1 x 106 chlamydospores per kg body weight and above to goats virtually
      eliminated larvae from the pasture. Application of as few as 1 x 104 and 1 x 105
      chlamydospores per kg body weight had a profound impact on larval recovery. The
      effect persisted as long as the chlamydospores were fed. Monthly faecal worm egg
      counts of adult goats maintained under a semi-intensive management system on the
      Chhattisgarh plain and pasture larval burden revealed that June to August were
      the months of high risk for nematodosis. Haemonchus was the dominant species
      recorded throughout the year. The present data can best be utilized by
      formulating a strategic control measure when the larval challenge to the animal
      is maximum (June to August), so as to prevent establishment of patent infection.
      The observations reinforced the strategy to be adopted for nematode parasite
      control in goats by applying the biocontrol option at the onset of the monsoon.

PMID- 18328116
TI  - How will public and animal health interventions drive life-history evolution in
      parasitic nematodes?
AB  - Infection caused by parasitic nematodes of humans and livestock can have
      significant health and economic costs. Treatments aimed at alleviating these
      costs, such as chemotherapy and vaccination, alter parasite survival and
      reproduction, the main selective pressures shaping life-history traits such as
      age to maturity, size and fecundity. Most authors have argued that the life
      history evolution prompted by animal and public health programmes would be
      clinically beneficial, generating smaller, less fecund worms, and several
      mathematical models support this view. However, using mathematical models of long
      lasting interventions, such as vaccination, and regularly repeated short
      interventions, such as drenching, we show here that the expected outcome actually
      depends on how mortality rates vary as a function of worm size and developmental
      status. Interventions which change mortality functions can exert selection
      pressure to either shorten or extend the time to maturity, and thus increase or
      decrease worm fecundity and size. The evolutionary trajectory depends critically
      on the details of the mortality functions with and without the intervention.
      Earlier optimism that health interventions would always prompt the evolution of
      smaller, less fecund and hence clinically less damaging worms is premature.

PMID- 18328117
TI  - Cross-sectional relationship between dietary carbohydrate, glycaemic index,
      glycaemic load and risk of the metabolic syndrome in a Korean population.
AB  - Little is known about the effect of dietary carbohydrate, glycaemic index (GI)
      and glycaemic load (GL) on the risk of the metabolic syndrome, especially in
      populations with white rice as the staple food. The study examined the cross
      sectional relationship between carbohydrate, GI, GL and risk of the metabolic
      syndrome. There were a total of 910 middle-aged Korean adults. Dietary
      carbohydrate, GI and GL were determined by an interview-administered FFQ. The
      metabolic syndrome was defined using the modified criteria published in the Third
      Report of the National Cholesterol Education Program Adult Treatment Panel III.
      The risk of developing the metabolic syndrome was positively related to dietary
      carbohydrate (P for trend = 0.03), GI (P for trend = 0.03) and GL intakes (P for
      trend = 0.02) in women after adjusting for potential confounding variables. Among
      the components of developing the metabolic syndrome, the risk of high TAG and low
      HDL-cholesterol were positively related to high GI and GL intakes in women. The
      risk of developing the metabolic syndrome was considerably higher in the highest
      quintiles of carbohydrate (OR 6.44; 95 % CI 2.16, 19.2), GI (OR 10.4; 95 % CI
      3.24, 33.3) and GL intakes (OR 6.68; 95 % CI 2.30, 19.4) than in the lowest
      quintiles among women with a BMI >/= 25 kg/m2. However, there was no difference
      in risk across quintiles of carbohydrate, GI and GL among women with a BMI < 25
      kg/m2. In conclusion, both the quantity and quality of carbohydrate intake has a
      positive relationship with the risk of the metabolic syndrome in women but this
      relationship was dependent on the BMI level.

PMID- 18328118
TI  - The association of darbepoetin alfa with hemoglobin and health-related quality of
      life in patients with chronic kidney disease not receiving dialysis.
AB  - OBJECTIVE: Anemia of chronic kidney disease (CKD) decreases patients' health
      related quality of life (HRQoL). The objective of this subanalysis was to
      determine the effect of every-other-week (Q2W) darbepoetin alfa on hemoglobin
      (Hb) levels and HRQoL measures in subjects with CKD who are naive to
      erythropoiesis-stimulating agents (ESAs). METHODS: STAAR was a 52-week,
      multicenter, single-arm study. Subject inclusion criteria included: > or = 18
      years of age and creatinine clearance < or = 70 mL/min or estimated glomerular
      filtration rate < or = 60 mL/min/1.73 m(2) but not receiving dialysis. Subjects
      included in this subanalysis were previously naive to ESAs, had Hb < 11 g/dL,
      were initiated on subcutaneous Q2W darbepoetin alfa to achieve a Hb level not to
      exceed 12 g/dL, and had responses to at least one question on the KDQOL-CRI forms
      administered at baseline, week 12, and week 52. RESULTS: Of 911 ESA-naive
      subjects enrolled in the study, 277 (30.4%) were included in this subanalysis.
      The majority of subanalysis subjects were Caucasian (63.2%) and/or women (54.5%).
      Mean Hb concentrations and all KDQOL-CRI scores improved significantly between
      baseline and week 12 (p < 0.0001), and were maintained until week 52. Darbepoetin
      alfa was well tolerated. CONCLUSIONS: Darbepoetin alfa initiated Q2W achieved and
      maintained Hb targets, and significantly improved and maintained HRQoL in study
      subjects with CKD. Limitations of the study must be considered when extrapolating
      these results to assess the benefits of treatment on HRQoL in the general CKD
      population.

PMID- 18328119
TI  - Prevalence of probable overactive bladder in a private obstetrics and gynecology
      group practice.
AB  - OBJECTIVE: To examine the prevalence of probable overactive bladder (OAB) in
      black, Hispanic, and white women. RESEARCH DESIGN AND METHODS: This was a cross
      sectional survey of women (aged > or = 18 years) presenting to a private
      obstetrics and gynecology group practice. The survey consisted of the Overactive
      Bladder-Validated 8 (OAB-V8) and other questions related to ethnicity, health
      history, desire for treatment, and reason for visit. MAIN OUTCOME MEASURE: The
      OAB-V8 is a validated, eight-item, self-administered questionnaire that assesses
      the degree of bother associated with OAB symptoms. Subjects scoring > or = 8 on
      the OAB-V8 were considered to have probable OAB. RESULTS: A total of 947 women
      completed the OAB-V8: 82% were black, 10% were white, and 4% were Hispanic. The
      prevalence of probable OAB was similar among different races/ethnicities, with
      35% of black, 36% of Hispanic, and 30% of white women scoring > or = 8 on the OAB
      V8. Micturition frequency, nocturia, and waking up at night were the most
      bothersome symptoms. History of constipation, history of urinary tract infection,
      and number of pregnancies were independent risk factors for probable OAB. Thirty
      five percent of patients with probable OAB and 5% of those without OAB desired
      information about OAB treatment options; however, only 5% of patients reported
      visiting their doctor for reasons related to their bladder symptoms. CONCLUSIONS:
      OAB is prevalent among black, white, and Hispanic women. Using a simple OAB
      awareness tool, such as the OAB-V8, can help clinicians identify patients with
      bothersome OAB symptoms who could benefit from treatment. The survey results may
      have been limited by incorrect self-reported responses, the demographics of the
      population, and incomplete surveys.

PMID- 18328120
TI  - A double-blind, randomized study evaluating losartan potassium monotherapy or in
      combination with hydrochlorothiazide versus placebo in obese patients with
      hypertension.
AB  - OBJECTIVES: The objective of this study was to evaluate the effects of losartan
      +/- hydrochlorothiazide (HCTZ) versus placebo in obese patients with systolic and
      diastolic hypertension. RESEARCH DESIGN AND METHODS: Randomized patients (n =
      261) were non-diabetic with systolic blood pressure (SBP) > or = 140 and < or =
      180 mmHg and diastolic BP (DBP) > or = 95 and < or = 115 mmHg, body mass index >
      30 kg/m(2), and waist circumference > 40 (males)/> 35 (females) inches. Patients
      were randomized to placebo or a forced titration of losartan 50 mg titrated at 4
      week intervals to losartan 100 mg, losartan 100 mg/HCTZ 12.5 mg, and losartan 100
      mg/HCTZ 25 mg. Primary efficacy measurements were change from baseline in SBP and
      DBP at 12 weeks. Secondary measurements were change from baseline in BPs at 8 and
      16 weeks, percent responders at 12 and 16 weeks, and safety/tolerability. Post
      hoc analyses were BP at 4 weeks and achievement of controlled BP (SBP < 140
      and/or DBP < 90 mmHg) at 12 and 16 weeks. RESULTS: Losartan 50 mg reduced BP from
      151.6/99.2 mmHg at baseline to 140.1/89.8 mmHg at week 4 (post hoc), 139.5/89.6
      mmHg with losartan 100 mg at week 8 (secondary), 134.3/85.9 mmHg with losartan
      100 mg/HCTZ 12.5 mg at week 12 (primary), and 132.1/84.9 mmHg with losartan 100
      mg/HCTZ 50 mg at week 16 (secondary) (all p < 0.05). Rates of clinical adverse
      experiences were similar between treatment groups. A limitation of these analyses
      is the relatively rapid rate of study drug titration, which may not have allowed
      for the evaluation of the full treatment effect at each titration step.
      CONCLUSIONS: We conclude that losartan alone or in combination with HCTZ was
      generally well tolerated and effective in the treatment of elevated systolic and
      diastolic BP in obese patients with hypertension.

PMID- 18328121
TI  - [Lay emphasis on shock, understand shock].

PMID- 18328122
TI  - [Guidelines for resuscitation of hypovolemic shock (2007)].
AB  - Hypovolemic shock is a pathophysiologic condition produced by rapid and
      significant loss of intravascular volume, leading sequentially to hemodynamic
      instability, decreases in oxygen delivery, decreased tissue perfusion, cellular
      hypoxia, cellular and organ damage, multiple organ dysfunction syndrome(MODS) and
      may end in death. Early recognition of hypovolemic shock and prompt systematic
      intervention will help avoid poor outcomes. The guideline is aimed to review the
      clinical aspects of hypovolemic shock (including definition, pathophysiology,
      monitoring, diagnosis, therapy, endpoints of resuscitation, et al.) and provide
      recommendations according to evidence.

PMID- 18328123
TI  - [Effect of arginine vasopressin on vascular reactivity and calcium sensitivity of
      vascular smooth muscle and its relationship to protein kinase C following
      hemorrhagic shock in rats].
AB  - OBJECTIVE: To investigate the effect of arginine vasopressin (AVP) on vascular
      reactivity and calcium sensitivity following hemorrhagic shock and their
      relationship to protein kinase C (PKC) isoforms. METHODS: With endothelium
      denuded superior mesenteric artery (SMA) rings procured from rats in hemorrhagic
      shock, the effects of AVP (5x10(-11), 5x10(-10) and 5x10(-9) mol/L) on
      contractile responses to norepinephrine (NE) and calcium sensitivity of SMA from
      hemorrhagic shock in rats and their relationship to alpha and Delta isoforms of
      PKC with isolated organ perfusion system were observed. RESULTS: AVP (5x10(-11),
      5x10(-10) and 5x10(-9) mol/L) markedly restored the vascular reactivity and
      calcium sensitivity following hemorrhagic shock, converting the cumulative
      concentration-response curve of NE and Ca2+ shift to the left, and its maximum
      concentration force (Emax) was significantly increased (all P<0.01) in a
      concentration dependent manner. Significant statistical differences were observed
      between the AVP groups (all P<0.05). Go6976 (5x10(-6) mol/L) and Rottlerin (10(
      5) mol/L),respectively as the specific PKC alpha and PKC Delta isoforms
      inhibitor, antagonized AVP (5x10(-10) mol/L)-induced increase in vascular
      reactivity and calcium sensitivity of SMA following hemorrhagic shock and
      inhibited AVP-induced shift to the left of cumulative concentration-response
      curve of NE and Ca2+, and the Emax was significantly decreased (P<0.05 or
      P<0.01). CONCLUSION: AVP significantly restored the decreased vascular reactivity
      and calcium sensitivity of vascular smooth muscle following hemorrhagic shock,
      and its underlying mechanisms may be related to both alpha and Delta isoforms of
      PKC activation.

PMID- 18328125
TI  - [The regulatory effect of protein kinase C epsilon on vascular reactivity and
      calcium sensitivity during hemorrhagic shock in rats].
AB  - OBJECTIVE: To observe the regulatory effect of protein kinase C epsilon (PKC
      epsilon) on vascular reactivity and calcium sensitivity following hemorrhagic
      shock. METHODS: The superior mesenteric artery (SMA) obtained from rats in
      hemorrhagic shock for different time duration (immediately, 0.5 hour, 1 hour, 2
      hours and 4 hours after shock) were adopted to determine the mRNA expression of
      PKC epsilon using reverse transcription-polymerase chain reaction (RT-PCR)
      technique, and the first branch of SMA were adopted to assay the vascular
      reactivity and calcium sensitivity by observing the contraction initiated by
      norepinephrine (NE) and Ca2+ with isolated organ perfusion system. The agonist
      and antagonist of PKC epsilon were used to observe the regulation of PKC epsilon
      on vascular reactivity and calcium sensitivity at 2 hours after hemorrhagic
      shock. RESULTS: (1) Vascular reactivity and calcium sensitivity of the first
      branch of SMA were increased at the early stage of hemorrhagic shock, and
      decreased at the late stage of hemorrhagic shock. PKC epsilon mRNA exhibited a
      time-dependent increase following hemorrhagic shock, peaked at 1 hour (P<0.01)
      and maintained at a high level at 4 hours (P<0.01). (2) The agonist of PKC
      epsilon increased the vascular reactivity and calcium sensitivity of the first
      branch of SMA, and its antagonist decreased the vascular reactivity and calcium
      sensitivity of SMA at 2 hours after shock (all P<0.01). CONCLUSION: PKC epsilon
      may be an important endogenous protective molecule. It plays an important role in
      the regulation of vascular reactivity and calcium sensitization following
      hemorrhagic shock.

PMID- 18328126
TI  - [Effect of poly-adenosine diphosphate ribosyl-polymerase on vascular
      hyporeactivity in rats with hemorrhagic shock].
AB  - OBJECTIVE: To study the effects of poly-adenosine diphosphate ribosyl-polymerase
      (PARP) on vascular hyporeactivity during hemorrhagic shock in rats. METHODS:
      Sprague-Dawley (SD) rats were randomly divided into three groups: shock, 3
      aminobenzamide (3-AB) pretreatment+shock, and sham operation. Bleeding from the
      femoral artery to induce hemorrhagic shock model. The blood pressure changes
      following 3 microg/kg norepinephrine (NE) injection were observed in vivo. The
      response of vascular rings of superior mesenteric artery (SMA) to NE was
      determined ex vivo. The nitrogen monoxide (NO) contents of plasma and tissue
      homogenate of SMA were measured using the assay kit based on the nitrate
      reductase reaction. RESULTS: The maximum increase of mean arterial pressure in
      response to NE immediately following shock in the shock group was significantly
      lower than in the sham operation group (P<0.01) and the value at 1 hour after
      blood reinfusion in the shock group was obviously lower than in the 3-AB
      pretreatment+shock group (P<0.05) and in the sham operation group (P<0.01). The
      maximum concentration force in the sham operation group [(0.367 1+/-0.221 3)g/mm]
      was significantly increased than in the 3-AB pretreatment+shock group [(0.286 4+/
      0.153 2) g/mm, P<0.05] and in the shock group [(0.185 6+/-0.111 3)g/mm, P<0.01].
      The cumulative dose-response curves of SMA to NE shifted to the left, and the
      contraction force was markedly increased as NE concentration reaching 10(-6),
      10(2+) and 10(-5) mol/L in the 3-AB pretreatment+shock group compared to the
      shock group (all P<0.05). There were no significant difference on plasma NO
      content among the three groups. However, the NO contents of plasma and tissue
      homogenate of SMA in the 3-AB pretreatment+ shock group were slightly lower than
      in the shock group (P>0.05). CONCLUSION: PARP is involved in the vascular
      hyporeactivity in hemorrhagic-shocked rats.

PMID- 18328127
TI  - [The optimal resuscitation pressure of several resuscitation fluids in
      controlling hemorrhagic shock in rats].
AB  - OBJECTIVE: To investigate the optimal mean blood pressure of different
      resuscitation fluids in resuscitating hemorrhagic shock in rats. METHODS: One
      hundred and eighty Sprague-Dawley (SD) rats were used to reproduce hemorrhagic
      shock model by 35% and 45% depletion of blood volume, and they were randomly
      divided into Lactated Ringer solution (LR), 7.5% NaCl/6% Dextran 40 (HSD), and
      LR+hydroxyethyl starch (HES) groups. Mean arterial pressure (MAP) was maintained
      at 60, 80 and 100 mm Hg (1 mm Hg=0.133 kPa) respectively with these fluids. Left
      intraventricular systolic pressure (LVSP), the maximal change rate of left
      intraventricular pressure (+/-dp/dt max), blood gases and 12-hour survival rate
      were observed. RESULTS: In 35% hemorrhagic shock rats, LR and LR+HES could better
      maintain the MAP at the set level, but HSD could not maintain MAP at 100 mm Hg,
      reaching only 85 mm Hg. In 45% hemorrhagic shock rats, LR and HSD, also could not
      elevate MAP to 100 mm Hg, and LR infusion could restore MAP to about 85 mm Hg,
      HSD to 80 mm Hg and LR+HES to 60 mm Hg. Overall 12-hour survival rate was highest
      in group with LR+HES to maintain MAP at 60 mm Hg with satisfactory hemodynamic
      parameters and blood gases. HSD group ended up with a lowest survival rate.
      CONCLUSION: Different fluids to resuscitate hemorrhagic shock showed a different
      optimal MAP. LR between 85-100 mm Hg, HSD at 80 mm Hg and LR+HES at 60 mm Hg, may
      throw better effect on resuscitating moderate and severe hemorrhagic shock.

PMID- 18328128
TI  - [Analysis of a survey of SSC guideline implemented among Chinese intensivists].
AB  - OBJECTIVE: To survey the implementation of the "surviving sepsis campaign" (SSC)
      guidelines for the management of severe sepsis and septic shock among Chinese
      adult intensive care unit (ICU). METHODS: One of the questionnaires included the
      understanding of the SSC guidelines and the diagnosis of severe sepsis and septic
      shock. The other one was about SSC 6-hour bundle and 24-hour bundle. A 5-point
      Likert scale (total understanding, partial understanding, understood, hardly
      understood, not understood) was used to elicit answers about the degree in
      perceiving the guidelines. The other 5-point Likert scale (always, often,
      sometimes, rarely, never) was used to elicit answers about the frequency of use
      of the guidelines. The answers to 3-point Likert scale were combined when the
      survey was statistically analyzed. RESULTS: The questionnaires were E-mailed to
      50 adult ICUs from June to September in 2007. A total of 224 physicians from 41
      adult ICUs participated in answering, with a response rate of 82%. Among all the
      answers, one was considered not eligible. Altogether there were forty-one ICUs
      with 512 beds, including 31 general ICUs and 10 specialty ICUs from 14 provinces
      admitting almost 20,000 patients per year. Eighty point seven percent of
      intensivists could completely understand the SSC guideline. More intensivists of
      general ICU could understand the guidelines better than intensivists of specialty
      ICU [odds ratio (OR)=2.987, 95% confidence interval (CI): 2.241-3.981, P<0.01].
      More chiefs of ICU could understand of the guidelines better than common
      intensivists (OR=1.949, 95%CI: 1.641-2.361, P<0.01). Doctors of different
      professional levels such as attending doctors vs. residents (OR=7.750, 95% CI:
      3.711-16.184, P<0.01), chief vs. residents showed different attitude toward the
      guidelines(OR=6.455, 95%CI: 3.420-12.181, P<0.01). Chiefs understand guidelines
      better than attending doctors, more attending doctors understand guidelines than
      residents. There were 80.0% intensivists always used the guidelines during work.
      There were only 46.6% intensivists believe central venous pressure, but 85.6%
      doctors were willing to use it in guiding their work. Intensivists, who could
      trust nurses to carry out the guideline, outnumbered those who did not (P=0.000).
      CONCLUSION: Guidelines for severe sepsis and septic shock guidelines was
      published in SSC Meeting in 2003. Most Chinese intensivists can understand the
      SSC guidelines and always use it during their clinical practice.

PMID- 18328129
TI  - [Hemorrheological changes in irreversible hemorrhagic shock].
AB  - OBJECTIVE: To observe the characteristics of changes in hemorheology at the early
      stage of irreversible hemorrhagic shock in a rodent model. METHODS: Rodent model
      of irreversible hemorrhagic shock was reproduced. Animals were randomized into 4
      groups. In the first group, survival rate and mean arterial pressure (MAP) in 180
      minutes were observed after hemorrhagic shock (S group). In the second group,
      animals were sacrificed soon after hemorrhagic shock (S0 group). In the third
      group, animals were sacrificed 60 minutes after hemorrhagic shock (S1 group). In
      the fourth group, animals were sacrificed 120 minutes after hemorrhagic shock (S2
      group). Blood samples of animals of S0, S1 and S2 were all obtained before
      hemorrhagic shock. Blood lactate, hemorheological parameters, red blood cell
      (RBC) deformability and RBC aggregation index were determined. RESULTS: Mean
      blood loss of S group was (22.9+/-3.8) ml/kg, constituting about (38.1+/-6.3)% of
      total blood volume. At 60, 120 and 180 minutes after hemorrhagic shock, survival
      rates were 100%, 72% and 64%, respectively. Compared with baseline, 0, 60 and 120
      minutes after hemorrhagic shock, blood lactate increased significantly (all
      P<0.01), but 120 minutes after hemorrhagic shock, it decreased significantly
      compared with 0 minute after hemorrhagic shock (P<0.05). Compared with baseline,
      0 minute and 60 minutes after hemorrhagic shock, blood viscosity was found to be
      decreased at shear rate of 10 s(-1), 60 s(-1) and 100 s(-1) (all P<0.01); 120
      minutes after hemorrhagic shock, at shear rate of 10 s-1 and 60 s(-1), blood
      viscosity decreased significantly (both P<0.01); 0, 60 and 120 minutes after
      hemorrhagic shock, plasma viscosity, RBC deformability and RBC aggregation index
      at shear rates of 600 s(-1), 800 s(-1) and 1 000 s(-1) decreased significantly
      (all P<0.01). CONCLUSION: At the early stage of irreversible hemorrhagic shock,
      blood lactate increased significantly, and decreased afterwards. These indicate
      reversal of deterioration of metabolism. At different time after the early stage
      of irreversible hemorrhagic shock, blood and plasma viscosity, RBC deformability
      and aggregation index lowered significantly and did not improve. Changes in
      viscosity and RBC aggregation are different from the changes in late stage, and
      this indicates that hemorheological disorders should be corrected in the
      treatment at the early stage after hemorrhagic shock.

PMID- 18328130
TI  - [Study on intestinal absorption rate of glucose electrolyte solution during
      enteral resuscitation of 35% total body surface area burn injury in dog].
AB  - OBJECTIVE: To investigate the intestinal absorption rate of glucose-electrolyte
      solution (GES) during enteral resuscitation of burn injury in Beagle dogs, and
      compare the effect of enteral intake with that of intravenous infusion
      resuscitation. METHODS: Twelve male Beagle dogs were subjected to a 35% total
      body surface area (TBSA) full-thickness flame III degree injury. Thirty minutes
      after burn, each dog was given either enteral resuscitation with a GES (EGES
      group) or intravenous resuscitation with lactated Ringer's solution (IVLR group),
      and the amount and speed of replenishment of fluid were in accordance with
      Parkland formula. In the first 8 hours post burn, intestinal absorption rates of
      water and Na+ were continuously assessed using phenol red as a nonabsorbable
      marker for water absorption rate. The plasma volume (PV) was measured by the dye
      (indocyanine green) dilution technique, and the plasma concentration of Na+, mean
      arterial pressure (MAP) cardiac output (CO), and urine volume were also
      determined in the first 8 hours. All above measurement were performed in animals
      without anesthesia. At the end of 8-hour-period of experiment, the remnant fluids
      in the intestine were collected to calculate the total volume of fluid absorbed
      in 8 hours. RESULTS: The intestinal absorption rates of water and Na+ reduced
      markedly down to lowest level (21% and 37% of pre-injury level) at 3.5 hours post
      burn, and then increased slowly. But the mean absorption rate of water was
      similar to infusing rate according to Parkland formula [(99+/-47) mlxh(-1)xm(-1)
      vs. (81+/-11) mlxh(-1)xm(-1), P>0.05]. The total fluid absorbed by intestine was
      (94.8+/-3.7)% of the total fluid infused within 8 hours post burn. There were no
      significant differences in plasma concentration of Na+, MAP and CO between two
      groups at 8 hours post burn. The urine volume and PV at 4 hours in EGES group
      were lower than those in IVLR group (both P<0.05), but those indexes at 8 hours
      showed no significant difference between two groups (both P>0.05). CONCLUSION:
      Intestinal absorption rate of fluid given according to Parkland formula after
      burn injury is sufficient to resuscitate shock in animals suffering from a
      35%TBSA full-thickness burn. Enteral resuscitation with GES may attain a similar
      therapeutic effect in expanding PV and maintain hemodynamic parameters.

PMID- 18328131
TI  - [Effect of carbachol on intestinal mucosa blood flow and absorption rate of
      glucose-electrolyte solution during enteral resuscitation for 50% total body
      surface area full-thickness burn injury in dog].
AB  - OBJECTIVE: To investigate the effect of carbachol (CAR) on blood flow of
      intestinal mucosa and absorption rate of glucose-electrolyte solution (GES)
      during enteral resuscitation of burn shock in dog. METHODS: Eighteen male Beagle
      dogs were subjected to a (51.2+/-2.6)% total body surface area (TBSA) full
      thickness flame injury, and fluid resuscitation was given according to Parkland
      formula 0.5 hour after burn. Animals were randomly divided into intravenous
      infusion of GES group (VGES group, n=6), enteral infusion of GES group (EGES
      group, n=6) and EGES containing 0.25 microg/kg of CAR group (EGES/CAR group n=6).
      In the first 8 hours post burn, intestinal absorption rate of water and Na+,
      intestinal mucosa blood flow (IBF), the plasma volume (PV) and plasma
      concentration of Na+ were continuously determined without anesthesia. At the end
      of 8 hours animals were sacrificed, and specimens of gut tissue were taken to
      determine the activity of Na+-K+-ATPase. RESULTS: The intestinal absorption rate
      of water and Na+ was reduced markedly after burn in two enteral resuscitation
      groups and much lower than pre-injury levels and the expected infusing rate
      according to Parkland formula. It was found that the absorption rate of water and
      Na+ from 1.5 hours and 2.5 hours in EGES/CAR group were significantly higher
      compared with those in EGES group (all P<0.05). During 8 hours after burn, only
      47.1% and 63.8% of fluids enterally infused in EGES and EGES/CAR groups were
      absorbed by the gut. The volume of fluid absorbed and the fluid absorption rate
      were significantly higher in EGES/CAR group than those in EGES group (P<0.05).
      Incidence of gut intolerance (diarrhea) was 83% in EGES group, which was higher
      than that of in EGES/CAR group (50%). IBF was significantly decreased compared
      with pre-injury levels in all groups. Enteral infusion of CAR led to a
      significant elevation of IBF in EGES/CAR compared with GES group from 4 hours
      after burn, but it was still lower than pre-injury levels and those in VGES
      group. The Na+-K+-ATPase activity between three groups ranked as follows: VGES
      group>EGES/CAR group>EGES group (P<0.05). Within 8 hours post injury, PV and
      plasma concentration of Na+ in two enteral resuscitation groups were much lower
      than those in VGES group, but from 4 hours after burn the values in EGES/CAR
      group were higher than those in EGES group (all P<0.05). CONCLUSION: 50%TBSA full
      thickness flame injury led to a markedly decrease in intestinal absorption rate
      of water and Na+. The total volume of fluid absorbed by intestine in 8 hours was
      significantly lower in enteral resuscitation groups compared to the regime of the
      Parkland formula. CAR promoted intestinal absorption rate and PV by increasing
      the intestinal blood flow and Na+-K+-ATPase activity, and it seems to exert a
      helpful effect on the resuscitation of burn shock with electrolyte solution per
      oral route.

PMID- 18328133
TI  - [Effect of carbachol on gastric emptying and gastric mucosa partial pressure of
      carbon dioxide in oral resuscitation of burn shock with a glucose-electrolyte
      solution in dogs].
AB  - OBJECTIVE: To investigate the effect of carbachol (CAR) on gastric emptying and
      gastric mucosa partial pressure of carbon dioxide (PgCO2) in the resuscitation of
      burn shock with oral administration of glucose-electrolyte solution (GES) in
      dogs. METHODS: Twenty-four adult male Beagle dogs were randomly divided into 4
      groups: 35% total body surface area (TBSA) III degree burn resuscitated with oral
      GES (35% TBSA GES, n=6), 35% TBSA III degree burn with oral GES containing 20
      microg/kg of CAR (35% TBSA GES/CAR, n=6), 50% TBSA III degree burn with oral GES
      (50% TBSA GES, n=6) and 50% TBSA III degree burn with oral GES containing 20
      microg/kg of CAR (50% TBSA GES/CAR, n=6). Dogs were subjected to 35% TBSA or 50%
      TBSA full-thickness flame injury respectively. Thirty minutes after burn, dogs
      were given GES or GES containing CAR according to Parkland formula (1/2 of 4
      mlxkg(-1)x1% TBSA(-1) within 8 hours post burn, and the remaining 1/2 within next
      16 hours post burn) by gavage. The gastric emptying rate, PgCO2 and intolerance
      symptoms were determined at 2, 4, 8 and 24 hours post burn. RESULTS: The gastric
      emptying rate was significantly decreased in all groups after the burn (P<0.05),
      and it was 51.5% at 2 hours after burn in 35% TBSA GES group and 39.2% at 4 hours
      after burn in 50% TBSA GES group. It was gradually ameliorated, but still much
      lower than pre-injury levels (both P<0.05). The gastric emptying rate in GES/CAR
      group were significantly higher at all time points after injury than those in 35%
      GES group (P<0.05), and it was higher than that in 50% GES group at 8 hours and
      24 hours (both P<0.05). The gastric emptying rate restored to pre-injury levels
      (P>0.05) in 35% GES/CAR group, and it was still lower than pre-injury level in
      50% GES/CAR group (P<0.05). The PgCO2 were significantly elevated in all groups
      post burn (all P<0.05), and could not return to pre-injury levels. The PgCO2 in
      GES/CAR group were significantly higher at all time points after injury than
      those in 35% GES group (P<0.05), and it was higher than that in 50% GES group at
      4 hours and 24 hours (P<0.05). The degree of gastric intolerance symptoms could
      be ranked as follows: 50%TBSA GES group (83.3%, 5/6)>50% TBSA GES/CAR group
      (50.0%, 3/6)>35%TBSA GES group (16.7%, 1/6)>35%TBSA GES/CAR group (0, 0/6).
      CONCLUSION: The results indicate that CAR has a significant effect in improving
      gastric emptying and gastric ischemia during oral resuscitation of burn shock
      with a glucose electrolyte solution.

PMID- 18328134
TI  - [Effect of aminoguanidine on hemodynamics and nitrogen monoxide in hemorrhagic
      shock in rabbit].
AB  - OBJECTIVE: To explore the effect of aminoguanidine (AG) on hemodynamics and
      nitric oxide (NO) in hemorrhagic shock in rabbit. METHODS: Shock was produced in
      twenty rabbits by femoral artery blood letting, and they were randomly divided
      into two groups with treatment with saline (control group) or AG (each n=10).
      Pclab system and nitric acid reductase methods were performed to detect
      hemodynamics parameters and NO levels at preshock, postshock (30 minutes and 150
      minutes) and 30 minutes and 180 minutes after resuscitation respectively.
      RESULTS: No significant differences were observed in hemodynamics parameters and
      NO levels between the two groups before resuscitation. Whereas after
      resuscitation, hemodynamics parameters such as systolic arterial pressure (SAP),
      heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure
      (LVSP) and the max and minimum first derivative of left ventricular pressure (+/
      dp/dt max) were all improved greatly in the two groups. AG decreased serum NO
      level significantly, while saline did not have such effect, suggesting that AG
      had a longer and more efficient effect against hemorrhagic shock (P<0.05 or
      P<0.01). CONCLUSION: AG can improve hemodynamics parameters and decrease NO level
      in hemorrhagic shock in rabbit.

PMID- 18328135
TI  - [Effect of propofol on gastric mucosal injury after hemorrhagic shock and
      reperfusion in rabbits].
AB  - OBJECTIVE: To study the therapeutic effect and its mechanisms of propofol on
      gastric mucosal injury after hemorrhagic shock with reperfusion in rabbits.
      METHODS: Seventy-five New Zealand healthy adult male rabbits were randomly
      divided into 5 groups of 15 rabbits each: control group (S group), model group (M
      group), pre-ischemia group (P1 group), pre-reperfusion group (P2 group) and post
      reperfusion group (P3 group). The hemorrhage reperfusion-gastric mucosal injury
      (HR-GMI) model was reproduced. In P1, P2 and P3 groups, propofol 5 mg/kg was
      injected intravenously 10 minutes before ischemia, reperfusion and 20 minutes
      after reperfusion respectively, then propofol 20 mgxkg(-1)xh(-1) was infused. In
      control and model groups, propofol was replaced with equal volume of normal
      saline. The ultrastructure change in gastric mucosa was examined, and the
      activity of superoxide dismutase (SOD) and contents of malondialdehyde (MDA) in
      serum and gastric mucosa were determined. RESULTS: (1) In M group, the most of
      the cristae and membranes of mitochondria in chief cells of gastric mucosa were
      fused or disappeared, with formation of vacuoles which induced vacuolization, and
      a part of membrane blended or disappeared, and degranulation appeared in rough
      endoplasmic reticulum in these cells. These changes in mitochondria and rough
      endoplasmic reticulum were mitigated in all propofol groups, especially in P1
      group. (2) The activity of SOD was significantly decreased and the contents of
      MDA were obviously increased in serum and gastric mucosa in M group compared with
      those in S group (all P<0.01). The activity of SOD was significantly increased
      and the content of MDA was decreased in serum and gastric mucosa in all propofol
      groups compared with those in M group (P<0.05 or P<0.01). The activity of SOD was
      higher and the content of MDA was lower in P1 group than those in P3 group (both
      P<0.05). CONCLUSION: Propofol can attenuate the gastric mucosa injury by
      eliminating oxygen free radical and preventing its generation caused by
      hemorrhagic shock and reperfusion.

PMID- 18328136
TI  - [Effects of penehyclidine hydrochloride on the splanchnic perfusion of patients
      with septic shock].
AB  - OBJECTIVE: To observe the effect of penehyclidine hydrochloride on the treatment
      of septic shock. METHODS: Forty-five patients with a confirmed diagnosis of
      septic shock were enrolled, and they were randomly and equally divided into 3
      groups, namely penehyclidine hydrochloride group, anisodamine group and control
      group (each n=15). Gastric intramucosal carbon dioxide partial pressure (PgCO2)
      was determined by gastric mucosa tonometry, partial pressure of carbon dioxide in
      arterial blood (PaCO2) was determined by blood gas analysis and then gastric
      arterial carbon dioxide partial pressure gap [P(g-a) CO2] was calculated prior to
      medication (0 hour) and 1, 6, 12 and 24 hours after medication respectively. The
      heart rate, mean arterial pressure (MAP), central venous pressure (CVP), urine
      volume, central venous oxygen saturation (ScvO2) and prognosis were observed.
      RESULTS: Compared with control group, P(g-a) CO2 decreased significantly (P<0.05,
      respectively) at each time point after medication, whereas no significant
      difference in MAP or CVP was seen between penehyclidine hydrochloride group and
      anisodamine group. No marked change in heart rate was found in penehyclidine
      hydrochloride group, but it increased significantly in anisodamine group
      (P<0.05). The number of patients that attained the traditional goal of shock
      resuscitation was 13 in penehyclidine hydrochloride group, 12 in anisodamine
      group, and 10 in control group. The incidence of compensated covert shock
      [gastric mucosa remained ischemic with normalized hemodynamic parameters, namely
      P(g-a) CO2>or=1.2 kPa] was lower in penehyclidine hydrochloride group and
      anisodamine group [7.7% (1/13), 16.7% (2/12)] than in control group [60.0%
      (6/10), P<0.05, respectively], P(g-a) CO2 in patients that attained normal
      hemodynamic parameters were lower in penehyclidine hydrochloride group and
      anisodamine group [(0.82+/-0.13) kPa and (0.91+/-0.18) kPa] than in control group
      [(1.22+/-0.21) kPa, P<0.01 and P<0.05]. The time for attaining the satisfactory
      goal of shock resuscitation was shorter in penehyclidine hydrochloride group and
      anisodamine group [(4.21+/-0.82) hours and (5.12+/-1.02) hours] than in control
      group [(6.51+/-1.22) hours, P<0.05, respectively]. However, the time to attain
      the satisfactory goal of shock resuscitation was shorter in penehyclidine
      hydrochloride group than in anisodamine group (P<0.05), but no statistically
      significant difference was found among other findings. CONCLUSION: Penehyclidine
      hydrochloride could significantly improve the microcirculation and compensated
      covert shock without adverse influence on heart rate, shortening of the time of
      shock resuscitation, and it might have the possibility of decreasing death rate
      in patients with septic shock. At present penehyclidine hydrochloride is one of
      the most promising vasoactive drugs in releasing vasoconstriction of
      microcirculation in patients with septic shock.

PMID- 18328137
TI  - [Should infusion of albumin be used in critical patients?].

PMID- 18328138
TI  - [Essentials of international guidelines for management of severe sepsis and
      septic shock 2008].

PMID- 18328139
TI  - Ultrasound imaging for the rheumatologist. XIII. New trends. Three-dimensional
      ultrasonography.
AB  - Despite its indubitable potential, ultrasonography still has limited diffusion in
      rheumatology related principally to the image acquisition process due to at least
      five main factors: the steep learning curve, lack of standardisation of the
      technique, intra- and inter-observer variability, time consumption and the high
      initial cost of top quality sonographic equipment. Of all these barriers, the
      first four are undoubtedly the most difficult to overcome. This review discusses
      the available evidence supporting the potential of three-dimensional ultrasound
      with high-frequency volumetric probe to overcome the first four barriers. The
      challenge to three-dimensional ultrasound is to prove itself to be a method that
      requires no particular skills that can be mastered in just a few minutes and is
      not operator-dependant [corrected]

PMID- 18328140
TI  - Increase of RP105-lacking activated B cells in the peripheral blood and salivary
      glands in patients with Sjogren's syndrome.
AB  - OBJECTIVE: To quantify the activated B cells in the peripheral blood and salivary
      glands of patients with Sjogren's syndrome (SS) by analyzing the expression of
      RP105 molecule on the B cells. METHODS: The expression of RP105 on the peripheral
      blood B cells of patients with SS (19 cases) was analyzed by flow cytometry.
      RP105-positive and negative B cells were sorted and cultured in vitro and the
      amount of immunoglobulins (IgG and IgM) produced in the supernatant was measured
      by enzyme-linked immunosorbent assay (ELISA). Salivary gland biopsy samples from
      9 SS patients were histologically evaluated and the sequential frozen sections
      were separately immunostained by anti-RP105 and anti-CD20 monoclonal antibodies.
      RESULTS: A significantly higher proportion of peripheral blood RP105-negative B
      cells was found in SS patients than in healthy individuals. RP105-negative, but
      not positive, B cells from SS patients were capable of producing IgG and IgM
      spontaneously in vitro, which was enhanced by the addition of Staphylococcus
      aureus Cowan I strain (SAC) or IL-6. Salivary glands from 2 of 9 SS patients were
      found to have lymphoid follicles whose germinal centers consisted of RP105
      negative B cells. Moreover, a larger proportion of B cells extensively
      infiltrating the area other than lymphoid follicles was also RP105-negative.
      CONCLUSION: RP105-negative B cells, a subset of highly activated and well
      differentiated B cells, which are increased in number in the peripheral blood and
      extensively infiltrate salivary glands, may be responsible for the production of
      class-switched immunoglobulin in SS. In addition, those cells might be associated
      with the inflammation and tissue damage of the salivary glands.

PMID- 18328141
TI  - MEFV mutation analysis of familial Mediterranean fever in Japan.
AB  - BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disease
      characterized by recurrent attacks of fever with serosal inflammation. FMF gene
      (MEFV) mutations have been identified primarily in patients from Mediterranean
      populations. Although several clinical cases have been reported in Japan, there
      have been few reports to date on mutation analysis. We studied FMF patients and
      their relatives to examine the clinical and genetic features of this disease in
      the Japanese population. METHODS: Twelve Japanese FMF patients who met the Tel
      Hashomer criteria and a total of 17 relatives from 5 of 10 families underwent
      molecular genetic studies to detect MEFV mutations. The characteristics of these
      Japanese FMF patients and geno-phenotypical correlations were examined. RESULTS:
      Almost all of our patients had been suffering for a long time from fever of
      unknown origin and one patient also had systemic amyloidosis. In our 12 FMF
      patients, we detected the substitutions E84K, L110P, E148Q, R761H and M694I. We
      also newly diagnosed 2 relatives as having FMF based on clinical symptoms and the
      existence of FMF mutations. One patient was homozygous for E148Q, the patient
      with systemic amyloidosis was a homozygote for M694I and 4 patients from 3
      families were compound heterozygotes for E148Q and M694I. Three patients in one
      family were compound heterozygotes for E148Q, L110P and M694I. There were 3
      patients who were heterozygous for E84K, L110P-E148Q or M694I and had no other
      nucleotide changes in the exons of MEFV. On the other hand, 2 relatives who had
      never experienced symptoms of FMF were homozygous for L110P-E148Q as well as
      compound heterozygous for E148Q/E148Q-R761H. E148Q and M694I were the most
      frequently detected substitutions in our study. CONCLUSIONS: MEFV mutations occur
      in Japanese FMF patients though FMF is rare in Japan. The identification of MEFV
      mutations could be a reliable diagnostic test for FMF. The results of genetic
      analyses on 14 Japanese FMF patients in this study revealed that E148Q and M694I
      are frequent alleles.

PMID- 18328142
TI  - Maintenance and tolerability of infliximab in a cohort of 152 patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To determine the maintenance, tolerability and safety of infliximab in
      an unselected cohort of patients with rheumatoid arthritis (RA). PATIENTS AND
      METHODS: One hundred and fifty-two RA patients receiving at least one course of
      infliximab between 2000 and 2003 were included in this study. Response to
      treatment and safety were assessed through recording adverse events, physical
      examinations and standard laboratory tests. The dosage of infliximab was patient
      specifically modified, when therapeutic response was judged inadequate by the
      assessment of a physician. RESULTS: The mean duration of follow-up was 401 days
      (85-1221). One hundred and twenty-two patients (78%) continued to receive
      infliximab after one year. 40 patients (26.3%) stopped infliximab therapy: 14
      (9.2%) for inefficacy, 21 (13.8%) for adverse events. Fifty nine patients (38.8%)
      required an increase of the dosage (n=23, 15%) or a shortening of the interval
      between the infusions (n=20, 13.2%), or both (n=16, 10.5%) for symptomatic
      control. Infliximab discontinuation tended to be more frequent in smokers
      (p=0.055). Ninety-four patients (62%) reported at least one adverse event during
      the study: 64 infections (43%), 35 infusion reaction events (23%) which led to a
      discontinuation for 10 patients. Infusion reactions were more frequent in
      patients with a history of allergy. Three cases of tuberculosis and 1 breast
      carcinoma were reported during the study. CONCLUSIONS: Adjustments in the
      treatment of RA patients treated with recommended doses of infliximab were common
      (38.8% of the treated patients). Furthermore, the observed rate of infections
      (43%), including three cases of tuberculosis, should alert physicians to be
      vigilant in the routine care of patients treated with infliximab.

PMID- 18328143
TI  - Resource utilization and the cost of rheumatoid arthritis in Brazil.
AB  - OBJECTIVE: To describe and analyze resource utilization in patients with
      rheumatoid arthritis (RA) treated at a tertiary public health facility over a one
      year period. Costs for the patient and for society associated with the treatment
      of RA were also investigated. METHODS: One hundred consecutively selected RA
      patients were included. Resource utilization was evaluated retrospectively for
      one year. Systematic interviews were used in all patients and demographic,
      socioeconomic and clinical variables were recorded. RESULTS: One hundred patients
      were included. Most of the patients were women (92%) and had mean age and disease
      duration of 51 and 11 years, respectively. The majority of the patients were
      Steinbroker functional class I (48%). Mean HAQ score for the sample was 0.95 and
      mean Short-Form-36 scores were between 49.64 (bodily pain) and 70.00 (social
      functioning). The average monthly household income for the group was US$ 359. The
      patients had on average 4 outpatient visits and 21 laboratory exams per year.
      Drugs accounted for 59% of the total cost associated with RA. The average total
      cost for society was US$ 424.14 per patient per year, of which 95% were direct
      and 5% indirect costs. CONCLUSION: The management of RA patients is an important
      financial burden in Brazil. The effort to couple resource utilization with the
      best available evidence, associated with the limited funds available in the
      healthcare system (particularly in a developing country), emphasizes the
      importance of studies that critically evaluate resource utilization and cost in
      these chronic patients. The systematic use of such studies may prove helpful to
      optimize the health system.

PMID- 18328144
TI  - Prevalence of and risk factors for the metabolic syndrome in women with systemic
      lupus erythematosus.
AB  - OBJECTIVE: To examine the prevalence of the metabolic syndrome and the
      relationship between metabolic syndrome score (MetS score) and disease
      characteristics and cardiovascular events (CVEs) in women with SLE. METHODS:
      Demographic and clinical data were collected in 141 female SLE patients. The
      prevalence of the metabolic syndrome was defined by a modified National
      Cholesterol Education Program (NCEP/ATP III) definition. Metabolic syndrome was
      defined as MetS score >or= 3. RESULTS: Twenty-three (16%) of the 141 SLE patients
      (mean age 39+/-12 years, mean disease duration 6.2+/-6.6 years) fulfilled the
      criteria of the metabolic syndrome. The mean MetS score was significantly higher
      in patients with SLE and a history of cardiovascular events (CVEs) than in those
      without a previous CVE. In linear multiple regression analysis, a high MetS score
      was significantly associated with previous intravenous methylprednisolone use,
      older age, higher ESR, higher C3 levels and higher serum creatinine levels.
      CONCLUSIONS: In our female SLE patients, a high prevalence of the metabolic
      syndrome was found as compared to healthy women in the Amsterdam Growth and
      Health Longitudinal Study. Independent risk factors for high MetS score in
      patients with SLE are previous treatment with intravenous methylprednisolone,
      renal insufficiency, older age, higher ESR and higher C3 levels. These results
      suggest that assessment of the metabolic syndrome in patients with SLE might be
      important to identify subgroups of patients that are at disproportional high risk
      of developing cardiovascular disease and diabetes mellitus.

PMID- 18328145
TI  - Nottingham health profile questionnaire incorporates important aspects of the
      patient perspective into outcome assessment in rheumatoid arthritis.
AB  - OBJECTIVE: There is a consensus on the need for a more thorough assessment of
      outcome of RA from the perspective of those who experience the disease. Our
      objective was to assess the health- related quality of life (HR-QOL) of RA
      patients by the Nottingham Health Profile (NHP), the measurement of subjective
      experienced distress. METHODS: One hundred and nineteen consecutive out-patients
      were cross-sectionally assessed. HR-QOL was evaluated by using the first section
      of the NHP, a generic quality of life instrument, that assess subjective distress
      on six dimensions: mobility, pain, energy, sleep, emotional reaction and social
      isolation. Functional capacity was measured by the Health Assessment
      Questionnaire (HAQ). RESULTS: The NHP scores for mobility, pain, energy and sleep
      showed a linear association (p<0.001 for each) with HAQ disability level. In
      addition to pain, patients with mild disability (HAQ 0-1) may suffer from
      remarkable fatigue (loss of energy) and problems in sleep. Even at the HAQ level
      0, there was some perceived distress in almost all of the NHP dimensions.
      CONCLUSIONS: Poor HAQ levels were associated with patient perceived distress in
      dimensions which are getting minor attention in clinics, i.e., energy and sleep.
      It is to be noted that RA patients who reported no disability or its lowest
      levels measured by HAQ perceived notable distress in many NHP dimensions. Our
      results suggest that NHP is a potential candidate for a HR-QOL questionnaire
      which should considered to be used in routine clinical assessment of RA patients.

PMID- 18328146
TI  - Pattern of use, economic burden and vial optimization of infliximab for
      rheumatoid arthritis in Italy.
AB  - OBJECTIVE: The aim of this study was to retrospectively examine the pattern of
      utilization in clinical practice and the costs of therapy of infliximab in the
      treatment of refractory rheumatoid arthritis (RA). METHODS: Ninety-five RA
      patients (22 newly treated and 73 maintenance patients) who received at least one
      infliximab infusion during a selected observation period of one year were
      studied. After induction phase, infliximab was given at initial dose of 3 mg/kg
      every 8 weeks. Based on clinical efficacy measured by Disease Activity Score 28
      (DAS 28) index, dose adjustments were performed by increasing pro kg dose and/or
      reducing infusion interval. Overall one-year's treatment costs were also
      examined. RESULTS: Sixteen (17%) out of 95 patients discontinued treatment before
      the end of the study owing to lack of efficacy (15) or adverse events (1).
      Thirteen (59%) out of 22 newly treated patients experienced treatment escalation
      in the first year of therapy by increasing dose (13.6%), reducing interval (9%),
      or both (36.3%). The mean infliximab dose administered to all the patients was
      3.57 mg/kg and the mean infusion interval was 50 days. Considering all
      expenditure items, the mean year treatment cost per patient was euro 8454,65.
      Infliximab vial optimization allows us to reduce this amount to euro 7505,85,
      with a significant saving of euro 948,80 per patient/year. CONCLUSIONS: In this
      observational study, adjustments in infliximab treatment in the first year of
      therapy were common. Despite dose escalation, the mean dosing schedule does not
      significantly differ from those recommended in the product label. The cost of
      treatment could be reduced by using infliximab vial optimization.

PMID- 18328147
TI  - Increased basal phosphorylation of mitogen-activated protein kinases and reduced
      responsiveness to inflammatory cytokines in neutrophils from patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: We studied the functions of peripheral blood (PB) and synovial fluid
      (SF) neutrophils from patients with rheumatoid arthritis (RA), focusing the
      molecular basis for the activated state and the functional responsiveness of RA
      neutrophils to inflammatory cytokines. METHODS: Paired samples of PB neutrophils
      and SF neutrophils from the inflamed knee joint were obtained from 18 RA patients
      (5 males and 13 females). RESULTS: RA neutrophils exhibited increased spontaneous
      superoxide (O2-) release and adherence, increased basal phosphorylation of
      extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      kinase, accelerated spontaneous apoptosis, and enhanced O2- release in response
      to N-formyl-methionyl-leucyl-phenylalanine as compared with healthy normal PB
      neutrophils. When challenged with granulocyte colony-stimulating factor (G-CSF),
      granulocyte-macrophage CSF (GM-CSF) or tumor necrosis factor alpha (TNF-alpha),
      RA neutrophils exhibited reduced responses to these cytokines, which included O2-
      release, adherence, priming for enhanced O2- release, and phosphorylation of ERK
      and p38. The functional alterations were greater in SF neutrophils than in PB
      neutrophils from RA. Reduced responsiveness to cytokines in RA neutrophils was
      closely associated with increased serum and SF levels of GM-CSF and TNF-alpha. RF
      and RAHA titers were closely correlated with increased TNF-alpha level in SF.
      CONCLUSION: These findings indicate that RA neutrophils are in the activated
      state with increased basal phosphorylation of ERK and p38, and exhibit reduced
      responsiveness to inflammatory cytokines (G-CSF, GM-CSF and TNF-alpha) and
      accelerated spontaneous apoptosis.

PMID- 18328148
TI  - No influence of SLC22A4 C6607T and RUNX1 G24658C genotypic variants on the
      circulating carnitine ester profile in patients with rheumatoid arthritis.
AB  - OBJECTIVE: In a Japanese study, the C6607T SNP mapping to intron 1 of the SLC22A4
      gene encoding the OCTN1 protein was found to be associated with rheumatoid
      arthritis. Similarly, a G24658C transversion in intron 6 of the gene encoding the
      RUNX1 transcription factor that regulates OCTN1 and also likely OCTN2 expression
      was also found to confer susceptibility to the disease. METHODS: We investigated
      the prevalence of these two SNPs by RFLP analysis in a cohort of 209 Hungarian
      rheumatoid arthritis patients, and 217 healthy controls. Since both the OCTN1 and
      OCTN2 play a central role in the transmembrane transport of carnitine, we also
      determined the quantitative serum carnitine ester profile by ESI tandem mass
      spectrometry. RESULTS: No statistically significant differences were found
      comparing the genotype prevalence rates between the patients and the controls for
      either the SLC22A4 genotypes or for the RUNX1 SNPs. There was no significant
      difference in the serum carnitine ester profile when the rheumatoid arthritis
      patients were compared with the controls; furthermore, no significant difference
      in the carnitine esters could be detected when genotype specific subgroups of the
      patients and the controls were studied. CONCLUSION: Data of the current study do
      not confirm the universal and population independent susceptibility role of the
      SLC22A4 C6607T and RUNX1 G24658C variants for rheumatoid arthritis; furthermore,
      the data presented here show, that there are no significant carnitine-metabolism
      associated functional consequences of the different genotypes evidenced by the
      lack of detectable differences in the carnitine ester profiles.

PMID- 18328149
TI  - Factors influencing calcaneus quantitative ultrasound measurements in an urban
      population.
AB  - OBJECTIVE: To estimate the effect of demographic, social, behavioural and
      anthropometric factors on quantitative ultrasound (QUS) parameters in an urban
      population. METHODS: Cross-sectional evaluation of consecutive subjects selected
      as part of the EPIPorto study, Portugal. Information was obtained on demographic,
      social, clinical and behavioural characteristics using a standard protocol.
      Calcaneus QUS parameters (Broadband Ultrasound Attenuation-BUA, and Speed of
      Sound-SOS) were obtained for men and women, stratified by age group. Comparisons
      according to exposure levels were made using the Kruskal-Wallis test and the
      multivariate effect on QUS parameters was estimated by linear regression.
      RESULTS: 1482 consecutive subjects (1010 females and 472 males), aged from 18 to
      92 years. Higher levels of QUS parameters were found in the younger groups and
      progressive decrease with age were reported. Men showed higher values as compared
      to women in all parameters and differences between them increased with age.
      Differences were significant for BUA after the age of 39 and for SOS after the
      age of 59. In women, the multivariate model showed that age, body mass index
      (BMI) and smoking status were independent predictors of BUA and SOS. In men, age,
      BMI and calcium intake were significantly associated with BUA and SOS.
      CONCLUSION: The reference values in our Portuguese population are similar to
      others obtained in Southern European countries. In the Portuguese population, QUS
      parameters have age, sex and BMI as its major determinants. In addition, BUA and
      SOS may reflect specific bone characteristics influenced by a different set of
      independent determinants.

PMID- 18328150
TI  - Reduction of oxidative stress marker levels by anti-TNF-alpha antibody,
      infliximab, in patients with rheumatoid arthritis.
AB  - OBJECTIVE: The aim of this study was to evaluate the effects of anti-TNF-alpha
      antibody, infliximab, on oxidative stress markers representing DNA damage, lipid
      peroxidation, and glycoxidation. METHODS: Twenty-three RA patients underwent
      infliximab treatment and were analyzed for 30 weeks. Six patients who experienced
      side effects and one patient who had a reduced efficacy of infliximab were
      discontinued the infliximab treatment at 30-54 weeks. Sixteen patients were
      analyzed for 54 weeks. The levels of serum total, urinary total, and free
      pentosidine, which is an advanced glycation end-product (AGE), and of urinary 15
      Isoprostane F2t and 8-hydroxy-deoxy guanosine (8-OHdG) were determined at
      baseline and at 14, 30, and 54 weeks after initial treatment with infliximab.
      RESULTS: Serum total, urinary total, and free pentosidine levels were reduced at
      54 weeks after initial infliximab treatment. Urinary 15-Isoprostane F2t and 8
      OHdG levels were also reduced at 14, 30, and 54 weeks. Urinary 8-OHdG levels in
      RA patients correlated with CRP and the Disease Activity Score of 28 joints.
      CONCLUSION: In RA patients, infliximab plays an essential role as an anti
      oxidative agent against AGE formation, oxidative DNA damage and lipid
      peroxydation.

PMID- 18328151
TI  - Effectiveness of a back school program in low back pain.
AB  - OBJECTIVES: To evaluate the effectiveness of a back school program in pain,
      functional status, quality of life, and in anxiety and depression in patients
      with non-specific low back pain. METHODS: Sixty patients with low back pain were
      randomized to an intervention and control group. The intervention group underwent
      a five-weekly back school program. The control group was seen in weekly medical
      visits, without educative approaches. Both groups took acetaminophen as analgesic
      medication. All subjects were evaluated by a blind physiotherapist after
      randomization, 30, 60 and 120 days. Rolland-Morris, SF-36, STAI and Beck
      questionnaires, pain visual analogical scale and Schober's test were applied. Non
      steroidal anti-inflammatory drugs (NSAID) consumption was considered co
      intervention. The statistical analyses were performed using Pearson's Chi-Square
      analysis and Student's t-test to compare the baseline characteristics of the
      groups and the analysis of variance (ANOVA) with repeated measures to assess
      changes inter/intra groups. RESULTS: There were no significant differences in the
      baseline characteristics between the two groups. Fifty-five patients completed
      the study. The intervention group showed a significant improvement in the general
      health domain, assessed by SF-36, and also in the reduction of acetaminophen and
      NSAID intake. There was no significant difference between the groups in pain,
      functional status, anxiety or depression. CONCLUSION: The back school program was
      more effective than any educational intervention in general health status and in
      decreasing acetaminophen and NSAID intake. It was ineffective in the other
      quality of life domains, in pain, functional status, anxiety and depression.

PMID- 18328152
TI  - Treatment of rheumatoid arthritis patients with anti-TNF-alpha monoclonal
      antibody is accompanied by down-regulation of the activating Fcgamma receptor I
      on monocytes.
AB  - OBJECTIVES: To study the effect of anti-TNF-alpha therapy on activating IgG Fc
      receptor (FcgammaR) expression on monocytes of RA patients in relation to changes
      in disease activity. METHODS: RA patients were treated with anti-TNF-alpha mAb
      (infliximab). At baseline, 2 and 14 weeks after the start of anti-TNF-alpha
      treatment, FcgammaR expression levels on circulating monocytes were evaluated.
      Changes in expression were correlated to changes in disease parameters. To study
      the direct effects of TNF-alpha blockade on monocytic FcgammaR expression levels,
      monocytes were isolated and cultured with anti-TNF-alpha mAb. The effects were
      compared with those induced by TNF-alpha. RESULTS: Two weeks after the start of
      anti-TNF-alpha mAb therapy, monocytic FcgammaRI expression levels were decreased,
      whereas FcgammaRIIa and IIIa expression levels were unchanged. At 14 weeks, 8
      weeks after the last gift of anti-TNF-alpha mAb, FcgammaRI expression levels
      returned to baseline levels. FcgammaRIIa and IIIa expression levels remained
      unchanged. The change in FcgammaRI correlated with changes in CRP and ESR levels.
      In vitro, anti-TNF-alpha mAb treatment did not alter expression of FcgammaRI on
      monocytes, but increased FcgammaRIIa and IIIa. TNF-alpha down-regulated all
      activating FcgammaRs, mainly FcgammaRIIa and IIIa, but also the inhibitory
      FcgammaRIIb. CONCLUSION: Anti-TNF-alpha mAb treatment of RA patients is
      accompanied by down-regulation of FcgammaRI expression levels on monocytes. This
      is likely an indirect effect of TNF-alpha blockade on disease activity, since in
      vitro anti-TNF-alpha mAb does not directly change FcgammaRI expression on
      monocytes. In contrast, TNF-alpha down-regulated all activating FcgammaRs. Thus,
      blocking TNF-alpha may relieve the negative feedback mechanism of TNF-alpha as
      down-regulator of FcgammaRs. Strategies to reduce activating FcgammaRs may have
      additional value in the treatment of RA patients with TNF-alpha blockade by
      diminishing immune complex-mediated activation of monocytes/macrophages.

PMID- 18328153
TI  - Activation of nuclear factor kappa B and mitogen activated protein kinases in
      psoriatic arthritis before and after etanercept treatment.
AB  - OBJECTIVE: To study activation of intracellular pathways depending on nuclear
      factor kappa B (NFkappaB) and mitogen activated kinases (MAPK) in the synovium of
      patients with psoriatic arthritis before and after treatment with etanercept.
      METHODS: Synovial biopsies were obtained by needle arthroscopy of the knee in 9
      patients with active psoriatic arthritis before the initiation of etanercept.
      Follow-up biopsies were taken in the same knee after 6 months. Synovitis was
      studied by histology. Pathway activation was studied by immunofluorescense for
      phosphorylated ERK, phosphorylated p38, phosphorylated JNK or phosphorylated
      inhibitor of kappa B (IkappaBalpha) using digital image analysis. RESULTS:
      Histological severity scores were significantly reduced after etanercept
      treatment. Activation of NFkappaB signaling was found in the lining layer, and in
      infiltrating and peri-vascular cells in the sublining zone. Activated p38 was
      present in both lining and sublining layer. In the sublining layer, positive
      cells were found in inflammatory infiltrates, in perivascular zones and in the
      endothelium. Activated ERK was mainly present in the sublining layer, both in
      mononuclear cell infiltrates and perivascularly. Occasional positive cells were
      found in the lining layer. Activation of JNK was recognized in cells of the
      lining layer, in some of the sublining cell infiltrates and the perivascular
      compartment. CONCLUSIONS: Etanercept therapy resulted in a significant decrease
      in NFkappaB, JNK and ERK, but not in p38 activation. Persistent activation of
      these pathways, albeit reduced, may trigger positive feedback loops and flares of
      arthritis after cessation of etanercept.

PMID- 18328154
TI  - In etanercept-treated psoriatic arthritis patients clinical improvement
      correlated with an increase of serum cortisol relative to other adrenal hormones.
AB  - OBJECTIVE: In patients with rheumatoid arthritis (RA), long-term therapy with
      anti-tumor necrosis factor (TNF) antibodies sensitizes the pituitary gland and
      improves adrenal androgen secretion in prednisolone-naive patients. However,
      whether this is similar in psoriatic arthritis (PsA) is not known. The aim of
      this study was to assess the effect of 12 weeks of etanercept treatment upon the
      function of the HPA axis in patients with PsA. METHODS: Eleven prednisolone-naive
      patients (mean age 47.3+/-8.9 years) with PsA were included. We measured serum
      levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17OHP),
      cortisol, and androstenedione (ASD), at baseline and at 4 and 12 weeks after
      initiation of anti-TNF therapy (etanercept, 50 mg every week as a single dose by
      sc. injection). Clinical improvement was assessed using the Disease Activity
      Score-28 (DAS-28). RESULTS: Mean levels of serum ACTH, serum cortisol, serum
      17OHP and serum ASD did not markedly change during 12 weeks of etanercept
      treatment. Similarly, the ratio of serum cortisol divided by serum ACTH did not
      change during 12 weeks of anti-TNF treatment. However, an increase of serum
      cortisol relative to serum 17OHP or ASD was related to clinical improvement. This
      indicates that improvement was linked to higher serum cortisol levels relative to
      others adrenal hormones. CONCLUSION: This is the first study to demonstrate
      baseline serum levels and the course of HPA axis-related hormones in patients
      with PsA. An increase of serum cortisol relative to others adrenocortical
      hormones (i.e., androstenedione and ACTH) was accompanied by clinical
      improvement.

PMID- 18328155
TI  - Is the heart affected in primary Sjogren's syndrome? An echocardiographic study.
AB  - OBJECTIVE: To evaluate whether patients with primary Sjogren's syndrome without
      overt cardiac disease have echocardiographic abnormalities and their relation
      with clinical and laboratory data. METHODS: One hundred and seven consecutive
      patients with primary Sjogren's syndrome and 112 healthy controls, matched for
      age and gender, underwent complete echocardiographic study. RESULTS: Thirty-two
      patients had mitral valve regurgitation (p<0.001) whereas tricuspid and aortic
      valve regurgitation were, also, more frequent in the patient group (p=0.022 and
      p=0.007 respectively). In multivariate analyses, low C4 levels of complement and
      age were strong predictors of mitral valve regurgitation whereas age was
      predictor of aortic valve regurgitation. Tricuspid valve regurgitation was
      associated with pulmonary hypertension. Clinically silent pericardial effusion,
      found in 9 patients (p=0.008), was associated with cryoglobulinemia and primary
      biliary cirrhosis. Twenty-four patients had pulmonary hypertension (p<0.001)
      whereas hypocomplementemia and cryoglobulinemia were strong predictors of
      pulmonary artery systolic pressure. The analyses reveal that easy fatigability
      was associated with pulmonary hypertension and low C4 levels. The patients' left
      ventricular mass index differed significantly from the controls (108.9+/-17.21
      gm(-2) vs. 85.8+/-6.73 gm(-2), p<0.001) and was associated with palpaple purpura
      and anti-Ro/SSA. From the diastolic function indices only the left ventricular
      isovolumic relaxation time differed significantly among patients and controls.
      CONCLUSION: Valvular regurgitation, pericardial effusion, pulmonary hypertension
      and increased left ventricular mass index occur with disproportionately high
      frequency in patients with primary Sjogren's syndrome and no clinically apparent
      heart disease. Thus echocardiographic studies may need to be performed in these
      patients especially when palpable purpura, antibody reactivity and low C4 levels
      are present.

PMID- 18328156
TI  - Glucocorticoid treatment in rheumatoid arthritis: low-dose therapy does not
      reduce responsiveness to higher doses.
AB  - BACKGROUND: Despite low-dose gluco-corticoid (GC) treatment, many patients with
      rheumatoid arthritis (RA) require additional flare therapy with GC at higher
      doses. Since low dose GC has been suggested to confer resistance to higher doses,
      we aimed to assess if resistance was detectable on the clinical level in patients
      with active RA. METHODS: Eighty-nine patients with active RA (Disease Activity
      Score 28, DAS28>3.2; mean age 54.5 years, mean duration of RA 9.7 years) were
      consecutively enrolled into a one-week trial of a total of 250 mg prednisolone.
      We compared improvement of the DAS28 and the Simplified Disease Activity Index
      (SDAI) in groups of patients with (n=41) and without (n=48) low-dose GC at
      baseline (by t-test). In addition, we analyzed changes of all individual core set
      measures of disease activity using multivariate statistics. RESULTS: All
      clinical, serological and functional measures improved significantly over one
      week (p<0.001). Baseline RA activity of patients with and without low-dose GC was
      on average +/- standard deviation similar among the two groups (DAS28: 4.8+/-1.2
      and 4.9+/-1.1; mean SDAI: 26.1+/-14.0 and 25.9+/-13.0, respectively), and
      likewise there was no difference between the two groups in the final disease
      activity reached, for both the DAS28 (1.4+/-1.1 vs. 1.1+/-1.0; p=0.14) and the
      SDAI (11.1+/-13.4 vs. 11.1+/-11.4; p=0.99). Improvement in all individual
      measures was also not different using a multivariate model (p=0.26). CONCLUSION:
      Pre-treatment with low-dose GC does not appear to portend GC resistance at least
      clinically, since the responsiveness to GC boosts is unaffected.

PMID- 18328157
TI  - Isotype switching and titer variation of anti-Ro/SSA antibodies over time in 100
      patients with undifferentiated connective tissue disease (UCTD).
AB  - OBJECTIVE: To correlate the clinical course of the disease with the titer, the
      isotype profile and the switch of the anti-Ro/SSA antibodies in a cohort of
      patients affected by UCTD. METHODS: One hundred selected patients with anti
      Ro/SSA antibodies detected by counterimmunoelectrophoresis (CIE), and affected by
      UCTD with a mean follow-up of 7.6 years (SD 4.8 yrs.), were studied. The titer of
      IgA, IgG and IgM anti-Ro/SSA antibodies was determined in two different sera,
      obtained at the time of diagnosis and at the last visit, by ELISA with Ro/SSA
      recombinant proteins as substrate. RESULTS: Thirty-five patients evolved from
      UCTD to a different connective tissue disease, while 65 showed a stable disease.
      Anti-Ro/SSA antibodies were detected in 91% and 97% of the patients, at baseline
      and during follow-up, respectively. IgG dominates the anti-Ro response. The titer
      of IgA, IgM and IgG anti-Ro/SSA did not differ significantly between the two
      groups of patients with UCTD. An increasing trend of IgG and IgA anti-Ro/SSA
      titer could be detected in patients evolving in primary Sjogren's Syndrome (pSS),
      but only the increase of IgG anti-Ro/SSA was significant (p=0.0235). CONCLUSION:
      IgG dominates the anti-Ro/SSA response in patients with UCTD. No substantial
      change of the antibody isotype against Ro/SSA peptides could be observed during
      follow-up. The titer of IgG anti-Ro/SSA significantly raised in the group of
      patients evolving in pSS.

PMID- 18328158
TI  - Determination of anti-cyclic citrullinated peptide antibodies in the sera of
      patients with liver diseases.
AB  - OBJECTIVE: To determine the frequency of anti-cyclic citrullinated peptide (anti
      CCP) antibodies in patients with HCV infection, primary biliary cirrhosis (PBC)
      and type-I autoimmune hepatitis (AIH) to assess the specificity of anti-CCP
      antibodies. METHODS: Rheumatoid factor (RF) and anti-CCP antibodies were measured
      in the sera from patients with HCV infection (n=45), PBC (n=73), AIH (n=55) and
      rheumatoid arthritis (n=48), and also from the sera of healthy subjects (n=23).
      Anti-CCP antibodies were measured using a second generation enzyme-linked
      immunosorbent assay (ELISA). RESULTS: No sera with elevated anti-CCP were found
      in the patients with HCV infection. Two PBC patients (2.7%) and six AIH patients
      (10.5%) had anti-CCP antibodies. The seropositivity for anti-CCP in these
      autoimmune disease patients was associated with a high frequency of RA
      association [PBC; 100% (2/2), AIH; 86.4% (5/6)]. CONCLUSIONS: Although anti-CCP
      antibodies may be present in patients with autoimmune liver diseases, almost
      seropositive patients had concomitant RA. As a result, the measurement of anti
      CCP antibodies may therefore be helpful for accurately diagnosing RA in patients
      with these liver diseases.

PMID- 18328159
TI  - Synovitis-acne-pustulosis-hyperostosis-osteitis syndrome and psoriatic arthritis
      exhibit a different immunogenetic profile.
AB  - BACKGROUND AND OBJECTIVES: Patients with psoriatic arthritis (PsA) as well as
      those with synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome
      share some common features, and in fact, for many authors the SAPHO concept fits
      well into the broader concept of PsA. However, some clinical features are unique
      to the SAPHO syndrome, and in the other hand, these patients do not show the
      known association between the HLA-B27 antigen and the spondyloarthropathies. To
      date, there are no studies comparing the immunogenetic profile of these two
      conditions, so the main objective of the present report was to analyse whether or
      not both entities may share the same genetic basis. PATIENTS AND METHODS: All
      patients with SAPHO syndrome (n=25) seen in a single university hospital from
      1985 to 2005 were recruited and followed up in standardised manner in order to
      study their main characteristics and HLA profile. The HLA-Cw6, DR and B27 antigen
      distribution of these cases was compared to that of 50 patients with psoriasis
      vulgaris, 120 with PsA, and 170 healthy blood donors. PsA patients were
      classified in accordance with their predominant pattern observed in the last 5
      years of disease evolution. Odds ratios (OR) values were calculated to measure
      the strength of the association between HLA antigens and disease, while the
      statistical significance of the association was assessed with a two-tailed
      Fisher's exact test. P<0.05 values were considered significant. RESULTS: No
      association was found between HLA-Cw6, B27, or DR antigens, and SAPHO syndrome.
      HLA-Cw6 was strongly associated with psoriasis, OR 12 (95% CI: 5.6-26, p<0.0001)
      and PsA, OR 10 (95% CI: 5.4-19.5, p<0.0001), however this antigen was equally
      distributed among the three articular categories of PsA. HLA-DR4 was found under
      represented in PsA patients compared to controls, OR 0.4 (95% CI: 0.2-0.7,
      p=0.002). HLA-DR7 correlated well with psoriatic oligoarthritis, OR 9.6 (95% CI:
      2.9-28, p<0.0001), HLA-DR8 was found associated with polyarthritis, OR 6.7 (95%
      CI: 2-25, p=0.002), while HLA-B27 was over-represented in psoriatic spondylitis,
      OR 10 (95% CI: 3.3-25, p<0.0001). CONCLUSIONS: Psoriasis/PsA and SAP-HO syndrome
      show a different immunogenetic background, however the genetic basis of SAPHO
      syndrome remains unknown.

PMID- 18328160
TI  - Thrombotic microangiopathy in patients with phosphatidylserine dependent
      antiprothrombin antibodies and antiphospholipid syndrome.
AB  - Thrombotic microangiopathy (TMA) is a rare disorder characterized by
      microvascular thrombosis. TMA has been reported in patients with antiphospholipid
      antibodies and/or antiphospholipid syndrome but its pathogenesis is not
      clarified. We present two patients with TMA associated with IgG
      phosphatidylserine dependent antiprothrombin antibodies (aPS/PT). CASE 1: A 44
      year-old Japanese female with systemic lupus erythematosus (SLE) and positive
      lupus anticoagulant (LA) was started on ticlopidine after having stroke. Four
      weeks later she developed TMA. IgG/M/A anticardiolipin antibodies (aCL) were
      negative, but strong positive IgG aPS/PT were detected. CASE 2: A 32-year-old
      Russian female with SLE was admitted because of hypertension, renal insufficiency
      and proteinuria at 14 weeks of pregnancy. She developed TMA after surgical
      abortion. IgG aPS/PT and LA were strongly positive but IgG/M/A aCL were negative.
      Neither case had von Willebrand factor cleaving protease (ADAMTS-13), suggesting
      that TMA in those patients was associated with thrombophilia rather than
      insufficient ADAMTS-13. Both patients were successfully treated with a series of
      plasma exchange.

PMID- 18328161
TI  - Aggressive transformation of a quiescent primary bone lymphoma simulating Paget's
      disease.
AB  - Primary multifocal osseous lymphoma is a rare and poorly recognized entity. Here,
      we present an instructive case of a young man who, six years after a local
      contusion of the left ankle, developed a painful polylobulated large soft tissue
      mass. This mass turned out to have arisen from the transformation of a centro
      follicular non-Hodgkin's lymphoma into a diffuse large B-cell lymphoma involving
      the calcaneus, talus, cuboid and navicular bones. The diagnostic difficulties as
      well as the implications of this aggressive transformation are highlighted here.

PMID- 18328162
TI  - Complete remission in refractory relapsing polychondritis with intravenous
      immunoglobulins.

PMID- 18328163
TI  - The regulation of the ADAMTS4 and ADAMTS5 aggrecanases in osteoarthritis: a
      review.
AB  - Destruction of articular cartilage is a key feature of a number of arthritides,
      osteoarthritis prominent among them. Aggrecan degradation, caused by increased
      activity of proteolytic enzymes that degrade macromolecules in the cartilage
      extracellular matrix, is followed by irreversible collagen degradation. The
      degradation of aggrecan is mediated by various matrix proteinases, mainly the
      aggrecanases, multidomain metalloproteinases belonging to the ADAMTS (a
      disintegrin and metalloproteinase with thrombospondin motifs) family. There has
      been much interest in the possible role of these aggrecanases, mainly ADAMTS4 and
      ADAMTS5, as therapeutic targets in osteoarthritis. There is still debate which of
      them is the major aggrecanase in osteoarthritis, however, as well as major issues
      concerning how they are regulated, with possible discrepancies between murine
      models and results obtained using human osteoarthritis tissue. This review
      discusses some recent data regarding the regulation of ADAMTS4 and ADAMTS5 gene
      expression in osteoarthritis, with emphasis on the role of proinflammatory
      cytokines in driving these enzymes, and of the transcription factor NFkappaB in
      mediating their expression.

PMID- 18328164
TI  - Joint hypermobility in Indian children.
AB  - OBJECTIVES: To study the prevalence of joint hypermobility in children from
      Mumbai, India and to study its association with malnutrition. METHODS: In a cross
      sectional field study from September '02 to February '03 in Mumbai, 829 children
      of the lower urban socio-economic strata, between 3 and 19 years of age were
      evaluated independently by two observers for hypermobility using the Beighton 9
      point scoring system. A score of >or= 4/9 was considered positive. Their
      nutritional status was stratified using standard Indian growth charts and
      hypermobility was quantified in various nutritional groups. Musculoskeletal
      symptoms were assessed by a questionnaire given to parents. Standard tests of
      significance (Chi square test, p<0.05-significant) were applied. RESULTS: 58.7%
      of the population studied, had a Beighton score >or= 4/9. There was a declining
      prevalence of joint hypermobility noted with increasing age. Near equal sex
      incidence was noted. A higher incidence of finger signs was noted in comparison
      to elbow hyperextension, knee hyperextension and hands-to-floor. 26% of the
      hypermobile population had musculoskeletal symptoms as compared with 17.2% of the
      non-hypermobile population (p<0.05). A positive Beighton score was found in
      452/734 (61.5%) children with Grade 3 and 4 malnutrition in comparison to 35/95
      (36.8%) children with normal nutrition or mild grades (Grade 1 and 2) of
      malnutrition (p<0.05). In the group with Grade 3 and 4 malnutrition, 26.1% of
      those hypermobile had musculoskeletal symptoms in comparison to 17.7% of their
      non-hypermobile counterparts (p<0.05). CONCLUSIONS: In our study population: 1. A
      high prevalence of hypermobility using Beighton's score was noted; 2. Finger
      signs of the Beighton score were more common than the other signs; 3. Moderate
      and severe malnutrition were associated with hypermobility; 4. Musculoskeletal
      symptoms were linked to joint hypermobility; 5. Moderate and severely
      malnourished hypermobile children were more likely to have musculoskeletal
      symptoms as compared to their non-hypermobile counterparts.

PMID- 18328165
TI  - GSTT1, GSTM1 and GSTP1 polymorphisms and susceptibility to juvenile idiopathic
      arthritis.
AB  - OBJECTIVE: In this study we have analyzed GSTM1, GSTT1 and GSTP1 polymorphisms in
      patients with juvenile idiopathic arthritis (JIA), to investigate a possible role
      of these genes as genetic components of the disease. METHODS: A total of 103
      individuals (49 oligoarticular, 41 polyarticular and 13 systemic) were analyzed
      for the three polymorphisms, using a PCR/RFLP methodology. RESULTS: We have
      observed significantly increased frequencies of individuals with GSTT1 null
      genotype in JIA patients comparing to controls (37% x 21%; p=0.0183). There was a
      2-fold increased risk (OR 2.2, 95% CI 1.2-4.1) associating the disease with the
      GSTT1 null genotype. Considering the subgroups (oligoarticular, polyarticular and
      systemic), the results indicated an association between polyarticular and
      systemic patients and the GSTT1 null genotype. There was a 2-fold increased risk
      for polyarticular patients (OR 2.4, 95%, CI 1.1-5.4), and a 4-fold increased risk
      for systemic patients (OR 4.4, 95%, 1.3-14.5). CONCLUSION: The GSTT1 null
      genotype seems to be involved in polyarticular and systemic JIA.

PMID- 18328166
TI  - Postinflammatory hyperpigmentation (PIH): the presenting sign of systemic lupus
      erythematosus.

PMID- 18328167
TI  - Recurrent pulmonary embolism due to intracardiac thrombi in systemic sclerosis.

PMID- 18328168
TI  - Fibrillary glomerulonephritis in a patient with rheumatoid arthritis.

PMID- 18328169
TI  - Impact of long-term anti-TNF-alpha treatment on insulin resistance in patients
      with rheumatoid arthritis.

PMID- 18328171
TI  - Na+/K+ co-transport in patients with rheumatoid arthritis: an additional risk
      factor for cardiovascular diseases?

PMID- 18328172
TI  - Coeliac disease in 108 patients with juvenile idiopathic arthritis: a 13-year
      follow-up study.

PMID- 18328173
TI  - The c.1298A>C polymorphism in the methylenetetrahydrofolate reductase gene is
      associated with rheumatoid arthritis susceptibility in Italian patients.

PMID- 18328174
TI  - No evidence-based practice by biased information from systematic reviews: the
      case of etanercept and infliximab for the treatment of psoriatic arthritis.

PMID- 18328176
TI  - [The differentiation and regulation of antigen-specific Th17 cells].
AB  - AIM: To assess the differentiation and regulation of antigen specific Th17 cells
      in vitro. METHODS: Naive CD4(+) T cells from OVA-TCR-transgenic mice (OVA-TCR-Tg)
      were isolated and co-cultured with splenocytes from normal BALB/c mice under
      different culture conditions. The expression and production of IL-17 and other
      cytokines were assessed. RESULTS: OVA peptide alone mainly induced Th1 type
      responses. Addition of TGF-beta plus IL-6 induced Th17 response. Furthermore,
      addition of IL-23 to cell culture could promote the differentiation of Th17
      cells. Blocking of IFN-gamma and IL-4 by neutralizing monoclonal antibodies
      enhanced the percentage of IL-17-producing cells. LPS could promote the
      production of Th1 cytokines but had no significant effect on IL-17 expression.
      CONCLUSION: Antigen specific Th17 cells are distinct from antigen specific Th1
      and Th2 cells. TGF-beta, IL-6 and IL-23 are the factors responsible for promoting
      the differentiation and development of Th17 subset, whereas IFN-gamma and IL-4
      have inhibitory effects.

PMID- 18328177
TI  - [Th17 lymphocytes in the peripheral blood of Chinese rhesus macaques (Macaca
      mulatta) with or without SHIV infection].
AB  - AIM: To observe CD4(+)IL-17(+) cells in the peripheral blood of Chinese rhesus
      macaques. METHODS: Peripheral blood samples were collected from normal and SHIV
      infected rhesus macaques. Surface CD3, CD4, CD8 and intracellular IL-17A
      expression of peripheral blood (with or without PMA+Ionomycin stimulation) were
      detected by immunostaining with fluorochrome labeled monoclonal antibodies. The
      samples were acquired with FACScalibur and the data were analyzed with CellQuest.
      RESULTS: IL-17A(+) cells were observed in all the 6 normal rhesus macaques but
      there were very few before cultured with PMA+Ionomycin. About 1.4% of lymphocytes
      were IL-17A(+) cells after stimulation and short-term cultivation, and about 2.7%
      of CD3(+)CD4(+) lymphocytes were IL-17A(+) cells, i.e. CD4(+) Th17 cells. Th17
      cells in the 4 SHIV infected rhesus monkeys were also examined. The number of the
      Th17 cells detected after stimulation and short-term cultivation was not
      significantly different from that of normal monkeys. CONCLUSION: Similar to human
      race, Chinese rhesus macaques possess a subset of CD4(+)IL-17A(+) cells,
      suggesting these rhesus monkey can be used to study the relationship between Th17
      cells and HIV/AIDS.

PMID- 18328178
TI  - [The analysis in the expression of Toll-like receptor 4 mRNA and the effect of
      dexamethasone on mice dendritic cells by real-time PCR].
AB  - AIM: To establish a SYBR Green I quantitative real-time PCR method for detecting
      the expression of the TLR4 mRNA of mice and to monitor the dynamics for TLR4 mRNA
      level of mice bone marrow-derived dendritic cells (DC) in the process of the
      maturation and the effect of dexamethasone (DEX) on TLR4 expression. METHODS: (1)
      DC from mice bone marrow were induced by cytokines and separated by magnetic
      beads. (2) The combined plasmid pUCm-T/TLR4 and pUCm-T/beta-actin for the
      standard materials in the real-time PCR was reconstructed. (3) The dynamics for
      the express TLR4 mRNA of DC cultivated in vitro for 4, 6, 8, 10, 12 days was
      detected respectively. (4) The TLR4 mRNA expression between DC treated with or
      without DEX was detected and compared. RESULTS: (1) The DC with the purity over
      90% were fully separated in success. (2) A SYBR Green I quantitative real-time
      PCR method for analyzing the TLR4 mRNA expression level of the mice was
      successful established. (3) TLR4 mRNA level was stable early during the culture
      of DC and then rise obviously at last. CONCLUSION: There exists a close
      relationship between the level of TLR4 mRNA and the period of maturation of DC
      and the expression of TLR4 could be increased by DEX.

PMID- 18328179
TI  - [Construction and expression of prokaryotic vector encoding extracellular region
      of murine B7-DC].
AB  - AIM: To construct a prokaryotic expression vector for the extracellular domain of
      murine B7-DC(B7-DC(ECD)) gene, and to express the gene in E.coli BL21. METHODS:
      The total RNA was extracted from murine immature bone marrow-derived dendritic
      cells and the extracellular fragment of B7-DC cDNA was amplified by RT-PCR. The
      recombinant plasmid pET32a(+)-B7-DC(ECD) was constructed by cloning the
      extracellular fragment of B7-DC cDNA into the prokaryotic expression vector
      pET32a(+). After the recombinant plasmid was identified by restriction
      endonuclease digestion analysis and DNA sequencing, pET32a(+)-B7-DC(ECD) was
      transformed into E.coli BL21 through IPTG induction to express the target
      protein, and the protein was analyzed by SDS-PAGE and Western blot. RESULTS: A
      582 bp of extracellular fragment B7-DC cDNA was obtained and the sequence was
      confirmed right by DNA sequencing. SDS-PAGE and Western blot analysis showed that
      a protein with molecular weight of 41 000 was expressed in E.coli BL21.
      CONCLUSION: The extracellular fragment of B7-DC is successfully cloned into
      pET32a (+) and expressed in E.coli BL21, which lays a foundation for the further
      functional research of B7-DC.

PMID- 18328180
TI  - [Effect of anisomycin on allogeneic skin transplantation in mice].
AB  - AIM: To investigate the effect of anisomycin on the reactivity of lymphocytes and
      the rejection in the skin transplantation in mice. METHODS: The reactivity of T
      cells in unilateral or bilateral mixed lymphocyte reaction was detected by MTT
      assay. The skins from C57BL/6 mice were transplanted to BALB/c mice and the
      survival period of the grafts was assessed. The recipients were divided into
      three groups (physiological saline group, cyclosporin A group and anisomycin
      group). They were injected with physiological saline (0.1 mL), cyclosporin A (20
      mg/kg) and anisomycin (12.5 mg/kg) separately once a day for 3 days before the
      operation and 7 days after the operation. RESULTS: With the optimal dose of 10.0
      microg/L, anisomycin inhibited the reactivity of lymphocyte cells in both
      unilateral and bilateral mixed lymphocyte reactions. The survival period of the
      grafts from anisomycin group was longer than that from cyclosporin A group and
      physiological saline group. CONCLUSION: Anisomycin can inhibit the reaction of
      lymphocytes and prolong the survival period of the grafts in skin transplantation
      effectively. It could be used as a new way for transplantation rejection
      treatment.

PMID- 18328181
TI  - [Construction of a fusion gene expression vector containing mouse Ipr1 and EGFP
      and its expression in murine macrophage].
AB  - AIM: To construct an eukaryotic expression vector containing the fusion gene of
      mouse Ipr1 and EGFP and to study its expression in murine macrophage RAW264.7.
      METHODS: The coding sequence of Ipr1 gene was amplified from the total RNA of
      C57BL/6J mouse thymus by RT-PCR. The gene was cloned into pEGFP-C1 and the
      recombinant plasmid was identified by PCR, restrict endonuclease digestion and
      sequencing. Then the pEGFP-Ipr1 was transiently transfected into RAW264.7. The
      expression of Ipr1 gene and fusion protein was detected by RT-PCR and laser
      scanning confocal microscopy. RESULTS: The whole coding sequence of Ipr1 was
      successfully amplified. The recombinant plasmid was identified by PCR, restrict
      endonuclease digestion and sequencing. The fusion protein was successfully
      expressed in the targeted cells and its localization was in nucleus. CONCLUSION:
      The eukaryotic expression vector pEGFP-Ipr1 has been successfully constructed.
      The fusion protein can be expressed in murine macrophage RAW264.7 and located in
      nucleus.

PMID- 18328182
TI  - [IFN-gamma promotes human monocytes to differentiate to untypical mature DC].
AB  - AIM: To explore the morphologic and phenotypic changes of monocytess in response
      to the stimulation of IFN-gamma, TNF-alpha and IFN-alpha. METHODS: Newly isolated
      monocytes from human PBMCs were treated with IFN-gamma, TNF-alpha or IFN-alpha.
      The phenotypic growth of monocytes with or without stimulation was observed by
      microscope. The surface expression of CD1a, CD14, CD80, CD83, CD86, and HLA-DR on
      the monocytes was assayed by flow cytometry. RESULTS: After IFN-gamma
      stimulation, monocytes displayed the shape of fusiform or polygon and were more
      likely to adhere and cluster to form the distinct structure as "cell islet". IFN
      gamma; also induced or up-regulated the surface expression of CD80, CD83, CD86,
      and HLA-DR on the monocytes and down-regulated the CD14 expression. IFN-gamma
      even induced the CD1a expression and changed the monocytes phenotype from
      CD14(+)CD1a(-)CD83(-) to CD14(+)CD1a(+)CD83(+) after stimulated for 5 days.
      Cytokines TNF-alpha and IFN-alpha; have the different impacts on monocytes from
      IFN-gamma. CONCLUSION: IFN-gamma have the immunoregulatory function of making
      monocytes differentiate to untypical mature dendritic cells (DC).

PMID- 18328183
TI  - [Perparation and characterization of the monoclonal antibodies against
      listeriolysin O].
AB  - AIM: To prepare the monoclonal antibodies (mAbs) against listeriolysin O (LLO),
      which is the major virulence factor of Listeria monocytogenes. METHODS: The
      BALB/c mice were immunized with the SDS-PAGE product of BL21(pGEX-6p-1-hly). The
      purified LLO-GST protein was used as antigen for detection. mAbs against LLO were
      prepared by using the lymphocyte hybridoma technique. The specificity of mAbs was
      characterized by Dot-ELISA and Western blot. RESULTS: Three hybridoma cell lines
      named 3B6, 4D1 and 5D10 secreting mAbs against LLO were obtained. The
      immunoglobulin subclasses of the mAbs were IgG1. The ELISA titer of the ascitic
      fluids of 3B6, 4D1 and 5D10 was 1:200,000, 1:200,000 and 1:100,000, respectively.
      Western blot analysis confirmed the three mAbs reacted on fusion protein LLO-GST
      but didn't react on protein GST. Dot-ELISA proved the three mAbs only react on
      the bacteria expressing LLO. CONCLUSION: The successful preparation of three mAbs
      specific to protein LLO lays a foundation for further study of the biological
      characteristics of LLO and the pathogenesis of Listeria monocytogenes.

PMID- 18328184
TI  - [Prokaryotic expression of human GITRaa27-165 and preparation of its polyclonal
      antibody].
AB  - AIM: To express and purify the extracellular region of human glucocorticoid
      induced tumor necrosis factor (hGITR(aa27-165)), and to prepare and identify the
      polyclonal antibody (pAb) against this fusion protein. METHODS: The 429 bp DNA
      sequence of hGITR(aa27-165) was obtained from pGEM T-hGITR by PCR and then it was
      inserted into pQE30 plasmid to construct the prokaryotic expression plasmid pQE30
      hGITR(aa27-165). pQE30-hGITR(aa27-165) was transformed into E.coli. The target
      fusion protein was expressed with the induction of Isopropyl beta-D-1-thiogalacto
      pyranoside (IPTG) and purified by Ni(2+)-NTA affinity chromatography column. The
      antiserum against hGITR(aa27-165) was obtained from the rabbits immunized with
      hGITR(aa27-165). The titer of pAb was detected by ELISA and the specificity of
      pAb was identified by Western blot. RESULTS: The prokaryotic expression plasmid
      pQE30-GITR(aa27-165) was constructed successfully. The culture condition in which
      the target fusion protein was highly expressed was found out: the optimal
      concentration of IPTG was 0.5 mmol/L, the culture temperature was 30 degree
      centigrade and the culture time was 6 h. The GITR(aa27-165) fusion protein was
      effectively expressed in E.coli as inclusion body. Soluble protein was obtained
      through denaturation and refolding procedure. The fusion protein was purified by
      Profinity IMAC Ni-Charged Resin affinity column with above 90% purity. The anti
      GITR(aa27-165) pAb was prepared by immunizing the rabbits with the purified
      target fusion protein. ELISA showed the titer of pAb was 1:1.6 x 10(5). Western
      blot analysis confirmed anti-GITR(aa27-165) pAb was of good specificity.
      CONCLUSION: The fusion protein hGITR(aa27-165) with high purity has been obtained
      and the anti-hGITR(aa27-165) pAb with high titer and good specificity has been
      prepared. Our study may be conductive to further research into the molecular
      mechanism of action between human GITR and GITRL.

PMID- 18328185
TI  - [Preparation and characterization of the rabbit polyclonal antibody against the
      alpha3 domain of human CD1d].
AB  - AIM: To prepare the rabbit antibody against the alpha3 domain of the human CD1d
      (hCD1d-alpha3). METHODS: The gene fragment coding for hCD1d-alpha3 was amplified
      by PCR and cloned into prokaryotic expression vector pET28, then expressed in
      E.coli BL21(DE3). The recombinant protein hCD1d-alpha3 was purified with Ni(2+)
      NTA agarose column and used as immunogen to immunize the rabbit. The titer and
      specificity of the anti-hCD1d-alpha3 antibody from the rabbit were analyzed by
      ELISA, Western blot and immunohistochemistry, respectively. RESULTS: The
      recombinant hCD1d-alpha3 was successfully expressed and purified, and the
      polyclonal anit-hCD1d-alpha3 antibody was successfully prepared. The titer of the
      antiserum was 1:6 400 by ELISA. Western blot analysis showed this antiboday
      reacted specifically with hCD1d. Immunohistochemistry analysis showed the
      antibody could recognize the native hCD1d in the human intestinal tissue.
      CONCLUSION: The anti-CD1d-alpha3 antibody from the rabbit with high titer and
      specificity has been prepared with purified recombinant hCD1d-alpha3 as
      immunogen, which lays a foundation for further research into detection and
      functional study of CD1d.

PMID- 18328186
TI  - [Prokaryotic expression, purification, and polyclonal antibody generation of beta
      subunit of human F1F0-ATP synthase].
AB  - AIM: To express and purify the beta subunit of human F1F0-ATP synthase (hATP5B)
      in prokaryotic system, and generate its polyclonal antibody in rabbits. METHODS:
      The coding sequence of hATP5B mature peptide was amplified by RT-PCR from human
      umbilical vein endothelial cells (HUVEC) and then cloned into prokaryotic
      expression vector pET28a(+). The plasmid was transformed into E.coli BL21(DE3) to
      express hATP5B in reponse to IPTG induction. Expressed protein was purified by
      Ni(2+) metal-chelating chromatograph, and refolded by dialysis. The products were
      analyzed by SDS-PAGE and Western blot. Refolded protein was injected into rabbits
      to generate polyclonal antibody. The titer of the polyclonal antibody was
      determined by indirect ELISA. The specificity and the binding ability were
      detected by Western blot and cell immunofluorescence analysis. RESULTS: DNA
      sequencing confirmed that the coding sequence of hATP5B mature peptide was
      completely concordant with the original sequence (NM_001686, hATP5B's GenBank
      accession number). SDS-PAGE showed that the relative molecular masses (M(r)) of
      the expressed, purified, and refolded products were about relative molecular
      masses M(r) 55,000, which was in accordance with the predicted. Grayscale
      scanning showed that the expressed recombinant hATP5B (rhATP5B) accounted for
      36.8% of the total bacteria protein, and the purity of purified product was
      98.3%, of refolded 99.1%. The result of Western blot is positive. The titer of
      the polyclonal antibody was 1:640,000, and it specifically recognized the native
      antigen in HUVEC. CONCLUSION: hATP5B expressed in prokaryotic system has strong
      immunogenicity, and the polyclonal antibody with high titer and specificity was
      obtained from immunization of rabbits. The high level prokaryotic expression of
      hATP5B and the preparation of its antibody lay the foundation for further
      function research of hATP5B.

PMID- 18328187
TI  - [Selection and characterization of human scFv antibodies against hepatocellular
      carcinoma].
AB  - AIM: To construct a fully human anti-hepatoma single-chain phage antibody
      library, select the anti-hepatoma scFv from it and identify its characteristics.
      METHODS: A fully human scFv-displaying phage library was constructed by using
      phage antibody library technique in combination with in vitro immunization and
      EBV transformation. The library was subjected to three rounds of positive and
      negative cell panning and enrichment and then it was selected by ELISA. The
      binding specificity of phage antibodies with hepatoma carcinoma cells was
      confirmed by immunohistochemistry. RESULTS: After scFv genes being cloned into
      vector Fuse5 and transformed into E.coli MC1061 via electroporation, a phage
      antibody library containing 1.0 x 10(8) TU (transduced unit) was obtained through
      tetracycline-resistant screening. After panning, enrichment and testing by ELISA,
      3 phage antibody clones reacting more strongly to HepG(2) than QSG-7701 were
      picked out of 2798 clones. One clone, SA3, was further analysed after DNA
      sequencing. The results of immunohistochemistry with cultured cells were similar
      to those of ELISA. SA3 reacted specifically to hepatoma cells in most human
      hepatoma tissue sections but in few human normal liver tissue sections. The
      distinction of positive rates is of a great statistical significance. CONCLUSION:
      A fully human anti-hepatoma scFv fusion phage library has been constructed. ELISA
      and immunohistochemistry results conform SA3 specifically bind with hepatoma
      carcinoma cells. The scFv fragment against hepatoma may be further developed and
      applied in clinical diagnosis and therapy of liver cancer.

PMID- 18328188
TI  - [Secretable eukaryotic expression of recombinant chicken Iglambda and preparation
      of monoclonal antibodies against chicken Iglambda].
AB  - AIM: To construct the eukaryotic expression vector for chicken Iglambda light
      chain, to express it on COS7 cells and to prepare the monoclonal antibodies
      against chicken Iglambda. METHODS: The cDNA of chicken Iglambda light chain with
      signal peptide sequence was amplified and then inserted into eukaryotic
      expression plasmid pcDNA3 after double enzyme cutting. The constructed
      recombinant vector was transfected into COS7 cells by lipofectamin and the
      secretable eukaryotic expression of chicken Iglambda light chain was verified by
      Western blot. The monoclonal antibodies (mAbs) against chicken Iglambda light
      chain were prepared by immunizing BALB/c mice with 2 x 10(6) chicken B cells and
      by cell fusion technology. RESULTS: The eukaryotic expression vector was
      successfully constructed. Western blot demonstrated that chicken Iglambda light
      chain existed in the cultural supernatant. The hybridoma lines secreting anti
      Iglambda mAbs were screened by indirect ELISA. The specific reactivity between
      anti-Iglambda mAbs and recombinant chicken Iglambda light chain was detected by
      Western blot. CONCLUSION: The secreted recombinant chicken Iglambda light chain
      and anti-Iglambda mAbs provide a basis for further study of the functions of
      chicken Iglambda.

PMID- 18328189
TI  - [Expression and immunity of fused protein H1N1 M2e and cholera toxin B].
AB  - AIM: To construct the eukaryotic recombinant plasmid pcDNA3.1a(+)-M2e/CtB which
      contains H1N1 M2e gene and cholera toxin B subunit gene (CtB) and to study the
      expression and immunity of recombinant protein M2e/CTB in NIH3T3 cells. METHODS:
      M2e/CtB gene was cloned by PCR and digested with Hind III and Xho I. M2e/CtB was
      linked into pcDNA3.1a(+) to build eukaryotic expression plasmid pcDNA3.1a(+)
      M2e/CtB. The pcDNA3.1a(+)-M2e/CtB was transfered into competent E.coli JM109. The
      transformed colonies were verified by Hind III and Xho I, PCR, and sequencing.
      The NIH3T3 cells were transfected with pcDNA3.1a(+)-M2e/CtB by positive ion
      polymer. The product of M2e/CtB gene with stable expression was analysed by
      immunofluorescence, RT-PCR sequencing, and Western blot. RESULTS: The digested
      pcDNA3.1a (+)-M2e/CtB contains correct M2e and CtB gene. Blastn results showed
      the genetic homongenicity of M2e and CtB were 100%, respectively. The
      pcDNA3.1a(+)-M2e/CtB efficiently expressed M2e/CTB protein in the eukaryotic
      NIH3T3 cells. The cell lysis and supernant both contained the M2e/CTB protein,
      which had the immunity and reactivity to both anti-M2e and anti-CTB. The relative
      molecular mass of M2e/CTB protein was about 18 000 analysed by Western blot.
      CONCLUSION: A new recombinant eukaryotic plasmid pcDNA3.1a(+)- M2e/CtB has been
      successfully constructed. The plasmid can express the fused protein of M2e with
      CTB. Our study will help further research into new and effective DNA vaccines
      against influenza virus A.

PMID- 18328190
TI  - [Inhibitory effect of anti-Lewis y antibody on alpha1,2-fucosyltransferase gene
      transfected human ovarian cancer cells in vitro].
AB  - AIM: To study the inhibitory effect of anti-Lewis y monoclonal antibody on
      proliferation, adhesion and invasion of alpha1, 2-fucosyltransferase gene
      transfected human ovarian cancer cell line RMG-I-H with over-expression of Lewis
      y antigen in vitro. METHODS: The changes of proliferation, adhesion and invasion
      of RMG-I-H cells in vitro were detected by cell growth assay, cell adhesive assay
      and cell invasive assay, respectively, with goat anti-human IgG antibody treated
      group or non-antibody treated group as control. RESULTS: The proliferation and
      adhesion of RMG-I-H cells were remarkably inhibited by preincubation of the tumor
      cells with anti-Lewis y antibody in vitro (P<0.05). The growth inhibitory rate
      from the second day to the seventh day was 5.62%, 19.75%, 34.96%, 46.51%, 49.78%
      and 33.33%, respectively. The adhesion inhibitory rate at different time points
      (15, 30, 60 min) was 47.59%, 58.64% and 13.85%, respectively. Invasive assay with
      a transwell cell culture chamber showed that there were no significant
      differences of invasion in vitro between each concentration of the Lewis y
      antibody treated group and non-antibody treated group (P>0.05). CONCLUSION: Anti
      Lewis y antibody significantly inhibits the proliferation and adhesion of RMG-I-H
      cells cultured in vitro, but it has no effect on invasion, which indicates that
      Lewis y is associated with some biological behaviors, such as proliferation and
      adhesion. The antibody against Lewis y may be an effective anti-metastasis agent
      for the treatment of patients with ovarian cancer.

PMID- 18328191
TI  - [Significance and effect of Glucosidorum Tripterygii tororum on expressions of
      Foxp3 in regulatory T cells in type 1 diabetic rat model].
AB  - AIM: To investigate the significance and effect of Glucosidorum Tripterygii
      tororum (GTT) on the expressions of Foxp3 in CD4(+)CD25(+) regulatory T cells
      (Tr) in type 1 diabetic rat model. METHODS: 48 rats were divided evenly into 3
      groups by random. Diabetic model was developed by multiple low dose
      intraperitoneal injection of streptozotocin in group II, III, and group I was
      treated as normal control. After the establishment of the model, administration
      of GTT was conducted in group III, which was performed once a day, lasting three
      monthes. Lymphocyte proliferation was detected by lymphocyte transformation test
      (MTT assay). The expression of Foxp3 mRNA was measured in peripheral blood and
      spleen by using real-time PCR. The expression of Foxp3 protein in lymphoid node
      and spleen was detected by immunohistochemistry. RESULTS: The blood glucose level
      in group II, III was obviously higher than that of control group (P<0.01),
      followed with lymphocyte infiltrating in pancreatic islets. The infiltrating
      degree in group III was decreased than that of group II. The proliferation of
      splenic lymphocyte in group II, III was evidently increased comparing with the
      control group (P<0.01). After administration of GTT, the proliferation in group
      III was lower than that in group II. In group II, III, the expressions of Foxp3
      mRNA and protein increased markedly compared with control group (P<0.05).
      Moreover, the level in group III was especially enhanced, but compared with group
      II, there was no significantly difference (P>0.05). CONCLUSION: Foxp3(+) Tr may
      involve in the pathogenesy of type 1 diabetes indused by STZ. GTT did have
      therapeutical effect on type 1 diabetes, possibly through upregulating the
      expressions of Foxp3 in Tr.

PMID- 18328192
TI  - [The killing effect and bystander effect of linamarase/linamarin suicide gene
      system on human hepatocellular carcinoma cell line HepG2 in vitro].
AB  - AIM: To investigate the killing effect of linamarase/linamarin (lis/lin) system
      on hepatocellular carcinoma cell line HepG2 in vitro. METHODS: A cDNA library was
      built from RNA of cassava by RT-PCR, then the linamarase gene was amplified from
      it by PCR and cloned into the eukaryotic expression vector plasmid pEGFP-N1,
      which made up the recombinant plasmid pEGFP-N1-lis. The human HCC cells HepG2
      were transfected with the recombinant plasmid mediated by electroporation and
      screened by G418 to yield the positive clone which was termed HepG2/lis. The
      expression of lis was confirmed by fluorescent staining, RT-PCR and Western blot.
      The killing effect and bystander effect of linamarin with different
      concentrations on HepG2 was detected by MTT. RESULTS: RT-PCR confirmed the
      expression of lis gene in HepG2 and Western blot analysis confirmed existence of
      lis-EGFP fusion protein in HepG2. Linamarin in low concentration had shown
      notable cytotoxic effect on HepG2/lis. When HepG2/lis cells were mixed with
      parental HepG2 cells at a ratio of 10:90 and cultivated in 500 mg/L lin medium,
      significant bystander effect was observed in vitro. CONCLUSION: The
      linamarase/linamarin suicide gene system has strong killing effect and bystander
      effect on HCCs with the concentration of 500 mg/L lin.

PMID- 18328193
TI  - [Adenovirus mediated targeted genetherapy of Staphylococcal enterotoxin A and
      CD80 for hepatoma and its primary immune mechanisms].
AB  - AIM: To observe the effects of hepatoma-targeting recombinant adenovirus vectors
      of staphylococcal enterotoxin A (SEA) and/or CD80 gene on hepatoma and to study
      its immunological mechanisms. METHODS: Using AdEasy adenovirus system, we
      constructed recombinant adenovirus vectors of SEA and/or CD80 gene driven by
      alpha-fetoprotein (AFP) enhancer I and promoter. After intratumoral therapy for
      the mice bearing subcutaneous xenograft hepatoma with the recombinant
      adenoviruses, SEA and/or CD80 mRNA and protein were detected by RT-PCR and
      Western blot. IFN-gamma-producing cell frequency and specific cytotoxicity of T
      lymphocytes to Hepa1-6 cells were detected by ELISpot and LDH-released assay in
      the splenocytes. Effects of recombinant adenoviruses on hepatoma were assessed by
      changes of tumor volumes and survival time in the treated mice. RESULTS: The
      recombinant adenoviruses constructed by us made SEA and/or CD80 mRNA and protein
      targetedly express in hepatoma tissues. When compared with the empty vector and
      PBS groups, the IFN-gamma-producing cell frequency and specific cytotoxicity of T
      lymphocytes increased, the tumor volumes of mice decreased and the survival time
      increased in the double-gene and single-gene groups. Double genes elicited better
      antitumor effects and stronger immune responses. There were no significant
      differences in the effects between CD80 group and SEA group or between empty
      vector group and PBS group. CONCLUSION: The hepatoma-targeting recombinant
      adenovirus vectors constructed in this study can elicit effective antitumor
      effects on hepatoma and the effects of double genes are better than that of
      single gene.

PMID- 18328194
TI  - [Association of cytotoxic T lymphocyte antigen-4 gene polymorphisms with
      susceptibility to breast cancer].
AB  - AIM: To investigate the association between the CTLA-4 promoter-1722(T/C) and 3'
      untranslated region CT60(G/A) polymorphisms and the risk of breast cancer in Han
      women of northeast China. METHODS: 328 patients with breast cancer and 327
      healthy people as control were genotyped for -1722 and CT60 polymorphism using
      polymerase chain reaction and restriction fragment length polymorphism. RESULTS:
      The frequency of the G allele at the CT60 site in breast cancer patients was
      statistically higher than that in control(28.7% vs 23.5%, P=0.0352, OR=1.30, 95%
      CI=1.02-1.67). The frequency of -1722C-CT60A haplotype in control was
      significantly higher than that in breast cancer patients(P=0.0283, OR=0.77, 95%
      CI=0.97-0.61). However, the distribution of genotypes at -1722 site was not
      significantly different between breast cancer patients and control. CONCLUSION:
      The polymorphism of -1722T/C and CT60G/A may be related to the development of
      breast cancer in Han women of northern China.

PMID- 18328195
TI  - Tazarotene 0.1 percent cream plus clindamycin 1 percent gel versus tretinoin
      0.025 percent gel plus clindamycin 1 percent gel in the treatment of facial acne
      vulgaris.
AB  - Topical retinoids are the cornerstone of therapy for acne vulgaris. Nevertheless,
      the adjunctive use of other anti-acne agents can help enhance the efficacy of
      topical retinoids still further. Given that tazarotene 0.1 percent gel has
      previously shown significantly greater efficacy than tretinoin 0.025 percent gel,
      it is likely that tazarotene plus clindamycin offers superior efficacy to
      tretinoin plus clindamycin, which has recently become available as a combination
      product. A total of 150 patients with facial acne vulgaris were randomly assigned
      to receive either tazarotene 0.1 percent cream plus clindamycin 1 percent gel, or
      tretinoin 0.025 percent gel plus clindamycin 1 percent gel. Each medication was
      applied once daily in the evening (clindamycin followed by the retinoid 5-10
      minutes later) for up to 12 weeks. At week 12, the reduction from baseline in
      lesion counts was greater with tazarotene/clindamycin than tretinoin/clindamycin
      for both the non-inflammatory lesion count (71% vs. 52%, p< or =.01) and the
      inflammatory lesion count (77% vs. 67%, P=.053). Tazarotene/clindamycin also
      resulted in a significantly higher incidence of patients achieving > or = 50
      percent global improvement (incidence of 88% vs. 75% at week 12; p< or =.05).
      Both regimens were similarly well tolerated. In the treatment of facial acne
      vulgaris, tazarotene plus clindamycin offers significantly greater efficacy than
      tretinoin plus clindamycin and has comparable tolerability.

PMID- 18328196
TI  - Using cellphones for teledermatology, a preliminary study.
AB  - We compared live and instantaneous digital image examination of hospitalized
      dermatology consultation patients and to assess the reliability and the
      practicality of a teledermatology system equipped with the cellular phone
      cameras. A dermatology resident examined ten hospitalized dermatology
      consultation patients. Then a medical student took digital pictures of these
      lesions from consenting patients with a cell phone camera. The pictures were
      forwarded to a supervising dermatologist who was able to review them using the
      identical phone. The differential diagnoses given by the resident and the
      supervising dermatologist were recorded. Identifiable facial images were never
      taken. The concordance of the diagnoses between resident and off site attending
      was 80 percent (8/10 cases) when a diagnosis could be made remotely. In one case
      no diagnosis could be made because of poor photographic quality and small screen
      and in one case the attending diagnosis was incorrect. The practicality of this
      cellular phone camera teledermatology system depended on the Sprint wireless
      network, which was sometimes unreliable. Cellular phones with cameras offer a
      means to deliver bedside supervision of dermatology residents but transmission
      issues, small screen size, and photographic quality complicate their use.

PMID- 18328197
TI  - Ranking the dermatology programs based on measurements of academic achievement.
AB  - BACKGROUND: The only dermatology rankings in the past were based on National
      Institutes of Health (NIH) funding and journal citations. OBJECTIVE: To determine
      the highest ranking academic dermatology programs based on 5 outcome measures and
      on an overall ranking scale. To the best of our knowledge, this is the first
      report to rank the dermatology programs on 4 of the following outcome measures of
      academic achievement and with an overall ranking. METHODS: We collected extensive
      2001 to 2004 data ranging from total publications to grant funding on 107 U.S.
      dermatology programs and their full-time faculty. Data from part-time and
      volunteer faculty were not used. MAIN OUTCOME MEASURES: Publications in 2001 to
      2004; NIH funding in 2004; Dermatology Foundation grants in 2001 to 2004; faculty
      lectures in 2004 delivered at national conferences; number of full-time faculty
      members who were on the editorial boards of the top 3 U.S. dermatology journals
      and the top 4 subspecialty journals RESULTS: We used the 5 outcome measures to
      tabulate the highest ranking programs in each category. Using a weighted ranking
      system, we also tabulated the overall top 30 dermatology programs based on these
      5 outcome measures. LIMITATIONS: We were not able to determine the total amount
      of NIH funding in dollars of the dermatology divisions. The impact factors of the
      journal in which these publications appeared was not factored into our
      calculations. Since faculty members may collaborate on the same publication, some
      publications may have been double-counted. CONCLUSION: In descending order, the 5
      highest ranked academic programs are the University of Pennsylvania; University
      of California, San Francisco; Yale-New Haven Medical Center; New York University;
      and University of Michigan. This ranking system may allow residents and faculty
      to improve the academic achievements at their respective programs.

PMID- 18328198
TI  - Compared therapeutic efficacy between intralesional bleomycin and cryotherapy for
      common warts: a randomized clinical trial.
AB  - In spite of many available studies on bleomycin and cryotherapy in treating
      warts, little head to head research is done to compare efficacy of these
      treatments. Our aim was to compare the therapeutic effects of intralesional
      bleomycin and cryotherapy on common warts of the hands and feet. In this clinical
      trial 44 patients above 12 years of age referred to the dermatology clinic of
      Bouali University Hospital were enrolled. The patients were required to have
      warts on at least two symmetric limbs (hands or feet). The warts located on right
      and left limbs of each patient were examined and counted. Each patient received
      both cryotherapy and intralesional bleomycin on his or her warts. The two
      treatment types were randomly allocated to either right sided or left sided
      warts. Each patient was evaluated at 2 week intervals and retreated if necessary
      up to three times. Data were analyzed by SPSS 11 and EPI Info 2002 statistical
      packages. The mean number of warts was 5.2 on upper limbs and 4.6 on lower limbs.
      In 86.4 percent of the cases all warts on the limb side treated by intralesional
      bleomycin were cleared compared with 68.2 % for cryotherapy (P<0.05). Relative
      risk for the effect of bleomycin compared to cryotherapy in this regard was 1.27
      (1<RR<1.6). We found bleomycin to have a clearance rate equal to 87.6 percent of
      warts, compared to 72.3 percent by cryotherapy. Relative risk for therapeutic
      effect of bleomycin compared to cryotherapy in this regard was 1.23
      (1.11<RR<1.33). CONCLUSION: Intralesional bleomycin is more effective than
      cryotherapy in treating warts on hands and feet.

PMID- 18328199
TI  - Minimizing discomfort during the injection of Radiesse with the use of either
      local anesthetic or ice.
AB  - Radiesse or calcium hydroxylapatite has been used for years in patients with HIV
      associated lipoatrophy as well as for facial wrinkles and nasolabial folds [2,
      3], but can be painful to inject especially in the latter area. This discomfort
      can be severe enough that after an injection with Radiesse, a patient, despite
      excellent results, may refuse additional treatments. We hereby describe several
      methods of minimizing discomfort during Radiesse injections of nasolabial folds
      and other facial areas.

PMID- 18328200
TI  - Modified Bier block anesthetic technique is safe for office use for botulinum a
      toxin treatment of palmar and plantar hyperhidrosis.

PMID- 18328201
TI  - Alternative uses of a curette.

PMID- 18328202
TI  - A hairy development in hypertrichosis: a brief review of Ambras syndrome.
AB  - Ambras syndrome was described less than 20 years ago. The initial report focused
      on the subtle, but important distinguishing characteristics that separate this
      from other forms of congenital hypertrichosis. This review, we examine this
      fascinating syndrome, and the current scientific perspectives in discussion. This
      review will help increase and expand our knowledge base of this uncommon
      syndrome, and should encourage future dermatologic analysis and reports on Ambras
      syndrome.

PMID- 18328203
TI  - Keloids: pathophysiology and management.
AB  - Keloid formation occurs as a result of abnormal wound healing. Despite the high
      prevalence of keloids in the general population, they remain one of the more
      challenging dermatologic conditions to manage. More than a cosmetic nuisance,
      they are often symptomatic and can have a significant psychosocial burden for the
      patient. Although multiple treatment modalities exist, no single treatment has
      proven widely effective. In fact, recurrence following treatment is generally the
      norm. Combination therapy is likely the optimal strategy. In this review, we
      highlight the clinical features, pathophysiology and management of keloids.

PMID- 18328204
TI  - A review of DNA repair and possible DNA-repair adjuvants and selected natural
      anti-oxidants.
AB  - Few other organs have the environmental exposure-neoplasia relationship that has
      been observed between epithelial cutaneous malignancy and UVB exposure. A
      significant DNA type of defective linking of DNA nucleotides involves pyrimidine
      dimers. Important insight into the molecular processes that affect the response
      of cells to UVB have been provided by the study of rare inherited diseases
      characterized by DNA repair defects. Nucleotide excision repair is the best
      characterized of these and its importance is illustrated by the disease,
      xeroderma pigmentosum. This heterogenous disorder clinically characterized by
      malignant tumor development and molecularly by distinct alterations in the
      nucleotide excision repair apparatus. More recently, other DNA mechanisms have
      been shown to have some role in skin cancer, such as DNA-mismatch repair and
      double-stranded DNA breaks. Herein, we discuss the DNA-repair adjuvants a aqueous
      extract of Urcaria tomentosa (AC-11, Optigenex, Inc.), and T4 endonuclease V that
      is prepared in a liposome lotion (Dimericine, Applied Genetics Inc. Dermatics).
      The positive effects on the integrity DNA of other substances (from nature, heat
      shock proteins and cytokines) including IL-12, Polypodium leucotomos, and
      ubiquitin are also reviewed. Understanding DNA repair mechanisms is far from
      complete; further understanding will provide insight into the pathogenesis of
      cancer and pave the way for efficacious therapeutic agents.

PMID- 18328205
TI  - Acrodermatitis enteropathica.
AB  - A 13-year-old girl presented with a history of red scaly plaques involving the
      chest, arms and legs beginning in infancy. Punch biopsy revealed psoriasiform
      hyperplasia and pallor of the epidermis. The patient's serum zinc level was 36
      mug/dl [nl. 66-144 mug/dl]. A diagnosis of acrodermatitis enteropathica was
      established and the patient responded well to zinc replacement therapy.
      Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by
      mutations in SLC39A4, which encodes the tissue-specific zinc transporter ZIP4.

PMID- 18328206
TI  - Lupus vulgaris of the popliteal fossa: a delayed diagnosis.
AB  - Lupus vulgaris (LV) is the most common form of cutaneous tuberculosis. It
      commonly presents on the head and neck regions. The diagnosis may be difficult
      when LV occurs at unexpected regions or in unusual clinical forms. Sometimes
      special stains for the organism and mycobacterial cultures may be negative.
      Nevertheless, it is usually possible to reach the correct diagnosis of LV using
      clinical and histopathological findings. But at times, a therapeutic trial with
      antitubercular agents may be required.

PMID- 18328207
TI  - Unilateral laterothoracic exanthema with coincident evidence of Epstein Barr
      virus reactivation: exploration of a possible link.
AB  - Unilateral laterothoracic exanthem (ULE) was first described in 1962 in the
      United States and comprehensively elaborated in 1992. Although ULE most commonly
      occurs in children, ULE can occur in adults. ULE may or may not be preceded by a
      viral prodrome and is marked by coalescing erythematous papules predominately on
      one side of the body. ULE usually lasts 4-6 weeks but can last as little as 2
      weeks. It has inconsistently been linked to viral infection, in particular
      parvovirus B-19. I note ULE in an adult with concurrent reactivation of Epstein
      Barr virus (EBV) that lasted 4 weeks. The role of the reactivation of EBV in
      human disease and ULE is explored.

PMID- 18328208
TI  - Successful long-term management of refractory cutaneous and upper airway
      sarcoidosis with periodic infliximab infusion.
AB  - A clinically refractory case of cutaneous sarcoidosis was successfully treated
      with infliximab infusion therapy at a dose of 5mg/kg. Skin lesions cleared
      dramatically and remain resolved during a 3(1/2) year follow-up, the longest
      follow-up reported to date. Ongoing biological drug therapy has been administered
      at a frequency of every 8-10 weeks. Despite cost and safety concerns, infliximab
      should be considered in cases of cutaneous sarcoidosis refractory to standard
      treatment protocols.

PMID- 18328209
TI  - Treatment of molluscum contagiosum: a brief review and discussion of a case
      successfully treated with adapelene.
AB  - Molluscum contagiosum occur in 2-8 percent of children. This infection is among
      the most common viral skin infections in children. Although the lesions will
      resolve spontaneously when puberty, there are several reasons to treat them. The
      lesions can be cosmetically unappealing. About 10 percent of those with this
      infection develop a pruritic eczematous eruption. In about 4 percent of children
      with molluscum, the lesions are numerous and recurrent with no other coexisting
      immunological problem. Patients who have atopic dermatitis may develop widespread
      involvement with molluscum. Treatment options include destruction, topical
      therapy, and oral therapy. Destructive treatment modalities include curettage,
      cryotherapy, expression or pricking with a sterile needle, electrodesiccation,
      photodynamic therapy, and laser ablation. Destructive therapy is poorly tolerated
      in children. Topical medical therapy includes salicylic acid, glycolic acid,
      tretinoin, tazortene, 5 percent sodium nitrite co-applied daily with 5 percent
      salicylic acid topical preparations, podofilox, liquefied phenol, tretinoin,
      cantharidin, and potassium hydroxide. Oral treatment of molluscum includes
      cimetidine. No therapy is universally effective. I report herein a case of
      generalized numerous and recurrent molluscum treated with minimal irritation with
      adapelene.

PMID- 18328210
TI  - Bilateral facial pigmentation.
AB  - A 38-year-old man presented with a chief complaint of blue-speckled secretions on
      his cheeks, brought on by exertion. Based on the clinical features, a diagnosis
      of apocrine chromhidrosis was made. Histopathologic exam further supported this
      diagnosis. Possible treatment options for apocrine chromhidrosis are discussed.

PMID- 18328211
TI  - An infant with bullous pemphigoid.
AB  - Bullous pemphigoid is the most common subepidermal autoimmune blistering disease.
      However, it is very rare in the pediatric population. A 5-month-old male infant
      presented with multiple bullae located on palms and soles. Complete blood count
      revealed relative eosinophilia . A biopsy revealed a subepidermal blister present
      along with a dermal mononuclear infiltrate rich in eosinophils. In focal areas
      collagen flame figures, were also observed. Direct immunofluorescence showed
      linear reactivity for C3c and IgG at the dermal-epidermal junction. IgA was not
      found. Complete resolution was achieved after oral deflazacort (1.5mg/kg/day)
      with progressive dose reduction over 2 weeks. Bullous pemphigoid is extremely
      rare in the infant. In our case the disease presented with an unusual localized
      (acral) clinical distribution and a favorable outcome.

PMID- 18328212
TI  - Scaly scalp associated with crusted scabies: case series.
AB  - The diagnosis of crusted scabies is becoming more relevant due to the increase in
      number of immunocompromised patients. To date, more than 200 cases have been
      reported in the literature. However, crusted scabies seems to be under-diagnosed
      because of its unusual presentations. In this case series we present history,
      clinical manifestations, KOH smear, and histopathological findings of a series of
      four patients with crusted scabies. Scaly scalp was a prominent feature of the
      disease in all cases. Examination of and treatment of the scalp of patients with
      suspected crusted scabies should not be neglected. A KOH smear from the scalp
      offers a simple and reliable technique for diagnosis.

PMID- 18328213
TI  - Bilateral nevus of Ota in a light-skinned woman.
AB  - Nevus of Ota is a dermal melanocytosis, clinically localized on skin that is
      innervated by the first and second branches of the trigeminal nerve. It occurs
      almost entirely in Asian people. This manifestation is rarely described in light
      skinned non-Asian persons. We present a case of bilateral Ota nevus in a 47-year
      old light-skinned non-Asian woman.

PMID- 18328214
TI  - Acrodermatitis enteropathica-like skin eruption in a case of short bowel syndrome
      following jejuno-transverse colon anastomosis.
AB  - Acrodermatitis enteropathica is a rare autosomal recessive disorder of zinc
      deficiency. Zinc is an essential trace element in human metabolism and acquired
      zinc deficiency may manifest with skin eruptions simulating acrodermatitis
      enteropathica. We report an unusual case of acrodermatitis enteropathica-like
      skin eruption due to deficiency of zinc and other nutritional factors in a
      patient who has undergone extensive small bowel resection and jejuno-transverse
      colon anastomosis for mesenteric ischemia.

PMID- 18328215
TI  - Netherton's syndrome: the importance of eyebrow hair.
AB  - Netherton's syndrome (NS) is a rare autosomal recessive disease associated with
      variable expressions: congenital ichthyosiform erythroderma, ichthyosis linearis
      circumflexa, specific hair shaft defects (trichorrhexis invaginata) and atopic
      diathesis. We report the case of 14-year-old non-identical twins whose diagnosis
      of NS was established on light microscopy of eyebrow hairs. The sisters consulted
      for a severe episode of atopic dermatitis. Skin examination revealed an
      ichthyosiform eruption with generalized, polycyclic erythematous plaques with
      fine double-edged scaling. The flexural creases were lichenified and multiple
      eczematoid patches were noted. Blood investigation revealed eosinophilia and high
      IgE level. Microscopy of scalp hair of the twins was repeatedly normal, but the
      one of the eyebrows revealed typical trichorrhexis invaginata. The presence of
      trichorrhexis invaginata is necessary to make the diagnosis of NS, but its
      identification can be difficult because this defect is variable in time and
      localization. The examination of eyebrow hairs is especially beneficial for
      patients first seen in late childhood and adults.

PMID- 18328216
TI  - Pseudo-Kaposi sarcoma: a challenging vascular phenomenon.
AB  - Pseudo-Kaposi sarcoma is a rare vascular phenomenon which can be related to
      congenital vascular malformations or acquired venous insufficiency. The
      differential diagnosis includes Kaposi sarcoma. In this report, a patient with
      Pseudo-Kaposi sarcoma Stewart-Bluefarb subtype is presented and the related
      literature is reviewed.

PMID- 18328217
TI  - Linear and whorled nevoid hypermelanosis.
AB  - Linear and whorled nevoid hypermelanosis (LWNH) is a rare skin condition
      characterized by swirls and whorls of hyperpigmented macules in a reticulate
      pattern along Blaschko's lines; approximately 40 cases have been reported in the
      English language literature. We report a case of LWNH occurring in a 20-year-old
      man with widespread involvement over the trunk, face, upper limbs, and genitalia
      in association with scoliosis. A small hyperpigmented area on the abdomen was
      treated with a medium-depth chemical peel regimen using 70 percent glycolic acid
      and 35 percent trichloroacetic acid with no benefit. This is the first report of
      LWNH treated with medium-depth chemical peel.

PMID- 18328218
TI  - Nephrogenic fibrosing dermopathy: first Colombian case.
AB  - A 67-year-old woman with acute renal insufficiency, who was on hemodialysis,
      developed progressive skin lesions consistent with thickening and hardening of
      the skin in both the back and extremities without contracture upon flexure. Her
      face was not affected. Laboratory evaluation was unremarkable and a skin biopsy
      showed an increase in collagen and interstitial mucin with no inflammatory
      infiltrate. These clinical features resemble a new recently reported disorder,
      nephrogenic fibrosing dermopathy. This disorder manifests itself as
      scleromyxedema-like skin lesions without associated paraproteinemia, occurring in
      the setting of renal disease. The incidence, prevalence and etiology of the
      disease are unknown and currently no effective treatment is available. This is
      the first case reported in Colombia.

PMID- 18328219
TI  - Bilateral tinea nigra in a temperate climate.
AB  - Tinea nigra is a superficial mycosis associated with a dematiaceous fungus called
      Phaeoannellomyces werneckii. It is clinically characterized by asymptomatic non
      scaly brown and black macules, the most common localization is the palmar region.
      Only one bilateral case occurring on the plantar skin and four palmar bilateral
      cases have been reported. We report the case of a 5-year-old boy presenting two
      hyperpigmented lesions with an irregular contour in both palmar regions, which
      appeared three months prior to presentation. Topical treatment with ketoconazole
      was effective.

PMID- 18328220
TI  - Familial necrobiosis lipoidica not associated with diabetes.
AB  - A 42-year-old woman presented with a 12-year history of extensive yellow and
      erythematous plaques, round and oblong with irregular configuration and glossy
      atrophic central areas on the pretibial aspects of both legs. Her 45-year-old
      sister presented with a 7-year history of a single plaque with erythematous
      margins, abundant telangiectases, and an atrophic center in the lower portion of
      the left leg. There was no family history of type-1 or type-2 diabetes mellitus.
      Both patients had normal fasting glucose concentration, oral glucose tolerance
      test, and glucose overload test. Different treatment options including topical
      corticosteroids were unsuccessful. Treatment with oral fumaric acid esters was
      attempted but the medication was discontinued because of intolerable side effects
      (flushing and gastrointestinal discomfort). At present, after a follow-up of 2
      years, the plaques remain unchanged. These two cases should be added to the few
      cases of familial nondiabetic necrobiosis lipoidica previously reported.

PMID- 18328221
TI  - Acute hemorrhagic edema of infancy: a case report.
AB  - A 12-month-old male presented with edematous purpuric plaques on the extremities
      (including the palms and soles), and violaceous targetoid macules on the hard
      palate and earlobes. The patient had an upper respiratory infection and
      conjunctivitis 10 days prior to the development of the skin lesions, and was
      vaccinated 3 weeks before this presentation. He was found to have increased IgA
      levels and increased ESR. Skin biopsies demonstrated leukocytoclastic vasculitis
      and IgA granular deposition on superficial dermal vessels. These findings are
      characteristic of acute hemorrhagic edema of infancy, an entity that must be
      distinguished from other leukocytoclastic vasculitis, especially Henoch-Schonlein
      purpura.

PMID- 18328222
TI  - A case of bullous Darier's disease histologically mimicking Hailey-Hailey
      disease.
AB  - The bullous variant of Darier's disease is a rare type and the exact nosological
      position relative to Hailey Hailey disease has been doubtful. We report a case of
      bullous Darier's disease with histological picture suggestive of Hailey-Hailey
      disease. We have also reviewed and summarized the differences between Darier's
      disease and Hailey-Hailey disease.

PMID- 18328223
TI  - [Herpes zoster and polyradiculopathy: report of a case].
AB  - Polyradiculopathy that develops as a result of herpes zoster is rare. When it
      does occur, it usually follows the cutaneous eruption. However, we present a case
      of nerve impairment (motor, sensatory, and autonomic) that occurred prior to the
      cutaneous herpes zoster eruption.

PMID- 18328224
TI  - Giant skin tags: report of two cases.
AB  - Skin tags are skin-colored, pedunculated tumors with a smooth surface.
      Histologically are composed by loose collagen fibers and dilated capillaries.
      Giant skin tags are reported rarely in the literature. We present the case of two
      giant skin tags on labium majus. To our knowledge, these are the largest skin
      tags reported.

PMID- 18328225
TI  - Acquired cephalic cutis laxa.

PMID- 18328226
TI  - Time management of patients.

PMID- 18328227
TI  - Should local anesthetics be banned during treatment of palmar hyperhidrosis with
      botulinum toxin A?

PMID- 18328228
TI  - Generalized linear scleroderma in childhood.

PMID- 18328229
TI  - Inclusion and exclusion criteria, methodological flaw and ethical concepts for
      the treatment of patients with ocular Behcet disease.

PMID- 18328230
TI  - Unilateral Blaschkoid lichen planus involving the entire half of the body, a
      unique presentation.
AB  - A large number of congenital as well as acquired skin disorders assume a
      characteristic morphological pattern following the Blaschko lines. Lichen planus
      (LP) is an acquired inflammatory disorder that can come with different faces.
      Linear lesions are frequently seen but cases of zonal (zosteriform) or whorled
      appearance have rarely been described in the literature. We describe an even
      rarer presentation in a 30-years-old man who had unilateral pruritic violaceous
      lesions over right half of body characteristically following lines of Blaschko
      with clinical and histological morphology typical of LP.

PMID- 18328231
TI  - Scar sarcoidosis sparing a surgical scar.

PMID- 18328232
TI  - Mineral trioxide aggregate as a pulpotomy medicament: a narrative review.
AB  - BACKGROUND: Several medicaments have been used to devitalize remaining pulp or
      maintain pulp vitality and promote healing. Based on pulpal biocompatibility and
      good sealing ability, a growing interest in more biocompatible materials promotes
      mineral trioxide aggregate (MTA) as an alternative to traditional medicaments.
      Uniquely, MTA can preserve pulpal health predictably and promote healing with
      pulp regeneration. METHODS: Using electronic search all papers published since
      1993 on the use of MTA in paediatric dentistry were identified. This paper
      provides a narrative review of the current literature on MTA, formocresol, ferric
      sulphate and calcium hydroxide with particular reference to primary teeth
      pulpotomy medication. CONCLUSION: The use of formocresol or formaldehyde-based
      medicaments should be replaced with more biocompatible medicaments possessing
      antimicrobial and pulpal regenerative properties. Of the four pulpotomy
      medicaments discussed, mineral trioxide aggregate is recommended as the
      medicament of choice.

PMID- 18328233
TI  - Prevention of early childhood caries (ECC)--review of literature published 1998
      2007.
AB  - AIM: This was to examine the literature published during the last decade and
      review the effectiveness of methods used for the prevention of early childhood
      caries (ECC). STUDY DESIGN: A critical review of papers. METHODS: A broad search
      of the PubMed database was conducted from 1998 through September 2007, using
      "early childhood caries", "baby bottle tooth decay", "nursing caries", "infant
      caries", "caries prevention" and "oral health education" as index terms. Relevant
      papers published in English between 1998 and 2007 were identified after a review
      of their abstracts. Papers were selected if they reported a prospective
      controlled design with preventive or non-invasive intervention directed to
      children under the age of 3 years. A defined endpoint measure of cavitated or non
      cavitated clinical caries, expressed as incidence or prevalence, was required.
      The targeted publications were critically assessed by the author concerning
      design, methodology and performance. RESULTS: The initial search revealed 66
      papers of which 22 met the inclusion criteria. The results reinforced the role of
      fluoride toothpaste as the most cost-effective home-care measure and semi-annual
      fluoride varnish applications as the best professional method for infants at
      risk. The evidence concerning the preventive effect of antibacterial agents,
      primary-primary prevention and dental health education were inconclusive but the
      included studies supported the importance of early start, outreach activities and
      motivational interviewing as key factors to overcome cultural and socioeconomic
      barriers. CONCLUSIONS: Although there is a body of evidence for the use of
      fluoride in preventing ECC, further high-quality studies are needed to further
      establish the best way to maintain oral health in infants.

PMID- 18328234
TI  - Inheritance of occlusal topography: a twin study.
AB  - AIM: This was to determine the relative contribution of genetic factors on the
      morphology of occlusal surfaces of mandibular primary first molars by employing
      the twin study model. METHODS: The occlusal morphology of mandibular primary
      first molar teeth from dental casts of 9 monozygotic (MZ) twin pairs and 12
      dizygotic (DZ) twin pairs 4 to 7 years old, were digitized by contact-type three
      dimensional (3D) scanner. To compare the similarity of occlusal morphology
      between twin sets, each twin pair of occlusal surfaces was superimposed to
      establish the best fit by using computerized least squared techniques.
      Heritability was computed using a variance component model, adjusted for age and
      gender. RESULTS: DZ pairs demonstrated a greater degree of occlusal morphology
      variance. The total amount of difference in surface overlap was 0.0508 mm (0.0018
      (inches) for the MZ (n=18) sample and 0.095 mm (0.0034 inches) for the DZ (n=24)
      sample and were not statistically significant (p=0.2203). The transformed mean
      differences were not statistically significantly different (p=0.2203).
      Heritability estimates of occlusal surface areas for right and left mandibular
      primary first molars were 97.5% and 98.2% (p<0.0001), respectively. CONCLUSIONS:
      Occlusal morphology of DZ twin pairs was more variable than that of MZ twin
      pairs. Heritability estimates revealed that genetic factors strongly influence
      occlusal morphology of mandibular primary first molars.

PMID- 18328235
TI  - Long-term predictive value of salivary microbial diagnostic tests in children.
AB  - AIM: To investigate in a group of children (n=183) the predictive value of early
      colonization of salivary lactobacilli and candida on caries development in
      primary molars and permanent first molars in 7 years of follow-up time by
      applying a longitudinal survival analysis method. STUDY DESIGN: Longitudinal
      cohort study of clinical outcomes based on dental records. METHODS: The Kaplan
      Meier survival analysis method was used to compare survival times to caries onset
      in primary molars and permanent first molars for children colonized by salivary
      lactobacilli and candida and children who were not colonized by those microbes at
      baseline when children's mean age was 2.5 years. The survival time was the time
      elapsing between the birth of a child and the first restoration as a result of
      dental caries, that is the time when caries has progressed to a stage when a
      dentist has made a decision to restore the affected tooth. RESULTS: The survival
      curves for primary and permanent molars were consistently lower for those
      children whose mouths were colonized by salivary lactobacilli at baseline. A
      statistically significant relationship was found with onset of caries in both
      primary and permanent molars and colonization by salivary lactobacilli. The
      survival of primary second molars was 60% at the age of 9 years in the group
      colonized by lactobacilli and 80% in those children whose mouths were not
      colonized. Colonization by candida was also a significant risk factor for caries
      onset in primary molars but not in permanent first molars. CONCLUSION: Children
      whose mouths were colonized by salivary lactobacilli at baseline were more
      susceptible to caries onset in both primary and permanent molars at any given
      time during follow- up of seven years than children who were not colonized by
      those caries associated microorganisms.

PMID- 18328236
TI  - Effect of thickness of cavity wall on fracture strength of pulpotomized primary
      molar teeth with class II amalgam restorations.
AB  - AIM: This was to evaluate the effect of different thicknesses of cavity walls on
      fracture strength of pulpotomized primary molar teeth with class II amalgam
      restorations. METHODS: 80 carious extracted human primary molar teeth were
      selected for pulpotomy preparation. The teeth were divided into four groups.
      Mesio- or disto-occlusal (20 teeth) and mesio-occluso-distal (20 teeth); cavities
      were prepared in both first and second primary molar teeth. Each group was
      divided into two subgroups of ten teeth according to the thickness of their walls
      (1.5 or 2.5 mm). After restoring teeth with amalgam, all groups were stored in
      distilled water at 37 degrees C for seven days. They were then thermo cycled
      1,000 times between 5 degrees to 55 degrees C. The specimens were then subjected
      to a compressive axial load in a universal testing machine at a crosshead speed
      of 0.5 mm min(-1). The t-test was used for statistical analysis. RESULTS: Mean
      fracture resistances of the first and second molar teeth were 975.5 +/- 368.8 and
      1049.2 +/- 540.1, respectively. In the first molars, fracture resistance of 2
      surface cavities was significantly more than 3-surface cavities (p=0.001), but
      this difference was not statistically significant in second molars. In second
      molars, fracture strength in 2- and 3-surface cavities with a 2.5 mm thickness in
      the walls was more than those with 1.5 mm thickness. However, in first molars
      this difference was only statistically significant in 3-surface cavities
      (p=0.045). CONCLUSIONS: The fracture strength in pulpotomized primary molar teeth
      with amalgam restorations was high, more than maximum bite forces in primary
      teeth, even in extensive 3- surface cavities.

PMID- 18328237
TI  - Of mice and mutations: phenotypic effects of the diabetic db/db and ob/ob
      mutations on the skull and teeth of mice.
AB  - AIM: To compare the phenotypic appearance of the skull bones and teeth of wild
      type C57BL/6J mice with that of diabetic leptin-deficient (ob/ob) and diabetic
      leptin receptordeficient (db/db) mice used as models for diabetes. STUDY DESIGN
      AND METHODS: Skulls were extracted from the carcasses of mice belonging to wild
      type C57B/6J mice, db/db mice on a C57BLKS/J background, and ob/ob mice on a
      C57B/6J background. After removal of overlying tissue, the skulls and mandibles
      were then left to dehydrate and examined for phenotypic variations in structure
      and wear. RESULTS: Bone surfaces of the skulls of wild type mice had a whiter and
      smoother surface compared with a yellowish colour with a grainy texture in the
      two mutant strains. The frontal, parietal and occipital bones were translucent in
      the two mutant strains. Breakages of the zygomatic arches and mandibles were more
      common in the ob/ob and db/db mice than in the wild type mice. Half of the teeth
      of the db/db mice and 90% teeth of the ob/ob mice showed considerable wear
      compared with marginal wear in the wild type mice. CONCLUSIONS: These
      observations suggested that the teeth of the two diabetic mutant strains are
      exhibiting considerable signs of hypomineralization with increased fragility and
      decreased bone thickness.

PMID- 18328238
TI  - Genetics of dental agenesis: anterior and posterior area of the arch.
AB  - AIM: The aim of this study was to evaluate whether or not dental agenesis is
      regulated by genes and, in those cases under genetic control, if there were
      differences between incisors-canines and premolars-molars in the genetic
      transmission of agenesis. METHODS: This study was conducted on all patients who
      presented for a clinical evaluation in the Orthodontic Unit of the Department of
      Dentistry between 2001 and 2002. All patients were screened for dental agenesis.
      At the end of the selection process, 17 patients with dental agenesis, 6 to 20
      years of age, were questioned about their family dental history for the purpose
      of constructing family trees and 15 family trees were constructed. The patients
      were questioned regarding any dental anomalies present. Panoramic radiographs,
      casts, and dental examinations were performed on the patients. For the patient's
      relatives, panoramic radiographs and oral histories were generally collected.
      RESULTS: The most often missing teeth were mandibular second premolars. On the
      basis of the family trees, the data allowed for the identification of two
      different groups: 1) 9 families had dental agenesis as a function of genetic
      transmission and 2) 6 families exhibited dental agenesis as a sporadic condition.
      In the former group of patients, agenesis primarily involved the maxillary
      lateral incisors. This appeared to be transmitted as an autosomal dominant
      characteristic, with variable expression and incomplete penetrance. In these
      families, both in individuals with and without agenesis, other anomalies were
      present, such as supernumerary teeth, microdontia, and anomalous teeth. In these
      cases, agenesis was one of the manifestations of an anomaly of the dental lamina,
      specifically mild dysplasia. In the latter group of patients, agenesis was a
      characteristic present only in orthodontic patients. In this group, agenesis most
      commonly involved the second molars and the second premolars. CONCLUSION: These
      findings indicate that agenesis of anterior teeth may depend on genes, while
      agenesis of posterior teeth is sporadic.

PMID- 18328239
TI  - Paediatric minor oral surgical procedures under inhalation sedation and general
      anaesthetic: a comparison of variety and duration of treatment.
AB  - AIM: To develop baseline data in relation to paediatric minor oral surgical
      procedures undertaken with both general anaesthesia and nitrous oxide inhalation
      sedation within a Hospital Dental Service. STUDY DESIGN: Data were collected
      prospectively over a three-year period from May 2003 to June 2006 for patients
      attending the Departments of Paediatric Dentistry, Dundee Dental Hospital and
      Ninewells Hospital, NHS Tayside, Great Britain, for all surgical procedures
      undertaken with either inhalation sedation or general anaesthetic. Both operator
      status and the procedure being undertaken were noted. In addition, the operating
      time was recorded. RESULTS: Data for 166 patients (F: 102; M: 64) with a median
      age of 12.50 (inter-quartile range 10.00, 14.20) years showed that 195 surgical
      procedures were undertaken. Of these 160 and 35 were with general anaesthetic and
      sedation respectively. The surgical removal of impacted, carious and
      supernumerary unit(s) accounted for 53.8% of all procedures, whilst the exposure
      of impacted teeth and soft tissue surgery represented 34.9% and 11.3% of
      procedures respectively. The median surgical time for techniques undertaken with
      sedation was 30.00 (inter-quartile range 25.00, 43.50) minutes whilst that for
      general anaesthetic was similar at 30.00 (inter-quartile range 15.25, 40.00)
      minutes (not statistically significant, (Mann Whitney U, W = 3081.5, P = 0.331).
      CONCLUSIONS: The majority of paediatric minor oral surgical procedures entail
      surgical exposure or removal of impacted teeth. The median treatment time for
      most procedures undertaken with either general anaesthetic or nitrous oxide
      sedation was 30 minutes.

PMID- 18328240
TI  - Atypical retention of infraoccluded primary molars with permanent successor
      teeth.
AB  - BACKGROUND: Infraocclusion of primary molar teeth is relatively common. The
      majority of infraoccluded primary molars with permanent successors exfoliate
      naturally. There are currently no evidence based guidelines for the treatment of
      infraoccluded primary molars with permanent successor teeth. CASE SERIES: The
      three cases presented demonstrate atypical retention of infraoccluded primary
      molars, following a conservative approach. In case 1 taking a conservative
      approach over 5 years, the infraocclusion became gradually more severe. Tilting
      of the adjacent teeth and the centre-line shift caused by leaving the affected
      tooth in place during dental and alveolar development was significant. In Case 2
      the severely infraoccluded 55 required surgical removal and exposure of the
      underlying permanent successor (15). Case 3 showed a maxillary premolar (14) and
      first permanent molar (16) tilted toward the partially erupted, ectopic, rotated
      15. Surgical removal of the impacted maxillary primary molar was required.
      CONCLUSION: Although there is evidence available to support the conservative
      treatment of such cases, it does not always lead to a favourable outcome.
      Detrimental effects on the adjacent teeth and occlusion were observed and
      surgical intervention was required.

PMID- 18328241
TI  - Presentation of a radicular cyst associated with a primary molar.
AB  - BACKGROUND: A radicular cyst in a 9-year old girl is reported. CASE REPORT: A 9
      year-old child was referred from her General Dental Practitioner because of the
      need for obtaining expert care, assessment and treatment with regards to a
      radiolucency associated with her lower right second primary molar (85).
      TREATMENT: This included surgical intervention for the removal of the affected
      tooth, enucleation of the cyst and primary closure of the surgical area. FOLLOW
      UP: This was satisfactory and 12 months post-operative the patient reported no
      further problems or symptoms. It could be seen that the area previously occupied
      by the cyst had undergone bony infill.

PMID- 18328242
TI  - Child-Centred child management in a changing world.
AB  - BACKGROUND: There is a need to "re-think" child management, as the completion of
      a procedure is not the only dental goal. Short versus long-term goals and the
      behavioural and pharmacologic repertoire will influence outcomes. REVIEW: A child
      centred approach is described, with a specific protocol for the dental waiting
      room. The changing attitudes of society need to be taken into account in the use
      of behaviour management techniques by paediatric dentists. CONCLUSION: The goal
      of managing children in the dental environment requires some thought: the welfare
      of the child depends on attention by a clinician to long term goals. The
      contemporary child-centred clinician has a wide range of child management skills.
      It is not optional for the clinician to develop his/her behavioural expertise to
      a high level; clinician skills have long-term consequences. These days behaviour
      management begins in the waiting room where initial contact provides the
      opportunity to shape subsequent behaviours.

PMID- 18328243
TI  - Dental anxiety and behaviour management problems in paediatric dentistry--a
      review of background factors and diagnostics.
AB  - AIM: To review the literature regarding dental anxiety and dental behaviour
      management in children and adolescents with regards to prevalence, measurement,
      and aetiological factors. STUDY DESIGN: Review. RESULTS: Dental anxiety and
      dental behaviour management problems are two different concepts related to each
      other but not identical. Each affects approximately 9% of the child and
      adolescence populations and both have a multifactorial background. Aetiological
      factors include the dental treatment as such (mainly pain, discomfort, and
      perceived lack of control), general emotional status, and temperament.
      CONCLUSIONS: In order to treat children and adolescents, paediatric dentists need
      to assess the patient in relation to both psychological, personality, and
      treatment aspects, and assessments may be carried out using well established
      methods to gain more knowledge about the individual patient.

PMID- 18328244
TI  - Communicating with children and parents: recommendations for a child-parent
      centred approach for paediatric dentistry.
AB  - BACKGROUND: The European Academy of Paediatric Dentistry has called for a series
      of evidence-based statements to inform their guidelines on the behavioural
      management of the child patient. Communication between dentist, parent and child
      based upon scientifically robust research evidence was felt to be central to this
      request in order to provide empathetic and child-centred care for children and
      their parents attending for dental health care. REVIEW PROCESS: Shekelle and
      colleagues [1999] devised a series of steps to develop an evidence-based clinical
      guideline. This framework allows first, the identification and refinement of the
      subject area and secondly, the identification and assessment of the evidence
      base. Four areas of communication were identified as being of central importance.
      These were identification of the mother-child dyad; affective communication
      skills; problem solving and negotiation skills. CONCLUSION: It was recommended
      that paediatric dentists should become knowledgeable and competent in these
      skills in order to provide patient-centred care for the children and parents
      attending their clinics for dental treatment.

PMID- 18328245
TI  - Child rearing styles, dental anxiety and disruptive behaviour; an exploratory
      study.
AB  - AIM: This was to explore the relation between children's dental anxiety, their
      behaviour during treatment and their parent's rearing style. Also the parents'
      preparation of the child for dental treatment was related to behaviour and
      parental rearing style. METHODS: The parents of 100 children, referred to a
      secondary dental care clinic were asked to fill out the Child Rearing Practices
      Report (CRPR), the Child Fear Survey Schedule (CFSS) on behalf of their children
      and an additional questionnaire on child preparation prior to dental treatment.
      Four rearing styles were constructed by using the results of the Nurturance and
      the Restrictiveness domain of the CRPR. Dentists were asked to assess the
      behaviour of the child during dental habituation and dental treatment using the
      Venham scale. The dentists were unaware of the child's CFSS score. Parents were
      not present during actual dental treatment. RESULTS: Each child's dental anxiety
      was related to their behaviour displayed during dental treatment. Highly anxious
      children showed more disruptive behaviour than their low anxious counterparts
      did, especially during familiarisation. Parental rearing style was neither
      related to child dental anxiety prior to or to behaviour during dental treatment.
      Parents who use a permissive rearing style were less likely to tell their
      children that the dentist will not hurt them compared with authoritarian parents.
      Parents with an authoritative rearing style were more convinced that the
      behaviour of their child could be managed by the dentist than parents with a
      permissive and neglectful rearing style. After their children's dental
      rehabilitation parents were less inclined to accompany their child during
      treatment. CONCLUSIONS: Dental anxiety correlated positively with the behaviour
      displayed during treatment. No relation was found between parenting style and
      dental anxiety and behaviour during treatment. Parents showed more confidence in
      the child-dentist dyad after the rehabilitation of their child's teeth.

PMID- 18328246
TI  - Changes in children's dental fear: a longitudinal study.
AB  - AIM: The study aimed to evaluate the development of dental fear in a low fear
      group and a fearful group of children aged between 8 and 13 years of age and to
      assess the differences between these groups over time taking into account general
      variables, such as gender, and treatment variables, such as restorations.
      Furthermore it was evaluated to what extent general variables and treatment
      variables predict the change in dental fear or dental fear at later age. STUDY
      DESIGN: A three-year longitudinal study. METHODS: 401 parents completed the
      Children's Fear Survey Schedule-Dental Subscale (CFSS-DS), 218 of them repeating
      this after a 3-year interval. Dental records were used to collect the clinical
      data, starting from the children's first dental appointment and the CFSS-DS was
      used to assess the child's dental fear. RESULTS/STATISTICS: Analysis of variance
      for repeated measures showed an interaction effect between fear level and mean
      total CFSS-DS score. Regression analyses applied to the mean total CFSS-DS score
      at the second measurement moment and the change in total CFSS-DS score between
      both measurement moments revealed that little variance could be explained by the
      treatment variables over the various periods, such as extractions in the first
      period, and that child-characteristic variables could not predict much variance.
      Independent-samples t-tests showed a significant difference in means for
      extractions over the whole period between the fearful group (mean=1.73, SD+/
      1.18) and low fear group (mean= 0.68, SD+/-2.01) (t=-4.05, p<0.001, n=218). Also
      the frequency of Behavioural Management Problems (BMP) over the whole period
      differed between these groups (fearful group: mean=1.40, SD+/-1.90 and low
      fearful group: mean= 0.40, SD+/-0.93) (t= -4.58, p<0.001, n=218). CONCLUSION: The
      effect of treatment variables and subjective experiences on child dental fear
      seems to diminish over time. Findings support the theoretical framework of
      conditioning and gradual exposure in children to prevent dental fear.

PMID- 18328247
TI  - Dental anxiety and psychological functioning in children: its relationship with
      behaviour during treatment.
AB  - AIM: In this study the relationship between the levels of dental anxiety,
      psychological functioning and earlier experience with dental injections are
      examined and the possible influence of these factors on children's behaviour
      before and during a local anaesthesia injection. METHODS: A total of 128 children
      (4-11 years) were included. The level of dental anxiety and the psychological
      functioning were measured using the 'Children's Fear Survey Schedule' (CFSS-DS)
      and the 'Strengths and Difficulties Questionnaire' (SDQ). Based on video
      recordings the anxiety behaviour was scored on the Venham-scale. RESULTS: There
      was a positive correlation between levels of dental anxiety, psychological
      functioning and anxiety behaviour before and during the dental injection. In
      particular children with emotional problems or peer problems tended to show more
      anxiety behaviour before the injection and children with emotional or
      hyperactivity problems tend to show more anxiety behaviour during the injection.
      Furthermore, the younger children (below 6 years of age), with previous dental
      experience in the past 6 months, tended to display more anxiety behaviour both
      before and during the injection than children without or with experience from
      longer ago. CONCLUSION: The level of dental anxiety and psychological functioning
      and recent previous dental experience are important factors in determining which
      child is likely to display more anxiety and uncooperative behaviour during
      treatment and therefore potentially need more attention to be able to cope well
      with dental treatment.

PMID- 18328248
TI  - Dental fear in children: clinical consequences. Suggested behaviour management
      strategies in treating children with dental fear.
AB  - AIM: This is to present an overview of behavioural management techniques in the
      dental situation, and to prepare guidelines for the treatment of dentally fearful
      children, focusing on the behavioural management approach. REVIEW: The literature
      related to the behavioural management of children in the dental setting was
      reviewed. Using this material a provisional set of guidelines for behaviour
      management strategies in treating children with dental fear was developed.
      CONCLUSIONS: Effective behavioural strategies that can be used by the dentist are
      discussed, from a theoretical as well as from a clinical point of view. In
      addition, available research studies are discussed and suggestions for guidelines
      in dental practice are presented.

PMID- 18328249
TI  - Binding characterization of the interleukin-13 signaling complex and development
      of a ternary time-resolved fluorescence resonance energy transfer assay.
AB  - Interleukin-13 (IL-13) is a critical mediator of pulmonary pathology associated
      with asthma. Drugs that block the biological function of IL-13 may be an
      effective treatment for asthma. IL-13 signals by forming a ternary complex with
      IL-13Ralpha1 and IL-4R. Genetic variants of IL-13 and of its receptor components
      have been linked to asthma. One in particular, IL-13R110Q, is associated with
      increased IgE levels and asthma. We characterized the interactions of the binary
      complexes composed of IL-13 or IL-13R110Q with IL-13Ralpha1 and the ternary
      complexes composed of IL-13 or IL-13R110Q and IL-13Ralpha1 with IL-4R using
      surface plasmon resonance and time-resolved fluorescence resonance energy
      transfer (TR-FRET). By both biophysical methods, we found no differences between
      IL-13 and IL-13R110Q binding in either the binary or the ternary complex. IL-4R
      bound to the IL-13/IL-13Ralpha1 complex with slow on and off rates, resulting in
      a relatively weak affinity of about 100nM. We developed a TR-FRET assay targeting
      the interaction between the IL-4R and the binary complex. Two antibodies with
      known binding epitopes to IL-13 that block binding to either IL-13Ralpha1 or IL
      4R inhibited the TR-FRET signal formed by the ternary complex. This assay will be
      useful to identify and characterize inhibitory molecules of IL-13 function.

PMID- 18328250
TI  - Assessment of phytoplankton class abundance using in vivo synchronous
      fluorescence spectra.
AB  - In this study the feasibility of using the in vivo synchronous fluorescence
      spectra (SFS) of phytoplankton samples for determining the relative abundance of
      specific classes of phytoplankton was investigated. In total, 405 SFS of nine
      phytoplankton species cultivated under different conditions were measured and
      evaluated. First, principal component analysis (PCA) was used to obtain nine
      representative spectra, and three feature spectrum bands at 200-235, 310-335, and
      355-585 nm of SFS were found to have a better discriminatory capability. The nine
      phytoplankton species were spectrographically sorted into six classes. Second, a
      relationship between the chlorophyll a (chla) concentration of phytoplankton
      extracts and the in vivo SFS intensity was found; thus the corresponding
      phytoplankton class abundance can be expressed by the concentration of standard
      chla. For this data set, the detection limit ranged 1.02-6.89 microg/L chla for
      different classes. Finally, qualitative and quantitative analyses of 30 mixtures
      of phytoplankton were carried out using the nonnegative least square regression
      (NNLS) method. The dominant phytoplankton classes could be identified while the
      qualitative recognition correctness rate was 88% and the quantitative standard
      deviation with fluorometrically determined chla was -0.14-0.04. Hence, it was
      possible to estimate the abundance of dominant phytoplankton classes.

PMID- 18328251
TI  - Solid state fluorescence of lyophilized proteins.
AB  - Fluorescence spectroscopy has been used to measure changes in the tertiary
      structure of proteins in the solution state. The sensitivity of fluorescence to
      the protein tryptophan environment has made it a useful tool for studying protein
      conformation and stability. Using fluorescence spectroscopy to probe structural
      alterations in lyophilized proteins has been limited due to technical challenges
      and overwhelming background light scattering. We have investigated the
      possibility of analyzing lyophilized proteins using the Cary-Eclipse
      spectrofluorometer by monitoring the fluorescence of the protein therapeutic
      after subjecting the lyophilized cake to heat-induced accelerated degradation. We
      have been able to obtain reproducible fluorescence spectra, detecting possible
      structural changes under these conditions. Fluorescence and circular dichroism
      spectroscopic analyses of the reconstituted proteins indicated that changes in
      fluorescence intensities observed in the solid state could be correlated to that
      in solution and to possible tertiary structural changes. Size exclusion
      chromatography analysis of protein Y subject to accelerated degradation showed a
      correlation between decreasing fluorescence intensity and increasing protein Y
      tetramer in solution, consistent with long-term stability. This suggests that
      solid state, intrinsic protein fluorescence measurements using the Cary-Eclipse
      holder may be feasible for long-term stability studies and formulation
      development.

PMID- 18328252
TI  - Universally applicable methods for monitoring response regulator aspartate
      phosphorylation both in vitro and in vivo using Phos-tag-based reagents.
AB  - Recent development of the phosphate chelator, Phos-tag, together with Phos-tag
      pendant reagents, has provided new methods for detection of phosphorylated
      serine, threonine, tyrosine, and histidine residues in phosphoproteins. We have
      investigated the use of Phos-tag for detection and quantification of phospho
      aspartate in response regulator proteins that function within two-component
      signaling systems. Alternative methods are especially important, because the
      labile nature of the acylphosphate bond in response regulator proteins has
      restricted the application of many traditional methods of phosphoprotein
      analysis. We demonstrate that Phos-tag gel stain can be used to detect phospho
      Asp in response regulators and that Phos-tag acrylamide gel electrophoresis can
      be used to separate phosphorylated and unphosphorylated forms of response
      regulator proteins. The latter method, coupled to Western blot analysis, enables
      detection of specific phosphorylated proteins in complex mixtures such as cell
      lysates. Standards of phosphorylated proteins can be used to correct for
      hydrolysis of the labile phospho-Asp bond that invariably occurs during analysis.
      We have employed Phos-tag methods to characterize the phosphorylation state of
      the Escherichia coli response regulator PhoB both in vitro, using purified
      protein, and in vivo, by analyzing lysates of cells grown under different
      conditions of induction of the PhoR/PhoB phosphate assimilation pathway.

PMID- 18328253
TI  - Mutational analysis of ABC proteins.
AB  - The 49 human members of the ATP-binding cassette (ABC) family of proteins are
      involved in a wide range of activities such as active transport of compounds
      across membranes, extraction of compounds out of membranes, functioning as ion
      channels, or regulators of channel activity. Mutations and/or overexpression of
      many of the proteins can have adverse effects on health. A goal in the study of
      ABC proteins is to understand their mechanisms of action. This review will focus
      on the mutational approaches that have been used to study the structure and
      mechanisms of some ABC proteins.

PMID- 18328254
TI  - Characterization of a response regulator protein that binds to Anabaena sp.
      strain L-31 kdp-promoter region.
AB  - The potassium dependent adenosine triphosphatase (Kdp-ATPase), encoded by the kdp
      operon, is a potassium uptake system found in several prokaryotes. The
      cyanobacterium Anabaena sp. strain L-31 shows the presence of two kdp operons
      (kdp1 and kdp2) of which the kdp2 is predominantly induced in response to
      potassium limitation or desiccation stress. Two ORFs, encoding a sensor kinase
      and a response regulator, respectively, were identified upstream of the kdp2
      operon in Anabaena sp. strain L-31. The response regulator protein, tagged with 6
      additional C-terminal histidine residues, was over-expressed in Escherichia coli
      and purified by affinity chromatography. Employing the protein-specific
      antiserum, the response regulator protein was detected in Anabaena L-31 cytosolic
      fractions. The response regulator protein bound to the kdp2 promoter region with
      higher affinity than kdp1 promoter region. Addition of acetyl phosphate increased
      the ability of the protein to bind to kdp2 promoter region by several fold,
      suggesting a phosphorylation-dependent binding of response regulator to the
      promoter. These data implicate the response regulator protein in regulation of
      kdp2 expression in Anabaena sp. strain L-31.

PMID- 18328255
TI  - Regulation of connexons composed of human connexin26 (hCx26) by temperature.
AB  - This report shows that temperature is a latent regulator of the voltage-dependent
      conductance of hemichannels composed of hCx26. The latter were expressed in
      Xenopus oocytes by injection of a mixture of hCx26 cRNA and antisense of
      endogenous Cx38 (anti-Cx38). At 24-25 degrees C, voltage clamp of oocytes at
      potentials above -40 mV evoked outward currents which were not observed in
      control oocytes. These currents were reversibly affected by change in
      temperature. Increasing temperature of the bath solution amplified gradually,
      whereas decreasing bath temperatures below 20 degrees C reduced the current.
      Furthermore analysis revealed that temperature-dependent increase of the
      conductance of the hemichannels did not correlate with a change of the apparent
      gating charge, whereas the half-activation voltage V(1/2) of the hemichannel was
      affected by a temperature change. It is proposed that this finding correlates
      with a temperature-dependent transition into an open state above 20 degrees C. In
      addition, a temperature-dependent release of Lucifer Yellow from loaded liposomes
      containing reconstituted purified and hCx26 hemichannels was observed, which
      indicate that a temperature-dependent regulation of the permeability of hCx26
      hemichannels is not related to intracellular mediators. The involvement of
      temperature to modulate hemichannels as well as of the corresponding gap junction
      channel composed of hCx26 at physiological condition is discussed.

PMID- 18328256
TI  - Involvement of aldolase A in X-ray resistance of human HeLa and UV(r)-1 cells.
AB  - To find novel proteins involved in radio-resistance of human cells, we searched
      for nuclear proteins, whose expression levels alter after X-ray irradiation in
      HeLa cells, using agarose fluorescent two-dimensional differential gel
      electrophoresis following mass spectrometry. We identified 6 proteins, whose
      levels were increased in nuclei 24h after irradiation at 5Gy, including aldolase
      A. Nuclear aldolase A levels increased twofold after the irradiation, however,
      total aldolase A levels did not change. When the expression of aldolase A was
      suppressed by its specific siRNA, sensitization of the suppressed cells to X-ray
      induced cell death was observed. In addition, UV(r)-1 cells with higher aldolase
      A expression exhibited lower sensitivity to X-ray-induced cell death than the
      parental RSa cells with lower aldolase A expression. These results suggest that
      aldolase A may play a role in the radio-response of human cells, probably in
      nuclei, in addition to its glycolytic role in the cytosol.

PMID- 18328257
TI  - Telomerase-mediated life-span extension of human primary fibroblasts by human
      artificial chromosome (HAC) vector.
AB  - Telomerase-mediated life-span extension enables the expansion of normal cells
      without malignant transformation, and thus has been thought to be useful in cell
      therapies. Currently, integrating vectors including the retrovirus are used for
      human telomerase reverse transcriptase (hTERT)-mediated expansion of normal
      cells; however, the use of these vectors potentially causes unexpected
      insertional mutagenesis and/or activation of oncogenes. Here, we established
      normal human fibroblast (hPF) clones retaining non-integrating human artificial
      chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT
      HAC/hPF clones, we observed the telomerase activity and the suppression of
      senescent-associated SA-beta-galactosidase activity. Furthermore, the hTERT
      HAC/hPF clones continued growing beyond 120days after cloning, whereas the hPF
      clones retaining the silent hTERT-HAC senesced within 70days. Thus, hTERT-HAC
      mediated episomal expression of hTERT allows the extension of the life-span of
      human primary cells, implying that gene delivery by non-integrating HAC vectors
      can be used to control cellular proliferative capacity of primary cultured cells.

PMID- 18328258
TI  - MESOMARK kit detects C-ERC/mesothelin, but not SMRP with C-terminus.
AB  - ERC/mesothelin is expressed on the normal mesothelium and some cancers such as
      mesothelioma or ovarian carcinoma. A splicing isoform of ERC/mesothelin (known as
      SMRP), which has an 82-bp insertion and codes for a C-terminus with a
      hydrophilic, presumably soluble, tail instead of a GPI-anchoring signal, has been
      reported as a useful marker for the diagnosis of mesothelioma. However, the
      existence of SMRP has not yet been demonstrated in the serum of mesothelioma
      patients. To elucidate the existence of SMRP, we have established a new enzyme
      linked immunosorbent assay (ELISA) system for SMRP. The ELISA study revealed that
      N- and C-ERC/mesothelin were detected in sera from mesothelioma patients, but not
      SMRP, even in these samples. This result showed that the SMRP detected with
      MESOMARK kit should be lack of soluble C-terminus and indistinguishable from C
      ERC/mesothelin. Further study might be necessary to demonstrate the relationship
      between SMRP and mesothelin.

PMID- 18328259
TI  - Inhibition of alpha-globin gene expression by RNAi.
AB  - RNA interference (RNAi), a process by which target messenger RNA (mRNA) is
      cleaved by small interfering complementary RNA (siRNA), is widely used for
      investigations of regulation of gene expression in various cells. In this study,
      siRNA complementary to 5' region of exon II of alpha-globin mRNA was examined for
      its role in erythroid colony forming cells (ECFCs) isolated from normal
      peripheral blood donor. On day 6 of cell culture, 1x10(6) ECFCs were transfected
      with lipofectamine-containing alpha-globin specific siRNA. After 48h of
      transfection, alpha-globin specific siRNA produced significantly reduction of
      alpha-globin mRNA level in a dose-dependent manner, but it did not affect the
      level of beta-globin mRNA. Significantly, decreased numbers of hemoglobinized
      erythroid cells relative to the control were observed supporting the inhibitory
      effect of this alpha-globin mRNA specific siRNA.

PMID- 18328260
TI  - Interactions of a designed peptide with lipopolysaccharide: Bound conformation
      and anti-endotoxic activity.
AB  - Designed peptides that would selectively interact with lipopolysaccharide (LPS)
      or endotoxin and fold into specific conformations could serve as important
      scaffolds toward the development of antisepsis compounds. Here, we describe
      solution structure of a designed amphipathic peptide, H(2)N-YVKLWRMIKFIR-CONH(2)
      (YW12D) in complex with endotoxin as determined by transferred nuclear Overhauser
      effect spectroscopy. The conformation of the isolated peptide is highly flexible,
      but undergoes a dramatic structural stabilization in the presence of LPS.
      Structure calculations reveal that the peptide presents two amphipathic surfaces
      in its bound state to LPS whereby each surface is characterized by two positive
      charges and a number of aromatic and/or aliphatic residues. ITC data suggests
      that peptide interacts with two molecules of lipid A. In activity assays, YW12D
      exhibits neutralization of LPS toxicity with very little hemolysis of red blood
      cells. Structural and functional properties of YW12D would be applicable in
      designing low molecular weight non-toxic antisepsis molecules.

PMID- 18328261
TI  - Differential effects of prion particle size on infectivity in vivo and in vitro.
AB  - The conversion of cellular prion protein to the disease-associated isoform
      (PrP(Sc)) has been suggested to follow a mechanism of seeded aggregation. Here,
      we show that fragmentation of PrP(Sc) aggregates by sonication increases
      converting activity in cell culture in a way similar to in vitro conversion
      assays. In contrast, under the same conditions the infectious titer of sonicated
      samples in vivo was reduced. We modified the size distribution of PrP(Sc) by
      adsorption to nitrocellulose, which resulted in a reduction of the infectious
      titer in non-sonicated samples and an increase in sonicated samples. Our results
      indicate that NC-adsorption can (i) block some active sites of PrP(Sc) aggregates
      and (ii) reduce the rate of clearance from the brain. For large particles with
      low clearance the effect of NC-particles on the number of available active sites
      may dominate, whereas for smaller particles (i.e. sonicated samples) the effect
      of NC-adsorption on clearance dominates resulting in increased infectivity.

PMID- 18328262
TI  - Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary
      syndromes: relation to coronary artery narrowing and plaques number.
AB  - BACKGROUND: To analyse osteoprotegerin (OPG), and B-type natriuretic peptide
      (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE
      ACS), in relation to clinical presentation and to coronary atherosclerosis
      diffusion. OPG has been found in several tissues, including the cardiovascular
      system, BNP is selectively produced by myocardial cells. METHODS: 178 consecutive
      patients were classified in three groups: stable angina (SA), unstable angina/non
      ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG
      and BNP at hospital admission. We compared both biomarkers in relation to the
      number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to
      the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels were higher in
      patients respect to controls (p<0.0001). Patients with SA showed more elevated
      levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients
      with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l
      p<0.001). A positive relation was found between OPG levels and number of coronary
      plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with
      NSTE-ACS respect to controls and SA patients (p<0.001). Besides, BNP was
      significantly higher in multivessels vs 1-vessel disease (p<0.001). CONCLUSIONS:
      Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the
      number of plaques in the coronary vessels, suggesting its involvement in the
      coronary disease progression. BNP is also increased during NSTE-ACS and more
      associated to coronary narrowing.

PMID- 18328263
TI  - Median differences or actual differences?

PMID- 18328264
TI  - Analysis of the GAD65-GAD65 autoantibody interaction.
AB  - BACKGROUND: GAD(65)Ab are important markers of risk of development of type 1 DM.
      METHODS: With the need to improve the disease specificity of GAD(65)Ab
      measurement in mind, we have analysed the interaction between recombinant human
      GAD(65) and GAD(65)Ab from different groups of subjects in terms of association
      and dissociation rate constants and equilibrium constants. In addition, binding
      of GAD(65)Ab from various groups of subjects to wild-type GAD(65) versus GAD(65)
      containing a mutation E517P was studied. RESULTS: Affinity constants for serum
      GAD(65)Ab in 12 type 1 DM patients ranged from 0.9 x 10(10) L/mol to 11.2 x
      10(10) L/mol and from 0.8 x 10(10) L/mol to 14.0 x 10(10) L/mol in sera from 11
      individuals without type 1 DM. Serum GAD(65)Ab concentrations assessed by
      Scatchard analysis ranged from 0.04 to 24.8 microg/mL in type 1 DM patients
      (n=12) and from 0.04 to 141.8 microg/mL in individuals without type 1 DM (n=11).
      CONCLUSIONS: Overall, our study indicated that GAD(65)Ab in different patients
      studied showed similar association and dissociation rate constants and similar
      affinity constants. However, GAD(65)Ab concentrations vary widely between
      different sera. There was a modest reduction of the median binding of GAD(65)Ab
      to GAD(65) E517P in the group of patients with type 1 DM compared to patients
      without type 1 DM.

PMID- 18328265
TI  - Association of high sensitivity C-reactive protein (hsCRP) and tumour necrosis
      factor-alpha (TNF-alpha) with carotid intimal medial thickness in subjects with
      different grades of glucose intolerance--the Chennai Urban Rural Epidemiology
      Study (CURES-31).
AB  - OBJECTIVE: To assess the association of high sensitivity C-Reactive Protein
      [hsCRP] and Tumour Necrosis Factor-alpha [TNF-alpha] with IMT in Asian Indians
      with different grades of glucose intolerance. DESIGN AND METHODS: Subjects with
      normal glucose tolerance [NGT](n=150), impaired glucose tolerance [IGT] (n=150)
      and type 2 diabetes (DM) (n=150) were recruited from the Chennai Urban Rural
      Epidemiology Study [CURES], in south India. hsCRP was estimated by nephelometry
      and TNF-alpha by enzyme linked immunosorbent assay. Carotid IMT was assessed by
      high resolution B-mode ultrasonography. RESULTS: hsCRP and TNF-alpha levels were
      higher in those with DM [p<0.001] and IGT [p<0.001] compared to NGT. In linear
      regression analysis, both hsCRP [p=0.003] and TNF-alpha [p=0.001] showed an
      association with IMT among NGT subjects even after adjusting for age and gender.
      Among IGT subjects, TNF-alpha was associated with IMT [p<0.001], while no
      association was observed either with hsCRP or TNF-alpha in diabetic subjects. In
      NGT subjects, mean IMT was highest in those with high values [III tertile] of
      both TNF-alpha and hsCRP [0.83+/-0.1 mm; p<0.001] followed by those with high TNF
      alpha+low hsCRP [0.74+/-0.09 mm; p<0.001], high hsCRPlow TNF-alpha [0.67+/-0.09
      mm; p<0.001], and lowest in those with both low TNF-alpha and hsCRP [I tertile]
      [0.63+/-0.05 mm. CONCLUSION: We conclude that in Asian Indians 1. Levels of hsCRP
      and TNF-alpha increase with increasing severity of glucose intolerance 2. Both
      hsCRP and TNF-alpha are associated with IMT in NGT subjects while TNF-alpha alone
      is associated with IMT in IGT subjects 3. hsCRP and TNF-alpha have a cumulative
      effect on mean IMT values in NGT subjects.

PMID- 18328266
TI  - How do in vitro reconstituted actin-based motility assays provide insight into in
      vivo behavior?
AB  - Recent live cell image analysis of actin dynamics in lamellipodia of motile cells
      has shown that regulated treadmilling, which supports actin-based propulsion of
      functionalized particles in biomimetic reconstituted motility assays, is also
      responsible for lamellipodia extension. In both cases, filaments are created by
      branching with Arp2/3 complex only at the membrane or particle surface, grow
      transiently and are capped; ADF/cofilin enhances the treadmilling but does not
      sever filaments in the body of the meshwork. Differences between the cellular and
      biomimetic systems suggest that additional regulatory mechanisms take place in
      lamellipodia.

PMID- 18328267
TI  - Dietary fatty acids and cardiovascular disease: an epidemiological approach.
AB  - The quality of dietary fat in relation to cardiovascular disease forms the basis
      of the diet-heart hypothesis. Current recommendations on dietary fat now
      emphasise quality rather than quantity. The focus of this review is to summarise
      the results from prospective cohort studies on dietary fat and cardiovascular
      disease outcomes. Relatively few prospective cohort studies have found an
      association between dietary fat quality and cardiovascular disease, partly
      because of limitations in estimating dietary intake. Saturated and trans fatty
      acids have increased cardiovascular risk in several studies. Both n-6 and n-3
      polyunsaturated fatty acids have been associated with lower cardiovascular risk.
      Within the n-6 series, linoleic acid seems to decrease cardiovascular risk.
      Within the n-3 series the long-chain fatty acids (eicosapentaenoic and
      docosahexaenoic acids) are associated with decreased risk for especially fatal
      coronary outcomes, whereas the role of alpha-linolenic acid is less clear.
      Dietary fat quality also influences the activity of enzymes involved in the
      desaturation of fatty acids in the body. Serum desaturase indices have been
      consistently associated with adverse cardiovascular outcomes. Data from metabolic
      and clinical studies reinforce findings from observational studies supporting
      recommendations to replace saturated and trans fat with unsaturated fat in the
      prevention of cardiovascular disease.

PMID- 18328269
TI  - Regulation of platelet Rac1 and Cdc42 activation through interaction with
      calmodulin.
AB  - Rac1 and Cdc42 are members of the Rho family of small GTPases and have been shown
      to induce lamellipodia and filopodia formation, respectively. This leads to
      changes in cytoskeleton organization and as a consequence affects cell migration.
      In the present work we demonstrate that endogenous Rac1 and Cdc42 interact with
      calmodulin (CaM) in a Ca(2+)-dependent fashion. The interaction of Rac1 and Cdc42
      with CaM was shown to be direct. This novel interaction was further confirmed in
      platelets using co-immunoprecipitation studies. Using CaM database analysis and
      in vitro peptide competition assays we have identified a 14 amino acid region in
      Rac1 that is essential for CaM binding. The scrambled form of the peptide did not
      bind CaM demonstrating specificity of the predicted CaM binding region in Rac1. A
      similar region capable of binding CaM exists in Cdc42. Furthermore, using the
      optimal activation time-point for each GTPase, the role of CaM in the function of
      Rac1 and Cdc42 was examined. Results demonstrate that in human platelets,
      thrombin caused maximal activation of Rac1 and Cdc42 at ~60 s and ~25 s
      respectively. The potent CaM antagonist W7 abolished thrombin-mediated activation
      of Rac1. However, addition of W7 resulted in the activation of Cdc42 over basal
      and W7 did not inhibit thrombin-mediated activation of Cdc42. The less potent CaM
      inhibitor, W5, did not have any effect on Rac1 and Cdc42 activation. The results
      demonstrate that in platelets, binding of CaM to Rac1 increases its activation
      while its binding to Cdc42 reduces the activation of this GTPase. This suggests
      an important role for CaM in coordinating Rac1 and Cdc42 activation and in the
      regulation of cytoskeleton remodeling.

PMID- 18328268
TI  - Allosteric inhibition of the nonMyristoylated c-Abl tyrosine kinase by
      phosphopeptides derived from Abi1/Hssh3bp1.
AB  - Here we report c-Abl kinase inhibition mediated by a phosphotyrosine located in
      trans in the c-Abl substrate, Abi1. The mechanism, which is pertinent to the
      nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the
      phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif
      to the Abl SH3 domain. Abi1 regulation of c-Abl in vivo appears to play a
      critical role, as demonstrated by inhibition of pY412 phosphorylation of the
      nonmyristoylated Abl by coexpression of Abi1. Pervanadate-induced c-Abl kinase
      activity was also reduced upon expression of the wild type Abi1 but not by
      expression of the Y213 to F213 mutant Abi1 in LNCaP cells, which are naturally
      deficient in the regulatory pY213. Our findings suggest a novel mechanism by
      which Abl kinase is regulated in cells.

PMID- 18328270
TI  - Evidence for a physiological role of intracellularly occurring photolabile
      nitrogen oxides in human skin fibroblasts.
AB  - Nitric oxide (NO) plays a pivotal role in human skin biology. Cutaneous NO can be
      produced enzymatically by NO synthases (NOS) as well as enzyme independently via
      photodecomposition of photolabile nitrogen oxides (PNOs) such as nitrite or
      nitroso compounds, both found in human skin tissue in comparably high
      concentrations. Although the physiological role of NOS-produced NO in human skin
      is well defined, nothing is known about the biological relevance or the chemical
      origin of intracellularly occurring PNOs. We here, for the first time, give
      evidence that in human skin fibroblasts (FB) PNOs represent the oxidation
      products of NOS-produced NO and that in human skin fibroblasts intracellularly
      occurring PNOs effectively protect against the injurious effects of UVA radiation
      by a NO-dependent mechanism. In contrast, in PNO-depleted FB cultures an
      increased susceptibility to UVA-induced lipid peroxidation and cell death is
      observed, whereas supplementation of PNO-depleted FB cultures with physiological
      nitrite concentrations (10 microM) or with exogenously applied NO completely
      restores UVA-increased injuries. Thus, intracellular PNOs are biologically
      relevant and represent an important initial shield functioning in human skin
      physiology against UVA radiation. Consequently, nonphysiological low PNO
      concentrations might promote known UVA-related skin injuries such as premature
      aging and carcinogenesis.

PMID- 18328271
TI  - Effectiveness of 4-hydroxy phenyl N-tert-butylnitrone (4-OHPBN) alone and in
      combination with other antioxidant drugs in the treatment of acute acoustic
      trauma in chinchilla.
AB  - Acute acoustic trauma (AAT) results in oxidative stress to the cochlea through
      overproduction of cellular reactive oxygen, nitrogen, and other free radical
      species appearing from 1 h to 10 days after noise exposure. It has been shown
      that N-acetyl-L-cysteine (NAC), a glutathione prodrug, and acetyl-L-carnitine
      (ALCAR), a mitochondrial biogenesis agent, are effective in reducing noise
      induced hearing loss. Phenyl N-tert-butylnitrone (PBN), a nitrone-based free
      radical trap, appears to suppress oxidative stress in a variety of disorders and
      several biological models. In this study, we tested whether 4-hydroxy PBN (4
      OHPBN), a major metabolite of PBN, administered 4 h after noise exposure is
      effective in treating noise-induced hearing loss and whether a combination of
      antioxidant drugs (4-OHPBN plus NAC and 4-OHPBN plus NAC plus ALCAR) provides
      greater efficacy in attenuating AAT since each agent addresses different injury
      mechanisms. Chinchilla were exposed to a 105 dB octave-band noise centered at 4
      kHz for 6 h. 4-OHPBN and combinations of antioxidant drugs were intraperitoneally
      administered beginning 4 h after noise exposure. Hearing threshold shifts in
      auditory brainstem responses and missing outer hair cell counts were obtained. 4
      OHPBN reduced threshold shifts in a dose-dependent manner while both drug
      combinations showed greater effects. These results demonstrate that 4-OHPBN and
      combinations of antioxidants can effectively treat acute acoustic trauma and drug
      combinations may increase the effectiveness of treatment and decrease the
      required individual medication dose.

PMID- 18328272
TI  - Molecular diversity in the context of leadlikeness: compound properties that
      enable effective biochemical screening.
AB  - Molecular diversity is of vital importance in drug screening in general and for
      the discovery and development of new pharmacophores in particular. Biochemical
      screening is a powerful tool for pharmacophore development given understanding of
      the properties of a good lead compound operating in the biochemical environment.
      The properties of leadlikeness have evolved to accommodate the artificial
      conditions of a biochemical assay. Accordingly, the properties of leadlikeness
      that are suited for screening at protein targets biochemically are different and
      complementary to the properties of druglikeness used to guide the selection of
      good compounds studied biologically in cellular studies and animal models. The
      benefits of leadlikeness in the biochemical screening arena (including fragment
      based screening and co-crystallization studies) are described here and
      recommendations are forwarded for the generation of leadlike molecular diversity.
      Chemically stable low molecular weight 'minimalist' compounds (or fragments) with
      dense heteroatom substitution and variable conformational constraint are promoted
      as conceptually superior compounds for biochemical screening.

PMID- 18328273
TI  - Glutathionylation of the iron superoxide dismutase from the psychrophilic
      eubacterium Pseudoalteromonas haloplanktis.
AB  - Our previous work showed that the adduct between beta-mercaptoethanol and the
      single cysteine residue (Cys57) in superoxide dismutase from the psychrophilic
      eubacterium Pseudoalteromonas haloplanktis (PhSOD) reduces the enzyme
      inactivation by peroxynitrite. In this work, immunoblotting experiments prove
      that peroxynitrite inactivation of PhSOD involves formation of nitrotyrosine
      residue(s). In order to study the role of Cys57 as a redox-sensor residue
      modifiable by cellular thiols, a recombinant PhSOD and two Cys57 mutants were
      produced and characterized. Recombinant and mutant enzymes share similar activity
      and peroxynitrite inactivation, but different reactivity towards three
      glutathione forms. Indeed, oxidized glutathione and S-nitrosoglutathione, but
      reduced glutathione, lead to S-glutathionylation of recombinant PhSOD. This new
      covalent modification for a Fe-SOD does not occur in both Cys57 mutants, thus
      indicating that its target is Cys57. Moreover, mass spectrometry analysis
      confirmed that S-glutathionylation of Cys57 takes place also with endogenous
      PhSOD. Formation of this mixed disulfide in PhSOD protects the enzyme from
      tyrosine nitration and peroxynitrite inactivation. PhSOD undergoes S
      glutathionylation during its overproduction in E. coli cells and in a growing
      culture of P. haloplanktis. In both cases the extent of glutathionylated PhSOD is
      enhanced upon cell exposure to oxidative agents. We suggest that S
      glutathionylation of PhSOD could represent a further cold-adaptation strategy to
      improve the antioxidant cellular defence mechanism.

PMID- 18328275
TI  - Assess, do not assume.

PMID- 18328276
TI  - Improving nursing school diversity through use of a group admission interview.
AB  - Nursing student diversity is a priority of the University of North Florida School
      of Nursing, but faculty members found that the prelicensure track admission
      process favored students with high grade point averages (GPAs) and eliminated
      many potentially good students, including minorities. Adding an interview to the
      admission process resulted in acceptance of highly qualified students while
      giving deserving students, including minority students with good but lower GPAs,
      the opportunity to enter the program. The change in the admission process
      increased minority admissions from a low of 2% to as high as 25%. Neither the
      overall attrition rate nor the licensure examination pass rate has been adversely
      affected.

PMID- 18328277
TI  - Complying with the 2008 National Patient Safety Goals.
AB  - In 2003, the joint commission began publishing National Patient Safety Goals
      (NPSGs) and requiring accredited health care organizations to comply with these
      goals in an effort to reduce the number of medical errors. THE NPSGS are updated
      yearly with new requirements to promote specific improvements in patient safety.
      This article provides a review of the 2008 NPSGs and suggests ways in which
      information technology systems can address health care organizations' compliance
      with some of these goals.

PMID- 18328278
TI  - Improving surgical services performance through changing work culture.
AB  - Children's memorial hospital administrators knew that they needed to improve
      their surgical services infrastructure to accommodate growing patient volume,
      implement new technology, and address a major shift from inpatient to outpatient
      surgery. The hospital partnered with an outside consultant to better understand
      the impact of the work environment and culture on performance and to identify
      opportunities for improvement. During a seven-month period, new work processes,
      tools, and staff training helped significantly boost surgical services volume and
      revenue. Today, the hospital continues to sustain the performance gains achieved
      through the surgical care coordination initiative.

PMID- 18328279
TI  - Nursing resource considerations for implementing an electronic documentation
      system.
AB  - Implementation of an or management information system (ORMIS) requires a
      significant commitment of human resources. The experiences of the personnel at
      The Johns Hopkins Hospital, Baltimore, MD, as they transitioned to using a
      single, unified, computerized ORMIS are detailed in this article. Included are
      discussions of the nursing resources involved in the process, the lessons
      learned, and the work that remains to be completed for the hospital to fully
      utilize the system.

PMID- 18328280
TI  - Surgical patient education related to smoking.
AB  - Estimates indicate that one million patients who smoke present annually in the
      United States for some form of surgical intervention. Smoking is a known cause of
      respiratory complications, hemodynamic fluctuations, and delayed wound healing. A
      literature search revealed a small number of available studies that address the
      education provided to surgical patients who smoke. Information about the effects
      of smoking on surgical outcomes is not routinely provided to smokers. Determining
      the best methods by which to provide smoking cessation counseling will help
      increase patients' chances for a positive surgical outcome.

PMID- 18328281
TI  - Should the entry into nursing practice be the baccalaureate degree?

PMID- 18328282
TI  - SCIP: making complications of surgery the exception rather than the rule.

PMID- 18328284
TI  - Learning more about the science of patient safety.

PMID- 18328287
TI  - Axillary abscess in a patient with Yersinia enterocolitica infection as a result
      of exposure to pork.

PMID- 18328289
TI  - Evaluation of delayed-type hypersensitivity in patients with suspected
      immunodeficiency.

PMID- 18328291
TI  - The Janus faces of allopurinol-allopurinol hypersensitivity syndrome.

PMID- 18328292
TI  - Purpura fulminans secondary to Streptococcus pneumoniae sepsis: unraveling the
      pattern of cytokines.

PMID- 18328294
TI  - Atrial fibrillation ablation: is there any good evidence behind it?

PMID- 18328295
TI  - Teaching "one medicine, one health".

PMID- 18328296
TI  - Antiplatelet therapy for postdischarge medical management of acute coronary
      syndrome.
AB  - Postdischarge management of patients with acute coronary syndrome is often
      suboptimal, despite their high risk of a subsequent event. Updated American
      College of Cardiology/American Heart Association guidelines emphasize the need
      for aggressive modification of risk factors and treatment with antiplatelet,
      antihypertensive, and lipid-lowering agents commenced in-hospital and continued
      long-term. Antiplatelet therapy involving aspirin and clopidogrel is the mainstay
      of secondary risk reduction. Increased adherence to medication and risk factor
      modification at discharge has been demonstrated with acute care quality
      improvement initiatives. Extension of these initiatives to postdischarge care
      will provide data on medication adherence post acute coronary syndrome and
      functional outcomes in the community setting. Successful secondary prevention of
      cardiovascular events requires implementation of evidence-based guidelines by
      physicians, and adherence to pharmacotherapy and lifestyle modifications by
      patients. Primary care physicians are well placed to influence adherence through
      their ongoing relationships with patients and can save lives by implementing
      secondary risk reduction measures after discharge.

PMID- 18328297
TI  - Systolic hypertension in the elderly: addressing an unmet need.
AB  - Systolic hypertension is a major public health issue in the elderly and is often
      under-recognized and under-treated. The concept that systolic blood pressure
      increases with age should be considered a pathophysiologic concept. Aging of the
      cardiovascular system is accompanied by endothelial dysfunction, activation of
      the renin-angiotensin system and, consequently, vascular remodeling. This process
      leads to an increase in large artery stiffness and an increase in arterial wave
      reflections to the heart. These processes in daily clinical practice translate to
      an increase in systolic blood pressure, which is associated with increased
      cardiovascular morbidity and mortality. Evidence-based medicine recommendations
      to treat systolic hypertension in the elderly are based on landmark and recent
      clinical trials, which clearly demonstrated that treatment of isolated systolic
      hypertension is associated with significant decreases in cardiovascular morbidity
      and mortality. However, treatment of systolic hypertension in older adults
      remains disappointing because therapeutic goals often are not reached. Therefore,
      emphasis should be placed on the treatment of systolic hypertension in the
      elderly, and there is need for more effective, individualized antihypertensive
      therapy.

PMID- 18328298
TI  - Chronic rhinosinusitis in adults.
AB  - There is no consensus on diagnostic criteria for chronic rhinosinusitis. By
      convention, the symptoms of chronic rhinosinusitis are similar to those of acute
      rhinosinusitis but last more than 8 weeks. Diagnosis is based on history,
      physical examination, and computed tomography scan of the sinuses or rhinoscopy.
      Treatment options are numerous and, for the most part, not evidence based. They
      include antibiotics, nasal or oral corticosteroids, antihistamines, naval lavage,
      decongestants, immunotherapy, and surgery. Which diagnostic and therapeutic
      options to exercise when, is the focus of this article.

PMID- 18328299
TI  - The pursuer pursued.

PMID- 18328300
TI  - New rash, old foe.

PMID- 18328301
TI  - Misplaced concern.

PMID- 18328302
TI  - A prickly situation.

PMID- 18328303
TI  - Adopting moderate alcohol consumption in middle age: subsequent cardiovascular
      events.
AB  - PURPOSE: Moderate alcohol use is part of a healthy lifestyle, yet current
      guidelines caution nondrinkers against starting to drink alcohol in middle age.
      The purpose of this study was to evaluate whether adopting moderate alcohol
      consumption in middle age would result in subsequent lower cardiovascular risk.
      METHODS: This study examined a cohort of adults aged 45-64 years participating in
      the Atherosclerosis Risk in Communities study over a 10-year period. The primary
      outcome was fatal or nonfatal cardiovascular events. RESULTS: Of 7697
      participants who had no history of cardiovascular disease and were nondrinkers at
      baseline, within a 6-year follow-up period, 6.0% began moderate alcohol
      consumption (2 drinks per day or fewer for men, 1 drink per day or fewer for
      women) and 0.4% began heavier drinking. After 4 years of follow-up, new moderate
      drinkers had a 38% lower chance of developing cardiovascular disease than did
      their persistently nondrinking counterparts. This difference persisted after
      adjustment for demographic and cardiovascular risk factors (odds ratio 0.62, 95%
      confidence interval, 0.40-0.95). There was no difference in all-cause mortality
      between the new drinkers and persistent nondrinkers (odds ratio 0.71, 95%
      confidence interval, 0.31-1.64). CONCLUSION: People who newly begin consuming
      alcohol in middle age rarely do so beyond recommended amounts. Those who begin
      drinking moderately experience a relatively prompt benefit of lower rates of
      cardiovascular disease morbidity with no change in mortality rates after 4 years.

PMID- 18328304
TI  - Potential for interactions between dietary supplements and prescription
      medications.
AB  - PURPOSE: The objective of this study was to assess the frequency of clinically
      significant interactions caused by concurrent use of dietary supplements and
      prescription medication. METHODS: We conducted a cross-sectional, point-of-care
      survey and combined the findings with a review of patient medical records.
      Patients treated at Mayo Clinic (Rochester, Minn) in 6 different specialty
      clinics were surveyed for their use of dietary supplements. Concurrent use of
      prescription medications was obtained from patients' medical records. We used the
      Lexi-Interact online medication and dietary supplement interaction analysis
      program to assess the potential clinical significance of each interaction.
      RESULTS: We surveyed 1818 patients; 1795 responded (overall response rate of
      98.7%) and 710 (39.6%) reported use of dietary supplements. In total, 107
      interactions with potential clinical significance were identified. The 5 most
      common natural products with a potential for interaction (garlic, valerian, kava,
      ginkgo, and St John's wort) accounted for 68% of the potential clinically
      significant interactions. The 4 most common classes of prescription medications
      with a potential for interaction (antithrombotic medications, sedatives,
      antidepressant agents, and antidiabetic agents) accounted for 94% of the
      potential clinically significant interactions. No patient was harmed seriously
      from any interaction. CONCLUSIONS: A small number of prescription medications and
      dietary supplements accounted for most of the interactions. The actual potential
      for harm was low.

PMID- 18328305
TI  - Delays in seeking medical care in hospitalized patients with decompensated heart
      failure.
AB  - PURPOSE: The magnitude of, and factors associated with, prolonged delay in
      seeking medical care in patients with acute myocardial infarction has been well
      described. It is unknown, however, what the extent of, and factors associated
      with, prehospital delay are in patients hospitalized with acute heart failure.
      The purpose of this study was to examine patterns of prehospital delay, and
      factors associated with delay in seeking medical care, in patients hospitalized
      with acute heart failure at all 11 medical centers in the Worcester,
      Massachusetts metropolitan area. METHODS: The medical records of 2587 greater
      Worcester residents with decompensated heart failure who were hospitalized in
      2000 were reviewed for the collection of information about prehospital delay and
      demographic and clinical factors associated with extent of delay. RESULTS:
      Information about acute symptom onset and duration of delay in seeking medical
      care was available in only 44% of the hospital charts of patients with heart
      failure. The average delay time was 13.3 hours, while the median was 2.0 hours.
      Male sex, multiple presenting symptoms, absence of a history of heart failure,
      and seeking medical care between midnight and 6:00 am were associated with
      prolonged prehospital delay. CONCLUSIONS: The results of this study in residents
      of a large New England metropolitan area suggest that patients hospitalized with
      acute heart failure exhibit considerable delays in seeking medical care. Several
      demographic and clinical characteristics were associated with prolonged delay.
      More research is needed to better understand the reasons why patients with this
      serious and increasingly prevalent clinical syndrome delay seeking medical care
      in a timely fashion.

PMID- 18328306
TI  - C-reactive protein is an independent predictor of severity in community-acquired
      pneumonia.
AB  - BACKGROUND: C-reactive protein (CRP) is an acute phase protein synthesized by the
      liver primarily in response to interleukin-6. Initial studies have suggested that
      inflammatory markers may have a role in predicting severity. We investigated
      whether admission and day 4 CRP could predict severity in community-acquired
      pneumonia. METHODS: A prospective study was carried out over a 2-year period in a
      large teaching hospital. CRP was measured on admission and on day 4. The outcomes
      of interest were: 30-day mortality; need for mechanical ventilation and/or
      inotropic support; development of complicated pneumonia (lung abscess, empyema,
      or complicated parapneumonic effusion); the value of predictive tests were
      assessed using multivariate logistic regression. RESULTS: There were 570 patients
      included in the study; 30-day mortality was 9.6%. Low CRP levels showed a high
      negative predictive value for excluding 30-day mortality (CRP <10 mg/L=100%, CRP
      <50=99.1%, CRP <100=98.9%, CRP <200=94.9%). Low admission CRP levels <100 mg/L
      were independently associated with reduced 30-day mortality (odds ratio [OR]
      0.18; 0.04-0.85), P=.03; need for mechanical ventilation and/or inotropic support
      (OR 0.21; 0.14-0.4), P=.002; and complicated pneumonia (OR 0.05; 0.01-0.35),
      P=.003. A CRP that fails to fall by 50% or more within 4 days of admission is
      independently associated with increased 30 day mortality (OR 24.5; 6.4-93.4), P
      <.0001; need for mechanical ventilation and/or inotropic support (OR 7.1; 2.8
      17.8), P <.0001 and complicated pneumonia (OR 15.4; 6.32-37.6), P <.0001.
      CONCLUSIONS: Admission CRP <100 mg/L has reduced risk for 30-day mortality, need
      for mechanical ventilation and/or inotropic support, and complicated pneumonia.
      Failure of CRP to fall by 50% or more at day 4 leads to an increased risk for 30
      day mortality, need for mechanical ventilation and/or inotropic support, and
      complicated pneumonia. C-reactive protein is an independent marker of severity in
      community-acquired pneumonia.

PMID- 18328307
TI  - Venous thromboembolism in patients hospitalized with nephrotic syndrome.
AB  - PURPOSE: Whether pulmonary embolism in patients with the nephrotic syndrome is
      caused by deep venous thrombosis or renal vein thrombosis is controversial. To
      determine which is the likely cause of pulmonary embolism in patients with the
      nephrotic syndrome, we investigated data from the National Hospital Discharge
      Survey. METHODS: The number of patients discharged from nonfederal short-stay
      hospitals in the United States with a diagnostic code of nephrotic syndrome, deep
      venous thrombosis, renal vein thrombosis, and pulmonary embolism was obtained
      using ICD-9-M (International Classification of Diseases, Ninth Revision, Clinical
      Modification) codes. RESULTS: From 1979 to 2005, 925,000 patients were discharged
      from hospitals with the nephrotic syndrome and 898,253,000 patients did not have
      the nephrotic syndrome. With the nephrotic syndrome, 5000 (0.5%) had pulmonary
      embolism, 14,000 (1.5%) had deep venous thrombosis, and fewer than 5000 had renal
      vein thrombosis. The relative risk of pulmonary embolism comparing patients with
      the nephrotic syndrome to those who did not have it was 1.39, and the relative
      risk of deep venous thrombosis was 1.72. Among patients aged 18-39 years, the
      relative risk of deep venous thrombosis was 6.81. From 1991-2005, after venous
      ultrasound was generally available, the relative risk of deep venous thrombosis
      (all ages) was 1.77. CONCLUSION: The nephrotic syndrome is a risk factor for
      venous thromboembolism. This is strikingly apparent in young adults. Renal vein
      thrombosis was uncommon. Therefore, pulmonary embolism, if it occurs, is likely
      to be due to deep venous thrombosis and not renal vein thrombosis.

PMID- 18328308
TI  - Activated partial thromboplastin time and risk of future venous thromboembolism.
AB  - BACKGROUND: Lower activated partial thromboplastin times are associated with
      higher levels of some coagulation factors and may represent a procoagulant
      tendency. METHODS: In the Atherosclerosis Risk in Communities study, we studied
      the 13-year risk of venous thromboembolism in relation to baseline activated
      partial thromboplastin time in 13,880 individuals. We also studied 258 venous
      thromboembolism cases and 589 matched controls with measurements of additional
      coagulation factors. RESULTS: After adjustment for demographics and procoagulant
      factors reflected in the activated partial thromboplastin time (fibrinogen,
      factors VIII, IX, and XI, and von Willebrand factor), participants in the lowest
      2 quartiles of activated partial thromboplastin time compared with the fourth
      quartile had 2.4-fold (95% confidence interval [CI], 1.4-4.2) and 1.9-fold (95%
      CI, 1.1-3.2) higher risks of venous thromboembolism. The risk associated with
      activated partial thromboplastin times below the median was higher for idiopathic
      (odds ratio 5.5; 95% CI, 2.0-15.5) than secondary venous thromboembolism (odds
      ratio 1.74; 95% CI, 0.88-3.43). Subjects with both activated partial
      thromboplastin times below the median and factor V Leiden were 12.6-fold (95% CI,
      5.7-28.0) more likely to develop venous thromboembolism compared with those with
      neither risk factor (P interaction<.01). A lower activated partial thromboplastin
      time also added to the thrombosis risk associated with obesity and elevated D
      dimer. CONCLUSION: A single determination of the activated partial thromboplastin
      time below the median increased the risk of future venous thromboembolism.
      Findings were independent of coagulation factor levels, and a low activated
      partial thromboplastin time added to the risk associated with other risk factors.

PMID- 18328309
TI  - Increased hospital mortality in patients with bedside hippus.
AB  - BACKGROUND: Hippus is a prominent, repetitive oscillation of the pupils. Although
      regarded by some as a normal variant of pupillary unrest, the clinical importance
      of hippus has not been investigated systematically in hospitalized patients.
      METHODS: We conducted a retrospective cohort study of 117 hospitalized patients
      demonstrating hippus. To mitigate observer bias, 486 control patients were
      selected using 2 adjacent admissions by the same attending physician before and
      after each index case. The primary outcomes were mortality during the admission
      and within 30 days of discharge. RESULTS: Patients with bedside hippus were more
      likely to die within 30 days of observation (P <.00005). Independent risk factors
      for death by 30 days were altered mental status (odds ratio [OR] 4.11; 95%
      confidence interval [CI], 2.05-8.25, P <.001), hippus (OR 2.99; 95% CI, 1.46
      6.11, P = .003), cirrhosis (P = .029), and renal disease (P = .054); angiotensin
      system inhibitors were protective (P = .012). Patients with hippus were more
      likely to have altered mental status (OR 11.23; 95% CI, 6.27-20.09, P <.001), a
      history of trauma (OR 3.76; 95% CI, 1.65-8.59, P = .002), cirrhosis (P = .038),
      renal disease (P = .051), and a history of using iron supplements (P = .016).
      CONCLUSION: The recognition of hippus in hospitalized patients is a clinically
      important predictor of early mortality.

PMID- 18328310
TI  - Genetic variation and activity of the renin-angiotensin system and severe
      hypoglycemia in type 1 diabetes.
AB  - BACKGROUND: The deletion-allele of the angiotensin-converting enzyme (ACE) gene
      and elevated ACE activity are associated with increased risk of severe
      hypoglycemia in type 1 diabetes. We explored whether genetic and phenotypic
      variations in other components of the renin-angiotensin system are similarly
      associated. METHODS: Episodes of severe hypoglycemia were recorded in 171
      consecutive type 1 diabetic outpatients during a 1-year follow-up. Participants
      were characterized at baseline by gene polymorphisms in angiotensinogen, ACE,
      angiotensin-II receptor types 1 (AT1R) and 2 (AT2R), and by plasma
      angiotensinogen concentration and serum ACE activity. RESULTS: Three risk factors
      for severe hypoglycemia were identified: plasma angiotensinogen concentration in
      the upper quartile (relative rate [RR] vs. lower quartile 3.1, 95% confidence
      interval [CI,] 1.4-6.8), serum ACE activity in the upper quartile (RR vs. lower
      quartile 2.9, 95% CI, 1.3-6.2), and homo- or hemizygosity for the A-allele of the
      X chromosome-located AT2R 1675G/A polymorphism (RR vs. noncarriers 2.5, 95% CI,
      1.4-5.0). The three risk factors contributed independently to prediction of
      severe hypoglycemia. A backward multiple regression analysis identified a high
      number of renin-angiotensin system-related risk factors and reduced ability to
      perceive hypoglycemic warning symptoms (impaired hypoglycemia awareness) as
      predictors of severe hypoglycemia. CONCLUSIONS: High renin-angiotensin system
      activity and the A-allele of the AT2R 1675G/A polymorphism associate with high
      risk of severe hypoglycemia in type 1 diabetes. A potential preventive effect of
      renin-angiotensin system blocking drugs in patients with recurrent severe
      hypoglycemia merits further investigation.

PMID- 18328311
TI  - A step toward solving the geriatrician shortage.

PMID- 18328312
TI  - Determination of the different oxidation states of As and Sb by a new
      electrochemical hydride generator coupled with atomic fluorescence spectrometry.
AB  - A novel disk electrochemical hydride generator has been developed for the
      determination of As and Sb. Compared with the traditional thin-layer cell, the
      disk cell combined the advantages of quick assembly and easy operation. This
      electrochemical system for hydride generation in neutral buffer solutions has
      been studied for analytical usefulness in coupling with atomic fluorescence
      spectrometry. It was found that the use of neutral phosphate buffer solution
      could markedly increase the fluorescence intensity of As(III) and Sb(III) and
      reduce the impact of cathode erosion on the stability of signal intensity. At the
      same time, the fluorescence intensity of As(V) and Sb(V) were almost suppressed
      totally. The detection limits (3 sigma) of 0.031 microgL(-1) As(III) and 0.026
      microgL(-1) Sb(III) in aqueous solutions were obtained, respectively. The
      precisions (n=11) for 20 microgL(-1) As(III) and Sb(III) were 2.0% and 2.7%,
      respectively. The method was successfully applied for determination of different
      oxidation states of As and Sb in environmental samples.

PMID- 18328313
TI  - Optimisation and critical evaluation of a collision cell technology ICP-MS system
      for the determination of arsenic in foodstuffs of animal origin.
AB  - The determination of arsenic (75As) was studied using an ICP-MS equipped with
      collision cell technology (CCT). Different mixtures of gases (He and H2) were
      tested using HCl conditions and a He flow rate of 4 mL min(-1) was found to be
      suitable for the removal of the poly-atomic spectral interference [40Ar35Cl]+.
      Trueness of the optimised method has been evaluated in both standard and CCT
      modes on six certified reference materials in foodstuffs of animal origin and on
      three external proficiency testing schemes (FAPAS). The results obtained
      generally coincided with the certified values, except for CCT mode in some
      categories of samples (meat, mussels and milk powder), for which a positive bias
      on results was observed due to the formation of poly-atomic interferences within
      the collision cell. The main interferences were studied and their contributions
      estimated. [58Fe16O1H]+ and [74Ge1H]+ were the most significant interferences
      formed in the cell. Finally, different parameters (e.g. hexapole and quadrupole
      bias voltage, nebuliser gas flow) were optimised to try to attenuate these
      interferences.

PMID- 18328314
TI  - Content uniformity determination of pharmaceutical tablets using five near
      infrared reflectance spectrometers: a process analytical technology (PAT)
      approach using robust multivariate calibration transfer algorithms.
AB  - Near-infrared calibration models were developed for the determination of content
      uniformity of pharmaceutical tablets containing 29.4% drug load for two dosage
      strengths (X and Y). Both dosage strengths have a circular geometry and the only
      difference is the size and weight. Strength X samples weigh approximately 425 mg
      with a diameter of 12 mm while strength Y samples, weigh approximately 1700 mg
      with a diameter of 20mm. Data used in this study were acquired from five NIR
      instruments manufactured by two different vendors. One of these spectrometers is
      a dispersive-based NIR system while the other four were Fourier transform (FT)
      based. The transferability of the optimized partial least-squares (PLS)
      calibration models developed on the primary instrument (A) located in a research
      facility was evaluated using spectral data acquired from secondary instruments B,
      C, D and E. Instruments B and E were located in the same research facility as
      spectrometer A while instruments C and D were located in a production facility 35
      miles away. The same set of tablet samples were used to acquire spectral data
      from all instruments. This scenario mimics the conventional pharmaceutical
      technology transfer from research and development to production. Direct cross
      instrument prediction without standardization was performed between the primary
      and each secondary instrument to evaluate the robustness of the primary
      instrument calibration model. For the strength Y samples, this approach was
      successful for data acquired on instruments B, C, and D producing root mean
      square error of prediction (RMSEP) of 1.05, 1.05, and 1.22%, respectively.
      However for instrument E data, this approach was not successful producing an
      RMSEP value of 3.40%. A similar deterioration was observed for the strength X
      samples, with RMSEP values of 2.78, 5.54, 3.40, and 5.78% corresponding to
      spectral data acquired on instruments B, C, D, and E, respectively. To minimize
      the effect of instrument variability, calibration transfer techniques such as
      piecewise direct standardization (PDS) and wavelet hybrid direct standardization
      (WHDS) were used. The PDS approach, the RMSEP values for strength X samples were
      lowered to 1.22, 1.12, 1.19, and 1.08% for instruments B, C, D, and E,
      respectively. Similar improvements were obtained using the WHDS approach with
      RMSEP values of 1.36, 1.42, 1.36, and 0.98% corresponding to instruments B, C, D,
      and E, respectively.

PMID- 18328315
TI  - Palladium nanoparticle decorated carbon ionic liquid electrode for highly
      efficient electrocatalytic oxidation and determination of hydrazine.
AB  - In this work arrays of palladium nanoparticles were synthesized on carbon ionic
      liquid electrode (CILE) (Pd/CILE), and the electrocatalytic oxidation of
      hydrazine was investigated using this electrode. Electrochemical oxidation of
      hydrazine in phosphate buffer (pH 7) was performed using cyclic voltammetry and
      square wave voltammetric techniques (SWV). Using the proposed electrode, a highly
      reproducible and well-defined peak was obtained for hydrazine at a very low
      potential of -0.02V versus Ag/AgCl. A linear dynamic range of 5-800 microM with
      an experimental detection limit of 0.82 microM was obtained. These results show
      that the proposed electrode displays better electrocatalytic activity compared to
      the previously reported palladium modified electrodes towards oxidation of
      hydrazine.

PMID- 18328316
TI  - Electrochemical detection of dopamine using arrays of liquid-liquid micro
      interfaces created within micromachined silicon membranes.
AB  - The detection of protonated dopamine by differential pulse voltammetry (DPV) and
      square wave voltammetry (SWV) at arrays of micro-interfaces between two
      immiscible electrolyte solutions (microITIES) is presented. Microfabricated
      porous silicon membranes (consisting of eight pores, 26.6 microm in radius and
      500 microm pore-pore separation, in a hexagonal layout) were prepared by
      photolithographic and etching procedures. The membrane pores were fabricated with
      hydrophobic internal walls so that the organic phase filled the pores and created
      the liquid interface at the aqueous side of the membrane. These were used for
      harnessing the benefits of three-dimensional diffusion to the interface and for
      interface stabilisation. The liquid-liquid interface provides a simple method to
      overcome the major problem in the voltammetric detection of dopamine at solid
      electrodes due to the co-existence of ascorbate at higher concentrations.
      Selectivity for dopamine over ascorbate was achieved by the use of dibenzo-18
      crown-6 (DB18C6) for the facilitated ion transfer of dopamine across the
      microITIES array. Under these conditions, the presence of ascorbate in excess did
      not interfere in the detection of dopamine and the lowest concentration
      detectable was ca. 0.5 microM. In addition, the drawback of current signal
      saturation (non-linear increase of the peak current with the concentration of
      dopamine) observed at conventional (millimetre-sized) liquid-liquid interfaces
      was overcome using the microfabricated porous membranes.

PMID- 18328317
TI  - Application of head-space solid-phase microextraction coupled to comprehensive
      two-dimensional gas chromatography-time-of-flight mass spectrometry for the
      determination of multiple pesticide residues in tea samples.
AB  - A new method has been developed to detect 36 pesticides that may contaminate tea
      samples (green, black and fruit tea). The hyphenation of solid-phase
      microextraction in head-space mode with a comprehensive two-dimensional gas
      chromatography coupled with high-speed time-of-flight mass spectrometry (HS-SPME
      GCxGC/TOF MS) proved to be a quick alternative to conventional GC/MS methodology
      which employs solvent-based extraction. The key parameters for controlling HS
      SPME performance were optimized, including fiber coating type, temperature and
      absorption time settings and tea matrix modification by adding water.
      Quantification was carried out using matrix-matched calibration. The
      repeatability of measurements, expressed as relative standard deviation (R.S.D.),
      was less than 24% for all analytes. The limits of quantification ranged from 1 to
      28 microgkg(-1). The optimized method was applied to analyze real life samples
      obtained from a retail market. Results generated by the new SPME procedure and
      those obtained by using a conventional one involving ethyl acetate extraction and
      high-performance gel permeation chromatography (HPGPC) clean up agreed with each
      other for positive (containing residue) samples.

PMID- 18328318
TI  - Application of a new hybrid organic-inorganic monolithic column for efficient
      deoxyribonucleic acid purification.
AB  - A new hybrid organic-inorganic monolithic column for efficient deoxyribonucleic
      acid (DNA) extraction was prepared in situ by polymerization of N-(beta
      aminoethyl)-gamma-aminopropyltriethoxysilane (AEAPTES) and tetraethoxysilane
      (TEOS). The main extraction mechanism was based on the Coulombic force between
      DNA and the amino silica hybrid monolithic column. DNA extraction conditions,
      such as pH, ion concentration and type, and loading capacity, were optimized
      online by capillary electrophoresis with laser-induced fluorescence detection.
      Under optimal condition, a 6.0-cm monolithic column provided a capacity of 48 ng
      DNA with an extraction efficiency of 74+/-6.3% (X+/-RSD). The DNA extraction
      process on this monolithic column was carried out in a totally aqueous system for
      the successful purification of DNA and removal of proteins. The PBE2 plasmid
      could be extracted from Bacillus subtilis (B. subtilis) crude lysate within 25
      min, and the purified DNA was suitable for the amplification of a target fragment
      by polymerase chain reaction. This study demonstrates a new attractive solid
      phase support for DNA extraction to meet the increasingly miniaturized and
      automated trends of genetic analyses.

PMID- 18328319
TI  - An environmental friendly method for the automatic determination of hypochlorite
      in commercial products using multisyringe flow injection analysis.
AB  - A multisyringe flow injection analysis system was used for the determination of
      hypochlorite in cleaning agents, by measurement of the native absorbance of
      hypochlorite at 292 nm. The methodology was based on the selective decomposition
      of hypochlorite by a cobalt oxide catalyst giving chloride and oxygen. The
      difference of the absorbance of the sample before and after its pass through a
      cobalt oxide column was selected as analytical signal. As no further reagent was
      required this work can be considered as a contribution to environmental friendly
      analytical chemistry. The entire analytical procedure, including in-line sample
      dilution in three steps was automated by first, dilution in a stirred miniature
      vessel, second by dispersion and third by in-line addition of water using
      multisyringe flow injection technique. The dynamic concentration range was 0.04
      0.78 gL(-1) (relative standard deviation lower than 3%), where the extension of
      the hypochlorite decomposition was of 90+/-4%. The proposed method was
      successfully applied to the analysis of commercial cleaning products. The
      accuracy of the method was established by iodometric titration.

PMID- 18328320
TI  - Rapid structural determination of modified pregnane glycosides from Cynanchum
      forrestii by liquid chromatography-diode-array detection/electrospray ionization
      multi-stage tandem mass spectrometry.
AB  - The fragmentation behaviors of the two types of modified pregnane glycosides from
      Cynanchum forrestii were investigated by positive ion electrospray ionization
      multi-stage tandem mass spectrometry equipped with an ion trap analyzer. The
      spectral data further illuminated the predominance of ESI-MS(n) technique on the
      identification of pregnane glycosides, especially of two sorts of modified
      pregnane glycosides with aglycone skeletons of 13,14:14,15-disecopregnane-type
      and 14,15-secopregnane-type, which differed in the presence of the characteristic
      [M-46+Na]+ ion. For sugar residues, the fragment ions were analyzed and some
      possible fragmentation pathways were proposed, especially for 3-demethyl-2
      deoxythevetose, the glycosidic cleavage reaction was easier to occur than those
      of other sugar units in its moiety. The natures and differences of the pregnane
      cores, and the types and linked sequences of sugar residues were illustrated.
      According to these conclusions, eight new pregnane glycosides in the fraction of
      Cynanchum forrestii were structurally elucidated by HPLC/HRMS and HPLC-DAD/ESI
      MS(n) techniques. Results of the present studies can benefit the rapid
      identification and structural determination of analogous constituents in crude
      plant extracts.

PMID- 18328321
TI  - A fluorescent chemosensor for calcium with excellent storage stability in water.
AB  - This article describes the design, synthesis and characterization of an optical
      sensor suitable for practical measurement of ionized calcium in serum and whole
      blood samples. The key to the development of this sensor is the identification of
      a chemically very stable, nitrogen-containing, calcium selective ionophore,
      coupled with a fluorophore having the correct spectral and electron accepting
      properties. The slope of the sensor is about 34%/mM in the typical clinically
      significant range of 0.32-2.2mM. This sensor has been implemented into the
      disposable cartridge, used for commercially available OPTI CCA analyzer with
      precision better than +/-0.02 mM (1S.D.). The sensor displays excellent stability
      against hydrolysis and oxidation, leading to less than 0.02 mM measurement error
      after 9 months of wet storage at room temperature, up to 30 degrees C.

PMID- 18328322
TI  - Stimuli-responsive hydrogel-silver nanoparticles composite for development of
      localized surface plasmon resonance-based optical biosensor.
AB  - In this paper, the development of a localized surface plasmon resonance (LSPR)
      based optical enzyme biosensor using stimuli-responsive hydrogel-silver
      nanoparticles composite is described. This optical enzyme biosensor was
      constructed by immobilizing glucose oxidase (GOx) into the stimuli-responsive
      hydrogel. When a sample solution such as glucose was applied to the surface of
      this optical enzyme biosensor, the interparticle distances of the silver
      nanoparticles present in the stimuli-responsive hydrogel were increased, and thus
      the absorbance strength of the LSPR was decreased. Furthermore, hydrogen
      peroxide, which was produced by the enzymatic reaction, induced the degradation
      of highly clustered silver nanoparticles by the decomposition of hydrogen
      peroxide. Hence, a drastic LSPR absorbance change, which depends on the glucose
      concentrations, could be observed. On the basis of the abovementioned mechanism,
      the characterization of the LSPR-based optical enzyme biosensor was carried out.
      It was found that the LSPR-based optical enzyme biosensor could be used to
      specifically determine glucose concentrations. Furthermore, the detection limit
      of this biosensor was 10 pM. Therefore, this LSPR-based optical enzyme biosensor
      has the potential to be applied in cost-effective, highly simplified, and highly
      sensitive test kits for medical applications.

PMID- 18328323
TI  - Nonaqueous capillary electrophoresis with laser-induced fluorescence detection: a
      case study of comparison with aqueous media.
AB  - A novel method based on separation by nonaqueous capillary electrophoresis (NACE)
      combined with laser-induced fluorescence (LIF) detection was developed and
      compared with classic aqueous modes of electrophoresis in terms of resolution of
      solutes of interest and sensitivity of the fluorescence detection. Catecholamines
      derivatized with 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) were chosen as
      test analytes for their subtle fluorescence properties. In aqueous systems,
      capillary zone electrophoresis (CZE) was not suitable for the analysis of test
      analytes due to complete fluorescence quenching of NBD-labeled catecholamines in
      neat aqueous buffer. The addition of micelles or microemulsion droplets into
      aqueous running buffer can dramatically improve the fluorescence response, and
      the enhancement seems to be comparable for micellar electrokinetic chromatography
      (MEKC) and microemulsion electrokinetic chromatography (MEEKC). As another
      alternative, NACE separation was advantageous when performing the analysis under
      the optimum separation condition of 20mM sodium tetraborate, 20mM sodium dodecyl
      sulfate (SDS), 0.1% (v/v) glacial acetic acid, 20% (v/v) acetonitrile (ACN) in
      methanol medium after derivatization in ACN/dimethyl sulfoxide (DMSO) (3:2, v/v)
      mixed aprotic solvents containing 20mM ammonium acetate. Compared with
      derivatization and separation in aqueous media, NACE-LIF procedure was proved to
      be superior, providing high sensitivity and short migration time. Under
      respective optimum conditions, the NACE procedure offered the best fluorescence
      response with 5-24 folds enhancement for catecholamines compared to aqueous
      procedures. In addition, the mechanisms of derivatization and separation in
      nonaqueous media were elucidated in detail.

PMID- 18328324
TI  - A solid-phase extraction and size-exclusion liquid chromatographic method for
      polyethylene glycol 25 p-aminobenzoic acid determination in urine: validation for
      urinary excretion studies of users of sunscreens.
AB  - No previous publications about percutaneous absorption of polyethylene glycol 25
      p-aminobenzoic acid (PEG-25 PABA) have been found in the literature and the
      expected levels to be found in human urine after sunscreens use are unknown. The
      method proposed here is suitable to determine PEG-25 PABA in the urine of
      sunscreens users in order to carry out studies on body accumulation/excretion. It
      is based on solid-phase extraction (SPE) with size-exclusion liquid
      chromatography determination. Solid-phase extraction allows the analyte to be
      retained and subsequently eluted for a clean-up, using a silica-based cartridge.
      The size-exclusion liquid chromatography of the eluted allows the rest of matrix
      interferences to be avoided. Fluorescence intensity was measured at
      lambda(em)=350 nm (lambda(exc)=300 nm). The sensitivity of the proposed method is
      in the order of 450+/-5 mLng(-1) and the detection limit (3S(y/x)/b) in the
      measured solutions is in the order of 13 ngmL(-1), that is 2.6 ngmL(-1) in urine
      samples. The method enables PEG-25 PABA to be determined in both, spiked and
      unspiked human urine samples. Results obtained for spiked human urine samples (11
      100 ngmL(-1)) demonstrated the accuracy of the method. The mean relative standard
      deviation of the results was in the order of 3-10%. Three volunteers applied a
      sunscreen lotion containing a 8% PEG-25 PABA sunscreen cream and their urinary
      excretion was controlled from the moment of application until the excreted
      amounts were no longer detectable.

PMID- 18328325
TI  - Optimising cell temperature and dispersion field strength for the screening for
      putrescine and cadaverine with thermal desorption-gas chromatography-differential
      mobility spectrometry.
AB  - Biogenic amines, and putrescine and cadaverine in particular, have significant
      importance in the area of food quality monitoring, and are also potentially
      important markers of infection, for cancer, diabetes, arthritis and cystic
      fibrosis. A thermal desorption-gas chromatograph-heated differential mobility
      spectrometer was constructed and the significant effect of interactions between
      cell temperature and dispersion field strength on the observed responses studied.
      The experiment design was a Box-Wilson central composite design (CCD) over the
      levels of 10-24 kVcm(-1) for dispersion field strength and 100-130 degrees C for
      cell temperature. The optimum values were estimated to be 16.22 kVcm(-1) and 116
      degrees C for putrescine and 14.78 kVcm(-1) and 112 degrees C for cadaverine,
      respectively with an ammonia dopant at 19 mgm(-3). An amine test atmosphere
      generator was constructed and produced stable concentrations of putrescine (7
      mgm(-3)) and cadaverine (4 mgm(-3)) vapours at 50+/-0.5 degrees C. Tenax TA
      Carbotrap adsorbent tubes were used to sample putrescine and cadaverine vapour
      standards and a linear response function over the range of sample masses 5-20 ng
      was obtained at 15.0 kVcm(-1) 115 degrees C, with a R(2) of 0.99 for both
      putrescine and cadaverine. The sample mass at the limit of detection was
      estimated to be 3 ng for putrescine and cadaverine. Preliminary data from
      sampling the headspace of chicken meat revealed a 62% increase in the recovered
      masses of putrescine from 0.84 to 1.36 ng in the sampled air.

PMID- 18328326
TI  - Advanced tip design for liquid phase vibration mode atomic force microscopy.
AB  - We have fabricated polymer tips for atomic force microscopy in order to elucidate
      the effects of tip length and shape on cantilever vibration damping in liquids.
      The vibration damping is investigated by measuring the vibration amplitude of
      cantilevers as a function of tip-sample distance. The cantilever with a short tip
      provides a higher damping effect over long tip-sample distances. When the
      vibration amplitude was rescaled to show the effect of the cantilever width on
      oscillation damping, the vibration amplitude of cantilevers with various tip
      lengths was similarly obtained in a long distance range over 50 microm. This
      similarity is explained by an acoustic damping model in which an acoustic wave is
      generated by the cantilever. Finally, the results indicate a cantilever with a
      sufficiently long tip compared to the cantilever width can dramatically reduce
      the long-range damping effect in a liquid environment.

PMID- 18328327
TI  - Evaluating a Cumaean Sibyl: Domenichino or later? A multi analytical approach.
AB  - The purpose of this study is to clarify important details about a Cumaean Sibyl
      painting that is preserved in a private collection. This work, bearing neither
      signature nor date, has never undergone conservation. It was executed after
      Domenichino's Cumaean Sibyl, a work known to have been used as a model by many
      18th century painters. Investigation of the anonymous artist's painting technique
      and identification of its constituent materials were facilitated by employing
      optical microscopy (OM), scanning electron microscopy (SEM/EDS), FTIR and
      microRaman spectroscopies and high performance liquid chromatography with diode
      array detection (HPLC-DAD). The painter's palette comprised lead white, yellow
      ochre, lead-antimonate yellow (Naples yellow), cinnabar, cochineal lake, madder
      lake, haematite, Prussian blue and carbon black. The detection of Prussian blue
      (synthesized in 1704 and widely used as artist's pigment after 1750) was decisive
      in establishing the work's authenticity for, as such, it cannot be attributed
      either to Domenico Zampieri (1581-1641) or to his apprentices. In addition, the
      identification of Naples yellow, which prevailed in the period from 1750 to 1850,
      supports this statement. Nevertheless, its elaborate painting technique strongly
      suggests an artist greatly influenced by the Renaissance masters. A comparison of
      its stylistic features with those of the Cumaean Sibyl of Angelica Kauffmann
      (1741-1807), a prolific 18th century artist known to have studied and to have
      copied Domenichino's Sibyl, reveals significant similarities between the two in
      composition and palette. The unsigned Sibyl, therefore, could well be by
      Kauffmann.

PMID- 18328328
TI  - Mutations in cytochrome b that affect kinetics of the electron transfer reactions
      at center N in the yeast cytochrome bc1 complex.
AB  - We have examined the pre-steady-state kinetics and thermodynamic properties of
      the b hemes in variants of the yeast cytochrome bc1 complex that have mutations
      in the quinone reductase site (center N). Trp-30 is a highly conserved residue,
      forming a hydrogen bond with the propionate on the high potential b heme (bH
      heme). The substitution by a cysteine (W30C) lowers the redox potential of the
      heme and an apparent consequence is a lower rate of electron transfer between
      quinol and heme at center N. Leu-198 is also in close proximity to the b(H) heme
      and a L198F mutation alters the spectral properties of the heme but has only
      minor effects on its redox properties or the electron transfer kinetics at center
      N. Substitution of Met-221 by glutamine or glutamate results in the loss of a
      hydrophobic interaction that stabilizes the quinone ligands. Ser-20 and Gln-22
      form a hydrogen-bonding network that includes His-202, one of the carbonyl groups
      of the ubiquinone ring, and an active-site water. A S20T mutation has long-range
      structural effects on center P and thermodynamic effects on both b hemes. The
      other mutations (M221E, M221Q, Q22E and Q22T) do not affect the ubiquinol
      oxidation kinetics at center P, but do modify the electron transfer reactions at
      center N to various extents. The pre-steady reduction kinetics suggest that these
      mutations alter the binding of quinone ligands at center N, possibly by widening
      the binding pocket and thus increasing the distance between the substrate and the
      bH heme. These results show that one can distinguish between the contribution of
      structural and thermodynamic factors to center N function.

PMID- 18328329
TI  - Case reports.

PMID- 18328330
TI  - Inadvertent interchange of electrocardiogram limb lead connections. Analysis of
      predicted consequences.

PMID- 18328331
TI  - Is exercise-induced U-wave inversion predictive of proximal left anterior
      descending coronary artery disease?
AB  - A 66-year-old patient with a recent history of chest pain was submitted to
      exercise test. The rest electrocardiogram was normal, but during effort, a
      striking U-wave inversion in the chest leads occurred, not associated with any ST
      segment change. Coronary angiogram demonstrated a severe proximal narrowing of
      the left anterior descending coronary artery. Effort-induced U-wave inversion in
      the precordial leads has long been recognized as a marker of stenosis of the left
      anterior descending coronary artery, but this pattern is seldom taken into
      account.

PMID- 18328332
TI  - Coexistent manifestations of the Andersen-Tawil and Brugada syndromes.

PMID- 18328333
TI  - An unusual electrocardiographic presentation of acute obstruction of the left
      anterior descending coronary artery.
AB  - Acute obstruction of the left anterior descending coronary artery is generally
      presented electrocardiographically as isolated anterior or combined anterior and
      inferior ST-elevation myocardial infarction. We described an isolated
      inferolateral ST-elevation myocardial infarction due to acute occlusion of the
      distal left anterior descending coronary artery.

PMID- 18328334
TI  - Development of more erratic heart rate patterns is associated with mortality post
      myocardial infarction.
AB  - Cardiac patients often have sinus arrhythmia of nonrespiratory origin (erratic
      sinus rhythm [ESR]). ESR was quantified using hourly Poincare and power spectral
      heart rate variability plots from normal-to-normal interbeat intervals and hourly
      values of the short-term fractal scaling exponent and correlations of normal-to
      normal intervals in n = 60 nonsurvivors and n = 66 randomly selected survivors in
      the Cardiac Arrhythmia Suppression Trial. Hours were coded (ABN) as normal (0),
      borderline (0.5), or ESR (1). t Tests compared ABN for n = 2413 paired hours at
      baseline and on therapy. ABN was higher in nonsurvivors (0.38 +/- 0.44 vs 0.28 +/
      0.40, baseline, and 0.51 +/- 0.45 vs 0.34 +/- 0.43, on therapy, P < .001).
      Increased ABN with treatment were greater in nonsurvivors. Normal hours at
      baseline (relative risk = 0.77; 095% confidence interval, 0.62-0.96, P = .018)
      and on treatment (relative risk = 0.47; 95% confidence interval, 0.39-0.58) were
      significantly associated with decreased mortality compared with ESR.
      Quantification of ESR may identify more vulnerable patients or help monitor the
      effects of pharmacologic treatment.

PMID- 18328335
TI  - Magnetocardiography in the evaluation of fetuses at risk for sudden cardiac death
      before birth.
AB  - BACKGROUND: We hypothesized that fetuses at risk for sudden death may have
      abnormal conduction or depolarization, ischemia, or abnormal heart rate
      variability (HRV) detectable by magnetocardiography. METHODS: Using a 37-channel
      biomagnetometer, we evaluated 3 groups of fetuses at risk for sudden death: group
      1, critical aortic stenosis (AS); group 2, arrhythmias; and group 3, heart
      failure and in utero demise. Five to 10 recordings of 10-minute duration were
      recorded, and signal was averaged to determine rhythm, conduction intervals, HRV,
      and T-wave morphology. RESULTS: In group 1, 2 of 3 had atrial and ventricular
      strain patterns. In (n = 53) group 2, 15% had prolonged QTc and 17% had T-wave
      alternans (TWA). Of 23 group 2 fetuses with atrioventricular block, 74% had
      ventricular ectopy, 21% had junctional ectopic tachycardia, and 29% had
      ventricular tachycardia. Group 3 (n = 2) had abnormal HRV and TWA. CONCLUSION:
      Repolarization abnormalities, unexpected arrhythmias, and abnormal HRV suggest an
      arrhythmogenic mechanism for "sudden cardiac death before birth."

PMID- 18328336
TI  - Torsades de pointes related to transient marked QT prolongation following
      successful emergent percutaneous coronary intervention for acute coronary
      syndrome.
AB  - We report 2 patients in whom transient marked QT prolongation occurred after
      successful emergent percutaneous coronary intervention (PCI) for acute coronary
      syndrome. One patient developed torsades de pointes. In both cases, the QT
      interval became markedly prolonged within 24 hours after PCI, and this
      prolongation persisted for 4 days. The T waves had a giant and bizarre negative
      shape with a prolonged T-wave peak to T-wave end interval. No new-onset ischemia
      or congenital long QT syndrome was related to the episodes. The patients had not
      taken any drugs that could have prolonged the QT interval, and their serum
      potassium levels were within normal limits. Torsades de pointes following
      successful PCI for acute coronary syndrome is uncommon, but acquired long QT
      syndrome should be considered and treated in patients in whom giant and bizarre
      negative T waves and QT prolongation develop after PCI.

PMID- 18328337
TI  - Antiarrhythmic effects of growth hormone--in vivo evidence from small-animal
      models of acute myocardial infarction and invasive electrophysiology.
AB  - INTRODUCTION: A growing body of evidence suggests a possible role for growth
      hormone (GH) in the treatment of congestive heart failure (CHF) and myocardial
      infarction (MI). The aim of this study was to investigate in vivo the effects of
      GH treatment on incidence and severity of ventricular arrhythmias normal and MI
      rats. METHODS: Male Sprague-Dawley rats weighing approximately 350 g were
      randomized into 3 groups. Growth hormone-treated rats (n = 6) received 6 mg/kg of
      human GH. The placebo group (n = 10) received 1 mL of saline. Amiodarone-treated
      rats (n = 10) were injected with 25 mg/kg and served as positive controls. All
      animals received a single intraperitoneal injection 6 hours before induction of
      MI. Myocardial infarction was induced by ligation of the left coronary artery,
      resulting in a large (approximately 40%) anterolateral MI. A computerized
      electrocardiographic tracing was obtained continuously before induction of MI and
      up to 1 hour postinfarction. Invasive hemodynamics including intraventricular and
      arterial pressure were registered for 60 minutes post-MI. Qualitative as well as
      quantitative variables of ventricular arrhythmias were analyzed. Invasive
      electrophysiology with pacing in right atrium and ventricle was performed in
      normal rats (control, n = 13; GH, n = 6; amiodarone, n = 6) to asses inducibility
      of supraventricular and ventricular arrhythmias. RESULTS: Growth hormone- and
      amiodarone-treated rats had lower resting heart rate at baseline before induction
      of MI. The arrhythmia scores in the GH- (3.8 +/- 1) and amiodarone-treated (3.9
      +/- 0.5) animals were significant lower than in the placebo group (5.9 +/- 0.5, P
      < .05). There was no significant difference in arrhythmia score between the GH
      and amiodarone groups. The incident of inducible ventricular arrhythmias was
      lower in the GH (2/6, 33%) and amiodarone (2/6, 33%) groups compared with
      controls (13/16, 81%; P = .05). There was no difference in inducibility of atrial
      fibrillation between the GH (5/6, 83%) and control (13/14, 93%) groups, whereas
      the inducibility of atrial fibrillation was significantly lower in the amiodarone
      group (2/6, 33%; P < .05). CONCLUSIONS: Pretreatment with GH reduces the burden
      of ventricular arrhythmias in rats with postinfarction CHF due to acute MI.
      Growth hormone may be useful in the treatment of CHF and acute MI.

PMID- 18328338
TI  - Electrical restitution determined by epicardial contact mapping and surface
      electrocardiogram: its role in ventricular fibrillation inducibility in swine.
AB  - OBJECTIVE: The roles of electrical restitution determined by epicardial contact
      mapping and surface electrocardiogram (ECG) in the inducibility of ventricular
      fibrillation (VF) were evaluated. METHODS: Ten epicardial unipolar electrograms
      using contact mapping and the surface ECGs were simultaneously recorded in 7
      swine. Activation-recovery interval (ARI) and QT-interval restitution curves were
      constructed. Steady-state pacing protocol was performed to induce VF. Ventricular
      fibrillation threshold was defined as the longest pacing interval for inducing
      VF. Statistical correlation analysis was performed to determine the relationship
      between local ARI restitutions, QT-interval restitution, and ventricular
      fibrillation threshold. RESULTS: One hundred thirteen restitution curves were
      constructed (50 in left ventricular sites, 52 in right ventricular sites, and 11
      in surface ECG lead II) from 11 steady-state pacing procedures. Statistical
      correlation between the slopes of the QT restitution curve and the slopes of
      regional ARI restitution curves was noted in several mapping sites. Ventricular
      fibrillation threshold significantly related to the local ARI restitution curve
      slope for the right ventricular apex (R = 0.752, P = .019) and the QT-interval
      restitution curve slope (R = 0.802, P = .005). CONCLUSION: There is a significant
      correlation between the local ARI restitutions and the QT-interval restitutions,
      both of which were associated with VF inducibility.

PMID- 18328339
TI  - Multiple macroreentrant ventricular tachycardias exhibiting centrifugal
      endocardial activations from the scar border zone after myocardial infarction.
AB  - A 53-year-old man with a ventricular tachycardia (VT) electrical storm during the
      chronic phase of an extensive anteroseptal myocardial infarction underwent
      electrophysiologic testing and catheter ablation. An electroanatomical map during
      7 induced macroreentrant VTs demonstrated multiple centrifugal endocardial
      activations from sites that were located at the circumferential border zone of a
      large scar area. Interestingly, during the radiofrequency catheter ablation of 4
      of the VTs, the elimination of the substrate of the previous VTs converted one VT
      to another probably because those VTs might have shared a central common pathway
      of the macroreentrant circuit with different exits.

PMID- 18328340
TI  - Spatial characteristics of atrial fibrillation electrocardiograms.
AB  - BACKGROUND: The present study investigates spatial properties of atrial
      fibrillation (AF) by analyzing vectorcardiogram loops synthesized from 12-lead
      electrocardiograms (ECGs). METHODS: After atrial signal extraction, spatial
      properties are characterized through analysis of successive, fixed-length signal
      segments and expressed in loop orientation, that is, azimuth and elevation, as
      well as in loop morphology, that is, planarity and planar geometry. It is
      hypothesized that more organized AF, expressed by a lower AF frequency, is
      associated with decreased variability in loop morphology. Atrial fibrillation
      frequency is determined using spectral analysis. RESULTS: Twenty-six patients
      with chronic AF were analyzed using 60-second ECG recordings. Loop orientation
      was similar when determined from either entire 60- or 1-second segments. For 1
      second segments, the correlation between AF frequency and the parameters
      planarity and planar geometry were 0.608 (P < .001) and 0.543 (P < .005),
      respectively. CONCLUSIONS: Quantification of AF organization based on AF
      frequency and spatial characteristics from the ECG is possible. The results
      suggested a relatively weak coupling between loop morphology and AF frequency
      when determined from the surface ECG.

PMID- 18328341
TI  - Arrhythmias after Fontan operation: comparison of lateral tunnel and extracardiac
      conduit.
AB  - BACKGROUND: Arrhythmias are frequent causes of morbidity and mortality in
      patients with single ventricle physiology after Fontan operation. The aim of this
      study was to evaluate which type of Fontan procedure--lateral tunnel (LT) or
      extracardiac conduit (EC)--provides superior outcomes related to the problem of
      early postoperative and 1-year follow-up arrhythmias. METHODS: We retrospectively
      analyzed the incidence, types, and duration of rhythm disorders in 101
      consecutive patients who received either LT (n = 60) or EC (n = 41) between April
      1997 and March 2006 in Slovak Children's Cardiac Center, Bratislava (Slovakia).
      Weight, age, sex, and the type of heart morphology did not differ significantly
      between the 2 groups. The rhythm was monitored and documented perioperatively and
      postoperatively with standard electrocardiogram (ECG) recording and continual ECG
      monitoring. Duration of extracorporeal circulation, duration of aortic crossclamp
      and hemodynamic variables were analyzed with respect to the development of early
      arrhythmias in both groups. Twenty-four-hour ECG Holter monitoring (DMS 300-7,
      Holterreader, Producer DMS, Nevada, USA) was used to detect arrhythmias at the 1
      year follow-up. RESULTS: Early postoperative rhythm abnormalities were identified
      in 31 patients (52%) who underwent LT and in 22 patients (54%) who underwent EC.
      The most frequent type of rhythm disturbance was junctional rhythm in both
      groups. The bivariate analysis revealed that there was no significant difference
      in the incidence, type, or duration of early onset arrhythmias between the 2
      groups. Although, there was no significant difference in the duration of
      arrhythmia since the admission form the operating room. The need of aortic
      crossclamp was significantly lower in EC group (P < .001). However, this did not
      correlate with lower incidence of early onset arrhythmias with EC modification.
      At the 1-year follow-up, the prevalence of arrhythmias was similar in both
      groups. CONCLUSIONS: Extracardiac conduit as compared with LT does not provide
      superior outcomes related to the problem of early and 1-year onset arrhythmias.
      Other factors than the risk of early postoperative and early follow-up
      arrhythmias should be considered in surgical preference of modification strategy.

PMID- 18328342
TI  - Use of oral glucose minimal model-derived index of insulin sensitivity in
      subjects with early type 1 diabetes mellitus.
AB  - Insulin resistance plays an important role during various stages of the type 1
      diabetes mellitus disease process. Unfortunately, many of the techniques used to
      measure insulin sensitivity are experimentally laborious and time-consuming and
      are thus impractical for larger clinical and population studies. Therefore, in
      this study, we obtain estimates of insulin sensitivity from a simpler experiment,
      the oral glucose tolerance test (OGTT), and compare them with those from a
      frequently sampled intravenous glucose tolerance test (FSIGT) in a population of
      subjects defined as having early type 1 diabetes mellitus (abnormal 2-hour
      glucose on OGTT) and a group of healthy controls. A total of 19 subjects were
      studied. Eight antibody-positive first- or second-degree relatives of patients
      with type 1 diabetes mellitus and 11 healthy controls underwent both a 3-hour
      OGTT and an insulin-modified FSIGT on separate days. Indices of insulin
      sensitivity (SI) were estimated from the recently derived oral glucose minimal
      model and the original minimal model of glucose kinetics for the OGTT and FSIGT,
      respectively. Estimates of SI from the OGTT correlated closely with those from
      the FSIGT in both early type 1 diabetes mellitus (rs=0.76, P = .04) and healthy
      control (rs = 0.67, P = .03) populations. This preliminary study demonstrates the
      usefulness of OGTT-derived estimates of insulin sensitivity in an early type 1
      diabetes mellitus population. Given the simplicity of the OGTT relative to the
      traditional methods of measuring SI, the oral glucose minimal model may be
      appropriate for large population studies and clinical trials.

PMID- 18328343
TI  - Is albuminuria an indicator of myocardial dysfunction in diabetic patients
      without overt heart disease? A study with Doppler strain and strain rate imaging.
AB  - The aim of this study was to address whether albuminuria could predict myocardial
      dysfunction in diabetic patients without overt heart disease. We studied 67
      patients with normal left ventricular (LV) ejection fraction and no evidence of
      LV hypertrophy or coronary artery disease (47 patients with type 2 diabetes
      mellitus and hypertension and 20 patients with hypertension only). Diabetes
      patients were divided into 3 groups based on albuminuria status: group II = no
      albuminuria (n = 20, <30 mg/d), group III = microalbuminuria (n = 13, 30-300
      mg/d), and group IV = macroalbuminuria (n = 14, >300 mg/d). Twenty patients with
      hypertension only served as a control group (group I). Conventional 2-dimensional
      and Doppler echocardiography was done. Peak strain, peak systolic strain rate
      (SR), and peak diastolic SR of 6 LV segments in the apical views were measured
      and averaged in each patient. Conventional 2-dimensional parameters such as LV
      ejection fraction; left atrium volume index; LV mass; deceleration time; and
      mitral early peak, mitral late peak, myocardial early peak diastolic, and
      myocardial peak systolic velocities were not different among the 4 groups.
      However, peak strains were significantly lower in group III (P = .002) and group
      IV (P < .001) than in group I; and the absolute value of peak systolic SR was
      lower in group III (P = .033) and group IV (P < .001) than in group I.
      Furthermore, the value of peak diastolic SR was lower in group IV than in group I
      (P = .014). In diabetic patients with albuminuria, Doppler strain and SR imaging
      detected subclinical LV systolic and diastolic dysfunction; and albuminuria was
      associated with myocardial dysfunction in diabetic patients without overt heart
      disease.

PMID- 18328344
TI  - Predictors of glycemic control in Japanese subjects with type 2 diabetes
      mellitus.
AB  - The purpose of this study was to investigate which pathophysiological and
      demographic characteristics of Japanese subjects with type 2 diabetes mellitus
      were associated with poor glycemic control and to propose a statistical model for
      predicting their glycemic control. A total of 220 subjects with type 2 diabetes
      mellitus were enrolled in this study. Frequently sampled intravenous glucose
      tolerance test was performed to determine the first-phase C-peptide secretion
      rate (CS1) and insulin sensitivity index. Multiple regression analysis in a
      stepwise manner was carried out to identify independent regulators of glycemic
      control. Upon stepwise linear regression analysis with hemoglobin A1c as a
      dependent parameter, fasting plasma glucose concentration (FPG), CS1, and onset
      age remained as predictors, explaining 41.0% of glycemic control. The young-onset
      group (onset age < or =48 years) had significantly higher hemoglobin A1c than the
      old-onset group (onset age >48 years) (P = .0148), although the present age was
      significantly older in the old-onset group; and there were no significant
      differences in duration of diabetes, treatment, body mass index, FPG, fasting
      insulin level, homeostasis model assessment of insulin resistance, CS1, and
      log(insulin sensitivity index) between them. Worsening factors of glycemic
      control in Japanese subjects with type 2 diabetes mellitus were elevated FPG,
      impaired first-phase insulin secretion, and young age of onset of the disease.
      Because glycemic control in the subjects with young-onset diabetes tends to be
      worse, early and aggressive intervention should be required for those with young
      onset diabetes to prevent long-term complications.

PMID- 18328345
TI  - Maintenance of resting energy expenditure after weight loss in premenopausal
      women: potential benefits of a high-protein, reduced-calorie diet.
AB  - The number of contemporary diet plans promoting high protein intakes for weight
      management has increased dramatically. Complementing this dietary approach with
      increased physical activity has proven to be beneficial. Recent studies have
      suggested that protein intakes in excess of the current Recommended Dietary
      Allowance (0.8 g/kg) may be of metabolic benefit during weight loss. This
      investigation assessed changes in resting energy expenditure and substrate
      oxidation in overweight and obese premenopausal women in response to a weight
      loss intervention that combined a high-protein, reduced-calorie diet with
      increased physical activity. Thirty-nine overweight and obese premenopausal women
      (age, 30.9 +/- 1.5 years; body mass index, 30.2 +/- 0.5 kg/m2) participated in a
      10-week weight loss program in which they ate a reduced-calorie diet for which
      protein provided 30% of total energy and approximated 1.4 g/kg. Subjects
      incrementally increased physical activity (ie, steps walking) throughout the diet
      intervention period. Resting energy expenditure, substrate oxidation, and body
      composition were assessed before (PRE) and after (POST) the 10-week weight loss
      program. Subjects experienced a 5% decrease in body weight, with significant
      decreases in both fat mass (PRE, 35.5 +/- 1.2 kg; POST, 32.4 +/- 1.1 kg; P <
      .0001) and fat-free mass (PRE, 44.6 +/- 0.7 kg; POST, 43.6 +/- 0.7 kg; P <
      .0001). Changes in body weight or body composition did not alter resting energy
      expenditure. Protein oxidation increased (PRE, 18% +/- 1%; POST, 20% +/- 1%; P <
      .05) and fat oxidation decreased (PRE, 37% +/- 3%; POST, 30% +/- 3%; P < .05)
      after the 10-week intervention. These findings illustrate that a weight loss
      intervention combining consumption of a high-protein, reduced-calorie diet with
      increased physical activity promotes weight loss without negatively impacting
      resting energy expenditure in this population of women.

PMID- 18328346
TI  - The antiadipogenic effect of macrophage-conditioned medium depends on ERK1/2
      activation.
AB  - The proatherogenic state of obesity is associated with hypertrophied adipocytes
      that may arise because of deficient adipogenesis. Macrophages infiltrate adipose
      tissue as a function of obesity and may release factors that attenuate
      adipogenesis. Macrophage-conditioned medium inhibits human and 3T3-L1 adipocyte
      differentiation in culture, but underlying molecular mechanisms have yet to be
      defined. Exposure of 3T3-L1 cells throughout the 8-day period of differentiation
      to medium conditioned by THP-1 macrophages (THP-1-MacCM) blocked adipogenesis.
      Triacylglycerol (TG) accumulation and induction of peroxisome proliferator
      activated receptor gamma and fatty acid synthase protein levels were inhibited by
      59% (n = 4, P < .001), 29% (n = 4, P < .01), and 47% (n = 4, P < .01),
      respectively. THP-1-MacCM had no effect when added after the first 2 days of
      differentiation, indicating that early exposure of its targets must be needed to
      inhibit 3T3-L1 adipogenesis. Cell enumeration revealed a 44% decrease in clonal
      expansion compared with standard differentiation (n = 3, P < .01). Addition of
      THP-1-MacCM to 3T3-L1 preadipocytes increased ERK1/2 phosphorylation by 6.5-fold
      (n = 3, P < .01). PD98059 (an inhibitor of the ERK1/2 pathway) impaired the
      negative effect of THP-1-MacCM on TG accumulation, indicated by an inhibition of
      25% vs 69% (n = 3, P < .001), without altering fatty acid synthase or peroxisome
      proliferator-activated receptor gamma levels. Our data implicate ERK1/2 as an
      important signaling mediator for the inhibitory effect of THP-1-MacCM on TG
      accumulation during 3T3-L1 adipogenesis.

PMID- 18328347
TI  - Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change
      in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet
      in obese women.
AB  - Although circulating glycosylphosphatidylinositol-specific phospholipase D (GPI
      PLD), a minor high-density lipoprotein-associated protein, is elevated in
      patients with insulin resistance or high triglycerides, no information is
      available on the effect of weight loss or changes in insulin sensitivity on
      circulating GPI-PLD levels. The objective of the study was to determine the
      effect of weight loss and changes in insulin sensitivity on plasma GPI-PLD
      levels. Forty-two nondiabetic obese women were included in the study, which
      involved a 3-month dietary intervention randomizing patients to a low-fat or a
      low-carbohydrate diet. The study's main outcome measures were plasma GPI-PLD
      levels and insulin sensitivity as estimated by the homeostasis model assessment.
      The very low carbohydrate diet group lost more weight after 3 months (-7.6 +/-
      3.2 vs -4.2 +/- 3.5 kg, P < .01), although the decrease in insulin resistance was
      similar between groups. Weight loss with either diet did not alter plasma GPI-PLD
      levels. However, baseline GPI-PLD levels correlated with the change in insulin
      sensitivity in response to the low-fat diet, whereas baseline insulin sensitivity
      correlated with the change in insulin sensitivity in response to the low
      carbohydrate diet. Plasma GPI-PLD may serve as a clinical tool to determine the
      effect of a low-fat diet on insulin sensitivity.

PMID- 18328348
TI  - Effects of rosiglitazone on body fat distribution and insulin sensitivity in
      Korean type 2 diabetes mellitus patients.
AB  - The objective of the study was to investigate the effects of rosiglitazone (RSG),
      a thiazolidinedione derivative, on body fat distribution and insulin sensitivity
      in Korean subjects with type 2 diabetes mellitus. This study was a phase IV,
      multicenter, single-blind, positive-controlled parallel group study. Eighty-nine
      patients with type 2 diabetes mellitus, aged 30 to 75 years, were enrolled in
      this study. Their fasting plasma glucose levels ranged from 126 to 270 mg/dL, and
      subjects had hemoglobin A1c levels of greater than 7.0%. We compared the effect
      of the treatment with glibenclamide plus RSG 4 mg/d (increased to 8 mg/d after 6
      months) with glibenclamide plus placebo on body fat distributions, which were
      determined by computed tomography scanning and glycemic and insulinemic responses
      to oral glucose load. During the 12-month treatment period, the difference
      between the changes in the ratio of the intraabdominal adipose tissue (IAAT) to
      abdominal subcutaneous adipose tissue areas (SAT) between treatment groups was
      significant (from 1.13 +/- 0.53 to 1.00 +/- 0.40 in the RSG group and from 0.92
      +/- 0.54 to 0.96 +/- 0.62 in the placebo group, P = .0351). The glycemic
      responses to oral glucose load (area under the curve, millimoles per liter per
      hour) were improved in the RSG group with 12 months of treatment (from 4.88 +/-
      1.10 to 4.38 +/- 1.35 in 1 hour and from 13.78 +/- 2.83 to 12.16 +/- 2.52 in 2
      hours), and the difference between the changes of the glycemic response showed
      statistical significance between groups (RSG group vs placebo group: -0.53 +/-
      1.42 vs 0.38 +/- 1.31, difference in 1 hour; -0.76 +/- 2.98 vs 1.43 +/- 2.58,
      difference in 2 hours). However, there was no difference between insulin
      responses from baseline to follow-up and no differences in the change in insulin
      response between groups. In Korean subjects with type 2 diabetes mellitus, 12
      months of treatment with RSG may increase SAT, but may have a neutral effect on
      IAAT, resulting in a decrease in the IAAT:SAT ratio. The RSG treatment improved
      the glucose control in type 2 diabetes mellitus. However, it is important to
      determine whether the glucose-lowering effect of RSG occurs mainly through direct
      enhancement of insulin sensitivity.

PMID- 18328349
TI  - Resistin increases with obesity and atherosclerotic risk factors in patients with
      myocardial infarction.
AB  - The objective of the study was to assess the relation of resistin to the
      anthropometric parameters, metabolic risk factors, and C-reactive protein (CRP)
      in men with myocardial infarction. Subjects were 40 obese (age, 53.6 +/- 7.39
      years; body mass index, > or =30 kg/m2) and 40 lean (age, 54.4 +/- 6.62 years;
      body mass index, <25 kg/m2) men with first acute myocardial infarction. Waist and
      hip circumferences, CRP, uric acid, fasting glucose, lipid profile, and blood
      resistin concentration were measured. In obese patients, triglycerides, fasting
      glucose, and CRP were significantly higher whereas high-density lipoprotein
      cholesterol was lower than in lean patients. The range of blood resistin
      concentration was 6.0 to 70.5 ng/mL: 27.84 +/- 12.15 ng/mL in obese subjects and
      17.35 +/- 11.08 ng/mL in lean subjects (P < .0001). Significant positive
      correlation was revealed between blood resistin concentration and each of the
      analyzed anthropometric parameter and with fasting glucose, low-density
      lipoprotein cholesterol, and CRP, whereas negative relation was observed between
      resistin and high-density lipoprotein cholesterol. As revealed by univariate
      logistic regression analysis, risk of blood resistin concentration being greater
      than the median value (19.75 ng/mL) was increased by obesity, high-density
      lipoprotein cholesterol <40 mg/dL, hypertension, and CRP. In multivariate model,
      independent variables associated with higher median of resistin were obesity and
      CRP. Obesity increased 5.5-fold the probability of blood resistin concentration
      being greater than 19.75 ng/mL, whereas each 1-mg/dL increase in CRP increased
      this probability by 13%. In patients with acute myocardial infarction, obesity is
      positively related to blood resistin concentration. Resistin is likely to play a
      major role in the atherogenesis and its complications, and this action seems to
      be mostly related to the inflammatory reaction.

PMID- 18328350
TI  - Relationship between plasma resistin concentrations, inflammatory chemokines, and
      components of the metabolic syndrome in adults.
AB  - Recent data suggest that resistin, an adipocyte-derived cytokine, has a putative
      role in inflammatory processes and metabolic derangements. In vitro data suggest
      that resistin stimulates the production of inflammatory chemokines, yet the
      relationship in vivo is largely unknown. The purpose of this study was to
      determine if a relationship exists between plasma resistin concentrations, plasma
      inflammatory chemokine aged concentrations (ie, monocyte chemoattractant protein
      1 [MCP-1] and epithelial neutrophil activator 78 [ENA-78]), and components of the
      metabolic syndrome in nondiabetic subjects without known cardiovascular disease
      (CVD). Plasma samples were obtained from nondiabetic subjects (N = 123) aged 18
      to 55 years without known CVD or CVD risk equivalents. The presence of the
      metabolic syndrome was assessed using consensus guidelines. Fasting plasma
      resistin, MCP-1, ENA-78, and high-sensitivity C-reactive protein (hs-CRP)
      concentrations were analyzed. The study population consisted of 67.5% women and
      68.3% Caucasians (mean age = 44 +/- 7 years and mean body mass index = 33.3 +/- 6
      kg/m(2)). The metabolic syndrome was present in 46.3% of study participants.
      Resistin concentrations were significantly correlated with white blood cell count
      (r = 0.326, P < .001), hs-CRP concentrations (r = 0.293, P = .005), MCP-1
      concentrations (r = 0.251, P = .005), body mass index (r = 0.193, P = .033), and
      high-density lipoprotein cholesterol (r = -0.182, P = .044). Resistin
      concentrations were 1.21 times higher in subjects with the metabolic syndrome
      compared with those without the metabolic syndrome (P = .003). In stepwise
      regression analysis, white blood cell count (P < .001) and MCP-1 concentrations
      (P = .002) were significantly associated with resistin concentrations,
      independent of hs-CRP, sex, body mass index, presence of the metabolic syndrome,
      and high-density lipoprotein cholesterol. Data from our cross-sectional study
      demonstrate that plasma resistin concentrations are associated with circulating
      chemokine markers of inflammation, namely, MCP-1, and white blood cell count in
      nondiabetic adults without CVD. Future studies examining the causal relationship
      between plasma resistin concentrations, chemokine markers of inflammation, CVD,
      and diabetes are warranted.

PMID- 18328351
TI  - Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA) gene
      V115F (G-->T) polymorphism is associated with phenotypes of metabolic syndrome in
      Japanese men.
AB  - Cell death-inducing DNA fragmentation factor alpha-like effector A (CIDEA)
      regulates energy expenditure in the adipose tissue and is implicated in the
      development of obesity. A single nucleotide polymorphism in the CIDEA gene that
      causes an amino acid substitution of valine 115 to c(V115F) has recently been
      shown to be associated with obesity in the Swedish population. Here, we
      determined the effects of this polymorphism on phenotypes of metabolic syndrome
      within the Japanese population. Two hundred seventy unrelated Japanese male
      workers (mean age, 44.5 years) were analyzed in a cross-sectional study. The
      clinical features regarding metabolic syndrome, as well as CIDEA V115F
      polymorphism, were determined for each individual. The V115F polymorphism
      associated with waist circumference and fasting plasma glucose. These parameters
      were at higher levels in the VF + FF group than in the VV group (P < .05). The VF
      + FF group compared with the VV group had a higher prevalence for abdominal
      obesity (odds ratio [OR] = 1.89; 95% confidence interval [CI], 1.03-3.44), high
      fasting plasma glucose (OR = 2.81; 95% CI, 1.03-7.67), and metabolic syndrome (OR
      = 3.15; 95% CI, 1.05-9.48). These results suggest that the F allele of the CIDEA
      gene may serve as a risk factor for phenotypes related to metabolic syndrome in
      Japanese men.

PMID- 18328352
TI  - Is there any association between subcutaneous adipose tissue area and plasma
      total and high molecular weight adiponectin levels?
AB  - This study was conducted for the purpose of clarifying the correlations between
      the subcutaneous adipose tissue area and plasma total and high-molecular weight
      (HMW) adiponectin levels. The subjects of this study comprised 359 men and 142
      women who underwent general health examinations from October 2005 to December
      2006. The abdominal subcutaneous and visceral adipose tissue areas were measured
      using low-dose x-ray computed tomography. Total and HMW adiponectin levels were
      measured using the enzyme-linked immunosorbent assay system based on a monoclonal
      antibody to humans. There were negative correlations between the plasma total and
      HMW adiponectin levels and visceral and subcutaneous adipose tissue areas using
      simple correlation analysis. Multiple linear regression analysis clearly
      indicated that the subcutaneous adipose tissue area was independently correlated
      with the HMW adiponectin levels in men and closely related in women. Many studies
      reported that only the visceral adipose tissue area showed a significant
      correlation with metabolic syndrome. However, these results clearly indicate that
      it is also important to consider the subcutaneous adipose tissue area in
      metabolic syndrome.

PMID- 18328353
TI  - Body mass index status is effective in identifying metabolic syndrome components
      and insulin resistance in Pacific Island teenagers living in New Zealand.
AB  - Although adults of Pacific ethnicity living in New Zealand have more than double
      the prevalence of diabetes and cardiovascular disease than the general
      population, little is known regarding the presence of risk factors for these
      disorders among young Pacific Islanders. The study aim was to examine
      relationships between body composition, glucose and lipid metabolism, and
      components of the metabolic syndrome (MS) in a community sample of Pacific Island
      (PI) teenagers living in Dunedin. Anthropometry, body composition (dual-energy x
      ray absorptiometry), glucose and lipid metabolism, insulin resistance
      (homeostasis model assessment [HOMA2], McAuley index), and components of MS were
      assessed in 80 PI teenagers (aged 15-18 years). Results showed that 6
      participants had full MS, 2 had high fasting blood glucose values (>7.0 mmol/L),
      55 had high adiposity, and 21 had insulin resistance. Assessment of the
      components of MS by body mass index (BMI) status showed that obese participants
      (n = 29) had a high prevalence (86.2% had one or more component), whereas only
      10.5% of those with healthy BMI status (n = 19) had any MS component. Elevated
      fat mass had substantial effects on fasting insulin values, HOMA2, and the
      McAuley index because in data adjusted for age, sex, and lean mass, a 10% greater
      fat mass was associated with a 4.7% increase in fasting insulin, a 5.3% rise in
      HOMA2, and a 2.3% decrease in the McAuley index. Our results suggest that the
      antecedents of cardiovascular disease and type 2 diabetes mellitus occur
      frequently in young Pacific Islanders having high adiposity. We conclude that
      community studies of PI adolescents should focus on assessing risk factors
      whenever BMI values are high.

PMID- 18328354
TI  - Cinacalcet for the treatment of primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (HPT) is the leading cause of hypercalcemia in the
      outpatient setting, and it is treated primarily by parathyroidectomy. There are
      few nonsurgical treatment options for patients who do not wish to have surgery,
      who have failed surgery, or who have contraindications to surgery. Cinacalcet
      increases the sensitivity of parathyroid calcium-sensing receptors to
      extracellular calcium, thereby reducing serum calcium levels. We conducted a
      retrospective chart review from 2004 to 2006 to investigate the efficacy of
      cinacalcet in reducing serum total calcium, ionized calcium, and parathyroid
      hormone (PTH) in patients with primary HPT. Patients were started on cinacalcet
      if they met at least one indication for parathyroidectomy, which includes T score
      less than -2.5 standard deviations from the mean, serum calcium 1 mg/dL above the
      upper limit of normal, 24-hour urine calcium above 400 mg/dL, age less than 50
      years, or a creatinine clearance that is 30% below age- and sex-matched controls.
      The primary outcome was normalization of serum calcium. A total of 18 patients
      with primary HPT were started on cinacalcet: 16 men and 2 women with a mean age
      of 70 years. Mean baseline serum calcium was 10.60 +/- .53 mg/dL; ionized serum
      calcium, 1.45 +/- .07 mmol/L; and serum PTH, 141 +/- 78 pg/mL. After treatment
      with cinacalcet, the mean serum calcium decreased to 9.46 +/- .34 mg/dL, ionized
      calcium decreased to 1.26 +/- .06 mmol/L, and PTH decreased to 108 +/- 64.5
      pg/mL. Ninety-four percent of the patients on cinacalcet had normal total serum
      calcium, 81% had normal serum ionized calcium, whereas only 25% had a normal
      serum PTH level. Cinacalcet normalizes serum calcium in most patients while only
      modestly reducing serum PTH levels.

PMID- 18328355
TI  - Is thyroid autoimmunity associated with gestational diabetes mellitus?
AB  - Because inflammatory markers have been associated with incident diabetes
      mellitus, we aimed to evaluate if thyroid peroxidase antibodies (TPOAbs) in early
      pregnancy are predictive of gestational diabetes mellitus (GDM). Six hundred
      nineteen pregnant women without former diabetes mellitus were evaluated for TPOAb
      positivity after booking. A universal GDM screening protocol and the Third
      Workshop-Conference criteria were used for GDM detection. In addition to
      bivariate analysis, multivariate logistic regression models were constructed with
      GDM as the dependent variable and TPOAb positivity as one of the potential
      predictive ones. The rate of TPOAb positivity was 10%; and that of GDM, 6.9%
      (6.8% in women without and 8.1% in women with TPOAb positivity, not significant).
      Thyroid peroxidase antibodies did not enter the multivariate logistic regression
      model to predict GDM that identified the following independent predictive
      variables: maternal age (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.57
      4.0 for the second tertile; OR 2.84, 95% CI 1.16-6.96 for the third tertile),
      prior GDM (OR 9.38, 95% CI 3.34-26.39), and diabetes mellitus in first-degree
      relatives (OR 3.22, 95% CI 1.65-6.27). In conclusion, we have not identified
      TPOAb positivity in early pregnancy as a predictor of GDM.

PMID- 18328356
TI  - Effects of oolong tea on renal sympathetic nerve activity and spontaneous
      hypertension in rats.
AB  - In a previous study, evidence was presented that oolong tea (OT) reduced
      abdominal fat accumulation in diet-induced obese mice. In the study presented
      here, we examined the sympathetic and cardiovascular effects of intraduodenal
      injection of OT in urethane-anesthetized rats and found that it suppressed renal
      sympathetic nerve activity (RSNA) and blood pressure (BP). In addition,
      pretreatment with the histaminergic H3-receptor antagonist thioperamide or
      bilateral subdiaphragmatic vagotomy eliminated the effects of OT on RSNA and BP.
      Furthermore, OT drinking for 14 weeks reduced BP elevation in spontaneously
      hypertensive rats. These results thus suggest that OT may exert its hypotensive
      action through changes in autonomic neurotransmission via an afferent neural
      mechanism. Moreover, we found that intraduodenal injection of decaffeinated OT
      lowered RSNA and BP as well as OT, indicating that substances other than caffeine
      contained in OT may function as effective modulators of RSNA and BP.

PMID- 18328357
TI  - Proglycogen and macroglycogen: artifacts of glycogen extraction?
AB  - Most recent studies on the physiology of proglycogen and macroglycogen in
      skeletal muscles have adopted a homogenization-free acid extraction protocol to
      separate these 2 pools of glycogen. The purposes of this study were to determine
      (a) whether this protocol is suitable; (b) if the acid-insoluble glycogen
      fraction corresponds to proglycogen; and (c) if this fraction accounts for most
      of the changes in muscle glycogen content, irrespective of muscle fiber types.
      Using the rat as our experimental model, this study shows that when the
      conditions of acid extraction are optimized, 52% to 64% of glycogen in rat
      muscles is found as acid-soluble glycogen as opposed to approximately 16% when
      glycogen is extracted using a homogenization-free extraction protocol. Moreover,
      there is no evidence that the acid-insoluble glycogen corresponds to proglycogen
      because gel chromatography of the acid-insoluble and acid-soluble glycogen
      fractions shows similar elution profiles of high-molecular weight glycogen.
      Finally, irrespective of muscle fiber types, the acid-soluble glycogen accounts
      for most of the changes in total muscle glycogen levels during the fasting-to-fed
      transition, whereas the levels of the acid-insoluble glycogen remain stable or
      increase marginally. In conclusion, this study shows that the homogenization-free
      acid extraction of muscle glycogen underestimates the proportion of acid-soluble
      glycogen and that the findings of the studies that have adopted such an
      extraction protocol to examine the physiology of acid-insoluble and acid-soluble
      glycogens require reexamination.

PMID- 18328358
TI  - Association among cigarette smoking, metabolic syndrome, and its individual
      components: the metabolic syndrome study in Taiwan.
AB  - Insulin resistance is a common feature of metabolic syndrome. Smokers are at
      great risk of developing insulin resistance. Theoretically, smoking status should
      be associated with metabolic syndrome. This study aimed to explore the
      association among cigarette smoking, metabolic syndrome, and its individual
      components. Information of participants regarding previous and current diseases,
      family history of disease, smoking habits, alcohol consumption, betel nut
      chewing, and physical activity status were gathered from self-reported nutrition
      and lifestyle questionnaires. The fasting plasma glucose, triglyceride level,
      high-density lipoprotein cholesterol (HDL-C) level, blood pressure, and
      anthropometric indices in each patient were measured. Data of 1146 male subjects
      were analyzed. Individuals who currently smoked had a higher prevalence of
      metabolic syndrome than those who had never smoked and those who had quit
      smoking. The adjusted odds ratios of current smoking amount showed a
      statistically significant dose-dependent association with metabolic syndrome,
      high triglyceride level, and low HDL-C level. Current smokers who smoke > or =20
      pack-years have a significantly increased risk of developing metabolic syndrome,
      high triglyceride level, and low HDL-C level. The higher risk of development of
      metabolic syndrome, high triglyceride level, and low HDL-C level was
      insignificant in former smokers. In conclusion, this community-based study
      supports the view that smoking is associated with metabolic syndrome and its
      individual components. Smoking cessation is beneficial to metabolic syndrome and
      its individual components.

PMID- 18328359
TI  - Carnitine deficiency and L-carnitine supplementation in lysinuric protein
      intolerance.
AB  - The aim of the study was to investigate the prevalence and mechanisms of
      development of carnitine deficiency in patients with lysinuric protein
      intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years
      of age) have been diagnosed with hypocarnitinemia. Their free and total serum
      carnitine levels, acyl carnitine profiles, renal function, diet, and medication
      were compared with the data from 8 age- and sex-matched patients with LPI not
      treated with carnitine supplementation. In patients with LPI, hypocarnitinemia
      was strongly associated with female sex, renal insufficiency, and the use of
      ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of
      muscle weakness, and their symptoms disappeared during carnitine supplementation.
      Oral lysine supplementation did not correct hypocarnitinemia in our patients. The
      patients with LPI are at considerable risk for carnitine deficiency.
      Supplementation of hypocarnitinemic LPI patients with oral L-carnitine improved
      serum total carnitine values, but the ratio of free and total carnitine remained
      subnormal in all supplemented patients except one. Furthermore, decreased ratio
      of free and total serum carnitine was common even in LPI patients with normal
      total serum carnitine concentration.

PMID- 18328360
TI  - Sympathetic-leptin relationship in obesity: effect of weight loss.
AB  - Obese patients have high plasma leptin concentrations that do not induce the
      expected responses on weight regulation, suggesting a leptin resistance in
      obesity. Elevated leptin levels are also thought to be related to a high
      sympathetic nervous system (SNS) activity. This effect could be preserved,
      lowered, or even abolished in obesity. We planned to investigate the possible
      association in a longitudinal study. Ninety-five normotensive healthy women, aged
      40.4 +/- 11.4 years and body mass index of 33.2 +/- 2.3 kg/m(2), were studied.
      Baseline leptin, fat mass, and heart rate variability were measured and included
      in a 6-month longitudinal study. Body composition was measured by dual-energy x
      ray absorption. Time domain heart rate variability, QT dynamicity, and spectral
      components on ambulatory electrocardiographs were analyzed. Dietary advice was
      given by a dietitian to the patient (maximum caloric reduction of 30%), and
      subjects were randomized in 3 treatment groups: sibutramine 10 mg, sibutramine 20
      mg, or placebo. At baseline, low frequencies (LF) and the LF-high frequencies
      (HF) ratio, mainly related to the SNS, were negatively correlated to leptin
      concentration (r = -0.30, P = .002 and r = -0.36, P < .001) and to the leptin-fat
      mass ratio (r = -0.28, P = .004 and r = - 0.33, P = .0007), thus explaining 38%
      of the LF variance and 33% of the LF/HF variance. Diastolic blood pressure was
      also negatively correlated to leptin concentrations (-0.20, P = .04) and to the
      leptin-fat mass ratio (-0.22, P = .022). In contrast, no consistent correlations
      between leptin and the time domain components related to vagal activity were
      observed. At 6 months, after completion of the weight loss program, LF
      significantly decreased (-7.7% +/- 7.9%, P < .001), whereas HF was higher than
      the initial value (+20% +/- 5.2%). The leptin-fat mass ratio remained negatively
      correlated to the LF (r = -0.34, P = .030) and to LF/HF (r = -0.35, P = .021)
      values, explaining 21% of the LF variation. None of the pairwise comparisons
      between the 2 sibutramine groups and the placebo group were statistically
      significant for heart rate variability. High leptin concentration is associated
      with low indexes of cardiac SNS activity and with a lower diastolic blood
      pressure in normotensive obese women. Our results imply therefore that the
      relationship between leptin and the autonomic nervous system is disturbed in
      normotensive obese subjects.

PMID- 18328361
TI  - Tumor necrosis factor-alpha is a marker of familial combined hyperlipidemia,
      independently of metabolic syndrome.
AB  - It is unclear whether an association between familial combined hyperlipidemia
      (FCHL) and inflammatory markers exists, independently of age, sex, body weight,
      insulin resistance, and metabolic syndrome. Serum concentrations of soluble
      vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1,
      interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C
      reactive protein were determined in 135 probands with FCHL and in 146
      normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance
      was evaluated using homeostasis model assessment (HOMA). All inflammatory
      parameters, except interleukin 6, were significantly higher in FCHL according to
      medians or mean comparisons. After adjustment for age, sex, body mass index, and
      HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary
      logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07
      1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and
      95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL,
      respectively) were independent predictors of FCHL status: for TNF-alpha above the
      90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha
      above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The
      independent role of TNF-alpha as predictor of FCHL status was confirmed after
      adjustment for components of the metabolic syndrome (P = .007 and P = .003, for
      TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion,
      among the inflammatory markers most commonly measured, only TNF-alpha was
      associated with FCHL independently of age, sex, body mass index, and HOMA. The
      association of TNF-alpha with FCHL was also independent of the metabolic
      syndrome.

PMID- 18328362
TI  - Nonalcoholic fatty liver disease predicts chronic kidney disease in
      nonhypertensive and nondiabetic Korean men.
AB  - In the absence of significant research, we performed a prospective study to
      examine the association between nonalcoholic fatty liver disease (NAFLD) and
      chronic kidney disease (CKD). The study cohort comprised a total of 8329 healthy
      men, with normal baseline kidney functions and no proteinuria, working in a
      semiconductor manufacturing company and its 13 affiliates. Alcohol intake was
      assessed with a self-reported questionnaire. Biochemical tests for liver and
      metabolic function and abdominal ultrasonography were done. Chronic kidney
      disease was defined as either the presence of proteinuria or a glomerular
      filtration rate (GFR) of <60 mL/min per 1.73 m(2). Cox proportional hazards model
      was used to estimate hazard ratios in the model for CKD. During 26717.1 person
      years of follow-up, 324 men developed CKD. Nonalcoholic fatty liver disease was
      associated with the development of CKD (crude relative risk, 2.18; 95% confidence
      interval [CI], 1.75-2.71); and this relationship remained significant even after
      adjustment for age, GFR, triglyceride, and high-density lipoprotein cholesterol
      (adjusted relative risk [aRR], 1.55; 95% CI, 1.23-1.95). The association between
      NAFLD and incident CKD was evident in the NAFLD group with elevated serum gamma
      glutamyltransferase (GGT) (aRR, 2.31; 95% CI, 1.53-3.50), even after adjustment
      for age, GFR, triglyceride, and high-density lipoprotein cholesterol, but not in
      the NAFLD group without elevated GGT (aRR, 1.09; 95% CI, 0.79-1.50) (P = .008 for
      interaction). To summarize, NAFLD with elevated GGT concentration was associated
      with an increased CKD risk among nondiabetic, nonhypertensive Korean men,
      irrespective of metabolic syndrome.

PMID- 18328363
TI  - Relationships between adipose tissue and cytokine responses to a randomized
      controlled exercise training intervention.
AB  - Adipose-derived cytokines play a prominent role in mediating the metabolic
      consequences of obesity and excess body fat. Given this, we hypothesized that
      alterations in adipose tissue stores incurred with exercise training would be
      reflected in changes in systemic cytokine concentrations. The Studies of Targeted
      Risk Reduction Intervention through Defined Exercise, where pronounced changes in
      adipose tissue stores were observed in the absence of significant changes in
      dietary intake, provided an ideal setting in which to test this hypothesis.
      Participants were randomized to 6 months of inactivity or one of 3 types of
      aerobic exercise training regimens: low-amount-moderate-intensity, low-amount
      vigorous-intensity, and high-amount-vigorous-intensity. Plasma samples were
      collected at baseline and 2 weeks after cessation of 6 months of exercise
      training or inactivity. In 189 participants, concentrations of 17 cytokines were
      measured using Bio-Plex Cytokine Assays (Bio-Rad, Hercules, CA); 10 additional
      cytokines were measured in 60 of these subjects. Of all cytokines tested, the
      only concentration changes that approached statistical significance were those
      for granulocyte monocyte-colony stimulating factor and vascular endothelial
      growth factor, which appeared to increase with training in the low-amount-high
      intensity group only (P < .05 for both cytokines). No response to exercise
      training was noted for any additional cytokine in any of the groups. No
      relationships were observed between changes in cytokine concentrations and
      changes in fat mass or other measures of body habitus. In contradiction to our
      hypothesis, despite significant alterations in body composition, exercise
      training produced limited cytokine responses.

PMID- 18328364
TI  - Physical activity, coronary artery calcium, and bone mineral density in elderly
      men and women: a preliminary investigation.
AB  - The aim of this study was to examine the relationship between cardiorespiratory
      fitness, coronary artery calcification (CAC), and bone mineral density (BMD) in
      older adults. Thirteen highly active, endurance-trained "master athletes" (7 male
      and 6 female) and 12 sedentary (6 male and 6 female) older adults (age 60-78
      years) were recruited for this study. All subjects had CAC measured by electron
      beam computed tomography; BMD assessed by dual-energy X-ray absorptiometry; and
      plasma mineral regulatory proteins, including matrix Gla protein, fetuin-A,
      osteocalcin, osteopontin, and osteoprotegerin, measured by enzyme-linked
      immunosorbent assay. Furthermore, maximal oxygen consumption (VO2max) was
      measured in each subject to provide an objective measure of cardiorespiratory
      fitness. As expected, whole-body BMD was elevated in master athletes compared
      with sedentary adults (1.17 +/- 0.02 vs 1.09 +/- 0.02 g/cm2, P < .05). CAC score
      did not differ between activity groups, but was 8-fold lower in women compared
      with men (P < .05). The CAC score was not correlated with BMD, and there was no
      correlation between CAC and VO2max when both sexes were included in the analysis.
      When the sexes were analyzed separately, several relationships were evident in
      men only. There was a significant inverse correlation between VO2max and the
      number of calcified coronary artery lesions (r = -0.596, P < .05), and the
      correlation between VO2max and logCAC score approached significance (r = -.493, P
      = .08). Furthermore, fetuin-A, a systemic inhibitor of vascular calcification,
      was positively correlated with VO2max in men (r = 0.679, P < .05). These data
      provide preliminary evidence that chronic exercise may simultaneously inhibit CAC
      and increase BMD. The positive correlation between VO2max and plasma fetuin-A
      levels in men indicates a potential mechanism by which exercise may correlate
      negatively with CAC. Additional studies with larger sample sizes will be needed
      to determine if the protective effects of chronic exercise on CAC and BMD are sex
      specific or mediated through common mechanisms such as changes in circulating
      levels of mineral regulatory proteins.

PMID- 18328365
TI  - Otolaryngologic clinics of North America. Preface.

PMID- 18328366
TI  - The unified airway--conceptual framework.
AB  - Substantial evidence exists to support the concept that the respiratory system
      functions as an integrated unit. Pathophysiological processes that involve the
      upper airway generally occur in conjunction with lower airway diseases, and
      diffuse inflammation often affects mucosal surfaces of the middle ear, nose,
      sinuses, and tracheobronchial tree simultaneously. Support for this relationship
      can be found in epidemiological studies, in shared pathophysiological mechanisms,
      and in observed interactive treatment effects. This model and its implications
      are discussed.

PMID- 18328367
TI  - Allergic rhinitis and rhinosinusitis.
AB  - A relationship between allergic rhinitis and acute and chronic rhinosinusitis has
      been postulated for many years. Epidemiologic evidence suggests that such a
      relationship is likely. In addition, evidence of a common pathophysiologic
      mechanism linking these diseases is compelling and continues to evolve. Although
      a clear and definitive causal relationship remains to be elucidated, an
      increasing number of studies support the plausibility of this link. The current
      paradigm of the "unified airway" and evidence to support this model further
      strengthen this link. This article reviews the literature relating allergic
      rhinitis and acute and chronic rhinosinusitis.

PMID- 18328368
TI  - Asthma and rhinitis: comorbidities.
AB  - The connection between asthma and rhinitis is not a new discovery. Significant
      progress has been made in understanding the relationship of these two conditions,
      however, and the implications of the asthma-rhinitis link make it increasingly
      important. Patients who have asthma and rhinitis tend to have more severe disease
      with higher treatment costs. Treatment of rhinitis may improve asthma control,
      and early treatment of allergies may prevent the development of asthma. This
      article more fully explores the epidemiologic, pathophysiologic, and clinical
      relationships between asthma and rhinitis.

PMID- 18328369
TI  - Chronic rhinosinusitis and asthma.
AB  - Based on considerations of the underlying epidemiology, pathophysiology,
      histopathology, clinical relationships and treatment outcomes, the links between
      rhinosinusitis and asthma become evident supporting the unified airway concept.

PMID- 18328370
TI  - The link between allergic rhinitis and chronic otitis media with effusion in
      atopic patients.
AB  - The significant incidence of atopy associated with otitis media with effusion
      (OME) has suggested a role of allergy in the pathogenesis of OME. Analysis of
      inflammatory mediators indicates that the mucosa of the middle ear can respond to
      antigen in the same way as does the mucosa of the lower respiratory tract. Recent
      characterization of the mucosa and effusion from atopic patients with OME reveals
      a Th2 cytokine and cellular profiles consistent with an allergic response,
      supporting the role of allergy in OME. In addition, animal studies demonstrate
      that inhibiting characteristic allergy cytokines can prevent the production of
      middle ear effusion. As the understanding of allergy and its role in the
      inflammation of OME continues to deepen, this will introduce focused treatments
      of OME in the atopic population.

PMID- 18328371
TI  - Allergic rhinitis--history and presentation.
AB  - Allergic rhinitis is a common disorder that results from a complex interaction of
      environmental and genetic causes. This disorder has a tremendous impact on the
      quality of life and on health care expenditures, as evidenced by a large loss of
      worker productivity. Care must be taken to promptly diagnose patients with this
      condition, evaluate them for associated conditions, and begin appropriate
      management to reduce its impact on the individual and the health care system.
      Allergic rhinitis represents only a component of the spectrum of inflammatory
      diseases involving the unified airway.

PMID- 18328372
TI  - Allergic rhinitis--current approaches to skin and in vitro testing.
AB  - This article discusses the currently available techniques used for the diagnosis
      of IgE-mediated upper respiratory allergy. These methods are necessary to confirm
      the presence and the intensity of allergy in an effort to select patients for
      immunotherapy and to dose immunotherapy properly. Specific techniques discussed
      include epicutaneous and intradermal skin tests and in vitro tests designed to
      measure antigen-specific IgE antibody.

PMID- 18328373
TI  - Allergic rhinitis--current pharmacotherapy.
AB  - The use of pharmacotherapy for allergic rhinitis remains a central strategy in
      the integrated treatment of the patient. The most appropriate medical therapy
      depends upon the nature of specific rhinitis symptoms, patient tolerance to and
      preference for certain classes of medications, and response to treatment. Through
      an appreciation of these various physiological mechanisms, the physician can
      select the treatment option or options that will be most likely to effectively
      manage symptoms.

PMID- 18328374
TI  - Injection and sublingual immunotherapy in the management of allergies affecting
      the unified airway.
AB  - The spectrum of allergic disease involves both the upper and lower airways.
      Immunotherapy has been shown to produce immunologic changes that can result in
      the improvement of allergic diseases. Numerous clinical trials have demonstrated
      the effectiveness of injection and sublingual immunotherapy in the treatment of
      rhinitis and asthma. Recent data suggest that immunotherapy may have a role in
      preventing the development of new sensitizations or in decreasing the progression
      of allergic disease from rhinitis to asthma. Models of immunotherapy may
      therefore transition from symptom-relieving treatments to preventive
      methodologies for the management of allergic disease.

PMID- 18328375
TI  - Asthma history and presentation.
AB  - Asthma is suspected from a history of key symptoms, including cough, wheezing,
      dyspnea, chest tightness, and increased mucus production. A positive family or
      personal history of atopic diseases and diseases that are comorbid with asthma,
      such as allergic rhinitis and rhinosinusitis, is also important. The differential
      diagnosis of asthma is broad and includes potentially life-threatening diseases.
      Pediatric asthma and psychiatric mimics require special attention to prevent
      misdiagnosis. Differentiating asthma from these other disease states by history
      alone is not always possible. Because accurate diagnosis is critical to
      successful treatment, objective testing by spirometry and methacholine challenge
      should be employed.

PMID- 18328376
TI  - Introduction to pulmonary function.
AB  - Asthma is a dynamic and complex inflammatory disease. Recent research suggests
      that it is a manifestation of a systemic disorder of the entire respiratory
      system including both upper and lower airways. The diagnosis of asthma can be
      made based on clinical history, physical findings, and pulmonary function tests
      such as spirometry. In children, spirometry may be difficult; therefore, diurnal
      changes in peak expiratory flow rate can be used instead to assist in the
      diagnosis of asthma. Increasing the use of objective pulmonary measures will help
      better identify and monitor treatment of lower respiratory inflammatory disease.

PMID- 18328377
TI  - Asthma: guidelines-based control and management.
AB  - Guidelines-based management of the patient with asthma allows maximal levels of
      function with few adverse effects. A flexible approach to therapy that emphasizes
      an ongoing partnership between the patient and physician allows optimal
      communication, facilitating treatment adherence and maximal levels of control.
      Through assessment of the patient's initial severity of disease and an evaluation
      of the patient's ongoing level of control, appropriate medical therapy can be
      initiated and level of therapy can be modified based on the patient's response.
      Patient education, environmental control strategies, and proper use of
      medications are vital in achieving maximal benefit in asthma management.
      Excellent asthma control is possible and should be a goal of both physicians and
      patients.

PMID- 18328378
TI  - Environmental controls of allergies.
AB  - Environmental controls of allergy remain a cornerstone in the management of
      patients who have allergic rhinitis. In the past, recommendations for
      environmental controls were based on common sense and the demonstration that
      certain methods of environmental control reduce antigen quantity. Reduction of
      antigen quantity is, however, only an indirect measure of whether an
      environmental control strategy actually reduces allergic symptoms. This article
      details current recommendations for reducing antigen exposure based on specific
      antigen sensitivities. Strategies for reduction of indoor inhalant allergens-dust
      mites, cockroach, molds, and house pet danders-are presented, as well as
      techniques for reducing exposure to outdoor inhalant allergens.

PMID- 18328379
TI  - Laryngitis: types, causes, and treatments.
AB  - Inflammatory processes that affect the unified airway can concurrently exert
      significant influence on the larynx and surrounding mucosal surfaces. Laryngeal
      inflammation can be present secondary to direct effects of irritants, toxins, and
      antigens, but can also involve mechanical and infectious effects as well as
      secondary inflammation from behavioral mechanisms. This review examines laryngeal
      inflammation in the context of the unified airway and discusses pathophysiologic
      mechanisms that are central to the development of acute and chronic laryngitis.

PMID- 18328380
TI  - Laryngitis--diagnosis and management.
AB  - Laryngeal inflammation includes a broad spectrum of pathologies, from infectious
      processes that need to be managed as airway emergencies, to indolent diseases
      that mimic head and neck cancer. The importance of a thorough history cannot be
      emphasized enough as it is the most important step toward developing a
      differential diagnosis. Vocal pathologies often have a noticeable impact on a
      person's quality of life and daily activities; therefore, it is key to counsel
      patients on the course of the disease process. Treatment of specific pathologies
      depends on the causative pathogen or etiology, as well as the age, vocal demands,
      and clinical characteristics of the individual.

PMID- 18328381
TI  - Baby, it's cold inside: the past offers lessons about the future of hypothermia.

PMID- 18328391
TI  - Shaping EMS becoming a part of the political process.

PMID- 18328392
TI  - The few, the proud: how to motivate your employees marine-style.

PMID- 18328393
TI  - C'meah, Chu-Chu: controlling patients' belongings.

PMID- 18328394
TI  - Heart rate: 310. Identifying & treating a rapid wide complex tachycardia.

PMID- 18328395
TI  - Is my patient faking? The ethical, objective way to react in the field without
      ammonia.

PMID- 18328398
TI  - Relying on your H&P. Are we losing the art of clinical medicine to technology?

PMID- 18328399
TI  - Prehospital Fibrinolysis in concert with rapid PCI. Clinical trial shows
      promising results for use of clot-dissolving agents in the field.

PMID- 18328400
TI  - The new hemophiliacs. Providing care for patients with pharmacologically altered
      clotting functions.

PMID- 18328401
TI  - Beyond the battlefield. The use of hemostatic dressings in civilian EMS.

PMID- 18328402
TI  - Focus on RSI. Does training in the or create an optimal RSI program?

PMID- 18328403
TI  - Words from the wise. Female EMS leaders share their perspectives.

PMID- 18328404
TI  - P.E.T. project prehospital evaluation technique. Evaluating the performance of
      your prehospital personnel.

PMID- 18328405
TI  - Ryan White notification law repealed. The deletion of emergency-response
      provisions demands attention.

PMID- 18328408
TI  - Safety and nutritional assessment of GM plants and derived food and feed: the
      role of animal feeding trials.
AB  - In this report the various elements of the safety and nutritional assessment
      procedure for genetically modified (GM) plant derived food and feed are
      discussed, in particular the potential and limitations of animal feeding trials
      for the safety and nutritional testing of whole GM food and feed. The general
      principles for the risk assessment of GM plants and derived food and feed are
      followed, as described in the EFSA guidance document of the EFSA Scientific Panel
      on Genetically Modified Organisms. In Section 1 the mandate, scope and general
      principles for risk assessment of GM plant derived food and feed are discussed.
      Products under consideration are food and feed derived from GM plants, such as
      maize, soybeans, oilseed rape and cotton, modified through the introduction of
      one or more genes coding for agronomic input traits like herbicide tolerance
      and/or insect resistance. Furthermore GM plant derived food and feed, which have
      been obtained through extensive genetic modifications targeted at specific
      alterations of metabolic pathways leading to improved nutritional and/or health
      characteristics, such as rice containing beta-carotene, soybeans with enhanced
      oleic acid content, or tomato with increased concentration of flavonoids, are
      considered. The safety assessment of GM plants and derived food and feed follows
      a comparative approach, i.e. the food and feed are compared with their non-GM
      counterparts in order to identify intended and unintended (unexpected)
      differences which subsequently are assessed with respect to their potential
      impact on the environment, safety for humans and animals, and nutritional
      quality. Key elements of the assessment procedure are the molecular,
      compositional, phenotypic and agronomic analysis in order to identify
      similarities and differences between the GM plant and its near isogenic
      counterpart. The safety assessment is focussed on (i) the presence and
      characteristics of newly expressed proteins and other new constituents and
      possible changes in the level of natural constituents beyond normal variation,
      and on the characteristics of the GM food and feed, and (ii) the possible
      occurrence of unintended (unexpected) effects in GM plants due to genetic
      modification. In order to identify these effects a comparative phenotypic and
      molecular analysis of the GM plant and its near isogenic counterpart is carried
      out, in parallel with a targeted analysis of single specific compounds, which
      represent important metabolic pathways in the plant like macro and micro
      nutrients, known anti-nutrients and toxins. Significant differences may be
      indicative of the occurrence of unintended effects, which require further
      investigation. Section 2 provides an overview of studies performed for the safety
      and nutritional assessment of whole food and feed. Extensive experience has been
      built up in recent decades from the safety and nutritional testing in animals of
      irradiated foods, novel foods and fruit and vegetables. These approaches are also
      relevant for the safety and nutritional testing of whole GM food and feed. Many
      feeding trials have been reported in which GM foods like maize, potatoes, rice,
      soybeans and tomatoes have been fed to rats or mice for prolonged periods, and
      parameters such as body weight, feed consumption, blood chemistry, organ weights,
      histopathology etc have been measured. The food and feed under investigation were
      derived from GM plants with improved agronomic characteristics like herbicide
      tolerance and/or insect resistance. The majority of these experiments did not
      indicate clinical effects or histopathological abnormalities in organs or tissues
      of exposed animals. In some cases adverse effects were noted, which were
      difficult to interpret due to shortcomings in the studies. Many studies have also
      been carried out with feed derived from GM plants with agronomic input traits in
      target animal species to assess the nutritive value of the feed and their
      performance potential. Studies in sheep, pigs, broilers, lactating dairy cows,
      and fish, comparing the in vivo bioavailability of nutrients from a range of GM
      plants with their near isogenic counterpart and commercial varieties, showed that
      they were comparable with those for near isogenic non-GM lines and commercial
      varieties. In Section 3 toxicological in vivo, in silico, and in vitro test
      methods are discussed which may be applied for the safety and nutritional
      assessment of specific compounds present in food and feed or of whole food and
      feed derived from GM plants. Moreover the purpose, potential and limitations of
      the 90-day rodent feeding trial for the safety and nutritional testing of whole
      food and feed have been examined. Methods for single and repeated dose toxicity
      testing, reproductive and developmental toxicity testing and immunotoxicity
      testing, as described in OECD guideline tests for single well-defined chemicals
      are discussed and considered to be adequate for the safety testing of single
      substances including new products in GM food and feed. Various in silico and in
      vitro methods may contribute to the safety assessment of GM plant derived food
      and feed and components thereof, like (i) in silico searches for sequence
      homology and/or structural similarity of novel proteins or their degradation
      products to known toxic or allergenic proteins, (ii) simulated gastric and
      intestinal fluids in order to study the digestive stability of newly expressed
      proteins and in vitro systems for analysis of the stability of the novel protein
      under heat or other processing conditions, and (iii) in vitro genotoxicity test
      methods that screen for point mutations, chromosomal aberrations and DNA
      damage/repair. The current performance of the safety assessment of whole foods is
      mainly based on the protocols for low-molecular-weight chemicals such as
      pharmaceuticals, industrial chemicals, pesticides, food additives and
      contaminants. However without adaptation, these protocols have limitations for
      testing of whole food and feed. This primarily results from the fact that defined
      single substances can be dosed to laboratory animals at very large multiples of
      the expected human exposure, thus giving a large margin of safety. In contrast
      foodstuffs are bulky, lead to satiation and can only be included in the diet at
      much lower multiples of expected human intakes. When testing whole foods, the
      possible highest concentration of the GM food and feed in the laboratory animal
      diet may be limited because of nutritional imbalance of the diet, or by the
      presence of compounds with a known toxicological profile. The aim of the 90-days
      rodent feeding study with the whole GM food and feed is to assess potential
      unintended effects of toxicological and/or nutritional relevance and to establish
      whether the GM food and feed is as safe and nutritious as its traditional
      comparator rather than determining qualitative and quantitative intrinsic
      toxicity of defined food constituents. The design of the study should be adapted
      from the OECD 90-day rodent toxicity study. The precise study design has to take
      into account the nature of the food and feed and the characteristics of the new
      trait(s) and their intended role in the GM food and feed. A 90-day animal feeding
      trial has a large capacity (sensitivity and specificity) to detect potential
      toxicological effects of single well defined compounds. This can be concluded
      from data reported on the toxicology of a wide range of industrial chemicals,
      pharmaceuticals, food substances, environmental, and agricultural chemicals. It
      is possible to model the sensitivity of the rat subchronic feeding study for the
      detection of hypothetically increased amount of compounds such as anti-nutrients,
      toxicants or secondary metabolites. With respect to the detection of potential
      unintended effects in whole GM food and feed, it is unlikely that substances
      present in small amounts and with a low toxic potential will result in any
      observable (unintended) effects in a 90-day rodent feeding study, as they would
      be below the no-observed-effect-level and thus of unlikely impact to human health
      at normal intake levels. Laboratory animal feeding studies of 90-days duration
      appear to be sufficient to pick up adverse effects of diverse compounds that
      would also give adverse effects after chronic exposure. This conclusion is based
      on literature data from studies investigating whether toxicological effects are
      adequately identified in 3-month subchronic studies in rodents, by comparing
      findings at 3 and 24 months for a range of different chemicals. The 90-day rodent
      feeding study is not designed to detect effects on reproduction or development
      other than effects on adult reproductive organ weights and histopathology.
      Analyses of available data indicate that, for a wide range of substances,
      reproductive and developmental effects are not potentially more sensitive
      endpoints than those examined in subchronic toxicity tests. Should there be
      structural alerts for reproductive/developmental effects or other indications
      from data available on a GM food and feed, then these tests should be considered.
      By relating the estimated daily intake, or theoretical maximum daily intake per
      capita for a given whole food (or the sum of its individual commercial
      constituents) to that consumed on average per rat per day in the subchronic 90
      day feeding study, it is possible to establish the margin of exposure (safety
      margin) for consumers. Results obtained from testing GM food and feed in rodents
      indicate that large (at least 100-fold) 'safety' margins exist between animal
      exposure levels without observed adverse effects and estimated human daily
      intake. Results of feeding studies with feed derived from GM plants with improved
      agronomic properties, carried out in a wide range of livestock species, are
      discussed. The studies did not show any biologically relevant differences in the
      parameters tested between control and test animals. (ABSTRACT TRUNCATED)

PMID- 18328409
TI  - Nutrient intake from habitual oral diet in patients with severe short bowel
      syndrome living in the southeastern United States.
AB  - OBJECTIVES: Little data are published on the habitual home oral diet of patients
      with short bowel syndrome (SBS). METHODS: We assessed nutrient intake from oral
      food and beverages in 19 stable patients with severe SBS who live in the
      southeastern United States. Intestinal absorption of energy, fat, nitrogen (N),
      and carbohydrate (CHO) was determined in a metabolic ward. RESULTS: We studied 12
      women and 7 men, age 48 +/- 3 y of age (mean +/- SE) receiving parenteral
      nutrition for 31 +/- 8 mo following massive small bowel resection (118 +/- 25 cm
      residual small bowel). The patients demonstrated severe malabsorption of energy
      (59 +/- 3% of oral intake), fat (41 +/- 5%), N (42 +/- 5%) and CHO (76 +/- 3%).
      Oral energy intake was 2656 +/- 242 kcal/d (39 +/- 3 kcal/kg/d) and oral protein
      intake was 1.4 +/- 0.1 g/kg/d. Food/beverage intake constituted 49 +/- 4% of
      total (enteral plus parenteral) daily fluid intake, 66 +/- 4% of total daily kcal
      and 58 +/- 5% of total daily N intake. Oral fat intake averaged 92 +/- 11 g/day (
      approximately 35% of total oral energy). Oral fluid intake averaged 2712 +/- 240
      ml/d, primarily from water, soft drinks, sweet tea and coffee. Simple sugars
      comprised 42 +/- 3% of oral CHO intake. Usual dietary intake of multiple
      micronutrients were below the Recommended Dietary Allowances (RDA) in a large
      percentage of patients: vitamin A (47%), vitamin D (79%), vitamin E (79%),
      vitamin K (63%), thiamine (42%), vitamin B6 (68%), vitamin B12 (11%), vitamin C
      (58%), folate (37%), iron (37%), calcium (63%), magnesium (79%) and zinc (68%).
      Only seven patients (37%) were taking oral multivitamin-mineral supplements and
      only six subjects (32%) were taking oral iron and calcium supplements,
      respectively. CONCLUSION: In these SBS patients, an oral diet provided a
      significant proportion of daily nutrient intake. The types of foods and fluids
      consumed are likely to worsen malabsorption and thus increase PN requirements.
      Oral intake of essential micronutrients was very low in a significant proportion
      of these individuals.

PMID- 18328410
TI  - Effects of milk ingestion on prolonged exercise capacity in young, healthy men.
AB  - OBJECTIVE: The effects of fluid intake during prolonged exercise have been
      extensively studied but at present there exists little information on the effects
      of milk-based drinks on the response to prolonged exercise. Thus, the purpose of
      this study was to investigate the effects of milk-based drinks on exercise
      capacity. METHODS: Eight healthy males (age 24 +/- 4 y, height 1.76 +/- 0.04 m,
      mass 68.9 +/- 9.5 kg, body fat 12.5 +/- 2.4%, peak oxygen consumption 4.3 +/- 0.6
      L/min) exercised to volitional exhaustion at 70% peak oxygen consumption on four
      occasions. Subjects ingested 1.5 mL/kg body mass of plain water, a carbohydrate
      electrolyte solution, low-fat (0.1%) milk, or low-fat (0.1%) milk with added
      glucose before and every 10 min during exercise. The effect of the drink on
      exercise capacity and the cardiovascular, metabolic, and thermoregulatory
      responses to prolonged exercise were examined. RESULTS: Exercise time to
      exhaustion was not significantly influenced by the drink ingested (P = 0.19), but
      there was a tendency for subjects to exercise longer when the carbohydrate
      electrolyte (110.6, range 82.0-222.7 min), milk (103.3, range 85.7-228.5 min), or
      milk plus glucose (102.8, range 74.3-167.1 min) was ingested compared with water
      (93.3, range 82.4-192.3 min). The solution ingested did not influence the
      cardiovascular, metabolic, or thermoregulatory response to exercise. CONCLUSION:
      The results of this study suggest that although the low-fat milk-based fluids did
      not enhance exercise capacity over that seen with the ingestion of plain water,
      the effect was comparable to that observed with a carbohydrate-electrolyte
      beverage.

PMID- 18328411
TI  - Protein synthesis and memory. Introduction.

PMID- 18328412
TI  - External fixation for lower limb salvage. Preface.

PMID- 18328413
TI  - Simple solutions for difficult problems: a beginner's guide to ring fixation.
AB  - Ring external fixation is a surgical method for leg lengthening and deformity
      correction. It allows limited surgical exposure and dissection and can be
      tolerated for prolonged periods as compared to threaded uniplanar or multiplanar
      constructs. Because of the complexity in application and adjustment of the frame
      constructs, most orthopedic surgeons avoid using these devices. Surgeons are
      advised to apply these techniques initially to less complicated clinical
      situations, expanding application with comfort and proficiency. This discussion
      introduces ring fixation and provides guidelines for simple applications.
      Experience with these simple applications allows surgeons to expand their
      spectrum of proficiency and provides alternatives for solving complex clinical
      problems.

PMID- 18328414
TI  - The basics of ring external fixator application and care.
AB  - The advantages of ring external fixation for correction of complex deformities of
      the foot and ankle include the ability to correct severe deformity, perform
      gradual correction, modify treatment during correction, and minimize
      neurovascular damage. External fixation can provide opportunities to operate on
      scarred and contracted tissues, preserve joints and joint function, maintain or
      gain foot length, and allow weight bearing during treatment.

PMID- 18328415
TI  - Salvage of pilon fracture nonunion and infection with circular tensioned wire
      fixation.
AB  - Nonunion, malunion, and infection are complications encountered when treating
      fractures of the distal tibia extending into the joint surface. There is rank
      order of severity of those complications extending from a varus collapse of the
      medial column of the distal tibia with a reduced joint surface to an infected
      nonunion with destruction of the joint surface, segmental bone loss, and damaged
      soft tissue envelope. Malunion and malposition of nonunion of the distal tibia
      have a combination of angular deformity, translation, rotational malalignment,
      and shortening. These deformities require correction in the reconstruction and
      there are multiple technique pathways to achieving a successful reconstruction.

PMID- 18328416
TI  - Perioperative planning for two- and three-plane deformities.
AB  - Primary multiplanar external fixation is efficacious for a variety of fractures
      and may avoid a salvage situation. Complex deformity in conjunction with
      fractures, nonunions, and malunions can be measured and corrected with the Taylor
      Spatial Frame using the chronic and especially the total residual correction
      methods. Distal referencing-characterizing a deformed proximal fragment with
      respect to a normal distal fragment-is very useful in most lower-limb salvage
      cases. Corrections may be performed in stages using way points, and additional
      total residual corrections may be performed as needed. The same frame and
      analysis used for gradual correction may be used in conjunction with
      intramedullary nailing or plating in some cases.

PMID- 18328417
TI  - Hindfoot salvage with external fixation.
AB  - Hindfoot salvage procedures by definition present circumstances requiring
      extraordinary measures to prevent or limit damage or destruction. Although this
      technique is used at some centers as the only means of correcting and fixating
      foot and ankle deformities, it is an expensive procedure. Other available methods
      may be more expeditious depending on the circumstances. However, the benefits of
      external fixation in certain circumstances are invaluable. Circular frame
      external fixators are important tool for the foot and ankle surgeon.

PMID- 18328418
TI  - External fixators as an adjunct to wound healing.
AB  - Complex foot and ankle wounds present multiple challenges for the reconstructive
      surgeon. Soft tissue deficits must be closed to protect underlying structures
      from infection and to provide a stable environment for healing. Surgical options
      commonly used include healing by secondary intention, local flap closure, skin
      grafts, pedicled flaps, and free tissue transfer. Despite a surgeon's best
      operative efforts, these strategies may fail because of postoperative shear
      forces created by premature joint motion or pressure (either weight bearing or
      decubitus). In the properly selected patient population, external fixators serve
      as an indispensable adjunct to wound healing by providing temporary offloading or
      immobilization of joints.

PMID- 18328419
TI  - Charcot salvage of the foot and ankle using external fixation.
AB  - This article details the advantages of external fixation for salvage of the
      Charcot foot and ankle. Preoperative evaluation, postoperative care, and surgical
      technique for external fixation are described. The literature on the
      effectiveness of this technique in the Charcot foot and ankle is reviewed.

PMID- 18328420
TI  - A catalytic role for proangiogenic marrow-derived cells in tumor
      neovascularization.
AB  - Small numbers of proangiogenic bone marrow-derived cells (BMDCs) can play pivotal
      roles in tumor progression. In this issue of Cancer Cell, two papers, utilizing
      different tumor angiogenesis models, both find that activated MMP-9 delivered by
      BMDCs modulates neovessel remodeling, thereby promoting tumor growth. The changes
      in microvascular anatomy induced by MMP-9-expressing BMDCs are strikingly
      different between the preirradiated tumor vascular bed model employed by Ahn and
      Brown and the invasive glioblastoma model utilized by Du et al., likely mirroring
      the complexity of the real tumor microenvironment and the intricacy of roles of
      different BMDC populations in mediating tumor neoangiogenesis.

PMID- 18328421
TI  - Staying the distance: avoiding the proteasomal trap.
AB  - There are a multitude of nuclear receptor coactivators, and as a result,
      individual constituents of activation complexes are often overlooked when
      studying the specific actions of hormone signaling pathways. Specificity is
      typically associated with the receptor and its cognate ligand. However, SRC-3 has
      distinguished itself by persistent association with cell growth. In the February
      29 issue of Molecular Cell, Yi et al. demonstrate that estrogen-induced
      posttranslational modulation of SRC-3 by atypical PKC shields it from proteasomal
      degradation, facilitating increased estrogenic gene activity. This process may
      have important implications in different types of hormone-sensitive tumors,
      particularly breast cancer.

PMID- 18328422
TI  - Learning the ABCs of melanoma-initiating cells.
AB  - Tumor stem or initiating cells have been proposed to exist for melanoma. Stem
      like cells have been propagated from melanoma cell lines and specimens.
      Additionally, classical stem cell markers, including ABCG2 and CD133, have been
      identified in clinical melanomas. However, definitive markers for the
      purification and further characterization of melanoma-initiating cells remained
      elusive. Recently, Schatton et al. provided solid evidence that the doxorubicin
      resistant ATP-binding cassette transporter ABCB5 marks primitive cells capable of
      recapitulating melanomas in xenotransplantation models. The identification of
      melanoma-initiating cells has far-reaching implications, as new therapeutic
      strategies can be envisioned that specifically target these cells.

PMID- 18328423
TI  - The emerging role of the hippo pathway in cell contact inhibition, organ size
      control, and cancer development in mammals.
AB  - The Hippo pathway defined originally in Drosophila melanogaster is conserved in
      mammals. The fly core components Hippo, Sav, Wts, and Mats are conserved in
      mammals as Mst1/2, WW45, LATS1/2, and Mob1. The pathway impinges on
      transcriptional coactivator Yorkie in fly and YAP in mammals to coordinate cell
      proliferation and apoptosis. Several recent publications establish that the
      pathway is one major conserved mechanism governing cell contact inhibition, organ
      size control, and cancer development. This advance opens new vistas in exploring
      fundamental mechanisms in cell and developmental biology and offers potential
      targets to interfere with cancer development.

PMID- 18328424
TI  - Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for
      angiogenesis: role of bone marrow-derived myelomonocytic cells.
AB  - Tumor vasculature is derived from sprouting of local vessels (angiogenesis) and
      bone marrow (BM)-derived circulating cells (vasculogenesis). By using a model
      system of transplanting tumors into an irradiated normal tissue to prevent
      angiogenesis, we found that tumors were unable to grow in matrix
      metalloproteinase-9 (MMP-9) knockout mice, but tumor growth could be restored by
      transplantation of wild-type BM. Endothelial progenitor cells did not contribute
      significantly to this process. Rather, CD11b-positive myelomonocytic cells from
      the transplanted BM were responsible for tumor growth and the development of
      immature blood vessels in MMP-9 knockout mice receiving wild-type BM. Our results
      suggest that MMP-9 could be an important target for adjunct therapy to enhance
      the response of tumors to radiotherapy.

PMID- 18328425
TI  - HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory
      cells to regulate tumor angiogenesis and invasion.
AB  - Development of hypoxic regions is an indicator of poor prognosis in many tumors.
      Here, we demonstrate that HIF1alpha, the direct effector of hypoxia, partly
      through increases in SDF1alpha, induces recruitment of bone marrow-derived CD45+
      myeloid cells containing Tie2+, VEGFR1+, CD11b+, and F4/80+ subpopulations, as
      well as endothelial and pericyte progenitor cells to promote neovascularization
      in glioblastoma. MMP-9 activity of bone marrow-derived CD45+ cells is essential
      and sufficient to initiate angiogenesis by increasing VEGF bioavailability. In
      the absence of HIF1alpha, SDF1alpha levels decrease, and fewer BM-derived cells
      are recruited to the tumors, decreasing MMP-9 and mobilization of VEGF. VEGF also
      directly regulates tumor cell invasiveness. When VEGF activity is impaired, tumor
      cells invade deep into the brain in the perivascular compartment.

PMID- 18328426
TI  - The inhibition of tumor cell intravasation and subsequent metastasis via
      regulation of in vivo tumor cell motility by the tetraspanin CD151.
AB  - In vivo tumor cell migration through integrin-dependent pathways is key to the
      metastatic behavior of malignant cells. Using quantitative in vivo assays and
      intravital imaging, we assessed the impact of cell migration, regulated by the
      integrin-associated tetraspanin CD151, on spontaneous human tumor cell
      metastasis. We demonstrate that promoting immobility through a CD151-specific
      metastasis blocking mAb prevents tumor cell dissemination by inhibiting
      intravasation without affecting primary tumor growth, tumor cell arrest,
      extravasation, or growth at the secondary site. In vivo, this loss of migration
      is the result of enhanced tumor cell-matrix interactions, promoted by CD151,
      which prevent dissociation by individual cells and leads to a subsequent
      inhibition of invasion and intravasation at the site of the primary tumor.

PMID- 18328427
TI  - Yes and PI3K bind CD95 to signal invasion of glioblastoma.
AB  - Invasion of surrounding brain tissue by isolated tumor cells represents one of
      the main obstacles to a curative therapy of glioblastoma multiforme. Here we
      unravel a mechanism regulating glioma infiltration. Tumor interaction with the
      surrounding brain tissue induces CD95 Ligand expression. Binding of CD95 Ligand
      to CD95 on glioblastoma cells recruits the Src family member Yes and the p85
      subunit of phosphatidylinositol 3-kinase to CD95, which signal invasion via the
      glycogen synthase kinase 3-beta pathway and subsequent expression of matrix
      metalloproteinases. In a murine syngeneic model of intracranial GBM,
      neutralization of CD95 activity dramatically reduced the number of invading
      cells. Our results uncover CD95 as an activator of PI3K and, most importantly, as
      a crucial trigger of basal invasion of glioblastoma in vivo.

PMID- 18328428
TI  - Transient inhibition of the Hedgehog pathway in young mice causes permanent
      defects in bone structure.
AB  - The Hedgehog (Hh) pathway plays critical roles in normal development and in
      tumorigenesis. We generated Gli-luciferase transgenic mice to evaluate the Smo
      inhibitor, HhAntag, by whole animal functional imaging. HhAntag rapidly reduced
      systemic luciferase activity in 10- to 14-day-old mice following oral dosing.
      Although pathway activity was restored 2 days after drug removal, brief
      inhibition caused permanent defects in bone growth. HhAntag inhibited
      proliferation and promoted differentiation of chondrocytes, leading to dramatic
      expansion of the hypertrophic zone. After drug removal, osteoblasts invaded the
      cartilage plate, mineralization occurred, and there was premature fusion of the
      growth plate resulting in permanent disruption of bone epiphyses.

PMID- 18328429
TI  - A conditional mouse model for malignant mesothelioma.
AB  - Malignant mesothelioma is a devastating disease that has been associated with
      loss of Neurofibromatosis type 2 (NF2) and genetic lesions affecting RB and P53
      pathways. We introduced similar lesions in the mesothelial lining of the thoracic
      cavity of mice. Mesothelioma developed at high incidence in Nf2;Ink4a/Arf and
      Nf2;p53 conditional knockout mice with median survival times of approximately 30
      and 20 weeks, respectively. Murine mesothelioma closely mimicked human malignant
      mesothelioma. Conditional Nf2;Ink4a/Arf mice showed increased pleural invasion
      compared to conditional Nf2;p53 mice. Interestingly, upon Ink4a loss in the
      latter mice median survival was significantly reduced and all tumors were highly
      invasive, suggesting that Ink4a loss substantially contributes to the poor
      clinical outcome of malignant mesothelioma.

PMID- 18328430
TI  - E2F1-regulated microRNAs impair TGFbeta-dependent cell-cycle arrest and apoptosis
      in gastric cancer.
AB  - Deregulation of E2F1 activity and resistance to TGFbeta are hallmarks of gastric
      cancer. MicroRNAs (miRNAs) are small noncoding RNAs frequently misregulated in
      human malignancies. Here we provide evidence that the miR-106b-25 cluster,
      upregulated in a subset of human gastric tumors, is activated by E2F1 in parallel
      with its host gene, Mcm7. In turn, miR-106b and miR-93 regulate E2F1 expression,
      establishing a miRNA-directed negative feedback loop. Furthermore, upregulation
      of these miRNAs impairs the TGFbeta tumor suppressor pathway, interfering with
      the expression of CDKN1A (p21(Waf1/Cip1)) and BCL2L11 (Bim). Together, these
      results suggest that the miR-106b-25 cluster is involved in E2F1
      posttranscriptional regulation and may play a key role in the development of
      TGFbeta resistance in gastric cancer.

PMID- 18328433
TI  - Photodynamic therapy: standard of care for palliation of cholangiocarcinoma?

PMID- 18328434
TI  - Chronic hepatitis B: preventing, detecting, and managing viral resistance.
AB  - Licensed oral agents for antiviral therapy in patients with chronic hepatitis B
      virus (HBV) infection include lamivudine, adefovir, entecavir, and telbivudine.
      Emtricitabine, tenofovir, and the combination of tenofovir plus emtricitabine in
      1 tablet, which are licensed for the treatment of human immunodeficiency virus
      infection, are additional off-label options for treating HBV infection.
      Preventing HBV antiviral drug resistance to nucleoside/nucleotide analogues and
      appropriate management when resistance occurs has become a major focus in the
      management of chronic hepatitis B. HBV antiviral drug resistance may be best
      prevented by using an agent or combination of agents with a high genetic barrier
      to resistance, and 2 potent nucleoside and nucleotide drugs with different
      resistance profiles may prove to be the optimal first-line treatment for chronic
      hepatitis B. Frequent assessment of quantitative serum HBV DNA remains the best
      approach to early detection of resistance, and antiviral therapy should be
      modified as soon as resistance is detected. Results from several clinical trials
      have shown that the addition or substitution of newer antiviral agents can
      restore suppression of viral replication, normalize alanine aminotransferase
      levels, and reverse histologic progression in patients with resistance to
      lamivudine, but little information exists regarding the long-term benefits of
      second-line treatment regimens. Despite the substantial advances in treatment
      made to date, new agents with novel viral targets will be needed for patients who
      ultimately may fail second- or third-line therapy.

PMID- 18328435
TI  - Pancreatic cancer: a review of the evidence on causation.
AB  - Pancreatic cancer kills more than 250,000 people each year worldwide and has a
      poor prognosis. The aim of this article is to critically review the epidemiologic
      evidence for exposures that may either increase or decrease the risk. A Medline
      search was performed for epidemiologic studies and reviews published up to April
      2007. Consistent evidence of a positive association was found for family history
      and cigarette smoking. Many studies documented a positive association with
      diabetes mellitus and chronic pancreatitis, although the etiologic mechanisms are
      unclear. Other associations were detected, but the results were either
      inconsistent or from few studies. These included positive associations with red
      meat, sugar, fat, body mass index, gallstones, and Helicobacter pylori, and
      protective effects of increasing parity, dietary folate, aspirin, and statins.
      There was no evidence linking alcohol or coffee consumption with an increased
      risk of pancreatic cancer. The associations with many exposures need to be
      clarified from further epidemiologic work in which there is both precise
      measurement of risk factors, adjustment for potential confounders, and, for
      dietary studies, information recorded on the method of food preparation and
      pattern of consumption. Such work is important to reduce the incidence of this
      fatal disease.

PMID- 18328436
TI  - Computerized tomography enterography and its role in small-bowel imaging.
AB  - Computerized tomography enterography is being adopted rapidly by many
      institutions as the primary technique used to image the small bowel. The purpose
      of this article is to summarize how the examination is performed, and to specify
      appropriate indications and alternatives, performance characteristics, and
      anticipated future developments.

PMID- 18328437
TI  - What is the role of serologic testing in celiac disease? A prospective, biopsy
      confirmed study with economic analysis.
AB  - BACKGROUND & AIMS: The optimal serologic tests for the detection of celiac
      disease and follow-up assessment remains controversial. Our aim was to evaluate
      all current immunologic assays for diagnosing celiac disease using the gold
      standard of duodenal biopsy. We also assessed whether tissue transglutaminase
      (tTG) antibody is a quantitative marker for histologic severity. METHODS:
      Consecutive adult patients referred for gastroscopy without a previous known
      diagnosis of celiac disease were recruited (group 1). Concurrently, patients with
      a known diagnosis of celiac disease on a gluten-free diet for more than 1 year
      undergoing repeat duodenal biopsy were identified (group 2). All patients had
      duodenal biopsies and serologic analysis performed for immunoglobulin(Ig) A and
      antibodies to human immunoglobulin (Ig)A-tTG, IgA-gliadin, IgG-gliadin, and IgA
      endomysial antibody. RESULTS: Two thousand patients were recruited in the first
      group. Seventy-seven (3.9%) patients were diagnosed with new celiac disease. The
      sensitivity, specificity, positive predictive value, and negative predictive
      value for IgA tTG were 90.9%, 90.9%, 28.6%, and 99.6%. When adopting a 2-step
      approach using tTG first and then EMA the sensitivity, specificity, positive
      predictive value, and negative predictive value was 85.7%, 98.6%, 71.7%, and
      99.7%, respectively. The use of nondeamidated IgA/IgG gliadin antibodies
      conferred no additional diagnostic benefit when considering the detection of
      adult celiac disease. In the second group 48 patients with celiac disease on a
      gluten-free diet were identified. Sixteen of 48 of these patients had persisting
      villous atrophy, but 7 of 16 (44%) had a normal tTG level. CONCLUSIONS: IgA tTG
      alone is a sensitive marker for celiac disease. A normal tTG level does not
      predict recovery of villous atrophy in patients with celiac disease on a gluten
      free diet.

PMID- 18328438
TI  - Prognostic implications of lactate, bilirubin, and etiology in German patients
      with acute liver failure.
AB  - BACKGROUND & AIMS: Among the potentially helpful indicators of poor prognosis in
      acute liver failure (ALF) are etiology, encephalopathy grade, blood lactate, and
      King's College Criteria (KCC). The accuracy of these parameters in predicting
      transplantation or death shows significant variation in different countries.
      METHODS: We retrospectively analyzed 102 patients with ALF treated at our
      institution between 1996 and 2005. Baseline parameters, simplified acute
      physiology score III (SAPS-III), KCC, Model for End-Stage Liver Disease (MELD)
      score, and a novel score of bilirubin, lactate, and etiology (BiLE score) were
      compared between transplant-free survivors and patients who required liver
      transplantation or died, by using multivariate linear regression analysis and
      receiver operating characteristics (ROC). RESULTS: The most common causes of ALF
      were indeterminate liver failure (21%), acute hepatitis B (18%), acetaminophen
      ingestion (16%), and Budd-Chiari syndrome (9%). Transplantation-free survival was
      38%, 44% of patients underwent liver transplantation, and 18% died without
      transplantation. Eight-week survival was 77%. The BiLE score was the best
      predictor of death or need of transplantation, with 79% sensitivity and 84%
      specificity. ROC analysis revealed a better performance of BiLE score when
      compared with bilirubin, lactate, MELD score, and SAPS-III (area under the curve:
      0.87 +/- 0.04, 0.73 +/- 0.51, 0.73 +/- 0.52, 0.71 +/- 0.05, and 0.68 +/- 0.59,
      respectively). CONCLUSIONS: The simple, combined BiLE score emerged as the best
      predictor of poor outcome in our patient cohort and should be prospectively
      evaluated in other populations.

PMID- 18328439
TI  - Bleeding stomal varices: case series and systematic review of the literature.
AB  - BACKGROUND & AIMS: Bleeding stomal varices are a common problem in patients with
      surgical stomas and portal hypertension, and remain difficult to diagnose and
      manage. METHODS: We identified all patients at our institution with bleeding
      stomal varices from 1989 to 2004. We surveyed all patients undergoing ileal pouch
      anal anastomosis from 1997 to 2007 for bleeding anastomotic varices. Finally, we
      performed a systematic review of the literature focusing on diagnosis and
      treatment of bleeding stomal varices that included 74 English language studies of
      234 patients. RESULTS: We identified 8 patients with bleeding stomal varices.
      Recognition of stomal varices typically was delayed, particularly when failing to
      examine the ostomy without the appliance. Stomal variceal bleeding was confirmed
      by Doppler ultrasound or angiographic imaging. Simple local therapy usually
      stopped bleeding, albeit temporarily. Sclerotherapy was effective, but at the
      expense of unacceptable stomal damage. Decompressive therapy was required for
      secondary prophylaxis, including transjugular intravascular transhepatic shunts
      (2 patients), surgical portosystemic shunts (2 patients), and liver
      transplantation (1 patient). No patient with an ileal pouch-anal anastomosis
      developed anastomotic bleeding from varices. CONCLUSIONS: Primary prevention of
      bleeding stomal varices requires avoidance of creating enterocutaneous stomas in
      patients with portal hypertension. Careful inspection of the uncovered ostomy is
      essential for bleeding stomal varices diagnosis. Once identified, conservative
      measures will stop bleeding temporarily with definitive therapy required,
      including transjugular intravascular transhepatic shunts, surgical shunts, or
      liver transplantation.

PMID- 18328440
TI  - Dietary counseling versus dietary supplements for malnutrition in chronic
      pancreatitis: a randomized controlled trial.
AB  - BACKGROUND & AIMS: Up to 50% of patients with chronic pancreatitis (CP) are
      malnourished. There are limited data on the role of dietary intervention in
      improving the nutritional status of such patients. The aim was to compare the
      efficacy of medium chain triglyceride (MCT)-enriched commercial dietary
      supplements with dietary counseling for homemade food in the management of
      malnutrition in patients with CP. METHODS: In a randomized controlled trial,
      consecutive undernourished patients with CP (body mass index [BMI] <18.5 kg/m(2))
      at a tertiary care hospital were randomized to receive either dietary counseling
      for regular homemade food or commercial MCT-enriched dietary supplements for a
      period of 3 months to compensate for the dietary calorie deficit. All patients
      received standard management for CP including pancreatic enzyme supplements.
      Primary outcome measure was improvement in BMI. RESULTS: Sixty malnourished
      patients with CP were randomized to counseling group (n = 29; mean age, 32 +/- 10
      years; male, 83%) and supplementation group (n = 31; mean age, 28 +/- 10 years;
      male, 84%). BMI increased in both the counseling group and supplementation group
      (17.2 +/- 1.7 vs 18.1 +/- 1.8 kg/m(2), P = .001; 16.7 +/- 1.6 vs 18.2 +/- 1.6
      kg/m(2), P = .001). There were similar improvements in triceps skinfold
      thickness, dietary intake, fecal fat, and pain score during a period of 3 months
      in both groups. There was, however, no significant difference between the
      counseling and supplementation groups with regard to any of the outcome measures.
      CONCLUSIONS: Dietary counseling for a balanced homemade diet is as good as
      commercial food supplements in improving malnutrition in patients with CP.

PMID- 18328441
TI  - Rituximab therapy for refractory biliary strictures in immunoglobulin G4
      associated cholangitis.
AB  - BACKGROUND & AIMS: Biliary strictures occur in a third of patients with
      autoimmune pancreatitis and have been termed immunoglobulin G subclass 4 (IgG4)
      associated cholangitis (IAC). IAC often responds to steroid therapy. METHODS: A
      patient with autoimmune pancreatitis and (IAC) refractory to steroids and 6
      mercaptopurine was treated with rituximab, a monoclonal antibody directed against
      the CD20 antigen on B lymphocytes. RESULTS: The patient's biliary strictures
      improved after rituximab therapy, permitting removal of his biliary stents.
      Systemic manifestations of IgG4-associated disease also improved. CONCLUSIONS:
      Rituximab may be a treatment option for patients with refractory or recurrent
      autoimmune pancreatitis or IAC.

PMID- 18328442
TI  - Warifteine, a bisbenzylisoquinoline alkaloid, decreases immediate allergic and
      thermal hyperalgesic reactions in sensitized animals.
AB  - Warifteine is a bisbenzylisoquinoline alkaloid isolated from the Cissampelos
      sympodialis Eichl (Menispermaceae). This plant is used in the folk medicine for
      the treatment of airway respiratory diseases. A murine model of immediate
      allergic reaction was used to evaluate warifteine treatment in the IgE
      production, leukocyte activation, thermal hyperalgesia, mast cell degranulation
      and scratching behavior. BALB/c mice treated with warifteine (0.4-10 mg/Kg) 1 h
      before OVA sensitization reduced OVA induced paw edema as well as the OVA
      specific IgE serum titers as compared with non-treated and OVA-sensitized
      animals. Warifteine also reduced the mice death evoked by IgE-dependent
      anaphylactic shock reaction at 30 min after intravenous OVA challenge. To assess
      the effect of warifteine treatment on T cell proliferative response, spleen cells
      from warifteine treated or non-treated and OVA-sensitized animals were evaluated.
      Spleen cells from warifteine treated animals (2.0 mg/kg) did not proliferate
      following OVA stimulation as compared with spleen cell cultures from non-treated
      animals. This response may be related with the increase of NO production as
      observed in peritoneal macrophage cultures treated with warifteine. Thermal
      hyperalgesia evoked by IgE or histamine/5-hydroxytryptamine challenge was
      inhibited on rats at dose of 4.0 mg/kg. Warifteine treatment (0.6 or 6.0
      microg/ml) also decreased the IgEalphaDNP-BSA sensitized mast degranulation after
      DNP-BSA challenge measured by histamine release. In addition, compound 48/80
      induced scratching behavior was also sensitive to warifteine treatment. These
      results demonstrate for the first time that warifteine treatment reduced the
      allergy-associated responses.

PMID- 18328443
TI  - Evidence for an inhibitory immunomodulatory effect of selected antidepressants on
      rat splenocytes: possible relevance to depression and hyperactive-immune
      disorders.
AB  - Antidepressants have been found to possess antiproliferative effect. In the
      immune system depression may activate pro-inflammatory cytokines. Therefore, the
      aim of this study was to assess the immunomodulatory activity of antidepressants
      in naive rat. Rat splenocytes were activated with con A and treated with
      paroxetine, sertraline or clomipramine ex vivo. We found that the antidepressants
      inhibit cell viability and proliferation at IC50 of 5-8 microM of mitogen
      stimulated rat splenocytes. This inhibitory effect was accompanied by cell cycle
      arrest and increase in apoptotic events as assayed by FACS. Moreover,
      antidepressants decrease the secretion of the TH1 factor--TNFalpha. In addition,
      the antidepressants reduced the expression of the enzyme cyclooxygenase2 which is
      involved in inflammation. On the cellular level we show the up-regulation of MAPK
      death signaling pathway and suppression of the anti-apoptotic factor--Bcl-2.
      These findings reveal the immunomodulatory effect of the selected
      antidepressants. These data suggest a novel use of antidepressants or their
      derivatives.

PMID- 18328444
TI  - AIP1, a carbohydrate fraction from Artemisia iwayomogi, modulates the functional
      differentiation of bone marrow-derived dendritic cells.
AB  - Dendritic cells (DCs) are the most potent antigen-presenting cells (APC)
      particularly important in the initiation of primary T cell-mediated immune
      responses. Thus, inhibition of the differentiation and function of DC could lead
      to the suppression of immunological hyperresponsiveness. Artemisia iwayomogi, a
      member of the Compositae, is a perennial herb easily found in Korea and has been
      used as a traditional anti-inflammatory medicine. We investigated suppressive
      effects of carbohydrate fraction 1 from the water extracts of A. iwayomogi (AIP1)
      on the differentiation and function of bone marrow-derived dendritic cells. Bone
      marrow cells were cultured in the presence of granulocyte monocyte-colony
      stimulating factor (GM-CSF) and interleukin (IL)-4 for 6-7 days. Then, non
      adherent cells were harvested for subsequent analyses. Percentage(s) of CD11c+
      MHC II+ cell population(s) mostly composed of immature or mature DC and the
      allogeneic T cell stimulating ability of the cells were reduced by AIP1.
      Proteomic analyses along with RT-PCR revealed that expressions of several
      proteins including TNF receptor-associated factor (TRAF) 5-like protein, pyruvate
      kinase M2 (PKM2), and coactosin-like protein 1 (CLP1) were down-regulated upon
      AIP1 treatment.

PMID- 18328445
TI  - Resveratrol induces the suppression of tumor-derived CD4+CD25+ regulatory T
      cells.
AB  - CD4+CD25+ regulatory T cells (Treg cells) are negative regulator of the immune
      system and main obstacles to cancer immunotherapy in tumor-bearing hosts.
      Resveratrol is a natural product found in grapes with both immunomodulatory and
      anticancer effects, which can be controlled by Treg cells. Therefore, to
      determine whether resveratrol performs these actions via Treg cells, we
      investigated changes in Treg cell population and immunomodulatory cytokines in
      EG7 tumor-bearing C57BL/6 mice. In the present study, CD4+CD25+ cell population
      among CD4+ cells was inhibited ex vivo by resveratrol treatment in a dose
      dependent manner. FoxP3+ expressing cells among CD4+CD25+ population were
      significantly reduced after resveratrol treatment ex vivo in intracellular FACS
      analysis. Single intraperitoneal administration of 4 mg/kg resveratrol suppressed
      the CD4+CD25+ cell population among CD4+ cells and downregulated secretion of TGF
      beta, an immunosuppressive cytokine, measured from the spleens of tumor-bearing
      mice. Furthermore, resveratrol enhanced IFN-gamma expression in CD8+ T cells both
      ex vivo and in vivo,leading to immune stimulation. Taken together, these results
      suggest that resveratrol has a suppressive role on CD4+CD25+ cell population and
      makes peritumoral microenvironment unfavorable to tumor in tumor-bearing mice.
      Thus, resveratrol can be considered as possible adjuvant material for vaccination
      based cancer therapy.

PMID- 18328446
TI  - A pinusolide derivative, 15-methoxypinusolidic acid from Biota orientalis
      inhibits inducible nitric oxide synthase in microglial cells: implication for a
      potential anti-inflammatory effect.
AB  - The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota
      orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in
      microglial BV2 cells was investigated. 15-MPA significantly reduced the
      expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, and
      the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15
      MPA significantly suppressed the expressions of tumor necrosis factor (TNF)
      alpha, interleukin (IL)-6, and cyclooxygenase (COX)-2. However, 15-MPA did not
      affect LPS-induced degradation of inhibitor kappaB-alpha (IkappaB-alpha) and
      translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus. LPS
      activated p38 MAPK, extracellular signal-regulated kinase (ERK)-1/2, and stress
      activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were not affected by
      15-MPA. Taken together, this study demonstrates that 15-MPA inhibits LPS-induced
      iNOS expression and NO production, independent on MAPK and NF-kappaB, suggesting
      a potential anti-inflammatory effect of the compound on microglial cells.

PMID- 18328447
TI  - Contribution of dectin-1 and granulocyte macrophage-colony stimulating factor (GM
      CSF) to immunomodulating actions of beta-glucan.
AB  - beta-Glucans are major cell wall structural components in fungi. As they are not
      found in animals, these carbohydrates are considered to be classic pathogen
      associated molecular patterns (PAMPs), and are recognized by the innate immune
      system. Although their immunomodulating activities have been shown to be
      associated with the recognition of some fungi, and with their medicinal
      properties in the field of cancer immunotherapy, it is still unclear how beta
      glucans mediate their effects. Recent studies have started to shed some light on
      their cellular receptors, such as dectin-1, and their molecular mechanisms of
      action. We have extensively investigated the response of leukocytes to beta
      glucan, focusing on cytokine induction by SCG, which is a major 6-branched 1,3
      beta-d-glucan in Sparassis crispa Fr. There is a strain difference in the
      reactivity of mice to SCG, and DBA/1 and DBA/2 mice are highly sensitive strains.
      In the process of research on cytokine induction by SCG in DBA/2 mice, we found
      that GM-CSF plays a key biological role in this activity. Cytokine induction by
      SCG was completely abolished in dendritic cells from dectin-1 knockout mice. On
      the other hand, controlling the level of endogenous GM-CSF production and/or
      dectin-1 expression could regulate the reactivity to beta-glucan. These results
      indicate that the key factors in the responsiveness to beta-glucan are GM-CSF
      production and dectin-1 expression. In this review, we describe how the key
      molecules related to the expression of the immunomodulating activities of beta
      glucan were identified, and how the response to beta-glucan is controlled.

PMID- 18328448
TI  - Differential anti-inflammatory pathway by xanthohumol in IFN-gamma and LPS
      activated macrophages.
AB  - Macrophages are the main cells responsible for the innate immunity, and their
      activation by lipopolysaccharide (LPS) from Gram-negative bacteria or interferon
      (IFN)-gamma from host immune cells is important for controlling infections.
      However, the overwhelming activation of macrophages can cause a severe
      inflammatory state. This study investigated the inhibitory mechanism of
      xanthohumol (XN) against the inflammatory effectors (IL-1beta, TNF-alpha, and
      iNOS) in activated RAW264.7 macrophages by using different stimuli such as LPS,
      IFN-gamma, or LPS plus IFN-gamma. XN is a major prenylated chalcone found in
      hops, which is used to add bitterness and flavor to beer. XN reduced the
      expression of the LPS receptor components such as TLR4 and MD2 resulting in the
      suppression of NF-kappaB activation in LPS-activated RAW264.7 cells. In the IFN
      gamma stimulated RAW264.7 cells, the binding activity of STAT-1alpha and IRF-1
      was inhibited by XN. This suggests that differential signaling pathways are used
      by XN for the inhibition of excess inflammatory mediators depending on the
      stimuli in macrophages.

PMID- 18328449
TI  - Lactic acid bacteria inhibit proinflammatory cytokine expression and bacterial
      glycosaminoglycan degradation activity in dextran sulfate sodium-induced colitic
      mice.
AB  - To evaluate the effect of lactic acid bacteria (LAB) in inflammatory bowel
      diseases (IBD), inhibitory effect of several LAB isolated from intestinal
      microflora and commercial probiotics against NO production of lipopolysaccharide
      (LPS)-stimulated RAW264.7 cells was measured and anti-inflammatory effect of NO
      production-inhibitory LAB, Lactobacillus plantarum HY115 and L. brevis HY7401, in
      dextran sulfate sodium (DSS)-induced experimental colitic mice was investigated.
      The oral administration of the LAB to mice inhibited colon shortening and
      myeloperoxidase productivity in DSS-induced colitic mice. These LABs repressed
      the mRNA expressions of IL-1beta, TNF-alpha and IFN-gamma, as well as the protein
      expressions of IL-1beta and IL-6 proteins in the colon. The activation of the
      transcription factor, NF-kB, induced by DSS, was also inhibited by LAB. The
      administration of LAB reduced the degradation activities of chondroitin sulfate
      and hyaluronic acid of intestinal bacteria, induced by DSS, of which could induce
      the cytotoxic metabolites against intestinal cells. These findings suggest that
      NO-inhibitory LAB against LPS-stimulated RAW264.7 cells may improve colitis by
      the regulation of the inflammatory cytokine expression via the activation of
      transcription factor NF-kB as well as GAGs-degrading intestinal microflora.

PMID- 18328450
TI  - Stimulatory effect of a pectic polysaccharide from a medicinal herb, the roots of
      Bupleurum falcatum L., on G-CSF secretion from intestinal epithelial cells.
AB  - The inner surface of the intestinal tract possesses a large area of mucosal
      membranes, and the intestinal epithelial cells exist at the interface between an
      antigen-rich lumen and a lymphocyte-rich lamina propria. The crosstalk that
      occurs between these compartments serves to maintain intestinal homeostasis, and
      the cytokine network plays an important role in the crosstalk. In this study, the
      effect of a pectic polysaccharide, bupleuran 2IIc from Bupleurum falcatum L., on
      cytokine secretion of intestinal epithelial cells was investigated in vitro. When
      murine normal colonic epithelial cell line MCE301 cells were stimulated with
      bupleuran 2IIc, the contents of granulocyte colony-stimulating factor (G-CSF) in
      the conditioned medium were significantly increased in dose- and time-dependent
      manners. The enhanced G-CSF gene transcription in MCE301 cells by the stimulation
      of bupleuran 2IIc was observed by RT-PCR. The enhanced G-CSF secretion by
      bupleuran 2IIc was also observed in C3H/HeJ mice derived primary cultured colonic
      epithelial cells. Bupleuran 2IIc was digested with endo-(1-->4)-alpha-D
      polygalacturonase, and the resulting bupleuran 2IIc/PG-1 ("ramified" region)
      showed potent G-CSF secretion enhancing activity. The activity of bupleuran
      2IIc/PG-1 disappeared after the removal of arabinosyl residues from bupleuran
      2IIc/PG-1 by endo-(1-->5)-alpha-L-arabinanase digestion. These results suggest
      that the "ramified" region (bupleuran 2IIc/PG-1) is the active site for the G-CSF
      secretion enhancing activity of bupleuran 2IIc, and the arabinan moiety of
      bupleuran 2IIc/PG-1 plays an important role in expression of the activity.

PMID- 18328451
TI  - Treatment with cystamine reduces apoptosis in liver from NZB/W F1 mice.
AB  - Increased population with hepatic diseases and apoptosis were found in patients
      with SLE and implicated in the pathogenesis of SLE. Since cystamine has been
      demonstrated to be beneficial to NZB/W F1 mice in our previous report, this study
      intends to investigate the effects of cystamine in liver from NZB/W F1 mice.
      Decreased apoptosis was detected in liver from NZB/W F1 mice given cystamine as
      compared to those given PBS by TUNEL and caspase-3 activity assay. Fas-dependent
      apoptotic proteins including Fas, cleaved caspase-8 and tBid were reduced in
      liver from NZB/W F1 mice given cystamine as compared to those given PBS.
      Additionally, the mitochondria-dependent apoptotic proteins including cytochrome
      c and Apaf-1 were reduced in liver from NZB/W F1 mice given cystamine as compared
      to those given PBS. Moreover, increased BCL-2 protein was observed in liver from
      both mice. Notably, increased NF-kappaB protein was detected in liver from NZB/W
      F1 mice given cystamine as compared to those given PBS. These experimental
      results suggest the effect of cystamine in reducing apoptosis in liver from NZB/W
      F1 mice through Fas-dependent and mitochondrial-dependent pathways. The
      phosphorylation of NF-kappaB (p65) could be a possible mechanism involving anti
      apoptotic effects of cystamine in liver from NZB/W F1 mice.

PMID- 18328452
TI  - The natural prenylated flavone artelastin is an inhibitor of ROS and NO
      production.
AB  - Artelastin, a prenylated flavone previously isolated from Artocarpus elasticus,
      was evaluated for its effect on the production of reactive oxygen species (ROS)
      by human polymorphonuclear neutrophils (PMNs) and nitric oxide (NO) by J774
      murine macrophage cell line. Artelastin showed to be an inhibitor of ROS
      production due to a strong O2- scavenging activity. No effect was observed on the
      activity of myeloperoxidase (MPO). Artelastin showed also to be an inhibitor of
      NO production without NO scavenging activity. This flavone seems to interfere
      with the expression of the inducible nitric oxide synthase (iNOS) immediately
      after LPS-IFNgamma-macrophage stimulation.

PMID- 18328453
TI  - Low-level laser therapy decreases levels of lung neutrophils anti-apoptotic
      factors by a NF-kappaB dependent mechanism.
AB  - BACKGROUND AND OBJECTIVE: Low-level laser therapy (LLLT) is a known modulator of
      inflammatory process. Herein we studied the effect of 660 nm diode laser on mRNA
      levels of neutrophils anti-apoptotic factors in lipopolysaccharide (LPS)-induced
      lung inflammation. STUDY DESIGN/METHODOLOGY: Mice were divided into 8 groups (n=7
      for each group) and irradiated with energy dosage of 7.5 J/cm(2). The Bcl-xL and
      A1 mRNA levels in neutrophils were evaluated by Real Time-PCR (RT-PCR). The
      animals were irradiated after exposure time of LPS. RESULTS: LLLT and an
      inhibitor of NF-kappaB nuclear translocation (BMS 205820) attenuated the mRNA
      levels of Bcl-xL and A1 mRNA in lung neutrophils obtained from mice subjected to
      LPS-induced inflammation. CONCLUSION: LLLT reduced the levels of anti-apoptotic
      factors in LPS inflamed mice lung neutrophils by an action mechanism in which the
      NF-kappaB seems to be involved.

PMID- 18328454
TI  - Phenotypic variability associated to genomic changes in the main vector of Chagas
      disease in the southern cone of South America.
AB  - This study shows for the first time, the relationship between chromosomic and
      meristic quantitative characters of Triatoma infestans, the main vector of Chagas
      disease in the southern cone of South America. The antennal phenotype of 225
      adults from five countries and three cytotypes, were analyzed using univariate
      and multivariate techniques. The study found a clear association between
      cytotypes and antennal phenotypes. The complexity of the antennal sensilla
      pattern was higher in the non-Andean cytotype, showing more chemoreceptors
      usually linked to sexual behaviour, host finding and flight. The phenetic
      differences were more notorious on females than on males. Changes in the sexual
      dimorphism were detected, being the differences most notorious in the non-Andean
      cytotype. Similitude of the geographic populations using the antennal phenotype
      coincides with environmental gradient of the area, showing a close association
      between the physical features of the living zones and quantitative traits of the
      vectors. The epidemiological implications of the phenetic differences observed in
      the study are discussed.

PMID- 18328455
TI  - Hydrodynamic permeability of membranes built up by particles covered by porous
      shells: cell models.
AB  - A review is presented on an application of a cell method for investigations of
      hydrodynamic permeability of porous/dispersed media and membranes. Based on the
      cell method, a hydrodynamic permeability is calculated of a porous layer/membrane
      built up by solid particles with a porous shell and non-porous impermeable
      interior. Four known boundary conditions on the outer cell boundary are
      considered and compared: Happel's, Kuvabara's, Kvashnin's and Cunningham's
      (usually referred to as Mehta-Morse's condition). For description of a flow
      inside the porous shell Brinkman's equations are used. A flow around an isolated
      spherical particle with a porous shell is considered and a number of limiting
      cases are shown. These are compared with the corresponding results obtained
      earlier.

PMID- 18328456
TI  - Comparative therapy evaluation of intravitreal bevacizumab and triamcinolone
      acetonide on persistent diffuse diabetic macular edema.
AB  - PURPOSE: To compare the effect of an intravitreal injection of bevacizumab, an
      anti-vascular endothelial growth factor (VEGF) antibody, with that of
      triamcinolone acetonide, a corticosteroid for reduction of diabetic macular edema
      (DME). DESIGN: Prospective, comparative interventional case series. METHODS:
      Twenty-eight eyes of 14 patients with bilateral DME participated in this study.
      In each patient, one eye received an intravitreal injection of 4 mg triamcinolone
      acetonide and the other eye received 1.25 mg bevacizumab. The clinical course of
      best-corrected visual acuity (VA) with a logarithm of the minimum angle of
      resolution chart and averaged foveal thickness using optical coherence tomography
      was monitored for up to 24 weeks after the injection. RESULTS: Before the
      injection, foveal thickness and VA were 522.3 +/- 91.3 microm and 0.64 +/- 0.28
      microm in the triamcinolone-injected eye, and 527.6 +/- 78.8 microm and 0.61 +/-
      0.18 microm in the bevacizumab-injected eye, respectively; there was no
      significant difference between the eyes. One week after the injection, both eyes
      showed significant regression of macular edema. The triamcinolone-injected eye
      (342.6 +/- 85.5 microm and 0.33 +/- 0.21 microm) showed significantly better
      results than the bevacizumab-injected eye (397.6 +/- 103.0 microm and 0.37 +/-
      0.17 microm). However, both eyes showed the recurrence of macular edema with
      time, even at 24 weeks. Triamcinolone (410.4 +/- 82.4 microm and 0.47 +/- 0.25
      microm) kept better results than bevacizumab (501.6 +/- 92.5 microm and 0.61 +/-
      0.17 microm). CONCLUSIONS: With the generally used concentration, intravitreal
      injection of triamcinolone acetonide showed better results in reducing DME and in
      the improvement of VA than that of bevacizumab, suggesting that the pathogenesis
      of DME is not only attributable to VEGF-dependency, but is also attributable to
      other mechanisms suppressed by corticosteroid.

PMID- 18328457
TI  - [Swallowing sound signal: description in normal and laryngectomized subjects].
AB  - OBJECTIVES: Recently, we described three sound components in the pharyngeal
      swallowing sound. The aim of the present study was to identify the origin of
      these components using modern techniques providing numeric, synchronized acoustic
      radiological data in a normal population and in a partial supracricoid
      laryngectomized population (SCL group) and a total laryngectomized (TL group)
      population in pre- and postoperative situations. PATIENTS AND METHODS: We
      enrolled 15 normal subjects (10 men and five women; mean age, 29.5+/-8 years), 11
      patients in the SCL group (11 men; mean age, 62; range, 45-75 years), and nine
      patients in the TL group (three women, six men; mean age, 56; range, 39-73). An X
      ray camera was connected to a video acquisition card to obtain acoustic
      radiological data (2 images/s). The microphone was attached to each subject's
      skin overlying the lateral border of the cricoid. The subjects were asked to
      swallow 10 ml of a barium suspension. We performed the acoustic-radiological
      analysis using Visualisation and Cool Edit Pro software. Each sound component was
      associated with a specific position of the bolus and the moving anatomic
      structure. Three sound components were identified: the laryngeal ascension sound
      (LAS), the upper sphincter opening sound (USOS), and the laryngeal release sound
      (LRS). We quantified the total duration of the pharyngeal sound and its
      components, as well as the duration of the interval. RESULTS: The average
      duration of the normal pharyngeal sound was 690+/-162 ms and was significantly
      decreased in the TL group (296+/-105 ms) and increased in the SCL group (701+/
      186 ms). The USOS was present in 100% of the recordings. A typical profile of the
      swallowing sound for each group was obtained. CONCLUSION: This study allowed us
      to determine the origin of the three main sound components of the pharyngeal
      swallowing sound with respect to movements in anatomic structures and the
      different positions of the bolus, and to describe the main variations induced by
      a partial and a total laryngectomy.

PMID- 18328458
TI  - [Sinonasal hemangiopericytomas].
AB  - OBJECTIVES: The aim of this study was to report on the clinical, radiological and
      histological characteristics of hemangiopericytomas, and to discuss our
      experience with their treatment. MATERIAL AND METHODS: The authors reexamined two
      recent cases of patients presenting with sinonasal hemangiopericytomas
      (semiology, CT and MRI results, treatment and follow-up). RESULTS AND DISCUSSION:
      There was substantial variability of hemangiopericytoma presentation depending on
      location. Hemangiopericytomas of the nose and paranasal sinuses are considered a
      distinct entity with a good prognosis. Treatment is based on endoscopic sinus
      surgery. The histological approach requires the use of immunohistochemistry.
      Recurrences vary in the literature depending on the initial resection quality.
      Metastases are rare.

PMID- 18328459
TI  - [General review of rhinolithiases].
AB  - OBJECTIVE: The aim of this study was to analyze the clinical presentation and
      characteristics of rhinolithiasis, a rare and forgotten entity. METHODS: Between
      1990 and 2007, 20 cases of rhinolithiasis presented for consultation. The
      clinical course noted chronic nasal discharge associated with nasal obstruction.
      The protocol was the same for all patients: history of disease, meticulous
      endonasal endoscopy and plain radiography (+/-CT scan). RESULTS: Rhinolithiasis
      was found in adults (55%), females, patients living in rural areas (66%) with
      unfavorable socioeconomic conditions. The diagnosis delay varied between six
      months and eight years. The examination showed the rhinolith in the form of a
      grey concretion, primarily unilateral and on the right-hand side in 60% of the
      patients. Only one bilateral case presented following destruction of the
      posterior nasal septum. The rhinolith measured between 5 and 50mm in diameter
      with only three associated foreign bodies (15%). The rhinolith was extracted
      through the natural pathways under local anesthesia in 60% of the cases.
      Complications were rare (epistaxis 10%) and favorable progression without
      recurrence was generally observed after a mean 16 months of follow-up (range, six
      months to 11 years). CONCLUSION: Chronic nasal discharge without a history of
      rhinologic disease requires an endonasal examination under good conditions after
      retraction. Rhinolithiasis is easily recognized, in particular on imaging
      studies. Treatment is simple and curative in the majority of cases.

PMID- 18328460
TI  - Iron chelator differentially activates macrophage inflammatory protein
      3alpha/CCL20 in immortalized and malignant human oral keratinocytes.
AB  - Macrophage inflammatory protein-3alpha (MIP-3alpha or CCL20) is an intriguing
      molecule in cancer immunotherapy, but MIP-3alpha expression and signalling are
      not well understood in oral cancer cells. We investigated CCL20 expression and
      signal transduction by treating immortalized human oral keratinocyte (IHOK) and
      oral cancer (HN4) cells with deferoxamine (DFO) and examined the mRNA expression
      of CCL20 using RT-PCR and ELISA. IHOK and HN4 cells treated with DFO showed
      increased mRNA and protein expression of CCL20, and the upregulation of DFO
      induced CCL20 expression was higher in IHOK cells than in HN4 cells. Selective
      inhibitors of p38 and ERK1/2 abolished DFO-induced CCL20 expression in both IHOK
      and HN12 cells, and p38 and ERK1/2 inhibitors prevented DFO-induced degradation
      of I-kappaB and NF-kappaB activation. Activation of c-fos and c-jun also occurred
      following DFO treatment in IHOK and HN4 cells. Collectively, these results
      suggest that DFO-induced MIP-3alpha, which is involved in the MAP kinase, c-fos,
      c-jun, and NF-kappaB pathways, may be an important mediator of the antitumour
      immune response in oral keratinocytes and warrants consideration as a target
      molecule for oral cancer treatment.

PMID- 18328461
TI  - Low perception of control as a cognitive factor of eating disorders. Its
      independent effects on measures of eating disorders and its interactive effects
      with perfectionism and self-esteem.
AB  - OBJECTIVE: There is a large body of research about perfectionism and low self
      esteem in eating disorders (ED). However, little is known about the influence in
      ED of a distorted cognition in the domain of control: the perception of low
      control. The present study examined the main and interactive effects of concern
      over mistakes (an important dimension of perfectionism), self-esteem, and
      perception of control on drive for thinness, bulimia, and body dissatisfaction.
      METHOD: Forty individuals with ED and 55 controls completed the Multidimensional
      Perfectionism Scale, the Anxiety Control Questionnaire, the Rosenberg self-esteem
      scale, and the three symptomatic scales of the Eating Disorder Inventory, which
      are drive for thinness, bulimia and body dissatisfaction. Multiple linear
      regression was used to test the hypothesis that perception of low control has a
      significant effect on the symptomatic scales of the EDI. RESULTS: The ED group
      had significantly lower perception of control and self-esteem and higher concern
      over mistakes, drive for thinness, bulimia, and body dissatisfaction than the
      control group. Analysis of interactive effects suggested that a combination of a
      low perception of control and a low self-esteem seems to moderate the effects of
      concern over mistakes on drive for thinness, bulimia, and body dissatisfaction.
      DISCUSSION: ED are associated with a tendency to worry about mistakes, a low
      sense of self-esteem, and a low perception of control over internal feelings and
      external events. Perception of control and self-esteem seems to moderate the
      predictive power of concern mistakes on symptoms of ED. The results suggest that
      a low perception of control is an important cognitive factor in ED.

PMID- 18328462
TI  - The influence of data-driven versus conceptually-driven processing on the
      development of PTSD-like symptoms.
AB  - Ehlers and Clark [(2000). A cognitive model of posttraumatic stress disorder.
      Behaviour Research and Therapy, 38, 319-345] propose that a predominance of data
      driven processing during the trauma predicts subsequent PTSD. We wondered
      whether, apart from data-driven encoding, sustained data-driven processing after
      the trauma is also crucial for the development of PTSD. Both hypotheses were
      tested in two analogue experiments. Experiment 1 demonstrated that relative to
      conceptually-driven processing (n=20), data-driven processing after the film
      (n=14), resulted in more intrusions. Experiment 2 demonstrated that relative to
      the neutral condition (n=24) and the data-driven encoding condition (n=24),
      conceptual encoding (n=25) reduced suppression of intrusions and a trend emerged
      for memory fragmentation. The difference between the two encoding styles was due
      to the beneficial effect of induced conceptual encoding and not to the
      detrimental effect of data-driven encoding. The data support the viability of the
      distinction between data-driven/conceptually-driven processing for the
      understanding of the development of PTSD.

PMID- 18328463
TI  - Anxiety sensitivity and posttraumatic stress among traumatic event-exposed youth.
AB  - Total and factor scores of the Childhood Anxiety Sensitivity Index (CASI) were
      examined in relation to posttraumatic stress symptom levels within a community
      based sample of 68 (43 females) traumatic event-exposed youth between the ages of
      10 and 17 years (M age=14.74 years). Findings were consistent with hypotheses;
      global anxiety sensitivity (AS) levels, as well as disease, unsteady, and mental
      incapacitation concerns, related positively to posttraumatic stress levels,
      whereas social concerns were unrelated to symptom levels. These results suggest
      that fears of the physical and mental consequences of anxiety are associated with
      relatively higher levels of posttraumatic stress subsequent to traumatic event
      exposure. Findings are discussed in terms of potential implications for the role
      of AS in developmentally sensitive etiological models of posttraumatic stress
      disorder (PTSD).

PMID- 18328464
TI  - Prognostic significance of two sub-categorization methods for the treatment of
      binge eating disorder: negative affect and overvaluation predict, but do not
      moderate, specific outcomes.
AB  - Given the absence of known predictors and moderators for binge eating disorder
      (BED) treatment outcome and recent findings regarding meaningful sub
      categorizations of BED patients, we tested the predictive validity of two
      subtyping methods. Seventy-five overweight patients with BED who participated in
      a randomized clinical trial of guided self-help treatments (cognitive-behavioral
      therapy (CBTgsh) and behavioral weight loss (BWLgsh)) were categorized in two
      ways. First, a cluster analytic approach yielded dietary-negative affect (29%)
      and pure dietary (71%) subtypes. Second, research conventions for categorizing
      patients based upon shape or weight self-evaluation yielded clinical
      overvaluation (51%) and subclinical overvaluation (49%) subtypes. At the end of
      treatment, participants subtyped as dietary-negative affect reported more
      frequent binge episodes compared to the pure dietary subtype, and those with
      clinical overvaluation reported greater eating disorder psychopathology compared
      to the subclinical overvaluation group. Neither method predicted binge remission,
      depressive symptoms, or weight loss. Neither sub-categorization moderated the
      effects of guided self-help CBT and BWL treatments on any BED outcomes,
      suggesting that these two specific treatments perform comparably across BED
      subtypes. In conclusion, dietary-negative affect subtyping and overvaluation
      subtyping each predicted, but did not moderate, specific and important dimensions
      of BED treatment outcome.

PMID- 18328465
TI  - Pre-stressor cognitive control is related to intrusive cognition of a stressful
      film.
AB  - It has been suggested that relatively weak cognitive control existing prior to a
      stressful event may be associated with intrusive memories of that stressor
      afterwards. We explored this in two analog studies employing unselected
      participants who saw an emotional film fragment and completed behavioral (i.e.,
      color-naming interference [CNI]) and self-report indices of intrusions. Prior to
      film presentation, several cognitive control tests were administered. Study 1
      showed that better updating/monitoring was linked to less CNI from negative film
      related words. However, better updating/monitoring was associated with more diary
      reports of intrusive memories. Study 2 showed that a better resistance to pro
      active interference (PI) predicted less self-reported film-related intrusive
      cognition after 24h. However, after this delay, both self-reported intrusions and
      CNI were not related to updating/monitoring. Taken together, the results suggest
      that a specific pre-existing cognitive control function (i.e., resistance to PI)
      may be involved in the regulation of post-stressor intrusive memory phenomena.

PMID- 18328466
TI  - Cell proliferation during early diencephalon development in Alligator.
AB  - Using immunocytochemical methodology, cell proliferation was investigated in
      Alligator during early diencephalon development. These results were compared with
      cell proliferation during early hindbrain formation in this same species using
      identical techniques. The pattern of cell proliferation in the diencephalon
      differed from that observed in the rhombencephalon. If cell proliferation is a
      factor influencing brain development, then the diencephalon of Alligator may be
      built differently from the hindbrain.

PMID- 18328467
TI  - Structural investigation of a polysaccharide (Fr. I) isolated from the aqueous
      extract of an edible mushroom, Volvariella diplasia.
AB  - A water-soluble polysaccharide, (Fr. I) isolated from the aqueous extract of an
      edible mushroom, Volvariella diplasia, is composed of D-glucose, D-mannose, and D
      galactose in a molar ratio 3:1:1. Compositional analysis, methylation analysis,
      periodate oxidation study, Smith degradation, and NMR studies (1H, 13C, DQF-COSY,
      TOCSY, NOESY, ROESY, HMQC, and HMBC) revealed the presence of the following
      repeating unit in the polysaccharide: [Formula: see text].

PMID- 18328468
TI  - Synthesis of lupane-type saponins bearing mannosyl and 3,6-branched trimannosyl
      residues and their evaluation as anticancer agents.
AB  - The saponins modified with mono- or trimannosyl residues can provide a convenient
      means of delivering drugs to certain human cells via interactions with mannose
      receptors. In the study reported therein, we developed a convenient approach for
      the synthesis of 3-O-mannoside and branched trimannoside derivatives of the
      saponin lupeol and of C-28 acyl esters of 3-O-acetyl-betulinic acid bearing the
      same mannosyl entities. Lupeol and 3-O-acetyl-betulinic acid were mannosylated
      with tetra-O-benzoyl- or tetra-O-acetyl-alpha-D-mannopyranosyl
      trichloroacetimidates. De-esterification followed by regioselective
      dimannosylation of the unprotected monosaccharide derivatives with 2equiv of
      tetra-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate selectively yielded O
      3,O-6-linked trimannosides. The cytotoxic activity of selected lupane-type
      saponins (derivatives of lupeol, betulinic acid, and betulin) toward normal human
      fibroblasts and various cancer cell lines was also compared.

PMID- 18328469
TI  - Prediction of non-genotoxic carcinogenesis in rats using changes in gene
      expression following acute dosing.
AB  - Non-genotoxic carcinogenicity of chemicals is currently routinely evaluated in 2
      year rodent bioassays. Therefore, the development of early biomarkers for non
      genotoxic carcinogenesis would result in substantial savings in time and expense.
      The current study investigates whether early changes in gene expression may be
      developed as markers for cancer. Animals were treated for 1 or 5 days with either
      non-genotoxic carcinogens (NGTCs) or non-carcinogens and gene expression was
      analyzed by quantitative PCR (qPCR). We tested two gene signatures previously
      reported to detect non-genotoxic carcinogens. Using one gene signature it was
      confirmed that 3/3 non-genotoxic carcinogens and 2/2 non-carcinogens are
      correctly identified with data from 1 or 5 days of dosing. In contrast an
      alternative signature correctly identified 0/3 and 2/3 non-genotoxic carcinogens
      at 1 and 5 days of treatment, respectively and 2/2 non-carcinogens at both time
      points. Additionally, we evaluated a novel panel of putative biomarker genes,
      from the literature, many of which have roles in cell growth and division,
      including myc, cdc2 and mcm6. These genes were significantly induced by non
      genotoxic carcinogens and not by non-carcinogens. Using the average fold
      induction across this panel, 2/3 non-genotoxic carcinogens were detected at both
      1 and 5 days. These data support the idea that acute changes in gene expression
      may provide biomarkers for non-genotoxic carcinogenesis but also highlight
      interesting differences in the sensitivities of distinct gene signatures.

PMID- 18328470
TI  - Categorical variables, interactions and generalized additive models. Applications
      in computer-aided diagnosis systems.
AB  - Recently, the generalized additive models (GAMs) have been presented as a novel
      statistical approach to distinguish lesion/non-lesion in computer-aided diagnosis
      (CAD) systems. In this paper, we present an extension of the GAM that allows for
      the introduction of factors and their interactions with continuous variables, for
      reducing false positives in a CAD system for detecting clustered
      microcalcifications in digital mammograms. The results obtained have shown an
      increase in the sensitivity from 83.12% to 85.71%, while the false positive rate
      was drastically reduced from 1.46 to 0.74 false detections per image.

PMID- 18328471
TI  - Development of a mobile pulse waveform analyzer for cardiovascular health
      monitoring.
AB  - Noninvasive pulse waveforms contain rich pathophysiological information of
      cardiovascular system. It is hereby a tradition of interest to implement risk
      stratification by pulse waveform monitoring and analysis. In contrast to
      conventional computer- or network-based solutions, we attempt to accomplish pulse
      waveform monitoring and analysis within a self-contained mobile platform. It
      adopts a compact biosensor for pulse waveform acquisition. The collected signals
      are then submitted to a core board for pulse waveform processing and analysis. In
      addition, the core board coordinates user interaction and network communication
      too. Such compact pulse waveform analyzer is of great help for cardiovascular
      health monitoring at home. A carefully designed evaluation has been undertaken
      within our research group. The results confirmed its prospect in home healthcare.

PMID- 18328472
TI  - The Fat-like cadherin CDH-4 controls axon fasciculation, cell migration and
      hypodermis and pharynx development in Caenorhabditis elegans.
AB  - Cadherins are one of the major families of adhesion molecules with diverse
      functions during embryonic development. Fat-like cadherins form an evolutionarily
      conserved subgroup characterized by an unusually large number of cadherin repeats
      in the extracellular domain. Here we describe the role of the Fat-like cadherin
      CDH-4 in Caenorhabditis elegans development. Cdh-4 mutants are characterized by
      hypodermal defects leading to incompletely penetrant embryonic or larval
      lethality with variable morphogenetic defects. Independently of the morphogenetic
      defects cdh-4 mutant animals also exhibit fasciculation defects in the ventral
      and dorsal cord, the major longitudinal axon tracts, as well as migration defects
      of the Q neuroblasts. In addition CDH-4 is essential for establishing and
      maintaining the attachment between the buccal cavity and the pharynx. Cdh-4 is
      expressed widely in most affected cells and tissues during embryogenesis
      suggesting that CDH-4 functions to ensure that proper cell contacts are made and
      maintained during development.

PMID- 18328473
TI  - Shape and function of the Bicoid morphogen gradient in dipteran species with
      different sized embryos.
AB  - The Bicoid morphogen evolved approximately 150 MYA from a Hox3 duplication and is
      only found in higher dipterans. A major difference between dipteran species,
      however, is the size of the embryo, which varies up to 5-fold. Although the
      expression of developmental factors scale with egg length, it remains unknown how
      this scaling is achieved. To test whether scaling is accounted for by the
      properties of Bicoid, we expressed eGFP fused to the coding region of bicoid from
      three dipteran species in transgenic Drosophila embryos using the Drosophila
      bicoid cis-regulatory and mRNA localization sequences. In such embryos, we find
      that Lucilia sericata and Calliphora vicina Bicoid produce gradients very similar
      to the endogenous Drosophila gradient and much shorter than what they would have
      produced in their own respective species. The common shape of the Drosophila,
      Lucilia and Calliphora Bicoid gradients appears to be a conserved feature of the
      Bicoid protein. Surprisingly, despite their similar distributions, we find that
      Bicoid from Lucilia and Calliphora do not rescue Drosophila bicoid mutants,
      suggesting that that Bicoid proteins have evolved species-specific functional
      amino acid differences. We also found that maternal expression and anteriorly
      localization of proteins other than Bcd does not necessarily give rise to a
      gradient; eGFP produced a uniform protein distribution. However, a shallow
      gradient was observed using eGFP-NLS, suggesting nuclear localization may be
      necessary but not sufficient for gradient formation.

PMID- 18328474
TI  - Beta1 integrin expression by podocytes is required to maintain glomerular
      structural integrity.
AB  - Integrins are transmembrane heteromeric receptors that mediate interactions
      between cells and extracellular matrix (ECM). beta1, the most abundantly
      expressed integrin subunit, binds at least 12 alpha subunits. beta1 containing
      integrins are highly expressed in the glomerulus of the kidney; however their
      role in glomerular morphogenesis and maintenance of glomerular filtration barrier
      integrity is poorly understood. To study these questions we selectively deleted
      beta1 integrin in the podocyte by crossing beta1(flox/flox) mice with podocyte
      specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular
      capillary formation. We demonstrate that podocyte abnormalities are visualized
      during glomerulogenesis of the pod-Cre;beta1(flox/flox) mice and proteinuria is
      present at birth, despite a grossly normal glomerular basement membrane.
      Following the advent of glomerular filtration there is progressive podocyte loss
      and the mice develop capillary loop and mesangium degeneration with little
      evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end
      stage renal failure characterized by both tubulointerstitial and glomerular
      pathology. Thus, expression of beta1 containing integrins by the podocyte is
      critical for maintaining the structural integrity of the glomerulus.

PMID- 18328475
TI  - Identification of downstream genetic pathways of Tbx1 in the second heart field.
AB  - Tbx1, a T-box transcription factor, and an important gene for velo-cardio-facial
      syndrome/DiGeorge syndrome (VCFS/DGS) in humans, causes outflow tract (OFT) heart
      defects when inactivated in the mouse. Tbx1 is expressed in the second heart
      field (SHF) and is required in this tissue for OFT development. To identify Tbx1
      regulated genetic pathways in the SHF, we performed gene expression profiling of
      the caudal pharyngeal region in Tbx1(-/-) and wild type embryos. Isl1, a key
      marker for the SHF, as well as Hod and Nkx2-6, were downregulated in Tbx1(-/-)
      mutants, while genes required for cardiac morphogenesis, such as Raldh2, Gata4,
      and Tbx5, as well as a subset of muscle contractile genes, signifying myocardial
      differentiation, were ectopically expressed. Pan-mesodermal ablation of Tbx1
      resulted in similar gene expression changes, suggesting cell-autonomous roles of
      Tbx1 in regulating these genes. Opposite expression changes concomitant with SHF
      derived cardiac defects occurred in TBX1 gain-of-function mutants, indicating
      that appropriate levels of Tbx1 are required for heart development. When taken
      together, our studies show that Tbx1 acts upstream in a genetic network that
      positively regulates SHF cell proliferation and negatively regulates
      differentiation, cell-autonomously in the caudal pharyngeal region.

PMID- 18328476
TI  - Neural crest invasion is a spatially-ordered progression into the head with
      higher cell proliferation at the migratory front as revealed by the
      photoactivatable protein, KikGR.
AB  - Neural crest cell (NCC) invasion is a complex sculpting of individual cells into
      organized migratory streams that lead to organ development along the vertebrate
      axis. Key to our understanding of how molecular mechanisms modulate the NCC
      migratory pattern is information about cell behaviors, yet it has been
      challenging to selectively mark and analyze migratory NCCs in a living embryo.
      Here, we apply an innovative in vivo strategy to investigate chick NCC behaviors
      within the rhombomere 4 (r4) migratory stream by combining photoactivation of
      KikGR and confocal time-lapse analysis of H2B-mRFP1 transfected NCCs. We find
      that the spatial order of r4 NCC emergence translates into a distal-to-proximal
      invasion of the 2nd branchial arch. Lead and trailing NCCs display similar
      average cell speeds and directionalities. Surprisingly, we find that lead NCCs
      proliferate along the migratory route and grow to outnumber trailing NCCs by
      nearly 3 to 1. A simple, cell-based computational model reproduces the r4 NCC
      migratory pattern and predicts the invasion order can be disrupted by slower,
      less directional lead cells or by environmental noise. Our results suggest a
      model in which NCC behaviors maintain a spatially-ordered invasion of the
      branchial arches with differences in cell proliferation between the migratory
      front and trailing NCCs.

PMID- 18328477
TI  - Sustained morphine treatment augments basal CGRP release from cultured primary
      sensory neurons in a Raf-1 dependent manner.
AB  - Recent studies suggest that sustained morphine-mediated paradoxical pain may play
      an important role in the development of analgesic tolerance. The intracellular
      signal transduction pathways involved in sustained opioid mediated augmentation
      of spinal pain neurotransmitter (such as calcitonin gene-related peptide (CGRP))
      release are not fully clarified. Cyclic AMP (cAMP)-dependent protein kinase (PKA)
      plays an important role in the modulation of presynaptic neurotransmitter
      release. Moreover, we have shown earlier that sustained opioid agonist treatment
      leads to a Raf-1-dependent sensitization of adenylyl cyclase(s) (AC
      superactivation), augmenting forskolin-stimulated cAMP formation upon opioid
      withdrawal (cAMP overshoot). Therefore, in the present study we examined the role
      of Raf-1 in sustained morphine-mediated regulation of cAMP formation and basal
      CGRP release in vitro, in cultured neonatal rat dorsal root ganglion (DRG)
      neurons. We found that sustained morphine treatment significantly augments
      intracellular cAMP production as well as basal CGRP release from cultured
      neonatal rat DRG neurons. The selective PKA inhibitor, H-89, attenuates the
      sustained morphine-mediated augmentation of basal CGRP release, indicating that
      the cAMP/PKA pathway plays an important role in regulation of CGRP release from
      sensory neurons. Since our present data also demonstrated that selective Raf-1
      inhibitor, GW 5074, attenuated both the cAMP overshoot and the augmentation of
      CGRP release mediated by sustained morphine in neonatal rat DRG neurons, we
      suggest that Raf-1-mediated sensitization of the intracellular cAMP formation may
      play an important role in sustained morphine-mediated augmentation of spinal pain
      neurotransmitter release.

PMID- 18328478
TI  - p38MAPK inhibition attenuates LPS-induced acute lung injury involvement of NF
      kappaB pathway.
AB  - The pathogenesis of acute lung injury/acute respiratory distress syndrome (ARDS)
      is complex and involves multiple signal transduction processes. It is believed
      that p38MAPK (mitogen-activated protein kinase) is one of the most kinases in
      inflammatory signaling. At present study, we demonstrated the role of p38MAPK in
      lipopolysaccharide (LPS)-induced acute lung injury with pharmacologic p38MAPK
      inhibition by SB203580. SB203580, p38MAPK specific inhibitor, was injected (10
      mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). The hematoxylin
      eosin staining of lung tissues showed that p38MAPK inhibition significantly
      attenuated the pulmonary inflammatory responses induced by LPS. Moreover,
      SB203580 can also inhibit the inflammatory cytokine release, and reduce the
      mortality rate of LPS-induced acute lung injury. Further, western blot analysis
      that showed SB203580 administration can inhibit the activation of NF-kappaB,
      which was associated with the inhibition of IkappaBalpha degradation in
      cytoplasm. These data suggest that p38MAPK signaling may be involved in the
      activation of NF-kappaB, and activation of p38MAPK signaling may be one of the
      mechanisms of acute lung injury.

PMID- 18328479
TI  - Attenuation of MPTP neurotoxicity by rolipram, a specific inhibitor of
      phosphodiesterase IV.
AB  - Rolipram, a specific inhibitor of the phosphodiesterase IV (PDE IV), has recently
      been shown to exert neuroprotective effects in an Alzheimer transgenic mouse
      model and in hypoxic-ischemic damage in the rat brain. It activates the cAMP
      dependent protein kinase (PKA)/cAMP regulatory element-binding protein (CREB)
      signaling pathway and it inhibits inflammation. We tested the neuroprotective
      effects of the specific PDE IV inhibitor rolipram in C57BL/6 mice treated with 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We found that rolipram
      administered at 1.25 mg/kg or 2.5 mg/kg doses significantly attenuated MPTP
      induced dopamine depletion in the striatum, and reduced the loss of tyrosine
      hydroxylase-positive neurons in the substantia nigra. There was a bell-shaped
      dose effect with greater efficacy at the 1.25 mg/kg dose than 2.5 mg/kg and a
      higher dose of rolipram, 5 mg/kg, had no protective effect and even increased the
      mortality of animals when co-administered with MPTP. Rolipram did not interact
      with MPTP in its absorption into the brain and in its metabolism to 1-methyl-4
      phenylpyridinium (MPP(+)). Our data show a neuroprotective effect of the PDE IV
      specific inhibitor rolipram against dopaminergic neuron degeneration, suggesting
      that PDE IV inhibitors might be a potential treatment for Parkinson's disease.

PMID- 18328481
TI  - Contraception in hereditary angioedema.
AB  - OBJECTIVE: To report a case of successful use of a transdermal contraceptive in a
      patient with hereditary angioedema. DESIGN: Case report. SETTING: University
      medical center. PATIENT(S): A patient who had used oral contraceptives contracted
      SC and submucosal tumefaction every 1 or 2 months. She was diagnosed with type I
      hereditary angioedema. It was determined that she was complement C4 deficient and
      C1-inhibitor quantitative deficient but functional C1-inhibitor normal. After she
      was diagnosed, the use of oral contraceptives was contraindicated.
      INTERVENTION(S): Oral contraceptives were suspended, and a hormonal transdermal
      contraceptive was started. MAIN OUTCOME MEASURE(S): The absence of symptoms after
      26 months using a transdermal contraceptive. RESULT(S): After 26 months of using
      this treatment, the patient has not experienced any symptoms of the hereditary
      angioedema. CONCLUSION(S): The use of hormonal contraceptives transdermally can
      be an alternative in patients with hereditary angioedema.

PMID- 18328480
TI  - Evidence for a Mullerian-inhibiting substance autocrine/paracrine system in adult
      human endometrium.
AB  - OBJECTIVE: To determine if adult human endometrium possesses an intact mullerian
      inhibiting substance (MIS) signal transduction system and, if so, whether MIS can
      modulate endometrial cell viability. DESIGN: Adult human endometrial tissue was
      subjected to reverse transcription polymerase chain reaction (RT-PCR) analysis
      and immunohistochemistry. In addition, cultured human endometrial stromal cells
      were treated with recombinant MIS or transiently transfected with MIS and/or MIS
      type II receptor (MISRII) expression plasmids to assess for effects upon
      endometrial cell viability and apoptosis. The MIS in conditioned media was
      quantified by specific ELISA. SETTING: Academically affiliated medical center.
      PATIENT(S): Reproductive-age women undergoing routine infertility evaluation.
      INTERVENTION(S): Endometrial sampling. MAIN OUTCOME MEASURE(S): Assessment of MIS
      gene transcription and protein translation in human endometrial tissue in vivo
      and in vitro. RESULT(S): 1) The RT-PCR revealed that adult human endometrium
      expresses the genes for MIS, MISRII, ALK3, and Smads 1 and 9. 2)
      Immunohistochemistry reveals that MIS and MISRII protein are expressed in human
      endometrium. 3) Immunocytochemistry of cultured human endometrial cells reveals
      that MIS and MISRII protein are primarily restricted to mitosing cells. 4) ELISA
      reveals that MIS is secreted by human endometrial cells in vitro and that this
      process is increased by sex steroids. 5) Increasing local MIS concentration in
      cultured human endometrial stromal cells either by exogenous administration or
      transient transfection significantly decreases cell viability and increases
      apoptosis. CONCLUSION(S): Adult human endometrium possesses a functional MIS
      signal transduction system which negatively regulates cellular viability.

PMID- 18328482
TI  - Menstrual cycle synchronization, ovarian stimulation, and in vitro fertilization
      in olive baboons (Papio anubis): a prospective randomized study.
AB  - OBJECTIVE: To synchronize the baboon menstrual cycle and to compare different
      methods of ovarian stimulation for IVF in baboons. DESIGN: Prospective randomized
      study. SETTING: Institute of Primate Research, Nairobi, Kenya. ANIMAL(S): Ten
      female baboons were treated with an oral contraceptive (33 +/- 8 days) and
      randomized for ovarian stimulation in two cycles. INTERVENTION(S): In cycle 1
      (C1), baboons were stimulated as follows: clomiphene citrate (CC) for 5 days
      followed by antagonist (group CC-1, n = 3); recombinant gonadotropins (rGn: rFSH
      and rLH) with antagonist (group antagon-1, n = 3); and long GnRH agonist protocol
      (group LP-1, n = 4). After 1- month rest, in cycle 2 (C2), the baboons were
      stimulated as follows: CC for 8 days without antagonist (group CC-2, n = 2);
      short GnRH agonist protocol (group SP-2, n = 4); long GnRH agonist protocol
      (group LP-2, n = 4). Oocyte aspiration was performed 34-36 hours after injecting
      5000 IU recombinant hCG; the oocytes were then fertilized. MAIN OUTCOME
      MEASURE(S): Oocytes retrieved and fertilization rate. RESULT(S): Withdrawal
      bleeding occurred 4 +/- 1 days after the cessation of the contraceptive. Ovarian
      stimulation using the different protocols resulted in the following mean numbers
      of retrieved oocytes: LP-1, n = 19; LP-2, n = 19; CC-1, n = 4; CC-2, n = 4;
      antagon-1, n = 9; and SP-2, n = 14. Fertilization by intracytoplasmic sperm
      injection varied (23%-54%). CONCLUSION(S): The baboon menstrual cycle can be
      synchronized using an oral contraceptive. A long GnRH agonist protocol for
      ovarian stimulation may be suitable for ovarian stimulation in baboons.

PMID- 18328483
TI  - Pathophysiologic features of "thin" endometrium.
AB  - OBJECTIVE: To characterize pathophysiologic features of a "thin" endometrium.
      DESIGN: A prospective observational study. SETTING: University Hospital and City
      General Hospital. PATIENT(S): Patients with normal-thickness endometrium (Normal
      Em group: endometrial thickness >or=8 mm; n = 57) and thin endometrium (Thin-Em
      group: endometrial thickness <8 mm; n = 17). MAIN OUTCOME MEASURE(S): Blood flow
      impedance of the uterine radial artery (RA) was assessed as resistance index (RI)
      by transvaginal color-pulsed Doppler ultrasonography. The area of glandular
      epithelium, the number of blood vessels, and vascular endothelial growth factor
      (VEGF) expression were examined in the midluteal-phase endometrium. RESULT(S):
      The RA-RI in the Thin-Em group was significantly higher than in the Normal-Em
      group throughout the menstrual cycle. Endometrial thickness was significantly
      correlated with RA-RI. Growth of glandular epithelium, the number of blood
      vessels, and VEGF expression were significantly lower in the Thin-Em group than
      in the Normal-Em group. CONCLUSION(S): A "thin" endometrium was characterized by
      high blood flow impedance of RA, poor epithelial growth, decreased VEGF
      expression, and poor vascular development.

PMID- 18328484
TI  - Hysteroscopic unification of a complete obstructing uterine septum: case report
      and review of the literature.
AB  - OBJECTIVE: To report a case of complete obstructing uterine septum repaired in a
      minimally invasive manner by operative hysteroscopy under laparoscopic guidance.
      A complete obstructing uterine septum is a rare congenital abnormality. To date,
      management of such abnormalities has traditionally been by metroplasty. DESIGN:
      Case report and review of the literature. SETTING: Pediatric and adolescent
      gynecology service at a tertiary care hospital. PATIENT(S): A 16-year-old
      nulligravid presented with severe, persistent dysmenorrhea and a history of
      significant endometriosis. Imaging initially suggested a functional,
      noncommunicating uterine horn, but magnetic resonance imaging review confirmed a
      complete obstructing septate uterus. INTERVENTION(S): The patient was managed by
      menstrual suppression until the time of surgery. The septum was resected by
      operative hysteroscopy under laparoscopic guidance. The procedure was without
      complication. MAIN OUTCOME MEASURE(S): The patient recovered well and resumed
      spontaneous menses without dysmenorrhea. RESULT(S): A second-look hysteroscopy 4
      months later confirmed patency of the previously obstructed side and allowed the
      opportunity to complete the resection of the septum. CONCLUSION(S): Operative
      hysteroscopy is an effective and safe minimally invasive technique to manage the
      rare complete obstructing uterine septum. Hysteroscopy is less invasive than
      traditional metroplasty and is associated with easier recovery. Additionally,
      there is no uterine scar and thus less implication for future fertility. Further
      series of such procedures are required to offer greater experience and proof of
      safety of this approach.

PMID- 18328485
TI  - Spatial scaling laws do not structure strongyloid nematode communities in
      macropodid hosts.
AB  - The characteristics of species within a community can influence the number of
      species that can coexist within that community. In particular, body size can
      constrain how many individuals can 'fit' into a community, and overlap in
      resource use between species depends on differences in their body sizes. Here,
      using data from 18 communities of strongyloid nematodes living in the stomachs of
      macropodid marsupials, we test key predictions derived from spatial scaling laws
      regarding the minimum similarity in body size between coexisting species believed
      to control how many species can coexist in a community. These communities are
      ideal systems for such a test: they consist of huge numbers of individuals from
      numerous species, all belonging to the same family (Chabertiidae) and living in
      the same host organ. Within these communities, we found that mean abundance
      correlated negatively with body size across all nematode species, whether body
      size was measured as length or volume. However, we found no support for the
      predictions of spatial scaling laws. First, the size ratios of pairs of adjacent
      sized species did not decrease as a function of the size of the largest species
      in a pair. The few significant relationships observed were all positive,
      suggesting that the relative difference in size between adjacent species in the
      size hierarchy may in fact increase toward the upper end of the size spectrum.
      Second, the frequency distributions of body sizes were predominantly right-skewed
      amongst the communities investigated: within the size spectrum observed in a
      nematode community, small-bodied species greatly outnumber large-bodied ones, in
      sharp contrast to the predictions of spatial scaling laws. Nematode body size may
      thus determine the abundance achieved by a species but not how many species can
      coexist; the limiting similarity between coexisting species must depend on other
      biological traits.

PMID- 18328486
TI  - Serological responses in porcine cysticercosis: a link with the parasitological
      outcome of infection.
AB  - An oral infection model with Taenia solium whole proglottids was used to study
      host-parasite relationships and the mechanisms underlying resistance to infection
      in pigs. In addition, an attempt was made to link the parasitological findings to
      serological data. Groups of six piglets aged 1, 3 and 5 months were infected and
      slaughtered 3 months p.i. Circulating antibody and antigen levels were monitored
      weekly. At autopsy total cyst counts were performed. Although the detailed
      carcass dissection at necropsy revealed a high variation in the number of cysts,
      the trend was that the number of viable cysts decreased with the age at which the
      animals were infected. The kinetics of the antigen levels throughout the course
      of the infection differed markedly between the three age groups of the
      experimental infection model. In the younger animals, a fast increase in titres
      of circulating antigen was observed in most animals, reaching a plateau as early
      as 2 weeks p.i. Besides its faster increase, antigen levels in pigs infected at
      younger ages also reached higher levels than in older animals and were associated
      with weaker antibody responses. Results also demonstrated that a relationship
      exists between the number of cysts and the titre of circulating antigen. This is
      promising in view of the development of an assay to quantify the progress of an
      active T. solium infection and would be a useful tool in epidemiological studies
      to assess the infection burden and the risk of transmission of the disease. The
      use of specific antibody-detection assays combined with circulating antigen
      detection could improve our understanding of this relationship.

PMID- 18328487
TI  - A computational study of knitted Nitinol meshes for their prospective use as
      external vein reinforcement.
AB  - External reinforcement has been suggested for autologous vein grafts to address
      the mismatch of mechanical properties and fluid dynamics of graft and host
      vessel, a main factor for graft failure. A finite-element tool was developed to
      investigate the mechanical behaviour, in particular radial compliance, of knitted
      Nitinol meshes (internal diameter: 3.34 mm) with two different knit designs (even
      versus uneven circumferential loops) and three different wire thicknesses (0.05,
      0.0635 and 0.075 mm) under physiological conditions. The Nitinol material
      parameters were obtained from experimental testing. The compliance predicted for
      the 80-120 mmHg physiological blood pressure range was 2.5, 0.9 and 0.6%/100 mmHg
      for the even loop design and 1.2, 0.5 and 0.5%/100 mmHg for the uneven loop
      design, for wire thicknesses of 0.05, 0.0635 and 0.075 mm. The highest stress, at
      120 mmHg, was found in the even loop mesh with the thinnest wire to be 268 MPa,
      remaining 44.5% below the stress initiating stress-induced phase transformation.
      The maximum stress decreased to 132 and 91 MPa with increasing wire thickness of
      the same loop design. The uneven loop design exhibited maximum stress levels of
      65.3%, 63.6% and 87.9% of the even loop values at 0.05, 0.0635 and 0.075 mm wire
      thickness. The maximum strain of 0.7%, at 120 mmHg, remained un-critical
      considering a typical high-cycle recoverable strain of 2%. It was demonstrated
      that the numerical approach developed was feasible of effectively evaluating
      design variations of knitted Nitinol meshes towards vein graft behaviour
      equivalent to arterial mechanics.

PMID- 18328488
TI  - Analysis of the gliding pattern of the canine flexor digitorum profundus tendon
      through the A2 pulley.
AB  - Friction between a tendon and its pulley was first quantified using the concept
      of the arc of contact. Studies of human tendons conformed closely to a
      theoretical nylon cable/nylon rod model. However, we observed differences in
      measured friction that depended on the direction of motion in the canine model.
      We hypothesized that fibrocartilaginous nodules in the tendon affected the
      measurements and attempted to develop a theoretical model to explain the
      observations we made. Two force transducers were connected to each end of the
      canine flexor digitorum profundus tendon and the forces were recorded when it was
      moved through the A2 pulley toward a direction of flexion by an actuator and then
      reversed a direction toward extension. The changes of a force as a function of
      tendon excursion were evaluated in 20 canine paws. A bead cable/rod model was
      developed to simulate the canine tendon-pulley complex. To interpret the results,
      a free-body diagram was developed. The two prominent fibrocartilaginous nodules
      in the tendon were found to be responsible for deviation from a theoretical nylon
      cable gliding around the rod model, in a fashion analogous to the effect of the
      patella on the quadriceps mechanism. A bead cable/rod model qualitatively
      reproduced the findings observed in the canine tendon-pulley complex. Frictional
      coefficient of the canine flexor tendon-pulley was 0.016+/-0.005. After
      accounting for the effect created by the geometry of two fibrocartilaginous
      nodules within the tendon, calculation of frictional force in the canine tendon
      was possible.

PMID- 18328489
TI  - Contribution of vertebral [corrected] bodies, endplates, and intervertebral discs
      to the compression creep of spinal motion segments.
AB  - Spinal segments show non-linear behavior under axial compression. It is unclear
      to what extent this behavior is attributable to the different components of the
      segment. In this study, we quantified the separate contributions of vertebral
      bodies and intervertebral discs to creep of a segment. Secondly, we investigated
      the contribution of bone and osteochondral endplate (endplates including
      cartilage) to the deformation of the vertebral body. From eight porcine spines a
      motion segment, a disc and a vertebral body were dissected and subjected to
      mechanical testing. In an additional test, cylindrical samples, machined from the
      lowest thoracic vertebrae of 11 porcine spines, were used to compare the
      deformation of vertebral bone and endplate. All specimens were subjected to three
      loading cycles, each comprising a loading phase (2.0 MPa, 15 min) and a recovery
      phase (0.001 MPa, 30 min). All specimens displayed substantial time-dependent
      height changes. Average creep was the largest in motion segments and smallest in
      vertebral bodies. Bone samples with endplates displayed substantially more creep
      than samples without. In the early phase, behavior of the vertebra was similar to
      that of the disc. Visco-elastic deformation of the endplate therefore appeared
      dominant. In the late creep phase, behavior of the segment was similar to that of
      isolated discs, suggesting that in this phase the disc dominated creep behavior,
      possibly by fluid flow from the nucleus. We conclude that creep deformation of
      vertebral bodies contributes substantially to creep of motion segments and that
      within a vertebral body endplates play a major role.

PMID- 18328490
TI  - Evaluation of fracture toughness of human dentin using elastic-plastic fracture
      mechanics.
AB  - Dentin, the mineralized tissue forming the bulk of the tooth, lies between the
      enamel and the pulp chamber. It is a rich source of inspiration for designing
      novel synthetic materials due to its unique microstructure. Most of the previous
      studies investigating the fracture toughness of dentin have used linear-elastic
      fracture mechanics (LEFM) that ignores plastic deformation and could
      underestimate the toughness of dentin. With the presence of collagen
      (approximately 30% by volume) aiding the toughening mechanisms in dentin, we
      hypothesize that there is a significant difference between the fracture toughness
      estimated using LEFM (Kc) and elastic-plastic fracture mechanics (EPFM) (KJc).
      Single-edge notched beam specimens with in-plane (n=10) and anti-plane (n=10)
      parallel fractures were prepared following ASTM standard E1820 and tested in
      three-point flexure. KJc of the in-plane parallel and anti-plane parallel
      specimens were found to be 3.1 and 3.4 MPa m 1/2 and Kc were 2.4 and 2.5 MPa m
      1/2, respectively. The fracture toughness estimated based on KJc is significantly
      greater than that estimated based on Kc (32.5% on average; p<0.001). In addition,
      KJc of anti-plane parallel specimens is significantly greater than that of in
      plane parallel specimens. We suggest that, in order to critically evaluate the
      fracture toughness of human dentin, EPFM should be employed.

PMID- 18328491
TI  - Affinity capillary electrophoresis and isothermal titration calorimetry for the
      determination of fatty acid binding with beta-cyclodextrin.
AB  - Affinity capillary electrophoresis (ACE) and isothermal titration calorimetry
      (ITC) were used to investigate the binding interaction between several fatty
      acids (FAs) and beta-cyclodextrin (beta-CD). Within each method, steps taken to
      obtain accurate binding constants are discussed. The stoichiometry of interaction
      was revealed to be 1:1 regardless of FA chain length. The binding constants
      obtained using ACE were: octanoate, 6.4x10(2); 2-octenoate, 4.7x10(2); decanoate,
      3.7x10(3); 9-decenoate, 1.8x10(3) and dodecanote, 1.4x10(4). The binding
      constants obtained from ITC were of the same order of magnitude, but were
      consistently greater than those from ACE. Thermodynamic data obtained using ITC
      are used to explain the observed trends in binding strength.

PMID- 18328492
TI  - Application of linear solvation energy relationships to a custom-made polyaniline
      solid-phase microextraction fiber and three commercial fibers.
AB  - The term linear solvation energy relationships, LSERs, is considered to be a
      specific subset of a larger group of thermodynamic relationships called linear
      free energy relationships. Overall, the LSERs model represents a three-step
      thermodynamic process. The most recently accepted notation for the LSER equation,
      proposed by Abraham is given as follows: SP= c+eE+sS+aA+bB+vV where SP is any
      free energy related property of a solute, such as log K, and each term in the
      equation represents a specific type of chemical interaction. In this work, LSERs
      were applied to a custom-made polyaniline (PANI) solid-phase microextraction
      fiber and three commercial fibers immersed in water in order to aid in the
      assessment of a diverse series of solutes' partitioning behavior. By
      experimentally determining the log K for a series of solutes with known solute
      descriptors (E, S, A, B, and V) and performing multi-linear regression, the
      unknown system coefficients (e, s, a, b, and v) were obtained. The sign and
      magnitude of the system coefficients reflect the relative strengths of chemical
      interactions that affect partitioning between the two phases (fiber and water).
      The LSER study showed that the system properties having the greatest influence on
      log K were ease of cavity formation and hydrogen bond donating ability. The
      differences in dipolarity/polarizability as well as in hydrogen bond accepting
      ability further showed that all four fibers offer a unique environment for solute
      partitioning. The PANI fiber may offer greater flexibility in the choice of
      fibers to use for solid-phase microextraction.

PMID- 18328493
TI  - Functionalization of divinylbenzene/N-vinylpyrrolidone copolymer particles: ion
      exchangers for solid phase extraction.
AB  - A series of four-mixed mode ion exchangers for SPE, consisting of either weak or
      strong cation or anion exchangers, have been synthesized by functionalization of
      spherical, porous particles made from a copolymer of N-vinylpyrrolidone and
      divinylbenzene. These materials are able to selectively retain and release acidic
      and basic solutes through the judicious choice of wash solvent pH, as shown
      through the use of SPE recovery tests.

PMID- 18328494
TI  - Edge-modification of laponite with dimethyl-octylmethoxysilane.
AB  - This study examines the edge modification of laponite, with a monoalkoxy silane,
      dimethyl-octylmethoxysilane. The influence of ultrasonics, aging time and silane
      concentration on the resultant materials is examined. The silylated clays are
      characterized by XRD, IES, TGA, and Si NMR. The amount of grafted silane was
      increased by increasing the ratio of silane to clay, sonication of the reaction
      mixture and ageing the reaction mixture for no more than 24 h to avoid removal of
      grafted silane due to equilibrium effects.

PMID- 18328495
TI  - Synthesis of carboxyl-modified rod-like SBA-15 by rapid co-condensation.
AB  - Carboxyl-modified SBA-15 rod-like mesoporous materials have been synthesized by a
      facile rapid co-condensation of tetraethylorthosilicate (TEOS) and 2
      cyanoethyltriethoxysilane (CTES), followed by hydrolysis of cyanide groups in
      sulfuric acid. The concentration of carboxylic groups was varied by changing the
      silica source ratio of CTES/TEOS from 0.05 to 0.3. X-ray diffraction (XRD),
      scanning electron microscopy (SEM) and transmission electron microscopy (TEM)
      showed that the uniform ordered mesoporous structure and rod-like morphology of
      SBA-15 have been preserved even at the high concentration of carboxylic groups
      employed. Characterization by Fourier transformed infrared spectroscopy (FTIR),
      solid-state NMR investigation indicated that carboxylic groups have been
      successfully grafted onto the surface of SBA-15 through siloxane bonds
      [(O(3))SiCH(2)CH(2)COOH. The negative charges of the modified SBA-15 materials
      were enhanced by the presence of the carboxylic groups on the surface. The
      capacity of lysozyme adsorption of the modified SBA-15 materials were found to be
      significantly improved as compared with pure silica SBA-15. The maximum amount of
      lysozyme adsorption on carboxyl-modified was increased with the pH of solution
      increased from 5.5 to 9.0.

PMID- 18328496
TI  - Palladium supported on structured and nonstructured carbon: a consideration of Pd
      particle size and the nature of reactive hydrogen.
AB  - This study sets out a comprehensive characterization of bulk Pd and Pd (ca. 8%
      w/w) supported on activated carbon (AC), graphite and graphitic nanofibers (GNF).
      Catalyst activation has been examined by temperature programmed reduction (TPR)
      analysis and the activated catalysts analyzed in terms of BET area, TEM, H2
      chemisorption/TPD, and XRD measurements. While H2 chemisorption and TEM delivered
      the same sequence of increasing (surface area weighted) average Pd particle
      sizes, a significant difference (by up to a factor of 3) in the values obtained
      from both techniques has been recorded and is attributed to an unwarranted (but
      widely adopted) assumption of an exclusive H2/Pd adsorption stoichiometry=1/2. It
      is demonstrated that TEM analysis provides a valid mean particle size once it is
      established that the associated standard deviation is small and insensitive to
      additional particle counting. XRD line broadening yielded an essentially
      equivalent Pd size (20-25 nm) for each supported catalyst. The nature of the
      hydrogen associated with the supported catalysts has been probed and is shown to
      comprise of chemisorbed (on Pd), spillover (on the carbon support), and hydride
      (associated with Pd) species. Physical mixtures of bulk Pd + support (AC,
      graphite, and GNF) were also considered in order to assess hydrogen spillover by
      H2 TPD analysis. Generation of spillover hydrogen at room temperature is
      established where temperatures in excess of 740 K are required for effective
      desorption from the supported Pd catalysts, i.e., 280 K higher than that required
      for the desorption of chemisorbed hydrogen. Pd hydride formation (at room
      temperature) is shown to be reversible with decomposition occurring at ca. 380 K.
      Taking the hydrodechlorination of chlorobenzene as a test reaction, the
      capability of Pd hydride to promote a hydrogen scission of C-Cl in the absence of
      an external supply of H2 is demonstrated with a consequent consumption of the
      hydride. This catalytic response was entirely recoverable once the Pd hydride was
      replenished during a subsequent reactivation step.

PMID- 18328497
TI  - An example of combined sinoatrial and atrioventricular block.
AB  - Combined sinoatrial and atrioventricular block is rare and has been reported in
      patients on digitalis. We report a case of combined Mobitz type II sinoatrial
      block and 2:1 atrioventricular block in a patient on no medication who presented
      with recurrent syncope.

PMID- 18328498
TI  - The developmental turnpoint of orthographic consistency effects in speech
      recognition.
AB  - The influence of orthography on children's online auditory word recognition was
      studied from the end of Grade 4 to the end of Grade 9 by examining the
      orthographic consistency effect in auditory lexical decision. Fourth-graders
      showed evidence of a widespread influence of orthography in their spoken word
      recognition system; words with rimes that can be spelled in two different ways
      (inconsistent) produced longer auditory lexical decision times and more errors
      than did consistent words. A similar consistency effect was also observed on
      pseudowords. With adult listeners, on exactly the same material, we replicated
      the usual pattern of an orthographic consistency effect restricted to words in
      lexical decision. From Grade 6 onward, this adult pattern of orthographic effect
      on spoken recognition is already observable.

PMID- 18328499
TI  - A functional role for Anopheles gambiae Arrestin1 in olfactory signal
      transduction.
AB  - Insect sensory arrestins act to desensitize visual and olfactory signal
      transduction pathways, as evidenced by the phenotypic effects of mutations in the
      genes encoding both Arr1 and Arr2 in Drosophila melanogaster. To assess whether
      such arrestins play similar roles in other, more medically relevant dipterans, we
      examined the ability of Anopheles gambiae sensory arrestin homologs AgArr1 and
      AgArr2 to rescue phenotypes associated with an olfactory deficit observed in D.
      melanogaster arrestin mutants. Of these, only AgArr1 facilitated significant
      phenotypic rescue of the corresponding Drosophila arr mutant olfactory phenotype,
      consistent with the view that functional orthology is shared by these Arr1
      homologs. These results represent the first step in the functional
      characterization of AgArr1, which is highly expressed in olfactory appendages of
      An. gambiae in which it is likely to play an essential role in olfactory signal
      transduction. In addition to providing insight into the common elements of the
      peripheral olfactory system of dipterans, this work validates the importance of
      AgArr1 as a potential target for novel anti-malaria strategies that focus on
      olfactory-based behaviors in An. gambiae.

PMID- 18328500
TI  - Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased
      efficiency in the chronically infarcted rat heart.
AB  - Heart failure patients have abnormal cardiac high energy phosphate metabolism,
      the explanation for which is unknown. Patients with heart failure also have
      elevated plasma free fatty acid (FFA) concentrations. Elevated FFA levels are
      associated with increased cardiac mitochondrial uncoupling proteins (UCPs),
      which, in turn, are associated with decreased mitochondrial respiratory coupling
      and low cardiac efficiency. Here, we determined whether increased mitochondrial
      UCP levels contribute to decreased energetics in the failing heart by measuring
      UCPs and respiration in mitochondria isolated from the viable myocardium of
      chronically infarcted rat hearts and measuring efficiency (hydraulic work/O(2)
      consumption) in the isolated, working rat heart. Ten weeks after infarction,
      cardiac levels of UCP3 were increased by 53% in infarcted, failing hearts that
      had ejection fractions less than 45%. Cardiac UCP3 levels correlated positively
      with non-fasting plasma FFAs (r=0.81; p<0.01). Mitochondria from failing hearts
      were less coupled than those from control hearts, as demonstrated by the lower
      ADP/O ratio of 1.9+/-0.1 compared with 2.5+/-0.2 in controls (p<0.05). The
      decreased ADP/O ratio was reflected in an efficiency of 14+/-2% in the failing
      hearts when perfused with 1 mM palmitate, compared with 20+/-1% in controls
      (p<0.05). We conclude that failing hearts have increased UCP3 levels that are
      associated with high circulating FFA concentrations, mitochondrial uncoupling,
      and decreased cardiac efficiency. Thus, respiratory uncoupling may underlie the
      abnormal energetics and low efficiency in the failing heart, although whether
      this is maladaptive or adaptive would require direct investigation.

PMID- 18328501
TI  - HMGB1-stimulated human primary cardiac fibroblasts exert a paracrine action on
      human and murine cardiac stem cells.
AB  - High Mobility Box 1 Protein (HMGB1) is a cytokine released into the extracellular
      space by necrotic cells and activated macrophages in response to injury. We
      recently demonstrated that HMGB1 administration into the mouse heart during acute
      myocardial infarction induces cardiac tissue regeneration by activating resident
      cardiac c-kit+ cells (CSCs) and significantly enhances left ventricular function.
      In the present study it was analyzed the hypothesis that human cardiac
      fibroblasts (cFbs) exposed to HMGB1 may exert a paracrine effect on mouse and
      human CSCs. Human cFbs expressed the HMGB1 receptor RAGE. Luminex technology and
      ELISA assays revealed that HMGB1 significantly enhanced VEGF, PlGF, Mip-1alpha,
      IFN-gamma, GM-CSF, Il-10, Il-1beta, Il-4, Il-1ra, Il-9 and TNF-alpha in cFbs cell
      culture medium. HMGB1-stimulated cFbs conditioned media induced CSC migration and
      proliferation. These effects were significantly higher to those obtained when
      HMGB1 was added directly to the culture medium. In conclusion, we provide
      evidence that HMGB1 may act in a paracrine manner stimulating growth factor,
      cytokine and chemokine release by cFbs which, in turn, modulate CSC function. Via
      this mechanism HMGB1 may contribute to cardiac tissue regeneration.

PMID- 18328502
TI  - Role of gamma-subunit N- and C-termini in assembly of the mitochondrial ATP
      synthase in yeast.
AB  - The gamma-subunit is required for the assembly of ATP synthases and plays a
      crucial role in their catalytic activity. We stepwise shortened the N-terminus
      and the C-terminus of the gamma-subunit in the mitochondrial ATP synthase of
      yeast and investigated the relevance of these segments in the assembly of the
      enzyme and in the growth of the cells. We found that a deletion of 9 residues at
      the N-terminus or 20 residues at the C-terminus still allowed efficient import of
      the subunit into mitochondria; however, the assembly of both monomeric and
      dimeric holoenzymes was partially impaired. gamma-Subunits lacking 13 N-terminal
      residues or 30 C-terminal residues were not assembled. Yeast strains expressing
      either of the truncated gamma-subunits did not grow on non-fermentable carbon
      sources, indicating that non-assembled parts of the ATP synthase accumulated and
      impaired essential mitochondrial functions.

PMID- 18328503
TI  - New strategy for the generation of specific D-peptide amyloid inhibitors.
AB  - The conversion of a soluble protein into beta-sheet-rich oligomeric structures
      and further fiber formation are critical steps in the pathogenesis of the group
      of human diseases known as amyloidoses. Drugs that interfere with this process
      may thus be able to prevent and/or cure these diseases. Recent results have shown
      that short amino acid stretches can provide most of the driving force needed to
      trigger amyloid formation of a protein. These evidence suggest that compounds
      that specifically bind to peptides synthesized upon the sequence of such
      amyloidogenic protein stretches might also be able to inhibit amyloid formation
      of the corresponding full-length protein and, likely, amyloid-induced
      cytotoxicity as well. Here we present a general strategy to obtain d-peptides
      that specifically interact with protein amyloid stretches. The screening of a d
      peptide combinatorial library for inhibitors of an amyloidogenic peptide designed
      de novo has allowed us to extract a set of empirical rules for the design of d
      peptide inhibitors of any six-residue amyloidogenic stretch. d-peptides generated
      on these bases prevent amyloid formation and disassemble preformed fibrils of
      different amyloid hexapeptides identified in human amyloid proteins. In addition,
      they are also specific for their target sequence. The d-peptide designed here for
      the Alzheimer's Abeta(1-42) peptide not only inhibits and disassembles amyloid
      material but also reduces Abeta(1-42) amyloid-induced cytotoxicity in cell
      culture.

PMID- 18328504
TI  - Crystal structure of YihS in complex with D-mannose: structural annotation of
      Escherichia coli and Salmonella enterica yihS-encoded proteins to an aldose
      ketose isomerase.
AB  - The three-dimensional structure of a Salmonella enterica hypothetical protein
      YihS is significantly similar to that of N-acyl-D-glucosamine 2-epimerase (AGE)
      with respect to a common scaffold, an alpha6/alpha6-barrel, although the function
      of YihS remains to be clarified. To identify the function of YihS, Escherichia
      coli and S. enterica YihS proteins were overexpressed in E. coli, purified, and
      characterized. Both proteins were found to show no AGE activity but showed
      cofactor-independent aldose-ketose isomerase activity involved in the
      interconversion of monosaccharides, mannose, fructose, and glucose, or lyxose and
      xylulose. In order to clarify the structure/function relationship of YihS, we
      determined the crystal structure of S. enterica YihS mutant (H248A) in complex
      with a substrate (D-mannose) at 1.6 A resolution. This enzyme-substrate complex
      structure is the first demonstration in the AGE structural family, and it enables
      us to identify active-site residues and postulate a reaction mechanism for YihS.
      The substrate, beta-d-mannose, fits well in the active site and is specifically
      recognized by the enzyme. The substrate-binding site of YihS for the mannose C1
      and O5 atoms is architecturally similar to those of mutarotases, suggesting that
      YihS adopts the pyranose ring-opening process by His383 and acidifies the C2
      position, forming an aldehyde at the C1 position. In the isomerization step,
      His248 functions as a base catalyst responsible for transferring the proton from
      the C2 to C1 positions through a cis-enediol intermediate. On the other hand, in
      AGE, His248 is thought to abstract and re-adduct the proton at the C2 position of
      the substrate. These findings provide not only molecular insights into the YihS
      reaction mechanism but also useful information for the molecular design of novel
      carbohydrate-active enzymes with the common scaffold, alpha6/alpha6-barrel.

PMID- 18328505
TI  - Characterization of alkanes, hopanes, and polycyclic aromatic hydrocarbons (PAHs)
      in tar-balls collected from the East Coast of Peninsular Malaysia.
AB  - The East Coast of Peninsular Malaysia faces the South China Sea and is vulnerable
      to oil pollution because of intense petroleum production activities in the area.
      The South China Sea is also a favored route for supertankers carrying crude oil
      to the Far East. Consequently, oil spills can occur, causing pollution and
      contamination in the surrounding areas. Residual oil spills stranded on coastal
      beaches usually end up as tar-balls. Elucidating the sources of tar-balls using a
      molecular marker approach is essential in assessing environmental impacts and
      perhaps settling legal liabilities for affected parties. This study utilizes a
      multimodal molecular marker approach through the use of diagnostic ratios of
      alkanes, hopanes, and polycyclic aromatic hydrocarbons (PAHs) to determine the
      source, distribution and weathering of tar-balls. Hopane ratios (e.g., C29/C30,
      and summation C31-C35/C30 ratios) were used to identify the sources of tar-balls.
      The weathering effects were distinguished by using alkanes, namely the unresolved
      complex mixture (UCM) and low molecular weight/high molecular weight (L/H)
      ratios. Similarly, PAHs were also used for the determination of weathering
      processes undergone by the tar-balls. This multimodal molecular marker gave a
      very strong indication of the sources of tar-balls in this study. For example, 16
      out of 17 samples originated from South East Asian Crude Oil (SEACO) with one
      sample from Merang, Terengganu originating from North Sea Oil (Troll). The TRME-2
      sample may have come from a supertanker's ballast water discharge. The second
      possibility is that the tar-ball may have been transported via oceanographic
      currents. All 'weathered' sample characterizations were based on the presence of
      UCM and other ratios. The multimodal molecular marker approach applied in this
      study has enabled us to partially understand the transport behavior of tar-balls
      in the marine environment and has revealed insights into the weathering process
      of tar-balls.

PMID- 18328506
TI  - Field validation, in Scotland and Iceland, of the artificial mussel for
      monitoring trace metals in temperate seas.
AB  - The artificial mussel (AM), a novel chemical sampling device, has been developed
      for monitoring dissolved trace metals in marine environments. The AM consists of
      Chelex-100 suspended in artificial seawater within Perspex tubing and enclosed
      with semi-permeable polyacrylamide gel at both ends. To validate the field
      performance of the AM in temperate waters, we deployed AMs alongside transplanted
      blue mussels Mytilus edulis in coastal environments in Scotland (Holy Loch, Loch
      Fyne, Loch Striven and Millport) and Iceland (Reykjavikurhofn, Gufunes, South of
      thornerney, Hofsvik, Hvalfjorethur and Sandgerethi) for monitoring trace metals.
      While uptake patterns of Cd between the AM and M. edulis were highly comparable,
      discrepancies were found in the accumulation profiles of the other metals (Cu,
      Cr, Pb and Zn), in particular Zn. Nonetheless, the AMs gave a better resolution
      to accurately reveal the spatial difference in dissolved metal contamination when
      compared with M. edulis. AMs complement the use of mussels since AMs indicate
      dissolved metals in seawater, whereas uptake by mussels indicates a mixture of
      dissolved and particulate metals. Our results also indicated that historical
      metal exposure of the transplanted M. edulis could significantly confound their
      metal concentrations especially when the deployment period was short (i.e. <34d).
      This study suggested that the AM can overcome problems associated with variable
      biological attributes and pre-exposure history in the mussel, and provides a
      standardized and representative time-integrated estimate of dissolved metal
      concentrations in different marine environments.

PMID- 18328507
TI  - Evaluation of the anxiolytic-like profile of the GABAB receptor positive
      modulator CGP7930 in rodents.
AB  - There is a growing body of data to support the notion that GABA(B) receptors may
      be a therapeutic target for anxiety disorders. However, the application of
      GABA(B) receptor agonists in anxiety research and psychiatry is hampered by side
      effects that include motor in-coordination and hypothermia. Recently the GABA(B)
      receptor positive modulator GS39783 was shown to be anxiolytic in rodent models,
      but was devoid of accompanying side effects characteristic of full agonists.
      However, it is important to test whether such anxiolytic effects generalise to
      another chemical class of GABA(B) receptor positive modulators. We therefore
      aimed to investigate the anxiolytic and side-effect profile of CGP7930, the first
      reported GABA(B) receptor positive modulator, in rodent models of anxiety, motor
      coordination and hypothermia. CGP7930 (3-300 mg/kg) showed a modest, compared to
      the benzodiazepine chlordiazepoxide (10mg/kg), dose-dependent anxiolytic profile
      in the mouse stress-induced hyperthermia (100mg/kg), staircase (100 and 300
      mg/kg) and elevated zero maze tests (3-100mg/kg), but did not have any anxiolytic
      effects in the rat elevated plus maze. Similar to GS39783, CGP7930 also
      demonstrated a greatly reduced side-effect profile in comparison to the GABA(B)
      receptor full agonist baclofen in the mouse rotarod and traction wire tests and
      did not induce hypothermia. Although the effects of CGP7930 were modest, these
      results represent a second, structurally distinct, class of GABA(B) positive
      modulators showing anxiolytic activity. As such, these data support the premise
      that GABA(B) receptor positive modulation represents a novel therapeutic strategy
      for the development of anxiolytic drugs with a superior side-effect profile. The
      generation of more potent compounds is now warranted.

PMID- 18328508
TI  - Priming, response learning and repetition suppression.
AB  - Prior exposure to a stimulus can facilitate its subsequent identification and
      classification, a phenomenon called priming. This behavioural facilitation is
      usually accompanied by a reduction in neural response within specific cortical
      regions (repetition suppression, RS). Recent research has suggested that both
      behavioural priming and RS can be largely determined by previously learned
      stimulus-response associations. According to this view, a direct association
      forms between the stimulus presented and the response made to it. On a subsequent
      encounter with the stimulus, this association automatically cues the response,
      bypassing the various processing stages that were required to select that
      response during its first presentation. Here we reproduce behavioural evidence
      for such stimulus-response associations, and show the PFC to be sensitive to such
      changes. In contrast, RS within ventral temporal regions (such as the fusiform
      cortex), which are usually associated with perceptual processing, is shown to be
      robust to response changes. The present study therefore suggests a dissociation
      between RS within the PFC, which may be sensitive to retrieval of stimulus
      response associations, and RS within posterior perceptual regions, which may
      reflect facilitation of perceptual processing independent of stimulus-response
      associations.

PMID- 18328510
TI  - Action verbs and the primary motor cortex: a comparative TMS study of silent
      reading, frequency judgments, and motor imagery.
AB  - Single pulse transcranial magnetic stimulation (TMS) was applied to the hand area
      of the left primary motor cortex or, as a control, to the vertex (STIMULATION:
      TMS(M1) vs. TMS(vertex)) while right-handed volunteers silently read verbs
      related to hand actions. We examined three different tasks and time points for
      stimulation within the same experiment: subjects indicated with their left foot
      when they (i) had finished reading, (ii) had judged whether the corresponding
      movement involved a hand rotation after simulating the hand movement, and (iii)
      had judged whether they would frequently encounter the action verb in a newspaper
      (TASK: silent reading, motor imagery, and frequency judgment). Response times
      were compared between TMS(M1) and TMS(vertex), both applied at different time
      points after stimulus onset (DELAY: 150, 300, 450, 600, and 750 ms). TMS(M1)
      differentially modulated task performance: there was a significant facilitatory
      effect of TMS(M1) for the imagery task only (about 88 ms), with subjects
      responding about 10% faster (compared to TMS(vertex)). In contrast, response
      times for silent reading and frequency judgments were unaffected by TMS(M1). No
      differential effect of the time point of TMS(M1) was observed. The differential
      effect of TMS(M1) when subjects performed a motor imagery task (relative to
      performing silent reading or frequency judgments with the same set of verbs)
      suggests that the primary motor cortex is critically involved in processing
      action verbs only when subjects are simulating the corresponding movement. This
      task-dependent effect of hand motor cortex TMS on the processing of hand-related
      action verbs is discussed with respect to the notion of embodied cognition and
      the associationist theory.

PMID- 18328509
TI  - Recollection and familiarity in amnestic mild cognitive impairment: a global
      decline in recognition memory.
AB  - Despite memory failures being a central feature of amnestic mild cognitive
      impairment (a-MCI), there is limited research into the nature of the memory
      impairment associated with this condition. A further understanding could lead to
      refinement of criteria needed to qualify for this designation and aid in
      prediction of who will progress to development of clinical Alzheimer's disease.
      Dual process models posit that recognition memory is supported by the dissociable
      processes of recollection and familiarity. The present study sought to evaluate
      recognition memory in a-MCI in the framework of the dual process model. Patients
      with a-MCI and age- and education-matched controls were tested on three memory
      paradigms. Two paradigms were modifications of the process-dissociation procedure
      in which recollection required either memory of word-pair associations
      (associative) or the font color of words at study (featural). A final paradigm
      utilized the task-dissociation methodology comparing performance for item and
      visual spatial source memory. All three tasks revealed that familiarity was
      impaired to at least the same extent as recollection. As familiarity is thought
      to be spared in normal aging, its measurement may provide a relatively specific
      marker for the early pathological changes of Alzheimer's disease.

PMID- 18328511
TI  - Acute tolerance to rate-decreasing effects of single doses of ethanol.
AB  - Acute tolerance occurs when behavioral impairment is greater at a given blood
      ethanol concentration (BAC) on the ascending versus descending limb of the BAC
      time curve following administration of a single dose of ethanol, however studies
      utilizing learned behaviors have not been widely reported. We assessed acute
      tolerance to single doses of ethanol in five Lewis rats responding under a fixed
      ratio (FR8) schedule of food presentation. Response rates for food during 1-min
      components (ending 2, 4, 11, 18, 33, and 57 min after ethanol administration)
      were determined, and BAC was measured immediately after each component using a
      rat breathalyzer. Ethanol (0.4, 0.6, 0.8, and 1.2 g/kg, i.p.) produced dose
      related decreases in responding for food that tended to recover over time for all
      but the highest dose tested. Similarly, dose-related increases in BAC were also
      observed. Using either an analysis that expressed impairment per unit BAC on the
      ascending limb versus the descending limb (by assessing the area under the curve
      (AUC) for behavior and BAC on each limb), the slope of the function that relates
      the behavioral effect to BAC (each expressed as percent maximum effect), or a
      variant of the Mellanby method (hysteresis), acute tolerance was observed
      following a dose of 0.4 g/kg ethanol. Though behavior appeared to recover on the
      descending limb following higher doses (especially 0.6 and 0.8 g/kg), acute
      tolerance to these doses was not present.

PMID- 18328512
TI  - Hepatoprotective phytocompounds from Cryptomeria japonica are potent modulators
      of inflammatory mediators.
AB  - Cryptomeria japonica is an important plantation conifer tree in Asia. This study
      aimed to characterize the anti-inflammatory and hepatoprotective activities of
      the phytocompounds from C. japonica wood on LPS- or TPA-induced activation of
      proinflammatory mediators and CCl(4)-induced acute liver injury in mice. A CJH7-2
      fraction was purified from C. japonica extracts following bioactivity-guided
      fractionation, and it exhibited significant activities on inhibition of NO
      production and iNOS expression as well as up-regulating HO-1 expression in LPS
      stimulated macrophages. CJH7-2 also potently inhibits COX-2 enzymatic activity
      (IC(50)=5 microg/mL) and TPA-induced COX-2 protein expression in mouse skin
      (1mg/200 microL/site). CJH7-2 (10 mg/kg BW) can prevent CCl(4)-induced liver
      injury and aminotransferases activities in mice. Chemical fingerprinting analysis
      showed that terpenes are the major bioactive compounds in the CJH7-2 fraction.
      This is the first study to demonstrate that chemical constituents from the wood
      extract of C. japonica possess anti-inflammatory activities in vitro and in vivo
      that may play a role in hepatoprotection.

PMID- 18328513
TI  - Phytotoxic activity and conformational analysis of thymol analogs from
      Hofmeisteria schaffneri.
AB  - Bioassay-guided fractionation of two phytotoxic extracts (a CH(2)Cl(2)-MeOH (1:1)
      and an aqueous) prepared from the aerial parts of Hofmeisteria schaffneri led to
      isolation of thymol analogs 3-5, along with seven known compounds, 1, 2 and 6-10.
      Compounds 3-5 were identified by spectroscopic methods as 1,4-bis(2'-hydroxy-4'
      methylphenyl)butane-1,4-dione (3), 2-isopropyl-5-methylphenyl (2Z)-2-methylbut-2
      enoate (4) and 2-hydroxy-2-(2-hydroxy-4-methylphenyl)propane-1,3-diyl
      (2Z,2'Z)bis(2-methylbut-2-enoate) (5) and designated trivial names of
      hofmeisterins II-IV, respectively. Their conformational behavior was also studied
      by molecular modeling using density functional theory calculations at the
      B3LYP/DGDZVP level. Compounds 1-4 and 6-10 significantly inhibited radicle growth
      of seedlings of Amaranthus hypochondriacus and Echinochloa crus-galli in the
      Petri dish bioassay with IC(50)'s10(-4)M. Furthermore, the northymol analog 3
      provoked significant bleaching of seedlings of A. hypochondriacus. However, none
      of the isolates affected either seedling growth or germination of Medicago
      sativa.

PMID- 18328514
TI  - Stereochemistry of flavonoidal alkaloids from Dracocephalum rupestre.
AB  - Phytochemical studies on the aerial parts of Dracocephalum rupestre led to the
      isolation of four groups of flavonoidal alkaloids, dracocephins A-D. They were
      elucidated as conjugates of flavanone with pyrrolidin-2-one on the basis of
      extensive spectroscopic analysis. The two stereogenic centers rendered each group
      of the dracocephins as two pairs of enantiomers simultaneously. All of the
      sixteen isomers were separated successfully by chiral HPLC and their
      stereochemical features were determined by their CD data and single-crystal X-ray
      diffraction analysis of one stereoisomer. The additive relation of the
      chiroptical contributions resulting from the two stereogenic centers was
      generalized. The CD contribution of the chiral carbon in the pyrrolidin-2-one
      ring was proposed by subtraction of their respective contributions.

PMID- 18328515
TI  - Indole alkoloids from Nauclea officinalis with weak antimalarial activity.
AB  - Five indole alkaloids (naucleofficines A-E) were isolated from the stems (with
      bark) of Nauclea officinalis: (E)-2-(1-beta-d-glucopyranosyloxybut-2-en-2-yl)-3
      (hydroxymethyl)-6,7-dihydro-indolo[2,3-a]quinolizin-4(12H)-one (1), (E)-1
      propenyl-12-beta-d-glucopyranosyloxy-2,7,8-trihydro-indolo[2,3-a]pyran[3,4
      g]quinolizin-4,5(13H)-dione (2), (E)-2-(1-hydroxybut-2-en-2-yl)-11-beta-d
      glucopyranosyloxy-6,7-dihydro-indolo[2,3-a]quinolizin-4(12H)-one (3), (E)-1
      propenyl-4-hydroxy-2,4a,7,8,13b,14,14a-hepthydro
      (4alpha,4abeta,13balpha,14abeta)indolo[2,3-a]pyran[3,4-g]quinolizin-5(13H)-one
      (4) and 1-(1-hydroxyethyl)-10-hydroxy-7,8-dihydro-indolo[2,3-a]pirydine[3,4
      g]quinolizin-5(13H)-one (10-hydroxyangustoline) (5), together with two known
      compounds, naucleidinal (6) and angustoline (7). All of the structures of the
      seven compounds above were elucidated by spectroscopic methods including use of
      1D- and 2D-NMR spectroscopic analyses. Compounds 2 and 3 are rare examples of
      monoterpene indole alkaloids with a glucopyranosyloxy group attached to position
      C-12. In vitro activity screening of the above seven compounds showed weak to
      moderate inhibitory activity against Plasmodium falciparum.

PMID- 18328516
TI  - Influence sexual dimorphism on the persistence of blood parasites in infected
      Calomys callosus.
AB  - Gender has long been known to be a contributory factor in the incidence and
      progression of disorders associated with immune system disregulation. The aims of
      this experiment were to verify the influences of sexual dimorphism on the
      persistence of blood parasites out of the acute phase of infection. Male and
      female Calomys callosus were separated and infected with two strains of
      Trypanosoma cruzi, and let age until 120 days. Xenogiagnostic, culture of organs
      and blood, histopathology and lytic antibody percentages were evaluated on late
      chronic phase. Xenodiagnosis, hemoculture and lytic antibody percentages were
      positive from 45 until 120 days. For both strains in adrenal and heart,
      amastigote burdens were present until 45 days, scarcely found on 60 days and
      absent on 120 days. Steroid hormones, although having a protective role, does not
      enable animals to get completely rid of the infection. Even without showing
      apparent signs of pathological unbalance, parasites persists, hidden throughout
      the host's body.

PMID- 18328517
TI  - [Mouth floor and mobile tongue epidermoid carcinomas thickness: prognostic
      value].
AB  - INTRODUCTION: Most cancers of the oral cavity are epidermoid carcinomas. The
      prognosis is made on the patient's general health status and the tumoral stage.
      The UICC TNM staging classification system is one of the most important factors
      taken in consideration for the prognosis. But this classification in oral
      epidermoid carcinomas does not include the tumor thickness (except for T4
      tumors). Several studies demonstrated that tumor thickness could influence the
      prognosis in epidermoid carcinoma and other types of cancers. The aim of our
      retrospective study was to assess the prognostic value of tumor thickness in oral
      epidermoid carcinoma. PATIENTS AND METHODS: The study included patients with
      mouth floor or mobile tongue epidermoid carcinoma classified T1N0, T2N0 and T3N0
      between 1985 and 2005. All patients were treated with a curative intention. A
      pathologist analysed the tumor thickness and cervical lymph nodes. All the slides
      were examined to measure tumor thickness in millimetres. RESULTS: Three hundred
      and five patient files were reviewed and 124 patients were included, with 94 men
      (75.8%), and a mean age of 59.3 years (17-93). The mean and median tumor
      thickness were respectively 7.7 and 6.5 mm (0.4-30). The median tumor thickness
      was chosen for the study. There was a statistically significant link between the
      five-year probability of global survival and the initial tumor thickness and
      between neck node invasion and tumor thickness (p<0.05). DISCUSSION: This study
      suggests that tumor thickness should be taken in consideration in T1N0, T2N0 and
      T3N0 mouth floor and mobile tongue epidermoid carcinomas. In the future, the
      clinical evaluation of tumor thickness will help determine the therapeutic
      management.

PMID- 18328518
TI  - A randomised trial to assess the efficacy and safety of chlorproguanil/dapsone +
      artesunate for the treatment of uncomplicated Plasmodium falciparum malaria.
AB  - We tested the efficacy and safety of chlorproguanil/dapsone co-administered with
      artesunate (CD+A) for the treatment of uncomplicated Plasmodium falciparum
      malaria in children compared with amodiaquine+sulfadoxine/pyrimethamine (AQ+SP)
      at two different sites in Rwanda. The trial was open label and 800 patients were
      randomly assigned to AQ+SP (n=400) or CD+A (n=400). Patients were hospitalised
      for 3 days and then followed-up weekly until Day 28 after treatment. Clinical and
      parasitological outcomes were recorded. Results showed that neither treatment was
      adequately efficacious. At one site, the adequate clinical and parasitological
      response (ACPR), PCR-adjusted, was 73.3% in the CD+A arm and 87.8% in the AQ+SP
      arm (P<0.001), and at the second site the ACPR, PCR-adjusted, was 70.5% in the
      CD+A arm and 38.1% in the AQ+SP arm (P<0.001). The combination CD+A is considered
      an alternative to, or replacement for, SP in Africa because CD has been shown to
      be effective in patients for whom SP treatment has failed and, with its short
      half-life, it is expected to exert less selection pressure for resistant
      parasites than SP. However, the results of this trial indicate that in an area of
      high SP resistance, CD+A may not be the best choice.

PMID- 18328519
TI  - Six new C21 steroidal glycosides from Asclepias curassavica L.
AB  - Six new C(21) steroidal glycosides, named curassavosides A-F (3-8), were obtained
      from the aerial parts of Asclepias curassavica (Asclepiadaceae), along with two
      known oxypregnanes, 12-O-benzoyldeacylmetaplexigenin (1) and 12-O
      benzoylsarcostin (2). By spectroscopic methods, the structures of the six new
      compounds were determined as 12-O-benzoyldeacylmetaplexigenin 3-O-beta-D
      oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (3), 12-O-benzoylsarcostin 3
      O-beta-D-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (4), sarcostin 3-O
      beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D
      oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (5), sarcostin 3-O-beta-D
      oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl-(1-->4)-beta-D-canaropyranosyl
      (1-->4)-beta-D-digitoxopyranoside (6), 12-O-benzoyldeacylmetaplexigenin 3-O-beta
      D-glucopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D-canaropyranosyl
      (1-->4)-beta-d-oleandropyranosyl-(1-->4)-beta-D-digitoxopyranoside (7), and 12-O
      benzoylsarcostin 3-O-beta-D-glucopyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-
      >4)-beta-d-canaropyranosyl-(1-->4)-beta-D-oleandropyranosyl-(1-->4)-beta-D
      digitoxopyranoside (8), respectively. All compounds (1-8) were tested for in
      vitro cytotoxicity; only compound 3 showed weak inhibitory activity against Raji
      and AGZY cell lines.

PMID- 18328520
TI  - Receptor-independent, vacuolar ATPase-mediated cellular uptake of histamine
      receptor-1 ligands: possible origin of pharmacological distortions and side
      effects.
AB  - The aims of this study were to investigate whether several histamine receptor
      agonists and antagonists are subjected to receptor-independent ion trapping into
      acidic organelles, and whether this sequestration influences their
      pharmacological or toxicological properties. Vacuolar (V)-ATPase-dependent
      intracellular sequestration of agonists was recognized as morphological
      alterations (large fluid-filled vacuoles for betahistine and 1-methylhistamine,
      granular uptake for fluorescent BODIPY FL histamine) prevented by the specific V
      ATPase inhibitor bafilomycin A1 in rabbit vascular smooth muscle cells.
      Lipophilicity was the major determinant of these cellular effects (order of
      potency: BODIPY FL histamine>betahistine>1-methylhistamine>histamine) that
      occurred at high concentrations. This ranking was dissociable from the potency
      order for H(1) receptor-mediated contraction of the rabbit aorta, a response
      uninfluenced by bafilomycin. Antihistamines are inherently more lipophilic and
      caused vacuolization of a proportion of cells at 5-500 microM. Agonist or
      antagonist-induced vacuoles were of macroautophagic nature (labeled with GFP
      conjugated LC3, Rab7 and CD63; detection of LC3 II). Further, the 2 most
      lipophilic antihistamines tested, astemizole and terfenadine, were potentiated by
      V-ATPase blockade in the aortic contractility assay (13- and 3.6-fold more
      potent, respectively, pA(2) scale), suggesting that V-ATPase-mediated cation
      trapping sequesters these antagonists from the vicinity of H(1) receptors in the
      therapeutic concentration range. This potentiation did not apply to less
      lipophilic antagonists (pyrilamine, diphenhydramine). While some agonists and all
      tested antagonists of the histamine H(1) receptors induce the V-ATPase-dependent
      vacuolar and autophagic cytopathology, sequestration affects the pharmacology of
      only the most lipophilic antagonists, the ones prone to off-target arrhythmogenic
      side effects.

PMID- 18328521
TI  - Sensitivity to sodium arsenite in human melanoma cells depends upon
      susceptibility to arsenite-induced mitotic arrest.
AB  - Arsenic induces clinical remission in patients with acute promyelocytic leukemia
      and has potential for treatment of other cancers. The current study examines
      factors influencing sensitivity to arsenic using human malignant melanoma cell
      lines. A375 and SK-Mel-2 cells were sensitive to clinically achievable
      concentrations of arsenite, whereas SK-Mel-3 and SK-Mel-28 cells required
      supratherapeutic levels for toxicity. Inhibition of glutathione synthesis,
      glutathione S-transferase (GST) activity, and multidrug resistance protein (MRP)
      transporter function attenuated arsenite resistance, consistent with studies
      suggesting that arsenite is extruded from the cell as a glutathione conjugate by
      MRP-1. However, MRP-1 was not overexpressed in resistant lines and GST-pi was
      only slightly elevated. ICP-MS analysis indicated that arsenite-resistant SK-Mel
      28 cells did not accumulate less arsenic than arsenite-sensitive A375 cells,
      suggesting that resistance was not attributable to reduced arsenic accumulation
      but rather to intrinsic properties of resistant cell lines. The mode of arsenite
      induced cell death was apoptosis. Arsenite-induced apoptosis is associated with
      cell cycle alterations. Cell cycle analysis revealed arsenite-sensitive cells
      arrested in mitosis whereas arsenite-resistant cells did not, suggesting that
      induction of mitotic arrest occurs at lower intracellular arsenic concentrations.
      Higher intracellular arsenic levels induced cell cycle arrest in the S-phase and
      G(2)-phase in SK-Mel-3 and SK-Mel-28 cells, respectively. The lack of arsenite
      induced mitotic arrest in resistant cell lines was associated with a weakened
      spindle checkpoint resulting from reduced expression of spindle checkpoint
      protein BUBR1. These data suggest that arsenite has potential for treatment of
      solid tumors but a functional spindle checkpoint is a prerequisite for a positive
      response to its clinical application.

PMID- 18328522
TI  - SBTX, a new toxic protein distinct from soyatoxin and other toxic soybean
      [Glycine max] proteins, and its inhibitory effect on Cercospora sojina growth.
AB  - SBTX, a novel toxin from soybean, was purified by ammonium sulfate fractionation
      followed by chromatographic steps DEAE-Cellulose, CM-Sepharose and Superdex 200
      HR fast-protein liquid chromatography (FPLC). Lethality of SBTX to mice (LD(50)
      5.6 mg/kg) was used as parameter in the purification steps. SBTX is a 44-kDa
      basic glycoprotein composed of two polypeptide chains (27 and 17 kDa) linked by a
      disulfide bond. The N-terminal sequences of the 44 and 27kDa chains were
      identical (ADPTFGFTPLGLSEKANLQIMKAYD), differing from that of 17 kDa
      (PNPKVFFDMTIGGQSAGRIVMEEYA). SBTX contains high levels of Glx, Ala, Asx, Gly and
      Lys and showed maximum absorption at 280 nm, epsilon(1cm)(1%) of 6.3, and
      fluorescence emission in the 290-450 nm range upon excitation at 280nm. The
      secondary structure content was 35% alpha-helix, 13% beta-strand and beta-sheet,
      27% beta-turn, 25% unordered, and 1% aromatic residues. Immunological assays
      showed that SBTX was related to other toxic proteins, such as soyatoxin and
      canatoxin, and cross-reacted weekly with soybean trypsin inhibitor and
      agglutinin, but it was devoid of protease-inhibitory and hemagglutinating
      activities. The inhibitory effect of SBTX on growth of Cercospora sojina, fungus
      causing frogeye leaf spot in soybeans, was observed at 50 microg/ml,
      concentration 112 times lesser than that found to be lethal to mice. This effect
      on phytopathogenic fungus is a potential attribute for the development of
      transgenic plants with enhanced resistance to pathogens.

PMID- 18328523
TI  - Activation of spinal ERK signaling pathway contributes to pain-related responses
      induced by scorpion Buthus martensi Karch venom.
AB  - It has been demonstrated that spontaneous nociceptive behaviors, cutaneous
      hyperalgesia and paw edema can be induced by intraplantar injection of scorpion
      Buthus martensi Karch (BmK) venom in rats. In the present study, activation of
      spinal extracellular signal-regulated kinase (ERK) signaling pathway and its
      contribution to pain-related responses induced by scorpion BmK venom were
      investigated. It was found that ERK was activated not only in the superficial
      layers but also in deep layers of L4-L5 spinal cord dorsal horn, which started at
      2 min, peaked at 30-60 min and almost disappeared at 4h following intraplantar
      injection of BmK venom. Intrathecal injection of U0126 (0.1, 1.0 and 10 microg),
      a widely used specific MAP kinase kinase (MEK) inhibitor, suppressed spontaneous
      nociceptive responses and reduced primary heat hyperalgesia and bilateral
      mechanical hyperalgesia induced by BmK venom. In addition, BmK venom-induced
      spinal c-Fos expression could be inhibited by U0126 dose-dependently. Intrathecal
      delivery of NMDA receptor antagonist (5R, 10S)-(+)-5-methyl-10, 11-dihydro-5H
      dibenzo [a,d]-cyclohepten-5-10-imine hydrogen maleate (MK-801) and the non-NMDA
      receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) could partially
      inhibit activation of spinal ERK induced by BmK venom at 30 min. Thus, activation
      of ERK in spinal cord dorsal horn, partially mediated by NMDA and non-NMDA
      receptor, potentially contributes to BmK venom-induced pain-related behaviors.

PMID- 18328524
TI  - A theoretical study of ultrasonic wave transmission through a fluid-solid
      interface.
AB  - This article develops a model for the study of the transient ultrasonic waves
      radiated by a transducer in a liquid and transmitted into a solid through a plane
      interface. The method is an extension to the transient case, of the angular
      spectrum method previously developed for the monochromatic case. It is based on
      the decomposition of the ultrasonic field, in impulse plane waves. The radiated
      waveform is calculated at any point in the field by a simple summation of these
      impulse plane waves, where the propagation delay and the refraction have been
      taken into account. These plane waves are, first of all, delayed by an amount of
      time corresponding to the travel time up to the considered field point. The
      transmission through the plane interface is taken into account by using Snell
      refraction laws and transmission coefficients. In the obtained results all the
      waves previously described by other authors are highlighted: direct wave, edge
      waves, head waves as well as subsurface waves with a clear resolution between
      compression and shear waves.

PMID- 18328525
TI  - The Mamu B 17-restricted SIV Nef IW9 to TW9 mutation abrogates correct epitope
      processing and presentation without loss of replicative fitness.
AB  - CD8(+) cytotoxic T lymphocytes (CTL) play an important role in controlling virus
      replication in HIV- and SIV-infected humans and monkeys, respectively. Three well
      studied SIV CTL determinants are the two Mamu A()01-restricted epitopes Gag CM9
      and Tat SL8, and the Mamu B()17-restricted epitope Nef IW9. Point mutations
      leading to amino acid replacements in these epitopes have been reported to
      mediate SIV escape from CTL control. We found that synthetic peptides containing
      mutations in SIV Gag CM9 and Tat SL8 were no longer recognized by the respective
      CTL. On the other hand, the described I-to-T replacement at the N-terminal amino
      acid residue of the SIV Nef IW9 epitope only moderately affected CTL recognition
      of the variant peptide, TW9. In an attempt to dissect the mechanism of escape of
      the Nef TW9 mutation, we investigated the effect of this mutation on CTL
      recognition of CD4(+)T cells infected with an engineered SIV(mac)239 that
      contained the TW9 mutation in Nef. Although, the wild type and mutant virus both
      infected and efficiently replicated in rhesus macaque CD4(+)T cells, the TW9
      mutant virus failed to induce IFN-gamma expression in an SIV Nef IW9-specific CTL
      clone. Thus, unlike escape from Gag CM9- or Tat SL8-specfic CTL control
      presumably by loss of epitope binding, these results point to a defect at the
      level of processing and/or presentation of the variant TW9 epitope with resultant
      loss of triggering of the cognate TCR on CTL generated against the wild type
      peptide. Our data highlight the value of functional assays using virus-infected
      target cells as opposed to peptide-pulsed APC when assessing relevant escape
      mutations in CTL epitopes.

PMID- 18328526
TI  - AcMNPV ac143 (odv-e18) is essential for mediating budded virus production and is
      the 30th baculovirus core gene.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) ac143 (odv-e18) is
      a late gene that encodes for a predicted 9.6 kDa structural protein that locates
      to the occlusion derived viral envelope and viral induced intranuclear
      microvesicles [Braunagel, S.C., He, H., Ramamurthy, P., and Summers, M.D. (1996).
      Transcription, translation, and cellular localization of three Autographa
      californica nuclear polyhedrosis virus structural proteins: ODV-E18, ODV-E35, and
      ODV-EC27. Virology 222, 100-114.]. In this study we demonstrate that ac143 is
      actually a previously unrecognized core gene and that it is essential for
      mediating budded virus production. To examine the role of ac143 in the
      baculovirus life cycle, we used the AcMNPV bacmid system to generate an ac143
      knockout (KO) virus (AcBAC(ac142)(REP-ac143KO)). Fluorescence and light
      microscopy showed that infection by AcBAC(ac142)(REP-ac143KO) is limited to a
      single cell and titration assays confirmed that AcBAC(ac142)(REP-ac143KO) was
      unable to produce budded virus (BV). Progression to very late phases of the viral
      infection was evidenced by the development of occlusion bodies in the nuclei of
      transfected cells. This correlated with the fact that viral DNA replication was
      unaffected in AcBAC(ac142)(REP-ac143KO) transfected cells. The entire ac143
      promoter, which includes three late promoter motifs, is contained within the
      ac142 open reading frame. Different deletion mutants of this region showed that
      the integrity of the ac142-ac143 core gene cluster was required for the bacmids
      to display wild-type patterns of viral replication, BV production and RNA
      transcription.

PMID- 18328527
TI  - Multiple evaluations of the removal of pollutants in road runoff by soil
      infiltration.
AB  - Groundwater replenishment by infiltration of road runoff is expected to be a
      promising option for ensuring a sustainable urban water cycle. In this study, we
      performed a soil infiltration column test using artificial road runoff equivalent
      to approximately 11-12 years of rainfall to evaluate the removal of pollutants by
      using various chemical analyses and bioassay tests. These results indicated that
      soil infiltration treatment works effectively to remove most of the pollutants
      such as organic matter (chemical oxygen demand (CODMn) and dissolved organic
      carbon (DOC)), P species, polycyclic aromatic hydrocarbons (PAHs), numerous heavy
      metals and oestrogenic activities. Bioassay tests, including algal growth
      inhibition test, Microtox and mutagen formation potential (MFP) test, also
      revealed effective removal of toxicities by the soils. However, limited amounts
      of NO3, Mn, Ni, alkaline earth metals, perfluorooctane sulphonate (PFOS) and
      perfluorooctane sulphonamide (FOSA) were removed by the soils and they possibly
      reach the groundwater and cause contamination.

PMID- 18328528
TI  - Ranking tributaries for setting remediation priorities in a TMDL context.
AB  - The San Joaquin River (SJR) in the Central Valley of California has been
      designated an impaired waterbody based on its loss of fisheries-related
      beneficial uses and the river is now subject to regulation under total maximum
      daily load (TMDL) rules. For impaired waterbodies, numeric standards alone may
      not be sufficient to establish remediation priorities and priorities must be
      established by comparing drainages to each other. Data collected as part of
      regional water quality (WQ) studies in the SJR Valley were not normally
      distributed, so nonparametric methods based on ranking were used to compare the
      WQ of individual tributaries and drainages. Normalized rank means (NRMs) were
      calculated from ranked data and NRMs were mapped to identify priority drainages
      for WQ improvement activities. NRMs for individual parameters were combined into
      indexes that are useful for examining the relative importance of different
      drainages for multiple parameters simultaneously. Indexes were developed for
      eutrophication and overall WQ. This ranking approach is being proposed as an
      easily understood, transparent, and scientifically rigorous method to assess the
      relative WQ impact of individual drainages and set watershed remediation
      priorities.

PMID- 18328529
TI  - Geochemical characterization of PM10 emitted by glass factories in Murano, Venice
      (Italy).
AB  - The atmosphere in Venice, like in other European cities, is influenced by complex
      PM(10) multi-emission sources with a net tendency to exceed the limits fixed by
      the directive 99/30/EC. This study investigated the composition of an ensemble of
      similar industrial sources, the Murano Glassmaking Factories (MGFs), and their
      influence on the Venice air quality, using a modelling approach, statistical
      analysis and geochemical considerations. Preliminary modelling simulations were
      conducted to select three sampling sites along the way of preferential transport
      of pollutants from source between February and April 2003. Subsequently, a
      sampling campaign was carried out in the same period of simulations.
      Concentrations of PM(10), eight major elements (Al, Ti, Ca, Mg, Na, K, Fe, Mn),
      20 minor and trace elements (Li, V, Cr, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Ru,
      Rh, Cd, Sb, Ba, Ce, Pt, Pb) and four PAHs (BaA, BbF, BkF, BaP) were quantified.
      The analytical results were statistically processed for exploring the
      relationships between inorganic elements and organic compounds, and results were
      interpreted using geochemical considerations. Results show a MGF component of
      PM(10) characterised by two different fingerprints: the first linked to glass raw
      material composition and the second mainly related to glass additives.
      Particularly, Cd, Se, As and Li preserve their ratios in all study area, and are
      interpreted as principal components of the MGF emissions. Other fingerprints can
      be traced to urban sources from the Venetian mainland.

PMID- 18328530
TI  - Concentrations of polybrominated diphenyl ethers, organochlorine compounds and
      nitro musks in mother's milk from Germany (Bavaria).
AB  - The aim of this study was to determine a new spectrum of substances that will be
      selected for future breast milk monitoring in Bavaria, Germany. Up to now, the
      analysis of breast milk in Bavaria was limited to selected organochlorine
      pesticides (OCP) and polychlorinated biphenyls (PCB). Information on background
      levels of toxicologically interesting substances, such as dioxins and dioxin-like
      polychlorinated biphenyls (dl-PCB) or on flame retardants, such as polybrominated
      diphenyl ethers (PBDE) are very limited or not available for Bavaria. We present
      here levels on OCP, some nitro musks, indicator PCB, polychlorinated dibenzo-p
      dioxins (PCDD), polychlorinated dibenzofurans (PCDF) and dl-PCB concentrations in
      breast milk collected at 12 weeks post-partum of 43 primiparous mothers living in
      Bavaria. The average concentrations of PCDD, PCDF and dl-PCB were 4.98, 4.93 and
      9.92 pg WHO-TEQ g(-1) lipid, respectively. The mean contribution of PCDD, PCDF,
      non-ortho and mono-ortho PCB to the total WHO-TEQ is consistently about 25% each.
      Furthermore the concentration on PBDE in breast milk at two sampling points, 12
      weeks and 16 weeks after delivery, were determined. Overall, 19 PBDE congeners
      were analysed, however the level of 12 PBDE congeners were below the limit of
      detection. BDE-153 and BDE-47 were the predominant congeners accounting for about
      66% of the total PBDE. The means of the total concentrations of PBDE (five
      congeners) at the first and second sampling point were 1.90 and 2.03 ng g(-1)
      lipid, respectively. Based on our results the overall concentrations of the
      analysed substances in milk samples from Bavaria are consistent with the levels
      of breast milk samples of other European countries reflecting the low background
      body burden of these compounds.

PMID- 18328531
TI  - Effect of preozonation on the characteristic transformation of fulvic acid and
      its subsequent trichloromethane formation potential: presence or absence of
      bicarbonate.
AB  - The effects of bicarbonate on the characteristic transformation of fulvic acid
      (FA) and its subsequent trichloromethane formation potential (TCMFP) were
      investigated in the process of preozonation. Dissolved organic carbon (DOC)
      removal rate and the residual aqueous ozone concentration during preozonation
      were measured with different bicarbonate concentration. The presence of
      bicarbonate inhibited DOC removal and decreased TCMFP yields in the initial
      oxidation period. In order to explain these phenomena, the molecular weight (MW)
      distribution (<5, 5-10, 10-30, and >30 kDa) and corresponding TCMFP were
      investigated for FA and its subsequent oxidation products. Furthermore,
      transformation of molecular structure, based on MW distribution, was also
      characterized with Fourier transform infrared (FTIR) spectrum. Bicarbonate showed
      different inhibiting effects on TCMFP of organic species with different MW, and
      more significant TCMFP decrement was observed for the high MW fraction (>30 kDa)
      than for the low MW fractions. Preozonation led to obvious reduction on DOC and
      UV254 in most of MW fractions wherever bicarbonate was present or not,
      demonstrating that ozone contributed to both organics mineralization and
      structure variation, synchronously. As being indicated from the results of FTIR
      and gas chromatography-mass spectrometry, the functional groups such as alcohols,
      epoxides and phenols, the formation of which was promoted with hydroxyl radicals
      (.OH) and would be remarkably inhibited by bicarbonate, were responsible for the
      increment of TCM precursor's concentration during ozonation. Results of these
      studies confirmed low dosage bicarbonate affecting the ozonation pathways,
      influencing the intermediate species formation and impacting its subsequent TCMFP
      yields through inhibiting the .OH radicals reactions mainly occurred in high MW
      fractions.

PMID- 18328532
TI  - Effects of environmental contaminants on hemoglobin of larvae of aquatic midge,
      Chironomus riparius (Diptera: Chironomidae): a potential biomarker for
      ecotoxicity monitoring.
AB  - The effects of environmental contaminants (i.e., nonylphenol, bisphenol A
      diglycidyl ether, benzo[a]pyrene, chlorpyriphos, paraquat dichloride, and lead
      nitrate) on Chironomus hemoglobin were investigated in the 4th instar larvae of
      Chironomus riparius (Diptera: Chironomidae), with respect to the total hemoglobin
      contents, individual globin gene expression, individual globin protein expression
      and hemoglobin oxidation. In our studies, 7 and 6 globin isoforms were
      preliminarily characterized by molecular weight and isoelectric point,
      respectively, in the 4th instar larvae of C. riparius. Most chemicals were unable
      to modify the total hemoglobin contents, however, the expression patterns of the
      globin transcript and proteins suggest that C. riparius globin exists in both
      inducible and consecutively expressed forms, with multiplicity that may allow
      this animal to better adapt toward stressful environmental conditions, including
      pollution stress. The oxyhemoglobin was observed to be downregulated in C.
      riparius on exposure to bisphenol A and chlorpyriphos, probably reflecting its
      increased autoxidation to methemoglobin. The overall results would suggest that
      globin can be a target molecule of environmental contaminants, and of the tested
      parameters, the alteration of individual globin levels (i.e., mRNA or protein
      levels) may have potential for the development of a biomarker for ecotoxicity
      monitoring.

PMID- 18328533
TI  - On the dissolution kinetics of humic acid particles. Effect of monocarboxylic
      acids.
AB  - The dissolution kinetics of humic acid particles has been studied in batch
      experiments, and the effects of monocarboxylic (formic, acetic, and propionic)
      acids are reported. The dissolution rate of the particles is significantly
      affected by the presence of monocarboxylic acids in the pH range 4-10. At pH 7,
      for example, propionic acid increases 30 times this dissolution rate. The
      capacity of increasing the dissolution rate is in the order formic acid<acetic
      acid<propionic acid, and this dissolving capacity of carboxylics seems to be
      directly related to their affinity for HA molecules located at the surface of the
      solid particles. The results indicate that carboxylics and related compounds may
      affect markedly the mobility and transport of humic substances in the
      environment.

PMID- 18328534
TI  - Enhanced coagulation with polyaluminum chlorides: role of pH/alkalinity and
      speciation.
AB  - Enhanced coagulation is considered to be among the best available techniques
      (BAT) for disinfection by-product (DBP) precursor removal in water treatment.
      Improving existing understanding requires further consideration of nuances of
      chemical speciation relative to source water chemistry. In this paper, the effect
      of alkalinity/pH and speciation on inorganic polymer flocculants, polyaluminum
      chlorides (PACls) for enhanced particle and natural organic matter (NOM) removal
      was investigated. Three kinds of well-characterized typical source waters in
      China with low, moderate, and high alkalinity were selected. Performance of
      coagulants is controlled not only by preformed species but also by those formed
      in situ. At neutral and basic pH values, PACls with higher basicity (ratio of OH(
      )/Al), which have more stable preformed Alb (the rapid reacted species as in
      ferron assay), are more efficient for turbidity and NOM removal. At slightly
      acidic pH, PACls with lower basicity are more efficient since more Alb can be
      formed in situ. Optimal NOM removal was achieved at pH 5.5-6.5 for all PACls.
      Basicity, speciation, and dosage of coagulant should be optimized based on raw
      water alkalinity to enhance the removal efficiency of NOM.

PMID- 18328535
TI  - Enhanced sludge solubilization by microbubble ozonation.
AB  - A microbubble ozonation process for enhancing sludge solubilization was proposed
      and its performance was evaluated in comparison to a conventional ozone bubble
      contactor. Microbubbles are defined as bubbles with diameters less than several
      tens of micrometers. Previous studies have demonstrated that microbubbles could
      accelerate the formation of hydroxyl radicals and hence improve the ozonation of
      dyestuff wastewater. The results of this study showed that microbubble ozonation
      was effective in increasing ozone utilization and improving sludge
      solubilization. For a contact time of 80 min, an ozone utilization efficiency of
      more than 99% was obtained using the microbubble system, while it gradually
      decreased from 94% to 72% for the bubble contactor. The rate of microbial
      inactivation was obviously faster in the microbubble system. At an ozone dose of
      0.02g O(3)g(-1) TSS, about 80% of microorganisms were inactivated in the
      microbubble system, compared with about 50% inactivation for the bubble
      contactor. Compared to the bubble contactor, more than two times of COD and total
      nitrogen, and eight times of total phosphorus content were released from the
      sludge into the supernatant by using the microbubble system at the same ozone
      dosage. The application of microbubble technology in ozonation processes may
      provide an effective and low cost approach for sludge reduction.

PMID- 18328536
TI  - Accelerated seeded precipitation pre-treatment of municipal wastewater to reduce
      scaling.
AB  - Membrane based treatment processes are very effective in removing salt from
      wastewater, but are hindered by calcium scale deposit formation. This study
      investigates the feasibility of removing calcium from treated sewage wastewater
      using accelerated seeded precipitation. The rate of calcium removal was measured
      during bench scale batch mode seeded precipitation experiments at pH 9.5 using
      various quantities of calcium carbonate as seed material. The results indicate
      that accelerated seeded precipitation may be a feasible option for the decrease
      of calcium in reverse osmosis concentrate streams during the desalination of
      treated sewage wastewater for irrigation purposes, promising decreased incidence
      of scaling and the option to control the sodium adsorption ratio and nutritional
      properties of the desalted water. It was found that accelerated seeded
      precipitation of calcium from treated sewage wastewater was largely ineffective
      if carried out without pre-treatment of the wastewater. Evidence was presented
      that suggests that phosphate may be a major interfering substance for the seeded
      precipitation of calcium from this type of wastewater. A pH adjustment to 9.5
      followed by a 1-h equilibration period was found to be an effective pre-treatment
      for the removal of interferences. Calcium carbonate seed addition at 10 g l(-1)
      to wastewater that had been pre-treated in this way was found to result in
      calcium precipitation from supersaturated level at 60 mg l(-1) to saturated level
      at 5 mg l(-1). Approximately 90% reduction of the calcium level occurred 5 min
      after seed addition. A further 10% reduction was achieved 30 min after seed
      addition.

PMID- 18328537
TI  - Evaluation of the impact of various agricultural practices on nitrate leaching
      under the root zone of potato and sugar beet using the STICS soil-crop model.
AB  - The quaternary aquifer of Vitoria-Gasteiz (Basque Country, Northern Spain) is
      characterised by a shallow water table mainly fed by drainage water, and thus
      constitutes a vulnerable zone in regards to nitrate pollution. Field studies were
      performed with a potato crop in 1993 and a sugar beet crop in 2002 to evaluate
      their impact on nitrate leaching. The overall predictive quality of the STICS
      soil-crop model was first evaluated using field data and then the model was used
      to analyze dynamically the impacts of different crop management practices on
      nitrate leaching. The model was evaluated (i) on soil nitrate concentrations at
      different depths and (ii) on crop yields. The simulated values proved to be in
      satisfactory agreement with measured values. Nitrate leaching was more pronounced
      with the potato crop than with the sugar beet experiment due to i) greater
      precipitation, ii) lower N uptake of the potato crop due to shallow root depth,
      and iii) a shorter period of growth. The potato experiment showed that excessive
      irrigation could significantly increase nitrate leaching by increasing both
      drainage and nitrate concentrations. The different levels of N-fertilization
      examined in the sugar beet study had no notable effects on nitrate leaching due
      to its high N uptake capacity. Complementary virtual experiments were carried out
      using the STICS model. Our study confirmed that in vulnerable zones agricultural
      practices must be adjusted, that is to say: 1) N-fertilizer should not be applied
      in autumn before winter crops; 2) crops with low N uptake capacity (e.g.
      potatoes) should be avoided or should be preceded and followed by nitrogen catch
      crops or cover crops; 3) the nitrate concentration of irrigation water should be
      taken into account in calculation of the N-fertilization rate, and 4) N
      fertilization must be precisely adjusted in particular for potato crops.

PMID- 18328538
TI  - Antibodies to oxidized LDL/beta2-glycoprotein I in antiphospholipid syndrome
      patients with venous and arterial thromboembolism.
AB  - It has been reported that IgG to oxidized LDL/beta2-glycoprotein I
      (oxLDL/beta2GPI) complexes are associated with arterial thromboembolism (TE) in
      patients with antiphospholipid syndrome (APS). How these antibodies behave in
      arterial as compared to venous TE in APS is unknown. The aim of the present study
      was to evaluate the association of IgG anti-oxLDL/beta2GPI with clinical
      manifestations in category I APS patients. Fifty-seven APS patients with triple
      positivity (Lupus Anticoagulant (LAC), anti cardiolipin (aCL) and anti-beta2
      glycoprotein I (abeta2GPI) antibodies), 28 with arterial and 29 with venous
      thromboembolism, were included in the study. There were no differences in the
      dRVVT ratio, IgG/IgM aCL and IgG/IgM abeta2GPI titers in the two patient groups.
      There were no differences in the IgG (78.5 U+/-59.8 vs. 112.2 U+/-92.3) and IgM
      (16.3 U+/-15.9 vs. 21.1 U+/-14.3) anti-oxLDL/beta2GPI mean values. A significant
      correlation was found between IgG anti-oxLDL/beta2GPI and IgG anti-beta2GPI
      titers in the whole group of APS patients. Patients in the arterial group were
      older and had more risk factors for atherosclerosis. Data from this study do not
      support the hypothesis that IgG anti-oxLDL/beta2GPI are specifically associated
      to arterial TE in Category I APS patients.

PMID- 18328539
TI  - Identification of residues of functional importance within the central turn
      motifs present in the cytoplasmic tails of integrin alphaIIb and alphaV subunits.
AB  - INTRODUCTION: Previous studies demonstrated that cell-permeable alphaIIb
      cytoplasmic peptides can modulate the activation of alphaIIbbeta3. An integrin
      activation motif was mapped to its membrane proximal region and a double proline
      mutant peptide and receptor indicated that its central turn motif had inhibitory
      capacity. However, the residues critical for inhibition of alphaIIbbeta3
      activation were not identified. Using central turn peptides derived from alphaIIb
      and alphaV, residues critical for suppression of integrin activation were
      identified and the importance of these residues in protein-protein interactions
      was assessed. MATERIALS AND METHODS: Cell-permeable peptides were used to
      determine the capacity of the central turn peptides to suppress alphaIIbbeta3 and
      alphaVbeta3 activation. Far Western analysis was used to characterize the
      capacity of the peptides to interact with CIB1 and surface plasmon resonance was
      used to characterize the binding of an antibody to the cytoplasmic tails of
      alphaIIb and alphaV. RESULTS AND CONCLUSIONS: The central turn peptide from
      alphaV, alphaV(993-1001), has full inhibitory capacity while that derived from
      alphaIIb requires additional residues located adjacent to alphaIIb(995-1003).
      Within these two sequences there is a switch in the position of an asparaginine
      and leucine residue for a valine and glutamine (alphaIIb, RNRPPLEED; alphaV,
      RVRPPQEEQ). This switch had a dramatic effect on their inhibitory capacity and on
      protein-protein interactions. The two arginine and glutamic residues,
      juxtapositioned at identical locations in both subunits, appeared to be important
      in specifying the orientation by which proteins can dock to this region in
      alphaIIb and alphaV.

PMID- 18328540
TI  - The thrombolytic effect of miniplasmin in a canine model of femoral artery
      thrombosis.
AB  - BACKGROUND AND PURPOSE: Miniplasmin was a des-kringle variant of plasminogen with
      potential pharmacological application. We investigated the thrombolytic effect of
      miniplasmin in a canine model of femoral artery thrombosis. METHODS: In
      anesthetized dogs, a stable occlusive thrombus was formed by mechanical and
      electrolytic injury of the vessel wall, that the animals were later injected with
      miniplasmin (0.75 mg/kg, 1.5 mg/kg and 3.0 mg/kg, i.a.) and rt-PA (0.5 mg/kg,
      i.a.) intra-arterially. Hemodynamic parameters and hemorrhage status were
      monitored for 2 h. Thrombin time, activated partial thromboplastin time,
      prothrombin time and fibrinogen concentration were tested at 2 h after
      administration. Fibrin degradation product and D-dimer concentration were tested
      by ELISA. RESULTS: The incidence of reperfusion in the miniplasmin (3.0 and 1.5
      mg/kg) groups was 100%, and time to reperfusion was (3.3+/-1.0) and (7.0+/-2.3)
      min, which was shorter than rt-PA. After reperfusion, none of the vessels in the
      miniplasmin (1.5 and 3.0 mg/kg) groups reoccluded, whereas 20% of vessels
      reoccluded in the rt-PA group. Rudimental thrombus mass in the miniplasmin (1.5
      and 3.0 mg/kg) groups were smaller than rt-PA. The operative wounds in all
      miniplasmin groups had no hemorrhage within 2 h. There were no significant
      differences in thrombin time, activated partial thromboplastin time and
      prothrombin time. Fibrinogen concentration in the miniplasmin (3.0 mg/kg) group
      reduced significantly as compared with baseline and thrombosis values, whereas
      these values in the miniplasmin (1.5 and 0.75 mg/kg) groups were unchanged.
      Fibrin degradation product and D-dimer concentration increased significantly
      after thrombolysis. CONCLUSIONS: The results suggest that miniplasmin may be
      useful for the treatment of thrombosis and without complication of hemorrhage.
      This is in contrast to rt-PA, which intrinsically has a higher risk of occurring
      the hemorrhage risk.

PMID- 18328541
TI  - Prevalence of renal failure and use of antithrombotic prophylaxis among medical
      inpatients at increased risk of venous thromboembolic events.
AB  - BACKGROUND: Evidence-based guidelines recommend the use of antithrombotic
      prophylaxis in medical patients at risk of venous thromboembolism (VTE). Low
      molecular weight heparins (LMWHs) are usually preferred to unfractionated
      heparin. However, when prophylactic doses of LMWH are administered, patients with
      renal failure (RF) are exposed to the risk of excessive accumulation, and thus to
      an increased risk of bleeding. We aimed to assess the prevalence of RF among
      medical inpatients at increased risk of VTE and the use and dosage of
      antithrombotic prophylaxis in these patients. METHODS: In a cross sectional study
      carried out at three different hospitals, information on all medical inpatients
      was collected. Patients were defined at increased risk of VTE according to the
      American College of Chest Physicians guidelines. Data on the proportion of
      patients with renal RF, on the use and dosage of antithrombotic prophylaxis, and
      on the presence of contraindications to antithrombotic therapy were ascertained.
      RESULTS: 439 hospital charts were examined; 158 patients (36.0%) were defined at
      increased risk of VTE and had no contraindications to antithrombotic treatment.
      Thromboprophylaxis was prescribed to 61.4% of these patients. Eighty (50.7%) of
      them also had moderate or severe RF. There was no difference in the rate of
      prescription nor in the doses of antithrombotic prophylaxis between patients with
      and without RF (p=0.81 and p=0.94, respectively). CONCLUSIONS: RF is frequently
      present in medical patients at risk of VTE. A considerable proportion of these
      patients may not receive the optimal type or dose of antithrombotic prophylaxis.

PMID- 18328542
TI  - Prescription narcotic drug abuse: "We have met the enemy and they are
      ourselves.".

PMID- 18328544
TI  - A multiarray electrode mapping method for percutaneous thermocoagulation as
      treatment of trigeminal neuralgia. Technical note on a series of 178 consecutive
      procedures.
AB  - BACKGROUND: We describe our method and mapping technique of the trigeminal nerve
      using a quadripolar electrode to minimize morbidity of percutaneous
      thermocoagulation as treatment of trigeminal neuralgia. METHOD: Of 381 patients
      selected for postgasserian thermocoagulation, 178 consecutive procedures were
      carried out using, in most cases, our painless and ambulatory method and
      technique. All patients were preoperatively subjected to 3-dimensional
      constructive interference in steady-state magnetic resonance and magnetic
      resonance angiography. Transgasserian introduction of our quadripolar multiarray
      electrode under constant fluoroscopic monitoring is used with systematic
      recording of radiologic angles at, in front of, and behind the clivus profile,
      always below the selar floor. The individual's somatotopic map based on the
      verbal responses of 34 facial subsegments in lieu of the usual 3 is carefully
      established. Lesions are aimed at the trigger of pain and restricted to fibers
      with the lowest thresholds. Maximal lesions are one third the size used in
      conventional thermocoagulation. Lesions attempt to avoid damage to the first
      division, uninvolved fibers, and the motor division. RESULTS: Pre- and
      postoperatory thresholds demonstrate that trigger-aimed small lesions do not
      extend to unwanted subsegments. The described technique can minimize unnecessary
      complications from percutaneous thermocoagulation.

PMID- 18328546
TI  - Mixed-density extradural hematomas on computed tomography-prognostic
      significance.
AB  - BACKGROUND: It has been variably reported that patients who acutely present with
      low- or mixed-density blood on CT scan are associated with poor clinical outcome.
      The aim of the study was to correlate the presence or absence of mixed density
      within EDHs on CT scanning with the clinical outcome. METHODS: This is a
      retrospective study of a total of 109 patients with EDHs who were operated on
      from August 2001 to August 2002. The CT scans were reviewed and classified into 2
      categories-predominantly hyperdense and mixed density. This was correlated with
      clinical details and outcome. RESULTS: In all, 43.2% (16/37) of patients in the
      mixed-density category presented with GCS of no more than 8 as compared with
      23.6% (17/72) of patients in the hyperdense group (P < .05). Mean hematoma volume
      in the mixed-density group was 72 cm(3) as compared with 42 cm(3) in the
      hyperdense group (P < .05). Mortality rate was significantly higher in the mixed
      density category (21.6% vs 4.2%, P < .05). CONCLUSION: The study portends mixed
      density in EDH as a potent poor prognostic indicator. The mixed density of the
      clot probably indicates that the clot is rapidly increasing in size and requires
      even earlier and more aggressive treatment.

PMID- 18328548
TI  - Impact of a program for the prevention of traffic accidents in a Southern
      Brazilian city: a model for implementation in a developing country.
AB  - BACKGROUND: Traffic accidents constitute the main cause of death in the first
      decades of life. Traumatic brain injury is the event most responsible for the
      severity of these accidents. The SBN started an educational program for the
      prevention of traffic accidents, adapted from the American model "Think First" to
      the Brazilian environment, since 1995, with special effort devoted to the
      prevention of TBI by using seat belts and motorcycle helmets. The objective of
      the present study was to set up a traffic accident prevention program based on
      the adapted Think First and to evaluate its impact by comparing epidemiological
      variables before and after the beginning of the program. METHODS: The program was
      executed in Maringa city, from September 2004 to August 2005, with educational
      actions targeting the entire population, especially teenagers and young adults.
      The program was implemented by building a network of information facilitators and
      multipliers inside the organized civil society, with widespread population
      dissemination. To measure the impact of the program, a specific software was
      developed for the storage and processing of the epidemiological variables.
      RESULTS: The results showed a reduction of trauma severity due to traffic
      accidents after the execution of the program, mainly TBI. CONCLUSIONS: The
      adapted Think First was systematically implemented and its impact measured for
      the first time in Brazil, revealing the usefulness of the program for reducing
      trauma and TBI severity in traffic accidents through public education and
      representing a standardized model of implementation in a developing country.

PMID- 18328549
TI  - Ovarian cancer immuno-reactive antigen domain containing 1 (OCIAD1), a key player
      in ovarian cancer cell adhesion.
AB  - OBJECTIVES: To identify proteins unique to metastatic ovarian cancer and test
      their potential involvement in cell adhesion. METHODS: We purified plasma
      membrane from paired metastatic and primary tumor tissues from patients with
      stage IIIC ovarian cancer. Membrane proteins unique to metastases were identified
      by liquid chromatographic mass spectrometry (LC-MS). The role of one of the
      identified proteins, ovarian cancer immuno-reactive antigen domain containing 1
      (OCIAD1) in cell adhesion was determined in the presence of LPA using both over
      expression and down regulation approaches. RESULTS: We identified a
      differentially expressed 29 kDa protein as OCIAD1 over-expressed in metastatic
      tissues, when compared to primary tumor tissues. OCIAD1 over-expression in HEY
      ovarian cancer cells increased LPA-induced, but not basal level cell adhesion to
      extracellular matrix proteins collagen I and laminin 10/11. This enhancement was
      not blocked by LY294002 and GF109203X, suggesting that OCIAD1 does not use PKC
      and PI3K signaling pathways to exert its effect on adhesion. In addition, LPA
      induced cell adhesion to collagen I was unaffected by paclitaxel (5 microM) in
      OCIAD1 overexpressing cells. CONCLUSIONS: This is the first report that OCIAD1 is
      over-expressed in metastatic ovarian cancer tissues. The effect of OCIAD1 on cell
      adhesion may be related to its function in ovarian cancer. Failure of paclitaxel
      to affect ovarian cancer cell adhesion in presence of OCIAD1 raises the
      possibility of OCIAD1's role in tumor metastasis. Ongoing studies using a mouse
      orthotopic LPA-dependent ovarian cancer metastasis model are focused on
      strategies to inhibit the potential role of OCIAD1 in tumor metastasis.

PMID- 18328551
TI  - Overlapping, but not identical, discriminative stimulus effects of the
      neuroactive steroid pregnanolone and ethanol.
AB  - Many behavioral effects of neuroactive steroids are mediated by GABA(A)
      receptors; however, other receptors might be involved. Ethanol has a complex
      mechanism of action, and many of the same receptors have been implicated in the
      effects of neuroactive steroids and ethanol. The goal of this study was to
      determine whether actions of neuroactive steroids and ethanol at multiple
      receptors result in similar discriminative stimulus effects. Rats discriminated
      5.6 mg/kg of pregnanolone while responding under a fixed-ratio 20 schedule of
      food presentation. Pregnanolone, flunitrazepam and pentobarbital produced >80%
      pregnanolone-lever responding. In contrast, neither morphine nor the negative
      GABA(A) modulator beta-CCE substituted for pregnanolone up to doses that markedly
      decreased response rates. Ethanol substituted only in some rats; in other rats,
      ethanol produced <20% pregnanolone-lever responding up to rate-decreasing doses.
      Thus, substitution of positive GABA(A) modulators, and not morphine or beta-CCE,
      for pregnanolone in all rats suggests that positive modulation of GABA(A)
      receptors is important in the discriminative stimulus effects of pregnanolone.
      Although pregnanolone might have actions at other receptors, in addition to
      actions at GABA(A) receptors, substitution of ethanol for pregnanolone only in
      some rats suggests that the mechanisms of action of pregnanolone and ethanol
      overlap, but are not identical.

PMID- 18328552
TI  - The development of a Chinese version of the tobacco use subscale of the
      behavioral risk factor surveillance system (BRFSS).
AB  - OBJECTIVES: To provide a culturally and linguistically specific survey instrument
      for tobacco consumption in Taiwan, we evaluated the reliability and validity of a
      Chinese translation of the 1993 US Tobacco Use Subscale of Behavioral Risk Factor
      Surveillance System (TU-BRFSS). METHODS: An integrative translation was followed
      by a pilot study of 100 randomly selected adults from throughout Taiwan.
      Telephone interviews took place in July, 2004. Validity was assessed by Content
      Validity Index (CVI) computed on the basis of expert review and the averaged
      scores of back-translation. RESULTS: Of 29 questions, 25 met the CVI criteria for
      retention in the instrument. In the back-translation assessment, 85% of the
      average scores taken from the expert evaluations were above 4 (scale of 1-5).
      Three of four percent agreements between the referent question and 4 other
      questions were 100%. CONCLUSIONS: The Chinese version of the TU-BRFSS, with
      appropriate content, semantics, and conceptual equivalence, appears valid and
      reliable for future surveillance and research in Taiwan and other Chinese
      populations.

PMID- 18328553
TI  - The role of water mass dynamics in controlling bacterial abundance and production
      in the middle Adriatic Sea.
AB  - Month-to-month fluctuations in the abundance of bacteria and heterotrophic
      nanoflagellates (HNF) and bacterial production, as well as various chemical
      (nutrients, oxygen) and physical (salinity, temperature) parameters were analysed
      at a station located in the open middle Adriatic Sea during one decade (1997
      2006). Being influenced by both coastal waters and open Adriatic circulation in
      the surface layer, and by the deep Adriatic water masses in the deep layers (100
      m), this station is quite suitable for detecting the environmental changes
      occurring in the open Adriatic Sea with respect to the circulation of its water
      masses and their long-term changes and anomalies. Multivariate methods were used
      to identify seasonal and inter-annual changes of the investigated parameters,
      associating observed changes to the changes in Adriatic water masses and
      circulation regimes. The analyses showed that bacterial abundance and production
      were controlled by different water mass dynamics during 1997-2001 compared to
      2002-2006 period, particularly noticeable in different seasonal patterns of
      biological parameters. The interplay between North Adriatic Dense Water (NAdDW)
      and Levantine Intermediate Water (LIW) resulted in a change in the available
      nutrients (NAdDW is poor in orthophosphates), and as a consequence different
      bacterial abundance and production. A few periods were examined in detail, such
      as 2004, when LIW inflow was particularly strong and was accompanied by an
      increase of bacterial and HNF abundances, as well as of bacterial production.

PMID- 18328554
TI  - Spatial variation of metal bioaccumulation in the hydrothermal vent mussel
      Bathymodiolus azoricus.
AB  - The variability of the bioaccumulation of metals (Ag, Cd, Cu, Fe, Mn and Zn) was
      extensively studied in the mussel Bathymodiolus azoricus from five hydrothermal
      vent sites inside three main vent fields of increasing depth along the Mid
      Atlantic Ridge: Menez Gwen, Lucky Strike and Rainbow. Metal bioaccumulation
      varied greatly between vent fields and even between sites inside a vent field
      with B. azoricus showing a great capacity to accumulate metals. The
      bioaccumulation of these metals also varied significantly among tissues. The main
      target was the gills where metals were mainly associated with soluble compounds
      whereas in the digestive gland they were mainly associated with insoluble
      compounds. Storage of metals under insoluble forms in B. azoricus seems to be a
      major pathway for the detoxification of both essential and non-essential metals.
      Mussels from the studied fields can be discriminated following their metallic
      load but the segregation relies partially on the composition of the metal
      enriched fluids.

PMID- 18328555
TI  - The role of loops 3 and 4 in the interdomains and intersubunits communication of
      E. coli cAMP receptor protein.
AB  - Cyclic AMP serves as an intracellular messenger in cells and regulates a variety
      of biological functions by transmitting information through proteins. These
      proteins of different functions all consist of a cAMP-binding motif, and the
      structure of this motif is highly conserved with an exception of the loop 3 and
      4. In current study, cAMP receptor protein was employed as a model system to
      investigate the function of the two loops. The results indicated that the loop 3
      involves in the intersubunits communication of CRP, whereas the loop 4 involves
      in cAMP binding and interdomains communication.

PMID- 18328556
TI  - Introduction of enzymatically degradable poly(trimethylene carbonate)
      microspheres into an injectable calcium phosphate cement.
AB  - Poly(trimethylene carbonate) (PTMC) is an enzymatically degradable polyester with
      rubber-like properties. Introduction of this polymer into an injectable calcium
      phosphate bone cement can therefore be used to introduce macroporosity into the
      cement for tissue engineering purposes as well as to improve mechanical
      properties. Aim of this study was to investigate calcium phosphate cements with
      incorporated PTMC microspheres (PTMC CPCs) on their physical/mechanical
      properties and in vitro degradation characteristics. Therefore, composites were
      tested on setting time and mechanical strength as well as subjected to phosphate
      buffered saline (PBS) and enzyme containing medium. PTMC CPCs (12.5 and 25 wt%)
      with molecular weights of 52.7 kg mol(-1) and 176.2 kg mol(-1) were prepared,
      which showed initial setting times similar to that of original CPC. Though
      compression strength decreased upon incorporation of PTMC microspheres, elastic
      properties were improved as strain-at-yield increased with increasing content of
      microspheres. Sustained degradation of the microspheres inside PTMC CPC occurred
      when incubated in the enzymatic environment, but not in PBS, which resulted in an
      interconnected macroporosity for the 25 wt% composites.

PMID- 18328557
TI  - Maternal asthma and placental morphometry: effects of severity, treatment and
      fetal sex.
AB  - Asthma is the most common respiratory disease to complicate pregnancy. Although
      adverse effects on the fetus have been documented, there is a paucity of
      information regarding the effects of asthma, and its treatment, on placental
      morphology. The aim of this study was to test for volumetric differences in
      placental composition between non-asthmatic pregnancies and those associated with
      maternal asthma grouped according to asthma severity and glucocorticoid (GC)
      treatment. Each placenta was weighed and random samples of tissue were fixed in
      formalin-saline, embedded in wax and analysed by design-based stereology. Volume
      densities of parenchymal compartments (peripheral villi and maternal intervillous
      space) and residual non-parenchyma were estimated by test point counting and
      converted to absolute volumes by taking into account placental size. Relative and
      absolute lengths of villi and capillaries were also estimated and used to derive
      secondary quantities related to villous capillarization and maturation. Between
      group comparisons were drawn by two-way analysis of variance with group and fetal
      sex as the principal factors. Compared to non-asthmatic controls, asthmatics had
      reduced absolute volumes of fetal capillaries which was most marked in those with
      moderate/severe asthma and those using low and high doses of inhaled GCs. Changes
      in the total length and mean cross-sectional area of capillaries and peripheral
      villi were also observed. Lengths were greater in mild asthmatics and lowest in
      those with high GC usage. Calibre areas were lower in mild asthmatics and villous
      calibres in the high GC group were greater than those in asthmatics not taking
      GCs. Those making greatest use of inhaled GCs also had villi which were
      hypovascularized in terms of capillary:villus length ratios. The findings suggest
      that the morphometric differences in fetoplacental vascularity are likely to be
      due to the effects of asthma and use of inhaled GCs rather than the effects of
      maternal or fetal hypoxic stress.

PMID- 18328558
TI  - Calcitonin gene-related peptide release from intact isolated dorsal root and
      trigeminal ganglia.
AB  - Neuropeptides like calcitonin gene-related peptide (CGRP) and substance P are
      found in significant proportions of primary afferent neurons. Release of these
      neuropeptides as well as prostaglandin E(2) is an approved index for the
      activation of these primary afferents. Previous studies have used cultures of
      enzyme-treated and mechanically dissociated primary afferent neurons, fresh
      tissue slices or cubes. In the present study we demonstrate CGRP and
      prostaglandin E(2) release from intact isolated dorsal root and trigeminal
      ganglia. Stimulation with noxious heat, low pH, inflammatory mediators and high
      potassium concentration increased CGRP release. In conclusion, neuropeptide
      release from intact isolated ganglia is a reliable method to study the
      responsiveness of sensory neurons in situ in comparison with neuronal cell
      cultures.

PMID- 18328559
TI  - Fully automated and super-rapid system for the detection of JAK2V617F mutation.
AB  - JAK2V617F is a common mutation in chronic myeloproliferative diseases (CMPDs). We
      have developed a system utilizing JAK2V617F-specific guanine quenching probe (QP
      system) to detect JAK2V617F. With QP-system, results can be obtained from 100
      microl of blood within 90 min. We compared QP-system with direct sequencing using
      42 CMPD patients' specimens. JAK2V617F was detected in 25 specimens by QP-system,
      while direct sequencing failed to detect JAK2V617F in 7 of those 25. The presence
      of JAK2V617F mutation in these 7 specimens was confirmed by allele-specific PCR.
      These findings indicate that QP-system is more sensitive and useful than direct
      sequencing for diagnoses of CMPDs.

PMID- 18328560
TI  - CDKN2A deletions in acute lymphoblastic leukemia of adolescents and young adults:
      an array CGH study.
AB  - Deletion in chromosome 9p involving the CDKN2A locus (9p21.3) is known in many
      malignancies. To detect this deletion in adolescent ALL patients we used oligo
      array CGH and studied 54 patients aged 10-25 years. Deletion rate was 25/54
      (46%), of these 19/25 (76%) were homozygous. Small deletions (<200 kb) were found
      in 8/25 (32%) and the smallest deletion was <30 kb. The only gene affected in all
      deletions was CDKN2A. We were unable to demonstrate prognostic value of the
      deletion, however patients with deletion belonged more often (P=0.06) to
      unfavorable biological category. Our results indicate that CDKN2A deletions <200
      kb may not be detected by conventional methods.

PMID- 18328561
TI  - Effects of four carbamate compounds on antioxidant parameters.
AB  - The effect of four carbamates, aldicarb and its metabolites (aldicarb sulfone and
      aldicarb sulfoxide) and propoxur on glutathione content and the activity of the
      enzymes involved in the sulfur-redox cycle in the mammalian cellular model CHO-K1
      cells after 24-h exposure were determined. Carbamate exposure resulted in a
      depletion of intracellular reduced glutathione (GSH) content, no change was
      observed in oxidized glutathione (GSSG) and a decrease in GSH/GSSG ratio was
      detected. After carbamates exposition a GSH/GSSG decreases in ranged from 12.44%
      to 21.35% of control was observed. Depletion of GSH levels was accompanied by the
      induction of glutathione reductase (GR) after 24h exposure with each of the four
      carbamates to CHO-K1 cells. After aldicarb sulfone, aldicarb sulfoxide, and
      propoxur exposure, glutathione peroxidase (GPx) activity increased in CHO-K1
      cells by 198%, 32%, and 228% of control, respectively. After aldicarb sulfone and
      propoxur exposure, glutathione transferase (GST) activities increased by 49% and
      230% of control, respectively. Due to the role played by GSH in preventing
      cytotoxicity via free-radical scavenging, results obtained suggest that high
      concentrations of aldicarb sulfone and propoxur closely resembling oxidative
      stress in CHO-K1 cells.

PMID- 18328562
TI  - Microcalorimetric measurements of the microbial activities of single- and mixed
      species with trivalent iron in soil.
AB  - A microcalorimetric technique was applied to a series of experiments to follow
      the toxic effect caused by the trivalent iron on the single and mixed microbes in
      sterilized soil that was inoculated with the single Bacillus subtilis (B.
      subtilis) (prokaryotic bacterium), single Candida humicola (C. humicola)
      (eukaryotic fungus) and the mixed-species. The microbial activity was stimulated
      by the addition of 5.0mg glucose and 5.0mg ammonium sulfate under a 35%
      controlled humidity in the studied soil samples of 1.2g. The power-time curves
      from every experiment were analyzed, and from these analyses characteristic
      parameters, such as growth rate constant (k) and total thermal effect (Q) which
      can reflect the biochemical reactions were determined. The mixed-species have
      moderate tolerance to the iron overload, comparing with single species, and
      exhibit synergistic interaction in exponential growth phase (0-400.0 microg mL(
      1)). Meanwhile, there is no much difference in the thermal effect (Q) per gram
      soil sample for the single and mixed culture. This also validates that the
      nutrient substances in natural environment determine the organisms' metabolic
      activities. Ultraviolet-visible spectrophotometry and dissolved oxygen sensor
      also were successfully applied to reflect the activities of B. subtilis and C.
      humicola in the pure culture. The investigation could provide insight into the
      microbial ecology of bacteria and fungi in ecological niches.

PMID- 18328563
TI  - Design of vectors for transgene expression: The use of genomic comparative
      approaches.
AB  - The design of transgenes has always been limited by the extent of available
      information on the endogenous locus whose expression pattern had to be
      replicated. Those genes whose expression domain had not been entirely documented
      resulted, usually, in transgenes with an unpredictable expression patterns and
      suboptimal performance in transgenic animals. The use of genomic comparative
      approaches, highlighting evolutionary conserved homologous DNA sequences, helps
      to identify crucial regulatory elements that are associated to a given expression
      domain. The inclusion of these conserved regulatory sequences in transgenic
      constructs would normally result in optimal expression levels of transgenes in
      recipient animals. The use of artificial chromosome-type transgenes usually
      ensures the inclusion of these preserved regulatory elements that are required
      for the faithful expression of the gene. These constructs could also contain
      insulators, a subset of regulatory sequences whose application is being addressed
      in transgenesis. Therefore, the generation of transgenic animals with genomic
      type constructs is the recommended approach to achieve optimal transgene
      expression, according to the expected pattern of the corresponding endogenous
      locus.

PMID- 18328564
TI  - [Acute stroke imaging before IV thrombolysis: what modality of imaging for France
      in 2007?].
AB  - PURPOSE: To report the results of a radiological survey of the management of
      acute stroke prior to intravenous thrombolysis. MATERIAL AND METHODS: A
      questionnaire on imaging as used in the management of stroke was sent to 80
      stroke units across France at the beginning of 2007 and included the first
      imaging modality used (CT or MRI), the imaging protocol before treatment and the
      exclusion criteria followed for thrombolysis. RESULTS: CT was most often used as
      the first modality for the management of acute stroke (by 70% of the 53
      responding centers) and 26 centers (49%) used both CT and MRI. Only 12 centers
      (22%) routinely performed MRI to screen for acute stroke. However, more than half
      the patients who had received thrombolysis in 2006 had been examined using MRI.
      In fact, after three-hour poststroke, intravenous thrombolysis was predominantly
      decided upon from MRI data. The survey showed that imaging criteria are well
      standardized for CT, whereas they are more variable for MRI. Furthermore, the
      majority (28 of 38) of the centers considered that thrombolysis could be applied
      despite a clinical contraindication (such as unknown time of onset or
      convulsions) if MRI categorically diagnosed an acute stroke. CONCLUSION: This
      survey showed that CT-based screening of acute stroke before thrombolysis remains
      the standard modality in France, with a consensus on decision-making criteria.
      The survey also revealed a change in imaging management, with a growing role for
      MRI as the first examination.

PMID- 18328565
TI  - Domestic science: making chemistry your cup of tea.
AB  - In the early Victorian home, there were plenty of scientific lessons to be
      uncovered. With the appropriate interrogation, everyday objects could transform
      seemingly mundane activities such as eating breakfast, washing clothes or reading
      by candle-light into household lectures that gave children a familiar base from
      which to explore the hidden properties and marvellous histories of common
      commodities. Responding to an unprecedented hunger for scientific knowledge, a
      profusion of introductory texts appeared in the mid-nineteenth century that
      directed lessons into homes across Britain and beyond. In particular, the science
      of chemistry found its way into this domestic setting, as writers promoted its
      practice and practitioners as a source of authoritative expertise on everyday
      life. One of the most compelling illustrations of this encounter between the
      public and chemistry took place over a simple cup of tea.

PMID- 18328566
TI  - A new type of metal-binding site in cobalt- and zinc-containing adenylate kinases
      isolated from sulfate-reducers Desulfovibrio gigas and Desulfovibrio
      desulfuricans ATCC 27774.
AB  - Adenylate kinase (AK) mediates the reversible transfer of phosphate groups
      between the adenylate nucleotides and contributes to the maintenance of their
      constant cellular level, necessary for energy metabolism and nucleic acid
      synthesis. The AK were purified from crude extracts of two sulfate-reducing
      bacteria (SRB), Desulfovibrio (D.) gigas NCIB 9332 and Desulfovibrio
      desulfuricans ATCC 27774, and biochemically and spectroscopically characterised
      in the native and fully cobalt- or zinc-substituted forms. These are the first
      reported adenylate kinases that bind either zinc or cobalt and are related to the
      subgroup of metal-containing AK found, in most cases, in Gram-positive bacteria.
      The electronic absorption spectrum is consistent with tetrahedral coordinated
      cobalt, predominantly via sulfur ligands, and is supported by EPR. The
      involvement of three cysteines in cobalt or zinc coordination was confirmed by
      chemical methods. Extended X-ray absorption fine structure (EXAFS) indicate that
      cobalt or zinc are bound by three cysteine residues and one histidine in the
      metal-binding site of the "LID" domain. The sequence 129Cys-X5-His-X15-Cys-X2-Cys
      of the AK from D. gigas is involved in metal coordination and represents a new
      type of binding motif that differs from other known zinc-binding sites of AK.
      Cobalt and zinc play a structural role in stabilizing the LID domain.

PMID- 18328567
TI  - Treatment-ladder and genetic characterisation of parasites in refractory
      giardiasis after an outbreak in Norway.
AB  - OBJECTIVES: To evaluate the efficacy of a treatment ladder in metronidazole
      refractory giardiasis, and to compare genetic characteristics of the parasites.
      METHODS: A clinical observational study was carried out in 38 adult patients with
      metronidazole-refractory giardiasis, during an outbreak in Norway with more than
      1200 cases. All patients were treated with albendazole in combination with
      metronidazole. Those who failed were treated with paromomycin. Those who failed
      on paromomycin were treated with quinacrine in combination with metronidazole.
      Giardia isolates from 17 patients were characterised by PCR and sequencing at two
      separate genes. RESULTS: Metronidazole in combination with albendazole was
      effective in 30 (79%) out of 38 patients. Paromomycin was effective in three out
      of six patients. Quinacrine in combination with metronidazole was effective in 3
      patients. Molecular characterisation of the Giardia isolates revealed that these
      parasites were identical at two different gene segments, while sequence profiles
      from isolates at the peak of the outbreak were more heterogenous. CONCLUSIONS:
      Albendazole and quinacrine both in combination with metronidazole were effective
      in treating metronidazole-refractory giardiasis in this cohort. Paromomycin was
      less effective. Particular Giardia sub-genotypes may have been associated with
      the treatment-refractory giardiasis in these patients, although other undefined
      factors are probably also of importance.

PMID- 18328568
TI  - suPAR associates to glucose metabolic aberration during glucose stimulation in
      HIV-infected patients on HAART.
AB  - OBJECTIVE: We have recently shown that the level of soluble urokinase plasminogen
      activator receptor (suPAR), which is associated with the immune status of HIV
      infected patients undergoing highly active antiretroviral therapy (HAART),
      correlates with the insulin action of such patients. Here we extend these
      findings by investigating the association of suPAR to glucose metabolic
      insufficiency during an oral glucose challenge (OGTT). METHODS: In 16 HIV
      infected patients with lipodystrophy and 15 HIV-infected patients without
      lipodystrophy, glucose tolerance, insulin sensitivity (ISI(composite)),
      prehepatic insulin secretion, proinsulin level and suppression of free fatty
      acids (FFA) were determined during an OGTT. Stability of suPAR was tested in 6
      HIV-infected patients during a 3h OGTT. RESULTS: Lipodystrophy was associated
      with a 70% increase in plasma suPAR (P<0.05). During the OGTT, plasma suPAR
      correlated inversely with ISI(composite) and positively with 2h plasma glucose,
      fasting insulin secretion, fasting intact proinsulin and FFA level during the
      OGTT (all P<0.05). In multiple regression analyses, in which anthropometric
      measures (BMI, limbadiposity and fat mass), immune markers (CD4, HIV-RNA,
      duration of HIV infection), and dyslipidemia (plasma total cholesterol,
      triglyceride and free fatty acid level during the OGTT) were included, suPAR
      remained a significant marker of glucose tolerance and insulin sensitivity.
      Plasma suPAR exhibited a small CV (11%) during the 3h OGTT. CONCLUSIONS: suPAR
      associated to important glucose metabolic aberrations in HIV-infected patients on
      HAART. Moreover, suPAR was stable after a glucose challenge. Future research is
      required to confirm these findings and explore the potential of suPAR as marker
      of dysmetabolism in HIV-infected patients.

PMID- 18328569
TI  - Septic embolism with subacute onset.

PMID- 18328570
TI  - Automated detection of intercellular signaling in astrocyte networks using the
      converging squares algorithm.
AB  - Intercellular calcium waves in central nervous system astrocyte networks
      underline the principle mechanism of cell signaling in astrocyte syncsytiums,
      which putatively contribute to the modulation of neuronal signaling and metabolic
      regulation. In support of carrying out systems level analyses of astrocyte
      networks, we have optimized and validated the converging squares image
      segmentation algorithm to automatically detect the relative spatial locations of
      all cells in a visible network as a preliminary step towards analyzing the
      dynamics of astrocyte intracellular calcium transients, which are the signals
      that mediate intercellular calcium waves. We used the temporal derivatives of
      pixel intensities as the data source for the algorithm. The method works by
      converging progressively smaller squares until the signal peak is reached. It is
      robust to noise and performs comparably to manual cell signal identification, but
      is much faster and efficient. This is the first reported application of this
      algorithm to glial networks that we are aware of.

PMID- 18328571
TI  - Sharp edge artifacts and spurious coupling in EEG frequency comodulation
      measures.
AB  - Recent electroencephalogram (EEG), electrocorticogram (ECoG), and local field
      potential (LFP) observations suggest that distinct frequency bands interact.
      Numerous measures have been proposed to analyze such interactions, including the
      amplitude envelope modulation of high frequency activity by the phase or signal
      of low frequency activity. In this short communication, we describe how abrupt
      increases or decreases in voltage data may produce spurious coupling in these
      measures and suggest techniques to detect these effects.

PMID- 18328573
TI  - Piezosurgery in the cochleostomy through multiple middle ear approaches.
AB  - OBJECTIVE: Piezosurgery is a new instrument which is able to cut the bone without
      necrosis and non-mineralized tissues damage. The aim of this work has been to
      test Piezosurgery as a new and alternative method in cochleostomy. METHODS: We
      have performed Piezosurgery on nine temporal bone specimens from voluntary bone
      donors. Piezosurgery was used in the mastoidectomy with posterior tympanotomy
      approach (three specimens), suprameatal approach (three specimens) and combined
      approach (three specimens). The piezoelectric device uses low frequency
      ultrasonic waves (24.7-29.5 kHz), the applied power can be modulated between 2.8
      and 16 W, and is programmed in accordance to the density of the bone. The
      equipment consists of two handpieces, two inserts and two peristaltic pumps: the
      microvibrations that are created in the piezoelectric handpiece cause the inserts
      to vibrate linearly between 60 and 210 microm. RESULTS: In all the specimens,
      Piezosurgery provided excellent control without side effects on the adjacent
      structures of the middle and inner ear. CONCLUSIONS: Piezosurgery is a new and
      revolutionary osteotomy technique utilizing the microvibrations of scalpels at
      ultrasonic frequency, so that soft tissue will not be damaged even upon
      accidental contact with the cutting tip. The vibration frequency of Piezosurgery
      is optimal for mineralized tissue and does not cut the adjacent soft tissue,
      minimizing the risk of harming the adjacent tissues: this renders the
      piezoelectric device ideal for cochlear implantation in children with ossified,
      partial ossified cochlea and/or malformation of ear.

PMID- 18328572
TI  - Effects of estrogen receptor agonists on regulation of the inflammatory response
      in astrocytes from young adult and middle-aged female rats.
AB  - Estrogen has been shown to attenuate the inflammatory response following injury
      or lipopolysaccharide treatment in several organ systems. Estrogen's actions are
      transduced through two estrogen receptor sub-types, estrogen receptor (ER) -alpha
      and estrogen receptor-beta, whose actions may be overlapping or independent of
      each other. The present study examined the effects of ERalpha- and ERbeta
      specific ligands in regulating the inflammatory response in primary astrocyte
      cultures. Pre-treatment with 17beta-estradiol (ERalpha/ERbeta agonist), HPTE
      (ERalpha agonist/ERbeta antagonist) and DPN (ERbeta agonist) led to attenuation
      of IL-1beta, TNFalpha, and MMP-9 in astrocyte media derived from young adult (3-4
      mos.) and reproductive senescent female (9-11 mos., acyclic) astrocyte cultures,
      while pretreatment with PPT (ERalpha agonist) attenuated IL-1beta (but not MMP-9)
      in both young and senescent-derived astrocyte cultures. Our previous work
      determined that 17beta-estradiol was unable to attenuate the LPS-induced increase
      in IL-1beta in olfactory bulb primary microglial cultures derived from either
      young adult or reproductive senescent females. In young adult-derived microglial
      cultures, the LPS-induced increase in IL-1beta was not attenuated by pre
      treatment with 17beta-estradiol, PPT or HPTE. Interestingly, the ERbeta agonist,
      DPN significantly decreased IL-1beta following LPS treatment in young adult
      derived microglia. Thus while both microglia and astrocytes synthesize and
      release inflammatory mediators, the present data shows that compounds which bind
      ERbeta are more effective in attenuating proinflammatory cytokines in both cell
      types and may therefore be a more effective agent for future therapeutic use.

PMID- 18328574
TI  - Prevalence of adenoid hypertrophy and nocturnal enuresis in primary school
      children in Istanbul, Turkey.
AB  - OBJECTIVE: The purpose of this study is to investigate the prevalence of an
      existing relationship between adenoid hypertrophy and nocturnal enuresis in
      primary school children. METHODS: The study was performed in four primary schools
      that were chosen randomly in Kartal, Istanbul. The children's parents were asked
      to fill out a questionnaire that included questions concerning the associated
      symptoms of adenoid hypertrophy and nocturnal enuresis. The interrelations
      between adenoid hypertrophy and nocturnal enuresis items were examined by X2
      tests. RESULTS: The study population consisted of 1132 (625 girls, 621 boys)
      primary school children between 5 and 14 years of age (mean 9.59+/-2.60 years).
      The children were divided into three groups with 5-7 years old children in Group
      I (n=232), 8-10 years old children in Group II (n=506) and 11-14 years old
      children in Group III (n=394). Of the 1132 distributed questionnaires, 1090
      (87.4%) were filled in adequately and were accepted for evaluation. Prevalence of
      adenoid hypertrophy in school children was found to be 58 in Group I (27%), 94 in
      Group II (19.5%) and 78 in Group III (19.9%). Prevalence of nocturnal enuresis in
      school children was found to be 35 in Group I (15.1%), 51 in Group II (10.1%) and
      18 in Group III (4.6%). No statistically significant association was present
      between adenoid hypertrophy and nocturnal enuresis in either Group I, II or III
      school children. CONCLUSION: In contrast to previous studies, our prevalence
      study did not find an association between adenoid hypertrophy and nocturnal
      enuresis. Thus, this prevalence study provides otolaryngologists new and
      interesting information.

PMID- 18328575
TI  - Detection of high-risk human papillomavirus by two molecular techniques: hybrid
      capture and linear array.
AB  - A number of human papillomaviruses (HPV) are the etiological agents of cervical
      cancer. The present study compared the performance of the hybrid capture method
      with that of linear array for the detection of high-risk HPV in 218 cervical
      samples. For the linear array technique, the DNA was extracted using two
      different procedures, one manual and the other automated. There was no difference
      in high-risk HPV (HR-HPV) detectability between the two extraction procedures but
      the automated procedure had the advantages of simplicity, time and efficiency.
      There was agreement in 199 (91.3%) of the results. The K value for the two assays
      was 0.81 indicative of "near perfect" agreement. Both methods, hybrid capture and
      linear array, are sensitive options for detection of HPV in cervical samples.
      Linear array enables the identification of the genotype present in the sample and
      the presence of multiple infections.

PMID- 18328576
TI  - Single-step RT real-time PCR for sensitive detection and discrimination of Potato
      virus Y isolates.
AB  - Potato virus Y (PVY) has a worldwide distribution and infects several
      economically important crops from the Solanaceae family. The emergence and spread
      of the PVYNTN strain, which is the causative agent of potato tuber necrotic
      ringspot disease (PTNRD), has lead to large economic losses and highlighted the
      need for accurate discrimination of the different PVY strains. Detection and
      differentiation of PVY isolates is mainly based on a combination of ELISA, RT-PCR
      and bioassays; however, PVYNTN isolates are particularly difficult to
      differentiate from standard PVYN without the use of time-consuming bioassays. A
      strong correlation has been identified previously between the ability to induce
      PTNRD and the presence of a recombination point in the virus coat protein. An RT
      real-time PCR assay has been developed to enable detection of isolates with the
      recombination point, therefore, enabling rapid differentiation between
      potentially tuber necrotic PVYNTN isolates and standard PVYN isolates. The assay
      is also able to detect the presence of PVYO isolates. To aid with routine
      testing, immuno-capture and post-ELISA virus release were introduced; when
      coupled with RT real-time PCR the sensitivity of the assays were up to seven
      orders of magnitude higher than ELISA. The assay was shown to be a suitable
      method for rapid large-scale diagnostic testing of PVY in different types of
      plant material including tubers, and specific screening for potentially tuber
      necrotic recombinant isolates.

PMID- 18328577
TI  - Do all animals sleep?
AB  - Some animals never exhibit a state that meets the behavioral definition of sleep.
      Others suspend or greatly reduce 'sleep' behavior for many weeks during the
      postpartum period or during seasonal migrations without any consequent 'sleep
      debt.' Rats die from one form of sleep deprivation, but sleep loss has not been
      shown to cause death in well-controlled studies in other vertebrate species. Some
      marine mammal species do not show evidence for REM sleep, and convincing evidence
      for this state in reptiles, fish and insects is lacking. The enormous variation
      in the nature of rest and sleep states across the animal kingdom and within the
      mammalian class has important implications for understanding the evolution and
      functions of sleep.

PMID- 18328579
TI  - Maternal pinealectomy increases depressive-like responses in Siberian hamster
      offspring.
AB  - This study investigated the effect of maternal pinealectomy and postnatal
      pinealectomy on affective responses. Siberian hamsters were born to either
      pinealectomized or sham-operated dams and then underwent pinealectomy or a sham
      operation. Maternal pinealectomy increased depressive-like responses of offspring
      in the forced swim test. Maternal pinealectomy increased rearing behaviour and
      postnatal pinealectomy increased locomotor behaviour in the open field test.
      These results suggest that prenatal melatonin organizes adult affective
      responses.

PMID- 18328578
TI  - Current and future antiviral therapy of severe seasonal and avian influenza.
AB  - The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a
      transient, febrile upper respiratory illness in most adults and children
      ("seasonal influenza"), but infants, the elderly, immunodeficient and chronically
      ill persons may develop life-threatening primary viral pneumonia or complications
      such as bacterial pneumonia. By contrast, avian influenza viruses such as the
      H5N1 virus that recently emerged in Southeast Asia can cause severe disease when
      transferred from domestic poultry to previously healthy people ("avian
      influenza"). Most H5N1 patients present with fever, cough and shortness of breath
      that progress rapidly to adult respiratory distress syndrome. In seasonal
      influenza, viral replication remains confined to the respiratory tract, but
      limited studies indicate that H5N1 infections are characterized by systemic viral
      dissemination, high cytokine levels and multiorgan failure. Gastrointestinal
      infection and encephalitis also occur. The licensed anti-influenza drugs (the M2
      ion channel blockers, amantadine and rimantadine, and the neuraminidase
      inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal
      influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral
      infections have not been defined. Treatment options may be limited by the rapid
      emergence of drug-resistant viruses. Ribavirin has also been used to a limited
      extent to treat influenza. This article reviews licensed drugs and treatments
      under development, including high-dose oseltamivir; parenterally administered
      neuraminidase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir;
      the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent
      and monoclonal antibodies; and combination therapies.

PMID- 18328580
TI  - Hemiparkinsonian rats rotate toward the side with the weaker dopaminergic
      neurotransmission.
AB  - Rats with unilateral lesion of the substantia nigra pars compacta (SNpc) have
      been used as a model of Parkinson's disease. Depending on the lesion protocol and
      on the drug challenge, these rats rotate in opposite directions. The aim of the
      present study was to propose a model to explain how critical factors determine
      the direction of these turns. Unilateral lesion of the SNpc was induced with 6
      hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
      Separate analysis showed that neither the type of neurotoxin nor the site of
      lesion along the nigrostriatal pathway was able to predict the direction of the
      turns these rats made after they were challenged with apomorphine. However, the
      combination of these two factors determined the magnitude of the lesion estimated
      by tyrosine-hydroxylase immunohistochemistry and HPLC-ED measurement of striatal
      dopamine. Very small lesions did not cause turns, medium-size lesions caused
      ipsiversive turns, and large lesions caused contraversive turns. Large-size SNpc
      lesions resulted in an increased binding of [(3)H]raclopride to D2 receptors,
      while medium-size lesions reduced the binding of [(3)H]SCH-23390 D1 receptors in
      the ipsilateral striatum. These results are coherent with the model proposing
      that after challenged with a dopamine receptor agonist, unilaterally SNpc
      lesioned rats rotate toward the side with the weaker activation of dopamine
      receptors. This activation is weaker on the lesioned side in animals with small
      SNpc lesions due to the loss of dopamine, but stronger in animals with large
      lesions due to dopamine receptor supersensitivity.

PMID- 18328581
TI  - Modelling foot-and-mouth disease: a comparison between the UK and Denmark.
AB  - Whilst the UK 2001 FMD (foot-and-mouth disease) outbreak provides an extremely
      rich source of spatio-temporal epidemic data, it is not clear how the models and
      parameters from the UK can be translated to other scenarios. Here we consider how
      the model framework used to capture the UK epidemic can be applied to a
      hypothetical FMD outbreak in Denmark. Whilst pigs played a relatively minor role
      in the UK epidemic (being the infected animal on just 18 farms), they dominate
      the Danish livestock landscape. In addition, it is not clear whether transmission
      parameters from the UK will transfer to Denmark where farming practices may be
      significantly different. We therefore explore a large volume of high-dimensional
      parameter space, but seek to relate final epidemic size, risk of spread to Danish
      islands and potential success of control measures, to early indicators of
      epidemic dynamics. The results of this extensive modelling exercise therefore
      allow us to provide timely advice on control options based on the observed
      behaviours of the first few generations.

PMID- 18328582
TI  - A simple whole cell based high throughput screening protocol using Mycobacterium
      bovis BCG for inhibitors against dormant and active tubercle bacilli.
AB  - This study aimed at developing a whole cell based high throughput screening
      protocol to identify inhibitors against both active and dormant tubercle bacilli.
      A respiratory type of nitrate reductase (NarGHJI), which was induced during
      dormancy, could reflect the viability of dormant bacilli of Mycobacterium bovis
      BCG in microplate adopted model of in vitro dormancy. Correlation between
      reduction in viability and nitrate reductase activity was seen clearly when
      dormant stage inhibitor metronidazole and itaconic anhydride were applied in this
      in vitro microplate model. Active replicating stage could also be monitored in
      the same assay by measuring the A(620) of the culture. MIC values of 0.08, 0.075,
      0.3 and 3.0 microg/ml, determined through monitoring A(620) in this assay for
      rifampin, isoniazid, streptomycin and ethambutol respectively, were well in
      agreement with previously reported by BACTEC and Bio-Siv assays. S/N ratio and Z'
      factor for the assay were 8.5 and 0.81 respectively which indicated the
      robustness of the protocol. Altogether the assay provides an easy, inexpensive,
      rapid, robust and high content screening tool to search novel antitubercular
      molecules against both active and dormant bacilli.

PMID- 18328583
TI  - The effect of probiotics and organic acids on Shiga-toxin 2 gene expression in
      enterohemorrhagic Escherichia coli O157:H7.
AB  - Probiotics are known to have an inhibitory effect against the growth of various
      foodborne pathogens, however, the specific role of probiotics in Shiga-toxin
      producing Escherichia coli (STEC) virulence gene expression has not been well
      defined. Shiga toxins are members of a family of highly potent bacterial toxins
      and are the main virulence marker for STEC. Shiga toxins inhibit protein
      synthesis in eukaryotic cells and play a role in hemorrhagic colitis and
      hemolytic uremic syndrome. STEC possesses Shiga toxin 1 (Stx1) and Shiga toxin 2
      (Stx2), both of which have A and B subunits. Although STEC containing both Stx1
      and Stx2 has been isolated from patients with hemorrhagic colitis, Stx2 is more
      frequently associated with human disease complications. Thus, the effect of
      Lactobacillus, Pediococcus, and Bifidobacterium strains on stx2A expression
      levels in STEC was investigated. Lactic acid bacteria and bifidobacteria were
      isolated from farm animals, dairy, and human sources and included L. rhamnosus
      GG, L. curvatus, L. plantarum, L. jensenii, L. acidophilus, L. casei, L. reuteri,
      P. acidilactici, P. cerevisiae, P. pentosaceus, B. thermophilum, B. boum, B. suis
      and B. animalis. E. coli O157:H7 (EDL 933) was coincubated with sub-lethal
      concentrations of each probiotic strain. Following RNA extraction and cDNA
      synthesis, relative stx2A mRNA levels were determined according to a comparative
      critical threshold (Ct) real-time PCR. Data were normalized to the endogenous
      control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the level of stx2A
      expression between treated and untreated STEC was compared. Observed for all
      probiotic strains tested, stx2A was down-regulated, when compared to the control
      culture. Probiotic production of organic acids, as demonstrated by a decrease in
      pH, influenced stx2A gene expression.

PMID- 18328584
TI  - Correlation of intra-tumour heterogeneity on 18F-FDG PET with pathologic features
      in non-small cell lung cancer: a feasibility study.
AB  - We evaluated the feasibility to correlate intra-tumour heterogeneity as
      visualized on 18F-FDG PET with histology for NSCLC. For this purpose we used an
      ex-vivo model. The procedure was feasible in all operated patients. We have shown
      that this method is suitable for correlating intra-tumour heterogeneity in tracer
      uptake with histology.

PMID- 18328585
TI  - Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine
      during head and neck radiotherapy.
AB  - Amifostine is an organic thiophosphate prodrug used for cytoprotection against
      toxic effects of radiotherapy and chemotherapy. In a European prospective study
      of SJS/TEN, six patients were suspected to have SJS/TEN associated with
      amifostine. Our findings suggest that the risk of life-threatening cutaneous
      adverse reactions to amifostine could be significantly increased.

PMID- 18328586
TI  - MEG in paediatrics: introduction to the special issue.

PMID- 18328587
TI  - Effect of storage in juice with or without pulp and/or calcium lactate on the
      subsequent survival of Escherichia coli O157:H7 in simulated gastric fluid.
AB  - A study was conducted to evaluate the effect of storing Escherichia coli O157:H7
      in fruit or vegetable juices with or without pulp and/or calcium lactate, on the
      bacterial resistance to a simulated gastric fluid (SGF, pH 1.5). Apple, carrot,
      orange, and tomato juices containing pulp or freed from pulp by filtration were
      used in this study. Calcium lactate at about 1.4 g/l was added to juices to
      obtain calcium supplemented juices. Juices with or without pulp and/or calcium
      lactate were inoculated with E. coli O157:H7 and then were stored at 7 degrees C
      for 0, 1, 2, or 4 days. The acid resistance of cells stored in juices with or
      without pulp and/or calcium lactate was determined by incubating in SGF for 90 or
      240 min at 37 degrees C. Cells stored in apple juice for 4 days, carrot juice for
      2 days, and orange juice for 4 days with pulp only had greater acid resistance,
      while all cells stored in tomato juice with pulp had greater acid resistance than
      cells stored in juice without pulp. The D-values of cells stored in supplemented
      apple and orange juices with calcium lactate declined 1.7-3.5 fold, whereas D
      values of cells stored in supplemented tomato juice decreased by about 1.4-fold
      when compared to cells stored in juice without calcium lactate after exposure in
      SGF. These results indicate that storing E. coli O157:H7 in juices with pulp had
      little or no effect on the acid resistance of cells during subsequent exposure in
      SGF. Calcium lactate supplemented into juices could dramatically decrease the
      ability of E. coli O157:H7 to survive in SGF, possibly reducing the risk of
      foodborne illness by juice products.

PMID- 18328588
TI  - Production of an infectious Herpesvirus saimiri-based episomally maintained
      amplicon system.
AB  - Viral vectors have a number of obstacles to overcome for effective gene therapy,
      including immune stimulation, packaging potential and cell tropism. Herpesvirus
      saimiri (HVS) has many favourable traits including, a large packaging capability,
      wide cell tropism, and the ability to episomally persist as an artificial
      chromosome. To further develop HVS as a gene therapy vector we aim to produce a
      safe disabled HVS-based recombinant viral system for gene therapy applications.
      An HVS recombinant viral amplicon was constructed with a transgene packaging
      potential of 50 kb. The recombinant HVS genome was shown to be replication
      disabled and used to generate a stable cell line, OMKHVS Delta Bam, in which the
      modified genome persists as a non-integrated episome. To assess whether the
      modified genome could be packaged into a virus-like particle (HVSampVLP), OMKHVS
      Delta Bam was infected with replication competent virus or transfected with a
      defective helper virus. The resultant HVSampVLPs were able to infect SW480 tumour
      cells, delivering the recombinant disabled genome, which persisted as a non
      integrated episome in the dividing cell population. This study forms the basis of
      a replication disabled HVS amplicon system for use in gene therapy applications.

PMID- 18328589
TI  - Comparison of coronary flow velocity reserve and aortic distensibility in
      diabetic versus non-diabetic patients with and without aortic atherosclerosis.
AB  - Coronary flow velocity reserve (CFR) and aortic distensibility are altered both
      in diabetes and in the presence of aortic atherosclerosis (AA). Transoesophageal
      echocardiography has been demonstrated to be a suitable method for simultaneous
      evaluation of these functional parameters. In the present study no significant
      difference could be observed in CFR and aortic distensibility in diabetic
      patients compared to non-diabetic subjects with or without AA.

PMID- 18328590
TI  - Contrast-enhanced ultrasound in the diagnosis of hepatocellular carcinoma.
AB  - Surveillance of patients at risk of developing hepatocellular carcinoma (HCC) is
      based on ultrasound (US) examinations performed at either 6 or 12 month
      intervals. Early detection of HCC in patients with cirrhosis is a challenging
      issue, since the different entities that are involved in the multi-step process
      of hepatocarcinogenesis--such as low-grade and high-grade dysplastic nodule-
      share common US features. Contrast-enhanced US allows reliable detection of
      arterial neoangiogenesis associated with a malignant transformation. Several
      reports have shown that the ability of contrast-enhanced US to diagnose HCC
      currently approaches that of optimized multidetector computed tomography (CT) or
      dynamic magnetic resonance (MR) imaging protocols. The use of contrast-enhanced
      US to characterize nodular lesions in cirrhosis has been recently recommended by
      the clinical practice guidelines issued by the European Federation of Societies
      for Ultrasound in Medicine and Biology and the American Association for the Study
      of Liver Diseases. However, contrast-enhanced US has not resulted in any
      significant improvement in the ability of US to detect small tumor foci, since a
      comprehensive assessment of the whole liver parenchyma cannot be accomplished
      during the short duration of the arterial phase. Hence, CT or MR imaging are
      still mandatory for proper intrahepatic staging of the disease.

PMID- 18328591
TI  - Loss of progranulin function in frontotemporal lobar degeneration.
AB  - Frontotemporal lobar degeneration (FTLD) represents a collection of
      neurodegenerative diseases of frontal and temporal brain regions. It has long
      been associated with mutations in microtubule-associated protein tau (MAPT), and
      more recently with loss-of-function mutations in progranulin (PGRN). Phenotypes
      of PGRN and MAPT mutation carriers overlap, although disease onset in PGRN
      carriers is a decade later. Mutations in PGRN might influence susceptibility to a
      wider range of neurodegenerative diseases including Alzheimer and Parkinson
      diseases. The recent demonstration that mutations in PGRN result in FTLD provided
      a novel entrance point to the molecular mechanisms leading to this disorder. The
      high variability in onset age and age-dependent penetrance suggests that the PGRN
      pathway is highly susceptible to modulating factors that might be exploited to
      delay the disease processes.

PMID- 18328592
TI  - Protons extruded by NHE1: digestive or glue?
AB  - Many physiological and pathophysiological processes, such as embryogenesis,
      immune defense, wound healing, or metastasis, are based on cell migration and
      invasion. The activity of the ubiquitously expressed NHE1 isoform of the plasma
      membrane Na(+)/H(+) exchanger is one of the requirements for directed locomotion
      of migrating cells. The mechanisms by which NHE1 is involved in cell migration
      are multiple. NHE1 contributes to cell migration by affecting the cell volume, by
      regulating the intracellular pH and thereby the assembly and activity of
      cytoskeletal elements, by anchoring the cytoskeleton to the plasma membrane, by
      the organization of signal transduction and by regulating gene expression. The
      present review focuses on two additional, extracellular mechanisms by which NHE1
      activity contributes to cell migration and invasion. Protons extruded by the NHE1
      lead to local, extracellular acidification which, on the one hand, can create pH
      optima needed for the activity of proteinases at invadopodia/podosomes necessary
      for extracellular matrix digestion and, on the other hand, facilitates
      cell/matrix interaction and adhesion at the cell front.

PMID- 18328593
TI  - In contrast to the nematode and fruit fly all 9 intron positions of the sea
      anemone lamin gene are conserved in human lamin genes.
AB  - We identified the single gene for nuclear lamin in the genome draft of the sea
      anemone Nematostella vectensis, a member of the cnidaria, a very old metazoan
      phylum. The gene consists of 10 exons and 9 introns. Strikingly all 9 intron
      positions are conserved in the human lamin B genes, which have only 1 (lamin B1)
      or 2 (lamin B2) additional introns. Using the information on neighboring genes we
      propose that the human lamin B1 gene on chromosome 5 is the true homolog of the
      Nematostella lamin gene, while the lamin B2 gene on chromosome 19 arose during
      vertebrate evolution. In marked contrast to this conservation of gene structure
      are the results in the rapidly evolving genomes of Drosophila and Caenorhabditis
      elegans. Here the lamin genes have much fewer introns and these occur often at
      novel positions. In the single nematode lamin gene and the Drosophila lamin Dmo
      gene no intron position coincides with an intron in the sea anemone lamin gene.

PMID- 18328594
TI  - Prevalence and correlates of indoor tanning among US adults.
AB  - BACKGROUND: Little is known about the prevalence of indoor tanning among the US
      general adult population. OBJECTIVES: This study sought to: (1) describe the
      prevalence of indoor tanning throughout adulthood; (2) identify demographic and
      psychosocial correlates of indoor tanning; and (3) determine whether these
      correlates vary by age group. METHODS: This study used data from the 2005
      National Health Interview Survey, an annual health survey of the US adult
      population. RESULTS: Indoor tanning rates were higher among individuals who were
      young, white, and female. Rates of indoor tanning in the last year varied from
      20.4% for those aged 18 to 29 years to 7.8% for those aged 65 years and older. A
      variety of demographic, health, and behavioral health risk factors correlated
      with indoor tanning. LIMITATIONS: The study design was cross-sectional and all
      data were self-reported. CONCLUSIONS: Health care providers should address indoor
      tanning as a health risk factor across the lifespan.

PMID- 18328595
TI  - Cutaneous Mycobacterium haemophilum infection in iatrogenically immunocompromised
      patients without transplantation.
AB  - Cutaneous Mycobacterium haemophilum infections are most often the result of HIV
      or transplantation-associated immunosuppression. Rarely, M. haemophilum may
      infect healthy patients or iatrogenically immunosuppressed patients without
      transplantation. We herein report two cases of cutaneous M. haemophilum infection
      in HIV-negative patients without transplantation undergoing iatrogenic
      immunosuppression. Our cases and a literature review highlight the various
      clinical contexts in which M. haemophilum may arise in this patient population.
      Accordingly, we emphasize that a high index of suspicion is needed for diagnosis,
      which ultimately relies on skin biopsy, histopathologic examination, and culture.

PMID- 18328596
TI  - Melanoma mimicking seborrheic keratosis: an error of perception precluding
      correct dermoscopic diagnosis.
AB  - Seborrheic keratosis is a common skin lesion that can usually be recognized
      either clinically or dermoscopically. However, melanomas mimicking seborrheic
      keratoses, as well as melanomas arising in association with seborrheic keratoses,
      have been described. We report the case of a patient with a lesion that initially
      revealed "classic" dermoscopic features of a seborrheic keratosis. However,
      during follow-up, changes in color developed within the center of the lesion that
      led the clinician to the correct diagnosis of melanoma. Upon retrospective
      evaluation of the baseline image of the lesion; the clinician was now able to
      "see" that which his brain could not appreciate on initial examination and to
      realize that the lesion had subtle features suspect for melanoma. This case
      represents a diagnostic pitfall due to errors in perception. Dermatologists
      should be cognizant of "errors in perception"; we suggest that a final
      dermoscopic judgment of a seborrheic keratosis be rendered by combining the
      gestalt diagnosis of the overall pattern, with deliberate dermoscopic analysis of
      all quadrants of the lesion.

PMID- 18328597
TI  - Delayed autoimmune hemolytic anemia in efalizumab-treated psoriasis.
AB  - Efalizumab, a humanized anti-CD11a monoclonal antibody, has been shown to treat
      plaque psoriasis. A known association between this drug and autoimmune
      thrombocytopenia has already been established. More recently publicized, however,
      is efalizumab's ability to affect another cell line--that of the erythrocyte--and
      cause an autoimmune hemolytic anemia that typically occurs 4 to 6 months after
      initiating therapy. In this article, we report the case of a patient who
      developed autoimmune hemolytic anemia after 8 months of successful treatment with
      efalizumab. His delayed presentation suggests that monitoring of blood cell
      counts longer than 6 months may be warranted.

PMID- 18328598
TI  - Quantitative assessment of diagnostic radiation doses in adult blunt trauma
      patients.
AB  - STUDY OBJECTIVE: Many emergency departments and trauma centers utilize extensive
      radiologic studies during the assessment of trauma patients. A point of concern
      arises about the possible biological effects of these cumulative radiation doses.
      The objective of this study is to determine the amount of ionizing radiation
      received by adult blunt trauma patients at a Level I trauma center during the
      first 24 hours of their care. METHODS: This nonconcurrent case series reviewed
      the first 100 consecutive adult blunt trauma patients who presented to a Level I
      trauma center in 2006. All patients met hospital standards for the less acute
      major triage criteria. Individual radiation dose reports calculated by the
      computed tomography (CT) scanner were used to determine the radiation doses from
      each CT procedure. Standardized tables were used to determine radiation dose for
      plain radiographs. The median effective dose of radiation (millisieverts) was
      calculated for the first 24 hours of hospitalization. RESULTS: A total of 100
      eligible patients presented between January 1, 2006, and March 20, 2006. Eighty
      six patients had complete radiologic records available. The median age was 32
      years, with an intraquartile range of 23 to 46 years; the median Injury Severity
      Score was 14, with an intraquartile range of 9 to 29; and the median number of CT
      scans was 3, with an intraquartile range of 3 to 4. The median effective total
      dose of ionized radiation was 40.2 mSv, with an intraquartile range of 30.5 to
      47.2 mSv. A dose of 40.2 mSv is the equivalent of approximately 1,005 chest
      radiographs. CONCLUSION: Trauma patients meeting the less acute major triage
      criteria are exposed to clinically important radiation doses from diagnostic
      radiographic imaging during the first 24 hours of their care.

PMID- 18328599
TI  - Antitumor effects, cell selectivity and structure-activity relationship of a
      novel antimicrobial peptide polybia-MPI.
AB  - A novel antimicrobial peptide, polybia-MPI, was purified from the venom of the
      social wasp Polybia paulista. It has potent antimicrobial activity against both
      Gram-positive and Gram-negative bacteria, but causing no hemolysis to rat
      erythrocytes. To date, there is no report about its antitumor effects on any
      tumor cell lines. In this study we synthesized polybia-MPI and studied its
      antitumor efficacy and cell selectivity. Our results revealed that polybia-MPI
      exerts cytotoxic and antiproliferative efficacy by pore formation. It can
      selectively inhibit the proliferation of prostate and bladder cancer cells, but
      has lower cytotoxicity to normal murine fibroblasts. In addition, to investigate
      the structure-activity relationship of polybia-MPI, three analogs in which Leu7,
      Ala8 or Asp9 replaced by L-Pro were designed and synthesized. L-Pro substitution
      of Leu7 or Asp9 significantly reduces the content of alpha-helix conformation,
      and L-Pro substitution of Ala8 can disrupt the alpha-helix conformation
      thoroughly. The L-Pro substitution induces a significant reduction of antitumor
      activity, indicating that the alpha-helix conformation of polybia-MPI is
      important for its antitumor activity. In summary, polybia-MPI may offer a novel
      therapeutic strategy in the treatment of prostate cancer and bladder cancer,
      considering its relatively lower cytotoxicity to normal cells.

PMID- 18328600
TI  - Alterations in kynurenine precursor and product levels in schizophrenia and
      bipolar disorder.
AB  - Increased concentrations of kynurenine pathway metabolites have been reported by
      several groups for disorders involving psychosis, including schizophrenia and
      bipolar disorder. To identify components of the pathway that may be relevant as
      biomarkers or may underlie the etiology of psychosis, it is essential to
      characterize the extent of kynurenine pathway activation and to investigate known
      regulators of one of the key kynurenine-producing enzymes, tryptophan 2,3
      dioxygenase (TDO2), previously shown in this laboratory to be increased
      commensurate with kynurenine in postmortem anterior cingulate brain tissue from
      individuals with schizophrenia. Using this same anterior cingulate sample set
      from individuals with schizophrenia, bipolar disorder, depression and controls
      (N=12-14 per group), we measured the precursor of kynurenine and two downstream
      products. The precursor, tryptophan, was significantly increased only in the
      schizophrenia group (1.54-fold the mean control value, p=0.02), and through
      substrate-induced activation, may be one cause of the increased kynurenine and
      kynurenine metabolites. This finding for tryptophan differs from some, but not
      all, previous reports and methodological reasons for the discrepancies are
      discussed. A product of kynurenine metabolism, 3-OH-anthranilic acid was also
      significantly increased only in the schizophrenia group (1.68-fold the mean
      control value, p=0.03). 3-OH-anthranilic acid is a reactive species with
      cytotoxic properties, although the threshold for such effects is not known for
      neurons. Analysis of major pre- and post-mortem variables showed that none were
      confounding for these between-group experimental comparisons. Nicotinamide, a
      pathway end product, did not differ between groups but was associated with cause
      of death (suicide) within the bipolar group (p=0.03).

PMID- 18328601
TI  - Effects of Amphotericin B on the expression of neurotoxic and neurotrophic
      factors in cultured microglia.
AB  - Amphotericin B (AmB) is a polyene antibiotic and reported to have therapeutic
      effects on prion diseases, in which the microglial activation has been suggested
      to play important roles by proliferating and producing various factors such as
      nitric oxide, proinflammatory cytokines, and so on. However, the therapeutic
      mechanism of AmB on prion diseases remains elusive. In the present study, we
      investigated the effects of AmB on cellular functions of rat primary cultured
      microglia. We found that AmB, similarly as lipopolysaccharide (LPS), could
      activate microglia to produce nitric oxide via inducible nitric oxide synthase.
      Both AmB and LPS also induced mRNA expressions of interleukin-1beta, interleukin
      6, and tumor necrosis factor-alpha in microglia. AmB also changed the expression
      levels of neurotrophic factors mRNAs. AmB and LPS significantly down-regulated
      the level of ciliary neurotrophic factor mRNA. However, AmB, but not LPS,
      significantly up-regulated the level of glial cell-line derived neurotrophic
      factor mRNA in microglia. In addition, brain-derived neurotrophic factor mRNA
      expression level was tending upward by treatment with AmB, but not with LPS.
      Taken together, these results suggest that AmB regulates the microglial
      activation in different manner from LPS and that microglia may participate in the
      therapeutic effects of AmB on prion diseases by controlling the expression and
      production of such mediators.

PMID- 18328602
TI  - 14-3-3 CSF levels in sporadic Creutzfeldt-Jakob disease differ across molecular
      subtypes.
AB  - BACKGROUND: The 14-3-3 protein is a physiological cellular protein expressed in
      various tissues, and its release to CSF reflects extensive neuronal damage as in
      Creutzfeldt-Jakob disease (CJD), but also in other neurological diseases. 14-3-3
      protein in CSF in the proper clinical context is a reliable diagnostic tool for
      sporadic CJD. However, the sensitivity varies across molecular CJD subtypes.
      OBJECTIVE: We determined the level of the 14-3-3 protein in CSF from 70 sporadic
      CJD patients with distinct molecular subtypes using an improved enzyme-linked
      immunosorbent assay (ELISA) protocol technique. RESULTS: The 14-3-3 levels varied
      markedly across various molecular subtypes. The most elevated levels of 14-3-3
      protein were observed in the frequently occurring and classical subtypes, whereas
      the levels were significantly lower in the subtypes with long disease duration
      and atypical clinical presentation. PRNP codon 129 genotype, PrP(sc) isotype,
      disease stage and clinical subtype influenced the 14-3-3 level and the test
      sensitivity. CONCLUSIONS: The 14-3-3 protein levels differ across molecular
      subtypes and might be used for their early pre-mortem identification when the
      codon 129 genotype is known, especially for the less common molecular subtypes
      such as MV2 and MM2.

PMID- 18328603
TI  - Synthesis, anti-tubercular activity and 3D-QSAR study of coumarin-4-acetic acid
      benzylidene hydrazides.
AB  - A set of 25 coumarin-4-acetic acid benzylidene hydrazides were synthesized and
      characterized by NMR, IR and mass spectroscopic techniques. The compounds were
      evaluated for their anti-tubercular activity against Mycobacterium tuberculosis
      H(37)Rv strain using the BACTEC 460 system to determine percentage inhibition. To
      understand the relationship between structure and activity, a 3D-QSAR analysis
      has been carried out by Comparative Molecular Field Analysis (CoMFA). Several
      statistically significant CoMFA models were generated. The CoMFA model generated
      with database alignment was the best in terms of overall statistics. The CoMFA
      contours provide a good insight into the structure activity relationships of the
      compounds reported herein.

PMID- 18328604
TI  - [Tobacco reduction in a prison of France].
AB  - SUBJECT: Little is known about free nicotine transdermal patch efficacy on
      tobacco reduction in prisoners. The objective is to study this efficacy in prison
      as well as motivations to reduce and influence of socioeconomic conditions and
      other addictions in prisoners' aspiration to stop smoking. METHODS: A prospective
      study was proposed to prisoners candidate to tobacco cessation. Assessment was
      made by questionnaires and visits to physicians working at the prison. Nicotinic
      patches were systematically proposed to patients with a starting 15 mg/16 h dose
      (or 10 mg/16 h if the dependence was low), followed by a 10 and 5 mg/16 h dose
      reduction. RESULTS: Prisoners motivated to smoking cessation (N=73) generally had
      multiaddictive behaviours and precarious socioeconomic profile. Thirty percent of
      prisoners self-reported a reduction of 50% of their cigarettes consumption until
      they left prison. Median duration of this successful treatment was 45 days.
      Median duration of treatment response for patients who relapsed in prison (15 %)
      was 75 days. No predictive factor of success was found. CONCLUSION: Tobacco
      reduction is possible in prison even if living conditions are not favourable.

PMID- 18328605
TI  - Effects of soil type, moisture content, redox potential and methyl bromide
      fumigation on Kd values of radio-selenium in soil.
AB  - Understanding the processes that determine the solid-liquid partitioning (K(d)
      value) of Se is of fundamental importance in assessing the risk associated with
      the disposal of radio-selenium-containing waste. Using a mini-column (rather than
      batch) approach, K(d) values for (75)Se were determined over time in relation to
      soil moisture content (field capacity or saturated), redox potential and methyl
      bromide fumigation (used to disrupt the soil microbial population) in three
      contrasting soil types: clay loam, organic and sandy loam. The K(d) values were
      generally in the range 50-500 L kg(-1), with mean soil K(d) increasing with
      increasing organic matter content. Saturation with water lowered the measured
      redox potentials in the soils. However, only in the sandy loam soil did redox
      potential become negative, and this led to an increase in (75)Se K(d) value in
      this soil. Comparison of the data with the Eh-pH stability diagram for Se
      suggested that such strong reduction may have been consistent with the formation
      of the insoluble Se species, selenide. These findings, coupled with the fact that
      methyl bromide fumigation had no discernible effect on (75)Se K(d) value in the
      sandy loam soil, suggest that geochemical, rather than microbial, processes
      controlled (75)Se partitioning. The inter-relations between soil moisture
      content, redox potential and Se speciation should be considered in the modelling
      and assessment of radioactive Se fate and transport in the environment.

PMID- 18328606
TI  - Comparison of a diurnal vs steady-state ozone exposure profile on growth and
      yield of oilseed rape (Brassica napus L.) in open-top chambers in the Yangtze
      Delta, China.
AB  - Most available exposure-response relationships for assessing crop loss due to
      elevated ozone (O(3)) have been established using data from chamber and open-top
      chamber experiments, using a simulated constant O(3) concentration exposure
      (square wave), which is not consistent with the diurnal variation of O(3)
      concentration that occurs in nature. We investigated the response of oilseed rape
      (Brassica napus L.) to O(3) as affected by two exposure regimes: one with a
      diurnal variation (CF100D) and another with a constant concentration (CF100).
      Although the two exposure regimes have the same mean O(3) concentration and
      accumulated O(3) concentration above 40 ppb (AOT40), our results show that O(3)
      at CF100D reduced biomass and number of pods/plant more than O(3) at CF100. Both
      O(3) exposures resulted in larger seed weights/100 pods compared to CF. Numbers
      of seeds/100 pods were reduced by CF100, while numbers of seeds/100 pods in the
      CF100D chambers were comparable to those in CF. Our results suggest that chamber
      experiments that use a constant O(3) exposure may underestimate O(3) effects on
      biomass and yields.

PMID- 18328607
TI  - Collateral benefits and hidden hazards of soil arsenic during abatement
      assessment of residential lead hazards.
AB  - Abatement of soil-lead hazards may also reduce human exposure to other soil
      toxins, thereby achieving significant collateral benefits that are not accounted
      for today. This proposition was tested with the specific case of soil-arsenic,
      where 1726 residential soil samples were collected and analyzed for lead and
      arsenic. The study found that these two toxins coexisted in most samples, but
      their concentrations were weakly correlated, reflecting the differing sources for
      each toxin. Collateral benefits of 9% would be achieved during abatement of the
      lead-contaminated soils having elevated arsenic concentrations. However, a hidden
      hazard of 16% was observed by overlooking elevated arsenic concentrations in
      soils having lead concentrations not requiring abatement. This study recommends
      that soil samples collected under HUD programs should be collected from areas of
      lead and arsenic deposition and tested for arsenic as well as lead, and that soil
      abatement decisions consider soil-arsenic as well as soil-lead guidelines.

PMID- 18328608
TI  - Elaborative processing in the Korsakoff syndrome: context versus habit.
AB  - Using a procedure of Hay and Jacoby [Hay, J. F., & Jacoby, L. L. (1999).
      Separating habit and recollection in young and older adults: Effects of
      elaborative processing and distinctiveness. Psychology and Aging, 14, 122-134],
      Korsakoff patients' capacity to encode and retrieve elaborative, semantic
      information was investigated. Habits were created during initial training,
      whereupon cued-recall memory performance was examined, with habit opposing as
      well as facilitating recollection of earlier studied words. A first group of
      patients was instructed and tested in the same way as healthy controls and showed
      poor test performance. Nevertheless, when given more processing and response
      time, additional explanation, and explicit encouragement, a second group of
      patients performed similarly to healthy controls. The results suggest that, when
      given adequate support, Korsakoff patients are able to encode and make use of
      semantic, contextual, and sequential information. Word distinctiveness, however,
      only influenced performance of controls.

PMID- 18328609
TI  - On the historical and conceptual background of the Wisconsin Card Sorting Test.
AB  - In this paper, we describe the development of the Wisconsin Card Sorting Test
      (WCST). We trace the history of sorting tasks from the studies of Narziss Ach on
      the psychology of thinking, via the work of Kurt Goldstein and Adhemar Gelb on
      brain lesioned patients around 1920 and subsequent developments, up to the actual
      design of the WCST by Harry Harlow, David Grant, and their student Esther Berg.
      The WCST thus seems to originate from the psychology of thinking
      ('Denkpsychologie'), but the test, as it is used in clinical neuropsychological
      practice, was designed by experimenters working within the behaviorist tradition.
      We also note recent developments suggesting that, contrary to the general
      impression, implicit learning may play a role in WCST-like discrimination
      learning tasks.

PMID- 18328610
TI  - Evaluation of genotoxic effects of sodium propionate, calcium propionate and
      potassium propionate on the root meristem cells of Allium cepa.
AB  - The effects of different treatments with food preservatives, sodium propionate
      (SP), calcium propionate (CP) and potassium propionate (PP), on the cytology and
      DNA content of Allium cepa were investigated. Five concentrations of these
      additives - 1000, 1500, 2000, 2500, and 3000ppm - were applied for 24, 48, and
      72h. All concentrations of these chemicals showed an inhibitory effect on cell
      division in root-tips of A. cepa and caused a decrease in mitotic index values.
      Additionally, all treatments changed the frequency of mitotic phases when
      compared with the control groups. These compounds increased chromosome
      abnormalities in test material. Among these abnormalities were C-mitosis,
      anaphase bridges, micronuclei, binucleated cells, stickiness, laggards, and
      chromosome breaks. The nuclear DNA contents decreased when compared with control
      groups.

PMID- 18328611
TI  - Subchronic toxicity study of 3-monochloropropane-1,2-diol administered by
      drinking water to B6C3F1 mice.
AB  - 3-Monochloropropane-1,2-diol (3-MCPD) is a food processing contaminant in a wide
      range of foods and ingredients and is a suspected cause of cancer. In this study,
      the 13-week toxicity of 3-MCPD was examined in B6C3F1 mice (10/sex/group)
      administered 3-MCPD doses of 0, 5, 25, 100, 200 and 400 ppm dissolved in their
      drinking water over a 13-week period. All the mice survived to the end of study.
      The mean body weight gains in the males and females given 400 ppm were
      significantly lower than those of the controls. The relative kidney weights of
      the males and females given 200 and 400 ppm were significantly higher than those
      of the controls without any corresponding histopathological changes. The sperm
      motility was lower in the 400 ppm group than the control, and there was a
      significant increase in the incidence of germinal epithelium degeneration in the
      200 and 400 ppm groups. A delayed total estrus cycle length was observed in the
      400 ppm group without any histopathological changes. Based on these results, the
      target organ was determined to be kidney, testis, and ovary. The no-observed
      adverse-effect level (NOAEL) was found to be 100 ppm (18.05 mg/kg/day for males
      and 15.02 mg/kg/day for females).

PMID- 18328612
TI  - Lead contamination in Eugenia dyeriana herbal preparations from different
      commercial sources in Malaysia.
AB  - The Drug Control Authority (DCA) of Malaysia implemented the phase three
      registration of traditional medicines on 1 January, 1992. A total of 100 products
      in various pharmaceutical dosage forms of a herbal preparation, containing
      Eugenia dyeriana, either single or combined preparations (more than one medicinal
      plant), were analyzed for the presence of lead contamination, using atomic
      absorption spectrophotometry. These samples were bought from different commercial
      sources in the Malaysian market, after performing a simple random sampling.
      Results showed that 22% of the above products failed to comply with the quality
      requirement for traditional medicines in Malaysia. Although this study showed
      that 78% of the products fully complied with the quality requirement for
      traditional medicines in Malaysia pertaining to lead, however, they cannot be
      assumed safe from lead contamination because of batch-to-batch inconsistency.

PMID- 18328613
TI  - Hexavalent chromium causes the oxidation of thioredoxin in human bronchial
      epithelial cells.
AB  - Hexavalent chromium [Cr(VI)] species such as chromates are cytotoxic.
      Inhalational exposure is a primary concern in many Cr-related industries and
      their immediate environments, and bronchial epithelial cells are directly exposed
      to inhaled Cr(VI). Chromates are readily taken up by cells and are reduced to
      reactive Cr species which may also result in the generation of reactive oxygen
      species (ROS). The thioredoxin (Trx) system has a key role in the maintenance of
      cellular thiol redox balance and is essential for cell survival. Cells normally
      maintain the cytosolic (Trx1) and mitochondrial (Trx2) thioredoxins largely in
      the reduced state. Redox Western blots were used to assess the redox status of
      the thioredoxins in normal human bronchial epithelial cells (BEAS-2B) incubated
      with soluble Na2CrO4 or insoluble ZnCrO4 for different periods of time. Both
      chromates caused a dose- and time-dependent oxidation of Trx2 and Trx1. Trx2 was
      more susceptible in that it could all be converted to the oxidized form, whereas
      a small amount of reduced Trx1 remained even after prolonged treatment with
      higher Cr concentrations. Only one of the dithiols, presumably the active site,
      of Trx1 was oxidized by Cr(VI). Cr(VI) did not cause significant GSH depletion or
      oxidation indicating that Trx oxidation does not result from a general oxidation
      of cellular thiols. With purified Trx and thioredoxin reductase (TrxR) in vitro,
      Cr(VI) also resulted in Trx oxidation. It was determined that purified TrxR has
      pronounced Cr(VI) reducing activity, so competition for electron flow from TrxR
      might impair its ability to reduce Trx. The in vitro data also suggested some
      direct redox interaction between Cr(VI) and Trx. The ability of Cr(VI) to cause
      Trx oxidation in cells could contribute to its cytotoxic effects, and could have
      important implications for cell survival, redox-sensitive cell signaling, and the
      cells' tolerance of other oxidant insults.

PMID- 18328614
TI  - Distinct effects of attention and affect on pain perception and somatosensory
      evoked potentials.
AB  - The influence of affect and attention on sensory and affective pain as well as on
      somatosensory evoked potentials in response to painful and nonpainful electrical
      stimuli was investigated in a single experimental design. Affect was induced by
      pictures from the International Affective Picture System; attention was
      manipulated by asking participants to focus attention either on the pictures or
      on the electrical stimuli. Sensory and affective pain ratings were generally
      lower during exposure to positive compared to negative and neutral pictures.
      Attention modulated only sensory pain ratings with lower ratings with an
      attention focus on pictures than with an attention focus on sensory pain. The
      N150 was modulated by picture valence, the P260 by picture arousal. Furthermore,
      the P260 was modulated by attention with highest amplitudes with an attention
      focus on the stimulus intensity. This study provides neurophysiological evidence
      that attention and affect have distinct effects on pain processing.

PMID- 18328615
TI  - Postpartum sterilization: the choice of laparoscopy or minilaparotomy?

PMID- 18328617
TI  - High-frequency subharmonic pulsed-wave Doppler and color flow imaging of
      microbubble contrast agents.
AB  - A recent study has shown the feasibility of subharmonic (SH) flow imaging at a
      transmit frequency of 20 MHz. This paper builds on these results by examining the
      performance of SH flow imaging as a function of transmit pressure. Further, we
      also investigate the feasibility of SH pulsed-wave Doppler (PWD) imaging. In
      vitro flow experiments were performed with a 1-mm-diameter wall-less vessel
      cryogel phantom using the ultrasound contrast agent Definity and an imaging
      frequency of 20 MHz. The phantom results show that there is an identifiable
      pressure range where accurate flow velocity and power estimates can be made with
      SH imaging at 10 MHz (SH10), above which velocity estimates are biased by
      radiation force effects and unstable bubble behavior, and below which velocity
      and power estimates are degraded by poor SNR. In vivo validation of SH PWD was
      performed in an arteriole of a rabbit ear, and blood velocity estimates compared
      well with fundamental (F20) mode PWD. The ability to suppress tissue signals
      using SH signals may enable the use of higher frame rates and improve sensitivity
      to microvascular flow or slow velocities near large vessel walls by reducing or
      eliminating the need for clutter filters.

PMID- 18328616
TI  - Cardiovascular assessment of fetal mice by in utero echocardiography.
AB  - To establish a developmental profile of fetal mouse cardiovascular parameters, we
      analyzed a large body of ultrasound measurements obtained by in utero
      echocardiography of C57BL/6J fetal mice from embryonic day 12.5 to 19.5 (term).
      Measurements were obtained using two-dimensional (2D), spectral Doppler and M
      mode imaging with standard clinical cardiac ultrasound imaging planes. As these
      studies were conducted as part of a large scale mouse mutagenesis screen,
      stringent filtering criteria were used to eliminate potentially abnormal fetuses.
      Our analysis showed heart rate increased from 190 to 245 beats per minute as the
      mouse fetus grew from 8 mm at embryonic day 12.5 to 18.7 mm at term. This was
      accompanied by increases in peak outflow velocity, E-wave, E/A ratio and
      ventricular dimensions. In contrast, the A-wave, myocardial performance index and
      isovolemic contraction time decreased gradually. Systolic function remained
      remarkably stable at 80% ejection fraction. Analysis of intra- and interobserver
      variabilities showed these parameters were reproducible, with most comparing
      favorably to clinical ultrasound measurements in human fetuses. A comprehensive
      database was generated comprising 23 echocardiographic parameters delineating
      fetal mouse cardiovascular function from embryonic day 12.5 to term. This
      database can serve as a standard for evaluating cardiovascular pathophysiology in
      genetically altered and mutant mouse models.

PMID- 18328618
TI  - Outcomes in urinary incontinence: reconciling clinical relevance with scientific
      rigour.
AB  - OBJECTIVES: To aid clinicians in selecting an outcome measure for the assessment
      of urinary incontinence (UI), from the perspective of both scientific rigour and
      clinical utility. METHODS: We conducted a comprehensive review of the literature
      on outcome measures for the assessment of UI in adults. Tools were classified by
      instrument type (ie, subjective measures, objective measures, clinical
      observations, quality of life, and combined instruments) and assessed for
      scientific rigour based on their psychometric properties (reliability, validity,
      responsiveness). The clinical relevance of each tool was considered in terms of
      current usage and practicality. RESULTS: The most rigorous validation processes
      were identified for quality-of-life questionnaires, including the Incontinence
      Impact Questionnaire, King's Health Questionnaire, Incontinence Quality of Life
      questionnaire, and Urogenital Distress Inventory. Bladder diaries, goal
      attainment scales, and combined measures such as the International Consultation
      on Incontinence Questionnaire appear to be more practical for use in clinics. The
      Clinical Global Impression of Improvement is the outcome most widely used
      clinically, but least well validated. CONCLUSIONS: To elevate the level of
      outcome assessment for UI to meet that of other urology specialties, it is
      necessary to reconcile the realities of clinical practice with the scientific
      rigour of UI research, and to mainstream outcome measures that are reciprocally
      translatable between the two settings.

PMID- 18328619
TI  - Regulation of male fertility by the endocannabinoid system.
AB  - Mammalian conception is a complex process regulated by both sexual behavior and
      reproductive performance. Alcohol, marijuana and tobacco are among the main
      factors which affect negatively fertility in women and men. Several studies have
      demonstrated that marijuana impairs the male copulatory activity, and that
      smokers of this illegal drug show reduced fertility due, for instance, to
      decrease in sperm concentration, defective sperm function or alteration of sperm
      morphology. The discovery of endocannabinoids and all components responsible for
      their metabolism has allowed to collect valuable information on the effects of
      these endogenous lipids, able to mimic the actions of delta-9
      tetrahydrocannabinol (THC), in reproductive functions. The purpose of this review
      is to describe the actions of cannabinoids and endocannabinoids on the control of
      procreation and hormonal release during the fertilization process in males.

PMID- 18328620
TI  - Study on thermal decomposition characteristics of AIBN.
AB  - It is found that the results such as observed in the differential scanning
      calorimeter (DSC), which show the major thermal decomposition (TD) of a self
      reactive material, lack the detail to reveal what happens at the initial stage of
      a reaction. The reaction at this stage is corresponding to the handling condition
      of storage or transportation, often possibly having the potential to be developed
      to a runaway reaction. This paper examined and compared the thermal behaviors of
      AIBN at various working conditions in calorimeters and Dewar vessels. The
      mechanism that affects the initial reaction and self-heating behavior of the
      given material was clarified. Near its onset decomposition temperature, physical
      processes, such as sublimation or melting interfered the initial reaction of
      AIBN. The mutuality of the physical effect and the chemical reaction made AIBN
      behave differently under different measuring conditions, and as the result, quasi
      autocatalysis or TD possibly occurs in the same sample at the handling
      temperature range. The heat accumulation storage tests in two Dewar vessels
      presented completely different self-heating behaviors due to this mechanism and
      heat transfer capability of the vessels.

PMID- 18328621
TI  - Modelling phenol biodegradation by activated sludges evaluated through
      respirometric techniques.
AB  - In this paper respirometric techniques were used to study the effect of pH,
      phenol and dissolved oxygen (DO) concentrations on the phenol biodegradation
      kinetics by activated sludges. In addition, a mathematical model was developed to
      interpret the obtained respirometric curves. Closed respirometer experiments
      showed that phenol inhibited the respiration rate of unacclimated sludges. On the
      contrary, oxygen uptake rate (OUR) of phenol acclimated sludges exhibiting the
      typical Haldane's substrate inhibition curve. The Monod equation adequately
      represented the relation between OUR of acclimated biomass and DO concentration.
      Within the tested pH range (4-12) the oxygen saturation coefficient was
      independent of pH. On the contrary, the maximum OUR was strongly affected by the
      pH, being its maximum between 9.5 and 10.5. Open respirometer experiments shows
      that as pH decreased from 10.2 to 5.8, the maximum OUR also decreased, in
      accordance with the trend observed in the closed respirometer experiments.
      Although the respiration rate of phenol degrading bacteria was strongly affected
      by pH, a constant phenol oxidation coefficient was observed within the studied pH
      interval. A mathematical model was proposed to interpret the open respirometry
      curves. The coefficients of the model were estimated using both pseudo steady
      state and dynamic conditions for different biomass concentrations. The model
      adequately predicted the whole OUR and DO profiles as a function of time during
      the biodegradation of phenol under different DO conditions. The mathematical
      model proposed in the present work is useful for predicting transient responses
      such as substrate concentration and DO concentrations as a function of time in
      bioreactors treating phenolic wastewaters under an overload of phenolic
      compounds.

PMID- 18328622
TI  - Reductive transformation of 2,4,6-trinitrotoluene, hexahydro-1,3,5-trinitro-1,3,5
      triazine, and nitroglycerin by pyrite and magnetite.
AB  - Reductive transformation of 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX), and nitroglycerin (NG) by pyrite (FeS(2)) and magnetite
      (Fe(3)O(4)) was investigated to determine the role of Fe(II)-bearing minerals on
      the fate of toxic explosives in Fe/S-rich natural environment. Results from batch
      experiments showed that 65% of TNT and 45% of RDX were transformed from solution
      in the presence of pyrite under pH 7.4 buffered conditions within 32 days.
      Without a buffered solution, transformation of TNT and RDX decreased. NG was
      continuously and rapidly transformed by pyrite under both conditions. Complete
      removal of NG was achieved in 32 days under buffered conditions. NH(4)(+) was
      identified as a reduction product for RDX and NG in the pyrite-water system.
      Reductive transformation of RDX and NG by magnetite was slower than that by
      pyrite. The results suggest that abiotic transformation of the explosives by
      pyrite and magnetite may be considered when determining the fate of explosives in
      Fe/S-rich subsurface environments.

PMID- 18328623
TI  - An improved probit method for assessment of domino effect to chemical process
      equipment caused by overpressure.
AB  - Overpressure is one important cause of domino effect in accidents of chemical
      process equipments. Damage probability and relative threshold value are two
      necessary parameters in QRA of this phenomenon. Some simple models had been
      proposed based on scarce data or oversimplified assumption. Hence, more data
      about damage to chemical process equipments were gathered and analyzed, a
      quantitative relationship between damage probability and damage degrees of
      equipment was built, and reliable probit models were developed associated to
      specific category of chemical process equipments. Finally, the improvements of
      present models were evidenced through comparison with other models in
      literatures, taking into account such parameters: consistency between models and
      data, depth of quantitativeness in QRA.

PMID- 18328624
TI  - l-3-n-Butylphthalide ameliorates beta-amyloid-induced neuronal toxicity in
      cultured neuronal cells.
AB  - l-3-n-Butylphthalide (l-NBP), as an anti-cerebral ischemia agent, has been shown
      to have therapeutic effects on learning and memory deficits induced by chronic
      cerebral hypoperfusion and Abeta intracerebroventricular infusion in rats. In the
      present study, we investigated the neuroprotective effects of l-NBP on beta
      amyloid (Abeta)25-35-induced neuronal death/apoptosis and potential mechanisms in
      rat hippocampal neurons and human neuroblastoma SH-SY5Y cells. Abeta25-35
      significantly reduced cell viability and increased the number of apoptotic-like
      cells, indicating that Abeta25-35-induced neurotoxicity. In addition, tau protein
      hyperphosphorylation was found to increase after Abeta exposure. All of these
      phenotypes induced by Abeta25-35 were markedly reversed by l-NBP. Pretreatment
      with l-NBP prior to Abeta25-35 exposure significantly elevated cell viability,
      and reduced Abeta25-35-induced nuclear fragmentation and early apoptosis.
      Furthermore, immunoreactivity for hyperphosphorylation tau protein was
      significantly decreased by l-NBP treatment. Our results suggest that l-NBP may
      protect neurons against Abeta-induced neurotoxicity via inhibiting tau protein
      hyperphosphorylation.

PMID- 18328625
TI  - Playback of 22-kHz and 50-kHz ultrasonic vocalizations induces differential c-fos
      expression in rat brain.
AB  - Rodent ultrasonic vocalizations, which serve as sensitive measures in a number of
      relevant individual and social behaviours, have become increasingly interesting
      for biopsychological studies on emotion and motivation. Of these, high frequency
      (50-kHz) ultrasonic vocalizations can index a positive emotional state, and
      induce approach, whereas low frequency (22-kHz) ultrasonic vocalizations can
      induce avoidance and may index anxiety, since they are emitted during various
      unconditioned and conditioned aversive situations. While cholinergic and
      dopaminergic systems have been implicated, specific neural substrates that sub
      serve these vocalization-dependent states remain to be elucidated. Using c-fos
      immunocytochemistry, we revealed neural activity in brain areas of naive male
      Wistar rats in response to playback of 22-kHz and flat and frequency-modulated 50
      kHz ultrasonic vocalizations. Presentation of background noise or no acoustic
      stimulus at all constituted the controls. Playback of 50-kHz ultrasonic
      vocalizations led to approach behaviour. Acoustically stimulated animals
      demonstrated differential activation in auditory areas, with a frequency
      dependent activation in the auditory cortex. Specific forebrain, thalamic,
      hypothalamic and brainstem areas were also activated differentially. While 50-kHz
      playback induced sparse fos-like immunoreactivity in frontal association cortex,
      nucleus accumbens, thalamic parafascicular and paraventricular nuclei, 22-kHz
      playback elicited c-fos expression in the perirhinal cortex, amygdalar nuclei and
      the periaqueductal gray. This study unveils neural substrates that are activated
      during ultrasonic playback perception, which could sub-serve the affective states
      elicited by these vocalizations.

PMID- 18328626
TI  - Extracellular signal-regulated kinase involved in NGF/VEGF-induced
      neuroprotective effect.
AB  - Compelling evidence has shown that extracellular signal-regulated kinase (ERK) is
      widely expressed in many tissues, including the brain. In the present work, we
      investigated the temporospatial alterations of ERK1 immunoreactivity in
      hippocampus and perifocal cortex, and the expression involved in NGF/VEGF-induced
      neuroprotective effect. We demonstrated that ERK1 expression was first increased
      in hippocampal CA3/DG 1 h after reperfusion, then it was also increased 6 h after
      reperfusion in other brain regions, with a peak at day 1-3, and then gradually
      decreased to basal level at day 14. The expression of caspase-3 was strongly
      increased 1 h after reperfusion, with peak demonstrated at 3d. NGF/VEGF
      significantly inhibited the expression of ERK1 and caspase-3. These results
      suggest that ERK1 signaling pathway may be involved in neuronal cell death and
      NGF/VEGF-induced neuroprotective effect and there appeared an association between
      ERK and caspase-3. Inhibition of the ERK signaling pathway might therefore
      provide an efficient way to prevent neuronal cell death after ischemic cerebral
      injuries.

PMID- 18328627
TI  - Localization of glial aquaporin-4 and Kir4.1 in the light-injured murine retina.
AB  - Excessive light causes damage to photoreceptor and pigment epithelial cells, and
      a local edema in the outer retina. Since Muller glial cells normally mediate the
      osmohomeostasis in the inner retina (mainly via channel-mediated transport of
      potassium and water), we determined whether retinal light injury causes an
      alteration in the retinal localization of glial water (aquaporin-4) and potassium
      (Kir4.1) channels, and in the potassium conductance of Muller cells. Mice were
      treated with bright white light (intensity, 15,000lx) for 2h. Light treatment
      results in Muller cell gliosis as indicated by the enhanced staining of the glial
      fibrillary acidic protein and an increase in the cell membrane area reflecting
      cellular hypertrophy. In light-injured retinas, the immunostaining of the
      photoreceptor water channel aquaporin-1 disappeared along with the degeneration
      of the outer retina, and the outer nuclear layer contained large spherical bodies
      representing photoreceptor nuclei which were fused together. The immunostainings
      of the aquaporin-4 and Kir4.1 proteins were increased in the outer retina after
      light treatment. Since the amplitude of the potassium currents of Muller cells
      remained largely unaltered, the increase in the Kir4.1 immunostaining is supposed
      to be caused by a redistribution of the channel protein. The data indicate that
      Muller glial cells respond to excessive light with an alteration in the
      localization of Kir4.1 and aquaporin-4 proteins; this alteration is thought to be
      a response to the edema in the outer retina and may support the resolution of
      edema.

PMID- 18328628
TI  - Characterization of JEOL 2100F Lorentz-TEM for low-magnification electron
      holography and magnetic imaging.
AB  - We present results that characterize the performance and capabilities of the JEOL
      2100F-LM electron microscope to carry out holography and quantitative magnetic
      imaging. We find the microscope is well-suited for studies of magnetic materials,
      or for semi-conductor dopant profiling, where a large hologram width (
      approximately 1 microm) and fine fringe spacing ( approximately 1.5 nm) are
      obtained with good contrast ( approximately 20%). We present, as well,
      measurements of the spherical aberration coefficient Cs=(108.7+/-9.6)mm and
      minimum achievable focal step delta f=(87.6+/-1.4)nm for the specially designed
      long-focal-length objective lens of this microscope. Further, we detail
      experiments to accurately measure the optical parameters of the imaging system
      typical of conventional holography setup in a transmission electron microscope.
      The role played by astigmatic illumination in the hologram formation is also
      assessed with a wave-optical model, which we present and discuss. The
      measurements obtained for our microscope are used to simulate realistic
      holograms, which we compare directly to experimental holograms finding good
      agreement. These results indicate the usefulness of measuring these optical
      parameters to guide the optimization of the experimental setup for a given
      microscope, and to provide an additional degree of practical experimental
      possibility.

PMID- 18328629
TI  - Parasitic infections in dairy cattle around Hanoi, northern Vietnam.
AB  - In northern Vietnam, dairy cattle are mainly managed in small-scale farms, where
      animals are kept confined and feeding occurs by cut and carry methods. In the
      present study the occurrence of parasitic infections was examined in five
      provinces around Hanoi. A total of 201 farms were visited, and 334 stool and 239
      blood samples were collected from calves younger than 3 months, animals between 3
      and 24 months and adult cows. Furthermore, 254 milk samples were collected from
      lactating animals. Coproscopical examination indicated a high prevalence of
      nematode eggs (Cooperia spp., Haemonchus and Oesophagostomum spp.) in animals
      (n=176) between 3 and 24 months (66%) and in adult cows (n=90; 54%). In these age
      groups the prevalence of Fasciola was 28% and 39%, respectively, and for
      Paramphistomum the prevalence was 78% and 82%, respectively. Fifty percent of the
      calves younger than 3 months (n=68) were positive for Giardia, and none for
      Cryptosporidium. Most Giardia isolates were identified as the non-zoonotic G.
      duodenalis assemblage E on the beta-giardin gene. The blood samples were examined
      with commercially available Svanovir((R))Elisa's for the presence of Anaplasma
      marginale and Babesia bigemina specific antibodies, and a prevalence of 28% and
      54% was found, respectively. In the milk samples Neospora caninum specific
      antibodies (Svanovir((R))Elisa) were detected in 30% of the lactating animals.
      The present study demonstrates that parasitic infections occur frequently in
      dairy cattle around Hanoi although animals are mainly kept confined, and
      indicates that further research on the economic impact of these infections is
      needed.

PMID- 18328630
TI  - Prevalence of Babesia canis, Borrelia afzelii, and Anaplasma phagocytophilum
      infection in hard ticks removed from dogs in Warsaw (central Poland).
AB  - The purposes of this study were to specify the occurrence and prevalence of
      Babesia canis, Borrelia burgdorferi sensu lato, and Anaplasma phagocytophilum in
      ticks removed from dogs in Warsaw, and to determine the Borrelia species
      occurring in Ixodes ricinus ticks. Among 590 collected ticks, 209 were identified
      as I. ricinus, and 381 as Dermacentor reticulatus. DNA of B. canis was detected
      in 11% of D. reticulatus ticks. We found that 6.2% of I. ricinus ticks harbored
      B. burgdorferi s.l. specific DNA and 2.9% harbored A. phagocytophilum DNA. In
      these samples sequencing of the detected Borrelia amplicon confirmed infection
      with Borrelia afzelii genospecies. New sequences were submitted to the GenBank
      database (accession no. EU152128, EU152127, EU152126). This work is the first
      detection of B. afzelii and A. phagocytophilum in ticks from Warsaw, and the
      first survey for the prevalence of B. canis, B. afzelii, and A. phagocytophilum
      in ticks in central Poland.

PMID- 18328631
TI  - Functional changes in baroreceptor afferent, central and efferent components of
      the baroreflex circuitry in type 1 diabetic mice (OVE26).
AB  - Baroreflex control of heart rate (HR) is impaired in diabetes mellitus. We
      hypothesized that diabetes mellitus induced functional changes of neural
      components at multiple sites within the baroreflex arc. Type 1 diabetic mice
      (OVE26) and FVB control mice were anesthetized. Baroreflex-mediated HR responses
      to sodium nitroprusside- (SNP) and phenylephrine- (PE) induced mean arterial
      blood pressure (MAP) changes were measured. Baroreceptor function was
      characterized by measuring the percent (%) change of baseline integrated aortic
      depressor nerve activity (Int ADNA) in response to SNP- and PE-induced MAP
      changes. The HR responses to electrical stimulation of the left aortic depressor
      nerve (ADN) and the right vagus nerve were assessed. Compared with FVB control
      mice, we found in OVE26 mice that (1) baroreflex-mediated bradycardia and
      tachycardia were significantly reduced. (2) The baroreceptor afferent function in
      response to MAP increase did not differ, as assessed by the parameters of the
      logistic function curve. But, the inhibition of Int ADNA in response to MAP
      decrease was significantly attenuated. (3) The maximum amplitude of bradycardic
      responses to right vagal efferent stimulation was augmented. (4) In contrast, the
      maximum amplitude of bradycardic responses to left ADN stimulation was decreased.
      Since Int ADNA was preserved in response to MAP increase and HR responses to
      vagal efferent stimulation were augmented, we conclude that a deficit of the
      central mediation of baroreflex HR contributes to the overall attenuation of
      baroreflex sensitivity in OVE26 mice. The successful conduction of physiological
      experiments on the ADN in OVE26 mice may provide a foundation for the
      understanding of cellular and molecular mechanisms of diabetes-induced cardiac
      neuropathy.

PMID- 18328632
TI  - Separation of A- versus C-nociceptive inputs into spinal-brainstem circuits.
AB  - This study was designed to determine the organization of nociceptive inputs with
      different behavioral significance into spinal-brainstem circuits in the rat.
      Induction of Fos protein was used to localize spinal dorsal horn and hypothalamic
      neurons activated by noxious heating of the hind paw dorsum at rates known to
      preferentially activate C- or A-heat nociceptors. This was combined with
      retrograde transport of cholera toxin subunit B from the dorsolateral/lateral-
      (DL/L-) or the ventrolateral- (VL-) periaqueductal gray (PAG) in order to map the
      organization of A- and C-fiber input to spinal-brainstem circuits. The majority
      of dorsal horn heat-activated neurons were located in laminae I and II. A
      significantly larger proportion of C-fiber-activated neurons projected to the VL
      PAG (P<0.05) compared with its DL/L-sector. In contrast, there was no columnar
      separation in the projections of A-fiber-activated neurons. However, a
      significantly greater proportion of A-fiber-activated neurons (P<0.05) were
      retrogradely labeled from the DL/L-PAG, when compared with C-fiber-activated
      neurons. A large proportion (25-50%) of A- and C-fiber-activated neurons in the
      lateral spinal nucleus projected to the PAG. A-fiber-activated neurons were found
      throughout the rostral hypothalamus but those projecting to the PAG were focused
      in the lateral area of the anterior hypothalamus (LAAH), from where approximately
      20% projected to the VL-PAG, which was significantly more than to the DL/L PAG
      (P<0.05). We hypothesize that the organization of A- versus C-fiber inputs to the
      PAG enables the coordination of coping strategies appropriate to meet the demands
      imposed by these different noxious stimuli. Hypothalamic-PAG projections
      activated by A-fiber inputs did not reflect this level of organization and we
      suggest that this may relate to their role in thermoregulation as opposed to
      autonomic responses to particular nociceptive inputs.

PMID- 18328633
TI  - Dual-stream modulation failure: a novel hypothesis for the formation and
      maintenance of delusions in schizophrenia.
AB  - Delusions, a cardinal feature of schizophrenia, are characterized by the
      development and preservation of false beliefs despite reason and evidence to the
      contrary. A number of cognitive models have made important contributions to our
      understanding of delusions, though it remains unclear which core cognitive
      processes are malfunctioning to enable individuals with delusions to form and
      maintain erroneous beliefs. We propose a modified dual-stream processing model
      that provides a viable and testable mechanism that can account for this
      debilitating symptom. Dual-stream models divide decision-making into two streams:
      a fast, intuitive and automatic form of processing (Stream 1); and a slower,
      conscious and deliberative process (Stream 2). Our novel model proposes two key
      influences on the way these streams interact in everyday decision-making:
      conflict and emotion. Conflict: in most decision-making scenarios one obvious
      answer presents itself and the two streams converge onto the same conclusion.
      However, in instances where there are competing alternative possibilities, an
      individual often experiences dissonance, or a sense of conflict. The detection of
      this conflict biases processing towards the more deliberative Stream 2. Emotion:
      highly emotional states can result in behavior that is reflexive and action
      oriented. This may be due to the power of emotionally valenced stimuli to bias
      reasoning towards Stream 1. We propose that in schizophrenia, an abnormal
      response to these two influences results in a pathological schism between Stream
      1 and Stream 2, enabling erroneous intuitive explanations to coexist with
      contrary logical explanations of the same event. Specifically, we suggest that
      delusions are the result of a failure to reconcile the two streams due to both a
      failure of conflict to bias decision-making towards Stream 2 and an accentuated
      emotional bias towards Stream 1.

PMID- 18328634
TI  - [Socioeconomic disparities for maternal serum screening of Down's syndrome:
      trends between 1998 and 2003 in France].
AB  - OBJECTIVES: To compare trends in the use of and the opportunity for making an
      informed choice, regarding maternal serum screening for Down's syndrome. METHODS:
      Data were based on the national perinatal surveys of 1998 and 2003, which
      comprise representative samples of births in France. We used logistic regression
      models and likelihood ratio tests for testing the statistical significance of
      interactions between time trends and socioeconomic factors. RESULTS: We found a
      generalized increase between 1998 and 2003 in both the use of screening and in
      the opportunity for making an informed choice. The use of screening increased
      more however, for women with primary or no education (OR=3.0; 95% CI, 2.2-4.1) as
      compared with those with education levels beyond a high school diploma (OR: 1.8;
      95% CI, 1.7-2.0). On the contrary, trends in informed choice were comparable
      across socioeconomic groups. Hence, disparities in the opportunity for informed
      choice were essentially unchanged. CONCLUSIONS: The use of serum screening, and
      the opportunity for informed choice regarding the test, became more widespread
      for women from all socioeconomic categories between 1998 and 2003. These trends
      were accompanied by a decrease in socioeconomic disparities in the use of
      screening but not in the opportunity for making an informed choice.

PMID- 18328635
TI  - Optimization of the use of ciprofloxacin.
AB  - AIMS: To compare mutant prevention concentration (MPC) of ciprofloxacin and time
      killing curve with regards to 11 genotyped Escherichia coli. METHOD: MICs were
      determined using the E-test method. Time-killing studies were performed in
      accordance with the NCCLS guidelines. The genes gyrA, gyrB, parC, parE and marR
      were amplified by PCR and sequenced. The MPC was defined as the lowest antibiotic
      concentration preventing the growth of resistant colonies when 10(10) CFU/mL were
      spread on a solid medium. RESULTS: Strains with no genes gyrA, gyrB, parC, parE
      and marR mutation presented MIC less or equal to 0.023 mg/L and MPC less or equal
      to 0.25 mg/L. Strains with two mutations (gyrA and parC) presented MIC equal to
      1.5 mg/L and MPC equal to 4 mg/L. Strains with one mutation (gyrA) presented MIC
      less or equal to 0.75 mg/L, but MPC ranged from 0.5 to 6 mg/L depending of the
      MIC of ciprofloxacin. The time-killing curves for ciprofloxacin showed a
      bactericidal activity of 0.25 mg/L in 1h for strains without mutation, compared
      with a bactericidal activity of 2 and 4 mg/L in 4h for strains with one and two
      mutations, respectively. CONCLUSION: For strains of E. coli resistant to
      nalidixic acid, it was necessary to evaluate the MIC of ciprofloxacin in order to
      asses the optimal dosage of ciprofloxacin.

PMID- 18328636
TI  - Male infanticide and paternity analyses in a socially natural herd of
      Przewalski's horses: sexual selection?
AB  - The sexual selection hypothesis explains infanticide by males in many mammals. In
      our 11-year study, we investigated this hypothesis in a herd of Przewalski's
      horses where we had witnessed infanticidal attacks. Infanticide was highly
      conditional and not simply linked to takeovers. Attacks occurred in only five of
      39 cases following a takeover, and DNA paternity revealed that, although
      infanticidal stallions were not the genetic fathers in four cases out of five,
      stallions present at birth did not significantly attempt to kill unrelated foals.
      Infanticide did not reduce birth intervals; only in one case out of five was the
      infanticidal stallion, the father of the next foal; mothers whose foals were
      attacked subsequently avoided associating with infanticidal stallions. Therefore,
      evidence for the sexual selection hypothesis was weak. The "human disturbance"
      hypothesis received some support, as only zoo bred stallions which grew up in
      unnatural social groups attacked foals of mares which were pregnant during
      takeovers.

PMID- 18328637
TI  - Protective effect against alcohol dependence of the thermolabile variant of
      MTHFR.
AB  - BACKGROUND: Hyperhomocysteinemia is frequently observed in alcohol-dependent
      subjects, in particularly in those with marked withdrawal symptoms. The common
      C677T transition on the methylenetetrahydrofolate reductase (MTHFR) gene
      influences homocysteinemia. Our objective was to study the prevalence of the
      MTHFR C677T polymorphism in alcohol-dependent subjects and the influence of this
      polymorphism on symptoms associated with alcoholism. METHODS: MTHFR C677T
      polymorphism was determined in 93 control subjects and 242 alcohol-dependent
      subjects. Serum homocysteine, folate and vitamin B12 levels together with hepatic
      biological parameters were determined in the control and alcohol-dependent
      subjects. RESULTS: Hyperhomocysteinemia is frequently observed in alcohol
      dependent subjects, particularly in those with marked withdrawal symptoms.
      Alcohol-dependent subjects showed a significant decrease in MTHFR 677TT
      prevalence (9%, 21/242) compared to controls (18%, 17/93) (p<0.02). The relative
      risk estimated as an odds ratio for alcoholism in subjects with the TT genotype
      is 0.42 (odd ratio 95% confidence interval, 0.21-0.83). Moreover, drinkers with
      TT genotype presented lower values for markers of alcohol misuse (p<0.05), better
      liver function tests, a lower frequency of relapses and no marked withdrawal
      symptoms as assessed by the Lesch typology. CONCLUSION: MTHFR 677TT genotype
      could play a protective role against alcohol dependence. Moreover, when subjects
      with MTHFR 677TT genotype become dependent to alcohol, they seem to constitute a
      subgroup of alcoholic patients with a decreased risk for developing neurotoxic
      withdrawal symptoms and hepatic toxicity.

PMID- 18328638
TI  - Community program therapist adherence and competence in motivational enhancement
      therapy.
AB  - The extent to which clinicians in addiction treatment programs can implement
      empirically validated therapies with adequate fidelity that can be discriminated
      from standard counseling has rarely been evaluated. We evaluated the treatment
      adherence and competence of 35 therapists from five outpatient community programs
      who delivered either a three-session adaptation of motivational enhancement
      therapy (MET) or an equivalent number of drug counseling-as-usual sessions to 461
      clients within a National Institute on Drug Abuse Clinical Trial Network multi
      site effectiveness protocol. MET therapists were carefully prepared to implement
      MET using a combination of expert-led intensive workshop training followed by
      program-based clinical supervision. Independent rating of sessions demonstrated
      that the adherence and competence items were very reliable (mean interclass
      correlation coefficients for adherence=.89 and competence=.81) and converged to
      form two a priori defined skill factors conceptually related to motivational
      interviewing. Moreover, the factors discriminated between MET therapists and
      those who delivered drug counseling-as-usual sessions in predicted ways, and were
      significantly related to in-session change in client motivation and some client
      treatment outcomes (percent negative drug urine screens). These findings
      demonstrate the reliability and validity of evaluating motivational interviewing
      fidelity and suggest that the combination of expert-led workshops followed by
      program-based clinical supervision may be an effective method for disseminating
      motivational interviewing in community treatment programs.

PMID- 18328639
TI  - Abuse liability assessment of atomoxetine in a drug-abusing population.
AB  - BACKGROUND: Atomoxetine is a non-amphetamine medication approved to treat ADHD in
      children, adolescents, and adults. Previous studies demonstrated low abuse
      potential for atomoxetine in recreational drug users. This study assessed the
      abuse potential of atomoxetine in stimulant-preferring drug abusers compared to
      methylphenidate and phentermine as positive controls and desipramine and placebo
      as negative controls. METHODS: Forty male and female, 32-53 years old stimulant
      preferring drug abusers completed this balanced Latin-square designed study.
      Subjects received acute, double-blind doses of placebo, desipramine (100 and 200
      mg), methylphenidate (90 mg), phentermine (60 mg), and atomoxetine (45, 90, and
      180 mg). Subjective and physiological effects were collected for 24 h following
      each drug treatment. RESULTS: Methylphenidate and phentermine were liked
      significantly more than placebo, atomoxetine, or desipramine. No atomoxetine dose
      was liked significantly more than placebo and liking scores for atomoxetine were
      similar to, or significantly lower than, desipramine, as assessed by the Drug
      Rating Questionnaire-Subject. While atomoxetine 45 and 180 mg did not
      significantly change any Addiction Research Center Inventory (ARCI) scores,
      atomoxetine 90 mg significantly increased A and BG stimulant scores of the ARCI
      and both methylphenidate and phentermine produced greater A and BG increases than
      any atomoxetine dose and also increased MBG (euphoria) scores relative to
      placebo. CONCLUSIONS: Atomoxetine has significantly less abuse liability than
      methylphenidate or phentermine and no greater abuse liability than desipramine.

PMID- 18328640
TI  - Brain levels of dextromethorphan and the intensity of opioid withdrawal in mice.
AB  - Consistent with their antagonistic actions at N-methyl-D-aspartate type glutamate
      receptors, dextromethorphan (DXM) and its metabolite, dextrorphan (DXT) decrease
      the intensity of opioid withdrawal syndrome. Since quinidine (QND) affects CYP2D6
      mediated metabolism and P-glycoprotein governed transport, we sought to determine
      whether co-treatment with QND would affect brain levels of DXM and DXT as well as
      the effect of these compounds on opioid withdrawal syndrome in mice. We found
      that DXM dose dependently inhibited the intensity of opioid withdrawal syndrome
      and that there was a tendency for a further decrease when QND was co-administered
      with DXM. Administration of 30 mg/kg of DXM resulted in higher brain levels of
      DXM and DXT than administration of 10 mg/kg of DXM, but much lower DXT levels
      than that produced by 30 mg/kg of DXT. Co-treatment with QND resulted in higher
      brain levels of DXM (but not DXT) suggesting that QND produces an increase in the
      brain availability of DXM. In summary, brain levels of DXM were inversely
      correlated with the intensity of opioid withdrawal syndrome. QND induced
      increased brain levels of DXM tend to attenuate the intensity of opioid
      withdrawal syndrome. We suggest that it is DXM, rather than DXT, that is
      responsible for the attenuating effect on the intensity of opioid withdrawal
      syndrome, and that the beneficial action of QND on the effect of DXM should be
      more pronounced in humans.

PMID- 18328641
TI  - Comparing the validity of the Cigarette Dependence Scale and the Fagerstrom Test
      for Nicotine Dependence.
AB  - BACKGROUND: We compared the validity of the Cigarette Dependence Scale (CDS-12)
      and of the Fagerstrom Test for Nicotine Dependence (FTND) in daily cigarette
      smokers. METHODS: Internet survey in 2004-2007. Eight days and 6 weeks after
      answering these two dependence questionnaires, participants indicated their
      smoking status and answered the Cigarette Withdrawal Scale and the Smoking Self
      Efficacy Questionnaire. We used the Mini International Neuropsychiatric Interview
      (MINI) to assess nicotine dependence as defined in DSM-IV. RESULTS: There were
      13,697 participants at baseline, 1113 (8%) after 8 days and 435 (3%) after 6
      weeks. CDS-12, but not FTND, predicted smoking cessation after 8 days (odds
      ratio=1.20 per standard deviation unit, p=0.03) and 6 weeks (odds ratio=1.34,
      p=0.01). In participants who had quit smoking after 8 days, CDS-12 was a better
      predictor of craving (beta=0.30, p<0.001), than FTND (beta=0.14, p<0.01). After 8
      days, self-efficacy in quitters was predicted by CDS-12 (beta=-0.16, p=0.02), but
      not by FTND (beta=-0.05, p=0.3). CDS-12 was more strongly associated than FTND
      with DSM-defined dependence measured by MINI: area under the Receiver Operating
      Characteristic (ROC) curve=0.72 (95% confidence interval=0.70-0.73). For FTND,
      the area under ROC=0.64 (0.63-0.66). CONCLUSIONS: CDS-12 performed better than
      FTND on tests of predictive and construct validity.

PMID- 18328642
TI  - Increase in anger symptoms after smoking cessation predicts relapse.
AB  - Smokers tend to increase their cigarette consumption during angry states. We
      sought to determine whether increases in post-quit anger symptoms predict relapse
      among smokers who had received 8-weeks of smoking cessation treatment (21 mg
      nicotine patch+smoking cessation counseling). The 15-item state anger assessment
      [from Spielberger, C., 1999. STAXI-2: the state trait anger expression inventory
      professional manual, Odessa, FL] was administered at pre-treatment (2 weeks
      before the target quit date; TQD) and 1 week after the TQD. Abstinence at 8-weeks
      post-quit was biochemically verified using carbon monoxide. Smokers who reported
      increases in pre- to post-quit state anger levels (n=117) were significantly more
      likely to relapse by 8-weeks after treatment as compared to smokers whose anger
      did not change or decreased after quitting (n=130) (OR=1.06; CI=1.01-1.10;
      p=0.01). Furthermore, smokers with increased post-quit anger relapsed almost
      twice as quickly than those who did not have an increase in post-quit anger
      symptoms (HR=1.98; CI: 1.32-2.96; p=0.001). These data suggest that anger may be
      an important withdrawal symptom that influences liability to relapse. Future
      studies are needed to evaluate treatment strategies that effectively help smokers
      reduce and manage post-quit anger.

PMID- 18328643
TI  - Characterization of a 1-aminocyclopropane-1-carboxylate synthase gene from
      loblolly pine (Pinus taeda L.).
AB  - 1-Aminocyclopropane-1-carboxylate (ACC) synthase catalyzes what is typically the
      rate-limiting step in the biosynthesis of ethylene, a gaseous plant growth
      regulator that plays numerous roles in the growth and development of higher
      plants. Although ACC synthase genes have been characterized from a wide variety
      of angiosperm plant species, no ACC synthase genes have been described previously
      for gymnosperms. Evidence suggests that ethylene helps to regulate wood formation
      in trees, and may also signal for the metabolic shifts that lead to compression
      wood formation on the undersides of branches and leaning stems in gymnosperm
      trees. Since compression wood is an inferior feedstock for the manufacturing of
      most wood products, a better understanding of the factors influencing its
      formation could lead to substantial economic benefits. This study describes the
      isolation and characterization of a putative ACC synthase gene, PtaACS1, from
      loblolly pine (Pinus taeda L.), an important commercial forest tree species. Also
      described is an apparent splice variant of PtaACS1 (PtaACS1s) that is missing 138
      bp from the 5' end of the transcript, including bases that encode a conserved
      amino acid residue considered critical for ACC synthase activity. The two
      sequences share interesting homologies with a group of plant aminotransferases,
      in addition to ACC synthases, but structural models and the conservation of
      critical catalytic amino acid residues strongly support PtaACS1 as encoding an
      active ACC synthase. The two transcripts were differentially expressed in various
      tissues of loblolly pine, as well as in response to perturbations of pine
      seedling stems. Transcript levels of this ACC synthase gene increased rapidly in
      response to bending stress but returned to near starting levels within 30 min. It
      remains unclear to what extent bending-induced expression of this gene product
      plays a role in compression wood formation.

PMID- 18328644
TI  - Two USA Ehrlichia spp. cause febrile illness in goats.
AB  - Ehrlichia spp. are not currently recognized as a cause of illness in goats in the
      USA, but three Ehrlichia are enzootic in lone star ticks (Amblyomma americanum)
      in the eastern USA, and related bacteria in other countries cause illness in
      goats. We exposed naive goats to Ehrlichia-infected Amblyomma and demonstrated
      that infection and clinical illness can be caused by two USA species, E. ewingii
      and the recently discovered Panola Mountain Ehrlichia sp. Clinical features in
      all five goats are described; ehrlichioses were associated with pyrexia, serous
      nasal discharge, inappetance, lethargy, decreased alkaline phosphatase, and, in
      most cases, neutropenia. Goats remained chronically infected for several months
      following exposure to ehrlichiae and transmitted the pathogens to uninfected
      ticks. In the eastern USA, undifferentiated febrile illness in goats might be
      caused by previously unrecognized ehrlichial infections, and pastures housing
      infected goats could become infested with a large number of infected ticks.

PMID- 18328645
TI  - Proliferative dermatitis in a loggerhead turtle, Caretta caretta, and a green
      turtle, Chelonia mydas, associated with novel papillomaviruses.
AB  - A subadult loggerhead turtle, Caretta caretta, presented with generalized small,
      white, raised lesions over its neck, shoulders, and all four flippers. A juvenile
      green turtle, Chelonia mydas, recently treated for fibropapillomatosis, presented
      with four similar localized lesions on one flipper. To diagnose the conditions,
      biopsies of the lesions were taken for histopathology, electron microscopy, and
      molecular diagnostics. Histopathologic findings were similar in the two turtles
      and skin lesions were characterized by multifocal areas of epidermal hyperplasia
      accompanied by variation and abnormalities in the nuclear morphology of
      keratinocytes and a few intranuclear inclusions in some cells. Transmission
      electron microscopy revealed multiple epithelial cells with large intranuclear
      aggregates of virions consistent in morphology with papillomavirus.
      Papillomavirus was detected in samples from both turtles by polymerase chain
      reaction (PCR). Sequence analysis of the partial sequence of the papillomavirus
      E1 gene revealed two viruses (CcPV and CmPV) that were distinct from each other
      and from other species in Papillomaviridae, and likely represent two novel
      species and perhaps a new genus.

PMID- 18328646
TI  - Colostrum and milk can transmit jaagsiekte retrovirus to lambs.
AB  - Ovine pulmonary adenocarcinoma (OPA) is a contagious disease caused by jaagsiekte
      sheep retrovirus (JSRV). In the three studies performed, we have obtained data of
      the importance of colostrum/milk (C/M) in the transmission of JSRV. In the first
      study, a group of sheep from a flock with a long history of OPA, samples from
      colostrum and peripheral blood leucocytes (PBLs) were collected. Two specific
      PCRs (U3-LTR and env of the JSRV) were carried out. Using U3PCR 8/34 sheep were
      positive in colostrum whereas with envPCR 7/34 were positive. From these animals
      only one was positive with U3PCR in the PBLs. Evidence of the transmission of
      JSRV infection by C/M was obtained in two more separate studies. In the second
      study, PBLs from five lambs from JSRV+ ewes and two from JSRV-ewes were tested by
      the U3PCR. They were fed C/M by their mothers during 3 months and slaughtered 7
      months after birth. Three out of five lambs from the JSRV+ sheep become PBL
      positive at 3-4 months old and the other two were also positive at 4-6 months of
      age. One lamb of the JSRV-sheep became also PBL positive at an age of 3 months.
      In the third study, a group of lambs from JSRV negative mothers were fed with C/M
      from JSRV+ sheep and housed in separate unit. For comparison, another group of
      the same origin and maintained in another different unit, were fed with C/M
      containing a JSRV virus preparation. All lambs were blood sampled monthly and
      JSRV infection was detected as early as 15 days and several times onwards in both
      groups. Control groups fed with C/M from JSRV free flock and JSRV blood test
      negative sheep were always negative. Together these results indicate that
      suckling is an important natural transmission route for JSRV.

PMID- 18328647
TI  - The plasma angiotensin II level increases in very low-birth weight infants with
      neonatal chronic lung disease.
AB  - BACKGROUND: Angiotensin II (AII) has been reported to play an important role in
      organ fibrosis, and a local renin-angiotensin-system (RAS) has been demonstrated
      in the lungs. However, the relationship of the RAS to chronic lung disease of the
      newborn (CLD) remains obscure. OBJECTIVE: To investigate the plasma AII levels
      throughout the neonatal period in very low-birth weight (VLBW) infants and
      examine the possible factors that might affect the AII levels. STUDY DESIGN: The
      study includes 20 VLBW infants. Blood samples were collected on days 0, 7, 21 and
      35 and plasma AII levels were assayed using an enzyme immunoassay. The data were
      analyzed by a multiple linear regression analysis with the plasma AII level as
      the dependent variable and significant factors determined based on a univariate
      analysis as independent variables. RESULTS: The geometric mean of the plasma AII
      concentrations on days 0, 7, 21 and 35 was 51 pg/mL, 86 pg/mL, 132 pg/mL, and 50
      pg/mL, respectively. On day 21, only CLD (p<0.01) had a highly significant
      association with the plasma AII level. On day 35, birth weight (p<0.05) and CLD
      (p<0.01) had a highly significant association with the plasma AII level. This
      analysis confirmed CLD to be the most significant factor associated with plasma
      AII level on days 21 and 35. CONCLUSION: These findings suggest that higher
      levels of plasma AII in VLBW infants appear to be related to the development of
      CLD.

PMID- 18328648
TI  - Effects of long-term chilled storage of red deer epididymides on DNA integrity
      and motility of thawed spermatozoa.
AB  - We have carried out a study on the influence of prolonged cold storage (5 degrees
      C) of Iberian red deer epididymides on post-thaw sperm motility and DNA
      integrity. Twenty-nine pairs of testes, with attached epididymides, were
      collected during November and December. Spermatozoa from one of each of the pairs
      were immediately recovered, evaluated and frozen (control). The remaining
      epididymides were cooled to 5 degrees C and stored for 24, 96 and 192 h
      (experimental groups), after which spermatozoa were collected and frozen. Samples
      were evaluated before freezing, after thawing, and after a 2-h period of
      incubation at 37 degrees C. Motility was evaluated by means of a CASA system and
      chromatin stability was assessed following the Sperm Chromatin Structure Assay
      (SCSA). Our results showed that, during the first 96 h, the motility (total and
      progressive) did not significantly decline when assessed after cryopreservation,
      although there was a significant decline when epididymides had been stored for
      192 h at 5 degrees C (P<0.001). The present study demonstrates that motility and
      DNA status of thawed spermatozoa collected from refrigerated epididymes, at least
      96 h post-mortem, were good enough to consider their eventual use. Most
      importantly, sperm DNA integrity after thawing was apparently not affected by
      storage time, even after 192 h.

PMID- 18328649
TI  - Estrogen receptor (ER) and ER-related receptor expression in normal and atrophic
      human vagina.
AB  - OBJECTIVES: The estrogen level decline in menopausal status is involved in
      physiological alterations of different human tissues including vaginal mucosa. In
      this study, we have evaluated the estrogen receptor (ER) and estrogen receptor
      related receptor (ERR) expression in tissue samples of posterior vaginal wall
      obtained from pre- and post-menopausal women. METHODS: The nuclear receptor
      expression was determined by quantitative real-time PCR (qPCR). RESULTS: The qPCR
      results showed the presence of the three isoforms of the ERR family (ERRalpha,
      ERRbeta and ERRgamma) that were coexpressed with ERs in all vaginal tissue
      samples examined. The ERRalpha and ERRgamma mRNA levels decreased from normal
      vagina of the pre-menopausal women to atrophic vaginal tissue in post-menopausal
      women. This trend was also observed for the ERbeta subtype. CONCLUSIONS: The
      ERRs, such as ERs, are present in human vagina at the mRNA level and the
      cessation of ovarian estrogen secretion, that is the key event during the post
      menopause, may be linked to ERbeta, ERRalpha and ERRgamma mRNA decline in human
      vaginal mucosa. These findings may provide a biological rationale for the
      clinical susceptibility of the post-menopausal vagina to local estrogen
      treatment.

PMID- 18328650
TI  - Inhalable liposomal formulation for vasoactive intestinal peptide.
AB  - Inhalation of vasoactive intestinal peptide (VIP) was suggested as promising
      treatment option of various lung diseases like asthma and pulmonary hypertension.
      However, the medical use of peptides is limited by their short half-life due to
      rapid enzymatic degradation in the airways. For that reason, we recently
      developed unilamellar nano-sized VIP-loaded liposomes (VLL). Now we investigated
      their applicability for inhalation purposes. After nebulisation by a mouthpiece
      ventilation inhaler we found the particle size almost unaffected, being in a size
      range appropriate for bronchiolar deposition; we observed no peptide release due
      to nebulisation. The VIP release kinetics from VLL were tested by an ex vivo
      vasorelaxation model. Exposure to target organs revealed an immediate response,
      which was significantly retarded for VLL as compared to free VIP (p=0.001). Using
      vasorelaxation as endpoint, we observed a sustained release and an extended
      pharmacological effect compared to equimolar free VIP. The liposomes have the
      potential to improve VIP inhalation therapy by providing a "dispersible peptide
      depot" in the bronchi. Thereby, the release of VIP from liposomes may be
      triggered by exposure to cells, i.e. directly by ligand-receptor interactions.

PMID- 18328651
TI  - The effect of stimulus rate and time-separation on Volterra slices of otoacoustic
      emissions.
AB  - Volterra slices (VSs) of otoacoustic emissions are temporal non-linear
      interaction components which can be measured using the maximum length sequence
      technique of stimulation. Previous studies have found, but not explained, non
      monotonic variations in the amplitude of VSs when stimulus rate is increased. In
      this study, a simple phenomenological model is investigated which provided
      possible insights into the effect of rate on VS amplitudes. Resulting theoretical
      considerations suggest that the effect of rate on VS amplitude is best examined
      when the time-separation parameter of the VS is held constant. To test these
      suggestions, data on VSs of order 2 and 3 were measured in 24 normal hearing ears
      in which the rate is varied while holding constant the time-separation. Under
      these conditions, the results reveal a monotonic reduction in the amplitude of
      the VSs with increasing rate. The phenomenological model offers a possible
      explanation of some of these results in terms of the derivatives of the input
      output function of the non-linearity. In addition, measured cross-correlations
      between waveforms of VS of different order and slice number were obtained,
      revealing a complex dependence on time-separation that has not been explained.

PMID- 18328652
TI  - The comparison of effects of processed Aconiti tuber, U50488H and MK-801 on the
      antinociceptive tolerance to morphine.
AB  - In the previous studies, we demonstrated that an oriental herbal medicine,
      processed Aconiti tuber (PAT), at subanalgesic doses could inhibit or reverse the
      antinociceptive tolerance to morphine. In the present study, we compared the
      effect of PAT, trans-(+/-)-3,4-dichloro-N-methyl-N-(2-(1-pyrrolidin)cyclohexyl)
      benzeneacetamide methane sulfonate hydrate (U50488H), a selective kappa opioid
      receptor (KOR) agonist, and (-)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten
      5,10-imine-maleate (MK-801), a N-methyl-D-aspartate (NMDA) receptor antagonist,
      on the antinociceptive tolerance to morphine in the same experimental condition.
      Mice received subcutaneous morphine (10 mg/kg), and oral PAT at a subanalgesic
      dose (0.3 g/kg for mechanical or 1.0 g/kg for thermal test), or intraperitoneal
      U50488H at a subanalgesic dose (3 mg/kg), or MK-801 at a subanalgesic dose (0.1
      mg/kg) once daily for 14 days. The mechanical nociceptive threshold was measured
      before, and at 60 min by tail pressure testing, and thermal nociceptive latency
      was measured before, and at 30 min by hot plate testing, after daily morphine
      injections. PAT and U50488H could not only inhibit the development of morphine
      tolerance but also reverse the already-developed morphine tolerance, while MK-801
      could only inhibit the development of morphine tolerance but not reverse the
      already-developed morphine tolerance, in both mechanical and thermal nociceptive
      tests. These data suggested that PAT, an indirect-acting KOR agonist, share the
      common pharmacological property of KOR agonists on morphine tolerance, and that
      PAT may be superior to some NMDA receptor antagonists which do not reverse
      already-developed morphine tolerance.

PMID- 18328653
TI  - Middle ear adenoma diagnosed by recurrent facial paralysis.
AB  - Middle ear adenoma is a rare disease derived from the middle ear mucosa. It is
      usually lack specific findings and easily mistaken for other conditions, delaying
      a correct diagnosis. In particular, few cases with facial nerve paralysis have
      been reported. We describe a case of middle ear adenoma that caused hearing loss
      and recurrent facial paralysis in a 29-year-old woman. In an attempt to treat the
      facial nerve paralysis, we performed tympanomastoidectomy and facial nerve
      decompression. By pathological examination, we finally diagnosed it middle ear
      adenoma with neuroendocrine differentiation. Retrospectively, if we meet the
      antibiotic resistant mass in the middle ear, we should suspect the tumor. One
      year after surgery, the adenoma has not recurred but long-term observation is
      required.

PMID- 18328654
TI  - Solitary fibrous tumor in the maxillary sinus treated by endoscopic medial
      maxillectomy.
AB  - Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the
      pleura. Recently, SFTs have been reported in the head and neck area. SFTs of the
      nasal cavity and paranasal sinuses are extremely rare, with only 24 cases
      reported in the English literature. We describe an SFT that arose from the left
      maxillary sinus and extended to the nasal cavity. The tumor was removed by
      endoscopic medial maxillectomy, which permitted monobloc excision of the lesion.
      The patient is without the evidence of the disease 12 months after surgery.

PMID- 18328655
TI  - Atypical motor neuron disease with supranuclear vertical gaze palsy and slow
      saccades.
AB  - In amyotrophic lateral sclerosis (ALS), eye movements are usually preserved even
      after the long-term use of respirators. The present study evaluated a 57-year-old
      male patient who showed clinical findings compatible with ALS but exhibited
      disorders of eye movements before he needed to be on an artificial respiration
      system. The patient had noted clumsiness and weakness in all extremities 5 years
      before presentation of abnormal eye movements. The results of electromyography
      and muscle biopsy were compatible with ALS. However, supranuclear vertical gaze
      palsy and slow saccades are seen. The present case might be representative of a
      distinct clinical entity, motor neuron disease with disorders of eye movement.

PMID- 18328656
TI  - Mechanisms of gastroesophageal reflux in children with sequelae of birth
      asphyxia.
AB  - Patterns of childhood gastroesophageal reflux (GER) have been studied
      extensively; however, the mechanisms underlying its occurrence in neurologically
      impaired children (NIC) are poorly understood. Concurrent esophageal manometry
      and pH monitoring was conducted in 10 un-operated children (7 male; mean age:
      59.5 months) with sequelae birth asphyxia and esophagitis. Reflux episodes were
      scored when esophageal pH decreased to <4 for at least 5 s. When the rate of
      decrease of lower esophageal sphincter (LES) pressure was >1 mmHg/s, the decrease
      of LES pressure was defined as LES relaxation. The time relationship of the
      pharyngeal manometric swallowing signal to LES relaxation onset was then
      evaluated in order to distinguish between LES relaxations associated with
      swallowing (type II or III, associated with one or more swallows, respectively)
      and those that occurred independently of swallowing (type I). RESULTS: Esophageal
      manometry and pH monitoring were conducted for a mean duration of 91.5 min. Basal
      LES pressure averaged (+/-SD) 9.2+/-4.8 mmHg; in 4 of 10 patients (40%) the LES
      pressure was largely undetectable, varying between 0 and 2 mmHg. Mean LES
      pressure was inversely correlated with age (r=0.7, P=0.02). The total number of
      reflux episodes/h averaged 32.1+/-12.1 LES pressure reached 0 mmHg in 98% of
      reflux episodes. Type I LES relaxations were present in 3.15+/-1.1 reflux
      episodes/h, whereas type II LES relaxation occurred in 2.3+/-2.4 episodes/h. Acid
      reflux episodes appeared during absent basal LES tone periods, without phasic LES
      relaxations, in 74%. CONCLUSIONS: Absent basal LES tone is the main mechanism of
      GER in a subgroup of NIC, especially in older children. Transient LES relaxation,
      the most common known event associated with acid reflux in neurologically normal
      children, seems to precede a minority of reflux events in NIC.

PMID- 18328657
TI  - New antiepileptic drugs in pediatric epilepsy.
AB  - New antiepileptic drugs (AEDs), introduced since 1993, provide more diverse
      options in the treatment of epilepsy. Despite the equivalent efficacy and better
      tolerability of these drugs, more than 25% of patients remain refractory to
      treatment. Moreover, the issues for pediatric patients are different from those
      for adults, and have not been addressed in the development and application of the
      new AEDs. Recently published evidence-based treatment guidelines have helped
      physicians to choose the most reasonable AED, although they cannot fully endorse
      new AEDs because of the lack of well-designed, randomized controlled trials. We
      review the mechanisms of action, pharmacokinetic properties, adverse reactions,
      efficacy, and tolerability of eight new AEDs (felbamate, gabapentin, lamotrigine,
      levetiracetam, oxcarbazepine, topiramate, vigabatrin, and zonisamide), focusing
      on currently available treatment guidelines and expert opinions regarding
      pediatric epilepsy.

PMID- 18328658
TI  - Ultrasound-guided biopsy of greater omentum: an effective method to trace the
      origin of unclear ascites.
AB  - OBJECTIVES: Thickened greater omentum is encountered with high frequency in
      patients with ascites. The purpose of our study was to assess the utility of
      greater omentum biopsy under the guidance of ultrasound (US) in tracing the
      origin of unclear ascites and differentiating benign and malignant ascites.
      MATERIALS AND METHODS: We retrospectively reviewed our institutional database for
      all records of greater omentum biopsy cases. One hundred and ninety-four patients
      with unclear ascites and thickened greater omentum were included in the study.
      The sonograms of greater omentum were evaluated before undergoing the ultrasound
      guided biopsy and a biopsy was considered successful if a specific benign or
      malignant diagnosis was rendered by the pathologist. RESULTS: Successful biopsy
      was rendered for 182 biopsy procedures (93.8%, 182/194) including tuberculosis
      (n=114), chronic inflammation (n=3), metastases (n=58), malignant mesothelioma
      (n=6) and pseudomyxoma peritonei (n=1). Twelve biopsies were non-diagnostic.
      According to the results of biopsy and follow-up, the sensitivity and specificity
      of biopsy in distinguishing malignant ascites from benign ascities were
      respectively 95.6% (65/68) and 92.9% (117/126). The greater omentum of 84 cases
      of tuberculous peritonitis showed "cerebral fissure" sign and was well seen as an
      omental cake infiltrated with irregular nodules when involved by carcinomatosis.
      No "cerebral fissure" sign was observed in peritoneal carcinomatosis. The
      sensitivity and specificity of this sign in indicating the existence of
      tuberculous peritonitis were 73.5% (89/121) and 100% (73/73). Moreover, if the
      specific "cerebral fissure" sign was combined with the biopsy results, the
      specificity of biopsy in distinguishing malignant ascites from benign ascits
      increased to 96.8% (122/126). CONCLUSION: Ultrasound-guided biopsy of greater
      omentum is an important and effective method to diagnose the unclear ascites for
      patients with thickened omentum if certain techniques could be paid attention to.
      "Cerebral fissure" sign of greater omentum was a specific sign in indicating the
      tuberculous peritonitis and could increase the specificity of biopsy in
      distinguishing malignant ascites from benign ascits if combined with the biopsy
      results.

PMID- 18328659
TI  - An epidemic outbreak of nephrogenic systemic fibrosis in a Danish hospital.
AB  - The nephrological department of Copenhagen University Hospital Herlev experienced
      an epidemic accumulation of patients developing nephrogenic systemic fibrosis in
      the period 2002-2006. Systematic studies of these patients revealed that they all
      had a gadodiamide-enhanced magnetic resonance examination prior to their
      symptoms, and that they all had severe renal insufficiency (chronic kidney
      disease stage 5) at the time of their exposure to gadodiamide. Besides exposure
      to gadodiamide, our analyses indicated that increasing cumulative gadodiamide
      exposure (i.e. repeated exposures), and higher serum concentrations of ionized
      calcium and phosphate were cofactors that raised the risk of developing
      nephrogenic systemic fibrosis. Higher cumulative gadodiamide exposure, higher
      prescribed erythropoietin dosage at exposure, and being hemodialysis patient were
      three factors associated with nephrogenic systemic fibrosis in its most severe
      form. Retrospective reviews of patients records and patient interviews revealed
      the large variability in symptoms and clinical course of nephrogenic systemic
      fibrosis, but also highlighted that the typical initial symptoms were symmetric
      swelling, discoloration and pain of lower legs, whereas the typical late symptoms
      of severely affected patients were skin thickening, stiffness, contractures, and
      debilitating disabilities. In conclusion, nephrogenic systemic fibrosis is a
      serious iatrogenic disease of patients with renal insufficiency caused by some Gd
      containing contrast agents, in particular gadodiamide. Unfortunately, there is no
      proven curative treatment. It is therefore essential that future cases of
      nephrogenic systemic fibrosis are prevented.

PMID- 18328660
TI  - Posttreatment imaging in head and neck cancer.
AB  - Posttreatment imaging is done when a recurrent tumour is suspected, to confirm
      the presence of such a lesion and to determine its extent. The extent of a
      recurrent cancer is important information for determining the possibility of
      salvage therapy. Imaging may also be used to monitor tumour response and to try
      to detect recurrent or persistent disease before it becomes clinically evident,
      possibly with a better chance for successful salvage. This article reviews the
      expected imaging findings after treatment of head and neck squamous cell cancer,
      and how to differentiate these from persistent or recurrent cancer. The relative
      value of anatomical and biological imaging modalities, including newer techniques
      such as diffusion-weighted magnetic resonance imaging, is addressed. The imaging
      findings in treatment-induced complications, such as tissue necrosis, sometimes
      difficult to differentiate from cancer, are explained.

PMID- 18328661
TI  - Near-infrared reflectance spectroscopy as a process analytical technology tool in
      Ginkgo biloba extract qualification.
AB  - Here, we describe the use of near-infrared diffuse reflectance spectroscopy for
      qualification of Ginkgo biloba extract as raw material for use in pharmaceutical
      products. G. biloba extract shows unpredicted and uncontrolled variability in
      some of its quality specifications, intrinsic to its natural origin, which have
      influence on the manufacturing process of solid dosage forms (viz. granulation
      and compression). Some of these properties could not be determined by
      conventional quality control tests, so we investigated the use of NIR to qualify
      the batches of Ginkgo extract accordingly to its different features and establish
      a relationship with some of the manufacturing steps behaviour based on their
      qualification. Several approaches were evaluated, and the NIR method developed
      demonstrated to be sensitive to changes in important quality specifications and
      therefore adequate to qualify incoming batches of G. biloba extract. This could
      be considered a process analytical technology (PAT) application since it: (1)
      establishes the source of variability in a qualitative way, (2) explains its
      propagation to the final product quality attributes and (3) lays the basis for a
      control strategy to be applied in the manufacturing process.

PMID- 18328662
TI  - The REEME project: a cooperative model for sharing international medical
      education materials.
AB  - Although the Internet has become an excellent source of medical education
      materials, in many specialties, including Emergency Medicine (EM), most of the
      information is in English. Few international EM practitioners can attend costly
      specialty conferences, importing foreign experts to teach at these conferences is
      costly and, even then, these experts are available for a limited time to
      relatively few people. Countries with minimal health care or medical education
      budgets find providing even basic materials for professional medical education
      difficult. An exciting international project now freely distributes Spanish
      language educational programs to health care professionals on topics relating to
      EM. The Recursos Educacionales en Espanol para Medicina de Emergencia (REEME;
      Educational Resources in Spanish for EM) Project (www.reeme.arizona.edu) was
      developed to overcome some of these problems by providing language-specific
      specialty information and widespread international availability, and by promoting
      international cooperation among professional health care educators. It also
      provides a ready source of Spanish medical vocabulary for those trying to learn
      the language. With computer support from the University of Arizona's Learning and
      Technology Center, REEME first went "live" on November 1, 2004. Three years
      later, as of November 1, 2007, the site had 575 programs from 411 donors
      representing 19 countries and the United Nations. There are currently about 645
      downloads per month to users in 73 countries. The REEME Project demonstrates the
      power of the Internet as a means to achieve international cooperation in medical
      education, and can serve as a model for similar projects in other specialties and
      languages.

PMID- 18328663
TI  - Physician counseling for hypertension: what do doctors really do?
AB  - OBJECTIVE: To describe patient counseling by physicians on hypertension and
      lifestyle and assess its impact on participants' satisfaction. METHODS: An
      analysis was conducted of transcripts of audio-recorded outpatient visits,
      augmented with patient and physician surveys. Participants were 30 primary care
      physicians, 11 cardiologists, and 120 hypertensive patients. Each transcript was
      coded into categories descriptive of physicians' counseling behaviors. Patients
      and physicians completed pre- and post-visit questionnaires; patients also
      completed a survey 2 weeks after their visit. RESULTS: Most physicians assessed
      patient medication adherence, but counseling on hypertension and lifestyle was
      limited. Receipt of lifestyle counseling had a positive, short-lived impact on
      patient satisfaction. Physicians reported greater satisfaction with visits
      characterized by more lifestyle counseling. Amount of counseling provided was
      unrelated to the presence of cardiovascular comorbidities. Provision of
      counseling was not associated with physicians' perceptions of visit burden.
      Lifestyle counseling was associated with longer visits. CONCLUSION: Hypertensive
      patients received relatively little information about hypertension and beneficial
      lifestyle changes. PRACTICE IMPLICATIONS: Office visits provide an important
      opportunity for physicians to reinforce key hypertension-related educational
      messages. Physicians could do more to underscore the importance of medication
      adherence and healthy living to their patients with hypertension.

PMID- 18328664
TI  - Internalizing and externalizing behaviors and their association with the
      treatment of adolescents with substance use disorder.
AB  - Whereas the treatment outcome research literature for adolescent alcohol and
      other drug abuse has shown recent advances (R. J. Williams, S. Y. Chang, &
      Addiction Centre Adolescent Research Group, 2000), significant knowledge gaps
      remain. A. E. Kazdin (2001) recently observed that one of the key questions for
      the field is to identify if client characteristics meaningfully mediate or
      moderate treatment outcome. There is support from the adolescent clinical
      literature that internalizing and externalizing personality subtypes are related
      to the onset and course of youth substance use disorders (D. B. Clark & O. G.
      Bukstein, 1998). The study extends this literature by examining the association
      of drug use behaviors outcome and subtyped adolescents (internalizers and
      externalizers; n = 141) who sought treatment at a 12-Step program. The analysis
      also includes a community-based control group (n = 94). Specifically, we examined
      the association of subtype and treatment retention and short-term (Year 1) and
      long-term (Year 4 and Year 5.5) drug involvement outcomes. Externalizers
      consistently showed poorer outcomes, including poorer treatment retention and
      greater drug use and drug disorder symptoms at each follow-up point. The
      treatment implications of the study are discussed.

PMID- 18328665
TI  - Patients with head and neck cancers and associated postirradiated carotid blowout
      syndrome: endovascular therapeutic methods and outcomes.
AB  - PURPOSE: This study retrospectively evaluated the technical and hemostatic
      outcomes of reconstructive and deconstructive endovascular management in patients
      with head and neck cancers associated with carotid blowout syndrome (CBS).
      METHODS: Twenty-four patients with head and neck cancers with CBS involving the
      main trunk of carotid artery underwent endovascular therapy. This included
      reconstructive management with self-expandable stent grafts to preserve the
      diseased carotid artery in 11 patients and deconstructive management with
      balloons, coils, or acrylic adhesives to occlude the diseased carotid artery in
      13 patients. Based on clinical severity and therapeutic priority, we classified
      CBS in our patients into two groups: acute or impending and threatened. The
      angiographic severity was graded from 0 to 3. Evaluation of technical outcome
      included technical success, initial and delayed complications, and patency of
      stent graft in the reconstructive group. The hemostatic outcome was evaluated by
      immediate hemostatic result, rebleeding, and duration of hemostasis. Sex, age,
      clinical and angiographic severities, local wound complications, and location of
      the pathologic lesion were examined as predictors of the technical and hemostatic
      outcomes of endovascular management by using Cox regression method. RESULTS:
      Technical success and immediate hemostasis were achieved in all patients of both
      groups. Initial complications during the procedures were encountered in four
      patients (36.4%) who underwent reconstructive management and in one patient
      (7.7%) who underwent deconstructive management (P = .142). Delayed complications
      during the follow-up were seen in one patient (9.1%) with reconstructive
      management and one patient (7.7%) with deconstructive management (P > .99).
      Rebleeding occurred in five patients (45.5%) in the reconstructive management
      group and in three patients (23.1%) in the deconstructive management group (P =
      .659). The mean duration of hemostasis after initial reconstructive and
      deconstructive management was 4.0 +/- 8.1 and 8.5 +/- 10.1 months, respectively
      (P = .249). Rebleeding was noted in 7 of 11 patients (63.6%) with acute CBS and
      in 1 of 13 patients (7.7%) with impending and threatened CBS (P = .008).
      CONCLUSION: There is no significant difference in technical and hemostatic
      outcomes between the reconstructive and deconstructive endovascular management
      methods. Hemostatic results were influenced by clinical severity. The rebleeding
      rate is higher in patients with advanced and acute clinical severity.

PMID- 18328666
TI  - Midterm outcomes of femoral arteries after percutaneous endovascular aortic
      repair using the Preclose technique.
AB  - OBJECTIVE: Percutaneous access during endovascular aortic repair has been shown
      to be feasible and safe using a suture-mediated closure device ("Preclose"
      technique) for closure of up to 24F introducer sheaths. The purpose of this study
      is to examine the late outcomes of those femoral arteries repaired in this
      manner. METHODS: The Preclose technique has been previously described. Briefly,
      the technique involves two Perclose Proglide devices deployed in the femoral
      artery prior to insertion of the large diameter introducer sheath and then
      closure of the arteriotomy by tying down knots of the Proglide following removal
      of the sheath. The medical records of all patients who underwent endovascular
      aortic repairs using the Preclose technique between December 2004 and August 2007
      were reviewed. Follow-up protocol consisted of computed tomography (CT)
      angiograms performed at 1, 6, and 12 months, and annually thereafter. All
      Preclose patients who had at least a 6-month postoperative scan were included in
      the study. For each patient, the most recent postoperative scan was compared with
      the preoperative scan for evidence of any new anatomic abnormalities of the
      femoral artery such as dissection, stenosis, or pseudoaneurysm. Three-dimensional
      post processing with multiplanar reconstructions was also performed as necessary
      to confirm axial scan findings. RESULTS: A total of 292 patients underwent
      percutaneous endovascular aortic repairs (TEVAR-125, EVAR-167). Four hundred
      thirty-two femoral arteries were closed with 870 devices. Four hundred eighteen
      vessels were approximated with two devices, while 30 arteries required three
      devices for hemostasis and an additional four vessels only required a single
      device. Two hundred seventy-eight (64.3%) vessels were accessed with sheaths 18
      to 24F. Four hundred eight femoral arteries (94.4%) were closed successfully with
      the Preclose technique. There were 100 patients (TEVAR-35, EVAR-65) who had
      adequate postoperative CT scan at 6-months or later. The mean follow up was 11.6
      +/- 5.0 months. Of the 156 femoral arteries in these 100 patients repaired using
      the Preclose technique, there were 3 late complications in 3 patients, 1
      asymptomatic femoral artery dissection, and 2 femoral artery pseudoaneurysms
      requiring surgical repair, resulting in a late complication rate of 1.92%
      (3/156). CONCLUSION: Percutaneous closure of femoral arteries after large
      diameter introducer sheaths using the Preclose technique has a low incidence of
      early and late complications related to the closure site.

PMID- 18328667
TI  - Endogenous heparin activity is decreased in peripheral arterial occlusive
      disease.
AB  - BACKGROUND: Naturally occurring heparin-like activity in the form of endogenous
      heparin and heparin sulfate proteoglycans has been shown in normal human plasma.
      Exogenous low-dose heparin improves pain-free walking distance and maximum
      walking distance in peripheral arterial occlusive disease (PAOD). Is reduced
      endogenous heparin activity responsible for some of the problems found in PAOD?
      This study compared heparin-like activity in patients with PAOD with that in
      healthy subjects and explored its relationship to disease severity. METHODS: In
      part 1, native and heparinase-modified thromboelastography was performed on
      peripheral venous blood samples in three groups of patients to measure heparin
      like anticoagulant activity. Group 1: 15 control subjects (median age, 60 years;
      range, 49-74 years; ankle-brachial pressure index [ABPI] >0.9); group 2: 14
      patients with intermittent claudication (median age, 66 years; range, 56-80;
      ABPI, 0.69 [SD, 0.09]); group 3: 14 patients with rest pain (median age, 67.5
      years; range, 54-84 years; ABPI, 0.45 [SD, 0.08]). In part 2, heparin equivalent
      to that in normal plasma was added to blood samples from 15 patients with short
      distance claudication (n = 4) or rest pain (n = 11), and baseline (without
      heparinase) thromboelastography was performed to exclude lack of antithrombin as
      a cause of diminished heparin-like activity. RESULTS: In part 1, all patients
      with PAOD had a significant increase in coagulability compared with controls.
      Heparinase-modified thromboelastography in controls showed a significant decrease
      in the latent period between placing the sample in the analyser, where it is
      recalcified, to the initial fibrin formation (DeltaR time; P = .002) compared
      with native TEG, confirming endogenous heparin-like activity. Using DeltaR time
      as a measure of heparin-like activity, a significant reduction was found in
      patients with claudication (0.33 minutes; 95% confidence interval [CI], 0.004
      0.65; P = .02) and in those with rest pain (0.25 minutes; 95% CI, -0.02 to 0.52;
      P = .02) compared with that in controls (0.78 minutes; 95% CI, 0.39-1.16). The
      DeltaR time also correlated with the ABPI (r = 0.35, P = .02), suggesting
      declining heparin-like activity with increasing ischemia. In part 2, exogenous
      heparin restored the thromboelastography in PAOD patients to normal, suggesting
      that lack of endogenous heparin-like compounds rather than reduced antithrombin
      levels was responsible for changes in coagulation. CONCLUSION: Patients with PAOD
      have reduced endogenous heparin-like activity that correlates with disease
      severity.

PMID- 18328668
TI  - A 10-year study of outcome following hepatic resection for colorectal liver
      metastases - The effect of evaluation in a multidisciplinary team setting.
AB  - AIMS: Colorectal carcinoma is the second most common cause of cancer death in the
      western world and nearly 50% of patients develop liver metastases. Many cancers
      are managed via a multidisciplinary team process. This study compares the long
      term outcome of patients with metastatic colorectal cancer referred via a
      multidisciplinary team including a liver surgeon (MDT) with those referred
      directly to a specialist hepatobiliary unit. PATIENTS AND METHOD: This is a
      prospective study of 331 consecutive referrals made to a specialist hepatobiliary
      unit over ten years out of which 108 patients were referred via a colorectal MDT
      which included a liver surgeon and 223 were directly referred via colorectal MDTs
      without a liver surgeon. Pre-operative assessment and management were
      standardised and short and long term data were recorded. RESULTS: Patients
      referred via the MDT had 1-, 3- and 5-year survival rates of 89.6%, 67.5% and
      49.9% respectively and 1-, 3- and 5-year disease-free survival of 65.4%, 31% and
      27.2% respectively. Patients referred directly had 1-, 3- and 5-year survival
      rates of 90.3%, 54.1% and 43.3% respectively and 1-, 3- and 5-year disease-free
      survival rates of 70.3%, 37.6% and 27.9% respectively. The difference in overall
      survival was significant (P=0.0001), although the difference in disease-free
      survival was not (P=0.21). CONCLUSION: Assessing, managing and referring patients
      with metastatic colorectal cancer via a multidisciplinary team including a liver
      surgeon is associated with improved overall survival.

PMID- 18328669
TI  - N-Substituted piperazinyl quinolones as potential cytotoxic agents: structure
      activity relationships study.
AB  - As part of a continuing search for new potential anticancer candidates in the
      piperazinyl quinolone series, the cytotoxicity evaluation of new N-substituted
      piperazinyl quinolones was of our interest. The growth inhibitory activities of
      12 new compounds, namely N-[2-(5-chlorothiophen-2-yl)-2-oxoethyl] and N-[2-(5
      chlorothiophen-2-yl)-2-oxyiminoethyl] piperazinyl quinolones 1-12 were determined
      against six cancer cell lines using MTT colorimetric assay. Preliminary screening
      showed that most of the new N-[2-(5-chlorothiophen-2-yl)ethyl]piperazinyl
      quinolones 4-12 containing (un)substituted oxime moiety showed significant
      cytotoxic activity and the modification of functionality on ethyl spacer produced
      a relatively minor change of activity. Thus, in the piperazinyl quinolone series,
      cytotoxic activity can be positively modulated through the introduction of 2-(5
      chlorothiophen-2-yl)ethyl residue on the piperazine ring. The results revealed
      that the introduction of 2-(5-chlorothiophen-2-yl)ethyl moiety on the piperazine
      ring of quinolone antibacterials (ciprofloxacin, norfloxacin and enoxacin)
      changes the biological profile of piperazinyl quinolones from antibacterials to
      cytotoxic agents.

PMID- 18328670
TI  - Iatrogenic agents causing cancer.

PMID- 18328671
TI  - Self-reported symptoms of sleep disturbance and inflammation, coagulation,
      insulin resistance and psychosocial distress: evidence for gender disparity.
AB  - Self-reported ratings of sleep quality and symptoms of poor sleep have been
      linked to increased risk of coronary heart disease (CHD), Type 2 diabetes and
      hypertension with recent evidence suggesting stronger associations in women. At
      this time, the mechanisms of action that underlie these gender-specific
      associations are incompletely defined. The current study examined whether gender
      moderates the relation of subjective sleep and sleep-related symptoms to indices
      of inflammation, coagulation, insulin resistance (IR) and psychosocial distress,
      factors associated with increased risk of cardiovascular and metabolic disorders.
      Subjects were 210 healthy men and women without a history of sleep disorders. The
      Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality and
      frequency of sleep symptoms. In multivariate-adjusted models, overall poor sleep
      quality, more frequent problems falling asleep (>2 night/week) and longer periods
      to fall asleep (>30 min) were associated with greater psychosocial distress,
      higher fasting insulin, fibrinogen and inflammatory biomarkers, but only for
      women. The data suggest that subjective ratings of poor sleep, greater frequency
      of sleep-related symptoms, and longer period of time to fall asleep are
      associated with a mosaic of biobehavioral mechanisms in women and that these
      gender-specific associations have direct implications to recent observations
      suggesting gender differences in the association between symptoms of poor sleep
      and cardiovascular disease.

PMID- 18328672
TI  - The genetics of symptom dimensions of schizophrenia: review and meta-analysis.
AB  - BACKGROUND: The use of symptom dimensions of schizophrenia as quantitative
      phenotypes has been proposed as a mean to reduce the heterogeneity of
      schizophrenia and facilitate genetic research. However, the genetic background of
      symptom dimensions is not clear. AIM: We aim to investigate whether the symptom
      dimensions "reality distortion", "psychomotor poverty" and "disorganization" are
      heritable phenotypes. METHOD: We performed a Medline search including all papers
      from 1980 to August 2007. In addition to reviewing the articles, we performed
      meta-analyses on these studies where possible. RESULTS: We identified 18 relevant
      papers. Only the studies on affected sibling pairs were suitable for meta
      analysis. Data from twin and affected sibling studies are consistent with a
      genetic contribution to the disorganization dimension. However these studies did
      not unequivocally support a large genetic contribution to neither the reality
      distortion symptom dimension nor to the psychomotor poverty symptom dimension. In
      contrast several molecular genetic studies did report associations of genes with
      psychomotor poverty. CONCLUSIONS: These data suggest that only the
      disorganization symptom dimension may provide an useful alternative phenotype for
      genetic research. More research is required to make any definitive conclusions.

PMID- 18328673
TI  - Serum BAFF and APRIL levels in patients with alopecia areata.

PMID- 18328674
TI  - Colistin susceptibility testing by Etest and disk diffusion methods.
AB  - The accuracy of disk susceptibility methods for colistin against 778 bacterial
      pathogens was evaluated in comparison with Etest using interpretive criteria
      available from the Clinical and Laboratory Standards Institute (CLSI). Colistin
      exhibited excellent activity against Acinetobacter baumannii and Escherichia coli
      isolates (minimum inhibitory concentration for 90% of the organisms (MIC(90))=0.5
      mg/L), whilst it was less active both against Enterobacter spp. and Klebsiella
      pneumoniae (MIC for 50% of the organisms (MIC(50))=0.5 mg/L, MIC(90)=16 mg/L).
      Colistin also showed good activity against Pseudomonas aeruginosa (MIC(90)=2
      mg/L, MIC(50)=1 mg/L) but poor activity against Stenotrophomonas maltophilia
      (MIC(50)=8 mg/L, MIC(90)=128 mg/L). Only 0.8% of minor errors were observed
      between the studied methods for P. aeruginosa isolates when the CLSI criteria
      were applied. All A. baumannii isolates with a zone diameter < or =12 mm were
      resistant and those with a zone diameter > or =14 mm were susceptible according
      to MIC breakpoints established by the CLSI. Among nine isolates exhibiting a zone
      diameter of 13 mm, one was resistant to colistin (MIC=8 mg/L) and eight isolates
      were susceptible (MIC=0.5 mg/L). Applying a MIC breakpoint of < or =2 mg/L for
      susceptibility in Enterobacteriaceae, all isolates with a zone diameter > or =14
      mm were susceptible, whilst all isolates with a zone diameter < or =11 mm were
      resistant. Among isolates with zone diameters of 12-13 mm, 59% were characterised
      as susceptible. Major errors were observed only in K. pneumoniae isolates at a
      rate of 0.8%. The poor agar diffusion characteristics of colistin limit the
      predictive accuracy of the disk diffusion test and consequently values of 12-13
      mm should be confirmed with MIC determination by Etest or broth dilution method.

PMID- 18328675
TI  - Change in pain severity with open label venlafaxine use in patients with a
      depressive symptomatology: an observational study in primary care.
AB  - PURPOSE: Venlafaxine has shown benefit in the treatment of depression and pain.
      Worldwide data are extensively lacking investigating the outcome of chronic pain
      patients with depressive symptoms treated by venlafaxine in the primary care
      setting. This observational study aimed to elucidate the efficacy of venlafaxine
      and its prescription by Swiss primary care physicians and psychiatrists in
      patients with chronic pain and depressive symptomatology. SUBJECTS AND METHODS:
      We studied 505 patients with depressive symptoms suffering from chronic pain in a
      prospective naturalistic Swiss community based observational trial with
      venlafaxine in primary care. These patients have been treated with venlafaxine by
      122 physicians, namely psychiatrists, general practitioners, and internists.
      RESULTS: On average, patients were treated with 143+/-75 mg (0-450 mg)
      venlafaxine daily for a follow-up of three months. Venlafaxine proved to be
      beneficial in the treatment of both depressive symptoms and chronic pain.
      DISCUSSION: Although side effects were absent in most patients, physicians might
      have frequently omitted satisfactory response rate of depression by underdosing
      venlafaxine. Our results reflect the complexity in the treatment of chronic pain
      in patients with depressive symptoms in primary care. CONCLUSION: Further
      randomized dose-finding studies are needed to learn more about the appropriate
      dosage in treating depression and comorbid pain with venlafaxine.

PMID- 18328676
TI  - Evidence that the COMTVal158Met polymorphism moderates subclinical psychotic and
      affective symptoms in unaffected first-degree relatives of patients with
      schizophrenia.
AB  - OBJECTIVES: Psychotic patients with COMT(Val158Met) Met alleles were recently
      found to display more intense psychotic and affective responses to daily life
      stressors. We aimed to test the hypothesis that the Met allele is implicated in
      the development of affective and psychotic symptomatology in subjects genetically
      at risk for schizophrenia, by testing if unaffected first-degree relatives of
      patients with schizophrenia who share a Met allele have greater concordance of
      symptomatology than relatives not sharing a Met allele. METHODS: Unaffected
      relatives (n=38) were arranged in as many genetically related pairs as possible
      (n=26), and Met-sharing between Index Unaffected Subject (IUS) and Related
      Unaffected Subject (RUS) was assessed. Symptomatology was assessed with the Brief
      Psychiatric Rating Scale (BPRS) total score. RESULTS: Multilevel regression
      revealed an interaction between RUS BPRS score and Met-sharing in the model of
      IUS BPRS score (interaction chi(2)=3.78, p=0.05). Stratified analyses revealed
      that IUS-RUS total BPRS scores were significantly associated in the case of Met
      sharing (B=0.57, 95% CI: 0.22-0.93, p=0.002), but were not when there was no Met
      sharing. CONCLUSION: These findings support the hypothesis that the Met allele
      may be involved in the causation of psychopathology, at least in populations with
      a genetic predisposition to psychosis.

PMID- 18328677
TI  - Childhood family structure and personality disorders in adulthood.
AB  - BACKGROUND: The association between childhood family structure and
      sociodemographic characteristics and personality disorders (PDs) in a general
      population sample was studied. METHODS: This study is a substudy of the
      prospective Northern Finland 1966 Birth Cohort Project with 1588 young adult
      subjects. The case-finding methods according to the DSM-III-R criteria for PDs
      were: (1) Structured Clinical Interview for DSM-III-R (SCID) for 321 cases who
      participated in a 2-phase field study, (2) Finnish Hospital Discharge Register
      data, and (3) analysis of the patient records in public outpatient care in 1982
      1997. Statistical analyses were performed on the association between PDs and
      family background factors. RESULTS: Altogether 110 (7.0%) of the subjects had at
      least one probable or definite PD. After adjusting for confounders (gender,
      parental social class and parental psychiatric disorder) the results indicated
      that single-parent family type in childhood was associated with cluster B PDs in
      adulthood. Being an only child in childhood was associated with cluster A PDs. No
      special childhood risk factors were found for cluster C PDs. CONCLUSIONS: Results
      suggest that single-parent family type at birth and being an only child in the
      1960s are associated with PD in adulthood. Further studies are needed to explore
      the psychosocial aspects of family environment which may nowadays promote
      vulnerability to PDs in adulthood.

PMID- 18328678
TI  - Identification of presomitic mesoderm (PSM)-specific Mesp1 enhancer and
      generation of a PSM-specific Mesp1/Mesp2-null mouse using BAC-based rescue
      technology.
AB  - Bacterial artificial chromosome (BAC) modification technology is a powerful
      method for the identification of enhancer sequences and genetic modifications.
      Using this method, we have analyzed the Mesp1 and/or Mesp2 enhancers and
      identified P1-PSME, a PSM-specific enhancer of Mesp1, which contains a T-box
      binding site similar to the previously identified P2-PSME. Hence, Mesp1 and Mesp2
      use different enhancers for their PSM-specific expression. In addition, we find
      that these two genes also use distinct enhancers for their early mesodermal
      expression. Based on these results, we generated a PSM-specific Mesp1/Mesp2-null
      mouse by introducing a BAC clone, from which only early mesodermal Mesp1
      expression is possible, into the Mesp1/Mesp2 double knockout (dKO) genetic
      background. This successfully rescued gastrulation defects due to the lack of the
      early mesoderm in the dKO mouse and we thereby obtained a PSM-specific
      Mesp1/Mesp2-null mouse showing a lack of segmented somites.

PMID- 18328679
TI  - Critical micellar concentrations of keto derivatives of selected bile acids:
      thermodynamic functions of micelle formation.
AB  - The knowledge of the process of formation of molecular aggregates of bile acids
      in aqueous media and of the corresponding critical micellar concentrations (CMCs)
      is of great significance because of the biological importance of these compounds
      and their pharmacological applications. In view of this, the present study is
      concerned with the determination of CMCs of cholic and chenodeoxycholic acids and
      their keto derivatives at different temperatures with the aim to calculate the
      standard thermodynamic functions of micelle formation. Based on the molecular
      descriptors for tested compounds and entropy of micelle formation, the method of
      principal component analysis (PCA) allowed grouping of the behavior of tested
      molecules at 30, 50 and 70 degrees C. To one group belong cholic acid and its
      keto derivatives, the other group consisting of chenodeoxycholic and deoxycholic
      acids and their keto derivatives. For each group, the derived multiple linear
      regression equations of the entropy dependence on temperature contains different
      independent variables. A main difference between the two groups of tested bile
      acids is in the energy of dipole-dipole interaction, which appears to be
      temperature dependent, and in the case of the latter group comes into play as an
      independent variable already in the regression equation derived for 30 degrees C.
      The most remarkable changes of the descriptors with temperature were observed in
      the group of cholic acid and its derivatives.

PMID- 18328680
TI  - Coordinated induction of drug transporters and phase I and II metabolism in human
      liver slices.
AB  - Although regulation of phase I drug metabolism in human liver is relatively well
      studied, the regulation of phase II enzymes and of drug transporters is
      incompletely characterized. Therefore, we used human liver slices to investigate
      the PXR, CAR and AhR-mediated induction of drug transporters and phase I and II
      metabolic enzymes. Precision-cut human liver slices were incubated for 5 or 24h
      with prototypical inducers: phenobarbital (PB) (50 microM) for CAR, beta
      naphthoflavone (BNF) (25 microM) for AhR, and rifampicin (RIF) (10 microM) for
      PXR, and gene expression of the phase I enzymes CYP1A1, 1A2, 3A4, 3A5, 2B6, 2A6,
      the phase II enzymes UGT1A1 and 1A6, and the transporters MRP2, MDR1, BSEP, NTCP
      and OATP8 was measured. BNF induced CYP1A1, UGT1A1 and UGT1A6 and MRP2, NTCP and
      MDR1. RIF induced CYP3A4, 3A5, 2B6, 2A6, UGT1A1, UGT1A6 and BSEP, MRP2 and MDR1
      and slightly downregulated OATP8. PB induced CYP3A4, 3A5, 2B6 and 2A6, UGT1A1 and
      all transporters. Large interindividual differences were found with respect to
      the level of induction. Enzyme activity of CYP3A4, measured by testosterone
      metabolism, was increased after 24h by RIF. 7-Ethoxycoumarin O-deethylation
      activity, mediated predominantly by CYP 1A1/1A2 but also by other CYPs, was
      increased after 24h with PB. We have shown that regulation of all phases of the
      (in)activation of a drug via the CAR, AhR and the PXR pathways can be studied in
      human liver slices. The concomitant induction of metabolic enzymes and
      transporters shows that also in the human liver transporters and metabolic
      enzymes are regulated coordinately.

PMID- 18328681
TI  - Genome size, cell size, and the evolution of enucleated erythrocytes in attenuate
      salamanders.
AB  - Within the salamander family Plethodontidae, five different clades have evolved
      high levels of enucleated red blood cells, which are extremely unusual among non
      mammalian vertebrates. In each of these five clades, the salamanders have large
      genomes and miniaturized or attenuated body forms. Such a correlation suggests
      that the loss of nuclei in red blood cells may be related, in part, to the
      interaction between large genome size and small body size, which has been shown
      to have profound morphological consequences for the nervous and visual systems in
      plethodontids. Previous work has demonstrated that variation in both the level of
      enucleated cells and the size of the nuclear genome exists among species of the
      monophyletic plethodontid genus Batrachoseps. Here, we report extensive
      intraspecific variation in levels of enucleated red blood cells in 15 species and
      provide measurements of red blood cell size, nucleus size, and genome size for 13
      species of Batrachoseps. We present a new phylogenetic hypothesis for the genus
      based on 6150bp of mitochondrial DNA sequence data from nine exemplar taxa and
      use it to examine the relationship between genome size and enucleated red blood
      cell morphology in a phylogenetic framework. Our analyses demonstrate positive
      direct correlations between genome size, nucleus size, and both nucleated and
      enucleated cell sizes within Batrachoseps, although only the relationship between
      genome size and nucleus size is significant when phylogenetically independent
      contrasts are used. In light of our results and broader studies of comparative
      hematology, we propose that high levels of enucleated, variably sized red blood
      cells in Batrachoseps may have evolved in response to rheological problems
      associated with the circulation of large red blood cells containing large, bulky
      nuclei in an attenuate organism.

PMID- 18328682
TI  - MMP-9 protein level does not reflect overall MMP activity in the airways of
      patients with COPD.
AB  - BACKGROUND: Animal and human studies have implicated an imbalance of matrix
      metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases
      (TIMPs) in the pathogenesis of chronic obstructive pulmonary disease (COPD). MMP
      9 protein is increased in COPD and we hypothesized that total MMP activity would
      be raised although this has not previously been measured. METHODS: Using
      fluorescence and biotin labelled MMP assays, RT-PCR, western blotting and enzyme
      linked immunosorbent assay we examined total MMP activity, specific gelatinase,
      elastase, collagenase activity, TIMP-1 and TIMP-2 in induced sputum from smokers
      with COPD and smokers without COPD. RESULTS: Induced sputum was obtained from 15
      smokers with COPD and 14 smokers without COPD. MMP-9 levels were higher in those
      with COPD compared with controls (p<0.05). Total MMP activity, specific
      gelatinase, collagenase and elastase activities were not higher in COPD patients.
      In addition, reduced MMP activity was correlated with increasing airflow
      obstruction in COPD (p=0.016). CONCLUSION: MMP-9 protein but not MMP activity was
      higher in sputum of COPD patients compared with controls. These results suggest
      that MMP-9 levels may not reflect the overall MMP activity in the airways of
      patients with COPD suggesting a complex relationship between MMP-9 protein and
      activity. Further studies of MMPs in COPD should comprise activity measures in
      addition to protein levels.

PMID- 18328683
TI  - Does measuring BHR add to guideline derived clinical measures in determining
      treatment for patients with persistent asthma?
AB  - RATIONALE: Little is known about the use of biomarkers in guiding treatment
      decisions in routine asthma management. The objective of this study was to
      determine whether adding a LABA to an ICS would control bronchial
      hyperresponsiveness (BHR) at an overall lower dose of ICS when titration of
      medication was based upon the assessment of routine clinical measures with or
      without the measurement of BHR. METHODS: After a 2-week run-in period, subjects
      (> or = 12 years) were randomized to one of three treatment groups. Two groups
      followed a BHR treatment strategy (based on clinical parameters [lung function,
      asthma symptoms, and bronchodilator use] and BHR) and were treated with either
      fluticasone propionate/salmeterol (FSC(BHR) group) or fluticasone propionate
      (FP(BHR) group) (n=156 each). The third group followed a clinical treatment
      algorithm (based on clinical parameters alone) and were treated with fluticasone
      propionate (FP(REF) group; n=154). All treatments were administered via Diskus.
      Treatment doses were adjusted as needed every 8 weeks for 40 weeks according to
      the subject's derived severity class, which was based on clinical measures of
      asthma control with or without BHR. RESULTS: The mean total daily inhaled
      corticosteroids (ICS) dose during the double-blind treatment period was lower,
      although not statistically significant, in the FSC(BHR) group compared with the
      FP(BHR) group (a difference of -42.9 mcg; p=0.07). Compared with the FP(REF)
      group, the mean total daily ICS dose was higher in the FSC(BHR) group (a
      difference of 85.2 mcg) and was significantly higher in the FP(BHR) group (a
      difference of 131.2 mcg, p=0.037). CONCLUSION: This study demonstrated that for
      most subjects, control of BHR was maintained when treatment was directed toward
      control of clinical parameters. In addition, there was a trend towards control of
      BHR and clinical measures at a lower dose of ICS when used concurrently with
      salmeterol.

PMID- 18328684
TI  - Endothelium-dependent vasorelaxation effect of rutin-free tartary buckwheat
      extract in isolated rat thoracic aorta.
AB  - The aim of this study was to point out the potential of tartary buckwheat on
      vascular functions. A nonabsorbed fraction of hot-water extract of tartary
      buckwheat on a SP70 column (TBSP-T), which was free from rutin, was used for this
      aim. In a contractile experiment using Sprague-Dawley rat thoracic aorta rings
      contracted by 1.0 microM phenylephrine (PE) or 50 mM KCl, TBSP-T evoked a
      significant vasorelaxation [EC50 (mg/ml): PE; 2.2; KCl, 1.9]. By a further
      fractionation of TBSP-T by liquid-liquid partitioning into basic, neutral and
      acidic fractions, a marked enhancement of vasorelaxation effect was observed only
      for acidic fraction (EC50, 0.25 mg/ml). The action of acidic fraction was
      significantly attenuated in endothelium-denuded aortic rings and in the presence
      of nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (100 microM). The
      fraction also enhanced the cyclic guanosine monophosphate (cGMP) production in
      aortic rings contracted with PE [cGMP (pmol/mg protein): PE, 7.2+/-2.3; PE+Acidic
      fraction, 35+/-8]. These results indicate that acidic fraction could mediate
      NO/cGMP pathways, thereby exerting endothelium-dependent vasorelaxation action.
      In conclusion, tartary buckwheat was proven to regulate vascular tones and have
      latent acidic candidates except for rutin.

PMID- 18328685
TI  - Dietary oleic acid and adipocyte lipolytic activity in culture.
AB  - Although various studies have noted fatty-acid-mediated regulation of adipocyte
      lipolysis, determining the isolated effect of a single fatty acid is more
      difficult. We examined the influence of dietary oleic acid on adipose cell
      lipolytic activity and the tissue fat content independently of the variation in
      other dietary fatty acids. We fed 48 rats with six diets designed so that the
      oleic acid content was not correlated with the content of any other fatty acid
      and studied the lipolytic activity and fatty acid content of the tissues. There
      were no differences in the weight of the animals after the diet. The muscle fat
      content and the epinephrine-stimulated lipolytic activity varied significantly
      according to the dietary levels of oleic acid and the tissues, showing a dose
      dependent behavior of the dietary oleic acid concentration. The results of this
      study show that diets rich in oleic acid have a beneficial effect on the
      regulation of lipid metabolism and body weight homeostasis.

PMID- 18328686
TI  - Replacing dietary carbohydrate with protein and fat decreases the concentrations
      of small LDL and the inflammatory response induced by atherogenic diets in the
      guinea pig.

PMID- 18328687
TI  - Effects of soy protein and isoflavone on hepatic fatty acid synthesis and
      oxidation and mRNA expression of uncoupling proteins and peroxisome proliferator
      activated receptor gamma in adipose tissues of rats.
AB  - Soy protein rich in isoflavones profoundly affects lipid metabolism in
      experimental animals. To distinguish the roles of the protein and isoflavone
      components of a soy protein preparation in regulating lipid metabolism, we
      compared the effects of diets containing methanol-washed soy protein low in
      isoflavone supplemented with a 0-, 0.5- and 4-g/kg isoflavone preparation on
      hepatic fatty acid metabolism and adipose tissue gene expression in rats. Diets
      containing soy protein irrespective of the isoflavone levels decreased the
      activities and mRNA expression of enzymes involved in hepatic fatty acid
      synthesis to similar levels. Methanol-washed soy protein compared to casein
      increased the mRNA expression of peroxisome proliferator-activated receptor
      (PPAR) alpha, and supplementing the soy protein diet with isoflavone further
      increased this parameter dose-dependently. However, methanol-washed soy protein
      compared to casein was totally ineffective in altering the activities and mRNA
      levels of enzymes involved in fatty acid oxidation. Supplementation of soy
      protein diets with isoflavone slightly increased these parameters. The mRNA level
      of uncoupling protein (UCP) 1 in brown adipose tissue was significantly increased
      and mRNA levels of UCP2 and 3, and PPARgamma2 tended to be higher in rats fed
      methanol-washed soy protein not supplemented with isoflavone than in the animals
      fed casein. Adding isoflavone to the soy protein diets dose-dependently increased
      these parameters. These results suggested that the protein rather than isoflavone
      component is primarily responsible for the physiological activity of soy protein
      rich in isoflavones in reducing hepatic lipogenesis. However, isoflavones may
      have a role in regulating heptic fatty acid oxidation and adipose tissue gene
      expression.

PMID- 18328688
TI  - Blueberry prevents bone loss in ovariectomized rat model of postmenopausal
      osteoporosis.
AB  - The objective of the present study was to explore the bone protective role of
      blueberry in an ovariectomized rat model. Thirty 6-month-old female Sprague
      Dawley rats were either sham-operated (Sham) or ovariectomized (Ovx) and divided
      into three groups: Sham, Ovx (control), Ovx+blueberry (5% blueberry w/w). After
      100 days of treatment, rats were euthanized, and blood and tissues were
      collected. Bone mineral density (BMD) and content of whole body, right tibia,
      right femur and fourth lumbar vertebra were assessed via dual-energy X-ray
      absorptiometry. As expected, Ovx resulted in loss of whole-body, tibial, femoral,
      and 4th lumbar BMD by approximately 6%. Blueberry treatment was able to prevent
      the loss of whole-body BMD and had an intermediary effect on prevention of tibial
      and femoral BMD when compared to either Sham or Ovx controls. The bone-protective
      effects of blueberry may be due to suppression of Ovx-induced increase in bone
      turnover, as evident by lowered femoral mRNA levels of alkaline phosphatase,
      collagen type I and tartrate-resistant acid phosphatase to the Sham levels.
      Similarly, serum osteocalcein levels were also lower in the blueberry group when
      compared to the Ovx control group, albeit not significantly. In summary, our
      findings indicate that blueberry can prevent bone loss as seen by the increases
      in BMD and favorable changes in biomarkers of bone metabolism.

PMID- 18328689
TI  - Long-term effects of tripeptide Ile-Pro-Pro on osteoblast differentiation in
      vitro.
AB  - Bone mineralization is a result of the function of bone-forming osteoblasts.
      Osteoblast differentiation from their precursors is a carefully controlled
      process that is affected by many signaling molecules. Protein-rich food-derived
      bioactive peptides are reported to express a variety of functions in vivo. We
      studied the long-term in vitro effect of bioactive tripeptide Ile-Pro-Pro (IPP)
      on osteoblasts differentiated from human mesenchymal stem cells. Osteoblast bone
      alkaline phosphatase activity (bALP), bone-forming capacity and gene expression
      were investigated. Treatment with 50 microM IPP had no effect on bALP activity,
      but osteoblast mineralization was increased. Gene expression of beta-catenin,
      Cbfa1/Runx2, PTHrP, CREB-5, osteoglycin, osteocalcin, caspase-8, osteoprotegerin
      (OPG) and RANKL was analyzed by quantitative real-time PCR on Days 13, 17 and 20
      of culture. The results indicate that IPP increased mineral formation due to
      enhanced cell survival and matrix formation. In addition, IPP reduced the
      RANKL/OPG ratio. Bioactive peptides, such as IPP, could be one method by which a
      protein-rich diet promotes bone integrity.

PMID- 18328690
TI  - The structure of protein evolution and the evolution of protein structure.
AB  - The observed distribution of protein structures can give us important clues about
      the underlying evolutionary process, imposing important constraints on possible
      models. The availability of results from an increasing number of genome projects
      has made the development of these models an active area of research. Models
      explaining the observed distribution of structures have focused on the inherent
      functional capabilities and structural properties of different folds and on the
      evolutionary dynamics. Increasingly, these elements are being combined.

PMID- 18328691
TI  - Effects of thyroid hormones on human breast cancer cell proliferation.
AB  - The involvement of estrogens in breast cancer development and growth has been
      well established. However, the effects of thyroid hormones and their combined
      effects with estrogens are not well studied. We investigated the response of
      human breast cancer cells to thyroid hormone, particularly the role of T3 in
      mediating cell proliferation and gene expression. We demonstrated that 17beta
      estradiol (E2) or triiodothyronine (T3) promoted cell proliferation in a dose
      dependent manner in both MCF-7 and T47-D cell lines. The E2- or T3-dependent cell
      proliferation was suppressed by co-administration of the ER antagonist ICI. We
      also demonstrated that T3 could enhance the effect of E2 on cell proliferation in
      T47-D cells. Using an estrogen response element (ERE)-mediated luciferase assay,
      we determined that T3 was able to induce the activation of ERE-mediated gene
      expression in MCF-7 cells, although the effects were much weaker than that
      induced by E2. These results suggest that T3 can promote breast cancer cell
      proliferation and increase the effect of E2 on cell proliferation in some breast
      cancer cell lines and thus that T3 may play a role in breast cancer development
      and progression.

PMID- 18328692
TI  - Adsorption of chromium(III) on lignin.
AB  - In order to assess the possibility of using lignin to remove Cr(III) from waters,
      the adsorption of Cr(III) on lignin isolated from black liquor, a waste product
      of the paper industry, was investigated. The influences of pH, lignin dosage,
      contact time, ionic strength, Cr(III) concentration and other metals were
      investigated. The Cr(III) adsorption was strongly dependent on pH and adsorbent
      dosage, but independent of ionic strength and other metal ions. The adsorption
      kinetic data can be described well with pseudo-second-order model and the
      equilibrium data can be well fitted using Langmuir two-surface model with a
      maximum adsorption capacity of 17.97 mg/g. Cr(III) adsorption on lignin was
      mainly through the ion-exchange mechanism and formed inner-sphere complexes with
      lignin. Successful application in removing Cr(III) was achieved by using a real
      wastewater sample. This study indicates that lignin has the potential to become
      an effective and economical adsorbent for the removal of Cr(III) from
      wastewaters.

PMID- 18328693
TI  - Advance in chitosan hydrolysis by non-specific cellulases.
AB  - Besides the specific chitinase, chitosanase and lysozyme, chitosan also could be
      hydrolyzed by some non-specific enzymes such as cellulase, protease, lipase and
      pepsin, especially cellulase, which show high activity on chitosan. Almost all
      the cellulases produced by different kinds of microorganisms could degrade
      chitosan to chitooligomers. The existence of bifunctional enzymes with cellulase
      and chitosanase activity is one of the reasons for cellulase on chitosan
      hydrolysis. The bifunctional cellulase-chitosanases mainly belong to glycoside
      hydrolase family 8 (GH-8), few belong to GH-5 and GH-7, according to the
      homogeneity analysis of amino acids sequences. Their three dimensional structures
      however have not been clearly determined. This paper may serve as a guide for a
      further study on the relationship between structure and function of
      chitosanolytic cellulases.

PMID- 18328694
TI  - Storing energy crops for methane production: effects of solids content and
      biological additive.
AB  - The effect of storage on chemical characteristics and CH4 yield (taking into
      account loss of VS during storage) of a mixture of grasses and ryegrass, ensiled
      as such (low solids content) and after drying (medium and high solids) with and
      without biological additive, were studied in field and laboratory trials. Up to
      87% and 98% of CH4 yield was preserved with low solids grass (initial TS 15.6%)
      and high solids ryegrass (initial TS 30.4%), respectively, after storage for
      6months, while under suboptimal conditions at most 37% and 52% of CH4 yield were
      lost. Loss in CH4 yield was mainly due to VS loss, presumably caused by secondary
      fermentation as also suggested by increasing pH during storage. Biological
      additive did not assist in preserving the CH4 yield.

PMID- 18328695
TI  - Design and analysis of a solar reactor for anaerobic wastewater treatment.
AB  - The aim of this research was to design a solar heated reactor system to enhance
      the anaerobic treatment of wastewater or biological sludge at temperatures higher
      than the ambient air temperature. For the proposed reactor system, the solar
      energy absorbed by flat plate collectors was transferred to a heat storage tank,
      which continuously supplied an anaerobic-filter reactor with water at a maximum
      temperature of 35 degrees C. The packed reactor was a metallic cylindrical tank
      with a peripheral twin-wall enclosure. Inside this enclosure was circulated warm
      water from the heat storage tank. Furthermore, a mathematical model was developed
      for the prediction of the temperature distribution within the reactor under
      steady state conditions. Preliminary results based on model simulations performed
      with meteorological data from various geographical regions of the world suggested
      that the proposed solar reactor system could be a promising and environmentally
      friendly approach for anaerobic treatment of wastewater and biological sludge.

PMID- 18328696
TI  - Maturity assessment of composted olive mill wastes using UV spectra and
      humification parameters.
AB  - In this study, two olive mill wastes - exhausted olive cake (EOC) and paste of
      olive mill wastewater naturally dehydrated (POMW) - were co-composted and mixed
      with 25% sesame bark (SB). The humification process was evidenced by quantifying
      the humic substances and the generally accepted humification indices: (i) the
      ratio of humic acid (HA) carbon to fulvic acid (FA) carbon (CHA/CFA), (ii) the
      ratio of water soluble organic carbon (CW) to total organic nitrogen (Cw/Norg),
      (iii) and the ratio of humic acid carbon to total organic carbon CHA/Corg and by
      determining the absorbance ratios: E2/E4, E2/E6 and E4/E6. The results showed
      that the time required to reach maturity was dependant on the chemical properties
      of the initial raw materials used. The compost including EOC had more nitrogen
      and synthesised more polymerised HA, the POMW compost also had acceptable degrees
      of stability and maturity at the end of the process. Maturation was confirmed by
      a decline in Cw below 1.7, an increase in nitrogen, in HA, in CHA/CFA and an
      elimination of phytotoxicity. Composts produced with olive mill wastes,
      experimented on potato culture in the field, can be considered beneficial to
      soils because of their humification indexes and no toxicity.

PMID- 18328697
TI  - Decolorization and biosorption for Congo red by system rice hull- Schizophyllum
      sp. F17 under solid-state condition in a continuous flow packed-bed bioreactor.
AB  - Synthetic dyes are important chemical pollutants from various industries. This
      work developed an efficient and relatively simple continuous decolorization
      system rice hull-Schizophyllum sp. F17 under solid-state condition in a packed
      bed bioreactor, for decolorizing Congo red. In the decolorization system, two
      decolorization mechanisms exist, one is decolorization by Schizophyllum sp. F17,
      the other is biosorption by rice hull. The decolorization efficiency was greatly
      affected by dye concentration and hydraulic retention time (HRT), which were
      quantificationally analyzed and optimized through response surface methodology
      (RSM). A 2(2) full factorial central composite design (CCD) was performed, and
      three second order polynomial models were generated to describe the effects of
      dye concentration and HRT on total decolorization (R2=0.902), decolorization by
      Schizophyllum sp. F17 (R2=0.866) and biosorption by rice hull (R2=0.890).
      Response surface contour plots were constructed to show the individual and
      cumulative effects of dye concentration and HRT, and the optimum values. A
      maximum total decolorization 89.71% and maximum decolorization by Schizophyllum
      sp. F17 60.44% was achieved at dye concentration 142.63mg/L, HRT 41h, and dye
      concentration 110.7mg/L, HRT 29.4h, respectively. Meanwhile, the role of
      manganese peroxidase (MnP) in the decolorizaion process was investigated. This
      study proved the feasibility of continuous mode for decolorizing synthetic dyes
      by white-rot fungi in solid-state fermentation bioreactors.

PMID- 18328698
TI  - Enhancement of nitroaromatic compounds anaerobic biotransformation using a novel
      immobilized redox mediator prepared by electropolymerization.
AB  - Functionalized polypyrrole (PPy) composites were prepared by incorporation of a
      model redox mediator, anthraquinonedisulphonate (AQDS), as doping anion during
      the electropolymerization of pyrrole (Py) monomer on active carbon felt (ACF)
      electrode. Then, the resulting composite, ACF/PPy/AQDS as a novel immobilized
      redox mediator for catalyzing anaerobic biotransformation of the model
      nitroaromatic compounds (NACs), such as nitrobenzene (NB), 2,4- and 2,6
      dinitrotoluene (DNT), were investigated in detail. The results showed that
      ACF/PPy/AQDS exhibited good catalytic activity and stability, and its addition
      effectively accelerated the NACs anaerobic reduction to the corresponding amino
      compounds. In order to estimate the relationship between community dynamics and
      the function of immobilized redox mediator, a combined method based on
      fingerprints (ribosomal intergenic spacer analysis, RISA) and 16S rRNA gene
      sequencing was used. The results indicated that the existence of ACF/PPy/AQDS
      made the potent AQDS-reducing bacteria keeping predominant in the catalytic
      systems. Based on the results above, it can be concluded that this novel
      immobilized redox mediator is feasible and potentially useful to enhance NACs
      anaerobic reduction.

PMID- 18328699
TI  - Effect of temperature on performance and microbial diversity in hyperthermophilic
      digester system fed with kitchen garbage.
AB  - The objective of this study was to evaluate the performances and microbial
      diversities for development of the effective hyperthermophilic digester system
      that consists of hyperthermophilic reactor and hyperthermophilic or thermophilic
      reactor in series. Lab-scale reactors were operated continuously fed with
      artificial kitchen garbage. The effect of temperature on the acidification step
      was firstly investigated. Results indicated that 43.1% of COD solubilization was
      achieved at 70 degrees C, while it was about 21% at 80 degrees C. The average
      protein solubilization reached to 31% at 80 degrees C. Methane conversion
      efficiency following the acidification was around 85% in average at 55 degrees C,
      but decreased with increasing temperature and methane gas was not produced over
      73 degrees C. The upper temperature limits for growth of microbes were secondly
      observed and shown to be 73 degrees C for acetate oxidizers, 65 degrees C for
      propionate oxidizers, 70 degrees C for iso-butyrate oxidizers, 80 degrees C for
      lactate oxidizers and 65 degrees C for protein degrading bacteria in the methane
      fermenter. As well as, microbes affiliated with methanogens dominated the
      population below the 65 degrees C, while those affiliated with acidogens were
      predominant over the 73 degrees C. These results indicated that the
      hyperthermophilic processes have considerable benefits to treat wastewater or
      waste containing high concentration of protein.

PMID- 18328700
TI  - Protective effect of nitronyl nitroxide-amino acid conjugates on liver ischemia
      reperfusion induced injury in rats.
AB  - Stable nitroxides are potential antioxidant drugs. In this study, we have linked
      nitroxide to natural amino acids with the aim to improve therapeutic activity.
      The radical scavenging activities of two nitronyl nitroxide-amino acid conjugates
      (NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging
      activities of these compounds were confirmed in the acetylcholine-induced
      vasorelaxation assay. In addition, the protective effect of NNR was demonstrated
      in an in vivo rat model of hepatic ischemia-reperfusion (I/R) induced injury and
      oxidative change. Because NNR reduced hepatic I/R injury by minimizing oxidative
      stress, it might be possible to develop it into a possible therapeutic agent for
      hepatic I/R injury.

PMID- 18328702
TI  - Phase-of-firing coding of natural visual stimuli in primary visual cortex.
AB  - We investigated the hypothesis that neurons encode rich naturalistic stimuli in
      terms of their spike times relative to the phase of ongoing network fluctuations
      rather than only in terms of their spike count. We recorded local field
      potentials (LFPs) and multiunit spikes from the primary visual cortex of
      anaesthetized macaques while binocularly presenting a color movie. We found that
      both the spike counts and the low-frequency LFP phase were reliably modulated by
      the movie and thus conveyed information about it. Moreover, movie periods
      eliciting higher firing rates also elicited a higher reliability of LFP phase
      across trials. To establish whether the LFP phase at which spikes were emitted
      conveyed visual information that could not be extracted by spike rates alone, we
      compared the Shannon information about the movie carried by spike counts to that
      carried by the phase of firing. We found that at low LFP frequencies, the phase
      of firing conveyed 54% additional information beyond that conveyed by spike
      counts. The extra information available in the phase of firing was crucial for
      the disambiguation between stimuli eliciting high spike rates of similar
      magnitude. Thus, phase coding may allow primary cortical neurons to represent
      several effective stimuli in an easily decodable format.

PMID- 18328703
TI  - Response properties of motion-sensitive visual interneurons in the lobula plate
      of Drosophila melanogaster.
AB  - The crystalline-like structure of the optic lobes of the fruit fly Drosophila
      melanogaster has made them a model system for the study of neuronal cell-fate
      determination, axonal path finding, and target selection. For functional studies,
      however, the small size of the constituting visual interneurons has so far
      presented a formidable barrier. We have overcome this problem by establishing in
      vivo whole-cell recordings from genetically targeted visual interneurons of
      Drosophila. Here, we describe the response properties of six motion-sensitive
      large-field neurons in the lobula plate that form a network consisting of
      individually identifiable, directionally selective cells most sensitive to
      vertical image motion (VS cells). Individual VS cell responses to visual motion
      stimuli exhibit all the characteristics that are indicative of presynaptic input
      from elementary motion detectors of the correlation type. Different VS cells
      possess distinct receptive fields that are arranged sequentially along the eye's
      azimuth, corresponding to their characteristic cellular morphology and position
      within the retinotopically organized lobula plate. In addition, lateral
      connections between individual VS cells cause strongly overlapping receptive
      fields that are wider than expected from their dendritic input. Our results
      suggest that motion vision in different dipteran fly species is accomplished in
      similar circuitries and according to common algorithmic rules. The underlying
      neural mechanisms of population coding within the VS cell network and of
      elementary motion detection, respectively, can now be analyzed by the combination
      of electrophysiology and genetic intervention in Drosophila.

PMID- 18328701
TI  - Isolation by distance in the spore-forming soil bacterium Myxococcus xanthus.
AB  - Genetic differentiation between spatially separated populations within a species
      is commonly observed in plants and animals, but its existence in microbes has
      long been a contentious issue. Traditionally, many microbial ecologists have
      reasoned that microbes are not limited by dispersal as a result of their immense
      numbers and microscopic size. In this view, the absence of barriers to gene flow
      between populations would prevent differentiation of populations by genetic drift
      and hinder local adaptation. Myxococcus xanthus is a globally distributed, spore
      forming bacterium that offers a robust test for genetic differentiation among
      populations because sporulation is expected to enhance dispersal. Using multi
      locus sequence data, we show here that both diversity and the degree of
      differentiation between populations increase as a function of distance in M.
      xanthus. Populations are consistently differentiated at scales exceeding 10(2)
      10(3) km, and isolation by distance, the divergence of populations by genetic
      drift due to limited dispersal, is responsible. Our results provide new insights
      into how genetic diversity within species of free-living microbes is distributed
      from centimeter to global scales.

PMID- 18328704
TI  - Impaired synaptic plasticity and motor learning in mice with a point mutation
      implicated in human speech deficits.
AB  - The most well-described example of an inherited speech and language disorder is
      that observed in the multigenerational KE family, caused by a heterozygous
      missense mutation in the FOXP2 gene. Affected individuals are characterized by
      deficits in the learning and production of complex orofacial motor sequences
      underlying fluent speech and display impaired linguistic processing for both
      spoken and written language. The FOXP2 transcription factor is highly similar in
      many vertebrate species, with conserved expression in neural circuits related to
      sensorimotor integration and motor learning. In this study, we generated mice
      carrying an identical point mutation to that of the KE family, yielding the
      equivalent arginine-to-histidine substitution in the Foxp2 DNA-binding domain.
      Homozygous R552H mice show severe reductions in cerebellar growth and postnatal
      weight gain but are able to produce complex innate ultrasonic vocalizations.
      Heterozygous R552H mice are overtly normal in brain structure and development.
      Crucially, although their baseline motor abilities appear to be identical to wild
      type littermates, R552H heterozygotes display significant deficits in species
      typical motor-skill learning, accompanied by abnormal synaptic plasticity in
      striatal and cerebellar neural circuits.

PMID- 18328705
TI  - Visual reliability and information rate in the retina of a nocturnal bee.
AB  - Nocturnal animals relying on vision typically have eyes that are optically and
      morphologically adapted for both increased sensitivity and greater information
      capacity in dim light. Here, we investigate whether adaptations for increased
      sensitivity also are found in their photoreceptors by using closely related and
      fast-flying nocturnal and diurnal bees as model animals. The nocturnal bee
      Megalopta genalis is capable of foraging and homing by using visually
      discriminated landmarks at starlight intensities. Megalopta's near relative,
      Lasioglossum leucozonium, performs these tasks only in bright sunshine. By
      recording intracellular responses to Gaussian white-noise stimuli, we show that
      photoreceptors in Megalopta actually code less information at most light levels
      than those in Lasioglossum. However, as in several other nocturnal arthropods,
      Megalopta's photoreceptors possess a much greater gain of transduction,
      indicating that nocturnal photoreceptors trade information capacity for
      sensitivity. By sacrificing photoreceptor signal-to-noise ratio and information
      capacity in dim light for an increased gain and, thus, an increased sensitivity,
      this strategy can benefit nocturnal insects that use neural summation to improve
      visual reliability at night.

PMID- 18328706
TI  - The octopus vertical lobe modulates short-term learning rate and uses LTP to
      acquire long-term memory.
AB  - Analyzing the processes and neuronal circuitry involved in complex behaviors in
      phylogenetically remote species can help us understand the evolution and function
      of these systems. Cephalopods, with their vertebrate-like behaviors but much
      simpler brains, are ideal for such an analysis. The vertical lobe (VL) of Octopus
      vulgaris is a pivotal brain station in its learning and memory system. To examine
      the organization of the learning and memory circuitry and to test whether the LTP
      that we discovered in the VL is involved in behavioral learning, we tetanized the
      VL to induce a global synaptic enhancement of the VL pathway. The effects of
      tetanization on learning and memory of a passive avoidance task were compared to
      those of transecting the same pathway. Tetanization accelerated and transection
      slowed short-term learning to avoid attacking a negatively reinforced object.
      However, both treatments impaired long-term recall the next day. Our results
      suggest that the learning and memory system in the octopus, as in mammals [9], is
      separated into short- and long-term memory sites. In the octopus, the two memory
      sites are not independent; the VL, which mediates long-term memory acquisition
      through LTP, also modulates the circuitry controlling behavior and short-term
      learning.

PMID- 18328707
TI  - Pom1 DYRK regulates localization of the Rga4 GAP to ensure bipolar activation of
      Cdc42 in fission yeast.
AB  - BACKGROUND: In the fission yeast Schizosaccharomyces pombe, cell growth takes
      place exclusively at both ends of the cylindrical cell. During this highly
      polarized growth, microtubules are responsible for the placement of the cell-end
      marker proteins, the Tea1-Tea4/Wsh3 complex, which recruits the Pom1 DYRK-family
      protein kinase. Pom1 is required for proper positioning of growth sites, and the
      Deltapom1 mutation brings about monopolar cell growth. RESULTS: Pom1 kinase
      physically interacts with Rga4, which has a GAP (GTPase-activating protein)
      domain for Rho-family GTPase. Genetic and biochemical evidence indicates that
      Rga4 functions as GAP for the Cdc42 GTPase, an evolutionarily conserved regulator
      of F-actin. CRIB (Cdc42/Rac interactive binding)-GFP microscopy has revealed that
      GTP-bound, active Cdc42 is concentrated to growing cell ends accompanied by
      developed F-actin structures, where the Rga4 GAP is excluded. The monopolar
      Deltapom1 mutant fails to eliminate Rga4 from the nongrowing cell end, resulting
      in monopolar distribution of GTP-Cdc42 to the growing cell end. However,
      mutational inactivation of Rga4 allows Cdc42 to be active at both ends of
      Deltapom1 cells, suggesting that mislocalization of Rga4 in the Deltapom1 mutant
      contributes to its monopolar phenotype. CONCLUSIONS: Pom1 kinase recruited to
      cell ends by the Tea1-Tea4/Wsh3 complex is essential for proper localization of a
      GAP for Cdc42, Rga4, which ensures bipolar localization of GTP-bound, active
      Cdc42. Because of the established role of Cdc42 in F-actin formation, these
      observations provide a new insight into how the microtubule system achieves
      localized formation of F-actin to generate cell polarity.

PMID- 18328708
TI  - MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation.
AB  - BACKGROUND: MST1 and MST2 are the mammalian Ste20-related protein kinases most
      closely related to Drosophila Hippo, a major regulator of cell proliferation and
      survival during development. Overexpression of MST1 or MST2 in mammalian cells is
      proapototic; however, little is known concerning the physiologic regulation of
      the endogenous MST1/MST2 kinases, their role in mammalian cell proliferation, or
      the identity of the MST1/MST2 substrates critical to proliferative regulation.
      RESULTS: We show that MST1 and MST2 activity increases during mitosis, especially
      in nocodazole-arrested mitotic cells, where these kinases exhibit both an
      increase in both abundance and activation. MST1 and MST2 also can be activated
      nonphysiologically by okadaic acid or H2O2. The MOBKL1A and MOBKL1B polypeptides,
      homologs of the Drosophila MATS polypeptide, are identified as preferred
      MST1/MST2 substrates in vitro and are phosphorylated in cells in an MST1/MST2
      dependent manner in mitosis and in response to okadaic acid or H2O2. MST1/MST2
      catalyzed MOBKL1A/MOBKL1B phosphorylation alters the ability of MOBKL1A/MOBKL1B
      to bind and regulate downstream targets such as the NDR-family protein kinases.
      Thus, MOBKL1A/MOBKL1B phosphorylation in cells promotes MOBKL1A/MOBKL1B binding
      to the LATS1 kinase and enables H2O2-stimulated LATS1 activation loop
      phosphorylation. Most importantly, replacement of endogenous MOBKL1A/MOBKL1B by a
      nonphosphorylatable mutant is sufficient to accelerate cell proliferation
      substantially by speeding progression through G1/S as well as mitotic exit.
      CONCLUSIONS: These results establish that MST1 and MST2 are activated in mitosis
      and catalyze the mitotic phosphorylation of MOBKL1A/MOBKL1B. MOBKL1A/MOBKL1B
      phosphorylation, in turn, is sufficient to inhibit proliferation through actions
      at several points in the cell cycle.

PMID- 18328709
TI  - Regulation of actin cytoskeleton dynamics by Arf-family GTPases.
AB  - Small GTPases of the Arf family are best known for their role in vesicular
      transport, wherein they nucleate the assembly of coat proteins at sites of
      carrier vesicle formation. However, accumulating evidence indicates that the Arfs
      are also important regulators of actin cytoskeleton dynamics and are involved in
      a variety of actin-based processes, including cell adhesion, migration and
      neurite outgrowth. The mechanisms of this regulation are remarkably diverse,
      ranging from the integration of vesicular transport with cytoskeleton assembly to
      the direct regulation of Rho-family GTPase function. Here, we review recent
      progress in our understanding of how Arfs and their interacting proteins function
      to integrate membrane and cytoskeletal dynamics.

PMID- 18328710
TI  - Reliability and validity of the Edinburgh Visual Gait Score for cerebral palsy
      when used by inexperienced observers.
AB  - The Edinburgh Visual Gait Score (EVGS) for cerebral palsy has been validated for
      observer reliability and validity for observers experienced in gait analysis.
      This study investigated the reliability and validity of the EVGS for observers
      inexperienced in gait analysis. Six medical students used the score to analyse
      videotapes from the original study by Read et al. [Read HS, Hazlewood ME, Hillman
      SJ, Prescott RJ, Robb JE. Edinburgh visual gait score for use in cerebral palsy.
      J Pediatr Orthop 2003;23:296-301]. These were viewed on two separate occasions to
      provide inter- and intra-observer reliability, and the results of the numerical
      items were compared to those from three-dimensional (3D) gait analyses for
      validity. Observer agreement was tested using Coefficient of Repeatability (CoR),
      percentage of complete agreement and the kappa statistic. The CoR for inter
      observer agreement for inexperienced observers was 5.99/5.07 (Session 1/Session
      2) compared to 4.60/3.95 (Session 1/Session 2) for experienced observers. The CoR
      for intra-observer agreement for inexperienced observers was 5.15 compared to
      4.21 for experienced observers. There was complete agreement for 52% of the 10
      numerical items with 3D-gait analysis data for inexperienced observers compared
      to 64% for experienced observers. Ranking of reliability of individual items was
      similar between the two groups and was generally best for events occurring at the
      foot and ankle. Observations of gait events by the inexperienced observers using
      the EVGS were reasonably reliable but not very accurate when compared to
      experienced observers and 3D-gait analysis.

PMID- 18328711
TI  - Bacteria from hydrocarbon seep areas growing on   short-chain alkanes.
AB  - Marine hydrocarbon seeps introduce large amounts of organic carbon into the
      environment. Different microorganisms inhabit these unusual environments using
      the hydrocarbons as an energy source. A recent paper by Kniemeyer et al. shows,
      for the first time, that sulfate-reducing bacteria isolated from hydrocarbon
      seeps can oxidize short-chain hydrocarbons anaerobically. This finding is an
      important contribution to our understanding of the role of microbes in the
      recycling of chemically inactive carbon compounds.

PMID- 18328712
TI  - Serum S-100B protein levels in left- and right-hemisphere strokes.
AB  - S-100B is a calcium-binding protein that is expressed in astrocytes. We compared
      the kinetics of serum S-100B in left- and right-hemisphere strokes. Data from 38
      acute ischaemic stroke patients who had serial serum S-100B measurements during
      the first 8 days were analyzed. Stroke severity at baseline, as assessed by the
      National Institutes of Health Stroke Scale (NIHSS), was similar in the two
      groups. Mean S-100B values were greater in the right-hemisphere stroke group at
      all time points. Maximum S-100B levels were low in all patients with lower
      baseline NIHSS scores, and began to rise at a baseline NIHSS score of 16 for
      right-hemisphere stroke and 20 for left-hemisphere stroke. S-100B levels were
      significantly correlated with language in left-hemisphere stroke and with neglect
      in right-hemisphere stroke. These results are consistent with previous
      clinical/radiological findings, suggesting that serum S-100B is brain-specific
      and reflects the extent of brain injury in acute ischaemic stroke.

PMID- 18328713
TI  - Hemichorea, an unusual complication of ventriculoperitoneal shunt.
AB  - We report an unusual case of left hemichorea in a 24-year-old male patient that
      followed the insertion of a right ventriculoperitoneal shunt. This completely
      resolved after removal of the shunt. A review of the available literature and the
      possible aetiopathogenesis is discussed.

PMID- 18328714
TI  - An evaluation of the clinical tests and outcome measures used to assess patellar
      instability.
AB  - A literature review was undertaken to determine which clinical tests and outcome
      measures have been described to diagnose and evaluate patellar instability, and
      to assess the literature examining the sensitivity and specificity of these
      diagnostic tests, or the reliability, validity and responsiveness of the outcome
      measures identified. An electronic search was undertaken using standard databases
      as well as a hand search of specialist journals, reference lists and local
      medical libraries. All English language publications describing and/or evaluating
      diagnostic tests and outcome measures for patellar instability patients were
      included. On review, 104 papers and 64 textbooks were included. Eighteen
      diagnostic tests and 10 outcome measures were identified. Of these only five
      diagnostic tests (Bassett's sign; apprehension test; gravity subluxation test;
      clinical assessment of the tibial tubercle to trochlear groove value; Q-angle)
      and seven outcome measures (modified International Knee Documentation Committee
      knee ligament standard evaluation form; Kujala anterior knee pain scale;
      Fulkerson knee instability scale; Lysholm knee scoring scale; Tegner activity
      level scale; Short Form-36; Musculoskeletal Function Assessment injury and
      arthritis survey) had been assessed for accuracy in five studies. The
      sensitivity, specificity, reliability or validity, of these tests remains unclear
      for this patient population. Further work is needed to assess the appropriateness
      of the identified tests and outcomes for patellar instability cohorts.

PMID- 18328715
TI  - Design and synthesis of nitrate esters of aromatic heterocyclic compounds as
      pharmacological preconditioning agents.
AB  - Ischemic preconditioning (IPC) constitutes an endogenous protective mechanism in
      which one or more brief periods of myocardial ischemia and reperfusion render the
      myocardium resistant to a subsequent more-sustained ischemic insult.
      Pharmacological preconditioning represents an ideal alternative of IPC. We now
      describe the design and synthesis of indole, quinoline, and purine systems with
      an attached pharmacophoric nitrate ester group. The indole and quinoline
      derivatives 4 and 5 possess structural features of the nitrate containing K(ATP)
      channel openers. Purine analogues 11 and 12, substituted at the position 6 by a
      piperidine moiety and at position 9 by an alkyl nitrate, could combine the
      effects of the nitrate containing K(ATP) channel openers and those of adenosine.
      Compound 13 bears the nicotinamide moiety of nicorandil instead of nitrate ester.
      Compounds 4, 5, and 11 reduced infarction and the levels of malondialdehyde (MDA)
      at reperfusion in anesthetized rabbits. Compounds 12 and 13 did not significantly
      reduce the infarct size. Analogues 4 and 5 increased cGMP and MDA during
      ischemia, while combined analogue 4 and mitoK(ATP) blocker 5-hydroxydecanoic acid
      (5-HD) abrogated this benefit suggesting an action through mitoK(ATP) channel
      opening. Treatment with derivative 11 combined with 5-HD as well as treatment
      with 11 and adenosine receptor blocker 8-(p-sulfophenyl)theophylline (SPT) did
      not abrogate cardioprotection. Compound 11 is a lead molecule for the synthesis
      of novel analogues possessing a dual mode of action through cGMP-mitoK(ATP)
      channel opening-free radicals and through adenosine receptors.

PMID- 18328716
TI  - Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana
      L. on rat basophilic leukemia RBL-2H3 cell degranulation.
AB  - Mangostin, Garcinia mangostana L. is used as a traditional medicine in southeast
      Asia for inflammatory and septic ailments. Hitherto we indicated the anticancer
      activity induced by xanthones such as alpha-, beta-, and gamma-mangostin which
      were major constituents of the pericarp of mangosteen fruits. In this study, we
      examined the effect of xanthones on cell degranulation in rat basophilic leukemia
      RBL-2H3 cells. Antigen (Ag)-mediated stimulation of high affinity IgE receptor
      (FcepsilonRI) activates intracellular signal transductions resulting in the
      release of biologically active mediators such as histamine. The release of
      histamine and other inflammatory mediators from mast cell or basophils is the
      primary event in several allergic responses. These xanthones suppressed the
      release of histamine from IgE-sensitized RBL-2H3 cells. In order to reveal the
      inhibitory mechanism of degranulation by xanthones, we examined the activation of
      intracellular signaling molecules such as Lyn, Syk, and PLCgammas. All the
      xanthones tested significantly suppressed the signaling involving Syk and
      PLCgammas. In Ag-mediated activation of FcepsilonRI on mast cells, three major
      subfamilies of mitogen-activated protein kinases were activated. The xanthones
      decreased the level of phospho-ERKs. Furthermore, the levels of phospho-ERKs were
      observed to be regulated by Syk/LAT/Ras/ERK pathway rather than PKC/Raf/ERK
      pathway, suggesting that the inhibitory mechanism of xanthones was mainly due to
      suppression of the Syk/PLCgammas/PKC pathway. Although intracellular free Ca(2+)
      concentration ([Ca(2+)](i)) was elevated by FcepsilonRI activation, it was found
      that alpha- or gamma-mangostin treatment was reduced the [Ca(2+)](i) elevation by
      suppressed Ca(2+) influx.

PMID- 18328717
TI  - A new tool for nanoscale X-ray absorption spectroscopy and element-specific SNOM
      microscopy.
AB  - Investigations of complex nanostructured materials used in modern technologies
      require special experimental techniques able to provide information on the
      structure and electronic properties of materials with a spatial resolution down
      to the nanometer scale. We tried to address these needs through the combination
      of X-ray absorption spectroscopy (XAS) using synchrotron radiation microbeams
      with scanning near-field optical microscopy (SNOM) detection of the X-ray excited
      optical luminescence (XEOL) signal. The first results obtained with the prototype
      instrumentation installed at the European Synchrotron Radiation Facility
      (Grenoble, France) are presented. They illustrate the possibility to detect an
      element-specific contrast and to perform nanoscale XAS experiments at the Zn K
      and W L(3)-absorption edges in pure ZnO and mixed ZnWO(4)/ZnO thin films.

PMID- 18328718
TI  - Structures of human Pumilio with noncognate RNAs reveal molecular mechanisms for
      binding promiscuity.
AB  - Pumilio is a founder member of the evolutionarily conserved Puf family of RNA
      binding proteins that control a number of physiological processes in eukaryotes.
      A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory
      sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains
      in general bind promiscuously to a large set of degenerate sequences, but the
      structural basis for this promiscuity has been unclear. Here, we describe the
      structures of hPum Puf domain complexed to two noncognate RNAs, CycB(reverse) and
      Puf5. In each complex, one of the nucleotides is ejected from the binding
      surface, in effect, acting as a "spacer." The complexes also reveal the
      plasticity of several Puf repeats, which recognize noncanonical nucleotides.
      Together, these complexes provide a molecular basis for recognition of degenerate
      binding sites, which significantly increases the number of mRNAs targeted for
      regulation by Puf proteins in vivo.

PMID- 18328719
TI  - Biotic stress induced demolition of thylakoid structure and loss in photoelectron
      transport of chloroplasts in papaya leaves.
AB  - Papaya mosaic virus (PMV) causes severe mosaic symptoms in the papaya (Carica
      papaya L.) leaves. The PMV-induced alterations in photosystem II (PS II)
      structure and photochemical functions were probed. An increase in chlorophyll a
      (Chl a) fluorescence polarization suggests pathogen-induced transformation of
      thylakoid membrane to a gel phase. This transformation in physical state of
      thylakoid membrane may result in alteration in topology of pigments on pigment
      binding proteins as reflected in pathogen-induced loss in the efficiency of
      energy transfer from carotenoids to chlorophylls. The fast Chl a fluorescence
      induction kinetics of healthy and PMV-infected plants by F(O)-F(J)-F(I)-F(P)
      transients revealed pathogen-induced perturbation on PS II acceptor side electron
      transfer equilibrium between Q(A) and Q(B) and in the pool size of electron
      transport acceptors. Pathogen-induced loss in photosynthetic pigments, changes in
      thylakoid structure and decrease in the ratio of F(V)/F(M) (photochemical
      potential of PS II) further correlate with the loss in photoelectron transport of
      PS II as probed by 2,6-dichlorophenol indophenol (DCPIP)-Hill reaction.
      Restoration of the loss by 1,5-diphenyl carbazide (DPC), an exogenous electron
      donor, that donates electron directly to reaction centre II bypassing the oxygen
      evolving system (OES), leads towards the conclusion that OES is one of the major
      targets of biotic stress. Further, the data suggest that chlorophyll fluorescence
      could be used as a non-invasive handy tool to assess the loss in photosynthetic
      efficiency and symptom severity in infected green tissues vis-a-vis the healthy
      ones.

PMID- 18328720
TI  - Clinical experience with osteosynthesis of subcondylar fractures of the mandible
      using TCP plates.
AB  - AIM: To evaluate the clinical and radiological results obtained with a new kind
      of osteosynthesis device (Modus TCP) plates, Medartis, Basel, Switzerland),
      especially designed for low subcondylar fracture (LSCF) and high subcondylar
      fracture (HSCF) of the mandible in association with the high submandibular
      approach (HSMA). METHOD: A prospective clinical and radiological study was
      carried out over a 41-month period. All adult patients suffering from a displaced
      LSCF or HSCF who consented to the surgical treatment were included in the study.
      All fractures were operated on using an HSMA and were stabilised using a 4- or 9
      hole TCP((R)) plate. No intermaxillary fixation was used and a soft diet was
      started on the 1st postoperative day. Clinical examinations and control X-rays
      were carried out on the 10th postoperative day, in the 1st, the 3rd and, at
      least, in the 6th postoperative months. MATERIAL: Sixty-four patients (12
      females, 52 males - mean age: 28.3) with a total of 75 fractures (54 LSCF, 21
      HSCF) were included in the study. Mean postoperative follow-up was 14 months.
      RESULTS: In the 6th postoperative month, all fractures were consolidated in 79%
      of the cases in an anatomical position. A secondary displacement of the fracture
      occurred in 6.6% of the cases. Plate fracture was not observed. Dental occlusion
      remained unchanged in 94% of the patients. The mandibular movements (mouth
      opening, protrusion, lateral movements on the unfractured and fractured side) had
      normal mean values (49.5, 10.4, 12.8, 12.1mm, respectively). These movements were
      symmetrical in 95% of the patients. No patient complained about articular pain or
      noise. No facial nerve palsy was noticed, not even a transiently one. All
      patients but one found the scars acceptable. CONCLUSION: TCP plates, in
      association with HSMA, were found to be an efficient osteosynthesis device for
      stabilising subcondylar fractures.

PMID- 18328721
TI  - Is post-sternotomy percutaneous dilatational tracheostomy a predictor for sternal
      wound infections?
AB  - OBJECTIVE: Early post-sternotomy tracheostomy is not infrequently considered in
      this era of percutaneous tracheostomy. There is, however, some controversy about
      its association with sternal wound infections. METHODS: Consecutive patients who
      had percutaneous tracheostomy following median sternotomy for cardiac operation
      at our institution from March 1998 through January 2007 were studied, and
      compared to contemporaneous patients. We identified risk factors for
      tracheostomy, and investigated the association between percutaneous tracheostomy
      and deep sternal wound infection (mediastinitis) by multivariate analysis.
      RESULTS: Of 7002 patients, 100 (1.4%) had percutaneous tracheostomy. The
      procedure-specific rates were: 8.6% for aortic surgery, 2.7% for mitral valve
      repair/replacement (MVR), 1.1% for aortic valve replacement (AVR), and 0.9% for
      coronary artery bypass grafting (CABG). Tracheostomy patients differed vastly
      from other patients on account of older age, severe symptoms, preoperative
      support, lower ejection fraction, more comorbidities, more non-elective and
      complex operations and higher EuroScore. Risk factors for tracheostomy were New
      York Heart Association class III/IV (OR 6.01, 95% CI 2.28-16.23, p<0.0001),
      chronic obstructive pulmonary disease (OR 1.84, 95% CI 1.01-3.37, p=0.05),
      preoperative renal failure (OR 3.57, 95% CI 1.41-9.01, p=0.007), prior stroke (OR
      3.08, 95% CI 1.75-5.42, p<0.0001), ejection fraction<0.30% (OR 2.73, 95% CI 1.23
      6.07, p=0.01), and bypass time (OR 1.008, 95% CI 1.004-1.012, p<0.0001). The
      incidences of deep (9% vs 0.7%, p<0.0001) and superficial sternal infections (31%
      vs 6.5%, p<0.0001) were significantly higher among tracheostomy patients.
      Multivariate analysis identified percutaneous tracheostomy as a predictor for
      deep sternal wound infection (OR 3.22, 95% CI 1.14-9.31, p<0.0001). CONCLUSIONS:
      Tracheostomy, often performed in high-risk patients, may further complicate
      recovery with sternal wound infections, including mediastinitis, therefore,
      patients and timing should be carefully selected for post-sternotomy
      tracheostomy.

PMID- 18328722
TI  - Mid-term results after endovascular stent-graft placement due to penetrating
      atherosclerotic ulcers of the thoracic aorta.
AB  - BACKGROUND: To determine mid-term durability of endovascular stent-graft
      placement in patients with penetrating atherosclerotic ulcers (PAU) involving the
      thoracic aorta and to identify risk factors for death as well as early and late
      cardiovascular events. METHODS: From 1997 to 2006, 27 patients (mean age 66 yrs)
      presented with PAU (rupture n=7). Mean numeric EuroScore was 11 and mean logistic
      EuroScore was 35. Median follow-up was 42 (10-86) months, being complete in all
      patients. Outcome variables included death and occurrence of early and late
      cardiovascular events. RESULTS: In-hospital mortality was 11%. Primary success
      rate was 100%. Actuarial survival rates at 1, 3 and 5 years were 93%, 78% and
      70%, respectively. Hemodynamic instability (HR 2.5, 2.1-3.9; p=0.034) as well as
      logistic EuroScore (HR 2.8, 2.4-4.3; p=0.019) was identified as independent
      predictor of early and late cardiovascular events. CONCLUSIONS: Endovascular
      stent-graft placement in patients with PAU is an effective palliation for a life
      threatening sign of a severe systemic process. Hemodynamic instability at
      referral and a high preoperative risk score predict adverse outcome. During mid
      term follow-up, patients are mainly limited by sequelae of their underlying
      disease.

PMID- 18328723
TI  - Redo aortic root surgery for failure of an aortic homograft is a major technical
      challenge.
AB  - OBJECTIVE: Aortic homografts offer many advantages over prosthetic valves.
      However, homograft dysfunction due to degeneration or infection may lead to
      reoperation. Aortic valve replacement in patients who have undergone previous
      aortic root replacement with an aortic homograft remains a technical challenge.
      To assess reoperation events a retrospective review was conducted. MATERIALS AND
      METHODS: From January 2000 to October 2006, 20 consecutive patients (38.8+/-14.9
      years old) underwent repeat surgery for aortic homograft failure. RESULTS:
      Reoperation was performed 7.2+/-3.5 years after implantation of the aortic
      homograft as a root. Indication was homograft degeneration (n=18 [90%]) and
      endocarditis (n=2 [10%]). In patients with major homograft wall calcifications or
      endocarditis, nine aortic root reconstructions were performed (Bentall procedure
      n=7; homograft implantation n=2). Each homograft was dissected with electrical
      cauterization and removed 'en-bloc' sparing the coronary buttons. In case of
      flexible homograft wall, stented prostheses (mechanical n=10, bioprosthesis n=1)
      were implanted along the homograft annulus. Additional procedures consisted of
      mitral valve replacements (n=8), tricuspid repairs (n=4), Konno procedure (n=1)
      and coronary bypass (n=5). Perioperative complications occurred in seven (35%)
      patients: sternal re-entry accident (n=2); reoperations for mediastinitis (n=1)
      or bleeding (n=2); renal insufficiency (n=1); total heart block (n=1). No
      association was found between operative procedures and postoperative
      complications (Fisher's exact test). Two patients (10%) died from multiorgan
      failure in the early postoperative period. In total, 94.4% of the survivors
      remained free from reoperation at 74 months. CONCLUSION: Reoperation on patients
      with an aortic homograft as a root presents a relatively high perioperative
      morbidity. The surgical strategy depends on the degree of homograft wall
      calcification.

PMID- 18328724
TI  - Peripheral tissue metabolism during off-pump versus on-pump coronary artery
      bypass graft surgery: the microdialysis study.
AB  - OBJECTIVE: The aim of this study was to monitor and compare metabolic changes in
      the skeletal muscle during coronary artery bypass grafting surgery with and
      without cardiopulmonary bypass (CPB) by means of interstitial microdialysis.
      Glucose, lactate, pyruvate and glycerol were assessed as markers of basic
      metabolism and tissue perfusion. METHODS: Twenty patients undergoing surgical
      myocardial revascularization were enrolled in this pilot study. Ten patients were
      operated on without CPB (group A, off-pump) and 10 patients using normothermic
      CPB (group B, on-pump). Interstitial microdialysis was performed by a CMA 60
      (CMA/Microdialysis AB, Sweden) probe, inserted into the patient's left deltoid
      muscle. Microdialysis measurements were performed at 30 min intervals. Glucose,
      lactate, pyruvate and glycerol were measured in samples using a CMA 600 Analyser
      (CMA/Microdialysis AB, Sweden). Results in both groups were statistically
      processed and the groups were compared. RESULTS: Both groups were similar with
      regards to preoperative characteristics. Dynamic changes of interstitial
      concentrations of the measured analytes were found in off-pump (group A) and on
      pump (group B) patients during the operation. There were no significant
      differences in dialysate concentrations of glucose and lactate between the
      groups. Significant differences were detected in pyruvate concentrations, lactate
      pyruvate ratio and glycerol concentrations between off-pump versus on-pump
      patients. Pyruvate concentrations were higher in the off-pump group (p<0.05), the
      lactate-pyruvate ratios indicating the aerobic/anaerobic metabolism status were
      lower in the off-pump group (p<0.01) and the values of the concentrations of
      glycerol were lower in the off-pump group (p<0.01). CONCLUSION: Dynamic changes
      in the interstitial concentrations of the glucose, glycerol, pyruvate and lactate
      were found in both groups of patients (off-pump and on-pump). The presented
      preliminary results suggest that extracorporeal circulation during cardiac
      operations could compromise skeletal muscle energy metabolism.

PMID- 18328726
TI  - The decision to operate: role of integrated computed tomography positron emission
      tomography in staging oesophageal and oesophagogastric junction cancer by the
      multidisciplinary team.
AB  - OBJECTIVE: Our objective was to assess the role of fusion positron emission
      tomography-computed tomography (PET-CT) in staging patients for minimally
      invasive oesophagectomy (MIO) with potentially resectable disease from the
      perspective of a multidisciplinary team (MDT) deciding on operability with
      conventional staging investigations. METHODS: Fifty consecutive patients
      presenting with potentially operable oesophageal or oesophagogastric junctional
      tumours were staged with computed tomography (CT) and endoluminal ultrasound
      (EUS). The MDT categorised patients as group A (n=33; CT N0M0) or group B (n=17;
      CT N1/possible M1). All patients underwent FDG PET-CT. Patients with localised
      disease (at T3), including single level N1 disease on PET-CT, were deemed
      suitable for induction chemotherapy followed by surgery. RESULTS: PET-CT re
      categorised 12% of patients as inoperable on grounds of distant metastases (four
      in group A, two in group B). Five patients did not proceed to resection for other
      reasons. Two had metastatic disease at thoracoscopy. Resection specimens (n=37)
      contained 24 nodes (median). Compared with pN status, positive predictive value
      of PET-CT was 40% and negative predictive value was 43%. The expected PET-CT N1
      group had the highest mean number of involved nodes. Median survival for all
      patients (n=50) was 31.9 months for group A compared with 17.3 months for group B
      (not statistically significant). There was no significant difference between
      patients who were PET-CT N0 or N1 in survival or disease-free survival in
      patients undergoing surgery (n=37). CONCLUSIONS: PET-CT informs the MDT decision
      to operate in avoiding futile surgery in stage IV disease or widespread nodal
      disease. In this study, overall PET-CT N1 status has low positive and negative
      predictive value for overall pN status.

PMID- 18328727
TI  - Predictive adaptive responses in perspective.

PMID- 18328728
TI  - Identification of dimethyldioctadecylammonium ion (m/z 550.6) and related species
      (m/z 522.6, 494.6) as a source of contamination in mass spectrometry.
AB  - Chemical contamination can be one of the more common problems encountered when
      performing trace-level analysis regardless of the analytical technique.
      Minimizing or eliminating background interferences can be a difficult task, so
      knowledge of the chemical composition of these contaminants can prove invaluable
      when it comes to identifying the source. Once the source is identified, proper
      steps may be taken to reduce or eliminate it. In this study, we report the
      identity of some commonly seen contaminants (m/z 550.6, 522.6, and 494.6) in
      electrospray ionization (ESI) mass spectrometry (MS). Through MS, tandem MS,
      accurate-mass, and high-resolution measurements we have identified these
      background contaminants as being quaternary ammonium species that contain long
      chain hydrocarbon groups, where m/z 550.6 is a dimethyldioctadecylammonium ion
      (C(18), C(18)) and m/z 522.6 and 494.6 are similar in nature but have shorter
      alkyl-chain groups. The lipophilic nature of these compounds and the fact that
      they have molecular weights similar to lysophospholipids make them a frequent
      contaminant in lipidomic studies. The likely sources of these compounds are
      commonly used personal and household products.

PMID- 18328729
TI  - Escherichia coli expression and purification of four antimicrobial peptides fused
      to a family 3 carbohydrate-binding module (CBM) from Clostridium thermocellum.
AB  - Antimicrobial peptides (AMPs) are molecules that act in a wide range of
      physiological defensive mechanisms developed to counteract bacteria, fungi,
      parasites and viruses. Several hundreds of AMPs have been identified and
      characterized. These molecules are presently gaining increasing importance, as a
      consequence of their remarkable resistance to microorganism adaptation.
      Carbohydrate-binding modules (CBMs) are non-catalytic domains that anchor
      glycoside hydrolases into complex carbohydrates. Clostridium thermocellum
      produces a multi-enzyme complex of cellulases and hemicellulases, termed the
      cellulosome, which is organized by the scaffoldin protein CipA. Binding of the
      cellulosome to the plant cell wall results from the action of CipA family 3 CBM
      (CBM3), which presents a high affinity for crystalline cellulose. Here CipA
      family 3 CBM was fused to four different AMPs using recombinant DNA technology
      and the fusion recombinant proteins were expressed at high levels in Escherichia
      coli cells. CBM3 does not present antibacterial activity and does not bind to the
      bacterial surface. However, the four recombinant proteins retained the ability to
      bind cellulose, suggesting that CBM3 is a good candidate polypeptide to direct
      the binding of AMPs into cellulosic supports. A comprehensive characterization of
      the antimicrobial activity of the recombinant fusion proteins is currently under
      evaluation.

PMID- 18328730
TI  - Forming nacreous layer of the shells of the bivalves Atrina rigida and Pinctada
      margaritifera: an environmental- and cryo-scanning electron microscopy study.
AB  - A key to understanding control over mineral formation in mollusk shells is the
      microenvironment inside the pre-formed 3-dimensional organic matrix framework
      where mineral forms. Much of what is known about nacre formation is from
      observations of the mature tissue. Although these studies have elucidated several
      important aspects of this process, the structure of the organic matrix and the
      microenvironment where the crystal nucleates and grows are very difficult to
      infer from observations of the mature nacre. Here, we use environmental- and cryo
      scanning electron microscopy to investigate the organic matrix structure at the
      onset of mineralization in the nacre of two mollusk species: the bivalves Atrina
      rigida and Pinctada margaritifera. These two techniques allow the visualization
      of hydrated biological materials coupled with the preservation of the organic
      matrix close to physiological conditions. We identified a hydrated gel-like
      protein phase filling the space between two interlamellar sheets prior to mineral
      formation. The results are consistent with this phase being the silk-like
      proteins, and show that mineral formation does not occur in an aqueous solution,
      but in a hydrated gel-like medium. As the tablets grow, the silk-fibroin is
      pushed aside and becomes sandwiched between the mineral and the chitin layer.

PMID- 18328731
TI  - Formation and oral administration of alginate microspheres loaded with pDNA
      coding for lymphocystis disease virus (LCDV) to Japanese flounder.
AB  - Oral delivery of plasmid DNA (pDNA) is a desirable approach for fish immunization
      in intensive culture. However, its effectiveness is limited because of possible
      degradation of pDNA in the fish's digestive system. In this report, alginate
      microspheres loaded with pDNA coding for fish lymphocystis disease virus (LCDV)
      and green fluorescent protein were prepared with a modified oil containing water
      (W/O) emulsification method. Yield, loading percent and encapsulation efficiency
      of alginate microspheres were 90.5%, 1.8% and 92.7%, respectively. The alginate
      microspheres had diameters of less than 10 microm, and their shape was spherical.
      As compared to sodium alginate, a remarkable increase of DNA-phosphodiester and
      DNA-phosphomonoester bonds was observed for alginate microspheres loaded with
      pDNA by Fourier transform infrared (FTIR) spectroscopic analysis. Agarose gel
      electrophoresis showed a little supercoiled pDNA was transformed to open circular
      and linear pDNA during encapsulation. The cumulative release of pDNA in alginate
      microspheres was <or=10% in pH 2.0 acidic media, and it was less than 6.5% in pH
      9.0 alkaline media in 12h. RT-PCR and immunofluorescence imaging indicated that
      pDNA expressed RNA and green fluorescent protein in tissues of fish 10-90 days
      after oral administration. An indirect enzyme-linked immunosorbent assay (ELISA)
      showed that sera were positive (OD >or=0.3) for anti-LCDV antibody from week 3 to
      week 16 for fish orally vaccinated with alginate microspheres loaded with pDNA,
      in comparison with fish orally vaccinated with naked pDNA. Our results display
      that alginate microspheres obtained by W/O emulsification are promising carriers
      for oral delivery of pDNA. This encapsulation technique has the potential for DNA
      vaccine delivery applications due to its ease of operation, low cost and
      significant immune effect.

PMID- 18328732
TI  - Manganese enhanced MRI detects mossy fiber sprouting rather than
      neurodegeneration, gliosis or seizure-activity in the epileptic rat hippocampus.
AB  - We tested a hypothesis that manganese enhanced magnetic resonance imaging (MEMRI)
      after systemic injection of MnCl(2) could detect axonal sprouting in the
      hippocampus following kainate (KA) induced status epilepticus (SE). MEMRI was
      performed at 3 h, 25 h, 4 days, and 2 months post-SE. To assess the contribution
      of various cellular alterations that occur in parallel with sprouting to the
      MEMRI signal, we sacrificed animals for histology at 4 days and 2 months post-SE.
      Neurodegeneration was assessed from thionin and Fluoro-Jade B stained
      preparations, astrogliosis from GFAP (glial fibrillary acidic protein) and
      microgliosis from Ox-42 immunostained preparations. Sprouting of granule cells
      axons (mossy fibers) in the dentate gyrus was analyzed from Timm stained
      sections. Occurrence of spontaneous epileptic seizures was analyzed at 2 months
      post-SE using continuous video-EEG monitoring. Integrity of the blood-brain
      barrier (BBB) was studied using Gd-enhanced MRI. We found abnormal MEMRI
      hyperintensity in the CA1 and the dentate gyrus at 2 months post-SE but not at
      earlier time points. Based on histologic analysis of individual animals with
      MEMRI hyperintensity, hippocampal MEMRI changes could be attributed to increasing
      axonal density rather than to neurodegeneration, astrogliosis, or microgliosis.
      Moreover, MEMRI contrast was not affected by seizure activity, and we could not
      detect any leakage of the BBB that could have explained the observed MEMRI
      hyperintensity. Present data show that systemic MEMRI can reveal axonal
      sprouting, and thus, can potentially serve as a marker for neuroplasticity in
      preclinical studies.

PMID- 18328733
TI  - Voxelwise Bayesian lesion-deficit analysis.
AB  - Relating cognitive deficits to the presence of lesions has been an important
      means of delineating structure-function associations in the human brain. We
      propose a voxel-based Bayesian method for lesion-deficit analysis, which
      identifies complex linear or nonlinear associations among brain-lesion locations,
      and neurological status. We validated this method using a simulated data set, and
      we applied this algorithm to data obtained from an acute-stroke study to identify
      associations among voxels with infarct or hypoperfusion, and impaired word
      reading. We found that a distributed region involving Brodmann areas (BA) 22, 37,
      39, and 40 was implicated in word reading.

PMID- 18328734
TI  - High similarity at three MHC loci between the baiji and finless porpoise: trans
      species or convergent evolution?
AB  - Two DRA alleles and six MHC-I alleles were identified from a group of 15 baiji
      (Lipotes vexillifer), the most threatened cetacean in the world. Little sequence
      variation was detected at the DRA locus but extensive variation at the MHC-I
      locus. In combination with data at the DQB locus previously reported, three MHC
      loci exon 2 of the baiji all revealed striking similarity with those of the
      finless porpoise. Especially, some identical alleles shared by both species at
      the MHC-I and DQB loci suggested the convergent evolution as a consequence of
      common adaptive solutions to similar environmental pressures in the Yangtze
      River. As for DRA locus, the identity alleles were shared not only by baiji and
      finless porpoise but by some other cetacean species of the families Phocoenidae
      and Delphinidae, suggesting trans-species evolution on this gene.

PMID- 18328735
TI  - Combined analysis of fourteen nuclear genes refines the Ursidae phylogeny.
AB  - Despite numerous studies, questions remain about the evolutionary history of
      Ursidae and additional independent genetic markers were needed to elucidate these
      ambiguities. For this purpose, we sequenced ten nuclear genes for all the eight
      extant bear species. By combining these new sequences with those of four other
      recently published nuclear markers, we provide new insights into the phylogenetic
      relationships of the Ursidae family members. The hypothesis that the giant panda
      was the first species to diverge among ursids is definitively confirmed and the
      precise branching order within the Ursus genus is clarified for the first time.
      Moreover, our analyses indicate that the American and the Asiatic black bears do
      not cluster as sister taxa, as had been previously hypothesised. Sun and sloth
      bears clearly appear as the most basal ursine species but uncertainties about
      their exact relationships remain. Since our larger dataset did not enable us to
      clarify this last question, identifying rare genomic changes in bear genomes
      could be a promising solution for further studies.

PMID- 18328736
TI  - A timescale and phylogeny for "bandicoots" (Peramelemorphia: Marsupialia) based
      on sequences for five nuclear genes.
AB  - Relationships among the living and recently extinct genera of bandicoots
      (Marsupialia: Peramelemorphia) have proven difficult to discern. Previous
      phylogenetic studies have used only morphology or mitochondrial DNA and have
      reported conflicting results in regards to their relationships. Most phylogenetic
      reconstructions recognize a basal split between the bilby Macrotis
      (Thylacomyidae) and the Peramelidae. The Peramelidae is composed of the
      Peramelinae (Isoodon and Perameles), Echymiperinae (Echymipera and
      Microperoryctes), and Peroryctinae (Peroryctes). Within Peramelidae, Echymipera
      and Microperoryctes usually group together to the exclusion of Peroryctes. This
      clade is sister to the Peramelinae. Placement of the recently extinct pig-footed
      bandicoot (Chaeropus: Chaeropodidae) has been ambiguous. We address the
      interrelationships and estimate times of divergence for the living bandicoot
      genera using a 6 kilobase concatenation consisting of protein-coding regions of
      five nuclear genes (ApoB, BRCA1, IRBP, Rag1, and vWF). We analyzed this
      concatenation using maximum parsimony, maximum likelihood, and Bayesian methods
      and estimated times of divergence using two Bayesian relaxed molecular clock
      methods. In all concatenated analyses, all nodes associated with the
      Peramelemorphia were robustly supported (bootstrap support percentages=100;
      posterior probabilities=1.00). Macrotis was recovered as basal to the remaining
      living bandicoots. Within the Peramelidae, Echymipera and Microperoryctes grouped
      to the exclusion of Peroryctes and this clade was sister to the Peramelinae. Only
      Rag1 amplified for Chaeropus; analyses based on this gene provide moderate
      support for an association of Chaeropus plus Peramelidae to the exclusion of
      Macrotis. Both relaxed clock Bayesian methods suggest that the living bandicoots
      are a relatively recent radiation originating sometime in the late Oligocene or
      early Miocene with subsequent radiations in the late Miocene to early Pliocene.

PMID- 18328737
TI  - Molecular systematics and evolution in an African cycad-weevil interaction:
      Amorphocerini (Coleoptera: Curculionidae: Molytinae) weevils on Encephalartos.
AB  - Weevils in the tribe Amorphocerini have been implicated in pollination of
      Encephalartos species in southern Africa. The services they render these plants
      and the unique attributes of the cycad-weevil interaction make them important
      from both conservation and evolutionary standpoints. Oberprieler [Oberprieler,
      R.G., 1996. Systematics and evolution of the tribe Amorphocerini, with a review
      of the cycad weevils of the world. Ph.D. dissertation, University of the Free
      State, Bloemfontein, South Africa], using morphological characters, proposed a
      tentative hypothesis of relationships among the Amorphocerini which is tested
      here using DNA sequence data. Sequences from one mitochondrial and three nuclear
      genes were used to infer phylogenetic relationships, levels of sequence
      divergence, evolution of host associations, and patterns of speciation in this
      tribe. The results are reasonably consistent with the morphological hypothesis of
      relationships and species concepts, though important differences are observed,
      particularly in relationships among a Porthetes hispidus Boheman species group,
      which is indicated to have experienced recent divergences. In general, low levels
      of sequence divergence among species within two of the three genera indicate a
      recent radiation of this tribe onto African cycads, thus while cycad-insect
      interactions have often been considered ancient this may not be the case for some
      extant interactions. A complex pattern of host shifts onto both closely related
      and more distantly related hosts is suggested.

PMID- 18328738
TI  - Arthroscopic glenohumeral folds and microscopic glenohumeral ligaments: the
      fasciculus obliquus is the missing link.
AB  - This study tested the hypotheses that the folds in the inferior glenohumeral
      capsule appear at the borders and crossings of the underlying capsular ligaments
      and that embalming may result in misinterpretation of these folds as ligaments.
      The inferior capsular structures in 80 unembalmed cadaver shoulders were compared
      with 24 embalmed shoulders. During arthroscopy and dissection, an anteroinferior
      fold was more prominently seen in internal rotation and was almost obliterated in
      external rotation. A posteroinferior fold appeared in external rotation and
      almost disappeared in internal rotation. During dissection, the anteroinferior
      fold developed at the border of the anterior band of the inferior glenohumeral
      ligament (ABIGHL) and where this ligament crossed with the fasciculus obliquus
      (FO). Several patterns of crossing of the ABIGHL and the FO were seen that
      determined the folding-unfolding mechanism of the anteroinferior fold and the
      appearance of possible synovial recesses. The axillary part of the IGHL is formed
      by the FO on the glenoid side and by the ABIGHL on the humeral side. The
      posteroinferior fold was determined by the posterior band of the IGHL. The folds
      in the embalmed specimens did not necessarily correspond with the underlying
      fibrous structure of the capsule. The folds and recesses observed during
      arthroscopy indicate the underlying capsular ligaments but are not the ligaments
      themselves. The IGHL complex is formed by its anterior and posterior bands and
      also by the FO. Both findings are important during shoulder instability
      procedures because the ligaments need to be restored to their appropriate anatomy
      and tension. Because the FO may also be involved, Bankart-type surgery may have
      to reach far inferiorly. Midsubstance capsular shift procedures also need to
      incorporate this ligament.

PMID- 18328739
TI  - In vitro and finite element analysis of glenoid bone/baseplate interaction in the
      reverse shoulder design.
AB  - We developed biomechanical and finite element models, using high-strength
      polyurethane foam blocks, to represent the glenoid bone/baseplate junction to
      determine if increasing the distance between the glenoid bone and the center of
      rotation of the glenosphere increases baseplate motion during static loading in
      the reverse shoulder design. Although there was a general trend toward increased
      baseplate motion with increasing distance from the glenoid to the center of
      rotation, in vitro mechanical testing revealed no significant difference between
      the 7 glenosphere types tested, with average baseplate motion during 1000 load
      cycles ranging from 90 mum to 120 mum. Results from the finite element analysis
      strongly correlated with the in vitro mechanical testing. The magnitude of
      baseplate motion occurring in a modeled representation of bone under simulated
      physiologic loading conditions was similar for the 7 reverse shoulder glenoid
      components tested in this study.

PMID- 18328740
TI  - Pulsed radiofrequency applied to the suprascapular nerve in painful cuff tear
      arthropathy.
AB  - The purpose of this study was to assess the efficacy of pulsed radiofrequency
      (PRF) applied to the suprascapular nerve for pain relief in medically unfit
      patients with painful cuff tear arthropathy. Twelve patients with chronic
      shoulder pain due to cuff tear arthropathy were recruited. The mean age was 68
      years (range, 60-83 years). The suprascapular nerve was targeted at the
      suprascapular notch with PRF. The patients were assessed with the Oxford score,
      Constant score, and visual analog scale (VAS) pain score before ablation and 3
      and 6 months after ablation. Statistical analysis was undertaken by use of the
      Friedman test. Ten patients showed improvement in the VAS score (P = .24) and
      Constant score (P = .005) and eleven in the Oxford score (P = .001). There was a
      deterioration in the VAS scores between 3 and 6 months, suggesting that the
      benefits were starting to wear off with time (P > .05). We conclude that PRF may
      be a useful therapeutic adjunct in patients with painful, end-stage rotator cuff
      tear arthropathy who are medically unfit for surgery.

PMID- 18328741
TI  - Normal glenoid vault anatomy and validation of a novel glenoid implant shape.
AB  - Current glenoid implants are designed to be secured to the articular surface.
      When the articular surface is compromised, a glenoid component could be implanted
      if it obtained fixation from the endosteal surface of the glenoid vault. The
      first step for designing such a glenoid implant is to define the normal three
      dimensional anatomy of the glenoid vault. The purpose of this study was to define
      the variations in glenoid vault shape in a large group of cadaver scapula.
      Computed tomographic (CT) scans of 61 normal scapulae (mean, 25-34 years) from
      the Haman-Todd Osteological Collection, with a wide range of sizes, were examined
      to define the normal glenoid vault anatomy. A custom software program was used to
      manipulate and measure the scans to determine the morphologic variations among
      the different glenoid vaults. From these data, we defined a unique glenoid vault
      shape and empirically developed 5 sizes to represent the study population of the
      61 scapulae. A second group of 11 cadaver scapulae were used to validate the
      shape defined using the other 61. Prototype implants were placed into the real 11
      scapulae using standard surgical techniques and then CT-scanned to analyze the
      shape of the glenoid vault. In the 61 scapulae, 85% of the points defining the
      endosteal surfaces vary among scapulae by less than 2 mm. For each of the 11
      cadaver scapulae, the implant size used in the virtual computer implantation was
      the same size used for the plastic components placed into the cadaver scapulae.
      Fifty percent of the measured distances between the outer dimensions of the
      plastic models was within 2.4 mm of the glenoid endosteal surface. Eighty percent
      of the surface area of the plastic models was within 3.1 mm of the glenoid
      endosteal surface. Five percent of the dimensions were less than 1 mm and were
      considered to be areas of point contact. Before designing implants that can be
      used in pathologic glenoids, the shape of the normal glenoid vault must first be
      defined. This study defined a normal glenoid vault shape that can accommodate
      different sized scapula with 5 sizes. This glenoid shape may be used as a
      template to design a glenoid implant that obtains fixation within the glenoid
      vault.

PMID- 18328742
TI  - Locally produced complement fragments C5a and C3a provide both costimulatory and
      survival signals to naive CD4+ T cells.
AB  - Costimulatory signals are critical to T cell activation, but how their effects
      are mediated remains incompletely characterized. Here, we demonstrate that
      locally produced C5a and C3a anaphylatoxins interacting with their G protein
      coupled receptors (GPCRs), C5aR and C3aR, on APCs and T cells both upstream and
      downstream of CD28 and CD40L signaling are integrally involved in T cell
      proliferation and differentiation. Disabling these interactions reduced MHC class
      II and costimulatory-molecule expression and dramatically diminished T cell
      responses. Importantly, impaired T cell activation by Cd80-/-Cd86-/- and Cd40-/-
      APCs was reconstituted by added C5a or C3a. C5aR and C3aR mediated their effects
      via PI-3 kinase-gamma-dependent AKT phosphorylation, providing a link between
      GPCR signaling, CD28 costimulation, and T cell survival. These local paracrine
      and autocrine interactions thus operate constitutively in naive T cells to
      maintain viability, and their amplification by cognate APC partners thus is
      critical to T cell costimulation.

PMID- 18328743
TI  - Neuropilin-1 expression on regulatory T cells enhances their interactions with
      dendritic cells during antigen recognition.
AB  - The interaction of T cells with dendritic cells (DCs) determines whether an
      immune response is launched or not. Recognition of antigen leads to formation of
      immunological synapses at the interface between the cells. The length of
      interaction is likely to determine the functional outcome, because it limits the
      number of MHC class II-peptide complexes that can be recruited into the synapse.
      Here, we show that regulatory T (Treg) cells and naive helper T (Th) cells
      interact differently with DCs in the absence of proinflammatory stimuli. Although
      differences in T cell receptor repertoire might contribute, Foxp3-induced
      phenotypic differences play a major role. We found that Neuropilin-1 (Nrp-1),
      which is expressed by most Treg cells but not naive Th cells, promoted prolonged
      interactions with immature DCs (iDCs), resulting in higher sensitivity to
      limiting amounts of antigen. This is likely to give Treg cells an advantage over
      naive Th cells, with the same specificity leading to a "default" suppression of
      immune responses in the absence of "danger signals."

PMID- 18328744
TI  - Mutations in growth factor independent-1 associated with human neutropenia block
      murine granulopoiesis through colony stimulating factor-1.
AB  - Severe congenital neutropenia (SCN) is characterized by a deficiency of mature
      neutrophils, leading to recurrent bacterial and fungal infections. Although
      mutations in Elastase-2, neutrophil (ELA2) predominate in human SCN, mutation of
      Ela2 in mice does not recapitulate SCN. The growth factor independent-1 (GFI1)
      transcription factor regulates ELA2. Mutations in GFI1 are associated with human
      SCN, and genetic deletion of Gfi1 results in murine neutropenia. We examined
      whether human SCN-associated GFI1N382S mutant proteins are causal in SCN and
      found that GFI1 functions as a rate-limiting granulopoietic molecular switch. The
      N382S mutation inhibited GFI1 DNA binding and resulted in a dominant-negative
      block to murine granulopoiesis. Moreover, Gfi1N382S selectively derepressed the
      monopoietic cytokine CSF1 and its receptor. Gfi1N382S-expressing Csf1-/- cells
      formed neutrophils. These results reveal a common transcriptional program that
      underlies both human and murine myelopoiesis, and that is central to the
      pathogenesis of SCN associated with mutations in GFI1. This shared
      transcriptional pathway may provide new avenues for understanding SCN caused by
      mutations in other genes and for clinical intervention into human neutropenias.

PMID- 18328745
TI  - Letter to the Editor re: identifying the carotid 'high risk' plaque.

PMID- 18328746
TI  - Left-right asymmetry in Drosophila.
AB  - Seminal studies of left-right (L/R) patterning in vertebrate models have led to
      the discovery of roles for the nodal pathway, ion flows and cilia in this
      process. Although the molecular mechanisms underlying L/R asymmetries seen in
      protostomes are less well understood, recent work using Drosophila melanogaster
      as a novel genetic model system to study this process has identified a number of
      mutations affecting directional organ looping. The genetic analysis of this, the
      most evolutionary conserved feature of L/R patterning, revealed the existence of
      a L/R pathway that involves the actin cytoskeleton and an associated type I
      myosin. In this review, we describe this work in the context of Drosophila
      development, and discuss the implications of these results for our understanding
      of L/R patterning in general.

PMID- 18328747
TI  - Asymmetric stem cell division: lessons from Drosophila.
AB  - Asymmetric cell division is an important and conserved strategy in the generation
      of cellular diversity during animal development. Many of our insights into the
      underlying mechanisms of asymmetric cell division have been gained from
      Drosophila, including the establishment of polarity, orientation of mitotic
      spindles and segregation of cell fate determinants. Recent studies are also
      beginning to reveal the connection between the misregulation of asymmetric cell
      division and cancer. What we are learning from Drosophila as a model system has
      implication both for stem cell biology and also cancer research.

PMID- 18328748
TI  - A semi-defined medium without serum for small ruminant mycoplasmas.
AB  - The composition of the medium used to cultivate Mycoplasma species is very
      important. Serum is one of the most important additives as it contains lipids
      (cholesterol) and serum proteins, which are essential for the growth of the
      organisms. This work reports the development of a semi-defined medium, called MWS
      (Medium Without Serum) produced without animal serum and bovine serum albumin.
      MWS seems to be suitable for cultivating several species of caprine mycoplasma,
      especially M. mycoides subsp. mycoides (LC) and M. mycoides subsp. capri.

PMID- 18328749
TI  - Postpartum uterine disease and dairy herd reproductive performance: a review.
AB  - This paper reviews the causes, impact, treatment, and prevention of retained
      placenta (RP), metritis, and endometritis in dairy cows. The occurrence of each
      of these diseases largely depends on immune function in the transition period.
      Retained placenta affects 5-10% of calvings and greatly increases the risk of
      metritis and endometritis. More field studies are needed to validate criteria for
      treatment of metritis, but cows with at least two of RP, fever, dullness, and
      fetid uterine discharge appear to merit treatment with systemic antibiotics.
      Clinical endometritis affects 15-20% of cows at 4-6 weeks postpartum; an
      additional 30-35% have subclinical endometritis between 4 and 9 weeks postpartum.
      Under specific conditions, treatment of cows with endometritis improved pregnancy
      rate. Systematic use of prostaglandin F(2alpha) at 5 and 7 weeks postpartum may
      improve pregnancy rate. The economic benefit of efforts to identify and treat
      endometritis is herd-specific.

PMID- 18328750
TI  - Prevalence and risk factors for dystocia in dairy cattle: a review.
AB  - This review focuses on the case definition of dystocia, its current prevalence
      and recent temporal trends, the different types of dystocia and their associated
      risk factors in dairy cattle. The reported dystocia rates in dairy cattle
      internationally are generally <5%, apart from those in the United States, where
      they are higher. Given the skewed distribution of herd dystocia rates, average
      figures mask high prevalence herds. Phenotypic dystocia trends are generally
      increasing internationally and this trend has been partially attributed to the
      introduction of Holstein genes. The principal types of dystocia differ between
      primiparae and pluriparae, with feto-pelvic disproportion (FPD) predominating in
      the former and fetal malposition in the latter. In order of importance, the two
      major determinants of FPD are calf birthweight and maternal pelvic size. Abnormal
      fetal position is most influenced by the number of fetuses, parity and calf sire
      breed. Adequate weighting of dystocia in selection indices, achievement of heifer
      rearing targets prior to both service and calving, and appropriate periparturient
      management decisions are prerequisites for controlling dystocia in dairy cattle.

PMID- 18328751
TI  - Subacute ruminal acidosis (SARA) in grazing Irish dairy cows.
AB  - Subacute ruminal acidosis (SARA) is a significant production disease of dairy
      cattle. Previous concerns have been raised over the occurrence of SARA in pasture
      fed dairy cattle and the potential consequences of laminitis and lameness. Highly
      digestible perennial rye grass contains high concentrations of rapidly
      fermentable carbohydrate and low concentrations of physical effective fibre that
      may result in SARA. This study conducted a point prevalence survey of rumen
      health status in grazing Irish dairy cattle fed predominantly perennial rye grass
      based pasture. The survey assessed rumen fluid, animal health status, milk
      production data and pasture composition. A total of 144 cows between 80 and 150
      days in milk were sampled on 12 farms. Eleven percent of cows were classified as
      affected with SARA (pH < or = 5.5), 42% were marginal (pH 5.6-5.8) and 47% were
      normal (pH>5.8). The study showed that low rumen pH is prevalent in grazing Irish
      dairy cattle consuming perennial rye grass-based pasture and raises concerns
      regarding effective pasture utilisation and possible consequences for animal
      health.

PMID- 18328752
TI  - Quantitative somatic sensory testing and functional imaging of the response to
      painful stimuli before and after cingulotomy for obsessive-compulsive disorder
      (OCD).
AB  - The middle cingulate cortex (MCC) has been implicated in pain processing by
      studies of cingulotomy for chronic pain and imaging studies documenting increased
      MCC blood flow in response to acute pain. The only previous report of
      quantitative sensory testing following cingulotomy described increased intensity
      and unpleasantness ratings of painful hot and cold stimuli in a single patient
      with psychiatric disease. We now report a case in which perception of pain and
      temperature was assessed before and after cingulotomy for obsessive-compulsive
      disorder (OCD). Positron emission tomographic (PET) studies of the blood flow
      response to acute pain were carried out using a single subject design which
      allowed for statistical evaluation of postoperative blood flow changes in this
      case. Postoperatively, the patient demonstrated increased intensity and
      unpleasantness ratings of painful thermal waterbath stimuli. The PET studies
      demonstrated preoperative contact heat pain-evoked activation of the bilateral
      MCC/SMA (supplementary motor area) and the left (contralateral) fronto-parietal
      operculum. Postoperative pain-evoked activation was demonstrated in the right
      (ipsilateral) parasylvian cortex but not of the MCC/SMA. Prior studies of
      forebrain lesions, and of cortical synchrony during the application of painful
      stimuli suggest the presence of functional connectivity between components of the
      MCC/SMA and the fronto-parietal opercula. Therefore present results suggest that
      cingulate lesions disinhibit ipsilateral parasylvian cortex and so are
      independent evidence of functional connectivity between these cortical areas, the
      defining characteristic of modules in a pain network.

PMID- 18328753
TI  - Parallel MRI at microtesla fields.
AB  - Parallel imaging techniques have been widely used in high-field magnetic
      resonance imaging (MRI). Multiple receiver coils have been shown to improve image
      quality and allow accelerated image acquisition. Magnetic resonance imaging at
      ultra-low fields (ULF MRI) is a new imaging approach that uses SQUID
      (superconducting quantum interference device) sensors to measure the spatially
      encoded precession of pre-polarized nuclear spin populations at microtesla-range
      measurement fields. In this work, parallel imaging at microtesla fields is
      systematically studied for the first time. A seven-channel SQUID system, designed
      for both ULF MRI and magnetoencephalography (MEG), is used to acquire 3D images
      of a human hand, as well as 2D images of a large water phantom. The imaging is
      performed at 46 mu T measurement field with pre-polarization at 40 mT. It is
      shown how the use of seven channels increases imaging field of view and improves
      signal-to-noise ratio for the hand images. A simple procedure for approximate
      correction of concomitant gradient artifacts is described. Noise propagation is
      analyzed experimentally, and the main source of correlated noise is identified.
      Accelerated imaging based on one-dimensional undersampling and 1D SENSE
      (sensitivity encoding) image reconstruction is studied in the case of the 2D
      phantom. Actual threefold imaging acceleration in comparison to single-average
      fully encoded Fourier imaging is demonstrated. These results show that parallel
      imaging methods are efficient in ULF MRI, and that imaging performance of SQUID
      based instruments improves substantially as the number of channels is increased.

PMID- 18328754
TI  - The importance of the domain of applicability in QSAR modeling.
AB  - The domain of applicability is an important concept in quantitative structure
      activity relationships (QSAR) that allows one to estimate the uncertainty in the
      prediction of a particular molecule based on how similar it is to the compounds
      used to build the model. In this paper we discuss this important concept,
      providing details of the development and application of a method to compute the
      domain of applicability within model descriptor space and structural space as
      defined by daylight fingerprints. The importance of the domain of applicability
      is illustrated using five QSAR models generated on plasma protein binding and
      P450 inhibition datasets. Such methodologies will be shown to offer us a means to
      monitor the performance of QSARs over time, providing us both with a way to
      estimate the accuracy of a given prediction and identify when a model needs to be
      rebuilt.

PMID- 18328755
TI  - Structural, electronic, and magnetic properties of heterofullerene C(58)Si with
      odd number of atoms and a near planar tetracoordinate Si atom.
AB  - Density functional calculations and minimization techniques have been employed to
      characterize the structural and electronic properties of [5,6]-heterofullerene
      C(58)Si-C(2v). Since it has odd number of atoms and a near planar tetracoordinate
      Si atom on the skeleton of the cage, it has odd number of atoms assembling a cage
      and is a novel molecule. Vibrational frequencies of the molecule have been
      calculated at the B3LYP/6-31G* level of theory. The absence of imaginary
      vibrational frequency confirms that the molecule corresponds to a true minimum on
      the potential energy hypersurface. Sixteen (13)C nuclear magnetic resonance (NMR)
      spectral signals of C(58)Si are characterized, and its heat of formation was
      estimated in this work.

PMID- 18328756
TI  - Melatonin and its possible role in mediating seasonal metabolic changes of
      Antarctic krill, Euphausia superba.
AB  - Melatonin, the chief secretory product of the vertebrate pineal gland is
      suspected to be a ubiquitous molecule principally involved in the transduction of
      photoperiodic information. Besides vertebrates, melatonin has been detected
      throughout phylogeny in numerous non-vertebrate taxa. In the present study, the
      occurrence of melatonin in Antarctic krill Euphausia superba and its possible
      role in mediating seasonal metabolic changes was evaluated. Melatonin was
      quantified by enzyme linked immunosorbent assay (ELISA) in high performance
      liquid chromatography (HPLC) purified extracts of eyestalks and hemolymph of
      krill sampled in the Lazarev Sea during the Antarctic winter and summer. In
      addition, oxygen uptake rates and the activities of the metabolic enzyme malate
      dehydrogenase (MDH) were recorded to assess the metabolic status of krill.
      Validation of melatonin measurements was carried out on the basis of three
      different extraction methods with parallel determination of melatonin by ELISA in
      crude extracts and in HPLC purified extracts, and after derivatization of
      melatonin under alkaline conditions in the presence of hydrogen peroxide. A
      significantly higher respiration rate and MDH activity was found in summer krill
      than in winter krill indicating that krill was in a state of reduced metabolic
      activity during winter. However, neither during winter nor during summer there
      were detectable melatonin concentrations in the visual system or hemolymph of
      krill. Based on these results, we question a mediating role of melatonin in the
      control of seasonal metabolic changes in Antarctic krill.

PMID- 18328757
TI  - Effect of starvation and refeeding on digestive enzyme activities in sturgeon
      (Acipenser naccarii) and trout (Oncorhynchus mykiss).
AB  - The digestive enzyme activities were determined in Adriatic sturgeon and rainbow
      trout during starvation and refeeding period. Overall, the digestive enzyme
      activities are affected in the same sense in both species. The protease and
      lipase activities were decreased later than amylase activity. Even after 1 month
      of starvation, both species would be prepared to digest protein and lipids in an
      effective way. After 72 days of starvation, the digestive machinery of the
      sturgeon and of the trout shows an altered capacity to digest macronutrients. The
      capacity to digest proteins and lipids, after 60 days of refeeding, begins to
      become re-established in sturgeon and trout. In contrast, in this period, the
      capacity to digest carbohydrates remains depressed in both species.

PMID- 18328758
TI  - Occurrence of pancreatic lipase-related protein-2 in various species and its
      relationship with herbivore diet.
AB  - The occurrence of classical pancreatic lipase (PL) and pancreatic lipase-related
      proteins 1 and 2 (PLRP1s and 2) in the pancreas of ten mammalian species (humans,
      pig, rat, guinea pig, coypu, rabbit, horse, ox, goat and sheep) and two bird
      species (ostrich and turkey) was investigated. The lipases were purified from
      delipidated pancreas and identified based on the results of Western blotting
      analysis with anti-human PLRP2 serum, the catalytic properties and N-terminal
      microsequencing data. PLRP2s were detected in the pancreas of monogastric
      herbivorous animals (guinea pig, coypu, rabbit and horse) but not in that of
      ruminant herbivorous animals (ox, goat and sheep). The pancreas of carnivorous
      animals (dogs and cats) does not have any detectable PLRP2, but contains high
      levels of PL and PLRP1. By contrast, the pancreas of omnivorous animals (humans
      and rats) contains PL, PLRP1 and PLRP2, with the exception of porcine pancreas,
      where no PLRP2 was detected. In the case of bird (ostrich and turkey) pancreases,
      only classical PL was detected. The substrate specificity of PLRP2s was
      investigated using phospholipid micelles and synthetic monomolecular galactolipid
      films. Like human PLRP2, rabbit and horse PLRP2s are galactolipases. In
      polygastric herbivorous animals (ruminants), however, galactolipids are
      hydrolyzed via microbial enzymatic processes (involving galactolipases). The
      absence of galactolipids in carnivorous animals' diet may explain why no PLRP2s
      were detected here in the pancreas of these species.

PMID- 18328759
TI  - A role for plasmin in platelet aggregation: differential regulation of IGF
      release from IGF-IGFBP complexes?
AB  - OBJECTIVES: To determine if plasmin differentially augments platelet aggregation
      through variable efficiencies of IGF-IGFBP complex cleavage. METHODS: We utilized
      ADP-triggered platelet aggregation assays to test the effects of IGF-I versus IGF
      II in complex with IGFBP-2 or IGFBP-3 upon the efficiency of plasmin (a known
      IGFBP protease) as a pro-aggregatory stimulus. In vitro proteolysis assays were
      performed as controls. RESULTS: We found that IGF-I complexes augmented platelet
      mediated aggregation whereas IGF-II either had no effect (IGFBP-2) or inhibited
      platelet-mediated aggregation (IGFBP-3). In vitro proteolysis assays of IGFBP-2
      and IGFBP-3 using plasmin revealed that three of the four aggregation findings
      were explained by the disparate efficiencies of IGFBP proteolysis associated with
      each IGF. Only IGF-II-IGFBP-2 complex resulted in a finding that could not be
      explained by the concept of differential regulation of plasmin's proteolysis
      efficiency by the two IGF ligands. CONCLUSIONS: Our findings demonstrate that the
      plasmin can differentially modulate platelet aggregation in response to intrinsic
      heterogeneities within the IGF axis.

PMID- 18328760
TI  - The promise of nuclear medicine technology: status and future perspective of high
      resolution whole-body PET.
AB  - Positron emission tomography has rapidly emerged over the past 50+ years
      resulting in highly sophisticated tools for medical diagnosis. However, spatial
      resolution is still one of the drawbacks of PET. Modern whole-body PET devices
      provide a spatial resolution in the range of 4-6mm FWHM. Physical constraints are
      equally responsible for limited spatial resolution as factors caused by
      geometrical effects or by detector crystal properties. This paper focuses on the
      question why it is still a major challenge--despite the invention of new crystals
      and readout electronics--to build a high-resolution whole-body PET system for
      humans. Physical constraints are discussed and possible solutions for high
      resolution PET are presented.

PMID- 18328761
TI  - Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro
      inflammatory response in macrophages through release of heat shock protein 72,
      acting in synergy with the bacteria.
AB  - Mycobacterium tuberculosis (Mtb) survive inside macrophages by manipulating
      microbicidal functions such as phago-lysosome fusion, production of reactive
      oxygen species and nitric oxide, and by rendering macrophages non-responsive to
      IFN-gamma. Mtb-infected lung tissue does however not only contain macrophages,
      but also significant numbers of infiltrating polymorphonuclear neutrophils (PMN).
      These are able to phagocytose and kill ingested Mtb, but are short-lived cells
      that constantly need to be removed from tissues to avoid tissue damage.
      Phagocytosis of aged or UV-induced apoptotic PMN by macrophages induce an anti
      inflammatory response in macrophages. However, in the present study, we show that
      engulfment of Mtb-induced apoptotic PMN by macrophages initiates secretion of TNF
      alpha from the macrophages, reflecting a pro-inflammatory response. Moreover, Mtb
      induced apoptotic PMN up-regulate heat shock proteins 60 and 72 (Hsp60, Hsp72)
      intracellularly and also release Hsp72 extracellularly. We found that both
      recombinant Hsp72 and released Hsp72 enhanced the pro-inflammatory response to
      both Mtb-induced apoptotic PMN and Mtb. This stimulatory effect of the
      supernatant was abrogated by depleting the Hsp72 with immunoprecipitation. These
      findings indicate that released Hsp72 from Mtb-infected PMN can trigger
      macrophage activation during the early stage of Mtb infections, thereby creating
      a link between innate and adaptive immunity.

PMID- 18328762
TI  - The alternative sigma factor sigma B of Staphylococcus aureus modulates virulence
      in experimental central venous catheter-related infections.
AB  - The impact of the alternative sigma factor sigma B (SigB) on pathogenesis of
      Staphylococcus aureus is not conclusively clarified. In this study, a central
      venous catheter (CVC) related model of multiorgan infection was used to
      investigate the role of SigB for the pathogenesis of S. aureus infections and
      biofilm formation in vivo. Analysis of two SigB-positive wild-type strains and
      their isogenic mutants revealed uniformly that the wild-type was significantly
      more virulent than the SigB-deficient mutant. The observed difference in
      virulence was apparently not linked to the capability of the strains to form
      biofilms in vivo since wild-type and mutant strains were able to produce biofilm
      layers inside of the catheter. The data strongly indicate that the alternative
      sigma factor SigB plays a role in CVC-associated infections caused by S. aureus.

PMID- 18328763
TI  - Genetic analysis of Kashmiri Muslim population living in Pakistan.
AB  - The PowerPlex 16 amplification kit was used for the analysis of 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) in
      unrelated, autochthonous healthy adults from Kashmiri refugee population in
      Pakistani Punjab (n=125). The allelic distributions were in Hardy-Weinberg
      equilibrium in all of loci examined except for the vWA locus. Forensic parameters
      were calculated and a comparison was made with geographically nearby populations.

PMID- 18328764
TI  - Improved synthesis of chalconoid-like compounds under ultrasound irradiation.
AB  - Claisen-Schmidt condensation of various substituted acetophenones with
      cinnamaldehyde catalyzed by KF-Al2O3 results chalconoid-like compounds, (2E,4E)
      1,5-diarylpenta-2,4-dien-1-ones, in 67-92% yields in 5-60 min under ultrasound
      irradiation.

PMID- 18328765
TI  - The spectrum of retinal dystrophies caused by mutations in the peripherin/RDS
      gene.
AB  - Peripherin/rds is an integral membrane glycoprotein, mainly located in the rod
      and cone outer segments. The relevance of this protein to photoreceptor outer
      segment morphology was first demonstrated in retinal degeneration slow (rds)
      mice. Thus far, over 90 human peripherin/RDS gene mutations have been identified.
      These mutations have been associated with a variety of retinal dystrophies, in
      which there is a remarkable inter- and intrafamilial variation of the retinal
      phenotype. In this paper, we discuss the characteristics of the peripherin/RDS
      gene and its protein product. An overview is presented of the broad spectrum of
      clinical phenotypes caused by human peripherin/RDS gene mutations, ranging from
      various macular dystrophies to widespread forms of retinal dystrophy such as
      retinitis pigmentosa. Finally, we review the proposed genotype-phenotype
      correlation and the pathophysiologic mechanisms underlying this group of retinal
      dystrophies.

PMID- 18328766
TI  - Accuracy of stereotactic electrode placement in deep brain stimulation by
      intraoperative computed tomography.
AB  - The purpose of this study was to evaluate the accuracy of stereotactic electrode
      placement in patients undergoing deep brain stimulation by using pre- and
      postoperative computed tomography (CT). Twenty-three patients with movement
      disorders (Parkinson's disease (n=7), tremor (n=9), dystonia (n=7)) treated with
      bilateral deep brain stimulation (DBS) (overall 46 target points) were
      investigated. The target point of the electrode was planned stereotactically in
      combination with a preoperative stereotactic helical computed tomography (CT). A
      postoperative CT, which was carried out still in the operating room while the
      patient had the stereotactic frame on the head, was performed in order to control
      the position of the electrodes in relation to the previously planned target
      point. The position of the four electrode contacts was measured according to the
      Talairach space (AC-PC line) and compared with the coordinates of the planned
      target point. The mean spatial distance of planned target perpendicular to the
      electrode was 1.32+/-0.75mm. These results show the high accuracy of stereotactic
      implantation of DBS electrodes assisted by pre- and postoperative image fusion
      with computed tomography (CT).

PMID- 18328767
TI  - Early neuropsychological detection and the characteristics of Parkinson's disease
      associated with mild dementia.
AB  - Parkinson's disease (PD) may exhibit patterns of cognitive deficits, yet
      physicians are currently lacking operational criteria to define the clinical
      boundaries between PD and PD dementia (PDD). Therefore, we investigated the
      characteristics of the cognitive impairments in mild PDD. We recruited 30 PDD, 20
      PD-MCI (PD with mild cognitive impairment without dementia) and 33 controls. All
      subjects were evaluated with detailed neuropsychological tests. Our results
      showed that visual memory, visuospatial functions, naming and calculation
      displayed more marked impairment than that of the other domains. Thus we suggest
      that adding cognitive dysfunctions of cortical type to the early cognitive
      deficits of PD-MCI can help predict the development of dementia.

PMID- 18328768
TI  - Antiparkinsonian therapy modifications in PD patients after STN DBS: a
      retrospective observational analysis.
AB  - OBJECTIVE: This study reports a retrospective analysis of 67 consecutive
      parkinsonian patients to assess changes in antiparkinsonian medications after
      Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN). METHODS: All
      antiparkinsonian drugs, including levodopa, dopamine agonists, associated drugs
      such as COMT and MAO inhibitors, amantadine and anticholinergics, were evaluated
      pre- and post-operatively at 1 and 3 years follow-up. RESULTS: The levodopa mean
      daily dose was reduced approximately 60% after 1 year and remained stable after 3
      years. Apomorphine, bromocriptine, tolcapone, entacapone and selegiline were
      withdrawn after STN DBS. Three years post-operatively, 9 patients (13.4%) no
      longer required levodopa and 6 patients (8.9%) completely stopped all
      dopaminergic medications. More patients were on monotherapy of either levodopa or
      dopamine agonist and fewer patients required a combined treatment of dopamine
      agonist and levodopa, compared to the pre-surgical condition. CONCLUSIONS: STN
      DBS treated PD patients experience a significant long-term reduction and
      simplification of the pharmacological treatment.

PMID- 18328769
TI  - Unified Parkinson's Disease Rating Scale (UPDRS) part I as a screening and
      diagnostic instrument for apathy in patients with Parkinson's disease.

PMID- 18328770
TI  - Voxel-wise analysis of diffusion tensor MRI improves the confidence of diagnosis
      of corticobasal degeneration non-invasively.
AB  - Corticobasal degeneration (CBD) presents with symptoms that often overlap with
      other neurological conditions. In many cases, diagnosis, prognosis and consequent
      clinical management remain uncertain. Structural and functional asymmetric brain
      changes represent the most consistent imaging findings that may assist in CBD
      diagnosis. Diffusion Tensor MRI (DT-MRI) is a quantitative technique that allows
      microscopic tissue abnormalities to be non-invasively assessed in vivo. A single
      case of clinically suspected CBD with symmetric diffuse brain atrophy on
      conventional-MRI scans was studied using DT-MRI by voxel-wise comparison with
      eight healthy subjects. The lateralized distribution of DT-MRI abnormalities was
      consistent with clinical features providing a substantial support to the
      diagnosis.

PMID- 18328771
TI  - Photophobia, visual hallucinations, and REM sleep behavior disorder in
      progressive supranuclear palsy and corticobasal degeneration: a prospective
      study.
AB  - Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) have
      overlapping clinical features that can make clinical distinction between these
      two entities difficult. The present study compared the frequency of photophobia,
      visual hallucinations, and REM sleep behavior disorder (RBD) in patients
      clinically diagnosed with PSP to those clinically suspected to have CBD.
      Photophobia occurred in all 10 (100%) PSP patients vs 2 (18%) patients with
      clinically suspected CBD (p=0.0002). Visual hallucinations and RBD occurred in
      patients with PSP and CBD but were rare occurrences (5% for each symptom). The
      presence of photophobia is significantly more frequent in clinically diagnosed
      PSP than CBD and can be used as a feature in differentiating between the two
      diseases in clinical practice. Visual hallucinations and RBD occur infrequently
      in PSP and CBD and are not useful symptoms in clinical differentiation.

PMID- 18328772
TI  - Associations of neighborhood problems and neighborhood social cohesion with
      mental health and health behaviors: the Multi-Ethnic Study of Atherosclerosis.
AB  - Few studies have investigated the specific features implicated in neighborhood
      health associations. We examined associations between measures of neighborhood
      problems and neighborhood social cohesion with depression, smoking, drinking, and
      walking for exercise in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
      Neighborhoods were characterized according to participant self-report and
      aggregated measures based on other MESA participants. Individuals living in the
      least problematic neighborhoods were significantly less likely to be depressed,
      to smoke, or to drink. Less socially cohesive neighborhoods were associated with
      increased depression, smoking, and not walking for exercise. Results persisted
      after adjusting for individual-level variables. Each measure appeared to capture
      distinct features of the neighborhood and associations did not differ by
      race/ethnicity. Results for neighborhood problems were robust to the use of
      aggregate measures but results for social cohesion generally were not. Future
      work should determine the health effect of modifying specific features of the
      neighborhood context.

PMID- 18328774
TI  - Do perennials really senesce?
AB  - Although senescence remains less studied in perennials than in monocarpic plants,
      major advances in understanding senescence in perennials have been achieved
      recently. This success is due not only to the use of genetic tools in woody
      plants but also to a renaissance of research on how perennials can live for
      centuries or even millennia. The particularities of perennial life are considered
      here, with an emphasis on how these affect senescence at different levels of
      organization. I conclude that although cellular and leaf senescence do share
      common features in monocarpic and perennial plants, the indeterminacy of
      meristems found in perennials begs the question of whether senescence really
      occurs in these organisms at the whole-plant level.

PMID- 18328773
TI  - Extracellular calcium as an integrator of tissue function.
AB  - The past several decades of research into calcium signaling have focused on
      intracellular calcium (Ca(i)(2+)), revealing both exquisite spatial and dynamic
      control of this potent second messenger. Our understanding of Ca(i)(2+) signaling
      has benefited from the evolution of cell culture methods, development of high
      affinity fluorescent calcium indicators (both membrane-permeant small molecules
      and genetically encoded proteins), and high-resolution fluorescence microscopy.
      As our understanding of single cell calcium dynamics has increased, translational
      efforts have attempted to push calcium signaling studies back into tissues,
      organs and whole animals. Emerging results from these more complicated, diffusion
      limited systems have begun to define a role for extracellular calcium (Ca(o)(2+))
      as an agonist, spurred by the cloning and characterization of a G protein-coupled
      receptor activated by Ca(o)(2+) (the calcium sensing receptor, CaR). Here, we
      review the current state-of-the art for measurement of Ca(o)(2+) fluctuations,
      and the evidence that fluctuations in Ca(o)(2+) can act as primary signals
      regulating cell function. Current results suggest that Ca(o)(2+) in bone and
      epidermis may act as a chemotactic homing signal, targeting cells to the
      appropriate tissue locations prior to initiation of the differentiation program.
      Ca(i)(2+) signaling-mediated Ca(o)(2+) fluctuations in interstitial spaces may
      integrate cell signaling responses in multicellular networks through activation
      of CaR. Appreciation of the importance of Ca(o)(2+) fluctuations in coordinating
      cell function will likely spur identification of additional, niche-specific
      Ca(2+) sensors, and provide unique insights into the regulation of multicellular
      signaling networks.

PMID- 18328775
TI  - How do environmental stresses accelerate photoinhibition?
AB  - Environmental stress enhances the extent of photoinhibition, a process that is
      determined by the balance between the rate of photodamage to photosystem II
      (PSII) and the rate of its repair. Recent investigations suggest that exposure to
      environmental stresses, such as salt, cold, moderate heat and oxidative stress,
      do not affect photodamage but inhibit the repair of PSII through suppression of
      the synthesis of PSII proteins. In particular, production of D1 protein is
      downregulated at the translation step by the direct inactivation of the
      translation machinery and/or by primarily interrupting the fixation of CO2. The
      latter results in the creation of reactive oxygen species (ROS), which in turn
      block the synthesis of PSII proteins in chloroplasts.

PMID- 18328776
TI  - Management of clinically negative neck for the patients with head and neck
      squamous cell carcinomas in the modern era.
AB  - Management of the cervical metastases is of paramount importance in the treatment
      of patients with head and neck squamous cell carcinoma (HNSCC). Head and neck
      oncologists continue to debate the appropriate approach of the clinically
      negative neck among patients with HNSCC. There are three management options: (A)
      Observation, reserving therapeutic neck dissection for only those patients who
      subsequently develop metastatic disease in the neck. (B) Staging with reserving
      definitive treatment for those who are found to have subclinical disease in the
      neck. Staging may require the use of imaging techniques or "staging" neck
      dissection. In the latter case a selective neck dissection (SND) is usually
      recommended, but it is still controversial if this surgical procedure for
      clinically negative neck is a staging or a therapeutic approach. (C) Elective
      treatment of the neck using neck dissection, radiation therapy or both. All these
      strategies may be appropriate, depending on the clinical circumstances and will
      be discussed in this review.

PMID- 18328777
TI  - Spectroscopic studies of transition metal complexes with a N-donor
      tetradentate(N4) 12-membered macrocylic ligand.
AB  - Chromium(III), manganese(II), iron(III), cobalt(II), nickel(II), copper(II),
      ruthenium(III), iridium(III), palladium(II) and platinum(II) complexes were
      synthesized with a 12-membered 1,4,7,10-tetraazadodeca-5,6,11,12-tetraene
      macrocylic ligand (L) and characterized by elemental analysis, molar conductance,
      magnetic susceptibility, IR, electronic, EPR and Mossbauer [Fe(III)] spectral
      studies. The molar conductance measurements of all the complexes in DMF solution
      correspond to non-electrolytic nature for M(L)Cl2 complexes [where M=Mn(II),
      Co(II), Ni(II), Cu(II)], 1:1 electrolytes for M'(L)Cl3 complexes [where
      M'=Cr(III), Fe(III), Ru(III) and Ir(III)] and 1:2 electrolytes for M''(L)Cl2
      complexes [where M''=Pd(II) and Pt(II)]. Thus, the complexes may be formulated as
      [M(L)C1(2)], [M'(L)C1(2)]C1 and [M''(L)]C1(2), respectively [where L=ligand]. All
      complexes were of the high-spin type and found to have six-coordinate octahedral
      geometry except the Pd(II) and Pt(II) complexes which were four coordinate,
      square planar and diamagnetic.

PMID- 18328781
TI  - Self-reported physical activity levels during a segmented school day in a large
      multiethnic sample of high school students.
AB  - The school day provides youth several opportunistic time periods to be active.
      How active youth are during these time periods or whether they engage in physical
      activity across multiple time periods is not well established. A cross-sectional
      sample of 12-18-year-old students (n=3471) were recruited from low socioeconomic
      status high schools within South Auckland, New Zealand. Participants reported
      their physical activity during lunchtime, morning recess, and after school, as
      well as their level of active transportation to and from school. For each
      physical activity opportunity participants were dichotomised as being either
      "more active" or "less active". Height, weight, and waist circumference
      measurements were also collected for each participant. Data were analysed using
      binary logistic regression to understand demographic associations and with kappa
      coefficient calculations to examine level of association in participation levels
      between different time periods. The percentage of students considered 'more
      active' depended on the physical activity variable of interest (after-school,
      56.3%; active transportation, 58.1%; morning recess, 26.4%; lunchtime recess,
      32.4%). Only 11.1% of participants were classified as 'more active' across all
      four physical activity opportunities. Substantial agreement (kappa=.68) was only
      observed in participation levels at lunchtime and morning recess. At-risk groups
      for lower physical activity were female students, senior students, and students
      of Asian/Other descent. During a school day multiple opportunistic time periods
      exist for youth to be active, yet a large proportion of students are not as
      active as they could be with few youth engaging in physical activity across
      various segments of the school day.

PMID- 18328782
TI  - Therapeutic cleavage of IgG: new avenues for treating inflammation.
AB  - Autoantibodies developing in humans contribute to the pathogenesis of several
      diseases, and injected therapeutic antibodies can also trigger adverse side
      effects. An efficient and rapid elimination of these antibodies are therefore
      critically needed. Antibody removal by plasmapheresis and immunoadsorption are
      commonly used methods but have their own limitations. Bacterial enzymes that can
      cleave IgG molecules or remove carbohydrate moieties to ameliorate their
      immunogenicity or effector functions in vivo offer new avenues for drug
      development. Recent discoveries highlight the possibility of cleaving or
      modifying IgG in vivo by injection of enzymes. Such an approach opens up new
      therapeutic possibilities not only for the control of pathogenic antibody
      mediated inflammatory diseases but also allograft rejection or the treatment of
      side-effects of 'biologicals' such as monoclonal antibodies.

PMID- 18328783
TI  - The hygiene hypothesis and psychiatric disorders.
AB  - The hygiene hypothesis proposes that several chronic inflammatory disorders
      (allergies, autoimmunity, inflammatory bowel disease) are increasing in
      prevalence in developed countries because a changing microbial environment has
      perturbed immunoregulatory circuits which normally terminate inflammatory
      responses. Some stress-related psychiatric disorders, particularly depression and
      anxiety, are associated with markers of ongoing inflammation, even without any
      accompanying inflammatory disorder. Moreover, pro-inflammatory cytokines can
      induce depression, which is commonly seen in patients treated with interleukin-2
      or interferon-alpha. Therefore, some psychiatric disorders in developed countries
      might be attributable to failure of immunoregulatory circuits to terminate
      ongoing inflammatory responses. This is discussed in relation to the effects of
      the immune system on a specific group of brain serotonergic neurons involved in
      the pathophysiology of mood disorders.

PMID- 18328784
TI  - Immunity to self and self-maintenance: a unified theory of brain pathologies.
AB  - Although there is a growing acceptance that immune cells could play a protective
      role under various injurious or pathological conditions of the central nervous
      system (CNS), the possibility that the immune system is constantly involved in
      day-to-day maintenance of CNS functional integrity has not been acknowledged.
      Here, we propose a unifying hypothesis, based on a recent collection of
      experimental results, suggesting that the loss of immunity to certain self
      antigens or its insufficiency when encountering increased levels of risk factors
      is an important underlying factor in the onset or escalation of neurodegenerative
      processes, age-related dementia or mental dysfunction. We further suggest a model
      that explains how immunity to self exerts its roles in the special immune
      privileged context of the CNS.

PMID- 18328785
TI  - Epstein-Barr virus: a paradigm for persistent infection - for real and in virtual
      reality.
AB  - The really interesting thing about herpesviruses is that they can establish
      lifelong persistant infections in immunocompetent hosts. At first glance, they
      would seem to have very different ways of doing this. Here we will use as a model
      our current understanding of how the human herpesvirus Epstein-Barr virus
      establishes and maintains such an infection. We apply information from a wide
      range of sources including laboratory experimentation, clinical observation,
      animal models and a new computer simulation. We propose that the detailed
      mechanisms for establishing infection are dependent on the virus and tissues
      involved, but the strategy is the same - to persist in a long-lived cell type
      where the virus is invisible to the immune system and nonpathogenic.

PMID- 18328786
TI  - T-cell fate and function: PKC-theta and beyond.
AB  - The serine/threonine-specific protein kinase C-theta (PKC-theta) is a core
      component of the immunological synapse that was shown in vitro to play a central
      role in the activation of T cells after T cell receptor (TCR) and co-stimulatory
      molecule engagement. In recent years, a series of in vivo studies have shown that
      the situation is far more complex; specifically, PKC-theta signaling is
      differentially required for Th1, Th2, Th17 and CD8+ cytotoxic T-cell responses.
      These studies highlight the combination of signals that directly regulate T-cell
      differentiation and effector responses. In this review, we highlight recent in
      vivo studies investigating PKC-theta function and discuss this in the context of
      how the integration of extrinsic signals determines T cell fate and function.

PMID- 18328787
TI  - Diagnosis, imaging and anatomical classification of uterine fibroids.
AB  - Uterine leiomyomata, commonly referred to as fibroids, are often accompanied by
      symptoms common to many other pelvic conditions. The correct identification of
      myomata and the exclusion of other diseases, especially malignancies, are
      imperative when evaluating therapy options. A confident diagnosis of myomata may
      be aided by several imaging modalities. The selection of an imaging technique
      should include an evaluation of both the benefits and the costs associated with
      the procedure. Imaging can provide information regarding precise myomata
      location, which may, in turn, dictate treatment options. Myomata may be
      classified based upon position within the uterus, and may be further described by
      phase of degeneration. With the increasing popularity of uterine-conserving
      therapy, accurate diagnosis of myomata becomes even more important.

PMID- 18328788
TI  - Management of symptomatic fibroids: conservative surgical treatment modalities
      other than abdominal or laparoscopic myomectomy.
AB  - Approximately 50% of women of reproductive age have fibroids, and at least 50% of
      these women have significant symptoms. However, until 15 years ago, the only
      surgical options available were hysterectomy and myomectomy, and as yet there are
      no proven effective long-term medical therapies. Fortunately, the past decade has
      witnessed the emergence of highly sophisticated diagnostic and therapeutic
      technologies for fibroids. Magnetic resonance imaging and high-resolution
      ultrasound are non-invasive, high-quality diagnostic procedures. The new
      treatment modalities include: laparoscopic and vaginal myomectomy; uterine artery
      embolization (UAE); magnetic-resonance-guided focused ultrasound surgery
      (MRgFUS); hysteroscopic resection where the fibroids are submucous; myolysis by
      heat, cold coagulation and laser; laparoscopic uterine artery occlusion; and
      temporary transvaginal uterine artery occlusion. It is, however, abundantly clear
      that there is no panacea that suits every woman, nor are all treatment types
      universally available to all women, even in the developed world. Laparoscopic
      surgery requires skills that are not common place, and there are limitations on
      the size and number of fibroids that can be treated by this modality. Much the
      same applies to vaginal myomectomy. UAE is now widely used in the USA and Western
      Europe, and has been recommended by the National Institute for Clincial
      Excellence (NICE) in the UK as an alternative therapy to hysterectomy. However,
      UAE is still under evaluation in terms of comparison with myomectomy. UAE has a
      range of complications including premature ovarian failure, chronic vaginal
      discharge and pelvic sepsis, and may have limited efficacy when the fibroids are
      large. Although there are a number of reports of successful pregnancy following
      UAE, the experience is limited and research is required in this area. MRgFUS was
      approved by the US Food and Drug Administration in 2004, while NICE recommended
      that the procedure should be used in an audit and research setting. Preliminary
      data following laparoscopic uterine artery occlusion suggest that outcomes are
      similar to those with UAE, but these data are derived from studies involving
      relatively small numbers. Temporary uterine artery occlusion is also promising,
      but has yet to be evaluated robustly. Thus there is no room for complacency;
      research involving the available treatment modalities is urgently needed, while
      innovations in search of newer and more effective therapies must continue. This
      chapter will review surgical treatment modalities other than hysterectomy and
      abdominal or laparoscopic myomectomy.

PMID- 18328789
TI  - Comparing heterogeneous SNOMED CT coding of clinical research concepts by
      examining normalized expressions.
AB  - OBJECTIVE: A continual problem confronting the implementation of standardized
      vocabularies such as SNOMED CT is that their expressive flexibility and power
      provide more than one way to represent a given concept. The goal of this study
      was to investigate how the CliniClue Expression Transformer tool could be used to
      help in discerning similarities and differences among three separate sets of
      clinical research concepts coded in SNOMED CT by three different paid expert
      coding companies. METHODS: Initial editing of the companies' coded datasets was
      required to enable accurate input into CliniClue Version: 2006.2.0030 Expression
      Transformer tool. The normal forms of the company codings for the 319 clinical
      research question/answer sets were compared to determine whether they were
      equivalent or otherwise related (e.g., if one was subsumed by the other). Basic
      frequencies were computed for (957) pairwise comparisons of each of 319 concepts
      each coded by the three expert coders, and the implications of the results
      discussed. RESULTS: The primary finding from this study was that, for each of the
      paired comparisons, approximately half of the time the companies' codings could
      be related, primarily via subsumption. The greatest percentage of equivalent
      concepts between any two companies was 33%. These same two companies also agreed
      most often on the core clinical concept measure from an earlier study by the
      authors. CONCLUSION: Heterogeneity among coders using the same controlled
      terminology appears inescapable despite the extensive efforts of terminological
      standards developers and implementers. In our study, the computable determination
      of equivalence of discordantly coded concepts still failed to yield acceptably
      comparable data. A clearer articulation, and perhaps a simplification, of rules
      for the consistent use for terminologies such as SNOMED CT is needed.

PMID- 18328790
TI  - Emodin upregulates urokinase plasminogen activator, plasminogen activator
      inhibitor-1 and promotes wound healing in human fibroblasts.
AB  - Urokinase plasminogen activator (uPA) system is important for several biological
      processes that call for extracellular proteolysis, fibrinolysis, cell migration,
      proliferation and angiogenesis. The current study highlights the fibrinolytic and
      wound healing potential of emodin, an anthraquinone, with relevance to the uPA
      system. Emodin increased the fibrinolytic activity of fibroblast cells in a dose
      dependent manner. Zymography linked the activity to increased uPA activity.
      Subsequent RT-PCR and western analyses demonstrated uPA gene upregulation.
      Interestingly, PAI-1, the inhibitor of uPA was also upregulated. EMSA showed the
      upregulation occurred independent of emodin's effect on nuclear factor kappa B
      (NFkappaB). The effect on uPA system is supposedly via generation of reactive
      oxygen species (ROS) since cotreatment with ascorbic acid, an anti-oxidant,
      attenuated the activity. In addition to profibrinolytic potential, emodin also
      demonstrated wound healing activity in in vitro wound models. Presence of emodin
      in the medium enhanced the rate of migration of fibroblasts into the wounded
      region. These in vitro experiments reveal that emodin is a potent profibrinolytic
      and wound healing agent.

PMID- 18328791
TI  - Genetic factors affecting the occurrence, clinical phenotype, and outcome of
      autoimmune hepatitis.
AB  - Autoimmune hepatitis is a polygenic disorder of unknown cause in which the
      genetic risk factors that affect occurrence, clinical phenotype, severity, and
      outcome still are being clarified. The susceptibility alleles in white North
      American and northern European patients reside on the DRB1 gene, and they are
      DRB1*0301 and DRB1*0401. These alleles encode a 6 amino acid sequence at
      positions 67-72 in the DRbeta polypeptide chain of the class II molecules of the
      major histocompatibility complex. This sequence is associated with
      susceptibility, and lysine at position DRbeta71 is the key determinant. Molecular
      mimicry between foreign and self-antigens may explain the loss of self-tolerance
      and the occurrence of concurrent immune diseases in anatomically distant organs.
      Disease severity is associated with the number of alleles encoding lysine at
      DRbeta71 (gene dose) and the number of polymorphisms, including those of the
      tumor necrosis factor-alpha gene, cytotoxic T lymphocyte antigen-4 gene, and
      tumor necrosis factor-receptor superfamily gene, that can modify the immune
      response. Individuals in different geographic regions may have different
      susceptibility alleles that reflect indigenous triggering antigens, and these may
      provide clues to the etiologic agent. Knowledge of the genetic predispositions
      for autoimmune hepatitis may elucidate pathogenic mechanisms, identify etiologic
      agents, characterize susceptible populations, foresee outcomes, and target new
      therapies. These lessons may be applicable to autoimmune disease in general.

PMID- 18328792
TI  - Undiagnosed myeloproliferative disease in cases of intra-abdominal thrombosis:
      the utility of the JAK2 617F mutation.
AB  - BACKGROUND & AIMS: Extrahepatic portal vein thrombosis and Budd-Chiari syndrome
      frequently result from multiple concurrent factors such as cirrhosis, intra
      abdominal sepsis, procoagulant states, and underlying myeloproliferative
      disorders (MPDs). The JAK2 V617F mutation is a point mutation in the Janus kinase
      2 (JAK2) tyrosine kinase that is variably present in MPDs. The incidence depends
      on the subclassification of the MPDs and the sensitivity of the assay used. This
      case series aimed to illustrate the diagnostic utility of JAK2 V617F mutation in
      atypical cases of MPD that otherwise may not have met traditional diagnostic
      criteria. METHODS: Granulocytic DNA was obtained and real-time polymerase chain
      reaction was performed using allele-specific primer and probe to provide a
      quantitative expression of the V617F mutation. RESULTS: The JAK2 V617F point
      mutation was found in 3 patients with extrahepatic portal vein thrombosis who had
      multiple thrombotic events but did not fulfill the traditional diagnostic
      criteria for MPDs. CONCLUSIONS: A sensitive assay for the JAK2 V617F mutation has
      the potential to diagnose atypical MPDs in multiple undiagnosed cases of intra
      abdominal thrombosis and therefore alter the management and prognosis of these
      patients.

PMID- 18328793
TI  - Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in
      treatment of malignant hilar biliary strictures.
AB  - BACKGROUND & AIMS: For the treatment of unresectable biliary tract carcinoma with
      hilar biliary stricture, antitumor therapy and biliary stenting should be
      addressed in terms of prolonged survival with a good quality of life. However,
      the endoscopic management of malignant hilar biliary strictures is difficult even
      for an expert endoscopist. We evaluated the efficacy and safety of the endoscopic
      deployment of multiple JOSTENT SelfX units in patients with hilar biliary
      strictures treated with or without chemotherapy. METHODS: Between November 2003
      and December 2006, endoscopic deployment of multiple JOSTENT SelfX units in hilar
      biliary strictures by using a partial stent-in-stent procedure was performed on
      41 consecutive patients with primary cholangiocarcinoma (n = 34) and gallbladder
      carcinoma (n = 7) at a gastroenterologic center of Okayama University Hospital.
      Thirty-three patients were treated with gemcitabine (n = 25) or S-1 (n = 8).
      RESULTS: Metallic stent deployment was successfully accomplished in all cases via
      only endoscopic procedures. During the follow-up period (mean, 210 days), mean
      patency time was 150 days, and metallic stent obstruction occurred in 15 cases
      (37%). Although a repeat intervention was required in all metallic stent
      obstructed cases, the deployment of the second metallic or plastic stent was
      completed successfully. The remaining 26 cases (63%) required no interventions.
      The median overall survival period was only 235 days. However, that of the
      patients receiving chemotherapy was 392 days. CONCLUSIONS: Endoscopic partial
      stent-in-stent deployment with multiple JOSTENT SelfX prostheses is effective and
      safe for the treatment of malignant hilar biliary stricture even in patients
      receiving chemotherapy.

PMID- 18328794
TI  - Specific gastroduodenoscopic findings in Crohn's disease: Comparison with
      findings in patients with ulcerative colitis and gastroesophageal reflux disease.
AB  - BACKGROUND: Crohn's disease patients often carry gastroduodenal lesions. However,
      few reports have addressed specific gastroduodenoscopic findings in Crohn's
      disease patients. METHODS: The gastroduodenoscopic findings of 63 Crohn's disease
      patients were examined. Those of 62 ulcerative colitis and 63 age- and gender
      matched gastroesophageal reflux disease patients were also reviewed as controls.
      Findings of bamboo-joint-like appearance, gastric antral erosions, and duodenal
      lesions were the specific findings that were highlighted. RESULTS: Of 63 Crohn's
      disease patients, 47 (75%) had at least one of the specific gastroduodenoscopic
      findings, and the prevalence of these findings was significantly higher in
      Crohn's disease patients than in ulcerative colitis and gastroesophageal reflux
      disease patients (ulcerative colitis, 24/62, 39%; gastroesophageal reflux
      disease, 15/63, 24%, P < 0.0001). In particular, bamboo-joint-like appearance was
      almost unique to Crohn's disease patients (Crohn's disease, 28/63, 44%;
      ulcerative colitis, 3/62, 5%; gastroesophageal reflux disease, 0/63, 0%, P <
      0.0001). Analysis of the relationship between the Crohn's disease patient's
      background and gastrodunodenoscopic findings revealed that both patients with
      disease affecting the ileum and those with previous gut operations were more
      likely to exhibit the specific gastroduodenoscopic findings (P = 0.030 and P =
      0.043, respectively). CONCLUSION: Specific gastroduodenoscopic findings were
      observed in Crohn's disease patients. In particular, bamboo-joint-like appearance
      could be a unique marker of Crohn's disease.

PMID- 18328795
TI  - Vascular endothelial growth factor immobilized in collagen scaffold promotes
      penetration and proliferation of endothelial cells.
AB  - A key challenge in engineering functional tissues in vitro is the limited
      transport capacity of oxygen and nutrients into the tissue. Inducing
      vascularization within engineered tissues is a key strategy to improving their
      survival in vitro and in vivo. The presence of vascular endothelial growth factor
      (VEGF) in a three-dimensional porous collagen scaffold may provide a useful
      strategy to promote vascularization of the engineered tissue in a controlled
      manner. To this end, we investigated whether immobilized VEGF could promote the
      invasion and assembly of endothelial cells (ECs) into the collagen scaffolds. We
      conjugated VEGF onto collagen scaffolds using N-(3-dimethylaminopropyl)-N'
      ethylcarbodiimide hydrochloride chemistry, and measured the concentrations of
      immobilized VEGF in collagen scaffolds by direct VEGF enzyme-linked immunosorbent
      assay. We demonstrated that immobilized VEGF (relative to soluble VEGF) promoted
      the penetration and proliferation of ECs in the collagen scaffold, based on
      results of cell density analysis in histological sections, immunohistochemistry,
      XTT proliferation assay, glucose consumption and lactate production. Furthermore,
      we observed increased viability of ECs cultured in scaffolds with immobilized
      VEGF relative to soluble VEGF. This research demonstrates that immobilization of
      VEGF is a useful strategy to promote the invasion and proliferation of ECs into a
      scaffold, which may in turn lead to a vascularized scaffold.

PMID- 18328796
TI  - Critical overview of Nitinol surfaces and their modifications for medical
      applications.
AB  - Nitinol, a group of nearly equiatomic shape memory and superelastic NiTi alloys,
      is being extensively explored for medical applications. Release of Ni in the
      human body, a potential problem with Nitinol implant devices, has stimulated a
      great deal of research on its surface modifications and coatings. In order to use
      any of the developed surfaces in implant designs, it is important to understand
      whether they really have advantages over bare Nitinol. This paper overviews the
      current situation, discusses the advantages and disadvantages of new surfaces as
      well as the limitations of the studies performed. It presents a comprehensive
      analysis of surface topography, chemistry, corrosion behavior, nickel release and
      biological responses to Nitinol surfaces modified mechanically or using such
      methods as etching in acids and alkaline solutions, electropolishing, heat and
      ion beam treatments, boiling in water and autoclaving, conventional and ion
      plasma implantations, laser melting and bioactive coating deposition. The
      analysis demonstrates that the presently developed surfaces vary in thickness
      from a few nanometers to micrometers, and that they can effectively prevent Ni
      release if the surface integrity is maintained under strain and if no Ni-enriched
      sub-layers are present. Whether it is appropriate to use various low temperature
      pre-treatment protocols (< or = 160 degrees C) developed originally for pure
      titanium for Nitinol surface modifications and coatings is also discussed. The
      importance of selection of original Nitinol surfaces with regard to the
      performance of coatings and comparative performance of controls in the studies is
      emphasized. Considering the obvious advantages of bare Nitinol surfaces for
      superelastic implants, details of their preparation are also outlined.

PMID- 18328797
TI  - The effect of feeding different sugar-sweetened beverages to growing female
      Sprague-Dawley rats on bone mass and strength.
AB  - Consumption of sugar beverages has increased among adolescents. Additionally, the
      replacement of sucrose with high fructose corn syrup (HFCS) as the predominant
      sweetener has resulted in higher fructose intake. Few studies have investigated
      the effect of drinking different sugar-sweetened beverages on bone, despite
      suggestions that sugar consumption negatively impacts mineral balance. The
      objective of this study was to determine the effect of drinking different sugar
      sweetened beverages on bone mass and strength. Adolescent (age 35d) female
      Sprague-Dawley rats were randomly assigned (n=8-9/group) to consume deionized
      distilled water (ddH2O, control) or ddH2O containing 13% w/v glucose, sucrose,
      fructose or high fructose corn syrup (HFCS-55) for 8weeks. Tibia and femur
      measurements included bone morphometry, bone turnover markers, determination of
      bone mineral density (BMD) and bone mineral content (BMC) by dual energy X-ray
      absorptiometry (DXA) and bone strength by three-point bending test. The effect of
      sugar-sweetened beverage consumption on mineral balance, urinary and fecal
      calcium (Ca) and phosphorus (P) was measured by inductively coupled plasma
      optical emission spectrometry. The results showed no difference in the bone mass
      or strength of rats drinking the glucose-sweetened beverage despite their having
      the lowest food intake, but the highest beverage and caloric consumption. Only in
      comparisons among the rats provided sugar-sweetened beverage were femur and tibia
      BMD lower in rats drinking the glucose-sweetened beverage. Differences in bone
      and mineral measurements appeared most pronounced between rats drinking glucose
      versus fructose-sweetened beverages. Rats provided the glucose-sweetened beverage
      had reduced femur and tibia total P, reduced P and Ca intake and increased
      urinary Ca excretion compared to the rats provided the fructose-sweetened
      beverage. The results suggested that glucose rather than fructose exerted more
      deleterious effects on mineral balance and bone.

PMID- 18328798
TI  - Cooperativity of cytochrome P450 1A2: interactions of 1,4-phenylene diisocyanide
      and 1-isopropoxy-4-nitrobenzene.
AB  - Homotropic cooperativity of 1-alkoxy-4-nitrobenzene substrates and also their
      heterotropic cooperative binding interactions with the iron ligand 1,4-phenylene
      diisocyanide (Ph(NC)2) had been demonstrated previously with rabbit cytochrome
      P450 (P450) 1A2 [G.P. Miller, F.P. Guengerich, Biochemistry 40 (2001) 7262-7272].
      Multiphasic kinetics were observed for the binding of Ph(NC)2 to both ferric and
      ferrous P450 1A2, including relatively slow steps. Ph(NC)2 induced an apparently
      rapid change in the circular dichroism spectrum, consistent with a structural
      change, but had no effect on tryptophan fluorescence. Ph(NC)2 binds the P450 iron
      in both the ferric and ferrous forms; ferric P450 1A2 was reduced rapidly in the
      absence of added ligands, and the rate was attenuated when Ph(NC)2 was bound. No
      oxidation products of Ph(NC)2 were detected. Docking studies with a rabbit P450
      1A2 homology model based on the published structure of a human P450 1A2.alpha
      naphthoflavone (alphaNF) complex indicated adequate room for a complex with
      either two 1-isopropoxy-4-nitrobenzene molecules or a combination of one 1
      isopropoxy-4-nitrobenzene and one Ph(NC)2; in the case of alphaNF no space for an
      extra ligand was available. The patterns of homotropic cooperativity seen with 1
      alkoxy-4-nitrobenzenes (biphasic plots of v vs. S) differ from those seen with
      polycyclic hydrocarbons (positive cooperativity), suggesting that only with the
      latter does the ligand interaction produce improved catalysis. Consistent with
      this view, Ph(NC)2 inhibited the oxidation of 1-isopropoxy-4-nitrobenzene and
      other substrates.

PMID- 18328799
TI  - Charge transfer in P-type ATPases investigated on planar membranes.
AB  - Planar lipid bilayers, e.g., black lipid membranes (BLM) and solid supported
      membranes (SSM), have been employed to investigate charge movements during the
      reaction cycle of P-type ATPases. The BLM/SSM method allows a direct measurement
      of the electrical currents generated by the cation transporter following chemical
      activation by a substrate concentration jump. The electrical current transients
      provides information about the reaction mechanism of the enzyme. In particular,
      the BLM/SSM technique allows identification of electrogenic steps which in turn
      may be used to localize ion translocation during the reaction cycle of the pump.
      In addition, using the high time resolution of the technique, especially when
      rapid activation via caged ATP is employed, rate constants of electrogenic and
      electroneutral steps can be determined. In the present review, we will discuss
      the main results obtained by the BLM and SSM methods and how they have
      contributed to unravel the transport mechanism of P-type ATPases.

PMID- 18328800
TI  - The plasma membrane Ca2+ ATPase of animal cells: structure, function and
      regulation.
AB  - Most important processes in cell life are regulated by calcium (Ca2+). A number
      of mechanisms have thus been developed to maintain the concentration of free Ca2+
      inside cells at the level (100-200nM) necessary for the optimal operation of the
      targets of its regulatory function. The systems that move Ca2+ back and forth
      across membranes are important actors in its control. The plasma membrane calcium
      ATPase (PMCA pump) which ejects Ca2+ from all eukaryotic cell types will be the
      topic of this contribution. The pump uses a molecule of ATP to transport one
      molecule of Ca2+ from the cytosol to the external environment. It is a P-type
      ATPase encoded by four genes (ATP2B1-4), the transcripts of which undergo
      different types of alternative splicing. Many pump variants thus exist. Their
      multiplicity is best explained by the specific Ca2+ demands in different cell
      types. In keeping with these demands, the isoforms are differently expressed in
      tissues and cell types and have differential Ca2+ extruding properties. At very
      low Ca2+ concentrations the PMCAs are nearly inactive. They must be activated by
      calmodulin, by acid phospholipids, by protein kinases, and by other means, e.g.,
      a dimerization process. Other proteins interact with the PMCAs (i.e., MAGUK and
      NHERF at the PDZ domain and calcineurin A in the main intracellular domain) to
      sort them to specific regions of the cell membrane or to regulate their function.
      In some cases the interaction is isoform, or even splice variant specific. PMCAs
      knock out (KO) mice have been generated and have contributed information on the
      importance of PMCAs to cells and organisms. So far, only one human genetic
      disease, hearing loss, has been traced back to a PMCA defect.

PMID- 18328801
TI  - Insulin action and signalling in fat and muscle from dexamethasone-treated rats.
AB  - Glucocorticoids initiate whole body insulin resistance and the aim of the present
      study was to investigate effects of dexamethasone on protein expression and
      insulin signalling in muscle and fat tissue. Rats were injected with
      dexamethasone (1mg/kg/day, i.p.) or placebo for 11 days before insulin
      sensitivity was evaluated in vitro in soleus and epitrochlearis muscles and in
      isolated epididymal adipocytes. Dexamethasone treatment reduced insulin
      stimulated glucose uptake and glycogen synthesis by 30-70% in epitrochlearis and
      soleus, and insulin-stimulated glucose uptake by approximately 40% in adipocytes.
      8-bromo-cAMP-stimulated lipolysis was approximately 2-fold higher in adipocytes
      from dexamethasone-treated rats and insulin was less effective to inhibit cAMP
      stimulated lipolysis. A main finding was that dexamethasone decreased expression
      of PKB and insulin-stimulated Ser(473) and Thr(308) phosphorylation in both
      muscles and adipocytes. Expression of GSK-3 was not influenced by dexamethasone
      treatment in muscles or adipocytes and insulin-stimulated GSK-3beta Ser(9)
      phosphorylation was reduced in muscles only. A novel finding was that glycogen
      synthase (GS) Ser(7) phosphorylation was higher in both muscles from
      dexamethasone-treated rats. GS expression decreased (by 50%) in adipocytes only.
      Basal and insulin-stimulated GS Ser(641) and GS Ser(645,649,653,657)
      phosphorylation was elevated in epitrochlearis and soleus muscles and GS
      fractional activity was reduced correspondingly. In conclusion, dexamethasone
      treatment (1) decreases PKB expression and insulin-stimulated phosphorylation in
      both muscles and adipocytes, and (2) increases GS phosphorylation (reduces GS
      fractional activity) in muscles and decreases GS expression in adipocytes. We
      suggest PKB and GS as major targets for dexamethasone-induced insulin resistance.

PMID- 18328802
TI  - Localization of the Sodium-Taurocholate cotransporting polypeptide in membrane
      rafts and modulation of its activity by cholesterol in vitro.
AB  - BACKGROUND: The relevance of discrete localization of hepatobiliary transporters
      in specific membrane microdomains is not well known. AIM: To determine whether
      the Na+/taurocholate cotransporting polypeptide (Ntcp), the main hepatic
      sinusoidal bile salt transporter, is localized in specific membrane microdomains.
      METHODS: Presence of Ntcp in membrane rafts obtained from mouse liver was studied
      by immunoblotting and immunofluorescence. HEK-293 cells stably transfected with
      rat Ntcp were used for in vitro studies. Expression, localization and function of
      Ntcp in these cells were assessed by immunoblotting, immunofluorescence and
      biotinylation studies and Na+ -dependent taurocholate uptake assays,
      respectively. The effect of cholesterol depletion/repletion assays on Ntcp
      function was also investigated. RESULTS: Ntcp localized primarily to membrane
      rafts in in vivo studies and localized partially in membrane rafts in transfected
      HEK-293 cells. In these cells, membrane cholesterol depletion resulted in a shift
      of Ntcp localization into non-membrane rafts, which correlated with a 2.5-fold
      increase in taurocholate transport. Cholesterol repletion shifted back part of
      Ntcp into membrane rafts, and normalized taurocholate transport to values similar
      to control cells. CONCLUSION: Ntcp localizes in membrane rafts and its
      localization and function are regulated by membrane cholesterol content. This may
      serve as a novel regulatory mechanism of bile salt transport in liver.

PMID- 18328803
TI  - Role of AMP-activated protein kinase in autophagy and proteasome function.
AB  - In this work, we have examined the possible role of AMP-activated protein kinase
      (a key energy sensor) in regulating intracellular protein degradation. We have
      found that AICAR, a known activator of AMPK, has a dual effect. On one hand, it
      inhibits autophagy by a mechanism independent of AMPK activity; AICAR decreases
      class III PI3-kinase binding to beclin-1 and this effect counteracts and reverses
      the known positive effect of AMPK activity on autophagy. On the other hand, AICAR
      inhibits the proteasomal degradation of proteins by an AMPK-dependent mechanism.
      This is a novel function of AMPK that allows the regulation of proteasomal
      activity under conditions of energy demand.

PMID- 18328804
TI  - Isofagomine increases lysosomal delivery of exogenous glucocerebrosidase.
AB  - Intravenous enzyme replacement therapy (ERT) with purified glucocerebrosidase
      (GLA) leads to significant improvement of the clinical manifestations in patients
      with Type 1 Gaucher disease. However, the high doses required, slow response and
      inability to recover most of the infused enzyme in the target tissues may be
      attributed to losses occurring during transit en route to the lysosome.
      Preincubation of GLA with isofagomine (IFG), a slow-binding inhibitor,
      significantly increased stability of the enzyme to heat, neutral pH and
      denaturing agents in vitro. Preincubation of GLA with isofagomine prior to uptake
      by cultured cells results in increased intracellular enzyme activity accompanied
      by an increase in enzyme protein suggesting that reduced denaturation of GLA in
      the presence of isofagomine leads to a decrease in the degradation of the enzyme
      after internalization. Preincubation of GLA with slow-binding inhibitors before
      infusion may improve the effectiveness of ERT for Gaucher disease.

PMID- 18328805
TI  - alpha-Tocopherol disturbs macrophage LXRalpha regulation of ABCA1/G1 and
      cholesterol handling.
AB  - Based on the oxidation hypothesis high doses of alpha-tocopherol have been
      advocated to prevent atherosclerosis, but clinical trials failed to demonstrate a
      benefit. As specific oxylipids activate PPARgamma and LXRalpha, master regulators
      of lipid metabolism and cholesterol exporters, we hypothesized, that high dose
      alpha-tocopherol might interfere with reverse cholesterol transport out of the
      vessel wall. Human THP-1 cells, a foam cell model, were preincubated with alpha
      tocopherol or carrier before exposure to oxidized LDL, delipidated HDL or control
      buffer. Specific mRNAs were quantified by real-time RT-PCR, LXRalpha activation
      by a reporter gene assay and cellular cholesterol homeostasis by oxLDL and dHDL
      facilitated uptake and efflux assays. alpha-Tocopherol significantly reduced
      baseline expression and stimulation by oxLDL of LXRalpha activity, CD36, ABCA1,
      and ABCG1. alpha-Tocopherol also reversed the suppression of CD36 and ABCA1 by
      dHDL. Thus alpha-Tocopherol compromises cellular lipid scavenging and channelling
      of cholesterol into reverse transport out of the vessel wall.

PMID- 18328806
TI  - DeltaNp63/BMP-7-dependent expression of matrilin-2 is involved in keratinocyte
      migration in response to wounding.
AB  - p63 is expressed as multiple variants including TA and DeltaN forms. Since p63
      deficient mice displayed profound defects of stratified epithelia, p63 is an
      essential transcription factor required for epidermal morphogenesis. However,
      precise molecular mechanisms behind contribution of p63 to normal skin formation
      and healing skin wounds remained unclear. In this study, we demonstrated that
      DeltaNp63/BMP-7 signaling pathway modulates wound healing process through the
      regulation of extracellular matrix protein matrilin-2. Knocking down of DeltaNp63
      in human keratinocyte HaCaT cells led to a significant reduction of matrilin-2.
      Intriguingly, BMP-7 which is one of DeltaNp63-target gene products, induced
      matrilin-2 and attenuated inhibitory effect of siRNA against DeltaNp63 on
      matrilin-2. Furthermore, a remarkable cell migration in response to wounding took
      place in DeltaNp63- or matrilin-2-knocked down cells. Taken together, our present
      findings indicate that DeltaNp63/BMP-7 signaling pathway modulates wound healing
      process through the regulation of matrilin-2.

PMID- 18328807
TI  - Caveolin-1 sensitizes vascular smooth muscle cells to mildly oxidized LDL-induced
      apoptosis.
AB  - Oxidized low-density lipoprotein (oxLDL)-induced apoptosis of vascular cells may
      participate to plaque instability and rupture. Caveolin-1 has emerged as an
      important regulator of several signal transduction pathways and processes that
      play a role in atherosclerosis. In this study we examined the potential role of
      caveolin-1 in the regulation of oxLDL-induced Ca(2+) signaling and apoptosis in
      vascular smooth muscle cells (VSMC). Cells expressing caveolin-1 were more
      susceptible to oxLDL-induced apoptosis, and this was correlated with enhanced
      Ca(2+) entry and pro-apoptotic events. Moreover, caveolin-1 silencing by small
      interfering RNA decreased the level of apoptotic cells after oxLDL treatment.
      These findings provide new insights about the potential role of caveolin-1 in the
      regulation of oxLDL-induced apoptosis in vascular cells and its contribution to
      the instability of the plaque.

PMID- 18328808
TI  - Chondrocyte acting as phagocyte to internalize polyethylene wear particles and
      leads to the elevations of osteoarthritis associated NO and PGE2.
AB  - It remains a mystery about the role of chondrocyte or cartilage on the co
      existence of ultra-high molecular weight polyethylene (UHMWPE) wear particles
      from partial joint arthroplasty. An inverted co-culture system was performed to
      investigate the interactions between chondrocytes and UHMWPE wear particles. It
      was first time observed that chondrocytes can engulf UHMWPE particles and release
      osteoarthritis associated pro-inflammatory factors. TEM observation and flow
      cytometric analysis demonstrated the phagocytosis of particles by chondrocytes.
      It was found that polyethylene particles may reduce the viability of
      chondrocytes, and enhance the secretion of nitric oxide (NO) and PGE(2). In
      conclusion, all these phenomena may contribute to further cartilage degeneration
      after partial joint arthroplasty surgery. It is first identified in this study
      that the chondrocyte acts as phagocyte to internalize wear particles and leads to
      the elevations of precursor mediators of osteoarthritis.

PMID- 18328809
TI  - A functional polymorphism of the TNF-alpha gene that is associated with type 2
      DM.
AB  - To examine the association of the tumor necrosis factor-alpha (TNF-alpha) gene
      region with type 2 diabetes (DM), 11 single-nucleotide polymorphisms (SNPs) of
      the region were analyzed. The initial study using a sample set (148 cases vs. 227
      controls) showed a significant association of the SNP IVS1G+123A of the TNF-alpha
      gene with DM (p=0.0056). Multiple logistic regression analysis using an enlarged
      sample set (225 vs. 716) revealed the significant association of the SNP with DM
      independently of any clinical traits examined (OR: 1.49, p=0.014). The functional
      relevance of the SNP were examined by the electrophoretic mobility shift assays
      using nuclear extracts from the U937 and NIH3T3 cells and luciferase assays in
      these cells with Simian virus 40 promoter- and TNF-alpha promoter-reporter gene
      constructs. The functional analyses showed that YY1 transcription factor bound
      allele-specifically to the SNP region and, the IVS1+123A allele had an increase
      in luciferase expression compared with the G allele.

PMID- 18328810
TI  - Stationary phase induced alterations in mycobacterial RNA polymerase assembly: A
      cue to its phenotypic resistance towards rifampicin.
AB  - Rapid emergence of multi-drug resistance in Mycobacterium tuberculosis has
      necessitated the development of newer candidate drugs which can selectively
      inhibit the growth of the organism. Among the best targets available today,
      transcription machinery is, by far, the most important one and the antibiotic
      rifampicin binds to a specific site on the enzyme RNA polymerase. However, it is
      not very effective towards the stationary phase of the organism or the
      persistors. In order to address this problem, we report here a protocol for
      generating an affinity tagged RNA polymerase, which can be purified easily from
      different phases of growth of the organism. It allows exploring RNAP associated
      proteins, which may confer resistance to rifampicin, using the approach of
      functional proteomics.

PMID- 18328811
TI  - Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific
      protein 1 (Sp1) binding sites.
AB  - Carboxylesterase 1 (CES1) is involved in metabolic activation of a variety of
      prodrugs into active derivatives and plays an important role in pharmacokinetics.
      We previously reported that a single nucleotide polymorphism (SNP), -816A/C of
      the CES1A2 gene associates with the responsiveness to an angiotensin-converting
      enzyme (ACE) inhibitor, imidapril, whose activity is achieved by CES1. To
      identify relevant functional polymorphisms, we re-sequenced the CES1A2 promoter
      region ( approximately 1kb) in 100 Japanese hypertensive patients. Altogether 10
      SNPs and one insertion/deletion (I/D) were identified, among which seven SNPs and
      one I/D residing between -62 and -32 were in almost complete linkage
      disequilibrium (D'=1.00, r2=0.97). They consisted a minor and a major haplotype,
      the allele frequencies of which were 22% and 74%, respectively. The minor
      haplotype possessed two putative Sp1 binding sites while the major haplotype did
      not have any Sp1 binding site. The minor haplotype had a higher transcription and
      Sp1 binding activities than the major haplotype, invitro. The original -816A/C
      was in high linkage disequilibrium with these haplotypes (D'=0.92, r2=0.85), and
      well agreed with the efficacy of imidapril medication. These results suggest that
      the Sp1 binding site variation in the CES1A2 promoter is functional, and are good
      candidates for the pharmacogenetic studies of CES1-activated drugs.

PMID- 18328812
TI  - Bis(7)-tacrine prevents glutamate-induced excitotoxicity more potently than
      memantine by selectively inhibiting NMDA receptors.
AB  - We have recently reported that bis(7)-tacrine could prevent glutamate-induced
      neuronal apoptosis through NMDA receptors. In this study, we demonstrated that in
      cultured rat cortical neurons, bis(7)-tacrine (IC(50), 0.02 microM) prevented
      glutamate-induced excitotoxicity more substantially than memantine (IC(50), 0.7
      microM). In addition, bis(7)-tacrine was more efficient than memantine in
      buffering the intracellular Ca(2+) triggered by glutamate. In cultured rat
      hippocampal neurons, bis(7)-tacrine inhibited 50 microM NMDA-activated current in
      a concentration-dependent manner with an IC(50) of 0.68+/-0.07 microM, which is
      five times more potent than that produced by memantine (IC(50), 3.41+/-0.36
      microM; p<0.05). By contrast, bis(7)-tacrine, up to 5 microM, did not
      significantly affect the current activated by 50 microM AMPA or 50 microM
      kainate. These results suggest that bis(7)-tacrine is more potent than memantine
      against glutamate-induced neurotoxicity by selectively inhibiting NMDA-activated
      current.

PMID- 18328813
TI  - The R215W mutation in NBS1 impairs gamma-H2AX binding and affects DNA repair:
      molecular bases for the severe phenotype of 657del5/R215W Nijmegen breakage
      syndrome patients.
AB  - Nijmegen breakage syndrome (NBS) is a genetic disorder characterized by
      chromosomal instability and hypersensitivity to ionising radiation. Compound
      heterozygous 657del5/R215W NBS patients display a clinical phenotype more severe
      than the majority of NBS patients homozygous for the 657del5 mutation. The NBS1
      protein, mutated in NBS patients, contains a FHA/BRCT domain necessary for the
      DNA-double strand break (DSB) damage response. Recently, a second BRCT domain has
      been identified, however, its role is still unknown. Here, we demonstrate that
      the R215W mutation in NBS1 impairs histone gamma-H2AX binding after induction of
      DNA damage, leading to a delay in DNA-DSB rejoining. Molecular modelling reveals
      that the 215 residue of NBS1 is located between the two BRCT domains, affecting
      their relative orientation that appears critical for gamma-H2AX binding. Present
      data represent the first evidence for the role of NBS1 tandem BRCT domains in
      gamma-H2AX recognition, and could explain the severe phenotype observed in
      657del5/R215W NBS patients.

PMID- 18328814
TI  - Substitution of DNA-contacting amino acids with functional variants in the Gata-1
      zinc finger: a structurally and phylogenetically guided mutagenesis.
AB  - DNA-binding functionality among transcription factor proteins is afforded by a
      number of structural motifs, such as the helix-turn-helix, helix-loop-helix, and
      zinc finger domains. The common thread among these diverse structures is their
      sequence-specific binding to essential promoter or other genetic regulatory
      sequences with high selectivity and affinity. One such motif, present in a wide
      range of organisms from bacteria to vertebrates, is the Gata-type zinc finger.
      This family of DNA-binding proteins is characterized by the presence of one or
      two (Cys)(4) metal binding sites which recognize the protein's eponymous binding
      site, GATA. Unlike other conserved DNA-binding domains, Gata proteins appear to
      be restricted to binding consensus GATA sequences, or near variations, in DNA.
      Since the architecture of the Gata finger seems built around recognizing this
      particular sequence, we set out to define the allowable range of amino acid
      substitutions along the DNA-binding surface of a Gata finger that could continue
      to support sequence-specific DNA-binding activity. Accordingly, we set up a one
      hybrid screen in yeast based on the chicken Gata-1 C-terminal zinc finger. Mutant
      libraries were generated at five amino acids identified in the Gata-DNA structure
      as likely to mediate sequence-specific contacts between the Gata finger and DNA.
      These libraries were designed to give as exhaustive amino acid coverage as
      possible such that almost all alternative amino acids were screened at each of
      the five probed positions. Screening and characterization of these libraries
      revealed several functional amino acid substitutions at two leucines which
      contact the DNA at the 3' and 5' flanks of the GATA binding site, but no
      functional substituents for amino acids near the core of the binding site. This
      pattern is consistent with amino acid sequences of known DNA-binding Gata
      fingers.

PMID- 18328815
TI  - The influence of the adiponectin gene on adiponectin concentrations and
      parameters of metabolic syndrome in non-diabetic Korean women.
AB  - BACKGROUND: Concentrations of adiponectin, the protein product of the adipocyte
      C1q and collagen-domain-containing (ADIPOQ) gene are associated with type 2
      diabetes and coronary artery disease. We investigate the association of single
      nucleotide polymorphisms (SNPs) in the ADIPOQ gene with adiponectin
      concentrations, and to parameters of metabolic syndrome. METHODS: 867 unrelated,
      non-diabetic Korean women, 20 to 69 y, were genotyped for 8 SNPs in the ADIPOQ
      gene (-11391G>A, -11377C>G, H241P, Y111H, G90S, R221S, 45T>G, 276G>T).
      Adiponectin, a homeostasis model assessment of insulin resistance (HOMA-IR), and
      metabolic parameters were measured. RESULTS: Carriers of genotype T/T at position
      276 had significantly higher adiponectin concentrations than G/G carriers
      (P=0.005). Homozygous carriers of the TG haplotype (i.e., individuals who were
      T/T at 45 and G/G at 276) and heterozygous carriers of the TG haplotype (TG/X)
      had lower adiponectin concentrations than non-TG carriers (P<0.001). Significant
      associations between SNP at 276 and serum concentrations of triglyceride
      (P=0.013), insulin (P=0.013) and HOMA-IR (P=0.012) were found. The 45-276
      haplotypes had associations identical to the 276G>T SNP. In subgroup analysis,
      subjects carrying the TG haplotype had significantly lower adiponectin
      concentrations than non-TG carriers in both normal weight (P<0.001) and
      overweight-obese (P=0.009) subgroups. The association of the TG haplotype with
      increasing insulin concentrations was significant among overweight-obese subjects
      (P=0.004), but was not significant among normal weight subjects. A similar
      association was found between the 45-276 haplotype and HOMA-IR. CONCLUSION: There
      is a strong association of the adiponectin SNP276 genotypes and the adiponectin
      45-276 haplotypes with circulating adiponectin concentrations in non-diabetic
      Korean women. In addition, this haplotype is associated with increased insulin
      concentrations and insulin resistance index only in overweight-obese individuals.

PMID- 18328816
TI  - Binding parameters and thermodynamics of the interaction of imino sugars with a
      recombinant human acid alpha-glucosidase (alglucosidase alfa): insight into the
      complex formation mechanism.
AB  - BACKGROUND: Recently, enzyme enhancement therapy (EET) for Pompe disease
      involving imino sugars, which act as potential inhibitors of acid alpha
      glucosidases in vitro, to improve the stability and/or transportation of mutant
      acid alpha-glucosidases in cells was studied and attracted interest. However, the
      mechanism underlying the molecular interaction between the imino sugars and the
      enzyme has not been clarified yet. METHODS: We examined the inhibitory and
      binding effects of four imino sugars on a recombinant human acid alpha
      glucosidase, alglucosidase alfa, by means of inhibition assaying and isothermal
      titration calorimetry (ITC). Furthermore, we built structural models of complexes
      of the catalytic domain of the enzyme with the imino sugars bound to its active
      site by homology modeling, and examined the molecular interaction between them.
      RESULTS: All of the imino sugars examined exhibited a competitive inhibitory
      action against the enzyme, 1-deoxynojirimycin (DNJ) exhibiting the strongest
      action among them. ITC revealed that one compound molecule binds to one enzyme
      molecule and that DNJ most strongly binds to the enzyme among them. Structural
      analysis revealed that the active site of the enzyme is almost completely
      occupied by DNJ. CONCLUSION: These biochemical and structural analyses increased
      our understanding of the molecular interaction between a human acid alpha
      glucosidase and imino sugars.

PMID- 18328817
TI  - Steroid 5-alpha reductase type 2 activity in biopsies from malignant and normal
      prostatic tissues.
AB  - BACKGROUND: The conversion of testosterone (T) to the more potent metabolite
      dihydrotestosterone (DHT) by prostate-specific steroid 5 alpha-reductase
      isoenzymes is a key mechanism in the action of androgens in the prostate and it
      is important in the promotion and progression of prostate diseases. We described
      an adaptation of a sensitive method for evaluation of the 5 alpha-reductase type
      2 (5 alpha-R2) activity using a small quantity of protein. METHODS: We used 29
      human prostate transrectal ultrasound-guided core biopsies obtained from patients
      (median age 70, range 55-86 y) undergoing this procedure for diagnostic purposes.
      4-[(14)C]testosterone and NADPH were incubated with biopsy homogenate. Reaction
      products were extracted, separated by thin layer chromatography and revealed by
      autoradiography. Areas correspondent to T and DHT were scraped into vials and
      their radioactivity determined. RESULTS: The 5 alpha-R2 activity was expressed as
      ln (natural logarithm). The assay was validated according to the protein
      concentration and incubation time linearities. The 5 alpha-R2 activity showed a
      significant difference between normal and neoplastic tissues with significance
      level set at P<0.05, mainly in the left prostate lobe. This was independent from
      the PSA levels. CONCLUSIONS: Determination of 5 alpha-R2 activity, using the
      conditions reported herein, could be utilized as an efficient biochemical
      parameter of prostate neoplastic processes.

PMID- 18328818
TI  - Plasma free fatty acid level patterns according to cardiovascular risk status in
      postmenopausal women.
AB  - BACKGROUND: The present study examines changes in the pattern of plasma free
      polyunsaturated fatty acids (PUFA) according to menopausal status and the
      existence of diabetes mellitus (DM) or coronary heart disease (CHD) in Korean
      women. METHODS: The participants were as follows; premenopausal women (PRE, n=20)
      and postmenopausal women without any known chronic disease (POST, n=35), with DM
      (DM, n=35), or with angiographically proven CHD (CHD, n=30). Plasma free fatty
      acids were measured in all participants. RESULTS: Healthy premenopausal women had
      a higher ratio of omega-3/omega-6 PUFA than postmenopausal women (p=0.001). As
      expected, the PRE group had higher docsapentaenoic acid (DPA) and docosahexaenoic
      acid (DHA) levels (p<0.05) and lower arachidonic acid levels (p<0.05) than the
      POST group. In turn, the healthy POST group had higher levels of DPA and DHA
      compared to the DM or CHD groups (p<0.05). There were significant shifts of
      increased omega-6 and decreased omega-3 among the women, according to each
      disease. CONCLUSIONS: There was a significant relationship between omega-3 and
      omega-6 PUFA profiles and risk for CHD in women. This metabolic profile of PUFA
      might be an important surrogate marker in postmenopausal women.

PMID- 18328819
TI  - Retinol-binding protein 4 responses during an oral glucose tolerance testing in
      women with gestational diabetes mellitus.

PMID- 18328820
TI  - Linking entries in protein interaction database to structured text: the FEBS
      Letters experiment.
AB  - The corpus of the scientific literature has reached such size that a lot of
      useful data, dispersed throughout millions different articles, are now hard to
      recover. For instance, many articles in the biological domain describe
      relationships between entities (gene, proteins, small molecules, etc.) yet this
      crucial information cannot be efficiently used because of the difficulties in
      retrieving it automatically from unstructured text. Databases are striving to
      capture this valuable information and to organize it in a structured format ready
      for automatic analysis. However, the current database model, based on manual
      curation, is not sustainable because the limited support is not compatible with
      complete and accurate coverage of published information. Several proposals have
      been put forward to increase the efficiency and accuracy of the curation process.
      Here we present an experiment, designed by the editorial board of FEBS Letters,
      aimed at integrating each manuscript with a structured summary precisely
      reporting, with database identifiers and predefined controlled vocabularies, the
      protein interactions reported in the manuscript. The authors play an important
      role in this process as they are requested to provide structured information to
      be appended, in the form of human-readable paragraphs, at the end of traditional
      summaries. It is envisaged that the structured text will become an integral part
      of Medline abstracts. In 6 months time the experience gained with this experiment
      will form the basis for a community discussion to propose a widely accepted
      strategy for information storage and retrieval.

PMID- 18328821
TI  - Finally: The digital, democratic age of scientific abstracts.

PMID- 18328822
TI  - Targeting and tinkering with interaction networks.

PMID- 18328823
TI  - Manually structured digital abstracts: a scaffold for automatic text mining.

PMID- 18328824
TI  - A text-mining perspective on the requirements for electronically annotated
      abstracts.
AB  - We propose that the combination of human expertise and automatic text-mining
      systems can be used to create a first generation of electronically annotated
      information (EAI) that can be added to journal abstracts and that is directly
      related to the information in the corresponding text. The first experiments have
      concentrated on the annotation of gene/protein names and those of organisms, as
      these are the best resolved problems. A second generation of systems could then
      attempt to address the problems of annotating protein interactions and
      protein/gene functions, a more difficult task for text-mining systems. EAI will
      permit easier categorization of this information, it will help in the evaluation
      of papers for their curation in databases, and it will be invaluable for
      maintaining the links between the information in databases and the facts
      described in text. Additionally, it will contribute to the efforts towards
      completing database information and creating collections of annotated text that
      can be used to train new generations of text-mining systems. The recent
      introduction of the first meta-server for the annotation of biological text, with
      the possibility of collecting annotations from available text-mining systems,
      adds credibility to the technical feasibility of this proposal.

PMID- 18328825
TI  - Nuclear pore complex assembly through the cell cycle: regulation and membrane
      organization.
AB  - In eukaryotes, all macromolecules traffic between the nucleus and the cytoplasm
      through nuclear pore complexes (NPCs), which are among the largest supramolecular
      assemblies in cells. Although their composition in yeast and metazoa is well
      characterized, understanding how NPCs are assembled and form the pore through the
      double membrane of the nuclear envelope and how both processes are controlled
      still remains a challenge. Here, we summarize what is known about the biogenesis
      of NPCs throughout the cell cycle with special focus on the membrane
      reorganization and the regulation that go along with NPC assembly.

PMID- 18328826
TI  - GSK-3beta-dependent destabilization of cyclin D1 mediates replicational stress
      induced arrest of cell cycle.
AB  - Chemotherapeutic agents are well known to induce growth arrest of cancerous cells
      by inducing DNA damage/replicational stress and engaging cellular apoptotic
      machinery. Our studies on hydroxyurea (HU) recognized cyclin D1 destabilization
      as the initiator of growth arrest at G(1)/S-phase independent of other cell cycle
      regulators. Cyclin D1 degradation was associated with its phosphorylation at
      Thr286 by glycogen synthase kinase-3beta and inactivation of Akt kinase.
      Overexpression of the cyclin D1(T286A) mutant, or constitutively active Akt,
      conferred stability to cyclin D1 and helped bypass cell cycle arrest. Thus,
      growth arrest by HU seems to involve destabilization of cyclin D1 in addition to
      its well-established role as ribonucleotide reductase inhibitor.

PMID- 18328827
TI  - Programmed cell death in fission yeast Schizosaccharomyces pombe.
AB  - Yeasts have proven to be invaluable, genetically tractable systems to study
      various fundamental biological processes including programmed cell death. Recent
      advances in the elucidation of the molecular pathways underlying apoptotic cell
      death in yeasts have revealed remarkable similarities to mammalian apoptosis at
      cellular, organelle and macromolecular levels, thus making a strong case for the
      relevance of yeast models of regulated cell death. Programmed cell death has been
      reported in fission yeast Schizosaccharomyces pombe, primarily in the contexts of
      perturbed intracellular lipid metabolism, defective DNA replication, improper
      mitotic entry, chronological and replicative aging. Here we review the current
      understanding of the programmed cell death in fission yeast, paying particular
      attention to lipid-induced cell death. We discuss our recent findings that
      fission yeast exhibits plasticity of apoptotic and non-apoptotic modes of cell
      death in response to different lipid stimuli and growth conditions, and that
      mitochondria, reactive oxygen species and novel cell death mediators including
      metacaspase Pca1, SpRad9 and Pck1 are involved in the lipotoxic cell death. We
      also present perspectives on how various aspects of the cell and molecular
      biology of this organism can be explored to shed light on the governing
      principles underlying lipid-mediated signaling and cell demise.

PMID- 18328828
TI  - Stabilization of scleral collagen by glycerol aldehyde cross-linking.
AB  - The paper aims at the evaluation of prospects for using glyceraldehyde as a cross
      linking agent for the scleral tissue. Stability parameters (denaturation
      temperature, Young's modulus, ultimate tensile stress, proteolytic resistance)
      and analytical parameter (fluorescence intensity) were determined during the
      glycation process of isolated rabbit sclera. The analysis of fluorescence
      spectral characteristic provided information about some glycation products. The
      glyceraldehyde treatment was resulted in a significant increase in thermal
      stability, proteolytic resistance and improvement of biomechanical
      characteristics (Young's modulus, ultimate tensile stress). Unique properties of
      the reaction between scleral collagen and glyceraldehyde are observed at short
      cross-linking times. The appearance of intermediate collagen fraction with lowest
      thermal and proteolytic stability was detected.

PMID- 18328830
TI  - Structure-directed combinatorial library design.
AB  - In recent years pharmaceutical companies have utilized structure-based drug
      design and combinatorial library design techniques to speed up their drug
      discovery efforts. Both approaches are routinely used in the lead discovery and
      lead optimization stages of the drug discovery process. Fragment-based drug
      design, a new power tool in the drug design toolbox, is also gaining acceptance
      across the pharmaceutical industry. This review will focus on the interplay
      between these three design techniques and recent developments in computational
      methodologies that enhance their integration. Examples of successful synergistic
      applications of these three techniques will be highlighted. Opinion regarding
      possible future directions of the field will be given.

PMID- 18328831
TI  - On the importance of plasmalogen status in stimulated arachidonic acid release in
      the macrophage cell line RAW 264.7.
AB  - We examined the dependence of stimulated arachidonic acid release on plasmalogens
      using the murine, macrophage cell line 264.7 and two plasmalogen-deficient
      variants, RAW.12 and RAW.108. All three strains responded to unopsinized zymosan
      to release arachidonic acid from phospholipid stores. Arachidonic acid release
      appeared to be dependent on calcium-independent phospholipase A(2) activation
      (iPLA(2)); bromoenol lactone, a specific inhibitor of calcium-independent
      iPLA(2), blocked arachidonic acid release with an IC(50) of approximately 2 x 10(
      7)M. Propanolol, an inhibitor of phosphatidate phosphatase, and RHC-80267, an
      inhibitor of diglyceride lipase, had no effect on arachidonic acid release.
      Arachidonic acid release in the variants displayed similar magnitude, kinetics of
      response and sensitivity to the inhibitors when compared to the parent strain.
      Arachidonic acid was released from all major phospholipid head group classes with
      the exception of sphingomyelin. In wild-type cells, arachidonic acid released
      from the ethanolamine phospholipids was primarily from the plasmalogen form.
      However, in the plasmalogen-deficient cells release from the diacyl species,
      phosphatidylethanolamine, was increased to compensate. Restoration of
      plasmalogens by supplementation of the growth medium with the bypass compounds sn
      1-hexadecylglycerol and sn-1-alkenylglycerol had no effect on arachidonic acid
      release. In summary, plasmalogen status appears to have no influence on the
      zymosan A stimulated release of arachidonic acid from the RAW 264.7 cell line.

PMID- 18328829
TI  - Oncolytic virotherapy: molecular targets in tumor-selective replication and
      carrier cell-mediated delivery of oncolytic viruses.
AB  - Tremendous advances have been made in developing oncolytic viruses (OVs) in the
      last few years. By taking advantage of current knowledge in cancer biology and
      virology, specific OVs have been genetically engineered to target specific
      molecules or signal transduction pathways in cancer cells in order to achieve
      efficient and selective replication. The viral infection and amplification
      eventually induce cancer cells into cell death pathways and elicit host antitumor
      immune responses to further help eliminate cancer cells. Specifically targeted
      molecules or signaling pathways (such as RB/E2F/p16, p53, IFN, PKR, EGFR, Ras,
      Wnt, anti-apoptosis or hypoxia) in cancer cells or tumor microenvironment have
      been studied and dissected with a variety of OVs such as adenovirus, herpes
      simplex virus, poxvirus, vesicular stomatitis virus, measles virus, Newcastle
      disease virus, influenza virus and reovirus, setting the molecular basis for
      further improvements in the near future. Another exciting new area of research
      has been the harnessing of naturally tumor-homing cells as carrier cells (or
      cellular vehicles) to deliver OVs to tumors. The trafficking of these tumor
      homing cells (stem cells, immune cells and cancer cells), which support
      proliferation of the viruses, is mediated by specific chemokines and cell
      adhesion molecules and we are just beginning to understand the roles of these
      molecules. Finally, we will highlight some avenues deserving further study in
      order to achieve the ultimate goals of utilizing various OVs for effective cancer
      treatment.

PMID- 18328832
TI  - Proteomic identification of differentially expressed genes in mouse neural stem
      cells and neurons differentiated from embryonic stem cells in vitro.
AB  - Embryonic stem (ES) cells are pluripotent stem cells and give rise to a variety
      of differentiated cell types including neurons. To study a molecular basis for
      differentiation from ES cells to neural cells, we searched for proteins involved
      in mouse neurogenesis from ES cells to neural stem (NS) cells and neurons by two
      dimensional gel electrophoresis (2-DE) and peptide mass fingerprinting, using
      highly homogeneous cells differentiated from ES cells in vitro. We newly
      identified seven proteins with increased expression and one protein with
      decreased expression from ES cells to NS cells, and eight proteins with decreased
      expression from NS cells to neurons. Western blot analysis confirmed that a tumor
      specific transplantation antigen, HS90B, decreased, and an extracellular matrix
      and membrane glycoprotein (such as laminin)-binding protein, galectin 1 (LEG1),
      increased in NS cells, and LEG1 and a cell adhesion receptor, laminin receptor
      (RSSA), decreased in neurons. The results of RT-PCR showed that mRNA of LEG1 was
      also up-regulated in NS cells and down-regulated in neurons, implying an
      important role of LEG1 in regulating the differentiation. The differentially
      expressed proteins identified here provide insight into the molecular basis of
      neurogenesis from ES cells to NS cells and neurons.

PMID- 18328833
TI  - Usefulness of the neutrophil to lymphocyte ratio in predicting long-term
      mortality in ST segment elevation myocardial infarction.
AB  - Neutrophil to lymphocyte ratio (N/L) has been associated with poor outcomes in
      patients who underwent cardiac angiography. Nevertheless, its role for risk
      stratification in acute coronary syndromes, specifically in patients with ST
      segment elevation myocardial infarction (STEMI), has not been elucidated. We
      sought to determine the association of N/L maximum value (N/L max) with mortality
      in the setting of STEMI and to compare its predictive ability with total white
      blood cell maximum count (WBC max). We analyzed 515 consecutive patients admitted
      with STEMI to a single university center. White blood cells (WBC) and
      differential count were measured at admission and daily for the first 96 hours
      afterward. Patients with cancer, inflammatory diseases, or premature death were
      excluded, and 470 patients were included in the final analysis. The association
      between N/L max and WBC max with mortality was assessed by Cox regression
      analysis. During follow-up, we registered 106 deaths (22.6%). A positive trend
      between mortality and N/L max quintiles was observed; 6.4%, 12.4%, 11.7%, 34%,
      and 47.9% of deaths occurred from quintiles 1 to 5 (p <0.001), respectively. In a
      multivariable setting, after adjusting for standard risk factors, patients in the
      fourth (Q4 vs Q1) and fifth quintile (Q5 vs Q1) showed the highest mortality risk
      (hazard ratio 2.58, 95% confidence interal 1.06 to 6.32, p = 0.038 and hazard
      ratio 4.20, 95% confidence interal 1.73 to 10.21, p = 0.001, respectively). When
      WBC max and cells subtypes were entered together, N/L max remained as the only
      WBC parameter; furthermore, the model with N/L max showed the most discriminative
      ability. In conclusion, N/L max is a useful marker to predict subsequent
      mortality in patients admitted for STEMI, with a superior discriminative ability
      than total WBC max.

PMID- 18328834
TI  - Comparison of Troponin T to creatine kinase and to radionuclide cardiac imaging
      infarct size in patients with ST-elevation myocardial infarction undergoing
      primary angioplasty.
AB  - Troponin is used mainly for detection of minor myocardial damage, whereas
      repeated measurements of creatine kinase (CK) and myocardial band (CK-MB) are
      used for assessing infarct size in patients with myocardial infarction. The
      purpose of this study was to correlate peak level and area under the curve (AUC)
      of troponin T to that of CK and CK-MB and with single-photon emission computed
      tomographic infarct size and left ventricular function in patients with ST
      elevation myocardial infarction. In this multicenter study (29 centers, 5
      countries), we included 267 patients who underwent primary coronary intervention
      within 6 hours of onset of symptoms. All had repeated measurements of troponin T,
      CK, and CK-MB. Infarct size and left ventricular function were assessed by single
      photon emission computed tomography performed on days 7 and 30. Mean infarct
      sizes were 14% on day 7 and 10% on day 30, and mean ejection fractions were 42%
      on day 7 and 45% on day 30 after the acute infarct. Very high correlation (r
      >0.85, Spearman correlation) was found between peak level and AUC of troponin T,
      CK, and CK-MB. Similar high correlation was found between peak level and AUC of
      troponin, CK, and CK-MB with single-photon emission computed tomographic infarct
      size (r >0.70). In conclusion, based on the results of this multicenter study, we
      suggest that peak levels and AUC of troponin are as accurate as CK and CK-MB in
      estimating myocardial infarct size.

PMID- 18328835
TI  - Effect of dietary n-3 polyunsaturated fatty acids on the inducibility of
      ventricular tachycardia in patients with ischemic cardiomyopathy.
AB  - Increased consumption of fish and/or fish oil was associated with decreased risk
      of sudden cardiac death (SCD). The study aim was to evaluate the antiarrhythmic
      effect of dietary fish oil on the inducibility of ventricular tachycardia (VT) at
      high risk of SCD. Patients with coronary artery disease undergoing defibrillator
      implantation were recruited if sustained monomorphic VT could be induced by
      programmed extra stimuli at 2 cycle lengths. After the initial study, 12 patients
      consumed 3 g/d of encapsulated fish oil for approximately 6 weeks before a
      repeated electrophysiologic study. To control for fluctuations in the
      inducibility of VT, an additional 14 patients with no dietary manipulation were
      also studied. Aggressiveness of stimulation required to induce VT was ranked from
      least aggressive to most aggressive based on cycle length and number of extra
      stimuli, with noninducibility ranked highest. At the repeated electrophysiologic
      study, in the fish-oil group, 42% had no inducible VT, 42% required more
      aggressive stimulation to induce VT, 8% required identical stimulation, and 8%
      required less stimulation compared with 7%, 36%, 36%, and 21% in the control
      group, respectively. Overall, there was a change to noninducible or less
      inducible VT in the fish-oil group, but no change in the control group (p = 0.003
      and p = 0.65, respectively; Wilcoxon's sign-rank test). In conclusion, dietary n
      3 fatty acid supplementation decreased the inducibility of VT in patients at risk
      of SCD. These findings suggest that dietary fish oil can have an antiarrhythmic
      effect.

PMID- 18328836
TI  - Usefulness of noninvasive estimate of pulmonary vascular resistance to predict
      mortality, heart failure, and adverse cardiovascular events in Patients With
      stable coronary artery disease (from the Heart and Soul Study).
AB  - Pulmonary vascular resistance (PVR) is an important hemodynamic variable that
      affects prognosis and therapy in a wide range of cardiovascular and pulmonary
      conditions. We sought to determine whether a noninvasive estimate of PVR predicts
      adverse outcomes in patients with stable coronary artery disease. Using Doppler
      echocardiography we measured the estimated PVR (defined as the ratio of the
      tricuspid regurgitant velocity [TRV] to the velocity-time integral [VTI] of the
      right ventricular outflow tract [RVOT]) in 795 ambulatory patients with stable
      coronary artery disease. Participants were categorized by quartiles of the
      TRV/VTI RVOT ratio. Hazard ratios (HRs) and 95% confidence intervals were
      calculated for all-cause mortality, heart failure hospitalization, and adverse
      cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or
      stroke). After 4.3 years of follow-up there were 161 deaths, 44 deaths from
      cardiovascular causes, 103 heart failure hospitalizations, and 120 adverse
      cardiovascular events. Compared with patients in the lowest TRV/VTI RVOT
      quartile, those in the highest quartile were at increased risk of all-cause
      mortality (unadjusted HR 1.8, 95% confidence interval 1.3 to 2.5), heart failure
      hospitalization (unadjusted HR 2.9, 95% confidence interval 2.0 to 4.3), and
      adverse cardiovascular events (unadjusted HR 2.0, 95% confidence interval 1.4 to
      2.9). After multivariate adjustment, patients in the highest quartile were at
      increased risk of heart failure hospitalizations (adjusted HR 2.5, 95% confidence
      interval 1.3 to 4.7). In conclusion, a noninvasive estimate of PVR (TRV/VTI RVOT
      ratio) predicts mortality, heart failure hospitalization, and adverse
      cardiovascular events in patients with stable coronary artery disease.

PMID- 18328837
TI  - Effects of acute mental stress and exercise on inflammatory markers in patients
      with coronary artery disease and healthy controls.
AB  - Physical and mental stressors result in increased inflammation markers in
      populations free of coronary artery disease (CAD). However, inflammatory
      responses to mental and exercise challenges have not been established in patients
      with CAD. This study investigated the responses of inflammatory markers,
      including C-reactive protein (CRP), interleukin-6 (IL-6), and soluble
      intercellular adhesion molecule-1, in patients with CAD after successful elective
      percutaneous coronary intervention (n = 36, 59 +/- 8 years of age, 33% women) and
      healthy controls without a history of CAD (n = 28, 54 +/- 10 years of age, 36%
      women). Increases in inflammatory markers were examined in response to mental
      challenge tasks (anger recall and mental arithmetic) and treadmill exercise.
      Stress echocardiography was used to rule out stress-induced ischemia as a
      possible confounding factor. Results showed that CRP increased significantly to
      mental challenge and exercise (p values <0.01), and CRP responses were higher in
      patients with CAD than in controls (change in mental arithmetic 0.19 +/- 0.11 vs
      0.01 +/- 0.03 mg/L, p = 0.003; change in exercise 0.57 +/- 0.11 vs 0.08 +/-
      0.0.03 mg/L, p = 0.001). Increased norepinephrine responses were related to
      larger CRP and IL-6 increases to mental challenge tasks (p values <0.05).
      Exercise elicited increased CRP, IL-6, and soluble intercellular adhesion
      molecule-1 levels (p values <0.01), and these responses were larger than with
      mental challenge tasks (p values <0.05). In conclusion, mental stress and
      exercise induce increased levels of inflammatory markers in patients with CAD.
      These stress-induced increases are larger than in healthy subjects, occur in the
      absence of myocardial ischemia, and are related to the neurohormonal stress
      response.

PMID- 18328838
TI  - Comparison of sensitivity, specificity, positive predictive value, and negative
      predictive value of stress testing versus 64-multislice coronary computed
      tomography angiography in predicting obstructive coronary artery disease
      diagnosed by coronary angiography.
AB  - Sixty-four-multislice coronary computed tomographic angiography (CTA) and
      coronary angiography were performed in 145 patients (mean age 67 +/- 10 years),
      and stress testing was performed in 47 of these patients to determine the
      sensitivity, specificity, positive predictive value, and negative predictive
      value of coronary CTA and of stress testing in diagnosing obstructive coronary
      artery disease (CAD) in patients with suspected CAD. In 145 patients, coronary
      CTA had 98% sensitivity, 74% specificity, 90% positive predictive value, and 94%
      negative predictive value in diagnosing obstructive CAD. In 47 patients, stress
      testing had 69% sensitivity, 36% specificity, 78% positive predictive value, and
      27% negative predictive value for diagnosing obstructive CAD, whereas coronary
      CTA had 100% sensitivity, 73% specificity, 92% positive predictive value, and
      100% negative predictive value for diagnosing obstructive CAD. In conclusion,
      coronary CTA has better sensitivity, specificity, positive predictive value, and
      negative predictive value than stress testing in diagnosing obstructive CAD.

PMID- 18328839
TI  - Effect of percutaneous coronary intervention on coronary blood flow at rest in
      myocardial sites remote from the intervention site in patients with stable angina
      pectoris.
AB  - Little is known about changes in myocardial perfusion of myocardial regions
      supplied by angiographically normal or near-normal coronary arteries after
      percutaneous coronary intervention (PCI) of the target lesion. The purpose of
      this study was to assess the effect of PCI on coronary blood flow at rest in
      sites remote from the PCI. We studied 85 patients who underwent successful
      elective PCI for stable angina. We used the Thrombolysis In Myocardial Infarction
      frame count to provide a simple continuous index of coronary flow and myocardial
      perfusion in the target and nontarget arteries. Coronary artery diameters of
      nontarget vessels did not significantly differ before and after PCI and at 6
      months' follow-up. At baseline, the greater the percent diameter stenosis in the
      target artery, the slower the flow in the target (r = 0.22, p <0.01) and
      nontarget arteries (r = 0.28, p <0.01). Relief of stenosis using PCI did not
      account for simultaneous changes in epicardial coronary blood flow of the
      nontarget artery. After 6 months, coronary blood flow improved in both the target
      (p <0.05) and nontarget arteries (p = 0.007). In conclusion, this study provided
      evidence of a functional link between coronary blood flow in diseased and
      nondiseased arteries. Relief of a significant stenosis using PCI globally
      improved regional and global myocardial blood flow at rest in patients with
      stable angina. Flow improvement was not apparent at the time of
      revascularization, but at 6 months' follow-up. Late upturn of the
      microcirculation may account for delayed recovery of myocardial perfusion.

PMID- 18328840
TI  - Impact of renal insufficiency on angiographic, procedural, and in-hospital
      outcomes following percutaneous coronary intervention.
AB  - Patients with chronic renal insufficiency (RI) have higher in-hospital mortality
      and major adverse cardiac event (MACE) rates after percutaneous coronary
      intervention (PCI). The mechanisms of this adverse course are not well
      understood. It was hypothesized that this worse outcome may be caused by
      inadequate PCI results secondary to more complex coronary anatomy in patients
      with RI. Baseline, procedural, and outcome variables of all PCI cases at the
      University Health Network are entered prospectively in the PCI Registry. All PCI
      cases between April 1, 2000, and October 31, 2005, excluding patients in shock,
      who had preprocedural creatinine clearance (CrCl) measured were included in this
      study (n = 10,821 of 11,023 patients). Moderate RI (CrCl <60 ml/min) was
      evaluated as an independent predictor of procedural outcomes, death, and MACE
      (defined as death, myocardial infarction, abrupt closure, or coronary artery
      bypass grafting). Moderate RI (CrCl <60 ml/min) independently predicted the
      procedural outcomes of worse residual stenosis >20% (p = 0.03), number of
      undeliverable stents (p = 0.003), and smallest stent diameter (p <0.001). Worst
      residual stenosis >20% and any undeliverable stent were significantly associated
      with in-hospital MACEs (odds ratio [OR] 3.97, 95% confidence interval [CI] 3.0 to
      5.3, p <0.001 and OR 1.89, 95% CI 1.2 to 2.9, p = 0.002) and mortality (OR 3.82,
      95% CI 2.2 to 6.7, p <0.001 and OR 3.0, 95% CI 1.6 to 5.9, p = 0.002). These
      risks were independent of all other measured variables. In conclusion, moderate
      to severe RI was a strong predictor of worse procedural results during PCI,
      which, in turn, were independent predictors of in-hospital MACE and mortality and
      independent contributors to the higher risk of in-hospital adverse events
      observed after PCI in patients with RI.

PMID- 18328841
TI  - Aspirin desensitization in patients undergoing percutaneous coronary
      interventions with stent implantation.
AB  - The aim of this study was to test the safety and efficacy of a novel rapid
      desensitization procedure in patients with acetylsalicylic acid sensitivity and
      coronary artery disease who underwent cardiac catheterization and coronary stent
      implantation. Aspirin plays a key role in the secondary prevention of
      atherothrombotic events and thrombotic complications after stent implantation.
      Aspirin sensitivity not only limits patients to benefit from the long-term use of
      this antiplatelet agent but is also often an impediment to the implantation of
      bare-metal and drug-eluting coronary stents. Of 1,014 patients admitted for
      cardiac catheterization, 26 (2.6%) had histories of aspirin sensitivity
      characterized by respiratory or cutaneous manifestations (none had previous
      anaphylactic reactions); of these, 61.5% presented with acute coronary syndromes.
      All patients underwent a novel rapid desensitization challenge procedure before
      cardiac catheterization, except for those presenting with ST-elevation myocardial
      infarctions (n = 4), who underwent desensitization before hospital discharge. The
      desensitization procedure involved the oral administration of 6 sequential doses
      of aspirin (1, 5, 10, 20, 40, and 100 mg) over 5.5 hours without the use of
      corticosteroids or antihistamines. Patients were followed for 1 year to assess
      compliance with aspirin therapy and adverse events. The desensitization procedure
      was successful in 23 patients (88.5%). Percutaneous coronary intervention with
      stent implantation was performed in 22 patients (1.8 stents/patient). Drug
      eluting stents were used in all patients except those who underwent primary
      percutaneous coronary intervention (n = 3), in whom bare-metal stents were used.
      Multivessel percutaneous coronary intervention was performed in 30.7% of
      patients. At follow-up, all patients who successfully responded to the
      desensitization procedure tolerated aspirin well, without developing allergic
      reactions. Aspirin was withdrawn in only 1 patient, because of a peptic ulcer. In
      conclusion, rapid desensitization is safe and highly effective in patients with
      aspirin sensitivity and coronary artery disease who undergo coronary stent
      implantation, including those who receive drug-eluting stents.

PMID- 18328842
TI  - A percutaneous coronary intervention-thrombolytic predictive instrument to assist
      choosing between immediate thrombolytic therapy versus delayed primary
      percutaneous coronary intervention for acute myocardial infarction.
AB  - Based on the thrombolytic predictive instrument (TPI), we sought to create
      electrocardiographically based, real-time decision support to immediate
      identification of patients with ST-segment elevation myocardial infarction
      (STEMI) likely to benefit from primary percutaneous coronary intervention (PCI)
      compared with thrombolysis. Using data from the Atlantic Cardiovascular Patient
      Outcomes Research Team (C-PORT) Trial, we tested a mathematical model predicting
      mortality in patients with STEMI if treated with PCI and if treated with
      thrombolytic therapy. We adapted the model for incorporation into computerized
      electrocardiograms as a PCI-TPI. For patients with STEMI in the C-PORT Trial, the
      model yielded unbiased mortality predictions: for those receiving thrombolysis,
      it predicted 6.3% mortality and actual mortality was 6.0% (95% confidence
      interval 3.0 to 10.6); for those receiving PCI, it predicted 4.5% mortality and
      actual mortality was 3.9% (95% confidence interval 1.4 to 8.2). Excellent
      discrimination was reflected by its receiver operating characteristic curve area
      of 0.86. According to the model, and validated by actual trial outcomes, 1/3 of
      subjects accounted for all the mortality benefit from PCI. In conclusion, for
      STEMI, the PCI-TPI accurately predicts mortality for treatment with PCI and with
      thrombolytic therapy. Incorporated into electrocardiogram, it may assist
      targeting PCI to those who benefit most and identifying patients before
      hospitalization for whom a receiving hospital should prepare for PCI.

PMID- 18328843
TI  - Comparison of coronary flow reserve and fractional flow reserve in patients with
      versus without diabetes mellitus and having elective percutaneous coronary
      intervention and abciximab therapy (from the PREDICT Trial).
AB  - Patients with diabetes mellitus (DM) have poor long-term outcome after
      percutaneous coronary intervention (PCI) partly because of microvascular disease
      and distal embolization. Microvascular obstruction can be assessed by measuring
      coronary flow reserve (CFR). The Prediction of CK-MB RElease During Successful
      Stenting Correlating with Indicators of Microvascular ObstruCTion (PREDICT) trial
      compared the CFR in patients with versus without DM during PCI. Patients
      undergoing elective PCI were prospectively enrolled according to diabetic (n =
      36) and nondiabetic (n = 36) status. All patients received drug-eluting stent
      with abciximab and were followed for 30-day major adverse cardiac events. CFR and
      FFR (fractional flow reserve) before and after stenting were measured before and
      after intracoronary adenosine bolus. Procedural success, MB enzyme of creatine
      kinase (CK-MB), troponin I, and high-sensitive C-reactive protein elevation,
      vascular complications, and major adverse cardiac events were not different. FFR
      before stenting was 0.77 +/- 0.03 in patients with DM versus 0.76 +/- 0.02 in
      patients without DM (p = 0.69). FFR after stenting was 0.97 +/- 0.03 and 0.99 +/-
      0.01 (p = 0.26), respectively. CFR before stenting was 1.36 +/- 0.31 in patients
      with DM versus 1.49 +/- 0.25 in patients without DM (p = 0.064). However, CFR
      after stenting was significantly lower in patients with versus without DM (1.89
      +/- 0.30 versus 2.44 +/- 0.67, p <0.001, respectively). CFR after stenting only
      moderately correlated with CK-MB and high-sensitive C-reactive protein after PCI
      but did not correlate with 30-day major adverse cardiac events. In conclusion,
      patients with DM have significantly lower CFR after stenting despite equivalent
      FFR and myonecrosis compared with patients without DM, indicating greater
      microvascular obstruction after PCI despite abciximab.

PMID- 18328844
TI  - Effectiveness of drug-eluting stent implantation for patients with unprotected
      left main coronary artery stenosis.
AB  - This study was aimed to evaluate outcomes of patients with unprotected left main
      coronary artery (LMCA) stenosis who were treated with drug-eluting stents. Sixty
      three consecutive patients with unprotected LMCA stenosis were treated with
      sirolimus-eluting stents in 52 (83%) patients and paclitaxel-eluting stents in 11
      (17%) patients, in whom percutaneous intervention was considered the sole
      alternative because of high surgical risk and/or patient preference. Urgent
      percutaneous coronary intervention within 24 hours after angiography was
      performed in 6 (10%) patients. The patients were predominantly at high surgical
      risk with 35 (56%) having EuroSCORE >6 and 39 (62%) having Parsonnet score >15.
      Involvement of the distal LMCA was observed in 46 (73%) patients. Procedural
      success was achieved in all patients. Intravascular ultrasound was used in 51
      (81%) patients. Single-stenting strategy was adopted in 36 (78%) patients with
      bifurcation stenosis. There were no death, Q-wave myocardial infarction, stent
      thrombosis, or urgent repeat revascularization events during hospitalization.
      Over a mean follow-up of 11.7 +/- 7.7 months, 18 (29%) patients experienced major
      adverse cardiac events, including 3 (5%) deaths, 7 (11%) myocardial infarctions,
      and 10 (16%) target lesion revascularizations. Stent thrombosis developed in 1
      (0.6%) patient at 35 days after the procedure. Bifurcation involvement was an
      independent predictor of major adverse cardiac events by multivariate analysis
      (hazard ratio 12.90, 95% confidence interval 1.36 to 122.45, p = 0.0259). In
      conclusion, drug-eluting stent placement for unprotected LMCA stenosis may be a
      feasible therapeutic alternative in patients at high surgical risk. However,
      bifurcation stenosis remains a significant predictor of unfavorable clinical
      outcome.

PMID- 18328845
TI  - Prognostic value of early exercise testing after coronary stent implantation.
AB  - The clinical value of early exercise stress testing (EST) after coronary stenting
      to predict long-term clinical outcomes is unknown. Of 1,000 unselected patients
      who underwent coronary stenting, 446 random patients underwent early EST the day
      after intervention. Clinical long-term outcomes (41 +/- 20 months) were
      correlated with normal (n = 314 [70%]) or positive (n = 102 [23%]) EST results.
      Patients with inconclusive test results (n = 30 [7%]) were excluded from the
      analysis. Overall mortality was significantly higher in patients with positive
      EST results (9.3% vs 3.9%, p = 0.04). Major adverse cardiac events and cardiac
      mortality also tended to be higher in patients with positive stress test results
      (45.4% vs 35.4%, p = 0.08, and 4.1% vs 1.1%, p = 0.05, respectively). Patients
      with the combination of positive stress test results and incomplete
      revascularization appeared to be the group at highest risk for major adverse
      cardiac events (47.1% vs 33.3% for patients with normal stress test results and
      complete revascularization, p = NS). Negative stress test results reduced (odds
      ratio 0.329, 95% confidence interval 0.120 to 0.905, p = 0.031) and a lower
      ejection fraction increased (odds ratio 0.942, 95% confidence interval 0.897 to
      0.989, p = 0.017) the risk for death. In conclusion, an early stress test after
      coronary stenting provides important prognostic information. Positive stress test
      results, especially in combination with incomplete revascularization, are
      associated with higher mortality, a trend toward more repeat revascularization
      procedures, and higher risk for major adverse cardiac events.

PMID- 18328846
TI  - A comparison of contemporary definitions of contrast nephropathy in patients
      undergoing percutaneous coronary intervention and a proposal for a novel
      nephropathy grading system.
AB  - Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI)
      has multiple definitions. We attempted to identify the optimal definition of CIN.
      In 985 patients undergoing PCI (derivation group), we assessed the prognostic
      significance of 4 commonly used contemporary definitions of CIN (increases in
      serum creatinine after PCI [deltaCr] >1.0 mg/dl, >0.5 mg/dl, and >25% after PCI;
      and the American College of Cardiology National Cardiovascular Data Registry
      definition) with respect to 6-month major adverse cardiovascular events (MACEs)
      and all-cause mortality (at 863 +/- 324 days). Incidence of CIN ranged widely
      (2.0% to 15%) depending on the definition used. Only 2 definitions (deltaCr >0.5
      mg/dl, >25%) consistently correlated with study outcomes. Using these 2
      definitions, we devised a new grading system (grade 0 deltaCr <or=25% and <or=0.5
      mg/dl; grade 1 deltaCr >25% but <or=0.5 mg/dl; and grade 2 deltaCr >0.5 mg/dl).
      Nephropathy grades (0 vs 1 vs 2) showed significant correlation with 6-month
      MACEs (12.4 vs 19.4 vs 28.6%, p = 0.003) and all-cause mortality (10.2 vs 10.4 vs
      40.9%, p <0.0001). In multivariate analyses, the grading system showed an
      independent association with MACEs and mortality. The prognostic value of
      nephropathy grades was prospectively confirmed in an independent validation group
      of 539 patients. In conclusion, of the 4 contemporary definitions of CIN, only
      deltaCr >25% and >0.5 mg/dl consistently predicted adverse events after PCI. By
      unifying these 2 definitions, we devised a novel nephropathy grading system that
      is predictive of 6-month MACEs and all-cause mortality after PCI.

PMID- 18328847
TI  - Usefulness of 64-detector computed tomographic angiography for diagnosing in
      stent restenosis in native coronary arteries.
AB  - The purpose of this study was to evaluate the accuracy of detector computed
      tomographic angiographic qualitative and quantitative analyses for the detection
      of in-stent restenosis (ISR) Previous studies have used qualitative analyses
      exclusively and have excluded "unevaluable" stents. Multidetector computed
      tomographic angiography (MDCT) was performed before quantitative coronary
      angiography in 67 patients with 132 stents that were evaluated by 2 techniques:
      (1) qualitative, on the basis of degree of visual hypodensity, and (2)
      quantitative, comparing in-stent with prestent Hounsfield units. All stents were
      evaluated, irrespective of image quality. The incidence of ISR was 12.5%. The
      sensitivity (94%), specificity (74%), and positive predictive value (39%) of the
      qualitative evaluation were superior to the quantitative technique (82%, 54%, and
      21%, respectively); negative predictive values were similar (99% vs 95%).
      Accuracies were equal in stents located in proximal and distal vessels. In
      conclusion, ISR can be evaluated qualitatively by 64-slice MDCT with excellent
      sensitivity and negative predictive accuracy without exclusion of unevaluable
      stents and with reasonable specificity but low positive predictive value.
      Quantitative analysis was less accurate.

PMID- 18328848
TI  - The confounded relation of coffee drinking to coronary artery disease.
AB  - After decades of conflicting studies, the relation of coffee drinking to coronary
      artery disease (CAD) risk remains unresolved. Using Cox proportional-hazards
      models with 5 covariates, 127,212 subjects who supplied baseline data at
      voluntary health examinations from 1978 to 1985 were studied. Subsequently, 8,357
      subjects were hospitalized for CAD. Coffee drinking was unrelated to CAD risk in
      58,888 never smokers, but in ex-smokers and current baseline smokers, daily
      coffee intake was associated with higher CAD risk. This disparity was generally
      consistent in stratified subgroups. In conclusion, this relation of coffee
      consumption to increased CAD risk only in smokers could be explained by
      incomplete control for smoking, by other traits of smokers, or by an adverse
      biologic interaction of a coffee ingredient with smoking effect on CAD.

PMID- 18328849
TI  - The editor's roundtable: expanded versus standard lipid panels in assessing and
      managing cardiovascular risk.

PMID- 18328850
TI  - Frequency of recurrence of atrial fibrillation within 48 hours after ablation and
      its impact on long-term outcome.
AB  - Because of delayed structural and electrophysiologic effects of radiofrequency
      ablation of atrial fibrillation (AF), early recurrence of AF after ablation does
      not necessarily indicate long-term ablation failure. This study was intended to
      assess the prognostic value of early recurrence of AF within 48 hours after
      ablation. The study included 234 patients (aged 23 to 80 years; 72% men) with
      symptomatic drug-resistant paroxysmal (n = 165) or persistent AF (n = 69) who
      underwent either Lasso-guided segmental pulmonary vein isolation (n = 83) or
      CARTO-guided left atrial circumferential ablation (n = 151). After a median
      follow-up of 12.7 months, 64% of patients with paroxysmal and 45% of patients
      with persistent AF were AF free. Early recurrence of AF occurred in 43% of
      patients and was more frequently observed in the persistent-AF group (paroxysmal
      vs persistent 39% vs 54%; p = 0.037). Early recurrence of AF was a significant
      predictor of long-term ablation failure in univariate (hazard ratio [HR] 2.29, p
      <0.001) and multivariate (HR 2.17. p <0.001) Cox regression analysis.
      Nevertheless, 46% of patients with early recurrence of AF were AF free during
      long-term follow-up compared with 68% of patients without early recurrence of AF.
      The prognostic value of early recurrence of AF was found in patients with
      paroxysmal (HR 2.05, p = 0.005) and persistent AF (HR 2.35, p = 0.013). In
      conclusion, early recurrence of AF within 48 hours after ablation was a
      significant predictor of a poor long-term ablation outcome. However, because
      nearly half the patients with early recurrence of AF remained AF free during long
      term follow-up, early recurrence of AF should not automatically result in an
      early repeated procedure.

PMID- 18328851
TI  - Frequency of helicobacter pylori seropositivity and C-reactive protein increase
      in atrial fibrillation in patients undergoing coronary angiography.
AB  - Atrial fibrillation (AF) is the most common rhythm disturbance seen in clinical
      practice. Evidence emerged that suggested inflammation was associated with risk
      of AF. Helicobacter pylori causes gastric and esophageal inflammation, as well as
      systemic and vascular inflammation. These local and systemic inflammatory effects
      may increase the risk of AF. Study patients were consecutive patients who
      underwent angiography for suspicion of coronary artery disease. Patients' AF
      status was determined by a search of hospital discharge summaries for diagnostic
      International Classification of Diseases, Ninth Revision codes for AF, assessment
      of previous electrocardiograms at the index and previous admissions to LDS
      Hospital (Salt Lake City, Utah), and search of the electrocardiographic database
      of LDS Hospital. In addition to routine laboratory studies, serum was analyzed to
      determine H pylori serostatus and index C-reactive protein (CRP) level. A total
      of 943 patients with known AF status were studied. Those with AF tended to be
      older (70.9 +/- 9.5 vs 63.9 +/- 10.7 years; p <0.001) and had a higher prevalence
      of congestive heart failure (28% vs 11%; p <0.001). In addition, patients with AF
      were more likely to be seropositive for H pylori in comparison to the
      seronegative group (65% vs 55%; p = 0.049). Mean CRP was similar between those
      with and without AF (2.2 +/- 2.7 vs 2.3 +/- 2.4 mg/dl; p = 0.79). There was no
      apparent association between H pylori serostatus and CRP. Multivariate predictors
      of AF included age (hazard ratio [HR] 1.07 per year, 95% confidence interval [CI]
      1.04 to 1.10, p <0.0001) and heart failure (HR 2.87, 95% CI 1.59 to 5.18, p
      <0.0001). H pylori added to the model was marginally associated with AF (HR 1.53,
      95% CI 0.95 to 2.47, p = 0.08) when not accounting for age. However, younger
      patients (<50 years) who were H pylori seropositive had a higher relative risk of
      AF (8%) versus those who were seronegative (0%). In comparison, older patients
      seropositive for H pylori had only a modest increased risk of AF (17.5% vs 15.4%;
      p = 0.11). In conclusion, these data showed a general association of H pylori and
      AF in patients with multiple cardiovascular risk factors. The association did not
      persist after accounting for other risk factors. Although older age was highly
      associated with AF risk in this population, H pylori was additive across 3
      distinct age groups, with the highest risk conveyed in the younger cohort.

PMID- 18328852
TI  - Frequency of spontaneous ventricular tachycardia in a pediatric population.
AB  - Few data exist on the incidence of spontaneously occurring ventricular
      tachycardia (VT) in an unselected pediatric population. The aim of this study was
      to define the incidence and outcomes of VT in a general pediatric population. A
      retrospective analysis was performed of all documented episodes of VT in children
      referred to a single center during a 10-year study period ending in December
      2005. The study center drains a stable referral area with 252,000 children aged
      <16 years, with no other pediatric cardiologic or pediatric intensive care
      services available. Twenty-seven patients with spontaneously occurring episodes
      of VT were observed, accounting for a VT incidence of 1.1 episodes/100,000
      childhood years. Thirteen patients had VT in the absence of structural heart
      disease, and 14 had VT in the presence of a wide range of underlying cardiac
      disease. Overall mortality was 5 of 27 patients (19%), but mortality was seen
      exclusively in patients with underlying heart disease; for this subgroup of
      patients, mortality was 36%. Idiopathic VT in children with structurally normal
      hearts carried a good prognosis, and treatment was required in a minority (20%)
      of these patients. In conclusion, this study highlights that VT in childhood is
      rare, and outcomes are highly dependent on the underlying pathologic substrate.

PMID- 18328853
TI  - Electrocardiographic biomarkers of ventricular repolarisation in a single family
      of short QT syndrome and the role of the Bazett correction formula.
AB  - The definition of the short QT syndrome (SQTS) is based on QT duration, but
      thorough QT- and T-wave evaluation has not been performed to date. To evaluate
      the influence of QT rate-correction formulas in SQTS diagnosis, 12-lead
      electrocardiograms (ECGs) were recorded in 27 subjects from a single family with
      SQTS. Based on QT duration corrected by Bazett formula (QTc), 4 men were
      considered to have SQTS (QTc <or=340 ms), and 16 were classified to have
      "suspected" SQTS (QT <or=320 ms and/or QTc <or=380 ms). Holter ECGs were recorded
      in the 4 patients with SQTS, 8 with suspected SQTS, and 62 healthy volunteers. We
      evaluated QT duration at each RR interval and calculated individual alpha
      coefficient of the QT/RR relation. The QT interval duration at the mean Holter
      heart rate was corrected using an individual approach and 5 "universal"
      correction formulas (Bazett, Fridericia, Sagie-Framingham, Hodges, Rautaharju).
      Patients with SQTS and controls had lower alpha coefficients of the QT/RR
      relation when compared with Bazett and Fridericia formulas. The QT rate
      dependence was lower in patients with SQTS (alpha 0.146 +/- 0.070) when compared
      with control subjects (alpha 0.203 +/- 0.039, p <0.05). The universal correction
      formulas consistently provided higher values of corrected QT interval duration at
      the mean Holter heart rate than a subject-specific correction formula (p <0.05),
      which induced false negative diagnoses. In conclusion, the Bazett correction
      formula is not appropriate for making a diagnosis of SQTS. The subject-specific
      correction formula may provide a better cut-off value definition for the
      diagnosis of SQTS.

PMID- 18328854
TI  - Mortality rates and clinical predictors of reduced survival after cardioverter
      defibrillator implantation.
AB  - We aimed to identify mortality rates and clinical predictors of reduced survival
      in a large cohort of patients after implantation of an implantable cardioverter
      defibrillator (ICD). Although existing data from clinical trials report annual
      mortality after ICD implantation from 2% to 9%, there are few data available on
      mortality rates or predictors of reduced survival in this patient population in
      clinical practice. In this single-center, retrospective analysis of 286 patients
      who underwent ICD implantation between June 1, 2000 and December 30, 2003,
      candidate predictors of mortality were assessed and subjected to multivariable
      analysis. Outcomes were documented using the Social Security Death Master File
      and hospital medical records. Overall annualized mortality was 11.3% after ICD
      implantation. Mortality rates in patients with left ventricular ejection fraction
      (LVEF) <25% were 27.2% at 1 year and 50.5% at 3 years. Digoxin (hazard ratio
      1.86, 95% confidence interval [CI] 1.21 to 2.86, p = 0.0046) and loop diuretics
      (hazard ratio 1.59, 95% CI 1.06 to 2.38, p = 0.024) were associated with reduced
      survival. Angiotensin-converting enzyme inhibitor or aldosterone receptor blocker
      use was associated with reduced mortality (hazard ratio 0.50, 95% CI 0.31 to
      0.80, p = 0.0038). In conclusion, mortality after ICD implantation is higher than
      demonstrated in primary or secondary prevention ICD trials; LVEF remains a potent
      predictor of mortality after ICD implantation, particularly in patients with an
      LVEF <25%; loop diuretic and digoxin use is associated with an approximate
      twofold increase in mortality in this population; and angiotensin-converting
      enzyme inhibitor or aldosterone receptor blocker use is associated with improved
      survival after ICD implantation.

PMID- 18328855
TI  - Analysis of randomized controlled trials on the effect of magnitude of heart rate
      reduction on clinical outcomes in patients with systolic chronic heart failure
      receiving beta-blockers.
AB  - Beta blockers improve cardiac function and prolong survival in patients with
      systolic chronic heart failure (CHF). However, the exact mechanisms underlying
      these benefits are uncertain. Specifically, it is unclear whether a close
      relation exists between heart rate (HR) reduction and clinical outcomes with
      these agents. This hypothesis was therefore tested within randomized controlled
      trials of beta blockers in systolic CHF. Left ventricular ejection fraction
      (LVEF) and HR values at baseline and study end were obtained from available beta
      blocker randomized clinical trials. The relation between change in HR and all
      cause mortality as well as the LVEF was determined using regression analysis.
      Thirty-five trials, which included 22,926 patients with a mean follow-up duration
      of 9.6 months, were analyzed for all-cause mortality, the LVEF, and HR. There was
      a close relation between all-cause annualized mortality rate and HR (adjusted R2
      = 0.51, p = 0.004). A strong correlation between change in HR and change in LVEF
      (adjusted R2 = 0.48, p = 0.000) was also observed. When only trials with >100
      patients were included, an even tighter correlation was seen (adjusted R2 = 0.60,
      p = 0.0004). In conclusion, these analyses indicate that a major contributor to
      the clinical benefits of beta-blocker therapy in systolic CHF may be the HR
      lowering effect of these agents. Therefore, the magnitude of HR reduction may be
      more important than the achievement of target dose in beta-blocker treatment of
      systolic CHF.

PMID- 18328856
TI  - Effect of pregnancy on left ventricular motion (twist) in women with aortic
      stenosis.
AB  - The combination of fixed outflow obstruction from aortic stenosis (AS) and the
      hemodynamic changes of pregnancy increased the risk of maternal or fetal
      deterioration. Left ventricular (LV) response in patients with AS to the
      hemodynamic changes of pregnancy has not been examined. We studied and compared
      myocardial mechanics with echocardiography in 3 groups of 10 women each,
      including (1) pregnant with bicuspid aortic valve (BAV; peak aortic gradient 59
      +/-7 mm Hg, aortic valve area 0.9 +/- 0.04 cm2), (2) pregnant without BAV, and
      (3) nonpregnant, healthy volunteer. Measurements in the pregnant BAV group were
      made on 3 occasions, within a year before pregnancy (baseline), in the antepartum
      period, and at least 6 weeks postpartum. Tissue tracking ultrasound was used to
      assess longitudinal strain and LV twist. During pregnancy, peak AS gradient rose
      from 59 +/- 7 to 70 +/- 9 mm Hg (p = 0.004) whereas valve area remained unchanged
      0.9 +/- 0.04 to 0.8 +/- 0.04 cm2 (p = 0.48) as compared with baseline (before
      pregnancy). Overall, in all patients, there was no significant change in the
      longitudinal strain (-22 +/- 1, -21 +/- 0.6, -20 +/- 0.6 percent, p = 0.21)] at
      baseline, during pregnancy, or after pregnancy, respectively. Patients with AS
      had a higher baseline LV twist compared with both control groups (5.4 +/- 0.3,
      pregnant, with AS; 4.1 +/- 0.8, pregnant, without AS; 3.6 +/- 0.3, nonpregnant
      volunteer; expressed in degrees; p = 0.023). Additionally, all but 2 patients had
      a significant increase in LV twist during pregnancy compared with baseline. These
      2 women had symptomatic deterioration requiring urgent aortic balloon
      valvuloplasty. Postpartum, in all AS patients, LV twist returned to antepartum
      values. In conclusion, we found that LV twist was significantly increased in
      women with congenital AS. During pregnancy, LV twist further increased in the
      antepartum period, except in those women who experienced functional
      deterioration.

PMID- 18328857
TI  - Mechanical right ventricular dyssynchrony in patients after atrial switch
      operation for transposition of the great arteries.
AB  - Recent data suggest potential benefits of cardiac resynchronization therapy in
      the management of right ventricular (RV) dysfunction in congenital heart disease.
      The aim of this study was to determine the nature, prevalence, and functional
      implications of mechanical RV dyssynchrony in patients after Senning or Mustard
      procedures for transposition of the great arteries. Twenty-eight patients (mean
      age 21.1 +/- 3.5 years) at 19.9 +/- 3.2 years after atrial switch operations and
      29 healthy controls were studied. The times from the onset of QRS to peak
      systolic strain (T epsilon) at the base of and the mid RV free wall, the
      ventricular septum (VS), and the left ventricular (LV) free wall were determined
      using tissue Doppler echocardiography. Intraventricular mechanical delay was
      defined as Delta T epsilon(RV-VS) and interventricular mechanical delay as Delta
      T epsilon(RV-LV). In patients, the magnitude of RV intra- and interventricular
      mechanical delay was correlated with cardiac magnetic resonance-derived RV
      volumes and ejection fractions (n = 26) and treadmill exercise testing parameters
      (n = 20). Compared with controls, patients had significantly longer Delta T
      epsilon(RV-VS) (48.1 +/- 50.9 vs 17.0 +/- 16.1 ms, p <0.001) and Delta T
      epsilon(RV-LV) (63.1 +/- 49.5 vs 19.0 +/- 12.9, p <0.001). Nine patients (32%)
      exhibited RV dyssynchrony (Delta T epsilon(RV-VS) >49 ms, control mean +/- 2SD),
      and 16 patients (57%) showed interventricular dyssynchrony (Delta T epsilon(RV
      LV) >45 ms). In patients, RV intra- and interventricular mechanical delay was
      correlated negatively with the RV ejection fraction (both r = -0.42, p = 0.03)
      and percentage predicted maximum oxygen consumption (r = -0.50, p = 0.03, and r =
      -0.52, p = 0.02, respectively) and positively with minute ventilation/carbon
      dioxide production slope (r = 0.49, p = 0.03, and r = 0.56, p = 0.01,
      respectively). In conclusion, RV dyssynchrony is common in young adults after
      atrial switch operations and is associated with RV systolic dysfunction and
      impaired exercise performance.

PMID- 18328858
TI  - Association of sleep-disordered breathing and ventricular arrhythmias in patients
      without heart failure.
AB  - The prevalence and characteristics of sleep-disordered breathing (SDB) in
      patients with ventricular arrhythmias, such as premature ventricular complexes
      and ventricular tachycardia, are unknown. Therefore, this study was conducted to
      evaluate the prevalence of SDB in patients with severe ventricular arrhythmias
      and normal left ventricular (LV) function. Thirty-five patients (63% men, mean
      age 57.4 +/- 13.8 years) underwent a sleep study. All patients had ventricular
      tachycardia or frequent premature ventricular complexes (>or=300/hour) and had
      been referred to the cardiology department for medication, catheter ablation
      therapy, or the implantation of a cardioverter-defibrillator. Patients with heart
      failure with LV ejection fractions <50% were excluded; in the remaining patients,
      the mean LV ejection fraction was 63.9 +/- 8.0%. Twenty-one patients (60%) had
      SDB with apnea-hypopnea indexes >or=5/hour, and the average apnea-hypopnea index
      was 22.7 +/- 17.9/hour. Twelve patients (34%) had moderate to severe SDB, with an
      average apnea-hypopnea index of 33.6 +/- 16.6/hour. Central dominant sleep apnea
      was evident in 3 patients with SDB. The average age and body mass index were
      significantly higher in patients with SDB than in those without SDB (age 62.0 +/-
      12.8 vs 50.6 +/- 12.7 years, body mass index 26.3 +/- 4.0 vs 21.2 +/- 2.0 kg/m2).
      In conclusion, this study found a high prevalence of SDB in patients with
      ventricular arrhythmias and normal LV function.

PMID- 18328859
TI  - Myths about surgical myectomy: rumors of its death have been greatly exaggerated.

PMID- 18328860
TI  - Medical data, the media, and distortion of the facts in the internet era.

PMID- 18328861
TI  - Product safety compromises patient safety (an unjustified black box warning on
      ultrasound contrast agents by the Food and Drug Administration).

PMID- 18328862
TI  - Lawrence Sorel Cohen, MD: a conversation with the editor.

PMID- 18328863
TI  - Prevention of contrast-induced nephropathy in patients undergoing emergent
      coronary procedures.

PMID- 18328864
TI  - Authors' reply to Bhindi, Testa, and vanGaal.

PMID- 18328865
TI  - Social anxiety and positive emotions: a prospective examination of a self
      regulatory model with tendencies to suppress or express emotions as a moderating
      variable.
AB  - The purpose of the present study was to examine social anxiety as a predictor of
      positive emotions using a short-term prospective design. We examined whether the
      effects of social anxiety on positive emotions are moderated by tendencies to
      openly express or suppress emotions. Over the course of a 3-month interval,
      people with excessive social anxiety endorsed stable, low levels of positive
      emotions. In addition, people with low social anxiety who frequently display
      their emotions openly, whether negative or positive, reported the greatest
      increases in positive emotions. Similar results were found when using a measure
      of emotion suppression (low social anxiety and less tendency to rely on these
      types of regulatory acts led to the greatest positive emotions). These social
      anxiety main and interactive effects could not be attributed to depressive
      symptoms. Our findings suggest that relations between social anxiety and positive
      emotional experiences over time are best understood in the context of meaningful
      individual differences such as affect regulatory strategies.

PMID- 18328866
TI  - "I need to talk about it": a qualitative analysis of trauma-exposed women's
      reasons for treatment choice.
AB  - A significant proportion of individuals suffering from posttraumatic stress
      disorder do not seek or receive effective treatment. Understanding the reasons
      why an individual chooses to seek treatment or prefers one treatment to another
      is a critical step to improve treatment seeking. To begin to understand these
      reasons, we conducted a qualitative analysis of the reasons women gave for
      choosing a cognitive-behavioral treatment, prolonged exposure (PE), or a
      pharmacological treatment, sertraline (SER). A community sample of women with
      trauma histories were asked to view standardized rationales, to choose among PE,
      SER, or no treatment, and to give 5 reasons for their choice. Women indicated
      that they were more likely to prefer the psychotherapy to the medication. Across
      reasons given, the most commonly cited reason for treatment preference
      highlighted why or how the treatment worked (e.g., I need to talk about it); and
      this reason emerged as the strongest predictor of preference for PE.
      Understanding this role of perceived treatment mechanism may aid clinicians and
      public health policy officials to identify and address help-seeking barriers
      regarding treatment.

PMID- 18328867
TI  - Acceptability of behavioral and pharmacological treatments for attention
      deficit/hyperactivity disorder: relations to child and parent characteristics.
AB  - One-hundred nine mothers of 5- to 12-year-old boys with attention
      deficit/hyperactivity disorder (ADHD) participated. Mothers read case
      descriptions of boys with ADHD and of boys with both ADHD and oppositional
      defiant disorder (ODD). Half of the mothers were randomly assigned to read
      descriptions of behavioral parent training and half to read descriptions of
      stimulant medication as treatments for the children in the case descriptions.
      Mothers rated the acceptability and effectiveness of the treatments and provided
      information on their experiences with both types of treatment. Mothers rated
      behavioral parent training as more acceptable than medication. There was no
      difference in ratings of the effectiveness of the two treatments in the
      scenarios, and mothers rated medication as more effective than behavioral
      strategies with their own children. Comorbidity of ADHD and ODD did not influence
      ratings of acceptability or effectiveness. Mothers' ratings of the acceptability
      of behavioral parent training were related to how much they believed in these
      strategies and how effective the strategies were with their own children.
      Although mothers' ratings of the acceptability of medication were related to
      their beliefs in this form of treatment, they were not related to perceptions of
      effectiveness of medication for their own child. Implications for understanding
      the difficulties faced by parents of children with ADHD in treatment decision
      making are presented.

PMID- 18328868
TI  - Randomized, controlled trial of Behavioral Family Systems Therapy for Diabetes:
      maintenance and generalization of effects on parent-adolescent communication.
AB  - We report a randomized trial of a revised Behavioral Family Systems Therapy for
      Diabetes (BFST-D) intervention. Families of 104 adolescents with diabetes were
      randomized to standard care (SC) or to 6 months of an educational support group
      (ES) or BFST-D. Family communication and problem-solving skills were assessed at
      0, 6, 12, and 18 months by independent rating of videotaped family problem
      solving discussions. BFST-D improved individual communication of adolescents and
      mothers, but not fathers. BFST-D significantly improved quality of family
      interaction compared to SC (10 of 12 comparisons) and ES (6 of 12 comparisons).
      Changes in family communication were differentially associated with changes in
      glycemic control, adherence, and family conflict. BFST-D improved family
      communication and problem solving relative to SC and modestly relative to ES.

PMID- 18328869
TI  - Rescripting early memories linked to negative images in social phobia: a pilot
      study.
AB  - Negative self-images are a maintaining factor in social phobia. A retrospective
      study (Hackmann, A., Clark, D.M., McManus, F. (2000). Recurrent images and early
      memories in social phobia. Behaviour Research and Therapy, 38, 601-610) suggested
      that the images may be linked to early memories of unpleasant social experiences.
      This preliminary study assessed the therapeutic impact of rescripting such
      memories. Patients with social phobia (N=11) attended 2 sessions, 1 week apart.
      The first was a control session in which their images and memories were discussed
      but not modified. The second was an experimental session in which cognitive
      restructuring followed by an imagery with rescripting procedure was used to
      contextualize and update the memories. No change was observed after the control
      session. The experimental session led to significant improvement in negative
      beliefs, image and memory distress and vividness, fear of negative evaluation,
      and anxiety in feared social situations. The results suggest that rescripting
      unpleasant memories linked to negative self-images may be a useful adjunct in the
      treatment of social phobia.

PMID- 18328870
TI  - The looming maladaptive style in social anxiety.
AB  - This exploratory study examined the relationship between the looming maladaptive
      style (i.e., an enduring and traitlike cognitive pattern to appraise threat as
      rapidly rising in risk, progressively worsening, or actively speeding up and
      accelerating) and three different aspects of trait social anxiety (i.e., fear of
      negative evaluation, social interaction anxiety, and public scrutiny fears) as
      well as general anxiety and depression. A large nonclinical, female-only sample
      (n=152) completed the Looming Maladaptive Style Questionnaire-II (Riskind, J. H.,
      Williams, N. L., Theodore, L. G., Chrosniak, L. D., & Cortina, J. M. (2000). The
      looming maladaptive style: Anxiety, danger, and schematic processing. Journal of
      Personality and Social Psychology, 79, 837-852), which assesses two types of
      looming vulnerability: social (i.e., looming appraisals in response to
      potentially threatening social situations) and physical (i.e., looming appraisals
      in response to potentially threatening physical stimuli). Multiple regression
      analyses indicated that social looming uniquely predicted fear of negative
      evaluation, social interaction anxiety, and public scrutiny fears, accounting for
      7%, 4%, and 3% of the variance, respectively. However, social looming did not
      predict depression. These findings support the looming model of anxiety and
      encourage further attention to the possible role of social looming as an anxiety
      specific vulnerability factor in social anxiety.

PMID- 18328871
TI  - An investigation of the relationship between cognitive reactivity and rumination.
AB  - Teasdale's (Teasdale, J.D. (1988). Cognitive vulnerability to persistent
      depression. Cognition and Emotion, 2, 247-274) differential activation hypothesis
      refers to the ease with which maladaptive cognitive processes are triggered by
      mild dysphoria as cognitive reactivity. Supporting this model is evidence of a
      differential association between sad mood and dysfunctional cognitions in
      formerly depressed and never-depressed individuals and the finding that cognitive
      reactivity predicts depression recurrence in remitted depressives. The Leiden
      Index of Depression Sensitivity-Revised (LEIDS-R; Van der Does, A.J.W., Williams,
      J.M.G. (2003). Leiden Index of Depression Sensitivity-Revised (LEIDS-R).
      Retrieved September 4, 2007, from
      http://www.dousa.nl/publications_depression.htm#LEIDS) is a recently developed
      self-report measure that provides clinicians and researchers with a time
      efficient means by which to assess cognitive reactivity. This study investigated
      the relationship between cognitive reactivity (indexed by the LEIDS-R) and
      depressive rumination in a nonclinical sample (N=324). As predicted, partial
      correlations between the LEIDS-R (subscale and Total scores) and the Ruminative
      Response Scale (RRS; Nolen-Hoeksema, S., and Morrow, J. (1991). A prospective
      study of depression and posttraumatic stress symptoms after a natural disaster:
      The 1989 Loma Prieta earthquake. Journal of Personality and Social Psychology,
      61, 115-121) were significant after controlling for current depressive symptoms.
      A subsample of participants (n=130) was administered a structured interview to
      determine current and past depression diagnostic status. Recovered depressed
      individuals scored more highly on the LEIDS-R Total and LEIDS-R Rumination
      subscale; however, the groups did not differ on the remaining subscales.
      Regression analyses indicated that (across all participants) LEIDS-R Total made a
      unique contribution to the prediction of depression over and above trait level of
      depressive rumination. Overall, the LEIDS-R is a time-efficient self-report index
      of cognitive reactivity that demonstrates promise in distinguishing recovered and
      never-depressed individuals.

PMID- 18328872
TI  - Borderline personality characteristics and treatment outcome in cognitive
      behavioral treatments for PTSD in female rape victims.
AB  - Many studies report that comorbid borderline personality pathology is associated
      with poorer outcomes in the treatment of Axis I disorders. Given the high rates
      of comorbidity between borderline personality pathology and posttraumatic stress
      disorder (PTSD), it is essential to determine whether borderline symptomatology
      affects PTSD treatment outcome. This study examined the effects of borderline
      personality characteristics (BPC) on 131 female rape victims receiving cognitive
      behavioral treatment for PTSD. Higher BPC scores were associated with greater
      pretreatment PTSD severity; however, individuals with higher levels of BPC were
      just as likely to complete treatment and also as likely to show significant
      treatment response on several outcome measures. There were no significant
      interactions between type of treatment and BPC on the outcome variables. Findings
      suggest that women with borderline pathology may be able to benefit significantly
      from cognitive-behavioral treatment for PTSD.

PMID- 18328873
TI  - A prospective test of cognitive vulnerability models of depression with
      adolescent girls.
AB  - This study sought to provide a more rigorous prospective test of two cognitive
      vulnerability models of depression with longitudinal data from 496 adolescent
      girls. Results supported the cognitive vulnerability model in that stressors
      predicted future increases in depressive symptoms and onset of clinically
      significant major depression for individuals with a negative attributional style,
      but not for those with a positive attributional style, although these effects
      were small. This model appeared to be specific to depression, in that it did not
      predict future increases in bulimia nervosa or substance abuse symptoms. In
      contrast, results did not support the integrated cognitive vulnerability self
      esteem model that asserts stressors should only predict increased depression for
      individuals with a confluence of negative attributional style and low self
      esteem, and this model did not appear to be specific to depression.

PMID- 18328874
TI  - Advancing the assessment of parent-child interactions: development of the Parent
      Instruction-Giving Game with Youngsters.
AB  - This study investigates the validity of the Parent Instruction-Giving Game with
      Youngsters (PIGGY), a newly developed direct-observation system. The PIGGY is a
      derivative of the Dyadic Parent-Child Interaction Coding System II [DPICS-II;
      Eyberg, S. M., Bessmer, J., Newcomb, K., Edwards, D., Robinson, E. (1994). Manual
      for the Dyadic Parent-Child Interaction Coding System-II. Social and Behavioral
      Sciences Documents (Ms. No. 2897)] and the Behavior Coding System [BCS; Forehand,
      R. L., McMahon, R. J. (1981). Helping the noncompliant child. New York: Guilford
      Press] and utilizes a format similar to the more structured Compliance Test
      [Roberts, M. W., Powers, S. W. (1988). The Compliance Test. Behavioral
      Assessment, 10, 375-398]. Using the PIGGY, parents provide standardized commands
      to their child (e.g., "Put the book on the table"). The parenting skills used to
      gain compliance (e.g., instruction giving, praise, discipline techniques) as well
      as child behavior (e.g., noncompliance) are coded on an observation form. In
      Study 1, 14 "noncompliant" and 14 "compliant" children and their mothers were
      selected based on parent report of child behavior. The PIGGY differentiated
      between the two groups on repeat commands, defiant child behavior, and over
      reactive parenting. Other forms of validity are also reported. In Study 2, the
      PIGGY was used to monitor the effectiveness of behavioral parent training with a
      mother and her 3-year-old daughter with oppositional-defiant disorder. Changes in
      both child and parent behavior were reflected in PIGGY scores. Overall, these
      studies suggest that the PIGGY may be valuable as both a screening tool and a
      measure of response to treatment.

PMID- 18328875
TI  - Genitourinary tract imaging. Preface.

PMID- 18328876
TI  - CT of the urinary tract: turning attention to radiation dose.
AB  - Expanding applications and uses of CT have fueled concerns about possible
      increases in the risk of radiation-induced cancer. This article reviews several
      strategies for optimizing the radiation dose necessary for adequate CT imaging of
      the urinary tract.

PMID- 18328877
TI  - Magnetic resonance nephrourography: current and developing techniques.
AB  - MR nephrourography (MRNU) makes it possible to obtain structural and functional
      data within a single imaging examination without using ionizing radiation. The
      functional data available with MRNU allows renal physiology to be examined in
      ways that were not possible previously. Coupled with the exquisite soft-tissue
      contrast provided by standard MR images, MRNU can provide a comprehensive study
      that yields critical diagnostic information on structural diseases of the kidneys
      and collecting system, including congenital and acquired diseases, and also on
      the full range of the causes of dysfunction in the transplanted kidney.

PMID- 18328878
TI  - Nuclear imaging in the genitourinary tract: recent advances and future
      directions.
AB  - For almost three decades, noninvasive radionuclide procedures for the evaluation
      of renal disease have been important components of nuclear medicine practice.
      With the introduction of new imaging agents and procedures, these techniques can
      provide valuable data on perfusion and function of individual kidneys. In
      general, these procedures are easy to perform and carry a low radiation burden
      and sedation is not required. Moreover, radionuclide imaging of the genitourinary
      tract has become an invaluable asset to clinicians in the evaluation of renal
      parenchyma and urologic abnormalities.

PMID- 18328879
TI  - Interventional uroradiology.
AB  - With advances in imaging capabilities and percutaneous instruments, many urologic
      diseases that were once managed surgically are now managed with minimally
      invasive image-guided techniques. Interventional uroradiology has evolved from
      simple renal biopsies for diagnostic confirmation, to percutaneous management of
      stones, to ablation of renal and adrenal tumors. Central to this evolution is the
      close cooperation with the urologist and nephrologist, each of whom provides
      specific skill sets and knowledge that can be used to successfully manage the
      patient. The purpose of this article is to detail the wide range of image-guided
      interventional techniques, including a discussion of indications, methods,
      success rates, and complications.

PMID- 18328880
TI  - Imaging techniques for adrenal lesion characterization.
AB  - Imaging of the adrenal gland for characterization of adrenal lesions has made
      tremendous strides and new technologies continue to evolve. This article
      highlights the anatomic and physiologic imaging principles that underpin current
      major adrenal imaging modalities and the new techniques becoming available. This
      article focuses primarily on incidental adrenal lesions, which are encountered
      more frequently with increasing use of imaging. This article concludes with a
      brief discussion of the role of adrenal biopsy, performed less frequently because
      of the success of these noninvasive adrenal imaging advances.

PMID- 18328881
TI  - Imaging of the renal donor and transplant recipient.
AB  - Renal transplant remains the mainstay of the treatment of end-stage renal
      disease. With improvement in management strategies and the diverse imaging
      options, the yearly survival of recipients with functional kidneys has improved
      significantly. This improved survival is attributed to factors such as
      immunosuppressive therapy planning in recipients, human leukocyte antigen
      matching, surgeon experience, and recipient's age. Transplantation offers the
      closest thing to a normal state if the transplanted kidney can replace the failed
      kidneys. Living-donor kidney transplants are playing a vital role in bridging the
      gap between decreased supply of, and increased demand for, kidneys for
      transplant. Early detection and characterization of complications in the
      recipient are of immense clinical relevance, allowing timely intervention to
      prevent graft failure.

PMID- 18328882
TI  - Cross-sectional imaging evaluation of renal masses.
AB  - Most renal masses are neoplastic in origin. Recent advances in cytogenetics and
      oncology continue to expand our knowledge of the genesis and biology of renal
      tumors with their attendant implications on patient management. Current state-of
      the-art CT and MR imaging technology permit improved detection and better
      characterization of renal masses. Refinements in surgical techniques and the use
      of novel ablative technologies to treat patients who have renal masses allow
      optimal management, with reduced morbidity and mortality. Elucidation of specific
      oncologic pathways in renal cell carcinomas has led to the development of
      molecularly targeted therapies. The critical role of cross-sectional imaging
      techniques in the diagnosis, surveillance, and management of patients who have
      renal masses continues to expand.

PMID- 18328883
TI  - Imaging of hematuria.
AB  - Hematuria may have a number of causes, of which the more common are urinary tract
      calculi, urinary tract infection, urinary tract neoplasms (including renal cell
      carcinoma and urothelial tumors), trauma to the urinary tract, and renal
      parenchymal disease. This article discusses the current status of imaging of
      patients suspected of having urologic causes of hematuria. The role of all
      modalities, including plain radiography, intravenous urography or excretory
      urography, retrograde pyelography, ultrasonography, and multidetector computed
      tomography (MDCT) in evaluation of these patients is discussed. The article
      highlights the current status of MDCT urography in imaging of patients with
      hematuria, and discusses various-often controversial-issues, such as optimal
      protocol design, accuracy of the technique in imaging of the urothelium, and the
      significant issue of radiation dose associated with MDCT urography.

PMID- 18328884
TI  - Imaging the male reproductive tract: current trends and future directions.
AB  - The male reproductive system encompasses several organs: the testes, ejaculatory
      ducts, seminal vesicles, prostate, and penis. The function of this system is to
      accomplish reproduction. Diagnostic imaging modalities, such as ultrasound, CT,
      MR imaging, and positron emission tomography (PET), are increasingly used to
      evaluate the male reproductive tract. The purpose of this review is to provide an
      overview of the use of imaging techniques in the male reproductive tract and to
      discuss current trends and future directions in prostate and testicular imaging.
      This review focuses on the prostate and scrotum.

PMID- 18328885
TI  - MR imaging-guided interventions in the genitourinary tract: an evolving concept.
AB  - MR imaging-guided interventions are well established in routine patient care in
      many parts of the world. There are many approaches, depending on magnet design
      and clinical need, based on MR imaging providing excellent inherent tissue
      contrast without ionizing radiation risk for patients. MR imaging-guided
      minimally invasive therapeutic procedures have advantages over conventional
      surgical procedures. In the genitourinary tract, MR imaging guidance has a role
      in tumor detection, localization, and staging and can provide accurate image
      guidance for minimally invasive procedures. The advent of molecular and metabolic
      imaging and use of higher strength magnets likely will improve diagnostic
      accuracy and allow targeted therapy to maximize disease control and minimize side
      effects.

PMID- 18328886
TI  - Clinical assessment of asthma progression in children and adults.
AB  - Asthma is a heterogeneous disorder with a variable course, characterized by
      episodes of cough, wheezing and shortness of breath, reversible airflow
      limitation, and bronchial hyperresponsiveness. It begins early in life in many
      subjects with intermittent symptoms occurring with viral respiratory tract
      infections. Over time, and in genetically susceptible children (those with an
      atopic predisposition), the disease becomes more persistent with symptoms
      occurring in the absence of respiratory tract infections. Children with
      persistent wheezing are eventually diagnosed with asthma, with those at greatest
      risk having developed allergic sensitization early in life. Among children with
      asthma, some will have lifelong asthma with active symptoms and progressive loss
      of lung function over time, whereas other children will undergo asthma remission
      in adolescence. Once in remission, the disease may remain quiescent, or it may
      relapse in midadult life. This review focuses on studies that have enhanced our
      understanding of the progression of asthma from infancy to adulthood. Studies
      evaluating progressive loss of lung function, the best-studied measure of asthma
      progression, are also reviewed, followed by a brief discussion of whether asthma
      progression can be modified by inhaled glucocorticoid therapy.

PMID- 18328888
TI  - Interpatient variability in rates of asthma progression: can genetics provide an
      answer?
AB  - Asthma is a heterogeneous disorder with a variable natural history. In children 3
      patterns of the natural history of asthma have been described: early onset but
      transient, persistent, and later onset, with only the former leading to
      persistent asthma later in childhood. In adults a range of different asthma
      phenotypes differing in their environmental, inflammatory, and prognostic
      characteristics have also been described. These extend beyond allergic
      (extrinsic) and nonallergic (intrinsic) asthma to include persistent airflow
      obstruction and accelerated decrease in lung function over time. Asthma
      progression can be defined as the change in an individual's phenotype along a
      continuum ranging from nonasthmatic to asthmatic and subsequent development of
      severe chronic disease. It is clear that for prevention of asthma progression in
      patients, there is a need for both better understanding of the pathophysiology of
      asthma and identification of predictors of progression. Interpatient genetic
      variability has been shown to affect multiple facets of asthma progression,
      including increased susceptibility to atopy and subsequent asthma, progression to
      severe disease, and modification of the response to treatment. Thus genetic
      testing might provide a means for predicting the likely progression of an
      individual along the continuum, allowing targeting of preventative treatment.
      However, the prospect of the use of genetic information in clinical practice
      raises important social and ethical issues that will need to be addressed before
      genetic testing can be used to inform the preventative treatment of patients to
      prevent the development of progression of asthma in individuals.

PMID- 18328887
TI  - Immunologic and inflammatory mechanisms that drive asthma progression to
      remodeling.
AB  - Although histologic features of airway remodeling have been well characterized in
      asthma, the immunologic and inflammatory mechanisms that drive progression of
      asthma to remodeling are still incompletely understood. Conceptually, airway
      remodeling may be a result of persistent inflammation and/or aberrant tissue
      repair mechanisms. It is likely that several immune and inflammatory cell types
      and mediators are involved in mediating airway remodeling. In addition, different
      features of airway remodeling are likely mediated by different inflammatory
      pathways. Several important candidate mediators of remodeling have been
      identified, including TGF-beta and T(H)2 cytokines (including IL-5 and IL-13), as
      well as vascular endothelial growth factor, a disintegrin and metalloproteinase
      33, and matrix metalloproteinase 9. Mouse models of airway remodeling have
      provided important insight into potential mechanisms by which TGF-beta activation
      of the Smad-2/3 signaling pathway may contribute to airway remodeling. Human
      studies have demonstrated that anti-IL-5 reduces levels of airway eosinophils
      expressing TGF-beta, as well as levels of airway remodeling as assessed by
      bronchial biopsies. Further such studies confirming these observations, as well
      as alternate studies targeting additional individual cell types, cytokines, and
      mediators, are needed in human subjects with asthma to determine the role of
      candidate mediators of inflammation on the development and progression of airway
      remodeling.

PMID- 18328890
TI  - Natural history of asthma: persistence versus progression-does the beginning
      predict the end?
AB  - Environmental exposures during the early years and airway obstruction that
      develops during this time, in conjunction with genetic susceptibility, are
      important factors in the development of persistent asthma in childhood.
      Established risk factors for childhood asthma include frequent wheezing during
      the first 3 years, a parental history of asthma, a history of eczema, allergic
      rhinitis, wheezing apart from colds, and peripheral blood eosinophilia, as well
      as allergic sensitization to aeroallergens and certain foods. Risk factors for
      the development of asthma in adulthood remain ill defined. Moreover, reasons for
      variability in the clinical course of asthma--persistence in some individuals and
      progression in others--remain an enigma. The distinction between disease
      persistence and disease progression suggests that these are different entities or
      phenotypes. There is currently no consensus on whether disease progression
      requires either airway inflammation or airway remodeling or the combination of
      the two. For patients with irreversible airway obstruction, inflammation might,
      in part, be necessary but perhaps not entirely sufficient to induce the
      irreversible component, some of which could be attributed to alterations in the
      structure of the bronchial wall. Intervening with intermittent or daily inhaled
      corticosteroids in high-risk infants and children does not prevent disease
      progression or impaired lung growth. These findings, however, might not apply to
      adults, and further study in adults is needed to determine the effect of inhaled
      corticosteroid therapy on disease progression.

PMID- 18328889
TI  - Usefulness and optimization of mouse models of allergic airway disease.

PMID- 18328892
TI  - Sensitization does not develop in utero.
AB  - BACKGROUND: Intrauterine sensitization has been suggested to play a role in the
      development of atopic disease in children, and this has led to current guidelines
      recommending allergen avoidance during pregnancy. OBJECTIVE: To investigate the
      relevance of allergen-specific IgE in cord blood to sensitization in early
      infancy and the origin of such IgE. METHODS: Inhalant and food allergen-specific
      IgE in cord blood was analyzed and compared with specific IgE in infant blood at
      6 months of age and in parental blood. Cord blood IgA was measured to detect
      maternal blood contamination of cord blood. RESULTS: Allergen-specific IgE,
      primarily against inhalant allergens, was detected in 14% of cord blood samples.
      However, corresponding specific IgE was not found in infant blood at 6 months of
      age. Specific IgE in cord blood completely matched specific IgE in maternal blood
      with respect to allergen specificity, level of specific IgE, and ratio of total
      IgE/specific IgE. Finally, there was a correlation between specific IgE and IgA
      in cord blood. CONCLUSION: Allergen-specific IgE in cord blood does not reflect
      intrauterine sensitization but seems to be the result of transfer of maternal IgE
      to the fetus.

PMID- 18328893
TI  - Increased activation-induced cell death of high IFN-gamma-producing T(H)1 cells
      as a mechanism of T(H)2 predominance in atopic diseases.
AB  - BACKGROUND: A dysregulated and T(H)2-biased immune response appears to be a key
      pathogenetic factor in atopic diseases. Increased activation and massive
      infiltration of T cells in the dermis without any evidence for the expansion of
      their numbers in peripheral blood characterize atopic dermatitis. OBJECTIVE: To
      investigate differences and mechanisms of T(H)1 and T(H)2 cell activation-induced
      cell death (AICD) in atopic disease. METHODS: Naive (CD4(+)CD45(+)RA) and memory
      (CD4(+)CD45(+)RO) T cells were isolated from healthy and atopic individuals.
      T(H)1 and T(H)2 subsets were in vitro differentiated. High IFN-gamma-producing T
      cells and CXCR3(+) T cells were purified, and AICD of isolated cells was
      determined in addition to expression of apoptosis receptors and caspase
      activation. RESULTS: T(H)1 cells, particularly their high IFN-gamma-producing
      fraction, and CXCR3(+) T cells showed significantly increased apoptosis in atopic
      individuals. During their in vitro differentiation, both T(H)1 and T(H)2 cells of
      atopic individuals showed increased apoptosis compared with the healthy control
      group, with a significantly high apoptosis in T(H)1 cells. Increased expression
      of Fas, Fas-ligand, tumor necrosis factor receptor-II, and caspase activation was
      detected on T(H)1 cells that underwent apoptosis. Neutralization experiments
      demonstrated a dominant role of IFN-gamma and Fas-Fas-ligand interaction-mediated
      suicide in T(H)1 cell AICD. CONCLUSION: Predominant T(H)2 profile in atopic
      diseases might be a result of the increased tendency to activation and apoptosis
      of high IFN-gamma-producing T(H)1 cells.

PMID- 18328894
TI  - Increased sputum and bronchial biopsy IL-13 expression in severe asthma.
AB  - BACKGROUND: The importance of IL-13 in the asthma paradigm is supported by
      increased expression in human subjects, particularly in patients with mild-to
      moderate asthma. However, the role of IL-13 in severe asthma needs to be further
      defined. OBJECTIVE: We sought to assess IL-13 expression in sputum and bronchial
      biopsy specimens from subjects with mild-to-severe asthma. METHODS: Sputum IL-13
      concentrations were measured in 32 control subjects, 34 subjects with mild
      asthma, 21 subjects with moderate asthma, and 26 subjects with severe asthma.
      Enumeration of mast cells, eosinophils, and IL-13+ cells in the bronchial
      submucosa and airway smooth muscle (ASM) bundle was performed in 7 control
      subjects, 14 subjects with mild asthma, 7 subjects with moderate asthma, and 7
      subjects with severe asthma. RESULTS: The proportion of subjects with measurable
      IL-13 in the sputum was increased in the mild asthma group (15/34) and severe
      asthma group (10/26) compared with that seen in the control group (4/32; P =
      .004). IL-13+ cells were increased within the submucosa in all asthma severity
      groups compared with control subjects (P = .006). The number of IL-13+ cells were
      increased within the ASM bundle in the severe asthma group compared with that
      seen in the other groups (P < .05). Asthma control questionnaire scores
      positively correlated with sputum IL-13 concentrations (R(s) = 0.35, P = .04) and
      mast cells in the ASM bundle (R(s) = 0.7, P = .007). IL-13+ cells within the
      submucosa and ASM correlated with sputum eosinophilia (R(s) = 0.4, P < or = .05).
      CONCLUSIONS: IL-13 overexpression in sputum and bronchial biopsy specimens is a
      feature of severe asthma.

PMID- 18328895
TI  - The economic effect of the hydrofluoroalkane albuterol transition on children
      with asthma.

PMID- 18328896
TI  - Recall antigen reactions in patients with atopic dermatitis treated with
      tacrolimus ointment for 1 year.

PMID- 18328897
TI  - Relationship between total and specific IgE in patients with asthma from Siberia.

PMID- 18328898
TI  - Vitamin D deficiency and asthma: not a strong link--yet.

PMID- 18328900
TI  - Omalizumab also successful in chronic urticaria.

PMID- 18328902
TI  - Delayed allergic reactions to omalizumab: are patients reporting all cases?

PMID- 18328904
TI  - Blocking asthmatic progression and chronicity in the pre-corticosteroid era.

PMID- 18328905
TI  - Clinical knowledge: from access to action.

PMID- 18328906
TI  - Yellow fever preparedness.

PMID- 18328907
TI  - Paediatric palliative care.

PMID- 18328908
TI  - Long-term outcome for very preterm infants.

PMID- 18328909
TI  - Vaccination against high blood pressure: a new strategy.

PMID- 18328910
TI  - Conditional cash transfer: a magic bullet for health?

PMID- 18328911
TI  - Fast-track colorectal surgery.

PMID- 18328912
TI  - The Philippine breastfeeding struggle continues.

PMID- 18328913
TI  - Getting nuclear-bomb fuel out of radiopharmaceuticals.

PMID- 18328914
TI  - Hydrophobia phobia as social history.

PMID- 18328916
TI  - Family planning.

PMID- 18328917
TI  - Pramilla Senanayake.

PMID- 18328919
TI  - Association between venous and arterial thrombosis.

PMID- 18328920
TI  - Association between venous and arterial thrombosis.

PMID- 18328921
TI  - Global health research: don't ignore achievements so far.

PMID- 18328922
TI  - Clostridium difficile and chlorine-releasing disinfectants.

PMID- 18328923
TI  - Maternal mortality ratio for Bangladesh.

PMID- 18328925
TI  - Medicine of the person: the lost art of medicine.

PMID- 18328926
TI  - Medicine of the person: the lost art of medicine.

PMID- 18328927
TI  - Medicine of the person: the lost art of medicine.

PMID- 18328928
TI  - Neurodevelopmental disabilities and special care of 5-year-old children born
      before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study.
AB  - BACKGROUND: The increasing survival rates of children who are born very preterm
      raise issues about the risks of neurological disabilities and cognitive
      dysfunction. We aimed to investigate neurodevelopmental outcome and use of
      special health care at 5 years of age in a population-based cohort of very
      preterm children. METHODS: We included all 2901 livebirths between 22 and 32
      completed weeks of gestation from nine regions in France in Jan 1-Dec 31, 1997,
      and a reference group of 667 children from the same regions born at 39-40 weeks
      of gestation. At 5 years of age, children had a medical examination and a
      cognitive assessment with the Kaufman assessment battery for children (K-ABC),
      with scores on the mental processing composite (MPC) scale recorded. Data for
      health-care use were collected from parents. Severe disability was defined as non
      ambulatory cerebral palsy, MPC score less than 55, or severe visual or hearing
      deficiency; moderate deficiency as cerebral palsy walking with aid or MPC score
      of 55-69; and minor disability as cerebral palsy walking without aid, MPC score
      of 70-84, or visual deficit (<3/10 for one eye). FINDINGS: In total, 1817 (77%)
      of the 2357 surviving children born very preterm had a medical assessment at 5
      years and 396 (60%) of 664 in the reference group. Cerebral palsy was diagnosed
      in 159 (9%) of children born very preterm. Scores for MPC were available for 1534
      children born very preterm: 503 (32%) had an MPC score less than 85 and 182 (12%)
      had an MPC score less than 70. Of the 320 children in the reference group, the
      corresponding values were 37 (12%) and 11 (3%), respectively. In the very preterm
      group, 83 (5%) had severe disability, 155 (9%) moderate disability, and 398 (25%)
      minor disability. Disability was highest in children born at 24-28 completed
      weeks of gestation (195 children [49%]), but the absolute number of children with
      disabilities was higher for children born at 29-32 weeks (441 children [36%]).
      Special health-care resources were used by 188 (42%) of children born at 24-28
      weeks and 424 (31%) born at 29-32 weeks, compared with only 63 (16%) of those
      born at 39-40 weeks. INTERPRETATION: In children who are born very preterm,
      cognitive and neuromotor impairments at 5 years of age increase with decreasing
      gestational age. Many of these children need a high level of specialised care.
      Prevention of the learning disabilities associated with cognitive deficiencies in
      this group is an important goal for modern perinatal care for children who are
      born very preterm and for their families.

PMID- 18328929
TI  - Effect of immunisation against angiotensin II with CYT006-AngQb on ambulatory
      blood pressure: a double-blind, randomised, placebo-controlled phase IIa study.
AB  - BACKGROUND: Hypertension can be controlled adequately with existing drugs such as
      angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.
      Nevertheless, treatment success is often restricted by patients not adhering to
      treatment. Immunisation against angiotensin II could solve this problem. We
      investigated the safety and efficacy of CYT006-AngQb-a vaccine based on a virus
      like particle-that targets angiotensin II to reduce ambulatory blood pressure.
      METHODS: In this multicentre, double-blind, randomised, placebo-controlled phase
      IIa trial, 72 patients with mild-to-moderate hypertension were randomly assigned
      with a computer-generated randomisation list to receive subcutaneous injections
      of either 100 mug CYT006-AngQb (n=24), 300 mug CYT006-AngQb (24), or placebo
      (24), at weeks 0, 4, and 12. 24-h ambulatory blood pressure was measured before
      treatment and at week 14. The primary outcomes were safety and tolerability.
      Analyses were done by intention to treat. This study is registered with
      ClinicalTrials.gov, number NCT00500786. FINDINGS: Two patients in the 100 mug
      group, three in the 300 mug group, and none in the placebo group discontinued
      study treatment. All patients were included in safety analyses; efficacy analyses
      did not include the five dropouts, for whom no data were available at week 14.
      Five serious adverse events were reported (two in the 100 mug group, two in the
      300 mug group, and one in the placebo group); none were deemed to be treatment
      related. Most side-effects were mild, transient reactions at the injection site.
      Mild, transient influenza-like symptoms were seen in three patients in the 100
      mug group, seven in the 300 mug group, and none in the placebo group. In the 300
      mug group, there was a reduction from baseline in mean ambulatory daytime blood
      pressure at week 14 by -9.0/-4.0 mm Hg compared with placebo (p=0.015 for
      systolic and 0.064 for diastolic). The 300 mug dose reduced the early morning
      blood-pressure surge compared with placebo (change at 0800 h -25/-13 mm Hg;
      p<0.0001 for systolic, p=0.0035 for diastolic). INTERPRETATION: Immunisation with
      CYT006-AngQb was associated with no serious adverse events; most observed adverse
      events were consistent with local or systemic responses similar to those seen
      with other vaccines. The 300 mug dose reduced blood pressure in patients with
      mild-to-moderate hypertension during the daytime, especially in the early
      morning. FUNDING: Cytos Biotechnology AG.

PMID- 18328930
TI  - Role of cash in conditional cash transfer programmes for child health, growth,
      and development: an analysis of Mexico's Oportunidades.
AB  - BACKGROUND: Many governments have implemented conditional cash transfer (CCT)
      programmes with the goal of improving options for poor families through
      interventions in health, nutrition, and education. Families enrolled in CCT
      programmes receive cash in exchange for complying with certain conditions:
      preventive health requirements and nutrition supplementation, education, and
      monitoring designed to improve health outcomes and promote positive behaviour
      change. Our aim was to disaggregate the effects of cash transfer from those of
      other programme components. METHODS: In an intervention that began in 1998 in
      Mexico, low-income communities (n=506) were randomly assigned to be enrolled in a
      CCT programme (Oportunidades, formerly Progresa) immediately or 18 months later.
      In 2003, children (n=2449) aged 24-68 months who had been enrolled in the
      programme their entire lives were assessed for a wide variety of outcomes. We
      used linear and logistic regression to determine the effect size for each outcome
      that is associated with a doubling of cash transfers while controlling for a wide
      range of covariates, including measures of household socioeconomic status.
      FINDINGS: A doubling of cash transfers was associated with higher height-for-age
      Z score (beta 0.20, 95% CI 0.09-0.30; p<0.0001), lower prevalence of stunting (
      0.10, -0.16 to -0.05; p<0.0001), lower body-mass index for age percentile (-2.85,
      -5.54 to -0.15; p=0.04), and lower prevalence of being overweight (-0.08, -0.13
      to -0.03; p=0.001). A doubling of cash transfers was also associated with
      children doing better on a scale of motor development, three scales of cognitive
      development, and with receptive language. INTERPRETATION: Our results suggest
      that the cash transfer component of Oportunidades is associated with better
      outcomes in child health, growth, and development.

PMID- 18328932
TI  - Global action on health systems: a proposal for the Toyako G8 summit.

PMID- 18328933
TI  - Woke up paralysed--without injury or stroke.

PMID- 18328931
TI  - Liver cirrhosis.
AB  - Cirrhosis is defined as the histological development of regenerative nodules
      surrounded by fibrous bands in response to chronic liver injury, which leads to
      portal hypertension and end-stage liver disease. Recent advances in the
      understanding of the natural history and pathophysiology of cirrhosis, and in
      treatment of its complications, have resulted in improved management, quality of
      life, and life expectancy of patients. Liver transplantation remains the only
      curative option for a selected group of patients, but pharmacological treatments
      that can halt progression to decompensated cirrhosis or even reverse cirrhosis
      are currently being developed. This Seminar focuses on the diagnosis,
      complications, and management of cirrhosis, and new clinical and scientific
      developments.

PMID- 18328934
TI  - Highlights of the basic components of evidence-based practice.
AB  - This editorial provides a brief review of the basic components of evidence-based
      practice.

PMID- 18328935
TI  - Predictors of adverse events following chiropractic care for patients with neck
      pain.
AB  - OBJECTIVE: This study examines which variables may predict adverse events in
      subjects undergoing chiropractic treatment for neck pain. METHODS: This was a
      prospective, multi-center, cohort study. All new patients, 18 to 65 years of age
      with neck pain of any duration, who had not undergone chiropractic care or manual
      therapy in the prior 3 months, were eligible. Sources of data were questionnaires
      administered during the first 3 treatments. In all, 60 putative prognostic
      variables were examined, including descriptors of the patient, chiropractor, and
      type of treatment delivered. Adverse events were defined as either a new
      complaint, or the worsening of an existing complaint by more than 30% on an 11
      point numerical rating scale. Multivariate random coefficients logistic
      regression analyses were conducted to determine predictors for the following
      outcome variables: (1) any adverse event after any of the first 3 visits, (2) any
      type of adverse event after the first visit only, and (3) specific types of
      adverse events after the first visit only (ie, headache, increased neck pain,
      pain and/or stiffness at the treated area). RESULTS: In total, 579 patients were
      recruited, of whom 529 fulfilled the inclusion criteria. The reported use of a
      manipulative technique involving cervical rotation, and working status of the
      patient (sick leave or workers' compensation) were moderately associated with an
      adverse event after any of the first 3 visits. Patients who had visited their
      general practitioner in the 6 months before treatment, however, were less likely
      to have an adverse event. A longer duration with neck pain in the preceding year
      was moderately associated with specific types of events after the first visit,
      namely, headache or worsening of the presenting neck pain. Increased neck pain
      after the first visit was the easiest outcome variable to predict (area under the
      curve, 0.88; 95% confidence interval, 0.84-0.91). CONCLUSIONS: Of the 60
      independent variables examined, only 4 were found to be predictive of adverse
      events after chiropractic treatment for neck pain, one of which was found to be
      protective. The chiropractic practitioner can identify 3 of these variables
      before initiating treatment.

PMID- 18328936
TI  - Economic and resource status of the chiropractic profession in Ontario, Canada: a
      challenge or an opportunity.
AB  - OBJECTIVE: Chiropractic is one of the most frequently sought nonphysician
      provider groups. Despite its apparent recognition, the profession faces numerous
      challenges, including the economic reality of an increasing supply within a
      market of questionable demand. This paper evaluates the chiropractic manpower
      status in Ontario, Canada. METHODS: Data collected from administrative and
      education databases, insurance billing data, and population health survey data
      between 1990 and 2004 were analyzed. RESULTS: Between 1990 and 2004, the total
      number of chiropractic registrants in Ontario doubled, with an average annual
      rate of growth of about 5.4%; however, recent data suggest that the number of
      nonpracticing chiropractors is increasing, whereas the number of new registrants
      is decreasing. The rate of applications to a chiropractic institution rose
      sharply and peaked in 1996-1997, thereafter declining but leveling off in 2002
      2003. Despite the continued growth in the number of practicing chiropractors, the
      utilization of chiropractic services among the Ontario population has remained
      relatively stable, resulting in a decline in the average net annual incomes
      adjusted for inflation to 2002 dollars. CONCLUSIONS: Our results support previous
      reports projecting an oversupply of chiropractors and suggest that the
      chiropractic profession in Ontario is in long-run oversupply. Competition from
      other providers, changing population demographics, and the recent loss of public
      funding for services may present significant future challenges to current
      practitioners. Opportunities related to participation in multidisciplinary
      environments and accessing unmet population health needs may contribute to
      influencing the demand for chiropractic services. A concerted effort by
      professional and educational institutions is required.

PMID- 18328937
TI  - Altered sensorimotor integration with cervical spine manipulation.
AB  - OBJECTIVE: This study investigates changes in the intrinsic inhibitory and
      facilitatory interactions within the sensorimotor cortex subsequent to a single
      session of cervical spine manipulation using single- and paired-pulse
      transcranial magnetic stimulation protocols. METHOD: Twelve subjects with a
      history of reoccurring neck pain participated in this study. Short interval
      intracortical inhibition, short interval intracortical facilitation (SICF), motor
      evoked potentials, and cortical silent periods (CSPs) were recorded from the
      abductor pollicis brevis and the extensor indices proprios muscles of the
      dominant limb after single- and paired-pulse transcranial magnetic stimulation of
      the contralateral motor cortex. The experimental measures were recorded before
      and after spinal manipulation of dysfunctional cervical joints, and on a
      different day after passive head movement. To assess spinal excitability, F wave
      persistence and amplitudes were recorded after median nerve stimulation at the
      wrist. RESULTS: After cervical manipulations, there was an increase in SICF, a
      decrease in short interval intracortical inhibition, and a shortening of the CSP
      in abductor pollicis brevis. The opposite effect was observed in extensor indices
      proprios, with a decrease in SICF and a lengthening of the CSP. No motor evoked
      potentials or F wave response alterations were observed, and no changes were
      observed after the control condition. CONCLUSION: Spinal manipulation of
      dysfunctional cervical joints may alter specific central corticomotor
      facilitatory and inhibitory neural processing and cortical motor control of 2
      upper limb muscles in a muscle-specific manner. This suggests that spinal
      manipulation may alter sensorimotor integration. These findings may help
      elucidate mechanisms responsible for the effective relief of pain and restoration
      of functional ability documented after spinal manipulation.

PMID- 18328938
TI  - Pain perception in patients with intermittent low back pain.
AB  - OBJECTIVE: This study investigates if patients with intermittent low back pain
      (LBP) have a permanently increased pain perception between attacks. METHODS: A
      case-controlled study was performed in a university laboratory. Sixteen patients
      with intermittent LBP in a pain-free phase were recruited from 3 chiropractic
      practices. These 16 patients were compared with an age- and sex-matched symptom
      free control group, who had never had persistent pain syndromes, by applying a
      standardized algometer stimulus to 8 points on the body and registering the
      subjects' perceived pain on a 100-mm visual analog pain scale. RESULTS: No
      differences in pain perception were found between the 2 groups. CONCLUSION:
      Patients with intermittent LBP do not seem to have an altered pain perception
      between attacks, with the possible exception of facilitation on a local segmental
      spinal cord level.

PMID- 18328939
TI  - Pregnancy-related pelvic girdle pain: intertester reliability of 3 tests to
      determine asymmetric mobility of the sacroiliac joints.
AB  - OBJECTIVE: Several tests have been developed to determine the extent of
      sacroiliac asymmetry during pregnancy-related pelvic girdle pain (PGP). This
      blinded control study investigated the intertester reliability of 3 such tests
      used in PGP. METHODS: A total of 62 women (ages 20-40 years) were recruited from
      regional obstetric practices and subsequently divided into 3 groups: (1) 20 women
      without PGP who were pregnant for more than 20 weeks, (2) 22 women with PGP who
      were pregnant for more than 20 weeks, and (3) a control group of 20 women who
      were not pregnant and had no back pain or PGP. All tests were performed by 2
      physiotherapists independently of each other and blinded to each other's results.
      The 3 tests were the thumb-posterior superior iliac spines test, the heel-bank
      test, and the abduction test. RESULTS: To determine the level of agreement
      between the 2 testers, kappa values were calculated. The overall kappa is 0.30
      (range, -0.22 to 0.83), which is considered as a poor agreement. The percentage
      agreement per test/category ranged from 45% to 95%. CONCLUSION: This study of 3
      tests used to determine asymmetry of the sacroiliac joints in women with
      pregnancy-related PGP showed them to have a poor intertester reliability.

PMID- 18328940
TI  - Upright static pelvic posture as rotations and translations in 3-dimensional from
      three 2-dimensional digital images: validation of a computerized analysis.
AB  - PURPOSE: The aim of this study was to determine the accuracy in measuring the
      pelvic orientations of a phantom model using the PosturePrint method. METHODS: In
      the Universite du Quebec a Trois-Rivieres biomechanics laboratory, Trois
      Rivieres, Quebec, Canada, a mannequin was fixed on a rotating platform. For a set
      of 3 photographs (left lateral, anterior to posterior, right lateral) of each
      position, the mannequin pelvis was placed in 68 different postures on a stand, 61
      cm from a wall, in front of a digital camera. The camera was at 83.8 cm in height
      and at 3.35 m from a calibrated wall grid. Mannequin postures were in 5 degrees
      of freedom: lateral translation (Tx), lateral flexion (Rz), axial rotation (Ry),
      flexion-extension (Rx), and anterior-posterior translation (Tz). Average errors
      were the differences of the positioned postures to the PosturePrint computed
      values. RESULTS: Mean and SD of computational errors for rotation displacements
      were Rx = 0.5 degrees +/- 0.8 degrees , Ry = 1.3 degrees +/- 0.8 degrees , and Rz
      = 0.5 degrees +/- 0.3 degrees , and for translation, Tz = 1.2 +/- 0.6 mm and Tx =
      0.9 +/- 0.5 mm. CONCLUSIONS: The PosturePrint system allowed for accurate
      postural measurement of rotations and translations of a mannequin pelvis. The
      next step in evaluation of this product would be a reliability study on human
      subjects.

PMID- 18328941
TI  - Chiropractic treatment of upper extremity conditions: a systematic review.
AB  - OBJECTIVE: This study investigates the scope, type, and quality of chiropractic
      research conducted on the management of upper limb peripheral conditions. METHOD:
      A literature search regarding upper limb and chiropractic treatment was performed
      on CINAHL, MEDLINE, and MANTIS databases. Search terms included chiropractic,
      shoulder, elbow, wrist, hand, forearm, and arm, with MeSH terms for each region.
      For articles to be considered relevant, there had to be a peripheral diagnosis
      and chiropractic intervention. Papers were excluded if pain was referred from
      spinal sites. Duplicates, articles published in non-peer-reviewed literature,
      conference proceedings, grand rounds, and discussion papers where no treatment
      was actually rendered were also removed. The articles were then reviewed and
      assessed for quality using the Physiology Evidence Database (PEDro) scale.
      RESULTS: There was a total of 64 articles found. There were 36 case reports for
      the shoulder, 8 case reports for the elbow, 14 case reports for the wrist/hand,
      and 6 clinical trials (3 shoulder, 1 elbow 2 wrist). For the PEDro score, 58 case
      reports scored 0, 1 clinical trial scored 7, 2 clinical trials scored 6, 2
      clinical trials scored 4, and 1 clinical trial scored 0. CONCLUSION: There is a
      small amount of chiropractic research into upper limb conditions that is
      comprised mostly of case studies (level 4 evidence) and a small number of higher
      level publications (level 1-3 evidence). Most treatments are multimodal in
      nature, which address both spinal and peripheral structures, with joint and soft
      tissue methods. There is a need for future research to be directed at higher
      level evidence, in particular, randomized controlled trials for the chiropractic
      treatment of upper limb conditions.

PMID- 18328942
TI  - Bilateral isthmic L3 spondylolisthesis in an adult female.
AB  - OBJECTIVE: The purpose of this study is to describe an incidental finding of
      bilateral isthmic L3 spondylolysis in an adult female. CLINICAL FEATURES: A 26
      year-old woman with sickle cell anemia was involved in a motor vehicle accident.
      Lumbar radiographs were reported normal. Computed tomography scan showed
      bilateral L3 spondylolysis of the pars interarticularis. INTERVENTIONS AND
      OUTCOMES: On the basis of the normal results of physical and neurologic
      examinations, the spondylolysis was considered to be an incidental finding.
      CONCLUSIONS: L3 spondylolysis is described very rarely in the literature.
      According to the unique features of L3 in the lumbar spine, which include its
      relatively horizontal position and its equal anterior and posterior diameters, we
      suggest that mechanical shearing forces may be less effective in causing
      spondylolysis in this area. This case is more suggestive of congenital and
      genetic causes as the contributing factors of spondylolysis.

PMID- 18328943
TI  - Osteosarcoma of the hand: a rare case for radiographic appearance, location, and
      age.
AB  - OBJECTIVE: This case describes the history, process of correct diagnosis, and
      treatment of a patient with pain in her left fourth finger, later found to be an
      osteosarcoma. CLINICAL FEATURES: A 28-year-old woman presented with pain in her
      left fourth finger, which she also noticed had been "getting bigger." Moderate
      tenderness and decreased range of motion were noticed over the
      metacarpophalangeal joint of the involved finger. INTERVENTION AND OUTCOME:
      Initial radiographs indicated a benign tumor with a pathological fracture, and
      the patient was referred to a hand surgeon. After debridement of the area, the
      pathology report returned with a diagnosis of osteoblastic osteogenic
      osteosarcoma. The patient then underwent amputation of the fourth ray and
      chemotherapy. CONCLUSION: This case presents a rare bone tumor of the hand and
      highlights the importance of clinical decision-making to lead to appropriate
      patient care.

PMID- 18328944
TI  - Gain at chromosomal region 5p15.33, containing TERT, is the most frequent genetic
      event in early stages of non-small cell lung cancer.
AB  - Chromosomal imbalances resulting in altered gene dosage play a role in the
      molecular pathogenesis of non-small cell lung cancer (NSCLC), but the target
      genes remain to be identified. To identify early-stage genetic events that drive
      progression of NSCLC, we conducted a high-resolution array comparative genomic
      hybridization (CGH) study, using an array of 4,046 bacterial artificial
      chromosome clones to screen for DNA copy number changes associated with
      individual genes in 36 tumors obtained from patients in early stages of NSCLC.
      Multiple early genetic events occurring on chromosome 5p were identified, with a
      minimal detection region at 5p15.33 approximately 12. The most frequent finding
      involved gain of 5p15.33, observed in 15 of 19 stage I (A+B) cancers (79%) and in
      28 of the total 36 NSCLC cases (78%). This locus harbors the genes TERT, SLC6A19,
      and SLC6A18 and is a telomeric boundary at bacterial artificial chromosome (BAC)
      clone 91_J20. Other potential candidate genes evidencing high numbers of genomic
      copy number changes (> or =40% of patients) included the following genes,
      encountered in >50% of 19 stage I (A+B) cancers: CEP72 and TPPP (14 of 19; 74%);
      AHRR, EXOC3 (previously SEC6L1), SLC9A3, LOC442126, ZDHHC11, BRD9, and TRIP13
      (13/19; 68%); and CLPTM1L (alias CRR9), SLC6A3 (previously DAT1), and LOC401169
      (10/19; 53%). Fluorescence in situ hybridization validated the array CGH
      findings. The gain of 5p15.33 is thus one of the most consistent alterations in
      the early stages of lung cancer, and a series of genes in the critical 5p15.33
      region may be used as novel biomarkers for the early detection and classification
      of lung cancer.

PMID- 18328945
TI  - Detection of human papillomavirus genotypes with liquid bead microarray in
      cervical lesions of northern Chinese patients.
AB  - Human papillomavirus (HPV) is the main cause of cervical cancer. Blending
      multiplex polymerase chain reaction (PCR) amplification and multiplex
      hybridization to liquid bead microarray (LBMA), we detected and identified 25
      common HPV genotypes using type-specific primers for HPV E6 and E7 genes in
      cervical lesions of northern Chinese patients. Of the 511 cervical samples, 349
      (68.3%) were found to be HPV positive by HPV-LBMA. The distribution was 22 HPV
      positive of 100 in the control group (22%), 41 of 80 with chronic cervicitis
      (51%), 80 of 99 with cervical intraepithelial neoplasia (CIN) I (81%), 46 of 56
      with CIN II (82%), 67 of 74 with CIN III (90%), and 93 of 102 with invasive
      cervical carcinoma (91%). HPV-16 was the most frequent genotype in the CIN and
      cervical cancer groups. The most common genotypes were HPV-16 (28%), HPV-58
      (14%), HPV-52 (14%), HPV-18 (8%), and HPV-33 (7%) in the CIN group, and HPV-16
      (63%), HPV-52 (9%), HPV-18 (7%), HPV-58 (7%), and HPV-33 (5%) in the cervical
      cancer group. HPV-LBMA found multiple genotypes in 1 of 22 control (4%), 64 of
      193 CIN (33%), and 22 of 93 cervical cancer (24%). The HPV-LBMA results were
      compatible with those of PCR and DNA sequencing. HPV-LBMA is a simple, high
      throughput method that provides useful information on viral genotype and multiple
      HPV infections in cervical lesions. In northern China, the most common high-risk
      HPV genotypes seem to be HPV types 16, 58, 52, 18, and 33. Genetic information on
      HPV in cervical specimens could provide particular benefits in the management of
      cervical lesions.

PMID- 18328946
TI  - Correlation between 6q25.3 deletion status and survival in pediatric intracranial
      ependymomas.
AB  - Losses and rearrangements of genetic material on chromosome 6q are frequently
      found in several human malignancies, including primary central nervous system
      tumors. We previously used microsatellite analysis of ependymomas to identify
      frequent deletions in regions 6q15 approximately q16, 6q21 approximately q22.1,
      and 6q24.3 approximately q25.3. To refine our preliminary analysis of potential
      prognostic regions, we used a panel of 25 microsatellite markers located between
      6q15 and 6qter in 49 pairs of matched normal and tumor specimens from 28 children
      and 21 adults with ependymoma. Allelic deletions were detected in 34 of 49
      patients (69%), and two common regions of deletions (6q24.3 and 6q25.2
      approximately q25.3) were identified. A short segment of approximately 0.4 Mb
      between D6S1612 and D6S363 on 6q25.3, containing the SNX9 and SYNJ2 genes,
      exhibited the highest number of aberrations (n = 38). Pediatric tumors showed
      slightly fewer aberrations (64%) than adult tumors (76%) and also predominantly
      exhibited small interstitial deletions, in contrast to the extensive losses of
      genetic material in adults. Pediatric anaplastic intracranial (supra- and
      infratentorial) ependymomas harboring the 6q25.3 deletion (n = 9) showed
      significantly longer overall survival than did patients of the same group without
      the aberration (n = 6), independent of the extent of resection (P = 0.013). This
      supports the identified deletion on 6q25.3 as a candidate favorable prognostic
      parameter and warrants further investigation.

PMID- 18328947
TI  - Coexistence of ETV6/RUNX1 and MLL aberrations in B-cell precursor acute
      lymphoblastic leukemia discloses a small subclass of BCP-ALL.
AB  - Out of 76 pediatric cases of B-cell precursor acute lymphoblastic leukemia (BCP
      ALL) positive for ETV6/RUNX1 (previously TEL/AML1) resulting from t(12;21), 7
      cases revealed coexistence of ETV6/RUNX1 and MLL aberrations. One case of der(21)
      duplication with ETV6/RUNX1 exhibited a novel MLL translocation variant
      t(6;11)(p21.1p23;q13q25), with translocation of 3' telomeric MLL and deletion of
      5' centromeric MLL. Another case of der(21) duplication with ETV6/RUNX1 showed
      MLL rearrangement upon Southern blotting. The remaining five ETV6/RUNX1-positive
      cases had MLL allelic deletion. ETV6/RUNX1 and MLL aberration clone size in these
      cases was suggestive of ETV6/RUNX1 as an early primary event, originating in the
      embryonic or infant stage and developing into leukemia by later acquisition of
      MLL aberration, ETV6 loss, and ETV6/RUNX1 duplication as secondary events. To
      date, the prognosis has been favorable, which seems to be compatible with
      ETV6/RUNX1-positive ALL. We conclude that the cases with coexisting ETV6/RUNX1
      and MLL aberrations probably exist as a small, hidden group of ETV6/RUNX1
      positive BCP-ALL, which invites further investigation, in large series from
      different populations, to confirm the findings and establish the biological
      mechanisms and prognostic significance.

PMID- 18328948
TI  - PPM1D silencing by RNA interference inhibits proliferation and induces apoptosis
      in breast cancer cell lines with wild-type p53.
AB  - PPM1D is an oncogene that is amplified and overexpressed in many human tumors,
      including breast cancer. It functions as a negative regulator of the p38 MAP
      kinase-p53 signaling pathway and is also proposed to participate in other
      critical cell survival pathways. To define the functional significance of PPM1D
      specifically in breast cancer, we used RNA interference to inhibit PPM1D
      expression in BT-474, MCF7, and ZR-75-1 breast cancer cell lines harboring
      amplification and increased expression of PPM1D. Efficient downregulation of
      PPM1D resulted in significantly reduced cell proliferation in MCF7 and ZR-75-1
      cells carrying wild-type p53 but not in BT-474 carrying mutant p53, which
      indicates that the antiproliferative effect of PPM1D silencing is dependent on
      the p53 status of the cells. This result is in excellent agreement with the
      notion that PPM1D activation is an alternative mechanism for p53 inactivation.
      Additionally, our data indicate that the reduced cell growth observed after PPM1D
      silencing is due at least in part to increased apoptotic cell death. Our findings
      demonstrate that PPM1D is involved in the regulation of cell proliferation in
      breast cancer in a p53-dependent manner and that overexpression of PPM1D
      contributes to malignant phenotype by promoting sustained cell growth and cell
      survival.

PMID- 18328949
TI  - Germline PTPN11 missense mutation in a case of Noonan syndrome associated with
      mediastinal and retroperitoneal neuroblastic tumors.
AB  - Noonan syndrome (NS) is an autosomal dominant disorder characterized by short
      stature, typical craniofacial dysmorphism, skeletal anomalies, congenital heart
      defects, and predisposition to malignant tumors. In approximately 50% of cases,
      the disease is caused by missense mutations in the PTPN11 gene. To date, solid
      tumors, and particularly brain tumors and rhabdomyosarcomas, have been documented
      in patients with NS; however, few cases of neuroblastoma associated with NS have
      been reported. Here we report an unusual case of neuroblastoma with mediastinal,
      retroperitoneal, and medullar locations associated in a NS patient carrying a
      PTPN11 germline missense mutation (p.G60A). This missense mutation occurs within
      the N-SH2 domain of the PTPN11 gene and has been reported to be associated with
      acute leukemia in NS patients. The association of this p.G60A PTPN11 mutation
      with neuroblastoma provides new evidence that gain of function PTPN11 mutations
      may play an important role in the pathogenesis of solid tumors associated with
      Noonan syndrome.

PMID- 18328950
TI  - Isolated myelosarcoma development in an adolescent chronic myeloid leukemia
      patient with t(9;22)(q34;q11.2), +8, +14, +21, and der(1)(p36).
AB  - Additional chromosomal abnormalities are found in 5-20% of patients during
      chronic phase of chronic myeloid leukemia and in 60-80% preceding or accompanying
      blast crisis. These abnormalities are important in disease progression and,
      because they may occur before hematological and clinical symptoms, can be taken
      as a prognostic indicator. An adolescent with chronic myeloid leukemia initially
      presented with extreme thrombocytosis, increased megakaryopoiesis with dysmorphic
      features, and focal myelofibrosis in bone marrow examinations and then developed
      isolated myelosarcoma 1 year after onset, with t(9;22)(q34;q11.2), +8, +14, +21,
      and der(1)(p36).

PMID- 18328951
TI  - A case of acute basophilic leukemia arising from chronic myelogenous leukemia
      with development of t(7;8)(q32;q13).
AB  - Acute basophilic leukemia (ABL) is an uncommon form of acute myelogenous leukemia
      recently recognized as a distinct entity in the World Health Organization
      classification of myeloid malignancies. A case is presented of ABL arising from
      chronic myelogenous leukemia with development of t(7;8)(q32;q13). Discussion
      includes a literature review.

PMID- 18328952
TI  - 5'RARA submicroscopic deletion from new variant translocation involving
      chromosomes 15, 17, and 18, in a case of acute promyelocytic leukemia.
AB  - Submicroscopic deletions of the PML-RARA fusion genes constitute rare
      rearrangements in acute promyelocytic leukemia (APL). We describe a rare case of
      APL carrying a novel complex translocation involving chromosomes 15, 17, and 18
      associated with a submicroscopic deletion of the 5' part of the RARA gene, as
      evidenced by fluorescence in situ hybridization (FISH). A PML/RARA dual-fusion
      probe did not reveal the RARA-PML fusion signal on the der(17q), usually detected
      in the typical t(15;17). The RARA break-apart probe showed a deletion
      hybridization pattern with loss of the signal corresponding to the 5' portion of
      the RARA gene. Reverse transcriptase-polymerase chain reaction confirmed the
      absence of the fusion RARA-PML transcript. The patient achieved complete
      remission, but died during consolidation therapy, 2 months after diagnosis. To
      our knowledge, this is the first reported case of APL with a complex variant
      t(15;17) involving chromosome 18 at band q12 and one of the very rare described
      cases displaying a submicroscopic deletion of the RARA 5' region. Further cases
      are needed to delineate the incidence of submicroscopic deletions in APL and
      elucidate their prognostic impact.

PMID- 18328953
TI  - Banding and molecular cytogenetic studies detected a CBFB-MYH11 fusion gene that
      appeared as abnormal chromosomes 1 and 16 in a baby with acute myeloid leukemia
      FAB M4-Eo.
AB  - The acute myeloid leukemia (AML) subtype M4Eo occurs in 5% of all AML cases and
      is usually associated with either an inv(16)(p13.1q22) or a t(16;16)(p13.1;q22)
      chromosomal abnormality. At the molecular level, these abnormalities generate a
      CBFB-MYH11 fusion gene. Patients with this genetic alteration are usually
      assigned to a low-risk group and thus receive standard chemotherapy. AML-M4Eo is
      rarely found in infants. We describe clinical, conventional banding, and
      molecular cytogenetic data for a 12-month-old baby with AML-M4Eo and a chimeric
      CBFB-MYH11 fusion gene masked by a novel rearrangement between chromosomes 1 and
      16. This rearrangement characterizes a new type of inv(16)(p13.1q22) masked by a
      chromosome translocation.

PMID- 18328954
TI  - Detection of gene amplification and copy gains in brain metastases of solid
      tumors using quantitative real-time polymerase chain reaction.

PMID- 18328955
TI  - Additional rearrangements affecting the derivative chromosome 9 involved in the
      standard Philadelphia translocation after imatinib therapy in a patient with
      chronic myeloid leukemia.

PMID- 18328956
TI  - Evaluation of an immunochemotherapeutic protocol constituted of N-methyl
      meglumine antimoniate (Glucantime) and the recombinant Leish-110f + MPL-SE
      vaccine to treat canine visceral leishmaniasis.
AB  - The evaluation of the efficacy of an immunochemotherapy protocol to treat
      symptomatic dogs naturally infected with Leishmania chagasi was studied. This
      clinical trial had the purpose to test the combination of N-methyl meglumine
      antimoniate (Glucantime and the second generation recombinant vaccine Leish-110f
      plus the adjuvant MPL-SE to treat the canine leishmaniasis (CanL). Thirty
      symptomatic naturally infected mongrel dogs were divided into five groups.
      Animals received standard treatment with Glucantime or treatment with Glucantime
      Leish-110f + MPL-SEas immunochemotherapy protocol. Additional groups received
      Leish-110f + MPL-SE only, MPL-SE only, or placebo. Evaluation of haematological,
      biochemical (renal and hepatic function) and plasmatic proteins, immunological
      (humoral and cellular immune response) and the parasitological test revealed
      improvement of the clinical parameters and parasitological cure in dogs in both
      chemotherapy alone and immunochemotherapy cohorts. However, the immunotherapy and
      immunochemotherapy cohorts had reduced number of deaths, higher survival
      probability, and specific cellular reactivity to leishmanial antigens, in
      comparison with chemotherapy cohort only and control groups (adjuvant alone and
      placebo). These results support the notion of using well-characterized
      recombinant vaccine as an adjunct to improve the current chemotherapy of CanL.

PMID- 18328957
TI  - New developments in analysis of turns and sequences in clinical communication
      research.

PMID- 18328958
TI  - Collateral damages.

PMID- 18328959
TI  - Demographic and illness-related variables associated with HIV-related fatigue.
AB  - Fatigue is one of the most debilitating symptoms suffered by those with HIV
      infection, yet little is known about its correlates. The primary aims of this
      study were to describe the degree to which fatigue affects daily functioning and
      the demographic and illness-related predictors of fatigue. The sample (n = 128)
      was composed of primarily poor, unemployed people of color. Fatigue most often
      interfered with the ability to think quickly, perform household chores, exercise,
      work, engage in recreational activities, walk, plan activities, and think
      clearly. The consequences of fatigue were highest for lowered motivation,
      difficulty concentrating, increased drowsiness, losing patience, and interference
      with work, family, and social life. Multiple linear regression analyses showed
      statistically significant associations of employment status, monthly income,
      current antidepressant use, and number of years living with HIV infection as
      predictors of fatigue. These must be better understood to develop interventions
      to successfully ameliorate HIV-related fatigue.

PMID- 18328961
TI  - Knowledge and attitudes of Ugandan midwives regarding HIV.
AB  - In Uganda, 60% of HIV-infected adults are women of childbearing age. Considering
      this, midwives in Uganda play a pivotal role in reducing HIV transmission and
      providing high quality care to the many women and families affected by the
      disease. In this pilot study, investigators described the knowledge and attitudes
      of Uganda's private midwives regarding HIV. Overall knowledge levels were
      reported to be low, and the majority of participants reported overwhelming fear
      of contracting the disease from practice. Despite these challenges, the midwives'
      attitudes regarding HIV were positive. The results of this study support previous
      results. Additional studies focusing on midwives and traditional birth attendants
      in Uganda are warranted. The initiation of HIV continuing education programs and
      professional support for Ugandan midwives is also recommended.

PMID- 18328960
TI  - Barriers and facilitators to medication adherence in a southern minority
      population with HIV disease.
AB  - Adherence to HIV medications has been an important focus over the past decade,
      but little is known about adherence barriers and facilitators specifically in
      that part of the United States known as the Deep South. Characteristics of the
      region may affect factors associated with adherence related to the patient, the
      patient-provider relationship, and the environment. A total of 20 HIV-infected
      clients of a large public infectious diseases clinic in the Deep South
      participated in one of three focus groups; themes were identified by content
      analysis. Barriers included the perceived burden of extra planning, denial, life
      stress, difficult characteristics of the medicines, social stigma, and shame.
      Facilitators included acceptance of the diagnosis, thinking about the
      consequences of not taking the medicines, prayer and spirituality, improvements
      in the medicines, and support from family and friends. In the South, faith and
      prayer may be strong facilitators that need to be considered when adapting
      existing adherence interventions.

PMID- 18328962
TI  - HIV-infected mothers' foci of concern during the viral testing of their infants.
AB  - The objective of this study was to explore HIV-infected mothers' most worrisome
      concerns during their infants' HIV viral testing. A total of 20 HIV-infected
      women consented to one antepartum and five postpartum study visits clustered
      around infant HIV viral testing time points. Content analysis was used to
      categorize maternal responses about their concerns. The majority (80%) of mothers
      identified infant health as the most worrisome concern during the prenatal and
      early postpartum periods. This concern declined after the second infant viral
      test result but rebounded before obtaining the final viral test. Once the final
      viral test result was known, the majority (60%) of mothers identified
      psychosocial issues as most worrisome. Maternal health did not surpass infant
      health or psychosocial issues as a primary concern. The primary concern of the
      HIV-infected mothers in this study was infant health during the infant viral
      testing period. Maternal health issues remained secondary to infant health and
      psychosocial issues as major concerns several months after infant viral testing
      was completed.

PMID- 18328963
TI  - Beliefs about HIV disease and medication adherence in persons living with
      HIV/AIDS in rural southeastern North Carolina.
AB  - The purpose of this study was to assess personal beliefs about the causes and
      meaning of having HIV disease and personal beliefs about medication adherence in
      persons living in rural southeastern North Carolina. Of the total sample of 34
      participants, 29 (85%) were African American. The sample included 21 men (62%)
      and 13 women (38%), with a self-reported mean CD4 count of 499.38 (SD = 377.69)
      and a mean duration of HIV of 8.0 years. The majority of participants held
      beliefs that HIV was a serious and chronic condition and that the disease could
      be controlled by HIV therapies. Participants offered disparate views about
      whether or not the course of HIV disease was amenable to personal control. The
      persons who held the belief that the cause of HIV/AIDS was because of chance/bad
      luck (p = .03) or God's will (p < .001) were also most likely to believe that the
      progression of their HIV disease depended on chance or fate. The respondents
      currently taking HIV medication were also more likely to believe that HIV was
      caused by chance or bad luck (p = .038) or God's will (p = .016). The results
      reflect the important role of spirituality on self- regulation of illness and
      treatment in the rural southern culture.

PMID- 18328964
TI  - Coping with HIV-related stigma in five African countries.
AB  - People living with HIV (PLWH) and their families are subjected to prejudice,
      discrimination, and hostility related to the stigmatization of AIDS. This report
      examines how PLWH cope with HIV-related stigma in the five southern African
      countries of Lesotho, Malawi, South Africa, Swaziland, and Tanzania. A
      descriptive qualitative research design was used to explore the experience of HIV
      related stigma of PLWH and nurses in 2004. A total of 43 focus groups were
      conducted with 251 participants (114 nurses, 111 PLWH, and 26 volunteers). In
      describing incidents of stigma, respondents reported strategies used or observed
      to cope with those incidents. Nurse reports of coping strategies that they used
      as well as observed in HIV-infected patients were coded. Coping strategies used
      by PLWH in dealing with HIV-related stigma were coded. A total of 17 different
      self-care strategies were identified: restructuring, seeing oneself as OK,
      letting go, turning to God, hoping, changing behavior, keeping oneself active,
      using humor, joining a support or social group, disclosing one's HIV status,
      speaking to others with same problem, getting counseling, helping others to cope
      with the illness, educating others, learning from others, acquiring knowledge and
      understanding about the disease, and getting help from others. Coping appears to
      be self-taught and only modestly helpful in managing perceived stigma.

PMID- 18328965
TI  - A developmental psychopathology framework of the psychosocial needs of children
      orphaned by HIV.
AB  - In addition to the obstacles to a successful resolution of grief normally faced
      by children whose parents have died, children orphaned by AIDS may face
      additional psychological and social challenges. However, limited attention has
      been paid to psychosocial and developmental needs of children orphaned by
      HIV/AIDS, particularly in resource-poor countries or regions. In this article the
      authors review the global literature on child bereavement and AIDS orphan care
      experiences in developing countries and present a developmental psychopathology
      model of the psychosocial issues facing AIDS orphans. The authors identify gaps
      in the literature and provide suggestions for future research on AIDS orphans in
      resource-poor countries and regions. They emphasize that future studies need to
      assess the status of behaviors and mental health of children orphaned by AIDS
      within a developmental framework, identify those individual and social factors
      associated with grief, and examine the long-term impact of quality of care,
      developmental maturation, and attachment with caregivers on the psychosocial well
      being of AIDS orphans.

PMID- 18328966
TI  - Virologic response using directly observed therapy in adolescents with HIV: an
      adherence tool.
AB  - Virologic response to highly active antiretroviral therapy (HAART) treatment of
      HIV infection depends on viral sensitivity to antiretrovirals and excellent
      medication adherence. Adolescents with vertically acquired HIV may require
      complicated regimens because of significant treatment experience and often have
      poor medication adherence. A retrospective chart review identified five
      adolescents with vertically acquired HIV and plasma HIV viral load rebound or
      nonresponse on a stable HAART regimen followed by a period of directly observed
      therapy (DOT) in a clinic or hospital setting with serial viral load
      measurements. Four subjects had a virologic response (mean decline, 1.15 log10)
      after DOT. A response to HAART can be seen despite antiretrovirals resistance
      using DOT and treatment-experienced patients seemingly unresponsive to HAART may
      be nonadherent even with reassuring adherence measures. A period of clinic
      monitored DOT may allow diagnosis of nonadherence, discussion of medication
      barriers, and avoidance of unnecessary medication changes.

PMID- 18328968
TI  - Above all, do no harm.

PMID- 18328969
TI  - Survey-based research: performing the survey.

PMID- 18328971
TI  - Outcomes of pediatric trauma patients transported from rural and urban scenes.
AB  - OBJECTIVES: Mortality differences exist between victims of urban and rural
      trauma. It is unknown if these differences persist in those patients who survive
      to HEMS transport. This study examined the in-hospital mortality, hospital LOS,
      and discharge status of pediatric blunt trauma victims transported by HEMS from
      rural and urban scenes. METHODS: Retrospective review of pediatric (< 17)
      transports between 1997 and 2001. 130 rural and 419 urban pediatric patients
      transported to area trauma centers were identified from HEMS and registry
      records. RESULTS: Total mileage, flight times, and scene times were significantly
      longer for rural flights (P < 0.05). There were no significant differences
      between the groups with regard to age, gender, vitals, hospital/ICU days, and
      mortality. After controlling for ISS and mechanism of injury, urban patients were
      9 times more likely to die compared to rural patients. CONCLUSIONS: Pediatric
      patients injured in urban areas had shorter total flight and scene times than
      pediatric patients flown from rural scenes. Higher adjusted in-hospital mortality
      rates in the urban group were likely a result of faster EMS response and
      transport times, which minimized out-of-hospital deaths. Factors prior to HEMS
      arrival may have more impact on the increased mortality rates of rural blunt
      trauma victims documented nationally.

PMID- 18328972
TI  - Formal testing and utilization of streaming media to improve flight crew safety
      knowledge.
AB  - Increased concerns over the safety of air medical transport have prompted
      development of novel ways to increase safety. The objective of our study was to
      determine if an Internet streaming media safety video increased crew safety
      knowledge. 23 out of 40 crew members took an online safety pre-test, watched a
      safety video specific to our program and completed immediate and long-term post
      testing 6 months later. Mean pre-test, post-test and 6 month follow up test
      scores were 84.9%, 92.3% and 88.4% respectively. There was a statistically
      significant difference in all scores (p <or= 0.01). Streaming media proved to be
      an accessible and effective supplement to safety training in our study.

PMID- 18328973
TI  - Evaluation of two oxygen face masks with special regard to inspiratory oxygen
      fraction (FiO2) for emergency use in rescue helicopters.
AB  - INTRODUCTION: Effective oxygenation during acute respiratory insufficiency
      depends on the inspiratory oxygen fraction (FiO(2)) and the oxygen face mask
      used. Recent studies demonstrated significant advantages of the Hi-Ox80 mask as
      compared with a basic mask. The aim of this study was to measure FiO(2) in the
      laryngopharynx of patients and to apply these data to the setting in rescue
      helicopters. METHODS: In spontaneously breathing patients, FiO(2) was measured
      with an O(2)-sensor (Draeger Medical, Luebeck, Germany) in the laryngopharynx,
      depending on the adjusted oxygen flow. Flow increments of 1 up to 12 L/min were
      analyzed using a basic oxygen mask (Intersurgical Ltd., Berkshire, UK) and a Hi
      Ox80 mask (Viasys Healthcare GmbH, Hoechberg, Germany) in a randomized order on
      the same patient. Data were applied to the special helicopter environment and
      analyzed with respect to oxygen delivery per minute and resulting equipment
      benefits. Statistika (StatSoft GmbH, Hamburg, Germany) and t-test were used for
      statistical analysis. P <or= .05 was considered statistically significant.
      RESULTS: Twenty patients with a mean age of 69 +/- 7 years were investigated. At
      a low oxygen flow up to 1 L/min, the Hi-Ox80 mask was not superior to the basic
      mask (FiO(2) at 1 L/min 24% +/- 3% vs. 27% +/- 5% and partial pressure of
      arterial oxygen [paO(2)] 164 +/- 68 vs. 193 +/- 53 mmHg; NS). Using a flow of 2
      L/min or more, a significant difference for the FiO(2) and paO(2) in both masks
      was found (P <or= .05). Using the Hi-Ox80 face mask in a rescue helicopter with
      standard oxygen flows, it demonstrated 3.24 times longer oxygen availability
      because of a reduced required oxygen flow and therefore a potential calculated
      weight reduction. CONCLUSIONS: The Hi-Ox80 mask allows more effective use of the
      administered oxygen flow. Efficiency of the new mask is greater; hence, similar
      flow adjustment produces a significantly higher FiO(2). Thus, oxygen, cost, and
      weight savings are feasible.

PMID- 18328974
TI  - Air medical evacuation in patients with airleak syndromes.

PMID- 18328975
TI  - Cold but not dead.

PMID- 18328976
TI  - Orphan musculoskeletal and metabolic bone diseases.

PMID- 18328977
TI  - Achondroplasia.
AB  - Achondroplasia (MIM 100800) is the most common non-lethal skeletal dysplasia. Its
      incidence is between one in 10,000 and one in 30,000. The phenotype is
      characterized by rhizomelic disproportionate short stature, enlarged head,
      midface hypoplasia, short hands and lordotic lumbar spine, associated with normal
      cognitive development. This autosomal-dominant disorder is caused by a gain-of
      function mutation in the gene encoding the type 3 receptor for fibroblast growth
      factor (FGFR3); in more than 95% of cases, the mutation is G380R. The diagnosis
      is suspected on physical examination and confirmed by different age-related
      radiological features. Anticipatory and management care by a multidisciplinary
      team will prevent and treat complications, including cervical cord compression,
      conductive hearing loss and thoracolumbar gibbosity. Weight counselling,
      psychosocial guidance and professional integration programmes play an important
      role in the global quality of life of these patients and their families.

PMID- 18328978
TI  - Multiple epiphyseal dysplasia: clinical and radiographic features, differential
      diagnosis and molecular basis.
AB  - Multiple epiphyseal dysplasia is one of the more common skeletal dysplasias but
      it can still be difficult to diagnose. The presenting signs are often
      rheumatological ('joint pain') or neurological ('myopathy') in nature, and the
      cardinal feature of skeletal dysplasia (short stature) may not be present. A
      radiographic skeletal survey is necessary to delineate the pattern of generalized
      delayed epiphyseal ossification and changes in epiphyseal contour. Once the
      diagnosis of multiple epiphyseal dysplasia has been established, careful
      examination of the radiographs can help to determine which genes should be
      analysed. Mutations in at least six different genes can cause multiple epiphyseal
      dysplasia, and it can be either dominant or recessive. Molecular diagnosis is
      important for accurate prognosis and genetic counselling.

PMID- 18328979
TI  - Spondylo-epi-metaphyseal dysplasia.
AB  - The spondylo-epi-metaphyseal dysplasias (SEMD) are a heterogeneous group of
      disorders comprising more than 20 distinct entities with differing modes of
      inheritance, all defined by the combination of vertebral, epiphyseal and
      metaphyseal abnormalities. The presenting symptom of SEMD patients is usually
      disproportionate short stature. The diagnosis is either based on the specificity
      of the skeletal manifestations or on the presence of characteristic extraskeletal
      features which may appear during the course of the disease, highlighting the
      importance of follow-up of SEMD patients. The complications are variable but
      epiphyseal dysplasia is often a predominant feature, and the course of the
      disease is marked by premature osteoarthritis. A systematic survey of odontoid
      hypoplasia responsible for atlantoaxial instability with a risk of spinal cord is
      also required.

PMID- 18328980
TI  - Hereditary multiple exostoses and enchondromatosis.
AB  - Hereditary multiple exostoses (HME) is an autosomal-dominant disorder
      characterized by the development of benign tumours, multiple osteochondromas
      (exostoses), growing outward from the metaphyses of long bones. Birth prevalence
      is estimated to be one in 50,000, and the severity of the disease is variable.
      Osteochondromas may cause complications including pain, deformities and
      shortening of the long bones, restricted motion of joints, nerve or blood vessel
      compression, and malignant transformation (5% of cases) in adulthood. HME is a
      genetically heterogeneous disorder and is associated with mutations in EXT1 or
      EXT2 genes, which are both tumour suppressor genes. EXT genes encode
      glycosyltransferases, termed 'exostosins', which are involved in the biosynthesis
      of heparan sulphate. Enchondromatosis (or Ollier disease) is characterized by the
      presence of intra-osseous benign cartilaginous tumours. The estimated prevalence
      of the disease is one in 100,000. An asymmetrical distribution of cartilage
      lesions is observed in the disease. The number, size and location of the
      enchondromas can be extremely variable between patients. Clinical problems caused
      by enchondromas include skeletal deformities, limb length discrepancy, pain and
      the potential risk for malignant change to chondrosarcoma (20-50% of cases). The
      condition in which multiple enchondromas is associated with haemangiomas is known
      as 'Maffucci syndrome'. Ollier disease and Maffucci syndrome are not usually
      inherited disorders.

PMID- 18328981
TI  - Fibrous dysplasia of bone and McCune-Albright syndrome.
AB  - Fibrous dysplasia of bone is a genetic, non-inheritable disease, characterized by
      bone pain, bone deformities and fracture, involving one or several bones. It is
      caused by mis-sense mutations occurring post-zygotically in the gene coding for
      the alpha-subunit of the stimulatory G-protein, Gs, in the guanine nucleotide
      binding, alpha stimulating (GNAS) complex locus in chromosome 20q13. This
      mutation results in osteoblastic differentiation defects, and bone resorption is
      often increased. The bone lesions may be associated with endocrine dysfunctions
      and cafe-au-lait spots; this is known as McCune-Albright syndrome. Patients with
      polyostotic fibrous dysplasia often have renal phosphate wasting. The disease,
      however, has a wide clinical spectrum, so many patients are asymptomatic.
      Diagnosis relies on radiographs and pathology. Bisphosphonates have been used in
      the treatment of fibrous dysplasia to relieve bone pain and improve lytic
      lesions, but they are still under clinical evaluation. Calcium, vitamin D and
      phosphorus supplements may be useful in some patients. Surgery is also helpful to
      prevent and treat fracture and deformities.

PMID- 18328982
TI  - Sclerosing bone disorders.
AB  - Sclerosing bone disorders are a diagnostic challenge. However, hereditary
      sclerosing disorders often have characteristic radiological features that allow
      their diagnosis. Osteocondensation can result from decreased bone resorption;
      malignant recessive osteopetroses have been related to mutations in several genes
      necessary for osteoclast function and also, more recently, to osteoclast
      differentiation (RANK-L). Albers-Schonberg disease or autosomal-dominant
      osteopetrosis type II has the characteristic 'sandwich vertebrae' and 'bone
      within bone' radiological features. It has been related to mutation in chloride
      channel 7, which is necessary for osteoclast acidification. Osteocondensation can
      also be related to increased bone formation. Camurati-Engelman dysplasia is a
      disabilitating disorder with leg pain and weakness, and thickening of the
      diaphysis of long bones on x ray. It is due to activating mutations in the gene
      encoding TGF-beta, a growth factor that increases bone formation. Other less
      common recessive or dominant sclerosing disorders, such as endosteal
      hyperostosis, sclerostosis, van Buchen disease and high bone mass syndrome, are
      due to mutations in two genes (LRP5 and SOST) of the Wnt pathway that induce
      increased osteoblast activity. Recent elucidation of the molecular mechanism
      responsible for several hereditary diseases with osteocondensation has improved
      our comprehension of bone remodelling. It has allowed the discovery of new
      targets for the treatment of postmenopausal osteoporosis, some of which are
      already being investigated in clinical trials. Molecular mechanism for some
      hereditary osteocondensation remains to be discovered.

PMID- 18328983
TI  - Osteogenesis imperfecta.
AB  - Osteogenesis Imperfecta is a heritable disorder characterized by bone fragility
      and low bone mass, with a wide spectrum of clinical expression. This review gives
      an update on its classification, the recent developments in the understanding of
      its pathophysiological mechanisms, and the current status of bisphosphonate
      therapy. Other therapeutic approaches and future directions of research are
      briefly discussed.

PMID- 18328984
TI  - Juvenile Paget's disease, familial expansile osteolysis and other genetic
      osteolytic disorders.
AB  - Several rare inherited osteolytic disorders have been described that show
      phenotypic overlap with Paget's disease of bone (PDB). Familial expansile
      osteolysis, early-onset familial PDB and expansile skeletal hyperphosphatasia are
      related disorders caused by mutations affecting the TNFRSF11A gene, which encodes
      the receptor activator of NFkappaB (RANK). The mutations result in failure of
      normal processing of RANK and osteoclast activation. Inactivating mutations in
      the TNFRSF11B gene, which encodes osteoprotegerin, cause idiopathic
      hyperphosphatasia which is a severe disorder that shares phenotypic similarities
      with PDB. The syndrome of hereditary inclusion body myopathy, PDB and
      frontotemporal dementia is caused by mutations in the gene encoding for valosin
      containing protein which is involved in regulating degradation of ubiquitinated
      proteins. Anecdotal reports indicate that osteoclast inhibitors such as
      bisphosphonates are effective for suppressing bone turnover and improving
      symptoms in these disorders, although the long-term effects on clinical outcomes
      are unclear.

PMID- 18328985
TI  - Hypophosphatasia.
AB  - Hypophosphatasia is a rare inherited disorder characterized by defective bone and
      tooth mineralization, and deficiency of serum and bone alkaline phosphatase
      activity. The frequency of the disease has been estimated to be one in 100 000
      for severe forms, but mild forms of hypophosphatasia may be more common. The
      symptoms are highly variable in their clinical expression, which ranges from
      stillbirth without mineralized bone to early tooth loss without bone symptoms.
      The transmission of severe forms is autosomal recessive, while milder forms may
      be transmitted as dominant or recessive autosomal traits. The diagnosis is based
      on serum alkaline phosphatase assay and molecular analysis of the
      liver/bone/kidney alkaline phosphatase gene (ALPL). Currently, there is no
      treatment for the disease. Over the past 10 years, great progress has been made
      in understanding the structure of tissue non-specific alkaline phosphatase, its
      function in bone mineralization, and the effect of ALPL mutations responsible for
      hypophosphatasia.

PMID- 18328986
TI  - Hypercalcaemic and hypocalcaemic conditions due to calcium-sensing receptor
      mutations.
AB  - The extracellular calcium (Ca2+o)-sensing receptor (CaSR) enables the parathyroid
      glands and other CaSR-expressing cells involved in calcium homeostasis, such as
      the kidney and bone, to sense alterations in the level of Ca2+o and to respond
      with changes in function that are directed at normalizing the blood calcium
      concentration. Several disorders of Ca2+o sensing arise from inherited or
      acquired abnormalities that 'reset' the serum calcium concentration upwards or
      downwards. Heterozygous inactivating mutations of the CaSR produce a benign form
      of hypercalcaemia, termed 'familial hypocalciuric hypercalcaemia', while
      homozygous mutations produce a much more severe hypercalcaemic disorder resulting
      from marked hyperparathyroidism, called 'neonatal severe hyperparathyroidism'.
      Activating mutations cause a hypocalcaemic syndrome of varying severity, termed
      'autosomal-dominant hypocalcaemia or hypoparathyroidism' as well as Bartter's
      syndrome type V. Calcimimetic CaSR activators and calcilytic CaSR antagonists
      have also been developed with potential for use in the treatment of these
      disorders.

PMID- 18328987
TI  - Multiple endocrine neoplasms.
AB  - Multiple endocrine neoplasia type 1 (MEN1) and type 2 (MEN2) are rare autosomal
      dominant disorders characterized by primary tumours in at least two different
      endocrine tissues. Both syndromes present as sporadic (a single case with two of
      the characteristic endocrine tumours) or familial form (an MEN case plus at least
      one first-degree relative showing one of the characteristic endocrine tumours).
      MEN1 is characterized by the occurrence of parathyroid, gastro-entero-pancreatic
      and anterior pituitary tumours, but it can include various combinations of more
      than 20 endocrine and non-endocrine tumours. Generally, tumours in MEN1 are
      benign, although gastrinomas and foregut carcinoids may exhibit a malignant
      course. MEN2 is characterized by medullary thyroid carcinoma (MTC), uni- or bi
      lateral pheochromocytoma, and other tumours of different endocrine tissues. If
      not diagnosed precociously, MTC can be fatal. MEN1 develops after tissue
      inactivation of both MEN1 gene copies. Activating mutations of c-RET proto
      oncogene causes MEN2.

PMID- 18328988
TI  - Ehlers-Danlos syndromes and Marfan syndrome.
AB  - Ehlers-Danlos syndromes (EDS) and Marfan syndrome (MFS) are multisystemic
      disorders that primarily affect the soft connective tissues. Both disorders have
      benefited from recent advances in clinical and molecular characterization,
      allowing improvements in clinical diagnosis and management. EDS are a
      heterogeneous group of conditions characterized by skin hyperextensibility,
      atrophic scarring, joint hypermobility and generalized tissue fragility. The
      current classification proposes six subtypes based on clinical, biochemical and
      molecular characteristics. However, examples of unclassified variants and
      'overlap phenotypes' are becoming more common. Mutations in genes encoding
      fibrillar collagens or collagen-modifying enzymes have been identified in most
      forms of EDS, including the classic and vascular subtypes (collagen type V and
      III, respectively), and the rare arthrochalasis, kyphoscoliosis and
      dermatosparaxis variants (type I collagen defects). To date, the genetic
      background of the hypermobility type of EDS remains unclear, although some new
      insights have been gained recently. MFS is an autosomal-dominant disorder that
      affects the cardiovascular, ocular and skeletal system with aortic root
      dilation/dissection, ectopia lentis and bone overgrowth, respectively. Advances
      in therapeutic, mainly surgical, techniques have improved median survival
      significantly, yet severe morbidity and a substantial risk for premature
      mortality remain associated. The disorder is caused by mutations in the FBN1
      gene, encoding the microfibrillar protein fibrillin-1. Recently, new insights in
      the pathogenesis changed the prevailing concept of this type 1 fibrillinopathy as
      a structural disorder of the connective tissue into a developmental abnormality
      manifesting perturbed cytokine signalling. These findings have opened new and
      unexpected targets for aetiologically directed drug treatments.

PMID- 18328989
TI  - Fibrodysplasia ossificans progressiva.
AB  - Fibrodysplasia ossificans progressiva (FOP), a rare and disabling genetic
      condition of congenital skeletal malformations and progressive heterotopic
      ossification (HO), is the most catastrophic disorder of HO in humans. Episodic
      disease flare-ups are precipitated by soft tissue injury, and immobility is
      cumulative. Recently, a recurrent mutation in activin receptor IA/activin-like
      kinase 2 (ACVR1/ALK2), a bone morphogenetic protein (BMP) type I receptor, was
      reported in all sporadic and familial cases of classic FOP, making this one of
      the most highly specific disease-causing mutations in the human genome. The
      discovery of the FOP gene establishes a critical milestone in understanding FOP,
      reveals a highly conserved target for drug development in the transforming growth
      factor (TGF)-beta/BMP signalling pathway, and compels therapeutic approaches for
      the development of small molecule signal transduction inhibitors for ACVR1/ALK2.
      Present management involves early diagnosis, assiduous avoidance of iatrogenic
      harm, and symptomatic amelioration of painful flare-ups. Effective therapies for
      FOP, and possibly for other common conditions of HO, may potentially be based on
      future interventions that block ACVR1/ALK2 signalling.

PMID- 18328990
TI  - Adolescent suicide: risk factors and prevention strategies. Foreword.

PMID- 18328991
TI  - Adolescent suicide: risk factors and prevention strategies.

PMID- 18328993
TI  - Audiovisual tau effect.
AB  - This study investigated how spatial intervals between successive visual flashes
      are influenced by the temporal intervals between auditory pure tones presented
      concurrently with the flashes. Three successive visual flashes defined two
      spatial intervals with different extents as well as two equal temporal intervals.
      The onsets of the first and third tones were temporally aligned with those of the
      first and third flashes, while the onset of the second tone was temporally offset
      to that of the second visual flash, resulting in shorter or longer temporal
      intervals between pairs of tones. Observers judged which of the first or second
      spatial intervals between flashes was shorter. The results showed that the
      shorter temporal interval between tones caused underestimation of the spatial
      interval between flashes. On the other hand, stimuli without the first and third
      tones did not result in underestimation of spatial intervals between flashes.
      These results indicate an audiovisual tau effect, which is triggered by a
      constant velocity assumption applied to moving objects defined by more than one
      modality.

PMID- 18328994
TI  - The Conference on Membrane electrochemistry. Foreword.

PMID- 18328995
TI  - Theoretical analysis of physicochemical processes occurring during water
      treatment by ozone and ultraviolet radiation.
AB  - The paper presents a kinetic model developed for ozone dissolution in water and
      taking into account convective and diffusion processes occurring in the vicinity
      of floating bubbles that contain an ozone-air mixture. It was shown that the
      gradient of ozone concentration in a convective-diffusion layer and consequently
      the rate of ozone transfer from bubbles to the solution depended on the rate of
      ozone decomposition both in its reaction with organic admixtures and in the
      conditions of exposure to ultraviolet radiation. The obtained kinetic curves of
      destruction of organic compounds and changes of ozone concentration in water and
      ozone-air mixture are compared with experimental data for humic acids. The paper
      also analyzes additional factors affecting the kinetics of ozone dissolution and
      the rate of resultant reactions.

PMID- 18328996
TI  - Outcomes of femtosecond laser-assisted penetrating keratoplasty.
AB  - PURPOSE: To evaluate outcomes from the use of a femtosecond laser to trephine
      both donor and recipient corneas during penetrating keratoplasty (PK). DESIGN:
      Prospective interventional case series. METHODS: Patients were recruited from the
      cornea clinic of the Singapore National Eye Centre. We used a 10-kHz Femtec
      (20/10 Perfect Vision, Heidelberg, Germany) femtosecond laser to perform
      trephination of the donor cornea on an artificial anterior chamber, followed by
      trephination of the recipient cornea. Trephination cuts were straight and
      performed 90 degrees to the corneal surface. Tissue bridges were bluntly
      separated with a Barrett phaco chopper. The donor button was then sutured to the
      recipient with double continuous sutures, or interrupted sutures if significant
      host corneal vascularization was present. Postoperatively, visual acuity,
      refraction, intraocular pressures, and optical coherence tomography (Visante;
      Carl Zeiss, Jena, Germany) were evaluated. RESULTS: Eight eyes of eight patients
      underwent PK for conditions ranging from bullous keratopathy to corneal scarring
      from herpetic stromal keratitis. Patients were followed up for a mean of 9.5
      months. Best-corrected visual acuities of patients with no ocular comorbidity
      ranged from 20/20 to 20/80. Mean cylindrical refractive error at last review was
      2.56 diopters [D] (range, 0.50 to 4.00 D). Tissue bridges were bluntly dissected
      except for one case that required scissors completion of trephination. No
      complications were encountered related to use of the Femtec laser. CONCLUSION:
      The Femtec laser reliably trephines both donor and recipient corneas for PK, with
      good visual outcomes and relatively low degrees of astigmatism.

PMID- 18328997
TI  - Correlations among upper and lower tear menisci, noninvasive tear break-up time,
      and the Schirmer test.
AB  - PURPOSE: To determine the relationships among tear meniscus parameters,
      noninvasive tear break-up time (NITBUT), and the Schirmer test. DESIGN:
      Experimental study. METHODS: Thirty-six subjects were tested on one randomly
      selected eye. Real-time corneal optical coherence tomography (OCT) was used to
      image the upper and lower tear menisci during normal and delayed blinking
      followed by measurement of NITBUT and the Schirmer test. Digital images of the
      eye were taken for measuring the lid lengths to estimate tear volume in the
      menisci. RESULTS: Compared with normal blinking, significant increases of tear
      menisci occurred during delayed blinking (post hoc, P < .01). NITBUT was weakly
      but significantly correlated with the height (r = 0.36; P = .03) and area (r =
      0.37; P = .03) of the lower tear meniscus during normal blinks. NITBUT was also
      correlated with the lower tear meniscus volume (r = 0.45; P < .05) and total tear
      meniscus volume (r = 0.43; P < .05) during normal blinking. The Schirmer test was
      not significantly related to any parameters of the tear menisci, volumes, or
      NITBUT; however, it was negatively correlated with the age of the subjects (r = 
      0.47; P = .004). The age was negatively correlated with the upper tear meniscus
      (r ranged from 0.36 to 0.37 for the radius, height, and area, P < .05) measured
      during delayed blinking. CONCLUSIONS: NITBUT appears correlated with the lower
      tear meniscus during normal blinking, and the Schirmer test appears not
      correlated with the noninvasively measured tear meniscus.

PMID- 18328998
TI  - Validation of the Ectasia Risk Score System for preoperative laser in situ
      keratomileusis screening.
AB  - PURPOSE: To validate the Ectasia Risk Score System for identifying patients at
      high risk for developing ectasia after laser in situ keratomileusis (LASIK).
      DESIGN: Retrospective case-control study. METHODS: Fifty eyes that developed
      ectasia and 50 control eyes with normal postoperative courses after LASIK were
      analyzed and compared using the previously described Ectasia Risk Score System,
      which assigns points in a weighted fashion to the following variables:
      topographic pattern, predicted residual stromal bed (RSB) thickness, age,
      preoperative corneal thickness (CT), and manifest refraction spherical equivalent
      (MRSE). RESULTS: In this series, 46 (92%) eyes with ectasia were correctly
      classified as being at high risk for the development of ectasia, while three (6%)
      controls were incorrectly classified as being at high risk for ectasia (P < 1 x
      10(-10)). Significantly more eyes were classified as high risk by the ectasia
      risk score than by traditional screening parameters relying on abnormal
      topography or RSB thickness less than 250 micro (92% vs 50%; P < .00001). There
      was no difference in the sensitivity or specificity of the Ectasia Risk Score
      System in the population from which it was derived and this independent
      population of ectasia cases and controls. CONCLUSIONS: The Ectasia Risk Score
      System is a valid and effective method for detecting eyes at risk for ectasia
      after LASIK and represents a significant improvement over previously utilized
      screening strategies.

PMID- 18328999
TI  - Corneal hysteresis and axial length among Chinese secondary school children: the
      Xichang Pediatric Refractive Error Study (X-PRES) report no. 4.
AB  - PURPOSE: To evaluate the association between corneal hysteresis and axial
      length/refractive error among rural Chinese secondary school children. DESIGN:
      Cross-sectional cohort study. METHODS: Refractive error (cycloplegic auto
      refraction with subjective refinement), central corneal thickness (CCT) and axial
      length (ultrasonic measurement), intraocular pressure (IOP), and corneal
      hysteresis (Reichert Ocular Response Analyzer) were measured on a rural school
      based cohort of children. RESULTS: Among 1,233 examined children, the mean age
      was 14.7 +/- 0.8 years and 699 (56.7%) were girls. The mean spherical equivalent
      (n = 1,232) was -2.2 +/- 1.6 diopters (D), axial length (n = 643) was 23.7 +/-
      1.1 mm, corneal hysteresis (n = 1,153) was 10.7 +/- 1.6 mm Hg, IOP (n = 1,153)
      was 17.0 +/- 3.4 mm Hg, and CCT (n = 1,226) was 553 +/- 33 microns. In linear
      regression models, longer axial length was significantly (P < .001 for both)
      associated with lower corneal hysteresis and higher IOP. Hysteresis in this
      population was significantly (P < .001) lower than has previously been reported
      for normal White children (n = 42, 12.3 +/- 1.3 mm Hg), when adjusting for age
      and gender. This difference did not appear to depend on differences in axial
      length between the populations, as it persists when only Chinese children with
      normal uncorrected vision are included. CONCLUSIONS: Prospective studies will be
      needed to determine if low hysteresis places eyes at risk for axial elongation
      secondary or if primary elongation results in lower hysteresis.

PMID- 18329000
TI  - A value-based medicine cost-utility analysis of idiopathic epiretinal membrane
      surgery.
AB  - PURPOSE: To perform a reference case, cost-utility analysis of epiretinal
      membrane (ERM) surgery using current literature on outcomes and complications.
      DESIGN: Computer-based, value-based medicine analysis. METHODS: Decision analyses
      were performed under two scenarios: ERM surgery in better-seeing eye and ERM
      surgery in worse-seeing eye. The models applied long-term published data
      primarily from the Blue Mountains Eye Study and the Beaver Dam Eye Study. Visual
      acuity and major complications were derived from 25-gauge pars plana vitrectomy
      studies. Patient-based, time trade-off utility values, Markov modeling,
      sensitivity analysis, and net present value adjustments were used in the design
      and calculation of results. Main outcome measures included the number of
      discounted quality-adjusted-life-years (QALYs) gained and dollars spent per QALY
      gained. RESULTS: ERM surgery in the better-seeing eye compared with observation
      resulted in a mean gain of 0.755 discounted QALYs (3% annual rate) per patient
      treated. This model resulted in $4,680 per QALY for this procedure. When
      sensitivity analysis was performed, utility values varied from $6,245 to
      $3,746/QALY gained, medical costs varied from $3,510 to $5,850/QALY gained, and
      ERM recurrence rate increased to $5,524/QALY. ERM surgery in the worse-seeing eye
      compared with observation resulted in a mean gain of 0.27 discounted QALYs per
      patient treated. The $/QALY was $16,146 with a range of $20,183 to $12,110 based
      on sensitivity analyses. Utility values ranged from $21,520 to $12,916/QALY and
      ERM recurrence rate increased to $16,846/QALY based on sensitivity analysis.
      CONCLUSIONS: ERM surgery is a very cost-effective procedure when compared with
      other interventions across medical subspecialties.

PMID- 18329001
TI  - Cholinergic submandibular effects and muscarinic receptor expression in blood
      vessels of the rat.
AB  - In order to functionally characterise the muscarinic vasodilator responses,
      effects of cholinergic agonists were studied on isolated preparations of the rat
      submandibular artery and vein and carotid and jugular vessels. Tentatively, a
      cholinergic regulatory mechanism having different effects on the arterial and
      venous vessels would enhance vascular fluid recruitment for the secretory
      response. In vitro functional findings were correlated to the expression and
      cellular location of the different receptors that were assessed by
      immunohistochemistry. In order to find in vivo correlates to the in vitro
      findings, the influence of muscarinic receptors on permeability was studied on
      the vasculature of the submandibular gland in anaesthetised rats. Staining for
      muscarinic M1 receptors occurred in the endothelium, and muscarinic M5 receptors,
      and possibly M3 also, were detected in the arterial smooth muscle. In venous
      endothelium, muscarinic M1 and M4 receptors occurred. In the jugular smooth
      muscle layer, staining for M1, and possibly also for M3, appeared. Muscarinic
      agonists caused arteries to relax and veins to contract. The nitric oxide
      synthase inhibitor Nomega-nitro-L-arginine (L-NNA; 10(-4)M) markedly reduced the
      cholinergic-evoked relaxation of pre-contracted carotid arterial preparations. In
      the presence of 4-DAMP (10(-7)M), the relaxation to cholinergic agonists was
      inhibited. Pirenzepine (10(-5)M) did not only inhibit the relaxatory effects, but
      even reversed the effects, while it in the jugular vein abolished the cholinergic
      effects. The arterial nitric oxide-dependent response to muscarinic receptor
      stimulation consisted of two parts -- one sensitive to pirenzepine and 4-DAMP and
      the other to 4-DAMP only. Inhibition of the former part only, resulted in
      cholinergic arterial contraction. Also, the submandibular artery and vein
      responses to muscarinic receptor stimulation show a resemblance with those of the
      carotid and jugular vessels, i.e. a pronounced arterial relaxation and a
      contractile component in the venous response. In vivo examination of
      submandibular glandular vasculature by studying glandular permeability to Evans
      blue, confirmed the in vitro observations indicating muscarinic M1 receptors
      preserving perfusion pressure during the secretory process.

PMID- 18329002
TI  - Bakuchiol analogs inhibit monoamine transporters and regulate monoaminergic
      functions.
AB  - Monoamine transporters play key roles in controlling monoamine levels and
      modulating monoamine reuptake. The objective of the present study was to identify
      monoamine transporter inhibitors from herbal sources. We discovered that
      bakuchiol analogs isolated from Fructus Psoraleae inhibited monoamine transporter
      uptake to differing degrees. The bakuchiol analog, Delta3,2-hydroxybakuchiol was
      the most potent and efficacious reuptake blocker and was thus selected as the
      candidate target. Monoamine transporter inhibition by Delta3,2-hydroxybakuchiol
      was more selective for the dopamine transporter (DAT) (IC50=0.58+/-0.1 microM)
      and norepinephrine transporter (NET) (IC50=0.69+/-0.12 microM) than for the
      serotonin transporter (SERT) (IC50=312.02+/-56.69 microM). Delta3,2
      Hydroxybakuchiol exhibited greater potency (pEC50 for DAT and NET) than bupropion
      and exhibited similar efficacy (E(max) for DAT and/or NET) to bupropion and
      GBR12,935. Pharmacokinetically, Delta3,2-hydroxybakuchiol competitively inhibited
      DAT and NET with partial reversibility and occupied cocaine binding sites.
      Moreover, Delta3,2-hydroxybakuchiol counteracted 1-methyl-4-phenylpyridinium
      induced toxicity in cells expressing DAT with similar efficacy to GBR12,935. In
      vivo studies showed that Delta3,2-hydroxybakuchiol increased the activity of
      intact mice and improved the decreased activity of reserpinized mice. In the
      conditioned place preference test, preference scores in intact mice were
      unaffected by Delta3,2-hydroxybakuchiol treatment. Bakuchiol analogs, especially
      Delta3,2-hydroxybakuchiol, are monoamine transporter inhibitors involved in
      regulating dopaminergic and noradrenergic neurotransmission and may have
      represented potential pharmacotherapies for disorders such as Parkinson's
      disease, depression, and cocaine addiction.

PMID- 18329003
TI  - 3,3'-diindolylmethane reduces levels of HIF-1alpha and HIF-1 activity in hypoxic
      cultured human cancer cells.
AB  - 3,3'-diindolylmethane (DIM) is a chemopreventive and chemotherapeutic
      phytochemical derived from the metabolism of indoles found at high concentrations
      in cruciferous vegetables. We have previously shown that DIM exhibits anti
      angiogenic properties in cultured vascular endothelial cells and in Matrigel plug
      assays in rodents. In the present study, we demonstrate that DIM reduces the
      level of hypoxia-inducible factor (HIF)-1alpha in hypoxic tumor cell lines, as
      well as HIF-1 transcriptional activity as measured by a reporter assay. Moreover,
      DIM inhibited the expression of HIF-1-responsive endogenous genes, resulting in
      the reduced expression of key hypoxia responsive factors, VEGF, furin, enolase-1,
      glucose transporter-1 and phosphofructokinase. DIM reduced the level of HIF
      1alpha in hypoxic cells by increasing the rate of the prolylhydroxylase- and
      proteasome-mediated degradation of HIF-1alpha, and by decreasing the rate of HIF
      1alpha transcription. Using enzyme kinetics studies, we established that DIM
      interacts with the oligomycin-binding site on the F0 transmembrane component of
      mitochondrial F1F0-ATPase. The contributions of the resulting increases in levels
      of ROS and O2 in hypoxic cells to the inhibitory effects of DIM on HIF-1alpha
      expression are discussed. These studies are the first to show that DIM can
      decrease the accumulation and activity of the key angiogenesis regulatory factor,
      HIF-1alpha, in hypoxic tumor cells.

PMID- 18329004
TI  - Metabolism of 17alpha-hydroxyprogesterone caproate by hepatic and placental
      microsomes of human and baboons.
AB  - Recent data from our laboratory revealed the formation of an unknown metabolite
      of 17 hydroxyprogesterone caproate (17-HPC), used for treatment of preterm
      deliveries, during its perfusion across the dually perfused human placental
      lobule. Previously, we demonstrated that the drug is not hydrolyzed, neither in
      vivo nor in vitro, to progesterone and caproate. Therefore, the hypothesis for
      this investigation is that 17-HPC is actively metabolized by human and baboon
      (Papio cynocephalus) hepatic and placental microsomes. Baboon hepatic and
      placental microsomes were investigated to validate the nonhuman primate as an
      animal model for drug use during pregnancy. Data presented here indicate that
      human and baboon hepatic microsomes formed several mono-, di-, and tri
      hydroxylated derivatives of 17-HPC. However, microsomes of human and baboon
      placentas metabolized 17-HPC to its mono-hydroxylated derivatives only in
      quantities that were a fraction of those formed by their respective livers,
      except for two metabolites (M16' and M17') that are unique for placenta and
      contributed to 25% and 75% of the total metabolites formed by human and baboon,
      respectively. The amounts of metabolites formed, relative to each other, by human
      and baboon microsomes were different suggesting that the affinity of 17-HPC to
      CYP enzymes and their activity could be species-dependent.

PMID- 18329005
TI  - Structure-activity relationship for adenosine kinase from Mycobacterium
      tuberculosis II. Modifications to the ribofuranosyl moiety.
AB  - Adenosine kinase (Ado kinase) from Mycobacterium tuberculosis is structurally and
      biochemically unique from other known Ado kinases. This purine salvage enzyme
      catalyzes the first step in the conversion of the adenosine analog, 2-methyl-Ado
      (methyl-Ado), into a metabolite with antitubercular activity. Methyl-Ado has
      provided proof of concept that the purine salvage pathway from M. tuberculosis
      may be utilized for the development of antitubercular compounds with novel
      mechanisms of action. In order to utilize this enzyme, it is necessary to
      understand the topography of the active site to rationally design compounds that
      are more potent and selective substrates for Ado kinase. A previous structure
      activity relationship identified modifications to the base moiety of adenosine
      (Ado) that result in substrate and inhibitor activity. In an extension of that
      work, 62 Ado analogs with modifications to the ribofuranosyl moiety,
      modifications to the base and ribofuranosyl moiety, or modifications to the
      glycosidic bond position have been analyzed as substrates and inhibitors of M.
      tuberculosis Ado kinase. A subset of these compounds was further analyzed in
      human Ado kinase for the sake of comparison. Although no modifications to the
      ribose moiety resulted in compounds as active as Ado, the best substrates
      identified were carbocyclic-Ado, 8-aza-carbocyclic-Ado, and 9-[alpha-l
      lyxofuranosyl]-adenine with 38%, 4.3%, and 3.8% of the activity of Ado,
      respectively. The most potent inhibitor identified, 5'-amino-5'-deoxy-Ado, had a
      K(i)=0.8muM and a competitive mode of inhibition. MIC studies demonstrated that
      poor substrates could still have potent antitubercular activity.

PMID- 18329006
TI  - Association analysis of methionine synthase gene 2756 A>G polymorphism and
      Alzheimer disease in a Chinese population.
AB  - Homocysteine has been identified to be associated with Alzheimer disease (AD) and
      methionine synthase (MS) is one of the enzymes involved in homocysteine
      metabolism. Confused data were reported on the association between the MS 2756
      A>G polymorphism and AD. To determine if this polymorphism could affect the
      occurrence of AD, we investigated the association between the MS 2756 A>G
      polymorphism and AD risk in 353 sporadic AD patients and 346 controls in a
      Chinese Han population. No significant differences of allele and genotype
      distributions between the AD cases and the controls were observed in the total
      samples, neither when the samples were stratified by age/age at onset and gender.
      When the samples were stratified by APOE epsilon4 status, a trend of A allele and
      AA genotype over-representation in the AD patients in comparison with the
      controls was observed, but it was not statistically significant (for the alleles,
      A versus G OR=1.549, 95% CI 0.920-2.609, p=0.098; for the genotypes, AA versus
      AG+GG OR=1.485, 95% CI 0.861-2.560, p=0.153). Similar trend was observed in the
      APOE epsilon4 non-carrier samples of the >or=65 year subgroups and it was not
      statistically significant too (for the alleles, A versus G OR=1.682, 95% CI 0.901
      3.140, p=0.099, for the genotypes, AA versus AG+GG OR=1.690, 95% CI 0.884-3.232,
      p=0.110). Our data did not reveal significant association between the MS 2756 A>G
      polymorphism and AD development. However, a weak effect of the A allele on
      developing AD could not be completely excluded.

PMID- 18329007
TI  - Methamphetamine alters blood brain barrier permeability via the modulation of
      tight junction expression: Implication for HIV-1 neuropathogenesis in the context
      of drug abuse.
AB  - The pathogenesis of human immunodeficiency virus (HIV) associated encephalopathy
      is attributed to infiltration of the central nervous system (CNS) by HIV-1
      infected mononuclear cells that transmigrate across the blood brain barrier
      (BBB). The endothelial tight junctions (TJ) of the blood brain barrier (BBB) play
      a critical role in controlling cellular traffic into the CNS. Neuropathogenesis
      of HIV-1 is exacerbated by drugs of abuse such as methamphetamine (Meth) which
      are capable of dysregulating BBB function. HIV-1 viral proteins like gp120 are
      both neurotoxic and cytotoxic and have been implicated in the development of HIV
      1 dementia (HAD). We hypothesize that gp120 in synergy with Meth can alter BBB
      permeability via the modulation of tight junction expression. We investigated the
      effect of Meth and/or gp120 on the basal expression of TJ proteins ZO-1, JAM-2,
      Occludin, Claudin-3 and Claudin-5, using in vitro cultures of the primary brain
      microvascular endothelial cells (BMVEC). Further, the functional effects of TJ
      modulation were assessed using an in vitro BBB model, that allowed measurement of
      BBB permeability using TEER measurements and transendothelial migration of
      immunocompetent cells. Our results show that both Meth and gp120 individually and
      in combination, modulated TJ expression, and these effects involved Rho-A
      activation. Further, both Meth and gp120 alone and in combination significantly
      decreased transendothelial resistance across the in vitro BBB and the enhanced
      transendothelial migration of immunocompetent cells across the BBB. An
      understanding of the mechanisms of BBB breakdown that lead to neurotoxicity is
      crucial to the development of therapeutic modalities for Meth abusing HAD
      patients.

PMID- 18329008
TI  - Lack of robust protective effect of quercetin in two types of 6-hydroxydopamine
      induced parkinsonian models in rats and dopaminergic cell cultures.
AB  - In the present study, we examined the ability of a flavonoid quercetin to prevent
      6-hydroxydopamine (6-OHDA)-induced oxygen radical formation and cytotoxicity in
      vitro and neurotoxicity in vivo. Quercetin (10-100 microM) had an acute
      significant antioxidant effect against the 6-OHDA-induced (30 microM) oxygen
      radical formation in catecholaminergic SH-SY5Y neuroblastoma cells. Moreover, in
      these cells, quercetin at 10-50 microM had a significant protective effect
      against 6-OHDA though at 100 microM it was itself harmful to the cells. The
      possible effect of quercetin in preventing neurotoxicity in unilateral medial
      forebrain bundle (full nigral lesion) or striatal (partial lesion) 6-OHDA rat
      lesion models of Parkinson's disease was studied in three treatment schedules: a
      7-day pre- or post-treatment or their combination. Rotational responses to
      apomorphine (0.1 mg/kg, subcutaneously) and d-amphetamine (2.5 mg/kg,
      intraperitoneally) were assessed at weeks 1 and 2 post-lesion. Quercetin had no
      consistent neuroprotective effect in either model at 50-200 mg/kg once a day or
      100 mg/kg twice a day. Furthermore, no protection was observed in tyrosine
      hydroxylase positive nigral cell numbers, striatal fiber density or in striatal
      levels of dopamine. These in vitro and in vivo results cast doubt on the theory
      that quercetin exerts reliable neuroprotective effects against 6-OHDA-induced
      toxicity. In vitro, quercetin seems to be protective at low doses but damaging at
      high doses.

PMID- 18329010
TI  - An improved algorithm for predicting free recalls.
AB  - Laming [Laming, D. (2006). Predicting free recalls. Journal of Experimental
      Psychology: Learning, Memory, and Cognition, 32, 1146-1163] has shown that, in a
      free-recall experiment in which the participants rehearsed out loud, entire
      sequences of recalls could be predicted, to a useful degree of precision, from
      the prior sequences of stimuli and rehearsals. This article describes an improved
      predictive algorithm, which is then used to re-analyse two further sets of free
      recall data. Prediction is compared, generically, with conventional modelling,
      represented here by three recent models of free recall that are concerned with
      recalls only, not with rehearsals. Some implications are drawn, from the use of
      rehearsal data by the predictive algorithm, for some of the constituent
      assumptions embodied in those three models.

PMID- 18329009
TI  - Neuroendocrine factors alter host defense by modulating immune function.
AB  - An increasing body of evidence demonstrates that there is bidirectional
      communication between the neuroendocrine and immune systems. Interaction between
      these systems results in a variety of outcomes, including the well documented
      "sickness behavior" elicited by cytokines of the immune system that can enter the
      brain and activate second messengers that modify neuronal activity. Crosstalk
      between the neuroendocrine and immune systems can also result in production of
      factors by the nervous and endocrine systems that alter immune cell function and
      subsequent modulation of immune responses against infectious agents and other
      pathogens. Continued exposure to molecules produced by the neuroendocrine system
      has also been known to increase susceptibility and/or severity of disease.
      Furthermore, neuroendocrine factors are thought to play a major role in gender
      specific differences in development of certain disorders, including
      autoimmune/inflammatory diseases that have a two to tenfold higher incidence in
      females compared to males. Neuroendocrine factors can affect immune cells at the
      level of gene transcription but have also been shown to modify immune cell
      activity by interacting with intracellular molecules, resulting in modified
      ability of these cells to mount a potent immune response. In this review, we will
      consider various effects of the neuroendocrine system and its proteins on
      specific populations of immune cells and associated responses in host immunity
      against pathogens. We will further discuss how this modification of immune cell
      activity by the neuroendocrine system can contribute to susceptibility/severity
      of disease development.

PMID- 18329011
TI  - Expression of the dominant negative retinoid receptor, RAR403, alters
      telencephalic progenitor proliferation, survival, and cell fate specification.
AB  - Retinoic acid (RA) signaling plays critical roles in diverse cellular processes
      during nervous system development. In mouse models, the roles for RA signals in
      telencephalic development remain unclear, partly because of the ambiguity of RA
      telencephalic sources after E8.75. Here, we have developed a genetic approach
      that utilizes Cre-lox technology to conditionally express a potent dominant
      negative retinoid receptor, RAR403, in vivo. This approach blocks RA signaling
      pathways at the receptor level, enabling the disruption of RA signals in contexts
      in which the RA source is unknown. RAR403 expression throughout the developing
      telencephalon causes pronounced hypoplasia resulting from defective proliferation
      in dorsal telencephalic progenitors and extensive cell death. Furthermore,
      Nkx2.1(+) progenitors in the medial ganglionic eminence (MGE) are misspecified
      such that they acquire a subset of lateral ganglionic eminence (LGE)-specific
      properties at the expense of MGE fates. This genetic approach reveals new roles
      for RA signaling in telencephalic proliferation, survival and fate specification,
      and underscores its utility in investigating the function of retinoid signaling
      pathways throughout peri- and postnatal development.

PMID- 18329012
TI  - Drosophila dLMO-PA isoform acts as an early activator of achaete/scute proneural
      expression.
AB  - The Drosophila bHLH proneural factors Achaete (Ac) and Scute (Sc) are expressed
      in clusters of cells (proneural clusters), providing the cells with the potential
      to develop a neural fate. Mediodorsal proneural patterning is mediated through
      the GATA transcription factor Pannier (Pnr) that activates ac/sc directly through
      binding to the dorsocentral (DC) enhancer of ac/sc. Besides, the Gfi
      transcription factor Senseless (Sens), a target of Ac/Sc, synergizes with ac/sc
      in the presumptive sensory organ precursors (SOPs). Here we investigate, through
      new genetic tools, the function of dLMO, the Drosophila LIM only transcription
      factor that was already known to control wing development. We show that dLMO gene
      encodes two isoforms, dLMO-RA and dLMO-RB. dLMO null and dLMO-RA(-) deletions
      have similar phenotypes, lacking thoracic and wing margin sensory organs (SO),
      while dLMO-RB(-) deletion has normal SOs. At early stages, dLMO-RA is expressed
      in proneural clusters, however later it is excluded from the SOPs. We found that
      dLMO functions as a Pnr coactivator to promote ac/sc expression. In the late
      SOPs, where dLMO-PA is not expressed, Pnr participates to the Sens-dependent
      regulation of ac/sc. Taken together these results suggest that dLMO-PA is the
      major isoform that is required for early activation of ac/sc expression.

PMID- 18329013
TI  - Effects of diesel exhaust inhalation on heart rate variability in human
      volunteers.
AB  - OBJECTIVES: Particulate matter (PM) air pollution is associated with alterations
      in cardiac conductance and sudden cardiac death in epidemiological studies.
      Traffic-related air pollutants, including diesel exhaust (DE) may be at least
      partly responsible for these effects. In this experimental study we assessed
      whether short-term exposure to DE would result in alterations in heart rate
      variability (HRV), a non-invasive measure of autonomic control of the heart.
      METHODS: In a double-blind, crossover, controlled-exposure study, 16 adult
      volunteers were exposed (at rest) in randomized order to filtered air (FA) and
      two levels of diluted DE (100 or 200 microg/m(3) of fine particulate matter) in 2
      h sessions. Before, and at four time points after each exposure we assessed HRV.
      HRV parameters assessed included both time domain statistics (standard deviation
      of N-N intervals (SDNN), and the square root of the mean of the sum of squared
      differences between successive N-N intervals (RMSSD)) and frequency domain
      statistics (high-frequency (HF) power, low-frequency (LF) power, and the LF/HF
      ratio). RESULTS: We observed an effect at 3-h after initiation of DE inhalation
      on the frequency domain statistics of HRV. DE at 200 microg/m(3) elicited an
      increase in HF power compared to FA (Delta=0.33; 95% CI: 0.01-0.7) and a decrease
      in LF/HF ratio (Delta=-0.74; 95% CI: -1.2 to -0.2). The effect of DE on HF power
      was not consistent among study participants. There was no DE effect on time
      domain statistics and no significant DE effect on HRV in later time points.
      CONCLUSIONS: We did not observe a consistent DE effect on the autonomic control
      of the heart in a controlled-exposure experiment in young participants. Efforts
      are warranted to understand discrepancies between epidemiological and
      experimental studies of air pollution's impact on HRV.

PMID- 18329014
TI  - Ezetimibe improves high fat and cholesterol diet-induced non-alcoholic fatty
      liver disease in mice.
AB  - Ezetimibe is a novel cholesterol and plant sterol absorption inhibitor that
      reduces plasma low-density lipoprotein-cholesterol by selectively binding to the
      intestinal cholesterol transporter, Niemann-Pick C1-Like 1. Mice deficient in
      Niemann-Pick C1-Like 1 are protected from high fat/cholesterol diet-induced fatty
      liver as well as hypercholesterolemia. The object of the present study was to
      determine whether ezetimibe treatment could reduce hepatic steatosis in diet
      induced obese mice. C57BL/6J mice were fed a high fat/cholesterol containing semi
      purified diet (45% Kcal fat and 0.12% cholesterol) for 7 months after weaning.
      These mice were not only obese, but also developed hepatomegaly and hepatic
      steatosis, with varying degrees of liver fibrosis and steatohepatitis. About 87%
      of the mice on the high fat/cholesterol diet for 7 months had elevated plasma
      alanine aminotransferase activity, a biomarker for non-alcoholic fatty liver
      disease. Chronic administration of ezetimibe for 4 weeks significantly reduced
      hepatomegaly by decreasing hepatic triglyceride, cholesteryl ester and free
      cholesterol in diet-induced obese mice fed high fat/cholesterol diet for 7
      months. Chronic ezetimibe treatment also significantly decreased plasma alanine
      aminotransferase activity. These results suggest that ezetimibe may be a novel
      treatment for high fat/cholesterol-induced non-alcoholic fatty liver disease.

PMID- 18329015
TI  - Aconitine induces prolonged seizure-like events in rat neocortical brain slices.
AB  - Aconitine effects on the hippocampal slice preparation have been well documented
      and include acute inhibitory and prolonged excitatory effects. To date, the
      effect of aconitine on neocortical activity has not been investigated. The aim of
      this study was to characterise the acute and long term effects of aconitine on
      cortical local field potential activity. Neocortical slices from juvenile Sprague
      Dawley rats were perfused at room temperature with aconitine in normal artificial
      cerebrospinal fluid (aCSF) (n=10). Spontaneous local field potential activity was
      recorded from the somatosensory cortex. The calcium dependence of aconitine
      induced activity was investigated using low-calcium aCSF (n=8). To isolate sodium
      and N-methyl-d-aspartate (NMDA) channel effects, phenytoin (n=4) and 2-amino-5
      phosphono-pentanoic acid (APV) (n=6) were co-administered with aconitine,
      respectively. Aconitine consistently induced a dramatic increase in population
      "spike" activity after prolonged (89.5+/-36.6 min) application in normal aCSF.
      This activity surge was eliminated in low-calcium aCSF and when aconitine was co
      administered with phenytoin and APV. The acute effects of aconitine application
      were variable and included an increase in the frequency of population spikes,
      appearance of oscillatory seizure-like activity and prolonged bursts of multiunit
      activity. No acute inhibitory effects were observed. Aconitine has acute and
      prolonged excitatory effects on neocortical activity. The latter is effected by
      calcium-dependent mechanisms, in keeping with known effects of aconitine on
      hippocampal slices. Both sodium and NMDA channels are involved in mediating the
      calcium-dependent aconitine effects.

PMID- 18329016
TI  - Non-random subcellular distribution of variant EKLF in erythroid cells.
AB  - EKLF protein plays a prominent role during erythroid development as a nuclear
      transcription factor. Not surprisingly, exogenous EKLF quickly localizes to the
      nucleus. However, using two different assays we have unexpectedly found that a
      substantial proportion of endogenous EKLF resides in the cytoplasm at steady
      state in all erythroid cells examined. While EKLF localization does not appear to
      change during either erythroid development or terminal differentiation, we find
      that the protein displays subtle yet distinct biochemical and functional
      differences depending on which subcellular compartment it is isolated from, with
      PEST sequences possibly playing a role in these differences. Localization is
      unaffected by inhibition of CRM1 activity and the two populations are not
      differentiated by stability. Heterokaryon assays demonstrate that EKLF is able to
      shuttle out of the nucleus although its nuclear re-entry is rapid. These studies
      suggest there is an unexplored role for EKLF in the cytoplasm that is separate
      from its well-characterized nuclear function.

PMID- 18329017
TI  - MARCKS is a downstream effector in platelet-derived growth factor-induced cell
      motility in activated human hepatic stellate cells.
AB  - Myristoylated alanine-rich protein kinase c substrate (MARCKS) has been suggested
      to be implicated in cell adhesion, secretion, motility and mitogenesis through
      regulation of the actin cytoskeletal structure. In the present study, a possible
      link between MARCKS and the platelet-derived growth factor (PDGF) signaling
      pathway was investigated in activated human hepatic stellate cells (hHSC),
      critical regulators of hepatic fibrogenesis. PDGF-BB stimulation resulted in a bi
      directional movement of MARCKS that coincided with the phosphorylation of MARCKS
      and the activation of both PKCepsilon and PKCalpha. Biochemical inhibition of PKC
      kinase activity and small interfering RNA (siRNA) against PKCepsilon demonstrated
      that PKCepsilon is indispensable for PDGF-BB-induced MARCKS phosphorylation and
      cell migration. Immunoprecipitation studies revealed an association between
      MARCKS and the PDGFbeta-receptor, while the PDGFbeta-receptor and PKCalpha
      associated with focal adhesion kinase (FAK). Transient transfection with MARCKS
      DNA plasmid remarkably reduced PDGF-BB stimulated cell motility. In contrast,
      siRNA against MARCKS increased cell migration in RNAi treated cells in comparison
      to the scrambled control cells. In conclusion, the present study indicates that
      MARCKS play a major key role in PDGF-BB-induced chemotaxis in activated hHSC.

PMID- 18329018
TI  - Retinal cells integrate into the outer nuclear layer and differentiate into
      mature photoreceptors after subretinal transplantation into adult mice.
AB  - Vision impairment caused by degeneration of photoreceptors, termed retinitis
      pigmentosa, is a debilitating condition with no cure presently available. Cell
      based therapeutic approaches represent one treatment option by replacing
      degenerating or lost photoreceptors. In this study the potential of transplanted
      primary retinal cells isolated from neonatal mice to integrate into the outer
      nuclear layer (ONL) of adult mice and to differentiate into mature photoreceptors
      was evaluated. Retinal cells were isolated from retinas of transgenic mice
      ubiquitously expressing enhanced green fluorescence protein (EGFP) at either
      postnatal day (P) 0, P1 or P4 and transplanted into the subretinal space of adult
      wild-type mice. One week to 11 months post-transplantation experimental retinas
      were analyzed for integration and differentiation of donor cells. Subsequent to
      transplantation some postnatal retinal cells integrated into the ONL of the host
      and differentiated into mature photoreceptors containing inner and outer segments
      as confirmed by immunohistochemistry and electron microscopy. Notably, the
      appearance of EGFP-positive photoreceptors was not the result of fusion between
      donor cells and endogenous photoreceptors. Retinal cells isolated at P4 showed a
      significant increase in their capacity to integrate into the ONL and to
      differentiate into mature photoreceptors when compared with cells isolated at P0
      or P1. As cell suspensions isolated at P4 are enriched in cells committed towards
      a rod photoreceptor cell fate it is tempting to speculate that immature
      photoreceptors may have the highest integration and differentiation potential and
      thus may present a promising cell type to develop cell replacement strategies for
      diseases involving rod photoreceptor loss.

PMID- 18329019
TI  - Unilateral subthalamic nucleus stimulation has a measurable ipsilateral effect on
      rigidity and bradykinesia in Parkinson disease.
AB  - BACKGROUND: Bilateral deep brain stimulation (DBS) of the subthalamic nucleus
      (STN) improves motor function in Parkinson disease (PD). However, little is known
      about the quantitative effects on motor behavior of unilateral STN DBS. METHODS:
      In 52 PD subjects with STN DBS, we quantified in a double-blinded manner rigidity
      (n=42), bradykinesia (n=38), and gait speed (n=45). Subjects were tested in four
      DBS conditions: both on, left on, right on and both off. A force transducer was
      used to measure rigidity across the elbow, and gyroscopes were used to measure
      angular velocity of hand rotations for bradykinesia. About half of the subjects
      were rated using the Unified Parkinson Disease Rating Scale (part III) motor
      scores for arm rigidity and repetitive hand rotation simultaneously during the
      kinematic measurements. Subjects were timed walking 25 feet. RESULTS: All
      subjects had significant improvement with bilateral STN DBS. Contralateral,
      ipsilateral and bilateral stimulation significantly reduced rigidity and
      bradykinesia. Bilateral stimulation improved rigidity more than unilateral
      stimulation of either side, but there was no significant difference between
      ipsilateral and contralateral stimulation. Although bilateral stimulation also
      increased hand rotation velocity more than unilateral stimulation of either side,
      contralateral stimulation increased hand rotation significantly more than
      ipsilateral stimulation. All stimulation conditions improved walking time but
      bilateral stimulation provided the greatest improvement. CONCLUSIONS: Unilateral
      STN DBS decreased rigidity and bradykinesia contralaterally as well
      ipsilaterally. As expected, bilateral DBS improved gait more than unilateral DBS.

PMID- 18329020
TI  - Expression, immunolocalization and serodiagnostic value of a myophilin-like
      protein from Schistosoma japonicum.
AB  - The cDNA of a Schistosoma japonicum myophilin-like protein was cloned, sequenced,
      and expressed in Escherichia coli as a recombined protein (rSj myophilin-like
      protein), and the protein was purified by affinity chromatography. The deduced
      amino acid sequences of the Sj myophilin-like protein showed significant homology
      to myophilin, calponin, Np22 and Mp20. Northern blot and RT-PCR analyzes revealed
      expression of the Sj myophilin-like protein mRNA in eggs, sporocysts, cercariae,
      hepatic schistosomula and adult worms. Confocal fluorescence microscopy localized
      the native protein to the muscle of the adult worm. In schistosome-infected
      rabbits, the rSj myophilin-like protein antibody level, assessed by ELISA, was
      elevated after infection but was reduced after praziquantel treatment. In humans,
      the myophilin-like protein antibody level was evaluated by ELISA in sera from 33
      non-infected humans and 61 schistosomiasis patients; the results showed a highly
      significant difference between the two groups with a sensitivity of 57.4%. Taken
      together, the myophilin-like protein may prove useful for monitoring the
      therapeutic effect of praziquantel rather than in serodiagnosis of
      schistosomiasis.

PMID- 18329021
TI  - Fasciola gigantica and Schistosoma mansoni: vaccine potential of recombinant
      glutathione S-transferase (rFgGST26) against infections in mice.
AB  - Recombinant Fasciola gigantica glutathione S-transferase (rFgGST26) was expressed
      in Escherichia coli. This protein had 86% and 56% sequence identity with 26 kDa
      GST from Fasciola hepatica and Schistosoma mansoni, respectively. Polyclonal
      antibody raised in ICR mice against rFgGST26 recognized immunoblotted 26 kDa
      native GSTs from F. gigantica and S. mansoni. rFgGST26 was used as a vaccine in
      combination with Freund's adjuvant to evaluate the induction of immune responses
      and protection against F. gigantica and S. mansoni infection in mice. Mice were
      immunized via subcutaneous (s.c.), intramuscular (i.m.) or intradermal (i.d.)
      routes. Strong protection (77-84%) against F. gigantica was observed in all
      routes. Immunization via s.c. route induced immune response with IgG1 isotype
      predominating, while i.m. and i.d. routes resulted in mixed IgG1/IgG2a immune
      responses. Passive intraperitoneal transfer of IgG1 predominating antisera from
      s.c. rFgGST26-immunized donors to naive recipient mice resulted in 47% protection
      against F. gigantica infection. This suggests that the mechanism of resistance
      depends on the presence of specific antibody against rFgGST26. Immunization with
      rFgGST26 via i.m. and i.d. routes resulted in significant cross protection (55%)
      against S. mansoni infection in the i.d. route with mixed IgG1/IgG2a response
      with IgG1 isotype predominating. This indicated that rFgGST26 is a good vaccine
      candidate against F. gigantica in mice and could also provide cross protection
      against S. mansoni.

PMID- 18329022
TI  - Haemonchus contortus: development of a two-step, differential-display PCR to
      detect differential gene expression in nematodes from immune and naive sheep.
AB  - Haemonchus contortus is a blood-feeding nematode which parasitizes the abomasum
      of sheep and represents a serious constraint to sheep production. Anthelmintics
      are currently the most common method of worm control but the worldwide
      development of multiple-drug resistance and issues of residues in the food chain
      make alternatives to anthelmintics a priority. Biotechnology-driven solutions to
      parasitism include vaccines and silencing of genes regulating nematode
      development. To pursue gene targets that may be suitable for parasite control, a
      two stage differential-display PCR (dd-PCR) approach was developed to observe
      differential gene expression between Haemonchus from immune and control sheep.
      Twenty-four reproducible differentially-expressed bands were identified in 60
      pairs of dd-PCR comparisons. The first of these cloned and sequenced corresponded
      to the H. contortus 60S ribosomal protein L35A. The remaining bands are being
      cloned and validated and may provide new targets for parasite control.

PMID- 18329023
TI  - Immunomodulatory mechanisms during Echinococcus granulosus infection.
AB  - The pathologic events that ensue after humans ingest the eggs of Echinococcus
      granulosus and continue while cystic echinococcosis develops, provide an
      excellent example illustrating the evasive strategies helminth parasites use to
      develop, progress and cause chronic disease. The hydatid cyst secretes and
      exposes numerous immunomodulatory molecules to the host's immune system. By
      characterizing these molecules we can understand the mechanisms that E.
      granulosus uses for increasing the efficiency and persistency of infection in the
      host. These molecules modulate both the innate and adaptive arms of the immune
      response and appear to target cellular and humoral responses. In this review, we
      discuss recent advances in the immunobiology of host-E. granulosus interactions
      that provide intriguing insights into the complex interplay between host and
      parasite that ultimately facilitates parasite survival.

PMID- 18329024
TI  - Ongoing twin pregnancy after rescue intracytoplasmic sperm injection of
      unfertilized abnormal oocytes.
AB  - OBJECTIVE: To report a case of an ongoing twin pregnancy resulting from rescue
      intracytoplasmic sperm injection (ICSI) after failed fertilization of
      morphologically abnormal oocytes. DESIGN: Case report. SETTING: Tertiary center
      for assisted reproductive technology (ART). PATIENT(S): A 28-year-old woman with
      primary infertility due to tubal obstruction. INTERVENTION(S): Rescue ICSI after
      failed IVF insemination. MAIN OUTCOME MEASURE(S): Clinical pregnancy. RESULT(S):
      Successful ongoing twin pregnancy. CONCLUSION(S): With failed fertilization of
      oocytes with abnormal morphology after IVF, early rescue ICSI may increase the
      fertilization rates and result in an ongoing pregnancy.

PMID- 18329025
TI  - Cholesterolosis of the common bile duct with anomalous arrangement of the
      pancreaticobiliary ductal system.

PMID- 18329026
TI  - Strongyloides stercoralis pancolitis in an immunocompetent patient.

PMID- 18329027
TI  - Intestinal tuberculosis in a patient on infliximab treatment.

PMID- 18329028
TI  - Mirizzi syndrome presenting as painless jaundice: a rare entity diagnosed by EUS.

PMID- 18329029
TI  - Melanosis ilei associated with chronic ingestion of edible charcoal.

PMID- 18329030
TI  - Death after PEG: results of the National Confidential Enquiry into Patient
      Outcome and Death.
AB  - BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is an accepted method of
      placing a feeding tube to enable enteral feeding in patients with swallowing
      difficulties. However, the factors associated with complications and death after
      PEG have not been studied in detail. We describe the largest audit of deaths
      after PEG tube insertion. OBJECTIVE: Our purpose was to determine the factors
      associated with death after PEG tube insertion. DESIGN: Deaths occurring within
      30 days after PEG tube insertion in the United Kingdom between April 2002 and
      March 2003 were identified and a questionnaire was sent to the consultant
      endoscopist for completion. PATIENTS: A total of 719 patients (391 male, median
      age 80 years, range 26-98 years) who died within 30 days after PEG insertion were
      identified for this study. SETTING: United Kingdom hospitals. MAIN OUTCOME
      MEASUREMENT: Cause of death. RESULTS: A total of 97% of the identified patients
      had coexistent neurologic disease. PEG tubes were inserted by specialized GI
      physicians in 522 cases (73%). Seventy-two patients (10%) required reversal
      agents after sedation. After PEG tube insertion, 309 patients (43%) died within 1
      week. Death was due to cardiovascular disease (n = 175), respiratory disease (n =
      508), central nervous system disease (n = 358), renal disease (n = 38), and
      hepatic failure (n = 11). In 136 cases (19%) the National Confidential Enquiry
      into Patient Outcome and Death expert panel regarded the procedure as futile.
      LIMITATIONS: Retrospective review of case records. CONCLUSIONS: Mortality and
      morbidity rates after PEG tube insertion are not insignificant. Selection of
      patients is paramount to good patient outcomes. Multidisciplinary team assessment
      should be performed on all patients being referred for PEG tube insertion.

PMID- 18329031
TI  - Neuroendocrine and behavioral responses to weak electric fields in adult sea
      lampreys (Petromyzon marinus).
AB  - We characterized the behavioral and neuroendocrine responses of adult sea
      lampreys (Petromyzon marinus) to weak electric fields. Adult sea lampreys,
      captured during upstream spawning migration, exhibited limited active behaviors
      during exposure to weak electric fields and spent the most time attached to the
      wall of the testing arena near the cathode (-). For adult male sea lampreys,
      exposure to weak electric fields resulted in increased lamprey (l) GnRH-I mRNA
      expression but decreased lGnRH-I immunoreactivities in the forebrain, and
      decreased Jun (a neuronal activation marker) mRNA levels in the brain stem.
      Similar effects were not observed in the brains of female sea lampreys after weak
      electric field stimulation. The influence of electroreception on forebrain lGnRH
      suggests that electroreception may modulate the reproductive systems in adult
      male sea lampreys. The changes in Jun expression may be associated with swimming
      inhibition during weak electric field stimulation. The results for adult sea
      lampreys are the opposite of those obtained using parasitic-stage sea lampreys,
      which displayed increased activity during and after cathodal stimulation. Our
      results demonstrate that adult sea lampreys are sensitive to weak electric
      fields, which may play a role in reproduction. They also suggest that electrical
      stimuli mediate different behaviors in feeding-stage and spawning-stage sea
      lampreys.

PMID- 18329032
TI  - The neuroplastic maternal brain.

PMID- 18329033
TI  - Preparation of silica-magnetite nanoparticle mixed hemimicelle sorbents for
      extraction of several typical phenolic compounds from environmental water
      samples.
AB  - A novel type of superparamagnetic silica-coated (Fe3O4/SiO2 core/shell) magnetite
      nanoparticle modified by surfactants has been successfully synthesized and was
      applied as an effective sorbent material for the pre-concentration of several
      typical phenolic compounds (bisphenol A (BPA), 4-tert-octylphenol (4-OP) and 4-n
      nonylphenol (4-NP)) from environmental water samples. Compared with pure magnetic
      particles, a thin and dense silica layer would protect the iron oxide core from
      leaching out in acidic conditions. In order to enhance their adsorptive tendency
      towards organic compounds, cetylpyridinium chloride (CPC) or
      cetyltrimethylammonium bromide (CTAB) were added, which adsorbed on the surface
      of the Fe3O4/SiO2 nanoparticles (Fe3O4/SiO2 NPs) and formed mixed hemimicelles.
      Main factors affecting the adsolubilization of analytes were optimized and
      comparative study on the use of CPC and CTAB-coated Fe3O4/SiO2 NPs mixed
      hemimicelles-based SPE was also carried out. CPC-coated Fe3O4/SiO2 NPs system was
      selected due to lower elution volume required and more effective adsorption of
      the target compounds. Under selected conditions, concentration factor of 1600 was
      achieved by using this method to extract 800 mL of different environmental water
      samples. The detection limits obtained for BPA, 4-OP and 4-NP with HPLC-FLD were
      7, 14, and 20 ng/L, respectively.

PMID- 18329034
TI  - Separation of capsaicin from capsaicinoids by simulated moving bed
      chromatography.
AB  - Capsaicinoids were separated from capsicum oleoresin by solvent extraction and
      adsorption separation on macropore resin, and used directly as the feed of
      simulated moving bed. Using a mobile phase of methanol/water (75/25, v/v) and ODS
      columns, the two key components, capsaicin and dihydrocapsaicin, were separated
      completely, while part of minor weak impurities were discarded by forcing them to
      leak into zone I. The amount of discarded impurities increases with decreasing
      flow rate in zone I so that the purity of capsaicin in raffinate stream could be
      improved.

PMID- 18329035
TI  - Simplified sample preparation method for triclosan and methyltriclosan
      determination in biota and foodstuff samples.
AB  - An improved method for the determination of triclosan (TCS) and methyltriclosan
      (MTCS) in fish and foodstuff samples is presented. Analytes were simultaneously
      extracted and purified using the matrix solid-phase dispersion (MSPD) technique,
      and then selectively determined by gas chromatography with tandem mass
      spectrometry (GC-MS/MS). Several combinations of dispersants, clean-up co
      sorbents and extraction solvents were tested in order to obtain lipid-free
      extracts and quantitative recoveries for TCS and MTCS. Under optimised
      conditions, 0.5 g samples were dispersed using 1.5 g of neutral silica in a
      mortar with a pestle, and transferred to a polypropylene cartridge containing 3 g
      of silica impregnated with 10% of sulphuric acid (SiO2-H2SO4, 10%, w/w). Analytes
      were recovered with 10 mL of dichloromethane whereas lipids were oxidized in the
      layer of acidic silica. The extract was concentrated to dryness and re
      constituted with 1 mL of ethyl acetate. Then, a fraction of 0.5 mL was mixed with
      50 microL of N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA) and
      injected in the GC-MS/MS system. The developed method provided absolute
      recoveries between 77 and 120% for different samples spiked at the low ng g(-1)
      level, quantification limits in the range of 1-2 ng g(-1) and a considerable
      simplicity in comparison with previously developed sample preparation approaches.
      Experiments carried out placing sliced food samples in direct contact with TCS
      treated kitchenware surfaces showed the capability of the biocide to migrate into
      foodstuffs.

PMID- 18329036
TI  - Effects of anionic surfactants on ligand-promoted dissolution of iron and
      aluminum hydroxides.
AB  - We investigated the influence of the surfactants sodium dodecyl sulfate (SDS) and
      rhamnolipid (RhL) on ligand-promoted dissolution of goethite (alpha-FeOOH) and
      boehmite (gamma-AlOOH) at pH 6. The siderophore desferrioxamine B (DFOB), its
      derivate desferrioxamine D (DFOD), ethylenediaminetetraacetic acid (EDTA), and 8
      hydroxyquinoline-5-sulfonic acid (HQS) were used as ligands. The rates of ligand
      promoted dissolution of goethite were significantly increased in the presence of
      low concentrations of anionic surfactants (<80 microM SDS; <6 mg/L RhL). At
      higher surfactant concentrations, however, the effects of surfactants were
      negligible. The dissolution rates in the presence of surfactants were not
      correlated with adsorbed amounts of ligands. Three possible factors contributing
      to these observations were further investigated and discussed: (i) adsorbed
      surfactants may influence ligand adsorption by changes in the ligand's surface
      speciation, (ii) re-adsorption of Fe-DFOB or Fe-DFOD complexes may lead to an
      underestimation of siderophore-promoted dissolution rates at high surfactant
      concentrations, and (iii) co-adsorption of protons to goethite with SDS may
      influence the dissolution rates. However, our results show that none of these
      three factors can satisfactorily explain the observed effects of anionic
      surfactants on ligand-promoted dissolution rates of iron and aluminum hydroxides.

PMID- 18329037
TI  - Toward a comprehensive view of the skills involved in word reading in Grades 4,
      6, and 8.
AB  - Research to date has proposed four main variables involved in reading
      development: phonological awareness, naming speed, orthographic knowledge, and
      morphological awareness. Although each of these variables has been examined in
      the context of one or two of the other variables, this study examines all four
      factors together to assess their unique contribution to reading. A sample of
      children in Grades 4, 6, and 8 (ages 10, 12, and 14 years) completed a battery of
      tests that included at least one measure of each of the four variables and two
      measures of reading accuracy. Phonological awareness, orthographic knowledge, and
      morphological awareness each contributed uniquely to real word and pseudoword
      reading beyond the other variables, whereas naming speed did not survive these
      stringent controls. The results support the sustained importance of these three
      skills in reading by older readers.

PMID- 18329038
TI  - Towards a FRET-based immunosensor for continuous carbohydrate monitoring.
AB  - In this report we have evaluated the potential of using fluorescence/Forster
      resonance energy transfer (FRET) in a competitive immunosensor for continuous
      monitoring of the carbohydrate hapten maltose. The cyanine dyes Cy5 and Cy5.5
      were used as a donor-acceptor pair by conjugation to maltose-labeled bovine serum
      albumin (BSA) and the monoclonal antibody IgG 39.5, giving Cy5-BSA-maltotriitol
      (3.1/1/18) and Cy5.5-mAb39.5 (2.2/1), respectively. This antibody with weak
      affinity towards maltose showed full reversibility to both the free maltose and
      the maltose-labeled conjugate. It allowed us to measure continuously the maltose
      content by monitoring the FRET signal change over time due to displacement of Cy5
      BSA-maltotriitol from Cy5.5-mAb39.5 inside a semipermeable capsule. A near 22%
      total increase was seen in the fluorescence intensity ratio I(670)/I(700) in the
      presence of maltose, with a calculated EC(50)=1.87+/-0.13 mM (R(2)=0.9984) from
      the sigmoidal dose-response curve at 25 degrees C. Specificity of the
      immunosensor was shown with the structural analog to maltose, cellobiose, and it
      generated no detectable response. A minor drift in the sensor baseline was seen
      with 0.4% per 24 h, which was in the same magnitude as the signal-to-noise ratio,
      during the 4 weeks of measurements. The immunosensor was applied to crude samples
      of oat drinks for direct quantification of the maltose content. Overall, this
      work demonstrates the potential to use an immunosensor based on weakly binding
      antibodies and FRET technology for remote and non-invasive carbohydrate
      monitoring.

PMID- 18329039
TI  - The role of NHE-1 in myocardial hypertrophy and remodelling.
AB  - Na-H exchange (NHE) is the primary process by which the cardiac cell extrudes
      protons particularly under conditions of intracellular acidosis. Nine isoforms of
      NHE have now been identified. Although these antiporters are expressed in
      virtually all tissues, cardiac cells posses primarily the ubiquitous NHE-1
      subtype. It has been well established that NHE-1 is a major contributor to acute
      ischemic and reperfusion injury although it is now emerging that NHE-1
      contributes to chronic maladaptive myocardial responses to injury such as post
      infarction myocardial remodelling and likely contributes to the development of
      heart failure. Experimental studies using both in vitro approaches as well as
      animal models of heart failure have consistently demonstrated a beneficial effect
      of NHE-1 inhibitors in attenuating hypertrophy in response to various stimuli as
      well as inhibiting heart failure in a variety of animal models representing
      experimentally-induced or genetic models of heart failure. The beneficial effects
      of NHE-1 inhibitors occur independently of infarct size reduction or on any
      direct effects on afterload thus implicating a direct antiremodelling influence
      of these agents. It is proposed that NHE-1 inhibition represents a potentially
      effective new therapeutic approach for the treatment of heart failure.

PMID- 18329040
TI  - Negative regulation of beta-adrenergic function by hydrogen sulphide in the rat
      hearts.
AB  - Beta-adrenoceptor is over-stimulated during myocardial ischemia, in which
      hydrogen sulphide (H2S) concentration was found to be lowered. The present study
      attempted to investigate if H2S modulates beta-adrenoceptor function and the
      underlying mechanism. We examined the effect of NaHS (a H2S donor) on myocyte
      contraction and electrically-induced (EI) intracellular calcium ([Ca2+](i))
      transients upon beta-adrenergic stimulation in rat ventricular myocytes with a
      video edge tracker method and a spectrofluorometric method using fura-2/AM as a
      calcium indicator, respectively. We found that isoproterenol (ISO, 10(-9)-10(-6)
      M), a beta-adrenoceptor agonist, concentration-dependently increased the twitch
      amplitude of ventricular myocytes, which was attenuated by NaHS (10(-5)-10(-3) M)
      in a dose-dependent manner. The amplitudes and maximal velocities (+/-dl/dt) of
      myocyte twitch and EI-[Ca2+](i) transient amplitudes were enhanced by ISO,
      forskolin (an adenylyl cyclase activator), 8-bromoadenosine-3',5'-cyclic
      monophosphate (an activator of protein kinase A) and Bay K-8644 (a selective L
      type Ca2+ channel agonist). Administration of NaHS (100 microM) only
      significantly attenuated the effects of ISO and forskolin. Moreover, NaHS
      reversed ISO-induced cAMP elevation and forskolin-stimulated adenylyl cyclase
      activity. In addition, stimulation of beta-adrenoceptor by ISO significantly
      decreased endogenous H2S production in rat ventricular myocytes. In conclusion,
      H2S may negatively modulate beta-adrenoceptor function via inhibiting adenylyl
      cyclase activity. Impairment of this negative modulation during ischemia may
      induce cardiac arrhythmias. Our study may provide a novel mechanism for ischemia
      induced cardiac injury.

PMID- 18329041
TI  - Evolution of class-specific peptides targeting a hot spot of the Galphas subunit.
AB  - The four classes of heterotrimeric G-protein alpha subunits act as molecular
      routers inside cells, gating signals based on a bound guanosine nucleotide
      (guanosine 5'-triphosphate versus guanosine 5'-diphosphate). Ligands that
      specifically target individual subunits provide new tools for monitoring and
      modulating these networks, but are challenging to design due to the high sequence
      homology and structural plasticity of the Galpha-binding surface. Here we have
      created an mRNA display library of peptides based on the short Galpha-modulating
      peptide R6A-1 and selected variants that target a convergent protein-binding
      surface of Galphas.guanosine 5'-diphosphate. After selection/evolution, the most
      Galphas-specific peptide, Galphas(s)-binding peptide (GSP), was used to design a
      second-generation library, resulting in several new affinity- and selectivity
      matured peptides denoted as mGSPs. The two-step evolutionary walk from R6A-1 to
      mGSP-1 resulted in an 8000-fold inversion in binding specificity, altered seven
      out of nine residues in the starting peptide core, and incorporated both positive
      and negative design steps. The resulting mGSP-1 peptide shows remarkable
      selectivity and affinity, exhibiting little or no binding to nine homologous
      Galpha subunits or human H-Ras, and even discriminates the Galphas splice variant
      Galphas(l). Selected peptides make specific contacts with the effector-binding
      region of Galpha, which may explain an interesting bifunctional activity observed
      in GSP. Overall, our work demonstrates a design of simple, linear, highly
      specific peptides that target a protein-binding surface of Galphas and argues
      that mRNA display-based selection/evolution is a powerful route for targeting
      protein families with high class specificity and state specificity.

PMID- 18329042
TI  - Crystal structure of human epidermal kallikrein 7 (hK7) synthesized directly in
      its native state in E. coli: insights into the atomic basis of its inhibition by
      LEKTI domain 6 (LD6).
AB  - Human kallikrein 7, a major protease of human skin, has been synthesized directly
      in its native conformation in Escherichia coli by forcing the secretion of the
      newly synthesized polypeptide into the bacterial periplasm. The procedure yields
      a stable kallikrein 7 with highly specific activity that is inhibited efficiently
      by its specific inhibitor LEKTI domain 6. The protein was crystallized, and its
      three-dimensional structure was solved in the absence of protease inhibitors. The
      structure obtained agrees with that reported recently for human tissue kallikrein
      7 crystallized in the presence of protease inhibitors from a preparation obtained
      in a baculovirus protein expression system. A model of the interaction between
      the protease and its inhibitor is proposed on the basis of both the three
      dimensional structure of human tissue kallikrein 7 reported here and that of the
      LEKTI domain 6 solved previously by NMR.

PMID- 18329043
TI  - Fibril formation of hsp10 homologue proteins and determination of fibril core
      regions: differences in fibril core regions dependent on subtle differences in
      amino acid sequence.
AB  - Heat shock protein 10 (hsp10) is a member of the molecular chaperones and works
      with hsp60 in mediating various protein folding reactions. GroES is a
      representative protein of hsp10 from Escherichia coli. Recently, we found that
      GroES formed a typical amyloid fibril from a guanidine hydrochloride (Gdn-HCl)
      unfolded state at neutral pH. Here, we report that other hsp10 homologues, such
      as human hsp10 (Hhsp10), rat mitochondrial hsp10 (Rhsp10), Gp31 from T4 phage,
      and hsp10 from the hyperthermophilic bacteria Thermotoga maritima, also form
      amyloid fibrils from an unfolded state. Interestingly, whereas GroES formed
      fibrils from either the Gdn-HCl unfolded state (at neutral pH) or the acidic
      unfolded state (at pH 2.0-3.0), Hhsp10, Rhsp10, and Gp31 formed fibrils from only
      the acidic unfolded state. Core peptide regions of these protein fibrils were
      determined by proteolysis treatment followed by a combination of Edman
      degradation and mass spectroscopy analyses of the protease-resistant peptides.
      The core peptides of GroES fibrils were identical for fibrils formed from the Gdn
      HCl unfolded state and those formed from the acidic unfolded state. However, a
      peptide with a different sequence was isolated from fibrils of Hhsp10 and Rhsp10.
      With the use of synthesized peptides of the determined core regions, it was also
      confirmed that the identified regions were capable of fibril formation. These
      findings suggested that GroES homologues formed typical amyloid fibrils under
      acidic unfolding conditions but that the fibril core structures were different,
      perhaps owing to differences in local amino acid sequences.

PMID- 18329044
TI  - Small-angle X-ray scattering of reduced ribonuclease A: effects of solution
      conditions and comparisons with a computational model of unfolded proteins.
AB  - The disulfide-reduced form of bovine ribonuclease A, with the Cys thiols
      irreversibly blocked, was characterized by small-angle x-ray scattering. To help
      resolve the conflicting results and interpretations from previous studies of this
      model unfolded protein, we measured scattering profiles using a range of solution
      conditions and compared them with the profiles predicted by a computational model
      for a random-coil polypeptide. Analysis of the simulated and experimental
      profiles reveals that scattering intensities at intermediate angles,
      corresponding to interatomic distances in the range of 5-20 A, are particularly
      sensitive to changes in solvation and can be used to assess the internal scaling
      behavior of the polypeptide chain, expressed as a mass fractal dimension, D(m).
      This region of the scattering curve is also much less sensitive to experimental
      artifacts than is the very small angle regime (the Guinier region) that has been
      more typically used to characterize unfolded proteins. The experimental small
      angle x-ray scattering profiles closely matched those predicted by the
      computational model assuming relatively small solvation energies. The scaling
      behavior of the polypeptide approaches that of a well-solvated polymer under
      conditions where it has a large net charge and at high urea concentrations. At
      lower urea concentrations and neutral pH, the behavior of the chain approaches
      that expected for theta-conditions, where the effects of slightly unfavorable
      interactions with solvent balance those of excluded volume, leading to scaling
      behavior comparable to that of an idealized random walk chain. Though detectable,
      the shift toward more compact conformations at lower urea concentrations does not
      correspond to a transition to a globule state and is associated with little or no
      reduction in conformational entropy. This type of collapse, therefore, is
      unlikely to greatly reduce the conformational search for the native state.

PMID- 18329045
TI  - Farnesylation of the SNARE protein Ykt6 increases its stability and helical
      folding.
AB  - The evolutionarily conserved soluble N-ethylmaleimide-sensitive factor attachment
      protein receptor (SNARE) proteins are involved in the fusion of vesicles with
      their target membranes. While most SNAREs are permanently anchored to membranes
      by their transmembrane domains, the vesicle-associated SNARE Ykt6 has been found
      both in soluble and in membrane-bound pools. The R-SNARE Ykt6 is thought to
      mediate interactions between various Q-SNAREs by a reversible membrane-targeting
      cycle. Membrane attachment of Ykt6 is achieved by its C-terminal prenylation and
      palmitoylation motif succeeding the SNARE motif. In this study, we have analyzed
      full-length farnesylated Ykt6 from yeast and humans by biochemical and structural
      means. In vitro farnesylation of the C-terminal CAAX box of recombinant full
      length Ykt6 resulted in stabilization of the native protein and a more compactly
      folded structure, as shown by size exclusion chromatography and limited
      proteolysis. Circular dichroism spectroscopy indicated a specific increase in the
      helical content of the farnesylated Ykt6 compared to the nonlipidated form or the
      single-longin domain, which correlated with a marked increase in stability as
      observed by heat denaturation experiments. Although highly soluble, farnesylated
      Ykt6 is capable of lipid membrane binding independent of the membrane charge, as
      shown by surface plasmon resonance. The crystal structure of the N-terminal
      longin domain of yeast Ykt6 (1-140) was determined at 2.5 A resolution. As
      similarly found in a previous NMR structure, the Ykt6 longin domain contains a
      hydrophobic patch at its surface that may accommodate the lipid moiety. In the
      crystal structure, this hydrophobic surface is buried in a crystallographic
      homomeric dimer interface. Together, these observations support a previously
      suggested closed conformation of cytosolic Ykt6, where the C-terminal farnesyl
      moiety folds onto a hydrophobic groove in the N-terminal longin domain.

PMID- 18329046
TI  - Dopaminergic receptor D5 mRNA expression is increased in circulating lymphocytes
      of Tourette syndrome patients.
AB  - Tourette syndrome (TS) is a neuropsychiatric disorder in which dopaminergic
      dysfunction and immune system abnormalities seem to coexist. Using real-time PCR,
      we determined mRNA expression of dopamine receptors (DRs) D1-5 in peripheral
      blood lymphocytes (PBLs) from 15 TS patients and 15 sex- and age-matched healthy
      controls (HCs). DRD5 mRNA levels in cells from TS were higher than in cells from
      HCs. In TS patients with obsessive-compulsive disorder, DRD5 mRNA levels in PBLs
      showed a highly positive correlation with the severity of compulsive symptoms.
      DRD5 mRNA upregulation in PBLs from TS patients may represent a peripheral marker
      of dopaminergic dysfunction and supports the involvement of the immune system in
      TS.

PMID- 18329047
TI  - Analysis and IbM simulation of the stages in bacterial lag phase: basis for an
      updated definition.
AB  - The lag phase is the initial phase of a culture that precedes exponential growth
      and occurs when the conditions of the culture medium differ from the pre
      inoculation conditions. It is usually defined by means of cell density because
      the number of individuals remains approximately constant or slowly increases, and
      it is quantified with the lag parameter lambda. The lag phase has been studied
      through mathematical modelling and by means of specific experiments. In recent
      years, Individual-based Modelling (IbM) has provided helpful insights into lag
      phase studies. In this paper, the definition of lag phase is thoroughly examined.
      Evolution of the total biomass and the total number of bacteria during lag phase
      is tackled separately. The lag phase lasts until the culture reaches a maximum
      growth rate both in biomass and cell density. Once in the exponential phase, both
      rates are constant over time and equal to each other. Both evolutions are split
      into an initial phase and a transition phase, according to their growth rates. A
      population-level mathematical model is presented to describe the transitional
      phase in cell density. INDividual DIScrete SIMulation (INDISIM) is used to check
      the outcomes of this analysis. Simulations allow the separate study of the
      evolution of cell density and total biomass in a batch culture, they provide a
      depiction of different observed cases in lag evolution at the individual-cell
      level, and are used to test the population-level model. The results show that the
      geometrical lag parameter lambda is not appropriate as a universal definition for
      the lag phase. Moreover, the lag phase cannot be characterized by a single
      parameter. For the studied cases, the lag phases of both the total biomass and
      the population are required to fully characterize the evolution of bacterial
      cultures. The results presented prove once more that the lag phase is a complex
      process that requires a more complete definition. This will be possible only
      after the phenomena governing the population dynamics at an individual level of
      description, and occurring during the lag and exponential growth phases, are well
      understood.

PMID- 18329048
TI  - Ecological balance in the native population dynamics may cause the paradox of
      pest control with harvesting.
AB  - We analyze a time-discrete mathematical model of host-parasite population
      dynamics with harvesting, in which the host can be regarded as a pest. We harvest
      a portion of the host population at a moment in each parasitism season. The
      principal target of the harvesting is the host; however, the parasite population
      may also be affected and reduced by a portion. Our model involves the Beverton
      Holt type density effect on the host population. We investigate the condition in
      which the harvesting of the host results in an eventual increase of its
      equilibrium population size, analytically proving that the paradoxical increase
      could occur even when the harvesting does not directly affect the parasite
      population at all. We show that the paradox of pest control could be caused
      essentially by the interspecific relationship and the intraspecific density
      effect.

PMID- 18329049
TI  - Cerebral perfusion pressure in giraffe: modelling the effects of head-raising and
      -lowering.
AB  - Loss of consciousness caused by positional changes of the head results from
      reduced cerebral blood flow (CBF). CBF is related to cerebral perfusion pressure
      (CPP). CPP is the difference between mean arterial pressure (MAP) at the head and
      intracranial pressure (ICP). The positional change of the giraffe head between
      ground level and standing upright is the largest of all animals yet loss of
      consciousness does not occur. We have investigated the possibility that an
      increase in CPP protects giraffe from fainting, using a mechanical model that
      functioned as an anatomical U-tube. It consisted of a rigid ascending "carotid"
      limb, a collapsible "brain" tube drained by a rigid, "vertebral venous plexus"
      (VVP) tube, and a collapsible "head" tube drained by a collapsible tube
      representing the "jugular vein". The descending tubes could be rotated relative
      to the "carotid" tube to be horizontal, or at 30 degrees , 45 degrees , and 60
      degrees to the vertical to simulate changes in head position. Pressure at the top
      of the "carotid" tube was intracranial MAP, at the top of the "VVP" tube was ICP,
      and the difference CPP. In the simulated "head-up" position and a fluid flow rate
      of 4 L min(-1), CPP was approximately 170 mmHg. With the VVP tube horizontal, CPP
      fell from approximately 170 to 45 mmHg, but increased to approximately 67 mmHg at
      30 degrees "down", to approximately 70 mmHg at 45 degrees "down" and to
      approximately 75 at 60 degrees "down". The fall in CPP in the head-down positions
      resulted from a decrease in viscous resistance in, and dissipation of pressure
      to, the "head" and "jugular" tubes. These data provide an estimate of cranial
      pressure changes in giraffe during positional changes of the head, and suggest
      that an increase in CPP plays a significant role in maintaining CBF during head
      raising and that it may be an important mechanism for preventing fainting in
      giraffe.

PMID- 18329050
TI  - Phosphorus retention and release by sediments in the eutrophic Mai Po Marshes,
      Hong Kong.
AB  - This study examined the phosphorus retention and release characteristics of
      sediments in the eutrophic Mai Po Marshes in Hong Kong. Results of chemical
      fractionation show that the sum of inorganic P pools exceeded 50% of the total
      sediment P content, with the redox-sensitive iron-bound P (Fe(OOH) approximately
      P) being the dominant P fraction. Given the considerable average Fe(OOH)
      approximately P concentration of 912 microg g(-1), Mai Po sediments demonstrated
      a great potential to release bioavailable P under low sediment redox potentials.
      This was further supported by the high mean anaerobic P flux of 31.8 mg m(-2)d(
      1) recorded in Mai Po sediment cores, indicating the role of bottom sediments as
      a net P source. Although sediments in Mai Po had appreciable Langmuir adsorption
      maxima (1642-3582 mg kg(-1)), the high zero equilibrium P concentrations (0.02
      0.51 mg L(-1)) obtained suggest that sediment sorption processes would contribute
      to sustaining the eutrophic conditions in overlying water column even with a
      further reduction in external P load. Concerted efforts should be made to reduce
      internal loading of P, especially under reducing conditions, to complement the
      implementation of zero discharge policy for Deep Bay for effective eutrophication
      abatement and long-term water quality improvement in the Mai Po Marshes.

PMID- 18329051
TI  - [Intracranial hypotension with subdural hematoma following lumbar puncture: case
      report].
AB  - BACKGROUND AND PURPOSE: Lumbar puncture is a common procedure highly contributive
      to neurological diagnosis. It can also cause serious adverse side effects
      including subdural hematoma and intracranial hypotension as illustrated by this
      case report. CASE REPORT: A 38-year-old women presented severe intracranial
      hypotension after a lumbar puncture. Magnetic resonance imaging was compatible
      with intracranial hypotension and revealed an acute subdural hematoma with
      midline deviation. A first blood patch was unsuccessful. Symptom relief was
      achieved with a second patch. The patient was, then, discharged but developed
      recurrent headache subsequent to the transformation from acute to chronic
      subdural hematoma. Surgical drainage was required. The postoperative imaging and
      physical examination returned to normal and the patient was discharged with no
      recurrence. CONCLUSION: The serious adverse effects of lumbar puncture is an easy
      and common medical procedure that must be kept in mind.

PMID- 18329052
TI  - Functional lipidomics. Calcium-independent activation of
      endocannabinoid/endovanilloid lipid signalling in sensory neurons by protein
      kinases C and A and thrombin.
AB  - N-arachidonoylethanolamine (anandamide, AEA), is a full agonist at both
      cannabinoid CB(1) receptors and "transient receptor potential vanilloid" type 1
      (TRPV1) channels, and N-palmitoylethanolamine (PEA) potentiates these effects. In
      neurons of the rat dorsal root ganglia (DRG), TRPV1 is activated and/or
      sensitised by AEA as well as upon activation of protein kinases C (PKC) and A
      (PKA). We investigated here the effect on AEA levels of PKC and PKA activators in
      DRG neurons. AEA levels were significantly enhanced by both phorbol-miristoyl
      acetate (PMA), a typical PKC activator, and forskolin (FSK), an adenylate cyclase
      stimulant, as well as by thrombin, which also activates PKC by stimulating
      protease-activated receptors (PARs). The levels of the other endocannabinoid and
      TRPV1-inactive compound, 2-arachidonoylglycerol (2-AG), were enhanced only by
      thrombin and to a lesser extent than AEA, whereas PEA was not affected by any of
      the treatments. Importantly, FSK- and PMA-induced elevation of AEA levels was not
      sensitive to intracellular Ca2+ chelation with BAPTA-acetoxymethyl (AM) ester. In
      human embryonic kidney (HEK-293) cells, which constitutively express PARs,
      thrombin, PMA and FSK elevated AEA levels, and the effects of the two former
      compounds were counteracted by the PKC inhibitor, RO318220, whereas the effect of
      FSK was reduced by the PKA inhibitor RpcAMPs. In conclusion, we report that AEA
      levels are stimulated by both PKC, either directly or after thrombin receptor
      activation, and PKA, possibly in a way independent from intracellular calcium.
      Since AEA activates TRPV1, these findings may suggest the existence of an
      amplificatory cascades on this receptor in sensory neurons.

PMID- 18329053
TI  - Sex-dependent effects of periadolescent exposure to the cannabinoid agonist CP
      55,940 on morphine self-administration behaviour and the endogenous opioid
      system.
AB  - Early cannabinoid consumption may predispose individuals to the misuse of
      addictive drugs later in life. However, there is a lack of experimental evidence
      as to whether cannabinoid exposure during adolescence might differently affect
      opiate reinforcing efficacy and the opioid system in adults of both sexes. Our
      aim was to examine whether periadolescent chronic exposure to the cannabinoid
      agonist CP-55,940 could exert sex-dependent effects on morphine reinforcing and
      the opioid system in adulthood. Morphine reinforcing was studied under a
      progressive ratio (PR) reinforcement schedule in adult male and female rats that
      previously acquired morphine self-administration under a fixed ratio 1 (FR1)
      schedule. Binding levels and functionality of mu-opioid receptors were also
      evaluated. Periadolescent cannabinoid exposure altered morphine self
      administration and the opioid system in adult rats in a sex-dependent manner. CP
      55,940-exposed males exhibited higher self-administration rates under a FR1, but
      not under a PR schedule. In females, CP-55,940 did not modify morphine self
      administration under either schedule. Moreover, CP-55,940 also increased mu
      opioid receptor levels in the subcallosal streak of pre-treated animals and
      decreased mu-opioid receptor functionality in the nucleus accumbens shell but
      again, only in males. Our data indicate that adult male rats exposed to the
      cannabinoid in adolescence self-administer more morphine than females, but only
      when the demands required by the schedule of reinforcement are low, which might
      be related to the decrease in mu-opioid receptor functionality in the NAcc-shell
      observed in these animals.

PMID- 18329054
TI  - The cyclooxygenase-2/prostaglandin E2 pathway is involved in the somatostatin
      induced decrease of epileptiform bursting in the mouse hippocampus.
AB  - The neuromodulatory peptide somatostatin-14 (SRIF) plays an important inhibitory
      role in epilepsy, but little is known on the signalling mechanisms coupled to
      this effect of SRIF. We have previously demonstrated that SRIF induces reduction
      of epileptiform bursting in a model of interictal-like activity in mouse
      hippocampal slices. In this same model, we investigated whether the
      cyclooxygenase 2 (COX-2)/prostaglandin E(2) (PGE(2)) pathway is part of those
      signalling mechanisms mediating SRIF anti-epileptic actions. Both the expression
      of COX-2 (mRNA and protein) and the endogenous release of PGE(2) increased in
      concomitance with epileptiform bursting. In particular, COX-2 protein increased
      in CA1/CA3 pyramidal layer and in the granular layer of the dentate gyrus. In
      addition, the selective inhibition of COX-2 by NS-398 markedly decreased
      endogenous PGE(2) release induced by epileptiform bursting and the epileptiform
      bursting itself. Similar effects on epileptiform bursting were obtained with
      another COX-2 inhibitor, i.e., meloxicam. SRIF application counteracted the
      increase of both COX-2 expression and PGE(2) release which occurred in
      concomitance with epileptiform bursting. Interestingly, SRIF and NS-398
      comparably reduced epileptiform bursting in a non-additive manner and PGE(2)
      abolished the inhibitory effect of SRIF on epileptiform bursting. These results
      demonstrate that: i) the COX-2/PGE(2) pathway facilitates epileptiform bursting;
      and ii) SRIF exerts an anti-epileptic role by coupling to the COX-2/PGE(2)
      pathway. In conclusion, we have identified a key set of signalling events that
      underlie anti-convulsant effects of SRIF in a mouse model of hippocampal
      bursting, thus providing useful data not only to identify alternative
      intervention points for the modulation of SRIF function, but also to exploit new
      chemical space for drug-like molecules.

PMID- 18329055
TI  - Disruption of temporal processing in a subject with probable frontotemporal
      dementia.
AB  - Previous research suggests that the frontal lobes are essential for temporal
      processing. We report a patient, MN, with probable frontotemporal dementia (FTD)
      who was tested on a battery of timing tasks with stimuli in the sub- and supra
      second range. MN demonstrated a substantial over-estimation and under-production
      of target intervals on estimation and production tasks respectively but was as
      accurate as controls on a reproduction task. Furthermore, this deficit was
      markedly different for auditory and visual stimuli on production and estimation
      tasks; estimates of the duration of auditory stimuli were three to four times
      longer than for comparable visual stimuli. She performed normally on a task
      requiring her to judge whether a stimulus was longer or shorter than a standard
      duration with both sub- and supra-second stimuli. She performed well on control
      tasks involving estimation, production and reproduction of line lengths
      suggesting that her deficits were not attributable to a generalized cognitive
      impairment or an inability to make magnitude judgments. These data suggest that
      bifrontal pathology disrupts the "clock" or memory for time.

PMID- 18329056
TI  - Left hemisphere specialization for duration discrimination of musical and speech
      sounds.
AB  - Hemispheric asymmetries for processing duration of non-verbal and verbal sounds
      were investigated in 60 right-handed subjects. Two dichotic tests with attention
      directed to one ear were used, one with complex tones and one with consonant
      vowel syllables. Stimuli had three possible durations: 350, 500, and 650 ms.
      Subjects judged whether the duration of a probe was same or different compared to
      the duration of the target presented before it. Target and probe were part of two
      dichotic pairs presented with 1s interstimulus interval and occurred on the same
      side. Dependent variables were reaction time and accuracy. Results showed a
      significant right ear advantage for both dependent variables with both complex
      tones and consonant-vowel syllables. This study provides behavioural evidence of
      a left hemisphere specialization for duration perception of both musical and
      speech sounds in line with the current view based on a parameter--rather than
      domain-specific structuring of hemispheric perceptual asymmetries.

PMID- 18329057
TI  - Lack of polarization optomotor response in the cuttlefish Sepia elongata
      (d'Orbigny, 1845).
AB  - Polarization sensitivity is a characteristic of the visual system of cephalopods.
      In cuttlefish, it has been particularly well documented in Sepia officinalis. We
      examined the response of a little studied cuttlefish species, S. elongata,
      towards a moving, vertically-oriented grating (contrasting and polarized stripes)
      using an optomotor response apparatus. We also examined the arrangement of the
      photoreceptors in the retina. Cuttlefish responded to patterns of contrasting
      stripes but not to a pattern of polarized stripes, although the optical
      structures that could allow polarization sensitivity were found in their retinas.
      These results suggest that intensity information and polarization information are
      perceived differently by cuttlefish.

PMID- 18329058
TI  - Non-volatile floral oils of Diascia spp. (Scrophulariaceae).
AB  - The floral oils of Diascia purpurea, Diascia vigilis, Diascia cordata, Diascia
      megathura, Diascia integerrima and Diascia barberae (Scrophulariaceae) were
      selectively collected from trichome elaiophores. The derivatized floral oils were
      analyzed by gas chromatography-mass spectrometry (GC-MS), whilst the
      underivatized samples were analysed by electrospray ionization mass spectrometry
      (ESI-MS) and Fourier-transform ion cyclotron resonance mass spectrometry (FTICR
      MS). The most common constituents of the floral oils investigated are partially
      acetylated acylglycerols of (3R)-acetoxy fatty acids (C(14), C(16), and C(18)),
      as was proven with non-racemic synthetic reference samples. The importance of
      these oils for Rediviva bees is discussed in a co-evolutionary context.

PMID- 18329059
TI  - Bullatenone, 1,3-dione and sesquiterpene chemotypes of Lophomyrtus species.
AB  - The only known natural source of the volatile bioactive compounds bullatenone 1
      and 4-methyl-1-phenylpentane-1,3-dione 2 is the New Zealand endemic shrub
      Lophomyrtus bullata (Myrtaceae). GC and NMR analyses of essential oils and
      solvent extracts of L. bullata, L. obcordata and the hybrid L. "ralphii" showed
      several chemotypes, which did not correlate with species. Levels of 1 and 2
      varied from dominant to low/undetectable and the most common chemotype was rich
      in allo-aromadendrene and other sesquiterpenes. The rare natural product E-4
      methyl-1-phenyl-1-penten-3-one 4 was detected for the first time in this genus.
      The non-volatile cytotoxic compound bullataketal 5 co-occurred with bullatenone
      1. An essential oil from the relatively rare bullatenone 1 chemotype showed
      antifungal activity against Candida albicans and Cladosporium resinae, and an oil
      from the 4-methyl-1-phenylpentane-1,3-dione 2 chemotype showed antibacterial
      activity against Bacillus subtilis.

PMID- 18329060
TI  - Direct binding and activation of protein kinase C isoforms by steroid hormones.
AB  - The non-genomic action of steroid hormones regulates a wide variety of cellular
      responses including regulation of ion transport, cell proliferation, migration,
      death and differentiation. In order to achieve such plethora of effects steroid
      hormones utilize nearly all known signal transduction pathways. One of the key
      signalling molecules regulating the non-genomic action of steroid hormones is
      protein kinase C (PKC). It is thought that rapid action of steroids hormones
      results from the activation of plasma membrane receptors; however, their
      molecular identity remains elusive. In recent years, an increasing number of
      studies have pointed at the selective binding and activation of specific PKC
      isoforms by steroid hormones. This has led to the hypothesis that PKC could act
      as a receptor as well as a transducer of the non-genomic effects of these
      hormones. In this review we summarize the current knowledge of the direct binding
      and activation of PKC by steroid hormones.

PMID- 18329061
TI  - Development of a highly sensitive and selective UPLC/MS/MS method for the
      simultaneous determination of testosterone and 5alpha-dihydrotestosterone in
      human serum to support testosterone replacement therapy for hypogonadism.
AB  - A highly sensitive and selective quantitative method to accurately determine
      testosterone (Te) and 5alpha-dihydrotestosterone (DHT) in human serum is crucial
      to the success of Te replacement therapy for hypogonadism. To this end we have
      developed and validated a semi-automated and relatively high-throughput method in
      a 96-well plate format using ultra-performance liquid chromatography coupled with
      tandem mass spectrometry (UPLC/MS/MS) for the simultaneous determination of Te
      and DHT in human serum. Te and DHT along with the internal standards [(2)H(3)]-Te
      and [(2)H(3)]-DHT were extracted from 300 microL of human serum by liquid-liquid
      extraction using methyl tertiary-butyl ether (MTBE), followed by derivatization
      with 2,3-pyridinedicarboxylic anhydride and solid-phase extraction for sample
      clean up. A novel chemical derivatization approach using 2,3-pyridinedicarboxylic
      anhydride was employed to achieve the MS sensitivity and selectivity required for
      DHT. Baseline separation of Te and DHT derivatives from endogenous steroid
      derivatives was achieved using UPLC technology on a C18 stationary-phase column
      with 1.7 microm particle size. The validity of using double charcoal-stripped
      female human serum as surrogate matrix for preparation of calibration standards
      was demonstrated through standard addition experiments. The method was validated
      over the concentration ranges of 0.2-40 ng/mL for Te and 0.01-2 ng/mL for DHT.
      The validation and study sample analysis results show that the method is rugged,
      precise, accurate, and well suited to support pharmacokinetic studies where
      approximately 300 samples can be extracted and analyzed in 1 day.

PMID- 18329062
TI  - Use of epidemiologic data in Integrated Risk Information System (IRIS)
      assessments.
AB  - In human health risk assessment, information from epidemiologic studies is
      typically utilized in the hazard identification step of the risk assessment
      paradigm. However, in the assessment of many chemicals by the Integrated Risk
      Information System (IRIS), epidemiologic data, both observational and
      experimental, have also been used in the derivation of toxicological risk
      estimates (i.e., reference doses [RfD], reference concentrations [RfC], oral
      cancer slope factors [CSF] and inhalation unit risks [IUR]). Of the 545 health
      assessments posted on the IRIS database as of June 2007, 44 assessments derived
      non-cancer or cancer risk estimates based on human data. RfD and RfC calculations
      were based on a spectrum of endpoints from changes in enzyme activity to specific
      neurological or dermal effects. There are 12 assessments with IURs based on human
      data, two assessments that extrapolated human inhalation data to derive CSFs and
      one that used human data to directly derive a CSF. Lung or respiratory cancer is
      the most common endpoint for cancer assessments based on human data. To date,
      only one chemical, benzene, has utilized human data for derivation of all three
      quantitative risk estimates (i.e., RfC, RfD, and dose-response modeling for
      cancer assessment). Through examples from the IRIS database, this paper will
      demonstrate how epidemiologic data have been used in IRIS assessments for both
      adding to the body of evidence in the hazard identification process and in the
      quantification of risk estimates in the dose-response component of the risk
      assessment paradigm.

PMID- 18329063
TI  - Full genomic analysis of human rotavirus strain TB-Chen isolated in China.
AB  - A G2P[4]/NSP4[A] rotavirus strain TB-Chen was isolated from a 2-year-old patient
      hospitalized with acute gastroenteritis in Kunming, China. The strain TB-Chen was
      demonstrated having group A-specific antigenicity, a "short" (subgroup II)
      electropherotype. To investigate its overall genomic relatedness and to determine
      which group it belonged, the complete genome of strain TB-Chen was determined.
      Genomic comparison based on amino acid sequence identity and phylogenetic
      analysis revealed that all 11 gene segments of strain TB-Chen were highly
      identical (>91.80%) with the representative G2P[4]/NSP4[A] human strains DS-1,
      S2, NR1 and IS2, suggesting that this rotavirus strain was derived from human
      host. Besides, almost all the available representative rotavirus gene segments
      among group A were analyzed and identified within 15 G-types, 28 P-types, and 6
      NSP4 genotypes. This is the first report of group A rotavirus genomic analyses in
      China and the findings have important implications for rotavirus vaccine
      development.

PMID- 18329064
TI  - Rose spring dwarf-associated virus has RNA structural and gene-expression
      features like those of Barley yellow dwarf virus.
AB  - We determined the complete nucleotide sequence of the Rose spring dwarf
      associated virus (RSDaV) genomic RNA (GenBank accession no. EU024678) and
      compared its predicted RNA structural characteristics affecting gene expression.
      A cDNA library was derived from RSDaV double-stranded RNAs (dsRNAs) purified from
      infected tissue. Nucleotide sequence analysis of the cloned cDNAs, plus for
      clones generated by 5'- and 3'-RACE showed the RSDaV genomic RNA to be 5808
      nucleotides. The genomic RNA contains five major open reading frames (ORFs), and
      three small ORFs in the 3'-terminal 800 nucleotides, typical for viruses of genus
      Luteovirus in the family Luteoviridae. Northern blot hybridization analysis
      revealed the genomic RNA and two prominent subgenomic RNAs of approximately 3 kb
      and 1 kb. Putative 5' ends of the sgRNAs were predicted by identification of
      conserved sequences and secondary structures which resembled the Barley yellow
      dwarf virus (BYDV) genomic RNA 5' end and subgenomic RNA promoter sequences.
      Secondary structures of the BYDV-like ribosomal frameshift elements and cap
      independent translation elements, including long-distance base pairing spanning
      four kb were identified. These contain similarities but also informative
      differences with the BYDV structures, including a strikingly different structure
      predicted for the 3' cap-independent translation element. These analyses of the
      RSDaV genomic RNA show more complexity for the RNA structural elements for
      members of the Luteoviridae.

PMID- 18329065
TI  - The role of early visual cortex in visual short-term memory and visual attention.
AB  - We measured cortical activity with functional magnetic resonance imaging to probe
      the involvement of early visual cortex in visual short-term memory and visual
      attention. In four experimental tasks, human subjects viewed two visual stimuli
      separated by a variable delay period. The tasks placed differential demands on
      short-term memory and attention, but the stimuli were visually identical until
      after the delay period. Early visual cortex exhibited sustained responses
      throughout the delay when subjects performed attention-demanding tasks, but delay
      period activity was not distinguishable from zero when subjects performed a task
      that required short-term memory. This dissociation reveals different
      computational mechanisms underlying the two processes.

PMID- 18329066
TI  - Binocular switch suppression: a new method for persistently rendering the visible
      'invisible'.
AB  - Rendering the usually visible 'invisible' has long been a popular experimental
      manipulation. With one notable exception, 'continuous flash suppression'
      [Tsuchiya, N., & Koch, C. (2005). Continuous flash suppression reduces negative
      afterimages. Nature Neuroscience, 8, 1096-1101], existing methods of achieving
      this goal suffer from being either unable to suppress stimuli from awareness for
      prolonged periods, from being unable to reliably suppress stimuli at specific
      epochs, or from a combination of both of these limitations. Here we report a new
      method, binocular switch suppression (BSS), which overcomes these restrictions.
      We establish that BSS is novel as it taps a different causal mechanism to the
      only similar pre-existing method. We also establish that BSS is superior to pre
      existing methods both in terms of the depth and duration of perceptual
      suppression achieved. BSS should therefore prove to be a useful tool for the
      large number of researchers interested in exploring the neural correlates and
      functional consequences of conscious visual awareness.

PMID- 18329067
TI  - Modulation of antioxidant defences in digestive gland of Perna viridis (L.), on
      mercury exposures.
AB  - Sub-lethal effects of mercury exposure (110th of LC(50), i.e. 0.045 mg l(-1)) for
      5, 10 and 15 d was investigated on oxidative stress parameters and antioxidant
      defences in digestive gland of Perna viridis. In addition to this an in vitro
      effect of mercury single and supplemented with reduced glutathione on lipid
      peroxidation was studied. Increased lipid peroxidation (during first 10 days and
      also during in vitro exposures), protein carbonyl and hydrogen peroxides (from
      5th till last day of exposure) indicate the resultant oxidative stress in the
      mercury exposed specimen. DNA damage (F-value) response although less distinct on
      5th and 15th d, its low values on 10th d and significant correlation with
      hydrogen peroxide suggests the toxic role of free radicals towards DNA integrity.
      Superoxide dismutase, which remains low initially (5th d) and increases later
      suggests its immediate response against superoxide radical. Higher activities of
      catalase, glutathione peroxidase and glutathione reductase on 15th d and
      glutathione-S-tranferase from 10th d onwards suggests the adaptive behaviour of
      the tissue against oxyradicals. Increasing levels of non-enzymatic antioxidant
      molecules, such as reduced glutathione and ascorbic acid indicated its
      involvement in counteracting oxidative damage. Further role of reduced
      glutathione in reducing Hg toxicity is evident in in vitro experiments where
      lipid peroxidation remains low in mercury concentrations supplemented with
      reduced glutathione. The elevated levels of metallothionein from 5th to 10th d
      suggest involvement of this protein in detoxification of reactive oxygen species
      and toxic metal. The above results suggest that both enzymatic and non-enzymatic
      antioxidants play an important role in protecting cell against Hg toxicity, which
      can be used as a biomarker of metal contamination in aquatic environment.

PMID- 18329068
TI  - Cytotoxicity of municipal solid waste incinerator ash wastes toward mammalian
      kidney cell lines.
AB  - In this study, three municipal solid waste incinerator (MSWI) ash wastes-bottom
      ash, scrubber residue, and baghouse ash-were extracted using a toxicity
      characteristic leaching procedure (TCLP) extractant. These so-called final TCLP
      extracts were applied to African green monkey kidney cells (Vero), baby hamster
      kidney cells (BHK-21), and pig kidney cells (PK-15), multi-well absorption reader
      analysis was performed to test how the cytotoxicity of the incineration ashes
      would affect the digestive systems of animals. Ion-coupled plasma analyses
      indicated that the baghouse ash extract possessed the highest pH and heavy metal
      concentration, its cytotoxicity was also the highest. In contrast, the bottom ash
      and the scrubber residue exhibited very low cytotoxicities. The cytotoxicities of
      mixtures of baghouse ash and scrubber residue toward the three tested cell lines
      increased as the relative ratio of the baghouse ash increased, especially for the
      Vero cells. The slight cytotoxicity of the scrubber residue arose mainly from the
      presence of Cr species, whereas the high cytotoxicity of the baghouse ash
      resulted from its high content of heavy metals and alkali ions. In addition, it
      appears that the dissolved total organic carbon content of these ash wastes can
      reduce the cytotoxicity of ash wastes that collect in animal cells.

PMID- 18329069
TI  - Occurrence and distribution of hexachlorocyclohexane isomers in vegetation
      samples from a contaminated area.
AB  - The occurrence and distribution of four major hexachlorocyclohexane (HCH) isomers
      (alpha-, beta-, gamma- and delta-) were studied in vegetation samples of a highly
      contaminated area close to a small-scale industrial belt in Lucknow (North
      India). Eight species of plants were collected at different points of the
      contaminated area and different parts of the plants were separated in order to
      study the difference in uptake and accumulation. The samples were extracted by
      matrix solid-phase dispersion (MSPD) extraction and finally determined by a gas
      chromatograph equipped with (63)Ni electron capture detector (ECD). HCH isomers
      were present in almost all samples and the concentration of total HCH in the
      plant sample analyzed varied between 13 and 44 mg kg(-1), being the main isomer
      of beta-HCH (8-22 mg kg(-1)). Lindane (gamma-HCH) was present in all samples (1-9
      mg kg(-1)). Solanum torvum Sw., and Erianthus munja shows the highest and lowest
      capacity for accumulation of HCH, respectively with a significant difference at
      p<0.01 level. The highest concentration of HCH residue in root samples indicates
      the most likely mechanism of HCH accumulation in these plants was sorption of
      soil HCH on roots. Solanum torvum Sw., and Withania somnifera (L.) Dunal could
      accumulate considerable levels of HCH isomers (44 and 34 mg kg(-1),
      respectively). The results reflect the importance of plants in monitoring
      purposes and their potential for phytoremediation of HCH contaminated soils.

PMID- 18329070
TI  - Decomposition of paper wastes in presence of ceramics and cement raw material.
AB  - Paper recycling is an environmental important activity that is carried out in all
      the countries, but during the recycling process a paper waste is produced.
      Generally these wastes are placed in landfill sites but it is possible to profit
      it as secondary fuel and raw material in manufacture furnaces. In this work the
      combustion of the waste papers with cement and ceramic raw material has been
      studied with the objective to analyse the interaction of these substances with
      the emitted pollutants like PAHs and PCDD/Fs. The results of the study show that
      the presence of inorganic material produces an increment in the lighter PAH
      emission but chlorinated compounds are not affected. The PCDD/F emission level
      found in the combustion of this waste is quite low compared with other wastes
      subjected to similar conditions.

PMID- 18329071
TI  - Use of nonsteroidal anti-inflammatory drugs after radical retropubic
      prostatectomy: a prospective, randomized trial.
AB  - OBJECTIVES: To assess the efficacy and safety of nonsteroidal anti-inflammatory
      drugs (NSAIDs) administered after radical retropubic prostatectomy (RRP).
      METHODS: One hundred patients undergoing open RRP by one surgeon were divided
      randomly and prospectively into two groups of 50 patients, each receiving
      systematically either an NSAID (lornoxicam) or paracetamol for postoperative
      analgesia. Opiates were administered if needed for breakthrough pain. Parameters
      potentially correlated with postoperative bleeding, such as preoperative and
      postoperative hemoglobin (Hb) differences, estimated blood loss, number of
      transfusions, and drain output were recorded. Furthermore, the degree of pain was
      assessed daily with a visual analogue scale score until discharge from hospital.
      RESULTS: After procedures with similar estimated blood loss, postoperative
      bleeding was not more in the NSAIDs group, as evidenced by similar transfusion
      rates (P <or=1), similar postoperative Hb values (P >0.05), and Hb drop after the
      procedure. No patient required re-exploration for bleeding; drain output when
      elevated was never attributed to postoperative bleeding. Pain control as
      evaluated by the visual analogue scale pain score was adequate with the use of
      NSAIDs and not statistically different from the non-NSAIDs group during
      postoperative days 1 and 4 and onward. Pain control with lornoxicam was even
      better on postoperative days 2 and 3 (P <or=0.05). CONCLUSIONS: Nonsteroidal anti
      inflammatory drugs administered after open RRP are safe and effective. They do
      not increase the risk of bleeding and offer improved analgesia.

PMID- 18329072
TI  - Adult wilms tumor in the renal pelvis: case report with review of the literature.
AB  - An 84-year-old man was referred to our hospital with gross hematuria. Abdominal
      computed tomography demonstrated a well-circumscribed enhanced mass in the right
      pelviureteral junction. Retroperitoneoscopic nephroureterectomy was performed
      because of a clinical diagnosis of renal pelvic carcinoma. Pathologic examination
      led to a final diagnosis of an adult Wilms tumor arising from the renal pelvis.
      This is the first report of a Wilms tumor in the renal pelvis of an adult
      patient.

PMID- 18329074
TI  - Re: "Progression of renal tumors after laparoscopic radiofrequency ablation.
      Urology 68: 968-971, 2006".

PMID- 18329075
TI  - Solitary liver metastasis of chromophobe renal cell carcinoma 20 years after
      nephrectomy treated by hepatic resection.
AB  - A small proportion of patients with metastatic renal cell carcinoma have operable
      liver metastases, as there is often multiple dissemination within the liver and
      to other organs. We present a case of a solitary liver metastasis found
      incidentally 20 years after radical nephrectomy for a chromophobe renal cell
      carcinoma. The patient underwent a liver resection with tumor-free margins and
      recovered uneventfully. Time will tell if this was oncologically successful.

PMID- 18329076
TI  - Evaluation of efficacy of novel optically activated digital endoscope protection
      system against laser energy damage.
AB  - OBJECTIVES: To evaluate the reliability and efficacy of a novel endoscope
      protection system (EPS) against direct laser energy damage. METHODS: We performed
      in vitro evaluations of a novel EPS prototype that uses optical feedback from the
      digital sensor of the DUR-D ureteroscope to terminate the laser energy on
      retraction of the laser fiber into the ureteroscope. We evaluated various speeds
      of retraction (0.5, 2.0, and 5.0 cm/s) in normal saline and various
      concentrations of indigo carmine and human blood. We also evaluated the
      protrusion distance at which shutdown occurred with the laser fiber cladding
      cleaved at 0, 3, and 5 mm from the end of the fiber. Twenty trials of each
      condition were performed. RESULTS: In normal saline and blood dilutions of up to
      10 g/L, the EPS worked with 100% efficiency for all trials. For blood dilutions
      of 10 g/L or greater and indigo carmine concentrations of 0.16 g/L or greater,
      the reliability of the EPS deteriorated. Lasers stripped of 0, 3, and 5 mm of
      cladding initiated shutdown at 2.9 +/- 0.13, 5.1 +/- 0.09, and 8.2 +/- 0.15 mm
      from the ureteroscope distal end, respectively (P <0.01). A single DUR-D
      ureteroscope was used for all trials and remained completely intact through 120
      retractions of the active laser fiber into the channel. CONCLUSIONS: In this
      evaluation, the novel EPS was highly effective and reliable. When using indigo
      carmine or high-density blood concentrations, the efficacy of the EPS was
      compromised. The EPS should be used to complement standard safe laser technique
      rather than to replace it.

PMID- 18329077
TI  - Costs of interstitial cystitis in a managed care population.
AB  - OBJECTIVES: To assess the direct medical costs, medication, and procedure use
      associated with interstitial cystitis (IC) in women in the Kaiser Permanente
      Northwest (KPNW) managed care population. METHODS: The KPNW electronic medical
      record was used to identify women diagnosed with IC (n = 239). Each of these
      patients was matched with three controls according to age and duration in the
      health plan. Health plan cost accounting data were used to determine the
      inpatient, outpatient, and pharmacy costs for 1998 to 2003. An analysis of the
      prescription medication use and cystoscopic and urodynamic procedures commonly
      associated with IC was also performed. To evaluate for co-morbidities, an
      automated risk-adjustment model linked to 28 chronic medical conditions was
      applied to the administrative data sets from both groups. RESULTS: The mean
      duration from the date of IC diagnosis to the end of the study period was 36.6
      months (range 1.4 to 60). The mean yearly costs were 2.4-fold greater for the
      patients than for the controls ($7100 versus $2994), and the median yearly costs
      were 3.8-fold greater ($5000 versus $1304). These cost differences were
      predominantly due to outpatient and pharmacy expenses. Medication and procedure
      use were significantly greater for the patients than for the controls. These
      findings were consistent across risk-adjustment model categories, which suggest
      that the observed cost differences are IC specific. CONCLUSIONS: The direct per
      person costs of IC are high, with average yearly costs approximately $4000
      greater than for the age-matched controls. This cost differential is an
      underestimate, because the costs preceding the diagnosis, the use of alternative
      therapies, indirect costs, and the costs of those with IC that is not diagnosed
      were not included.

PMID- 18329078
TI  - Potential of magnetic resonance spectroscopic imaging in predicting absence of
      prostate cancer in men with serum prostate-specific antigen between 4 and 10
      ng/ml: a follow-up study.
AB  - OBJECTIVES: Screening for prostate cancer using serum prostate-specific antigen
      (PSA) determination has a positive predictive value of only 30% to 42% for a PSA
      level between 4 and 10 ng/mL. Magnetic resonance spectroscopic imaging (MRSI),
      which identifies cancer on the basis of changes in cellular metabolite levels,
      might be able to identify patients with noncancerous PSA elevation and help avoid
      unnecessary biopsies. We tested this hypothesis by evaluating the incidence of
      prostate cancer in men with a PSA level of 4 to 10 ng/mL and a negative MRSI
      study. METHODS: A total of 155 men underwent a three-dimensional proton MRSI of
      the prostate before transrectal ultrasound-guided biopsy for clinical
      indications. MRSI was performed using an endorectal coil on a 1.5-T magnetic
      resonance scanner. Patients with no voxels positive for malignancy underwent
      standard sextant biopsy, and additional MRSI-targeted biopsies were obtained in
      men with suspicious or malignant voxels. Patients with a biopsy negative for
      cancer underwent repeat serum PSA estimation every 6 months for a minimum of 18
      months. RESULTS: Of the 155 men, 36 (mean PSA level of 6.47 ng/mL, range 4.25 to
      9.9) had no malignant voxels on MRSI. None of them were positive for cancer on
      biopsy. Of these 36 men, 26 completed at least 18 months (mean 26.9, range 18 to
      44) of follow-up. Four patients required repeat biopsies and one, with a
      persistently elevated PSA level was diagnosed with prostate cancer 29 months
      after the initial MRSI. CONCLUSIONS: The results of our study have shown that
      prostate biopsy can be deferred in patients with an increased serum PSA of 4 to
      10 ng/mL if their MRSI does not show any malignant voxels.

PMID- 18329079
TI  - Rare renal pseudotumor associated with chronic glomerulonephritis mimicking renal
      cell carcinoma.
AB  - We describe a unique case of chronic glomerulonephritis that simulated a renal
      neoplasm observed on abnormal imaging. Histologic examination of the resected
      specimen supported the assumption that the observed mass lesion resulted from
      regional sparing in the development of chronic glomerulonephritis. We believe
      this case is the first to show the etiology of pseudotumor as an extremely
      uncommon manifestation of chronic glomerulonephritis by histologic examination.

PMID- 18329080
TI  - Complications of open radical retropubic prostatectomy in potential candidates
      for active monitoring.
AB  - OBJECTIVES: With the widespread use of prostate-specific antigen (PSA)-based
      screening, there is now concern about the overdiagnosis and overtreatment of men
      with low-risk prostate cancer (PCa). One of the most difficult aspects of PCa
      management is a balance of the often-competing goals of cancer control with
      functional outcomes and quality of life. To address this issue, we examined the
      potency, continence and overall complication rates associated with radical
      prostatectomy (RP), specifically in potential candidates for active monitoring.
      METHODS: From a large RP database, we compared potency, continence, and
      complication rates among men meeting one of the following active monitoring
      criteria from the literature: clinically localized, Gleason score of 7 or less,
      and no significant comorbidities; T1b-T2b NOMO, Gleason score of 7 or less, and
      PSA of 15 ng/mL or less; and T1c PCa. RESULTS: There were 3458, 3533, and 2338
      men who met the above criteria, respectively. After 18 months of follow-up,
      potency was preserved in 70% to 74%. At least 93% of patients were continent, and
      the rate of surgical complications ranged from 5% to 7%. Increasing age was
      significantly associated with a greater risk of all complications. CONCLUSIONS:
      Men with newly diagnosed low-risk PCa must carefully weigh the risks and benefits
      of treatment. In young men with low-risk PCa, RP was associated with a relatively
      low complication rate and good long-term functional outcomes. However, with
      increasing age, RP was associated with significantly higher complication rates.
      These results can be used to help guide management decisions for men with low
      risk disease.

PMID- 18329081
TI  - Acute epididymitis in children: the role of radiologic studies.
AB  - OBJECTIVES: Assessment of the role of radiologic studies in the detection of
      significant urologic anomalies in boys with acute epididymitis. METHODS:
      Retrospective chart reviews of patients with a diagnosis of acute epididymitis
      over a period of 15 years (January 1989 to December 2003). Patients presented
      with an acute scrotum and documented ipsilateral testicular/epididymal hyperemia
      on Doppler ultrasound plus any 2 of the following criteria: (1) high-grade fever
      (higher than 38.5 degrees C), (2) peripheral leukocytosis, (3) pyuria greater
      than 10 pus cells per high-power field, and (4) positive urine culture. The
      results of upper tract imaging and voiding cystourethrogram (VCUG) were reviewed
      for any anatomic abnormality. RESULTS: Sixteen patients were included in this
      review, age range 3 weeks to 16 years (median 10.5 years). Fifteen of 16 patients
      had upper tract imaging (13 renal ultrasound and 2 intravenous pyelogram [IVP]).
      All upper tract imaging studies were normal. VCUG was performed in 13 of 16
      patients, and was normal in 12 of 13 patients. One patient had reflux to right
      seminal vesicle, which resolved spontaneously on a follow-up study. The follow-up
      period ranged from 1 month to 11 years (median 2 months). None of the patients
      had recurrent epididymitis, except the individual who had reflux to seminal
      vesicle. CONCLUSIONS: A full radiologic workup to include a renal ultrasound and
      VCUG should be obtained in children with acute epididymitis and a positive urine
      culture, or recurrent epididymitis. In a child with acute epididymitis and
      negative urine culture, urinary tract ultrasound is adequate. Because VCUG is of
      low yield in this population, its routine use should be questioned.

PMID- 18329082
TI  - Conditional survival in ovarian cancer: results from the SEER dataset 1988-2001.
AB  - OBJECTIVES: Survival statistics for patients with ovarian cancer are typically
      reported in terms of survival from time of diagnosis. For patients who have
      survived a period of time since diagnosis, however, conditional survival (CS) is
      a more clinically relevant measure, as it accounts for the changes in risk over
      time. The purpose of this study was to estimate CS for ovarian cancer patients
      through analysis of large-scale cancer registry data. METHODS: Ovarian cancer
      cases were extracted from the Surveillance, Epidemiology, and End Results (SEER
      17) database from the National Cancer Institute (NCI) for patients diagnosed
      between 1988-2001. Five-year relative CS calculations were performed with
      stratification by age, race, stage, histology, and grade for patients who had
      already survived up to 5 years from diagnosis. RESULTS: The 5-year overall
      relative CS improved over time for up to 5 years after diagnosis for ovarian
      cancer patients. The largest gains in CS over time were seen for patients with
      advanced stage disease, poor grade, and serous and undifferentiated epithelioid
      histologies. For patients with stage IV disease, 5-year CS more than tripled over
      the first 5 years of surveillance (17%-56%). Among histological types, patients
      with undifferentiated epithelioid histology saw 5-year CS rise from 29% at
      diagnosis to 84% after 5 years. CONCLUSIONS: Prognosis improves over time for
      almost all groups of ovarian cancer patients. For ovarian cancer survivors, CS
      provides a more relevant measure of prognosis than conventional survival
      estimates that are made at the time of diagnosis.

PMID- 18329083
TI  - Prognostic value of serum CA 125 bi-exponential decrease during first line
      paclitaxel/platinum chemotherapy: a French multicentric study.
AB  - BACKGROUND: CA 125 assays enable treatment-response monitoring in ovarian cancer.
      METHODS: A multicentric study of CA 125 kinetics under paclitaxel/platinum-based
      chemotherapy was performed in 130 stage IIc-IV patients. CA 125 half-life and
      nadir concentration were compared to patient outcome. Some patients (n=38, 29.2%)
      presented a CA 125 bi-exponential decrease and its clinical implication was
      studied. Survival analyses for disease-free survival (DFS) and overall survival
      (OS) used univariate (Kaplan-Meier) and multivariate (Cox model). RESULTS: During
      a median follow-up time of 29 months (range 5-106 months), 111 patients (85%)
      relapsed and 94 (72%) died from ovarian cancer. Patients were split into 4 groups
      according to their pattern of CA 125 decrease: non-assessable half-life because
      of a low pre-chemotherapy CA 125 level (n=38), half-life < or = 14 days and mono
      exponential CA 125 decay (n=18), half-life < or = 14 days and bi-exponential CA
      125 decay (n=21), and half-life > 14 days (n=53). In Cox models, nadir
      concentration, residual tumour volume and number of chemotherapy courses were
      found to be independent prognostic factors for DFS and OS. The group
      classification was found to be an independent prognostic factor only for DFS.
      However, when nadir was not introduced in the models, the CA 125 kinetics groups
      were the most important prognostic factor for OS. CONCLUSION: Characteristics of
      CA 125 kinetics during first line paclitaxel/platinum chemotherapy have a strong
      and independent prognostic value. A CA 125 bi-exponential decrease is an
      indicator of bad prognosis.

PMID- 18329084
TI  - A novel indole ethyl isothiocyanate (7Me-IEITC) with anti-proliferative and pro
      apoptotic effects on platinum-resistant human ovarian cancer cells.
AB  - OBJECTIVE: A novel indole ethyl isothiocyanate derivative (7Me-IEITC) was defined
      as a potent growth-suppressing agent to cell lines derived from ovarian cancers.
      Key mechanisms of the cellular response in vitro were studied and suggest a
      potential of 7Me-IEITC as a therapeutic drug. METHODS: The viability of ovarian
      cancer cell lines (SKOV-3, OVCAR-3) in comparison to pancreatic and prostate
      cancer cell lines, primary fibroblast and immortalized trophoblasts after
      treatment with 7Me-IEITC was analyzed. Morphological and apoptotic responses of
      SKOV-3 were studied by fluorescence microscopy (DAPI staining, TUNEL assay). SKOV
      3 proliferation was estimated by a standardized BrdU incorporation assay. The
      phosphorylation of MAP-Kinases, pro-survival factors and the activation of
      caspases and PARP-1 were analyzed by western blotting. Changes of the
      mitochondrial transmembrane-potential and in cell-cycle progression were studied
      by FACS analysis. MAP-Kinase and caspase inhibitors were employed in cytotoxicity
      studies. RESULTS: 7Me-IEITC selectively reduced the viability of SKOV-3, OVCAR-3,
      BXPC-3 and PC-3 cells (IC(50) values < or = 5 microM), while the viability of
      fibroblasts or trophoblasts remained un-affected at concentrations below 20
      microM. 7Me-IEITC treatment down-regulated pro-survival kinases and transcription
      factors (STAT-3, IKKalpha and NF-kappaB), caused rapid loss of the mitochondrial
      transmembrane-potential and inactivation of PARP-1 along with activation of
      caspases. The use of p38 MAP-Kinase-and caspase inhibitors suppressed the
      cytotoxicity of the drug. 7Me-IEITC acted as an anti-proliferative agent and
      arrested the cell-cycle progression of SKOV-3 in G2/M phase. CONCLUSION: 7Me
      IEITC is a potent and growth-suppressing agent to cell lines derived from ovarian
      cancers by causing deactivation of survival signals, apoptosis, and cell-cycle
      arrest.

PMID- 18329085
TI  - Bupropion differentially impacts acquisition of methamphetamine self
      administration and sucrose-maintained behavior.
AB  - Bupropion reduces the subjective effects and cue-induced craving for
      methamphetamine in humans. Given these effects of bupropion on methamphetamine in
      humans and its widespread clinical use, a preclinical model of drug-taking was
      used to determine if pretreatment with bupropion would alter the acquisition of
      methamphetamine self-administration. During acquisition, rats were given saline
      or bupropion (30 or 60 mg/kg, IP) 5 min before a 60-min session. For the first 8
      days, each response on the active lever produced an infusion of methamphetamine
      (0.025 mg/kg). Responding on the inactive lever had no programmed consequence.
      This FR1 schedule was then increased to an FR3 for 4 more days. In a parallel
      study, the identical procedures were used to test the impact of bupropion on
      sucrose-maintained responding. Bupropion pretreatment decreased the number of
      methamphetamine infusions and sucrose deliveries earned on an FR1 and FR3.
      However, bupropion pretreatment only delayed discrimination between the active
      and inactive levers in the methamphetamine self-administration rats.
      Discrimination between active and inactive levers was acquired in all groups in
      the sucrose experiment regardless of pretreatment condition. Combined, these
      results suggest that bupropion has a more general effect within the
      appetitive/reward system of the brain rather than having complete specificity for
      methamphetamine.

PMID- 18329086
TI  - Effects of acute and repeated administration of caffeine on temporal discounting
      in rats.
AB  - Delay to presentation is one variable that can weaken the reinforcing efficacy of
      an outcome in a choice situation and drugs have been shown to modify such
      choices. A growing body of literature has examined effects of stimulant drugs on
      temporal (delay) discounting, but effects of caffeine, the most widely used
      stimulant in the world, have not previously been assessed. In the present
      experiment, effects of caffeine (administered acutely and repeatedly) on temporal
      discounting were analyzed. Male Sprague-Dawley rats (n=7) chose between a single
      food pellet delivered immediately after a lever press and three food pellets
      delivered after a delay. The delay to the three pellets increased within each
      session, from 0 to 16 s. High doses of caffeine increased large-reinforcer choice
      relative to control conditions. With repeated caffeine exposure, percent choice
      for the large reinforcer decreased relative to acute administration, but was
      still greater than pre-drug baseline. Following withdrawal of drug
      administration, choice returned to levels seen during pre-drug baseline.
      Reintroduction of caffeine increased the percent choice for a larger, delayed
      reinforcer to near acute levels. The results from the present study are
      consistent with previous research in which stimulant drugs have decreased
      temporal (delay) discounting.

PMID- 18329087
TI  - Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside
      pathogenic mechanisms.
AB  - Until quite recently, the pathogenesis of atopic dermatitis (AD) has been
      attributed to primary abnormalities of the immune system. Intensive study
      revealed the key roles played by T(H)1/T(H)2 cell dysregulation, IgE production,
      mast cell hyperactivity, and dendritic cell signaling in the evolution of the
      chronic, pruritic, inflammatory dermatosis that characterizes AD. Accordingly,
      current therapy has been largely directed toward ameliorating T(H)2-mediated
      inflammation and pruritus. In this review we will assess emerging evidence that
      inflammation in AD results from inherited and acquired insults to the barrier and
      the therapeutic implications of this paradigm.

PMID- 18329088
TI  - Protective role of nuclear factor of activated T cells 2 in CD8+ long-lived
      memory T cells in an allergy model.
AB  - BACKGROUND: The transcriptional regulation of cytokines released and controlled
      by memory T cells is not well understood. Defective IFN-gamma production in
      allergic asthma correlates in human beings with the risk of wheezing in
      childhood. OBJECTIVE: To understand the role of the transcription factor nuclear
      factor of activated T cells 2 (NFATc2) in memory and effector T cells in the
      airways in experimental allergic asthma. METHODS: We used murine models of
      allergic asthma and adoptive cell transfer of fluorescence-activated sorted cells
      in a disease model. RESULTS: Mice lacking NFATc2 developed an increase in
      airwayhyperresponsiveness (AHR), remodeling, and serum IgE levelson ovalbumin
      sensitization. This phenotype was associated withCD81CD1222 T cells deficient in
      IFN-g production in theairways. The origin of this phenotype in NFATc2(2/2) mice
      wasrelated to an expanded population of lung CD81CD1221(IL-2Rb chain) CD127hi (IL
      7 receptor [R] a chain1) long-livedmemory cells. Adoptive transfer of ovalbumin
      specific CD81NFATc2(2/2) T cells enhanced the AHR generated byNFATc2(2/2) CD41 T
      cells in immunodeficient mice, increasedIL-17, and reduced IFN-g production in
      the reconstituted mice. Depletion of the memory CD81CD1221IL-7Rhigh T
      cellpopulation corrected the defect in IFN-g production by lungNFATc2(2/2)
      CD81CD1222 cells and abrogated the increasedAHR observed in NFATc2(2/2) CD81 T
      cell-reconstituted micewith a severe combined immunodeficiency disorder.
      CONCLUSION: Taken together, our results suggest that NFATc2 expression in long
      lived memory CD8+ T cells controls IL-2 and IFN-gamma production in lung CD8+ T
      cells, which then limits TH17 and TH2 development in the airways during allergen
      challenge.

PMID- 18329089
TI  - Are the associations between diet and C-reactive protein independent of obesity?
AB  - OBJECTIVES: To determine the relative magnitude of the effect of dietary factors
      on circulating C-reactive protein (CRP) levels, controlling for BMI. METHODS:
      1808 men and 2269 women attended the 1994/95 follow-up survey from the Busselton
      Health Study, Australia. A composite diet score was derived from a short
      questionnaire. Height and weight were measured. RESULTS: After controlling for
      BMI, CRP levels were associated with red meat intake (males only, p=0.001), fruit
      intake (males p<0.0001, females p=0.029), potato intake (males p=0.008, females
      p=0.029), using wholemeal bread (males p=0.014, females p=0.018), using
      polyunsaturated fats as a spread and in cooking (females only, p=0.005), and
      rarely or never adding salt to food (males p=0.012, females p=0.004). The overall
      diet score was significantly (negatively) related to CRP in males (p<0.0001) and
      females (p<0.0001). The relative decrease in CRP from a moderately healthy diet,
      compared to an unhealthy diet was 37% in men and 24% in women. This was
      comparable to a difference in BMI of at least 3 kg/m(2) (or a difference in
      weight of approximately 9 kg for a person of average height). CONCLUSION: A
      healthy diet and lower weight have independent beneficial effects of similar
      magnitude on CRP levels.

PMID- 18329090
TI  - Social capital, political trust and experience of cannabis smoking: a population
      based study in southern Sweden.
AB  - OBJECTIVE: To investigate whether political mistrust in the Riksdag (the national
      parliament in Sweden) is an independent characteristic of cannabis smokers, or
      whether it reflects low confidence in people in general, and therefore low social
      capital. METHOD: The 2004 public health survey in Skane is a cross-sectional
      postal questionnaire study answered by 27,757 respondents aged 18-80 with a 59%
      response rate providing data on political trust, cannabis smoking, and potential
      confounders. RESULTS: 13.9% of the men and 8.3% of the women had smoked cannabis;
      17.3% of the male and 11.6% of the female respondents reported no trust at all in
      the Riksdag, and another 38.2% and 36.2%, respectively, reported a moderate
      political trust. Young age, high education, unemployment, low generalized trust
      in other people, and lower levels of political trust were associated with
      cannabis smoking, even after multiple adjustments. The groups men with no trust
      at all in the Riksdag, and women with high trust, not particularly high political
      trust and no political trust at all had significantly higher odds ratios of
      cannabis smoking than the very high trust reference category. The results thus
      somewhat differed between men and women. CONCLUSION: Low political trust is
      associated with cannabis smoking, independently of trust in people in general.

PMID- 18329091
TI  - Preventive potential of body mass reduction to lower cardiovascular risk: the
      Italian Progetto CUORE study.
AB  - OBJECTIVE: To estimate effects of weight change on incidence of major
      cardiovascular events in the Italian population-based Progetto CUORE. METHODS:
      Prospective observation in 12 Italian population-based cohorts on etiology of
      cardiovascular disease. Twenty-thousand six-hundred-forty-seven men and women
      aged 35-69 years without previous CVD, examined at baseline between 1984 and 1993
      and followed for median time 8.5 years, with validated first cardiovascular
      events. Standardised anthropometric variables, lifestyle and biochemical risk
      factors for CVD; major cardiovascular events as end-points. RESULTS: Linear
      regression between BMI and major CVD risk factors was combined with Cox
      coefficients from a prediction model of CVD, CHD and stroke using major risk
      factors as dependent variables. Estimated cardiovascular risk reductions with BMI
      lowered by 1 to 3 U were: for men 3.8% to 10.9% for all cardiovascular events,
      4.2% to 12.1% for CHD, and 2.3% to 6.9% for stroke; for women 2.8% to 8.1% for
      all cardiovascular events, 3.4% to 9.8% for CHD, and 2.1% to 6.2% for stroke.
      CONCLUSIONS: Body weight level influences cardiovascular disease risk in the
      Italian population.

PMID- 18329092
TI  - Smoking in a popular German television crime series 1985-2004.
AB  - OBJECTIVE: We aimed to study the prevalence of smoking in a popular German
      television crime series ("A case for two"), which has been internationally
      distributed in 59 countries, over a 20 year period. METHOD: A content analysis of
      five randomly selected episodes per year of one crime series for the period 1985
      to 2004 (100 episodes in total) was conducted. Smoking status of all major and
      minor series characters was assessed. Each episode was coded regarding one or
      more smoking occurrences, defined as active smoking or handling with tobacco
      products by a character. RESULTS: 97% of the episodes portrayed tobacco use with
      a median of 5 occurrences per episode. The series contained 1013 major and minor
      characters; the overall smoking prevalence was 17.1%. A downward trend in smoking
      occurrences and prevalence of major and minor characters who smoke from 1985 was
      followed by an increase in the last decade. CONCLUSION: Tobacco use is frequently
      portrayed in a popular prime-time German crime series, following a U curve over a
      20 year period.

PMID- 18329093
TI  - Speaking with a single cerebral hemisphere: fMRI language organization after
      hemispherectomy in childhood.
AB  - Speech-related fMRI activation was examined in six hemispherectomy patients
      (three left LX, three right RX, four with congenital and two with late-acquired
      hemiplegia) operated in childhood for the relief of drug-resistant epilepsy.
      Although the temporal and sensorimotor pattern of activation was similar to that
      found in neurologically intact control participants, activation in Broca's area
      and its right homolog varied greatly. Involvement of pars triangularis and
      orbitalis was found in the three cases with best outcome (two RX, one LX),
      whereas pars opercularis alone was activated in the two remaining LX patients.
      The results suggest that distinct subregions of Broca's area and their right
      homologs can subserve speech and language, and that this variability may
      determine functional outcome.

PMID- 18329095
TI  - Potential of various drugs to inhibit nucleoside uptake in rat
      syncytiotrophoblast cell line, TR-TBT 18d-1.
AB  - The placenta requires nucleosides as nutrients for fetal growth, so it is
      important to examine potential interactions between placental transports of
      nucleosides and drugs to ensure the safety of pharmacotherapy during pregnancy.
      The purposes of this study are to clarify the uptake mechanisms of nucleosides
      from the maternal side of the syncytiotrophoblast and to investigate the
      inhibitory effect of various drugs on nucleoside uptake, using the rat
      syncytiotrophoblast cell line TR-TBT 18d-1, which shows syncytial-like morphology
      and functional expression of several transporters. Initial uptake of
      [(3)H]uridine or [(3)H]adenosine from the apical side of TR-TBT 18d-1 was
      markedly reduced by an excess of the respective unlabelled compound, and was
      slightly reduced by replacement of Na(+) with N-methyl-d-glucamine, indicating
      that both uptakes were Na(+)-independent. [(3)H]Uridine and [(3)H]adenosine
      uptakes in the absence of Na(+) were significantly and concentration-dependently
      inhibited by both 0.1 microM and 100 microM nitrobenzylthioinosine, suggesting
      the involvement of equilibrative nucleoside transporters (ENTs, SLC29). Kinetic
      analysis of adenosine uptake yielded a K(m) value of approximately 17 microM.
      These results are consistent with the reported uptake characteristics of uridine
      and adenosine by ENT1 and ENT2. The uptakes were significantly reduced by high
      concentrations of several nucleoside drugs, including cytarabine, vidarabine,
      zidovudine, mizoribine, caffeine and amitriptyline, but the effects were small
      within the therapeutic concentration ranges. In summary, our results suggest that
      ENTs are involved in apical uptake of uridine and adenosine in the
      syncytiotrophoblast. However, therapeutic concentrations of the drugs tested in
      this study might have little influence on maternal-to-fetal nucleoside transfer.

PMID- 18329096
TI  - Monoaminergic compensation in the neuropeptide Y deficient mouse brain.
AB  - Neuropeptide Y (NPY) is an important central regulator of food consumption and
      energy expenditure via the hypothalamus. NPY containing neurons have a broad
      central distribution and are often colocalized with norepinephrine (NE). However,
      NPY deficient mice do not exhibit any substantial changes in food consumption,
      body weight or body composition when compared to wild type mice. Since NE and
      serotonin (5HT) are also important regulators of appetite and metabolism, we
      evaluated these systems in NPY deficient mice. Brain sections from NPY deficient
      and wild type mice were labeled with either (3)H-nisoxetine for the NE
      transporter (NET) or (3)H-citalopram for the 5HT transporter (SERT). Tyrosine
      hydroxylase expression was evaluated by radioimmunohistochemistry. Brain
      monoamines and metabolites were evaluated using HPLC. NPY deficient mice
      exhibited a substantial decrease in NET binding in most brain regions examined.
      NET binding was less than 50% of control binding in the cerebral cortex and
      subregions of the thalamus with the greatest decrease seen in the hypothalamus.
      In contrast, more modest and regionally variable changes were observed in the
      SERT binding with decreases in regions such as the accessory olfactory nucleus,
      glomerular layer of the olfactory bulb and the CA1 region of the hippocampus.
      Measurement of NE and 5HT content as well as the primary metabolites revealed
      increased NE turnover and decreased 5HT content in the hypothalamus. Therefore,
      developmental compensation by the NE and 5HT systems may contribute to the
      absence of a body weight phenotype in NPY deficient mice.

PMID- 18329094
TI  - Thrombin.
AB  - Thrombin is a Na+-activated, allosteric serine protease that plays opposing
      functional roles in blood coagulation. Binding of Na+ is the major driving force
      behind the procoagulant, prothrombotic and signaling functions of the enzyme, but
      is dispensable for cleavage of the anticoagulant protein C. The anticoagulant
      function of thrombin is under the allosteric control of the cofactor
      thrombomodulin. Much has been learned on the mechanism of Na+ binding and
      recognition of natural substrates by thrombin. Recent structural advances have
      shed light on the remarkable molecular plasticity of this enzyme and the
      molecular underpinnings of thrombin allostery mediated by binding to exosite I
      and the Na+ site. This review summarizes our current understanding of the
      molecular basis of thrombin function and allosteric regulation. The basic
      information emerging from recent structural, mutagenesis and kinetic
      investigation of this important enzyme is that thrombin exists in three forms,
      E*, E and E:Na+, that interconvert under the influence of ligand binding to
      distinct domains. The transition between the Na+ -free slow from E and the Na+ 
      bound fast form E:Na+ involves the structure of the enzyme as a whole, and so
      does the interconversion between the two Na+ -free forms E* and E. E* is most
      likely an inactive form of thrombin, unable to interact with Na + and substrate.
      The complexity of thrombin function and regulation has gained this enzyme pre
      eminence as the prototypic allosteric serine protease. Thrombin is now looked
      upon as a model system for the quantitative analysis of biologically important
      enzymes.

PMID- 18329097
TI  - Comparison of examination methods used in the evaluation of prepubertal and
      pubertal female genitalia: a descriptive study.
AB  - OBJECTIVE: To compare the effectiveness of three different examination methods in
      their ability to help the examiner detect both acute and non-acute genital
      injuries in prepubertal and pubertal girls suspected of having been sexually
      abused. METHODS: Forty-six prepubertal and 74 pubertal girls, whose ages ranged
      from 4 months to 18 years, were evaluated to determine the relative effectiveness
      of three different examination methods. RESULTS: All the girls had sustained a
      recent genital injury from various causes. The mean time between an injury and
      the first examination was 24h for the prepubertal girls and 27h for the pubertal
      girls. The three "multimethod" examination approaches used were the supine labial
      separation method; the supine labial traction technique; and the prone knee-chest
      position. The supine labial separation method was useful in identifying an injury
      on the external portion of the genitalia in both groups of girls. Injuries within
      the vestibule, on the hymenal surface, or in the fossa navicularis required
      greater separation of the labia. This was accomplished through the use of either
      the supine labial traction technique or the prone knee-chest position. The prone
      knee-chest position was the most successful method for identifying hymenal
      lacerations in both groups of girls. Of the 10 hymenal lacerations detected in
      the prepubertal girls 20% were identified during the use of the supine labial
      separation method, 60% with the supine labial traction technique, and 100% with
      the prone knee-chest position approach. Of the 49 hymenal lacerations detected in
      the pubertal girls 24% were identified with the supine labial separation method,
      65% with the supine labial traction technique, and 90% with the prone knee-chest
      position approach. The data from this study has shown that the results of a
      medical examination will vary by the method employed. CONCLUSIONS: While no
      single technique detected all the injuries, the use of the multimethod
      examination approach did prove to be a valuable adjunct in the evaluation of both
      the prepubertal and the pubertal girl's genitalia, particularly in the
      identification of a hymenal laceration. PRACTICE IMPLICATIONS: This approach uses
      three different examination methods: the supine labial separation method, the
      supine labial traction technique, and the prone knee-chest position. According to
      the results of this study, without the combined use of these three methods a
      significant number of injuries, particularly hymenal lacerations, could be missed
      in both the child and the adolescent.

PMID- 18329098
TI  - Differential gene expression in the honeybee head after a bacterial challenge.
AB  - Bidirectional interactions between the immune and nervous systems are well
      established in vertebrates. Insects show similar neuro-immune-behavioral
      interactions to those seen in vertebrates. Using quantitative real-time PCR, we
      present evidence that gene expression in the honeybee head is influenced by
      activation of the immune system 8h after a bacterial challenge with Escherichia
      coli. Seven genes were selected for quantitative analysis in order to cover both
      typical functions of the head such as exocrine secretion (mrjp3 and mrjp4) and
      olfactory processes (obp17) as well as more general processes such as structural
      functions (mlc2 and paramyosin), stress response (ERp60) and energy housekeeping
      (enolase). In this way, we show at the molecular level that the immune system
      functions as a sensory organ in insects -- as it does in vertebrates -- which
      signals to the head that a bacterial infection is present, and leads to
      regulation of expression of several genes in the head by a yet unidentified
      mechanism.

PMID- 18329099
TI  - Protein profiling of hemocytes from the terrestrial crustacean Armadillidium
      vulgare.
AB  - To establish and maintain a successful infection, microbial pathogens have
      evolved various strategies to infect the host in the face of a functional immune
      system. In this context, the alpha-proteobacteria Wolbachia capacities to infect
      new host species have been greatly evidenced. Indeed, in terrestrial isopods,
      experimentally transferred Wolbachia invade all host tissues, including immune
      cells such as hemocytes. To investigate mechanisms that have to be avoided by
      bacteria to maintain themselves in hemocytes, we characterized the hemocyte
      proteome of Armadillidium vulgare by a 2D gel electrophoresis approach. Fifty-six
      proteins were identified and classified into functional groups (stress and
      immunity, glucose metabolisms, cytoskeleton, others). We focused on immune
      response and cytoskeleton proteins often exploited by bacteria to invade their
      host. From the microsequences obtained by mass spectrometry, PCR primers were
      designed to amplify seven partial cDNAs encoding masquerade, alpha2
      macroglobulin, transglutaminase, MnSOD, calreticulin, cyclophilin, and vinculin,
      confirming their expression in hemocytes.

PMID- 18329100
TI  - Bovine WC1(-) gammadeltaT cells incubated with IL-15 express the natural
      cytotoxicity receptor CD335 (NKp46) and produce IFN-gamma in response to
      exogenous IL-12 and IL-18.
AB  - The gammadeltaT cells of ruminants are believed to participate in innate immunity
      and have been described with regulatory, inflammatory and cytotoxic functions.
      Here we describe a subset of CD3(+) TcR1(+) WC1(-)gammadeltaT cells expressing
      CD335 (NKp46), classically associated with CD3(-) natural killer (NK) cells, as a
      consequence of incubation with IL-15. This population, undetectable at the time
      of collection, developed after 2 week of IL-15 culture from splenic leukocytes
      (SPL) reaching greater than 50% of the total gammadeltaT cells. However, they did
      not grow well from peripheral blood leukocytes (PBL). Splenic gammadeltaT cells
      positively selected by magnetic separation prior to incubation with IL-15 and
      analyzed by flow cytometry, consistently yielded CD3(+) cells expressing CD335.
      These cells arose from the CD335(-)gammadeltaT cell population suggesting that
      the new population represents up-regulation of CD335 by gammadeltaT cells. CD335
      mRNA expression from sorted IL-15-incubated SPL CD335(+)gammadeltaT cells or NK
      cells exceeded that of CD335(-)gammadeltaT cells. Incubation with IL-12 and IL-18
      increased the number of CD335(+)gammadeltaT cells in both the PBL and SPL
      fractions as compared to controls or IL-12 or IL-18 alone. In addition,
      CD335(+)gammadeltaT cells demonstrated a robust ability to produce IFN-gamma in
      response to exogenous IL-12 and IL-18. Taken as a whole, we describe a new
      phenotypically distinct bovine gammadeltaT cell sub-population capable of
      participating in type 1 immune responses.

PMID- 18329101
TI  - Thymus-independent type 2 antigen induces a long-term IgG-related network memory.
AB  - Thymus-independent type 2 (TI-2) antigens occasionally induce long-lasting IgM
      memory, but do not prime for typical secondary IgG responses. However, contrary
      to current understanding, we detected several TI-2-induced long-term memory
      effects in subsequent thymus-dependent (TD) responses to the hapten 2
      phenyloxazolone coupled to a protein carrier. The early primary TD response, even
      3 months after TI-2 immunization, included non-mutated IgM as well as IgG
      antibodies exhibiting higher affinities than the Ox1 idiotype which dominates and
      has highest affinity in sole TD responses. The secondary exclusive IgG response 8
      weeks later contained major hitherto non-observed clones. Somatic hypermutation
      on the normally dominant V(H)Ox1 gene was largely silenced while the associated
      VkappaOx1 exhibited the classical affinity-enhancing mutations, thus suggesting a
      separate regulation of this process for V(H) and V(L) genes. Mutations
      accumulated in genes which normally are rarely or non-expressed or non-mutating.
      First evidence is presented that receptor revision by V(H) replacement may occur
      during immune maturation in genetically non-engineered wildtype mice. We conclude
      that the TI-2 antigen-induced altered selection of TD Ag-inducible clones and its
      severe gene-specific influence on further somatic mutations and affinity
      maturation represents a network memory, which we hypothesize to be mediated by
      anti-idiotypic regulatory T cells.

PMID- 18329102
TI  - Determination of water permeability of paramagnetic liposomes of interest in MRI
      field.
AB  - The water permeability of various liposome membranes has been determined at 298K
      by measuring the NMR longitudinal water proton relaxation rate of vesicles
      encapsulating the clinically approved Gd-HPDO3A complex (HPDO3A=10-(2
      hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). Two basic
      formulations based on DPPC (dipalmitoylphosphatidylcholine) and POPC (palmitoyl
      oleylphosphatidylcholine) phospholipids were selected and investigated.
      Furthermore, the permeability changes caused by the membrane incorporation of
      amphiphiles like cholesterol and/or metal complexes of interest for designing
      improved liposome-based MRI contrast agents, were also investigated. The
      incorporation of cholesterol and metal complexes bearing C18 saturated chains in
      POPC-based liposomes reduces the water diffusivity across the membrane bilayer.
      On the contrary, the incorporation of a macrocyclic metal complex bearing four
      C12 alkylic chains, one for each coordination arm of the ligand, considerably
      enhances the water permeability in DPPC-based liposomes. Finally, it is reported
      that the permeability of POPC-based bilayer is increased when the liposomes are
      subjected to an osmotic stress.

PMID- 18329103
TI  - The possible role of an [FeFe]-hydrogenase-like protein in the plant responses to
      changing atmospheric oxygen levels.
AB  - The knockdown of a [FeFe]-hydrogenase-like gene in the model plants Medicago
      truncatula and Arabidopsis thaliana resulted in a mutant with a dwarf phenotype.
      Surprisingly, the phenotype is undistinguishable from wild type under hypoxic
      conditions. The heterologous expression of the plant gene in Escherichia coli
      indicates that the resulting protein probably coordinates two [Fe-S] clusters
      with different magnetic properties. Sequence alignment analysis indicates that
      these two clusters would be topologically equivalent to the mesial and proximal
      [Fe-S] centers of [FeFe]-hydrogenases. A possible role of the gene product in
      oxygen signaling pathways is discussed.

PMID- 18329104
TI  - Metal-ion catalyzed polymerization in the eutectic phase in water-ice: a possible
      approach to template-directed RNA polymerization.
AB  - The emergence of an RNA world requires among other processes the non-enzymatic,
      template-directed replication of genetic polymers such as RNA or related nucleic
      acids, possibly catalyzed by metal-ions. The absence of uridilate derivative
      polymerization on adenine containing templates has been the main issue preventing
      an efficient template-directed RNA polymerization. We report here the
      investigation of template-directed RNA polymerization in the eutectic phase in
      water-ice. In particular, it was found that activated uridilate monomers in the
      presence of metal-ion catalysts could efficiently elongate RNA hairpins whose 5'
      overhangs served as the templating sequence. The same applies for every other
      pyrimidine and purine nucleobase. Moreover, the initial elongation rates were
      always higher in the presence of a template complementary to the nucleotide than
      in systems without proper base-pairing opportunities. These results suggest that
      a template-directed RNA polymerization catalyzed by metal-ions could be carried
      out under eutectic phase in water-ice conditions.

PMID- 18329105
TI  - Chimerism occurs in thyroid, lung, skin and lymph nodes of women with sons.
AB  - Chimerism indicates the presence of cells from one individual in another.
      Pregnancy and blood transfusions are considered the main sources for chimerism.
      Chimeric cells have been attributed a pathogenic role in various autoimmune
      diseases. However, data on the occurrence of chimeric cells in normal organs are
      scarce. In order to gain insight into the possible pathogenic potential of
      chimeric cells in autoimmune disease, it is necessary to determine the prevalence
      of chimeric cells in organs not affected by autoimmune disease. In situ
      hybridization for the Y-chromosome was performed on organs obtained at autopsy of
      51 women. We investigated 44 thyroid, 38 lung, 21 skin and 7 lymph node samples.
      All women had sons, and data from their blood transfusion histories were
      retrieved for at least 10 years before death. Slides were scored semi
      quantitatively for chimerism as low (1-3 Y-chromosome-positive cells per slide),
      moderate (4-10 positive cells per slide) or high (more than 10 positive cells per
      slide). Y-chromosome-positive cells were found in 8 thyroid, 10 lung, 3 skin and
      1 lymph node samples of 18 women. There was no association between the presence
      of chimeric cells and blood transfusion history. Most organs in which chimerism
      was present contained a small to moderate level. Thus, chimerism can occur in
      normal organs of women without autoimmune disease. Our results indicate that
      chimerism is not necessarily associated with disease.

PMID- 18329107
TI  - Intra-parotid facial nerve multiple plexiform neurofibroma in patient with NF1.
AB  - INTRODUCTION: Primary neurogenic tumours of facial nerve are uncommon with the
      majority found intra-temporally. Intracranial and intra-parotid neoplastic
      involvement of cranial nerve VII is much less common. There are 11 reported
      cases, in the English-language literature, of intra-parotid facial nerve
      plexiform neurofibromas with eight of them associated with NF1. MATERIALS AND
      METHODS: A child, 10 years old, with NF1, reached us for a cheek swelling, slowly
      increased in previous 8 years. At the age of 3 years, a plexiform neurofibroma
      was diagnosed by biopsy of the lesion. Clinical examination and NMR showed in the
      sub-cutaneous tissue of the right cheek, two contiguous nodular lesions, about 2
      cm x 1.5 cm in diameter; a third neoformed lesion, about 1cm in diameter, was
      located above the ipsilateral labial commissure. No facial nerve impairment was
      seen. The patient underwent superficial parotidectomy with removal of the lesions
      and preservation of the facial nerve. RESULTS: The patient had a considerable
      regional swelling in the immediate post-operative course; no facial nerve
      impairment was observed. The swelling of the cheek did not show a fully
      regression in the post-operative course. Ultrasonography at 3 months showed a
      recurrence of disease. DISCUSSION: Plexiform neurofibromas should be
      distinguished due to their risk of malignant transformation seen in up to 15% of
      patients affected by NF1. Surgery is the only effective option currently
      available for the treatment of PNF. However, success of surgical intervention is
      limited by the infiltrating nature of the tumours, resulting in a high rate of
      tumour re-growth. Facial nerve preservation during surgery is unlikely and
      significant morbidity can result from their excision. The age of the patient at
      surgical resection seemed to influence outcome: tumours resected before age 10
      years recurred in 60% of cases compared with only 30% recurrence in patients
      older than the age of 10 years. CONCLUSION: Indication and timing of surgery, in
      paediatrics patients with NF1, are complex. To avoid eventual physical and
      psychological consequences, it seems prudent to delay surgery as long as it is
      feasible for otherwise asymptomatic paediatric patients with facial plexiform
      neurofibroma.

PMID- 18329106
TI  - IL-13 induces the expression of the alternative activation marker Ym1 in a subset
      of testicular macrophages.
AB  - Macrophages are thought to play an important role in the maintenance of immune
      privilege in the testis, which functions to prevent immune responses to
      developing sperm. Two populations of macrophages are known to exist in the
      testis, one of which exhibits immunosuppressive activity. Macrophages that are
      alternatively activated with either IL-4 or IL-13 have been shown to be anti
      inflammatory and promote wound healing. Expression of the Ym1 protein is an
      established marker of alternatively activated macrophages. Testicular macrophages
      were examined for expression of Ym1 protein, and it was found to be highly
      expressed in a subpopulation of CD11b(+) cells. Furthermore, we have shown that
      Ym1 protein expression in the testis is dependent upon IL-13R signaling, and that
      IL-13 is produced in the testis. These data suggest that IL-13 plays a role in
      testicular immune privilege by the maintenance of an alternatively activated
      macrophage population.

PMID- 18329108
TI  - Multiplex microsphere immuno-detection of potato virus Y, X and PLRV.
AB  - To monitor seed potatoes for potato virus X, Y and PLRV, a multiplex microsphere
      immunoassay (MIA) was developed based on the Luminex xMAP technology, as an
      alternative to ELISA. The xMAP technology allowed detection of a number of
      antigens simultaneously whereas ELISA only allowed simplex detection of antigens.
      The use of paramagnetic beads in the MIA procedure allowed efficient removal of
      excess sample compounds and reagents. This resulted in lower background values
      and a higher specificity than a non-wash MIA procedure using conventional beads.
      In a simplex MIA detection, levels for PVY and PLRV in potato leaf extracts were
      10 times lower than ELISA but for PVX 10 timers higher, whereas the specificity
      was similar. Results of a multiplex assay performed on viruses added to potato
      leaf extracts were largely similar to those of ELISA for individual viruses.
      Results of samples infected naturally with PVX, PVY or PLRV were comparable with
      ELISA.

PMID- 18329109
TI  - Enhancement of the immunogenicity of an infectious bronchitis virus DNA vaccine
      by a bicistronic plasmid encoding nucleocapsid protein and interleukin-2.
AB  - A DNA vaccine against infectious bronchitis virus (IBV) can induce specific
      humoral and cell-mediated immunity. However, compared to conventional vaccines,
      DNA vaccines usually induce poor antibody responses. To develop a more potent IBV
      DNA vaccine formulations, a monocistronic vector encoding the nucleocapsid
      protein of IBV and a bicistronic vector separately encoding the nucleocapsid
      protein and immune-stimulatory interleukin-2 were constructed. When the DNA
      vaccines were administered to the quadriceps muscle of chickens, the induced
      humoral and cellular responses were evaluated. There was a significant difference
      in ELISA antibody levels elicited by either monocistronic or bicistronic DNA
      vaccines. The percentage of CD3+, CD3+CD8+ and CD3+CD4+ subgroups of peripheral
      blood T-lymphocytes in chickens immunized with bicistronic DNA vaccine were
      higher than those in chickens immunized with monocistronic DNA vaccine. When
      chickens were challenged with a virulent strain of IBV, the protective efficacy
      could be enhanced significantly after immunization with bicistronic DNA vaccine.
      These results demonstrated that bicistronic DNA vaccine is an effective approach
      to increase IBV DNA vaccine immunogenicity.

PMID- 18329110
TI  - The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good
      for?
AB  - Several theories have proposed possible functions of adult neurogenesis in
      learning processes on a systems level, such as the avoidance of catastrophic
      interference and the encoding of temporal and contextual information, and in
      emotional behavior. Under the assumption of such functionality of new neurons,
      the question arises: what are the consequences of adult hippocampal neurogenesis
      beyond the temporally immediate computational benefit? What might provide the
      evolutionary advantage of maintaining neurogenesis in the dentate gyrus but
      almost nowhere else? I propose that over the course of life, activity-dependently
      regulated adult neurogenesis reveals its true significance in the retained
      ability for lasting and cumulative network adaptations. The hippocampal precursor
      cells that generate new neurons with their particular acute function represent a
      'neurogenic reserve': the potential to remain flexible and plastic in hippocampal
      learning when the individual is exposed to novelty and complexity.

PMID- 18329111
TI  - Cortical excitation and chronic pain.
AB  - Investigation of the basic mechanisms of chronic pain not only provides insights
      into how the brain processes and modulates sensory information but also provides
      the basis for designing novel treatments for currently intractable clinical
      conditions. Human brain imaging studies have revealed new roles of cortical
      neuronal networks in chronic pain, including its unpleasant quality, and mouse
      studies have provided molecular and synaptic mechanisms underlying relevant
      cortical plasticity. This review paper will critically examine the current
      literature and propose a cortical network model for chronic pain.

PMID- 18329112
TI  - Intermittent hypoxia and sleep restriction: motor, cognitive and neurochemical
      alterations in rats.
AB  - The present study evaluated the effects of intermittent hypoxia (IH) and sleep
      restriction (SR) upon motor and cognitive function in rats. Also evaluated were
      catecholamine concentrations and tyrosine hydroxylase (TH) protein expression in
      different regions of the forebrain. Wistar Hannover rats were submitted to IH for
      4 days or 21 days (2 min room air to 2 min 10% O(2) for 10:00-16:00 h), followed
      by SR for 18 h (16:00-10:00 h). Rats were randomly assigned into four
      experimental groups: (1) control (2) IH (3) SR and (4) IH-SR. In the inhibitory
      avoidance task, an additional group of rats was submitted to paradoxical sleep
      deprivation (PSD) for 96 consecutive hours. Results showed that SR induced an
      increase in motor activity without modifying catecholaminergic turnover in the
      frontal cortex and striatum. The increase in exploratory activity in SR rats
      could be the result of impaired habituation. Neither SR periods induced cognitive
      deficits in the inhibitory avoidance task after 5 or 21 days. However, 96 h of
      PSD impaired acquisition/retention in rats. Exposure to IH did not affect motor
      and cognitive function but IH was associated with SR in increased motor activity.
      After 21 days, IH and IH-SR reduced striatal norepinephrine concentration
      although neither SR nor IH affected TH protein expression. The results presented
      here suggest that hypoxia and sleep loss exert distinct deleterious effects upon
      the central nervous system.

PMID- 18329113
TI  - Genes, plasticity and mental retardation.
AB  - Functional and structural plasticity is a fundamental property of the brain
      involved in diverse processes ranging from brain construction and repair to
      storage of experiences during lifetime. Our current understanding of different
      forms of brain plasticity mechanisms has advanced tremendously in the last
      decades, benefiting from studies of development and memory storage in adulthood
      and from investigations of diverse diseased conditions. In this review, we focus
      on the role of mental retardation (MR) genes and show how this developing area of
      research can enrich our knowledge of the cellular and molecular mechanisms of
      brain plasticity and cognitive functions, and of the dysfunctional mechanisms
      underlying MR. We describe two main groups of MR genes; those leading to
      dysfunctional neurodevelopmental programs and brain malformations, and those
      which rely on alterations in molecular mechanisms underlying synaptic
      organization and plasticity. We first explore the role of MR genes in key
      mechanisms of neurogenesis and neuronal migration during development and in the
      adult, such as actin and microtubule-cytoskeletal dynamics and signal
      transduction. We then define the contribution of MR genes to forms of activity
      dependent synaptic modifications, such as those involved in molecular
      organization of the synapse, intracellular signaling regulating gene programs and
      neuronal cytoskeleton to control network remodeling. We trace the characteristics
      of MR genes playing key roles in many forms of brain plasticity mechanisms, and
      highlight specific MR genes that endorse distinct roles in different cell types
      or brain regions, and at various times of a brain lifetime.

PMID- 18329114
TI  - Elevated chromogranin A (CgA) serum levels in the patients with advanced
      pancreatic cancer.
AB  - The neuroendocrine differentiation in PC could potentially represent a new
      finding with diagnostic, prognostic and therapeutic implications. This study
      aimed at evaluating the clinical usefulness of CgA as a neuroendocrine (NE) serum
      marker. We investigated the role of the serum concentration of CgA in a study
      group of patients with PC. CgA was significantly higher in the patients affected
      by PC as compared with the group of healthy subjects (HS) and those with chronic
      pancreatitis (CHP) (p<0.001). Also the HS group differed significantly from the
      CHP control group in the serum CgA levels (p<0.001). The serum carbohydrate
      antigen (CA19-9) level displayed a significant difference (p<0.001) between the
      PC and the HS group. The PC and CHP groups, as well as the HS and CHP groups
      showed also significant differences in the CA19-9 levels (p<0.001). One can
      conclude that the patients with higher CgA levels had poorer prognosis and
      survival, as compared to those with lower CgA levels. These results support the
      notion that the determination of serum CgA level before treatment may be a
      potential prognostic factor for PC.

PMID- 18329115
TI  - Prevalence and burden of gastrointestinal helminthes among local chickens, in
      northern Jordan.
AB  - We conducted a cross-sectional study from December 2004 to February 2005 and from
      June 2005 to August 2005. The study aimed to determine the prevalence of
      gastrointestinal and tracheal helminthes among local chickens in northern Jordan.
      A total of 208 male and female local scavenging chickens were selected randomly.
      We examined the trachea and gastrointestinal tract of each bird for the presence
      of helminthes. We recovered three nematode and eight cestode species. No
      trematodes were found. One hundred and fifty-two birds (73.1%) (95% CI: 67, 79)
      were infected. The prevalences of different species were as follows: Ascaridia
      galli female 28%, male 43%; Capillaria obsignata 0.5%; Heterakis gallinarum 33%;
      Amoebotaenia cuneata 4.3%; Choanotaenia infundibulum female 23%, male 13%;
      Davainea proglottina 1.4%; Hymenolepsis cantaniana 11%; Hymenolepsis carioca
      female 35%, male 24%; Raillietina cesticillius female 5%, male 11%; Raillietina
      echinobothrida 16%; and Raillietina tetragona 18%. The prevalences of A. galli
      and R. cesticillus were higher in male than female hosts while those of C.
      infundibulum and H. carioca were higher in females. The median worm burden was 7
      (range 0-168) worms per chicken.

PMID- 18329116
TI  - Real-Time PCR quantification of PAH-ring hydroxylating dioxygenase (PAH-RHDalpha)
      genes from Gram positive and Gram negative bacteria in soil and sediment samples.
AB  - Real-Time PCR based assays were developed to quantify Gram positive (GP) and Gram
      negative (GN) bacterial populations that are capable of degrading the polycyclic
      aromatic hydrocarbons (PAH) in soil and sediment samples with contrasting
      contamination levels. These specific and sensitive Real-Time PCR assays were
      based on the quantification of the copy number of the gene that encodes the alpha
      subunit of the PAH-ring hydroxylating dioxygenases (PAH-RHDalpha), involved in
      the initial step of the aerobic metabolism of PAH. The PAH-RHDalpha-GP primer set
      was designed against the different allele types present in the data base (narAa,
      phdA/pdoA2, nidA/pdoA1, nidA3/fadA1) common to the Gram positive PAH degraders
      such as Rhodococcus, Mycobacterium, Nocardioides and Terrabacter strains. The PAH
      RHDalpha-GN primer set was designed against the genes (nahAc, nahA3, nagAc, ndoB,
      ndoC2, pahAc, pahA3, phnAc, phnA1, bphAc, bphA1, dntAc and arhA1) common to the
      Gram negative PAH degraders such as Pseudomonas, Ralstonia, Commamonas,
      Burkholderia, Sphingomonas, Alcaligenes, Polaromonas strains. The PCR clones for
      DNA extracted from soil and sediment samples using the designed primers showed
      100% relatedness to the PAH-RHDalpha genes targeted. Deduced from highly
      sensitive Real-Time PCR quantification, the ratio of PAH-RHDalpha gene relative
      to the 16S rRNA gene copy number showed that the PAH-bacterial degraders could
      represent up to 1% of the total bacterial community in the PAH-contaminated
      sites. This ratio highlighted a positive correlation between the PAH-bacterial
      biodegradation potential and the PAH-contamination level in the environmental
      samples studied.

PMID- 18329117
TI  - Improved detection of recurrent laryngeal tumor after radiotherapy using (18)FDG
      PET as initial method.
AB  - BACKGROUND AND PURPOSE: Timely detection of recurrent laryngeal tumor after
      radiation is an important predictive factor for curation as well as preservation
      of laryngeal function. Direct laryngoscopy under general anesthesia with taking
      of biopsies is the standard diagnostic procedure to detect recurrence when
      suspicion is raised. This, however, is an invasive and potentially damaging
      technique. Hence, a non-invasive diagnostic procedure, such as (18)FDG-PET to
      stratify patients for direct laryngoscopy could be useful. (18)FDG-PET is
      interpreted visually so that observer variation may affect clinical practice. In
      the present study, we therefore investigated this aspect of reproducibility.
      PATIENTS AND METHODS: Thirty consecutive patients suspected of recurrent
      laryngeal carcinoma after radiotherapy underwent (18)FDG-PET and direct
      laryngoscopy under general anesthesia with taking of biopsies. (18)FDG-PET scans
      were reported by nine nuclear medicine physicians and residents, using a three
      point scaling system. The reference was the absence or appearance of a local
      recurrence in the 12 months following (18)FDG-PET. RESULTS: Eight patients had
      biopsy proven recurrent laryngeal carcinoma. Sensitivity of (18)FDG-PET was 88%
      (95% CI 53-98%) and specificity was 82% (95% CI 62-93%). The observers had a
      moderate to reasonable agreement (weighted kappa 0.45 (95% CI 0.20-0.69)) vs. the
      clinical gold standard and interobserver kappa was 0.54 (95% CI 0.40-0.69).
      CONCLUSION: (18)FDG-PET seems to be a promising technique to detect recurrent
      laryngeal carcinoma after radiotherapy, and selecting patients for direct
      laryngoscopy. This will avoid futile invasive procedures. Interobserver agreement
      and variability is reasonable using this technique, but training is necessary.
      Studies comparing different strategies to select patients for direct laryngoscopy
      in case of suspected recurrence are warranted.

PMID- 18329118
TI  - Scintigraphy in prediction of the salivary gland function after gland-sparing
      intensity modulated radiation therapy for head and neck cancer.
AB  - BACKGROUND AND PURPOSE: To evaluate salivary gland scintigraphy in prediction of
      salivary flow following radiation therapy. PATIENTS AND METHODS: Twenty patients
      diagnosed with head and neck cancer were treated with intensity modulated
      radiation therapy with an intention to spare the salivary gland function. The
      total quantitative saliva secretion was measured prior to and 6 and 12 months
      after therapy, and the function of the major salivary glands was monitored using
      Tc-99m-pertechnetate scintigraphy. Two models were designed for prediction of the
      post-treatment salivary flow: an average model, based on the average proportions
      of saliva produced by each of the four major glands in healthy subjects, and an
      individual model, based on saliva produced by each gland as measured by
      scintigraphy prior to therapy. These models were compared with volume-based
      (Lyman) normal tissue complication probability models using two published sets of
      model parameters. RESULTS: The D(50) for the parotid and the submandibular gland
      function assessed at 6 and 12 months after radiotherapy was approximately 39Gy.
      The scintigraphy-based individual model predicted well the measured post
      treatment saliva flow rates. The correlation coefficient between the predicted
      stimulated and the measured saliva flow rate was 0.77 (p<0.0001) at 6 months and
      0.55 (p=0.034) at 12 months after completion of radiotherapy. The relative
      changes in unstimulated and stimulated salivary flow rates showed similar
      dependency on the cumulative radiation dose. CONCLUSIONS: Salivary gland function
      assessed by scintigraphy prior to radiotherapy is useful in prediction of the
      residual salivary flow after radiotherapy.

PMID- 18329119
TI  - On-line rapid palliation using helical tomotherapy: a prospective feasibility
      study.
AB  - Rapid delivery of radiation therapy is expected to benefit patients requiring
      palliation. We investigated the feasibility of employing a helical tomotherapy
      unit to scan, plan, and deliver a radiation treatment in a single radiation
      therapy appointment. Eleven patients each had an MVCT scan acquired, a plan
      created, and delivery completed while the patient was on the treatment couch.
      Timelines for each step of the process were recorded for each patient, and
      compared with the conventional process for similar patients. Preliminary results
      show that patients routinely can be treated within a 1 hour appointment for the
      first fraction.

PMID- 18329120
TI  - Ischemia induces cell proliferation and neurogenesis in the gerbil hippocampus in
      response to neuronal death.
AB  - We studied hippocampal cellular proliferation and neurogenesis processes in a
      model of transient global cerebral ischemia in gerbils by labelling dividing
      cells with 5'-Bromo-2'-deoxyuridine (BrdU). Surrounding the region of selective
      neuronal death (CA1 pyramidal layer of the hippocampus), an important increase in
      reactive astrocytes and BrdU-labelled cells was detected 5 days after ischemia. A
      similar result was found in the dentate gyrus (DG) 12 days after ischemia. The
      differentiation of the BrdU+ cells was investigated 28 days after BrdU
      administration by analyzing the morphology, anatomic localization and cell
      phenotype by triple fluorescent labelling (BrdU, adult neural marker NeuN and DNA
      marker TOPRO-3) using confocal laser-scanning microscopy. This analysis showed
      increased neurogenesis in the DG in case of ischemia and triple positive
      labelling in some newborn cells in CA1. Seven brain hemispheres from gerbils
      subjected to ischemia did not develop CA1 neuronal death; hippocampus from these
      hemispheres did not show any of the above mentioned findings. Our results
      indicate that ischemia triggers proliferation in CA1 and neurogenesis in the DG
      in response to CA1 pyramidal neuronal death, independently of the reduced
      cerebral blood flow or the cell migration from subventricular zone (SVZ).

PMID- 18329121
TI  - Categorization of biologically significant objects, food and gender, in rhesus
      monkeys. I. Behavioral study.
AB  - Macaque monkeys have a highly evolved visual system comparable to that of humans.
      One of the important visual functions is performing discriminations among
      biologically significant objects such as food or heterosexual partners. In the
      present study, we examined whether rhesus monkeys could categorize two
      dimensional images related to food or gender using a visual discrimination task.
      Three rhesus monkeys were trained to make distinctions of food from non-food
      items, and between male and female monkeys, using 60 or more different pictures
      of each category. After more than 9 months of training, the monkeys discriminated
      a variety of foods from non-food and different males from females with more than
      80% accuracy, even when the stimuli were used for the first time or presented
      only once in a session. The proportion of correct responses and response
      latencies showed better performance in discrimination of food/non-food than that
      of gender. The results suggest that rhesus monkeys are able to perform visual
      discrimination of highly abstract biologically significant categories with better
      performance in a food-related category than a gender-related one, using two
      dimensional visual information.

PMID- 18329122
TI  - Recombinant human gelatin nanoparticles as a protein drug carrier.
AB  - Considerable attention has been directed to the application of natural gelatin
      based nanoparticles. However, there are still critical problems associated with a
      safety issue of animal-origin gelatins, heterogeneous molecular weight,
      subsequent nanoparticle size distributions and use of toxic cross-linker. The
      purpose of this study was to develop a simple, safe and reproducible preparation
      method of recombinant human gelatin (rHG) nanoparticles via a modified
      desolvation method using a natural cross-linker for protein drug delivery. The
      model protein, FITC-BSA, was released from rHG nanoparticles in a biphasic and
      sustained-release pattern without initial burst. Optimized nanoparticles based on
      rHG and a natural cross-linker were prepared for the first time and showed great
      potential for protein drug delivery in terms of sustained release, less initial
      burst, and safety. In addition, rHG nanoparticles were efficiently internalized
      in the cell and mainly localized in the cytoplasm without significant
      cytotoxicity. Overall, these results suggest that rHG nanoparticles are
      appropriate for a protein drug delivery system with minimal toxicity.

PMID- 18329123
TI  - All-cause mortality in insulin-treated diabetic patients: a 20-year follow-up.
AB  - AIMS: To establish all-cause mortality rates, and risk factors for mortality in
      insulin-treated diabetic individuals living in Canterbury, New Zealand. METHODS:
      Insulin-treated diabetic subjects (n=995) on the Canterbury Diabetes Registry
      were followed up over 20-year and vital status determined. Death rates were
      standardised and hazard regression was used to model the effects of demographic
      covariates on relative survival time. RESULTS: Six subjects had emigrated, the
      remaining 989 diabetic subjects contributed a total of 13705.53 person-years of
      follow-up, a mean of 13.7 years per subject. During follow-up 525 deaths occurred
      in subjects' aged 17.3-96.7, (261 females, 264 males). All-cause mortality rates
      in diabetic subjects exceeded those in the general population at all ages. SMRs
      were slightly higher for females than males in almost all age-at-onset groups,
      being 2.48 (95% CI: 2.18-2.78) for females and 2.17 (95% CI: 1.91-2.43) for males
      overall, but reaching a peak in the <30 age at onset group for both females and
      males being 4.25 (3.07-5.44) and 3.26 (2.49-4.03), respectively. CONCLUSIONS:
      Mortality rates for diabetic individuals remain high, resulting in shortened life
      spans relative to the general population. This study provides a baseline for
      further studies of mortality and changes in mortality within New Zealand.

PMID- 18329124
TI  - Cause-specific mortality in insulin-treated diabetic patients: a 20-year follow
      up.
AB  - BACKGROUND: Diabetes is one of the most common chronic diseases in Western
      populations. There have been few large published cohort studies of diabetes with
      20 years of follow-up worldwide, and none other than the present one in NZ. AIMS:
      To establish cause-specific death rates, by age and sex in insulin-treated
      diabetic individuals living in Canterbury, NZ. METHODS: Insulin-treated diabetic
      subjects on the Canterbury Diabetes Registry were followed over 20 years and
      vital status determined. Following notification of deaths, age- and sex-specific
      mortality rates, and sex-specific mortality ratios (SMRs) were calculated.
      RESULTS: During follow-up 966 diabetic subjects contributed 13,495 person-years
      and 525 deaths occurred (261 females and 264 males). At all ages mortality rates
      were considerably higher than expected mortality. Relative mortalities were
      increased for cardiovascular (SMR women 3.73, 95% CI: 3.16-4.30; men 3.27, 95%
      CI: 2.76-3.78), renal (SMR women 5.55, 95% CI: 2.53-8.57; men 7.15, 95% CI: 3.40
      10.90), respiratory disease (SMR women 3.31, 95% CI: 1.98-4.63; men 2.32, 95% CI:
      1.41-3.23) and malignancy (SMR women 4.99, 95% CI: 2.99-6.99; men 2.19, 95% CI:
      1.42-2.96) with cardiovascular disease accounting for the single greatest cause
      of excess death at all ages. CONCLUSIONS: Mortality rates for diabetic
      individuals remain high, resulting in shortened life spans relative to the
      general population. To reduce these death rates attention must be paid to the
      early detection and treatment of CVD and associated risk factors.

PMID- 18329125
TI  - The presence of steatosis and elevation of alanine aminotransferase levels are
      associated with fibrosis progression in chronic hepatitis C with non-response to
      interferon therapy.
AB  - BACKGROUND/AIMS: Interferon (IFN) therapy leads to regression of hepatic fibrosis
      in chronic hepatitis C patients who achieve a sustained virologic response (SVR),
      while the beneficial effect is limited in those who fail to do so. The aim of the
      present study was to define factors associated with progression of fibrosis in
      patients who do not achieve a SVR. METHODS: Fibrosis staging scores were compared
      between paired liver biopsies before and after IFN in 97 chronic hepatitis C
      patients who failed therapy. The mean interval between biopsies was 5.9 years.
      Factors associated with progression of fibrosis were analyzed. RESULTS: Fibrosis
      progressed in 23%, remained unchanged in 47% and regressed in 29%. Steatosis and
      a high average alanine aminotransferase (ALT) between biopsies were independent
      factors for progression of fibrosis with risk ratios of 5.53 and 4.48,
      respectively. Incidence and yearly rate of progression of fibrosis was 64% and
      0.22+/-0.29 fibrosis units per year in those with both risk factors compared to
      8% and -0.04+/-0.17 fibrosis units per year in those negative for both factors.
      CONCLUSIONS: Hepatic steatosis and elevated ALT levels are risk factors for
      progression of fibrosis in chronic hepatitis C patients who fail to achieve a SVR
      to IFN therapy and therefore may be therapeutic targets to halt the potentially
      progressive disease.

PMID- 18329126
TI  - Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of
      HBeAg-positive chronic hepatitis B.
AB  - BACKGROUND/AIMS: We aimed to evaluate nucleoside/nucleotide combination therapy
      in treatment-naive HBeAg-positive patients with chronic hepatitis B (CHB).
      METHODS: One hundred and fifteen HBeAg-positive patients received lamivudine 100
      mg daily plus placebo (monotherapy) or lamivudine 100 mg plus adefovir dipoxil 10
      mg daily (combination therapy) for 104 weeks in a randomized double-blind study.
      RESULTS: Time-weighted average change in serum HBV DNA from baseline up to week
      16 was -4.20 log(10)copies/mL for both groups (p=0.936). At week 104, median
      serum HBV DNA change from baseline (log(10)copies/mL) for monotherapy and
      combination therapy was -3.41 versus -5.22, respectively. HBV DNA breakthrough
      was detected in 44% of monotherapy and 19% of combination therapy patients. The
      M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group,
      respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the
      monotherapy group and 45% (23/51) in the combination therapy group (p=0.018). By
      week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of
      combination therapy patients. Both regimens were well tolerated. CONCLUSIONS:
      Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher
      rates of ALT normalization were seen in the combination therapy group after two
      years. However, serological outcomes were similar.

PMID- 18329127
TI  - Ballooned hepatocytes in steatohepatitis: the value of keratin
      immunohistochemistry for diagnosis.
AB  - BACKGROUND/AIMS: Hepatocyte "ballooning" is an often used but ill defined term in
      liver pathology to designate a special form of liver cell degeneration associated
      with cell swelling and enlargement found particularly in steatohepatitis.
      Alterations of the intermediate filament cytoskeleton of the hepatocyte may
      contribute to the pathogenesis of this microscopic change. Ballooning
      degeneration is considered a hallmark of steatohepatitis, but enlarged
      hepatocytes may also be observed in a variety of other acute and chronic liver
      diseases. METHODS: The intermediate filament cytoskeleton was investigated using
      keratin 8 and 18 immunohistochemistry in liver diseases associated with enlarged
      or ballooned hepatocytes. RESULTS: Keratin 8/18 immunostaining was drastically
      reduced or lost in the cytoplasm of ballooned hepatocytes in alcoholic and non
      alcoholic steatohepatitis, chronic cholestatic conditions, ischemia/reperfusion
      injury and in ballooned hepatocytes in chronic hepatitis C cases with concurrent
      steatohepatitis. In contrast, substantial decrease or loss of keratin 8/18
      immunostaining was not noted in cases of acute hepatitis, giant cell hepatitis,
      chronic hepatitis B, or autoimmune hepatitis. CONCLUSIONS: Loss of keratin 8/18
      immunostaining can serve as an objective marker of a specific type of ballooning
      degeneration of hepatocytes. Oxidative stress may be a common denominator in the
      pathogenesis of keratin filament alterations in these conditions.

PMID- 18329128
TI  - Growth retardation versus overgrowth: Silver-Russell syndrome is genetically
      opposite to Beckwith-Wiedemann syndrome.
AB  - Human growth is a complex process that requires the appropriate interaction of
      many players. Central members in the growth pathways are regulated epigenetically
      and thereby reflect the profound significance of imprinting for correct mammalian
      ontogenesis. In this review, we show that the growth retardation disorder Silver
      Russell syndrome (SRS) is a suitable model to decipher the role of imprinting in
      growth. As we will show, SRS should not only be regarded as the genetically (and
      clinically) opposite disease to Beckwith-Wiedemann syndrome, but it also
      represents the first human disorder with imprinting disturbances that affect two
      different chromosomes (i.e. chromosomes 7 and 11). Thus, a functional interaction
      between factors encoded by chromosomes 7 and 11 is likely.

PMID- 18329129
TI  - The functional consequences of alternative promoter use in mammalian genomes.
AB  - We are beginning to appreciate the increasing complexity of mammalian gene
      structure. A phenomenon that adds an important dimension to this complexity is
      the use of alternative gene promoters that drive widespread cell type, tissue
      type or developmental gene regulation. Recent annotations of the human genome
      suggest that almost one half of the protein-coding genes contain alternative
      promoters, including those of many disease-associated genes. Aberrant use of one
      promoter over another has been found to be associated with various diseases,
      including cancer. Here we discuss the functional consequences of use and misuse
      of alternative promoters in normal and disease genomes and review the molecular
      mechanisms regulating alternative promoter use in mammalian genomes.

PMID- 18329130
TI  - Commentary: Diet and acne.

PMID- 18329131
TI  - Onset of alopecia areata after Epstein-Barr virus infectious mononucleosis.
AB  - BACKGROUND: The pathogenesis of alopecia areata (AA) is incompletely known. A
      positive family history in some points to a genetic predisposition, and
      discordance of the disease in identical twins suggests environmental triggers
      exist. OBJECTIVE: We sought to determine whether the Epstein-Barr virus (EBV) is
      a possible environmental trigger for AA. METHODS: We queried the National AA
      Registry for all patients who self-reported sudden onset of AA with concurrent
      EBV mononucleosis. RESULTS: Among the 6256 individuals registered between
      December 2001 and August 2007, 1586 patients reported an environmental trigger
      including 12 individuals who had an EBV infection within 6 months before the
      onset of AA. LIMITATIONS: This study relies on self-reported data, and not all
      medical records confirming EBV infections were available for review. CONCLUSION:
      The association between EBV and AA is worthy of further investigation.

PMID- 18329132
TI  - Hot hospitals and what happened to wash, rinse and dry? Recent changes to
      cleaning, disinfection and environmental ventilation.

PMID- 18329133
TI  - The difference in serotypes between extended-beta-lactamase (ESBL) and non-ESBL
      producing E. coli blood culture isolates at a UK district general hospital.

PMID- 18329134
TI  - Strategies for the prevention of hospital-acquired infections in the neonatal
      intensive care unit.
AB  - Nosocomial infections are among the leading causes of mortality and morbidity in
      neonatal intensive care units. Prevention of healthcare-associated infections is
      based on strategies that aim to limit susceptibility to infections by enhancing
      host defences, interrupting transmission of organisms by healthcare workers and
      by promoting the judicious use of antimicrobials. Several strategies are
      available and include: hand hygiene practices; prevention of central venous
      catheter-related bloodstream infections; judicious use of antimicrobials for
      therapy and prophylaxis; enhancement of host defences; skin care; and early
      enteral feeding with human milk.

PMID- 18329135
TI  - Cluster of nosocomial campylobacteriosis, Austria 2006.

PMID- 18329136
TI  - Matching criteria in case-control studies on postoperative infections.
AB  - Matching is commonly used in case-control studies to control for the effect of
      major confounding factors. We evaluated the available evidence from case-control
      studies regarding postoperative infections to identify how frequently matching
      was performed and with what specific variables. We searched for relevant case
      control studies in PubMed until August 2006 and further evaluated those that used
      individual matching between cases and controls. We identified and evaluated 42
      relevant studies. Age was used as a matching criterion in 27 of these 42 (64.3%)
      case-control studies. The specific type of surgical procedure was the second most
      commonly used criterion in 17 of 42 studies (40.5%). Gender was used in 14/42
      studies (33.3%) as a matching criterion between case and control patients. The
      period at risk for development of surgical site and/or other postoperative
      infections, i.e. time from surgery to the diagnosis of infection, was used in
      nine of 42 studies (21.4%), as was date of operation, and the primary diagnosis
      that led the case and control patients to surgery. The same surgeon or surgical
      team was used in seven studies (16.7%); matching according to the National
      Nosocomial Infection Surveillance system risk score was performed in five studies
      (11.9%). The findings of our analysis suggest that various characteristics are
      used for matching in case-control studies of postoperative infections. A more
      consistent use of matching with the specific type of surgical procedure may help
      in increasing the internal validity of a case-control study in this field of
      clinical research.

PMID- 18329137
TI  - Infection control as a major World Health Organization priority for developing
      countries.
AB  - Healthcare-associated infection affects hundreds of millions of people worldwide
      and is a major global issue for patient safety. It complicates between 5 and 10%
      of admissions in acute care hospitals in industrialised countries. In developing
      countries, the risk is two to twenty times higher and the proportion of infected
      patients frequently exceeds 25%. A growing awareness of this problem prompted the
      World Health Organization to promote the creation of the World Alliance for
      Patient Safety. Prevention of healthcare-associated infection is the target of
      the Alliance First Global Patient Safety Challenge, 'Clean Care is Safer Care',
      launched in October 2005. After 2 years, a formal statement has been signed by 72
      ministries of health as a pledge of their support to implement actions to reduce
      healthcare-associated infection; of these, 30 are developing countries.
      Additional countries, mostly from the developing world, have planned to sign by
      the end of 2008 and will represent in total more than three-quarters of the
      world's population. Given the emphasis of the proposed strategy on simple and
      affordable solutions, the impact of the Challenge is expected to be high in
      developing countries. The combined efforts expected under the Challenge have the
      potential to save millions of lives, prevent morbidities and long-term disability
      for hundreds of millions of patients, and lead to major cost savings through the
      improvement of basic infection control measures in any healthcare setting,
      regardless of resources available or level of development.

PMID- 18329138
TI  - Implementation of an infection control programme to limit the spread of extended
      spectrum beta-lactamase-producing Enterobacteriaceae in a Belgian university
      hospital.

PMID- 18329139
TI  - Outbreaks of nosocomial candidiasis in France 1996-2006.

PMID- 18329140
TI  - QSAR study on tetrahydroquinoline analogues as plasmodium protein
      farnesyltransferase inhibitors: a comparison of rationales of malarial and
      mammalian enzyme inhibitory activities for selectivity.
AB  - The quantitative structure-activity relationships of Plasmodium falciparum and
      Rat protein farnesyltransferase (PFT) inhibitory activities of 6-cyano-1-(3
      methyl-3H-imidazoly-4-ylmethyl)-3-substituted-1,2,3,4-tetrahydroquinoline (THQ)
      analogues are investigated in order to explore the similarities/deviations
      between the two enzymes for these analogues. The structure space of a ligand (BMS
      214662) bound to Rat-PFT (PDB code 1SA5) has been used as the conformational
      space of the compounds under investigation. The study has been carried out using
      the combinatorial protocol in multiple linear regression with several 2D- and 3D
      descriptors from molecular operating environment (MOE) representing the
      physicochemical and electronic features of the compounds. The molecular potential
      energy and partially charged van der Waals surface areas have taken part in the
      PFT models. They suggested in favor of molecular arrangement with minimum energy
      and low positively/negatively charged surfaces for optimum Pf-PFT inhibitory
      activity. Furthermore, less hydrophobic compounds are preferred for the activity.
      The Rat-PFT inhibitory activity models suggested in favor of more negatively as
      well as more positively charged surface area descriptors for the better activity.
      The PLS analysis carried out on the descriptors of the Pf-PFT and Rat-PFT models
      suggested that among the parameters, the partially charged surface areas in the
      range -0.20 to -0.15 (PEOE_VSA-3) and -0.30 to -0.25 (PEOE_VSA-5), hydrophobicity
      (a_hyd, logP(o/w) and SlogP_VSA4), and electronic energy (PM3_Eele) of the
      molecules hold promise for modulating the Pf-PFT/R-PFT inhibitory activities of
      the compounds. This suggested the possibility of modulating the Pf-PFT/R-PFT
      inhibitory activities and bringing about selectivity in the THQ analogues for the
      malarial parasite enzyme.

PMID- 18329141
TI  - [Non tuberculous mycobacterial infections].
AB  - PURPOSE: Non tuberculous mycobacterial (NTM) infections, also called atypical
      mycobacterial infections, are caused by environmental mycobacteria and usually
      occur in cases of general or local immunosupression. These infections usually
      concern the lungs, the lymphatic system, the skin or the bones tissues. They are
      sometimes disseminated. In spite of new efficient antibiotics, including
      macrolides, therapeutic failures are common and favoured by long treatments with
      their potential adverse effects and drug interactions. CURRENT KNOWLEDGE AND KEY
      POINTS: The prevalence of atypical mycobacterial infections is increasing and is
      also observed in internal medicine and geriatric wards. Their clinical expression
      can be varied. Nowadays, these infections are more and more frequent in non
      infected HIV patients, whether immunosupressed or not. Concerning other
      localisations of atypical mycobacterial infections, iatrogenic causes seem to be
      increasing and cases of nosocomial transmissions have also been described. When a
      NTM is found in a sample, its role in the cause of an infection must be assessed
      with criterias distinguishing infection from colonisation. FUTURE PROSPECTS AND
      PROJECTS: For those who are not locally or generally immunosupressed, it is
      important to search for an immunological deficiency. Indeed, patients having
      congenital deficiencies occurring in the interferon and interleukine pathways can
      develop repeated NTM infections. Therefore, for pulmonary infections in treatment
      failure and for disseminated infections, an adjuvant treatment by interferon
      gamma could be proposed. New molecules have recently been tested and can be used
      in some atypical mycobacterial infections.

PMID- 18329142
TI  - [Fahr syndrome discovered following a bacterial meningitis].
AB  - Fahr's disease refers to a rare syndrome characterized by symmetrical and
      bilateral intracranial calcifications. The basal ganglia and dentate nucleus are
      the most common site of involvement and most cases present extrapyramidal
      symptoms. This disease is mostly associated with a phosphocalcic metabolism
      disorder, especially to hypoparathyroidism. The authors report a case of Fahr
      syndrome (FS) discovered when a young patient with hypocalcemia and bacterial
      meningitis had a cerebral CT scan disclosing intracerebral calcifications. She
      fully recovered after both meningitis and hypocalcemia were treated.

PMID- 18329143
TI  - Estimating the amount and distribution of radon flux density from the soil
      surface in China.
AB  - Based on an idealized model, both the annual and the seasonal radon ((222)Rn)
      flux densities from the soil surface at 1099 sites in China were estimated by
      linking a database of soil (226)Ra content and a global ecosystems database.
      Digital maps of the (222)Rn flux density in China were constructed in a spatial
      resolution of 25 km x 25 km by interpolation among the estimated data. An area
      weighted annual average (222)Rn flux density from the soil surface across China
      was estimated to be 29.7+/-9.4 mBq m(-2)s(-1). Both regional and seasonal
      variations in the (222)Rn flux densities are significant in China. Annual average
      flux densities in the southeastern and northwestern China are generally higher
      than those in other regions of China, because of high soil (226)Ra content in the
      southeastern area and high soil aridity in the northwestern one. The seasonal
      average flux density is generally higher in summer/spring than winter, since
      relatively higher soil temperature and lower soil water saturation in
      summer/spring than other seasons are common in China.

PMID- 18329144
TI  - Methods for calculating dose conversion coefficients for terrestrial and aquatic
      biota.
AB  - Plants and animals may be exposed to ionizing radiation from radionuclides in the
      environment. This paper describes the underlying data and assumptions to assess
      doses to biota due to internal and external exposure for a wide range of masses
      and shapes living in various habitats. A dosimetric module is implemented which
      is a user-friendly and flexible possibility to assess dose conversion
      coefficients for aquatic and terrestrial biota. The dose conversion coefficients
      have been derived for internal and various external exposure scenarios. The
      dosimetric model is linked to radionuclide decay and emission database,
      compatible with the ICRP Publication 38, thus providing a capability to compute
      dose conversion coefficients for any nuclide from the database and its daughter
      nuclides. The dosimetric module has been integrated into the ERICA Tool, but it
      can also be used as a stand-alone version.

PMID- 18329145
TI  - Slow growth of Empetrum nigrum in industrial barrens: combined effect of
      pollution and age of extant plants.
AB  - We studied the impact of industrial pollution on population demography (age
      structure), growth and reproduction of crowberry, Empetrum nigrum L. Crowberry
      growing in severely polluted sites near non-ferrous smelters (at Harjavalta,
      Monchegorsk and Nikel) was on average twice as old as in unpolluted habitats, as
      indicated by the number of annual rings at root collar. Shoot length decreased
      both with plant ageing and due to pollution impact, while neither the proportion
      of generative plants nor berry production was affected by pollution or plant age.
      Our results suggest that death of the extant individuals of E. nigrum near the
      non-ferrous smelters is to a large extent explained by age-related damage of the
      main stem accelerated by pollution. Since vegetative propagation, seed
      germination and seedling establishment are hampered by soil toxicity, E. nigrum
      populations near the smelters continue to decline with ageing in spite of the
      gradual decline of emissions.

PMID- 18329146
TI  - Posttraumatic stress disorder: an empirical evaluation of core assumptions.
AB  - The diagnosis of posttraumatic stress disorder (PTSD) rests on several core
      assumptions, particularly the premise that a distinct class of traumatic events
      is linked to a distinct clinical syndrome. This core assumption of specific
      etiology ostensibly distinguishes the PTSD diagnosis from virtually all other
      psychiatric disorders. Additional attempts to distinguish PTSD from extant
      conditions have included searches for distinctive markers (e.g., biological and
      laboratory findings) and hypothesized underlying mechanisms (e.g., fragmentation
      of traumatic memory). We review the literature on PTSD's core assumptions and
      various attempts to validate the construct within a nomological network of
      distinctive correlates. We find that virtually all core assumptions and
      hypothesized mechanisms lack compelling or consistent empirical support. We
      consider the implications of these findings for conceptualizing PTSD in the
      forthcoming edition of the American Psychiatric Association's diagnostic manual.

PMID- 18329147
TI  - The economic impact of chronic diseases: how do households respond to shocks?
      Evidence from Russia.
AB  - The epidemiological burden of chronic diseases is increasing worldwide and there
      is very little empirical evidence regarding the economic impact of chronic
      diseases on individuals and households. The primary objective of this paper is to
      explore the evidence on how chronic diseases affect household healthcare
      expenditure, non-health consumption, labour (earned) income, and to demonstrate
      how transfers may provide some insurance against shocks from chronic diseases. We
      have explicated a two-part Heckit model on household level data obtained from the
      Living Standard Measurement Surveys (LSMS) from Russia to control for nontrivial
      proportion of zeros in the dependent variables, skewed distribution of
      expenditure data and endogeneity. The results indicate that chronic diseases are
      significantly associated with higher levels of household healthcare expenditure
      in Russia and productivity losses reflected by reduced labour supply and reduced
      household labour income. Non-healthcare expenditure also increased. Results
      suggest that households are able to insure non-health consumption against chronic
      diseases, possibly from transfers, which also increased. In addition,
      socioeconomic status indicators significantly explained the impact of chronic
      diseases on households. Insurance and higher average education in households were
      associated with higher healthcare expenditure. Household transfers were
      significant in Russia despite an appreciable level of insurance cover. We
      conclude that households depend on informal coping mechanisms in the face of
      chronic diseases, irrespective of insurance cover. These results have
      implications for policies regarding the financing of treatment and control of
      chronic diseases in the country studied.

PMID- 18329148
TI  - Neighborhoods and disability in later life.
AB  - This paper uses the US Health and Retirement Study to explore linkages between
      neighborhood conditions and stages of the disablement process among adults aged
      55 years and older in the United States. We consider multiple dimensions of the
      neighborhood including the built environment as well as social and economic
      conditions. In doing so, we use factor analysis to reduce indicators into eight
      neighborhood scales, which we incorporate into two-level logistic regression
      models along with controls for individual-level factors. We find evidence that
      economic conditions and the built environment, but not social conditions, matter.
      Neighborhood economic advantage is associated with a reduced risk of lower body
      limitations for both men and women. We also find for men that neighborhood
      economic disadvantage is linked to increased chances of reporting personal care
      limitations, particularly for those aged 55-64 years, and that high connectivity
      of the built environment is associated with reduced risk of limitations in
      instrumental activities. Our findings highlight the distinctive benefits of
      neighborhood economic advantage early in the disablement process. In addition,
      findings underscore the need for attention in the design and evaluation of
      disability-prevention efforts to the benefits that accrue from more physically
      connected communities and to the potential harm that may arise in later life from
      living in economically disadvantaged areas.

PMID- 18329149
TI  - Ownership, control, and contention: challenges for the future of healthcare in
      Malaysia.
AB  - The recent history of healthcare privatisation and corporatisation in Malaysia,
      an upper middle-income developing country, highlights the complicit role of the
      state in the rise of corporate healthcare. Following upon the country's
      privatisation policy in the 1980s, private capital made significant inroads into
      the healthcare provider sector. This paper explores the various ownership
      interests in healthcare provision: statist capital, rentier capital, and
      transnational capital, as well as the contending social and political forces that
      lie behind state interests in the privatisation of healthcare, the growing
      prominence of transnational activities in healthcare, and the regional
      integration of capital in the healthcare provider industry. Civil society
      organizations provide a small but important countervailing force in the
      contention over the future of healthcare in the country. It is envisaged that the
      healthcare financing system will move towards a social insurance model, in which
      the state has an important regulating role. The important question, therefore, is
      whether the Malaysian government, with its vested interests, will have the
      capacity and the will to play this role in a social insurance system. The issues
      of ownership and control have important implications for governance more
      generally in a future healthcare system.

PMID- 18329150
TI  - Stimulus timing by people with Parkinson's disease.
AB  - Previous literature suggests that Parkinson's disease is marked by deficits in
      timed behaviour. However, the majority of studies of central timing mechanisms in
      patients with Parkinson's disease have used timing tasks with a motor component.
      Since the motor abnormalities are a defining feature of the condition, the status
      of timing in Parkinson's disease remains uncertain. Data are reported from
      patients with mild to moderate Parkinson's disease (both on and off medication)
      and age- and IQ-matched controls on a range of stimulus timing tasks without
      counting. Tasks used were temporal generalization, bisection, threshold
      determination, verbal estimation, and a memory for duration task. Performance of
      patients was generally "normal" on all tasks, but significant differences from
      performance of controls were found on the memory for duration task. Among the
      "normal" effects noted were arithmetic mean bisection, asymmetric temporal
      generalization gradients, and subjective shortening on the memory for duration
      task. The results suggest (a) that some previous reports of timing "deficits" in
      Parkinson's patients were possibly due to the use of tasks requiring a timed
      manual response and (b) small differences between patients and controls may be
      found on tasks where two stimuli are presented on each trial, whether patients
      are on medication or off it.

PMID- 18329151
TI  - Acute and repeated dose oral toxicity of N-acetyl-l-aspartic acid in Sprague
      Dawley rats.
AB  - N-acetyl-l-aspartic acid (NAA) is a constituent of the mammalian central nervous
      system (CNS) that has been identified in a number of commonly consumed foods. The
      current study reports the outcome of acute and repeated dose oral toxicology
      studies conducted with NAA in Sprague-Dawley (SD) rats. No mortalities or
      evidence of adverse effects were observed in SD rats following acute oral
      administration of 2000mg/kg NAA. In a separate study, NAA was added to the diets
      of SD rats (n=10/sex group) at concentrations corresponding to daily doses of 10,
      100, or 1000mg/kg/day for 14 consecutive days and 100, 500, and 1000mg/kg/day for
      another 14 days. All rats survived until scheduled sacrifice and no differences
      in body weights, feed consumption values, or clinical signs were observed in any
      of the treatment groups. No biologically significant differences were observed in
      functional observational battery (FOB), motor activity evaluations,
      ophthalmologic examinations, hematology, coagulation, clinical chemistry, or
      organ weights of any of the NAA treatment groups. Further, no test substance
      related gross or microscopic changes were observed in NAA exposure groups. Based
      on these results, NAA was not considered acutely toxic following oral exposure to
      2000mg/kg and the no-observed-adverse-effect-level (NOAEL) for systemic toxicity
      from repeated dose dietary exposure to NAA is 1000mg/kg/day.

PMID- 18329152
TI  - Induction of premature senescence in human lung cancer by fungal immunomodulatory
      protein from Ganoderma tsugae.
AB  - Purified recombinant fungal immunomodulatory protein from Ganoderma tsugae (reFIP
      gts) has anti-telomerase effects in human lung adenocarcinoma A549 cells.
      However, how reFIP-gts affects cancer cell fates remains unclear. Here, we
      demonstrated that reFIP-gts-treated lung cancer cells are arrested at G1 phase by
      flow cytometry and possess morphological phenotype consistent with cellular
      senescence. The senescent nature of these cells was supported by positive
      staining for senescence-associated beta-galactosidase activity and increased
      lysosomal content in A549 and CaLu-1 lung cancer cells. Arrest of cells at G1
      appears to be the key means through which reFIP-gts induces premature cellular
      senescence in A549 cells. Finally, reFIP-gts- treated A549 cells grew more slowly
      and formed significantly fewer cell colonies in soft agar than untreated A549
      cells. In an in vivo mouse model, A549 cells treated with reFIP-gts grew
      significantly slower than cells treated with PBS alone, confirming that lung
      tumor can be inhibited by reFIP-gts. The use of reFIP-gts may be a powerful new
      strategy for chemoprevention and antineoplastic therapy.

PMID- 18329153
TI  - The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome
      P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby
      enhancing its own genotoxicity.
AB  - 3-Nitrobenzanthrone (3-NBA) is a carcinogen occurring in diesel exhaust and air
      pollution. Using the (32)P-postlabelling method, we found that 3-NBA and its
      human metabolite, 3-aminobenzanthrone (3-ABA), are activated to species forming
      DNA adducts by cytosols and/or microsomes isolated from rat lung, the target
      organ for 3-NBA carcinogenicity, and kidney. Each compound generated identical
      five DNA adducts. We have demonstrated the importance of pulmonary and renal
      NAD(P)H:quinone oxidoreductase (NQO1) to reduce 3-NBA to species that are further
      activated by N,O-acetyltransferases and sulfotransferases. Cytochrome P450 (CYP)
      1A1 is the essential enzyme for oxidative activation of 3-ABA in microsomes of
      both organs, while cyclooxygenase plays a minor role. 3-NBA was also investigated
      for its ability to induce NQO1 and CYP1A1 in lungs and kidneys, and for the
      influence of such induction on DNA adduct formation by 3-NBA and 3-ABA. When
      cytosols from rats treated i.p. with 40mg/kg bw of 3-NBA were incubated with 3
      NBA, DNA adduct formation was up to 2.1-fold higher than in incubations with
      cytosols from control animals. This increase corresponded to an increase in
      protein level and enzymatic activity of NQO1. Incubations of 3-ABA with
      microsomes of 3-NBA-treated rats led to up to a fivefold increase in DNA adduct
      formation relative to controls. The stimulation of DNA adduct formation
      correlated with the potential of 3-NBA to induce protein expression and activity
      of CYP1A1. These results demonstrate that 3-NBA is capable to induce NQO1 and
      CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and
      carcinogenic potential.

PMID- 18329154
TI  - Comprehensive evaluation for quality of prehospital CPR.

PMID- 18329156
TI  - Left ventricular muscular false tendon.

PMID- 18329157
TI  - Implementation of therapeutic hypothermia guidelines for post-cardiac arrest
      syndrome at a glacial pace: seeking guidance from the knowledge translation
      literature.
AB  - The 2005 International Liaison Committee on Resuscitation (ILCOR) Consensus on
      Science and Treatment Recommendations document represents the most extensive and
      rigorous systematic review of the resuscitation literature to date and included
      evidence-based recommendations for post-resuscitation care. A new recommendation
      for the induction of mild therapeutic hypothermia for comatose cardiac arrest
      survivors was included in this document. Accordingly, constituent national member
      associations of ILCOR, including the American Heart Association, incorporated the
      recommendation for therapeutic hypothermia into their respective guidelines.
      Despite these endorsements there is a concern that therapeutic hypothermia is not
      being used in practice. Data from a number of surveys in Europe and the United
      States suggest that rates of use among physicians may be as low as 30-40%.
      Despite the cost and effort associated with the production of these guidelines
      and the potential impact on patient care, current efforts in implementing the
      guideline have not achieved widespread success. This commentary explores the
      issue of underutilization of the American Heart Association guidelines for
      therapeutic hypothermia and looks to the knowledge translation literature to
      inform a new approach to implementation. We will review the underlying phenomenon
      of research implementation into practice, specific barriers to guideline
      implementation and interventions that may improve therapeutic hypothermia uptake.

PMID- 18329158
TI  - From agonal to output: an ECG history of a successful pre-hospital thoracotomy.

PMID- 18329159
TI  - A new paradigm for human resuscitation research using intelligent devices.
AB  - OBJECTIVES: To develop new methods for studying correlations between the
      performance and outcome of resuscitation efforts in real-world clinical settings
      using data recorded by automatic devices, such as automatic external
      defibrillators (AEDs), and to explore effects of shock timing and chest
      compression depth in the field. METHODS: In 695 records of AED use in the pre
      hospital setting, continuous compression data were recorded using AEDs capable of
      measuring sternal motion during compressions, together with timing of delivered
      shocks and the electrocardiogram. In patients who received at least one shock,
      putative return of spontaneous circulation (P-ROSC) was defined as a regular,
      narrow complex electrical rhythm > 40 beats/min with no evidence of chest
      compressions at the end of the recorded data stream. Transient return of
      spontaneous circulation (t-ROSC) was defined as the presence of a post-shock
      organized rhythm > 40 beats/min within 60s, and sustained > or = 30 s. 2x2
      contingency tables were constructed to examine the association between these
      outcomes and dichotomized time of shock delivery or chest compression depth,
      using the Mood median test for statistical significance. RESULTS: The probability
      of P-ROSC for first shocks delivered < 50 s (the median time) after the start of
      resuscitation was 23%, versus 11% for first shocks > 50 s (p=0.028, one tailed).
      Similarly, the probability of t-ROSC for shorter times to shock was 29%, compared
      to the 15% for delayed first shocks (p=0.016). For shocks occurring > 3 min after
      initiation of rescue attempts, the probability of t-ROSC with pre-shock average
      compression depth > 5 cm was more than double that with compression depth < 5 cm
      (17.7% vs. 8.3%, p=0.028). For shocks > 5 min, the effect of deeper compressions
      increased (23.4% versus 8.2%, p=0.008). CONCLUSIONS: Much can be learned from
      analysis of performance data automatically recorded by modern resuscitation
      devices. Use of the Mood median test of association proved to be sensitive,
      valid, distribution independent, noise-resistant and also resistant to biases
      introduced by the inclusion of hopeless cases. Efforts to shorten the time to
      delivery of the first shock and to encourage deeper chest compressions after the
      first shock are likely to improve resuscitation success. Such refinements can be
      effective even after an unknown period of preceding downtime.

PMID- 18329160
TI  - Amino acid network and its scoring application in protein-protein docking.
AB  - Protein-protein complex, composed of hydrophobic and hydrophilic residues, can be
      divided into hydrophobic and hydrophilic amino acid network structures
      respectively. In this paper, we are interested in analyzing these two different
      types of networks and find that these networks are of small-world properties. Due
      to the characteristic complementarity of the complex interfaces, protein-protein
      docking can be viewed as a particular network rewiring. These networks of correct
      docked complex conformations have much more increase of the degree values and
      decay of the clustering coefficients than those of the incorrect ones. Therefore,
      two scoring terms based on the network parameters are proposed, in which the
      geometric complementarity, hydrophobic-hydrophobic and polar-polar interactions
      are taken into account. Compared with a two-term energy function, a simple
      scoring function HPNet which includes the two network-based scoring terms shows
      advantages in two aspects, not relying on energy considerations and better
      discrimination. Furthermore, combing the network-based scoring terms with some
      other energy terms, a new multi-term scoring function HPNet-combine can also make
      some improvements to the scoring function of RosettaDock.

PMID- 18329161
TI  - Modulation of protein stability by O-glycosylation in a designed Gc-MAF analog.
AB  - The post-translational modification of proteins by the covalent attachment of
      carbohydrates to specific side chains, or glycosylation, is emerging as a crucial
      process in modulating the function of proteins. In particular, the dynamic
      processing of the oligosaccharide can correlate with a change in function. For
      example, a potent macrophage-activating factor, Gc-MAF, is obtained from serum
      vitamin D binding protein (VDBP) by stepwise processing of the oligosaccharide
      attached to Thr 420 to the core alpha-GalNAc moiety. In previous work we designed
      a miniprotein analog of Gc-MAF, MM1, by grafting the glycosylated loop of Gc-MAF
      on a stable scaffold. GalNAc-MM1 showed native-like activity on macrophages
      (Bogani 2006, J. Am. Chem. Soc. 128 7142-43). Here, we present data on the
      thermodynamic stability and conformational dynamics of the mono- and
      diglycosylated forms. We observed an unusual trend: each glycosylation event
      destabilized the protein by about 1 kcal/mol. This effect is matched by an
      increase in the mobility of the glycosylated forms, as evaluated by molecular
      dynamics simulations. An analysis of the solvent-accessible surface area shows
      that glycosylation causes the three-helix bundle to adopt conformations in which
      the hydrophobic residues are more solvent exposed. The number of hydrophobic
      contacts is also affected. These two factors, which are ultimately explained with
      a change in occupancy for conformers of specific side chains, may contribute to
      the observed destabilization.

PMID- 18329162
TI  - Simulation and validation of arterial ultrasound imaging and blood flow.
AB  - We reviewed the simulation and validation of arterial ultrasound imaging and
      blood flow assessment. The physical process of ultrasound imaging and measurement
      is complex, especially in disease. Simulation of physiological flow in a phantom
      with tissue equivalence of soft tissue, vessel wall and blood is now achievable.
      Outstanding issues are concerned with production of anatomical models, simulation
      of arterial disease, refinement of blood mimics to account for non-Newtonian
      behavior and validation of velocity measurements against an independent technique
      such as particle image velocimetry. String and belt phantoms offer simplicity of
      design, especially for evaluation of velocity estimators, and have a role as
      portable test objects. Electronic injection and vibrating test objects produce
      nonphysiologic Doppler signals, and their role is limited. Computational models
      of the ultrasound imaging and measurement process offer considerable flexibility
      in their ability to alter multiple parameters of both the propagation medium and
      ultrasound instrument. For these models, outstanding issues are concerned with
      the inclusion of different tissue types, multilayer arteries, inhomogeneous
      tissues and diseased tissues.

PMID- 18329163
TI  - Progressive spontaneous occlusion of a cerebellar AVM: pathogenetic hypothesis
      and review of literature.
AB  - Cerebral arteriovenous malformation (AVM) is a complex network of vascular
      channels consisting of arterial feeders, a nidus and enlarged venous drainage.
      AVMs usually increase in size with time, but may rarely obliterate; spontaneous
      angiographic regression occurs in less than 1.5% of cerebral AVMs. Several causes
      of spontaneous regression have been postulated such us hemodynamic alterations
      due to hemorrhage, hypercoagulability, atherosclerosis, and tromboembolism from
      associated aneurysms. In this report we describe a case of spontaneous, complete
      and asymptomatic occlusion of a left cerebellar hemispheric AVM; angiograms
      clearly demonstrate a progressive decrease in size of the AVM at follow-up.
      Thrombosis of the dominant-draining vein caused by turbulent blood flow seemed to
      be the main driver. Possible mechanisms leading to the occlusion are discussed
      and a review of the literature is reported.

PMID- 18329164
TI  - Bradycardia in neurosurgery.
AB  - Cushing reflex' is characterized by the occurrence of hypertension, bradycardia
      and apnoea secondary to raised increased intracranial pressure (ICP), leading to
      pressure on and or stretch, or both, of the brainstem. With the wide availability
      of monitoring facilities and advancements in investigation techniques,
      observation of increased intracranial pressure resulting in haemodynamic
      instability and bradycardia has been increasingly recognized in relation to many
      neurosurgical conditions and procedures. The causes of bradycardia include space
      occupying lesion involving or compressing the brain parenchyma (subdural
      haematoma, tumours, hydrocephalus), neurosurgical procedures (neuroendoscopy,
      placement of extradural drains), epileptic and non-epileptic seizures, trigemino
      cardiac reflex, cerebellar lesions, spinal lesions (neurogenic shock, autonomic
      dysreflexia) and many other rare causes (Ventricular catheter obstruction in
      cases of hydrocephalus, colloid cysts related acute neurogenic cardiac
      dysfunction, Ondine's curse syndrome, etc.). This highlights that bradycardia can
      be a warning sign in many neurosurgical conditions and Cushing's reflex is a
      protective and effective action of the brain for preserving an adequate cerebral
      perfusion pressure despite an increased intracranial pressure. Management of
      these patients include identification and treatment of the underlying cause of
      bradycardia, anti-cholinergics and if necessary cardiac pacing, nevertheless,
      other causes of haemodynamic changes (i.e. anesthetic drugs, tumor manipulation)
      should also be considered and managed accordingly. We believe that this knowledge
      and understanding will help to identify the patients' at risk and will also help
      in the management of neurosurgical patients with bradycardia.

PMID- 18329165
TI  - Odor abnormalities caused by bilateral thalamic infarction.
AB  - Odor is the only sensation thought to be unrelated to the thalamus. However,
      accumulating evidence suggests that the dorsomedial nucleus (DM) of the thalamus
      is associated with odor. Although the thalamus is prone to ischemia, only a
      single patient with bilateral DM infarctions was reported to have odor
      abnormalities. We describe a second such patient with infarctions involving the
      left DM and the right ventral posterior nucleus and ventral lateral nucleus,
      nuclei adjacent to the DM, associated with transient edema. In contrast to the
      previous case, our patient had transient odor abnormality. These observations
      suggested that direct and/or indirect bilateral involvement of the DM might be
      associated with odor abnormalities in patients with thalamic infarction.

PMID- 18329166
TI  - Effects of microbubbles on ultrasound-mediated gene transfer in human prostate
      cancer PC3 cells: comparison among Levovist, YM454, and MRX-815H.
AB  - We compared the enhancement effects of three different echo contrast agents
      (ECAs); Levovist, YM454, and MRX-815H as artificial microbubbles on ultrasound
      mediated gene transfection (USMGT) with 1MHz ultrasound at 0.2MPa using a
      luciferase expression vector in PC3 cells and elucidated the mechanisms of
      differences of USMGT facilitation by these ECAs. At a concentration of each ECA
      that induced iso-survival, ECAs with lipid shell (YM454 and MRX-815H) facilitated
      USMGT higher than those without shell (Levovist), and the order of the ECAs
      facilitating free radical formation by sonication was; YM454>MRX-815H>Levovist.
      These results suggested that the lipid shell type ECAs facilitated gene transfer
      higher than that by the non-shell type ECA.

PMID- 18329167
TI  - Dechlorination of atrazine using zero-valent iron (Fe0) under neutral pH
      conditions.
AB  - Zero-valent iron (Fe0) is frequently used for the dechlorination of pesticides,
      because it is economical, easily acquired and stable. The kinetics of
      dechlorination by Fe0 are improved at low pH, but this requires additional acid
      addition, while dechlorination hardly occurs under basic conditions. Due to the
      buffer capacity of geological materials such as clay and sediment, however, the
      addition of acid to obtain a low pH may not be effective. In this research, the
      dechlorination constants of atrazine by Fe0 were measured with the addition of
      buffer solution to simulate the buffer capacity of sediment. In the presence of
      the buffer solution, the pH values remained neutral, while dechlorination
      occurred more slowly than that observed under acid additions but faster than that
      without any buffer. When the initial concentrations of atrazine were 10mg/L, 30
      mg/L, and 50mg/L, its dechlorination was explained using pseudo-first order
      reaction kinetics. The pseudo-first order constants were 3.01 x 10(-2)d(-1) at 10
      mg/L, 3.23 x 10(-2)d(-1) at 30 mg/L and 3.38 x 10(-2)d(-1) at 50mg/L. In
      addition, the half-lives of atrazine were 8.91 d at 10mg/L, 9.32 d at 30 mg/L,
      and 10.00 d at 50mg/L. Acid addition may not be omitted to obtain acidic pH
      conditions when dechlorination is necessary in geologic materials.

PMID- 18329168
TI  - Simultaneous extraction and catalytic adsorptive stripping voltammetric
      measurement of Cr(VI) in solid samples.
AB  - A fast, simple, sensitive and economical method for Cr(VI) extraction and
      determination in solid samples was developed and evaluated. The presented
      protocol for Cr(VI) determination in solid samples allows for simultaneous
      extraction and determination of Cr(VI) in one step. The procedure is based on a
      quantitative extraction method in which the complexing properties of
      diethylenetriaminepentaacetic acid (DTPA) were exploited to extract total Cr(VI)
      (soluble and insoluble forms) from the solid sample. A catalytic adsorptive
      stripping voltammetric technique is employed for direct determination of Cr(VI)
      in the extract. The effects of analytical parameters such as temperature, pH,
      composition and concentration of the supporting electrolyte (which simultaneously
      plays the role of extractant), extraction and accumulation time were
      investigated. The accuracy of the proposed procedure was tested by analyzing
      certified reference materials CRM 013 Paint Chips and CRM 019 Ash. The results
      obtained were compared with the results obtained using two other reference
      extraction procedures. The effects of potentially interfering ions which
      generally accompany Cr(VI) in natural samples on the Cr(VI) determination, with
      special notice to Cr(III) interference, are reported.

PMID- 18329169
TI  - Optimization of basic dye removal by oil palm fibre-based activated carbon using
      response surface methodology.
AB  - Oil palm fibre was used to prepare activated carbon using physiochemical
      activation method which consisted of potassium hydroxide (KOH) treatment and
      carbon dioxide (CO(2)) gasification. The effects of three preparation variables:
      the activation temperature, activation time and chemical impregnation (KOH:char)
      ratio on methylene blue (MB) uptake from aqueous solutions and activated carbon
      yield were investigated. Based on the central composite design (CCD), a quadratic
      model and a two factor interaction (2FI) model were respectively developed to
      correlate the preparation variables to the MB uptake and carbon yield. From the
      analysis of variance (ANOVA), the significant factors on each experimental design
      response were identified. The optimum activated carbon prepared from oil palm
      fibre was obtained by using activation temperature of 862 degrees C, activation
      time of 1h and chemical impregnation ratio of 3.1. The optimum activated carbon
      showed MB uptake of 203.83 mg/g and activated carbon yield of 16.50%. The
      equilibrium data for adsorption of MB on the optimum activated carbon were well
      represented by the Langmuir isotherm, giving maximum monolayer adsorption
      capacity as high as 400mg/g at 30 degrees C.

PMID- 18329170
TI  - Influence of the wastewater composition on denitrification and biological p
      removal in the S-DN-P-process (b) Effect of acetate.
AB  - The effect of acetate was examined during the p-removal and denitrification of
      wastewater. The plant was operated based on the sequencing-batch-biofilm-reactor
      (SBBR) process. As microbial media, ca. 9 mm Bio-Flow granules made from
      polyethylene and polypropylene were used. Three preparations were made to compare
      the level of biological p-removal and denitrification. In comparison to the batch
      test, 42 mg/L (AC 30) and 84 mg/L (AC 60) of NaCH(3)COO were mixed with the 500
      mL of raw wastewater and the effect of the acetate concentration on the level of
      p-removal was monitored. All samples were immediately filtered with 0.45 microm
      membrane filter, and PO(4)-P, NO(3)-N, NO(2)-N and acetate were analyzed using
      Ion Chromatography, whereas P(total) and chemical oxygen demand (COD) were
      measured by a spectrophotometer. The p-removals for the WW, WW+AC 30 and WW+AC 60
      preparations were found to be 9.4, 9.1 and 13.1mg/L, respectively. The WW+AC 30
      preparation did not show any significant effect on the p-removal, while p-removal
      in WW+AC 60 preparation was higher than that in the other two preparations. A
      comparison of the data revealed the COD: NO(3)-N:AC:P ratio of the WW, WW+AC 30
      and WW+AC 60 preparations to be 18.07:2.90:6.87:1, 21.28:2.45:5.98:1 and
      15.95:2.75:6.18:1, respectively. The experimental results showed that
      approximately 7 mg/L of acetate was consumed per 1mg/L of p-removal.

PMID- 18329171
TI  - NF-kB/NOS cross-talk induced by mitochondrial complex II inhibition: implications
      for Huntington's disease.
AB  - Nuclear factor-kB (NF-kB) is a family of DNA-binding proteins that are important
      regulators involved in immune and inflammatory responses, as well as in cell
      survival and apoptosis. In the nervous system NF-kB is activated under
      physiological and pathological conditions including learning and memory
      mechanisms and neurodegenerative diseases. NF-kB is activated in neurons in
      response to excitotoxic, metabolic and oxidative stress and there is a body of
      evidence to suggest that glutamate induces NF-kB by the main ionotropic glutamate
      receptors. In the present study, 3 nitroproprionic acid (3NP), an irreversible
      inhibitor of succinate dehydrogenase (SD, complex II) has been employed to
      provide an experimental model of Huntington's disease (HD). Specifically, we
      described 3NP-induced activation of NF-kB and of iNOS and nNOS genes in striatal
      treated slices. To aim to better understand the relationship between these
      identified dysregulated genes and mitochondrial dysfunction, we investigated in
      SK-N-MC human neuroblastoma cells following 3NP treatment, whether NF-kB nuclear
      translocation and activation might be involved in the mechanisms by which 3NP
      leads to transcriptional activation of NOS genes. These results are relevant to
      more precisely define the role of NF-kB in neuronal cells and better understand
      its putative involvement in neurodegeneration.

PMID- 18329172
TI  - Lipopolysaccharide activates the kallikrein-kinin system in mouse choroid plexus
      cell line ECPC4.
AB  - Regulation of the kallikrein-kinin system in cerebral inflammation is still
      unclear. Here, we used reverse-transcription polymerase chain reaction (RT-PCR)
      techniques to show that lipopolysaccharide (LPS) activates the kallikrein-kinin
      system by enhancing liberation of bradykinin (BK), and alters mRNA levels of
      kallikrein-kinin system components, including high molecular weight (H-) and low
      molecular weight (L-) kininogens, in ECPC4 cells, a cell line of mouse choroid
      plexus epithelium. LPS treatment increased liberation of immunoreactive
      bradykinin in the supernatant of ECPC4 cells, and addition of LPS (500 ng/ml) to
      cultures resulted in elevation of H- and L-kininogen mRNA levels in ECPC4 cells
      within 24-48 h. Furthermore, LPS treatment elevated bradykinin type 2 and type 1
      receptor mRNA levels within 4h, but did not change tissue kallikrein or plasma
      kallikrein mRNA levels. On the other hand, expression of pro-inflammatory
      mediators interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha),
      and cyclooxygenase-2 mRNA increased within 4-8h after addition of LPS to ECPC4
      cells. The addition of IL-1beta and TNF-alpha to investigate the major mediator
      for kininogen expression in ECPC4 cells remarkably induced expression of H- and L
      kininogen mRNAs in ECPC4 cells. These results suggest that LPS activates the
      kallikrein-kinin system in the choroid plexus via autocrine induction of IL-1beta
      and TNF-alpha.

PMID- 18329173
TI  - Accuracy and precision in model based EELS quantification.
AB  - We present results on model based quantification of electron energy loss spectra
      (EELS), focusing on the factors that influence accuracy and precision in
      determining chemical concentrations. Several sources of systematical errors are
      investigated. The spectrometer entrance aperture determines the collection angle,
      and the effects of its position with respect to the transmitted beam are
      investigated, taking into account the diffraction by the crystal structure. The
      effect of the orientation of the sample is tested experimentally and
      theoretically on SrTiO3, and finally, a simulated experiment on c-BN at different
      thicknesses confirms the superior results of the model based method with respect
      to the conventional method. A test on a set of experimental reference compounds
      is presented, showing that remarkably good accuracy can be obtained.
      Recommendations are given to achieve high accuracy and precision in practice.

PMID- 18329174
TI  - Toxoplasma gondii infection in Blanford's fox (Vulpes cana).
AB  - Fatal toxoplasmosis was diagnosed in a Blanford's fox (Vulpes cana) from the
      United Arab Emirates. Toxoplasma gondii-like tachyzoites were found associated
      with necrosis in intestine, spleen, liver, kidneys, lungs, skeletal muscle, brain
      and heart. Protozoal tachyzoites reacted positively with T. gondii-specific
      polyclonal antibodies. Antibodies to T. gondii were detected in 10 of 12 V. cana
      assayed by the latex agglutination or the modified direct agglutination test.

PMID- 18329175
TI  - The ecology of horse cyathostomin infective larvae (Nematoda-Cyathostominae) in
      tropical southeast Brazil.
AB  - Experimental studies about the recovery, survival and migration to pasture of
      cyathostomin infective larvae (L(3)) from fresh feces depositions were conducted
      from February 2005 to March 2007 in a tropical region of southeast Brazil. Grass
      and feces were collected weekly at 8 a.m., 1 and 5 p.m. and processed by the
      Baermann technique. Multivariate analysis (principal components method) showed
      the influence of time and environmental variables on the number of infective
      larvae recovered from the feces and pasture. In the rainy period (October-March),
      more infective larvae were recovered on the feces and grass apex. In contrast, in
      the dry period (April-September), the recovery was higher only on the grass base,
      as well as the L(3) survival on feces and grass. More larvae were recovered at 8
      a.m., except from the grass apex, where the highest recovery was at 1 p.m. Few
      studies investigating the seasonal transmission of equine cyathostomin have been
      conducted in South American tropical climates. These results demonstrate that in
      tropical conditions L(3) are available on feces and pasture throughout the year.
      Knowledge of climatic influences on the development and survival of L(3) is
      crucial to designing integrated parasite control programs that provide effective
      protection while slowing the development of anthelmintic resistance.

PMID- 18329176
TI  - Synapses are lost during aging in the primate prefrontal cortex.
AB  - An electron microscopic analysis has been carried out on the effects of age on
      the numerical density of both excitatory (asymmetric) and inhibitory (symmetric)
      synapses in the neuropil of layers 2/3 and of layer 5 in area 46 from the frontal
      cortex of behaviorally tested rhesus monkeys. There is no change in the lengths
      of synaptic junctions with age or in the percentage distribution of synapses
      relative to the postsynaptic spines and dendritic shafts. However, in layers 2/3
      there is an overall loss of about 30% of synapses from 5 to 30 years of age, and
      both asymmetric and symmetric synapses are lost at the same rate. In layer 5 the
      situation is different; the overall loss of synapses is only 20% and this is
      almost entirely due to a loss of asymmetric synapses, since there is no
      significant loss of symmetric synapses from this layer with age. When the synapse
      data are correlated with the overall cognitive impairment shown by the monkeys,
      it is found that there is a strong correlation between the numerical density of
      asymmetric synapses in layers 2/3 and cognitive impairment, with a weaker
      correlation between symmetric synapse loss and cognitive impairment. In layer 5
      on the other hand there is no correlation between synapse loss and cognitive
      impairment. However synapse loss is not the only factor causing cognitive
      impairment, since in previous studies of area 46 we have found that age-related
      alteration in myelin in this frontal area also significantly contributes to
      cognitive decline. The synapse loss is also considered in light of earlier
      studies, which show that the frequency of spontaneous excitatory synaptic
      responses is reduced with age in layers 2/3 neurons.

PMID- 18329177
TI  - Characterization of the hypothalamic proopiomelanocortin gene and beta-endorphin
      expression in the hypothalamic arcuate nucleus of mice elicited by inflammatory
      pain.
AB  - We examined proopiomelanocortin (POMC) mRNA and beta-endorphin expression in the
      hypothalamus of mice after various nociceptive stimuli. The time-course study (10
      min, 30 min, 1 h, 2 h, and 10 h) showed that the POMC mRNA level significantly
      increases from 1 h after s.c. formalin injection and returns to the control level
      at 10 h. Intrathecal (i.t.) substance P (SP) injection also increases the
      hypothalamic POMC mRNA level from 1 h to 10 h. However, i.t. glutamate injection
      did not affect the hypothalamic POMC gene expression at all time points. We found
      that the POMC mRNA after s.c. formalin injection was located in the arcuate
      nucleus of the hypothalamus. In the same manner, beta-endorphin immunoreactivity
      was also increased in the hypothalamic arcuate nucleus. The expression of
      phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2),
      phosphorylated calcium/calmodulin-dependent protein kinase-IIalpha (pCaMK
      IIalpha) protein and phosphorylated IkappaB (pIkappaB) protein was increased by
      s.c. formalin injection at various time points. We also found that increased
      pERK1/2, pCaMKIIalpha and pIkappaB protein after s.c. formalin injection was
      mainly located in the arcuate nucleus of hypothalamus in which cells containing
      beta-endorphin after s.c. formalin injection also express pERK1/2, pCaMK-IIalpha
      and pIkappaB immunoreactivity. In addition, formalin-induced POMC mRNA expression
      was significantly reduced by 10 min, pretreatment with i.c.v. PD98059 (mitogen
      activated protein kinase (MAPK) pathways inhibitor; 6.6 mug) and KN93 (pCaMK-II
      inhibitor; 20 mug). In conclusion, POMC mRNA expression in the arcuate nucleus of
      the hypothalamus was increased by inflammatory pain stimuli, in which pERK1/2,
      pCaMK-IIalpha and NFkappaB may play an important role in the expression of the
      hypothalamic POMC gene and beta-endorphin expression.

PMID- 18329178
TI  - Modulation of pentylenetetrazol-induced seizures by prostaglandin E2 receptors.
AB  - There is evidence that prostaglandin E2 (PGE2) facilitates the seizures induced
      by pentylenetetrazol (PTZ), but the role of PGE2 receptors (EPs) in the
      development of seizures has not been evaluated to date. In the current study we
      investigated whether selective EP ligands alter PTZ-induced seizures in adult
      male Wistar rats by electrographic methods. Selective antagonists for EP1 (SC
      19220, 10 nmol, i.c.v.), EP3 (L-826266, 1 nmol, i.c.v.) and EP4 (L-161982, 750
      pmol, i.c.v.) receptors, and the selective EP2 agonist butaprost (100 pmol,
      i.c.v.) increased the latency for clonic and generalized tonic-clonic seizures
      induced by PTZ. These data constitute pharmacological evidence supporting a role
      for EPs in the seizures induced by PTZ. Although more studies are necessary to
      fully evaluate the anticonvulsant role these compounds and their use in the
      clinics, EP ligands may represent new targets for drug development for convulsive
      disorders.

PMID- 18329179
TI  - Patients with adverse mood effects from combined oral contraceptives have lower
      levels of prepulse inhibition than healthy controls.
AB  - BACKGROUND: Negative mood symptoms remain one of the major reasons for
      discontinuation of oral contraceptive pills. The aim of this study was to compare
      acoustic startle response and prepulse inhibition (PPI) in women with different
      experience of oral contraceptive pills. METHODS: Thirty women currently on
      combined oral contraceptives (COCs) with no reports of adverse mood symptoms, 28
      women currently on COCs and experiencing mood-related side effects from
      treatment, 27 women who had discontinued COC use for reasons other than adverse
      mood symptoms and 32 women who had discontinued COC use due to adverse mood
      effects were included. The eyeblink component of the acoustic startle reflex was
      assessed using electromyographic measurements of musculus Orbicularis Oculi.
      Twenty pulse-alone trials (115dB 40ms broad-band white noise) and 40 prepulse
      pulse trials were presented. The prepulse stimuli consisted of a 115dB 40ms noise
      burst preceded at a 100ms interval by 20ms prepulses that were 72, 74, 78, or
      86dB. RESULTS: Patients with adverse mood effects of COCs exhibited lower levels
      of PPI with 86dB prepulse compared to COC users with no adverse effects of COCs
      (p<0.05). There was no difference in PPI between the two groups of prior COC
      users. No significant difference was found between the groups regarding acoustic
      startle response. CONCLUSION: Relative to COC users with no reports of adverse
      mood symptoms, subjects suffering from COC-induced negative mood displayed
      deficits in PPI of acoustic startle. The fact that there was no difference in PPI
      between the two groups of prior COC users indicates that deficient PPI is related
      to adverse mood effects caused by COCs.

PMID- 18329180
TI  - HPA system regulation and adult attachment anxiety: individual differences in
      reactive and awakening cortisol.
AB  - Early life experiences can influence hypothalamus-pituitary-adrenal (HPA) axis
      regulation in adulthood, in both animals and humans. In humans, they have also
      been shown to influence adult attachment styles. However, the relationship
      between adult attachment styles and HPA axis regulation is largely unexplored.
      The present study investigated the relationship among varying levels of
      attachment anxiety and avoidance with both the cortisol response to acute stress
      (CRS) and the cortisol response to awakening (CRA) in 48 adult women. Attachment
      unrelated stress was induced by a laboratory stress task. Saliva for free
      cortisol assessment was sampled before and after the stress task in the
      laboratory and at home on 2 consecutive days in the morning after awakening. We
      found that attachment anxiety but not attachment avoidance was associated with
      cortisol measures. Attachment anxiety was positively correlated with CRS and
      negatively with CRA. Finally, the two cortisol parameters were negatively
      associated with one another. The results are discussed with respect to (1) recent
      findings suggesting that the HPA system and hippocampus are programmed during
      critical development periods, establishing a certain trajectory of physiological
      responsiveness throughout life, and (2) a model that links development of the
      hippocampus with self development.

PMID- 18329181
TI  - Rejection sensitivity relates to hypocortisolism and depressed mood state in
      young women.
AB  - Rejection sensitivity and the associated fear of negative social evaluation
      (FNSE) trait are characteristics of hypocortisolemic syndromes such as atypical
      depression. However, a meta-analysis showed that acute FNSE evokes strong
      cortisol responses in humans. This is consistent with suggestions that
      hypocortisolism reflects a protective adaptation to a history of high cortisol
      responses. This leads us to hypothesize that measures of trait FNSE relate to
      hypocortisolism. Moreover, because FNSE relates positively to depressed mood
      state, but negatively to cortisol, we expect that the positive relationship
      between depressed mood state and cortisol will show up most clearly when
      controlling for the confounding effect of FNSE on this relationship. In the
      present study we measured salivary cortisol awakening response and psychological
      variables in 194 community women aged 18-30 years. The results confirmed our
      hypotheses. We propose that dispositional FNSE is associated with a history of
      frequent high cortisol responses, leading to long-term protective inhibition of
      further cortisol and energy mobilization. The present results have special
      relevance for mental health problems that have high prevalence among young women.

PMID- 18329182
TI  - Psychological coping styles and cortisol over the day in healthy older adults.
AB  - Patterns of psychological coping are associated with a variety of health outcomes
      but the underlying pathways are not yet established. The purpose of this study
      was to assess the relationship between salivary cortisol output over the course
      of a day and coping style. Data were available from 350 men and 192 women with an
      average age of 60.9 years. Participants were drawn from the Whitehall II cohort,
      and had no history of cardiovascular disease. Individuals who were taking
      medication that might affect cortisol levels were also excluded. Saliva samples
      were provided on waking, then 0.5, 2.5, 8 and 12h after waking, and just before
      the participant went to sleep. Coping style was measured with a standard
      instrument, the COPE, and data were factor analysed to generate three factors:
      seeking social support, problem engagement and problem avoidance. The
      relationships between these factors and the cortisol awakening response (CAR),
      the slope of cortisol change over the day and total cortisol output over the day
      (excluding the waking period) were assessed using multiple linear regression.
      Cortisol output over the day was inversely associated with coping with stress by
      seeking social support (p=0.034) and by problem engagement (p=0.003),
      independently of age, gender, body mass index, smoking, depression, self-rated
      health, time of waking and income. Individuals who coped by problem engagement
      and seeking support had lower cortisol levels. Additionally, gender, BMI,
      smoking, self-rated health and time of waking were independently related to
      cortisol output over the day. There were no significant associations between
      coping and the CAR or cortisol slope over the day. The results indicate that
      adaptive coping styles are related to low levels of cortisol over the day,
      suggesting that neuroendocrine pathways may partly mediate relationships between
      psychological coping and health.

PMID- 18329183
TI  - Transforming growth factor-beta1: a possible risk stratification tool for atrial
      fibrillation.

PMID- 18329184
TI  - Increased availability of estrogens to the foetus and the risk of testicular
      cancer in later life: does insulin have a role?

PMID- 18329185
TI  - Antioxidant activity of banana flavonoids.
AB  - The antioxidant activity of flavonoids from banana (Musa paradisiaca) was studied
      in rats fed normal as well as high fat diets. Concentrations of peroxidation
      products namely malondialdehyde, hydroperoxides and conjugated diens were
      significantly decreased whereas the activities of catalase and superoxide
      dismutase were enhanced significantly. Concentrations of glutathione were also
      elevated in the treated animals.

PMID- 18329186
TI  - [Prevention and early management of immediate postpartum haemorrhage: policies in
      six perinatal networks in France].
AB  - OBJECTIVES: Postpartum haemorrhage (PPH) constitutes the leading cause of
      maternal deaths in France, and the majority of these deaths are preventable. The
      objective of this study was to ascertain policies for prevention and early
      management of PPH in maternity units, and to compare the results with scientific
      evidence. The survey was part of the Euphrates European project, and was
      conducted in France in 2003 before national recommendations for clinical practice
      related to PPH were launched. MATERIALS AND METHODS: A cross-sectional
      declarative survey was conducted in six perinatal networks representing 132
      maternity units. A postal questionnaire was sent to all units. Main outcomes
      measured were stated policies for prevention, diagnosis and management of PPH.
      RESULTS: There was no definition of PPH in one out of four units, and no written
      protocol for PPH management in one out of six. Policies of using preventive
      uterotonics were widespread, but variation was observed concerning the timing of
      administration, and association with the other components of active management of
      the third stage of labour. Policies about drugs used for management of PPH also
      varied. CONCLUSION: Variations in policies show firstly that evidence-based
      improvement in practice is possible, and secondly that further research is needed
      on poorly documented aspects of PPH management.

PMID- 18329187
TI  - Behavioral contingency analysis.
AB  - This paper presents a formal symbolic language, with its own specialized
      vocabulary and grammar, for codifying any behavioral contingency, including the
      complex multiparty contingencies encountered in law, economics, business, public
      affairs, sociology, education, and psychotherapy. This language specifies the
      "if, then" and temporal relationships between acts and their consequences for the
      parties involved. It provides for the notation of the probabilities, magnitudes,
      positive or negative valences, or time delays of the consequences for the
      parties, and for the parties that would perceive, misperceive, not perceive,
      predict, mispredict, or not predict events. The language's fractal-like
      hierarchical and recursive grammar provides for the flexible combination and
      permutation of the modifiers of the language's four nouns: acts, consequences,
      time intervals, and agents of acts; and its four verbs: consequate, prevent,
      perceive, and predict-thereby giving the language the ability to describe and
      codify various nuances of such complex contingencies as fraud, betting,
      blackmail, various types of games, theft, crime and punishment, contracts, family
      dynamics, racing, competition, mutual deterrence, feuding, bargaining, deception,
      borrowing, insurance, elections, global warming, tipping for service, vigilance,
      sexual overtures, decision making, and mistaken identity. Applications to the
      management of practical situations and techniques for doing so, as well as
      applications in current behavior analysis research and neuroscience, are
      discussed.

PMID- 18329188
TI  - Cognitive deficits in marijuana users: Effects on motivational enhancement
      therapy plus cognitive behavioral therapy treatment outcome.
AB  - Clinical variables that affect treatment outcome for marijuana-dependent
      individuals are not yet well understood, including the effects of cognitive
      functioning. To address this, level of cognitive functioning and treatment
      outcome were investigated. Twenty marijuana-dependent outpatients were
      administered a neuropsychological battery at treatment entry. All patients
      received 12 weekly individual sessions of combined motivational enhancement
      therapy and cognitive behavioral therapy. The Wilcoxon Exact Test was used to
      compare cognitive functioning test scores between completers and dropouts, and
      the Fisher Exact Test was used to compare proportion of negative urines between
      those with higher and lower scores on the cognitive tests. Marijuana abstinence
      was unrelated to cognitive functioning. However, dropouts scored significantly
      lower than completers on measures of abstract reasoning and processing accuracy,
      providing initial evidence that cognitive functioning plays a role in treatment
      retention of adult marijuana-dependent patients. If supported by further studies,
      the findings may help inform the development of interventions tailored for
      cognitively impaired marijuana-dependent patients.

PMID- 18329189
TI  - The impact of two universal randomized first- and second-grade classroom
      interventions on young adult suicide ideation and attempts.
AB  - OBJECTIVE: This paper reports the impact of two first- and second-grade classroom
      based universal preventive interventions on the risk of Suicide Ideation (SI) and
      Suicide Attempts (SA) by young adulthood. The Good Behavior Game (GBG) was
      directed at socializing children for the student role and reducing aggressive,
      disruptive behavior. Mastery Learning (ML) was aimed at improving academic
      achievement. Both were implemented by the teacher. METHODS: The design was
      epidemiologically based, with randomization at the school and classroom levels
      and balancing of children across classrooms. The trial involved a cohort of first
      grade children in 19 schools and 41 classrooms with intervention at first and
      second grades. A replication was implemented with the next cohort of first grade
      children with the same teachers but with little mentoring or monitoring. RESULTS:
      In the first cohort, there was consistent and robust GBG-associated reduction of
      risk for suicide ideation by age 19-21 years compared to youths in standard
      setting (control) classrooms regardless of any type of covariate adjustment. A
      GBG-associated reduced risk for suicide attempt was found, though in some
      covariate-adjusted models the effect was not statistically robust. No
      statistically significant impact on these outcomes was found for ML. The impact
      of the GBG on suicide ideation and attempts was greatly reduced in the
      replication trial involving the second cohort. CONCLUSIONS: A universal
      preventive intervention directed at socializing children and classroom behavior
      management to reduce aggressive, disruptive behavior may delay or prevent onset
      of suicide ideation and attempts. The GBG must be implemented with precision and
      continuing support of teachers.

PMID- 18329190
TI  - Quickly evolving histones, nucleosome stability and chromatin folding: all about
      histone H2A.Bbd.
AB  - Histone H2A.Bbd (Barr body-deficient) is a novel histone variant which is largely
      excluded from the inactive X chromosome of mammals. Discovered only 6 years ago,
      H2A.Bbd displays very unusual structural and functional properties, for instance,
      it is relatively shorter and only 48% identical compared to H2A, lacking both the
      typical C-terminal tail of the H2A family and the very last sequence of the
      docking domain, making it the most specialized among all histone variants known
      to date. Indeed, molecular evolutionary analyses have shown that H2A.Bbd is a
      highly hypervariable and quickly evolving protein exclusive to mammalian
      lineages, in striking contrast to all other histones. Different studies have
      described a deposition pattern of H2A.Bbd in the chromatin that overlaps with
      regions of histone H4 acetylation suggesting its association with
      transcriptionally active euchromatic regions of the genome. In this regard, it is
      believed that this histone variant plays an important role in determining such
      regions by destabilizing the nucleosome and locally unfolding the chromatin
      fiber. This review provides a concise, comprehensive and timely summary of the
      work published on H2A.Bbd structure and function. Special emphasis is placed on
      its chromatin deposition patterns in relation to gene expression profiles and its
      evolutionary history, as well as on the dynamics of H2A.Bbd-containing
      nucleosomes.

PMID- 18329191
TI  - Transcriptional regulation of the human CD97 promoter by Sp1/Sp3 in smooth muscle
      cells.
AB  - The EGF-TM7 receptor CD97 shows different features of expression and function in
      muscle cells compared to hematopoetic and tumor cells. Since the molecular
      function and regulation of CD97 are poorly understood, this study aimed at
      defining its basal transcriptional regulation in smooth muscle cells (SMCs). The
      computational analysis of the CD97 5'-flanking region revealed that the TATA box
      lacking promoter possesses several GC-rich regions as putative Sp1/Sp3 binding
      sites. Transfection studies with serially deleted promoter constructs
      demonstrated that the minimal promoter fragment resided in the -218/+45 region
      containing one out of five identified GC-boxes in the leiomyosarcoma cell line SK
      LMS-1 and human bronchial smooth muscle cells (HbSMCs). Mutation of the most
      proximal GC-site in CD97 reporter gene constructs caused a significant decrease
      in promoter activity. Gel shift assays and chromatin immunoprecipitation revealed
      that Sp1 and Sp3 bound specifically to the most proximal GC-site. Furthermore, we
      showed that Sp1 and Sp3 over-expression activates CD97 promoter activity in
      HEK293 cells. Our data characterize for the first time the activity of the human
      CD97 promoter which is controlled by Sp1/Sp3 transcription factors in SMCs.

PMID- 18329192
TI  - Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in skin lesions from dioxin
      exposed humans with chloracne.
AB  - Occupational exposure to certain polychlorinated aromatic hydrocarbons such as
      dioxins has been suggested to cause chloracne which is a kind of skin disease.
      The molecular mechanisms of dioxin-mediated chloracne have not been clarified. It
      is possible that dioxins contribute to the pathogenesis through activation of
      aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such
      as CYP1A1, GSTA1 and TGF-alpha. The study on genes was through chloracne lesional
      skin, which has rarely been reported on previously. The expression levels of key
      genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in human epidermal tissue
      of chloracne cases and controls were detected by real-time PCR. Compared with
      controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly
      induced in the skins of chloracne patients who had long-term exposure to dioxins
      and dibenzofuranes. The TGF-alpha mRNA content of epidermal tissue was increased,
      but not significantly compared with controls. The study demonstrates that
      constitutive activation of the AhR pathway is probably a prerequisite of
      chloracne pathogenesis. The changes of genes expression may disturb normal
      proliferation and differentiation of human epidermis cells, and then lead to
      chloracne.

PMID- 18329193
TI  - Ingestion of deoxynivalenol (DON) contaminated feed alters the pig vaccinal
      immune responses.
AB  - Deoxynivalenol (DON), a mycotoxin produced by some Fusarium species, is a
      frequent contaminant of cereals. This toxin is known to modulate the immune
      function but only few studies have investigated the effect of DON on the vaccinal
      immune response. In the present experiment, 24 pigs received for 9 weeks either
      control feed or feed naturally contaminated with 2.2-2.5 mgDON/kg feed. At days 4
      and 15 of the experiment, the animals were subcutaneously immunized with
      ovalbumin. Consumption of DON-contaminated diet does not have a major effect on
      the hematological and biochemical blood parameters. By contrast, ingestion of DON
      significantly affects the global and the specific immune response of the pigs. In
      the serum, DON increases the concentration of total IgA and, in vaccinated
      animals, DON also increases the concentration of ovalbumin-specific IgA and IgG.
      DON does not modulate lymphocytes proliferation after mitogenic stimulation but
      the toxin had a biphasic effect on lymphocyte proliferation after antigenic
      stimulation (up-regulation at day 21 and down-regulation at day 35-49). Because
      cytokines play a key role in immunity, the expression levels of TGF-beta, IFN
      gamma, IL-4 and IL-6 were measured, by RT-PCR in the spleen, the ileum and the
      mesenteric lymph node of the animals at the end of the experiment. In the
      mesenteric lymph node, a significantly lower expression of both TGF-beta and IFN
      gamma mRNA expression levels is observed in animals feed with DON when compared
      with control piglets. Taken together, our data indicate that DON alters the
      vaccinal immune response. These results may have implications for humans and
      animals consuming DON-contaminated food or feed as breakdown in vaccinal immunity
      may lead to the occurrence of disease even in properly vaccinated populations.

PMID- 18329194
TI  - Lyophilized Cheliensisin A submicron emulsion for intravenous injection:
      characterization, in vitro and in vivo antitumor effect.
AB  - Growing attentions have been focused on natural antitumor drugs. Recently, a
      novel and potent antitumor drug Cheliensisin A (GC-51) with broad-spectrum
      efficiency has been developed. However, due to its poor water solubility and
      chemical instability, choosing the appropriate dosage form is of great
      significance. This study aimed at developing a lyophilized submicron emulsion for
      GC-51 and further improving the therapeutic index of the drug. The resultant
      lyophilized GC-51 submicron emulsion was much more stable than its solution,
      which can be stored for years without significant change on physicochemical
      properties. And its solubility was increased from 6.74+/-0.14 to 2.00+/-0.10 mg
      mL(-1). The 50% inhibitory concentration IC50 values were calculated from growth
      curves by MTT assay on various tumor cell lines. Compared with the IC50 of GC-51
      crude drug, that of lyophilized GC-51 submicron emulsion decreased from 24.04+/
      1.97 to 8.23+/-1.84 microg mL(-1) on HepG2, and from 31.08+/-2.56 to 10.85+/-2.09
      microg mL(-1) on CT-26, from 17.90+/-1.83 to 7.49+/-1.87 microg mL(-1) on HeLa
      and from 16.38+/-2.41 to 10.13+/-2.12 microg mL(-1) on A549, respectively. In the
      time-dependent assay of tumor cell viability, lyophilized GC-51 submicron
      emulsion exhibited significantly lower inhibition rate in the initial action
      times, but increased gradually afterwards. That means lyophilized submicron
      emulsion as the vector for GC-51 had some protective and delayed release effect.
      Further, the in vivo therapeutic efficacy was measured in pulmonary metastasis of
      colon cancer-bearing BALB/c mice model. An obvious enhanced antitumor activity
      was observed after administration of lyophilized GC-51 submicron emulsion
      (P<0.05), which increased from 22.78+/-3.5 to 41.42+/-4.2% compared with GC-51
      injection. And the life span of tumor-bearing mice in lyophilized GC-51 submicron
      emulsion group was significantly longer than that of the mice in GC-51 injection
      and normal saline groups. Compared with crude drug, the lyophilized GC-51
      submicron emulsion showed a significantly higher antitumor efficiency both in
      vivo and in vitro, suggesting a potential application in tumor chemotherapy.

PMID- 18329195
TI  - Block copolymer design for stable encapsulation of N-(4-hydroxyphenyl)retinamide
      into polymeric micelles in mice.
AB  - For stable encapsulation of N-(4-hydroxyphenyl)retinamide (4-HPR) into polymeric
      micelles, four types of block copolymers were synthesized with different
      esterified functional groups: heptyl (C7), nonyl (C9), benzyl (Bz), and
      phenylpropyl (C3Ph). The stability of 4-HPR encapsulated polymeric micelles was
      evaluated by measuring the blood concentration of 4-HPR in mice. After
      intravenous administration of 4-HPR and 4-HPR encapsulated PEG liposomes, the
      blood concentration of 4-HPR was about 2.8% and 2.2% of the dose/mL, suggesting
      the rapid release of 4-HPR from PEG liposomes. In contrast, the blood
      concentration of 4-HPR after intravenous administration of all 4-HPR encapsulated
      polymeric micelles studied was much higher (about 22-34% of the dose/mL). Among
      them, the polymeric micelles prepared by block copolymers (Bz) showed the highest
      blood concentration of 4-HPR. As far as the effects of the level of Bz groups in
      the block copolymers are concerned, the blood concentration of 4-HPR was enhanced
      by Bz groups at a level of 72% and 77%, but not by Bz groups at a level of 43%
      and 51%. These results suggest that 4-HPR is stably encapsulated in polymeric
      micelles prepared by block copolymers (Bz) but a level of over 72% of Bz groups
      is needed. These findings will be of value in the future use, design, and
      development of polymeric micelles for in vivo application of 4-HPR.

PMID- 18329196
TI  - In situ fiber optic method for long-term in vitro release testing of
      microspheres.
AB  - The objective of this study was to develop an in vitro release method for
      relatively unstable drugs in long-term modified release (MR) formulations, such
      as microspheres. Drug stability in the release medium can complicate in vitro
      release testing of such delivery systems. To overcome this problem, a method has
      been developed where the model drug, cefazolin, and its degradation products are
      monitored simultaneously, using UV fiber optic probes, to account for cumulative
      drug release from poly(lactic-co-glycolic) acid (PLGA) microspheres. United
      States Pharmacopeia (USP) Apparatus 2 and 4 were used to evaluate cefazolin
      release throughout the 30-day study period. Cefazolin exhibits an isosbestic
      point (wavelength where the drug and the degradation products have the same
      absorbance). Cumulative drug release was compared at the isosbestic (288 nm)
      point and at the UV max (270 nm). Monitoring at the isosbestic point allowed
      determination of total drug release with approximately 100% release by day 25.
      Whereas, at the UV max approximately 61% release was detected by day 25 as a
      result of drug degradation. Problems were encountered using USP Apparatus 2 with
      the in situ UV fiber optic probes as a result of microsphere accumulation at and
      interference with the probe detection window.

PMID- 18329197
TI  - Gamma scintigraphy for testing bioequivalence: a case study on two cromolyn
      sodium nasal spray preparations.
AB  - The present work was carried out to study the deposition patterns and clearance
      of technetium-99m (99mTc) DTPA labeled cromolyn sodium (CS) solutions when
      administered from two different CS nasal products using gamma scintigraphy. Five
      healthy volunteers received a single dose with complete crossover design
      involving treatment A (test formulation) and treatment B (reference formulation).
      The deposition patterns as well as the changes in distribution of the
      radiolabeled CS solutions due to the mucociliary transport were monitored by
      gamma scintigraphy. Primary deposition of the aforementioned nasal solutions
      occurred in the anterior portion of the nose. After migration into the posterior
      nasal cavity, the solutions were rapidly cleared by ciliary action into the
      nasopharynx where it was swallowed. The test product of cromolyn sodium was shown
      to be equivalent to the reference product with regard to nasal deposition and
      clearance. The results from this study indicate that external gamma scintigraphy
      can be used to demonstrate the equivalence of nasal sprays that are intended for
      local therapeutic action where the drug is not systemically absorbed into the
      blood circulation. Furthermore, a non-invasive imaging method such as
      rhinoscintigraphy may prove to be a useful technique to be utilized during the
      regulatory approval process for local-acting nasal products, and may facilitate
      the early introduction of these products to the market.

PMID- 18329198
TI  - The effects of fatty acids in propylene glycol on the percutaneous absorption of
      alendronate across the excised hairless mouse skin.
AB  - The effects of fatty acids at various concentrations in propylene glycol (PG) on
      the in vitro permeation of alendronate from solution formulations and formulated
      pressure-sensitive adhesive (PSA) transdermal delivery systems through excised
      hairless mouse skin were investigated. Caprylic acid, capric acid, lauric acid,
      oleic acid and linoleic acid at concentrations of 3, 6 and 10% were employed as a
      fatty acid. The highest maximum permeation flux was obtained with 3% capric acid
      in PG followed by 6% capric acid and 3% oleic acid from solution formulations;
      the enhancement factor by the addition of 3% capric acid to PG was 20.5 compared
      to PG alone. On the contrary, from PSA transdermal delivery systems, the highest
      enhancement factor of 2.9 was attained with 6% caprylic acid in PG compared to PG
      alone. The maximum permeation flux and lag time from PSA transdermal delivery
      systems by the addition of 6% caprylic acid to PG were 195.68+/-26.6 ng/cm2/h and
      0.6+/-0.3h whereas PG without fatty acids showed 67.3+/-5.8 ng/cm2/h and 0.5+/
      0.4h, respectively. The PSA transdermal delivery systems initially provided very
      high permeation rate followed by a gradual decrease regardless of the fatty
      acids. The highest release rate was also obtained with the formulation containing
      6% caprylic acid in PG although release rates were not matched with permeation
      rates perfectly. In conclusion, for effective transdermal delivery system of
      alendronate, 6% caprylic acid in PG could be employed.

PMID- 18329199
TI  - Effect of fluidisation activity on end-point detection of a fluid bed drying
      process.
AB  - The influence of inlet air humidity variations on fluid bed drying end-point
      detection was the primary focus here. Various drying end-point criteria based on
      temperature and humidity measurements were compared. Seasonally changing inlet
      air humidity affects the moisture content of the finished granules, as long as
      the drying process remains unchanged. However, a specific moisture content of the
      finished granules is commonly desired after fluid bed drying. When experimental
      batches of varying inlet air humidity were compared at the beginning of the
      drying phase, the temperature of the granules increased linearly as the humidity
      of the inlet air increased. This effect causes variation in moisture contents of
      the final granules of different batches when the fixed temperature of the mass is
      used as an end-point criterion. With varying inlet air humidity, the often used
      DeltaT temperature difference method resulted in more precise estimation of the
      drying end-point than the constant temperature criterion. In this study new
      insights were found into the correlation between moisture content and temperature
      of the fluidising mass. Fluidisation activity greatly affected detection of
      drying end-point. Use of the DeltaT criterion requires proper fluidisation
      throughout the process.

PMID- 18329200
TI  - Release behavior of salicylic acid in supramolecular hydrogels formed by l
      phenylalanine derivatives as hydrogelator.
AB  - Supramolecular hydrogels were prepared from l-phenylalanine derivatives as novel
      hydrogelators. Salicylic acid (SA), acting as a model drug, was entrapped in the
      supramolecular hydrogels. The release behavior of SA molecules in the
      supramolecular hydrogels was investigated by using UV-vis spectroscopy. The
      influence of the concentration of the hydrogelator, pH values of the accepting
      media, the temperature, and the concentration of SA on the release behavior of SA
      was investigated under static conditions. The results indicated that the release
      rate of SA in the supramolecular hydrogels was slightly retarded with an increase
      of the hydrogelator concentration. Also, the release rates of SA increased with
      an increase of temperature and with the SA content. Furthermore, the release
      behavior of SA was found to be different at various pH values in buffers as
      accepting media. The study of the release kinetics indicated that the release
      behavior of SA was in accord with the Higuchi equation and the diffusion
      controlled mechanism involved in the Fickian model.

PMID- 18329201
TI  - Tumor-specific antibody-mediated targeted delivery of Doxil reduces the
      manifestation of auricular erythema side effect in mice.
AB  - A mucocutaneous reaction in mice associated with Doxil treatment was identified
      as auricular erythema (AE). Given that the immuno-targeting of Doxil to tumors
      was found to influence also its systemic biodistribution pattern, the attempt was
      made to exploit a specific targeting of Doxil to reduce the manifestation of this
      adverse reaction. This problem is of general significance, since cutaneous
      reactions often lead to alterations of Doxil dosing regimen in patients and might
      subsequently compromise the therapeutic outcome of cancer treatment. Tumor
      bearing mice were used to study the biodistribution and skin-tissue accumulation
      effects of the tumor-targeted Doxil (the clinically used anti-cancer formulation)
      coupled with the anti-cancer monoclonal 2C5 antibody (mAb 2C5) as well as AE
      caused by Doxil application. The modification of Doxil with mAb 2C5 resulted in a
      significant decrease in the normal skin accumulation of doxorubicin compared to
      original Doxil and substantially reduced AE. The frequency of AE was decreased by
      three to fourfold with the mAb 2C5-modified doxorubicin-loaded long-circulating
      liposomes. Thus, targeting of Doxil with the anti-cancer mAb 2C5 not only can
      increase the tumor-specific accumulation of the drug, but also diminishes the
      cutaneous side effect of the original Doxil therapy.

PMID- 18329202
TI  - Controlled delivery of aspirin: effect of aspirin on polymer degradation and in
      vitro release from PLGA based phase sensitive systems.
AB  - The objective of this study was to develop poly (d,l-lactide-co-glycolide) (PLGA)
      based injectable phase sensitive in situ gel forming delivery system for
      controlled delivery of aspirin, and to characterize the effect of drug/polymer
      interaction on the in vitro release of aspirin and polymer degradation. Aspirin
      was dissolved into PLGA solution in 1-methyl-2-pyrrolidone. Poly(ethylene
      glycol)400 was used as plasticizer to reduce initial burst release. The solution
      formulation was injected into aqueous release medium to form a gel depot.
      Released samples were withdrawn periodically and assayed for aspirin content by
      high performance liquid chromatography. The effect of aspirin on the degradation
      of PLGA matrix was evaluated using Proton Nuclear Magnetic Resonance and Gel
      Permeation Chromatography. PLGA based in situ gel forming formulations controlled
      the in vitro release of aspirin for 7 days only. Analysis of PLGA matrix
      residuals revealed that PLGA in aspirin loaded formulations exhibited a
      significantly (p<0.05) faster degradation compared to blank formulations. These
      findings suggest that aspirin causes an unusually faster degradation of PLGA.
      Such faster degradation of PLGA has not been noticed for any other drugs reported
      in the literature.

PMID- 18329203
TI  - Drug release responses of zinc ion crosslinked poly(methyl vinyl ether-co-maleic
      acid) matrix towards microwave.
AB  - The drug release characteristics of beads made of poly(methyl vinyl ether-co
      maleic acid) using Zn2+ as the crosslinking agent were investigated with respect
      to the influence of microwave irradiation. The beads were prepared by an
      extrusion method with sodium diclofenac as a model water-soluble drug. They were
      subjected to microwave irradiation at 80W for 5 and 20 min, and at 300W for 1 min
      20s and 5 min 20s. The profiles of drug dissolution, drug content, drug-polymer
      interaction and polymer-polymer interaction were determined by dissolution
      testing, drug content assay, differential scanning calorimetry and Fourier
      transform infrared spectroscopy. Treatment of beads by microwave at varying
      intensities of irradiation can aid to retard the drug release with a greater
      reduction extent through treating the beads for a longer duration of irradiation.
      The treatment of beads by microwave induced the formation of multiple polymeric
      domains of great strength and extent of polymer-polymer and drug-polymer
      interaction. The release of drug from beads was retarded via the interplay of O
      H, N-H, C-H, (CH2)n and C-O functional groups of these domains, and was mainly
      governed by the state of polymer relaxation of the matrix unlike that of the
      untreated beads of which the release of drug was effected via drug diffusion and
      polymer relaxation. In comparison to Ca2+ crosslinked matrix which exhibited
      inconsistent drug release retardation behavior under the influence of microwave,
      the extent and rate of drug released from the Zn2+ crosslinked beads were greatly
      reduced by microwave and the release of drug from these beads was consistently
      retarded in response to both high and low intensity microwaves.

PMID- 18329204
TI  - The effectiveness of N-acetyl-L-cysteine (L-NAC) in the prevention of severe
      noise-induced hearing loss.
AB  - Three groups of chinchillas were exposed to a nonGaussian continuous broadband
      noise at an Leq=10 5dB SPL, 8h/d for 5d. One group (N=6) received only the noise.
      A second group (N=6) received the noise and was additionally treated with L-NAC
      (325 mg/kg, i.p.). Treatment was administered twice daily for 2d prior to
      exposure and for 2d following the exposure. During exposure the animals received
      the L-NAC just prior to and immediately after each daily exposure. The third
      group (N=4) was exposed to the noise and received saline injections on the same
      schedule as the L-NAC treated animals. Auditory evoked potential recordings from
      the inferior colliculus were used to estimate pure tone thresholds and surface
      preparations of the organ of Corti quantified the sensory cell population. In all
      three groups PTS exceeded 50 dB at 2.0k Hz and above with severe sensory cell
      loss in the basal half of the cochlea. There was no statistically significant
      difference among the three groups in all measures of noise-induced trauma.
      Treatment with L-NAC did not reduce the trauma produced by a high-level, long
      duration, broadband noise exposure.

PMID- 18329205
TI  - Effects of essential oil from Croton tiglium L. on intestinal transit in mice.
AB  - AIM OF THE STUDY: Croton tiglium (Croton tiglium L., Euphorbiaceae) is widely
      used as a herb for treatment of gastrointestinal disturbances. Previous studies
      established its purgative and inflammational properties. The present study aimed
      to investigate the effects of Croton tiglium oil (CO) on intestinal transit in
      mice. MATERIALS AND METHODS: Gastrointestinal transit in mice and contractile
      characteristics of isolated intestinal strips from mice were evaluated.
      Intestinal inflammation was confirmed by histological examination. RESULTS: Low
      dose of CO increased the gastrointestinal transit of charcoal and barium meal as
      well as the production of fecal pellets in mice. In contrast, high dose exerted
      inhibitory effects. For normal colonic circular strips, both high and low dose of
      CO inhibited the contractile frequency. Low doses (0-20 microg/ml) of CO enhanced
      the phasic contractions, while high doses (>40 microg/ml) reduced them. Colonic
      longitudinal strips in CO-treated mice were less sensitive to electrical field
      stimulation than those in control mice. The contraction of colonic longitudinal,
      colonic and jejunal circular strips in CO-treated mice was more sensitive to
      atropine than that in control mice. CONCLUSIONS: CO might modulate
      gastrointestinal motility and induce intestinal inflammation related to
      immunological milieu and motor activity. Our findings may highlight the ethno
      medical uses of Croton tiglium on intestinal disorders.

PMID- 18329206
TI  - Plasma antidiuretic hormone in cases with the early onset of profound unilateral
      deafness.
AB  - OBJECTIVE: The p-ADH level in cases of juvenile unilateral profound deafness
      (JUPD) and the timecourse of the level were examined to investigate whether or
      not an increase of p-ADH is involved in the development of delayed endolymphatic
      hydrops (DEH) in JUPD. MATERIALS AND METHODS: In 90 consecutive patients with
      unilateral profound or total sensorineural deafness with the onset in early
      childhood, pure-tone audiometric examination and the measurement of p-ADH and
      plasma osmolality (p-OSM) were followed up once or twice a year as far as
      possible. At every testing, we performed careful history-taking about episodic
      vertigo/dizziness, fluctuant hearing loss, and tinnitus in order to find out
      whether patients had experienced these clinical signs of the development of DEH.
      RESULTS: Means and standard deviation (S.D.) of p-ADH level and osmolality in all
      samples tested (n=368) were 7.3+/-7.0 pg/mL (0.7-52.0 pg/mL), and 288.6+/-4.4
      mOsm/L (273-306 mOsm/L), respectively. The mean of p-ADH level was much higher
      than those previously reported in children and adolescents. High levels of p-ADH
      (over 5.0 pg/mL) were often observed in subjects between 6 and 19 years of age,
      but not so frequently in subjects of 20 years of age or older. Long-term follow
      up of p-ADH levels revealed that DEH frequently developed in cases with
      persistent elevation of p-ADH. CONCLUSIONS: The elevation of p-ADH is likely to
      promote the development of DEH in cases of JUPD, although the underlying
      mechanism remains to be elucidated.

PMID- 18329207
TI  - Malignant phosphaturic mesenchymal tumor, mixed connective tissue variant of the
      tongue.
AB  - The majority of the oncogenic osteomalacia-associated mesenchymal tumors are
      considered to belong to the category of phosphaturic mesenchymal tumors, mixed
      connective tissue (PMTMCT) variant, of which malignant cases are very rare. Here
      we report a case of a recurrent malignant PMTMCT variant which arose in the
      tongue. The patient was treated with surgery at an initial treatment and the
      first recurrence. In accordance with the tumor recurrence and resection, the
      hypophosphatemia progressed and improved. However, hypophosphatemia did not
      progress after receiving radiation therapy at the second recurrence even though
      the recurrent tumor gradually increased its size. These results suggest clinical
      feature of malignant PMTMCT could be changed by radiation therapy. Thus, this
      report could add an insight to the nature of PMTMCT.

PMID- 18329208
TI  - Risk of respiratory distress in the patients who were applied nasal packing at
      the end of nasal surgery.
AB  - OBJECTIVE: This prospective study investigated the risk of respiratory distress
      in the patients who were applied nasal packing at the end of nasal surgery; and
      effects of nasal packing on consciousness level while the patients were awake or
      asleep, measured by Bispectral Index (BIS). METHODS: The study group consisted of
      15 adult patients (10 male, 5 female), who were applied nasal packing at the end
      of nasal surgery. The control group consisted of 15 adult patients (10 male, 5
      female), who received general anesthesia for various reasons. In the study and
      control groups, BIS index, respiratory rate, peripheral oxygen saturation, pulse
      per minute and blood pressure were measured at seven different times. RESULTS:
      There was no statistically significant difference between BIS indexes of the
      study and control groups. In the fourth hour after sleep (AS-4h), respiratory
      rate of the study group was significantly lower than that of the control group.
      In the fourth hour after the anesthesia (AA-4h), oxygen saturation value of the
      study group was lower than that of the control group. CONCLUSION: We conclude
      that in patients who are applied nasal packing at the end of nasal surgery; at AA
      4h and AS-4h times, there may be risk of decrease in the oxygen saturation and
      respiratory rate parameters, respectively. Therefore, it is necessary to monitor
      non-invasive respiratory parameters and to give enriched oxygen by an oral
      catheter.

PMID- 18329209
TI  - Hyperoxic exposure leads to cell death in the developing brain.
AB  - Premature infants have high incidence of motor and cognitive impairment in later
      life. Supraphysiological oxygen concentrations are routinely used in neonatal
      intensive care units and elicit injury to premature lungs and retina. Since the
      effects of hyperoxia on the developing brain are scarce, we studied the effects
      of high oxygen on this tissue. Wistar rat pups were exposed from birth until day
      5 to 21% or 80% oxygen. The neuronal density and apoptosis in CA1 and dentate
      gyrus of hippocampus, prefrontal cortex, parietal cortex, subiculum, and
      retrosplenial cortex were assessed by immunohistochemistry and ELISA cell death
      assay. Neuronal density of the investigated brain areas were significantly
      decreased in the hyperoxia group. Furthermore, using ELISA cell death and TUNEL
      assays, we observed increased cell death in the developing brain. Our results
      show that hyperoxia induces cell death in the developing rat brain. This may be
      one of the important mechanisms that cause motor and cognitive impairment in
      later life of premature infants.

PMID- 18329210
TI  - [Epidemiology and environment: new relationship?].

PMID- 18329211
TI  - [Is the apocalypse for tomorrow?].

PMID- 18329212
TI  - TMJ disorders and pain: assessment by contrast-enhanced MRI.
AB  - Though magnetic resonance (MRI) is a widely accepted standard for the assessment
      of patients with temporomandibular joint (TMJ) disorders, efforts to correlate
      symptoms to MRI findings have often given controversial results. Aim of this
      study was to investigate the correlation between TMJ pain and findings of
      contrast-enhanced MRI. Thirty-eight consecutive patients with TMJ dysfunction
      syndrome (study group) were examined with MRI. Protocol included T2 turbo spin
      echo sequence, T1 spin-echo sequence, and T2 gradient-echo (acquired with closed
      jaw, at intermediate and maximal opening). Post-contrast phase was obtained
      through a fat sat 3D T1 gradient-echo sequence (VIBE). Post-contrast findings in
      the study group were matched with those obtained in a control group of 33
      patients submitted to MRI of the paranasal sinuses. Statistically significant
      difference was found between condylar medullary bone enhancement in painful TMJ,
      in painless TMJ and control group. In addition the average thickness of joint
      soft tissue enhancement in painful TMJ was superior to painless TMJ (p<0.0001)
      and to control group. On multivariate logistic regression analysis, the odds
      ratio that a painful TMJ showed disk displacement, osteoarthrosis, effusion and
      JST enhancement were 3.05, 3.18, 1.2 and 11.36, respectively. Though not
      histologically proven, TMJ enhancement could reflect the presence of inflammation
      in painful joints. Furthermore, the administration of contrast could be of help
      for the assessment of patients with orofacial pain, particularly when clinical
      exploration is insufficient to ascribe the pain to TMJ.

PMID- 18329213
TI  - Tumor tissue characterization evaluating the luciferase activity under the
      control of a hsp70 promoter and MR imaging in three tumor cell lines.
AB  - We investigated the luciferase activity under the control of a hsp70 promoter and
      MR imaging for three tumor cell lines. Three tumor cell lines, SCCVII, NIH3T3 and
      M21 were transfected with a plasmid containing the hsp70 promoter fragment and
      the luciferase reporter gene and grown in mice. Bioluminescence imaging of the
      tumors was performed every other day. MR imaging, pre- and post-contrast T1-wt
      SE, T2-wt FSE, Diffusion-wt STEAM-sequence, T2-time determination were obtained
      on a 1.5-T GE MRI scanner at a tumor size of 600-800 mm(3) and 1400-1600 mm(3).
      Comparing the different tumor sizes the luciferase activity of the M21 tumors
      increased about 149.3%, for the NIH3T3 tumors about 47.4% and for the SCCVII
      tumors about 155.8%. Luciferase activity of the M21 tumors (r=0.82, p<0.01) and
      the SCCVII tumors (r=0.62, p=0.03) correlated significant with the diffusion
      coefficient. In the NIH3T3 tumors the best correlation between the luciferase
      activity and the MRI parameter was seen for the SNR (T2) values (r=0.78, p<0.01).
      The luciferase activity per mm(3) tumor tissue correlated moderate with the
      contrast medium uptake (r=0.55, p=0.01) in the M21 tumors. In the NIH3T3 and
      SCCVII tumors a negative correlation (r=-0.78, p<0.01, respectively, r=-0.49,
      p=0.02) was found with the T2 time. Different tissue types have different
      luciferase activity under the control of the same hsp70 promoter. The combination
      of MR imaging with bioluminescence imaging improves the characterization of tumor
      tissue giving better information of this tissue on the molecular level.

PMID- 18329214
TI  - Multidetector computed tomography arthrography of the knee: diagnostic accuracy
      and indications.
AB  - PURPOSE: To evaluate the diagnostic accuracy and indications of arthrography with
      multidetector computed tomography (arthro-MDCT) of the knee, in patients with
      absolute or relative contraindications to MRI and in patients with periarticular
      metal implants using diagnostic arthroscopy as the gold standard. MATERIALS AND
      METHODS: After intra-articular injection of iodixanol and volumetric acquisition,
      68 knees in patients of both sexes (30 females, 38 males, age range 32-60 years)
      were examined with a 16-detector-row CT scanner. The patients had arthralgia but
      no radiologically detected fractures. They could not be studied by MRI either
      because of absolute contraindications (subcutaneous electronic implants),
      surgical metal implants or claustrophobia. In 37 of 68 patients who had had
      previous knee surgery, the arthro-CT examination was preceded by an MRI on the
      same day. All examinations were interpreted by two experienced musculoskeletal
      radiologists. The findings were compared with arthroscopic findings carried out
      within 28 days of the CT study. RESULTS: In non-operated patients the comparison
      between arthro-MDCT and arthroscopy showed sensitivity and specificity ranging
      between 86% and 100%. In the 37 operated knees, arthro-MDCT had an accuracy of
      95% compared with 53% of the MRI. Inter-observer agreement was almost perfect
      (K=0.97) in the evaluation of all types lesions, both on MDCT and MRI. When
      arthro-MDCT was compared with MRI in post-operative patients by a McNemar test, a
      significant difference (p<0.05) was found between these two techniques.
      CONCLUSIONS: Arthro-MDCT of the knee is a safe technique that provides accurate
      diagnosis in identifying chondral, fibrocartilaginous and intra-articular
      ligamentous lesions, in patients that cannot be evaluated by MRI, and in patients
      after surgical.

PMID- 18329215
TI  - Analysis of flurbiprofen, ketoprofen and etodolac enantiomers by pre-column
      derivatization RP-HPLC and application to drug-protein binding in human plasma.
AB  - A stereoselective reversed-phase high-performance liquid chromatography (HPLC)
      assay to determine the enantiomers of flurbiprofen, ketoprofen and etodolac in
      human plasma was developed. Chiral drug enantiomers were extracted from human
      plasma with liquid-liquid extraction. Then flurbiprofen and ketoprofen
      enantiomers reacted with the acylation reagent thionyl chloride and pre-column
      chiral derivatization reagent (S)-(-)-alpha-(1-naphthyl)ethylamine (S-NEA), and
      etodolac enantiomers reacted with S-NEA using 1-(3-dimethylaminopropyl)-3-ethyl
      carbodiimide (EDC) and 1-hydroxybenzotriazole (HOBT) as coupling agents. The
      derivatized products were separated on an Agilent Zorbax C18 (4.6 mm x 250 mm, 5
      microm) column with a mixture of acetonitrile-0.01 mol.L(-1) phosphate buffer (pH
      4.5) (70:30, v/v) for flurbiprofen enantiomers, acetonitrile-0.01 mol.L(-1)
      phosphate buffer (pH 4.5) (60:40, v/v) for ketoprofen enantiomers and methonal
      0.01 mol.L(-1) potassium dihydrogen phosphate buffer (pH 4.5) (88:12, v/v) for
      etodolac enantiomers as mobile phase. The flow of mobile phase was set at 0.8
      mL.min(-1) and the detection wavelength of UV detector was set at 250 nm for
      flurbiprofen and ketoprofen enantiomers and 278 nm for etodolac enantiomers. The
      assay was linear from 0.5 to 50 microg.mL(-1) for each enantiomer. The inter- and
      intra-day precision (R.S.D.) was less than 10% and the average extraction
      recovery was more than 87% for each enantiomer. The limit of quantification for
      the method was 0.5 microg.mL(-1) (R.S.D.<10%, n=5). The method developed was used
      to study the drug-protein binding of flurbiprofen, ketoprofen and etodolac
      enantiomers in human plasma. The results showed that the stereoselective binding
      of etodolac enantiomer was observed and flurbiprofen and ketoprofen enantiomers
      were not.

PMID- 18329216
TI  - Spectrophotometric monitoring of nimesulide photodegradation by a combined hard
      soft multivariate curve resolution-alternative least square method.
AB  - Nimesulide, a Cox-2 inhibitor anti-inflammatory drug, is a light sensitive
      compound and its biological activity is decreased upon photodegradation. The
      photodegradation kinetic of nimesulide was investigated spectrophotometrically
      using multivariate curve resolution analysis to overcome spectral overlapping of
      reactant and degradation products. The absorbance spectra of the nimesulide
      methanolic solution, exposed to daily sunlight, were recorded at different times.
      Three absorbing chemical species, coexisted in the reaction system, were detected
      by application of factor analysis to the absorbance data matrix. The soft
      modeling multivariate curve resolution-alternative least square (MCR-ALS)
      analysis of the evolutionary absorbance data revealed that nimesulide undergoes
      photodegradation through a two-step consecutive manner, where both steps obey
      first-order kinetic. By application of the kinetic hard model constraint to the
      MCR-ALS analysis, an excellent agreement was obtained between the fitted
      concentration profiles and those obtained by soft method. The first-order rate
      constants of the first and second degradation products were calculated as 0.052
      (+/-0.007) and 0.009 (+/-0.001)h(-1), respectively. Finally, the pure spectra of
      the resolved chemical species were calculated, where that of nimesulide was the
      same as that obtained experimentally.

PMID- 18329217
TI  - Comparison of usefulness of plasma procalcitonin and C-reactive protein
      measurements for estimation of severity in adults with community-acquired
      pneumonia.
AB  - Although procalcitonin (PCT) measurement has been performed in patients with
      infectious diseases, there are few reports on its usefulness in community
      acquired pneumonia (CAP) associated with systemic inflammatory response syndrome
      (SIRS). We investigated 88 patients who visited the internal medicine departments
      of Nagasaki University Hospital, Nagasaki, Japan, and its 11 affiliated hospitals
      in Japan because of CAP with or without SIRS. Of the 88 patients, 15 (17.0%), 43
      (48.9%), and 30 (34.1%) were judged to have severe, moderate, and mild CAP,
      respectively. Although 87 patients (98.9%) had C-reactive protein (CRP) levels
      exceeding 0.3 mg/dL, only 30 patients (34.1%) had PCT levels more than 0.5 ng/mL.
      In addition, 93.3% (28/30) of patients with mild CAP had negative PCT, and 48.3%
      (28/58) of patients positive for PCT had moderate or severe CAP. Our findings
      suggest that PCT level might be more useful for estimating CAP severity than CRP
      level at the 1st visit.

PMID- 18329218
TI  - In vitro activity of daptomycin against methicillin- and multi-resistant
      Staphylococcus haemolyticus invasive isolates carrying different mec complexes.
AB  - Fifty methicillin and multi-resistant Staphylococcus haemolyticus (MRSH) strains,
      were tested against daptomycin and comparators. Daptomycin showed an overall
      MIC(90) value of 1 mg/L, similar to that of quinopristin/dalfopristin and lower
      than the values for vancomycin (2 mg/L), linezolid (2 mg/L) and teicoplanin (32
      mg/L). Eighteen strains showed heteroresistant subpopulations with teicoplanin,
      whereas two strains were also heteroresistant to vancomycin and these sub
      populations retained susceptibility to daptomycin. Our results show the good in
      vitro activity of daptomycin in MRSH strains possessing a multi-resistant
      phenotype. Clinical data on daptomycin efficacy are necessary to confirm our in
      vitro findings.

PMID- 18329219
TI  - Evidence that 3-hydroxyisobutyric acid inhibits key enzymes of energy metabolism
      in cerebral cortex of young rats.
AB  - 3-Hydroxyisobutyric aciduria is an inherited metabolic disease caused by 3
      hydroxyisobutyryl-CoA dehydrogenase deficiency. Tissue accumulation and high
      urinary excretion of 3-hydroxyisobutyric acid is the biochemical hallmark of this
      disorder. Clinical phenotype is heterogeneous and generally includes dysmorphic
      features, delayed motor development, profound mental impairment, and acute
      encephalopathy. Lactic acidemia is also found in the affected patients,
      indicating that mitochondrial dysfunction may be involved in the pathophysiology
      of this disorder. Therefore, the aim of the present work was to investigate the
      in vitro effect of 3-hydroxyisobutyric acid (0.1, 0.5 and 1mM) on essential
      enzymes of energy metabolism, namely the activities of the respiratory chain
      complexes I-V, total, cytosolic and mitochondrial creatine kinase and Na(+), K(+)
      ATPase in cerebral cortex homogenates of 30-day-old rats. We also measured the
      rate of oxygen consumption in brain mitochondrial preparations in the presence of
      3-hydroxyisobutyric acid. 3-Hydroxyisobutyric acid significantly reduced complex
      I-III (20%), without affecting the other activities of the electron transport
      chain. Furthermore, 3-hydroxyisobutyric acid did not change state III, state IV
      and the respiratory control ratio in the presence of glutamate/malate or
      succinate, suggesting that its effect on cellular respiration was weak. On the
      other hand, the activities of total and mitochondrial creatine kinase, but not
      cytosolic creatine kinase, were inhibited (30%) by 3-hydroxyisobutyric acid. We
      also observed that 3-hydroxyisobutyric acid-induced inhibition of mitochondrial
      creatine kinase activity was fully prevented by pre-incubation of the homogenates
      with reduced glutathione, alpha-tocopherol or the combination of superoxide
      dismutase plus catalase, suggesting that this inhibition was mediated by
      oxidation of essential thiol groups of the enzyme probably by superoxide,
      hydrogen peroxide and/or peroxyl radicals. It was also demonstrated that Na(+),
      K(+)-ATPase activity from synaptic plasma membranes was markedly suppressed (37%)
      by 3-hydroxyisobutyric acid and that this effect was prevented by alpha
      tocopherol co-incubation implying that peroxyl radicals were probably involved in
      this action. Considering the importance of the affected enzyme activities for
      brain metabolism homeostasis and neurotransmision, it is suggested that increased
      tissue levels of 3-hydroxyisobutyric acid may contribute to the neurodegeneration
      of patients affected by 3-hydroxyisobutyric aciduria and possibly explain
      previous reports describing elevated production and excretion of lactate.

PMID- 18329220
TI  - Unmet supportive care needs and interest in services among patients with a brain
      tumour and their carers.
AB  - OBJECTIVES: To assess the supportive care needs and interest in related services
      among brain tumour patients and their carers and to compare the level of unmet
      needs to other cancer populations. METHODS: A cross-sectional survey was posted
      to 363 households who were subscribed to the Queensland Cancer Fund Brain Tumour
      Support Service in 2005. Overall, 75 patients and 70 carers (response rate 29.8%)
      returned completed questionnaires. Measures were the Supportive Care Needs Survey
      (SCNS-34) and a brain tumour specific subscale for patients and carers, as well
      as the Hospital Anxiety and Depression Scale (HADS). RESULTS: Patients most
      frequently reported requiring support to overcome fatigue, uncertainty about the
      future and not being able to do the things they used to do. Carers wanted help
      dealing with fears about the patients mental or physical deterioration, with the
      impact caring had on their own life, and with reducing stress in the patient's
      life. Among patients, 30% reported anxious mood and 17% depressed mood on the
      HADS, while corresponding numbers for carers were 40% and 10%, respectively.
      Patients and/or carers with higher than average supportive care needs expressed
      greater interest in support services, such as those to improve physical activity,
      using community services more effectively and to manage stress. Greater emotional
      distress predicted higher supportive care needs (e.g. odds ratio depressed
      patients=2.11; (95% confidence interval 1.10-4.03), while no association was
      detected between patients' or carers' demographic characteristics, or patients'
      self-reported medical status and higher than average supportive care needs.
      CONCLUSION: The level of unmet supportive care needs observed among patients with
      a brain tumour and their carers is similar to that observed among cancer
      populations with metastatic disease. PRACTICE IMPLICATIONS: Interventions for
      this group should integrate lifestyle, coping support, and neuropsychological
      rehabilitation.

PMID- 18329221
TI  - Symptoms and sleep patterns during inpatient treatment of methamphetamine
      withdrawal: a comparison of mirtazapine and modafinil with treatment as usual.
AB  - The safety and tolerability of modafinil (400 mg/day, n = 14) and mirtazapine (60
      mg/day, n = 13) in inpatient methamphetamine withdrawal treatment were compared
      to a historical comparison group receiving treatment as usual (pericyazine, 2.5
      10 mg/day, n = 22). Modafinil and mirtazapine were well tolerated, producing
      minimal positive subjective effects and no discontinuation effects in this open
      label study. Side effects were mild and transient. Aches and pains were most
      commonly reported by participants receiving mirtazapine, whereas headache was
      reported by modafinil-treated participants. Modafinil-treated participants had a
      milder withdrawal syndrome as measured by the Amphetamine Cessation Symptom
      Assessment and less sleep disturbance in comparison to mirtazapine. Pericyazine
      was associated with a more severe withdrawal syndrome in comparison to
      mirtazapine and modafinil. Both modafinil and mirtazapine were safe and well
      tolerated in methamphetamine withdrawal treatment. However, these early findings
      of efficacy in symptom amelioration should be replicated in an adequately
      powered, randomized, placebo-controlled double-blind design.

PMID- 18329223
TI  - Services received and treatment outcomes in day-hospital and residential
      programs.
AB  - This longitudinal health services study (N = 733) (1) examines the impact of
      services received on 6-month outcomes, and (2) compares day-hospital to
      residential programs on services received. Services were measured at 2, 4, and 8
      weeks postbaseline using a version of the Treatment Services Review. Higher odds
      of total sobriety at 6 months were associated with greater participation in (a)
      extracurricular (but not curricular) 12-step meetings, (b) sober recreational
      events, and (c) educational sessions. Program effects also emerged. Unexpectedly,
      extracurricular 12-step meeting attendance and the odds of having a sponsor were
      lower among residential (vs. day hospital) participants through 4 weeks, despite
      higher participation in curricular 12-step meetings among residential
      participants at 2 weeks. Still, residential participants reported higher
      involvement in sober recreation and informal peer socialization across most
      analyses. Findings suggest that residential and day-hospital programs might
      maximize outcomes by facilitating optional 12-step involvement and sober
      recreation, respectively.

PMID- 18329222
TI  - Substance abuse treatment in human immunodeficiency virus: the role of patient
      provider discussions.
AB  - Substance abuse treatment is associated with decreases in human immunodeficiency
      virus (HIV) risk behavior and can improve HIV outcomes. The purpose of this study
      was to examine factors associated with substance abuse treatment utilization,
      including patient-provider discussions of substance use issues. We surveyed 951
      HIV-infected adults receiving care at 14 HIV Research Network primary care sites
      regarding drug and alcohol use, substance abuse treatment, and provider
      discussions of substance use issues. Although 71% reported substance use, only
      24% reported receiving substance abuse treatment and less than half reported
      discussing substance use issues with their HIV providers. In adjusted logistic
      regression models, receipt of substance abuse treatment was associated with
      patient-provider discussions. Patient-provider discussions of substance use
      issues were associated with current drug use, hazardous or binge drinking, and
      Black race or ethnicity, though substance use was comparable between Blacks and
      Whites. These data suggest potential opportunities for improving engagement in
      substance abuse treatment services.

PMID- 18329224
TI  - Risk factors for a first-time drink-driving conviction among young men: a birth
      cohort study of all men born in Denmark in 1966.
AB  - Using a complete birth cohort of all young men born in 1966 in Denmark (N =
      43,403), the prevalence of a first-time drink-driving conviction among young men
      is estimated. More than 7% of the total male birth cohort was so convicted before
      the age of 27 years. In an examination of risk factors for a first-time drink
      driving conviction, young adults coming from potentially vulnerable groups have
      an increased risk. Earlier criminal convictions of various types were also
      significant predictors of drink driving. Situational pressures also play a part
      and are controlled for, with the risk of a drink-driving conviction increased
      substantially in rural areas compared to metropolitan areas. The study concludes
      that disadvantages during adolescence, including parental substance abuse, having
      a teenage mother, and domestic violence, are associated with a first-time drink
      driving conviction.

PMID- 18329225
TI  - Methamphetamine dependence and human immunodeficiency virus risk behavior.
AB  - We examined human immunodeficiency virus (HIV)-related risk behaviors among
      methamphetamine (MA)-dependent users. Secondary data analysis was performed on
      data from a large clinical trial: The Methamphetamine Treatment Project (N =
      784). All MA-dependent participants were enrolled in an outpatient treatment
      program, receiving either a standardized psychosocial protocol (Matrix model) or
      treatment-as-usual. HIV-related risk behavior, including injection and unsafe
      sexual practices, was assessed using the AIDS Risk Assessment at baseline,
      treatment discharge, and 6, 12, and 36 months following treatment participation.
      Results indicated that HIV risk behaviors substantially decreased over time.
      Treatment factors (retention and completion) and frequency of MA use were both
      positively associated with increased reduction of HIV risk behaviors. The
      findings suggested that treatment of MA dependence is promising for reducing
      behaviors that have been shown to transmit HIV.

PMID- 18329226
TI  - Outcomes using two tailored behavioral treatments for substance abuse in urban
      gay and bisexual men.
AB  - This project evaluated two behavioral therapies for substance abuse and
      concomitant sexual risk behaviors applied to primarily stimulant-abusing gay and
      bisexual men in Los Angeles. One hundred twenty-eight participants were randomly
      assigned to 16 weeks of a gay-specific cognitive-behavioral therapy (GCBT, n =
      64) or to a gay-specific social support therapy (GSST; n = 64), with follow-up
      evaluations at 17, 26, and 52 weeks after randomization. No overall statistically
      significant differences were observed between conditions along retention,
      substance use, or HIV-related sexual risk behaviors. All participants showed a
      minimum of twofold reductions in substance use and concomitant sexual risk
      behaviors from baseline to 52-week evaluations. Among methamphetamine-using
      participants, the GCBT condition showed significant effects over GSST for
      reducing and sustaining reductions of methamphetamine. Findings replicate prior
      work and indicate that GCBT produces reliable, significant, and sustained
      reductions in stimulant use and sexual risk behaviors, particularly in
      methamphetamine-abusing gay and bisexual men.

PMID- 18329227
TI  - Improving acceptance of naltrexone in community addiction treatment centers: a
      pilot study.
AB  - Alcoholism pharmacotherapies are underused in community addiction treatment
      settings, in part because individuals who practice in these settings--nonmedical
      addiction counselors and administrators--lack knowledge about and confidence in
      the value of adjunctive alcohol pharmacotherapies. We developed and tested an
      intervention to improve knowledge and attitudes about naltrexone. A team of
      researchers, physicians, addiction treatment counselors, and administrators
      collaborated to develop a naltrexone educational intervention designed for
      nonmedical addiction professionals. The intervention was compared with a control
      condition in a pilot study with 6 addiction treatment agencies (3 agencies per
      group). Participants (counselors and administrators, N = 84) were assessed before
      and 6 months after the intervention. Results revealed that the intervention
      significantly improved naltrexone knowledge, and participants who received the
      intervention reported greater satisfaction with the education they received, as
      well as greater use of the information. The effect of the intervention on
      attitudes about naltrexone was encouraging but did not to reach statistical
      significance. This study is the first reported attempt to develop and test an
      intervention specifically to improve acceptance of adjunctive medications for
      alcoholism among nonmedical addiction professionals.

PMID- 18329228
TI  - Undifferentiated mesenchymal stem cells seeded on a vascular prosthesis
      contribute to the restoration of a physiologic vascular wall.
AB  - BACKGROUND: We evaluated the possibility of restoring a physiologic vascular wall
      using undifferentiated mesenchymal stem cells (MSCs) seeded on a polyurethane
      vascular prosthesis. METHODS: Undifferentiated MSCs were seeded on a vascular
      prosthesis and implanted into Wistar male rats (weight, 350 g) to investigate
      differentiation into smooth muscle cells and to determine graft
      endothelialization in vivo. RESULTS: Seeded or nonseeded grafts were surgically
      implanted. Undifferentiated MSCs were first labelled for green fluorescent
      protein. After 2 weeks in vivo, MSC that were initially self-expanded on the
      graft in a monolayer were organized in a multicellular layer mimicking media of
      aortic adjacent wall. They coexpressed green fluorescent protein and smooth
      muscle proteins that were not present before the in vivo engraftment, indicating
      that in vivo conditions induced smooth muscle protein maturation.
      Undifferentiated MSC showed an electrophysiologic profile quite different than
      mature smooth muscle cells. In both in vitro- and in vivo-differentiated MSCs,
      adenosine triphosphate, an IP(3)-dependent agonist, induced an increase in
      calcium similar to that which occurred in mature smooth muscle cells. However,
      MSCs failed to respond to caffeine, a ryanodine receptor activator, indicating
      the absence of mature calcium signaling, and finally, contraction was absent.
      Endothelialization attested by immunohistology and scanning electron microscopy
      was greater in MSC-seeded grafts that prevent thrombosis. CONCLUSION: Only
      partial smooth muscle cell differentiation of MSCs resulted when seeded on
      vascular grafts, but MSCs spontaneously restore a media-like thick wall.
      Mesenchymal stem cells have a positive impact on in vivo endothelialization in
      rats that supports their potential for use in vascular surgery. CLINICAL
      RELEVANCE: Thrombosis of vascular prostheses is a major complication of surgery.
      We showed on rat aorta that mesenchymal stem cells seeded on polyurethane patch
      restore endothelium. It also induced incomplete smooth muscle differentiation. In
      the future, stem cell could prevent thrombosis of vascular prostheses.

PMID- 18329229
TI  - Liver resection for metastatic gastric cancer.
AB  - AIMS: Liver resection represents a curative treatment approach in patients
      suffering from liver metastases from gastric cancer. However, its value in the
      treatment of these patients remains controversial. This study was conducted to
      evaluate the safety and effectiveness of liver resection in these conditions and
      to identify criteria for the selection of suitable patients. METHODS: From
      January 1988 to December 2002, 24 patients underwent liver resection for
      metastatic gastric cancer. The outcome of these 24 patients was retrospectively
      reviewed using a prospective database. Patient, tumour and operative parameters
      were analyzed for their influence on long-term survival. RESULTS: One patient
      died and four patients (17%) developed complications during the postoperative
      course. The overall one-, three- and five-year survival was 38%, 16% and 10%,
      respectively. After curative resection (n=17), the one-, three- and five-year
      survival rate was 53%, 22% and 15%, respectively, and patients with metachronous
      metastases restricted to the liver (n=5) had a one-, three- and five-year
      survival of 80%, 40% and 40%, respectively. In the univariate analysis,
      extrahepatic manifestation showed in tendency (p=0.069) and resection margins
      statistically significant (p=0.005) influence on survival. The multivariate
      analysis revealed only resection margins as an independent prognostic factor for
      survival. CONCLUSIONS: Long-term survival can be achieved by liver resection in
      well selected patients and may be considered in the multidisciplinary treatment
      approach of metastatic gastric cancer. Patients with metastatic disease
      restricted to the liver in whom a curative resection can be achieved seem to be
      most suitable for liver resection.

PMID- 18329230
TI  - [Betablockers in perioperative period: drop the bombshell].

PMID- 18329231
TI  - Drug targeting of airway surface liquid: a pharmacological MRI approach.
AB  - Pharmacological MRI at 4.7 T was used to investigate the secretory response to
      Sylvestris pine oil stimuli in the rat airways, with the aim of developing an in
      vivo model in a small laboratory animal. The availability of such a model would
      greatly facilitate the drug discovery process using compounds active on airway
      surface liquid (ASL) production, and would make it possible to obtain information
      on chemoreceptoral mechanisms and to test the effects of environmental substances
      on the airways. T1- and T2-weighted images were acquired in the trachea and
      larynx before and at various times after exposure to pine oil. Several post
      processing procedures were tested in order to improve the visibility of the
      secretory response and to measure the enhancement of the signal intensity of ASL.
      A semiautomatic application software was written to localize and to measure the
      volume involved in the secretory response to a compound administration. A
      significant effect of the pine oil administration on the secretory response was
      founded in trachea (p<0.01) and in the salivary glands (p<0.01). 3D
      reconstructions of MRI data and virtual endoscopy permitted a quick visualization
      of tracheal morphology and localization of the greatest response to stimulus. The
      study demonstrated that, despite technical problems due to the air/tissue
      interface and to the small dimensions of the experimental animals, the secretory
      response can be evaluated and the pharmacological MRI (phMRI) of the rat airways
      is feasible. The potential and the limitations of phMRI investigation in drug
      targeting of ASL are discussed.

PMID- 18329232
TI  - [Quality and outcome assessment in gastrointestinal endoscopy: study of 202
      colonoscopies].
AB  - AIM: The aim of this study was to evaluate the quality of the medical care
      associated with the colonoscopies performed in our gastrointestinal endoscopy
      unit. This 6-month prospective, comparative study used process and result
      indicators. Its long-term objective was to improve the quality of care and to
      select a few pertinent quality indicators for continual monitoring. METHODS: An
      audit was conducted of all total colonoscopies performed at our general hospital
      from November 2005 through May 2006. It assessed the principal published process
      and result indicators for the medical aspects of the procedure as well as patient
      satisfaction (indication, procedure itself, results, complications,
      satisfaction). These indicators were also compared between endoscopists. RESULTS:
      During the 6-month study period, 202 total colonoscopies were performed. Waiting
      time for the procedure, appropriateness of the indication, proportion of
      colonoscopies completed, proportion of neoplastic lesions found, adequacy of
      bowel preparation, frequency of complications, and patient satisfaction were
      similar to and even above the standard values. However, patient information and
      the completeness of the legal documents were insufficient. Although the mean
      values were satisfactory, detailed individual analysis showed statistically
      significant differences between endoscopists. For example, the proportion of
      withdrawal times exceeding 6 minutes was 16.3%, 25.0% and 86.4% according to
      endoscopist. The mean number of polyps each removed per procedure was
      respectively 1, 2, and 3 (p<0.05). An improvement plan was implemented in view of
      these results, and appropriate simple indicators were selected for prospective
      monitoring. CONCLUSION: Despite the overall results, which essentially complied
      with standard guidelines, our prospective and comparative audit of colonoscopies
      pointed out significant variations between individual endoscopists and helped us
      to define improvement actions and indicators.

PMID- 18329233
TI  - [Temporary henna tattoos: Sometimes serious side effects].
AB  - Temporary henna tattoos are becoming increasingly popular among Western tourists
      during summer holidays, especially children, teenagers and young adults. Natural
      henna takes several hours to be absorbed into the skin, imparts a brownish-orange
      color, and causes very few allergic reactions. Para-phenylenediamine (PPD), a
      powerful allergen, is added to henna tattoo mixtures (black henna tattoo) to
      decrease application time and intensify the color. It is responsible for most of
      the complications reported after henna tattoos: localized or generalized contact
      dermatitis, hypertrophic or keloid scars, and temporary or permanent hyper- or
      hypopigmentation. More rarely, type I hypersensitivity reactions (urticaria,
      angioedema, or anaphylaxis) with potentially lethal outcomes have been reported.
      PPD allergy can induce cross-reactivity with other substances, such as hair dyes
      and textile azo dyes. Patch testing for PPD must be performed at a very diluted
      concentration (0.01% in vaseline) to avoid unnecessarily strong reactions and
      sensitization to PPD. In the absence of any legal control of henna tattooing
      practices, prevention requires the annual provision of information to Western
      consumers, especially young people and their parents.

PMID- 18329234
TI  - [Comparison of antimicrobial susceptibility of 1,217 Escherichia coli isolates
      from women with hospital and community-acquired urinary tract infections].
AB  - INTRODUCTION: The treatment of urinary tract infection (UTI) in women is based
      mainly on empirical antibiotic therapy. It requires up-to-date knowledge of the
      susceptibility patterns of the bacteria most commonly identified in that setting.
      The aim of this prospective study was to measure the antibiotic susceptibility of
      Escherichia coli isolates responsible for UTIs in women from a single area and to
      compare it in hospital and community settings. MATERIALS AND METHODS: From May
      2003 through April 2004, UTI was diagnosed in 1838 women around Rennes (France),
      893 of them inpatients admitted to the teaching hospital and 945 outpatients in
      the community. We determined the susceptibility to 7 antibiotics of the resulting
      1217 E. coli isolates. RESULTS: E. coli resistance rates in hospitalized and
      community patients were respectively 47.9% and 39.2% for aminopenicillins, 47.3%
      and 25.4% for coamoxiclav, 19.2% and 14.1% for cotrimoxazole, 14.3% and 5.7% for
      first-generation quinolones, and 8.9% and 3.7% for fluoroquinolones. All these
      rates were significantly higher among hospitalized patients (p<0.05). Conversely,
      resistance to injectable third-generation cephalosporins and fosfomycin was
      similar and infrequent in both groups. CONCLUSION: Comparisons with previous data
      show that activity of third-generation cephalosporins and fosfomycin on E. coli
      appears unchanged, in contrast to the increased resistance rates to other
      antibiotics usually prescribed for UTI.

PMID- 18329235
TI  - [Role of imaging in coronary disease].

PMID- 18329236
TI  - [Computed tomography of cerebromeningeal bleeding after head trauma].

PMID- 18329237
TI  - [Voluminous mediastinal neurofibroma in a child].
AB  - INTRODUCTION: Neurogenic tumors account for 30% of mediastinal tumors in
      children. The thoracic region is the most common site for neurofibromas. We
      report a case of a voluminous neurofibroma in a small girl. CASE: After 8 months
      of paraplegia, a 4-year-old girl underwent thoracic radiography and computed
      tomography as well as magnetic resonance imaging of the spine. These revealed a
      huge mediastinal mass continuing into the vertebral canal and compressing the
      cord. Histological examination after surgery confirmed the diagnosis of
      neurofibroma. At the follow-up examination a month later, the paraplegia had
      resolved. DISCUSSION: Neurofibromas may manifest as solitary tumors or may be one
      manifestation of neurofibromatosis. In mediastinal neurofibroma, thoracic
      radiography, and computed tomography can show the tumor, posterior vertebral
      scalloping, and enlarged neural foramina. MR imaging provides the exact anatomic
      location, as well as any compression and displacement caused by the tumor. This
      information is essential for deciding the exact extent of resection. MRI may also
      be helpful in postoperative management.

PMID- 18329238
TI  - [Value of intraoperative frozen-section analysis in thyroid surgery].
AB  - AIM OF STUDY: To assess the value of intraoperative frozen-section diagnosis in
      thyroid surgery and determine its limitations. METHODS: This retrospective study
      examined the results of 1534 frozen sections of thyroid specimens analyzed over
      the 11-year period from 1995 through 2005 and their correlations with the final
      histological examination. Deferred responses were not taken into account for
      statistical calculations. RESULTS: In our series, frozen-section diagnosis was
      concordant with subsequent histopathological examination in 92% of cases,
      discordant in 3%, and deferred in 5%. The global specificity of frozen section
      analysis for all histological subtypes was 99.8% and its sensitivity 67%. Its
      sensitivity for thyroid cancer was lower in follicular (42%) and papillary
      carcinoma (64%) than medullary (100%), anaplastic (100%), secondary (100%), mixed
      (100%), and insular carcinomas (86%). CONCLUSION: In our series, as in the
      literature, most of the discordances between frozen-section and definitive
      diagnosis were associated with microfollicular lesions, which explain the low
      sensitivity of 67%. Our results demonstrate the reliability of intraoperative
      frozen-section analysis in thyroid surgery. Collaboration between pathologists,
      radiologists, and clinicians should be emphasized.

PMID- 18329239
TI  - [Spontaneous hepatic hyperdensity].

PMID- 18329240
TI  - [Impact of adverse events on the practices of 15 general practitioners].
AB  - INTRODUCTION: General practitioners are sometimes faced with adverse events,
      which we define here as "all untoward or unfortunate events occurring
      unintentionally during the provision of health care services, but also all such
      events related to any kind of intervention during care." While their social,
      economic, and health repercussions are often studied, little is known about their
      effects on general practitioners, except perhaps for their legal consequences.
      Our principal objectives here were to study the impact of adverse events
      (including medical errors) on the practices of general practitioners and to study
      their representations of the concepts of adverse events and medical errors.
      METHOD: This qualitative work is based on interviews with 15 general
      practitioners in the Rhone-Alpes region. RESULTS: This study collected 66 real
      situations experienced and identified as adverse events by the subjects. Analysis
      shows that these events had a major impact on these practitioners: they caused
      changes in their procedures for diagnosis and treatment, had sometimes important
      psychological consequences, induced them to participate in targeted continuing
      education, and increased their awareness of the legal aspects of some practices,
      including, for example, record-keeping. Most expressed a need to discuss these
      situations, especially in peer groups. CONCLUSION: It appears essential to study
      adverse events and professional practices in primary care and to facilitate their
      ongoing study, especially in the area of family care.

PMID- 18329241
TI  - [Specificity of acne in women older than 25 years].
AB  - INTRODUCTION: Our aim was to examine the specific clinical and therapeutic
      characteristics of acne in women seen in our practice. PATIENTS AND METHODS: This
      retrospective observational study included all women older than 25 years seen in
      our practice between 1 January 2001 and 31 December 2003. RESULTS: The mean age
      of the 79 women included in the study was 31.8 years; 67% reported a family
      history of acne; 79% reported at least one acne-promoting factor, 62% regular
      cosmetic use. Acne began at a mean age of 16.6 years, and only 13% had lesions
      before menarche. Before referral, they had received an average of 2.3+/-1.6
      systemic treatments and 43% had already been treated by isotretinoin. Over an
      average follow-up period of 11 months, 83% of those for whom we prescribed
      isotretinoin had complete remissions, and 17% a partial response. CONCLUSION:
      Acne in women seems to be a persistent form of juvenile acne. Most of the cases
      we saw were inflammatory acne, with extrafacial lesions in one third of cases.
      The high frequency of familial history and severe seborrhea suggest a genetic
      factor. We also noticed the influence of the premenstrual period, stress, sun
      exposure and cosmetic use. Isotretinoin treatment produced the best therapeutic
      response.

PMID- 18329242
TI  - [Management of cancer-related fatigue].
AB  - INTRODUCTION: Cancer-related fatigue is very common but its management remains
      frustrating. We thus sought to review current knowledge in this field:
      epidemiologic data, pathophysiological mechanisms, assessment, and treatment.
      METHODS: We queried the Medline database for all articles on this topic published
      between 1997 and 2007 and analyzed the articles published in English and French,
      as well as some of the essential earlier work. RESULTS: Approximately 60 to 96%
      of patients treated for cancer report fatigue. The prevalence of fatigue that
      persists after the disease is considered to be in remission is substantial.
      Fatigue is a multidimensional problem with biological, psychological, social, and
      personal aspects. Physical causes must be systematically considered
      (comorbidities, anemia, and endocrine disorders), but most cases remain
      unresolved. Many may be attributed to deconditioning. There is not now any
      pharmacological therapy that treats this symptom effectively. Some
      psychostimulants are being tested, but the initial results of the studies are
      contradictory. Exercise is the intervention for which there is the most evidence
      of effectiveness. CONCLUSION: Cancer-related fatigue is a very common symptom for
      which no specific cause can usually be identified. In this situation, rest may be
      more harmful than exercise.

PMID- 18329243
TI  - Superantigens SPEA and SMEZ do not affect secretome expression in Streptococcus
      pyogenes.
AB  - The superantigens, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal
      enterotoxin B (SEB), were recently reported to repress global exoprotein
      synthesis in Staphylococcus aureus. To investigate if this phenomenon could be
      observed in a different Gram-positive pathogen, the effects of two major
      Streptococcus pyogenes superantigens on streptococcal secretome expression were
      examined. Using mutagenesis and genetic complementation, we demonstrated that
      neither streptococcal pyrogenic exotoxin A (SPEA) nor streptococcal mitogenic
      exotoxin Z (SMEZ) had any consistent effect on global protein expression or on
      transcription of genes encoding the secreted exoproteins, DNase B, SPEB and SPEG.
      In S. pyogenes, superantigen production does not appear to have a major
      regulatory role.

PMID- 18329244
TI  - Tetrabromobisphenol A (TBBPA), induces cell death in TM4 Sertoli cells by
      modulating Ca2+ transport proteins and causing dysregulation of Ca2+ homeostasis.
AB  - Tetrabromobisphenol A (TBBPA) is a commonly used brominated flame retardant (BFR)
      utilized to reduce the flammability of a variety of products. Studies have
      indicated that a number of BFRs are becoming widely distributed within the
      environment and are bio-accumulating within organisms. There has been much
      speculation that a variety of phenolic pollutants (including compounds chemically
      related to TBBPA, such as bisphenol A) may cause endocrine disruption and Ca2+
      dysregulation in cells involved in spermatogenesis. In this study we therefore
      investigate the effects of TBBPA on mouse TM4 Sertoli cells (essential for sperm
      development). Results show that TBBPA increases Ca2+ within these cells in the 5
      60 microM concentration range (EC50, 21 microM). TBBPA also causes cell death
      (LC50, 18 microM) partly via apoptosis, involving Ca2+-dependent mitochondrial
      depolarisation. Studies on intracellular Ca2+ transporters shows that TBBPA can
      inhibit sarcoplasmic/endoplasmic reticulum Ca2+-ATPases (SERCA) at low
      concentrations (IC50, 0.4 to 1.2 microM) and also activate the Ryanodine receptor
      Ca2+ channel within the 0.4-4 microM concentration range. Therefore these studies
      suggest that the cytotoxic effects of TBBPA on cells is partly due to
      dysregulation of Ca2+ signalling, by directly affecting Ca2+ transport proteins.

PMID- 18329245
TI  - ZFAT expression in B and T lymphocytes and identification of ZFAT-regulated
      genes.
AB  - The human ZFAT gene encodes a 1243-amino-acid protein containing one AT hook and
      18 C2H2 zinc finger domains, which are highly conserved among ZFAT orthologues
      from fish to mammalian species. Consistent with the presence of multiple
      predicted nuclear localization signals, endogenous ZFAT protein was found to be
      localized to the nucleus. In the mouse tissues examined by Western blotting, ZFAT
      was found to be expressed in thymus, spleen, and lymph nodes, but not in other
      tissues, including bone marrow. Furthermore, ZFAT protein was found to be up
      regulated during the transition from CD4(-)CD8(-) to CD4(+)CD8(+) thymocytes and
      to be expressed only in B and T lymphocytes in peripheral lymphoid tissues.
      Expression array analyses demonstrated that genes that are down-regulated upon
      ZFAT overexpression in mouse Ba/F3 cells are significantly enriched for those
      functionally related to immune responses. These results suggest that ZFAT
      functions as a critical transcriptional regulator in B and T lymphocytes.

PMID- 18329246
TI  - Sleep-wake behavior and responses to sleep deprivation of mice lacking both
      interleukin-1 beta receptor 1 and tumor necrosis factor-alpha receptor 1.
AB  - Data indicate that interleukin (IL)-1 beta and tumor necrosis factor-alpha
      (TNFalpha) are involved in the regulation of non-rapid eye movement sleep
      (NREMS). Previous studies demonstrate that mice lacking the IL-1 beta type 1
      receptor spend less time in NREMS during the light period, whereas mice lacking
      the p55 (type 1) receptor for TNFalpha spend less time in NREMS during the dark
      period. To further investigate roles for IL-1 beta and TNFalpha in sleep
      regulation we phenotyped sleep and responses to sleep deprivation of mice lacking
      both the IL-1 beta receptor 1 and TNFalpha receptor 1 (IL-1R1/TNFR1 KO). Male
      adult mice (IL-1R1/TNFR1 KO, n=14; B6129SF2/J, n=14) were surgically instrumented
      with EEG electrodes and with a thermistor to measure brain temperature. After
      recovery and adaptation to the recording apparatus, 48 h of undisturbed baseline
      recordings were obtained. Mice were then subjected to 6h sleep deprivation at
      light onset by gentle handling. IL-1R1/TNFR1 KO mice spent less time in NREMS
      during the last 6h of the dark period and less time in rapid eye movement sleep
      (REMS) during the light period. There were no differences between strains in the
      diurnal timing of delta power during NREMS. However, there were strain
      differences in the relative power spectra of the NREMS EEG during both the light
      period and the dark period. In addition, during the light period relative power
      in the theta frequency band of the REMS EEG differed between strains. After sleep
      deprivation, control mice exhibited prolonged increases in NREMS and REMS,
      whereas the duration of the NREMS increase was shorter and there was no increase
      in REMS of IL-1R1/TNFR1 KO mice. Delta power during NREMS increased in both
      strains after sleep deprivation, but the increase in delta power during NREMS of
      IL-1R1/TNFR1 KO mice was of greater magnitude and of longer duration than that
      observed in control mice. These results provide additional evidence that the IL-1
      beta and TNFalpha cytokine systems play a role in sleep regulation and in the
      alterations in sleep that follow prolonged wakefulness.

PMID- 18329247
TI  - Deficit of endogenous spatial orienting of attention in children with benign
      epilepsy with centrotemporal spikes (BECTS).
AB  - Attention difficulties have been reported in children with benign epilepsy with
      centrotemporal spikes (BECTS) but have not yet been fully specified. The aim of
      this study was to evaluate the functions of exogenous and endogenous spatial
      orienting of attention and alerting in these children. Two versions of the
      spatial cueing paradigm and an alerting task, including trials with and without
      warning signal, were performed by 25 children with BECTS aged 6-12 years and 25
      controls matched for age, gender and IQ. In these three tasks, patients were
      slower and made more omissions than controls. The alert effect amplitude was
      comparable in both groups at the longer SOAs (450 ms and 800 ms) while, at the
      shortest SOA (100 ms), it was greater in controls than in the BECTS group. In the
      first version of the spatial cueing task (peripheral cues and no probability
      information), the validity effect amplitude, measured by longer response times
      (RTs) in invalid trials compared to valid trials, was comparable in both groups.
      In the second version (central cues and a 75% probability that the target would
      appear at the cued location), the validity effect was larger in the BECTS group
      compared to controls because of a higher cost of invalid trials compared to
      neutral trials. These results suggest the existence of impairments in the
      endogenous orienting of attention in children with BECTS, in particular an
      attention disengagement deficit, while exogenous orienting of attention appears
      to be preserved.

PMID- 18329248
TI  - A polymorphism of the metabotropic glutamate receptor mGluR7 (GRM7) gene is
      associated with schizophrenia.
AB  - INTRODUCTION: Glutamate dysfunction has been implicated in the pathophysiology of
      schizophrenia. The metabotropic glutamate receptors (mGluRs) are G-protein
      coupled receptors. GRM7, the gene that encodes mGluR7, is expressed in many
      regions of the human central nervous system. The GRM7 gene is located on human
      chromosome 3p26, which has been suggested by linkage analysis to contain a
      susceptibility locus for schizophrenia. METHODS: We screened for mutations in all
      exons, exon/intron junctions, and promoter regions of the GRM7 gene in Japanese
      patients with schizophrenia and evaluated associations between the detected
      polymorphisms and schizophrenia. We examined the influence of one polymorphism
      associated with schizophrenia on the expression of GRM7 by dual-luciferase assay
      in transfected cells. RESULTS: Twenty-five polymorphisms/mutations were detected
      in GRM7. Case-control analysis revealed a potential association of a synonymous
      polymorphism (371T/C, rs3749380) in exon 1 with schizophrenia in our case-control
      study of 2293 Japanese patients with schizophrenia and 2382 Japanese control
      subjects (allelic p=0.009). Dual-luciferase assay revealed suppression of
      transcription activity by exon 1 containing this polymorphism and a statistically
      significant difference in the promoter activity between the T and C alleles.
      CONCLUSIONS: Our results support the possible association of a GRM7 gene
      polymorphism with genetic susceptibility to schizophrenia.

PMID- 18329249
TI  - Clinical association of serum interleukin-17 levels in systemic sclerosis: is
      systemic sclerosis a Th17 disease?

PMID- 18329250
TI  - Mutant prevention concentration of ciprofloxacin, enrofloxacin and nalidixic acid
      against Campylobacter jejuni.

PMID- 18329251
TI  - Specialist training in psychiatry in Europe--results of the UEMS-survey.
AB  - According to the aim of the Treaty of Rome from 1957 which postulated the free
      movement of workers throughout the European Union, the European Board of
      Psychiatry in the UEMS (European Union of Medical Specialists) carried out a
      comprehensive survey of training in psychiatry, including all member countries in
      order to evaluate the present state of training in psychiatry in each. The survey
      should indicate whether the training requirements [UEMS Section Psychiatry.
      Charter on training of medical specialists in the EU: requirements for the
      speciality psychiatry. European Archives of Psychiatry and Clinical Neuroscience
      1997;247(Suppl.):S45-7; UEMS Section Psychiatry. Charter on training of medical
      specialists in the EU: requirements for the speciality psychiatry.
      <www.uemspsychiatry.org/board/reports/Chapter6-11.10.03.pdf>; 2003 [last
      revision]] have had an impact on the actual conditions of training in psychiatry
      in the member countries. We gathered 22 questionnaires from 31 national
      representatives involved and 424 questionnaires completed by the chief of
      training and the representative of trainees at the responding training centres
      from 22 countries. The results give an overview about the practice of training in
      psychiatry in many European countries. While there are great differences between
      the training centres in different countries, apparent progress towards developing
      high standards in training in psychiatry has been made.

PMID- 18329252
TI  - Obsessive-compulsive disorder: influence of age at onset on comorbidity patterns.
AB  - PURPOSE: This study investigates the influence of age at onset of OCS on
      psychiatric comorbidities, and tries to establish a cut-off point for age at
      onset. METHODS: Three hundred and thirty OCD patients were consecutively
      recruited and interviewed using the following structured interviews: Yale-Brown
      Obsessive Compulsive Scale; Yale Global Tic Severity Scale and the Structured
      Clinical Interview for DSM-IV. Data were analyzed with regression and cluster
      analysis. RESULTS: Lower age at onset was associated with a higher probability of
      having comorbidity with tic, anxiety, somatoform, eating and impulse-control
      disorders. Longer illness duration was associated with lower chance of having
      tics. Female gender was associated with anxiety, eating and impulse-control
      disorders. Tic disorders were associated with anxiety disorders and attention
      deficit/hyperactivity disorder. No cut-off age at onset was found to clearly
      divide the sample in homogeneous subgroups. However, cluster analyses revealed
      that differences started to emerge at the age of 10 and were more pronounced at
      the age of 17, suggesting that these were the best cut-off points on this sample.
      CONCLUSIONS: Age at onset is associated with specific comorbidity patterns in OCD
      patients. More prominent differences are obtained when analyzing age at onset as
      an absolute value.

PMID- 18329253
TI  - Modifying matrix micro-environmental pH to achieve sustained drug release from
      highly laminating alginate matrices.
AB  - Lamination of alginate matrix tablet at acidic pH can compromise its function as
      a sustained release carrier. This phenomenon is associated with the conversion of
      sodium alginate to alginic acid. An innovative approach for controlling the
      release of a highly water-soluble drug from such matrices is presented in this
      paper. Inclusion of pH-modifiers was employed to raise the micro-environmental pH
      within matrices undergoing dissolution at gastric pH. The changes in micro
      environmental pH of hydrating alginate matrices were visualized with the aid of a
      pH-indicator and subsequently quantified using image analysis. Transient
      elevation in micro-environmental pH impeded alginate protonation and minimized or
      prevented matrix lamination, contributing to preservation of drug diffusion
      barrier. Significant reduction in the rate of drug release at pH 1.2 was achieved
      in the presence of such additives. The action of pH-modifiers was synergistically
      enhanced in the presence of a carbon dioxide barrier formed by effervescing
      sodium bicarbonate, reducing drug release in the acidic medium from 60 to 20%.
      Further insight into the influence of lamination on drug release from alginate
      compacts was given.

PMID- 18329254
TI  - [Acute renal failure in full term neonates with perinatal asphyxia. Prospective
      study of 87 cases].
AB  - BACKGROUND: Renal involvement is frequent in neonates with perinatal asphyxia. It
      is correlated with the severity of neurological damage and seems to worsen the
      long-term neurological outcome. PURPOSE: The aim of this study was to determine
      the incidence of renal failure after perinatal asphyxia, to precise the
      relationship between severity of cerebral damage and renal failure and to
      evaluate the place of renal damage in the short- and middle-term neurological
      outcome. POPULATION AND METHODS: We conducted a prospective study including 87
      full-term neonates admitted in the neonatology department of F. Hached university
      hospital in Sousse (Tunisia) and suffering from hypoxic ischemic encephalopathy
      from 1st January 2003 to 30 June 2005. Renal function was assessed by measuring
      plasma urea and creatinine at age 48 h. Renal failure was defined by a level of
      creatinine above 90 micromol/l. Neurologic examination was performed on day 7.
      The survivors were followed up by the same senior after discharge. RESULTS:
      During the study period, 87 full-term neonates were admitted for hypoxic ischemic
      encephalopathy. The degree of neurological impairment was determined according to
      Sarnat classification: 1st stage 9 neonates (10,3%), 2nd stage 67 (77%) and 3rd
      stage 11(12,6%). Renal failure involved 15 neonates (17,2%) of whom 10 belonging
      to the 2nd stage group. Renal function outcome was favorable in all survivors
      with normalisation of plasma creatinine level between day 5 and day 15. Eight
      neonates died, of whom 3 with renal failure. Neurologic examination was abnormal
      in 36 out of 72 (50%) neonates without renal failure and in 9 of the 12 (75%)
      survivors with renal failure. Among the 12 neonates with renal failure, 7 had
      abnormal neurologic features at discharge. Neurologic assessment between 6 and 18
      months was abnormal in 4/12 (33%) of neonates with renal failure versus 8/72(11%)
      of neonates without renal failure. CONCLUSION: Transient renal failure is
      commonly observed in perinatal asphyxia. Renal failure is correlated with
      neurologic severity. Renal function assessment using creatinine plasma level
      seems to be correlated with neurologic outcome. However, other tools appreciating
      renal function, namely tubular function, should be determined earlier in order to
      predict neurologic outcome after hypoxic ischemic encephalopathy.

PMID- 18329255
TI  - [Surveillance and epidemiology of infant bronchiolitis in France].

PMID- 18329256
TI  - [Juvenile osteoporosis].
AB  - Osteoporosis is induced by a disorder of the bone turnover that generates an
      accelerated destruction process and leads to the rarefaction of the protein
      matrix. The RANK-L/RANK/OPG system is the main actor of the bone remodelling
      regulation. Juvenile osteoporoses may have primary or secondary aetiologies. The
      main causes include constitutional bone fragilities, and osteoporoses, which are
      secondary to chronic inflammatory diseases and sustained steroid treatment.
      Etiologic diagnosis relies on a clinical basis, and is often made too lately when
      complications occur. Osteodensitometry is a sensitive and noninvasive tool for
      measuring mineral bone density in children. The reliability of results is limited
      by the variations due to patients' age, gender, pubertal stage, and by the length
      of bone pieces. The optimal treatment of osteoporosis is preventive, and includes
      accurate nutritional diet, D vitamin-calcium supplementation and regular physical
      activity. Biphosphonates are used for treatment of symptomatic osteoporoses.
      Careful utilization is required in childhood because their late potential
      secondary effects are still unknown. New antiresorptive drugs and other that
      stimulate osteoformation are successfully used in adults. Their effects have not
      been studied in the paediatric population.

PMID- 18329257
TI  - [Evaluation of a screening strategy after occurrence of two simultaneous
      contaminating tuberculosis cases in a pediatric oncology department].
AB  - BACKGROUND: A medical staff and an administrative staff of our paediatric
      oncology department have contracted a pulmonary tuberculosis. This is a rare
      situation and the management of this infection threat in a paediatric oncology
      department is not clearly defined. Recommendations tell we must treat all
      patients. Nevertheless, antituberculosis agent expose to increased toxic effects
      and immunocompromised patients have an increased risk of experiencing progression
      of latent mycobacterium tuberculosis infection to active tuberculosis disease.
      OBJECTIVE: This study aims at the evaluation of a screening and a treatment
      strategy adapted for a paediatric oncology department. METHOD: From April 2004 to
      April 2005, 80 children with a solid tumour were screened for tuberculosis
      according to a screening and treatment protocol established by a
      multidisciplinary committee. Two risk groups were defined according to age and
      immunodepression status. The "high risk" group is composed of less than 2 years
      old children and children who underwent an haematological peripheral stem cell
      transplantation. All other children were included in the "low risk" group. The
      screening was based on clinical, biological and radiological data performed three
      times spaced out by 2 or 3 months. At the end of each part of screening, the
      multidisciplinary committee analyzed the results and discussed the utility of an
      antituberculosis treatment. RESULTS: 80 children (31 boys and 49 girl) with a
      median age of 7,3 years (0,3-24) participated to the screening. Sixty children
      were still undergoing anticancer treatments. Twenty belonged to the high risk
      group. The complete screening was performed in 32% of the patients. Three
      antituberculosis' treatment were initiated: 2 for prophylaxis purpose and 1 for a
      tuberculosis prime-infection. A child had an additional check-up because of an
      abnormal chest X-ray. Our management strategy allowed us to treat significantly
      less patients when compared to national guidelines (3 vs 80 test Chi-2 p<0.001).
      No side effects of antituberculosis agents were noted. No tuberculosis has been
      observed in our population 28 months after the completion of the treatment.
      CONCLUSION: The proposed screening allowed us to treat a minimum of children and
      thus, to reduce the potential toxicity induced by antituberculosis' treatments.

PMID- 18329258
TI  - The accuracy of cancer diagnoses as reported in families with head and neck
      cancer: a case-control study.
AB  - AIMS: The assessment of the risk of developing cancer is largely based on family
      history. This study aimed to confirm as many cancer diagnoses as possible in
      families of patients with second primary tumours after index squamous cell
      carcinoma of the head, single squamous cell carcinoma and spouse controls.
      MATERIALS AND METHODS: Eighty patients with second primary tumours, 67 with
      single squamous cell carcinoma and 47 spouse controls were recruited into the
      study. A detailed interview was undertaken on all study participants, including
      information on all first-degree relatives for causes of death and possible
      diagnoses of cancer. RESULTS: Details were available from 1340 first-degree
      relatives: second primary tumour group 570 relatives, single squamous cell
      carcinoma 429 relatives and the spouse controls 341 relatives. There were 174
      cases of cancer (76, 56 and 42, respectively). For those relatives that had died,
      submissions were made to the Office of National Statistics to confirm the cause
      and date of death. One hundred and thirty-three cases were submitted for Office
      of National Statistics flagging (58, 42 and 33, respectively). Seventy-four of
      the first-degree relatives with cancer were successfully traced. Tracing
      confirmed a cancer diagnosis but no further details of the primary site in 31 of
      the relatives. Thirty-eight of the first-degree relatives were confirmed to have
      the cancer site of diagnosis reported by the study participants. Thirteen of the
      reported diagnoses in the first-degree relatives were inaccurate with regard to
      the cancer site of origin. Five of the first-degree relatives did not have a
      cancer diagnosis confirmed on the death certificate. CONCLUSIONS: This study
      highlights the difficulties encountered in confirming cancer diagnoses among
      first-degree relatives within this cancer site. To improve such studies and our
      routine collection of data within the clinic setting, more robust systems are
      needed to interlink cancer registries, population data and hospital records.

PMID- 18329259
TI  - An update on a case of regression of lung metastases after radiotherapy for bone
      metastasis in renal cell carcinoma.

PMID- 18329260
TI  - Lateral line nerve fibers do not code bulk water flow direction in turbulent
      flow.
AB  - The discharges of anterior and posterior lateral line nerve afferents were
      recorded while stimulating goldfish, Carassius auratus, with bulk water flow.
      With increasing flow velocity lateral line afferents increased their discharge
      rates. However, an increased response to flow rates occurred even if flow
      direction was reversed. Thus, individual lateral line afferents did not encode
      the direction of running water. Frequency spectra of the water motions quantified
      with particle image velocimetry revealed flow fluctuations that increased with
      increasing flow velocity. Maximal spectral amplitudes of the flow fluctuations
      were below 5 Hz (bulk flow velocity 4-15 cms(-1)). The frequency spectra of the
      firing rates of lateral line afferents also showed an increase in amplitude when
      fish were exposed to running water. The maximal spectral amplitudes of the
      recorded data were in the frequency range 3-8 Hz. This suggests that the lateral
      line afferents mainly responded to the higher frequency fluctuations that
      developed under flow conditions, but not to the direct current flow or the lower
      frequency fluctuations. Although individual lateral line afferents encoded
      neither flow velocity nor flow direction we suggest that higher order lateral
      line neurons can do so by monitoring flow fluctuations as they move across the
      surface of the fish.

PMID- 18329261
TI  - Association of fish and long-chain n-3 polyunsaturated fatty acid intakes with
      the occurrence of depressive episodes in middle-aged French men and women.
AB  - This study aimed to seek whether habitual fish and seafood or n-3 long-chain PUFA
      intake could influence the occurrence of depressive episodes. In a subsample from
      the French SU.VI.MAX cohort, dietary habits have been assessed during the first 2
      years of the follow-up (six 24-h records) and declarations of antidepressant
      prescription, taken as markers of depressive episodes, have been recorded during
      the 8-year follow-up. Subjects consuming fatty fish or with an intake of long
      chain n-3 PUFA higher than 0.10% of energy intake had a significantly lesser risk
      of any depressive episode and of recurrent depressive episodes, but not of single
      depressive episode. These associations were stronger in men and in non-smokers.
      In contrast, smokers eating fatty fish had an increased risk of recurrent
      depression. These results suggest that a usual intake of fatty fish or long-chain
      n-3 PUFA may decrease the risk of recurrent depression in non-smokers.

PMID- 18329262
TI  - Centralization of dairy farming facilities for improved economics and
      environmental quality.
AB  - In Japan, most farm animal excreta has been stored directly on farmland. Runoff
      from this storage has often caused water pollution. Biogasification is
      anticipated as an important technology to manage excreta properly, but complex
      problems hinder its introduction. Economic aspects of management have been
      especially difficult for dairy farmers. For this study, structural problems
      regarding introduction of biogasification into dairy farming were identified.
      Subsequently, a desirable system of dairy farming including biogasification was
      suggested, and an evaluation model of the financial balance was constructed. A
      case study using current financial balances of several systems of dairy farming
      was evaluated using the constructed model and actual data. The systems were based
      on several policy alternatives including the suggested system mentioned above.
      Results show that a farmer can obtain sufficient income from a system featuring
      centralization of dairy housing and biogasification facilities and coordinated
      management by over six farmers.

PMID- 18329263
TI  - Extractability and leachability of heavy metals in Technosols prepared from
      mixtures of unconsolidated wastes.
AB  - Mixtures of wastes were prepared to improve on the characteristics of the
      individual ingredients as Technosols, with special attention given to heavy metal
      extractability. An anaerobic digested sewage sludge and a CaO-treated aerobic
      sludge were used. A mixture of the two sludges (50:50 DW basis) was also prepared
      to provide a third type of sludge. The residues were mixed with other types of
      waste, such as fly ash, Linz-Donowitz slag, foundry sand, shot blasting machine
      scrap, fettling and barley straw. Extractability of Cu, Cr, Ni, and Zn by 0.01 M
      CaCl(2) extraction (Me(CACI(2)) was carried out, and leachability of these
      elements was estimated by acidification of an aqueous suspension of the mixtures
      with 0.5 N acetic acid (Me(acetic)). The total concentrations of the metals were
      also determined (Me(T)). The Me(CACI(2)/Me(T) ratios for Cu and Ni (means: 4.0%
      and 3.1%) were higher than those for Cr and Zn (means: 0.07% each). The mean
      Me(acetic)/Me(T) ratios followed the order Ni, Zn, Cu, and Cr (19.5%, 4.1%, 3.7%,
      and 0.09%, respectively). The results highlight the existence of complex
      interactions among organic matter solubility, pH and heavy metal extractability.

PMID- 18329264
TI  - Cancer causes and prevention: a condensed appraisal in Europe in 2008.
AB  - The rising cancer burden in Europe, mainly due to a rapidly ageing population,
      demands a clear and coordinated response from researchers, oncologists and other
      physicians, public health professionals and policy-makers. Primary and secondary
      prevention is the front line in the complex battle against cancer in Europe. To
      formulate the best strategies in this fight, the major determinants of cancer are
      summarised in the order of their relative importance in Europe, including tobacco
      smoking, alcohol, diet, physical activity, occupational factors, environmental
      factors, infectious agents and genetic and hormonal factors. Furthermore, this
      paper offers explicit recommendations on individual behaviour modification and
      possible public policies. It also details the numerous examples of European
      policies and programmes already in effect which aim to reduce the impact of these
      risk factors on cancer. Although there are still pending questions, which need
      further epidemiologic research, it is also true that we have more operational
      knowledge for cancer prevention than ever before. The prompt implementation of
      prevention programmes such as those detailed here should be applied with
      determination to maximise the prevention results.

PMID- 18329265
TI  - Brain microglia express steroid-converting enzymes in the mouse.
AB  - In the CNS, steroid hormones play a major role in the maintenance of brain
      homeostasis and it's response to injury. Since activated microglia are the
      pivotal immune cell involved in neurodegeneration, we investigated the
      possibility that microglia provide a discrete source for the metabolism of active
      steroid hormones. Using RT-PCR, our results showed that mouse microglia expressed
      mRNA for 17beta-hydroxysteroid dehydrogenase type 1 and steroid 5alpha-reductase
      type 1, which are involved in the metabolism of androgens and estrogens.
      Microglia also expressed the peripheral benzodiazepine receptor and steroid acute
      regulatory protein; however, the enzymes required for de novo formation of
      progesterone and DHEA from cholesterol were not expressed. To test the function
      of these enzymes, primary microglia cultures were incubated with steroid
      precursors, DHEA and AD. Microglia preferentially produced delta-5 androgens
      (Adiol) from DHEA and 5alpha-reduced androgens from AD. Adiol behaved as an
      effective estrogen receptor agonist in neuronal cells. Activation of microglia
      with pro-inflammatory factors, LPS and INFgamma did not affect the enzymatic
      properties of these proteins. However, PBR ligands reduced TNFalpha production
      signifying an immunomodulatory role for PBR. Collectively, our results suggest
      that microglia utilize steroid-converting enzymes and related proteins to
      influence inflammation and neurodegeneration within microenvironments of the
      brain.

PMID- 18329266
TI  - Effect of temperature on the efficiency of the thermo- and mesophilic aerobic
      batch biodegradation of high-strength distillery wastewater (potato stillage).
AB  - The objective of the study was to assess the effect of temperature on the extent
      of aerobic batch biodegradation of potato stillage with a mixed culture of
      bacteria of the genus Bacillus. The experiments were performed in a 5-l stirred
      tank reactor at 20, 30, 35, 40, 45, 50, 55, 60, 63 and 65 degrees C with the pH
      of 7. Only at 65 degrees C, no reduction in chemical oxygen demand (COD) was
      found to occur. Over the temperature range of 20-63 degrees C, the removal
      efficiency was very high (with an extent of COD reduction following solids
      separation that varied between 77.57% and 89.14% after 125 h). The process ran at
      the fastest rate when the temperature ranged from 30 to 45 degrees C; after 43 h
      at the latest, COD removal amounted to 90% of the final removal efficiency value
      obtained for the process. At 20, 55, 60 and 63 degrees C, a 90% removal was
      attained after 80 h. Two criteria were proposed for the identification of the
      point in time when the process is to terminate. One of these consists in
      maximising the product of the extent of COD reduction and the extent of N-NH4
      content reduction. The other criterion is a simplified one and involves the
      search for the minimal value of N-NH4 concentration.

PMID- 18329267
TI  - Identification of novel series of human CCR1 antagonists.
AB  - A hit-to-lead optimization process was carried out on the high throughput
      screening hit compound 1 resulting in the identification of several potent and
      selective CCR1 receptor antagonists. Compound 37 shows the best overall profile
      with IC(50) values of <100 nM in binding and functional assays.

PMID- 18329268
TI  - Targeting gastrin-releasing peptide receptors of prostate cancer cells for
      photodynamic therapy with a phthalocyanine-bombesin conjugate.
AB  - Sulfonated aluminum phthalocyanines (AlPcS) are potent photosensitizers for the
      photodynamic therapy (PDT) of cancer. In this study we evaluate the possibility
      to improve the efficacy of AlPcS-PDT for prostate cancer by targeting
      tetrasulfonated aluminum phthalocyanines (AlPcS(4)) to the gastrin-releasing
      peptide receptor (GRPR) through coupling to bombesin. A mono-carbohexyl
      derivative of AlPcS(4) is attached to 8-Aoc-bombesin(7-14)NH(2) via an amide
      bridge to yield a bombesin-AlPcS(4) conjugate linked by a C-14 spacer chain. The
      conjugate is characterized by mass spectroscopy and shown to bind to the GRPR
      with a relative binding affinity (RBA) of 2.3, taking bombesin (RBA=100) as
      unity. The in vitro photodynamic efficacy of the conjugate against PC-3 human
      prostate cancer cells is improved by a factor 2.5 over the non-conjugated mono
      carbohexyl derivative of AlPcS(4).

PMID- 18329269
TI  - Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor
      antagonists.
AB  - A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is
      described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM),
      selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat
      haloperidol-induced catalepsy model for Parkinson's disease.

PMID- 18329270
TI  - The effect of backpack heaviness on trunk-lower extremity muscle activities and
      trunk posture.
AB  - The purpose of the present study is to analyze trunk-lower extremity muscle
      activities and trunk postural changes during the carriage of different backpacks.
      Nineteen male university students (21+/-3 years) participated in the experiment's
      four standing modes: (1) unloaded standing, (2) 10% body weight (BW) load (in the
      form of a backpack), (3) 15% BW load and (4) 20% BW load. Bilateral rectus
      abdominis, erector spinae, vastus medialis and biceps femoris muscle activities
      were recorded using surface electromyography (SEMG), while trunk inclination,
      side flexion and rotation were measured by using VICON 250 during all standing
      modes. The results showed that rectus abdominis muscle activities increased
      progressively and disproportionably as the backpack load increased. As for the
      trunk posture, almost the same backward inclination was adapted even with
      increasing backpack heaviness. Twenty percent BW backpack causes the most
      significant muscular and postural changes so it should be avoided. However, it is
      recommended to study other backpack factors such as frequency of usage, usage
      time, type of the backpack and age to come up with a complete usage
      recommendation.

PMID- 18329271
TI  - Between-day repeatability of knee kinematics during functional tasks recorded
      using flexible electrogoniometry.
AB  - The objective of this study was to assess the between-day repeatability of knee
      kinematics during activities of daily living recorded by electrogoniometry. One
      rater assessed the peak knee angles and knee excursion of 15 subjects during 13
      activities twice with an average of 22 days (range 5-31) between the two
      assessments. The 15 subjects included four patients one year after total knee
      replacement (TKR) surgery, five patients before TKR surgery and six age-matched
      controls. Intra-class correlation coefficients and Bland and Altman coefficient
      of repeatability were derived to analyse the results. Only the most affected leg
      of the patients and the right leg of the controls were used for analysis.
      Different measures of repeatability showed different results. Intra-class
      correlation coefficients were higher than 0.75 for peak values of all functions
      except sitting down and rising from a standard chair. However, coefficients of
      repeatability ranged from 5.6 degrees for the loading response in level walking
      to 39.8 degrees for stepping out of a bath. Both of these values are higher than
      clinically significant changes seen after total knee surgery. It was concluded
      that for a single assessment on individual patients, the functional knee motion
      as performed in this study did not have sufficient repeatability. However, if the
      measurements are used to assess the average changes before and after surgery in a
      group of patients, the assessment of knee motion during activities such as level
      walking, and slope and stair ascending and descending were found to be
      sufficiently repeatable.

PMID- 18329272
TI  - Design, synthesis, and evaluation of trifluoromethyl ketones as inhibitors of
      SARS-CoV 3CL protease.
AB  - A series of trifluoromethyl ketones as SARS-CoV 3CL protease inhibitors was
      developed. The inhibitors were synthesized in four steps from commercially
      available compounds. Three different amino acids were explored in the P1-position
      and in the P2-P4 positions varying amino acids and long alkyl chain were
      incorporated. All inhibitors were evaluated in an in vitro assay using purified
      enzyme and fluorogenic substrate peptide. One of the inhibitors showed a time
      dependent inhibition, with a K(i) value of 0.3 microM after 4h incubation.

PMID- 18329273
TI  - Novel inhibitors of 17beta-hydroxysteroid dehydrogenase type 1: templates for
      design.
AB  - The 17beta-hydroxysteroid dehydrogenases (17beta-HSDs) catalyze the
      interconversion between the oxidized and reduced forms of androgens and estrogens
      at the 17 position. The 17beta-HSD type 1 enzyme (17beta-HSD1) catalyzes the
      reduction of estrone (E1) to estradiol and is expressed in malignant breast
      cells. Inhibitors of this enzyme thus have potential as treatments for hormone
      dependent breast cancer. Syntheses and biological evaluation of novel non
      steroidal inhibitors designed to mimic the E1 template are reported using
      information from potent steroidal inhibitors. Of the templates investigated
      biphenyl ethanone was promising and led to inhibitors with IC(50) values in the
      low micromolar range.

PMID- 18329274
TI  - Identification of neomycin B-binding site in T box antiterminator model RNA.
AB  - The T box transcription antitermination mechanism regulates the expression of
      unique genes in many Gram-positive bacteria by responding, in a magnesium
      dependent manner, to uncharged cognate tRNA base pairing with an antiterminator
      RNA element and other regions of the 5'-untranslated region. Model T box
      antiterminator RNA is known to bind aminoglycosides, ligands that typically bind
      RNA in divalent metal ion-binding sites. In this study, enzymatic footprinting
      and spectroscopic assays were used to identify and characterize the binding site
      of neomycin B to an antiterminator model RNA. Neomycin B binds the antiterminator
      bulge nucleotides in an electrostatic-dependent manner and displaces 3-4
      monovalent cations, indicating that the antiterminator likely contains a divalent
      metal ion-binding site. Neomycin B facilitates rather than inhibits tRNA binding
      indicating that bulge-targeted inhibitors that bind the antiterminator via non
      electrostatic interactions may be the more optimal candidates for antiterminator
      targeted ligand design.

PMID- 18329275
TI  - A small molecule inhibitor of alpha4 integrin-dependent cell migration.
AB  - A small molecule inhibitor of alpha4 integrin-dependent cell migration was
      identified through a cell-based screen of small molecule libraries. Biochemical
      and cellular experiments suggest that this molecule functions by interacting with
      gamma-parvin. This molecule should serve as a useful tool to study alpha4
      integrin signaling and may lead to new therapeutics for the treatment of
      autoimmune diseases.

PMID- 18329276
TI  - Design and synthesis of novel leucomycin analogues modified at the C-3 position.
      Part II: 3-O-(3-Aryl-2-propenyl)leucomycin analogues.
AB  - The design and synthesis of 16-membered macrolides modified at the C-3 position
      are described. Starting from fully protected intermediate (5), appropriate
      modifications including Heck reaction were performed to furnish 3-O-(3-aryl-2
      propenyl)leucomycin A(7) analogues (9a-9m). These leucomycin A(7) derivatives
      showed improved in vitro antibacterial activities against clinically important
      pathogens including erythromycin-resistant Streptococcus pneumoniae (ERSP). SAR
      analysis of derivatives modified at the C-3 and C-3'' positions suggested that
      single modification at C-3 or C-3'' was effective for in vitro antibacterial
      activity.

PMID- 18329277
TI  - Algorithm for analysis of OJDIP fluorescence induction curves in terms of photo-
      and electrochemical events in photosystems of plant cells: derivation and
      application.
AB  - The algorithm for simulation of the OJDIP fluorescence induction curve in
      chloroplasts under variable conditions is presented. It is derived from analyzes
      of chlorophyll a fluorescence kinetics upon excitation with single- (STF), twin-
      (TTF) and repetitive STF excitations, and from the rate equations that describe
      the sequence of transfer steps associated with the reduction of the primary
      quinone acceptor Q(A) and the release of photochemical fluorescence quenching of
      photosystem II (PSII) in multi-turnover excitation (MTF). The fluorescence
      induction algorithm (FIA) considers a photochemical O-J-D, a photo
      electrochemical J-I and an I-P component (phase) which probably is associated
      with a photo-electric interaction between PSI and PSII. The photochemical phase
      incorporates the kinetics associated with the double reduction of the acceptor
      pair [PheQ(A)] in Q(B)-nonreducing reaction centers (RCs) and the associated
      doubling of the variable fluorescence, in agreement with the three-state trapping
      model (TSTM) of PSII. Application of and results with the algorithm are
      illustrated for MTF-induced OJDIP curves, measured in dark-adapted, in STF pre
      excited and in DCMU inhibited thylakoids.

PMID- 18329278
TI  - Peripheral nerve damage associated with administration of taxanes in patients
      with cancer.
AB  - Peripheral neuropathy is a well recognized toxicity of taxanes, usually resulting
      to dose modification and changes in the treatment plan. Taxanes produce a
      symmetric, axonal predominantly sensory distal neuropathy with less prominent
      motor involvement. A "dying back" process starting from distal nerve endings
      followed by effects on Schwann cells, neuronal body or axonal transport changes
      and a disturbed cytoplasmatic flow in the affected neurons is the most widely
      accepted mechanism of taxanes neurotoxicity. The incidence of taxanes-induced
      peripheral neuropathy is related to causal factors, such as single dose per
      course and cumulative dose and risk factors including treatment schedule, prior
      or concomitant administration of platinum compounds or vinca alcaloids, age and
      pre-existing peripheral neuropathy of other causes. The most reliable method to
      assess taxanes neurotoxicity is by clinical examination combined with
      electrophysiological evaluation. There is currently no effective symptomatic
      treatment for paclitaxel-associated pain, myalgias and arthralgias. Tricyclic
      antidepressants and anticonvulsants have been used as symptomatic treatment of
      neurotoxicity with some measure of success. Therefore, new approaches for
      prophylaxis against taxanes-induced peripheral neuropathy are needed. Several
      neuroprotective agents including, thiols, neurotrophic factors, and antioxidants
      hold promise for their ability to prevent neurotoxicity resulting from taxanes
      exposure. However, further confirmatory trials are warranted on this important
      clinical topic. This review critically looks at the pathogenesis, incidence, risk
      factors, diagnosis, characteristics and management of taxanes-induced peripheral
      neuropathy. We also highlight areas of future research.

PMID- 18329279
TI  - Metabolic programming in the immediate postnatal period.
AB  - In recent decades, there has been a dramatic increase in the incidence of obesity
      in all age groups of the population in the USA. In addition to genetics and life
      style changes, the important role of metabolic programming effects in the
      etiology of the obesity epidemic is being increasingly recognized. Although the
      role of a compromised intrauterine environment in fetal metabolic programming is
      well documented to contribute to the development of adult-onset diseases,
      vulnerability in the immediate postnatal period to similar conditions has also
      been shown. Metabolic programming effects induced by altered nutritional
      experiences in the immediate postnatal period can give rise to long-term
      consequences in the context of the current obesity epidemic.

PMID- 18329280
TI  - Preparing offspring for future conditions is adaptive.

PMID- 18329281
TI  - Differential regulation of the interferon induced gene ISG12A by serum from
      healthy and preeclamptic pregnancies.
AB  - Endothelial-cell dysfunction is central in the preeclamptic pathogenesis. Several
      components present in the blood of the preeclamptic mother are capable of
      mediating this dysfunction. We analyzed the regulation of the ISG12A gene by
      serum from the third trimester, to elucidate the role of type 1 interferon ISGs
      late in both healthy and preeclamptic pregnancies. The ISG12A transcription was
      up-regulated by serum from healthy pregnant women, but not by preeclamptic serum
      in HeLa and human umbilical vein endothelial cells (HUVEC). However, the ISG12A
      up-regulation by healthy pregnancy serum was not due to a general type 1
      interferon response, since 6-16 and OAS1 were not up-regulated similarly. Also,
      the up-regulation of ISG12A was independent of the interferon-alpha receptor 2,
      but dependent on STAT1. Stimulation with folic acid alone or in combination with
      preeclamptic serum up-regulated ISG12A and 6-16. We conclude that type 1
      interferon is not increased in third trimester serum, neither from healthy nor
      preeclamptic pregnancies. However, since ISG12A mRNA is up-regulated in healthy
      pregnancies, the ISG12A protein might take part in maintaining endothelial
      stability, as this function is lacking in preeclamptic pregnancies. Folic acid
      may ameliorate endothelial cell stability in preeclampsia by up-regulating
      ISG12A.

PMID- 18329282
TI  - Decreased IL-1 RA concentration in ascites is associated with a significant
      improvement in overall survival in ovarian cancer.
AB  - BACKGROUND: Cytokines play a major role in promoting the growth and metastatic
      spread of cancer cells. Interleukin-1 alpha and beta (IL-1) and IL-1 RA are known
      to be critically involved in carcinogenesis and in various solid tumors. There
      are limited data on expression of IL-1 alpha, beta and RA in serum and ascites in
      patients with advanced ovarian cancer. Objectives of this study were to
      investigate the level of IL-1 alpha, IL-1 beta and IL-1 RA in serum and ascites
      from patients with ovarian cancer and their impact on the prognosis. METHODS:
      Fifty-three women with ovarian cancer (OC) (33 patients with primary OC and 20
      with relapsed OC) and 50 women with benign gynaecological diseases as a control
      group (CG) were enrolled onto this prospective study. IL-1 alpha, beta and RA
      levels were analyzed in serum and ascites by ELISA technique. RESULTS: The median
      age was 55 years (range 19-80) in the ovarian cancer group and 40 years (range 15
      89) in the controls. The distribution of histological type of ovarian cancer was
      as follows: serous-papillary 43 (81.1%), 4 (7.5%) mucinous, 3 (5.7%) endometroid
      and 3 (5.7%) clear cell carcinoma. The concentrations of IL-1 beta and RA in
      ascites or peritoneal fluid were significantly increased in patients with OC in
      comparison to the CG, for both cytokines (p<0.0001); also the concentration of IL
      1 RA in serum was increased in OC (p=0.003) vs. CG. An increased level of IL-1
      beta in ascites correlated significantly with a poorer histopathological grading
      (p=0.038). IL-1 RA concentration in ascites was correlated with advanced FIGO
      stage (p=0.049) and the IL-1 RA serum level with ascites volume (< or =500 ml vs.
      >500 ml) (p=0.046). Patients with IL-1 RA level in ascites lower than the cut off
      value of 695.6 pg/ml showed a significant better progression-free median survival
      (24.6 vs. 12.8 months, p=0.008) and postoperative median overall survival (34.6
      vs. 17 months, p=0.01) in comparison to patients with an IL-1 RA level in ascites
      higher than the cut off level. Additionally, a higher expression of IL-1 beta in
      serum (p=0.004) and ascites (p=0.05) reduced significantly the progression-free
      survival. In the multivariate analysis, expression of IL-1 RA in ascites was an
      independent prognostic factor for good progression-free and postoperative overall
      survival (HR, 0.39 95% CI, 0.18-0.83, p=0.01, HR, 0.36 95% CI, 0.16-0.8, p=0.01).
      CONCLUSIONS: IL-1 RA levels in ascites lower than the cut off value of 695.6
      pg/ml are associated with a significant improvement in postoperative and
      progression-free survival. IL-1 RA shows a prognostic relevance in ovarian
      cancer.

PMID- 18329283
TI  - The topical application of nerve growth factor as a pharmacological tool for
      human corneal and skin ulcers.
AB  - AIM: The nerve growth factor is a soluble protein produced by and acting upon a
      number of different cells located in the nervous, endocrine and immune systems.
      Recent studies have shown that nerve growth factor (NGF) exerts a critical role
      on epithelial cells and fibroblasts under normal and pathological conditions. In
      this review, we present data prospecting the clinical potentiality of NGF in
      cutaneous and ocular "non-healing" chronic ulcers. DATA SYNTHESIS: A consistent
      number of in vitro and in vivo studies carried out on animal models and in humans
      indicated that fibroblasts and epithelial cells are receptive to the action of
      NGF and that NGF promotes skin and cornea ulcer healing. These observations lead
      to the hypothesis that NGF can be a potential useful pharmacological agent for
      clinical investigations. CONCLUSION: The available clinical evidences suggest
      that the topical application of NGF promotes healing action without side effects
      on corneal and cutaneous tissues damaged by chemical, physical and surgical
      insults and autoimmune disorders.

PMID- 18329284
TI  - The hERG K+ channel: target and antitarget strategies in drug development.
AB  - The human ether-a-go-go related gene (hERG) K+ channel is of great interest for
      both basic researchers and clinicians because its blockade by drugs can lead to
      QT prolongation, which is a risk factor for torsades de pointes, a potentially
      life-threatening arrhythmia. A growing list of agents with "QT liability" have
      been withdrawn from the market or restricted in their use, whereas others did not
      even receive regulatory approval for this reason. Thus, hERG K+ channels have
      become a primary antitarget (i.e. an unwanted target) in drug development because
      their blockade causes potentially serious side effects. On the other hand, the
      recent identification and functional characterization of hERG K+ channels not
      only in the heart, but also in several other tissues (e.g. neurons, smooth muscle
      and cancer cells) may have far reaching implications for drug development for a
      possible exploitation of hERG as a target, especially in oncology and cardiology.

PMID- 18329285
TI  - Increased GFR and renal excretory function by activation of TRPV1 in the isolated
      perfused kidney.
AB  - To test the hypothesis that activation of the transient receptor potential
      vanilloid type 1 (TRPV1) channels leads to natriuresis and diuresis via an
      increase in glomerular filtration rate (GFR), recirculating Krebs-Henseleit
      buffer added with inulin was perfused in the isolated perfused kidney of male
      Wistar rat at a constant flow, and perfusion pressures (PPs) were pre-adjusted to
      three different levels ( approximately 100, approximately 150, and approximately
      190mmHg) with phenylephrine. Capsaicin (Cap), a selective TRPV1 agonist, was
      perfused in the presence or absence of capsazepine (Capz), a selective TRPV1
      antagonist, CGRP(8-37), a selective calcitonin gene-related peptide (CGRP)
      receptor antagonist, or spantide II (Spa), a selective substance P (SP) receptor
      antagonist. At the higher (150 and 190mmHg) but not baseline (100mmHg) PP levels,
      Cap at 10microM significantly decreased PP and increased GFR, urine flow rate
      (UFR) and Na+ excretion (UNaV). At the highest (190mmHg) PP level, Cap (2, 10,
      30microM) dose-dependently decreased PP and increased GFR, UFR, UNaV, and the
      release of CGRP and SP. Capz or CGRP(8-37) combined with Spa fully blocked the
      effect of Cap on PP, GFR, UFR, UNaV, and the release of CGRP and SP. In
      conclusion, activation of TRPV1 in the isolated kidney decreases renal PP and
      increases GFR and water/sodium excretion possibly via simultaneous activation of
      CGRP and SP receptors upon their enhanced release, suggesting that TRPV1 plays a
      key role in modulating renal hemodynamics and excretory function.

PMID- 18329286
TI  - Localization and fate of Fgf10-expressing cells in the adult mouse brain
      implicate Fgf10 in control of neurogenesis.
AB  - We used Fgf10-lacZ reporter mice to investigate the distribution and fate of
      Fgf10-expressing cells in the developing and adult mouse brain. We find that the
      domain of Fgf10 expression expands post-natally and new niches emerge in the
      adult brain. Fgf10 is expressed in the adult cerebellum, thalamic, mid- and
      hindbrain nuclei and hippocampal CA fields, as previously reported in the rat
      brain. In addition though, we have discovered expression in: the hippocampal
      dentate gyrus; a discrete trail linking the ventral telencephalon with the
      olfactory bulbs; ventral ependyma of the third ventricle from where cells appear
      to disperse into the hypothalamus; and in the pituitary gland. Most Fgf10
      expressing cells or their immediate descendants appear immature but a subset
      differentiates into neurons and glial cells. The manner in which Fgf10 is
      expressed in these active and quiescent neurogenic niches implicates it in
      control of neurogenesis and/or conservation of neurogenic potential.

PMID- 18329287
TI  - Evaluation of expanded bed adsorption chromatography for extraction of
      prothrombin complex from Cohn Supernatant I.
AB  - This study evaluated the feasibility of substituting expanded bed adsorption
      (EBA) chromatography for an existing chromatographic purification process for the
      isolation of prothrombin complex concentrate (PCC) from Cohn Supernatant I. The
      EBA chromatography (Streamline) resins were compared to the current DEAE
      cellulose resin for the extraction of PCC from Cohn SNI. EBA chromatography
      resins efficiently bound PCC from Cohn SNI at a significantly higher flow rate of
      up to 300 cm/h compared to 30 cm/h for the current DEAE-cellulose process.
      Composition and yield of the recovered PCC reflected the elution conditions used.
      The results indicate that EBA chromatography could be used to efficiently produce
      PCC comparable to existing products.

PMID- 18329288
TI  - Electromyographic activity of sternocleidomastoid muscle in patients with
      Parkinson's disease.
AB  - The aim of this study was to evaluate the effect of administration of levo-dopa,
      which means without effect-off state and under effect-on state, on the
      sternocleidomastoid muscle electromyographic activity (SCM-EA) in patients with
      Parkinson's disease (PD) at rest and to compare it to asymptomatic subjects. Ten
      patients with PD, mean age 64.6+/-6.2 (SD) years and nine asymptomatic subjects,
      mean age 61.4+/-5.9 (SD) years were studied. The SCM-EA was evaluated during
      maximal inspiratory pressure and breathing at rest through surface
      electromyography. Statistical analysis was performed with t-test (anthropometric
      data and SCM-EA of patients in off state to asymptomatic), Mann-Whitney (SCM-EA
      of patients in on state to asymptomatic) and Wilcoxon test (SCM-EA off and on
      states). The effect size index (d) was calculated for statistically significant
      differences. There were no significant differences in SCM electromyographic
      activity between patients with PD comparing off to on (p=0.13) or among on state
      to asymptomatic subjects (p=0.06). However, when subjects with PD in off where
      compared to asymptomatic there was a significantly higher SCM electromyographic
      activity (p=0.03, d=1.09). These patients, without levo-dopa effect, when
      compared with asymptomatic subjects, present a significantly higher
      electromyographic activity of SCM, the main accessory respiratory muscle, which
      could be related to an increased work of breathing.

PMID- 18329289
TI  - Motor learning transiently changes cortical somatotopy.
AB  - Learning a complex motor skill is associated with changes in motor cortex
      representations of trained body parts. It has been suggested that representation
      changes reflect the storage of a skill, i.e., the motor memory trace. If a
      reflection of the trace, such modifications should persist after training is
      stopped for as long as the skill is retained. The objective here was to test the
      persistence of learning-related changes in the representation of the forelimb of
      the rat after learning a reaching task using repeated epidural stimulation
      mapping of primary motor cortex. It is shown that the forelimb representations
      enlarge after 8 days of training (n=8) but contract while performing arm
      movements without learning (n=7, p=0.006); hindlimb representations remain
      unchanged. Enlargement correlated with learning success (r=0.82; p=0.012).
      Subsequently, after 8 days without training, representation size reverted to
      baseline while the motor skill was retained. Somatotopy remained unaltered by a
      second training phase in which performance did not improve further (n=5). These
      findings suggest that successful acquisition but not storage of a motor skill
      depends on cortical map changes. The motor memory trace in rats may require
      changes in motor cortex organization other than those detected by stimulation
      mapping.

PMID- 18329290
TI  - Effective connectivity during haptic perception: a study using Granger causality
      analysis of functional magnetic resonance imaging data.
AB  - Although it is accepted that visual cortical areas are recruited during touch, it
      remains uncertain whether this depends on top-down inputs mediating visual
      imagery or engagement of modality-independent representations by bottom-up
      somatosensory inputs. Here we addressed this by examining effective connectivity
      in humans during haptic perception of shape and texture with the right hand.
      Multivariate Granger causality analysis of functional magnetic resonance imaging
      (fMRI) data was conducted on a network of regions that were shape- or texture
      selective. A novel network reduction procedure was employed to eliminate
      connections that did not contribute significantly to overall connectivity.
      Effective connectivity during haptic perception was found to involve a variety of
      interactions between areas generally regarded as somatosensory, multisensory,
      visual and motor, emphasizing flexible cooperation between different brain
      regions rather than rigid functional separation. The left postcentral sulcus
      (PCS), left precentral gyrus and right posterior insula were important sources of
      connections in the network. Bottom-up somatosensory inputs from the left PCS and
      right posterior insula fed into visual cortical areas, both the shape-selective
      right lateral occipital complex (LOC) and the texture-selective right medial
      occipital cortex (probable V2). In addition, top-down inputs from left postero
      supero-medial parietal cortex influenced the right LOC. Thus, there is strong
      evidence for the bottom-up somatosensory inputs predicted by models of visual
      cortical areas as multisensory processors and suggestive evidence for top-down
      parietal (but not prefrontal) inputs that could mediate visual imagery. This is
      consistent with modality-independent representations accessible through both
      bottom-up sensory inputs and top-down processes such as visual imagery.

PMID- 18329291
TI  - Calibrated fMRI in the medial temporal lobe during a memory-encoding task.
AB  - Prior measures of the blood oxygenation level-dependent (BOLD) and cerebral blood
      flow (CBF) responses to a memory-encoding task within the medial temporal lobe
      have suggested that the coupling between functional changes in CBF and changes in
      the cerebral metabolic rate of oxygen (CMRO(2)) may be tighter in the medial
      temporal lobe as compared to the primary sensory areas. In this study, we used a
      calibrated functional magnetic resonance imaging (fMRI) approach to directly
      estimate memory-encoding-related changes in CMRO(2) and to assess the coupling
      between CBF and CMRO(2) in the medial temporal lobe. The CBF-CMRO(2) coupling
      ratio was estimated using a linear fit to the flow and metabolism changes
      observed across subjects. In addition, we examined the effect of region-of
      interest (ROI) selection on the estimates. In response to the memory-encoding
      task, CMRO(2) increased by 23.1+/-8.8% to 25.3+/-5.7% (depending upon ROI), with
      an estimated CBF-CMRO(2) coupling ratio of 1.66+/-0.07 to 1.75+/-0.16. There was
      not a significant effect of ROI selection on either the CMRO(2) or coupling ratio
      estimates. The observed coupling ratios were significantly lower than the values
      (2 to 4.5) that have been reported in previous calibrated fMRI studies of the
      visual and motor cortices. In addition, the estimated coupling ratio was found to
      be less sensitive to the calibration procedure for functional responses in the
      medial temporal lobe as compared to the primary sensory areas.

PMID- 18329292
TI  - The impact of temporal regularization on estimates of the BOLD hemodynamic
      response function: a comparative analysis.
AB  - In fMRI data analysis it has been shown that for a wide range of situations the
      hemodynamic response function (HRF) can be reasonably characterized as the
      impulse response function of a linear and time invariant system. An accurate and
      robust extraction of the HRF is essential to infer quantitative information about
      the relative timing of the neuronal events in different brain regions. When no
      assumptions are made about the HRF shape, it is most commonly estimated using
      time windowed averaging or a least squares estimated general linear model based
      on either Fourier or delta basis functions. Recently, regularization methods have
      been employed to increase the estimation efficiency of the HRF; typically these
      methods produce more accurate HRF estimates than the least squares approach
      [Goutte, C., Nielsen, F.A., Hansen, L.K., 2000. Modeling the Haemodynamic
      Response in fMRI Using Smooth FIR Filters. IEEE Trans. Med. Imag. 19(12), 1188
      1201.]. Here, we use simulations to clarify the relative merit of temporal
      regularization based methods compared to the least squares methods with respect
      to the accuracy of estimating certain characteristics of the HRF such as time to
      peak (TTP), height (HR) and width (W) of the response. We implemented a Bayesian
      approach proposed by Marrelec et al. [Marrelec, G., Benali, H., Ciuciu, P.,
      Pelegrini-Issac, M., Poline, J.-B., 2003. Robust Estimation of the Hemodynamic
      Response Function in Event-Related BOLD fMRI Using Basic Physiological
      Information. Hum. Brain Mapp. 19, 1-17., Marrelec, G., Benali, H., Ciuciu, P.,
      Poline, J.B. Bayesian estimation of the hemodynamic of the hemodynamic response
      function in functional MRI. In: R. F, editor; 2001; Melville. p 229-247.] and its
      deterministic counterpart based on a combination of Tikhonov regularization
      [Tikhonov, A.N., Arsenin, V.Y., 1977. Solution of ill-posed problems. Washington
      DC: W.H. Winston.] and generalized cross-validation (GCV) [Wahba, G., 1990.
      Spline Models for Observational Data. Philadelphia: SIAM.] for selecting the
      regularization parameter. The performance of both methods is compared with least
      square estimates as a function of temporal resolution, color and strength of the
      noise, and the type of stimulus sequences used. In almost all situations, under
      the considered assumptions (e.g. linearity, time invariance and smooth HRF), the
      regularization-based techniques more accurately characterize the HRF compared to
      the least-squares method. Our results clarify the effects of temporal resolution,
      noise color, and experimental design on the accuracy of HRF estimation.

PMID- 18329293
TI  - Human secondary somatosensory cortex is involved in the processing of
      somatosensory rare stimuli: an fMRI study.
AB  - In the human somatosensory system, the contralateral primary somatosensory cortex
      (SI) is presumed to process and encode type and intensity of the sensory inputs,
      whereas the bilateral secondary somatosensory cortex (SII) is believed to perform
      higher order functions including sensorimotor integration, integration of
      information from the two body halves, attention, learning and memory. In this
      fMRI study we investigated the effect of attention on the activation of SI and
      SII, as induced by nonpainful and painful rare deviant electric stimuli during
      somatosensory oddball tasks. The working hypothesis is of stronger effects of
      attention on SII with respect to SI. Four runs were acquired according to an
      oddball scheme. Frequent nonpainful electrical stimuli were delivered to the
      ulnar nerve at motor threshold, whereas rare/deviant stimuli were delivered to
      median nerve in four conditions (one condition per run): nonpainful, painful,
      counting nonpainful, and counting painful. Results showed a statistically
      significant fMRI activation in bilateral SII but not in contralateral SI when the
      rare/deviant median nerve stimuli were delivered at nonpainful and painful levels
      as well as at the two levels of attention considered (i.e., associated with
      counting and non-counting tasks). Furthermore, fMRI activation in SII did not
      differ across the different levels of stimulus intensity (nonpainful, painful)
      and attention (non-counting, counting). These results corroborate the notion that
      SII is the target of independent pathways for the processing and integration of
      nonpainful and painful somatosensory stimuli salient for further high-order
      elaborations.

PMID- 18329294
TI  - Subscapularis dysfunction following anterior surgical approaches to the shoulder.
AB  - Subscapularis dysfunction following open surgical exposure of the glenohumeral
      joint has recently received attention. Clinical studies, in particular those that
      have investigated the results after open shoulder stabilization or shoulder
      replacement surgery, indicate that anterior approaches using different
      subscapularis tendon take-down or incision techniques may impair subscapularis
      recovery and can negatively influence the final clinical outcome. This review
      article will focus on the potential pathogenesis, diagnosis, and clinical impact
      of this more and more recognized condition and summarizes the currently available
      literature.

PMID- 18329295
TI  - Young patients with shoulder chondrolysis following arthroscopic shoulder surgery
      treated with total shoulder arthroplasty.
AB  - Chondrolysis following shoulder arthroscopy is a devastating complication, often
      seen in young patients. After nonoperative measures have been exhausted, there
      are few treatment options available that reliably improve pain and function. The
      purpose of this study is to examine the intra-operative findings, radiographic
      features, and clinical outcomes of a series of patients with chondrolysis
      following arthroscopic surgery managed with a total shoulder arthroplasty. A
      retrospective review was performed on 11 patients (average age 39) with shoulder
      chondrolysis following arthroscopy. Attention was focused on review of the index
      arthroscopy, radiographs, and functional outcome scores prior to total shoulder
      arthroplasty, as well as intra-operative cultures, histology, radiographs, and
      functional outcomes from most recent follow-up. All patients were treated with
      total shoulder arthroplasty at an average of 26 months after the index
      arthroscopy. Preoperative and postoperative radiographs were reviewed, and
      outcomes were compared using validated measurements. Statistically significant
      improvements in shoulder abduction (89 degrees -123 degrees , P = .027), external
      rotation (26 degrees -48 degrees , P = .037), total ASES scores (30-77.5, P =
      .0039), and SST scores (3-8, P = .0078) were noted. Ten patients subjectively
      rated their outcomes as good or excellent, with 1 as satisfactory. Chondrolysis
      after shoulder arthroscopy has a rapid clinical progression and is likely
      multifactorial in etiology. Early results of total shoulder arthroplasty show an
      opportunity for improvements in pain and function; however, progressive glenoid
      radiolucencies may develop in these patients.

PMID- 18329296
TI  - The influence of C3435T polymorphism of ABCB1 gene on penetration of
      phenobarbital across the blood-brain barrier in patients with generalized
      epilepsy.
AB  - BACKGROUND: Epilepsy is refractory to medical treatment in about one-third of the
      patients. The exact pathological mechanism of epilepsy pharmacoresistance is
      still unclear, but a decreased antiepileptic drug (AED) uptake into the brain is
      suspected to play a role. P-glycoprotein (Pgp), a transmembrane transporter
      encoded by ABCB1 gene and located at the endothelial cells of the blood-brain
      barrier (BBB), has been associated with epilepsy pharmacoresistance. OBJECTIVE:
      To analyze the effect of two ABCB1 gene polymorphisms, C3435T and G2677T/A, on
      phenobarbital (PB) concentrations in the cerebrospinal fluid (CSF) and serum (S)
      and to assess the relationship of ABCB1 polymorphisms to phenobarbital
      penetration across BBB in vivo and seizure frequency. METHODS: CSF PB and S PB
      concentrations were measured in 60 patients with idiopathic primary generalized
      epilepsy receiving phenobarbital monotherapy. CSF/S PB concentration ratio was
      calculated as an index of phenobarbital penetration across BBB. The patients were
      genotyped for the ABCB1 gene C3435T and G2677T/A polymorphisms. Seizure frequency
      was recorded during the 6-month phenobarbital monotherapy. RESULTS: Patients with
      different C3435T polymorphism had significantly different CSF PB concentrations
      and CSF/S PB concentration ratio. In comparison with CT heterozygotes and TT
      homozygotes, CC homozygotes had a significantly lower CSF PB concentration
      (p=0.006) and CSF/PB concentration ratio (p<0.001). G2677T/A polymorphism showed
      no such effect (p=0.466). CC genotype and low CSF/S PB concentration ratio
      correlated with increased seizure frequency. CONCLUSIONS: C3435T polymorphism of
      ABCB1 gene was demonstrated in vivo to significantly influence the CSF/S PB
      concentration ratio and seizure frequency.

PMID- 18329297
TI  - Transient lesion in the splenium related to antiepileptic drug: case report and
      new pathophysiological insights.
AB  - Transient focal lesions in the splenium of the corpus callosum (SCC) have been
      associated with antiepileptic drug (AED) treatment. However, the aetiology is
      widely unknown. We describe a transient SCC lesion in an epilepsy patient after
      abrupt AED reduction. Whole head high-field diffusion tensor imaging (DTI)
      including fully automated quantitative fractional anisotropy (FA) analysis was
      used to get insight into the pathophysiology of transient SCC lesions. Our
      results demonstrate that a reversible loss of directional fibre organisation in
      the splenium, likely due to intramyelinic oedema, is the morphological correlate
      of transient SCC lesions. We conclude that DTI provides a highly sensitive and
      quantitative tool to detect subtle and transient loss of fibre integrity
      associated with AED treatment.

PMID- 18329298
TI  - False recognition of emotional stimuli is lateralised in the brain: An fMRI
      study.
AB  - We have investigated whether the left (LH) and right (RH) hemisphere play a
      different role in eliciting false recognition (FR) and whether their involvement
      in this memory illusion depends on the emotional content of stimuli. Negative and
      neutral pictures (taken from IAPS) were presented in the divided-visual field
      paradigm. Subjects task was to indicate whether the pictures had already been
      presented or not during the preceding study phase. FR rate was much higher for
      the RH than the LH presentations. In line, FR resulted in activations mainly in
      the right prefrontal cortex (PFC) for either RH or LH presentations. Emotional
      content of stimuli facilitated the formation of false memories and strengthened
      the involvement of the right PFC in FR induction.

PMID- 18329300
TI  - Development and evaluation of a reverse dot blot assay for the simultaneous
      detection of six common Chinese G6PD mutations and one polymorphism.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited
      disorder worldwide including southern China. We developed and validated a reverse
      dot blot (RDB) assay for the rapid and simultaneous genotyping of six mutations
      (c.95A>G, c.871G>A, c.1004C>T, c.1024C>T, c.1376G>T and c.1388G>A), that were
      common mutations in the Chinese G6PD deficiency population, and one polymorphism
      (c.1311C>T). Reliable genotyping of wild-type and mutant genomic DNA samples was
      achieved by means of a test strip onto which allele-specific oligonucleotide
      probe lines are fixed in parallel. This method involves a multiplex PCR
      amplification of three fragments in the G6PD target sequence and a manual
      hybridization/detection protocol. The entire procedure starting from blood
      sampling to the identification of mutations requires less than 6 h. The
      diagnostic reliability of this reverse dot blot assay was evaluated on 207 pre
      typed samples by using direct DNA sequence analysis in a blind study. The reverse
      dot blot typing was in complete concordance with the reference method. The
      reverse dot blot assay was proved to be a simple, rapid, highly accurate, and
      cost-effective method to identify common G6PD mutations in Chinese population.

PMID- 18329299
TI  - Reduced DIDS-sensitive chloride conductance in Ae1-/- mouse erythrocytes.
AB  - The resting membrane potential of the human erythrocyte is largely determined by
      a constitutive Cl(-) conductance approximately 100-fold greater than the resting
      cation conductance. The 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS)
      sensitive electroneutral Cl(-) transport mediated by the human erythroid Cl(
      )/HCO(3)(-) exchanger, AE1 (SLC4A1, band 3) is >10,000-fold greater than can be
      accounted for by the Cl(-) conductance of the red cell. The molecular identities
      of conductive anion pathways across the red cell membrane remain poorly defined.
      We have examined red cell Cl(-) conductance in the Ae1(-/-) mouse as a genetic
      test of the hypothesis that Ae1 mediates DIDS-sensitive Cl(-) conductance in
      mouse red cells. We report here that wildtype mouse red cell membrane potential
      resembles that of human red cells in the predominance of its Cl(-) conductance.
      We show with four technical approaches that the DIDS-sensitive component of
      erythroid Cl(-) conductance is reduced or absent from Ae1(-/-) red cells. These
      results are consistent with the hypothesis that the Ae1 anion exchanger
      polypeptide can operate infrequently in a conductive mode. However, the fragile
      red cell membrane of the Ae1(-/-) mouse red cell exhibits reduced abundance or
      loss of multiple polypeptides. Thus, loss of one or more distinct, DIDS-sensitive
      anion channel polypeptide(s) from the Ae1(-/-) red cell membrane cannot be ruled
      out as an explanation for the reduced DIDS-sensitive anion conductance.

PMID- 18329301
TI  - Milk fever in dairy cows: a review of pathophysiology and control principles.
AB  - The periparturient or transition period of 4 weeks before and 4 weeks after
      calving is characterised by a greatly increased risk of disease. Hypocalcaemia
      around calving is a risk factor for many of these diseases and is an indirect
      risk factor for increased culling. The incidence of clinical hypocalcaemia (milk
      fever) in the field generally ranges from 0-10%, but may exceed 25% of cows
      calving. In research trials conducted on milk fever the incidence has approached
      80% of cows calving. Homeostasis of calcium (Ca) is regulated by calcitonin,
      parathyroid hormone and 1,25(OH)(2) vitamin D(3). Age increases the risk of milk
      fever by approximately 9% per lactation. Control of milk fever has revolved
      around stimulation of homeostatic mechanisms through feeding a pre-calving diet
      low in Ca. More recently, the role of the dietary cation anion difference (DCAD)
      in the prevention of Ca disorders has been examined, both by field research and
      meta-analysis. The most appropriate form of the DCAD equation has been
      contentious, but recent meta-analyses have shown that the equation (Na(+)+K(+))
      (Cl(-)+S(2-)) is most effective for predicting milk fever risk. Decreased risk of
      milk fever is linear with DCAD, whereas the effect of DCAD on urinary pH is
      curvilinear. A pivotal role of providing dietary magnesium (Mg) before calving
      has been confirmed by meta-analysis, and a quadratic effect of Ca on milk fever
      risk was found with a peak occurring with dietary levels of 1.1-1.3% of dry
      matter. Risks of milk fever increase with increased dietary phosphorus (P) fed
      pre-calving and with increasing days of exposure to a pre-calving diet. Meta
      analysis has revealed that the important roles of dietary Ca, Mg and P, as well
      as the duration of exposure to the pre-calving diet in milk fever control
      strategies are independent of DCAD. Studies on the effect of exposure to well
      designed pre-calving diets have shown that substantial improvements in
      production, reproduction and animal health can be made but further examination of
      the influence of the period of exposure to different diets is warranted.

PMID- 18329303
TI  - Is there a role for organic trace element supplements in transition cow health?
AB  - Optimal transition cow health is the key to success of the subsequent lactation,
      and increasing attention has been focused on management and nutritional practices
      that support it. Physiological stress during the transition period alters the
      efficiency of the immune system, making the lactating dairy cow more susceptible
      to infectious diseases, such as mastitis and metritis, with subsequent impairment
      of reproductive performance. Trace elements have a specific role in free radical
      control at the cellular level and influence the anti-oxidant/free radical
      balance. Dietary trace elements must be available for absorption throughout the
      whole of the digestive process until they reach the final site of absorption in
      the small intestine. Negative interactions between minerals can occur and, as the
      intestinal environment lowers the absorption of ionic minerals, chelation
      technology has been developed to increase mineral bioavailability. Organic trace
      elements have been used in dairy cow experiments, resulting in significant
      improvements in udder health, lameness and reproductive performance.

PMID- 18329302
TI  - Uterine diseases in cattle after parturition.
AB  - Bacterial contamination of the uterine lumen is common in cattle after
      parturition, often leading to infection and uterine disease. Clinical disease can
      be diagnosed and scored by examination of the vaginal mucus, which reflects the
      presence of pathogenic bacteria such as Escherichia coli and Arcanobacterium
      pyogenes. Viruses may also cause uterine disease and bovine herpesvirus 4 (BoHV
      4) is tropic for endometrial cells, causing a rapid cytopathic effect. The
      elimination of pathogens by the innate immune system is dependent on pattern
      recognition receptors binding pathogen-associated molecules. Uterine epithelial
      and stromal cells express receptors such as Toll-like Receptor 4 that binds E.
      coli lipopolysaccharide. The infertility associated with uterine disease is
      caused by damage to the endometrium and disruption of ovarian cyclic activity.
      Bacteria modulate endometrial prostaglandin secretion, and perturb ovarian
      follicle growth and function. Understanding the molecular basis of uterine
      disease will lead to novel approaches to treating infertility.

PMID- 18329304
TI  - Compensation of gradient-induced magnetic field perturbations.
AB  - Pulsed magnetic field gradients are essential for MR imaging and localized
      spectroscopy applications. However, besides the desired linear field gradients,
      pulsed currents in a strong external magnetic field also generate unwanted
      effects like eddy currents, gradient coil vibrations and acoustic noise. While
      the temporal magnetic field perturbations associated with eddy currents lead to
      spectral line shape distortions and signal loss, the vibration-related
      modulations lead to anti-symmetrical sidebands of any large signal (i.e. water),
      thereby obliterating the signals from low-concentration metabolites. Here the
      measurement, characterization and compensation of vibration-related magnetic
      field perturbations is presented. Following a quantitative evaluation of the
      various temporal components of the main magnetic field, a digital B0 magnetic
      field waveform is generated which reduces all temporal variations of the main
      magnetic field to within the spectral noise level.

PMID- 18329305
TI  - Model of the extracellular domain of the human alpha7 nAChR based on the crystal
      structure of the mouse alpha1 nAChR extracellular domain.
AB  - Neuronal nicotinic acetylcholine receptors (nAChRs) are important therapeutic
      targets for various diseases, including Alzheimer's disease, Parkinson's disease,
      and schizophrenia, as well as for cessation of smoking. Based on the recently
      determined crystal structure of the extracellular domain (ECD) of the mouse nAChR
      alpha1 subunit complexed with alpha-bungarotoxin at 1.94A resolution, we have
      constructed three-dimensional models of the ECD of the monomer, homodimer, and
      homopentamer of the human alpha7 nAChR and investigated in detail the interface
      between the two alpha7 subunits. The docking of the agonist in the ligand-binding
      pocket of the human alpha7 dimer was also performed and found consistent with
      results from labeling and mutagenesis experiments. Since the nAChR ligand-binding
      site is a useful target for mutagenesis studies and the rational design of drugs
      against diseases, these models provide useful information for future work.

PMID- 18329306
TI  - Volumetric response of vertebrate hepatocytes challenged by osmotic gradients: a
      theoretical approach.
AB  - In this study we use a theoretical approach to study the volumetric response of
      goldfish hepatocytes challenged by osmotic gradients and compared it with that of
      hepatocytes from another teleost (the trout) and a mammal (the rat). Particular
      focus was given to the multiple non-linear interactions of transport systems
      enabling hypotonically challenged cells to trigger a compensatory response known
      as volume regulatory decrease or RVD. For this purpose we employed a mathematical
      model which describes the rates of change of the intracellular concentrations of
      main diffusible ions, of the cell volume, and of the membrane potential. The
      model was fitted to experimental data on the kinetics of volume change of
      hepatocytes challenged by anisotonic media. In trout and rat hepatocytes,
      experimental results had shown that hypotonic cell swelling was followed by RVD,
      whereas goldfish cells swelled with no concomitant RVD (M.V. Espelt et al., 2003,
      J. Exp. Biol. 206, 513-522). A comparison between data predicted by the model and
      that obtained experimentally suggests that in trout and rat hepatocytes
      hypotonicity activates a sensor element and this, in turn, activates an otherwise
      silent efflux of KCl - whose kinetics could be successfully predicted - thereby
      leading to volume down-regulation. In contrast, with regard to the absence of RVD
      in goldfish hepatocytes the model proposed suggests that either a sensor element
      triggering RVD is absent or that the effector mechanism (the loss of KCl) remains
      inactive under the conditions employed. In line with this, we recently found that
      extracellular nucleotides may be required to induce RVD in these cells,
      indicating that our model could indeed lead to useful predictions.

PMID- 18329307
TI  - Functional maturation of growth hormone cells in the anterior pituitary gland of
      the fetus.
AB  - Recent studies have disclosed the molecular mechanisms responsible for the
      phenotype determination of the anterior pituitary cell types. However, as far as
      growth hormone (GH) cells are concerned, particular extra-cellular cues are
      required for the initiation of GH and GH-releasing hormone (GHRH)-receptor gene
      production in addition to the expression of the cell type specific transcription
      factor, pit-1. The glucocorticoids play a principal role in the functional
      maturation of nascent GH cells in the fetal pituitary glands in rodents, inducing
      GH and GHRH-receptor gene expression, and establish the GH secretory system
      regulated by the brain in late gestation. Research supporting this role for
      glucocorticoid in the development of GH cells is discussed.

PMID- 18329308
TI  - Reference values of IGF-I in children from birth to 5 years of age, in Burkina
      Faso, using blood samples on filter paper.
AB  - OBJECTIVES: The aims of this study were to validate the use of filter paper to
      measure insulin-like growth factor-I (IGF-I) and to establish normal levels of
      IGF-I in children appearing healthy, from birth to 5 years of age in an African
      population. METHODS: We determined IGF-I from blood collected on filter paper. We
      validated this method by comparing the IGF-I values from dried blood spots on
      filter paper (kept at 4 degrees C and ambient temperature) and from serum among
      13 children under 5. IGF-I were measured by the classical IGF-I RIA, after
      separation of the IGF-I from its binding proteins, using Sep-Pak chromatography.
      To establish normal levels of IGF-I, we conducted a cross-sectional study and
      collected blood samples with filter paper among 360 children in Ouagadougou
      (Burkina Faso). RESULTS: IGF-I determined from dried blood spots on filter paper
      were in good agreement with IGF-I levels obtained from blood serum, whether the
      filter papers were kept at 4 degrees C or at ambient temperature. The results of
      IGF-I-levels in apparently healthy children showed that geometric mean IGF-I
      ranged from 27 microg/l in boys younger than five months to 31 microg/l in 5-year
      old boys. In girls, mean IGF-I ranged from 29 microg/l for girls younger than
      five months to 45 microg/l at the age of 5. From birth to 24 months, IGF-I
      decreased by 0.32+/-0.08 microg/l/month in boys and by 0.27+/-0.06 microg/l/month
      in girls and these decreases were not significantly different (p=0.95). After the
      age of 24 months, there was an increase in IGF-I of 4.9+/-1.3 microg/l/year in
      boys and of 8.4+/-0.8 microg/l/year in girls. This increase was indeed
      significantly different (p<0.001). CONCLUSIONS: Reference values of IGF-I for
      African boys and girls were determined. They will be used for endocrine
      evaluations and nutritional monitoring.

PMID- 18329309
TI  - Plasma 15-F2t isoprostane concentrations are increased during acute fructose
      loading in type 2 diabetes.
AB  - OBJECTIVE: Fructose consumption is increasing worldwide and is likely to play a
      role in metabolic disorders. Dietary fructose is often recommended for diabetic
      patients, as this form of carbohydrate leads to a lower postprandial rise in
      plasma glucose and insulin. However, fructose contributes to the generation of
      free radicals. The aim of this work was to investigate the acute effects of a
      fructose load in patients with type 2 diabetes mellitus (T2DM), compared with
      healthy controls, on several metabolic oxidative biomarkers, particularly plasma
      15-F2t isoprostanes (15-F2t isoPs). RESEARCH DESIGN AND METHODS: Six T2DM
      patients and six healthy subjects were recruited. All patients underwent a single
      fructose tolerance test (75 g of anhydrous fructose). Plasma 15-F2t isoPs
      concentrations, plasma total antioxidant capacity (TAS) and thiobarbituric acid
      reactive substances (TBARS) were measured at baseline, and at 60, 120, 180 and
      240 min after fructose absorption. RESULTS: Baseline plasma 15-F2t isoPs
      concentrations were significantly increased in T2DM patients compared with
      controls (310+/-47 versus 237+/-20 pg/mL, respectively; P<0.01) and rose
      significantly (P<0.01) to 414+/-45 pg/mL in diabetic patients. No change in TAS
      or TBARS was observed in either group. CONCLUSION: Plasma 15-F2t isoPs are
      increased during acute fructose loading in T2DM. Knowing the potentially
      deleterious effect of plasma 15-F2t isoPs-in particular, vascular lesions-and in
      light of our results, it is necessary to reconsider fructose consumption in T2DM
      patients, as we can now show, for the first time, a possible association between
      acute fructose loading and deleterious effects in such patients.

PMID- 18329310
TI  - Inclusion of C-reactive protein in the identification of metabolically healthy
      but obese (MHO) individuals.

PMID- 18329311
TI  - Uneventful pregnancy in a patient with ketosis-prone type 2 diabetes mellitus.

PMID- 18329312
TI  - Distribution of HLA-B*27 subtypes in Tunisians and their association with
      ankylosing spondylitis.
AB  - OBJECTIVE: The human leukocyte antigen HLA-B27 is a class I antigen of the major
      histocompatibility complex strongly associated with ankylosing spondylitis (AS)
      and other related spondyloarthropathies (SpAs). The mechanism of this association
      remains unknown. HLA-B27 is a serologic specificity that represents a family of
      at least 25 different HLA-B27 alleles (2701-2725). These alleles are closely
      related by nucleotide sequence homology, but differ in ethnic distribution. The
      purpose of the present study is to investigate the distribution of HLA-B27
      alleles in healthy controls and in patients with ankylosing spondylitis (AS).
      METHODS: We selected 160 HLA-B27-positive individuals (39 controls and 121
      patients with ankylosing spondylitis). Typing of HLA-B27, and Cw alleles were
      performed by polymerase chain reaction amplification with sequence specific
      primers (PCR-SSP), and by serological typing (microlymphocytotoxicity). RESULTS:
      Seven B27 subtypes were identified: B*2702, 03, 04, 05, 07, 09 and B*2714. The
      distribution of these alleles in the population of patients was B*2702 (47.1%)
      and B*2705 (47.1%). These subtypes were also detected in 16 (41%) and 16 (41%),
      respectively of the 39 control subjects. HLA-B*2707 was detected in 4 (3.31%)
      patients and in 3 (7.6%) controls. B*2704, 09 and B*2714 were relatively rare and
      were detected in one subject each. No significant differences were noticed in the
      frequencies and distribution of HLA-B27 alleles between patients and controls.
      CONCLUSIONS: Our results show a restricted number of HLA B27 subtypes associated
      with AS. B*2702 and B*2705 were equally common in patients and controls. The most
      prominent B27/Cw haplotypes in the patient groups and controls were
      B*2702/Cw02022 and B*2705/Cw02022.

PMID- 18329313
TI  - [Should tocolytics be used in premature rupture of membranes (PROM)? The pros].

PMID- 18329314
TI  - Centrins in retinal photoreceptor cells: regulators in the connecting cilium.
AB  - Changes in the intracellular Ca2+ concentration regulate the visual signal
      transduction cascade directly or more often indirectly through Ca2+-binding
      proteins. Here we focus on centrins, which are members of a highly conserved
      subgroup of the EF-hand superfamily of Ca2+-binding proteins in photoreceptor
      cells of the vertebrate retina. Centrins are commonly associated with centrosome
      related structures. In mammalian retinal photoreceptor cells, four centrin
      isoforms are expressed as prominent components in the connecting cilium linking
      the light-sensitive outer segment compartment with the metabolically active inner
      segment compartment. Our data indicate that Ca2+-activated centrin isoforms
      assemble into protein complexes with the visual heterotrimeric G-protein
      transducin. This interaction of centrins with transducin is mediated by binding
      to the betagamma-dimer of the heterotrimeric G-protein. More recent findings show
      that these interactions of centrins with transducin are reciprocally regulated
      via site-specific phosphorylations mediated by the protein kinase CK2. The
      assembly of centrin/G-protein complexes is a novel aspect of translocation
      regulation of signalling proteins in sensory cells, and represents a potential
      link between molecular trafficking and signal transduction in general.

PMID- 18329315
TI  - Potential applications of nanotechnologies to Parkinson's disease therapy.
AB  - Nanotechnology will play a key role in developing new diagnostic and therapeutic
      tools. Nanotechnologies use engineered materials with the smallest functional
      organization on the nanometre scale in at least one dimension. Some aspects of
      the material can be manipulated resulting in new functional properties.
      Nanotechnology could provide devices to limit and reverse neuropathological
      disease states, to support and promote functional regeneration of damaged
      neurons, to provide neuroprotection and to facilitate the delivery of drugs and
      small molecules across the blood-brain barrier. All of them are relevant to
      improve current therapy of Parkinson's disease (PD).

PMID- 18329316
TI  - Identification of the novel D297fsX318 PINK1 mutation and phenotype variation in
      a family with early-onset Parkinson's disease.
AB  - Herein we first describe a novel homozygous single nucleotide deletion in PINK1
      exon 4 (889delG) which results in a loss of kinase domain on the PINK1 protein
      (D297fsX318). This mutation was identified in two brothers with early-onset
      Parkinson disease (EOPD) from a Sicilian consanguineous family. Of note, while
      one of the two patients developed mental deterioration and psychiatric problems,
      the other showed no cognitive decline. The present study supports the view that
      PINK1 is a pathogenic gene in some Italian families with EOPD and contributes to
      define the PINK1-associated phenotype.

PMID- 18329317
TI  - Validation of the sleep related items of the Non-motor Symptoms Questionnaire for
      Parkinson's disease (NMSQuest).
AB  - BACKGROUND: The Non-motor Symptoms Questionnaire (NMSQuest) is a recently
      developed questionnaire for the evaluation of non-motor symptoms in Parkinson's
      disease (PD) patients, which includes sleep disorders evaluation. The clinical
      validity of the questionnaire has not been explored. OBJECTIVE: To assess the
      performance of the sleep/fatigue domain of the NMSQuest against other sleep
      measures. METHODS: Seventy PD patients were instructed to wear an actigraph and
      to fill in a sleep log over seven consecutive days in addition to the Parkinson's
      Disease Sleep Scale (PDSS) and the NMSQuest. RESULTS: PD patients who reported
      daytime sleepiness on NMSQuest obtained a significantly worse score on the PDSS
      sleepiness domain than PD patients who did not (12.0+/-4.7 vs. 14.7+/-3.4,
      p<0.009). Patients reporting difficulty getting to sleep or staying asleep at
      night, showed lower scores on PDSS sleep quality domain than those without
      difficulties (15.8+/-5.4 vs. 22.3+/-4.6, p<0.001). The presence of vivid dreams,
      acting out dreams and restlessness on NMSQuest correlated with PDSS and sleep log
      scores. Increased nocturnal activity was noted in subjects reporting acting out
      dreams. Furthermore, the number of positive answers to the sleep-fatigue
      questions of the NMSQuest correlated significantly with PDSS total score, sleep
      log total score and nocturnal activity measured by actigraphy. CONCLUSION:
      NMSQuest sleep-fatigue domain identified appropriately sleep disturbances
      indicating its usefulness as a screening tool for sleep disorders in PD patients.

PMID- 18329318
TI  - The spectrum of disorders presenting as adult-onset focal lower extremity
      dystonia.
AB  - BACKGROUND: Uncommonly, adult-onset dystonia is confined to one lower extremity.
      We sought to characterize the clinical spectrum associated with the presenting
      phenotype of lower limb dystonia including foot torsion. METHODS: Retrospective
      computer search of the Mayo Clinic Medical Records Linkage System (1996-2006).
      Inclusion criteria were (1) a principal, initial diagnosis of monomelic lower
      extremity dystonia with foot torsion; (2) no neurologic findings outside of the
      affected limb; (3) age-onset>18 years. Prospective data were sought from apparent
      idiopathic cases. RESULTS: We identified 36 patients (31 females) presenting with
      monomelic lower limb dystonia including foot torsion. Onset was usually subacute
      or insidious (32 patients); mean symptom duration was 28.8 months (range, 1-96),
      age-onset 47.5 years (range, 21-77). After a mean follow-up of 3.1 years, causes
      were identified in over half, including 5 with parkinsonism. Other treatable
      etiologies included psychogenic dystonia (3 patients) and stiff-limb syndrome (2
      patients). Post-traumatic dystonia was diagnosed in 10 patients and consistently
      manifested as fixed, painful foot torsion, in contrast to the action-induced
      dystonia in 5 parkinsonism cases, and 10 of 14 patients with primary lower limb
      dystonia. Imaging identified the cause in only 1 patient (ischemic stroke) and
      was negative in the single patient with pyramidal signs. CONCLUSIONS: Adults
      presenting with monomelic lower limb dystonia with foot torsion often have an
      identifiable cause, sometimes treatable, including Parkinson's disease (diagnosed
      with levodopa trial) or immune-mediated stiff-limb syndrome. Post-traumatic
      dystonia was the single most frequent cause and proved difficult to treat. Unlike
      certain other series of such patients, psychogenic dystonia was an uncommon
      clinical diagnosis.

PMID- 18329319
TI  - Charting plant interactomes: possibilities and challenges.
AB  - Protein-protein interactions are essential for nearly all cellular processes.
      Therefore, an important goal of post-genomic research for defining gene function
      and understanding the function of macromolecular complexes involves creating
      'interactome' maps from empirical or inferred datasets. Systematic efforts to
      conduct high-throughput surveys of protein-protein interactions in plants are
      needed to chart the complex and dynamic interaction networks that occur
      throughout plant development. However, no single approach can build a complete
      map of the interactome. Here, we review the utility and potential of various
      experimental approaches for creating large-scale protein-protein interaction maps
      in plants. Bioinformatics approaches for curating and assessing the confidence of
      these datasets through inter-species comparisons will be crucial in achieving a
      complete understanding of protein interaction networks in plants.

PMID- 18329320
TI  - Cellulose-binding domains: cellulose associated-defensive sensing partners?
AB  - The cellulose-binding domains (CBDs) in the Phytophthora cellulose-binding
      elicitor lectin (CBEL) are potent elicitors of plant defence responses. Induction
      of defence has also been reported in various cellulose-deficient mutants of
      Arabidopsis thaliana. Based on these observations, we propose a model linking
      cellulose alteration to defence induction. This integrates the fast increase in
      cytosolic calcium recorded in response to CBEL, mechano-stimulated calcium uptake
      mechanisms, and proteins that interact functionally with the cellulose synthase
      complex. In this context, CBDs emerge as new tools to decipher the signalling
      cascades that result from cell wall-cellulose perturbations.

PMID- 18329321
TI  - Plant systems biology comes of age.
AB  - 'Omics' research approaches have produced copious data for living systems, which
      have necessitated the development of systems biology to integrate
      multidimensional biological information into networks and models. Applications of
      systems biology to plant science have been rapid, and have increased our
      knowledge about circadian rhythms, multigenic traits, stress responses and plant
      defenses, and have advanced the virtual plant project.

PMID- 18329322
TI  - Theory of mind, language and the temporoparietal junction mystery.
AB  - Brain imaging of adults during false-belief story tasks consistently shows
      activation of the temporoparietal junction in English-speaking Americans and
      German-speaking Europeans. Kobayashi et al. find this observation in adult
      English speakers but not in English-speaking children or in English-Japanese
      bilingual persons. This finding suggests a cultural or linguistic influence on
      location of brain function and argues against maturation of innately specified
      neural substrates. It is reminiscent of effects of linguistic development,
      bilingualism and cultural differences on theory of mind development.

PMID- 18329323
TI  - Attention regulation and monitoring in meditation.
AB  - Meditation can be conceptualized as a family of complex emotional and attentional
      regulatory training regimes developed for various ends, including the cultivation
      of well-being and emotional balance. Among these various practices, there are two
      styles that are commonly studied. One style, focused attention meditation,
      entails the voluntary focusing of attention on a chosen object. The other style,
      open monitoring meditation, involves nonreactive monitoring of the content of
      experience from moment to moment. The potential regulatory functions of these
      practices on attention and emotion processes could have a long-term impact on the
      brain and behavior.

PMID- 18329324
TI  - Intraoral adenoid cystic carcinoma: prognostic factors and outcome.
AB  - Intraoral (oral cavity and oropharynx) adenoid cystic carcinomas are uncommon
      cancers characterized by slow evolution, protracted clinical course, multiple
      and/or delayed recurrences, and late distant metastases. The molecular biology
      behind this enigmatic disease remains poorly characterized. To analyze and
      correlate prognostic factors with outcome in intraoral adenoid cystic carcinoma.
      Medical records of 76 patients with intraoral adenoid cystic carcinoma treated
      with definitive loco-regional therapy at the institute between 1992 and 2004 were
      retrospectively reviewed and analyzed.Majority (85.5%) of the patients had
      advanced stage disease. Seventy-four patients underwent surgery, of which 51
      (68.9%) received adjuvant radiotherapy. The median dose of radiation was 56 Gy
      (range 44-66 Gy). Two patients with medical co-morbidities received radical
      radiotherapy. Perineural invasion, margin positivity and nodal positivity were
      present in 24 (32.4%); 27 (36.4%); and 15 (19.7%) patients, respectively. Ten
      (13.1%) patients developed local recurrence and 6 (7.8%) distant metastases. With
      a median follow-up of 20 months (range 1-137 months), the 5-year Kaplan-Meier
      estimates of local control and disease-free survival were 57.9% and 47.1%,
      respectively. On uni-variate analysis, perineural invasion (p=0.003),
      oropharyngeal primary (p=0.033), and advanced T-stage (p=0.047) were associated
      with increased local recurrences. Perineural invasion (p=0.05) and primary site
      (p=0.042) also predicted disease-free survival. On multivariate analysis, both
      perineural invasion and primary site retained significance for local control
      (p=0.007, p=0.011) and disease-free survival (p=0.018, p=0.014), respectively.
      Intraoral adenoid cystic carcinoma is an uncommon disease with an enigmatic
      clinical course. Perineural invasion, site of primary, and T-stage significantly
      impact upon local control and disease-free survival. The role of adjuvant
      radiotherapy remains controversial. Larger prospective studies with mature follow
      up are needed to define the optimal treatment of intraoral adenoid cystic
      carcinoma.

PMID- 18329325
TI  - Risk factors for oral mucositis in children undergoing chemotherapy: a matched
      case-control study.
AB  - Oral mucositis (OM) is the most frequent and severe complication of chemotherapy
      for children with cancer, yet little is known about its risk factors. The aim of
      this study was to determine the risk factors associated with chemotherapy-induced
      OM in children. A matched case-control design was used. The matching criteria
      were age, type of cancer and chemotherapy regimen. Patient-and treatment-related
      data were collected via chart review. Conditional logistic regression analyses
      were performed to estimate odds ratios (OR) and adjusted odds ratios (AOR) for
      the development of OM. Fifty-one cases and 51 controls were identified. The
      mean+/-SD age of the children was 7.6+/-5.2 years, with 65 (63.73%) boys. Eighty
      two percent of the children had been diagnosed with haematological malignancies
      (n=84). The most common chemotherapy regimen was a combination of plant alkaloids
      and antitumor antibiotics (n=42, 41.18%). In the multivariable model, lower body
      weight (AOR=0.91; 95% CI=0.84-0.98; p=0.013), lower value of log nadir neutrophil
      count (AOR=0.33; 95% CI=0.16-0.68; p=0.0025), and higher value of peak creatinine
      (AOR=1.06; 95% CI=1.01-1.12; p=0.025) were significantly associated with a
      greater risk of OM. Our findings suggest that children who are neutropenic, those
      with serum creatinine elevation, and those with a low body weight prior to
      chemotherapy are at greater risk of developing OM.

PMID- 18329326
TI  - Presence of HPV DNA in convalescent salivary rinses is an adverse prognostic
      marker in head and neck squamous cell carcinoma.
AB  - Human papillomavirus (HPV) 16 is present in up to 60% of patients with head and
      neck squamous cell carcinoma (HNSCC) and confers a favorable prognosis in terms
      of recurrence and mortality. Previous reports demonstrated that HPV-16 DNA can be
      detected in the initial salivary rinses from these patients. In this study, we
      assessed the feasibility of post-treatment HPV DNA shed from the oral mucosa as a
      prognostic marker for persistent/recurrent head and neck cancer. Fresh tumor
      samples and pre- and post-treatment salivary rinses were collected from 59
      patients with HNSCC. HPV-16 E6 and E7 DNA copy number in these samples were
      quantified by real time PCR. Twenty of 59 patients (33.9%) were HPV-16 positive
      in their tumors before treatment. Four of 20 HPV tumor positive patients
      ultimately developed recurrence, and two of these four patients were HPV-16
      positive in surveillance salivary rinses (sensitivity=50%). Of the 39 (66.1%) HPV
      16 negative patients on initial clinical presentation and the 16 HPV-16 positive
      patients who did not recur, none were HPV-16 positive in salivary rinses after
      treatment (specificity=100%). HPV-16 presence in follow-up salivary rinses
      preceded clinical detection of disease recurrence by an average of 3.5 months.
      Patients with presence of HPV-16 DNA in surveillance salivary rinses are at
      significant risk for recurrence. Quantitative measurement of salivary HPV-16 DNA
      has promise for surveillance and early detection of recurrence.

PMID- 18329327
TI  - Comment on "An outline of the history of head and neck oncology" [Folz et al.
      Oral Oncol 2008;44(1):2-9].

PMID- 18329328
TI  - Expression of cell cycle associated proteins influences radiocurability of T2N0
      squamous cell carcinoma of the larynx.
AB  - Cell cycle modulators are important in carcinogenesis and may be of prognostic
      and therapeutic relevance. This study has examined the influence of the
      proliferation index (Ki-67) and immunocytochemical expression of epidermal growth
      factor receptor (EGFR), cyclin D1, and retinoblastoma protein on recurrence rates
      at the primary site in 50 patients with T2N0 laryngeal carcinomas treated with
      radical irradiation. Pre-treatment biopsies were retrieved and sections scored
      for the four immunocytochemical markers. Statistical analysis for association,
      interaction and survival was performed. Five cases showed loss of expression of
      Rb protein. The median Ki-67 index was 50%, the median cyclin D1 index 21% and
      the median EGFR index 47% of cells. EGFR and cyclin D1 expression were positively
      correlated and, whilst local recurrence tended to occur with a Ki-67 labelling
      index of <50%, this was not statistically significant. When interactions were
      examined using Multiple Logistic Regression it was found that there was a direct
      relationship between EGFR and cyclin D1 expression. If the EGFR index was >20%
      and the cyclin D1 index >10%, then the odds ratio in favour of a primary site
      recurrence was very high (5.32 +/-0.41). This study demonstrates that the
      relationship between EGFR index and cyclin D1 index has a very strong association
      with primary site recurrence for T2 N0 laryngeal carcinomas treated by
      irradiation.

PMID- 18329329
TI  - Genetic diversity in natural populations: a fundamental component of plant
      microbe interactions.
AB  - Genetic diversity for plant defense against microbial pathogens has been studied
      either by analyzing sequences of defense genes or by testing phenotypic responses
      to pathogens under experimental conditions. These two approaches give different
      but complementary information but, till date, only rare attempts at their
      integration have been made. Here we discuss the advances made, because of the two
      approaches, in understanding plant-pathogen coevolution and propose ways of
      integrating the two.

PMID- 18329330
TI  - Translational research impacting on crop productivity in drought-prone
      environments.
AB  - Conventional breeding for drought-prone environments (DPE) has been complemented
      by using exotic germplasm to extend crop gene pools and physiological approaches
      that consider water uptake (WU), water-use efficiency (WUE), and harvest index
      (HI) as drivers of yield. Drivers are associated with proxy genetic markers, such
      as carbon-isotope discrimination for WUE, canopy temperature for WU, and anthesis
      silking interval for HI in maize. Molecular markers associated with relevant
      quantitative trait loci are being developed. WUE has also been increased through
      combining understanding of root-to-shoot signaling with deficit irrigation.
      Impacts in DPE will be accelerated by combining proven technologies with
      promising new strategies such as marker-assisted selection, and genetic
      transformation, as well as conservation agriculture that can increase WU while
      averting soil degradation.

PMID- 18329331
TI  - When population genetics serves genomics: putting adaptation back in a spatial
      and historical context.
AB  - Recent advances in molecular biology have opened new perspectives for the study
      of plant adaptation, especially at the intraspecific level. Nowadays, scientists
      employing -omic results in multiple scientific fields can be optimistic of their
      chances of revealing mechanisms involved in adaptive population divergence.
      However, the investment required by integrative studies greatly reduces the
      number of experiments that can be performed. In this context, a comprehensive
      choice of accessions under study is crucial. We maintain this choice could be
      appreciably enlightened by population genetics because it helps putting adaptive
      population divergence in a spatial and historical context. As an example, we
      highlight the usefulness of knowledge about population genetic structure in the
      integrative study of metal tolerance in Arabidopsis halleri.

PMID- 18329332
TI  - Hepatozoon ursi n. sp. (Apicomplexa: Hepatozoidae) in Japanese black bear (Ursus
      thibetanus japonicus).
AB  - Morphological and genetic features of a new Hepatozoon species, Hepatozoon ursi
      n. sp., in Japanese black bear (Ursus thibetanus japonicus) were studied.
      Schizogonic developmental stages were observed in the lungs of Japanese black
      bears. The schizonts were sub-spherical in shape and 45.7+/-4.6 x 42.7+/-4.5
      microm in size. Each mature schizont contained approximately 80-130 merozoites
      and 0-5 residual bodies. The merozoites were 7.0+/-0.7 x 1.8+/-0.3 microm in
      size. Intraleukocytic gametocytes were slightly curved, cigar-like in shape and
      had a beak-like protrusion at one end. The size of the gametocytes was 10.9+/-0.3
      x 3.3+/-0.2 microm. The analyses of the18S rRNA gene sequences supported the
      hypothesis that H. ursi n. sp. is different from other Hepatozoon species. Mature
      Hepatozoon oocysts were detected in two species of ticks (Haemaphysalis japonica
      and Haemaphysalis flava) collected on the bears infected with H. ursi n. sp. Two
      measured oocysts were 263.2 x 234.0 microm and 331.8 x 231.7 microm,
      respectively. The oocysts contained approximately 40 and 50 sporocysts,
      respectively. The sporocysts were sub-spherical in shape and 31.2+/-2.5 x 27.0+/
      2.9 microm in size. Each sporocyst contained at least 8-16 sporozoites, with the
      sporozoites being 12.2+/-1.4 x 3.5+/-0.5 microm in size. H. ursi n. sp. is the
      first Hepatozoon species recorded from the family Ursidae.

PMID- 18329333
TI  - Growth, structural, optical, thermal and mechanical properties of ammonium
      pentaborate single crystal.
AB  - Nonlinear optical single crystals of ammonium pentaborate (APB) were grown by the
      slow cooling method from aqueous solution. Grown crystal was characterized by
      powder X-ray diffraction (PXRD) and FT-IR spectral analysis. Perfection of the
      grown crystal was evaluated by high-resolution X-ray diffractometry (HRXRD). The
      effect of nylon threading on the perfection of the grown bigger crystal was also
      studied by HRXRD. The range and percentage of optical transmission was
      ascertained by recording UV-vis-NIR spectrum. Thermal properties were
      investigated by TG-DTA and DSC analyses. Its mechanical hardness was estimated by
      Vickers microhardness tester.

PMID- 18329334
TI  - Theoretical calculation and vibrational spectral analysis of L-arginine
      trifluoroacetate.
AB  - Fourier transform infrared and Raman spectra of the nonlinear optical crystal, L
      arginine trifluoroacetate (L-arginine.CF3COOH, abbreviated as LATF) have been
      calculated by the first-principles calculation and investigated in experiment.
      The calculated results are slightly different from those experimental values
      because of the distinction resulted from the intermolecular hydrogen bonds. The
      role of this type of intermolecular interaction on the crystal vibrational
      spectra and nonlinear optical properties has been discussed. The absorption-edge
      on the IR side has been estimated by the theoretical approach on basis of the
      calculated infrared spectrum, which will be meaningful for further research on
      NLO crystal.

PMID- 18329335
TI  - Bioluminescence imaging to study the promoter activity of hla of Staphylococcus
      aureus in vitro and in vivo.
AB  - Alpha-toxin (Hla, encoded by hla) is a major virulence factor of Staphylococcus
      aureus. The activity of the hla promoter was analyzed using luxABCDE on an
      integration vector. The phla-lux construct was introduced in S. aureus Newman and
      its isogenic sae and sigB regulator mutants. Promoter activity was monitored by
      bioluminescence in vitro and in the murine tissue-cage model. Hla promoter
      activity could be followed in real time at repeated time points of infection. The
      activation of hla in the sigB-deficient strain and the repression to background
      levels in a sae-deficient strain relative to hla expression in the wild type
      could be demonstrated in vivo. Subinhibitory concentrations of teicoplanin,
      imipenem and ciprofloxacin enhanced hla promoter activity in vitro whereas
      clindamycin and rifampicin did not. Our approach proved to be rapid and adequate
      to study promoter activity in vitro and in vivo under conditions where high
      bacterial numbers are reached.

PMID- 18329336
TI  - Skeletal myocyte plasticity: basis for improved therapeutic potential?
AB  - Skeletal muscle tissue exhibits a remarkable capacity to regenerate after injury
      and to adapt its properties in response to altered functional demands or
      environmental pressure. This potential renders skeletal myocytes especially
      attractive candidates to be used in therapeutic strategies. Besides the well
      described adaptability of skeletal myocytes in terms of contractile function and
      metabolic profile, more recent research has revealed that the
      electrophysiological properties of myocytes are also subject to significant
      changes both under physiological conditions and in pathophysiological situations.
      A better understanding of skeletal myocyte plasticity, its regulation and its
      forced induction could improve existing therapeutic approaches and may pave the
      way for new therapeutic strategies.

PMID- 18329337
TI  - Auxiliary Ca(2+) channel subunits: lessons learned from muscle.
AB  - Voltage-gated Ca(2+) channels are multi-subunit complexes involved in many key
      functions of excitable cells. A multitude of studies in heterologous cells
      demonstrated that coexpression of the pore-forming alpha(1) subunits with
      auxiliary alpha(2)delta and beta subunits promotes membrane expression and
      modulates the biophysical channel properties. New null-mutant animal models and
      shRNA based knockdown experiments in skeletal muscle cells for the first time
      demonstrated the physiological roles and possible pathological effects of the
      alpha(2)delta-1 and beta(1a) subunits in a differentiated excitable cell. The
      alpha(2)delta-1 subunit is the determinant of the typical current properties of
      skeletal and cardiac muscle Ca(2+) channels. The beta(1a) subunit links the
      skeletal muscle Ca(2+) channel to the Ca(2+) release channel in the sarcoplasmic
      reticulum. Whether these specific functions in muscle indicate similar roles of
      alpha(2)delta and beta subunits as functional modulator and structural organizer,
      respectively, in neurons is being discussed.

PMID- 18329338
TI  - CD83 regulates lymphocyte maturation, activation and homeostasis.
AB  - The transmembrane CD83 molecule, a conserved member of the immunoglobulin
      superfamily, is known as one of the most characteristic cell surface markers for
      fully matured dendritic cells (DCs) in the peripheral circulation. An essential
      role for CD83 on murine DCs has not been found; however, evidence shows that its
      function primarily lies in the regulation of T- and B-lymphocyte maturation and
      in the regulation of their peripheral responses. Here, we review evidence for a
      role of CD83 in central lymphocyte maturation and novel, sometimes contradictory
      findings, regarding the function of CD83 in peripheral immune responses.

PMID- 18329339
TI  - The strand bias paradox of somatic hypermutation at immunoglobulin loci.
AB  - Somatic hypermutation has two phases: phase 1 affects cytosine-guanine (C/G)
      pairs and is triggered by the deamination of cytosine residues in DNA to uracil;
      phase 2 affects mostly adenine-thymine (A/T) pairs and is induced by the
      detection of uracil lesions in DNA. It is not known how, at V(D)J genes in mice,
      hypermutations accumulate at A/T pairs with strand bias without perturbing the
      strand unbiased accumulation of hypermutations at C/G pairs. Additionally, it is
      not known why, in contrast, at switch regions in mice, both C/G-targeted and A/T
      targeted hypermutations accumulate in a strand unbiased manner. To explain the
      strand bias paradox, we propose that phase 1 and phase 2 hypermutations are
      generated at different stages of the cell cycle.

PMID- 18329340
TI  - Piggybacking schistosome invasion: similarities are only skin deep.
AB  - Schistosomes cause significant morbidity and mortality. In this article, we
      discuss recent findings regarding how different schistosome species infect and
      manipulate immune responses in their hosts through the evolution and use of
      different protease classes. The advent of transgenic schistosomes is explored in
      relation to the biology of these important molecules.

PMID- 18329341
TI  - Physiology and immunology of Lepeophtheirus salmonis infections of salmonids.
AB  - 'Sea lice' is a common name for a large number of species of marine ectoparasitic
      copepods, many of which are widespread and important disease-causing agents that
      infect both cultured and wild fish. Of these copepods, the salmon louse
      Lepeophtheirus salmonis is the most extensively studied because of its economic
      impact on the salmonid aquaculture industry and its possible impacts on wild
      salmonid populations. Different levels of infection by this parasite can affect
      the long-term survival and viability of its hosts. In this article, we review the
      nature of the interactions between L. salmonis and it hosts to identify crucial
      areas that warrant further research to aid understanding of the impact of
      infection with L. salmonis.

PMID- 18329342
TI  - A hundred-year retrospective on cryptosporidiosis.
AB  - Tyzzer discovered the genus Cryptosporidium a century ago, and for almost 70
      years cryptosporidiosis was regarded as an infrequent and insignificant infection
      that occurred in the intestines of vertebrates and caused little or no disease.
      Its association with gastrointestinal illness in humans and animals was
      recognized only in the early 1980s. Over the next 25 years, information was
      generated on the disease's epidemiology, biology, cultivation, taxonomy and
      development of molecular tools. Milestones include: (i) recognition in 1980 of
      cryptosporidiosis as an acute enteric disease; (ii) its emergence as a chronic
      opportunistic infection that complicates AIDS; (iii) acknowledgement of impact on
      the water industry once it was shown to be waterborne; and (iv) study of
      Cryptosporidium genomics.

PMID- 18329343
TI  - Consequence of prior exposure to environmental mycobacteria on BCG vaccination
      and diagnosis of tuberculosis infection.
AB  - The protective efficacy of Mycobacterium bovis-bacille Calmette Guerin (BCG)
      against tuberculosis (TB) is variable in both humans and cattle. Exposure to
      environmental mycobacteria is thought to result in inappropriate priming of host
      immune responses. To investigate the impact of environmental mycobacteria on BCG
      efficacy, cattle were infected with M. avium, vaccinated with BCG, challenged
      with M. bovis and skin tested prior to necropsy. Elevated levels of IFNgamma were
      evident in M. avium-exposed animals before and after BCG vaccination with a bias
      towards avian purified protein derivative (PPD-A), suggesting that M. avium
      primed host immune responses. Exposure to M. avium also resulted in a higher
      frequency of circulatory IFNgamma-producing cells in response to PPD antigens at
      the time of M. bovis challenge. After M. bovis inoculation, the IFNgamma response
      to bovine PPD (PPD-B) increased compared to pre-challenge levels, indicating that
      all animals had been exposed to M. bovis. Skin test responses indicated 2/6 M.
      avium-BCG-M. bovis animals as reactors and 2/6 as inconclusive compared with 6/6
      BCG-M. bovis animals as reactors. M. avium-exposed animals also had fewer lesions
      and the number of tissues containing viable M. bovis at post-mortem was
      significantly lower (P<0.02 compared with BCG-M. bovis animals), with two of the
      animals described as skin test negative with no visible lesions or viable
      bacteria. Thus, exposure of cattle to environmental mycobacteria such as M. avium
      prior to BCG vaccination did not dampen BCG-specific immune responses and
      resulted in lower TB pathology. However, the PPD-A bias associated with M. avium
      exposure is likely to undermine current TB diagnostic tests and the IFNgamma test
      in cattle.

PMID- 18329345
TI  - Incidence of DNA repair deficiency disorders in western Europe: Xeroderma
      pigmentosum, Cockayne syndrome and trichothiodystrophy.
AB  - Laboratory diagnosis for DNA repair diseases has been performed in western Europe
      from the early seventies for xeroderma pigmentosum (XP) and from the mid-eighties
      for Cockayne syndrome (CS) and trichothiodystrophy (TTD). The combined data from
      the DNA repair diagnostic centres in France, (West) Germany, Italy, the
      Netherlands and the United Kingdom have been investigated for three groups of
      diseases: XP (including XP-variant), CS (including XP/CS complex) and TTD.
      Incidences in western Europe were for the first time established at 2.3 per
      million livebirths for XP, 2.7 per million for CS and 1.2 per million for TTD. As
      immigrant populations were disproportionately represented in the patients'
      groups, incidences were also established for the autochthonic western European
      population at: 0.9 per million for XP, 1.8 per million for CS and 1.1 per million
      for TTD. Perhaps contrary to general conceptions, compared to XP the incidence of
      CS appears to be somewhat higher and the incidence of TTD to be quite similar in
      the native West-European population.

PMID- 18329344
TI  - Caloric restriction: impact upon pituitary function and reproduction.
AB  - Reduced energy intake, or caloric restriction (CR), is known to extend life span
      and to retard age-related health decline in a number of different species,
      including worms, flies, fish, mice and rats. CR has been shown to reduce
      oxidative stress, improve insulin sensitivity, and alter neuroendocrine responses
      and central nervous system (CNS) function in animals. CR has particularly
      profound and complex actions upon reproductive health. At the reductionist level
      the most crucial physiological function of any organism is its capacity to
      reproduce. For a successful species to thrive, the balance between available
      energy (food) and the energy expenditure required for reproduction must be
      tightly linked. An ability to coordinate energy balance and fecundity involves
      complex interactions of hormones from both the periphery and the CNS and
      primarily centers upon the master endocrine gland, the anterior pituitary. In
      this review article we review the effects of CR on pituitary gonadotrope function
      and on the male and female reproductive axes. A better understanding of how
      dietary energy intake affects reproductive axis function and endocrine
      pulsatility could provide novel strategies for the prevention and management of
      reproductive dysfunction and its associated comorbidities.

PMID- 18329346
TI  - Determination of citrulline in human plasma, red blood cells and urine by
      electron impact (EI) ionization gas chromatography-mass spectrometry.
AB  - A method was developed by using gas chromatography-mass spectrometry in the
      electron impact ionization mode to quantify citrulline in plasma, red blood cells
      (RBC) and urine. For all three fluids, citrulline was extracted on ion exchange
      resins, before derivatization to its propyl-heptaflorobutyryl-ester. Assay
      precision (coefficient of variation, CV) was <5%, recovery% was >90% and the
      within- and between-day CV were <10% on 200 microL of plasma and RBC, and 400
      microL of urine. The current method allows for the detection of 20 pmol of
      natural citrulline in aqueous standards, and small volumes (<100 microL) of
      biological fluids.

PMID- 18329347
TI  - Differential liquid phase proteomic analysis of the effect of selenium
      supplementation in LNCaP cells.
AB  - The effect of 100 nM sodium selenite supplementation was studied on LNCaP cells
      by a proteomic approach, on ProteomeLab PF 2D platform. Proteins were separated
      by liquid phase bi-dimensional chromatography and analyzed by pair-wise alignment
      of peaks to detect those differentially expressed. Differential expression
      threshold was set at a twice difference level and proteins matching this
      criterion were identified by MALDI-TOF and confirmed by ESI-ion trap MS/MS. Not
      all differentially expressed proteins found by PF 2D could be identified by MS
      analysis, the sensitivity of which emerging as the limiting factor. Thus, only
      the most abundant proteins, differently expressed following selenium
      supplementation, were identified. We positively showed an increase of expression
      of thioredoxin reductase 1, enolase 1, phosphoglycerate mutase 1, glyceraldehyde
      3-phosphate dehydrogenase, heterogeneous nuclear ribonucleoprotein A2/B1, isoform
      A2, Ras-GTPase-activating protein SH3-domain-binding protein and Keratin 18 and a
      decrease of expression of peroxiredoxin 1 and heat shock protein 70, protein 8,
      isoform 1. Results are consistent, at least in part, with the less oxidant
      environment brought about by the synthesis of Se-dependent peroxidases, keeping
      low the steady-state concentration of hydrogen peroxide.

PMID- 18329348
TI  - A stimulus-responsive magnetic nanoparticle drug carrier: magnetite encapsulated
      by chitosan-grafted-copolymer.
AB  - We describe a magnetic nanoparticle drug carrier for controlled drug release that
      responds to the change in external temperature or pH, with characteristics of
      longer circulation time and reduced side effects. The novel nanocarrier is
      characterized by a functionalized magnetite (Fe(3)O(4)) core that is conjugated
      with drug via acid-labile hydrazone-bond and encapsulated by the thermosensitive
      smart polymer, chitosan-g-poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)
      [chitosan-g-poly(NIPAAm-co-DMAAm)]. The chitosan-g-poly(NIPAAm-co-DMAAm) smart
      polymer exhibits a lower critical solution temperature (LCST) of approximately 38
      degrees C, signifying phase transition behavior of the smart polymer and enabling
      its use for triggering on-off mechanisms. The drug release response was
      appreciably low at a temperature less than the LCST as compared with a
      temperature above the LCST. In each case, there was an initial rapid drug
      release, followed by a controlled released in the second stage, especially in a
      mild acidic buffer solution of pH 5.3. We believe that the drug release occurs
      via a collapse of the encapsulated thermosensitive polymer and cleavage of the
      acid-labile hydrazone linkage.

PMID- 18329349
TI  - VATS pericardiotomy for patients with known malignancy and pericardial effusion:
      survival and prognosis of positive cytology and metastatic involvement of the
      pericardium: a case control study.
AB  - BACKGROUND: Pericardiotomy for cancer patients with effusion can alleviate
      symptoms, but with unclear effect on long term survival. Our experience with VATS
      technique has produced some long-term survivors. METHODS: A retrospective review
      of 62 VATS pericardiotomy for pericardial effusion in patients with known
      malignancy. Kaplan-Meier survival curves and Log-Rank tests were used for
      analysis. RESULTS: The mean age was 54.8+/-14.3 years (ranging from 19 to 79).
      The mean hospital stay was 8.7+/-5.5 days. The median survival was 6.75 months
      (range 1 month-10 years). Overall one-year survival was 44.2%, 3-year survival
      17.6%, and 5-year survival 10% after drainage of pericardial effusion. The mean
      survival in cytology negative patients (n=21) was 13.4+/-0.98 months, compared to
      4.89+/-0.9 months in cytology positive patients (n=27) (p=0.0175). The 5-year
      survival in cytology negative patients was 19.6%, while none of the patients with
      positive cytology were alive after 36 months. The mean survival in patients with
      no evidence of metastatic disease on the pericardium (n=28) was 12.8+/-0.9
      months, compared to patients with metastatic disease of the pericardium (n=22)
      4.66+/-0.8 months (p=0.026). CONCLUSIONS: VATS Pericardiotomy can provide
      effective long-term drainage in patients with symptomatic pericardial effusion.
      Positive cytology and metastatic involvement of the pericardium are predictive of
      worse survival. Survival greater than 5 years can be expected in 19% and 17% of
      patients with negative fluid cytology and negative metastatic disease of the
      pericardium, respectively.

PMID- 18329350
TI  - Osteocutaneous face transplantation.
AB  - BACKGROUND: Facial transplantation has the potential to become a viable option in
      the treatment of acquired and congenital facial deformities. Transplantation of
      the bony maxillofacial skeleton with the soft tissues (osteocutaneous face
      transplantation) has not been performed clinically nor has it been described
      experimentally in a human cadaver model. METHODS: A mock osteocutaneous face
      transplant procedure was carried out on a cadaver model. The face was harvested
      in the subperiosteal plane and included the Le Fort III osseous segment. The
      allograft was inset by rigid internal fixation and soft tissue approximation.
      RESULTS: The face transplant procedure was technically feasible. On the basis of
      this experiment, review of prior investigations, and our experience in
      craniofacial surgery, the authors have identified 10 topics that present
      technical challenges specific to osteocutaneous transplantation of the face:
      customisation of the bony segment, sensory and motor innervation, extra-ocular
      movements, dentition, mastication, speech and swallowing, airway, vascular
      considerations, immunologic considerations, and identity issues. CONCLUSIONS:
      Once further advances in immunomodulatory therapy are made, face transplantation
      will likely still be reserved for only the most severe facial defects. Defects of
      such severity will likely include a substantial bony component in need of
      reconstruction. In addition to the challenges associated with facial allo
      transplantation in general, there are many technical challenges associated
      specifically with osteocutaneous face transplantation. It is necessary to
      consider and discuss these challenges in anticipation of future advances that may
      allow composite face transplantation to become safe and clinically efficacious.
      This modality of transplantation has the potential to provide substantial benefit
      compared with autologous reconstruction.

PMID- 18329351
TI  - Referral pattern and surgical outcome of sagittal synostosis.
AB  - SUMMARY: Sagittal synostosis (SS) is the commonest form of craniosynostosis, and
      in the Birmingham Craniofacial Unit has been preferably managed by strip
      craniectomy when the baby is under 6 months of age or calvarial remodelling when
      over 6 months old. The unit uses cephalic index (CI) as an objective measure of
      head shape. This retrospective study analysed referral patterns and the
      correlation between age at operation and CI. Patients' unit notes and images of
      47 patients referred for SS between July 1999 and December 2003 were reviewed.
      Thirty-three non-syndromic SS patients were studied and demographics, referral
      information and preoperative and postoperative CI measurements were recorded.
      Paediatricians referred 91% (mean age 15 months) of cases and general
      practitioners 9% (all beyond 6 months). There was a significant difference
      between pre- and postoperative CI for patients operated at less than 12 months
      (P=0.02). No difference was demonstrated for patients operated at greater than 12
      months. CONCLUSION: Early surgery for SS was associated with a better aesthetic
      result in this series, although CI may be a crude form of head shape analysis.
      Later referral was associated with a more complex referral pathway. A fast track
      system for general practitioners and paediatricians to aid early referrals may
      improve surgical outcome.

PMID- 18329352
TI  - [Waiting lists for kidney transplantation: another reason for early nephrological
      care of chronic-kidney disease patients].

PMID- 18329353
TI  - [FINEs, French intradialytic nutrition evaluation study].

PMID- 18329354
TI  - Body composition and bone density in Canadian White and Aboriginal women: the
      First Nations Bone Health Study.
AB  - Ethnic variation in soft tissue composition may contribute to observed ethnic
      differences in bone mineral density (BMD). This analysis was performed to
      determine whether ethnic differences in body composition affect differences in
      BMD between Canadian White and Aboriginal women. An age-stratified population
      based sample of 206 Aboriginal women and 177 White women underwent multisite bone
      density measurements and total body soft tissue composition analysis. In
      univariate analyses, each kg of additional lean mass was associated with a
      greater increase in BMD than an equal amount of fat mass (p<.01). When models
      simultaneously evaluated both soft tissue measurements, lean mass (but not fat
      mass) was positively correlated with BMD at all measurement sites (p<.001).
      Aboriginal women had significantly lower weight-adjusted BMD than White women for
      two sites (calcaneus, p = .019; total body, p = .026) and lower BMI-adjusted for
      BMD three sites (calcaneus, p = .0076; distal forearm, p = .047; total body, p =
      .022). The ratio of lean mass to fat mass was lower in Aboriginal than White
      women (p<.001). When BMD was adjusted for body composition variables no
      significant difference was seen between Aboriginal and White women. Apparent
      ethnic differences in weight- and BMI-adjusted BMD between Canadian White and
      Aboriginal women were explained by a lower ratio of lean mass to fat mass in
      Aboriginal women, combined with a smaller increment in BMD from fat mass versus
      lean mass in both populations.

PMID- 18329355
TI  - Vitamin D status in postmenopausal women living at higher latitudes in the UK in
      relation to bone health, overweight, sunlight exposure and dietary vitamin D.
AB  - For 5 months a year the UK has insufficient sunlight for cutaneous synthesis of
      vitamin D and winter requirements are met from stores made the previous summer.
      Although there are few natural dietary sources, dietary intake may help maintain
      vitamin D status. We investigated the relationship between 25-hydroxyvitamin D
      (25(OH)D), bone health, overweight, sunlight exposure and dietary vitamin D in
      3113 women (age 54.8 [SD 2.3] years) living at latitude 57 degrees N between 1998
      2000. Serum 25(OH)D was measured by high performance liquid chromatography
      (HPLC), dietary intakes (food frequency questionnaire, n=2598), sunlight exposure
      (questionnaire, n=2402) and bone markers were assessed. Bone mineral density
      (BMD) was measured by dual x-ray absorptiometry in all women at the sampling
      visit and 6 years before. Seasonal variation in 25(OH)D was not substantial with
      a peak in the autumn (23.7 [9.9] ng/ml) and a nadir in spring (19.7 [7.6] ng/ml).
      Daily intake of vitamin D was 4.2 [2.5] mug from food only and 5.8 [4.0] mug
      including vitamin D from cod liver oil and multivitamins. The latter was
      associated with 25(OH)D at each season whereas vitamin D simply from food was
      associated with 25(OH)D in winter and spring only. Sunlight exposure was
      associated with 25(OH)D in summer and autumn. 25(OH)D was negatively associated
      with increased bone resorption and bone loss (P<0.05) remaining significant after
      adjustment for confounders (age, weight, height, menopausal status/HRT use,
      physical activity and socio-economic status). Using an insufficiency cut-off of
      <28 ng/ml 25(OH)D, showed lower concentrations of bone resorption markers in the
      upper category (fDPD/Cr 5.1 [1.7] nmol/mmol compared to 5.3 [2.1] nmol/mmol,
      P=0.03) and no difference in BMD or bone loss. 25(OH)D was lower (P<0.01) and
      parathyroid hormone higher (P<0.01) in the top quintile of body mass index. In
      conclusion, low vitamin D status is associated with greater bone turnover, bone
      loss and obesity. Diet appears to attenuate the seasonal variation of vitamin D
      status in early postmenopausal women at northerly latitude where quality of
      sunlight for production of vitamin D is diminished.

PMID- 18329356
TI  - Next-generation sequencing: the race is on.
AB  - The $1000 genome may still be years away, but with the arrival of next-generation
      sequencing (NGS) technologies that are much faster and cheaper than the
      traditional Sanger method, large-scale sequencing of hundreds or even thousands
      of human genomes is fast becoming reality.

PMID- 18329357
TI  - Flexible scaffolding made of rigid BARs.
AB  - Crescent-shaped BAR domains are generic actors in the creation of membrane
      curvature. In this issue, Frost et al. (2008) reveal how collective twisting of
      rigid F-BAR domains on a soft membrane surface may lead to different membrane
      curvatures.

PMID- 18329358
TI  - Wnt signaling in the niche.
AB  - There is much interest in understanding the signals in the bone marrow niche that
      keep hematopoietic stem cells (HSCs) in a quiescent state. In the current issue
      of Cell Stem Cell, Fleming et al. (2008) report that blocking Wnt signaling in
      the niche increases the number of proliferating HSCs and reduces their ability to
      reconstitute the hematopoietic system of irradiated recipient mice. These
      findings show that Wnt/beta-catenin activity is crucial for the maintenance of
      HSC quiescence in the bone marrow niche.

PMID- 18329359
TI  - Hop1 and the meiotic DNA-damage response.
AB  - During the DNA-damage response, adaptor proteins mediate signaling between the
      PI3K-like sensor kinases, ATM and ATR, and serine/threonine effector kinases.
      Carballo et al. (2008) now show that the chromosomal protein Hop1 mediates PI3K
      like kinase signaling during the repair of DNA double-strand breaks (DSBs) in
      meiosis.

PMID- 18329360
TI  - Synaptic asymmetry to go.
AB  - Cell polarity is critical for T lymphocyte movement during their hunt for antigen
      bearing cells and for infected target cells. In this issue of Cell, Yeh et al.
      (2008) now reveal a direct link between T cell polarity and the production of
      proinflammatory cytokines in mice lacking the class I MHC-restricted T cell
      associated molecule (Crtam).

PMID- 18329361
TI  - Cellular programming of plant gene imprinting.
AB  - Gene imprinting, the differential expression of maternal and paternal alleles,
      independently evolved in mammals and in flowering plants. A unique feature of
      flowering plants is a double-fertilization event in which the sperm fertilize not
      only the egg, which forms the embryo, but also the central cell, which develops
      into the endosperm (an embryo-supporting tissue). The distinctive mechanisms of
      gene imprinting in the endosperm, which involve DNA demethylation and histone
      methylation, begin in the central cell and sperm prior to fertilization.
      Flowering plants might have coevolved double fertilization and imprinting to
      prevent parthenogenetic development of the endosperm.

PMID- 18329362
TI  - C. elegans telomeres contain G-strand and C-strand overhangs that are bound by
      distinct proteins.
AB  - Single-strand extensions of the G strand of telomeres are known to be critical
      for chromosome-end protection and length regulation. Here, we report that in C.
      elegans, chromosome termini possess 3' G-strand overhangs as well as 5' C-strand
      overhangs. C tails are as abundant as G tails and are generated by a well
      regulated process. These two classes of overhangs are bound by two single
      stranded DNA binding proteins, CeOB1 and CeOB2, which exhibit specificity for G
      rich or C-rich telomeric DNA. Strains of worms deleted for CeOB1 have elongated
      telomeres as well as extended G tails, whereas CeOB2 deficiency leads to telomere
      length heterogeneity. Both CeOB1 and CeOB2 contain OB (oligo-saccharide/oligo
      nucleotide binding) folds, which exhibit structural similarity to the second and
      first OB folds of the mammalian telomere binding protein hPOT1, respectively. Our
      results suggest that C. elegans telomere homeostasis relies on a novel mechanism
      that involves 5' and 3' single-stranded termini.

PMID- 18329363
TI  - Phosphorylation of the axial element protein Hop1 by Mec1/Tel1 ensures meiotic
      interhomolog recombination.
AB  - An essential feature of meiosis is interhomolog recombination whereby a
      significant fraction of the programmed meiotic double-strand breaks (DSBs) is
      repaired using an intact homologous non-sister chromatid rather than a sister.
      Involvement of Mec1 and Tel1, the budding yeast homologs of the mammalian ATR and
      ATM kinases, in meiotic interhomlog bias has been implicated, but the mechanism
      remains elusive. Here, we demonstrate that Mec1 and Tel1 promote meiotic
      interhomolog recombination by targeting the axial element protein Hop1. Without
      Mec1/Tel1 phosphorylation of Hop1, meiotic DSBs are rapidly repaired via a Dmc1
      independent intersister repair pathway, resulting in diminished interhomolog
      crossing-over leading to spore lethality. We find that Mec1/Tel1-mediated
      phosphorylation of Hop1 is required for activation of Mek1, a meiotic paralogue
      of the DNA-damage effector kinase, Rad53p/CHK2. Thus, Hop1 is a meiosis-specific
      adaptor protein of the Mec1/Tel1 signaling pathway that ensures interhomolog
      recombination by preventing Dmc1-independent repair of meiotic DSBs.

PMID- 18329364
TI  - Kid-mediated chromosome compaction ensures proper nuclear envelope formation.
AB  - Toward the end of mitosis, neighboring chromosomes gather closely to form a
      compact cluster. This is important for reassembling the nuclear envelope around
      the entire chromosome mass but not individual chromosomes. By analyzing mice and
      cultured cells lacking the expression of chromokinesin Kid/kinesin-10, we show
      that Kid localizes to the boundaries of anaphase and telophase chromosomes and
      contributes to the shortening of the anaphase chromosome mass along the spindle
      axis. Loss of Kid-mediated anaphase chromosome compaction often causes the
      formation of multinucleated cells, specifically at oocyte meiosis II and the
      first couple of mitoses leading to embryonic death. In contrast, neither male
      meiosis nor somatic mitosis after the morula-stage is affected by Kid deficiency.
      These data suggest that Kid-mediated anaphase/telophase chromosome compaction
      prevents formation of multinucleated cells. This protection is especially
      important during the very early stages of development, when the embryonic cells
      are rich in ooplasm.

PMID- 18329365
TI  - The evolution of gene regulation underlies a morphological difference between two
      Drosophila sister species.
AB  - Understanding the mechanisms underlying the morphological divergence of species
      is one of the central goals of evolutionary biology. Here, we analyze the genetic
      and molecular bases of the divergence of body pigmentation patterns between
      Drosophila yakuba and its sister species Drosophila santomea. We found that loss
      of pigmentation in D. santomea involved the selective loss of expression of the
      tan and yellow pigmentation genes. We demonstrate that tan gene expression was
      eliminated through the mutational inactivation of one specific tan cis-regulatory
      element (CRE) whereas the Tan protein sequence remained unchanged. Surprisingly,
      we identify three independent loss-of-function alleles of the tan CRE in the
      young D. santomea lineage. We submit that there is sufficient empirical evidence
      to support the general prediction that functional evolutionary changes at
      pleiotropic loci will most often involve mutations in their discrete, modular cis
      regulatory elements.

PMID- 18329366
TI  - Tyrosine kinases Btk and Tec regulate osteoclast differentiation by linking RANK
      and ITAM signals.
AB  - Certain autoimmune diseases result in abnormal bone homeostasis, but association
      of immunodeficiency with bone is poorly understood. Osteoclasts, which derive
      from bone marrow cells, are under the control of the immune system.
      Differentiation of osteoclasts is mainly regulated by signaling pathways
      activated by RANK and immune receptors linked to ITAM-harboring adaptors.
      However, it is unclear how the two signals merge to cooperate in osteoclast
      differentiation. Here we report that mice lacking the tyrosine kinases Btk and
      Tec show severe osteopetrosis caused by a defect in bone resorption. RANK and
      ITAM signaling results in formation of a Btk(Tec)/BLNK(SLP-76)-containing complex
      and PLCgamma-mediated activation of an essential calcium signal. Furthermore, Tec
      kinase inhibition reduces osteoclastic bone resorption in models of osteoporosis
      and inflammation-induced bone destruction. Thus, this study reveals the
      importance of the osteoclastogenic signaling complex composed of tyrosine
      kinases, which may provide the molecular basis for a new therapeutic strategy.

PMID- 18329367
TI  - Structural basis of membrane invagination by F-BAR domains.
AB  - BAR superfamily domains shape membranes through poorly understood mechanisms. We
      solved structures of F-BAR modules bound to flat and curved bilayers using
      electron (cryo)microscopy. We show that membrane tubules form when F-BARs
      polymerize into helical coats that are held together by lateral and tip-to-tip
      interactions. On gel-state membranes or after mutation of residues along the
      lateral interaction surface, F-BARs adsorb onto bilayers via surfaces other than
      their concave face. We conclude that membrane binding is separable from membrane
      bending, and that imposition of the module's concave surface forces fluid-phase
      bilayers to bend locally. Furthermore, exposure of the domain's lateral
      interaction surface through a change in orientation serves as the crucial trigger
      for assembly of the helical coat and propagation of bilayer bending. The
      geometric constraints and sequential assembly of the helical lattice explain how
      F-BAR and classical BAR domains segregate into distinct microdomains, and provide
      insight into the spatial regulation of membrane invagination.

PMID- 18329368
TI  - Active caspase-1 is a regulator of unconventional protein secretion.
AB  - Mammalian cells export most proteins by the endoplasmic reticulum/Golgi-dependent
      pathway. However, some proteins are secreted via unconventional, poorly
      understood mechanisms. The latter include the proinflammatory cytokines
      interleukin(IL)-1beta, IL-18, and IL-33, which require activation by caspase-1
      for biological activity. Caspase-1 itself is activated by innate immune
      complexes, the inflammasomes. Here we show that secretion of the leaderless
      proteins proIL-1alpha, caspase-1, and fibroblast growth factor (FGF)-2 depends on
      caspase-1 activity. Although proIL-1alpha and FGF-2 are not substrates of the
      protease, we demonstrated their physical interaction. Secretome analysis using
      iTRAQ proteomics revealed caspase-1-mediated secretion of other leaderless
      proteins with known or unknown extracellular functions. Strikingly, many of these
      proteins are involved in inflammation, cytoprotection, or tissue repair. These
      results provide evidence for an important role of caspase-1 in unconventional
      protein secretion. By this mechanism, stress-induced activation of caspase-1
      directly links inflammation to cytoprotection, cell survival, and regenerative
      processes.

PMID- 18329369
TI  - Final stages of cytokinesis and midbody ring formation are controlled by BRUCE.
AB  - Cytokinesis involves the formation of a cleavage furrow, followed by abscission,
      the cutting of the midbody channel, the final bridge between dividing cells.
      Recently, the midbody ring became known as central for abscission, but its
      regulation remains enigmatic. Here, we identify BRUCE, a 528 kDa multifunctional
      protein, which processes ubiquitin-conjugating activity, as a major regulator of
      abscission. During cytokinesis, BRUCE moves from the vesicular system to the
      midbody ring and serves as a platform for the membrane delivery machinery and
      mitotic regulators. Depletion of BRUCE in cell cultures causes defective
      abscission and cytokinesis-associated apoptosis, accompanied by a block of
      vesicular targeting and defective formation of the midbody and the midbody ring.
      Notably, ubiquitin relocalizes from midbody microtubules to the midbody ring
      during cytokinesis, and depletion of BRUCE disrupts this process. We propose that
      BRUCE coordinates multiple steps required for abscission and that ubiquitylation
      may be a crucial trigger.

PMID- 18329370
TI  - Regulation of a late phase of T cell polarity and effector functions by Crtam.
AB  - Spatial organization of cellular proteins plays an important role in
      establishment of cellular polarity to regulate cell division, differentiation,
      migration, and organogenesis. Activation of T cells by antigen-presenting cells
      (APCs) results in the formation of an immunological synapse (IS), assembly of a
      signaling scaffold at the T cell receptor (TCR) contact, cytoskeletal
      reorganization, and generation of second messengers within the first hours
      following intercellular contact. We demonstrate here that Crtam (class-I MHC
      restricted T-cell associated molecule), an immunoglobulin-superfamily
      transmembrane protein, coordinates a signaling complex anchored by the Scrib
      polarity protein to establish a later phase of T cell polarity on a subset of
      CD4+ T cells >6 hours following activation. Maintenance of this late cellular
      polarity results in the ability of CD4+Crtam+ T cells to selectively produce more
      IFNgamma and IL22. Crtam engagement thus modulates signals many hours beyond the
      initial activation event and dynamically influences the adaptive immune response.

PMID- 18329371
TI  - Dicer ablation affects antibody diversity and cell survival in the B lymphocyte
      lineage.
AB  - To explore the role of Dicer-dependent control mechanisms in B lymphocyte
      development, we ablated this enzyme in early B cell progenitors. This resulted in
      a developmental block at the pro- to pre-B cell transition. Gene-expression
      profiling revealed a miR-17 approximately 92 signature in the 3'UTRs of genes
      upregulated in Dicer-deficient pro-B cells; a top miR-17 approximately 92 target,
      the proapoptotic molecule Bim, was highly upregulated. Accordingly, B cell
      development could be partially rescued by ablation of Bim or transgenic
      expression of the prosurvival protein Bcl-2. This allowed us to assess the impact
      of Dicer deficiency on the V(D)J recombination program in developing B cells. We
      found intact Ig gene rearrangements in immunoglobulin heavy (IgH) and kappa chain
      loci, but increased sterile transcription and usage of D(H) elements of the DSP
      family in IgH, and increased N sequence addition in Igkappa due to deregulated
      transcription of the terminal deoxynucleotidyl transferase gene.

PMID- 18329372
TI  - Targeted deletion reveals essential and overlapping functions of the miR-17
      through 92 family of miRNA clusters.
AB  - miR-17 approximately 92, miR-106b approximately 25, and miR-106a approximately
      363 belong to a family of highly conserved miRNA clusters. Amplification and
      overexpression of miR-1792 is observed in human cancers, and its oncogenic
      properties have been confirmed in a mouse model of B cell lymphoma. Here we show
      that mice deficient for miR-17 approximately 92 die shortly after birth with lung
      hypoplasia and a ventricular septal defect. The miR-17 approximately 92 cluster
      is also essential for B cell development. Absence of miR-17 approximately 92
      leads to increased levels of the proapoptotic protein Bim and inhibits B cell
      development at the pro-B to pre-B transition. Furthermore, while ablation of miR
      106b approximately 25 or miR-106a approximately 363 has no obvious phenotypic
      consequences, compound mutant embryos lacking both miR-106b approximately 25 and
      miR-17 approximately 92 die at midgestation. These results provide key insights
      into the physiologic functions of this family of microRNAs and suggest a link
      between the oncogenic properties of miR-17 approximately 92 and its functions
      during B lymphopoiesis and lung development.

PMID- 18329373
TI  - Dynamic regulation of nucleosome positioning in the human genome.
AB  - The positioning of nucleosomes with respect to DNA plays an important role in
      regulating transcription. However, nucleosome mapping has been performed for only
      limited genomic regions in humans. We have generated genome-wide maps of
      nucleosome positions in both resting and activated human CD4+ T cells by direct
      sequencing of nucleosome ends using the Solexa high-throughput sequencing
      technique. We find that nucleosome phasing relative to the transcription start
      sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore,
      the first nucleosome downstream of a start site exhibits differential positioning
      in active and silent genes. TCR signaling induces extensive nucleosome
      reorganization in promoters and enhancers to allow transcriptional activation or
      repression. Our results suggest that H2A.Z-containing and modified nucleosomes
      are preferentially lost from the -1 nucleosome position. Our data provide a
      comprehensive view of the nucleosome landscape and its dynamic regulation in the
      human genome.

PMID- 18329374
TI  - SnapShot: cytokines III.

PMID- 18329375
TI  - Oxidation of alkyl nitronates catalyzed by 2-nitropropane dioxygenase from
      Hansenula mrakii.
AB  - 2-Nitropropane dioxygenase from Hansenula mrakii was expressed in Escherichia
      coli cells and purified in active and stable form using 60% saturation of
      ammonium sulfate and a single chromatographic step onto a DEAE column. MALDI-TOF
      mass spectrometric and spectrophotometric analyses of the flavin extracted by
      heat or acid denaturation of the enzyme indicated that FMN, and not FAD as
      erroneously reported previously, is present in a 1:1 stoichiometry with the
      protein. Inductively coupled plasma mass spectrometric analysis of the enzyme
      established that H. mrakii 2-nitropropane dioxygenase contains negligible amounts
      of iron, manganese, zinc, and copper ions, which are not catalytically relevant.
      Anaerobic substrate reduction and kinetic data using a Clark oxygen electrode to
      measure rates of oxygen consumption indicated that the enzyme is active on a
      broad range of alkyl nitronates, with a marked preference for unbranched
      substrates over propyl-2-nitronate. Interestingly, the enzyme reacts poorly, if
      at all, with nitroalkanes, as suggested by lack of both anaerobic reduction of
      the enzyme-bound flavin and consumption of oxygen with nitroethane, nitrobutane,
      and 2-nitropropane. Finally, both the tight binding of sulfite (K(d)=90 microM,
      at pH 8 and 15 degrees C) to the enzyme and the formation of the anionic
      flavosemiquinone upon anaerobic incubation with alkyl nitronates are consistent
      with the presence of a positively charged group in proximity of the N1-C2=O atoms
      of the FMN cofactor.

PMID- 18329376
TI  - Nucleolar targeting of proteins by the tandem array of basic amino acid stretches
      identified in the RNA polymerase I-associated factor PAF49.
AB  - There is accumulating evidence to indicate that the regulation of subnuclear
      compartmentalization plays important roles in cellular processes. The RNA
      polymerase I-associated factor PAF49 has been shown to accumulate in the
      nucleolus in growing cells, but disperse into the nucleoplasm in growth-arrested
      cells. Serial deletion analysis revealed that amino acids 199-338 were necessary
      for the nucleolar localization of PAF49. Combinatorial point mutation analysis
      indicated that the individual basic amino acid stretches (BS) within the central
      (BS1-4) and the C-terminal (BS5 and 6) regions may cooperatively confer the
      nucleolar localization of PAF49. Addition of the basic stretches in tandem to a
      heterologous protein, such as the interferon regulatory factor-3, translocated
      the tagged protein into the nucleolus, even in the presence of an intrinsic
      nuclear export sequence. Thus, tandem array of the basic amino acid stretches
      identified here functions as a dominant nucleolar targeting sequence.

PMID- 18329377
TI  - Synthesis of gamma-glutamylcysteine as a major low-molecular-weight thiol in
      lactic acid bacteria Leuconostoc spp.
AB  - Some members of lactic acid bacteria are known to synthesize glutathione (GSH) or
      to import it from growth medium, whereas others are not. Analysis of the genome
      sequences of several Leuconostoc spp. indicate the presence of the gene gshA that
      encodes gamma-glutamylcysteine synthetase, but not the gene gshB encoding
      glutathione synthetase. We report here that, in cells of Leuconostoc kimchii and
      Leuconostoc mesenteroides, gamma-glutamylcysteine (gamma-GC) is present in large
      amount, whereas GSH is not detectable. The level of gamma-GC was higher at the
      stationary phase than at the exponential phase. Expression of the gshA gene in
      Leuconostoc spp. analyzed by S1 mapping showed the increased mRNA level upon
      hydrogen peroxide treatment. From high-resolution S1 mapping, the transcriptional
      start site was mapped and the putative promoter elements were suggested. This
      work suggests that gamma-GC has a significant role in Leuconostoc spp. as the
      major low-molecular-weight thiol.

PMID- 18329378
TI  - Crystal structure studies on sulfur oxygenase reductase from Acidianus
      tengchongensis.
AB  - Sulfur oxygenase reductase (SOR) simultaneously catalyzes oxidation and reduction
      of elemental sulfur to produce sulfite, thiosulfate, and sulfide in the presence
      of molecular oxygen. In this study, crystal structures of wild type and mutants
      of SOR from Acidianus tengchongensis (SOR-AT) in two different crystal forms were
      determined and it was observed that 24 identical SOR monomers form a hollow
      sphere. Within the icosatetramer sphere, the tetramer and trimer channels were
      proposed as the paths for the substrate and products, respectively. Moreover, a
      comparison of SOR-AT with SOR-AA (SOR from Acidianus ambivalens) structures
      showed that significant differences existed at the active site. Firstly, Cys31 is
      not persulfurated in SOR-AT structures. Secondly, the iron atom is five
      coordinated rather than six-coordinated, since one of the water molecules ligated
      to the iron atom in the SOR-AA structure is lost. Consequently, the binding sites
      of substrates and a hypothetical catalytic process of SOR were proposed.

PMID- 18329379
TI  - Enhanced BMP signaling results in supernumerary tooth formation in USAG-1
      deficient mouse.
AB  - Uterine sensitization associated gene-1 (USAG-1) is a BMP antagonist, and also
      modulates Wnt signaling. We previously reported that USAG-1 deficient mice have
      supernumerary teeth. The supernumerary maxillary incisor appears to form as a
      result of the successive development of the rudimentary upper incisor. USAG-1
      abrogation rescued apoptotic elimination of odontogenic mesenchymal cells. We
      confirmed that BMPs were expressed in both the epithelium and mesenchyme of the
      rudimentary incisor at E14 and E15. BMP signaling in the rudimentary maxillary
      incisor, assessed by expressions of Msx1 and Dlx2 and the phosphorylation of Smad
      protein, was significantly enhanced. Wnt signaling as demonstrated by the nuclear
      localization of beta-catenin was also up-regulated. Inhibition of BMP signaling
      rescues supernumerary tooth formation in E15 incisor explant culture. Based upon
      these results, we conclude that enhanced BMP signaling results in supernumerary
      teeth and BMP signaling was modulated by Wnt signaling in the USAG-1 deficient
      mouse model.

PMID- 18329380
TI  - Characterization of fibrillation process of alpha-synuclein at the initial stage.
AB  - alpha-Synuclein is the major component of the filamentous Lewy bodies and Lewy
      related neurites, neuropathological hallmarks of Parkinson's disease. Although
      numerous studies on alpha-synuclein fibrillation have been reported, the
      molecular mechanisms of aggregation and fibrillation at the initial stage are
      still unclear. In the present study, structural properties and propensities to
      form fibrils of alpha-synuclein at the initial stage were investigated using 2D
      (1)H-(15)N NMR spectroscopy, electron microscope, and small angle X-ray
      scattering (SAXS). Observation of the 2D (1)H-(15)N HSQC spectra indicated
      significant attenuation of many cross peak intensities in the regions of KTKEGV
      type repeats and the non-Abeta component of Alzheimer's disease amyloid (NAC),
      suggesting that these regions contributed fibril formation. Oligomerization
      comprising heptamer was successfully monitored at the initial stage using the
      time-dependent SAXS measurements.

PMID- 18329381
TI  - Inhibitory effect of obestatin on glucose-induced insulin secretion in rats.
AB  - Obestatin is a bioactive peptide encoded by the same gene that encodes ghrelin.
      Our aim was to investigate the effect of obestatin on insulin secretion. We
      evaluated the effects of obestatin on insulin secretion from rat islet cells
      which had been incubated overnight in the presence of 8.3, 11.1, and 22.2 mmol/l
      of glucose. In vivo, the serum levels of glucose and insulin were measured 0, 1,
      5, 10, 20, 40, and 60 min after the intravenous administration of saline or
      glucose (1g/kg), with or without obestatin, and the area under the 60 min curve
      of insulin concentration (AUC(insulin)) was calculated. Obestatin (0.01-100
      nmol/l) inhibited insulin secretion from rat islets in a dose-dependent fashion.
      In vivo, when administered intravenously to rats together with glucose, obestatin
      (10, 50, and 250 nmol/kg) inhibited both the rapid 1-min insulin response and the
      AUC(insulin) in a dose-dependent fashion. Our data demonstrate that under glucose
      stimulated conditions, exogenous obestatin acts as a potent inhibitor of insulin
      secretion in anaesthetized rats in vivo as well as in cultured islets in vitro.

PMID- 18329382
TI  - HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered
      with Talabostat.
AB  - Selection of potent yet low reactogenic adjuvants for protein immunization is
      important for HIV-1 vaccine development. Immunogenicity of electroporated DNA
      (HIV env) and recombinant gp120, administered with either QS-21 or the orally
      administered immunomodulator, Talabostat, was evaluated in BALB/c mice.
      Electroporation of low dose DNA elicited Th1 cytokines and anti-envelope
      antibodies. Immunization with gp120 protein alone with or without Talabostat
      elicited lower Th1 and Th2 cytokine levels but comparable anti-gp120 antibodies
      to QS-21-formulated protein. Boosting of DNA-primed mice with gp120/Talabostat
      induced similar anti-gp120 antibody titers and slightly higher levels of Th1 and
      Th2 cytokines relative to QS-21-formulated protein. Induction of CD8(+) and
      CD4(+) T cells and functional CTL activity was noted. These results highlight the
      potential use of orally administered Talabostat for efficient protein boosting of
      antibody and T-cell responses primed by DNA.

PMID- 18329383
TI  - Increased expression of highly sulfated keratan sulfate synthesized in malignant
      astrocytic tumors.
AB  - Keratan sulfate (KS) proteoglycans are expressed on a subpopulation of microglia
      in normal adult brain. We previously showed the up-regulated expression of KS in
      one of glioblastoma cell lines using anti-KS antibody (5D4). However, it has not
      been clarified whether KS is expressed in brain tumors and is involved in their
      malignancy. In this study, 54 astrocytic tumors were investigated about KS
      expression using Western-blot with 5D4. In six of 14 anaplastic astrocytomas
      (43%) and 23 of 34 glioblastomas (68%), KS was detected by 5D4. KS was hardly
      detected by 5D4 in diffuse astrocytoma, suggesting that KS-expression is
      significantly expressed in malignant astrocytic tumors. In immunohistochemistry,
      KS is highly expressed in cell surface of malignant astrocytic tumors. Taken
      together, KS might be associated with the malignancy of astrocytic tumors, and be
      useful for a prognostic factor of astrocytic tumors.

PMID- 18329384
TI  - Impairments of astrocytes are involved in the d-galactose-induced brain aging.
AB  - Astrocyte dysfunction is implicated in course of various age-related
      neurodegenerative diseases. Chronic injection of d-galactose can cause a
      progressive deterioration in learning and memory capacity and serve as an animal
      model of aging. To investigate the involvement of astrocytes in this model,
      oxidative stress biomarkers, biochemical and pathological changes of astrocytes
      were examined in the hippocampus of the rats with six weeks of d-galactose
      injection. d-galactose-injected rats displayed impaired antioxidant systems, an
      increase in nitric oxide levels, and a decrease in reduced glutathione levels.
      Consistently, western blotting and immunostaining of glial fibrillary acidic
      protein showed extensive activation of astrocytes. Double-immunofluorescent
      staining further showed activated astrocytes highly expressed inducible nitric
      oxide synthase. Electron microscopy demonstrated the degeneration of astrocytes,
      especially in the aggregated area of synapse and brain microvessels. These
      findings indicate that impairments of astrocytes are involved in oxidative stress
      induced brain aging by chronic injection of d-galactose.

PMID- 18329385
TI  - Indirect spectrophotometric determination of sodium ceftriaxone with n-propyl
      alcohol-ammonium sulfate-water system by extraction flotation of copper(II).
AB  - BACKGROUND: Although the determination methods of sodium ceftriaxone has been
      increasingly reported, these methods have their inherent limits preventing them
      from being broadly applied in common laboratories. In order to circumvent this
      problem, a rapid and simple method for the indirect spectrophotometric
      determination of sodium ceftriaxone is reported. METHOD: Sodium ceftriaxone was
      degraded completely in the presence of 0.20 mol/l sodium hydroxide in boiling
      water bath for 20 min. The thiol group (-SH) of the degradation product (I) of
      sodium ceftriaxone could reduce cupric to cuprous ions, and the resulting which
      was precipitated with the thiol group (-SH) of the degradation product (II) at pH
      4.0. By determining the residual amount of copper (II), the indirect
      determination of sodium ceftriaxone can be achieved. RESULT: Standard curve of
      sodium ceftriaxone versus the flotation yield of copper(II) showed that sodium
      ceftriaxone could be determined in low concentrations. The linear range of sodium
      ceftriaxone was 0.70-32 microg/ml and the detection limit evaluated by
      calibration curve (3sigma/k) was found to be 0.60 microg/ml. CONCLUSION: A simple
      and efficient method was developed and it has been successfully applied to the
      determination of sodium ceftriaxone in human serum and urine samples,
      respectively. It is expected that this method will find broad applications in the
      detection of cephalosporin derivatives with similar structure.

PMID- 18329386
TI  - Identification of operator sites within the upstream region of the putative mce2R
      gene from mycobacteria.
AB  - Mycobacterium tuberculosis harbors four mce operons. Among them, mce2 operon is
      preceded by a FadR-like regulator mce2R (Rv0586). Here, we report the operator
      sites of the mce2R and its orthologs in other sequenced mycobacteria and non
      mycobacterial species Nocardia farciana. All the identified DNA motifs illustrate
      the FadR subfamily specific nucleotide preference. Moreover, these motifs from
      the upstream region share sequence conservation, which is in agreement with the
      similarity of their DNA binding domain. Using electrophoretic mobility shift
      assay, we demonstrate that the predicted DNA motifs specifically interact with
      the recombinant Mce2R-Rv0586. Our present study has implications in the
      understanding of cis-regulatory elements and the auto-regulatory nature of the
      FadR subfamily of regulators.

PMID- 18329387
TI  - Localization of A20 to a lysosome-associated compartment and its role in NFkappaB
      signaling.
AB  - A20 is a tumor necrosis factor (TNF)-inducible zinc finger protein that contains
      both ubiquitinating and deubiquitinating activities. A20 negatively regulates
      NFkappaB (nuclear factor kappaB) signaling induced by TNF receptor family and
      Toll-like receptors, but the mechanism of A20 action is poorly defined. Here we
      show that a fraction of endogenous and ectopically expressed A20 is localized to
      an endocytic membrane compartment that is in association with the lysosome. The
      lysosomal association of A20 requires its carboxy terminal zinc finger domains,
      but is independent of its ubiquitin-modifying activities. Interestingly, A20
      mutants defective in membrane association also contain reduced NFkappaB
      inhibitory activity. These findings suggest the involvement of a lysosome
      associated mechanism in A20-dependent termination of NFkappaB signaling.

PMID- 18329388
TI  - Screening of senescence-associated genes with specific DNA array reveals the role
      of IGFBP-3 in premature senescence of human diploid fibroblasts.
AB  - Repeated exposures to sublethal concentrations of tert-butylhydroperoxide and
      ethanol trigger premature senescence of WI-38 human diploid fibroblasts. We found
      16 replicative senescence-related genes with similar alterations in expression
      level in replicative senescence and two models of stress-induced premature
      senescence. Among these genes was IGFBP-3. Using a siRNA approach, we showed that
      IGFBP-3 regulates the appearance of several biomarkers of senescence after
      repeated exposures of WI-38 fibroblasts to tert-butylhydroperoxide and ethanol.

PMID- 18329389
TI  - Identification of a plasmin-interactive site within the A2 domain of the factor
      VIII heavy chain.
AB  - Factor VIII is activated and inactivated by plasmin by limited proteolysis. In
      our one-stage clotting assay, these plasmin-catalyzed reactions were inhibited by
      the addition of isolated factor VIII A2 subunits and by Glu-Gly-Arg-active-site
      modified factor IXa. SDS-PAGE analysis showed that an anti-A2 monoclonal
      antibody, recognizing the factor IXa-interactive site (residues 484-509), blocked
      the plasmin-catalyzed cleavage at Arg(336) and Arg(372) but not at Arg(740).
      Surface plasmon resonance-based assays and ELISA demonstrated that the A2 subunit
      bound to active-site modified anhydro-plasmin with high affinity (K(d): 21 nM).
      Both an anti-A2 monoclonal antibody and a peptide comprising of A2 residues 479
      504 blocked A2 binding by approximately 80% and approximately 55%, respectively.
      Mutant A2 molecules where the basic residues in A2 were converted to alanine were
      evaluated for binding of anhydro-plasmin. Among the tested mutants, the R484A A2
      mutant possessed approximately 250-fold lower affinity than the wild-type A2. The
      affinities of K377A, K466A, and R471A mutants were decreased by 10-20-fold. The
      inhibitory effect of R484A mutant on plasmin-catalyzed inactivation of factor
      VIIIa was approximately 20% of that of wild-type A2. In addition, the
      inactivation rate by plasmin of factor VIIIa reconstituted with R484A mutant was
      approximately 3-fold lower than that with wild-type A2. These findings
      demonstrate that Arg(484) plays a key role within the A2 plasmin-binding site,
      responsible for plasmin-catalyzed factor VIII(a) inactivation.

PMID- 18329390
TI  - Narrative text analysis of Kentucky tractor fatality reports.
AB  - Narrative information in fatality investigation reports contains data elements
      not routinely analyzed with coded occupational injury surveillance data. A
      narrative text analysis of 69 Kentucky Fatality Assessment and Control Evaluation
      (FACE) agricultural tractor fatality reports from 1994 to 2004 was performed. The
      FACE reports were developed using the National Institute for Occupational Safety
      and Health, Division of Safety Research-recommended FACE report format that
      incorporates Haddon's matrix. Haddon's matrix separates the fatal incident into
      three event phases and is used to develop points of intervention based on human,
      organizational, and environmental factors. A multivariate logistic regression
      analysis for association between identified exposure variables and the outcomes
      of interest was undertaken. The operation of a tractor with an attached bucket,
      muddy terrain, and being thrown from the tractor were independent risk factors
      for being declared "dead at the scene". A tractor rollover and operation of a
      tractor on a slope were independent risk factors for being "crushed" by a
      tractor. Narrative text analysis of FACE fatality investigation reports is a
      valuable tool for the identification of additional factors contributing to
      tractor fatalities that can inform farm safety training, identify new areas for
      agricultural interventions, and support the development of new agricultural
      engineering strategies.

PMID- 18329391
TI  - Routes to failure: analysis of 41 civil aviation accidents from the Republic of
      China using the human factors analysis and classification system.
AB  - The human factors analysis and classification system (HFACS) is based upon
      Reason's organizational model of human error. HFACS was developed as an
      analytical framework for the investigation of the role of human error in aviation
      accidents, however, there is little empirical work formally describing the
      relationship between the components in the model. This research analyses 41 civil
      aviation accidents occurring to aircraft registered in the Republic of China
      (ROC) between 1999 and 2006 using the HFACS framework. The results show
      statistically significant relationships between errors at the operational level
      and organizational inadequacies at both the immediately adjacent level
      (preconditions for unsafe acts) and higher levels in the organization (unsafe
      supervision and organizational influences). The pattern of the 'routes to
      failure' observed in the data from this analysis of civil aircraft accidents show
      great similarities to that observed in the analysis of military accidents. This
      research lends further support to Reason's model that suggests that active
      failures are promoted by latent conditions in the organization. Statistical
      relationships linking fallible decisions in upper management levels were found to
      directly affect supervisory practices, thereby creating the psychological
      preconditions for unsafe acts and hence indirectly impairing the performance of
      pilots, ultimately leading to accidents.

PMID- 18329392
TI  - Developing a driving Safety Index using a Delphi stated preference experiment.
AB  - Whilst empirical evidence is available concerning the effect of some aspects of
      driving behaviour on safety (e.g. speed choice), there is scant knowledge about
      safety thresholds, i.e. the point at which behaviour can be considered unsafe.
      Furthermore, it is almost impossible to ascertain the interaction between various
      aspects of driving behaviour. For example, how might drivers' lateral control of
      a vehicle be mediated by their speed choice-are the effects additive or do they
      cancel each other out. Complex experimental or observational studies would need
      to be undertaken to establish the nature of such effects. As an alternative, a
      Delphi study was undertaken to use expert judgement as a way of deriving a first
      approximation of these threshold and combinatory effects. Using a stated
      preference technique, road safety professionals make judgements about drivers'
      safe or unsafe behaviour. The aim was to understand the relative weightings that
      are assigned to a number of driver behaviours and thereby to construct a Safety
      Index. As expected, experts were able to establish thresholds, above (or below)
      which changes to the behavioural parameters had minimal impact on safety. This
      provided us with a Safety Index, based on a model that had face validity and a
      convincing range of values. However, the experts found the task of combining
      these driver behaviours more difficult, reflecting the elusive nature of safety
      estimates. Suggestions for future validation of our Safety Index are provided.

PMID- 18329393
TI  - Mixed logit analysis of safety-belt use in single- and multi-occupant vehicles.
AB  - In this paper we demonstrate a modeling approach that can be used to better
      understand the use of safety belts in single- and multi-occupant vehicles, and
      the effect that vehicle, roadway and occupant characteristics have on usage
      rates. Using data from a roadside observational survey of safety-belt use in
      Indiana, a mixed (random parameters) logit model is estimated. Potentially
      interrelated choices of safety-belt use by drivers and front-seat passengers are
      examined. The approach we use also allows for the possibility that estimated
      model parameters can vary randomly across vehicle occupants to account for
      unobserved effects potentially relating to roadway characteristics, vehicle
      attributes, and driver behavior. Estimation findings indicate that the choices of
      safety-belt use involve a complex interaction of factors and that the effect of
      these factors can vary significantly across the population. Our results show that
      the mixed logit model can provide a much fuller understanding of the interaction
      of the numerous variables which correlate with safety-belt use than traditional
      discrete-outcome modeling approaches.

PMID- 18329394
TI  - Assessment of driving after stroke--a pluridisciplinary task.
AB  - The aim of the study was to analyze the assessment procedure and identify
      predictors for the team decision when assessing fitness to drive a car after
      stroke. The material used was a retrospective data set with 200 stroke clients
      from Queen Elisabeth's Foundation Mobility Centre at Banstead UK. Fifty-four
      percent of clients were considered fit to continue driving where 9% could resume
      driving after car adaptation and training. Important factors for the outcome were
      vision (acuity and field), neuropsychological functions (divided attention), and
      track and/or on road test (reaction time, anticipation, speed, and positioning).
      Cognitive impairment was the main problem in those who failed the driving test
      and judged not fit for continued driving. Car adaptation, mainly comprising
      infrared transmitted secondary controls together with automatic transmission was
      recommended in 35% of the cases. CONCLUSIONS: The contribution of different
      specialist groups appears to be necessary for an effective evaluation, but the
      assessment procedure can be done more cost-effectively by dividing it into two
      separate parts and removing certain subtests. The in-car track test is an
      important part of the assessment procedure with a high face validity and could in
      many cases make it unnecessary to perform in-traffic tests with unsafe drivers.
      Car adaptation is often necessary for a client with pronounced hemi-paresis and a
      full road test can for those only be performed after training the use of car
      controls.

PMID- 18329395
TI  - Statistical analysis of "looked-but-failed-to-see" accidents: highlighting the
      involvement of two distinct mechanisms.
AB  - Circumstances where "looked-but-failed-to-see" accidents arise are a particular
      subject of study. In order to better understand why normal drivers could miss a
      relevant event signaling danger, more than 500 accidents were analyzed in-depth
      with regard to driver-environment-goal interactions. Results show four typical
      situations that imply two distinct mechanisms. When a failure arose at the
      perceptual stage, drivers actually never saw the danger while they were going
      straight at a junction or turning left to park their car. When failure arose at
      the processing stage, there was evidence that drivers saw the danger even when
      their recall of it was lacking. In fact, drivers saw the danger too late to avoid
      collision when they were overtaking another road user or trying to find his/her
      way. These are called "looked-but-failed-to-see-accidents". Accident patterns are
      discussed according to driver's goal involvement and local setting to suggest
      directions for further investigation with a special emphasis on change blindness.

PMID- 18329396
TI  - Why Turks do not use seat belts? An interview study.
AB  - Despite the effectiveness of seat belt use and legislation, seat belt use rate is
      low in Turkey. The aim of this study was to investigate the motives to use and
      not to use a seat belt in different traveling conditions in a sample of car
      drivers and passengers. Interviews were made face to face with 221 interviewees
      from different age and occupation groups. Frequently reported reasons for using a
      seat belt were traveling conditions, safety, situational conditions, habit of
      using a seat belt, and avoiding punishment. Frequently reported reasons for not
      using a seat belt were situational conditions, not believing in the
      effectiveness, discomfort and having no habit. Safety was the strongest predictor
      of reported seat belt use in both low and high risk traveling conditions.
      Findings suggest that seat belt campaigns should mainly emphasize seat belt's
      safety impact and aim at habit formation.

PMID- 18329397
TI  - Exploring motorcyclist injury severity in approach-turn collisions at T
      junctions: focusing on the effects of driver's failure to yield and junction
      control measures.
AB  - Research has suggested that motorcyclists involved in approach-turn crashes were
      much more injurious than any other crash-type. This paper investigates the
      determinants of motorcyclist injury severity resulting from such crash types that
      occurred at T-junctions, with emphasis on the effects of driver's failure to give
      way and various junction control measures. The ordered probit models of
      motorcyclist injury severity were estimated using the data extracted from the
      STATS19 accident injury database (1991-2004). Approach-turn collisions are
      categorised into two sub-crashes based on the manoeuvres motorcycles and vehicles
      were making prior to the collisions. The modelling results uncover several
      important determinants of injury severity: for example, injuries appeared to be
      greatest when an approaching motorcycle collided with a turning-right vehicle,
      and such effect was found to exacerbate injury severity when stop, give-way signs
      and markings controlled the junction. A turning-right driver that was identified
      to fail to yield to an approaching motorcyclist was also found to severely injure
      the motorcyclist. The findings of this study may offer guidelines for further
      research and provide some important preliminary evidence for the development of
      countermeasures that may help prevent the specific hazards from occurring.

PMID- 18329398
TI  - Thoracic and lumbar spinal impact tolerance.
AB  - INTRODUCTION: Thoracolumbar injuries resulting from motor vehicle accidents,
      falls, and assaults have a high risk of morbidity and mortality. However, there
      are no biomechanically based standards that address this problem. METHODS: This
      study used four cadaveric porcine specimens as a model for direct spinal impact
      injuries to humans to determine an appropriate injury tolerance value. The
      anthropometric parameters of these specimens are compared with values found in a
      large human cadaveric dataset. Each specimen was subjected to five impacts on the
      dorsal surface of the lower thorax and abdomen. RESULTS: The injuries ranged from
      mild spinous process fractures to endplate fractures with anterior longitudinal
      ligament (ALL) transactions with a maximum AIS=3. The average peak reaction force
      for the thoracic failure tests was 4720+/-1340 N, and the average peak reaction
      force for the lumbar failure tests was 4650+/-1590 N. DISCUSSION: When scaled to
      human values using anthropometric parameters determined in this study, the force
      at which there is a 50% risk of injury is 10,200+/-3900 N. This value favorably
      compares to that found in the existing literature on isolated vertebral segments.
      SUMMARY: After demonstrating that the porcine model can be used as a spinal
      impact model for the human, the resulting injury risk value can be used in
      determining new standards for human injury risk or in guiding the design of
      safety equipment for the back.

PMID- 18329399
TI  - Alcohol consumption among recreational boaters: factors for intervention.
AB  - Recreational boating is a popular leisure time activity in many countries. It is
      estimated that, in Australia, boating incidents cause more harm than rail and air
      crashes combined and, in terms of transport, are second only to motor vehicle
      crashes as a cause of serious injury. The consumption of alcohol among
      recreational boaters is considered an important risk factor for fatalities and
      injuries among both operators and passengers. Using a database of all
      recreational vessels registered in Western Australia (WA), a sample of 500 adult
      boaters was recruited to participate in a telephone survey. The effects of
      demographic variables and boating characteristics upon the use of alcohol among
      recreational boaters on their last trip were explored using logistic regression.
      The odds of not having a drink were associated, after adjusting for age, with
      having completed a boating education course and with carrying children less than
      12 years on board. The use of alcohol was not found to be prevalent among WA
      recreational boat owners. Based on these findings, it is recommended that efforts
      to decrease boating-related incidents, such as through education and legislation
      measures, be monitored over time to determine the effects of these strategies
      upon safety behaviours.

PMID- 18329400
TI  - Quantile regression provides a fuller analysis of speed data.
AB  - Considerable interest already exists in terms of assessing percentiles of speed
      distributions, for example monitoring the 85th percentile speed is a common
      feature of the investigation of many road safety interventions. However, unlike
      the mean, where t-tests and ANOVA can be used to provide evidence of a
      statistically significant change, inference on these percentiles is much less
      common. This paper examines the potential role of quantile regression for
      modelling the 85th percentile, or any other quantile. Given that crash risk may
      increase disproportionately with increasing relative speed, it may be argued
      these quantiles are of more interest than the conditional mean. In common with
      the more usual linear regression, quantile regression admits a simple test as to
      whether the 85th percentile speed has changed following an intervention in an
      analogous way to using the t-test to determine if the mean speed has changed by
      considering the significance of parameters fitted to a design matrix. Having
      briefly outlined the technique and briefly examined an application with a widely
      published dataset concerning speed measurements taken around the introduction of
      signs in Cambridgeshire, this paper will demonstrate the potential for quantile
      regression modelling by examining recent data from Northamptonshire collected in
      conjunction with a "community speed watch" programme. Freely available software
      is used to fit these models and it is hoped that the potential benefits of using
      quantile regression methods when examining and analysing speed data are
      demonstrated.

PMID- 18329401
TI  - Initial age of unlicensed motorcycling experience for a cohort of high school
      students.
AB  - The aim of this study is to use retrospective data to examine the initial age of
      unlicensed motorcycling experience for a cohort of senior high school students in
      Taiwan. The life-table method was applied to estimate the probability of
      unlicensed motorcycling at different age intervals below the minimum licensing
      age. The results indicated that an increase in the prevalence of unlicensed
      teenage motorcycling began at 10 years of age and peaked in the ages between 16
      and 17 years. Only 38% of students had no motorcycle riding experience when they
      reached the minimum licensing age of 18 years. Gender and parental attitude were
      the factors that had a significant influence on the initial motorcycling age. In
      addition, we observed a significant difference between licensed and unlicensed
      students in the following areas: parental attitude, proportion of students using
      borrowed motorcycles, and riding and accident frequency. The results reveal a
      number of important implications, such as the promotion of alternative modes of
      transport, increased parental monitoring, and penalty enhancement, that may help
      to suppress the tendency of teenagers' unlicensed motorcycling.

PMID- 18329402
TI  - The effects of roundabouts on traffic safety for bicyclists: an observational
      study.
AB  - A before-and-after study was carried out of injury accidents involving bicyclists
      on 91 roundabouts in Flanders-Belgium. The study design accounted for the effects
      of general safety trends and regression-to-the-mean, but could not take into
      account the possibility of specific changes in traffic volume at roundabouts. The
      conversion of intersections into roundabouts produces a significant 27% increase
      in the number of injury accidents involving bicyclists on or nearby the
      roundabouts. The increase is even higher for accidents involving fatal or serious
      injuries (41-46%). Compared to the proven favourable effects of roundabouts on
      safety in general, this result is unexpectedly poor. However, the effects of
      roundabouts on bicycle accidents differ depending on whether these roundabouts
      are built inside or outside built-up areas. When inside built-up areas, the
      construction of roundabouts increased the number of injury accidents involving
      bicyclists by 48%. For accidents causing fatal or serious injuries inside built
      up areas, an average increase of 77% was found. However, outside built-up areas
      the zero-hypothesis of 'no safety effect for bicyclists' cannot be rejected (best
      estimate: +1% accidents, not significant). Roundabouts that replace traffic
      signals perform worse when compared to roundabouts at other types of
      intersections.

PMID- 18329403
TI  - Escalator-related injuries among older adults in the United States, 1991-2005.
AB  - This study describes the epidemiology of escalator-related injuries among adults
      age 65 and older in the U.S. between 1991 and 2005, through a retrospective
      analysis of data from the National Electronic Injury Surveillance System of the
      U.S. Consumer Product Safety Commission. There were an estimated 39,850 escalator
      related injuries and no fatalities. The overall injury rate was 7.8/100,000
      population. During the study period 1991-2005, the rate of escalator-related
      injuries doubled. The mean age of the study population was 80.1 years (S.D.=8.5
      years) with 73.3% female. The most frequent cause of injury was a slip, trip or
      fall (84.9%, 95% CI: 82.7-87.2%). The most frequently injured body parts were the
      lower extremities (25.9%, 95% CI: 21.5-30.2%) and the head (25.0%, 95% CI: 20.5
      29.5%). The leading type of injury was soft tissue injuries (54.2%, 95% CI: 49.7
      58.7%) followed by lacerations (22.3%, 95% CI: 18.4-26.1%) and fractures (15.6%,
      95% CI: 13.1-18.1%). The rate of head injuries and the rate of hospitalizations
      increased with age. Escalator-related injuries occur infrequently but may result
      in significant trauma. These injuries are often associated with a slip, trip or
      fall. Awareness of the risks and the circumstances leading to escalator injuries
      allows for better direction of intervention strategies on the part of injury
      prevention specialists.

PMID- 18329404
TI  - High re-arrest rates among drug-impaired drivers despite zero-tolerance
      legislation.
AB  - BACKGROUND: A zero-tolerance law for driving under the influence of drugs (DUID)
      in Sweden led to a 10-fold increase in the number of cases submitted by the
      police for toxicological analysis. The statutory blood-alcohol concentration
      (BAC) limit for driving is 0.2 mg/g ( approximately 0.02 g%). METHODS: An in
      house database (TOXBASE) was used to investigate re-arrests for impaired driving
      over 4 years (2001-2004), which comprised 36,799 cases. The age, gender, re
      arrest rate of the offenders and the concentrations of ethanol and amphetamine in
      blood samples were evaluated. RESULTS: We found that 44% of individuals
      (N=16,277) re-offended 3.2 times on average (range 1-23 arrests). Between 85 and
      89% of first-time offenders were men and there was also a male dominance among
      the recidivists (88-93%). The mean age of drunken drivers was approximately 40
      years compared with approximately 35 years for driving under the influence of
      amphetamine, which was the drug identified in 50-60% of DUID cases, either alone
      or together with other licit or illicit drugs. The median BAC was 1.5mg/g (
      approximately 0.15 g%), which suggests a dominance of heavy drinkers. The median
      BAC was even higher in recidivists (1.6-1.7 mg/g). The median concentration of
      amphetamine in blood was 1.0 mg/L in recidivists compared with 0.5mg/L in the
      first-time offenders. About 14% of drunken drivers re-offended 1-10 times
      compared with 68% of DUID suspects, who were re-arrested 1-23 times. People with
      only a scheduled prescription drug in blood were re-arrested much less frequently
      ( approximately 17%) compared with those taking illicit drugs (68%). CONCLUSIONS:
      The appreciable increase in number of arrests for DUID after a zero-tolerance law
      might reflect a heightened enthusiasm by the police authorities armed with
      knowledge that a prosecution is easier to obtain. Zero-tolerance laws do not
      deter people from impaired driving judging by the high re-arrest rates. During
      the sentencing of hardcore offenders, the courts should give more consideration
      to the underlying substance abuse problem.

PMID- 18329405
TI  - Relationships between young drivers' personality characteristics, risk
      perceptions, and driving behaviour.
AB  - Research has shown that inexperienced drivers underestimate the risks associated
      with a range of driving situations. In addition, personality factors are an
      important influence on both risk perceptions and driving behaviour. The study
      investigated the strength of relationship between personality factors, risk
      perceptions, and driving behaviour among young, mainly inexperienced drivers. One
      hundred and fifty-nine students aged between 17 and 20 completed an online
      questionnaire assessing five facets of personality, four components of risk
      perceptions, and one measure of driving behaviour. Using structural equation
      modeling as a means of assessing the overall fit of each model, 39% of the
      variance in young drivers' speeding was accounted for by Excitement-Seeking,
      Altruism, their Aversion to Risk Taking, and their own likelihood of having an
      accident, with Altruism and Aversion to Risk Taking both showing moderate
      negative relationships. Road safety interventions should examine whether they
      strengthen young drivers' appreciation of the impact of their actions on others
      through positive reinforcement of altruistic norms.

PMID- 18329406
TI  - Comparison of roadside crash injury metrics using event data recorders.
AB  - The occupant impact velocity (OIV) and acceleration severity index (ASI) are
      competing measures of crash severity used to assess occupant injury risk in full
      scale crash tests involving roadside safety hardware, e.g. guardrail. Delta-V, or
      the maximum change in vehicle velocity, is the traditional metric of crash
      severity for real world crashes. This study compares the ability of the OIV, ASI,
      and delta-V to discriminate between serious and non-serious occupant injury in
      real world frontal collisions. Vehicle kinematics data from event data recorders
      (EDRs) were matched with detailed occupant injury information for 180 real world
      crashes. Cumulative probability of injury risk curves were generated using binary
      logistic regression for belted and unbelted data subsets. By comparing the
      available fit statistics and performing a separate ROC curve analysis, the more
      computationally intensive OIV and ASI were found to offer no significant
      predictive advantage over the simpler delta-V.

PMID- 18329407
TI  - A comparison of self-reported motor vehicle collision injuries compared with
      official collision data: an analysis of age and sex trends using the Canadian
      National Population Health Survey and Transport Canada data.
AB  - OBJECTIVE: The purpose of this study was to compare the age and sex trends of
      motor vehicle collision injuries between a nationally representative self-report
      survey and official police motor vehicle collision report data. To do this,
      population-based estimates of motor vehicle collision injuries were established
      using data from the National Population Health Survey (NPHS), a prospective,
      population-based, longitudinal survey that was compared to Transport Canada's
      official motor vehicle collision report statistics. METHODS: Aggregated mean data
      (1994-1996) were compared for seven age groups (15-19, 20-24, 25-34, 35-44, 45
      54, 55-64, and 65+) from both data sets. RESULTS: No significant differences were
      found between males' and females' MVC injuries for any age category in the NPHS.
      A comparison of the NPHS and Transport Canada data found two small (significant)
      within-sex differences between the data sets, but overall, the analysis largely
      revealed similar trends for self-reported injury for all age categories and sex.
      CONCLUSIONS: The results indicate that the incidence of injuries based on self
      report data in a nationally representative sample is similar to official sources
      of reporting and are thus a valid indicator or motor vehicle collision injury
      incidence. The results also confirm that injury trends differ from fatality
      trends.

PMID- 18329408
TI  - Differences of drivers' reaction times according to age and mental workload.
AB  - This study was designed to examine differences in reaction times of drivers of
      various age groups and to assess the influence of mental workload on reaction
      times. Experiments were performed on a simulated street and under other
      conditions to identify drivers with long reaction times and drivers whose
      reaction times are affected strongly by mental workloads while driving on a
      public road. Reaction times after hearing a buzzer were measured under five
      conditions: (1) sitting in a stationary vehicle, (2) executing mental
      calculations in a stationary vehicle, (3) driving on a simulated street, (4)
      executing mental calculations while driving on a simulated street, and (5)
      driving on a public road. Subjects were 10 drivers each of three age groups. Each
      experiment was performed by these subjects under the five conditions. Results
      showed that mental calculations increased the average reaction time for each age
      group. Mental calculations increased differences among age groups and
      individuals, and increased differences in respective drivers' individual
      performance. Mental calculations influenced elderly drivers' reaction times
      remarkably. Results also demonstrated that an experiment on a simulated street
      identified drivers who showed long reaction times on a public road.

PMID- 18329409
TI  - Identifying social mechanisms for the prevention of adolescent drinking and
      driving.
AB  - This study identifies social mechanisms that might help prevent youth from being
      involved in driving under the influence of alcohol (DUI) and riding with drinking
      drivers (RWDD). Data collected through telephone surveys with 1534 adolescents
      and young adults aged 15-20 years (mean=17.6, S.D.=1.6) in California, USA, were
      analyzed. Structural equation modeling analyses showed that DUI and RWDD were
      strongly related to drinking in unstructured situations, modeling of DUI by peers
      and parents, and perceived peer approval or disapproval of DUI. DUI outcome
      expectancies were indirectly related to DUI and RWDD through situational
      drinking. Parental monitoring and DUI law enforcement were also indirectly
      related to DUI and RWDD through DUI expectancies and other mechanisms. The
      findings, overall, suggest that parental influence remains important even through
      late adolescence. Parental monitoring, in particular, might help to reduce
      unstructured socializing with peers, drinking, and affiliation with peers who
      engage in DUI. Parental monitoring may also foster beliefs about the risks of
      DUI. Conversely, parents' own DUI behavior may normalize drinking and DUI
      behaviors, thus countering monitoring efforts.

PMID- 18329410
TI  - Magnitude and categories of pedestrian fatalities in South Africa.
AB  - Road traffic injuries, a major global public health burden, are concentrated in
      low-income and middle-income countries.(1) In contrast to high-income countries,
      pedestrians make up the largest group of road traffic injuries and fatalities in
      low- and middle-income countries. This article presents an analysis of pedestrian
      fatalities (2001-2004) in four South African cities. The article describes the
      magnitude, demographic, and temporal factors associated with pedestrian
      fatalities and presents a typological analysis to identify particular groups of
      at risk pedestrians. The analysis can serve to inform the development of
      prevention programmes tailored to the needs of specific at risk pedestrian
      groups. Data were obtained from the National Injury Mortality Surveillance System
      (NIMSS). The results indicated that there were a total of 7433 pedestrian deaths
      (2001-2004) for the four cities and the majority occurred over weekends. Most
      (56.7%) were between ages 20 and 44 years. Overall, there were 3.3 male
      pedestrian deaths for every female pedestrian death, and over half (58%) of the
      4004 cases tested were positive for alcohol. A typological analysis identified
      three categories of pedestrian fatalities: (1) male pedestrian fatalities that
      showed high levels of alcohol concentrations, (2) female and elderly pedestrian
      deaths that occurred between 6 AM and midday, and (3) children, adolescents, and
      young adult pedestrian fatalities that typically occurred during weekday
      afternoons and evenings. The findings call for multiple strategies for combating
      pedestrian fatalities.

PMID- 18329411
TI  - The effects of safety climate on vessel accidents in the container shipping
      context.
AB  - This study empirically evaluates the influence of safety climate on vessel
      accidents from a seafarer's perspective, specifically in the container shipping
      context. Factor analysis revealed six safety climate dimensions: management
      safety practices, supervisor safety practices, safety attitude, safety training,
      job safety, and co-workers' safety practices. Logistic regression analysis was
      used to evaluate the effects of safety climate dimensions on vessel accidents in
      respect of crew fatality and vessel failure. Study findings indicated that
      management safety practices, safety training, and job safety dimensions
      significantly affect crew fatality incidence, and the job safety dimension has a
      significant influence on vessel failure. Overall, results suggest the job safety
      dimension has the most important effect on vessel accidents, followed by
      management safety practices and safety training dimensions. Theoretical and
      practical implications of the findings for vessel accident prevention in the
      container shipping context are discussed.

PMID- 18329412
TI  - Daytime driving simulation performance and sleepiness in obstructive sleep apnoea
      patients.
AB  - BACKGROUND: Sleepiness related car accidents are common in obstructive sleep
      apnoea syndrome (OSAS) patients. The objective measurements of sleepiness used in
      clinical setting quantify the tendency to fall asleep in quiet situations that
      are completely different from driving. METHODS: We studied 30 OSAS patients with
      subjective (subjective sleepiness scales) and objective (multiple sleep latency
      test, MSLT) sleepiness measurements, associated with driving simulation test
      (DST), previously validated in young healthy subjects. The results of subjective
      and objective sleepiness tests were compared with simulated driving performance
      in order to evaluate the suitability of our DST for measuring alertness. RESULTS:
      Subjective and objective sleepiness measurements were significantly correlated
      with driving performance on the simulator. The most significant correlates of
      sleepiness were the measures of the primary vehicle control task on the
      simulator: lane position variability and crash data. The comparison of DST and
      MSLT results suggested our driving simulated approach could be used to evaluate
      daytime sleepiness in the clinical setting of OSAS patients. CONCLUSIONS: Our DST
      is a suitable objective tool to detect sleepiness in OSAS patients, and could be
      useful in the clinical setting of sleep medicine and research.

PMID- 18329413
TI  - The influence of body mass index on thoracic injuries in frontal impacts.
AB  - For this study, a comprehensive analysis was performed to assess the influence of
      body mass index on thoracic injury potential. The data for this study were
      obtained from the National Automotive Sampling System-Crashworthiness Data System
      (NASS-CDS) database for years 1993-2005. Obese occupants had a 26 and 33% higher
      risk of AIS > or = 2 and AIS > or = 3 thoracic injury when compared to lean
      occupants. The increased risk of AIS > or = 3 injury due to obesity was slightly
      higher for older occupants, but the influence of age was greater than that of
      obesity. The increase in injury potential was higher for unbelted obese occupants
      than unbelted. Non-parametric and parametric risk curves were developed to
      estimate the risk of thoracic injury based on occupant BMI, belt use and delta-V.
      Overall, increase in thoracic injury risk due to obesity is more prominent in
      males and older occupants and for occupants sustaining AIS > or = 3 thoracic
      injuries.

PMID- 18329414
TI  - An implicit non-self-report measure of attitudes to speeding: development and
      validation.
AB  - Speeding is a major contributor to road trauma and attitudes toward speeding are
      hypothesised to be a key determinant of the behaviour. Attitudinal research is
      limited by reliance on self-report measures and the attendant possibility of
      reporting biases. The Implicit Association Test (IAT) aims to measure attitudes
      without reliance on self-report, by assessing the association between a target
      concept and an evaluation, in terms of reaction time for compatible versus non
      compatible pairings. The present research aimed to develop and evaluate an IAT to
      measure attitudes to speeding. Forty-five licensed drivers completed the speed
      related IAT, and drove a driving simulator. Participants also completed a
      questionnaire that assessed self-reported attitudes to speeding, and several
      variables theoretically related to attitudes, including speeding behaviour.
      Observed IAT results suggested that attitudes toward speeding are negative, and
      were generally consistent with results derived from the simulated driving and
      self-reported behaviours, beliefs, and attitudes. Thus, the speed-related IAT
      appears to be a valid measure of attitudes toward speeding, which might be used
      to measure attitudes in road safety research without reliance on self-report.

PMID- 18329415
TI  - Testing assumptions implicit in the use of the 15-second rule as an early
      predictor of whether an in-vehicle device produces unacceptable levels of
      distraction.
AB  - Given the proliferation of in-vehicle technologies, techniques must be developed
      to ensure devices do not produce unacceptable levels of distraction. One approach
      is to use static time on task (e.g., the 15-second rule). However, this practice
      makes three critical assumptions: (1) static time on task predicts time on task
      while driving; (2) time on task measured in a hazard-free environment predicts
      time on task when drivers expect hazards; (3) time on task predicts perceived
      distraction, collisions, and driving errors. To test these assumptions, two tasks
      were compared in 32 drivers using a driving simulator. The tasks were
      manipulating controls of a radio/tape deck and dialling a hand-held cellular
      phone. Static time on task underestimated dynamic time on task, though the
      differences between tasks were roughly consistent across testing conditions, with
      the cellular task taking more time. Participants who expected hazards required
      slightly more time on task than those who did not, but the effect was only
      marginal (p=0.09) and consistent across tasks. Finally, the device with higher
      static time on task also produced significantly more lane deviations and
      perceived interference, though the predicted pattern of results did not emerge
      for collisions and hazard response time.

PMID- 18329416
TI  - An assessment of the relevance of laboratory and motorcycling tests for
      investigating time of day and sleep deprivation influences on motorcycling
      performance.
AB  - The aim of this study was to assess time of day and sleep deprivation impacts on
      motorcycling performance taking into consideration key variables, such as
      reaction time, motor coordination and vigilance that are principally involved in
      a riding task. Eight subjects participated in different tests sessions planned at
      06:00 and 18:00h after a normal night's sleep and after a night of total sleep
      deprivation. During each session all subjects completed "laboratory" and
      "motorcycling" tests that were designed to assess each of the variables tested.
      As classically observed in sport performance, motorcycling performance
      demonstrates a time of day fluctuation by increasing from 06:00 to 18:00h during
      the day after a normal night's sleep. For each variable tested, the effects of
      sleep deprivation depend on the design of the test conditions. Thus, the data
      collected in laboratory specific conditions are more affected than those noted in
      arranged motorcycling situations. Taking into account that the sample size used
      in this study was limited, which may limit the results interpretations, these
      discrepancies suggest that during complex tasks, compensation mechanisms may be
      set up between different resources so as to maintain a good level of performance.

PMID- 18329417
TI  - Modeling safe and unsafe driving behaviour.
AB  - A sample of 743 Dutch drivers was queried about driving-related errors and
      violations, and about the frequency of their accident involvement over the past 3
      years. In addition, the following risky behaviours and characteristics related to
      driving were measured through self-report: strategic decisions made about driving
      before starting a trip, attitudes related to committing violations, psychological
      precursors of unsafe driving (such as being tired or stressed when driving), and
      physical precursors of unsafe driving (suffering physical or psychological
      handicaps when driving). The results show that several scales have acceptable
      reliability coefficients, though several others are in need of improvement. Path
      analysis showed that an acceptable structural model could be developed to
      describe all empirical relationships. Considerable parts of the variance in the
      violations scores and the psychological precursors scores could be explained by
      the other model variables. In terms of predictive power, "unsafe" attitudes,
      physical precursors, and psychological precursors had the most impact, each
      explaining up to 9% of the variance in violations scores, errors scores, and/or
      psychological precursors scores. The way these results can be utilized in future
      accident prevention programs and in driver training programs are indicated, as
      are their implications for future research.

PMID- 18329418
TI  - Factors associated with the premature graduation of children into seatbelts.
AB  - This study investigated the factors associated with the premature graduation into
      seatbelts for Australian children aged 4-11 years. From 699 child restraint use
      questionnaires, 195 children were identified as meeting the booster seat height
      weight criteria (height: 100-145 cm and weight: 14-26 kg). Of these children, 44%
      were correctly traveling in a booster seat, while 56% had been moved prematurely
      into a seatbelt. A multivariable logistic regression model showed that there were
      a number of key predictors associated with the premature graduation to seatbelts.
      For example, children who were moved prematurely into a seatbelt were more likely
      to be older, have other children travelling in the vehicle and have younger
      parents compared to children appropriately restrained in a booster seat. In
      addition, there was a significant interaction between vehicle type and parent's
      household income. Based on the findings of this study, a number of
      recommendations are made for strategies to enhance appropriate restraint use for
      this age group, as well as for future research.

PMID- 18329419
TI  - Stereotype threat increases the likelihood that female drivers in a simulator run
      over jaywalkers.
AB  - Stereotype threat, or the belief that one may be the target of demeaning
      stereotypes, leads to performance disruptions in a variety of domains. Two
      experiments conducted in a driving simulator demonstrate that stereotype threat
      also disrupts control of an automobile. Women who were reminded of the stereotype
      that females are poor drivers were more than twice as likely to collide with
      jaywalking pedestrians than women who were not reminded of this stereotype.
      Experiment 2 also revealed that the magnitude of this effect was equivalent to
      that produced by a secondary task, suggesting that stereotype threat might
      diminish driving performance via a disruptive mental load.

PMID- 18329420
TI  - Assessing the awareness of performance decrements in distracted drivers.
AB  - Many studies have documented the performance decrements associated with driver
      distractions; however, few have examined drivers' awareness of these distraction
      effects. The current study measured how well-calibrated drivers are with respect
      to performance decrements from distracting tasks. In this test track study, 40
      younger and older drivers completed a series of tasks on a hand-held or hands
      free cell phone while driving around a course in an instrumented vehicle.
      Subjective estimates of performance decrements were compared to actual
      performance decrements. Although their driving performance suffered in dual-task
      conditions, drivers were generally not well-calibrated to the magnitude of the
      distraction effects (r=-.38 to .16). In some cases, estimates of distraction were
      opposite of the observed effects (i.e., smaller estimates of distraction
      corresponded to larger performance deficits). Errors in calibration were
      unassociated with several measures of overconfidence in safety and skill, among
      other variables. We discuss the implications of these findings for potential
      mitigation strategies for distracted driving.

PMID- 18329421
TI  - Lane change behavior with a side blind zone alert system.
AB  - This in-traffic study explored the effect of a side blind zone alert (SBZA)
      system on driver lane change behavior. Such a system may help drivers avoid lane
      change crashes by warning them with a side mirror display when a vehicle is
      detected in their blind zone. Participants drove with and without the SBZA system
      enabled, and were instructed to evaluate vehicle ride characteristics and only
      given an "incidental" system explanation. Overall, drivers failed to execute
      "over the shoulder" (blind zone) glances for 68 and 85% of the left and right
      lane changes, respectively. This suggests that the SBZA display provides
      information to the driver that often fails to be obtained via over the shoulder
      glances. In addition, when the SBZA system was enabled there was a 31% reduction
      in left lane changes attempted without the driver checking the left mirror, and a
      23% reduction in right lane changes attempted without the driver checking the
      inside mirror. These results, coupled with the assumption that "did not see other
      vehicle" is a principal causal factor in many lane change crashes, suggests that
      the SBZA system may assist drivers in avoiding lane change crashes.

PMID- 18329422
TI  - Capturing attention to brake lamps.
AB  - Rear-end collisions and distraction are major concerns and basic research in
      cognitive psychology concerning attention in visual search is applicable to these
      problems. It is proposed that using yellow tail lamps will result in faster
      reaction times and fewer errors than current tail lamp coloring (red) in
      detecting brake lamps (red) in a "worst case" scenario where brake lamp onset,
      lamp intensity and temporal and contextual cues are not available. Participants
      engaged in a visual search for brake lamps in two conditions, one using red tail
      lamps with red brake lamps and one with the proposed combination of yellow tail
      lamps with red brake lamps in which they indicated by keyboard response the
      presence or absence of braking cars. The hypothesis that separating brake and
      tail lamps by color alone would produce faster RTs, reduce errors, and provide
      greater conspicuity was supported. Drivers and non-drivers detect absence and
      presence of red brake lamps faster and with greater accuracy with the proposed
      yellow tail lamps than red tail lamps without the aid of any of the
      aforementioned cues. Vehicle conspicuity will be improved and reductions in rear
      end collisions and other accidents will be reduced by implementing the proposed
      yellow tail lamp coloring.

PMID- 18329423
TI  - Risk perception of driving as a function of advanced training aimed at
      recognizing and handling risks in demanding driving situations.
AB  - The present study examined in 224 individuals whether an advanced driving
      training aimed at recognizing, avoiding and handling risks in demanding driving
      situations, affected perceived risk of driving situations (measured by a
      questionnaire). The training, which involved both experience and feedback on real
      performance, specifically intended to emphasize the dangers in loss of control of
      a vehicle. With that emphasis, it was hypothesized that perceived risk would
      increase after as compared to before the training. In addition, this study
      examined whether risk perception was dependent on gender or on age. A mixed ANOVA
      performed on mean scores on the questionnaire yielded significant main effects
      for training (before/after), gender, and age. Higher levels of perceived risk
      were reported after the training as compared to before it, by females than by
      males, and by older adult drivers than by younger adult drivers. An analysis of
      the data of a smaller sample showed that the increment in perceived risk was
      still present 2 months after the training, and that it did not decrease
      significantly as compared to immediately after the training. These results are
      discussed in relation to relevant methodological issues and future research.

PMID- 18329424
TI  - The effects of practice with MP3 players on driving performance.
AB  - This study examined the effects of repeated iPod interactions on driver
      performance to determine if performance decrements decreased with practice.
      Nineteen younger drivers (mean age=19.4, range 18-22) participated in a seven
      session study in the University of Calgary Driving Simulator (UCDS). Drivers
      encountered a number of critical events on the roadways while interacting with an
      iPod including a pedestrian entering the roadway, a vehicle pullout, and a lead
      vehicle braking. Measures of hazard response, vehicle control, eye movements, and
      secondary task performance were analyzed. Increases in perception response time
      (PRT) and collisions were found while drivers were performing the difficult iPod
      tasks, which involved finding a specific song within the song titles menu. Over
      the course of the six experimental sessions, driving performance improved in all
      conditions. Difficult iPod interactions significantly increased the amount of
      visual attention directed into the vehicle above that of the baseline condition.
      With practice, slowed responses to driving hazards while interacting with the
      iPod declined somewhat, but a decrement still remained relative to the baseline
      condition. The multivariate results suggest that access to difficult iPod tasks
      while vehicles are in motion should be curtailed.

PMID- 18329425
TI  - Coding external causes of injuries: problems and solutions.
AB  - Complete and accurate information about hospitalised injuries is essential for
      injury risk and outcome research, though the accuracy and reliability of hospital
      data for injury surveillance are often questioned. To ascertain clinical coders'
      views of the reasons for a lack of specificity in external cause code usage and
      ways to improve external cause coding, a nationwide survey of coders was
      conducted in Australia in 2006. Four hundred and two coders participated in the
      questionnaire. The results of this study show that discharge summaries and
      doctors' notes were the poorest source of information regarding external causes,
      place of injury occurrence, and activity at the time of injury. Coders viewed
      missing external cause information and missing documentation as having the
      greatest impact on the quality of external cause coding. A large majority of
      coders suggested that improving clinical documentation in the emergency
      department and introducing a centralised structured form for external cause
      information would improve the quality of external cause coding. Clinical coders
      are a valuable source of information regarding problems with, and solutions to
      the collection of high quality data and this research has highlighted several
      areas where improvements can be made and further research is needed.

PMID- 18329426
TI  - The contribution of stereo vision to the control of braking.
AB  - In this study the contribution of stereo vision to the control of braking in
      front of a stationary target vehicle was investigated. Participants with normal
      (StereoN) and weak (StereoW) stereo vision drove a go-cart along a linear track
      towards a stationary vehicle. They could start braking from a distance of 4, 7,
      or 10m from the vehicle. Deceleration patterns were measured by means of a laser.
      A lack of stereo vision was associated with an earlier onset of braking, but the
      duration of the braking manoeuvre was similar. During the deceleration, the time
      of peak deceleration occurred earlier in drivers with weak stereo vision.
      Stopping distance was greater in those lacking in stereo vision. A lack of stereo
      vision was associated with a more prudent brake behaviour, in which the driver
      took into account a larger safety margin. This compensation might be caused
      either by an unconscious adaptation of the human perceptuo-motor system, or by a
      systematic underestimation of distance remaining due to the lack of stereo
      vision. In general, a lack of stereo vision did not seem to increase the risk of
      rear-end collisions.

PMID- 18329427
TI  - Factors associated with the all-terrain vehicle mortality rate in the United
      States: an analysis of state-level data.
AB  - The purpose of this article is to determine and quantify the factors associated
      with the all-terrain vehicle (ATV) mortality rate in the United States, based on
      an analysis of state-level data. From 1990 through 1999, there were about 2400
      reported deaths in the U.S. involving ATVs. The population-based mortality rate
      during this time period amounted to about 0.84 deaths per million persons per
      year, but varied considerably among the 50 states-ranging from a low of 0.09
      deaths per million person-years in Rhode Island to a high of 6.33 deaths per
      million person-years in West Virginia. This variation provides an opportunity for
      quantifying some of the key factors associated with the ATV mortality risk. The
      analysis was conducted in a two-stage regression process, with the state
      mortality rates estimated in the second stage with a negative binomial regression
      model. The results indicate that the ATV mortality rate was systematically
      related to ATV usage rates (a measure of risk exposure) and a number of the
      characteristics of the potential rider pool. These included: the proportion of
      the state populations that was male, young, lived in rural areas, was college
      educated, and non-Hispanic white.

PMID- 18329428
TI  - The Hispanic Americans Baseline Alcohol Survey (HABLAS): Rates and predictors of
      DUI across Hispanic national groups.
AB  - This paper examines rates of self-reported driving under the influence (DUI) of
      alcohol and 12-month and lifetime DUI arrest rates among Mexican Americans,
      Puerto Ricans, Cuban Americans and South/Central Americans in the U.S.
      population. Using a multistage cluster sample design, a total of 5224 individuals
      18 years of age and older were selected from the household population in five
      metropolitan areas of the U.S.: Miami, New York, Philadelphia, Houston and Los
      Angeles. The survey weighted response rate was 76%. Among men, 21% of Mexican
      Americans, 19.9% of South/Central Americans, 11.6% of Puerto Ricans and 6.9% of
      Cuban Americans reported DUI. Rates were lower among women, ranging from 9.7% for
      Mexican Americans to 1.3% for Cuban Americans. Mexican American men had the
      highest 12-month arrest rate (1.6%) and the highest lifetime arrest rate (11.2%).
      Drinkers who reported DUI were heavier drinkers than those not reporting DUI
      according to a variety of indicators. However, most DUI incidents involved non
      alcohol-dependent drivers. Mexican Americans and South Central/Americans, men,
      younger drivers, those with less than high school education, those with higher
      income and higher alcohol consumption were more likely to report DUI and DUI
      arrests. These findings show that Hispanic national groups in the U.S. are
      diverse regarding drinking and DUI-related experiences.

PMID- 18329429
TI  - Safety effects of blue cycle crossings: a before-after study.
AB  - This paper presents a before-after accident study of marking blue cycle crossings
      in 65 signalised junctions. Corrections factors for changes in traffic volumes
      and accident/injury trends are included using a general comparison group in this
      non-experimental observational study. Analysis of long-term accident trends point
      towards no overall abnormal accident counts in the before period. The safety
      effect depends on the number of blue cycle crossings at the junction. One blue
      cycle crossing reduces the number of junction accidents by 10%, whereas marking
      of two and four blue cycle crossings increases the number of accidents by 23% and
      60%, respectively. Larger reduction and increases are found for injuries. Safety
      gains at junctions with one blue cycle crossing arise because the number of
      accidents with cyclists and moped riders that may have used the blue cycle
      crossing in the after period and pedestrians in the pedestrian crossing parallel
      and just next to the blue marking was statistically significant reduced. Two or
      four blue cycle crossings especially increase the number of rear-end collisions
      only with motor vehicles involved and right-angle collisions with passenger cars
      driving on red traffic lights.

PMID- 18329430
TI  - Validity and reliability of the on-road driving assessment with senior drivers.
AB  - The on-road driving assessment is widely regarded as the criterion measure for
      driving performance despite a paucity of evidence concerning its psychometric
      properties. The purpose of this study was 2-fold. First, we examined the
      psychometric properties of an on-road driving assessment with 100 senior drivers
      between 60 and 86 years (80 healthy volunteers and 20 with specific vision
      deficits) using Rasch modeling. Second, we compared the outcome of the gestalt
      decision made by trained professionals with that based on weighted error scores
      from the standardized assessment. Rasch analysis provided good evidence for
      construct validity and inter-rater reliability of the on-road assessment and some
      evidence for internal reliability. Goodness of fit statistics for all items were
      within an acceptable range and the item hierarchy was logical. The test had a
      moderate reliability index (0.67). The best cut off score yielded sensitivity of
      81% and specificity of 95% compared with the gestalt decision. Further research
      is required with less competent drivers to more fully examine reliability.
      Healthy senior drivers failed to check blind spots when changing lanes and made
      errors when asked to report road markings and traffic signs as they drove. In
      addition unsafe drivers had difficulty negotiating intersections and lane
      changes.

PMID- 18329431
TI  - Safety effects of the separation distances between driveway exits and downstream
      U-turn locations.
AB  - Using U-turns as alternatives to direct left-turns is an important access
      management treatment which has been widely implemented in the United States to
      improve safety on multilane highways. The primary objective of this study is to
      evaluate the safety effects of the separation distances between driveway exits
      and downstream U-turn locations. To achieve the research objective, crash data
      reported at 140 street segments in the state of Florida were investigated. The
      selected sites were divided into three groups based on the separation distances.
      t-Tests and proportionality tests were performed for comparing crash frequency,
      crash type, and crash severity between different separation distance groups.
      Negative-binomial models were developed for examining the factors that contribute
      to the crashes reported at selected sites. The data analysis results show that
      the separation distances significantly impact the safety of the street segments
      between driveways and downstream U-turn locations. A 10% increase in separation
      distance will result in a 3.3% decrease in total crashes and a 4.5% decrease in
      the crashes which is related with right-turns followed by U-turns. The models
      also show that providing U-turns at a signalized intersection will result in more
      crashes at weaving sections. Thus, if U-turns are to be provided at a signalized
      intersection, a longer separation distance shall be provided.

PMID- 18329432
TI  - Tobit analysis of vehicle accident rates on interstate highways.
AB  - There has been an abundance of research that has used Poisson models and its
      variants (negative binomial and zero-inflated models) to improve our
      understanding of the factors that affect accident frequencies on roadway
      segments. This study explores the application of an alternate method, tobit
      regression, by viewing vehicle accident rates directly (instead of frequencies)
      as a continuous variable that is left-censored at zero. Using data from vehicle
      accidents on Indiana interstates, the estimation results show that many factors
      relating to pavement condition, roadway geometrics and traffic characteristics
      significantly affect vehicle accident rates.

PMID- 18329433
TI  - Mitigating driver distraction with retrospective and concurrent feedback.
AB  - OBJECTIVES: An experiment was conducted to assess the effects of retrospective
      and combined retrospective and concurrent feedback on driver performance and
      engagement in distracting activities. BACKGROUND: A previous study conducted by
      the authors showed that concurrent (or real time) feedback can help drivers
      better modulate their distracting activities. However, research also shows that
      concurrent feedback can pose additional distractions due to the limited time and
      resources available during driving. Retrospective feedback, which is presented at
      the end of a trip (i.e., post-drive), can include additional information on
      safety critical situations during a trip and help the driver learn safe driving
      habits. METHOD: A driving simulator study was conducted with 48 participants and
      3 conditions: retrospective feedback, combined feedback (both retrospective and
      concurrent), and no feedback (baseline case). RESULTS: The feedback conditions
      (retrospective and combined) resulted in faster response to lead vehicle braking
      events as depicted by shorter accelerator release times. Moreover, combined
      feedback also resulted in longer glances to the road. CONCLUSIONS: The results
      suggest that both feedback types have potential to improve immediate driving
      performance and driver engagement in distractions. APPLICATION: Combined feedback
      holds the most promise for mitigating the effects of distraction from in-vehicle
      information systems.

PMID- 18329434
TI  - Risk factors and prevention for spinal cord injury from diving in swimming pools
      and natural sites in Quebec, Canada: a 44-year study.
AB  - BACKGROUND: Diving is the most frequent cause of spinal cord injury (SCI) from
      recreation and sport in Canada. This study was done to identify risk factors for
      SCI from diving in the province of Quebec. METHODS: An interview survey was done
      for a target population of 203 subjects with a SCI from diving treated in the two
      specialized rehabilitation centers in Quebec during 1961-2004. Telephone
      interviews of consenting individuals were used to collect pertinent personal,
      equipment, and environmental factors for each incident. RESULTS: Response was 44%
      (89/203); 92% were male and 85% <35 years old. Only 37% were aware prior to
      injury of the risk of SCI from diving, and only 33% had received water safety
      training. Swimming pools were the site of 51% (n=45) and natural bodies of water
      for 49% (n=44). 87% (n=39) of pools were single-unit home pools and 57% (n=26)
      above-ground. Depth indicators were absent for 100% of above-ground and 74% of in
      ground pools. For SCI in in-ground pools, 63% resulted from striking the up-slope
      between deep and shallow ends. For dives at natural sites, a dock or wharf was
      the most frequent location, 36% (n=16). In 52% of pools and 79% of natural sites,
      depth was <1.4m (4.6ft). Signs prohibiting diving were absent in 96% of above
      ground and 89% of in-ground pools. Alcohol was reported in 47% of SCIs.
      INTERPRETATION: The target for prevention of diving SCI is male youths and young
      adults. Above-ground pools are too shallow and small for diving. Deep ends of
      many in-ground pools are excessively shallow and short since many SCIs resulted
      from striking the up-slope. Prevention of SCI from diving needs to focus on
      education of potential victims, pool vendors and manufacturers, and regulations
      for safety norms in private pools. Water safety should highlight diving as a high
      risk activity, and emphasize that most home pools and natural sites are unsafe.
      Safer evidence-based pool designs and more effective warnings need to be
      implemented.

PMID- 18329435
TI  - The Dula Dangerous Driving Index: an investigation of reliability and validity
      across cultures.
AB  - The aim of this study is to further establish the validity and reliability of the
      Dula Dangerous Driving Index (DDDI). The reliability and validity of the
      instrument was investigated by comparing data from a US university sample, a US
      community sample, and a sample of Belgian traffic offenders. Exploratory and
      confirmatory factor analysis supported the presence of a four-factor structure
      with items for Drunk Driving forming a separate scale apart from items for Risky
      Driving, Negative Cognitive/Emotional Driving and Aggressive Driving. A multi
      group confirmatory factor analysis with model constraints supported the validity
      of the DDDI. Inter-correlations revealed that the DDDI subscales are closely
      interrelated and uni-dimensionality of the measure was found in all three
      samples. This suggests the DDDI Total score can be used as a composite measure
      for dangerous driving. However, the validity of the subscales was demonstrated in
      the Belgian sample, as specific traffic offender groups (convicted for drunk
      driving, aggressive driving, speeding) scored higher on corresponding scales
      (Drunk Driving, Aggressive Driving, and Risky Driving, respectively), indicating
      that it is clinically meaningful to differentiate the subscales.

PMID- 18329436
TI  - Safety improvements through Intelligent Transport Systems: a South African case
      study based on microscopic simulation modelling.
AB  - Intelligent Transport Systems (ITS) can facilitate the delivery of a wide range
      of policy objectives. There are six main objectives/benefits identified in the
      international literature: Safety (reduction of (potential) crashes), mobility
      (reduction of delays and travel times), efficiency (optimise the use of existing
      infrastructure), productivity (cost saving), energy/environment and customer
      satisfaction [Mitretek Systems, 2001. Intelligent Transport System Benefits: 2001
      update, Under Contract to the Federal Highway Administration, US Department of
      Transportation, Washington, DC, US]. In the South African context, there is an
      interest for measures that can reduce (potential) crashes. In South Africa the
      number of year on year traffic related fatalities is still increasing. In 2005
      the number of fatalities was 15393 (from 14135 in 2004) while the estimated costs
      for the same period increased from R8.89-billion to R9.99-billion [RTMC, 2007.
      Interim Road Traffic and Fatal Crash Report 2006, Road Traffic Management
      Corporation, Pretoria, SA]. Given the extent of the road safety problem and the
      potential benefits of ITS, the need for further research is apparent. A study
      with regards to the potential of different types of models (macroscopic,
      mesoscopic and miscroscopic simulation models) led to the use of Paramics. Two
      corridors and three types of ITS measures were investigated and safety benefits
      were estimated.

PMID- 18329437
TI  - The consequences of an increase in heavy goods vehicles for passenger car
      drivers' mental workload and behaviour: a simulator study.
AB  - The effects of an increase in Heavy Goods Vehicles (HGVs) on merging behaviour
      and on mental workload of motorists during filtering in and out of traffic were
      studied. Participants drove in a driving simulator in a total of 12 conditions;
      twice in each of two weather conditions and in three traffic conditions. The
      weather conditions were clear weather and foggy weather. The traffic conditions
      were without HGVs (i.e. only private cars), the current mix of HGVs and private
      cars, and a condition with a 70% increase of HGVs leading to an HGV column in the
      slow lane. The focus of the study was on assessing effects on behaviour and
      mental workload during filtering into traffic, and during exiting from the
      motorway. During the experiment driving performance was registered, behaviour was
      observed, self reports were collected, and the participant's heart rate was
      recorded. The results showed that directly after filtering into traffic the
      variation in driving speed increased and the minimum time headway decreased with
      an increase in the proportion of HGVs. Joining motorway traffic was considered to
      involve greater effort and risk in the condition with a column of HGVs. The
      effects of the conditions on heart rate are less clear, although the moment when
      the participants joined the traffic is clearly visible. The effects of weather
      conditions were limited, drivers adapting their driving behaviour in adverse
      weather by reducing speed. To exit the motorway is not a difficult manoeuvre. For
      that reason the lane change from the left hand to the right hand lane that
      preceded the exit was analysed. Although increased mental effort was reported and
      the lane change was visible in the heart rate record, no critical changes as a
      result of increase in proportion of HGVs were found for this manoeuvre. However,
      in the condition with a column of HGVs, the exit that had to be taken was most
      frequently missed as HGVs obstructed the view of the exit signs. It is concluded
      that an increase in HGVs will make merging into traffic more mentally demanding
      and will decrease safety margins.

PMID- 18329438
TI  - Rear seat safer: seating position, restraint use and injuries in children in
      traffic crashes in Victoria, Australia.
AB  - Car crashes are a major cause of death and serious injury to children but most
      analyses of risk are based on US data. The Australian context is different in at
      least three ways: (1) the proportion of passenger-side airbags, a potential risk
      to children in front seats, is much lower; (2) unlike in the US, Australian
      airbags are designed to work with restrained passengers; (3) restraint use for
      children 0-12 years is high (>90%). Official data drawn from Victorian crash
      records (n=30,631) were used to calculate relative risks of death or serious
      injury for children (0-3 years, 4-7 years; 8-12 years) traveling in passenger
      cars during 1993-1998 and 1999-2004. Over 90% were reportedly wearing a
      restraint, and 20% were traveling in the front seat. For children under 4 years
      traveling in the front seat, the relative risk of death was twice as great as
      when traveling in the rear, and that of serious injury was 60% greater. The
      relative risk of death whilst traveling in the front seat was almost four times
      greater for children aged under 1 year. We suggest that serious consideration
      should be given to mandating rear seating for children, particularly those aged 4
      and under.

PMID- 18329439
TI  - Modeling motor vehicle crashes for street racers using zero-inflated models.
AB  - Motor vehicle crashes are a leading cause of death for young people in the United
      States. Assessing which drivers are at a high risk of experiencing a crash is
      important for the implementation of traffic regulations. Illegal street racing
      has been associated with a high rate of motor vehicle crashes. In this study, we
      link Utah statewide driver license citations and motor vehicle crash data to
      evaluate the rate of crashes for drivers with street racing citations relative to
      other drivers. Using a zero-inflated negative binomial model we found that
      drivers with no citations are approximately three times more likely to be at zero
      risk of a crash compared to drivers with street racing citations. Moreover, among
      drivers at non-negligible risk of crash, cited street racers are more likely to
      be involved in a crash compared to drivers without citations or those cited for
      violations other than street racing. However, drivers with increased numbers of
      non-street-racing citations experience crash risks approaching those of the cited
      street racers.

PMID- 18329440
TI  - Masculinity causes speeding in young men.
AB  - The goal of this study was to examine if masculinity is causally responsible for
      speeding in young men. Participants (83 males) were randomly assigned to a
      masculine, feminine, or neutral priming condition. Priming consisted in active
      listening to either masculine, feminine, or neutral words coming from the car
      radio while driving in a high-end driving simulator. Results showed that when the
      concept of masculinity was activated by priming, participants' driving speed
      increased significantly from the beginning to the end of the driving simulation
      as compared to the neutral and the feminine condition. Results are discussed with
      respect to real life health implications.

PMID- 18329441
TI  - The when and where of BDNF and the antidepressant response.

PMID- 18329442
TI  - Dental public health. Preface.

PMID- 18329443
TI  - The practice and infrastructure of dental public health in the United States.
AB  - Dental public health is a unique and challenging American Dental Association
      recognized specialty because the patient is the entire community or population,
      such as a school, neighborhood, city, state, or the nation, with a focus on
      vulnerable populations. Limited resources are maximized through prevention,
      policies, programs, and organized community efforts to respond to great unmet
      needs. Although dental public health professionals are few in number, millions of
      people every day have better oral health because of these professionals, who work
      on the local, state, and national level.

PMID- 18329444
TI  - Financing dental care: trends in public and private expenditures for dental
      services.
AB  - This article examines the financing of dental care in the United States. The
      major issues addressed include the amount and sources of funds, the reasons for
      increased dental care expenditures, the comparison of dental care with other
      medical care expenditures, the policy implications of current trends, and some
      cautious predictions about the financing of dental care in the next 10 to 20
      years. The supply of dental services is expected to increase substantially in the
      next 10 to 20 years with more dental school graduates, a new midlevel
      practitioner, and greater use of allied dental health personnel. Whether the
      supply of services will grow faster than the demand for care is unknown.

PMID- 18329445
TI  - Oral health disparities in the United States.
AB  - Oral health disparities refers to the existence of differences in the incidence,
      prevalence, mortality, and burden of oral diseases and other adverse health
      conditions, as well as the use of health care services, among specific population
      groups in the United States. Existence of disparities in oral health status,
      accessing and using the oral health care delivery system, and receiving treatment
      depending on gender, race or ethnicity, education, income, disability, geographic
      location, and sexual orientation have been documented. Different states have
      initiated a series of steps as tools to document, assess, develop strategies, and
      monitor progress in efforts to eliminate or reduce oral health disparities in the
      United States.

PMID- 18329446
TI  - Multicultural issues in oral health.
AB  - Demographic changes over the coming decades will heighten the challenges to both
      the dental profession and the nation. The expected growth in the numbers of
      racial and ethnic minorities and the concomitant growth of immigrant populations
      are likely to lead to worsening of oral health disparities. Their consequences
      are becoming increasingly evident, as the profession strives to improve the oral
      health of all Americans. The increasing diversity of the population, together
      with the importance of cultural beliefs and behaviors that affect health
      outcomes, will require ways to enhance provider-patient communications and oral
      health literacy. One important means by which to promote oral health in diverse
      populations is to develop a dental workforce that is both culturally and
      linguistically competent, as well as one that is as culturally diverse as the
      American population.

PMID- 18329447
TI  - Oral health literacy: the new imperative to better oral health.
AB  - Effective communication with patients is the cornerstone of quality dental care
      and oral health outcomes. Oral health literacy skills are critical to empowering
      individuals' ability to improve their oral health. A large part of the American
      public has low health literacy skills. Low health literacy contributes to disease
      and is costly. Being able to understand health information and how to obtain
      services is critical to oral health management. The communication skills of the
      dental team are pivotal to increasing oral health literacy skills of Americans.

PMID- 18329448
TI  - Patient- and population-reported outcomes in public health dentistry: oral health
      related quality of life.
AB  - At present no process is in place in the United States to comprehensively monitor
      the national burden of oral diseases from the perspective of oral health-related
      quality of life (OHRQoL), yet available evidence shows that a substantial
      percentage of the adult population rates their oral health poorly. This article
      reviews applications of OHRQoL in dental public health. The authors specifically
      review its use, contributions, and needed advances in: (1) monitoring the impacts
      of oral diseases on OHRQoL at the national level, and in public health
      surveillance at the state and local levels; (2) treatment outcomes research and
      program evaluation; and (3) clinical practice.

PMID- 18329449
TI  - Understanding measurement of dental diseases and research participation in
      practice set-up.
AB  - A general understanding of the measurement of dental diseases can help
      practitioners in the process of assessing the patient's future risk of disease.
      More importantly, as clinical studies shift from the traditional academic setting
      to practice-based networks, practitioners might play a more significant role in
      research. An important issue in oral health disease management in the future will
      be the standardization of clinical criteria and the development of alternative
      mechanisms of data collection for epidemiologic purposes.

PMID- 18329450
TI  - Fluorides in dental public health programs.
AB  - The use of fluorides in dental public health programs has a long history. With
      the availability of fluoridation and other forms of fluorides, dental caries have
      declined dramatically in the United States. This article reviews some of the ways
      fluorides are used in public health programs and discusses issues related to
      their effectiveness, cost, and policy.

PMID- 18329451
TI  - Planning and evaluating community oral health programs.
AB  - Community oral-health programs focus primarily on populations, including those
      who do not seek oral health care. Planning these programs should include
      involvement of the community, broadly defined to include individuals and
      organizations that represent those who can help design and implement it and those
      who could be affected by it. This article provides an overview of systematic
      approaches to planning and evaluating community oral health programs. Such
      approaches help ensure that stakeholders agree on the purpose of the program,
      work toward its success, and contribute toward its continuous improvement.

PMID- 18329452
TI  - Public health issues in geriatric dentistry in the United States.
AB  - The aging United States population living in the new millennium has dental needs
      that are very different and more complex than those experienced by previous older
      adult cohorts during the twentieth century. The type of dental care to be
      provided for older Americans goes way beyond emergency care, extractions and
      denture care. Dental caries is still clearly a public health problem for
      subgroups of older Americans, such as those of lower socioeconomic status, with
      dementia, who are homebound and who are institutionalized. These are also the
      subgroups experiencing greater barriers to accessing dental care. Stakeholders,
      including dental professionals and the dental benefits industry, need to work
      together to develop innovative dental financing programs that will increase older
      Americans access to dental care.

PMID- 18329453
TI  - Improving and maintaining oral health for people with special needs.
AB  - The number of people in the United States population with disabilities and other
      special needs is growing dramatically. These individuals present unique
      challenges for oral health professionals in planning and carrying out dental
      treatment and for the oral health delivery system. Because it has been recognized
      that the current delivery system is not working well for these populations, new
      workforce, financing, and delivery models are beginning to emerge that may hold
      promise for creating and maintaining oral health for currently underserved
      populations, including people with disabilities and other special needs. This
      article discusses the implications of this for the oral health profession,
      describes the challenges of providing oral health services for this population,
      and discusses the implications of these challenges for the organization of the
      oral health delivery system.

PMID- 18329454
TI  - The Research Excellence Framework (REF): a major impediment to free and informed
      debate?

PMID- 18329455
TI  - Envisioning simulation in the future of thoracic surgical education.

PMID- 18329456
TI  - Expert commentary: Cardiothoracic surgical simulation.

PMID- 18329457
TI  - Aprotinin: twenty-five years of claim and counterclaim.

PMID- 18329458
TI  - Aprotinin and cardiac surgery.

PMID- 18329459
TI  - Bleeding in cardiac surgery: the use of aprotinin does not affect survival.
AB  - OBJECTIVE: The antifibrinolytic drug aprotinin has been the most widely used
      agent to reduce bleeding and its complications in cardiac surgery. Several
      randomized trials and meta-analyses have demonstrated it to be effective and
      safe. However, 2 recent reports from a single database have implicated the use of
      aprotinin as a risk for postoperative complications and reduced long-term
      survival. METHODS: In this single-institution observational study involving 7836
      consecutive patients (1998-2006), we assessed the safety of using aprotinin in
      risk reduction strategy for postoperative bleeding. RESULTS: Aprotinin was used
      in 44% of patients. Multivariate analysis identified aprotinin use in risk
      reduction for reoperation for bleeding (odds ratio, 0.51; 95% confidence
      interval, 0.36-0.72; P = .001) and need for blood transfusion postoperatively
      (odds ratio, 0.67; 95% confidence interval, 0.57-0.79; P = .0002). The use of
      aprotinin did not affect in-hospital mortality (odds ratio, 1.03; 95% confidence
      interval, 0.71-1.49; P = 0.73), intermediate-term survival (median follow-up, 3.4
      years; range, 0-8.9 years; hazard ratio, 1.09; 95% confidence interval, 0.93
      1.28; P = .30), incidence of postoperative hemodialysis (odds ratio, 1.16; 95%
      confidence interval, 0.73-1.85; P = .49), and incidence of postoperative renal
      dysfunction (odds ratio, 0.78; 95% confidence interval, 0.59-1.03; P = .07).
      CONCLUSION: This study demonstrates that aprotinin is effective in reducing
      bleeding after cardiac surgery, is safe, and does not affect short- or medium
      term survival.

PMID- 18329460
TI  - Optimal timing of coronary artery bypass after acute myocardial infarction: a
      review of California discharge data.
AB  - OBJECTIVE: The optimal timing for coronary artery bypass grafting after acute
      myocardial infarction is not well established. The California Discharge Database
      facilitates the study of this issue by providing data from a large patient cohort
      free of institutional bias. We examine the timing of coronary artery bypass
      grafting after acute myocardial infarction on short-term outcomes. METHODS: We
      reviewed California Discharge Data to identify 40,159 patients who were
      hospitalized for acute myocardial infarction (day 0) and underwent subsequent
      coronary artery bypass grafting. Patients were stratified by the timing of
      coronary artery bypass grafting to "early" (days 0-2) and "late" groups (day 3 or
      later). The primary outcome variable was all-cause hospital mortality. Multiple
      logistic and linear regression and propensity analyses assessed the risk of
      adverse events, controlling for factors associated with preoperative clinical
      acuity, including the Charlson Comorbidity Index, shock, mechanical ventilation,
      and the use of intra-aortic balloon counterpulsation. RESULTS: Of 9476 patients
      identified, 4676 (49%) were in the early coronary artery bypass grafting group
      and 4800 (51%) were in the late coronary artery bypass grafting group. A total of
      444 patients (4.7%) died during hospitalization, with a peak mortality rate of
      8.2% among patients undergoing coronary artery bypass grafting on day 0,
      declining to a nadir of 3.0% among patients undergoing coronary artery bypass
      grafting on day 3. The mean time to coronary artery bypass grafting was 3.2 days.
      Patients undergoing early coronary artery bypass grafting experienced a higher
      mortality rate than those undergoing late coronary artery bypass grafting (5.6%
      vs 3.8%, P < .001). Early coronary artery bypass grafting was an independent
      predictor of mortality after controlling for clinical acuity and on propensity
      analysis (odds ratio 1.43, P = .003). CONCLUSION: Patients undergoing coronary
      artery bypass grafting within 2 days of hospitalization for acute myocardial
      infarction experienced higher mortality rates than those undergoing coronary
      artery bypass grafting 3 or more days after acute myocardial infarction,
      independently of clinical acuity. This suggests that coronary artery bypass
      grafting may best be deferred for 3 or more days after admission for acute
      myocardial infarction in nonurgent cases.

PMID- 18329462
TI  - Solid and gaseous cerebral microembolization after biologic and mechanical aortic
      valve replacement: investigation with multirange and multifrequency transcranial
      Doppler ultrasound.
AB  - OBJECTIVE: Cerebral microembolization is a well-recognized phenomenon after
      cardiac valve replacement, but the relative proportion of solid and gaseous
      emboli is uncertain. Particulate microemboli are thought to be the most damaging.
      With the use of multifrequency transcranial Doppler ultrasound, we compared the
      number and nature of microemboli in recipients of biologic and mechanical aortic
      valve prostheses. METHODS: The middle cerebral arteries of 60 patients were
      monitored bilaterally with a new-generation transcranial Doppler ultrasound (Embo
      Dop, DWL Elektronische Systeme GmbH, Singen, Germany) that rejects artefacts
      online and automatically discriminates between solid and gaseous microemboli. All
      recordings were performed during a 30-minute period 1 day before and at a mean of
      5 days and 3 months after isolated aortic valve replacement with a biologic (30,
      group B) or mechanical (30, group M) prosthesis. RESULTS: The patients in group B
      were older, with a mean age of 70.6 +/- 9.7 years versus 55.4 +/- 9.4 years (P <
      .005) in the patients in group M. Biologic prosthesis recipients were all taking
      aspirin (no warfarin); patients with mechanical valves were well anticoagulated
      with warfarin both 5 days and 3 months after surgery. None of the patients had
      solid microemboli preoperatively. Five days postoperatively, the absolute number
      of cerebral microemboli was 145 and 594 for total microemboli (P = .001) and 41
      and 182 for solid microemboli (P = .002) in groups B and M, respectively. At 3
      months, the absolute number was 65 and 608 for total microemboli (P < .001) and
      10 and 188 for solid microemboli (P < .001) in groups B and M, respectively.
      Solid microemboli accounted for 16% of the total microembolic load in group B
      compared with 31% in group M (P = .05) at 3 months. CONCLUSIONS: Solid cerebral
      microemboli represent approximately one third of the total cerebral microembolic
      load after mechanical aortic valve replacement and are detectable in the majority
      of such patients both 5 days and 3 months after surgery. The neurofunctional
      consequences of this phenomenon should be carefully assessed.

PMID- 18329463
TI  - On-pump beating-heart coronary artery bypass grafting after acute myocardial
      infarction has lower mortality and morbidity.
AB  - OBJECTIVE: The mortality of conventional coronary artery bypass grafting after
      acute myocardial infarction remains high. This study compared the clinical
      outcomes of patients undergoing conventional and on-pump beating-heart coronary
      artery bypass grafting and evaluated the efficacy of an on-pump beating-heart
      technique for the surgical treatment of these critically ill patients. METHODS:
      Between January 1999 and March 2005, 61 patients underwent emergency coronary
      artery bypass grafting for acute myocardial infarction. In the first 23 patients,
      the conventional cardioplegic method was performed. In the most recent 38
      patients, the on-pump beating-heart procedure was used without cardioplegic
      arrest. RESULTS: A significant reduction occurred in the observed mortality
      between the conventional and on-pump beating groups (21.7% vs 2.6%, P = .04),
      despite a higher predicted mortality risk calculated by using EuroSCORE (9.0 +/-
      1.6 vs 9.6 +/- 1.6, P = .048) and a greater use of a preoperative intra-aortic
      balloon pump (43.5% vs 78.9%, P = .005). On-pump beating-heart patients received
      fewer bypass grafts than conventional patients (2.0 vs 2.9, P = .001), but the
      internal thoracic artery was used more often in on-pump beating-heart patients (P
      = .014). Three patients in the conventional coronary artery bypass grafting group
      required new insertion of an intra-aortic balloon pump, whereas no patients
      required this in the on-pump beating-heart group (P = .220). Postoperative renal
      failure requiring hemodialysis occurred in 2 patients in the conventional
      coronary artery bypass grafting group but in no patients in the on-pump beating
      heart group (P = .138). CONCLUSIONS: On-pump beating-heart coronary artery bypass
      grafting is the preferred method of emergency myocardial revascularization for
      patients with acute myocardial infarction who might tolerate cardioplegic arrest
      poorly. It has lower postoperative mortality and morbidity than conventional
      coronary artery bypass grafting.

PMID- 18329464
TI  - Ten-year experience with single-vessel and multivessel reoperative off-pump
      coronary artery bypass grafting.
AB  - OBJECTIVE: Patients undergoing reoperative coronary artery bypass have increased
      mortality and morbidity compared with those undergoing primary coronary bypass.
      The experience in applying off-pump techniques to coronary reoperations is
      limited. In this article we report a 10-year experience using various techniques
      of reoperative off-pump coronary bypass. METHODS: Between January 1996 and
      December 2005, 332 patients underwent reoperative off-pump coronary artery bypass
      grafting. Data were collected regarding the preoperative, intraoperative, and
      postoperative clinical course of all patients. These were compared with similar
      data obtained from patients who had undergone conventional coronary reoperation
      during this period. RESULTS: Two hundred ninety-six (89.2%) male and 36 female
      patients underwent reoperative off-pump coronary artery bypass. Of these, 265
      (79.8%) patients underwent multivessel bypass through a median sternotomy, an
      anterolateral thoracotomy was performed in 63 (19%) patients, and a
      posterolateral thoracotomy was performed in 4 (1.2%) patients. The early
      mortality for patients undergoing off-pump surgery was lower than for those
      undergoing conventional reoperations (3.3% vs 5.5%, P = .066). Those who had
      undergone off-pump reoperations had less need for prolonged ventilation or
      prolonged inotropic support and had shorter intensive care unit and hospital
      stays than patients who had undergone redo coronary artery bypass grafting.
      CONCLUSION: For many patients requiring coronary reoperations, off-pump
      techniques are safe and feasible. Complete revascularization was achieved in at
      least 75% of patients in an unselected population, with mortality and
      perioperative event rates that are comparable with those of conventionally
      performed coronary reoperations.

PMID- 18329465
TI  - The effects of on-pump and off-pump coronary artery bypass grafting on
      intraoperative graft flow in arterial and venous conduits defined by a
      flow/pressure ratio.
AB  - OBJECTIVE: Despite profound differences in the neurohumoral milieu in patients
      undergoing on-pump and off-pump coronary artery bypass grafting, it is uncertain
      how this affects graft blood flow. METHODS: We prospectively recorded
      intraoperative transit-time flow measurements (MediStim BF 2004; MediStim AS,
      Oslo, Norway) in all internal thoracic artery, radial artery, and long saphenous
      vein conduits in patients undergoing off-pump and on-pump bypass grafting by a
      single surgeon. We calculated a flow/pressure ratio as a ratio of mean graft flow
      to mean arterial pressure for all the conduits just before chest closure.
      RESULTS: Transit-time flow measurements were recorded in 266 grafts (203 off
      pump; 63 on-pump) in 100 patients (80 off-pump; 20 on-pump). Overall, mean graft
      flow (milliliters per minute) was higher for all grafts in the on-pump group
      despite a significantly lower mean arterial pressure compared with the off-pump
      group (P < .05). Consequently the flow/pressure ratio was greater for all grafts
      in the on-pump group (internal thoracic artery 0.55 vs 0.35, radial artery 0.61
      vs 0.36, long saphenous vein 0.77 vs 0.55). Overall mean graft flow was
      significantly greater in the long saphenous vein than in the internal thoracic
      artery (P < .001) and radial artery (P = .001), but there was no significant
      difference in mean graft flow in internal thoracic artery or radial artery grafts
      within each group. CONCLUSIONS: In comparison with the off-pump group, the
      overall mean graft flow and flow/pressure ratio were significantly higher and
      mean arterial pressure significantly lower for all grafts in the on-pump group.
      These findings are probably a result of vasodilatation resulting from
      cardiopulmonary bypass and reactive hyperemia resulting from a period of
      ischemia. There was no difference in the mean graft flow and flow/pressure ratio
      of arterial grafts, which were significantly less than for long saphenous vein
      grafts. In patients with unstable angina and/or hemodynamic instability, in whom
      rapid and maximum restoration of myocardial perfusion is a priority, potentially
      lower graft flow in arterial grafts and off-pump surgery should be considered.

PMID- 18329466
TI  - Risk factors for wound infection after off-pump coronary artery bypass grafting:
      should bilateral internal thoracic arteries be harvested in patients with
      diabetes?
AB  - OBJECTIVE: Wound infection is a rare but life-threatening complication after
      coronary artery bypass grafting. Risk factors for wound infection after off-pump
      bypass grafting and the validity of using bilateral internal thoracic arteries
      harvested in a skeletonized fashion remain unclear, especially in patients with
      diabetes. METHODS: The data of 1500 consecutive patients having off-pump bypass
      grafting were prospectively collected from our database based on EuroSCORE. This
      cohort represents 95% of all patients undergoing coronary bypass during that
      period and 77% of patients undergoing off-pump bypass grafting who received
      bilateral internal thoracic artery grafts. Univariate and multivariate analyses
      were performed for patients with and without wound infection and in the diabetic
      subgroup. RESULTS: Ninety-eight patients had wound infections: 76, impaired wound
      healing; 7, superficial sternal wound infection; and 12, deep sternal wound
      infection. Patients with wound infections had a higher prevalence of female
      gender, atrial fibrillation, history of congestive heart failure, chronic renal
      failure, peripheral vascular disease, and diabetes. Patients with a wound
      infection more frequently had bilateral internal thoracic artery grafting, longer
      operation time, longer hospital stay, and a higher mortality rate. Blood
      transfusions were required in 43.9% of patients with wound infections and 28.1%
      of those without wound infections. On logistic regression analysis, female gender
      and history of congestive heart failure, chronic renal failure, and diabetes
      mellitus were independent risk factors for wound infection. In patients with
      diabetes, female gender, atherosclerosis obliterans, chronic renal failure, and
      use of bilateral internal thoracic artery grafts were independent risk factors
      for wound infection. CONCLUSIONS: Risk factors for wound infection after off-pump
      coronary artery bypass grafting are comparable with those previously reported for
      conventional bypass grafting. In patients with diabetes, the use of bilateral
      internal thoracic arteries, even when harvested in a skeletonized fashion, is a
      risk factor. Thus, appropriate precautions should be taken in patients with
      diabetes.

PMID- 18329467
TI  - Cardiac surgery in infants with low birth weight is associated with increased
      mortality: analysis of the Society of Thoracic Surgeons Congenital Heart
      Database.
AB  - OBJECTIVE: The evaluation of operative mortality risk for cardiac surgery in
      infants with low weight is limited. To determine whether low weight is a risk
      factor for increased mortality, we reviewed the experience within the Society of
      Thoracic Surgeons Congenital Heart Surgery Database of infants who have undergone
      surgical correction or palliation for congenital heart disease. METHODS: We
      analyzed mortality in 3022 infants ages 0 to 90 days weighing 1 to 2.5 kg (n =
      517) and greater than 2.5 to 4 kg (n = 2505) who underwent cardiac surgery from
      2002 through 2004 at 32 participating centers. Patients were grouped according to
      the primary procedure performed and analyzed according to their weight at the
      time of surgical intervention. Patients were also analyzed according to Risk
      Adjustment for Congenital Heart Surgery-1 and Aristotle Basic Complexity scores.
      RESULTS: Compared with infants weighing 2.5 to 4 kg, infants weighing less than
      2.5 kg had a significantly higher mortality for the following operations: repair
      of coarctation of the aorta, total anomalous pulmonary venous connection repair,
      arterial switch procedure, systemic to pulmonary artery shunt, and the Norwood
      procedure. Lower infant weight remained strongly associated with mortality risk
      after stratifying the population by Risk Adjustment for Congenital Heart Surgery
      1 levels 2 through 6 and Aristotle Basic Complexity levels 2 through 4.
      CONCLUSIONS: Low weight at the time of surgical intervention is associated with
      increased mortality in patients undergoing several types of cardiovascular
      procedures. These data do not allow assessment of specific risks or benefits of
      any particular treatment strategy. However, they do support the need for
      prospective analysis of specific treatment strategies for these high-risk
      patients.

PMID- 18329469
TI  - Surgical aortic valvuloplasty in children and adolescents with aortic
      regurgitation: acute and intermediate effects on aortic valve function and left
      ventricular dimensions.
AB  - OBJECTIVE: Surgical aortic valvuloplasty is increasingly employed in the
      management of children and adolescents with aortic regurgitation, but the
      durability of this approach and factors associated with outcome are not well
      defined. METHODS: From 1989 to 2005, a total of 81 patients younger than 19 years
      with moderate or severe aortic regurgitation underwent surgical aortic
      valvuloplasty. Aortic regurgitation was congenital in 20 cases, after treatment
      of aortic stenosis in 30, from other injuries to the aortic valve in 12, and from
      other causes in 19. Eighteen patients had moderate or severe aortic stenosis.
      Preoperative left ventricular end-diastolic dimension z score was 4.9 +/- 2.7.
      RESULTS: After surgical aortic valvuloplasty with various techniques, including
      pericardial leaflet augmentation in 80%, aortic regurgitation was improved in 77
      patients and was mild or less in 68. Ten of 18 patients with moderate or severe
      aortic stenosis before repair had a decrease to mild, whereas 2 had progression
      from mild to moderate. Left ventricular end-diastolic dimension z score decreased
      by 2.9 +/- 2.1 (P < .001). During follow-up (median 4.7 years), 33 patients
      underwent aortic valve reinterventions, including aortic valve replacement in 25.
      Estimated freedoms from aortic valve replacement were 72% +/- 6% at 5 years and
      54% +/- 9% at 7.5 years and were shorter in patients with moderate or severe
      aortic stenosis before surgical aortic valvuloplasty. Among surviving patients
      who did not undergo aortic valve replacement, aortic regurgitation at follow-up
      was moderate in 21 and trivial or mild in 34; left ventricular and aortic root
      dimensions were preserved. CONCLUSION: Surgical aortic valvuloplasty is a valid
      option with good intermediate results for children and adolescents with aortic
      regurgitation from a variety of causes, particularly for patients with less than
      moderate aortic stenosis.

PMID- 18329470
TI  - Noninvasive assessment of liver fibrosis in patients with Fontan circulation
      using transient elastography and biochemical fibrosis markers.
AB  - OBJECTIVE: Studies have shown that patients with failing Fontan circulation may
      develop liver cirrhosis with its sequelae. Therefore, early detection of fibrosis
      is essential to identify patients at risk. Transient elastography has been
      evaluated for noninvasive staging of liver fibrosis in a multitude of studies.
      METHODS: A total of 39 patients who underwent the Fontan procedure were included
      in the study. All patients underwent an abdominal ultrasound, transient
      elastography, and detailed laboratory testing. Conventional echocardiography
      assessment of inflow and outflow and ventricular function were performed.
      RESULTS: Significant signs of liver fibrosis were found in 36 of 39 children
      according to the elastography method and in 28 of 39 children according to the
      measured biochemical fibrosis markers. The Spearman correlation coefficient
      between the liver stiffness measured with transient elastography and the time
      interval since the Fontan operation was highly significant (0.514, P = 0.001).
      CONCLUSION: The present study shows that patients who undergo the Fontan
      procedure are at increased risk of developing liver fibrosis and liver cirrhosis.
      The risk increases with the age of the patient and the time interval since the
      Fontan procedure. The noninvasive measurement of liver fibrosis using transient
      elastography and fibrosis marker scores can be a useful tool to identify patients
      at risk and for noninvasive surveillance.

PMID- 18329471
TI  - Acute angulation of the aortic arch predisposes a patient to ascending aortic
      dilatation and aortic regurgitation late after the arterial switch operation for
      transposition of the great arteries.
AB  - OBJECTIVE: We assessed the contribution of acute aortic arch angulation and
      enhanced systolic pulse wave reflection to dilatation of the ascending aorta and
      aortic regurgitation late after the arterial switch operation for transposition
      of the great arteries. METHODS: We performed aortography, radial artery
      applanation tonometry, and transthoracic echocardiography in 47 children (aged 5
      6 years) who underwent the arterial switch operation and in 20 matched healthy
      controls. The aortic arch angle, ratio of ascending/descending aortic diameter,
      degree of aortic regurgitation, central pulse pressure, aortic augmentation
      pressure, and augmentation index were measured. RESULTS: The aortic arch angle
      was more acute (55 +/- 6.5 degrees vs 68 +/- 5 degrees, respectively, P < .001)
      and the ratio of the ascending/descending aorta diameter was significantly
      greater (1.98 +/- 0.4 vs 1.55 +/- 0.06, respectively, P < .001) in the patients
      who underwent the arterial switch operation compared with controls. Augmentation
      pressure and augmentation index were higher in the patients who underwent the
      arterial switch operation than in controls (7.5 +/- 4.6 vs 3.4 +/- 5.8,
      respectively P = .04; 21 +/- 10 vs 8 +/- 13, respectively, P = .005). A more
      acute aortic angle was associated with a higher aortic augmentation index (r =
      0.41, P < .01), a greater ratio of the ascending to descending aorta (r = -0.6, P
      < .001), and the degree of aortic regurgitation (r = 0.39, P < .01). CONCLUSION:
      Sharper angulation of the aortic arch is associated with early pulse wave
      reflection, dilatation of the ascending aorta, and aortic regurgitation late
      after the arterial switch operation for transposition of the great arteries.

PMID- 18329472
TI  - Aprotinin confers neuroprotection by reducing excitotoxic cell death.
AB  - OBJECTIVE: Aprotinin is used in cardiac surgery for its anti-inflammatory and
      hemostatic benefits. Recent reports describe the neuroprotective effects of other
      serine protease inhibitors via reduced excitotoxic cell death, a common pathway
      causing cytotoxic edema induced in various neuropathologic conditions. The
      purpose of this study was to investigate whether aprotinin directly protects
      against glutamatergic excitotoxicity in cell cultures. METHODS: Mixed cortical
      cultures containing neuronal and glial cells were prepared from fetal mice at 13
      to 15 days' gestation and plated on a layer of confluent astrocytes from 1- to 3
      day-old postnatal pups. Near-pure neuronal culture containing less than 5%
      astrocytes was obtained from the same gestational stage and plated in multiwell
      vessels previously coated with poly-D-lysine and laminin. Both cultures were used
      at 12 to 14 days in vitro. Slowly triggered excitotoxicity was induced at 37
      degrees C by 24-hour exposure to 12.5 microM N-methyl-D-aspartate or 50 microM
      kainate. Neuronal death was quantified by measuring the release of lactate
      dehydrogenase from damaged cells into the bathing medium. Data were analyzed by
      analysis of variance with post hoc Bonferroni comparisons. RESULTS: Aprotinin at
      a clinically relevant concentration of 100 KIU/mL significantly reduced N-methyl
      D-aspartate-induced neuronal death in both pure and mixed cultures (P < .001).
      Aprotinin also reduced neuronal death induced by kainate from 36% to 23% in mixed
      cortical culture (P = .008) and from 40% to 27% in near-pure culture (P = .015),
      indicating that the neuroprotective effects of aprotinin are mediated directly
      through neurons. CONCLUSION: Aprotinin provides direct neuroprotection against
      glutamatergic excitotoxicity as demonstrated by reduced neuronal death in near
      pure neuronal cell culture. Additional studies are needed to evaluate the
      potential of aprotinin to reduce neurologic injury in patients at high risk of
      cerebral injury, including those undergoing circulatory arrest.

PMID- 18329474
TI  - Extracorporeal membrane oxygenation support improves survival of patients with
      severe Hantavirus cardiopulmonary syndrome.
AB  - OBJECTIVE: The purposes of this study are to evaluate the outcome of
      extracorporeal membrane oxygenation support in a subgroup of patients with
      Hantavirus cardiopulmonary syndrome who had a predicted mortality of 100% and to
      assess the complications associated with this treatment modality and with
      different cannulation techniques. METHODS: Thirty-eight patients with severe
      Hantavirus cardiopulmonary syndrome were supported with extracorporeal membrane
      oxygenation between April 1994 and June 2006. Cannulation of the femoral vessels
      was performed on an emergency basis by a percutaneous approach in 15 (39.5%) and
      by an open technique in 23 (60.5%) patients. Duration of extracorporeal membrane
      oxygenation averaged 132 hours (range: 5-276 hours). RESULTS: Complications from
      percutaneous cannulation occurred in 4 (26.6%) of 15 patients: retroperitoneal
      hematoma in 2 (13.3%) and lower extremity ischemia in 2 (13.3%) patients, which
      resolved after insertion of a distal perfusion cannula. Complications from open
      femoral cannulation occurred in 8 (34.8%) of 23 patients: severe bleeding in 7
      (30.4%) patients and lower extremity ischemia in 1 (4.3%) patient who required a
      leg amputation. The overall survival was 60.5% (23/38 patients). Six (40%) of the
      15 patients cannulated percutaneously and 9 (39.1%) of 23 patients who had open
      cannulation died. All survivors recovered completely and were discharged from the
      hospital after a mean hospital stay of 20.8 days (range: 10-39 days).
      CONCLUSIONS: Almost two thirds of the patients with severe Hantavirus
      cardiopulmonary syndrome who were supported with extracorporeal circulation
      survived and recovered completely. The complications associated with both types
      of femoral cannulation may be attributed to the fact that all patients were in
      shock or in full cardiac arrest, and the procedure had to be done expeditiously.
      Earlier institution of extracorporeal membrane oxygenation may decrease the
      complication rates and improve the overall survival.

PMID- 18329475
TI  - Inhibition of mitochondrial remodeling by cyclosporine A preserves myocardial
      performance in a neonatal rabbit model of cardioplegic arrest.
AB  - OBJECTIVE: Mitochondrial permeability transition pore opening is associated with
      apoptotic signaling and alterations in mitochondrial structure and function. We
      tested whether inhibition of mitochondrial permeability transition pore opening
      with cyclosporine A preserved mitochondrial structure and function after
      cardioplegic arrest and whether this preservation is associated with improved
      myocardial performance. METHODS: Langendorff-perfused neonatal rabbit hearts were
      perfused for 30 minutes with Krebs-Henseleit buffer (CCP; n = 6) or Krebs
      Henseleit buffer containing 2 mumol/L of cyclosporine A (CCP+CsA; n = 6) followed
      by 60 minutes of normothermic crystalloid cardioplegia (CCP) and 60 minutes of
      reperfusion. Control hearts (non-CCP; n = 6) were constantly perfused for 150
      minutes without cardioplegic arrest. RESULTS: In comparison with non-CCP, CCP was
      associated with Bax translocation to the mitochondria, cytochrome c release, and
      greater frequency of terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling-positive myocytes These changes were also associated with deficits in
      isolated mitochondrial oxygen consumption at complex I. CsA pretreatment
      minimized or prevented all these findings. Myocardial performance (systolic
      pressure, maximum positive and negative dP/dt, and elevated left ventricular end
      diastolic pressure) at 5, 15, 30, and 60 minutes after reperfusion was diminished
      in CCP hearts when compared with non-CPB, and these deficits could be minimized
      with cyclosporine A pretreatment. (P < .05 all comparisons) CONCLUSIONS:
      Cyclosporine A prevents apoptosis-related mitochondrial permeabilization and
      dysfunction after cardioplegic arrest. This protection is associated with
      improved myocardial performance. Prevention of mitochondrial permeability
      transition pore opening is a valuable target for mitochondrial (and myocardial)
      preservation after neonatal cardioplegic arrest.

PMID- 18329476
TI  - Effects of induction immunosuppression regimen on acute rejection, bronchiolitis
      obliterans, and survival after lung transplantation.
AB  - OBJECTIVE: Effects of daclizumab and antithymocyte globulin induction on acute
      rejection, bronchiolitis obliterans syndrome, and survival after lung
      transplantation are unknown. We hypothesized that daclizumab results in less
      acute rejection and bronchiolitis obliterans and better survival than
      antithymocyte globulin. METHODS: Consecutive adult lung transplants (n = 163) at
      the University of Virginia from January 1998 to May 2006 were reviewed.
      Antithymocyte globulin induction was routinely performed before January 2002 (65
      patients), after which all patients received daclizumab (98 patients). Estimates
      of cumulative event rate of acute rejection, bronchiolitis obliterans, and death
      were calculated by Kaplan-Meier method and between-group differences compared by
      log-rank test. Cox proportional hazards models were fitted to assess treatment
      effects adjusted for covariates. RESULTS: Groups were similar in demographics and
      preoperative and intraoperative risk factors. Maintenance immunosuppression
      changed during the study, and mycophenolate mofetil was more commonly given to
      patients receiving daclizumab. By Kaplan-Meier method, daclizumab was associated
      with significantly less acute rejection (P = .002), less bronchiolitis obliterans
      (P = .02), and improved overall survival (P = .04). Induction agent was highly
      associated with acute rejection (P = .002), bronchiolitis obliterans (P = .02),
      and mortality (P = .05); antimetabolite agent was associated only with acute
      rejection (P = .01). Adjusting for covariates, induction agent remained
      significantly predictive for acute rejection (P = .02) and bronchiolitis
      obliterans (P = .05), approaching significance for survival (P = .07).
      CONCLUSION: Lung transplant recipients receiving daclizumab for induction had
      significantly less acute rejection and bronchiolitis obliterans than those
      receiving antithymocyte globulin, with possibly improved survival. Improvements
      in acute rejection may have been confounded by the use of mycophenolate mofetil.

PMID- 18329478
TI  - Beating-heart patch closure of muscular ventricular septal defects under real
      time three-dimensional echocardiographic guidance: a preclinical study.
AB  - OBJECTIVES: Safe and effective device closure of ventricular septal defects
      remains a challenge. We have developed a transcardiac approach to close
      ventricular septal defects using a patch delivery and fixation system that can be
      secured under real-time three-dimensional echocardiographic guidance. METHODS: In
      Yorkshire pigs (n = 8) a coring device was introduced into the left ventricle
      through a purse-string suture placed on the left ventricular apex, and a muscular
      ventricular septal defect was created. The patch deployment device containing a
      20-mm polyester patch was advanced toward the ventricular septal defect through
      another purse-string suture on the left ventricular apex, and the patch was
      deployed under real-time three-dimensional echocardiographic guidance. The anchor
      delivery device was then introduced into the left ventricle through the first
      purse-string suture. Nitinol anchors to attach the patch around the ventricular
      septal defect were deployed under real-time three-dimensional echocardiographic
      guidance. After patch attachment, residual shunts were sought by means of two
      dimensional and three-dimensional color Doppler echocardiography. The heart was
      then excised, and the septum with the patch was inspected. RESULTS: A ventricular
      septal defect was created in the midventricular (n = 4), anterior (n = 2), and
      apical (n = 2) septum. The mean size was 9.8 mm (8.2-12.0 mm), as determined by
      means of two-dimensional color Doppler scanning. The ventricular septal defects
      were completely closed in 7 animals. In one a 2.4-mm residual shunt was
      identified. No anatomic structures were compromised. CONCLUSIONS: Beating-heart
      perventricular muscular ventricular septal defect closure without cardiopulmonary
      bypass can be successfully achieved by using a catheter-based patch delivery and
      fixation system under real-time three-dimensional echocardiographic guidance.
      This approach might be a better alternative to cardiac surgery or transcatheter
      device closure.

PMID- 18329479
TI  - Endoscopic placement of multiple artificial chordae with robotic assistance and
      nitinol clip fixation.
AB  - OBJECTIVE: A totally endoscopic method of placing multiple premeasured artificial
      chordae with the assistance of the da Vinci surgical system (Intuitive Surgical
      Inc, Sunnyvale, Calif) and V60 U-clip devices (Medtronic Inc, Minneapolis, Minn)
      was evaluated. METHODS: Totally endoscopic placement of multiple artificial
      chordae with robotic assistance and nitinol clips was performed in 30 patients.
      After subvalvular exposure with a robotically controlled Atrial Retractor
      (Intuitive Surgical Inc), artificial chordae constructed of 4-0
      polytetrafluoroethylene (Gore-Tex; WL Gore & Associates Inc, Flagstaff, Ariz)
      were secured to the prolapsing leaflet edge with V60 U-clips. Transesophageal
      echocardiography to assess successful repair was performed. RESULTS: Repairs of
      the anterior leaflet, the posterior leaflet, and combinations of both were
      performed. Crossclamp and cardiopulmonary bypass times were in the range of 78.63
      +/- 17.03 minutes and 118.17 +/- 22.55 minutes, respectively. Transesophageal
      echocardiography showed grade 0 to less than grade 1 mitral regurgitation
      postoperatively. All patients had an uneventful recovery phase and were
      discharged within 5 days. CONCLUSION: Endoscopic placement of premeasured
      artificial neochordae is greatly facilitated by applying robotic assistance and
      using nitinol clips for chordae fixation. The endoscopic robotic technique
      provides excellent functional and clinical outcomes.

PMID- 18329480
TI  - Mediastinoscopy might not be necessary in patients with non-small cell lung
      cancer with mediastinal lymph nodes having a maximum standardized uptake value of
      less than 5.3.
AB  - OBJECTIVE: Accurate pretreatment staging in non-small cell lung cancer remains
      tantamount in formulating an appropriate treatment plan. The maximum standardized
      uptake value obtained with integrated fluorodeoxyglucose-positron emission
      tomography/computed tomography has been proposed to be a predictor of malignancy
      in mediastinal lymph nodes. A recent study has also suggested that accuracy of
      integrated fluorodeoxyglucose-positron emission tomography/computed tomography
      might be improved by increasing the maximum standardized uptake value used for
      calling a lymph node positive from 2.5 to 5.3. We tested the hypotheses that the
      maximum standardized uptake value is a predictor of individual lymph node
      metastasis in non-small cell lung cancer and that pathologic staging with
      mediastinoscopy might not be necessary in patients with a maximum standardized
      uptake value of less than 5.3 in their mediastinal lymph nodes. METHODS: This is
      a retrospective review of 765 lymph nodes sampled from 110 patients in a single
      institution with biopsy-proved non-small cell lung cancer. All patients underwent
      integrated fluorodeoxyglucose-positron emission tomography/computed tomography
      before biopsy or resection of their mediastinal lymph nodes. Surgical staging was
      the reference standard. All N2 lymph nodes were individually assessed according
      to station. Data were analyzed by using the Pearson chi(2) test. RESULTS: Twenty
      one (19%) of 110 patients had N2 disease, and a total of 765 N2 lymph nodes were
      pathologically examined. The mean and median maximum standardized uptake values
      for N2 nodes with metastatic disease were 9.2 (95% confidence interval, 7.0-11.4)
      and 7.2 (range, 2.2-25.8), respectively. For benign N2 nodes, the mean and median
      maximum standardized uptake values were 1.5 (95% confidence interval, 1.4-1.6)
      and 1.0 (range, 1.0-9.6), respectively (P < .05). When integrated
      fluorodeoxyglucose-positron emission tomographic/computed tomographic scans were
      reinterpreted by using a maximum standardized uptake value of 5.3 as a cutoff for
      malignancy, sensitivity decreased from 93% to 81% (P = .15), specificity
      increased from 86% to 98% (P < .01), positive predictive value increased from 22%
      to 64% (P < .01), negative predictive value was unchanged at 99%, and overall
      accuracy of integrated positron emission tomography/computed tomography increased
      from 87% to 97% (P < .01). CONCLUSIONS: The maximum standardized uptake value is
      a predictor of individual lymph node metastasis in non-small cell lung cancer.
      Accuracy of integrated positron emission tomography/computed tomography is
      significantly improved by using a maximum standardized uptake value of 5.3 to
      assign malignancy, thereby dramatically decreasing the number of false-positive
      results. More importantly, these results suggest that some patients with non
      small cell lung cancer with a maximum standardized uptake value less than 5.3 in
      their N2 lymph nodes might be able to forego mediastinoscopy and proceed directly
      to thoracotomy. This represents a significant change in the current management of
      standardized uptake value-positive mediastinal lymph nodes in non-small cell lung
      cancer.

PMID- 18329481
TI  - Extrapleural pneumonectomy versus pleurectomy/decortication in the surgical
      management of malignant pleural mesothelioma: results in 663 patients.
AB  - OBJECTIVE: The optimal procedure for resection of malignant pleural mesothelioma
      is controversial, partly because previous analyses include small numbers of
      patients. We performed a multi-institutional study to increase statistical power
      to detect significant differences in outcome between extrapleural pneumonectomy
      and pleurectomy/decortication. METHODS: Patients with malignant pleural
      mesothelioma who underwent extrapleural pneumonectomy or
      pleurectomy/decortication at 3 institutions were identified. Survival and
      prognostic factors were analyzed by the Kaplan-Meier method, log-rank test, and
      Cox proportional hazards analysis. RESULTS: From 1990 to 2006, 663 consecutive
      patients (538 men and 125 women) underwent resection. The median age was 63 years
      (range, 26-93 years). The operative mortality was 7% for extrapleural
      pneumonectomy (n = 27/385) and 4% for pleurectomy/decortication (n = 13/278).
      Significant survival differences were seen for American Joint Committee on Cancer
      stages 1 to 4 (P < .001), epithelioid versus non-epithelioid histology (P <
      .001), extrapleural pneumonectomy versus pleurectomy/decortication (P < .001),
      multimodality therapy versus surgery alone (P < .001), and gender (P < .001).
      Multivariate analysis demonstrated a hazard rate of 1.4 for extrapleural
      pneumonectomy (P < .001) controlling for stage, histology, gender, and
      multimodality therapy. CONCLUSION: Patients who underwent
      pleurectomy/decortication had a better survival than those who underwent
      extrapleural pneumonectomy; however, the reasons are multifactorial and subject
      to selection bias. At present, the choice of resection should be tailored to the
      extent of disease, patient comorbidities, and type of multimodality therapy
      planned.

PMID- 18329483
TI  - A simple two-gene prognostic model for adenocarcinoma of the lung.
AB  - OBJECTIVE: We hypothesized that clinical outcome of resected early-stage
      adenocarcinoma of the lung can be predicted by the expression of a few critically
      important genes as measured by quantitative real-time reverse-transcriptase
      polymerase chain reaction in formalin-fixed paraffin-embedded primary tumors.
      METHODS: Twenty-two prognostic genes for the metastatic phenotype were identified
      through complementary DNA microarray analysis of 4 cancer cell lines and
      bioinformatics analysis. Expression levels of a subset of these genes (n = 13)
      were measured by real-time time reverse-transcriptase polymerase chain reaction
      in formalin-fixed paraffin-embedded primary adenocarcinoma from patients whose
      disease recurred within 2 years (n = 9) and in patients who did not have a
      recurrence (n = 11). Receiver operating characteristic curves were analyzed to
      establish prognostic values of single genes. The most informative gene was
      combined with the remaining genes to determine whether there was a particular
      pair(s) that yielded high diagnostic accuracy. A small validation study was
      performed. RESULTS: Receiver operating characteristic curve analysis of the
      single genes revealed that high expression of CK19 was associated with
      nonrecurrence (area under the curve = 0.859, confidence interval = 0.651-0.970).
      The CK19/EpCAM2 gene ratio had the most reproducible prognostic accuracy,
      followed by the CK19/P-cadherin ratio. A Kaplan-Meier survival analysis generated
      from the CK19/EpCAM2 ratio resulted in highly significant curves as a function of
      marker positivity (P = .0007; hazard ratio = 10.7). Significance declined but was
      maintained in the validation study. CONCLUSIONS: This preliminary study provides
      evidence that the CK19/EpCAM2 and/or CK19/P-cadherin ratio(s) may be a simple and
      accurate prognostic indicator of clinical outcome in early-stage adenocarcinoma
      of the lung. If further validation studies from large patient cohorts confirm the
      results, adjuvant therapy could be targeted to this high-risk group.

PMID- 18329485
TI  - An objective assessment of the sudomotor response after thoracoscopic
      sympathectomy.
AB  - OBJECTIVE: Thoracoscopic sympathectomy has become an accepted therapeutic option
      for palmar hyperhidrosis. Objective assessment of sweat output after
      sympathectomy, however, has not been reported to date. We report for the first
      time sweat output measurements after sympathectomy during a 3-year postoperative
      period. METHODS: Thoracoscopic sympathectomy was performed by division of T2 and
      T3 sympathetic ganglia in 17 healthy adult patients with no comorbidities.
      Preoperative and postoperative sweat measurements were done at 29 degrees C
      (below sweat threshold, at baseline, after conversation, and after a mental
      arithmetic challenge) and at 40 degrees C (baseline and after exercise) with the
      ventilated capsule technique in left palm, sole, and chest wall. Serial
      postoperative measurements were conducted at 1 and 6 months and 1, 2, and 3
      years. RESULTS: Sweat output fell significantly after sympathectomy relative to
      preoperative levels under all experimental conditions (P < .001, analysis of
      variance) in the left palm. Differences in sweat outputs in the left palm were
      statistically significant between groups at baseline and postoperatively after
      mental arithmetic challenge and exercise at 40 degrees C (P < .05, analysis of
      variance). Compensatory increases in the sweat outputs from the left sole and
      chest were observed after sympathectomy. No patients had recurrence of
      preoperative sweat output values at follow-up. CONCLUSION: According to objective
      sweat output measurements, thoracoscopic sympathectomy results in long-term
      control of palmar hyperhidrosis. This evaluation method is valuable in
      investigating recurrence of symptoms or compensatory hyperhidrosis after
      sympathectomy, providing a robust and objective criterion for planning
      intervention.

PMID- 18329487
TI  - Thoracoscopic lobectomy: report on safety, discharge independence, pain, and
      chemotherapy tolerance.
AB  - OBJECTIVE: Controversies regarding the safety, morbidity, and mortality of
      thoracoscopic lobectomy have prevented the widespread acceptance of the
      procedure. This series analyzed the safety, pain, analgesic use, and discharge
      disposition in patients who underwent thoracoscopic lobectomy and segmentectomy
      at a single institution. METHODS: We collected data from 153 consecutive patients
      who underwent thoracoscopic (video-assisted thoracic surgery) lobectomy and
      assessed the perioperative outcomes, postoperative pain, and chemotherapy course.
      A total of 111 of 127 patients with lung cancer had stage I non-small cell lung
      cancer. The operative technique required 2 ports and an access incision (5-8 cm),
      individual hilar ligation, and lymph node dissection performed without rib
      spreading devices. RESULTS: There were 9 major complications (6%), including 1
      perioperative death (0.7%). Conversion to thoracotomy occurred in 14 patients
      (9.2%). Blood transfusion was required in 11 patients (7%). The median chest tube
      time was 3 days, and the length of hospital stay was 4 days; 94.4% of patients
      went home at the time of discharge, and 5.6% of patients required a
      rehabilitation facility. At a median postsurgical follow-up time of 2 weeks, the
      mean postoperative pain score was 0.6 (0-3), 73% of patients did not use
      narcotics for pain control, and 47% of patients did not use any pain medication.
      Of patients receiving chemotherapy (N = 26), 73% completed a full course on
      schedule and 85% received all intended cycles. CONCLUSION: Thoracoscopic (video
      assisted thoracic surgery) lobectomy can be performed safely. Discharge
      independence and low pain estimates in the early postoperative period suggest
      that this approach may be beneficial. Furthermore, there is a trend toward
      improved tolerance of chemotherapy.

PMID- 18329488
TI  - Utility of detailed preoperative cardiac testing and incidence of post
      thoracotomy myocardial infarction.
AB  - OBJECTIVE: Recent literature has questioned the efficacy of routine detailed
      preoperative cardiac ischemia testing and preoperative cardiac intervention
      before noncardiac surgical procedures. METHODS: We performed a retrospective
      review of patients undergoing thoracotomy (n = 294) between January of 1999 and
      January of 2005. RESULTS: The median age was 62 years. Detailed preoperative
      cardiac testing was performed on 184 patients (63%) and went beyond a thorough
      history, physical examination, and electrocardiogram to include at least one of
      the following: dobutamine stress echo (n = 116), nuclear stress test (n = 66),
      treadmill test (n = 8), and coronary angiogram (n = 40). Evidence for coronary
      disease was detected in 43% of tests (99/230) performed. Revascularization was
      performed in 10% of all patients (4/40) who underwent coronary angiography.
      Postoperative myocardial infarction occurred in 7 patients (2.4%) with 4
      myocardial infarction-related mortalities. No significant difference was found in
      the incidence of myocardial infarction in patients with (n = 184) or without (n =
      110) detailed preoperative cardiac testing (3.3% vs 0.9%, P = .29). Of the 4
      patients (1.4%) who underwent revascularization to treat coronary lesions
      identified during prethoracotomy workup, 2 had a myocardial infarction, 1 of
      which was caused by thrombosis of a coronary stent. In the subset of patients who
      underwent lobectomy (n = 149), detailed cardiac testing was performed on 107
      patients (72%). The incidence of myocardial infarction was similar in tested and
      untested patients (2.8% vs 2.4% respectively, P = 1.0). CONCLUSION: Selective use
      of detailed preoperative cardiac testing refines risk stratification and
      identifies patients for corrective cardiac interventions; however, it did not
      prove fully protective against myocardial infarction after thoracotomy in our
      study.

PMID- 18329489
TI  - Stress-activated protein kinase inhibition to ameliorate lung ischemia
      reperfusion injury.
AB  - OBJECTIVE: Inhibition of cytokines offers modest protection from injury in animal
      models of lung ischemia-reperfusion. Improved strategies would selectively
      inhibit the transcriptional activation response to oxidative stress. Mitogen
      activated protein kinases (p38, c-jun N-terminal kinase, extracellular signal
      regulated kinase) have been shown to be activated after oxidative stress and in
      animal models of acute inflammatory lung injury. We hypothesized that mitogen
      activated protein kinase inhibition would block downstream transcriptional
      activation, providing robust protection from lung ischemia-reperfusion injury.
      METHODS: Experimental rats received inhibitors of p38, c-jun kinase, or
      extracellular signal-regulated kinase before in situ left lung ischemia
      reperfusion. Immunohistochemistry localized cellular sites of mitogen-activated
      protein kinase activation. Several markers of lung injury were assessed. Enzyme
      linked immunosorbent assay measured soluble cytokine and chemokine contents.
      Western blotting assessed mitogen-activated protein kinase phosphorylation.
      Electromobility shift assays measured transcription factor nuclear translocation.
      RESULTS: Immunohistochemistry localized p38 and c-jun kinase activations in
      positive controls to alveolar macrophages. Extracellular signal-regulated kinase
      was activated in endothelial and epithelial cells. Animals treated with p38 or c
      jun kinase inhibitor demonstrated significant reductions in transcription factor
      activation and markers of lung injury. Extracellular signal-regulated kinase
      inhibition was not protective. Western blotting confirmed inhibitor specificity.
      CONCLUSION: Inhibition of p38 and c-jun kinase provided significant protection
      from injury. The alveolar macrophage appears to be the key coordinator of injury
      in response to oxidative stress. Therapeutically targeting specific cell
      population (macrophage) responses to oxidative stress has the potential benefit
      of reducing lung reperfusion injury severity while leaving host immune responses
      intact.

PMID- 18329491
TI  - Successful restoration of function of frozen and thawed isolated rat hearts.
AB  - OBJECTIVE: Long-term organ preservation for transplantation may allow optimal
      donor-recipient matching with potential reduction in the incidence and severity
      of rejection. Complete cessation of metabolism may be obtained by freezing.
      Previous attempts to freeze intact mammalian hearts were limited to -3.6 degrees
      C, restricting tissue ice content to 34%. We hypothesized that our method will
      allow recovery of function of the intact rat heart after freezing to -8 degrees
      C, a temperature at which most of the tissue water is frozen. METHODS: Isolated
      rat hearts were attached to a Langendorff apparatus. After normothermic
      perfusion, cold cardioplegia was induced followed by perfusion with a
      cryoprotecting agent. Hearts were than frozen to -8 degrees C (45 +/- 8 minutes),
      thawed, and reperfused (60 minutes). RESULTS: All frozen and thawed hearts
      regained normal electric activity. At -8 degrees C, ice content was 64.36% +/-
      13%. The use of 10% ethylene glycol for cryoprotection (n = 13) resulted in
      recovery (mean +/- standard deviation) of 49.7% +/- 21.8% of +dP/dt, 48.0% +/-
      23.5% of -dP/dt, 65.2% +/- 30.8% of coronary flow, and 50.4% +/- 23.9% of left
      ventricular developed pressure. Hearts in this group (n = 4) maintained 81.3% +/-
      10% viability compared with 69.3% +/- 14% (not significant) in control hearts
      kept at 0 degrees C for the same duration. Energy stores, represented by
      adenosine triphosphate and phosphocreatine, were depleted to 12.2 +/- 6.1
      micromol/g dry weight and 22.5 +/- 6.4 micromol/g dry weight, respectively,
      compared with 19.0 +/- 2.5 micromol/g dry weight and 36.6 +/- 3.0 micromol/g dry
      weight, respectively (P < .05) in the control hearts. The integrity of muscle
      fibers and intracellular organelles after thawing and reperfusion was
      demonstrated by electron microscopy. CONCLUSION: We demonstrate for the first
      time the feasibility of functional recovery after freezing and thawing of the
      isolated rat heart while maintaining structural integrity and viability.

PMID- 18329492
TI  - Cardiac stem cells in the real world.
AB  - OBJECTIVE: Cardiac stem cell transplantation as a potential means of regenerating
      infarcted myocardium is currently receiving a great deal of interest. However,
      data on these endogenous cardiac precursors are primarily derived from animal
      studies, and their clinical relevance still remains elusive. METHODS: We
      prospectively screened 32 endomyocardial biopsies harvested from heart transplant
      recipients (off rejection episodes) and 18 right appendage biopsies collected
      during coronary artery bypass surgery, and processed the tissue specimens for the
      immunohistochemical detection of markers of stemness (c-kit, MDR-1, Isl-1),
      hematopoietic origin (CD45), mast cells (tryptase), endothelial cells (CD105),
      and cardiac lineage (Nkx2.5). Confocal microscopy was used for colocalization
      experiments. Three right appendage biopsies were also cultured for 2 to 3 weeks,
      at the completion of which c-kit-positive cells were sorted by flow cytometry.
      RESULTS: In endomyocardial biopsies, a median number of 2.7 (1.8-4) c-kit
      positive cells/mm(2) were found, and this number was even significantly smaller
      in right appendage biopsies (1 [0.5-1.8] c-kit-positive cell/mm(2), P = .01). All
      of these c-kit-positive cells co-stained for CD45 and were more specifically
      identified as mast cells by their positive staining for the specific tryptase
      marker. However, none of the c-kit-positive cells expressed the markers of
      stemness MDR-1 and Isl-1 or colocalized with CD105. Flow cytometry confirmed the
      small number of c-kit-positive cells in cultured right atrial appendages.
      CONCLUSION: These data raise a cautionary note on the therapeutic exploitation of
      cardiac stem cells in patients with ischemic cardiomyopathy, who may be the
      elective candidates for regenerative therapy.

PMID- 18329493
TI  - Platelet activation in the postoperative period after lung transplantation.
AB  - OBJECTIVE: During lung transplantation, cells in the pulmonary parenchyma are
      subjected to ischemia, hypothermic storage, and reperfusion injury. Platelets,
      whose granular contents include adhesion receptors, chemokines, and coactivating
      substances that activate inflammatory and coagulant cascades, likely play a
      critical role in the lung allograft response to ischemia and reperfusion. The
      platelet response to the pulmonary allograft, however, has never been studied.
      Here we report significant platelet activation immediately after lung
      transplantation. METHODS: We performed a prospective cohort study comparing
      markers of platelet activation in patients undergoing lung transplantation and
      patients undergoing nontransplant thoracotomy. Plasma levels of soluble P
      selectin, soluble CD40 ligand, and platelet-leukocyte conjugates were measured
      before surgery, after skin closure, and at 6 postoperative hours. RESULTS: Both
      soluble P-selectin and soluble CD40 ligand levels increased significantly after
      lung transplantation but not after thoracotomy. Additionally, platelet-monocyte
      conjugate fluorescence was significantly higher after lung transplantation than
      after thoracotomy alone. CONCLUSION: These findings suggest that platelet
      activation is significantly increased after lung transplantation beyond that
      expected from the postoperative state. The increase in circulating platelet
      monocyte conjugates suggests an important interaction between platelets and
      inflammatory cells. Further research should examine whether platelet activation
      affects early graft function after lung transplantation.

PMID- 18329494
TI  - High-dose aprotinin effectively reduces blood loss during on-pump coronary artery
      bypass grafting with bivalirudin anticoagulation.

PMID- 18329495
TI  - Hemothorax caused by rupture of a primitive thoracic leiomyosarcoma of the
      thoracic aorta: description of a case and literature review.

PMID- 18329496
TI  - Acquired right-to-left shunt through an atrial septal perforation with cyanosis
      after percutaneous transvenous mitral commissurotomy.

PMID- 18329497
TI  - Successful lysis of an aortic prosthetic valve thrombosis with a dosing regimen
      for peripheral artery and bypass graft occlusions.

PMID- 18329498
TI  - Arterial coronary revascularization failure as a result of coronary vasospasm.

PMID- 18329499
TI  - Complete occlusion of the left main coronary artery ostium in Takayasu arteritis.

PMID- 18329500
TI  - Anomalous left coronary artery from the pulmonary artery with an intramural
      course within the aortic wall: report of 3 surgical cases.

PMID- 18329501
TI  - Retrograde aortic perfusion dislodges a dislodged Amplatzer device.

PMID- 18329502
TI  - Thoracic endovascular aortic repair of adult patent ductus arteriosus with
      pulmonary hypertension.

PMID- 18329503
TI  - A modified infarct exclusion technique: triple-patch technique for postinfarction
      ventricular septal perforation.

PMID- 18329504
TI  - Visualization of bronchoalveolar fistula as the presenting sign of lung cancer.

PMID- 18329505
TI  - Incidence of venous thromboembolism in patients undergoing thoracotomy for lung
      cancer.

PMID- 18329506
TI  - Closure of a large tracheoesophageal fistula using AlloDerm.

PMID- 18329507
TI  - End-to-side bronchial anastomosis using the continuous suture technique.

PMID- 18329508
TI  - Thrombus in the left superior pulmonary vein after left upper pulmonary
      lobectomy.

PMID- 18329509
TI  - The role of propensity scores should be discouraged when there is too little and
      too early of new surgical techniques.

PMID- 18329512
TI  - The safety of moderate hypothermic circulatory arrest with selective cerebral
      perfusion.

PMID- 18329513
TI  - Circulatory support system as a bridge to decision in patients with refractory
      acute cardiogenic shock: is there a space for extracorporeal membrane
      oxygenation?

PMID- 18329516
TI  - Mortality associated with pneumonectomy after induction chemoradiation versus
      chemotherapy alone in stage IIIA-N2 non-small cell lung cancer.

PMID- 18329517
TI  - Letter from the editor: heart facts for women.

PMID- 18329518
TI  - Letter from the guest editor: cardiac computed tomography.

PMID- 18329519
TI  - Case of the season: bladder diverticulum.

PMID- 18329520
TI  - Cardiac computed tomography: technique and optimization of protocols.

PMID- 18329521
TI  - Normal and anomalous anatomy of the coronary arteries.

PMID- 18329522
TI  - Approach to analyzing and reporting coronary computed tomography.

PMID- 18329523
TI  - Computed tomography of coronary artery disease.

PMID- 18329524
TI  - Multidetector computed tomography in the evaluation of chest pain in the
      emergency department.

PMID- 18329525
TI  - Evaluation of cardiac function and valves by multidetector row computed
      tomography.

PMID- 18329526
TI  - Computed tomography imaging of left atrium and pulmonary veins for radiofrequency
      ablation of atrial fibrillation.

PMID- 18329528
TI  - Systemic sclerosis (scleroderma) is unique among our rheumatic diseases. Preface.

PMID- 18329529
TI  - The many faces of scleroderma.
AB  - Scleroderma autoantibodies are associated with very specific demographic,
      clinical, organ system, and survival features. The use of scleroderma
      autoantibodies may be very helpful in determining the prognosis, as well as
      monitoring and treatment of scleroderma patients. There are many faces of
      scleroderma that seem to be closely associated with scleroderma autoantibodies.
      These antibodies should be used in performing clinical trials and in doing
      genetic and basic research. Hopefully, these scleroderma antibodies will lead to
      a better understanding of the pathogenesis of scleroderma.

PMID- 18329530
TI  - Genetics and genomic studies in scleroderma (systemic sclerosis).
AB  - It currently is believed that scleroderma is a complex polygenic disease that
      occurs in genetically predisposed individuals who have encountered specific
      environment exposures and/or other stochastic factors. The nature of these
      genetic determinants and how they interact with environmental factors are areas
      of active investigation. This article discusses the evidence that supports a
      strong genetic link to scleroderma. These studies implicate potential
      pathogenetic mechanisms involved in scleroderma, which, it is hoped, may
      translate into clinical utility, including determination of disease risk,
      diagnosis, prognosis, and novel therapeutics.

PMID- 18329531
TI  - The pathology of scleroderma vascular disease.
AB  - Systemic sclerosis is characterized by three distinct pathologic processes:
      fibrosis, cellular/humoral autoimmunity, and specific vascular changes. Although
      a mild vasculitis may sometimes be present, the vascular pathology of scleroderma
      is not necessarily inflammatory and is best characterized as a vasculopathy. In
      this article, the authors propose that SSc vasculopathy is the result of an early
      event involving vascular injury that eventuates in a vicious cycle mediated in
      part by the immune process. The subsequent vascular malformation and rarefaction
      may be a function of systemic angiogenic dysregulation, with over expression of
      vascular endothelial growth factor but a lack of proper interactions with smooth
      muscle cells needed to stabilize and organize blood vessels.

PMID- 18329532
TI  - Vascular disease in scleroderma: mechanisms of vascular injury.
AB  - Vascular endothelial injury in systemic sclerosis (SSc) includes a spectrum of
      changes that involve predominantly the microcirculation and arterioles. The
      pathologic changes in the blood vessels adversely impact the physiology of many
      organ systems, with a reduction in the size of microvascular beds leading to
      decreased organ blood flow and ultimately to a state of chronic ischemia. Current
      hypotheses in SSc vascular disease suggest a possible chemical or infectious
      trigger.

PMID- 18329533
TI  - Vascular disease in scleroderma: angiogenesis and vascular repair.
AB  - Vascular abnormalities are one of the primary pathologic components of
      scleroderma. An early vascular indicator is aberrant nail fold capillaries that
      appear to undergo a switch from a pro- to anti-angiogenic process. Later in the
      disease process, ineffective and aberrant wound healing becomes apparent with
      frequent and widespread fibrosis. Pulmonary hypertension, largely due to the loss
      of pulmonary arterial vasculature, is frequently observed in late stages of the
      disease. The common theme of all these processes is abnormal regeneration of the
      vasculature and ongoing vascular losses due to defective maintenance of the
      vasculature. Although most aspects of vascular injury in scleroderma are poorly
      understood, certain biologic themes are beginning to emerge that are important in
      understanding scleroderma-related vascular disease.

PMID- 18329534
TI  - Regulation of vascular reactivity in scleroderma: new insights into Raynaud's
      phenomenon.
AB  - Because of the role of the RhoA/Rho kinase (ROCK) pathway in regulating numerous
      pathologic processes including vasoconstriction, vascular remodeling, and
      fibrosis, ROCK inhibitors may be especially beneficial in treating Raynaud's
      phenomenon and scleroderma.

PMID- 18329535
TI  - Diagnosis and management of scleroderma peripheral vascular disease.
AB  - The manifestations of peripheral vascular disease in patients who have systemic
      sclerosis (SSc) range from episodic Raynaud's phenomenon to irreversible tissue
      injury with ulceration and gangrene. Structural and functional changes may occur
      in the microvessels, digital arteries, and sometimes more proximal vessels. This
      article discusses the assessment of patients who have Raynaud's phenomenon in
      whom an underlying scleroderma-spectrum disorder is suspected and patients who
      have SSc with critical digital ischemia/ulceration. Different imaging techniques,
      including capillaroscopy and angiography, complement the history and examination,
      and developments in vascular imaging should facilitate future studies of
      pathogenesis and treatment response. New vasoactive treatments are currently
      being researched and older treatments revisited; therefore new approaches to
      therapy will likely be developed over the next 5 to 10 years.

PMID- 18329536
TI  - Fibrosis in systemic sclerosis.
AB  - This article reviews current understanding of the pathophysiology of fibrosis in
      systemic sclerosis. It highlights recent discoveries, insights, and emerging
      research, and potential opportunities for the development of targeted
      antifibrotic therapies.

PMID- 18329537
TI  - Novel treatment approaches to fibrosis in scleroderma.
AB  - The molecular mechanisms leading to tissue fibrosis were only poorly understood
      in the past, and even today the cause or trigger of systemic sclerosis is still
      unknown. Remarkable breakthrough findings have been obtained regarding the
      identification of key molecules, key cellular mechanisms, and key intracellular
      signaling cascades, which mediate the perpetuation of fibrosis rather than
      trigger it. These findings have true translational implications, because
      modifiers of these key mediators and key mechanisms are often in clinical use in
      other disease indications, such as cancer. This article summarizes the clinical
      and preclinical evidence of examples of these novel antifibrotic treatment
      approaches in systemic sclerosis, including stem cell transplantation, modifiers
      of transforming growth factor-beta1 signaling, intravenous immunoglobulins,
      tyrosine kinase inhibitors, and histone deacetylase inhibitors.

PMID- 18329538
TI  - Current approaches to the management of early active diffuse scleroderma skin
      disease.
AB  - Skin sclerosis is a clinical hallmark of systemic sclerosis (SSc) and provides a
      means to classify and evaluate patients. In the diffuse cutaneous subset, skin
      involvement is often extensive and warrants direct therapy. Currently, broad
      spectrum immunosuppressive strategies are used, but more targeted specific
      approaches are now emerging. This article reviews the evidence for efficacy of
      current treatment approaches and future developments for managing skin disease in
      early diffuse cutaneous SSc.

PMID- 18329539
TI  - The heart in scleroderma.
AB  - The heart is one of the major organs involved in scleroderma, the involvement of
      which can be manifested by myocardial disease, conduction system abnormalities,
      arrhythmias, or pericardial disease. Additionally, scleroderma renal crisis and
      pulmonary hypertension lead to significant cardiac dysfunction secondary to
      damage in the kidney and lung. This article summarizes the types and mechanism of
      abnormalities in the heart in scleroderma. The concept of cardiac dysfunction in
      scleroderma and other rheumatologic conditions has received new interest with the
      advent of newer noninvasive imaging techniques, as well as the interest in
      detecting subclinical disease. With this increased interest in cardiac
      manifestations in scleroderma comes the realization that long-term studies are
      needed to better assess the appropriate screening and treatment in this patient
      population.

PMID- 18329540
TI  - Treatment of pulmonary arterial hypertension due to scleroderma: challenges for
      the future.
AB  - Although progress has been made in treatment of pulmonary arterial hypertension,
      serious challenges remain. This article provides an overview of the challenges
      faced in treatment of PAH caused by scleroderma. It also provides a glimpse into
      the future, based on recent developments in the field that hold promise for
      enhancing the treatment of this disease.

PMID- 18329542
TI  - Often forgotten manifestations of systemic sclerosis.
AB  - Many clinical manifestations of systemic sclerosis (scleroderma) often go
      unrecognized; yet they can cause significant morbidity and are challenging to
      manage. This article discusses osteolysis, avascular necrosis of the wrist, oral
      manifestations, erectile dysfunction, pharyngeal weakness, fecal incontinence,
      nonscleroderma renal disease, liver disease, thyroid disease, and neurological
      disease in the scleroderma patient.

PMID- 18329541
TI  - Scleroderma-like fibrosing disorders.
AB  - Many conditions presenting with clinical hard skin and tissue fibrosis can be
      confused with systemic sclerosis (scleroderma). These disorders have very diverse
      etiologies and often an unclear pathogenetic mechanism. Distinct clinical
      characteristics, skin histology, and disease associations may allow one to
      distinguish these conditions from scleroderma and from each other. A prompt
      diagnosis is important to spare patients from ineffective treatments and
      inadequate management. This article highlights nephrogenic systemic fibrosis
      (nephrogenic fibrosing dermopathy), eosinophilic fasciitis (Shulman's syndrome),
      scleromyxedema, and scleredema. These often are detected in the primary care
      setting and referred to rheumatologists for further evaluation. Rheumatologists
      must be able to promptly recognize them to provide valuable prognostic
      information and appropriate treatment options for affected patients.

PMID- 18329543
TI  - Systemic sclerosis and localized scleroderma in childhood.
AB  - Juvenile scleroderma syndromes, including the systemic and the localized
      varieties, represent the third most frequent chronic rheumatic conditions in
      pediatric rheumatology practice. In children, systemic sclerosis shows a
      significantly less frequent involvement of all organs, a higher prevalence of
      arthritis and myositis, and a better outcome than in adults. Recently, new
      classification criteria were proposed, which help improve patient care by
      enabling earlier, more definite diagnoses and by standardizing the conduct of
      clinical trials. Localized scleroderma is the more frequent subtype of
      scleroderma in childhood. It comprises a group of distinct conditions that
      involve mainly the skin and subcutaneous tissues. They range from small plaques
      of fibrosis involving only the skin to diseases causing significant functional
      deformity with various extracutaneous features.

PMID- 18329545
TI  - Slow alpha variant during REM sleep.
AB  - REM sleep resembles wakefulness or drowsiness. The pattern can be low-voltage, or
      else alpha-like. Alpha frequencies are present only during the tonic phases of
      REM sleep and, compared to wakefulness tracings, alpha activities are slightly
      slower by 1-2 Hz and are more monomorphic. The slow alpha-variant rhythm or
      subharmonic alpha pattern consists of rhythmic notched theta waves. It shares the
      same topography and reactivity with the alpha rhythm. We report its presence
      during the tonic phases of REM sleep without any modification in its morphology
      in the first case. In the second case, its morphology was similar to awakening
      but with slower amplitude. No alpha frequencies were found in REM sleep but only
      its slow alpha variant. This study provides evidence that REM sleep is a stage of
      sleep that contains rhythms similar to those seen during wakefulness and
      drowsiness.

PMID- 18329546
TI  - Multichannel recording of median nerve somatosensory evoked potentials.
AB  - OBJECTIVES: Clinical applications of multichannel (>or=64 electrodes)
      electroencephalography (EEG) have been limited so far. Amplitude variability of
      evoked potentials in healthy subjects is large, which limits their diagnostic
      applicability. This amplitude variability may be partially due to spatial
      undersampling of anatomical variations in cortical generators. In the present
      study, we therefore investigated whether 128-channel recordings of somatosensory
      evoked potentials (SEPs) can reduce this amplitude variability in healthy
      subjects. Additionally, we explored the relation between amplitude and age.
      METHODS: We recorded median nerve SEPs using a 128-channel EEG system in 50
      healthy subjects (20-70 years) and compared N20, P27, and P45 amplitude as
      obtained with a 128-channel analysis method - based on butterfly plots and
      spatial topographies - and as obtained using a conventional one-cortical-channel
      configuration and analysis. Scalp and earlobe references were compared. RESULTS:
      Although amplitude variability itself was not reduced, a reduced coefficient of
      variation was obtained with the 128-channel method due to higher SEP amplitudes,
      compared to the conventional one-channel method, independent of reference.
      CONCLUSION: These results suggest that at the cost of some additional preparation
      time, the 128-channel method can measure SEP amplitude more accurately and might
      therefore be more sensitive to physiological and pathological changes. For
      optimal amplitude estimation, we recommend to increase the number of
      centroparietal electrodes or, preferably, to perform at least a 64-channel
      recording.

PMID- 18329547
TI  - Lateralisation of intranasal trigeminal chemosensory event-related potentials.
AB  - AIM OF THE STUDY: To determine whether or not chemosensory event-related brain
      potentials (CSERP) elicited by nociceptive unilateral intranasal (CO2) trigeminal
      stimulation are lateralized and, if they are, whether this hemispheric
      lateralization is related to the side of the stimulated nostril. METHODS: Nine
      healthy right-handed subjects participated to the study. CSERPs were recorded
      after left or right monorhinal CO2 stimulation. Latency and baseline-to-peak
      amplitude of each CSERP component were compared across stimulation conditions
      (left and right nostril), scalp locations (lower-frontal, frontal, mid-temporal,
      central, posterior-temporal, parietal) and hemispheres (left or right), using a
      three-factor analysis of variance (ANOVA) for repeated measures. RESULTS:
      Intranasal trigeminal CO2 stimulation elicited a large N400-P550 complex. This
      complex was preceded by an earlier N300 component. Whatever the stimulated
      nostril, N300, N400 and P550 amplitudes were significantly higher on the right as
      compared to the left hemisphere, at lower-frontal recording sites. The side of
      chemosensory stimulation (left or right nostril) did not significantly affect
      CSERP components. CONCLUSIONS: This study showed that in healthy right-handed
      volunteers with normal olfactory ability, intranasal chemosensory trigeminal
      stimulation may elicit a series of event-related brain potentials, which all
      display a significant right-hemisphere predominance, irrespective of the
      stimulated nostril. The observed lateralization was maximal at lower-frontal
      recording sites.

PMID- 18329548
TI  - Stimulus-response curve of human motor nerves: multicenter assessment of various
      indexes.
AB  - The value of various indexes to characterize the stimulus-response curve of human
      motor nerves was assessed in 40 healthy subjects recruited from four European
      centers of investigation (Creteil, Lausanne, Liege, Marseille). Stimulus-response
      curves were established by stimulating the right median and ulnar motor nerves at
      the wrist, with stimulus durations of 0.05 and 0.5 ms. The following parameters
      were studied: the threshold intensity of stimulation to obtain 10% (I 10), 50% (I
      50), and 90% (I 90) of the maximal compound muscle action potential, the ratios I
      10/I 50, I 90/I 50, (I 90 - I 10)/I 10, (I 90-I 50)/I 50, and (I 50 - I 10)/I 10,
      and the slopes of the stimulus-response curves with or without normalization to I
      50. For each parameter, within-center variability and reproducibility (in a test
      retest study) were assessed and between-center comparisons were made. For most of
      the parameters, the results varied significantly within and between the centers.
      Within the centers, only the ratios I 10/I 50 and I 90/I 50 were found constant
      and reproducible. Between the centers, the absolute intensity thresholds (I 10, I
      50, I 90) and the ratio I 90/I 50 did not show significant differences at
      stimulus duration of 0.5 ms, whatever the stimulated nerve. The reduced
      variability and good reproducibility of the ratios I 10/I 50 and I 90/I 50 open
      perspectives in neurophysiological practice for the use of these indexes of the
      stimulus-response curve, a rapid and noninvasive test.

PMID- 18329549
TI  - Effect of sacral-root stimulation on the motor cortex in patients with idiopathic
      overactive bladder syndrome.
AB  - AIMS OF THE STUDY: It is presumed that idiopathic overactive bladder syndrome
      (OBS) is due to visceral hypersensitivity. Sacral-root stimulation can restore
      the bladder function, but its mechanism remains uncertain. It is well-known that
      long-term peripheral stimulation can induce brain plasticity. Hence, we
      investigated whether brain reorganization occurred along with clinical
      improvement after sacral-root stimulation. MATERIAL AND METHODS: Because toe
      flexion is the index for monitoring wire placement, we used the flexor hallucis
      brevis (FHB) as the target muscle. Transcranial magnetic stimulation (TMS) was
      applied to study motor cortex excitability and the brain mapping of the muscle.
      RESULTS: Six patients with idiopathic OBS were included in the study. All
      demonstrated clinical improvement after sacral-root stimulation. Motor cortex
      excitability and the area of representation for the flexor hallucis brevis muscle
      increased for at least 30 min after sacral-root stimulation had terminated.
      CONCLUSION: Our results showed that cerebral activities changed after sacral-root
      stimulation. The improvement in urinary urgency and urgency perception was
      probably due in part to brain reorganization.

PMID- 18329550
TI  - Histomorphometric analysis of intramyocardial vessels in primary and senile
      amyloidosis: epicardium versus endocardium.
AB  - BACKGROUND: The literature is unclear as to the frequency and degree of vascular
      involvement among the various types of cardiac amyloidosis, specifically the
      senile type. METHODS: We analyzed the intramyocardial vascular involvement, both
      qualitatively and quantitatively, in 18 patients with autopsy-proven cardiac
      amyloidosis [11 with primary amyloidosis (AL) and 7 with senile systemic
      amyloidosis (SSA)]. RESULTS: AL patients (10/11) showed focally transmural
      vascular involvement by amyloid with thickening of the wall and impingement on
      the lumens. In SSA patients (6/7), the amyloid deposition was concentrated
      largely in the adventitia and external media. Histomorphometric analysis revealed
      that all patients with AL, SSA, and heart failure without amyloidosis had greater
      luminal areas than normal controls. In addition, the median of the ratio of
      subendocardial to subepicardial vascular luminal areas was 0.59 in AL patients,
      1.17 in SSA patients, 0.94 in heart failure without amyloidosis patients, and
      0.89 in normal controls (P=.034). CONCLUSIONS: This study shows that the degree
      of vascular involvement and wall thickening with subsequent impingement on the
      lumen is much greater in AL than in SSA. All patients with heart failure, with
      and without amyloidosis, displayed greater luminal areas than normal controls.
      Moreover, a twofold dilatation of the vessels in the subepicardium compared to
      those in the subendocardium was noted only in patients with AL. This may be due
      to transmural vascular involvement by amyloid in these patients, which
      concomitantly decreases the transmural ventricular perfusion pressure, leading to
      compensatory expansion of the subepicardial vessels.

PMID- 18329551
TI  - Transgenic model of smooth muscle cell cycle reentry: expression pattern of the
      collageneous matrix.
AB  - BACKGROUND: We have previously shown that genetically induced smooth muscle cell
      (SMC) cycle reentry in transgenic mouse models expressing the SV40 T antigen
      (TAg) resulted in adaptive arterial remodeling. The present investigation
      targeted the in vitro expression pattern of the collageneous matrix associated
      with TAg-induced SMC cycle modulation. METHODS: SMC cultures were established
      from the transgenic model expressing temperature-sensitive TAg. This allowed
      inducible transgene expression at the permissive temperature of 33 degrees C
      compared with the restrictive temperature of 39.5 degrees C. To distinguish a
      transgene effect from a temperature effect, SMCs with constitutively expressed
      TAg were used as controls. Data were obtained using array technology, Northern
      blotting, reverse transcription polymerase chain reaction, and zymography.
      RESULTS: TAg-induced SMC cycle reentry resulted in significant down-regulation of
      matrix metalloproteinase (MMP)-3, whereas MMP-2, -9, and -11 were not influenced.
      In addition, SMC cycle reentry resulted in significantly increased RNA levels of
      procollagen alpha2(IV), procollagen alpha2(V), and procollagen alpha1(XI),
      whereas procollagen alpha1(III) and procollagen alpha1(VIII) were down-regulated.
      Studies of the RNA expression levels of granulocyte-macrophage colony-stimulating
      factor revealed an up-regulation of this proinflammatory and matrix-modulating
      cytokine. CONCLUSIONS: This transgenic model provides evidence that TAg-induced
      cell cycle reentry is associated with a complex modulation of the collageneous
      matrix. Factors identified in this in vitro study reveal a comprehensive
      expression pattern of candidates, which might allow the vessel to undergo
      adaptive arterial remodeling under in vivo conditions. Our results will give rise
      to further investigations to elaborate on this hypothesis and to improve
      understanding of the role of such factors in vascular diseases.

PMID- 18329552
TI  - Activation of STAT1 transcription factor precedes up-regulation of coxsackievirus
      adenovirus receptor during viral myocarditis.
AB  - The coxsackievirus-adenovirus receptor (CAR) was originally described as a
      transmembrane protein involved in viral infection and was later found to be
      required for normal heart development. However, the role of CAR in virus-induced
      myocarditis has not been investigated so far. The purpose of this study was to
      assess myocardial CAR expression in response to cytokine-induced inflammatory
      reactions during the course of coxsackievirus-induced myocarditis. In Balb/c mice
      intraperitoneally infected with either 2x10(4) plaque-forming units (PFUs) of
      coxsackie B3 virus (CVB3) or 10(2) PFUs CVB3, CAR expression and tyrosine
      phosphorylation of signal transducer and activator of transcription 1 (STAT1), a
      known cytokine-inducible transcription factor involved in viral defense, were
      determined. Our results demonstrated that within the first 7 days after virus
      inoculation, when the viral replication and STAT1 activation in the heart tissue
      was most prominent, the expression of CAR did not surpass that of uninfected
      controls. However, the up-regulation of CAR was observed 9 weeks later, when
      enteroviral RNA was no longer detectable and activation of STAT1 had already
      ceased. In contrast to the STAT1 target genes Mig and Irf1, interferon gamma
      stimulation failed to up-regulate Car expression in isolated cardiomyocytes. In
      human endomyocardial biopsies, Car expression was found to be elevated in
      approximately one third of patients with dilated cardiomyopathy (9 of 30
      patients) as compared with controls. Thus, activation of STAT1 clearly precedes
      the enhanced CAR expression observed during tissue reorganization, suggesting an
      essential role of STAT1 transcription factors in orchestrating the sequential
      actions involved in adaptive immune response.

PMID- 18329553
TI  - Loss of the PTCH1 gene locus in cardiac fibroma.
AB  - BACKGROUND: Cardiac fibroma (CF) is a rare benign tumor that is poorly
      characterized genetically. CF is more commonly encountered in patients with
      Gorlin syndrome (3%) than the general population. Mutations of the tumor
      suppressor gene PTCH1 are the underlying cause of Gorlin syndrome. METHODS:
      Conventional cytogenetic analysis was performed on a peripheral blood and a CF
      sample from a 2-week-old male. In addition, fluorescence in situ hybridization
      (FISH) studies were performed to assess the copy number of the PTCH1 gene locus
      (9q22.3) on metaphase and interphase cells from these same specimens using yeast
      artificial protein (YAC) probe 891G1 and on representative paraffin-embedded
      tissue sections of two additional CFs (one arising in a 2-month-old female and
      the other in a 13-week-old male). None of the patients had Gorlin syndrome.
      RESULTS: Karyotypically, the following abnormal chromosomal complement was
      detected in the 2-week-old male's CF: 46,XY,del(9)(q22q34)[15]. FISH studies
      revealed homozygous loss of the PTCH1 locus in the cytogenetically analyzed CF
      and in the CF arising in the 13-week-old male. Heterozygous loss of this locus
      was identified in the remaining CF from the 2-month-old female. A mutational
      mechanism other than deletion may be responsible for PTCH1 inactivation on the
      other locus in this latter patient. Conventional cytogenetic and FISH studies of
      the peripheral blood sample from the 2-week-old male were normal. CONCLUSION:
      These data support a tumor suppressor gene role for PTCH1 in nonsyndromic or
      sporadic CFs.

PMID- 18329554
TI  - The effects of stretch on vascular smooth muscle cell phenotype in vitro.
AB  - Vascular smooth muscle cells (VSMC) situated in the tunica media of veins and
      arteries are central to maintaining conduit integrity in the face of mechanical
      forces inherent within the cardiovascular system. The predominant mechanical
      force influencing VSMC structural organisation and signalling is cyclic stretch.
      VSMC phenotype is manipulated by externally applied stretch which regulates the
      activity of their contractile apparatus. Stretch modulates cell shape,
      cytoplasmic organisation, and intracellular processes leading to migration,
      proliferation, or contraction. Drug therapy directed at the components of the
      signalling pathways influenced by stretch may ultimately prevent cardiovascular
      pathology such as myointimal hyperplasia.

PMID- 18329555
TI  - Postmortem confirmation of Lyme carditis with polymerase chain reaction.
AB  - BACKGROUND: Cardiac involvement in Lyme disease is uncommon and typically
      manifests clinically by conduction disturbances. Postmortem identification of
      Borrelia burgdorferi has never been reported in a case of Lyme carditis. METHODS
      AND RESULTS: We describe the case of a 37-year-old Caucasian man with a 1-month
      history of fevers, rash, and malaise who died unexpectedly on the day after he
      underwent medical evaluation. The only clinical cardiac abnormality found was
      that of second-degree atrioventricular block. At autopsy, a diffuse carditis,
      characterized by infiltrates of macrophages, lymphocytes, and eosinophils and
      primarily in an interstitial, endocardial, and perivascular distribution, was
      found. Serologic testing from blood drawn on the day before his death
      demonstrated IgG and IgM antibodies against B. burgdorferi, confirmed by Western
      blot. Postmortem polymerase chain reaction (PCR) performed in myocardial tissue
      amplified B. burgdorferi DNA encoding outer-surface protein A. CONCLUSIONS: Lyme
      carditis should be considered in the differential diagnosis of interstitial
      myocarditis with mixed inflammatory infiltrates. This diagnosis can be confirmed
      by PCR testing.

PMID- 18329556
TI  - Fatal haemorrhage due to extensive fragility of medium- and large-sized arteries
      and veins in a young patient with neurofibromatosis 1.
AB  - BACKGROUND: Neurofibromatosis type 1 (NF1) is one of the most frequently
      inherited diseases. Vascular manifestations have been reported, mostly concerning
      stenosis of the renal artery or spontaneous rupture of single arteries. Also,
      venous aneurysms have been reported. METHODS: We present clinical and
      pathological findings of a young patient with NF1 with lethal bleeding due to
      spontaneous rupture of a lumbal and renal artery. RESULTS: High fragility of
      several arteries as well as veins in the abdominal and pelvic arterial and venous
      system resulted in a destroyed vessel structure caused by invading neurogen
      fibres. CONCLUSIONS: In rare cases, NF1 is associated with a severe systemic
      vasculopathy concerning the arterial and venous vascular system.

PMID- 18329557
TI  - Bilateral internal carotid absence: a case report of a rare congenital anomaly.
AB  - BACKGROUND: Bilateral internal carotid artery agenesis (ICAA) is a rare
      developmental anomaly of unknown etiology that is often associated with
      disruption of adequate perfusion to the central nervous system. Nevertheless,
      some patients remain asymptomatic due to collateral circulation involving the
      communicating arteries of the Circle of Willis. Secondary to the hemodynamical
      stress through the collateral circulation, affected patients are at an increased
      risk of developing subarachnoid hemorrhage and intracranial aneurysms. METHODS
      AND RESULTS: We report an unusual case of a 62-year-old man with bilateral ICAA
      who expired following two asystolic events during minor surgery. CONCLUSION: This
      case emphasizes the plasticity of the cerebral collateral circulation during
      development, to the point of normal cerebral perfusion throughout life with no
      ischemic complications.

PMID- 18329558
TI  - Atherosclerotic oxalosis in coronary arteries.
AB  - BACKGROUND: Systemic oxalosis may be hereditary or acquired. In these cases,
      calcium oxalate deposits have been reported in numerous tissues, including the
      media of arteries. In any category, calcium oxalate deposition has not been
      described within atherosclerotic plaques in any arteries. METHODS: As part of a
      retrospective clinicopathologic study, 80 hearts were obtained from the National
      Neurological AIDS Bank in an effort to study coronary atherosclerosis in patients
      infected with HIV. The population consisted of 66 HIV-positive and 14 HIV
      negative patients with an average age of 47 years; 79% were males. Proximal
      coronary arteries were serially sectioned and processed routinely. Sections were
      studied by hematoxylin and eosin staining and, in selected cases, von Kossa stain
      and alizarin red S under different conditions, including polarized light, to
      allow distinction of calcium phosphate from calcium oxalate. Medical histories,
      autopsy reports, and general autopsy slides were reviewed. RESULTS: In four
      patients (three with AIDS), calcium oxalate crystals were observed within
      atherosclerotic plaques in the coronary arteries. Similar deposits were seen in
      the thyroid gland and other organs but not in the kidneys. None of the patients
      had chronic renal failure. CONCLUSION: The calcium oxalate crystal deposits
      observed in the atherosclerotic plaques in the coronary arteries of these four
      patients are unique in two ways: (a) these deposits have not previously been
      described in atherosclerotic plaques; (b) the patients did not demonstrate any of
      the recognized patterns of oxalosis. We suggest the phrase "atherosclerotic
      oxalosis" to describe this finding.

PMID- 18329559
TI  - Mesothelial/monocytic incidental cardiac excrescence.
AB  - Mesothelial/monocytic incidental cardiac excrescence (MICE) is a very uncommon
      lesion. Diagnosis is incidental and may simulate thrombotic lesions. One of the
      hypotheses with regard to the etiology of this lesion is a previous cardiac
      procedure especially mitral valve repair or commissurotomy. Herein, we describe a
      MICE incidentally found in a patient who underwent mitral valve replacement, as a
      thrombotic lesion on the left atrial auricle. Histopathologic examination
      suggested MICE lesions and immunohistochemical stains confirmed it.

PMID- 18329560
TI  - Evaluation of intratester and intertester reliability of the Constant-Murley
      shoulder assessment.
AB  - This study evaluated the reliability of the Constant-Murley Score. Two testers
      assessed 63 patients twice on the same day using the original publication by
      Constant and Murley. The intratester reliability of the total score was high and
      the differences between the tests were small; 2 of 14 items were unreliable. The
      intertester reliability was high, but there were significant median differences
      of the total score; 12 of 14 items were unreliable. We believe that the
      differences between the testers were due to the brief explanations of test
      components in the original publication. The reliability of the Constant-Murley
      Score could possibly be improved by a better standardization of the assessment
      procedure.

PMID- 18329561
TI  - Histologic changes in the maxillary sinus membrane after sinus membrane elevation
      and the simultaneous insertion of dental implants without the use of grafting
      materials.
AB  - OBJECTIVE: The aim of this study was to evaluate the histologic changes in the
      maxillary sinus membrane after sinus membrane elevation and the simultaneous
      insertion of dental implants without additional grafting material. STUDY DESIGN:
      In 6 mongrel dogs, bilateral edentulated flat alveolar ridges were created in the
      maxilla. After 3 months of healing, an implant was unilaterally placed in the
      maxillary sinus in such a way that it protruded 5 mm into the maxillary sinus
      after sinus membrane elevation. On the opposite side, the maxillary sinus was
      left untreated as a control site. The animals were killed 6 months after surgery.
      The maxillary sinus mucosa was examined using light microscopy and scanning and
      transmission electronic microscopy. RESULTS: There were no morphologic or
      ultrastructural differences in the sinus membrane between groups. CONCLUSION: The
      results indicate that the surgical procedure by which implants are inserted into
      the sinus cavity by elevating the sinus membrane without adding any graft
      material appears to have little influence on the histologic characteristics of
      the sinus membrane.

PMID- 18329562
TI  - Fibrous dysplasia of the mandible: Surgical treatment with platelet-rich plasma
      and a corticocancellous iliac crest graft-report of a case.
AB  - This paper reports on an alternative treatment method for mandibular
      reconstruction in a very rare symptomatic adult form of fibrous dysplasia. The
      treatment included excision of all the dysplastic tissue excluding the inner
      cortex and the lower border of the mandible, where cryosurgery was applied.
      Platelet-rich plasma was added to the autogenous bone and used to fill dead
      spaces and interfaces. Three months after reconstruction, implants were inserted
      in the hard dense bone that showed no resorption. Seven years after surgery, the
      patient was completely asymptomatic and had an excellent cosmetic outcome. A very
      simple method, based on a new paradigm approach, provided excellent functional
      and cosmetic results avoiding complex reconstruction procedures and delayed
      hospitalization in a patient with fibrous dysplasia.

PMID- 18329563
TI  - Effect of propranolol on mepivacaine serum concentrations in dental practice.
AB  - OBJECTIVE: The objective of this study was to determine the effect of propranolol
      pretreatment on mepivacaine serum concentrations in dental patients. STUDY
      DESIGN: In a double blind, randomized, 2-way crossover study, 10 patients
      ingested 30 mg propranolol or placebo, 2 hours before local anesthesia for dental
      scaling. Each subject received a single dose of 51 mg mepivacaine for posterior
      superior alveolar nerve block. Mepivacaine in venous serum was measured for up to
      1 hour, after 5, 15, 30, 45, and 60 minutes from injection. Serum concentrations
      of mepivacaine were determined by gas chromatography. Blood pressure and heart
      rate were measured before and after propranolol or placebo and after each
      sampling. RESULTS: Peak serum concentrations of mepivacaine, C(max) (1.214 +/-
      0.746 microg/mL(-1)), were significantly increased by propranolol (2.249 +/-
      1.559 microg/mL(-1), P < .05). Propranolol pretreatment reduced blood pressure
      and heart rate. CONCLUSION: Although propranolol pretreatment increased almost
      doublefold mepivacaine serum concentrations and reduced blood pressure and heart
      rate, mepivacaine can be used safely in dental patients taking propranolol for
      short-duration interventions.

PMID- 18329564
TI  - Junctional epidermolysis bullosa associated with hypoplastic enamel and pervasive
      failure of tooth eruption: Oral rehabilitation with use of an overdenture.
AB  - This report describes a previously unreported case of generalized hypoplastic
      enamel and failure of eruption of the permanent maxillary teeth and only partial
      eruption of the permanent mandibular teeth in an 18-year-old male diagnosed with
      junctional epidermolysis bullosa. Similar anomalies were reported to have
      affected the deciduous dentition. Beginning at 4 years of age, oral
      rehabilitation has been conservatively managed with the fabrication of various
      maxillary complete overdentures. The use of this prosthesis has provided an
      economical, nonsurgical treatment option when oral soft tissue permits and with
      relative ease of construction.

PMID- 18329565
TI  - Toxic epidermal necrolysis with a rare long-term oral complication requiring
      surgical intervention.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare and potentially fatal
      adverse dermatologic reaction, often secondary to drug intake. METHODS AND
      RESULTS: We report a case of an adult male who developed TEN that was complicated
      by a sepsis-induced coma lasting a period of 3 months. Although the patient
      eventually recovered, severe oral mucosal involvement during the course of
      disease resulted in frenum-like fibrotic bands that connected movable oral mucosa
      (tongue and lips) to attached oral mucosa (gingiva). This complication was
      painful and also affected his ability to speak and maintain adequate oral
      hygiene, requiring surgical intervention to restore structure and function.
      CONCLUSIONS: This oral manifestation in relation to TEN is rarely reported in the
      literature and represents a preventable complication.

PMID- 18329566
TI  - Colloid milium of the oral cavity: a rare presentation.
AB  - Colloid milium (CM) is a rare condition characterized by the presence of multiple
      dome-shaped amber- or flesh-colored papules developing on sun-exposed skin. It is
      a degenerative condition linked to excessive sun exposure and possibly exposure
      to petroleum products and hydroquinone. The origin of the colloid deposition in
      the dermis is uncertain, although it is thought to be due to degeneration of
      elastic fibers. The condition is rare, with only 100 case reports documented in
      the world literature. The most commonly involved sites are the face, periorbital
      region, backs of the hands, back and sides of the neck, and ears. Involvement of
      the oral cavity is extremely rare. The purpose of this article is to report an
      extremely rare first case of CM of the oral cavity and to discuss the clinical,
      pathologic and therapeutic spectra of CM.

PMID- 18329567
TI  - Leiomyomatous hamartoma: report of two cases and review of the literature.
AB  - Two cases of leiomyomatous hamartoma (LH) in patients of Latin ancestry are
      reported here. The first lesion was detected on the incisive papilla of a 19-year
      old woman; this is an unusual age because these lesions are commonly observed
      during the first years of life. The second lesion found on the middle-dorsum of
      the tongue was observed in a 5-month-old boy. The diagnosis was based on the
      histopathological appearance and confirmed by immunohistochemistry with
      positivity for smooth muscle actin, muscle-specific actin, S-100 protein and
      desmin. To date, only 16 cases have been reported in the English-language
      literature. Controversial epidemiological data, histogenesis,
      clinical/histopathological features, and differential diagnosis are discussed
      herein.

PMID- 18329568
TI  - Histologic and histomorphometric analysis of posterior region of the human
      temporomandibular disc.
AB  - OBJECTIVE: The aim of this study was to analyze histologic and histomorphometric
      features of the articular disc in groups with and without disc displacement.
      STUDY DESIGN: A sample of 39 temporomandibular joints TMJs (31 case specimens, 8
      control specimens) from 28 patients (mean age 31.2 years) were recruited for this
      study. The patients were considered to be affected and treated surgically with
      disc repositioning when presenting painful clinical signs of disc displacement
      after unsuccessful nonsurgical treatment for at least 6 months. Of the control
      patients, 4 presented condyle fracture which required opening to be reduced for
      treatment, and 4 displayed active condyle hyperplasia. The posterior region of
      the disc was removed and sent for histologic and histomorphometric analysis.
      Histologic (hematoxylin-eosin) and histomorphometric (picro-Sirius red) analyses
      were performed. Statistically significant differences between the analyzed groups
      were accessed through the chi-squared test (P <or= .05). The Mann-Whitney U test
      was used to observe the differences between mean values when variables did not
      present normal distribution [Kolmogorov-Smirnov(a) test]. RESULTS: There were no
      significant differences between the groups in relation to the parameters studied
      by histologic and histomorphometric analysis (using or not using polarization).
      CONCLUSIONS: To the limits of this study, there were no significant histologic
      and histomorphometric differences in the articular disc between groups with and
      without TMJ dysfunction.

PMID- 18329569
TI  - An unusual case of double teeth with facial and lingual talon cusps.
AB  - Double teeth and talon cusps are rare developmental dental anomalies affecting
      both primary and permanent dentitions. Talon cusps normally occur on the palatal
      surface of permanent maxillary incisors, although double teeth are more common in
      the primary anterior dentition. This paper describes a rare case of fusion of the
      mandibular permanent incisors with labial and lingual talon cusps. An
      understanding of these dental anomalies and their associated problems are
      important to provide prophylactic measures, thereby preventing or minimizing
      possible complications.

PMID- 18329570
TI  - Prevalence in digital panoramic radiographs of carotid area calcification among
      Iraqi individuals with stroke-related disease.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of carotid
      calcification on digital dental panoramic tomography in a group of the Iraqi
      population who have some stroke-related vascular and or metabolic disease. STUDY
      DESIGN: Digital dental panoramic tomographic images of 157 adult patients of age
      range 40-80 years having chronic illnesses such as coronary heart diseases,
      hypertension, type 2 diabetes, and hyperlipidemia and of 43 control subjects (age
      range 40-71 years, free of systemic diseases) were made and examined for the
      presence of carotid artery calcification adjacent or just below the
      intervertebral space between C3, C4, and C5 on both sides of patient's neck. The
      study group was subclassified into vascular, metabolic, and vascular-metabolic
      groups. Determinations were made of the prevalence, number, and distribution of
      carotid area calcifications. Forward stepwise logistic regression analysis was
      used to determine which risk factor is more liable to develop carotid artery area
      calcification. RESULTS: The statistical difference between patients with stroke
      related diseases (vascular, metabolic, and vascular-metabolic groups) versus
      patients in the control group was highly significant concerning the prevalence of
      carotid area calcifications (P < .01). Carotid area calcification was identified
      in 38.8% of the study group. Bilateral calcifications were observed more than
      unilateral calcification for both genders (26.6% vs. 13.9% for men; 24.4% vs.
      12.8% for women). CONCLUSION: People with stroke-related vascular and/or
      metabolic diseases have greater prevalence of calcified area calcifications seen
      on panoramic radiographs than people who are otherwise healthy.

PMID- 18329571
TI  - Endodontic management of a maxillary first molar with two palatal roots and a
      single fused buccal root diagnosed with spiral computed tomography - a case
      report.
AB  - The aim of this case report is to present an endodontically managed maxillary
      first molar with an unusual morphology of 2 palatal roots and a single fused
      buccal root. An accurate assessment of this morphology was made with the help of
      spiral computerized tomography, which revealed that the contralateral tooth also
      had a similar morphology.

PMID- 18329572
TI  - An in vivo comparison of working length determination by only root-ZX apex
      locator versus combining root-ZX apex locator with radiographs using a new
      impression technique.
AB  - OBJECTIVE: The objective of this study was to compare, in vivo, the accuracy of
      working length determination using only the Root-ZX electronic apex locator
      versus adjusting Root-ZX measurements after obtaining a working length
      radiograph. STUDY DESIGN: The working length was determined in 25 premolar root
      canals using Root-ZX and K-files were fixed at these positions. Radiographs were
      acquired and interpreted, and the recorded working length measurement was
      adjusted, if necessary, for a combined measurement. The teeth were then extracted
      in an effort to determine the position of the file tip to the root canal
      constriction. On the basis of the position of the file tip to the apical foramen,
      polyvinylsiloxane impressions of the root apex were taken, or the root was
      imbedded in acrylic resin and ground in order to measure the position of the file
      tip to the apical constriction. RESULTS: The Root-ZX alone detected the apical
      constriction within +/- 0.5 mm in 84% of the samples (21 of 25 canals). However,
      96% (24 of 25 canals) were within this range when the combination of Root-ZX and
      radiographs was used. We noted no statistical significance between these 2
      methods (P > .05). CONCLUSION: Using a Root ZX Electronic Apex Locator combined
      with radiographs is recommended for the determination of working length, although
      there was no statistical significance between those 2 groups in this study.

PMID- 18329573
TI  - Ex vivo study of manual and rotary instrumentation techniques in human primary
      teeth.
AB  - OBJECTIVE: This study aimed to evaluate, ex vivo, time and dentin removal by
      manual and rotary instrumentation in human primary teeth. STUDY DESIGN: Eighty
      primary teeth were divided into 2 groups, embedded in resin, and sectioned for
      evaluation before and after instrumentation. For manual technique, teeth were
      prepared using K-type files and rotary preparation was performed with Hero 642.
      All root canals were prepared up to size 40, and the instrumentation time was
      recorded. Dentin removal was calculated using digital image software. Data was
      statistically analyzed using chi-squared, Mann-Whitney, and t tests. RESULTS:
      Manual instrumentation removed more dentin in all groups compared with rotary
      instrumentation (P < .05). In some specimens, root perforations were observed in
      areas coinciding with largest root resorption. Rotary technique showed the
      shortest instrumentation time (P < .05). CONCLUSIONS: Deciduous teeth, without
      significant root resorption, have enough root structure for instrumentation up to
      size 40. Rotary technique required less time and generated less dentin removal.

PMID- 18329574
TI  - Success rate of Sealapex in root canal treatment for primary teeth: 3-year follow
      up.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical and radiographic
      success of Sealapex pulpectomies in primary teeth. STUDY DESIGN: Root canals of
      62 primary teeth were filled with Sealapex. The tooth was restored with a
      stainless steel crown, amalgam, compomer, or glass ionomer cement. Clinical and
      radiographic evaluations of pulpectomized teeth were performed for up to 36
      months afterward. RESULTS: The overall success rate was 92.3%. During the follow
      up period, 4 teeth (7.7%) showing periapical lesion and pathologic resorption
      were extracted and rated as "failure." There were no statistically significant
      differences between success rate and extent of root canal filling material (P >
      .05). None of the fillings showed complete resorption in the canals. There were
      no significant differences among the restorative materials (P > .05). CONCLUSION:
      Based on the results of this study it can be concluded that Sealapex can be used
      successfully in root canal treatment for primary teeth.

PMID- 18329575
TI  - Cause-related marketing: the uneasy alliance between altruism and corporate
      greed.

PMID- 18329576
TI  - Dentists' scope of professional responsibilities.

PMID- 18329577
TI  - Importance of the randomized controlled trial in providing evidence of treatment
      efficacy.

PMID- 18329578
TI  - Ulcerated midline nodule of the hard palate.

PMID- 18329579
TI  - Association of oral yeast carriage with specific host factors and altered mouth
      sensation.
AB  - OBJECTIVES: The aim of this study was to determine if there was a significant
      association between the presence of altered mouth and taste sensations with oral
      carriage of yeasts and to assess the factors that influence the yeast carriage.
      STUDY DESIGN: The oral and dental status including unstimulated (USFR) and
      stimulated (SSFR) whole salivary flow rates of a total of 509 subjects was
      recorded. Saliva specimens were collected for microbiologic examination. Multiple
      logistic regression analysis was performed to identify any factors that were
      significantly associated with the prevalence of oral yeasts. RESULTS: Old age,
      clinical signs of oral dryness, denture wearing, and a reduction in USFR
      increased the prevalence of yeasts, whereas patient gender, levels of dentition,
      the sensation of dry or burning mouth, taste disorders, and SSFR were not
      associated with increased prevalence of oral yeasts. CONCLUSIONS: An increased
      prevalence of oral yeasts was not found to relate to changes in mouth sensation
      alone. Other factors, most notably patient age, the wearing of dentures, clinical
      signs of oral dryness, and salivary flow rate under rest conditions, were,
      however, found to be closely associated with oral yeast carriage.

PMID- 18329580
TI  - Low-level laser therapy for treatment of temporomandibular joint pain: a double
      blind and placebo-controlled trial.
AB  - OBJECTIVE: The objective of this study was to assess the effectiveness of low
      level laser therapy (LLLT) in the management of temporomandibular joint (TMJ)
      pain in a random and double-blind research design. STUDY DESIGN: TMJ pain
      patients, randomly assigned, received 2 to 3 treatments per week for 8 weeks of
      active LLLT (Helium Neon, 632.8 nm, 30 mW) (n = 26) or sham LLLT (n = 26).
      Measures of TMJ pain during function were evaluated at baseline and weeks 2, 4,
      and 8 after the first laser therapy. RESULTS: At the 8-week point, within-group
      improvements were present for TMJ pain during function, for both the active and
      sham LLLT groups (P = .000). Between-group differences were not highly evident (P
      > .05). CONCLUSION: The study suggests that LLLT is not better than placebo at
      reducing TMJ pain during function.

PMID- 18329581
TI  - Antifungal susceptibility testing of micafungin against Candida glabrata
      isolates.
AB  - OBJECTIVE: Antifungal susceptibility of micafungin against isolates of C.
      glabrata was performed to evaluate the hypothesis that micafungin may be a
      suitable alternative in treating those patients whose infections are from C.
      glabrata and have developed resistance to fluconazole. STUDY DESIGN: A total of
      119 clinical isolates were obtained from the oral cavity of 22 patients with
      oropharyngeal candidiasis or oral colonization with C. glabrata. All strains
      evaluated were from patients who had either HIV infection or were receiving
      radiation therapy for head and neck cancer. Inocula were prepared using Clinical
      Laboratory and Standards Institute (CLSI) M27-A2 guidelines. The plates were
      incubated at 35 degrees C and the minimum inhibitory concentrations (MICs) were
      determined at 24 and 48 hours. RESULTS: Micafungin exhibited good in vitro
      activity against most isolates, including those showing marked resistance to
      fluconazole. CONCLUSION: Micafungin has excellent antifungal effects in vitro
      against C. glabrata isolates and appears to be a good treatment option even
      against those isolates resistant to fluconazole. A clinical trial should be
      performed to confirm these findings.

PMID- 18329582
TI  - Anxiety and salivary cortisol levels in patients with burning mouth syndrome:
      case-control study.
AB  - OBJECTIVE: The objective of this study was to evaluate the anxiety and salivary
      cortisol levels in patients with burning mouth syndrome. STUDY DESIGN: A case
      control ed into 2 groups: BMS, with diagnosis of the syndrome, and control,
      without any complaint of burning mouth. Anamnesis, oral examination, sialometry,
      the application anxiety inventory, and 3 saliva samples for cortisol analysis
      were done in every patient. RESULTS: Statistical difference for subjective
      xerostomia was found on the BMS group (P = .01), but salivary flow rate was
      normal in both groups. BMS group presented higher anxiety (P = .001) and salivary
      cortisol levels (P = .003) when compared with the control group. CONCLUSION:
      Higher anxiety and salivary cortisol levels were positively associated with the
      presence of BMS.

PMID- 18329583
TI  - Use of topical medication in orofacial neuropathic pain: a retrospective study.
AB  - OBJECTIVE: The objective of this study was to evaluate the effect of topical
      medications as a single treatment or in combination with systemic medications in
      the treatment of orofacial neuropathic pain conditions. STUDY DESIGN: A
      retrospective chart review of 39 patients treated for orofacial neuropathic pain
      at the Orofacial Pain Clinic in the New Jersey Dental School was performed. In
      line with the treatment selection, the subjects were divided into 3 groups:
      topical medications only (n = 12), systemic medications only (n = 10), and a
      combination of both (n = 17). RESULTS: The starting pain level as expressed in
      pain Visual Analog Scale for the 3 groups was significantly different. The
      combined treatment group baseline pain level (7.5 +/- 0.403 SEM; P = .0015) and
      the systemic treatment only group pain level (8.6 +/- 0.611 SEM; P = .0375) was
      significantly elevated compared to the topical only group (6.1 +/- 0.716 SEM; P =
      .1057). Following treatment, pain level was significantly reduced in all 3
      groups. The combined group had the highest pain relief (52.0 +/- 6.676 SEM %
      reduction; P < .0001) followed by the systemic-only group (40.6 +/- 9.727 SEM %
      reduction; P = .0029) and the topicals-only group (40.9 +/- 10.775 SEM%
      reduction; P = .0048). The time taken for the topical treatment only to act was
      significantly shorter (3 weeks +/- 0.479 SEM; P = .0015) when compared with the
      systemic-only (4 weeks +/- 0.772 SEM; P = .3629) and the combined group (5.5
      weeks +/- 0.912 SEM; P = .1738). CONCLUSION: Topical medication as single
      treatment or in combination with systemic medications can reduce orofacial
      neuropathic pain severity. Further prospective research should be performed to
      validate this treatment option.

PMID- 18329584
TI  - Lymphadenoma of parotid gland: Two additional cases and a literature review.
AB  - For classification purposes, proper identification of infrequent and unique
      salivary gland tumors requires the gradual accumulation of a sufficient number of
      cases. Lymphadenoma (i.e., an adenomatous, generally parotid-based lesion with an
      exaggerated lymphocytic infiltrate, but a lack of sebaceous differentiation) has
      approximately 9 reported cases. This report adds 2 additional cases occurring as
      a discrete, at least partially encapsulated nodule in the parotid gland. Embedded
      within the extensive lymphocytic component were isolated nests of solid or
      glandular epithelium, with 1 case displaying a few foci of chondrocytic
      differentiation. Immunohistochemical investigation of the latter case revealed
      the presence of both luminal and myoepithelial cells.

PMID- 18329585
TI  - A comparative CT evaluation of pharyngeal airway changes in class III patients
      receiving bimaxillary surgery or mandibular setback surgery.
AB  - OBJECTIVE: The purpose of this study was to compare the morphologic changes of
      the upper airway space in Class III patients who underwent mandibular setback or
      bimaxillary surgery (maxillary advancement and mandibular setback) by computed
      tomography at 2 levels: soft palate and base of tongue. METHODS: The sample
      consisted of 47 subjects in 2 groups who had been diagnosed as having Class III
      skeletal deformities and had been treated by mandibular setback or bimaxillary
      surgery (maxillary advancement and mandibular setback). Anteroposterior, lateral,
      and cross-sectional area dimensions of the airway at the level of soft palate and
      base of tongue were measured pre- and postoperatively on computed tomography
      images. RESULTS: Anteroposterior dimensions of the airway decreased in both
      groups (P < .0001); however, the reduction was significantly less in cases
      treated with bimaxillary surgery (P < .05). In the mandibular setback surgery
      group, the cross-sectional area of the airway decreased significantly (P < .001).
      Although the cross-sectional area of the airway decreased in the bimaxillary
      surgery group, the reduction was not statistically significant (P > .05).
      CONCLUSIONS: This study suggests that bimaxillary surgery can prevent narrowing
      of the upper airway in the correction of Class III deformities in comparison with
      mandibular setback surgery used as the sole treatment. Computed tomography was
      valuable in determining the effects of surgical treatment on pharyngeal airway
      dimensions.

PMID- 18329586
TI  - Gemella morbillorum in primary and secondary/persistent endodontic infections.
AB  - OBJECTIVE: To investigate the presence of Gemella morbillorum by culture or
      nested PCR in primary and secondary/persistent endodontic infections. STUDY
      DESIGN: Microbial samples were taken from 50 cases with primary and 50 cases with
      secondary/persistent endodontic infections. Microbiologic techniques were used
      for culture and identification. The DNA extracted from the samples was analyzed
      for the presence of the target species using species-specific primers. RESULTS:
      Culture and polymerase chain reaction (PCR) identified the species in 23 and 77,
      respectively, of 100 root canals. Culture yielded the test organism in 19 of 50
      (38%) of root canal samples from primary and in 4 of 50 (8%) from
      secondary/persistent infections. PCR yielded the test organisms in 41 of 50 (82%)
      and 36 of 50 (72%) of the, respectively, primary and secondary/persistent root
      canal infections studied. CONCLUSION: Gemella morbillorum was identified more
      frequently in primary endodontic infections than in secondary/persistent ones. A
      higher frequency of the target species was detected by PCR than by culture.

PMID- 18329587
TI  - Observations of biofilm growth on human dentin and potential destruction after
      exposure to antibiotics.
AB  - OBJECTIVES: This study was performed to observe biofilm formation on dentin and
      to then observe effects of clinically achievable antimicrobial drug
      concentrations on these biofilms. STUDY DESIGN: Wild-strain endodontic bacteria
      were anaerobically cultured from necrotic pulps of extracted human teeth and used
      to grow biofilms on sterilized dentin slices in an anaerobic chamber for 12 days.
      Then these biofilms were exposed to ampicillin, doxycycline, clindamycin,
      azithromycin, or metronidazole. Each day for 8 days, specimens were fixed using
      2% glutaraldehyde and examined with a scanning electron microscope (SEM).
      RESULTS: The SEM images revealed the presence of a mature biofilm after 8 days of
      growth and that none of the antibiotics tested was effective in eliminating the
      biofilm even after 8 days of exposure. CONCLUSION: Biofilms are formed in a few
      days and are resistant to antimicrobial drugs.

PMID- 18329588
TI  - Comparison of preparation design and material thickness on microbial leakage
      through Cavit using a tooth model system.
AB  - Few studies have compared Cavit thickness and access design as factors in
      microbial leakage. The present study used an acrylic tooth model to measure
      leakage of Streptococcus mutans. Pilot studies confirming the sterility of Cavit
      showed it will inhibit microbial growth for 2 days. The experiments compared
      class I preparations where Cavit thickness was 4 mm with class II preparations
      where thickness was 2-3 mm. Accesses sealed with cotton pellets were compared
      with those without cotton. Results of the study showed no bacterial contamination
      in any of the class I samples (up to 14 days). Some class II samples showed
      contamination at day 1 (3 out of 14), with all contaminated at day 7 (14 of 14),
      yet only 1 contaminated at day 14 (1 out of 14). The results suggest that a 4-mm
      thickness of Cavit should prevent bacterial ingress for at least 2 weeks, but
      microbial leakage may occur if temporary thickness is less than 3 mm or in a
      complex access preparation.

PMID- 18329589
TI  - Beta-tricalcium phosphate, white mineral trioxide aggregate, white Portland
      cement, ferric sulfate, and formocresol used as pulpotomy agents in primary pig
      teeth.
AB  - OBJECTIVE: The purpose of this study was to evaluate and compare the effects of
      formocresol (FC), ferric sulfate (FS), white mineral trioxide aggregate (WMTA),
      white Portland cement (WPC), and beta-tricalcium phosphate (beta-TCP) on
      pulpotomized primary teeth of pigs. STUDY DESIGN: Fifty teeth of three 3-month
      old pigs were pulpotomized with these materials. Three weeks later, the animals
      were euthanized and the specimens were prepared for histological examination.
      RESULTS: There was no significant difference between beta-TCP, WMTA, and WPC in
      terms of primary pulp response, hard tissue formation, and normal pulp tissue
      preservation. But, both FS and FC irritated the pulp tissue, provoking a more
      inflammatory pulp response than beta-TCP, WMTA, and WPC. CONCLUSION: Beta-TCP,
      WMTA, and WPC are histologically more effective pulpotomy agents than formocresol
      and ferric sulfate in primary pig teeth.

PMID- 18329590
TI  - Antidepressants in short-term treatment of binge eating disorder: systematic
      review and meta-analysis.
AB  - OBJECTIVE: To evaluate the effects of antidepressant interventions for patients
      with Binge Eating Disorder (BED). METHOD: A systematic review and meta-analysis
      of available randomized controlled trials including a quality appraisal was
      conducted. Six databases: PUBMED, EMBASE, PSYINFO, LILACS, The Cochrane
      Collaboration Controlled Trials Register and The Cochrane Depression, Anxiety and
      Neurosis Group Database of Trials were searched using an electronic search
      strategy. Articles published during the period from January 1994 to December 2005
      were included. RESULTS: From the 3357 articles initially identified, 19 full
      manuscripts were selected and analyzed and 7 studies fulfilled the inclusion
      criteria and were included in the final analysis. Data from the meta-analysis
      revealed that binge-eating remission rates were higher in patients receiving
      antidepressants when compared with placebo. No difference in body weight has been
      found as measured by short-term change in body mass index. Most studies were
      short-term trials (median duration: 8 weeks). The only 16-week duration study did
      not show superiority of antidepressants over placebo. CONCLUSION: Available data
      are not sufficient to formally recommend antidepressants as a single first line
      therapy for both short-term remission of binge-eating episodes and weight
      reduction in patients with BED. BED is a chronic condition and very short-term
      studies (8 weeks) may be of limited value.

PMID- 18329591
TI  - Perceived stress and eating behaviors in a community-based sample of African
      Americans.
AB  - Previous studies have reported that psychological stress is associated with
      greater food consumption, particularly consumption of high fat foods. We are
      unaware of any studies that have examined stress-induced eating among African
      Americans (AAs). The goals of the current study were to examine the relationship
      between perceived stress and high fat eating behaviors in a sample of AAs, to
      examine whether this relationship is stronger among overweight and obese
      participants, and to examine whether haphazard meal planning mediates the
      relationship between perceived stress and high fat eating behaviors. One hundred
      fifty-nine adults from a metropolitan area completed the Perceived Stress Scale
      (PSS-10), the Eating Behaviors Pattern Questionnaire (EBPQ), a demographic
      questionnaire, and body mass was assessed with BMI. Perceived stress was
      associated with haphazard planning and emotional eating, but not related to other
      high fat eating domains in the overall sample. These findings held for overweight
      and obese participants with the addition of snacking on sweets. High fat eating
      behaviors were not mediated by haphazard meal planning. These findings are
      consistent with other studies which demonstrate a link between stress and eating.
      Long-term interventions for high fat consumption and obesity should include an
      examination of perceived stress among AAs.

PMID- 18329592
TI  - The Eating Disorder Recovery Self-Efficacy Questionnaire (EDRSQ): change with
      treatment and prediction of outcome.
AB  - The purpose of this study was to examine the predictive validity of the Eating
      Disorder Recovery Self-Efficacy Questionnaire (EDRSQ), an empirically-derived
      self-report instrument that assesses confidence to eat without engaging in eating
      disordered behavior or experiencing undue emotional distress (Normative Eating
      Self-Efficacy) and confidence to maintain a realistic body image that is not
      dominated by pursuit of thinness (Body Image Self-Efficacy). Participants were
      104 female inpatients with anorexia nervosa (AN), subthreshold AN, or underweight
      bulimia nervosa who were treated at a specialized eating disorder clinic and
      completed the EDRSQ and Eating Disorder Inventory-2 (EDI-2) Drive for Thinness
      (DT) and Body Dissatisfaction (BD) subscales upon admission. A subset of patients
      completed the EDRSQ (n=81) and EDI-2 subscales (n=70) following inpatient
      treatment. Self-efficacy increased significantly during treatment. EDRSQ scores
      at admission were inversely related to length of hospital stay and posttreatment
      DT and BD subscales and positively related to partial hospital weight gain rate.
      The EDRSQ significantly predicted length of hospital stay and posttreatment BD
      above and beyond clinical indicators and eating disorder psychopathology at
      inpatient admission. Findings support the validity of the EDRSQ and suggest it is
      a useful predictor of short-term hospital treatment outcome in underweight eating
      disorder patients.

PMID- 18329593
TI  - The reliability and validity of the dichotomous thinking in eating disorders
      scale.
AB  - The Dichotomous Thinking in Eating Disorders Scale (DTEDS) is a short, self
      report measure that can be used to assess the presence of a rigid, "black-and
      white" cognitive thinking style. It was originally developed for use in a study
      of psychological predictors of weight regain in obesity. The DTEDS consists of
      two subscales. Items on the Eating subscale assess dichotomous thinking with
      regards to eating, dieting or weight, and items on the General subscale assess
      dichotomous thinking more generally. This study aimed to examine the factor
      structure and psychometric properties of the DTEDS in a sample of treatment
      seeking eating disordered (N=87) and overweight/obese (N=111) women. Confirmatory
      factor analysis demonstrated that a two-factor model provided a better fit to the
      data than a one-factor model. The psychometric properties of the final scale were
      excellent, with evidence being provided for the reliability and validity of the
      two subscales. Overall, the results indicated that the DTEDS is a reliable
      instrument that can be used to assess eating-specific as well as more general
      aspects of dichotomous thinking.

PMID- 18329594
TI  - Body checking in the eating disorders: association with narcissistic
      characteristics.
AB  - There is substantial evidence that body image is a clinically important element
      of eating pathology, and that patients' body checking cognitions and behaviours
      are key elements in the maintenance of that body image. However, there is little
      understanding of individual differences in body checking. This study considered
      the potential role of narcissism and narcissistic defences in driving body
      checking cognitions and behaviours. 68 eating-disordered and 70 non-clinical
      women completed well-validated measures of body checking and narcissism. There
      were specific patterns of association between different elements of narcissism
      and different aspects of body checking. These patterns are compatible with a
      model where body checking serves the defensive function of maintaining self
      esteem, rather than promoting positive levels of narcissistic self-esteem.

PMID- 18329595
TI  - Sex differences in the relation of weight loss self-efficacy, binge eating, and
      depressive symptoms to weight loss success in a residential obesity treatment
      program.
AB  - The aim of the current study was to examine whether weight loss self-efficacy,
      binge eating, and depressive symptoms predicted weight loss during treatment, and
      whether gender moderates these associations with prospective data from 297
      participants (223 women and 74 men) enrolled in a residential obesity treatment
      program. Men reported higher initial levels of self-efficacy than women, whereas
      women reported greater pre-treatment levels of binge eating and depressive
      symptoms. Higher pre-treatment levels of weight control self-efficacy, binge
      eating, and depressive symptoms predicted greater weight loss in men, but not in
      women. Results suggest that certain psychological and behavioral factors should
      be considered when implementing weight loss interventions, and indicate a need to
      consider gender differences in predictors of weight loss treatment. Future
      research should seek to identify predictors of weight loss among women.

PMID- 18329596
TI  - Correlates of problematic eating behaviors in less acculturated Latinas.
AB  - We examined whether body weight, depression, and body dissatisfaction could
      predict problematic eating behaviors in a community sample of less acculturated
      adult Latina women. Three hundred and forty-nine Latina women ages 20-40 were
      classified as non-overeater (n=244), eating disorder not otherwise specified
      binge eating disorder features (EDNOS-BED) (n=65), or eating disorder not
      otherwise specified-bulimia nervosa features (EDNOS-BN) (n=40). Participants
      completed measures of problematic eating behaviors, depression, and body image.
      Results revealed that normal weight and overweight women were at a higher risk
      only for EDNOS-BN, while obese women were at a higher risk for either EDNOS-BN or
      EDNOS-BED. Women with high depression scores were 16 times more likely to be
      assigned to the EDNOS-BN group than women with lower depression scores. Results
      illustrate the important role of depression and body weight in predicting
      problematic eating in less acculturated Latinas.

PMID- 18329597
TI  - Effects of social context on overweight and normal-weight children's food
      selection.
AB  - Although most eating occurs in a social context, the impact of peer influence on
      child food consumption and selection of healthy and unhealthy snacks has not been
      the object of systematic experimental study. The present experiment assessed the
      effects of peer interaction on energy intake and food choices in 18 overweight
      and 21 non-overweight youth. Participants had access to high and low-calorie food
      items and were provided with several games as alternatives to eating. On one
      occasion, participants were tested alone and on another occasion they were tested
      in dyads with an unfamiliar peer. Consistent with previous results, we found that
      overweight children ate substantially more when alone than when in the presence
      of a peer and also more when alone than the lean children in the same condition.
      Non-overweight youths' food intake was unaffected by the social context. Findings
      also indicated that the best predictor of whether participants consumed healthy
      snack foods was if the other youth in the dyad also consumed healthy snack foods.
      These findings suggest that the presence of peers can influence overweight
      children's energy intake and also influence healthier food selection in both
      overweight and non-overweight children.

PMID- 18329598
TI  - The prevalence of binge eating disorder and borderline personality symptomatology
      among gastric surgery patients.
AB  - In this study, we examined the prevalence of binge eating disorder (BED) and
      borderline personality disorder (BPD) in a sample of 121 candidates seeking
      surgery for obesity. In this predominantly female sample (85.9%), according to
      the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R), the prevalence
      of BED was 6.5%. As for the prevalence of BPD, 14.0% exceeded the clinical cut
      off score on the Self-Harm Inventory (SHI), 14.0% exceeded the clinical cut-off
      score on the borderline personality scale of the Personality Diagnostic
      Questionnaire-4 (PDQ-4), and 7.4% exceeded the clinical cut-off score on the
      McLean Screening Inventory for Borderline Personality Disorder (MSI-BPD).
      Overall, 24.8% of the sample exceeded the clinical cut-off on at least one
      measure of BPD whereas only 3.3% exceeded the clinical cut-off on all three
      measures. In addition, there was a significant inverse relationship between the
      discrepancy between highest and lowest adult body mass index, and scores on the
      PDQ-4 and the MSI-BPD. The authors discuss the implications of these findings.

PMID- 18329599
TI  - Weight-based stigmatization, psychological distress, & binge eating behavior
      among obese treatment-seeking adults.
AB  - OBJECTIVE: To evaluate the associations between weight-based stigmatization,
      psychological distress, and binge eating behavior in a treatment-seeking obese
      sample. METHODS: Ninety-three obese adults completed three questionnaires: 1)
      Stigmatizing Situations Inventory, 2) Brief Symptoms Inventory, and 3) Binge
      Eating Questionnaire. Correlational analyses were used to evaluate the
      association between stigmatizing experiences, psychological distress and binge
      eating behavior. RESULTS: Stigmatizing experiences predicted both binge eating
      behavior (R(2)=.20, p<.001) and overall psychological distress (R(2)=.18,
      p<.001). A substantial amount of the variance in binge eating predicted by weight
      based stigmatization was due to the effect of psychological distress.
      Specifically, of the 20% of the variance in binge eating accounted for by
      stigmatizing experiences, between 7% and 34% (p<.01) was due to the effects of
      various indicators of psychological distress. CONCLUSIONS: These data suggest
      that weight-based stigmatization predicts binge eating behavior and that
      psychological distress associated with stigmatizing experiences may be an
      important mediating factor.

PMID- 18329600
TI  - Sensitivity to punishment and low maternal care account for the link between
      bulimic and social anxiety symptomology.
AB  - OBJECTIVE: The current study examined the joint effect of personality and
      parenting factors on the prediction of bulimia nervosa (BN) and social anxiety
      disorder (SAD) symptomology in a sample of female college students. The study
      also tested whether personality and parenting factors might account for the
      association between BN and SAD symptoms. METHOD: One-hundred twenty-eight
      participants completed self-report measures assessing maternal care (MC),
      maternal overprotection, sensitivity to punishment (SP), sensitivity to reward
      (SR), and BN and SAD symptomology. RESULTS: SP, SR, and MC each uniquely
      predicted BN symptoms, whereas only SP and MC predicted SAD symptoms. High SP
      interacted with low MC to predict BN and SAD symptoms over the main effects. In
      addition, SP, MC, and the interaction term SP x MC mediated the association
      between SAD and BN symptoms. CONCLUSION: High SP and low MC appear to account for
      the link between BN and SAD symptomology, whereas high SR appears to distinguish
      the disorders.

PMID- 18329601
TI  - Structure analysis of the Children's Eating Attitudes Test in overweight and at
      risk for overweight children and adolescents.
AB  - BACKGROUND: In school-based samples of children, the Children's Eating Attitudes
      Test (ChEAT) has a four-factor structure; however, previous studies have not
      examined its factor structure in samples restricted to overweight youth. METHODS:
      The ChEAT was administered to 220 overweight (BMI>or=95th percentile) and 45 at
      risk for overweight (BMI 85th-<95th percentile) children and adolescents. Factors
      were identified by a principal component analysis with varimax rotation. ChEAT
      factor scores of children with BMI>or=85th percentile were contrasted with those
      of 152 non-overweight (BMI 5th to <85th percentile) children and adolescents.
      RESULTS: Factor analysis generated four subscales described as 'body/weight
      concern,' 'food preoccupation,' 'dieting,' and 'eating concern.' ChEAT total
      score, body/weight concern, and dieting subscale scores were positively related
      to BMI-Z and body fat mass (p's<.05). Compared to non-overweight children,
      overweight and at-risk for overweight children had higher ChEAT total (9.9+/-7.4
      vs. 6.6+/-7.8, p<.001), body/weight concern (3.2+/-3.1 vs. 1.3+/-3.0, p<.001),
      and dieting (1.8+/-2.2 vs. .8+/-2.3, p<.001) subscale scores. CONCLUSIONS: The
      previously elucidated factor structure of the ChEAT was primarily supported in a
      sample of overweight children. The emergence of separate body/weight concern and
      dieting subscales may relate to these children's experiences with attempted
      weight reduction.

PMID- 18329602
TI  - Taking control of your personal eating and exercise environment: a weight
      maintenance program.
AB  - The current investigation examined the impact of a weight maintenance
      intervention (MI) designed to empower people to create a personal healthy food
      and physical activity environment on weight loss treatment outcomes. It was
      hypothesized that behavioral weight loss program (BWLP) participants who received
      an additional MI would evidence superior weight loss maintenance compared to
      participants who received a BWLP alone (no contact [NC]). Fifty-one obese adults
      were randomly assigned to participate in a 16-week weight loss intervention
      followed by NC or a 6-week MI. Thirty-eight participants completed the six-month
      follow-up. Body weight, percent body fat, cardiorespiratory fitness, self
      reported physical activity, and self-reported diet (i.e., calories, percent daily
      intake of fat, protein, and carbohydrates) were assessed. Participants
      significantly decreased their weight, increased physical activity/fitness, and
      improved dietary intake (ps<.05). MI participants had significantly greater
      weight loss maintenance than NC participants (ps<.05). Helping obese individuals
      to modify their personal eating and physical activity environment in order to
      reduce exposure to "obesogenic" cues may contribute to long-term weight loss
      maintenance.

PMID- 18329603
TI  - BMI as a moderator of perceived stress and emotional eating in adolescents.
AB  - Emotional eating has often been linked to overweight and/or obesity. Multiple
      group SEM analyses were conducted using cross-sectional data from 517 minority
      students in Los Angeles County. Results showed no differences in emotional eating
      between normal weight and overweight students. Perceived stress was indeed a
      significant correlate of emotional eating, independent of BMI status, as
      indicated by the lack of a modifying effect of BMI status. Findings highlight the
      fact that emotional eating is not an issue only for overweight and obese persons.
      This study shows that some children in this population at increased risk for
      obesity and related chronic disease have already incorporated emotional eating as
      a learned response to stress by the time that they enter adolescence.

PMID- 18329604
TI  - Aspects of the media and their relevance to bulimic attitudes and tendencies
      among female college students.
AB  - We examined whether media pressures would mediate the association between two
      dimensions of the media (source of information and internalization) and bulimic
      attitudes/tendencies. The study sample consisted of 106 female college students
      (M age=19.9; range=18-22). Participants completed anonymous, self-report measures
      on media influences on body image and appearance as well as disordered eating
      attitudes/behaviors. Findings showed that the association between two dimensions
      of the media (source of information and internalization) and bulimic
      attitudes/tendencies was mediated by perceived media pressures. Such findings
      highlight the significant influence of media pressures on bulimic
      attitudes/tendencies. Future research and prevention implications are discussed.

PMID- 18329605
TI  - Dietary fat intake among urban, African American adolescents.
AB  - This study examined commonly consumed high-fat food sources to estimate dietary
      fat intake among 314 urban, African American adolescents (mean age (SD)=12.57
      (.98) years; 66% female; 91% African American non-Hispanic; and 9% African
      American Hispanic). Youths' fat intake was measured using the Block Fat Screener.
      Most (77%) participants had diets very high in fat (i.e., 40% to 50% of energy).
      Mean frequencies of consumption revealed youths' preferences for the following
      high-fat food items: corn chips, potato chips, popcorn, and crackers; fried
      chicken; and doughnuts, pastries, cake, and cookies. Total fat intake differed
      based on youths' age. Urban, African American adolescents can benefit from
      intervention to lower their fat intake. Programs that target and address the food
      preferences and eating habits of this population are clearly needed.

PMID- 18329606
TI  - Staphylococcus and the healing power of pus.
AB  - Staphylococcus aureus infections induce formation of neutrophil-rich abscesses
      filled with debris from dead phagocytes. Corbin and colleagues report that this
      pus has antimicrobial powers through the activity of calprotectin. Calprotectin,
      a member of the S100 family of proinflammatory proteins, acts through chelation
      of manganese. As manganese is an essential cofactor for several enzymes in S.
      aureus, this impacts bacterial growth and the bacterium's ability to withstand
      oxidative stress.

PMID- 18329607
TI  - Bugs inside Bugs: what the fruit fly can teach us about immune and microbial
      balance in the gut.
AB  - In their coexistence with microbes, animals must fortify themselves against the
      onslaught of pathogens while maintaining a healthful consortium of resident
      commensals. In a recent paper in Science, Ryu and colleagues report that in fruit
      flies the Caudal transcription factor regulates appropriate immune responses to
      commensal bacteria, and that when these immune responses are perturbed, the gut
      microbial consortium shifts to one that is harmful to its host.

PMID- 18329608
TI  - Keeping adenovirus away from the liver.
AB  - While adenovirus holds many advantages as a vector for gene delivery, much of its
      full potential has been limited by the tendency of the most commonly used vectors
      to target the liver upon systemic delivery, resulting in unacceptable toxicity.
      Recently in Cell, Waddington et al. unmasked the virus-host interactions that
      lead to hepatic transduction. The results point a way toward avoiding this
      pathway during development of future generations of adenovirus vectors.

PMID- 18329609
TI  - A good catch: packaging the virus genome.
AB  - In tailed bacteriophages and herpesviruses, double-stranded DNA is packaged into
      a pre-existing protein shell, through a dedicated channel known as the portal. In
      a recent issue of Molecular Cell, Zheng et al. determined the structure of the
      bacteriophage P22 portal complex in pre- and postpackaging conformations,
      identifying structural changes that serve to retain the genome within the virus
      particle and prime it for injection into a new host.

PMID- 18329610
TI  - A new antituberculosis drug that selectively kills nonmultiplying Mycobacterium
      tuberculosis.
AB  - An important report by Bryk et al. in this issue of Cell Host & Microbe describes
      the properties of a rhodanine prodrug active against nonmultiplying Mycobacterium
      tuberculosis (Mtb). Considering the tolerance of nonreplicating Mtb to most
      currently available agents, such a drug could be a major addition to our
      antituberculosis arsenal and would greatly benefit control of the disease.

PMID- 18329611
TI  - Filling a GAP(DH) in asymmetric viral RNA synthesis.
AB  - Host proteins, such as RNA-binding proteins, are involved in most steps of
      replication by positive-strand RNA viruses, including Tomato bushy stunt virus
      (TBSV). In this issue of Cell Host & Microbe, Wang and Nagy report that efficient
      replication of TBSV requires GAPDH, a host protein with glycolytic, RNA-binding,
      and other functions. GAPDH binds TBSV (-)RNA and promotes the normal excess of
      (+)RNA over (-)RNA products, possibly by selectively retaining (-)RNA templates
      for copying.

PMID- 18329612
TI  - Plant NB-LRR immune receptors: from recognition to transcriptional reprogramming.
AB  - Both plants and animals contain nucleotide-binding domain and leucine-rich repeat
      (NB-LRR)-type immune receptors that function during defense against pathogens.
      Unlike animal NB-LRRs that recognize general pathogen or microbe-associated
      molecular patterns (PAMPs or MAMPs), plant NB-LRR immune receptors have evolved
      the ability to specifically recognize a wide range of effector proteins from
      different pathogens. Recent research has revealed that plant NB-LRRs are
      incredibly adaptive in their ways of pathogen recognition and defense initiation.
      This review focuses on the remarkable variety of functions, recognition
      mechanisms, subcellular localizations, and host factors associated with plant NB
      LRR immune receptors.

PMID- 18329613
TI  - Selective killing of nonreplicating mycobacteria.
AB  - Antibiotics are typically more effective against replicating rather than
      nonreplicating bacteria. However, a major need in global health is to eradicate
      persistent or nonreplicating subpopulations of bacteria such as Mycobacterium
      tuberculosis (Mtb). Hence, identifying chemical inhibitors that selectively kill
      bacteria that are not replicating is of practical importance. To address this, we
      screened for inhibitors of dihydrolipoamide acyltransferase (DlaT), an enzyme
      required by Mtb to cause tuberculosis in guinea pigs and used by the bacterium to
      resist nitric oxide-derived reactive nitrogen intermediates, a stress encountered
      in the host. Chemical screening for inhibitors of Mtb DlaT identified select
      rhodanines as compounds that almost exclusively kill nonreplicating mycobacteria
      in synergy with products of host immunity, such as nitric oxide and hypoxia, and
      are effective on bacteria within macrophages, a cellular reservoir for latent
      Mtb. Compounds that kill nonreplicating pathogens in cooperation with host
      immunity could complement the conventional chemotherapy of infectious disease.

PMID- 18329614
TI  - Caspase-12 modulates NOD signaling and regulates antimicrobial peptide production
      and mucosal immunity.
AB  - Bacterial sensing by intracellular Nod proteins and other Nod-like receptors
      (NLRs) activates signaling pathways that mediate inflammation and pathogen
      clearance. Nod1 and Nod2 associate with the kinase Rip2 to stimulate NF-kappaB
      signaling. Other cytosolic NLRs assemble caspase-1-activating multiprotein
      complexes termed inflammasomes. Caspase-12 modulates the caspase-1 inflammasome,
      but unlike other NLRs, Nod1 and Nod2 have not been linked to caspases, and
      mechanisms regulating the Nod-Rip2 complex are less clear. We report that caspase
      12 dampens mucosal immunity to bacterial infection independent of its effects on
      caspase-1. Caspase-12 deficiency enhances production of antimicrobial peptides,
      cytokines, and chemokines to entric pathogens, an effect dependent on bacterial
      type III secretion and the Nod pathway. Mechanistically, caspase-12 binds to
      Rip2, displacing Traf6 from the signaling complex, inhibiting its ubiquitin
      ligase activity, and blunting NF-kappaB activation. Nod activation and resulting
      antimicrobial peptide production constitute an early innate defense mechanism,
      and caspase-12 inhibits this mucosal antimicrobial response.

PMID- 18329615
TI  - Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase
      and induces T cell hyperactivation.
AB  - Symptoms of T cell hyperactivation shape the course and outcome of HIV-1
      infection, but the mechanism(s) underlying this chronic immune activation are not
      well understood. We find that the viral transactivator Tat promotes
      hyperactivation of T cells by blocking the nicotinamide adenine dinucleotide
      (NAD(+))-dependent deacetylase SIRT1. Tat directly interacts with the deacetylase
      domain of SIRT1 and blocks the ability of SIRT1 to deacetylate lysine 310 in the
      p65 subunit of NF-kappaB. Because acetylated p65 is more active as a
      transcription factor, Tat hyperactivates the expression of NF-kappaB-responsive
      genes, a function lost in SIRT1-/- cells. These results support a model where the
      normal function of SIRT1 as a negative regulator of T cell activation is
      suppressed by Tat during HIV infection. These events likely contribute to the
      state of immune cell hyperactivation found in HIV-infected individuals.

PMID- 18329616
TI  - Ebola virus matrix protein VP40 uses the COPII transport system for its
      intracellular transport.
AB  - The Ebola virus matrix protein VP40 plays an important role in virion formation
      and viral egress from cells. However, the host cell proteins and mechanisms
      responsible for intracellular transport of VP40 prior to its contribution to
      virion formation remain to be elucidated. Therefore we used coimmunoprecipitation
      and mass spectrometric analyses to identify host proteins interacting with VP40.
      We found that Sec24C, a component of the host COPII vesicular transport system,
      interacts specifically with VP40 via VP40 amino acids 303 to 307.
      Coimmunoprecipitation and dominant-negative mutant studies indicated that the
      COPII transport system plays a critical role in VP40 intracellular transport to
      the plasma membrane. Marburg virus VP40 was also shown to use the COPII transport
      system for intracellular transport. These findings identify a conserved
      intersection between a host pathway and filovirus replication, an intersection
      that can be targeted in the development of new antiviral drugs.

PMID- 18329617
TI  - Tomato bushy stunt virus co-opts the RNA-binding function of a host metabolic
      enzyme for viral genomic RNA synthesis.
AB  - Tomato bushy stunt virus (TBSV), a plus-stranded [(+)] RNA plant virus,
      incorporates the host metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase
      (GAPDH) into the viral replicase complex. Here, we show that, during TBSV
      replication in yeast, the yeast GAPDH Tdh2p moves from the cytosol to the
      peroxisomal membrane surface, the site of viral RNA synthesis. In yeast cells
      lacking Tdh2p, decreasing the levels of its functionally redundant homolog Tdh3p
      inhibited TBSV replication and resulted in equivalent levels of (+) and minus
      stranded [(-)] viral RNA, in contrast to the hallmark excess of (+)RNA. Tdh2p
      specifically bound an AU pentamer sequence in the (-)RNA, suggesting that GAPDH
      promotes asymmetric RNA synthesis by selectively retaining the (-)RNA template in
      the replicase complex. Downregulation of GAPDH in a natural plant host decreased
      TBSV genomic RNA accumulation. Thus, TBSV co-opts the RNA-binding function of a
      metabolic protein, helping convert the host cell into a viral factory.

PMID- 18329618
TI  - A malaria parasite formin regulates actin polymerization and localizes to the
      parasite-erythrocyte moving junction during invasion.
AB  - Malaria parasites invade host cells using actin-based motility, a process
      requiring parasite actin filament nucleation and polymerization. Malaria and
      other apicomplexan parasites lack Arp2/3 complex, an actin nucleator widely
      conserved across eukaryotes, but do express formins, another type of actin
      nucleator. Here, we demonstrate that one of two malaria parasite formins,
      Plasmodium falciparum formin 1 (PfFormin 1), and its ortholog in the related
      parasite Toxoplasma gondii, follows the moving tight junction between the
      invading parasite and the host cell, which is the predicted site of the
      actomyosin motor that powers motility. Furthermore, in vitro, the PfFormin1 actin
      binding formin homology 2 domain is a potent nucleator, stimulating actin
      polymerization and, like other formins, localizing to the barbed end during
      filament elongation. These findings support a conserved molecular mechanism
      underlying apicomplexan parasite motility and, given the essential role that
      actin plays in cell invasion, highlight formins as important determinants of
      malaria parasite pathogenicity.

PMID- 18329619
TI  - Suramin and minocycline treatment of experimental African trypanososmiasis at an
      early stage of parasite brain invasion.
AB  - The effect of treatment on relapses of Trypanosoma brucei (T. b.) brucei
      infections in mice in relation to passage of the parasites across the blood-brain
      barrier (BBB) as visualized by immunohistochemistry was studied. Three daily
      intraperitoneal injections of 20mg/kg suramin starting at 15 days post-infection
      (p.i.), when trypanosomes had begun to traverse the BBB, were curative, but not
      when starting at 21 days p.i. when parasite brain invasion was more pronounced.
      Relapses occurred in all mice after one or two daily injections of suramin
      starting at 15 days p.i., but they were delayed when treatment was supplemented
      with minocycline, which impedes penetration of T. b. brucei into the brain. This
      study supports the notion that suramin may be effective even when minor parasite
      neuroinvasion has appeared in African trypanosomiasis and it shows that
      minocyline can affect relapses of the disease.

PMID- 18329620
TI  - Influence of Brugia malayi life stages and BmAFII fraction on experimental
      Leishmania donovani infection in hamsters.
AB  - The influence of live Brugia malayi parasites and a Sephadex G-200 fraction of
      the adult parasite extract (BmAFII) on the progression of Leishmania donovani
      infection was studied. Inbred hamsters were first infected with B. malayi
      infective 3rd stage larvae (L3), adult worms or microfilariae (mf), and then with
      L. donovani amastigotes (Ld), or vice versa or received both the infections
      simultaneously; a group of animals were first immunized with BmAFII and then
      infected with Ld. L. donovani parasite burden was determined between 17 and 19
      days post amastigote challenge (p.a.c.) and, in case of immunized animals,
      between 32 and 35 days p.a.c also. Nitric oxide (NO) release from peritoneal
      macrophages and cellular proliferative responses of lymphnode cells were assessed
      in BmAFII-immunized animals given leishmania infection or no infection.
      Leishmanial parasite burden was significantly reduced in animals exposed to
      filarial L3 before amastigote inoculation and in animals given filarial adult
      worms after or together with amastigotes. Prior immunization of leishmania
      infected animals with BmAFII also reduced the leishmanial parasite burden (17-19
      days p.a.c.: >90%; 32-35 days p.a.c.: 60%). These animals showed upregulation of
      NO release and cellular proliferative responses to promastigote antigen or BmAFII
      stimulation in vitro. The findings show, for the first time, that B. malayi
      L3/adult worms or immunization with BmAFII inhibits progression of L. donovani
      infection in hamsters and this is associated with upregulation of NO and
      lymphocyte proliferative responses indicating that Th1 response might be
      responsible for this.

PMID- 18329621
TI  - Genetic testing and breach of patient confidentiality: law, ethics, and
      pragmatics.
AB  - Medical uses of genetic information have multiplied over the last several years.
      When an individual is a carrier of a clinically important allele, their kindred
      are at increased risk of carrying the same allele and of sharing the consequent
      risk of disease. If there were an intervention that could modify the risk of
      progression to disease, then there would be a clear advantage to kindred to be so
      informed. However, some probands may resist divulging that information to kindred
      for any of a variety of reasons, including the potential for discrimination. In
      this article we will review the manner in which the courts and professional
      organizations have viewed the conflict between 1 individual's right to privacy
      and another's right to information that could potentially be life saving or life
      prolonging. We will then consider the ethics of this issue and suggest an
      approach that physicians should take when confronting it.

PMID- 18329622
TI  - The variation in optical coherence tomography-measured macular thickness in
      diabetic eyes without clinical macular edema.
AB  - PURPOSE: To determine the variation in optical coherence tomography (OCT)
      measured macular thickness in diabetic eyes without clinical edema and to
      investigate factors that might influence variation in macular thickness. DESIGN:
      Retrospective, observational case series from a clinical practice. METHODS:
      Review of clinical charts and longitudinal OCT measurements of a consecutive
      series of 56 eyes of 56 patients with diabetes but no clinical macular edema.
      Measured variables include OCT central subfield mean thickness (CSMT), total
      macular volume (TMV), and logarithm of the minimum angle of resolution (logMAR)
      visual acuity. RESULTS: Over a median follow-up of 17 months, interquartile range
      (IQR) (9, 23), the median variation in CSMT was 18 microns, IQR (11, 31), and the
      median variation in TMV was 0.09 mm(3), IQR (0.06, 0.16). Variation in CSMT did
      not change significantly with increasing CSMT. Absolute, but not relative,
      variation in TMV increased with increasing baseline values (P = .0127 and P =
      .1538 for absolute variation and relative variation in TMV, respectively). The
      variation in CSMT and TMV did not vary with follow-up time and did not vary with
      age, gender, race, hypertension status, glycosylated hemoglobin, or retinopathy
      level. CONCLUSIONS: Variation in CSMT and TMV in diabetic eyes without DME over
      intervals up to 17 months is no greater than OCT measurement variability in eyes
      without and with DME. A change in the OCT-measured macular thickness greater than
      10% of the baseline thickness is likely to represent a true change in the macular
      thickness and not OCT measurement variability, diurnal variation, or variability
      occurring over longer time scales.

PMID- 18329623
TI  - Fundus autofluorescence in multifocal choroiditis and panuveitis.
AB  - PURPOSE: To investigate the autofluorescence findings associated with multifocal
      choroiditis and panuveits (MCP), a condition that has marked potential to affect
      the retinal pigment epithelium (RPE). DESIGN: Observational case series. METHODS:
      This is a retrospective review of consecutive patients with MCP examined in a
      retinal referral practice. Each patient was given a comprehensive examination
      including fundus photographs, angiographic studies, and autofluorescence
      photography with an excitation filter with the bandpass wavelengths of 535 to 585
      nm and a barrier filter with a bandpass of 615 to 715 nm. Integrative analysis
      was performed of the ocular imaging to ascertain abnormalities caused by the
      disease. RESULTS: Thirty-six eyes of 18 consecutive patients were evaluated. The
      mean duration of symptoms was 86.2 months and the mean visual acuity was 20/50.
      Of the 36 eyes, 23 had choroidal neovascularization (CNV). Chorioretinal
      hypoautofluorescent spots >or= 125 microns usually, but not always, had the
      clinically evident correlate of a punched-out scar visible by color fundus
      photography. Chorioretinal hypoautofluorescent spots less than 125 microns, which
      could number in the hundreds, typically were not visible by color fundus
      photography. All chorioretinal scars visible by color fundus photography were
      visible by autofluorescence photography. During follow-up many patients developed
      new clinically evident chorioretinal scars, which were presaged in earlier
      autofluorescence photographs. CNV had a hyperautofluorescent boundary, making it
      readily visible. CONCLUSIONS: Patients with MCP have much more widespread
      involvement of the RPE than would be suspected by other means of imaging.
      Autofluorescence photography supplies information about inflammatory damage and
      secondary CNV in a noninvasive manner.

PMID- 18329624
TI  - Endophthalmitis associated with intravitreal anti-vascular endothelial growth
      factor therapy injections in an office setting.
AB  - PURPOSE: To determine the incidence of endophthalmitis following intravitreal
      injection of anti-vascular endothelial growth factor (VEGF) agents. DESIGN: A
      retrospective interventional case series. METHODS: A total of 10,254 intravitreal
      anti-VEGF injections (406 pegaptanib, 3,501 bevacizumab, and 6,347 ranibizumab)
      were performed from January 5, 2005 to October 18, 2007. The number of the
      injections was determined from the injection log books and billing records. The
      injections were performed as an office based procedure with use of povidone
      iodine as a part of preinjection preparation. Preinjection antibiotics, eye
      drape, or surgical attire were not used. The main outcome measures were the
      incidence of suspected and proven endophthalmitis. RESULTS: There were three
      cases of suspected endophthalmitis, one case following bevacizumab injection and
      two cases following ranibizumab injection. There was no case of culture-proven
      endophthalmitis. All three patients regained their preinjection visual acuity.
      The incidence of suspected endophthalmitis was 0.029% (95% confidence interval,
      0.006% to 0.085%). There was no difference in the incidence of endophthalmitis
      between ranibizumab and bevacizumab injections (P = .6). CONCLUSIONS: Although
      there is no consensus regarding the intravitreal injection procedure technique,
      the incidence of suspected endophthalmitis was very low in a large series of
      injected patients in a community setting and the incidence compares favorably
      with that reported in clinical trials where much more extensive preinjection
      preparation was mandated. We found no difference in the endophthalmitis risk of
      patients receiving bevacizumab as compared with ranibizumab.

PMID- 18329625
TI  - Influence of persistent submacular fluid on visual outcome after successful
      scleral buckle surgery for macula-off retinal detachment.
AB  - PURPOSE: To determine the influences of the extent and duration of persistent
      submacular fluid on final visual outcome after successful scleral buckle surgery
      for acute macula-off rhegmatogenous retinal detachment (RD). DESIGN: Prospective
      observational case series. METHODS: Forty-four consecutive patients (44 eyes) who
      underwent successful scleral buckle surgery for macula-off rhegmatogenous RD were
      enrolled patients underwent thorough ophthalmologic tests including best
      corrected visual acuity (BCVA) assessments and optical coherence tomography (OCT)
      at one, three, six, nine, and 12 months postoperatively, until at least six
      months after the disappearance of subretinal fluid (SRF). Patients with
      persistent submacular fluid one month after surgery were assigned to group A and
      those without submacular fluid, to group B. In group A, patients whose submacular
      fluid disappeared before six months were assigned to group A1; the others, to
      group A2. The natural course of persistent SRF and associations between the
      extent and duration of SRF and postoperative BCVA were investigated. RESULTS:
      Twenty-three eyes (52.3%) were in group A and 21 eyes (47.7%) in group B. Twelve
      eyes (52.2%) were in group A1 and 11 eyes (47.8%) in group A2. SRF disappeared
      within 12 months after surgery without reoperation in all patients. No
      significant differences in final visual acuity (VA) were found among groups A, B,
      A1, and A2. Final VA was not found to be associated with SRF extent or duration.
      CONCLUSIONS: The presence and extent of submacular fluid after successful scleral
      buckle surgery for acute macula-off rhegmatogenous RD did not influence final VA
      or anatomic attachment.

PMID- 18329626
TI  - Sutureless amniotic membrane transplantation for partial limbal stem cell
      deficiency.
AB  - PURPOSE: To evaluate the results of sutureless amniotic membrane (AM)
      transplantation using fibrin glue for reconstructing corneal surfaces with
      partial limbal stem cell deficiency (LSCD). DESIGN: Retrospective noncomparative
      interventional case series. METHODS: Eleven eyes of nine patients that had LSCD
      with 120 degrees to almost 360 degrees of limbal involvement underwent
      superficial keratectomy to remove the conjunctivalized pannus followed by AM
      transplantation using fibrin glue. Additional sutureless AM patch (ProKera; Bio
      Tissue, Inc, Miami, Florida, USA) was used in seven patients, and mitomycin C was
      applied on the cornea in four eyes and during fornix reconstruction in seven
      eyes. The surgery was repeated in three eyes for residual pannus. RESULTS: During
      a mean follow-up of 14.2 +/- 7.7 months (range, six to 26 months), all eyes
      maintained a smooth and stable corneal epithelial surface without recurrent
      erosion or persistent epithelial defect, and showed less stromal cloudiness and
      vascularization. Best-corrected visual acuity improved in nine eyes (81.8%).
      Corneal epithelialization proceeded by epithelial growth over AM (n = 4),
      accompanied by dissolution of AM (n = 4) or a combination of both (n = 3). No
      complication was noted regarding initial or repeated uses of fibrin glue.
      CONCLUSION: AM transplantation using fibrin glue appears to be a safe and
      effective method of restoring a stable corneal epithelium for cases with partial
      LSCD. This approach avoids the need of transplanting limbal epithelial stem
      cells.

PMID- 18329627
TI  - Intraocular pressure measurements following Descemet stripping endothelial
      keratoplasty.
AB  - PURPOSE: The effect of increased corneal thickness after Descemet stripping
      endothelial keratoplasty (DSEK) on intraocular pressure (IOP) measurement has not
      been previously studied. It is uncertain if this increase in corneal thickness
      would artificially elevate IOP reading by Goldmann tonometry [GAT] (Haag-Streit,
      Konig, Switzerland). Therefore the effect of DSEK-related thick cornea on IOP
      measurement was investigated using three different techniques. DESIGN:
      Prospective cross-sectional study. METHODS: Participants were recruited from a
      single tertiary referral center. Fifty eyes of 38 patients with successful DSEK
      at least three months prior to testing were evaluated. At the time of the study,
      none of the participants had clinically detectable corneal edema. IOP was
      measured with GAT, pneumatonometry, and dynamic contour tonometry (DCT) in an
      unmasked randomized sequence. Central corneal thickness (CCT) was measured by
      ultrasonic pachymetry. RESULTS: Mean CCT was 701 +/- 68 microm. The mean IOP +/-
      standard deviation (SD) was 15.9 +/- 4.9 mm Hg for GAT, 20.3 +/- 4.5 mm Hg for
      pneumatonometry, and 19.8 +/- 4.4 mm Hg for DCT. Pneumatonometry and DCT IOP
      measurements were significant higher than GAT (P < .01). In contrast, the
      difference between pneumatonometry and DCT readings was not statistically
      significant (P = .28). The correlations between IOP and corneal thickness were
      not significant in this cohort (P > .05). CONCLUSIONS: Falsely elevated GAT, as
      expected in thick corneas, was not demonstrated after DSEK. High IOP reading by
      GAT therefore should raise suspicion of elevated IOP in DSEK eyes.

PMID- 18329628
TI  - A visual ergonomic evaluation of different screen types and screen technologies
      with respect to discrimination performance.
AB  - An increasing demand to work with electronic displays and to use mobile computers
      emphasises the need to compare visual performance while working with different
      screen types. In the present study, a cathode ray tube (CRT) was compared to an
      external liquid crystal display (LCD) and a Notebook-LCD. The influence of screen
      type and viewing angle on discrimination performance was studied. Physical
      measurements revealed that luminance and contrast values change with varying
      viewing angles (anisotropy). This is most pronounced in Notebook-LCDs, followed
      by external LCDs and CRTs. Performance data showed that LCD's anisotropy has
      negative impacts on completing time critical visual tasks. The best results were
      achieved when a CRT was used. The largest deterioration of performance resulted
      when participants worked with a Notebook-LCD. When it is necessary to react
      quickly and accurately, LCD screens have disadvantages. The anisotropy of LCD
      TFTs is therefore considered to be as a limiting factor deteriorating visual
      performance.

PMID- 18329629
TI  - Using enhanced text to facilitate recognition of drug names: evidence from two
      experimental studies.
AB  - Two studies examined the effects of enhanced text on immediate recognition of
      drug names. Study 1 sampled 102 college students using a between-subjects design,
      while Study 2 sampled 11 practicing pharmacists and technicians using a within
      subjects Latin square design. Both studies utilized a computer-based sequential
      recognition task where a prime word was shown with various text enhancements,
      followed by a mask and then a target word. Participants decided whether the
      target word was the same as the prime word. Stimuli were organized so that 120
      trials were matches and 120 trials were mismatches, randomly sequenced for each
      participant. Results showed an effect of orthographic similarity, where high
      similarity name mismatches were missed more often. This effect was independent of
      the type of text enhancement used and response bias. Case-based enhancements also
      increased errors of commission (false alarms) significantly. Discussion includes
      the practical relevance of the data and future directions for research.

PMID- 18329630
TI  - Quercetin pretreatment increases the bioavailability of pioglitazone in rats:
      involvement of CYP3A inhibition.
AB  - Herbal antidiabetic preparations are often used as an add-on therapy in diabetes
      and such herbal preparations often contains quercetin that can inhibit cytochrome
      P450 (CYP) 3A4. This enzyme is responsible for metabolizing pioglitazone, a
      commonly used antidiabetic agent. Hence, it was speculated that quercetin may
      influence the bioavailability of pioglitazone, which could be particularly
      crucial, as any increment in its plasma levels may raise safety concerns. Thus,
      we first established the inhibitory influence of quercetin (2, 10 and 20 mg/kg,
      p.o.) on CYP3A activity by an in vivo method of estimating levels of midazolam in
      female rats pretreated with dexamethasone. It was further confirmed in vitro
      using erythromycin-N-demethylase (EMD) assay. These studies indicated potent
      inhibition of CYP3A activity by quercetin (10 and 20 mg/kg, in vivo; 1 and 10
      microM, in vitro). In another experiment, pioglitazone was administered orally
      (10 mg/kg) and intravenously (5mg/kg) to quercetin (10 mg/kg) pretreated female
      rats and its plasma levels were determined at various time points (0.5, 1, 2, 4,
      8 and 24 h after oral administration; 0.083, 0.5, 1, 2, 8, 12 and 18 h after i.v.
      administration) by HPLC. Quercetin pretreatment increased AUC(0-infinity) of
      pioglitazone after oral administration by 75% and AUC(0-infinity) after
      intravenous administration by 25% suggesting decreased metabolism, which could be
      due to inhibition of CYP3A by quercetin. In conclusion, add-on preparations
      containing quercetin may increase the bioavailability of pioglitazone, and hence
      should be cautiously used.

PMID- 18329631
TI  - Effects of estrogen on intracellular signaling pathways linked to activation of
      muscarinic acetylcholine receptors and on acetylcholinesterase activity in rat
      hippocampus.
AB  - The aim of the present study was to investigate the effects of estrogen lack and
      estrogen replacement on the production of total [3H]inositol phosphate ([3H]IP)
      induced by the activation of muscarinic acetylcholine receptors (mAChRs) and on
      the mechanisms for inactivation of acetylcholine. Hippocampi were obtained from
      rats in proestrus (PE), ovariectomized for 15 days (C15), ovariectomized for 15
      days and then treated with 17beta-estradiol for 7 days (E7) and ovariectomized
      and immediately treated with 17beta-estradiol for 21 days (E21). Ovariectomy did
      not change the basal level of total [3H]IP in the hippocampus. 17beta-Estradiol
      replacement (E7 and E21) reduced the basal level of total [3H]IP. In all
      experimental groups, carbachol (CCh) caused a concentration-dependent rise in
      total [3H]IP. The maximum effect was reached with 10(-4) M CCh. The response to
      10(-4) M CCh in the hippocampi from C15 and E7 rats was twofold higher than in
      hippocampi from PE and E21 animals and was blocked by pirenzepine, but not by
      methoctramine. Ovariectomy or 17beta-estradiol treatment for 7 days did not
      change neither the total acetylcholinesterase (AChE) activity nor the relative
      amount of mono- and dimeric G1/G2 and tetrameric G4 globular forms. Conversely,
      hormonal treatment for 21 days induced an increase in AChE activity of G1/G2 and
      G4 forms, indicating that 17beta-estradiol stimulates both synthesis and assembly
      of AChE molecular forms. The present results suggest that the duration and/or a
      critical period with regard to the initiation of estrogen therapy are important
      to regulate the function of mAChRs and AChE activity in female rat hippocampus.

PMID- 18329632
TI  - Modulatory effects of 5-fluorouracil on the rhythmic expression of circadian
      clock genes: a possible mechanism of chemotherapy-induced circadian rhythm
      disturbances.
AB  - The circadian clock system is necessary to adapt endogenous physiological
      functions to daily variations in environmental conditions. Abnormality in
      circadian rhythms, such as the sleep-wake cycle and the timing of hormonal
      secretions, is implicated in various physiological and psychiatrical disorders.
      Recent molecular studies have revealed that oscillation in the transcription of
      specific clock genes plays a central role in the generation of 24h cycles of
      physiology and behavior. It has been noticed that patients receiving
      chemotherapeutic agents experience disturbances in their behavioral and physical
      performances, including circadian rhythms. To explore the underlying mechanism of
      chemotherapeutic agent-induced disturbance of these rhythms, we investigated the
      influence of 5-fluorouracil (5-FU), one of the most widely used chemotherapeutic
      agents for the treatment of cancers, on the expression of clock genes. Treatment
      of cultured NIH3T3 cells with 5-FU for 48 h resulted in a significant reduction
      of mRNA levels of Period1 (Per1) and Period2 (Per2) without affecting cell
      viability; however, treatment with the same amount of uracil, a structural analog
      of 5-FU, had little effect on the expression of clock genes. Consistent with its
      inhibitory actions, continuous administration of 5-FU (2 mg/kg/h) to mice
      attenuated the oscillation in the expressions of Per1 and Per2 in the liver and
      suprachiasmatic nuclei, the center of the mammalian circadian clock. These
      results reveal a possible pharmacological action by the chemotherapeutic agent 5
      FU on the circadian clock mechanism, which is the underlying cause of its adverse
      effects on 24-h rhythms of physiology and behavior.

PMID- 18329633
TI  - Covert orienting of attention and overt eye movements activate identical brain
      regions.
AB  - This study investigated the anatomical relationship between covert and overt
      shifts of attention. Previous studies have found that the areas of the brain
      activated by covert and overt shifts of attention are very similar. However,
      despite a general agreement between studies there are a few issues that merit
      closer inspection. Primarily, the tasks aiming to produce covert or overt shifts
      of attention were not always comparable. Secondly, the previous studies disagreed
      on whether greater neural activity is elicited by covert shifts or overt shifts
      of attention. Thirdly, the previous studies differed on whether the shifts of
      attention were exogenously or endogenously driven. Finally, the statistical
      analyses used by all previous studies failed to account for between subject
      variability. The present study was designed to address all these issues. Twelve
      healthy subjects performed either covert or overt shifts of attention while the
      functional magnetic resonance imaging (fMRI) signal was continuously measured. In
      line with the previous studies, the present study showed a virtually complete
      overlap between areas of the brain recruited during covert shifts of attention
      and areas of the brain recruited during overt shifts of attention. Furthermore,
      using endogenously driven shifts of attention this study found that overt shifts
      of attention resulted in higher levels of activation in the brain than covert
      shifts of attention. The results of this study provide support for the premotor
      theory of attention that posits that the attentional and motor systems are the
      result of neural activation in the same areas of the brain.

PMID- 18329634
TI  - Antioxidants prevent ethanol-associated apoptosis in fetal rhombencephalic
      neurons.
AB  - It is well known that ethanol damages the developing nervous system by augmenting
      apoptosis. Previously, this laboratory reported that ethanol augments apoptosis
      in fetal rhombencephalic neurons, and that the increased apoptosis is associated
      with reduced activity of the phosphatidylinositol 3-kinase pathway and downstream
      expression of pro-survival genes. Other laboratories have shown that another
      mechanism by which ethanol induces apoptosis in developing neurons is through the
      generation of reactive oxygen species (ROS) and the associated oxidative stress.
      The present study used an in vitro model to investigate the potential
      neuroprotective effects of several antioxidants against ethanol-associated
      apoptosis in fetal rhombencephalic neurons. The investigated antioxidants
      included three phenolics: (-)-epigallocatechin-3-gallate (EGCG), a flavanoid
      polyphenol found in green tea; curcumin, found in tumeric; and resveratrol
      (3,5,4'-trihydroxystilbene), a component of red wine. Additional antioxidants,
      including melatonin, a naturally occurring indole, and alpha-lipoic acid, a
      naturally occurring dithiol, were also investigated. These studies demonstrated
      that a 24-hour treatment of fetal rhombencephalic neurons with 75 mM ethanol
      caused a 3-fold increase in the percentage of apoptotic neurons. However, co
      treatment of these cultures with any of the five different antioxidants prevented
      ethanol-associated apoptosis. Antioxidant treatment did not alter the extent of
      apoptosis in control neurons, i.e., those cultured in the absence of ethanol.
      These studies showed that several classes of antioxidants can exert
      neuroprotection against ethanol-associated apoptosis in fetal rhombencephalic
      neurons.

PMID- 18329635
TI  - Peripheral injection of ghrelin induces Fos expression in the dorsomedial
      hypothalamic nucleus in rats.
AB  - Peripheral ghrelin has been shown to act as a gut-brain peptide exerting a potent
      orexigenic effect on food intake. The dorsomedial nucleus of the hypothalamus
      (DMH) is innervated by projections from other brain areas being part of the
      network of nuclei controlling energy homeostasis, among others NPY/AgRP-positive
      fibers arising from the arcuate nucleus (ARC). The aim of the study was to
      determine if peripherally administered ghrelin affects neuronal activity in the
      DMH, as assessed by Fos expression. The number of Fos positive neurons was
      determined in the DMH, paraventricular nucleus of the hypothalamus (PVN), ARC,
      ventromedial hypothalamic nucleus (VMH), nucleus of the solitary tract (NTS) and
      in the area postrema (AP) in non-fasted Sprague-Dawley rats in response to
      intraperitoneally (ip) injected ghrelin (3 nmol/rat) or vehicle (0.15 M NaCl).
      Peripheral ghrelin induced a significant increase in the number of Fos-ir
      positive neurons/section compared with vehicle in the ARC (mean+/-SEM: 49+/-2 vs.
      23+/-2 neurons/section, p=0.001), PVN (69+/-5 vs. 34+/-3, p=0.001), and DMH
      (142+/-5 vs. 83+/-5, p<0.001). Fos-ir positive neurons were mainly localized
      within the ventral part of the DMH. No change in Fos expression was observed in
      the VMH (53+/-8 vs. 48+/-6, p=0.581), NTS (42+/-2 vs. 40+/-3, p=0.603), and in
      the AP (7+/-1 vs. 5+/-1, p=0.096). Additional double-labelling with anti-Fos and
      anti-AgRP revealed that Fos positive neurons in the DMH were encircled by a
      network of AgRP-ir positive fibers. These data indicate that peripheral ghrelin
      activates DMH neurons and that NPY-/AgRP-positive fibers may be involved in the
      response.

PMID- 18329636
TI  - A tetrahydro beta-carboline trisaccharide from Palicourea coriacea (Cham.) K.
      Schum.
AB  - A new tetrahydro beta-carboline alkaloid that has an oligosaccharide unit was
      isolated from the root extracts of the Palicourea coriacea. The structure was
      elucidated using spectral methods, including 2D NMR: COSY, HMQC, HMBC and NOESY.

PMID- 18329637
TI  - A preliminary study on the seasonal body temperature rhythms of the captive
      mountain hare (Lepus timidus).
AB  - The mountain hare (Lepus timidus) is a year-round active herbivore adapted to
      survive the boreal winter. Captive mountain hares (N=4) were implanted with
      intraabdominal thermosensitive loggers to record their core body temperature
      (T(b)) for a year and during food deprivation (8-48h) in summer and winter. The
      average T(b) was 38.7+/-0.01 degrees C in summer and 38.3+/-0.01 degrees C in
      winter. The yearly T(b) correlated positively with the ambient temperature. The
      24-h T(b) was the highest from late scotophase to early photophase in summer and
      winter and the lowest during middle-late photophase in summer or during early
      middle scotophase in winter. The range of the 24-h oscillations in T(b) increased
      in three animals in winter. Food deprivation did not induce hypothermia in summer
      or winter. These preliminary data suggest that the mountain hare can spare a
      modest amount of energy with the wintertime reduction in T(b).

PMID- 18329638
TI  - Requirement for Wnt and FGF signaling in Xenopus tadpole tail regeneration.
AB  - We have investigated the requirement for the FGF and Wnt/beta-catenin pathways
      for Xenopus tadpole tail regeneration. Pathways were modified either by treatment
      with small molecules or by induction of transgene expression with heat shocks.
      Regeneration is inhibited by treatment with the FGF inhibitor SU5402, or by
      activation of a dominant negative FGF receptor, or by activation of expression of
      the Wnt inhibitor Dkk1. Agents promoting Wnt activity: the small molecule BIO, or
      a constitutively active form of beta-catenin, led to an increased growth rate.
      Combination of a Wnt activator with FGF inhibitor suppressed regeneration, while
      combination of a Wnt inhibitor with a FGF activator allowed regeneration. This
      suggests that the Wnt activity lies upstream of the FGF activity. Expression of
      both Wnt and FGF components was inhibited by activation of noggin, suggesting
      that BMP signalling lies upstream of both Wnt and FGF. The results show that the
      molecular mechanism of Xenopus tadpole tail regeneration is surprisingly similar
      to that of the Xenopus limb bud and the zebrafish caudal fin, despite the
      difference of anatomy.

PMID- 18329639
TI  - Anti-tumor effects of paeonol in a HepA-hepatoma bearing mouse model via
      induction of tumor cell apoptosis and stimulation of IL-2 and TNF-alpha
      production.
AB  - Paeonol, a phenolic component from the root bark of Paeonia moutan, is
      traditionally used as a Chinese herbal medicine to activate the blood flow and
      remove blood stasis. Evidence shows that paeonol have anti-tumor, anti
      inflammatory, and analgesic effects; however, the underlying mechanisms remain
      unknown. In this study, we investigated the molecular mechanisms by which paeonol
      exerts the anti-tumor effects by using a murine model of hepatoma established by
      in vivo injection of mouse HepA-hepatoma cells. Treatment of mice with 100, 200,
      or 400 mg/kg/day of paeonol significantly inhibited the growth of the HepA tumor
      in mice, induced HepA cell apoptosis as demonstrated by light microscopy and
      electron microscopy analyses, decreased the expression of Bcl-2 and increased the
      expression of Bax in HepA tumor tissues in a dose-related manner. Administration
      of paeonol in vivo also elevated serum levels of IL-2 and TNF-alpha in tumor
      bearing mice. Moreover, splenocytes and macrophages isolated from paeonol-treated
      HepA tumor-bearing mice produced higher levels of IL-2 and TNF-alpha in response
      to concanavalin A and lipopolysaccharide stimulation, respectively, compared to
      these isolated from non-treated HepA tumor-bearing mice. In vitro treatment with
      paeonol was able to directly stimulate IL-2 and TNF-alpha production in
      splenocytes and macrophages from tumor-bearing mice, respectively. In conclusion,
      paeonol has the anti-tumor effect against hepatoma cells, which are likely
      mediated via induction of tumor cell apoptosis and stimulation of IL-2 and TNF
      alpha production. Paeonol could be a promising drug to treat hepatocellular
      carcinoma.

PMID- 18329640
TI  - Suitability of tamoxifen-induced mutagenesis for behavioral phenotyping.
AB  - Tamoxifen-induced mutagenesis via the so-called CreER(T2) fusion enzyme is a key
      technology for the inducible gene knockout in the adult murine brain. However, it
      requires a subchronic transient treatment with high doses of the non-selective
      estrogen receptor antagonist tamoxifen. It has been shown earlier that acute
      tamoxifen treatment causes behavioral alterations, while the long-term behavioral
      effects of tamoxifen in mice are so far unknown. Therefore C57BL/6 male mice, a
      common strain used for targeted mutagenesis and behavioral analyses, were
      subjected to a tamoxifen treatment protocol as used for inducible mutagenesis in
      vivo, and analyzed for effects on general behavior (locomotion, exploration),
      emotional behavior (anxiety, depression) and on learning and memory after a drug
      free interval period of 4 weeks. The results demonstrate that a test for
      depression-like behavior, i.e. the Forced Swim Test, is affected even more than 4
      weeks after tamoxifen treatment. In contrast, in all other tests, tamoxifen
      treated mice showed unaltered behaviors, indicating that the currently
      established 5-day protocol of tamoxifen treatment (40 mg/kg bid) for inducible
      mutagenesis has no or little effects on the behavior of C57BL/6 male mice after a
      latency period of 4 weeks. These results are important for all studies using
      tamoxifen-induced mutagenesis since this protocol obviously does not evoke
      alterations in general behaviors such as locomotion, exploration or anxiety-like
      behaviors, which might confound more complex behavioral analyses, nor does it
      affect standard tests for learning and memory, such as Morris Water Maze,
      contextual and cued Fear Conditioning and T-Maze learning.

PMID- 18329641
TI  - TaqMan real-time PCR assay for specific detection of Opisthorchis viverrini DNA
      in Thai patients with hepatocellular carcinoma and cholangiocarcinoma.
AB  - The aim of this study was to develop TaqMan real-time PCR assay that detected
      Opisthorchis viverrini DNA from 18 normal and 18 tumor tissue specimens from Thai
      patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), who
      underwent liver resection from October 2005 to May 2006. Control liver specimens
      were seven non-primary liver cancers. A conserved probe representing 100%
      sequence homology was used as a reference for O. viverrini-specific probe. Five
      of six tumors (83%) and all six normal tissues from CCA group; and seven of
      twelve tumors (58%) and ten of twelve normal tissues (83%) from HCC group were
      found to have O. viverrini DNA. The O. viverrini DNA detection among HCC and CCA
      patients were not associated (p=0.193; 90%CI). This RT-PCR will be a useful tool
      for investigating the relationship between cancer type and presence of the
      parasite and also for conducting epidemiological surveys.

PMID- 18329642
TI  - Evaluation of autofluorescence colonoscopy for the detection and diagnosis of
      colonic polyps.
AB  - BACKGROUND: Colorectal cancer is the second most common cause of death in the
      United Kingdom. Most cancers are believed to arise within preexisting adenomas.
      Although colorectal adenomas have a clear neoplastic potential, hyperplastic
      polyps do not. It, therefore, would be helpful to be able to differentiate
      between different polyps at a colonoscopy. Autofluorescence (AF) endoscopy has
      been developed to enhance conventional white light (WL) endoscopy in the
      diagnosis of GI lesions. OBJECTIVE: The aim of the present study was to evaluate
      whether AF colonoscopy can facilitate endoscopic detection and differentiation of
      colorectal polyps. DESIGN: Patients were invited to attend for colonic assessment
      with both AF and WL endoscopy. AF readings, pictures, and biopsy specimens were
      taken of any visible pathology and of any high AF areas. SETTING: Gartnavel
      General Hospital, Glasgow, U.K. PATIENTS: A total of 107 patients were assessed.
      INTERVENTION: Each patient was assessed with AF and WL colonoscopy. MAIN OUTCOME
      MEASUREMENTS: An AF intensity ratio (AIR) was calculated for each polyp (ratio of
      direct polyp AF reading/background rectal AF activity). RESULTS: A total of 75
      polyps were detected: 54 adenomatous and 21 hyperplastic polyps. Colorectal
      adenomas had a significantly higher AIR compared with hyperplastic polyps
      (median, interquartile range): adenoma (3.54, 2.54-5.00] versus hyperplastic
      (1.60, 1.30-2.24); P = .0001). When using an AIR with the empirically cutoff
      value of 2.3, AF endoscopy had a sensitivity of 85% and a specificity of 81% at
      distinguishing adenomatous polyps from hyperplastic polyps. CONCLUSIONS: AF
      colonoscopy may be a valuable tool for the visual distinction between adenomatous
      and hyperplastic polyps.

PMID- 18329643
TI  - GPR54 and rGnRH I gene expression during the onset of puberty in Nile tilapia.
AB  - The Kiss1/GPR54 system has recently been shown to play a key role in the onset of
      puberty in mammals. Growing evidence suggests that this system is also conserved
      across vertebrates although very few studies so far have been performed in lower
      vertebrates. The aims of this study were firstly in the teleost Nile tilapia to
      screen tissues for GPR54 expression levels, secondly to measure the expression
      patterns of GPR54 and GnRH I receptor (rGnRH I) in whole brains during the onset
      of puberty and finally to determine the effects of continuous illumination (LL)
      on receptor expression levels. Results confirmed that GPR54 was predominantly
      expressed in the brain and pituitary of adult tilapia. Furthermore, a significant
      increase of GPR54 gene expression was found in tilapia brains at 11 weeks post
      hatch (wph) followed by rGnRH I at 13 wph just prior to the histological
      observation of vitellogenic oocytes and active spermatogenesis in ova and testes
      at 17 wph. These results suggest a correlation between the increase of GPR54
      expression in the brain and the onset of puberty. Finally, a significant effect
      of LL was observed on GPR54 expression levels which were characterized by a
      delayed surge with significantly lower levels than those of control fish. The
      current study not only suggests a link between the Kiss1/GPR54 system and the
      onset of puberty in a tropical batch spawning teleost that would be a highly
      conserved feature across vertebrates but also that the transcriptional mechanisms
      regulating GPR54 expression could be directly or indirectly influenced by light.

PMID- 18329644
TI  - Biological effects of insulin on murine melanoma cells and fish erythrophoroma
      cells: a comparative study.
AB  - Insulin is the hormone that plays an essential role in metabolism and mitosis of
      normal and tumor cells, exerting its pleiotropic effects through binding to
      specific membrane receptors and promoting the phosphorylation of tyrosine
      residues of the receptor itself and of other components of the signaling pathway.
      The aim of this study was to investigate the effects of insulin on melanogenesis
      and cell growth in three different cell lines: the goldfish GEM-81 erythrophoroma
      cells (undifferentiated and differentiated with 1.5% dimethylsulfoxide-DMSO), and
      the murine B16F10 and Cloudman S91 melanoma cells. Undifferentiated GEM-81 and
      B16F10 cells responded to insulin with a small increase of cell proliferation,
      whereas S91 cells responded with a decrease of growth. In the two mammalian cell
      lines, and in DMSO-differentiated GEM-81 cells, the hormone strongly inhibited
      melanogenesis, by decreasing tyrosinase activity. In undifferentiated GEM-81
      cells, insulin had no effect on tyrosinase activity. An increase in the tyrosine
      phosphorylation status of pp185 (insulin receptor substrate 1 and 2 -- IRS-1/2)
      phosphorylation degree was observed in S91 mouse melanoma and in differentiated
      GEM-81 erythrophoroma cells, suggesting that this specific protein was maintained
      during transformation process and participates in insulin signaling. Our results
      imply an ancient and diverse history of the insulin signaling system in
      vertebrate pigment cells.

PMID- 18329645
TI  - Circadian pattern of total and free corticosterone concentrations, corticosteroid
      binding globulin, and physical activity in mice selectively bred for high
      voluntary wheel-running behavior.
AB  - In vertebrates, baseline glucocorticoid concentrations vary predictably on a diel
      basis, usually peaking shortly before the onset of activity. Presumably,
      circadian patterns in glucocorticoid secretion have evolved to match predictable
      rises in energetic need. In mice from lines selectively bred for high voluntary
      wheel-running, previous studies have reported that baseline plasma corticosterone
      concentrations at two different times during the photophase are elevated twofold
      above those of non-selected control lines. Here, we tested the hypothesis that
      the elevated daytime corticosterone levels could be explained by a shift in the
      circadian pattern of corticosterone levels. We measured baseline total plasma
      corticosterone levels, corticosteroid-binding globulin (CBG) capacity, and
      calculated free corticosterone levels (corticosterone not bound to corticosteroid
      binding globulin and potentially biologically active) at six points during the 24
      hour cycle in males on a 12:12 photoperiod. We also examined the daily pattern of
      both wheel-running and home-cage activity. Based on combined analysis of all six
      points, the circadian pattern of total corticosterone, corticosteroid-binding
      globulin, and free corticosterone levels did not significantly differ between
      high-runner and control mice (linetype * time interaction P=0.56, 0.45, and 0.55,
      respectively); however, all varied with time (all P<0.0001) and mice from the
      selected lines had significantly elevated total (P=0.0125) and free (P=0.0140)
      corticosterone, with no difference in CBG binding capacity (P=0.77). All mice
      were active primarily during the dark phase, and the factorial increase in
      activity of selected relative to controls lines was 2.33 for total daily wheel
      revolutions and 2.76 for total daily home-cage activity. The onset of the active
      period for both measures of locomotor activity coincided with peak total and free
      corticosterone levels in both selected and control lines. These findings lend
      support to our hypothesis that elevated circulating corticosterone levels have
      evolved as an adaptation to support increased locomotor activity in the selected
      lines.

PMID- 18329646
TI  - The physiological cost of restricted weight bearing.
AB  - BACKGROUND: To identify the energy cost of placing restrictions on weight bearing
      status. METHODS: Measurement of the Physiological cost index (PCI) for 11 healthy
      volunteers carrying out three types of mobilisation over a 100 m course in a
      physiology laboratory: normal walking fully weight bearing (FWB); non-weight
      bearing (NWB) and feather touch weight bearing (FTWB). NWB and FTWB were
      performed using a walking frame for support. FTWB was defined as mobilisation
      with the foot flat, as in normal gait, but with less than 100 N force generated
      through the limb. RESULTS: Both NWB and FTWB developed significantly greater PCI
      than normal walking. There was no physiological cost benefit of FTWB over NWB,
      p=0.67, but FTWB was perceived by all participants to be less tiring.
      CONCLUSIONS: Restricting weight bearing status significantly increases energy
      expenditure; the PCI. FTWB may be a more tolerable form of restricted weight
      bearing, although the PCI does not reflect this perception. These findings should
      be borne in mind when recommending such restrictions in clinical practice and
      encouraging a patient to mobilise early and effectively.

PMID- 18329647
TI  - Quality of life and neuropsychological changes in mild head trauma. Late analysis
      and correlation with S100B protein and cranial CT scan performed at hospital
      admission.
AB  - INTRODUCTION: mild head trauma (MHT) is defined as a transient neurological
      deficit after trauma with a history of impairment or loss of consciousness
      lasting less than 15 min and/or posttraumatic amnesia, and a Glasgow Coma Scale
      between 13 and 15 on hospital admission. We evaluated 50 MHT patients 18 months
      after the trauma, addressing signs and symptoms of post-concussion syndrome,
      quality of life and the presence of anxiety and depression. We correlate those
      findings with the S100B protein levels and cranial CT scan performed at hospital
      admission after the trauma. METHOD: patients were asked to fill out
      questionnaires to assess quality of life (SF36), anxiety and depression (HADS),
      and signs and symptoms of post-concussion syndrome. For the control group, we
      asked the patient's household members, who had no history of head trauma of any
      type, to answer the same questionnaires for comparison. RESULTS: total quality of
      life index for patients with MHT was 58.16 (+/-5), lower than the 73.47 (+/-4)
      presented by the control group. Twenty patients (55.2%) and four (11.1%) controls
      were depressed. Seventeen patients (47.2%) presented anxiety, whereas only eight
      (22.2%) controls were considered anxious. Victims of MHT complained more
      frequently of loss of balance, dry mouth, pain in the arms, loss of memory and
      dizziness than their respective controls (p<0.05). We found no correlation
      between the presence of these signs and symptoms, quality of life, presence of
      anxiety and depression with S100B protein levels or with presence of injury in
      the cranial CT performed at hospital admission. CONCLUSION: MHT is associated
      with a higher incidence of post-concussion syndrome symptoms, lower quality of
      life and anxiety than their respective controls even 18 months after the trauma.

PMID- 18329648
TI  - Predictors of self-assessed physical and mental health of Icelandic nurses:
      results from a national survey.
AB  - BACKGROUND: Recent health care organizational changes have been associated with
      stress and musculoskeletal disorders in nurses. However, studies are lacking on
      what factors are the most important predictors of poor self-assessed health among
      nurses. OBJECTIVES: To describe and identify the self-assessed predictors of
      physical and mental health of nurses. PARTICIPANTS AND DESIGN: A cross-sectional
      design was used with a sample of 394 nurses, drawn from the registry of the
      Icelandic Nurses' Association, representing 17% of the workforce of Icelandic
      nurses. METHODS: Data were collected with a self-administered questionnaire,
      addressing symptoms, illness and treatment, lifestyle and sleep, work and working
      environment, family and quality of family life. Data were analysed according to
      nurses' assessment of their physical and mental health (very good/good; poor/very
      poor) by use of analysis of variance, chi-square and stepwise multiple linear
      regression. RESULTS: 21.7% of participants assessed their physical health as poor
      or very poor and 14.3% assessed their mental health as such. Those who assess
      their physical or mental health poor/very poor, as compared to the others,
      reported more symptoms in general, less regular exercise, as well as more use of
      medication, more visits to physicians, trouble with sleeping, conflicts between
      work and family life, work absence, and they experience their work as more
      strenuous. Experiencing symptoms is an important predictor of both physical and
      mental health of nurses. CONCLUSION: Various factors, including work-, family-
      and socio-cultural environment, play a role in how nurses assesses their health.
      During our present time of nurse shortage it is imperative that the authorities
      take special measures in order to improve the work environment of nurses.

PMID- 18329649
TI  - Further testing of a family nursing instrument (FAFHES).
AB  - BACKGROUND: Cardiac illness in one family member affects the well-being and
      health of the whole family. When a family member falls ill, life may change for
      the whole family in many ways. Family members expect nursing staff to provide
      more support when their family situation changes. OBJECTIVES: To describe further
      development and testing of a family nursing instrument for assessing the
      association between social support for the family of an adult cardiac patient and
      family functioning and perceived family health. SETTINGS: The study was conducted
      in two university hospitals and in two central hospitals in Finland. METHODS AND
      PARTICIPANTS: Questionnaires were given to family members of heart patients.
      Patients themselves defined who their closest adult relative was. Data were
      collected from family members of 509 heart patients. RESULTS: Good internal
      reliability in this further testing of a new instrument was demonstrated.
      Principal component analysis (PCA) with varimax rotation was performed in each of
      the three total scales: family functioning, family health and social support. PCA
      supported the previously proposed theoretical framework. A final scale consisted
      of 62 items. All the total scales and subscales had acceptable validity and
      reliability, alpha coefficients ranged from .76 to .98. CONCLUSIONS: The Family
      Functioning, Health and Social Support (FAFHES) provides a reliable and valid
      instrument when the investigator wishes to measure social support associated with
      family functioning and the health of families of heart patients.

PMID- 18329650
TI  - Experimental measurement and quantification of frictional contact between
      biological surfaces experiencing large deformation and slip.
AB  - Interactions between contacting biological surfaces may play significant roles in
      physiological and pathological processes. Theoretical models have described some
      special cases of contact, using one or more simplifying assumptions. Experimental
      quantification of contact could help to validate theoretical analyses. The
      objective of this study was to develop a general mathematical approach describing
      the dynamics of deformation and relative surface motion between contacting bodies
      and to implement this approach to describe the contact between two experimentally
      tracked tissue surfaces. A theoretical formulation (in 2-D and 3-D) of contact
      using the movement of discrete tissue markers is described. The method was
      validated using theoretically generated 3-D datasets, with <1% error for a wide
      range of parameters. The method was applied to the contact loading of opposing
      articular cartilage tissues, where displacements of cell nuclei were tracked
      optically and used to quantify the movements and deformations of the surfaces.
      Compared to tissues with matched material properties, tissues with mismatched
      material properties exhibited increased disparities in lateral expansion and
      relative motion (sliding) between the contacting surfaces.

PMID- 18329651
TI  - Large-volume methacrylate monolith for plasmid purification. Process engineering
      approach to synthesis and application.
AB  - The extent of exothermicity associated with the construction of large-volume
      methacrylate monolithic columns has somewhat obstructed the realisation of large
      scale rapid biomolecule purification especially for plasmid-based products which
      have proven to herald future trends in biotechnology. A novel synthesis technique
      via a heat expulsion mechanism was employed to prepare a 40 mL methacrylate
      monolith with a homogeneous radial pore structure along its thickness. Radial
      temperature gradient was recorded to be only 1.8 degrees C. Maximum radial
      temperature recorded at the centre of the monolith was 62.3 degrees C, which was
      only 2.3 degrees C higher than the actual polymerisation temperature. Pore
      characterisation of the monolithic polymer showed unimodal pore size
      distributions at different radial positions with an identical modal pore size of
      400 nm. Chromatographic characterisation of the polymer after functionalisation
      with amino groups displayed a persistent dynamic binding capacity of 15.5 mg of
      plasmid DNA/mL. The maximum pressure drop recorded was only 0.12 MPa at a flow
      rate of 10 mL/min. The polymer demonstrated rapid separation ability by
      fractionating Escherichia coli DH5alpha-pUC19 clarified lysate in only 3 min
      after loading. The plasmid sample collected after the fast purification process
      was tested to be a homogeneous supercoiled plasmid with DNA electrophoresis and
      restriction analysis.

PMID- 18329652
TI  - Extraction of formic and acetic acids from aqueous solution by dynamic headspace
      needle trap extraction temperature and pH optimization.
AB  - A combined method of dynamic headspace-needle trap sample preparation and gas
      chromatography for the determination of formic and acetic acids in aqueous
      solution was developed in this study. A needle extraction device coupled with a
      gas aspirating pump was intended to perform sampling and preconcentration of
      target compounds from aqueous sample before gas chromatographic analysis. The
      needle trap extraction (NTE) technique allows for the successful sampling of
      short chain fatty acids under dynamic conditions while keeping the headspace (HS)
      volume constant. Two important parameters, including extraction temperature and
      effect of acidification, have been optimized and evaluated using the needle trap
      device. The method detection limits for the compounds estimated were 87.2microg/L
      for acetic acid and 234.8microg/L for formic acid in spite of the low flame
      ionization detection response for formic acid and its low Henry's law constant in
      aqueous solution. Precision was determined based on the two real samples and
      ranged between 4.7 and 10.7%. The validated headspace-needle trap extraction
      method was also successfully applied to several environmental samples.

PMID- 18329653
TI  - Automated on-line in-tube solid-phase microextraction-assisted derivatization
      coupled to liquid chromatography for quantifying residual dimethylamine in
      cationic polymers.
AB  - A method for the analysis of dimethylamine (DMA) by automated in-tube solid-phase
      microextraction (IT-SPME)-supported chemical derivatization coupled with high
      performance liquid chromatography was developed. Extraction, derivatization and
      desorption were studied by using a capillary coated with 95% polydimethylsiloxane
      and 5% polydiphenylsiloxane. Solution derivatization and automated IT-SPME
      derivatization using 9-fluorenylmethyl chloroformate (FMOC) were compared. The
      proposed procedure provided adequate linearity, accuracy and precision in the 0.2
      2.0 microg/mL concentration interval, and the limit of detection (LOD) was 50
      ng/mL. The main advantages of the proposed procedure are: (i) no off-line sample
      manipulation, (ii) rapidity, as the total analysis time is about 10 min, (iii)
      specificity for the samples assayed, (iv) minimal consumption of FMOC reagent and
      (v) minimal residues. Therefore, the proposed method is an environmental-friendly
      and cost-effective alternative for the control of residual DMA in polymeric
      cationic surfactants used like flocculants in water treatment.

PMID- 18329654
TI  - Differences between propane in nitrogen versus air matrix analyzed using gas
      chromatography with flame-ionization detection.
AB  - New US Federal low-level automobile emission requirements, such as Zero Level
      Emission Vehicle (ZLEV), for hydrocarbons and other species have resulted in
      manufacturers need for new certified reference materials. The new emission
      requirement for hydrocarbons requires the use, by automobile manufacturing
      testing facilities, of 100 nmol/mol (ppb) propane in air gas standard. Emission
      measurement instruments are required, by Federal law, to be calibrated with the
      US National Institute of Standards and Technology (NIST) traceable reference
      materials. A NIST Standard Reference Material (SRM) containing 100 nmol/mol
      propane has been developed. During the development of this SRM a critical
      question arose as to the matrix of the primary propane standards. The automobile
      companies make their measurements using total hydrocarbon analyzers with flame
      ionization detectors which integrate all hydrocarbons in a sample. NIST uses gas
      chromatography/flame-ionization detection (GC/FID) with a column to separate all
      components. Since the SRM mixtures were in air, the question as to the effect of
      oxygen on the detector arose. To investigate this effect, two suites of propane
      primary standards were developed: one in air and the other in nitrogen. The two
      suites of primary standards were analyzed using NIST methods, and the
      concentration of propane in an air mixture was determined. The results show that
      there was a difference of 0.63% in the propane concentration determined versus
      air and nitrogen suites.

PMID- 18329655
TI  - Determination of ivermectin and transformation products in environmental waters
      using hollow fibre-supported liquid membrane extraction and liquid chromatography
      mass spectrometry/mass spectrometry.
AB  - A simple and easy-to-use extraction method for aqueous samples based on hollow
      fibre-supported liquid membrane (HF-SLM) followed by liquid chromatography-mass
      spectrometry/mass spectrometry (LC-MS/MS) was developed to determine ivermectin
      and transformation products, the monosaccharide (TP1) and the aglycon of
      ivermectin (TP2). The proposed method attained enrichment factors up to 80, after
      optimising parameters, such as fibre length, organic solvent, stirring speed,
      salt level, pH in samples/fibre, extraction time and fibre emptying technique.
      Method validation with tap and lake water samples provided good linearity and
      detection limits of 0.2, 1.6 and 0.9 microg/l for ivermectin, TP1 and TP2 in lake
      water with RSD below 15%.

PMID- 18329656
TI  - Constitutive modeling of contact angle hysteresis.
AB  - We introduce a phase field model of wetting of surfaces by sessile drops. The
      theory uses a two-dimensional non-conserved phase field variable to parametrize
      the Gibbs free energy of the three-dimensional system. Contact line tension and
      contact angle hysteresis arise from the gradient term in the free energy and the
      kinetic coefficient respectively. A significant advantage of this approach is in
      the constitutive specification of hysteresis. The advancing and receding angles
      of a surface, the liquid-vapor interfacial energy and three-phase line tension
      are the only required constitutive inputs to the model. We first simulate
      hysteresis on a smooth chemically homogeneous surface using this theory. Next we
      show that it is possible to study heterogeneous surfaces whose component surfaces
      are themselves hysteretic. We use this theory to examine the wetting of a surface
      containing a circular heterogeneous island. The contact angle for this case is
      found to be determined solely by the material properties at the contact line in
      accord with recent experimental data.

PMID- 18329657
TI  - Microstructure and structural transition in microemulsions stabilized by
      aldonamide-type surfactants.
AB  - Significant efforts were undertaken to characterize the microstructure and
      structural properties of water-in-oil (w/o), oil-in-water (o/w), and bicontinuous
      (bc) microemulsions composed of N-alkyl-N-methylgluconamides (n-alkyl = n
      C(12)H(25), n-C(14)H(29), n-C(16)H(33)) and n-alcohols (ethanol, n-propanol, n
      butanol) or iso-alcohols (iso-propanol, iso-butanol) as cosurfactants, as well as
      iso-octane and water. The internal structure of so created four-component system
      was elucidated by means of an analysis of isotropic area magnitudes in phase
      diagrams and conductivity measurements. Dynamic light scattering (DLS)
      measurements provided the microemulsion size and polydispersity. Polarity and
      viscosity of microemulsion microenvironment were acquired by means of electron
      paramagnetic resonance (EPR), UV-vis absorption spectroscopy (in the case of w/o
      droplets), and steady-state fluorescence (SSF) (in the case of o/w droplets). The
      results show that both the surfactant and the cosurfactant types affect the shape
      and extent of microemulsions. The size of droplets depends strongly on the type
      of examined microemulsion and the type of cosurfactant (linear or brunched) but
      is almost independent of the length of the surfactant alkyl chain. The size of
      microemulsion droplets ranges from 8.1 to 22.6 nm and from 3.7 to 14.3 nm
      respectively, for o/w and o/w microemulsions, making them good candidates for
      both template-based reactions and household components solubilizing media.

PMID- 18329658
TI  - Development of a microemulsion-based process for synthesis of cobalt (Co) and
      cobalt oxide (Co3O4) nanoparticles from submicrometer rods of cobalt oxalate.
AB  - Rod-shaped nanostructures of cobalt oxalate dihydrate were synthesized at room
      temperature by the microemulsion (reverse micellar) route. These rods are highly
      uniform in length and can be modified with temperature (from approximately 6.5
      microm at 50 degrees C to approximately 2.5 microm at 150 degrees C) while
      keeping the diameter nearly constant (200-250 nm). Thermal decomposition of these
      rods in a controlled atmosphere (air and H(2)) leads to nanoparticles of
      Co(3)O(4) and Co, respectively, while in a helium atmosphere a mixture of Co and
      CoO nanoparticles is obtained. Co(3)O(4) nanoparticles (approximately 35 nm) were
      slightly agglomerated, while Co nanoparticles were monodispersed and highly
      uniform (approximately 25 nm). The oxalate rods and Co(3)O(4) nanoparticles show
      an antiferromagnetic ordering at 54 and 35 K, respectively.

PMID- 18329659
TI  - Synthesis of cobalt ferrite core/metallic shell nanoparticles for the development
      of a specific PNA/DNA biosensor.
AB  - Controlled synthesis of cobalt ferrite superparamagnetic nanoparticles covered
      with a gold shell has been achieved by an affinity and trap strategy. Magnetic
      nanoparticles are functionalized with a mixture of amino and thiol groups that
      facilitate the electrostatic attraction and further chemisorption of gold
      nanoparticles, respectively. Using these nanoparticles as seeds, a complete
      coating shell is achieved by gold salt-iterative reduction leading to
      monodisperse water-soluble gold-covered magnetic nanoparticles, with an average
      diameter ranging from 21 to 29 nm. These constitute a versatile platform for
      immobilization of biomolecules via thiol chemistry, which is exemplified by the
      immobilization of peptide nucleic acid (PNA) oligomers that specifically
      hybridize with complementary DNA molecules in solution. Hybridation with DNA
      probes has been measured using Rhodamine 6G fluorescence marker and the detection
      of a single nucleotide mutation has been achieved. These results suggest the PNA
      nanoparticles application as a biosensor for DNA genotyping avoiding commonly
      time-consuming procedures employed.

PMID- 18329660
TI  - Recognition of melting of nanoparticle catalysts with cubically shaped Co3O4
      nanoparticles.
AB  - Cubically shaped cobalt oxide nanoparticle catalysts were used for the first time
      to investigate the melting of the nanoparticle catalysts responsible for the
      synthesis of silica nanocoils at 1050 degrees C and straight nanowires at 1100
      degrees C. Cobalt nanoparticles remained morphologically highly anisotropic after
      the growth of nanocoils at 1050 degrees C, whereas they became predominately
      spherical after straight nanowires were made at 1100 degrees C. These results
      strongly indicated that cobalt nanoparticles responsible for the synthesis of
      straight nanowires were completely molten and that melting occurred to these
      nanoparticles between 1050 and 1100 degrees C.

PMID- 18329661
TI  - Enhancement of the reductive transformation of pentachlorophenol by
      polycarboxylic acids at the iron oxide-water interface.
AB  - The enhancement effect of polycarboxylic acids on reductive dechlorination
      transformation of pentachlorophenol (PCP) reacting with iron oxides was studied
      in anoxic suspension. Batch experiments were performed with three species of iron
      oxides (goethite, lepidocrocite and hematite) and four species of polycarboxylic
      acids (oxalate, citrate, succinate, and tartrate) through anoxic abiotic
      reactors. The chemical analyses and morphological observation from scanning and
      transmission electron microscopy showed that different combinations between
      polycarboxylic acids and iron oxides produced distinct contents of Fe(II)
      polycarboxylic ligand complexes, which significantly enhanced PCP transformation.
      Generation of the surface-bound Fe(II) depended on concentration of
      polycarboxylic acids. The optimal concentration for the enhancement was 2.0 mM
      oxalic acid. The dechlorination mechanism was further demonstrated by generation
      of chloride ions. The results suggest that surface-bound Fe(II) formed on the
      iron oxides surface appears to be a key factor in enhancing PCP transformation,
      and the mole ratio of oxalate to surface-bound Fe(II) (oxalate/Fe(II)) acted as
      an indicator of the enhancement effect. The enhancement mechanism attributes to
      strong nucleophilic ability and low reductive potential of the equivalent Fe(II)
      polycarboxylate complexes. Therefore, the enhancement effects might be helpful
      for understanding the natural attenuation of reducible organic pollutants at the
      interface of contaminated soil in anoxic condition.

PMID- 18329662
TI  - Synthesis of Cd-free water-soluble ZnSe(1-x)Te(x) nanocrystals with high
      luminescence in the blue region.
AB  - Cd-free core-shell nanocrystals (ZnSe(1-x)Te(x)/ZnS, 0<or=x<or=0.5) emitting in
      the pure blue region were prepared using an aqueous colloidal method followed by
      post-preparative ultraviolet irradiation. The photoluminescence (PL) efficiency
      and peak wavelength were maximized (40%, 448 nm) through a heat treatment of the
      nanocrystals during irradiation in a Zn(2+)-containing thiol solution. Because of
      the small lattice mismatch between ZnSe(1-x)Te(x) and ZnS, post-preparative
      irradiation at high temperature resulted in the formation of a thick ZnS shell
      (ca. 1.6 nm) around the core (ca. 2.2 nm in diameter) without deterioration of PL
      efficiency. Surface substitution of Te by S and size-selective precipitation of
      nanocrystals before ultraviolet irradiation resulted in intense PL. Quantum
      mechanical calculations show that the wave function of the electron of the
      exciton in the Te-containing core extends well into the ZnS shell. The
      calculations also reveal that a thick shell can confine the electrons inside the
      particles and thereby improve the PL efficiency and stability against the pH of
      the solution. Nanocrystals that had been post-preparatively irradiated showed
      good stability in solution and in a glass matrix even after months of storage in
      air.

PMID- 18329663
TI  - Design and optimization of a multiplex anti-influenza peptide immunoassay.
AB  - Current flu vaccines are based on killed or attenuated virus vaccines that must
      be altered each year to include the hemagglutinin and neuraminidase genes from a
      strain of virus predicted to predominate in the coming year. A vaccine that could
      protect against multiple strains of influenza A and B would be a major asset in
      the fight against flu-related mortality and morbidity. To support development of
      such a vaccine, we have developed a Flu Multiplex Assay based on a Luminex
      platform to assess serum antibody levels to two conserved peptides derived from
      influenza A (M2 protein) and influenza B (hemagglutinin protein). The peptides
      were synthesized with a biotin label and subsequently coupled to two different
      LumAvidin microspheres. We then tested various sera against both types of peptide
      in the multiplex assay format. The data show that sera from Rhesus macaques
      immunized with a single peptide react only with the homologous peptide while
      Rhesus macaques immunized with both peptides respond well to both peptides.
      Additionally, we were able to specifically compete reactivity to both peptides.
      We have tested serial bleeds from 100 pediatric patients at ages ranging from 16
      to 56 weeks as well as single bleeds from over 100 healthy adults. No overall
      trend in titer relative to pediatric age was detected. Both demographics
      exhibited a minimal response to either the A/M2 or B/HA0 peptides. However, the
      average titer for the pediatric serum samples was significantly lower than that
      found in the adult population. The adult population exhibited a higher prevalence
      of low reactive samples. Assay reagents and parameters have been optimized and
      the assay is shown to be repeatable and robust. The assay will be used to support
      clinical vaccine trials of a bivalent peptide vaccine.

PMID- 18329664
TI  - In vitro neutralization of equid herpesvirus 1 mediated by recombinant
      antibodies.
AB  - A phage antibody display library of single chain fragment variables (scFv) was
      applied to develop anti-equid herpesvirus-1 (EHV-1) glycoprotein D (gD)
      neutralizing antibodies. To enrich for specific scFvs, the phage antibody library
      was panned against epitope derived from the N-terminal part of EHV-1 gD. Unique
      clones were differentiated by BstNI fingerprinting and further characterized by
      sequencing and immunoreactivity. The neutralizing effect of each clone was
      assessed by plaque reduction assay. Three clones with neutralizing effect were
      isolated.

PMID- 18329665
TI  - Expressed sequence tags from the red imported fire ant, Solenopsis invicta:
      annotation and utilization for discovery of viruses.
AB  - An expression library was created and 2304 clones sequenced from a monogyne
      colony of Solenopsis invicta. The primary intention of the project was to utilize
      homologous gene identification to facilitate discovery of viruses infecting this
      ant pest that could potentially be used in pest management. Additional genes were
      identified from the ant host and associated pathogens that serve as an important
      resource for studying these organisms. After assembly and removal of
      mitochondrial and poor quality sequences, 1054 unique sequences were yielded and
      deposited into the GenBank database under Accession Nos. EH412746 through
      EH413799. At least nine expressed sequence tags (ESTs) were identified as
      possessing microsatellite motifs and 15 ESTs exhibited significant homology with
      microsporidian genes. These sequences most likely originated from Thelohania
      solenopsae, a well-characterized microsporidian that infects S. invicta. Six ESTs
      exhibited significant homology with single-stranded RNA viruses (3B4, 3F6, 11F1,
      12G12, 14D5, and 24C10). Subsequent analysis of these putative viral ESTs
      revealed that 3B4 was most likely a ribosomal gene of S. invicta, 11F1 was a
      single-stranded RNA (ssRNA) virus contaminant introduced into the colony from the
      cricket food source, 12G12 appeared to be a plant-infecting tenuivirus also
      introduced into the colony as a field contaminant, and 3F6, 14D5, and 24C10 were
      all from a unique ssRNA virus found to infect S. invicta. The sequencing project
      illustrates the utility of this method for discovery of viruses and pathogens
      that may otherwise go undiscovered.

PMID- 18329666
TI  - Structures and solution properties of two novel periplasmic sensor domains with c
      type heme from chemotaxis proteins of Geobacter sulfurreducens: implications for
      signal transduction.
AB  - Periplasmic sensor domains from two methyl-accepting chemotaxis proteins from
      Geobacter sulfurreducens (encoded by genes GSU0935 and GSU0582) were expressed in
      Escherichia coli. The sensor domains were isolated, purified, characterized in
      solution, and their crystal structures were determined. In the crystal, both
      sensor domains form swapped dimers and show a PAS-type fold. The swapped segment
      consists of two helices of about 45 residues at the N terminus with the hemes
      located between the two monomers. In the case of the GSU0582 sensor, the dimer
      contains a crystallographic 2-fold symmetry and the heme is coordinated by an
      axial His and a water molecule. In the case of the GSU0935 sensor, the crystals
      contain a non-crystallographic dimer, and surprisingly, the coordination of the
      heme in each monomer is different; monomer A heme has His-Met ligation and
      monomer B heme has His-water ligation as found in the GSU0582 sensor. The
      structures of these sensor domains are the first structures of PAS domains
      containing covalently bound heme. Optical absorption, electron paramagnetic
      resonance and NMR spectroscopy have revealed that the heme groups of both sensor
      domains are high-spin and low-spin in the oxidized and reduced forms,
      respectively, and that the spin-state interconversion involves a heme axial
      ligand replacement. Both sensor domains bind NO in their ferric and ferrous forms
      but bind CO only in the reduced form. The binding of both NO and CO occurs via an
      axial ligand exchange process, and is fully reversible. The reduction potentials
      of the sensor domains differ by 95 mV (-156 mV and -251 mV for sensors GSU0582
      and GSU0935, respectively). The swapped dimerization of these sensor domains and
      redox-linked ligand switch might be related to the mechanism of signal
      transduction by these chemotaxis proteins.

PMID- 18329667
TI  - Crystal structure of Lsm3 octamer from Saccharomyces cerevisiae: implications for
      Lsm ring organisation and recruitment.
AB  - Sm and Sm-like (Lsm) proteins are core components of the ribonucleoprotein
      complexes essential to key nucleic acid processing events within the eukaryotic
      cell. They assemble as polyprotein ring scaffolds that have the capacity to bind
      RNA substrates and other necessary protein factors. The crystal structure of
      yeast Lsm3 reveals a new organisation of the L/Sm beta-propeller ring, containing
      eight protein subunits. Little distortion of the characteristic L/Sm fold is
      required to form the octamer, indicating that the eukaryotic Lsm ring may be more
      pliable than previously thought. The homomeric Lsm3 octamer is found to
      successfully recruit Lsm6, Lsm2 and Lsm5 directly from yeast lysate. Our crystal
      structure shows the C-terminal tail of each Lsm3 subunit to be engaged in
      connections across rings through specific beta-sheet interactions with elongated
      loops protruding from neighbouring octamers. While these loops are of distinct
      length for each Lsm protein and generally comprise low-complexity polar
      sequences, several Lsm C-termini comprise hydrophobic sequences suitable for beta
      sheet interactions. The Lsm3 structure thus provides evidence for protein-protein
      interactions likely utilised by the highly variable Lsm loops and termini in the
      recruitment of RNA processing factors to mixed Lsm ring scaffolds. Our
      coordinates also provide updated homology models for the active Lsm[1-7] and
      Lsm[2-8] heptameric rings.

PMID- 18329668
TI  - Positive association of the PDE4B (phosphodiesterase 4B) gene with schizophrenia
      in the Japanese population.
AB  - The phosphodiesterase 4B (PDE4B) gene is located at 1p31, a susceptibility region
      for schizophrenia (SZ). Moreover, PDE4B interacts with DISC1, which is a known
      genetic risk factor for SZ. Recently, it was reported that the PDE4B gene is
      associated with SZ in Caucasian and African American populations. In this study,
      case-controlled association analyses were performed in the Japanese population to
      determine if the PDE4B gene is implicated in SZ. Thirteen single nucleotide
      polymorphisms (SNPs) were analyzed in 444 schizophrenic patients and 452 control
      subjects. Three SNPs (rs2180335, rs910694 and rs472952) were significantly
      associated with SZ after applying multiple test correction (p=0.039, 0.004 and
      0.028). In addition, a significant association was found between specific
      haplotypes (rs2180335 and rs910694) and SZ (permutation p=0.001). Our result
      suggests that variations at the PDE4B locus may play a significant role in the
      etiology of SZ in the Japanese population.

PMID- 18329669
TI  - Endothelium-independent vasodilation effect of di- and tri-peptides in thoracic
      aorta of Sprague-Dawley rats.
AB  - The goal of this study was to elucidate the structure-activity relationship for
      vasodilating peptides and their underlying mechanism. In this study, we
      synthesized 62 di- and tri-peptides having aromatic amino acid residues (Tyr, Trp
      and Phe). Among them, only 4 peptides (HW, WH, WL and WV) evoked an apparent
      vasodilating effect in 50 mM KCl-contracted aortic rings in the descending order
      of WH>HW>WL>WV; WH showed the vasodilating activity with an EC50 of 3.4 mM.
      Within our experimental results, it seems likely that Trp residue at the N
      terminal would play a role in eliciting vasodilating effect. No appearance of
      vasodilating effect for stereoisomers of WH with D-configuration revealed that
      the vessel would recognize the L-configuration of WH. The presence of angiotensin
      I-converting enzyme (ACE) inhibitor (50 nM enalaprilat) did not affect the WH
      induced vasodilating effect, though WH showed a slight ACE inhibitory activity
      (IC50: 93 microM). The effect was also observed in the endothelium-denuded aortic
      rings. In contrast, WH provoked a significant displacement to the right in the
      vasodilating curve in the presence of 30 nM verapamil, while no shift was
      observed in the presence of 2.5 nM nifedipine. These results indicate that WH, a
      vasodilating di-peptide, would exert a vasodilation via the suppression of Ca2+
      influx into KCl-induced depolarized aortic rings. The present study also suggests
      that the binding site of WH to the Ca2+ channel may be competitive to that of
      phenylalkylamine-type voltage-gated L-type Ca2+ channel blocker.

PMID- 18329670
TI  - On the role of tyrosine and peripheral metabolism in 3,4
      methylenedioxymethamphetamine-induced serotonin neurotoxicity in rats.
AB  - The mechanisms underlying 3,4-methylenedioxymethamphetamine (MDMA)-induced
      serotonergic (5-HT) toxicity remain unclear. It has been suggested that MDMA
      depletes 5-HT by increasing brain tyrosine levels, which via non-enzymatic
      hydroxylation leads to DA-derived free radical formation. Because this hypothesis
      assumes the pre-existence of hydroxyl radicals, we hypothesized that MDMA
      metabolism into pro-oxidant compounds is the limiting step in this process. Acute
      hyperthermia, plasma tyrosine levels and concentrations of MDMA and its main
      metabolites were higher after a toxic (15 mg/kg i.p.) vs. a non-toxic dose of
      MDMA (7.5mg/kg i.p.). The administration of a non-toxic dose of MDMA in
      combination with l-tyrosine (0.2 mmol/kg i.p.) produced a similar increase in
      serum tyrosine levels to those found after a toxic dose of MDMA; however, brain 5
      HT content remained unchanged. The non-toxic dose of MDMA combined with a high
      dose of tyrosine (0.5 mmol/kg i.p.), caused long-term 5-HT depletions in rats
      treated at 21.5 degrees C but not in those treated at 15 degrees C, conditions
      known to decrease MDMA metabolism. Furthermore, striatal perfusion of MDMA (100
      microM for 5h) combined with tyrosine (0.5 mmol/kg i.p.) in hyperthermic rats did
      not cause 5-HT depletions. By contrast, rats treated with the non-toxic dose of
      MDMA under heating conditions or combined with entacapone or acivicin, which
      interfere with MDMA metabolism or increase brain MDMA metabolite availability
      respectively, showed significant reductions of brain 5-HT content. Altogether,
      these data indicate that although tyrosine may contribute to MDMA-induced
      toxicity, MDMA metabolism appears to be the limiting step.

PMID- 18329671
TI  - An fMRI study of theory of mind in schizophrenic patients with "passivity"
      symptoms.
AB  - Several studies have shown that patients with schizophrenia underactivate brain
      regions involved in theory of mind relative to controls during functional brain
      imaging. However, in most studies the samples were fairly heterogeneous in terms
      of clinical symptomatology. We examined a group of nine patients with first
      episode or recurrent episodes, who clinically presented with predominant
      "passivity" symptoms such as third-person auditory hallucinations or delusion of
      control, using a cartoon-based theory of mind task and compared activation
      patterns with a group of 13 healthy controls. All patients responded well to
      antipsychotic treatment and were only mildly symptomatic at the time of testing.
      The patient group showed significantly less activation of the right anterior
      cingulate cortex (ACC) and right insula compared with controls, but greater
      activation in dorsal areas of the medial prefrontal cortex, right temporal areas
      and left temporo-parietal junction. Patients with schizophrenia with predominant
      "passivity" symptoms and good response to antipsychotic treatment show a markedly
      diverging pattern of brain activation during theory of mind task performance
      compared with healthy controls. These findings suggest abnormal activation of
      those brain areas involved in the evaluation of self-reference during mental
      state attribution.

PMID- 18329672
TI  - Prospective memory and mesial temporal epilepsy associated with hippocampal
      sclerosis.
AB  - Episodic memory impairment is commonly observed in patients with epilepsy
      associated with mesial temporal sclerosis (MTS). Prospective memory (PM) is a set
      cognitive abilities that allow future performance of a present intention, in
      response to time- or event-based evocation cues, that trigger the intended action
      at the appropriate time. PM has not been evaluated in mesial temporal sclerosis.
      We evaluated the role of right and left hippocampal lesions on performance in
      both the retrospective and prospective PM components in patients with epilepsy
      secondary to mesial temporal sclerosis and correlated with performance in
      traditional neuropsychological tests, as well as with self-perception of memory
      impairment. We tested the hypotheses that a hippocampal lesion impacts on the
      prospective components of PM, and that a left-sided lesion had a greater impact
      on performance in the prospective component of PM than a right-sided lesion. We
      evaluated PM in 26 patients with right MTS, 22 left MTS patients, and 26 age
      gender and education matched controls. The prospective component of PM was
      impaired in both patient groups, with both a lesion (patients performed
      significantly worse in the PM battery) and laterality effect (left MTS patients
      performed significantly worse than right MTS patients in the PM battery).
      Performance in the prospective component of the PM battery correlated with long
      term delay performance in episodic verbal memory and self-perception of memory
      impairment in the left MTS group. The retrospective component was impaired in
      left MTS patients. Impaired performance was not accounted for solely by
      depression, anxiety or an antiepileptic drug effect. We conclude that mesial
      temporal lobe structures, including the hippocampus, play an important role in
      both the prospective and retrospective components of PM processes in tasks
      involving long delay intervals.

PMID- 18329673
TI  - Emotional decision-making and its dissociable components in schizophrenia and
      schizoaffective disorder: a behavioural and MRI investigation.
AB  - Cognitive decision-making is known to be deficient, but relatively less is known
      about emotional decision-making in schizophrenia. The Iowa gambling task (IGT) is
      considered a reliable probe of emotional decision-making and believed to reflect
      orbitofrontal cortex (OFC) function. The expectancy-valence model of IGT
      performance implicates three dissociable components, namely, attention to reward,
      memory for past, relative to recent, outcomes and impulsivity in emotional
      decision-making. We examined IGT performance, its three components, and their
      grey matter volume (GMV) correlates in 75 stable patients with schizophrenia,
      relative to 25 healthy individuals. Patients, relative to controls, showed
      impaired IGT performance and poor memory for past, relative to recent, outcomes.
      IGT performance correlated with GMV in the OFC in controls, but not patients.
      There were associations between (a) attention to reward and GMV in the frontal,
      temporal, parietal and striatal regions in controls, and in the temporal and
      thalamic regions in patients, (b) memory for past outcomes and GMV in the
      temporal region in controls, and the frontal and temporal regions in patients,
      and (c) low impulsivity and greater GMV in the frontal, temporal, posterior
      cingulate and occipital regions in controls, and in the frontal, temporal and
      posterior cingulate regions in patients. Most IGT-GMV associations were stronger
      in controls. It is concluded that (i) poor memory, rather than less attention to
      reward or impulsivity, contributes to IGT performance deficit, and (ii) the
      relationship of IGT performance and its components with GMVs especially in the
      frontal and temporal lobes is lost or attenuated in schizophrenia.

PMID- 18329674
TI  - Plant growth regulation activity of steviol and derivatives.
AB  - This work describes the preparation of tetracyclic diterpenoids and determination
      of their plant growth regulator properties. Stevioside (2) was used as starting
      material and the derivatives 13-hydroxy-ent-kaur-16-en-19-oic acid (steviol, 3),
      ent-7alpha,13-dihydroxy-kaur-16-en-19-oic acid (4), 13-hydroxy, ent-kaur-16,17
      epoxi-19-oic acid (steviol epoxide, 5), 17-hydroxy-16-ketobayeran-19-oic acid (17
      hydroxyisosteviol, 6), 17-hydroxy-16-hydroxyiminobayeran-19-oic acid (7), 16
      ketobayeran-19-oic acid (isosteviol, 9), 16,17-dihydroxybeyeran-19-oic acid (8),
      and 16-hydroxyiminobayeran-19-oic acid (isosteviol oxime, 10) were obtained by
      simple chemical procedures. Another derivative, ent-7alpha,13-dihydroxycaur-15-en
      19-oic acid (4), was obtained by biotransformation of steviol (3) by Penicillium
      citrinum. In order to determine the plant growth regulator activity the compounds
      were submitted to the lettuce hypocotyl and barley aleurone bioassays. All
      compounds showed significant activities in both bioassays. Steviol (3) and
      isosteviol (9) were also tested in field-grown grapes resulting in an increase in
      berry weight and size.

PMID- 18329675
TI  - Triterpenoidal saponins from Hydrocotyle sibthorpioides.
AB  - Oleanane-type triterpenoidal saponins, hydrocosisaponins A-F (1-6), along with a
      known saponin, hydrocotyloside VII (7), were isolated from Hydrocotyle
      sibthorpioides. Their structures were established on the basis of spectroscopic
      analyses including NMR spectroscopic techniques ((13)C, (1)H, COSY, HMQC, HMBC,
      TOCSY and NOESY). Biological evaluation established that saponins possessing four
      sugar units (three d-glucoses and one l-arabinose) (4-7) exhibited moderate
      cytotoxicity against KB, Daoy and WiDr human tumor cell lines.

PMID- 18329676
TI  - Triterpenoid saponins from the fruits and galls of Sapindus mukorossi.
AB  - Six saponins, sapinmusaponin K (1) [hederagenin-3-O-(3-O-acetyl-alpha-L
      arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside], sapinmusaponin L (2) [hederagenin-3-O-(4-O-acetyl-alpha-L
      arabinopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabino
      pyranoside], sapinmusaponin M (3) [hederagenin-3-O-(2,3-O-diacetyl-beta-D
      xylopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside], sapinmusaponin N (4) [hederagenin-3-O-(2,4-O-diacetyl-beta-D
      xylopyranosyl)-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L
      arabinopyranoside], sapinmusaponin O (5) [3,7,20(S)-trihydroxydammar-24-ene-3-O
      alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside], and sapinmusaponin P (6)
      [3,7,20(R)-trihydroxydammar-24-ene-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-d
      glucopyranoside], along with seven known saponins (7-13), were isolated from
      fruits and the galls of Sapindus mukorossi. Their structures were elucidated by
      1D and 2D NMR spectroscopic techniques and acid hydrolysis. Biological evaluation
      indicated that saponins 1-4 and 7-13 showed moderate cytotoxicity against several
      human tumor cell lines.

PMID- 18329677
TI  - Seasonal changes of fatty acid composition and thermotropic behavior of polar
      lipids from marine macrophytes.
AB  - Major glyco- and phospholipids as well as betaine lipid 1,2-diacylglycero-O-4'
      (N,N,N-tri-methyl)-homoserine (DGTS) were isolated from five species of marine
      macrophytes harvested in the Sea of Japan in summer and winter at seawater
      temperatures of 20-23 and 3 degrees C, respectively. GC and DSC analysis of
      lipids revealed a common increase of ratio between n-3 and n-6 polyunsaturated
      fatty acids (PUFAs) of polar lipids from summer to winter despite their
      chemotaxonomically different fatty acid (FA) composition. Especially, high level
      of different n-3 PUFAs was observed in galactolipids in winter. However, the rise
      in FA unsaturation did not result in the lowering of peak maximum temperature of
      phase transition of photosynthetic lipids (glycolipids and phosphatidylglycerol
      (PG)) in contrast to non-photosynthetic ones [phosphatidylcholine (PC) and
      phosphatidylethanolamine (PE)]. Different thermotropic behavior of these lipid
      groups was accompanied by higher content of n-6 PUFAs from the sum of n-6 and n-3
      PUFAs in PC and PE compared with glycolipids and PG in both seasons. Seasonal
      changes of DSC transitions and FA composition of DGTS studied for the first time
      were similar to PC and PE. Thermograms of all polar lipids were characterized by
      complex profiles and located in a wide temperature range between -130 and 80
      degrees C, while the most evident phase separation occurred in PGs in both
      seasons. Polarizing microscopy combined with DSC has shown that the liquid
      crystal - isotropic melt transitions of polar lipids from marine macrophytes
      began from 10 to 30 degrees C mostly, which can cause the thermal sensitivity of
      plants to superoptimal temperatures in their environment.

PMID- 18329678
TI  - Antioxidant phenylpropanoid glycosides from Smilax bracteata.
AB  - From the ethanolic extract of Smilax bracteata, six phenylpropanoid glycosides,
      smilasides G-L (1-6), along with four known phenylpropanoid compounds,
      helonioside A, helonioside B, smilaside E, and (1-p-O-coumaroyl-6-O-feruroyl)
      beta-d-fructofuranosyl-alpha-d-glucopyranoside, and fourteen known phenolic
      compounds were isolated. Their structures were elucidated on the basis of
      spectroscopic analyses. Moreover, 1-6 exhibited moderate scavenging activities
      against DPPH radicals.

PMID- 18329679
TI  - Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone
      receptors.
AB  - Confocal microscopy and cell fractionation studies have revealed the residence of
      nuclear thyroid hormone receptors (TR) in cytoplasm. Treatment of cells with the
      hormone (L-thyroxine or 3,5,3'-triiodo-L-thyronine, T(3)) results in shuttling of
      TR into the nuclear compartment. Confocal microscopy has also disclosed that TR
      in the nuclear compartment is redistributed in response to exposure of cells to
      iodothyronine. The TRbeta1 isoform may be found in cytoplasm of thyroid hormone
      treated cells complexed with other proteins, such as mitogen-activated protein
      kinase (MAPK), the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI 3
      K) and nuclear receptor coactivators. Formation of such complexes may facilitate
      nuclear import of TR and initiate specific gene transcription (PI 3-K) or cell
      proliferation (MAPK). Nuclear retention of TRalpha1 is also increased by T(3). It
      is not clear that iodothyronines have primary effects on nuclear export of TRs.
      Thyroid hormone may also increase cytoplasm-to-nucleus partitioning of p53 and
      certain signal-transducing pathway proteins. A monomer derived from the cell
      surface receptor for thyroid hormone on integrin alphavbeta3 that does not share
      homologies with TR may move to the cell nucleus in thyroid hormone-treated cells.
      Because cells in the intact organism are tonically exposed to thyroid hormone,
      the latter is likely to contribute to the basal rate of nuclear import of thyroid
      hormone receptors.

PMID- 18329680
TI  - Mature adipocytes: are there still novel things that we can learn from them?

PMID- 18329681
TI  - Inorganic arsenic exposure affects pain behavior and inflammatory response in
      rat.
AB  - Inorganic arsenic (iAs) contamination of drinking water is a worldwide problem
      associated with an increased risk for the development of various types of cancer
      and noncancerous damage. In vitro studies have suggested that iAs can modulate
      the activity of macrophages producing an over-expression of cyclooxygenase-2 (COX
      2) and resulting in an increase in prostaglandin E(2) (PGE(2)) concentrations in
      endothelial cells. These effects may lead to an in vivo enhancement of
      inflammatory and pain responses. Our aim was to determine the effect of a single
      dose of arsenic or subchronic exposure to arsenic on pain behavior and tissue
      inflammation in rats. Rats were given a single dose of sodium arsenite (0.1, 1
      and 10 mg/kg i.p.) or submitted to subchronic exposure to arsenic added to the
      drinking water for 4 weeks (0.1, 1, 10 and 100 ppm). Inflammatory pain was
      assessed by using the formalin and tail-flick tests, while inflammation was
      evaluated with the carrageenan model. Arsenite did not induce pain or significant
      inflammation by itself. In contrast, arsenite in both single dose administration
      and subchronic exposure increased not only the inflammatory process and the
      underlying hyperalgesic pain, but also induced a decrease in the pain threshold.
      Alterations in pain processing were dependent on the arsenic dose and the length
      of exposure, and the underlying mechanism involved an increased release of local
      PGE(2). These results suggest that inorganic arsenic exposure enhances pain
      perception and exacerbates the pathological state of inflammatory diseases.

PMID- 18329682
TI  - Secretory phospholipase A2 mediates progression of acute liver injury in the
      absence of sufficient cyclooxygenase-2.
AB  - Previous studies have shown that injury initiated by toxicants progresses even
      after most of the toxicant is eliminated from the body. One mechanism of
      progression of injury is the extracellular appearance of hydrolytic enzymes
      following leakage or upon cell lyses. Under normal conditions, after exposure to
      low to moderate doses of toxicants, secretory phospholipase A(2) (sPLA(2)) and
      other hydrolytic enzymes are known to appear in the extracellular spaces in order
      to cleanup the post-necrotic debris in tissues. We tested the hypothesis that
      sPLA(2) contributes to progression of toxicant-initiated liver injury because of
      hydrolysis of membrane phospholipids of hepatocytes in the perinecrotic areas in
      the absence of sufficient cyclooxygenase-2 (COX-2). Male Sprague-Dawley rats were
      administered either a moderately hepatotoxic dose (MD, 2 ml CCl(4)/kg, ip) or a
      highly hepatotoxic dose (HD, 3 ml CCl(4)/kg, ip) of CCl(4). After MD, liver
      sPLA(2) and COX-2 were co-localized in the necrotic and perinecrotic areas and
      their activities in plasma and liver increased before decreasing in tandem with
      liver injury (ALT and histopathology) leading to 100% survival. In contrast,
      after the HD, high extracellular and hepatic sPLA(2) activities were accompanied
      by minimal COX-2 activity and localization in the liver throughout the time
      course. This led to progression of liver injury and 70% mortality. These data
      suggested a destructive role of sPLA(2) in the absence of sufficient COX-2. Time-
      and dose-dependent destruction of hepatocytes by sPLA(2) in isolated hepatocyte
      incubations confirmed the destructive ability of sPLA(2) when present
      extracellularly, suggesting its ability to spread injury in vivo. These findings
      suggest that sPLA(2), secreted for cleanup of necrotic debris upon initiation of
      hepatic necrosis, requires the co-presence of sufficiently induced COX-2 activity
      to prevent the run-away destructive action of sPLA(2) in the absence of the
      tissue protective mechanisms afforded by COX-2 induction.

PMID- 18329683
TI  - A179L, a viral Bcl-2 homologue, targets the core Bcl-2 apoptotic machinery and
      its upstream BH3 activators with selective binding restrictions for Bid and Noxa.
AB  - Several large DNA viruses encode Bcl-2 protein homologues involved in the
      regulation of the cellular apoptosis cascade. This regulation often involves the
      interaction of these viral proteins with diverse cellular Bcl-2 family members.
      We have identified the specific interactions of A179L, an African swine fever
      virus (ASFV) Bcl-2 homologue, with the active forms of the porcine BH3-only Bid
      protein (truncated Bid p13 and p15). Transient expression of ASFV A179L gene in
      Vero cells prevented apoptosis induced by these active forms of Bid protein.
      Interestingly, A179L protein was able to interact, also with the main core Bcl-2
      proapoptotic proteins Bax and Bak, and with several BH3-only proteins with
      selective binding restrictions for full length Bid and Noxa. These results
      suggest a fine regulation for A179L action in the suppression of apoptosis in
      infected cells which is essential for efficient virus replication.

PMID- 18329685
TI  - Aggregation and surface properties of F-specific RNA phages: implication for
      membrane filtration processes.
AB  - We report an experimental investigation of the electrokinetic properties and size
      variations of four F-specific bacteriophages of the types MS2, GA, Qbeta and SP
      (21-30 nm in diameter) over a broad range of pH values (1.5-7.5) and NaNO3
      electrolyte concentrations (1-100 mM). The results obtained by dynamic light
      scattering show that the aggregation of SP and GA particles takes place over the
      whole range of pH and ionic strength conditions examined. For MS2 phages, the
      aggregation of MS2 particles is not observed for pH higher than the isoelectric
      point (pI) and large ionic strengths for which interparticular repulsive
      electrostatic interactions are however expected to be sufficiently screened.
      Aggregation of the MS2 phages, dispersed in 1 and 100 mM electrolyte
      concentration, occurs at pH 4, which basically corresponds to the pI as
      determined by electrophoresis measurements. The Qbeta particles suspended in
      solutions of low electrolyte concentrations aggregate at low pH values (pI
      approximately 3) and, unlike MS2, at large ionic strengths over the whole range
      of pH conditions considered in this study. These elements allow the determination
      of the hydrophobic sequence for the four phages SP approximately GA>Qbeta>MS2.
      Close inspection of the electrokinetic results reveals small to significant
      variations of the pI values-depending on the phage considered-with respect to the
      concentration of indifferent NaNO3 electrolyte. This indicates that features
      other than chemical and electrostatic in nature play a key role in determining
      the pI and more generally the electrophoretic mobility mu of viral particles. A
      qualitative interpretation is given and is based on the consideration of inner
      electro-osmotic flow within the isolated or aggregated particles. The impact of
      the flow properties within the particles is further in agreement with recent
      theoretical formalism developed for the electrokinetics of soft multiplayer
      particles, the phages analyzed here being some illustrative examples. The
      determination and qualitative interpretation of the surface properties of the
      viral particles as reported in the current study are commented within the context
      of water treatment especially concerning viral removal by membrane filtration
      processes.

PMID- 18329684
TI  - Productive infection of human immunodeficiency virus type 1 in dendritic cells
      requires fusion-mediated viral entry.
AB  - Human immunodeficiency virus type 1 (HIV-1) enters dendritic cells (DCs) through
      endocytosis and viral receptor-mediated fusion. Although endocytosis-mediated HIV
      1 entry can generate productive infection in certain cell types, including human
      monocyte-derived macrophages, productive HIV-1 infection in DCs appears to be
      dependent on fusion-mediated viral entry. It remains to be defined whether
      endocytosed HIV-1 in DCs can initiate productive infection. Using HIV-1 infection
      and cellular fractionation assays to measure productive viral infection and
      entry, here we show that HIV-1 enters monocyte-derived DCs predominately through
      endocytosis; however, endocytosed HIV-1 cannot initiate productive HIV-1
      infection in DCs. In contrast, productive HIV-1 infection in DCs requires fusion
      mediated viral entry. Together, these results provide functional evidence in
      understanding HIV-1 cis-infection of DCs, suggesting that different pathways of
      HIV-1 entry into DCs determine the outcome of viral infection.

PMID- 18329686
TI  - Evaluation of onsite sewage treatment and disposal systems in shallow karst
      terrain.
AB  - Two conventional onsite sewage treatment and disposal systems (OSTDSs) at Manatee
      Springs State Park, Florida, USA, were studied to assess their impact on
      groundwater quality in a shallow karst environment. Sulfur hexafluoride (SF6) and
      fluorescein were used as tracers to establish connections between the drainfields
      and monitoring wells. Elevated nutrients were found in all wells where
      significant concentrations of both tracers were observed, with the mean of the
      highest nitrate (NO3) concentration observed at each well being 47.8+/-14.9
      (n=11) mg/L NO3-N. The most elevated nutrient concentrations were found directly
      in the flow path of the effluent. Fecal coliform densities above 10 colony
      forming units (cfu)/100 mL were observed in wells with the most rapid connection
      to the drainfield. The proximity and connectivity of the 0.4-4m thick sandy
      surficial soils and the underlying karst aquifer allow rapid contaminant
      transport and limit the ability of conventional OSTDSs to attenuate NO3.

PMID- 18329687
TI  - Laboratory study highlights the key influences of stormwater sediment thickness
      and bioturbation by tubificid worms on dynamics of nutrients and pollutants in
      stormwater retention systems.
AB  - In urban area, the accumulation of polluted stormwater sediments (SWS) in
      retention ponds may be a source of dissolved pollutants and nutrients for the
      aquatic ecosystems. Our objective was to quantify the influence of the thickness
      of SWS layer and the occurrence of tubificid worms on organic matter processing
      (O(2) uptake and fluxes of NH(4)(+), NO(3)(-), PO(4)(3-), and dissolved organic
      carbon between sediment and water), releases of 17 PAHs and 4 heavy metals, and
      microbial characteristics. Results showed that oxidation of SWS organic matter
      (O(2) and NO(3)(-) uptakes) and releases of nutrients were significantly
      increased by the quantity of accumulated SWS and the worm bioturbation. Releases
      of acenaphtene and naphthalene from sediments were significantly increased by the
      thickness of the SWS layer. In contrast, tubificid worms did not promote the
      mobilization of pollutants. In conclusion, biological activities and stormwater
      sediment characteristics need to be assessed to quantify the fate of pollutants
      and nutrients in stormwater retention ponds.

PMID- 18329688
TI  - Degradation of organic pollutants in Mediterranean forest soils amended with
      sewage sludge.
AB  - The degradation of two groups of organic pollutants in three different
      Mediterranean forest soils amended with sewage sludge was studied for nine
      months. The sewage sludge produced by a domestic water treatment plant was
      applied to soils developed from limestone, marl and sandstone, showing
      contrasting alkalinity and texture. The compounds analysed were: linear
      alkylbenzene sulphonates (LAS) with a 10-13 carbon alkylic chain, and
      nonylphenolic compounds, including nonylphenol (NP) and nonylphenol ethoxylates
      with one and two ethoxy groups (NP1EO+NP2EO). These compounds were studied
      because they frequently exceed the limits proposed for sludge application to land
      in Europe. After nine months, LAS decomposition was 86-96%, and NP+NP1EO+NP2EO
      decomposition was 61-84%, which can be considered high. Temporal trends in LAS
      and NP+NP1EO+NP2EO decomposition were similar, and the concentrations of both
      types of compounds were highly correlated. The decomposition rates were higher in
      the period of 6-9 months (summer period) than in the period 0-6 months
      (winter+spring period) for total LAS and NP+NP1EO+NP2EO. Differences in decay
      rates with regard to soil type were not significant. The average values of decay
      rates found are similar to those observed in agricultural soils.

PMID- 18329689
TI  - Particle-facilitated lead and arsenic transport in abandoned mine sites soil
      influenced by simulated acid rain.
AB  - The role of acid rain in affecting Pb and As transport from mine tailings was
      investigated by pumping simulated acid rain at a infiltration rate of 10.2 cm/h
      through soil columns. Simulated acid rain with pH of 3.0, 4.5 and 5.6 were used
      as leaching solutions. Results showed that 86.9-95.9% of Pb and 90-91.8% of As
      eluted from the columns were adsorbed by particles in the leachates. Scanning
      electron microscopy (SEM) analysis showed that particles released from the
      columns were mainly composed of flocculated aggregates and plate or rod shaped
      discrete grains. Transmission electron microscopy (TEM) coupled with energy
      dispersive X-ray analysis (EDX) showed that these particles were predominantly
      silicate minerals. Results from our experiments demonstrated that when rapid
      infiltration conditions or a rainstorm exist, particle-facilitated transport of
      contaminants is likely to the dominant metal transport pathway influenced by acid
      rain.

PMID- 18329690
TI  - Detection of fungal development in closed spaces through the determination of
      specific chemical targets.
AB  - In addition to the biodegradation problems encountered in buildings, exposure of
      their occupants to moulds is responsible for numerous diseases: infections
      (invasive nosocomial aspergillosis), immediate or delayed allergies, food-borne
      infections and different types of irritation. In this context, the aim of our
      work has been to determine specific chemical tracers for fungal development on
      construction materials. More generally, by detecting a specific chemical
      fingerprint of fungal development, our objective was to propose a microbiological
      alert system which could control systems and/or procedures for the
      microbiological treatment of indoor areas. We therefore characterized the
      chemical emissions from six types of construction material contaminated
      artificially by moulds. Chemical fingerprints were established for 19 compounds
      arising specifically from fungal metabolism: 2-ethylhexanoic acid methyl ester, 1
      octen-3-ol, 3-heptanol, 3-methyl-1-butanol, 2-methyl-1-butanol, 1,3-octadiene, 2
      (5H)-furanone, 2-heptene, alpha-pinene, 2-methylisoborneol, 4-heptanone, 2
      methylfuran, 3-methylfuran, dimethyldisulfide, methoxybenzene, a terpenoid and
      three sesquiterpenes. Determining the origin of these compounds and their
      specific links with a growth substrate or fungal species made it possible to
      judge the pertinence of choosing these compounds as tracers. Thus the detecting
      specific volatile organic compounds emitted as from the second day of fungal
      growth demonstrated that this approach had the advantage of detecting fungal
      development both reliably and rapidly before any visible signs of contamination
      could be detected.

PMID- 18329691
TI  - Congenital visceral myopathy with a predominantly hypertrophic pattern treated by
      multivisceral transplantation.
AB  - Chronic intestinal pseudoobstruction due to visceral myopathy may cause
      intestinal failure. The anatomical pathology of visceral myopathy is dominated by
      an atrophic muscularis propria. We present a case that is overwhelmingly
      dominated by a hypertrophic muscularis propria. The hypertrophic pattern was
      documented from ages 2 to 28 years. Most descriptions of visceral myopathy focus
      on the atrophic pattern of injury to the muscularis propria, typified by vacuolar
      degeneration of myocytes, loss of muscle fibers, and frequently with a honeycomb
      pattern of fibrosis. Hypertrophic changes can be observed in visceral myopathy,
      but the hypertrophy typically represents only a minor feature, typically limited
      to the internal layer of the muscularis propria. In our patient, the observed
      muscular hypertrophy differed from most descriptions because it (a) was the
      dominant pattern of injury and (b) involved both layers of muscularis propria
      rather than just the inner circular layer. The patient had intestinal failure and
      the complications induced cirrhosis, eventually treated by multivisceral
      transplantation to correct the intestinal failure and cirrhosis.

PMID- 18329692
TI  - Histopathologic factors significantly associated with initial organ-specific
      metastasis by invasive ductal carcinoma of the breast: a prospective study.
AB  - The purpose of this study was to identify histologic factors significantly
      associated with initial organ-specific metastasis by 1044 invasive ductal
      carcinomas (IDCs) of the breast with and without adjuvant therapy, separately,
      according to nodal status and pathologic TNM stage status. The following
      histologic factors were prospectively analyzed by multivariate analyses for
      distant organ metastasis and bone metastasis in patients with IDC who did not
      receive adjuvant therapy, and for distant organ metastasis, bone metastasis,
      liver metastasis, and lung metastasis in patients with IDC who received adjuvant
      therapy: (1) invasive tumor size, (2) histologic grade, (3) tumor necrosis, (4)
      fibrotic focus (FF), (5) lymphatic invasion, (6) blood vessel invasion, (7)
      adipose tissue invasion, (8) skin invasion, (9) muscle invasion, (10) age, (11)
      estrogen (ER)/progesterone (PR) status, and (12) nodal status. The results showed
      that FF diameter greater than 8 mm and FF fibrosis grade 1 were the factors that
      most accurately predicted distant organ metastasis and bone metastasis in
      patients with IDC who did not receive adjuvant therapy. In patients with IDC who
      received adjuvant therapy, FF diameter greater than 8 mm was the factor that most
      accurately predicted bone metastasis, and the presence of tumor necrosis and ER
      /PR- were very important predictive factors for metastasis to the lung. Ten or
      more nodal metastases (N3) were the factor that most accurately predicted liver
      metastasis. Based on these findings, FF characteristics can be concluded to be
      the most important histologic factors for predicting metastasis to the bone, the
      presence of tumor necrosis and ER-/PR- for predicting metastasis to the lung, and
      N3 for predicting metastasis to the liver.

PMID- 18329693
TI  - Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue
      inhibitor of matrix proteinase 2 in prostate cancer: identification of patients
      with poor prognosis by immunohistochemistry.
AB  - Overexpression of the matrix metalloproteinase (MMP) 2 is associated with poor
      prognosis in many tumor types. Membrane-type-1 MMP (MMP14) activates MMP2 using
      pro-MMP2 specific inhibitor, tissue inhibitor of matrix proteinase 2 (TIMP2), as
      a receptor. We evaluated, by immunohistochemistry on 189 T3N0-2M0 prostate cancer
      (Pca) cases, the influence of MMP2, MMP14, and TIMP2 expression, individually and
      in association, on Pca disease-free survival (DFS). We evaluated marker
      expression separately in cancer, stromal, and benign epithelial (BE) cells
      according to a percentage scale (0%, <10%, 10%-50%, and >50%). Median follow-up
      was 4.61 years. In BE cells, there was an inverse relationship between initial
      prostate-specific antigen serum level and T3 stage with MMP14 expression (P =
      .003) and between pN stage and TIMP2 expression (P = .04). The most significant
      results with survival were obtained by dichotomizing the cases between those with
      less than 10% and at least 10% of cells expressing the marker, the latter
      category representing overexpression. TIMP2 overexpression in stromal cells was
      associated with a longer DFS with a hazard ratio of 0.573 (P = .02) for time to
      recurrence. MMP2 overexpression by BE cells correlated with a shorter DFS using a
      multivariate trend test (hazard ratio = 1.46, P = .02). Stromal cells expressing
      less than 10% TIMP2 and MMP2 overexpression was the only combination that was
      significantly associated with a shorter DFS (log-rank test, P = .0001). This
      study suggests that MMP14 is involved mostly in Pca implantation and that MMP2
      and TIMP2 expression by reactive stromal cells might be used as predictors of DFS
      in T3N0-2M0 Pca.

PMID- 18329694
TI  - Expression of matrix metalloproteinase 7 is an unfavorable postoperative
      prognostic factor in cholangiocarcinoma of the perihilar, hilar, and extrahepatic
      bile ducts.
AB  - Cholangiocarcinoma of the perihilar, hilar, and extrahepatic bile ducts
      (collectively referred to as the large bile ducts) is an intractable disease, and
      a papillary phenotype and well-differentiated histologic grade have been proposed
      as indicators of a favorable prognosis after surgical resection. In this study,
      we examined the significance of matrix metalloproteinases (MMPs) in
      cholangiocarcinoma with respect to clinicopathologic features. We subjected 66
      surgically resected specimens of cholangiocarcinoma of the large bile ducts to
      clinicopathologic examination, including postoperative survival, papillary
      phenotype, and immunohistochemical expression of MMP-2,-7, -9, and membrane type
      1 MMP (MT1-MP). Nonneoplastic biliary epithelium did not express these 4 MMPs,
      whereas cholangiocarcinoma frequently expressed MMP-2 (33.9%), -7 (75.8%), -9
      (47.5%), and MT1-MMP (54.5%). In particular, conventional (nonpapillary)
      cholangiocarcinoma expressed MMP-7 and MT1-MMP more frequently than papillary
      cholangiocarcinoma. The expression of MMP-7 and MT1-MMP significantly correlated
      with the nonpapillary phenotype, poorly differentiated histologic grade,
      perineural invasion, and advanced TNM stage. In contrast, the expression of MMP-2
      and -9 was not associated with any of the clinicopathologic features. Univariate
      analysis of disease-specific survival revealed that a papillary phenotype and
      expression of MMP-7 were prognostic factors of cholangiocarcinoma, in addition to
      TNM stage, poorly differentiated histologic grade, perineural invasion, and
      microscopic margin status. Multivariate analysis showed only TNM stage to be an
      independent prognostic factor. Expression of MMP-7 in cholangiocarcinoma is an
      unfavorable postoperative prognostic factor of cholangiocarcinoma arising from
      the large bile ducts. Underexpression of MMPs in papillary cholangiocarcinoma
      might be associated with a favorable prognosis.

PMID- 18329695
TI  - Midkine expression correlating with growth activity and tooth morphogenesis in
      odontogenic tumors.
AB  - Midkine (MK; a low molecular weight heparin-binding growth factor) is a
      multifunctional cytokine. MK plays a role in morphogenesis of many organs
      including teeth through epithelial-mesenchymal interactions. We
      immunohistochemically examined MK expression in various human odontogenic tumors.
      There was no difference in positive rate and intensity of MK between benign
      odontogenic tumors and their malignant counterparts. Ameloblastoma showed MK
      localization in the peripheral columnar cells in budding processes from the
      parenchyma, which frequently expressed proliferating cell nuclear antigen. MK was
      also preferentially expressed in keratinized cells in acanthomatous ameloblastoma
      and keratocystic odontogenic tumor. In odontogenic mixed tumors except for
      odontoma, intense immunoreactivity to MK was found in epithelial follicles, the
      surrounding odontogenic ectomesenchymal tissue, and the basement membrane between
      them. Intensity in the odontogenic ectomesenchyme decreased in relation to
      distance from the epithelial follicles. No expression was found in tumor cells
      associated with production of dental hard tissues in odontogenic mixed tumors
      including odontoma. These findings suggested that MK is involved in the
      reciprocal interaction between odontogenic epithelium and odontogenic
      ectomesenchymal tissue in areas without dental hard tissue formation in
      odontogenic mixed tumors. Coexpression of MK and proliferating cell nuclear
      antigen was also observed in epithelial follicles and highly cellular nodules in
      the ectomesenchyme of odontogenic mixed tumors. MK is considered to mediate
      growth activity of odontogenic tumors and cell differentiation of odontogenic
      mixed tumors through molecular mechanisms similar to those involved in
      morphogenesis of the tooth.

PMID- 18329696
TI  - Hypermethylation analysis of mismatch repair genes (hmlh1 and hmsh2) in locally
      advanced breast cancers in Indian women.
AB  - Alterations in protooncogenes and tumor-suppressor genes at the DNA and/or
      protein level, which indicate the biological properties of individual breast
      cancers, led us to design a study encompassing the dilemma of "epigenetic
      silencing-driven genomic instabilities." In this study, we analyzed the promoter
      methylation of potent mismatch repair genes (hmlh1 and hmsh2) for the first time
      in 232 Indian patients with primary breast cancer (using methylation-specific
      polymerase chain reaction and expressional analysis). The study evaluates the
      gamut of epigenetic aberrations as well as genomic instabilities (microsatellite
      instabilities and loss of heterozygosity) and includes analysis of BAT-25, BAT
      26, D2S123, D5S346, and D17S250. We observed hypermethylation of the hmlh1 gene
      in 43.5% of patients with primary breast cancer, of whom 66.9% had locally
      advanced breast cancer (stage IIIA, IIIB, and IIIC) (P < .0001). Similarly, we
      also found hypermethylation of the hmsh 2 gene in 16% of primary breast cancer
      cases. Of these patients, 21.3% had locally advanced breast cancer (P = . 01). To
      determine the effect of methylation, we also performed expressional studies using
      reverse transcriptase polymerase chain reaction and Northern blotting, but we
      were unable to get any significant expression in the presence of hypermethylation
      of either gene (hmlh1 and hmsh2). Interestingly, statistical analysis revealed
      that hypermethylation of the hmlh1 gene is one of the peculiar attributes of
      locally advanced breast cancer. In addition, this study indicates that for more
      sensitive stage-specific diagnosis or prognosis, both methylation of promoter and
      expression studies must be considered in the analyses in a reproducible manner.
      Therefore, pinpointing the methylation fingerprints (5'CpG island methylation) of
      potent DNA repairing genes not only shows the specific attributes of locally
      advanced breast cancer but also provides important insight into the mode of
      therapy to be used by clinical oncologists.

PMID- 18329697
TI  - Ground-level ozone prediction by support vector machine approach with a cost
      sensitive classification scheme.
AB  - For ground-level ozone (O(3)) prediction, a predictive model, with reliable
      performance not only on non-polluted days but, more importantly, on polluted
      days, is favored by public authorities to issue alerts, so that concerned
      citizens and industrial organizations could take precautions to avoid exposure
      and reduce harmful emissions. However, the class imbalance problem, i.e., in some
      collected field data, number of O(3) polluted days are much smaller than that of
      non-polluted days, will deteriorate the model performance on minority class-O(3)
      polluted days. Despite support vector machine (SVM) obtaining promising results
      in air quality prediction, in this study, a cost-sensitive classification scheme
      is proposed for the standard support vector classification model (S-SVC) in order
      to investigate whether the class imbalance plagues S-SVC. The S-SVC with such
      scheme is named as CS-SVC. Experiments on imbalanced data sets collected from two
      air quality monitoring sites in Hong Kong show that 1) S-SVC is still sensitive
      to class imbalance problem; 2) compared with S-SVC, CS-SVC effectively avoids
      class imbalance problem with lower percentage of false negative on O(3) polluted
      days but with higher percentage of false positive on non-polluted days; 3)
      compared with both S-SVC and CS-SVC, support vector regression model (SVR), after
      converting its output to binary one, only has similar performance with S-SVC,
      which indicates class imbalance problem also impairs the regressor model. From
      point of protecting public health, CS-SVC, which less likely misses to forecast
      O(3) polluted days, is recommended here.

PMID- 18329698
TI  - Impacts of biogenic emissions of VOC and NOx on tropospheric ozone during
      summertime in eastern China.
AB  - This study is intended to understand and quantify the impacts of biogenic
      emissions of volatile organic compounds (VOC) and nitrogen oxides (NO(x)) on the
      formation of tropospheric ozone during summertime in eastern China. The model
      system consists of the non-hydrostatic mesoscale meteorological model (MM5) and a
      tropospheric chemical and transport model (TCTM) with the updated carbon-bond
      chemical reaction mechanism (CBM-IV). The spatial resolution of the system domain
      is 30 km x 30 km. The impacts of biogenic emissions are investigated by
      performing simulations (36 h) with and without biogenic emissions, while
      anthropogenic emissions are constant. The results indicate that biogenic
      emissions have remarkable impacts on surface ozone in eastern China. In big
      cities and their surrounding areas, surface ozone formation tends to be VOC
      limited. The increase in ozone concentration by biogenic VOC is generally 5 ppbv
      or less, but could be more than 10 ppbv or even 30 ppbv in some local places. The
      impacts of biogenic NO(x) are different or even contrary in different regions,
      depending on the relative availability of NO(x) and VOC. The surface ozone
      concentrations reduced or increased by the biogenic NO(x) could be as much as 10
      ppbv or 20 ppbv, respectively. The impacts of biogenic emissions on ozone aloft
      are generally restricted to the boundary layer and generally more obvious during
      the daytime than during the nighttime. This study is useful for understanding the
      role of biogenic emissions and for planning strategies for surface ozone
      abatement in eastern China. Due to limitations of the emission inventories used
      and the highly non-linear nature of zone formation, however, some uncertainties
      remain in the results.

PMID- 18329699
TI  - Large-scale preparation of thrombin from human plasma.
AB  - Thrombin was prepared from human blood plasma (batch size 1200 L). First,
      prothrombin was isolated by the following separation techniques:
      cryoprecipitation, ion-exchange chromatography (diethyl aminoethyl, DEAE-IEX),
      heparin affinity chromatography, a second DEAE-IEX step, and immobilized metal
      affinity chromatography (IMAC). Prothrombin was then activated to thrombin, which
      was purified by hydrophobic interaction chromatography (HIC) and concentrated by
      ultrafiltration. This process is cost-effective because a waste fraction can be
      used from one of the steps (heparin affinity chromatography) in the commercial
      production of plasma-derived Factor IX (FIX). The final thrombin preparation had
      a purity of approximately 75% (specific activity approximately 2400 IU/mg
      protein), which is sufficient for its intended purpose in a fibrin glue. Sodium
      dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), Factor X (FX)
      activity analysis, and analytical HIC were also used to characterize the
      thrombin. Three substantially different techniques were used to reduce any viral
      activity, namely: solvent/detergent (S/D) treatment, pasteurization, and virus
      filtration (nanofiltration). The manufacturing process presented here would be
      suitable for large-scale production of thrombin with a high degree of virus
      safety.

PMID- 18329700
TI  - The effects of two highly selective dopamine D3 receptor antagonists (SB-277011A
      and NGB-2904) on food self-administration in a rodent model of obesity.
AB  - In the current study, we examined the effect of the selective D(3) receptor
      antagonists SB-277011A and NGB 2904 on operant food self-administration (FSA) in
      Zucker obese and lean rats. Obese (Ob) and lean (Le) Zucker rats were maintained
      under a restricted feeding regimen (70% of ad-libitum rat chow) and were trained
      to lever press for food during daily, 2 hour fixed-ratio 4 (FR4) schedules. Once
      rats reached a stable baseline for FSA, they were injected with vehicle until a
      stable FSA criterion was achieved. Animals then received daily injections of
      different random doses of SB-277011A (3, 10, and 30 mg/kg i.p.), and NGB-2904
      (0.3, 1 and 3 mg/kg i.p.). SB-277011A produced a significant decrease in both
      food intake and active lever responses in both Ob and Le rats. In contrast, NGB
      2904 did not decrease food intake levels or lever presses for food in Ob and Le
      rats. These results suggest that along with its involvement in seeking behavior
      for drugs of abuse, the D(3) dopamine receptor may also be involved in seeking
      behavior for natural reinforcers such as food.

PMID- 18329701
TI  - Effects of disulfiram and dopamine beta-hydroxylase knockout on cocaine-induced
      seizures.
AB  - The antialcoholism drug disulfiram has shown recent promise as a pharmacotherapy
      for treating cocaine dependence, probably via inhibition of dopamine beta
      hydroxylase (DBH), the enzyme that catalyzes the conversion of dopamine (DA) to
      norepinephrine (NE). We previously showed that DBH knockout (Dbh -/-) mice, which
      lack NE, are susceptible to seizures and are hypersensitive to the psychomotor,
      rewarding, and aversive effects of cocaine, suggesting that disulfiram might
      exacerbate cocaine-induced seizures (CIS) by inhibiting DBH. To test this, we
      examined CIS in wild-type and Dbh -/- mice following administration of disulfiram
      or the selective DBH inhibitor nepicastat. We found that Dbh genotype had no
      effect on CIS probability or frequency, whereas disulfiram, but not nepicastat,
      increased the probability of having CIS in both wild-type and Dbh -/- mice. Both
      disulfiram and nepicastat increased CIS frequency in wild-type but not Dbh -/-
      mice. There were no genotype or treatment effects on serum cocaine levels, except
      for an increase in disulfiram-treated Dbh -/- mice at the highest dose of
      cocaine. These results suggest that disulfiram enhances CIS via two distinct
      mechanisms: it both increases CIS frequency by inhibiting DBH and increases CIS
      frequency in a DBH-independent manner.

PMID- 18329702
TI  - Developmental lead exposure attenuates methamphetamine dose-effect self
      administration performance and progressive ratio responding in the male rat.
AB  - Perinatal (gestation/lactation) lead exposure modifies the reinforcement efficacy
      of various psychoactive drugs (e.g., cocaine, opiates) across the phases of
      initial selection, use, and abuse [Nation J.R., Cardon A.L., Heard H.M., Valles
      R., Bratton G.R. Perinatal lead exposure and relapse to drug-seeking behavior in
      the rat: a cocaine reinstatement study. Psychopharmacol 2003;168: 236-243.;
      Nation J.R., Smith K.R., Bratton G.R. Early developmental lead exposure increases
      sensitivity to cocaine in a self-administration paradigm. Pharmacol Biochem
      Behave 2004; 77: 127-13; Rocha A., Valles R., Cardon A.L., Bratton G.R., Nation
      J.R. Enhanced acquisition of cocaine self-administration in rats developmentally
      exposed to lead. Neuropsychopharmacol 2005; 30: 2058-2064.]. However, changes in
      sensitivity to methamphetamine across the phases of drug abuse have not been
      examined in animals perinatally exposed to lead. Because the mainstream
      popularity of methamphetamine in the United States is increasing and lead
      exposure continues to be widespread, an examination of this drug and how it may
      be modified by perinatal exposure to lead is warranted. The studies reported here
      examined the effects of perinatal lead exposure on adult self-administration of
      intravenous (i.v.) methamphetamine across the maintenance phase of drug
      addiction. Experiment 1 examined dose-effect patterns in control and lead-exposed
      animals. Experiment 2 evaluated control and lead-exposed animals in a progressive
      ratio task. Female rats were administered a 16-mg lead or a control solution for
      30 days prior to breeding with non-exposed males. Exposure continued through
      pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21).
      Animals born to control or lead-exposed dams received indwelling jugular
      catheters as adults (PND 70) and subsequently were randomly assigned to one of
      the two studies, using only one male rat per litter for each study. The data
      showed a general attenuation of the reinforcement efficacy of methamphetamine in
      animals perinatally exposed to lead, as compared to control animals.

PMID- 18329703
TI  - Linking Global Youth Tobacco Survey (GYTS) data to the WHO Framework Convention
      on Tobacco Control (FCTC): the case for the Seychelles.
AB  - Tobacco control has been recognized as a main public health concern in Seychelles
      for the past two decades. Tobacco advertising, sponsoring and promotion has been
      banned for years, tobacco products are submitted to high taxes, high-profile
      awareness programs are organized regularly, and several other control measures
      have been implemented. The Republic of Seychelles was the first country to ratify
      the WHO Framework Convention on Tobacco Control (FCTC) in the African region.
      Three population-based surveys have been conducted in adults in Seychelles and
      results showed a substantial decrease in the prevalence of smoking among adults
      between 1989 and 2004. A first survey in adolescents was conducted in Seychelles
      in 2002 (the Global Youth Tobacco Survey, GYTS) in a representative sample of
      1321 girls and boys aged 13-15 years. The results show that approximately half of
      students had tried smoking and a quarter of both boys and girls had smoked at
      least one cigarette during the past 30 days. Although "current smoking" is
      defined differently in adolescents (>or=1 cigarette during the past 30 days) and
      in adults (>or=1 cigarette per day), which precludes direct comparison, the high
      smoking prevalence in youth in Seychelles likely predicts an increasing
      prevalence of tobacco use in the next adult generation, particularly in women.
      GYTS 2002 also provides important data on a wide range of specific individual and
      societal factors influencing tobacco use. Hence, GYTS can be a powerful tool for
      monitoring the situation of tobacco use in adolescents, for highlighting the need
      for new policy and programs, and for evaluating the impact of current and future
      programs.

PMID- 18329704
TI  - Stress-reducing effects of indoor plants in the built healthcare environment: the
      mediating role of perceived attractiveness.
AB  - OBJECTIVE: Natural elements in the built healthcare environment have shown to
      hold potential stress-reducing properties. In order to shed light on the
      underlying mechanism of stress-reducing effects of nature, the present study
      investigates whether the stress-reducing effects of indoor plants occur because
      such an environment is perceived as being more attractive. METHOD: A single
      factor between-subjects experimental design (nature: indoor plants vs. no plants)
      was used in which participants (n=77) were presented with a scenario describing
      hospitalization with a possible legionella diagnosis. The study was conducted
      from March to May 2007 in the Netherlands. Subsequently, they were exposed to a
      photo of a hospital room. In this room were either indoor plants, or there was a
      painting of an urban environment on the wall. Afterwards, perceived stress and
      the perceived attractiveness of the hospital room were measured. RESULTS:
      Participants exposed to the hospital room with indoor plants reported less stress
      than those in the control condition. Mediation analysis confirmed that indoor
      plants in a hospital room reduce feelings of stress through the perceived
      attractiveness of the room. CONCLUSION: This study confirms the stress-reducing
      properties of natural elements in the built healthcare environment. It also sheds
      light on the underlying mechanism causing this stress-reduction.

PMID- 18329705
TI  - The effects of viscoelastic parameters on residual stress development in a
      zirconia/glass bilayer dental ceramic.
AB  - OBJECTIVES: The aim of this study was to test the hypothesis that the residual
      stresses in a zirconia-based bilayer dental composite system can be tailored
      through heat treatment above and below the glass transition temperature of glass
      veneers. METHODS: Ceramic bilayer disc specimens were prepared from a zirconia
      core and a glass veneer. Each bilayer ceramic group was heat treated 40 degrees C
      below, 20 degrees C and 40 degrees C above and at the glass transition
      temperature of the glass veneer, and cooled using a fast or a slow cooling rate.
      Specimens were tested for flexure strength using a biaxial bending fixture.
      Residual stresses were calculated using a fracture mechanics approach. RESULTS:
      Heat treatments produced significant differences (p < or =0.05) between the mean
      flexural strengths of the heat treatment groups when the specimens were cooled
      using a fast cooling rate. However, there was not a significant difference (p
      >0.05) between the mean flexural strengths of the heat treatment groups when a
      slow cooling rate was used. Fractures initiated from the veneer surfaces of the
      specimens. SIGNIFICANCE: Heat treatment above and below the glass transition
      temperature of the veneer layer, and the cooling rate have a significant effect
      on the flexural strength of the bilayer ceramic laminates. The existence of
      residual compressive stress is the most likely reason for the observed strength
      increases. Residual stresses can be modified using the elastic-viscoelastic
      relaxation behavior of a glass veneer.

PMID- 18329706
TI  - Fluorescent magnetic nanohybrids as multimodal imaging agents for human
      epithelial cancer detection.
AB  - Cetuximab conjugated fluorescent magnetic nanohybrids (CET-FMNHs) were
      synthesized for detection of human epithelial cancer via magnetic resonance (MR)
      and optical imaging. Spherical FMNHs consist of MnFe(2)O(4) magnetic nanocrystals
      encapsulated in pyrene-labeled PCL-b-PMAA as a surfactant prepared by a nano
      emulsion method. FMNHs demonstrated excellent colloidal stability and
      biocompatibility for biomedical application. Antibody conjugated fluorescent
      magnetic nanohybrids (CET-FMNHs) served as effective agents for both magnetic
      resonance (MR) and fluorescence optical imaging of cancer cell lines.

PMID- 18329707
TI  - Functionalized injectable hydrogels for controlled insulin delivery.
AB  - The concept of this research is using poly(beta-amino ester) (PAE) as a duo
      functional group for synthesis of the novel sensitive injectable hydrogel for
      controlled drug/protein delivery. Firstly, PAE made of 1,4-butanediol diacrylate
      and 4,4'-trimethylene dipiperidine is used as a pH-sensitive moiety to conjugate
      to the temperature-sensitive biodegradable triblock copolymer of poly(ethylene
      glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) to manufacture pH/temperature
      sensitive injectable hydrogel of pentablock copolymer PAE-PCL-PEG-PCL-PAE.
      Furthermore, the cationic nature of PAE is used as the second function to make
      the ionic complexes with anionic biomolecule loaded into the hydrogel such as
      insulin. As a result, the release of drug/protein from this hydrogel device can
      be controlled by the degradation of copolymer. Sol-gel phase transition behavior
      of PAE-PCL-PEG-PCL-PAE block copolymer was investigated; the results showed that
      the aqueous media of the pentablock copolymer changed from a sol to a gel phase
      with increasing temperature and pH. The effect of anionic biomolecule such as
      insulin on sol-gel phase transition, degradation of the complex gel of the
      material with insulin was studied in vitro. Then the schematic of the ionic
      complexes between positive charges in PAE and the negatively charges in protein
      was simulated. In addition, the mechanism of controlled release behavior of
      insulin from the complex gel was supposed, which includes the chemically
      controlled and diffusion-controlled stages. To prove the simulations, the
      cumulative release of the protein from the complex gel was investigated in vitro
      with different methods. Furthermore, the pharmacokinetic release of insulin from
      the complex gel in vivo on male Sprague-Dawley (SD) rats was compared with that
      from triblock copolymer hydrogel of PCL-PEG-PCL.

PMID- 18329708
TI  - The effect of poly(D,L-lactide-co-glycolide) microparticles with polyelectrolyte
      self-assembled multilayer surfaces on the cross-presentation of exogenous
      antigens.
AB  - A surface-engineered particulate delivery system for exogenous antigens was
      developed in this study. Poly(d,l-lactide-co-glycolide) (PLGA) microparticles
      containing ovalbumin (OVA) or fluorescein isothiocyanate-conjugated bovine serum
      albumin (FITC-BSA) were fabricated by the double emulsion and solvent evaporation
      method. Encapsulation of the PLGA microparticles was performed by physisorption
      of multilayers of oppositely charged polyelectrolytes, including polyethylenimine
      (PEI) and dextran sulfate. Surface charges of the particles after layer-by-layer
      (LbL) adsorption were determined by the zeta potential measurements. The uptake
      of these particles by the J774A.1 murine macrophages was examined by fluorescence
      microscopy. Generation of reactive oxygen species (ROS) in J774A.1 cells was
      determined by flow cytometry using 2',7'-dichlorodihydrofluorescein diacetate
      (DCFH-DA) and hydroethidine (HE). Antigen presentation assays were performed in
      B3Z cells, a hybridoma of OVA-specific CD8(+) T cells. Results obtained in this
      study demonstrated an effective ingestion of the PLGA microparticles and enhanced
      production of ROS in J774A.1 murine macrophages. Treatment of murine bone marrow
      derived dendritic cells (BMDCs) with polyelectrolyte-encapsulated PLGA
      microparticles resulted in an in vitro activation of B3Z cells, demonstrating the
      feasibility of induction of adaptive immunity for class I major
      histocompatibility complex (MHC) by surface engineering of microparticulate
      vaccine delivery.

PMID- 18329709
TI  - Trophoblast-derived heparanase is not required for invasion.
AB  - To invade the decidua and myometrium, extravillous trophoblast must degrade an
      assortment of extracellular matrix (ECM) components. The uterine wall is rich in
      heparan sulphate proteoglycans (HSPG), which interact with collagen, laminin and
      fibronectin, and bind a variety of growth factors. HSPG are catabolised by
      heparanase, an enzyme that is highly expressed in the placenta. The aim of this
      study was to investigate the role of heparanase in first trimester trophoblast
      invasion. First trimester cytotrophoblasts (CTB) were isolated by trypsin
      digestion followed by centrifugation on a Percoll gradient. Cells were cultured
      on Matrigel to promote an extravillous phenotype. Heparanase expression was
      studied by immunohistochemistry and confocal microscopy. Trophoblast invasion was
      assessed using an in vitro transwell assay. A high level of heparanase was
      observed in isolated first trimester trophoblast; however, a function-blocking
      antibody did not inhibit invasion of primary CTB or the extravillous trophoblast
      cell line SGHPL-4 at 21% oxygen. In contrast to cancer cells, heparanase
      expression was not increased following culture at 3% oxygen, and trophoblast
      invasion was not retarded by the blocking antibody under these conditions.
      Heparanase expression was observed in stromal cells and vascular endothelium in
      first trimester parietal decidua. Expression was evident on the cell surface and
      in the nucleus of trophoblast and decidual cells. In conclusion, trophoblast
      heparanase is not required for invasion in vitro. Its abundant expression
      suggests another role during pregnancy, perhaps in controlling the availability
      of ECM-bound growth factors or acting as a transcription factor.

PMID- 18329710
TI  - Microbial induction of B and T cell areas in rabbit appendix.
AB  - Gut-associated lymphoid tissue (GALT) development requires interaction with the
      intestinal microbiota. Because murine secondary lymphoid tissue development is
      driven by positive feedback interactions between B cells and stromal cells, we
      used in situ hybridization to determine whether intestinal commensals influence
      such interactions during rabbit appendix development. The features of positive
      feedback interactions we examined (CXCL13 mRNA expression, B cell accumulation
      and FDC differentiation) increased during early follicle development, but stalled
      in the absence of intestinal commensals. These features were reinitiated by
      commensals that stimulated follicle development and intrafollicular B cell
      proliferation. Our results suggest that rabbit appendix follicles develop in two
      phases: an initial phase of B cell recruitment to nascent follicles, possibly
      through positive feedback interactions, and a subsequent phase of intrafollicular
      B cell proliferation stimulated by intestinal commensals. In addition, we found
      that intestinal commensals stimulate appendix CCL21 mRNA expression and T cell
      area formation.

PMID- 18329711
TI  - Altered energetics and parasitism in juvenile northern pike (Esox lucius)
      inhabiting metal-mining contaminated lakes.
AB  - The objective of this study was to evaluate possible factors that could be
      contributing to altered bioenergetics of juvenile northern pike (Esox lucius)
      living in lakes receiving effluent from the Key Lake uranium mill in northern
      Saskatchewan, Canada. Although glycogen and triglycerides stores in liver and
      muscle were significantly greater in pike from exposure lakes compared to the
      reference, triglycerides stores of aquatic insects and spottail shiners that are
      prey items of juvenile pike showed no overall differences among lakes. Measures
      of parasitism, on the other hand, were negatively correlated with pike
      bioenergetics thereby reflecting a possible energetic cost of parasitism on
      reference lake fishes. The degree of infection, as measured by the abundance and
      biomass of intestinal parasites and the abundance of monogeneans on pike gills,
      was greatest in reference fishes and intermediate in low-exposure pike, whereas
      high-exposure fishes harbored no parasites.

PMID- 18329712
TI  - Antimicrobial drug resistance as determined by the E-test in Campylobacter
      jejuni, C. coli, and C. lari isolates from the ceca of broiler and layer chickens
      in Grenada.
AB  - One hundred and twenty five chickens from Grenada, consisting of 77 broilers and
      48 layers were examined for carriage of thermophilic campylobacters in their ceca
      by culture. Seventy nine percent of chickens were positive for campylobacters,
      with an isolation rate of 93.5% for broilers and 56.3% for layers, the difference
      being significant. Sixty-four pure cultures comprising 39 Campylobacter coli, 21
      Campylobacter jejuni, and 4 Campyilobacter lari isolates were tested for their
      resistance against 7 antibiotics using the E-test. None of the isolates were
      resistant to chloramphenicol and gentamicin. Resistance rates to other drugs
      were: ampicillin, 9.4%; ciprofloxacin, 12.5%; erythromycin, 3.1%; metronidazole,
      9.4%, and tetracycline, 50% with MICs of >or=256 microg/mL for tetracycline.
      There were no significant differences in resistance rates between C. coli and C.
      jejuni. Multiple resistance to >or=2 drugs was seen in 15.6% of total isolates.
      All C. lari isolates were resistant to ciprofloxacin, and 3 of 4 isolates had
      multiple drug resistance. Overall, erythromycin, which is the drug of choice for
      treatment of Campylobacter infections in humans, is effective in vitro against
      97% of chicken isolates in Grenada.

PMID- 18329713
TI  - Neuro-imaging of cerebral ischemic stroke.
AB  - Major progress has recently been made in the neuro-imaging of stroke as a result
      of improvements in imaging hardware and software. Imaging may be based on either
      magnetic resonance imaging (MRI) or computed tomography (CT) techniques. Imaging
      should provide information on the entire vascular cervical and intracranial
      network, from the aortic arch to the circle of Willis. Equally, it should also
      give information on the viability of brain tissue and brain hemodynamics. CT has
      the advantage in the detection of acute hemorrhage whereas MRI offers more
      accurate pathophysiological information in the follow-up of patients.

PMID- 18329714
TI  - Social information processing, subtypes of violence, and a progressive
      construction of culpability and punishment in juvenile justice.
AB  - Consistent with core principles of liberal theories of punishment (including
      humane treatment of offenders, respecting offender rights, parsimony, penal
      proportionality, and rehabilitation), progressive frameworks have sought to
      expand doctrines of mitigation and excuse in order to reduce culpability and
      punishment. With respect to juvenile justice, scholars have proposed that
      doctrinal mitigation be broadened, and that adolescents, due to aspects of
      developmental immaturity (such as decision-making capacity), be punished less
      severely than adults who commit the same crimes. One model of adolescent
      antisocial behavior that may be useful to a progressive theory of punishment in
      juvenile justice distinguishes between instrumental violence, by which the actor
      behaves thoughtfully and calmly to achieve personal gain, and reactive violence,
      which is characterized as impulsive, emotional retaliation toward a perceived
      threat or injustice. In particular, social cognitive differences between
      instrumental and reactive violence have implications for responsibility, length
      and structure of incarceration, rehabilitation, and other issues that are central
      to a progressive theory of juvenile culpability and punishment.

PMID- 18329715
TI  - Mental health policy in the liberal state: the example of the United States.
AB  - Mental health policy arises out of the interaction of many different variables.
      These include (but are not limited to) the composition of the population of
      persons with severe mental illnesses; the means of dealing with disease and
      dependency; concepts of the etiology and nature of mental disorders; the
      organization and ideology of psychiatry; funding mechanisms; and existing
      popular, political, cultural, and professional values. But an often neglected but
      crucial factor in shaping policy is the very structure of the American political
      system, which played a crucial role in shaping mental health policy. Rather than
      emphasizing the neo-liberal theory and its accompanying hostility toward
      "unsuccessful" people and disdain of welfare, this article suggests that an
      understanding of mental health policy in the latter half of the twentieth century
      is better served by an examination of what actually happened. Theory, however
      attractive, rarely can encompass the messy data of reality.

PMID- 18329716
TI  - Ototoxicity induced by cinnabar (a naturally occurring HgS) in mice through
      oxidative stress and down-regulated Na(+)/K(+)-ATPase activities.
AB  - Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in
      Chinese mineral medicine for more than 2000 years; currently it is still used as
      a sedative for infants in Asian countries. Since methylmercury is potently
      ototoxic, whether cinnabar also induces hearing impairment is awaited for
      delineation. In this study, we attempted to explore the toxic effects of cinnabar
      on the auditory brainstem response (ABR) system during 2-10 weeks administration
      at a clinical oral dosage of 10mg/kg/day in mice. The results showed that Hg
      contents of the brainstem were significantly increased accompanied with gradually
      progressive abnormality of ABR during 4-10 weeks of cinnabar administration. The
      progressive increase in hearing thresholds, prolonged absolute and interwave
      latencies of ABR apparently exhibited a gender difference. Male mice were more
      sensitive to cinnabar in producing hearing impairment correlated with the
      biochemical alterations in plasma and brainstem, e.g. an increase of lipid
      peroxidation (LPO), altered Na(+)/K(+)-ATPase activities and decrease of nitric
      oxide (NO(x)) levels. Moreover, accumulation of Hg contents in brainstem with a
      greater extent was found in male mice. These findings provide important
      information that the clinical dosage of cinnabar (10mg/kg/day) still exhibited
      ototoxicity after continuously long-term exposure. The signaling pathway of
      oxidative stress/Na(+)-K(+)-ATPase activities/NO of brainstem (a central auditory
      regulatory system) probably plays an important role in the toxic mechanisms of
      cinnabar-induced ototoxicity. The gender difference in cinnabar-induced
      neurotoxic effects merits further investigation.

PMID- 18329717
TI  - Syntheses and characterization of copper complexes with the ligand 2-aminoethyl(2
      pyridylmethyl)-1,2-ethanediamine (apme).
AB  - Copper(I)/(II) complexes with the ligand 2-aminoethyl(2-pyridylmethyl)1,2
      ethanediamine (apme, abbreviated as PDT in the literature as well) were prepared
      and characterized. Crystal structures of the copper(I) complexes, [Cu2(apme)2]X2
      (1, 2; X=ClO4, CF3SO3), showed that they are dinuclear, in contrast to the
      trigonal bipyramidal copper(II) complexes [Cu(apme)Cl]BPh4 (3) and
      [Cu(apme)(DMF)](BPh4)2 (4). 1 and 2 could be investigated in solution by NMR
      spectroscopy and 3 and 4 by cyclovoltammetry. From the results of these studies
      it is clear that in solution equilibria between the dinuclear complexes 1/2 and
      another species exist, most likely the monomeric [Cu(apme)CH3CN]+. Time-resolved
      UV/vis spectra at low temperatures allowed the spectroscopic detection of
      dioxygen adduct complexes as reactive intermediates during the oxidation of 1/2
      with dioxygen that seem to play an important role in copper enzymes such as
      peptidylglycine-alpha-hydroxylating monooxygenase (PHM).

PMID- 18329718
TI  - A case of Dirofilaria pulmonary infection coexisting with lung cancer.
AB  - Dirofilaria immitis, the dog heartworm, may accidentally infect humans and
      manifest as a subpleural solitary or multiple pulmonary nodules that are often
      difficult to differentiate from primary or metastatic lung tumors. Our patient
      had biopsy proven lung cancer and a second lesion found to be pulmonary
      dirofilariasis after excision. The coexistence of pulmonary infection and cancer
      must be considered whenever 2 or more lesions have different clinical and
      radiologic behavior. Pulmonary dirofilariasis is a rare cause of lung nodules and
      may be present with lung cancer even more infrequently.

PMID- 18329719
TI  - Development of potentiometric urea biosensor based on urease immobilized in PVA
      PAA composite matrix for estimation of blood urea nitrogen (BUN).
AB  - A urea biosensor was developed using the urease entrapped in polyvinyl alcohol
      (PVA) and polyacrylamide (PAA) composite polymer membrane. The membrane was
      prepared on the cheesecloth support by gamma-irradiation induced free radical
      polymerization. The performance of the biosensor was monitored using a flow
      through cell, where the membrane was kept in conjugation with the ammonia
      selective electrode and urea was added as substrate in phosphate buffer medium.
      The ammonia produced as a result of enzymatic reaction was monitored
      potentiometrically. The potential of the system was amplified using an electronic
      circuit incorporating operational amplifiers. Automated data acquisition was
      carried by connecting the output to a 12-bit analog to digital converter card.
      The sensor working range was 1-1000 mM urea with a response time of 120 s. The
      enzyme membranes could be reused 8 times with more than 90% accuracy. The
      biosensor was tested for blood urea nitrogen (BUN) estimation in clinical serum
      samples. The biosensor showed good correlation with commercial Infinitytrade mark
      BUN reagent method using a clinical chemistry autoanalyzer. The membranes could
      be preserved in phosphate buffer containing dithiothreitol, beta-mercaptoethanol
      and glycerol for a period of two months without significant loss of enzyme
      activity.

PMID- 18329720
TI  - Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar
      Disorder: a 4-year follow-up naturalistic study.
AB  - BACKGROUND: The aim of this naturalistic study was to compare the effectiveness
      of quetiapine and classical mood stabilizers, as mono- or combination therapy, in
      the long-term treatment of Bipolar Disorder (BD). METHODS: 232 DSM-IV BD I (n=91)
      or BD II (n=141) patients, treated and followed up for four years, were studied.
      Mood stabilizers were chosen by the treating psychiatrists on the basis of their
      clinical judgement. The sample was subdivided into 6 treatment groups: quetiapine
      (n=41), lithium (n=39), sodium valproate (n=73), lamotrigine (n=31), quetiapine
      plus lithium (n=25), and quetiapine plus sodium valproate (n=23). Throughout the
      4-year follow-up period patients were assessed monthly, or whenever a recurrence
      occurred, by the administration of HAMD-21 and of the YMRS. Primary outcome
      measures were the duration of euthymia and the cumulative proportion of subjects
      who maintained euthymia. Kaplan-Meier survival analyses were done to tabulate and
      compare the differences in survival distributions across the different treatment
      groups (Log-Rank Mantel-Cox test). RESULTS: The combined treatments with
      quetiapine plus lithium or sodium valproate were more effective overall in
      maintaining euthymia, (percentages of patients who maintained euthymia: 29.3% for
      quetiapine, 46.2% for lithium, 32.9% for sodium valproate, 41.9% lamotrigine, 80%
      for quetiapine plus lithium, and 78.3% for quetiapine plus sodium valproate). In
      addition, quetiapine monotherapy was as effective as lithium monotherapy or
      combination treatment with lithium or sodium valproate in preventing the
      recurrence of major depressive episodes. LIMITATION: The main limitations of the
      study are the lack of randomized, controlled conditions and the low doses of
      quetiapine used. CONCLUSION: If the results from this study will be replicated,
      there will be important implications for the use of quetiapine in the long-term
      treatment of BD.

PMID- 18329721
TI  - Clinical factors influencing the prescription of antidepressants and
      benzodiazepines: results from the European study of the epidemiology of mental
      disorders (ESEMeD).
AB  - OBJECTIVE: To examine factors associated with the use of antidepressants (AD) and
      benzodiazepines (BZD) in 6 European countries. METHODS: A cross-sectional,
      population-based study was conducted in: Belgium, France, Germany, Italy, the
      Netherlands and Spain. 21,425 non-institutionalized individuals aged 18 years and
      over were interviewed using the third version of the Composite International
      Interview (CIDI-3.0). Respondents were asked about AD and BZD use, and whether
      they consulted formal health services for emotional problems in the previous
      year. Sociodemographic variables, presence of mood/anxiety disorders and of
      painful physical symptoms were collected. RESULTS: 34.38% and 9.17% of the sample
      reported the use of AD and BZD respectively in the previous 12 months. Only
      29.95% of subjects with a 12-month prevalence of major depressive episode (MDE)
      had been taking antidepressants. After controlling for several clinical and non
      clinical factors, help seeking for emotional problems was the most important
      independent predictor for the use of AD or BZD (OR: 13.58 and 5.17,
      respectively). Higher age was the second important predictor (OR: 6.52 and 4.86,
      respectively). A 12-month or lifetime prevalence of MDE or an anxiety disorder
      were also predictors for AD or BZD use (OR for MDE: 5.00 and 2.82, OR for anxiety
      disorders: 2.13 and 1.85). Finally, the presence of painful physical symptoms
      also predicted the use of AD and BZD, while female gender, lower education and
      higher age predicted only the use of BZD. CONCLUSION: Less than one third of
      subjects with a 12-month prevalence of MDE had been taking antidepressants. But
      seeking help for emotional problems was a more important predictor of the use of
      ADs or BZDs than a formal (DSM-IV) psychiatric diagnosis, suggesting that usage
      of ADs is not always according to the licensed DSM-IV indication.

PMID- 18329722
TI  - Content and style of speech from mothers with schizophrenia towards their
      infants.
AB  - Schizophrenia can affect verbal communication and relational processes, but how
      it might disrupt maternal infant-directed (ID) speech is unknown. Maternal speech
      characteristics were coded, blind to clinical information, from brief videotaped
      mother-infant interactions of 14 mothers with schizophrenia and 36 mothers with
      similar hospitalisation but with other clinical diagnoses. Compared with the non
      schizophrenia group, the speech of mothers with schizophrenia was less infant
      focused. Infant-focused content was also predicted by maternal age, but not by
      duration of hospitalisation or infant gender. Mothers with schizophrenia also
      used significantly fewer songs or rhymes than the comparison group, and showed a
      trend towards fewer negative comments. Speech prosody/content deviations were
      rarely observed in either group, and no differences were found in speech rate or
      structure. The marked lack of ID speech content of mothers with schizophrenia
      reflects low maternal sensitivity, perhaps due to 'theory of mind' impairment and
      blunted affect, and may contribute to the early developmental vulnerability of
      their children.

PMID- 18329723
TI  - Effects of sad mood on facial emotion recognition in Chinese people.
AB  - This study examined the influence of sad mood on the judgment of ambiguous facial
      emotion expressions among 47 healthy volunteers who had been induced to feel sad
      (n=13), neutral (n=15), or happy (n=19) emotions by watching video clips. The
      findings suggest that when the targets were ambiguous, participants who were in a
      sad mood tended to classify them in the negative emotional categories rather than
      the positive emotional categories. Also, this observation indicates that emotion
      specific negative bias in the judgment of facial expressions is associated with a
      sad mood. The finding argues against a general impairment in decoding facial
      expressions. Furthermore, the observed mood-congruent negative bias was best
      predicted by spatial perception. The findings of this study provide insights into
      the cognitive processes underlying the interpersonal difficulties experienced by
      people in a sad mood, which may be predisposing factors in the development of
      clinical depression.

PMID- 18329724
TI  - Attention deficit in depressed suicide attempters.
AB  - Attention is typically impaired in depression and may play a role in risk for
      suicidal behavior. In this study, 66 non-patients, 83 depressed subjects with no
      past history of suicide attempt, 53 depressed subjects with one or more low
      lethality suicide attempts, and 42 depressed subjects with at least one high
      lethality attempt were compared on two computerized measures of attention, a
      continuous performance test (CPT) and a Stroop task. All subjects were medication
      free at the time of assessment. Attention was impaired in all depressed subjects
      but worse in those with a past history of suicidal behavior. CPT performance did
      not differ among the groups, but Stroop interference was significantly poorer in
      all depressed subjects relative to non-patients, and poorer still in high
      lethality suicide attempters relative to all other groups. Interference scores
      correlated modestly with subjective depression, functional level, suicide
      ideation, number of past suicide attempts, and lethality of past attempts.
      Depression-related impairments of attention, especially susceptibility to
      interference, are accentuated in those with a past history of suicidal behavior.
      Fundamental deficits in attentional control may play a role in risk for suicidal
      behavior, and may contribute to a variety of cognitive deficits in suicidal
      patients. Brain regions subserving attentional control, which overlap
      considerably with regions implicated in affective disorders, may be a useful
      target for studies seeking to characterize neuropsychological factors associated
      with suicidal behavior.

PMID- 18329725
TI  - Increased level of IL-32 during human immunodeficiency virus infection suppresses
      HIV replication.
AB  - Interleukin-32 was recently identified as a pro-inflammatory cytokine produced by
      T-lymphocytes, natural killer cells, epithelial cells, and blood monocytes. IL-32
      is induced by IFN-gamma in a time-dependent manner suggesting a role for IL-32 in
      innate and adaptive immune responses. In this study we present evidence that
      Human immunodeficiency virus promotes interleukin-32 production at both mRNA and
      protein levels. Our results showed that there is a 74% increase in the serum
      levels of IL-32 among HIV patients as compared to healthy individuals. There was
      a three-fold increase in the promoter activity of the IL-32 in the present
      infections HIV clone. This increase in IL-32 promoter activity was substantiated
      by increased IL-32 mRNA and protein levels. We have also demonstrated that IL-32
      suppresses HIV replication. Our results show that HIV LTR activity was increased
      by more than six-folds when endogenous IL-32 was knocked down by IL-32-specific
      siRNA whereas it decreased by one-fold when IL-32 was over expressed in the
      cells. Similarly a more than two-fold increase and a 50% decrease in HIV p24
      values were noted when IL-32 was knocked down and when IL-32 was over expressed
      in the cells, respectively. Our present work shows that raised IL-32 levels in
      HIV infection may in turn hamper HIV replication; one of the protective
      mechanisms of nature.

PMID- 18329726
TI  - Low and dysregulated BDNF secretion from immune cells of MS patients is related
      to reduced neuroprotection.
AB  - Multiple sclerosis (MS) is characterized by lesions with inflammatory
      infiltration, demyelination and axonal damage in the CNS white matter that
      correlates with the extent of disease disability. Knowledge of up-regulatory
      triggers of neuroprotective pathways in the CNS is essential for the development
      of the next generation of disease therapies. Recent studies have suggested a
      neuroprotective activity of the lesion-infiltrating immune cells. We studied the
      secretion of brain-derived neurotrophic factor (BDNF) from the immune cells of
      untreated patients with relapsing remitting (RR) MS with mild to moderate
      disability and sought immune factors that regulate the BDNF levels and affect the
      survival of neuronal cells in vitro. We found lower than normal secreted levels
      of BDNF from the immune cells of these patients. The normal effect of CD40
      stimulation that up-regulates BDNF secretion levels and induces neuroprotection
      was absent in the MS patients, while the expression of CD40 on their monocytes
      was elevated. The failure of BDNF availability from immune cells in patients with
      RR-MS and the loss of a neuroprotective effect by these cells may be related to a
      more widespread phenomenon of deviated immunity in MS, and may be linked to the
      continuous CNS neuronal tissue loss during the course of this disease.

PMID- 18329728
TI  - Association between nasal polyposis, Dubowitz syndrome and hyper-IgE syndrome.
AB  - Dubowitz syndrome is a rare, autosomal recessive disorder characterized by
      intrauterine growth retardation, short stature, microcephaly, distinct facial
      dysmorphism, and psychomotoric retardation. The hyper-immunoglobulin E (hyper-IgE
      or Job syndrome) is a primary immunodeficiency characterized by recurrent
      staphylococcal abscesses, recurrent cyst-forming pneumonia, and an elevated serum
      IgE level of >2000 IU/ml. We present the first case to our knowledge of an
      association between Dubowitz syndrome, hyper-IgE syndrome, and nasal polyposis
      (due to allergic fungal sinusitis) in a 14-year-old girl. Eosinophilic
      inflammatory reaction is the feature present in all three conditions. Unlike most
      cases of allergic fungal sinusitis, this case was not treated with an initial
      booster of oral steroids due to the risk of disseminated invasive fungal
      infection, reported in other cases of hyper-IgE syndrome. The case and its
      management is presented and discussed.

PMID- 18329727
TI  - Chronic CXCL10 alters the level of activated ERK1/2 and transcriptional factors
      CREB and NF-kappaB in hippocampal neuronal cell culture.
AB  - Signal transduction pathways may be important targets of chemokines during
      neuroinflammation. In the current study, Western blot analyses show that in rat
      hippocampal neuronal/glial cell cultures chronic CXCL10 increases the level of
      protein for ERK1/2 as well as for the transcriptional factors CREB and NF-kappaB.
      Bcl-2, an anti-apoptotic protein whose expression can be regulated by a pathway
      involving ERK1/2, CREB and NF-kappaB, was also increased in the CXCL10 treated
      cultures. These results implicate a role for ERK1/2, CREB and NF-kappaB in
      effects of CXCL10 on hippocampal cells and suggest that chronic CXCL10 may have a
      protective role during certain neuroinflammatory conditions.

PMID- 18329729
TI  - Detection of canine adenoviral infections in urine and faeces by the polymerase
      chain reaction.
AB  - The present study was aimed at developing the polymerase chain reaction (PCR)
      assay for detection of canine adenoviruses from faecal or urine samples. Urine or
      faecal samples were treated with chloroform or activated charcoal to eliminate
      the PCR inhibitory substances and the total DNA was extracted. The PCR was
      optimized using common set of primers to amplify 508 bp or 1,030 bp DNA sequence
      within E3 gene of canine adenovirus-1 (CAV-1) and canine adenovirus-2 (CAV-2),
      respectively. The PCR assay could detect up to 0.016 TCID(50) viruses from CAV-1
      infected MDCK cell culture fluid, 1.6 TCID(50) viruses from faeces and 16
      TCID(50) viruses from urine. In addition, the PCR assay was validated using
      clinical samples. Based on the results, it is concluded that, the present PCR
      assay can be used for rapid detection of canine adenoviral infections.

PMID- 18329730
TI  - Detection of human herpesviruses HHV-6, HHV-7 and HHV-8 in whole blood by real
      time PCR using the new CMV, HHV-6, 7, 8 R-gene kit.
AB  - Human herpesviruses 6 (HHV-6), 7 (HHV-7) and 8 (HHV-8) are lymphotropic
      herpesviruses that may cause opportunistic diseases in immunosuppressed patients
      such as transplant or AIDS patients. The new commercial CMV HHV-6, 7, 8 R-gene
      kit (Argene, Varilhes, France) for the simultaneous quantitation of HHV-6 and
      qualitative detection of HHV-7 and HHV-8 was evaluated using whole blood samples
      (respectively, n=175, 100 and 161) and using different extraction and real-time
      PCR platforms in two Centers A and B. In comparison with HHV-6 in-house real-time
      PCR the commercial kit showed agreements of 96% (n=75) and 85% (n=100) in A and
      B, respectively, with significant Spearman's correlation between both techniques
      (in A: r=0.97 [p<0.001]; in B: r=0.70 [p<0.001]). The Bland-Altman test results
      and prospective monitoring of patients confirmed the accuracy of these HHV-6 real
      time PCR techniques. The agreement between the in-house HHV-7 PCR and commercial
      kit was of 86% (n=100). In comparison with in-house HHV-8 real-time PCRs, the
      commercial kit showed agreements of 100% (n=61) and 93.7% (n=96) in A and B,
      respectively. These results demonstrate that the new commercial CMV HHV-6, 7, 8 R
      gene kit was an efficient and reliable tool for the diagnosis of herpesvirus 6,
      7, 8 infections.

PMID- 18329731
TI  - Comparison of low-density arrays, RT-PCR and real-time TaqMan RT-PCR in detection
      of grapevine viruses.
AB  - Low-density arrays (LDA) have been designed based on the real-time RT-PCR
      (TaqMan) assays for the specific detection of 13 viruses that infect Grapevines
      in addition to the housekeeping gene 18S rRNA. The viruses included in the study
      are Grapevine leafroll associated viruses 1, 2, 3, 4, 5, and 9, Grapevine
      leafroll associated virus-2 Redglobe (GLRaV-2RG) strain, Ruspestris stem pitting
      associated virus, Grapevine vitivirus A, Grapevine vitivirus B, Grapevine fanleaf
      virus, Tomato ringspot virus (ToRSV), and Grapevine fleck virus (GFkV). This
      study includes three new TaqMan RT-PCR assays that have been developed for GLRaV
      2RG, GFkV and ToRSV and have been included in the TaqMan RT-PCR and LDA
      detection. The LDAs were evaluated against a wide range of isolates distributed
      geographically. Geographical locations included Africa, Europe, Australia, Asia,
      Latin America and the United States. High-throughput detection of these viruses
      using LDAs was compared to RT-PCR and real-time TaqMan RT-PCR. The efficiency of
      different RNA extraction methodologies and buffers were compared for use in low
      density array detection. In addition improving the RNA extraction technique and
      testing the quality of the RNA using the 18S ribosomal RNA TaqMan assay as an RNA
      specific internal control proved to generate better diagnostic assays. This is
      the first report on the use of LDA for the detection of plant viruses.

PMID- 18329732
TI  - Characterization of the genome of human enteroviruses: design of generic primers
      for amplification and sequencing of different regions of the viral genome.
AB  - Human enteroviruses are among the most common viruses infecting humans and can
      cause diverse clinical syndromes ranging from minor febrile illness to severe and
      potentially fatal diseases. Biodiversity and evolution of human enterovirus
      genomes are shaped by frequent recombination events. Therefore, identification
      and characterization of circulating strains of enteroviruses require partial
      determination of different genomic regions. The development is described of a
      simple method allowing amplification and partial sequencing of the P1, P2 and P3
      genomic regions of field human enterovirus strains isolated in cell cultures, by
      performing PCR on cDNAs generated through a single RT reaction. A set of generic
      primers were designed and tested on a panel of 90 field and prototype viruses
      belonging to the five species of human enteroviruses. This assay was shown to
      amplify efficiently the targeted regions of all the 90 genomes tested. The
      generated amplicons were sequenced successfully without the need for gel
      purification. This assay could be a valuable tool for laboratories interested in
      molecular epidemiology and evolution studies implicating a great number of human
      enterovirus strains isolated from human or environmental samples.

PMID- 18329733
TI  - Defining memories by their distinct molecular traces.
AB  - It is often stated that short-term memory is consolidated in a protein-synthesis
      dependent manner into long-term memory. Alternatively, memories might consist of
      distinct molecular traces that last for different periods of time. These traces
      can be graded by their 'volatility'; traces encoded by activation of protein
      kinases are more volatile than traces encoded by morphological changes at
      preexisting synapses. The least volatile ('static') traces are due to the
      generation and stabilization of new synapses. Importantly, whereas at the
      cellular level these traces are generated independently of each other, they might
      be linked at the network level where volatile memory traces are required to set
      up a cellular network that is in turn required to induce the static memory trace.

PMID- 18329734
TI  - Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor
      neurons within the brain and spinal cord are lost, leading to paralysis and
      death. Certain growth factors should, in principle, be able to protect dying
      motor neurons. However, targeted delivery to the spinal cord or brain has been a
      constant problem. There is also accumulating evidence that glial cells might play
      a crucial role in maintaining motor neuron function and survival in ALS. Stem
      cells isolated and expanded in culture can be modified to release growth factors
      and generate glial cells following transplantation into the spinal cord or brain.
      As such, they might be able to both detoxify the local environment around dying
      motor neurons and deliver trophic factors. Here we examine the feasibility of
      translating these findings into new treatments for ALS patients.

PMID- 18329735
TI  - Stress, sensitive periods and maturational events in adolescent depression.
AB  - In this paper, we provide an overview of how the maturation of specific brain
      regions and stress exposure during windows of vulnerability initiate a series of
      events that render adolescents exceptionally susceptible to the development of
      depression. This stress-incubation/corticolimbic development cascade provides a
      means of understanding why depression emerges with such force and frequency in
      adolescence. The development of the prefrontal cortex, hippocampus, amygdala and
      ventral striatum is described from a translational perspective as they relate to
      stress exposure, onset, pathogenesis and gender differences in depression.
      Adolescent depression is a serious recurrent brain-based disorder. Understanding
      the genesis and neurobiological basis is important in the development of more
      effective intervention strategies to treat or prevent the disorder.

PMID- 18329736
TI  - Toll-like receptors: roles in neuroprotection?
AB  - Toll-like receptors (TLRs) enable mammalian cells to sense pathogenic challenges.
      They are essential for appropriate initiation, execution and regulation of innate
      and adaptive immune responses. Whereas TLR-mediated processes in the central
      nervous system (CNS) might contribute to detrimental (auto)immune reactions, they
      are unlikely to have exclusively neurodestructive consequences. Indeed,
      appropriately controlled TLR signaling might be crucial for preserving CNS
      structure and function in certain contexts. Recent findings illustrate
      neuroprotective capacities for TLRs, mediated by containment of trauma-associated
      infection or by recruitment of neuroprotective T lymphocytes. By the latter
      mechanism, endogenous or therapeutically administered TLR ligands could
      conceivably generate neuroprotective benefits in noninfectious CNS disorders.
      This article focuses on the yet less-addressed protective potential of TLR
      engagement within the CNS.

PMID- 18329737
TI  - Potent inhibition of drug-resistant HIV protease variants by monoclonal
      antibodies.
AB  - The monoclonal antibodies 1696 and F11.2.32 strongly inhibit the activity of wild
      type HIV-1 protease (PR) by binding to epitopes at the enzyme N-terminus
      (residues 1-6) and flap residues 36-46, respectively. Here we demonstrate that
      these antibodies are also potent inhibitors of PR variants resistant to active
      site inhibitors used as anti-AIDS drugs. Our in vitro experiments revealed that
      the inhibitory potency of single-chain fragments (scFv) of these antibodies is
      not significantly affected by the presence of mutations in PR; inhibition
      constants for drug-resistant protease variants are 5-11 nM and 13-169 nM for
      scFv1696 and for scFvF11.2.32, respectively. Tethered dimer of HIV-1 PR variant
      proved to be a model protease variant resistant to dissociative inhibition by
      1696, and, strikingly, it also displayed resistance to inhibition by F11.2.32
      suggesting that dimer dissociation also plays a role in the inhibitory action of
      F11.2.32.

PMID- 18329738
TI  - Protein kinase inhibitors of the quinazoline class exert anti-cytomegaloviral
      activity in vitro and in vivo.
AB  - Cytomegalovirus infection is associated with severe disease in immunocompromised
      individuals. Current antiviral therapy faces several limitations. In a search of
      novel drug candidates, we describe here the anti-cytomegaloviral properties of
      two compounds of the chemical class of quinazolines, gefitinib (Iressa) and
      Ax7396 (RGB-315389). Both compounds showed strong inhibitory effects in vitro
      against human and animal cytomegaloviruses with IC(50)s in a low micromolar
      range. Cytotoxicity did not occur at these effective concentrations. The
      antiviral mode of action was based on the inhibition of protein kinase activity,
      mainly directed to a viral target kinase (UL97/M97) in addition to cellular
      target candidates. This was demonstrated by a high sensitivity of the respective
      protein kinases in vitro and by infection experiments with viral mutants carrying
      genomic alterations in the ORF UL97/M97 modulating viral drug sensitivity. In a
      guinea pig model, gefitinib showed inhibition of cytomegaloviral loads in blood
      and lung tissue. Importantly, the rate of mortality of infected animals was
      reduced by gefitinib treatment. In contrast to the in vitro data, Ax7396 showed
      no significant antiviral activity in a mouse model. Further in vivo analyses have
      to assess the potential use of gefitinib in the treatment of cytomegalovirus
      disease.

PMID- 18329739
TI  - Occlusal tooth wear in male F344/N rats with aging.
AB  - With the aim of clarifying the aging properties of an animal model, the progress
      of occlusal tooth wear (OTW) of molars in male F344/N rats was monitored. Dried
      maxilla and mandible specimens from 61 male F344/N rats, aged 7 to >30 months,
      were used. The levels of OTW of all molars were monitored with aging. The cuspis
      dentis of molar teeth were worn out by 7 months (M) of age, and the occlusal
      surface became flat. As for each molar tooth (M(1-3), numbered in accordance with
      its position), OTW of M(1) was more severe in the lower than in the upper jaw,
      whereas M(3) was more severe in the upper than the lower jaw. OTW of M(2) in both
      the upper and the lower jaws progressed rapidly after 27M. OTW in male F344/N
      rats progressed faster than in females. However, when compensated for life span,
      both genders had similar profiles in OTW progress with aging. This study
      suggested that male rats were more convenient than females as a model for
      gerodontological research because of the earlier course of OTW progress.

PMID- 18329740
TI  - Isoproterenol enhancement of I(Ks) current in amiodarone-induced long QT
      syndrome.
AB  - The response over time of the QT interval and the Transmural Dispersion of
      Repolarization (TDR) to Isoproterenol infusion (ISO) in an 85 year-old-man with
      severe and syntomatic bradycardia, in the setting of an Amiodarone-induced Long
      QT Syndrome (LQTS) is the subject of this communication. ISO shortened the QT and
      decreased the TDR. We propose that ISO increased the generation of signals from
      the beta-Adrenergic Receptor (beta-AR) restoring the components of the hKCNQ1
      macromolecular complex, thereby enhancing the I(Ks) function; shortening of the
      QT interval, reduction of the TDR and normalization of the T wave morphology was
      then possible. In Amiodarone-induced LQTS, the increase in I(Ks) activity
      promoted by beta-AR stimulation is prominent; at the same time, during I(Kr)
      block, I(Ks) activation limits excessive QT prolongation. Clinically, severe and
      syntomatic bradycardia was the main concern: ISO activation of the beta-AR proved
      useful both to increase heart rate and to reduce QT prolongation. A slow heart
      rate, associated to a prolonged QT interval and to a big TDR, are not sufficient
      to develop Torsades de Pointes in Amiodarone-induced LQTS.

PMID- 18329741
TI  - Development of a SYBR safe technique for the sensitive detection of DNA in cesium
      chloride density gradients for stable isotope probing assays.
AB  - SYBR safe, a fluorescent nucleic acid stain, was evaluated as a replacement for
      ethidium bromide (EtBr) in cesium chloride (CsCl) density gradients for DNA
      stable isotope probing (DNA-SIP) assays. The separation of 12C- and 13C-labelled
      DNA using SYBR safe gave similar results to those obtained using EtBr with pure
      cultures and environmental samples exposed to a 13C-labelled substrate, while the
      detection limit of DNA was enhanced by the use of SYBR safe by at least 5 times.
      The results demonstrated that SYBR safe is a safe, sensitive and effective
      alternative to the use of ethidium bromide in CsCl density gradients for DNA-SIP
      assays.

PMID- 18329742
TI  - Potential improvement of tumor control probability by induction chemotherapy for
      advanced nasopharyngeal carcinoma.
AB  - PURPOSE: To assess the reduction of tumor bulk and improvement of tumor control
      probability (TCP) by using induction chemotherapy for advanced nasopharyngeal
      carcinoma (NPC). MATERIALS AND METHODS: From February to December 2005, 20
      patients with Stage III-IVB NPC were treated with induction-concurrent
      chemotherapy and intensity-modulated radiotherapy with accelerated fractionation.
      Combination of cisplatin and 5-fluorouracil was used in the induction phase and
      single agent Cisplatin in the concurrent phase. All patients were irradiated at
      2Gy per fraction, 6 daily fractions per week, to a total dose of 70Gy. RESULTS:
      Nineteen (95%) patients completed all 3 cycles of induction chemotherapy and 90%
      had 2 cycles of concurrent chemotherapy. Induction chemotherapy achieved
      significant down-staging of T-category in 35% of patients (p=0.016) and reduction
      of gross tumor volume (GTV_P) from 55.6 to 22.9cc (mean 61.4%, p<0.001). Although
      the mean radiation dose did not show any substantial change, the volume within
      GTV_P that failed to reach 70Gy was reduced from 10.2% to 3.8% (p=0.017). The
      estimated local TCP increased from 0.83 to 0.89 (p=0.002). CONCLUSIONS: Induction
      chemotherapy using cisplatin-5-fluorouracil could significantly reduce tumor bulk
      leading to potential improvement in tumor control.

PMID- 18329743
TI  - Cynicism, anger and cardiovascular reactivity during anger recall and human
      computer interaction.
AB  - Cynicism moderated by interpersonal anger has been found to be related to
      cardiovascular reactivity. This paper reports two studies; Study 1 used an Anger
      Recall task, which aroused interpersonal anger, while participants in Study 2
      engaged in a multitasking computer task, which aroused non-interpersonal anger
      via systematic manipulation of the functioning of the computer mouse. The
      Cynicism by State Anger interaction was significant for blood pressure arousal in
      Study 2 but not for Study 1: in Study 2, when State Anger was high, cynicism was
      positively related to blood pressure arousal but when State Anger was low,
      cynicism was negatively related to blood pressure arousal. For both studies, when
      State Anger was low, cynicism was positively related to cardiac output arousal
      and negatively related to vascular arousal. The results suggest that Cynicism
      State Anger interaction can be generalised to non-social anger-arousing
      situations for hemodynamic processes but blood pressure reactivity is task
      dependent. The implication for the role of job control and cardiovascular health
      during human-computer interactions is discussed.

PMID- 18329744
TI  - Maternal separation of rat pups increases the risk of developing depressive-like
      behavior after subsequent chronic stress by altering corticosterone and
      neurotrophin levels in the hippocampus.
AB  - Children that are abused have an increased risk for developing psychiatric
      disorders later in life, because of the negative effects of stress on the
      developing brain. We used a maternal separation model in rats to see how
      neurotrophins, stress hormones, behavior and the anti-oxidant potential of serum
      are affected. Rat pups were separated from their mothers for 3h/day on days 2-14.
      Maternal separation caused changes in levels of NGF and NT-3 in the dorsal and
      ventral hippocampus, increased basal corticosterone levels and decreased ACTH
      levels after acute restraint stress. The anti-oxidant potential of the rat serum
      was significantly lower in the maternal separation group. Depressive-like
      behavior, measured during a forced swim test, was seen in maternally separated
      rats after additional chronic stress during adulthood. Maternal separation caused
      downregulation of neurotrophins in the ventral hippocampus, possibly as an effect
      of high corticosterone levels, but compensatory mechanisms against cell death may
      be involved as neurotrophin levels increased in the dorsal hippocampus. Decreased
      anti-oxidant potential of serum could have been an effect of downregulated
      neurotrophin levels.

PMID- 18329745
TI  - In situ harvesting of adhered target cells using thermoresponsive substrate under
      a microscope: principle and instrumentation.
AB  - A novel technique and instrumented device were developed to harvest target cells
      from multicellular mixture of different cell types under a microscope. The
      principle of the technique is that cells cultured on a thermoresponsive-substance
      coated dish were detached by a region-specific cooling device and simultaneously
      harvested using a micropipette, both of which were assembled in an inverted
      microscope. Thermoresponsive coating consists of the mixture of poly(N
      isopropylacrylamide) (PNIPAAm) and PNIPAAm-grafted gelatin. The former non-cell
      adhesive polymer dissolves below at 32.1 degrees C in water and precipitates over
      that temperature (called lower critical solution temperature, LCST), and the
      latter cell-adhesive polymer has LCST of 34.1 degrees C. The appropriate mixing
      ratio of these thermoresponsive polymers exhibited high cell adhesion at
      physiological temperature and complete cell detachment at room temperature. A
      device developed as to cool at only a tiny area of the bottom of the dish,
      beneath which a cell that was targeted under a microscope, was assembled in a
      microscope. It was demonstrated that single cell or two cells that adhered to
      each other was detached from the surface and harvested by a micropipette within
      approximately 30s.

PMID- 18329746
TI  - Induction of apoptosis in Vero cells by Newcastle disease virus requires viral
      replication, de-novo protein synthesis and caspase activation.
AB  - Newcastle disease virus causes (NDV) apoptotic death of infected cells. In the
      present study, the stimulus that provoked the induction of apoptosis in infected
      cells was examined. Vero cells infected with NDV developed apoptosis as
      characterized by DNA fragmentation and decreased DNA content. In presence of
      ammonium chloride, infected cells did not show reduced DNA content indicating the
      requirement of virus entry for the induction of apoptosis. UV-inactivated NDV did
      not induce apoptosis in cells suggesting the need of virus replication. Although
      cycloheximide blocked NDV-induced apoptosis, actinomycin-D did not, suggesting
      that de-novo viral protein synthesis was critical for the induction of apoptosis.
      In addition, activation of caspases was also detected by flowcytometry, indirect
      fluorescent and colorimetric assays. Based on the results, it was concluded that
      NDV-induced apoptosis in Vero cells required virus replication, de-novo protein
      synthesis and caspase activation.

PMID- 18329747
TI  - Identification of amino acids in the HA of H3 influenza viruses that determine
      infectivity levels in primary swine respiratory epithelial cells.
AB  - In the late 1990s, triple reassortant H3N2 influenza A viruses emerged and spread
      widely within the swine population of the United States. We have shown previously
      that an isolate representative of this lineage of viruses,
      A/Swine/Minnesota/593/99 (Sw/MN), has higher infectivity and accelerated
      replication kinetics in pigs, compared to a human-lineage H3N2 virus isolated
      from a pig during the same time period, A/Swine/Ontario/00130/97 (Sw/ONT
      [Landolt, G.A., Karasin, A.I., Phillips, L., Olsen, C.W., 2003. Comparison of the
      pathogenesis of two genetically different H3N2 influenza A viruses in pigs. J.
      Clin. Microbiol. 41, 1936-1941]). Additional in vivo experiments using reverse
      genetics-generated reassortant viruses demonstrated that these phenotypes are
      dependent upon the HA and/or NA genes (Landolt, G.A., Karasin, A.I., Schutten,
      M.M., Olsen, C.W., 2006. Restricted infectivity of a human-lineage H3N2 influenza
      A virus in pigs is hemagglutinin and neuraminidase gene dependent. J. Clin.
      Microbiol. 44, 297-301). To further study the infectivity of influenza viruses
      for pigs, we developed a primary swine respiratory epithelial cell (SREC) culture
      model. In SRECs, Sw/MN infects a significantly higher number of cells compared to
      Sw/ONT. Using reverse genetics-generated Sw/MN x Sw/ONT reassortant viruses we
      demonstrate that the infectivity phenotypes of these viruses in SRECs are
      strongly dependent upon the HA gene. Using chimeras and point directed mutations
      within the HA genes, we have identified amino acids that, either alone or in
      combination with other amino acids, impact infectivity. In particular, amino acid
      138 is the dominant factor in determining infectivity levels in SRECs.

PMID- 18329748
TI  - Chimaeric HIV-1 subtype C Gag molecules with large in-frame C-terminal
      polypeptide fusions form virus-like particles.
AB  - HIV-1 Pr55 Gag virus-like particles (VLPs) are strong immunogens with potential
      as candidate HIV vaccines. VLP immunogenicity can be broadened by making
      chimaeric Gag molecules: however, VLPs incorporating polypeptides longer than 200
      aa fused in frame with Gag have not yet been reported. We constructed a range of
      gag-derived genes encoding in-frame C-terminal fusions of myristoylation
      competent native Pr55Gag and p6-truncated Gag (Pr50Gag) to test the effects of
      polypeptide length and sequence on VLP formation and morphology, in an insect
      cell expression system. Fused sequences included a modified reverse transcriptase
      Tat-Nef fusion polypeptide (RTTN, 778 aa), and truncated versions of RTTN ranging
      from 113 aa to 450 aa. Baculovirus-expressed chimaeric proteins were examined by
      western blot and electron microscopy. All chimaeras formed VLPs which could be
      purified by sucrose gradient centrifugation. VLP diameter increased with protein
      MW, from approximately 100 nm for Pr55Gag to approximately 250 nm for GagRTTN.
      The presence or absence of the Gag p6 region did not obviously affect VLP
      formation or appearance. GagRT chimaeric particles were successfully used in mice
      to boost T-cell responses to Gag and RT that were elicited by a DNA vaccine
      encoding a GagRTTN polypeptide, indicating the potential of such chimaeras to be
      used as candidate HIV vaccines.

PMID- 18329750
TI  - Lymph-node dissection for the treatment of lung cancer: sampling or complete
      nodal dissection?

PMID- 18329749
TI  - Hepatic gene expression and prediction of therapy response in chronic hepatitis C
      patients.
AB  - Chronic hepatitis C (HCV) infection remains a major health problem worldwide. The
      current standard of care is a combination of pegylated interferon-alpha and
      ribavirin. Considering the length of antiviral therapy, as well as its side
      effects and costs, accurate prediction of treatment response prior to initiation
      of treatment is critical. In addition to viral, demographic and environmental
      factors, host genetic diversity is believed to contribute to the spectrum of
      clinical outcomes of chronic HCV. The development of high-throughput technologies
      provides opportunities to define patterns of gene expression that are associated
      with certain disease outcomes and/or response to therapy. This article reviews
      genomics-based predictors of pre-treatment response to antiviral therapy.

PMID- 18329751
TI  - Synthesis and evaluation of a series of benzopyran derivatives as PPAR
      alpha/gamma agonists.
AB  - A series of benzopyran derivatives were synthesized and evaluated for PPAR
      alpha/gamma agonist activities. Most of the compounds exhibit reasonable PPAR
      alpha and PPAR gamma agonist activities. In particular, compounds 7b, 8b, 8e and
      8h with remarkable PPARg EC(50) values of 0.001microM are excellent full PPAR
      gamma agonists with the functional potency about 130, 20 times stronger than that
      of leading compound 5 and rosiglitazone, respectively. Compounds 7a, 7c, 7d and
      8a are dual PPAR alpha/gamma agonists, and all of them gave comparable or
      stronger PPAR alpha/gamma agonist efficacy than that of the corresponding
      positive control.

PMID- 18329752
TI  - Tryptophan-containing dipeptide derivatives as potent PPARgamma antagonists:
      design, synthesis, biological evaluation, and molecular modeling.
AB  - The discovery of peroxisome proliferator-activated receptor gamma (PPARgamma)
      antagonists (also termed "selective PPARgamma modulators, SPPARgammaM") is now of
      a great interest in the treatment of diabetes and obesity. The structure of
      compound 1a (G3335, Fig. 1), a novel class of PPARgamma antagonist, is entirely
      different from that of other reported PPARgamma antagonists. A series of 35 novel
      analogues (1b-l, 9a-d, 13a-t) were designed, synthesized and evaluated against
      the agonistic effects exerted by rosiglitazone. These results indicated that most
      functional groups of 1a were conserved, and six new compounds (1b, 1c, and 9a-d)
      exhibited strong PPARgamma antagonistic activities (IC(50) values of 5.2-25.8
      microM) against 10 microM rosiglitazone in the promotion of the PPARgamma-LBD-CBP
      (ligand-binding domain and cAMP-response-element binding protein) interaction as
      investigated by yeast two-hybrid technology based assay. Molecular modeling
      studies for compounds 1a-d, 1h, 9c-d, and 13a were also presented.

PMID- 18329753
TI  - Use of self-organizing maps and molecular descriptors to predict the cytotoxic
      activity of sesquiterpene lactones.
AB  - Some sesquiterpene lactones (SLs) are the active compounds of a great number of
      traditionally medicinal plants from the Asteraceae family and possess
      considerable cytotoxic activity. Several studies in vitro have shown the
      inhibitory activity against cells derived from human carcinoma of the nasopharynx
      (KB). Chemical studies showed that the cytotoxic activity is due to the reaction
      of alpha,beta-unsaturated carbonyl structures of the SLs with thiols, such as
      cysteine. These studies support the view that SLs inhibit tumour growth by
      selective alkylation of growth-regulatory biological macromolecules, such as key
      enzymes, which control cell division, thereby inhibiting a variety of cellular
      functions, which directs the cells into apoptosis. In this study we investigated
      a set of 55 different sesquiterpene lactones, represented by 5 skeletons (22
      germacranolides, 6 elemanolides, 2 eudesmanolides, 16 guaianolides and nor
      derivatives and 9 pseudoguaianolides), in respect to their cytotoxic properties.
      The experimental results and 3D molecular descriptors were submitted to Kohonen
      self-organizing map (SOM) to classify (training set) and predict (test set) the
      cytotoxic activity. From the obtained results, it was concluded that only the
      geometrical descriptors showed satisfactory values. The Kohonen map obtained
      after training set using 25 geometrical descriptors shows a very significant
      match, mainly among the inactive compounds (approximately 84%). Analyzing both
      groups, the percentage seen is high (83%). The test set shows the highest match,
      where 89% of the substances had their cytotoxic activity correctly predicted.
      From these results, important properties for the inhibition potency are discussed
      for the whole dataset and for subsets of the different structural skeletons.

PMID- 18329754
TI  - 6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new
      approach of the treatment of cancer cell invasion and metastasis.
AB  - Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were
      synthesized and their potency in reducing the invasive behaviour of HT 1080
      fibrosarcoma cells was evaluated. Structure-activity relationships were deduced
      from biological results and will be used in further design of new active
      compounds. In particular, the acetoxymethyl substituent found at the 6-position
      of previously described active compounds can be replaced by an acetamidomethyl
      substituent without loss of potency; while the presence of an aryl ester function
      at the 3-position was preferred to a thioester or an amide function to induce
      marked biological activity. This work confirms the interest of aryl esters of 6
      substituted coumarin-3-carboxylic acids as potential new anti-cancer agents.

PMID- 18329755
TI  - Different anthropometric index changes in relation to cardiovascular risk profile
      change.
AB  - BACKGROUND & AIMS: Different anthropometric indices were proposed to assess
      adiposity and its change in overweight children. The aim of this study was to
      identify the anthropometric index change that correlates best with cardiovascular
      risk factor change. METHODS: Lipids, insulin, blood pressure, body mass index
      (BMI), and skinfolds were measured among 434 overweight singletons aged 4-16
      years participating and not participating in an intervention program at baseline
      and 1 year later from 1999 to 2005. RESULTS: Mean BMI at baseline was 27.2
      kg/m(2) (standard error (SE) 0.2). A mean change at 1 year could be observed for
      weight (+5 kg; SE 0.32), BMI in standard deviation scores (SDS-BMI) (-0.2; SE
      0.02), and relative BMI (-0.7; SE 0.1). Eighteen percent of the children reduced
      their SDS-BMI> or =0.5, while 34% demonstrated an increase of SDS-BMI. The
      prediction of insulin-, insulin resistance index- and blood pressure changes by
      anthropometric differences ranged from 2% to 7% adjusted variance explained, and
      for changes of lipids<1%. Estimated %fat from skinfolds failed as a predictor.
      Goodness of prediction did not differ across the other anthropometric changes.
      CONCLUSIONS: No superior anthropometric predictor for the limited prediction of
      cardiovascular risk changes was observed among the considered parameters.
      Cardiovascular risk factors should be tracked to prove a cardiovascular effect of
      weight change and/or intervention.

PMID- 18329757
TI  - Enhancement of HIV DNA vaccine immunogenicity by the NKT cell ligand, alpha
      galactosylceramide.
AB  - A number of studies have shown that the natural killer T cell (NKT) ligand alpha
      galactosylceramide (alpha-GalCer) serves as an adjuvant for various vaccines,
      including viral vaccines, parasite vaccines and protein vaccines. In this report,
      we investigated the adjuvant activity of alpha-GalCer on HIV-1 DNA vaccines in
      mice. This is a first study to show that alpha-GalCer can enhance the
      immunogenicity of DNA vaccines, since co-administration of alpha-GalCer with
      suboptimal doses of DNA vaccines greatly enhanced antigen-specific CD4+ T-cell
      and CD8+ T-cell responses. Differently from other vaccines, alpha-GalCer was also
      able to enhance HIV-specific antibody response 10-fold. It is of practical
      importance to find out that, in a DNA prime-DNA boost regimen, the adjuvant
      activity of alpha-GalCer was most profound when co-administered at the priming,
      but not at the boosting phase. In a dose-sparing experiment, we found that the
      level of cell-mediated immune responses in mice vaccinated with 5 microg of DNA
      in the presence of alpha-GalCer was equivalent to that of mice vaccinated with 50
      microg of DNA in the absence of alpha-GalCer. Finally, results from CD1d and
      interferon-gamma receptor knockout mice confirm our previous data and determine
      the mechanistic dependence upon these molecules. These results illustrate that
      alpha-GalCer enhances the immunogenicity of DNA vaccines in a mechanism-based
      fashion. Since both mice and humans share the CD1d molecule, this information may
      aid in designing more effective DNA vaccines and vaccine adjuvants against HIV-1.

PMID- 18329758
TI  - Parent-collected respiratory specimens--a novel method for respiratory virus and
      vaccine efficacy research.
AB  - Population-based respiratory research and vaccine efficacy studies have
      previously required clinic or home visits when a subject had an acute respiratory
      illness. This method may mean parents are unwilling to enroll their child or
      report an illness of interest. We conducted a community-based cohort study into
      respiratory illnesses in 234 pre-school aged children using parent-collected
      specimens. Between January 2003 and January 2004 there were 563 specimens
      collected from 730 identified illnesses and these were tested using a panel of
      respiratory virus polymerase chain reaction (PCR) assays; 409 (73%) were positive
      for any virus. Specimens were not more likely to be positive when collected by a
      healthcare worker parent, when they included a throat swab, or when a very good
      collection technique was reported. A delay from illness onset to specimen
      collection of up to 5 days did not appear to impact on sensitivity of virus
      identification, but a delay of six or more days with minor delays in testing saw
      positivity fall. Combined with daily symptom diary completion and PCR testing,
      parent-collected specimens are an efficient and acceptable method for the conduct
      of future vaccine efficacy studies and other community-based respiratory virus
      research.

PMID- 18329759
TI  - Immunization with virus-like particles of enterovirus 71 elicits potent immune
      responses and protects mice against lethal challenge.
AB  - Enterovirus 71 (EV71) is an etiologic agent responsible for seasonal epidemics of
      hand-foot-and-mouth disease and causes outbreaks with significant mortality among
      young children. To develop the vaccine, we have produced and purified the EV71
      virus-like particle (VLP) that resembles the authentic virus in appearance,
      capsid structure and protein composition. In this study, we further evaluated the
      potential of VLP as a vaccine by comparing the humoral and cellular immune
      responses elicited by the purified VLP, denatured VLP and heat-inactivated EV71
      virus. After immunization of BALB/c mice, EV71 VLP induced potent and long
      lasting humoral immune responses as evidenced by the high total IgG titer and
      neutralization titer. The splenocytes collected from the VLP-immunized mice
      exhibited significant cell proliferation and produced high levels of IFN-gamma,
      IL-2 and IL-4 after stimulation, indicating the induction of Th1 and Th2 immune
      responses by VLP immunization. More importantly, the VLP immunization of mother
      mice conferred protection (survival rate up to 89%) to neonatal mice against the
      lethal (1000 LD(50)) viral challenge. Compared with the VLP immunization,
      immunization with denatured VLP and heat-inactivated EV71 elicited lower
      neutralization titers and conferred less effective protection to newborn mice,
      although they induced comparable levels of total IgG and cellular immune
      responses. These data collectively indicate the importance of the preservation of
      VLP structure and implicate the potential of VLP as a vaccine to prevent EV71
      infection.

PMID- 18329760
TI  - Age-dependent tolerance to an endogenous tumor-associated antigen.
AB  - Immunologic tolerance to endogenous antigens reduces antitumor responses. Gp70 is
      an endogenous tumor-associated antigen (TAA) of the BALB/c-derived colon
      carcinoma CT26. We found that expression of gp70 mRNA is detectable in tissues of
      mice 8 months of age and older. We showed that expression of gp70 establishes
      immunologic tolerance and affects antitumor immunity in a similarly age-dependent
      manner using gp70-deficient mice. We found that tumors grew in all gp70
      sufficient mice, while approximately half of gp70-deficient mice controlled tumor
      growth with endogenous T-cell responses. Protection in gp70-deficient mice
      correlated with more robust gp70-specific CTL responses, and increased numbers
      and avidity of responding antigen-specific T cells after vaccination. We conclude
      that immunosurveillance may decline with age due to increased or de novo
      peripheral expression of endogenous TAAs.

PMID- 18329761
TI  - Horizontal transmission of the Leningrad-Zagreb mumps vaccine strain: a report of
      three cases.

PMID- 18329762
TI  - The protective efficacy against Schistosoma japonicum infection by immunization
      with DNA vaccine and levamisole as adjuvant in mice.
AB  - Levamisole (LMS) as an adjuvant enhances cell-mediated immunity in DNA
      vaccination; we investigated the efficacy and liver immunopathology alleviation
      of a DNA vaccine, VR1012-SjGST-32, in a LMS formulation in the murine challenge
      model. Compared to controls, the VR1012-SjGST-32 plus LMS can reduce worm and egg
      burdens, as well as, immunopathological complications associated chronic
      inflammation significantly in liver, which were apparently associated with Th1
      type response. Together, these results suggest that the LMS as a potential
      Schistosome DNA vaccine adjuvant can enhance both worm killing and disease
      prevention, which is possibly mediated through the induction of a strong Th1
      dominant environment in immunized mice.

PMID- 18329763
TI  - Oral administration of a Bacillus subtilis spore-based vaccine expressing
      Clonorchis sinensis tegumental protein 22.3 kDa confers protection against
      Clonorchis sinensis.
AB  - Human clonorchiasis, caused by the infection of Clonorchis sinensis, is endemic
      in China. In this study, a full-length cDNA sequence encoding C. sinensis
      tegumental protein 22.3 kDa (CsTP22.3) was identified from adult cDNA library.
      Recombinant CsTP22.3 was expressed and purified from Escherichia coli BL21.
      CsTP22.3 was immunolocalized at the tegument of adult C. sinensis by using anti
      recombinant CsTP22.3 sera. ELISA was performed using rCsTP22.3 protein to
      investigate the IgG response to CsTP22.3. Sera from clonorchiasis patients had
      clear IgG response to CsTP22.3. We used the CotC, a major component of the
      Bacillus subtilis spore coat, as a fusion partner for the expression of C.
      sinensis TP22.3 on the spore coat. Western blotting and immunofluorescence
      analyses were used to identify TP22.3 surface expression on spores. Recombinant
      spores displaying the TP22.3 antigen were used for oral immunization and were
      shown to generate mucosal response in rats. TP22.3-specific secretory IgA in
      faeces reached significant levels 2 weeks after oral dosing. In addition, the
      recombinant spores induced a significant level of protection (44.7%, p<0.05) in
      rats challenged with C. sinensis metacercariae. This report shows that C.
      sinensis TP22.3 expressed on B. subtilis spores was immunogenic and oral
      administration of TP22.3 spore can provide protection against C. sinensis.

PMID- 18329764
TI  - Cross-protective immunity conferred by a DNA adenine methylase deficient
      Salmonella enterica serovar Typhimurium vaccine in calves challenged with
      Salmonella serovar Newport.
AB  - Intensive livestock production and management systems are associated with
      increased fecal-oral pathogen transmission and a resultant high prevalence of
      multiple Salmonella serovars in many large dairy farms and feedlots. Thus, it is
      imperative to develop livestock vaccines that are capable of eliciting potent
      states of cross-protective immunity against a diversity of serovars of a given
      species. Immunization with modified live Salmonella enterica serovar Typhimurium
      vaccine strains, that lack the DNA adenine methylase (Dam), confers cross
      protective immunity in murine and avian models of typhoid fever as well as in a
      bovine model of salmonellosis. Here we examined whether a dam mutant Typhimurium
      vaccine (serogroup B) has the capacity to elicit cross-protection against a
      virulent challenge with an emerging, clinically relevant, and multi-drug
      resistant strain of serovar Newport (serogroup C2-C3) that has been associated
      with clinical disease in recent salmonellosis outbreaks in calves. Vaccinated
      animals challenged with Newport exhibited a significant attenuation of clinical
      disease (improved attitude scores, increased daily weight gains and reduced fever
      and diarrhea) and a concomitant reduction in Newport fecal shedding and
      colonization of mesenteric lymph nodes and lungs compared to non-vaccinated
      control animals. The capacity to elicit cross-protective immunity in calves
      suggests that dam mutant vaccines have potential application toward the
      prevention and control of Salmonella infection in commercial livestock production
      systems wherein livestock are exposed to a diversity of Salmonella serovars.

PMID- 18329765
TI  - The ERICA Tool.
AB  - The ERICA Tool is a computerised, flexible software system that has a structure
      based upon the ERICA Integrated Approach to assessing the radiological risk to
      biota. The Tool guides the user through the assessment process, recording
      information and decisions and allowing the necessary calculations to be performed
      to estimate risks to selected animals and plants. Tier 1 assessments are media
      concentration based and use pre-calculated environmental media concentration
      limits to estimate risk quotients. Tier 2 calculates dose rates but allows the
      user to examine and edit most of the parameters used in the calculation including
      concentration ratios, distribution coefficients, percentage dry weight soil or
      sediment, dose conversion coefficients, radiation weighting factors and occupancy
      factors. Tier 3 offers the same flexibility as Tier 2 but allows the option to
      run the assessment probabilistically if the underling parameter probability
      distribution functions are defined. Results from the Tool can be put into context
      using incorporated data on dose-effects relationships and background dose rates.

PMID- 18329766
TI  - Arthroscopy with open surgery for treatment of synovial chondromatosis of the
      temporomandibular joint.
AB  - We report a case of synovial chondromatosis of the temporomandibular joint in
      which both joint compartments were affected. Because of the important involvement
      of the medial aspect of the joint, arthrotomy was done with arthroscopic
      assistance.

PMID- 18329767
TI  - Reconstruction of post-orthognathic aseptic necrosis of the maxilla.
AB  - We present the reconstruction of near total aseptic necrosis of the maxillary
      alveolus that occurred after a Le Fort I osteotomy eight years previously.

PMID- 18329768
TI  - Perfluorinated and chlorinated pollutants as predictors of demographic parameters
      in an endangered seabird.
AB  - Despite global occurrence of several perfluorinated compounds (PFCs) the
      potential ecological effects of such substances on natural populations are not
      known. In endangered lesser black-backed gulls (Larus fuscus fuscus) on the
      Norwegian Coast, the blood concentrations of PFCs were as high as legacy
      organochlorines (OCs), and here we examined whether PFCs show associations
      similar to those of OCs to factors potentially affecting population growth, by
      evaluating relationships between contaminant concentrations and demographic
      parameters (reproductive performance and the probability of adults returning
      between breeding seasons). PFCs were not adversely associated with demographic
      parameters, while the most persistent OCs; notably PCB and p,p'-DDE, were
      adversely associated with early chick survival, and adult return rate. This study
      thus suggests that when the concentrations of PFCs and OCs are of similar
      magnitude in a gull population, OCs are more likely to cause adverse ecological
      effects.

PMID- 18329769
TI  - Total mercury, organic mercury and selenium in liver and kidney of a South
      American coastal dolphin.
AB  - Selenium and total and organic mercury were determined in the liver and kidney of
      franciscana dolphin (Pontoporia blainvillei) incidentally caught in fishing nets
      along two Brazilian coastal areas (southeast and south). Regional differences in
      the concentrations of these contaminants were observed in P. blainvillei. Liver
      showed the highest organic and total mercury. In general, samples of individuals
      collected at the southern of Brazil had the highest concentrations of selenium
      and total and organic mercury. No significant gender differences were observed.
      Growth stage influenced the accumulation of these contaminants in both organs,
      and hepatic concentrations increased with the body length, according to the
      sampling area. Molar mercury and selenium concentrations in liver were
      significantly correlated, with a Se:Hg ratio close to 4. The among-site
      differences we found may be related to differences in preferred prey,
      bioavailability in the marine environment, environmental conditions, or these
      individuals may belong to distinct populations.

PMID- 18329770
TI  - Effects of a brine discharge over soft bottom Polychaeta assemblage.
AB  - Desalination is a growing activity that has introduced a new impact, brine
      discharge, which may affect benthic communities. Although the role of polychaetes
      as indicators to assess organic pollution is well known, their tolerance to
      salinity changes has not been examined to such a great extent. The aim of this
      study was to examine the effect of brine discharge over soft bottom polychaete
      assemblage along the Alicante coast (Southeast Spain) over a two year period.
      Changes in the polychaete assemblage was analysed using univariate and
      multivariate techniques. We compared a transect in front of the discharge with
      two controls. At each transect we sampled at three depths (4, 10 and 15 m) during
      winter and summer. We have observed different sensitivity of polychaete families
      to brine discharges, Ampharetidae being the most sensitive, followed by
      Nephtyidae and Spionidae. Syllidae and Capitellidae showed some resistance
      initially, while Paraonidae proved to be a tolerant family.

PMID- 18329771
TI  - Whatever happened to symptom substitution?
AB  - Symptom substitution is a theoretical consequence of the psychodynamic model of
      psychopathology and symptom formation that contrasts markedly with behavioral
      models. Symptom substitution was a major scientific and clinical question about a
      half century ago that was abandoned rather than answered partly because it did
      not seem to occur and partly because perceived methodological problems impeded
      empirical research. The contemporary relevance of symptom substitution is that
      the psychodynamic model of psychopathology and symptom formation from which the
      prediction of symptom substitution stems continues to be widely taught and to
      broadly inform clinical practice. This article revisits the psychodynamic model
      of symptom formation and substitution, restates perceived methodological
      limitations to its empirical study, demonstrates that symptom substitution is an
      empirically testable prediction, reviews the relevant empirical literature, and
      discusses implications for the science and practice of clinical psychology
      including a proposed research design for certifying bona fide psychoanalytic
      symptoms.

PMID- 18329772
TI  - Eating patterns may mediate the association between marital status, body mass
      index, and blood cholesterol levels in apparently healthy men and women from the
      ATTICA study.
AB  - Marital status has been recognized as a significant health-influencing factor,
      including cardiovascular disease (CVD) risk. The aim of the present paper was to
      evaluate whether eating habits mediate the relationship between marital status
      and levels of CVD risk factors among apparently healthy men and women from the
      ATTICA Study. During 2001-2002, we randomly enrolled 1514 men (18-87 years old)
      and 1528 women (18-89 years old) from the Attica area, Greece; the sampling was
      stratified by the age-gender distribution of the region. Participants underwent
      clinical, anthropometric and psychological assessment. Food consumption was
      assessed through a semi-quantitative food frequency questionnaire. Participants
      were classified as never married, married, divorced and widowed. Discriminant
      analysis revealed that vegetable consumption, followed by red meat, potatoes,
      poultry, and soft drinks were the factors with the higher discriminating ability
      among the food groups studied. In particular, dietary patterns of never married
      participants were characterized by the consumption of potatoes and red meat,
      those of married participants by nuts, legumes and fish, those of divorced
      participants by fruits, cereals and soft drinks, whereas those of widowed
      participants by dairy, vegetables, sweets and poultry. In addition, never married
      and divorced participants reported eating fast-foods more frequently and drink
      less alcohol compared to married or widowed participants. After controlling for
      potential confounders (i.e., age, gender, physical activity, anxiety score and
      smoking habits), the reported marital status of the participants was associated
      only with body mass index and total serum cholesterol levels. When the analysis
      was repeated after taking into account the information on dietary habits by
      creating four "new" dietary-adjusted marital status groups, no significant
      association was revealed between marital status and body mass index and blood
      cholesterol levels. This finding implies that, in our population, eating patterns
      may explain the observed differences between marital status and selected CVD risk
      factors.

PMID- 18329773
TI  - When to seek health care: a duration analysis for malaria patients in Nepal.
AB  - We find that the log-normal distribution of care-seeking time - the number of
      days from the onset of symptoms of malaria to when a patient seeks treatment from
      a provider - best described the treatment-seeking behavior of malaria patients in
      rural areas of two districts of Nepal. The care-seeking rate, or the probability
      of seeking care, was low on the first day of the symptoms; it increased sharply
      over the first five days and then gradually declined. Since at the time of the
      research there was a system of malaria workers taking monthly surveillance rounds
      of each house to detect and treat malaria cases, patients, instead of traveling
      to a provider for care, generally waited for malaria workers to arrive at home
      when the wait for malaria workers was short. But, the probability of seeking care
      on any day rose if the wait was longer. Women generally tended to wait longer for
      the malaria workers in order to receive treatment at home. Patient's age,
      household size, education, and the type of malaria species infecting the patient
      had no significant effect on care-seeking rate. Given an assumption that a wait
      of 100 days for a malaria worker would effectively represent total absence of
      surveillance program, the estimated model predicted higher care-seeking rates
      under no surveillance program than under the monthly surveillance program.

PMID- 18329774
TI  - Scaling-up antiretroviral treatment in Southern African countries with human
      resource shortage: how will health systems adapt?
AB  - Scaling-up antiretroviral treatment (ART) to socially meaningful levels in low
      income countries with a high AIDS burden is constrained by (1) the continuously
      growing caseload of people to be maintained on long-term ART; (2) evident
      problems of shortage and skewed distribution in the health workforce; and (3) the
      heavy workload inherent to presently used ART delivery models. If we want to
      imagine how health systems can react to such challenges, we need to understand
      better what needs to be done regarding the different types of functions ART
      requires, and how these can be distributed through the care supply system,
      knowing that different functions rely on different rationales (professional,
      bureaucratic, social) for which the human input need not necessarily be found in
      formal healthcare supply systems. Given the present realities of an increasingly
      pluralistic healthcare supply and highly eclectic demand, we advance three main
      generic requirements for ART interventions to be successful: trustworthiness,
      affordability and exclusiveness--and their constituting elements. We then apply
      this analytic model to the baseline situation (no fundamental changes) and
      different scenarios. In Scenario A there are no fundamental changes, but ART gets
      priority status and increased resources. In Scenario B the ART scale-up
      strengthens the overall health system: we detail a B1 technocratic variant
      scenario, with profoundly re-engineered ART service production, including
      significant task shifting, away from classical delivery models and aimed at
      maximum standardisation and control of all operations; while in the B2 community
      based variant scenario the typology of ART functions is maximally exploited to
      distribute the tasks over a human potential pool that is as wide as possible,
      including patients and possible communities. The latter two scenarios would
      entail a high degree of de-medicalisation of ART.

PMID- 18329775
TI  - Accumulation and depuration of the synthetic antioxidant ethoxyquin in the muscle
      of Atlantic salmon (Salmo salar L.).
AB  - The biological fate of the fish feed additive, ethoxyquin (EQ) was examined in
      the muscle of Atlantic salmon during 12 weeks of feeding followed by a 2 weeks
      depuration period. Parent EQ (1,2-dihydro-6-ethoxy-2,2,4-trimethylquinoline),
      quinone imine (2,6-dihydro-2,2,4-trimethyl-6-quinolone), de-ethylated EQ (6
      hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline) and EQDM (EQ dimer or 1,8'-di(1,2
      dihydro-6-ethoxy-2,2,4-trimethyl-quinoline) were found to be the ubiquitous
      metabolites of dietary EQ, with EQDM as a main metabolite. A rapid decrease in
      the level of EQ (2.4 days of half-life) was balanced by an increase in EQDM,
      giving an unchanged net sum following 2 weeks of depuration. The mandatory 14
      days depuration period prior to slaughtering of farmed salmon in Norway was not
      sufficient for complete elimination of EQ-derived residuals. Post depuration,
      EQDM accounted for 99% of sum of the two compounds in all treatment groups;
      possible toxicological effects of EQDM are not known. The individual
      concentrations of EQ and EQDM and their sum are dependent on EQ level in the
      feed, consequently, their residual concentrations may be controlled. The
      theoretical amount of EQ and EQDM consumed in one meal of farmed salmon would be
      under the recommended ADI, provided that the fish were raised on feed with no
      more than 150 mg EQ/kg feed, which is the EU maximum limit for EQ in fish feed.

PMID- 18329776
TI  - Genotoxicity of low dose N-nitroso propoxur to human gastric cells.
AB  - Propoxur is among the most popular insect control agents in subtropical countries
      such as Taiwan. As a member of the N-methylcarbamate insecticide group, propoxur
      is notorious for its potential for conversion into highly genotoxic N-nitroso
      derivatives. Due to the fact that the stomach has been identified as the major
      target for N-nitroso N-methylcarbamates, this investigation used a human gastric
      cell line, SC-M1, in order to obtain results pertinent to the authentic adverse
      effects of this compound on human health. This report reveals that at dose levels
      inhibiting < or = 10% cell growth, a 2-h pulsed treatment of N-nitroso propoxur
      induced significant amounts of DNA damage. Most of the damaged DNA was repaired
      within 24 h after treatment removal, such that an outcome with a significant
      induction of chromosomal aberrations was not observed. Gene mutations and
      anchorage independence, on the other hand, were significantly induced by this
      same treatment. In conclusion, exposure to low doses of N-nitroso propoxur is not
      cytotoxic nor clastogenic, nevertheless, has the potential to increase genetic
      instability and, possibly as a result, to enhance the malignant potential of
      treated cells. We suggest that although the damaged DNA was repaired during the
      transient G2/M arrest period, it was probably not done in an appropriate way
      which would preserve the original genetic stability.

PMID- 18329777
TI  - Bioaccessibility of essential and non-essential metals in commercial shellfish
      from Western Europe and Asia.
AB  - Maximum acceptable concentrations of metals in food - based on total
      concentrations - have been established in many countries. To improve risk
      assessment, it would be better to take into account bioaccessible concentrations.
      A total of seven species of molluscs from France, UK and Hong Kong was examined
      in this study including clams, mussels, oysters, scallops and gastropods. The
      species which have total metal concentrations higher than the most severe food
      security limits are mainly oysters (all of the three studied species), the
      gastropod Buccinum undatum for cadmium and zinc, and scallops for cadmium. The
      lowest bioaccessibility (in % extractability with gut juices) was observed for
      silver (median for all of the species: 14%), it was moderate for lead (median:
      33%) and higher for cadmium, zinc and copper (medians were respectively 54%, 65%,
      and 70%). In most cases, bioaccessible concentrations remained higher than the
      safety limits, except for cadmium in scallops and zinc in B. undatum. The
      influence of feeding habit (masticated or swallowed, addition of vinegar or
      lemon) on metal bioaccessibility in oysters is limited. On the contrary, cooking
      the gastropods decreased the bioaccessibility of metals, except silver.

PMID- 18329778
TI  - Lipid metabolism in liver of rat exposed to cadmium.
AB  - We investigated the effect of exposition to cadmium (Cd, 15ppm for 8 weeks)
      through drinking water on liver lipid metabolism in adult male Wistar rats. As
      compared to metal non-exposed (control) rats, the serum triglycerides,
      cholesterol and LDL+VLDL cholesterol concentrations increased. This was
      associated to a decrease of lipoprotein lipase activity in post heparinic plasma.
      The VLDL secretion from liver was not modified. Cd treatment increased
      triglycerides and decreased esterified cholesterol contents in liver. The high
      triglyceride mass was related to the increased glycerol-3-phosphate
      acyltransferase mRNA expression. In addition, the liver fatty acids synthesis
      increased, as determined by an increment of fatty acid synthetase and isocitrate
      dehydrogenase activities, and [(14)C]-acetate incorporation into saponifiable
      lipid fraction. The relative percentage of palmitic acid (16:0) and total
      saturated fatty acids were increased compared with control. Hepatic glucose-6
      phosphate dehydrogenase, malic dehydrogenase and cholesteryl ester hydrolase
      activities were unchanged. In liver, the Cd treatment decreased triglyceride and
      cholesterol in mitochondria, also increased triglyceride in cytosol, and
      cholesterol and phospholipid contents in nuclei, compared with control. In
      addition, an increase of nuclei phosphatidylcholine synthesis was observed. Cd
      exposure alters directly or indirectly the serum lipid content and liver lipid
      metabolism.

PMID- 18329779
TI  - Brain imaging, genetics and emotion.
AB  - This paper reviews the published evidence on genetically driven variation in
      neurotransmitter function and brain circuits involved in emotion. Several studies
      point to a role of the serotonin transporter promoter polymorphism in amygdala
      activation during emotion perception. We also discuss other polymorphisms (e.g.
      the COMT val158met polymorphism, tryptophan hydroxylase-2 -703 G/T) and putative
      effects on affective processing in cortical and limbic regions. A different line
      of research concerns studies with genetic disorders. Although at a less fine
      grained level, studies with individuals with aneuploidies of the X chromosome
      (Turner syndrome and Klinefelter syndrome), who display impairments in emotion
      processing, have resulted in new insights and hypotheses with regard to X
      chromosomal influences on brain systems supporting cognition and emotion. These
      have also implicated a key role for the amygdala. Integration of the emerging
      evidence, suggests that the study of polymorphisms using brain imaging can
      potentially elucidate biological pathways and mechanisms contributing to
      individual differences in brain circuits that may bias behavior and affect risk
      for psychiatric illness.

PMID- 18329781
TI  - Thermomyces lanuginosus lipase in the liquid-crystalline phases of aqueous
      phytantriol: X-ray diffraction and vibrational spectroscopic studies.
AB  - The influence of Thermomyces lanuginosus lipase (TLL) on the phase behaviour of
      liquid-crystalline phases of aqueous phytantriol as well as conformational
      changes of TLL entrapped in the cubic Q230 phase have been studied by small angle
      X-ray diffraction (SAXD), FT-Raman, and FT-IR techniques. It was found that the
      lipidic Q230 phase is able to accommodate up to 10 wt.% of TLL, and the
      temperature of phase transition to the inverted hexagonal phase H(II) increases
      indicating stabilizing effect of the protein. FT-Raman analysis of Trp amino acid
      marker band W3 revealed that the average rotation angle around the C3-Cbeta bond
      of four Trp residues of TLL in the Q230 phase increases. Reasoning from available
      TLL crystallographic data, this result is explained by structural transition of
      entrapped protein to so-called "open" and more related to the enzymatically
      active conformation. TLL secondary structure analysis by amide I and amide III
      vibrational bands showed that content of alpha-helixes does not change, while a
      part of beta-sheet structures transforms to less ordered elements upon
      incorporation of protein into the Q230 phase of aqueous phytantriol.

PMID- 18329782
TI  - Autolysis loop restricts the specificity of activated protein C: analysis by FRET
      and functional assays.
AB  - We previously demonstrated that the substitution of the autolysis loop (residues
      143-154 in chymotrypsin numbering) of APC with the corresponding loop of trypsin
      (APC-Tryp 143-154) has no influence on the proteolytic activity of the protease
      toward fVa, however, this substitution increases the reactivity of APC with
      plasma inhibitors so that the mutant exhibits no anticoagulant activity in
      plasma. To further investigate the role of the autolysis loop in APC and
      determine whether this loop is a target for modulation by protein S, we evaluated
      the activity of APC-Tryp 143-154 toward fVa and several plasma inhibitors both in
      the absence and presence of protein S. Furthermore, we evaluated the active-site
      topography of APC-Tryp 143-154 by determining the average distance of the closest
      approach (L) between a fluorescein dye tethered to a tripeptide inhibitor,
      attached to the active-site of APC-Tryp 143-154, and octadecylrhodamine dyes
      incorporated into PCPS vesicles both in the absence and presence of protein S.
      The activity of APC-Tryp 143-154 toward fVa was identical to that of wild-type
      APC both in the presence and absence of protein S. However, the reactivity of APC
      Tryp 143-154 with plasma inhibitors was preferentially improved independent of
      protein S. The FRET analysis revealed a dramatic change in the active-site
      topography of APC both in the absence and presence of protein S. Anisotropy
      measurements revealed that the fluorescein dye has a remarkable degree of
      rotational freedom in the active-site of APC-Tryp 143-154. These results suggest
      that the autolysis loop of APC may not be a target for modulation by protein S.
      This loop, however, plays a critical role in restricting both the specificity and
      spatial environment of the active-site groove of APC.

PMID- 18329783
TI  - Methylation in methanol-water mixtures: the effect of solvent composition and
      high pressure.
AB  - The effect of pressure (0.1 to 400 MPa) and solvent composition (methanol
      concentration of 5 to 30%) on the synthesis of beta-methylgalactoside was
      studied. Galactose was used as a reactant and the reaction was catalyzed by beta
      galactosidase from Aspergillus oryzae. Under the applied conditions the enzyme
      was sufficiently stable and the reaction equilibrium was reached. Higher methanol
      concentrations obviously influenced the product yield positively due to an
      increase in reactant concentration but also due to a solvent effect. This solvent
      effect can be explained by measurement of the activities of galactose and
      methylgalactoside. These results may be generalized to other methylations in
      methanol-water systems, where methanol positively affects synthesis yields.
      Pressure had a small, negative effect on synthesis yields.

PMID- 18329784
TI  - The driving force behind genomic diversity.
AB  - Eukaryote genomes contain excessively introns, intergenic and other non-genic
      sequences that appear to have no vital functional role or phenotype
      manifestation. Their existence, a long-standing puzzle, is viewed from the
      principle of increasing entropy. According to thermodynamics of open systems,
      genomes evolve toward diversity by various mechanisms that increase, decrease and
      distribute genomic material in response to thermodynamic driving forces.
      Evolution results in an excessive genome, a high-entropy ecosystem of its own,
      where copious non-coding segments associate with low-level functions and
      conserved sequences code coordinated activities. The rate of entropy increase,
      equivalent to the rate of free energy decrease, is identified with the universal
      fitness criterion of natural selection that governs populations of genomic
      entities as well as other species.

PMID- 18329785
TI  - Inoculation of plant growth promoting bacterium Achromobacter xylosoxidans strain
      Ax10 for the improvement of copper phytoextraction by Brassica juncea.
AB  - In this study, a copper-resistant plant growth promoting bacterial (PGPB) strain
      Ax10 was isolated from a Cu mine soil to assess its plant growth promotion and
      copper uptake in Brassica juncea. The strain Ax10 tolerated concentrations up to
      600 mg CuL(-1) on a Luria-Bertani (LB) agar medium and utilized 1
      aminocyclopropane-1-carboxylic acid (ACC) as a sole N source in DF salts minimal
      medium. The strain Ax10 was characterized as Achromobacter xylosoxidans based on
      its 16S rDNA sequence homology (99%). The bacterium A. xylosoxidans Ax10 has also
      exhibited the capability of producing indole acetic acid (IAA) (6.4 microg mL(
      1)), and solubilizing inorganic phosphate (89.6 microg mL(-1)) in specific
      culture media. In pot experiments, inoculation of A. xylosoxidans Ax10
      significantly increased the root length, shoot length, fresh weight and dry
      weight of B. juncea plants compared to the control. This effect can be attributed
      to the utilization of ACC, production of IAA and solubilization of phosphate.
      Furthermore, A. xylosoxidans Ax10 inoculation significantly improved Cu uptake by
      B. juncea. Owing to its wide action spectrum, the Cu-resistant A. xylosoxidans
      Ax10 could serve as an effective metal sequestering and growth promoting
      bioinoculant for plants in Cu-stressed soil. The present study has provided a new
      insight into the phytoremediation of Cu-contaminated soil.

PMID- 18329786
TI  - Phosphodiesterase type 5 inhibitors improve male lower urinary tract symptoms.

PMID- 18329787
TI  - Rebuttal from authors re: James W.F. Catto. More nomograms or better evidence of
      efficacy: what do we need in urologic oncology? Eur Urol 2008;54:11-12.

PMID- 18329788
TI  - Aneurysm at the fenestrated anterior cerebral artery: surgical anatomy and
      management.
AB  - The authors report a rare case of an aneurysm arising at fenestrated anterior
      cerebral artery. The embryogenesis of this anatomical variation is discussed
      along with the review of relevant literature. Management of such lesions depends
      upon the location and morphology of the aneurysms and intracranial vascular
      anatomy. The authors discuss various management options and highlight possible
      technical difficulties that can be encountered in the surgical management of this
      rare sub-group of aneurysms.

PMID- 18329789
TI  - Apoptotic DNA fragments in serum of patients with muscle invasive bladder cancer:
      a prognostic entity.
AB  - Patients with malignancies often possess increased concentrations of cell-free
      serum DNA. In this study, we investigated serum DNA levels in each 45 patients
      with bladder cancer (BCA) undergoing radical cystectomy and with benign prostate
      hyperplasia. A quantitative real-time PCR was used to amplify a 124 bp (PTGS2;
      mostly apoptotic origin) and a 271 bp (Reprimo; mostly necrotic origin) DNA
      fragment. Changes in the origin of DNA fragments were specified as the Apoptosis
      Index (AI, ratio of 124 bp/271 bp fragments). Small and large fragments were
      increased (p<0.001 and p=0.041) in BCA patients. The AI increase suggests that
      DNA fragmentation was mostly (p<0.001) caused by apoptosis. High levels of small
      DNA fragments distinguished between BCA and BPH with high sensitivity (96%) and
      moderate specificity (62%). DNA levels and the AI were not correlated with
      clinicopathological parameters. However, an increased AI was correlated with BCA
      specific mortality in a multivariate analysis (p=0.011) indicating that the AI is
      an independent prognostic factor. Thus, cell-free DNA seems to be a useful
      prognostic marker in patients with BCA.

PMID- 18329790
TI  - High-LET radiation combined with oxaliplatin induce autophagy in U-87
      glioblastoma cells.
AB  - Modern protocols of concomitant chemo/radiotherapy provide a very effective
      strategy to treat certain types of tumors. High-linear energy transfer (LET)
      radiations, on the other hand, have an increased efficacy against cancer with low
      radiosensibility and critical localization. We previously reported that
      oxaliplatin, a third generation platinum drug, was able to reinforce the
      cytotoxicity of an irradiation by fast neutrons towards human glioblastoma U-87
      cells in culture. We show here that such a combination has the capacity to
      enhance the number of double strand breaks in DNA and to induce autophagy in
      these cells. Xenografts experiments were further performed in nude mice
      subcutaneously transplanted with U-87 cells. When injected shortly before a
      single irradiation by fast neutrons, oxaliplatin causes a marked reduction of
      tumor growth compared with the irradiation alone. Overall, our data indicate the
      unique cytotoxic mechanism of a combined high-LET irradiation and oxaliplatin
      treatment modality and suggest its potential application in anticancer therapy.

PMID- 18329791
TI  - Gene expression profiling to identify genes associated with high-invasiveness in
      human squamous cell carcinoma with epithelial-to-mesenchymal transition.
AB  - The process of epithelial-to-mesenchymal transition (EMT) involves the
      acquisition of high-invasiveness by tumor. Snail represses target genes and
      induces EMT. In this study, we defined the signatures of gene expressions by cDNA
      microarray analyses in both human squamous cell carcinoma (SCC) cell lines with
      spontaneous EMT and with Snail-induced EMT, which exhibited high-invasive
      behavior in vitro. Of the 17,000 cDNA probes, 61 genes were found differentially
      expressed with >2- or <0.5-fold ratio and shared among the EMT phenotype cell
      lines, indicating candidates for invasion-associated genes regulated by Snail.
      Category analysis showed that these genes were mainly classified as
      development/differentiation, metabolism, apoptosis, angiogenesis and cell
      adhesion. These data illustrated that Snail regulates various molecular pathways
      for the establishment of EMT and the acquisition of high-invasiveness in SCC
      cells, yielding insight into the progression of SCC.

PMID- 18329792
TI  - RKIP and BRAF aberrations in human nasal polyps and the adjacent turbinate
      mucosae.
AB  - BACKGROUND: Little is known about the implication of BRAF and RKIP expression, or
      about the incidence of BRAF mutations in the formation of nasal polyposis.
      OBJECTIVES: To determine the expression levels of the genes BRAF and RKIP, and to
      inspect the frequency of BRAF mutations in exons 11, 14 and 15 in human nasal
      polyps (NP). PATIENTS AND METHODS: We analyzed 24 human NP specimens and their
      adjacent inferior and middle turbinates (AIT and AMT), as well as 14 control
      subjects [bearing 14 Control Inferior Turbinates (CIT) and 14 Control Middle
      Turbinates (CMT), in total]. The expression pattern of BRAF and RKIP was assessed
      with real-time RT-PCR. A real-time allele-specific PCR method, in combination
      with direct sequencing, was performed in order to inspect the frequency of the
      V600E mutation in exon 15, and to examine mutation status within exons 11 and 14.
      RESULTS: The control mucosae presented significantly higher mRNA levels for both
      genes, compared to the NP and the AIT-AMT. Moreover, in NP, AIT and AMT, RKIP was
      found to present higher mRNA levels, in relation to the equivalent values of the
      BRAF gene (P=0.003 in NP; P<0.001 both in AIT and AMT). No mutation was detected
      in exon 14, whereas a silent mutation (A1380G, G460G) was noted for one NP sample
      in exon 11. Another NP sample was found to carry two mutations, one T1799A
      (V600E) and one A1801G (K601E). A significant co-expression of the two genes was
      noted in NP (P=0.012) and AIT (P=0.019). CONCLUSION: The results of the
      expression levels of RKIP and BRAF, reflect the strong connection between the two
      genes. RKIP could play an important role in the down-regulation of wild-type
      BRAF, serving thus as an endogenous inhibitor of the MAPK pathway in nasal polyps
      and their adjacent turbinate mucosa.

PMID- 18329793
TI  - TRAIL and cancer therapy.
AB  - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors are
      promising targets for the selective eradication of tumor cells while sparing
      normal cells. Currently, both recombinant TRAIL proteins and TRAIL receptor
      agonistic antibodies are being tested in the clinic, showing encouraging
      antitumor activities and mild side effects. Unfortunately, resistance to TRAIL
      therapy is frequently encountered requiring combined treatments with sensitizing
      agents. Standard chemotherapeutics can enhance TRAIL sensitivity; however, more
      specific and less toxic agents are needed to exploit the full antitumor potential
      of TRAIL. Here, a brief overview of the TRAIL signaling pathway is given together
      with a short description of early results obtained with TRAIL therapy in the
      clinic. Mechanisms of TRAIL resistance and ways to overcome these by targeted
      agents that either neutralize apoptotic blockades or suppress prosurvival signals
      also triggered by TRAIL are highlighted, such as inhibitors of IAPs, Bcl-2 family
      members, HDACi, and modulators of NF-kappaB, Raf and EGFR signaling.

PMID- 18329794
TI  - Determination of Cd, Co, Ni and Pb in biological samples by microcolumn packed
      with black stone (Pierre noire) online coupled with ICP-OES.
AB  - A simple and sensitive method using microcolumn (20-mm length x 2.0-mm i.d.)
      packed with black stone (Pierre noire) for the separation/preconcentration of Cd,
      Co, Ni and Pb in biological samples prior to their online determination by
      inductively coupled plasma optical emission spectrometry (ICP-OES) has been
      developed. Optimal experimental conditions including pH, eluent concentration and
      volume, sample volume and sample flow rate were investigated and established. The
      adsorption capacity of black stone for Cd, Co, Ni and Pb were found to be 23.4,
      21.2, 18.1 and 22.2 mg g(-1), respectively. With a preconcentration time of 72 s
      and an elution time of 4s, an enrichment factor of 20 and a sampling frequency of
      25 h(-1) were obtained. The detection limits corresponding to three times the
      standard deviations of the blank for Cd, Co, Ni and Pb were found to be 0.3, 0.4,
      0.4 and 1.1 ng mL(-1). The precision for seven replicate determinations of Cd,
      Co, Ni and Pb gave relative standard deviations (RSDs) of 5.9, 4.8, 2.7 and 1.1%,
      respectively (n=7, C=10 ng mL(-1)). The method was validated with certified
      reference material GBW09103 human urine and the results obtained were in good
      agreement with the certified values. The method was also applied to the
      determination of the target analytes in biological samples with satisfactory
      results.

PMID- 18329795
TI  - An exposure and risk assessment for fluoride and trace metals in black tea.
AB  - Exposure and associated health risks for fluoride and trace metals in black tea
      were estimated. Fifty participants were randomly recruited to supply samples from
      the tea that they drink, and self-administer a questionnaire that inquired about
      personal characteristics and daily tea intake. Analyzed trace metals included
      aluminum, arsenic, barium, cadmium, cobalt, chromium, copper, manganese, nickel,
      strontium, and zinc. Fluoride and four metals (Al, Cr, Mn, Ni) were detected in
      all samples while barium was detected only in one sample. The remaining metals
      were detected in >60% of the samples. Fluoride and aluminum levels in instant tea
      bag samples were greater than in loose tea samples (p<0.05) while the differences
      in elemental concentrations of loose and pot bag tea samples were not
      significant. Median and 90th percentile daily tea intake rates were estimated as
      0.35 and 1.1l/day, respectively. Neither fluoride nor aluminum levels in black
      tea were found to associate with considerable risks of fluorosis and Alzheimer's
      disease, respectively. However, carcinogenic risk levels for arsenic were high;
      R>1.0 x 10(-6) even at the median level. According to sensitivity analysis, daily
      tea intake was the most influencing variable to the risk except for arsenic for
      which the concentration distribution was of more importance.

PMID- 18329796
TI  - Chemical properties of rare earth elements in typical medical waste incinerator
      ashes in China.
AB  - Medical waste (MW) ashes from different types of MW incinerators were examined to
      detect the characteristics and environmental impact of rare earth elements
      (REEs). The results showed that total REE contents in the ash samples ranged from
      10.2 to 78.9 mg/kg. REEs in bottom ash were apparently higher than those in fly
      ash. Average REE contents in the ashes followed the sequence of
      Ce>La>Nd>Y>Gd>Pr>Sm>Dy>Er>Yb>Ho>Eu>Tb>Lu>Tm. Some of the elements, such as Sm,
      Dy, Ho, Er, Yb in the ash samples were in normal or nearly normal distribution,
      but Y, La, Ce, Pr, Nd, Eu, Gd, Tb, Tm, Lu were not normally distributed,
      indicating some of the ash samples were enriched with these elements. Crust
      normalized REE patterns indicated that two types of the MW ashes were obviously
      enriched with Gd and La. Sequential extraction results showed that REEs in the
      ash mainly presented as residual fraction, while exchangeable and carbonate
      fractions were relatively low. DTPA- and EDTA-extraction tests indicated that
      REEs in the MW ashes were generally in low bioavailability.

PMID- 18329797
TI  - Electrochemical degradation of an anionic surfactant on boron-doped diamond
      anodes.
AB  - In this work, the electrochemical oxidation on boron-doped diamond of synthetic
      wastes polluted with surfactant sodium dodecylbenzenesulfonate (SDBS) has been
      studied. Results show that SDBS can be successfully removed with this technology
      inside different current densities and concentration ranges. The oxidation of the
      SDBS seems to occur in two main sequential steps: the first is the rapid
      degradation of SDBS, and the final is the less efficient oxidation of aliphatic
      intermediates to carbon dioxide. The nature of supporting electrolyte (NaCl,
      Na(2)SO(4) and K(3)PO(4)) influences on the efficiency of the electrochemical
      oxidation process. The treatment of the NaCl solution seems to be more efficient
      in the chemical oxygen demand (COD) removal, while the sulphate and specially the
      phosphate media improve the TOC removal. However, in spite of this observation,
      chemical oxidation of SDBS by different types of oxidants cannot explain alone
      the results of the electrochemical oxidation with diamond anodes. This suggests
      that the synergistic effect of the different oxidation mechanisms that occurs
      into the electrochemical cell (direct oxidation and mediated oxidation by
      hydroxyl radicals and by oxidants formed from the electrolyte) is the responsible
      of the great efficiencies obtained with this technology in the treatment of
      organics.

PMID- 18329798
TI  - Investigation of the possibility of copper recovery from the flotation tailings
      by acid leaching.
AB  - The flotation tailings pond of the Bor Copper Mine poses a great ecological
      problem not only for the town of Bor but also for the surrounding soils and
      watercourses. Since the old flotation tailings contain about 0.2% of copper on
      the average, we investigated their leaching with sulphuric acid in the absence
      and presence of an oxidant. The aim was to determine the leaching kinetics of
      copper and iron as affected by various factors such as: the pH value of the leach
      solution, stirring speed, pulp density, particle size, concentration of ferric
      ions, temperature and time for leaching. The average copper and iron recovery
      obtained was from 60% to 70% and from 2% to 3%, respectively. These results
      indicate that the old flotation tailings pond represents an important source of
      secondary raw material for the extraction of copper and that it should be
      valorized rather than land reclamation. At the end of the paper, a mechanism of
      dissolution of copper and iron minerals from the tailings was described.

PMID- 18329799
TI  - Mechanisms of heavy metal sorption on alkaline clays from Tundulu in Malawi as
      determined by EXAFS.
AB  - Chromium(III), copper(II), zinc(II), cadmium(II), mercury(II) and lead(II)
      cations are among the most common heavy metal pollutants in industrial waste
      waters. In our continued work on cost effective wastewater heavy metal removal
      agents and methods using local material, this study examines the interactions of
      chromium(III), copper(II), zinc(II), cadmium(II), mercury(II) and lead(II)
      cations with natural mixed clay minerals from Tundulu in Malawi using extended X
      ray absorption fine structure (EXAFS) spectroscopy. The mixed clays were
      previously characterised and found to contain illite, low ordered kaolinite,
      mixed layer minerals and the non-clay mineral carbonate fluoroapatite with a mean
      pH(PZC) of 9.63. The EXAFS analyses provided qualitative evidence that oxygen
      atoms occupy the first coordination shells in all the studied central atoms. The
      metal species on the clay mineral surfaces seem to be adsorbates and/or
      precipitates of hydrolysis products. Chromium(III) forms a polynuclear hydrolysis
      complex on the mineral surface with Cr-O bond and Cr...Cr distances of 2.00 and
      3.03 A, respectively, which is indicative of a chain structure with edge sharing
      CrO(6) octahedra. Copper(II) is bound to phosphate groups on the surface at low
      pH and has a first shell of coordinated oxygen atoms with Jahn-Teller distortion
      as revealed by different Cu-O bonds of 1.96 A for the equatorial ones, at 2.30
      and 2.65 A for the axial oxygens, and a Cu-P distance at 3.29 A is distinguished
      as well. Upon treatment at neutral pH copper(I) oxide seems to be the main
      precipitation product on the clay surface. At neutral pH zinc(II) forms also
      polynuclear hydrolysis complexes with Zn-O bond and Zn...Zn distances of 2.01 and
      3.11A, respectively, which shows the presence of edge sharing ZnO(4) tetrahedra.
      Cadmium(II) is adsorbed to the clay surfaces as a six-coordinated CdO(6) complex
      in octahedral fashion, but it is not possible to distinguish if cadmium is
      hydrated or partly hydrolysed. Mercury(II) is present as linear O-Hg-O units but
      without any observable Hg...Hg distance at high pH showing that mercury(II) is
      hydrolysed but not present as mercury(II) oxide. At low pH, linear O-Hg-Hg-O
      units are present showing that mercury(II) is reduced to mercury(I). No precise
      chemical environment around the lead(II) could be obtained for the lead(II)
      treated clays due to formation of different hydrolysis structures with multiple
      coordination numbers by lead(II) salts on the mixed clays.

PMID- 18329800
TI  - Biodegradation of Direct Red 5B, a textile dye by newly isolated Comamonas sp.
      UVS.
AB  - Soil samples collected from the vicinity of "Manpasand textile industry", located
      near Ichalkaranji, India were studied for screening and isolation of bacterial
      strains capable of degradation of textile dyes. A potential strain was selected
      on the basis of rapid dye degradation and later identified as Comamonas sp. UVS.
      Comamonas sp. UVS showed 100% decolorization of Direct Red 5B (DR5B) dye at 40
      degrees C and pH 6.5. The maximum Direct Red 5B concentration decolorized was
      1,100 mg/l in nutrient broth within 125 h. A numerical simulation with the
      Michaelis-Menten kinetics model gives an optimal value of 16.01+/-0.36 mg dye/g
      cell/h for maximum rate (V(max)) and 7.97+/-0.21 mg/l for the Michaelis constant
      (K(m)). The induction in the activities of laccase and LiP was observed during
      decolorization. These enzymes were inhibited by the addition of sodium azide. The
      biodegradation was monitored by UV-vis, FTIR spectroscopy and HPLC. The GCMS
      analysis indicated the presence of 7-benzoylamino-3-diazenyl-4-hydroxy
      naphthalene-2-sulfonic acid in degraded product of the dye. The germination of
      Triticum aestivum seeds was inhibited with DR5B treatment but not with the
      treatment of dye degradation products.

PMID- 18329801
TI  - Potential-pH diagram for "Leucobacter sp. Ch-1-Cr-H(2)O" system.
AB  - Laboratory experiments were used to investigate the effects of initial pH and
      applied potential on the growth of Leucobacter sp. Ch-1 and Cr (VI) reduction and
      establish the pH-Eh diagram for Leucobacter sp. Ch-1-Cr-H(2)O system. The results
      showed that the preferred initial pH for Leucobacter sp. Ch-1 growth was from 7.0
      to 11.0. At this pH range, 56.2-99.5% of Cr (VI) was reduced by Ch-1 strain. The
      applied potentials from -700 to 0 mV, from -800 to +300 mV and from -800 to +400
      mV at 7.0, 9.0 and 11.0 of initial pH values were favorable for the bacterial
      growth. The corresponding ranges of applied potentials for bio-reduction of Cr
      (VI) were from -200 to 0 mV, from -800 to +200 mV, and from -700 to +100 mV at
      above initial pH values. In the potential-pH diagram, the region of initial pH
      and Eh for Cr (VI) bio-reduction was included in the region for Leucobacter sp.
      Ch-1 growth and the stable region of Cr(OH)(3), which implied that Cr (VI) could
      be reduced to trivalent chromium existing in the forms of Cr(OH)(3) precipitate
      under the presence of Leucobacter sp. Ch-1 in alkaline condition. The results
      suggest that Leucobacter sp. Ch-1 has potential application for remediation of Cr
      (VI) contamination sites.

PMID- 18329802
TI  - The relationship between automation complexity and operator error.
AB  - One of the objectives of process automation is to improve the safety of plant
      operations. Manual operation, it is often argued, provides too many opportunities
      for operator error. By this argument, process automation should decrease the risk
      of accidents caused by operator error. However, some accident theorists have
      argued that while automation may eliminate some types of operator error, it may
      create new varieties of error. In this paper we present six case studies of
      explosions involving operator error in an automated process facility. Taken
      together, these accidents resulted in six fatalities, 30 injuries and hundreds of
      millions of dollars in property damage. The case studies are divided into two
      categories: low and high automation complexity (three case studies each). The
      nature of the operator error was dependent on the level of automation complexity.
      For each case study, we also consider the contribution of the existing
      engineering controls such as safety instrumented systems (SIS) or safety critical
      devices (SCD) and explore why they were insufficient to prevent, or mitigate, the
      severity of the explosion.

PMID- 18329803
TI  - Interstitial cells of Cajal associated with the submucosal plexus of the Guinea
      pig stomach.
AB  - Interstitial cells of Cajal (ICC) form specialized networks in the
      gastrointestinal tract that coordinate cellular communications between nerves and
      smooth muscle cells. However, little is known about ICC in the gut mucosa or
      submucosa. Here, we report for the first time that Kit-immunoreactive ICC are
      associated with the submucosal (Meissner's) plexus of the Guinea-pig stomach. In
      longitudinal sections along the greater curvature of the gastric corpus, short
      spindle-shaped ICC of the submucosal plexus (ICC-SP) were located around the
      PGP9.5-immunoreactive nerve elements in the submucosa. Observations of whole
      mount preparations clearly demonstrated Kit-immunoreactive bipolar or multipolar
      cells with long cytoplasmic processes about 100 microm in length. Such cells had
      typical characteristics of ICC, confirming that they were not mast cells, which
      are also Kit-immunoreactive residents of the submucosal connective tissue space.
      Although some ICC-SP surrounded parts of the submucosal plexus, they did not
      appear to form wide extensions of the cellular network, suggesting that they
      acted locally. The demonstration of ICC-SP in the submucosal connective tissue
      space suggests that they may contribute to the regulation of secretion,
      absorption and transportation of fluids in the mucosa.

PMID- 18329804
TI  - Isolation of specific peptides that home to dorsal root ganglion neurons in mice.
AB  - We isolated peptides that home to mouse dorsal root ganglion (DRG) from a phage
      library expressing random 7-mer peptides fused to a minor coat protein (pIII) of
      the M13 phage. An in vitro biopanning procedure yielded 113 phage plaques after
      five cycles of enrichment by incubation with isolated DRG neurons and two cycles
      of subtraction by exposure to irrelevant cell lines. Analyses of the sequences of
      this collection identified three peptide clones that occurred repeatedly during
      the biopanning procedure. Phage-antibody staining revealed that the three
      peptides bound to DRG neurons of different sizes. To determine if the peptides
      would recognize neuronal cells in vivo, we injected individual GST-peptide-fusion
      proteins into the subarachnoid space of mice and observed the appearance of
      immunoreactive GST in the cytosol of DRG neurons with a similar size distribution
      as that observed in vitro, indicating that the GST-peptide-fusion proteins were
      recognized and taken up by different DRG neurons in vivo. The identification of
      homing peptide sequences provides a powerful tool for future studies on DRG
      neuronal function in vitro and in vivo, and opens up the possibility of neuron
      specific drug and gene delivery in the treatment of diseases affecting DRG
      neurons.

PMID- 18329805
TI  - Homeostatic recovery of downstate-upstate cycling in nucleus accumbens neurons.
AB  - Homeostatic plasticity is a powerful cellular mechanism through which neurons
      adjust intracellular and intercellular resources to stabilize their functional
      output through the ever-changing environment. Here, we report a novel form of
      homeostatic plasticity that nucleus accumbens (NAc) neurons use to regain their
      functionally active state once it is lost. In vivo, NAc neurons periodically
      alternate between a functionally active upstate and a functionally quiescent
      downstate. The upstate of NAc neurons is immediately lost following severe
      environmental changes, such as deep anesthesia and truncation of excitatory
      synaptic inputs. Using short-term slice cultures, our current study demonstrates
      that NAc neurons initially lose but gradually recover their upstate-downstate
      cycling after shifting to the in vitro condition. Furthermore, we show that this
      homeostatic recovery of the upstate is mediated by increased synchronization of
      presynaptic activity. Given that being in the upstate is required for in vivo NAc
      neurons to fire action potentials, the homeostatic recovery of upstate may
      underlie an important cellular mechanism for NAc neurons to maintain their
      functional output against severe environmental fluctuations.

PMID- 18329806
TI  - Subunit-specific potentiation of recombinant glycine receptors by NV-31, a
      bilobalide-derived compound.
AB  - Bilobalide, a major bioactive component of Ginkgo biloba herbal extracts,
      exhibits neuroprotective and anti-ischaemic activity. However, its therapeutic
      potential is limited because of its instability. Attempts to synthesise a more
      stable analogue culminated in the development of NV-31. This compound
      recapitulates some aspects of bilobalide pharmacology. However, although
      bilobalide inhibits recombinant glycine receptor Cl channels (GlyRs), NV-31
      potentiates hippocampal neuron GlyRs. Because of the possible therapeutic
      relevance of this effect, the present study investigated the molecular mechanism
      and subunit specificity of NV-31 actions at recombinantly expressed alpha1,
      alpha1beta, alpha2 and alpha3 GlyRs. NV-31 potentiated alpha1 GlyRs by
      approximately 135% with an EC50 near 170 nM. Its potentiating effect was observed
      only at low (EC10) glycine concentrations. The magnitude of its potentiating
      effect was reduced at alpha1beta GlyRs and it had no effect at all at alpha2 and
      alpha3 GlyRs. NV-31 was unlikely to bind at the bilobalide pore-binding site as
      its efficacy was not affected by the alpha1 subunit G2'A and T6'S mutations.
      However, the S15'C mutation to the alcohol-binding site abolished its effects,
      suggesting that NV-31 modulates the GlyR via a specific (steric or allosteric)
      interaction with S15'. GlyRs are potential therapeutic targets for chronic anti
      inflammatory pain and movement disorders. NV-31, as a positive modulator of these
      receptors, thus remains viable as a therapeutic candidate for these disorders.

PMID- 18329807
TI  - Stimulus ambiguity elicits response conflict.
AB  - Conflict monitoring theory [M.M. Botvinick, T. Braver, D. Barch, C. Carter, J.D.
      Cohen, Conflict monitoring and cognitive control, Psychol. Rev. 108 (2001) 625
      652] assumes that perceptual ambiguity among choice stimuli elicits response
      conflict in choice reaction. It hence predicts that response conflict is also
      involved in elementary variants of choice reaction time (RT) tasks, i.e., those
      variants that, by contrast with the Stroop task or the Go/No-Go task for
      instance, are rarely associated with cognitive control. In order to test this
      prediction, an experiment was designed in which participants performed a simple
      RT task and a regular between-hand 2-choice RT task under three different levels
      of stimulus ambiguity. The data show that response conflict, as measured by the
      N2 component of the event-related brain potential (ERP), was elicited in the 2
      choice RT task but not in the simple RT task and that the degree of response
      conflict in the 2-choice RT task was a function of stimulus ambiguity. These
      results show that response conflict is also present in a regular choice RT task
      which is traditionally not considered to be a measure of cognitive conflict.

PMID- 18329808
TI  - Carnosic acid protects neuronal HT22 Cells through activation of the antioxidant
      responsive element in free carboxylic acid- and catechol hydroxyl moieties
      dependent manners.
AB  - In a previous study, we found that carnosic acid (CA) protected cortical neurons
      by activating the Keap1/Nrf2 pathway, which activation was initiated by S
      alkylation of the critical cysteine thiol of the Keap1 protein by the
      "electrophilic"quinone-type of CA [T. Satoh, K. Kosaka, K. Itoh, A. Kobayashi, M.
      Yamamoto, Y. Shimojo, C. Kitajima, J. Cui, J. Kamins, S. Okamoto, T. Shirasawa,
      S.A. Lipton, Carnosic acid, a catechol-type electrophilic compound, protects
      neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway
      via S-alkylation of targeted cysteines on Keap1. J Neurochem., in press]. In the
      present study, we used HT22 cells, a neuronal cell line, to test CA derivatives
      that might be more suitable for in vivo use, as an electrophile like CA might
      react with other molecules prior to reaching its intended target. CA and carnosol
      protected the HT22 cells against oxidative glutamate toxicity. CA activated the
      transcriptional antioxidant-responsive element of phase-2 genes including
      hemeoxygenase-1, NADPH-dependent quinone oxidoreductase, and gamma-glutamyl
      cysteine ligase, all of which provide neuroprotection by regulating cellular
      redox. This finding was confirmed by the result that CA significantly increased
      the level of glutathione. We synthesized a series of its analogues in which CA
      was esterified at its catechol hydroxyl moieties to prevent the oxidation from
      the catechol to quinone form or esterified at those moieties and its carbonic
      acid to stop the conversion from CA to carnosol. In both cases, the conversion
      and oxidation cannot occur until the alkyl groups are removed by an intracellular
      esterase. Thus, the most potent active form as the activator of the Keap1/Nrf2
      pathway, the quinone-type CA, will be produced inside the cells. However, neither
      chemical modulation potentiated the neuroprotective effects, possibly because of
      increased lipophilicity. These results suggest that the neuroprotective effects
      of CA critically require both free carboxylic acid and catechol hydroxyl
      moieties. Thus, the hydrophilicity of CA might be a critical feature for its
      neuroprotective effects.

PMID- 18329809
TI  - Does suckling offer protection to the lamb against Teladorsagia circumcincta
      infection?
AB  - This study tested the hypothesis that milk has a direct effect on the
      establishment of infection with Teladorsagia circumcincta, and provides
      information on the effects of suckling on resilience to infection in young lambs.
      Of 46 six-week-old twin-born lambs, one from each twin was allowed to continue
      suckling (S-) and its twin-weaned (W-) while both were concurrently infected with
      an average of either 0 (-0; n=7/group), 250 (-250; n=8/group) or 1000 (-1000;
      n=8/group) third stage infective larvae (L3) of T. circumcincta per day,
      providing six treatment groups. All groups grazed minimally contaminated pasture,
      and after 42 days were slaughtered for necropsy. Low pasture larval contamination
      was confirmed in W0 and S0 lambs by faecal egg counts (FEC) of less than 30 eggs
      per gram (EPG) and burdens of less than 140 worms. There was no difference in FEC
      between weaned and suckled lambs. Within infection regime, total worm burdens
      were 55-60% greater in the weaned compared with their suckled counterparts
      (P=0.05), and represented 27 and 17%, respectively, net establishment of larvae.
      The greater worm burdens of both groups of weaned animals, which compared with
      their suckled counterparts, and of those infected with 1000 compared with 250
      larvae per day, were associated with shorter female adults that had fewer eggs in
      utero, perhaps indicating intra-worm population regulation, but highlighting the
      limitation of FEC in assessing nematode burdens of such young lambs. There was no
      effect of infection on live weight gain of either weaned or suckled groups and
      the possibility was raised that, in such young lambs, immune unresponsiveness may
      be responsible. The major benefit of continued milk consumption appears to lie
      more in providing nutrients for enhanced growth rather than in improving
      resilience of the lambs to infection.

PMID- 18329810
TI  - Detection of bovine babesiosis in Mozambique by a novel seminested hot-start PCR
      method.
AB  - Babesiosis is a tick borne disease (TBD) caused by parasites of the genus
      Babesia, with considerable worldwide economic, medical, and veterinary impact.
      Bovine babesiosis and other TBDs were considered responsible for 50% of the
      deaths of cattle that occurred in Mozambique in the first year after importation
      from neighbouring countries. Here, we present the detection of Babesia bigemina
      and Babesia bovis in cattle from Mozambique using two distinct PCR methods. For
      this study, blood samples were collected in one farm located near Maputo city.
      The DNA samples were analyzed using a previously described nested PCR and a novel
      hot-start PCR method. Primers were selected for the hot-start PCR based on the
      putative gene of an undescribed aspartic protease named babesipsin, present in
      both B. bovis and B. bigemina. The combination of hot-start polymerase and long
      primers (29-31 bp) were in this study determinant for the successful
      amplification and detection in only one PCR. With a seminested approach the
      sensitivity was further increased. The babesipsin seminested hot-start PCR was in
      this study more sensitive than the nested PCR. A total of 117 field samples were
      tested by seminested hot-start PCR, and 104 were positive for B. bigemina (90%),
      97 were positive for B. bovis (82%), 86 were mixed infections (52%) and only 2
      were negative for both Babesia species (1.7%). The results confirm that this area
      of Mozambique is endemic for babesiosis, and that this TBD should be regarded as
      a threat for imported cattle.

PMID- 18329811
TI  - Qualitative and quantitative evaluation of coprological and serological
      techniques for the diagnosis of fasciolosis in cattle.
AB  - The objectives of this study were (1) to evaluate available coprological and
      serological tests for detection of Fasciola hepatica infection in field
      conditions, (2) to investigate if the season when samples were collected affects
      the interpretation of the test results, and (3) to evaluate if the test results
      are associated with the level of infection. During weekly visits to an abattoir,
      the whole liver, a rectal faecal sample and a blood sample were collected from
      100 cows in two seasons each ("spring"=February-May 2006 and "autumn"=October
      December 2006). A sedimentation-flotation technique on 4g (SF 4g) or 10g (SF 10g)
      of faeces, a copro-antigen ELISA and two indirect serum F. hepatica ELISAs
      (excretory-secretory (ES) and Pourquier ELISA) were performed and the test
      results were compared with the presence of infection and worm counts at liver
      necropsy. Over both seasons the sensitivity (Se) and specificity (Sp) were for
      the SF 4g 43% and 100%, for the SF 10g 64% and 93%, for the copro-antigen ELISA
      94% and 93%, for the ES ELISA 87% and 90% and for the Pourquier ELISA 88% and
      84%. Significant between-season differences (P<0.05) were observed in the
      sensitivities of the two serological ELISAs: whereas the Pourquier ELISA had a
      higher sensitivity in spring than in autumn, the opposite was true for the ES
      ELISA. There were no significant between-season differences in the specificity
      for any of the tests. The test results of the SF 4g, copro-antigen ELISA and ES
      ELISA were associated with the level of infection of the animal. Given a positive
      test result of the SF 4g it is at least 11 times more likely that the animal is
      carrying a heavy infection (>10 flukes) than that is free of infection or lightly
      infected (< or = 10 flukes). Weak ( approximately 0.3) and moderate (
      approximately 0.6) correlations were observed within infected animals of level of
      infection with ES and copro-antigen ELISA results, respectively.

PMID- 18329812
TI  - Corticotropin-releasing hormone receptor 1 coexists with endothelin-1 and
      modulates its mRNA expression and release in rat paraventricular nucleus during
      hypoxia.
AB  - To determine whether corticotropin-releasing hormone receptor 1 (CRHR1) coexists
      with endothelin-1 (ET-1) in rat paraventricular nucleus (PVN), ET-1 expression
      and its regulation by CRH and CRHR1 under hypoxia, rats were exposed to simulated
      continuous hypoxia at 5 km altitude (CH5km, equal to 10.8% O(2)) in a hypobaric
      chamber for 1, 2, 5, 10, 15 or 25 days. ET-1, CRH, and its mRNA were measured
      using radioimmunoassay (RIA), immunohistochemistry, and in situ hybridization.
      The coexistence of ET-1 and CRHR1 was identified by confocal immunofluorescence.
      The results showed that CH5km caused a significant decrease of ET-1 level in PVN
      at 5 days, but decreased CRH on days 1 and 2 while it increased on days 5 and 10.
      CH5km induced ET-1 mRNA upregulation and ET-1 decrease at 5 days, the effects
      were completely reversed by treatment with five-daily-injections of a CRHR1
      antagonist (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]
      pyrimidin-4-yl]-ethylamine: CP-154,526). Also, this treatment significantly
      reversed the CH5km-induced increase in CRH and CRHmRNA in PVN at 5 days. Moreover
      we found that the changes in expression of ET-1 and CRHR1 induced by CH5km were
      co-localized in parvocellular PVN cells. In conclusion, CRHR1 coexists with ET-1
      in parvocellular PVN, continuous hypoxia stimulates ET-1 and ET-1mRNA as well as
      CRH and CRHmRNA, and CRHR1 evidently modulates ET-1 release and ET-1mRNA
      activation caused by continuous hypoxia.

PMID- 18329813
TI  - Deficiency of neural cell adhesion molecule or its polysialylation modulates
      pharmacological effects of the AMPA receptor antagonist NBQX.
AB  - The neural cell adhesion molecule NCAM and its dynamically regulated
      posttranslational modification polysialic acid (PSA) are major determinants of
      cellular interactions during ontogeny. While NCAM in the absence of PSA
      stabilizes cell-cell interactions, the attachment of the large and polyanionic
      PSA negatively influences cell adhesion and promotes plasticity. Disease
      associated changes in the polysialylation state of NCAM raise the question
      whether the PSA-NCAM system can affect CNS pharmacology. Here we investigated the
      pharmacological effects of the competitive AMPA antagonist NBQX in genetic mouse
      models either lacking NCAM and PSA (female NCAM knockout mice) or being
      drastically reduced in the level of PSA expression (female ST8SiaIV knockout
      mice). Studies were carried out with the respective wildtype littermate controls.
      In mice lacking NCAM and PSA, NBQX-induced ataxia proved to be more intense as
      compared with wild-type mice. On both mutant backgrounds, NBQX significantly
      elevated seizure thresholds during i.v. infusion of the chemoconvulsant
      pentylenetetrazole. In summary, the data demonstrate that the PSA-NCAM system
      impacts AMPA receptor pharmacology under in vivo conditions. The fact that
      comparable effects were observed in NCAM- and ST8SiaIV-knockout mice indicates
      that this impact is not due to a stabilizing effect of NCAM in the absence of
      PSA. Thus, disease-related changes in the polysialylation of NCAM are likely to
      be associated with effects on the efficacy and tolerability of AMPA receptor
      antagonists.

PMID- 18329814
TI  - Response to neonatal anesthesia: effect of sex on anatomical and behavioral
      outcome.
AB  - Numerous studies have documented the consequences of exposure to anesthesia in
      models of term and post-term infants, evaluating the incidence of cell loss,
      physiological alterations and cognitive dysfunction. However, surprisingly few
      studies have investigated the effect of anesthetic exposure on outcomes in
      newborn rodents, the developmental equivalent of premature human infants. This is
      critical given that one out of every eight babies born in the United States is
      premature, with an increased prevalence of surgical procedures required in these
      individuals. Also, no studies have investigated if the genetic sex of the
      individual influences the response to neonatal anesthesia. Using the newborn rat
      as the developmental equivalent of the premature human, we documented the effect
      of a single bout of exposure to either the inhalant isoflurane or the injectable
      barbiturate phenobarbital on hippocampal anatomy, hippocampal dependent
      behavioral performance and normal developmental endpoints in male and female
      rats. While both forms of anesthesia led to significant decrements in cognitive
      abilities, along with a significant reduction in volume and neuron number in the
      hippocampus in adulthood, the decrements were significantly greater in males than
      in females. Interestingly, the deleterious effects of anesthesia were manifest on
      developmental measures including surface righting and forelimb grasp, but were
      not evident on basic physiological parameters including body weight or suckling.
      These findings point to the hazardous effects of exposure to anesthesia on the
      developing CNS and the particular sensitivity of males to deficits.

PMID- 18329815
TI  - Roles of peripheral mitogen-activated protein kinases in melittin-induced
      nociception and hyperalgesia.
AB  - Recently, we have reported that melittin, a major toxic peptide of the whole bee
      venom, plays a central role in production of local inflammation, nociception and
      hyperalgesia following the experimental honeybee's sting. However, the exact
      peripheral mechanisms underlying melittin-induced multiple pain-related behaviors
      are still less characterized. In the present study, we sought to investigate the
      potential roles of peripheral mitogen-activated protein kinases (MAPKs) in
      melittin-induced nociception and hyperalgesia by pre- and post-administration of
      three MAPK inhibitors, namely U0126 (1 mug, 10 mug) for extracellular signal
      regulated kinase (ERK), SP600125 (10 mug, 100 mug) for c-Jun N-terminal kinase
      (JNK) and SB239063 (10 mug, 100 mug) for p38 MAPK, into the local inflamed area
      of one hind paw of rats. Both pre- and post-treatment with three drugs
      significantly suppressed the occurrence and maintenance of melittin-evoked
      persistent spontaneous nociception (PSN) and primary heat hyperalgesia, with
      little antinociceptive effect on mechanical hyperalgesia. In vehicle-treated
      group, ipsilateral injection of melittin produced no impact on thermal and
      mechanical sensitivity of the other hind paw, suggesting no occurrence of
      contralateral heat and mechanical hyperalgesia in the melittin test. In addition,
      local administration of each inhibitor into the contralateral hind paw exerted no
      significant influence on either PSN or heat/mechanical hyperalgesia tested in the
      primary injured hind paw, excluding the systemically pharmacological effects of
      the three drugs. Furthermore, local administration of the three compounds in
      naive animals, respectively, did not change the basal pain sensitivity to either
      thermal or mechanical stimuli, suggesting lack of peripherally functional roles
      of the three MAPK subfamily members in normal pain sensitivity under the
      physiological state. Taken together, we conclude that activation of peripheral
      MAPKs, including ERK, JNK and p38, might contribute to the induction and
      maintenance of persistent ongoing pain and primary heat hyperalgesia in the
      melittin test. However, they are not likely to be involved in the processing of
      melittin-induced primary mechanical hyperalgesia, implicating a mechanistic
      separation between mechanical and thermal hyperalgesia in the periphery.

PMID- 18329816
TI  - Different types of nutritional deficiencies affect different domains of spatial
      memory function checked in a radial arm maze.
AB  - Several studies using animal models have suggested that the effects of
      nutritional insult on the developing brain are long-lasting and lead to permanent
      deficits in learning and behavior. Malnutrition can refer to the availability of
      all the nutrients but in insufficient quantities or it may imply that one or more
      of essential nutrients is either missing or is present, but in the wrong
      proportions in the diet. The hypothesis addressed in this study is that different
      domains of cognitive functioning can be affected by malnutrition and this can be
      related to the type of nutritional deficiency that the brain has been exposed to
      during development. To study the effect of nutritional deprivation during brain
      development, a paradigm of maternal malnutrition during the period of gestation
      and lactation was used and its effects were studied on the F1 offspring using
      Swiss albino mice. Three different types of malnutrition were used, that involve,
      caloric restriction, inadequate amount of protein in the diet and condition of
      low iron content. Our results show that the domain of spatial memory affected in
      the F1 generation depended on the kind of malnutrition that the mother was
      subjected to. Further our study shows that although hippocampal volume was
      reduced in all F1 pups, hippocampal subregions of the F1 animals were
      differentially vulnerable depending on type of malnutrition that the mother was
      subjected to. These results highlight the importance of qualifying the kind of
      malnutrition that is suffered by the mother during the period of gestation and
      lactation as it has consequences for the cognitive domain affected in the
      offspring. Awareness of this should inform prevention strategies in trying to
      reverse the effects of adverse maternal nutrition during critical periods in
      brain development.

PMID- 18329817
TI  - Gender-related urocortin 1 and brain-derived neurotrophic factor expression in
      the adult human midbrain of suicide victims with major depression.
AB  - In postmortem brains of patients with major depression, the expression of
      corticotrophin-releasing factor (CRF) is enhanced and that of brain-derived
      neurotrophic factor (BDNF) decreased. In mice over-expressing neuronal CRF (an
      animal model for depression) the expression of urocortin 1 (Ucn1) in the non
      preganglionic Edinger-Westphal nucleus (npEW) is strongly down-regulated.
      Therefore, we hypothesized that an altered activity of Ucn1 neurons in the npEW
      would contribute to the pathogenesis of major depression. To test this hypothesis
      we measured Ucn1 mRNA and BDNF mRNA levels in the npEW of seven male and four
      female, drug-free suicide victims with major depression, and compared the data
      with those obtained from 10 male and seven female individuals without
      neurological and psychiatric disorders (controls). We show that compared with
      controls, the Ucn1-mRNA level in npEW neurons is about 9.12 times higher in male
      but unchanged in female suicide victims. Furthermore, BDNF mRNA expression in
      microdissections of npEW was 3.36 times lower in male suicide victims, but 5.27
      times higher in female victims, compared with controls. Our data also show that
      male suicide victims had almost 11.47 times more Ucn1 and 4.26 times less BDNF
      mRNA in the npEW than female suicide victims. We discuss the significance of
      these data for npEW Ucn1 and BDNF, and propose that altered expressions of Ucn1
      and BDNF in the npEW contribute to the pathogenesis of major depression and/or
      suicidality in a gender-specific manner.

PMID- 18329818
TI  - Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and
      decreases REM sleep in young males.
AB  - Ghrelin activates the somatotropic and the hypothalamic-pituitary-adrenal axes,
      being crucially involved in sleep regulation. Simplified, growth hormone
      releasing hormone (GHRH) increases slow-wave sleep and REM sleep in males, whilst
      corticotropin-releasing hormone (CRH) increases wakefulness and decreases REM
      sleep. Ghrelin's role in sleep regulation and particularly its interactions with
      GHRH and CRH are not entirely clear. We aimed to elucidate the interactions
      between ghrelin, GHRH and CRH in sleep regulation and the secretion of cortisol
      and GH. Nocturnal GH and cortisol secretion and polysomnographies were determined
      in 10 healthy males (25.7+/-3.0 years) four times, receiving placebo (A), ghrelin
      (B), ghrelin and GHRH (C), or ghrelin and CRH (D) at 22:00, 23:00, 00:00, and
      01:00h, in this single-blind, randomized, cross-over study. Non-REM sleep was
      significantly (p<0.05) increased in all verum conditions (mean+/-SEM: B: 355.3+/
      7.4; C: 365.4+/-8.1; D: 371.4+/-3.9min) compared to placebo (336.3+/-6.8min). REM
      sleep was decreased (B: 84.3+/-4.2 [p<0.1]; C: 74.2+/-7.0 [p<0.05]; D: 80.4+/
      2.7min [p<0.05]) compared to placebo (100.9+/-8.3). CRH+ghrelin decreased the
      time spent awake and enhanced the sleep efficiency; furthermore, the REM latency
      was decreased compared to the other treatment conditions. CRH enhanced the
      ghrelin-induced cortisol secretion but had no relevant effect on GH secretion. In
      turn, GHRH enhanced the ghrelin-induced GH secretion but had no effect on
      cortisol secretion. In conclusion, ghrelin exhibited distinct sleep effects,
      which tended to be enhanced by both GHRH and CRH. CRH had sleep-improving and REM
      permissive effects when co-administered with ghrelin, being in contrast to the
      effect of CRH alone in previous studies.

PMID- 18329819
TI  - Physiological and psychological stress responses in adults with attention
      deficit/hyperactivity disorder (ADHD).
AB  - According to self-report and unsystematic observational data adult patients with
      attention-deficit/hyperactivity disorder suffer from increased vulnerability to
      daily life stressors. The present study examined psychological and physiological
      stress responses in adult ADHD subjects in comparison to healthy controls under
      laboratory conditions. Thirty-six subjects (18 patients with DSM-IV ADHD
      diagnosis, 18 sex- and age-matched healthy controls) underwent the Trier Social
      Stress Test (TSST; Kirschbaum, C., Pirke, K.-M., Hellhammer, D.H., 1993. The
      "Trier Social Stress Test"--a tool for investigating psychobiological stress
      responses in a laboratory setting. Neuropsychobiology 28, 76-81), a standardized
      psychosocial stress protocol which contains a stress anticipation phase and a
      stress phase with a free speech assignment and subsequent performance of a mental
      arithmetic. Physiological stress measures were salivary cortisol as an indicator
      of the HPA axis, heart rate (HR), and time- and frequency-domain heart rate
      variability (HRV) parameters. Subjective stress experience was measured via self
      report repeatedly throughout the experimental session. In line with previous
      theoretical and empirical work in the field of childhood ADHD, it was
      hypothesized that the ADHD and control group would exhibit comparable baseline
      levels in all dependent variables. For ADHD subjects, we expected attenuated
      responses of the physiological parameters during anticipation and presence of the
      standardized stressor, but elevated subjective stress ratings. Hypotheses were
      confirmed for the baseline condition. Consistent with our assumptions in regard
      to the psychological stress response, the ADHD group experienced significantly
      greater subjective stress. The results for the physiological variables were
      mixed. While ADHD subjects revealed an attenuated HR during the stress phase, no
      significant group differences were found for the other parameters, although a
      trend was observed for both the low frequency/high frequency (LF/HF) ratio of the
      HRV power spectral analysis and salivary cortisol (the latter possibly indicating
      generally lower cortisol levels in ADHD subjects). In summary, the present
      findings are the first to demonstrate a significant alteration of a specific
      physiological stress measure (HR) and, more clearly, of psychological aspects of
      the stress response in adults suffering from ADHD. In regard to the physiological
      stress response, it is recommended that future studies employ larger sample sizes
      and a more comprehensive range of physiological stress parameters. Additionally,
      the issue of transferability of laboratory results to real life stressors needs
      to be addressed.

PMID- 18329820
TI  - Comment on Eskenazi et al.

PMID- 18329821
TI  - Sensations referred to a patient's phantom arm from another subjects intact arm:
      perceptual correlates of mirror neurons.

PMID- 18329822
TI  - A new phenolic glycoside from the aerial parts of Dryopteris fragrans.
AB  - A new phenolic glycoside, 3,5-dimethyl-6-hydroxy-2-methoxy-4-O-D-glucopyranosyl
      oxy-acetophenone (1), was isolated from the aerial parts of Dryopteris fragrans.
      The structure was elucidated on the basis of spectroscopic methods.

PMID- 18329823
TI  - [Aeromonas spp. infections: retrospective study in Nimes University Hospital,
      1997-2004].
AB  - OBJECTIVE: Retrospective study of patients presenting Aeromonas spp. infections
      admitted to Nimes hospital from January 1997 to December 2004. PATIENTS AND
      METHOD: Aeromonas spp. infections were collected from the database of the
      bacteriology department. The Aeromonas species, suceptibility phenotype,
      epidemiological data, site and type (nosocomial or not) of infection, and
      evolution were collected from medical files. RESULTS: Thirty infections were
      notified corresponding to 22 male and eight female of 50.6 years old (mean) and a
      mean stay duration of 31 days. Skin and soft tissues (50%), digestive tract
      (26.7%), bones and articulations (10%), blood stream (6.7%), urinary tract (3.3%)
      and lymph nodes (3.3%) were the sites of infection. Ten infections were
      nosocomial, four were associated with medical leeches. All strains were
      resistants to amoxicillin and amoxicillin- clavulanic acid, whereas resistance
      rate to other beta-lactams was under 10% and all were suceptible to
      fluoroquinolones and aminoglycosides. All patients received antibiotic treatment:
      31% a single molecule, 69% an association and 62% needed a second line treatment.
      Strain was suceptible to the antibiotic in 78.5% of cases. Only one death occured
      not directly linked to Aeromonas infection. DISCUSSION: Most of Aeromonas spp.
      infection sites were cutaneous and digestive. Nosocomial infections associated
      with medical leeches are not so uncommon and strict conditions of storage and
      administration are necessary. According to the susceptibility phenotype of our
      strains which is similar to literature data, a third generation cephalosporin or
      a fluoroquinolone should be used evenly associated with an aminoglycoside.

PMID- 18329824
TI  - Detectability and criterion measures in temporal generalization.
AB  - Computer simulation of performance on "normal" and "episodic" temporal
      generalization tasks was used to examine the relations between the theoretical
      parameters of models which fit temporal generalization data ("timing sensitivity"
      and "threshold"), and the d' (detectability) and beta (decision criterion)
      measures of signal-detection theory. In general, changes in timing sensitivity
      altered d', whereas threshold changes affected beta, supporting the assertion
      that the two sorts of variables ("sensitivity/detectability" and
      "threshold/criterion") were psychologically equivalent. Cases where temporal
      generalization gradients were apparently contaminated by "random responding"
      could be treated by changes in beta, but cases in which temporal generalization
      gradients were not peaked at the standard posed severe problems for a simple
      signal-detection account, although existing models of temporal generalization
      performance could deal with them.

PMID- 18329825
TI  - Polydrug use and implications for longitudinal research: ten-year trajectories
      for heroin, cocaine, and methamphetamine users.
AB  - A typical approach to categorizing substance users for epidemiologic purposes or
      to identify substance use problems at treatment admission is by indicating the
      primary substance used and/or for which treatment is sought. But does such
      singular focus on the primary drug limit the validity of conclusions from
      longitudinal analysis of drug use patterns over time? This analysis combined data
      from five longitudinal studies conducted in California and examined 10-year
      patterns of heroin, cocaine, methamphetamine (meth), marijuana, and alcohol use
      for primary users of heroin (n=629), cocaine (n=694), and meth (n=474). Results
      suggest relatively low levels of use of non-primary heroin, cocaine, and meth,
      but moderate levels of alcohol and marijuana use. Growth models showed declining
      primary drug levels for heroin and meth users and relatively consistent levels
      over 10 years for cocaine users, while levels of non-primary drugs remained at
      consistently low levels or declined in tandem with the primary drug. Results
      indicate that group descriptions of primary heroin, cocaine, or meth use
      trajectories over time may present valid information about drug use patterns in
      general.

PMID- 18329826
TI  - Gender identity and substance use among students in two high schools in
      Monterrey, Mexico.
AB  - This study explored relationships between several hypothesized dimensions of
      gender identity and substance use outcomes within a non-probability sample of
      adolescents in Monterrey, Mexico. Based on Mexican concepts of machismo and
      marianismo, four gender identity constructs were measured: aggressive
      masculinity, assertive masculinity, affective femininity and submissive
      femininity. The study assessed how well these gender identity measures predicted
      substance use behaviors, substance use intentions, expectancies, and normative
      approval, and exposure and vulnerability to substance offers. Data were drawn
      from questionnaires completed by 327 students from 2 Monterrey secondary schools.
      Multivariate ordered logistic and linear regression analyses, adjusted for school
      level effects, indicated that aggressive masculinity was associated with higher
      risk of drug use on most outcomes, while affective femininity was associated with
      lower risk on selected outcomes. Assertive masculinity was associated with only
      one of the outcomes examined and submissive femininity with none of them. Most
      gender identity effects persisted after controlling for biological sex, academic
      performance, age, and other gender identity measures. For two of the outcomes,
      the gender identity measures had significantly stronger effects for males than
      for females. The findings are interpreted in light of males' higher risk for drug
      use and changes in gender roles and gendered behavior that are now occurring in
      Mexico as in the U.S.

PMID- 18329827
TI  - The therapeutic alliance in medical-based interventions impacts outcome in
      treating alcohol dependence.
AB  - This study examined the relationship of the therapeutic alliance and treatment
      outcomes for alcohol-dependent patients receiving naltrexone or placebo and one
      of three different types of clinical interventions, including two medical-based
      (non-specialty) treatments. This is a secondary analysis of a 24-week randomized,
      placebo-controlled, clinical trial of 100mg/day of naltrexone or placebo for
      patients with DSM-IV alcohol dependence. Patients were also randomized to one of
      three interventions: (1) medication clinic only, (2) medication clinic plus
      BRENDA (an intervention promoting pharmacotherapy), or (3) medication clinic plus
      cognitive behavioral therapy (CBT). Early in treatment, patients and clinicians
      completed the working alliance inventory (WAI). Regression analyses were
      conducted to determine the predictive validity of the WAI on percent days
      abstinent and percent of sessions attended over the clinical trial. In the
      medication clinic only condition, the clinicians' WAI total score was marginally
      correlated to percent of visits attended (p=.057) but not percent days abstinent.
      In the medication clinic plus BRENDA condition, clinicians' WAI total score was
      positively correlated with percent days abstinent (p=.013) but not percent visits
      attended. No significant relationships were found between the WAI scores and
      either outcome measure in the CBT condition or for any of the patient rated
      assessments. To our knowledge, this is the first published report providing some
      support for the importance of the therapeutic alliance in medical interventions
      for alcohol dependence but only in the context of the clinicians' ratings. The
      absence of other effects underscores the need for further research.

PMID- 18329828
TI  - Postnatal growth failure in preterm infants: recovery of growth and body
      composition after term.
AB  - BACKGROUND: Many preterm infants are significantly growth restricted at hospital
      discharge and are at increased risk for long-term growth failure. AIMS: To
      compare growth and weight gain composition after term between preterm infants who
      were growth retarded and those who were not. STUDY DESIGN: An observational
      longitudinal study was conducted. SUBJECTS: 35 preterm infants who showed growth
      retardation at term (group 1) and 26 preterm infants who did not (group 2).
      OUTCOME MEASURES: Growth and body composition were assessed at term and at 1, 2,
      3, 4 and 5 months of corrected age. RESULTS: At term, and at 1, 2, and 3 months
      of corrected age, growth-retarded infants showed significantly lower body weight
      and fat mass than infants who did not develop growth retardation. The mean energy
      and protein intakes did not differ significantly between the two groups. Daily
      increases in body weight and fat mass between term and three months did not
      differ between the groups. However, during the fourth and fifth months, daily
      gains of body weight and fat mass were significantly greater in growth-retarded
      than in non-growth-retarded infants, and as a result, body weight and fat mass
      were comparable between the two groups at 4 and 5 months of corrected age.
      CONCLUSIONS: In terms of growth parameters and body composition, growth-retarded
      preterm infants recovered from postnatal growth failure within the fourth month
      of corrected age.

PMID- 18329829
TI  - Increased stress tolerance of matured pig oocytes after high hydrostatic pressure
      treatment.
AB  - The present paper describes a method which uses high hydrostatic pressure as a
      pre-treatment to in vitro matured porcine oocytes to improve their survival rates
      in the subsequent processes including cryopreservation, parthenogenetic
      activation and embryo culture. In Experiment I oocytes were treated with
      different pressure impulses in the range of 20-80 MPa (200-800 times greater than
      atmospheric pressure) for 30-120 min at 24 degrees C. For parthenogenetic
      activation a single dc of 12.5 kV/cm was used, to test shock tolerance of the
      treated vs. control oocytes and also compare their developmental competence
      evaluated with continued in vitro development. The upper limit of pressure
      tolerance was found in the 40 MPa range. In Experiment II oocytes pre-treated
      with pressures in the 20-40 MPa range were vitrified with the Cryotop method, and
      parthenogenetically activated subsequently with combined electric (single dc of
      1.25 kV/cm) and chemical treatment after warming. According to our investigations
      performed with a total of 1980 oocytes and 3-5 replicates, pressure treatment
      increased cleavage and blastocyst rates after activation and cleavage rates after
      vitrification followed by activation. Our results indicate that the sublethal
      pressure treatment may induce specific responses in oocytes increasing their
      resistance and developmental competence. The mechanism that may lie behind the
      observations is the sublethal stress-induced post-transcriptional activation of
      shock proteins in the oocytes. Further investigations are needed to reveal the
      biophysical and molecular biological background of the findings and to optimize
      the protocol of pressure pre-treatment in both animal- and human-assisted
      reproductive technology (ART) to increase the efficiency of in vitro procedures.

PMID- 18329830
TI  - In vivo antiviral activity of ribavirin/alpha-cyclodextrin complex: evaluation on
      experimental measles virus encephalitis in mice.
AB  - Intracranial injection of the rodent adapted CAM/RB strain of measles virus (MV)
      induces encephalitis in CBA/ca mice. It has already been shown that cyclodextrins
      can be used as carriers to increase the antiviral activity of ribavirin (RBV)
      against MV in cellular model. In this study, the antiviral activity of a
      RBV/alpha-cyclodextrin complex has been evaluated in vivo using the above model.
      CBA/ca mice were treated by intraperitoneal injection of free ribavirin (40
      mg/kg) or a RBV/alpha-cyclodextrin complex (molar ratio 1:3). After 21 days,
      intracerebral injection of CAM/RB resulted in 100% mortality in the mock group.
      In contrast, mortality rates of 80% and 40%, respectively, were observed in RBV
      and RBV/alpha-CD-treated mice (p<0.05 and p=0.06 for distilled water and RBV,
      respectively). The viral load of MV in the mouse brain was monitored daily by
      real-time PCR until day 6 after infection, to compare virus production in treated
      and non-treated mice. This data shows that RBV complexation with alpha
      cyclodextrin can increase the antiviral activity of ribavirin in a measles virus
      encephalitis model in mice.

PMID- 18329831
TI  - Cisplatin induces cytoplasmic to nuclear translocation of nucleotide excision
      repair factors among spiral ganglion neurons.
AB  - Genomic DNA is a high-affinity target for the antineoplastic molecule cisplatin.
      Cell survival from cisplatin DNA damage is dependent on removal of cisplatin-DNA
      adducts by nucleotide excision repair (NER) pathways. The rate-limiting steps in
      the NER pathways are DNA damage identification and verification. These steps are
      accomplished by xeroderma pigmentosum complementation group C and A (XPC and XPA)
      and RNA polymerase II. Unlike RNA polymerase II, XPC and XPA have no known
      cellular function beyond DNA repair. Cisplatin is known to damage spiral ganglion
      neurons at the basal coil of the cochlea therefore it was posited that cisplatin
      may target their DNA and mobilize XPC and XPA. Female Fisher344 rats were given
      two, four day cycles of cisplatin (2mg/kg) or saline, separated by a 10day rest
      period. A 2 x 3 x 2 factorial design, consisting of two treatment conditions
      (cisplatin and saline treatment), three survival times (5, 19 and 22 days) and
      two analysis methods (quantitative RT-PCR and immunohistochemistry) was employed
      to evaluate the expression and distribution of XPC and XPA. Quantitative RT-PCR
      revealed statistically significant differences in cochlear XPC and XPA mRNA
      levels after cisplatin treatment at all times except day 22 for XPA.
      Immunohistochemistry revealed that a proportion ( approximately 50%) of spiral
      ganglion neurons in control rats showed cytoplasmic expression of XPC and XPA.
      After cisplatin treatment, a similar proportion ( approximately 50%) of spiral
      ganglion neurons showed increased nuclear expression of XPC and XPA, which
      appears to represent translocation from the cytoplasm. Basal coil spiral ganglion
      neurons translocated XPC and XPA at later treatment cycles and with less
      magnitude than apical coil neurons after cisplatin treatment. Therefore, it is
      suggested that cisplatin treatment induces nuclear translocation of NER proteins
      among spiral ganglion neurons and that this nuclear translocation is less
      efficient at the base relative to the apex.

PMID- 18329832
TI  - Effects of ginsenoside Rb1 at low doses on histamine, substance P, and monocyte
      chemoattractant protein 1 in the burn wound areas during the process of acute
      burn wound repair.
AB  - AIM OF THE STUDY: We reported recently that the facilitating effects of
      ginsenosid Rb(1) on burn wound-healing might be due to the promotion of
      angiogenesis. Increased histamine, substance P (SP), and monocyte chemoattractant
      protein (MCP)-1 levels caused inflammation, and pain following severe burn wound
      injury. MATERIALS AND METHODS: We examined the effects of ginsenoside Rb1 on the
      histamine, SP, and MCP-1 levels in burn wound tissue during burn wound repair.
      RESULTS AND CONCLUSIONS: Ginsenoside Rb1 (1 ng/wound) and basic fibroblast growth
      factor (bFGF) (2.5 microg/wound) significantly increased the levels of MCP-1 on
      day 1 compared to the MCP-1 level in vehicle-treated mice. Histamine production
      of the burn wound area on day 7 was increased by topical application of
      ginsenoside Rb1 (100 fg-1 ng/wound) and bFGF. The number of mast cells migrating
      to the burn wound area was also increased by ginsenoside Rb1. Conversely, the
      increased SP production was reduced by ginsenoside Rb1. This finding suggests
      that the pain induction by burn injury may be reduced by ginsenoside Rb1. The
      facilitating actions of ginsenoside Rb1 on burn wound healing may be due to the
      increase in histamine production via the increase in mast cell migration to the
      burn wound area induced by the rapid elevation of MCP-1.

PMID- 18329833
TI  - MR spectroscopy of the brain in Leigh syndrome.
AB  - Brain magnetic resonance spectroscopy in two patients with Leigh syndrome
      revealed the presence of lactate in gray and white matter brain tissue and
      relatively high choline levels in the white matter. The latter observation, most
      probably related to an ongoing demyelination process, underlines specific
      involvement of white matter metabolism in Leigh syndrome even in cases without
      involvement of the white matter as visualized on MRI. Magnetic resonance
      spectroscopy might thus be of help in differentiating Leigh syndrome from a range
      of other mitochondrial diseases, such as ophthalmoplegia and Kearns-Sayre
      syndrome, showing lack of lactate in brain tissues appearing normal on MRI.

PMID- 18329834
TI  - Magnetic resonance angiography (MRA) in renally impaired patients: when and how.
AB  - Magnetic resonance angiography (MRA) and NSF in renally impaired patients have a
      close relationship due to the frequent coincidence of vascular and renal
      pathologies, the relatively large amount of contrast media applied and the
      delayed excretion. The date of the first NSF cases described in literature falls
      into the development of multi-stationary MRA--an investigation that requested
      multiple bolus injections or one large bolus of the contrast agent. It is
      therefore easily understood that NSF was regarded initially as possible
      complication of MRA. A review on the history of MRA is presented and various
      techniques for MRA are described. While many neuroradiological indications can be
      solved by native MRA, most angiographic indications throughout the body rely on
      the application of intravenous contrast agents. The paper discusses options for
      alternative methods in vascular imaging and offers guidelines for patients with
      renal impairment. NSF must always be balanced versus the outcome of an
      investigation, respectively versus the outcome of a denied MRA. Moreover, in
      patients with chronic kidney disease (CKD) and a proper justification for a
      vascular investigation, neither CT angiography nor DSA should replace MRA.
      Restrictions in contrast media dose for CKD patients are mandatory and obviously
      reduce the risk of NSF. Gadolinium-based contrast agents with lower stability are
      now contraindicated in patients with reduced renal function. The role of blood
      pool agents is under evaluation. Since the awareness of the new disease grew over
      the last year, radiologists were able to reduce the number of newly diagnosed NSF
      cases by more careful consideration of contrast application and agent in renally
      impaired patients, which gives hope that NSF can be avoided by respecting some
      easy rules.

PMID- 18329835
TI  - Comparative activity of meropenem in US medical centers (2007): initiating the
      2nd decade of MYSTIC program surveillance.
AB  - Since 1997, the Meropenem Yearly Susceptibility Test Information Collection
      (MYSTIC) Program has monitored the antimicrobial activity of broad-spectrum
      agents against pathogens from hospitalized patients. In the United States, 2894
      isolates were submitted in 2007 from 15 sites, including 1392 Enterobacteriaceae,
      643 nonfermentative Gram-negative bacilli, and 829 Gram-positive cocci. All
      isolates were tested by broth microdilution methods. Meropenem (MIC(90) range,
      0.12-2 microg/mL) exhibited the lowest resistance rates (1.9-2.4%) against
      Enterobacteriaceae, and fluoroquinolones had the highest rates of resistance
      (17.3-18.3%). KPC carbapenemases, usually found in Klebsiella pneumoniae, were
      also detected in Citrobacter freundii, Enterobacter spp., and Escherichia coli.
      Confirmed extended-spectrum beta-lactamase-producing isolate rates for E. coli,
      Klebsiella spp., and Proteus mirabilis isolates were 6.0%, 12.0%, and 0.0%,
      respectively. Meropenem remained active against Gram-positive pathogens such as
      staphylococci (methicillin-susceptible; MIC(90), 0.12-0.25 microg/mL),
      Streptococcus pneumoniae (MIC(90), 0.5 microg/mL), and beta-hemolytic and
      viridans group streptococci (MIC(90) range, 0.06-0.25 microg/mL). These US MYSTIC
      Program results demonstrate the continued emergence of novel beta-lactamases and
      multidrug-resistant bacterial phenotypes necessitating monitoring of carbapenem
      activities against Enterobacteriaceae species as well as nonfermentative bacilli.

PMID- 18329836
TI  - An 11-year retrospective study of totally implanted central venous access ports:
      complications and patient satisfaction.
AB  - AIMS: We wanted to assess the factors that predict complications and patient
      satisfaction of totally implanted central venous access ports (TIAP). METHODS: We
      reviewed 550 patients with breast or gynaecological malignancies who had initial
      port placement for chemotherapy between 1995 and 2006. We retrospectively
      assessed all TIAP complications, port duration and follow-up care until the TIAPs
      were removed (or the last known recorded documentation) or until the death of the
      patient. TIAP-related patient satisfaction was also assessed via a questionnaire
      based survey of 356 patients. RESULTS: 561 TIAPs were placed in 550 cancer
      patients (11 patients received 2 TIAPs during the study period); the median time
      of port duration was 22.5 months. There were 104 complications in this group. Of
      these, 81 occurred during chemotherapy treatment that lasted a median time of 182
      days. Removal secondary to complication was observed in 48 cases. TIAPs placed on
      the left chest side, through the subclavian vein or with the catheter tip
      localized in the peripheral part of superior vena cava demonstrated the highest
      incidence of complications. Patients with a BMI >28.75 had an increased risk for
      developing complications. Our follow-up questionnaire revealed a 93% patient
      satisfaction rate with the TIAP. CONCLUSIONS: Patients with left-sided ports,
      catheter tips lying in the upper part of the superior vena cava and implantation
      via the subclavian vein are at a higher risk for TIAP-associated complications.
      Being excessively overweight was assessed as another risk factor for developing
      complications. TIAPs are highly accepted and further recommended by patients.

PMID- 18329837
TI  - [Complication after amygdalectomy in children].

PMID- 18329838
TI  - [The priorities of public health must participate in the regulation of health
      networks].

PMID- 18329839
TI  - [Home accidents associated with anosmia].
AB  - OBJECTIVE: To assess the risk of home accidents related to severe hyposmia.
      METHODS: A questionnaire, completed by 57 hyposmic patients and 49 control
      subjects with a normal sense of smell, asked about four specific types of
      olfactory-related home accidents: undetected fires, undetected gas leaks,
      consumption of spoiled food, and incidents of food burning. Level of olfactory
      function was determined by olfactory testing (Biolfa). RESULTS: Olfactory testing
      revealed that 60% of the patients were anosmic and 40% had severe hyposmia. They
      reported cooking-related accidents most often (63%), followed by eating spoiled
      food (51%), inability to detect a gas leak (47%) and inability to smell a fire
      (26%). All these accidents were significantly more frequent than in the control
      population (p<10(-4)). DISCUSSION AND CONCLUSION: This paper, the first in the
      European literature and the second in the international literature, shows that
      patients with severely impaired olfaction are more likely to experience related
      accidents than those with normal olfactory function.

PMID- 18329840
TI  - In memoriam. William L. "Bill" Marcus, J.D.

PMID- 18329841
TI  - An institutional quality improvement initiative for pain management for pediatric
      cancer inpatients.
AB  - Health care institutions must use the principles of quality improvement to
      demonstrate appropriate assessment and effective management of pain. Here, we
      describe the quality improvement initiative implemented at our pediatric
      institution to improve the quality of pain management. We conducted chart audits
      for the previous 24 hours during which patients received inpatient care. Over six
      years, 2,478 charts were audited for 87 24-hour periods (average 1.2 days/month)
      to answer the following: (1) Was pain intensity assessed as per the institutional
      pain standard of care, (2) What proportion of audited inpatients had significant
      pain (>or=5/10), and (3) When significant pain (>or=5/10) occurred, was treatment
      effective (pain score <or=4/10) within one hour of an intervention? Data were
      analyzed for quarterly time periods (n=24). Compliance with pain assessment
      guidelines improved from 77% initially to consistently greater than 90%. The mean
      proportion of patients with significant pain each quarter was 21%. Sixty-six
      percent of patients with significant pain had pain treated effectively within one
      hour of intervention. Lack of documentation of pain reassessment within one hour
      of the intervention was consistent throughout the study period (overall frequency
      22%). Comprehensive pain management guidelines have been established. Leaders of
      health care organizations need to provide the support and resources needed to
      incorporate these guidelines and standards into institutional culture. We present
      a simple quality improvement approach to patient care that can be modified to fit
      the unique aspects of other institutions.

PMID- 18329842
TI  - Antioxidative potential of melatonin against mercury induced intoxication in
      spermatozoa in vitro.
AB  - Mercury is one of the most investigated natural elements and potential
      contaminants in the environment. Antioxidants have long been known to reduce the
      free radical-induced oxidative damage. Considering the antioxidant properties of
      melatonin, this study was aimed to evaluate the effect of melatonin on
      antioxidant system of rat epididymal sperm in vitro. Sperm samples were dispersed
      in RPS medium (pH 6.9) and incubated with mercury in the form of mercuric
      chloride (MC) at three different concentrations (1 microM, 10 microM, 100
      microM), melatonin (MLT) at a concentration (100 microM) and mercuric
      chloride+melatonin (100 microM each) for 3h at 32 degrees C. Sperm viability and
      motility were assessed every 30 min during the 3-h incubation period. An aliquot
      of sperm sample was homogenised, centrifuged and used for the assay of superoxide
      dismutase, glutathione peroxidase, glutathione reductase, TBARS assay to detect
      lipid peroxidation and hydrogen peroxide generation assay. Samples treated with
      mercury showed a dose-dependent decrease in motility while there was no
      significant decrease in sperm viability. In mercury-incubated sperm, the activity
      of superoxide dismutase, glutathione peroxidase and glutathione reductase
      decreased significantly while TBARS levels and H2O2 generation were increased in
      a dose-dependent manner. Co-incubation of sperm with mercury and melatonin
      exhibited no significant changes in the levels of motility, viability and
      antioxidant indices as compared to untreated controls. The results suggest that
      graded doses of mercury elicit depletion of antioxidant defense system in sperm
      without altering the viability and melatonin treatment was found to significantly
      inhibit oxidative damage caused by mercury.

PMID- 18329843
TI  - Convergent and discriminant validity of the Children's Yale-Brown Obsessive
      Compulsive Scale-Symptom Checklist.
AB  - The Children's Yale-Brown Obsessive Compulsive Scale-Symptom Checklist (CY-BOCS
      SC; Scahill, L., Riddle, M. A., McSwiggin-Hardin, M., Ort, S. I., King, R. A.,
      Goodman, W. K., et al. (1997). Children's Yale-Brown Obsessive Compulsive Scale:
      Reliability and validity. Journal of the American Academy of Child and Adolescent
      Psychiatry, 36, 844-852) is widely used to assess the presence of obsessions and
      compulsions in youth. Although factor analytic studies have established symptom
      dimensions of the CY-BOCS-SC, little is known of its psychometric properties. The
      present study sought to examine the convergent and discriminant validity of the
      CY-BOCS-SC. Eighty-six youth with obsessive compulsive disorder (OCD) and their
      parents were administered the CY-BOCS-SC, the CY-BOCS severity items, and the
      Anxiety Disorders Interview Schedule for DSM-IV: Parent Version (ADIS-IV-P).
      Children completed the Children's Depression Inventory and Multidimensional
      Anxiety Scale for Children. Internal consistency of CY-BOCS-SC symptom dimensions
      ranged from poor to good. The CY-BOCS-SC demonstrated good to excellent
      convergent validity, as demonstrated by large correlations with conceptually
      similar items on the ADIS-IV-P. The discriminant validity of the CY-BOCS-SC was
      also good, as evidenced by small, generally non-significant, correlations between
      the CY-BOCS-SC dimensions and depressive and anxiety symptoms, OCD symptom
      severity, and trichotillomania symptoms. These results provide initial
      psychometric support for the CY-BOCS-SC and support its use as a clinical and
      research instrument for assessing presence of a range of obsessive and compulsive
      symptoms in youth with OCD.

PMID- 18329844
TI  - Chronic thought suppression and posttraumatic symptoms: data from the Madrid
      March 11, 2004 terrorist attack.
AB  - Although a considerable number of people either witnessed directly or in the mass
      media the traumatic scenes of the terrorist attack that took place on March 11th,
      2004 in Madrid, only a fraction of Madrid citizens developed posttraumatic
      symptoms. In this study, posttraumatic stress-related symptoms, degree of
      exposure, coping strategies related to the attack, and chronic attempts to avoid
      intrusive thoughts (i.e., thought suppression) were assessed in a general
      population Madrid sample (N=503) 2-3 weeks after the attacks. Our results showed
      that participants with higher scores in chronic thought suppression exhibited
      higher levels of PTSD symptoms. Higher scores in chronic thought suppression also
      correlated positively with the use of avoidant coping strategies after the
      attacks. We discuss the possible common roots of avoidance of intrusive thoughts
      and avoidant coping strategies and the implications of this relationship for the
      emergence of stress-related symptoms as well as for public health policies.

PMID- 18329845
TI  - Vocal fold paresis: clinical and electrophysiologic features in a tertiary
      laryngology practice.
AB  - A retrospective chart review was performed at the senior author's voice disorder
      clinic to report the symptoms, signs, and laryngeal electromyography (LEMG) data
      of patients presenting with vocal fold paresis (VFP) in a tertiary laryngology
      academic practice over a 4-year period. Medical records of 739 patients
      presenting to the clinic with a chief complaint of dysphonia (for 2000-2004) were
      assessed. History intake forms, strobovideolaryngoscopy images, and LEMG reports
      were reviewed for all patients with a clinical diagnosis of VFP. Of the 739
      patients presenting to the clinic with voice complaints, 195 were initially
      diagnosed with either vocal fold paralysis or VFP (26.4%). Only 13 out of 739
      patients (1.8%) with voice complaints were diagnosed with LEMG-confirmed
      unilateral or bilateral VFP. The most common findings on strobovideolaryngoscopy
      were vocal fold bowing (70%), incomplete closure (62%), and increased vibratory
      amplitude (38%). Seventy percentage of the patients had unilateral VFP,
      predominantly isolated recurrent laryngeal nerve (RLN) disease. Only 9% had
      unilateral superior laryngeal nerve (SLN) involvement. The most common LEMG
      abnormality was reduced recruitment of motor units. In our voice center, VFP was
      a relatively uncommon diagnostic entity. Despite the low prevalence, VFP needs to
      be considered in all patients who present with dysphonia. Further study is needed
      to examine the prevalence of "abnormal" LEMG studies in an asymptomatic control
      population, and to determine the utility of LEMG in the evaluation and management
      of dysphonia. In the same way that strobovideolaryngoscopy has been critically
      evaluated in the past, there is also a need to determine how commonly LEMG
      contributes essential data which leads to a change in the patient's management
      and/or ultimate vocal outcome.

PMID- 18329846
TI  - Derivation of a size-independent variable for scaling of cardiac dimensions in a
      normal adult population.
AB  - OBJECTIVE: Most current methods for normalizing cardiac dimensions for
      differences in body size assume a linear isometric relationship between
      variables. This approach may be flawed. We therefore compared the isometric and
      allometric modeling approach to assess the optimal scaling method (using the left
      atrial dimension [LAD] as an example) in a large group of adults with normal
      echocardiograms. METHODS: We studied 15,667 consecutive echocardiographically
      normal adults. Their mean age was 40 +/- 14 years; LAD was 32 +/- 4 mm; body
      weight (BW) was 72 +/- 17 kg; height (HT) was 1.7 +/- 0.2 m; body surface area
      (BSA) was 1.8 +/- 0.2 m(2); and body mass index was 25 +/- 6 kg/m(2). The LAD in
      the anterior-posterior dimension was indexed by each size variable using both
      isometric and allometric methods. RESULTS: LAD correlated with all size variables
      (r = 0.20 to r = 0.45). Simple isometric indices (e.g., LAD/BSA), rather than
      removing, actually increased the correlation with all body size variables (r = 
      0.27 to -0.80). Normalization by the optimal allometric exponent (BW = 0.262; HT
      = 0.428; BSA = 0.449; body mass index = 0.266) eliminated the association of the
      indexed variable with body size. Indexation by BW best removed the influence of
      all measures of body size. The proportion of variance of LAD explained by BW was
      21.4% compared with only 3.9% for HT. There were minor, but statistically
      significant, age-, gender-, and obesity-related differences in the indexed left
      atrial size (e.g., optimal allometric exponent for BW in male patients = 0.257
      vs. in female patients = 0.253). CONCLUSION: The standard isometric corrections
      for body size fail to adequately account for the associations between LAD and
      body size, and in fact increase the relationship of the indexed parameter to all
      body size measures. Normalization using the optimal allometric exponent removes
      the effect of that variable, with BW best removing the effect of body size.

PMID- 18329847
TI  - Abnormal segmental relaxation patterns in hypertensive disease and symptomatic
      diastolic dysfunction detected by strain echocardiography.
AB  - BACKGROUND: An abnormal segmental relaxation pattern exists as an early sign of
      diastolic dysfunction (DD), detectable by strain (S) echocardiography. OBJECTIVE:
      The objective of this study was to investigate the relation of segmental
      relaxation patterns with longitudinal systolic function and symptomatic DD in
      patients with hypertension (HTN). METHODS: We evaluated 30 healthy volunteers and
      78 volunteers with HTN, divided as follows: (1) patients without DD (n: 28); (2)
      patients with asymptomatic DD (n: 25); and (3) patients with symptomatic DD (n:
      25). All groups had normal ejection fraction greater than or equal to 55%. The
      symptomatic group had mild exertional dyspnea. All participants underwent 2
      dimensional and color Doppler myocardial imaging, and the mean longitudinal
      strain (S) and S rate (SR) were estimated. Early and late diastolic SR parameters
      (SR(E) and SR(A)) were also recorded from the basal, mid, and apical segments for
      each wall. Altered segmental relaxation (SR(E)/SR(A) < 1.1) was regarded as an
      index of segmental DD. RESULTS: Patients who were symptomatic with DD were found
      to have more segments with an abnormal relaxation pattern (segmental DD) and more
      deteriorated longitudinal systolic function based on S and SR, compared with
      patients with asymptomatic HTN and control subjects. Segmental DD was correlated
      with structural changes of left ventricular (LV) remodeling such as wall
      thickness (r: 0.64), relative wall thickness (r: 0.58), and LV mass index (r:
      0.59), as well as mean S (r: -0.61), SR (r: -0.62), systolic blood pressure (r:
      0.44), age (r: 0.49), and filling pressures (r: 0.50), all P less than .01. In
      multiple regression analysis, segmental DD and systolic blood pressure were
      independently related to symptomatic status (segmental DD: beta = 0.33, P = .003;
      systolic blood pressure: beta = 0.24, P = .009, R(2): 0.33). Compared with
      conventional indices of DD (deceleration time of the E wave, isovolumic
      relaxation time, E, A, and E/A), segmental DD was the only parameter that
      predicted symptomatic status (coefficient: 0.3817, SE: 0.1101, P = .0005, odds
      ratio: 1.4648, 95% confidence interval: 1.1761-1.7485). CONCLUSION: LV segmental
      relaxation demonstrates progressive deterioration in HTN disease, which is more
      pronounced in patients with symptomatic DD. Altered segmental relaxation is
      related to structural changes of LV remodeling and constitutes an independent
      predictor for the presence of a symptomatic status.

PMID- 18329848
TI  - Contrast echocardiography: evidence for clinical use.
AB  - The failure of echocardiography to give diagnostically useful information in a
      significant proportion of patients has led to the development of specific
      contrast agents to enhance imaging. Suitable contrast media must have the ability
      to modify ultrasound characteristics, be capable of crossing the pulmonary
      capillary bed, show stability over the duration of a procedure, offer low blood
      solubility with low toxicity and be rapidly eliminated. The current generation of
      ultrasound contrast agents comprises microbubbles of a high molecular-weight gas
      encapsulated in a shell of phospholipid or protein. A review of the clinical
      evidence shows that these agents are clinically effective in enhancing
      echocardiographic imaging. They enable the rescue of failed procedures, often
      sparing patients from invasive tests, but appear not to add to the burden of side
      effects. Indeed, the benefits of using contrast agents in stress echocardiography
      have been recommended in recently published American Society of Echocardiography
      guidelines. Myocardial contrast echocardiography has now developed to the stage
      where assessment of myocardial perfusion for the detection of coronary artery
      disease is possible with the same diagnostic accuracy as radionuclide imaging.
      However, in comparison with the latter technique, it is less expensive, is more
      portable, and avoids the use of ionizing radiation. It is precisely the ability
      of myocardial contrast echocardiography to simultaneously assess function and
      perfusion at the bedside that has given it a unique role in clinical practice.
      This review provides an overview of the clinical evidence supporting the efficacy
      of contrast echocardiography in the assessment of myocardial structure, function,
      and perfusion.

PMID- 18329849
TI  - Ceap/BLOS2 interacts with BRD7 and selectively inhibits its transcription
      suppressing effect on cellular proliferation-associated genes.
AB  - The centrosome associated protein Ceap-16 (also termed BLOS2) can accelerate the
      proliferation of mouse fibroblast NIH3T3 cells, which mechanism remains unclear.
      Here we identified tumor suppressor candidate BRD7 (bromodomain containing
      protein 7), which could negatively regulate cell proliferation and growth, as a
      novel Ceap-16-interacting protein. Ceap-16 and BRD7 interacted with each other
      both in vitro and in vivo. The C-terminus of BRD7 and the central region of Ceap
      16 mediated the interaction. Through this binding, Ceap-16 could translocate from
      cytoplasm to the nucleus where it selectively inhibited the transcriptional
      suppression activity of BRD7 towards certain target genes including E2F3 and
      cyclin A. Moreover, Ceap-16, BRD7 and histone H3/H4 could form a complex and Ceap
      16 did not compete with BRD7 binding to histones. These findings suggest a novel
      function for Ceap-16 in the transcriptional regulation through associating with
      BRD7.

PMID- 18329850
TI  - Seemingly paradoxical seasonal influences on vitamin D status in nursing-home
      elderly people from a Mediterranean area.
AB  - OBJECTIVE: We investigated vitamin D status in institutionalized elderly subjects
      by measuring serum 25-hydroxyvitamin D (25[OH]D) and its association with season
      and other factors: age, gender, nutritional status, cognitive function,
      functional ability, dietary intake, vitamin D supplement consumption, and
      disease. METHODS: The cross-sectional study included 86 subjects, 65-94 y of age
      (29 men and 57 women), who lived in three nursing homes in Murcia, a Spanish
      Mediterranean area. The Mini Nutritional Assessment, Short Portable Mental Status
      Questionnaire, and BI were used to evaluate nutritional status, functional
      ability, and cognitive function, respectively. Serum 25(OH)D concentrations were
      used to assess vitamin D status. The thresholds of inadequacy were considered to
      be <25 nmol/L (vitamin D deficiency) and <50 nmol/L (vitamin D insufficiency).
      RESULTS: Body mass index was 28.8 +/- 5.8 kg/m(2) (mean +/- SD). Vitamin D
      dietary intake was very much below the recommended dietary intake. The Mini
      Nutritional Assessment was 23.6 +/- 4.0, cognitive function was 7.8 +/- 1.9, and
      functional ability 82.9 +/- 23.1. The percentages of subjects with inadequate
      serum 25(OH)D concentrations were 58.2% and 32.6%, taking into consideration
      cutoffs of 50 and 25 nmol/L, respectively. Vitamin D deficiency was more common
      in women (40.3%) than in men (20.7%). Serum 25(OH)D concentrations varied
      significantly with the season in which the samples were taken, but not with the
      other factors analyzed. CONCLUSION: In this Mediterranean area, a substantial
      percentage of institutionalized subjects showed an inadequate vitamin D status,
      which could be remedied by the consumption of vitamin D-fortified foods and/or
      vitamin D supplements, especially during the summer months.

PMID- 18329851
TI  - Glucosyl hesperidin prevents endothelial dysfunction and oxidative stress in
      spontaneously hypertensive rats.
AB  - OBJECTIVE: Glucosyl hesperidin (G-hesperidin), a water-soluble hesperidin
      derivative, has antihypertensive effects. A detailed understanding of the
      mechanism of the blood pressure-lowering effect, however, remains obscure. The
      aim of this work was to investigate the underlying mechanisms involved in the
      hypotensive effect of G-hesperidin in spontaneously hypertensive rats (SHRs) and
      normotensive Wistar-Kyoto rats (WKYs). METHODS: Fourteen-week-old SHRs and WKYs
      were fed a control or G-hesperidin (50 mg/kg) diet for 8 wk. Blood pressure was
      recorded weekly. After 8 wk, the vasodilatory responses of isolated aortas to
      acetylcholine and sodium nitroprusside were assessed. Expression of mRNAs related
      to regulation of blood pressure and vascular tone in the aorta also was
      investigated. Urinary 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker,
      was measured. Cardiac and vascular hypertrophies were observed. RESULTS: In SHRs,
      the ingestion of G-hesperidin inhibited the development of hypertension. G
      hesperidin enhanced endothelium-dependent vasodilation in response to
      acetylcholine, but had no effect on endothelium-independent vasodilation in
      response to sodium nitroprusside. G-hesperidin decreased mRNA expression of
      nicotinamide adenine dinucleotide phosphate oxidase subunits in aorta, which are
      the main source of superoxide anion in the vasculature; endothelial nitric oxide
      synthase expression was unchanged. Urinary 8-hydroxy-2'-deoxyguanosine was
      reduced significantly by G-hesperidin treatment. G-hesperidin suppressed cardiac
      and vascular hypertrophies. In contrast, G-hesperidin had no effects in WKYs.
      CONCLUSION: Continuous ingestion of G-hesperidin reduces oxidative stress by
      inhibiting nicotinamide adenine dinucleotide phosphate oxidase expression in the
      vasculature, thereby ameliorating endothelial dysfunction and hypertension in
      SHRs.

PMID- 18329852
TI  - Effects of omega-3 fatty acids on inflammatory mediators and splenocyte cytokine
      mRNA expressions in rats with polymicrobial sepsis.
AB  - OBJECTIVES: Many studies have shown that omega-3 fatty acids (FAs) have
      immunomodulatory effects. However, the influence of omega-3 FAs on septic
      conditions is not certain. This study examined the effect of fish oil (FO)
      enriched diets before and/or omega-3 FA-containing total parenteral nutrition
      (TPN) after sepsis on the distribution of T-lymphocyte subpopulations and
      splenocyte cytokine mRNA expressions in rats with polymicrobial sepsis. METHODS:
      Rats were assigned to a control group and four experimental groups. The control
      group and groups 1 and 2 were fed a semipurified diet, and groups 3 and 4 had 20%
      soybean oil replaced by FO. After feeding the diets for 10 d, sepsis was induced
      by cecal ligation and puncture (CLP) in the experimental groups, whereas sham
      operation was performed on the control group. TPN was maintained for 3 d after
      CLP or sham operation. The control group and groups 1 and 3 were infused with
      conventional TPN, whereas the TPN solution of groups 2 and 4 was supplemented
      with FO. All rats were sacrificed 3 d after the operation to examine their immune
      responses. RESULTS: Messenger RNA expressions of interleukin-2 and tumor necrosis
      factor-alpha in splenocytes were higher in groups 3 and 4 than in the control
      group and group 1. Interleukin-10 mRNA expression in group 3 was higher than in
      the control group and group 2. Blood CD4 percentage and CD4/CD8 ratio in group 1
      were significantly lower, whereas no differences were observed in FO-supplemented
      groups compared with the control group. CONCLUSION: FO administration before
      and/or after CLP maintained blood T-lymphocyte subpopulations and modulated T
      helper type 1 and 2 cytokine mRNA expressions in rats with polymicrobial sepsis.

PMID- 18329853
TI  - Carbohydrate intake is the main determinant of growth in infants born <33 weeks'
      gestation when protein intake is adequate.
AB  - OBJECTIVE: We investigated the relative contribution of macronutrients to
      postnatal growth in preterm infants born <33 wk of gestation. METHODS: An audit
      of daily parenteral and enteral intakes of protein, carbohydrate, fat, energy,
      and growth (daily weight, weekly length, and head circumference) from birth to
      discharge home in 138 infants at <33 wk of gestation admitted to an Australian
      tertiary hospital was done. A mixed-model analysis of variance with random
      effects (slope and intercept) for subject and controlling for time, sex,
      gestational age, and total energy was used to determine the relative contribution
      of macronutrients to growth. RESULTS: A higher energy intake (kilocalories per
      day) had a positive influence on growth. With total energy held constant, the
      contribution of carbohydrate to total energy had a positive relation to weight,
      length, and head circumference gains; protein had no relation and fat was
      negatively associated. For every 1% increase in energy from carbohydrate, there
      was a 2.3-g/d increase in weight (95% confidence interval 1.6-3.0, P < 0.0001), a
      0.013-cm/d increase in length (95% confidence interval 0.003-0.022, P = 0.007),
      and a 0.015-cm/d increase in head circumference (95% confidence interval 0.009
      0.022, P < 0.0001). CONCLUSION: A re-examination of the macronutrient balance in
      the diet of preterm infants is required in relation to optimizing growth.

PMID- 18329854
TI  - Effect of bilateral sagittal split ramus osteotomy setback on the soft palate and
      pharyngeal airway space.
AB  - To evaluate the effect of bilateral sagittal split ramus osteotomy setback on the
      morphology of the pharyngeal airway, especially the structures of the soft palate
      and pharyngeal airway space (PAS), lateral cephalograms obtained from 49 women
      before treatment and 1 year after surgery were traced and compared. All patients
      underwent this osteotomy to correct mandibular hyperplasia. The data were
      corrected with the use of regression equations for the PAS, taking into account
      head posture. On average, the SNB angle decreased by 3.9 degrees, resulting in an
      increase of 4.1 degrees in OPT/NSL (head posture, defined as the craniocervical
      angulation at the uppermost part of the cervical spine). The morphology of the
      PAS and soft palate changed significantly (p<0.01). The mean reduction in the PAS
      was 2.6mm retropalatinally and 4.0mm retrolingually. On average, the soft-palate
      length increased by 3.2mm and the soft-palate angle increased by 4 degrees. These
      results show that mandibular setback surgery markedly decreases the PAS and
      changes the morphology of the soft palate.

PMID- 18329855
TI  - Omega-O-acylceramide, a lipid essential for mammalian survival.
AB  - The prevention of water loss through the skin is critical for terrestrial
      mammalian species. This function is served by the epidermal permeability barrier,
      which resides primarily in the extracellular domains of the stratum corneum, the
      outermost layer of skin, and its highly ordered lamellar membranes composed
      primarily of free fatty acids, cholesterol, and ceramides (Cer). The dominant
      lipids in these lamellae are Cer, which comprise a heterogeneous group of
      chemically distinct species. One particular subfamily of Cer, which is unique to
      the outer layers of the epidermis of terrestrial mammals, is omega (omega)-O
      acylCer (or acylCer). Myriad evidence suggests that these acylCer play critical
      roles in barrier function. The formation of these epidermal acylCer requires
      several metabolic steps, including synthesis of very long chain fatty acids,
      omega-hydroxylation of the fatty acids, and esterification at the omega-hydroxy
      group with primarily linoleic acid. The authors previously demonstrated that a
      cytochrome P-450-type enzyme is involved in omega-hydroxylation during acylCer
      generation and that inhibition of omega-hydroxylation leads to a barrier
      abnormality in murine epidermis. More recently, we discovered that lack of normal
      elongation of very long chain fatty acid (or ELOVL) 4 function in mutant ELOVL4
      knock-in mice causes acylCer deficiency associated with abnormal barrier
      formation and neonatal lethality. These results indicate not only that acylCer
      are critical lipid components for mammalian survival, but also that keratinocytes
      deploy a complex metabolic pathway leading to the formation of these unique Cer.

PMID- 18329856
TI  - Low-level resistance to ciprofloxacin in non-Typhi Salmonella enterica isolated
      from human gastroenteritis in Dakar, Senegal (2004--2006).

PMID- 18329857
TI  - New acridinone derivative with trypanocidal activity.

PMID- 18329858
TI  - Thymol inhibits Candida albicans biofilm formation and mature biofilm.
AB  - Candida albicans has a high propensity to develop biofilms that are resistant to
      traditional antifungal agents. Thymol is credited with a series of
      pharmacological properties including antimicrobial and antifungal effects. As C.
      albicans biofilms are known to be important factors underlying its virulence and
      pathogenicity, the aim of this study was to investigate whether thymol can
      interfere with biofilm formation as well as acting on mature biofilms. Tests of
      C. albicans strains ATCC 3153A and ATCC MYA 2876 showed that thymol interferes
      with the starting phases of biofilm production as well as with mature C. albicans
      biofilms. The metabolic activity of sessile cells was reduced by >90% at twice
      the minimum inhibitory concentration of planktonic cells. As biofilm is a
      multifactorial phenomenon, the multiple mechanisms of thymol (terpenes) could act
      on different steps in the evolution of mature biofilm.

PMID- 18329859
TI  - Guanosine and its modulatory effects on the glutamatergic system.

PMID- 18329860
TI  - Monolayers of the lipid derivatives of isoniazid at the air/water interface and
      the formation of self-assembled nanostructures in water.
AB  - Isoniazid (INH, isonicotinic acid hydrazide) is one of the most commonly used
      anti-tubercular drugs. However, resistance of Mycobacterium tuberculosis strains
      to anti-mycobacterial agents including INH is an increasing problem worldwide.
      Development of new anti-mycobacterial agents thus has attracted attention. Five
      lipid derivatives of INH were prepared in this study. They formed monolayers at
      the air/water interface, and some nanostructures with different morphologies were
      obtained through molecular self-assembly in water. The derivatives included one
      fatty acyl derivative containing a 12-C hydrocarbon-long chain (1), three fatty
      alcohol derivatives with a succinyl as spacer and an 8, 12 or 16-C hydrocarbon
      long chain (2, 3 and 4), and one tetrahydro-2H-1,3,5-thiadiazine-2-thione (THTT)
      derivative containing a 12-C hydrocarbon-long chain (5). The surface pressure
      area isotherms depended on the volume and configuration of heads and the length
      of tails of derivatives. Compound 2 had a relatively large head and a short tail,
      easily standing uprightly at the interface. Under a certain surface pressure, the
      linear polar head groups of 3 could be partly squeezed out and insert into
      subphase because the length of heads were comparable to the one of tails. The
      very long tails of 4 always maintained above the interface and led to a high
      collapse pressure. Compound 5 possessed an extended and large head consisting of
      the THTT and INH groups so that the relatively short tails tilted at the
      interface and difficultly contact with each other. The THTT rings might be partly
      squeezed out and enter into air under a certain surface pressure. The self
      assembly behaviours of derivatives in water depended on the molecular
      configuration and agreed with the corresponding monolayer behaviours. The
      flexible and medium-long tails (1 and 3) led to the derivatives to form nanoscale
      vesicles, though the short or very long tails did not (2 and 4). Interestingly,
      intermolecular hydrogen bonding could occur between the molecules of 5, and
      improve the derivative forming helical nanofibres other than vesicles. The
      molecular self-assembly of INH's lipid derivatives was explored in details in
      this study. The formation mechanisms of self-assembled nanostructures were
      analyzed. Various types of self-assembled nanostructures were obtained and the
      formation mechanisms were analyzed. The relationship between the self-assembly
      and the molecular configuration of amphiphilic derivatives was also revealed. The
      lipid derivatives of INH show promising anti-Mycobacterium action because the
      amphiphilic prodrugs allow for better penetration of the bacterial cells. The
      self-assembled nanostructures may likely be the potential self-assembled drug
      delivery systems for tuberculosis therapy.

PMID- 18329861
TI  - Pharmaceutical gel analysis by NIR spectroscopy. Determination of the active
      principle and low concentration of preservatives.
AB  - Near infrared spectroscopy has proved highly suitable for the analysis of
      pharmaceutical formulations. However, its limited sensitivity can severely
      restrict its scope of application. In this work, we determine the active
      principle and two preservatives in a pharmaceutical preparation available as a
      hydrogel. The matrix of the pharmaceutical preparation exhibits strong absorption
      in the NIR spectral region; also, the two preservatives (parabens) are very
      similar in chemical and spectral terms, and present at low concentrations in the
      pharmaceutical. These complications make it rather difficult to accurately
      quantify the active principle and the preservatives, which can only be
      accomplished by using an effective design in order to prepare the samples to be
      included in the calibration set and select the optimum spectral range for
      measuring each analyte. The evaporation of solvents during the measurement
      process produces increasing errors related with sample's air exposition; the
      introductions of new samples with a wider range of the volatile components
      correct this effect. An ANOVA of the predictions obtained with the new models
      shows that correct the error due to evaporation. The proposed method was
      validated for the analytical control of the studied preparation.

PMID- 18329862
TI  - Protein delivery using nanoparticles based on microemulsions with different
      structure-types.
AB  - Poly(alkylcyanoacrylate) nanoparticles based on microemulsions with different
      structure-types and containing insulin as a model protein were prepared and
      characterised in this study. A phase diagram of the pseudoternary system
      isopropyl myristate, caprylocaproyl macrogolglycerides, polyglycerol oleate and
      water was established. All compounds used in this study were pharmaceutically
      acceptable and biocompatible. The area in the phase diagram containing optically
      isotropic, monophasic systems was designated as the microemulsion region. Systems
      within this region were identified as water-in-oil (w/o), bicontinuous and oil-in
      water (o/w) microemulsions with viscosity, conductivity, differential scanning
      calorimetry and self-diffusion NMR. The size distributions of the resulting
      nanoparticles prepared by interfacial polymerisation from selected microemulsions
      using ethyl (2) cyanoacrylate and butyl (2) cyanoacrylate were unimodal but
      template- and monomer-dependent and ranged from 160 to 400 nm. Entrapment and
      release of insulin were also studied. Entrapment ranged from 11.5 to 20.9% and a
      near zero-order release was observed after an initial burst. Release of insulin
      was monitored for 6h. Insulin-loaded nanoparticles were 320-350 nm in size. The
      microemulsion-structure was retained during the polymerisation process as
      determined by NMR. This study showed that these microemulsions with flexible
      formulation possibilities for the solubilisation of peptides and proteins
      depending on their microstructure could serve well as a platform for designing
      encapsulation processes for oral delivery of insulin.

PMID- 18329863
TI  - [Neurological complications in Down syndrome].
AB  - The aim of this study was to look over the neurological disorders associated with
      Down syndrome. MATERIAL AND METHOD: We reviewed 12 patients with Down syndrome
      hospitalized from 1997 to 2003, suffering from various neurological
      complications. RESULTS: Among the 5 patients with epilepsy, 3 presented with West
      syndrome and 2 with partial epilepsy; after treatment all were seizure-free. Four
      patients had ischemic lesions; 1 presented with Moya-Moya syndrome. Four patients
      presented with C1-C2 vertebral dislocation; all underwent surgery. One of the
      patients with epilepsy had neurological ischemic sequelae. CONCLUSION: West
      syndrome is the most frequent type of epilepsy encountered in Down syndrome.
      Outcome is favourable if appropriate treatment is initiated early. Any suspicion
      or sign of vascular lesion in patients with Down syndrome should be promptly
      investigated. The hyperlaxity associated with Down syndrome could lead to C1-C2
      dislocation and a systematic screening is mandatory in order to avoid
      neurological complications.

PMID- 18329864
TI  - [The psychological experience of the mothers whose babies were born deformed in
      the neonatological ward of the academic hospital center of Treichville (Cote
      d'Ivoire)].
AB  - OBJECTIVE: When a baby is born deformed, his birth breaks up plans his family has
      made for his life as well as for the family itself. So, our objective was to
      describe the experience undergone by the mothers who gave birth to babies with
      serious deformities. METHOD: A prospective and descriptive study was carried out
      during 12 months about 35 mothers whose babies were born seriously deformed. The
      data were collected from newborn's medical file and from a well-conducted
      interview with volunteered mothers. RESULTS: The incidence of the major
      deformities was 1.4% and the antenatal diagnosis was carried out on only 6 cases.
      The announcement of deformities in the 30 cases discovered at birth by the
      clinical staff brought about a shock among mothers. In fact, 28 mothers were
      disappointed, while 23 experienced fear and 10 others felt guilty. Six mothers
      thought in terms of aborting, followed by 25 mothers who without any
      psychological aid felt lonely. Furthermore, 30 mothers suffered from a lack of
      communication with nurses and with medical staff concerning deformities. The
      anxiety of mothers was linked, respectively to fear of their husband (33 cases),
      to the social environment (35 cases) and to the health care (10 cases).
      CONCLUSION: Mothers facing congenital deformity experienced painful and violent
      emotional distress. Therefore, the emphasis must be put on the improvement of the
      neonatal diagnosis and of relationship between physicians and parents in order to
      achieve a close support toward mothers.

PMID- 18329865
TI  - [Aplasia cutis congenita of the scalp (5 observations)].
AB  - Aplasia cutis congenita (ACC) is an uncommon congenital malformation. It is
      characterized by defects of the skin that occur most frequently on the scalp
      along the midline, but can also be localized on the trunk, face and limbs,
      usually with a symmetrical distribution. When it is localized in the skull, it
      can extend to the dura mater, with only the thin pia mater to protect the brain.
      PATIENTS AND METHODS: We report a retrospective study during a period of 10 years
      and we report 5 cases of ACCV hospitalized in the pediatric service in CHU Hedi
      Chaker and in maxillo-facial surgery service in CHU Habib Bourguiba, Sfax. We
      studied the epidemiologic, clinical, and therapeutic aspects in our patients.
      RESULTS: The average age at the admission was 5 days (2-8 days). A consanguinity
      was found in 2 cases. The clinical examination revealed cutaneous and osseous
      structures aplasia located in frontoparietal zone in 3 patients and in parieto
      occipital zone in a patient. A hypoplasia of the toes was noted in 3 cases and a
      hypoplasia of the 3rd finger of the 2 hands in a case. Plain X-ray skull (3
      cases) showed the osseous defect in all the cases. The cerebral IRM (2 cases)
      showed osseous and cutaneous defect in two cases and a lipome of the corpus
      callosum in one patient. A surgical repair using a cutaneous graft was performed
      for 3 patients. A patient died on the 16th day of life from a haemorrhage of the
      longitudinal sinus. The evolution was favourable in 4 cases with a cicatrisation
      of good quality but with subsequent alopecia. CONCLUSION: ACC of the scalp is a
      rare and often sporadic affection. Our experience confirms that fatal bleeding
      from the longitudinal sinus can occur during the 1st weeks of life.

PMID- 18329866
TI  - [Haemophilia in a newborn with inhabitual clinic presentation].

PMID- 18329867
TI  - [Hereditary angioedema causing colocolic intussusception].
AB  - Hereditary angioedema is a rare, autosomal dominant disease inherited. The cause
      is a quantitative or qualitative congenital deficit in C1 inhibitor. Various
      clinical symptoms, in particular of sub-cutaneous, upper airways and digestive
      origin, have been described. Life threatening conditions may be observed. Little
      information is available on digestive tract localization corresponding to
      intestinal intussusception associated with hereditary angioedema in children. We
      report a case of hereditary angioedema observed in a 15-years-old girl who
      presented such features. We propose a review of the literature and discuss the
      curative treatment of digestive crisis in children with hereditary angioedema.

PMID- 18329868
TI  - Assessment of classification improvement in patients with Alzheimer's disease
      based on magnetoencephalogram blind source separation.
AB  - OBJECTIVES: In this pilot study, we intended to assess whether a procedure based
      on blind source separation (BSS) and subsequent partial reconstruction of
      magnetoencephalogram (MEG) recordings might enhance the differences between MEGs
      from Alzheimer's disease (AD) patients and elderly control subjects. MATERIALS
      AND METHODS: We analysed MEG background activity recordings acquired with a 148
      channel whole-head magnetometer from 21 AD patients and 21 control subjects.
      Artefact-free epochs of 20 s were blindly decomposed using the algorithm for
      multiple unknown signals extraction (AMUSE), which arranges the extracted
      components by decreasing linear predictability. Thus, the components of diverse
      epochs and subjects could be easily compared. Every component was characterised
      with its median frequency and spectral entropy (denoted by fmedian and SpecEn,
      respectively). The differences between subject groups in these variables were
      statistically evaluated to find out which components could improve the subject
      classification. Then, these significant components were used to partially
      reconstruct the MEG recordings. RESULTS: The statistical analysis showed that the
      AMUSE components which provided the largest differences between demented patients
      and control subjects were ordered together. Considering this analysis, we defined
      two subsets, denoted by BSS-{15,35} and BSS-{20,30}, which included 21 components
      (15-35) and 11 components (20-30), respectively. We partially reconstructed the
      MEGs with these subsets. Then, the classification performance was computed with a
      leave-one-out cross-validation procedure for the case where no BSS was applied
      and for the partial reconstructions BSS-{15,35} and BSS-{20,30}. The BSS and
      component selection procedure improved the classification accuracy from 69.05% to
      83.33% using f(median) with BSS-{15,35} and from 61.91% to 73.81% using SpecEn
      with BSS-{20,30}. CONCLUSION: These preliminary results lead us to think that the
      proposed procedure based on BSS and selection of significant components may
      improve the classification of AD patients using straightforward features from MEG
      recordings.

PMID- 18329869
TI  - Control of protein synthesis and mRNA degradation by microRNAs.
AB  - MicroRNAs represent a large family of non-coding small RNAs that function as the
      major endogenous triggers for RNA interference. Hundreds of microRNAs have been
      identified through small RNA cloning, bioinformatic predictions, and high
      throughput pyrosequencing. They are believed to suppress gene expression through
      post-transcriptional regulation via either translational repression or mRNA
      turnover. Over one third of human genes are predicted targets for microRNAs.
      However, even after extensive studies, the function of microRNAs and the precise
      mechanism by which they suppress gene expression remain elusive. Although
      controversy remains, recent advances have shined new light on how microRNAs
      regulate their targets. A better understanding of the mechanism should facilitate
      studies of their function.

PMID- 18329870
TI  - The Decapentaplegic morphogen gradient: a precise definition.
AB  - Two key processes are in the basis of morphogenesis: the spatial allocation of
      cell types in fields of naive cells and the regulation of growth. Both are
      controlled by morphogens, which activate target genes in the growing tissue in a
      concentration-dependent manner. Thus the morphogen model is an intrinsically
      quantitative concept. However, quantitative studies were performed only in recent
      years on two morphogens: Bicoid and Decapentaplegic. This review covers
      quantitative aspects of the formation and precision of the Decapentaplegic
      morphogen gradient. The morphogen gradient concept is transitioning from a soft
      definition to a precise idea of what the gradient could really do.

PMID- 18329871
TI  - HP1: a functionally multifaceted protein.
AB  - HP1 (heterochromatin protein 1) is a nonhistone chromosomal protein first
      discovered in Drosophila melanogaster because of its association with
      heterochromatin. Numerous studies have shown that such a protein plays a role in
      heterochromatin formation and gene silencing in many organisms, including fungi
      and animals. Cytogenetic and molecular studies, performed in Drosophila and other
      organisms, have revealed that HP1 associates with heterochromatin, telomeres and
      multiple euchromatic sites. There is increasing evidence that the different
      locations of HP1 are related to multiple different functions. In fact, recent
      work has shown that HP1 has a role not only in heterochromatin formation and gene
      silencing, but also in telomere stability and in positive regulation of gene
      expression.

PMID- 18329872
TI  - On helicases and other motor proteins.
AB  - Helicases are molecular machines that utilize energy derived from ATP hydrolysis
      to move along nucleic acids and to separate base-paired nucleotides. The movement
      of the helicase can also be described as a stationary helicase that pumps nucleic
      acid. Recent structural data for the hexameric E1 helicase of papillomavirus in
      complex with single-stranded DNA and MgADP has provided a detailed atomic and
      mechanistic picture of its ATP-driven DNA translocation. The structural and
      mechanistic features of this helicase are compared with the hexameric helicase
      prototypes T7gp4 and SV40 T-antigen. The ATP-binding site architectures of these
      proteins are structurally similar to the sites of other prototypical ATP-driven
      motors such as F1-ATPase, suggesting related roles for the individual site
      residues in the ATPase activity.

PMID- 18329873
TI  - Risk of second malignant neoplasms after childhood central nervous system
      malignant tumours: an international study.
AB  - PURPOSE: The aim of this study was to assess the risk of second malignant
      neoplasms (SMNs) other than central nervous system (CNS) neoplasms after
      childhood CNS cancer in an international multicentre study. METHODS: Individual
      data on cases of CNS cancer in children (0-14 years) and on subsequent SMNs were
      obtained from 13 population-based cancer registries contributing data for
      different time periods in 1943-2000. Standardised incidence ratios (SIRs) with
      95% confidence intervals (CI), absolute excess risk and cumulative incidence of
      SMNs were computed. RESULTS: We observed 43 SMNs in 8431 CNS cancer survivors.
      The SIR was 10.6 (4.85-20.1) for thyroid cancer (nine cases), 2.75 (1.01-5.99)
      for leukaemia (six cases) and 2.47 (0.90-5.37) for lymphoma (six cases). The SIRs
      were highest in the first 10 years after CNS cancer diagnosis. The cumulative
      incidence of non-CNS SMNs was 3.30% (0.95-5.65%) within 45 years after a CNS
      cancer diagnosis. Within 15 years, the cumulative incidence was highest for cases
      diagnosed after 1980 (0.56%, 95% CI: 0.29-0.82%). CONCLUSION: This population
      based study indicates that about one every 180 survivors of a childhood CNS
      cancer will develop a non-CNS SMN within the following 15 years. The excess is
      higher after glioma and embryonal malignant tumour than after another CNS tumour.

PMID- 18329874
TI  - Androstenedione production by biotransformation of phytosterols.
AB  - Androstenedione is a key intermediate of microbial steroid metabolism. It belongs
      to the 17-keto steroid family and is used as starting material for the
      preparation of different steroids. Androstenedione can be produced by microbial
      side chain cleavage of phytosterol, which is an alternative to multi-step
      chemical synthesis. In this review, various methods of biotransformation of
      sterols to androstenedione are surveyed. It begins with the history and current
      research status in this field. The existing methods of chemical and biochemical
      synthesis are examined. Various issues related to these methods and how
      researchers have addressed them is presented. Among these, the low solubility of
      sterols in aqueous systems is a critical problem since it limits the product
      yield. The main content of this review focuses on new methods of
      biotransformation that are being investigated. Recent biotechnological advances
      in this field are presented. The review ends with a note on future perspectives.

PMID- 18329875
TI  - Effects of inorganic nutrient levels on the biodegradation of benzene, toluene,
      and xylene (BTX) by Pseudomonas spp. in a laboratory porous media sand aquifer
      model.
AB  - The effect of inorganic nutrients (sulfate, phosphate, and ammonium chloride) on
      the aerobic biodegradation of benzene, toluene, and xylene (BTX) by Pseudomonas
      spp. was studied in the laboratory using a glass sand tank. The increase of
      nutrient levels resulted in enhanced bacterial growth and BTX degradation.
      Sulfate and phosphate serve as key electron acceptors in the microbiological
      processes degrading BTX. The observed bacterial morphological changes during BTX
      degradation reveal that the filamentous bacteria were the dominant species at low
      temperatures about 20 degrees C. The spherical and rod-shaped cells became
      dominant at higher temperatures ranging from 25 degrees C to 28 degrees C. When
      the BTX mixture was allowed to be biodegraded for longer incubation periods of 21
      42 h at high phosphate concentrations, large amounts of rod-shaped cells were
      clustered. The morphological adaptation appears to be controlled by the
      temperature and nutrient levels in the sandy medium where Pseudomonas spp.
      thrives.

PMID- 18329876
TI  - Sulfonamidolactam inhibitors of coagulation factor Xa.
AB  - As part of an effort to identify novel backups for previously reported pyrazole
      based coagulation Factor Xa inhibitors, the pyrazole 5-carboxamide moiety was
      replaced by 3-(sulfonylamino)-2-piperidone. This led to the identification of a
      structurally diverse chemotype that was further optimized to incorporate neutral
      or weakly basic aryl and heteroaryl P1 groups while maintaining good potency
      versus Factor Xa. Substitution at the sulfonamide nitrogen provided further
      improvements in potency and as did introduction of alternate P4 moieties.

PMID- 18329877
TI  - Ryanodine receptor arrays: not just a pretty pattern?
AB  - Ryanodine receptors (RyRs) are colossal membrane protein complexes that reside in
      the endoplasmic reticulum of skeletal and cardiac muscle myocytes and neurons, in
      addition to many non-excitable cells. They comprise high-conductance ion channels
      that mediate the massive release of Ca2+ ions from the endoplasmic reticulum into
      the cytoplasm. This is the trigger for contraction during each muscle excitation
      contraction coupling cycle. Individual RyRs are believed to network with other
      RyRs indirectly, through diffusion of released Ca2+ ions, namely the Ca2+-induced
      Ca2+ release phenomenon. However, RyRs can intrinsically organize into a regular
      array resembling a distinctive checkerboard pattern, with each square-shaped
      receptor appearing to abut four neighbours at each corner. In this opinion
      article, we describe recent data showing structural interactions between RyR
      oligomers in reconstituted arrays, and we suggest that this provides strong
      evidence for direct inter-RyR communication through a novel, allosteric
      regulatory mechanism.

PMID- 18329878
TI  - Postural adaptations to repeated optic flow stimulation in older adults.
AB  - The purpose of this study is to understand the processes of adaptation (changes
      in within-trial postural responses) and habituation (reductions in between-trial
      postural responses) to visual cues in older and young adults. Of particular
      interest were responses to sudden increases in optic flow magnitude. The postural
      sway of 25 healthy young adults and 24 healthy older adults was measured while
      subjects viewed anterior-posterior 0.4 Hz sinusoidal optic flow for 45 s. Three
      trials for each of three conditions were performed: (1) constant 12 cm optic flow
      amplitude (24 cm peak-to-peak), (2) constant 4 cm amplitude (8 cm p-t-p), and (3)
      a transition in amplitude from 4 to 12 cm. The average power of head sway
      velocity (P(vel)) was calculated for consecutive 5s intervals during the trial to
      examine the changes in sway within and between trials. A mixed factor repeated
      measures ANOVA was performed to examine the effects of subject Group, Trial, and
      Interval on the P(vel). P(vel) was greater in older adults in all conditions
      (p<0.001). During the 12 cm constant amplitude trials, within-trial adaptation
      occurred for all subjects, but there were differences in the between-trial
      habituation. P(vel) of the older adults decreased significantly between all 3
      trials, but decreased only between Trials 1 and 2 in young adults. While the
      responses of the young adults to the transition in optic flow from 4 to 12 cm did
      not significantly change, older adults had an increase in P(vel) following the
      transition, ranging from 6.5 dB for the first trial to 3.4 dB for the third
      trial. These results show that older adults can habituate to repeated visual
      perturbation exposures; however, this habituation requires a greater number of
      exposures than young adults. This suggests aging impacts the ability to quickly
      modify the relative weighting of the sensory feedback for postural stabilization.

PMID- 18329879
TI  - Glioblastoma multiforme of the conus medullaris with holocordal spread.
AB  - Glioblastoma multiforme of the conus medullaris is rare. It spreads both locally
      to contiguous structures and also by cerebrospinal seeding. The disease is
      aggressive and the ultimate prognosis is dismal. We report a case of conus
      medullaris glioblastoma multiforme with involvement of the holocord. In spite of
      excision of the conus medullaris tumor followed by radiation, the disease
      continued to progress rapidly. We discuss the rarity of the disease and the
      related literature with regard to treatment modalities.

PMID- 18329880
TI  - Asymptomatic spontaneous rupture of craniopharyngioma cyst.
AB  - Spontaneous rupture of craniopharyngioma cyst is a rare phenomenon. Either
      chemical meningitis or neurological improvement is usually associated with
      spontaneous cyst rupture. We experienced two patients who underwent asymptomatic
      spontaneous cyst rupture. MRI revealed reductions in the sizes of cysts in the
      left cerebellopontine cistern and middle fossa in a 4-year-old girl and a cyst in
      the suprasellar region of a 47-year-old man. These patients did not develop
      chemical meningitis, nor was there any change in neurological symptoms related to
      the craniopharyngioma cysts. According to our review of the literature,
      spontaneous rupture of craniopharyngioma cysts can be divided into three
      subtypes: (i) cyst rupture associated with chemical meningitis; (ii) cyst rupture
      with improvement in symptoms related to the craniopharyngioma and not associated
      with chemical meningitis; and (iii) asymptomatic rupture. It is important to be
      aware of unexpected cyst rupture during observation of craniopharyngiomas.

PMID- 18329881
TI  - Cystic acoustic neuromas: surgical outcome in a series of 58 patients.
AB  - We aimed to analyze the clinical characteristics and surgical outcomes of
      surgically treated cystic acoustic neuromas, and to determine the prognostic
      significance of the presence of cystic components, by comparing surgical outcomes
      for solid and cystic tumors. A total of 58 patients (20.4%) with newly diagnosed
      cystic tumor were studied. The surgical outcome was analyzed in terms of extent
      of tumor removal, facial nerve preservation, morbidity and mortality; and was
      compared with that in patients with solid tumors. Facial nerve preservation rates
      were much better for solid tumors (82.7%) than for cystic tumors (67.9%). The
      extent of tumor removal was complete in 75.9% of patients with cystic tumors as
      compared with 90.2% for solid acoustic neuromas. Overall mortality was 8.6%.
      Cystic tumors differ from solid acoustic neuromas by having a rapid growth
      pattern, short clinical history and more frequent facial nerve involvement. They
      are associated with a poorer surgical outcome in terms of facial preservation and
      overall result.

PMID- 18329882
TI  - A randomised RSA study of Peri-Apatite HA coating of a total knee prosthesis.
AB  - BACKGROUND: In total knee replacement, sound early fixation of the prosthesis is
      crucial for achieving a good long-term result and for minimising the risk of
      loosening. Various types of prosthetic material, different surface textures and
      shapes and the incorporation of screws or pegs have been used to achieve good
      fixation, particularly in the uncemented knee. Hydroxyapatite (HA) coating of
      prosthetic joint components is another technique used to enhance early stability
      and so to improve the longevity of the prosthesis-bone fixation. HA ceramic
      coatings are mostly plasma sprayed onto the fixation surface of the implant.
      Plasma spraying is largely a 'line of sight' technique and as such there are
      difficulties involved when covering three-dimensional planes, such as porous
      beaded fixation surfaces typically found on several knee prostheses. The
      objective of this study was to assess the clinical performance of the solution
      deposited HA coating, Peri-Apatite , with regard to its ability to stimulate an
      endurable and stable implant fixation. PATIENTS AND METHODS: We randomised 60
      patients into two groups; one group received the porous coated prosthesis with
      solution-deposited HA, and the other group received a prosthesis without HA.
      Radiostereometric examination was used as the primary tool for measuring
      migration in the prosthetic components. RESULTS: There was a lower incidence of
      early subsidence in the Peri-Apatite group. At 24 months there were no
      differences in clinical scorings or maximal total point motion. CONCLUSION:
      Addition of solution-deposited HA coating appears to provide better early stable
      fixation in a porous coated knee prosthesis.

PMID- 18329883
TI  - Fixed-bearing versus mobile-bearing total knee arthroplasty: a prospective
      randomised, clinical and radiological study with mid-term results at 7 years.
AB  - Mobile-bearing (MB) total knee arthroplasty (TKA) was developed as an alternative
      to the established fixed-bearing (FB) design because of theoretical advantages.
      Short-term studies comparing these designs have not shown any differences in
      clinical and radiographic results. We compared the results at 7 years of a
      randomised study of patients undergoing TKA using either a FB or a MB variant of
      the same prosthesis. Fifty-two patients (52 knees) with an average age of 70
      years received a FB posterior-stabilized prosthesis, and 50 patients (52 knees)
      with an average age of 72 years, a MB prosthesis. All implants were cemented and
      the patella was routinely resurfaced. Preoperatively, there were no differences
      between the two groups, and surgical procedure and postoperative protocol were
      the same for both. At an average follow-up of 7.1 years, no significant
      differences of FB over MB design could be demonstrated with respect to the
      American Knee Society score (AKSS), pain score, a questionnaire of general health
      (SF-12 score), range of motion (ROM), or complication rates. Radiographs showed
      no significant difference in prosthetic alignment or evidence of loosening. Two
      knees with a MB design required reoperation, one for persistent joint stiffness
      and another to treat septic loosening. One patient with a MB prosthesis with
      signs of tibial component loosening was asymptomatic. We conclude that at mid
      term follow-up there is no evidence to prove the superiority of MB over FB TKA
      with regard to the clinical and radiographic results.

PMID- 18329884
TI  - Potential antitumoral properties of a new copper complex with santonic acid.
AB  - A new copper(II) complex of santonic acid [Cu(2)(sant)(4)(H(2)O)(2)].2(1/2)H(2)O
      has been prepared and characterized by electronic, vibrational, EPR spectral
      studies, and stability determinations in solution. The presence of two
      antiferrromagnetically coupled copper centers in the solid state was detected by
      EPR. The dinuclear Cu(II) complex crystallizes in the tetragonal P4(3)2(1)2 space
      group, with a=b=14.498(3), c=64.07(1)A. Biological studies indicate that the
      complex displays interesting potential antitumoral actions.

PMID- 18329885
TI  - Synthesis and antifungal activity of novel sulfoxide derivatives containing
      trimethoxyphenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety.
AB  - Selective oxidation of sulfides 7 or 8 to sulfoxides 9 or 10 is achieved by
      mCPBA. The structures of the compounds 9 or 10 are confirmed by elemental
      analysis, IR, and (1)H NMR. The bioassay results showed that title compound 10a
      possess high antifungal activities with EC(50) values ranging from 19.91 to 63.97
      microg/mL. The mechanism of action of 10a against Sclerotinia sclerotiorum was
      studied. After treating with compound 10a at 100 microg/mL for 12 h, the mycelial
      reducing sugar, D-GlcNAc, soluble protein and pyruvate content, chitinase
      activity showed declining tendency.

PMID- 18329886
TI  - Internalisation of the mu-opioid receptor by endomorphin-1 and leu-enkephalin is
      dependant on aromatic amino acid residues.
AB  - The opioid receptor system in the central nervous system controls a number of
      physiological processes, most notably pain. However, most opioids currently
      available have a variety of side-effects as well as exhibiting tolerance.
      Tolerance is most likely to be a complex phenomenon, however, the role of
      receptor internalisation is thought to play a crucial role. In this study, we
      examined the role of aromaticity in ligand-mediated receptor internalisation of
      the mu-opioid receptor (MOPR). These studies show that the amount of receptor
      internalisation may be dependant on the amphiphilicity of the ligand.
      Specifically, deletion of the C-terminus aromatic residues of endomorphin 1,
      particularly tryptophan reduces receptor-mediated internalisation whilst the
      addition of tryptophan within the enkephalin sequence increases receptor
      internalisation and decreases tolerance.

PMID- 18329887
TI  - DNA threading bis(9-aminoacridine-4-carboxamides): effects of piperidine
      sidechains on DNA binding, cytotoxicity and cell cycle arrest.
AB  - We describe the synthesis of a series of DNA-threading bis(9-aminoacridine-4
      carboxamides) comprising ethylpiperidino and N-methylpiperidin-4-yl sidechains,
      joined via neutral flexible alkyl chains, charged flexible polyamine chains and a
      semi-rigid charged piperazine linker. Their cytotoxicity towards human leukaemic
      cells gives IC(50) values ranging from 99 to 1100 nM, with the ethylpiperidino
      series generally being more cytotoxic than the N-methylpiperidin-4-yl series.
      Measurements with supercoiled DNA indicate that they bisintercalate.

PMID- 18329888
TI  - Hydrophobic characterization of intracellular lipids in situ by Nile Red
      red/yellow emission ratio.
AB  - Nile Red (9-diethylamino-5H-benzo [alpha] phenoxazine-5-one) is a fluorescent
      lipophilic dye characterized by a shift of emission from red to yellow according
      to the degree of hydrophobicity of lipids. Polar lipids (i.e., phospholipids)
      which are mostly present in membranes, are stained in red whereas neutral lipids
      (esterified cholesterol and triglycerides) which are present in lipid droplets,
      are stained in yellow. Besides this marked, qualitative contrast between polar
      and neutral lipids, small differences of the hydrophobic strength could be
      assessed by the quantitative ratio of red and yellow emissions, in order to
      extend the discrimination of lipids within the groups of neutral and polar
      lipids. On the other hand, ratiometric data of red and yellow emissions have not
      yet been evaluated in the numerous previous light microscopy investigations which
      used Nile Red. In this work we show that the Nile Red red/yellow ratio enables
      discrimination of different lipids (monooleine>oleic
      acid>phosphatidylcholine>free cholesterol>trioleine>oleyl cholesteryl ester). We
      also show changes in the Nile Red red/yellow emission ratio of lipid droplets of
      3T3 mouse fibroblasts induced by drugs interfering with the cholesterol cycle.

PMID- 18329889
TI  - Ganglioside GM1 effects on the expression of nerve growth factor (NGF), Trk-A
      receptor, proinflammatory cytokines and on autoimmune diabetes onset in non-obese
      diabetic (NOD) mice.
AB  - NOD (non-obese diabetic) mice develop type 1 diabetes mellitus spontaneously and
      with a strong similarity to the human disease. Differentiation and function of
      pancreas beta cells are regulated by a variety of hormones and growth factors,
      including the nerve growth factor (NGF). Gangliosides have multiple
      immunomodulatory activities with immunosuppressive properties, decreasing
      lymphoproliferative responses and modulating cytokine production. In the present
      study, serum, pancreas islets and spleen mononuclear cells from NOD mice treated
      with monosialic ganglioside GM1 (100 mg/kg/day) and the group control which
      received saline solution were isolated to investigate the proinflammatory
      cytokines (IL-1beta, IFN-gamma, IL-12, TNF-alpha), NGF and its high-affinity
      receptor TrkA, peri-islet Schwann cells components (GFAP, S100-beta) expression
      and the relationship with diabetes onset and morphological aspects. Our results
      suggest that GM1 administration to female NOD mice beginning at the 4th week of
      life is able to reduce the index of inflammatory infiltrate and consequently the
      expression of diabetes, modulating the expression of proinflammatory cytokines
      (IL-12, IFN-gamma, TNF-alpha and IL-1beta). Furthermore, GM1 increases GFAP, S
      100beta and NGF in pancreas islets, factors involved in beta cell survival.

PMID- 18329890
TI  - One-step affinity tag purification of full-length recombinant human AP-1
      complexes from bacterial inclusion bodies using a polycistronic expression
      system.
AB  - The AP-1 transcription factor is a dimeric protein complex formed primarily
      between Jun (c-Jun, JunB, JunD) and Fos (c-Fos, FosB, Fra-1, Fra-2) family
      members. These distinct AP-1 complexes are expressed in many cell types and
      modulate target gene expression implicated in cell proliferation,
      differentiation, and stress responses. Although the importance of AP-1 has long
      been recognized, the biochemical characterization of AP-1 remains limited in part
      due to the difficulty in purifying full-length, reconstituted dimers with active
      DNA-binding and transcriptional activity. Using a combination of bacterial
      coexpression and epitope-tagging methods, we successfully purified all 12
      heterodimers (3 Junx4 Fos) of full-length human AP-1 complexes as well as c-Jun/c
      Jun, JunD/JunD, and c-Jun/JunD dimers from bacterial inclusion bodies using one
      step nickel-NTA affinity tag purification following denaturation and renaturation
      of coexpressed AP-1 subunits. Coexpression of two constitutive components in a
      dimeric AP-1 complex helps stabilize the proteins when compared with individual
      protein expression in bacteria. Purified dimeric AP-1 complexes are functional in
      sequence-specific DNA binding, as illustrated by electrophoretic mobility shift
      assays and DNase I footprinting, and are also active in transcription with in
      vitro-reconstituted human papillomavirus (HPV) chromatin containing AP-1-binding
      sites in the native configuration of HPV nucleosomes. The availability of these
      recombinant full-length human AP-1 complexes has greatly facilitated mechanistic
      studies of AP-1-regulated gene transcription in many biological systems.

PMID- 18329891
TI  - Periplasmic expression and recovery of human interferon gamma in Escherichia
      coli.
AB  - A synthetic human interferon gamma (hIFN-gamma) gene was fused to SP1 and SP3,
      two Sec-dependent artificial signal peptides to transport the hIFN-gamma to the
      periplasm of Escherichia coli BL21-SI. The processing efficiency of both SP1-hIFN
      gamma and SP3-hIFN-gamma was dependent on the culture medium as well as the post
      induction temperature. Both precursors were processed completely when cells were
      cultured using minimal medium and a post-induction temperature of 32.5 degrees C,
      and only the processed hIFN-gamma was detected. The SP3 signal peptide was more
      efficient than SP1 for the secretion of hIFN-gamma. Sixty percent of the total
      hIFN-gamma was secreted to the periplasm using the SP3 signal peptide and a post
      induction temperature of 20 degrees C. Using Tris-sucrose-dithiothreitol (TSD)
      hypertonic buffer, the periplasmic soluble hINF-gamma was recovered with a purity
      of 85%.

PMID- 18329892
TI  - Vitamin D status: measurement, interpretation, and clinical application.
AB  - Vitamin D, the sunshine vitamin, is now recognized not only for its importance in
      promoting bone health in children and adults but also for other health benefits,
      including reducing the risk of chronic diseases such as autoimmune diseases,
      common cancer, and cardiovascular disease. Vitamin D made in the skin or ingested
      in the diet is biologically inert and requires 2 successive hydroxylations first
      in the liver on carbon 25 to form 25-hydroxyvitamin D [25(OH)D], and then in the
      kidney for a hydroxylation on carbon 1 to form the biologically active form of
      vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. With the identification of
      25(OH)D and 1,25(OH)(2)D, methods were developed to measure these metabolites in
      the circulation. Serum 25(OH)D is the barometer for vitamin D status. Serum
      1,25(OH)(2)D provides no information about vitamin D status and is often normal
      or even increased as the result of secondary hyperparathyroidism associated with
      vitamin D deficiency. Most experts agree that 25(OH)D of <20 ng/mL is considered
      to be vitamin D deficiency, whereas a 25(OH)D of 21-29 ng/mL is considered to be
      insufficient. The goal should be to maintain both children and adults at a level
      >30 ng/mL to take full advantage of all the health benefits that vitamin D
      provides.

PMID- 18329893
TI  - Rapid report on methodology: does loss to follow-up in a cohort study bias
      associations between early life factors and lifestyle-related health outcomes?
AB  - PURPOSE: To examine the consequences of non-response in a follow-up survey for
      associations between early-life factors and lifestyle-related health outcomes in
      adulthood. METHODS: In a cohort of 11532 Danish men born in 1953 we had nearly
      complete follow-up in the National Patient Register, but only 66% of 9507
      eligible cohort members participated in a follow-up survey, in 2004. We examined
      whether characteristics measured early in life and discharge from hospital for
      alcohol abuse or tobacco-related lung diseases, were associated with survey
      response. Associations between the early-life characteristics and these two
      health outcomes were calculated in the entire cohort and among responders, and
      the effect of non-response was described by a Relative Odd Ratio
      (ROR=OR(responders)/OR(entire cohort)). RESULTS: A low response rate at age 50
      years was related to having a single mother at birth, low educational attainment
      at age 18, and low cognitive function at ages 12 and 18. The risk of alcohol
      overuse and tobacco-related diseases was also highest among non-responders.
      However, the associations between early-life characteristics and the outcomes
      were nearly the same in responders as in the entire cohort. CONCLUSIONS: Although
      non-responders differed from responders in terms of early-life exposures and
      incidence of the lifestyle-related outcomes, we found no overt effects of this on
      the exposure-risk associations.

PMID- 18329894
TI  - Gender differences in associations between body mass index and DSM-IV mood and
      anxiety disorders: results from the National Epidemiologic Survey on Alcohol and
      Related Conditions.
AB  - PURPOSE: The purpose of this study is to examine gender differences in
      associations between body mass index (BMI) and affective disorders. METHODS: We
      used logistic regression to examine the effects of BMI and gender on Diagnostic
      and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mood and
      anxiety disorders in a sample of 40,790 adults. RESULTS: Obesity (BMI >30.0) was
      associated with increased risk for any mood disorder, major depressive disorder,
      and dysthymic disorder, in both men and women (odds ratios [ORs], 1.35-1.88).
      Risk of bipolar I and II disorders was elevated in obese women (ORs, 1.70-2.41)
      but not men. Overweight (BMI = 25.0-29.9) predicted increased risk for any mood
      disorder and bipolar I disorder in women but not in men (ORs, 1.16-1.44). Obesity
      was associated with increased odds of any anxiety disorder and specific phobia in
      men and women (ORs, 1.35-1.79). Obese women were additionally at increased risk
      for social phobia. Overweight predicted increased risk of social phobia and
      specific phobia for women but not for men (ORs, 1.27-1.37). CONCLUSIONS: Obese
      individuals of both genders are at increased risk for a range of mood and anxiety
      disorders, but women who are even moderately overweight experience increased
      risks for some disorders as well.

PMID- 18329895
TI  - Availability of gynecologic services in the department of veterans affairs.
AB  - PURPOSE: The optimum approach to providing the Congressionally mandated gender
      specific services for which women veterans are eligible is unknown. We evaluated
      onsite availability of gynecologic services, clinic type and staffing
      arrangements, and the impact of having a gynecology clinic (GYN) and/or an
      obstetrician gynecologist (OBGYN) routinely available. METHODS: We analyzed data
      from the 2001 national VHA Survey of Women Veterans Health Programs and Practices
      (n = 136 sites; response rate, 83%). We assessed availability of gynecologic
      services, and evaluated differences in availability by clinic type (designated
      women's health provider in primary care [PC], separate women's health clinic for
      primary care [WHC], and/or separate GYN) and staffing arrangements (OBGYN
      routinely involved versus not). MAIN FINDINGS: Out of 133 sites, 77 sites (58%)
      offered services through a GYN and 56 sites (42%) did not have GYN. Seventy-two
      (54%) sites had a WHC. More sites with an OBGYN provided endometrial biopsies
      (91% vs. 20%), IUD insertion (85% vs. 14%), infertility evaluation (56% vs. 23%),
      infertility treatment (25% vs. none), gynecologic surgery (65 vs. 28%), p < .01.
      In comparison to sites without WHC, those with WHC were more likely to offer
      services onsite: endometrial biopsy odds ratio (OR) 6.0 (95% confidence interval
      [CI], 2.0-18.1); IUD insertion 4.4 (1.6-12.2); infertility evaluation 2.8 (1.2
      6.3); and gynecologic surgery 2.3 (1.0-5.4). CONCLUSION: As the VA develops
      strategic plans for accommodating the growing number of women veterans, leaders
      should consider focusing on establishing WHC for primary care and routine
      availability of OBGYN or other qualified clinicians, rather than establishing
      separate GYN.

PMID- 18329896
TI  - Cultural and educational disparities in the use of primary and preventive health
      care services among midlife women in Israel.
AB  - PURPOSE: This study aimed to assess rates of primary and preventive healthcare
      use among women in midlife from different cultural origins and to identify
      sociodemographic and health characteristics that could explain cultural
      differences in health care utilization. METHODS: Data were collected for the
      Women's Health in Midlife National Study in Israel, in which women aged 45-64
      were randomly selected according to age and ethnic/origin group strata: Long-term
      Jewish residents (n = 540), immigrants from the former Soviet Union (n = 151),
      and Arab women (n = 123). Interviews included measures of primary and preventive
      visits, clinical screening services (mammogram, Pap smear, bone density), health
      and lifestyle, and sociodemographics. MAIN FINDINGS: Long-term residents reported
      more preventive visits and screening tests and lower use of primary care,
      compared with immigrants and Arab women. In multivariate analyses, cultural
      group, education, self-rated health, and health motivation were significantly
      associated with utilization of primary and preventive care. Ethnic/origin group
      differences were mostly related to cultural differences and not to financial
      barriers or medical factors. For example, among the more traditional group,
      namely, Arab women, low use of preventive gynecologic care seemed to be related
      to the lack of physicians of the same culture and gender. CONCLUSIONS: The
      findings underscore the importance of the primary care physician, especially in
      minority groups, as a provider who can identify at-risk groups and serve as a
      gateway to health promotion. The findings also suggest that the lack of female
      providers may be one explanation for the low utilization of gynecologic services
      among women from traditional cultures.

PMID- 18329897
TI  - Preventive health care among older women in an academic primary care practice.
AB  - PURPOSE: We sought to examine the use of preventive health services among older
      women and to assess how age and illness burden influence care patterns. METHODS:
      The charts of 299 women aged > or =80 and 229 women aged 65-79 years who did not
      have dementia or terminal illness at 1 academic primary care practice in Boston
      were reviewed between July and December 2005 to determine receipt of screening
      tests (e.g., mammography), counseling on healthy lifestyle (e.g., exercise),
      and/or geriatric health issues (e.g., incontinence), and immunizations. Illness
      burden was quantified using the Charlson Comorbidity Index (CCI). RESULTS: Women
      aged > or =80 were more likely than women aged 65-79 to have a CCI of > or =3
      (24.0% vs. 16.7%) and were less likely to receive all screening tests. However,
      receipt of mammography (47.8%) and colon cancer screening (51.2%) was still
      common among women aged > or =80 and was not targeted to older women in good
      health. Women aged > or =80 were less likely to be screened for depression
      (adjusted relative risk [aRR] 0.6; 95% confidence interval [CI], 0.5-0.8),
      osteoporosis (aRR, 0.6; 95% CI, 0.5-0.9), or counseled about exercise (aRR 0.8;
      95% CI, 0.6-0.9) than younger women, but were more likely to receive counseling
      about falls (aRR 1.9; 95% CI, 1.4-2.6) and/or incontinence (aRR 1.8; 95% CI, 1.2
      2.6). However notes documenting discussions about mood (28.6%), exercise (40.0%),
      falls (28.8%), or incontinence (20.8%) were low among all women. CONCLUSION: In a
      comprehensive review of preventive health measures for elderly women, many in
      poor health were screened for cancer. Meanwhile, many older women were not
      screened for depression or counseled about exercise, falls, or incontinence.
      There is a need to improve delivery of preventive health care to older women.

PMID- 18329898
TI  - Relationship of sleep quality with coping and life styles in female Moroccan
      immigrants in Germany.
AB  - BACKGROUND: Epidemiologic studies conducted in Western societies show poorer
      sleep quality in women compared with men. Socioeconomic and stress-related
      psychological variables have been shown to influence sleep, but not much is known
      about sociological and psychological influences on the sleep of women in general
      and non-Western women in particular. The present study reports on
      sociodemographic and coping variables in relation to sleep quality in female
      Moroccan immigrants living in Germany. METHOD: Participants took part in a
      structured personal interview on Pittsburg Sleep Quality Inventory (PSQI) sleep
      quality, coping style preferences, and information related to the degree of
      identification with Western life style. RESULTS: Sleep quality was poor (PSQI >
      6) in 39% of women. Surprisingly, women who had identified with a more Western
      lifestyle had poorer sleep quality than women who had retained their traditional
      Moroccan life style. An unusually large proportion of women preferred monitoring
      (i.e., information-seeking coping style) and adaptive coping (48% and 19%,
      respectively), regardless of sleep quality. Monitoring was more frequent in women
      who were less integrated into German culture. CONCLUSIONS: Results on sleep
      quality suggest that for Moroccan immigrant women in Germany, adopting a Western
      life style may be more stressful than retaining their native life style. The high
      preference for an information seeking approach in coping may reflect the desire
      for information rather than actual coping behavior.

PMID- 18329899
TI  - Study of the viral interference between infectious pancreatic necrosis virus
      (IPNV) and infectious haematopoietic necrosis virus (IHNV) in rainbow trout
      (Oncorhynchus mykiss).
AB  - The resistance of rainbow trout (Oncorhynchus mykiss) to an infectious
      haematopoietic necrosis virus (IHNV) challenge following a preceding non-lethal
      infection with infectious pancreatic necrosis virus (IPNV) was investigated
      through experimental dual infections. Trout initially infected with IPNV were
      inoculated 14 days later with IHNV. Single infections of trout with 1 of the 2
      viruses or with cell culture supernatant were also carried out and constituted
      control groups. No mortality was noted in fish after a single infection with
      IPNV. This virus had no influence on the head kidney leucocyte phagocytic
      activity and plasma haemolytic complement activity. IHNV induced a high mortality
      (72%) and reduced the macrophage phagocytic activity and complement haemolytic
      activity. It also induced a late production of anti-IHNV antibodies which
      occurred after clearance of the virus in the fish. In trout co-infected with both
      viruses, a mortality rate of 2% occurred and the immune parameters were similar
      to those observed in the fish infected with IPNV only, demonstrating that in co
      infected trout IPNV inhibits the effects of IHNV. The studied parameters did not
      allow us to define the mechanism of interference occurring between these 2
      viruses, but some hypothesis are put forward to explain the interference between
      the 2 viruses.

PMID- 18329900
TI  - Biological characterisation of a recombinant Atlantic salmon type I interferon
      synthesized in Escherichia coli.
AB  - Type I (alpha/beta) interferons (IFNs) are a family of cytokines that stimulate
      the expression of numerous proteins that mediate an antiviral state in uninfected
      cells. Two Atlantic salmon (Salmo salar) IFN-alpha (SasaIFN-alpha1 & 2) genes
      have previously been cloned and both were found to contain a putative N-linked
      glycosylation site. Recombinant SasaIFN-alpha1 (rSasaIFN-alpha1) produced in
      eukaryotic systems has repeatedly been shown to confer antiviral properties.
      However, different IFN-alpha subtypes may exhibit differential antiviral
      activities and be subject to glycosylation. To evaluate the potential therapeutic
      impact of a rSasaIFN-alpha, the mature form of the SasaIFN-alpha2 protein was
      produced in a high-level Escherichia coli expression system. Expression of the
      rSasaIFN-alpha2 was detected by SDS-PAGE and Western blot, and its identity was
      confirmed by mass spectrometry. In the homologous Chinook salmon embryonic (CHSE
      214) cell line, the rSasaIFN-alpha2 incited early expression of the IFN-induced
      Mx protein and exhibited high antiviral activity of about 2.8 x 10(6) U mg(-1)
      against infectious pancreatic necrosis virus (IPNV). Conversely, antiviral
      protection by rSasaIFN-alpha2 was not observed in a heterologous Japanese
      flounder embryo (HINAE) cell line. Hence, a biologically active form of rSasaIFN
      alpha2 was successfully produced using a glycosylation-deficient prokaryotic
      system and purified to homogeneity, suggesting that glycosylation is not required
      for its antiviral activity.

PMID- 18329901
TI  - Influence of beta-glucans on the immune responses of carpet shell clam (Ruditapes
      decussatus) and Mediterranean mussel (Mytilus galloprovincialis).
AB  - The effects of beta-glucans on several immune functions of carpet shell clam
      (Ruditapes decussatus) and Mediterranean mussel (Mytilus galloprovincialis)
      hemocytes were determined. Nitric oxide (NO) production increased significantly
      in beta-glucan treated mussels and clams. In mussels, beta-glucans increased by
      themselves the release of free oxygen radicals and also were able to enhance the
      phorbol 12-myristate 13-acetate (PMA) mediated effect on this hemocyte activity.
      However, high doses of beta-glucans when combined with zymosan decreased this
      respiratory burst. In clams, hemolymph treated with several doses of beta-glucans
      limited the growth of the three bacteria, Vibrio algynolyticus (strain TA15),
      Vibrio splendidus (strain TA2) and Escherichia coli (strain ATCC 13706). This
      modulation on the antibacterial activity, however, was not observed when mussel
      hemolymph was incubated with beta-glucans. These results suggest that the immune
      responses of these animals can be up and down modulated by external stimuli and,
      although clams and mussels are both relatively closely related species, their
      behaviour concerning immune responses can be different.

PMID- 18329902
TI  - Cloning and characterization of phospholipase D from olive flounder (Paralichthys
      olivaceus).
AB  - The phospholipase D1 (PLD1) cDNA, designated PoPLD, encoding a predicted protein
      of 1053 amino acids in olive flounder (Paralichthys olivaceus) has been cloned.
      The deduced amino acid sequence shares high identity with that of PLD1s and PLD2
      in human, rat and mouse. The phylogenic analysis and sequence comparison of PoPLD
      with other PLD isozymes were found to be closely related to the PLD1 isozyme in
      primary structure. The tissue expression analysis of PoPLD showed that the mRNA
      of PoPLD was predominantly expressed in the brain, gullet, muscle, stomach, head
      kidney, pyloric caeca, intestine and gill. The expression of the PoPLD gene was
      examined in various tissues of flounder by RT-PCR following stimulation with LPS
      and compared also with that of the inflammatory cytokines IL-1beta and IL-8 in
      various tissues of the stimulated flounder. This provides indirect evidence that
      PLD1 might have a relevant role in immune responses against pathogens and in
      inflammation. In addition, the recombinant protein of PoPLD (GFP-PoPLD), which
      demonstrated a phosphatidylcholine (PC)-hydrolyzing activity, was partially
      localized as a distinct ring-shaped form surrounding the rim of the nucleus in
      EPC cells. Together, our results suggest that PoPLD is similar to the mammalian
      PLD1 isoform, is generally widespread within olive flounder tissue, might have a
      relevant role in the fish immune system against pathogens and specifically may be
      localized in the subcellular membranes of the nuclear rim in EPC cells.

PMID- 18329903
TI  - Variability of haemocyte and haemolymph parameters in European flat oyster Ostrea
      edulis families obtained from brood stocks of different geographical origins and
      relation with infection by the protozoan Bonamia ostreae.
AB  - A research project to compare productive traits (growth and mortality), disease
      susceptibility and immune capability between Ostrea edulis stocks was performed.
      This article reports the results on the immune capability and its relation with
      infection by the intrahaemocytic protozoan Bonamia ostreae. Four to five oyster
      spat families were produced from each of four European flat oyster populations
      (one from Ireland, one from Greece and two from Galicia, Spain) in a hatchery.
      The spat were transferred to a raft in the Ria de Arousa (Galicia) for on growing
      for 2 years. Total haemocyte count (THC) and differential haemocyte count (DHC)
      were estimated monthly through the second year of growing-out. Three types of
      haemocytes were distinguished: granulocytes (GH), large hyalinocytes (LHH) and
      small hyalinocytes (SHH). Significant correlations between the mean relative
      abundance of GH and SHH of the families and the mean prevalence of B. ostreae,
      the overall incidence of pathological conditions and the cumulative mortality of
      the families were found; these correlations supported the hypothesis that high
      %GH and low %SHH would enhance oyster immune ability and, consequently, would
      contribute to lower susceptibility to disease and longer lifespan. Infection by
      B. ostreae involved a significant increase of circulating haemocytes, which
      affected more markedly the LHH type. The higher the infection intensity the
      higher the %LHH. This illustrates the ability of B. ostreae to modulate the
      immune responses of the O. edulis to favour its own multiplication. A significant
      reduction of the phenoloxidase activity in the haemolymph of oysters O. edulis
      infected by B. ostreae was observed. Nineteen enzymatic activities in the
      haemolymph of O. edulis and Crassostrea gigas (used as a B. ostreae resistant
      reference) were measured using the kit api ZYM, Biomerieux. Qualitative and
      quantitative differences in enzyme activities in both haemocyte and plasma
      fractions between B. ostreae noninfected O. edulis from different origins were
      recorded. However, no clear positive association between enzyme activity and
      susceptibility to bonamiosis was found. The only enzyme detected in the resistant
      species C. gigas that was not found in the susceptible one O. edulis was beta
      glucosidase (in plasma). B. ostreae infected O. edulis showed significant
      increase of some enzyme activities and the occurrence of enzymes that were not
      detected in noninfected oysters. These changes could be due to infection-induced
      enzyme synthesis by the host or to enzyme synthesis by the parasite.

PMID- 18329904
TI  - Neural correlates of age-related changes in cortical neurophysiology.
AB  - Functional imaging studies of cortical motor systems in humans have demonstrated
      age-related reorganisation often attributed to anatomical and physiological
      changes. In this study we investigated whether aspects of brain activity during a
      motor task were influenced not only by age, but also by neurophysiological
      parameters of the motor cortex contralateral to the moving hand. Twenty seven
      right-handed volunteers underwent functional magnetic resonance imaging whilst
      performing repetitive isometric right hand grips in which the target force was
      parametrically varied between 15 and 55% of each subject's own maximum grip
      force. For each subject we characterised two orthogonal parameters, B(G) (average
      task-related activity for all hand grips) and B(F) (the degree to which task
      related activity co-varied with peak grip force). We used transcranial magnetic
      stimulation (TMS) to assess task-related changes in interhemispheric inhibition
      from left to right motor cortex (IHIc) and to perform measures relating to left
      motor cortex excitability during activation of the right hand. Firstly, we found
      that B(G) in right (ipsilateral) motor cortex was greater with increasing values
      of age(2) and IHIc. Secondly, B(F) in left ventral premotor cortex was greater in
      older subjects and in those in whom contralateral M1 was less responsive to TMS
      stimulation. In both cases, neurophysiological parameters accounted for
      variability in brain responses over and above that explained by ageing. These
      results indicate that neurophysiological markers may be better indicators of
      biological ageing than chronological age and point towards the mechanisms by
      which reconfiguration of distributed brain networks occurs in the face of
      degenerative changes.

PMID- 18329905
TI  - Distinguishing specific sexual and general emotional effects in fMRI-subcortical
      and cortical arousal during erotic picture viewing.
AB  - Sexual activity involves excitement with high arousal and pleasure as typical
      features of emotions. Brain activations specifically related to erotic feelings
      and those related to general emotional processing are therefore hard to
      disentangle. Using fMRI in 21 healthy subjects (11 males and 10 females), we
      investigated regions that show activations specifically related to the viewing of
      sexually intense pictures while controlling for general emotional arousal (GEA)
      or pleasure. Activations in the ventral striatum and hypothalamus were found to
      be modulated by the stimulus' specific sexual intensity (SSI) while activations
      in the anterior cingulate cortex were associated with an interaction between
      sexual intensity and emotional valence. In contrast, activation in other regions
      like the dorsomedial prefrontal cortex, the mediodorsal thalamus and the amygdala
      was associated only with a general emotional component during sexual arousal. No
      differences were found in these effects when comparing females and males. Our
      findings demonstrate for the first time neural differentiation between emotional
      and sexual components in the neural network underlying sexual arousal.

PMID- 18329906
TI  - The experience of discontinuing antiepileptic drug treatment: an exploratory
      investigation.
AB  - OBJECTIVE: Between 60% and 70% of people with epilepsy become seizure free and
      may choose to withdraw from antiepileptic medication. Numerous studies discuss
      possible factors which may influence seizure recurrence following
      discontinuation. However, few studies attempt to explore the decision-making
      process from the perspective of the patient. It is believed this is the first
      study to explore patients' experience of discontinuing medication following a
      seizure-free period of 2 years. METHOD: Semi-structured interviews were conducted
      with twelve people with epilepsy who had attempted withdrawal from their
      medication. All twelve of the participants lived in the North-East of England. A
      phenomenological approach was taken in order to gain an in depth understanding of
      their withdrawal decisions. RESULTS: Five themes emerged from the interviews.
      Principally, the timing of when to withdraw was a key concern, as well as the
      uncertainty of seizure recurrence, issues with medication and the embarrassment
      of being diagnosed with epilepsy. Those who unsuccessfully withdrew from
      medication discussed their acceptance of the condition. Mixed feelings regarding
      satisfaction with G.P. support were also reported. CONCLUSIONS: Incorporating the
      themes into the Theory of Planned Behaviour [Ajzen I. In: Marks DF, editor. The
      health psychology reader. London: Sage; 1985] provides a model of the withdrawal
      decision-making process based on the experiences of those who have made the
      decision. There is a paucity of research investigating the withdrawal decision,
      therefore the findings from this study should be used for the production of
      appropriate and relevant information regarding the key issues which have been
      raised regarding withdrawal decisions and support those making the decision.

PMID- 18329907
TI  - Frontal lobe epilepsy: clinical characteristics, surgical outcomes and diagnostic
      modalities.
AB  - OBJECTIVE: To identify surgical prognostic factors and to characterize clinical
      features according to the location of the intracranial ictal onset zone of
      frontal lobe epilepsy (FLE) in order to assess the role of various diagnostic
      modalities, including concordances with presurgical evaluations. METHODS: We
      studied 71 FLE patients who underwent epilepsy surgery and whose outcomes were
      followed for more than 2 years. Diagnoses were established by standard
      presurgical evaluation. RESULTS: Clinical manifestations could be categorized
      into six types: initial focal motor (9 patients), initial versive seizure (15),
      frontal lobe complex partial seizure (14), complex partial seizure mimicking
      temporal lobe epilepsy (18), initial tonic elevation of arms (11), and sudden
      secondary generalized tonic-clonic seizure (4). Thirty-seven patients became
      seizure-free after surgery. Five patients were deleted in the analysis because of
      incomplete resection of ictal onset zones. The positive predictive value of
      interictal EEG, ictal EEG, MRI, PET, and ictal SPECT, respectively were 62.5%,
      56.4%, 73.9%, 63.2%, and 63.6%, and the negative predictive value were 46.0%,
      44.4%, 53.5%, 44.7%, and 51.7%. No significant relationship was found between the
      diagnostic accuracy of these modalities and surgical outcome, with the exception
      of MRI (p=0.029). Significant concordance of two or more modalities was observed
      in patients who became seizure-free (p=0.011). We could not find any clinical
      characteristic related to surgical outcome besides seizure frequency. No definite
      relationship was found between the location of intracranial ictal onset zone and
      clinical semiology. CONCLUSION: Although various diagnostic methods can be useful
      in the diagnosis of FLE, only MRI can predict surgical outcome. Concordance
      between presurgical evaluations indicates a better surgical outcome.

PMID- 18329908
TI  - Upper lip nodule.

PMID- 18329909
TI  - Dental extractions related to head and neck radiotherapy: ten-year experience of
      a single institution.
AB  - OBJECTIVE: This study evaluates the frequency of osteoradionecrosis associated
      with dental extractions. STUDY DESIGN: A total of 405 patients submitted to
      radiotherapy and had dental extractions were evaluated. The patients were divided
      into 3 groups. RESULTS: In group 1, 316 patients were submitted to 1.647 dental
      extractions (mean 5.2 teeth per patient) and in another 47 patients the number of
      teeth removed was not clearly reported. Group 2 comprised 5 patients who had 33
      teeth extracted (mean 6.6 each). In group 3, 55 patients had 290 teeth removed
      (mean 5.3 each) and in another 2 patients the number of dental extractions could
      not be established. In general, only 3 cases of osteoradionecrosis related to
      dental extractions were observed: 2 related to exodontias performed before and 1
      after radiotherapy. CONCLUSIONS: The low prevalence of osteoradionecrosis found
      in this work suggests the possibility of performing exodontias after radiotherapy
      by experienced dentists in the management of head and neck cancer.

PMID- 18329910
TI  - Effects of antidepressants and benzodiazepines on stimulated salivary flow rate
      and biochemistry composition of the saliva.
AB  - OBJECTIVES: To evaluate the effect of psychotropics on stimulated salivary flow
      rate (SSFR), total proteins, urea and calcium concentration, alpha-amylase
      activity, pH, saliva buffer capacity (SBC), and the prevalence of xerostomia in
      psychotropic users and its relationship with low SSFR and/or hyposalivation.
      STUDY DESIGN: Thirty-three subjects were allocated to 4 groups: I (control): II
      (psychotropic users); III (subjects of group II using only selective serotonin
      reuptake inhibitors [SSRIs]); and IV (subjects of group II using SSRIs at
      recommended initial dose). The SBC was obtained by titrimetry and salivary
      composition by colorimetric method. RESULTS: Group II presented a significant
      decrease (P = .0203), of 33.85% in SSFR compared with group I. Mean SSFR values
      in groups III and IV showed no significant difference compared with control group
      (P > .05). Xerostomia was observed in 37.50%, 38.46%, and 50% of subjects in
      groups II, III, and IV, respectively. Biochemical composition, pH, and SBC were
      not significantly affected (P > .05) by the use of psychotropics. CONCLUSIONS:
      Xerostomia was associated with a decrease in SSFR and not with alterations in
      biochemical composition. Even when using the latest-generation drugs, there were
      complaints of xerostomia associated with decrease in SSFR.

PMID- 18329911
TI  - Removal of bone plates in patients with maxillofacial trauma: a retrospective
      study.
AB  - OBJECTIVE: The aim of this retrospective study was to assess the incidence of and
      indication for the removal of bone plates over a 5-year period in patients with
      maxillofacial trauma who had received treatment at the Oral and Maxillofacial
      Surgery Unit, Al-Nahda Hospital, Muscat, Oman. STUDY DESIGN: The medical records
      of all patients who underwent removal of bone plates after facial bone trauma
      were reviewed over a 5-year period (2000 to 2004). Data concerning age and gender
      distribution, cause of trauma, year of removal, time between insertion and
      removal, indication for removal, site of removal, and general medical factors
      were evaluated for each patient. RESULTS: Facial bone fractures in 1,177 cases
      were diagnosed during the study period, of which 465 cases underwent open
      reduction and internal fixation using bone plates and screws. In 109 cases bone
      plates were removed (79 males and 30 females), with an overall removal rate of
      23.4%. The most common indication for removal was young age (53.4%) followed by
      infection (25%). The mandible was the most common site of removal (80%). Most of
      the plates (86%) that required removal in adults were removed within the first
      year after insertion. CONCLUSIONS: Based on this study, the incidence of bone
      plate removal was relatively low, and the most common indications for plate
      removal were young age followed by infection.

PMID- 18329912
TI  - Structural effects of sodium hypochlorite solution on RaCe rotary nickel-titanium
      instruments: an atomic force microscopy study.
AB  - OBJECTIVE: The aim of this study was to investigate the effect of sodium
      hypochlorite immersion on the surface characteristics of RaCe rotary nickel
      titanium instruments using atomic force microscopy (AFM). STUDY DESIGN: Four new
      RaCe instruments were used in this study (two 30.06 and two 30.02). One 30.06 and
      one 30.02 instrument were immersed in sodium hypochlorite solution for 5 min.
      Surface topography of the instruments was evaluated using the AFM. The
      instruments were analyzed on 11 points along a 3-mm section. Root mean square
      (RMS) values were used to compare the topographic deviations. The data were
      analyzed using Student t test. RESULTS: Mean RMS values for NaOCl measurements
      were higher than the measurements on new files, and the difference was
      statistically significant (P < .01). CONCLUSION: The AFM results show that NaOCl
      causes deterioration on the surface of RaCe instruments and should be used with
      care during clinical use because of the risk of unexpected failure.

PMID- 18329913
TI  - Relationship between oral health status and development of osteoradionecrosis of
      the mandible: a retrospective longitudinal study.
AB  - OBJECTIVE: Oral health status is a risk factor for postradiation bone
      complications (also known as osteoradionecrosis [ORN]), and oral health care is
      an important element in the prevention of this condition. Some authors recommend
      extracting teeth with a questionable prognosis and either gross mobility or
      periodontal disease. However, the criteria for making such decisions remain to be
      elucidated. In addition, the specific details of the association between oral
      health status and ORN have not yet been clearly demonstrated. The purpose of this
      study was to clarify the relationship between oral health status and the
      development of ORN. STUDY DESIGN: Thirty-nine head and neck cancer patients whose
      radiation fields included both the teeth and the mandible were followed for > or
      = 3 years after radiotherapy. Among these patients, 6 suffered from ORN (ORN
      group), and the other 33 did not experience the condition (non-ORN group). We
      analyzed the patient factors, radiation factors, and oral health factors related
      to the complication. RESULTS: The onset of ORN occurred from 18 months to 51
      months after radiotherapy. The radiation dose in the oral cavity and the oral
      health status before radiotherapy were not significant risk factors for ORN.
      However, the oral health status at 1 year or 2 years after radiotherapy was
      significantly associated with the development of ORN. The oral health conditions
      that increased the risk of ORN were > 5 mm periodontal pocket depth, > 40% dental
      plaque score, > 60% alveolar bone loss level, and a grade 3 radiographic
      periodontal status. CONCLUSION: This is the first report to show the changes in
      the oral health status before and after radiotherapy regarding the development of
      ORN. The results support the periodontal status that almost all clinicians agree
      on as indications for preradiation teeth extraction (namely, periodontal pockets
      of > 5 mm) to prevent ORN. Good oral health status, especially after
      radiotherapy, is very important in the prevention of ORN, and we recommend
      periodical dental management and care by well trained dentists and dental
      hygienists to avoid the condition.

PMID- 18329914
TI  - Antibacterial potential of saliva in children with leukemia.
AB  - OBJECTIVES: The objectives of this study were to evaluate the local oral defense
      mechanisms during the course of leukemia, and to define the correlation between
      the activity of salivary antibacterial factors and the oral clinical findings.
      STUDY DESIGN: A total of 44 children with newly diagnosed acute leukemia
      participated in the study. The control group consisted of 23 healthy children.
      The examination took place at the time of the diagnosis, and during and at the
      end of the chemotherapy treatment course. During the collection of resting mixed
      saliva samples the salivary flow rate was measured. In the saliva's supernatant
      the following parameters were determined: total protein, peroxidase,
      myeloperoxidase, lysozyme, lactoferrin, and secretory immunoglobulin A. RESULTS:
      The introduction of chemotherapy caused a slight decrease of salivary secretion
      rate (P < .05), as well as the decrease of S-IgA concentration (P < .01), which
      remained at the same level after the end of chemotherapy (P < .001). Patients
      with aplasia had decreased levels of peroxidase (P = .014) and myeloperoxidase (P
      = .013). Patients with oral mucositis presented with lower myeloperoxidase (P =
      .026) and peroxidase (P = .003) activity levels as well as the drop of S-IgA (P =
      .000) concentration compared with subjects with no mucositis. CONCLUSIONS:
      Antileukemic treatment contributes to the compromise of salivary defense
      mechanisms, therefore it is reasonable to support pharmacologically the saliva's
      antibacterial potential of leukemic patients to impede the development of local
      infection.

PMID- 18329915
TI  - Sonographic diagnosis of Sjogren syndrome: evaluation of parotid gland
      vascularity as a diagnostic tool.
AB  - OBJECTIVE: To evaluate the usefulness of the vascularity in parotid glands in
      sonographic diagnosis for Sjogren syndrome. STUDY DESIGN: Sonographic images of
      72 cases of previously suspected Sjogren syndrome (including 43 actual cases)
      were analyzed retrospectively for the abnormal vascularity in the parotid gland
      parenchyma. The relationships between the vascularity and the results of
      sialographic, serologic, and histopathologic examinations were analyzed. We also
      compared the diagnostic accuracy of B-mode only with that of B-mode plus Doppler
      mode. RESULTS: Sjogren-positive cases showed significantly higher vascularity. As
      the grade of vascularity became higher, the rate of the Sjogren-negative cases
      became lower. The highest mean vascular score could be observed both in the
      initial stage and in the cavitary-destructive stage in the sialographic grades.
      Sensitivity and accuracy were markedly improved with vascular information.
      CONCLUSION: By using vascular information, sonographic diagnosis for Sjogren
      syndrome can be improved.

PMID- 18329916
TI  - Madelung disease: manifestations of CT and MR imaging.
AB  - OBJECTIVE: The purpose of the present study was to assess the head and neck
      imaging features of Madelung disease on computerized tomography (CT) and magnetic
      resonance imaging (MRI), delineate the effects of the fatty deposits on
      underlying structures, and tabulate the anatomic sites where the neck fat was
      deposited. STUDY DESIGN: Sixteen Chinese patients with Madelung disease in our
      hospital were reviewed. The CT manifestations of the 16 cases and the MRI
      manifestations of 1 case were analyzed retrospectively. The imaging features of
      the fatty distribution in the head and neck area were studied. RESULTS: Cross
      sectional CT showed that the excess fat was symmetric and unencapsulated, mainly
      deposited at the anterior or posterior subcutaneous tissue of the neck, was deep
      under the sternocleidomastoid and trapezius muscles, was situated in the
      posterior cervical triangle, and was around the salivary glands. It was also
      found to be situated in supraclavicular fossa, around the paraspinal muscles and
      larynx, and so on. The accumulated fat at superficial sites was situated at the
      napex and/or at the anterior neck, forming small or large fatty masses to
      protrude backwards locally or sometimes at submentum; the markedly thickened neck
      might appear tubby or oval in anteroposterior diameter. The accumulated fat at
      deep sites compressed adjacent muscles, salivary glands, and great vessels and
      caused them to shift and deform. The distinctive appearance was that marked
      thickening of fat caused sternocleidomastoid muscles and submaxillary glands to
      shift forward obviously, like a bird spreading its wings. The density of the
      abnormally proliferated fat was equal to that of normal fat. In MRI, the
      distribution of the excess fat was equal to that seen with CT. The signal
      intensity of the excess fat was equal to that of normal fat. Besides the
      accumulation of the neck fat tissue, CT and MRI did not show other abnormal soft
      tissue masses. CONCLUSIONS: The use of CT and MRI can accurately show the excess
      fat based on density of CT and signal intensity of MRI. The density and signal
      intensity of the excess fat are equal to those of normal fat. The excess fat,
      mainly deposited at the anterior or posterior subcutaneous tissue of the neck,
      was deep under the sternocleidomastoid and trapezius muscles, was situated in the
      posterior cervical triangle, and was around the salivary gland, and so on. CT and
      MRI can also show compression, shift, and deformation of surrounding salivary
      glands, great vessels, and muscles caused by the excess fat. The CT and MRI can
      accurately diagnose the disease and exclude other soft tissue tumors.

PMID- 18329917
TI  - Nutritional and management strategies for the prevention of fatty liver in dairy
      cattle.
AB  - Fatty liver occurs in dairy cattle during periods of elevated blood non
      esterified fatty acids (NEFAs). Elevated blood NEFAs are associated with hormonal
      changes at parturition and negative energy balance. Approaches for preventing
      fatty liver include inhibition of fatty acid mobilization from adipose tissues
      and altering hepatic metabolism to enhance fatty acid oxidation or export as a
      constituent of very low-density lipoproteins (VLDL). Nutritional and management
      strategies to implement these approaches have been examined. Increasing energy
      density of diet, either by increasing non-fiber carbohydrate or fat, has failed
      to prevent fatty liver. Two nutritional supplements, ruminally-protected choline
      and propylene glycol, have proven effective at preventing fatty liver. Choline
      probably enhances hepatic VLDL secretion. Propylene glycol most likely reduces
      fatty acid mobilization from adipose tissue. Shortening or eliminating the dry
      period is a management strategy that reduces the magnitude of negative energy
      balance after calving and triglyceride accumulation in the liver.

PMID- 18329918
TI  - Subacute ruminal acidosis in dairy cows: the physiological causes, incidence and
      consequences.
AB  - During subacute ruminal acidosis (SARA) rumen pH is depressed for several hours
      per day due to accumulation of volatile fatty acids and insufficient rumen
      buffering. Surveys suggested an incidence of SARA of between 19% and 26% in early
      and mid-lactation dairy cows. Causes of SARA include feeding excessive amounts of
      non-structural carbohydrates and highly fermentable forages, and insufficient
      dietary coarse fiber. Consequences of SARA include feed intake depression,
      reduced fiber digestion, milk fat depression, diarrhea, laminitis, liver
      abscesses, increased production of bacterial endotoxin and inflammation
      characterized by increases in acute phase proteins. The increase in endotoxin is
      similar among methods for SARA induction, but depends on the diet fed before
      induction. Increases in acute phase proteins vary among methods of SARA
      induction, even when the methods result in similar rumen pH depressions. This
      suggests that the inflammatory response might not be solely due to bacterial
      endotoxin in the rumen.

PMID- 18329919
TI  - High temperature mechanical field-cycling setup.
AB  - A new design of a mechanical field-cycling setup, operating in the wide
      temperature range up to 1200 K has been implemented. The sample is moved by a
      stepping motor in the stray field of a superconducting magnet inside a furnace of
      homogeneous temperature profile. For a field range from 0.75 to 7 T (transfer
      length 24 cm), the transfer time is less than 100 ms. The temperature profile is
      homogenized to better than 1% of the absolute set temperature. The main objective
      of this design is to extend the T1 relaxation dispersion range covered by
      electronic field-cycling to higher frequencies.

PMID- 18329920
TI  - Indirect determination of chemical shift by coupling evolution during adiabatic
      pulses.
AB  - The use of adiabatic 180 degrees X-pulses within INEPT refocusing periods results
      in chemical shift-dependent evolution of J-couplings. This has been viewed as a
      disadvantage and several methods of overcoming it have been suggested. This
      article shows that there is the potential to use this chemical shift dependence
      to determine heteronuclear chemical shift without a heteronuclear evolution time.
      In this way, it possible to estimate heteronuclear chemical shift indirectly from
      a single one-dimensional proton-observe spectrum and determine it with high
      accuracy from a extensively-folded two-dimensional proton-observe spectrum.

PMID- 18329921
TI  - The correlation between headache and refractive errors.
AB  - PURPOSE: To compare the prevalence of refractive errors in patients with headache
      and a control population. METHODS: Three hundred ten patients with headache and
      843 controls were retrospectively evaluated. Complete ophthalmologic examination
      was performed in the headache group. Autorefraction was performed in all
      participants (with cycloplegia under 10 years of age). Myopia was defined as the
      spherical equivalent refraction of at least -0.50 D, hyperopia as the spherical
      equivalent refraction of at least +2.0 D, and astigmatism as the cylinder of at
      least 1.0 D. Main outcome measures were refractive error, anisometropia, and
      previous miscorrection of refractive error. Chi-square and Student's t-tests were
      used for statistical analysis. RESULTS: Total prevalence of refractive errors was
      higher in the headache group (p = 0.002). The rate of astigmatism was higher in
      the headache group (p < 0.0001), while that of myopia and hyperopia were similar
      in both groups (p = 0.74, p = 0.79, respectively). The rates of compound and
      mixed astigmatism were higher in the headache group (p = 0.026, p < 0.001,
      respectively). The rates of anisometropia and previous miscorrection of
      refractive error were higher in the headache group (p < 0.0001 for both).
      Children with headache have a statistically significant increased risk of total
      refractive errors (OR = 1.57, 95% CI: 1.18-2.07), anisometropia (OR = 9.59, 95%
      CI: 5.72-16.1), and miscorrection of refractive error (OR = 9.57, 95% CI: 5.43
      16.9). CONCLUSIONS: Compound and mixed types of astigmatism, anisometropia, and
      miscorrection of refractive error were found more often in patients with headache
      than in control subjects.

PMID- 18329922
TI  - Results of extraocular muscle surgery in WEBINO bilateral internuclear
      ophthalmoplegia patients.
AB  - PURPOSE: To evaluate the results of extraocular surgery in patients with large
      exotropias from "wall-eyed" bilateral internuclear ophthalmoplegia (WEBINO).
      METHODS: Eight patients with WEBINO evaluated between November 1994 and October
      2006 underwent extraocular muscle surgery. Three patients required a second
      procedure. RESULTS: An 85% reduction in exodeviation occurred postoperatively.
      Fusion responses were demonstrable in 87.5% of patients. Other ocular signs of
      internuclear ophthalmoplegia (INO) such as adduction limitation, abducting
      nystagmus, and ocular dysmetria also improved. These results were obtained
      following two-staged unilateral recession-resection procedures in seven patients;
      the remaining patient underwent bilateral lateral rectus recessions. CONCLUSIONS:
      Binocular outcomes are achievable in patients with WEBINO following extraocular
      muscle surgery, and associated ocular signs may be reduced or eliminated.

PMID- 18329923
TI  - Implantation of the Artisan iris reconstruction intraocular lens in 5 children
      with aphakia and partial aniridia caused by perforating ocular trauma.
AB  - PURPOSE: To describe the long-term clinical results of the implantation of the
      Artisan iris reconstruction IOL in 5 eyes of 5 children for aphakia and partial
      aniridia attributable to penetrating ocular trauma. METHODS: The charts of 5
      children were retrospectively reviewed. The nature and the extent of injury; age
      at IOL implantation; visual, refractive, and cosmetic outcome; endothelial cell
      density; and complications and subsequent surgical interventions were evaluated.
      RESULTS: Mean follow-up period was 8.9 years (range, 4.9-12.4). Mean age at
      implantation of the Artisan iris reconstruction IOL was 9.5 years (range, 7.7
      12.7). Visual acuity improved in 2 of 5 eyes, remained stable in 2 of 5 eyes, and
      decreased in 1 of 5 eyes. Complaints of photophobia were reduced, and a
      satisfactory cosmetic outcome was achieved in 3 of 5 patients. The mean spherical
      equivalent refraction error at last follow-up was -4.0 D. Mean endothelial cell
      loss when compared with the healthy fellow eye was 42%. Two cases were
      complicated by partial luxation of the IOL, one case by persistent anterior
      uveitis and secondary glaucoma. One eye developed a retinal detachment.
      CONCLUSIONS: The Artisan iris reconstruction IOL is a treatment option for the
      treatment of aniridia and aphakia due to penetrating ocular trauma in children.
      We emphasize the high-risk characteristics of the eyes treated and the importance
      of careful patient selection in the outcome of the implantation of the Artisan
      iris reconstruction IOL.

PMID- 18329924
TI  - Diagnosis of Factor XI deficiency following congenital cataract extraction.
AB  - Factor XI deficiency is a rare coagulopathy that requires a specific approach to
      preoperative planning. Herein we report a case where ophthalmic surgery led to
      this diagnosis in a 4-month old boy and review the warranted prophylactic
      measures prior to operative intervention.

PMID- 18329925
TI  - Agreement among pediatric ophthalmologists in diagnosing plus and pre-plus
      disease in retinopathy of prematurity.
AB  - PURPOSE: Plus disease has become the major criterion for laser treatment in
      infants with retinopathy of prematurity (ROP), but its assessment is subjective.
      Our purpose was to compare quadrant-level and eye-level assessment of plus
      disease and pre-plus disease among 3 experienced ROP examiners and to report
      their rate of agreement. METHODS: One hundred eighty-one high-quality RetCam
      images from premature infants were graded by 3 of the authors. Dilation and
      tortuosity were judged separately using a scale of normal or sufficiently
      abnormal to meet criteria for pre-plus or plus disease. RESULTS: There was
      disagreement on the presence of plus disease for 18 images (10%), on tortuosity
      sufficient for plus disease (plus tortuosity) for 26 images (14%), and on
      dilation sufficient for plus disease (plus dilation) for 26 images (14%). Of 67
      images judged to have pre-plus disease or worse, there was disagreement on the
      presence of plus disease for 18 images (27%), on plus tortuosity for 25 images
      (37%), and on plus dilation for 21 images (31%). For distinguishing plus or pre
      plus disease from normal, there was disagreement on pre-plus tortuosity for 38 of
      181 images (21%) and on pre-plus dilation for 58 of 181 images (32%).
      CONCLUSIONS: Three experienced ROP examiners disagreed frequently on the
      diagnosis of plus or pre-plus disease when evaluating cropped clinical
      photographs of infants, many of which had borderline plus disease. Further study
      is required to determine the implications of these observations on clinical
      decision making.

PMID- 18329927
TI  - Dissociated vertical deviation in patients with intermittent exotropia.
AB  - PURPOSE: To determine whether the age of strabismus onset and the degree of
      stereopsis are related to the development of dissociated vertical deviation (DVD)
      in patients with intermittent exotropia and to describe the characteristics of
      DVD in patients with intermittent exotropia and DVD. METHODS: Retrospective
      record review of patients with (1) intermittent exotropia with DVD; (2) infantile
      esotropia with DVD; and (3) intermittent exotropia without DVD. Age of strabismus
      onset, stereopsis, strabismus measurements, and the response of DVD to the
      Bielschowsky head-tilt test were compared among the three groups. RESULTS: Fifty
      two children with intermittent exotropia and DVD were identified. In patients
      with intermittent exotropia with DVD and intermittent exotropia without DVD
      group, the mean age of strabismus onset was 12.7 months and 28.9 months,
      respectively (p = 0.03), and mean stereopsis was 147 arcsec and 65 arcsec (p =
      0.02). In patients with intermittent exotropia with DVD and infantile esotropia
      with DVD, the mean amount of DVD was 9.7(Delta) and 17.2(Delta), respectively (p
      < 0.01). Bielschowsky head-tilt test showed an increase of DVD on ipsilateral
      head tilt in 91% and 63.3%, respectively. CONCLUSIONS: Intermittent exotropia
      with DVD is characterized by earlier onset of strabismus and worse stereopsis,
      suggesting that these factors may be related to the development of DVD in
      patients with intermittent exotropia. Unlike DVD in infantile esotropia, DVD in
      intermittent exotropia was smaller in amount and demonstrated a more uniform
      response to the Bielschowsky head-tilt test.

PMID- 18329928
TI  - Evaluation of vertical rectus muscles using ultrasound biomicroscopy.
AB  - PURPOSE: To evaluate the accuracy of ultrasound biomicroscopy (UBM) in measuring
      the distance (in mm) from limbus to the insertion of vertical rectus muscles
      (superior rectus and inferior rectus compared with the "gold standard" surgical
      caliper at the time of surgery. METHODS: Prospective, masked, observational study
      of 31 vertical rectus muscle insertions in which we compared the measurements
      from the limbus as measured by 50 MHz UBM, either preoperatively or at the time
      of anesthesia, with that measured by surgical caliper intraoperatively.
      Measurements (UBM and surgical) were evaluated by two different observers and
      analyzed using the Bland-Altman method. All UBM measurements were done by the
      same author. The intraclass correlation coefficient (ICC) and Pearson coefficient
      with 95% confidence intervals were used to quantify the degree of agreement
      between the two methods. RESULTS: Thirty-one vertical muscles were evaluated (13
      superior rectus and 18 inferior rectus, of which 7 muscles were reoperations).
      The average for UBM measurements was 6.63 mm and for surgical caliper was 7.09
      mm. The measurements for the two methods were all within +/-2 standard deviations
      of the mean. Only three measurements showed differences more than 1 mm. The ICC
      was 0.78 and Pearson coefficient was 0.85, indicating a "very good" correlation
      between the two methods. The longest distance from the limbus that could be
      accurately measured with the UBM was 12 mm. In one case a pseudotendon was
      differentiated from the true insertion of a previously recessed superior rectus
      muscle. CONCLUSIONS: The UBM and surgical measurements showed "very good"
      correlation when allowing for a margin of error of +/-1.0 mm between the two
      modalities, indicating that the UBM is a good predictor of the position of the
      vertical rectus muscles.

PMID- 18329929
TI  - Oculomotor abnormalities in a patient with fragile X-associated tremor/ataxia
      syndrome.
AB  - We present a case report of an 80-year-old man with Fragile X-associated
      tremor/ataxia syndrome (FXTAS) and acquired diplopia, strabismus, and other
      oculomotor abnormalities. This is the first case report of ocular abnormalities
      in a patient with FXTAS.

PMID- 18329930
TI  - Infantile corneal myxoma.
AB  - Myxomas, benign tumors of modified fibroblasts that produce small amounts of
      collagen but large amounts of glycosaminoglycans, typically occur in the left
      atrium of the heart or various soft tissues. Corneal myxoma is extremely rare,
      with only 8 previously reported cases to date, all of which were in individuals
      26 years of age or older. The current report documents the clinical and
      histopathologic features of a 4-month-old girl with infantile corneal myxoma.

PMID- 18329931
TI  - Sequential leukemic infiltration and human herpesvirus optic neuropathy in acute
      lymphoblastic leukemia.
AB  - Leukemic infiltration is a common cause of optic disk swelling in a patient with
      acute lymphoblastic leukemia (ALL). Recurrence of optic disk swelling in a
      patient with previous leukemic infiltration carries a grave prognosis when it is
      associated with recurrent central nervous system disease. We report a case of
      recurrent swelling of an optic disk in a patient with T-cell ALL who had
      previously been treated for CNS relapse with optic nerve involvement. In this
      case the swelling was associated with cytomegalovirus infection and resolved
      following treatment with antiviral therapy.

PMID- 18329932
TI  - Canine models of asthma and COPD.
AB  - Dogs have been extensively used to model the important components of asthma and
      COPD. Many of the key features of human asthma such as reversible airflow
      obstruction, pulmonary inflammation, airway hyperresponsiveness and cough are
      demonstrated in dogs after provocation with antigen, following a period of
      hyperventilation with dry air or after inhalation of ozone. Furthermore, standard
      anti-asthma drugs such as beta-adrenergic agonists, corticosteroids and
      leukotriene inhibitors are effective in these models. The pathology and
      pathophysiology of chronic bronchitis and emphysema can also be demonstrated in
      dogs after exposure to cigarette smoke, following inhalation of sulfur dioxide
      and by intra-tracheal or aerosol administration of proteolytic enzymes such as
      papain. These canine models of COPD have been used to evaluate a variety of new
      methodologies and treatments before they are tested in humans. This review
      highlights some of the important features of these canine models and how they
      have increased our understanding of the pathology, pathophysiology and control of
      human asthma and COPD.

PMID- 18329933
TI  - Modulation of digestive enzyme activities during ontogeny of Labeo rohita larvae
      fed ascorbic acid enriched zooplankton.
AB  - The effect of supplementation of ascorbic acid through enriched zooplankton [10%,
      20% and 30% ascorbyl palmitate (AP) inclusion in diet of zooplankton] on
      different digestive enzyme activities during ontogeny of Labeo rohita larvae was
      studied from 4 day to 15 day post hatch. Ascorbic acid (AA) content in different
      groups of unenriched (8.6+/-0.71) and enriched zooplankton were, 750+/-29.3,
      1409.1+/-45.5, 2009.21+/-199.2 mug/g respectively on dry matter basis with
      differences (P<0.05) between the treatments. A difference (P<0.05) was found in
      tissue AA level in different dietary groups. Low amylase, protease, lipase and
      alkaline phosphatase activities were present in rohu larvae from the mouth
      opening stage which showed increasing trend with the age of larvae and increasing
      dietary AA content. A clear dose-dependent modulation of digestive enzyme
      activities in response to 10%, 20% and 30% AP enriched zooplankton feeding was
      evidenced from positive correlations between dietary AA content with magnitude of
      elevation of enzyme activity in different groups. There were 57, 55, 29.2 and 2
      fold increases in amylase activity; 7.35, 7.02, 4.43 and 2.73 fold increases in
      protease activity; 45.636, 41.50, 19.83 and 13.69 fold increases in lipase
      activity and 6, 5, 3, and 2 fold increases in alkaline phosphatase activity
      observed in the 15th day post hatch larvae fed 20%, 30%, 10%AP enriched and
      normal zooplankton respectively, than 4-day post hatch larvae of the respective
      groups. Enzyme activities were also positively correlated with specific growth
      rates of wet weight of rohu larvae at the 15th day post hatch. Increased AA might
      have played an important role in advancing morphological transformation of the
      digestive tract, protecting gastric mucosa and accelerating growth by the process
      of tissue formation, which necessitated the requirement of more nutrient thereby,
      increasing digestive enzyme activity. The regulatory role of AA in the modulation
      of different digestive enzymes activity and its physiological consequences of
      nutrient digestibility and utilization during ontogenesis could be extrapolated
      for better nutrient management of the larvae.

PMID- 18329934
TI  - Lethal hepatopathy and leukodystrophy caused by a novel mutation in MPV17 gene:
      description of an alternative MPV17 spliced form.
AB  - It has recently been reported that mutations in MPV17 gene may be causative of
      mtDNA depletion syndrome (MDS). Patients with this alteration presented with
      severe liver failure, hypoglycemia, growth retardation and neurological symptoms
      during the first year of life. We report on the clinical, biochemical and
      molecular findings of a patient presenting with lethal hepatopathy,
      polyneuropathy, neurological regression and leukodystrophy associated with
      mutations in MPV17. Mitochondrial respiratory chain activities were low in liver
      and within reference values in muscle. However, levels of mtDNA were markedly
      reduced both in muscle and liver. A novel homozygous mutation in MPV17, c.70+5G>A
      (IVS1+5G>A), was identified. This intronic change causes the full-length cDNA
      loss, probably due to loss of strength of the splice donor site of exon 1.
      Western blot analysis, performed in liver homogenates, further corroborates these
      results as the amount of patient's protein was highly reduced, or almost absent,
      compared with that of controls. We also identified an additional alternative
      spliced form in controls and in the patient, due to exon 2 skipping, that has not
      previously been reported.

PMID- 18329935
TI  - Onset or exacerbation of cutaneous psoriasis during TNFalpha antagonist therapy.
AB  - The widespread use of TNFalpha antagonists in recent years has led to the
      recognition of paradoxical adverse effects, defined as the onset or exacerbation
      of disorders that are usually improved by TNFalpha antagonists. Cutaneous
      psoriasis is an example, of which several cases have been reported. OBJECTIVE: To
      identify cases of psoriasis onset or exacerbation during TNFalpha antagonist
      therapy and to look for potential predictive factors. METHODS: We retrospectively
      reviewed cases of psoriasis onset or exacerbation during TNFalpha antagonist
      therapy. For each case we recorded the following data: age, sex, underlying
      disease, nature of the TNFalpha antagonist, effectiveness in improving the
      underlying disease, history of psoriasis in the patient or family, time to
      psoriasis development, type of psoriasis (confirmed by an experienced
      dermatologist), concomitant treatments, whether the TNFalpha antagonist was
      stopped or continued, and the outcome of the psoriasis. These data were compared
      to those in the literature. RESULTS: We identified 12 patients, six men and six
      women, with a mean age of 45.5 years. The TNFalpha antagonist was adalimumab in
      four patients, etanercept in six patients, and infliximab in two patients. The
      underlying disease was ankylosing spondylitis in six cases, rheumatoid arthritis
      in four, and psoriatic arthritis in two. Mean time from treatment initiation to
      psoriasis was 4.1 months (range, 1-15 months). A previous history of psoriasis in
      the patient was noted in six cases, including four of the six patients taking
      etanercept. TNFalpha antagonist therapy was effective on the underlying disease
      in 11 of the 12 patients. The drug was discontinued in five patients, of whom
      four experienced resolution of their psoriasis. In the remaining seven patients,
      the drug was continued and the skin lesions remained unchanged. Most of the
      patients had psoriasis vulgaris (plaque psoriasis); palmoplantar pustulosis was a
      feature in five patients. DISCUSSION: Over 40 cases of psoriasis onset or
      exacerbation during TNFalpha antagonist therapy have been reported in the
      literature. The prevalence of this adverse effect has been estimated at 1.5-5% of
      patients taking TNFalpha antagonists. The findings from our case series are
      consistent with data in the literature. Psoriasis is a class effect that has been
      reported with all the currently available TNFalpha antagonists. The skin lesions
      develop within the first few months of therapy. Patients with a wide range of
      underlying diseases can be affected. Palmoplantar pustulosis is a common feature.
      A previous history of psoriasis seems more common in patients who experience
      psoriasis onset or exacerbation during etanercept therapy (four of six patients
      in our study and 55% in the literature); thus, previous psoriasis may be a risk
      factor for psoriasis exacerbation during etanercept therapy.

PMID- 18329936
TI  - Septic arthritis of the hip with Propionibacterium avidum bacteremia after
      intraarticular treatment for hip osteoarthritis.
AB  - Propionibacterium avidum is a Gram-positive, nonsporulating, facultative anaerobe
      that has a low level of virulence and is rarely pathogenic. This ubiquitous
      inhabitant of the sebaceous glands and hair follicles can cause acne vulgaris.
      Very rarely, P. avidum causes systemic infections after invasive procedures, most
      notably in immunocompromised patients. Two cases of sacroiliitis due to P. avidum
      have been reported. We report a case of P. avidum arthritis of the hip with
      severe sepsis that developed in a 78-year-old woman after intraarticular
      glucocorticoid treatment for hip osteoarthritis. We are unaware of previous
      reports of P. avidum hip arthritis.

PMID- 18329937
TI  - [Tocolysis in premature rupture of membranes: prescription or prohibition?].

PMID- 18329938
TI  - Population genetic data for 15 STR loci (Identifiler kit) in Honduras.
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 198 unrelated individuals from Honduras,
      Central America.

PMID- 18329939
TI  - An autopsy case of commotio cordis from a motor scooter accident.
AB  - A motor scooter carrying two 15-year-old boys collided with the back of an open,
      parked truck. The tailgate of the truck was down and in a horizontal position. At
      the autopsy of the driver, horizontal tramline bruises were found on the anterior
      chest, but the thoracic cage was intact. There was a transverse tear of the
      ascending aorta with adventitial hematoma, but significant bleeding was not found
      in the pericardial sac or the thoracic cavities. Therefore, it was obvious that
      cardiovascular collapse occurred immediately after the accident. Neither injuries
      nor diseases that would cause the instantaneous death were found on examination
      of the whole body. We determined that the driver died of commotio cordis due to
      blunt force to the anterior chest.

PMID- 18329940
TI  - A finite element model to accurately predict real deformations of the breast.
AB  - Most surgical procedures in breast plastic surgery are either reconstructive
      procedures following oncologic interventions (tumorectomy, quadrantectomy,
      mastectomy ...) or aesthetic ones, both augmentation and reduction. With current
      techniques, the results of such procedures cannot be fully guaranteed. Usually,
      surgical planning is based on a photographic and anthropometric study of the
      breast only. Among others, one of the difficulties that the plastic surgeons have
      is the noticeable change of the breast shape with the position of the patient.
      Thus, it is more and more necessary to plan a presurgical methodology to help the
      plastic surgeon and guarantee the patient a successful result of the
      intervention. In order to establish a reliable simulation method that could
      predict a patient-specific outcome after breast surgery, this study started
      trying to correlate spatial features of the breast between lying and standing up
      positions. A biomechanical model of breast was proposed and implemented into a
      finite element context to predict deformations, and from these the breast shape
      in different positions. The resulting shapes were compared with multimodal
      images, whereas the breast surface displacements were compared with manually
      identified landmarks and 3D scanner images. From the results, it can be concluded
      that the model hereby presented reasonably approximates breast response to
      gravity forces, therefore providing accurate and useful information to the
      surgeon planning such surgical procedures.

PMID- 18329941
TI  - Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson's
      disease is related to disability of the patients.
AB  - We investigated neuronal number and size in the pars compacta of the
      pedunculopontine nucleus (PPN) in Parkinson's disease (PD). In PD, the number of
      Luxol fast blue (LFB) neurons was reduced by 27% from the mean control value
      (p=0.04) and the cholinergic (choline acetyltransferase, ChAT-positive) neuron
      number was reduced by 36% (p=0.03). In addition to neuronal loss, the remaining
      neurons in the PPN in PD were smaller than in controls. The profile area of LFB
      neurons was reduced by 14% (p=0.009) and that of ChAT-positive neurons by 26%
      (p=0.001). There was more severe loss of ChAT-positive neurons with a more severe
      stage of the disease, evaluated by the modified Hoehn and Yahr scale (r=-0.66,
      p=0.03). The neuron number decreased much more than could be expected on the
      basis of decrease in cell size alone.

PMID- 18329942
TI  - A diagnostic challenge of Parkinson's disease: intractable hiccups.
AB  - Parkinson's disease is a common neurodegenerative disorder and the diagnosis
      depends mostly on clinical assessment so it is important to be aware of less
      common symptoms of the disease for correct diagnosis and therapy. We describe a
      patient with intractable hiccups as a very unusual presentation of Parkinson's
      disease.

PMID- 18329943
TI  - Interobserver reliability of physical examination of shoulder girdle.
AB  - The object of this study was to assess interobserver reliability in 23 tests
      concerning physical examination of the shoulder girdle. A physical therapist and
      a physical therapist/manual therapist independently performed a physical
      examination of the shoulder girdle in 91 patients with shoulder complaints of
      varying severity and duration. The observers assessed 23 items in total: active
      and passive abductions, passive external rotation, hand in neck (HIN) test, hand
      in back (HIB) test, impingement test according to Neer, springing test of the
      first rib and joint play test of the acromioclavicular joint. The interobserver
      reliability was evaluated by means of a Cohen's Kappa, the weighted Kappa and the
      intraclass correlation (ICC). Criteria for acceptable reliability were: Kappa
      value>or=0.60, ICC>or=0.75 or an absolute agreement>or=80%. The results showed
      that Kappa values varied from 0.09 (springing test first rib, stiffness) to 0.66
      (springing test first rib, pain), weighted Kappa varied from 0.35 (pain during
      HIB) to 0.73 (range of motion HIB) and ICC varied from 0.54 (abduction passive
      starting point painful arc) to 0.96 (active and passive ranges of motion in
      abduction). In total 11 (48%) items fulfilled the criteria of acceptable
      reliability. In conclusion, there appears to be a great deal of variation in the
      reliability of the tests used in the physical examination of the shoulder girdle.
      Over 50% of the tests did not meet the statistical criteria for acceptable
      reliability.

PMID- 18329944
TI  - Apoptosis signalling is essential and precedes protein degradation in wasting
      skeletal muscle during catabolic conditions.
AB  - Activation of skeletal muscle proteolysis leads to wasting in many types of
      catabolic/chronic diseases. Protein breakdown is basically accomplished by the
      activation of the ubiquitin-proteasome system. Interestingly, several
      publications have shown that DNA fragmentation also occurs in skeletal muscle
      tissue during catabolism. The present review suggests that activation of
      apoptosis precedes protein breakdown associated with muscle wasting. In addition,
      the role of the different proteolytic systems and their relation with apoptosis
      is emphasized. Altogether, the data presented could be used for the design of new
      approaches for the treatment of muscle wasting diseases.

PMID- 18329946
TI  - Misincorporation of amino acid analogues into proteins by biosynthesis.
AB  - Despite astounding diversity in their structure and function, proteins are
      constructed from 22 protein or 'canonical' amino acids. Hundreds of amino acid
      analogues exist; many occur naturally in plants, some are synthetically produced
      or can be produced in vivo by oxidation of amino acid side-chains. Certain
      structural analogues of the protein amino acids can escape detection by the
      cellular machinery for protein synthesis and become misincorporated into the
      growing polypeptide chain of proteins to generate non-native proteins. In this
      review we seek to provide a comprehensive overview of the current knowledge on
      the biosynthetic incorporation of amino acid analogues into proteins by mammalian
      cells. We highlight factors influencing their incorporation and how the non
      native proteins generated can alter cell function. We examine the ability of
      amino acid analogues, representing those commonly found in damaged proteins in
      pathological tissues, to be misincorporated into proteins by cells in vitro,
      providing us with a useful tool in the laboratory to generate modified proteins
      representing those present in a wide-range of pathologies. We also discuss the
      evidence for amino acid analogue incorporation in vivo and its association with
      autoimmune symptoms. We confine the review to studies in which the synthetic
      machinery of cell has not been modified to accept non-protein amino acids.

PMID- 18329945
TI  - Leukocyte cell surface proteinases: regulation of expression, functions, and
      mechanisms of surface localization.
AB  - A number of proteinases are expressed on the surface of leukocytes including
      members of the serine, metallo-, and cysteine proteinase superfamilies. Some
      proteinases are anchored to the plasma membrane of leukocytes by a transmembrane
      domain or a glycosyl phosphatidyl inositol (GPI) anchor. Other proteinases bind
      with high affinity to classical receptors, or with lower affinity to integrins,
      proteoglycans, or other leukocyte surface molecules. Leukocyte surface levels of
      proteinases are regulated by: (1) cytokines, chemokines, bacterial products, and
      growth factors which stimulate synthesis and/or release of proteinases by cells;
      (2) the availability of surface binding sites for proteinases; and/or (3)
      internalization or shedding of surface-bound proteinases. The binding of
      proteinases to leukocyte surfaces serves many functions including: (1)
      concentrating the activity of proteinases to the immediate pericellular
      environment; (2) facilitating pro-enzyme activation; (3) increasing proteinase
      stability and retention in the extracellular space; (4) regulating leukocyte
      function by proteinases signaling through cell surface binding sites or other
      surface proteins; and (5) protecting proteinases from inhibition by extracellular
      proteinase inhibitors. There is strong evidence that membrane-associated
      proteinases on leukocytes play critical roles in wound healing, inflammation,
      extracellular matrix remodeling, fibrinolysis, and coagulation. This review will
      outline the biology of membrane-associated proteinases expressed by leukocytes
      and their roles in physiologic and pathologic processes.

PMID- 18329947
TI  - Aberrant AID expression and human cancer development.
AB  - Cancer develops via a multistep process that occurs through the accumulation of
      somatic mutations of tumor-related genes that govern cell proliferation,
      regeneration, and apoptosis. The question how normal cells acquire the genetic
      changes that lead to malignant transformation is, however, unknown at present.
      Activation-induced cytidine deaminase (AID) produces immune-diversity by inducing
      somatic hypermutations and class-switch recombinations in human immunoglobulin
      genes. Unfortunately, this function of AID as a genome mutator could aim at the
      generation of somatic mutations in various host genes of non-lymphoid tissues and
      contribute to tumorgenesis. Notably, aberrant AID expression can be triggered by
      several pathogenic factors, including Helicobacter pylori infection and
      proinflammatory cytokine stimulation, in human epithelial cells, whereas AID
      expression is absent in those cells under physiologic conditions. Thus, aberrant
      AID activity in epithelial tissues may provide the critical link between
      inflammation, somatic mutations, and cancer development.

PMID- 18329948
TI  - A central circuit of the mind.
AB  - The methodologies of cognitive architectures and functional magnetic resonance
      imaging can mutually inform each other. For example, four modules of the ACT-R
      (adaptive control of thought - rational) cognitive architecture have been
      associated with four brain regions that are active in complex tasks. Activity in
      a lateral inferior prefrontal region reflects retrieval of information in a
      declarative module; activity in a posterior parietal region reflects changes to
      problem representations in an imaginal module; activity in the anterior cingulate
      cortex reflects the updates of control information in a goal module; and activity
      in the caudate nucleus reflects execution of productions in a procedural module.
      Differential patterns of activation in such central regions can reveal the time
      course of different components of complex cognition.

PMID- 18329949
TI  - Assessment of problems with appearance, following surgery for oral and oro
      pharyngeal cancer using the University of Washington appearance domain and the
      Derriford appearance scale.
AB  - The first aim of this study was to describe appearance issues in patients
      following surgery for oral and oro-pharyngeal squamous cell carcinoma using the
      Derriford appearance scale (DAS24) and the University of Washington Quality of
      Life Questionnaire Version 4 appearance item (UWQOL v4). Another aim was to
      compare these two questionnaires and justify a cut-off in the UWQOL. Also the
      study compares the cancer group to reference data and explores associations with
      clinical factors. 383 alive and disease free patients and treated between 1992
      and 2005 were sent the survey of which 252 (66%) responded. Age (younger
      patients), T stage 3 and 4 and adjuvant radiotherapy were key factors in patients
      reporting problems with appearance. There was excellent correlation between the
      two questionnaires. A cut-off of less than 75 in the UWQOLv4 appearance item
      captured most of the problems raised in the DAS24. The cancer cohort had similar
      DAS24 scores to the general population sample and had more positive scores than
      the clinical reference group (burns etc patient). In conclusion the UWQOL
      appearance domain appears to be a suitable means of screening for appearance
      issues in this cohort and could act as a trigger for further assessment and
      treatment.

PMID- 18329950
TI  - Accuracy of intraoperative tissue staining in delineating deep surgical margins
      in oral carcinoma surgery.
AB  - The purpose of this study was to assess the accuracy of this tissue staining
      assessment of surgical specimens in delineating deep surgical margins in oral
      cancer surgery. Fifteen patients who underwent surgery for oral carcinoma were
      included in the study. Once the tumor was resected, a vertical section of the
      surgical specimen was taken from the central part of the tumor. The section was
      consecutively stained with 0.4% indigo carmine and 0.5% Congo red, and deep
      surgical margins were assessed using a digital microscope with a magnification
      power of 25-175x. The results of tissue staining analysis were compared with the
      corresponding results of conventional histopathological analysis with HE
      staining, which is considered the gold standard. The extent of carcinoma invasion
      could be visualized after the application of tissue staining solutions. Tissue
      staining analysis was accurate in 12 of the 15 patients (80%) in evaluating the
      closest deep surgical margin. There was no significant difference in the tumor
      margin distance between tissue staining and histopathological assessment in these
      12 patients (Wilcoxon signed-ranks test, P>0.63). The results of this study
      showed that intraoperative tissue staining of surgical specimens permitted visual
      inspection and assessment of tumor spread to surgical margin, although the method
      has some limitations. The method had a possible ability in controlling the deep
      surgical margin.

PMID- 18329951
TI  - Ecologically relevant genetic variation from a non-Arabidopsis perspective.
AB  - Ecologically relevant genetic variation occurs in genes harbouring alleles that
      are adaptive in some environments but not in others. Analysis of this type of
      genetic variation in model organisms has made substantial progress, and is now
      being expanded to other species in order to better cover the diversity of plant
      life. Recent advances in connecting ecological and molecular studies in non-model
      species have been made with regard to edaphic and climatic adaptation, plant
      reproduction, life-history parameters and biotic interactions. New research
      avenues that increase biological complexity and ecological relevance by
      integrating ecological experiments with population genetic and functional genomic
      approaches provide new insights into the genetic basis of ecologically relevant
      variation.

PMID- 18329952
TI  - Vibrational assignments for 7-methyl-4-bromomethylcoumarin, as aided by RHF and
      B3LYP/6-31G* calculations.
AB  - Infrared (4000-400 cm(-1)) and Raman (3500-50 cm(-1)) spectral measurements have
      been made for the solid sample of 7-methyl-4-bromomethylcoumarin. Electronic
      structure calculations at RHF/6-31G* and B3LYP/6-31G* levels of theory have been
      performed, giving equilibrium geometries, harmonic vibrational spectra and normal
      modes. Different orientations of bromomethyl group have yielded only two
      conformers, of which the most stable one lying lower from the other conformer by
      approximately 7.99 kJ/mol, is non-planar with no symmetry. A complete assignment
      of the vibrational modes, aided by the calculations, has been proposed. Coupled
      vibrations are manifest in many modes. Some spectral features, compared to 6
      methyl-4-bromomethylcoumarin, show changes across both IR and Raman spectra,
      involving mainly skeletal vibrations, and to a lesser degree, methyl and
      bromomethyl vibrations. Low-frequency vibrations below 150 cm(-1) are assigned to
      lattice modes.

PMID- 18329953
TI  - Potentiometric study of binary complexes of methyl 2-pyridyl ketone oxime, phenyl
      2-pyridyl ketone oxime and diacetyl monooxime with some transition and heavy
      metal ions in aqueous solution.
AB  - The complexation reaction between some oximes including methyl-2-pyridylketone
      oxime (MPKO), phenyl-2-pyridylketone oxime (PPKO) and diacetyl monooxime (DMO)
      with some transition and heavy metal ions Co2+, Ni2+, Zn2+, Pb2+, Fe2+, Fe3+,
      Cr3+ and La3+ has been studied potentiometrically in aqueous solution at 25+/-0.1
      degrees C and ionic strength (mu) of 0.1M supported by KCl. The overall stability
      constants logbeta's of respective species were obtained by computer refinement of
      pH-volume data using BEST program. The best model among the several proposed
      models was selected according to the lowest sigma(fit) value. The main species in
      binary systems are ML, ML2, MLH, MLH2, ML2H, ML2H2, MOHL, M(OH)2L, M(OH)L2 and
      M(OH)2L2 (L = MPKO or PPKO or DMO).

PMID- 18329954
TI  - Thinking activates EMG in scalp electrical recordings.
AB  - OBJECTIVE: Fast electrical rhythms in the gamma range (30-100Hz) in scalp (but
      not intracranial) recordings are predominantly due to electromyographic (EMG)
      activity. We hypothesized that increased EMG activity would be augmented by
      mental tasks in proportion to task difficulty and the requirement of these tasks
      for motor or visuo-motor output. METHODS: EEG was recorded in 98 subjects whilst
      performing cognitive tasks and analysed to generate power spectra. In four other
      subjects, neuromuscular blockade was achieved pharmacologically providing EMG
      free spectra of EEG at rest and during mental tasks. RESULTS: In comparison to
      the paralysed condition, power of scalp electrical recordings in the gamma range
      varied in distribution, being maximal adjacent to cranial or cervical
      musculature. There were non-significant changes in mean gamma range activity due
      to mental tasks in paralysed subjects. In normal subjects, increases in scalp
      electrical activity were observed during tasks, without relationship to task
      difficulty, but with tasks involving limb- or eye-movement having higher power.
      CONCLUSIONS: Electrical rhythms in the gamma frequency range recorded from the
      scalp are inducible by mental activity and are largely due to EMG un-related to
      cognitive effort. EMG varies with requirements for somatic or ocular movement
      more than task difficulty. SIGNIFICANCE: Severe restrictions exist on utilizing
      scalp recordings for high frequency EEG.

PMID- 18329955
TI  - Electrical stimulation of primary motor cortex within the central sulcus for
      intractable neuropathic pain.
AB  - OBJECTIVE: To assess the pain-relieving effects of motor cortex electrical
      stimulation (MCS) within the central sulcus and the predictive factors
      retrospectively. METHODS: Thirty-four patients with intractable neuropathic pain
      underwent MCS; 19 patients had cerebral lesions, and 15 had non-cerebral lesions.
      In selected 12 patients, test electrodes were implanted within the central sulcus
      and on the precentral gyrus. Twelve patients received both MCS and repetitive
      transcranial magnetic stimulation (rTMS) of the primary motor cortex. RESULTS:
      Pain reduction of > or =50% was observed in 12 of 32 (36%) patients with > or =12
      months follow-ups (2 patients were excluded because of short follow-up). In 10 of
      the 12 patients who received test electrodes within the central sulcus and on the
      precentral gyrus, the optimal stimulation was MCS within the central sulcus. In 4
      of these (40%) patients, positive effects were maintained at follow-ups. The pain
      reduction of rTMS significantly correlated with that of MCS during test
      stimulation. CONCLUSIONS: The test stimulation within the central sulcus was more
      effective than that of the precentral gyrus. In the selected patients, chronic
      stimulation within the central sulcus did not significantly improve long-term
      results. SIGNIFICANCE: The present findings suggest that an intra-central sulcus
      is one of the favorable targets for MCS.

PMID- 18329956
TI  - Proactive nurse management guidelines for managing intensive chemotherapy
      regimens in patients with advanced gastric cancer.
AB  - Patients with advanced gastric cancer have a poor prognosis. Intensive
      chemotherapy regimens may be effective for the treatment of this disease but may
      be associated with a significant number of severe adverse events. Optimal
      management of these adverse events can improve outcome for the patient.
      Currently, there is little information in the literature about the nursing
      management of this particular group of patients. This American study involved the
      nursing management of all patients with gastric or gastroesophageal cancer
      enrolled in clinical trials at a single center. Patients had close contact with
      research nurses and received education about adverse events and how to deal with
      them. Patients completed a detailed treatment diary for each cycle of treatment.
      Protocols were established for the management of emergent adverse events. The
      guidelines developed during this study could help to underpin the role of the
      specialist oncology nurse and improve the management of patients undergoing
      intensive chemotherapy for gastric and gastroesophageal cancer, with the
      potential of improving outcome, or at least quality of life, for the patients.
      The nurses' role should be pivotal in the management of intensive chemotherapy
      for gastric and gastroesophageal cancer.

PMID- 18329957
TI  - Multiple pathways regulated by the tumor suppressor PP2A in transformation.
AB  - Reversible protein phosphorylation plays a central role in regulating
      intracellular signaling. Dysregulation of the mechanisms that regulate
      phosphorylation plays a direct role in cancer initiation and maintenance.
      Although abundant evidence supports the role of kinase oncogenes in cancer
      development, recent work has illuminated the role of specific protein
      phosphatases in malignant transformation. Protein phosphatase 2A (PP2A) is the
      major serine-threonine phosphatase in mammalian cells. Inactivation of PP2A by
      viral oncoproteins, mutation of specific subunits or overexpression of endogenous
      inhibitors contributes to cell transformation by regulating specific
      phosphorylation events. Here, we review recent progress in our understanding of
      how PP2A regulates mitogenic signaling pathways in cancer pathogenesis and how
      PP2A activity is modulated in human cancers.

PMID- 18329958
TI  - "What do you do for a living?".

PMID- 18329959
TI  - Hypothermia for spinal cord injury.
AB  - BACKGROUND CONTEXT: Interest in systemic and local hypothermia extends back over
      many decades, and both have been investigated as potential neuroprotective
      interventions in a number of clinical settings, including traumatic brain injury,
      stroke, cardiac arrest, and both intracranial and thoracoabdominal aortic
      aneurysm surgery. The recent use of systemic hypothermia in an injured National
      Football League football player has focused a great deal of attention on the
      potential use of hypothermia in acute spinal cord injury. PURPOSE: To provide
      spinal clinicians with an overview of the biological rationale for using
      hypothermia, the past studies and current clinical applications of hypothermia,
      and the basic science studies and clinical reports of the use of hypothermia in
      acute traumatic spinal cord injury. STUDY DESIGN/SETTING: A review of the English
      literature on hypothermia was performed, starting with the original clinical
      description of the use of systemic hypothermia in 1940. Pertinent basic science
      and clinical articles were identified using PubMed and the bibliographies of the
      articles. METHODS: Each article was reviewed to provide a concise description of
      hypothermia's biological rationale, current clinical applications, complications,
      and experience as a neuroprotective intervention in spinal cord injury. RESULTS:
      Hypothermia has a multitude of physiologic effects. From a neuroprotective
      standpoint, hypothermia slows basic enzymatic activity, reduces the cell's energy
      requirements, and thus maintains Adenosine Triphosphate (ATP) concentrations. As
      such, systemic hypothermia has been shown to be neuroprotective in patients after
      cardiac arrest, although its benefit in other clinical settings such as traumatic
      brain injury, stroke, and intracranial aneurysm surgery has not been
      demonstrated. Animal studies of local and systemic hypothermia in traumatic
      spinal cord injury models have produced mixed results. Local hypothermia was
      actively studied in the 1970s in human acute traumatic spinal cord injury, but no
      case series of this intervention has been published since 1984. No peer-reviewed
      clinical literature could be found, which describes the application of systemic
      hypothermia in acute traumatic spinal cord injury. CONCLUSIONS: Animal studies of
      acute traumatic spinal cord injury have not revealed a consistent neuroprotective
      benefit to either systemic or local hypothermia. Human studies of local
      hypothermia after acute traumatic spinal cord injury have not been published for
      over two decades. No peer-reviewed studies describing the use of systemic
      hypothermia in this setting could be found. Although a cogent biological
      rationale may exist for the use of local or systemic hypothermia in acute
      traumatic spinal cord injury, there is little scientific literature currently
      available to substantiate the clinical use of either in human patients.

PMID- 18329960
TI  - Categorizing the world of registries.
AB  - The term registry is widely used to refer to any database storing clinical
      information collected as a byproduct of patient care. Despite the use of this
      single characterizing term (registry), these databases exist in various forms and
      support functions ranging from biomedical informatics and clinical research, to
      public health, epidemiology and evidence-based clinical practice. This ambiguous
      terminology impacts the ability to locate and learn about specific types of
      registries; the goal of this research project was to develop a more useful
      categorization scheme for registries. We thoroughly analyzed peer-reviewed
      publications related to registries. From our findings, we created a detailed
      definition for registries in healthcare (medical data registries, or MDRs) and
      outlined a set of characteristics common to all such MDRs. This framework, MDR
      OK, comprises five distinguishing features of registries, and is intended to
      provide a clear understanding of MDRs as a functional variety of databases, as
      well as to provide a framework for evaluation and categorization of registries
      and other data systems.

PMID- 18329961
TI  - Electromagnetic interference with pacemakers caused by portable media players.
AB  - BACKGROUND: Electromagnetic fields generated by electrical devices may cause
      interference with permanent pacemakers. Media players are becoming a common mode
      of portable entertainment. The most common media players used worldwide are
      iPods. These devices are often carried in a shirt chest pocket, which may place
      the devices close to an implanted pacemaker. OBJECTIVE: The purpose of this study
      was to determine if iPods cause interference with pacemakers. METHOD: In this
      prospective, single-blinded study, 100 patients who had cardiac pacemakers were
      tested with four types of iPods to assess for interference. Patients were
      monitored by a single-channel ECG monitor as well as the respective pacemaker
      programmer via the telemetry wand. iPods were tested by placing them 2 inches
      anterior to the pacemaker and wand for up to 10 seconds. To simulate actual use,
      standard-issue headphones were plugged into the iPods. To maintain consistency,
      the volume was turned up maximally, and the equalizer was turned off. A subset of
      25 patients underwent testing on 2 separate days to assess for reproducibility of
      interference. Pacemaker interference was categorized as type I or type II
      telemetry interference. Type I interference was associated with atrial and/or
      ventricular high rates on rate histograms. Type II interference did not affect
      pacemaker rate counters. Electromagnetic emissions from the four iPods also were
      evaluated in a Faraday cage to determine the mechanism of the observed
      interference. RESULTS: One hundred patients (63 men and 37 women; mean age 77.1
      +/- 7.6 years) with 11 single-chamber pacemakers and 89 dual-chamber pacemakers
      underwent 800 tests. The incidence of any type of interference was 51% of
      patients and 20% of tests. Type I interference was seen in 19% of patients and
      type II in 32% of patients. Reproducibility testing confirmed that interference
      occurred regardless of pacing configuration (unipolar or bipolar), pacing mode
      (AAI, VVI, or DDD), and from one day to the next. Electromagnetic emissions
      testing from the iPods demonstrated maximum emissions in the pacemaker carrier
      frequency range when the iPod was turned "on" with the headphones attached.
      CONCLUSION: iPods placed within 2 inches of implanted pacemakers monitored via
      the telemetry wand can cause interference with pacemakers.

PMID- 18329962
TI  - Nanotoxicology and nanomedicine: making hard decisions.
AB  - Current nanomaterial research is focused on the medical applications of
      nanotechnology, whereas side effects associated with nanotechnology use,
      especially the environmental impacts, are not taken into consideration during the
      engineering process. Nanomedical users and developers are faced with the
      challenge of balancing the medical and societal benefits and risks associated
      with nanotechnology. The adequacy of available tools, such as physiologically
      based pharmacokinetic modeling or predictive structure-activity relationships, in
      assessing the toxicity and risk associated with specific nanomaterials is
      unknown. Successful development of future nanomedical devices and pharmaceuticals
      thus requires a consolidated information base to select the optimal nanomaterial
      in a given situation--understanding the toxicology and potential side effects
      associated with candidate materials for medical applications, understanding
      product life cycle, and communicating effectively with personnel, stakeholders,
      and regulators. This can be achieved through an innovative combination of
      toxicology, risk assessment modeling, and tools developed in the field of
      multicriteria decision analysis (MCDA).

PMID- 18329963
TI  - Evaluation of the physico-chemical properties of chitosan as a potential carrier
      for rifampicin, using voltammetric and spectrophotometric techniques.
AB  - Rifampicin is an antibiotic which, on a carbon paste electrode, shows an
      oxidation response of 0.492 V (vs. Ag/AgCl) at pH 7.0, due to the electroactivity
      of the hydroquinone group. Interaction of rifampicin with chitosan is strongly
      dependent on pH, species concentrations and contact time between the latter.
      Compared to the carbon paste electrode, electrodes modified with chitosan showed
      greater sensitivity, with optimum voltammetric profile obtained at pH 8.0.
      Spectrophotometric measurements indicate that rifampicin is strongly absorbed by
      chitosan at pH less than the pKa of the pharmaceutical, such behaviour being
      favourable for the use of chitosan as a carrier for the controlled release of
      rifampicin in the intestinal tract.

PMID- 18329964
TI  - Functionally distinct nucleosome-free regions in yeast require Rad7 and Rad16 for
      nucleotide excision repair.
AB  - In yeast, Rad7 and Rad16 are two proteins required for nucleotide excision repair
      (NER) of non-transcribed chromatin. They have roles in damage recognition, in the
      postincision steps of NER, and in ultraviolet-light-dependent histone H3
      acetylation. Moreover, Rad16 is an ATP-ase of the SNF2 superfamily and therefore
      might facilitate chromatin repair by nucleosome remodelling. Here, we used yeast
      rad7 Delta rad16 Delta mutants and show that Rad7-Rad16 is also required for NER
      of UV-lesions in three functionally distinct nucleosome-free regions (NFRs), the
      promoter and 3'-end of the URA3 gene and the ARS1 origin of replication.
      Moreover, rapid repair of UV-lesions by photolyase confirmed that nucleosomes
      were absent and that neither UV-damage formation nor rad7 Delta rad16 Delta
      mutations altered chromatin accessibility in NFRs. The data are consistent with a
      role of Rad7-Rad16 in damage recognition and processing in absence of
      nucleosomes. An additional role in nucleosome remodelling is discussed.

PMID- 18329965
TI  - Mechanical sensitivity of carotid body glomus cells.
AB  - Cultured glomus cells from rat carotid bodies were prepared for optical studies
      of intracellular calcium using the Fura-2 dye. The baseline calcium had a mean of
      about 40 nM showing either a relatively steady level or large calcium spikes.
      Some cells did not show measurable levels of [Ca(2+)](i). Stirring the fluid
      bathing the cultures induced large increases in [Ca(2+)](i) which were abolished
      when the bathing medium had zero Ca(2+) and EGTA. It is concluded that glomus
      cells respond to mechanical stimulation when directly exposed to this stimulus
      and are not protected by supporting structures. It is unknown if the electrical
      properties of these cells are also affected by mechanical challenges.

PMID- 18329966
TI  - 'Oxygen uptake efficiency slope' in trained and untrained subjects exposed to
      hypoxia.
AB  - We assessed the ability of the oxygen uptake efficiency slope, whether calculated
      on 100 and 80% of maximal exercise test duration (OUES(100) and OUES(80)), to
      identify the change in cardiorespiratory capacities in response to hypoxia in
      subjects with a broad range of V(O2 peak). Four maximal exercise tests were
      performed in trained (T) and untrained subjects (UT) in normoxia and at 1000,
      2500 and 4500 m. The mean reductions in maximal exercise capacities at 4500 m
      were the same in T subjects for V(O2 peak) (-30%), OUES(80) (-26%) and OUES(100)
      (-26%) whereas in UT subjects only OUES(100) (-14%), but not OUES(80) (-20%), was
      lower compared with V(O2 peak) (-21%, p<0.05). OUES(100) and OUES(80) were
      correlated with V(O2 peak) and the ventilatory anaerobic threshold in both
      groups. Multiple regression analyses showed that V(O2 peak), OUES(100) and
      OUES(80) were significantly linked to O(2) arterial-venous difference. The
      OUES(80) could be considered as an interesting sub-maximal index of
      cardiorespiratory fitness in normal or hypoxemic subjects unable to reach V(O2
      peak).

PMID- 18329967
TI  - Simultaneous determination of two Amadori compounds in Korean red ginseng (Panax
      ginseng) extracts and rat plasma by high-performance anion-exchange
      chromatography with pulsed amperometric detection.
AB  - A new simple, rapid and sensitive high-performance anion-exchange chromatography
      method with pulsed amperometric detection (HPAEC-PAD) was developed and validated
      for the simultaneous determination of two Amadori compounds, arginyl-fructose and
      arginyl-fructosyl-glucose in Korean red ginseng (Panax ginseng) extracts, rat
      plasma. Separation of the two target analytes was efficiently undertaken on
      CarboPac PA1 anion-exchange column with isocratic elution (400 mM sodium
      hydroxide and deionized water (90:10, v/v)) at flow rate 0.7 mL/min within 15 min
      of single chromatographic run. Under optimized conditions, the detection limits
      (signal-to-noise ratio equal to 3) were 20 and 25 ng/mL for arginyl-fructose and
      arginyl-fructosyl-glucose, respectively. Calibration curves of peak area for the
      two analytes were linear over three orders of magnitude with a correlation
      coefficients greater than 0.999. The accuracy of the method was tested by
      recovery measurement of the spiked samples which yielded good results of 94.15
      102.62%. This method was successfully applied to the quantification of arginyl
      fructose and arginyl-fructosyl-glucose in herbal extracts and in the plasma
      samples from rat.

PMID- 18329968
TI  - High-D-dimer plasma levels predict poor outcome in esophageal variceal bleeding.
AB  - BACKGROUND AND AIM: Variceal bleeding carries a high-mortality rate in patients
      with liver cirrhosis. Since coagulation and fibrinolysis are abnormal in these
      patients we evaluated whether or not abnormalities of these haemostasis systems
      were independently related to mortality. METHODS: Global coagulation, coagulation
      activation and fibrinolysis measurements were performed in 43 cirrhotics bleeding
      from esophageal varices at baseline and during follow-up and in 43 non-bleeding
      cirrhotic patients at baseline only. RESULTS: Baseline measurements of
      coagulation activation and fibrinolysis were more impaired in bleeders. In
      bleeders, prothrombin time, tissue type plasminogen activator antigen and D-dimer
      plasma levels were persistently more abnormal in patients who died. High-D-dimer,
      infection, Child-Pugh C class and MELD score >or=17 were the significant
      predictors of death at univariate analysis. Two different multivariate analyses
      to assess the independent prognostic value of these variables, one including the
      Child-Pugh class, the other including MELD, were performed. Independent
      predictors of death were high-D-dimer and infection, but not Child-Pugh class, in
      the former; MELD and infection, but not D-dimer, in the latter. CONCLUSIONS:
      Beside infection, high-D-dimer is a stronger predictor of death as compared to
      Child-Pugh C class, but not to a MELD score >or=17.

PMID- 18329969
TI  - Clinicopathological analysis of colorectal cancer liver metastasis and
      intrahepatic cholangiocarcinoma: are they just apples and oranges?
AB  - BACKGROUNDS/AIMS: Intrahepatic cholangiocarcinoma and colorectal cancer liver
      metastasis are the most primary and secondary adenocarcinoma of the liver,
      respectively. A large-scale long-term comparative study of these two cohort
      patient is lacking. METHODS: A total of 166 colorectal cancer liver metastasis
      patients and 206 intrahepatic cholangiocarcinoma patients who had undergone
      curative liver resection were retrospectively analysed. Among 206 intrahepatic
      cholangiocarcinoma, there were 47 intraductal growth type-intrahepatic
      cholangiocarcinoma and 159 non-intraductal growth type-intrahepatic
      cholangiocarcinoma. The demographics, clinicopathological data,
      immunohistochemical study and survival were analysed. RESULTS: The intrahepatic
      cholangiocarcinoma patients were more female-predominated, associated with
      hepatolithiasis, symptomatic, jaundiced, and with larger tumour size compared
      with those of colorectal cancer liver metastasis. Prognostic factors of
      intrahepatic cholangiocarcinoma were pathologic staging, histologic pattern and
      section margin; whereas prognostic factors of colorectal cancer liver metastasis
      were rectal origin, differentiation, section margin and bilobar distribution. CK7
      and CK20 differentiated majority of intrahepatic cholangiocarcinoma from
      colorectal cancer liver metastasis, while CDX2 and MUC5AC helped to differentiate
      inconclusive cases. The 1-, 3-, 5- and 10-year survival rates of colorectal
      cancer liver metastasis were 77%, 31%, 20% and 14%, compared to 53%, 21%, 13% and
      7% of intrahepatic cholangiocarcinoma (p=.0001). Furthermore, the survival of
      colorectal cancer liver metastasis was comparable to staged II intrahepatic
      cholangiocarcinoma (p=.8866) and intraductal growth type-intrahepatic
      cholangiocarcinoma (p=.1915). CONCLUSIONS: Demographics, precipitating factor,
      clinical manifestations, and prognostic factors of colorectal cancer liver
      metastasis and intrahepatic cholangiocarcinoma differed remarkably. High
      incidence of CDX2 and MUC2 expression in colorectal cancer liver metastasis and
      intraductal growth type-intrahepatic cholangiocarcinoma might explain their
      similar cytoarchitecture and survival.

PMID- 18329970
TI  - Ready, set, hire.

PMID- 18329971
TI  - Soft tissue deposits from head and neck cancer: an under-recognised prognostic
      factor?

PMID- 18329972
TI  - Is phenol a safe local anaesthetic for grommet insertion?

PMID- 18329973
TI  - Subglottic haemangioma in children: experience with open surgical excision.

PMID- 18329975
TI  - Splenic cyst presenting as severe hydronephrosis in a pediatric patient: part 2.

PMID- 18329976
TI  - Words of wisdom. Re: Identification of patients with prostate cancer who benefit
      from immediate postoperative radiotherapy: EORTC 22911 .

PMID- 18329977
TI  - Words of wisdom. Re: Radial distance of extraprostatic extension measured by
      ocular micrometer is an independent predictor of prostate-specific antigen
      recurrence. A new proposal for the substaging of pT3a prostate cancer .

PMID- 18329978
TI  - Words of wisdom. Re: Prognostic risk stratification and clinical outcomes in
      patients undergoing surgical treatment for renal cell carcinoma with vascular
      tumor thrombus .

PMID- 18329979
TI  - Words of wisdom. Re: Video endoscopic lymphadenectomy: a new minimally invasive
      procedure for radical management of inguinal nodes in patients with penile
      squamous cell carcinoma .

PMID- 18329980
TI  - Comment on: Kendler KS, Myers J, Torgersen S, Neale MC, Reichborn-Kjennerud T.
      (2007) The heritability of cluster A personality disorders assessed by both
      personal interview and questionnaire. Psychol Med; 37:655-665.

PMID- 18329981
TI  - Molecular epidemiology of Schistosoma mansoni: a robust, high-throughput method
      to assess multiple microsatellite markers from individual miracidia.
AB  - Schistosomiasis is one of the major unconquered infectious diseases afflicting
      people of developing countries, particularly in Africa. A deeper understanding of
      the epidemiology of schistosomes is complicated by the intravascular location of
      adult worms which makes them routinely unavailable for study. Their progeny,
      miracidia, which are hatched from eggs that are passed in feces, are available
      and can provide valuable insights about human infections, but they are small in
      size, hindering robust molecular analyses. Here we present a new high-throughput
      technique to assess the genotypes at 21 previously published microsatellite loci
      for individual miracidia of S. mansoni. The 21 loci can be amplified in four
      multiplexed PCR reactions; however, enough template is produced for approximately
      six PCR reactions, which allows for additional PCR reactions for resampling or
      obtaining additional data. We validated this technique using a pedigree study
      employing laboratory crosses of S. mansoni from Kenya to obtain sets of parents
      and offspring. Of 23 loci examined, 21 loci were found to be reliable: false
      alleles were rare and missing alleles due to allelic dropout occurred at only two
      loci in approximately 5% of the offspring. The latter type of error can be
      further reduced by reamplification which is possible with our method. This
      technique is amenable to a 96-well format thus facilitating analysis of larger
      samples of miracidia, allowing more robust molecular epidemiological studies of
      S. mansoni to infer population size, population structure, gene flow, mating
      systems, speciation, and host race formation.

PMID- 18329982
TI  - Structural integrity of the beta beta alpha-Metal finger motif is required for
      DNA binding and stable protein-DNA complex formation in R.KpnI.
AB  - Restriction endonuclease (REase) R.KpnI from Klebsiella pneumoniae is a
      homodimeric enzyme, which recognizes palindromic sequence GGTAC|C and cleaves
      generating 4 base 3' end overhangs. R.KpnI belongs to the HNH superfamily of
      nucleases, which are characterized by the presence of the beta beta alpha-Me
      finger motif. Structurally, this motif consists of a twisted beta-hairpin
      followed by an alpha-helix, and serves as a scaffold for side chains of residues
      involved in co-ordination of a divalent metal ion that is required for catalysis.
      Homology modeling studies of R.KpnI suggested a crossover structure for the alpha
      helix, which could possibly form dimeric interface and/or structural scaffold for
      the active site. We have evaluated the role of the residues present in this alpha
      helix in intersubunit interactions and/or stabilization of the active site. We
      show here that mutations of residues in the alpha-helix lead to a loss of the
      enzyme activity, but not dimerization ability. Intrinsic fluorescence and
      circular dichroism studies revealed that the loss of function phenotype was due
      to the structural perturbation of the beta beta alpha-Me finger motif. The
      results of mutational analysis suggest that the alpha-helix of the beta beta
      alpha-Me finger of R.KpnI plays an important role for the stability of the
      protein-DNA complex.

PMID- 18329983
TI  - The proceedings of the First London Colloquium on Status Epilepticus--University
      College London, April 12-15, 2007. Introduction.

PMID- 18329984
TI  - Absence status epilepticus: the first documented case?

PMID- 18329985
TI  - On the relevance of prolonged convulsive status epilepticus in animals to the
      etiology and neurobiology of human temporal lobe epilepsy.

PMID- 18329986
TI  - Changes in GABAA receptors in status epilepticus.

PMID- 18329987
TI  - Impact of receptor changes on treatment of status epilepticus.

PMID- 18329988
TI  - Inflammation modifies status epilepticus-induced hippocampal injury during
      development.

PMID- 18329989
TI  - Influence of brain development on status epilepticus.

PMID- 18329990
TI  - Role of genetic influences in animal models of status.

PMID- 18329991
TI  - The role of mitochondria in status epilepticus.

PMID- 18329992
TI  - Gene and protein expression in experimental status epilepticus.

PMID- 18329993
TI  - Status epilepticus: the past and the future.

PMID- 18329994
TI  - What is nonconvulsive status epilepticus, and what are its subtypes?
AB  - Prolonged nonconvulsive seizures have been recognized at least since the 19th
      century, although their inclusion within the rubric of status epilepticus was
      only formalized by Gastaut and colleagues after the Xth Marseilles Colloquium,
      held in 1962 (Gastaut et al., 1967). This was the first ever large meeting
      devoted to the topic of status epilepticus, and the concept that there were
      status forms for every seizure type was formulated there. The classification of
      status epilepticus derived from the 1962 colloquium thus mirrored exactly the
      newly evolved International Classification of Seizure Type (Gastaut, 1970). The
      main disadvantage of a classification based on seizure type is that it does not
      take into account the broader range of phenomenology of epilepsy, which is
      especially significant in regard to nonconvulsive seizures. A seizure type
      classification does not do justice to the variety of forms and to their widely
      varying pathophysiological basis, prognosis, or clinical setting.

PMID- 18329995
TI  - EEG criteria for nonconvulsive status epilepticus.

PMID- 18329996
TI  - When is epileptic encephalopathy nonconvulsive status epilepticus?

PMID- 18329997
TI  - How urgent is the treatment of nonconvulsive status epilepticus?

PMID- 18329998
TI  - Clinical pharmacology of parenteral use of antiepileptic drugs.

PMID- 18329999
TI  - The use of valproate and new antiepileptic drugs in status epilepticus.

PMID- 18330000
TI  - Which anesthetic should be used in the treatment of refractory status
      epilepticus?
AB  - While the treatment of refractory status epilepticus (SE) relies on the use of
      anesthetic agents, mostly barbiturates, propofol, or midazolam, the study of the
      available literature discloses that the evidence level is low. Therapeutic coma
      induction appears straightforward for generalized convulsive or subtle SE, but
      this approach is debated for complex partial SE. Each anesthetic has its own
      advocates, and specific advantages and risks; furthermore, several different
      protocols have been reported regarding the duration and depth of sedation.
      However, it seems that the biological background of the patient (especially the
      etiology) remains the main prognostic determinant in SE. There is a clear need of
      controlled trials regarding this topic.

PMID- 18330001
TI  - Clinical trial design in status epilepticus: problems and solutions.

PMID- 18330002
TI  - Intensive care unit management of patients with status epilepticus.
AB  - The intensive care unit management of status epilepticus focuses on patients who
      are refractory to initial treatment, who have an underlying condition that
      require critical care management, or who experience respiratory or cardiovascular
      complications of their therapies. The available data suggest that failure of a
      first-line anticonvulsant agent to terminate status should lead to the use of a
      definitive therapy in general anesthetic doses. Midazolam, propofol, and
      phenobarbital have been used most frequently; the place of newer agents (e.g.,
      valproate, levetiracetam, or topiramate) remains to be determined.

PMID- 18330003
TI  - The surgical treatment of status epilepticus.

PMID- 18330004
TI  - Neuroprotection in epilepsy.
AB  - Neuroprotection following status epilepticus should encompass not only the
      prevention of neuronal death, but also preservation of neuronal and network
      function. This is critical because these aims are not necessarily equivalent;
      prevention of neuronal loss, for example, does not inevitably prevent
      epileptogenesis. There are endogenous neuroprotective mechanisms that can serve
      dichotomous roles (e.g. ERK 1/2 activation can result in either neuroprotection
      or promote neuronal death). The roles of potential endogenous mechanisms can
      depend upon the pattern and timing of their activation. The simplest exogenous
      neuroprotective mechanism is to halt seizure activity. Other approaches consist
      of early NMDA receptor antagonism or later inhibition of apoptotic pathways. The
      problem with the latter approach is that calcium accumulation results in the
      activation of a number of downstream pathways, the importance of which varies
      from region to region and in a cell-type specific manner. Neuroprotection in
      epilepsy is not a straightforward concept, and we need to be clear about our
      eventual objectives (e.g. preventing cognitive decline). There are numerous
      possible approaches to neuroprotection, and the efficacy of these depends upon
      their timing, the specific aims and even the method of status epilepticus
      induction.

PMID- 18330005
TI  - Is neurogenesis reparative after status epilepticus?

PMID- 18330006
TI  - Endogenous mechanisms of neuroprotection.

PMID- 18330007
TI  - Mechanisms of drug resistance in status epilepticus.
AB  - Refractory status epilepticus (RSE) is a major medical emergency, defined as
      severe form of SE that does not respond to first (benzodiazepines) and second
      (phenytoin, phenobarbital) treatment efforts with antiepileptic drugs (AEDs).
      Understanding the mechanisms of RSE is important to prevent or reverse its
      development. Based on both clinical experience and data from rat models of SE,
      seizures that last more than 30 min become very hard to control by AEDs.
      Experimental studies have shown that the prolonged seizures of SE lead to
      progressive alterations of GABAA receptors, including reduced surface expression
      of these receptors by receptor trafficking, which would explain the loss of
      efficacy of benzodiazepines. In addition to AED target alterations, SE-induced
      overexpression of drug efflux transporters, such as P-glycoprotein (Pgp), in the
      brain may be involved in the resistance to AEDs (including phenytoin and
      phenobarbital) that are Pgp substrates. However, recent experiments of our group
      did not indicate that Pgp plays any important role in drug resistance of SE.
      Improved understanding the molecular mechanisms underlying AED resistance in SE
      will ultimately provide new treatment options for RSE.

PMID- 18330008
TI  - What is animal experimentation telling us about new drug treatments of status
      epilepticus?
AB  - Basic research is mostly focused on the consequences of status epilepticus (SE)
      in terms of neuronal loss, behavior, epileptogenesis or disease-modifying effects
      such as preventing epilepsy or reducing seizure severity. Among the drugs tested,
      several were able to trigger neuroprotection but only a few had disease-modifying
      effects. At this point, many data are still missing, namely which drugs could
      efficiently stop SE or which mechanisms of action should be searched for to
      prevent the harmful consequences of SE.

PMID- 18330009
TI  - The epidemiology of convulsive and nonconvulsive status epilepticus.
AB  - Epidemiologic studies of status epilepticus (SE) depend on clear definitions of
      terms. Such a definition is available for convulsive generalized SE, but clear
      definitions of nonconvulsive SE (NCSE) are lacking. This as well as clinical
      difficulties to diagnose NCSE are one source of underascertainment. The minimal
      incidence of SE in the Caucasian population of industrialized countries is about
      20/100,000/year. It depends on age, ethnic background and possibly gender. Case
      fatality rates lie between 1.9 and 40% depending on age, etiology and duration of
      the SE. Effective treatment can improve and focal SE itself may impair case
      fatality. Clearly increased rates of long term case fatality in patients with
      symptomatic SE suggest that these patients should be considered a population at
      high risk.

PMID- 18330010
TI  - Cognitive outcome of status epilepticus in adults.
AB  - There is no doubt that structural morphological brain lesions and malformations
      in epilepsy represent major etiological factors for the cognitive impairments
      seen in this disease. The role of epileptic activity and seizures for cognition
      and cognitive development, however, is less easily determined. Epileptic
      dysfunction ranges from interictal and periictal activity over self-terminating
      seizures to non-convulsive and convulsive status epilepticus, which appear the
      most severe conditions along this continuum. The decisive question in this regard
      is as to whether cognitive impairments observed in the acute epileptic condition
      are reversible or not. Impairments from interictal or postictal epileptic
      dysfunction are reversible and may interfere at most with brain maturation and
      cognitive development in the young patient. Seizures and ictal dysfunction in
      contrast, even when reversible, can leave a permanent trace which extends the
      phase of postictal recovery. As for status epilepticus and subsequent cognitive
      decline it often remains open whether the epileptic condition itself or the
      underlying clinical condition is causative for the aftermath. While there is
      evidence for both possibilities, group data from neuropsychological cross
      sectional and longitudinal studies indicate that more severe mental impairments,
      which in turn indicate more severe clinical conditions, appear to be a risk
      factor for sustaining status epilepticus, rather than that status epilepticus
      causes the cognitive decline. Reviewing the literature the cognitive condition in
      patients with status epilepticus varies with the type of epilepsy, the etiology
      of epilepsy, severity of the status, and the age of the patient.

PMID- 18330011
TI  - Outcome of status epilepticus in children.

PMID- 18330012
TI  - The risk of epilepsy after status epilepticus in children and adults.

PMID- 18330013
TI  - Out-of-hospital treatment of status epilepticus and prolonged seizures.

PMID- 18330014
TI  - Status epilepticus treatment guidelines.

PMID- 18330015
TI  - Bilateral vocal cord palsy after a retrosternal block.

PMID- 18330016
TI  - Subdural hygroma after dural puncture.

PMID- 18330017
TI  - [Clinical features of tuberculous pleurisy in viral hepatitis and HIV infection
      at penitentiaries].
AB  - In 1999 to 2005, the penitentiaries of Saint Petersburg and the Leningrad Region
      saw a drastic (almost 30-fold) increase in the number of patients with
      tuberculous pleurisy concurrent with viral hepatitis and HIV infection. The
      convicts with concomitant stages IVa, IVb, and IVc HIV infection currently fall
      ill with tuberculous pleurisy more frequently. In patients with viral hepatitis
      concurrent with HIV infection, tuberculous pleurisy develops and runs more
      gravely in proportion to the number of mixed infections than in those without
      infectious comorbidity. The patients with tuberculous pleurisy concurrent with
      viral hepatitis and HIV infection show a preponderance of acute progressive
      pleurisy with the frequently observed tuberculosis generalization and high
      mortality rates.

PMID- 18330018
TI  - [Pregnancy in the context of general adaptation syndrome].
AB  - Based on their own findings and the data available in the literature on pregnancy
      including that complicated by gestosis, the authors consider these conditions in
      the context of Selye's general adaptation syndrome. They identify its basic links
      (the autonomic nervous and cardiovascular systems) the function of which is
      affected by all the physiological and pathophysiological processes involved in
      its development. There is a high likelihood of baseline impaired adaption
      processes in these links, which may lead to an inability to accommodate
      (dysadaptation) by the moment of delivery. The paper gives the current
      interpretation of functional disorders, called Zangemeister'a triad in 1913, from
      the present-day points of view of the evaluation of pregnancy as the systemic
      inflammatory response syndrome and, probably, adaptation disease. Based on the
      results of analyzing the data available in the literature, the authors indicate
      physiologically the basic trends in the modulation of impaired development
      processes of the general adaptation syndrome towards the completion of pregnancy
      and surgical delivery.

PMID- 18330019
TI  - [Current approaches to the analgesia of spontaneous child birth].
AB  - The authors have compared various modes of spontaneous labor. Prolonged epidural
      infusion of naropine in combination with fentanyl has been found to cause a less
      motor block and therefore it may be used in the late first-to-second period of
      labor. Adequate analgesia ensures a smooth course of the second labor period and
      promotes the reduction in its duration and the correction of central hemodynamic
      and hormonal homeostastic disorders. The administration of moradol provides
      adequate analgesia of the first labor period, prevention, and elimination of
      abnormal labor activity, without exerting a depressive effect on maternal and
      neonatal respiration, which makes it possible to consider this procedure as an
      alternative mode of labor pain relief if there are contraindications to epidural
      analgesia.

PMID- 18330020
TI  - [Calcium antagonists in the preoperative preparation of pregnant women with
      gestosis].
AB  - Differential preoperative preparation of pregnant women with gestosis, which is
      aimed at eliminating dysfunction of the universal secondary calcium messenger and
      preventing further disorders caused by calcium antagonists, is accompanied by
      positive changes in the basic links of development of the general adaptation
      syndrome--the autonomic nervous and cardiovascular systems. A physiologically
      required reduction in total peripheral vascular resistance (TPVE) is achieved in
      pregnant women with hyper- and eukinetic hemodynamics. In pregnant women with
      hypokinetic type, who receive hydroxyethyl starch-130/04 solution in the infusion
      therapy protocol, there is elimination of its pathological increase and there is
      a tendency for its physiological reduction. Obviating the discrepancy between
      cardiac index and TPVE causes a change of the hyper- and hypokinetic hemodynamic
      types to the eukinetic one, which is attended by development of physiological
      sympathicotonia and by almost complete normalization of water metabolic
      parameters in pregnant women with gestosis.

PMID- 18330021
TI  - [Contemporary problems of occupational otorhinolaryngologic diseases: topical
      problems, some solutions and prospects].
AB  - The author presents contemporary structure of occupational otorhinolaryngologic
      morbidity reflecting prospective directions of advances in occupational
      otorhinolaryngology.

PMID- 18330022
TI  - [Prevalence of anemia in Japan].
AB  - The frequency of anemia in Japan is statistically higher than that of foreign
      countries. Especially, Japanese females frequently fall ill with iron deficiency
      anemia(IDA) because of decreased intake of iron. Secondary anemia is of the
      second-highest frequency. While primary hematological disorders account for only
      a small fraction of whole anemic patients, aplastic anemia is relatively frequent
      in the world-wide statistics. The frequency of myelodysplastic syndromes is now
      increasing with aging of the population. It is important to sustain our effort in
      assembling the data as to the prevalence of anemia.

PMID- 18330023
TI  - [Critical role of phosphatidylserine in hemolysis due to red blood cell
      enzyme/membrane defects].
AB  - The life span of human red blood cells (RBCs) is approximately for 120 days, and
      finally destroyed in reticuloendothelial systems. In pathological conditions,
      RBCs fall into premature death, i.e. hemolysis. Recent studies have unveiled that
      abnormal RBCs affected by either membrane disorders or enzyme deficiency as well
      as senescent RBCs shared the common feature, i.e. exposure of phosphatidylserine
      (PS) in the outer leaflet of the RBC membrane. Increased intracellular oxidative
      stress or enhanced calcium permeability impairs maintenance of phospholipid
      asymmetry, resulting in PS externalization. PS and other eat-me signals may
      contribute to recognition of abnormal RBC by macrophage. In this review, recent
      understanding of mechanisms underlying hemolysis are discussed.

PMID- 18330024
TI  - [Fanconi anemia--genotoxic stress and senescence of hematopoietic stem cells].
AB  - Fanconi anemia (FA) is a genetically heterogeneous inherited disorder
      characterized by progressive bone marrow failure, development of hematopoietic
      and solid malignancies and genomic instability. 13 FA proteins, identified to
      date, closely cooperate with familial breast cancer susceptibility proteins such
      as BRCA2 and PALB2, thereby forming 'the FA/BRCA molecular network'. Here I
      summarize our recent understanding of the molecular network and its significance
      in the pathogenesis of FA. I emphasize that FA provides an excellent genetic
      model for studying senescence and malignant transformation of human hematopoietic
      stem cells.

PMID- 18330025
TI  - [Paroxysmal nocturnal hemoglobinuria (PNH)].
AB  - Paroxysmal nocturnal hemoglobinuria is an acquired hematopoietic stem cell
      disorder. The most common clinical manifestations of PNH include intravascular
      hemolysis, venous thrombosis, and bone marrow failure. Hematopoietic stems cells
      with mutant PIG-A are present in normal marrow, but they are not noticed because
      they have no advantage under normal circumstances. In the setting of immune
      mediated bone marrow injury, such as that seen in aplastic anemia, PIG-A mutant
      cells are selected because they have a survival advantage based on deficiency of
      one or more GPI-anchored proteins. Expansion of the PIG-A-mutant clones occurs
      when other events that enhance the growth properties of the cells work together
      with the effects of the PIG-A mutation to enhance further the growth properties
      of the mutant cells.

PMID- 18330026
TI  - [Iron deficiency anemia].
AB  - Iron deficiency anemia (IDA) is defined as a disease of the reduced erythrocyte
      production with low content of hemoglobin, because of the lack of iron which is
      the most important constituent of hemoglobin. The main cause of the deficiency is
      blood loss including the mensturation and hemorrhage. The frequency of IDA is as
      high as 9.1% among 10 to 19 years cohort of apparently healthy women in
      metropolitan area of Japan. The pathophysiology of the deficiency, clinical
      features, laboratory findings, diagnosis and treatment are discussed as well as
      the basic findings of iron absorption mechanism in which the newly found factors
      such as DMT-1 and hepcidin are involved.

PMID- 18330027
TI  - [Myelodysplastic syndrome].
AB  - Myelodysplastic syndrome is a hematopoietic stem cell disorder characterized by
      ineffective hematopoiesis and leukemic progression. Accumulation of various kinds
      of genetic alterations in oncogene and tumor suppressor gene develops and
      accelerates the disease. Recently, alpha-catenin gene has been identified as a
      candidate gene in the 5q- anomaly. Diagnostic criteria have been updated by
      Valent et al. WHO classification has become popular and WHO classification-based
      prognostic scoring system will be employed to evaluate prognosis. In our country,
      clinical studies on vitamin K2+D3 and cyclosporine A were conducted in low-risk
      patients, and their efficacy and safety have been reported. In US, molecular
      targeting therapy with lenalidomide or demethylase is approved by FDA.

PMID- 18330028
TI  - [Anemia in patients with cancer].
AB  - Anemia is common in patients with cancer. The incidence and severity of anemia
      depend on the type and extent of the malignancy. Anemia may be the result of the
      malignancy itself, cancer treatment, blood losses, hemolysis or inflammatory
      cytokines associated with chronic disease. Anemia can have a profound impact on
      physical and psychosocial function and quality of life. However, in Japan, only
      iron supplementation and blood transfusion were available for the treatment of
      anemia with cancer. On the other hand, in Europe and America, erythropoietic
      agents such as erythropoietin and novel erythropoiesis stimulating protein (NESP)
      have been clinically used for anemia in patients with cancer.

PMID- 18330029
TI  - [Anemia in the elderly].
AB  - In the elderly, non-specific symptoms tend to come to the fore in addition to the
      symptoms resulted directly from anemia. Moreover, mild anemia could give the
      excessive effects to the heart and the lungs because of less function of organs.
      There is no great difference in the epidemiology of anemia in the elderly and the
      youth. However, the anemia associated with chronic illness, especially due to
      malignancy, is frequent in the elderly. The research for the original disease and
      its treatment should take priority in the anemia of chronic disorder.

PMID- 18330030
TI  - [Hemophilia--present and past].
AB  - Through a research of existing literature, the clinical manifestion, diagnosis
      and treatment of hemophilia A and B are described. This article reviews the
      recent progress of coagulation factor VIII and IX products, and the efficiency of
      bypass therapy with rFVIIa, etc., to induce immune tolerance induction in
      congenital hemophilia with inhibitors and acquired hemophilia. In the future, an
      explanation of the mechanism and prophylaxy of inhibitors and the progress of
      genetic therapy are expected.

PMID- 18330031
TI  - [Randomized double blind study on traditional Chinese medicine. evidence remains
      questionable].

PMID- 18330032
TI  - Recent highlights in clinical AIDS research.

PMID- 18330033
TI  - Legionnaires disease in a patient with AIDS.

PMID- 18330034
TI  - Images in HIV/AIDS. Elephantiasis nostras verrucosa secondary to Kaposi sarcoma:
      a rare case.

PMID- 18330035
TI  - Academic detailing: questions and answers.

PMID- 18330036
TI  - UN agency denies inflating cases of HIV deliberately.

PMID- 18330037
TI  - "Best-kept secret" for HIV-free Africa.

PMID- 18330038
TI  - HIV-associated nemaline rod myopathy: role of intravenous immunoglobulin therapy
      in two persons with HIV/AIDS.
AB  - Nemaline rod myopathy is a rare disease associated with muscle weakness and the
      presence of rod-shaped structures in the muscle fibers. Various acquired
      conditions have been associated with slow progressing presentations during
      adulthood. Several cases have been diagnosed in adults with HIV infection. The
      use of intravenous immunoglobulin (IVIG) has not been previously described for
      the treatment of these patients. We report the cases of 2 patients with HIV
      related nemaline rod myopathy who successfully responded to IVIG therapy.

PMID- 18330039
TI  - Editorial comment: HIV-associated adult-onset nemaline myopathy.

PMID- 18330040
TI  - Pneumocystis jiroveci pneumonia.

PMID- 18330041
TI  - [Popular art and public instruction: the regulation of film and cinema in
      imperial Germany].

PMID- 18330042
TI  - Legacies of legal reform: Muftis, the state, and gendered law in the Arab lands
      in the late Ottoman Empire.

PMID- 18330043
TI  - Hungary in World War I: the end of historic Hungary.

PMID- 18330044
TI  - The use of hepatocytes in evaluating time-dependent inactivation of P450 in vivo.
AB  - BACKGROUND: Time-dependent inactivation (TDI) of P450 is an important mechanism
      of drug interactions. The quantitative in vitro - in vivo correlation of TDI
      using systems such as human liver microsomes requires a comprehensive
      understanding of in vitro kinetics, pharmacokinetics, inhibition mechanisms, and
      homeostasis of the enzyme being inactivated. OBJECTIVE: To evaluate the use of
      hepatocytes in predicting TDI. METHODS: The theoretical basis of in vitro - in
      vivo correlation of TDI and the progress in using microsomes and hepatocytes to
      predict TDI in vivo are reviewed. RESULTS/CONCLUSION: Factors that may impact
      prediction accuracy, such as nonspecific binding, metabolism of inactivator,
      active transport, and sequential inhibitory metabolites, can be assessed by
      performing 'in vitro-in vitro' correlation between microsomes and hepatocytes.
      Together with microsomal data and the aid of computer modeling and simulation,
      hepatocytes provide a powerful tool to optimize the integrated approaches aimed
      at quantitatively predicting TDI in vivo.

PMID- 18330045
TI  - [Systematic review 2007: Primary treatments of testicular germ cell tumors after
      radical orchydectomy].
AB  - BACKGROUND: The "Standards, Options and Recommendations" (SOR)program in
      oncology, has been initiated in 1993 by the Federation of French Cancer Centres
      and is realised in collaboration with public and private clinicians,professional
      federations, scientific societies and since 2005 with National cancer institute.
      Its aims are to develop clinical practice guidelines (CPG), health technologic
      assessment reports and systematic reviews. By preparing the latter, it provides
      support to the scientific societies for the update of their CPG. In this context,
      the SOR, in collaboration with the French Association of Urology (AFU), has
      developed a systematic review on the management of nonseminomatous (NSTGC) or
      seminomatous(STGC) testicular germ cell cancer treated with primary radiotherapy
      (RT), chemotherapy (CT) or surveillance (SV) after radical orchidectomy. Today,
      80 % of patients with testicular germ cell cancer, including metastatic stage,
      can be cured. Actual challenges are to limit morbidity and late sequels of
      treatments while maintaining their therapeutic efficacy. Following this goal,
      surveillance, considered as a therapeutic option, is being broadly developed
      particularly for localised tumours. OBJECTIVE: To synthesize outcomes of patients
      with NSTGC or STGC treated with primary RT, CT or SV after radical orchidectomy.
      SEARCH STRATEGY: A systematic literature search has been performed on Medline
      between 01/2004 and 08/2007 and completed by the consultation of evidence based
      medicine websites, experts citations and further relevant references identified
      from trials revealed by electronic searches. SELECTION CRITERIA: Randomised
      controlled trial (RCT), systematic reviews, and observational studies
      (prospective or retrospective cohorts) in patients with locally or advanced NSTGC
      or STGC treated with primary RT, CT or SV after radical orchidectomy have been
      included. DATA ANALYSIS: Studies have been assessed for eligibility and quality
      by three independent reviewers. Authors were contacted to provide details of
      outstanding clinical trials. No quantitative analysis was initially planned
      because of the heterogeneity of experimental designs researched BIBLIOGRAPHICAL
      RESULTS: Twenty-nine trials have been included : 1 meta-analysis, 1 pooled
      analysis of 2 RCT, 4 non-inferiority RCT, 6 comparative studies (1 prospective, 5
      retrospective) and 17 observational studies (7 prospective, 10 retrospective).
      Nineteen references were for NSTGC and 10 for STGC. CONCLUSIONS: The choice of
      risk-adapted treatment for patients with locally NSTGC of the testis seems to be
      appropriate: SV for low risk patients and CT for others. For advanced stage, the
      suppression of bleomycine remains questionable. For local STGC, the choice of SV
      or CT versus RT needs to be confirmed by RCT with prolonged follow-up according
      to promising results in term of toxicity obtained with carboplatine or lower
      irradiation dose (20 Gy instead of 30 Gy). Finally, for advanced STGC, the
      utility of carboplatine single agent treatment versus cisplatin-based combination
      chemotherapy has not been proved.

PMID- 18330046
TI  - Work rehabilitation in Mainland China: striving for better services and research.
      Introduction.

PMID- 18330047
TI  - Faculty attitudes and scholarly productivity resulting from a seminar course.
AB  - OBJECTIVES: To determine faculty attitudes toward a professional seminar course
      for PharmD students, document scholarly production derived from the course, and
      ascertain whether that scholarly production or other faculty characteristics
      affected attitudes toward the course. METHODS: Faculty members served as
      facilitators for pharmacy students enrolled in a professional seminar course. A
      34-item survey instrument intended to identify faculty attitudes toward the
      course and document scholarly productivity was developed. All 40 faculty
      facilitators involved in the course were asked to complete the survey instrument.
      RESULTS: Of the 30 (75%) faculty members who completed the survey instrument, 20
      had an overall positive attitude toward the course. Faculty members had generated
      approximately 90 peer-reviewed scholarly works over a 9-year period as a result
      of the course. Significant associations were found between faculty members'
      attitudes toward the course and academic rank, academic department, and scholarly
      production derived from the course. CONCLUSIONS: Faculty members who had advanced
      academic rank, an appointment in the pharmacy practice department, and scholarly
      productivity as a result of serving as a facilitator for a Professional Seminar
      Course were more likely to have positive attitudes toward the course.

PMID- 18330048
TI  - New pharmacy faculty enculturation to facilitate the integration of pharmacy
      disciplines and faculty retention.

PMID- 18330049
TI  - Share with women. Cord blood banking--what's it all about?

PMID- 18330050
TI  - ADA advertising standards.

PMID- 18330051
TI  - ["We must save our pants": World War I and the masculine feeling of an inverted
      relationship of domination].

PMID- 18330052
TI  - The song of 1916.

PMID- 18330053
TI  - [North and the business of drinking water in Tarapaca, 1875-1918].

PMID- 18330054
TI  - Missing.

PMID- 18330055
TI  - War weariness or national reunion? Alsace, 1914-1918.

PMID- 18330056
TI  - Collaboration in pursuit of the epidemiology of health service use.

PMID- 18330057
TI  - Using data to inform future direction and meet community needs: through a unique
      research partnership.

PMID- 18330058
TI  - Improving the ORS: does glutamine have a role?

PMID- 18330059
TI  - Population mobility and spread of HIV across the Indo-Nepal border.
AB  - The article reviews information on the epidemiology of HIV/AIDS and behavioural
      networking to examine the role of population mobility in spreading HIV across the
      Indo-Nepal border. Documents were collected through a systematic search of
      electronic databases and web-based information resources, and the review focuses
      on studies about types of the virus, prevalence of HIV, and sexual and injecting
      networking. HIV-1 (subtype C) and HIV-2 were identified in Nepal. The prevalence
      of HIV was higher among male labour migrants and female sex workers (FSWs) who
      returned from India, especially from Mumbai, than in similar non-migrant groups.
      In the early 2000s, about 6-10% of Mumbai returnee men, compared to up to 4% of
      India returnee men and up to 3% of non-migrant men in the far-west Nepal, were
      identified with HIV. Likewise, when the prevalence of HIV among sex workers in
      Kathmandu was found to be 17% in 1999-2000, up to 44% of India returnee and 73%
      of Mumbai returnee FSWs were identified with the virus. These data are, however,
      based on small samples with questionable representativeness of the target
      populations and need to be interpreted cautiously. They also generate a biased
      impression that HIV was coming into Nepal from India. Recently, the possibility
      of a two-way flow of HIV across the Indo-Nepal border through injecting and
      sexual networking have been indicated by serological and behavioural data from a
      south-eastern cluster of Nepal and a north-eastern district of India. Although
      similar behavioural networks exist along other segments of the border,
      serological data are unavailable to assess whether and how extensively this
      phenomenon has caused the spread of HIV. Collaborative research and interventions
      covering both sides of the border are desirable to fully understand and address
      the prospect of HIV epidemics associated with cross-border population mixing.

PMID- 18330060
TI  - Does an L-glutamine-containing, glucose-free, oral rehydration solution reduce
      stool output and time to rehydrate in children with acute diarrhoea? A double
      blind randomized clinical trial.
AB  - This study assessed whether an oral rehydration solution (ORS) in which glucose
      is replaced by L-glutamine (L-glutamine ORS) is more effective than the standard
      glucose-based rehydration solution recommended by the World Health Organization
      (WHO-ORS) in reducing the stool volume and time to rehydrate in acute diarrhoea.
      In a double-blind, randomized controlled trial in a Mexican hospital, 147
      dehydrated children, aged 1-60 month(s), were assigned either to the WHO-ORS (74
      children), or to the L-glutamine ORS (73 children) and followed until successful
      rehydration. There were no significant differences between the groups in stool
      output during the first four hours, time to successful rehydration, volume of ORS
      required for rehydration, urinary output, and vomiting. This was independent of
      rotavirus-associated infection. An L-glutamine-containing glucose-free ORS seems
      not to offer greater clinical benefit than the standard WHO-ORS in mildly-to
      moderately-dehydrated children with acute non-cholera diarrhoea.

PMID- 18330061
TI  - Dietary intake and anthropometric status differ for anaemic and non-anaemic rural
      South African infants aged 6-12 months.
AB  - The study was undertaken to determine anthropometric measurements,
      sociodemographic data, and dietary intake of 238 anaemic and 241 non-anaemic
      rural South African infants aged 6-12 months. Logistic regression with anaemia as
      a dependent variable showed an odds ratio (OR) of 1.89 (95% confidence interval
      [CI] 1.01-3.52) for low birth-weight, 2.04 (CI 1.29-3.22) for maternal age 20
      years or younger, 2.21 (CI 1.29-3.76) for consumption of tea, and 0.40 (CI 0.26
      0.63) for formula feeding. The anaemic infants, aged 6- < 9 months, had a lower
      average weight gain per month than the non-anaemic infants (727 g vs 772 g; p =
      0.040, analysis of variance). Logistic regression with underweight as a dependent
      variable showed an OR of 3.55 (CI 1.26-10.01) for anaemia, and with stunting as a
      dependent variable, the OR was 2.71 (CI 1.46-5.02). Low birth-weight, a young
      mother aged 20 years or younger, and consumption of tea were identified as risk
      factors for anaemia, while formula feeding was shown to have a protective effect.
      The anaemic infants were more likely to show growth faltering.

PMID- 18330062
TI  - Distribution and determinants of body mass index of non-smoking adults in Delhi,
      India.
AB  - Data on height and weight of 3,428 non-smoking healthy adult subjects, obtained
      during an earlier community-based study in Delhi, India, on chronic respiratory
      morbidity due to ambient air pollution was analyzed to study the distribution of
      body mass index (BMI) and its determinants among adults in Delhi. The sample was
      drawn by systematic sampling from rural and urban areas of Delhi. In urban areas,
      the sampling frame was restricted to areas around air quality-monitoring
      stations. However, the areas were spread across the city and reflected wide
      economic spectrum. Subjects were classified as underweight, normal, overweight,
      and obese as per the criteria of the World Health Organization for BMI. The mean
      BMI of the entire sample was 22.14 +/- 4.61. It was higher among females, urban
      residents, and the higher-income group. Overall, 49.7% of the 3,428 subjects had
      a normal nutritional status, 24.8% were underweight, 19.4% overweight, and 6.1%
      obese. The prevalence of underweight was higher in rural areas (38.5%) and among
      the lower-income group (39.9%), while overweight and obesity were more common in
      urban residents (22.7% and 7.5% respectively), among females (21.7% and 7.7%),
      and the higher-income group (31.8% and 11%) (p < 0.05). The adjusted odds for
      underweight were 2.02 for rural subjects and 4.00 for the lower-income group. For
      overweight or obesity, odds were 5.6 for the higher-income group, 3.62 for urban
      residents, and 2.5 for females. It was concluded that problems of both
      underweight and overweight and obesity exist among the adults of Delhi. While
      females, residents of urban areas, and economically-better-off were more likely
      to be overweight or obese, residents of rural areas and those from lower-income
      groups were more likely to be underweight.

PMID- 18330063
TI  - Causes of death among women aged 10-50 years in Bangladesh, 1996-1997.
AB  - Limited information is available at the national and district levels on causes of
      death among women of reproductive age in Bangladesh. During 1996-1997, health
      service functionaries in facilities providing obstetric and maternal and child
      heath services were interviewed on their knowledge of deaths of women aged 10-50
      years in the past 12 months. In addition, case reports were abstracted from
      medical records in facilities with in-patient services. The study covered 4,751
      health facilities in Bangladesh. Of 28,998 deaths reported, 13,502 (46.6%)
      occurred due to medical causes, 8,562 (29.5%) due to pregnancy-related causes,
      6,168 (21.3%) due to injuries, and 425 (1.5%) and 259 (0.9%) due to injuries and
      medical causes during pregnancy respectively. Cardiac problems (11.7%),
      infectious diseases (11.3%), and system disorders (9.1%) were the major medical
      causes of deaths. Pregnancy-associated causes included direct maternal deaths
      (20.1%), abortion (5.1%), and indirect maternal deaths (4.3%). The highest
      proportion of deaths among women aged 10-19 years was due to injuries (39.3%)
      with suicides accounting for 21.7%. The largest proportion of direct obstetric
      deaths occurred among women aged 20-29 years (30.5%). At least one quarter
      (24.3%) of women (n = 28,998) did not receive any treatment prior to death, and
      47.8% received treatment either from a registered physician or in a facility.
      More focus is needed on all causes of deaths among women of reproductive age in
      Bangladesh.

PMID- 18330064
TI  - Vibrio cholerae in the environment: a simple method for reliable identification
      of the species.
AB  - A simple screening and identification protocol was assessed for the efficient
      distinction of colonies of Vibrio cholerae species from others obtained on
      thiosulphate citrate bile salts sucrose agar after isolation from different
      environmental specimens. It was demonstrated here that the yellow colonies
      (sucrose-fermenting), which are able to grow on nutrient agar without added NaCl
      and which present a positive oxidase reaction, can be confidently considered as
      presumptive V. cholerae. Confirmation of the identification was carried out using
      the API 20E microtest and by species-specific ompW-based polymerase chain
      reaction: 809 of 925 isolates obtained by this screening procedure were
      identified as V. cholerae by API 20E and confirmed by PCR. The results showed
      that the direct use of the PCR-based method for the definite identification of
      the screened colonies gave better results than the API 20E method: of a selection
      of 100 isolates presumptively identified as V. cholerae according to the proposed
      screening procedure, all gave a positive result with PCR but only 94 were
      confirmed by API 20E. This protocol provides reliable identification of V.
      cholerae species and is adapted to the capabilities of routine clinical, food
      testing and environmental microbiology laboratories.

PMID- 18330065
TI  - Knowledge of and perceptions about sexually transmitted diseases and pregnancy: a
      qualitative study among adolescent students in Uganda.
AB  - This article reports the findings of a qualitative research study carried out in
      Kabarole district, western Uganda. Knowledge of and perceptions about HIV/AIDS
      and pregnancy and how both relate to one another were elucidated from eight focus
      group discussions with 38 female and 32 male secondary students from four
      different schools. Widespread misinformation and misconceptions about
      contraceptives still exist as previously found in this area. There was a serious
      gap in knowledge and understanding of 'dual protection' against sexually
      transmitted diseases, including HIV/AIDS, and against pregnancy. Fertility was
      very highly valued, and many girls stated that they would want a child even if
      they were HIV-positive. Responses of girls showed that they were quite assertive
      in making decisions to use contraceptives. The reasons for students not being
      able to understand the interconnectedness of sexually transmitted diseases and
      pregnancy may lie in the fragmented fashion in which relevant health education is
      delivered through two separate programmes.

PMID- 18330066
TI  - Prevalence and public-health significance of HIV infection and anaemia among
      pregnant women attending antenatal clinics in south-eastern Nigeria.
AB  - HIV infection and anaemia are major public-health problems in Africa and are
      important factors associated with an increased risk of adverse pregnancy
      outcomes. The objective of this study was to determine the prevalence of HIV
      infection and anaemia among pregnant women attending antenatal clinics in
      southeastern Nigeria. To achieve this, a cross-sectional survey was conducted
      during July 2005-June 2006 using standard techniques. Of 815 pregnant women
      studied, 31 (3.8%, 95% confidence interval [CI] 2.5-5.1) were HIV-positive.
      Maternal age and gestational age were not associated with HIV infection (p >
      0.05). The prevalence of anaemia (Hb < 11.0 g/dL) was 76.9%, and 15 (1.8%, 95% CI
      0.9-2.7) had severe anaemia (Hb <7.0 g/dL). A significantly higher prevalence of
      anaemia was observed among individuals in their second pregnancy trimester (p <
      0.05) and those infected with HIV (p < 0.05). Since HIV and anaemia are
      preventable, antenatal care services could serve as a pivotal entry point for
      simultaneous delivery of interventions for the prevention and control of HIV
      infection and anaemia in pregnant women.

PMID- 18330067
TI  - Nutritional status, breastfeeding, and evolution of Infants with acute viral
      bronchiolitis.
AB  - Acute viral bronchiolitis is a common respiratory infectious disease of infancy.
      A prospective study was carried out with 175 infants aged up to six months to
      evaluate their nutritional and breastfeeding status as possible risk factors for
      unfavourable evolution of previously-healthy infants from a care hospital.
      Immunofluorescence test for virus and anthropometric assessment were performed.
      Outcomes were length of oxygen-use, length of hospital stay, and type of hospital
      unit needed. Seventy-three percent of the infants were well-nourished, 6%
      undernourished, 8.6% at a nutritional risk, 10.9% overweight, and 1.7% obese.
      Eighty-one percent of the undernourished and nutritionally at-risk infants and
      72% of the well-nourished, overweight, and obese infants did not receive
      exclusive breastfeeding. The median length of hospital stay was four days and of
      oxygen-use was 60 hours. The nutritional status did not affect the clinical
      course of previously-healthy infants with acute viral brochiolitis. The duration
      of exclusive breastfeeding, but not type of breastfeeding, was inversely related
      to the length of oxygen-use and the length of hospital stay. Shorter exclusive
      breastfeeding was observed in infants who were assigned to a paediatric ward or
      to an intensive care unit. In conclusion, longer duration of breastfeeding was
      associated with better clinical outcomes.

PMID- 18330068
TI  - Factors predisposing out-of-school youths to HIV/AIDS-related risky sexual
      behaviour in northwest Ethiopia.
AB  - Ethiopia is a developing country with a demographic profile dominated by a young
      population. Due to biological, psychological, sociocultural and economic factors,
      young people, particularly those aged 15-24 years, are generally at a high risk
      of HIV/AIDS and other reproductive health problems. This paper presents results
      of a cross-sectional descriptive study conducted in Bahir Dar town, northwest
      Ethiopia, to assess factors that predispose out-of-school youths to HIV/AIDS
      related risk behaviours. Both quantitative and qualitative data-collection
      methods were employed to conduct the study. For quantitative data collection, a
      household interview survey was conducted among 628 out-of-school youths, aged 15
      24 years, within the 17 kebeles (villages) of the town. The number of respondents
      in each kebele was assigned proportional to the size of kebele, and the required
      numbers of respondents within each kebele were selected through a systematic
      random-sampling technique. Qualitative data were collected by conducting five
      focus-group discussions with 46 participants and in-depth interviews with 10
      participants. Institutional ethical clearance and informed verbal consent from
      the study participants were obtained before undertaking the study. Of the 628
      study subjects, 64.8% had experienced sexual intercourse at the time of the
      survey. The mean age at first sexual commencement was 17.7 (+2) years. Of those
      sexually active, 33% had sexual intercourse with non-regular partners (the
      proportions were 40.6% among males and 24.7% among females, suggesting that males
      tended to be about two times more likely to have sex with non-regular sexual
      partners than females (odds ratio = 1.78, with 95% confidence interval 1.16
      2.73). Furthermore, consistent condom-use among those who had sex in exchange for
      money was low (36%). Alcohol intake, chewing of khat (a green leaf), low
      educational background, and being male were significantly associated with having
      sex with either a commercial or a non-regular sexual partner. In view of the
      magnitude of high-risk sexual behaviours among out-of-school youths that may
      expose them to HIV/AIDS and other sexually transmitted infections, efforts need
      to be exerted to deal with the identified predisposing factors and to address the
      problems of idleness, lack of jobs, and hopelessness.

PMID- 18330069
TI  - Salmonellosis in Lagos, Nigeria: incidence of Plasmodium falciparum-associated co
      infection, patterns of antimicrobial resistance, and emergence of reduced
      susceptibility to fluoroquinolones.
AB  - The present study was undertaken to examine the status of antimicrobial
      resistance in Salmonella-associated diseases, by verifying possible emergence of
      reduced susceptibility to fluoroquinolones in Salmonella isolates and determining
      the incidence of Plasmodium falciparum-associated co-infection with Salmonella
      serotypes. Antimicrobial resistance in clinical isolates of Salmonellae was
      examined for a 12-month period. Four hundred and forty-one patients comprising
      two groups were recruited. Group A comprised 235 patients diagnosed by clinicians
      of having pyrexia, and group B included stool samples of 206 patients presenting
      with gastroenteritis. Samples were cultured and isolates identified, and drug
      susceptibility testing was performed using the standard methods. Of the 235
      samples screened in group A, 42 Salmonella isolates and 107 Plasmodium spp. were
      identified. Of the 42 Salmonella isolates, 19 (45.2%) were Salmonella Typhi, 9
      (21.4%) S. Enteritidis, and 7 (16.7%) each of S. Paratyphi and S. Arizonae.
      Plasmodium spp.-associated co-infection with Salmonellae was observed in 16
      patients mostly in complicated typhoidal cases and S. Enteritidis-associated
      bacteraemia. Fifty-three of the 206 stool samples from group B patients were
      confirmed positive for bacterial pathogens, made up of 35 Salmonella and 18
      Shigella isolates. Of the Salmonella isolates, 18 (51.4%) were S. Enteritidis, 11
      (31.4%) S. Arizonae, 4 (11.4%) S. Paratyphi, and 2 (5.7%) S. Typhi. There was no
      statistically significant difference (p < 0.01) in antimicrobial resistance
      patterns exhibited among typhoidal Salmonellae isolated in 2000 and 2005. A
      similar trend in resistance was recorded for non-typhoidal Salmonellae (p <
      0.05). For the first time in Lagos, Nigeria, Salmonella isolates (10-18%) with
      reduced susceptibility to both ciprofloxacin and ofloxacin at MIC50 and MIC90
      values of 0.015 and 0.03 microg/mL respectively were found. Despite this
      development, ciprofloxacin and ofloxacin remain the drug of choice for severe
      cases of salmonellosis, although caution should be exercised by clinicians in
      their prescriptions such that fluoroquinolone antibiotic therapy is used only in
      laboratory-proven cases of typhoid fever and Salmonella-associated bacteraemia to
      preserve its efficacy.

PMID- 18330070
TI  - Determinants of persistent underweight among children, aged 6-35 months, after
      huge economic development and improvements in health services in Oman.
AB  - Over the last decades, health indicators have witnessed major improvements in the
      Sultanate of Oman. This study was aimed at factors associated with underweight
      among children in four regions of Oman, as, in 1998, underweight was prevalent
      among 17.9% of children aged less than five years. A case-control study was
      conducted in 2002: 190 cases were 6-35-month old children with weight-for-age < 
      2 z-scores. Controls were individually matched by village of residence, sex, and
      age. The questionnaire included anthropometry of children, child-feeding
      practices, morbidity, anthropometry of mothers, parity, birth-spacing, and
      socioeconomic characteristics. Conditional logistic regression was used for
      analyses. Birth-weight of < 2,500 g was strongly associated with underweight and
      also were height of mother, low level of education of mother, bad quality of
      water in households, diarrhoea of children in the last two weeks, and regular use
      of infant formula. Factors, such as birth-weight, height of mother, supply of
      safe water in household, and care for mothers and children were the determinants
      of persistent underweight after huge economic development and improvements in
      health services. Further research is also needed to investigate further specific
      determinants of low birth-weight in the Omani context and try to disentangle
      emaciation and determinants of linear growth retardation.

PMID- 18330072
TI  - A low-cost method to identify tubewells for longitudinal research on arsenic in
      groundwater.
AB  - Exposure to high concentrations of arsenic in tubewell groundwater from the
      shallow aquifers of Bangladesh could result in up to 300,000 arsenic-related
      cancer cases over the next four decades. Understanding the magnitude and temporal
      dynamics of this exposure, via longitudinal studies, is imperative for planning
      effective mitigation and management strategies. Appropriate methods are needed to
      identify tubewells for longitudinal sampling. A plastic band marked with a unique
      identification number was developed, and various methods for attaching the band
      to the tubewell were tested, resulting in the choice of a galvanized-iron split
      rivet. Two follow-up surveys at two and 14 months post-banding assessed the
      durability and longevity under field conditions in the JiVitA Project area in
      rural, northwestern Bangladesh. After two months, approximately 96.0% of the
      original bands on 1,063 tubewells were functional, although the rivets were
      partially corroded. After 14 months, approximately 65% of a subsample of the
      bands were functional. With further improvements to the rivets, these bands offer
      an inexpensive, durable, enumeration technology for longitudinal studies on
      groundwater arsenic.

PMID- 18330071
TI  - Childhood mortality due to drowning in rural Matlab of Bangladesh: magnitude of
      the problem and proposed solutions.
AB  - Drowning is an important cause of mortality among children in rural Bangladesh.
      Children aged 1-4 year(s) are at a high risk of death from drowning. Although
      deaths of children due to drowning in Bangladesh are acknowledged as an important
      cause of death, little effort has been made to address the issue of preventing
      deaths from this cause. This study has attempted to describe the problem and
      suggests possible prevention strategies, which may contribute to reducing
      childhood mortality from drowning. Data presented in this study were collected
      from Matlab where ICDDR,B has been maintaining a demographic surveillance since
      1966. During the study period from 1985 to 2000, 989 deaths from drowning were
      reported, of which 796 (80.5%) were children in the age-group of 1-4 year(s), 48
      (4.8%) were in the age-group of less than one year, and 145 (14.7%) in the age
      group of 5-19 years. During 1985-2000, death rate per 1,000 children due to all
      causes among children of 1-4-year age-group decreased appreciably from 20.7% to
      5.2%, while drowning-related deaths did not. Forty-five percent (n = 359) of
      drowning-related deaths occurred in ponds, 16.8% (n = 134) in ditches, 8.1% (n =
      64) in canals, and 4.4% (n = 35) in rivers. The sites of more than 25% of
      drowning-associated deaths were not recorded. Analysis of seasonal variation
      revealed that most deaths due to drowning occurred during April-October, i.e.
      mostly during the monsoon months. It was also observed that the majority (67%) of
      mothers of victims had no formal education. Deaths due to drowning were mostly
      associated with children aged 1-4 year(s) and were 20% more common among boys
      than among girls (odds ratio = 1.2, 95% confidence interval 1.04-1.38, p <
      0.012). The paper recommends some interventions to reduce the number of deaths
      due to drowning in rural Bangladesh, which include: (a) increasing awareness
      among mothers and close family members about the risk of drowning, (b) door
      fencing, and (c) filling of unused ditches and water holes around households.

PMID- 18330073
TI  - Assessment of effects of pre- and post-training programme for healthcare
      professionals about breastfeeding.
AB  - This retrospective study assessed the effects of pre- and post-training programme
      for healthcare professionals about breastfeeding. The study included 3,114
      mothers who had children aged 1-72 month(s). Their knowledge and behaviours
      relating to breastfeeding were evaluated. The mothers were randomly divided into
      two groups: the 'before' group included 2,000 women who were not informed about
      breastfeeding, and the 'after' group comprised 1,114 women who had been informed
      about breastfeeding. 56.2% and 66.1% of the mothers started breastfeeding within
      30 minutes after delivery, respectively, in the before and the after group (chi2
      = 29.31, p < 0.001). 16.7% and 36.5% gave exclusive breastfeeding for six months
      (chi2 = 72.85, p < 0.001), and 28.5% and 23.7% stopped breastfeeding within the
      first five months (chi2 = 17.20, p = 0.002). Ninety-four percent delivered in a
      hospital or in a primary healthcare centre. Therefore, prenatal and postnatal
      breastfeeding education and support courses may improve a woman's chance of
      starting and continuing to breastfeed her baby. In terms of the number of
      antenatal check-ups, since the differences between the two groups were
      significant (chi2 = 390.67, p = 0.000), the importance of the training programme
      about breastfeeding was highlighted. Follow-up interventions after training are
      suggested.

PMID- 18330074
TI  - Clinical complications, monitoring and management of perioperative mild
      hypothermia: anesthesiological features.
AB  - BACKGROUND AND AIM OF THE WORK: Perioperative hypothermia is a frequent
      occurrence and can lead to several complications, which adversely affect the
      patient's outcome, expecially in high risk patient. Nonetheless, central
      temperature is not frequently monitored in the clinical routine. The aim of this
      work is to make the point on complications, monitoring techniques, prevention and
      treatment of mild perioperative hypothermia. METHODS: We reviewed literature on
      cardiovascular, haemorragic, infectious, and other clinical consequences of mild
      intraoperative hypothermia, epidemiology and techniques, of temperature
      monitoring and efficacy of different approaches for the prevention and treatment
      of mild hypothermia. RESULTS: Cardiovascular, haemorragic and infectious
      complications are significantly more frequent in hypothermic than in normothermic
      patients. Elderly and high risk patients are more prone to develop perioperative
      hypotherma, and are more liable to hypothermia-related complications. The ideal
      monitoring site has to be chosen considering both the patients characteristics
      and surgical procedure. Once identified, hypothermia has to be treated and the
      most effective systems are represented by active forced-air skin warming system.
      Active prewarming during the preoperative period has been also demonstrated to be
      efficient in reducing the development of intraoperative hypothermia.
      Humidification and warming of inspired gases, and warming of intravenous fluids
      are useful techniques when used in a multimodal approach with active skin warming
      to maintain perioperative normothermia. CONCLUSIONS: All the patient undergoing
      surgery for more than 30 minutes should receive an accurate temperature
      monitoring and a correct management for the maintenance of normothermia. Reducing
      the incidence and severity of perioperative hypothermia has the potential for
      drastically reducing complication-related costs.

PMID- 18330075
TI  - Prevalence of imported malaria in Parma during 2005-2006.
AB  - BACKGROUND AND AIM OF THE WORK: Malaria is a protozoan infection caused by
      parasites of the genus Plasmodium (P. falciparum, P. ovale, P. vivax, P.
      malariae) that is transmitted from one human to another by female Anopheles
      mosquitoes. It can be considered a reemerging imported disease in our area
      because of increasing of movements from endemic countries, and nowadays it is the
      most common imported infection in Italy. This study describes the occurrence of
      imported malaria in our area between January 2005 and May 2006. METHODS: During
      17 months we analysed 170 blood samples belonging to 139 patients (95 foreigners
      and 44 Italians) with the clinical suspect of malaria. Samples were used to
      prepare orange acridine and Giemsa stained thin blood films for microscopic
      observation and to perform an immunochromatographic assay for the detection of
      specific plasmodia antigens. Molecular assays (nested-PCR and Real-time PCR) were
      also performed in order to confirm the diagnosis. RESULTS: Thirty-six cases of
      malaria were diagnosed: 35 in foreigners coming from Africa and only one in an
      Italian who lived in Chad. Thirty-three patients were infected by P. falciparum,
      1 by P. ovale, 1 by P. vivax, and a mixed infection by P. falciparum, P. ovale
      and P. malariae was also found. CONCLUSIONS: Malaria is usually associated with
      travels within areas where the infection is endemic and our data demonstrated
      that imported malaria in our area has a prevalence of 25.89%.

PMID- 18330076
TI  - Burden of hospitalizations due to Rotavirus infection in Emilia Romagna, Italy.
AB  - The aim of this study was to collect data on hospitalizations due to
      gastrointestinal diseases, in particular Rotavirus gastroenteritis (RVGE), in the
      Region of Emilia Romagna, Italy. The national hospital discharge database was
      used to evaluate the epidemiology of RV infections in the 2000-2003 period,
      analyzing only the principal diagnosis. The available age groups were 0-14 years,
      15-64 years and, >64 years. Hospitalization related costs were estimated through
      Diagnosis Related Group (DRG) rates even though a specific DRG for RVGE does not
      exist. In the 0-14yr. old subjects, RV were responsible for an average of 310 GE
      related hospitalizations per year and globally represented 17% of admissions for
      enteritis and 84% of hospitalized viral GE. Fifty-six percent of the enteritis
      was of undefined origin. Considering the three possible DRG codes to which the
      disease can be referred (184, 298, 422) and the classification of hospitals in
      two categories, the cost of each admission for RVGE ranged between 1,293.83 Euro
      and 2,263.79 Euro. RV seems to play an important role as a cause of severe viral
      gastroenteritis, although RV infections are certainly underestimated for several
      reasons, one of them being the low sensitivity of hospital discharge forms. Today
      we have safe and effective vaccines that can be used in order to protect from
      moderate/severe forms of RV-related diarrhea. The extensive use of these vaccines
      could reduce hospitalizations and related costs in industrialized countries.

PMID- 18330077
TI  - Visual reaction times in strabismic amblyopia: a case-control study.
AB  - BACKGROUND: Visual reaction times (RT) have been used for the evaluation of the
      response to visual stimuli in amblyopic subjects in a case-control study.
      MATERIALS AND METHODS: A Study Group, consisting in nine subjects with amblyopia
      and anomalous retinal correspondence, and a Control Group of nine normal
      subjects, were examined. In order to measure RT a test was carried out using a
      personal computer, for generating the visual stimuli on a special 14" monitor and
      for recording the response. A program was specifically created to record the
      dimensions of the stimuli and times of presentation in milliseconds. An
      electrographic tracing controlled the visual fixation. Visual stimuli of
      different dimensions were presented to the amblyopic eye, the dominant and non
      dominant eye, and in binocular vision, and RT were recorded. RESULTS: In all
      cases RT represented a decreasing function of the stimulus dimension, with no
      statistical difference between the two groups (p=0.471). In both groups, RT
      values deriving from the greatest stimuli were rather inferior to those measured
      with smaller stimuli (p<0.001). In the Study Group the same stimulus produced
      longer reaction times in the amblyopic eye compared with those of the dominant
      eye (p<0.001), as well as those recorded during binocular vision (p<0.001).
      CONCLUSIONS: RT to visual stimuli could supply objective information on uncertain
      or hidden amblyopia. The extension of the experimental protocol to a larger
      population under school age could provide a clinical application for the early
      diagnosis of sensory alterations.

PMID- 18330078
TI  - Release phenomena and toxicity in polymer-based dental restorative materials.
AB  - In this work, the origin of the release phenomena occuring in resin-based dental
      restorative materials is demonstrated using confocal fluorescence microscopy and
      tapping mode atomic force microscopy techniques. The surface structure
      (microcavities, protruded filler particles, grain boundaries, and cracks)
      produced by water environment on the surface of composite resins and resin
      modified glass-ionomeric cements (RMGICs) are shown. The water absorption and the
      subsequent weight decrease, induced by leaching process, have been measured by
      gravimetric analysis. The different toxicity effects induced by the component
      release are described.

PMID- 18330079
TI  - Treatment of wrist and hand fractures with natural magnets: preliminary report.
AB  - The Authors, after having defined the phenomenon and the biological
      characteristics of natural magnets, evaluate their ability in accelerating the
      formation of bone callus in hand and wrist fractures compared to treatment with
      immobilization in a plaster cast. Forty patients (4 females and 37 males) between
      20 and 86 years of age were treated. A small natural magnet was inserted in each
      of the plaster casts (diameter: 2cm, height: 0.5cm) made of 4 blocks in Neodymium
      Iron-Boron, capable of generating 4 magnetic poles (2 positive and 2 negative) of
      diagonal alternate polarity that produced a symmetric, quadruple static magnetic
      field. The created magnetic flow was wavelike, concentrated in one direction, and
      developed a force up to 12,500 gauss. From this study it has emerged that
      inserting a quadruple magnet in a plaster cast in hand and wrist fractures
      results in the formation of bone callus in an average time that is 35% inferior
      to the "standard" time. Accelerating the healing of the fracture is important
      since it reduces immobilization time for the joints involved, avoiding subsequent
      weakness and stiffness and allowing the patient to begin rehabilitative
      physiotherapy sooner, which permits a faster functional recovery.

PMID- 18330080
TI  - Tamoxifen vs Tamoxifen plus 13-cis-retinoic acid vs Tamoxifen plus Interferon
      alpha-2a as first-line endocrine treatments in advanced breast cancer: updated
      results of a phase II, prospective, randomised multicentre trial.
AB  - AIMS AND BACKGROUND: To demonstrate the efficacy of 13-cis-retinoic acid (RA) or
      Interferon alpha-2a (IFN alpha-2a) with Tamoxifen (TAM) in the treatment of
      advanced breast cancer. METHODS: Ninety-nine postmenopausal patients with
      advanced breast cancer, and a positive or unknown estrogen (ER) or progesterone
      (PgR) receptor status, were randomised to receive TAM 20 mg/m2/day orally (arm
      A), or TAM plus RA 1 mg/kg/day orally (arm B), or TAM plus IFN alpha-2a 3 MU
      thrice a week intramuscular (arm C). The three treatment groups were well
      balanced in terms of the main prognostic factors. RESULTS: Response was evaluable
      in 32 of the patients in arm A, 32 in arm B, and 30 in arm C. Intention-to-treat
      analysis showed no significant difference of response rate in the three arms (44%
      vs 38% vs 42%). After an eight years median follow-up, there was no significant
      between-group difference in median overall survival: 47.4 vs 38.2 vs 45.1 months.
      Side effects were negligible in arm A, but cutaneous (39%) and mucosal (62%)
      toxicities were frequent in arm B, and flu-like syndrome and/or myalgia (46%) in
      arm C. CONCLUSIONS: The administration of RA or IFN alpha-2a does not add
      anything to the therapeutic effects of TAM.

PMID- 18330081
TI  - Liposomal doxorubicin: a phase II trial.
AB  - BACKGROUND AND AIM OF THE WORK: In patients with disseminated endometrial
      carcinoma, doxorubicin is used as a single agent or in combination therapy. We
      have carried out a phase II clinical trial of liposomal doxorubicin in first-line
      therapy of women with disseminated endometrial carcinoma. METHODS: Between
      September 2001 and May 2003, 22 patients with histologically confirmed
      disseminated endometrial carcinoma, were enrolled in this study. Eleven patients
      had been previously treated with radiation, none of them had been treated with
      chemotherapy. Liposomal doxorubicin (40 mg/m2) was intravenously administered at
      4 week intervals until toxicity or progression. RESULTS: The most common adverse
      events were fatigue, anemia, pain, and dermatologic toxicity (EPP). Eight
      patients (36%) achieved a tumor regression (Complete response, CR 3; Partial
      response, PR 5), ten (46%) maintained stable disease, and four (18%) experienced
      increasing disease. CONCLUSION: Liposomal doxorubicin has a lower cardiologic
      toxicity than doxorubicin with a similar response rate in patients with
      disseminated endometrial carcinoma.

PMID- 18330082
TI  - Second-trimester maternal serum alpha-fetoprotein elevation and its association
      with adverse maternal/fetal outcome: ten years experience.
AB  - BACKGROUND: Alpha-fetoprotein (AFP) is the major serum protein in the embryonic
      stage and in the early fetal stage. The aim of this study was to determine any
      possible association between an "unexplained" elevation of maternal serum alpha
      fetoprotein (MSAFP) levels in the second trimester of pregnancy and adverse
      maternal/fetal outcome. METHODS: A retrospective cohort study, was carried out in
      the University of Parma, by reviewing all triple tests that had been found
      positive for neural tube defect screening, showing an "unexplained" MSAFP
      elevation (> or =2.5 multiples of the median [MoM]), which could not be ascribed
      to any apparent reason. These results were compared with those of negative
      controls (MSAFP <2.5 MoM) in order to evaluate the course and outcome of
      pregnancy. Statistical analysis was performed by chi-square test, Fisher's exact
      test, Student's t-test, and odds ratio calculation. RESULTS: We reviewed 16,747
      tests: 143 tests with high MSAFP levels were found, including 105 data already
      available. Out of them 21 tests were excluded from the study because of the
      presence of fetal malformations, chromosomal diseases, or late miscarriage. Among
      the 84 remaining pregnancies, 43 were significantly associated with increased
      rates of pregnancy pathology compared with the control group of 199 patients,
      with 25 complicated pregnancies. In addition, high MSAFP levels were correlated
      with a less favorable neonatal outcome in terms of low birth weight, Apgar score,
      and transfer to a neonatal intensive care unit. CONCLUSIONS: Unexplained
      elevation of MSAFP levels in the second trimester of pregnancy is associated with
      an adverse maternal/fetal outcome, possibly suggesting the need for a more strict
      management of pregnancies.

PMID- 18330083
TI  - Cervical length as a predictor of preterm delivery: gestational age-related
      percentiles vs fixed cut-offs.
AB  - BACKGROUND: To determine whether preterm delivery is more effectively predicted
      by sonographic cervical length measurement using fixed cut-off or gestational age
      specific percentiles. METHODS: One hundred and eight patients hospitalized for
      suspected preterm labor (PTL) were studied prospectively between the 20th and the
      33rd week of gestation. RESULTS: Cervical length below 15 mm, 25 mm and the 2.5th
      centile showed substantially equivalent odds ratios for delivery within 7 days
      (7.5, 7.6, and 7.1, respectively), while for delivery before the 34th week the
      odds ratios varied between 3.6 with cervical length <2.5rh centile and 6.2 with
      cervical length <25 mm. Moreover, the negative predictive value for delivery
      within 7 days exceeded 90% when cervical length was above 25 mm, the 10th and the
      2.5th percentile, and 85% when above 15 mm. CONCLUSION: The comparison of fixed
      and gestational age-specific cut-offs demonstrates a better reliability of fixed
      cut-offs (15 or 25 mm) in predicting preterm delivery, both before 34 weeks and
      within 7 days of the ultrasound examination.

PMID- 18330084
TI  - Mangafodipir-DPDP enhanced MRI visualization of a pancreatic adenocarcinoma
      previously undetected by extracellular contrast enhanced CT and MRI.
AB  - We report a case of adenocarcinoma of the head of the pancreas, occult at
      extracellular contrast enhanced MDCT and magnetic resonance imaging (MRI), which
      was detected by MRI only with the use of a tissue-specific contrast agent
      (Mangafodipir trisodium Mn- DPDP). The histological examination after
      duodenopancreatectomy confirmed the diagnosis. Contrast-enhanced multi-detector
      computed tomography (MDCT) is currently considered to be the reference method for
      diagnosing and staging of pancreatic adenocarcinoma. Endoscopic Ultrasounds (EUS)
      with fine needle aspiration (FNA) is an accurate but invasive procedure. The
      technological evolution of magnetic resonance imaging and the development of
      organ-specific contrast media for liver and pancreas have led to a progressively
      more extensive use of this method for the investigation of suspected lesions.
      Moreover, this technique is particularly useful when MDCT gives unclear or
      debatable diagnostic responses.

PMID- 18330085
TI  - Ultrasound screening in second and third trimester of pregnancy: an update.
AB  - Ultrasound screening of structural fetal malformations is mainly based on the use
      of ultrasounds during the second trimester of pregnancy. The diagnostic
      sensibility of ultrasounds varies in the different multicentric studies reported
      in literature and is correlated to different factors: gestation period, type of
      malformation, number of ultrasounds performed, operator experience, etc. Third
      trimester ultrasounds may identify late-onset malformations and offer adequate
      information for postnatal assistance.

PMID- 18330086
TI  - Inhalatory therapy training: a priority challenge for the physician.
AB  - Patients with asthma and COPD commonly use inhaled drugs. The 3 types of
      currently available devices for inhaled therapy (Metered-dose inhaler, dry powder
      inhaler, and nebulizer) are clinically equivalent. However, since many different
      inhalers are available for inhaled therapy, the choice of the delivery device is
      important for optimizing the results of aerosol therapy. Traditional press-and
      breathe Metered Dose Inhalers (pMDIs) have recently improved their ecological
      appeal, can be used in every clinical and environmental situation, their dosing
      is convenient and highly reproducible, but their efficient delivery remains
      highly technique dependent. Poor inhalation technique can be minimised by the use
      of add-on valved holding chambers, which are seldom used in the clinical practice
      possibly because they are cumbersome. Breath Actuated devices (BAIs), such as Dry
      Powder Inhalers (DPIs), which are environmental-friendly, safe, effective,
      reliable, portable and self-contained, overcome problems of handbreath co
      ordination associated with pMDIs usage, but their use is also undermined by
      common errors of inhalation technique in real life. Nebulizers are cumbersome and
      time-comsuming for use and maintenance, but their use needs less cooperation than
      inhalers. Although nebulizer practice is not always evidence-based, some
      patients, mainly elderly prefer nebulizers for regular long-term usage. Despite
      the introduction of newer devices, clear advantages of a particular delivery
      system over other inhalers in terms of compliance, preference, and cost
      effectiveness are not currently available. The objective of an ideal and easy-to
      use inhaler is far from reality. Patient education is the critical factor in the
      use and misuse of delivery devices and effectiveness of aerosol therapy. The
      choice of the device has to be tailored according to the patient's needs,
      situation, and preference. Whatever the chosen inhaler, education from health
      caregivers has a key-role for improving inhaler technique and compliance.
      Differences among delivery devices represent another challenge to patient use and
      caregiver instruction.

PMID- 18330087
TI  - Endoscopic submucosal dissection is useful and safe for intramucosal gastric
      neoplasms in the elderly.
AB  - BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) has recently
      gained popularity for use against intramucosal gastric neoplasms in Japan, but
      few studies have examined whether ESD is feasible for elderly patients. This
      study aims are to evaluate the efficacy and safety of ESD according to age in
      consecutive elderly patients treated with ESD. PATIENTS AND METHODS: Subjects
      comprised 116 patients (90 men, 26 women) with 125 lesions treated using ESD from
      November 2002 to March 2006 at Nagoya City University Hospital and Iwata
      Municipal Hospital, Japan. Patients were categorized into: Group A, <65-years-old
      (n=34); Group B, > or =65-years-old but <75-years-old (n=41); and Group C, > or =
      75-years-old (n=41). En bloc resection rate and treatment time were examined
      according to age, tumour size and location, and frequency of complications was
      examined according to age. RESULTS: Rate of concomitant disease was significantly
      higher in Group C than in the other groups. En bloc resection rates and median
      treatment times were 91.4% and 80 min in Group A, 91.1% and 97 min in Group B and
      86.7% and 110 min in Group C, respectively. No significant differences were noted
      between groups, or for en bloc resection rate and treatment time according to
      tumour size and location, or between groups for frequency of complications.
      CONCLUSIONS: ESD for gastric neoplasms is effective and safe in elderly patients,
      and may be positively recommended to elderly patients with intramucosal gastric
      neoplasms.

PMID- 18330088
TI  - Is combined 18F-fluorodeoxyglucose-positron emission tomography/computed
      tomography superior to positron emission tomography or computed tomography alone
      for diagnosis, staging and restaging of pancreatic lesions?
AB  - BACKGROUND AND STUDY AIMS: To evaluate whether combined 18F-FDG PET/CT has an
      additive value over 18F-FDG-PET or CT alone for diagnosis, staging and restaging
      of pancreatic lesions. PATIENTS AND METHODS: Forty-six consecutive patients (23
      women, 23 men; median age 62.5 years) underwent FDG-PET/CT. Analysis of PET, CT
      and fused PET/CT images was performed by 2 readers. Patients were divided into 2
      groups: diagnosis and staging of primary tumours (n=34) and restaging: screening
      for recurrent or progressive pancreatic cancer (n=12). Accuracy analysis was
      performed lesion-by-lesion and patient-by-patient. Results were correlated with
      histopathology or clinical follow-up. RESULTS: Ninety-five foci were identified
      on PET, 140 lesions on CT and 119 on PET/CT. Thirty-four lesions were defined as
      'definitely pathologic' and localised in pancreas, liver, lung or bone by all 3
      techniques with equal certainty. In 11 patients malignancy was ruled out with the
      highest certainty by PET/CT. All 3 modalities made 2 false positive diagnoses of
      malignancy and missed metastases or vascular ingrowth in 7 patients. The accuracy
      rate of PET/CT (91.2%) for diagnosis of primary pancreatic lesions is higher
      compared to CT (88.2%) and PET alone (82.3%). Also for locoregional staging
      PET/CT has a higher accuracy rate (85.3%) compared to CT (83.8%) and PET (79.4%).
      When used for restaging, sensitivity (90.0%) and accuracy rate (91.6%) were
      highest for PET and PET/CT. CT had a lower sensitivity (80.0%). CONCLUSIONS:
      Topographical assignment of 'spots' with high FDG uptake is superior with PET/CT
      compared to PET alone. Fused PET/CT has a slightly higher sensitivity and
      accuracy rate for diagnosis and locoregional staging of primary pancreatic
      lesions compared to CT alone. PET and PET/CT perform equally well in screening
      for recurrent or progressive pancreatic cancer, with high accuracy. Due to its
      unlimited access, lower radiation exposure and cost, multidetector row CT remains
      the imaging technique of choice for diagnosis, staging and screening for
      recurrent pancreatic cancer.

PMID- 18330089
TI  - The significance of beta-catenin, E-cadherin, and P-cadherin expressions in
      neoplastic progression of colorectal mucosa: an immunohistochemical study.
AB  - BACKGROUND AND STUDY AIMS: The purpose of the current study was to investigate
      the role of beta-catenin, E-cadherin and P-cadherin in colorectal carcinogenesis
      using tissue array method. PATIENTS AND METHODS: Core tissue biopsies were taken
      from paraffin-embedded tissue blocks of 167 cases including 26 normal mucosae
      (NM), 99 colorectal polyps (10 hyperplastic polyps (HP), 8 traditional serrated
      (TSA), 17 tubular (TA), 37 tubulovillous (TVA), and 27 villous adenomas (VA)), 14
      adenomas with intramucosal carcinoma (ACA), and 28 colorectal cancers (CCA).
      Immunohistochemistry was performed using antibodies to beta-catenin, E-cadherin,
      and P-cadherin. Distribution of positivity was assessed using percentage
      expression while an arbitrary grading scale was used for staining intensity.
      RESULTS: beta-catenin expression was cytoplasmic, membranous, and nuclear. Both E
      cadherin and P-cadherin expressions were confined to cytoplasmic-membranous
      compartments. Membranous expression of beta-catenin significantly decreased in
      CCA (p < 0.01). Nuclear beta-catenin expression significantly increased in close
      correlation with neoplastic sequence reaching its highest expression in ACA and
      CCA (p < 0.001). Polyps with intraepithelial neoplasia (IEN) showed significantly
      higher nuclear beta-catenin expression in parallel with increasing grades of IEN
      (p < 0.001). E-cadherin and P-cadherin expression increased in polyps, whereas a
      significant decrease in their expression was observed in CCA (p < 0.001) while E
      cadherin expression significantly increased in CCA compared to NM (p < 0.001), no
      such difference was observed in P-cadherin expression. CONCLUSIONS: Nuclear beta
      catenin expression correlating with the grade of IEN in polyps and carcinomas
      supports its role in colorectal carcinogenesis. E-cadherin and P-cadherin
      expressions in adenomas suggest that these molecules might have role in adenoma
      formation though not necessarily be involved in neoplastic progression.

PMID- 18330090
TI  - Regulation of hepatic microcirculation in stepwise liver resection.
AB  - BACKGROUND: After liver resection a small-for-size syndrome may result from the
      reduction of liver volume and additional liver damage caused by hepatic
      hyperperfusion. Therefore the influence of the extent of liver resection on liver
      perfusion is investigated. MATERIAL AND METHODS: A stepwise liver resection
      (removal of 30%, 70%, 90%, 95% and 97% of the liver) was performed under
      inhalation anaesthesia with isoflurane in 6 male Lewis rats. Besides systemic
      arterial and venous blood pressure the portal pressure and flow was measured and
      the sinusoidal perfusion was visualized. Sinusoidal diameter, intersinusoidal
      diameter and functional capillary density were determined. RESULTS AND
      CONCLUSIONS: A decrease in the portal flow but an increase in the portal pressure
      was observed. Sinusoidal diameter showed a steady but low increase when up to 70%
      of the liver was removed but a high increase after 90% or more of the liver was
      resected. This indicates a decompensation of a regulatory mechanism of sinusoidal
      perfusion.

PMID- 18330091
TI  - The tissue effect of second generation argon plasma coagulation (VIO APC) in
      comparison to standard APC and Nd:YAG laser in vitro.
AB  - BACKGROUND: The aim of this study was to evaluate the effect of 2nd generation
      argon plasma coagulation (VIO APC) with respect to the tissue destruction
      capacity, and to compare it with standard APC and Nd:YAG laser. METHODS: 2nd
      generation APC (VIO APC2, Erbe, Germany), standard APC (APC 300/Erbotom ICC 200,
      Erbe) and Nd:YAG laser (KTP/YAG XP 800; Laserscope, San Jose, California) were
      applied in 35 porcine livers. Using APC, power settings (30-120 W), application
      time (2 and 5 sec) and gas flow (1 and 2 l/min) were varied. Using Nd:YAG laser,
      30-60 W were applied (flow 21/min). Diameter and depth of tissue coagulation were
      evaluated. RESULTS: Using VIO APC, maximum coagulation depth was 6 mm (maximum
      diameter 15 mm). In comparison to standard APC, the coagulation effect was
      significantly higher (p < 0.001). There was no significant difference in the mean
      depth achieved by VIO APC and Nd:YAG laser using 30- 60 W and an application time
      of 2 sec (p < 0.05). Using maximum energy available for the 2 systems, maximum
      depth achieved by VIO APC (6 mm) was higher than the one caused by Nd:YAG laser
      (4 mm). CONCLUSIONS: VIO APC was more effective than standard APC. Using medium
      power and a limited application time, it was as effective as Nd:YAG laser. The
      high effectiveness of VIO APC should be a topic of clinical education.

PMID- 18330092
TI  - One-sided limb lymphedema in a liver transplant recipient receiving sirolimus.
AB  - Sirolimus (SRL) is associated with many side effects including
      hypercholesterolemia, anaemia, impaired wound healing and abnormal liver function
      tests. Limb lymphedema has only been reported several times in renal transplant
      recipients. We present a case of lower limb lymphedema that occurred in a 59-year
      old liver transplant recipient after being on a SRL regimen for seven months.
      Extensive diagnostic investigations could not reveal signs of infection, venous
      obstruction or malignancy. After discontinuation of SRL, the lymphedema gradually
      resolved during the next three months. The pathologic mechanism behind this
      phenomenon is unknown, but antiangiogenetic and antiproliferative properties of
      SRL have been hold responsible. Further studies are necessary to explain this
      rare side effect.

PMID- 18330093
TI  - Hyperferritinaemia not always a sign of iron overload.
AB  - The level of serum ferritin normally parallels the concentration of storage iron
      within the body. In the absence of chronic diseases elevated serum ferritin
      levels will lead to the diagnosis congenital haemochromatosis. However, there are
      genetic disorders with high ferritin levels without any sign of iron overload. A
      case history of a patient suffering from cataract at young age and high ferritin
      levels is described. Because his mother and his three sons also had cataract at
      young age and high ferritin levels the diagnosis hereditary hyperferritinaemia
      cataract syndrome (HHCS) was made. The diagnosis was confirmed by detection of
      one of the mutations responsible for the syndrome.

PMID- 18330094
TI  - Young female with pancreaticobiliary maljunction presenting with acute
      pancreatitis: a case report and review of the literature.
AB  - We report a case of pancreaticobiliary maljunction which presented with acute
      pancreatitis. Pancreaticobiliary maljunction and its complications are mostly
      observed in the Asian population. There are only few western publications
      concerning this subject. We reviewed the literature for current knowledge and
      opinions concerning the pathophysiology and optimal treatment, with special
      emphasis on the oncologic aspect of this condition. Those patients without a
      choledochal cyst should at least receive a prophylactic cholecystectomy. Firstly,
      to prevent further pancreatitis due to biliopancreatic reflux more or less
      promoted by gallbladder contraction, and secondly, more important, to prevent the
      occurrence of gallbladder cancer. Patients with choledochal cyst should receive a
      prophylactic cholecystectomy, and an excision of the extrahepatic bile duct,
      followed by hepaticojejunostomy.

PMID- 18330095
TI  - Primary malignant melanoma of the gastrointestinal tract: a case report and
      review of the literature.
AB  - Although most gastrointestinal melanomas are metastatic of origin, primary
      malignant melanomas of the gastrointestinal tract do exist. Over the last ten
      years, we encountered six patients with primary malignant melanoma of the mucosal
      lining of the gastrointestinal tract. The literature is reviewed, the
      pathophysiological aspects of these tumours are described and the surgical
      treatment is discussed.

PMID- 18330096
TI  - Simultaneous occurrence of metastasizing carcinoid tumour of the gallbladder and
      chromophobe renal cell carcinoma in a young man.
AB  - Carcinoid tumour is an endocrine neoplasia described for the first time in 1888
      and rarely observed in the extrahepatic bile ducts. Gallbladder carcinoid tumour
      was first reported by Joel in 1929. An endoluminal gallbladder lesion, with a
      bizarre echogenicity, and a mass in the upper pole of the left kidney were found
      in a 27 year-old man. The patient underwent a cholecystectomy with partial
      hepatectomy and a polar renal resection. Histological examination revealed a
      typical gallbladder carcinoid tumour with regional lymph nodal metastasis and a
      renal cell carcinoma, with morphological and histochemical features of the
      chromophobe type. This is a distinctive, rare variant, often described in the
      literature in association with other neoplastic and non-neoplastic diseases. To
      our knowledge, this is the first report of gallbladder carcinoid tumour with an
      unexpected aggressive behaviour in a very young patient, with concurrent renal
      cell carcinoma, chromophobe variant.

PMID- 18330097
TI  - Transanal endoscopic microsurgery (TEM) vs. radical surgery (RS) in the treatment
      of rectal cancer: indications, limitations, prospectives. A review.
AB  - BACKGROUND AND STUDY AIMS: Principal goal in the management of any patient with
      rectal cancer is to provide an optimal chance for cure while maintaining their
      quality of life. Transanal endoscopic microsurgery (TEM) is a minimal invasive
      procedure that allows full thickness local excision or rectal tumors. The role or
      TEM in the treatment of rectal cancer remains controversial. The aim of this
      study was to review the evidence related to the role of TEM compared to radical
      surgery in the treatment of rectal cancer. PATIENTS AND METHODS: We reviewed 5
      studies (two controlled randomized and three non-randomized) comparing outcome
      after TEM vs. radical surgery (RS), either open or laparoscopic, in patients with
      rectal cancer. We evaluated the results in terms of safety of the procedure as
      well as its efficacy. RESULTS: Hospital stay, complication rate and overall
      morbidity and mortality were lower in the TEM groups in all studies. With the
      exception of one study, recurrence was slightly (but non-significantly) increased
      in the TEM groups. No difference for T2 tumors with TEM vs. laparoscopic
      resection was seen though. Overall survival was not statistically different.
      CONCLUSIONS: TEM is a safe, effective minimal invasive method for treatment of T1
      rectal carcinomas and possibly T2 carcinomas in selected patients after
      neoadjuvant chemoradiation. Its role in advanced tumor stages should be further
      defined.

PMID- 18330098
TI  - Statins in hepatobiliary diseases: effects, indications and risks.
AB  - BACKGROUND AND STUDY AIMS: Statins are among the most frequently used
      medications. Our aim was to study their indications or contraindications in
      hepatobiliary diseases. PATIENT AND METHODS: This study was stimulated by a
      patient with PBC, marked hypercholesterolemia and cardiac problems. RESULTS:
      Besides a lipid lowering effect, statins have other benefits, such as prevention
      of arterosclerosis, reduction of the risk of developing diabetes and inhibition
      of fibrogenesis. The effects depend on the type of statin, the genetic and
      acquired characteristics of the patient and the interaction with other
      medications. Side effects such as myopathy and liver toxicity are rather rare but
      should be monitored. The use of statins in liver disease is not clearly defined.
      Hyperlipidaemia is a risk factor for arteriosclerosis in NAFLD (Non Alcoholic
      Fatty Liver Disease), but fibrates might constitute the treatment of choice.
      Preliminary data suggest that biochemical and histological improvement in NAFLD
      might be obtained with atorvastatin or pravastatin. The use of statins in the
      medical therapy of gallstones remains unclear. Combination with ursodeoxycholic
      acid therapy might have a beneficial effect in cases of stones with mixed
      composition. Patients with Primary Biliary Cirrhosis or with chronic cholestasis
      in general have high HDL-cholesterol levels but a large amount of Lipoprotein X
      particles, which have a protective effect. As such, statin therapy is often not
      really indicated. CONCLUSION: When cardiovascular problems arise in patients with
      chronic cholestasis, an underlying factor should be looked for. The lipid
      abnormalities depend also on the stage of the PBC.

PMID- 18330099
TI  - Management and treatment of chronic hepatitis B virus: Belgian Association for
      the Study of the Liver (BASL) 2007 guidelines.

PMID- 18330100
TI  - [The 14/2007 Law on Biomedical Research: comments on ethical and scientific
      aspects].
AB  - The Spanish Law on biomedical investigation is analyzed from the scientific and
      ethical points of view. In the author's opinion, some terms used in the text in
      order to avoid ethical and legal conflicts are not right from the biological
      point of view.

PMID- 18330101
TI  - [Legal reserve and other questions related to the use of DNA in criminal research
      (part I)].
AB  - Lately, there has been an expansion phenomenon in the use of DNA techniques in
      criminal investigation. Several of our European neighbouring countries are
      undertaking reforms in this area. However, the proliferation in the use of DNA is
      hindering a series of guarantees that up until present were considered settled.
      The exceptions to the judicial due process is an evident example of this trend.
      Examples of this can be seen in the last interpretation that the Supreme Court
      has made of the Spanish regulation and the last reform in Germany, both of which
      we will take a look at.

PMID- 18330102
TI  - [Eugenics: progress or backward movement?].
AB  - Throughout this article there is a critical analysis of how genetics presents a
      dilemma for "human progress". So much so, that the legal world aims to create
      unequivocal norms and guarantees in relation with eugenics in order to avoid
      attempting against human dignity. The document makes the reader reflect on the
      ethical problems that eugenics can entail.

PMID- 18330103
TI  - Protection of genetic data in medical genetics: a legal analysis in the European
      context.
AB  - This article is based in three ideas, namely: 1. All the questions in the field
      of "privacy" and "confidentiality" derived from genetic tests only must be taken
      into account if we deal with "personal data". 2. When we are dealing with
      personal genetic data, two aspects must be especially guaranteed: a) the freedom
      and autonomy of the individual; and b) the duty of secrecy in order to protect
      the privacy of the person. 3. Some conflicts can appear between these two aspects
      and we have to deal with them. The author analyses the supranational European
      legislation referring to this topic, according to with, genetic privacy must be
      guarantee. He also notes how Genetic medicine can give rise to a variety of
      conflicts of interests, and points out how the different legal texts object of
      study deal with this issue.

PMID- 18330104
TI  - [The Cagliari (Italy) Court authorizes the preimplantation genetic diagnosis].
AB  - Today, preimplantation genetic diagnosis (PGD) has been greatly accepted within
      the framework of positive law of many European countries. Nevertheless, in other
      countries, such as Italy, it is forbidden by law. The ruling of the Civil Court
      of Cagliari which has authorized its use to a Sardinian couple, has opened, in
      this way, a small crack to be able to asses possible modifications to the Italian
      regulation on this matter. This article analyses the ruling of the Civil Court of
      Cagliari (Italy) from an ethical and legal perspective. The criteria which is
      used to analyse the legitimacy or illegitimacy of the practice of PGD is
      analysed. That is, on reasons which could justify or not the transfer of embryos
      in vitro to the woman. With this objective in mind, the Italian and Spanish
      normative models which regulates this controversial subject are looked at. As a
      conclusion, a critical evaluation of the arguments presented is made.

PMID- 18330105
TI  - [Organic Law 10/2007, of October 8, regulating the police database on identifiers
      obtained from DNA: historic background and genetic view].
AB  - Recently, Basic Law 10/2007 of 8 October has entered into effect, which regulates
      the police database on identifiers that are obtained from DNA. In the following
      lines, the author reveals the process of approval of this law as well as
      approaching certain of its aspects from a genetic perspective.

PMID- 18330106
TI  - A comparative analysis of selected European guidelines and recommendations for
      biobanks with special regard to the research / non-research distinction.
AB  - Classifying an activity as research has considerable normative consequences: On
      the one side research activities are especially protected ("freedom of
      research"), on the other side stricter ethical rules legal regulations may apply
      to such activities, e.g. compulsory review by ethics committees. It is therefore
      important to find criteria to delimit research from non-research activities. The
      aim of the present study is to analyse some European guidelines and
      recommendations for biobanks and to see whether these documents provide comments
      that help to elucidate the research/non-research distinction.

PMID- 18330107
TI  - CHIMBRIDS project: Chimeras and Hybrids in Comparative European and International
      Research--scientific, ethical, philosophical and legal aspects. Summary,
      conclusions and recommendations.

PMID- 18330108
TI  - [Organic Law 10/2007, of October 8, regulating the police database on identifiers
      obtained from DNA].

PMID- 18330109
TI  - Effects of insect-vector preference for healthy or infected plants on pathogen
      spread: insights from a model.
AB  - Insects vector many plant pathogens and often have higher or lower densities on
      infected plants than on healthy plants. Two hypotheses may explain this
      observation: insects may preferentially orient toward and select one plant type
      (referred to as orientation preference) or insects may reside on infected plants
      for longer or shorter periods than on healthy plants (referred to as feeding
      preference). The effects of feeding preference and orientation preference were
      compared alone and in combination using a spatially explicit model. With feeding
      preference for healthy or infected plants, the qualitative relationship between
      the percentage of plants infected and the rate of pathogen spread was not
      affected. However, feeding preference for healthy plants increased rates of
      pathogen spread, whereas feeding preference for infected plants decreased rates
      of pathogen spread. Unlike feeding preference, orientation preference for healthy
      and infected plants produced qualitatively different relationships between the
      percentage of plants infected and the rate of pathogen spread. With orientation
      preference for healthy plants, the pathogen spread slowly when few plants were
      infected, but quickly once most plants were infected. In contrast, with
      orientation preference for infected plants, the pathogen spread quickly when few
      plants were infected, but slowly once most plants were infected. In sensitivity
      analyses, we found that assumptions about the latent period (time between
      infection and when insects can recognize a plant as being infected) and
      persistence (length of time an insect remains inoculative) altered the
      aforementioned effects in some cases. The results illustrate that feeding and
      orientation preference affect pathogen spread differently, highlighting the
      importance of elucidating the mechanisms that control vector preference for
      healthy versus infected plants.

PMID- 18330110
TI  - Reproduction and feeding behavior of Myzus persicae on four cereals.
AB  - Green peach aphid, Myzus persicae (Sulzer), does not overwinter outdoors in
      Minnesota; it arrives each spring on low-level jet streams from the south. After
      arrival, anholocylic reproduction occurs on numerous herbaceous species,
      including many common weeds, before movement to potato, Solanum tuberosum L. In
      investigating aphid feeding behavior on barrier crops, we observed winter wheat,
      Triticum aestivum L., colonized by green peach aphid. The Northern Great Plains
      grows 94,000 ha of potatoes and 20.5 million ha of small grain cereals each year,
      the latter potentially providing an early emerging and widely distributed green
      peach aphid host to influence early season potato colonization. Life tables
      statistics indicated green peach aphid had its highest reproductive potential
      among cereals on winter wheat, with rye (Secale cereale L.) > barley (Hordeum
      vulgare L.) > oats (Avena sativa L.). Green peach aphid was found to colonize
      barley, rye, and winter wheat, but not oats. Mean generation time, net
      reproductive rate, doubling time, and finite rate of increase were significantly
      different between host plants. Electrical penetration graph technique indicated
      mean nonpenetration duration by green peach aphid was significantly different
      among plant species, and significantly longer on winter wheat than on the other
      cereals. Mean xylem phase duration was not significantly different among plant
      species but sieve element salivation was of longest duration on potato. Phloem
      sap ingestion (E2) was also significantly different among plant species with
      longest E2 duration on winter wheat. This study demonstrates that this aphid can
      effectively use key cereals at the vegetative stage.

PMID- 18330111
TI  - Variation in acquisition of Fiji disease virus by Perkinsiella saccharicida
      (Hemiptera: Delphacidae).
AB  - Fiji leaf gall, caused the Fiji disease virus (genus Fijivirus, family
      Reoviridae, FDV), is a serious disease of sugarcane, Saccharum officinarum L., in
      Australia and several other Asia-Pacific countries. In Australia FDV is
      transmitted only by the planthopper Perkinsiella saccharicida Kirkaldy
      (Hemiptera: Delphacidae), in a propagative manner. Successful transmission of FDV
      by single planthoppers confined to individual virus free plants is highly
      variable, even under controlled conditions. The research reported here addresses
      two possible sources of this variation: (1) gender, wing form, and life stage of
      the planthopper; and (2) genotype of the source plant. The acquisition of FDV by
      macropterous males, macropterous females, brachypterous females, and nymphs of P.
      saccharicida from infected plants was investigated using reverse transcription
      polymerase chain reaction to diagnose FDV infection in the vector. The proportion
      of individuals infected with FDV was not statistically related to life stage,
      gender, or adult wing form of the vector. The acquisition of FDV by P.
      saccharicida from four cultivars of sugarcane was compared to assess the
      influence of plant genotype on acquisition. Those planthopper populations reared
      on diseased 'NCo310' plants had twice as many infected planthoppers as those
      reared on 'Q110', 'WD1', and 'WD2'. Therefore, variation in FDV acquisition in
      this system is not the result of variation in the gender, wing form and life
      stage of the P. saccharicida vectors. The cultivar used as the source plant to
      rear vector populations does affect the proportion of infected planthoppers in a
      population.

PMID- 18330112
TI  - Rise and fall of cotton aphid (Hemiptera: Aphididae) populations in southeastern
      cotton production systems.
AB  - The impact of natural enemies on cotton aphid, Aphis gossypii Glover (Hemiptera:
      Aphididae), populations in cotton, Gossypium hirsutum L., production systems in
      the southeastern United States was evaluated over 3 yr in irrigated commercial
      cotton fields. Fungal epizootics caused by the entomopathogen Neozygites fresenii
      (Nowakowski) Batko reduced aphid numbers to subthreshold levels in 1999, 2000,
      and 2001 and occurred consistently in early to mid-July in all 3 yr. Scymnus spp.
      were the most abundant aphidophagous predators, although other coccinellid
      species and generalist predators such as spiders, fire ants, heteropterans, and
      neuropterans also were present. Studies using arthropod exclusion cages
      demonstrated little impact of predators or parasitoids on aphid populations
      before fungal epizootics. Arthropod natural enemies were most abundant after
      epizootics and may have suppressed aphid populations late in the season. Seed
      cotton yield, and lint quality were not affected by aphicide applications in any
      year of the study. Implications of these findings for aphid management in the
      southeastern United States are discussed.

PMID- 18330113
TI  - Benzylideneacetone, an immunosuppressant, enhances virulence of Bacillus
      thuringiensis against beet armyworm (Lepidoptera: Noctuidae).
AB  - Benzylideneacetone (BZA) is a metabolite of gram-negative entomopathogenic
      bacterium Xenorhabdus nematophila, and it acts as an enzyme inhibitor against
      phospholipase A2 (PLA2). PLA2 catalyzes a committed biosynthetic step of
      eicosanoids, which mediate insect immune reactions to infection by microbial
      pathogens. This study tested a hypothesis that a putative immunosuppressive
      activity of BZA may enhance virulence of Bacillus thuringiensis against the fifth
      instars of Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae). In in vitro
      conditions, BZA significantly inhibited hemocyte microaggregation induced by B.
      thuringiensis and impaired hemocyte-spreading behavior of S. exigua in a dose
      dependent manner. Oral administration of BZA gave similar immunosuppressive
      effect on the hemocytes of the fifth instars. Although BZA itself did not possess
      any insecticidal activity on oral administration, when BZA was treated in a
      mixture with a low dose of B. thuringiensis spp. aizawai to fifth instars, the
      bacterial virulence was significantly enhanced. BZA also enhanced virulence of B.
      thuringiensis spp. kurstaki, which alone was of limited effectiveness against S.
      exigua. This study suggests that an immunosuppression by BZA is positively linked
      to potentiation of B. thuringiensis.

PMID- 18330114
TI  - Insecticidal properties and microbial contaminants in a Spodoptera exigua
      multiple nucleopolyhedrovirus (Baculoviridae) formulation stored at different
      temperatures.
AB  - The Spodoptera exigua (Hubner) multiple nucleopolyhedrovirus (SeMNPV) is
      currently being tested as a biological insecticide for use in greenhouse crops in
      southern Spain. We performed a study in which semipurified SeMNPV occlusion
      bodies (OBs) were formulated in phosphate-buffered saline, pH 6.5, with 5%
      (vol:vol) glycerol and 0.15% (wt:vol) sorbic acid, and they were stored at -20,
      4, or 25 degrees C during 18 mo. Initial aerobic counts (+/-SE) averaged 1.4 (+/
      0.17) x 10(7) colony-forming units/ml after 17-h incubation at 37 degrees C.
      Aerobic counts of microorganisms that contaminated OB formulations stored at 250C
      decreased markedly over the period of the study, whereas only small decreases
      were observed in counts from OBs stored at 4 or -20 degrees C. The principal
      microbial contaminants of OB suspensions were Enterococcus spp.,
      Enterobacteriaceae, and yeasts. Potential human pathogens (Salmonella, Shigella,
      and Vibrio species) were not detected, and populations of Staphylococcus aureus
      and Bacillus cereus were extremely low. Compared with newly formulated OBs, the
      estimated LD50 values of OBs stored at 25 degrees C increased by >16,666-fold
      over the 18 mo of storage, whereas LD50 values were not greatly affected by
      storage at 4 or -20 degrees C. Significant changes over time in OB concentrations
      were only observed in the 25 degrees C treatment. Complete degradation of viral
      DNA was observed at 25 degrees C but not in refrigerated or frozen OBs. We
      conclude that OB formulation with bacteriostatic or antioxidant additives,
      together with storage and distribution in refrigerated conditions, will likely
      result in an SeMNPV biopesticide shelf life that exceeds 18 mo.

PMID- 18330115
TI  - Evaluation on potential of wild hosts as trap plants for managing gramineous
      stemborers in maize based-agroecosystem.
AB  - As part of habitat management system to control cereal stemborers, various wild
      hosts used as trap plants were studied during the dry season from November 2003
      to March 2004 at Melkassa, central Ethiopia. Five wild hosts of the family
      Poaceae [Pennisetum purpurum (Schumach), Sorghum vulgare variety sudanense
      (Pers.), Panicum coloratum L., Sorghum arundinaceum Stapf, and Hyperrhania rufa
      (Nees)] were evaluated as trap plants in maize, Zea mays L.,-based agroecosystem.
      The results of the study showed that maize plots surrounded by all tested wild
      hosts had significantly lower mean percentage of foliage damage and stemborer
      density than maize monocrop plots 15 m away from the treatment blocks.
      Interestingly, mean foliar damage and stemborer density between maize plots
      surrounded by wild hosts and maize monocrop plots within the treatment blocks was
      not significant. Percentage of tunneled stalks was significantly greater in maize
      monocrop plots 15 m away from the treatment blocks than in maize plots surrounded
      by all tested wild host plant species. Moreover, the highest mean percentage of
      parasitism (62%) of Chilo partellus (Swinhoe) by Cotesia flavipes (Cameron) was
      recorded in maize plots surrounded by P. purpureum. Therefore, the findings
      revealed that these wild hosts have considerable merit to be used as trap plants
      in the development of strategies for managing cereal stemborers in maize crops.

PMID- 18330116
TI  - Flight take-off performance of Colorado potato beetle in relation to potato
      phenology.
AB  - The flight take-off frequency of adult Colorado potato beetles, Leptinotarsa
      decemlineata (Say), from potato plants, Solanum tuberosum L. 'Red Pontiac' at the
      bloom stage of development was 2.2-2.5-fold that of Colorado potato beetle from
      plants at the vegetative stage. Tests were conducted in a flight chamber over a
      period of 3 h. Prefeeding Colorado potato beetles for 48 h on potato plants at
      the bloom or at the vegetative stage before placing them into the flight chamber
      resulted in the same significantly higher flight take-off frequency from potato
      plants at the bloom stage than from plants at the vegetative stage. These results
      demonstrate that the factor in potato plants in bloom that stimulates the flight
      take-off of the Colorado potato beetle is independent of the feeding history of
      the beetles and begins acting only when the beetles are in the presence of the
      plant. According to these results, the dispersal of adult Colorado potato beetles
      from potato fields in bloom to younger potato fields with plants at the
      vegetative stage, previously reported in the literature, is at least partly
      explained by the effect of plant phenology on the frequency of flight take-off.
      Results confirm the value of planting potato fields of similar phenology over as
      wide an area as possible to reduce Colorado potato beetle dispersal between
      fields. Results also imply that staggering the planting dates of conventional
      potato refuge areas near Colorado potato beetle transgenic or conventionally
      resistant potato fields is a sound management practice, because it promotes the
      movement of wild beetles over to the adjacent younger resistant crops.

PMID- 18330117
TI  - Factors affecting localized abundance and distribution of lesser mealworm in
      earth-floor broiler houses in subtropical Australia.
AB  - Factors that influence the localized abundance and distribution of lesser
      mealworm, Alphitobius diaperinus (Panzer), in litter of two compacted earth-floor
      broiler houses in subtropical Australia were studied using various experimental
      manipulations. Numbers of lesser mealworms substantially increased inside caged
      areas and under uncaged empty feed pans placed in open areas of the houses. These
      populations were found to be localized and independent of chicken-feed, manure,
      and high beetle populations that normally occur under existing feed pans.
      Substantial horizontal movement of larvae to under feed pans was recorded.
      Placing metal barriers around these pans significantly restricted this movement.
      In almost all treatments, lesser mealworms typically peaked in numbers during the
      middle of the flock time. This temporal pattern of abundance also was observed
      under pans within barriers, where relatively low insect numbers occurred, but it
      was not observed in uncaged open areas (where chickens had complete access). It
      is likely that larvae do not establish in open areas, but fluctuate in numbers as
      they either move to refuges away from chickens or suffer high rates of mortality.
      In these refuges, larvae peak in numbers and then leave the litter environment to
      pupate in the earth floor before the end of the flock time. This behavior might
      be exploited for management of lesser mealworm by targeting applications of
      control agents.

PMID- 18330118
TI  - Relationships of abscised cotton fruit to boll weevil (Coleoptera: Curculionidae)
      feeding, oviposition, and development.
AB  - Abscised cotton, Gossypium hirsutum L., fruit in field plots planted at different
      times were examined to assess adult boll weevil, Anthonomus grandis grandis
      Boheman (Coleoptera: Curculionidae), use of squares and bolls during 2002 and
      2003 in the Lower Rio Grande Valley of Texas. Although boll abscission is not
      necessarily related to infestation, generally more bolls abscised than squares
      and abundances of fallen bolls were not related to the planting date treatments.
      During 2003, fallen squares were most abundant in the late-planted treatment.
      Although large squares (5.5-8-mm-diameter) on the plant are preferred for boll
      weevil oviposition, diameter of abscised squares is not a reliable measurement
      because of shrinkage resulting from desiccation and larval feeding. Fallen
      feeding-punctured squares and bolls were most abundant in late plantings but
      differences between fallen feeding-punctured squares versus fallen feeding
      punctured bolls were found in only one treatment in 2003. During the same year,
      fallen oviposition-punctured squares were more numerous in the late-planted
      treatment than in the earlier treatments. Treatment effects were not found on
      numbers of oviposition-punctured bolls, but fallen oviposition-punctured squares
      were more common than bolls in the late-planted treatment compared with earlier
      treatments each year. Dead weevil eggs, larvae, and pupae inside fallen fruit
      were few and planting date treatment effects were not detected. Living third
      instars and pupae were more abundant in fallen squares of the late-planted
      treatment than in the earlier treatments and bolls of all three treatments. This
      study shows that fallen squares in late-planted cotton contribute more to adult
      boll weevil populations than bolls, or squares of earlier plantings.

PMID- 18330119
TI  - Pymetrozine causes a nontarget pest, the Colorado potato beetle (Coleoptera:
      Chrysomelidae), to leave potato plants.
AB  - Pymetrozine is a selective insecticide that targets aphids. Published assessments
      of the effects of pymetrozine on nontarget organisms focus mainly on predatory
      insects, and they rarely indicate toxicity. In a laboratory bioassay, survival of
      Colorado potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera:
      Chrysomelidae), larvae was not affected by pymetrozine exposure. We subsequently
      used pymetrozine to implement low-aphid-density treatments in a field experiment
      that involved separate manipulations of Colorado potato beetle density.
      Unexpectedly, the addition of Colorado potato beetle adults and eggs did not
      increase the densities of Colorado potato beetle larvae in plots that were
      sprayed with pymetrozine (applied with water and an adjuvant). In control plots
      sprayed with water and adjuvant (without pymetrozine), addition of Colorado
      potato beetles increased densities of their larvae. Data collected on a smaller
      scale suggest that a behavioral mechanism underlies the population-level pattern:
      Colorado potato beetle larvae become more active and are less likely to remain on
      a host plant after exposure to pymetrozine. Thus, potato, Solanum tuberosum L.,
      growers who use pymetrozine against aphids also might benefit in terms of
      Colorado potato beetle control.

PMID- 18330120
TI  - Influence of canopy aspect and height on codling moth (Lepidoptera: Tortricidae)
      larval infestation in apple, and relationship between infestation and fruit size.
AB  - Monitoring systems based on traps with female attractants are expected to enhance
      forecasting of insect population size and damage. The optimal placement of such
      traps should match the small-scale distribution of ovipositing females. In the
      codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), fruit infestation
      takes place in proximity to the oviposition site. We characterized the within
      tree distribution of codling moth infestations and the size of uninfested fruit
      based on a survey of 40,000 apples (Malus spp.) from trees belonging to 160
      different apple genotypes and growing in two different environments. Each tree
      was subdivided into 12 sectors, considering canopy aspect (north, east, south,
      and west) and canopy height (bottom, middle, and top). This study revealed that
      fruit infestation by the first but not by the second generation of larvae
      correlated significantly with canopy aspect. Similarly, fruit size differed
      significantly between the north- and the south-facing tree side for the period of
      infestation by the first but not by the second larval generation. Significantly
      lower fruit infestation was observed on the north- compared with the south- or
      east-facing tree side for the first generation. A significant influence of canopy
      height on larval infestation was observed in three of eight assessments, in which
      the middle height level showed the highest infestations. Significant differences
      in within-tree distribution of codling moth infestation suggest that oviposition
      preference is guided by nonrandom factors including microclimate, fruit
      phenology, and wind direction. These cultivar-independent findings should be
      considered in future monitoring systems that focus on female codling moth.

PMID- 18330121
TI  - Effects of nitrogen and potassium combinations on yields and infestations of
      maize by Busseola fusca (Lepidoptera: Noctuidae) in the humid forest of Cameroon.
AB  - Field trials were set up in the humid forest zone of Cameroon to investigate the
      effects of combinations of different rates of nitrogen (N) (0, 60, and 120 kg N
      ha(-1)) and potassium (K) (0, 80, and 160 kg K ha(-1)) applied to the soil on the
      incidence and damage of the noctuid stemborer Busseola fusca (Fuller), and on
      maize, Zea mays L., yield. Each N/K combination had an insecticide control to
      assess yield losses due to borers. In contrast to N, K had no effect on plant
      growth and borer incidence and damage. Across seasons and days after planting,
      total plant dry matter (DM) production increased with N level and it was 1.2-1.9
      and 1.7-2.2 times, respectively, higher at 60 and 120 kg N ha(-1) compared with 0
      kg N ha(-1). Total DM at harvest was strongly related to the N content of the
      plant at 63 d after planting. At the early growth stage, borer abundance and stem
      tunneling tended to increase with N level, but percentages of dead hearts did not
      vary with treatment. Maize grain yields increased linearly with N level, but
      grain yield losses decreased depending on season. Grain yield losses were 11-18.2
      times higher with 0 kg N ha(-1) compared with 120 kg N ha(-1). The findings so
      far indicated that, soil application of N improves the nutritional status of
      maize, which consequently enhanced its tolerance to stemborer attacks. Improving
      soil fertility can thus be a very effective means of complementing integrated
      stemborer control in the humid forest zone of Cameroon.

PMID- 18330122
TI  - Baited traps may be an alternative to conventional pesticides in integrated crop
      management of chicory (Compositae) in South Africa.
AB  - Chicory, Chicorium intybus L. (Compositae), is a major field crop in the Eastern
      Cape Province of South Africa. Several pests feed on the leaves of the plant,
      resulting in reduced yield. The most important of these are the noctuid moths
      Helicoverpa armigera (Hubner), Chrysodeixis acuta (Walker), and Trichoplusia
      orichalcea (F.). The use of attract-and-kill traps offers an alternative to broad
      based insecticides in the control of these species. Three fields were treated
      with normal insecticides and three fields with yellow-baited traps. Eight
      additional traps were placed in each field, with half of the traps containing the
      insecticide 2,2-dichlorovinyl dimethyl phosphate (dichlorvos) and half without
      dichlorvos; and half yellow and half green. Total moth numbers and nonphytophage
      diversity were measured from these eight traps. Although no differences in H.
      armigera or T. orichalcea catches were observed between insecticide- and trap
      treated fields, numbers of C. acuta and the total number of moths were
      significantly higher in insecticide-treated fields. Yellow traps containing
      dichlorvos contained more moths than yellow traps without dichlorvos, or green
      traps with dichlorvos, or green traps without dichlorvos; but they also contained
      more nonphytophagous insects. Yellow traps also enhanced the catches of thrips on
      card traps associated with them. These results offer an opportunity for the South
      African chicory industry to reduce pesticide applications and thus mitigate
      environmental impacts.

PMID- 18330123
TI  - Comparison of arboreal beetle catches in wet and dry collection cups with
      Lindgren multiple funnel traps.
AB  - We compared the effectiveness of a dry collection cup (with an insecticide
      killing strip) to a wet collection cup (containing antifreeze) for use with
      Lindgren multiple-funnel traps in catching several common species of bark and
      wood-boring beetles, and their associates in southern pine forests. All traps
      were baited with either the binary combination of ethanol and (-)-alpha-pinene or
      the quaternary combination of (+/-)-ipsenol, (+/-)-ipsdienol, ethanol, and (-)
      alpha-pinene. We found that cup treatment had little, if any, effect on catches
      of Ips avulsus (Eichhoff) and I. grandicollis (Eichhoff) (Coleoptera:
      Scolytidae), Alaus myops (F.) (Elateridae), Chalcophora Solier species
      (Buprestidae), Temnochila virescens (F.) (Trogositidae), and Lasconotus Erichson
      species (Colydiidae). In contrast, catches of the following species were
      significantly less (by 40-97%) in traps with dry cups than in traps with wet
      cups: Hylobius pales Herbst and Pachylobius picivorus LeConte (Curculionidae);
      Buprestis lineata F. (Buprestidae); Acanthocinus obsoletus (Olivier), Arhopalus
      rusticus nubilus (LeConte), Monochamus titillator (F.) and Xylotrechus sagittatus
      sagittatus (Cerambycidae); Hylastes porculus Erichson and Xyleborinus saxeseni
      (Ratzeburg) (Scolytidae); and Thanasimus dubius (F.) (Cleridae). The same was
      true in at least one experiment for the following species: Dendroctonus terebrans
      (Olivier), Hylastes salebrosus Eichhoff, Hylastes tenuis Eichhoff, and
      Xylosandrus crassiusculus (Motschulsky) (Scolytidae). We conclude that cup
      treatment can have a significant impact on catches of some arboreal beetles in
      baited multiple-funnel traps. Anyone using multiple-funnel traps to capture
      arboreal beetles should evaluate the potential impacts arising from their choice
      of collection cup treatment to their trapping objectives and expectations. The
      issue of cup treatment may be particular important at low population levels when
      maximum trap efficiency is required such as in the detection of exotic insects at
      ports-of-entry and within quarantine and containment zones.

PMID- 18330124
TI  - Effect of mango weevil (Coleoptera: Curculionidae) damage on mango seed viability
      in Tanzania.
AB  - Studies were conducted at the horticulture unit of Sokoine University of
      Agriculture, Morogoro, Tanzania, to assess the incidence and effect of mango
      weevil, Cryptorhynchus mangiferae (F.) (Coleoptera: Curculionidae), infestation
      on mango, Mangifera indica L., seed viability. Three polyembryo mango cultivars
      ('Sindano nyeusi', 'Sindano nyeupe', and 'Dodo') as well as three monoembryo
      mango cultivars ('Ex-horticulture', 'Tango', and 'Bongwa') were collected and
      examined for the presence of C. mangiferae. The effect of seed damage on
      viability was assessed for both naturally and artificially damaged seeds.
      However, for artificially damaged seeds, the viability was assessed by cutting
      away 0, 25, 50, or 75% of the cotyledon before planting. In this experiment, only
      monoembryo mango cultivars were used. All the examined cultivars were infested by
      C. mangiferae, although at varying levels. Polyembryo mango cultivars were
      relatively more infested than monoembryo cultivars. Bongwa and Tango were least
      infested, whereas Sindano nyeusi recorded the highest C. mangiferae incidence.
      Germination rates of damaged seeds of polyembryonic cultivars differed
      significantly from the uninfested control, except for Sindano nyeusi. There were
      no significant differences in germination percentage among the three monoembryo
      cultivars, and all the cultivars differed significantly from the uninfested
      control. The germination rates of seeds with 25% of their cotyledons removed did
      not differ significantly from the undamaged seeds, indicating that monoembryo
      cultivar seeds can withstand up to 25% damage and germinate successfully.

PMID- 18330125
TI  - Kaolin affects blueberry maggot behavior on fruit.
AB  - This study assessed the effects of Surround (kaolin) on several behavioral
      parameters of female blueberry maggot, Rhagoletis mendax Curran (Diptera:
      Tephritidae). First fruit visited, walking, cleaning, and oviposition behavior
      were quantified in two-choice and no-choice assays where females encountered
      Surround-treated and untreated fruit of highbush blueberries (Vaccinium spp.). In
      two-choice assays, females had a propensity (68%) to first visit untreated
      blueberries. In two-choice and no-choice tests, number of walking bouts and
      duration of walking bouts were significantly shorter on the Surround-treated than
      on untreated fruit. Few oviposition attempts on fruit were observed, irrespective
      of treatments and assays. Chromameter measurements showed significant
      modification of the blueberry skin color parameters lightness, hue, and
      saturation between untreated fruit compared with fruit dipped once or twice in a
      suspension of Surround. Oviposition trials with field-treated fruit showed that
      blueberries treated with Surround had fewer oviposition scars than the control,
      and this was more pronounced with weekly applications of Surround. Uneven coating
      of the fruit by Surround in field applications may have resulted in higher
      acceptance rates by flies than in blueberries individually dipped and used in
      laboratory trials.

PMID- 18330126
TI  - Evaluation of traps and lures for mass trapping of Mediterranean fruit fly in
      citrus groves.
AB  - Mass trapping has proven to be a powerful weapon in the control of Ceratitis
      capitata (Wiedemann), and its application in Mediterranean countries has
      currently increased notably as a control method. In this study, the efficacy of
      newly developed traps and dispensers of attractants were assessed with the aim of
      finding the best trap and set the lifetime of the dispensers, thus improving the
      total efficacy of mass trapping. Efficacy trials with six different types of
      traps and six different types of female dispensers were carried out. Moreover,
      the lifetime of three female dispensers, including a new attractant composition
      dispenser with n-methyl pyrrolidine, were studied. Results show significant
      differences among the trap types using female attractants, with an advantage of
      nearly 3 times more catches in best trap. Tested female dispensers showed no
      significant differences in efficacy between trimethylamine and putrescine
      attractants regard n-methyl pyrrolidine, however we observed differences in
      lifetime between dispensers. Thus, there are significant differences among
      different types of traps and dispensers in efficacy, and the appropriate
      selection of the trap and dispenser will improve the mass trapping results.

PMID- 18330127
TI  - Comparative efficiency of Nannotrigona perilampoides, Bombus impatiens
      (Hymenoptera: Apoidea), and mechanical vibration on fruit production of enclosed
      habanero pepper.
AB  - The native bee Nannotrigona perilampoides Cresson (Apidae: Meliponini) has been
      evaluated with promising results in greenhouse pollination of Solanaceae in
      Mexico. However, no comparison has been done with imported bumble bees (Apidae:
      Bombini), which are the most common bees used for greenhouse pollination. We
      compared the foraging activity and fruit production of habanero pepper. Capsicum
      chinense Jacquin, by using N. perilampoides and Bombus impatiens Cresson in
      pollination cages. Both bee species collected pollen on a similar number of
      flowers per unit time, but N. perilampoides visited significantly more flowers
      per trip, lasted longer on each flower, and spent more time per foraging trip.
      Ambient temperature and light intensity significantly affected the foraging
      activity of N. perilampoides. Light intensity was the only environmental variable
      that affected B. impatiens. Except for the fruit set, there were not significant
      differences in the quality of fruit produced by both bee species; however, N.
      perilampoides and B. impatiens performed better than mechanical vibration for all
      the variables measured. The abortion of fruit caused the low fruit set produced
      by B. impatiens, and we speculate it might be due to an excessive visitation
      rate. Pollination efficiency per visit (Spear's pollination efficiency index) was
      similar for both bee species in spite of the significantly lower amount of pollen
      removed by N. perilampoides. We suggested that the highest number of flowers
      visited per foraging trip coupled with adequate amounts of pollen transported,
      and transferred between flowers, could explain the performance of N.
      perilampoides as a good pollinator of habanero pepper. Our experiments confirm
      that N. perilampoides could be used as an alternative pollinator to Bombus in hot
      pepper under tropical climates.

PMID- 18330128
TI  - Toxicity of plant essential oils and their components against Lycoriella ingenua
      (Diptera: Sciaridae).
AB  - Plant essential oils from 20 plant species were tested for their insecticidal
      activity against larvae of Lycoriella ingenua (Dufour) (Diptera: Sciaridae) by
      using a fumigation bioassay. Good insecticidal activity (>90%) against larvae of
      L. ingenua was achieved with essential oils of caraway seed Carum carvi (L.)],
      lemongrass [Cymbopogon citratus (D.C.) Stapf.], mandarine (Citrus reticulate
      Blanco), nutmeg (Myristica fragrans Houtt), cade (Juniperus oxycedrus L.),
      spearmint (Mentha spicata L.), cumin (Cuminum cyminum L.), and thyme red [Thymus
      vulgaris (L.)] oils at 30 X 10-3 mg/1 air. Among them, caraway seed, spearmint,
      cumin, and thyme red essential oils were highly effective against L. ingenua at
      20 x 10(-3) mg/ml air. Analysis by gas chromatography-mass spectrometry led to
      identification of 4, 9, 8, and 17 compounds from caraway seed, spearmint, cumin,
      and thyme red oils, respectively. These compounds were tested individually for
      their insecticidal activities against larvae of L. ingenua, and compared with the
      toxicity of dichlorvos. Carvacrol, thymol, linalool, cuminaldehyde, p-cymen,
      terpinen-4-ol, and carvone was effective at 10 x 10(-3) mg/l. The insecticidal
      activity of dichlorvos was 60% at 10 x 10(-3) mg/ml. Effects of four selected
      plant essential oils on growth of oyster mushroom, Pleurotus ostreatus, also were
      investigated.

PMID- 18330129
TI  - Particle films for managing arthropod pests of apple.
AB  - A two-season study showed that a calendar-based spray program to manage arthropod
      pests with kaolin (60 g/liter) applied at the rate of 450 liters/ha was effective
      against European apple sawfly, Hoplocampa testudinea (Klug) (Hymenoptera:
      Tenthredinidae); white apple leafhopper, Typhlocyba pomaria McAtee (Homoptera:
      Cicadellidae); apple red bug, Lygidea mendax Reuter (Heteroptera: Miridae); pear
      plant bug, Lygocoris communis (Knight) (Heteroptera: Miridae); and the apple rust
      mite, Aculus schlechtendali (Nalepa) (Acari: Eriophyidae). Although it reduced
      Curculionidae damage, the level of damage was still too high. It had no effect on
      apple maggot, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae); codling moth,
      Cydia pomonella (L.) (Lepidoptera: Tortricidae); and tarnished plant bug, Lygus
      lineolaris (Palisot de Beauvois) (Heteroptera: Miridae). Laboratory studies
      showed fewer gravid twospotted spider mites, Tetranychus urticae Koch (Acari:
      Tetranychidae), and fewer eggs laid by these females. The study also showed no
      effect of kaolin on Neoseiulus fallacis (Garman) (Acari: Phytoseiidae).

PMID- 18330130
TI  - Comparison of several traps for catching German cockroaches (Dictyoptera:
      Blattellidae) under laboratory conditions.
AB  - German cockroach, Blattella germanica (L.) (Dictyoptera: Blattellidae), catch by
      five types of traps and modifications of each, were tested under controlled
      laboratory conditions. Cockroach catch differed significantly among traps. Lo
      line trap caught the greatest number of cockroaches in the test arena for each
      size class (23% small nymphs, 39% of gravid females, and 60% of other size
      classes in the experimental arena). Jar traps caught the least number of
      cockroaches in the test arena for each size class (range, 7-23% of each size
      class trapped). Modifications of traps also altered catch of cockroaches. Food
      bait tablets increased catch significantly; however, increases were small (<10%).
      Size of traps did not affect catch; whole traps or half traps caught the same
      number of cockroaches. Jar traps were much less effective than sticky traps,
      catching only half the number of cockroaches as sticky traps. A thin layer of
      petrolatum was a more effective barrier in jar traps to cockroach escape than
      powdered Olancha clay. Traps with petrolatum caught about twice as many
      cockroaches as traps with clay. Trapping of any of six life stages was not
      significantly affected by catch of any of the other stages. Rather, trap catch of
      each life stage was dependent on the number of that life stage available in the
      experimental arenas. In conclusion, of the traps tested, the Lo-line trap was the
      most sensitive for measuring cockroach catch, whereas the Detector trap (one
      third of trap) was the most economical trap (greatest sensitivity for lowest
      cost).

PMID- 18330131
TI  - Differences in Phyllotreta cruciferae and Phyllotreta striolata (Coleoptera:
      Chrysomelidae) responses to neonicotinoid seed treatments.
AB  - Insecticidal seed treatments are used commonly throughout the Northern Great
      Plains of North America to systemically protect seedlings of canola (Brassica
      napus L. and Brassica rapa L.) from attack by the flea beetles Phyllotreta
      cruciferae (Goeze) and Phyllotreta striolata (F.) (Coleoptera: Chrysomelidae).
      Here, we investigated differential responses by the two flea beetle species to
      the neonicotinoid seed treatments thiamethoxam (Helix and Helix XTra) and
      clothianidin (Prosper 400) in greenhouse experiments. P. cruciferae experienced
      higher mortality and fed less when exposed to these compounds than did P.
      striolata. Beetles of the overwintered and the summer generations responded
      differently when feeding on seedlings that developed with insecticidal seed
      treatments, with mortality higher for P. cruciferae in May than in August. When
      the two flea beetle species were held together at equal densities and allowed to
      feed on seedlings affected by the seed treatments, mortality of P. cruciferae
      significantly exceeded that of P. striolata. Differences in efficacies of these
      compounds for these beetles have ramifications for management strategies in
      regions where these insects occur sympatrically. Competitive release of P.
      striolata was previously reported to occur when P. cruciferae was excluded from
      brassicaceous crops; consequently, the consistent use of these seed treatments
      over millions of hectares of canola cropland may be a factor that contributes to
      a shift in prevalence of flea beetle pest species from P. cruciferae toward P.
      striolata.

PMID- 18330132
TI  - Baseline susceptibility of tobacco budworm (Lepidoptera: Noctuidae) to Cry1F
      toxin from Bacillus thuringiensis.
AB  - Transgenic cotton, Gossypium hirsutum L., lines expressing both Cry1F and Cry1Ac
      insecticidal proteins from Bacillus thuringiensis (Bt) have been commercially
      available in the United States since 2005. Both Bt proteins are highly effective
      against tobacco budworm, Heliothis virescens (F.), and other lepidopteran pests
      of cotton. Although CrylAc has been available in Bt cotton since 1996, the Cry1F
      component is relatively new. As part of the proactive resistance management
      program for Cry1F/Cry1Ac cotton, a susceptibility-monitoring program is being
      implemented. Baseline variation in the susceptibility to Cry1F in field
      populations of tobacco budworm was measured. There was a three-fold variation in
      the amount of Cry1F needed to kill 50% of the neonates from 15 different field
      populations from the southern and central United States. Future variation in
      susceptibility of tobacco budworm populations to Cry1F or even resistance
      evolution could be documented based on this baseline data. A candidate diagnostic
      concentration was determined that may be efficiently used to identify individuals
      that potentially carry major alleles conferring field-relevant resistance to
      Cry1F before such alleles spread through field populations.

PMID- 18330133
TI  - Baseline susceptibility of Bemisia tabaci B biotype (Hemiptera: Aleyrodidae)
      populations from California and Arizona to spiromesifen.
AB  - Susceptibility to spiromesifen, a tetronic acid derivative, was determined for
      three imidacloprid-resistant strains and 12 geographically discrete natural
      populations of Bemisia tabaci (Gennadius) (=Bemisia argentifolii Bellows &
      Perring) (Hemiptera: Aleyrodidae) from California and Arizona by laboratory
      bioassays. Newly emerged first instars were sprayed with aqueous serial dilutions
      of spiromesifen and evaluated for toxicity to establish baseline susceptibility
      data. Interpopulation variability in susceptibility to spiromesifen was observed
      among the natural populations of whiteflies up to 29-fold; however, there was
      only 30-fold difference in susceptibility among natural and resistant populations
      tested. In general, spiromesifen was quite toxic to first instars across most of
      their geographic range, with LC50 values ranging from 0.210 to 6.08 microg
      (AI)/ml. The magnitude of variation was smaller among the three-resistant
      strains. These results suggest that the observed variability reflect natural
      variation in spiromesifen susceptibility among all the test populations, possibly
      due to previous exposure to insecticides at each location. The effectiveness of
      spiromesifen also was evaluated against all immature stages of whiteflies from
      three field and two resistant strains. Spiromesifen was significantly more active
      against early instars of whiteflies based on lower LC50 values recorded compared
      with the fourth instars. Spiromesifen was effective against the resistant strains
      including a Q-biotype of B. tabaci from Spain, which is highly resistant to
      neonicotinoids. Results of this study indicate absence of cross-resistance
      between spiromesifen and more commonly used neonicotinoids. Our findings suggest
      that spiromesifen should be considered an ideal candidate for whitefly resistance
      management programs in rotation with other effective chemistries.

PMID- 18330134
TI  - Effect of transgenic Bacillus thuringiensis rice lines on mortality and feeding
      behavior of rice stem borers (Lepidoptera: Crambidae).
AB  - Ten transgenic Bacillus thuringiensis Bt rice, Oryza sativa L., lines with
      different Bt genes (two Cry1Ac lines, three Cry2A lines, and five Cry9C lines)
      derived from the same variety Minghui 63 were evaluated in both the laboratory
      and the field. Bioassays were conducted by using the first instars of two main
      rice lepidopteran insect species: yellow stem borer, Scirpophaga incertulas
      (Walker) and Asiatic rice borer, Chilo suppressalis (Walker). All transgenic
      lines exhibited high toxicity to these two rice borers. Field evaluation results
      also showed that all transgenic lines were highly insect resistant with both
      natural infestation and manual infestation of the neonate larvae of S. incertulas
      compared with the nontransformed Minghui63. Bt protein concentrations in leaves
      of 10 transgenic rice lines were estimated by the sandwich enzyme-linked
      immunosorbent assay. The cry9C gene had the highest expression level, next was
      cry2A gene, and the cry1Ac gene expressed at the lowest level. The feeding
      behavior of 7-d-old Asiatic rice borer to three classes of Bt transgenic rice
      lines also was detected by using rice culm cuttings. The results showed that 7-d
      old larvae of Asiatic rice borer have the capacity to distinguish Bt and non-Bt
      culm cuttings and preferentially fed on non-Bt cuttings. When only Bt culm
      cuttings with three classes of different Bt proteins (CrylAc, Cry2A, and Cry9C)
      were fed, significant distribution difference of 7-d-old Asiatic rice borer in
      culm cuttings of different Bt proteins also was found. In the current study, we
      evaluate different Bt genes in the same rice variety in both the laboratory and
      the field, and also tested feeding behavior of rice insect to these Bt rice.
      These data are valuable for the further development of two-toxin Bt rice and
      establishment of appropriate insect resistance management in the future.

PMID- 18330135
TI  - Population genetic structure of codling moth (Lepidoptera: Tortricidae) from
      apple orchards in central Chile.
AB  - Codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), is the main pest
      of pome fruits worldwide. Despite its economic importance, little is known about
      the genetic structure and patterns of dispersal at the local and regional scale,
      which are important aspects for establishing a control strategy for this pest. An
      analysis of genetic variability using microsatellites was performed for 11
      codling moth populations in the two major apple (Malus domestica Borkh) cropping
      regions in central Chile. Despite the geographical distances between some
      populations (approximately 185 km), there was low genetic differentiation among
      populations (F(ST) = 0.002176), with only slight isolation by distance. Only
      approximately 0.2% of the genetic variability was found among the populations.
      Geographically structured genetic variation was independent of apple orchard
      management (production or abandoned). These results suggest a high genetic
      exchange of codling moth between orchards, possibly mediated by human activities
      related to fruit production.

PMID- 18330136
TI  - Screening hybrid poplar clones for susceptibility to Cryptorhynchus lapathi
      (Coleoptera: Curculionidae).
AB  - The poplar-and-willow borer, Cryptorhynchus lapathi (L.) (Coleoptera:
      Curculionidae), is a wood-boring pest of economic importance in irrigated hybrid
      poplar (Populus spp.) farms in eastern Washington and Oregon. There is no
      practical insecticide control tactic against either the larval or adult stage of
      C. lapathi. To assess variability in C. lapathi toward clone preference, we
      initiated a no-choice study on 180 caged trees that consisted of five clones in a
      randomized complete block design. C. lapathi was significantly more successful at
      establishing a population in two clones with Populus trichocarpa X P. deltoides
      (TxD) parentage (female x male) than in either of two clones with P. deltoides x
      P. nigra (DxN) parentage (female x male), or a single clone with P. deltoides x
      P. maximowiczii (DxM) parentage (female X male). There were no significant
      differences in the rate of weevil development among infested clones, with the
      exception of DxM trees. Larvae in DxM clones developed on average to the fourth
      size grouping and those in the two TxD clones developed on average to the fifth
      size grouping, and this difference was significant. These results corroborate our
      general damage surveys conducted in the field. Our findings provide growers with
      the option to choose less susceptible varieties when replanting.

PMID- 18330137
TI  - Susceptibility of fruit from diverse apple and crabapple germplasm to attack from
      apple maggot (Diptera: Tephritidae).
AB  - Apple maggot, Rhagoletis pomonella (Walsh) (Diptera: Tephritidae), is a pest of
      major concern to apple, Malus x domestica (Borkh.) production in eastern North
      America. Host plant resistance to apple maggot among apple germplasm has been
      previously evaluated among a small number of exotic Malus accessions and domestic
      hybrid selections. However, a large number of exotic accessions housed in USDA
      collections have never been evaluated for their susceptibility to apple pests.
      Additionally, previous reports of resistance need to be confirmed under both
      field conditions and with more rigorous laboratory evaluations. Thus, studies
      were conducted to evaluate the susceptibility of a number of Malus accessions
      housed at the USDA Plant Genetic Resources Unit "core" collection. Contrary to
      earlier published reports, these results suggest that some selections previously
      described as "resistant" are in fact susceptible to both oviposition damage and
      larval feeding damage by apple maggot. One domestic, disease-resistant apple
      accession, 'E36-7' is resistant to survival of apple maggot larvae except when
      the fruit is nearly ripe in late fall. This is the first report of an apple
      cultivar that is confirmed to be resistant to larval feeding of apple maggot.
      Although adults can successfully oviposit on all accessions examined, larval
      survival was zero in a number of small-fruited crabapple accessions classified as
      resistant in previous studies and also in two accessions, Malus tschonoskii
      (Maxim) C. K. Schneid. and M. spectabilis (Aiton) Borkh., that have not been
      previously evaluated.

PMID- 18330138
TI  - Determination of Oebalus pugnax (Hemiptera: Pentatomidae) spatial pattern in rice
      and development of visual sampling methods and population sampling plans.
AB  - Commercial rice, Oryza sativa L., fields in southeastern Texas were sampled
      during 2003 and 2004, and visual samples were compared with sweep net samples.
      Fields were sampled at different stages of panicle development, times of day, and
      by different operators. Significant differences were found between perimeter and
      within field sweep net samples, indicating that samples taken 9 m from the field
      margin overestimate within field Oebalus pugnax (F.) (Hemiptera: Pentatomidae)
      populations. Time of day did not significantly affect the number of O. pugnax
      caught with the sweep net; however, there was a trend to capture more insects
      during morning than afternoon. For all sampling methods evaluated during this
      study, O. pugnax was found to have an aggregated spatial pattern at most
      densities. When comparing sweep net with visual sampling methods, one sweep of
      the "long stick" and two sweeps of the "sweep stick" correlated well with the
      sweep net (r2 = 0.639 and r2 = 0.815, respectively). This relationship was not
      affected by time of day of sampling, stage of panicle development, type of
      planting or operator. Relative cost-reliability, which incorporates probability
      of adoption, indicates the visual methods are more cost-reliable than the sweep
      net for sampling O.

PMID- 18330139
TI  - Comparison of sampling methods for determining relative densities of Homalodisca
      vitripennis (Hemiptera: Cicadellidae) on citrus.
AB  - Four sampling methods that included A-Vac, D-Vac, pole-bucket, and beat-net
      devices were evaluated for estimating relative densities of glassy-winged
      sharpshooter, Homalodisca vitri-pennis (Germar) (Hemiptera: Cicadellidae) nymphs
      and adults on citrus (Citrus spp.) trees. All four methods produced similar
      temporal and spatial distribution profiles, although significant differences in
      quantities of H. vitripennis adults and nymphs caught by each device were
      observed. The four sampling methods also showed a consistent male bias in adult
      populations across a range of densities, suggesting that previously reported male
      biased sex ratios in H. vitripennis adult populations are real and not a product
      of sampling bias. A strong relationship (R2 = 0.95) between the monitoring
      methods we evaluated and yellow sticky trap catches of female H. vitripennis
      adults suggest that yellow sticky trap catches may provide a good relative index
      of infestation levels in citrus trees. Based on quantitative analyses examining
      precision and cost, the pole bucket was the most efficient method for sampling
      nymphs, and it was as efficient as the beat-net method for sampling adults and
      both stages combined. In addition to these analyses, consideration of other
      sampling characteristics such as added flexibility in sampling and higher
      sensitivity in detecting infestations within individual trees helped to fortify
      the conclusion that the pole bucket was the best overall sampling method of those
      tested.

PMID- 18330140
TI  - Protein and amino acid requirements in human nutrition.
AB  - The World Health Organization and the Food and Agriculture Organization have
      worked to quantify the energy and nutrient needs of populations since 1949. This
      is the latest in a series of reports that aim to provide: updates on protein and
      amino acid requirements in health and disease for all age groups and pregnant and
      lactating mothers; recommendations on protein requirements in health and disease,
      including their implications for developing countries; recommendations on protein
      quality and labelling for worldwide use. This report provides the tools to
      address practical questions on the adequacy of food supplies, targets for food
      and nutrition policy, and labelling of protein quality. It contains specific
      recommendations for infant, child and adult nutrition. This report is an
      essential reference for those who need to determine the adequacy of population
      food intakes; set national food and nutrition guidelines and regulations on the
      protein and amino acid content of industrially processed foods; determine
      nutrient needs, and evaluate and ensure the adequacy of rations for vulnerable
      groups. The tools in this report can also be used to map and monitor global food
      shortages and under-nutrition through early warning systems.

PMID- 18330141
TI  - CNT based actuators: experimental and theoretical investigation of the in-plain
      strain generation.
AB  - Actuators based on carbon nanotubes (CNT) have the potential to generate high
      forces at very low voltages. The density of the raw material is just 1330 kg/m3,
      which makes them well applicable for lightweight applications. Moreover, active
      strains of up to 1% can be achieved-due to the CNTs dimensional changes on charge
      injection. Therefore the nanotubes have to be arranged and electrically wired
      like electrodes of a capacitor. Immersing the nanotubes in an electrolyte
      increases the capacity of the system by allowing electro-chemical double layers
      to be built around the CNT. For the experimental investigation of the strain
      generation, carbon nanotube sheets are manufactured by vacuum filtration. The in
      plain strain response is being examined, when applying a voltage to the system.
      This paper presents experimental investigations of the systems response in
      dependence of varying system parameters like capacity and resistance.
      Dependencies of the actuator system were formulated from these experimental
      results. A guideline of how to improve a CNT based actuator is derived from these
      dependencies.

PMID- 18330142
TI  - Fabrication of a gold nanoparticles decorated carbon nanotubes based novel
      modified electrode for the electrochemical detection of glucose.
AB  - A modified electrode based on gold nanoparticles decorated multiwall carbon
      nanotubes (MWNTs), MWNT-Au(nano)-ME is fabricated. MWNTs are functionalized with
      4-aminothiophenol and coated over the glassy carbon electrode. Further, Au
      nanoparticles are deposited into MWNTs coated GC electrode by electrochemical
      reduction of HAuCl4. Field emission transmission electron microscope (FETEM)
      image shows the formation of approximately 5 nm sized Au nanoparticles without
      any agglomeration on the MWNTs surface. Further, the presence of Au nanoparticles
      is confirmed through X-ray photoelectron spectroscopic (XPS) studies. The
      electrocatalytic activity of the MWNT-Au(nano)-ME towards the detection of
      glucose is investigated. MWNT-Au(nano)-ME shows enhanced current response than
      pristine MWNT-ME over the entire (+0.05 to +0.80 V) potential range. The modified
      electrode shows linear response to current with the concentration of glucose
      between 1 and 20 mM. Larger current responses to glucose oxidation are witnessed
      at +0.60 V than at +0.05 V. However, a large interference signal, reflecting the
      accelerated oxidation of electroactive interference is observed at +0.60 V. No
      overlapping signal from the interferents such as ascorbic acid, acetaminophen,
      and dopamine are observed at the MWNT-Au(nano)-ME at +0.05 V. Further, the MWNT
      Au(nano)-ME shows high resistance to the toxictiy of chloride ions.

PMID- 18330143
TI  - Carbon nanotube fiber microelectrodes: design, characterization, and
      optimization.
AB  - We report on the preparation and interesting electrochemical behavior of carbon
      nanotube fiber microelectrodes (CNTFM). By combining the advantages of carbon
      nanotubes (CNT) with those of fiber electrodes, this type of microelectrode
      differs from CNT modified or CNT containing composite electrodes, because it's
      made of only CNT without any other components like additives or binders. The
      active CNT surface is easily regenerated. The performance of CNTFMs has been
      characterized, among others, by surface modification with phosphomolybdic acid.
      It is shown that adsorption behavior of these catalyst molecules is highly
      improved with a controlled orientation of CNT. A better CNT alignment inside the
      fiber can be achieved by a hot stretching procedure.

PMID- 18330144
TI  - Dispersions of functionalized single-walled carbon nanotubes in strong acids:
      solubility and rheology.
AB  - The manipulation and processing of single-wall carbon nanotubes (SWNTs) is
      limited by their poor solubility in most common solvents. Covalent sidewall
      functionalization of SWNTs provides an excellent route to improve their
      solubility. Here we have studied the relationship between sidewall
      functionalization and phase behavior of solutions of functionalized SWNTs (f
      SWNTs) in strong acids. We use centrifugation in conjunction with UV-Vis-nlR
      spectroscopy to quantify the solubility of f-SWNTs in strong acids. We image the
      dispersions of functionalized tubes by polarized light microscopy. We find that
      adding butyl groups increases marginally the solubility of SWNTs in 102% sulfuric
      acid in the isotropic phase; adding 9-nonadecyne groups roughly doubles the
      solubility of SWNTs. Viscosity measurements in dilute solutions are sensitive to
      de-bundling. We compare the viscosity-concentration dependence of dilute pristine
      and f-SWNTs to assess whether and how functionalization promotes de-bundling and
      stabilizes the tubes. The phase behavior and rheology of these f-SWNTs parallels
      with that of pristine SWNTs; 9-nonadecylated SWNTs have higher solubility and
      should be easier to process.

PMID- 18330145
TI  - Synthesis and characterization of processable multi-walled carbon nanotubes
      sulfonated polydiphenylamine graft copolymers.
AB  - Water soluble and processable nanocomposites composed of multi-walled carbon
      nanotubes (MWNTs) and poly(diphenylamine sulfonic acid) (PDPASA) are synthesized
      and characterized. Two types of methodologies are adopted. MWNTs are covalently
      functionalized with 2,5-diaminobenzene sulfonic acid (DABSA) and further in situ
      polymerized with diphenylamine-4-sulfonic acid (DPASA). This results in the
      formation of nanocomposites, MWNT(DABSA)-g-PDPASA, in which PDPASA is presented
      as the graft chains onto MWNTs. In another approach, DPASA is in situ polymerized
      in presence of unfunctionalized MWNTs, results in a nanocomposite in which MWNTs
      are present as entrapped mass in PDPASA matrix. Both nanocomposites are found to
      be water soluble and can form free standing films. The conductivity of
      MWNT(DABSA)-g-PDPASA and MWNT/PDPASA is found to be 1.25 mS x cm(-1) and 0.65 mS
      x cm(-1), respectively, which is higher than that of pristine PDPASA (0.25 x 10(
      5) S x cm(-1)). The nanocomposites are characterized for their structure,
      morphology, optical and thermal properties.

PMID- 18330146
TI  - Ultra-high oxidation resistance of suspended single-wall carbon nanotube bundles
      grown by an "all-laser" process.
AB  - Single-wall carbon nanotubes (SWCNTs) were laterally grown on SiO2/Si substrates
      by means of an "all-laser" growth process. Our "all-laser" process stands out by
      its exclusive use of the same pulsed UV laser, first, to deposit the CoNi
      nanocatalyst and, second, to grow SWCNTs through the laser ablation of a pure
      graphite target. The "all-laser" grown SWCNTs generally self-assemble into
      bundles (5-15 nm-diam.) sprouting from the CoNi nanocatalyst and laterally
      bridging the 2 microm gap separating adjacent catalysed electrodes (in either
      "suspended" or "on-substrate" geometries). A comparative study of the oxidation
      resistance of both suspended and on-substrate SWCNTs was achieved. The "all
      laser" grown SWCNTs were subjected to annealing under flowing oxygen at
      temperatures ranging from 200 to 1100 degrees C. Systematic scanning electron
      microscopy observations combined with micro-Raman analyses revealed that more
      than 20% of suspended nanotubes were still stable at temperatures as high as 900
      degrees C under flowing O2 while the on-substrate counterpart were completely
      burnt out at this temperature. Accordingly, the activation energy, as deduced
      from the Arrhenius plot, of the suspended SWCNTs is found to be as high as
      approximately 180 kJ mol(-1) (approximately 9 times higher than that of the on
      substrate ones). The high quality (almost defect-free) of the nanotubes
      synthesized by the "all-laser" approach, their protected tips into the embedded
      CoNi catalyst nanolayer together with their suspended geometry are thought to be
      responsible for their unprecedented ultra-high oxidation resistance. This opens
      up new prospects for the use of these suspended nanotubes into nanodevices that
      have to operate under highly oxidizing environments.

PMID- 18330147
TI  - Multi-walled carbon nanotube/polystyrene composites prepared by in-situ bulk
      sonochemical polymerization.
AB  - Nanocomposites with multi-walled carbon nanotubes (MWNT) and polystyrene (PS)
      were synthesized via an in-situ bulk sonochemical polymerization under the
      application of ultrasonication to open pi-bonds in the MWNT, thus enhancing the
      PS polymerization. Sonication of vinyl monomers such as styrene leads to radical
      initiation of polymerization. Various characteristics such as morphology, thermal
      property of the synthesized PS in the presence of the MWNT in the PS/MWNT
      composites were examined by SEM, TEM, thermogravimetric analysis, respectively.
      Their rheological properties were also investigated using a stress-controlled
      rotational rheometer under small amplitude oscillation and steady transient shear
      in their melt state.

PMID- 18330148
TI  - Formation of an adherent polyacrylonitrile/carbon nanotubes composite film onto a
      polyacrylonitrile brush electrografted on copper.
AB  - An adherent polymer film based on a composite of polyacrylonitrile/multiwall
      carbon nanotubes (PAN/MWNTs) have been elaborated on a copper substrate. The
      first layer is an electrografted PAN brush on which of a subsequent layer of
      PAN/carbon nanotubes composite has been deposited by simple dipping from solution
      in dimethylformamide (DMF). MWNTs have been previously chemically functionalized
      with 3-cyanopropyltrichlorosilane to promote de-bundling and homogeneous
      dispersion of the carbon nanotubes in the composite.

PMID- 18330149
TI  - Note on the dispersion in perfluoropolyether lubricants of multi-walled carbon
      nanotubes functionalized with (tridecafluoro-1,1 ,2,2
      tetrahydrooctyl)trichlorosilane.
AB  - Multi-walled carbon nanotubes functionalized with F3C-(CF2)5-(CH2)2-SiCl3, a
      molecule bearing a fluorinated terminal group is found to favor the carbon
      nanotubes dispersion in three perfluoropolyether fluids (Galden SV70, Fomblin Y25
      and Fomblin YR1800). The stability of the suspension appears to be related to the
      perfluoropolyether viscosity. With respect to time, Fomblin YR1800, the more
      viscous fluid, leads to the most stable solutions, followed in order by Fomblin
      Y25 and Galden SV70. In general the smallest particles stay in suspensions.
      Stability extending over more than one year is observed in the case of Fomblin
      YR1800.

PMID- 18330150
TI  - Dislocations in carbon nanotube walls.
AB  - We present a novel interpretation of defected tubes based on a dislocation model.
      A scroll (a sheet rolled without closure) is considered as an axial edge
      dislocation in a multiwall nanotube (MWNT). Screw dislocation type defects
      separate scroll from nested-tubes within the same nanotube. The glide of the
      screw dislocation causes the transformation between these two forms. In some
      cases, the mechanism of formation of an MWNT could, therefore, start with the
      formation of a scroll which, by gliding of a screw dislocation, is transformed
      into the more stable MWNT We compare the structure and energetics of prismatic
      screw and edge dislocations in graphite and carbon nanotubes. We present
      calculations for the Peierls barrier of the first kind for graphite and we
      discuss this result for glide motion of screw dislocations in nanotubes. There is
      no evidence for stable sp3 atoms in any of the studied nanostructures.

PMID- 18330151
TI  - Decarboxylation of oxidized single-wall carbon nanotubes.
AB  - A classical protocol widely used in organic chemistry of aromatic and
      polyaromatic molecules has been successfully applied in this work for the
      decarboxylation of oxidized single-wall carbon nanotube (SWNT) to rend C-H SWNT
      derivatives. SWNT produced by arc discharge method have been oxidized during a
      purification process using strongly oxidant agents, such as hydrogen peroxide and
      nitric acid. The decarboxylation of oxidized SWNT has been conduced with
      copper(I) oxide in a 50:50 solution of N-methylpyrrolidone and quinoline. Fourier
      transform infrared spectroscopy, X-ray photoelectron spectroscopy and acid-base
      potentiometric titration analyses were carried out to characterize quali and
      quantitatively the changes in the chemical environment on the SWNT surface in
      each step of the purification and the decarboxylation process. Those techniques
      showed the appearance of mainly carboxylic and phenolic groups after the
      purification process and the disappearance of the carboxylic groups after the
      decarboxylation reaction. Fourier transform infrared spectroscopy analysis
      indicated also the formation of aliphatic and aromatic C-H groups. X-ray
      photoelectron spectroscopy and potentiometric titration results determined an
      efficiency higher than 90% for our decarboxylation procedure. The purity and
      structural quality of the SWNT sample used in the decarboxylation process were
      evaluated by thermogravimetry and Raman spectroscopy. Thermogravimetric analysis
      identified a purified sample with approximately 80 wt% of SWNT, in fractions
      distributed in highly structured SWNTs (25 wt%), with distribution in
      composition, length and structural quality (35 wt%) and with very defective and
      short tubes (25 wt%). The damages on the purified SWNT walls were characterized
      by the Raman scattering analysis.

PMID- 18330152
TI  - Dielectrophoresis-induced separation of metallic and semiconducting single-wall
      carbon nanotubes in a continuous flow microfluidic system.
AB  - The AC dielectrophoresis-induced separation of metallic and semiconducting single
      wall carbon nanotubes has been carried out in a continuous flow microfluidic
      system with isolated electrodes. The separation has been studied for single-wall
      carbon nanotube aqueous suspensions with ionic (sodium dodecylsulphate) and non
      ionic (TritonX-100) surfactants. The efficiency of separation has been determined
      with the help of resonant Raman spectroscopy using various excitation energies.
      The prototype microfluidic cell presently shows somewhat inferior separation
      efficiency with respect to static dielectrophoretic filtering on arrays of
      microelectrodes but has potential for improvements. Factors influencing the
      separation efficiency and scaling up of the process are discussed.

PMID- 18330153
TI  - Solubilization of single-wall carbon nanotubes in Organic solvents without
      sidewall functionalization.
AB  - Single walled carbon nanotubes (SWNTs) may be made soluble in a range of organic
      solvents without sidewall functionalization via their reduction by Na/Hg amalgam
      in the presence of dibenzo-18-crown-6. The [Na(dibenzo-18-crown-6)]n[SWNT]
      complex has been characterized by UV-Visible, Raman, and AFM and is consistent
      with no additional sidewall functionalization as compared with raw SWNTs, while
      MALDI-MS shows the presence of the [Na(dibenzo-18-crown-6)]+ ion. Solubility is
      greatest in CH2Cl2 and DMF being comparable to surfactant dispersed SWNTs,
      however, measurable solubilities are also observed in hexane, toluene, and
      alcohols. Reaction with alkyl halides (bromohexane, 1-iodododecane) yields alkyl
      functionalized SWNTs (i.e., C6H11-SWNTs and C12H25-SWNTs) with an C(SWNT):alkyl
      ratio (ca. 40:1) significantly lower than that observed by the analogous reaction
      of alkyl halides with reduced SWNTs formed by the Billups method in liquid
      ammonia.

PMID- 18330154
TI  - The 1,3-dipolar cycloaddition reaction in the functionalization of carbon
      nanofibers.
AB  - Carbon nanofibers were functionalized using a reaction scheme described in the
      literature for 1,3-dipolar cycloaddition of azomethine ylides generated in situ
      by the condensation of an alpha-amino acid and an aldehyde. The reagents used
      were Z-Gly-OH and paraformaldehyde. Their reaction with carbon nanofibers was
      studied as a solid mixture by controlled heating in the DSC. An oxazolidinone
      intermediate was formed as the major product. Z-Gly-OH and paraformaldehyde were
      also reacted with a model compound (anthracene) in DMF solution leading to the
      formation of a considerable amount of anthraquinone. These studies suggested
      that, under the conditions investigated, the 1,3-dipolar cycloaddition reaction
      was not favoured, and the main result of functionalization was the formation of
      quinone-type groups as a consequence of an oxidation process.

PMID- 18330155
TI  - Modeling the effect of dispersed doping agents in carbon nanotubes.
AB  - Theoretical studies of how the electronic properties of a nanotube are affected
      by one isolated doping agent is commonly done by ab-initio electronic structure
      calculations. Although these calculations are essential to understand how the
      system responds to doping, they are by no means sufficient, since, in reality, a
      large disordered array of doping agents must be considered. It is then necessary
      to combine ab-initio techniques with less-computationally-demanding methods if
      one wishes to describe the real effect of doping on the electronic properties of
      nanotubes. Here we propose a method that makes use of ab-initio results for
      single impurities as an input to generate the parameters of the less-demanding
      tight-binding technique. The method is based on suitable sum rules for the Green
      functions of the impurity-free nanotubes and does not rely on any fitting scheme.
      The resulting parametrization allows us to describe disordered systems without
      losing the important contributions due to charge transfer and screening.
      Transport properties are subsequentially investigated.

PMID- 18330156
TI  - Grafting of polystyrene on nitrogen-doped multi-walled carbon nanotubes.
AB  - Polymer grafting of polystyrene (PS) on nitrogen-doped multiwall carbon nanotubes
      (CNx) was successfully obtained by a "grafting from" technique. The production
      method involves the immobilization of initiators, using wet chemistry, onto the
      nanotube surface, followed by an in situ surface-initiated polymerization. The
      polymer-grafting carbon nanotubes synthesis includes the free radical
      functionalization of CNx and the "controlled/living" Nitroxide Mediated Radical
      Polymerization (NMRP). The obtained products were studied using several
      microscopic techniques as scanning electron microscopy (SEM), high-resolution
      transmission electron microscopy (HRTEM), and electron energy loss spectroscopy
      (EELS). The characterization also includes thermogravimetric analysis (TGA),
      Raman spectroscopy, infrared spectroscopy, and electron spin resonance (ESR),
      among others. The analyzed samples were also compared with solutions fabricated
      by physical blending of the polymer and CNx nanotubes. These results indicate
      that the nanotube radical functionalization, the chemical grafting, and the
      polymerization reaction were obtained over CNx when NMRP method was successfully
      used, giving rise to a uniform PS layer of several nanometers grafted on the
      outer surface of the CNx nanotubes. Several properties of the PS-grafted CNx
      nanotubes were also studied. It is shown that the production method leads to a
      narrower distribution of the external diameters. Moreover, their solubilization
      in organic solvents is greatly improved. Finally, the dispersion of PS-grafted
      CNx into a PS matrix is studied to determine the differences in filler dispersion
      and interfacial adhesion strength, in comparison with nanocomposites elaborated
      with as-produced CNx.

PMID- 18330157
TI  - Dispersion study of long and aligned multi-walled carbon nanotubes in water.
AB  - Dispersion of nanotubes is a crucial step for many applications. The properties
      of the final nanotube-based material are strongly dependent on the quality of
      nanotube suspensions. In this study, long and aligned multi-walled carbon
      nanotubes obtained by catalytic chemical vapour deposition were dispersed in
      water with different dispersing agents using high intensity ultrasounds. Among
      different additives, we selected sodium dodecyl sulfate (SDS) as dispersing agent
      to prepare suspensions of nanotubes. UV-Visible spectrometry method was used to
      measure the influence of dispersion parameters (power and duration of sonication)
      on dispersion state and suspension stability. Therefore, we demonstrated that,
      even if high intensity ultra-sounds are breaking nanotubes, it is possible to
      obtain stable water-based suspensions containing MWNTs which exhibit length up to
      20 microm.

PMID- 18330158
TI  - NEXAFS study of multi-walled carbon nanotubes functionalization with sulfonated
      poly(ether ether ketone) chains.
AB  - Functionalization of multi-walled carbon nanotubes (MWNTs) surface by sulfonated
      poly (ether ether ketone) SPEEK chains using a direct attachment reaction was
      investigated. A two step method was performed. MWNTs were oxidized by a nitric
      acid treatment to generate carboxyl groups on their surface. The grafting
      reaction of sulfonated groups of SPEEK with carboxyl groups present on the
      surface of oxidized MWNTs readily proceeds by using hexane diamine as an
      interlinking molecule. Transmission electron microscopy (TEM) shows that tubes
      are wrapped by polymer chains. Near edge X-ray absorption fine structure
      spectroscopy (NEXAFS) at the C K-edge, O K-edge, and N K-edge and X-ray
      photoelectron spectroscopy (XPS) were used to give evidence of covalent
      functionalization of MWNTs by SPEEK macromolecules.

PMID- 18330159
TI  - Soluble functionalized carbon nanohorns.
AB  - Carbon nanahorns (CNH) were functionalized following the methodology of 1,3
      dipolar cycloaddition of azomethine ylides and found to form stable solutions in
      either organic solvents or water. The number of added functional units, in the
      form of pyrrolidine moieties, was calculated when a pyrene chromophore was
      utilized in the modification scheme. Moreover, complementary theoretical
      calculations revealed that reactivity enhancement is expected at locations near
      the conical-shaped tip of CNH, where the highest curvature and strain exist.
      Finally, additional organic transformation of already modified CNH was exploited
      by covalently linked ferrocene units.

PMID- 18330160
TI  - FTIR and thermogravimetric analysis of biotin-functionalized single-walled carbon
      nanotubes.
AB  - We report the covalent functionalization of single-walled carbon nanotubes
      (SWNTs) with biotin. The synthesized functionalized SWNT materials were fully
      characterized by FTIR and thermogravimetric analysis. These characterization
      techniques provided valuable information concerning the nature of the obtained
      SWNT materials as well as the efficiency of the employed synthetic route towards
      SWNT covalent functionalization with biotin.

PMID- 18330161
TI  - Purity evaluation of carbon nanotube materials by thermogravimetric, TEM, and SEM
      methods.
AB  - Raw and purified samples of carbon nanotubes are considered as multicomponent
      systems with a distribution of carbonaceous, amorphous, multishell graphitic
      particles and nanotubes, together with the particles of metal compounds from the
      catalyst. With respect to the carbon nanotube fractions, a distribution of size,
      defect concentrations, and functionalities needs to be taken into account. In
      order to address the problem of quantitative evaluation of purity it is necessary
      to measure the quality and distribution of the carbon nanotubes. In this research
      conventional and high resolution thermogravimetry are applied to quantify
      different fractions of carbonaceous and metallic materials in raw and moderately
      purified single walled and multiwalled carbon nanotubes. For each oxidized
      fraction, defined by careful line shape analysis of the derivative
      thermogravimetric curves (DTG), the temperature of maximum rate of oxidation, the
      temperature range for this oxidation, related to the degree of homogeneity, and
      the amount of associated material is specified. The attribution of carbonaceous
      materials to each fraction in the distribution was based on SEM and TEM
      measurements and the literature. The MWNT purified sample with 1.6 wt% metal
      oxide was investigated by high resolution thermogravimetry (HRTG). The
      quantitative assessment for the carbonaceous fractions was 25 wt% of amorphous
      and high defect carbonaceous materials including nanotubes, 54 wt% MWNT and 20
      wt% multishell graphitic particles. A qualitative evaluation of these fractions
      was obtained from the SEM and TEM images and supports these results. The accuracy
      of the values, taking into account other measurements performed on the same batch
      of material, should be more sensible than +/-4 wt%.

PMID- 18330162
TI  - Electrodeposition and characterisation of polypyrroles containing sulfonated
      carbon nanotubes.
AB  - Using facile diazonium chemistry, sulfonate groups have been covalently attached
      to single wall carbon nanotubes. The resulting sulfonated tubes form a stable
      aqueous dispersion in the presence of pyrrole monomer. Subsequent
      electropolymerisation results in a conductive, electroactive polypyrrole doped
      with sulfonated tubes being formed at unusually low potentials. The potential of
      this material as a host matrix for biomolecules has been demonstrated by
      entrapping horse-radish peroxidase directly in the polypyrrole during composite
      formation.

PMID- 18330163
TI  - A novel catalyst for synthesis of styrene: carbon nanofibers immobilized on
      activated carbon.
AB  - Carbon NanoFibers (CNFs) with hierarchically structure have been immobilized onto
      Activated Carbon (AC) by impregnation with an aqueous solution of Fe(CH3COO)2,
      reduction and subsequent chemical vapor decomposition of ethylene. The morphology
      of the CNFs can be modulated by adjusting the pH of the Fe(CH3COO)2 solution used
      for impregnating the AC. A stable yield of 35% in the oxidative dehydrogenation
      of ethylbenzene to styrene was obtained at a temperature of 673 K, around 200 K
      lower than the current industrial process. The immobilized CNFs on AC catalysts
      combine the catalytic properties of the carbon nanofibers and the suprastructure
      of the AC host. The final material is an easy to handle active catalyst, with an
      open structure of immobilized CNFs avoiding the pressure drop problem, which is
      typically observed for fine powder forms of CNFs. The immobilized CNFs on AC are
      attractive for gas-phase fixed-bed industrial applications.

PMID- 18330164
TI  - The influence of the reaction temperature on the morphology of sodium titanate 1D
      nanostructures and their thermal stability.
AB  - We have synthesized large quantities of sodium-titanate-based nanotubes and
      nanoribbons with high yields under hydrothermal conditions from anatase powder in
      an aqueous NaOH solution. The reaction temperatures were from 95 to 195 degrees
      C, in steps of 20 degrees C. We observed that the morphology of the
      nanomaterials, which is reflected in their specific surface areas, depends
      strongly on the reaction temperature. For the materials synthesized in the range
      95-135 degrees C and above 155 degrees C only a single morphology type was
      observed for the nanostructures, i.e., nanotubes and nanoribbons, respectively.
      In contrast, when the reaction was carried out at 155 degreesC, both nanotubes
      and nanoribbons were found in the product. SEM, TEM, and XRD techniques were used
      to determine the materials' morphological and structural properties, and the
      thermal stability of the materials was investigated with TGA and DSC. The largest
      weight loss, of approximately 25%, was observed in a temperature range from 25 up
      to 600 degrees C for the product obtained at 95 degrees C, probably due to the
      presence of unrolled titanate sheets.

PMID- 18330165
TI  - Covalent functionalization of carbon nanotubes through organometallic reduction
      and electrophilic attack.
AB  - Organometallic reagents such as butyllithium are known to covalently
      functionalize the sidewalls of carbon nanotubes. The function grafted corresponds
      to the organic part of the alkali compound, while one negative charge is
      transferred to the nanotube for each function. Carbon nanotubes reduced by
      organolithium compounds were used here as nucleophilic reactive species through
      these transferred and delocalized charges. Various halogenated electrophiles in
      excess were reacted with them in anhydrous conditions. The grafting of the
      corresponding chemical function onto the carbon nanotubes through a Lewis
      metathetic exchange reaction was demonstrated by chemical, thermal, and
      spectroscopic analyses. This synthetic route applied successfully to both single
      walled and multi-walled nanotubes and to a series of electrophiles. The extent of
      functionalization was found to depend on stoechiometries used, although a direct
      correlation could not be obtained.

PMID- 18330166
TI  - Functionalization of carbon nanofibers by a Diels-Alder addition reaction.
AB  - This paper reports functionalization of CNF via a Diels-Alder addition reaction
      and the characterization of the obtained materials. The functionalization was
      assessed by a calorimetric technique (DSC) and the morphology of CNF modified
      materials was characterized by scanning electron microscopy (SEM) and
      transmission electron microscopy (TEM). The functionalization was observed to be
      dependent on the preparative conditions. Detailed analysis of the CNF modified
      material surface using TEM, shows a deposited layer homogeneously distributed
      over the CNF structures with an average thickness of about 15 nm. Finally the
      chemical activity of the raw CNF and functionalized CNF was analyzed to determine
      the pH of the point of zero charge (pHpzc) values. The results obtained showed
      that the functionalized CNF materials presented enhanced acid activity
      comparatively with the modified carbonaceous materials reported in literature.

PMID- 18330167
TI  - Microwave-assisted functionalization of single-wall carbon nanotubes through
      diazonium.
AB  - Single-wall carbon nanotubes (SWNTs) have been functionalized by a diazonium
      method through both a classical thermal reaction and a microwave-assisted
      reaction. The functionalized SWNTs have been characterized by nIR-Vis-UV
      absorption spectroscopy, Raman spectroscopy, and thermal gravimetric analysis.
      The results show that SWNTs are covalently functionalized through both reactions
      and that the microwave-assisted reaction is more rapid. Moreover, optimal choice
      of the reaction time can prevent the microwave irradiation from the adverse
      effect of subsequently removing the functional groups on the SWNT surface.

PMID- 18330168
TI  - Spectroscopic study of nitrogen doping of multi-walled carbon nanotubes.
AB  - Combined spatially resolved electron-energy loss spectroscopy (EELS) and high
      resolution near-edge X-ray absorption fine structure (NEXAFS) spectroscopy have
      been used to investigate the nitrogen doping of multi-walled carbon nanotubes (N
      MWNT). EELS indicates that most of the tubes are nitrogen-doped. NEXAFS
      spectroscopy reveals pyridine-like and nitrile N structures. High resolution
      NEXAFS experiments show that the main nitrogen concentration originates from a
      high amount of molecular N2 encapsulated into only a small quantity of tubes.

PMID- 18330169
TI  - Purification of single-walled boron nitride nanotubes and boron nitride cages.
AB  - Continuous laser vaporization of a BN target under N2 atmosphere is up to now the
      unique route to single-walled boron nitride nanotubes (BN-SWNTs). Although grams
      of product can be obtained by this technique, the raw material contains in
      addition to the BN-SWNTs, different by-products made of boron and nitrogen. Since
      these materials are undesirable for the studying of the intrinsic properties of
      the nanotubes, we have undertaken a purification process using chemical and
      physical methods to separate the different components. We show here that most
      impurities can be removed by successive cycles of washing, sonication, and
      centrifugation. Furthermore, the two different types of boron nitride
      nanostructures i.e., BN-SWNTs and BN-cages can be isolated. Efficiency of the
      separation was monitored by transmission electron microscopy (TEM) at the
      different steps of the process. Finally, we envisage the further purification of
      the nanotubes-enriched fraction by functionalizing the nanotubes in a non
      covalent manner by specific polymers as for carbon nanotubes and BN multi-walled
      nanotubes.

PMID- 18330170
TI  - Structural study of single-walled carbon nanotube films doped by a solution
      method.
AB  - Herein, we have studied a structure of SWNT films doped by organic molecules. In
      this study, we reacted organic molecules with SWNT films by a vapor phase and a
      liquid phase, respectively. The structure of doped SWNT films was investigated
      using synchrotron X-ray powder diffraction measurements, and we found the clear
      difference between the vapor phase reaction (v-doped) and the liquid phase
      reaction (I-doped). In v-doped SWNT films, organic molecules are predominantly
      encapsulated inside SWNTs, although molecules adsorbed on the surface of SWNT
      bundles in l-doped SWNT films.

PMID- 18330171
TI  - Performance of carbon arc-discharge nanotubes to hydrogen energy storage.
AB  - Adsorption properties of gram-scale samples of different kind of arc discharge
      nanotubes were studied, namely: (A) raw collaret collected on the cathode, (B)
      raw soots collected on the lateral reactor wall, (C) thermally treated soot, and
      (D) thermally then chemically treated soot. The morphology, structure, and
      composition of these materials were characterized by SEM, TEM, TGA, and BET. In
      addition, hydrogen adsorption isotherms were recorded experimentally for A, B,
      and D samples over the pressure range of 0 to 55 bar at ambient temperature. Our
      experiments indicated a maximum-yet weak-hydrogen storage at room temperature of
      approximately 0.13 H2 wt% for the purified product (D).

PMID- 18330172
TI  - Nanoscale surface morphology and monomer concentration dependence on impedance of
      electrocoated 2,2-dimethyl-3,4-propylene-dioxythiophene on carbon fiber
      microelectrode.
AB  - Poly(2,2-Dimethyl-3,4-propylenedioxythiophene) (PProDOT-Me2) thin films have been
      cyclovoltametrically coated onto carbon fiber microelectrode (CFME) as an active
      functionalized microelectrode. An electrochemical impedance spectroscopic study
      on the prepared electrodes is reported in this paper which electropolymerization
      performed under different initial monomer concentrations. The electrochemical
      impedance data fitted to equivalent circuit model, used to find out numerical
      values of the proposed components. Effect of the parameters on the capacitive
      behavior of the (PProDOT-Me2) coated carbon fiber microelectrode and morphology
      of films obtained by AFM and SEM was discussed. Highly porous coating was
      obtained at 100 mV/s scan rate and 10 cycles. EDX and ATR-FTIR results indicated
      the doping of anion of electrolyte due to formation of polaronic and bipolaronic
      sites. The presence of surface functional groups were determined by ATR-FTIR.
      Nanoscale conjugated polymer modified carbon fiber microelectrodes exhibited high
      capacitance of approximately 90 degrees phase angle, and vertical line in Nyquist
      plot. The capacitive behavior of CFME was increased by this very thin film
      coating of PProDOT-Me2. The electroactivity of Poly 2,2-Dimethyl-3,4
      propylenedioxythiophene on the carbon fiber microelectrode open the possibility
      of using these coated electrodes for electrochemical microsupercapacitors and
      biosensor electrodes.

PMID- 18330173
TI  - Role of powder treatment and carbon nanotube dispersion in the fracture
      toughening of plasma-sprayed aluminum oxide-carbon nanotube nanocomposite.
AB  - Al2O3 ceramic reinforced with 4-wt% multiwalled carbon nanotube (CNT) is plasma
      sprayed for improving the fracture toughness of the nanocomposite coating. Two
      different methodologies of CNT addition have been adopted in the powder feedstock
      to assist CNT dispersion in the nano-Al2O3 matrix. First, spray-dried nano-Al2O3
      agglomerates are blended with 4 wt% CNT as powder-feedstock, which is
      subsequently plasma sprayed resulting in the fracture toughness improvement of
      19.9%. Secondly, spray dried composite nano-Al2O3 and 4 wt% CNT powder was used
      as feedstock for attaining improved dispersion of CNTs. Plasma sprayed coating of
      composite spray dried powder resulted in increase of 42.9% in the fracture
      toughness. Coating synthesized from the blended powder displayed impact alignment
      of CNTs along splat interface, and CNTs chain loop structure anchoring the fused
      Al2O3 melt whereas coating synthesized from composite spray dried powder evinced
      anchoring of CNTs in the solid state sintered region and CNT mesh formation.
      Enhanced fracture toughness is attributed to significance of CNT dispersion.

PMID- 18330174
TI  - Cross-linking of C60 films with 1,8-diaminooctane and further decoration with
      silver nanoparticles.
AB  - We applied the direct solvent-free functionalization of fullerene C60 with
      aliphatic bifunctional amine, 1,8-diaminooctane, to prepare chemically cross
      linked C60 thin films capable of binding silver nanoparticles. The gas-phase
      diamine treatment of C60 reduced dramatically the fullerene solubility in
      toluene, indicating the transformation of pristine C60 into a different solid
      phase with cross-linked fullerene molecules. Compared to the spectra of pristine
      C60 film and powder samples, Fourier-transform infrared, UV-Visible, Raman, and
      13C nucleic magnetic resonance spectra of the functionalization products
      exhibited new features, which point to a breaking of C60 ideal structure during
      the formation of new covalent bonds and to the appearance of sp3 hibridization.
      The covalent functionalization with 1,8-diaminooctane allowed for a stable and
      homogeneous deposition of silver nanoparticles of ca. 5-nm diameter onto the
      functionalized films through the coordination bonding between metal atoms and
      nitrogen donor atoms of the fullerene derivatives. The proposed mechanism of Ag
      nanoparticle binding was supported by density functional theory calculations
      using the hybrid BLYP functional in conjunction with the double numerical basis
      set DND.

PMID- 18330175
TI  - DC conductivity and interfacial polarization in PMMA/nanotube and PMMA/soot
      composites.
AB  - This work focuses on the DC conductivity and interfacial polarization of
      poly(methyl methacrylate) (PMMA) composites made with single wall nanotubes
      (SWNTs) and nanotube precursor soot. We aim to compare and contrast the behavior
      of the two nanofillers in an effort to determine if the precursor material
      imparts tunable electrical properties to PMMA. The DC activity of the polymers
      and composites was determined by extrapolating AC conductivity versus frequency
      plots to zero. Activation energies and DC conductivities were obtained through
      Arrhenius plots. The conductivity increased with temperature for all the samples
      in conjunction with viscous flow. Both nanotubes and nanosoot increased the DC
      conductivities. Activation energies for the SWNT decreased slightly upon the
      addition of nanotubes to the matrix. However, the activation energies increased
      with soot content in the matrix, indicating obstruction of motion or possible
      bridging caused by the soot. Cole-Cole plots were effectively used to determine
      the extent of interfacial polarization in the composite samples. Plots shifted
      toward the origin with the addition of carbon nanotubes or with soot
      concentration indicating a Maxwell-Wagner-Sillars process.

PMID- 18330176
TI  - Biodegradable nanocomposites from toughened polyhydroxybutyrate and titanate
      modified montmorillonite clay.
AB  - Montmorillonite clay treated with neopentyl (diallyl)oxy tri(dioctyl)
      pyrophosphato titanate was used as a reinforcement for toughened bacterial
      bioplastic, Polyhydroxybutyrate (PHB) in order to develop novel biodegradable
      nanocomposites. The modified clay, PHB, toughening partner and specific
      compatibilizer were processed by extrusion followed by injection molding.
      Different microscopy and goniometry techniques, rheology analysis, X-ray
      diffraction and thermo-mechanical testing were used to characterize the
      nanocomposites. Results showed that the nanocomposites with 5 wt% titanate
      modified clay loading exhibited about 400% improvement in impact properties and
      40% reduction in modulus in comparison with virgin PHB. The novel aspect of the
      titanate-based modification was that the nanocomposites still maintained nearly
      the same impact strength value as that of toughened PHB. The diffraction patterns
      suggest exfoliation of the organically modified clays and this was further
      supported by transmission electron microscopy and melt rheological analysis. The
      mechanical properties of the nanocomposites were correlated with a modified
      Halpin-Tsai theoretical model and the predictions matched significantly with the
      experimental results. Toughened and compatibilized PHB showed significantly lower
      biodegradation rate than virgin PHB and most significantly the addition of the
      titanate-modified clay in the same formulation enhanced the biodegradation
      several fold.

PMID- 18330177
TI  - Redox protein noncovalent functionalization of double-wall carbon nanotubes:
      electrochemical binder-less glucose biosensor.
AB  - Double wall carbon nanotubes are noncovalently functionalized with redox protein
      and such assembly is used for construction of electrochemical binder-less glucose
      biosensor. Redox protein glucose oxidase performs as biorecognition element and
      double wall carbon nanotubes act both as immobilization platform for redox enzyme
      and as signal transducer. The double carbon nanotubes are characterized by cyclic
      voltammetry and specific surface area measurements; the redox protein
      noncovalently functionalized double wall carbon nanotubes are characterized in
      detail by X-ray photoelectron spectroscopy, cyclic voltammetry, amperometry, and
      transmission electron microscopy.

PMID- 18330178
TI  - Solid lipid nanoparticles incorporating melatonin as new model for sustained oral
      and transdermal delivery systems.
AB  - melatonin (MT) is a hormone produced by the pineal gland at night, involved in
      the regulation of circadian rhythms. For clinical purposes, exogenous MT
      administration should mimic the typical nocturnal endogenous MT levels, but its
      pharmacokinetics is not favourable due to short half-life of elimination. Aim of
      this study is to examine pharmacokinetics of MT incorporated in solid lipid
      nanoparticles (SLN), administered by oral and transdermal route. SLN peculiarity
      consists in the possibility of acting as a reservoir, permitting a constant and
      prolonged release of the drugs included. In 7 healthy subjects SLN incorporating
      MT 3 mg (MT-SLN-O) were orally administered at 8.30 a.m. MT 3 mg in standard
      formulation (MT-S) was then administered to the same subjects after one week at
      8.30 a.m. as controls. In 10 healthy subjects SLN incorporating MT were
      administered transdermally (MT-SLN-TD) by the application of a patch at 8.30 a.m.
      for 24 hours. Compared to MT-S, Tmax after MT-SLN-O administration resulted
      delayed of about 20 minutes, while mean AUC and mean half life of elimination was
      significantly higher (respectively 169944.7 +/- 64954.4 pg/ml x hour vs. 85148.4
      +/- 50642.6 pg/ml x hour, p = 0.018 and 93.1 +/- 37.1 min vs. 48.2 +/- 8.9 min, p
      = 0.009). MT absorption and elimination after MT-SLN-TD demonstrated to be slow
      (mean half life of absorption: 5.3 +/- 1.3 hours; mean half life of elimination:
      24.6 +/- 12.0 hours), so MT plasma levels above 50 pg/ml were maintained for at
      least 24 hours. This study demonstrates a significant absorption of MT
      incorporated in SLN, with detectable plasma level achieved for several hours in
      particular after transdermal administration. As dosages and concentrations of
      drugs included in SLN can be varied, different plasma level profile could be
      obtained, so disclosing new possibilities for sustained delivery systems.

PMID- 18330179
TI  - Shape-dependent catalytic activity of CuO/MgO nanocatalysts.
AB  - CuO/MgO catalysts with various shapes have been obtained by using morphology
      controlled synthesis technology. It is demonstrated that there is a remarkable
      difference in catalytic activity for CO oxidation among these samples. However,
      when all these catalysts react with water before calcination, their shapes become
      irregular and similar, consequently, the difference of their catalytic activities
      disappears.

PMID- 18330180
TI  - Highly fluorescent dendrimers containing stilbene, and 4-styrylstilbene with
      resorcinarene cores: synthesis and optical properties.
AB  - Dendron conjugated branches of stilbene and 4-styrylstilbene groups have been
      attached to resor-cinarene cores. A noticeable effect in solution for all
      dendrimers was observed in the fluorescence quantum yield. The optical properties
      do not change with concentration in solution. The optical properties of thin
      films are identical to those of the solutions indicating the absence of
      intermolecular interactions. The dendrimers were characterized by 1H, 13C NMR,
      FTIR, UV-Vis, fluorescence spectroscopy, MALDI-TOF or FAB+ mass spectrometry, and
      elemental analysis.

PMID- 18330181
TI  - Electron beam modification of polymer nanospheres.
AB  - Polystyrene spheres, 500 nm in diameter, self-assembled on the surface of silicon
      oxide are modified by exposure to an electron beam in a scanning electron
      microscope. Under electron beam exposure at room temperature, the diameter of the
      polystyrene spheres decreases by approximately 13% following a 9.9 mC/cm2 dose.
      The shrinkage of the spheres offers a new route for nanosphere lithography where
      the gaps between the spheres can be accurately tuned. Exposure to electrons also
      alters the surface chemistry of the spheres, making the spheres much more
      resistant to oxygen plasma processing.

PMID- 18330182
TI  - Optical and magnetic properties of Ni-doped ZnO nanocones.
AB  - Ni-doped ZnO flower-like nanocones with wurzite structures were produced by
      oxidative evaporation of Zn and Ni powders. The Ni doping did not change the ZnO
      wurtzite structure. Raman scattering indicated that the normal lattice vibration
      modes are related to the hexagonal ZnO. Ni clusters and Ni oxides phases did not
      existed in the sample as characterized by XRD, XPS, and TEM. Upon excitations the
      nanocones could emit strong green light at 525 nm, which can be directly observed
      with a digital camera. The magnetic measurement indicated that the Ni-doped ZnO
      nanocone was high-Curie-temperature magnetic semiconductor.

PMID- 18330183
TI  - Synthesis and characterization of LnPO4 x nH2O (Ln = La, Ce, Gd, Tb, Dy) nanorods
      and nanowires.
AB  - Aqueous precipitation method has been used to synthesize lanthanide
      orthophosphates LnPO4 x nH2O (Ln = La, Ce, Gd, Tb, Dy) with high purity and
      yield. It has been shown by XRD, TGA, and FTIR characterization that the as
      synthesized samples are the LnPO4 hydrates (LnPO4 x nH2O) with hexagonal
      rhabdophane-type structure. The X-ray diffraction peaks and absorption of PO4(3-)
      groups show a systematic shift from LaPO4 x nH2O to DyPO4 x nH2O due to the
      effect of lanthanide ionic contraction. The value of n in LnPO4 x nH2O depends on
      the lanthanide element and synthetic condition. Field-emission scanning electron
      microscopy observations show the morphology of as-synthesized samples, which
      consist entirely of nanorods/nanowires with diameters of 30-100 nm and lengths
      ranging from several hundreds of nanometers to several micrometers. The
      anisotropic growth of crystals should be responsible for the formation of
      nanorods/nanowires, which is related to the hexagonal crystal structure.

PMID- 18330184
TI  - Y0.9 Er0.1 Al3(BO3)4 thin films prepared by the polymeric precursor method for
      integrated optics.
AB  - This work reports on the optimization of Yo.9 Er0.1 Al3(BO3)4 thin films for
      integrated optics. The films were deposited on silica and silicon substrates
      using the spin-coating technique involving solutions previously prepared by the
      polymeric precursor method. These deposits, 400-800 nm thick, were prepared by a
      5-10 multi-layer process and heat treatments at different temperatures from glass
      transition to crystallization temperature, using heating rates of 2 or 5 degrees
      C/min. The structural characterizations were performed using grazing incidence X
      ray diffraction and Fourier transform infrared spectroscopy (FT-IR). Water and/or
      hydroxyl contents were also evaluated from FT-IR spectra. Microstructural
      evolution in term of annealing temperatures was analyzed by high resolution
      scanning electronic microscopy and atomic force microscopy. Optical transmission
      spectra were used to determine the refractive index and thickness through the
      envelope method of the films. Finally, the film guiding and optical properties
      were studied by m-line spectroscopy. The best film showed a good waveguiding with
      high light-coupling efficiency close to the theoretical limit.

PMID- 18330185
TI  - Effect of deposition pressure on the morphology and structural properties of
      carbon nanotubes synthesized by hot-filament chemical vapor deposition.
AB  - Hot-filament chemical vapor deposition has developed into an attractive method
      for the synthesis of various carbon nanostructures, including carbon nanotubes.
      This is primarily due to its versatility, low cost, repeatability, up
      scalability, and ease of production. The resulting nano-material synthesized by
      this technique is dependent on the deposition conditions which can be easily
      controlled. In this paper we report on the effect of the deposition pressure on
      the structural properties and morphology of carbon nanotubes synthesized by hot
      filament chemical vapor deposition, using Raman spectroscopy and high-resolution
      scanning electron microscopy, respectively. A 10 nm-thick Ni layer, deposited on
      a SiO2/Si substrate, was used as catalyst for carbon nanotube growth. Multi
      walled carbon nanotubes with diameters ranging from 20-100 nm were synthesized at
      500 degrees C with high structural perfection at deposition pressures between 150
      and 200 Torr. Raman spectroscopy measurements confirm that the carbon nanotube
      deposit is homogeneous across the entire substrate area.

PMID- 18330186
TI  - Peroxidase catalytic cycle of MCM-41-entrapped microperoxidase-11 as a mechanism
      for phenol oxidation.
AB  - The encapsulation of microperoxidases (MPs) into molecular sieves with controlled
      pore size, such as the mesoporous silica MCM-41, represents a nanotechnology
      strategy to control the catalytic properties of MPs and mimic the enzymatic
      activity of hemoproteins. In this work, the ferric microperoxidase-11 (MP-11),
      obtained from trypsin-catalyzed hydrolysis of horse-heart cytochrome c, was
      entrapped in MCM-41, thus resulting in a catalyst (Fe(III)MP11MCM41) with
      catalase and monooxygenase properties. The entrapment of MP-11 inside MCM-41 was
      confirmed by elemental analysis and UV-visible spectrum, with a red shift in the
      Soret band indicating that the heme group was in a hydrophobic microenvironment.
      Similarly to catalase, the catalyst Fe(III)MP11MCM41 exhibited specificity for
      hydrogen peroxide to be converted to a high-valence oxidized intermediate,
      Compound II. Also mimicking catalase, the cleavage of hydrogen peroxide by
      MP11MCM41 resulted in O2 production detected by a Clark electrode. Phenol was
      able to act as reducing agent of MP11MCM41 Compound II leading to the completion
      of a peroxidase cycle, as confirmed by UV-visible spectrometry and EPR
      measurements. The analysis of the reaction products by high performance liquid
      chromatogram coupled to tandem mass spectrometry (HPLC/MS) revealed 2,4
      dihydroxyphenol as the product of phenol oxidation by MP11MCM41. Therefore, in
      addition to catalase activity, the catalyst MP11MCM41 also displayed
      monooxygenase properties, which was possible because the MP-11 heme iron promotes
      homolytic cleavage of the hydrogen peroxide generating hydroxyl radicals. With
      such characteristics, MCM-41-entrapped MP-11 is a promising catalyst for
      nanobiotechnological devices.

PMID- 18330187
TI  - Orthogonally-oriented nanotube arrays: experiment I.
AB  - Recently a new type of self-assembling surface has been proposed that, in theory,
      possesses a number of desirable tribological, electrical, and thermal
      characterstics. The surface consists of arrays of carbon nanotubes partially
      embedded lengthwise in a substrate such that when two arrayed surfaces are
      brought together orthogonally, the areal contact between them is small, limited
      to a lattice of nearly point-like contacts. These orthogonally-oriented nanotube
      arrays (ONAs) are predicted to exhibit: (i) surface adhesion (stiction) 10-100
      times less than for Teflon or other advanced perfluorocarbons; (ii) frictional
      coefficients up to 1000 times less than for conventional solids; (iii) ultra-low
      wear; and (iv) superior thermal and electrical conductivity. In this paper,
      laboratory methods are described for embedding nanotubes in trenched substrates.
      Using microscopically trenched substrates and a custom ultrasonic atomization
      source, experiments show that individual nanotubes can spontaneously and
      controllably entrench themselves via interfacial forces (capillary and surface
      tension). Results indicate ONAs might be relatively simply and inexpensively
      fabricated. More decisive experiments are proposed.

PMID- 18330188
TI  - Nanoengineering of surface modified silica particles to form core-shell and
      hollow nanospheres of iron oxide.
AB  - The method of synthesizing nanoshell of alpha-Fe2O3 on silica core nanoparticle
      and hollow alpha-Fe2O3 nanoparticles is described. The silica particles of
      approximately 160 nm diameter were surface modified using 3
      aminopropyltrimethoxysilane (APS) for easy adsorption of iron on it. These
      particles were treated with FeCl3 and further heat treated up to 1000 degrees C
      to get alpha-Fe2O3 shell of thickness approximately 20 nm. The hollow iron oxide
      particles were prepared using sacrificial core removal using dilute HF solution.
      The particles were characterized for their structure, morphology, bonding and
      surface chemistry using Transmission Electron Microscopy (TEM), X-ray Diffraction
      (XRD), Fourier Transform Infra Red Spectroscopy (FTIR), and X-ray Photoelectron
      Spectroscopy (XPS).

PMID- 18330189
TI  - Multicolor luminescence from transition metal ion (Mn2+ and Cu2+) doped ZnS
      nanoparticles.
AB  - Mn and Cu doped ZnS nanoparticles in powder form were prepared by a simple
      solvothermal route. Particle size and crystal structure of the products were
      investigated through X-ray diffraction study revealing the formation of cubic ZnS
      nanoparticles of average diameter 2.5 nm. Particle size was also verified by the
      high resolution transmission electron microscopic images. Blue emission at
      approximately 445 nm was observed from the undoped sample, which was attributed
      to the presence of large surface defects. With increasing doping concentration
      the defect related emission gradually quenches and subsequently the impurity
      related emissions appeared. Mn doped samples exhibited orange emission at
      approximately 580 nm which may be attributed to the transition between (4)T1 and
      (6)A1 energy levels of the Mn2+ 3d states. Whereas, the Cu doped ZnS
      nanoparticles exhibited a red shifted strong blue emission at approximately 466
      nm which is attributed to the transition of the electrons from the surface states
      to the 't2' levels of Cu impurities.

PMID- 18330190
TI  - Optimization of the synthesis of alpha-MoO3 nanoribbons and hydrodesulfurization
      (HDS) catalyst test.
AB  - An optimized process for synthesis of alpha-MoO3 nanoribbons characterized by
      uniform morphology and composition was carried out. The optimized process turned
      out to be the aging of a precursor of an aqueous solution of ammonium
      heptamolybdate for a week under constant stirring at 333 K; followed by
      hydrothermal treatment for 36 h up to 48 h at 473 K. The dimensions of the
      nanoribbons were between 5 and 10 microm in length and a width between 100 and
      600 nm. The thickness was between 60 and 200 nm. This material was tested for
      hydrodesulfurization (HDS) of dibenzothiophene (DBT) by in situ activation and
      showed its catalytic activities to be similar to those of unsupported MoS2
      catalysts. The structure and morphology of these materials was characterized by
      analytical transmission electron microscopy, scanning electron microscopy, and X
      ray diffraction using the Rietveld method to determine the quantitative
      crystallographic phases. A chemical semiquantitative analysis was carried out by
      energy dispersive spectroscopy and a qualitative analysis was carried out by
      electron energy loss spectroscopy.

PMID- 18330191
TI  - Conductivity relaxation in lodomolybdate glass-nanocomposites embedded with znO
      nanoparticles and alpha-AgI nanocrystals.
AB  - We have reported the conductivity relaxation of the 0.70AgI-0.15Ag20-0.15(xZnO-(1
      x)MoO3), glass-nanocomposites embedded with ZnO nanoparticles and alpha-Agl
      nanocrystals. Formation of ZnO nanoparticles and alpha-AgI nanocrystals was
      confirmed from field emission scanning electron microscopy (FE-SEM) and high
      resolution transmission electron microscopy (HR-TEM). It is observed that the
      conductivity relaxation process depends upon the size of the ZnO nanoparticles
      embedded in the host glass matrix. The variation of conductivity relaxation time
      and stretched exponent is correlated with their structure. The scaling of the
      modulus spectra reveals that the relaxation dynamics of Ag+ ions is independent
      of temperature but depends on composition.

PMID- 18330192
TI  - The transformative dental experience.

PMID- 18330193
TI  - Restorative dentistry: current developments and a look to the future.

PMID- 18330194
TI  - Utilizing a restorative approach to correct an adult skeletal class III
      malocclusion.
AB  - When determining if treatment for malocclusion is indicated, the clinician must
      understand how the malocclusion affects the patient aesthetically, functionally,
      and biologically, as well as any impact of treatment. It is important to consult
      the patient and advise when a less invasive orthodontic treatment plan may be
      optimal. Once the patient is fully informed of the treatment options and desires
      treatment without orthodontics, a restorative/ prosthodontic approach using
      veneers, crowns, or fixed prosthetics can provide exceptional strength, function,
      and aesthetics. As in all cases, thorough evaluation and planning are essential.
      The decision to proceed with restorative alignment of the teeth rather than
      orthodontic alignment is dependent on full disclosure to the patient and the
      clinician's understanding of preparation design, aesthetics, and occlusion. As
      demonstrated in this class III case, with proper examination, diagnosis,
      treatment planning, and communication, excellent aesthetic, phonetic, and
      functional results can be achieved and maintained. As with all full-mouth
      restorative cases, periodic occlusal evaluation will be necessary at normal
      hygiene intervals.

PMID- 18330195
TI  - Developmental mandibular salivary gland defect: the importance of clinical
      evaluation.

PMID- 18330196
TI  - Oral surgery simplified with radiosurgery.

PMID- 18330197
TI  - Fluoride...it's still good.

PMID- 18330198
TI  - Improving shade communication.

PMID- 18330199
TI  - Benefits of fiber posts: clinical application of a new post system.

PMID- 18330200
TI  - Solution for the challenging implant.

PMID- 18330201
TI  - Digital occlusal splints.
AB  - A new digital process for producing occlusal splints is described. The process
      mirrors conventional restorative CAD/CAM systems consisting of scanning,
      customized CAD design, and machining. The method provides precise and consistent
      digital control over articulation and design parameters, and is suitable for
      mounted and unmounted cases. With over 2,500 beta cases to date, an overall
      reduction in adjustment time has been generally reported.

PMID- 18330202
TI  - Soft-tissue surgery: use of the Er,Cr:YSGG laser.

PMID- 18330203
TI  - Replacement of maxillary central incisors with implants.

PMID- 18330204
TI  - New attach ment procedure: using the pulsed Nd:YAG laser.

PMID- 18330205
TI  - Technologies for a new office or upgrading a current office.

PMID- 18330206
TI  - Avoiding claim delays and denials.

PMID- 18330207
TI  - Culture of giving. a first step toward greatness.

PMID- 18330208
TI  - Electrical interference of pacemaker activity by electrical dental devices: a
      short review.

PMID- 18330209
TI  - Crown lengthening surgery--the relevance of biological width.

PMID- 18330210
TI  - Combined periodontal and pulpal disease--a diagnostic minefield.

PMID- 18330212
TI  - Investigating the dopaminergic synapse in vivo. I. Molecular imaging studies in
      humans.
AB  - Dopaminergic synaptic function may be assessed either at the presynaptic terminal
      or at the postsynaptic binding sites using molecular in vivo imaging methods.
      Apart from the density of binding sites, parameters such as alterations in
      dopamine synthesis, dopamine storage or dopamine release can be quantified either
      by application of specific radiotracers or by assessing the competition between
      the exogenous radioligand and endogenous dopamine. Investigations of humans in
      both clinical and experimental settings have yielded evidence that disturbances
      of dopaminergic function may be associated with numerous neurological and
      psychiatric conditions, among which are movement disorders, schizophrenia,
      attention-deficit hyperactivity disorder, depression and drug abuse. This article
      gives an overview of those studies, which so far have been performed on
      dopaminergic neurotransmission in humans using in vivo imaging methods. We focus
      on disease-related deficiencies within the functional entity of the dopaminergic
      synapse. Taken together, in vivo findings yield evidence of presynaptic
      dysfunctions in Parkinson's disease with decreases in striatal dopamine
      synthesis, dopamine storage, dopamine release and dopamine transporter binding.
      In contrast, 'Parkinson plus' syndromes (multiple system atrophy, progressive
      supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies) are
      characterized by both pre- and postsynaptic deficiencies with reductions in
      striatal dopamine synthesis, dopamine storage, dopamine release, and dopamine
      transporter, as well as D, and D, receptor binding. In patients with Huntington's
      disease, postsynaptic dysfunctions with reductions of striatal D1 and D2 receptor
      binding have become apparent, whereas attention-deficit/ hyperactivity disorder
      is mainly characterized by presynaptic deficits with increases in dopamine
      transporter binding. Interestingly, findings are also consistent with respect to
      drug abuse: cocaine, amphetamine, methylphenidate, heroin, alcohol and nicotine
      invariably act via enhancement of dopamine release in dorsal and/ or ventral
      striatal regions. In vivo findings additionally suggest that not only D2 receptor
      binding but also the extent of dopamine release is lower in individuals with a
      history of drug abuse. Findings become inconsistent with increasing complexities
      of psychiatric conditions. As yet, there is no clear evidence as to the
      contributions of the individual presynaptic and postsynaptic constituents of the
      dopaminergic synapse to the pathophysiologies of schizophrenia and depression. As
      these diseases can be conceived as the result of a variety of dysfunctions and
      dysregulations within an intricate network of neurotransmitter systems, regional
      investigations of one single pre- or postsynaptic constituent may not reach far
      enough to disentagle the interrelationships between the constituents of one let
      alone a variety of neurotransmitter systems.

PMID- 18330211
TI  - Circuits formultisensory integration and attentional modulation through the
      prefrontal cortex and the thalamic reticular nucleus in primates.
AB  - Converging evidence from anatomic and physiological studies suggests that the
      interaction of high-order association cortices with the thalamus is necessary to
      focus attention on a task in a complex environment with multiple distractions.
      Interposed between the thalamus and cortex, the inhibitory thalamic reticular
      nucleus intercepts and regulates communication between the two structures. Recent
      findings demonstrate that a unique circuitry links the prefrontal cortex with the
      reticular nucleus and may underlie the process of selective attention to enhance
      salient stimuli and suppress irrelevant stimuli in behavior. Unlike other
      cortices, some prefrontal areas issue widespread projections to the reticular
      nucleus, extending beyond the frontal sector to the sensory sectors of the
      nucleus, and may influence the flow of sensory information from the thalamus to
      the cortex. Unlike other thalamic nuclei, the mediodorsal nucleus, which is the
      principal thalamic nucleus for the prefrontal cortex, has similarly widespread
      connections with the reticular nucleus. Unlike sensory association cortices, some
      terminations from prefrontal areas to the reticular nucleus are large, suggesting
      efficient transfer of information. We propose a model showing that the
      specialized features of prefrontal pathways in the reticular nucleus may allow
      selection of relevant information and override distractors, in processes that are
      deranged in schizophrenia.

PMID- 18330213
TI  - Investigating the dopaminergic synapse in vivo. II. Molecular imaging studies in
      small laboratory animals.
AB  - Dopaminergic synaptic function may be assessed either at the presynaptic terminal
      or at the postsynaptic binding sites using molecular in vivo imaging methods.
      Apart from the density of binding sites, parameters such as alterations in
      dopamine synthesis, dopamine storage or dopamine release can be quantified either
      by application of specific radiotracers or by assessing the competition between
      the exogenous radioligand and endogenous dopamine. The performance of animal
      studies allows the induction of specific short-term or long-term synaptic
      conditions via pharmacological challenges or infliction of neurotoxic lesions.
      Therefore, small laboratory animals such as rats and mice have become invaluable
      models for a variety of human disorders. This article gives an overview of those
      small animal studies which have been performed so far on dopaminergic
      neurotransmission using in vivo imaging methods, with a special focus on the
      relevance of findings within the functional entity of the dopaminergic synapse.
      Taken together, in vivo investigations on animal models of Parkinson's disease
      showed decreases of dopamine storage, dopamine release and dopamine transporter
      binding, no alterations of dopamine synthesis and DA release, and either
      increases or no alterations of D2 receptor binding, while in vivo investigations
      of animal models of Huntington's disease. showed decreases of DAT and D1 receptor
      binding. For D2 receptor binding, both decreases and increases have been
      reported, dependent on the radioligand employed. Substances of abuse, such as
      alcohol, amphetamine and methylphenidate, led to an increase of dopamine release
      in striatal regions. This held for the acute application of substances to both
      healthy animals and animal models of drug abuse. Findings also showed that
      chronic application of cocaine induced long-term reductions of both D1 and D2
      receptor binding, which disappeared after several weeks of withdrawal. Finally,
      preliminary results yielded the first evidence that acute pplication of
      haloperidol might induce a reduction of dopamine transporter binding, indicating
      an enhancement of dopamine release into the synaptic cleft. It is remarkable to
      what degree the findings obtained with small animal imaging devices correspond to
      the results of clinical and experimental studies on humans. This agreement
      underlines the validity of small animal imaging methods and demonstrates the
      feasibility of further investigations on animal models of human diseases.

PMID- 18330214
TI  - Speech error elicitation and co-occurrence restrictions in two Ethiopian Semitic
      languages.
AB  - This article reports the results of speech error elicitation experiments
      investigating the role of two consonant co-occurrence restrictions in the
      productive grammar of speakers of two Ethiopian Semitic languages, Amharic and
      Chaha. Higher error rates were found with consonant combinations that violated co
      occurrence constraints than with those that had only a high degree of shared
      phonological similarity or low frequency of co-occurrence. Sequences that
      violated two constraints had the highest error rates. The results indicate that
      violations of consonant co-occurrence restrictions significantly increase error
      rates in the productions of native speakers, thereby supporting the psychological
      reality of the constraints.

PMID- 18330215
TI  - Orthographic representations in spoken word priming: no early automatic
      activation.
AB  - The current study investigated the modulation by orthographic knowledge of the
      final overlap phonological priming effect, contrasting spoken prime-target pairs
      with congruent spellings (e.g., 'carreau-bourreau', /karo/-/buro/) to pairs with
      incongruent spellings (e.g., 'zero-bourreau', /zero/-/buro/). Using materials and
      designs aimed at reducing the impact of response biases or strategies, no
      orthographic congruency effect was found in shadowing, a speech recognition task
      that can be performed prelexically. In lexical decision, an orthographic effect
      occurred only when the processing environment reduced the prominence of
      phonological overlap and thus induced participants to rely on word spelling.
      Overall, the data do not support the assumption of early, automatic activation of
      orthographic representations during spoken word recognition.

PMID- 18330216
TI  - Rhythm versus analogy: prosodic form variation in Dutch compounds.
AB  - Creating compound nouns is the most productive process of Dutch morphology, with
      an interesting pattern of form variation. For instance, staat 'nation' simply
      combines with kunde 'art' (staatkunde 'political science, statesmanship'), but
      needs a linking element s or en to form staatsschuld 'national debt' and
      statenbond 'confederation'. Previous research has shown that the use of linking
      elements is guided by paradigmatic analogy, a factor that in the absence of other
      factors would lead to paradigm uniformity. However, there is considerable freedom
      in the use of linking elements, suggesting that other factors are relevant as
      well. We present studies showing that both stress and length affect their use,
      and that, in an experimental setting, the linking element en is less favored in
      lengthened compounds. However, the results observed in this experiment can only
      be explained satisfactorily in terms of rhythm: the preference for a recurrent
      pattern of stressed and unstressed syllables. The general conclusion of this
      study concerns the distinction between language behavior guided by stored
      knowledge or by processing factors. Models based on analogy (exemplar-based
      models) rely on stored knowledge. This study shows that apart from that, rhythm
      plays its own role. Rhythmic structures facilitate language processing, and a
      preference for perfect rhythm explains which variant of a compound (with or
      without the linking element) is chosen. Given the universal nature of analogy and
      rhythm, the issue of the balance between these two components of linguistic
      knowledge is relevant for a wide array of languages.

PMID- 18330217
TI  - The analysis of low accentuation in Estonian.
AB  - In Estonian, as in a number of other languages, the nuclear pitch accent is often
      low and level. This paper presents two studies of this phenomenon. The first, a
      phonetic analysis of carefully structured read sentences shows that low
      accentuation can also spread to the prenuclear accents in an intonational phrase.
      The resulting sentence contours are used as evidence to evaluate alternative
      phonological analyses of low accentuation, and H + L* is shown to account best
      for the data. The second study presents quantitative evidence from fundamental
      frequency values which supports this phonological analysis. Finally, the
      distribution of prenuclear pitch accents is discussed. High and low accents can
      co-occur in an intonational phrase, but only in patterns obeying a specific
      sequential constraint. A fragment of an intonational grammar for Estonian is
      presented capturing the observed distributional restrictions.

PMID- 18330218
TI  - Change--more than just the climate.

PMID- 18330219
TI  - Retooling the ethanol industry: thermophilic anaerobic digestion of thin stillage
      for methane production and pollution prevention.
AB  - Anaerobic digestion of corn ethanol thin stillage was tested at thermophilic
      temperature (55 degrees C) with two completely stirred tank reactors. The thin
      stillage wastestream was organically concentrated with 100 g/L total chemical
      oxygen demand and 60 g/L volatiles solids and a low pH of approximately 4.0.
      Steady-state was achieved at 30-, 20-, and 15-day hydraulic retention times
      (HRTs) and digester failure at a 12-day HRT. Significant reduction of volatile
      solids was achieved, with a maximum reduction (89.8%) at the 20-day HRT. Methane
      yield ranged from 0.6 to 0.7 L methane/g volatile solids removed during steady
      state operation. Effluent volatile fatty acids below 200 mg/L as acetic acid were
      achieved at 20- and 30-day HRTs. Ultrasonic pretreatment was used for one
      digester, although no significant improvement was observed. Ethanol plant natural
      gas consumption could be reduced 43 to 59% with the methane produced, while
      saving an estimated $7 to $17 million ($10 million likely) for a facility
      producing 360 million L ethanol/y.

PMID- 18330220
TI  - Simultaneous nitrification and denitrification of municipal wastewater in aerobic
      membrane bioreactors.
AB  - Simultaneous nitrification-denitrification (SND) of municipal wastewater was
      investigated in a laboratory-scale membrane bioreactor (MBR) operated at two
      different hydraulic retention times (HRTs), 0.5 and 1 day, dissolved oxygen 3.0
      to 0.5 mg/L, and solids retention time (SRT) between 28 and 120 days. The organic
      loading rate (OLR) (0.11 to 0.64 kg chemical oxygen demand [COD]/m3/d) and
      influent soluble COD (SCOD)/ total Kjeldahl nitrogen (TKN) ratio (5 to 19) were
      varied by the addition of glucose. The ammonia-nitrogen and TKN removals were
      over 97%, and total nitrogen removal was approximately 89% in the MBR. The
      maximum specific nitrification rates (98 mg N/d/g VSS) and specific
      denitrification rates (81 mg N/d/g VSS) occurred at an SCOD/TKN ratio of 9.1. The
      optimum conditions for maximum total nitrogen removal by SND in a single reactor
      MBR have been found to be low dissolved oxygen (< 0.6 mg/L) and high OLR
      (approximately 0.64 kg COD/m3/d) at an HRT of 0.5 day and SRT of approximately 85
      days.

PMID- 18330221
TI  - Modeling the formation and fate of odorous substances in collection systems.
AB  - A conceptual model that simulates the formation and fate of odorous substances in
      branched collection systems is presented. The model predicts the activity of the
      relevant biomass phenotypes under aerobic, anoxic, and anaerobic conditions in
      force mains and gravity sewers. The formation and fate of individual, malodorous
      substances in the bulk water, biofilms, and sediments are modeled. The release of
      odorous compounds from the bulk water to the sewer gas phase, their fate in the
      gas phase, and their subsequent release into the urban atmosphere is simulated.
      Examples of model application include the prediction of hydrogen sulfide and
      malodorous fermentation products from force mains and gravity sewers.

PMID- 18330222
TI  - Role of protein, amino acids, and enzyme activity on odor production from
      anaerobically digested and dewatered biosolids.
AB  - The main objective of this research was to test the hypothesis that bioavailable
      protein and, more specifically, the sulfur-containing amino acids within the
      protein, can be degraded by proteolytic enzymes to produce odor-causing compounds
      -mainly volatile sulfur compounds (VSCs)--during biosolids storage. To achieve
      these objectives, samples of digester effluent and cake solids were collected at
      11 different wastewater treatment plants in North America, and the samples were
      analyzed for protein and amino acid content and general protein-degrading enzyme
      activity. At the same time, cake samples were stored using headspace bottles, the
      concentration of VSCs were measured using gas chromatography, and olfactometry
      measurements were made by a trained odor panel. The results showed that the bound
      cake protein content and methionine content was well-correlated with VSC
      production and the detection threshold measured by the odor panel.

PMID- 18330223
TI  - Catalytic oxidative treatment of diluted black liquor at mild conditions using
      copper oxide/cerium oxide catalyst.
AB  - Wet-air oxidation of diluted black liquor (chemical oxygen demand [COD]
      approximately 3250 to 14 500 mg/L) was performed at mild operating conditions
      (temperature = 388 to 423 K and total pressure = 0.6 MPa) in the presence of
      heterogeneous 60% copper oxide (CuO)/ 40% cerium oxide (CeO2) catalyst. Maximum
      COD reduction of 77.3% was obtained at 423 K at pH 3.0, which was marginally
      higher than that obtained at 413 K temperature (77.1%). In the acidic environment
      (pH < or = 3), most of the COD was removed in the form of settleable solids
      during the transient heating of the wastewater from room temperature to the
      desired one. The solid residue obtained after the reaction has a heating value of
      20.1 MJ/kg, which is comparable with that of Indian coal. Thermal degradation
      kinetic determination suggested that thermal characteristics of the solid residue
      are well represented by a power law model with Agarwal and Sivasubramanian
      approximation (Safi et al., 2004).

PMID- 18330224
TI  - Performance of wastewater subsurface drip emitters at low and normal pressure.
AB  - Subsurface drip distribution is an important on-site wastewater treatment
      technique widely used with various soil types and restricted site conditions.
      This study evaluated the performance of five subsurface wastewater drip products
      under eight pressures, ranging from 0 to 310 kPa. Results showed that Netafim
      Bioline pressure-compensating emitters (Netafim Irrigation Inc., Fresno,
      California) had an application uniformity coefficient of 95% and a coefficient of
      variance (C(v)) of 4.9%. The average uniformity coefficient of Geoflow Wasteflow
      products (Geoflow USA, Charlotte, North Carolina) was 94.4%, with a C(v) value of
      6.8%. Flowrate and pressure relationships were developed by analyzing low and
      normal operational pressure ranges, and R-square values ranged from 1.000 to
      0.301. Geoflow pressure-compensating products were non-pressure-compensating
      emitters under low pressure. Netafim pressure-compensating emitters were
      partially pressure-compensating under low pressures. In normal operational
      pressure ranges, both Geoflow and Netafim products were fully pressure
      compensating. Netafim pressure-compensating products were characterized as
      pressure-compensating over the full range of operational pressures.

PMID- 18330225
TI  - Geochemical and geostatistical investigations of chromium pollution in
      groundwater.
AB  - Geochemical and geostatistical study of the chromium concentration in groundwater
      occurring at variable depths of 12 to 33.5 m (40 to 110 ft) in the Karachi urban
      area of Pakistan have been made. Samples were collected at variable distances,
      with a maximum of 1 km interval, on the bases of population, industries, types,
      and density. The chromium concentration has also been worked out to deduce the
      threshold value of the area under study and the estimation of probability impact
      modeling, in terms of concentration variation, by using the disjunctive kriging
      technique. The outcome of the present work appears to be a good tool to decipher
      pollution variation in the groundwater of highly urbanized areas, with respect to
      the population and industries. The patterns of distribution of chromium
      concentration in groundwater and pollution hotspots in particular localities
      appear to be more related to the types of industries than to the effect of
      population types.

PMID- 18330226
TI  - Effect of heavy metals on earthworm activities during vermicomposting of
      municipal solid waste.
AB  - The effect of heavy metals on the activities of earthworm species Eudrillus
      eugineae was studied during vermicomposting of municipal solid waste (MSW) spiked
      with heavy metals. The activities of earthworms, in terms of growth and biomass
      production and number of cocoons produced, were monitored periodically, and the
      concentration of heavy metals in earthworms and substrates was determined at
      definite intervals. Laboratory-scale experiments were performed by mixing
      individual heavy metals in MSW. Copper, cadmium, chromium, lead, and zinc were
      selected for the study. The study concludes that heavy metals tend to accumulate
      in the body of earthworms; hence, the inherent concentration of heavy metals in
      the substrate before vermicomposting must be considered in view of composting of
      MSW and its application to soil. It was observed that copper and cadmium were
      toxic for the worms at 1.5 and 0.1 g/kg of the waste, respectively. The studies
      also suggest that earthworms are susceptible to the free form of heavy metals.
      Cadmium is the most toxic metal, followed by copper. Based on the investigation
      and observation, it was also found that earthworms should be separated from
      castings before the use of castings in soil amendments.

PMID- 18330227
TI  - A load model based on antecedent dry periods for pollutants in stormwater.
AB  - A load model for stormwater constituents is proposed that describes mass retained
      on the drainage area after previous storms, as a function of a weighted sum of
      previous antecedent dry periods. It was used to compute the event load for 14
      constituents--zinc, copper, cadmium, nickel, chromium, lead, mercury, silver,
      total suspended solids (TSS), E. coli, fecal coliform, total soluble phosphorus,
      total phosphorus, and 5-day biochemical oxygen demand. The results show
      acceptable fits for most constituents based on over 400 rain events (2000 to
      2004) in Milwaukee, Wisconsin. Considering the retained pollutant mass after one
      previous storm rather than assuming the area to be clean after the previous storm
      gives more accurate results for all constituents, except TSS and silver. The
      model can be used for mixed land-use areas. The ratios of deposition fluxes of
      zinc and individual metals were determined at a major parking lot producing a
      profile characteristic of automobile emissions.

PMID- 18330228
TI  - Water quality performance of a batch-type stormwater detention basin.
AB  - The objective of this research was to modify an extended detention basin to
      provide batch treatment of stormwater runoff. An automated valve/controller was
      developed and placed on the outlet of a detention basin in Austin, Texas, which
      allowed the water quality volume to be retained in the basin for a preset length
      of time. The influent and effluent of the modified basin were monitored for total
      suspended solids (TSS), nutrients, chemical oxygen demand (COD), and total and
      dissolved metals. Statistically significant removal of total metals, COD, total
      nitrogen, total phosphorus, and TSS was observed, with a discharge event mean TSS
      concentration of 7 mg/L and a TSS removal efficiency of 91%. The modified basin
      has substantially better pollutant removal than conventional extended detention
      basins and is comparable with that of Austin sand filters, which are a common
      structural stormwater treatment system in the Austin area. The valve also can be
      used to isolate hazardous material spills.

PMID- 18330229
TI  - Investigation and modeling of solar UV-induced chlorine decay in disinfection
      contact basins at full-scale wastewater treatment plants.
AB  - Residual chlorine loss due to UV sunlight in the chlorine disinfection contact
      basins (DCBs) was investigated at two full-scale wastewater treatment plants
      (WWTPs). Chlorine decay due to solar UV-induced photochemical reaction was found
      to be significant and had diurnal and seasonal variations. The total chlorine
      loss due to sunlight ranged from 19 to 26% of the total chlorine chemical use at
      the two plants studied. Covering chlorine contact basins led to more stable
      chlorine demand regardless of the diurnal and seasonal sunlight intensity.
      Therefore, covering chlorine contact basins offers more stable, or accurate,
      chlorine dosage and effluent residual control and requires less effort by plant
      operators. A mathematical model was developed to calculate the amount of UV
      induced chlorine decay. The model developed can be used to estimate the UV
      induced chlorine decay rate and total chlorine loss due to sunlight at WWTPs with
      various basin configurations, flowrates, chlorine dosages, and geographical
      locations. The model results allow the capital cost of covering needs to be
      assessed against the chlorine chemical cost savings.

PMID- 18330230
TI  - Oxidation of industrial dyeing wastewater by supercritical water oxidation in
      transpiring-wall reactor.
AB  - Industrial dyeing wastewater was oxidized in supercritical water in a transpiring
      wall reactor, using hydrogen peroxide as an oxidant. Experiments were performed
      at 595 to 704 K and 18 to 30 MPa, with an oxidant dosage ratio ranging from 0.6
      to 2.0. A chemical oxygen demand (COD) removal of more than 98.4% was achieved at
      704 K and 28 MPa, with a retention time less than 35 seconds, which increased
      with the temperature, pressure, and oxidant. A modified first-order rate
      expression was regressed from experimental data, taking into account the
      influence of induction time. The resulting pre-exponential factor, A, and
      activation energy, Ea, were 1.07 seconds(-1) and 12.12 kJ x mol(-1),
      respectively, while the reaction order for feed wastewater (based on COD) and
      oxidant were assumed to be 1 and 0, respectively. Gas chromatography/mass
      spectrometry analysis for effluents indicated that carbon dioxide, carbon
      monoxide, and nitrogen were the main reaction products, and phenol;
      benzenecarboxylic acid; 1, 2-benzenedicarboxylic acid; and isoquinoline were
      detected as intermediates.

PMID- 18330231
TI  - [Review of current situations and prospects of research and development on
      traditional Chinese medicine cosmetics].
AB  - The definition, history, classification and advantages of traditional Chinese
      medicine cosmetics (TCMC) were summarized in this article. The domestic and
      foreign current situations of research and development of TCMC were particularly
      introduced. The application and authorization of TCMC in China were also briefly
      mentioned. Finally, the developmental prospects of TCMC in China were discussed
      in two aspects of the strategy of the R&D and the problems facing when it was
      marketed.

PMID- 18330232
TI  - [Advances in study of genus Curcuma].
AB  - The recent progress in the studies on chemical constituents, pharmacological
      activity and quality control of the medical plants of genus Curcuma were
      summarized. These plants contain various chemical constituents and have broad
      bioactivities such as anti-oxidation activity, anti-tumor and anti-inflammatory.
      It is complex when it is used for traditional Chinese medicine(TCM) because of
      its multispeciese and multiresources. The author believe that a deep research of
      the quality criterion about this genus can solve many problems of the further
      investigation and ensure the safety and utility of TCM.

PMID- 18330233
TI  - [Advances in studies on effect superiorities of traditional Chinese medicine on
      chronic hepatitis B].
AB  - Determination of treatment based in pathogenesis obtained through differentiation
      of symptoms and signs is the characteristic of traditional Chinese medicines'
      treatment on chronic hepatitis B. There are important effects and special
      superiorities for traditional Chinese medicines on resisting hepatic fibrosis,
      improving liver function, protecting liver cells and relieveing the symptoms. The
      therapeutic effects about the only traditional Chinese medicine and traditional
      Chinese medicine added western medicine compared with the only western medicine
      was reviewed in order to explain the traditional Chinese medicine' s therapeutic
      superiorities.

PMID- 18330234
TI  - [Study of roasted liquorice decoction on arrhythmia].
AB  - The treatment of roasted liquorice decoction on the disease cause and
      pathogenesis, pharmacology study and the clinical study were analyzed. roasted
      liquorice decoction can replenishing yin and supplementing blood, activating yang
      and returning pulse and its antiarrhythmic effect may involve in influencing
      action potential of myocardial, inhabiting platelet activate and protecting
      endothelial cells.

PMID- 18330235
TI  - [Effects of climate factors on quality of Chrysanthemum morifolium originated
      from Wenxian county].
AB  - OBJECTIVE: To study the effects of climate factors on the Chrysanthemum
      morifolium originated from Wenxian county (i. e "huaiju") for assuring the
      quality of medicinal C. morifolium. METHOD: The content of water-soluble
      extracts, protein, sugar, flavonoid and chlorogenic acid of "huaiju" collected
      from Henanwenxian, Jiangsunanjing and Zhejiangtongxiang were selected as the
      indicator and determined, climate data of the corresponding places were collected
      for studying the effects on "huaiju" quality through path analysis and
      correlation analysis. RESULT AND CONCLUSION: There existed no obviously
      differences among the detected indicators except the soluble sugar content.
      Sunlight, temperature and precipitation showed more effects on quality of
      "huaiju", the sunlight had the most direct effect on flavonoid, the 10 cm ground
      temperature had the most direct effect on chlorogenic acid.

PMID- 18330236
TI  - [Mechanism of effects of soil microbes on cuttings rooting of Huperzia serrata].
AB  - OBJECTIVE: To study the effects of soil microbes of habitats on the cuttings
      rooting of Huperzia serrata and its mechanism. METHOD: The cuttings of H. serrata
      were planted on the primary habitat soil and on the soil autoclaved, rooting
      rates were examined respectively. Changes of contents of phenolic compounds
      (catechin, quercetin, chlorogenic acid, ferulic acid) and indoleacetic acid (IAA)
      , and changes of activities of polyphenoloxidase (PPO) and peroxydase (POD)
      during the cuttings rooting were determined. RESULT: Soil microbes of primary
      habitat could increase the rooting rate and the number of roots, could increase
      contents of catechin, chlorogenic acid, ferulic acid and IAA during rooting, and
      could affect activities of PPO and POD. CONCLUSION: During the rooting higher
      contents of catechin, chlorogenic, ferulic acid and IAA caused by soil microbes
      of primary habitat are important factor for rooting rate.

PMID- 18330237
TI  - [Study on quantitative assessment of Siraitia grosvenorii germplasms by general
      index].
AB  - OBJECTIVE: To establish a weight-marking method and evaluate Siraitia grosvenorii
      germplasms. METHOD: The characters of 21 kinds of S. grosvenorii germplasms in
      the field and the lab were analyzed, seven important characters were selected to
      weight the marks. A general evaluation index was made and used to evaluate S.
      grosvenorii germplasms. RESULT: The evaluation result of 21 kinds of S.
      grosvenorii germplasms by the weight-marking method was consistent with
      production practice. Meanwhile, the new variety Yongqing No. 1 and major
      cultivars were the superior germplasms. CONCLUSION: A rational technique system
      of evaluating S. grosvenorii germplasms was established, and the superior
      germplasms were selected.

PMID- 18330238
TI  - [Analysis on biomasses and contents of active components in roots of Salvia
      miltiorrhiza from different populations].
AB  - OBJECTIVE: To provide some evidence for breeding excellent lines of Salvia
      miltiorrhiza. METHOD: Contents of tanshinone II(A), cryptotanshinone, salvialic
      acid A and salvianolic acid B in root of S. miltiorrhiza from different
      populations were determined by HPLC. Total tanshinone and total salvianolic acids
      were determined by spectrophotometry. RESULT: The biomass of individual plant
      from Zhongjiang of Sichuan province, content of tanshinone II(A), from Shanxi
      province, cryptotanshinone and total tanshinone from Zhongjiang of Sichuan
      province, salvialic acid A of High-Stem cultivation from Hebei province,
      salvianolic acid B and total salvianolic acids of tetroploid were higher than the
      other samples, respectively. With the value of biomass of individual plant
      multiplying contents of every active components as indicative constituents, the
      multiplying value from Zhongjiang of Sichuan province was higher than the other
      samples. CONCLUSION: With biomasses and effective components as indicative
      constituents, it suggested that S. miltiorrhiza from Zhongjiang of Sichuan
      province was a better derivative material.

PMID- 18330239
TI  - [Change of endogenous hormone around sprout tumble of Pinellia ternata under high
      temperature stress].
AB  - OBJECTIVE: To study the change of endogenous hormone (ABA, IAA, JA, GA3, ZR) in
      the leaves, petioles, tubers of Pinellia ternate around sprout tumble. It also
      provided some valuable information to prevent sprout tumble and increase
      production. METHOD: Tubers of P. ternata were cultured firstly at (23 +/- 1)
      degree C for certain days, and then they were coerced under (30 +/- 1 ) degree C
      stress in the same artificial climate boxes. The endogenous hormones in leaves,
      petioles and tubers during different stages of high temperature stress were
      determined with Enzyme-linked Immunosorbent Assays (ELISA). RESULT: After under
      high temperature stress, ABA content in leaves, petioles and tubers increased
      obviously. Similarly, JA content rose all in the leaves, petioles and tubers. But
      in the same conditions IAA content declined significantly in the leaves and
      petioles. In the tubers, IAA content also decreased, but not quickly. With the
      extension of high temperature coercion, the leaves, petioles, tubers, ZR content
      were gradually falling off. In the leaves of GA3 content rose markedly at the
      third day, fell down at the sixth day, but remained higher than before treatment.
      With the extension of the processing time, GA3 content fell off in the petioles
      and tubers. CONCLUSION: ABA, JA, ZT and GA3 played an important role in
      controlling sprout tumble of P. ternata.

PMID- 18330240
TI  - [Determination of HPLC fingerprint of Qingfengtong capsule].
AB  - OBJECTIVE: To establish a fingerprint analysis method of Qingfengtong capsule by
      HPLC. METHOD: The samples were extracted with 70% ethanol in an ultrasonic bath.
      The extracts were analyzed at 35 degrees C on a Diamonsil C18 column (4.6 mm x
      250 mm, 5 microm) with 0.1 mol x L(-1) potassium dihydrogen phosphate water
      solution as mobile phase A, and methanol as mobile phase B. The analysis followed
      a linear gradient elution program. Initial condition of the mobile phase was 10%
      B for 2 minutes; then changed to 90% B in 40 minutes. The flow rate was kept at
      1.0 ml x min(-1) and the detector wavelength was 262 nm. RESULT: The main peaks
      in fingerprint chromatogram of Qingfengtong capsules were separated fairly well.
      The results of method validation meet the requirements for the fingerprints.
      CONCLUSION: The established method can be used for the quality control of
      Qingfengtong capsules.

PMID- 18330241
TI  - [Determination of iridoids and triterpenes in herb of Swertia pseudochinesis by
      RP-HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for the determination of swertiamarin,
      sweroside, gentiopicrin and oleanolic acid in different parts of Swertia
      pseudochinesis. METHOD: A Zorbax SB-C18 (4.6 mm x 250 mm, 5 microm) column was
      used with acetonitrile-water (10:90) and methnol-water(86:14) at detection
      wavelengths of 238 nm, 246 nm, 274 nm and 207 nm for swertiamarin, sweroside,
      gentiopicrin and oleanolic acid respectively. The flow rate was 1.0 mL x min(-1)
      and the column temperature was 25 degrees C. RESULT: All of the compounds were
      based--isolated. The linear ranges of swertiamarin, sweroside, gentiopicrin and
      oleanolic acid were 0.068 9-0.344 4(r = 0.999 2) , 0.001 1-0.014 0 (r2 = 0. 999
      8), 0.001 1-0.013 4 (r2 = 0.999 9) and 0.001 1-0.008 8 mg x mL(-1) (r2 = 0. 999
      6), respectively. CONCLUSION: The method is simple and accurate, which can be
      used for quality control of S. pseudochinesis.

PMID- 18330242
TI  - [Studies on chemical constituents from bark of Morus nigra].
AB  - OBJECTIVE: To investigate the chemical constituents in the barks of Morus nigra.
      METHOD: The nine compounds were isolated and purified by column chromatography
      over silica gel, LH -20 and preparative HPLC and their structures were identified
      by various spectroscopic methods. RESULT: The nine compounds were isolated and
      identified as olcancolic acid , apigenin, cyclocommunol, morusin, cyclomorusin,
      kuwanon C, daucosterol, ursolic acid, 63-sitosterol. CONCLUSION: Olcancolic acid,
      apingenin, cyclocommunol, morusin, cyclomorusin, kuwanon C, daucosterol were
      firstly isolated from the M. nigra.

PMID- 18330243
TI  - [Analysis of inflammatory reaction of atherosclerosis model].
AB  - OBJECTIVE: To analysis and evaluate the inflammatory reaction of atherosclerosis
      model in rabbits. METHOD: A model of atherosclerosis in rabbits was estabalished
      by injury with balloon and high cholesterol diet to observe the dynamic change of
      serum inflammation markers c-reactive protein, interleukin-1beta and tumor
      necrosis factor-a, and the relationship between severity of AS lesion and those
      change. RESULT: (1) The levels of TNF-alpha at 4 time points: 1, 6, 10 weeks and
      10 weeks + 1 day after balloon injury increased 1.6-fold, 2.2-fold, 4-fold, 2
      fold over concurrent control, respectively (P < 0.05, P < 0.01, P < 0.01, P <
      0.01), but no significant changes occurred during the observation. (2) At the end
      of the 6, 10 weeks and 10 weeks + 1 day, the levels of CRP were increased 3.5
      fold, 3.6-fold, 3.0-fold than concurrent control (P < 0.01, P < 0.01, P < 0.01),
      respectively. The levels were increased 2.4-fold at the end of the 6 weeks and
      4.1-fold at the end of the 10 weeks and reached the peak compared with the point
      of 1 week. (3) TNF-alpha and CRP showed a significant positive correlation with
      the MIT (correlation coefficients were found to be 0.61, 0.64, P < 0.01). (4) At
      the end of the 1, 6, 10 weeks, the model was provided with general pathological
      characteristics and the inflammatory reaction of earlier inflammatory reaction
      phase, fatty streak plaques phase, fibrous plaque phase respectively. CONCLUSION:
      The model was provided with early and medial phase typical feature of
      atherosclerotic lesion, and showed a significant positive correlation with the
      inflammatory factor expression. At the end of the 6 weeks, the formation of fatty
      streak plaques and obvious inflammatory reaction could be satisfied for the
      interference in forming process of AS from dimension of inflammatory and
      screening assays of drugs.

PMID- 18330244
TI  - [Ixeris sonchifolia induced vasoconstriction effect and its mechanism in rat
      thoracic aorta].
AB  - OBJECTIVE: To investigate the vasoconstriction effect of Ixeris sonchifolia in
      rat thoracic aortic rings and the underlying mechanisms. METHOD: I. sonchifolia
      10-160 g x L(-1) was cumulatively added into organ bath to observe the isometric
      tension of thoracic aortic rings with intact endothelium or denuded endothelium
      in basal tension, preconstricted by phenylephrine (PE) or potassium chloride
      (KCl), and thoracic aortic rings with intact endothelium preincubated frist with
      captopril, phosphoramidon and indomethacin, respectively, then preconstricted by
      PE and KCl. The response was recorded and expressed by "relative contraction".
      RESULT: Cumulative administration of I. sonchifolia 10-160 g x L(-1) did not
      affect the vasomotion of aortic rings with endothelium or without endothelium in
      basal tension. Exposure of intact endothelium rings preconstricted by PE or KCl
      to I. sonchifolia at concentration (20-160 g x L(-1) induced a significant
      constriction, which was inhibited by preincubation with captopril, but was not
      inhibited by preincubation with phosphoramidon or indomethacin. Exposure of
      endothelium-denuded rings preconstricted by PE or KCl to I. sonchifolia at
      concentration (10 to approximately 160 g x L(-1) did not effect the
      vasoconstriction. CONCLUSION: The results indicate that I. sonchifolia (20 to
      approximately 160 g x L(-1) can contract the rat thoracic aortic rings with
      endothelium. The effect of contraction may enhance angiotensin converting enzyme
      activity and promote endothelium to synthesize angiotensin II. It has no
      relationship to endothelin or thromboxane A2.

PMID- 18330245
TI  - [Study on bioavilability of oxymatrine-phospholipid complex in rats].
AB  - OBJECTIVE: To study the plasma concentration-time curve, pharmacokinetic
      parameters and bioavilability of oxymatrine-phospholipid complex and to compare
      with oxymatrine in rats. METHOD: Rats were given oxymatrine-phospholipid 100 mg x
      kg(-1). Blood samples were collected at different times after oral
      administration. The internal standard was cimetidine. Protein in plasma was
      precipitated with merhanol and centrifuged at high speed. The supernatant was
      directly injected and assayed by CE method. The running buffer was 0.04 mol x L(
      1) Tris-10 mmol x L(-1) sodium phosphate monobasic-40% isopropanol pH to 7.6 with
      phosphoric acid. The wavelength of detection was 205 nm. RESULT: The AUC of
      oxymatrine and oxymatrine-phospholipid complex were 4.52 mg x mL(-1) x h(-1) and
      6.21 mg x mL(-1) x h(-1), respectively. The oxymatrine-phospholipid
      bioavailability enhanced 1.4 times. CONCLUSION: It is concluded that after oral
      administration of oxymatrine-phospholipid complex in rats the bioavailability of
      oxymatrine is increased greatly. This is mainly due to an obvious improvement of
      the lipophilic property of oxymatrine-phospholipid complex compared with
      oxymatrine material and an increase in gastrointestinal absorption.

PMID- 18330246
TI  - [Effect of C21 steroidal glycoside from root of Cynanchum auriculatum on D
      galactose induced aging model mice].
AB  - OBJECTIVE: To study the effect of C21 steroidal glycoside (CSG) from the root of
      Cynanchum auriculatum from Jiangsu on D-galactose (D-gal) induced aging model
      mice. METHOD: D-gal aging mouse model was established by cervicodorsal region
      subcutaneous injection with D-gal once a day for eight successive weeks. The mice
      in the normal control group (NCG, non-modeled) and the model control group (MCG,
      modeled but untreated) were treated with 1% CMC-Na. The model mice in the low,
      middle and high-dose CSG and Vitamin E treated groups were treated with a dose of
      (10, 20, 40, 100 mg x kg(-1) per day, respectively. The SOD activity, MDA content
      and telomerase activity in serum, heart, liver and brain tissues of mice were
      measured. RESULT: CSG could obviously increase the SOD activity and decrease the
      MDA level in serum, heart, liver and brain tissues in D-gal aging mice (P <
      0.01). There was no significant difference between three CSG treated groups and
      Vitamin E treated groups. In comparison of telomerase activity between MCG and
      the treated groups, it was shown that there was a significant increase in serum
      in middle and high dose group, and in heart tissues in CSG and Vit E treated
      groups, but was not in liver and brain tissue. CONCLUSION: This study
      demonstrates that CSG can antagonize free radical injury, increase the SOD
      activity and decrease the MDA content of serum, heart, liver and brain in D-gal
      aging mice, and increase the telomerase activity in serum and heart tissues but
      not in liver and brain tissue.

PMID- 18330247
TI  - [Effects of puerarin on expression of nuclear factor kappaB after cerebral
      ischemia/reperfusion in rats].
AB  - OBJECTIVE: To investigate the activation of nuclear factor kappaB (NF-KB) and the
      influence of puerarin on it after cerebral ischemia-reperfusion in rats. METHOD:
      Cerebral ischemia-reperfusion injury was induced by 90 min of middle cerebral
      artery (MCA) occlusion and followed by 2, 6, 12, 24, 72 h reperfusion. Puerarin
      or saline was intra-peritoneally injected 1h before MCA occlusion and then the
      drugs were administered once every six hours. The infarct volume and brain edema
      were determined by TTC stain. Level of NF-kappaB P65 subunit was determined by
      immunohistochemistry and western blot. RESULT: Immunohistochemistry revealed the
      translocation of NF-kappaB. A time course of NF-kappaB induction in brain showed
      that NF-kappaB P65 subunit obviously increased at 6 h, peaked at 24 h and then
      decreased by 72 h post-reperfusion. Puerarin decreased the level of NF-kappaB at
      24, 72 h after reperfusion. There was a decrease trend in brain infarct volume
      between puerarin and control. CONCLUSION: NF-kappaB is translocated and its level
      is increased after ischemia-reperfusion. Puerarin may attenuate the ischemia
      reperfusion injury through inhibition of NF-kappaB activation.

PMID- 18330248
TI  - [Effects of paeoniflorin on pathological changes in global brain ischemia model
      rats].
AB  - OBJECTIVE: To explore the effects of paeoniflorin on blood brain barrier and
      pathological changes in brain ischemia. METHOD: Mice were divided into sham
      operation group, model group, positive control group-Deng zhanhua tablet group
      and three different dose (high, middle, low-dose) groups of paeoniflorin. The
      neurological symptoms of rats were observed. The SOD of ischemic brain tissue,
      MDA BBB and EAA contents were determined. The ultrastructure on the brain cells
      was inspected by transmission electron microscope. RESULT: Paeoniflorin had the
      protetive effects on 4VO model of total cerebral ischemia. Paeoniflorin could
      obviously increase SOD content, reduce MDA content in rat brain-tissue and
      alleviate oxidative stress damage by cerebral ischemia on rat brain. Paeoniflorin
      could improve pathological changes of cell nuclear, perikaryon, mitochondria and
      myelin sheath, which was the morphologic basis of the protective effect on
      ischemia. Paeoniflorin could alleviate the incrense of EAA content caused by and
      hypoxia and inhibit the excitatory neural toxicity by EAA. CONCLUSION:
      Paeoniflorin has the protection effect on the brain edema after cerebral
      ischemia, the oxidative stress damage on brain tissue, the ultrastructure lesions
      of cells and the BBB. The protective mechanism may be related to inhibiting
      intracellular calcium overload, anti-free radical and reducing EAA content.

PMID- 18330249
TI  - [Absorption of coptisine chloride and berberrubine across human intestinal
      epithelial by using human Caco-2 cell monolayers].
AB  - OBJECTIVE: To study the absorption of coptisine chloride (COP) and berberrubine
      (BRB) as chemical constituents of some traditional Chinese medicines in human
      intestinal epithelial. METHOD: By using Caco-2 (the human colonic adenocarcinoma
      cell lines) cell monolayers as an intestinal epithelial cell model, the
      permeability of COP and BRB were studied from apical side (AP side) to
      basolateral side (BL side) or from BL side to AP side. The two alkaloids were
      measured by reversed-phase high performance liquid chromatography (HPLC) coupled
      with UV detector. Transport parameters and apparent permeability coefficients
      (P(app)) were then calculated and compared with those of propranolol and
      atenolol. P(app) values were also compared with the reported values for model
      compounds (propranolol and atenolol). RESULT: The P(app) values of COP, BRB were
      (1.103 +/- 0.162) x 10(-5), (1.309 +/- 0.102) x 10(-5) cm x s(-1 from AP side to
      BL side, and (0.300 +/- 0.041) x 10(-5) and (1.955 +/- 0.055) x 10(-5) cm x s(-1)
      from BL side to AP side, respectively. Their P(app) values were identical with
      those of propranolol [(2.23 +/- 0.10) x 10(-5 cm x s(-1)], which is a
      transcellular transport marker and as a control substance for high permeability.
      On the other hand, the efflux transport of BRB was higher 1.49 times more than
      its influx transport with 0.67 rate of P(app A-->B)/P(app B-->A). But P(app A-
      >B)/P(app B-->A value of COP was 3.67, which suggested that the efflux transport
      have not been involved in its absorbed mechanism in Caco-2 cells monolayers.
      CONCLUSION: COP and BRB can be absorbed across intestinal epithelial cells, and
      they are completely absorbed compounds. BRB may have been involved in efflux
      mechanism in Caco-2 cells monolayers model from the basolateral-to-apical
      direction.

PMID- 18330250
TI  - [Determination of cinnamic acid in rat plasma after oral administration of subing
      orally disintegrating tablets and study of its pharmacokinetics behavior].
AB  - OBJECTIVE: To develop a RP-HPLC method for determination of cinnamic acid in rat
      plasma. METHOD: The plasma samples were acidified with acetic acid and extracted
      with chloroform. Cinnamic acid was separated on a Kromasil C18 column (250 mm x
      4.6 mm, 5 microm) eluted with a mobile phase of methanol-acetonitrile-water
      glacial acetic acid (25:20:55:0.3) at a flow rate of 1.0 mL x min(-1) and room
      temperature with UV detection at 278 nm, carbamazepine as internal standard.
      RESULT: The standard curve was linear over the range of 4.0 to approximately 400
      ng x mL (-1) r = 0..99 9. The LOQ was 4.0 ng x mL(-1), the mean extraction
      recovery of the spiked samples at low, middle and high levels was 86.4%, while
      the mean method recovery was 100.3%. The RSD of intra-day and inter-day were both
      less than 6.0%. CONCLUSION: The method was sensitive, specific, accurate and
      precise, which was used to study the pharmacokinetic profile of cinnamic acid in
      rat plasma after oral administration of the Subing orally disintegrating tablets.

PMID- 18330251
TI  - [Study on effect of different combinations of traditional Chinese medicine
      preparation active parts on metabolism of puerarin in plasma of rats].
AB  - OBJECTIVE: To build an experimental method to determine the content of puerarin
      in plasma, observe the effect of different combinations of traditional Chinese
      medicine preparation active parts on metabolism of puerarin in plasma of rats
      suffering cerebral ischemia attack after being orally administered the main
      active parts of Yangyin Tongnao granules. METHOD: Absorption of puerarin in
      plasma was extracted by acetonitrile. Using hydroxybenzoate as interior standard,
      methanol-0.5% acetic acid water solution as mobile phase, ODS C(18)
      chromatography column (4.6 mm x 150 mm, 5 microm) as stationary phase, puerarin
      was detected at 248 nm. RESULT: There is a good linear relationship for puerarin
      in the range 0.025-3.2 microg x mL-1, RSD < 10%, and the average recovery is
      97.6%. CONCLUSION: The method is sensitive, reliable, and can be well applied in
      this experiment. It can provide a method for determination of active components
      in TCM preparation in vitro. Different compatibility influences metabolism of
      components.

PMID- 18330252
TI  - [Pharmacokinetic study on baicalin of Qingkailing injection in rats].
AB  - OBJECTIVE: Studying the metabolic pharmacokinetic of baicalin of Qingkailing
      injection in rat, to search for effector substance of Qingkailing injection in
      vivo. METHOD: Qingkailing sterile injection powder was given by caudal vein, then
      blood, liver and lung were collected in various time, the concentration of
      baicalin from samples were determined by HPLC-MS. Pharmacokinetic evaluation was
      carried out using the 3P87. RESULT: After Qingkailing injection, Baicalin was
      consistent with two-compartment model in rat. 45 min, the concentration of
      baicalin in hepatic tissue reached maximum, followeded by decrease sharply, 120
      min began to rise slowly, present double hump phenomenon. In lung, baicalin
      concentration was far more than in liver, was eliminated more slowly, but they
      have the same t(max). CONCLUSION: After Qingkailing injection, baicalin
      distributed quickly to liver and lung, baicalin is one of effector substance of
      qingkailing injection in vivo. Baicalin might have hepatoenteral circulation.

PMID- 18330253
TI  - [Effects of AST and ASI on metabolism of free radical in senescent rats treated
      by HC].
AB  - OBJECTIVE: To study the effects of Astragaloside (AST) and Astragalus Saponin I
      (ASI) on metabolism of free radical and immune function in senescent rats treated
      by HC. METHOD: Hydrocorisone (HC) was used to estabilsh the aging model in rats.
      The content of molondialdehyde (MDA), glutathoine (GSH) and oxidized glutathoine
      (GSSG) in liver and brain was detected according to kit. The activity of Mn
      superoride dismulase (Mn-SOD) and catalase (CAT) was also surveyed by kit.
      Concanavalin (ConA) was used to detect the proliferation and interleukin-2 (IL-2)
      production of splenocytes. RESULT: Compared with HC control, AST and ASI could
      decrease the content of MDA, GSH and GSSG in liver and brain, increase the
      activity of Mn-SOD and CAT, and promote the proliferation and interleukin-2 (IL
      2) activity of splenocytes. CONCLUSION: AST and ASI could delay the aging effect
      in rats treated by HC, and its mechanism maybe the antioxidant and regulating
      immunity.

PMID- 18330254
TI  - [Investigation of Coptis chinensis on jaundice of glucose-6-phosphate
      dehydrogenase (G6PD) deficient neonates from Guigang, Guangxi province].
AB  - OBJECTIVE: To investigate the effect of Coptis chinensis on jaundice of G6PD
      deficient neonates. METHOD: 122 G6PD deficient neonates with jaundice who were in
      People' s Hospital of Guigang of Guangxi province from January 1999 to October
      2004 were divided into two groups: C. chinensis group (62 neonates with C.
      chinensis administration before jaundice' s appearance) and none C. chinensis
      group (60 neonates without C. chinensis administration before jaundice' s
      appearance). The initial time, duration of jaundice, hemoglobin and serum
      bilirubin level and the incidence of kernicterus were analyzed between the two
      groups. RESULT: The initial time of jaundice is significantly later and the
      duration of jaundice is markedly shorter in the neonates with C. chinensis than
      that without C. chinensis. Simultaneously, the level of hemoglobin is
      significantly increased, and there is a low tendency of serum total bilirubin and
      direct bilirubin level in C. chinensis group as compared to that in none C.
      chinensis group. Moreover, there is no kernicterus in C. chinensis group and no
      difference in the treating result out of hospital between the two groups.
      CONCLUSION: Our results do not support the view that C. chinensis could aggravate
      jaundice of G6PD deficient neonates.

PMID- 18330255
TI  - [Synergistic interactions of TRAIL and paclitaxel on the laryngeal squamous
      carcinoma cell line in vitro].
AB  - OBJECTIVE: To investigate the synergistic cytotoxicity of TRAIL and paclitaxel on
      laryngeal squamous carcinoma cell line Hep-2. METHOD: Hep-2 cells were exposed to
      various concentrations of TRAIL and paclitaxel respectively or jointly. The
      inhibition rate was measured by CCK-8 assay. The apoptosis rate and the
      expressions of DR4, DR5, DcR1 and DcR2 in Hep-2 cells were detected by flow
      cytometry methods. RESULT: Hep-2 cells were resistant to apoptosis induced by
      TRAIL. Paclitaxel could enhance its sensitivity to TRAIL by up-regulating the
      expressions of TRAIL death receptors in Hep-2 cells. CONCLUSION: The resistance
      of Hep-2 cell to TRAIL could be overcome by paclitaxel. TRAIL and paclitaxel have
      synergistic killing effects on Hep-2 cells, so they might have a promising
      prospect in clinical therapy of laryngeal squamous carcinoma.

PMID- 18330256
TI  - [Expression and prognostic significance of cyclooxygenase-2 in supraglottic
      laryngeal squamous cell carcinomas].
AB  - OBJECTIVE: To study the expression and prognostic significance of cyclooxygenase
      2 (Cox-2) in supraglottic laryngeal squamous cell carcinomas (SGLSCC) and
      identify the relationship between Cox-2 and angiogenesis and the roles of Cox-2
      in SGLSCC as a biological marker. METHOD: Eighty-eight primary SGLSCC patients
      received surgical treatment were studied by immunohistochemical staining, and
      reverse transcription-polymerase chain reaction (RT-PCR) technique. RESULT: The
      percentage of Cox-2-positive cells was 94.3% (83/88) in SGLSCC whereas there was
      no immunostaining in the all cells of normal mucosa of paracarcinoma. Cox-2
      expression was higher in well-differentiated tumors compared with poorly
      differentiated SGLSCC. The relative concentration of Cox-2 mRNA was 141.871 +/-
      20.5435 in SGLSCC and 17.031 +/- 2.2597 in normal paracarcinoma mucosa (P <
      0.01). It was significantly higher in SGLSCC than in normal paracarcinoma mucosa.
      In SGLSCC, only pathological grading and the percentage of Cox-2-positive cells
      had significant correlation (P < 0.01). And not only the percentage of Cox-2
      positive cells but also Cox-2 intensity had significant correlation with
      microvessel density (MVD) (P < 0.01). Kaplan-Meier survival analysis showed there
      had significant relationship between Cox-2 intensity and cumulative survival rate
      of SGLSCC patients (P < 0.05). But the percentage of Cox-2-positive cells was
      different (P > 0.05). Cox's regression analysis indicated that Cox-2 intensity
      were significantly independent prognostic factors (P < 0.01). CONCLUSION: Cox-2
      expression maybe relate to the carcinogenesis and progress in tumors especially
      in well-differentiated ones; The changes of Cox-2 expression are synchronous with
      MVD. Cox-2 intensity is a significantly independent prognostic factor. So Cox-2
      may be an effective target of prevention, therapy and prognostic evaluation for
      laryngeal carcinoma and other head and neck squamous cell carcinomas (HNSCC).

PMID- 18330257
TI  - [Relevance of Endoglin (CD105) VEGF and p53 with invasion metastasis and
      prognosis of laryngeal carcinoma].
AB  - OBJECTIVE: To evaluate the clinical significance of microvessel density (MVD) and
      investigate the relationship of Endoglin (CD105), VEGF and p53 protein and their
      significance of clinical pathology. METHOD: Pathologic paraffin-embedded tissues
      and clinic data of 40 patients with primary squamous cell carcinoma of larynx
      were studied. Serial sections were respectively stained with Endoglin (CD105),
      VEGF and p53 by immunohistochemistry and its expressions were investigated.
      Microvessel density (MVD) highlighted by Endoglin (CD105) were counted according
      to a standard protocol. RESULT: Endoglin (CD105) expression in tumour tissue was
      significantly higher than in normal mucosa (P < 0.05). The mean MVD value for
      Endoglin (CD105) was 14. 90 +/- 7.40. The mean CD105-MVD value of T3 and T4
      tumours showed a significantly higher staining than that of T1 and T2 tumours;
      The mean CD105-MVD value of tumours with metastasis was also higher than that of
      tumours with no metastasis (P < 0.05); The expression of VEGF was observed in
      cytoplasm of tumour cell and its positive rate was 77.5% in laryngeal carcinoma,
      which was significantly correlated with TNM stage and pathological
      differentiation of laryngeal carcinoma (P < 0.05). The expression of p53 protein
      was mainly observed in nucleolus of tumour cell and its positive rate was 67.5%,
      which was significantly correlated with metastasis of lymph node. Positive
      relevance was found between CD105-MVD and VEGF (r = 0.641, P < 0.01); Positive
      relevance was also found between CD105-MVD and p53 (r = 0.534, P < 0.01).
      CONCLUSION: Endoglin (CD105) is a marker of tumour angiogenesis for its
      significant associated with active angiogenesis in laryngeal carcinoma. The study
      shows that CD105-MVD in laryngeal carcinoma is an independent indicator of
      predicting invasion, metastasis and recurrence, and evaluating prognosis of
      malignant tumours. CD105-MVD, VEGF and p53 could be important indicators to
      evaluate invasion, metastasis and recurrence of laryngeal carcinoma.

PMID- 18330258
TI  - [Effects of procaine on human nasopharyngeal carcinoma cell strain CNE-2Z].
AB  - OBJECTIVE: To study the effects of procaine on human nasopharyngeal carcinoma
      cell strain CNE-2Z. METHOD: CNE-2Z cells-cultured in vitro-were exposed to
      different concentration procaine and different time. Its growth characteristic
      were studied by using MTT assay and flow cytometry. The expression of p16 and
      RASSF1A mRNA were analyzed by RT-PCR. RESULT: Procaine could inhibit the
      proliferation of CNE-2Z cells and the effects were in dose- and time-dependent
      manners. Procaine also arrested CNE-2Z cells in G1 phase of cell cycle. The
      expression of RASSF1A mRNA was up-regulated in CNE-2Z cells treated with
      procaine, but no obvious change was found in the expression of p16 mRNA.
      CONCLUSION: Procaine could inhibit cell growth and up-regulate the expression of
      RASSF1A mRNA, which may play an important role in CNE-2Z cells' proliferation
      inhibition induced by procaine.

PMID- 18330259
TI  - [Peri-uvulopalatopharyngoplasty changes on the relationship between arousal and
      nocturnal heart rate variability in patients with OSAHS].
AB  - OBJECTIVE: To study the relationship between arousal and nocturnal apnea-hypopnea
      syndrome (OSAHS). METHOD: Fifty four patients with OSAHS underwent overnight
      polysomnography (PSG) were enrolled, An hour continuous PSG monitoring in non
      rapid eye movement (NREM) was recorded for all patients. The mean heart rate (HR)
      in 10 s before each arousal and the peak HR IN 10 s after arousal were compared,
      and the breathing disorder related arousal index (B-ArL) and pulse rate rise
      index (PRRI) were calculated at this time, and then a correlation analysis were
      performed and then Delta HR at apnea termination between these events were
      compared. RESULT: the peak HR in 10 s after arousal onset was significantly
      higher than the mean HR in 10 s before arousal onset, and B-Arl was positively
      correlated to PRRI. the Delta HR of events with EEG arousal at apnea termination
      was higher than those without EEG arousal. CONCLUSION: The results indicate that
      arousal can influence the function of cardiovascular regulation; Frequent arousal
      is one of the main causes of the cardiovascular consequences in OSAHS patients.
      Operation can reduce these influences.

PMID- 18330260
TI  - [Effects on distant metastasis of misdiagnosis of nasopharyngeal carcinoma].
AB  - OBJECTIVE: To investigate the effects of situation of misdiagnosis of
      nasopharyngeal carcinoma (NPC) on distant metastasis. METHOD: The history of
      diagnosis and treatment of 85 newly diagnosed cases with nasopharyngeal carcinoma
      were studied by using itemized questionnaire purposely; 433 patients with
      different prognosis were analyzed retrospectively for the misdiagnoses and
      mistreatment, including surgical biopsy in the neck. RESULT: (1) The rate of
      misdiagnosis of 85 patients was 72.64%, and the percentage decreased as the level
      of the hospitals increased; the majority of the patients (77.36%) were diagnoses
      within 1 month after the first symptom had appeared; the number of diseases
      misdiagnosed was 20, most common of which were lymphnoditis, tuberculosis of
      lymph node and secretory tympanitis; (2) Our data showed that among 433 patients
      analysed retrospectively, 60 cases had undergone surgical biopsy in the neck, 75%
      of whom had never received nasopharyngeal biopsy; 43 cases had underwent
      nasopharyngeal biopsy after the pathological diagnosis as metastatic carcinoma of
      neck biopsy (71.67%) and the rest (20.0%) received radiotherapy directly or after
      negative nasopharyngeal biopsy for merely 1 to 4 times; of those 43 cases who
      were diagnosed as NPC by nasopharyngeal biopsy, 79.17% got positive results at
      first sampling. (3) Rate of misdiagnosis and mistreatment including surgical
      biopsy in the neck of patients who had been tumor-free for 5 years or above was
      significantly lower than that of those who experienced distant metastasis after
      or before treatment (P < 0.05). CONCLUSIONS: Misdiagnosis and mistreatment
      including biopsy by surgery of neck is common even in high-grade hospitals; it is
      doctor that is responsible for this situation; the high occurrence rate of
      misdiagnosis and mistreatment, biopsy by neck surgery, especially the delayed
      treatment after the neck biopsy are the factors that contribute to distant
      metastasis of NPC.

PMID- 18330261
TI  - [Hyoid suspension with repose system combined with UPPP in severe OSAHS patients:
      short-term results].
AB  - OBJECTIVE: To explore the effect of a comprehensive surgical approach of hyoid
      suspension with Repose system plus uvulopalatopharyngoplasty (UPPP) on the
      treatment of severe obstructive sleep apnea hypopnea syndrome (OSAHS). METHOD:
      Twelve patients with severe OSAHS (AHI > 40) diagnosed by polysomnography, were
      determined for the obstruction in both the velo-pharyngeal and the hypopharynx by
      preoperative physical examination, fiberoptic pharyngo-laryngoscopy. Two cases
      were given continuous airway pressure via nose, seven days before operation and
      then were performed hyoid suspension plus UPPP. The follow up was 3 months
      postoperatively. The pair T test was used to compare the preoperative and
      postoperative results by SPSS11.0 for windows. RESULT: At postoperative 3 month,
      there were statistically significance between preoperative and postoperative
      measurement in all. Mean AHI decreased from preoperative 69.28 +/- 6.50 to
      postoperative 19.77 +/- 9.23, lowest mean oxygen saturation increased from 65.25 
      /+ 3.14 to 90.17 +/- 2.86. Snoring and sleep apnea disappeared or lessened, with
      the disappearance or decrease of lethargy at daytime. No severe complication
      occurred. CONCLUSION: Comprehensive surgical approach of hyoid suspension with
      Repose system plus UPPP is effective surgical approach for patients with severe
      OSAHS who suffered from oropharyngeal and hypopharyngeal obstruction in short-
      term result.

PMID- 18330262
TI  - [Inhibit affection of resveratrol on the growth of Hep-2 cell line].
AB  - OBJECTIVE: To study the inhibitory effect of resveratrol on growth of human
      laryngeal cancer cell line, Hep-2. METHOD: Count cell number under microscope,
      MTT assay was used to determine the cell growth inhibitory rate. Soft agar colony
      forming experiment was performed to observe the proliferation ability, before or
      after resveratrol treatment. RESULT: Resveratrol was able to depress cell growth
      and inhibit cell proliferation. CONCLUSION: Resveratrol strongly inhibit Hep-2
      cell proliferation in a time- and dose-dependent manner.

PMID- 18330263
TI  - [Clinico-pathological study of contralateral lymph node metastasis in pyriform
      sinus carcinoma].
AB  - OBJECTIVE: To study the related factors of contralateral lymph node metastasis in
      pyriform sinus carcinoma. METHOD: Fifty-three patients with pyriform sinus
      carcinoma underwent simultaneous neck dissection from Oct. 1993 to Oct. 1999 were
      collected. Transparent lymph node selection and continuous slicing method were
      used on the postoperative specimens to observe the status of cervical lymph node
      metastasis. The relationship between contralateral lymph node metastasis and
      clinico-pathological factors, ipsilateral neck metastatic status were analyzed by
      the follow-up data. RESULT: Cervical lymph node metastatic rate was 79.2% in 53
      patients with pyriform sinus carcinoma. Contralateral cervical lymph node
      metastatic rate was 35.8%. Contralateral neck metastasis was closely related with
      clinical N stage, cell differentiation, fused metastasis and extracapsular spread
      of ipsilateral neck. CONCLUSION: Contralateral neck dissection should be
      undertaken in patients with N2,3, moderate and low cell differentiation, or fused
      fused metastasis and extracapsular spread of ipsilateral neck.

PMID- 18330264
TI  - [Resection of nasopharyngeal angiofibroma using by midfacial degloving approach
      and modified maxillectomy].
AB  - OBJECTIVE: To explore the feasibility of treatment on angiofibroma patients with
      stage III, IV by midfacial degloving approach and modified maxillectomy. METHOD:
      From Feb. 2001 to Aug. 2004, midfacial degloving approach and modified
      maxillectomy was used for treating 7 angiofibroma patients with stage III, IV.
      Using Fisch stage: Five cases were in stage III, 2 cases were stage IV; 2 cases
      with stage III accepted midfacial degloving approach and modified maxillectomy.
      Five cases accepted midfacial degloving approach and Le fort I approach (stage
      III, 3 cases; stage IV, 2 cases). One patient accepted the combined therapy of
      facial approach and cranium approach. 6 cases accept the embolization of the
      artery which feed the tumor (2 cases in stage IV, 4 cases in stage III). RESULT:
      The blood loss was (600 +/- 324) ml in operation, the blood loss in operation of
      patients with selective preoperative embolization was (483 +/- 165) ml. The blood
      loss of one case with no selective preoperative embolization was 1300 ml. The
      operating time was 129 +/- 22 min. The pathology of 7 cases was nasopharyngeal
      angiofibroma. For 30 to 72 months follow-up, No tumor recurrence were observed,
      one case in stage III accepted the selective preoperative embolization got the
      tumor recurrence 1 year after the surgery. After the second surgery, no tumor
      recurrence were seen till now. CONCLUSION: For the patients in stage III, IV,
      midfacial degloving approach and modified maxillectomy is not only good for
      radical excision, curtating the operating time and blood loss, but also good for
      the cosmetic outlook and functional recovery. The selective preoperative
      embolization has a good significance on reducing the operating blood loss and
      tumor recurrence rate.

PMID- 18330265
TI  - [Effect of quercetin on proliferation and apoptosis of human nasopharyngeal
      carcinoma HEN1 cells].
AB  - OBJECTIVE: To investigate the effect of quercetin (Que) on HEN1 cells, a kind of
      human nasopharyngeal carcinoma cells. METHOD: Inhibition rate of quercetin on
      HEN1 was assayed by MTT method, cell apoptosis by flow cytometry (FCM), Caspase-3
      expression of each group were determined by colorimetry set. RESULT: The
      inhibition of quercetin on HEN1 cells was shown in the dose-dependent (r = 0.709,
      P < 0.05) and time-dependent manner (r = 0.703, P < 0.01). The ratio of apoptotic
      and necrosis cells increased accompanied with added quercetin concentration. Cell
      cycle was specificly arrested inG2/M phase. Apoptosis cusp was revealed by FCM.
      While the activity of caspase-3 were also significantly upregulated in five
      groups after quercetin compared to control (P < 0.05). CONCLUSION: Quercetin can
      activate the expression of Caspase-3 and induce the apoptosis of HEN1 cells
      through mitochondrion-depended pathway.

PMID- 18330266
TI  - [Spectral power distribution and quantum yield of Sm3+-doped bismuth tellurite
      glass under the excitation of violet LED].
AB  - A new method for measuring the spectral power distribution in Sm3+-doped bismuth
      tellurite glass with higher refractive index and lower phonon energy by using
      integrating sphere was introduced and designed for the first time. Fluorescence
      measurement system was constituted by integrating sphere of 10-inch diameter,
      which was connected to a DDC detector. A standard halogen lamp was used to
      calibrate the measurement system and the auxiliary standard halogen lamp was
      employed for collating inner change in integrating sphere. The total radiant
      flux, total luminous flux and total quantum yield were calculated by luminous
      flux distribution and photon distribution, which were derived from spectral power
      distribution, and the values were 55 microW, 0.02 lm and 4.07%, respectively. In
      the present paper, the integrating sphere-method was applied to measure the
      luminescence parameters of the multichannel transition emissions in Sm3+, and it
      was considered as an accurate way to characterize luminescence parameters for
      luminescence and laser material.

PMID- 18330267
TI  - [Spectral characteristics of optical storage material CaS : Eu, Sm].
AB  - As a typical optical storage material, CaS : Eu, Sm powders were prepared by wet
      method in a reduced atmosphere. XRD, emission spectrum, excitation spectrum,
      photostimulated spectrum, thermal spectrum, and decay curve were measured. The
      XRD indicates that the lattice of CaS : Eu, Sm was formed at 1050 degrees C.
      Spectra analysis results show that UV can excite the sample as an information
      input source. When excited by ultraviolet lamp and then stimulated by 980 nm
      laser, the same luminescence with peaks at 635 nm. The photostimulated emission
      decayed rapidly at first and then slowly. The trap level is deep and can make
      electrons stable in the trap. The optical storage mechanism of CaS : Eu, Sm is
      discussed.

PMID- 18330268
TI  - [Mixing and quenching of Rb 5PJ states induced by collisions with He atoms and N2
      molecules].
AB  - The collisional energy transfer process Rb(5PJ)+M, where M= He, N2, under gas
      cell conditions has been investigated. The Rb(5P3/2) state was excited by a diode
      laser. The direct 5P3/2-->5S1/2 fluorescence and the sensitized 5P1/2-->5S1/2
      fluorescence as a function of quenching gas pressure were measured. The 5P3/2 and
      5P1/2 states are separated by 238 cm(-1). The closest other states are >6500 cm(
      1) or >28 KT. Neglect of these other states should be an excellent approximation.
      In the experiment the Rb density was 4.5 x 10(11) cm(-3). Using radiation
      trapping theory the effective radiative rate=Gammae5P3/2-->5S1/2 2.47 x 10(7) s(
      1) was obtained. For quenching by He only electronic to translational energy
      transfer is possible. However, in the N2 case, electronic to vibrational or
      rotational transfer is important. The Rb(5P3/2) state is 13 cm(-1) lower than the
      N2[X'Sigmag+ (V= 5, J= 11)]state; this energy gap is near resonant. The authors
      have not attempted to directly observe this possible E-R quenching channel Using
      a two-state rate equation model the transfer rate coefficients from Rb(5PJ) were
      obtained. The rate coefficient (k21He) for 5P3/2-->5P1/2 transfer in collision
      with He is 2.61 x 10(-12) cm3 x s(-1). By comparing the direct and sensitized
      fluorescence intensities for He and N2 case, and fitting the experimental results
      to the rate equation analysis, the authors estimate that the rate coefficient
      (k21N2) for 5P3/2-5P1/2 transfer in collision with N2 is 2.36 x 10(-11) cm3 x s(
      1). The E-V quenching rate coefficient (kN2) of the 5PJ state is 1.44 x 10(-10)
      cm3 x s(-1). The authors found find that the rate coefficient kN2 is about 6
      times larger than the k21N2. The assumption that the Cs-N2 energy transfer occurs
      primarily in collinear collision geometry is supported. The results are discussed
      in relation to those of other experiments.

PMID- 18330269
TI  - [Spectrum studies of ignition characteristic in quick reaction of benzene].
AB  - A new optical spectroscopy system consisting of a monochromator, photomultiplier
      tubes (PMT), piezoelectric pressure sensor and digital phosphor oscilloscope was
      established to study spectrum and ignition delay time of benzene in quick
      reaction in a high temperature shock tube. A new method of determining ignition
      delay time of energetic materials behind incident shock wave is proposed. Several
      important products, such as H, C2 and CH, were determined in sequence of
      emergence time. The reaction mechanism of formation of carbon was introduced when
      benzene was driven under shock compression. The results indicate that in spite of
      the variety of Mach number, atom H always emerged first, indicating that the
      pyrolysis of benzene started with C-H bond instead of C-C bond. The results show
      that applying spectrum techniques can preferably study the ignition
      characteristic of benzene in quick reaction. Measuring ignition delay time by
      means of a prior emerged intermediate product (atom H) is more accurate than that
      with white color technique widely used home and abroad, and furthermore, can
      obviously reduce the times of experiment.

PMID- 18330270
TI  - [Synthesis and characterization of broadband IR-to-visible upconversion material
      caS : Ce, Sm by low-temperature combustion synthesis method].
AB  - Broadband IR-to-visible upconversion material CaS : Ce, Sm was synthesized for
      the first time by the low-temperature combustion synthesis (LCS) method. The
      effect of the rare earth dopant concentration on the upconversion properties was
      studied. XRD analysis shows that the sample features the cubic CaS crystal
      structure. The excitation spectrum of the sample is in the range of 200-500 nm,
      i. e. ultraviolet light or the visible light can excite the sample effectively to
      complete the "charged" process, and the excitation effect of the visible light is
      dominant. The IR sensitivity spectrum of the sample is in the range of 800-1 400
      nm, indicating that CaS : Ce, Sm possesses the broadband IR-to-visible
      upconversion effect. The IR-to-visible upconversion spectrum of the sample is a
      broadband spectrum in the range of 450-650 nm, with two adjacent emission peaks
      at 513.4 and 572 nm, resulting from the transitions of Ce3+2T2g(5d)-->2F5/2 (4f)
      and the transitions of Ce3+2T2g(5d)-->2F7/2 (4f), respectively.

PMID- 18330271
TI  - [Measurement and analysis of discharge current in dielectric barrier glow
      discharge at atmospheric pressure].
AB  - Dielectric barrier discharge has become a hot issue in low temperature plasma
      research field because of wide prospect for its application in industry. In the
      present paper, an uniform glow discharge was realized in atmospheric pressure
      helium with a parallel planar dielectric barrier discharge device and an uniform
      plasma was generated in helium at atmospheric pressure. Electrical method was
      used to separate the discharge current from the total current signal and the
      waveform of discharge current could be obtained. The relations among the
      discharge current, applied voltage, gap voltage and wall charge during the
      uniform glow discharge were used to analyze the dynamical behavior of wall
      charges during their accumulation. The results show that the wall charges were
      mainly accumulated during the existence of discharge current pulse, while the
      quantity of wall charges continued to increase until the gap voltage changed its
      polarity after the disappearance of discharge current pulse, and finally the
      quantity of wall charges decreased until the next breakdown. These experimental
      results are important for the further study of wall charges' effect in the
      dielectric barrier glow discharge and its application in industry.

PMID- 18330272
TI  - [Measurement of N2+ rotational temperature in air dielectric barrier discharge].
AB  - The rotational lines of the first negative band system of N2+ were observed in
      air dielectric barrier discharge by using liquid electrodes. The rotational
      temperature was estimated by the J number of the lines with the maximum intensity
      in rotational spectrum. The rotational temperature was kept at a constant with
      increasing the applied voltage when the gas pressure was in the range of 10.133
      60.795 kPa. The results are of great importance to the model foundation and the
      application of dielectric barrier discharge in air.

PMID- 18330273
TI  - [Luminescence characteristics of terbium-doped nanocrystalline zinc oxide].
AB  - It is known that zinc oxide is a kind of important functional and novel material
      of II-VI wide bandgap semiconductor (Eg = 3.37 eV), and has excellent
      microstructural, chemical and physical properties. The intensity of
      photoluminescence, luminescence peak positions and other kinds of luminescence
      properties of ZnO : RE3+ nanocrystalline are strongly dependent on the annealing
      temperature and time, and the concentration of the doping rare earth ions.
      Terbium-doped zinc oxide nanocrystalline were successfully prepared by sol-gel
      process at different annealing temperature. Photoluminescence spectrum (PL),
      photoluminescence spectrum excitation(PLE) and X-ray diffraction pattern(XRD) of
      nanocrystalline ZnO : Tb3+ with excitation wavelength 368 nm were measured at
      room temperature. The emission from 5D4-->7F6 (485 nm), 5D4-->7F5 (544 nm), 5D4-
      >7F4 (584 nm) and 5D4-->7F3 (620 nm) of Tb3+ ions, and the wide visible band of
      ZnO were observed. Photoluminescence intensity of nanocrystalline ZnO : Tb3+ on
      the doping concentration and annealing temperature was given, and it was found
      that the optimal dopant concentration and annealing temperature were 4 at% and
      600 degrees C, respectively. The luminescence process of Tb3+-doped zinc oxide
      nanocrystalline was investigated by using PL and XRD. The photoluminescence
      mechanism suggests that there is energy transfer between ZnO nanocrystalline
      hosts and the doping Tb3+ centers.

PMID- 18330274
TI  - [Thermal decomposition of 2-H-heptafluoropropane at different temperatures].
AB  - The thermal decomposition processes of 2-H-heptafluoropropane were investigated
      during a 30 second reaction time and at temperatures of 400, 500, 600, 700 and
      800 degrees C using fast pyrolysis method and Fourier transform infrared spectra
      (FTIR) and gas chromatography/mass spectrometry (GC/MS) analytical techniques.
      The results indicate that the reaction temperatures have the obvious effects on
      the thermal decomposition of 2-H-heptafluoropropane. The 2-H-heptafluoropropane
      is steady at first three temperatures, whereas starts to obviously decompose at
      700 degrees C and undergoes intense decomposition at 800 degrees C. At the same
      time, coke formation was observed on the surface of the reactor at 800 degrees C.
      Moreover, three cyclocompounds, 1,2-bis(trifluoromethyl) perfluoroindane,
      perfluoro(1-ethylideneindane) and octafluoronaphthalene, were for the first time
      discovered in the products of thermal decomposition at 800 degrees C. This
      demonstrates that 2-H-heptafluoropropane experiences not only simple
      decomposition, but also cyclization and the polymerization reactions under high
      temperature thermal decomposition conditions.

PMID- 18330275
TI  - [Effects of thermostress on the plasma membrane permeability of desert moss
      Tortula desertorum examined by in-situ micro-FTIR analysis].
AB  - A technique based on Fourier transform infrared microscope (FT-IRM) was developed
      to detect the corresponding changes in chemical composition associated with
      thermostress among aging tissues of the desert moss Tortula desertorum. The
      results indicated that wild leaves could accelerate the rate of carbohydrate
      synthesis and decrease the permeability of plasma membrane during heating at 45
      degrees C for 1 h. Those biological responses can alleviate the damage of heat
      stress, so called thermotolerance. And the ability has a positive relation to the
      leaf age among various wild leaves. However, the secondary protonema and leaves,
      cultivated in artificial incubator, were unable to adapt the change of
      temperature immediately and the permeability of cellular membranes was increased.

PMID- 18330276
TI  - [FTIR spectroscopic explorations of freshly resected thyroid malignant tissues].
AB  - In the present paper, 17 cases of freshly resected malignant thyroid tissue
      samples and 23 cases of benign thyroid tissue samples were characterized using
      FTIR spectroscopy with an ATR probe. Statistic analysis indicated that the FTIR
      spectra of cancerous tissue were significantly different from those of benign
      tissue. In comparison with normal tissues, the FTIR spectra of malignant thyroid
      tissues possess the following features: (1) Variation of bands related to
      protein: Amide I band shifted to lower wave number significantly (P<0.01), while
      amide II band shifted to higher wave number(P<0.05), and the ratios of
      I1640/I1460 and I1640/I1550 were raised (P<0.01). The authors can conclude that
      the amounts and the secondary structure of protein in malignant tissue changed.
      (2) The peaks at 2955, 2920, 2870, 2850 and 1740 cm(-1) appeared less frequently
      suggesting that the relative quantity of lipid in malignant tissue decreased
      significantly; (3) Variation of bands related to nucleic acid: The band of 1241
      cm(-1) shifted to (1238.29+/-2.87)cm(-1), and the ratios of I1080/I1460 were
      raised significantly(P<0.05). The most possible reason for the changes was that
      the mutation of DNA and the amounts of nucleic acid had increased in malignant
      neoplasms. Experimental results show that the malignant thyroid tissues can be
      distinguished from the benign tissues by their infrared spectra. This approach
      proves that FTIR spectroscopy is a reliable and practicable method for thyroid
      cancer diagnosis in operations. The authors have expanded their research on
      detecting the thyroid cancer FTIR spectra via percutaneous and in vivo, and have
      achieved a positive result which is going to be reported in another paper.

PMID- 18330277
TI  - [Application of fourier transform infrared spectroscopy to non-invasive detection
      of pleomorphic adenoma of salivary gland in vivo].
AB  - In the present work, 20 patients with salivary pleomorphic adenoma were recruited
      for FTIR spectroscopic measurement. These obtained FTIR spectra were analyzed and
      compared. It was found that there were significant differences in the spectral
      features of the skin covering normal salivary gland, pleomorphic adenoma, and
      carcinoma change of pleomorphic adenoma, such as the changes in peak position,
      band shape and relative intensity of the bands in the ranges of 1000-1800 cm(-1)
      and 2800-3000 cm(-1). Pathological diagnosis demonstrated that 2 of the 20
      patients suffered actually carcinoma change of pleomorphic adenoma, which is in
      good agreement with the result of FTIR spectroscopicmeasurement. FTIR
      spectroscopic m ethodsuggested that pleomorphic adenoma is the intermediate
      between normal salivary gland and carcinoma change of pleomorphic adenoma.

PMID- 18330278
TI  - [The first and second cluster analysis of dual index grade sequence of IR
      fingerprint spectra of Guifudihuang pill and Jinkuishenqi pill samples and their
      quality evaluation].
AB  - In the present paper a method for identifying and evaluating traditional Chinese
      medicine (TCM) Jinkuishenqi pill and Guifudihuang pill samples is proposed.
      Mathematical statistics was applied to analyze the dual index sequences of
      infrared fingerprint spectra of components extracted from Jinkuishenqi pill and
      Guifudihuang pill samples with water, then the grade sequences were determined
      and the first and second clusters were performed based on these grade sequences.
      As a results, the most similar sample groups of different samples were also
      obtained. The Jinkuishenqi pill and Guifudihuang pill samples can be
      distinguished accurately with the most similar sample groups. The method put
      forward is new and effective to identify and evaluate combinational TCM
      quantitatively.

PMID- 18330279
TI  - [Recognition of plant parts of tobaccos based on infrared and near infrared
      spectra].
AB  - In the present paper, an IR/NIR spectrometry based on the pattern recognition
      using Mahalanobis distance method in the principal component analysis (PCA) space
      was established for the discrimination of plant parts of tobaccos. Effects of the
      type of IR/NIR spectrometers, calibration region of the spectra, model parameters
      and pretreatment of the spectra on the accuracy of discrimination were
      investigated using tobaccos cultivated in Yunan Province in 2003 and 2005 as case
      study. The recognition model shows the internal relationships between the
      information of spectra and the plant parts of tobaccos. The results indicate that
      both IR and NIR could be successfully used to recognize plant parts of the
      tobaccos, but the latter was better because it involves more sample information.
      It was found that the highest recognition accuracy, 94.11%, was obtained by using
      apparatus A with the second derivative spectra, while recognition accuracy of
      88.24% and 82.35% was respectively given by apparatus B with with the first
      derivative SNV spectra and IR spectrometer with first derivative spectra. For the
      same spectrometer, the optimal calibration region and principal component number
      were changed with samples and the spectral pretreatment method.

PMID- 18330280
TI  - [Preliminary study on identification of heroin from different route with
      clustering analysis by fourier transform infrared spectroscopy].
AB  - In the present paper, using Fourier transform infrared (FTIR) absorption
      spectrometry, the characteristic peaks of fingerprint infrared spectra of heroin
      samples from different routes were identified with clustering analysis
      successfully. It is a very fast, simple and reliable method. That is to say, a
      new method for the discrimination of heroin seizured from different routes is
      provided.

PMID- 18330281
TI  - [Study on quantitative analysis of cross linked copolymer by IR].
AB  - Cross linked copolymer silicon oil-Co-lactide (Si-co-LA) was analyzed
      quantitatively by IR. Potassium sulfocyanate (KSCN) was chosen as an inside mark
      material, because it has only one strong absorption peak at 2 100 cm(-1) and the
      peak was chosen as its quantitative peak. The peak at 1750 cm(-1) is the
      characteristic absorption of carbonyl and was chosen as thequantitative peak of
      lactide (LA). The ratio of the two absorbencies is I, and I=ALA/AKSCN. KSCN and
      LA were mixed according to a certain mass ratio C=MLA/MKSCN to prepare standard
      samples. The curve of C versus I is the quantitative work curve. The result of
      the experiment indicates that the work curve has good linearity in the range of
      2/5<MLA/MKSCN<8/5. The formulas calculating the proportion of every component in
      the cross linked copolymer were established: MKSC/MP=B, MLA/MKSCN=C, and (MLA/MP)
      x 100%=BC x 100%. Cross Linked Copolymer is hard to be analyzed quantitatively,
      because of its no dissolving and no melting. A convenient method of determining
      the component of the cross linked copolymer or other copolymer has been provided.

PMID- 18330282
TI  - [FTIR and XRD analysis of hydroxyapatite from fossil human and animal teeth in
      Jinsha Relict, Chengdu].
AB  - Diagenetic effect during burial on the hydroxyapatite in enamel and dentin from
      fossil human and animal teeth was examined, using X-ray diffraction (XRD) and
      Fourier transform infrared spectroscopy (FTIR). For the enamel and dentin of all
      fossil teeth, XRD patterns exhibit bulge line and overlap between major
      reflections of hydroxyapatite, and the crystallinity of hydroxyapatite is low.
      For each infrared spectrum, H2O and OH(-) have distinct peaks of absorbance, and
      PO4(3-) and CO3(2-) ions have intensive infrared vibration modes at the
      fundamental wave numbers. The component of hydroxyapatite of all fossil teeth is
      similar to the modern biological hydroxyapatite. Furthermore, the index (PCI)
      which reflects the hydroxyapatite crystallinity of each sample ranges from 2.4 to
      4.0 while the index (BPI) reflecting the amount of type B carbonate to phosphate
      indicates that the values of CO3(2-) content in hydroxyapatite are rather high,
      accordingly the crystallinity of all fossil hydroxyapatites are poor. It could be
      concluded that little alteration of hydroxyapatites from fossil human and animal
      teeth occurred in the process of diagenesis in Jinsha Relict, Chengdu, China.

PMID- 18330283
TI  - [Identification of Pericarpium Citrus Reticulatae from different regions using
      FTIR].
AB  - The essential oil of Pericarpium Citri Reticulatae from seven different regions
      were identified by Fourier transform infrared spectroscopy (FTIR) in the present
      paper. The result indicated that it's easy to find a fingerprint character of 2
      methyaminomethyester benzoic acid in the FTIR spectra of essential oil of the
      Pericarpium Citri Reticulataes collected from Guangdong and Guangxi, but it can't
      be seen in the FTIR spectra of th e samples from other regions, a nd especially,
      there is aobvious difference between Xinhui and non-Xinhui regions at 1690 and
      1644 cm(-1) in the FTIR spectra. Therefore, the simple, fast and accurate
      property of FTIR is a good foundation for the identification of Pericarpium Citri
      Reticulatae using its fingerprint character.

PMID- 18330284
TI  - [Study on the multicomponent quantitative analysis using near infrared
      spectroscopy based on building elman model].
AB  - The present paper introduces an application of near infrared spectroscopy (NIRS)
      multi-component quantitative analysis by building a kind of recurrent network
      (Elman) model. Elman prediction model for phenylalanine (Phe), lysine (Lys),
      tyrosine (Tyr) and cystine (Cys) in 45 feedstuff samples was established with
      good veracity. Twelve peak value data from 3 principal components straight
      forward compressed from the original data by PLS were taken as inputs of Elman,
      while 4 predictive targets as outputs. Forty seven nerve cells were taken as
      hidden nodes with the lowest error compared with taking 43 and 45 nerve cells.
      Its training iteration times was supposed to be 1000. Predictive correlation
      coefficients by the model are 0.960, 0.981, 0.979 and 0.952. The results show
      that Elman using in NIRS is a rapid, effective means for measuring Phe, Lys, Tyr
      and Cys in feedstuff powder, and can also be used in quantitative analysis of
      other samples.

PMID- 18330285
TI  - [Application of PCA-SVR to NIR prediction model for tobacco chemical
      composition].
AB  - Near infrared diffuse reflectance spectra of 50 tobacco samples were pretreated
      with PCA. The calibration models of determination of the main components in
      tobacco were developed with support v ector regression (SVR). The models
      weretested with leave-one-out (LOOCV) method and optimized with parameters of
      kernel function, penalty coefficient C and insensitive loss function. The root
      mean square errors (RMSE) with leave-one-out cross validation of the optimal
      models of nicotine, and total sugars, reductive sugar, and total nitrogen were
      0.313, 1.581, 1.412 and 0.117 respectively. Based on the comparison of RMSE of
      the SVM model with those of the partial least square (PLS), multiplicative linear
      regression (MLR) and back propagation artificial neuron network (BP-ANN) models,
      it was found that the SVR model was the most robust one. This study suggested
      that it is feasible to rapidly determine the main components concentrations by
      near infrared spectroscopy method based on SVR.

PMID- 18330286
TI  - [High temperature Raman spectroscopy techniques and its applications].
AB  - Based on the frequency and time domain characters of heat radiation, high
      temperature Raman spectroscopy techniques were aralyzed and summarized. Thereby,
      two high temperature Raman systems were set up. One is an accumulated time
      resolved macro-Raman spectroscopy system, and the other is an accumulated time
      resolved and confocal coupled micro-Raman spectroscopy system. Finally, their
      applications in the study of high temperature processes such as melt structure
      and phase transformation, crystallization as well as samples with high
      fluorescence were intrtoduced.

PMID- 18330287
TI  - [Raman spectra of fossil dinosaurs from different regions].
AB  - Raman microscopic spectra in the higher wave number region were obtained from 7
      fossil dinosaurs specimens from different regions. The specimens of fossil
      dinosaurs are different parts of bone. The Raman spectra of fossil dinosaurs
      indicate the high similarity among peak positions of different fossil dinosaurs;
      but important differences exist in the spectral peak figures. In the wave number
      region of 1000-1800 cm(-1) the Raman spectra of the same bone part fossils from
      different regions are very similar, example similarities between spectra of
      Lufeing backbone head and Yua nmou backbone head; Lufeng limb bone and Wuding
      limb bone. There are relations between the same bone part spectra of different
      fossil dinosaurs. The characteristic does not relate to regions. Raman spectra of
      fossil dinosaurs cannot be used to distinguish fossil source, although the part
      of bone can be used as an indicator to narrow the range of possible geographical
      origins.

PMID- 18330288
TI  - [Raman scattering studies on 0.5PZN-0.5PZT piezoceramics].
AB  - PZT based multi-system has shown super piezoelectric properties when the
      composition was located at morphotropic phase boundary (MPB), which divided the
      regions into rhombohedral and tetragonal structures equally. In the present
      paper, the diffuse phase transition and phase coexistence of rhombohedral and
      tetragonal phases of 0.5PZN-0.5PZT ceramics were investigated by Raman scattering
      spectroscopy in detail. The results revealed that compared with pure PZT, the
      width of Raman bands of 0.5PZN-0.5PZT was quite broad, indicating that the system
      has strong relaxor feature. According to the temperature dependence of dielectric
      permittivity, the indicator of degree of diffuseness, gamma, was calculated and
      the values were as high as 1.71. Through the separation by Gauss fitting of the
      Raman bands, the intensities of different Raman vibration modes, such as the
      tetragonal E (3TO), A1 (3TO), E (4LO) and A1 (3LO) modes, as well as the
      rhombohedral R1 and Rh modes, were determined. The results indicated that for
      0.5PZN-0.5PZT system, the fraction of rhombohedral phase was equal to the
      tetragonal phase, which has also been affirmed by XRD results and suggested that
      the system was close to the MPB. Excellentpiezoelectric properties, such as kp
      (0.66) and d33 (425 pC/N), were found in 0.5PZN-0.5PZT system, showing a great
      promise of this system as practical materials for piezoelectric actuators.

PMID- 18330289
TI  - [Using hyperspectral derivative index to monitor winter wheat disease].
AB  - The canopy reflectance of winter wheat that infected different severity stripe
      rust was measured through artificial inoculation, the disease index (DI) of the
      wheat corresponding to the spectra was acquired in the field, and the parameters
      of biochemistry and biophysics were measured indoors. The 1st derivatives were
      analyzed. The results show that the 1st derivative values increase at the green
      edge (500-560 nm), while decrease at the red edge (680-760 nm) with DI
      increasing. The ratio of the sum of derivatives within the red edge (SDr') to the
      sum of derivatives within the green edge (SDg') has a higher negative linear
      correlation with DI, with a coefficient of determination r2=0.9210 (n=28), and
      that can be use to identify the healthy and disease crops 12 days before symptoms
      appearing. Therefore, the derivative vegetation index SDr/SDg can be used to
      monitor crops disease information. The conclusion is significant and may find
      application in acquiring crops disease information using hyperspectral remote
      sensing, and has a important meaning for increasing yields of crops and ensuring
      security of food supplies.

PMID- 18330290
TI  - [Study on the spectrum of the flocculent conformation of polymer ferric sulfate
      flocculants].
AB  - In the present paper, the flocculent conformation and qualities of polymer ferric
      sulfate flocculants were studied by the ultraviolet-visible spectrum. The spectra
      of polymer ferric sulfate flocculants at different pH values, the microcosmic
      flocculent conformation of polymer ferric sulfate flocculants corresponding to
      some peaks in the spectrum, the reaction mechanism and the effects of different
      pH value on turbidity and colour removal and described. The absorbance of peaks
      in the wavelength range of 200-1100 nm all increased with pH value rising from
      1.0 to 2.5. The absorbance of peaks in the wavelength range mentioned above did
      not continuously increased with pH value rising above 2.5, and some of them are
      even decreased apparently. The flocculent effects of turbidity and colour removal
      on stimulant waste water is optimum at pH 2.0. When pH value is in the range of
      1.5 to 2.0 and 2.0 to 2.3, the flocculent effects are also better. However, the
      flocculent effect is decreased apparently when pH value is over 2.5. The change
      in the spectral curve of the different pH polymer ferric sulfate flocculants is
      corresponding to the flocculent effects of turbidity and colour removal on
      stimulant waste water to some extent. The research method has potential
      application prospect for the better flocculation conformation analysis and
      identification of the polymer ferric flocculants. And it can provide some easy
      and actable methods for the flocculation conformation analysis and identification
      of high polymer ferric flocculants.

PMID- 18330291
TI  - [Spectroscopy study on the interaction of colchicine and human serum albumin].
AB  - The binding reaction of colchicine with human serum albumin (HSA) was studied by
      UV-Vis absorption, fluorescence and circular dichroism spectrometry. The results
      indicated that colchicine led to the increase in UV absorption and the quenching
      of intrinsic fluorescence of HSA. As the temperature increased, the quenching
      constant Ksv decreased. The binding constants and the numbers of the binding
      sites of the interaction between colchicine and HSA at different temperatures
      were obtained. The thermodynamic parameters, enthalpy change (DeltaH) and entropy
      change (DeltaS), were calculated to be -11.66 kJ x mol(-1) and 51.507 J(mol x K)(
      1) respectively according to Van't Hoff equation, which suggested that the main
      binding force between colchicine and HSA was static interaction. The protein
      conformation was altered (CD date) with decreasing of alpha-helices in the
      presence of colchicine. The results showed that the quenching mechanism of the
      combination of colchicine with human serum albumin was a static quenching
      procedure.

PMID- 18330292
TI  - [Spectrometric study on the interaction of doxepin hydrochloride and fast green
      and its application].
AB  - The characteristics of resonance light scattering and absorption spectra of
      doxepin hydrochloride with fast green were investigated, and a new analytical
      method for doxepin hydrochloride was described. In the buffer solution of pH 4.0,
      doxepin hydrochloride can strengthen the signal of resonance light scattering of
      fast green. The effective factors, including the order of addition of the
      reagents, acidity and kinds of the buffers, and concentration of fast green were
      investigated. Under the optimum conditions, the scattering peaks of the system
      are at 344 and 486 nm, while the maximum is at 344 nm. The enhanced intensity of
      RLS is proportional to the concentration of doxepin hydrochloried in the range of
      8.75 x 10(-3)-4.88 x 10(-2) mg x mL(-1). The detection limit for doxepin
      hydrochloried is 1.72 x 10(-5) mg x mL(-1). The relative standard deviation
      obtained from eleven determinations for a 0.025 mg x mL(-1) standard solution of
      doxepin hydrochloried is 1.4%. The method was applied to the determination of
      doxepin hydrochloric in pharmaceutical preparations. The results were compared
      with those obtained by the reference method, and t-test showed no significant
      difference between the two methods.

PMID- 18330293
TI  - [Study of LCD tricolor spectrum characteristic].
AB  - The electro-optical characteristic of TB3639 liquid crystal light valve under
      both voltage-drive and frequency-drive modes was measured using
      spectrophotometer, and the change in tricolor transmissivity with the two methods
      was analyzed. The result shows that the changes in tricolor transmissivity with
      these two methods are not identical, and color cast will appear, which will
      influence display quality. The change in tricolor transmissivity becomes more
      obvious with the changes in voltage in voltage-drive mode, in which the maximum
      difference is 11% and the minimum is 0. The change in tricolor transmissivity has
      better uniformity in frequency-drive mode and the difference of transmissivity is
      relatively small with the maximum difference of 4% and the minimum of 2.5. The
      color should be adjusted and compensated in order to get exact hue and color
      saturation, and this will help to study further for improving the performance of
      liquid crystal display.

PMID- 18330294
TI  - [Study on the interaction between fangchinoline and bovine serum albumin].
AB  - The binding reaction of fangchinoline with bovine serum albumin was studied at
      different temperatures by fluorescence quenching spectra, synchronous
      fluorescence spectra and ultra-violet spectra. It was shown that fangchinoline
      has a strong ability of quenching the fluorescence of BSA. The Stern-Volmer curve
      of the fluorescence quenching of BSA by fangchinoline indicated that the
      quenching mechanism of fangchinoline to BSA was a static quenching. According to
      the Forster theory of non-radiation energy transfer, the binding distances (r) at
      different temperature were 2.51 nm (27 degrees C), 2.72 nm (37 degrees C) and
      2.89 nm (47 degrees C), respectively, while the binding constants (KA) were 1.05
      x 10(5) L x mol(-1) (27 degrees C), 3.31x 10(5) L x mol(-1) (37 degrees C), and
      7.24 x 10(5) L x mol(-1) (47 degrees C), respectively. The thermodynamic
      parameters showed that the interaction of fangchinoline and BSA was mainly driven
      by hydrophobic force. Synchronous spectrum was used to investigate the
      conformational changes of BSA.

PMID- 18330295
TI  - [Preparation and study on the spectra of conductive nano-silver film].
AB  - The preparation and study on the spectra of conductive nano-silver film were done
      under mild conditions. The silver citrate emulsion coating on the surface of PET
      was reduced by ascorbic acid (Vc) aqueous solution to prepare a silver film. The
      morphology, crystal structure, surface roughness and conductivity of the silver
      film were measured by FTIR, UV-Vis spectrum, X-ray diffraction (XRD), scanning
      electron microscope, scanning probe microscope system and so on. It was found
      that the silver citrate emumsion has a homogenous particle distribution from 60
      nm-150 nm. The UV-Vis spectrum of the silver film shows a peak at 430 nm, and the
      silver thin film was considered to have a typical nano-scale structure. By the
      comparison of the XRD patterns of the films treated and untreated with water, it
      was concluded that the further deoxidization of silver citrate could be
      accelerated by water. The crystal structure of the silver film was improved and
      the surface resistance of the silver film was decreased greatly. The effect of
      ethanol on the decrease in the resistance of the silver film is much less than
      that of water.

PMID- 18330296
TI  - [Spectral diagnosis of hydroxyl radical in multiphase pulsed discharge system].
AB  - A gas-liquid hybrid pulsed discharge system with a multi-needle-to-plate
      electrode geometry was used in the present study. A multiphase (gas-liquid-solid)
      pulsed discharge system was then formed by adding glasses beads immobilized with
      TiO2 photocatalyst into the discharge system. In the present paper, ultraviolet
      light produced during the pulsed discharge process was used as the lamp-house to
      induce the photocatalytic activity of the TiO2 photocatalyst. The synergistic
      effect of pulsed discharge and TiO2 photocatalysis was reviewed by the spectral
      diagnosis of hydroxyl radical ( *OH) in the pulsed discharge system. The obtained
      results showed that the emission spectrum of *OH could be observed at 306 nm
      (A2Sigma+-->X2II), 309 mn (A2Sigma+ (v' = 0) --> X2II (v" = 0)) and 313 nm
      (A2Sigma+ (v' = 1) --> X2II (v" = 1) transition). The relative emission intensity
      of *OH at 313 nm in the discharge system was the strongest among the three
      characteristic spectra. The relative emission intensity of *OH at 313 nm was
      stronger by adding TiO2 photocatalyst into the pulsed discharge system than that
      in the sole pulsed discharge system. In the case of experiments that changing the
      gas bubbling varieties and initial solution pH values, the results revealed that
      the relative emission intensity of *OH at 313 nm in the synergistic system was
      stronger when Ar was used as bubbling gas compared with that when air and oxygen
      were bubbled into the reaction system. Furthermore, the acidic solution system
      was favorable for producing more *OH, and therefore the corresponding emission
      intensity of *OH at 313 nm was stronger than that in the neutral and basic
      solution.

PMID- 18330297
TI  - [Study on photocatalytic decomposition of azo-dyes by ZnO/carbon nanotubes
      composites by UV-Vis spectroscopy].
AB  - ZnO/carbon nanotubes composites were prepared by hydrothermal treatment of the
      mixture of zinc nitrate and acid-treated multiwalled carbon nanotubes and
      characterized by transmission electron microscope (TEM) and X-ray powder
      diffraction (XRD). The TEM image indicated that ZnO nanoparticles with a diameter
      about 28 nm covered the carbon nanotubes. The XRD pattern shows that ZnO
      nanoparticles attached to the MWNTs exhibit a hexagonal phase. The diffraction
      peaks can be assigned to (100), (002), (101), (102), (110), (103), (200), (112)
      and (201) planes of the crystalline ZnO, respectively. The average size of the
      crystalline ZnO, calculated from the half-width of the (100) diffraction peak by
      the Scherrer equation, is 27.8 nm, which accords with the TEM observation. The
      ZnO/carbon nanotubes composites were used as a photocatalyst under sunlight for
      the decomposition of azo-dye, which was studied by UV-Vis spectroscopy. The
      effects of the illumination time, catalyst amount, initial dye concentration and
      the different structures of the dye on the photocatalytic process were
      investigated. It was noted that the intensity of the absorption peak
      corresponding to the azo-dye decreased rapidly at 400 nm during the photolysis
      process and the decomposition of azo-dye was a quasi-first order reaction. The
      decomposition rates for azo-dyes such as acid orange, Acid bright red, Acid light
      yellow are 0.09, 0.28 and 0.22 mg x L(-1) x min(-1), respectively, which maybe
      resulted from their different functional groups. It can be stated that the
      complete removal of color, after selection of optimum operation parameters, can
      be achieved in relatively short time by using ZnO/carbon nanotubes composites.
      After recycling 5 times, the catalyst still has more than 50% efficiency.

PMID- 18330298
TI  - [Comparative research on determination of water integrated organic pollution
      index with three dimensional excitation-emission fluorescence spectroscopy and
      traditional wet chemical methods].
AB  - Three dimensional excitation-emission fluorescence spectra, chemical oxygen
      demanding (COD) and dissolved organic carbon (DOC) for water samples from Science
      Island, Chaohu Lake and Taihu Lake were determined. The COD values of the samples
      from Chaohu Lake were linearly correlated with the DOC values. Relationships of
      dissolved organic matter (DOM) concentrations determined by three dimensional
      excitation-emission fluorescence matrix (3DEEM), observed protein-like
      fluorescence intensity (Ipro-like) and humic-like fluorescence intensity (Ihum
      like) to the chemical oxygen Demanding (COD) for all the samples from different
      sources were analyzed. Results indicated that DOM concentrations measured by
      3DEEM and COD for the water samples from Science Island were well linearly
      related (r = 0.82172), and the linear relationships also existed between Ipro
      like. and COD (r = 0.84651), as well as Ihum-like and COD (r = 0.83689). However,
      for the water samples from Chaohu Lake and Taihu Lake, no linear relationships
      existed. The cause of the above difference between the water samples from Science
      Island and those from Chaohu Lake and Taihu Lake, and the feasibility and the
      limits of the integrated organic pollution measurement using three dimensional
      excitation-emission fluorescence spectroscopy were further discussed.

PMID- 18330299
TI  - [Study of derivatives of 2, 6-diaminopyridine as fluorescence probe of transition
      metal ions].
AB  - Three derivatives of 2, 6-diaminopyridine were synthesized with naphthyridine
      ring and -NH2, -OH and -NHCOCHCH2 groups. They are 2, 4-dimethyl-7-hydroxyl-1, 8
      naphthyridine (DMHND), 2, 4-Dimethyl-7-amino-1, 8-naphthyridine (DMAND) and
      DMAAN. The binding ability of the derivatives of 2, 6-diaminopyridine for metal
      ions in acetonitrile was investigated using UV-Vis and fluorescence spectrometry.
      The changes of the dyes spectra were observed in the presence of transition metal
      ions, but were not observed in the presence of K+ , Na+ , Mg2+ , Ca2+ and Pd2+.
      Except for DMHND that has weak binding ability for Cu2+, two dyes can bind with
      Cu2+ at the ratios of DMAAN : Cu2+ = 1 : 1, DMAND : Cu2+ = 1 : 1. The resulting
      binding curves were analyzed by nonlinear regression methods, giving the
      association constant for DMAAN to be about 4.4 x 10(5) L x mol(-1), and about 6.3
      x 10(6) L x mol(-1) for DMAND. DMAND contains an electron-donating group (amino
      group) conjugated to an electron-withdrawing group (the pyridine ring), and
      undergoes intramolecular charge transfer from the donor to the acceptor upon
      excitation by light. When Cu2+ interacting with the N of the pyridine ring
      enhances the electron-withdrawing character of this group, the spectrum is thus
      red-shifted and the intensity is increased. DMAND displayed a high sensitivity
      among the three derivatives of 2, 6-diaminopyridine as the fluorescence probe of
      transition metal ions.

PMID- 18330300
TI  - [The analysis of sinusoidal modulated method used for measuring fluorescence
      lifetime].
AB  - This paper has built a system with a sinusoidal modulated LED as the excitation
      source. Such exciter was used upon the sample Eu2 L'3 x nH2O (L' = C4H4O4). Both
      the excitation light and the 5Do-7F2 emission of Eu3+ ion were measured.
      Fluorescence lifetime, which approximate to 0.680 ms, can then be obtained from
      the measured excitation and fluorescence waveforms by non-linear least square
      curve fitting based on the principle of phase-shift measurement of fluorescence
      lifetime. Data processing methods considering respectively the high order
      harmonics in the modulation and multi-exponential decay of the fluorescence were
      discussed. A method of utilizing Fourier series expandedness to amendatory the
      result was put forward. Accordingly, the applicability for phase-shift method was
      expanded as well as a more exact result was acquired.

PMID- 18330301
TI  - [Enhancement effect on fluorescence of Tm3+ mixed dysprosium perchlorate in
      phenyl-phenacyl sulfoxide].
AB  - Nine different proportional complexes of different nuclear rare earth perchlorate
      (Dy3+ and Tm3+ are mixed) with phenyl-phenacyl sulfoxide (L= C6H5COCH2SOC6H5)
      have been synthesized and characterized. Element analysis and coordination
      titration studies suggest that the complexes have the composition of (DyxTmy) L5
      (ClO4)3 x 2H2O (x : y = 1.000 : 0.000, 0.999 : 0.001, 0.995 : 0.005, 0.990 :
      0.010, 0.900 : 0.100, 0.800 : 0.200, 0.700 : 0.300, 0.600 : 0.400, 0.500 :
      0.500). IR studies indicate that the ligand is bonded with RE (III) through one
      oxygen atom in sulfoxyl group, and the oxygen atom in carbonyl group did not
      bond. The molar conductivities measured in the DMF solution indicate that three
      inorganic anions ClO4(-) are non-coordinated. The fluorescence emission intensity
      of Dy3+ complexes would be enhanced strongly by mixing Tm3+. Tm3+ has the best
      sensitization to the fluorescence of Dy3+ in the ratio of 0.990 : 0.010. The
      fluorescence intensity can be increased to 246%.

PMID- 18330302
TI  - [Effect of glucose concentration in human serum on fluorescence intensity].
AB  - Blood plays an important role in the clinical diagnosis and treatment; many
      diseases may lead to changes in the blood composition or characteristic
      properties. Therefore, the analysis of blood sugar will be of great importance.
      The present paper studies the difference of fluorescence intensity stimulated by
      light wave between normal blood serum and hyperglycemia blood serum. The result
      shows that the average grey level of fluorescence image at 365 nm increases
      obviously with the changes in the concentration of glucose; however, the average
      grey changes little at 353, 369 and 405 nm. This shows that the main effect of
      serum glucose on the fluorescence intensity peak appears at 365 nm. Because the
      fluorescence intensity has something to do with the concentration of the
      fluorescence material, the blood glucose concentration influences directly the
      fluorescence intensity at 365 nm. Therefore, it is possible to judge blood sugar
      content, and to make sure whether the content exceeds the normal value or not by
      comparing the fluorescence intensity of the blood serum measured at 365 nm. This
      technique of optical measurement provides an experimental basis for the diagnosis
      of blood diseases.

PMID- 18330303
TI  - [Nanosilver sensitized fluorescence and second-order scattering of Tb (III)
      norfloxacin and its application].
AB  - Norfloxacin (NFLX) can form complex with Tb(III) ion, and the intramolecular
      energy transfer from NFLX to Tb (III) takes place when excited. And thus the
      characteristic fluorescence of Tb (III) ion is enhanced and the maximum
      fluorescence peak locates at 545 nm. The second-order scattering (SOS) peak at
      545 nm also appears for the Tb (III)-NFLX complex with the excitation wavelength
      of 272 rnm. When the silver nanoparticles were added to the Tb (III)-NFLX binary
      system, the luminescence intensity at 545 nm greatly increased. And the relative
      intensity is proportional to the amount of NFLX. Based on this phenomenon, a
      novel method for the determination of NFLX has been developed by using a common
      spectrofluorometer to measure the intensity of fluorescence and SOS. The
      calibration graphs for NFLX are linear in the range of 6.0 x 10(-9)-1.0 x 10(-5)
      mol x L(-1), and the detection limit is 4.4 x 10(-9) x mol x L(-1). This method
      was applied satisfactorily to the determination o f NFLX in capsule and eye drop
      samples. The experimental results showed that it is the certain size and certain
      concentration of silver nanoparticles that can greatly enhance the fluorescence
      SOS intensity.

PMID- 18330304
TI  - [Fluorescence and visible spectroscopic studies on interaction of beta
      cyclodextrin-thionine inclusion complex with DNA].
AB  - The inclusion of beta-cyclodextrin (CD) for thionine (TH) and the interaction of
      DNA with CD-TH inclusion complex were investigated by fluorescence and visible
      absorption spectrometry. TH with beta-CD formed a 1 : 1 inclusion complex with
      the stability constant of 527 L x mol(-1) (visible spectrometry)/444 L x mol(-1)
      (fluorescence) in the pH 7.2 PBS buffer solutions. The addition of DNA makes the
      absorbance of the inclusion complex decrease and the absorption spectrum shift
      toward long wavelengths. The fluorescence experiments indicated that the presence
      of DNA makes the emission peak of CD-TH shift toward short wavelengths and the
      fluorescence of inclusion complex quench, and the quenching constant was
      calculated to be 6.12 x 10(4) L x mol(-1) by Stern-Volmer method. All the data
      confirmed that CD-TH reacted with DNA in intercalative mode, and the binding
      numbers and the binding constant were estimated to be 1 and 3.47 X 10(4) L x mol(
      1) by spectrophotometry.

PMID- 18330305
TI  - [Study on the binding reaction features between naphthol green B and bovine serum
      albumin by fluorescence spectrophotometry].
AB  - At different temperatures, the binding of naphthol green B (NGB) to bovine serum
      albumin (BSA) was studied by the fluorescence spectroscopy, three-dimensional
      fluorescence spectrum, synchronous fluorescence spectrum and ultra-violet
      spectrum. It was shown that this compound has a quite strong ability to quench
      the fluorescence from BSA. After analyzing the fluorescence quenching data
      according to Sterm-Volmer equation and Lineweaver-Burk equation, it was found
      that BSA had reacted with naphthol green B and formed a new compound, the
      quenching action was due to static fluorescence quenching, and the action force
      was electrostatic interaction. According to the Lineweaver-Burk equation and
      thermodynamic equation, the average value of the binding constant (KLe: 1.411 x
      10(5) L x mol(-1)), the thermodynamic parameters (DeltaHtheta: -5.707 kJ x mol(
      1), DeltaGtheta: -30.25 kJ x mol(-1) and DeltaStheta: 79.95 J x K(-1)) and the
      amounts of binding sites (1.258) were obtained, providing important information
      for the research on the configuration modification of BSA because of the added
      naphthol green B, biological effects in a living body, and the coloration
      mechanism of naphthol green B.

PMID- 18330306
TI  - [Determination of terbium (III) with EHPG-Tb (III) system by fluorescence
      spectroscopy].
AB  - The fluorescence of terbium was sensitized after addition of terbium to the
      ethylene-N, N'-bis (o-hydioxyphenylglycine) (EHPG) solution. A novel and simple
      method used for the determination of Tb (III) was developed by means of
      fluorescence spectroscopy in the presence of EHPG. It was showed that the
      relative fluorescence intensity is proportional to the concentration of terbium
      ions, while the molar ratio of terbium to EHPG is less than 1.0 in the system.
      The maximum wavelengths of excitation and emission are 295 and 547 nm
      respectively. The optimal range of pH is 7-9. The linear range of detection of
      the concentration of terbium is from 1.0 x 10(-8) mol x L(-1) to 1.0 x 10(-5) mol
      x L(-1), with a detection limit of 1.18 x 10(-9) mol x L(-1). The relative
      standard deviation is still within +/-3% in the presence of other lanthanide
      ions. The method was applied to the determination of the recoveries of synthetic
      samples and a rare earth sample with satisfactory results.

PMID- 18330307
TI  - [Study on the interaction between Fe3(CO)12 and DNA by electronic and
      fluorescence spectrophotometry].
AB  - The interaction between Fe3(CO)12 and DNA was investigated by absorption and
      spectra, fluorescence spectra. The absorption of EB-DNA system in the presence of
      Fe3 (CO)12 showed that Fe3(CO)12 could partly sustain the place of EB. The result
      of fluorescence spectra suggested that Fe3(CO)12 could enhance the fluorescence
      intensity of DNA sharply. All the experimental results indicated that the
      intercalative binding mode was the major model for the interaction of Fe3(CO)12
      cluster complex with DNA.

PMID- 18330308
TI  - [Fluorescence spectrum analysis system for protoporphyrin IX in serum based on
      wavelet transform].
AB  - Protoporphyrin IX is an important kind of organic compound for vital movement,
      and can be used as the sign of tumour blood. Human protoporphyrin IX content in
      serum is very low, and affected by various factors. The serum fluorescence
      spectrum analysis system based on wavelet transform was used to discriminated the
      protoporphyrin IX weak signals. The protoporphyrin IX fluorescence spectrum was
      obtained by a multi-function spectrum measuring system, and decomposed several
      times by wavelet transform to distinguish the noise and spectrum signals. The
      fluorescence spectrum can be divided into corresponding discrete approximations
      signals (a1-a6) and discrete details signals (d1-d6) by six times of
      decomposition, showing the signal frequency decreasing with decomposition times
      increasing and the protoporphyrin IX fluorescence character peak appears here.
      The weak signals were discriminated and the exactly component and quantity can be
      acquired for further analysis. So it can be analysed quantitatively. The
      researches in the present paper provide the potential application in the
      diagnosis of incipient tumous using the serum fluorescence spectrum

PMID- 18330309
TI  - [Fluorescence spectra analysis of papain treated by pulsed electric field].
AB  - Tryptophane, tyrosine and phenylalanine are there kinds of fluorescent amino
      acids and exist in papain, so the structure change of papain can be measured by
      fluorescence spectra analysis without exterior fluorescence probe. Fluorescence
      excitation spectrum, emission spectrum and polarization spectrum were used to
      analyze the possible mechanisms of papain's activity change after being treated
      by pulsed electric field (PEF). Results demonstrated that the relative activity
      of papain was decreased by 56.5% after PEF treatment under the condition of
      electric field strength 50 kV x cm(-1), frequency 1500 Hz, pulse width 40 micros
      and pulse number 19,800. The spectra of fluorescence excitation showed that the
      relative fluorescence strength of the treated sample was distinctly higher than
      the untreated one, even at peak position (280 nm) which was 80 and 120 for
      untreated and treated samples, respectively. The peak position in the
      fluorescence emission spectrum of treated sample was shifted from the original
      342 nm to about 346 nm, and its fluorescence polarization degree was much smaller
      compared to the untreated sample. These phenomena indicated that the alpha-helix
      structure of papain was loosened or broken down after being treated by PEF. This
      treatment made the amino acid's residue exposed from inside to outside, and even
      some fluorescent amino acids such as tryptophane, tyrosine and phenylalanine were
      decomposed from the alpha-helix structure of protein and went into the solution
      which helped increase the fluorescent strength. This effect led to the active
      site change of the enzyme and finally inactivated it.

PMID- 18330310
TI  - [New iron-porphyrin/vanadium-substituted polyoxometalate catalyst: synthesis,
      characterization and catalytic activity].
AB  - A new kind of iron-porphyrin/vanadium-substituted polyoxometalate coordination
      compound was synthesized by the ion exchange reaction of FeTTMAPPI and
      H5PMo10V2o40 in solution. The new catalyst was characterized by IR spectrometry
      and UV-Vis spectrometry. As an excellent catalyst, its effects on benzene
      hydroxylation and catalytic capabilities were studied with H2O2 solution as the
      oxidant. The results indicated that the products contained the conjugated
      structure of porphyrin and the cage structure of polyoxometalate, the V atom in
      polyoxometalate is the main centre of catalytic activity, meanwhile the presence
      of iron-porphyrin could increase its catalytic activity greatly.

PMID- 18330311
TI  - [Synthesis and spectroscopic properties of tetra-(dimethylaminophenyl) porphyrin
      and its metal complexes].
AB  - Porphyrin and metalloporphyrin distribute widely in nature and they play an
      important role in the life. Synthesis of porphyrin compounds with special
      function has been the focus of attention. In the present paper, porphyrin and
      metalloporphyrin compound were synthesized by the following method: by one-step
      synthesis, tetra-(dimethylaminophenyl) porphyrin (T(DMAP) P) was synthesized with
      propionic acid, acetic acid and nitrobenzene as solvent and 4
      dimethylaminobenzaldehyde and pyrrole as raw material. The yield was 24.24%. The
      complexes of T(DMAP)P with Zn2+, Mn2+ and Tb3+ were synthesized by solvent of
      chloroform-N, N dimethylformamide (1 : 1). The effects of solvent, temperature
      and reaction time on the reaction were discussed. Optimum proportion between
      porphyrin and metallic salts was studied also and the molar ratios of T(DMAP)P to
      Zn (CH3COO)2 x 2H2O, T(DMAP)P to MnCl2 x 4H2O, and T(DMAP)P to TbCl3 were 1 :
      1.2, 1 : 1.4, 1 : 1.5, respectively. The synthesis of metalloporphyrins under
      mild conditions is simper with high yield (94.2%, 91.7% and 90.5% for T(DMAP) P
      combined with Zn2+ , Mn2+ and Tb3+ respectively) and the unstability of
      metalloporphyrin could be avoided. The constitution and structures of these
      compounds were studied by elemental analyses, infrared spectrum (IR), and
      ultraviolet-visible spectrum (UV-Vis). The conductivity of porphyrin compound
      with different concentration and temperature was studied. It was found that the
      molar conductivity of T(DMAP)P-TbCl(74.6 s x cm(-2) mol(-1)) was greater than
      that of T(DMAP)P-Zn (8. 8 s x cm(-2) x mol(-1)) and T(DMAP)P-Mn (25.8 s X cm(-2)
      mol(-1)). So T(DMAP) P-TbCl could be regarded as the 1 : 1 electrolyte compound
      while T(DMAP)P-Zn and T(DMAP)P-Mn were non-electrolyte compounds. The influences
      of different metal ions on the reaction were investigated. The discussion was
      concentrated on the molecular spectra of porphyrin and metalloporphyrin. Compared
      with tetraphenyl porphyrin, the absorption of T(DMAP) P and its metal complexes
      had red-shifts due to the substituent groups and metal ions. When the porphyrin
      rings were occupied by metal ions, the number of Q band decreased and the
      absorption peak intensity decreased. Among these metalloporphyrin compounds, the
      maximum absorption of T(DMAP)P-TbCl had the biggest red-shifts and could be used
      as ideal photosensitizer.

PMID- 18330312
TI  - [Determination of Sb and Bi in 24 international geological reference materials by
      using pressurized acid digestion-ICP-MS].
AB  - The authors studied in detail the memory effect of Bi, Sb, As and Te in ICP-MS.
      The produced memory effects of these element were in the order of Bi>Sb>Te>As. Bi
      was seriously adsorbed by the polypropylene sample storing bottle and the sample
      introduction system in the low nitric acid medium (0.01%-1% HNO3). The washout
      effect of 0.1% HF was found to be better than those of 6% HNO3 and 0.1% HClO4.
      Under the given experiment conditions, the instrumental limit of detection was
      0.001 and 0.0001 ng x mL(-1) for Sb and Bi, respectively. The authors report the
      determination of Sb and Bi in 24 international geological reference materials by
      using pressurized acid digestion-ICP-MS (including AGV-2, BHVO-2, BCR-2, etc.).
      Most of the results were found to be in reasonable agreement with the reported
      values in the literature. The authors' determined values of Sb for GSR-1
      (granite; 0.30 microg x g(-1)) and JP-1 (peridotite; 0.045 microg x g(-1)) are
      obviously higher than those reported values. This is attributed to the efficient
      pressurized acid digestion, which is generally much more efficient than
      conventional wet digestions for insoluble minerals.

PMID- 18330313
TI  - [Effects of soil on the concentration of rare earth in Nanfeng orange].
AB  - Nanfeng orange is a famous fruit in the world, but the content of rare earth in
      the fruit and its relation to the content in soil were little studied. The
      present paper studied the contents of rare earth in Nanfeng orange fruit and the
      effects of soil planting Nanfeng orange on the contents of rare earth in Nanfeng
      orange fruit by ICP-MS/ICP-AES in order to find the relation of rare earth
      content in the soil to that in Nanfeng orange fruit. The results showed that ten
      kinds of rare earths were detected, namely La, Ce, Pr, Nd, Sm, Eu, Gd, Dy, Ho and
      Yb, whose contents range from 0.63 to 0.01 ng x g(-1), while the contents of the
      ten elements range from 29.36 to 0.07 microg x g(-1) in the soil All data showed
      that the content of rare earth in fruits is right relative to that in soil. So
      the authors can conclude that fertilizing with rare earth should be the best way
      to enhance the content of rare earth in Nanfeng orange fruits.

PMID- 18330314
TI  - [Determination of W, Mo and other 8 elements in powder metallurgical materials by
      ICP-AES].
AB  - Samples were dissolved using nitric acid, perchloride acid and hydrofluoride acid
      in the medium of 0.025 mol x L(-1) EDTA with a kind of standard solutions, and
      the element contents of Ni, Cu, V, Mn, W, Mo, Co and Cr were determined by ICP
      AES method. After investigating the spectral interfere from matrix element and
      coexistent elements, optimum spectral lines were selected for each analyzed
      element, and the analytical precision, detection limits and recoveries were
      measured. The results show that the detection limits of the method are very low,
      relative standard deviations (n=10) are less than 1%, and the recoveries range
      from 98.2% to 101.6%. The proposed method is accurate, reliable, simple, and
      rapid. The method satisfies.

PMID- 18330315
TI  - [Determination of Cd in sediment samples by flow injection on-line anion exchange
      combined with vapour generation-atomic fluorescence spectrometry].
AB  - In the present work, a method was developed for the determination of ultra-trace
      levels of Cd in sediment samples by atomic fluorescence spectrometry (AFS). A
      flow injection on-line separation and preconcentration technique coupled with an
      intermittent injection vapor generation technique was employed in the study. The
      instrument operating parameters and chemical conditions were optimized. In a 2.0
      mol x L(-1) HCl solution, Cd (II) was adsorbed on 717-strong alkaline anion
      exchange resin, while Cu (II) and Pb (II) passed throngh. Then Cd (II) was eluted
      by 0.5 mol x L(-1) HNO3. The eluting solution was determined directly by
      intermittent injection vapor generation atomic fluorescence spectrometry. It was
      showed that Cd (II) can be preconcentrated effectively and the interference can
      be completely eliminated by this improved method. The Cd atomic vapor generation
      efficiency could be greatly enhanced in the presence of Co (II) and 1, 10
      phenanthroline. The linear range of the determination was 0-12 microg x L(-1)
      with a detection limit of 0.058 microg x L(-1). The RSD (5 microg x L(-1), n=7)
      was 1.09%. The method was convenient, rapid and successfully validated by using
      national water sediment standard reference materials.

PMID- 18330316
TI  - [Determination of trace arsenic in Chinese traditional medicine by hydride
      generation atomic fluorescence spectrometry].
AB  - A hydride generation atomic fluorescence spectrometry method was developed for
      the determination of trace arsenic in CTM. A digestion system using HNO3-H2O2
      under high pressure was applied for the pretreatment of the samples. The
      experimental conditions were optimized. Under the optimum conditions, there was a
      good linear relationship between the fluorescence intensity and arsenic
      concentration in the range of 0-80 microg x L(-1) with a correlation coefficient
      of 0.9999, while the detection limit was 0.069 microg x L(-1). Trace arsenic in
      the standard reference substance (GBW08501) was determined incording this way and
      the results for six times of analysis were in good agreement with certified
      value. The authors also studied the arsenic contents in three kinds of CTM by the
      working curve method and the results were satisfactory.

PMID- 18330317
TI  - [Determination of nutrition elements in Yak milk powder by atomic absorption
      spectrometry].
AB  - In the present paper, orthogonal design test was planed by changing cinefaction
      temperature, cinefaction time, and the concentration of hydrochloric acid. Yak
      milk powder and milk powder were digested by dry method. The contents of elements
      Ca, Mg, Fe, Cu, Zn, Mn, K and Na were determined by flame atomic absorption
      spectrometry. The best conditions for the digestion were obtained as follows: the
      temperature was 510 degrees C, cinefaction time 4 hours, and hydrochloric acid
      concentration 1 : 5. Meanwhile, under the best experimental conditions, the
      recovery ratio of the method in the range of 95.2%-107.3%, and the relative
      standard deviations were 0.38%-3.86% (n=6). The experimental results proved that
      Yak milk powder is valuable and nutritious food, and has rich nutrition elements.

PMID- 18330318
TI  - [Determination and comparison of trace elements in four sorts of Bulbus
      Fritillariae by microwave digestion-atomic absorption spectrometry].
AB  - The contents of elements such as Zn, Fe, Mn, Cu, Na, Mg, K, Ca, As, Pb, Cd, Co,
      Cr, Sr, and Al in four sorts of Bulbus Fritillariae, namaly from Fritillaria
      thunbergii Miq. (Panan and Ningbo), Fritillaria thunbergii Miq. Var.
      chekiangensis Hsiao et K. C. Hsia and Fritillaria cirrhosa D. Don, were
      determined by flame atomic absorption spectrometry (FAAS) and graphite furnace
      atomic absorption spectrometry (GFAAS) respectively. The effect of different
      microwave digestion conditions on the analysis results was reviewed, and optimal
      condition for using atomic absorption spectrophotometry was determined. Principal
      component analysis (PCA) was applied taking trace elements contents as indexes.
      The results revealed that microwave digestion was a simple, rapid, digestion
      complete, and low blank value method, and the measurement result is satisfactory.
      The experimental results indicated that the linear relationships for different
      elements within the limits of working curve were good. The RSDs were all smaller
      than 3.97%. The addition standard rates of the procedure was between 91.0% and
      108.7%. Principal component analysis has the application value of reflecting the
      differences in trace elements contents in various samples.

PMID- 18330319
TI  - [Exploration of quality control of inorganic elements in Chinese herbal medicines
      for stimulating blood circulation and relaxing muscles and joints by atomic
      absorption spectrophotometry].
AB  - Researches have shown the close relationships between inorganic elements and
      curative efficiencies of various Chinese herbal medicines. Yet, in studies of
      chemical composition and quality control of Chinese herbal medicines for
      stimulating blood circulation and relaxing muscles and joints, inorganic
      substances are often overlooked. In order to improve and reestablish the standard
      of quality control of Chinese herbal medicines, the authors attempted a method
      that would incorporate the composition of inorganic elements as part of the
      quality control. In the present study, the authors used atomic absorption
      spectrophotometry to measure the contents of fifteen inorganic elements, namely,
      Cu, Ca, Fe, K, Mg, Mo, Ni, Sr, V, Mn, Zn, Na, Cr, Cd, and Hg, in several Chinese
      herbal medicines, including Da Huo Luo Wan. The authors then discussed the
      relationship between these inorganic elements and curative efficiencies of these
      Chinese herbal medicines. By comparing the levels of inorganic elements found in
      Da Huo Luo Wan with those found in other Chinese herbal medicines used in the
      study, it was revealed that trace elements, Fe, Cu, Mn, and Zn, contribute to the
      curative efficiency of Da Huo Luo Wan. The authors' results showed that the
      amounts of trace elements Fe, Cu, Mn and Zn found in Chinese herbal medicine Da
      Huo Luo Wan are related to the following curative effects of Da Huo Luo Wan:
      relieving rheumatism, rectifying breathing and alleviating phlegm, stimulating
      blood circulation and relaxing muscles and joints. The measurement and analysis
      of inorganic elements in Da Huo Luo Wan will also provide evidences and
      references for the fingerprint establishment of Da Huo Luo Wan in the future.

PMID- 18330320
TI  - [Determination of eight trace elements in the Swertia davidii Franch by flame
      atomic absorption spectrometry].
AB  - The effects of different sample digestives on the determination of Swertia
      davidii Franch are compared. Eight trace elements in the Swertia davidii Franch
      were determined by flame atomic absorption spectrometry. The result shows that
      the RSD and recovery are better if the Swertia davidii Franch was digested with
      HNO3-HClO4 (5 : 1) mixed acid. The experimental results show that the detection
      limits were all smaller than 0.097 microg x mL(-1), the RSDs (n=8) all smaller
      than 2.34%, and the addition standard recovery (ASR) (n=8) was 89.32%-106.65% for
      all the elements.

PMID- 18330321
TI  - [Simultaneous determination of calcium and magnesium by calculative
      spectrophotometric complexometric titration].
AB  - A new spectrophotometric complexometric titration method coupled with
      chemometrics for the determination of mixtures of metal ions has been developed.
      In the method described here, the titrant is a mixture of EDTA and two
      indicators. In the process of titration, both the volumetric addition of titrant
      and the progress of titration reaction can be characterized simultaneously by
      chemometric calculation with the absorption spectra, and then the titration
      curves can be obtained. With the titration curves, a matrix equation can be
      established, and thus the concentration of each component in the mixture of metal
      ions can be calculated with principal component regression. The method only needs
      the information of absorption spectra to obtain the analytical results, and is
      free of volumetric measurements. So the method is simple, convenient and precise,
      and has been applied to the simultaneous determination of mixtures of calcium and
      magnesium using malachite green and Cu-PAN as indicators with satisfactory
      results.

PMID- 18330322
TI  - Critical appraisal of currently used oxytocin regimen and prospects.
AB  - About half a century passed since synthetic oxytocin use to induce or augment
      labour came in to clinical practice; however, so far there is no international
      consensus on the dose regimen. In most studies, high dose regimen and long
      increment interval were found to have much desirable obstetric outcomes (short
      induction-to-delivery time, low caesarean section rate, less fetal and maternal
      risk). Although different centres use different starting and increment dose
      regimen, the stepwise increment till the maximum dose achieved (20 mu/min for low
      dose and 42 mu/ min for high dose regimen) is the common feature. The oxytocin
      regimen practiced in Ethiopia is unique: different regimen is used for nulliparas
      and multiparas; half dose of induction is for augmentation; the maximum dose
      achieved at the middle of the cycle is nearly twice (74.3-85.4 mu/min) the
      maximum dose other centres use (42 mu/ min). Dose increment is also so bizarre
      and swinging. The maximum dose achieved at the middle of the three cycles is not
      maintained In general, to the best of author's accessible resources, the origin
      of this regimen is not clear and can not be traced to any scientific literature.
      Therefore, easily applicable regimen for Ethiopian set up is presented for
      clinical trail.

PMID- 18330323
TI  - Currently used oxytocin regimen outcome measures at term & postterm. I: Outcome
      indicators in relation to parity & indication for induction.
AB  - INTRODUCTION: Although induction of labour with oxytocin is a daily practice at
      public as well as private health institutions, to the best of our knowledge,
      there is no published study on induction in Ethiopia. OBJECTIVE: To assess the
      oxytocin dose required to achieve adequate uterine contraction, the time interval
      between initiation of oxytocin and adequate contraction achieved and the time
      lapsed between initiation of induction and vaginal delivery. METHODOLOGY: A two
      year retrospective case-series study was done to evaluate the currently used
      oxytocin regimen outcome measures at Gandhi and St. Paul's hospitals. Oxytocin
      level in milliunit/minute to achieve adequate uterine contraction, time lapsed to
      establish labour and deliver vaginally, Bishop Score, and indications for
      induction were some of the variables included. RESULTS: Five hundred fifty two
      women induced at term and post term (55.8% nulliparas and 44.2% multiparas) were
      reviewed with overall elective to emergency induction ratio about 1:1. The first
      three indications for induction were post term (P < 0.05), term premature rupture
      of fetal membranes and hypertension (P = 0.005). Spontaneous vertex delivery
      (46.4%), caesarean section for failed induction (28.4%) and fetal distress (9.6%)
      were the top modes of delivery in both nulliparas and multiparas. Equal
      proportion of nulliparas and multiparas established labour (84.1% vs 84.8%) with
      mean oxytocin level in mu/min 33.6 +/- 21.9 and 17.2 +/- 11.4 and mean time
      lapsed in hours 2:10 +/- 1:30 and 2:10 +/- 1:10 between initiation of induction
      and adequate uterine contraction, respectively. More than two-thirds of
      multiparous and half of nulliparous women achieved adequate uterine contractions
      with 20-mu/min and less oxytocin infusion among the total women (84.4%) who were
      diagnosed to have adequate uterine contractions. CONCLUSION: Although the
      starting, increment and maximum oxytocin regimen for nulliparas and multiparas
      were different but with parallel Bishop Score, the induction initiation to
      vaginal delivery time was almost comparable. Very high oxytocin dose for
      nulliparas wasn't superior to multiparas dose.

PMID- 18330324
TI  - Currently used oxytocin regimen outcome measures at term & postterm. II: Outcome
      indicators in relation to Bishop Score & other covariates.
AB  - BACKGROUND: The effect of Bishop Score on labour induction outcome is extensively
      studied and partly known. However, the length of induction before failed
      induction declared is a controversial issue. Furthermore, to our knowledge,
      stratified Bishop Score in relation with stratified mode of delivery, induction
      initiation to vaginal delivery time, and variable cervical dilatation change
      among failed inductions were not assessed before. In literature, the maximum
      oxytocin in milliunit/minute also does vary from 20 to 42 milliunit/minute. Lack
      of published study assessing the separate oxytocin dose regimen for nulliparas
      and multiparas in Ethiopia, for which we could not find such regimen in
      literature, motivated us to review a two year case-series at term and post term.
      OBJECTIVE: To evaluate the relation of Bishop Score and induction outcome
      measured by length of induction initiation-vaginal delivery time and modes of
      delivery in Gandhi and St. Paul's hospitals. METHODS: Time lapsed to deliver
      vaginally or to declare failed induction, the maximum oxytocin level in
      milliunit/ minute infused before subjecting for abdominal delivery, length of
      induction and mode of delivery were some of the variables assessed. RESULT: The
      Bishop score of 42.0% and 42.4% of the 552 women medically induced were assessed
      to have 0-5 and 6-8, respectively. Over all, among the 0-5 Bishop Score group,
      45.7% were induction failures. To be specific, out of 157 total failures, 0-5
      Bishop Score group accounted for 67.5% (P < 0.0001). Bishop score was found to
      have an inverse relation with failed induction, and negative correlation (r = 
      0.22) with length of labour among vaginal deliveries. Failure to bring about
      cervical dilatation and unable to establish adequate uterine contractions (45.2%
      and 54.8%, respectively) were the two reasons for failed inductions. Although the
      range was wide (2:50 - 21:0), the mean length of induction in hours in both
      nulliparas and multiparas prior to decision for failed induction was comparable
      (9:45 +/- 3:20 vs 9:25 +/- 2:55). The maximum oxytocin infused in mu/min for
      nulliparas and multiparas was 73.4 and 36.7 but was not linear; stepwise increase
      with each increase in the infusion rate was not the finding. CONCLUSION:
      currently used oxytocin regimen protocol was associated with high induction
      failure.

PMID- 18330325
TI  - Neonatal gastrointestinal surgical emergencies: a 5- year review in a teaching
      hospital Addis Ababa, Ethiopia.
AB  - OBJECTIVE: A five year retrospective review of medical records of newborns
      admitted for gastrointestinal surgical emergencies was done. This study was
      intended to see the pattern of presentation, mode of intervention and surgical
      outcome of these cases and for provision of feed-back to the surgeon-pediatrician
      team who are involved in the care of such newborns. METHODS: The study included
      cases admitted to the Neonatal Unit of the Department of Pediatrics and Child
      Health, Tikur Anbessa Specialized Hospital, Addis Ababa, during the period of
      January 1, 1997 to December 31, 2001. RESULTS: A total of 60 cases admitted
      during the above-mentioned period were reviewed. Thirty-six (60%) were males, 23
      (38%) were females, while one newborn had ambiguous genitalia. Imperforate anus
      has accounted for 27 (45%) of the 60 cases; jejunoileal atresia and esophageal
      atresia with or without tracheoesophageal each accounted for 12 (20%) cases;
      while 9 (15%) had other lesions. Of the 60 cases surgical intervention was
      performed on 43 (72%) newborns. Of the 12 newborns with esophageal atresia with
      or with out tracheoesophageal fistula. only one newborn was discharged alive; 7
      out of 12 newborns with jejunoileal atresia died, 4 cases discharged improved
      while the outcome for 1 newborn was not known. Of the newborns with imperforate
      anus, 8 (47%) of the 17 with the high type and 1 (10%) of the 10 with low-type
      died CONCLUSION: Early diagnosis, availability of diagnostic service and prompt
      surgical intervention with optimal pre- and post-operative care are necessary to
      increase survival of newborns with such problems.

PMID- 18330326
TI  - Surgical management of 234 patients with hydatid disease: the Tikur Anbessa
      Hospital experience.
AB  - OBJECTIVE: The aim of this study was to evaluate the pattern and surgical
      management of hydatid disease. METHODS: A hospital based retrospective cross
      sectional analysis was conducted in Tikur Anbessa Hospital, department of
      surgery, Addis Ababa, Ethiopia. Patients' medical records and operation theater
      registers of 234 patients operated upon for hydatid disease between September
      1995 and August 2005 were analyzed RESULTS: One hundred and twenty three patients
      were male and 111 female. Their age ranged from 13-69 years, with median and peak
      age of incidence of 30 and 21-30 years respectively. Hundred forty five (62.0%)
      patients were from rural population. Significant number of patients (40.6%) came
      from Oromiya regional state (p < 0.004). The most common presenting symptoms were
      pain in 206/234 (88.0%) patients with hydatidosis, mass or organomegally in
      106/141(75.2%) patients with intraabdominal hydatid diseases, cough in 91.2% and
      expectoration in 83.3% of cases of thoracic hydatidosis. Liver and lung (79.6%)
      are the most commonly affected organs. More than one organ involvement was seen
      in 13.7% of cases. Ultrasonography and chest roentgenography were the main
      modalities of investigation of abdominal and thoracic hydatidosis respectively.
      Surgical techniques employed for removal of cysts was evacuation in 181 (67.3%).
      capitonnage in 167 (62.1%) and pericystectomy in 47 (17.5%) organs. In 191
      (81.6%) patients the postoperative course was uneventful while 15.8% developed
      postoperative complications. There were six deaths. The follow up period ranged
      from 1 month to 3 years (mean 5.6 months). CONCLUSION: Hydatidosis is not
      uncommon in rural communities of Ethiopia particularly in Oromiya. Complete
      excision of the disease processes with maximum preservation of tissue is safe and
      ideal for most patients with hydatidosis.

PMID- 18330327
TI  - Surgical treatment of achalasia cardia in Tikur Anbessa Hospital, Ethiopia.
AB  - OBJECTIVE: This review aims to evaluate 61 patients with achalasia cardia treated
      with Heller's cardiomyotomy in Tikur Anbessa Hospital (TAH). METHODS: A hospital
      based cross sectional analysis was conducted in TAH, Department of Surgery, Addis
      Ababa, Ethiopia between January 1996 and December 2005. Medical records and
      operation theater registers of 61 patients operated upon for achalasia cardia
      were analyzed retrospectively. RESULTS: Thirty-four were male and twenty-seven
      female with mean age of 25 years (range 9-58). All had dysphagia to solid foods.
      Thirty-one (50.8%) patients had weight loss. The diagnosis of achalasia cardia
      was confirmed in 60 (98.4%) patients by barium swallow; in 23/25 (92.0%) by
      esophagoscopy. Cardiomyotomy was performed through transabdominal (83.6%) and
      transthoracic (16.4%) approaches. Immediate postoperative course was uneventful
      in 52 (85.2%) patients, while 9 (14.8%) patients developed immediate
      postoperative complication. There was no in-hospital mortality. Median operation
      time and hospital stay were 60 minutes and 7 days respectively. Late
      complications occurred in 7/52 (13.5%) patients, Gastroesophageal Reflux Disease
      (GERD) (9.6%) being the most common. A very good palliation of dysphagia was
      achieved in 88.5% of cases (p < 0.0001). CONCLUSION: Significant improvement in
      dysphagia of patients with achalasia cardia following modified Heller's myotomy
      alone is possible in majority of the patients.

PMID- 18330328
TI  - Cost of hospitalization of diabetic patients admitted at Tikur Anbessa
      Specialized Hospital, Addis Ababa, Ethiopia.
AB  - OBJECTIVE: In Ethiopia the problems passed by diabetes is increasing for the last
      two to three decades. This indicates that diabetes is becoming a major economic
      factor in drug use and bed occupancy. So far there has been no study conducted to
      evaluate the cost of care among Ethiopian diabetic patients. This study aimed at
      assessing the cost of hospitalization of diabetic patients. METHODS: A case
      control study was conducted on consecutive 146 diabetic patients and 142 non
      diabetic controls admitted to the medical wards of Tikur Anbessa Specialized
      Hospital. Every first non-diabetic patient who was admitted to the same ward on
      the same day or in the subsequent days was taken as a control group. RESULTS: The
      average total cost of hospitalization of cases was significantly higher than the
      controls with mean cost of 1109.7 +/- 1026.4 for cases and 872.9 +/- 828.3 Birr
      for controls respectively, (p < 0.03). A large proportion (57%) of the total cost
      was utilized for treatment of acute and chronic complications of diabetes. The
      average treatment and laboratory cost were significantly higher among cases
      compared to controls (p = 0.013 and p = < 0.001 respectively). However, when
      adjusted by age, sex, address and history of hypertension and renal diseases, the
      average cost of laboratory investigation remained significantly higher for cases.
      CONCLUSION: The current study demonstrated that the direct cost of
      hospitalization of diabetic patient is significantly higher than non diabetics.
      The study showed that substantial proportion of the total cost of admission is
      utilized for treating acute and long term complications. This study warrants
      further research, attention of the health policy makers and health providers for
      future planning of prevention, diagnosis and treatment of diabetes.

PMID- 18330329
TI  - Knowledge, attitude and practice of home-based care for HIV/AIDS patients by
      their family/ caregivers at Jimma Town.
AB  - BACKGROUND: About 1.5 million people are currently living with HIV/AIDS in
      Ethiopia-one of the largest HIV infected populations in the world. The current
      prevalence rate of infection is estimated at 4.4% nationally. Hospital bed
      occupancy rate due to AIDS has reached over 50% in urban hospitals creating a
      severe burden to the health service system in the country, or else US $3.4
      million is needed in order to increase their bed capacity. Here arises the need
      to look for a better way of caring for people living with HIV/AIDS. Home care
      would thus offer the only feasible option for this need as it can mobilize the
      considerable reservoir of caring and sympathy that exists within a community
      beyond that of cost cutting. The study was conducted to determine the knowledge,
      attitude and practice of family/caregivers regarding home-based care for people
      living with HIV/AIDS. METHODS: This was a cross-sectional community-based study
      conducted among 274 family/caregivers who were giving care for people living with
      HIV/AIDS in urban setting of Jimma town from June - August 2005. A structured and
      pre-tested questionnaire was used to collect data on socio-demographic
      characteristics, knowledge and attitude towards home based care practice. Data
      collection was done by interviewing family/caregivers at their respective houses
      and analyzed using SPSS for windows version 11.0. RESULTS: Over three fourth of
      the studied subjects (91.6%) were knowledgeable about home based care and 88.7%
      showed favorable attitude. Ninety two point eight percent agreed that home is a
      better place for the care of PLWHA than hospital. Single caregivers were about
      four times more likely to be knowledgeable about home care as compared to their
      counterparts (OR = 3.98 (95% CI: 0.50, 88.08), but the finding was not
      statistically significant (p > 0.05). Neighbors and friends were two times more
      likely to have favorable attitude towards HBC as compared to family members, OR =
      1.96 (95% CI: 0.74, 5.21) but, the finding is not statistically significant (p >
      0.05). CONCLUSION: The study highlighted that the majority of family
      members/caregivers have good knowledge and favorable attitude towards HBC and
      over half favored this care. Therefore, appropriate use of the above promising
      findings and experience of innovative approaches of HBC from other countries is
      recommended for further, more organized and effective home-based care practice.

PMID- 18330330
TI  - Assessment of the implementation of HIV-rapid test kits at different levels of
      health institutions in Ethiopia.
AB  - OBJECTIVE: Evaluation and monitoring of Human Immunodeficiency Virus (HIV)
      testing reagents at the point of service is helpful to prevent the occurrence of
      problems related to testing and interpretation. To evaluate the implementation of
      HIV rapid test kits at the point of services in voluntarily counseling and
      testing (VCT) and diagnostic centers in Ethiopia. METHODS: The assessment was the
      third phase of evaluation of HIV rapid test kits in Ethiopia followed from phase
      I and phase-II. Known proficiency testing panels, well-structured questionnaire
      (addressing type of tests, human resource and problems related to tests), onsite
      supervision and retesting of samples collected from sites were used to evaluate
      the performances of reagents and laboratories. RESULTS: Forty-four health
      institutions were included. Thirty-six (90.0%) health institutions had trained
      human resource on HIV testing. In 27 (61.4%) three types of HIV rapid test kits
      (Determine, Capillus and Unigold) were available. Serial-algorithm was used in
      all the laboratories. In 31 (70.4%) of them external quality control specimens
      were not used. Twenty two (50.0%) of the laboratories reported frequent shortage
      of reagents. All (100%) were able to identify negative specimens distributed.
      Positive proficiency panel samples were identified in 37 (94.8%) of the 39
      laboratories. There was 98.3% agreement at a screening level between the sites
      and the central laboratory. Rate of discrepancy between screening and
      confirmatory assays was found to be 3.0% and 2.1% at the sites and at central
      laboratory, respectively. CONCLUSION: The test kits showed a good performance at
      the point of services in the field sites. However, continuous assessment of HIV
      test kits at the point of service and training of professionals on newly arrived
      techniques are recommended to have effective testing performance with acceptable
      sensitive and specific testing algorithm. Effective quality assurance program
      should be in place to support programs such as VCT, prevention of mother-to-child
      transmission and antiretroviral therapy.

PMID- 18330331
TI  - Efficacy of mebendazole and albendazole for Ascaris lumbricoides and hookworm
      infections in an area with long time exposure for antihelminthes, Northwest
      Ethiopia.
AB  - OBJECTIVE: The efficacy of mebendazole and albendazole in the treatment of
      Ascaris lumbricoides and hookworm infections was evaluated in school children in
      an area with long time exposure for broad spectrum anthelminthic drugs. RESULTS:
      Mebendazole exhibited cure rates of 90.6% and 83.5%; egg reduction rates of 96.7%
      and 94.2% against Ascaris lumbricoides and hookworm infections respectively.
      Albendazole showed a cure rate of 83.9% and egg reduction rate of 96.3% against
      Ascaris lumbricoides and a cure rate of 84.2% and egg reduction rate of 95%
      against hookworm infection. Albendazole appeared to be more effective against
      hookworm infection (egg reduction rate of 95% versus 94.2%, p = 0.04).
      CONCLUSIONS: Mebendazole and albendazole showed reduced efficacy against Ascaris
      lumbricoides and hookworm infections at the recommended doses. This may be a sign
      for emergence of drug resistance in this region. Care in routine use of the
      anthelminthes and continuous drug efficacy surveillance is recommended.

PMID- 18330332
TI  - Androgen insensitivity syndrome: a case report.
AB  - This report refers to a rare case of complete androgen insensitivity syndrome
      that had presented at the age of 35 years with complaint of abdominal mass,
      primary amenorrhea and infertility to Jimma University Hospital. A well-developed
      breast with absence of axillary and pubic hair was seen on examination. There was
      also an abdominal mass arising from the pelvis occupying the hypogastric and
      right iliac region. Additionally, there was a reducible mass of 5 by 4 c.m at the
      left inguinal region. She had a normal female external genitalia with blindly
      ending vagina of about 4 c.m long. Laporotomy was done and a grayish white solid
      mass of 20 by 10 c.m. was found and removed. The reducible mass in the left
      inguinal canal was also removed surgically which was followed by herinorraphy.
      There were no ovaries or any other internal female genital organs identifiable.
      Histopathology of the tumor showed features of seminoma while the mass in the
      inguinal canal was consistent with testis. Literature review on diagnosis,
      differential diagnosis and management of androgen insensitivity syndrome was made
      and discussed. This is the first case report of androgen insensitivity syndrome
      (AIS) in an Ethiopian patient.

PMID- 18330333
TI  - A case of hepatoblastoma; uncommon hepatic neoplasm occurring at unusual age.
AB  - A seven-year-old male patient presented to Tikur Anbessa Hospital with right
      upper quadrant pain of nine months and right upper quadrant swelling of six
      months duration. He was having loss of appetite and significant weight loss.
      Physical examination revealed an enlarged liver. He was worked up with laboratory
      and radiologic investigations. Ultrasound (US) was done and findings were
      suggestive of the diagnosis and Computed Tomography (CT) scan was done, and was
      also diagnostic and confirmed by the final histological diagnosis. We present and
      discuss a case with an uncommon hepatic neoplasm occurring at unusual age.

PMID- 18330334
TI  - The rare case: the solid pseudopapillary neoplasm of the pancreas [corrected].

PMID- 18330336
TI  - Put evidence into practice to manage depression.

PMID- 18330335
TI  - Treating the taboo: cancer control in developing countries.

PMID- 18330337
TI  - Virus related to smallpox may help fight cancer.

PMID- 18330338
TI  - ONS has the responsibility and opportunity to affect the global burden of cancer.

PMID- 18330339
TI  - The 2008 Medicare fee schedule.

PMID- 18330340
TI  - Project access: giving back at home.

PMID- 18330341
TI  - Current procedural terminology: changes for 2008.

PMID- 18330342
TI  - Project New Orleans.

PMID- 18330343
TI  - Medicare pay-for-reporting program to continue in 2008.

PMID- 18330344
TI  - Resuscitating research funding.

PMID- 18330345
TI  - Closing the circle. Jeffrey V. Ravetch, M.D., Ph.D. Interviewed by Lynne
      Lederman.

PMID- 18330346
TI  - Combining allele-specific fluorescent probes and restriction assay in real-time
      PCR to achieve SNP scoring beyond allele ratios of 1:1000.
AB  - TaqMan-nuclease assays are widely used for the qualitative detection of single
      nucleotide polymorphisms (SNPs) and the determination of biallelic states in
      pooled or heterozygous DNA samples. These assays are highly specific,
      reproducible, and suitable for high-throughput approaches. A crucial limitation
      of this method, and others, is the detection qf minor allele frequencies with
      detection limits of generally 3% to 9% for minor allele contributions. Here we
      describe the combination of customized TaqMan-nuclease assay and allele-specific
      restriction to increase the sensitivity of this method, allowing the qualitative
      detection of allele contributions as low as 0.05%.

PMID- 18330347
TI  - Assays for the rapid and specific identification of North American Yersinia
      pestis and the common laboratory strain CO92.
AB  - We present TaqMan-minor groove binding (MGB) assays for an SNP that separates the
      Yersinia pestis strain CO92 from all other strains and for another SNP that
      separates North American strains from all other global strains.

PMID- 18330348
TI  - In-frame deletion of Escherichia coli essential genes in complex regulon.
AB  - A conditional knockout-rescue system was developed to construct an in-frame
      deletion strain ofEscherichia coli essential genes. The target was flanked with
      marker genes and FRT (FLP recognition target) sites, and a plasmid containing
      arabinose-induced FLP recombinase was transformed. After arabinose induction,
      cells could survive only when target protein activity was provided in trans. We
      selected three essential genes as targets, yaeT, fabZ, and dnaE, which are
      components of the complex eight-gene regulon yaeT-hlpA-lpxD-fabZ-lpxA-1pxB-rnhB
      dnaE. Deletion of these three genes exhibit no polar effects on their adjacent
      genes in terms of cell viability, meaning that this system not only allows for
      the simplified study of protein interactions and homolog screening in other
      organisms, but also facilitates the null mutant construction of essential genes.

PMID- 18330349
TI  - Highly efficient deletion method for the engineering of plasmid DNA with single
      stranded oligonucleotides.
AB  - The lamda phage Red recombination system has been used to modify plasmid,
      bacterial artificial chromosome (BAC), and chromosomal DNA in a highly precise
      and versatile manner Linear double-stranded DNA fragments or synthetic single
      stranded oligonucleotides (SSOs) with short flanking homologies (<50 bp) to the
      target loci can be used as substrates to direct changes, including point
      mutations, insertions, and deletions. In attempts to explore mechanistic bases
      under this recombination process, we and others have previously identified
      factors that influence SSO-mediated single base substitutions. In this report, we
      focus our study on SSO-mediated deletion on plasmids. We found that SSOs as short
      as 63 bp were sufficient to mediate deletion as long as 2 kb with efficiency
      higher than 1%. Strand bias was consistently observed, and SSOs with sequences
      identical to the nascent lagging strand during replication always resulted in
      higher efficiency. Unlike SSO-mediated single nucleotide substitution, homology
      on each side of SSO flanking the fragment to be deleted was important for
      successful deletion, and abolishing the host methyl-directed mismatch repair
      (MMR) system did not lead to detectable changes in deletion efficiency. Finally,
      we showed that by optimizing its design, SSO-mediated deletion was efficient
      enough to make it possible to manipulate plasmids without selectable markers.

PMID- 18330350
TI  - Scanning conductance microscopy investigations on fixed human chromosomes.
AB  - Scanning conductance microscopy investigations were carried out in air on human
      chromosomes fixed on pre-fabricated SiO2 surfaces with a backgate. The point of
      the investigation was to estimate the dielectric constant of fixed human
      chromosomes in order to use it for microfluidic device optimization. The phase
      shift caused by the electrostatic forces, together with geometrical measurements
      of the atomic force microscopy (AFM) cantilever and the chromosomes were used to
      estimate a value for the dielectric constant of different human chromosomes.

PMID- 18330351
TI  - A genome walking strategy for the identification of eukaryotic nucleotide
      sequences adjacent to known regions.
AB  - Determination of nucleotide sequences adjacent to a known region is a recurring
      need in many genome scale studies. Various methods have been developed based on
      PCR techniques in order to fulfill this aim and overcome the time-consuming
      approach of screening genomic libraries. Usually these protocols rely on specific
      requirements and strategies, such as the presence of suitable nucleotide
      restriction sites and ligation of specific single- or double-strand linkers, thus
      limiting their application to a certain extent. In this paper we present an
      alternative PCR-based protocol, consisting of four main steps: (i) extension of a
      sequence-specific primer; (ii) 3'-tailing of extended single-strand DNA; (iii)
      PCR; and (iv) nested PCR amplifications. This method, which appears to be a valid
      alternative to the other PCR-based protocols, was used for the identification of
      sequences flanking the cDNA encoding region of the Lhcb 1.1 gene (one member of
      the multigene family coding for the light harvesting protein Lhcbl) in the
      spinach genome.

PMID- 18330352
TI  - Real-time viability assay based on 51Cr retention in adherent cells.
AB  - The chromium (51Cr) release assay has been widely used for viability
      measurements, even though it has major disadvantages such as high manual workload
      and poor time resolution. By the use of LigandTracer 51Cr release viability
      measurements on adherent cells can be significantly simplified and improved.
      LigandTracer enables a time-resolved detection of 5SCr in target cells, with the
      result that the effect of toxic material is updated continuously throughout the
      experiment. Here we explain the principle behind this novel real-time viability
      assay and show viability curves for known toxic compounds on A431 and
      U343MGaCl2:6 cell lines.

PMID- 18330353
TI  - An oligonucleotide microarray for multiplex real-time PCR identification of HIV
      1, HBV, and HCV.
AB  - We describe a novel microarray-based approach for simultaneous identification and
      quantification of human immunodeficiency virus type 1 (HIV-1) and hepatitis B and
      C viruses (HBV and HCV) in donor plasma specimens. The method is based on
      multiplex real-time RT-PCR performed within the microarray hydrogel pads. Double
      stranded amplification products are simultaneously detected using nonspecific
      SYBR Green I dye due to the reaction run in separate pads bearing 5'-immobilized
      specific primers. Both the sensitivity and specificity of the assay, based on 132
      blood specimens analyzed, were 100% (56, 26, and 8 specimens were seropositive to
      HBV HCV and HIV-1, respectively; 22 were positive to both HIV-1 and HCV and 2
      positive to all three viruses; 18 samples were pathogen-negative). The dynamic
      range of the quantitative analysis covered a six-order interval ranging from 100
      to 106 genome equivalents per assay. The 95% detection limits were 14 gEq for HIV
      1, 10 gEq (1.7 IU) for HBV, and 15 gEq (7.5 IU) for HCV per assay. The proposed
      approach is considered to be versatile and could be adapted for simultaneous
      identification and quantification of numerous genetic targets.

PMID- 18330354
TI  - Mammalian cell-seeded hydrogel microarrays printed via dip-pin technology.
AB  - Although significant advances have been made in the development of DNA and
      protein microarrays, less effort has been put toward developing mammalian cell
      microarrays. Such cellular microarrays may be useful in examining the effects of
      biological or chemical agents on cells, particularly in drug development and
      toxicological applications. Here, mammalian cell-seeded hydrogel microarrays were
      created using two different commercial microarrayers, with four different pin
      types. Human dermal fibroblasts were used here as a model cell type, seeded
      within polyethylene glycol-based hydrogels similar to those under investigation
      as tissue engineering scaffolds, which serve as synthetic extracellular matrices
      for the cells. Spot sizes of the hydrogels were found to vary with pin type.
      Multiple touches on a slide following a single dip in the reservoir print
      solution led to decreasing spot size with each touch; therefore, subsequent
      microarrays were printed with single touches after a dip. Individual pins of the
      same type and tip diameter had significantly different spot sizes, likely due to
      wear of the pins at the tip. However there was high run-to-run reproducibility
      between subsequent microarrays. Cell viability varied with pin type, and the
      number of cells per spot varied with cell density in the print solution, as
      expected.

PMID- 18330355
TI  - Rapid capture of DNA targets.
AB  - A rapid capture technique was developed to efficiently isolate specific DNA
      targets from a variety of genomes. The specificity can be easily adapted to any
      target for which partial sequence is known, allowing for the isolation of a wide
      set of target molecules from either characterized or uncharacterized genomes.
      These targets include but are not limited to transposable elements,
      microsatellites, repetitive sequences, and possibly unique sequences.
      Additionally, because the thermodynamics of nucleic acid hybridizations differ
      from processes such as PCR, a wider variety of targets with a range of mismatches
      to any customized probe can be isolated. Further this method allows sequences
      flanking known internal regions to be co-isolated, facilitating the development
      of flanking primers for downstream applications. Considerable reduction in the
      frequency of nonspecific binding between key components (background) obviates the
      need for subsequent screening steps. Rapid capture of DNA targets quickly
      provides information about target and flanking sequences.

PMID- 18330356
TI  - Construction and characterization of a normalized yeast two-hybrid library
      derived from a human protein-coding clone collection.
AB  - The nuclear yeast two-hybrid (Y2H) system is the most widely used technology for
      detecting interactions between proteins. A common approach is to screen specific
      test proteins (baits) against large compilations of randomly cloned proteins
      (prey libraries). For eukaryotic organisms, libraries have traditionally been
      generated using messenger RNA (mRNA) extracted from various tissues and cells.
      Here we present a library construction strategy made possible by ongoing public
      efforts to establish collections of full-length protein encoding clones. Our
      approach generates libraries that are essentially normalized and contain both
      randomly fragmented as well as full-length inserts. We refer to this type of
      protein-coding clone-derived library as random and full-length (RAFL) Y2H
      library. The library described here is based on clones from the Mammalian Gene
      Collection, but our strategy is compatible with the use of any protein-coding
      clone collection from any organism in any vector and does not require inserts to
      be devoid of untranslated regions. We tested our prototype human RAFL library
      against a set of baits that had previously been searched against multiple cDNA
      libraries. These Y2H searches yielded a combination of novel as well as expected
      interactions, indicating that the RAFL library constitutes a valuable complement
      to Y2H cDNA libraries.

PMID- 18330357
TI  - A flyer's surprise.

PMID- 18330358
TI  - Staffing. Powering up the workforce pipeline in New Orleans.

PMID- 18330359
TI  - Telecommunications. Rural areas poised to bolster telehealth.

PMID- 18330360
TI  - Patient safety. In the wake of safety concerns, hospitals revise CT scan
      protocols.

PMID- 18330361
TI  - Other voices. Quality, safety top New Joint Commission Chief's agenda. Interview
      by Matthew Weinstock.

PMID- 18330362
TI  - Practical ethics. Should you play ball?

PMID- 18330363
TI  - Technology. Patients learn to love remote monitoring.

PMID- 18330364
TI  - Finding ways to improve behavioral health.

PMID- 18330365
TI  - Physician recruitment. Garrison Keillor: doctor magnet.

PMID- 18330366
TI  - Physicians. Country doctor saves small-town hospital.

PMID- 18330367
TI  - Emergency care. Trauma centers face funding, staffing woes.

PMID- 18330368
TI  - Heading for an iceberg?

PMID- 18330369
TI  - A national health IT policy proves elusive.
AB  - We need a cohesive national policy to promote health care information technology.
      So what's holding us up? And will we ever agree on a viable strategy?

PMID- 18330370
TI  - The changing role of the CMIO.
AB  - Chief medical information officer is a relatively new position at most hospitals,
      but the job is changing as rapidly as the technology they oversee. This foldout
      describes CMIOs' key responsibilities, desirable traits and barriers to
      effectiveness.

PMID- 18330371
TI  - IT at a crossroads.
AB  - Health care is not the laggard it used to be when it comes to information
      technology. But as hospitals' IT use matures, new risks and tensions emerge.

PMID- 18330372
TI  - Is America finally ready for reform?
AB  - All the talk this political season about fixing health care may feel like deja
      vu. Anybody remember the '90s? Skeptics beware: Reform could happen this time
      around.

PMID- 18330373
TI  - Can we really save 5 million lives?
AB  - Hospitals leapt at the challenge to save 100,000 lives through evidence-based
      medicine. Now that the goal is dramatically higher, how are hospitals responding?

PMID- 18330374
TI  - Trustees take on quality.

PMID- 18330375
TI  - Punitive damage award of $5 million reduced. Mobile Infirmary Assn. v. Tyler,
      2007 ALSC 1041484 (09/14/07) So.2d -AL.

PMID- 18330376
TI  - RN removed FHR monitor to make room: $3.8 million verdict. CASE ON POINT: Long v.
      Wader, 2007 ALSC 1041887--08/31/07) So.2d-AL.

PMID- 18330377
TI  - GA: nurse insisted pt. "take" wrong meds: cardiac arrest resulted from OD on
      meds. Wellstar Health System, Inc. v. Painter, SE2d-GA.

PMID- 18330378
TI  - Home health nurse repeatedly stabbed: issue re total disability. CASE ON POINT:
      SAAD's Healthcare Services, Inc. v. Meinhardt 2007 ALCIV 2060302 So.2d-AL.

PMID- 18330379
TI  - Cultivating creativity.

PMID- 18330380
TI  - A day at the airport.

PMID- 18330381
TI  - Fecal incontinence management systems.

PMID- 18330382
TI  - Bridging the gap between poster and manuscript.

PMID- 18330383
TI  - Physical activity: the science of health promotion through tailored messages.
AB  - Sedentary behavior warrants greater attention from rehabilitation nurses because
      physical fitness plays a role in the success of an individualized rehabilitation
      program. With one of every two adults being inactive, rates of sedentary
      lifestyle and obesity are increasing in the United States and are responsible for
      a large portion of our healthcare costs. Conversely, engaging in regular physical
      activity reduces the risks of obesity, premature death, myocardial infarction,
      diabetes, hypertension, colon cancer, depression, and anxiety. Because physical
      activity improves overall function, it is a component of many rehabilitation
      programs. Tailored health messages can be highly effective in helping people
      change unhealthy behaviors by providing information and behavior change
      strategies that are customized for the unique needs, interests, and concerns of
      different people. The rehabilitation nurse can help the client manage long-term
      health problems and maximize wellbeing by tailoring messages geared toward
      increasing physical activity levels. Although the exact mechanism responsible for
      the tailoring effect is not known, it is generally thought that the personally
      relevant information communicated in the message is more likely to improve
      motivation and health behavior change. The goal of a tailored message is to
      produce an individualized communication so that the participant can say, "This
      applies to me". This article examines tailored message approaches geared toward
      engaging people in intentional physical activity.

PMID- 18330384
TI  - Successful implementation of ceiling-mounted lift systems.
AB  - Rehabilitation nurses are well aware of the risks for musculoskeletal injuries
      related to patient handling tasks. Repetitive lifting, turning, and repositioning
      of patients with mobility limitations can take a toll on the nurse. This article
      chronicles integration of ceiling lift technology for patient-handling tasks into
      nursing practice on a spinal cord injury inpatient unit.

PMID- 18330385
TI  - Work experiences of RNs with physical disabilities.
AB  - Registered nurses who consider themselves to be physically disabled were
      interviewed regarding their experiences. Nurses who interview other nurses for
      hire were also interviewed. Participants were gathered from Virginia, Maryland,
      and Maine. Data collection and analysis were conducted using a qualitative
      methodology. Findings indicated that nurses with physical disabilities are
      leaving the workplace, and employers are not typically making accommodations to
      permit nurses to work safely and effectively in the patient-care setting. Nurses
      often hide their disabilities because they fear being rejected for employment and
      being stigmatized by colleagues. Rehabilitation nurses are in an ideal position
      to lead the way to reduce discrimination against nurses with disabilities. Many
      themes emerged from the study and are discussed in this article.

PMID- 18330386
TI  - Older adults' use of postacute and cardiac rehabilitation services after
      hospitalization for a cardiac event.
AB  - The purpose of this study was to describe older patients' use of postacute care
      (PAC) and outpatient cardiac rehabilitation (CR) services after a cardiac event
      and to describe the differences between older adults who use these services and
      those who do not. Under a longitudinal descriptive design, data were collected
      during hospitalization for a cardiac event, 3 and 6 weeks later, and 4 and 6
      months later Of the 60 older adults in the sample, 73% used PAC after discharge.
      Older adults discharged home without PAC services had fewer complications and
      were less depressed than those who used PAC. Older adults discharged to a skilled
      nursing facility had poorer physical function both before the cardiac event and
      during hospitalization. Twenty-five percent participated in outpatient CR. Older
      adults who went to CR were male, had better physical function, and did not live
      alone. Understanding the use of PAC and CR services will help with discharge
      planning and customizing PAC and CR services for older adults to optimize cardiac
      recovery. The integration of CR principles into PAC may be an opportunity to
      enhance recovery for older adults, especially because only a small percentage of
      older adults attend CR.

PMID- 18330387
TI  - State of the science of postacute rehabilitation: setting a research agenda and
      developing an evidence base for practice and public policy. An introduction.
AB  - The Rehabilitation Research and Training Center on Measuring Rehabilitation
      Outcomes and Effectiveness, along with academic, professional, provider,
      accreditor, and other organizations, sponsored a 2-day symposium on the state of
      the science of postacute rehabilitation in February 2007. The aim of this
      symposium was to serve as a catalyst for expanded research on postacute care
      (PAC) rehabilitation so that health policy could be founded on a solid evidence
      base. The goals were to (1) describe the state of our knowledge regarding
      utilization, organization, and outcomes of postacute rehabilitation settings, (2)
      identify methodologic and measurement challenges to conducting research, (3)
      foster the exchange of ideas among researchers, policymakers, industry
      representatives, funding agency staff, consumers, and advocacy groups, and (4)
      identify critical issues related to setting, delivery, payment, and effectiveness
      of rehabilitation services. Plenary presentation and state-of-the-science
      summaries were organized around four themes: (1) the need for improved
      measurement of key rehabilitation variables and methods to collect and analyze
      this information, (2) factors that influence access to postacute rehabilitation
      care, (3) similarities and differences in quality and quantity of services across
      PAC settings, and (4) effectiveness ofpostacute rehabilitation services. The full
      set of symposium articles, including recommendations for future research,

PMID- 18330388
TI  - Don't turn events into disasters.

PMID- 18330389
TI  - The dilemma of donation.

PMID- 18330390
TI  - Trading places.

PMID- 18330391
TI  - Through the eyes of children.

PMID- 18330392
TI  - Reflecting on events.
AB  - This article is intended to give an insight into the world of pre-hospital
      clinical care. For nurses who are not involved with respiratory or emergency
      care, it also illustrates the importance of T pieces in treating patients with
      respiratory problems, and that familiarity and practice are crucial for success
      with these vital, albeit rarely needed, tools.

PMID- 18330393
TI  - Bartholin's abscesses and cysts.

PMID- 18330394
TI  - Nurse led clinical procedures for children.

PMID- 18330395
TI  - Maintaining patient dignity and offering support after miscarriage.

PMID- 18330396
TI  - Barriers to pain management in emergency departments.

PMID- 18330397
TI  - Board's eye view.

PMID- 18330398
TI  - Association between excess bodyweight and intake of red meat and vegetables among
      urban and rural adult Chinese in Nanjing, China.
AB  - The objective of this study was to examine the association of red meat and
      vegetable consumption with excess bodyweight. This is a cross sectional study,
      conducted between October 2000 and March 2001. Participants included 23,316 local
      residents aged 35 and above from 45 administrative villages randomly selected
      from urban and rural areas of Nanjing, China, with a population of 5.6 million.
      The response rate was 90.1%. Logistic regression model was used for the analysis.
      The prevalence of excess body weight, overweight and obesity was 34.1%, 28.2% and
      6.0%, respectively. After adjustment for age, educational attainment, family
      average income, occupational and leisure-time physical activity, smoking,
      drinking, consumption of white meat, consumption of rice and cooking oil as well
      as fruits, participants in the moderate or higher level of red meat consumption
      were more likely to have excess body weight (OR: 1.13 (95% CI =1.02, 1.26) and
      1.15 (1.02, 12.9) for males; 1.11 (0.98, 1.25) and 1.25 (1.10, 1.42) for females
      respectively), compared with those in the lower level of red meat consumption.
      There was no statistically significant association for consumption of vegetables.
      Consumption of more red meat was suggested to be a factor contributing to body
      weight gain in China. For residents who want to have healthy body weight, it is
      important to consume less red meat in the process of socioeconomic transition.

PMID- 18330399
TI  - Waist circumference, body mass index and health risk factors among middle aged
      Thais.
AB  - Body mass index (BMI) and waist circumference (WC) are important contributors to
      major causes of health risk factors such as high blood cholesterol, high fasting
      blood sugar and high blood pressure. This analysis was designed to assess the
      associations between WC, BMI and each health risk factor in suitable cut-off
      points for WC and BMI among middle aged men and women of Thai population. Cross
      sectional data from the Second National Health Survey in Thailand was analysed.
      This set of data collected by the Ministry of Public Health from 1996 to 1997 was
      obtained from a total of 998 subjects (comprising 396 men and 602 women) aged 45
      50. Results from the Receiver Operating Characteristic curve (ROC curve)
      identified those with health risk factors demonstrating cut-off points for WC
      between 81.5-84 centimeters for men and 76-80.5 centimeters for women and BMI
      between 23.3-23.9 kg/m2 for both genders, respectively. Results from the Multiple
      logistic regression analysis demonstrated lower risks of having high blood
      cholesterol, high fasting blood sugar and high blood pressure with cutoff points
      84 cm for men, 80 cm for women and BMI 23 kg/m2 for both genders compared to cut
      off points 102 cm for men, 88 cm for women and BMI 25 kg/m2 for both genders as
      specified for the population in Western countries. This study has proposed a
      waist circumference of 84 cm (33.6 inches) for middle aged Thai men and 80 cm (32
      inches) for middle aged Thai women and BMI of 23 kg/m2 for both genders.
      Monitoring changes in the waist circumference over time along with BMI may be
      convenient and useful for middle aged Thais to prevent health risk conditions,
      even in the absence of a change in BMI.

PMID- 18330400
TI  - The state of lipid control in patients with diabetes in a public health care
      centre.
AB  - Achieving treatment targets has been difficult in treating diabetic patients.
      This cross-sectional study describes the lipid profiles of patients with diabetes
      mellitus at a public primary health care centre in Sarawak, Malaysia. The targets
      for lipid control were based on the International Diabetes Federation
      recommendation (2002). 1031 patients (98% Type 2 Diabetes) were studied. Fasting
      lipid profiles were available in 990 (96%) patients. The mean total cholesterol
      was 5.3 +/- 1.0 mmol/L, Triglycerides 1.90 +/- 1.26 mmol/L, HDL-C 1.28 +/- 0.33
      mmol/L and LDL-C 3.2 +/- 0.9 mmol/L. Overall, 22% of patients achieved the
      treatment target for LDL-C level < 2.6mmol/L. 67% of patients had HDL-C > 1.1
      mmol/L and 42% of patients had a target TG level below 1.5 mmol/L. Of the 40% of
      patients who received lipid-lowering drug, 17% achieved LDL-C target, 50% had LDL
      C 2.6-4.4 mmol/ L and 33% have LDL-C > 4.0 mmol/L. For the remaining 60% not
      receiving any lipid lowering therapy, 68% had LDL-C between 2.6-4.0 mmol/L and 7%
      had LDL-C level > 4 mmol/L. Dyslipidemia is still under-treated despite the
      availability of effective pharmacological agents and the greatly increased risk
      of cardiovascular diseases in diabetic patients.

PMID- 18330401
TI  - Prevalence of type 2 diabetes and physical activity status in elderly men and
      women from Cyprus (the MEDIS Study).
AB  - Our aim is to investigate the association of being physically active on the
      prevalence of Type 2 diabetes mellitus among elderly people. We enrolled 53 men
      and 97 women, aged 65 to 100, from various areas of Cyprus. Physical activity was
      evaluated through a validated questionnaire (the short International Physical
      Activity Questionnaire, IPAQ). Prevalence of diabetes was 26% in men and 18% in
      women, while 55% of men and 50% of women were reported as being moderately or
      vigorously active. Furthermore, 5% of the participants reported that they smoked,
      4% had stopped smoking, and 8% reported alcohol consumption. People in the upper
      tertile of the IPAQ score were 0.26 times less likely to have diabetes (p <
      0.05); on the other hand people in the lower tertile of the score were 1.7 times
      more likely to have diabetes (p < 0.05). Our findings support the notion of a
      beneficial effect of physical activity on the burden of diabetes in the elderly.

PMID- 18330402
TI  - Relationship between blood lead concentration and nutritional status among Malay
      primary school children in Kuala Lumpur, Malaysia.
AB  - A cross-sectional study was conducted to identify the relationship between blood
      lead concentration and nutritional status among primary school children in Kuala
      Lumpur. A total of 225 Malay students, 113 male and 112 female, aged 6.3 to 9.8
      were selected through a stratified random sampling method. The random blood
      samples were collected and blood lead concentration was measured by a Graphite
      Furnace Atomic Absorption Spectrophotometer. The nutrient intake was determined
      by the 24-hour Dietary Recall method and Food Frequency Questionnaire. An
      anthropometric assessment was reported according to growth indices (z-scores of
      weight-for-age, height-for-age, and weight-for-height). The mean blood lead
      concentration was low (3.4 +/- 1.91 ug/dL) and was significantly different
      between gender. Only 14.7% of the respondents fulfilled the daily energy
      requirement. The protein and iron intakes were adequate for a majority of the
      children. However, 34.7% of the total children showed inadequate intake of
      calcium. The energy, protein, fat and carbohydrate intakes were significantly
      different by gender, that is, males had better intake than females. Majority of
      respondents had normal mean z-score of growth indices. Ten percent of the
      respondents were underweight, 2.8% wasted and 5.4% stunted. Multiple linear
      regression showed inverse significant relationships between blood lead
      concentration with children's age (beta = -0.647, p < 0.001) and per capita
      income (beta = -0.001, p = 0.018). There were inverse significant relationships
      between blood lead concentration with children's age (beta = -0.877, p = 0.001)
      and calcium intake (beta = -0.011, p = 0.014) and positive significant
      relationship with weight-for-height (beta = 0.326, p = 0.041) among those with
      inadequate calcium intake. Among children with inadequate energy intake,
      children's age (beta = -0.621, p < 0.001), per capita income (beta = -0.001, p =
      0.025) and protein intake (beta = -0.019, p = 0.027) were inversely and
      significantly related with blood lead concentration. In conclusion, nutritional
      status might affect the children's absorption of lead and further investigation
      is required for confirmation.

PMID- 18330403
TI  - Antenatal care provided and its quality in field clinics in Gampaha District, Sri
      Lanka.
AB  - A descriptive cross-sectional study was carried out in the Gampaha District in
      Sri Lanka to assess the quality of care provided at antenatal field clinics.
      Checklists were used to assess the structure and process attributes of quality.
      An interviewer administered questionnaire assessed the quality of information
      provided to the clients and client satisfaction. The findings indicated that
      several resource components need upgrading in the district. The majority of
      clinics did not have adequate seating arrangements, lacked a footstool, a height
      measuring instrument and Vitamin C. Less than 50% of the staff were present at
      8.00 a.m. in eight clinics. Health education material was substandard in nine
      clinics. No supervisory notes were made during the preceding year in fourteen
      clinics. Testing urine for sugar and albumin was substandard in 11 and eight
      clinics, respectively. Physical examination of pregnant females was substandard
      in all 20 clinics. No information was provided on some routine procedures carried
      out at the clinic such as blood pressure monitoring, weight gain and vaccines
      given. Client satisfaction exceeded 95% in all aspects except building and
      infrastructure and time spent at the clinic.

PMID- 18330404
TI  - The views of older Malaysians on advanced directive and advanced care planning: a
      qualitative study.
AB  - The provision of optimum care for the ageing population is dependent on the
      understanding of their views and values on end of life issues. A qualitative
      descriptive study was conducted to describe views of elderly Malaysians on
      Advanced Care Planning (henceforth ACP) and Advanced Directives (henceforth AD),
      and explore factors influencing these views. Fifteen elderly subjects with ages
      ranging from 65 to 83 years, representing different ethnic and religious groups
      in Malaysia were selected for in-depth interviews guided by a questionnaire. Five
      core themes were extracted from the interviews: 1) Considering the future 2)
      Contingency plans for future illnesses 3) Attitudes towards life prolonging
      treatment procedures 4) Doctor-patient relationships and 5) Influence of religion
      on decisions related to future illness. Despite the lack of knowledge on ACP and
      AD, older respondents were very receptive to their concept. Although the majority
      agreed on the importance of planning for future medical management and having
      open discussion on end of life issues with their doctor, they felt it unnecessary
      to make a formal written AD. Most felt that the future was best left to fate or
      God, and none had made any contingency plan for severe future illnesses citing
      religion as reason for this view. Cardiopulmonary resuscitation, mechanical
      ventilation and dialysis were considered by most to be invasive life prolonging
      treatments. We suggest that doctors initiate discussions on end of life care with
      every older patient and their family so as to promote awareness and introduce the
      concept of ACP/AD to a Malaysian setting.

PMID- 18330405
TI  - Self-reported cognitive ability and global cognitive performance in adults with
      HIV.
AB  - Although adults with HIV are at risk of developing cognitive impairments, the
      literature suggests that nurses and clinicians should be cautious about relying
      on patients' perceptions of their mental abilities. However, these findings are
      based on a questionnaire of cognitive complaints that may not lend itself easily
      to a clinical setting. In this pilot study, the relationship between a single
      item of self-reported cognitive ability and a global cognitive performance
      composite based on 7 neuropsychological tests was examined in 50 adults with HIV.
      Depressive symptomatology predicted lower self-reported cognitive ability;
      however, lower self-reported cognitive ability was also related to poorer
      cognitive performance but to a lesser extent. These results suggest that adults
      with HIV who report their cognitive ability as being poor may be experiencing
      depression, but they may also be experiencing declines in cognitive performance.
      These findings also suggest that a single item of self-reported cognitive ability
      may have some clinical value in detecting problems with global cognitive
      performance, as well as depression. Interventions for assessing patients and
      improving mood or cognition can be considered by nursing professionals treating
      individuals with HIV who report their cognitive ability as poor.

PMID- 18330406
TI  - Osteoprotective knowledge in a multiethnic epilepsy population.
AB  - Antiepileptic drugs (AEDs) are known to cause bone loss. People with epilepsy
      have twice the fracture rate of nonepilepsy populations. Osteoprotective
      knowledge related to calcium and exercise has not been assessed in people with
      epilepsy. The Osteoporosis Knowledge Test (OKT), a validated, 24-item test, was
      administered to 94 epilepsy patients (28 males and 66 females) to measure
      knowledge of risk factors for osteoporosis and strategies for prevention related
      to calcium and exercise. The mean age of participants was 45 years with an
      average AED exposure of 20 years. Fifty participants were Caucasian and 44 were
      non-Caucasian. No significant differences related to age or gender for the OKT
      were found. One-way analysis of variance (ANOVA) of ethnicity showed that non
      Caucasians had much lower calcium (F = 8.15, p = .005) and exercise (F = 7.71, p
      = .007) knowledge. The total mean OKT score was 11.71 (4.92), reflecting a
      correct response rate of 49%. In previous studies of nonepilepsy populations, the
      mean OKT score ranged from 7.83 to 21.8, with a correct response ranging from
      32.9% to 90.8%. Independent t tests of the individual OKT questions revealed
      specific knowledge deficiencies in the areas of risk factors, exercise, and
      reasons for calcium supplementation for non-Caucasians. Results of this study
      reveal that people with epilepsy, who are at greater risk for metabolic bone
      loss, have lower knowledge scores for calcium and exercise than nonepilepsy
      populations of various ages and genders. Culturally relevantepilepsy materials
      and programs may improve knowledge and adoption of preventative behavior.

PMID- 18330407
TI  - Assessment of caregiver burden in families of persons with multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic, unpredictable, progressive, disabling
      disease. It is generally diagnosed in young adult females between the ages of 20
      and 40 years. Symptoms of MS may include profound fatigue, depression, gait
      disorder, spasticity, blurred vision, and bladder and bowel problems. It is an
      unpredictable disease and has the potential to create a stressful family life.
      Because MS is frequently diagnosed in early adulthood, it may affect
      developmental experiences such as raising a family and building and sustaining a
      career. Satisfaction with relationships can also be altered. MS has a significant
      social, psychological, and physical impact on the affected individual as well as
      his or her family. Partners of people with MS often become caregivers, adding to
      the demands and challenges of family life. As the individual's disease
      progresses, the capacity for self-care may decrease, and the individual may
      require daily assistance from family members. However, the daily assistance that
      family members provide to a disabled spouse, parent, partner, or child can take a
      physical and economic toll on the caregiver, causing caregiver burden. Caregiver
      burden is a multidimensional response to physical, psychological, emotional,
      social, and financial stressors associated with the caregiving experience.
      Caregivers who experience burden are more likely to have a higher risk of
      depression and a lower quality of life. Early recognition of caregiver burden is
      important in determining appropriate interventions.

PMID- 18330408
TI  - The multiple benefits of minimally invasive spinal surgery: results comparing
      transforaminal lumbar interbody fusion and posterior lumbar fusion.
AB  - Minimally invasive transforaminal lumbar interbody fusion (TLIF) offers
      equivalent postoperative fusion rates compared to posterior lumbar fusion (PLF)
      and minimizes the amount of iatrogenic injury to the spinal muscles. The
      objective of this study was to examine the difference in pain perception, stress,
      mood disturbance, quality of life, and immunological indices throughout the
      perioperative course among patients undergoing TLIF and PLF. A prospective,
      nonrandomized descriptive design was used to evaluate these measures among
      patients undergoing TLIF (n = 17) or PLF (n = 18) at 1 week prior to surgery
      (T1), the day of surgery (T2), 24 hours postoperatively (T3), and 6 weeks
      postoperatively (T4). Among TLIF patients, pain, stress, fatigue, and mood
      disturbance were significantly decreased at the 6-week followup visit (T4)
      compared to patients who underwent PLF. The TLIF group also demonstrated
      significantly higher levels (near baseline) of CD8 cells at T4 than the PLF
      group. Interleukin-6 levels were significantly higher in the TLIF group as well,
      which may be an indicator of ongoing nerve regeneration and healing. Knowledge
      concerning the effect of pain and the psychological experience on immunity among
      individuals undergoing spinal fusion can help nurses tailor interventions to
      improve outcomes, regardless of the approach used.

PMID- 18330409
TI  - Factor structure and reliability of the brain impairment behavior scale.
AB  - Stroke is a leading cause of adult disability because of its physical and
      cognitive consequences. Cognitive changes are important contributors to family
      caregivers' experiences of emotional distress. To date, measures to assess
      cognition treat it as a global construct, but it is more likely that unique
      domains differentially affect family caregivers. The research objectives in this
      study were to: (1) identify the different domains of cognitive changes in the
      form of behavioral and psychological symptoms after stroke, and (2) establish the
      reliability of the Brain Impairment Behavior Scale (BIBS) in measuring cognitive
      domains. Family caregivers of stroke survivors (N = 300) completed the BIBS as
      part of cross-sectional and longitudinal studies. A subsample of caregivers
      completed the BIBS twice, 2 weeks apart, to examine the scale's test-retest
      reliability. We used exploratory factor analysis to identify four domains of
      behavioral and psychological symptoms in the BIBS: apathy, depression/emotional
      distress, comprehension/memory problems, and irritability. Internal consistency
      for the subscales representing each identified domain ranged from .78 to .91, and
      the 2-week intra-class correlation coefficients ranged from .75 to .88. Future
      research and clinical use of this measure will increase our understanding of how
      specific domains of stroke survivors' behavioral and psychological symptoms
      affect the well-being of family caregivers.

PMID- 18330410
TI  - Emotional support, physical help, and health of caregivers of stroke survivors.
AB  - Guided by Orem's self-care deficit nursing theory, the purpose of this
      descriptive comparative study was to examine the emotional support, physical
      help, and health of caregivers of stroke survivors. Seventy-three caregivers from
      the Midwest participated in a parent study that examined their experience of
      caring during the first 12 months after stroke. Caregivers were randomized to an
      online intervention of support and education (n = 36 Web users) or a control
      group (n = 37 non-Web users). A secondary analysis of data collected during
      telephone interviews at baseline, 3, 6, and 12 months after stroke was performed.
      No significant mean differences were found between Web and non-Web users in the
      above variables at these points in time. Consequently, the caregivers were merged
      into one group, and the relationships among the variables at the different points
      in time were analyzed. Significant, moderately positive relationships were found
      between emotional support and physical help at baseline, 3, and 12 months. There
      were also significant, moderately positive relationships between emotional
      support and caregiver health at 6 and 12 months. Results highlight the importance
      of caregivers (dependent care agents in Orem's terms) establishing an adequate
      self-care system that provides emotional support and physical help. Findings also
      denote the need for nurses (as caring agents) to assess caregiver health later in
      the caring process and be aware of its relationship to emotional support.

PMID- 18330411
TI  - Pharmacologic management of Alzheimer disease.
AB  - Although the diagnosis of AD can be devastating, treatment options exist that can
      slow the disease's progression and allow patients to continue performing ADLs,
      thereby improving the quality of life for both patient and caregiver. Research is
      ongoing, and it is estimated by the Alzheimer's Association that finding a
      treatment that could delay onset by only 5 years could reduce the number of
      individuals with AD by nearly 50% over the next 50 years (Alzheimer's
      Association, 2007). Although pharmacotherapy is not yet a cure, it does remain an
      important part of a total approach to caring for patients and families affected
      by AD.

PMID- 18330412
TI  - Evolution of nursing research committees.
AB  - Literature and experience recommend that NRCs be clear on their purpose. NRCs
      have a responsibility to educate nurses on the research process and facilitate a
      user-friendly format for proposal review. Communication of research activities,
      including those of the committee, is one way to celebrate success in advancing
      the science of nursing. In the future, NRCs may become more interdisciplinary and
      function within a designated center for nursing research.

PMID- 18330413
TI  - If my syllabus could talk: what would it say about me?

PMID- 18330414
TI  - The certified nurse educator exam: a plan for success.

PMID- 18330415
TI  - Faculty Matters. Mary Spath.

PMID- 18330416
TI  - The successful use of problem-based learning in an online nurse practitioner
      course.
AB  - The development of technology and online education has opened the door to
      creative use of new and existing teaching methodologies. The authors describe how
      they used problem-based learning in an online course as a method for teaching
      clinical decision making to nurse practitioner students. The close match between
      problem-based learning and the characteristics of adult learners and successful
      distance learners is outlined as support for use of this methodology. In
      addition, the authors describe the challenges, rewards, and lessons learned in
      this innovative approach to online education.

PMID- 18330417
TI  - A nursing faculty's transition to teaching online.
AB  - The introduction of web-based instruction into nursing education has resulted in
      a significant change in the responsibilities of nurse educators. This
      phenomenological research study explored the experiences of a graduate nursing
      faculty who had recently made the transition from traditional face-to-face
      instruction to web-based teaching. Through guided interviews, the faculty
      participants provided a rich description of their transition to web-based
      teaching and their perceptions of what faculty members need in order to make such
      a change successfully. Faculty members described how their role as nurse
      educators was reconceptualized as they learned to teach in a different
      environment. The participants' accounts of their experiences revealed a true
      paradigm shift in their perception of the nurse educator role and, for many, a
      comparable shift in their philosophy of teaching.

PMID- 18330418
TI  - Transition from the classroom to the Web: successful strategies for teaching
      online.
AB  - Online courses are an integral part of nursing education programs.The
      responsibility for developing and teaching asynchronous online courses can be
      challenging, especially for neophyte educators. Two experienced educators discuss
      strategies for developing and enhancing selected aspects of asynchronous online
      courses. Practical, evidence-based aspects of designing, conducting, and
      evaluating web-based courses are presented. Examples from courses using WebCT are
      shown.

PMID- 18330419
TI  - Passing the torch: a faculty mentoring program at one school of nursing.
AB  - This article describes a formal mentoring program for new nurse faculty at a
      small, private, midwestern university. Awareness of the shortage of available
      qualified nursing educators, loss of faculty due to retirement, and the desire to
      retain novice faculty prompted the initiation of a mentoring program in a rapidly
      expanding nursing department. Caring concepts from a previously offered "Caring"
      course were integrated into the mentoring program. Personalized attention,
      encouragement, and support and development of a positive attitude toward teaching
      were reported by new faculty in the program and mentor evaluations. Continuation
      of this program and recognition of mentoring as part of a faculty member's
      teaching load demonstrate the Department of Nursing's commitment to this process.

PMID- 18330420
TI  - The Hallmarks Survey: for those who care enough to teach the very best.
AB  - The Hallmarks Survey is based on the 85 indicators recommended by the National
      League for Nursing (NLN) for the Hallmarks of Excellence in Nursing Education.
      With permission from the NLN, graduate students in nursing education developed
      this survey as a holistic and systematic tool for nurse faculty to use for
      assessment of program components. Analysis of data from 53 faculty respondents
      yielded areas of strength and areas for development for each hallmark category.
      Recommendations based on survey findings were disseminated to diverse audiences
      in multiple venues. A follow-up evaluation of the survey was also conducted. The
      Hallmarks Survey provides comprehensive assessment data that faculty may use to
      promote excellence in nursing education.

PMID- 18330421
TI  - Educating nursing students about the dangers of drinking games.
AB  - Alcohol abuse is a serious problem among college students, and drinking games are
      a common, yet risky practice in this population. This article provides a
      description of different types of drinking games along with a discussion of the
      risks of participation, factors that may lead college students to participate,
      interventions that may help reduce student participation, and reasons why nurse
      faculty should consider incorporating information about drinking games into their
      curricula.

PMID- 18330422
TI  - Cultivating healthful work environments in nursing education.

PMID- 18330423
TI  - Characterization of di-, tri-, and tetranucleotide microsatellite markers with
      perfect repeats for Trypanosoma brucei and related species.
AB  - Trypanosoma brucei, unicellular parasites causing human sleeping sickness and
      animal nagana, have a great impact on the socio-economic environment of sub
      Saharan Africa. The dynamics of the parasite are still poorly understood. We have
      characterized 14 polymorphic di-, tri-, and tetranucleotide microsatellite loci
      with perfect repeats (only one motif) exhibiting between 5 and 16 alleles in T.
      brucei isolates from all over Africa and from all described subspecies. The
      microsatellites will be useful in addressing population genetic questions in T.
      brucei to better understand the population structure and spread of this important
      parasite.

PMID- 18330424
TI  - 2007 Annual Meeting American-Hepato-Pancreato-Biliary Association April 19-22,
      2007 Bally's Las Vegas Hotel.

PMID- 18330425
TI  - Seventh Americas Hepatopancreatobiliary Congress ANNUAL SCIENTIFIC SESSION & POST
      GRADUATE PROGRAM April 19-22, 2007 Bally's Hotel Las Vegas, Nevada.

PMID- 18330426
TI  - Are facial nerve outcomes worse following surgery for cystic vestibular
      schwannoma?
AB  - OBJECTIVES: This study sought to determine explicitly whether postsurgical facial
      nerve outcomes for patients with a cystic component to a vestibular schwannoma
      were significantly different from those with a solid tumor. DESIGN: Seventy
      patients who underwent translabyrinthine surgery for a cystic vestibular
      schwannoma between May 1981 and the present, and who had complete records in our
      database, were identified. These were compared with a group of patients with
      solid tumors matched to the study group on the following parameters: House
      Brackmann grade at presentation, tumor size, surgical approach, age. SETTING:
      Regional tertiary referral center. PARTICIPANTS: Adult patients with vestibular
      schwannomas. MAIN OUTCOME MEASURES: House-Brackmann score 2 years following
      surgery. RESULTS: No significant difference was found between the two groups.
      CONCLUSIONS: The perceived difference in outcomes between cystic and solid
      vestibular schwannomas cannot be demonstrated when confounding factors such as
      tumor size are taken into account.

PMID- 18330427
TI  - Microanatomy and surgical approaches to the infratemporal fossa: an anaglyphic
      three-dimensional stereoscopic printing study.
AB  - OBJECTIVE: The infratemporal fossa (ITF) is a continuation of the temporal fossa
      between the internal surface of the zygoma and the external surface of the
      temporal bone and greater wing of the sphenoid bone that is sitting deep to the
      ramus of the mandible. The principal structure to understanding its relationships
      is the lateral pterygoid muscle. Other important structures are the medial
      pterygoid muscle, the maxillary artery, the pterygoid venous plexus, the otic
      ganglion, the chorda tympani nerve and the mandibular nerve. In this study, we
      describe the microsurgical anatomy of the ITF, as viewed by step-by-step
      anatomical dissection and also through the perspective of three lateral
      approaches and one anterior surgical approach. METHODS: Eight cadaver specimens
      were dissected. In one side of all specimens, an anatomical dissection was done
      in which a wide preauricular incision from the neck on the anterior border of the
      sternoclidomastoid muscle at the level of the cricoid cartilage to the superior
      temporal line was made. The flap was displaced anteriorly and the structures of
      the neck were dissected followed by a zygomatic osteotomy and dissection of the
      ITF structures. On the other side were the surgical approaches to the ITF. The
      combined infratemporal and posterior fossa approach was done in two specimens,
      the subtemporal preauricular infratemporal fossa approach in two, the zygomatic
      approach in two, and the lateral transantral maxillotomy in two. The anatomical
      dissections were documented on the three-dimensional (3D) anaglyphic method to
      produce stereoscopic prints. RESULTS: The lateral pterygoid muscle is one of the
      principal structures to enable understanding of the relationships into the ITF.
      The tendon of the temporal muscle inserts in the coronoid process at the ITF. The
      maxillary artery is the terminal branch of the external carotid artery that
      originates at the neck of the mandible and runs into the parotid gland. In our
      dissections the maxillary artery was lateral to the buccal, lingual, and inferior
      alveolar nerves. We found the second part of the maxillary artery superficial to
      the lateral pterygoid muscle in all specimens The anterior and posterior branches
      of the deep temporal artery supply the temporal muscle. In two cases we found a
      middle deep temporal artery. The different approaches that we used provided
      different views of the same anatomical landmarks and this provides not only safer
      surgery but also the best choice to approach the ITF according with the pathology
      extension. CONCLUSIONS: The ITF is a complex region on the skull base that is
      affected by benign and malignant tumors. The study through different routes is
      helpful to disclose the relationship among the anatomical structures. Although
      the authors have shown four approaches, there are a variety of approaches and
      even a combination of these can be used. This type of anatomical knowledge is
      essential to choosing the best approach to treat lesions in this area.

PMID- 18330428
TI  - Frontozygomatic approach to intraorbital tumors.
AB  - We removed 12 intraorbital tumors (5 schwannomas, 3 meningiomas, 2 cavernomas, 1
      pleomorphic adenoma, and 1 neuroblastoma) using the frontozygomatic approach. No
      patients died. Postoperatively, 1 patient developed transient ptosis, and 3
      patients had mild enophthalmos. Two patients with a meningioma developed
      transient worsening of their visual acuity and visual field. The frontozygomatic
      approach for surgical treatment of intraorbital tumors provides a wide visual
      field exposing the entire optic nerve. This approach is indicated for large
      intraorbital tumors, tumors affecting the optic nerve or orbital apex,
      intraorbital tumors that have extended into the intracranial cavity, and
      intracranial tumors that have extended into the orbit. The operative procedure
      for intraorbital tumor is determined by the location of the lesion and by the
      direction of its growth. The procedure is applicable to all intraorbital tumors.
      It reduces discomfort for surgeons while providing a relatively wide surgical
      field.

PMID- 18330429
TI  - Idiopathic temporal bone encephalocele.
AB  - Meningoencephaloceles are herniations of brain tissue through dehiscences of the
      skull base. These skull defects are either acquired (otologic infection, trauma,
      surgery, neoplasia) or spontaneous. Spontaneous temporal bone
      meningoencephaloceles are quite rare conditions, usually congenital in origin
      presenting during childhood, and only occasionally idiopathic presenting during
      adulthood. We present a case of temporal bone meningoencephalocele of adult
      onset. The patient was treated with exploratory mastoidectomy, amputation of the
      herniated cele and closure of the defect with temporalis fascia and an inferiorly
      based pedicled muscular flap. No reconstruction of the bony defect was performed,
      as the layered closure was considered adequate. Twelve months' follow-up revealed
      no relapse of the condition or postoperative complications.

PMID- 18330430
TI  - Trigeminal amyloidoma: case report and review of the literature.
AB  - The authors present a case of amyloid infiltration involving the trigeminal nerve
      that mimicked a malignant cavernous sinus tumor with perineural tumor
      infiltration. A 64-year-old man presented with trigeminal nerve numbness. Imaging
      revealed a plaque-like enhancing lesion along the right lateral cavernous sinus
      extending anteriorly into Meckel's cave and involving the proximal V2 and V3
      branches of the trigeminal nerve. The patient underwent an extradural
      frontotemporal craniotomy with middle fossa exposure of the cavernous sinus to
      diagnose and treat the presumed malignant cavernous sinus tumor. A reddish mass
      involving the lateral dural wall of the cavernous sinus was resected. The
      gasserian ganglion, V2, and V3, the latter of which was biopsied, were enlarged.
      Permanent histopathological studies showed microscopic eosinophilic, amorphous
      material, which stained positive for Congo red, and an absence of neoplastic
      cells. The final diagnosis was amyloidoma. Thus, amyloidomas can involve the
      trigeminal nerve or ganglia and should be considered in the differential
      diagnosis of a cavernous sinus lesion mimicking a tumor. Patients may have
      symptomatic improvement of trigeminal neuropathy with resection of the amyloidoma
      outside the nerve capsule that is compressing the nerve, while resection of the
      lesion from within the capsule may result in permanent trigeminal nerve
      dysfunction.

PMID- 18330431
TI  - Intracranial/Extracranial meningioma arising in the hypoglossal canal: case
      report.
AB  - A case of a patient with a posterior fossa meningioma extending through the
      hypoglossal canal to the cervical region as described in this article has not
      been previously described in the literature. Investigations and surgical
      management are outlined and pathological classifications are discussed. A
      literature review including recent reports of extracranial meningiomas is
      presented. Extracranial meningiomas are exceedingly rare and a high index of
      suspicion is necessary to make the diagnosis.

PMID- 18330432
TI  - Clinical Course and Autopsy Findings of a Patient with Clival Chordoma Who
      Underwent Multiple Surgeries and Radiation during a 10-Year Period.
AB  - The management of clival chordoma remains problematic. We present the case of a
      48-year-old woman with clival chordoma who underwent multiple surgeries and
      radiation therapy, including gamma knife stereotactic radiosurgery (GK-SRS),
      during a 10-year clinical course. The tumor was initially removed by gross total
      resection via the trans-sphenoidal approach, followed by external linac radiation
      therapy. The tumor recurred at the clivus 5 years after the initial operation.
      After repeated trans-sphenoidal removal of recurrent tumors, she twice underwent
      GK-SRS for a tumor remnant adjacent to the brainstem. Although this part of the
      tumor was controlled by GK-SRS, there was further tumor extension toward the
      sphenoid and maxillary sinuses. Ultimately, lower cranial nerve dysfunction
      developed due to tumor extension into the lower part of the clivus and the
      patient died of respiratory failure. Autopsy revealed the tumor to extend from
      the lower clivus to the bilateral middle fossae. The lower part of the tumor
      extended to the nasal cavity and to the posterior wall of the pharynx, resulting
      in compression of the upper pharyngeal region. The tumor around the jugular
      foramen compressed the lower cranial nerves bilaterally. Tumor cells did not,
      however, invade the intradural space microscopically. Although chordoma is not
      biologically malignant, this tumor can show massive extension with destruction of
      bony structures and extracranial invasion of connective tissues. Therefore, the
      optimal treatment strategy is to remove the tumor mass as extensively as
      possible, including normal bony structures and connective tissues surrounding the
      tumor, using skull base surgical techniques.

PMID- 18330433
TI  - Endoscopic-Assisted Removal of Orbital Roof Lesions via a Skin Crease Approach.
AB  - OBJECTIVE: To describe the technique and indications for an endoscopic-assisted
      approach to orbital roof lesions. MATERIALS AND METHODS: The technique was used
      for six cases of orbital roof lesions. An anterior orbitotomy was performed via
      an upper eyelid skin crease incision. Areas of the lesion behind the superior
      orbital rim or abutting the dura were removed with the aid of a rigid Storz 3
      chip video-endoscope with 30-, 45-, or 70-degree tip. RESULTS: Six patients with
      lesions involving the orbital roof were treated using endoscopic-assisted
      curettage. There were five males and one female with a mean age of 39.6 years
      (range, 5 months to 67 years). There were two cases each of cholesterol
      granuloma, Langerhans' cell histiocytosis, and orbital dermoid. The lesions were
      successfully removed in all cases with a good outcome. Average follow-up was 2.6
      years; range, 6 months to 5 years. CONCLUSION: This technique may be suitable for
      selected erosive lesions of the superior orbit involving the orbital roof.

PMID- 18330434
TI  - Pituitary adenoma associated with intraventricular meningioma: case report.
AB  - Although rare, the association of intracranial meningiomas and pituitary adenomas
      has been reported. Intraventricular meningiomas are unusual, and meningiomas
      located in the fourth ventricle are even more so. We report a patient who
      harbored a prolactin-secreting pituitary adenoma and a fourth ventricle
      meningioma who was treated with surgical resection of the latter and medical
      treatment for the former. To our knowledge, this is the first report of such an
      unusual association.

PMID- 18330435
TI  - Advocacy for eye health.

PMID- 18330436
TI  - Turning fine words into action: suggestions for high-level advocacy.

PMID- 18330437
TI  - The challenges of advocacy in sub-Saharan Africa.

PMID- 18330438
TI  - Convincing governments to act: VISION 2020 and the Millennium Development Goals.

PMID- 18330439
TI  - Charting new frontiers of hope in Pakistan.

PMID- 18330440
TI  - Advocacy to improve the delivery of eye care.

PMID- 18330441
TI  - Improving gender equity in eye care: advocating for the needs of women.

PMID- 18330443
TI  - RAAB survey of Pemba and Unguja islands, Zanzibar.

PMID- 18330442
TI  - The 'ngisipet' and trachoma prevention: solving the latrine problem in nomadic
      tribes.

PMID- 18330444
TI  - Poor vision and barriers to treatment among commercial vehicle drivers in Plateau
      State, Nigeria.

PMID- 18330445
TI  - Analysis of eye care services in South Africa's public sector.

PMID- 18330446
TI  - Evaluating the role of Anganwadi workers as key informants to identify blind
      children in Pune, India.

PMID- 18330447
TI  - Causes of childhood blindness and available services in schools for the disabled
      in southern Viet Nam.

PMID- 18330448
TI  - The characteristics of patients presenting with advanced proliferative diabetic
      retinopathy in Shanxi Eye Hospital, China.

PMID- 18330449
TI  - The prevalence of presbyopia and the feasibility of community distribution of
      near spectacles in adults in Zanzibar, East Africa.

PMID- 18330450
TI  - How to measure intraocular pressure: applanation tonometry.

PMID- 18330451
TI  - Million-dollar advocacy success for VISION 2020 Australia.

PMID- 18330453
TI  - Useful resources for advocacy.

PMID- 18330452
TI  - Better vision for safer roads: an instance of accidental advocacy in Nigeria.

PMID- 18330454
TI  - Do antidepressants really work?

PMID- 18330455
TI  - Reduced subgenual cingulate volumes in mood disorders: a meta-analysis.
AB  - OBJECTIVE: Converging evidence suggests that the subgenual cingulate (SGC) is
      implicated in regulation of mood and in the pathophysiology of mood disorders.
      Our objective was to carry out the first meta-analysis of SGC volumes in patients
      with mood disorders. METHODS: We reviewed 10 volumetric magnetic resonance
      imaging studies of SGC volumes in patients with unipolar depression and bipolar
      disorders. For meta-analysis, we used standardized differences between means
      (SDMs) and random effects models. In the search for sources of heterogeneity, we
      subdivided the studies on the basis of diagnosis and presence of family history.
      RESULTS: The volumes of left and right SGC in patients with mood disorders were
      significantly reduced relative to healthy control subjects (SDM -0.38, 95%
      confidence interval [CI] -0.67 to -0.1 and SDM -0.2, 95% CI -0.4 to -0.007,
      respectively). There were significant SGC volume reductions in patients with
      unipolar (left SGC SDM -0.5, 95% CI -0.92 to -0.07; right SGC SDM -0.33, 95% CI 
      0.64 to -0.02,), but not bipolar, disorder. Patients with a positive family
      history of mood disorders showed significant left SGC volume decrease (SDM -0.52,
      95% CI -0.96 to -0.07), which was not present among subjects without family
      history of mood disorders. There was no association between age and SGC volumes.
      CONCLUSION: The available evidence suggests the existence of left and less robust
      right SGC volumetric reductions in patients with mood disorders, predominantly in
      those with unipolar depression. The effect size of this difference was moderate
      and increased in more homogeneous subgroups of patients with a positive family
      history. The clustering of SGC abnormalities in patients with a family history,
      their presence early in the illness course and their lack of progression with age
      make SGC a candidate for a primary vulnerability marker, although studies in
      unaffected high-risk subjects are missing.

PMID- 18330456
TI  - Implication of the polyamine system in mental disorders.
AB  - The polyamine pathway has an essential role in many cellular functions and has
      been implicated in several pathological conditions. Accumulating evidence
      suggests that the polyamine system also plays a role in the etiology and
      pathology of mental disorders. Alterations in the expression and activity of
      polyamine metabolic enzymes, as well as changes in the levels of the individual
      polyamines, have been observed in multiple conditions, including schizophrenia,
      mood disorders, anxiety and suicidal behaviour. Additionally, these components
      have been found to be altered by various psychiatric treatments. Further, the
      polyamines and their precursors have demonstrated both antidepressant and
      anxiolytic effects. Overall, findings to date suggest that the polyamine pathway
      represents an important frontier for the development of neuropharmacological
      treatments.

PMID- 18330457
TI  - The auditory-visual integration of anger is impaired in alcoholism: an event
      related potentials study.
AB  - OBJECTIVES: Chronic alcoholism leads to impaired visual and auditory processing
      of emotions, but the cross-modal (auditory-visual) processing of emotional
      stimuli has not yet been explored. Our objectives were to describe the
      electrophysiological correlates of unimodal (visual and auditory) impairments in
      emotion processing in people suffering from alcoholism, to determine whether this
      deficit is general or emotion-specific, and to explore potential deterioration in
      the specific cross-modal integration processes in alcoholism. METHODS: We used an
      emotion-detection task, with recording of event-related potentials (ERPs), in
      which 15 patients suffering from alcoholism and 15 matched healthy control
      subjects were asked to detect the emotion (angry, happy or neutral) displayed by
      auditory, visual or auditory-visual stimuli. Behavioural performance and ERP data
      recorded between June 2005 and April 2006 were analyzed. RESULTS: ERPs
      demonstrated that the deficit in alcoholism originates earlier in the cognitive
      stream than has previously been described (mainly P300), namely, at the level of
      specific face (N170) and voice (N2) perceptive processing. Moreover, while
      patients with alcoholism did not show impaired processing of happy and neutral
      audio-visual stimuli, they did have a specific impairment in the cross-modal
      processing of anger. A source location analysis was used to confirm and
      illustrate the results. CONCLUSION: These results suggest that the specific
      deficit that people with alcoholism demonstrate in processing anger stimuli,
      widely described in clinical situations but not clearly identified in earlier
      studies (using unimodal stimuli), is particularly obvious during cross-modal
      processing, which is more common than unimodal processing in everyday life.

PMID- 18330458
TI  - Serotonin transporter genotype interacts with paroxetine plasma levels to
      influence depression treatment response in geriatric patients.
AB  - OBJECTIVE: To investigate whether variable antidepressant response may be
      influenced by an interaction between the serotonin transporter promoter
      polymorphism (5-HTTLPR) and antidepressant concentration. METHODS: Elderly
      subjects with depression treated with paroxetine (n = 110) were genotyped and
      assessed with the Hamilton Rating Scale for Depression (HAMD). A mixed-effect
      analysis of repeated measures was used. RESULTS: There was an interaction between
      early paroxetine concentration and 5-HTTLPR genotype on symptomatic improvement
      over 12 weeks (F(18,59.5) = 1.8, p < 0.05), as well as main effects of both
      paroxetine concentration (F(68,55.3) = 2.4, p < 0.005) and genotype (F(2,74.2) =
      5.7, p < 0.005). Paroxetine concentrations were correlated with change in HAMD
      scores after 2 weeks of treatment in subjects with the short (s) allele (r =
      0.31, p < 0.05) but not in subjects homozygous for the long (l) allele.
      CONCLUSION: The results demonstrate a concentration-response relation for
      paroxetine in late-life depression and support the hypothesis for both a direct
      main effect and a moderating influence of 5-HTTLPR alleles on this concentration
      response relation.

PMID- 18330459
TI  - Serotonin receptor subtype and p11 mRNA expression in stress-relevant brain
      regions of suicide and control subjects.
AB  - OBJECTIVE: Studies comparing people suffering from depression who committed
      suicide with control subjects have yielded inconsistent results regarding
      serotonin (5-HT) involvement in pathology, possibly owing to procedural factors.
      Our objective was to investigate which 5-HT receptor subtypes might be associated
      with depression and suicide, whether receptor differences vary across brain
      regions and whether they are moderated by sex. METHODS: We assessed messenger
      ribonucleic acid (mRNA) expression of several 5-HT receptor subtypes and that of
      p11, a protein involved in the functional expression of 5-HT(1B), in several
      stress-relevant brain regions. Tissue was obtained soon after death, and RNA
      integrity and pH was confirmed to be appropriate. Brain tissue from suicide
      subjects suffering from depression and from control subjects who had died from
      other causes (10 men and 10 women in each condition) was obtained within 6.5
      hours postmortem. Quantitative polymerase chain reaction analyses determined mRNA
      expression of 5-HT receptor subtypes and p11 within the frontopolar cortex,
      orbitofrontal cortex, hippocampus, amygdala and paraventricular nucleus. The 5-HT
      transporter (5-HTT) was also assessed in the raphe nucleus. RESULTS: Differences
      of 5-HT(1A), 5-HT(1B) and p11 mRNA expression between people who committed
      suicide and control subjects were relatively widespread, whereas 5-HT(2A) and 5
      HT(2C) variations were restricted to the frontopolar cortex and amygdala. Within
      the dorsal raphe nucleus, neither 5-HT(1A) nor 5-HTT mRNA expression differed
      between those who committed suicide and control subjects. CONCLUSION: Several 5
      HT receptor subtypes are associated with depression and suicide, but these
      receptor differences vary across brain regions and are moderated by sex.

PMID- 18330460
TI  - Rostral anterior cingulate volume predicts treatment response to cognitive
      behavioural therapy for posttraumatic stress disorder.
AB  - OBJECTIVE: To index the extent to which treatment response in posttraumatic
      stress disorder (PTSD) is predicted by rostral anterior cingulate cortex (rACC)
      volume. METHOD: We used structural magnetic resonance imaging in a 1.5 T scanner
      to examine subjects with PTSD (n = 13), traumatized control subjects (n = 13) and
      nontraumatized control subjects (n = 13). Subjects with PTSD then participated in
      8 sessions of cognitive-behavioural therapy, after which we reassessed them for
      PTSD. RESULTS: According to voxel-based morphometry, treatment responders had
      larger rACC volume than nonresponders. Further, symptom reduction was associated
      with larger rACC volume. CONCLUSION: Consistent with evidence for the neural
      bases of extinction learning, PTSD patients with larger rACC volume may be better
      able to regulate fear during cognitive-behavioural therapy and thus achieve
      greater treatment gains.

PMID- 18330461
TI  - Combined antidepressants and CBT for panic disorder with agoraphobia.

PMID- 18330462
TI  - Postictal psychosis: common, dangerous, and treatable.
AB  - Postical psychosis often complicates chronic epilepsy, especially in patients
      with seizure clusters that include tonic-clonic seizures, bilateral cerebral
      dysfunction (e.g., bilateral epileptiform activity or history of encephalitis),
      and a family history of psychiatric illness. Psychosis includes delusions,
      auditory and visual hallucinations, mood changes, and aggressive behavior. It
      typically emerges after a lucid interval of hours or days after the last seizure.
      This treatable disorder is associated with serious morbidity and mortality.

PMID- 18330463
TI  - Vagus nerve stimulation for generalized epilepsy?...Show me the evidence!

PMID- 18330464
TI  - Channeling into the epilepsies.

PMID- 18330465
TI  - Multiple auras: not an ominous sign for epilepsy surgery.

PMID- 18330466
TI  - Suicide in patients with epilepsy.

PMID- 18330467
TI  - The ups and downs of hippocampal metabotropic glutamate receptors: ramifications
      for epileptogenesis and cognitive impairment following status epilepticus.

PMID- 18330468
TI  - Epileptogenic role of astrocyte dysfunction.

PMID- 18330469
TI  - Antiepileptic drug transport--of mice and men.

PMID- 18330470
TI  - Altered neuronal chloride homeostasis and excitatory GABAergic signaling in human
      temporal lobe epilepsy.

PMID- 18330472
TI  - Catalytic mechanisms, basic roles, and biotechnological and environmental
      significance of halogenating enzymes.
AB  - The understanding of enzymatic incorporation of halogen atoms into organic
      molecules has increased during the last few years. Two novel types of
      halogenating enzymes, flavin-dependent halogenases and alpha-ketoglutarate
      dependent halogenases, are now known to play a significant role in enzyme
      catalyzed halogenation. The recent advances on the halogenating enzymes RebH,
      SyrB2, and CytC3 have suggested some new mechanisms for enzymatic halogenations.
      This review concentrates on the occurrence, catalytic mechanisms, and
      biotechnological applications of the halogenating enzymes that are currently
      known.

PMID- 18330473
TI  - Class I phosphatidylinositol 3-kinase inhibitor LY294002 activates autophagy and
      induces apoptosis through p53 pathway in gastric cancer cell line SGC7901.
AB  - We aimed to study the effects of LY294002, an inhibitor of class I
      phosphatidylinositol 3-kinase (PI3K), on proliferation, apoptosis, and autophagy
      in gastric cancer cell line SGC7901. In this study, we showed that LY294002
      inhibited the viability of gastric cancer SGC7901 cells. We also showed that
      LY294002 increased the expression of microtubule-associated protein 1 light chain
      3 (LC3), and increased monodansylcadaverine (MDC)-labeled vesicles. LY294002
      activated autophagy by activating p53 and caspase-3, and induced apoptosis by up
      regulating p53 and p53-up-regulated modulator of apoptosis (PUMA). Therefore,
      LY294002 might induce cytotoxicity in SGC7901 cells through activation of p53 and
      the downstream point PUMA. These findings suggest that inhibition of the class I
      PI3K signaling pathway is a potential strategy for managing gastric cancers.

PMID- 18330474
TI  - Fate and protective effect of marrow stromal cells after subretinal
      transplantation.
AB  - Engraftment of marrow stromal cells (MSCs) has been proposed as a therapeutic
      approach for degenerative diseases. In this study we investigated the fate and
      dynamic progress of grafted MSCs in living retina with the aim of evaluating the
      use of transplanted MSCs to treat retinal degeneration. Approximately 1x10(5) gfp
      MSCs in 2 microl phosphate-buffered saline were injected into the subretinal
      space of adult Sprague-Dawley rats. Two weeks later, approximately 0.174%+/
      0.082% of the transplanted cells had survived and diffused into the subretinal
      space. Nine weeks after transplantation the surviving gfp-MSCs accounted for
      0.049%+/-0.023% of the number of cells injected and were mainly located at the
      injection site. The same number of MSCs were transplanted into the left eye
      subretinal space of 3-week-old hereditary retinal degenerative Royal College of
      Surgeons rats, and phosphate-buffered saline was injected into their right eyes
      as a control. Five weeks after transplantation, the amount of rudimentary
      photoreceptors was more significantly increased in grafted eyes than in control
      eyes. The results indicated that grafted MSCs could survive and rescue retinal
      degeneration.

PMID- 18330475
TI  - Cloning and characterization of a heat shock protein 70 gene, MsHSP70-1, in
      Medicago sativa.
AB  - Some members of the heat shock protein 70 (HSP70) family have important functions
      in organism development. Here, we identified an alfalfa (Medicago sativa L. cv.
      Algonquin) HSP70 gene, MsHSP70-1, using cDNA array and reverse transcription
      polymerase chain reaction. This gene contains a 1947 bp open reading frame
      encoding a protein of 649 amino acids. This protein contains all conserved
      domains, motifs, and characteristic sequences of plant HSP70s. The expression of
      MsHSP70-1 is enhanced in nodule compared with root, stem, leaf, and flower, and
      throughout the process of nodule development. Northern hybridization analysis
      indicated that the expression of MsHSP70-1 in nodule requires the active bacA
      gene of rhizobia. These results suggested that MsHSP70-1 might play an important
      role in alfalfa nodule development.

PMID- 18330476
TI  - Identification and characterization of a novel peptide ligand of Tie2 for
      targeting gene therapy.
AB  - Tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2
      (Tie2) has been considered as a rational target for gene therapy in solid tumors.
      In order to identify a novel peptide ligand of Tie2 for targeted gene therapy, we
      screened a phage display peptide library and identified a candidate peptide
      ligand NSLSNASEFRAPY (designated GA5). Binding assays and Scatchard analysis
      revealed that GA5 could specifically bind to Tie2 with a dissociation constant of
      2.1x10(-8)M. In addition, we showed that GA5 was internalized into tumor cells
      highly expressing Tie2. In the biodistribution assay, (125)I-GA5 was mainly
      accumulated in SPC-A1 xenograft tumors that express Tie2. In gene delivery
      studies, GA5-conjugated polyethylenimine vector could achieve greater transgene
      transduction than non-targeted vectors both in vitro and in vivo. Tumor growth
      inhibition was observed in SPC-A1 xenograft-bearing mice that received eight
      intratumoral injections of GA5-polyethylenimine/p53 complexes in 3 weeks. The
      difference in tumor volume between the experiment and control groups was
      significant (P<0.05). Our results showed that GA5 is a potentially efficient
      targeting element for cancer gene or molecular therapy.

PMID- 18330477
TI  - Free cholesterol-induced macrophage apoptosis is mediated by inositol-requiring
      enzyme 1 alpha-regulated activation of Jun N-terminal kinase.
AB  - Macrophage death in advanced atherosclerotic lesions leads to lesional necrosis,
      possible plaque rupture, and acute vascular occlusion. A likely cause of
      macrophage death is the accumulation of free cholesterol (FC) leading to
      activation of endoplasmic reticulum (ER) stress-induced apoptosis. Inositol
      requiring enzyme 1 alpha (IRE1alpha) is an integral membrane protein of the ER
      that is a key signaling step in cholesterol-induced apoptosis in macrophages,
      activated by stress in the ER. However, the role of IRE1alpha in the regulation
      of ER stress-induced macrophage death and the mechanism for this process are
      largely unclear. In this study, a cell culture model was used to explore the
      mechanisms involved in the ER stress pathway of FC-induced macrophage death. The
      results herein showed that FC loading of macrophages leads to an apoptotic
      response that is partially dependent on initiation by activation of IRE1alpha.
      Taken together, these results showed that the IRE1-apoptosis-signaling kinase 1-c
      Jun NH2-terminal kinase cascade pathway was required in this process. Moreover,
      the data suggested a novel cellular mechanism for cholesterol-induced macrophage
      death in advanced atherosclerotic lesions. The critical function of this
      signaling cascade is indicated by prevention of ER stress-induced apoptosis after
      inhibition of IRE1alpha, or c-Jun NH2-terminal kinase.

PMID- 18330478
TI  - Role of ornithine decarboxylase in breast cancer.
AB  - Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis
      that decarboxylates ornithine to putrescine, has become a promising target for
      cancer research. The aim of this study is to investigate the role of ODC in
      breast cancer. We detected expression of ODC in breast cancer tissues and four
      breast cancer cell lines, and transfected breast cancer cells with an adenoviral
      vector carrying antisense ODC (rAd-ODC/Ex3as) and examined their growth and
      migration. ODC was overexpressed in breast cancer tissues and cell lines compared
      with non-tumor tissues and normal breast epithelial cells, and there was a
      positive correlation between the level of ODC mRNA and the staging of tumors. The
      expression of ODC correlated with cyclin D1, a cell cycle protein, in
      synchronized breast cancer MDA-MB-231 cells. Gene transfection of rAd-ODC/Ex3as
      markedly down-regulated expression of ODC and cyclin D1, resulting in suppression
      of proliferation and cell cycle arrest at G0-G1 phase, and the inhibition of
      colony formation, an anchorage-independent growth pattern, and the migratory
      ability of MDA-MB-231 cells. rAd-ODC/Ex3as also markedly reduced the
      concentration of putrescine, but not spermidine or spermine, in MDA-MB-231 cells.
      The results suggested that the ODC gene might act as a prognostic factor for
      breast cancer and it could be a promising therapeutic target.

PMID- 18330479
TI  - Cloning and expression pattern of a Smad3 homolog from the pearl oyster, Pinctada
      fucata.
AB  - Several transforming growth factor beta (TGFbeta) superfamily members have been
      identified from mollusks. The significant effects of TGFbeta signaling pathways
      on bone formation in vertebrates give clues to the signal transduction mechanism
      and how the shell of oysters is formed. However, what kinds of mediators are
      involved in the molluscan TGFbeta signaling pathways, and how they play their
      functions in mollusks has not been well explained due to a lack of genomic
      information and the failure to establish oyster cell lines. That is, if we knew
      the genome sequence we could search the TGFbeta superfamily members using the
      blast program (http://www.ncbi.nlm.nih.gov/), and if we established the molluscan
      cell line, we could transfect the gene of interest to the cell and detect its
      influence on expression levels of other genes, such as the matrix proteins.
      Therefore, to investigate whether there are similar TGFbeta pathways in mollusks,
      many important mediators should be identified. In this paper, we report a cDNA
      encoding a Smad3 homolog (designated Pf-Smad3) that was isolated from the pearl
      oyster, Pinctada fucata. Sequence alignment showed that Pf-Smad3 contains a DNA
      binding MH1 domain and a Runx2/Cbfa1-binding MH2 domain, and shares an extremely
      high similarity with Smad3 proteins in vertebrates. However, Smad proteins in
      Drosophila and Caenorhabditis elegans are very different from other Smad3
      proteins. Reverse transcription-polymerase chain reaction results indicated that
      Pf-Smad3 mRNA was expressed ubiquitously in adult Pin. fucata and was expressed
      at different levels at different developmental stages. In situ hybridization
      results showed that Pf-Smad3 mRNA was expressed mainly at the outer epithelial
      cells of the middle fold and the inner epithelial cells of the outer fold,
      especially around the gutter. These results suggested that Pf-Smad3 might take
      part in many physiological processes, including biomineralization, in oysters.

PMID- 18330480
TI  - Germ cell nuclear factor directly represses the transcription of peroxisome
      proliferator-activated receptor delta gene.
AB  - Germ cell nuclear factor (GCNF) is a transcription factor that can repress gene
      transcription and plays an important role during spermatogenesis. Peroxisome
      proliferator-activated receptor delta (PPARdelta) is a nuclear hormone receptor
      belonging to the steroid receptor superfamily. It can activate the expression of
      many genes, including those involved in lipid metabolism. In this report, we
      showed that GCNF specifically interacts with PPARdelta promoter. Overexpression
      of GCNF in African green monkey SV40-transformed kidney fibroblast COS7 cells and
      mouse embryo fibroblast NIH 3T3 cells represses the activity of PPARdelta
      promoter. The mutation of GCNF response element in PPARdelta promoter relieves
      the repression in NIH 3T3 cells and mouse testis. Moreover, we showed that GCNF
      in nuclear extracts of mouse testis is able to bind to PPARdelta promoter
      directly. We also found that GCNF and PPARdelta mRNA were expressed with
      different patterns in mouse testis by in situ hybridization. These results
      suggested that GCNF might be a negative regulator of PPARdelta gene expression
      through its direct interaction with PPARdelta promoter in mouse testis.

PMID- 18330481
TI  - Synthetic liver X receptor agonist T0901317 inhibits semicarbazide-sensitive
      amine oxidase gene expression and activity in apolipoprotein E knockout mice.
AB  - Semicarbazide-sensitive amine oxidase (SSAO) catalyzes oxidative deamination of
      primary aromatic and aliphatic amines. Increased SSAO activity has been found in
      atherosclerosis and diabetes mellitus. We hypothesize that the anti-atherogenic
      effect of liver X receptors (LXRs) might be related to the inhibition of SSAO
      gene expression and its activity. In this study, we investigated the effect of
      LXR agonist T0901317 on SSAO gene expression and its activity in apolipoprotein E
      knockout (apoE(-/-)) mice. Male apoE(-/-) mice (8 weeks old) were randomly
      divided into four groups: basal control group; vehicle group; prevention group;
      and treatment group. SSAO gene expression was analyzed by real-time quantitative
      polymerase chain reaction and its activity was determined. The activity of
      superoxide dismutase and content of malondialdehyde in the aorta and liver were
      also determined. In T0901317-treated mice, SSAO gene expression was significantly
      decreased in the aorta, liver, small intestine, and brain. SSAO activities in
      serum and in these tissues were also inhibited. The amount of superoxide
      dismutase in the aorta and liver of the prevention group and treatment group was
      significantly higher compared with the vehicle group (P<0.05). Malondialdehyde in
      the tissues of these two groups was significantly lower compared with the vehicle
      group (P<0.05). Our results showed that T0901317 inhibits SSAO gene expression
      and its activity in atherogenic apoE(-/-) mice. The atheroprotective effect of
      LXR agonist T0901317 is related to the inhibition of SSAO gene expression and its
      activity.

PMID- 18330482
TI  - Procidentia: a reversible cause of hydronephrosis in an 80-year-old woman.
AB  - We describe an unusual presentation of hydronephrosis in an 80-year-old woman who
      was managed conservatively after transfer to a specialist unit. This case
      highlights the role of accurate history taking and a focused physical examination
      in elderly female patients presenting with renal failure and hydronephrosis.

PMID- 18330483
TI  - Prospective randomized comparison of oxybutynin, functional electrostimulation,
      and pelvic floor training for treatment of detrusor overactivity in women.
AB  - The purpose of this study is to compare the effectiveness of oxybutynin,
      functional electrostimulation (FES), and pelvic floor training (PFT) for
      treatment of women with detrusor overactivity. Sixty-four subjects were
      randomized to oxybutynin (n=22), FES (n=21), or PFT (n=21). Women were evaluated
      before and after completion of 12 weeks of treatment by subjective response,
      voiding diary, and urodynamic test. There was subjective symptomatic improvement
      in 77% of the women treated with oxybutynin, 52% with FES, and 76% with PFT.
      Urgency resolved in 64% of women treated with oxybutynin, 52% with FES, and in
      57% with PFT. Urodynamic evaluation was normal in 36% treated with oxybutynin,
      57% with FES, and 52% with PFT. Maximum detrusor involuntary contraction pressure
      decreased in all groups (p<0.05). All treatments were equally effective.
      Subjective reduction of urge-incontinence episodes was associated with
      symptomatic improvement.

PMID- 18330484
TI  - Trigeminal nitric oxide synthase expression correlates with new bone formation
      during distraction osteogenesis.
AB  - Nitric oxide synthase (NOS) has been reported to be involved with both bone
      healing and bone metabolism. The aim of this study was to test the null
      hypothesis that there is no correlation between new bone formation during
      mandibular distraction osteogenesis and NOS expression in the trigeminal ganglion
      of rats. Newly formed tissue during distraction osteogenesis and trigeminal NOS
      expression measured by the NADPH-diaphorase (NADPH-d) reaction were evaluated in
      72 male Wistar rats by histomorphometric and histochemical methods. In animals
      submitted to 0.5 mm/day distraction osteogenesis, the percentage of bone tissue
      was higher in the basal area of the mandibles compared with the center and
      significantly increased through the experimental periods (P < 0.05). At the sixth
      postoperative week, the difference in bone formation between the continuous and
      acute distraction osteogenesis groups was the highest. Significant correlation
      between new bone formation by distraction osteogenesis and NADPH-d-reactive
      neurons was found, varying according to neuronal cell size (r = -0.6, P = 0.005,
      small cells strongly stained; r = 0.5, P = 0.018, large cells moderately
      stained). The results suggest that NOS may play a role in the bone healing
      process via neurogenic pathways, and the phenomenon seems to be neuronal cell
      morphotype-dependent. Further studies are now warranted to investigate the
      mechanistic link between the expression of trigeminal NOS and mandibular new bone
      formation by distraction osteogenesis.

PMID- 18330485
TI  - Extensive rearrangements in the chloroplast genome of Trachelium caeruleum are
      associated with repeats and tRNA genes.
AB  - Chloroplast genome organization, gene order, and content are highly conserved
      among land plants. We sequenced the chloroplast genome of Trachelium caeruleum L.
      (Campanulaceae), a member of an angiosperm family known for highly rearranged
      genomes. The total genome size is 162,321 bp, with an inverted repeat (IR) of
      27,273 bp, large single-copy (LSC) region of 100,114 bp, and small single-copy
      (SSC) region of 7,661 bp. The genome encodes 112 different genes, with 17
      duplicated in the IR, a tRNA gene (trnI-cau) duplicated once in the LSC region,
      and a protein-coding gene (psbJ) with two duplicate copies, for a total of 132
      putatively intact genes. ndhK may be a pseudogene with internal stop codons, and
      clpP, ycf1, and ycf2 are so highly diverged that they also may be pseudogenes.
      ycf15, rpl23, infA, and accD are truncated and likely nonfunctional. The most
      conspicuous feature of the Trachelium genome is the presence of 18 internally
      unrearranged blocks of genes inverted or relocated within the genome relative to
      the ancestral gene order of angiosperm chloroplast genomes. Recombination between
      repeats or tRNA genes has been suggested as a mechanism of chloroplast genome
      rearrangements. The Trachelium chloroplast genome shares with Pelargonium and
      Jasminum both a higher number of repeats and larger repeated sequences in
      comparison to eight other angiosperm chloroplast genomes, and these are
      concentrated near rearrangement endpoints. Genes for tRNAs occur at many but not
      all inversion endpoints, so some combination of repeats and tRNA genes may have
      mediated these rearrangements.

PMID- 18330486
TI  - High incidence of interchromosomal transpositions in the evolutionary history of
      a subset of or genes in Drosophila.
AB  - In insects, the odorant receptor (Or) multigene family is an intermediate-sized
      family with genes present in all chromosomes, indicating that duplication
      followed by interchromosomal transposition played an important role in the early
      stages of the family evolution. Here, we have explored the occurrence of
      interchromosomal transpositions in more recent stages through the comparative
      analysis of a subset of Or genes in Drosophila, where the gene content of
      chromosomal arms is highly conserved. The studied subset consisted of 11 Or genes
      located on the left arm of chromosome 3 (Muller's D element) in D. melanogaster.
      Our study focused on the number and chromosomal arm location of these members of
      the family across the 12 Drosophila species with complete genome sequences. In
      contrast to previous results from in situ hybridization comparative mapping that
      were mainly based on single-copy genes, our study, based on members of a
      multigene family of moderate size, revealed repeated interchromosomal
      transposition events and a complex history of some of the studied genes.

PMID- 18330487
TI  - Topography of carotid bifurcation: considerations for neck examination.
AB  - Clinical examination and surgical procedures require the knowledge of anatomical
      structures of such a complex area as neck, especially the developmental anomalies
      in vascular drainage may occur. The aim of this study was to describe the common
      carotid artery bifurcation to its surrounding structures to locate it properly by
      using external and internal landmarks. Measurements were performed on 43 Thai
      cadavers by the direct inspection method. Carotid bifurcation level was compared
      to the level of cervical vertebra, isthmus of thyroid cartilage, angle of
      mandible and origins of superior thyroid artery, and lingual artery. Most of
      carotid bifurcations were found at the level of C3, between C3 and C4, and C4
      vertebra, as well as the tendency to lower position in men was noted.
      Measurements to the angle of mandible on the left sides were significantly
      different in studied groups (P = 0.02), also with lower position of bifurcation
      in men. The mean level of carotid bifurcation was approximately 6 mm above ITC,
      which literally is at the level of the superior border of thyroid cartilage.
      Moreover, in four cases, common carotid artery did not bifurcate bilaterally, and
      in four cases, no bifurcations were found at the right side of neck. Further,
      many superior thyroid arteries originated from common carotid artery. To sum up,
      during the clinical procedures, the level of thyroid cartilage is mostly advised
      to follow to locate the carotid sinus. Further, the described variations in
      topography of carotid bifurcation and arteries origins may have important
      clinical implications.

PMID- 18330488
TI  - Effects of the adducted or abducted position of the arm on the course of the
      musculocutaneous nerve during anterior approaches to the shoulder.
AB  - Nerve injury is a common complication during anterior shoulder surgery. The
      purpose of the study was to evaluate the musculocutaneous nerve (MN) anatomically
      and to clarify the relationship of the MN to the glenoid labrum and coracoid
      process in different arm positions. The study was carried out on 40 shoulders of
      20 adult cadavers fixed in 10% formaldehyde. The minimum distance of the MN at
      the entrance point of the nerve into the coracobrachialis to the anteromedial
      aspect of the coracoid tip and the distance between the MN and the top, middle,
      and inferior points of the glenoid labrum were measured. All measurements were
      performed with a digital caliper while the arm was in a neutral position, 45
      degrees and 90 degrees of abduction, 90 degrees of abduction-internal rotation
      and 90 degrees of abduction-external rotation to evaluate whether arm position
      effects the results statistically or not. The results demonstrated that the
      position of the arm significantly changes the distance between the coracoid
      process (CP) and the MN or its cord. The change in distance between the glenoid
      labrum and the MN or its cord was also statistically significant. The distance
      between the CP and MN was greatest when the arm was abducted to 45 degrees (mean
      3.4 cm) and least when the arm was positioned to 90 degrees of abduction-internal
      rotation (mean 2.0 cm). While the distance between the MN and the coracoid
      process was least at 90 degrees of abduction and internal rotation, the distance
      between the MN and glenoid labrum was lest with 90 degrees of abduction and
      external rotation. The distance between the glenoid labrum and MN was greatest
      with 45 degrees of abduction. The results of this study might be of use in
      avoiding the MN especially during Bristlow operations and certain rotator cuff
      procedures. Transferring the coracoid process during Bristow operations or
      placing arthroscopic portals when the arm is abducted to 45 degrees appears to be
      the safest position in terms of MN injury. Based on our results, when the arm
      needs to be abducted to 90 degrees during operation, externally rotating it may
      decrease the tension on the brachial plexus thus increasing the distance between
      the MN and the portals or retractors.

PMID- 18330489
TI  - Clinical anatomy of the retrocalcaneal bursa.
AB  - The goal of the study was to perform a detailed anatomical description of the
      retrocalcaneal bursa (RB). Its morphological arrangement was studied on 10 fresh
      and 30 embalmed lower extremities by microdissection and light microscopy. The RB
      was present constantly and in all the cases contained 1-2 cm long synovial fold,
      beginning on the upper wall of RB and distally interposed between the anterior
      surface of the Achilles tendon and the posterior surface of the calcaneal
      tuberosity. The volume of RB was 1-1.5 ml. The histological analysis confirmed
      that the inner surface of the superior and posterior wall of RB have been covered
      by unilayered synovial membrane, projecting into synovial villi of different
      shapes and sizes. In the ceiling of RB, delicate fascicle of skeletal muscle
      fibers was discovered, radiating distally into the regularly present synovial
      fold. The whole bottom of RB has been covered by 200-500 microm layer of fibrous
      cartilage into which the calcaneal tendon attached. The cartilagineous layer
      continued anteroproximally to cover the whole bursal surface of the calcaneal
      tuberosity, where the thickness of the cortical bone was reduced on mere 50
      microm. The obtained results can be used in the improvement of the differential
      diagnostics and therapy of diagnostics and therapy of the retrocalcaneal bursitis
      as well as of other kinds of achillar enthesopathies and heel pain.

PMID- 18330490
TI  - Anatomical bases of the surgical dissection of the interatrial septum: a
      morphological and histological study.
AB  - BACKGROUND: The interatrial septum (IAS) can be dissected to resect pulmonary
      tumors invading the left atrium. The aim of this study was to describe the
      dissected structures, and to expose the benefits, the limits, and the embryologic
      reasons of such dissection. METHODS: We dissected the IAS of 11 fresh, non
      embalmed human hearts. The dissected structures were described and the length and
      depth of the dissection were measured. A histological study was performed in four
      other fresh hearts to identify and differentiate between dissectible and non
      dissectible structures. RESULTS: The dissection was performed through a fatty
      tissue located between two muscular walls. The depth limit of the IAS dissection
      was identified as the limbus of the fossa ovalis and the muscular roof of the
      atria. The section of the latter doubles the depth of the dissection at the level
      of the upper pulmonary veins. Mean length of the dissected IAS was 77 mm (55-90).
      Mean depths of the IAS were 41 mm (35-50) at the level of the left upper
      pulmonary vein, 27 mm (12-35) between the upper and lower pulmonary veins, and 14
      mm (8-20) at the level of the left inferior pulmonary vein CONCLUSION: The
      surgical dissection of the IAS is performed through the septum secundum that
      appears as an infold of the atrial wall. The length of the resectable left atrial
      cuff reaches a mean of 40 mm at the level of the upper pulmonary vein.

PMID- 18330491
TI  - Venous drainage of the soleus muscle.
AB  - Soleus veins have been implicated as the site for deep venous thrombosis
      initiation. Detailed anatomic knowledge is required for the early diagnosis using
      non-invasive ultrasound techniques. In the present work, we describe the anatomy
      of the veins that emerge from the ventral face of the soleus muscle. Twenty-eight
      soleus muscles were dissected and 543 veins were found. The number of veins per
      leg ranged from 7 to 38. The distribution of these veins per quadrant ranged from
      0 to 12. The greatest number of veins occurred at the superior lateral quadrant.
      Most soleus veins mainly drained into the posterior tibial and fibular veins. The
      mean length of the soleus veins ranged from 0.907 to 2.804 cm. We conclude that
      there is a wide variability in the distribution of soleus veins through the
      soleus muscle and their quadrants. The majority of the soleus veins drain into
      the tibial and fibular veins.

PMID- 18330492
TI  - Abnormalities of the gallbladder, clinical effects.
AB  - The aim of this review of the literature was to present and discuss the
      anatomical and embryological basis of congenital abnormalities of the
      gallbladder, based on a case of volvulus. In the rare cases of ectopic
      gallbladder, diagnosis of a biliary disease could be difficult. In such cases
      surgery can also be dangerous, especially when it is associated with
      abnormalities of the intra-hepatic biliary and vascular tree. This study, based
      on the embryology of the extra hepatic bile duct, focused on the most frequent
      gallbladder abnormalities to keep them in mind.

PMID- 18330494
TI  - Antithrombotic triple therapy in a patient with multiple thrombi, subacute
      myocardial infarction and coronary stent implantation.

PMID- 18330493
TI  - Allopurinol improves endothelial function and reduces oxidant-inflammatory enzyme
      of myeloperoxidase in metabolic syndrome.
AB  - OBJECTIVE: In this study, we tested in patients with metabolic syndrome whether
      allopurinol through decreasing oxidative stress improves endothelial function,
      and ameliorates inflammatory state represented by markers of myeloperoxidase, C
      reactive protein (CRP) and fibrinogen. METHODS: In a randomized, double-blind
      fashion; subjects with metabolic syndrome were treated with allopurinol (n = 28)
      or placebo (n = 22) for one month. Before and after treatment, blood samples were
      collected and the flow-mediated dilation (FMD) and isosorbide dinitrate (ISDN)
      mediated dilation of the brachial artery were performed. RESULTS: Baseline
      clinical characteristics of the allopurinol and placebo groups demonstrated no
      differences in terms of clinical characteristics, endothelial function and
      inflammatory markers. After the treatment with allopurinol, FMD was increased
      from 8.0 +/- 0.5 % to 11.8 +/- 0.6% (P < 0.01), but there were no change in the
      placebo group. In both groups, ISDN-mediated dilation is unaffected by the
      treatment. As a marker of oxidative stress, allopurinol significantly reduced
      malondialdehyde. Moreover, myeloperoxidase levels were reduced by the treatment
      with allopurinol (56.1 +/- 3.4 ng/ml vs. 44.4 +/- 2.4 ng/ml, P < 0.05) but there
      were no change in the placebo group. Surprisingly, neither CRP nor fibrinogen
      levels were affected by the treatment in both groups. CONCLUSION: Xanthine
      oxidoreductase inhibition by allopurinol in patients with metabolic syndrome
      reduces oxidative stress, improves endothelial function, ameliorates
      myeloperoxidase levels and does not have any effect on CRP and fibrinogen levels.

PMID- 18330495
TI  - Yams (Dioscorea spp.) from the South Pacific Islands contain many novel
      badnaviruses: implications for international movement of yam germplasm.
AB  - Yam (Dioscorea spp.) samples (n = 690) from seven South Pacific Islands were
      screened for badnavirus infection by ELISA using two antisera to African
      badnaviruses. Positive readings were obtained for 26.4-34.6% of samples
      representing both known (D. bulbifera, D. nummularia and D. pentaphylla) and
      unreported host species (D. alata, D. esculenta, D. rotundata and D. trifida) in
      this region. Total DNAs were extracted from 25 ELISA-positive plants and 4 ELISA
      negative controls and subjected to PCR amplification with badnavirus-specific
      primers targeting the reverse transcriptase (RT)-RNaseH genes. All 29 samples
      yielded the expected size PCR-product for badnaviruses, which were cloned and
      sequenced. Phylogenetic analyses of the resulting 45 partial (500-527 bp) RT
      RNaseH sequences revealed 11 new sequence groups with <79% nucleotide identity to
      each other or any EMBL sequence. Three sequences (two groups) were highly
      divergent to the other nine new South Pacific yam badnavirus groups (47.9-57.2%
      identity) and probably represent either new Caulimoviridae genera or endogenous
      pararetrovirus sequences. Some sequence groups appeared specific to particular
      Dioscorea host species. Four 99.9% identical RT-RNaseH sequences possessing nine
      amino acid deletions from D. esculenta from three islands represent a putative
      integrated sequence group. The distribution of sequence groups across the islands
      indicates that badnaviruses have spread extensively between islands and
      continents through infected germplasm.

PMID- 18330496
TI  - Viral morphogenesis and morphological changes in human neuronal cells following
      Tioman and Menangle virus infection.
AB  - Tioman virus (TioPV) and Menangle virus (MenPV) are two antigenically and
      genetically related paramyxoviruses (genus: Rubulavirus, family: Paramyxoviridae)
      isolated from Peninsular Malaysia (2001) and Australia (1997), respectively. Both
      viruses are potential zoonotic agents. In the present study, the infectivity,
      growth kinetics, morphology and morphogenesis of these two paramyxoviruses in a
      human neuronal cell (SK-N-SH) line were investigated. Sub-confluent SK-N-SH cells
      were infected with TioPV and MenPV at similar multiplicity of infection. These
      cells were examined by conventional and immunoelectron microscopy, and virus
      titres in the supernatants were assayed. Syncytia were observed for both
      infections in SK-N-SH cells and were more pronounced during the early stages of
      TioPV infection. The TioPV titre increased consistently (10(1)) every 12 h after
      infection. In MenPV-infected cells, cellular material was frequently observed
      within budding virions, and microfilaments and microtubules were abundant. Viral
      budding was common, and extracellular MenPVs tended to be more pleomorphic
      compared to TioPVs, which appeared to be more spherical in appearance. The MenPV
      cytoplasmic viral inclusion appeared to be comparatively smaller, loose and
      interspersed with randomly scattered circle-like particles, whereas huge tubule
      like cytoplasmic inclusions were observed in TioPV-infected cells. Both viruses
      also displayed different cellular pathology in the SK-N-SH cells. The
      intracellular ultrastructural characteristics of these two viruses in infected
      neuronal cells may allow them to be differentiated by electron microscopy.

PMID- 18330497
TI  - Proline metabolism in the conceptus: implications for fetal growth and
      development.
AB  - Although there are published studies of proline biochemistry and nutrition in
      cultured cells and postnatal animals, little is known about proline metabolism
      and function in the conceptus (embryo/fetus, associated placental membranes, and
      fetal fluids). Because of the invasive nature of biochemical research on
      placental and fetal growth, animal models are often used to test hypotheses of
      biological importance. Recent evidence from studies with pigs and sheep shows
      that proline is a major substrate for polyamine synthesis via proline oxidase,
      ornithine aminotransferase, and ornithine decarboxylase in placentae. Both
      porcine and ovine placentae have a high capacity for proline catabolism and
      polyamine production. In addition, allantoic and amniotic fluids contain enzymes
      to convert proline into ornithine, which is delivered through the circulation to
      placental tissues. There is exquisite metabolic coordination among integrated
      pathways that support highest rates of polyamine synthesis and concentrations in
      placentae during early gestation when placental growth is most rapid.
      Interestingly, reduced placental and fetal growth are associated with reductions
      in placental proline transport, proline oxidase activity, and concentrations of
      polyamines in gestating dams with either naturally occurring or malnutrition
      induced growth retardation. Conversely, increasing proline availability in
      maternal plasma through nutritional or pharmacological modulation in pigs and
      sheep enhances concentrations of proline and polyamines in placentae and fetal
      fluids, as well as fetal growth. These novel findings suggest an important role
      for proline in conceptus metabolism, growth and development, as well as a
      potential treatment for intrauterine growth restriction, which is a significant
      problem in both human medicine and animal agriculture.

PMID- 18330498
TI  - Regulatory mechanisms of SNAT2, an amino acid transporter, in L6 rat skeletal
      muscle cells by insulin, osmotic shock and amino acid deprivation.
AB  - Several studies have demonstrated that the activity of system A is upregulated by
      insulin, osmotic shock and amino acid deprivation. However, the mechanisms are
      not clear. We carried out studies using L6 rat skeletal muscle cells to clarify
      the mechanisms of upregulation of system A activity by insulin, osmotic shock and
      amino acid deprivation. The upregulation was found to be due to an increase in
      Vmax, not Km. Chloroquine and wortmannin inhibited the upregulation induced by
      insulin stimulation and amino acid deprivation but not that induced by osmotic
      shock. On the other hand, cycloheximide and actinomycin D inhibited the
      upregulation by each stimulation. Moreover, PD98059 and SP600125 inhibited only
      amino acid deprivation-induced upregulation and SB202190 inhibited only insulin
      induced upregulation. Our findings indicate that the mechanisms of upregulation
      of system A activity by insulin, osmotic shock and amino acid deprivation are
      different in L6 cells. Western blot and RT-PCR analysis showed an increase in
      system A at the protein and mRNA levels with each stimulation.

PMID- 18330499
TI  - Extremely thermostable esterases from the thermoacidophilic euryarchaeon
      Picrophilus torridus.
AB  - Two genes encoding esterases EstA and EstB of Picrophilus torridus were
      identified by the means of genome analysis and were subsequently cloned in
      Escherichia coli. PTO 0988, which is encoding EstA, consists of 579 bp, whereas
      PTO 1141, encoding EstB, is composed of 696 bp, corresponding to 192 aa and 231
      aa, respectively. Sequence comparison revealed that both biocatalysts have low
      sequence identities (14 and 16%) compared to previously characterized enzymes.
      Detailed analysis suggests that EstA and EstB are the first esterases from
      thermoacidophiles not classified as members of the HSL family. Furthermore, the
      subunits with an apparent molecular mass of 22 and 27 kDa of the homotrimeric
      EstA and EstB, respectively, represent the smallest esterase subunits from
      thermophilic microorganisms reported to date. The recombinant esterases were
      purified by Ni2+ affinity chromatography, and the activity of the purified
      esterases was measured over a wide pH (pH 4.5-8.5) and temperature range (10-90
      degrees C). Highest activity of the esterases was measured at 70 degrees C (EstA)
      and 55 degrees C (EstB) with short pNP-esters as preferred substrates. In
      addition, esters of the non-steroidal anti-inflammatory drugs naproxen,
      ketoprofen, and ibuprofen are hydrolyzed by both EstA and EstB. Extreme
      thermostability was measured for both enzymes at temperatures as high as 90
      degrees C. The determined half-life (t1/2) at 90 degrees C was 21 and 10 h for
      EstA and EstB, respectively. Remarkable preservation of esterase activity in the
      presence of detergents, urea, and commonly used organic solvents complete the
      exceptional phenotype of EstA and EstB.

PMID- 18330500
TI  - Local crystalline order in a 2D colloidal glass former.
AB  - A mixture of two types of super-paramagnetic colloidal particles with long-range
      dipolar interaction is confined by gravity to a flat interface of a hanging water
      droplet. The particles are observed by video microscopy and the dipolar
      interaction strength is controlled by an external magnetic field. The local
      structure as obtained by pair correlation functions and bond order statistics is
      investigated as a function of system temperature and relative concentration.
      Although the system has no long-range order and exhibits glassy dynamics,
      different types of stable crystallites coexist. The local order of the globally
      disordered structure is explained by a small set of specific crystal structures.
      The statistics of crystal unit cells show a continuous increase of local order
      with decreasing system temperature as well as a dependence on sample history and
      local composition.

PMID- 18330501
TI  - Equilibrium statistical distributions for subchains in an entangled polymer melt.
AB  - In de Gennes-Doi-Edwards theory for entangled polymeric melts, a length scale
      r(0) is introduced, giving the equilibrium mesh size of the physical network of
      chains. Each polymer molecule is then represented as a random walk, with a step
      size r(0) (a "subchain", made up of n(0) Kuhn segments) dictated by the existence
      of entanglements. Progressing from this simple picture, an issue that has been
      constantly overlooked so far, despite its potential relevance, is that of finite
      size effects at the de Gennes-Doi-Edwards characteristic length scale. Actually,
      since a subchain in a melt is a "small", nonmacroscopic system, fluctuations of
      both its length and its number of Kuhn segments are certainly nonnegligible. An
      ad hoc theoretical treatment from nonstandard (nano) statistical mechanics and
      thermodynamics seems then required, to find the anticipated equilibrium
      statistical distributions of the subchain population. In this contribution, we
      carefully discuss this topic. Some predictions from the nonstandard fluctuation
      inclusive approach on the statistics of subchains are here obtained, and compared
      with existing simulations, even down to the atomistic level.

PMID- 18330502
TI  - Organization of membrane-associated proteins in lipid bilayers.
AB  - Lateral organization of proteins in biomembranes is vitally important to membrane
      functions such as signal transduction, endocytosis, and membrane trafficking. One
      of the major goals in current biomembrane science is to reveal the microscopic
      mechanism of membrane-associated protein organization in biomembranes. Here, we
      investigate the structural organization of membrane-associated proteins in lipid
      bilayers by combining self-consistent field theory with density functional
      theory. The present study can simultaneously take into account the entropy effect
      of lipids, depletion effect of membrane-associated proteins due to the presence
      of lipid headgroups as well as the effect of interfacial interaction. By varying
      the volume fraction of lipids, we examine various effects on protein
      organization, and reveal that a close-packed crystal structure appears at low
      lipid volume fractions due to interfacial energy and weak depletion effect,
      whereas a chain structure with branches occurs at high lipid volume fractions
      mainly due to strong depletion. The present results may provide some theoretical
      insight into further experiments on organization of membrane proteins.

PMID- 18330503
TI  - Spontaneous processes and stable structures in some three-phase cellular fluids.
AB  - Cellular fluids are systems consisting of a collection of fluid cells surrounded
      by thin liquid films. In this study, systems composed of two different kinds of
      cells (i.e., filled with fluids A and B) immersed in a third fluid phase (a
      liquid C) have been examined. The object of the study is a collection of
      polyhedra of fluid B separated by a thin film of liquid C (a host B/C network),
      modified by the insertion of small droplets/bubbles of fluid A. Interfacial
      tensions acting along the A-C and B-C interfaces are assumed to be the only
      driving forces determining the structure of the resulting mixed system. Different
      configurations of mixed A/B/C systems, formed by the insertion of A singlets or
      doublets into the nodes, edges, films and interior parts of cells of the B/C
      network have been analyzed in terms of the interfacial energy of the system. The
      possibility of spontaneous migration of cells A through the B/C network and the
      possible final cell arrangements have been examined.

PMID- 18330504
TI  - Increased activity of serotonin uptake in platelets in medication overuse
      headache following regular intake of analgesics and triptans.
AB  - We investigated the effect of chronic administration of different pain
      medications on the activity of the serotonin transporter (SERT) in patients with
      medication overuse headache (MOH). We measured the kinetic of platelet 5-HT
      uptake (maximal velocity, Vmax and the Michaelis-Menten constant, Km in patients
      with overuse of triptans (tMOH, n = 15) or analgesics (aMOH, n = 14) before and
      after drug withdrawal, as well as in headache-free healthy subjects (n = 15) and
      patients with episodic migraine (EM, n = 16). Vmax was increased similarly in
      both, tMOH and aMOH compared to healthy subjects and patients with EM and
      normalized after withdrawal in parallel to the improvement of headache frequency.
      Average Km was similar in all groups at baseline and not affected by the
      withdrawal. The data demonstrate a transient increase of SERT activity in
      patients with analgesic and triptan induced MOH but do not allow to differentiate
      whether the increase of serotonin uptake is caused by regular intake of
      analgesics or triptans or is a consequence of frequent headache attacks.

PMID- 18330505
TI  - Influence of steroids on procalcitonin and C-reactive protein in patients with
      COPD and community-acquired pneumonia.
AB  - BACKGROUND: The induction of C-reactive Protein (CRP) may be attenuated by
      corticosteroids, whereas Procalcitonin (PCT) appears to be unaltered. We
      investigated, whether in community-acquired pneumonia (CAP) a combined antibiotic
      corticosteroid therapy may actually lead to different slopes of decline of these
      inflammatory markers. PATIENTS AND METHODS: We studied the slopes of decline of
      PCT and CRP serum levels during 7 consecutive days as well as clinical parameters
      in a group of patients with CAP on or off corticosteroids. Patients with
      underlying COPD received systemic corticosteroids (n = 10), while non-COPD
      patients (n = 10) presenting with CAP alone formed the control group. All
      patients were treated with antibiotics. RESULTS: At baseline, relevant clinical
      and laboratory characteristics of the two groups were similar. Regarding the
      decreasing shapes of the curves from PCT and CRP, no significant differences were
      found (p-value = 0.48 for the groups for CRP, respectively 0.64 for PCT). All
      patients showed an uneventful recovery. CONCLUSION: In patients with COPD and
      CAP, the time courses over 7 days of PCT and CRP showed a nearly parallel decline
      compared to non-COPD patients with CAP. Contrary to the induction phase,
      corticosteroids do not modify the time-dependent decay of PCT and CRP when the
      underlying infectious disease (CAP) is adequately treated.

PMID- 18330506
TI  - Evidence of a TH1-shift of local vaginal inflammatory response during bacterial
      vaginosis.
AB  - OBJECTIVE: To determine the levels of pro-inflammatory and anti-inflammatory
      cytokines in the vagina of healthy women and in bacterial vaginosis (BV)
      patients. METHODS: Interleukin (IL)-1alpha, 1beta, 5 and 10 were analyzed by
      ELISA in vaginal wash fluids from 50 non-pregnant patients with BV and 112
      healthy women. RESULTS: Levels of IL-1beta were higher and those of IL-10 lower
      in BV-patients than in healthy women. There was a tendency towards higher levels
      of IL-1alpha in BV patients, but these data were not statistically significant.
      CONCLUSION: We found evidence for a shift towards a TH1-dominated vaginal
      cytokine profile in the pathogenesis of BV. Levels of a TH1-cytokine were
      elevated and those of a TH2-cytokine lowered in BV-patients as compared to
      healthy controls. This points to a vaginal TH1-response during BV and to the
      importance of cell-mediated immunity in local vaginal infections.

PMID- 18330507
TI  - Seroepidemiology and molecular characterization of hepatitis E virus in Jilin,
      China.
AB  - BACKGROUND: In order to develop region-specific diagnostic assays and prevent
      hepatitis E virus (HEV), it is essential to understand epidemiology and genotypic
      variation within different populations. However, the epidemiological data of HEV
      infections in Jilin is shortage. METHODS: The seroepidemiological study was
      conducted by enzyme-linked immunosorbent assay, and the conserved genomic
      sequences of open reading frame 2 (348 bp) was detected using reverse
      transcription-PCR. RESULTS: Overall, 1,289 serum samples were positive to HEV
      specific immunoglobulin G (IgG), and 180 serum samples were positive to HEV
      specific immunoglobulin M (IgM). The seroprevalence of HEV-specific IgG was
      26.3%, 27.9%, 25.3%, 32.7% in 2003, 2004, 2005, 2006, respectively. Acute HEV
      infection mainly occurred in male, people aged from 20 to 69 were more
      susceptible to infection, and cases with IgM anti-HEV reaction mainly occurred
      from July to November. HEV RNA was detectable in the serum samples or stool
      suspension of 15 patients with HEV-specific IgM, and all of these belonged to
      genotype IV. CONCLUSIONS: Our results indicate that HEV is widely spread in Jilin
      and confined to genotype IV.

PMID- 18330508
TI  - Erythropoiesis-stimulating agents: favorable safety profile when used as
      indicated.
AB  - BACKGROUND AND PURPOSE: Several studies with erythropoiesis-stimulating agents
      (ESAs) have raised a number of safety issues. Therefore, a discussion of
      available data in light of the current EORTC guidelines 2006 on the use of ESAs
      in anemic patients is warranted. METHODS: Literature is reviewed with respect to
      experimental and clinical data on the effect of ESA therapy on tumor growth both
      in the preclinical setting and on patient survival. RESULTS: Studies showing an
      adverse effect of ESA therapy on patient survival generally exhibit considerable
      methodological deficiencies. Moreover, they investigated treatment situations for
      which ESAs are not approved and/or did not involve recommended baseline
      ("intervention") or target hemoglobin levels. CONCLUSION: When used as indicated,
      ESAs are valuable and safe drugs for the treatment of anemia and do not
      negatively affect patient survival. In particular, the data situation confirms
      the importance and correctness of the EORTC guidelines 2006 and their recently
      updated version. It is therefore recommended that these guidelines continue to be
      strictly followed in the treatment of chemotherapy-induced anemia.

PMID- 18330509
TI  - [Long-term results following multidisciplinary treatment of localized Ewing's
      sarcoma in children and adolescents].
AB  - PURPOSE: To identify results and prognostic factors on long-term survival and
      local control following treatment of localized Ewing's sarcoma. PATIENTS AND
      METHODS: Between 1979 and 2004, a total of 60 children and young adults with
      Ewing's sarcoma were treated. Patients with distant metastases at presentation (n
      = 6) and recurrent cases (n = 2) were excluded from this analysis. Patients were
      exclusively treated within ongoing national and international protocols CESS-81,
      CESS-86, EICESS-92, EURO-EWING-99. All patients received local irradiation with a
      total dose of 45-60 Gy; in addition, 41 (79%) of the patients had local surgical
      procedures, 27 (52%) of them with clear margins. RESULTS: Overall survival rates
      at 5 and 10 years were 56% and 45%, respectively. Patients <or= 14 years at
      diagnosis had overall survival rates of 66% and 61% at 5 and 10 years compared to
      older patients with corresponding survival rates of 47% and 31%, respectively (p
      = 0.05). Patients with tumors of lower volume (<or= 100 ml) had significantly
      better survival rates at 5 and 10 years: 82% and 60% versus 42% und 39% (p =
      0.03). Seven of 52 (14%) patients experienced local failure; no significant
      impact was noted for any of the following factors: treatment protocol, radiation
      dose, surgery. CONCLUSION: Radiotherapy with and without surgery of Ewing's
      sarcoma is a highly effective local treatment option. It seems preferable to
      mutilating surgery.

PMID- 18330510
TI  - Helical tomotherapy as a new treatment technique for whole abdominal irradiation.
AB  - PURPOSE: To describe a new intensity-modulated radiotherapy (IMRT) technique
      using helical tomotherapy for whole abdominal irradiation (WAI) in patients with
      advanced ovarian cancer. MATERIAL AND METHODS: A patient with radically operated
      ovarian cancer FIGO stage IIIc was treated in a prospective clinical trial with
      WAI to a total dose of 30 Gy in 1.5-Gy fractions as an additional therapy after
      adjuvant platinum-based chemotherapy. The planning target volume (PTV) included
      the entire peritoneal cavity. PTV was adapted according to breathing motion as
      detected in a four-dimensional respiratory-triggered computed tomography (4D-CT).
      Inverse treatment planning was done with the Hi-Art tomotherapy planning station.
      Organs at risk (OARs) were kidneys, liver, bone marrow, spinal cord, thoracic and
      lumbosacral vertebral bodies, and pelvic bones. Daily control of positioning
      accuracy was performed with megavoltage computed tomography (MV-CT). RESULTS:
      Helical tomotherapy enabled a very homogeneous dose distribution with excellent
      sparing of OARs and coverage of the PTV (V90 of 93.1%, V95 of 86.9%, V105 of
      1.9%, and V110 of 0.01%). Mean liver dose was 21.57 Gy and mean kidney doses were
      9.75 Gy and 9.14 Gy, respectively. Treatment could be performed in 18.1 min daily
      and no severe side effects occurred. CONCLUSION: Helical tomotherapy is feasible
      and fast for WAI. Tomotherapy enabled excellent coverage of the PTV and effective
      sparing of liver, kidneys and bone marrow.

PMID- 18330511
TI  - Surgery with complete resection improves survival in radiooncologically treated
      patients with cervical lymph node metastases from cancer of unknown primary.
AB  - PURPOSE: To assess long-term toxicity, outcome and prognostic factors after
      multimodal treatment of cervical lymph node metastases from cancer of unknown
      primary (CUP). PATIENTS AND METHODS: In a retrospective study, the treatment
      results of 84 patients with CUP (median age 63 years, N1 n = 0, N2 n = 44, N3 n =
      39, Nx n = 1), treated between 1971 and 2002 with radiotherapy (n = 84, median
      dose 60 Gy), platinum-based chemotherapy (n = 23) and surgery (n = 69,
      tonsillectomy [n = 40], neck dissection [n = 52], suprahyoid dissection [n = 18],
      lymph node excision [n = 14]), were analyzed. RESULTS: After a mean follow-up
      time of 25 months (ranging from 0.1 to 260 months), the 3- and 5-year overall
      (disease-free) survival rates were 30% (39%) and 27% (34%), respectively. 75% of
      individuals achieved remission, whereas 23% showed no change or progression after
      treatment. The 3-, 5- and 10-year local control rates were 58%, 58% and 46%,
      respectively. 40% of patients suffered grade 3/4 late toxicity: severe skin
      contracture/induration (n = 2) and severe xerostomia (n = 32). Tonsillectomy (p =
      0.003) and neck dissection (p = 0.037) performed before radiotherapy
      significantly improved outcome. Other prognostic factors were age (p = 0.0235),
      extracapsular spread (n = 63; p = 0.0045), incomplete resection (n = 24; p =
      0.0026), nodal disease (p = 0.0034), and distant metastases (n = 17; p = 0.0002).
      After multivariate analysis only extracapsular spread (p = 0.004) and
      tonsillectomy (p = 0.01) showed impact on survival. CONCLUSION: Irradiation of
      cervical lymph node metastases from CUP is an effective treatment option with
      acceptable late toxicity. Complete tonsillectomy and neck dissection
      significantly improved survival in N2/N3 disease. Extracapsular spread was the
      best predictor for survival and local control. Prospective studies defining a
      standard treatment are needed.

PMID- 18330512
TI  - Functional changes of the gustatory organ caused by local radiation exposure
      during radiotherapy of the head-and-neck region.
AB  - PURPOSE: The aim of this prospective study was to investigate how often and at
      which dose levels gustatory disturbances appear during radiotherapy of the tongue
      and to which extent permanent gustatory deficiencies occur. PATIENTS AND METHODS:
      The study included 44 patients treated by definitive irradiation for malignant
      head-and-neck tumors. In 22 patients the posterior two thirds of the tongue
      (group 1), and in the other 22 patients the entire tongue (group 2) were exposed
      to radiation. The control group comprised 30 patients with non-small cell lung
      cancer receiving definitive radiation therapy (group 3). The dose distribution in
      the tongue area was calculated using CT-based three-dimensional planning. Before,
      during and after irradiation the gustatory function was determined by means of
      gustometry and correlated with the corresponding results of enoral inspection and
      the patients' subjective statements on gustatory function. RESULTS: The gustatory
      ability of the control group was not affected, whereas patients in the locally
      irradiated groups in parallel with enoral mucositis suffered from loss of
      gustatory function after a total dose of 20 Gy with a maximum between 40 and 60
      Gy. Supportive measures had little influence on acute side effects. The gustatory
      disturbances regressed within 8 weeks after radiotherapy in patients with partial
      tongue irradiation and almost completely after 6 months in patients with entire
      tongue irradiation. CONCLUSION: The severity of gustatory disturbances and the
      longer recovery time in patients with entire-tongue irradiation suggest an
      influence of the volume exposed. Therefore, reduction of the highly exposed
      tongue volume by intensity-modulated radiotherapy opens up possibilities for a
      reduction of this undesirable side effect.

PMID- 18330513
TI  - Radiochemotherapy in combination with regional hyperthermia in preirradiated
      patients with recurrent rectal cancer.
AB  - BACKGROUND AND PURPOSE: Encouraging results of phase II studies combining
      chemotherapy with radiotherapy have been published. In this study, the results of
      a multimodal salvage therapy including radiochemotherapy (RCT) and regional
      hyperthermia (RHT) in preirradiated patients with recurrent rectal cancer are
      reported. PATIENTS AND METHODS: All patients enrolled had received previous
      pelvic irradiation (median dose 50.4 Gy). The median time interval between prior
      radiotherapy and the onset of local recurrence was 34 months. The combined
      treatment consisted of reirradiation with a median dose of 39.6 Gy (30.0-45.0
      Gy), delivered in fractions of 1.8 Gy/day. 5-fluorouracil was given as continuous
      infusion 350 mg/m(2)/day five times weekly, and RHT (BSD-2000 system) was applied
      twice a week within 1 h after radiotherapy. The primary endpoint was local
      progression-free survival (LPFS); secondary endpoints were overall survival,
      symptom control, and toxicity. RESULTS: 24 patients (median age 59 years) with a
      previously irradiated locally recurrent adenocarcinoma of the rectum were
      enrolled. The median LPFS was 15 months (95% confidence interval 12-18 months]
      with a median follow-up of 27 months (16-37 months). The overall 1-year and 3
      year survival rates were 87% and 30%, respectively. Pain was the main symptom in
      17 patients. Release of pain was achieved in 12/17 patients (70%). No grade 3 or
      4 hematologic or skin toxicity occurred. Grade 3 gastrointestinal acute toxicity
      was observed in 12.5% of the patients. Paratumoral thermometry revealed a
      homogeneous distribution of temperatures. CONCLUSION: RCT combined with RHT is an
      efficient salvage therapy showing high efficacy with acceptable toxicity and can
      be recommended as treatment option for this unfavorable group of preirradiated
      patients with local recurrence of rectal cancer.

PMID- 18330514
TI  - Prognostic impact of HIF-1alpha expression in patients with definitive
      radiotherapy for cervical cancer.
AB  - PURPOSE: To investigate the relationship between the hypoxia-inducible factor
      (HIF-)1alpha expression in tumor tissue, tumor oxygenation and hemoglobin levels
      in patients with advanced cervical cancers prior to radiotherapy and the effect
      on clinical outcome. PATIENTS AND METHODS: The investigation included 44 patients
      who underwent definitive radiotherapy for advanced cervical cancers between May
      1995 and March 1999. Tumor biopsies were taken prior to treatment, and HIF-1alpha
      expression was determined by immunohistochemistry. In the same tumor area, tumor
      tissue oxygenation (pO2) was measured using the Eppendorf device. RESULTS: The 5
      year cancer-specific survival of all patients was 60%. Twelve of 44 tumor
      specimens were HIF-1alpha-negative with a significantly better 5-year survival
      (92 +/- 8%) versus 32 patients who were HIF-1alpha-positive (45 +/- 10%; p <
      0.02). There was no correlation between HIF-1alpha expression and tumor
      oxygenation (p = 0.57 both for pO2 median and hypoxic fraction < 5 mmHg vs. HIF
      1alpha expression). However, patients with hemoglobin levels < 11 g/dl showed
      elevated HIF-1alpha expression compared to patients with hemoglobin levels > 12.5
      g/dl (p = 0.04). Furthermore, HIF-1alpha correlated with vascular endothelial
      growth factor expression (p = 0.002). In a multivariate Cox regression model, HIF
      1alpha expression (relative risk [RR] = 7.5; p = 0.05) revealed an increased risk
      of tumor-related death. CONCLUSION: The study indicates, that endogenous tumor
      markers such as HIF-1alpha may serve as prognostic markers of clinical outcome
      concerning cervical cancer after primary radiotherapy.

PMID- 18330515
TI  - XRCC1 and XRCC3 variants and risk of glioma and meningioma.
AB  - Several single nucleotide polymorphisms (SNPs) affecting DNA repair capacity and
      modifying cancer susceptibility have been described. We evaluated the association
      of SNPs Arg194Trp, Arg280His, and Arg399Gln in the X-ray cross-complementing
      group 1 (XRCC1) and Thr241Met in the X-ray cross-complementing group 3 (XRCC3)
      DNA repair genes with the risk of brain tumors. The Caucasian study population
      consisted of 701 glioma (including 320 glioblastoma) cases, 524 meningioma cases,
      and 1,560 controls in a prospective population-based case-control study conducted
      in Denmark, Finland, Sweden, and the UK. The studied SNPs were not significantly
      associated with the risk of brain tumors. The highest odds ratios (ORs) for the
      associations were observed between the homozygous variant genotype XRCC1
      Gln399Gln and the risk of glioma (OR = 1.32; 95% confidence interval, CI, 0.97
      1.81), glioblastoma (OR = 1.48; 95% CI, 0.98-2.24), and meningioma (OR = 1.34;
      95% CI, 0.96-1.86). However, in pair-wise comparisons a few SNP combinations were
      associated with the risk of brain tumors: Among others, carriers of both
      homozygous variant genotypes, i.e., XRCC1 Gln399Gln and XRCC3 Met241Met, were
      associated with a three-fold increased risk of glioma (OR = 3.18; 95% CI, 1.26
      8.04) and meningioma (OR = 2.99; 95% CI, 1.16-7.72). In conclusion, no
      significant association with brain tumors was found for any of the polymorphisms,
      when examined one by one. Our results indicated possible associations between
      combinations of XRCC1 and XRCC3 SNPs and the risk of brain tumors.

PMID- 18330516
TI  - Association of angiographic perfusion score following percutaneous coronary
      intervention for ST-elevation myocardial infarction with left ventricular
      remodeling at 6 weeks in GRACIA-2.
AB  - Higher angiographic perfusion score (APS) following percutaneous coronary
      intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has
      been shown to be associated with improved clinical outcomes. The association
      between APS after STEMI and left ventricular remodeling as assessed by volumetric
      parameters derived from left ventriculography has not been assessed. METHODS: The
      APS (the arithmetic sum of the TIMI Flow Grade (TFG) and TIMI Myocardial
      Perfusion grade (TMPG) before and after percutaneous coronary intervention (PCI),
      range of 0-12) was assessed in 168 patients from the GRACIA-2 trial. Left
      ventriculograms performed in the 30 degrees right anterior oblique projection
      were obtained among 148 patients at initial angiography (prior to PCI) and at 6
      weeks. The association of APS with markers of left ventricular remodeling at 6
      weeks was examined using left ventricular ejection fraction, delta end systolic
      volume, delta stroke volume and wall motion index. RESULTS: Full perfusion (APS
      10-12), as compared to partial perfusion (APS 4-9) or failed perfusion (APS 0-3),
      was associated with a greater left ventricular ejection fraction (61.6% +/- 10.0
      vs. 56.9% +/- 12.5 vs. 49.8% +/- 16.9, P = 0.015), a decrease in left ventricular
      end systolic volume indicating favorable remodeling (mean -4.1 cc +/- 17.3 vs.
      +2.0 cc +/- 17.3 vs. +9.8 cc +/- 16.1, P = 0.015), a greater improvement in left
      ventricular stroke volume (mean +13.7 cc +/- 17.1 vs. +6.7 cc +/- 15.5 vs. +1.2
      cc +/- 13.4, P = 0.009) and a decreased wall motion index (number of chords in
      the hypokinetic region) (mean 15.1 +/- 16.4 vs. 21.4 +/- 20.5 vs. 32.9 +/- 22.1,
      P = 0.026) at 6 weeks. CONCLUSION: In conclusion, among patients treated with
      combined reperfusion and revascularization strategies for STEMI, higher APS is
      associated with more favorable markers of left ventricular remodeling and
      improved 6-week left ventricular function.

PMID- 18330517
TI  - Subunit fusion of two yeast D-amino acid oxidases enhances their thermostability
      and resistance to H2O2.
AB  - D-amino acid oxidases from Rhodosporidium toruloides and Trigonopsis variabilis
      (RtDAO and TvDAO) are both yeast homodimeric flavoenzymes. Two of their cDNA
      genes were connected by a hexanucleotide linker and heterologously expressed in
      E. coli to produce the corresponding double DAOs (dRtDAO and dTvDAO) with two
      subunits fused into a single polypeptide. The specific activities of double DAOs
      remained similar to those of native dimeric DAOs, although the catalytic
      efficiencies (k(cat)/K(M)) were decreased due to higher K(M) values. The T(m)
      value for dRtDAO was shifted 5 degrees C higher while that for dTvDAO was
      increased only by 2 degrees C, in comparison with the corresponding native
      counterparts. In the presence of 10 mM H(2)O(2), dRtDAO and dTvDAO exhibited half
      lives of about 60 and 40 min, respectively, which were 2- and 1.5-fold,
      respectively, longer than their native DAOs. These yeast DAOs can therefore be
      thermally and oxidatively stabilized by linking their subunits together.

PMID- 18330518
TI  - Flat-panel detector volumetric CT for visualization of subarachnoid hemorrhage
      and ventricles: preliminary results compared to conventional CT.
AB  - INTRODUCTION: The aim of this study was to compare flat-panel volumetric CT (VCT)
      to conventional CT (cCT) in the visualization of the extent of subarachnoid
      hemorrhage (SAH) and the width of the ventricles in patients with acute SAH.
      METHODS: Included in the study were 22 patients with an acutely ruptured cerebral
      aneurysm who received VCT during coil embolization. VCT image quality, the extent
      of SAH (using a modified Fisher score and total slice number with SAH visible)
      and the width of the ventricles (Evans index) were evaluated by two experienced
      neuroradiologists (RAD1 and RAD2) and compared to the findings on cCT. Ten
      patients undergoing VCT for reasons other than SAH served as negative controls.
      RESULTS: Interobserver agreement in rating image quality was excellent for cCT
      (Kendall W value 0.94) and good for VCT (0.74). SAH was identified by RAD1 and
      RAD2 on VCT images in all patients. The modified Fisher scores underestimated the
      extent of SAH on VCT images in comparison with cCT images. Pearson's correlation
      coefficient (r) regarding the number of image slices with SAH visible on cCT
      images compared with the number on VCT images was 0.85 for RAD1 and 0.84 for
      RAD2. The r value for the degree of interobserver agreement for the number of
      slices with SAH visible was 0.99 for cCT, and 0.95 for VCT images (n=19),
      respectively. The width of the ventricles measured in terms of the Evans Index
      showed excellent concordance between the modalities (r=0.81 vs. 0.82).
      CONCLUSION: Our preliminary results indicate that VCT is helpful in evaluating
      SAH in the angiography suite. Additionally, reliable evaluation of ventricle
      width is feasible. However, there are limitations with regard to the visibility
      of SAH on VCT images in comparison to cCT images.

PMID- 18330519
TI  - Endovascular treatment of tiny ruptured anterior communicating artery aneurysms.
AB  - INTRODUCTION: Because of its high complication rate, the endovascular treatment
      (EVT) of anterior communicating artery (ACoA) aneurysms less than 3 mm in maximum
      diameter remains controversial. We evaluated EVT of tiny ruptured ACoA aneurysms
      with Guglielmi detachable coils (GDCs). METHODS: We treated 19 ruptured ACoA
      aneurysms with a maximum diameter of <or=3 mm with GDCs. The pretreatment Hunt
      and Hess score was grade 1 in four patients, grade 2 in six, grade 3 in six, and
      grade 4 in three. The patients were clinically assessed before and after
      treatment and with multiple angiographic follow-up studies. RESULTS: All EVTs
      were successful; there were no aneurysm perforations or any other treatment
      related complications. In five patients older than 80 years the transfemoral
      approach was difficult, and the direct carotid approach was used. Complete and
      near-complete occlusion was achieved in 16 patients (84.2%) and 3 patients
      (15.8%), respectively. Of the 19 patients, 16 (84.2%) were followed
      angiographically for a median of 38.5 months (range 16-72 months). None
      demonstrated recanalization of the aneurysm requiring additional treatment. In 15
      patients (78.9%) the final outcome was good (modified Rankin scale, mRS, score 0
      2), and 3 patients (15.8%) died or suffered severe disability (mRS score 4-6).
      None of 18 patients who were followed clinically for a median of 39.5 months
      (range 17-84 months) experienced rebleeding. CONCLUSION: Even tiny ruptured ACoA
      aneurysms can be safely treated by EVT by expert neurointerventionalists using
      advanced techniques.

PMID- 18330520
TI  - Manganese supplementation improves mineral density of the spine and femur and
      serum osteocalcin in rats.
AB  - The effect of manganese (Mn) supplementation on bone mineral density (BMD) and
      bone metabolism parameters was determined in ovariectomized Sprague-Dawley rats.
      Rats were divided into four groups (OVX, OVX+Mn, sham, sham+Mn) and fed with
      different intake levels of manganese (adequate 0.001% Mn, supplementation 0.01%
      Mn) for 12 weeks. BMD of the lumbar vertebrae, femur, and tibia were
      significantly lowered in ovariectomized rats compared to the sham group. In
      addition, BMD of the lumbar vertebrae was significantly increased by Mn
      supplementation in the sham groups. Serum C-telopeptide cross-links of type I
      collagen (CTx), bone resorption biomarker, alkaline phosphatase (ALP), and bone
      formation biomarkers were not significantly different among the four groups.
      However, serum osteocalcin, a more sensitive bone formation biomarker, was
      significantly increased by Mn supplementation. To summarize, Mn supplementation
      resulted in increased BMD and bone formation. Based on our findings, more
      research is needed to better understand the effects of manganese supplementation
      on bone formation and resorption.

PMID- 18330521
TI  - Treatment of type 2 diabetes: a structured management plan.
AB  - The prevalence of type 2 diabetes is rising dramatically - largely due to the
      greater consumption of calorie-rich food combined with increasingly sedentary
      lifestyles - and this is set to double by 2030. Adequate management of the
      disease is vital to reduce the incidence of severe and life-threatening
      complications that arise as a consequence of diabetes. Current guidelines for the
      management of blood glucose levels have set target glycosylated haemoglobin
      (HbA(1c)) levels to <7.5%, a figure that many people do not achieve with current
      treatment strategies, highlighting a need for a simple, effective approach to
      diabetes treatment to improve glycaemic control. Recently, an algorithm for the
      initiation and adjustment of therapy in type 2 diabetes has been put forward in a
      consensus statement, which offers a structured approach to disease management. A
      step-wise plan for type 2 diabetes treatment, from the point of initial diagnosis
      to the initiation and adjustment of insulin therapy, aims to achieve glycaemic
      control and reduce the massive healthcare, economic and social consequences of
      the disease.

PMID- 18330522
TI  - Do subjective memory complaints predict senile Alzheimer dementia?
AB  - Many elderly complain about their memory and undergo dementia screening by the
      Mini-Mental State Examination (MMSE). While objective memory impairment always
      precedes Alzheimer dementia (AD) it is unclear whether subjective memory
      complaints are predicting AD. We tried to answer this question in a prospective
      cohort study. The 75-years old non-demented inhabitants of Vienna-Transdanube
      were investigated for conversion to AD after 30 months. The predictive value of
      subjective memory complaints was analysed in two groups: subjects with high MMSE
      score (28-30) and subjects with low MMSE-score (23-27). Only in subjects with
      high MMSE univariate analyses showed an association between subjective memory
      complaints and incident AD. In both groups the verbal memory test was the main
      predictor of AD in multivariate analyses. We suggest to perform memory testing in
      subjects complaining about memory irrespective of their performance in a
      screening procedure like the MMSE.

PMID- 18330523
TI  - Sexuality in Huntington's disease.
AB  - Sexuality and partnership have an important influence on the quality of life of
      patients with chronic disorders. There are just a few studies in literature about
      sexuality in Huntington's disease which conclude that up to 85% men and up to 75%
      of women experience high levels of sexual problems, most of them having prevalent
      symptoms of a hypoactive sexual disorder but also increased sexual interest and
      paraphilia were found. There is no evidence that sexual dysfunction is mainly a
      specific symptom of HD and may be associated with the specific brain lesion
      itself or if it is chiefly related to the psychosocial factors caused by the
      steadily worsening of the disease. Further studies should focus on asymptomatic
      patients to explore sexual changes preceding neurological and motor symptoms and
      should incorporate partners to objectify sexual distinctive features.
      Investigations on the context of sexual dysfunction with depression, irritability
      and dementia symptoms are needed to better understand reasons for sexual changes
      in HD. Treatment options for HD patients with sexual disorder are only reported
      sporadically, guidelines can only be obtained from non-HD patients and further
      research is needed.

PMID- 18330524
TI  - Structural neuroimaging of the basal ganglia in schizophrenic patients: a review.
AB  - The basal ganglia structures have quickened interests in schizophrenia research
      for several reasons: On the one hand, schizophrenic patients are successfully
      treated with neuroleptics acting on dopamine receptors, which are highly
      concentrated in the basal ganglia structures. On the other hand, basal ganglia
      play an important role in higher cognitive functions such as attention, working
      memory and goal-directed behavior, which are impaired in schizophrenia. Magnetic
      resonance imaging allows non-invasive in vivo volumetric measurement of these
      brain structures. In this review, we studied all available papers on MRI research
      of the basal ganglia in schizophrenic patients. We found a possibly decreased
      caudate volume in first-episode schizophrenic patients, whereas studies on
      chronic patients mostly reveal volume increases in caudate, putamen and pallidum.
      Data from longitudinal studies suggest on the one hand that typical and atypical
      neuroleptics may produce different effects on brain morphology and on the other
      hand, that these changes are dynamic and might be reversible. Further studies are
      warranted for a better understanding of the mechanisms, which may lead to
      structural basal ganglia abnormalities, with medication effects demanding
      particular attention.

PMID- 18330525
TI  - The prevalence of tick-borne encephalitis in the region of West Bohemia (Czech
      Republic) between 1960-2005.
AB  - Between 1960-2005, 1,621 cases of tick-borne encephalitis were confirmed by
      laboratory testing in the region of West Bohemia (now the regions of Pilsen and
      Karlovy Vary) which represents a rate of infection of 4.1 per 100,000 inhabitants
      per year. The highest infection rate was established in men aged 20-24 and women
      aged 45-54. Over the monitored years, there was a significant shift of the
      maximum infection rate into an older age group. Currently, it is the 45-64 age
      group which carries the highest rate of infection. Of the identified disease
      cases, 12 were lethal, which represents 0.7% of the total. Over the years, the
      risks of transmission in particular areas of the region have changed. The highest
      infection rate is currently in the district of Klatovy (21.7 per 100,000
      inhabitants per year). Of the total number, only two cases were contracted
      outside the Czech Republic (Slovakia and Austria). In 4.8% cases, the patient's
      anamnesis showed data on the consumption of non-pasteurized milk. 3.0% of
      infections probably originated as a result of professional exposure. Over the
      years, the season of infection has extended. Presently, the transmission can
      occur anytime between March and November. According to official data, only 6.7%
      of the population in the Pilsen district has been vaccinated so far. The low
      percentage of vaccinated cases may, however, in no way influence the unfavorable
      epidemiological situation regarding tick-borne encephalitis.

PMID- 18330526
TI  - [Subcutaneous interferon-beta-1a in the treatment of multiple sclerosis].
AB  - During the last 10 years recombinant interferon-beta-1a administered
      subcutaneously has been the subject of several clinical trials in relapsing
      remitting multiple sclerosis (RRMS), in secondary progressive MS (SPMS), as well
      as in clinically isolated syndromes. All of them met the criteria of evidence
      level class I. Consistent evidence for moderate immunomodulatory effects on
      clinical parameters of disease activity was gained, and even higher efficacy of
      IFN-beta-1a sc. on MRI activity of multiple sclerosis was proven. Indirect
      evidence confirmed the hypothesis of a dose-response curve for IFN-beta-1a
      formulations in MS. The higher efficacy of IFN-beta-1a 44 microg sc. TIW,
      however, also includes more adverse events such as injection site reactions, flu
      like symptoms and a moderate immunogenicity. Current evidence does not allow a
      recommendation of IFN-beta-1a sc. as most effective first line therapy, because
      also the individual patient's choice in the route of administration and long-term
      effects of neutralizing antibodies to IFN-beta-1a sc. must be taken into account.
      In the long-term, IFN-beta-1a showed a beneficial safety-tolerability profile
      with 50 % of patients sticking to the initial immunomodulatory treatment. There
      were no teratogenic effects, IFN-beta-1a sc. did not enhance depressive symptoms.
      Data on inhibition of the progression of disease, however, remained inconclusive.
      Probable beneficial effects of IFN-beta-1a sc. on cognitive function or "chronic
      fatigue" have not been investigated yet.

PMID- 18330527
TI  - [Lifestyle drugs in medicine].
AB  - Lifestyle drugs have become an important new group of medications, which are
      taken by healthy people to increase the individual well-being and quality of
      life. Nootropics, psychopharmaceuticals, hormones and "ecodrugs" are today the
      main groups. The wish for eternal youth, beauty and potency is central, and
      lifestyle medications are also requested to influence cosmetic findings, which
      are usually simply a result of the natural aging process. Lifestyle drugs seem to
      be harmless, but the physician must pay attention to possible abuse, side
      effects, risks and complications. Additionally, however, lifestyle drugs are also
      frequently used by patients suffering from emotional disorders such as somatoform
      disorders. Medicalization of physiological life is then expected to solve
      psychosocial problems, but without success. The use of lifestyle medications in
      somatoform disorders is contraindicated and psychotherapy or
      psychopharmacological treatment come first. With this overview article, we would
      like to make an update of new lifestyle drugs.

PMID- 18330528
TI  - The use of Duloxetine in the treatment of male stress urinary incontinence.
AB  - Stress urinary incontinence (SUI) is a known complication after prostate surgery.
      To date no pharmacologic treatment is available. Currently Duloxetine, a
      serotonin and norepinephrine reuptake inhibitor, is available for women with SUI.
      This study investigates the effect of Duloxetine on men with SUI after prostate
      surgery. 56 patients were included in our study. 49 after radical prostatectomy
      and 7 after TURP. All patients were initially treated with pelvic floor
      exercises. Thereafter 40 mg Duloxetine was administered twice daily. When taking
      Duloxetine, the average use of incontinence pads decreased from 3.3 to 1.5 per
      day. 14 patients needed no and 18 a single pad per day. Most patients reported
      mild and temporary side effects, 13 patients assessed them to be moderate and 9
      being severe. The results of this off-label use show that Duloxetine is effective
      in men with SUI after prostate surgery even if standard pelvic floor exercises
      have failed.

PMID- 18330529
TI  - NIMRA-survey: NSAIDs impact on mortality. Results of an Austrian Survey in 2006.
AB  - This survey is based on a sample of over two thousand patients who were in the
      first eight months of the year 2006 hospitalised due to a diagnosis of coronary
      heart disease (CHD) or rheumatic diseases (RD). Their demographic, anamnestic
      data were assessed according to a prospectively defined analysis plan together
      with the associated mortality. The main survey questions--whether the data
      suggest an association between rheumatism as compared to CHD and mortality and
      which conclusions with respect to NSAID (non-steroidal anti-inflammatory drug)
      consumption can be drawn in this pilot project--can be answered with some degree
      of statistical robustness bearing in mind the sampling uncertainties and the
      omnipresent fuzziness of medical data including mortality. Rheumatism is
      generally associated with a lower risk of death (1%) as compared to CHD patients
      with a death risk of 3% (p < 0.01). As there are many confounding risk factors
      which show statistically highly significant effects and might be associated with
      substantial interactions on the mortality outcome it seems advisable to interpret
      the available data with caution and take this as the main results of a survey
      which is characterised mainly by its pilot nature. Additional research in this
      area with more sophisticated tools and based on much larger samples is judged to
      provide final and conclusive epidemiologic evidence. For the time being NSAIDs
      did not imply any relevant increases in mortality in RD or CHD patients as
      compared to patients who were not prescribed NSAIDs. Coronary heart diseases
      constitute a relevant and significant prognostic factor for an increased
      mortality as compared to rheumatic diseases.

PMID- 18330530
TI  - [Systematic reviews and meta-analysis].
AB  - Over the past years, systematic reviews and meta-analyses have led to significant
      changes in clinical medicine and health policy. To date, they can be viewed as
      the most objective instruments to answer clinical as well health policy
      questions. In addition, systematic reviews are an important tool to synthesize
      the enormous amount of new medical knowledge into a manageable format.
      Nevertheless, the methodological quality of published systematic reviews and meta
      analyses varies and biased results can be misleading. Therefore, it is important
      for readers of systematic reviews to critically evaluate the underlying methods,
      to be able to assess the validity of their findings. This manuscript is part of a
      methods series of the Wiener Medizinische Wochenschrift. It summarizes the
      methodological hallmarks of systematic reviews and meta-analyses to provide
      readers with the methodological background necessary to critically evaluate
      systematic reviews and meta-analyses.

PMID- 18330531
TI  - [Negative-pressure pulmonary edema after general anaesthesia. Imaging diagnostic
      procedure].
AB  - Negative-pressure pulmonary edema is not a rare complication, e.g. in general
      anaesthesia and the diagnosis is made predominantly by clinical findings. When
      clinical findings are not clear radiology is necessary. This case report with
      detailed radiologic diagnostics, including follow-up, shows which radiologic
      signs are important for the clinical assessment to obtain a precise diagnosis and
      to start an adequate therapy.

PMID- 18330532
TI  - [Diagnosis and therapy of stool incontinence].
AB  - Incontinence may have different causes. First it is necessary to diagnose any
      underlying muscular defects. Neurologic lesions and coordinative disturbances
      should also be excluded. A great variety of methods are available for treatment.
      In fact conservative therapy alone will very often be successful. In all
      traumatic lesions of the sphincter muscle, surgical reconstruction is the method
      of choice if the defect is not too large. In cases of extensive sphincter
      destruction, an artificial anorectal sphincter implant or dynamic graciloplasty
      may be options. In all cases with no or only small muscular defects, sacral nerve
      stimulation should be offered to the patient. Plicating techniques such as pre-
      or postanal repair have lost their therapeutic attractiveness at present.
      Therefore in any case of incontinence, the correctly structured stoma still has a
      place. To date it is not possible to confirm how much new methods such as bulking
      agents may contribute to the treatment of incontinence.

PMID- 18330533
TI  - [Significance of computed tomography evaluation before revision stapes surgery].
AB  - BACKGROUND: Stapedectomy and, more recently, stapedotomy have been widely
      accepted as the primary surgical techniques to improve conductive hearing in
      patients suffering from otosclerosis. Unsuccessful outcomes are infrequent, but
      revision surgery may become necessary. We have analyzed the value of computed
      tomography (CT) scanning following unsuccessful stapes surgery. PATIENTS AND
      METHODS: In a total of 37 CT scans, the depth of insertion, angle between
      prosthesis and footplate, location of prosthesis within the oval niche,
      visibility of the prosthesis, dehiscence of the superior semicircular canal, and
      extent of otospongiotic foci were evaluated and compared with the audiometric
      results. RESULTS: There was no significant correlation between CT parameters and
      audiologic results, except for patients with cochlear otosclerosis or lateral
      dislocation of the piston. One previously unknown dehiscence of the superior
      semicircular canal was diagnosed. Otospongiotic foci were seen in 13 ears (35%).
      CONCLUSION: Displacements of the stapes piston and rare causes for an
      insufficient result, such as a dehiscence of the superior semicircular canal, can
      be diagnosed accurately by CT. However, correlation between the audiologic
      results and the findings on CT scans was possible in only a few cases.
      Nevertheless, CT scans provide additional information for surgical planning in
      revision stapes surgery and may become increasingly important to reduce
      unanticipated intraoperative risks; they may even guide the surgeon not to
      perform unnecessary revision surgeries.

PMID- 18330534
TI  - [New oral antidiabetic agents--clinical perspectives].
AB  - In recent years new pharmacological agents have emerged, which enable us to widen
      the spectrum of diabetes management based on clear pathophysiological concepts.
      One should first of all mention the DPP4-inhibitors and the incretin mimetics,
      which have the potential of restoring the incretin effect in patients with type 2
      diabetes mellitus. Moreover, it has been shown that the agent rimonabant, which
      was first used in order to achieve weight reduction, also contributed to the
      significant improvement of metabolic syndrome's parameters. Recent studies have
      shown that the dual alpha/gamma-PPAR-agonists have serious adverse effects. The
      thiazolidinediones (glitazones) significantly improve insulin sensitivity,
      diminish fat accumulation in the liver and increase circulating levels of
      adiponectin. Various adverse effects of glitazones have been described in recent
      studies. In the near future one should await the discovery of more oral
      antidiabetic agents acting through modulation of important enzymes in glucose
      metabolism and transport pathways.

PMID- 18330535
TI  - Common volatiles are major attractants for neonate larvae of the specialist flea
      beetle Altica koreana (Coleoptera: Chrysomelidae).
AB  - Olfactory stimuli play an important role in the host searching of larval
      phytophagous insects. Previous studies indicate that larvae that have to find
      feeding sites after hatching are generally attracted to host volatiles. However,
      there are few studies on the olfactory responses of neonate larvae to host
      volatiles in cases when those larvae hatched on the host plant. In the present
      study, we determined the olfactory responses of neonate larvae of the specialist
      flea beetle, Altica koreana Ogloblin, to host and six non-host plants, using a
      static-air "arena." Larvae responded significantly to the host plant Potentilla
      chinensis Ser. and five of six non-host plants, compared to the control. Larvae
      did not prefer the host plant over the non-host plants (except Artemisia sp.)
      when offered a choice. Additionally, odours of a non-host plant, which were
      unattractive to neonate larvae, may have masked the attractive odour of the host
      plant. These results indicate that common volatiles can play a major role in
      attracting larvae of this specialist to plants, but attraction to such odours may
      not be the major mechanism of host choice.

PMID- 18330536
TI  - Autumn leaf colouration: a new hypothesis involving plant-ant mutualism via
      aphids.
AB  - Several recent hypotheses on the adaptive significance of autumn leaf colours
      have focused on specialist aphids. However, these hypotheses have overlooked
      several factors: the preferential investment by healthy vigorous trees in growth
      rather than defence against herbivores, variation among aphid species in their
      responses to bright autumn leaves and plant defences and the occurrence of
      tritrophic interactions in tree crowns. I incorporate these factors into a
      hypothesis that autumn leaf colours signal tree quality to myrmecophilous
      specialist aphids, with the aphids, in turn, attracting aphid-tending ants during
      the following spring, and the ants defending the trees from other aphids and
      herbivores. Therefore, bright autumn leaves may have adaptive significance,
      attracting myrmecophilous specialist aphids and their attending ants and, thus,
      reducing herbivory and competition among aphids.

PMID- 18330537
TI  - Costs of female odour in males of the parasitic wasp Lariophagus distinguendus
      (Hymenoptera: Pteromalidae).
AB  - The display of female traits by males is widespread in the animal kingdom. In
      several species, this phenomenon has been shown to function adaptively as a male
      mating strategy to deceive sexual rivals (female mimicry). Freshly emerged males
      of the parasitic wasp Lariophagus distinguendus (Hymenoptera: Pteromalidae) are
      perceived by other males as if they were females because of a very similar
      composition of cuticular hydrocarbons which function as a sex pheromone in this
      species inducing courtship behaviour in males. Within 32 h, however, males
      deactivate the pheromone and are no longer courted by other males. In this paper,
      behavioural experiments were performed to test hypotheses on potential costs and
      benefits associated with the female odour in young males. We did not find any
      benefits, but demonstrated that young males were significantly more often
      outrivaled in male-male contests when competing with two older males for a
      female. Also, young males were significantly more often mounted in homosexual
      courtship events during these contests. Thus, display of female traits by males
      is not necessarily beneficial, and in fact, can be disadvantageous. We suggest
      that these costs have favoured the evolution of the pheromone deactivation
      mechanism in L. distinguendus males. The function of cuticular hydrocarbons as a
      female courtship pheromone in L. distinguendus might have evolved secondarily
      from a primary function relevant for both genders, and the deactivation of the
      signal in males might have caused a shift of specificity of the chemical signal
      from the species level to the sex level.

PMID- 18330538
TI  - Global information sampling in the honey bee.
AB  - Central to the question of task allocation in social insects is how workers
      acquire information. Patrolling is a curious behavior in which bees meander over
      the face of the comb inspecting cells. Several authors have suggested it allows
      bees to collect global information, but this has never been formally evaluated.
      This study explores this hypothesis by answering three questions. First, do bees
      gather information in a consistent manner as they patrol? Second, do they move
      far enough to get a sense of task demand in distant areas of the nest? And third,
      is patrolling a commonly performed task? Focal animal observations were used to
      address the first two predictions, while a scan sampling study was used to
      address the third. The results were affirmative for each question. While
      patrolling, workers collected information by performing periodic clusters of cell
      inspections. Patrolling bees not only traveled far enough to frequently change
      work zone; they often visited every part of the nest. Finally, the majority of
      the bees in the middle-age caste were shown to move throughout the nest over the
      course of a few hours in a manner suggestive of patrolling. Global information
      collection is contrary to much current theory, which assumes that workers respond
      to local information only. This study thus highlights the nonmutually exclusive
      nature of various information collection regimes in social insects.

PMID- 18330539
TI  - [Elective termination of respiratory therapy in amyotrophic lateral sclerosis].
AB  - BACKGROUND: Due to the growing use of artificial respiration in amyotrophic
      lateral sclerosis (ALS), physicians are increasingly confronted with patients
      seeking discontinuation of therapy. Yet there are few systematic investigations
      of the withdrawal of ventilation therapy. PATIENTS AND METHODS: In a
      retrospective investigation of nine German ALS patients, clinical data were
      recorded from the discontinuation of noninvasive ventilation (n=4) and mechanical
      ventilation (n=5). RESULTS: In cases of residual spontaneous breathing,
      intensified symptom control of dyspnea and anxiety was possible with intravenous
      morphine sulfate at a low dose rate (10 mg/h) but high cumulative dose (185-380
      mg). The terminal phase after removing the mask was protracted (22:10 h to 28:00
      h). In cases of minimal or absent spontaneous breathing the disconnection was
      realized in deep sedation, which required a moderate total dose of morphine
      sulfate (120 mg) but a high dosage rate (up to 300 mg/h). The terminal phase in
      deep sedation was short (15-80 min). CONCLUSION: The elective termination of
      ventilation requires differentiated pharmacologic palliative care. More
      controlled studies are required in order to establish evidence-based guidelines
      for the termination of ventilation.

PMID- 18330540
TI  - [The Erlangen examination. An alternative to multiple choice testing for German
      neurology students].
AB  - BACKGROUND: With the latest revision of the German Medical Licensing Regulation
      in 2002, educating faculties gained more freedom in the organisation and
      assessment of trainees. The Erlangen Neurological Exam Structured (ERNEST) is an
      alternative for assessing competency in clinical knowledge at the end of the
      neurological general education. The answers must be given in written, short essay
      format. METHOD: The students (mostly 5th year of medical education) underwent the
      ERNEST including eight sections with ten to 15 questions each and the MC
      examination as had been applied earlier. The results were given in percentage
      scores. The examination was evaluated by a questionnaire using Likert scales.
      RESULTS: A total of 128 students (81 women, 47 men) with a mean age of 25.3 years
      (range 22-33) completed their initial training by the exam. The mean score was
      69.6% in the ERNEST and 73.4% in the MC part (P<0.001). Of the students 12.5% in
      ERNEST and 11.7% in the MC (nonsignificant) failed to reach the projected score
      of 60% to pass the exam. Correlation between the ERNEST and MC results was
      significant, with r=0.784 (Pearson's coefficient, P<0.001). The students
      evaluated the aspects innovation, length, format, clarity of the tasks, closeness
      to reality, and compatibility with general physician's practice as predominantly
      positive. CONCLUSION: The ERNEST is a viable alternative form of assessment as
      compared to the conventional MC exam. The basic quantitative parameters of the
      assessment comply with the requirements of medical assessments. The students
      evaluated ERNEST as mainly positive.

PMID- 18330541
TI  - [Use of an outpatient treatment center for cannabis abuse].
AB  - BACKGROUND: There has been an increase of cannabis-related disorders in Germany
      during the last 10 years. According treatments are being established, however
      little is known about the treatment populations. METHODS: The population of an
      outpatient treatment program for diagnosis and therapy of cannabis-related
      disorders was investigated using a structured interview (based on EuropASI, SCID
      I) regarding sociodemographic variables, history of addiction, consumption
      patterns, and psychiatric comorbidity. RESULTS: The 90 patients studied had a
      mean age of 27.5+/-6.6 years; 82% were male. They claimed averages of cannabis
      consumption for 11+/-7 years and current amount at 1.9 g per day. Alcohol
      problems were also common in this sample. High percentages were shown regarding
      unemployment, living alone, and problems with the law. Comorbid psychiatric
      disorders were diagnosed in 42% of patients. CONCLUSIONS: The patients were
      chronic users of cannabis with extensive psychosocial problems. Therapy of
      cannabis-related disorders should therefore include treatment for comorbidities
      and social care besides the treatment for addictive behavior.

PMID- 18330542
TI  - Diabetic podopathy--no thanks!

PMID- 18330543
TI  - Ab initio fragment molecular orbital study of ligand binding to human
      progesterone receptor ligand-binding domain.
AB  - We applied the fragment molecular orbital (FMO) method, which enables total
      electronic calculations of large molecules at ab initio level, to the evaluation
      of binding affinities between the human progesterone receptor ligand-binding
      domain (PR LBD) and various steroidal ligands. The FMO calculations were
      performed on the entire structure of the PR LBD, which is composed of
      approximately 4,100 atoms. Our computational binding energies of PR LBD/ligand
      complexes agreed well with experimental binding affinities (r=0.909). Interaction
      energies between each ligand and specific amino acid residues were also obtained
      from the FMO calculations. The principal residues involved in the interactions
      with these ligands were Arg766 and Asn719, with some additional contribution by
      Gln725. The main factor determining differences in binding affinity of the
      various ligands was not interactions with particular residues, but with the
      binding-site residues closest to the ligand. The interfragment interaction energy
      analysis is proving to be a useful method for gaining detailed information on
      ligand binding.

PMID- 18330544
TI  - Effects of tryptophan deficiency on prepulse inhibition of the acoustic startle
      in rats.
AB  - RATIONALE: Serotonin (5-HT) plays a key role in the pathophysiology of psychotic
      disorders, presumably through a modulation of dopamine (DA) transmission.
      Reduction of 5-HT signaling has been suggested to enhance dopaminergic responses
      in animal models of psychosis. An intriguing naturalistic strategy to reduce 5-HT
      brain content is afforded by the dietary restriction to its precursor, l
      tryptophan (TRP). OBJECTIVE: We investigated the impact of a TRP-deficient diet
      in rats on the prepulse inhibition of the startle (PPI), a measure of
      sensorimotor gating which is typically impaired by psychotomimetic substances.
      MATERIALS AND METHODS: After either short-term (6 h) or long-term (14 days) TRP
      deprivation, rats were tested for startle reflex and PPI. Moreover, we assessed
      the impact of both TRP deprivation regimens on PPI reduction induced by the
      psychotomimetic substance d-amphetamine (AMPH). RESULTS: Both TRP-deficient
      regimens failed to significantly affect PPI responses. However, chronic, but not
      short-term, TRP-deficient diet induced a significant sensitization to the effects
      of AMPH (1.25-2.5 mg/kg, subcutaneous). The enhanced predisposition to PPI
      disruption elicited by prolonged TRP deprivation was completely reversed 24 h
      after reinstatement of TRP in the diet, as well as pretreatment with
      antipsychotic drugs haloperidol (0.1 mg/kg, intraperitoneal) and clozapine (5
      mg/kg, intraperitoneal), which exert their therapeutic action mostly through
      blockade of DA D(2) receptors. CONCLUSIONS: The present results confirm and
      extend previous findings on the impact of serotonergic signaling in the
      modulation of DA transmission in schizophrenia and point to chronic TRP
      deprivation as a potential model of environmental manipulation that may produce a
      sensitization to psychotic-like symptoms induced by dopaminergic activation.

PMID- 18330545
TI  - Dysregulation of emotional response in current and abstinent heroin users:
      negative heightening and positive blunting.
AB  - OBJECTIVE: Evidence suggests that abstinent opioid users have abnormal emotional
      response to natural reinforcing stimuli, but little is known about the emotional
      response of subjects currently using heroin. Abnormal emotional experience could
      underlie poor sensitivity to negative events related to heroin use and reduced
      ability to consider alternative reinforcers to help overcome addiction. In this
      paper, we will assess the subjective response of current and abstinent heroin
      users exposed to emotionally competent positive and negative stimuli. MATERIALS
      AND METHODS: We administered the "Clinical Instrument for Emotional Response
      Evaluation" (including neutral, pleasant, and unpleasant images from the
      International Affective Picture System) to 22 current opioid users enrolled in a
      clinical trial using controlled prescribed heroin and 41 abstinent opioid users
      enrolled in residential treatment. The dependent variable was their subjective
      response to the images measured with the Self-Assessment Manikin, a scale
      designed to rate the International Affective Picture System (IAPS) images in the
      three dimensions of emotion: valence, arousal, and dominance. We compared these
      ratings with IAPS normative values for healthy participants. RESULTS: Significant
      group x emotional condition interactions were found in the arousal dimension.
      Post-hoc tests showed that compared to healthy participants, both current and
      abstinent heroin users had greater emotional response to neutral images and lower
      response to pleasant images. Furthermore, current opioid users had higher
      emotional response to unpleasant images when compared to healthy participants and
      lower response to pleasant images when compared to abstinent users. CONCLUSIONS:
      Current opioid users have abnormal emotional experience, characterized by
      heightened response to unpleasant stimuli and blunted response to pleasant
      stimuli.

PMID- 18330546
TI  - LC-MS-based procedures for monitoring of toxic organophosphorus compounds and
      verification of pesticide and nerve agent poisoning.
AB  - Organophosphorus compounds (OPCs) are used worldwide as, e.g., flame retardants,
      plasticizers, and pesticides and remaining stockpiles of OPC nerve agents are
      present in military arsenals. These OPCs exhibit acute and potential chronic
      toxicity to man, the environment, and biota thus emphasizing the need for
      efficient analytical procedures to monitor potential risk to health. Therefore,
      this review discusses LC-MS-based procedures for OPC detection, addressing sample
      preparation, separation, ionization, and detection in comprehensive detail. For
      sample preparation conventional liquid-liquid extraction (LLE) and diverse solid
      phase extraction (SPE) procedures are still used most frequently. Nevertheless,
      during the last three years a number of sophisticated novel methods have been
      introduced. Solid-phase microextraction (SPME), stir-bar-sorptive extraction
      (SBSE), membrane-assisted solvent extraction (MASE), and specifically designed
      molecularly imprinted polymers (MIP) exhibit high potential for frequent use in
      the future. Additional emphasis in this review is dedicated to the quite young
      history and current progress in ionization and MS detection of OPCs. The number
      of relevant published LC-MS reports has tripled in the last five years. This is
      especially due to the proliferating use of electrospray ionization (ESI),
      nowadays an indispensable and reliable tool for LC-MS coupling. LC-MS is becoming
      an appropriate complementary or replacement method for the more traditional GC-MS
      methods, and not only for non-volatile, hydrophilic, and ionic OPCs. The last
      section of this review covers recent approaches for verification of OPC
      poisoning. LC-MS-MS detection of phosphylated peptides generated from inhibited
      circulating serum butyrylcholinesterase (BChE) by valuable proteomics techniques
      enables proof of intoxication on the molecular level. Therefore, this review
      gives a comprehensive overview on the status quo of LC-MS-based OPC analysis in
      respect of both technical progress and relevant applications.

PMID- 18330547
TI  - Acute anoxia stimulates proliferation in adult neural stem cells from the rat
      brain.
AB  - Hypoxic-ischemic damage is a major challenge for neuronal tissue. In the present
      study, we investigated the effects of anoxia and glucose deprivation on adult
      neural stem cells (NSCs) in vitro. We assessed glucose deprivation, anoxia and
      the combination of the latter separately. After 24 h of anoxia, cell numbers
      increased up to 60% compared to normoxic controls. Whereas nearly all normoxic
      cells incorporated the mitotic marker BrdU (99%), only 85% of the anoxic cells
      were BrdU-positive. Counting of interphase chromosomes showed 8-fold higher cell
      division activity after anoxia. The number of necrotic cells doubled after anoxia
      (14% compared to 7% after normoxia). Apoptosis was measured by two distinct
      caspases assays. Whereas the total caspase activity was reduced after anoxia,
      caspase 3/7 showed no alterations. Glucose deprivation and oxygen glucose
      deprivation both reduced cell viability by 56 and 53%, respectively. Under these
      conditions, total caspases activity doubled, but caspase 3/7 activity remained
      unchanged. Erythropoietin, which was reported as neuroprotective, did not
      increase cell viability in normoxia, but moderately under oxygen glucose
      deprivation by up to 6%. Erythropoietin reduced total caspase activity by nearly
      30% under all the conditions, whereas caspase 3/7 activity was not affected. Our
      results show that anoxia increases proliferation and viability of adult NSCs,
      although a fraction of NSCs does not divide during anoxia. In conclusion, anoxia
      increased cell viability, cell number and proliferation in NSCs from the rat
      brain. Anoxia turned out to be a highly stimulating environmental for NSCs and
      NSCs died only when deprived of glucose. We conclude that the availability of
      glucose but not of oxygen is a crucial factor for NSC survival, regulating
      apoptotic pathways via caspases activity other than the caspases 3/7 pathway.
      Therefore, we conclude that NSCs are dying from glucose deprivation, not from
      hypoxic-ischemic damage.

PMID- 18330548
TI  - Interaction of paired cortical and peripheral nerve stimulation on human motor
      neurons.
AB  - This paper contrasts responses in the soleus muscle of normal human subjects to
      two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired
      transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10-25
      ms strongly facilitated the motor evoked potential (MEP) produced by the second
      stimulus. In contrast, paired TN stimulation produced a depression of the reflex
      response to the second stimulus. Direct activation of the pyramidal tract did not
      facilitate a second response, suggesting that the MEP facilitation observed using
      paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP.
      Since the TN stimulus depressed both inputs, the mechanism is probably post
      synaptic, such as afterhyperpolarization of motor neurons. Presynaptic
      mechanisms, such as homosynaptic depression, would only affect the pathway used
      as a conditioning stimulus. When TN and TMS pulses were paired, the largest
      facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for
      summation of the two pathways at the level of the spinal motor neurons. A later,
      smaller facilitation occurred when a single TN stimulus preceded TMS by 50-60 ms,
      an interval that allows enough time for the sensory afferent input to reach the
      sensory cortex and be relayed to the motor cortex. Other work indicates that
      repetitively pairing nerve stimuli and TMS at these intervals, known as paired
      associative stimulation, produces long-term increases in the MEP and may be
      useful in strengthening residual pathways after damage to the central nervous
      system.

PMID- 18330549
TI  - Dynamics model for analyzing reaching movements during active and passive torso
      rotation.
AB  - We have developed an inverse dynamics model of unrestrained natural reaching
      movements. Such movements are usually not planar and often involve complex
      deformation of the shoulder girdle as well as rotary and linear torso motion. Our
      model takes as its input kinematic data about the positions of the finger, wrist,
      elbow, left and right acromion processes, and the sternum and produces the
      torques and forces developed at the shoulder, elbow, and wrist joints. The model
      can also be used to simulate the consequences of introducing passive torso
      rotation or linear acceleration on arm movements and to simulate the consequences
      of applying mechanical perturbations to the reaching limb. It separately
      quantifies the contributions of inertial forces resulting from torso rotation and
      translation. In experimental paradigms involving arm movements, different dynamic
      components can be present such as active or passive torso rotation and
      translation, external forces and Coriolis forces. Our model provides a means of
      evaluating the different sources of force and the total muscle force needed to
      control the trajectory of the arm in their presence.

PMID- 18330550
TI  - Kinetic analysis of arm reaching movements during voluntary and passive rotation
      of the torso.
AB  - Reaching movements made to targets during exposure to passive constant velocity
      rotation show significant endpoint errors. By contrast, reaching movements made
      during voluntary rotation of the torso are accurate. In both cases, as a
      consequence of the simultaneous motion of the arm and the torso, Coriolis forces
      are generated on the arm tending to deflect its path. Our goal in the present
      paper was to determine whether during voluntary torso rotations arm movement
      accuracy is preserved by feed forward compensations for self-generated Coriolis
      forces. To test this hypothesis we analyzed and quantified the contribution of
      torso rotation and translation to arm dynamics and compared the kinematics and
      kinetics of pointing movements during voluntary and passive torso rotation.
      Coriolis torques at the shoulder increase nearly sixfold in voluntary turn and
      reach movements relative to reaches made without torso rotation, yet are equally
      accurate. Coriolis torques during voluntary turn and reach movements are more
      than double those produced by reaching movements during passive body rotation at
      60 degrees /s. Nevertheless, the endpoints of the reaches made during voluntary
      rotation are not deviated, but those of reaches made during passive rotation are
      deviated in the direction of the Coriolis forces generated during the movements.
      We conclude that there is anticipatory pre-programmed compensation for self
      generated Coriolis forces during voluntary torso rotation contingent on intended
      torso motion and arm trajectory.

PMID- 18330551
TI  - Neurotoxic lesions of the medial prefrontal cortex or medial striatum impair
      multiple-location place learning in the water task: evidence for neural
      structures with complementary roles in behavioural flexibility.
AB  - This series of experiments assessed the effects of neurotoxic damage to either
      the medial prefrontal cortex or the medial striatum on the acquisition of
      multiple-location place learning in the water task. During training, normal
      subjects learn to search for a new hidden platform location at the beginning of
      each training session and to continue to swim to that location until the end of
      training during that session. By the end of training, normal subjects show one
      trail place learning in which they find the new location on the first trial and
      swim directly to that location on the second swim. Rats with damage to either the
      medial prefrontal cortex or dorso-medial striatum showed deficits in learning to
      swim to the new location each day. These deficits were interpreted as impairments
      in behavioural flexibility. The lesion-induced impairment was not caused by
      perseverative errors but was manifested in an inability to rapidly acquire a new
      spatial position in conflict with the previous position. Interestingly, the
      subjects from both lesion groups were able to show normal place learning and
      memory after repeated training within a session. The results were interpreted as
      suggestive of a complementary role of these neural structures in behavioural
      flexibility.

PMID- 18330552
TI  - Saccade selection when reward probability is dynamically manipulated using Markov
      chains.
AB  - Markov chains (stochastic processes where probabilities are assigned based on the
      previous outcome) are commonly used to examine the transitions between behavioral
      states, such as those that occur during foraging or social interactions. However,
      relatively little is known about how well primates can incorporate knowledge
      about Markov chains into their behavior. Saccadic eye movements are an example of
      a simple behavior influenced by information about probability, and thus are good
      candidates for testing whether subjects can learn Markov chains. In addition,
      when investigating the influence of probability on saccade target selection, the
      use of Markov chains could provide an alternative method that avoids confounds
      present in other task designs. To investigate these possibilities, we evaluated
      human behavior on a task in which stimulus reward probabilities were assigned
      using a Markov chain. On each trial, the subject selected one of four identical
      stimuli by saccade; after selection, feedback indicated the rewarded stimulus.
      Each session consisted of 200-600 trials, and on some sessions, the reward
      magnitude varied. On sessions with a uniform reward, subjects (n = 6) learned to
      select stimuli at a frequency close to reward probability, which is similar to
      human behavior on matching or probability classification tasks. When informed
      that a Markov chain assigned reward probabilities, subjects (n = 3) learned to
      select the greatest reward probability more often, bringing them close to
      behavior that maximizes reward. On sessions where reward magnitude varied across
      stimuli, subjects (n = 6) demonstrated preferences for both greater reward
      probability and greater reward magnitude, resulting in a preference for greater
      expected value (the product of reward probability and magnitude). These results
      demonstrate that Markov chains can be used to dynamically assign probabilities
      that are rapidly exploited by human subjects during saccade target selection.

PMID- 18330553
TI  - A plate holder for non-destructive testing of mesophase crystallization assays.
AB  - Here, we describe a goniometer holder to mount standard 96-well crystallization
      plates directly onto the goniometer head of an oscillation camera. This
      attachment was designed to check crystallization conditions straight from the
      crystallization plates under X-rays, and was proven to be useful for checking
      small crystals and solutions that destabilize monoolein-based lipidic cubic phase
      (LCP) crystallization experiments. A quick procedure for setting up LCP assays
      employing commercially available instruments is also reported.

PMID- 18330554
TI  - Microinjection in combination with microfluorimetry to study proton diffusion
      along phospholipid membranes.
AB  - Proton diffusion along the surface of a planar bilayer lipid membrane was
      measured by means of acid/base injection with a micropipette and recording of the
      kinetics of fluorescence changes of fluorescein-labelled lipid on the surface.
      The dimensionality of the process was assayed by fitting the kinetic curves with
      two-dimensional (2D) or three-dimensional (3D) diffusion equations. In agreement
      with Serowy et al. (Biophys J 84:1031-1037, 2003), lateral proton diffusion
      proceeded via bulk phase by means of buffer molecules as proton carriers (D = 600
      microm2/s) under the conditions of 1 mM buffer in the solution. Introduction of
      proton binding sites on the membrane surface led to the appearance of a
      considerable contribution of two-dimensional proton diffusion on the membrane
      surface with D = 1,100 mum(2)/s. The system described can be used to study the
      dependence of the proton diffusion rate on the phospholipid and protein
      composition of the membrane.

PMID- 18330555
TI  - Charge stabilization in reaction center protein investigated by optical
      heterodyne detected transient grating spectroscopy.
AB  - Photosynthetic reaction center (RC) pigment protein complex converts the free
      energy of light into chemical potential of charge pairs with extremely high
      efficiency. A transient phase in the absorption spectrum in the sub-millisecond
      time scale is expected to be especially important to examine the conformational
      gating model of the Q(A)Q(B) to Q(A)Q(B) (here Q(A )and Q(B) are the primary and
      secondary quinone type electron acceptors, respectively) electron transport.
      Essential kinetic components at few tens of microseconds scale and at around 200
      microseconds have been suggested. We investigated the conformation change of RCs
      using heterodyne detection of the laser-induced transient grating method. An
      about 25 microseconds dynamics was observed, which coincides with the one
      described by the conformational gating model and possibly related to the
      nonadiabatic intrinsic Q(A)Q(B) to Q(A)Q(B) electron transport. The relative
      intensity of this component decreased with increasing quinone concentration
      indicating an initial (P+Q(A))1 or a relaxed (P+Q(A))2 conformational substate.
      We did not find the decay component at few hundreds of microseconds time scale
      indicating that there is no large displacement in the RC structure if Q(B) is
      present. The diffusion coefficient of the RC/LDAO detergent micelles calculated
      from the kinetic component was D = 3.8 x 10(-11 ) m2/s that agrees fairly well
      with the number estimated from the Einstein-Stokes relationship, and relates to a
      hydrodynamic diameter of 11.4 nm of the RC in LDAO micellar solution.

PMID- 18330556
TI  - Water structure around dipeptides in aqueous solutions.
AB  - The bulk water structure around small peptide fragments--glycyl-L-alanine, glycyl
      L-proline and L:-alanyl-L-proline-has been determined by a combination of neutron
      diffraction with isotopic substitution and empirical potential structural
      refinement techniques. The addition of each of the dipeptides to water gives rise
      to decreased water-water coordination in the surrounding water solvent.
      Additionally, both the Ow-Ow radial distribution functions and the water-water
      spatial density functions in all of the solutions indicate an electrostrictive
      effect in the second water coordination shell of the bulk water network. This
      effect is not observed in similar experiments on the amino acid L: -proline alone
      in solution, which is one component of two of the peptides measured here.

PMID- 18330557
TI  - Evidence for a transposition event in a second NITR gene cluster in zebrafish.
AB  - Novel immune-type receptors (NITRs) are immunoglobulin-variable (V) domain
      containing cell surface proteins that possess characteristic
      activating/inhibitory signaling motifs and are expressed in hematopoietic cells.
      NITRs are encoded by multigene families and have been identified in bony fish
      species. A single gene cluster, which encodes 36 NITRs that can be classified
      into 12 families, has been mapped to zebrafish chromosome 7. We report herein the
      presence of a second NITR gene cluster on zebrafish chromosome 14, which is
      comprised of three genes (nitr13, nitr14a, and nitr14b) representing two
      additional NITR gene families. Phylogenetic analyses indicate that the V domains
      encoded by the nitr13 and nitr14 genes are more similar to each other than any
      other zebrafish NITR suggesting that these genes arose from a tandem gene
      duplication event. Similar analyses comparing zebrafish Nitr13 and Nitr14 to
      NITRs from other fish species indicate that the nitr13 and nitr14 genes are
      phylogenetically related to the catfish IpNITR13 and IpNITR15 genes. Sequence
      features of the chromosomal region encoding nitr13 suggest that this gene arose
      via retrotransposition.

PMID- 18330558
TI  - Mannose-binding lectin haplotypes influence Brucella abortus infection in the
      water buffalo (Bubalus bubalis).
AB  - A case-control study established that the haplotype pair HYA/HYA at the MBL
      (mannose binding lectin) locus of water buffalo is associated with resistance to
      Brucella abortus infection (P < 10(-7)) and the haplotype pairs LYD/LYD with
      susceptibility to the same pathogen (P < 10(-7)). The subjects included in the
      present study were tested twice-at a 1-month interval-for the presence of anti-B.
      abortus antibodies in the serum by agglutination, complement fixation and flow
      cytometry. Cases (335 subjects) included animals consistently positive to all
      these tests; controls (335 subjects) comprised animals exposed yet negative by
      the same tests. The serum from genetically resistant subjects displayed in vitro
      significantly higher antibacterial activity compared to the serum from
      genetically susceptible subjects, lending biological significance to the results
      from the association study. Inhibition of the antibacterial activity following
      heat treatment of the serum, addition of specific MBL inhibitors (EDTA, mannose,
      N-acetyl-D: -glucosamine) or anti-human MBL antiserum provide convincing evidence
      that the antibacterial activity present in the serum results from the interaction
      between MBL and B. abortus. A replication study (comprising 100 cases and 100
      controls) confirmed the results from the original study.

PMID- 18330559
TI  - Biodegradation and kinetics of aerobic granules under high organic loading rates
      in sequencing batch reactor.
AB  - Biodegradation, kinetics, and microbial diversity of aerobic granules were
      investigated under a high range of organic loading rate 6.0 to 12.0 kg chemical
      oxygen demand (COD) m(-3) day(-1) in a sequencing batch reactor. The selection
      and enriching of different bacterial species under different organic loading
      rates had an important effect on the characteristics and performance of the
      mature aerobic granules and caused the difference on granular biodegradation and
      kinetic behaviors. Good granular characteristics and performance were presented
      at steady state under various organic loading rates. Larger and denser aerobic
      granules were developed and stabilized at relatively higher organic loading rates
      with decreased bioactivity in terms of specific oxygen utilization rate and
      specific growth rate (muoverall) or solid retention time. The decrease of
      bioactivity was helpful to maintain granule stability under high organic loading
      rates and improve reactor operation. The corresponding biokinetic coefficients of
      endogenous decay rate (kd), observed yield (Yobs), and theoretical yield (Y) were
      measured and calculated in this study. As the increase of organic loading rate, a
      decreased net sludge production (Yobs) is associated with an increased solid
      retention time, while kd and Y changed insignificantly and can be regarded as
      constants under different organic loading rates.

PMID- 18330560
TI  - Multi-copy expression and fed-batch production of Rhodotorula araucariae epoxide
      hydrolase in Yarrowia lipolytica.
AB  - Epoxide hydrolases (EHs) of fungal origin have the ability to catalyze the
      enantioselective hydrolysis of epoxides to their corresponding diols. However,
      wild type fungal EHs are limited in substrate range and enantioselectivity.
      Additionally, the production of fungal epoxide hydrolase (EH) by wild-type
      strains is typically very low. In the present study, the EH-encoding gene from
      Rhodotorula araucariae was functionally expressed in Yarrowia lipolytica, under
      the control of a growth phase inducible hp4d promoter, in a multi-copy expression
      cassette. The transformation experiments yielded a positive transformant, with a
      final EH activity of 220 U/g dw in shake-flask cultures. Evaluation of this
      transformant in batch fermentations resulted in approximately 7-fold improvement
      in EH activity over the flask scale. Different constant specific feed rates were
      tested in fed-batch fermentations, resulting in an EH activity of 1,750 U/g dw at
      a specific feed rate of approximately 0.1 g/g/h, in comparison to enzyme
      production levels of 0.3 U/g dw for the wild type R. araucariae and 52 U/g dw for
      an Escherichia coli recombinant strain expressing the same gene. The expression
      of EH in Y. lipolytica using a multi-copy cassette demonstrates potential for
      commercial application.

PMID- 18330561
TI  - Cloning and characterization of a new laccase from Bacillus licheniformis
      catalyzing dimerization of phenolic acids.
AB  - A new laccase gene (cotA) was cloned from Bacillus licheniformis and expressed in
      Escherichia coli. The recombinant protein CotA was purified and showed
      spectroscopic properties, typical for blue multi-copper oxidases. The enzyme has
      a molecular weight of approximately 65 kDa and demonstrates activity towards
      canonical laccase substrates 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic
      acid) (ABTS), syringaldazine (SGZ) and 2,6-dimethoxyphenol (2,6-DMP). Kinetic
      constants KM and kcat for ABTS were of 6.5+/-0.2 microM and 83 s(-1), for SGZ of
      4.3+/-0.2 microM and 100 s(-1), and for 2,6-DMP of 56.7+/-1.0 microM and 28 s(
      1). Highest oxidizing activity towards ABTS was obtained at 85 degrees C.
      However, after 1 h incubation of CotA at 70 degrees C and 80 degrees C, a
      residual activity of 43% and 8%, respectively, was measured. Furthermore,
      oxidation of several phenolic acids and one non-phenolic acid by CotA was
      investigated. CotA failed to oxidize coumaric acid, cinnamic acid, and vanillic
      acid, while syringic acid was oxidized to 2,6-dimethoxy-1,4-benzoquinone.
      Additionally, dimerization of sinapic acid, caffeic acid, and ferulic acid by
      CotA was observed, and highest activity of CotA was found towards sinapic acid.

PMID- 18330562
TI  - Glucose oxidase: natural occurrence, function, properties and industrial
      applications.
AB  - Glucose oxidase (GOX) from Aspergillus niger is a well-characterised glycoprotein
      consisting of two identical 80-kDa subunits with two FAD co-enzymes bound. Both
      the DNA sequence and protein structure at 1.9 A have been determined and reported
      previously. GOX catalyses the oxidation of D: -glucose (C(6)H(12)O(6)) to D: 
      gluconolactone (C(6)H(10)O(6)) and hydrogen peroxide. GOX is produced naturally
      in some fungi and insects where its catalytic product, hydrogen peroxide, acts as
      an anti-bacterial and anti-fungal agent. GOX is Generally Regarded As Safe, and
      GOX from A. niger is the basis of many industrial applications. GOX-catalysed
      reaction removes oxygen and generates hydrogen peroxide, a trait utilised in food
      preservation. GOX has also been used in baking, dry egg powder production, wine
      production, gluconic acid production, etc. Its electrochemical activity makes it
      an important component in glucose sensors and potentially in fuel cell
      applications. This paper will give a brief background on the natural occurrence,
      functions as well as the properties of glucose oxidase. A good coverage on the
      diverse uses of glucose oxidase in the industry is presented with a brief outline
      on the working principles in the various settings. Furthermore, food grade GOX
      preparations are relatively affordable and widely available; the readers may be
      encouraged to explore other potential uses of GOX. One example is that GOX
      catalysed reaction generates significant amount of heat (~200 kJ/mol), and this
      property has been mostly neglected in the various applications described so far.

PMID- 18330563
TI  - Virtual screening for novel quorum sensing inhibitors to eradicate biofilm
      formation of Pseudomonas aeruginosa.
AB  - The automated docking program DOCK 5.3.0 was applied to screening for quorum
      sensing inhibitors (QSIs) of Peudomonus aeruginosa from a database containing 51
      active components of Traditional Chinese Medicines with antibacterial activity.
      Five potential QSIs were revealed by the computer-based virtual screening. The
      compounds 3, 4, 5, 6, 7 inhibit biofilm formation of P. aeruginosa at a
      concentration of 200 microM. Compound 4 (baicalein) does not inhibit the growth
      of P. aeruginosa; however, it significantly inhibits biofilm formation of the
      bacteria at a lower concentration of 20 microM and promoted proteolysis of the
      signal receptor TraR protein in Escherichia coli at 4-40 mM. Baicalein and
      ampicillin showed synergistic activity against P. aeruginosa. These results
      suggested that baicalein can interfere with quorum sensing system of P.
      aeruginosa and will be developed as antibacterial agent with novel target.

PMID- 18330564
TI  - Monitoring of microbial adhesion and biofilm growth using electrochemical
      impedancemetry.
AB  - Electrochemical impedance spectroscopy was tested to monitor the cell attachment
      and the biofilm proliferation in order to identify characteristic events induced
      on the metal surface by Gram-negative (Pseudomonas aeruginosa PAO1) and Gram
      positive (Bacillus subtilis) bacteria strains. Electrochemical impedance spectra
      of AISI 304 electrodes during cell attachment and initial biofilm growth for both
      strains were obtained. It can be observed that the resistance increases gradually
      with the culture time and decreases with the biofilm detachment. So, the
      applicability of electric cell-substrate impedance sensing (ECIS) for studying
      the attachment and spreading of cells on a metal surface has been demonstrated.
      The biofilm formation was also characterized by the use of scanning electron
      microscopy and confocal laser scanning microscopy and COMSTAT image analysis. The
      electrochemical results roughly agree with the microscope image observations. The
      ECIS technique used in this study was used for continuous real-time monitoring of
      the initial bacterial adhesion and the biofilm growth. It provides a simple and
      non-expensive electrochemical method for in vitro assessment of the presence of
      biofilms on metal surfaces.

PMID- 18330565
TI  - Action of antimicrobial substances produced by different oil reservoir Bacillus
      strains against biofilm formation.
AB  - Microbial colonization of petroleum industry systems takes place through the
      formation of biofilms, and can result in biodeterioration of the metal surfaces.
      In a previous study, two oil reservoir Bacillus strains (Bacillus licheniformis
      T6-5 and Bacillus firmus H(2)O-1) were shown to produce antimicrobial substances
      (AMS) active against different Bacillus strains and a consortium of sulfate
      reducing bacteria (SRB) on solid medium. However, neither their ability to form
      biofilms nor the effect of the AMS on biofilm formation was adequately addressed.
      Therefore, here, we report that three Bacillus strains (Bacillus pumilus LF4 --
      used as an indicator strain, B. licheniformis T6-5, and B. firmus H(2)O-1), and
      an oil reservoir SRB consortium (T6lab) were grown as biofilms on glass surfaces.
      The AMS produced by strains T6-5 and H(2)O-1 prevented the formation of B.
      pumilus LF4 biofilm and also eliminated pre-established LF4 biofilm. In addition,
      the presence of AMS produced by H(2)O-1 reduced the viability and attachment of
      the SRB consortium biofilm by an order of magnitude. Our results suggest that the
      AMS produced by Bacillus strains T6-5 and H(2)O-1 may have a potential for
      pipeline-cleaning technologies to inhibit biofilm formation and consequently
      reduce biocorrosion.

PMID- 18330566
TI  - Overexpression of yeast S-adenosylmethionine synthetase metK in Streptomyces
      actuosus leads to increased production of nosiheptide.
AB  - S-Adenosylmethionine (SAM) is synthesized via the metabolic reaction involving
      adenosine triphosphate and L-methionine that is catalyzed by the enzyme S
      adenosyl-L-methionine synthetase (SAM-s) and encoded by the gene metK. In the
      present study, metK with the absence of introns from Saccharomyces cerevisiae was
      introduced into Streptomyces actuosus, a nosiheptide (Nsh) producer.
      Intracellular SAM levels were determined by high-pressure liquid chromatography.
      Through optimizing the nutrient content of the medium, it was shown that
      increased SAM production induced by the overexpression of SAM-s leads to an
      increase in the intracellular cysteine pool and overproduction of Nsh in S.
      actuosus. This investigation shows that increased SAM promotes the elevated
      production of the non-ribosomal thiopeptide Nsh in Streptomyces sp.

PMID- 18330567
TI  - Extraction of extracellular polymeric substances from extreme acidic microbial
      biofilms.
AB  - The efficiency of five extraction methods for extracellular polymeric substances
      (EPS) was compared on three benthic eukaryotic biofilms isolated from an extreme
      acidic river, Rio Tinto (SW, Spain). Three chemical methods (MilliQ water, NaCl,
      and ethylenediamine tetraacetic acid [EDTA]) and two physical methods (Dowex 50.8
      and Crown Ether cation exchange resins) were tested. The quality and quantity of
      the EPS extracted from acidic biofilms varied according to which EPS extraction
      protocol was used. Higher amounts were obtained when NaCl and Crown Ether resins
      were used as extractant agents, followed by EDTA, Dowex, and MilliQ. EPS amounts
      varied from approximately 155 to 478 mg g(-1) of dry weight depending on the
      extraction method and biofilm analyzed. EPS were primarily composed of
      carbohydrate, heavy metals, and humic acid, plus small quantities of proteins and
      DNA. Neutral hexose concentrations corresponded to more than 90% of the total EPS
      dry weight. The proportions of each metals in the EPS extracted with EDTA are
      similar to the proportions present in the water from each locality where the
      biofilms were collected except for Al, Cu, Zn, and Pb. In this study, the
      extracellular matrix heavy metal sorption efficiencies of five methods for
      extracting EPS from eukaryotic acidic biofilms were compared.

PMID- 18330568
TI  - NADH- vs NADPH-coupled reduction of 5-hydroxymethyl furfural (HMF) and its
      implications on product distribution in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae alcohol dehydrogenases responsible for NADH-, and NADPH
      specific reduction of the furaldehydes 5-hydroxymethyl-furfural (HMF) and
      furfural have previously been identified. In the present study, strains
      overexpressing the corresponding genes (mut-ADH1 and ADH6), together with a
      control strain, were compared in defined medium for anaerobic fermentation of
      glucose in the presence and absence of HMF. All strains showed a similar
      fermentation pattern in the absence of HMF. In the presence of HMF, the strain
      overexpressing ADH6 showed the highest HMF reduction rate and the highest
      specific ethanol productivity, followed by the strain overexpressing mut-ADH1.
      This correlated with in vitro HMF reduction capacity observed in the ADH6
      overexpressing strain. Acetate and glycerol yields per biomass increased
      considerably in the ADH6 strain. In the other two strains, only the overall
      acetate yield per biomass was affected. When compared in batch fermentation of
      spruce hydrolysate, strains overexpressing ADH6 and mut-ADH1 had five times
      higher HMF uptake rate than the control strain and improved specific ethanol
      productivity. Overall, our results demonstrate that (1) the cofactor usage in the
      HMF reduction affects the product distribution, and (2) increased HMF reduction
      activity results in increased specific ethanol productivity in defined mineral
      medium and in spruce hydrolysate.

PMID- 18330569
TI  - Clinical effects of transcatheter hepatic arterial embolization with holmium-166
      poly(L-lactic acid) microspheres in healthy pigs.
AB  - PURPOSE: The aim of this study is to evaluate the toxicity of holmium-166 poly(L
      lactic acid) microspheres administered into the hepatic artery in pigs. METHODS:
      Healthy pigs (20-30 kg) were injected into the hepatic artery with holmium-165
      loaded microspheres ((165)HoMS; n=5) or with holmium-166-loaded microspheres
      ((166)HoMS; n=13). The microspheres' biodistribution was assessed by single
      photon emission computed tomography and/or MRI. The animals were monitored
      clinically, biochemically, and ((166)HoMS group only) hematologically over a
      period of 1 month ((165)HoMS group) or over 1 or 2 months ((166)HoMS group).
      Finally, a pathological examination was undertaken. RESULTS: After microsphere
      administration, some animals exhibited a slightly diminished level of
      consciousness and a dip in appetite, both of which were transient. Four lethal
      adverse events occurred in the (166)HoMS group due either to incorrect
      administration or comorbidity: inadvertent delivery of microspheres into the
      gastric wall (n=2), preexisting gastric ulceration (n=1), and endocarditis (n=1).
      AST levels were transitorily elevated post-(166)HoMS administration. In the other
      blood parameters, no abnormalities were observed. Nuclear scans were acquired
      from all animals from the (166)HoMS group, and MRI scans were performed if
      available. In pigs from the (166)HoMS group, atrophy of one or more liver lobes
      was frequently observed. The actual radioactivity distribution was assessed
      through ex vivo (166m)Ho measurements. CONCLUSION: It can be concluded that the
      toxicity profile of HoMS is low. In pigs, hepatic arterial embolization with
      (166)HoMS in amounts corresponding with liver-absorbed doses of over 100 Gy, if
      correctly administered, is not associated with clinically relevant side effects.
      This result offers a good perspective for upcoming patient trials.

PMID- 18330570
TI  - Consolidation radioimmunotherapy of follicular lymphoma: a step towards cure?

PMID- 18330571
TI  - Surgical expertise and hip osteotomies.

PMID- 18330572
TI  - Immunological mechanisms in glaucoma.
AB  - Glaucoma is one of the most frequent causes of blindness worldwide. The elevated
      intraocular pressure does not explain glaucoma in all patients but can be
      considered as a risk factor of the disease. There are some evidences that
      autoimmune mechanisms may be involved in this disorder. This review attempts to
      demonstrate the findings about autoimmune mechanisms in glaucoma patients.
      Consistent up- and down-regulations in the autoantibody profiles against ocular
      antigens are present in glaucoma patients. These changes in natural autoimmunity
      could be found in independent study populations and might be a promising tool for
      glaucoma detection.

PMID- 18330573
TI  - [Odontogenic cysts].
AB  - Odontogenic cysts form a group of diseases whose origin is linked to the
      persistence of epithelium resulting from the complex embryonic development of the
      teeth and jaws within the connective tissue. Inflammatory reactions of the
      surrounding area of the persisting odontogenic epithelium accompany epithelium
      proliferation, which leads to the development of a gradually expanding cavity
      that supersedes the surrounding structure. The correlation between activity of
      the inflammatory reaction and the development of the epithelial proliferation
      results in a relatively broad variation of histological features of the cyst
      wall. Since classification of cyst forms depends on their topographical features,
      clinical information on the classification of variations is urgently needed. For
      the classification of their clinical course of development and, in particular, in
      order to differentiate them from cystic odontogenic tumors of the jaw region, a
      histological examination of cyst wall tissue is necessary, all the more so since
      the development of a carcinoma deriving from the odontogenic epithelium has only
      been described in very few cases.

PMID- 18330574
TI  - A newborn with chylous ascites caused by intestinal malrotation associated with
      heterotaxia syndrome.
AB  - Chylous ascites is a rare entity in infants. An uncommon cause of chylous ascites
      is intestinal malrotation. We report a case of a neonate with heterotaxia
      polysplenia syndrome and intestinal malrotation who presented with chylous
      ascites and subsequently developed duodenal obstruction from midgut volvulus. He
      was successfully treated with peritoneal drainage, surgical intervention, and
      nutritional support. A brief overview of the association of chylous ascites,
      intestinal rotational anomalies and heterotaxia syndromes is discussed.

PMID- 18330575
TI  - Thoracoscopic right middle lobar bronchus reimplantation for iatrogenic injury in
      infant: is it a good option?
AB  - We report the first case in the literature of thoracoscopic bronchial
      reimplantation in 5 month-old boy. The child was born with congenital cystic
      adenomatoid malformation of the right lower lobe associated with lower intralobar
      pulmonary sequestration diagnosed prenatally. An iatrogenic middle lobar bronchus
      injury was detected per-operatively during thoracoscopic lobectomy. Management
      and follow-up were exposed.

PMID- 18330576
TI  - Management of brachial artery aneurisms in infants.
AB  - Brachial artery aneurisms in children under 1 year of age are very rare. The main
      risk is distal ischaemic complication. We report four infants suffering from
      brachial artery aneurism of unknown origin. In all cases we used Doppler
      ultrasonography to validate the clinical diagnosis. Pre-operative vascular check
      up was negative for other aneurismal location. Surgical excision with direct end
      to-end anastomosis was possible in one patient; the others required interposition
      of an autologous venous graft. At discharge, patients were given oral aspirin for
      a few weeks. Histological examination revealed one pseudoaneurism and three true
      aneurisms. There were no complications either postoperatively or at 18 months
      follow-up. Arterial ligation might be indicated in only two situations: aneurism
      distal to profunda brachii artery, or chronic wall thrombus completely occluding
      (but distal perfusion through a neovascularization must be assessed first on
      angiography). Surgical excision with arterial reconstruction is the standard
      treatment. Endovascular treatment is not suitable because such a procedure in an
      infant would generate excessive radiation exposure, and a risk of stent migration
      with limb growth. In the case of an initial isolated and idiopathic presentation,
      or of false aneurism, clinical follow-up at 1 year is sufficient. In the case of
      secondary lesion, multiple initial presentation or relapse, life-long follow-up
      with repeated corporal imaging should be performed.

PMID- 18330577
TI  - Cavernous, arteriovenous, and mixed hemangioma-lymphangioma of the rectosigmoid:
      rare causes of rectal bleeding--case series and review of the literature.
AB  - INTRODUCTION: Cavernous hemangiomas of the sigmoid colon and rectum are uncommon
      vascular malformations usually found in young adults with a long history of
      episodic and painless rectal bleeding. Alternatively, they may present with
      massive life-threatening hemorrhage. DISCUSSION: We report three cases of
      hemangioma of the rectosigmoid including one case of cavernous hemangioma, one
      case of arteriovenous hemangioma, and one case of hemangiolymphangiomatosis with
      emphasis on clinical presentation, radiologic, operative, and pathologic
      findings. Definitive treatment consists of complete resection with a sphincter
      preserving procedure or abdominoperineal resection, based on extent of disease.
      CONCLUSION: Therapy is typically delayed by several years in these patients due
      to erroneous diagnosis and failed treatment of hemorrhoids and inflammatory bowel
      disease. Relative to hemangiomas, lymphangiomas of the rectosigmoid are even more
      rare and when symptomatic, present with rectal bleeding and pelvic pain.

PMID- 18330578
TI  - Prognostic factors in 1,138 Iranian colorectal cancer patients.
AB  - BACKGROUND AND AIM: The incidence of colorectal cancer is increased in Iran in
      recent years and colorectal cancer is the fourth most common cancer in both
      sexes. The aim of this study is to define the prognostic factors in Iranian
      colorectal cancer patients using univariate and multivariate methods. MATERIALS
      AND METHODS: All patients with colorectal cancer diagnosis according to the
      pathology report that registered in our cancer registry center in the period
      between Jan 2002 until Jan 2007 were eligible for this study. These patients were
      followed up by telephone contact. The probability curves for survival were
      calculated according to the Kaplan-Meier method and compared by the Log-rank
      test. Multivariate analysis was carried out using the Cox proportional hazard
      model. RESULTS: Of 1,138 cases, a survival information was available on 1,127
      patients, 690 males (61.2%) and 437 females (38.8%). Mean survival time was 105.1
      (CI: 95.1-115.1) months. The Kaplan-Meier method indicated that the 1, 3, 5, 7,
      10, and 15 years of survival rates are 91.1%, 73.1%, 61.0%, 54.9%, 47.9%, and
      25.9%, respectively. According to the univariate analysis, the factors
      influencing overall survival rate were the following: type of first treatment,
      body mass index, marital status, tumor grade, extent of wall penetration, distant
      metastasis, regional lymph nodes metastasis, and pathologic stage of tumor. The
      following five variables were independent prognostic factors for survival as
      determined by multivariate analysis: tumor size, metastasis of tumor, body mass
      index, marital status, and grade of tumor. CONCLUSION: Our results showed that
      stage of tumor, distant metastasis, grade of tumor, and tumor size should be
      considered as the most important prognostic factors in colorectal cancer
      patients.

PMID- 18330579
TI  - Discoid lupus erythematosus (DLE)-like lesions induced by capecitabine.

PMID- 18330580
TI  - Anti-p53 autoantibody in colorectal cancer: prognostic significance in long-term
      follow-up.
AB  - BACKGROUND: The prognostic significance of anti-53 autoantibody in colorectal
      cancer (CRC) patients is unclear due to measurement of overall rather than
      disease-specific survival and generally short follow-up periods in many studies.
      We aim to investigate prognostic significance of anti-p53 auto-antibodies in a
      study with long-term follow-up (minimum 5 years). METHODS: ELISA for anti-p53
      autoantibody was assayed in serum from 92 patients with CRC and 28 controls.
      RESULTS: Anti-p53 autoantibody was found in 20 patients (21.7%) and none of the
      controls. No difference in Dukes' (A/B vs. C/D), Stage (I/II vs. III/IV), T1/2
      vs. T3/4, N0 vs. N1/2, M0 vs. M1, poor vs. well/moderate differentiation and
      proximal vs. distal CRC was observed. Median overall survival was 62 months and
      median disease-specific survival was 73 months. Dukes' C/D, Stage III/IV, N1/2
      and M1 were associated with poor disease-specific survival in univariate
      analysis. Stage III/IV was an independent prognostic factor in overall and
      disease-free survival in multivariate analysis. Anti-p53 autoantibody sero
      positivity did not influence overall (p = 0.980) or disease-specific survival (p
      = 0.874). Median overall survival in anti-p53 autoantibody positive patients was
      62 months vs. 60 months in anti-53 autoantibody negative patients. Median disease
      specific survival in anti-p53 autoantibody positive patients was 73 months vs. 82
      months. CONCLUSION: Anti-p53 autoantibody is not related to clinical parameters
      of CRC and has no prognostic significance in long-term follow-up.

PMID- 18330581
TI  - Survival and symptomatic benefit from palliative primary tumor resection in
      patients with metastatic colorectal cancer: a review.
AB  - BACKGROUND AND AIMS: Patients with metastatic colorectal cancer have a limited
      life expectancy and are at risk for life-threatening tumor-related obstruction,
      perforation, and hemorrhage. Though surgical resection is performed frequently in
      this setting, its true benefit is not well-established. MATERIALS AND METHODS: We
      reviewed the medical literature from 1996-2006 using the search terms metastatic
      colorectal cancer and primary resection to find studies that evaluated the
      management of primary tumors in metastatic colorectal cancer. All search results
      were included in our analysis and were assessed on the basis of methodologic
      quality. RESULTS/FINDINGS: Twelve relevant studies were identified; ten were
      single-institution retrospective reviews and two were population-based studies
      using National Cancer Institute's Surveillance, Epidemiology, and End-Results
      database. No prospective or randomized studies were identified. Approximately 70%
      of patients diagnosed with metastatic colorectal cancer in the USA undergo
      primary tumor resection; only a minority have this done for tumor-related
      symptoms or as part of potentially curative resection. The postoperative
      mortality ranged from 9.0-11.2% in large cancer registries but was often lower in
      major cancer centers. Resection of asymptomatic primary tumors was frequently
      associated with prolonged survival but was not found to reduce significantly the
      incidence of life-threatening tumor-related complications.
      INTERPRETATION/CONCLUSION: Retrospective data suggest that non-curative resection
      of asymptomatic colorectal primary tumors may prolong survival; however,
      selection bias and unaccounted clinical factors may explain this observation.
      Prospective, randomized surgical trials are needed to test the role of primary
      tumor resection in this setting, especially because of its current widespread
      use, and its associated cost, morbidity, and high postoperative mortality.

PMID- 18330582
TI  - Diagnostic precision of endoanal MRI in the detection of anal sphincter
      pathology: a meta-analysis.
AB  - OBJECTIVE: This study aims to evaluate the diagnostic precision of endoanal
      magnetic resonance imaging in identifying anal sphincter injury and/or atrophy
      when compared with either endoanal ultrasound or surgical diagnosis. MATERIALS
      AND METHODS: Quantitative meta-analysis was performed on nine studies, comparing
      endoanal MRI with endoanal ultrasound or surgical diagnosis in 157 patients.
      Sensitivity, specificity, and diagnostic odds ratio were calculated for each
      study. Summary receiver operating characteristic curves (SROC) and subgroup
      analysis were undertaken. RESULTS: The overall sensitivity and specificity of
      endoanal MRI for external sphincter injury was 0.78 (95%CI: 0.66-0.84) and 0.66
      (95%CI: 0.51-0.79), respectively. For internal sphincter injury detection, this
      was 0.63 (95%CI: 0.50-0.74) and 0.71 (95%CI: 0.60-0.81), respectively. For
      detection of atrophy, this was 0.86 (95%CI: 0.71-0.95) and 0.82 (95%CI: 0.65
      0.93), respectively. The area under the SROC curve and diagnostic odds ratio were
      0.84 (SE = 0.07) and 6.14 (95%CI: 2.17-17.4) for external sphincter injury, 0.79
      (SE = 0.07) and 4.60 (95%CI: 1.75-12.15) for internal sphincter injury, and 0.92
      (SE = 0.08) and 21.49 (95%CI: 2.87-160.64) for sphincter atrophy. CONCLUSION:
      Endoanal MRI was sensitive and specific for the detection of external sphincter
      injury and especially sphincter atrophy. It may be useful as an alternative to
      endoanal ultrasound in patients presenting with fecal incontinence, although
      further clinical studies are needed to identify its best application in clinical
      practice.

PMID- 18330583
TI  - Lack of effect on bone healing of injectable BMP-2 augmented hyaluronic acid.
AB  - INTRODUCTION: Autologous bone graft is the gold standard for the filling of large
      osseous defects. Because of its limited supply and complications such as pain,
      bleeding or infection, the development of alternative bone substitutes has been
      the subject of several studies. In clinical practice, the most commonly used bone
      substitutes are calcium phosphates like hydroxyapatite or tricalcium phosphate.
      With the aim to improve the osseointegration of these materials, growth factors
      such as bone morphogenetic protein-2 (BMP-2) have been added. Preferably, an
      injectable bone substitute should be made available. Hyaluronic acid is a
      component of the extracellular matrix of many tissues, including bone. We
      examined the bone regenerative effect of commercially available, injectable
      hyaluronic acid (Hyalart) with and without addition of bone morphogenetic protein
      2 (BMP-2). MATERIALS AND METHODS: Trepanation defects of 9.4 mm diameter in the
      intercondylar groove of sheep femora were filled with pure and augmented (200
      microg BMP-2) hyaluronic acid. As controls, empty defects and defects treated
      with autologous bone graft harvested from the contralateral side were used. After
      3 months, the defects were analysed by fluorescence microscopy after intravital
      fluorescence staining, contact microradiography, histology and histomorphometry.
      RESULTS: Treatment of the defects with loaded and unloaded hyaluronic acid
      resulted in a significant lack of bone formation inside the defects. Untreated
      defects showed an amount of 5.1% newly formed bone, and defects treated with
      autologous bone graft revealed a bone content of 20%. The difference between both
      groups was statistically significant (P < 0.05). Furthermore, there was neither a
      remarkable effect in the periphery of the defects nor ectopic bone formation.
      CONCLUSION: The application of the used injectable hyaluronic acid (Hyalart) with
      and without BMP-2 is not advantageous as sole bone substitute for the filling of
      osseous defects.

PMID- 18330584
TI  - A case of co-existing pigmented villonodular synovitis and tuberculosis infection
      of the foot and ankle.
AB  - A woman presented with chronic left ankle pain and swelling with no systemic
      upset. Magnetic resonance imaging suggested pigmented villonodular synovitis
      (PVNS) of her left ankle joint and flexor hallucis longus tendon. Combined
      arthroscopic and open synovectomy was performed. Histological examination of the
      synovium confirmed the diagnosis of PVNS, but culture of the diseased synovium
      yielded mycobacterium tuberculosis. This case illustrates the possibility of
      double pathology and the importance in excluding tuberculosis infection.

PMID- 18330585
TI  - Ankle stiffness and osteoarthritis in fracture-dislocation: an avoidable
      complication or natural history.

PMID- 18330586
TI  - Association study of NFKB1 and SUMO4 polymorphisms in Chinese patients with
      psoriasis vulgaris.
AB  - Nuclear factor kappa-beta (NF-kappaB) is a critical transcription factor
      modulating the expression of many genes involved in the pathogenesis of
      psoriasis. SUMO4 is a negative regulator of NF-kappaB in the cell-signaling
      pathway. Two functional polymorphisms of the NFKB1 and SUMO4 genes have been
      found to be associated with the risks of some autoimmune-related diseases, but no
      published study has investigated the role of these polymorphisms in the etiology
      of psoriasis in the Chinese population. In this hospital-based, case-control
      study of 519 Chinese psoriasis vulgaris patients and 541 matched controls, we
      genotyped the NFKB1-94 ins/delATTG and the SUMO4 rs237025 A>G polymorphisms and
      assessed their respective associations with psoriasis vulgaris risk. We found
      that the genotype distribution of NFKB1-94 ins/delATTG polymorphism was
      statistically different between psoriasis patients and controls (P = 0.031). But
      the difference was not still statistically significant after correction for
      multiple comparisons. The frequency of wild WW genotype in psoriasis patients was
      statistically higher than that in controls (35.8 vs. 29.0%, respectively, P =
      0.021). The W allele frequency in cases was also significantly higher than that
      in controls (59.7 vs. 54.1%, P = 0.008). Compared with the DD genotype, a
      significantly increased psoriasis risk was associated with the NFKB1 WW genotype
      (adjusted OR = 1.57, 95% CI = 1.10-2.24). In addition, the WW genotype frequency
      was also statistically higher in the psoriatic subgroups of onset age <or=40,
      PASI >20, male patients and sporadic patients than that in controls. But, no
      associations of the SUMO4 rs237025 A>G polymorphism with the susceptibility of
      psoriasis were detected. In conclusion, we found a marginal association between
      the NFKB1-94 ins/delATTG WW genotype and the increased psoriasis vulgaris risk
      and the association was more evident in the subgroups of onset age <or=40, PASI
      >20, male patients and sporadic patients in Chinese.

PMID- 18330587
TI  - Acute stretch promotes endothelial cell proliferation in wounded healing mouse
      skin.
AB  - We have developed a novel in vivo model utilizing acute stretch to investigate
      endothelial cell proliferation as a marker of vascular growth in healing mouse
      skin. This study is a follow-up to ones revealing immediate stretch improves
      blood flow, decreases total tissue necrosis, and induces tissue insulin
      transcription. Dorsal distally based flaps of skin were stretched for 3 min using
      linear (skin hook) plus hemispherical load cycling (inflated subcutaneous
      silicone catheter). Unstretched, wounded skin along the back and sternum served
      as postoperative controls. Laser Doppler flowmetry demonstrated a threefold
      increase in flap perfusion at postoperative day 7. A stretch-induced sixfold
      increase in endothelial cell mitogenesis accompanied enhancements in blood flow
      and extracorporal wound healing over the sternum. Western blots revealed up
      regulation/activation of insulin and mitogenic signaling intermediates in
      stretched skin. Activated insulin and insulin growth factor receptors
      (pIR/pIGFR), protein kinase B (Akt, pAkt), vascular endothelial growth factor
      (VEGF) and vascular endothelial growth factor receptor 2 (flk-1) were among the
      identified stretch-responsive intermediates. These results indicate the benefits
      of acute stretch are mediated through enhanced vascularity as evidenced by
      endothelial cell mitogenesis and up-regulation/activation of insulin and key
      angiogenic effectors in dorsal distally based skin flaps.

PMID- 18330588
TI  - Anti-inflammatory effects of lithium gluconate on keratinocytes: a possible
      explanation for efficiency in seborrhoeic dermatitis.
AB  - Topical lithium (Li) gluconate has a beneficial effect on seborrhoeic dermatitis
      (SD), unlike oral lithium (Li) used in psychiatry. SD is an inflammatory
      dermatitis associated, in most of cases, with colonization by lipophilic yeasts
      of the genus Malassezia. However, the exact mechanism of action of Li gluconate
      in SD still remains unknown. The aim of our study was to investigate the effect
      of topical Li on cytokine secretion and innate immunity. For this purpose, we
      investigated first the modulatory effect of Li on two pro-inflammatory and two
      anti-inflammatory cytokine secretion and second, the modulatory effect of Li on
      Toll-like receptor (TLR) 2 and 4 expression by unstimulated and stimulated
      keratinocytes. Two different skin models were used: keratinocytes in monolayer
      and skin explants. In some of them, inflammation was induced with LPS (1 mug/ml)
      or zymosan (2 mg/ml). Then the skin models were incubated with Li gluconate
      (Labcatal*, Montrouge, France) at three different concentrations (1.6, 3, 5 mM)
      determined according to viability MTT test. Expression of TNFalpha, IL6, IL10,
      TGFbeta1, TLR2 and TLR4 was detected by immunohistochemistry (IHC). Cytokines
      were quantified by ELISA methods. Our results showed that the effect of Li on
      keratinocytes is dose-dependent. At low concentration (1.6 mM), Li enhanced
      TNFalpha secretion, whereas, at higher concentration (5 mM), Li significantly
      enhanced IL10 expression and secretion. However, there was no significant
      modulation of Li on IL6 and TGFbeta1 secretion. Moreover, Li at 5 mM
      significantly decreased TLR2 and TLR4 expressions by differentiated
      keratinocytes. As Li concentration during topical treatment is probably closer to
      5 mM than to 1 mM, the therapeutic effect of Li gluconate in DS may be explained
      by two anti-inflammatory actions: an increased expression and secretion of IL10
      and a decreased expression of TLR2 and TLR4 by keratinocytes. The diminution of
      TLR2 expression by Li may not allow MF to trigger inflammation response in
      lesional skin.

PMID- 18330589
TI  - How informed is consent in a modern ENT department.
AB  - The Department of Health issued a model consent form for use throughout the NHS
      from the 1st April 2002. Details of benefits and serious or frequent risks should
      be included on the form. We undertook a study to identify what proportion of
      complications from otolaryngology procedures were being recorded. Local morbidity
      and mortality records and case notes were examined from March to November 2004.
      Complications were identified and recorded. The consent forms for these
      operations were examined to identify if these complications had been recorded on
      the form prior to surgery. Complications were classified as "serious", causing
      significant morbidity or increasing length of hospital stay or "frequent",
      occurring in 1% or more of cases. A total of 2,978 operations were performed
      between March and November 2004. Seventy complications were identified in 60
      patients (2% of operated patients). Twenty-three complications were not recorded
      on the consent forms in 20 (33%) patients. A total of 67% of all the
      complications were documented on the form as potential problems resulting from
      planned operations. Seven (74%) of complications that occurred but were not
      recorded on the consent forms were judged as "serious" or "frequent". A
      significant proportion of serious or frequent complications are not being
      documented on the national consent forms before otolaryngological procedures and
      may not have been discussed. This may reflect a lack of openness during the
      consent process. In the current medical climate, this has serious ethical and
      medico-legal ramifications. It may also reflect a problem with the form and a
      need for a re-think of its design.

PMID- 18330590
TI  - Expression of adipokines in preimplantation rabbit and mice embryos.
AB  - Recent studies point to a role for adipokines in reproduction. Leptin is involved
      in embryo metabolism and may participate in embryo-maternal crosstalk. Little is
      known about potential roles of other adipokines in reproduction. We therefore
      studied the expression of adiponectin and pathway members during the pre- and
      periimplantation period in rabbits and mice. Adiponectin protein is localized in
      glandular epithelium of the rabbit endometrium on day 6 and 8 p.c. and in mouse
      endometrium on day 3.5 and 5 p.c. Rabbit, but not mice blastocysts express
      adiponectin mRNA. Adiponectin receptors one and two, adiponectin paralogues and
      PPARs were found in both species. Both, trophoblast and embryoblast were
      adiponectin positive. Real time PCR for adipoR1 and adipoR2 in rabbit blastocysts
      of different gastrulation stages at day 6 p.c. revealed a specific switch in
      expression: Expression was high in the trophoblast in early stages and in the
      embryoblast shortly prior to implantation. In conclusion, during the pre- and
      periimplantation period, members of the adiponectin pathway are expressed in
      endometrium and blastocysts, with a specific expression pattern in the embryonic
      disk of the gastrulating rabbit blastocyst, giving support to a role of the
      adipokine network in blastocyst differentiation and embryo-maternal interactions.

PMID- 18330591
TI  - Estrogen receptor subtypes localization shifts in cultured mouse ovarian
      follicles.
AB  - Estrogens play an important role in the growth, differentiation, and function of
      female reproductive tissues. Estrogen signals through estrogen receptors (ERs),
      members of the nuclear receptor superfamily. The two major forms, ERalpha and
      ERbeta, are expressed in the mouse ovary, where ERbeta is predominantly expressed
      in granulosa cells, and ERalpha in theca cells. In this study, we determined the
      expression pattern of ER subtypes within mouse follicles cultured from the early
      preantral stage up to the preovulatory stage and after an ovulatory stimulus in
      different culture conditions. Immunohistochemical studies performed at different
      time points of culture revealed that ERbeta was found exclusively in granulosa
      cell nuclei regardless of follicular growth stage or culture conditions. In
      contrast, ERalpha was found in oocyte, granulose, and theca cells, and its
      subcellular localization differed between follicular growth stages and culture
      conditions. A shift from a predominant cytoplasmic to a predominant nuclear
      immunolocalization was observed in granulosa cells as follicles reached the
      antral growth phase, and was postponed in culture conditions with minimal growth
      factor supplementation. In response to hCG, ERbeta protein levels in luteinized
      granulosa cells spectacularly declined to undetectable levels, while ERalpha
      immunostaining again shifted to cytoplasmic regions, but not in theca cells.

PMID- 18330592
TI  - Visually-evoked P300 and NOGO potentials as indicators of central nervous system
      function in patients with vibration syndrome.
AB  - OBJECTIVE: The present study aimed at clarifying the effects of vibration
      syndrome (VS) on recognition, memory, and selective attention as well as
      suppression of hand movement in the central nervous system (CNS). METHODS: Sixty
      four patients with VS due to previous exposure to vibration from chain-saw work
      (Ch) or rock drilling work (RD) and 53 age-matched controls were examined for
      visually evoked P300 (V-P300) and NOGO potentials (NOGO-P). The patient group was
      divided into two subgroups, one with VS due to Ch work (Ch group, N = 17) and the
      other with VS due to RD work (RD group, N = 44). RESULTS: ANOVA of latencies of V
      P300 between three groups including two subgroups by vibration tools and controls
      was significant (P < 0.001), with significant difference between the control and
      RD subgroup (P < 0.001) and between the Ch and RD subgroups (P < 0.001). ANOVA of
      V-P300 amplitude was also significant (P < 0.001), with significant difference
      between the control group and RD subgroup (P = 0.042). NOGO-P was recorded in 28
      of 37 controls (75.7%). Latencies of NOGO-P among VS patients were significantly
      delayed compared with those of controls (P = 0.0152). The proportions of subjects
      with abnormal values of V-P300 and NOGO-P among VS patients and RD operators were
      significantly higher than those in the control. CONCLUSION: These findings
      suggest that VS affects CNS function as represented by V-P300 and NOGO-P.

PMID- 18330593
TI  - Factors on working conditions and prolonged fatigue among physicians in Japan.
AB  - OBJECTIVE: Fatigue among physicians could affect patients' safety and physicians'
      health. Fatigue could be caused by unfavorable working conditions. However, there
      have been no studies on the working conditions and fatigue among physicians in
      Japan. The objective of this study was to determine the factors on working
      conditions associated with prolonged fatigue among physicians in Japan. METHODS:
      A questionnaire was mailed to physicians who graduated from one of the medical
      schools in Japan and who have had more than 3 years of experience in clinical
      practice. They were asked to assess 10 different aspects of their working
      conditions using a 5-point Likert scale. Prolonged fatigue was measured using the
      checklist of individual strength questionnaire. Multiple regression analysis was
      used to examine the multivariate relationship between the variables and prolonged
      fatigue. Data from 377 men and 101 women were analyzed in this study. RESULTS:
      For both male and female physicians, a harder workload was positively associated
      and better career satisfaction was negatively associated with prolonged fatigue.
      Prolonged fatigue was negatively associated with better relationships with other
      physicians and staff for male physicians and less personal time for female
      physicians. The adjusted variance in prolonged fatigue related to exposure
      variables was 26 and 29% in men and in women, respectively. CONCLUSIONS: The
      result of this study suggested that it is desirable to take these factors into
      consideration in the management of prolonged fatigue among physicians in Japan.

PMID- 18330594
TI  - The recurrent laryngeal nerve and the inferior thyroid artery--anatomical
      variations during surgery.
AB  - BACKGROUND AND AIMS: Recognition of variations of the inferior laryngeal nerve is
      essential. We aimed to investigate the relationship of the inferior laryngeal
      nerve with the inferior thyroid artery. MATERIALS AND METHODS: A study was
      undertaken between August 2005 and August 2006. A total of 253 adult patients
      undergoing thyroid surgery were included in this prospective, non-randomized
      study. Both sides of the thyroid gland were considered separately. RESULTS:
      Sixteen variations of the nerve were clarified. In the most observed variation,
      the nerve was deep to the artery. Two and three nervous branches were seen in
      22.5% and 1.6% of the patients, respectively. Bifurcation of the nerve was mostly
      observed on the left side. No non-recurrent laryngeal nerve was found.
      CONCLUSION: To avoid the risk of nerve damage during thyroid surgery, a good
      knowledge of the variations of the inferior laryngeal nerve is essential. This is
      important to achieve an undisturbed quality of life for the thyroid patient.

PMID- 18330595
TI  - Professor Dr. Dr. H.C. Christian H. Herfarth, Heidelberg.

PMID- 18330596
TI  - Social desirability in the measuring of patient satisfaction after treatment of
      coloproctologic disorders: on shortcomings of general bipolar satisfaction scales
      for quality management.
AB  - BACKGROUND AND AIMS: Within the field of medicine, much attention is being paid
      to quality management, whereby patient satisfaction plays a major role. In order
      to measure this construct, usually rather general, bipolar rating scales are
      applied. However, these scales are often susceptible to social desirability
      biases. PATIENTS-METHODS: Coloproctological patients were asked to complete a
      questionnaire with ratings of satisfaction and anxiety at two different points of
      measurement: One group while in treatment (N = 86) and a second group
      approximately 1 year after their treatment (N = 328). RESULTS: Even when
      controlling for relevant demographic influences, a clear decrease in intensity of
      the evaluation ratings is shown when the survey was administered 1 year after
      release from hospital as compared to during the patients' stay in hospital. For
      generally formulated scales of patient satisfaction, social desirability
      constitutes a significant bias. CONCLUSION: The usual conceptualization of a
      bipolar continuum of patient satisfaction or dissatisfaction must be renounced.
      Instead, questionnaires might be constructed in three steps which investigate
      problem dimensions at a medium level of concreteness. Only in this way can
      quality management gain credibility and trust within as well as beyond the field
      of medicine.

PMID- 18330597
TI  - Barley plasma membrane intrinsic proteins (PIP Aquaporins) as water and CO2
      transporters.
AB  - We identified barley aquaporins and demonstrated that one, HvPIP2;1, transports
      water and CO2. Regarding water homeostasis in plants, regulations of aquaporin
      expression were observed in many plants under several environmental stresses.
      Under salt stress, a number of plasma membrane-type aquaporins were down
      regulated, which can prevent continuous dehydration resulting in cell death. The
      leaves of transgenic rice plants that expressed the largest amount of HvPIP2;1
      showed a 40% increase in internal CO2 conductance compared with leaves of wild
      type rice plants. The rate of CO2 assimilation also increased in the transgenic
      plants. The goal of our plant aquaporin research is to determine the key
      aquaporin species responsible for water and CO2 transport, and to improve plant
      water relations, stress tolerance, CO2 uptake or assimilation, and plant
      productivity via molecular breeding of aquaporins.

PMID- 18330598
TI  - MHC class I immune evasion in MCMV infection.
AB  - Murine cytomegalovirus (MCMV) is a well-studied model of natural beta-herpesvirus
      infection. However, many questions remain regarding its control by and evasion of
      the immune response it generates. CD8 and CD4 T cells have both unique and
      redundant roles in control of the virus that differ based on the immunocompetence
      of the infected mice. MCMV encodes major histocompatibility complex (MHC) class I
      immune evasion genes that can have an impact in vitro, but their role in
      infection of immunocompetent mice has been difficult to identify. This review
      addresses the evidence for their in vivo function and suggests why they may be
      evolutionarily conserved.

PMID- 18330599
TI  - New tools to study the role of B cells in cytomegalovirus infections.
AB  - B cells were previously shown to mediate partial protection against CMV
      infection, as in the absence of B cells, latently infected mice were more
      susceptible to virus reactivation. It remains unclear if this effect stems from
      the loss of B cells as antibody producers or as antigen presenting cells. To
      address this fundamental question, we propose to make use of new mouse models
      that allow conditional ablation of B cells or that allow for the generation of
      mice with B cells that are not able to produce antibodies.

PMID- 18330600
TI  - The mechanism and kinetics of decomposition of 5-aminotetrazole.
AB  - The pathway and ab initio direct kinetics of the decomposition 5-aminotetrazole
      (5-ATZ) to HN(3) and NH(2)CN was investigated. Reactant, products and transition
      state were optimized with MP2 and B3LYP methods using 6-311G** and aug-cc-pVDZ
      basis sets. The intrinsic reaction coordinate curve of the reaction was
      calculated using the MP2 method with 6-311G** basis set. The energies were
      refined using CCSD(T)/6-311G**. Rate constants were evaluated by conventional
      transition-state theory (CVT) and canonical variational transition-state theory
      (TST), with tunneling effect over 300 to 2,500 K. The results indicated that the
      tunneling effect and the variational effect are small for the calculated rate
      constants. The fitted three-parameter expression calculated using the CVT and TST
      methods are k(T) = 4.07 x 10(11) x T(0.84) x e((-2.42 x 10(4))/T)s(-1) and k(T) =
      2.09 x 10(11) x T(0.89) x e((-2.36 x 10(4))/T)s(-1), respectively.

PMID- 18330601
TI  - Ab initio multireference study of Hetero-Diels-Alder reaction of buta-1,3-diene
      with alkyl glyoxylates.
AB  - Hetero-Diels-Alder (HDA) reaction of methyl glyoxylate with buta-1,3-diene has
      been investigated using multireference methods (complete active space SCF and
      multi-reference perturbation theory) and compared with several single-reference
      methods (including DFT) often used in calculations of catalysed [4+2]
      cycloadditions. Concerted and stepwise mechanisms, found in the literature, are
      compared. It is shown, that the stepwise mechanism may be a result of choosing
      unbalanced active space. Such choice leads to very close singlet and triplet
      states in the intermediate geometry - an artificial effect, that disappears if
      properly balanced active space is used (here, we use active space of 12 orbitals
      and 12 electrons). Conclusions concerning the mechanism and usefulness of the
      applied methodology are drawn, which might be important for theoretical
      investigation of stereoselectivity and specificity of catalysts for the HDA
      reaction.

PMID- 18330602
TI  - SHEF: a vHTS geometrical filter using coefficients of spherical harmonic
      molecular surfaces.
AB  - SHEF (spherical harmonic coefficient filter), a geometrical matching procedure
      constituting a preliminary step in the virtual high throughput screening of large
      databases of small drug-like molecules, is demonstrated. This filter uses a
      description of both the binding site of the target and the ligand surfaces using
      spherical harmonic polynomial expansions. Using this representation, which is
      based on limited sets of spherical harmonic coefficients, considerably reduces
      the complexity of surface complementarity calculation. As a first test, 188 known
      protein-ligand complexes were used, and the results of docking the abstracted
      ligands into the bare proteins using SHEF were compared to the original X-ray
      structures. The ability of SHEF to retrieve known ligands "hidden" in a virtual
      library of 1,000 randomly selected drug-like compounds is also demonstrated.

PMID- 18330603
TI  - Effect of microsolvation on zwitterionic glycine: an ab initio and density
      functional theory study.
AB  - The effect of microsolvation on zwitterionic glycine, considering both (-NH3(+))
      as proton donor and (-COO(-)) as proton acceptor at correlated ab initio (MP2)
      level and density functional methods (B3LYP, PW91, MPW1PW91 and PBE) using 6
      311++G** basis set has been reported. DFT methods have been employed so as to
      compare the performance/quality of different gradient-corrected correlation
      functionals (PW91, PBE), hybrid functionals (B3LYP, MPW1PW91) and to predict the
      near quantitative structural and vibrational properties, at reduced computational
      cost. B3LYP method outperforms among the different DFT methods for the computed
      hydrogen bond distances and found closer to the value obtained by correlated MP2
      level, whereas MPW1PW91 and PBE methods shows very similar values but
      approximately 0.03 A less, compared to B3LYP method. MP2 calculation and single
      point CCSD(T)//MP2 calculation have been considered to decompose the interaction
      energy, including corrections for basis set superposition error (BSSE). Moreover,
      charge distribution analysis has also been carried out to understand the long
      raised questions, how and why the two body energies have significant contribution
      to the total binding energy.

PMID- 18330604
TI  - Lemierre's syndrome and other disseminated Fusobacterium necrophorum infections
      in Denmark: a prospective epidemiological and clinical survey.
AB  - In a 3-year prospective study, all cases of disseminated Fusobacterium
      necrophorum infections found in Denmark from 1998 to 2001 were analysed, with the
      aim of describing the epidemiology and clinical features of the variants of
      Lemierre's syndrome and disseminated non-head-and-neck-associated F. necrophorum
      infections. Fifty-eight cases of Lemierre's syndrome were reported in previously
      healthy persons, with an incidence of 14.4 cases per million per year in
      youngsters aged 15-24 years old. There was no increase during the study period.
      Lemierre's syndrome originating from an oropharyngeal infection was seen in 37
      youngsters. An otogenic variant of Lemierre's syndrome was seen in 5 children
      with dissemination to nearby regions, and other variants of Lemierre's syndrome,
      e.g. from the sinuses and teeth, were seen in 16 adults. Patients often had
      metastatic infections already on admission and needed prolonged hospitalisation.
      The overall mortality of Lemierre's syndrome was 9%. Forty-two elderly patients
      had disseminated F. necrophorum infections originating from foci in lower parts
      of the body. They frequently had predisposing diseases, e.g. abdominal or
      urogenital cancers, which contributed to the high mortality of 26%. This study
      shows that the incidence of Lemierre's syndrome is higher than that previously
      found and has a characteristic age distribution. Early suspicion of the
      diagnosis, several weeks of antibiotic therapy, often combined with surgical
      drainage, is mandatory to lower the mortality. In disseminated non-head-and-neck
      associated F. necrophorum infections, underlying cancers must be considered.

PMID- 18330605
TI  - Potential of Eichhornia crassipes for biomass refining.
AB  - Here we explore the utilization of Eichhornia crassipes, commonly known as water
      hyacinth, as a competitive source of biomass for conversion to fuel.
      Ecologically, E. crassipes is the most undesirable of a class of noxious and
      invasive aquatic vegetation. Water hyacinth grows rapidly on the surface of
      waterways, forming a dense mat which depletes the surrounding environment of
      essential nutrients. These properties, rarely encountered in other plant systems,
      are features of an ideal feedstock for renewable biomass. The high characteristic
      water content limits the range over which the material can be transported;
      however it also makes E. crassipes a natural substrate for rapid microbial
      metabolism that can be employed as a potentially effective biological
      pretreatment technology. We show through a life cycle analysis that water
      hyacinth is a competitive feedstock with the potential to be produced at a cost
      of approximately 40 dollars per ton of dry mass.

PMID- 18330606
TI  - Regional variations of vertebral trabecular bone microstructure with age and
      gender.
AB  - The vertebral trabecular bone has a complex three-dimensional (3D)
      microstructure, with inhomogeneous morphology. A thorough understanding of
      regional variations in the microstructural properties is crucial for evaluating
      age- and gender-related bone loss of the vertebra, and may help us to gain more
      insight into the mechanism of the occurrence of vertebral osteoporosis and the
      related fracture risks. INTRODUCTION: The aim of this study was to identify
      regional differences in 3D microstructure of vertebral trabecular bone with age
      and gender, using micro-computed tomography (micro-CT) and scanning electron
      microscopy (SEM). METHODS: We used 56 fourth lumbar vertebral bodies from 28
      women and men (57-98 years of age) cadaver donors. The subjects were chosen to
      give an even age and gender distribution. Both women and men were divided into
      three age groups, 62-, 77- and 92-year-old groups. Five cubic specimens were
      prepared from anterosuperior, anteroinferior, central, posterosuperior and
      posteroinferior regions at sagittal section. Bone specimens were examined by
      using micro-CT and SEM. RESULTS: Reduced bone volume (BV/TV), trabecular number
      (Tb.N) and connectivity density (Conn.D), and increased structure model index
      (SMI) were found between ages 62 and 77 years, and between ages 77 and 92 years.
      As compared with women, men had higher Tb.N in the 77-year-old group and higher
      Conn.D in the 62- and 77-year-old groups. The central and anterosuperior regions
      had lower BV/TV and Conn.D than their corresponding posteroinferior region.
      Increased resorbing surfaces, perforated or disconnected trabeculae and
      microcallus formations were found with age. CONCLUSION: Vertebral trabeculae are
      microstructurally heterogeneous. Decreases in BV/TV and Conn.D with age are
      similar in women and men. Significant differences between women and men are
      observed at some microstructural parameters. Age-related vertebral trabecular
      bone loss may be caused by increased activity of resorption. These findings
      illustrate potential mechanisms underlying vertebral fractures.

PMID- 18330607
TI  - Severity of depression risk predicts health outcomes and recovery following
      surgery for hip-fractured elders.
AB  - This study examined how depression risk interfaces with health outcomes of hip
      fractured patients during the first year after hospital discharge. Physical
      function recovery and health outcome trajectories were much poorer for hip
      fractured elders with persistent depression risk than for those with transitory
      and no risk for depression. INTRODUCTION: This study examined how depression risk
      interfaces with the trajectories of physical activities and health-related
      quality of life (HRQoL) among hip-fractured elderly patients during the first 12
      months after hospital discharge. METHODS: Based on 12-month scores for the
      Chinese version of Geriatric Depression Scale, patients over age 60 years (N =
      147) were classified as (a) at persistent risk for depression, (b) at transitory
      risk for depression, and (c) at no risk for depression. Outcomes were measured by
      the Chinese Barthel Index and Medical Outcomes Study Short Form, Taiwan version,
      and analyzed by the generalized estimating equations approach. RESULTS: Patients
      who were at persistent risk for depression (n = 46, 31.3%) had much less chance
      of recovering activities of daily living (OR = 0.16, CI = 0.06-0.42) and walking
      ability (OR = 0.09, CI = 0.04-0.21) than patients at no risk for depression (n =
      36, 24.5%). The trajectories of SF-36 scores for the physical and mental health
      summary scales were significantly different among the three depression groups;
      those "at persistent risk for depression" were the poorest and those "at no risk
      for depression" were the best. CONCLUSION: These results may provide a reference
      for developing timely assessments and interventions for hip-fractured elders at
      risk of depression.

PMID- 18330608
TI  - Delayed spinal infection after laminectomy in a patient with rheumatoid arthritis
      interruptedly exposed to anti-tumor necrosis factor alpha agents.
AB  - We report a case of spondylodiscitis caused by Staphylococcus aureus 8 months
      after laminectomy of the lumbar spine, occurring in a rheumatoid arthritis (RA)
      patient interruptedly treated with anti-tumor necrosis alpha (TNFalpha) agents.
      The patient had suffered from seropositive RA for 2 years. An intravenous
      infusion (200 mg) of infliximab, a chimeric antibody against human TNFalpha, was
      introduced; however, due to Pneumocystis jiroveci pneumonia, this therapy was
      withdrawn. Four months later, the patient underwent an L3-L4 and L4-L5
      laminectomy for spinal stenosis. Two months after surgery, we started treatment
      with 25 mg of etanercept, a soluble humanized TNF receptor dimer, subcutaneously
      twice a week. At that time, wound healing was satisfactory and no evidence of
      infection was obtained. Eight months after surgery, septic spondylodiscitis of
      the lumbar spine occurred. To the best of our knowledge, this is the first case
      in the literature to show a delayed type of postoperative infection as a
      complication of non-instrumented orthopedic surgical procedures. Despite
      interruption of anti-TNFalpha therapy before surgery, patients may remain at risk
      of developing postoperative infections.

PMID- 18330609
TI  - Efficacy of intravenous alendronate for the treatment of glucocorticoid-induced
      osteoporosis in children with autoimmune diseases.
AB  - Our objective was to investigate the efficacy of intravenous alendronate for the
      treatment of glucocorticoid-induced osteoporosis (GIOP) in children with
      autoimmune diseases. Five children with autoimmune disease and GIOP were treated
      with 5 mg intravenous alendronate once every 3 months. After 1 and 2 years, we
      evaluated the changes in the Z score of the femoral neck bone mineral density
      (BMD), serum bone alkaline phosphatase, and urinary deoxypyridinoline. Six
      patients with GIOP, whose BMD could be observed over a 1-year period without
      alendronate treatment, were defined as controls. After 1 and 2 years of
      treatment, intravenous treatment significantly inhibited bone loss. The efficacy
      of alendronate demonstrated a significant correlation with a high level of bone
      turnover markers before alendronate treatment. Intravenous alendronate is
      considered to be a good choice for the treatment of GIOP because of its excellent
      efficacy. In addition, our study suggests that the efficacy of alendronate
      depends on the bone turnover of patients before treatment. Intervention with
      bisphosphonates during periods of high bone turnover may be recommended.

PMID- 18330610
TI  - Synovial cyst in juvenile idiopathic arthritis.
AB  - Small synovial cysts are a common manifestation of juvenile idiopathic arthritis;
      large brachial cysts, however, are a rare sign of the disease and they must be
      differentiated from other soft tissue swelling which are not related to articular
      involvement. We describe the case of three children with juvenile idiopathic
      arthritis who came to our attention with large synovial cysts. Ultrasonographic
      examination and MRI were performed in all cases, showing the real nature of the
      swelling and the connection to the joint. In all cases, swelling reduced and then
      disappeared with control of disease activity; in two cases, they reappeared in
      coincidence with a severe relapse of juvenile idiopathic arthritis. Brachial
      swellings represent a diagnostic challenge because they can be the clinical
      expression of a variety of diseases. In children with juvenile idiopathic
      arthritis who present with a sudden swelling of the upper arm, synovial cysts
      must be considered in the diagnostic workout, because they are a possible rare
      manifestation of juvenile idiopathic arthritis.

PMID- 18330612
TI  - Abstracts of the Four Provinces/JOGS Annual Scientific Meeting. November 23,
      2007. Dublin, Ireland.

PMID- 18330611
TI  - Efficacy of etanercept in the treatment of a patient with Behcet's disease.
AB  - Behcet's disease is a systemic inflammatory disorder without a specific treatment
      that is chosen on the basis of the type and severity of manifestation in the
      organ involved. More recently, biological agents like etanercept have emerged as
      possible therapeutic alternatives in patients resistant to conventional therapy.
      We describe the successful treatment for 1 year of resistant Behcet's disease
      with etanercept. After the administration of this drug, a resolution of the
      clinical, laboratory and instrumental picture was achieved with a suspension of
      immunosuppressive treatments and a reduction of steroid dependency (5 mg/day). No
      side effects were observed.

PMID- 18330613
TI  - Abstracts of the Irish Society for Rheumatology (ISR) and Irish Rheumatology
      Health Professionals Society (IRHPS) combined AGM. October 4-5, 2007. Galway,
      Ireland.

PMID- 18330614
TI  - Contrasting the seasonal variability of halogenated natural products and
      anthropogenic hexachlorocyclohexanes in the southern Norwegian atmosphere.
AB  - Halogenated natural products (HNPs) are increasingly recognized as compounds of
      marine environmental samples. In this study, we explored whether the annual
      course of the concentrations of HNPs in ambient air samples was different from
      those of anthropogenic pollutants. For this purpose, air samples taken weekly at
      Lista, southern Norway, were analyzed by gas chromatography-mass spectrometry for
      anthropogenic aaeeee- (alpha-HCH) and aaaeee-hexachlorocyclohexane (gamma-HCH,
      lindane) isomers, as well as the HNPs 2,3,3',4,4',5,5'-heptachloro-1'-methyl-1,2'
      bipyrrole (Q1), 2,4-di- and 2,4,6-tribromoanisole (24-DBA, 246-TBA), and 2,4,6
      tribromophenol (246-TBP). Concentrations of HCH isomers were higher in the warmer
      summer months than in winter. By contrast, Q1, 24-DBA, 246-TBA, and 246-TBP
      showed much higher concentrations at the end of the year. Correlations between
      the concentrations of the compounds and air mass trajectories as well as further
      meteorological data are discussed. An unknown mixed halogenated substance was
      detected at high abundance during the summer months. High-resolution mass
      spectrometry and tandem mass spectrometric techniques were used to unravel the
      molecular structure, which was found to be C(7)H(8)Br(3)Cl, an elemental
      composition never reported before in the scientific literature.

PMID- 18330615
TI  - A giant atrial thrombosis in a patient with fontan circulation.
AB  - We described a case of a quasi obstructive thrombus in the right atrium in a
      patient with a Fontan palliation. Different medical imaging techniques helped us
      for diagnosis and management strategy. We discussed the therapeutic choice
      between thrombolysis or surgery.

PMID- 18330616
TI  - MR imaging in the triage of pregnant patients with acute abdominal and pelvic
      pain.
AB  - PURPOSE: To retrospectively assess the performance of MR imaging in the
      evaluation and triage of pregnant patients presenting with acute abdominal or
      pelvic pain. METHOD AND MATERIALS: MRI studies of pregnant patients who were
      referred for acute abdominal pain between 2001 and 2007 were included. MR images
      were retrospectively reviewed and compared with surgical and pathologic findings
      and clinical follow-up data. Analysis of imaging findings included evaluation of
      the visceral organs, bowel and mesentery, appendix (for presence of
      appendicitis), ovaries (detection and adnexal masses were evaluated), focal
      inflammation, presence of abscesses, and any other abnormal findings. RESULTS: A
      total of 118 pregnant patients were included. MR findings were inconclusive in 2
      patients and were positive for acute appendicitis in 11 patients (n = 9 confirmed
      by surgery, n = 2 improved without surgery). One patient with inconclusive MR had
      surgically confirmed appendicitis; the other patient with inconclusive MR had
      surgically confirmed adnexal torsion. Other surgical/interventional diagnoses
      suggested by MR imaging were adnexal torsion (n = 4), abscess (n = 4), acute
      cholecystitis (n = 1), and gastric volvulus (n = 1). Two patients with MR
      diagnosis of torsion improved without surgery. One patient with MR diagnosis of
      abscess had biliary cystadenoma at surgery. The rest of the MR diagnoses above
      were confirmed surgically or interventionally. MR imaging was normal in 67
      patients and demonstrated medically treatable etiology in 28 patients: adnexal
      lesions (n = 9), urinary pathology (n = 6), cholelithiasis (n = 4), degenerating
      fibroid (n = 3), DVT (n = 2), hernia (n = 1), colitis (n = 1), thick terminal
      ileum (n = 1), rectus hematoma (n = 1). Three of these patients had negative
      surgical exploration and one had adnexal mass excision during pregnancy. Other
      patients were discharged with medical treatment. The sensitivity, specificity,
      accuracy, positive predictive values (ppv), and negative predictive values (npv)
      of MR imaging for acute appendicitis, and surgical/ interventional diagnoses were
      90.0% vs. 88.9%, 98.1% vs. 95.0%, 97.5% vs. 94.1%, 81.8% vs. 76.2%, 99.1% vs.
      97.9%, respectively. CONCLUSION: MR imaging is an excellent modality for
      diagnosis of acute appendicitis and exclusion of diseases requiring
      surgical/interventional treatment. Therefore MR imaging is useful for triage of
      pregnant patients with acute abdominal and pelvic pain.

PMID- 18330617
TI  - Nodular fasciitis of the face: aesthetic considerations.
AB  - Nodular fasciitis is an uncommon tumor-like fibroblastic proliferation that
      occurs rarely in the head and neck region. A new case of nodular fasciitis
      occurring in the cheek of a 56-year-old woman is reported. The case was
      characterized by dental trauma preceding the appearance of the lesion (extraction
      of tooth 35). Histologically, the lesion consisted of proliferating fibroblasts
      and myofibroblasts presenting clinically as a rapidly growing subcutaneous
      nodule. A conservative surgical excision with curettage is the treatment of
      choice, and the lesion usually does not exhibit a tendency to recur. The clinical
      relevance of this condition relies on the fact that both the disorder and its
      surgical treatment may cause tissue distortion resulting in aesthetic compromise.
      Furthermore, it needs to be differentiated from malignancy due to its very rapid
      growth, its rich cellularity, and its high mitotic activity. Both of these
      aspects, i.e. aesthetic implications and differential diagnosis, have been
      discussed.

PMID- 18330618
TI  - Biplanar temple lift for lateral brow ptosis: comparison with uniplanar
      dissection technique.
AB  - BACKGROUND: The amount of lift achievable in the temple region has been limited
      by traditional uniplanar dissection techniques. A biplanar temple-lifting
      technique (BTL), involving a biplanar dissection both deep and superficial to the
      superficial musculoaponeurotic system (SMAS) of the temporal region, is
      described. This study compares the amount of temporal lifting that can be
      achieved using a uniplanar dissection with that achieved using a biplanar
      dissection. METHODS: Thirty-seven patients underwent bilateral temple lifting.
      Deep dissection was performed on the surface of the deep temporalis fascia. The
      skin flap was pulled in a superolateral direction and the skin overlap at the
      wound edge was measured. A SMAS flap was then dissected beneath the dermis from
      the anterior wound edge to the temporal hairline. The SMAS flap was suspended
      superolaterally and fixated to the deep temporalis fascia. The skin flap was
      again pulled in a superolateral direction and the amount of skin overlap was
      measured and compared. RESULTS: The average potential temple skin that could be
      excised using the traditional dissection technique was 15.1 mm (range, 7-24 mm).
      The average temple skin that was excised using the biplanar dissection technique
      was 21.8 mm (range, 14-30 mm). The biplanar technique was shown to offer, on
      average, a 48% increase in lift relative to the skin-only approach. There were no
      cases of wound dehiscence, necrosis, or overcorrection. CONCLUSION: Using the BTL
      technique to create a temporal SMAS flap, dissected free from overlying dermis as
      well as from deep temporal fascia, provides a more secure suspension of the
      temporal flap and significantly greater temple lift than a uniplanar dissection.
      The deep layering absorbs the tension of the lift, allowing for tensionless skin
      closure, thus decreasing the potential for scarring, hair loss, and necrosis. The
      increased mobility and higher suspension of the temporal flap allows for more
      skin excision and therefore a more pleasing lateral brow height.

PMID- 18330619
TI  - The impact of scientific information on ecosystem management: making sense of the
      contextual gap between information providers and decision makers.
AB  - Scientific information is not always effectively incorporated into decision
      making processes. This phenomenon seems to hold even when the information is
      aligned with an articulated need, is generated according to sound scientific
      procedures, and is packaged with end-user preferences in mind. We propose that
      contextual or cultural differences contribute significantly to the misalignment
      in communication between those who generate information and those who seek
      information for improved management of natural resources. The solution is to
      cultivate shared understanding, which in turn relies on acknowledgment and
      sharing of diverse values and attitudes. This constitutes a difficult challenge
      in a culturally diverse environment. Whereas cultural diversity represents wealth
      in experiences, knowledge and perspectives it can constrain the potential to
      develop the shared understandings necessary for effective integration of new
      information. This article illustrates how a lack of shared understanding among
      participants engaged in a resource-management process can produce and perpetuate
      divergent views of the world, to the extent that information and knowledge flows
      are ineffective and scientific information, even when requested, cannot be used
      effectively. Four themes were distilled from interviews with management and
      scientific staff of a natural resource-management agency in South Africa. The
      themes are used to illustrate how divergent views embedded in different cultures
      can discourage alignment of effort toward a common purpose. The article then
      presents a sense-making framework to illustrate the potential for developing
      shared understandings in a culturally diverse world.

PMID- 18330620
TI  - A model for predicting daily peak visitation and implications for recreation
      management and water quality: evidence from two rivers in Puerto Rico.
AB  - Visitor use surveys and water quality data indicates that high visitor use levels
      of two rivers in Puerto Rico does not appear to adversely affect several water
      quality parameters. Optimum visitor use to maximize visitor defined satisfaction
      is a more constraining limit on visitor use than water quality. Our multiple
      regression analysis suggests that visitor use of about 150 visitors per day
      yields the highest level of visitor reported satisfaction, a level that does not
      appear to affect turbidity of the river. This high level of visitor use may be
      related to the gregarious nature of Puerto Ricans and their tolerance for
      crowding on this densely populated island. The daily peak visitation model
      indicates that regulating the number of parking spaces may be the most effective
      way to keep visitor use within the social carrying capacity.

PMID- 18330621
TI  - Laparoscopic adrenalectomy for metachronous metastasis from renal cell carcinoma.
AB  - BACKGROUND: Metachronous adrenal metastases (AM) from renal cell carcinoma (RCC)
      are rare. We report our experience of surgical resection in this setting, with
      particular respect to laparoscopic approach and long-term outcome. METHODS: A
      retrospective review of 11 patients who underwent adrenalectomy for metachronous
      AM from RCC was conducted between 2002 and 2005 in a tertiary referral center.
      RESULTS: CT scan findings were those of an adrenal mass ranging from 2 to 13 cm
      in diameter with a basal density of 12 to 28 Hounsfield Units and strong
      heterogeneous enhancement following contrast injection. The surgical procedure
      consisted of controlateral (n = 5), ipsilateral (n = 2), and bilateral (n = 1)
      laparoscopic adrenalectomy, whereas three patients underwent controlateral open
      adrenalectomy for adrenal mass >10 cm. Nine patients were recurrence-free with a
      median follow-up of 34 months. In the remaining two patients, lung metastases
      were discovered at postoperative months 28 and 11, respectively. The former
      patient is alive and free of disease recurrence 32 months after lung metastasis
      resection, whereas the latter is currently being treated with sunitinib.
      CONCLUSIONS: This study confirms that prolonged overall and disease free-survival
      can be achieved in selected patient after laparosocpic adrenalectomy for AM from
      RCC.

PMID- 18330622
TI  - IATSIC symposium introduction.

PMID- 18330623
TI  - Incidence and risk factors of recurrence after surgery for pathology-proven
      diverticular disease.
AB  - BACKGROUND: Diverticular disease is a common problem in Western countries.
      Rationale for elective surgery is to prevent recurrent complicated diverticulitis
      and to reduce emergency procedures. Recurrent diverticulitis occurs in about 10%
      after resection. The pathogenesis for recurrence is not completely understood. We
      studied the incidence and risk factors for recurrence and the overall morbidity
      and mortality of surgical therapy for diverticular disease. METHODS: Medical
      records of 183 consecutive patients with pathology-proven diverticulitis were
      eligible for evaluation. Mean duration of follow-up was 7.2 years. Number of
      preoperative episodes, emergency or elective surgeries, type of operation, level
      of anastomosis, postoperative complications, persistent postoperative pain,
      complications associated with colostomy reversal, and recurrent diverticulitis
      were noted. The Kaplan-Meier method was used to calculate the cumulative
      probability of recurrence. Cox regression was used to identify possible risk
      factors for recurrence. RESULTS: The incidence of recurrence was 8.7%, with an
      estimated risk of recurrence over a 15-year period of 16%. Risk factors
      associated with recurrence were (younger) age (p < 0.02) and the persistence of
      postoperative pain (p < 0.005). Persistent abdominal pain after surgery was
      present in 22%. Eighty percent of patients who needed emergency surgery for acute
      diverticulitis had no manifestation of diverticular disease prior to surgery. In
      addition, recurrent diverticulitis was not associated with a higher percentage of
      emergency procedures. CONCLUSION: Estimated risk of recurrence is high and
      abdominal complaints after surgical therapy for diverticulitis are frequent.
      Younger age and persistence of postoperative symptoms predict recurrent
      diverticulitis after resection. The clinical implication of these findings needs
      further investigation. The results of this study support the careful selection of
      patients for surgery for diverticulitis.

PMID- 18330624
TI  - Attitudes of medical students toward careers in general surgery.
AB  - BACKGROUND: Changes to general surgical undergraduate curricula, alongside
      changes in work force and postgraduate training, may be associated with a decline
      in interest in surgical careers. This study examines the attitudes of students
      toward surgical training and their career intentions. METHODS: A prospective,
      questionnaire-based survey was submitted to final year students at the end of
      their general surgery attachment over a single academic year at a UK medical
      school. Career ambitions and reasoning were assessed. RESULTS: Of 223 eligible
      students, 193 (87%) completed the questionnaire. There were 118 (61%) females and
      75 (39%) males with a median (range) age of 23 (21-41) years. Ninety-eight (51%)
      respondents undertook their placement at a Teaching Hospital, whereas 93 (41%)
      were attached to a District General Hospital. One-hundred forty-three (74%)
      students felt that a four-week attachment had given them a satisfactory exposure
      to General Surgery, and 36 (19%) disagreed. Sixty-eight (53%) students were
      unable to select a single specialty that they would most like to pursue as a
      future career. Of the remainder, 23 (12%) chose general surgery, 24 (12%) chose
      general medicine, and 22 (11%) chose general practice. Seventy-eight (40%)
      students would consider a career in general surgery, and 75 (39%) would not; 40
      (29%) were undecided. The two most popular attractions to general surgery were
      challenging postgraduate training and highly regarded career esteem. The two most
      common disincentives were family considerations and the sacrifice of personal
      time. CONCLUSIONS: Fewer than half of the final year medical students surveyed
      were willing to consider general surgery as a future career choice. Potential
      disincentives should be targeted to promote recruitment into the specialty.

PMID- 18330625
TI  - Efficacy and safety of seprafilm: systematic review and meta-analysis.

PMID- 18330626
TI  - Bedside placement of removable vena cava filters guided by intravascular
      ultrasound in the critically injured.
AB  - BACKGROUND: Bedside placement of removable inferior vena cava filters (RVCF) is
      increasingly used in critically injured patients. The need for fluoroscopic
      equipment and specialized intensive care unit beds presents major challenges.
      Intravascular ultrasound (IVUS) eliminates such problems. The objective of the
      present study was to analyze the safety and feasibility of IVUS-guided bedside
      RVCF placement in critically injured patients. METHODS: Between October 2004 and
      July 2006 47 IVUS-guided RVCF were placed at the bedside. Medical and trauma
      registry records were reviewed. Primary outcome was RVCF-related complications.
      RESULTS: The mean patient age was 41 +/- 19 years, and the mean Injury Severity
      Score was 30 +/- 12. The right common femoral vein was chosen as the site of
      access in 40 patients, and the left common femoral vein was the access site in 7
      patients. The insertion was performed 3.7 +/- 2.5 days after admission. Four
      patients (8.5%) developed common femoral deep vein thrombosis (DVT) and three
      (6%) developed a peripheral pulmonary embolism (PE). Complications related to
      technique were recorded in two patients (4%) and included one misplacement and
      one access site bleeding with no further associated morbidity. Five patients died
      during the hospital stay from issues unrelated to RVCF. Forty-one patients were
      eligible for follow-up. Removal of RVCF was offered only to 8 patients and was
      performed successfully in 4 (10%) at a mean of 130 days (range: 44-183 days).
      CONCLUSIONS: In this study IVUS-guided bedside placement of RVCF was feasible but
      was also associated with complications. Follow-up was poor, and the rate of
      removal disappointingly low, underscoring the need for further exploration of the
      role of RVCF.

PMID- 18330627
TI  - Sphincter-preserving operations following preoperative chemoradiation: an
      alternative to abdominoperineal resection for lower rectal cancer?
AB  - BACKGROUND: Sphincter-preserving operations (SPO) for lower rectal cancer are on
      the rise. In the study reported here, we compared the oncologic outcomes of
      patients who underwent sphincter-preserving operations following preoperative
      chemoradiation for lower rectal cancer with the outcome for patients who
      underwent abdominoperineal resection (APR). METHODS: This prospective study
      included 87 patients who underwent proctectomy with curative intent for locally
      advanced rectal cancer that was located less than 6 cm from the anal verge. Forty
      four patients had APR with no preoperative treatment. Forty-three patients
      underwent concurrent chemoradiation therapy (CCRT) consisting of preoperative 5
      fluorouracil-based chemotherapy and pelvic radiation (4500-5040 cGy); this was
      followed 6 weeks later by surgery (SPO/CCRT). The oncologic outcomes between the
      two groups were compared, and factors affecting survival were evaluated. RESULTS:
      The median follow-up period was 56.2 months. The overall postoperative
      complication rates did not significantly differ between SPO/CCRT and APR (32.6%
      versus 34.2%; p = 0.879). Also, there were no significant differences in the
      overall recurrence rate (20.9% versus 20.5%; p = 0.956) and 5-year overall
      survival rate (70.8% versus 62.9%; p = 0.189) between the two groups. By
      multivariate analysis, only the pathologic N stage was significantly associated
      with overall survival (p < 0.001). CONCLUSIONS: Sphincter-preserving operation
      with CCRT could be another option for the treatment of locally advanced lower
      rectal cancer in patients who are clinically considered for APR, with no
      deterioration of oncologic outcomes. For patients undergoing curative resection
      for lower rectal cancer, the pathologic N stage can provide valuable prognostic
      information about survival.

PMID- 18330628
TI  - Evaluation of breast lymphatic pathways with indocyanine green fluorescence
      imaging in patients with breast cancer.
AB  - BACKGROUND: In patients with early breast cancer, sentinel lymph node biopsy
      (SLNB) has been emerging as a new standard of care. The use of SLNB with a blue
      dye is convenient and safe, but it requires a high level of technical skill.
      Recently, an instrument that can provide fluorescence imaging of lymphatic flow
      has been introduced. In the present study, we analyzed breast lymphatic pathways
      and discussed its potential as a modality to complement the use of SLNB with a
      blue dye. METHODS: Thirty-seven consecutive patients with breast cancer were
      examined. To obtain fluorescence imaging, an invisible near-infrared fluorescence
      imaging system was used. After indocyanine green was subdermally injected in the
      subareolar site and at two sites around the tumor, the subcutaneous lymphatic
      drainage pathway (LDP) was observed. RESULTS: In 27 (72.9%) of the patients, the
      number of LDP from the periareolar area was one or two. In 21(63.6%) of 33
      patients with subdermal injection around the tumor, no LDP was observed from the
      peritumoral area. Lymphatic connection between the peritumoral area and the
      periareolar area was observed very frequently (91.7%). In 26 (70.3%) of the
      patients, multiple routes joined together and only one route was ultimately
      directed to the axilla. Significant correlation was seen between body mass index
      (BMI) and the transit time to the axilla after injection (p = 0.0038).
      Additionally, a significant correlation was seen between the number of LPD from
      the periareolar area and the distance between detected SLNs and the fluorescence
      line-disappearing point (p = 0.034). CONCLUSIONS: This instrument can provide
      some important information, and can be an available and reliable navigator for
      SLNB with a blue dye.

PMID- 18330629
TI  - Combined major hepatectomy and pancreaticoduodenectomy for biliary cancer:
      challenging procedure in the most experienced centers.

PMID- 18330630
TI  - Perforation of jejunal diverticula in steroids and nonsteroidal anti-inflammatory
      drug abusers: a case series.
AB  - INTRODUCTION: Jejunal diverticula are rare lesions, and when complications arise,
      they pose diagnostic difficulties. Perforation is a common complication resulting
      in an acute abdomen, although preoperative diagnosis is usually not possible. The
      "gold standard" for management for patients with complications is surgery. We
      present a series of patients with perforated jejunal diverticula who were on
      prolonged treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and
      steroids for Chikungunya fever. METHODS: There were a total of six patients, all
      of them presenting with perforative peritonitis, with or without shock. Plain
      abdominal radiogram and ultrasonogram confirmed this, although the exact site of
      the perforation was not diagnosed preoperatively. All patients underwent
      exploratory laparotomy and perforated jejunal diverticulum was found. Resection
      and anastomosis was performed in all cases. RESULTS: The mean operating time was
      113.5 minutes, and the blood loss was not significant. Postoperative course was
      uneventful except wound infection in two patients. There was no mortality.
      CONCLUSIONS: Prolonged NSAID and steroid use are known to cause
      ulceration/perforation of the upper digestive tract and colonic diverticula. This
      seems to be the most likely cause for the perforation of jejunal diverticula in
      our series of patients. This view is supported by the absence of inflammation and
      infiltration of neutrophils on histopathological examination of the diverticula.

PMID- 18330631
TI  - Comparison of ultrasonography-guided central venous catheterization between adult
      and pediatric populations.
AB  - The purpose of this study was to compare the technical success and complication
      rates of ultrasonography-guided central venous catheterization between adult and
      pediatric patients which have not been reported previously. In a 4-year period,
      859 ultrasonography-guided central vein catheterizations in 688 adult patients
      and 247 catheterizations in 156 pediatric patients were retrospectively
      evaluated. Mean age was 56.3 years (range, 18 to 95 years) for adults and 3.3
      years (range, 0.1 to 16.3 years) for children. The preferred catheterization site
      was internal jugular vein in 97% of adults and 85% of children. The technical
      success rate, mean number of punctures, and rate of single wall puncture were
      99.4%, 1.04 (range, 1-3), and 83% for adults and 90.3%, 1.25 (range, 1-5), and
      49% for children, respectively. All the differences were statistically
      significant (p < 0.05). Complication rates were 2.3% and 2.4% for adults and
      children, respectively (p > 0.05). Major complications such as pneumothorax and
      hemothorax were not seen in any group. In conclusion, ultrasonography-guided
      central venous catheterization has a high technical success rate, lower puncture
      attempt rate, and higher single wall puncture rate in adults compared to
      children. Complication rates are comparable in the two groups.

PMID- 18330632
TI  - Rhamnolipid-biosurfactant permeabilizing effects on gram-positive and gram
      negative bacterial strains.
AB  - The potential of biosurfactant PS to permeabilize bacterial cells of Pseudomonas
      aeruginosa, Escherichia coli, and Bacillus subtilis on growing (in vivo) and
      resting (in vitro) cells was studied. Biosurfactant was shown to have a neutral
      or detrimental effect on the growth of Gram-positive strains, and this was
      dependent on the surfactant concentration. The growth of Gram-negative strains
      was not influenced by the presence of biosurfactant in the media. Cell
      permeabilization with biosurfactant PS was shown to be more effective with B.
      subtilis resting cells than with Pseudomonas aeruginosa. Scanning-electron
      microscopy observations showed that the biosurfactant PS did not exert a
      disruptive action on resting cells such that it was detrimental to the effect on
      growing cells of B. subtilis. Low critical micelle concentrations, tender action
      on nongrowing cells, and neutral effects on the growth of microbial strains at
      low surfactant concentrations make biosurfactant PS a potential candidate for
      application in different industrial fields, in environmental bioremediation, and
      in biomedicine.

PMID- 18330633
TI  - Resistance to simulated gastrointestinal conditions and adhesion to mucus as
      probiotic criteria for Bifidobacterium longum strains.
AB  - Eight Bifidobacterium longum strains, including reported probiotic strains
      (commercial and noncommercial), collection strains, and laboratory isolates, were
      investigated for their ability to adhere to mucin as well as their ability to
      tolerate acid and bile. Strains could be discriminated based on their sensitivity
      at pH values of 2.0 to 2.5 and bile concentrations of 0.5% to 2.0%. B. longum NCC
      2705, a strain known for its probiotic properties, showed the highest resistance
      to gastrointestinal conditions, whereas the commercial probiotic strains B.
      longum BB 536 and SP 07/3 were the least resistant. In parallel, the human
      isolate B. longum BIF 53 showed the highest adhesion to mucin, whereas the
      commercial probiotic strains B. longum W 11, BB 536, and SP 07/3 were the least
      adhesive. The bacterial adhesion to mucin of strains B. longum NCC 2705 and BIF
      53 could be reduced by lysozyme, indicating that cell-wall components are
      involved in the adhesion process. These results showed that there is no obvious
      link between adhesion and resistance to gastrointestinal conditions and the
      probiotic status of the studied strains. This calls for a definition of
      conditions for in vitro tests that better predict the in vivo functionality of
      probiotic strains.

PMID- 18330634
TI  - Impact of dexamethasone-induced immunosuppression on the duration and level of
      shedding of Escherichia coli O157:H7 in calves.
AB  - The goal of this study was to determine whether immunosuppression plays a role in
      the level and duration of fecal shedding of Escherichia coli O157.
      Immunosuppression was induced in calves by administering dexamethasone. Six 1
      week-old Holstein bull calves were injected intramuscularly with dexamethasone
      and orally inoculated with 10(9) CFU of a mixture of three nalidixic-acid
      resistant strains of E. coli O157:H7. Five 1-week-old Holstein bull calves that
      were given the same oral inoculation of E. coli O157:H7, but not the
      dexamethasone injections, served as controls. All calves were examined daily and
      fecal samples were collected three times a week for detection and enumeration of
      the nalidixic-acid resistant E. coli O157. Four weeks after the last calf stopped
      shedding, all calves were necropsied and samples from the gastrointestinal tract
      were taken for the detection of the nalidixic-acid resistant E. coli O157.
      Dexamethasone-injected calves shed at higher levels (P = 0.04) on days 4 and 7
      postinoculation, but not thereafter. None of the samples collected at necropsy
      were positive for E. coli O157. Data from this study suggest that there may be a
      time-dependent relationship between dexamethasone immunosuppression and the fecal
      concentration of E. coli O157 but that transient immunosuppression does not
      appear to prolong shedding of E. coli O157.

PMID- 18330635
TI  - Diesel and kerosene degradation by Pseudomonas desmolyticum NCIM 2112 and
      Nocardia hydrocarbonoxydans NCIM 2386.
AB  - Pseudomonas desmolyticum NCIM 2112 (Pd 2112) and Nocardia hydrocarbonoxydans NCIM
      2386 (Nh 2386) demonstrated an ability to degrade diesel and kerosene. Triton X
      100 had enhanced the diesel degradation process by reducing the time required for
      the maximum utilization of total petroleum hydrocarbon. Fourier transform
      infrared spectroscopy spectrum of degraded diesel indicates the presence of
      aliphatic and aromatic aldehydes, C=C aromatic nuclei, and substituted benzenes.
      Surface tension reduction and stable emulsification was increased using
      consortium when compared to individual strains. Triton X-100 showed increase in
      microbial attachment to hydrocarbon among the various chemical surfactants
      tested. For generating a rapid assay to screen microorganisms capable of
      degrading kerosene, the acetaldehyde produced in the degradation process could be
      used as an indicator of degradation. These results indicate diesel and kerosene
      degradation ability of both of the strains.

PMID- 18330636
TI  - Role of CheY1 and CheY2 in the chemotaxis of A. tumefaciens toward
      acetosyringone.
AB  - Agrobacterium tumefaciens has a chemtaxis operon, which includes orf1, orf2,
      cheY1, cheA, cheR, cheB, cheY2, orf9, and orf10. In-frame deletions of cheY1 and
      cheY2 were constructed and the chemosensory behavior of the mutants was examined
      on swarm plates and in a chemotaxis assay toward acetosyringone. The cheY2 mutant
      (C1/delY2) showed impaired chemotactic capabilities in both swarming and
      chemotaxis assays. The effect of lacking CheY1 on chemotaxis is less severe than
      that of CheY2, under the conditions studied.

PMID- 18330637
TI  - Occurrence of resistance to antibiotics, UV-B, and arsenic in bacteria isolated
      from extreme environments in high-altitude (above 4400 m) Andean wetlands.
AB  - High-altitude Andean wetlands are pristine environments with extreme conditions
      such as high UV radiation, high heavy metal content (mainly arsenic), high
      salinity, and oligotrophy. In this paper, the UV-B resistance and tolerance to
      arsenic of phylogenetically characterized bacteria (Actinobacteria [six
      isolates], Firmicutes [four isolates], and gamma-Proteobacteria [three isolates])
      isolated from Laguna Vilama (4400-m altitude) and Laguna Azul (4560 m) were
      determined. In addition, given that multiple antibiotic resistances were also
      determined, a relationship between antibiotic resistances as a consequence of
      mutagenic ability or in relation to metal resistance is proposed. High UV-B
      resistances were found, since after 30 min (0.7 KJ m(-2)) and 60 min (1.4 KJ m(
      2)) of irradiation, most of the studied bacteria did not show a decreased
      survival; what is more, many of them had an improved survival with the increased
      doses. Augmentations in mutagenesis rates were observed after UV-B irradiation in
      only 4 of the 13 tested isolates. Arsenite tolerance was also established in 8 of
      the 13 tested strains: Staphylococcus saprophyticus A3 and Micrococcus sp. A7,
      which were able to grow in media containing up to 10 mM As(III). Finally,
      predominance of antibiotic resistances (azithromycin, erythromycin,
      clarithromycin, roxithromycin, streptomycin, chloramphenicol, gentamycin,
      kanamycin, tetracycline, and ampicillin) was found, in all the isolated strains
      from both wetlands, with unexpectedly high minimal inhibitory concentrations
      (MICs; >2 mg mL(-1)) for macrolides. These results demonstrate that in extreme
      environments like high-altitude wetlands there is a correlation of
      multiresistances to UV-B radiation and arsenic, and that antibiotic resistances
      are also widespread in these pristine environments, where antibiotic selective
      pressure is supposed to be absent.

PMID- 18330638
TI  - Increased risk of both ulcerative colitis and Crohn's disease in a population
      suffering from COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by chronic
      inflammation of the airways. In the majority of cases, the inflammation is
      triggered by tobacco smoke. Smoking also affects the pathogenesis of inflammatory
      bowel disease (IBD), protecting against ulcerative colitis (UC) and promoting
      development of Crohn's disease (CD). The present study was undertaken to
      investigate occurrence of IBD among COPD patients, indicating common inflammatory
      pathways and shared vulnerability on a genetic basis. The study was designed as a
      population-based cohort study. All individuals discharged with a diagnosis of
      COPD from 1987 to 2002 were identified in the Swedish Inpatient Register
      (n=180,239). Controls and first-degree relatives of both cases and controls were
      identified using the Multi-Generation Register. Finally, all individuals
      (n=1,174,557) were compared with the Inpatient Register, identifying discharges
      with a diagnosis of UC or CD. Hazard ratios (HR) for IBD were determined by Cox
      proportional hazards regression analysis. COPD patients had a significantly
      higher risk of both UC (HR 1.83; 95% CI 1.61-2.09) and CD (HR 2.72; 95% CI 2.33
      3.18). Among first-degree relatives of COPD patients, there was also an overall
      increased risk of CD (HR 1.25; 95% CI 1.09-1.43) but not of UC (HR 1.09; 95% CI
      0.96-1.23). The kinship of first-degree relatives displayed an increased risk of
      both UC and CD among siblings (HR 1.49; 95% CI 1.15-1.91 and HR 1.46; 95% CI 1.12
      1.89, respectively). The results suggest that COPD and IBD may have inflammatory
      pathways in common, including genetic variants of genes predisposing for disease.

PMID- 18330639
TI  - Plasminogen activator inhibitor-1 in obstructive sleep apnea patients with and
      without hypertension.
AB  - Obstructive sleep apnea syndrome (OSAS) is an important risk factor in
      cardiovascular disorders. Although the precise mechanism remains to be described,
      hypercoagulability seems to be involved. To test the presence of decreased
      fibrinolysis, we measured plasma levels of plasminogen activator inhibitor-1 (PAI
      1) in 96 male subjects (32 subjects with OSAS, 32 subjects with both OSAS and
      hypertension, and a 32 subjects in the control group). All subjects completed a
      sleep questionnaire and underwent a general physical examination, biochemistry
      test, and polysomnography study. Patients and control subjects had similar
      baseline clinical characteristics for age, gender, smoking habit, and levels of
      cholesterol and triglycerides. Patients with OSAS presented significantly higher
      circulating levels of PAI-1 compared with the control group, and the difference
      was even more marked in patients with both OSAS and hypertension. OSAS patients
      presented a significant inverse correlation between PAI-1 levels and apnea
      hypopnea index (r= -0.71, p<0.001). In conclusion, OSAS patients presented higher
      circulating levels of PAI than the control group, which was even greater when
      patients had associated hypertension.

PMID- 18330640
TI  - Do recurrences after paraesophageal hernia repair matter? : Ten-year follow-up
      after laparoscopic repair.
AB  - BACKGROUND: The recurrence rate for paraesophageal hernias (PEH) can be as high
      as 30% following laparoscopic repair. The aim of this study was to determine the
      severity of symptoms in patients with recurrences and the need for reoperation 10
      years after surgery. METHODS AND PROCEDURES: Consecutive laparoscopic
      paraesophageal cases performed at a single institution between 1993 and 1996 were
      identified from the institution's foregut database. Patients were asked about the
      presence and severity of symptoms (heartburn, chest pain, regurgitation, and
      dysphagia). Patients were also asked whether they had (1) been diagnosed with
      hernia recurrence or (2) undergone repeat surgical intervention. RESULTS:
      Complete follow-up was obtainable in 31 of the total of 52 patients (60%). The
      proportion of patients reporting moderate/severe symptoms was less at 10 years
      than preoperatively: heartburn 12% versus 54% (p < 0.001), chest pain 9% versus
      36% (p = 0.01), regurgitation 6% versus 50% (p < 0.001), and dysphagia 3% versus
      30% (p = 0.001). Two patients underwent repeat surgical intervention for
      symptomatic recurrences within the first postoperative year. Eight more patients
      have been diagnosed with hernia recurrences on either contrast esophagram or
      upper endoscopy but had not required reoperation. At ten years, more patients
      with hernia recurrence had heartburn than those who did not have recurrences (60%
      versus 14%; p < 0.05). CONCLUSIONS: Despite a hiatal hernia recurrence rate of
      32% 10 years after surgery, laparoscopic PEH was a successful procedure in the
      majority of patients; most remained symptomatically improved and required no
      further intervention 10 years after surgery.

PMID- 18330642
TI  - Abstracts of the 2008 Scientific Session of the Society of American
      Gastrointestinal and Endoscopic Surgeons (SAGES), Philadelphia, Pennsylvania,
      USA, 9-12 April 2008.

PMID- 18330643
TI  - Spectral diversity of fluorescent proteins from the anthozoan Corynactis
      californica.
AB  - Color morphs of the temperate, nonsymbiotic corallimorpharian Corynactis
      californica show variation in pigment pattern and coloring. We collected seven
      distinct color morphs of C. californica from subtidal locations in Monterey Bay,
      California, and found that tissue- and color-morph-specific expression of at
      least six different genes is responsible for this variation. Each morph contains
      at least three to four distinct genetic loci that code for these colors, and one
      morph contains at least five loci. These genes encode a subfamily of new GFP-like
      proteins, which fluoresce across the visible spectrum from green to red, while
      sharing between 75% to 89% pairwise amino-acid identity. Biophysical
      characterization reveals interesting spectral properties, including a bright
      yellow protein, an orange protein, and a red protein exhibiting a "fluorescent
      timer" phenotype. Phylogenetic analysis indicates that the FP genes from this
      species evolved together but that diversification of anthozoan fluorescent
      proteins has taken place outside of phylogenetic constraints, especially within
      the Corallimorpharia. The discovery of more examples of fluorescent proteins in a
      non-bioluminescent, nonsymbiotic anthozoan highlights possibilities of adaptive
      ecological significance unrelated to light regulation for algal symbionts. The
      patterns and colors of fluorescent proteins in C. californica and similar species
      may hold meaning for organisms that possess the visual pigments to distinguish
      them.

PMID- 18330644
TI  - Laparoscopic resection of rectal cancer: a comparison of surgical and oncologic
      outcomes between extraperitoneal and intraperitoneal disease locations.
AB  - PURPOSE: The extraperitoneal rectum is anatomically and biologically different
      from the intraperitoneal rectum, therefore, the surgical outcomes may be
      different. This study was designed to assess operative outcomes of laparoscopic
      resection of extraperitoneal (< or = 7 cm from the anal verge) vs.
      intraperitoneal rectal cancer. METHODS: Prospective data were collected from 312
      patients with rectal cancer who underwent laparoscopic resection. Patients were
      divided into two groups: extraperitoneal (EP, n = 138) vs. intraperitoneal (IP, n
      = 174). Mean follow-up was 33 months. RESULTS: Patients with pT3/pT4 accounted
      for 69.6 percent of EP and 74.1 percent of IP. Circumferential margin was
      positive in 8.7 percent of EP and 0.6 percent of IP (P = 0.0004). Anastomotic
      leakage developed in 9.7 percent of EP vs. 4.6 percent of IP (P = 0.1081, overall
      6.4 percent). Local recurrence rate at three years was 7.6 percent in EP and 0.7
      percent in IP (P = 0.0011, overall 4 percent). By multivariate analysis,
      extraperitoneal location was a risk factor for local recurrence. CONCLUSIONS:
      Laparoscopic resection of rectal cancer, regardless of EP or IP, provided
      acceptable operative outcomes. There was an increasing tendency for positive
      circumferential margin, leakage, and local recurrence in EP vs. IP. A
      multicenter, prospective study is ongoing to identify the high-risk group for
      local recurrence who may really benefit from neoadjuvant therapy in the era of
      laparoscopy.

PMID- 18330646
TI  - Vacuum-assisted closure for the treatment of parastomal skin necrosis: a novel
      approach to an unusual complication. Report of a case.
AB  - Extensive peristomal skin necrosis is an unusual complication, which is difficult
      to manage because of frequent contamination from the stoma site. This wound leads
      to difficulty in applying the stoma appliance. This case report describes the
      successful use of the vacuum-assisted closure system in the management of a
      patient who developed peristomal skin necrosis after emergency Hartmann's
      procedure.

PMID- 18330647
TI  - PET/CT colonography for the preoperative evaluation of the colon proximal to the
      obstructive colorectal cancer.
AB  - PURPOSE: This study was designed to evaluate the usefulness of 18
      fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT)
      colonography in preoperative diagnosis of the tumors proximal to obstructive
      colorectal cancers, which were defined as cancers that cannot be traversed
      colonoscopically. METHODS: A whole-body PET/CT protocol for tumor staging and a
      protocol for CT colonography were integrated into one examination. No cathartic
      bowel preparation was used before this examination. Thirteen prospective patients
      with obstructive cancer were examined. We compared the detection rates for
      obstructive colorectal cancers and tumors proximal to the obstruction using air
      inflated PET/CT colonography to intraoperative examinations, histopathologic
      outcome, and follow-up colonoscopy. RESULTS: PET/CT colonography correctly
      identified all 13 primary obstructive colorectal cancers and all 2 synchronous
      colon cancers proximal to the obstruction. The two synchronous colon cancers
      detected at PET/CT colonography were confirmed and removed at single-stage
      surgical procedures. PET/CT colonography was able to localize all colorectal
      cancers precisely. There were no false-negative or false-positive proximal
      colorectal cancers by PET/CT colonography. Other preoperative examinations missed
      the synchronous colon cancers. CONCLUSIONS: In patients with obstructive
      colorectal cancers, preoperative PET/CT colonography provided valuable anatomic
      and functional information of the entire colon to properly address surgery of
      colorectal cancer.

PMID- 18330648
TI  - Closure mechanism of the anal canal in women: assessed by three-dimensional
      ultrasound imaging.
AB  - PURPOSE: To describe the functional correlates of anal canal anatomy using 3
      dimensional ultrasound imaging. METHODS: Ten nulliparous women were studied by
      using a 10-cm bag of 20-mm diameter. The bag was placed along the anal canal and
      inflated with 20 to 45 ml water, in 5-ml increments. At each volume, a three
      dimensional ultrasound volume of the anal canal was obtained while the subjects
      were at rest and squeeze. The ultrasound images were analyzed to determine the
      relationship between the bag cross-sectional area and bag pressure. RESULTS: At
      low distension volumes, the bag is shaped like an "hourglass." The flared ends of
      the funnels correspond with the proximal and distal margins of the puborectalis
      muscle and external anal sphincter respectively. With increasing bag volumes, the
      length of completely closed segment of anal canal decreased. The last anal
      segment to open at rest was the one surrounded by all three structures. Anal
      contraction resulted in reduction of the anal canal cross-sectional area; the
      least compliant part of the anal canal was the one surrounded by external anal
      sphincter. CONCLUSION: The internal anal sphincter, external anal sphincter, and
      puborectalis muscle are all involved in the anal canal closure function. During
      contraction, the external anal sphincter is the strongest component of anal canal
      closure mechanism.

PMID- 18330649
TI  - Collagen fistula plug for the treatment of anal fistulas.
AB  - PURPOSE: This study was designed to evaluate the efficacy of the Surgisis (Anal
      Fistula Plug) in multiple patients at our institution and present early clinical
      results along with notable clinical observations from our experience. METHODS:
      This was a prospective analysis of all patients who received the Anal Fistula
      Plug for treatment of anorectal fistulas between April 2006 and February 2007.
      All tracts were irrigated with peroxide, the plug was inserted in the tract, and
      buried at the internal opening with 2-0 vicryl and mucosal advancement flap.
      Statistical analysis was performed with Fisher's exact test. RESULTS: Forty-five
      patients were treated with the Anal Fistula Plug and one patient was lost to
      follow-up. There were 27 males and 17 females with average age of 44.1 years
      treated for simple (n = 24) or complex (n = 20) fistulas. Preliminary results
      indicated an 84 percent healing rate by 3 to 8 weeks postoperatively, which
      progressively declined from 72.7 percent at 8 weeks to 62.4 percent at 12 weeks
      and 54.6 percent at a median follow-up of 6.5 (range, 3-13) months. Long-term
      Anal Fistula Plug closure rate was significantly higher in patients with simple
      than complex fistulas (70.8 vs. 35 percent; P < 0.02) and with non-Crohn's
      disease vs. Crohn's disease (66.7 vs. 26.6 percent; P < 0.02). Patients with two
      successive plug placements had significantly lower closure rates than patients
      who underwent placement of the plug once (12.5 vs. 63.9 percent; P < 0.02). No
      significant difference in closure rates were found between patients with one vs.
      multiple fistula tracts. Postoperative complications included perianal abscess in
      five patients (3 Crohn's disease, 2 non-Crohn's disease). CONCLUSIONS: Anal
      Fistula Plug is most successful in the treatment of simple anorectal fistulas but
      is associated with a high failure rate in complex fistula and particularly in
      patients with Crohn's disease. Repeat plug placement is associated with increased
      failure. Given the relatively low morbidity associated with the procedure, Anal
      Fistula Plug should be considered as a first-line treatment for patients with
      simple fistulas and as an alternative in selected patients with complex fistulas.

PMID- 18330650
TI  - Management of the axilla in women with breast cancer: current clinical practice
      and a new selective targeted approach.
AB  - BACKGROUND: Axillary nodal status is the most important prognostic factor for
      patients with breast cancer. Clinical assessment and imaging modalities are not
      always reliable. Surgical removal and histopathological examination of axillary
      lymph nodes remain essential methods of staging the axilla. However, the optimal
      management of the axilla remains uncertain. METHODS: We performed Medline
      searches to identify relevant systematic reviews, meta-analysis, and
      nonrandomized and randomized controlled trials for the past 5 years (up to
      December 2007), as well as important historical articles and clinical guidelines
      relating to management of the axilla in women with breast cancer. RESULTS:
      Axillary lymph node dissection (ALND) has been the standard surgical approach for
      many years. It is, however, associated with marked morbidity; survival benefit
      remains uncertain. Axillary node sampling, widely practiced in the United
      Kingdom, is a reliable alternative procedure in staging the axilla, with less
      morbidity. Sentinel lymph node biopsy (SLNB) has become an accurate method for
      staging the axilla in women with operable, clinically node-negative breast
      cancer. SLNB alone appears to be a safe and acceptable procedure for patients
      with uninvolved SLNs. Completion ALND or axillary radiotherapy remains the
      standard treatment for patients with tumor-involved SLNs. SLNB is associated with
      less morbidity than ALND. However, long-term follow-up and therapeutic outcomes
      are being awaited from randomized controlled trials. CONCLUSIONS: Several
      procedures are available for staging and treating the axilla. A tailored surgical
      approach, with careful assessment of risk-benefit and patient preference, is
      guiding the evolving modern management of the axilla for women with breast
      cancer.

PMID- 18330651
TI  - Radiofrequency ablation versus resection for resectable colorectal liver
      metastases: time for a randomized trial?

PMID- 18330652
TI  - Isolated limb perfusion and external beam radiotherapy for soft tissue sarcomas
      of the extremity: long-term effects on normal tissue according to the LENT-SOMA
      scoring system.
AB  - BACKGROUND: With the combined treatment procedure of isolated limb perfusion
      (ILP), delayed surgical resection and external beam radiotherapy (EBRT) for
      locally advanced soft tissue sarcomas (STS) of the extremities, limb salvage
      rates of more than 80% can be achieved. However, long-term damage to the healthy
      surrounding tissue cannot be prevented. We studied the late effects on the normal
      tissue using the LENT-SOMA scoring system. PATIENTS AND METHODS: A total of 32
      patients-median age 47 (range 14-71) years-were treated for a locally advanced
      STS with ILP, surgical resection and often adjuvant 60-70 Gy EBRT. After a median
      follow-up of 88 (range 17-159) months, the patients were scored, using the LENT
      SOMA scales, for the following late tissue damage: muscle/soft tissue, peripheral
      nerves, skin/subcutaneous tissue and vessels. RESULTS: According to the
      individual SOM parameters of the LENT-SOMA scales, 20 patients (63%) scored grade
      3 toxicity on one or more separate items, reflecting severe symptoms with a
      negative impact on daily activities. Of these patients, 3 (9%) even scored grade
      4 toxicity on some of the parameters, denoting irreversible functional damage
      necessitating major therapeutic intervention. CONCLUSIONS: In evaluating long
      term morbidity after a combined treatment procedure for STS of the extremity,
      using modified LENT-SOMA scores, two-thirds of patients were found to have
      experienced serious late toxic effects.

PMID- 18330653
TI  - Update in pain medicine.

PMID- 18330654
TI  - Health literacy, cognitive abilities, and mortality among elderly persons.
AB  - BACKGROUND: Low health literacy and low cognitive abilities both predict
      mortality, but no study has jointly examined these relationships. METHODS: We
      conducted a prospective cohort study of 3,260 community-dwelling adults age 65
      and older. Participants were interviewed in 1997 and administered the Short Test
      of Functional Health Literacy in Adults and the Mini Mental Status Examination.
      Mortality was determined using the National Death Index through 2003.
      MEASUREMENTS AND MAIN RESULTS: In multivariate models with only literacy (not
      cognition), the adjusted hazard ratio was 1.50 (95% confidence of interval [CI]
      1.24-1.81) for inadequate versus adequate literacy. In multivariate models
      without literacy, delayed recall of 3 items and the ability to serial subtract
      numbers were associated with higher mortality (e.g., adjusted hazard ratios [AHR]
      1.74 [95% CI 1.30-2.34] for recall of zero versus 3 items, and 1.32 [95% CI 1.09
      1.60] for 0-2 vs 5 correct subtractions). In multivariate analysis with both
      literacy and cognition, the AHRs for the cognition items were similar, but the
      AHR for inadequate literacy decreased to 1.27 (95% CI 1.03 - 1.57). CONCLUSIONS:
      Both health literacy and cognitive abilities independently predict mortality.
      Interventions to improve patient knowledge and self-management skills should
      consider both the reading level and cognitive demands of the materials.

PMID- 18330655
TI  - Improved survival following right trisectionectomy with caudate lobectomy without
      operative mortality: surgical treatment for hilar cholangiocarcinoma.
AB  - BACKGROUND: We conducted this study to assess the safety of performing right
      trisectionectomy with caudate lobectomy for hilar cholangiocarcinoma by analyzing
      postoperative mortality and morbidity, and to evaluate the effect of such
      procedure on pathological curability and long-term overall survival. METHODS: A
      retrospective clinicopathological analysis was performed for 16 hilar
      cholangiocarcinoma patients who underwent right trisectionectomy with caudate
      lobectomy from June 1999 to April 2003. The median follow-up period was 36.9
      months. The preoperative Bismuth-Corlette type was type II in four patients, type
      III(A) in 10 patients, and type IV in two patients. RESULTS: The median liver
      volume after hepatic resection was 21.9% of the total liver volume. Postoperative
      complications including one chronic liver failure developed in 12 patients, but
      no in-hospital deaths occurred. A postoperative pathological examination showed a
      cancer free margin in all of the proximal resection sites, although three cases
      had carcinoma in situ (CIS) lesions in the distal margin that were confirmed
      during surgery. The 1-, 3-, and 5-year overall survival rates were 94.1%, 64.2%,
      and 64.2%, respectively. CONCLUSION: We obtained excellent survival rates without
      any in-hospital deaths following right trisectionectomy with caudate lobectomy.
      This procedure may be an effective surgical procedure that can be executed to
      achieve low mortality rate and high pathological curability for hilar
      cholangiocarcinomas, except for Bismuth type III(B).

PMID- 18330656
TI  - Serum paraoxonase undergoes inhibition and proteolysis during experimental acute
      pancreatitis.
AB  - Oxidative stress has a primary role in the pathogenesis of severe acute
      pancreatitis. Then, the antioxidant capacity is a critical factor in the
      progression of this disease. Serum paraoxonase-1 (PON1) is an esterase associated
      with high-density lipoprotein, which clinical interest resides in its ability to
      prevent or limit the lipid oxidation. The aim of this study was to investigate
      changes in PON1 activity in the early stages of acute pancreatitis and to find
      out if its alteration is related with the severity of the disease. To this
      purpose, we used an experimental model of taurocholate-induced mild and severe
      acute pancreatitis. Our results showed that serum activity and PON1 concentration
      decreased 18 h after the induction of a severe acute pancreatitis. In vitro
      analysis revealed that incubation with oxidized lipids obtained from pancreatitis
      samples results in the inactivation of the enzyme in a concentration-dependent
      manner. In addition to oxidative inactivation, we observed by Western blot, an
      immunoreactive band suggestive of proteolytic degradation of the enzyme,
      altogether indicating that during severe acute pancreatitis, there is a
      significant decrease in serum PON1 activity. This decrease is related with
      inactivation of the enzyme by oxidized lipids, probably followed by proteolytic
      degradation of the enzyme.

PMID- 18330657
TI  - Treatment of hemorrhoids in day surgery: stapled hemorrhoidopexy vs Milligan
      Morgan hemorrhoidectomy.
AB  - BACKGROUND: Recently, it has been demonstrated that surgical treatment of
      hemorrhoids in a day-care basis is possible and safe. The aim of this study was
      to compare the Longo stapled hemorrhoidopexy (SH) and the Milligan-Morgan
      hemorrhoidectomy (MMH). METHODS: One hundred seventy one patients (95 cases in SH
      group and 76 cases in MMH group) entered the study: 83 cases were III degree
      hemorrhoids, 88 IV degree. A priori and a post hoc power analysis were performed.
      Results, prospectively collected, were compared using chi squared test and
      student t test. Visual analog scale was used for pain evaluation. Postoperative
      pain, duration of pain, wound secretion, bleeding, resumption of a normal
      lifestyle, and postoperative complication were evaluated. RESULTS: Surgical time
      was 28.41+/-10.78 for MMH and 28.30+/-13.28 min in SH (P=0.94). Postoperative
      pain was not different between MMH and SH during the first two postoperative days
      (4.73+/-2.91 vs 5.1+/-3.048; P=0.4), during the following 6 days, patients
      treated with SH had less pain (4.63+/-2.04 in MMH vs 3.60+/-2.35 in SH; P=0.006).
      In the SH group, seven patients needed further hospital stay for complicated
      course. SH showed higher incidence of anal fissure compared with MMH (6.3% vs 0%;
      P=0.025) but no differences in urinary retention, anal stricture, urgency, or
      anal hemorrhage. CONCLUSIONS: This study confirms that SH is associated with less
      postoperative pain and shorter postoperative symptoms, compared with MMH. SH may
      be a viable addition to the therapy for hemorrhoids with some advantages in early
      postoperative pain and some disadvantages in postoperative complications and
      costs.

PMID- 18330658
TI  - Incarcerated umbilical hernia in a super-super-obese patient.
AB  - Abdominal wall hernias are more prevalent in the morbidly obese. Incarceration of
      external hernias is a relatively common process in adults and is associated to a
      high rate of complications and mortality. We present the case of a morbidly super
      super-obese patient (body mass index, 80 kg/m(2)) who underwent emergency surgery
      for an incarcerated umbilical hernia; the patient died despite segmental
      intestinal resection, hernia repair using mesh, and intensive care.

PMID- 18330659
TI  - Cardiac arrest following adjustment of a gastric band.
AB  - Laparoscopic adjustable gastric banding is an established and popular technique
      for achieving weight loss in the morbidly obese. It is however not without risks
      of morbidity and even mortality. The authors present a case report of a 46-year
      old female who had a cardiac arrest after adjustment of a gastric band. The
      pathomechanisms to explain this event are explored and a review of the available
      literature is undertaken.

PMID- 18330660
TI  - Clinical characteristics and outcome of morbidly obese bariatric patients with
      concurrent hepatitis B viral infection.
AB  - BACKGROUND: Bariatric surgery is the only effective and long-lasting treatment of
      morbidly obese patients. However, the safety and efficacy of bariatric surgery in
      patients with hepatitis B viral (HBV) infection is not clear. The aim of the
      present study is to investigate whether HBV infection influences clinic features
      and outcomes of bariatric surgery. METHODS: The preoperative seropositivity of
      HBV surface antigen (HBsAg) using radioimmunoassay was determined in 592 patients
      (481 female, 111 male: mean age 30.5 +/- 8.1 years; mean body mass index [BMI]
      43.1 +/- 6.0) who had undergone bariatric surgery (209 banding and 383 gastric
      bypass) for their morbid obesity in the past 5 years. All the clinical data were
      prospectively collected and stored. RESULTS: The overall seroprevalence of HbsAg
      was 18.8%. Morbidly obese patients positive for HBV infection were associated
      with older age and higher diastolic blood pressure, but not with sex, BMI, liver
      enzyme, blood lipid, and glucose levels. Although minigastric bypass (MGB) had a
      better weight reduction than gastric banding, there was no difference in weight
      reduction between patients who were positive and negative for HBV infection. The
      weight loss curves and resolution of obesity-related comorbidities were similar
      between the two groups except the postoperative aspartate transaminase (AST) and
      alanine transaminase (ALT) were significantly higher in patients who were
      positive for HBV infection. During follow-up, two patients developed fulminating
      hepatitis after MGB with one mortality. CONCLUSION: Morbidly obese patients with
      the existence of HBV infection do not influence the outcome of bariatric surgery,
      but continuing monitor of the liver function is indicated.

PMID- 18330661
TI  - Potential applications of global protein expression analysis (proteomics) in
      morbid obesity and bariatric surgery.
AB  - Global protein expression analysis, known as proteomics, has emerged as a novel
      scientific technology currently successfully applied to several fields of
      medicine including cancer and transplantation. Thereby, a thorough exploration of
      the pathogenic mechanisms and a better understanding of the pathophysiology of
      diseases as well as identification of diagnostic biomarkers have been achieved.
      In this paper, we outline the basic principles and potential applications of this
      promising tool in bariatric surgery where proteomics might hold great potential
      for new insights into diagnostic and therapeutic decision making based on
      improved knowledge of metabolic regulations pre- and postsurgical interventions
      in morbidly obese patients.

PMID- 18330662
TI  - Bariatric surgery can correct iron depletion in morbidly obese women: a link with
      chronic inflammation.
AB  - BACKGROUND: Obesity is associated with a chronic and low-grade inflammation which
      may cause hypoferremia as seen in patients with chronic inflammatory diseases.
      The aim of the present study was to investigate the relationship between iron
      status and markers of inflammation in morbidly obese women and the effect of
      bariatric surgery. METHODS: Our cohort of patients consisted of 178 morbidly
      obese females selected for bariatric surgery. Clinical and biochemical data were
      recorded before surgery, and histopathological studies were carried out on
      preoperative liver biopsy samples. Fifty-five patients have been followed up
      after bariatric surgery. RESULTS: A high prevalence of iron depletion was present
      in this cohort, with 53% having a transferrin saturation ratio below 0.20. Iron
      depletion was significantly correlated with raised levels of indices of
      inflammation, C-reactive protein (CRP), orosomucoid and haptoglobin), and with
      the white blood cell count. In multivariate analysis, orosomucoid and CRP were
      independently associated with iron depletion. Moreover, 6 months after bariatric
      surgery, inflammation level decreased, which was inversely correlated with the
      increase in transferrin saturation. CONCLUSIONS: Iron depletion is common in
      morbidly obese women. Low-grade chronic inflammation associated with obesity
      could be a modulator of iron uptake and utilization. Bariatric surgery may reduce
      chronic inflammation and improve iron status.

PMID- 18330663
TI  - Long-term followup of vascularized fibular grafting for femoral head necrosis.
AB  - Vascularized fibular grafting has been used for treatment of osteonecrosis of the
      femoral head and although some reports demonstrate successful short- to mid-term
      outcomes, long-term results are still unknown. We retrospectively reviewed 135
      patients (151 hips) who underwent vascularized fibular grafting for osteonecrosis
      of the femoral head. One-hundred and ten patients (124 hips) were followed for a
      minimum 10 years (mean, 13.9 years; range, 10-23.7 years). The mean Harris hip
      score improved from 72 to 88. At the latest followup, we found improved or
      unchanged radiographs in 37 of 59 hips initially Stage II hips and 39 of 65 Stage
      III hips. Thirteen hips (13 patients) (10.5%) failed treatment and underwent
      total hip arthroplasty. The location and size of the necrotic lesion and the
      patient's age influenced long-term survival of the graft. Postoperative
      complications included clawing of the big toe in 17 patients, partial peroneal
      nerve palsy in two, and superficial infection in two. Subtrochanteric fracture
      occurred in two hips. The data suggest free vascularized fibular grafting was
      successful in maintaining joint function and delaying the need for joint
      replacement procedure. Graft survival was associated with the patient's age and
      size and location of the lesion but not etiology and stages of the disease.

PMID- 18330664
TI  - The width:thickness ratio of the patella: an aid in knee arthroplasty.
AB  - Establishing the appropriate size of the patellar implant-bone composite is one
      of the important steps ensuring functional success in arthroplasty.
      Conventionally, the patella is measured intraoperatively and its thickness is
      used to guide the depth of resection. However, in a diseased joint, this may not
      reflect the native patellar thickness. We studied the relationship between the
      patellar thickness and various patellar dimensions on three-dimensional
      reconstructed computed tomographic scans from 37 normal adult knees. Patellar
      width correlated with thickness. The average patellar width:thickness ratio was
      2.0 (standard deviation, 0.106; 95% confidence interval, 1.96-2.03). The
      cartilage thickness was on average 2.5 mm (standard deviation, 1.0). The
      width:thickness ratio was similar in 79 digital radiographs taken before TKA of
      knees without patellofemoral disease (mean, 2.1; standard deviation, 0.28). When
      compared with the two other methods for calculating patellar resection described
      in the literature, the width:thickness ratio was more reliable. The
      width:thickness ratio appears anatomically constant and may be a useful guide for
      estimating premorbid patellar thickness.

PMID- 18330665
TI  - A rare and frequently unrecognised pathology in children: femoral hernia.
AB  - A femoral hernia is the protrusion of the abdominal contents through the femoral
      canal. It accounts for less than 1% of all groin hernias in children and is often
      confused with inguinal hernia or other inguinal pathologies. Preoperative
      misdiagnosis has been reported to be between 40 and 75%. We believe that
      misdiagnosis and mistreatment usually occur due to insufficient physical
      examination, knowledge and experience about childhood femoral hernias. Here, we
      report and discuss the clinical appearance and treatment approach of three
      patients operated with the diagnosis of femoral hernias.

PMID- 18330666
TI  - Abdominal wall hernia repair: a comparison of Permacol and Surgisis grafts in a
      rat hernia model.
AB  - BACKGROUND: This study compared two porcine-derived grafts Permacol (Tissue
      Science Laboratory, Covington, GA, USA) and Surgisis (Cook Surgical, Bloomington,
      IN, USA) in terms of strength of incorporation (SOI), incorporation of host
      tissue, and adhesion formation using a rat model. METHODS: A prospective
      randomized study using 48 Sprague-Dawley rats. A standardized 1.5 x 5 cm fascial
      defect was created and repaired with either Permacol or Surgisis grafts. The rats
      were then sacrificed at 3, 14, 28, or 60 days. The specimens were examined for
      SOI, neovascularization, collagen deposition, collagen organization, and adhesion
      formation. RESULTS: Surgisis had significantly greater SOI than Permacol at 28
      (0.115 vs. 0.0754 Mpa) and 60 days (0.131 vs. 0.635 Mpa). Surgisis had
      significantly more collagen deposition and neovascularization than Permacol at 60
      days. The area of adhesions was not significantly different between Surgisis and
      Permacol. CONCLUSION: Surgisis is superior to Permacol in terms of SOI and tissue
      ingrowth at 60 days. Furthermore, Surgisis strengthened over time whereas
      Permacol decreased in strength.

PMID- 18330667
TI  - Executive performance of depressed suicide attempters: the role of suicidal
      ideation.
AB  - OBJECTIVE: Suicidal ideation has been related to cognitive rigidity whereas
      suicidal behaviour itself was associated with specific executive deficits. Yet it
      remains unclear if a distinct cognitive suicidal phenotype does exist. The aim of
      the present study was to further investigate the role of suicidal thinking for
      the neuropsychological performance in depressive suicide attempters. METHOD:
      Depressive inpatients after a recent suicide attempt, who either had present
      suicidal ideation (n=14) or not (n=15) and healthy controls (n=29) were
      recruited. The groups were assessed by means of executive tasks designed to
      capture impulsive decision-making, and with verbal memory and attention tests.
      Self-rating measures of impulsivity and aggression were further applied. RESULTS:
      Only patients with current suicidal ideation showed executive dysfunctions with
      impaired decision-making being the most salient. Verbal memory and attention were
      reasonably intact in all patients. All patients reported increased aggression.
      CONCLUSION: Suicidal ideation is clearly associated with impaired cognitive
      performance. Our results suggest that executive deficits seen in depressive
      suicide attempters have a state-dependent component.

PMID- 18330668
TI  - Increased NAA and reduced choline levels in the anterior cingulum following
      chronic methylphenidate. A spectroscopic test-retest study in adult ADHD.
AB  - The anterior cingulate cortex (ACC) is crucially involved in executive control of
      attention. Here, seven medication-naive adult patients suffering from attention
      deficit/hyperactivity disorder (ADHD) were studied with 2D (1)H-magnetic
      resonance spectroscopic imaging (MRSI) of the ACC [Brodmann areas 24b'-c' and
      32'] twice, once before initiation of stimulant treatment and once after 5-6
      weeks of methylphenidate. Upon retest, all patients demonstrated marked clinical
      improvement. Analysis of regional brain spectra revealed a significantly
      decreased signal of choline containing compounds as well as increased N-acetyl
      aspartate (NAA) levels following treatment with methylphenidate whereas total
      creatine remained unchanged. Our results add to a growing body of evidence
      implicating the ACC in the pathophysiology of ADHD and suggest that subtle
      structural changes might be associated with aspects of clinical improvement under
      stimulant treatment.

PMID- 18330669
TI  - [Optimization of haemodynamics in the device-therapy].

PMID- 18330670
TI  - [Avoidance of ventricular pacing in patients with sinus node disease or
      intermittent AV block].
AB  - In patients with frequent right ventricular stimulation, worsening of heart
      failure and atrial fibrillation may occur. Avoidance of unnecessary right
      ventricular pacing is a major requirement for pacemaker selection and programming
      in patients with sinus node disease or intermittent AV block. In dual chamber
      pacemakers this goal can be achieved by programming a long AV delay or an AV
      delay hysteresis. Algorithms that allow AAI pacing in a dual chamber pacing mode
      and change to DDD mode in case of high degree AV block are a new attempt to avoid
      unnecessary right ventricular pacing. The article describes various strategies to
      avoid unnecessary ventricular pacing and discusses their advantages and
      disadvantages.

PMID- 18330671
TI  - [Optimized programming during cardiac resynchronization therapy].
AB  - Cardiac resynchronization (CRT) has evolved as a therapeutic add-on tool in
      patients with refractory heart failure. Additional pacing of the left ventricle
      leads to relevant clinical and hemodynamic improvement. Optimized programming of
      these pacing systems may modulate therapeutic efficacy. Optimal atrio-ventricular
      (AV) and ventriculo-ventricular (VV) delay programming is documented to increase
      invasively and non-invasively determined parameters of cardiac hemodynamics. In
      this manuscript different options for determining optimal AV and VV delay are
      discussed and a pragmatic approach to optimize CRT programming is detailed. VV
      delay needs to be optimized as a first step of programming. Different techniques
      may estimate the individual need for sequential ventricular pacing. Especially
      electrocardiographic criteria during right and left ventricular pacing may
      approximate the time-delay for pre-excitation. Delay between aortic and pulmonic
      valve ejection can be determined using Doppler echocardiography may identify
      patients who benefit from sequential pacing. Optimizing AV delay is a domain of
      Doppler echocardiography where using a simple formula the AV delay that produces
      the best diastolic resynchronization of left atrial contraction and left
      ventricular ejection can be calculated.Using the above mentioned techniques a
      pragmatic, easy and fast method for increasing CRT performance can be
      established. In cases of worsening heart failure or relevant changes of left
      ventricular dimensions adaptions (re-optimization) of VV and AV delay may be
      needed.

PMID- 18330672
TI  - [New technologies in the optimization of CRT programming].
AB  - After implanting a CRT device, consistent and scheduled patient follow-up is
      mandatory. Besides determining electrode parameters and reviewing arrhythmic
      episodes, these follow-ups focus on monitoring and optimizing congestive heart
      failure therapy. Therefore new CRT devices present methods for heart failure
      surveillance and telemetric transmission of the acquired data, which allows the
      physician to respond immediately to the varying needs of the respective heart
      failure patient. In addition to cardiac resynchronization, optimization of
      atrioventricular (AV) and interventricular (VV) delay provide major hemodynamic
      benefits. As echocardiographic optimization of AV and VV delay is time consuming
      it is often not feasible during daily clinical practice. Therefore implemented
      algorithms that automatically determine and adapt AV and VV delays with respect
      to the fluctuating needs of the patients are essential. This article presents the
      current state of monitoring and optimization methods in CRT devices.

PMID- 18330673
TI  - [His-bundle stimulation and alternative RV stimulation sites].
AB  - The increasing evidence that right ventricular (RV) apical stimulation is
      detrimental for cardiac mechanics and increases the risk of new onset heart
      failure and mortality promotes strategies to avoid ventricular pacing and - if
      not applicable due to atrioventricular block - stipulates the search for
      alternative techniques of pacing the heart from the right ventricle. Despite more
      than 15 years of clinical research it remains unclear whether pacing from the
      right ventricular outflow tract or septum, dual site RV stimulation or selective
      pacing of the His bundle results in hemodynamic and prognostic benefit over the
      traditional method of apical RV pacing. The article reviews pertinent literature
      and tries to demonstrate pathophysiological mechanisms.

PMID- 18330674
TI  - [Biventricular stimulation for AV block].
AB  - Since the establishment of cardiac resynchronization therapy in left bundle
      branch block and mechanical asynchrony, the adverse effects of right ventricular
      apical pacing have gained increasing scientific interest. The sequelae of
      "iatrogenic desynchronization" on cardiac structure and function as well as on
      patients' prognosis could be well documented. "Minimally desynchronizing"
      stimulation strategies could be an alternative for patients needing ventricular
      pacing. The search for hemodynamically more advantageous alternative right
      ventricular pacing sites has failed so far to deliver well validated results, and
      due to the somewhat higher lead dislodgment rates pure left ventricular pacing
      cannot be recommended, at least not in pacemaker-dependent patients. Hence there
      is the question for primary biventricular stimulation in patients with AV block.
      The results of several biventricular studies with limited numbers of patients
      have been promising with respect to structural and functional surrogate
      endpoints. Two major controlled prospective and prognostically orientated
      studies, the BIOPACE study and the BLOCK-HF study, are currently underway and
      will report results in the next few years. According to the actual guidelines of
      the European Society of Cardiology (ESC) the implantation of a biventricular
      system is recommended in patients with AV block even without left bundle branch
      block (Class IIa, evidence level C) if they fulfill the remaining criteria that
      justify the implantation of a biventricular system. According to the guidelines
      for pacemaker therapy of the German Cardiac Society (GCS) biventricular pacing
      can be considered in these patients. Both societies do expressly permit the
      implantation of biventricular systems with ICD backup if indicated.

PMID- 18330676
TI  - Novel synonymous substitution in POMGNT1 promotes exon skipping in a patient with
      congenital muscular dystrophy.
AB  - Walker-Warburg syndrome, muscle-eye-brain disease, Fukuyama congenital muscular
      dystrophy, congenital muscular dystrophy type 1C, and congenital muscular
      dystrophy type 1D are overlapping clinical entities belonging to a subgroup of
      the congenital muscular dystrophies (CMD), collectively designated
      dystroglycanopathies, in which the common underlying defect is hypoglycosylation
      of alfa-dystroglycan. Currently, six different genes are known to be implicated
      in these diseases: POMT1, POMT2, POMGNT1, FCMD, FKRP, and LARGE. We report the
      molecular characterization of a patient presenting clinical features of CMD and
      reduced immunostaining for alfa-dystroglycan in muscle. Three candidate genes
      (FCMD, POMT1 and POMGNT1) were analyzed, and a total of 18 sequence variants were
      detected: 15 polymorphisms in POMT1 [including three unreported single nucleotide
      polymorphisms (SNPs)], two polymorphisms in FCMD, and the exonic silent mutation
      c.636C > T in POMGNT1. Expression analysis revealed that this apparently silent
      mutation compromises correct premessenger RNA (mRNA) splicing, promoting skipping
      of the entire exon 7, with a consequent frameshift. In silico analysis of this
      mutation did not predict alterations in the canonical splice sequences, but
      rather the creation of a new exonic splice silencer. The recognition of such
      disease-causing elements may contribute to the further understanding of RNA
      processing and assist mutation screening in routine diagnosis, where such changes
      may be underestimated. To aid clinical diagnosis, we generated publicly available
      LOVD-powered Locus Specific Databases for these three genes and recorded all
      known sequence variants ( http://www.dmd.nl ).

PMID- 18330678
TI  - Dual-specificity MAP kinase phosphatases (MKPs) and cancer.
AB  - There are ten mitogen-activated protein kinase (MAPK) phosphatases (MKPs) that
      act as negative regulators of MAPK activity in mammalian cells and these can be
      subdivided into three groups. The first comprises DUSP1/MKP-1, DUSP2/PAC1,
      DUSP4/MKP-2 and DUSP5/hVH-3, which are inducible nuclear phosphatases. With the
      exception of DUSP5, these MKPs display a rather broad specificity for
      inactivation of the ERK, p38 and JNK MAP kinases. The second group contains three
      closely related ERK-specific and cytoplasmic MKPs encoded by DUSP6/MKP-3,
      DUSP7/MKP-X and DUSP9/MKP-4. The final group consists of three MKPs DUSP8/hVH-5,
      DUSP10/MKP-5 and DUSP16/MKP-7 all of which preferentially inactivate the stress
      activated p38 and JNK MAP kinases. Abnormal MAPK signalling will have important
      consequences for processes critical to the development and progression of human
      cancer. In addition, MAPK signalling also plays a key role in determining the
      response of tumour cells to conventional cancer therapies. The emerging roles of
      the dual-specificity MKPs in the regulation of MAPK activities in normal tissues
      has highlighted the possible pathophysiological consequences of either loss (or
      gain) of function of these enzymes as part of the oncogenic process. This review
      summarises the current evidence implicating the dual-specificity MKPs in the
      initiation and development of cancer and also on the outcome of treatment.

PMID- 18330677
TI  - Clinical investigation in highly disease-affected rheumatoid arthritis patients
      in Japan with adalimumab applying standard and general evaluation: the CHANGE
      study.
AB  - This multicenter, double-blind study evaluated the effects of three doses of
      adalimumab in Japanese patients with rheumatoid arthritis (RA). Patients were
      randomized to placebo (n = 87) or adalimumab 20 mg (n = 87), 40 mg (n = 91), or
      80 mg (n = 87) every other week for 24 weeks. The primary efficacy endpoint was
      the American College of Rheumatology criteria for 20% improvement (ACR20) at Week
      24. At Week 24, all adalimumab treatment groups achieved statistically
      significantly better ACR20 response rates (20 mg: 28.7%, P < 0.05; 40 mg: 44.0%,
      P < 0.001; and 80 mg: 50.6%, P < 0.001) versus placebo (13.8%), as well as
      statistically significantly greater ACR50 and ACR70 responses for the two higher
      adalimumab doses versus placebo. Rates of adverse events were comparable between
      the adalimumab groups and the placebo group, except for injection-site reactions,
      which occurred in more adalimumab-treated patients. Adalimumab 20, 40, and 80 mg
      were safe and effective in Japanese patients; however, the greatest responses
      occurred with the 40 and 80 mg doses. These results and comparable ACR20
      responses in Western patients support adalimumab 40 mg every other week as the
      appropriate dosage to treat RA in Japanese patients.

PMID- 18330679
TI  - Fluoride incorporation in hydroxyapatite/gelatin nanocomposite.
AB  - The incorporation of fluoride ion into hydroxyapatite (HAp)/gelatin (GEL)
      nanocomposite was investigated. The F(-) ion incorporation into OH(- )site of HAp
      phase was an energetically active process, which could be confirmed from the
      spray solution reaction. The precursors of Ca(2+) in water and phosphates in
      aqueous gelatin were mixed in the humidified air chamber by air spray, and then
      the precipitates were aged in a reactor. The F(-) ion precursor was dissolved in
      the starting solution of Ca(OH)(2) in water, and the resulted Ca(OH, F)(2)
      complex droplets induced the formation of stable fluoroapatite (F, OH)Ap. The
      reaction kinetics could be assumed from TEM morphology with ED, XRD and FT-IR
      analysis.

PMID- 18330680
TI  - The desire to gamble: the influence of outcomes on the priming effects of a
      gambling episode.
AB  - The influence of gambling outcomes on the efficacy of a short gambling episode to
      prime motivation to continue gambling was determined in two experiments in which
      desire to gamble was evaluated while participants played a slot machine located
      in a virtual reality casino. In experiment 1, 38 high-risk [>3 Problem Gambling
      Severity Index (PGSI)] [Ferris and Wynne (The Canadian problem gambling index:
      final report, 2001)] and 36 non-problem gamblers (0 PGSI) either won or lost a
      modest amount. Among high-risk gamblers, winning resulted in a greater increase
      in the desire to continue gambling than did losing. In experiment 2, 39 high
      risk, 33 low-risk (0 < PGSI < 3), and 31 non-problem gamblers experienced either
      a single large win or a series of small wins (equivalent monetary gain).
      Participants were permitted to continue playing as long as they wanted (all
      subsequent spins being losses) thus permitting evaluation of persistence
      (resistance to extinction). Throughout, desire to gamble was assessed using a
      single item measure. High-risk gamblers who experienced a large win reported
      significantly greater desire to gamble upon voluntary cessation than those who
      experienced a series of small wins. It seems that the priming effects of a short
      gambling episode are contingent on the pattern of outcomes experienced by the
      gambler. The data were related to motivational factors associated with gambling,
      gambling persistence, and chasing losses.

PMID- 18330681
TI  - Optimization of Verapamil drug analysis by excitation-emission fluorescence in
      combination with second-order multivariate calibration.
AB  - Excitation emission fluorescence matrices (EEMs) of Verapamil drug were obtained
      by direct and by derivatization fluorescence spectroscopy. The fluorescence
      excitation and emission wavelengths were displaced to longer wavelengths and the
      fluorescence intensity was enhanced upon derivation with respect to the native
      fluorescence of the drug. The complete EEM of the native fluorescence of the drug
      and of the derivatization product were rapidly acquired by using a charged
      coupled device detector (CCD), which is advantageous in terms of speed in the
      analysis, with respect to the use of a conventional photomultiplier detector. The
      EEMs were analyzed by several second-order multivariate calibration methods
      exploiting the second order advantage. The three-dimensional decomposition
      methods used, based in different assumptions about the trilinearity of the three
      way data structure under analysis, were parallel factor analysis (PARAFAC),
      bilinear least squares (BLLS), parallel factor analysis 2 (PARAFAC2) and
      multivariate curve resolution-alternating least squares (MCR-ALS). The
      determination was performed by using the standard addition approach. The figures
      of merit of the PARAFAC and BLLS methods were calculated, obtaining a lower limit
      of detection with the derivatization procedure, when compared with the direct
      measurement of the fluorescence of the drug. In Verapamil drug the best
      estimations were found with the BLLS and the MCR-ALS models. In the
      quantification of Verapamil in a pharmaceutical formulation the best estimation,
      when compared with the result obtained by the US Pharmacopeia high performance
      liquid chromatography approach, was obtained by direct fluorescence spectroscopy
      with MCR-ALS and by derivatization fluorescence spectroscopy with the PARAFAC2
      model.

PMID- 18330682
TI  - Cellular uptake of fluorescent labelled biotin-streptavidin microspheres.
AB  - Amino functionalized, cross-linked, polystyrene microspheres were covalently
      loaded with streptavidin to which was coupled fluorescently labeled biotin and
      biotinylated-tagged DNA. These biotin-streptavidin microsphere conjugates were
      then successfully delivered into cells. The application of the streptavidin
      biotin technology to these microspheres allows the effective delivery of any
      biotinylated material into intact mammalian cells, without the need for delicate
      procedures such as micro-injection.

PMID- 18330683
TI  - Fluorescence quenching of substituted polyperylene with functionalized
      polythiophenes.
AB  - The present investigation focuses the influence of polythiophene i) containing
      hetero aromatic structures and ii) containing mesogenic groups towards the
      photoluminescence properties of substituted polyperylene (PPE). The structural
      contribution towards the optical properties was individually discussed. The
      photoluminescence of PPE was quenched to the maximum level (30%) when it was
      blended with polythiophene with mesogenic groups containing longer alkyl spacer.
      Results of the same blend in solid-state shows 85% of PL quenching.

PMID- 18330684
TI  - Size distribution and molecular associations of plasma fibronectin and
      fibronectin crosslinked by transglutaminase 2.
AB  - Fibronectin (FN) is a ubiquitously expressed cell adhesion protein capable of
      assembling into large, extended fibrillar networks as part of an extracellular
      matrix (ECM) that regulates cell behavior. FN is a substrate for certain members
      of the transglutaminase family of protein-crosslinking enzymes-enzymes which can
      modify the ability of FN to support cell adhesion. In this study, we have
      analyzed the thermo-chemical stability of plasma FN in its noncrosslinked form,
      and after crosslinking by transglutaminase 2 (TG2), using dynamic light
      scattering. We report that FN is found in a generally globular (8.7 nm
      hydrodynamic radius), dimerized form in aqueous solutions, but unfolds into a
      linear arrangement at high ionic (1 M NaCl) and chaotropic (5 M urea)
      environments. FN conformation remained stable after multiple heating and cooling
      cycles ranging from 4 to 60 degrees C. Crosslinking of FN with TG2 formed large,
      multimeric complexes having high chemical stability in aqueous, high ionic and
      chaotropic environments, demonstrating that this covalent modification stabilizes
      FN. Given recent data that substrate (e.g. ECM) rigidity profoundly affects cell
      differentiation and behavior, we further studied how TG2 crosslinking affects the
      molecular rigidity of FN by obtaining atomic force microscopy nanoindentation
      measurements from untreated and crosslinked FN samples embedded in acrylamide
      gels. We demonstrate that TG2-mediated crosslinking of FN significantly increases
      Young's modulus (of elasticity), an observation of increased rigidity having
      important implications with respect to the biological role of ECM protein
      crosslinking in cell signaling and guiding cell differentiation.

PMID- 18330685
TI  - SOCS-1 inhibits TNF-alpha-induced cardiomyocyte apoptosis via ERK1/2 pathway
      activation.
AB  - Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine involved in
      mitogen-activated protein kinase (MAPK) signaling pathways, contributes to the
      pathogenesis of cardiovascular diseases. Recently, suppressor of cytokine
      signaling-1 (SOCS-1) has been shown to modulate responses to TNF-alpha. However,
      whether SOCS-1 suppresses TNF-alpha-dependent apoptotic processes in
      cardiomyocytes and whether MAPK pathways mediate this effect have not been
      clearly elucidated. This study was carried out to define the role of SOCS-1 on
      TNF-alpha-induced apoptosis in neonatal rat cardiomyocytes and to investigate the
      signal pathways involved. Exposure to TNF-alpha (10 ng/ml for 24 h) significantly
      increased the number of apoptotic cells, the activity of caspase-8 and caspase-3,
      and the Bax/Bcl-xl ratio. In contrast, adenovirus-mediated gene transfer of SOCS
      1 reversed the pro-apoptotic effect of TNF-alpha. Additionally, preincubation of
      cardiomyocytes with the extracellular signal-regulated kinase-1 and -2 (ERK1/2)
      inhibitor PD98059 attenuated the protective effect of SOCS-1, but the p38-MAPK
      inhibitor SB203580 and the c-Jun amino-terminal kinase (JNK) inhibitor SP600125
      had no effect. Furthermore, the TNF-alpha-induced decrease in the phosphorylation
      of ERK1/2 was abolished by overexpression of SOCS-1. These findings suggest that
      SOCS-1 prevents TNF-alpha-induced apoptosis in cardiac myocytes via ERK1/2
      pathway activation.

PMID- 18330686
TI  - New concepts in understanding and modulating atrial repolarisation in patients
      with atrial fibrillation.
AB  - Atrial fibrillation is the most frequent cardiac arrhythmia in clinical practice.
      Although much has been learned, the underlying mechanisms are incompletely
      understood. Clinically used antiarrhythmic drugs are limited in their efficacy to
      terminate atrial fibrillation or to maintain sinus rhythm and were associated
      with substantial toxicity including life-threatening ventricular arrhythmias.
      Novel therapeutic approaches suggest targeting of atrium-selective ion channels
      and pathology-specific alterations in atrial repolarisation and arrhythmogenesis
      as promising drug targets for patients with atrial fibrillation. This article
      focuses on novel aspects of altered atrial repolarisation and discusses atrium
      selective (I(Kur), I(K,ACh)) and pathology-specific (I(K,ACh)) ion channels as
      potential targets for safe and effective treatment of atrial fibrillation.

PMID- 18330687
TI  - Common processes in evidence-based adolescent HIV prevention programs.
AB  - Dissemination of evidence-based HIV prevention programs for adolescents will be
      increased if community interventionists are able to distinguish core, essential
      program elements from optional, discretionary ones. We selected five successful
      adolescent HIV prevention programs, used a qualitative coding method to identify
      common processes described in the procedural manuals, and then compared the
      programs. Nineteen common processes were categorized as structural features,
      group management strategies, competence building, and addressing developmental
      challenges of adolescence. All programs shared the same structural features (goal
      setting and session agendas), used an active engagement style of group
      management, and built cognitive competence. Programs varied in attention to
      developmental challenges, emphasis on behavioral and emotional competence, and
      group management methods. This qualitative analysis demonstrated that successful
      HIV programs contain processes not articulated in their developers' theoretical
      models. By moving from the concrete specifics of branded interventions to
      identification of core, common processes, we are consistent with the progress of
      "common factors" research in psychotherapy.

PMID- 18330688
TI  - The development of hyperactive-impulsive behaviors during the preschool years:
      the predictive validity of parental assessments.
AB  - The objectives of this study were to establish the different developmental
      trajectories of hyperactive-impulsive behaviors on the basis of both mother and
      father ratings at 19, 32, 50, and 63 months, and to examine the predictive
      validity of these trajectories with respect to later hyperactive-impulsive
      behaviors, as rated by teachers in the first 2 years of school. Hyperactive
      impulsive behaviors were assessed in a population-based sample of 1,112 twins
      (565 boys and 547 girls) at 19, 32, 50, and 63 months of age. The results
      revealed a differentiated and consistent view of developmental trajectories of
      hyperactive-impulsive behaviors derived from these repeated assessments, with
      7.1% of children seen by mothers (7% for fathers) as displaying high and stable
      hyperactive-impulsive behaviors. According to mother ratings, children on a high
      chronic trajectory were more likely than other children to display hyperactive
      impulsive behaviors at 72 and 84 months according to their teachers. Repeated
      measures over time and father-based trajectories significantly added to the
      prediction teacher later ratings of hyperactive-impulsive behaviors. These
      results support the predictive validity of parental assessment of hyperactive
      impulsive behaviors during the preschool years and their use to identify children
      at risk for further evaluation and possible intervention.

PMID- 18330689
TI  - Post-traumatic reactions in adolescents: how well do the DSM-IV PTSD criteria fit
      the real life experience of trauma exposed youth?
AB  - This study examined the structure and symptom specific patterns of post traumatic
      distress in a sample of 1,581 adolescents who reported exposure to at least one
      traumatic event. Symptom reporting patterns are consistent with past literature
      in that females reported more symptoms than males and older youth reported more
      symptoms than did their younger peers. Young people reporting exposure to
      exclusively violent type traumas were also found to be more likely to endorse
      symptoms than peers exposed exclusively to non violent type traumas. Confirmatory
      factor analysis provided stronger support for a four-factor model of PTSD than
      either the DSM-IV model or an alternate model. Further examination of the four
      factor model revealed gender differences in factor loadings with small to
      moderate effect sizes for recurrent, distressing memories, flashbacks, restricted
      affect, difficulty remember details, detachment, limited future orientation,
      hypervigilance and startle symptoms. Differences in factor loadings with the four
      factor model were also noted between younger and older adolescents, with medium
      to large effect sizes on the arousal items. In contract, comparison of the factor
      loadings revealed only small differences between youth exposed exclusively to
      violent traumatic stressors and those exposed exclusively to non violent
      traumatic stressors, suggesting relative similarity between these two groups.

PMID- 18330690
TI  - Friendships with peers who are low or high in aggression as moderators of the
      link between peer victimization and declines in academic functioning.
AB  - This paper reports two prospective investigations of the role of friendship in
      the relation between peer victimization and grade point averages (GPA). Study 1
      included 199 children (105 boys, 94 girls; mean age of 9.1 years) and Study 2
      included 310 children (151 boys, 159 girls; mean age of 8.5 years). These
      children were followed for two school years. In both projects, we assessed
      aggression, victimization, and friendship with a peer nomination inventory, and
      we obtained children's GPAs from a review of school records. Peer victimization
      was associated with academic declines only when children had either a high number
      of friends who were above the classroom mean on aggression or a low number of
      friends who were below the classroom mean on aggression. These results highlight
      the importance of aggression levels among friends for the academic adjustment of
      victimized children.

PMID- 18330691
TI  - Cloning, expression pattern, chromosomal localization, and evolution analysis of
      Porcine gnaq, gna11, and gna14.
AB  - The Gq class is one subfamily of the G protein alpha subunits multigene family.
      It comprises four genes: Gnaq, Gna11, Gna14, and Gna15. In mice and humans, the
      alpha subunit is an essential component of G protein interaction with receptors
      and effectors. We report here the cloning and characterization of porcine Gnaq,
      Gna11, and Gna14. We have cloned the full-length coding sequences of porcine
      Gnaq, Gna11, and Gna14 (1,080, 1,080, and 1,068 bp, respectively) and then mapped
      them chromosomally to regions 1q21-27, 2q21-24, and 1q21-27 by radiation hybrid
      mapping. Tissue distribution analysis indicated that Gnaq and Gna11 were
      coexpressed in liver, heart, muscle, spleen, adipose tissue, brain, and uterus,
      but Gna14 mRNA was detected only in kidney and lung. The phylogenetic trees
      reveal that porcine Gnaq, Gna11, and Gna14 are evolutionarily closer to their
      human homologs. This is the first report of molecular cloning and
      characterization of porcine Gnaq, Gna11, and Gna14, which will be helpful for
      further understanding of the physiological role of Gq class genes in pigs.

PMID- 18330692
TI  - Researchers, practitioners, and funders: using the framework to get us on the
      same page.
AB  - The worlds of prevention research and practice are largely disconnected. The
      growing body of scientific knowledge regarding effects of prevention programs is
      not often disseminated and translated in a manner that leads to wide scale
      changes in practice. The Centers for Disease Control and Prevention, in
      collaboration with a team of academic researchers, has developed the Interactive
      Systems Framework for Dissemination and Implementation to help us understand the
      roles and interactions of those associated with developing knowledge, those
      associated with using the knowledge in practice settings, and those acting in the
      roles of bridge, support, and broker between the research and practice
      communities. This special issue on the Framework presents a variety of
      theoretical, practical and empirical issues related to this framework and its
      subsystems. This compilation of articles discuss the capacity of the Framework's
      subsystems, provide examples of the generally under-developed prevention support
      system, describe the additional challenges involved in disseminating a change in
      culture, discuss the delicate balance and interaction of fidelity and adaptation,
      present a meta-analysis of the relationships between program implementation and
      program outcomes, and include examples of how the Framework has been used to
      guide action. The present commentary on this special issue provides a critical
      examination of the contributions, implications, and challenges raised by each of
      these articles. It also includes a discussion of how the Framework relates to the
      basic values and practice of community psychology and concludes with some
      suggested future directions and challenges for the continued development and use
      of the Framework.

PMID- 18330693
TI  - The impact of family violence, family functioning, and parental partner dynamics
      on Korean juvenile delinquency.
AB  - The present study was aimed at determining the family factors related to juvenile
      delinquency and identifying the effect of family violence, family functioning,
      parental partner dynamics, and adolescents' personality on delinquent behavior
      among Korean adolescents. A cross-sectional study was performed using an
      anonymous, self-reporting questionnaire. The subjects for this study consisted of
      1,943 Korean adolescents, including 1,236 students and 707 juvenile delinquents,
      using a proportional stratified random sampling method. Compared to student
      adolescents, delinquent adolescents perceived their parents as having a higher
      level of dysfunctional parental partner dynamics, poorer family functioning, and
      a higher level of family violence. Furthermore, delinquent adolescents were more
      likely to report a greater incidence of antisocial personality tendencies, a
      higher level of psychosomatic symptoms and frustration, and higher frequencies of
      delinquent behavior compared to student adolescents. Antisocial personality
      tendency and gender had the largest significant total effects on delinquent
      behavior, followed by family violence, psychosomatic symptoms, family
      functioning, parental partner dynamics and need frustration. On the other hand,
      family functioning and parental partner dynamics had the largest indirect effect
      on delinquent behavior. Gender, antisocial personality tendency, and family
      violence, in that order, had the largest direct effects on delinquent behavior.
      In conclusion, it is apparent from the results of the present study that
      delinquent Korean adolescents perceived and experienced significantly more family
      dysfunction, family violence, and poor parental partner dynamics than did non
      delinquents.

PMID- 18330694
TI  - Increased racial differences on breast cancer care and survival in America:
      historical evidence consistent with a health insurance hypothesis, 1975-2001.
AB  - PURPOSE: This study examined whether race/ethnicity had differential effects on
      breast cancer care and survival across age strata and cohorts within stages of
      disease. METHODS: The Detroit Cancer Registry provided 25,997 breast cancer
      cases. African American and non-Hispanic white, older Medicare-eligible and
      younger non-eligible women were compared. Successive historical cohorts (1975
      1980 and 1990-1995) were, respectively, followed until 1986 and 2001. RESULTS:
      African American disadvantages on survival and treatments increased
      significantly, particularly among younger women who were much more likely to be
      uninsured. Within node positive disease all treatment disadvantages among younger
      African American women disappeared with socioeconomic adjustment. CONCLUSIONS:
      Growth of this racial divide implicates social, rather than biological, forces.
      Its elimination will require high quality health care for all.

PMID- 18330695
TI  - Conservative surgery in patients with multifocal/multicentric breast cancer.
AB  - PURPOSE: Many physicians recommend mastectomy in case of multifocal (MF) or
      multicentric (MC) breast cancer due to a theoretical risk of poor local control
      with less extensive surgery. We retrospectively evaluate outcome of patients with
      MF/MC cancers who had breast conservation with specific attention on local
      control and predictive factors of recurrence. PATIENTS AND METHODS: Four hundred
      and seventy six patients with either MF (n = 421) or MC (n = 55) breast cancer,
      underwent breast-conserving surgery between 1997 and 2002 in a single
      institution. Median follow up was 73 months (range 11-118). RESULTS: Median age
      was 53 years (range 23-86). Invasive lobular carcinoma was found in 88 patients
      (18.5%) and mixed ductal-lobular cancer in 27 (5.7%) patients. Two hundred and
      sixty-seven patients (76.7%) had two identified tumor foci, 55 patients (15.3%)
      had three and 29 patients (8.0%) had four or more. Two hundred and sixty-one
      patients (55.3%) had nodal involvement. The 5-year cumulative incidence of local
      relapse was 5.1%. At the multivariate analysis, over-expression of HER2/neu and
      lack of both estrogen and progesterone receptors (HR: 3.2, 95% C.I. 1.01-10.0,
      and HR: 2.7, 95% C.I. 1.06-7.7, respectively) were associated with a higher
      ipsilateral breast cancer reappearance rate. Involvement of four or more lymph
      nodes and lack of estrogen and progesterone receptors (HR: 2.7, 95% C.I. 1.06
      6.7, and HR: 4.7, 95% C.I. 2.1-10.4, respectively) were associated with poorer
      overall survival. CONCLUSIONS: In selected patients with MF/MC breast cancer,
      wide conservative surgery is not associated with poor local disease control and
      can be considered whenever acceptable cosmetic results can be achieved.

PMID- 18330696
TI  - The influence of overweight and insulin resistance on breast cancer risk and
      tumour stage at diagnosis: a prospective study.
AB  - It is hypothesized that insulin resistance and related metabolic factors may
      influence breast cancer risk, however the epidemiological evidence remains
      inconclusive. We conducted a case-control study nested in a prospective cohort in
      Northern Sweden, to clarify the associations of body mass index (BMI), leptin,
      adiponectin, C-peptide, and glycated haemoglobin (HbA1c) with breast cancer risk.
      We also investigated whether these associations may be modified by age at
      diagnosis, tumour stage, and oestrogen and progesterone receptor status. During
      follow-up, 561 women developed invasive breast cancer and 561 matched controls
      were selected. Conditional logistic regression was used to calculate odds ratios
      (OR) as estimates of relative risk, and 95% confidence intervals (CI). The
      associations of BMI, leptin and HbA1c with breast cancer risk differed
      significantly according to whether the tumour was diagnosed as stage I or stage
      II-IV (P (heterogeneity) all <0.05). These factors were significantly inversely
      associated with risk in the group of stage I tumours, with ORs for top vs. bottom
      tertile for BMI of 0.48 (95% CI, 0.30-0.78, P (trend) = 0.004); leptin, 0.64 (95%
      CI, 0.41-1.00, P (trend) = 0.06); and HbA1c, 0.47 (95% CI, 0.28-0.80, P (trend) =
      0.005). For stage II-IV tumours, there was a suggestion of an increased risk with
      higher levels of these factors. There were no significant differences in the
      associations of BMI, leptin, adiponectin, C-peptide and HbA1c with breast cancer
      risk in subgroups of age at diagnosis or tumour receptor status. This prospective
      study suggests that BMI, leptin and HbA1c influence breast tumour initiation and
      progression.

PMID- 18330697
TI  - Apolipoprotein D predicts adverse outcome in women >or=70 years with operable
      breast cancer.
AB  - Apolipoprotein D (ApoD) is a lipocalin involved in various cellular processes,
      including cytoprotection. We retrospectively evaluated its prognostic impact in
      272 women (median age 63 (range 21-89) years, with operable breast cancer (Stage
      I or IIa) treated according to national guidelines, stratified by age and
      menopausal status, with a median long-term follow-up of 12 years. ApoD, estrogen
      receptor-alpha (ERalpha), and progesterone receptor (PR) positivity were
      determined by quantitative immunohistochemistry in tissue microarrays taken from
      the invasive front of the tumors and in whole tumor sections. ApoD was expressed
      in 50% of the tumors. Diffuse nuclear and cytoplasmic (ApoD(CN)), but not
      granular cytoplasmic ApoD expression in the invasive front was a detrimental
      factor for elderly patients over 70 years of age, (n = 83), but not for younger
      and pre-menopausal patients. ApoD(CN )expression correlated with lymph node
      metastases (P = 0.04). Moreover, a correlation between ApoD(CN )localization and
      age over 70 years was observed (P = 0.03). In the elderly, ApoD(CN) positive
      tumors had both a significantly shorter relapse-free survival (all locations) (P
      = 0.02) and a decreased breast cancer-specific survival (P < 0.0001). Moreover,
      the prognostic importance of ApoD was dose dependent (P = 0.002) Multivariate
      analysis confirmed the prognostic value of ApoD(CN). When the elderly patients
      were stratified by nodal status, ApoD showed prognostic importance only in the
      node positive patients (n = 30) (HR = 9.6; 95% CI = 2.3-40.4). The potential
      relevance of ApoD in this increasingly frequent group of breast cancer patients
      should be further explored.

PMID- 18330698
TI  - Estrogen suppression in premenopausal women following 8 weeks of treatment with
      exemestane and triptorelin versus triptorelin alone.
AB  - INTRODUCTION: Luteinizing hormone-releasing hormone (LHRH) agonists (e.g.,
      triptorelin) reduce ovarian estrogen production in premenopausal women with
      hormone-sensitive breast cancer. Aromatase inhibitors (e.g., exemestane) inhibit
      extraovarian production of estrogen and may further reduce circulating estrogens
      when combined with an LHRH agonist. METHODS: Healthy premenopausal women were
      randomized to receive 3.75 mg triptorelin (T) on days 1 and 29 with 25 mg
      exemestane (EX) or matched placebo once daily for 8 weeks, from day 1 to day 56.
      The primary objective was to evaluate the effect of T +/- EX on estradiol (E(2))
      suppression by comparing the AUC(day 36-57 )for the 2 treatments. Secondary
      objectives included evaluation of estrone (E(1)), luteinizing hormone (LH), and
      follicle-stimulating hormone (FSH) suppression; effects of EX on the T-induced
      gonadotrophin and estrogen flare; pharmacokinetics (PK); and safety. RESULTS:
      Twenty-eight (14 in each arm) were evaluable for efficacy and PK. Mean plasma
      estrogen levels (AUC(day 36-57)) were significantly lower for subjects who
      received T + EX than for subjects who received T alone (20.6 vs. 54.0 pg d/ml [
      62%; P < 0.05], and 38.9 vs. 198.0 pg d/ml [-80%; P < 0.01] for E(2) and E(1),
      respectively). Coadministration of EX did not affect the initial flare or
      subsequent suppression of LH and FSH following the first dose of T, or the PK of
      T. Both treatments were well tolerated. CONCLUSIONS: Coadministration of T and EX
      resulted in greater estrogen suppression than when T was given alone. These
      findings could translate into improved clinical outcomes for premenopausal breast
      cancer patients receiving LHRH agonists.

PMID- 18330699
TI  - Proteomic scale high-sensitivity analyses of GPI membrane anchors.
AB  - Glycosylphosphatidylinositol (GPI) anchored proteins are ubiquitous in eukaryotic
      cells. Earlier analysis methods required large amounts of purified protein to
      elucidate the structure of the GPI. This paper describes methods for analyzing
      GPIs on a 'proteomic' scale. Partially purified proteins may be run on sodium
      dodecyl sulphate polyacrylamide gel electrophoresis and then blotted onto a
      polyvinylidene difluoride (PVDF) membrane. Following identification of the
      protein the piece of PVDF may be subjected to various chemical treatments, which
      are specific for GPI structures. The first method uses gas chromatography-mass
      spectrometry and it enables the presence of a GPI anchor to be confirmed. The
      second method depends on the cleavage of phosphate bonds and permits the
      carbohydrate structure to be elucidated by electrospray or matrix assisted laser
      desorption ionization-time of flight mass spectrometry. The final method
      described uses deamination of the glucosamine residue to release the lipid moiety
      for analysis by mass spectrometry.

PMID- 18330701
TI  - Comparison and analysis of inter-subject variability of simulated magnetic
      activity generated from gastric electrical activity.
AB  - Electrogastrograms (EGGs) produced from gastric electrical activity (GEA) are
      used as a non-invasive method to aid in the assessment of a subject's gastric
      condition. It has been documented that recordings of the magnetic activity
      generated from GEA are more reliable. Typically, with magnetic measurements of
      GEA, only activity perpendicular to the body is recorded. Also, external
      anatomical landmarks are used to position the magnetic recording devices, SQUIDs,
      (Superconducting Quantum Interference Devices) over the stomach with no allowance
      made for body habitus. In the work presented here, GEA and its corresponding
      magnetic activity are simulated. Using these data, we investigate the effects of
      using a standard SQUID location as well as a customized SQUID position and the
      contribution the magnetic component perpendicular to the body makes to the
      magnetic field. We also explore the effects of the stomach wall thickness on the
      resultant magnetic fields. The simulated results show that the thicker the wall,
      the larger the magnitude of the magnetic field holding the same signal patterns.
      We conclude that most of the magnetic activity arising from GEA occurs in a plane
      parallel to the anterior body. We also conclude that using a standard SQUID
      position can be suboptimal.

PMID- 18330702
TI  - Harry L. Goldsmith, Ph.d.

PMID- 18330703
TI  - Micro-scale dynamic simulation of erythrocyte-platelet interaction in blood flow.
AB  - Platelet activation, adhesion, and aggregation on the blood vessel and implants
      result in the formation of mural thrombi. Platelet dynamics in blood flow is
      influenced by the far more numerous erythrocytes (RBCs). This is particularly the
      case in the smaller blood vessels (arterioles) and in constricted regions of
      blood flow (such as in valve leakage and hinge regions) where the dimensions of
      formed elements of blood become comparable with that of the flow geometry. In
      such regions, models to predict platelet motion, activation, aggregation and
      adhesion must account for platelet-RBC interactions. This paper studies platelet
      RBC interactions in shear flows by performing simulations of micro-scale dynamics
      using a computational fluid dynamics (CFD) model. A level-set sharp-interface
      immersed boundary method is employed in the computations in which RBC and
      platelet boundaries are tracked on a two-dimensional Cartesian grid. The RBCs are
      assumed to have an elliptical shape and to deform elastically under fluid forces
      while the platelets are assumed to behave as rigid particles of circular shape.
      Forces and torques between colliding blood cells are modeled using an extension
      of the soft-sphere model for elliptical particles. RBCs and platelets are
      transported under the forces and torques induced by fluid flow and cell-cell and
      cell-platelet collisions. The simulations show that platelet migration toward the
      wall is enhanced with increasing hematocrit, in agreement with past experimental
      observations. This margination is seen to occur due to hydrodynamic forces rather
      than collisional forces or volumetric exclusion effects. The effect of fluid
      shear forces on the platelets increases exponentially as a function of hematocrit
      for the range of parameters covered in this study. The micro-scale analysis can
      be potentially employed to obtain a deterministic relationship between fluid
      forces and platelet activation and aggregation in blood flow past cardiovascular
      implants.

PMID- 18330704
TI  - Viscoelastic characteristics of in vitro vital and devitalized rat aorta and
      human arterial prostheses.
AB  - The arterial wall viscoelasticity plays an essential role in the vascular
      responsiveness to vasoactive drugs or pathologies. The aim of this investigation
      was to derive and compare resonance curve (RC), natural frequency (f(0)), dynamic
      modulus of elasticity (E'), and coefficient of viscosity (beta) of (i) vital and
      devitalized preparations of rat thoracic and abdominal aorta, (ii) human arterial
      prostheses, and to study the histomorphology of vital and devitalized rat aorta.
      The method of low frequency forced oscillations was employed. RC of vital
      preparations showed a hardening type of elasticity whereas in devitalized
      preparations it was of softening type. E' increased nonlinearly, f(0) decreased
      and beta increased linearly with equivalent intraluminal pressure (p(eqi)).
      Distensibility of abdominal aorta was lower than thoracic aorta. Distensibility
      decreased with increasing p(eqi). E', f(0), and beta increased significantly
      after devitalization. It was suggested that postmortem viscoelastic
      characteristics should not be used directly to specify the vital arteries
      viscoelasticity. RC of human prostheses showed a softening type of elasticity.
      Arterial prostheses have low circumferential distensibility with E'-values higher
      than reported in the literature for human arteries. The method of forced
      oscillations could be employed for studying the arterial wall biomechanics and
      viscoelasticity of arterial prostheses.

PMID- 18330705
TI  - Physiogenomic analysis of localized FMRI brain activity in schizophrenia.
AB  - The search for genetic factors associated with disease is complicated by the
      complexity of the biological pathways linking genotype and phenotype. This
      analytical complexity is particularly concerning in diseases historically lacking
      reliable diagnostic biological markers, such as schizophrenia and other mental
      disorders. We investigate the use of functional magnetic resonance imaging (fMRI)
      as an intermediate phenotype (endophenotype) to identify physiogenomic
      associations to schizophrenia. We screened 99 subjects, 30 subjects diagnosed
      with schizophrenia, 13 unaffected relatives of schizophrenia patients, and 56
      unrelated controls, for gene polymorphisms associated with fMRI activation
      patterns at two locations in temporal and frontal lobes previously implied in
      schizophrenia. A total of 22 single nucleotide polymorphisms (SNPs) in 15 genes
      from the dopamine and serotonin neurotransmission pathways were genotyped in all
      subjects. We identified three SNPs in genes that are significantly associated
      with fMRI activity. SNPs of the dopamine beta-hydroxylase (DBH) gene and of the
      dopamine receptor D4 (DRD4) were associated with activity in the temporal and
      frontal lobes, respectively. One SNP of serotonin-3A receptor (HTR3A) was
      associated with temporal lobe activity. The results of this study support the
      physiogenomic analysis of neuroimaging data to discover associations between
      genotype and disease-related phenotypes.

PMID- 18330706
TI  - What do second language listeners know about spoken words? Effects of experience
      and attention in spoken word processing.
AB  - With a goal of investigating psycholinguistic bases of spoken word processing in
      a second language (L2), this study examined L2 learners' sensitivity to
      phonological information in spoken L2 words as a function of their L2 experience
      and attentional demands of a learning task. Fifty-two Chinese learners of English
      who differed in amount of L2 experience (longer vs. shorter residence in L2
      environment) were tested in an auditory word priming experiment on well-known L2
      words under two processing orientation conditions (semantic, control). Results
      revealed that, with more L2 experience, learners become more sensitive to
      phonological detail in spoken L2 words but that attention to word meaning might
      eliminate this sensitivity, even for learners with more L2 experience.

PMID- 18330707
TI  - Mitochondrial localization and pro-apoptotic effects of the interferon-inducible
      protein ISG12a.
AB  - ISG12a is one of the most highly induced genes following treatment of cells with
      type I interferons (IFNs). The encoded protein belongs to a family of poorly
      characterized, low molecular weight IFN-inducible proteins that includes 6-16
      (G1P3), 1-8U (IFITM3), and 1-8D (IFITM2). Our studies demonstrate that the ISG12a
      protein associates with or inserts into the mitochondrial membrane. Transient
      expression of ISG12a led to decreased viable cell numbers and enhanced
      sensitivity to DNA-damage induced apoptosis, effects that were blocked by Bcl-2
      co-expression or treatment with a pan-caspase inhibitor. ISG12a enhanced
      etoposide induced cytochrome c release, Bax activation and loss of mitochondrial
      membrane potential. siRNA-mediated inhibition of ectopic ISG12a protein
      expression prevented the sensitization to etoposide-induced apoptosis and also
      decreased the ability of IFN-beta pretreatment to sensitize cells to etoposide,
      thereby demonstrating a role for ISG12a in this process. These data suggest that
      ISG12a contributes to IFN-dependent perturbation of normal mitochondrial
      function, thus adding ISG12a to a growing list of IFN-induced proteins that
      impact cellular apoptosis.

PMID- 18330708
TI  - Identification and education of adolescents with asthma in an urban school
      district: results from a large-scale asthma intervention.
AB  - Asthma is a leading cause of hospitalizations, acute care utilization, health
      care costs, and school absences in children. Asthma morbidity is
      disproportionately high in inner city populations. In general, community-based
      public health interventions to reduce asthma morbidity have had modest success
      due in part to their limited reach and low participation by the targeted
      population. Adolescents have been especially difficult to reach. A coalition of
      community organizations developed a school-based, population-level system to
      identify, prioritize, and provide interventions for middle school children with
      asthma in a large urban school district in Oakland, CA. Nearly 92% (n = 8,326) of
      students in the targeted schools took an asthma case identification survey. Of
      those students who took the survey, 17.5% (n = 1,458) had active asthma and were
      eligible for services. Among those identified with active asthma, 83% (n = 1,217)
      voluntarily attended asthma self-management classes at school. The 4-week
      curriculum previously has been shown to significantly improve several indicators
      of asthma control in this population. Retention was high-72% of students who
      enrolled attended at least three of the four curriculum sessions. Many higher
      risk students were subsequently referred to and enrolled in off-site asthma
      services. Large school districts with incomplete or inadequate health records,
      high asthma prevalence, and internal or external services available for students
      with asthma may benefit from a similar model. A system such as the one described
      may be an effective public health strategy for school districts, health
      departments, and community coalitions addressing asthma or other conditions with
      high childhood prevalence.

PMID- 18330709
TI  - League tables, love them or hate them.

PMID- 18330710
TI  - Identification of early senescence-associated genes in rice flag leaves.
AB  - Leaf senescence is one of the key stages of plant leaf development. It is a
      highly complex but ordered process involving expression of large scale senescence
      associated genes, and its molecular mechanisms still remain unclear. By using
      suppression subtractive hybridization, 815 ESTs that are up-regulated at the
      onset of rice flag leaf senescence have been isolated. A total of 533 unigenes
      have been confirmed by macroarray detection and sequencing. 183 of these unigenes
      have GO annotations, involved in macromolecule metabolism, protein biosynthesis
      regulation, energy metabolism, gene expression regulations, detoxification,
      pathogenicity and stress, cytoskeleton organization and flower development.
      Another 121 unigenes co-localized with previously reported known stay-green QTLS.
      RT-PCR analysis on the other novel genes indicated that they can be up-regulated
      in natural early senescence and induced by hormone. Our results indicate that
      senescence is closely related to various metabolic pathways, thus providing new
      insight into the onset of leaf senescence mechanism.

PMID- 18330711
TI  - Mapping of the chromosome 17 BMD QTL in the F(2) male mice of MRL/MpJ x SJL/J.
AB  - Developing treatment strategies for osteoporosis would be facilitated by
      identifying genes regulating bone mineral density (BMD). One way to do so is
      through quantitative trait locus (QTL) mapping. However, there are sex
      differences in terms of the presence/absence and locations of BMD QTLs. In a
      previous study, our group identified a BMD QTL on chromosome 17 in the F(2)
      female mice of the MRL/MpJ x SJL/J cross. Here, we determined whether it was also
      present in the male mice of the same cross. Furthermore, we also intended to
      reduce the QTL region by increasing marker density. Interval mapping showed that
      the same QTL based on chromosomal positions was present in the male mice, with
      logarithmic odds (LOD) scores of 4.0 for femur BMD and 5.2 for total body BMD.
      Although there was a body weight QTL at the same location, the BMD QTL was not
      affected by the adjustment for body weight. Mapping with increased marker density
      indicated a most likely region of 35-55 Mb for this QTL. There were also co
      localized QTLs for femur length, femur periosteal circumference (PC) and total
      body bone area, suggesting possibility of pleiotropy. Runx2 and VEGFA are strong
      candidate genes located within this QTL region.

PMID- 18330712
TI  - Classical and molecular cytogenetic characterization of Agonostomus monticola, a
      primitive species of Mugilidae (Mugiliformes).
AB  - This study reports the first description of the karyotype of Agonostomus
      monticola, a species belonging to a genus which is considered to be the most
      primitive among living mugilid fish. Specimens from Panama and Venezuela were
      cytogenetically analysed by conventional chromosome banding (Ag and base-specific
      fluorochrome staining, C-banding) and by fluorescent in situ hybridization
      (FISH). Agonostomus monticola showed a chromosome complement of 2n = 48, composed
      of 23 acrocentric and one subtelocentric chromosome pairs and a pericentromeric
      distribution of the C-positive heterochromatin in all chromosomes. Major
      ribosomal genes were found to be located on the short arms of the subtelocentric
      chromosome pair number 24 and minor ribosomal genes in a paracentromeric position
      of a single medium-sized chromosome pair. All these observed cytogenetic features
      are similar to those previously described in four representatives of two genera,
      Liza and Chelon, which are considered to be among the most advanced in the
      family. Thus, this karyotypic form might represent the plesiomorphic condition
      for the mullets. This hypothesis regarding the plesiomorphic condition, if
      confirmed, would shed new light on the previously inferred cytotaxonomic
      relationships for the studied species of Mugilidae, because the karyotype with 48
      acrocentric chromosomes, which has been so far regarded as primitive for the
      family, would have to be considered as derived.

PMID- 18330713
TI  - Effects of ethanol on pancreatic beta-cell death: interaction with glucose and
      fatty acids.
AB  - Western lifestyle plays an important role in the prevalence of type 2 diabetes by
      causing insulin resistance and pancreatic beta-cell dysfunction, a prerequisite
      for the development of diabetes. High fat diet and alcohol are major components
      of the western diet. The aim of the present study was to investigate the effects
      of ethanol and fatty acids on beta-cell survival and metabolism. We treated the
      rat beta-cell line RINm5F with ethanol, a mixture of palmitic and oleic acids, or
      both. Reactive oxygen species (ROS) were determined by (5-(and-6)-chloromethyl
      2',7'-dichlorodihydrofluorescein diacetate) (CM-H2DCFDA) fluorescence assay, and
      mitochondrial activity was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl
      tetrazolium bromide (MTT) reduction assay and by determining ATP production. Cell
      viability was assessed with a cell counter and trypan blue exclusion, and the
      mode of cell death by Hoechst33342 and propidium iodide staining. With both
      ethanol and fatty acid treatments, MTT reduction and ATP production decreased,
      whereas ROS production increased. Ethanol treatment had no effect on cell number,
      whereas fatty acid treatment reduced the cell number. Cell incubation with
      ethanol, fatty acids, or both increased the number of Hoechst 33342-positive
      nuclei. However, the majority of nuclei from fatty acid-treated cells were
      stained with propidium iodide, indicating a loss of plasma membrane integrity. We
      conclude that both ethanol and fatty acids generate cellular oxidative stress,
      and affect mitochondrial function in RINm5F beta-cells. However, ethanol causes
      beta-cell death by apoptosis, whereas fatty acids cause cell death predominantly
      by necrosis. It is not known whether these results are applicable to human beta
      cells.

PMID- 18330714
TI  - Anti-angiogenic activity of sesterterpenes; natural product inhibitors of FGF-2
      induced angiogenesis.
AB  - Angiogenesis, the growth of new blood vessels from the pre-existing vasculature
      is of physiological and pathological importance. We have investigated the anti
      angiogenic potential of two naturally occurring sesterterpenes,
      leucosesterterpenone (compound 1) and leucosterlactone (compound 2) isolated from
      the Himalayan plant Leucosceptrum canum and identified as having biological
      activity in preliminary screening. Compound 1 inhibited fibroblast growth factor
      2-induced proliferation, migration in a wounding assay, chemotaxis and tube
      formation with small vessel (human dermal) and large vessel (bovine aortic)
      endothelial cells while compound 2 was largely inactive. Both compounds were also
      active in an in vivo angiogenic model using the chick chorioallantoic membrane.
      Neither compounds showed inhibitory activity in the absence of fibroblast growth
      factor-2. We were able to demonstrate in a binding assay that compounds 1 and 2
      bound to the fibroblast growth factor-2 receptor-1 with IC(50) values of 1.4 +/-
      0.956 and 132.47 +/- 7.90 muM, respectively, with a concomitant down regulation
      of phosphorylated ERK1/2 but did not bind to receptor-2. Compound 1 was less
      hydrophobic than compound 2 and this may contribute to its increased activity.
      Compound 1 is a new addition to the small number of inhibitors of fibroblast
      growth factor-2-induced angiogenesis. The compound was a specific inhibitor in
      that it had no effect on vascular endothelial growth factor or epithelial growth
      factor-induced angiogenesis. Since angiogenesis is essential for tumour
      development we conclude that these compounds may have potential as anti-tumour
      agents.

PMID- 18330715
TI  - Seasonal variations of air pollutant concentrations within Krasnoyarsk City.
AB  - This paper examines the significant differences in seasonal variations of
      criteria pollutant concentrations in various parts of a large urban area. These
      differences are caused by the microclimatic heterogeneity of the city and show
      the influence of breeze and orographic-type circulations on urban air pollution.
      The temperature heterogeneity of Krasnoyarsk territory during the winter leads to
      an increase of 150% in CO air pollution levels in the central part of city.
      During the summer the orographical heterogeneity of Krasnoyarsk City leads to
      increases of up to 400% in air pollution for different areas.

PMID- 18330716
TI  - Distribution of vehicular pollutants in street canyons of Varanasi, India: a
      different case.
AB  - In present study horizontal and vertical distribution of traffic-related
      pollutants (CO and SO(2)) within the street canyons in (CO and SO(2)) Varanasi,
      India was monitored. The results showed that average horizontal profiles of
      traffic-related pollutant concentrations within street canyon at leeward side
      were approximately same as that of windward side. However, the vertical
      concentration of both the pollutants decreases with height above the ground and
      study indicated that CO and SO(2) concentrations at different heights below the
      roof showed clear vertical self-gradient. CO and SO(2) concentration decreased
      with height and the minimum value occurred at the roof. It was concluded from the
      observed results that pollutants from vehicular exhaust emissions in the street
      canyon of Varanasi were evenly distributed. This result may be due to the fact
      that wind vortices are not formed. Therefore, urban planners can use this type of
      streets so that there is proper ventilation and dispersal of pollutants.

PMID- 18330717
TI  - Proteasome activities in the rectus abdominis muscle of young and older
      individuals.
AB  - Sarcopenia is one of the most striking effects of age, the causes and the
      pathogenic mechanisms being largely unknown. Unfortunately, there is limited
      information on the effect of aging on muscle protein breakdown in basal
      conditions. The present study aimed at investigating if skeletal muscle ubiquitn
      mRNA levels and proteasome activities vary with age in healthy individuals. Ub
      mRNA levels were measured by northern blot analysis whereas proteasome activities
      were determined by evaluating the cleavage of specific fluorogenic substrates in
      the rectus abdominis muscle of 14 healthy male individuals. Patients were divided
      in three groups according to the age: (1) 20-30 years (N = 3); (2) 31-64 years (N
      = 5); (3) > or = 65 years (N = 6). Quantitation of the ubiquitin mRNA levels
      (expressed in arbitrary units) (mean (SD) showed no differences among the three
      groups of age (20-30 years: 1352 +/- 441; 31-64 years: 1324 +/- 439; > or = 65
      years: 884 +/- 400; P = 0.33). The correlation between age and muscle ubiquitin
      mRNA levels was not statistically significant (r = -0.4, P = 0.26). The three
      proteasome activities, chymotrypsin-like (CTL), trypsin-like (TL) and peptidyl
      gutamyl-peptidase (PGP), expressed as nkatal x 10(-3)/mg protein, were similar in
      the three groups of patients stratified according to the age. There was no
      correlation between age with either CTL (r = 0.22, P = 0.4), PGP (r = 0.002, P =
      0.9), and TL (r = 0.28, P = 0.33) activities. In conclusion, the present study
      shows that the skeletal muscle proteasome activities do not differ with age in
      healthy male individuals.

PMID- 18330718
TI  - Genetic analysis of hereditary multiple exostoses in Tunisian families: a novel
      frame-shift mutation in the EXT1 gene.
AB  - Hereditary multiple exostoses (HME) is an autosomal dominant orthopaedic disorder
      most frequently caused by mutations in the EXT1 gene. The aim of the present
      study is to determine the underlying molecular defect of HME in two
      multigenerational Tunisian families with 21 affected members and to examine the
      degree of intrafamilial variability. Linkage analysis was performed using three
      microsatellite markers encompassing the EXT1 locus and mutation screening was
      carried out by direct sequencing. In family 1, evidence for linkage to EXT1 was
      obtained on the basis of a maximum LOD score of 4.26 at theta = 0.00 with D8S1694
      marker. Sequencing of the EXT1 revealed a heterozygous G > T transversion
      (c.1019G>T) in exon 2, leading to a missense mutation at the codon 340
      (p.Arg340Leu). In family 2 we identified a novel heterozygous 1 bp deletion in
      the exon 1 (c.529_531delA) leading to a premature codon stop and truncated EXT1
      protein expression (p.Lys177LysfsX15). This mutation was associated with the
      evidence of an intrafamilial clinical variability and considered to be a novel
      disease-causing mutation in the EXT1 gene. These findings provide additional
      support for the involvement of EXT1 gene in the HME disease.

PMID- 18330719
TI  - Concordant correlation of LIV-1 and E-cadherin expression in human breast cancer
      cell MCF-7.
AB  - The recent report highlighted a significant association between signal transducer
      and activator of transcription 3 (STAT3) and Snail and LIV-1 (SLC39A6 or ZIP6),
      the breast cancer-associated protein that belongs to a new subfamily of zinc
      transporters. LIV-1 is a downstream target of STAT3, both in zebrafish and
      mammalian cells and provides control over epithelial-mesenchymal transition
      (EMT). Crucially, these observations link LIV-1, previously demonstrated to be
      associated with lymph node metastasis in breast cancer, to genes with a proven
      role in development. A putative role of LIV-1 as a regulator of E-cadherin that
      modulates the cell-cell adhesion is thus inferred. In present study, the
      correlation of LIV-1 and E-cadherin expression in human breast cancer cell MCF-7
      and the effect of LIV-1 expression on the cell growth were assessed to explore
      the possible mechanisms associated with this observation in breast cancer. It was
      shown that the silencing of LIV-1 would induce the down-expression of E-cadherin.
      There was opposite results if the cells were overexpressed with LIV-1. In
      addition, the results showed that promotion effect after silencing of LIV-1 and
      inhibition effect after overexpression of LIV-1 in transfected cells. To our
      knowledge, this is the first evidence that the expression of E-cadherin could be
      regulated by the zinc transporter LIV-1. The results suggest that there is an
      association of LIV-1 expression with less aggressive tumors due to high E
      cadherin expression because of high LIV-1 expression. LIV-1 may be a regulator of
      E-cadherin.

PMID- 18330720
TI  - The principle of double effect as a guide for medical decision-making.
AB  - Many medical interventions have both negative and positive effects. When health
      care professionals cannot achieve a particular desired good result without
      bringing about some bad effects also they often rely on double-effect reasoning
      to justify their decisions. The principle of double effect is therefore an
      important guide for ethical decision-making in medicine. At the same time,
      however, it is a very controversial tool for resolving complex ethical problems
      that has been criticized by many authors. For these reasons, I examine in this
      paper whether the principle of double effect can serve as a basis for ethical
      decisions in medicine. The conclusion reached in this article is that even though
      this principle has desirable effects on clinical conduct, it is only an
      unreliable guide and physicians and nurses cannot feel secure in continuing to
      use this principle for ethical guidance.

PMID- 18330721
TI  - Caspases activation in hyperthermia-induced stimulation of TRAIL apoptosis.
AB  - In leukemia cells, hyperthermia enhances tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced apoptosis. The phenomenon is caspase-dependent
      and results in membrane changes leading to an increased recognition of TRAIL
      death receptors by TRAIL. Because either caspase-2 or an apical proteolytic event
      has been recently proposed to act as an initiator of the cell death mechanism
      induced by heat shock, we have investigated the hierarchy of caspase activation
      in cells exposed to the combined heat shock plus TRAIL treatment. We report here
      that caspases-2, -3, and -8 were the first caspases to be activated. As expected,
      caspase-8 is required and indispensable during the initiation of this death
      signaling. Caspase-2 may also participate in the phenomenon but, in contrast to
      caspase-8, its presence appears dispensable because its depletion by small
      interfering RNA is devoid of effects. Our observations also suggest a role of
      caspase-3 and of a particular cleaved form of this caspase during the early
      signals of heat shock plus TRAIL-induced apoptosis.

PMID- 18330722
TI  - Anaplastic thyroid carcinoma with rhabdomyoblastic differentiation: a case report
      with a good clinical outcome.
AB  - Anaplastic thyroid carcinoma is a rare and highly malignant disease. Usually,
      this type of tumor is irresectable, and almost all patients die within 1 year
      after diagnosis. We present a case of anaplastic thyroid carcinoma with
      rhabdomyoblastic differentiation and good therapeutic outcome. A 76-year-old
      female was referred to our hospital with a growing, painless neck mass which
      existed for 3 months. Biopsy of the mass showed microscopically and
      immunohistochemically a follicular (Hurthle cell) carcinoma of the thyroid,
      dedifferentiated to an anaplastic carcinoma with divergent differentiation along
      rhabdomyoblastic cell lines. The patient underwent a total thyroidectomy with
      additional lymph node dissection, followed by two episodes of 150 mC I(131)
      therapy and external radiotherapy. After a follow-up of 3 years, the patient
      still remains in a good condition without any signs of recurrent disease. Other
      cases of rhabdomyoblastic and rhabdoid anaplastic thyroid carcinomas have been
      described. Both types of carcinoma are associated with an aggressive clinical
      course. In our case, the patient is still alive without evidence of disease 3
      years after primary therapy. The good clinical outcome of our patient suggests
      that surgical resection, radiotherapy, and I-131 ablation therapy with curative
      intent seems to be an adequate treatment option in patients with anaplastic
      thyroid carcinoma with rhabdoid and rhabdomyoblastic differentiation.

PMID- 18330723
TI  - Choroidal mass as an initial presentation of lung cancer.
AB  - Choroidal mass may be a presenting sign of systemic malignancy. The diagnosis of
      metastatic ocular tumor is important because it can indicate poor prognosis. We
      report a case of a 45-year-old man presenting to our clinic with the complaint of
      decreased vision in the left eye, which is the initial finding of non-small cell
      lung-carcinoma.

PMID- 18330724
TI  - Approach to the patient with recurrent infections.
AB  - Children with a history of recurrent or unusual infections present a diagnostic
      challenge. Differentiation between frequent infections caused by common risk
      factors, versus primary immune dysfunction should be based on a detailed history
      and physical examination and, if indicated, followed by appropriate laboratory
      studies. A high index of suspicion could lead to an early diagnosis and treatment
      of an underlying immune deficiency disease. This article presents to physicians
      an approach to the evaluation of children with recurrent infections. Important
      details from the history and physical examination, and an appropriate choice of
      screening laboratory test to be ordered in a given situation are discussed.

PMID- 18330725
TI  - Immune deficiency disorders with autoimmunity and abnormalities in immune
      regulation-monogenic autoimmune diseases.
AB  - Autoimmunity is frequently observed in patients with primary immune deficiency
      disorders. Monogenic autoimmune diseases include a group of disorders with
      characteristic autoimmunity and immune deficiency for which single gene defects
      have been identified. Currently recognized monogenic autoimmune diseases include
      autoimmune polyendocrinopathy candidiasis and ectodermal dystrophy,
      immunodysregulation polyendocrinopathy enteropathy and X-linked inheritance
      syndrome, autoimmune lymphoproliferative syndrome, and interleukin-2 receptor
      alpha-chain deficiency. These diseases offer important insights into the
      mechanisms of central and peripheral immune tolerance and the pathogenesis of
      defects in these mechanisms.

PMID- 18330727
TI  - Host factors in amniotic fluid and breast milk that contribute to gut maturation.
AB  - The gut represents a complex organ system with regional differences, which
      reflect selective digestive and absorptive functions that change constantly in
      response to bodily requirements and the outside milieu. As a barrier to the
      external environment, gut epithelium must be renewed rapidly and repeatedly.
      Growth and renewal of gut epithelial cells is dependent on controlled cell
      stimulation and proliferation by a number of signaling processes and agents,
      including gut peptides-both endogenous and exogenous sources. This cascade of
      events begins during fetal development; with the ingestion of amniotic fluid,
      this process is enhanced and continued during infancy and early childhood through
      the ingestion of human milk. Events influenced by amniotic fluid during fetal
      development and those influenced by human milk that unfold after birth and early
      childhood to render the gut mature are presented.

PMID- 18330726
TI  - Inflammatory mediators in the immunobiology of bronchopulmonary dysplasia.
AB  - Inflammation is important in the development of bronchopulmonary dysplasia (BPD).
      Polymorphonuclear cells and macrophages and proinflammatory cytokines/chemokines
      denote early inflammation in clinical scenarios such as in utero inflammation
      with chorioamnionitis or initial lung injury associated with respiratory distress
      syndrome or ventilator-induced lung injury. The persistence and non-resolution of
      lung inflammation contributes greatly to BPD, including altering the lung's
      ability to repair, contributing to fibrosis, and inhibiting secondary septation,
      alveolarization, and normal vascular development. Further understanding of the
      role of inflammation in the pathogenesis of BPD, in particular, during the
      chronic inflammatory period, offers us the opportunity to develop inflammation
      related prevention and treatment strategies of this disease that has long
      standing consequences for very premature infants.

PMID- 18330728
TI  - Exercise-induced bronchospasm in children.
AB  - This review will encompass definition, history, epidemiology, pathogenesis,
      diagnosis, and management of exercise -induced bronchospasm in the pediatric
      individual with and without known asthma. Exercise induced asthma is the
      conventional term for transient airway narrowing in a known asthma in association
      with strenuous exercise usually lasting 5-10 minutes with a decline in pulmonary
      function by at least 10%. Exercise induced asthma will be referred to as exercise
      induced bronchospasm in an asthmatic. Exercise-induced bronchospasm (EIB ) is the
      same phenomenon in an individual without known asthma. EIB can be seen in healthy
      individuals including children as well as defense recruits and competitive or
      elite athletes. The diagnosis with objective exercise challenge methods in
      conjunction with history is delineated. Management is characterized with
      pharmacotherapy and non pharmacotherapeutic measures for underlying asthma as
      well as exercise induced bronchospasm and inhalant allergy. Children can
      successfully participate in all sports if asthma is properly managed.

PMID- 18330729
TI  - Pediatric angioedema.
AB  - Angioedema is a self-limited nonpitting edema generally affecting the deeper
      layers of the skin and mucous membranes. It is the result of increased vascular
      permeability causing the leakage of fluid into the skin in response to potent
      vasodilators released by immunologic mediators. Two main pathways are thought to
      be implicated in angioedema. The mast cell pathway in which preformed mediators,
      such as histamine, rapidly formed mediators, leukotrienes and prostaglandins, are
      released from mast cells through IgE or direct activation. This is the most
      common pathway among children, with food, medications, and infections commonly
      implicated. The second pathway is the kinin pathway, most notably affected by
      angiotensin-converting enzyme (ACE) inhibitors and hereditary forms of
      angioedema, which ultimately results in the formation of bradykinin, a potent
      vasodilator. Angioedema is being encountered with increasing frequency,
      particularly among children and is important to recognize and treat for its life
      threatening associated manifestations such as anaphylaxis and airway obstruction.
      Although angioedema is still not fully understood, we have broadened our
      understanding of the possible causes and clinical course of angioedema. An
      understanding of these potential causes and mechanisms by which angioedema can
      occur may guide the clinician in determining the need for diagnostic testing and
      the extent of treatment.

PMID- 18330730
TI  - A review of non-cystic fibrosis pediatric bronchiectasis.
AB  - With the implementation of vaccination programs and the use of antibiotics,
      developed countries have seen a decline in infection-related pediatric
      bronchiectasis. However, significant morbidity from bronchiectasis is still seen
      and both infectious and noninfectious causes of bronchiectasis in the pediatric
      population remain. A review of the literature will be presented including causes
      of pediatric bronchiectasis, clinical symptoms and signs, laboratory evaluation
      and imaging, as well as treatment options. This review stresses the importance of
      early evaluation and treatment in children with recurrent cough, sinusitis,
      potential foreign-body aspiration, or gastroesophageal reflux to prevent the
      complications of ongoing respiratory disease and bronchiectasis.

PMID- 18330731
TI  - Interdisciplinary tumour boards in Switzerland: quo vadis?
AB  - BACKGROUND/AIMS: The objective of the present investigation is twofold: first, to
      assess how interdisciplinary tumour boards in Switzerland are designed,
      established, and rated in clinical practice; and second, to evaluate perceptions
      regarding the determination of cancer centres as required by the Swiss National
      Cancer Programme. METHODS: An anonymous questionnaire was sent to the heads of
      surgical departments in Switzerland (n = 110). Among the clinics contacted were
      11 large referral centres (type A clinics), 48 surgical departments of cantonal
      hospitals (type B clinics), and 51 regional surgical departments (type C
      clinics). RESULTS: For most type A and B clinics, tumour boards are held on a
      weekly basis (A: 100%, B: 88%, C: 26%). On average, 66% of respondents (A: 90%,
      B: 71 %, C: 52 %) consider tumour boards a standard of care for every cancer
      patient. Determination of cancer centres was favoured by 49% of all respondents
      (A: 80%, B: 56%, C: 32 %). CONCLUSION: The present survey in Switzerland clearly
      shows significant differences between type A, B, and C clinics in the use of
      tumour boards and in their perception as a standard of care. There are wide
      discrepancies in the perceived need to determine cancer centres in Switzerland as
      required by the Swiss National Cancer Programme. Since the implementation of
      tumour boards is associated with optimised cancer patient care, continuing
      education on their importance is a vital necessity.

PMID- 18330732
TI  - Acute kidney injury in an infectious disease intensive care unit - an assessment
      of prognostic factors.
AB  - BACKGROUND: Acute kidney injury (AKI) is a common complication in many infectious
      diseases. There are few studies to investigate risk factors for death in
      infectious diseases-associated AKI. METHODS: This is a retrospective study
      including all patients with acute kidney injury (AKI) admitted to an infectious
      diseases intensive care unit (ICU) in Brazil between October 2003 and September
      2006. RESULTS: A total of 722 patients were admitted to the infectious disease
      ICU in the study period. AKI occurred in 147 cases (17.7%). The mean age was 45
      +/- 5.6 years, and 77% were male. The mean length of hospital stay was 11.5 +/-
      10.3 days. The main causes of ICU hospitalization were acquired immunodeficiency
      syndrome (AIDS)-related diseases (28 .6%), pneumonia 13%), leptospirosis (11.6%),
      meningitis (8.2%), disseminated histoplasmosis (6.8%) and tetanus (5.4%). The
      main cause of AKI was sepsis (41.5%). Patients were classified according to RIFLE
      as "Risk" (5.6%), "Injury" (21.7%) and "Failure" (72.7%). Patients in "Failure"
      showed a higher mortality (p = 0.007). Multivariate analysis showed that
      dependent risk factors for death were oliguria (OR = 5.59, P = 0.002), metabolic
      acidosis (OR = 5.13, P = 0.01), sepsis (OR = 4.79, P = 0.001), hypovolaemia (OR =
      4.11, P = 0.01), use of vasoactive drugs (OR = 3.34, P = 0.02), use of mechanical
      ventilation (OR = 2.94, P = 0.03) and high APACHE II score (OR = 1.14, P =
      0.001). CONCLUSION: There are important risk factors for death among critically
      ill patients with infectious diseases associated with AKI.

PMID- 18330733
TI  - Blood donor screening: how to decrease the risk of transfusion-transmitted
      hepatitis B virus?
AB  - QUESTIONS UNDER STUDY: The risk of transfusion-transmitted HBV remains
      significant in Switzerland, where routine screening for hepatitis B virus (HBV)
      in blood donations relies solely on serological hepatitis B surface antigen
      (HBsAg) testing. This study was designed to determine the prevalence of anti
      hepatitis B core (anti-HBc) and HBV nucleic acid testing (NAT) positive donations
      in two different Swiss donor populations, to help in deciding whether
      supplemental testing may bring additional safety to blood products. METHODS: In a
      first population of donors, 18143 consecutive donations were screened initially
      for HBsAg, anti-HBc (with one EIA assay) and with HBV NAT in minipools of 24
      donations. The screening repeatedly reactive anti-HBc donations were then
      "confirmed" with two supplemental anti-HBc assays, an anti-hepatitis B surface
      assay (anti-HBs) and with single donation HBV NAT. In a second population of
      donors, 4186 consecutive donations were screened initially with two different
      anti-HBc assays in addition to the mandatory HBsAg screening test. The screening
      repeatedly reactive donations with at least one anti-HBc assay were tested for
      anti-HBs. RESULTS: In the first subset of 18143 donations, 17593 (97.0%) were
      negative for HBsAg, anti-HBc and HBV NAT in minipools. 549 (3.0%) were HBsAg and
      HBV NAT negative, but repeatedly reactive for anti-HBc. Of these 549 donations,
      287 could not be "confirmed" with two additional anti-HBc assays and were
      negative with an anti-HBs assay, as well as with single donation HBV NAT. Only
      211 (1.2% of the total screened donations) were "confirmed" positive with at
      least one of two supplemental anti-HBc assays. One repeatedly reactive HBsAg
      donation, from a first-time donor, was confirmed positive for HBsAg and anti-HBc,
      as well as with single donation HBV NAT. In the second subset of 4186 donations,
      4014 (95.9%) were screened negative for HBsAg and for anti-HBc, tested with two
      independent anti-HBc assays. 172 donations (4.1%) were HBsAg negative but
      repeatedly reactive with at least one of the two anti-HBc assays. Of these 172
      samples, 86 were reactive with the first anti-HBc assay only, 13 were reactive
      with the second anti-HBc assay only and 73 (1.7% of the total screened donations)
      were "confirmed" positive with both anti-HBc assays. CONCLUSION: The prevalence
      of anti-HBc "confirmed" positive donations in the two Swiss blood donor
      populations studied was low (<2%) and we found only one HBV NAT positive (HBsAg
      positive) donation among more than 18000. Concerning blood product safety, an
      increase in the deferral rate of less than 2% of anti-HBc positive, potentially
      infectious donors, would in our opinion make routine anti-HBc testing of blood
      donations cost-effective. There is however still a need for more specific assays
      to avoid an unacceptably high deferral rate of "false" positive donors. In
      contrast, the introduction of HBV NAT in minipools gives minimal benefit due to
      the inadequate sensitivity of the assay. It remains to evaluate more extensively
      the value of individual donation NAT, alone or in addition to anti-HBc, as
      supplemental testing in the context of several Swiss blood donor populations.

PMID- 18330734
TI  - Contact system activation in human sepsis - 47kD HK, a marker of sepsis severity?
AB  - AIM: This pilot study seeks to determine whether contact system activation (CSA)
      occurs in human sepsis patients and to characterise blood levels of the 47kD
      light chain of high-molecular weight kininogen (47kD HK). METHODS: Six
      consecutive patients with clinical suspicion of sepsis were evaluated on days 1,
      2, 3 and 6-8 for 47kD HK blood levels expressed in U/ml of whole blood and as
      percent of total HK. 47kD HK was measured in whole blood by quantitative
      immunoblot analysis. RESULTS: On study day 1 or 2, analysis of 47kD HK in U/ml of
      whole blood identified CSA in 3/6 patients. When 47kD HK levels were expressed as
      percent of total HK, 4/6 patients were identified with CSA before day 3. The
      degree of CSA as assayed by the presence of 47kD HK correlated with the severity
      of the systemic inflammatory syndrome (SIRS), i.e. mean CSA increased
      progressively from basal levels in healthy controls (0.08 U/ml or 10.4%) to
      patients without SIRS (0.10 U/ml or 15.1%), to patients with sepsis (0.12 U/ml or
      15.0%), and finally to patients in a combined category of severe sepsis and
      septic shock (0.13 U/ml or 17.4%). CONCLUSION: CSA, defined by increased 47kD HK,
      occurred early on in the course of sepsis in a subset of sepsis patients. 47kD HK
      levels, an indicator of bradykinin release, correlated with sepsis severity.
      Future larger studies will need to evaluate the role of 47kD HK as a biomarker
      for both prognosis and treatment response in human sepsis..

PMID- 18330735
TI  - Patients with schizophrenia and their finances: what they earn and own.

PMID- 18330737
TI  - [Turkish Journal of Psychiatry. Foreword].

PMID- 18330736
TI  - Clinical and laboratory findings in the diagnosis of bacterial pneumonia in
      children.

PMID- 18330738
TI  - [Peripheral blood T-lymphocyte and T-lymphocyte subset ratios before and after
      treatment in schizophrenia patients not taking antipsychotic medication].
AB  - OBJECTIVE: Immune system abnormalities in schizophrenia have been previously
      studied. According to the present point of view, an infection or autoimmune
      process might be occurring in the form of cellular and/or humoral immune system
      abnormalities in schizophrenia. Furthermore, several effects of antipsychotic
      medication on the immunological profile of schizophrenic patients have been
      demonstrated. The present study aimed to compare the total T-lymphocytes level
      and the T-lymphocyte subset ratios in schizophrenia patients not treated with
      antipsychotics and healthy controls. The relationship between disease duration,
      symptom severity, and treatment response and T-lymphocyte profiles were
      investigated. METHODS: The study included 14 patients (11 antipsychotic naive, 3
      antipsychotic free for at least 6 months) diagnosed with schizophrenia or
      schizophreniform disorder that were compared to age- and sex-matched healthy
      controls in terms of the total T-lymphocytes level and T-lymphocyte subset ratios
      using flow-cytometry. The relationship of the T-lymphocyte profiles, to disease
      duration and treatment response was investigated. RESULTS: The groups were not
      different in terms of total T-lymphocytes level and T-lymphocyte subset ratios;
      however, the antipsychotic naive patients and the group with disease duration < 2
      years had lower rates of T8-lymphocytes. Total T-lymphocytes and the T8
      lymphocyte ratio increased after treatment. Clinical improvement was correlated
      with total T-lymphocytes and the T4-lymphocyte subset ratio. CONCLUSION: Cellular
      immune system abnormalities in schizophrenia may be intrinsic factors. Changes in
      the cellular immune system are associated with treatment response and might be
      candidates for biological markers.

PMID- 18330739
TI  - [Comparison of cerebral blood flow in children with obsessive compulsive disorder
      and attention deficit hyperactivity disorder].
AB  - OBJECTIVE: It has been reported that both obsessive-compulsive disorder (OCD) and
      attention deficit hyperactivity disorder (ADHD) might be related to impairments
      in frontal-striatal brain circuits. Besides, these two disorders are frequently
      comorbid. However, there are no published studies directly comparing the
      neurobiological findings in these two disorders. The objective of the study was
      to investigate the differences in cortical blood flow between patients with OCD
      and ADHD. METHOD: Thirteen drug-naive OCD subjects (mean age +/- SD: 10.4 +/-
      2.8), and 13 drug-naive ADHD subjects (mean age +/- SD: 10.5 +/- 2.2) were
      included in the study. Cerebral blood flow (CBF) was evaluated with Tc-99m
      hexamethylpropyleneamine oxime (Tc99m HMPAO) brain single photon emission
      tomography (SPECT) during standard resting conditions in all cases. P value was
      set to <.006 after Bonferroni correction. RESULTS: OCD cases had significantly
      higher right prefrontal (p=.003) CBF than ADHD cases. There were no significant
      CBF differences in other brain regions. OCD symptom severity was not related to
      CBF. DISCUSSION: This is one of the very few studies which directly investigated
      brain imaging in pediatric OCD subjects. Results are consistent with previous
      studies reporting increased prefrontal CBF in OCD subjects. We also found that,
      consistent with the previous literature, ADHD subjects had lower prefrontal
      cortex CBF. Studies which compare subjects with comorbid ADHD and OCD with pure
      forms of these disorders are necessary to have a better understanding of
      similarities and differences of these two disorders.

PMID- 18330740
TI  - [Prediction of depression by locus of control, learned resourcefulness and
      sociotropy-autonomy in hemodialysis patients].
AB  - OBJECTIVE: The aims of the present study were to investigate the effects of
      various personality variables, namely, the locus of control beliefs, learned
      resourcefulness and sociotropy-autonomy in the prediction of the level of
      depressiveness in hemodialysis patients. The dependent variable of the study was
      not the depression but the level of depressiveness measured by the Beck
      Depression Inventory. METHOD: Seventy one permanent hemodialysis outpatients in a
      treatment center in Ankara participated in the study [43 females and 28 males
      with mean (+/-SD) ages of 44 (+/-9.68) and 52.6 (+/-7.8), respectively]. Beck
      Depression Inventory, Rotter's Internal External Locus of Control Scale,
      Rosenbaum's Learned Resourcefulness Scale, Sociotropy-Autonomy Scale and
      Demographic Information Form were given to the patients. F test and one way ANOVA
      were conducted to examine the effects of sex and age groups, respectively, and
      then Stepwise Multiple Regression Analysis was conducted for prediction of
      depressiveness levels. RESULTS: The oldest age group (defined as between 56-70
      ages) and females had higher depressiveness scores. External locus of control and
      low level of learned resourcefulness, an indicator of ineffective coping skills
      were the predictive variables of depressiveness in hemodialysis patients when
      age, sex, and total length of time on dialysis were controlled. On the other
      hand, other personality variables, sociotropy and autonomy were not significant
      predictors. CONCLUSION: Female patients and patients in the older age group were
      significantly more depressive, consistent with the literature, and the results
      were discussed in the light of the related literature.

PMID- 18330741
TI  - [Social anxiety level in acne vulgaris patients and its relationship to clinical
      variables].
AB  - OBJECTIVE: The purpose of this study was to determine the level of social anxiety
      in acne vulgaris patients and to examine its relationship to the sociodemographic
      and clinical characteristics of acne, as well as to depression, self-esteem, and
      negative automatic thoughts. METHOD: The study included 83 acne vulgaris patients
      from the dermatology outpatient unit of a university hospital and 58 healthy
      controls. Sociodemographic and clinical questionnaires, and the Global Acne
      Grading System (GAGS), Hospital Anxiety and Depression Scale (HADS), Liebowitz
      Social Anxiety Scale (LSAS), Rosenberg Self-Esteem Scale (RSES), and Automatic
      Thoughts Scale (ATS) were administered to both groups. RESULTS: The degree of
      social anxiety, social avoidance/withdrawal, general anxiety, depression, and
      negative automatic thoughts were significantly higher, and self-esteem was
      significantly lower in the acne patients. Among the 83 patients, scoring above
      the scales' cut-off points was as follows: 25.6% on the LSAS, 32.9% on the LSAS
      Anxiety Subscale, 27.7% on the LSAS-Avoidance Subscale, 36.1% on HADS, 30.1% on
      the HADS-Depression Subscale, and 50.6% on the HADS-Anxiety Subscale.
      Psychological symptoms were negatively correlated with age and level of education
      in the patient group; however no relationship was observed between the
      psychological symptoms, and gender, the severity of acne, or acne localization.
      The patients rated their symptoms more severely than did the clinicians; however,
      the subjective ratings of the patients were not correlated to their psychological
      symptoms. CONCLUSION: Acne vulgaris must be considered as an illness with the
      potential to negatively affect the psychological and emotional functioning of
      patients; therefore, routine psychiatric evaluation and psychological support
      should be part of the routine acne treatment plan.

PMID- 18330742
TI  - [Psychopharmacological treatment and quality of life in obsessive compulsive
      disorder].
AB  - OBJECTIVE: Obsessive compulsive disorder (OCD) is an illness that considerably
      influences the family, academic, occupational and social functioning of patients.
      In this study, we aimed to investigate the impact of psychopharmacological
      treatment on quality of life in patients with OCD. METHOD: Using the Yale-Brown
      Obsessive-Compulsive Scale (Y-BOCS), Hamilton Depression Rating Scale (HDRS) and
      the World Health Organization Quality of Life Measurement Instrument Short Form,
      Turkish Version (WHOQOL-Bref TR) we assessed 53 patients who met the DSM-IV
      criteria for OCD to establish baseline values. The patients were consecutively
      assigned to receive either sertraline (100-200 mg/day), fluvoxamine (200-300
      mg/day) or paroxetine (40-80 mg/day). We reassessed 36 (68%) of the initial group
      after 12 weeks. RESULTS: The scores of obsession, compulsion and depression
      severity at follow-up were significantly lower than those of baseline scores.
      There is no significant difference between the pre and post-treatment quality of
      life domain scores. While psychological health scores at follow-up was
      significantly associated with baseline HDRS scores (r=-0.35, p<0.05), social
      relationship scores at follow-up was significantly associated with baseline
      social relationship scores (r=0.63, p<0.001) and compulsion scores (r=-0.37,
      p<0.05). Regression analyses revealed that social relationship scores at follow
      up was associated with baseline compulsion severity whereas other follow-up
      quality of life domain scores were not predicted by any baseline variable.
      CONCLUSIONS: Clinical viewpoint and objective evaluations should be essential in
      the evaluation of treatment outcome, and quality of life researches may be
      important complement to clinical researches.

PMID- 18330743
TI  - [The prevalence of dementia three months after stroke and its risk factors].
AB  - OBJECTIVE: The aim of this study was to determine the prevalence of post-stroke
      dementia (PSD) and its possible clinical and sociodemographic risk factors 3
      months after the index stroke episode. METHODS: Among 147 patients who were
      hospitalized in the inpatient neurology clinic of Dicle University Faculty of
      Medicine with a diagnosis of stroke, 106 that met the inclusion criteria were
      included in the study 3 months after the index stroke. All patients underwent a
      detailed systemic and neurological examination, as well as a clinical interview
      in an effort to determine the sociodemographic features, and both vascular and
      non-vascular risk factors of stroke. Routine laboratory examinations and cranial
      imaging (computed tomography [CT] or magnetic resonance imaging [MRI]) were also
      conducted. The functional, clinical, and cognitive status of the patients were
      evaluated at the time of hospitalization and 3 months later with the Barthel
      Index, NIH Stroke Scale (NIHSS), and Mini Mental State Examination (MMSE),
      respectively. RESULTS: Of the 106 patients included in the study, 32 (30.2%) were
      diagnosed with PSD. Multivariate analyses revealed that increased age, presence
      of atrial fibrillation, multiple brain lesions, and cognitive and functional
      status during hospitalization predicted the development of PSD in this group of
      patients. CONCLUSION: The results corroborate previous findings that PSD is a
      common complication of stroke. Early recognition and treatment of PSD risk
      factors will definitely diminish the burden of stroke on society and help to
      improve patient quality of life.

PMID- 18330744
TI  - [Examination of the criterion validity of the MMPI-2 Depression, Anxiety, and
      Anger Content scales].
AB  - OBJECTIVE: Examination of the psychometric properties and content areas of the
      revised MMPI's (MMPI-2 [Minnesota Multiphasic Personality Inventory-2]) content
      scales is required. In this study the criterion-related validity of the MMPI-2
      Depression, Anxiety, and Anger Content scales was examined using the following
      conceptually relevant scales: The Beck Depression Inventory (BDI), Beck Anxiety
      Inventory (BAI), and State Triad Anger Scale (STAS). METHOD: MMPI-2 Depression,
      Anxiety, and Anger Content scales, and BDI, BAI, and STAS were administered to a
      sample of 196 students at Middle East Technical University (n= 196; 122 female,
      74 male). Regression analyses were performed to determine if these conceptually
      relevant scales contributed significantly beyond the content scales. The MMPI-2
      Depression Content Scale was compared to BDI, the MMPI-2 Anxiety Scale was
      compared to BAI, and the MMPI-2 Anger Content Scale was compared to STAS.
      RESULTS: The internal consistency of the MMPI-2 Depression Content Scale (alpha =
      0.82), the MMPI-2 Anxiety Content Scale (alpha = 0.73), and the MMPI-2 Anger
      Content Scale (alpha = 0.72) was obtained. Criterion validity of the 3 analyzed
      content scales was demonstrated for both males and females. CONCLUSION: The
      findings indicated that (1) the MMPI-2 Depression Content Scale provides
      information about the general level of depression, (2) the MMPI-2 Anxiety Content
      Scale assesses subjective anxiety rather than somatic anxiety, and (3) the MMPI-2
      Anger Content Scale may provide information about the potential to act out. The
      findings also provide further evidence that the 3 conceptually relevant scales
      aid in the interpretation of MMPI-2 scores by contributing additional information
      beyond the clinical scales.

PMID- 18330745
TI  - [Adaptation, validity, and reliability of the Metacognition Questionnaire-30 for
      the Turkish population, and its relationship to anxiety and obsessive-compulsive
      symptoms].
AB  - OBJECTIVE: The present study aimed to evaluate the psychometric properties of the
      short form of the Metacognition Questionnaire (MCQ-30) in a population of Turkish
      university students. The metacognitions questionnaire (MCQ) measures individual
      differences in a selection of metacognitive beliefs, judgments, and monitoring
      tendencies considered important in the metacognitive model of psychological
      disorders. METHOD: The study included 850 university students from 15 Turkish
      universities. Mean age age of the participants was 21.22 years, 282 (33.17%) were
      female, and 568 (66.82%) were male. RESULTS: Construct validity was evaluated by
      exploratory and confirmatory factor analysis (CFA). Exploratory factor analysis
      revealed that the Turkish version of MCQ-30 has 5 components, which is same
      factor structure as the original form. In addition, the fit indices of CFA
      suggested an acceptable fit to a 5-factor model consistent with the original MCQ
      30. The Turkish MCQ-30 showed acceptable to good test-retest reliability,
      internal consistency, and convergent validity. Significant positive relationships
      between the subscales of MCQ-30 and measures of anxiety and obsessive-compulsive
      symptoms provided further support for the convergent validity of the Turkish
      version. Moreover, significant negative correlations were observed between age
      and the MCQ-30 subscales, and the effect of gender was significant on some of the
      subscales. CONCLUSION: The psychometric properties of the Turkish version of MCQ
      30 showed that the instrument is a valuable additional tool for the assessment of
      metacognition in Turkey.

PMID- 18330746
TI  - [The role and importance of cognitive symptoms in bipolar disorder].
AB  - OBJECTIVE: Our aim was to review evidence of the role of cognitive deficits in
      bipolar disorder and their relationship to other factors, such as disorder
      variables, treatment, additional diagnoses, genetic risk, and brain imaging
      findings. METHOD: Studies that examined cognitive dysfunction in bipolar disorder
      and its relationship to the variables of clinical, genetic, and bipolar disorder
      subtypes, as well as neuro-anatomical and neuro-functional evidence have been
      reviewed. Findings from our own studies have also been used while conducting the
      review. RESULTS: In bipolar disorder, deficits in executive functions, memory,
      and attention persist in the euthymic state. The number of episodes and the
      course of the disorder seem to be related to the severity of memory dysfunction
      and psychomotor slowness. However, symptoms of cognitive dysfunction are present
      at the onset of the disorder. Moreover, cognitive dysfunction has been observed
      in the healthy relatives of bipolar disorder patients. Cognitive dysfunction in
      bipolar disorder is associated with functional and possibly structural anomalies
      in some parts of the brain, such as the frontal and cingulate cortex. Some recent
      studies reported a relationship between symptoms of cognitive dysfunction and
      genetic variations in bipolar disorder. CONCLUSION: Today, the presence of
      cognitive deficits in bipolar disorder is widely accepted; however, evidence of
      the neurobiological and clinical correlates of cognitive symptoms is still
      limited. More studies are needed to investigate the relationship between
      cognitive dysfunction in bipolar disorder and risk. Genetic studies are just now
      amending our body of knowledge. There have been many conflicting results reported
      by brain imaging studies. Different brain imaging approaches and genetic methods
      should be used with more specific cognitive and social-emotional tasks for
      increasing our knowledge about the nature of cognitive deficit in bipolar
      disorder.

PMID- 18330747
TI  - [Suggestion of a new diagnostic category: posttraumatic embitterment disorder].
AB  - Psychological reactions to negative life events have been among the most
      interesting subjects to researchers for a long time. In recent years post
      traumatic stress disorder (PTSD), in particular, has been the focus of numerous
      studies. This disorder is defined as a reaction to an event that is accepted as
      traumatic by almost everyone, to an extraordinary life-threatening event, or to a
      disaster. Psychological reaction to events, which are not directly life
      threatening, is classified as adjustment disorder and is rarely diagnosed in
      clinical practice. As a result of experiencing such non-life threatening events,
      PTSD is claimed to be an adjustment disorder as well. Immigrants frequently
      report a depressive state in which physical symptoms are in the foreground
      accompanied by social withdrawal and diminished energy. Negative life events,
      which are not life threatening and are not experienced everyday, can impair
      mental health so that the above state may worsen and an immigrant may have a
      reduction in his performance at work. This state, which is accompanied by such
      symptoms as embitterment, feelings of injustice, repeated intrusive memories of
      critical events (injustice at work place, loss of a job, discrimination in a
      public office, etc.), phobic symptoms, and avoidance behavior towards the place
      or persons related to the event, might best be described by the term,
      posttraumatic embitterment disorder (PTED). This disorder, which was initially
      described in immigrants from East Germany following the fall of the Berlin Wall,
      and which does not exactly match the diagnostic criteria of adjustment disorder
      or PTSD, is presented in a case vignette and its differential diagnosis is
      discussed.

PMID- 18330748
TI  - [Evoked potentials and regional cerebral blood flow changes in conversion
      disorder: a case report and review].
AB  - Conversion disorder is defined as the presence of functional impairment in motor,
      sensory or neurovegetative systems which cannot be explained by a general medical
      condition. Although the diagnostic systems emphasize the absence of an organic
      basis for the dysfunction in conversion disorder, there has been a growing
      interest in the specific functional brain correlates of conversion symptoms in
      recent years, particularly by examining neuroimaging and neurophysiological
      measures. In this case report, regional cerebral blood flow changes and evoked
      potentials of a patient with conversion symptoms are presented. Somatosensory
      evoked potentials (SEP) of this patient with conversion disorder who had signs of
      movement disorder revealed that the latency to N20, P 25 waves were in normal
      limits while the amplitudes of the P25 and N33 components were extremely high
      (giant SEP). Regional cerebral blood flow assessment revealed hypoperfusion in
      the left parietal and temporal lobes of the brain. Three months after the first
      assessment, the control scans showed that the left parietal hypoperfusion
      disappeared while the left temporal hypoperfusion was still present. The
      following SEP evaluations which were repeated twice in three months intervals
      after the initial recordings, showed the persistence of the abnormalities in
      somatosensorial measures. The neurophysiological and neuroimaging findings in
      conversion disorder were reviewed and the results of the evaluations of this case
      were discussed in this article.

PMID- 18330749
TI  - Vascular endothelial growth factor and tumor necrosis factor genes polymorphisms
      in Turkish patients with sarcoidosis.
AB  - Polymorphism at -857 locus of tumor necrosis factor (TNF)-alpha gene is
      considered to be a predisposition factor in sarcoidosis and held responsible for
      pathogenesis of the disease and polymorphism at +813 locus of vascular
      endothelial growth factor (VEGF) gene is thought to decrease predisposition to
      sarcoidosis. In our study, we examined and compared these polymorphisms in
      healthy Turkish control subjects and Turkish patients with sarcoidosis. We
      examined gene polymorphisms in 70 cases which were histopathologically diagnosed
      as sarcoidosis and 80 healthy subjects without any history of a chronic disease.
      5 cc of blood were collected in tubes with EDTA from all of the cases. TNF-alpha
      857 gene polymorphism and VEGF+813 gene polymorphism were determined using PCR +
      RFLP method after DNA isolation. TNF-alpha promoter polymorphism, at position 
      857, revealed no differences in genotype and allele frequency between patients
      and control subjects but more relapses were found in sarcoidosis patients who
      have this polymorphism. Considering the VEGF polymorphism at position +813, we
      observed a significant increase in the frequency of rarer T allele at this
      position in healthy subjects compared with sarcoidosis patients. VEGF gene
      polymorphism at +813 locus may diminish susceptibility to sarcoidosis. TNF-alpha
      857 gene polymorphism influence severity of the disease.

PMID- 18330750
TI  - [Sensitivity of cough with capsaicin in smokers].
AB  - In this study, effect of long term smoking on sensitivity of cough reflex was
      investigated. Healthy, current smoker male and female was evaluated by capsaicin
      cough challenge test and they were compared with healthy, non-smoker persons with
      similar age and gender, prospectively. In current smokers, there were 50 male and
      39 female, in non-smoker control group, there were 20 male and 21 female. Mean
      and log C5 dosage in current smoker and non-smoker groups and mean and log C5
      dosage in current smoker according to gender were calculated by using Mann
      Whitney U-test. Results of capsaicin cough challenge test in current and non
      smoker groups were evaluated by using Pearson Chi-Square test and Fisher's Exact
      test. In current smokers comparison of results of capsaicin cough challenge test
      with smoking history (age with first smoking, duration, pocket year and smoking
      per day) was evaluated by using Mann-Whitney U-test. Mean C5 and mean log C5
      dosage were found decreased in current smokers when they were compared to control
      group (p< 0.00). In current smoker group mean C5 and mean log C5 dosage were
      found decreased in male (p< 0.002). When the results of capsaicin cough challenge
      test were compared between current smoker and control groups, sensitivity of
      cough reflex in concentration with 0.49, 0.98, 1.95, 3.9, 7.8, 15.6 microM was
      significantly decreased in current smoker group. Also there was a significant
      correlation between concentration with 0.98, 1.95, 3.9, 7.8, 15.6, 31.2 microM,
      and duration of smoking and pocket year of smoking. Also there was a correlation
      between concentration with 15.6, 31.2, 62.5, 125 microM and smoking per day. This
      results were correlated with hypothesis about inhibition of C-fibers with nicotin
      or decrease of C-fibers' sensitivity due to induction of neuropeptide wasting.

PMID- 18330751
TI  - [Prognostic factors in small cell lung cancer].
AB  - In order to find out prognostic factors and treatment results in small cell lung
      cancer (SCLC), 40 patients diagnosed in one year period were prospectively
      analysed. Following history and physical examination, patients were grouped
      according to ECOG performance scale and underwent Chest X-ray and thoracic
      computerized tomography (CT). Complete blood count, biochemical analyses, tumor
      markers were taken. Abdominal USG or CT, bone scintigraphy, cranial CT or MRI and
      bone marrow biopsy were made for detection of metastases. Limited stage patients
      received chemotherapy and thoracic RT, whereas cases with extensive disease
      received chemotherapy. Nineteen cases had limited and 21 had extensive disease.
      When laboratory findings between 2 stages were compared, LDH, SGOT and GGT were
      significantly higher in extensive stage (p= 0.005, 0.015, 0.001, respectively).
      Overall median survival was 6 +/- 1 months, cumulative survival in 6 and 12
      months were 39% and 20.72%, respectively. Median survival was 10 +/- 2 months in
      limited stage and 3 +/- 1 months in extensive stage, with a statististically
      significant difference. Univariate analyses showed that incresed LDH, CA15-3, GGT
      and SGOT levels, hipoproteinemia and poor performance scale were poor prognostic
      signs (p= 0.024, 0.032, 0.047, 0.013, 0.021 ve 0.013, respectively), however
      multivariate analyses revealed no significant difference. Other blood tests,
      pleural effusion, age, mediastinal lymph node metastases and weight loss had no
      prognostic effect. Stage was found to be progniostic factor with both univariate
      and multivariate analyses (p= 0.045).

PMID- 18330752
TI  - [The characteristics of smoking habit among patients evaluated at our outpatient
      clinic].
AB  - To determine the prevalence of cigarette smoking, to examine the risk factors
      affecting smoking amongst adults and to assess the opinion of patients about
      quitting smoking who were evaluated at our outpatient clinic. Six hundred fifty
      nine patients who were evaluated at our outpatient clinic between June 2005 and
      June 2006 were included in the study. This is a cross-sectional study that
      evaluates prevalence of smoking. Data gathered by applying face to face
      questionnaires. The mean age of 659 participants [417 (63.3%) males and 242
      (36.7%) females] was 53.1 +/- 16.2 years. The prevalences were; 33% (n= 218)
      smokers, 39% (n= 258) ex-smokers and 28% (n= 183) non-smokers. Smoking prevalence
      under age of 50 was significantly higher (p= 0.0001). There was a positive
      significant relation between education and smoking amongst women, but this
      relationship was not significant amongst men. The most common reason for
      beginning smoking was because of friends (72%). 86% wanted to quit smoking. 48.9%
      tried to quit smoking but couldn't be successful. The prevalence of active
      smoking and quit smoking among patients who applied to pulmonary medicine
      outpatient clinic were 33% and 28%, respectively. The ratio of smoking and
      smoking pack-years was higher among men. Eighty-six percent of patients wanted to
      quit, 25% tried to quit but could not be successful, and 49% quit smoking but
      began smoking again. According to these findings, patients who were smoking
      wanted to quit but couldn't be successful without a professional help. We planned
      to found a smoking cessation outpatient clinic at our department.

PMID- 18330753
TI  - [Homocysteine levels in patients with obstructive sleep apnea syndrome].
AB  - The exact mechanism of development of cardiovascular disease in patients with
      obstructive sleep apnea syndrome (OSAS) remains to be unknown. The role of
      homocysteine in atherosclerotic disease process has become well established over
      the past ten years. Our aim was to study to compare homoscysteine levels between
      OSAS and control levels. Sixty-two subjects with OSAS and twelve similar controls
      in age, gender, body mass index, smoking and coronary heart disease were included
      in this prospective study. Serum levels of homocysteine (13.5 +/- 6.0 micromol/L
      vs. 10.2 +/- 2.9 micromol/L, p= 0.03) in the OSAS group were significantly
      greater than those in the control group. Logistic regression analyses showed that
      OSAS (Odds ratio: 9.08 95% CI 2.347-35.120; p= 0.001) was independent risk
      factors for high levels of serum homocysteine in age, smoking status, diabetes
      mellitus and coronary heart disease. We conclude that homocysteine may be an
      important factor for development of cardiovascular disease in patients with OSAS.

PMID- 18330754
TI  - [The diagnostic efficiency of multislice CT virtual bronchoscopy in detecting
      endobronchial tumors].
AB  - In this study, the diagnostic efficiency of virtual bronchoscopy, which is a new
      and helpful method to conventional fiberoptic bronchoscopy, has been investigated
      for endobronchial lung tumors and its clinical applications are discussed. 36
      patients with clinically suspected lung cancer (28 males, 8 females, mean age 61;
      range from 39 to 74) underwent multislice computed tomography (MSCT) virtual
      bronchoscopy and then conventional bronchoscopy on the same day. For all
      patients, investigators were uninformed about results of conventional
      bronchoscopy. Sensitivity, specificity, positive and negative predictive values
      of virtual bronchoscopy were calculated using conventional bronchoscopy results
      as standard reference values. In 12 patients, conventional bronchoscopy did not
      show pathologic findings. In 24 cases pathologic findings were detected; mucosal
      infiltration was observed in three cases, vegetating lesions were detected in 21
      cases. Review of these 21 cases demonstrated preocclusive stenosis in five and
      various degrees of luminal stenosis in 16 cases. All 21 tumoral lesions observed
      with conventional bronchoscopy were also detected with virtual bronchoscopy.
      Retrospective evaluation of six lesions visualized with virtual bronchoscopy but
      not detected with conventional bronchoscopy showed that they consisted of highly
      viscous mucous secretion. No abnormalities were detected on both conventional and
      virtual bronchoscopy in six patients. Three mucosal infiltrations observed on
      conventional bronchoscopy were not visualised on virtual bronchoscopy. The
      sensitivity of MSCT virtual bronchoscopy was 88% and specificity was 50% which is
      concordant with the literature. Positive predictive value, negative predictive
      value and accuracy was found 78%, 66% and 75%, respectively.

PMID- 18330755
TI  - [The evaluation to relationship between serum vascular endothelial growth factor
      (VEGF) level, metastases and other tumor markers in patients with lung cancer].
AB  - Vascular endothelial growth factor (VEGF) is a potent mediator of angiogenesis.
      Increased expression of VEGF may be associated with advanced stage and poor
      prognosis in patients with lung cancer. We investigated the relationship between
      serum VEGF level and lung cancer stage. We also studied the correlation between
      serum VEGF level and some other tumor markers. Forty newly diagnosed lung cancer
      (31 non-small cell, 9 small cell) patients and 25 age-matched controls were
      enrolled in this study. Serum VEGF levels of lung cancer group (345.16 +/- 159.36
      pg/mL) were significantly higher than that of the control group (230.36 +/- 47.87
      pg/mL) (p< 0.001). The area under the ROC curve was 0.727 (p< 0.05) for serum
      VEGF threshold of 249.8 pg/mL predictive sensitivity and specificity, for lung
      cancer were respectively 70.0% and 76.0%. There were no significant relationship
      between serum VEGF level and age, gender, histologic type, lung cancer stage,
      distant metastases and site of metastases. In addition, there were no correlation
      between serum VEGF level and other tumor markers (NSE, CYFRA 21-1, CEA, CA125,
      LDH).

PMID- 18330756
TI  - [The role of positron emission tomography (PET) in mediastinal staging of non
      small cell lung cancer].
AB  - Mediastinal lymph node metastasis (MLNM) is the most important prognostic factor
      and guide to the treatment in non-small cell lung cancer (NSCLC) patients with no
      distant metastasis. As a non invasive method, using of positron emission
      tomography (PET) to evaluate NSCLC is increasing. We aimed to compare results of
      PET and mediastinoscopy to reveal effectiveness of PET in the mediastinal staging
      of NSCLC patients. PET was performed to 100 operable NSCLC patients between 2004
      and 2006. Later, standard cervical mediastinoscopy was performed to all of the
      patients. Twenty-six patients who detected MLNM at mediastinoscopy were referred
      to oncology clinic for neoadjuvant or definitive chemo-radiotherapy. Other 74
      patients underwent thoracotomy and performed lung resection and mediastinal
      lymphatic dissection. Sensitivity and specificity rates for detecting mediastinal
      lymphatic metastasis of PET and mediastinoscopy were compared. There were 89 male
      and 11 female with mean age of 59 years. Sensitivity, specificity, positive
      predictive value, negative predictive value and accuracy rates were calculated as
      74%, 76%, 59%, 86% and 76% respectively for PET and 83%, 100%, 100%, 93% and 95%
      respectively for mediastinoscopy. Accuracy rate of PET is not sufficient and
      mediastinoscopy is still the gold standard to evaluate mediastinal staging of
      NSCLC, at present.

PMID- 18330757
TI  - Evaluation of the weaning process in COPD patients with acute respiratory
      failure.
AB  - Based on our observations in chronic obstructive pulmonary disease (COPD)
      patients admitted to our respiratory intensive care unit due to acute respiratory
      failure suggesting a significant variation in weaning duration (WD), we conducted
      a retrospective cohort study in such patients. Fifty-nine patients successfully
      extubated following invasive mechanical ventilation were included. Syncronized
      intermittent mandatory ventilation plus pressure support ventilation was used as
      the weaning mode in mostly. Study population was divided into two groups. Group
      1: patients with a WD < or = 24 hours (n= 32), Group 2: patients with a WD > 24
      hours (n= 27). Groups were compared with respect to demographics, vital signs,
      arterial blood gases, laboratory values, and the treatment characteristics. The
      average WD was 13 +/- 8 and 58 +/- 34 hours in group 1 and group 2, respectively
      (p< 0.001). In the logistic regression analysis, the following factors were found
      to have a predictive value for a WD > 24 hours: elevated baseline heart rate,
      alkaline pH at the day of weaning, duration of midazolam infusion, and
      emphysematous findings on chest X-ray. In conclusion, whether the WD in COPD
      patients is less or greater than 24 hours is not only determined by the medical
      treatment administered, but also by the patient and disease characteristics.

PMID- 18330758
TI  - Effectiveness of gemcitabine as second-line chemotherapy in non-small cell lung
      cancer.
AB  - The role of a second-line chemotherapy after an initial treatment with a platinum
      based regimen remains largely undefined. In this retrospective clinical
      effectiveness study, gemcitabine as monotherapy was evaluated in the second-line
      chemotherapy in 34 non-small cell lung cancer (NSCLC) cases that had been
      previously received chemotherapy and did not respond to the treatment or
      presented with relapses. Gemcitabine was given intravenous at a dose of 1250
      mg/m2 on days one, eight every three weeks. Median age was 50 years and squamous
      cell carcinoma was the most common malignancy (44.1%). No patient had a complete
      response, 7 (20.6%) patients had a partial response. The median survival was 29
      weeks. The 1-year survival probability was estimated at 26.5%. Median time to
      disease progression was 13 weeks. Gemcitabine was well tolerated in this patient
      population. Among totally 119 chemotherapy cycles, we observed grade 3 and 4
      toxicities only in 2.5% of cycles. As a result of the study, single agent
      gemcitabine is found to be tolerable and to have moderate effectiveness in the
      second-line chemotherapy in NSCLC. It should be placed among treatment options.

PMID- 18330759
TI  - Determining the relation between N-acetyltransferase-2 acetylator phenotype and
      antituberculosis drug induced hepatitis by molecular biologic tests.
AB  - Tuberculosis is treated with a group of drugs that need to be used over a long
      period of time and isoniazid is the major drug in this group. Antituberculosis
      drug-induced hepatitis is the most serious problem in tuberculosis treatment. The
      enzyme N-acetyltransferase-2 (NAT-2) metabolizes isoniazid in the liver so it is
      considered to cause hepatotoxicity. The association of polymorphic NAT acetylator
      status and antituberculosis drug-induced hepatitis is discussed. To determine
      whether acetylator status is a risk factor for antituberculosis drug-induced
      hepatitis, we genotyped NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms in
      100 patients diagnosed with tuberculosis. 70 patients who did not develop
      hepatotoxicity were classified as the control group, and 30 patients who were
      diagnosed with antituberculosis drug-induced hepatitis were classified as the
      study group. NAT2 polymorphisms were divided into three phenotypic groups
      according to the analytical results obtained. Among the 70 patients constituting
      the control group; 14 (20%), 37 (52.9%), 19 (27.10%) patients were rapid,
      intermediate and slow acetylators respectively. In contrast, among the patients
      constituting the study group; 3 (10%), 4 (13.3%), 23 (76.7%) patients were rapid,
      intermediate and slow acetylators. The difference was statistically significant
      when the control and study groups were compared for their acetylator status. The
      proportion of slow acetylators was much higher in the study group. In conclusion,
      NAT2 acetylator phenotype analysis by molecular biology methods prior to medical
      treatment for tuberculosis, can be used both for determining the high-risk group
      of patients who may develop hepatotoxicity and for closer follow-up during
      treatment period.

PMID- 18330760
TI  - Catamenial hemoptysis.
AB  - Catamenial hemoptysis is a rare condition that is associated with the presence of
      intrapulmonary or endobronchial endometrial tissue. We describe a case of
      endobronchial endometriosis with catamenial hemoptysis. The patient was a 22
      years-old girl presented with recurrent hemoptysis episodes for the last two
      years. Bronchoscopic examination was performed within first days of menses, and
      indicated multiple purplish-red submucosal patches in distal one third of trachea
      and bilateral bronchial trees that bled easily when touched. The cytological
      evaluation of the bronchial brushing specimens demonstrated clusters of small
      cuboidal cells consistent with an endometrial origin. Follow-up bronchoscopic
      examination at the end of the menstrual cycle revealed that the previous
      tracheobronchial lesions disappeared. The patient was treated with Gonadotropin
      Releasing Hormone (GnRH) analogues and hormones including estrogen and
      progesterone therapy. Recurrent hemoptysis stopped following the medical
      treatment.

PMID- 18330761
TI  - Endobronchial metastases from a leiomyosarcoma of the uterus.
AB  - A 63-year-old woman presented with dyspnea, non-productive cough and chest pain.
      On computed tomography of the thorax, near total atelectasis of the left lung was
      reported. On bronchoscopic examination, a mass lesion was observed in the mucosa
      of the left main bronchus leading to near total obstruction. Her medical history
      revealed that she had been treated with total abdominal hysterectomy and adjuvant
      radiation therapy for a leiomyosarcoma of the uterus one year ago. She was
      diagnosed as having a metastatic leiomyosarcoma and was treated with palliative
      radiation therapy. Six months later, she presented with disseminated disease
      involving the thorax and the pelvis. She refused further treatment and died one
      month later. Patients with leiomyosarcomas of the uterus might follow an
      aggressive clinical course, with relatively early metastases at unusual sites.

PMID- 18330762
TI  - [Pregnancy and hydatid cyst].
AB  - Cyst hydatid disease (CHD) can be localized in every organ and frequently seen in
      Turkey. Twenty weeks pregnant woman was admitted with hemoptysis and dyspnea.
      Chest X-ray revealed bilateral homogeneous dansities. We planned to end pregnancy
      or follow until term, as diagnosis of CHD. The patient refused delivery. Eleven
      months later she was admitted with haemoptysis and syncope. Chest X-ray showed
      cavitary lesion, pleural effusion, pneumothorax in right lung and another
      cavitary lesion in left. Tube thoracostomy performed with the diagnosis of
      perforated cyst hydatid (CH) and the patient operated. CH may enlarge in
      pregnancy. Cyst rupture can cause anaphylactic shock and hemoptysis. Pregnancy
      and CHD occur occasionally together and there is no consensus about treatment.

PMID- 18330763
TI  - Giant atypical lipomatous tumor of the mediastinum.
AB  - Atypical lipomatous tumors, so-called well differentiated liposarcomas are the
      intermediate or locally aggressive form of adipocytic tumors. Mediastinum is an
      uncommon localization for these tumors and they have a potential risk of
      recurrence following excision. We herein report a case with a giant atypical
      lipomatous tumor located at the mediastinum that was surgically excised. The
      patient is free of recurrence and asymptomatic at postoperative 17 months.
      Surgery remains as the treatment of choice for mediastinal liposarcomas.

PMID- 18330764
TI  - Youngest netherton patient with infantile asthma.
AB  - Netherton syndrome is a very rare disorder characterized with icthyosis, atopy,
      bamboo hair and intermittant aminoaciduria. The specifity of clinical and
      histopathological features of netherton syndrome is low in neonates and young
      infants who presents with predominating erythrodermia. Being the youngest infant
      presenting with the symptoms of infantile asthma we found it worth to report a
      six months old girl presenting with the feature of severe respiratory distress,
      generalized erythrodermia, and brittle hair.

PMID- 18330765
TI  - Distant forearm muscle metastasis from squamous cell lung carcinoma.
AB  - A case of a 59-year-old man with a distant forearm muscular metastasis due to
      squamous cell lung carcinoma is presented. Fourteen months after a right
      pneumonectomy the patient was readmitted with a mass in the right forearm and
      pain in the right elbow during flexion. He underwent an en bloc wide resection of
      the tumor, which was confirmed to be metastatic. Twelve months after excision and
      adjuvant chemoradiotherapy he remains in complete remission.

PMID- 18330766
TI  - New trends in the diagnosis and treatment in parapneumonic effusion and empyema.
AB  - Despite treatment with antibiotics, patients with complicated parapneumonic
      effusion (PPE) and empyema have an increased morbidity and mortality due at least
      in part to inappropriate management of the pleural effusion. PPE should be
      considered in all patients with pneumonia as antibiotic therapy is being
      initiated. If the diaphragms cannot be seen throughout their length on the chest
      radiographs, a lateral decubitus radiograph, ultrasonography or computerized
      tomography scan should be obtained. If the effusion is more than 10 mm in
      thickness, a therapeutic thoracentesis should be performed. If the fluid cannot
      all be removed and the characteristics of the pleural fluid indicate a poor
      prognosis, a chest tube should be inserted. If the drainage is incomplete due to
      loculation of the PPE intrapleural fibrinolytics or thoracoscopy should be
      performed. If the lung does not reexpand completely with thoracoscopy, then
      decortication should be performed without delay.

PMID- 18330767
TI  - [Monoclonal gammopathy of undetermined significance (MGUS) related to miliary
      tuberculosis and spinal tuberculosis (Pott's disease)].

PMID- 18330768
TI  - Impulsive-compulsive buying disorder: clinical overview.
AB  - Impulsive-compulsive buying disorder (ICBD) is an impulse control disorder not
      otherwise specified (ICD-NOS) characterized by impulsive drives and compulsive
      behaviours (buying unneeded things), personal distress, impaired social and
      vocational functioning and financial problems. Despite being described in the
      19th century, serious attention to ICBD began only in the last decade with the
      first epidemiological and pharmacological investigation. Biological, social and
      psychological factors contribute to the aetiology of ICBD. Cognitive-behavioural
      therapy and selective serotonin re-uptake inhibitors are currently considered the
      more effective interventions in the treatment of ICBD. The present review aims to
      provide a broad overview of the epidemiology, aetiology, phenomenology and
      treatment options of ICBD.

PMID- 18330769
TI  - Adverse incidents in acute psychiatric inpatient units: rates, correlates and
      pressures.
AB  - OBJECTIVE: This paper reports findings from a multicentre service evaluation
      project conducted in acute psychiatric inpatient units in NSW, Australia. Overall
      rates of aggression, absconding and early readmission are reported, as well as
      length-of-stay profiles and associations between these outcomes and selected
      sociodemographic and clinical characteristics routinely collected by health
      services. METHOD: Data from the 11 participating units were collected for a
      12month period from multiple sources, including electronic medical records,
      routine clinical modules, incident forms, and shift based project-specific logs.
      For the current analyses, two admission-level datasets were used, comprising
      aggregated patient-level events (n=3242 admissions) and basic sociodemographic,
      clinical, admission and discharge information (n=5546 admissions by 3877
      patients). RESULTS: The participating units were under considerable strain: 23.3%
      of admissions were high acuity; 60.4% had previous hospital stays; 47.6% were
      involuntary; 25-30% involved adverse incidents; bed occupancy averaged 88.4%;
      median length of stay was 8 days (mean=14.59 days); and 17.4% had a subsequent
      early readmission. Reportable aggressive incidents (11.2% of admissions) were
      intermittent (averaging 0.55 incidents per month per occupied bed) and associated
      with younger age, personality disorder, less serious aggression, longer periods
      of hospitalization, and subsequent early readmission. Less serious aggressive
      incidents (15.0% of admissions) were maximal in the first 24h (averaging 3.73
      incidents per month per occupied bed) and associated with younger age,
      involuntary status, bipolar and personality disorders, the absence of depression,
      and longer hospital stays. Absconding (15.7% of admissions) peaked in the second
      week following admission and was associated with drug and alcohol disorder,
      younger age, and longer periods of hospitalization. CONCLUSIONS: By examining
      relationships between a core set of risk factors and multiple short-term
      outcomes, we were able to identify several important patterns, which were
      suggestive of the need for a multi-level approach to intervention, shifting from
      a risk management focus during the early phase of hospitalization to a more
      targeted, therapeutic approach during the later phase. But the latter approach
      may not be achievable under current circumstances with existing resources.

PMID- 18330770
TI  - Use of pro re nata medications in acute inpatient care.
AB  - OBJECTIVES: Available evidence suggests that the use of 'as needed' (PRN; from
      the Latin pro re nata: for an occasion that has arisen) medications has remained
      a standard aspect of treatment in acute inpatient mental health units over a
      number of years despite lack of evidence from controlled clinical trials. The
      practice is one in which doctors and nurses are interdependent; that is, while
      doctors prescribe the medications, professional nurses are the ones who make the
      clinical decisions to administer them. The aim of the present study was to
      provide a detailed description of the circumstances surrounding the use of PRN
      medications across four inpatient units in Sydney. METHODS: The medical records
      of all patients admitted for >24h during a 2 month period were retrospectively
      audited for details regarding prescriptions and administrations of PRN
      medications. RESULTS: A total of 420 records were reviewed, producing a total of
      3868 PRN medication administrations. Ninety-seven per cent of all patients were
      prescribed PRN medications and 93.8% were prescribed regular medications. The
      most frequently prescribed medications were second-generation antipsychotics for
      regular use along with benzodiazepine for PRN use. Nearly 84% of patients
      received at least one PRN medication during their admission, while patients
      diagnosed with personality disorder received more PRNs per day. The most common
      reason for PRN administration was patient agitation. The results indicated poor
      documentation in the prescription and documentation of PRN administrations. Also,
      the findings show that a small subset of the patients (5%) received >30% of all
      PRN medications. CONCLUSION: PRN medication use has endured as standard practice
      and the results of the present study are consistent with the reported frequency
      of use increasing slightly over the years. The combination of second-generation
      antipsychotics as regular medications and benzodiazepines for PRN medication is
      consistent with recommended treatment guidelines. The small subset of patients
      who were overrepresented in the PRN administrations is noteworthy.

PMID- 18330771
TI  - Ethnic identification, social disadvantage, and mental health in
      adolescence/young adulthood: results of a 25 year longitudinal study.
AB  - OBJECTIVE: To examine the role of cultural identity and social
      disadvantage/childhood adversity in a birth cohort of 984 young people studied to
      the age of 25. METHODS: Data were gathered on mental health, cultural
      identification, socioeconomic factors and childhood adversity as part of a
      longitudinal study of a New Zealand birth cohort (the Christchurch Health and
      Development Study). RESULTS: Those with sole Maori identity had rates of disorder
      that were 1.28-fold higher than those of non- Maori; those of Maori/other
      identity had rates of disorder that were 1.57-fold higher than non- Maori.
      Regression analyses suggested that the elevated rates of mental disorder among
      Maori were largely explained by their higher exposure to socioeconomic
      disadvantage and childhood adversity. But even after adjustment, being of sole
      Maori identity was a protective factor that reduced rates of mental disorder
      among Maori. CONCLUSIONS: Risk and protective factors associated with the mental
      health of young Maori involve an interplay between levels of exposure to social
      disadvantage/childhood adversity and cultural identity, with secure cultural
      identity being a factor that may mitigate the effects of exposure to adversity.

PMID- 18330772
TI  - Impact of lifetime subthreshold depression and major depression before internship
      on psychopathology and quality of life in Korean interns: 6 month follow-up
      study.
AB  - OBJECTIVE: The aim of the present study was to investigate the influences of
      lifetime subthreshold depression and major depression before internship on the
      changes in psychopathology and subjective quality of life during internship.
      METHOD: A total of 151 interns at Seoul National University Hospital completed
      questionnaires including World Health Organization Quality of Life Assessment
      Instrument, Brief Version (WHOQOL-BREF), Symptom Checklist-90-Revised (SCL-90-R),
      and Beck Depression Inventory (BDI) twice at an interval of 6 months. Their
      lifetime diagnosis of depression before internship was made using the Korean
      version of Mini International Neuropsychiatric Interview (MINI), Modified Form
      for Self-Administration. RESULTS: Significant changes over time were detected
      including total score in the BDI and the Somatization, Depression, Anxiety, and
      Phobic Anxiety dimension scores in the SCL-90-R as well as all four domain scores
      in WHOQOL-BREF. In addition, in all scores except Somatization dimension score,
      group difference existed. Post-hoc comparisons showed that interns without
      lifetime depression were significantly different from those with lifetime
      subthreshold depression and those with lifetime major depression. CONCLUSIONS:
      Even a subthreshold-level, lifetime depression before internship has an adverse
      effect on the psychopathology and the subjective quality of life during
      internship. Therefore, earlier detection, monitoring, and management of this
      population would be needed throughout the intern year and beyond.

PMID- 18330773
TI  - Spinal cord injury and mental health.
AB  - OBJECTIVES: The aim of the study was to examine the mental health of adults with
      spinal cord injury living in the community. METHODS: The study was a
      representative community cross-sectional cohort self-report survey, carried out
      in adults with traumatic spinal cord injury registered on the Victorian Spinal
      Cord Injury Register and adults with non-traumatic spinal cord injury attending a
      specialist non-traumatic spinal cord injury rehabilitation clinic. Participants
      (n=443) completed a self-report survey by internet, telephone or hard copy, which
      used reliable and valid measures of depression, anxiety and stress (Depression,
      Anxiety and Stress Scale) and post-traumatic stress disorder (Impact of Events
      Scale-Revised). RESULTS: Nearly half (48.5%) of the population with spinal cord
      injury suffered mental health problems of depression (37%), anxiety (30%),
      clinical-level stress (25%) or post-traumatic stress disorder (8.4%). Overall,
      there was a twofold or more increase in the probability of emotional disorders
      compared to the general population. Of those with one mental health disorder, 60%
      also had at least one other emotional disorder, representing a substantial 56%
      increase over the general population in the probability of comorbidity of
      psychopathology. Better health and time since injury were associated with
      decreasing the risk of psychopathology. CONCLUSION: The results of the present
      study underscore the vulnerability of the population with spinal cord injury to
      emotional disorders. This study highlights the complexity of mental health
      problems experienced by many individuals with spinal cord injury living in the
      community. The delivery of mental health services to this vulnerable population
      requires recognition of comorbidity and problems of mobility, access and stigma.

PMID- 18330774
TI  - Consequences of using SF-12 and RAND-12 when examining levels of well-being and
      psychological distress.
AB  - OBJECTIVE: To explore the consequences of using the Short-Forum Health Survey (SF
      12) and the RAND-12 Health Status Inventory (RAND-12) for estimation of
      associations between its component scores and the levels of well-being and
      psychological distress. METHODS: Data from a rural community mental health survey
      of 5641 participants were analysed. Physical and mental health component scores
      of the SF-12 and RAND-12 were compared between participants with different rating
      on the Satisfaction with Life Scale and the Kessler-10. Descriptive graphical
      methods were utilized to explore the relationship between SF-12 and RAND-12
      components scores against well-being and psychological distress. Proportional
      odds model was utilized to estimate the quantitative relationship between
      component scores of the SF-12 and RAND-12 against categories of well-being and
      psychological distress. RESULTS: Both SF-12 and RAND-12 component scores were
      generally positively associated with well-being and negatively associated with
      psychological distress. Median scores were similar despite scoring techniques
      used. However, distribution of scores differed whereby the RAND-12 yielded wider
      spread of scores in measures of well-being and psychological distressed when
      compared to the SF-12. A larger proportion of participants was classified as
      having moderate and severe disability under the RAND-12 compared to the SF-12.
      CONCLUSION: It is recommended that users of the SF-12 and the RAND-12 are aware
      of the implications of utilizing either of the scoring techniques. Scoring
      techniques used should ideally be based on the theoretical basis of the study
      with consideration of the target population. Researchers may wish to use the SF
      12 if distinct uncorrelated physical and mental constructs are required and for
      studies on clinical populations. In contrast, RAND-12 should be used if
      correlated physical and mental constructs are required and if the study is on
      community or general populations.

PMID- 18330775
TI  - Maternal attitudes in pregnancy predict drinking initiation in adolescence.
AB  - OBJECTIVE: The aim of the present study was to examine whether maternal attitudes
      to pregnancy and infant caregiving predict drinking initiation in adolescence.
      METHOD: Data were used from the Mater University Study of Pregnancy, an
      Australian longitudinal study of mothers and their children from pregnancy to
      when the children were 14 years. Logistic regression analyses examined whether
      maternal attitudes to pregnancy and infant caregiving at birth and 6 months
      contributed to the prediction of drinking initiation at age 14, after controlling
      for a range of confounding covariates. RESULTS: Mother's negative feelings about
      being pregnant and not planning/wanting the pregnancy predicted adolescent
      alcohol initiation at the 14 year follow up. Negative maternal attitudes to
      infant caregiving at birth and 6 months did not predict adolescent alcohol
      initiation. CONCLUSIONS: Maternal attitudes in pregnancy are important and there
      is a need for effective perinatal interventions.

PMID- 18330776
TI  - Childhood maltreatment in patients with somatization disorder.
AB  - OBJECTIVE: There is converging evidence indicating a close association between
      trauma, particularly childhood trauma, and adult somatization, but studies using
      both structured interviews and self-report measures to assess childhood
      adversities in patients with somatization disorder are scarce. METHODS: A total
      of 28 patients (82% women, mean age=41.7+/-10.1 years) meeting DSM-IV criteria
      for somatization disorder as confirmed by the Structured Clinical Interview for
      DSM-IV, Axis I (SCID-I) underwent the Structured Trauma Interview (STI) and the
      Childhood Trauma Questionnaire (CTQ). The comparison group consisted of 28
      patients with major depression, but without a lifetime diagnosis of somatization
      disorder matched for gender and age. RESULTS: Univariate analyses of both the STI
      and the CTQ data showed that somatizing patients had been exposed to childhood
      sexual and physical abuse significantly more often than major depressive disorder
      (MDD) patients. In logistic regression analysis with somatization disorder as the
      dependent variable, sexual abuse emerged as the only significant predictor, and
      the odds of having been sexually abused were ninefold higher in patients with
      somatization disorders relative to MDD subjects (odds ratio=9.39; 95% confidence
      interval=1.73-50.96). There were no differences between somatizing and depressed
      participants with respect to other types of maltreatment. CONCLUSION: Childhood
      sexual abuse is an important factor in the multifactorial aetiopathogenesis of
      somatization disorder. Diagnostic and therapeutic implications are discussed.

PMID- 18330777
TI  - Ethnic neutropenia and clozapine.
AB  - OBJECTIVES: The aim of the present paper was to examine the concept of benign
      ethnic neutropenia and to consider the implications of ethnicity in the current
      clozapine regulatory system. METHOD: The case of a young Palestinian man who lost
      access to clozapine due to a fall in his neutrophil count, is presented herein,
      and a brief review of ethnic variations in neutrophil levels is given. RESULTS:
      This patient's clozapine was ceased, with unfortunate consequences, despite his
      having normal immune function. CONCLUSION: By using normative haematological data
      established in white populations, the Australian clozapine regulatory system
      places some non-white patients at a considerable disadvantage.

PMID- 18330778
TI  - Dual-dual action? Combining venlafaxine and mirtazapine in the treatment of
      depression.
AB  - OBJECTIVE: Venlafaxine and mirtazapine in combination are increasingly used in
      clinical practice to treat treatment-refractory depression. Putative efficacy for
      this combination of antidepressants, beyond that of monotherapy, stems from their
      synergistic actions. This paper describes a prospective case series that examined
      the efficacy of the venlafaxine-mirtazapine combination in the treatment of
      depressed patients who had failed at least one antidepressant trial. METHOD:
      Twenty-two depressed patients with major depression were treated with venlafaxine
      and mirtazapine in combination for an average of just under 8 weeks. Baseline
      ratings on the 17-item Hamilton Depression Rating Scale (HAM-D(17)), Montgomery
      Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression
      Severity Scale (CGI-S) were repeated at end-point, determined by the naturalistic
      termination of the depressive treatment episode or the discontinuation of the
      combination treatment due to adverse effects. The length of treatment until end
      point was documented for each patient. Descriptive statistics were used on the
      collated data. RESULTS: At baseline, mean scores were 28.8 (SD=3.8) for HAM
      D(17), 30.1 (SD=5.8) for MADRS, and 4.5 (SD=0.5) for CGI-S, reflecting a cohort
      at the moderate to severe end of the spectrum. At end-point, mean absolute scores
      were 10.2 (SD=4.7) for HAM-D(17), 10.8 (SD=4.6) for MADRS, and 2.3 (SD=0.6) for
      CGI-S. Mean change from baseline was 18.6 (SD=6.4) for HAM-D(17), 19.3 (SD=6.8)
      for MADRS, and 2.3 (SD=0.6) for CGI-S. Mean duration of treatment was
      approximately 8 weeks, producing a response rate of 81.8% and a remission rate of
      27.3%. Only one patient was unable to tolerate the combination although nearly
      half (10) had significant side-effects during treatment. CONCLUSION: This study
      demonstrates relatively high response and remission rates that are encouraging
      and contribute to the efficacy database for this antidepressant combination.
      Further studies using randomized controlled designs are needed.

PMID- 18330779
TI  - Water, water, everywhere, nor any drop to drink: climate change delusion.

PMID- 18330781
TI  - Putative identification of expressed genes associated with attachment of the
      zebra mussel (Dreissena polymorpha).
AB  - Because of its aggressive growth and firm attachment to substrata, the zebra
      mussel (Dreissena polymorpha) has caused severe economic and ecological problems
      since its invasion into North America. The nature and details of attachment of
      this nuisance mollusc remains largely unexplored. Byssus, a special glandular
      apparatus located at the root of the foot of the mussel produces threads and
      plates through which firm attachment of the mollusc to underwater objects takes
      place. In an attempt to better understand the adhesion mechanism of the zebra
      mussel, the suppression subtractive hybridization (SSH) assay was employed to
      produce a cDNA library with genes unique to the foot of the mussel. Analysis of
      the SSH cDNA library revealed the presence of 750 new expressed sequence tags
      (ESTs) including 304 contigs and 446 singlets. Using BLAST search, 365 zebra
      mussel ESTs showed homology to other gene sequences with putative functions. The
      putative functions of the homologues included proteins involved in byssal thread
      formation in zebra and blue mussels, exocrine gland secretion, host defence, and
      house keeping. The generated data provide, for the first time, some useful
      insights into the foot structure of the zebra mussel and its underwater adhesion.

PMID- 18330782
TI  - 90-day oral gavage toxicity study of 8-2 fluorotelomer alcohol in rats.
AB  - 8-2 fluorotelomer alcohol is a fluorinated chemical intermediate used to
      manufacture specialty polymers and surfactants. The potential subchronic toxicity
      and the reversibility of the effects of this chemical were evaluated following
      approximately 90 days of oral gavage dosing to Crl:CD(SD)IGS BR rats. A complete
      toxicological profile, including neurobehavioral assessments and hepatic beta
      oxidation, were conducted at selected intervals and a group of rats was included
      for a 90-day postdosing recovery period. Dose levels tested were 0 (control), 1,
      5, 25, and 125 mg/kg. No test-substance-related mortality occurred at any dose
      level. Rats at 125 mg/kg developed striated teeth, such that these animals were
      switched to ground chow at 77 days. No treatment-related alterations in body
      weight, food consumption, neurobehavioral parameters, or hematology/clinical
      chemistry were found. Hepatic beta-oxidation was increased in males at 125 mg/kg
      and in females at 25 and 125 mg/kg. In both males and females, plasma fluorine
      levels were increased at 125 mg/kg and urinary fluorine was elevated at > or =5
      mg/kg. Degeneration/disorganization of enamel organ ameloblast cells was observed
      at 125 mg/kg in males, but not females. Liver weight increases accompanied by
      focal hepatic necrosis were observed at both 25 and 125 mg/kg, and chronic
      progressive nephrotoxicity occurred in female rats at 125 mg/kg. With the
      exception of hepatocellular necrosis in males at 125 mg/kg and the increased
      incidence and severity of chronic progressive nephropathy in females at 125
      mg/kg, all other changes showed evidence of reversibility. The no-observed
      adverse-effect level was 5 mg/kg.

PMID- 18330783
TI  - Oral subchronic toxicity of a lipid extract from Roystonea regia fruits in mice.
AB  - D-004 is a lipid extract of royal palm (Rosytonea regia) fruits that prevents
      prostate hyperplasia induced with testosterone in rodents. Previous studies have
      shown no D-004-related toxicity in rats, but no study in mice had been reported.
      D-004 (500, 1000, and 2000 mg/kg) was evaluated in a subchronic (eight weeks)
      study in NMRI mice. No evidences of treatment-related toxicity were detected.
      Thus, body-weight gain, clinical observations, food consumption, blood
      biochemical, hematology, organ-weight ratios, and histopathological findings were
      similar in control and treated groups. This study supports that D-004 orally
      administered up to 2000 mg/kg did not induce treatment-related toxicity.

PMID- 18330784
TI  - Preclinical safety and pharmacology of Hematide, a peptidic erythropoiesis
      stimulating agent (ESA), in rats and monkeys.
AB  - The pharmacology, toxicokinetics, and safety of Hematide, a synthetic peptidic
      erythropoiesis-stimulating agent (ESA), were characterized. Hematide was given
      intravenously (0, 0.5, 5, and 50 mg/kg) weekly for five weeks with a 6- (rat) and
      12-week (monkey) recovery period. The pharmacological action of Hematide resulted
      in polycythemia. Histopathology consistent with drug-induced exaggerated
      pharmacology was observed primarily in rats. Secondary sequelae resulting from
      pronounced polycythemia was considered the cause of deaths in rats and a single
      high-dose monkey. Toxicokinetic analysis indicated prolonged exposure. In
      conclusion, Hematide is a potent ESA and the safety and efficacy profile support
      clinical development.

PMID- 18330785
TI  - Lack of alterations in thyroid hormones following exposure to polybrominated
      diphenyl ether 47 during a period of rapid brain development in mice.
AB  - Thyroid alterations have been shown to occur following exposure to polybrominated
      diphenyl ether (PBDE) mixtures, possibly indicating that disruptions in thyroid
      hormone levels may underlie behavior deficits observed in animals following
      postnatal PBDE exposure. This study determined whether acute postnatal exposure
      to PBDE-47 would alter thyroid hormones. Mice were dosed with PBDE-47 on
      postnatal day 10, and serum collected either 1, 5, or 10 days after the dose. No
      effect was observed on thyroxine and triiodothyronine levels at any age examined.
      This suggests that the neurological abnormalities reported in mice exposed to
      PBDE-47 are not due to acute changes in circulating thyroid hormones at these
      observed periods.

PMID- 18330786
TI  - Timing of implantation and closure of the palatal shelf in New Zealand white and
      Japanese white rabbits.
AB  - Two specific developmental events, namely implantation and palatal shelf closure,
      are of specific interest because they define, respectively, the beginning and the
      end of the treatment period in embryo-fetal developmental toxicity studies for
      pharmaceutical products. Thus, a detailed evaluation of the timing of
      implantation and closure of the hard palate is necessary to assure use of the
      proper exposure window in developmental toxicity studies in rabbits, the
      nonrodent species most commonly evaluated in regulatory developmental toxicology
      studies. The purpose of this study was to determine the timeline for implantation
      and closure of the hard palate in the New Zealand White rabbit, and to determine
      if this timeline differed in the Japanese White rabbit. To describe the timing of
      implantation, the uteri from does of the New Zealand White rabbit and the
      Japanese White rabbit were examined on gestation days (GDs) 5 through 8 for
      macroscopic evidence of implantation. To assess palatal shelf closure, fetuses
      were removed on GDs 17, 18, and 19 and fixed in Bouin's solution. The fetuses
      were then categorized into five stages of palatal shelf closure: open (Stage I);
      approach of the palatal shelves (Stage II); partial closure of the hard palate
      (Stage III); full closure of the hard palate (Stage IV); and full closure of the
      soft palate (Stage V). In both the New Zealand White and Japanese White rabbit
      strains, implantation was initiated on GD 6.5 and was completed on GD 7. Partial
      closure of the palate began on GD 17.5, and by GD 19, closure of the hard palate
      was completed in all fetuses, and closure of the soft palate was completed in 75
      96% of the fetuses. The timing of implantation and palatal shelf closure were
      comparable between the New Zealand White rabbit and the Japanese White rabbit.
      Therefore, treatment beginning on GD 7 and continuing until GD 19 encompasses the
      period of major organogenesis and is considered appropriate for use in
      developmental toxicity studies using either of these two strains of rabbits.

PMID- 18330787
TI  - The effects of food protector biphenyl on sister chromatid exchange, chromosome
      aberrations, and micronucleus in human lymphocytes.
AB  - The aim of this study was to determine the possible genotoxic effects of biphenyl
      (E230), which is used as an antimicrobial agent in food by using sister chromatid
      exchanges (SCEs), chromosome aberrations (CAs), and micronucleus (MN) tests in
      human peripheral lymphocytes. The human peripheral lymphocytes were treated with
      four concentrations of biphenyl (10, 30, 50, and 70 microg/mL) for 24- and 48-h
      treatment periods. In the present study, biphenyl significantly increased the
      frequency of SCEs, CAs, and the frequency of MN when compared with both untreated
      control and solvent (dimethyl sulfoxide) control. The inductions of these
      abnormalities were in a dose-dependent manner. Biphenyl was capable to induce the
      structural CAs instead of numerical CAs. Biphenyl also showed a cytotoxic effect
      by decreasing the replication index at the highest two concentrations for 48 h
      and nuclear division index at the highest two concentrations for the 24- and 48-h
      treatment periods. However, biphenyl did not affect the mitotic index (MI).

PMID- 18330788
TI  - Lack of gender-related difference in the toxicity of 2-(2'-hydroxy-3',5'-di-tert
      butylphenyl)benzotriazole in preweaning rats.
AB  - In our previous toxicity studies using young rats, we showed that an ultraviolet
      absorber, 2-(2'-hydroxy-3',5'-di-tert-butylphenyl)benzotriazole (HDBB),
      principally affected the liver, and male rats had nearly 25 times higher
      susceptibility to the toxic effects than females. In the present study, the
      toxicity of HDBB was investigated in preweaning rats. HDBB was administered by
      gavage to male and female CD(SD) rats from postnatal days 4 to 21 at a dose of 0,
      0.1, 0.5, 2.5, or 12.5 mg/kg/day. No substance-related deaths, clinical signs of
      toxicity, or body-weight changes were observed. Increased levels of albumin, AST
      and ALP in both sexes, BUN in males, and LDH in females were found at 12.5 mg/kg.
      Liver weights increased at 2.5 mg/kg and above in both sexes.
      Histopathologically, hepatocellular findings, such as nucleolar enlargement,
      anisokaryosis, increased mitosis, and/or hypertrophy, were observed at 2.5 mg/kg
      and above in both sexes. These results indicate no gender-related differences in
      the susceptibility to the toxic effects of HDBB in preweaning rats.

PMID- 18330789
TI  - Cytotoxicity, acute oral toxicity, and skin irritation of 2-ethylhexyl-2,4,5
      trimethoxycinnamate and di(2-ethylhexyl)-2,4,5-trimethoxybenzalmalonate.
AB  - Safety of two new ultraviolet (UV) filters, 2-ethylhexyl-2,4,5
      trimethoxycinnamate (E8) and 2-ethylhexyl-2,4,5-trimethoxybenzalmalonate (B8),
      has been evaluated through the human melanoma cytotoxicity test and seven-day
      acute oral toxicity studies in rats. At 2.5 mg/mL, both compounds gave similar
      cell viability to the control. LD50 values for E8 and B8 are more than 5000 and
      1000 mg/kg body weight, respectively. No significant difference in body weight
      and hematological parameters among the 0, 5, 50, 500, and 5000 mg/Kg E8-treated
      animals could be detected. Pathological examination of rat tissues collected at
      the end of the study period revealed no significant difference between the
      control and all E8-administered rats. There was no significant difference in all
      clinical blood chemistry parameters (aspartate aminotransferase, creatinine,
      blood urea nitrogen, and cholesterol), except alanine aminotransferase (ALT),
      between the control and the E8-treated animals. All ALT values were, however, in
      the normal range of SD rats. E8 showed negative results for the skin irritation
      study on human volunteers, using patch and photopatch tests. Excitation of
      respiratory signs of dypsnea in 10, 100, and 1000 mg/Kg B8-treated rats could be
      observed during 1-24 h. All groups were, however, normal during the second to the
      seventh day. Hematological parameters of the 0, 10, 100, and 1000 mg/Kg B8
      treated animals showed no significant difference. Pathological examination
      revealed no significant difference between the control and all B8-administered
      rats. However, significant differences in some clinical blood chemistry
      parameters and body weights between the control and some B8-treated animals could
      be detected. All values, however, were in the normal ranges of the SD rats.

PMID- 18330791
TI  - Laser treatments and the use of fillers. Editorial.

PMID- 18330792
TI  - Ultrastructural evidence for thermal injury to pilosebaceous units during the
      treatment of acne using photopneumatic (PPX) therapy.
AB  - BACKGROUND AND OBJECTIVE: Acne is a very prevalent skin disorder, and several
      devices, such as blue light, pulsed dye laser, diode laser, LED, RF and pulsed
      light systems, have been reported to have varying degrees of efficacy for
      treatment. Photopneumatic therapy (PPX) is a novel technology that combines
      pneumatic energy with a broadband light source to manipulate the optical
      characteristics of the skin. A vacuum suction raises target structures in the
      dermis closer to the surface of the skin prior to exposure, allowing for more
      efficient energy transmission. This study tested the hypothesis that a
      combination of pulsed light and suction would affect sebaceous plugging within
      diseased pilosebaceous apparati at a histological level, resulting in the rapid
      clearance of acne lesions. METHODS: Eight individuals were treated with PPX once
      per week for a total of five treatments. Punch biopsies of the treated areas were
      obtained just after the first exposure, just before the third exposure and
      immediately after the fifth exposure. Those specimens were examined by
      conventional and by electron microscopy for any alterations following treatment.
      RESULTS: Immediately following the first treatment, the mechanical extrusion of
      comedo contents from the infundibulum was observed histologically. One week after
      the second treatment, thermally injured bacteria as well as direct thermal injury
      to pilosebaceous apparati were observed ultrastructurally. CONCLUSION: These
      results correlate with clinical reports on decreased sebaceous gland activity
      after PPX treatment and may mechanistically give rise to the rapid regression of
      acne lesions.

PMID- 18330793
TI  - Comparison study of a long-pulse pulsed dye laser and a long-pulse pulsed
      alexandrite laser in the treatment of port wine stains.
AB  - BACKGROUND: Port wine stains (PWSs) are commonly treated by the pulsed dye laser.
      Recently, a long-pulse pulsed alexandrite laser was used to treat bulky vascular
      malformations. OBJECTIVE: In the present study, we compare the efficacy and
      complications of the long-pulse pulsed dye laser (LPPDL) and the long-pulse
      pulsed alexandrite laser (LPPAL) in the treatment of PWSs. METHODS: Eleven
      patients with Fitzpatrick skin types III-IV were enrolled in this study. One
      section of each patient's PWS was treated with LPPDL and another section was
      treated with LPPAL. The patients' PWSs were evaluated for efficacy of elimination
      of erythema and for treatment-related side effects. RESULTS: Both LPPDL and LPPAL
      treatment are effective in the treatment of PWSs. Hyperpigmentation was seen in
      two areas treated with LPPDL and in three areas treated with LPPAL.
      Hypopigmentation was seen in one area treated with LPPAL, but not in any of the
      areas treated with LPPDL. There was no scarring. CONCLUSION: LPPAL works best
      with hypertrophic, purple PWSs, while LPPDL yields better clinical improvements
      with the flat, pink PWSs. Targeting of deoxyhemoglobin, deeper penetration, and
      higher fluence may explain the effectiveness of LPPAL in purple, hypertrophic
      PWSs. However, there is a risk of dyspigmentation when using the LPPAL.

PMID- 18330794
TI  - Laser hair removal pearls.
AB  - A number of lasers and light devices are now available for the treatment of
      unwanted hair. The goal of laser hair removal is to damage stem cells in the
      bulge of the follicle through the targeting of melanin, the endogenous
      chromophore for laser and light devices utilized to remove hair. The competing
      chromophores in the skin and hair, oxyhemoglobin and water, have a decreased
      absorption between 690 nm and 1000 nm, thus making this an ideal range for laser
      and light sources. Pearls of laser hair removal are presented in this review,
      focusing on four areas of recent development: 1 treatment of blond, white and
      gray hair; 2 paradoxical hypertrichosis; 3 laser hair removal in children; and 4
      comparison of lasers and IPL. Laser and light-based technologies to remove hair
      represents one of the most exciting areas where discoveries by dermatologists
      have led to novel treatment approaches. It is likely that in the next decade,
      continued advancements in this field will bring us closer to the development of a
      more permanent and painless form of hair removal.

PMID- 18330795
TI  - Guidelines for laser hair removal.
AB  - Requests for removal of unwanted body hair are common in dermatologic and
      surgical practices. Technology continues to improve the achievement of a more
      permanent reduction through the use of lasers. Despite the increased use of
      lasers, to date, few guidelines exist in terms of how to approach laser hair
      removal. Specifically, one must understand the mechanism of hair growth and how
      lasers work to target the hair follicle. There is significant variation among
      practitioners in pre-and post-laser recommendations to patients as well as
      intervals between treatment sessions. We performed a thorough review of the
      literature in order to determine evidence for the ideal interval between
      treatment sessions and the ideal number of sessions. We also sought to establish,
      based on published reports, the recommendations for shaving, plucking, waxing or
      other hair removal methods prior to laser hair removal and the guidelines for sun
      exposure before and after laser treatments. Finally, we searched the literature
      to find out whether there are areas that should not be treated with laser hair
      removal. The evidence and recommendations in this article aim to help guide
      practitioners in their approach to laser hair removal.

PMID- 18330796
TI  - The science of hyaluronic acid dermal fillers.
AB  - BACKGROUND: The use of injectable materials for soft-tissue augmentation has been
      increasing in the United States, reflecting the introduction of new hyaluronic
      acid (HA)-based dermal fillers. HA dermal fillers vary widely in their physical
      and chemical characteristics and many variables contribute to their overall
      performance. This article explains the basic science of HA and describes how the
      physical properties of HA dermal fillers may influence clinical outcomes.
      HYALURONIC ACID: The chemical composition of disaccharide HA monomers, and how
      they form polymer chains and are crosslinked into gels for dermal fillers are
      described. HYALURONIC ACID DERMAL FILLERS: Key concepts and properties relevant
      to the production and performance of HA dermal fillers, such as the degree of
      crosslinking, gel hardness, gel consistency, viscosity, extrusion force, HA
      concentration, and extent of hydration are explained. New formulations of HA
      dermal fillers that have recently been approved by the US Food and Drug
      Administration differ from currently available HA fillers and may provide
      enhanced ease of extrusion and persistence over previous fillers. CONCLUSION:
      Knowledge of the chemical and physical blueprint of HA dermal fillers may help
      physicians in choosing the appropriate HA dermal filler for facial enhancements.
      This, together with appropriate injector training and injection experience,
      should lead to results that ultimately will benefit patients.

PMID- 18330797
TI  - Optimizing poly-L-lactic acid use.
AB  - Injectable devices are less invasive than surgical interventions for restoring
      youthful contours. Sculptra (Dermik Laboratories, Bridgewater, NJ, USA, a
      business of sanofi aventis U.S. LLC) contains poly-l-lactic acid (PLLA), which is
      thought to elicit in vivo collagen production around the injected implant,
      producing new volume gradually over time, and with effects lasting up to 2 years.
      Correct reconstitution and preparation of PLLA, as well as injection technique,
      are essential to ensure optimal outcomes and reduce adverse events. This article
      provides an overview of injectable devices, specifically focusing on PLLA in
      cosmetic application and optimal administration techniques to maximize efficacy
      and duration of effect.

PMID- 18330798
TI  - Treatment of ulcerated haemangiomas with a non-coherent pulsed light source:
      brief initial clinical report.
AB  - BACKGROUND: Ulceration is the most common complication of infantile haemangiomas
      and constitutes an authentic therapeutic challenge because of associated pain,
      infection, haemorrhage and subsequent scarring. OBJECTIVE: To report our
      experience with an intense pulsed light (IPL) system in the treatment of
      ulcerated haemangiomas. METHODS: Case 1: A 4-month-old girl, with haemangioma
      affecting the entire cutaneous surface of the left limb, developed four
      ulcerations on the inner aspect of this extremity. Two sessions with an IPL
      system using a triple pulse mode, a 570-nm lower cut-off filter and a fluence of
      38 J/cm2 were performed. Case 2: A 5-month-old girl with ulcerated labial
      haemangioma that previously failed to respond to intralesional corticoids was
      treated with an IPL system device. Three sessions using a triple pulse mode with
      a 570-nm lower cut-off filter and a fluence of 48 J/cm2 were realized. RESULTS:
      Good results were rapidly obtained after two and four sessions of IPL treatment,
      respectively. Pain was soon relieved and complete epithelization was obtained by
      between 1 and 2 months in both patients. CONCLUSION: Although our experience is
      rare, we believe that IPL devices may be an effective alternative treatment of
      ulcerated haemangiomas.

PMID- 18330799
TI  - Stevens-Johnson syndrome-induced facial scar treated by the fractional
      photothermolysis system.

PMID- 18330800
TI  - Unmanned assessment of respirator carbon dioxide levels: comparison of methods of
      measurement.
AB  - A study was performed to determine average inhaled carbon dioxide (F(I)CO2)
      concentrations of multiple respirators using unmanned test methods, and to
      compare results among test procedures to determine whether they could be used
      interchangeably. Respirator experiments were performed according to the National
      Institute for Occupational Safety and Health (NIOSH) (NF(I)CO2), standard
      European (ENF(I)CO2), and a modified method of the European test (BF(I)CO2) using
      full-facepiece air-purifying respirators and one air-purifying escape respirator.
      Bland-Altman statistics for determination of limits of agreement were applied to
      assess agreement among the various test methods. A considerable lack of agreement
      was found between NF(I)CO2 and ENF(I)CO2 methods and between BF(I)CO2 and
      NF(I)CO2 methods for average F(I)CO2. The modified EN136 method produced F(I)CO2
      averages about 0.13% to 0.23% above unmodified EN136 values, but the agreement
      between methods was generally acceptable. These results demonstrate that NIOSH
      and European unmanned test methods for determining respirator average F(I)CO2
      concentrations produce different results for like respirators. However, the
      findings suggest that the ENF(I)CO2 and BF(I)CO2 unmanned methods could be used
      interchangeably for quantifying respirator F(I)CO2 concentrations.

PMID- 18330801
TI  - Worker exposure to methanol vapors during cleaning of semiconductor wafers in a
      manufacturing setting.
AB  - An exposure simulation was conducted to characterize methanol exposure of workers
      who cleaned wafers in quality control departments within the semiconductor
      industry. Short-term (15 min) and long-term (2-4 hr) personal and area samples
      (at distances of 1 m and 3-6 m from the source) were collected during the 2-day
      simulation. On the first day, 45 mL of methanol were used per hour by a single
      worker washing wafers in a 102 m(3) room with a ventilation rate of about 10 air
      changes per hour (ACH). Virtually all methanol volatilized. To assess exposures
      under conditions associated with higher productivity, on the second day, two
      workers cleaned wafers simultaneously, together using methanol at over twice the
      rate of the first day (95 mL/hr). On this day, the ventilation rate was halved (5
      ACH). Personal concentrations on the first day averaged 60 ppm (SD = 46 ppm) and
      ranged from 10-140 ppm. On the second day, personal concentrations for both
      workers averaged 118 ppm (SD = 50 ppm; range: 64-270 ppm). Area concentrations
      measured on the first day at 1 m from the source and throughout the balance of
      the room averaged 29 ppm (SD = 19 ppm; range: 4-83 ppm) and 18 ppm (SD = 12 ppm;
      range: 3-42 ppm), respectively. As expected, area concentrations measured on the
      second day were higher than the first and averaged 73 ppm (SD = 25 ppm; range: 27
      140 ppm) at 1 meter and 48 ppm (SD = 13 ppm; range: 21-67 ppm) throughout the
      balance of the room. The results of this simulation suggest that the use of
      methanol to clean semiconductor wafers without the use of local exhaust
      ventilation and with relatively low room ventilation rates is unlikely to result
      in worker exposures exceeding the current ACGIH(R) threshold limit value of 200
      ppm. This study also confirmed prior studies suggesting that when a relatively
      volatile chemical is located within arm's length (near field), breathing zone
      concentrations will be about two- to threefold greater than the room
      concentration when the air exchange rate is 5-10 ACH.

PMID- 18330803
TI  - Osseointegrated trans-femoral amputation prostheses: prospective results of
      general and condition-specific quality of life in 18 patients at 2-year follow
      up.
AB  - This is the first report on prospective outcome for individuals treated with bone
      anchored trans-femoral amputation prostheses (OI-prostheses) using the method of
      osseointegration. The aim was to analyze general and condition-specific health
      related quality of life (HRQL) at 2-year follow-up as compared to the
      preoperative situation. The study population consists of the first 18
      consecutively treated patients (8 male/10 female, mean age 45 years) in a
      clinical investigation with amputations mainly caused by trauma and tumour. At
      inclusion the mean time since the amputation was 15 years (10 months - 33 years).
      Two self-report questionnaires were answered preoperatively and at follow-up: the
      SF-36 Health Survey (SF-36) and the Questionnaire for persons with a Transfemoral
      Amputation (Q-TFA). At follow-up 17/18 patients used the OI-prosthesis; one did
      not due to pain and loosening of the implant. Four of the scales of the SF-36
      (Physical Functioning, Role Functioning Physical, Bodily Pain and Physical
      Component Score) and all four scores of Q-TFA (Prosthetic Use, Prosthetic
      Mobility, Problems and Global Health) were statistically significantly improved
      at follow-up showing superior general physical HRQL, increased prosthetic use,
      better prosthetic mobility, fewer problems and a better global amputation
      situation. Thus, osseointegrated prostheses represent a promising development in
      the rehabilitation of individuals with transfemoral amputation and increase their
      quality of life.

PMID- 18330804
TI  - A comparative study of the physiological costs of walking in ten bilateral
      amputees.
AB  - The physiological cost of walking is greater in bilateral amputees (BA) than in
      both unilateral amputee and non-pathological gait. The aim of this study was to
      describe the physiological costs and other standard gait characteristics in a
      sample population of BA, walking at self-selected (comfortable) speeds. Amputees
      had bilateral trans-tibial, bilateral trans-femoral or trans-tibial/trans-femoral
      amputations as a result of trauma or congenital defects. All amputees wore their
      own prosthetic limbs which were either full-length prostheses or short non
      articulating pylon prostheses (SNAPPs). The results were compared with a base
      line data set collected from a non-pathological control group. It was anticipated
      that amputees with high-level amputations would walk at the slowest speeds, have
      the highest physiological costs and lowest perception of walking ability.
      However, varying walking speeds resulted in varying exercise intensities,
      exercise heart rates and perceptions of walking that could not be directly
      related to amputation levels. It is therefore concluded that bilateral amputee
      gait is complex, varied and not easily categorized.

PMID- 18330805
TI  - Monitoring of the load regime applied on the osseointegrated fixation of a trans
      femoral amputee: a tool for evidence-based practice.
AB  - This study aimed to provide a description of the continuous recording of the true
      load regime experienced during daily living by the abutment of a trans-femoral
      amputee fitted with an osseointegrated fixation. The specific objectives: (i) To
      present an apparatus and a procedure allowing recording of the load regime, and
      (ii) an example of the raw data and six performance indicators of the usage of
      the prosthesis obtained with this method. A subject was monitored for a period of
      5 hours as he went about his daily activities. The load regime was directly
      measured and recorded using a commercial transducer and data logger. The overall
      load profile presented alternative periods of variable length of inactivity (64%)
      and activity (36%), respectively. The maximum load applied on the mediolateral,
      anteroposterior and the long axes represented 21%, 21% and 120% of the body
      weight, respectively. The anteroposterior, mediolateral and long components of
      the impulse were 395 kN.s, 359 kN.s and 2,323 kN.s, respectively. The amputee
      generated a total of 2312 gait cycles of the prosthetic leg, giving an
      approximate overall cadence of 8 stride/min. Preliminary outcomes indicated that
      the proposed method was an improvement on the current techniques as it provided
      the true loading and actual usage of the prosthesis during daily living. This
      study is a stepping stone in the development of future affordable, on-board and
      user-friendly load recording systems that can be used in evidence-based practice.

PMID- 18330806
TI  - Effects of insole with toe-separator and night splint on patients with painful
      hallux valgus: a comparative study.
AB  - The objective of this study was to compare the effects of wearing an insole with
      toe separator and night splint on hallux valgus and intermetatarsal angles and
      also on the intensity of pain in patients suffering from painful hallux valgus
      deformity. Subjects in this study consisted of 30 female patients aged 19 - 45
      years (mean 27.83 +/- 8.91) who were divided into two groups. The first group
      received the insole and toe separator and the second group received night splint.
      Hallux valgus angle and intermetatarsal angle were radiographically measured
      before and after a 3-month study period. Foot pain intensity was assessed by 10
      cm Visual Analogue Scale before and after intervention. After statistical
      analysis the reduction of pain was significant in the first group (p < 0.05)
      whereas in the second group no significant difference was obtained. The hallux
      valgus angle and intermetatarsal angle decreased in both groups; however, the
      reduction was not significant. According to the results of this study, using
      night splint seems to have no effect on painful hallux valgus deformity. On the
      other hand, although the insole with toe separator significantly decreased the
      pain intensity in these patients and was a good option for pain reduction, it was
      not effective in improvement of the great toe angles.

PMID- 18330807
TI  - A comparative evaluation of the Adaptive knee and Catech knee joints: a
      preliminary study.
AB  - The Adaptive knee joint is a microprocessor-controlled prosthetic knee that
      incorporates both pneumatic and hydraulic control in one electronic unit.
      Pneumatic control is said to provide control during swing phase and the hydraulic
      control during the stance phase of the gait. This hybrid controller is triggered
      by a computer contained within the knee that responds to input from force, time
      and angle sensors. The microprocessor then selects an appropriate speed and
      stability setting. The Catech knee joint is a conventional hydraulic knee joint.
      The aim of this study was to compare the Adaptive and Catech knee joints in
      established trans-femoral amputees. The patients meeting the inclusion criteria
      were all established trans-femoral amputees using the Catech knee joint. The
      study was carried out by performing gait analysis, assessing energy requirements
      using the Physiological Cost Index (PCI) and using questionnaires. There was no
      significant benefit gained from the use of the Adaptive knee over the Catech knee
      joint in our small study group.

PMID- 18330808
TI  - Considerations for developing an evidenced-based practice in orthotics and
      prosthetics.
AB  - Evidence-based practice has become somewhat of a catchphrase over the past ten
      years. In this paper evidence-based practice is defined and its importance for
      the development of the prosthetics and orthotics profession is highlighted. The
      authors suggest that evidence-based practice needs to be prioritized within the
      profession and that a cultural change needs to be initiated which supports
      clinicians in incorporating research findings into their daily practice. In
      addition, the authors highlight the need for prosthetists/orthotists to become
      more active in generating research rather than relying on other professional
      groups to contribute to their professional body of knowledge.

PMID- 18330809
TI  - Postural correction by osteoporosis orthosis (Osteo-med): a randomized, placebo
      controlled trial.
AB  - Currently available therapeutic options for the correction of osteoporotic
      posture changes are not effective. Rigid or semi-rigid orthoses are only
      applicable in the early phase after vertebral body fractures, and the knowledge
      about the efficacy of flexible spinal orthoses is limited. Therefore, the present
      study is aimed at investigating the efficacy of a flexible spinal orthosis
      without any stabilizing components in terms of posture improvement. Forty women
      aged (65.9 +/- 8.4 years) with a proven osteoporosis (DXA < or = -2.5) were
      randomized to receive either of three treatment regimens: (i) Orthosis (Thamert
      Osteomed) with paravertebral/lumbosacral air chamber pads (as commercially
      available); (ii) The same orthosis without air chamber pads; and (iii) Placebo
      body stocking. Measurements were performed with a 3D real-time ultrasound
      topometry system (Zebris(R) CMS 70). The posture correction was substantially and
      significantly more marked in the first group (38% of the maximally possible
      intentional erection) as compared to the second (21%) and third group (13%). The
      orthosis with air chamber pads causes a clinically meaningful trunk support in
      patients with osteoporotic posture changes. Since the device contains no rigid
      stabilizing elements, the change in posture is considered to be a result of
      muscle activation due to sensomotor stimulation by the air chamber pads.

PMID- 18330810
TI  - Effect of prosthetic ankle units on the gait of persons with bilateral trans
      femoral amputations.
AB  - In able-bodied individuals, the ankle joint functions to provide shock
      absorption, aid in foot clearance during the swing phase, and provides a rocker
      mechanism during stance phase to facilitate forward progression of the body.
      Prosthetic ankles currently used by persons with lower limb amputations provide
      considerably less function than their anatomical counterparts. However, increased
      ankle motion in the sagittal plane may improve the gait of persons with lower
      limb amputations while providing a more versatile prosthesis. The primary aim of
      this study was to examine and quantify temporal-spatial, kinematic, and kinetic
      changes in the gait of four male subjects with bilateral trans-femoral
      amputations who walked with and without prosthetic ankle units. Two prosthesis
      configurations were examined: (i) Baseline with only two Seattle LightFoot2
      prosthetic feet, and (ii) with the addition of Endolite Multiflex Ankle units.
      Data from the gait analyses were compared between prosthetic configurations and
      with a control group of able-bodied subjects. The amputee subjects' freely
      selected walking speeds, 0.74 +/- 0.19 m/s for the Baseline condition and 0.81 +/
      0.15 m/s with the ankle units, were much less than that of the control subjects
      (1.35 +/- 0.10 m/s). The amputee subjects demonstrated no difference in walking
      speed, step length, cadence, or ankle, knee, and hip joint moments and powers
      between the two prosthesis configurations. Sagittal plane ankle range of motion,
      however, increased by 3-8 degrees with the addition of the prosthetic ankle
      units. Compared to the control group, following initial contact the amputee
      subjects passively increased the rate of energy storage or dissipation at the
      prosthetic ankle joint, actively increased the power generation at the hip, and
      increased the extension moment at the hip while wearing the prosthetic ankle
      configuration. The amputee subjects increased the power generation at their hips,
      possibly as compensation for the reduced rate of energy return at their
      prosthetic ankles. Results from subject questionnaires administered following the
      gait analyses revealed that the prosthetic ankle units provided more comfort
      during gait and did not increase the perceived effort to walk. The subjects also
      indicated that they preferred walking with the prosthetic ankle units compared to
      the Baseline configuration. The results of the study showed that the prosthetic
      ankle units improved sagittal plane ankle range of motion and increased the
      comfort and functionality of the amputee subjects' prostheses by restoring a
      significant portion of the ankle rocker mechanism during stance phase. Therefore,
      prosthetic ankle mechanisms should be considered a worthwhile option when
      prostheses are prescribed for persons with trans-femoral amputations.

PMID- 18330812
TI  - Introduction and summary of key clinical data.

PMID- 18330813
TI  - The contraceptive efficacy of Implanon: a review of clinical trials and marketing
      experience.
AB  - OBJECTIVES: To evaluate the contraceptive efficacy of the etonogestrel-releasing
      implant Implanon as assessed in international studies and during nine years of
      marketing experience. METHODS: The analysis included 11 international studies and
      data collected during nine years of marketing experience (1998--2007). Seven of
      these studies were noncomparative; the four other studies included the 6-rod
      levonorgestrel implant system or an intrauterine device as a comparator. All
      studies except one were of at least two years in duration, and all had
      contraceptive efficacy as the objective. Market data were provided unsolicited to
      Organon, part of Schering Plough. RESULTS: The integrated efficacy analysis
      included 923 non-breastfeeding women who were exposed to the implant for 24,100
      cycles. No in-treatment or pretreatment pregnancies were reported. Fifty
      posttreatment pregnancies were reported, six of which occurred within 14 days of
      implant removal, indicating that fertility had quickly returned. Over a nine-year
      marketing period an overall pregnancy rate of 0.049 per 100 implants sold
      (estimated Pearl Index = 0.031 based on all pregnancies reported) was calculated.
      When only counting contraceptive method failures the pregnancy rate amounts to
      0.010 per 100 implants sold (estimated Pearl Index = 0.006). CONCLUSION: Implanon
      is a highly effective and quickly reversible subdermal method of long-acting
      hormonal contraception for women. Typical use of this implant achieves a
      contraceptive protection exceeding 99%.

PMID- 18330814
TI  - The effects of Implanon on menstrual bleeding patterns.
AB  - OBJECTIVES: To evaluate an integrated analysis of bleeding patterns associated
      with use of the subdermal contraceptive implant Implanon (etonogestrel, Organon,
      part of Schering-Plough) and to provide physician guidance to optimize patient
      counselling. METHODS: Data from 11 clinical trials were reviewed (N = 923).
      Assessments included bleeding-spotting records, dysmenorrhoea, and patient
      perceived reasons for discontinuation. Bleeding patterns were analysed via
      reference period (RP) analyses. RESULTS: Implanon use was associated with the
      following bleeding irregularities: amenorrhoea (22.2%) and infrequent (33.6%),
      frequent (6.7%), and/or prolonged bleeding (17.7%). In 75% of RPs, bleeding
      spotting days were fewer than or comparable to those observed during the natural
      cycle, but they occurred at unpredictable intervals. The bleeding pattern
      experienced during the initial phase predicted future patterns for the majority
      of women. The group of women with favourable bleeding patterns during the first
      three months tended to continue with this pattern throughout the first two years
      of use, whereas the group with unfavourable initial patterns had at least a 50%
      chance that the pattern would improve. Only 11.3% of patients discontinued owing
      to bleeding irregularities, mainly because of prolonged flow and frequent
      irregular bleeding. Most women (77%) who had baseline dysmenorrhoea experienced
      complete resolution of symptoms. CONCLUSION: Implanon use is associated with an
      unpredictable bleeding pattern, which includes amenorrhoea and infrequent,
      frequent, and/or prolonged bleeding. The bleeding pattern experienced during the
      first three months is broadly predictive of future bleeding patterns for many
      women. Effective preinsertion counselling on the possible changes in bleeding
      patterns may improve continuation rates.

PMID- 18330815
TI  - Tolerability and clinical safety of Implanon.
AB  - OBJECTIVES: To evaluate the tolerability and clinical safety of the subdermal,
      long-acting hormonal contraceptive Implanon. METHODS: This integrated safety
      analysis included 11 international studies concerning Implanon (68 mg
      etonogestrel) of which 10 had a duration of at least two years. Assessments
      included reports of adverse events (AEs), reasons and rates of discontinuation,
      insertion/removal complications, and the condition of the implant site. Metabolic
      and coagulation parameters are briefly discussed to fully describe the clinical
      safety profile. RESULTS: In total 942 women were exposed to Implanon for 24,679
      cycles over the course of one to five years. The overall discontinuation rate was
      32.7%; the most frequently reported reasons for discontinuation were adverse
      events (13.9%), bleeding irregularities (10.4%), and planning pregnancy (4.1%).
      The most commonly reported drug-related AE was headache (15.3%); however,
      headache was reported in only 1.6% of women as a reason for discontinuation.
      Insertion and removal times for Implanon were short with few complications, none
      of which were major. From earlier studies it is known that treatment with
      Implanon has little effect on metabolic and coagulation parameters. CONCLUSIONS:
      Implanon is a well-tolerated and safe method of long-acting hormonal
      contraception for women.

PMID- 18330816
TI  - Heterologous assisted reproduction and kernicterus: the unlucky coincidence
      reveals an ethical dilemma.
AB  - Secrecy and anonymity related to heterologous assisted reproduction may hide
      basic newborn data to neonatologists. Secrecy and anonymity are discussed in view
      of their possible consequences on relational dynamics and on developmental
      psychology. Nevertheless, they can also involve the offspring's genetic status
      regarding inheritable diseases. International guidelines have been recently
      published on this topic. Because no guidelines are 'ideal' unfortunate and
      possibly dramatic consequences can occur. We aimed to embark on a debate about
      this matter starting with a real clinical experience. In our case a rarely fatal
      but widespread disease, together with the lack of knowledge about parental status
      led, in a fast succession of clinical events, to the unavoidable insurgence of
      kernicterus.

PMID- 18330817
TI  - Medroxyprogesterone acetate modulates the immune response in the uterus, cervix
      and placenta in a mouse model of preterm birth.
AB  - OBJECTIVE: These studies sought to determine whether a progestational agent,
      specifically medroxyprogesterone acetate (MPA) prevents inflammation-induced
      preterm birth, in a mouse model, through modulation of the host immune response.
      STUDY DESIGN: Using an established mouse model of inflammation-induced preterm
      birth, the activation of the immune response in maternal serum, uterus, cervix
      and placenta was assessed. In addition, the ability of MPA to modulate this
      response was investigated. Message RNA and protein expression were assessed by
      quantitative PCR and ELISAs respectively. RESULTS: Intrauterine inflammation
      promotes a significant up-regulation of both TH1 and TH2 mediators in all tissues
      studies though the response is divergent by time and tissue studied. MPA
      significantly differentially regulates this immune response in the uterus, cervix
      and placenta. CONCLUSIONS: In the setting of inflammation-induced preterm birth,
      the host immune response is activated and not limited to a traditional TH1 bias.
      The ability of MPA to modulate the immune response may be a critical mechanism by
      which progestins prevent preterm birth.

PMID- 18330818
TI  - Intrapartum fetal ECG and diabetes.
AB  - AIM: The objective of this study was to determine the prevalence and types of ST
      segment changes of the fetal electrocardiogram (FECG) during labour in term
      fetuses born to mothers with diabetes mellitus (DM) or gestational diabetes.
      METHODS: This was a retrospective case-control study involving populations from
      two multi centre trials: the Swedish Randomized Control Trial and the European
      Union ST-analysis (EU-STAN) trial. ST-segment changes were assessed in 104/309
      cases and 207/468 controls from the Swedish and EU-STAN trials, respectively.
      RESULTS: ST depression was present on the FECG in 22.1% of fetuses of mothers
      with DM compared to 12% of controls OR = 2.6, 95% CI = 1.4-4.7, p = 0.002 after
      adjusting for trial, birth weight, and nulliparity. ST elevation was present in
      47.1% of DM patients and 41.2% of controls (OR = 1.4, 95% CI = 0.9-2.3, p =
      0.18). CONCLUSION: ST depression on the FECG was significantly more prevalent in
      the fetuses of mothers with DM, probably not indicating hypoxia but an altered
      ability of the myocardium to respond to the stress of labour. Further studies
      into the mechanism of fetal compromise during diabetic labour, are required.

PMID- 18330819
TI  - Quitting smoking is perceived to have an effect on somatic health among pregnant
      and non-pregnant women.
AB  - OBJECTIVE: To examine the association of pregnancy and intent to quit smoking
      with perception of the somatic health risk of smoking and the effect on risk of
      quitting smoking. METHODS: Pregnant and non-pregnant women, intending and not
      intending to quit smoking, (n = 80) over a two-week period rated the probability
      for smoking-related health consequences to occur, given both conditions of not
      quitting smoking and of quitting smoking. RESULTS: Groups were the determining
      variable accounting for differences in risk perception. For pregnant women who
      did not intend to quit smoking, the estimated probability for the consequences to
      occur was generally low given the condition of continuing to smoke. There was no
      effect for time. The estimated effect of quitting smoking was statistically
      significant. CONCLUSIONS: Future campaigns need to integrate risk information so
      that it can be grounded cognitively in order to increase the personal
      responsibility that women take for their own health and the health of the fetus.

PMID- 18330820
TI  - Myometrial thickness according to uterine site, gestational age and prior
      cesarean delivery.
AB  - OBJECTIVE: To evaluate the myometrial thickness (MT) of multiple uterine sites
      during all three trimesters of pregnancy in an attempt to identify anticipated
      myometrial thickness in each trimester for these sites. METHODS: In this
      prospective cross sectional study, MT was evaluated by ultrasound in women with
      viable singleton pregnancies. Women with suspected abruption, accreta, previa,
      fibroids, uterine and fetal anomalies, abnormal fluid volume, labor were
      excluded. MT was measured at the fundus, anterior wall (AW), posterior wall (PW),
      right and left side walls, lower uterine segment (LUS) and under the placenta.
      The cohort was divided to determine differences in MT at each site in each
      trimester (TRI). Differences in MT between sites were assessed. RESULTS: One
      hundred and seventy five women underwent ultrasound by a single observer. There
      were 25 1st, 100 2nd and 50 3rd TRI scans at mean (SD) gestations of 11.0 (1.9),
      21.5 (3.6) and 34.1 (3.0) weeks, respectively. Women were 37% African American,
      72% government insured, 39.4% nulliparous. A total of 13% of women had a prior
      cesarean. MT of the fundus was less than AW, PW, right and left side walls (p <
      0.05 each). For all sites, MT was less in 2nd compared with 1st TRI (p < 0.0001
      each). This was most evident with fundal and LUS MT (35% less each). There was no
      difference in MT between 2nd and 3rd TRI. Fundal, AW, left side wall,
      subplacental and LUS MT were greater in parous women (p < 0.05 each). With
      anterior placentation, AW MT was less than when the placenta was implanted
      elsewhere (6.6 vs 7.4 mm, p = 0.008). This was not found with fundal or posterior
      placentas. The LUS MT was not less with prior cesarean (6.1 vs 6.0 mm, p = 0.84).
      CONCLUSION: Myometrial thickness of all uterine sites is less in 2nd and 3rd
      trimesters compared with the 1st trimester. Fundal MT is less than other upper
      segment MT in the 2nd and 3rd trimesters. LUS MT is not less with prior cesarean.

PMID- 18330821
TI  - Early activation of the hypothalamic-pituitary-adrenal-axis in very-low-birth
      weight infants with small thymus at birth.
AB  - BACKGROUND: An acute thymic involution in human fetuses and newborns has been
      described in very-low-birth-weight (VLBW) infants with histological
      chorioamnionitis. However, the mechanisms of thymic involution remain to be
      clarified. Here, we tested the hypothesis that an activation of the hypothalamic
      pituitary-adrenal (HPA) axis occurs in VLBW infants with acute thymic involution
      at birth. METHODS: A total of 180 randomly selected VLBW newborns (28.8 +/- 3.15
      wk gestation; 1093 +/- 305 g) entered the study. Thymic size was measured on
      standard chest radiographs at birth, and expressed as the ratio between the
      transverse diameter of the cardiothymic image at the level of the carina (CT) and
      that of the thorax (T). CT/T < 0.28 was considered to indicate a small thymic
      size. Plasma cortisol and adrenocorticotropic hormone (ACTH) concentrations were
      determined on days 1 (d-1) and 7 (d-7), and at 1 month (mo-1). Results. A total
      of 66 (36.7%) newborns had CT/T < 0.28. Infants with small thymus had
      significantly increased cortisol on d-1 ( approximately 5.2-folds) [median: 18.95
      (95% CI: 11.20-39.4) microg/dl vs. 3.66 (1.94-6.82) microg/dl, p < 0.0001)] and d
      7( approximately 1.7-folds) [12.0 (4.39-22.97) microg/dl vs. 7.8 (3.63-12.8)
      microg/dl, p = 0.0384)], as compared with those with normal thymic size, together
      with higher adrenocorticotropic hormone (ACTH) concentrations on d-1 (
      approximately 1.9-folds) [28 (15.6-61.07) pg/ml vs. 14.9 (9.0-23.42) pg/ml, p =
      0.0005)], while no significant differences for cortisol at mo-1 or ACTH
      concentrations on d-7 and mo-1 were evidenced (p > 0.50). From a multivariate
      logistic regression analysis, a small thymus at birth was a significant
      independent predictor of plasma cortisol concentrations in the top-quartile (OR =
      14.4; 95% CI: 6.079-34.11), and plasma ACTH concentrations in the top-quartile
      (OR = 4.40 (95% CI: 1.99-9.74) on d-1 (results adjusted for variables significant
      at univariate analysis). CONCLUSIONS: Our data indicated the presence of a
      previously unrecognized, early activation of the HPA axis in VLBW newborns with a
      small thymus at birth.

PMID- 18330822
TI  - An increased risk for non allo-immunization related intrauterine fetal death in
      RhD-negative patients.
AB  - OBJECTIVE: To investigate immediate perinatal outcome of RhD-negative patients
      carrying RhD-positive fetuses who received antenatal Rh immunoglobulin for the
      prevention of RhD-mediated hemolytic disease of the fetus and newborn. METHODS: A
      retrospective population-based analysis was conducted comparing pregnancies of
      all RhD-negative women who received antenatal Rh immunoglobulin prophylaxis (anti
      D), to RhD-positive parturients, during the years 1988-2003. All women were RhD
      negative without evidence of RhD sensitization. Patients received anti-D during
      the 28-30th week of pregnancy, and an additional dosage within 72 hours following
      delivery after confirmation of the newborn's RhD status. RESULTS: Of 145,437
      deliveries during the study period, 6.8% were of RhD-negative women (n = 9961).
      Perinatal mortality rate was significantly higher among the RhD-negative women
      who received antenatal prophylaxis rhesus immunoglobulin as compared with the
      controls (17/1000 vs. 12/1000, OR = 1.3, 95%CI 1.2-1.6; p < 0.001). This higher
      mortality rate was related to a higher rate of intrauterine fetal demise (IUFD)
      (10/1000 vs. 6/1000, OR = 1.5, 95%CI 1.2-1.9; p < 0.001). The association
      remained significant after controlling for RhD isoimmunization leading to hydrops
      fetalis, using the Mantel-Haenszel technique (weighted OR = 1.3; 95% CI 1.1-1.5;
      p = 0.001). The rate of RhD isoimmunization was 0.6% (n = 58). Using a
      multivariable analysis with IUFD as the outcome variable, controlling for known
      confounders for fetal demise, RhD-negative status was an independent risk factor
      for IUFD. CONCLUSION: RhD-negative women carrying RhD-positive newborns are at an
      increased risk for IUFD despite Rh immunoprophylaxis.

PMID- 18330823
TI  - Pregnancy, obstetric and neonatal outcome after assisted reproduction in
      Nigerians.
AB  - PURPOSE: To evaluate the pregnancy, obstetric and neonatal outcome after assisted
      reproduction in Nigerians. METHODS: Case control study of all confirmed
      pregnancies following assisted reproduction managed at the Havana Specialist
      Hospital (HSH), Lagos over a 7 year period. RESULTS: Adverse obstetric and
      neonatal outcome occurred in 30.8% of pregnancy following assisted reproduction
      compared to 12.6% in spontaneously conceived pregnancy (p = 0.0003). Multiple
      pregnancy (<0.001), preterm delivery (p < 0.000), placenta praevia (0.00002),
      antenatal admission (0.02), early pregnancy bleeding (0.04), miscarriage (0.001)
      and caesarean delivery (<0.001) were significantly commoner in the assisted
      reproduction group. After adjustment for confounding variables, preterm delivery
      (OR: 5.95), miscarriage (OR: 5.84), multiple pregnancy (OR: 4.58), placenta
      praevia (OR: 4.13), caesarean delivery (OR: 3.57), early pregnancy bleeding (OR:
      2.18) and antenatal admission (OR: 2.01) retained their significance. CONCLUSION:
      This study has provided the first evidence from our part of the world showing
      that assisted pregnancy is associated with poorer obstetric outcome when compared
      with spontaneously conceived pregnancy.

PMID- 18330824
TI  - Whole-genome microarray and targeted analysis of angiogenesis-regulating gene
      expression (ENG, FLT1, VEGF, PlGF) in placentas from pre-eclamptic and small-for
      gestational-age pregnancies.
AB  - OBJECTIVE: To compare the placental pathology associated with pre-eclampsia (PE)
      and/or fetal growth restriction, the transcriptomes of placental tissues from PE
      and small-for-gestational-age (SGA) pregnancies were explored. In addition, a
      targeted analysis of angiogenesis-regulating gene expression was performed.
      METHODS: Whole-genome microarray analysis was performed on placental tissue from
      gestational age-matched PE (n = 10), SGA (n = 8) and PE + SGA (n = 10)
      pregnancies. The expression of genes regulating angiogenesis (endoglin (ENG), fms
      related tyrosine kinase 1 (FLT1), vascular endothelial growth factor (VEGF) and
      placental growth factor (PlGF)) was analyzed by quantitative real time reverse
      transcriptase polymerase chain reaction (qRT-PCR). RESULTS: Microarray analysis
      did not reveal any significant differences between groups. However, an increased
      expression of ENG and FLT1 was detected by qRT-PCR in the PE + SGA group.
      CONCLUSIONS: The placental transcriptome did not differ between groups, although
      an increased anti-angiogenic gene expression in PE + SGA was observed with qRT
      PCR analysis. Based on this, we conclude that although microarray technology may
      represent a powerful tool in generating new hypothesis in complex fields, it may
      not be sensitive enough to detect subtle changes in gene expression.

PMID- 18330825
TI  - Duration of the active phase of labor in twin pregnancies.

PMID- 18330826
TI  - High perinatal mortality in Darfur, Sudan.

PMID- 18330827
TI  - Allergic contact dermatitis with a fertilizer containing hydrogen cyanamide
      (Dormex).
AB  - Cyanamide is a chemical substance used in the treatment of chronic alcoholism as
      well in agriculture as a fertilizer. We report the case of a 28-year-old healthy
      non-atopic man that developed a severe skin eruption after the accidental
      penetration of a small amount of Dormex (a plant growth regulator containing
      cyanamide) through the patient's gloves. Patch tests revealed positive reactions
      to Dormex 1% pet. and cyanamide at a dilution of 0.1% pet. and 1% pet. We discuss
      the causes of sensitization in a patients that regularly used protective measures
      during anti-parasites treatments.

PMID- 18330828
TI  - Severe cutaneous adverse drug reaction to leflunomide: a report of two cases.
AB  - The purpose of this study was to report severe cutaneous reactions in two
      patients related with leflunomide. A 13-year-old girl was treated with
      leflunomide for systemic lupus erythematosus. Three months later a progressive
      generalized blistering formation occurred and epidermolysis appeared on her skin.
      Methylprednisolone pulse therapy and intravenous immunoglobulin were used to
      control the severe cutaneous reactions. The patient recovered within 18 days.
      Another case is a 63-year-old woman who was treated with leflunomide for primary
      Sjogren's syndrome. Four months later widespread prunosus skin rash appeared on
      her skin. Methylprednisolone pulse therapy was also used to control the severe
      cutaneous reactions. The patient was recovered 11 days later. Our report suggests
      that an association between leflunomide intake and severe cutaneous reactions in
      rheumatic disease patients should be considered.

PMID- 18330829
TI  - Evaluation of treatments for cyanoacrylate eyelash adhesion using an in-vitro
      model.
AB  - We evaluated 4 suggested treatments for cyanoacrylate (CA) eyelash adhesion.
      Nylon paintbrushes were used to simulate human eyelashes. Brushes were treated
      with one drop of CA and allowed to dry. The brushes were randomly assigned to one
      of 6 treatment groups: Bacitracin, water, K-Y Jelly, baby shampoo, acetone
      (+control), and no treatment (-control). Two blinded investigators independently
      rated each brush to determine if the treatment decreased the adhesion of the
      bristles. Six brushes were assessed for each therapy. No treatment option was
      superior to control, and all treatments except acetone had no effect on bristle
      adherence. Our results suggest these treatments are unlikely to be clinically
      useful for removing CA from eyelashes.

PMID- 18330830
TI  - Mystery of the disappearing allergen: published allergens rarely seen again.
AB  - Patch testing is an important tool in the diagnosis of allergic contact
      dermatitis. Although this technique can be accurate, occasionally the results may
      be inconclusive. A previously positive result to an allergen may become negative
      upon repeat testing, and this may complicate the process of achieving a
      definitive diagnosis. There are some potential explanations for such
      inconsistencies, including the Excited Skin Syndrome, irritant reactions, a need
      to repeat the diagnostic algorithm, "rogue" reactions, and "contact allergy."
      These explanations should be taken into account when interpreting these results.
      However, further knowledge is needed to solve the mystery of an allergen that
      subsequently disappears.

PMID- 18330831
TI  - Impact of textiles on formation and prevention of skin lesions and bedsores.
AB  - A bedsore or pressure ulcer is an area of localized damage to the skin and
      underlying tissue caused by pressure, shear, friction, or a combination of these
      factors. In countries with a large geriatric population like Canada, this
      healthcare threat presents a significant risk to hospitalized patients, imposing
      huge cost on both treatment and care for patients. The role textiles play in the
      formation and prevention of pressure ulcers is understudied. The fact remains,
      textiles, such as clothing and bedding, have a considerable influence on factors,
      such as pressure, shear/friction, and skin hydration, which contribute to skin
      ulceration. Our work is a pilot study to investigate the role of textile products
      in the formation and prevention of bedsores. This study began with a survey study
      at a local long-term care facility, collecting information about incidences of
      bedsores and the physical conditions of residents. Information was also collected
      about the textile products that have been used by the residents. Correlations
      were established between these products and the incidence/severity of bedsores.
      Immobility of residents was determined to be a significant factor of causing skin
      lesions and pressure ulcers. Immobility of residents contributes to a prolonged
      interaction between skin and fabrics and might increase the chances of skin
      lesions or bedsores.

PMID- 18330832
TI  - Percutaneous toxicity of anticoagulant warfarin in rats.
AB  - Percutaneous toxicity of anticoagulant rodenticides is usually manifested by
      coagulopathy and/or fatal outcome. There are, however, virtually no data on other
      biological effects of this class of pesticides that gain access into the organism
      via skin. In this study, percutaneous toxicity of epicutaneously applied warfarin
      was evaluated by measuring changes in peripheral blood granulocytes in rats.
      Application of 10 mug (0.05 mg/kg) or 100 mug (0.5 mg/kg) of warfarin (WF) for 3
      consecutive days resulted in an increase in prothrombin time, documenting the
      access of warfarin to systemic circulation. Application of warfarin led to an
      increase in relative numbers of granulocytes at higher dose, whereas both doses
      resulted in increased metabolical viability, evaluated by 3-(4, 5-dimethyl-2
      thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Higher
      warfarin dose resulted in both granulocyte activation and priming (evaluated by
      cytochemical nitroblue tetrazolium, NBT, reduction assay of respiratory burst),
      whereas only a tendency toward activation was noted at lower WF dose. Soluble
      mediators from the circulation seem responsible for the observed effects, as
      exogenous plasma from WF-treated animals stimulated NBT reduction by isologous or
      naive granulocytes. Data presented in this study are relevant for the recognition
      of biological effects, other than those affecting hemostasis, of anticoagulant
      rodenticides that gain access to systemic circulation through the skin.

PMID- 18330833
TI  - The role of NAD+ depletion in the mechanism of sulfur mustard-induced metabolic
      injury.
AB  - Results of our previous studies on the chemical warfare agent sulfur mustard
      (2,2'-dichlorodiethyl sulfide) suggested that mustard-induced inhibition of
      glycolysis is not solely a function of NAD+ depletion. To define the role of NAD+
      in mustard-induced metabolic injury, we examined the effects of mustard+/
      niacinamide on energy metabolism in cultured human keratinocytes. Sulfur mustard
      caused concentration-dependent decreases in viable cell number and ATP content at
      24 hours, but not earlier, and time- and concentration-dependent glycolytic
      inhibition and NAD+ depletion as early as 4 hours. Niacinamide partially
      protected NAD+ levels at all time points, but did not prevent adverse effects on
      glycolysis, intracellular ATP, or viable cell number. These results support our
      earlier conclusions and suggest that sulfur mustard may inhibit glycolysis
      directly.

PMID- 18330834
TI  - Drug-induced psoriasis: results from pharmacovigilance tools under investigation.

PMID- 18330835
TI  - Prediction of short-term neurological outcome in full-term neonates with hypoxic
      ischaemic encephalopathy based on combined use of electroencephalogram and neuro
      imaging.
AB  - BACKGROUND: In infants with hypoxic-ischaemic encephalopathy (HIE), prediction of
      the prognosis is based on clinical, neuro-imaging and neurophysiological
      parameters. METHODS: EEG, cranial ultrasound, MRI and follow-up findings of 23
      infants (GA 35-42 weeks) with HIE were studied retrospectively to assess 1) the
      contribution of ultrasound, MRI and EEG in predicting outcome, 2) the accuracy of
      ultrasound as compared to MRI, and 3) whether patterns of brain damage and EEG
      findings are associated. RESULTS: An abnormal EEG background pattern was highly
      predictive of adverse outcome [positive predictive value (PPV) 0.88]. If combined
      with diffuse white and deep and/or cortical grey matter changes on ultrasound or
      MRI, the PPV increased to 1.00. Abnormal neuro-imaging findings were also highly
      predictive of adverse outcome. Abnormal signal intensity in the posterior limb of
      the internal capsule, and diffuse cortical grey matter damage were associated
      with adverse outcome. MRI showed deep grey matter changes more frequently than
      ultrasound. Severely abnormal neuro-imaging findings were always associated with
      abnormal EEG background pattern. CONCLUSIONS: Both early EEG and neuro-imaging
      findings are predictive of outcome in infants with HIE. The predictive value of
      EEG is strengthened by neuro-imaging.

PMID- 18330836
TI  - Axonal degeneration induced by intraneural injection of Campylobacter jejuni
      antiserum containing high titer anti-GM1 antibody.
AB  - Ganglioside-like structures in CAMPYLOBACTER JEJUNI ( C. JEJUNI)
      lipooligosaccharide (LOS) can induce antiganglioside antibodies, which might
      cause nerve damage. In this study, we injected the following three antisera
      directly into the sciatic nerve of guinea pigs, to investigate the role of anti
      glycolipids antibody in inducing neural injury: (i) the wild strain antiserum, a
      mixture of the sera obtained from the guinea pigs immunized with C. JEJUNI wild
      type strain (HS:19) that had a high titer anti-GM1 IgG antibody (range: 800
      6,400; median: 2,400) and a high titer anti-LOS IgG antibody; (ii) the GALE
      mutant antiserum, a mixture of the sera obtained from the guinea pigs immunized
      with the GALE mutant strain that had only a high titer anti-LOS IgG antibody but
      no anti-GM1 antibody; and (iii) the control antiserum, a mixture of the sera
      obtained from the guinea pigs immunized with Freund's complete adjuvant alone
      which had no anti-GM1 or anti-LOS IgG antibody. Pathological examinations showed
      that the wild strain C. JEJUNI antiserum produced axonal degeneration in sciatic
      nerves. Demyelination was rare, and no inflammatory cells were present. The
      pathological features are consistent with those seen in human patients with
      axonal GBS. No such changes were observed in nerves injected with the GALE mutant
      antiserum. The experiment showed that passive transfer of serum containing high
      titer GM1 antibody caused axonal degeneration of peripheral nerves. The result,
      which reproduced our previous findings in an active immunization study, therefore
      further confirmed the critical role of the anti-glycolipid antibody in the
      induction of neuropathy.

PMID- 18330837
TI  - Application of a scorable neurological examination to near-term infants:
      longitudinal data.
AB  - The aim of this study was to follow the evolution of neurological findings in a
      cohort of near-term infants born between 35 and 37 weeks. A total of 448 infants
      born between 35 and 36.9 weeks gestational age with normal cranial ultrasonograms
      or only minor abnormalities, were studied using the Hammersmith Infant
      Neurological Examination, at 6, 9 and 12 months (corrected for prematurity). Our
      results showed that while some items such as cranial nerve and movements showed
      minimal changes over time, other items mainly related to "tone", "posture" and
      "reflexes" showed progressive maturation. There was no significant difference
      between the infants born at 35 and 36 weeks gestation. When compared to term
      infants assessed at the same age intervals, our cohort showed a wider variability
      of scores. Mean and 10 (th) percentile for global scores were lower than those
      reported for term infants suggesting that when assessing infants born at 35 and
      36 weeks the optimality scores used for infants born full-term should not be used
      as normative data. Our results, providing longitudinal data in near-term infants
      without brain lesions, can be used as a reference in both clinical and research
      setting to monitor early neurological signs in those children.

PMID- 18330838
TI  - Pediatric Scoliosis Surgery - the association between preoperative risk factors
      and postoperative complications with emphasis on cerebral palsy children.
AB  - Scoliosis repair surgery is a common procedure. Our study's first goal was to
      compare pre- and postoperative parameters between the cerebral palsy (CP) and
      idiopathic scoliosis (IS) children. The second goal was to establish possible
      associations between preoperative parameters that could predict the outcome of
      spinal surgery and the incidence of early postoperative complications. A
      retrospective record review of all children who underwent scoliosis operative
      surgery between 1998 and 2007 was conducted. Of the 141 children included, 21
      were CP and 120 were IS. The CP children attended surgery with significantly
      lower weight and pulmonary reserves and had larger curves and fusions compared to
      the IS children. CP children had a significantly higher rate of major
      complications, especially pulmonary and neurological, and a higher rate of
      delayed extubations. In addition, young age at surgery and posterior spinal
      fusion correlated with a more favorable immediate postoperative prognosis among
      the IS population. CP children attended surgery in worse physical condition and
      in turn had a poorer immediate and short-term postoperative prognosis than IS
      children. Young age at surgery and posterior fusions revealed protective
      characteristics among the IS population.

PMID- 18330839
TI  - Relation of spasms and myoclonus to suppression-burst on EEG in epileptic
      encephalopathy in early infancy.
AB  - PURPOSE: This study was intended to clarify the relation between spasms in series
      and a suppression-burst (SB) EEG pattern which have a common nature of repetitive
      bursting activity in epileptic encephalopathy in early infancy. METHODS: The
      ictal EEG traces of spasms were temporally compressed and expanded to study the
      beginning and ending phases of series along with their spectral analysis in two
      patients with Ohtahara syndrome (OS) and one with early myoclonic encephalopathy
      (EME). The EEG bursts associated with myoclonus were also investigated. RESULTS:
      A mutual transition was indicated between the ictal activity of spasms and the
      bursts in the peri-series SB on EEG. Gamma rhythm was detected in common in the
      ictal activity and the peri-series and interictal bursts on EEG, and also in the
      bursts with myoclonus. CONCLUSION: The relation between the ictal activity of
      spasms and SB on EEG was shown to be close. The generative mechanisms of spasms
      and myoclonus might be linked to the bursting tendency intrinsic to immature
      brain function.

PMID- 18330840
TI  - Congenital gingival hyperplasia in a neonate with foetal valproate syndrome.
AB  - There are several causes of gingival hyperplasia and one of the most well-known
      is drug-induced gingival enlargement. Nevertheless, causes of congenital gingival
      enlargement include only hereditary and metabolic disorders. Only one case of
      drug-induced congenital gingival hyperplasia has been reported. We present the
      second neonate with gingival hyperplasia in the context of foetal valproate
      syndrome and review the literature.

PMID- 18330841
TI  - Focal epilepsy resulting from a de novo SCN1A mutation.
AB  - We found a DE NOVO missense mutation of the gene encoding the alpha1 subunit of
      the neuro-nal voltage-gated sodium channel, SCN1A, in a patient with repetitive
      focal seizures. At 5 months of age, the patient had a first seizure characterized
      by loss of consciousness and clonic convulsions in the left hand followed by
      secondary generalization lasting for 20 minutes in association with pyrexia.
      Although valproate was administered, she has had generalized seizures every
      month, mostly in association with elevated body temperature. Since 32 months of
      age, she also had a different type of seizure characterized by a fearful response
      followed by decreased consciousness, pallor, and salivation. Myoclonia or
      atypical absence seizures have never been observed until the last follow-up at 42
      months of age. Genetic analysis showed a heterozygous missense mutation
      (c.5311A>T: I1771F) in the patient, which was not detected in her parents.

PMID- 18330842
TI  - Detection of autoantibodies against NMDA-type glutamate receptor in a patient
      with recurrent optic neuritis and transient cerebral lesions.
AB  - We describe the case of a Japanese girl with recurrent optic neuritis and
      transient cerebral lesions. Antibodies against N-methyl-d-aspartate (NMDA)-type
      glutamate receptors were detected in both serum and cerebrospinal fluid. Results
      of this case study suggest that the development of autoantibodies against NMDA
      type glutamate receptors may play a role in the pathogenesis of central nervous
      system demyelinating diseases.

PMID- 18330843
TI  - Association of HAX1 deficiency with neurological disorder.
AB  - Severe congenital neutropenia (SCN) is a rare, heterogeneous, primary
      immunodeficiency disorder characterized by early onset of severe bacterial
      infections. We here describe a case of SCN associating neutropenia and
      neurodevelopmental delay. The girl was well until the age of 9 months, when she
      suffered from an episode of convulsion. Subsequently, she developed several
      episodes of superficial abscesses, oral ulcers and otitis media. Further work-up
      revealed severe congenital neutropenia caused by a homozygous mutation (R86X) in
      the antiapoptotic molecule HAX1. She also suffered from psychomotor retardation
      and recurrent seizures. This case illustrates that HAX1 deficiency may be
      associated with a neurological phenotype.

PMID- 18330844
TI  - Conversion of a normal MRI into an MRI showing a cystic leukoencephalopathy is
      not a known feature of vanishing white matter.

PMID- 18330846
TI  - [A retrospective study of the effectiveness of lamotrigine in monotherapy for the
      treatment of epileptic seizures. The ERELMO study].
AB  - INTRODUCTION: The efficacy and tolerability of lamotrigine (LTG) in monotherapy
      and in combination therapy have been demonstrated in clinical trials. The aim of
      the ERELMO study was to retrospectively evaluate the effectiveness and safety of
      LTG, as monotherapy in the control of epileptic seizures in routine clinical
      practice in Spain. PATIENTS AND METHODS: 446 clinical records were selected of
      patients with LTG treatment in the twelve months previously to the beginning of
      the study. The main endpoints retrospectively analyzed were effectiveness
      (percentage of patients with 50% or greater reduction in seizure frequency,
      improvement in seizure control, percentage of patients remaining-seizure free at
      2, 6 and 12 months of LTG monotherapy), and safety (adverse event profile
      reported and treatment withdrawal). RESULTS: The mean age was 41 years old, 57.8%
      were women. LTG monotherapy treatment (mean maintenance dose was 217.2 mg/day)
      reduced mean seizure frequency as compared with the basal condition at different
      study time points (2, 6, 12 months; p < 0.0001). At the end of the study 77% of
      the patients were seizure free. Loss of treatment effectiveness was shown in 8.5%
      of patients. Adverse reactions were reported by 15% of patients, the most
      frequent being insomnia, somnolence, headache and rash. At the end of the study,
      88.8% patients were still receiving LTG monotherapy. CONCLUSIONS: The present
      study supports the use of LTG monotherapy due to its effectiveness and good
      tolerability to promote treatment compliance in usual clinical conditions in
      patients with epilepsy.

PMID- 18330847
TI  - How do copper enzymes hydroxylate aliphatic substrates? Recent insights from the
      chemistry of model systems.

PMID- 18330848
TI  - Sustained liver-specific transgene expression from the albumin promoter in mice
      following hydrodynamic plasmid DNA delivery.
AB  - BACKGROUND: To properly study gene expression in vivo, often long-term expression
      is desired. Previous studies using plasmid DNA (pDNA) vectors have typically
      resulted in short-term expression. Here, we evaluated combinations of the albumin
      promoter with different enhancers and untranslated regions for liver-specific
      expression in mice. METHODS: A series of pDNA secreted alkaline phosphatase
      (SEAP) reporter gene expression vectors was constructed using the albumin
      promoter and various other expression cassette elements. Each was evaluated for
      level and duration of SEAP expression in mice following hydrodynamic tail vein
      delivery. RESULTS: Sustained liver expression was obtained from vectors combining
      the albumin promoter with an albumin 3' untranslated region (3'UTR). The level of
      expression was increased by inclusion of enhancers and a 5' intron. The optimal
      expression vector consisted of the albumin promoter combined with an alpha
      fetoprotein MERII enhancer, 5' intron from the factor IX gene, and the 3'UTR from
      the albumin gene including intron 14. With this vector, SEAP reporter gene
      expression levels remained high for 1 year, at levels comparable to those
      obtained from the cytomegalovirus (CMV) promoter on day 1. Expression of human
      apolipoprotein E3 (hApoE) in ApoE knockout mice provided a dose-dependent
      correction of their hypercholesterolemia. CONCLUSIONS: Liver-specific sustained
      transgene expression can be obtained at very high levels from optimized pDNA
      vectors, without the use of integration systems. Such vectors will further
      facilitate biological studies of genes in vivo and may find application in gene
      therapy.

PMID- 18330849
TI  - Directed evolution of galactose oxidase: generation of enantioselective secondary
      alcohol oxidases.

PMID- 18330850
TI  - Enzymatic glycosylation of peptide arrays on gold surfaces.

PMID- 18330851
TI  - LOV1 protein from Chlamydomonas reinhardtii is a template for the photoadduct
      formation of FMN and methylmercaptan.

PMID- 18330852
TI  - Fusion peptides and transmembrane domains of fusion proteins are characterized by
      different but specific structural properties.
AB  - Membrane fusion is essential for many biological processes. Though there have
      been many structure and fusion studies of cellular and viral fusion proteins in
      the last years, their functional mechanism remains elusive. In particular, the
      structural modes of operation of the transmembrane domains and viral fusion
      peptides of fusion proteins during membrane fusion have not been elucidated,
      although work on de novo designed fusogenic peptides suggested that
      conformational flexibility was necessary. In addition, the use of different and
      incompatible measurement criteria has made a comparative overview difficult.
      Here, we report a systematic structural analysis of viral fusion peptides from
      different fusion protein classes and transmembrane domains of viral and cellular
      fusion proteins by using circular dichroism spectroscopy. The data that were
      obtained demonstrate that class I viral fusion peptides show a structural
      flexibility between helix and irregular secondary structures, whereas fusion
      peptides of class II viral fusion proteins are characterized by a stable random
      coil and turn structure. Thus, conformational flexibility does not seem to be a
      universal criterion for the fusion activity of a fusion peptide. On the contrary,
      the transmembrane domains of fusion proteins are distinguished by a structural
      flexibility between helix and sheet structure that is similar to de novo designed
      unnatural peptides with high fusion activities (M. W. Hofmann et al. PNAS 2004,
      101, 14 776-14 781). Thus, the conformational behavior of the fusogenic unnatural
      peptides most closely resembles that of fusion protein transmembrane domains, and
      allows them to be used to gain a deeper understanding of the membrane fusion
      process.

PMID- 18330853
TI  - Characterization of a new glycosynthase cloned by using chemical complementation.

PMID- 18330854
TI  - A multimeric quinacrine conjugate as a potential inhibitor of Alzheimer's beta
      amyloid fibril formation.
AB  - Amyloid formation and accumulation of the amyloid beta-peptide (Abeta) in the
      brain is associated with Alzheimer's disease (AD) pathogenesis. Therefore, among
      the therapeutic approaches in development to fight the disease, the direct
      inhibition of the Abeta self-assembly process is currently widely investigated
      and is one of the most promising approaches. In this study we investigated the
      potential of a multimeric display of quinacrine derivatives, as compared to the
      monomer quinacrine, as a design principal for a novel class of inhibitors against
      Abeta fibril formation. The presented multimeric conjugate exhibits a cluster of
      four quinacrine derivatives on a rigid cyclopeptidic scaffold. Herein is reported
      the synthesis of the conjugate, together with the in vitro inhibitory evaluation
      of Abeta(1-40) fibrils using the thioflavin T fluorescence assay, and imaging
      with atomic force microscopy. Our data show that the multimeric compound inhibits
      Abeta(1-40) fibril formation with an IC(50) value of 20+/-10 microM, which
      contrasts with the nonactive monomeric analogue. This work suggests that
      assembling multiple copies of acridine moieties to a central scaffold, for
      multiple interactions, is a promising strategy for the engineering of inhibitors
      against Abeta fibril formation.

PMID- 18330855
TI  - Complexation and fluorescence of tricyclic basic dyes encapsulated in
      cucurbiturils.
AB  - Tricyclic basic dyes (proflavine, acridine orange, pyronine, pyronine Y, oxonine,
      thionine and methylene blue) often form one-to-one or two-to-one complexes with
      CB[7] and CB[8], respectively. In the case of pyronine Y, the complexes with
      CB[7] and CB[8] have a one-to-one and three-to-one stoichiometry, respectively.
      The binding constants for CB[7] complexes range from 3.07x10(6) to 1.70x10(7) m(
      1). In the case of CB[8], the association constant varies between 3.24x10(13) and
      2.50x10(16) m(-2). Overall, these binding constants are four orders of magnitude
      higher than those reported for the same dyes in beta and gamma-cyclodextrins.
      Formation of the host-guest complexes leads to an increase in the fluorescence
      quantum yields in the case of CB[7], while the dimeric or trimeric dye
      encapsulated in CB[8] are remarkably less fluorescent than the same dye in
      diluted solutions.

PMID- 18330856
TI  - Resonance Raman cross-sections and vibronic analysis of rhodamine 6G from
      broadband stimulated Raman spectroscopy.

PMID- 18330857
TI  - Ketene thermochemistry.

PMID- 18330858
TI  - Clinical consequences of an increasing trend of preferential use of cultured
      villi for molecular diagnosis by CVS.
AB  - OBJECTIVE: To compare the use of uncultured versus cultured villus cells for DNA
      based prenatal diagnosis. METHODS: A retrospective review of molecular testing of
      chorionic villus sampling (CVS) cases from 1988-2007. Method of analysis,
      gestational age (GA) at CVS and at diagnosis, time from procedure to results,
      results of maternal contamination studies, and the laboratory employed were
      abstracted from patient charts. Trends in laboratory practices over time were
      analyzed. RESULTS: Time from CVS to diagnosis was longer when cultured cells were
      used. Average GA at diagnosis was 14-6/7 weeks with cultured cells vs 13-0/7
      weeks with uncultured villi (p < 0.001). Recently, laboratories are more
      frequently requiring cultured cells, resulting in significantly greater delays in
      time to diagnosis and GA at results. CONCLUSIONS: 'Direct' DNA extraction saves 2
      weeks from CVS to results. More women are afforded the option of an earlier,
      safer pregnancy termination if uncultured villi are used for molecular diagnosis.
      Implementation of standardized DNA extraction protocols and sample-size
      requirements can optimize the use of uncultured villi for molecular prenatal
      diagnosis. Increased awareness of the importance of rapid results and the
      advantages of 'direct' DNA extraction from uncultured villi can lead to
      improvements that are of clinical significance for patients undergoing early
      prenatal diagnosis.

PMID- 18330859
TI  - Postnatal management and outcome of prenatally diagnosed lung lesions.
AB  - Advancements in fetal diagnostic imaging have increased prenatal diagnosis of
      many fetal anomalies. The purpose of this chapter is to review the etiology and
      natural history of prenatally diagnosed cystic lung lesions, including congenital
      cystic adenomatoid malformations (CCAM), pulmonary sequestrations (PSs), hybrid
      lesions, and bronchogenic cysts, and then discuss current concepts in the
      management and outcome of these lesions.

PMID- 18330860
TI  - Twin-twin transfusion syndrome: mathematical modelling.
AB  - Twin-twin transfusion syndrome (TTTS) represents a pregnancy complication with a
      high risk for perinatal mortality and postnatal morbidity. Mathematical models
      have been utilized to examine the mechanisms of disease and potential treatment
      modalities. We developed four consecutive models based on pathophysiology
      mechanisms. Conceptually, these models remained simple, but with increased
      complexity in details. We present our models tutorially with the necessary
      equations expressed in words. The aetiology of TTTS was related to AV anastomoses
      from donor to recipient and their growth commensurate with placental growth. We
      assessed that natural growth of placenta and foetuses causes the diameter and
      length of the AV, as well as the AV's pressure gradient, to increase proportional
      to gestational age. The AV transfusion then increases faster than natural foetal
      growth. A progressively increasing discordance subsequently develops, not
      compensated for by foetal growth. A simulation is performed to show how this
      discordance in blood volumetric development causes successive discordances in
      other functions, particularly renal, circulatory, and cardio-vascular, resulting
      in disease progression to the various stages of TTTS. In conclusion, mathematical
      modelling of TTTS has provided an understanding of the sequence of events that
      leads to the various presentations of TTTS stages as well as the efficacy of
      therapies.

PMID- 18330861
TI  - Inhibin-A concentrations between 14 and 22 weeks of gestation.

PMID- 18330865
TI  - Templated synthesis of highly stable, electroactive, and dynamic metal-DNA
      branched junctions.

PMID- 18330867
TI  - Prenatal diagnosis of megalencephalic leukodystrophy.

PMID- 18330868
TI  - Diffusion of surgical innovation among patients with kidney cancer.
AB  - BACKGROUND: Despite their potential benefits to patients with kidney cancer, the
      adoption of partial nephrectomy and laparoscopy has been gradual and asymmetric.
      To clarify whether this trend reflects differences in kidney cancer patients or
      differences in surgeon practice styles, the authors compared the magnitude of
      surgeon-attributable variance in the use of partial nephrectomy and laparoscopic
      radical nephrectomy with that attributable to patient and tumor characteristics.
      METHODS: By using linked Surveillance, Epidemiology, and End Results-Medicare
      data, the authors identified a cohort of 5483 Medicare beneficiaries who
      underwent surgery for kidney cancer between 1997 and 2002. Two primary outcomes
      were defined: 1) the use of partial nephrectomy and (2) the use of laparoscopy
      among patients undergoing radical nephrectomy. By using multilevel models,
      surgeon- and patient-level contributions to observed variations in the use of
      partial nephrectomy and laparoscopic radical nephrectomy were estimated. RESULTS:
      Of the 5483 cases identified, 611 (11.1%) underwent partial nephrectomy (43
      performed laparoscopically), and 4872 (88.9%) underwent radical nephrectomy (515
      performed laparoscopically). After adjusting for patient demographics,
      comorbidity, tumor size, and surgeon volume, the surgeon-attributable variance
      was 18.1% for partial nephrectomy and 37.4% for laparoscopy. For both outcomes,
      the percentage of total variance attributable to surgeon factors was consistently
      higher than that attributable to patient characteristics. CONCLUSIONS: For many
      patients with kidney cancer, the surgery provided depends more on their surgeon's
      practice style than on the characteristics of the patient and his or her disease.
      Consequently, dismantling barriers to surgeon adoption of partial nephrectomy and
      laparoscopy is an important step toward improving the quality of care for
      patients with early-stage kidney cancer.

PMID- 18330869
TI  - Learning curve for Doppler assessment of ductus venosus flow at 11 + 0 to 13 + 6
      weeks' gestation.
AB  - OBJECTIVE: To determine the number of scans necessary for training sonographers
      to examine accurately the ductus venosus at 11 + 0 to 13 + 6 weeks' gestation.
      METHODS: Ten sonographers with prior extensive experience in the measurement of
      nuchal translucency thickness were given practical training in the accurate
      assessment of the ductus venosus. They were then asked to examine the ductus
      venosus during the routine 11 + 0 to 13 + 6 weeks' scan. Each scan was assessed
      by an experienced sonographer and classified as being successful or unsuccessful
      (failure to obtain a waveform, poor quality image with contamination or wrong
      classification of the A-wave). Each sonographer performed a total of 300
      examinations, the data were analyzed in 15 groups of 20 examinations and in each
      group the percentage of unsuccessful examinations was calculated. RESULTS: In the
      total 3000 cases examined by the 10 sonographers there were 2849 (95.0%)
      successful examinations and 151 unsuccessful, including 104 failures to obtain a
      waveform, 30 cases where the quality of the image was considered to be inadequate
      and 17 cases in which the classification of the A-wave was wrong. The overall
      frequency of unsuccessful examinations decreased significantly with the number of
      scans carried out (r = 0.982, P < 0.0001). The sonographers required an average
      of 80 examinations before they could successfully examine the ductus in at least
      19 of a group of 20 scans. Although one of the 10 trainees achieved this standard
      within the first block of 20 scans some of the sonographers required training in
      100 cases. CONCLUSION: Competence in Doppler assessment of the ductus venosus is
      achieved only after extensive supervised training.

PMID- 18330870
TI  - Functional architecture of verbal and tonal working memory: an FMRI study.
AB  - This study investigates the functional architecture of working memory (WM) for
      verbal and tonal information during rehearsal and articulatory suppression.
      Participants were presented with strings of four sung syllables with the task to
      remember either the pitches (tonal information) or the syllables (verbal
      information). Rehearsal of verbal, as well as of tonal information activated a
      network comprising ventrolateral premotor cortex (encroaching Broca's area),
      dorsal premotor cortex, the planum temporale, inferior parietal lobe, the
      anterior insula, subcortical structures (basal ganglia and thalamus), as well as
      the cerebellum. The topography of activations was virtually identical for the
      rehearsal of syllables and pitches, showing a remarkable overlap of the WM
      components for the rehearsal of verbal and tonal information. When the WM task
      was performed under articulatory suppression, activations in those areas
      decreased, while additional activations arose in anterior prefrontal areas. These
      prefrontal areas might contain additional storage components of verbal and tonal
      WM that are activated when auditory information cannot be rehearsed. As in the
      rehearsal conditions, the topography of activations under articulatory
      suppression was nearly identical for the verbal as compared to the tonal task.
      Results indicate that both the rehearsal of verbal and tonal information, as well
      as storage of verbal and tonal information relies on strongly overlapping
      neuronal networks. These networks appear to partly consist of sensorimotor
      related circuits which provide resources for the representation and maintenance
      of information, and which are remarkably similar for the production of speech and
      song.

PMID- 18330871
TI  - Patterns of cerebral activation during olfactory and trigeminal stimulations.
AB  - It is well known that most odorants stimulate both the olfactory system and the
      trigeminal system. However, the overlap between the brain processes involved in
      each of these sensorial perceptions is still poorly documented. This study aims
      to compare fMRI brain activations while smelling two odorants of a similar
      perceived intensity and pleasantness: phenyl ethyl alcohol (a pure olfactory
      stimulus) and iso-amyl-acetate (a bimodal olfactory-trigeminal stimulus) in a
      homogeneous sample of 15 healthy, right-handed female subjects. The analysis
      deals with the contrasts of brain activation patterns between these two odorant
      conditions. The results showed a significant recruitment of the right insular
      cortex, and bilaterally in the cingulate in response to the trigeminal component.
      These findings are discussed in relation to the characteristics of these odorants
      compared with those tested in previous studies.

PMID- 18330873
TI  - Three-dimensional ultrasound improves the interobserver reliability of antral
      follicle counts and facilitates increased clinical work flow.
AB  - OBJECTIVES: To compare the interobserver reliability of antral follicle counts
      made using real-time two-dimensional (2D) ultrasound with offline counts made
      from stored three-dimensional (3D) data and to assess the time required for such
      counts. METHODS: Two observers conducted transvaginal ultrasound examinations in
      45 subfertile women in the early follicular phase of the menstrual cycle. Antral
      follicles were counted using real-time 2D ultrasound and the time taken was
      recorded. A 3D volume was then acquired from each ovary and stored for subsequent
      offline analysis using the multiplanar view. The time taken for each step was
      recorded and the total time was calculated. Intraclass correlation coefficients
      (ICC) and limits of agreement were used to assess reliability. RESULTS: There was
      no difference in the mean antral follicle counts using real-time 2D (16.51 +/-
      11.51) and 3D (16.33 +/- 12.13) ultrasound. According to ICCs, there was a
      significantly higher interobserver reliability for counts made using 3D (mean,
      0.992; 95% CI, 0.986-0.996) compared with real-time 2D (mean, 0.961; 95% CI,
      0.940-0.977) (P < 0.01) ultrasound. 3D ultrasound was also associated with
      narrower limits of agreement (-2.7 to + 3.1) than was 2D ultrasound (-6.9 to +
      6.4). Whilst the total time taken was significantly longer for the 3D technique
      (239.3 +/- 71.4 s vs. 103.1 +/- 28.6 s, P < 0.001), the time required for the
      actual ultrasound examination was significantly less (46.4 +/- 7.4 s vs. 103.1 +/
      28.6 s, P < 0.001). CONCLUSIONS: 3D ultrasound significantly improves the
      interobserver reliability of antral follicle counts. While this is at the expense
      of time overall, the duration of the actual ultrasound examination and patient
      exposure is significantly reduced using 3D compared with real-time 2D ultrasound.

PMID- 18330872
TI  - Developmental differences of neurocognitive networks for phonological and
      semantic processing in Chinese word reading.
AB  - Developmental differences in the neurocognitive networks for phonological and
      semantic processing in Chinese word reading were examined in 13 adults and 13
      children using functional magnetic resonance imaging (fMRI). Rhyming and semantic
      association judgments were made to two-character words that were presented
      sequentially in the visual modality. These lexical tasks were compared with a
      nonlinguistic control task involving judgment of line patterns. The first main
      finding was that adults showed greater activation than children in right middle
      occipital gyrus on both the meaning and rhyming task, suggesting adults more
      effectively engage right hemisphere brain regions involved in the visual-spatial
      analysis of Chinese characters. The second main finding was that adults showed
      greater activation than children in left inferior parietal lobule for the rhyming
      as compared with the meaning task, suggesting greater specialization of
      phonological processing in adults. The third main finding was that children who
      had better performance in the rhyming task on characters with conflicting
      orthographic and phonological information relative to characters with
      nonconflicting information showed greater activation in left middle frontal
      gyrus, suggesting greater engagement of brain regions involved in the integration
      of orthography and phonology.

PMID- 18330874
TI  - Photoinduced release of guest molecules by supramolecular transformation of self
      assembled aggregates derived from dendrons.

PMID- 18330875
TI  - S4(2-) rings, disulfides, and sulfides in transition-metal complexes: the subtle
      interplay of oxidation and structure.

PMID- 18330876
TI  - Sequence-based design of alpha/beta-peptide foldamers that mimic BH3 domains.

PMID- 18330877
TI  - Evolution of chemical bonding during HCN <==> HNC isomerization as revealed
      through nuclear quadrupole hyperfine structure.

PMID- 18330878
TI  - Porous, covalent triazine-based frameworks prepared by ionothermal synthesis.

PMID- 18330879
TI  - A nitrido-centered uranium azido cluster obtained from a uranium azide.

PMID- 18330880
TI  - The groves-spiro dioxomanganese(v) story.

PMID- 18330881
TI  - Distannylations and silastannylations of in situ generated allenes.

PMID- 18330882
TI  - Helical (5Z, 11E)-dibenzo[a,e]cyclooctatetrene: a spring-loaded monomer.

PMID- 18330883
TI  - Expanding the synthetic potential of asymmetric deprotonation: arylation of
      carbanions.

PMID- 18330884
TI  - Transparent carbon films as electrodes in organic solar cells.

PMID- 18330885
TI  - Pyrin, product of the MEFV locus, interacts with the proapoptotic protein, Siva.
AB  - Mutations in pyrin cause the autoinflammatory disorder familial Mediterranean
      fever (FMF), a syndrome characterized by sporadic and unpredictable attacks of
      fever and localized severe pain. Currently, it is not clear how attacks are
      triggered, nor why they spontaneously resolve after 2 or 3 days. In fact, the
      cellular function of the pyrin protein and the molecular underpinnings of its
      malfunction in FMF have so far eluded clear definition. The identification of
      pyrin-interacting proteins has the potential to increase our understanding of the
      cellular networks in which pyrin functions. Previous reports have established
      that pyrin interacts with the apoptotic protein ASC, the cytoskeletal adaptor
      protein PSTPIP1, the inflammatory caspase, Caspase-1 and certain forms of the
      cytosolic anchoring protein 14-3-3. Here, we report that pyrin also interacts
      with Siva, a pro-apoptotic protein first identified for its interaction with the
      cytosolic tail of CD27, a TNF family receptor. The interaction between pyrin and
      Siva involves the C-terminal B30.2/rfp/SRPY domain of pyrin and exon 1 of Siva.
      We show that Siva and pyrin are indeed co-expressed in human neutrophils,
      monocytes, and synovial cells. Furthermore, using a novel protein/protein
      interaction assay, we demonstrate that pyrin can recruit Siva to ASC specks,
      establishing a potential platform for intersection of ASC and Siva function.
      Finally, we show that pyrin modulates the apoptotic response to oxidative stress
      mediated by Siva. Thus, the Siva-pyrin interaction may be a potential target for
      future therapeutic strategies.

PMID- 18330886
TI  - Viral vectors for production of recombinant proteins in plants.
AB  - Global demand for recombinant proteins has steadily accelerated for the last 20
      years. These recombinant proteins have a wide range of important applications,
      including vaccines and therapeutics for human and animal health, industrial
      enzymes, new materials and components of novel nano-particles for various
      applications. The majority of recombinant proteins are produced by traditional
      biological "factories," that is, predominantly mammalian and microbial cell
      cultures along with yeast and insect cells. However, these traditional
      technologies cannot satisfy the increasing market demand due to prohibitive
      capital investment requirements. During the last two decades, plants have been
      under intensive investigation to provide an alternative system for cost
      effective, highly scalable, and safe production of recombinant proteins. Although
      the genetic engineering of plant viral vectors for heterologous gene expression
      can be dated back to the early 1980s, recent understanding of plant virology and
      technical progress in molecular biology have allowed for significant improvements
      and fine tuning of these vectors. These breakthroughs enable the flourishing of a
      variety of new viral-based expression systems and their wide application by
      academic and industry groups. In this review, we describe the principal plant
      viral-based production strategies and the latest plant viral expression systems,
      with a particular focus on the variety of proteins produced and their
      applications. We will summarize the recent progress in the downstream processing
      of plant materials for efficient extraction and purification of recombinant
      proteins.

PMID- 18330887
TI  - The geodiamolide H, derived from Brazilian sponge Geodia corticostylifera,
      regulates actin cytoskeleton, migration and invasion of breast cancer cells
      cultured in three-dimensional environment.
AB  - We are investigating effects of the depsipeptide geodiamolide H, isolated from
      the Brazilian sponge Geodia corticostylifera, on cancer cell lines grown in 3D
      environment. As shown previously geodiamolide H disrupts actin cytoskeleton in
      both sea urchin eggs and breast cancer cell monolayers. We used a normal mammary
      epithelial cell line MCF 10A that in 3D assay results formation of polarized
      spheroids. We also used cell lines derived from breast tumors with different
      degrees of differentiation: MCF7 positive for estrogen receptor and the Hs578T,
      negative for hormone receptors. Cells were placed on top of Matrigel. Spheroids
      obtained from these cultures were treated with geodiamolide H. Control and
      treated samples were analyzed by light and confocal microscopy. Geodiamolide H
      dramatically affected the poorly differentiated and aggressive Hs578T cell line.
      The peptide reverted Hs578T malignant phenotype to polarized spheroid-like
      structures. MCF7 cells treated by geodiamolide H exhibited polarization compared
      to controls. Geodiamolide H induced striking phenotypic modifications in Hs578T
      cell line and disruption of actin cytoskeleton. We investigated effects of
      geodiamolide H on migration and invasion of Hs578T cells. Time-lapse microscopy
      showed that the peptide inhibited migration of these cells in a dose-dependent
      manner. Furthermore invasion assays revealed that geodiamolide H induced a 30%
      decrease on invasive behavior of Hs578T cells. Our results suggest that
      geodiamolide H inhibits migration and invasion of Hs578T cells probably through
      modifications in actin cytoskeleton. The fact that normal cell lines were not
      affected by treatment with geodiamolide H stimulates new studies towards
      therapeutic use for this peptide.

PMID- 18330888
TI  - Cell autonomous function of Nogo and reticulons: The emerging story at the
      endoplasmic reticulum.
AB  - The myelin-associated membrane protein reticulon-4 (RTN4)/Nogo has been
      extensively studied with regards to its neurite outgrowth inhibitory function,
      both in limiting plasticity in the healthy adult brain and regeneration during
      central nervous system injury. These activities are presumably associated with
      Nogo splice isoforms expressed on the cell surface and function largely in trans,
      exerting an influence as an intercellular membrane-bound ligand. Nogo, and other
      reticulon paralogues and orthologues, are however mainly localized to the
      endoplasmic reticulum (ER), and are likely to have cell autonomous functions that
      are not yet clear. Emerging evidence suggests that Nogo may have a role in
      modulating the morphology and functions of the ER. This role is apparently not
      essential for cell viability under normal growth conditions, but may be
      manifested under certain stress conditions.

PMID- 18330889
TI  - P53 mutations in colorectal cancer from northern Iran: Relationships with site of
      tumor origin, microsatellite instability and K-ras mutations.
AB  - CRC-associated P53 mutations have not been studied extensively in non-Western
      countries at relatively low CRC risk. We examined, for the first time, 196
      paraffin-embedded CRC cases from Northern Iran for mutations in P53 exons 5-8
      using PCR-direct sequencing. P53 status and mutation site/type were correlated
      with nuclear protein accumulation, clinicopathologic variables and data on K-ras
      mutations and high-level microsatellite instability (MSI-H). We detected 96 P53
      mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53
      mutations correlated directly with stage and inversely with MSI-H. Distal CRCs
      were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175
      (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213,
      emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048).
      Transitions at CpGs, the most common mutation type, were more frequent in non
      mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in
      proximal, P = 0.02), and correlated with K-ras transversions. Transitions at non
      CpGs, second most common P53 mutation, were more frequent in proximal tumors
      (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K-ras transitions and
      MSI-H. Overall frequency and types of mutations and correlations with P53
      accumulation, stage and MSI-H were as reported for non-Iranian patients. However
      P53 mutation site/type and correlations between P53 and K-ras mutation types
      differed between proximal and distal CRC. The codon 213 P53 mutation that
      recurred in proximal CRC was previously reported as frequent in esophageal cancer
      from Northern Iran.

PMID- 18330890
TI  - Laser coagulation of placental anastomoses with a 30 degrees fetoscope in severe
      mid-trimester twin-twin transfusion syndrome with anterior placenta.
AB  - OBJECTIVE: To assess outcome after fetoscopic laser coagulation (FLC) of
      placental vascular anastomoses with the 30 degrees fetoscope in mid-trimester
      severe twin-to-twin transfusion syndrome (TTTS) with completely anterior placenta
      compared with the regular 0 degrees fetoscope in TTTS with other placental
      locations. METHODS: This was a prospective study of 176 consecutive monochorionic
      twin pregnancies undergoing FLC for severe TTTS. Of these, 51 patients required
      use of the 30 degrees fetoscope (study group) and 125 placental locations
      permitted use of the 0 degrees fetoscope (controls). RESULTS: The two groups had
      very similar outcomes. The median gestational age at FLC in the study group vs.
      control group was 21.0 (range, 17.4-24.6) weeks vs. 20.6 (range, 15.9-24.6)
      weeks. Both fetuses survived in 58.8% (30/51) of study patients vs. 66.4%
      (83/125) of controls. At least one fetus survived in 84.3% (43/51) of study
      patients and 88.8% (111/125) of controls (P = 0.45). Study patients delivered at
      a median of 34.1 (range, 25.0-38.4) weeks and controls at 34.0 (range, 25.0-40.3)
      weeks' gestation. CONCLUSIONS: Use of a 30 degrees fetoscope for FLC in cases of
      technically challenging extensive anterior placentation is associated with an
      outcome that is very similar to that achieved when a 0 degrees fetoscope is used
      in cases of more favorable placental location.

PMID- 18330891
TI  - Integrin alpha5-induced EGFR activation by prothrombin triggers hepatocyte
      apoptosis via the JNK signaling pathway.
AB  - We have previously shown that prothrombin, a blood coagulation factor, can cause
      an inhibition of DNA synthesis in normal rat hepatocytes. To explore the
      mechanisms of this prothrombin action, we examined its effects on the activation
      of fibronectin receptor integrin alpha5, since fibronectin was found to be
      degraded by prothrombin actions in primary hepatocyte cultures. We found that
      prothrombin treatment of rat hepatocytes without addition of any growth factor
      induced tyrosine phosphorylation of integrin alpha5 and interaction of integrin
      alpha5 with epidermal growth factor receptor (EGFR), leading to EGFR tyrosine
      phosphorylation at tyrosine residues Tyr-845 and Tyr-1173. EGFR tyrosine
      phosphorylation triggered phosphorylation of its down-stream target Shc and the
      activation of the c-Jun N-terminal kinase (JNK) pathway. Prothrombin also induced
      hepatocyte apoptosis, a change in cell shape and activation of caspase 3 pathway.
      The JNK pathway is most likely involved in prothrombin-induced hepatocyte
      apoptosis, because pre-treatment of hepatocytes with JNK kinase inhibitor II
      (SP600125) antagonized these prothrombin actions. The data suggest that integrin
      related EGFR activation by prothrombin can induce cell growth inhibition and
      apoptosis via an EGFR-JNK signaling pathway.

PMID- 18330892
TI  - Topical administration of a multi-targeted kinase inhibitor suppresses choroidal
      neovascularization and retinal edema.
AB  - Age-related macular degeneration, diabetic retinopathy, and retinal vein
      occlusions are complicated by neovascularization and macular edema. Multi
      targeted kinase inhibitors that inhibit select growth factor receptor tyrosine
      kinases and/or components of their down-stream signaling cascades (such as Src
      kinases) are rationale treatment strategies for these disease processes. We
      describe the discovery and characterization of two such agents. TG100572, which
      inhibits Src kinases and selected receptor tyrosine kinases, induced apoptosis of
      proliferating endothelial cells in vitro. Systemic delivery of TG100572 in a
      murine model of laser-induced choroidal neovascularization (CNV) caused
      significant suppression of CNV, but with an associated weight loss suggestive of
      systemic toxicity. To minimize systemic exposure, topical delivery of TG100572 to
      the cornea was explored, and while substantial levels of TG100572 were achieved
      in the retina and choroid, superior exposure levels were achieved using TG100801,
      an inactive prodrug that generates TG100572 by de-esterification. Neither
      TG100801 nor TG100572 were detectable in plasma following topical delivery of
      TG100801, and adverse safety signals (such as weight loss) were not observed even
      with prolonged dosing schedules. Topical TG100801 significantly suppressed laser
      induced CNV in mice, and reduced fluorescein leakage from the vasculature and
      retinal thickening measured by optical coherence tomography in a rat model of
      retinal vein occlusion. These data suggest that TG100801 may provide a new
      topically applied treatment approach for ocular neovascularization and retinal
      edema.

PMID- 18330893
TI  - Effect of dihydrotestosterone on hydrogen peroxide-induced apoptosis of mouse
      embryonic stem cells.
AB  - Steroid hormones have been reported to activate various signal transducers that
      trigger a variety of cellular responses. Among these hormones, testosterone has
      been identified as an antioxidant that protects against cellular damage.
      Therefore, using mouse embryonic stem (ES) cells as a model system, this study
      evaluated the effects of dihydrotestosterone (DHT), a biologically active
      testosterone metabolite, on H2O2-induced apoptosis. H2O2 increased the release of
      lactate dehydrogenase (LDH) and DNA fragmentation but reduced the cell viability
      in a time-dependent manner (> or =8 h). Moreover, H2O2 decreased the level of DNA
      synthesis and the levels of the cell cycle regulatory proteins [cyclin D1, cyclin
      E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H2O2 were
      inhibited by a pretreatment with DHT. However, a treatment with flutamide
      (androgen receptor inhibitor, 10(-3) M) abolished the protective effects of DHT.
      This result was supported by the presence of the androgen receptor in mouse ES
      cells. The activity of the antioxidant enzyme, catalase, was increased by the DHT
      treatment but not by a co-treatment with DHT and flutamide. Using CM-H(2)DCFDA
      (DCF-DA) for the detection of intracellular H2O2, DHT decreased the intracellular
      H2O2 levels but flutamide blocked this effect. H2O2 also increased the level of
      p38 MAPK, JNK/SAPK, and NF-kappaB phosphorylation, which were inhibited by the
      DHT pretreatment. Catalase inhibited the effect of H2O2 on MAPKs and NF-kappaB.
      However, the flutamide treatment abolished the inhibitory effects of DHT on the
      H2O2-induced increase in the levels of p38 MAPK, JNK/SAPK, and NF-kappaB
      phosphorylation. DHT inhibited the H2O2-induced increase in caspase-3 expression
      and decreased the level of Bcl-2 and the cellular inhibitor of apoptosis protein
      (cIAP)-2. These effects were abolished by the flutamide treatment. In conclusion,
      DHT prevents the H2O2-induced apoptotic cell death of mouse ES cells through the
      activation of catalase and the downregulation of p38 MAPK, JNK/SAPK, and NF
      kappaB via the androgen receptor.

PMID- 18330894
TI  - Occupational health and safety experience of day laborers in Seattle, WA.
AB  - BACKGROUND: Day Labor is a growing part of the informal economy in the US, and in
      Seattle, and may entail a high risk of injury and illness at work. METHODS: We
      surveyed 180-day laborers, at two worker centers and an unregulated "Street"
      location concerning their job-specific exposures and injury experience. RESULTS:
      Exposures to both health and safety hazards were common at all three sites. After
      controlling for type of work, immigrant workers were 1.5-2 times more likely than
      non-immigrant day laborers to report exposure to hazardous conditions. Among the
      180 participants 34 reported injuries were classified as "recordable." We
      estimated an injury rate of 31 recordable injuries per 100 full time employees.
      The three hiring locations had differing job experiences and exposures. Those
      hired through worker centers had a lower risk of exposures, while the Street
      workers were more likely to refuse hazardous work. CONCLUSIONS: Day laborers are
      exposed to numerous hazards at work, resulting in high injury rates. Multiple
      approaches including community based organizations which may provide some
      employment stability and social support for protection at work are needed to
      reduce occupational injury and illness risk among these vulnerable populations.

PMID- 18330895
TI  - Cloning, expression, and localization of a molt-related beta-N
      acetylglucosaminidase in the spruce budworm, Choristoneura fumiferana.
AB  - A beta-N-acetylglucosaminidase cDNA (CfGlcNAcase) was cloned from the spruce
      budworm, Choristoneura fumiferana. Western blotting analysis of developmental
      CfGlcNAcase expression revealed high levels of expression of the gene on the last
      day of the 5th instar larvae and the first day in the 6th instar larvae, followed
      by a decrease to background levels during the intermolt of the 6th instar.
      CfGlcNAcase was detected again from the last day of the 6th instar to day 2 of
      pupal stage. CfGlcNAcase expression was induced by tebufenozide at 24 h post
      treatment and remained at high levels until 72 h. Immunohistochemical
      localization analysis of CfGlcNAcase indicated that CfGlcNAcase was present in
      the molting fluid, epidermis, trachea, and hemolymph in prepupae during the
      transformation from larva to pupa. CfGlcNAcase cDNA was expressed into a
      recombinant protein in bacterial and baculovirus systems and the protein
      expressed in the baculovirus system had a higher chitinolytic activity than in
      the bacterial system and appeared to be secreted.

PMID- 18330896
TI  - An experimental study of nettle feeding in captive gorillas.
AB  - Mountain gorillas (Gorilla beringei beringei) in Karisoke, Rwanda, feed on the
      stinging nettle Laportea alatipes by means of elaborate processing skills. Byrne
      [e.g. Philosophical Transactions of the Royal Society of London, Series B,
      Biological Sciences 358:529-536, 2003] has claimed that individuals acquire these
      skills by means of the so-called program-level imitation, in which the overall
      sequence of problem-solving steps (not the precise actions) is reproduced. In
      this study we present western lowland gorillas (Gorilla gorilla gorilla) with
      highly similar nettles. Twelve gorillas in three different groups (including also
      one nettle-naive gorilla) used the same program-level technique as wild mountain
      gorillas (with differences mainly on the action level). Chimpanzees, orangutans,
      and bonobos did not show these program-level patterns, nor did the gorillas when
      presented with a plant similar in structural design but lacking stinging
      defenses. We conclude that although certain aspects (i.e. single actions) of this
      complex skill may be owing to social learning, at the program level gorilla
      nettle feeding derives mostly from genetic predispositions and individual
      learning of plant affordances.

PMID- 18330897
TI  - Overexpression of HmgD causes the failure of pupariation in Drosophila by
      affecting ecdysone receptor pathway.
AB  - HmgD encodes Drosophila homologue of high mobility group proteins (HMGD), which
      are thought to have an architectural function in chromatin organization. However,
      current opinions about the function of HMGD in Drosophila development are
      controversial. Our previous studies have shown that ubiquitous overexpression of
      HmgD caused the formation of melanotic tumors in the Drosophila larvae by
      prematurely activating the Ras-MAPK pathway. Here we report that under maternal
      control, the viability of flies links with overexpression of HmgD, while under
      ubiquitous control, ActGal4, overexpressing HmgD animals, which display prolonged
      larval stages around day 13, developmentally stagnate in the larva-white pupa
      transition. Ecdysone feeding did not rescue overexpressing HmgD animals. RT-PCR
      analyses show that overexpression of HmgD does not affect the temporal expression
      pattern of ecdysone receptor gene EcR, whereas transcriptional patterns of some
      key regulatory genes, such as E74A, E74B, E75A, E75B, betaFTZ-F1, are changed
      greatly. These results suggest that ubiquitous overexpression of HmgD results in
      the failure of pupariation neither by affecting the process of ecdysone synthesis
      and release nor by abnormal EcR transcription, but by causing expression of EcR
      regulatory nuclear receptors out of schedule. The results led us to postulate
      that overexpression of HMGD likely changes the signaling cascade of Drosophila
      metamorphosis by an interaction between HMGD and DNA strands, and subsequently by
      an error of DNA binding abilities and transcriptional activities of some nuclear
      receptor genes. Arch. Insect Biochem. Physiol. 2008.

PMID- 18330898
TI  - Maternal and infantile dietary salt exposure may cause hypertension later in
      life.

PMID- 18330899
TI  - MYH9-siRNA and MYH9 mutant alleles: expression in cultured cell lines and their
      effects upon cell structure and function.
AB  - MYH9 encodes a class II nonmuscle myosin heavy chain-A (NMHC-IIA), a widely
      expressed 1960 amino acid polypeptide, with translated molecular weight of 220
      kDa. From studies of type II myosin in invertebrates and analogy with the
      skeletal and smooth muscle myosin II, NMHC-IIA is considered to be involved in
      diverse cellular functions, including cell shape, motility and division. The
      current study assessed the consequences of two separate, naturally occurring MYH9
      dominant mutant alleles, MYH9(R702C) and MYH9(R705H) linked to syndromic and
      nonsyndromic hearing loss, respectively, upon diverse NMHC-IIA related functions
      in two separate cultured cell lines. MYH9-siRNA-induced inhibition of NMHC-IIA in
      HeLa cells or HEK293 cells resulted in alterations in their shape, actin
      cytoskeleton and adhesion properties. However, HeLa or HEK293 cells transfected
      with naturally occurring MYH9 mutant alleles, MYH9(R702C) or MYH9(R705H), as well
      as in vitro generated deletion derivatives, MYH9(DeltaN592) or MYH9(DeltaC570),
      were unaffected. The effects of MYH9-siRNA-induced suppression underline the
      critical role of NMHC-IIA in maintenance of cell shape and adhesion. However, the
      results also indicate that the NMHC-IIA mutants, R702C and R705H do not
      inactivate or suppress the endogenous wild type NMHC-IIA within the HeLa or
      HEK293 cell assay system.

PMID- 18330900
TI  - Treponema denticola Msp-deduced peptide conjugate, P34BSA, promotes RhoA
      dependent actin stress fiber formation independent of its internalization by
      fibroblasts.
AB  - P34(BSA), a BSA conjugate of a synthetic 10-mer peptide deduced from Treponema
      denticola major outer sheath protein (Msp), stabilizes actin filaments in
      fibroblasts and retards cell motility. We reported previously that it is
      internalized by cells, binds and bundles actin filaments in vitro, and activates
      RhoA; yet, its site and mechanism of action were not defined. We have assessed
      P34(BSA)'s modes of interaction with and signaling to fibroblasts. At 4 degrees
      C, P34(BSA) was not internalized, but it bound to the plasma membrane and
      promoted actin stress fiber formation at approximately 80% capacity compared with
      37 degrees C controls, casting doubt that cellular uptake is a critical step for
      its cytoskeleton-stabilizing property. In Rho G-LISA and co-immunoprecipitation
      assays, P34(BSA) was found to activate RhoA, even at 4 degrees C, to promote its
      interaction with guanosine nucleotide exchange factor p114RhoGEF. It also caused
      phosphorylation of cofilin. Upon RhoA inhibition, either by C3 transferase RhoA
      inhibitor or by transfection with a dominant negative RhoA construct, P34(BSA)
      did not achieve the stress fiber formation seen with P34(BSA) alone. By
      inhibiting phosphatidylinositol-3 kinase (PI 3-K) with LY294002, the P34(BSA)
      effects were completely blocked. Depletion of cholesterol with methyl-beta
      cyclodextrin (MbetaCD) partially inhibited P34(BSA) signaling via the plasma
      membrane to the cytoskeleton. This suggests that multivalent P34(BSA) activation
      of lipid raft components requires active PI 3-K, and initiates the pathway
      through a RhoGEF and RhoA, which mediates stress fiber formation in fibroblasts.
      Hence, P34(BSA) may represent a novel tool to investigate RhoA-dependent
      processes, such as remodeling filamentous actin in eukaryotic cells.

PMID- 18330901
TI  - Myosin Va phosphorylated on Ser1650 is found in nuclear speckles and
      redistributes to nucleoli upon inhibition of transcription.
AB  - Nuclear actin and nuclear myosins have been implicated in the regulation of gene
      expression in vertebrate cells. Myosin V is a class of actin-based motor proteins
      involved in cytoplasmic vesicle transport and anchorage, spindle-pole alignment
      and mRNA translocation. In this study, myosin-Va, phosphorylated on a conserved
      serine in the tail domain (phospho-ser(1650) MVa), was localized to subnuclear
      compartments. A monoclonal antibody, 9E6, raised against a peptide corresponding
      to phosphoserine(1650) and flanking regions of the murine myosin Va sequence, was
      immunoreactive to myosin Va heavy chain in cellular and nuclear extracts of HeLa
      cells, PC12 cells and B16-F10 melanocytes. Immunofluorescence microscopy with
      this antibody revealed discrete irregular spots within the nucleoplasm that
      colocalized with SC35, a splicing factor that earmarks nuclear speckles. Phospho
      ser(1650) MVa was not detected in other nuclear compartments, such as condensed
      chromatin, Cajal bodies, gems and perinucleolar caps. Although nucleoli also were
      not labeled by 9E6 under normal conditions, inhibition of transcription in HeLa
      cells by actinomycin D caused the redistribution of phospho-ser(1650) MVa to
      nucleoli, as well as separating a fraction of phospho-ser(1650) MVa from SC35
      into near-neighboring particles. These observations indicate a novel role for
      myosin Va in nuclear compartmentalization and offer a new lead towards the
      understanding of actomyosin-based gene regulation.

PMID- 18330902
TI  - The hTAF II 68-TEC fusion protein functions as a strong transcriptional
      activator.
AB  - Human extraskeletal myxoid chondrosarcoma (EMC) is caused by a chromosomal
      translocation that involves TEC (translocated in extraskeletal myxoid
      chondrosarcoma), and either EWS (Ewing's sarcoma) or hTAF(II)68 (human TATA
      binding protein-associated factor II 68), which generates EWS-TEC or hTAF(II)68
      TEC fusion proteins, respectively. Although there has been a great deal of
      progress in characterizing EWS-TEC, there is relatively little known about the
      biological function of hTAF(II)68-TEC. We have examined the functional
      consequences of the fusion of the amino terminal domain (NTD) of hTAF(II)68 to
      TEC in EMC. The chimeric gene encodes a nuclear protein that binds DNA with the
      same sequence specificity as parental TEC. Nuclear localization of hTAF(II)68-TEC
      was dependent on the DNA binding domain, and we identified a cluster of basic
      amino acids in the DNA binding domain, KRRR, that specifically mediate the
      nuclear localization of hTAF(II)68-TEC. The transactivation activity of
      hTAF(II)68-TEC was higher than TEC towards a known target promoter that contained
      several TEC binding sites. Finally, deletion analysis of hTAF(II)68-TEC indicated
      that the hTAF(II)68 NTD, and the AF1 and AF2 domains of hTAF(II)68-TEC are
      necessary for full transactivation potential. These results suggest that the
      oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC
      chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein
      produces a gain of function chimeric product.

PMID- 18330903
TI  - Measuring and partitioning the high-order linkage disequilibrium by multiple
      order Markov chains.
AB  - A map of the background levels of disequilibrium between nearby markers can be
      useful for association mapping studies. In order to assess the background levels
      of linkage disequilibrium (LD), multilocus LD measures are more advantageous than
      pairwise LD measures because the combined analysis of pairwise LD measures is not
      adequate to detect simultaneous allele associations among multiple markers.
      Various multilocus LD measures based on haplotypes have been proposed. However,
      most of these measures provide a single index of association among multiple
      markers and does not reveal the complex patterns and different levels of LD
      structure. In this paper, we employ non-homogeneous, multiple order Markov Chain
      models as a statistical framework to measure and partition the LD among multiple
      markers into components due to different orders of marker associations. Using a
      sliding window of multiple markers on phased haplotype data, we compute
      corresponding likelihoods for different Markov Chain (MC) orders in each window.
      The log-likelihood difference between the lowest MC order model (MC0) and the
      highest MC order model in each window is used as a measure of the total LD or the
      overall deviation from the gametic equilibrium for the window. Then, we partition
      the total LD into lower order disequilibria and estimate the effects from two-,
      three-, and higher order disequilibria. The relationship between different orders
      of LD and the log-likelihood difference involving two different orders of MC
      models are explored. By applying our method to the phased haplotype data in the
      ENCODE regions of the HapMap project, we are able to identify high/low multilocus
      LD regions. Our results reveal that the most LD in the HapMap data is attributed
      to the LD between adjacent pairs of markers across the whole region. LD between
      adjacent pairs of markers appears to be more significant in high multilocus LD
      regions than in low multilocus LD regions. We also find that as the multilocus
      total LD increases, the effects of high-order LD tends to get weaker due to the
      lack of observed multilocus haplotypes. The overall estimates of first, second,
      third, and fourth order LD across the ENCODE regions are 64, 23, 9, and 3%.

PMID- 18330904
TI  - Using disease symptoms to improve detection of linkage under genetic
      heterogeneity.
AB  - A major reason for the slow progress in identifying susceptibility genes for
      complex diseases may be that the clinical diagnoses used as phenotypes are
      genetically heterogeneous. This has led researchers to collect various phenotypes
      related to the diagnosis, such as detailed symptoms, in the hope that these
      measurements define more homogeneous disease sub-types, influenced by a smaller
      number of genes that will thus be more easily detectable. Latent class analysis
      can be used to define disease sub-types from multivariate symptoms under the
      assumption that the subjects are independent, an assumption that does not hold
      between members of the same family. We have recently developed a latent class
      model allowing dependence between the latent disease class status of relatives
      within nuclear families. In this paper, we propose approaches to use the
      resulting latent class probabilities in linkage analysis. We present results from
      a simulation study showing that the latent class approach can provide a
      substantial gain in power to detect disease genes over the standard heterogeneity
      approach of Smith and identity-by-descent sharing methods applied to the disease
      diagnosis. Taking into account familial dependence in the latent class model
      generally provides greater power than assuming independence. In an analysis of
      autism symptoms in families from the Autism Genetics Research Exchange, linkage
      signals obtained with latent class-derived phenotypes were stronger than those
      obtained using the original autism spectrum disorder diagnosis.

PMID- 18330905
TI  - Searching for epistasis and linkage heterogeneity by correlations of pedigree
      specific linkage scores.
AB  - Recognizing that multiple genes are likely responsible for common complex traits,
      statistical methods are needed to rapidly screen for either interacting genes or
      locus heterogeneity in genetic linkage data. To achieve this, some investigators
      have proposed examining the correlation of pedigree linkage scores between pairs
      of chromosomal regions, because large positive correlations suggest interacting
      loci and large negative correlations suggest locus heterogeneity (Cox et al.
      [1999]; Maclean et al. [1993]). However, the statistical significance of these
      extreme correlations has been difficult to determine due to the autocorrelation
      of linkage scores along chromosomes. In this study, we provide novel solutions to
      this problem by using results from random field theory, combined with simulations
      to determine the null correlation for syntenic loci. Simulations illustrate that
      our new methods control the Type-I error rates, so that one can avoid the
      extremely conservative Bonferroni correction, as well as the extremely time
      consuming permutational method to compute P-values for non-syntenic loci.
      Application of these methods to prostate cancer linkage studies illustrates
      interpretation of results and provides insights into the impact of marker
      information content on the resulting statistical correlations, and ultimately the
      asymptotic P-values.

PMID- 18330906
TI  - Tracking changes in Z-band organization during myofibrillogenesis with FRET
      imaging.
AB  - There are a large number of proteins associated with Z-bands in myofibrils, but
      the precise arrangements of most of these proteins in Z-bands are largely
      unknown. Even less is known about how these arrangements change during
      myofibrillogenesis. We have begun to address this issue using Sensitized Emission
      Fluorescence Resonance Energy Transfer (SE-FRET) microscopy. Cultured skeletal
      muscle cells from quail embryos were transfected to express fusions of alpha
      actinin, FATZ, myotilin, or telethonin with cyan and yellow fluorescent proteins
      in various pair wise combinations. FATZ and myotilin were selected because
      previous biochemical studies have suggested that they bind to alpha-actinin, the
      major protein of the Z-band. Telethonin was selected for its reported ability to
      bind FATZ. Statistical analysis of data from FRET imaging studies yield results
      that are in agreement with published biochemical data suggesting that FATZ and
      myotilin bind to alpha-actinin near its C-terminus as well as to each other and
      that a region near the amino-terminus of FATZ is responsible for its interaction
      with telethonin. In addition, our analysis has revealed changes in the
      arrangement of alpha-actinin and FATZ that take place during the transition as
      the z-bodies of premyofibrils fuse to form the Z-bands of mature myofibrils.
      There was no evidence for a change in the arrangement of myotilin as z-bodies
      transformed into Z-bands. Myotilin is one Z-band protein that does not exhibit
      decreased dynamics as z-bodies fuse to form Z-bands. These FRET results from
      living cells support a stepwise model for the assembly of myofibrils.

PMID- 18330907
TI  - Anisotropic contraction in forisomes: simple models won't fit.
AB  - Forisomes are ATP-independent, Ca(2+)-driven contractile protein bodies acting as
      reversible valves in the phloem of plants of the legume family. Forisome
      contraction is anisotropic, as shrinkage in length is associated with radial
      expansion and vice versa. To test the hypothesis that changes in length and width
      are causally related, we monitored Ca(2+)- and pH-dependent deformations in the
      exceptionally large forisomes of Canavalia gladiata by high-speed photography,
      and computed time-courses of derived geometric parameters (including volume and
      surface area). Soybean forisomes, which in the resting state resemble those of
      Canavalia geometrically but have less than 2% of the volume, were also studied to
      identify size effects. Calcium induced sixfold volume increases in forisomes of
      both species; in soybean, responses were completed in 0.15 s, compared to about
      0.5 s required for a rapid response in Canavalia followed by slow swelling for
      several minutes. This size-dependent behavior supports the idea that forisome
      contractility might rest on similar mechanisms as those of polyelectrolyte gels,
      a class of artificial "smart" materials. In both species, time-courses of
      forisome length and diameter were variable and lacked correlation, arguing
      against a simple causal relationship between changes in length and width.
      Moreover, changes in the geometry of soybean forisomes differed qualitatively
      between Ca(2+)- and pH-responses, suggesting that divalent cations and protons
      target different sites on the forisome proteins.

PMID- 18330908
TI  - Negative influence of changing biopsy practice patterns on the predictive value
      of prostate-specific antigen for cancer detection on prostate biopsy.
AB  - BACKGROUND: A correlation between prostate specific antigen (PSA) level and
      positive prostate biopsy rate was established in an era when biopsy practice
      patterns were different from what they are today. We evaluated if changes in
      biopsy practice patterns have affected the ability of PSA to predict cancer
      detection on prostate biopsy in the current era. METHODS: Of 3634 prostate
      biopsies performed from 1993-2005, 1607 met criteria for analysis. Biopsy data
      were divided into 3 time-cohorts (1993-1997, 1998-2001, and 2002-2005) to assess
      for practice patterns shifts and correlation between PSA and biopsy results.
      RESULTS: Significant changes in biopsy practice patterns included an increase in
      biopsy cores and more frequent use of PSA 2.5-3.99 ng/mL as a biopsy indication.
      In men with normal DRE, a moderate correlation between PSA and positive biopsy
      rate did exist from 1993-1997, but was subsequently lost. On multivariate
      analysis, PSA was not a significant predictor of biopsy result in men with normal
      DRE. CONCLUSIONS: Early in the PSA era, the predictive power of PSA depended on
      multiple factors: high prevalence of disease, higher prevalence of high-grade
      disease, and low likelihood of prostate cancer diagnosis in men with low PSA.
      Now, beyond the culling effect of increased biopsy incidence and with shifted
      biopsy practice patterns, the correlation between PSA and biopsy result is lost
      in men with normal DRE. Diagnosing a higher proportion of tumors in men with a
      PSA between 2.0-4.0 ng/mL has negatively influenced the predictive value of PSA
      for cancer detection.

PMID- 18330909
TI  - Social class and workplace harassment during the transition to adulthood.
AB  - Young disadvantaged workers are especially vulnerable to harassment due to their
      age and social class position. As young people enter the workforce, their
      experiences of, and reactions to, harassment may vary dramatically from those of
      older adult workers. Three case studies introduce theory and research on the
      relationship between social class and harassment of young workers. We suggest two
      mechanisms through which class may structure harassment experiences: (1)
      extremely vulnerable youth are directly targeted based on their social class
      origins, and (2) the type and condition of youth employment, which is structured
      by class background, indirectly affect experiences of harassment.

PMID- 18330910
TI  - Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2,
      and MLH1 using zoom-in array comparative genomic hybridization (aCGH).
AB  - Disease-predisposing germline mutations in cancer susceptibility genes may
      consist of large genomic rearrangements that are challenging to detect and
      characterize using standard PCR-based mutation screening methods. Here, we
      describe a custom-made zoom-in microarray comparative genomic hybridization (CGH)
      platform of 60mer oligonucleotides. The 4 x 44 K array format provides high
      resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six
      cancer susceptibility genes. We evaluate its performance to accurately detect and
      precisely map earlier described or novel large germline deletions or duplications
      occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally,
      we demonstrate its applicability for uncovering complex somatic rearrangements,
      exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer
      cells. The sizes of rearrangements ranged from several 100 kb, including large
      flanking regions, to <500-bp deletions, including parts of single exons that
      would be missed by standard multiplex ligation-dependent probe amplification
      (MLPA) methods. Zoom-in CGH arrays accurately defined the borders of
      rearrangements, allowing convenient design of primers for sequence determination
      of the breakpoints. The array platform can be streamlined for a particular
      application, e.g., focusing on breast cancer susceptibility genes, with increased
      capacity using multiformat design, and represents a valuable new tool and
      complement for genetic screening in clinical diagnostics.

PMID- 18330911
TI  - SIX1 mutation screening in 247 branchio-oto-renal syndrome families: a recurrent
      missense mutation associated with BOR.
AB  - Branchio-oto-renal syndrome (BOR) is a clinically heterogeneous autosomal
      dominant form of syndromic hearing loss characterized by variable hearing
      impairment, malformations of the pinnae, the presence of branchial arch remnants,
      and various renal abnormalities. Both EYA1 and SIX1 are expressed in developing
      otic, branchial and renal tissue. Consistent with this expression pattern,
      mutations in both genes cause BOR syndrome. Mutations in EYA1 are found in
      approximately 40% of patients with the BOR phenotype, however, the role of SIX1
      is much lower. To date only three different SIX1 mutations have been described in
      BOR patients. The current screen of 247 BOR families detected five novel SIX1
      mutations (c.50T>A, c.218A>C, c.317T>G, c.329G>A, c.334C>T) and one previously
      reported mutation (c.328C>T) seen in 5 unrelated families. All mutations are
      within the protein-binding Six domain. Phenotypic variability was high in these
      BOR families. Seven of the eight known SIX1 mutations are missense and the one in
      frame deletion is predicted to be functionally similar. The wide phenotypic
      variability precludes making genotype-phenotype correlations at this time.

PMID- 18330912
TI  - PINK1 heterozygous rare variants: prevalence, significance and phenotypic
      spectrum.
AB  - Heterozygous rare variants in the PINK1 gene, as well as in other genes causing
      autosomal recessive parkinsonism, have been reported both in patients and healthy
      controls. Their pathogenic significance is uncertain, but they have been
      suggested to represent risk factors to develop Parkinson disease (PD). The few
      large studies that assessed the frequency of PINK1 heterozygotes in cases and
      controls yielded controversial results, and the phenotypic spectrum is largely
      unknown. We retrospectively analyzed the occurrence of PINK1 heterozygous rare
      variants in over 1100 sporadic and familial patients of all onset ages and in 400
      controls. Twenty patients and 6 controls were heterozygous, with frequencies
      (1.8% vs. 1.5%) not significantly different in the two groups. Clinical features
      of heterozygotes were indistinguishable to those of wild-type patients, with mean
      disease onset 10 years later than in carriers of two mutations but worse disease
      progression. A meta-analysis indicated that, in PINK1 heterozygotes, the PD risk
      is only slightly increased with a non significant odds ratio of 1.62. These
      findings suggest that PINK1 heterozygous rare variants play only a minor
      susceptibility role in the context of a multifactorial model of PD. Hence, their
      significance should be kept distinct from that of homozygous/compound
      heterozygous mutations, that cause parkinsonism inherited in a mendelian fashion.

PMID- 18330913
TI  - Intimate relationship development during the transition to adulthood: differences
      by social class.
AB  - This article examines differences in young adults' intimate relationships by
      social class. Lower-class adolescents are more likely to engage in intimate
      relationship practices such as cohabitation, early marriage, and sexual activity
      that may lead to further economic and educational deprivation. Such adolescents
      have limited access to the special opportunities of emerging adulthood. Social
      class indirectly shapes the relationships of groups such as prisoners, military
      personnel, and sexual minorities whose memberships are highly class graded and
      who are subject to state-controlled relationship constraints. More research is
      needed on how laws and institutions constrain even the most intimate features of
      young lives.

PMID- 18330914
TI  - Social class background and the school-to-work transition.
AB  - Whereas in years past, young people typically made a discrete transition from
      school to work, two ideal typical routes now characterize the sharing of school
      and work roles during adolescence and the transition to adulthood. Longitudinal
      data from the Youth Development Study show that one route involves less intensive
      employment during high school, followed by continued part-time employment and
      postsecondary educational investment. This pathway, more common for youth of
      higher-class origins, is especially beneficial for young people from lower
      socioeconomic backgrounds. A second route is early intensive work experience
      during high school that is less conducive to longer-term educational and wage
      attainments.

PMID- 18330915
TI  - Social class and the experience of work-family conflict during the transition to
      adulthood.
AB  - The challenges of juggling work and family responsibilities are well known, but
      there has been little attention to the distinctive work and family experiences of
      young adults. This chapter explores how class affects young adults' exposure to
      work-family conflicts and the strategies they use to manage their work and family
      responsibilities. Using data from a recent cohort of young adults, we find class
      and gender variations in work and family roles and work-family conflict. Early
      family formation, coupled with poor working conditions, lead those with lower
      educational attainments to experience more years of family-to-work interference.
      In contrast, young adults with more education have more work-to-family
      interference, and this is especially true for college-educated women.

PMID- 18330916
TI  - Family capital and the invisible transfer of privilege: intergenerational support
      and social class in early adulthood.
AB  - Sociologists have long recognized the relationships between family background and
      social class attainment. However, by neglecting the multiple ways in which
      families and parents provide advantages and the extent to which these advantages
      extend into adulthood, they may still be underestimating the role of families in
      the reproduction of class inequalities. This chapter explores these impacts under
      the conceptual rubric of family capital. A new battery of interviews with a
      diverse collection of young adults is used to illustrate these points and offer
      suggestions for future research and analysis.

PMID- 18330917
TI  - The intersections of social class and the transition to adulthood.
AB  - This article provides an introduction to and overview of the literature on how
      the transition to adulthood is shaped by social class. It brings together two
      strands of literature. The first reviews why and how the third decade of life has
      been reshaped by later and longer education. The second considers how the social
      class position of young adults influences their experience in the early adulthood
      years and how those experiences in turn affect their prospects in later life.

PMID- 18330918
TI  - Human genome variation and pharmacogenetics.
AB  - A recent HGVS-sponsored symposium has examined, for the first time, the possible
      effects of the discovery of very large and widespread amounts of human genome
      variation on the emerging fields of pharmacogenetics and pharmacogenomics. This
      article discusses the effects of the resultant paradigm shifts and raises a
      number of important questions that need to be considered in order to truly
      advance the field in a meaningful and significant way.

PMID- 18330919
TI  - PharmGKB and the International Warfarin Pharmacogenetics Consortium: the changing
      role for pharmacogenomic databases and single-drug pharmacogenetics.
AB  - PharmGKB, the pharmacogenetics and pharmacogenomics knowledge base
      (www.pharmgkb.org) is a publicly available online resource dedicated to the
      dissemination of how genetic variation leads to variation in drug responses. The
      goals of PharmGKB are to describe relationships between genes, drugs, and
      diseases, and to generate knowledge to catalyze pharmacogenetic and
      pharmacogenomic research. PharmGKB delivers knowledge in the form of curated
      literature annotations, drug pathway diagrams, and very important pharmacogene
      (VIP) summaries. Recently, PharmGKB has embraced a new role--broker of
      pharmacogenomic data for data sharing consortia. In particular, we have helped
      create the International Warfarin Pharmacogenetics Consortium (IWPC), which is
      devoted to pooling genotype and phenotype data relevant to the anticoagulant
      warfarin. PharmGKB has embraced the challenge of continuing to maintain its
      original mission while taking an active role in the formation of pharmacogenetic
      consortia.

PMID- 18330920
TI  - Discovery of genetic profiles impacting response to chemotherapy: application to
      gemcitabine.
AB  - Chemotherapy is a major treatment modality for individuals affected by cancer.
      Currently, a number of genome-based technologies are being adopted to identify
      genes associated with drug response; however, large-scale genetic association
      applications are still limited. Here we describe a novel strategy based on the
      genetic and drug response data of the NCI60 cell lines to discover potential
      candidate genetic variants associated with variable response to chemotherapy. As
      an example we have applied this strategy to discover single genetic markers and
      haplotypes from candidate genes previously implicated in the pharmacobiology of
      gemcitabine. Single-marker association analyses have implicated the association
      of four SNPs within the gene loci of CDC5L, EPC2, POLS, and PARP1. We have also
      investigated the combined effect of SNPs using haplotype-based analysis.
      Accordingly, we have shown modest association of haplotypes in six genes, whereas
      the most significant associations included a haplotype of the POLS gene. The
      hypothesis-generating tool presented in this study can be applied to drugs
      profiled in the NCI60 cell line screen and provides an effective means for the
      identification of genes associated with drug response. The results obtained using
      this novel methodology can be used to better design the clinical trials for
      effective study of the chemotherapeutic agents and thus provide a basis for
      individualized chemotherapy.

PMID- 18330921
TI  - Breaking barriers or locked out? Class-based perceptions and experiences of
      postsecondary education.
AB  - This article provides an overview of objective and subjective class differences
      in experiences of postsecondary education. Using the metaphor of a funnel, it
      argues that cumulative disadvantage results when first-generation and low-income
      college students are disproportionately filtered out at each stage of the
      postsecondary education process. Subjective class differences largely serve to
      reproduce existing inequalities, although the potential for transformation
      exists. This article considers inequalities during childhood and the transition
      to adulthood, stratification within institutions, and class differences in
      postsecondary educational enrollment, attendance, college life, work, financial
      aid, and attainment. Directions for future research and program and policy
      interventions are outlined.

PMID- 18330922
TI  - Patterns of intraneural ganglion cyst descent.
AB  - On the basis of the principles of the unifying articular theory, predictable
      patterns of proximal ascent have been described for fibular (peroneal) and tibial
      intraneural ganglion cysts in the knee region. The mechanism underlying distal
      descent into the terminal branches of the fibular and tibial nerves has not been
      previously elucidated. The purpose of this study was to demonstrate if and when
      cyst descent distal to the articular branch-joint connection occurs in
      intraneural ganglion cysts to understand directionality of intraneural cyst
      propagation. In Part I, the clinical records and MRIs of 20 consecutive patients
      treated at our institution for intraneural ganglion cysts (18 fibular and two
      tibial) arising from the superior tibiofibular joint were retrospectively
      analyzed. These patients underwent cyst decompression and disconnection of the
      articular branch. Five of these patients developed symptomatic cyst recurrence
      after cyst decompression without articular branch disconnection which was done
      elsewhere prior to our intervention. In Part II, five additional patients with
      intraneural ganglion cysts (three fibular and two tibial) treated at other
      institutions without disconnection of the articular branch were compared. These
      patients in Parts I and II demonstrated ascent of intraneural cyst to differing
      degrees (12 had evidence of sciatic nerve cross-over). In addition, all of these
      patients demonstrated previously unrecognized MRI evidence of intraneural cyst
      extending distally below the level of the articular branch to the joint of
      origin: cyst within the proximal most portions of the deep fibular and
      superficial fibular branches in fibular intraneural ganglion cysts and descending
      tibial branches in tibial intraneural ganglion cysts. The patients in Part I had
      complete resolution of their cysts at follow-up MRI examination 1 year
      postoperatively. The patients in Part II had intraneural recurrences
      postoperatively within the articular branch, the parent nerve, and the terminal
      branches, although in three cases they were subclinical. The authors demonstrate
      that cyst descent distal to the take-off of the articular branch to the joint of
      origin occurs regularly in patients with fibular and tibial intraneural ganglion
      cysts. The authors believe that parent terminal branch descent follows ascent up
      the articular branch from an affected joint of origin. This mechanism for
      bidirectional flow explains cyst within terminal branches of the fibular and
      tibial nerves and is dependent on pressure fluxes and resistances. This new
      pattern is consistent with principles previously described in a unified
      (articular) theory, is generalizable to other intraneural ganglion cysts arising
      from joints, and has important implications for pathogenesis and treatment of
      these intraneural cysts.

PMID- 18330923
TI  - Ontogeny of vasotocin-expressing cells in zebrafish: selective requirement for
      the transcriptional regulators orthopedia and single-minded 1 in the preoptic
      area.
AB  - The neurohypophysial peptide arginine vasotocin, and its mammalian ortholog
      arginine vasopressin, influence a wide range of physiological and behavioral
      responses, including aspects of sexual and social behaviors, osmoregulation,
      stress response, metabolism, blood pressure, and circadian rhythms. Here, we
      demonstrate that, in zebrafish (Danio rerio), the vasotocin precursor gene
      arginine vasotocin-neurophysin (avt) is expressed in two domains in the
      developing embryo: the dorsal preoptic area and the ventral hypothalamus. In the
      dorsal preoptic area, avt-expressing cells are intermingled with isotocin
      neurophysin (ist) -expressing cells, and these neurons project to the
      neurohypophysis (posterior pituitary). In the dorsal preoptic area, the
      transcriptional regulators orthopedia b (otpb) and simple-minded 1 (sim1) are
      required for expression of both avt and ist. In contrast, otp and sim1 are not
      required for avt expression in the ventral hypothalamus. Thus, the development of
      these two avt expression domains is influenced by separate gene regulatory
      networks.

PMID- 18330924
TI  - Different effects of anti-sonic hedgehog antibodies and the hedgehog pathway
      inhibitor cyclopamine on generation of dopaminergic neurons from neurospheres of
      mesencephalic precursors.
AB  - Production of dopaminergic neurons from stem/precursor cells for transplantation
      in Parkinson's disease has become a major focus of research. However, the
      inductive signals mediating this process have not been clarified. Reported data
      on the effects of Sonic hedgehog on differentiation of dopaminergic and
      serotonergic neurons from cultures of neural precursors are controversial. In the
      present study, cultures of proliferating neurospheres of mesencephalic precursors
      treated with anti-sonic hedgehog antibodies showed significantly less
      serotonergic and GABAergic cells and a markedly higher number of dopaminergic
      neurons generated from the neurospheres than control cultures. Treatment of the
      neurospheres with cyclopamine, which selectively inhibits sonic hedgehog
      signaling by preventing Smoothened activation, did not induce significant changes
      in generation of serotonergic and dopaminergic neurons. This suggests that
      Smoothened activation is not significantly involved in the above-mentioned
      effects and that sonic hedgehog may exert effects on the mesencephalic precursors
      that do not involve the canonical Patched-Smoothened-Gli signaling.

PMID- 18330925
TI  - Differences in early lineage segregation between mammals.
AB  - Two lineage segregation events in mammalian development form the trophectoderm,
      primitive endoderm, and pluripotent primitive ectoderm. In mouse embryos, Oct4,
      Cdx2, Nanog, and Gata6 govern these events, but it is unknown whether this is
      conserved between mammals. Here, the expression patterns of these genes and their
      products were determined in porcine oocytes and embryos and in bovine embryos.
      CDX2 and GATA6 expression in porcine and bovine blastocysts resembled that of
      mouse, indicating conserved functions. However, NANOG expression was undetectable
      in porcine oocytes and embryos. Some inner cell mass cells in bovine blastocysts
      expressed NANOG protein. OCT4 protein was undetectable in porcine morulae, but
      present in both the trophectoderm and the inner cell mass of blastocysts,
      suggesting that downregulation of OCT4 in the trophectoderm does not precede
      trophectoderm formation. Combined, the results indicate differences in lineage
      segregation between mammals.

PMID- 18330926
TI  - Proper expression of the Gcn5 histone acetyltransferase is required for neural
      tube closure in mouse embryos.
AB  - Histone acetyltransferases (HATs) are important to gene activation, altering
      chromatin structures to facilitate association of transcription proteins with
      gene promoters. The functions of individual HATs in mammalian developmental are
      not well defined. Our previous studies demonstrated that Gcn5, a prototypical
      HAT, is required for mesodermal maintenance in early embryos. Homozygous Gcn5
      null embryos die soon after gastrulation, preventing determination of Gcn5
      functions later during development. We report here the creation of a
      Gcn5(flox(neo)) allele, which is only partially functional and gives rise to a
      hypomorphic phenotype. Mice homozygous for this allele had an increased risk of
      cranial neural tube closure defects (NTDs) and exencephaly. These defects were
      found at an even greater penetrance in Gcn5(flox(neo)/Delta) embryos. These
      results indicate that normal levels of Gcn5 expression are critical for neural
      tube closure in mice and predict that mutations in this HAT may be associated
      with increased risk of NTDs in humans.

PMID- 18330927
TI  - Notch2 is required for the proliferation of cardiac neural crest-derived smooth
      muscle cells.
AB  - Mutations in Notch receptors and their ligands have been identified as the cause
      of human congenital heart diseases, indicating the importance of the Notch
      signaling pathway during heart development. In our study, we use Cre-Lox
      technology to inactivate Notch2 in several cardiac cell lineages to determine the
      functional requirements for Notch2 during mammalian heart development.
      Inactivation of Notch2 in cardiac neural crest cells resulted in abnormally
      narrow aortas and pulmonary arteries due to a decrease in smooth muscle tissue.
      The reduction in smooth muscle tissue was not due to cell migration defects but
      instead was found to be caused by less proliferation in smooth muscle cells
      during mid to late gestation. Our findings demonstrate that Notch2 is required
      cell autonomously for proper formation of the heart outflow tract and provides
      insights into the role of Notch2 in vascular smooth muscle development and the
      cardiovascular defects associated with Alagille syndrome.

PMID- 18330928
TI  - Primary cilia in osteoarthritic chondrocytes: from chondrons to clusters.
AB  - Osteoarthritis (OA) is a common joint disease characterized by articular
      cartilage degeneration. The etiology of OA is unknown. Because several previous
      studies have shown that primary cilia play critical roles in joint development,
      this study examined the incidence and morphology of primary cilia in chondrocytes
      during joint degeneration in a naturally occurring bovine model of OA. Primary
      cilia were detected using antibodies to acetylated alpha-tubulin in normal
      cartilage as well as in mild and severe OA tissue. In normal cartilage, cilia
      number and length were lowest in the superficial zone and increased with distance
      from the articular surface. In OA tissue, the incidence and length of cilia
      increased at the eroding articulating surface, resulting in an overall increased
      proportion of cilia. This is the first study to show that primary cilia are
      present on chondrocytes throughout OA progression and that the overall percentage
      of ciliated cells within the degenerating cartilage increases with OA severity.

PMID- 18330930
TI  - Current perspectives in zebrafish reverse genetics: moving forward.
AB  - Use of the zebrafish as a model of vertebrate development and disease has
      expanded dramatically over the past decade. While many articles have discussed
      the strengths of zebrafish forward genetics (the phenotype-driven approach),
      there has been less emphasis on equally important and frequently used reverse
      genetics (the candidate gene-driven approach). Here we review both current and
      prospective reverse genetic techniques that are applicable to the zebrafish
      model. We include discussion of pharmacological approaches, popular gain-of
      function and knockdown approaches, and gene targeting strategies. We consider the
      need for temporal and spatial control over gain/loss of gene function, and
      discuss available and developing techniques to achieve this end. Our goal is both
      to reveal the current technical advantages of the zebrafish and to highlight
      those areas where work is still required to allow this system to be exploited to
      full advantage.

PMID- 18330929
TI  - The transmembrane inner ear (tmie) gene contributes to vestibular and lateral
      line development and function in the zebrafish (Danio rerio).
AB  - The inner ear is a complex organ containing sensory tissue, including hair cells,
      the development of which is not well understood. Our long-term goal is to
      discover genes critical for the correct formation and function of the inner ear
      and its sensory tissue. A novel gene, transmembrane inner ear (Tmie), was found
      to cause hearing-related disorders when defective in mice and humans. A
      homologous tmie gene in zebrafish was cloned and its expression characterized
      between 24 and 51 hours post-fertilization. Embryos injected with morpholinos
      (MO) directed against tmie exhibited circling swimming behavior (approximately
      37%), phenocopying mice with Tmie mutations; semicircular canal formation was
      disrupted, hair cell numbers were reduced, and maturation of electrically active
      lateral line neuromasts was delayed. As in the mouse, tmie appears to be required
      for inner ear development and function in the zebrafish and for hair cell
      maturation in the vestibular and lateral line systems as well.

PMID- 18330931
TI  - High-resolution in vivo imaging of the cross-sectional deformations of
      contracting embryonic heart loops using optical coherence tomography.
AB  - The embryonic heart tube consists of an outer myocardial tube, a middle layer of
      cardiac jelly, and an inner endocardial tube. It is said that tubular hearts pump
      the blood by peristaltoid contractions. The traditional concept of cardiac
      peristalsis sees the cyclic deformations of pulsating heart tubes as concentric
      narrowing and widening of tubes of circular cross-section. We have visualized the
      cross-sectional deformations of contracting embryonic hearts in chick embryos (HH
      stages 9-17) using real-time high-resolution optical coherence tomography.
      Cardiac contractions are detected from HH-stage 10 onward. During the cardiac
      cycle, the myocardial tube undergoes concentric narrowing and widening while the
      endocardial tube undergoes eccentric narrowing and widening, having an elliptic
      cross-section at end-diastole and a slit-shaped cross-section at end-systole. The
      eccentric deformation of the endocardial tube is the consequence of an uneven
      distribution of the cardiac jelly. Our data show that the cyclic deformations of
      pulsating embryonic heart tubes run other than originally thought. There is
      evidence that heart tubes of elliptic cross-section might pump blood with a
      higher mechanical efficiency than those of circular-cross section. The uneven
      distribution of cardiac jelly seems to prefigure the future AV and cono-truncal
      endocardial cushions.

PMID- 18330932
TI  - RNA expression microarray analysis in mouse prospermatogonia: identification of
      candidate epigenetic modifiers.
AB  - The mammalian totipotent and pluripotent lineage exhibits genome-wide dynamics
      with respect to DNA methylation content. The first phase of global DNA
      demethylation and de novo remethylation occurs during preimplantation development
      and gastrulation, respectively, while the second phase occurs in primordial germ
      cells and primary oocytes/prospermatogonia, respectively. These dynamics are
      indicative of a comprehensive epigenetic resetting or reprogramming of the genome
      in preparation for major differentiation events. To gain further insight into the
      mechanisms driving DNA methylation dynamics and other types of epigenetic
      modification, we performed an RNA expression microarray analysis of fetal
      prospermatogonia at the stage when they are undergoing rapid de novo DNA
      remethylation. We have identified a number of highly or specifically expressed
      genes that could be important for determining epigenetic change in
      prospermatogonia. These data provide a useful resource in the discovery of
      molecular pathways involved in epigenetic reprogramming in the mammalian germ
      line.

PMID- 18330933
TI  - In vitro characterization of phosphatidylglyceroglycerol-based thermosensitive
      liposomes with encapsulated 1H MR T1-shortening gadodiamide.
AB  - Thermosensitive liposomes (TSL) with encapsulated proton (1H) magnetic resonance
      (MR) contrast agents have been proposed for noninvasive online temperature
      monitoring during tumor treatment using chemotherapy combined with hyperthermia
      (HT). The technique exploits the fact that water exchange between the TSL
      interior and exterior is increased and/or the encapsulated 1H MR contrast agent
      is released near the gel-to-liquid crystalline phase transition temperature (Tm)
      of TSL and thus shortens the 1H MR relaxation time of tissue. In this work, newly
      developed, phosphatidylglyceroglycerol (DPPGOG)-based TSL with encapsulated 1H MR
      longitudinal relaxation time (T1)-shortening gadodiamide (Gd-DTPA-BMA) were
      characterized in vitro by measuring the temperature dependence of the T1 of these
      gadodiamide-containing DPPGOG-TSL samples between 30 and 50 degrees C. The
      measurements revealed that the T1 nonlinearly slightly decreased with increasing
      temperature from 30 to 37 degrees C, mainly due to increased water exchange
      between the gadodiamide-containing DPPGOG-TSL interior and exterior with the
      exception of negligible gadodiamide release. This implies that gadodiamide
      containing DPPGOG-TSL were stable at temperatures < or =37 degrees C, which was
      also confirmed by an independent stability study. From 37 to 44 degrees C, the T1
      nonlinearly markedly decreased with increasing temperature since encapsulated
      gadodiamide was rapidly released. Above 44 degrees C, gadodiamide was completely
      released and the T1 was directly proportional to temperature while heated from 44
      to 50 degrees C and cooled from 50 to 30 degrees C, respectively. Additionally,
      gadodiamide release was theoretically quantified and this calculated
      concentration was consistent with the actually released amount directly obtained
      from the cooling course of empty DPPGOG-TSL with completely released gadodiamide.

PMID- 18330934
TI  - H pylori recurrence after successful eradication.
AB  - Recurrence of H pylori after eradication is rare in developed countries and more
      frequent in developing countries. Recrudescence (recolonization of the same
      strain within 12 mo after eradication) rather than reinfection (colonization with
      a new strain, more than 12 mo after eradication) is considered to be responsible
      for most of the cases. This observation was confirmed only in developed
      countries, while in developing countries a recent meta-analysis demonstrated a
      high rate of reinfection. The proportion of H pylori annual recurrence was 2.67%
      and 13.00% in developed and developing countries, respectively. Nested meta
      analysis (only cases with a longer follow-up and a negative (13)CUBT a year after
      eradication) revealed annual recurrence rate of 1.45% [relative risk (RR), 0.54]
      and 12.00% (RR, 0.92) in developed and developing countries, respectively. These
      findings support the notion that in developed countries many cases of recurrence
      are due to recrudescence within the first year after eradication, with a 46% drop
      in the recurrence rate after the first year post eradication, while in developing
      countries reinfection is more pronounced, and continue at the same rate since
      eradication. A different approach for follow-up after H pylori eradication is
      probably needed in patients of developing countries, since reinfection is highly
      prevalent.

PMID- 18330935
TI  - Staging accuracy of esophageal cancer by endoscopic ultrasound: a meta-analysis
      and systematic review.
AB  - AIM: To evaluate the accuracy of endoscopic ultrasound (EUS) in the staging of
      esophageal cancer. METHODS: Only EUS studies confirmed by surgery were selected.
      Articles were searched in Medline and Pubmed. Two reviewers independently
      searched and extracted data. Meta-analysis of the accuracy of EUS was analyzed by
      calculating pooled estimates of sensitivity, specificity, likelihood ratios, and
      diagnostic odds ratio. Pooling was conducted by both the Mantel-Haenszel method
      (fixed effects model) and DerSimonian Laird method (random effects model). The
      heterogeneity of studies was tested using Cochran's Q test based upon inverse
      variance weights. RESULTS: Forty-nine studies (n = 2558) which met the inclusion
      criteria were included in this analysis. Pooled sensitivity and specificity of
      EUS to diagnose T1 was 81.6% (95% CI: 77.8-84.9) and 99.4% (95% CI: 99.0-99.7),
      respectively. To diagnose T4, EUS had a pooled sensitivity of 92.4% (95% CI: 89.2
      95.0) and specificity of 97.4% (95% CI: 96.6-98.0). With Fine Needle Aspiration
      (FNA), sensitivity of EUS to diagnose N stage improved from 84.7% (95% CI: 82.9
      86.4) to 96.7% (95% CI: 92.4-98.9). The P value for the c2 test of heterogeneity
      for all pooled estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity
      and specificity in accurately diagnosing the TN stage of esophageal cancer. EUS
      performs better with advanced (T4) than early (T1) disease. FNA substantially
      improves the sensitivity and specificity of EUS in evaluating N stage disease.
      EUS should be strongly considered for staging esophageal cancer.

PMID- 18330936
TI  - Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia
      bellerica extracts with conventional cytotoxic agents: doxorubicin and cisplatin
      against human hepatocellular carcinoma and lung cancer cells.
AB  - AIM: To examine the growth inhibitory effects of Phyllanthus emblica (P. emblica)
      and Terminalia bellerica (T. bellerica) extracts on human hepatocellular
      carcinoma (HepG2), and lung carcinoma (A549) cells and their synergistic effect
      with doxorubicin or cisplatin. METHODS: HepG2 and A549 cells were treated with P.
      emblica and T. bellerica extracts either alone or in combination with doxorubicin
      or cisplatin and effects on cell growth were determined using the sulforhodamine
      B (SRB) assay. The isobologram and combination index (CI) method of Chou-Talalay
      were used to evaluate interactions between plant extracts and drugs. RESULTS: P.
      emblica and T. bellerica extracts demonstrated growth inhibitory activity, with a
      certain degree of selectivity against the two cancer cell lines tested.
      Synergistic effects (CI < 1) for P. emblica/doxorubicin or cisplatin at different
      dose levels were demonstrated in A549 and HepG2 cells. The T. bellerica/cisplatin
      or doxorubicin also showed synergistic effects in A549 and HepG2 cells. In some
      instances, the combinations resulted in antagonistic effects. The dose reduction
      level was different and specific to each combination and cell line. CONCLUSION:
      The growth inhibitory activity of doxorubicin or cisplatin, as a single agent,
      may be modified by combinations of P. emblica or T. bellerica extracts and be
      synergistically enhanced in some cases. Depending on the combination ratio, the
      doses for each drug for a given degree of effect in the combination may be
      reduced. The mechanisms involved in this interaction between chemotherapeutic
      drugs and plant extracts remain unclear and should be further evaluated.

PMID- 18330937
TI  - Polymorphism of -765G > C COX-2 is a risk factor for gastric adenocarcinoma and
      peptic ulcer disease in addition to H pylori infection: a study from northern
      India.
AB  - AIM: To investigate -765G > C COX-2 polymorphism and H pylori infection in
      patients with gastric adenocarcinoma, peptic ulcer disease (PUD) and non-ulcer
      dyspepsia (NUD). METHODS: We enrolled 348 adult patients (62 gastric
      adenocarcinoma, 45 PUD and 241 NUD) undergoing upper gastrointestinal endoscopy
      at two referral centers between September, 2002 and May, 2007. H pylori infection
      was diagnosed when any of the four tests (RUT, culture, histopathology and PCR)
      were positive. Genotyping for -765G > C polymorphism of COX-2 was performed by
      PCR-RFLP analysis. RESULTS: Frequency of C carrier had significant association
      with gastric adenocarcinoma as compared to NUD [77.4% vs 29%, P < 0.001, odds
      ratio (OR) 8.20; 95% confidence interval (95% CI), 4.08-16.47] and PUD (77.4% vs
      31.1%, P < 0.001; OR 8.04; 95% CI, 3.25-19.90). Risk of gastric adenocarcinoma
      was significantly higher in patients having C carrier with (OR 7.83; 95% CI 3.09
      19.85) and without H pylori infection (OR 7.06; 95% CI, 2.61-19.09). Patients
      with C carrier and H pylori infection had significant risk for the development of
      PUD (P < 0.001; OR 5.65; 95% CI, 2.07-15.34). CONCLUSION: -765G > C COX-2
      polymorphism with or without H pylori could be a marker for genetic
      susceptibility to gastric adenocarcinoma. COX-2 polymorphism in presence of H
      pylori infection might be useful in predicting the risk of PUD.

PMID- 18330938
TI  - Apoptosis of human pancreatic cancer cells induced by Triptolide.
AB  - AIM: To investigate apoptosis in human pancreatic cancer cells induced by
      Triptolide (TL), and the relationship between this apoptosis and expression of
      caspase-3' bcl-2 and bax. METHODS: Human pancreatic cancer cell line SW1990 was
      cultured in DMEM media for this study. MTT assay was used to determine the cell
      growth inhibitory rate in vitro. Flow cytometry and TUNEL assay were used to
      detect the apoptosis of human pancreatic cancer cells before and after TL
      treatment. RT-PCR was used to detect the expression of apoptosis-associated gene
      caspase-3' bcl-2 and bax. RESULTS: TL inhibited the growth of human pancreatic
      cancer cells in a dose-and time-dependent manner. TL induced human pancreatic
      cancer cells to undergo apoptosis with typically apoptotic characteristics. TUNEL
      assay showed that after the treatment of human pancreatic cancer cells with 40
      ng/mL TL for 12 h and 24 h, the apoptotic rates of human pancreatic cancer cells
      increased significantly. RT-PCR demonstrated that caspase-3 and bax were
      significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was
      not. CONCLUSION: TL is able to induce the apoptosis in human pancreatic cancer
      cells. This apoptosis may be mediated by up-regulating the expression of
      apoptosis-associated caspase-3 and bax gene.

PMID- 18330939
TI  - Hepatitis B virus genotypes in southwest Iran: molecular, serological and
      clinical outcomes.
AB  - AIM: To investigate the associations of hepatitis B virus (HBV) genotype with
      HBeAg and anti-HBe status, alanine aminotransferase (ALT) levels and HBV-DNA
      detection in different groups of HBV-infected patients in southwest Iran.
      METHODS: A total of 89 HBsAg-positive serum samples were collected from the same
      number of patients. All sera were then investigated to determine HBV DNA and
      serological markers. For all the polymerase chain reaction (PCR)-positive
      samples, biochemical, histopathological assays and genotyping were also
      performed. RESULTS: Genotype D was the only type of HBV found in different
      clinical forms of acute and chronic infections. There was a high prevalence of
      HBeAg-negative HBV-infected patients with chronic hepatitis (52.7%). Out of 55
      patients with chronic hepatitis, seven (12.7%) were diagnosed with cirrhosis. A
      significant association between the presence of anti-HBe antibody and an increase
      in ALT level, among either HBeAg-negative (P = 0.01) or HBeAg-positive (P =
      0.026) patients, was demonstrated. No significant differences were observed
      between the clinical outcomes of HBeAg-positive and -negative individuals (P =
      0.24). CONCLUSION: Genotype D has been recognized as the only type of HBV found
      in different clinical forms of HBV infections, including cirrhosis, among the
      residents of southwest Iran. Anti-HBe possibly plays a role in disease
      progression in some patients with chronic hepatitis, at least for a period of
      disease.

PMID- 18330940
TI  - Transnasal endoscopic retrograde chalangiopancreatography using an ultrathin
      endoscope: a prospective comparison with a routine oral procedure.
AB  - AIM: To investigate if transnasal endoscopic retrograde cholangiopancreatography
      (n-ERCP) using an ultrathin forward-viewing scope may overcome the disadvantages
      of conventional oral ERCP (o-ERCP) related to the large-caliber side-viewing
      duodenoscope. METHODS: The study involved 50 patients in whom 25 cases each were
      assigned to the o-ERCP and n-ERCP groups. We compared the requirements of
      esophagogastroduodenoscopy (EGD) prior to ERCP, rates and times required for
      successful cannulation into the pancreatobiliary ducts, incidence of post
      procedure hyperamylasemia, cardiovascular parameters during the procedure, the
      dose of a sedative drug, and successful rates of endoscopic naso-biliary drainage
      (ENBD). RESULTS: Screening gastrointestinal observations were easily performed by
      the forward-viewing scope and thus no prior EGD was required in the n-ERCP group.
      There was no significant difference in the rates or times for cannulation, or
      incidence of hyperamylasemia between the groups. However, the cannulation was
      relatively difficult in n-ERCP when the scope appeared U-shape under fluoroscopy.
      Increments of blood pressure and the amount of a sedative drug were significantly
      lower in the n-ERCP group. ENBD was successfully performed succeeding to the n
      ERCP in which mouth-to-nose transfer of the drainage tube was not required.
      CONCLUSION: n-ERCP is likely a well-tolerable method with less cardiovascular
      stress and no need of prior EGD or mouth-to-nose transfer of the ENBD tube.
      However, a deliberate application is needed since its performance is difficult in
      some cases and is not feasible for some endoscopic treatments such as stenting.

PMID- 18330941
TI  - Regulatory T cells in patients with inflammatory bowel diseases treated with
      adacolumn granulocytapheresis.
AB  - AIM: To investigate if the clinical efficacy of granulocytes and monocytes by
      adsorption (GMA) is associated with an increased frequency of peripheral
      regulatory T cells (Tregs), as these cells have proven to be successful in
      suppressing inflammatory bowel disease (IBD) in animal models. METHODS: We report
      four cases of corticosteroid-dependent ulcerative colitis (UC) and two Crohn's
      disease (CD) cases with severe cutaneous lesions who received GMA therapy. The
      frequency of CD4+ CD25(high) (Tregs) in peripheral blood was analyzed by flow
      cytometry and the expression of FoxP3 and TGF beta in purified CD4+ T cells was
      determined by real time PCR prior to and one month after the last apheresis
      session, and at the time of endoscopic and clinical assessing. RESULTS: Increased
      expression of Fox P3 mRNA was found in all five patients who responded to
      cytapheresis with remission of clinical symptoms, mucosal inflammation and
      cutaneous lesions, and an increased frequency of circulating Tregs was found in
      four patients. These changes were not observed in the patient with UC who did no
      respond to GMA. Variations in TGF-beta (mRNA) did not parallel that of FoxP3
      mRNA. CONCLUSION: The clinical efficacy of GMA on IBD and related extra
      intestinal manifestations was associated with an expansion of circulating CD4+
      CD25+ Tregs and higher expression of FoxP3 in CD4+ T cells. Accordingly, an
      elevated CD4+ CD25+ FoxP3 may be a valuable index of remission in patients with
      IBD and other chronic relapsing-remitting inflammatory conditions during
      treatment with GMA.

PMID- 18330942
TI  - Increased basolateral sorting of carcinoembryonic antigen in a polarized colon
      carcinoma cell line after cholesterol depletion-Implications for treatment of
      inflammatory bowel disease.
AB  - AIM: To investigate a possible increase of basolateral expression of
      carcinoembryonic antigen (CEA) by interfering with the apical transport
      machinery, we studied the effect of cholesterol depletion on CEA sorting and
      secretion. METHODS: Cholesterol depletion was performed in polarized Caco-2 cells
      using lovastatin and methyl-beta-cyclodextrin. RESULTS: We show that CEA is
      predominantly expressed and secreted at the apical surface. Reduction of the
      cholesterol level of the cell by 40%-50% with lovastatin and methyl-beta
      cyclodextrin led to a significant change of the apical-to-basolateral transport
      ratio towards the basolateral membrane. CONCLUSION: As basolateral expression of
      CEA has been suggested to have anti-inflamatory properties, Cholesterol depletion
      of enterocytes might be a potential approach to influence the course of
      inflammatory bowel disease.

PMID- 18330943
TI  - Clinical predictors of colorectal polyps and carcinoma in a low prevalence
      region: results of a colonoscopy based study.
AB  - AIM: To estimate the prevalence of colorectal cancer (CRC) in patients with long
      lasting colonic symptoms undergoing total colonoscopy; and to establish clinical
      features predicting its occurrence. METHODS: This prospective study was carried
      out in Imam Hospital, Tabriz University of medical sciences, Iran. Continuous
      patients with long lasting lower gastrointestinal tract symptoms who had the
      criteria of a colonoscopy were included. The endoscopist visualized the caecum
      documented by a photo and/or a specimen from terminal ileum. RESULTS: Four
      hundred and eighty consecutive symptomatic patients [mean age (SD): 42.73
      (16.21)] were included. The prevalence of colorectal neoplasia was 15.3% (34
      subjects) and 37.7% (181 subjects) had a completely normal colon. Adenomatous
      polyps were detected in 56 (11.7%) patients, in 12.3% of men and 10.9% of women.
      The mean age of the patients with a polyp was significantly higher than the
      others (49.53 +/- 14.16 vs 41.85 +/- 16.26, P = 0.001). Most of the adenomatous
      polyps were left sided and tubular; only 22.5% of polyps were more than 10 mm.
      Cancer was detected in 16 (3.6%) of our study population, which was mostly right
      sided (57.2%). The mean age of patients with cancer was significantly higher than
      the others (60.25 +/- 8.26 vs 42.13 +/- 16.08, P < 0.005) and higher than
      patients with polyps [60.25 (8.26) vs 49.53 (1.91) (P < 0.0005)]. None of the
      symptoms (diarrhea, abdominal pain, rectal bleeding, constipation, altering
      diarrhea and constipation, history of cancer, known irritable bowel disease,
      history of polyp and fissure or family history of cancer) were predictors for
      cancer or polyps, but the age of the patient and unexplained anemia independently
      predicted cancer. CONCLUSION: Less advanced patterns and smaller sizes of
      adenomas in Iran is compatible with other data from Asia and the Middle East, but
      in contrast to western countries. Prevalence of colonic neoplasia in our
      community seems to be lower than that in western population. Colonic symptoms are
      not predictors for polyps or cancer but unexplained anemia and elder age can
      predict CRC.

PMID- 18330944
TI  - Gastric juice for the diagnosis of H pylori infection in patients on proton pump
      inhibitors.
AB  - AIM: To determine the efficacy of gastric juice polymerase chain reaction (PCR)
      for the detection of H pylori infection in comparison with histology and gastric
      antral biopsy PCR in patients on a proton pump inhibitor (PPI). METHODS: Eighty
      five consecutive patients with dyspeptic symptoms were enrolled. Gastric biopsies
      for histology, PCR and gastric juice were collected at endoscopy for PCR of the H
      pylori urease C gene (ure C). Sensitivity, specificity, positive predictive value
      (PPV), negative predictive value (NPV), accuracy, positive and negative
      likelihood ratio for PCR of gastric juice for the H pylori ure C gene was
      compared to histology and gastric antral biopsy H pylori ure C PCR in patients
      with and without PPI. RESULTS: Gastric juice PCR was positive in 66 (78%)
      patients. Histology showed H pylori associated gastritis in 57 (67%). Gastric
      biopsy PCR was positive in 72 (85%). In patients not taking PPI, the sensitivity,
      specificity, PPV, NPV, accuracy and positive and negative likelihood ratio for
      gastric juice PCR were 89%, 72%, 91%, 67%, 90%, 85%, 3.1 and 0.1 respectively. In
      patients on PPI these values were 86%, 100%%, 100%, 29%, 86%, 9.5 and 1.4,
      respectively. CONCLUSION: Gastric juice PCR for the diagnosis of H pylori
      infection has increased sensitivity compared to histology with PPI. The use of
      gastric juice PCR is recommended to confirm H pylori status in patients taking
      PPIs.

PMID- 18330945
TI  - High rate of complicated idiopathic gallstone disease in pediatric patients of a
      North American tertiary care center.
AB  - AIM: To assess spectrum and etiology of gallstones and biliary sludge in the
      pediatric population of a North American tertiary care centre. METHODS:
      Retrospective review of abdominal ultrasounds recorded at Saint Justine Hospital
      over a period of 24 mo (8/2003 to 8/2005) in patients < 19 years of age. Patients
      < 2 years of age were analyzed separately. RESULTS: The presence of gallstones
      was noted in 127 patients. In 107 it was a new diagnosis, in 48/105 (45.7%)
      patients > 2 years of age idiopathic gallstone disease was found. These 48
      patients represent 2.1% of the population who required ultrasound for abdominal
      pain. Complicated gallstone disease occurred in 28/48 with idiopathic disease,
      mainly adolescent girls. Patients with hemolytic disorders, cystic fibrosis,
      oncologic diseases or kidney transplantation and gallstones were asymptomatic and
      stones were detected during routine abdominal ultrasound. Twenty two patients < 2
      years of age not consulting for abdominal pain had gallstone disease of diverse
      etiology. Biliary sludge was seen in 84 patients, 78.5% on total parenteral
      nutrition. In 4 patients, sludge progressed to gallstones. CONCLUSION: Idiopathic
      gallstone disease and its rate of complication are more frequent in our cohort
      than expected from previous studies. Adolescent girls with abdominal pain and
      idiopathic gallstones require special attention for complicated disease course.

PMID- 18330946
TI  - High circulating D-dimers are associated with ascites and hepatocellular
      carcinoma in liver cirrhosis.
AB  - AIM: To measure plasma D-dimer levels in cirrhotic patients with and without
      ascites, assessing the effect of ascites resolution in D-dimer concentration.
      METHODS: Seventy consecutive cirrhotic patients (M = 44, F = 26, mean age 65
      years, SD +/- 13), observed from October 2005 to March 2006 were enrolled.
      Circulating D-dimer levels were measured using a latex-enhanced,
      immunoturbidimetric test. In patients with ascites (n = 42) the test was repeated
      after ascites resolution. RESULTS: Ascites was present in 42 patients (group A)
      and absent in 28 (group B). Group A patients had more advanced liver disease.
      Hepatocellular carcinoma (HCC) was diagnosed in 14 patients and was more frequent
      in group B. Above normal range D-dimers were found in 45/70 patients. High D
      dimers were more frequent in group A than in group B (P = 0.001). High D-dimers
      were associated with presence of HCC (P = 0.048) only in group B. After ascites
      resolution, obtained in all patients, mean D-dimer values decreased in those 34
      patients with high basal levels (P = 0.007), returning to normal in 17.
      CONCLUSION: In patients with liver cirrhosis, ascites and HCC are the main
      factors associated with increased fibrinolytic activity.

PMID- 18330947
TI  - Impact of obesity on the surgical outcome following repeat hepatic resection in
      Japanese patients with recurrent hepatocellular carcinoma.
AB  - AIM: To evaluate the impact of obesity on the posto-perative outcome after
      hepatic resection in patients with hepatocellular carcinoma (HCC). METHODS: Data
      from 328 consecutive patients with primary HCC and 60 patients with recurrent HCC
      were studied. We compared the surgical outcomes between the non-obese group (body
      mass index: BMI < 25 kg/m(2)) and the obese group (BMI > or = 25 kg/m(2)).
      RESULTS: Following curative hepatectomy in patients with primary HCC, the
      incidence of postoperative complications and the long-term prognosis in the non
      obese group (n = 240) were comparable to those in the obese group (n = 88). Among
      patients with recurrent HCC, the incidence of postoperative complications after
      repeat hepatectomy was not significantly different between the non-obese group (n
      = 44) and the obese group (n = 16). However, patients in the obese group showed a
      significantly poorer long-term prognosis than those in the non-obese group (P <
      0.05, five-year survival rate; 51.9% and 92.0%, respectively). CONCLUSION:
      Obesity alone may not have an adverse effect on the surgical outcomes of patients
      with primary HCC. However, greater caution seems to be required when planning a
      repeat hepatectomy for obese patients with recurrent HCC.

PMID- 18330948
TI  - Prevalence of anti-HAV antibodies in multitransfused patients with beta
      thalassemia.
AB  - AIM: To detect the prevalence of anti-HAV IgG antibodies in adult multitransfused
      beta-thalassemic patients. METHODS: We studied 182 adult beta-thalassemic
      patients and 209 controls matched for age and sex from the same geographic area,
      at the same time. Anti-HAV IgG antibodies, viral markers of hepatitis B virus
      (HBV) and hepatitis C virus (HCV) infection were evaluated. RESULTS: Anti-HAV IgG
      antibodies were detected more frequently in thalassemic patients (133/182; 73.1%)
      than in healthy controls (38/209; 18.2%, P < 0.0005). When we retrospectively
      evaluated the prevalence of anti-HAV IgG antibodies in 176/182 (96.7%)
      thalassemic patients, whose medical history was available for the previous ten
      years, it was found that 83 (47.2%) of them were continuously anti-HAV IgG
      positive, 16 (9.1%) acquired anti-HAV IgG antibody during the previous ten years,
      49 (27.8%) presented anti-HAV positivity intermittently and 28 (15.9%) were anti
      HAV negative continuously. CONCLUSION: Multitransfused adult beta-thalassemic
      patients present higher frequency of anti-HAV IgG antibodies than normal
      population of the same geographic area. This difference is difficult to explain,
      but it can be attributed to the higher vulnerability of thalassemics to HAV
      infection and to passive transfer of anti-HAV antibodies by blood transfusions.

PMID- 18330949
TI  - Prevalence and determinants of delayed gastric emptying in hospitalised Type 2
      diabetic patients.
AB  - AIM: To determine the prevalence of delayed gastric emptying (GE) in older
      patients with Type 2 diabetes mellitus. METHODS: One hundred and forty seven
      patients with Type 2 diabetes, of whom 140 had been hospitalised, mean age 62.3
      +/- 8.0 years, HbA1c 9.1% +/- 1.9%, treated with either oral hypoglycemic drugs
      or insulin were studied. GE of a solid meal (scintigraphy), autonomic nerve
      function, upper gastrointestinal symptoms, acute and chronic glycemic control
      were evaluated. Gastric emptying results were compared to a control range of
      hospitalised patients who did not have diabetes. RESULTS: Gastric emptying was
      delayed (T50 > 85 min) in 17.7% patients. Mean gastric emptying was slower in
      females (T50 72.1 +/- 72.1 min vs 56.9 +/- 68.1 min, P = 0.02) and in those
      reporting nausea (112.3 +/- 67.3 vs 62.7 +/- 70.0 min, P < 0.01) and early
      satiety (114.0 +/- 135.2 vs 61.1 +/- 62.6 min, P = 0.02). There was no
      correlation between GE with age, body weight, duration of diabetes, neuropathy,
      current glycemia or the total score for upper gastrointestinal symptoms.
      CONCLUSION: Prolonged GE occurs in about 20% of hospitalised elderly patients
      with Type 2 diabetes when compared to hospitalised patients who do not have
      diabetes. Female gender, nausea and early satiety are associated with higher
      probability of delayed GE.

PMID- 18330950
TI  - Mutations in components of the Wnt signaling pathway in gastric cancer.
AB  - AIM: To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of
      Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined
      AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta-catenin) exon3 mutations in 70 GCs.
      METHODS: The presence of mutations was identified by polymerase chain reaction
      (PCR)-based denaturing high-performance liquid chromatography and direct DNA
      sequencing. Beta-catenin expression was detected by immunohistochemical analysis.
      RESULTS: Among the 70 GCs, 5 (7.1%) had mutations in one or two of these three
      components. A frameshift mutation (1 bp deletion) in exon7 of AXIN2 was found in
      one case. Four cases, including the case with a mutation in AXIN2, had frameshift
      mutations and missense mutations in AXIN1. Five single nucleotide polymorphisms
      (SNPs), 334 C>T, 874 C>T, 1396 G>A, 1690 C>T and 1942 T>G, were identified in
      AXIN1. A frameshift mutation (27 bp deletion) spanning exon3 of CTNNB1 was
      observed in one case. All four cases with mutations in AXIN1 and AXIN2 showed
      nuclear beta-catenin expression. CONCLUSION: These data indicate that the
      mutations in AXIN1 and AXIN2 may contribute to gastric carcino-genesis.

PMID- 18330951
TI  - Angiopoietin-1 targeted RNA interference suppresses angiogenesis and tumor growth
      of esophageal cancer.
AB  - AIM: To determine the inhibitory effect of the adenovirus-based angiopoietin-1
      (Ang-1) targeted small interfering RNA expression system (Ad/Ang-1si) on the
      expression of the Ang-1 gene, cell growth and apoptosis in human esophageal
      cancer cell line Eca109. METHODS: siRNA-expressing adenovirus targeting Ang-1
      gene was constructed using the Ad Easy System. Cultured Eca109 cells were
      transfected with Ad/Ang-1si (Eca109/Ang-1si), and Ad/si was used to infect Eca109
      cells as control (Eca109/si). Ang-1 gene expression and concentration was
      determined with RT-PCR and ELISA, respectively. Human umbilical vein endothelial
      cell (HUVEC) migration and proliferation were analyzed. After s.c. injection into
      athymic nu/nu mice, the tumor growth, vessel density and apoptosis of each group
      was also determined. RESULTS: HUVEC migration induced by conditioned medium from
      Ang-1si-transfected Eca109 cells was significantly less than that induced by
      conditioned medium from Eca109 cells and control adenovirus-transfected Eca109
      cells. Furthermore, after s.c. injection into athymic nu/nu mice, the tumor
      growth and cell apoptosis of Ad/Ang-1si -expressing Eca109 cells was
      significantly lower than that of parental or control adenovirus-transfected
      cells. Vessel density assessed by CD31 immunohistochemical analysis and Ang-1
      expression by RT-PCR were also decreased. CONCLUSION: The targeting Ang-1 may
      provide a therapeutic option for esophageal cancer.

PMID- 18330952
TI  - Refined mapping of loss of heterozygosity on 1q31.1-32.1 in sporadic colorectal
      carcinoma.
AB  - AIM: To explore precise deleted regions and screen the candidate tumor suppressor
      genes related to sporadic colorectal carcinoma. METHODS: Six markers on 1q31.1
      32.1 were chosen. These polymorphic microsatellite markers in 83 colorectal
      cancer patients tumor and normal DNA were analyzed via PCR. PCR products were
      electrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1
      software were used for Loss of heterozygosity (LOH) scanning and analysis.
      Comparison between LOH frequency and clinicopathological factors was performed by
      c2 test. RESULTS: 1q31.1-32.1 exhibited higher LOH frequency in colorectal
      carcinoma. The average LOH frequency of 1q31.1-32.1 was 23.0%, with the highest
      frequency of 36.7% (18/49) at D1S2622, and the lowest of 16.4% (11/67) at D1S412,
      respectively. A minimal region of frequent deletion was located within a 2 cM
      genomic segment at D1S413-D1S2622 (1q31.3-32.1). There was no significant
      association between LOH of each marker on 1q31.1-32.1 and the clinicopathological
      data (patient sex, age, tumor size, growth pattern or Dukes stage), which
      indicated that on 1q31.1-32.1, LOH was a common phenomenon in all kinds of
      sporadic colorectal carcinoma. CONCLUSION: Through our refined deletion mapping,
      the critical and precise deleted region was located within 2 cM chromosomal
      segment encompassing 2 loci (D1S413, D1S2622). No significant association was
      found between LOH and clinicopathologic features in 1q31.1-32.1.

PMID- 18330953
TI  - Colorectal carcinoma-associated antigen Ca-Hb3 detected by one-dimensional SDS
      polyacrylamide gel electrophoresis and liquid chromatography-tandem mass
      spectrometry.
AB  - AIM: To comprehensively identify the proteins of tumor relative antigen Ca-Hb3
      recognized by colorectal carcinoma monoclonal antibody Hb3. METHODS: Ca-Hb3 was
      isolated by SDS-polyacrylamide gel electrophoresis (PAGE) followed by digestion
      with trypsin. Trypsin peptides were analyzed by liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). The proteins identified by mass spectrometry were
      analyzed using bioinformatics. RESULTS: Ca-Hb3 was identified as a CKAP4-like
      protein by Nano HPLC tandem mass spectrometry analysis. The molecular weight of
      CKAP4-like protein was 62.02 kDa, including one hydrophobic region, one
      transmembrane domain, five coiled coils, four glycosylation sites and forty-nine
      phosphorylation sites. CKAP4-like protein had a high homogeneity with
      DeltaNp63alpha. The characteristic expression of DeltaNp63alpha that is
      considered a potential oncogene in the isoforms of p63 was similar to that of Ca
      Hb3. CONCLUSION: Ca-Hb3 is probably a CKAP4-like protein, belonging to
      DeltaNp63alpha isoform of p63 family.

PMID- 18330954
TI  - Inhibition of hepatitis B virus replication by pokeweed antiviral protein in
      vitro.
AB  - AIM: To explore the inhibitory effects of pokeweed antiviral protein seed (PAP-S)
      and PAP encoded by a eukaryotic expression plasmid on hepatitis B virus (HBV)
      replication in vitro. METHODS: HepG2 2.2.15 cells in cultured medium were treated
      with different concentrations of PAP-S. HBsAg, HBeAg and HBV DNA in supernatants
      were determined by ELISA and fluorescent quantitative PCR respectively. MTT
      method was used to assay for cytotoxicity. HepG2 were cotransfected with various
      amounts of PAP encoded by a eukaryotic expression plasmid and replication
      competent wild-type HBV 1.3 fold over-length plasmid. On d 3 after transfection,
      HBsAg and HBeAg were determined by using ELISA. Levels of HBV core-associated DNA
      and RNA were detected by using Southern and Northern blot, respectively. RESULTS:
      The inhibitory effects of PAP-S on HBsAg, HBeAg and HBV DNA were gradually
      enhanced with the increase of PAP concentration. When the concentration of PAP-S
      was 10 mug/mL, the inhibition rates of HBsAg, HBeAg and HBV DNA were 20.9%, 30.2%
      and 50%, respectively. After transfection of 1.0 microg and 2.0 microg plasmid
      pXF3H-PAP, the levels of HBV nucleocapside-associated DNA were reduced by 38.0%
      and 74.0% respectively, the levels of HBsAg in the media by 76.8% and 99.7%
      respectively, and the levels of HBeAg by 72.7% and 99.3% respectively as compared
      with controls. Transfection with 2 mug plasmid pXF3H-PAP reduced the levels of
      HBV nucleocapside-associated RNA by 69.0%. CONCLUSION: Both PAP-S and PAP encoded
      by a eukaryotic expression plasmid could effectively inhibit HBV replication and
      antigen expression in vitro, and the inhibitory effects were dose-dependent.

PMID- 18330955
TI  - Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese
      obese children.
AB  - AIM: To investigate the effect of lifestyle intervention on non-alcoholic fatty
      liver disease (NAFLD) in Chinese obese children. METHODS: Seventy-six obese
      children aged from 10 to 17 years with NAFLD were enrolled for a one-month
      intervention and divided randomly into three groups. Group1, consisting of 38
      obese children, was an untreated control group without any intervention. Group 2,
      consisting of 19 obese children in summer camp, was strictly controlled only by
      life style intervention. Group 3, consisting of 19 obese children, received oral
      vitamin E therapy at a dose of 100 mg/d. The height, weight, fasting blood
      glucose (FBG), fasting serum insulin (FINS), plasma alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol
      (TCHO) and homeostasis model assent-insulin resistance (HOMA-IR) were measured at
      baseline and after one month. All patients were underwent to an ultrasonographic
      study of the liver performed by one operator who was blinded to the groups.
      RESULTS: The monitor indices of BMI, ALT, AST, TG, TCHO and HOMA-IR were
      successfully improved except in group 1. BMI and ALT in group 2 were reduced more
      significantly than in group 3 (2.44 +/- 0.82 vs 1.45 +/- 0.80, P = 0.001; 88.58
      +/- 39.99 vs 63.69 +/- 27.05, P = 0.040, respectively). CONCLUSION: Both a short
      term lifestyle intervention and vitamin E therapy have an effect on NAFLD in
      obese children. Compared with vitamin E, lifestyle intervention is more
      effective. Therefore, lifestyle intervention should represent the first step in
      the management of children with NAFLD.

PMID- 18330956
TI  - A pilot study on combination of cryosurgery and (125)iodine seed implantation for
      treatment of locally advanced pancreatic cancer.
AB  - AIM: To study the therapeutic value of combination of cryosurgery and (125)iodine
      seed implantation for locally advanced pancreatic cancer. METHODS: Forty-nine
      patients with locally advanced pancreatic cancer (males 36, females 13), with a
      median age of 59 years, were enrolled in the study. Twelve patients had liver
      metastases. In all cases the tumors were considered unresectable after a
      comprehensive evaluation. Patients were treated with cryosurgery, which was
      performed intraoperatively or percutaneously under guidance of ultrasound and/or
      computed tomography (CT), and (125)iodine seed implantation, which was performed
      during cryosurgery or post-cryosurgery under guidance of ultrasound and/or CT. A
      few patients received regional celiac artery chemotherapy. RESULTS: Thirteen
      patients received intraoperative cryosurgery and 36 received percutaneous
      cryosurgery. Some patients underwent repeat cryosurgery. (125)Iodine seed
      implantation was performed during freezing procedure in 35 patients and 3-9 d
      after cryosurgery in 14 cases. Twenty patients, 10 of whom had hepatic metastases
      received regional chemotherapy. At 3 mo after therapy, CT was repeated to
      estimate tumor response to therapy. Most patients showed varying degrees of tumor
      necrosis. Complete response (CR) of tumor was seen in 20.4% patients, partial
      response (PR), in 38.8%, stable disease (SD), in 30.6%, and progressive disease
      (PD), in 10.2%. Adverse effects associated with cryosurgery included upper
      abdomen pain and increased serum amylase. Acute pancreatitis was seen in 6
      patients one of whom developed severe pancreatitis. All adverse effects were
      controlled by medical management with no poor outcome. There was no therapy
      related mortality. During a median follow-up of 18 mo (range of 5-40), the median
      survival was 16.2 mo, with 26 patients (53.1%) surviving for 12 mo or more.
      Overall, the 6-, 12-, 24- and 36-mo survival rates were 94.9%, 63.1%, 22.8% and
      9.5%, respectively. Eight patients had survival of 24 mo or more. The patient
      with the longest survival (40 mo) is still living without evidence of tumor
      recurrence. CONCLUSION: Cryosurgery, which is far less invasive than conventional
      pancreatic resection, and is associated with a low rate of adverse effects,
      should be the treatment of choice for patients with locally advanced pancreatic
      cancer. (125)Iodine seed implantation can destroy the residual surviving cancer
      cells after cryosurgery. Hence, a combination of both modalities has a
      complementary effect.

PMID- 18330957
TI  - Changes of histology and expression of MMP-2 and nm23-H1 in primary and
      metastatic gastric cancer.
AB  - AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1
      in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven
      gastric cancer patients with lymph node and/or distal metastasis between 1997 and
      2001 were reviewed. Differences in histology of the primary and metastatic
      gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in
      44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and
      moderately differentiated metastatic gastric cancer was found in 88.7% (157/177)
      and primary gastric cancer in 75.7% (134/177) of the patients. The histological
      type of metastatic gastric cancer that was not completely in accordance with the
      preponderant histology of primary gastric cancer was observed in 25 patients
      (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly
      stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity
      showed no difference in primary and metastatic gastric cancer. CONCLUSION:
      Metastatic gastric cancer presents more aggressive histological morphology and
      higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may
      elicit a possible mechanism of gastric cancer metastasis.

PMID- 18330958
TI  - Entecavir up-regulates dendritic cell function in patients with chronic hepatitis
      B.
AB  - AIM: To investigate the in vitro effect of entecavir (ETV) on the function of
      dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients. METHODS:
      Mononuclear cells were isolated from peripheral blood of patients with CHB. DCs
      were incubated with RPMI-1640 medium supplemented with fetal bovine serum, IL-4,
      granulocyte-macrophage colony-stimulating factor (GM-CSF). DCs were treated with
      or without ETV on the fourth day. Cell surface molecules, including CD1a, CD80,
      CD83 and HLA-DR, were assessed by flow cytometry. Concentrations of IL-6 and IL
      12 in the supernatant were assayed by enzyme-linked immunosorbent assay (ELISA).
      The ability of the generated DCs to stimulate lymphocyte proliferation was
      observed. RESULTS: Compared with CHB control group, the expression levels of CD1a
      (29.07 +/- 3.20 vs 26.85 +/- 2.80), CD83 (25.66 +/- 3.19 vs 23.21 +/- 3.10), CD80
      (28.00 +/- 2.76 vs 25.75 +/- 2.51) and HLA-DR (41.96 +/- 3.81 vs 32.20 +/- 3.04)
      in ETV-treated group were higher (P < 0.05). ETV-treated group secreted
      significantly more IL-12 (157.60 +/- 26.85 pg/mL vs 132.60 +/- 22.00 pg/mL (P <
      0.05) and had a lower level of IL-6 in the culture supernatant (83.05 +/- 13.88
      pg/mL vs 93.60 +/- 13.61 pg/mL, P < 0.05) than CHB control group. The ability of
      DCs to stimulate the proliferation of allogeneic lymphocytes was increased in ETV
      treated group compared with CHB control group (1.53 +/- 0.09 vs 1.42 +/- 0.08, P
      < 0.05). CONCLUSION: Entecavir can enhance the biological activity of DCs derived
      from CHB patients.

PMID- 18330959
TI  - Pseudocirrhosis in a pancreatic cancer patient with liver metastases: a case
      report of complete resolution of pseudocirrhosis with an early recognition and
      management.
AB  - We report a case of pseudocirrhosis arising in the setting of regression of liver
      metastases from pancreatic cancer. A 55-year-old asymptomatic woman presented to
      our clinic with newly diagnosed metastatic pancreatic cancer with extensive liver
      metastases. She underwent systemic chemotherapy with gemcitabine and oxaliplatin
      (GEMOX). After 8 cycles of therapy, she had a remarkable response to the therapy
      evidenced by decline of carcinoembryonic antigen (CEA) and CA19 by > 50% and
      nearly complete resolution of hepatic metastases in computed tomography (CT)
      scan. Shortly after, she developed increasing bilateral ankle edema and ascites,
      associated with dyspnea, progressive weight gain, and declining performance
      status. Gemcitabine and oxaliplatin were discontinued as other causes of her
      symptoms such as congestive heart disease or venous thrombosis were ruled out. CT
      scan 6 mo after the initiation of GEMOX revealed worsening ascites with a stable
      pancreatic mass. However, it also revealed a lobular hepatic contour, segmental
      atrophy, and capsular retraction mimicking the appearance of cirrhosis. She was
      managed with aggressive diuresis and albumin infusions which eventually resulted
      in a resolution of the above-mentioned symptoms as well as complete resolution of
      pseudocirrhotic appearance of the liver and ascites in CT scan. This case
      demonstrates that pancreatic cancer patients can develop pseudocirrhosis.
      Clinicians and radiologist should be well aware of this entity as early
      recognition and management can lead to a near complete recovery of liver function
      and much improved quality of life as illustrated in this case.

PMID- 18330960
TI  - A case of asymptomatic intraductal papillary neoplasm of the bile duct without
      hepatolithiasis.
AB  - A 65-year-old woman was found to have dilatation of the intrahepatic bile duct in
      the right anterior segment during a general health. Laboratory data were within
      normal ranges and no solid mass was detected in her abdominal computer tomography
      (CT) or nuclear magnetic resonance imaging (MRI). However, endoscopic retrograde
      cholangiopancreatography (ERCP) demonstrated an obstruction of the right bile
      duct. Intraoperative cholangiography showed stenosis of the intrahepatic bile
      duct in the anterior inferior segment (B5) and narrowness of the intrahepatic
      bile duct in the anterior superior segment (B8), so that we strongly suspected
      intrahepatic cholangiocarcinoma (ICC). Histologically, surgically resected liver
      specimens, without tumor mass by macroscopic observation, showed intraductal
      papillary proliferation with fibrovascular cores and intraductal spreading of
      carcinoma in situ throughout a considerable area, especially in bile ductules
      around the peripheral small portal area. Furthermore, the immunohistochemical
      profile of the tumor (MUC5AC+/CK7+) was compatible with an intraductal papillary
      neoplasm of the bile duct (IPN-B). Consequently, this case was diagnosed as IPN-B
      with spreading CIS, stage I (pT1, pN0, P0, H1, M0). We report a case of IPN-B
      with interesting histopathological findings and emphasize that cholangiography is
      especially helpful for the diagnosis of bile duct dilatation due to infiltration
      of carcinoma cells.

PMID- 18330961
TI  - Protein-loosing enteropathy associated with rotavirus infection in an infant.
AB  - Rotavirus is an acute enteric pathogen in infants and children. We reported a
      rare case of a 6-mo-old infant with protein-loosing enteropathy (PLE) caused by
      rotavirus gastroenteritis, and evaluated the immunological profile in peripheral
      blood lymphocytes. Laboratory examinations showed lymphopenia, hypoproteinemia,
      hypoalbuminemia, hypogammaglobulinemia, and elevation of alpha-1-antitrypsin
      (alpha1-AT) clearance. Lymphocytes subpopulation study revealed the reversal of
      CD4+/CD8+ ratio with the selective decrease of CD4-positive lymphocytes.
      Moreover, the excessive increase of T cells producing IFN-gamma (IFN-gamma) was
      found, which plays an important role in the protection against viral infection.
      The primary or secondary activation of immune system by rotavirus may influence
      structural integrity and vascular permeability, which may play a triggering role
      in protein-loosing enteropathy.

PMID- 18330962
TI  - Melanoma of the rectum: a rare entity.
AB  - A 41-year-old man presented with a 6-mo history of changed defecation and rectal
      bleeding. A 3-cm polypoid tumor of the lower rectum was found at
      rectosigmoidoscopy, which proved to be a leiomyosarcoma upon biopsy.
      Dissemination studies did not show any metastases. He was underwent to an
      abdomino-perineal resection (APR). Histopathology of the specimen showed a
      melanoma (S-100 stain positive). Two years after the resection, metastases in the
      abdomen and right lung were found. He died one and half years later. Primary
      anorectal melanoma is a rare and very aggressive disorder. According to current
      data, one should always perform a S-100 stain when anorectal sarcoma is
      suspected. A positive S-100 stain suggests the tumour to be most likely a
      melanoma. Subsequently, thorough dissemination studies need to be performed.
      Depending on the outcome of the dissemination studies, a surgical resection has
      to be performed. Nowadays, a sphincter-saving local excision combined with
      adjuvant loco-regional radiotherapy should be preferred in case of small tumors.
      The same loco-regional control is achieved with less "loss of function" compared
      to non-sphincter saving surgery. Only in the case of large and obstructing tumors
      an abdomino-perineal resection is the treatment of choice.

PMID- 18330963
TI  - Preface on making oxygen.

PMID- 18330964
TI  - Crystal structure of the oxygen-evolving complex of photosystem II.
AB  - The oxygen in our atmosphere is derived from and maintained by the water
      splitting process of photosynthesis. The enzyme that facilitates this reaction
      and therefore underpins virtually all life on our planet is known as photosystem
      II (PSII). It is a multisubunit enzyme embedded in the lipid environment of the
      thylakoid membranes of plants, algae, and cyanobacteria. Powered by light, PSII
      catalyzes the chemically and thermodynamically demanding reaction of water
      splitting. In so doing, it releases molecular oxygen into the atmosphere and
      provides the reducing equivalents required for the conversion of carbon dioxide
      into the organic molecules of life. Recently, a fully refined structure of an
      isolated 700 kDa cyanobacterial dimeric PSII complex was elucidated by X-ray
      crystallography, which gave organizational and structural details of the 19
      subunits (16 intrinsic and 3 extrinsic) that make up each monomer and provided
      information about the position and protein environments of the many different
      cofactors it binds. The water-splitting site was revealed as a cluster of four Mn
      ions and a Ca ion surrounded by amino acid side chains, of which six or seven
      form direct ligands to the metals. The metal cluster was originally modeled as a
      cubane-like structure composed of three Mn ions and the Ca (2+) linked by oxo
      bonds and the fourth Mn attached to the cubane via one of its O atoms. New data
      from X-ray diffraction and X-ray spectroscopy suggest some alternative
      arrangements. Nevertheless, all of the models are sufficiently similar to provide
      a basis for discussing the chemistry by which PSII splits water and makes oxygen.

PMID- 18330965
TI  - Where water is oxidized to dioxygen: structure of the photosynthetic Mn4Ca
      cluster from X-ray spectroscopy.
AB  - Light-driven oxidation of water to dioxygen in plants, algae, and cyanobacteria
      is catalyzed within photosystem II (PS II) by a Mn 4Ca cluster. Although the
      cluster has been studied by many different methods, its structure and mechanism
      have remained elusive. X-ray absorption and emission spectroscopy and extended X
      ray absorption fine structure studies have been particularly useful in probing
      the electronic and geometric structures and the mechanism of the water oxidation
      reaction. Recent progress, reviewed here, includes polarized X-ray absorption
      spectroscopy measurements of PS II single crystals. Analysis of those results has
      constrained the Mn 4Ca cluster geometry to a set of three similar high-resolution
      structures. The structure of the cluster from the present study is unlike either
      the 3.0- or 3.5-A-resolution X-ray structures or other previously proposed
      models. The differences between the models derived from X-ray spectroscopy and
      crystallography are predominantly because of damage to the Mn 4Ca cluster by X
      rays under conditions used for the structure determination by X-ray
      crystallography. X-ray spectroscopy studies are also used for studying the
      changes in the structure of the Mn 4Ca catalytic center as it cycles through the
      five intermediate states known as the S i states ( i = 0-4). The electronic
      structure of the Mn 4Ca cluster has been studied more recently using resonant
      inelastic X-ray scattering spectroscopy (RIXS), in addition to the earlier X-ray
      absorption and emission spectroscopy methods. These studies are revealing that
      the assignment of formal oxidation states is overly simplistic. A more accurate
      description should consider the charge density on the Mn atoms, which includes
      the covalency of the bonds and delocalization of the charge over the cluster. The
      geometric and electronic structures of the Mn 4Ca cluster in the S states derived
      from X-ray spectroscopy are leading to a detailed understanding of the mechanism
      of O-O bond formation during the photosynthetic water-splitting process.

PMID- 18330966
TI  - Mechanisms of water oxidation from the blue dimer to photosystem II.
AB  - The blue dimer, cis, cis-[(bpy)2(H2O)Ru(III)ORu(III)(H2O)(bpy)2](4+), is the
      first designed, well-defined molecule known to function as a catalyst for water
      oxidation. It meets the stoichiometric requirements for water oxidation, 2H2O -->
      -4e(-), -4H(+) O-O, by utilizing proton-coupled electron-transfer (PCET)
      reactions in which both electrons and protons are transferred. This avoids charge
      buildup, allowing for the accumulation of multiple oxidative equivalents at the
      Ru-O-Ru core. PCET and pathways involving coupled electron-proton transfer (EPT)
      are also used to avoid high-energy intermediates. Application of density
      functional theory calculations to molecular and electronic structure supports the
      proposal of strong electronic coupling across the micro-oxo bridge. The results
      of this analysis provide explanations for important details of the descriptive
      chemistry. Stepwise e(-)/H(+) loss leads to the higher oxidation states
      [(bpy)2(O)Ru(V)ORu(IV)(O)(bpy)2] (3+) (Ru(V)ORu(IV)) and
      [(bpy)2(O)Ru(V)ORu(V)(O)(bpy)2](4+) (Ru(V)ORu(V)). Both oxidize water,
      Ru(V)ORu(IV) stoichiometrically and Ru(V)ORu(V) catalytically. In strongly acidic
      solutions (HNO3, HClO4, and HSO3CF3) with excess Ce(IV), the catalytic mechanism
      involves O---O coupling following oxidation to Ru(V)ORu(V), which does not build
      up as a detectable intermediate. Direct evidence has been found for intervention
      of a peroxidic intermediate. Oxidation of water by Ru(V)ORu(IV) is far slower. It
      plays a role late in the catalytic cycle when Ce(IV) is depleted and is one
      origin of anated intermediates such as [(bpy)2(HO)Ru(IV)ORu(IV)(NO3)(bpy)2](4+),
      which are deleterious in tying up active components in the catalytic cycle. These
      intermediates slowly return to [(bpy)2(H2O)Ru(IV)ORu(III)(OH2)(bpy)2](5+) with
      anion release followed by water oxidation. The results of a recent analysis of
      water oxidation in the oxygen-evolving complex (OEC) of photosystem II reveal
      similarities in the mechanism with the blue dimer and significant differences.
      The OEC resides in the thylakoid membrane in the chloroplasts of green plants,
      and careful attention is paid in the structure to PCET, EPT, and long-range
      proton transfer by sequential local proton transfers. The active site for water
      oxidation is a CaMn 4 cluster, which includes an appended Mn site, Mn(4), where O
      --O coupling is thought to occur. Photochemical electron transfer results in
      oxidation of tyrosine Y Z to Y Z (.), which is approximately 7 A from Mn(4). It
      subsequently oxidizes the OEC through the stepwise stages of the Kok cycle. O---O
      coupling appears to occur through an initial peroxidic intermediate formed by
      redox nucleophilic attack of coordinated OH(-) in Ca-OH(-) on Mn (IV)=O.

PMID- 18330967
TI  - Mechanisms of water oxidation catalyzed by ruthenium diimine complexes.
AB  - (18)O-isotope-labeling studies have led to the conclusion that there exist two
      major pathways for water oxidation catalyzed by dimeric ruthenium ions of the
      general type cis, cis-[L2Ru(III)(OH2)]2O(4+). We have proposed that both pathways
      involve concerted addition of H and OH fragments derived from H 2O to the
      complexes in their four-electron-oxidized states, i.e., [L2Ru(V)(O)]2O(4+),
      ultimately generating bound peroxy intermediates that decay with the evolution of
      O2. The pathways differ primarily in the site of addition of the OH fragment,
      which is either a ruthenyl O atom or a bipyridine ligand. In the former case,
      water addition is thought to give rise to a critical intermediate whose structure
      is L2Ru(IV)(OH)ORu(IV)(OOH)L2(4+); the structures of intermediates involved in
      the other pathway are less well defined but may involve bipyridine OH adducts of
      the type L2Ru(V)(O)ORu(IV)(OH)(L(*)OH)L(4+), which could react further to
      generate unstable dioxetanes or similar endoperoxides. Published experimental and
      theoretical support for these pathways is reviewed within the broader context of
      water oxidation catalysis and related reactions reported for other diruthenium
      and group 8 monomeric diimine-based catalysts. New experiments that are designed
      to probe the issue of bipyridine ligand "noninnocence" in catalysis are
      described. Specifically, the relative contributions of the two pathways have been
      shown to correlate with substituent effects in 4,4'- and 5,5'-substituted
      bipyridine complexes in a manner consistent with the formation of a reactive OH
      adduct intermediate in one of the pathways, and the formation of OH-bipyridine
      adducts during catalytic turnover has been directly confirmed by optical
      spectroscopy. Finally, a photosensitized system for catalyzed water oxidation has
      been developed that allows assessment of the catalytic efficiencies of the
      complex ions under neutral and alkaline conditions; these studies show that the
      ions are far better catalysts than had previously been assumed based upon
      reported catalytic parameters obtained with strong oxidants in acidic media.

PMID- 18330968
TI  - In search of elusive high-valent manganese species that evaluate mechanisms of
      photosynthetic water oxidation.
AB  - Significant progress in the understanding of biological water oxidation has
      occurred during the past 25 years. Today we have a somewhat clearer description
      of the structure of the Mn4Ca cluster and an idea of the appropriate oxidation
      states for the enzyme during catalysis. At issue is the mechanism of water
      oxidation. Depending on one's belief of the manganese ion oxidation levels at the
      catalytically active S4 configuration, one can invoke a variety of different
      processes that could lead to water oxidation. We have suggested that the most
      likely process is the nucleophilic attack of a water bound to calcium (or
      manganese) onto a highly electrophilic Mn(V)=O center. In this Article, we
      explore the difficulties of preparing Mn(V) in dimeric systems and the even more
      arduous task of definitively assigning oxidation states to such highly reactive
      species.

PMID- 18330969
TI  - Theoretical studies of O-O bond formation in photosystem II.
AB  - The most critical part of dioxygen evolution in photosystem II is the O-O bond
      formation step. In order to reach an efficient mechanism, nature uses a unique
      oxygen-evolving complex (OEC) having four manganese and one calcium center. Even
      though the structure of the OEC has become much more clear during recent years,
      it has still been difficult to find a transition state (TS) for O-O bond
      formation with a sufficiently low barrier. However, about a year ago, a quite
      surprising type of TS was found. With the latest X-ray ligand assignment, the
      local barrier for this TS is only 5.1 kcal/mol. It can be described as an attack
      by an oxygen radical, held by a dangling manganese, on a bridging oxo ligand in
      the Mn3Ca cube. In the present short Article, energy diagrams describing the
      entire process of dioxygen formation will be presented. An important conclusion
      drawn from these diagrams is that the major features of dioxygen formation remain
      the same irrespective of which one of the experimentally suggested structures the
      diagram is built on. Compared to earlier presentations of the same type, a
      slightly different approach has been used for setting up the diagrams. Results
      from a recent experimental study of the pressure dependence of oxygen release
      have been used to define the final energy levels. The loss of energy in the
      electron transfer from Tyrz to P680 has also been incorporated into the diagrams.
      A good agreement with experimental observations is demonstrated.

PMID- 18330970
TI  - Water oxidation by a ruthenium complex with noninnocent quinone ligands: possible
      formation of an O-O bond at a low oxidation state of the metal.
AB  - Tanaka and co-workers reported a novel dinuclear Ru complex, [Ru2(OH)2(3,6
      Bu2Q)2(btpyan)](SbF6)2 (3,6-Bu2Q = 3,6-di tert-butyl-1,2-benzoquinone, btpyan =
      1,8-bis(2,2':6',2''-terpyrid-4'-yl)anthracene), that contains redox active
      quinone ligands and has an excellent electrocatalytic activity for water
      oxidation when immobilized on an indium-tin-oxide electrode (Inorg. Chem., 2001,
      40, 329-337). The novel features of the dinuclear and related mononuclear Ru
      species with quinone ligands, and comparison of their properties to those of the
      Ru analogues with the bpy ligand (bpy = 2,2'-bipyridine) replacing quinone, are
      summarized here together with new theoretical and experimental results that show
      striking features for both the dinuclear and mononuclear species. The identity
      and oxidation state of key mononuclear species, including the previously reported
      oxyl radical, have been reassigned. Our gas-phase theoretical calculations
      indicate that the Tanaka Ru-dinuclear catalyst seems to maintain predominantly
      Ru(II) centers while the quinone ligands and water moiety are involved in redox
      reactions throughout the entire catalytic cycle for water oxidation. Our
      theoretical study identifies [Ru2(O2(-))(Q(-1.5))2(btpyan)](0) as a key
      intermediate and the most reduced catalyst species that is formed by removal of
      all four protons before four-electron oxidation takes place. While our study
      toward understanding the complicated electronic and geometric structures of
      possible intermediates in the catalytic cycle is still in progress, the current
      status and new directions for kinetic and mechanistic investigations, and key
      issues and challenges in water oxidation with the Tanaka catalyst (and its
      analogues with Cl(-) or NO(2-)substituted quinones and a species with a xanthene
      bridge instead an antheracene) are discussed.

PMID- 18330971
TI  - Multifrequency pulsed electron paramagnetic resonance study of the S2 state of
      the photosystem II manganese cluster.
AB  - Multifrequency electron spin-echo envelope modulation (ESEEM) spectroscopy is
      employed to measure the strength of the hyperfine coupling of magnetic nuclei to
      the paramagnetic (S = 1/2) S2 form of photosystem II (PSII). Previous X-band
      frequency ESEEM studies indicated that one or more histidine nitrogens are
      electronically coupled to the tetranuclear manganese cluster in the S2 state of
      PSII. However, the spectral resolution was relatively poor at the approximately 9
      GHz excitation frequency, precluding any in-depth analysis of the corresponding
      bonding interaction between the detected histidine and the manganese cluster.
      Here we report ESEEM experiments using higher X-, P-, and Ka-band microwave
      frequencies to target PSII membranes isolated from spinach. The X- to P-band
      ESEEM spectra suffer from the same poor resolution as that observed in previous
      experiments, while the Ka-band spectra show remarkably well-resolved features
      that allow for the direct determination of the nuclear quadrupolar couplings for
      a single I = 1(14)N nucleus. The Ka-band results demonstrate that at an applied
      field of 1.1 T we are much closer to the exact cancellation limit (alpha iso =
      2nu(14)N) that optimizes ESEEM spectra. These results reveal hyperfine (alpha iso
      = 7.3 +/- 0.20 MHz and alpha dip = 0.50 +/- 0.10 MHz) and nuclear quadrupolar
      (e(2)qQ = 1.98 +/- 0.05 MHz and eta = 0.84 +/- 0.06) couplings for a single (14)N
      nucleus magnetically coupled to the manganese cluster in the S 2 state of PSII.
      These values are compared to the histidine imidazole nitrogen hyperfine and
      nuclear quadrupolar couplings found in superoxidized manganese catalase as well
      as (14)N couplings in relevant manganese model complexes.

PMID- 18330972
TI  - Oxygen evolution catalysis by a dimanganese complex and its relation to
      photosynthetic water oxidation.
AB  - [Mn2(III/IV)(mu-O) 2(terpy)2(OH 2)2](NO3)3 (1, where terpy = 2,2':6'2''
      terpyridine) acts as a water-oxidation catalyst with HSO5(-) as the primary
      oxidant in aqueous solution and, thus, provides a model system for the oxygen
      evolving complex of photosystem II (Limburg, J.; et al. J. Am. Chem. Soc. 2001,
      123, 423-430). The majority of the starting [Mn2(III/IV)(mu-O)2](3+) complex is
      converted to the[Mn2(IV/IV)(mu-O)2](4+) form (2) during this reaction (Chen, H.;
      et al. Inorg. Chem. 2007, 46, 34-43). Here, we have used stopped-flow UV-visible
      spectroscopy to monitor UV-visible absorbance changes accompanying the conversion
      of 1 to 2 by HSO5(-). With excess HSO5(-), the rate of absorbance change was
      found to be first-order in [1] and nearly zero-order in [HSO5(-)]. At relatively
      low [HSO5(-)], the change of absorbance with time is distinctly biphasic. The
      observed concentration dependences are interpreted in terms of a model involving
      the two-electron oxidation of 1 by HSO5(-), followed by the rapid reaction of the
      two-electron-oxidized intermediate with another molecule of 1 to give two
      molecules of 2. In order to rationalize biphasic behavior at low [HSO5(-)], we
      propose a difference in reactivity of the [Mn2(III/)(IV)(mu-O)2](3+) complex upon
      binding of HSO5(-) to the Mn(III) site as compared to the reactivity upon binding
      HSO5(-) to the Mn(IV) site. The kinetic distinctness of the Mn(III) and Mn(IV)
      sites allows us to estimate upper limits for the rates of intramolecular electron
      transfer and terminal ligand exchange between these sites. The proposed mechanism
      leads to insights on the optimization of 1 as a water-oxidation catalyst. The
      rates of terminal ligand exchange and electron transfer between oxo-bridged Mn
      atoms in the oxygen-evolving complex of photosystem II are discussed in light of
      these results.

PMID- 18330973
TI  - Ru complexes that can catalytically oxidize water to molecular dioxygen.
AB  - The main objective of this review is to give a general overview of the structure,
      electrochemistry (when available), and catalytic performance of the Ru complexes,
      which are capable of oxidizing water to molecular dioxygen, and to highlight
      their more relevant features. The description of the Ru catalysts is mainly
      divided into complexes that contain a Ru-O-Ru bridging group and those that do
      not. Finally a few conclusions are drawn from the global description of all of
      the catalysts presented here, and some guidelines for future catalyst design are
      given.

PMID- 18330974
TI  - Preparation and study of a family of dinuclear Ru(II) complexes that catalyze the
      decomposition of water.
AB  - An approach is developed for the four-electron oxidation of water to provide
      dioxygen that involves the juxtaposition of two Ru(II) centers such that a metal
      bound water molecule might interact with one or both of the metals. The key
      element in this approach is an appropriate bridging ligand that will hold the
      metal assembly intact through the full redox cycle. Various synthetic approaches
      to such ligands are described with the ultimate preparation of four closely
      related bis-tridentate polypyridine-type systems in which the bridging and distal
      portions of the ligand are varied. All of these ligands self-assemble with two
      Ru(II) centers bridged by a Cl ion in the equatorial plane and four axial
      monodentate substituted pyridines or N-methylimidazoles to form the well
      organized catalyst complexes. These complexes are characterized by their
      distinctive (1)H NMR spectra as well as an X-ray structure of one representative
      species. The photophysical and electrochemical features of these complexes are
      consistent with electronegativity and delocalization effects in the equatorial
      and axial ligands. Of the 14 complexes studied, all but 2, which each contain
      four axial N-methylimidazole ligands, catalyze the decomposition of water in the
      presence of excess Ce(IV) as a sacrificial oxidant at pH = 1. Both the rates of
      oxygen evolution and the catalyst turnover numbers (TNs) are measured. For the
      active catalysts, the relative rates vary from 1 to 51 and the TNs measure from
      80 to 689. Various analytical methods for making these measurements are
      discussed, and it is found that there is an approximately linear relationship
      between the rate and TN. Future work will involve optimization of these systems
      and studies aimed at a better understanding of the mechanism.

PMID- 18330975
TI  - Electronic design criteria for O-O bond formation via metal-oxo complexes.
AB  - Metal-oxos are critical intermediates for the management of oxygen and its
      activation. The reactivity of the metal-oxo is central to the formation of O-O
      bonds, which is the essential step for oxygen generation. Two basic strategies
      for the formation of O-O bonds at metal-oxo active sites are presented. The acid
      base (AB) strategy involves the attack of a nucleophilic oxygen species (e.g.,
      hydroxide) on an electrophilic metal-oxo. Here, active-site designs must
      incorporate the assembly of a hydroxide (or water) proximate to a high-valent
      metal-oxo of even d electron count. For the radical coupling (RC) strategy, two
      high-valent metal-oxos of an odd d electron count are needed to drive O-O
      coupling. This Forum Article focuses on the different electronic structures of
      terminal metal-oxos that support AB and RC strategies and the design of ligand
      scaffolds that engender these electronic structures.

PMID- 18330976
TI  - Chemical stability of the peroxide bond enables diversified synthesis of potent
      tetraoxane antimalarials.
AB  - Of 17 prepared 1,2,4,5-tetraoxacyclohexanes stable to reductive and acidic
      conditions, 3 of them were more active than artemisinin against CQ and MFQ
      resistant strain TM91C235 and all compounds were more active in vitro against W2
      than against D6 strain. In vivo, amines 10 and 11a cured all mice at higher doses
      with MCD < or = 37.5 (mg/kg)/day. Triol 13 was exceptionally active against
      melanoma (LOX IMVI) and ovarian cancer (IGROV1), both with LC 50 = 60 nM.

PMID- 18330977
TI  - Water-soluble pleuromutilin derivative with excellent in vitro and in vivo
      antibacterial activity against gram-positive pathogens.
AB  - Although earlier pleuromutilin analogues showed potent in vitro antibacterial
      activity against some Gram-positive pathogens, their in vivo efficacy was low
      because of insufficient pharmacokinetic properties. We designed novel thioether
      pleuromutilin derivatives having a purine ring as a polar and water solubilizing
      group and identified a promising pleuromutilin analogue 6 with good solubility in
      water ( approximately 50 mg/mL). Compound 6 exhibited excellent in vitro and in
      vivo antibacterial activity against some Gram-positive strains, including drug
      resistant pathogens.

PMID- 18330978
TI  - An updated steroid benchmark set and its application in the discovery of novel
      nanomolar ligands of sex hormone-binding globulin.
AB  - A benchmark data set of steroids with known affinity for sex hormone-binding
      globulin (SHBG) has been widely used to validate popular molecular field-based
      QSAR techniques. We have expanded the data set by adding a number of nonsteroidal
      SHBG ligands identified both from the literature and in our previous experimental
      studies. This updated molecular set has been used herein to develop 4D QSAR
      models based on "inductive" descriptors and to gain insight into the molecular
      basis of protein-ligand interactions. Molecular alignment was generated by means
      of docking active compounds into the active site of the SHBG. Surprisingly, the
      alignment of the benchmark steroids contradicted the classical ligand-based
      alignment utilized in previous CoMFA and CoMSIA models yet afforded models with
      higher statistical significance and predictive power. The resulting QSAR models
      combined with CoMFA and CoMSiA models as well as structure-based virtual
      screening allowed discovering several low-micromolar to nanomolar nonsteroidal
      inhibitors for human SHBG.

PMID- 18330980
TI  - SrAu4In4 and Sr4Au9In13: polar intermetallic structures with cations in augmented
      hexagonal prismatic environments.
AB  - The title compounds were synthesized via high-temperature reactions of the
      elements in welded Ta tubes and characterized by single-crystal X-ray diffraction
      analyses and band structure calculations. SrAu(3.76(2))In(4.24) crystallizes in
      the YCo5In3 structure type with two of eight network sites occupied by mixtures
      of Au and In: Pnma, Z = 4, a = 13.946(7), b = 4.458(2), c = 12.921(6) A. Its
      phase breadth appears to be small. Sr4Au9In 13 exhibits a new structure type, P_6
      m2, Z = 1, a = 12.701(2), c = 4.4350(9) A. The Sr atoms in both compounds center
      hexagonal prisms of nominally alternating In and Au atoms and also have nine
      augmenting (outer) Au + In atoms around their waists so as to define 21-vertex
      Sr@Au9M4In8 (M = Au/In) and Sr@Au9In12 polyhedra, respectively. The relatively
      larger Sr content in the second phase also leads to condensation of some of the
      ideal building units into trefoil-like cages with edge-shared six-member rings.
      One overall driving force for the formation of these structures can be viewed as
      the need for each Sr cation to have as many close neighbors as possible in the
      more anionic Au-In network. The results also depend on the cation size as well as
      on the flexibility of the anionic network and an efficient intercluster
      condensation mode as all clusters are shared. Band structure calculations (LMTO
      ASA) emphasize the greater strengths (overlap populations) of the Au-In bonds and
      confirm expectations that both compounds are metallic.

PMID- 18330979
TI  - Glycosylation site-specific analysis of HIV envelope proteins (JR-FL and CON-S)
      reveals major differences in glycosylation site occupancy, glycoform profiles,
      and antigenic epitopes' accessibility.
AB  - The HIV-1 envelope (Env) is a key determinant in mediating viral entry and fusion
      to host cells and is a major target for HIV vaccine development. While Env is
      typically about 50% glycan by mass, glycosylation sites are known to evolve, with
      some glycosylation profiles presumably being more effective at facilitating
      neutralization escape than others. Thus, characterizing glycosylation patterns of
      Env and native virions and correlating glycosylation profiles with infectivity
      and Env immunogenicity are necessary first steps in designing effective
      immunogens. Herein, we describe a mass spectrometry-based strategy to determine
      HIV-1 Env glycosylation patterns and have compared two mammalian cell expressed
      recombinant Env immunogens, one a limited immunogen and one that induces cross
      clade neutralizing antibodies. We have used a glycopeptide-based mass mapping
      approach to identify and characterize Env's glycosylation patterns by elucidating
      which sites are utilized and what type of glycan motif is present at each
      glycosylation site. Our results show that the immunogens displayed different
      degrees of glycosylation as well as a different characteristic set of glycan
      motifs. Thus, these techniques can be used to (1) define glycosylation profiles
      of recombinant Env proteins and Env on mature virions, (2) define specific
      carbohydrate moieties at each glycosylation site, and (3) determine the role of
      certain carbohydrates in HIV-1 infectivity and in modulation of Env
      immunogenicity.

PMID- 18330981
TI  - Inosylyl(3'-->5')inosine (IpI-). Acid-base and metal ion-binding properties of a
      dinucleoside monophosphate in aqueous solution.
AB  - The acidity constants of the (N7)H(+) sites of inosylyl(3'-->5')inosine (IpI(-))
      were estimated and those of its (N1)H sites were measured by potentiometric pH
      titrations in aqueous solution (25 degrees C; I = 0.1 M, NaNO3). The same method
      was used for the determination of the stability constants of the 1:1 complexes
      formed between Mg(2+), Co(2+), Ni(2+), Zn(2+), or Cd(2+) (= M(2+)) and (IpI -
      H)(2-) and, in the case of Mg(2+), also of (IpI - 2H)(3-). The stability
      constants of the M(IpI)(+) complexes were estimated. The acidity constants of
      H(inosine)(+) and the stability constants of the M(Ino)(2+) and M(Ino - H)(+)
      complexes were taken from the literature. The comparison of these and related
      data allows the conclusion that, in the M(IpI - H) species, chelates are formed;
      most likely they are preferably of an N7/N7 type. For the metal ions Co(2+),
      Ni(2+), Zn(2+), or Cd(2+), the formation degrees of the chelates are on the order
      of 60-80%; no chelates could be detected for the Mg(IpI - H) complexes. It is
      noteworthy that the (N1)H deprotonation, which leads to the M(IpI - H) species,
      occurs in all M(IpI)(+) complexes in the physiological pH range of about 7.5 or
      even below.

PMID- 18330982
TI  - Water-soluble 3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (dmoPTA) as
      a polydentate ligand: synthesis of [RuClCp(PPh3)-mu-dmoPTA-1kappaP:2kappa2N,N'
      Co(acac-kappa2O,O')2].H2O.
AB  - The dinuclear complex [RuClCp(PPh3)-mu-dmoPTA-1kappa P:2kappa(2)N, N'-Co(acac
      kappa(2)O, O') 2].H 2O (2; dmoPTA = 3,7-dimethyl-1,3,7-triaza-5
      phosphabicyclo[3.3.1]nonane) has been synthesized by reaction of
      [RuClCp(HdmoPTA)(PPh3)](OSO2CF3) (1) with Co(acac)2 in methanol (HdmoPTA = 3,7-H
      3,7-dimethyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane). Elemental analysis, IR,
      NMR, and single-crystal X-ray structure determination have characterized the new
      complex. This complex is active for the catalytic isomerization of but-1-en-3-ol
      in acetone better than 1.

PMID- 18330983
TI  - Probing variable amine/amide ligation in Ni(II)N2S2 complexes using sulfur K-edge
      and nickel L-edge X-ray absorption spectroscopies: implications for the active
      site of nickel superoxide dismutase.
AB  - Nickel superoxide dismutase (NiSOD) is a recently discovered metalloenzyme that
      catalyzes the disproportionation of O2(*-) into O2 and H2O2. In its reduced
      state, the mononuclear Ni(II) ion is ligated by two cis-cysteinate sulfurs, an
      amine nitrogen (from the protein N-terminus), and an amide nitrogen (from the
      peptide backbone). Unlike many small molecule and metallopeptide-based NiN2S2
      complexes, S-based oxygenation is not observed in NiSOD. Herein we explore the
      spectroscopic properties of a series of three Ni(II)N2S2 complexes (bisamine
      ligated (bmmp-dmed)Ni(II), amine/amide-ligated (Ni(II)(BEAAM))(-), and bisamide
      ligated (Ni(II)(emi))(2-)) with varying amine/amide ligation to determine the
      origin of the dioxygen stability of NiSOD. Ni L-edge X-ray absorption
      spectroscopy (XAS) demonstrates that there is a progression in ligand-field
      strength with (bmmp-dmed)Ni(II) having the weakest ligand field and
      (Ni(II)(emi))(2-)) having the strongest ligand field. Furthermore, these Ni L
      edge XAS studies also show that all three complexes are highly covalent with
      (Ni(II)(BEEAM))(-) having the highest degree of metal-ligand covalency of the
      three compounds studied. S K-edge XAS also shows a high degree of Ni-S covalency
      in all three complexes. The electronic structures of the three complexes were
      probed using both hybrid-DFT and multiconfigurational SORCI calculations. These
      calculations demonstrate that the nucleophilic Ni(3d)/S(pi)* HOMO of these NiN2S2
      complexes progressively decreases in energy as the amide-nitrogens are replaced
      with amine nitrogens. This decrease in energy of the HOMO deactivates the Ni
      center toward O2 reactivity. Thus, the Ni-S bond is protected from S-based
      oxygenation explaining the enhanced stability of the NiSOD active-site toward
      oxygenation by dioxygen.

PMID- 18330984
TI  - Assembly of the highest connectivity Wells-Dawson polyoxometalate coordination
      polymer: the use of organic ligand flexibility.
AB  - Through tuning the length of flexible bis(triazole) ligands and different metal
      ion coordination geometries, four Wells-Dawson polyoxoanion-based hybrid
      compounds, [Cu 6(btp) 3(P 2W 18O 62)].3H 2O ( 1) (btp = 1,3-bis(1,2,4-triazol-1
      y1)propane), [Cu 6(btb) 3((P 2W 18O 62)].2H 2O ( 2), [Cu 3(btb) 6(P 2W 18O
      62)].6H 2O (btb = 1,4-bis(1,2,4-triazol-1-y1)butane) ( 3), and [Cu 3(btx) 5.5((P
      2W 18O 62)].4H 2O (btx = 1,6-bis(1,2,4-triazol-1-y1)hexane) ( 4), were
      synthesized and structurally characterized. In compound 1, the metal-organic
      motif exhibits a ladder-like chain, which is further fused by the ennead-dentate
      [P 2W 18O 62] (6-) anions to construct a 3D structure. In compound 2, the metal
      organic motif exhibits an interesting Cu-btb grid layer, and the ennead-dentate
      polyoxoanions are sandwiched by two Cu-btb layers to construct a 3D structure.
      Compound 3 exhibits a (4 (2).6 (2).8 (2)) 3D Cu-btb framework with square and
      hexagonal channels arranged alternately. The hexa-dentate polyoxoanions
      incorporate only into the hexagonal channels. In compound 4, there exist two sets
      of (6 (1).10 (2)) 2(6 (1).8 (2).10 (3)) 3D Cu-btx frameworks to generate a 2-fold
      interpenetrated structure into which the penta-dentate polyoxoanions are inserted
      to construct a 3D structure. The structural analyses reveal that the length of
      flexible bis(triazole) ligands and metal ion coordination geometries have a
      synergic influence on the structures of this series. To our knowledge, they have
      the highest connectivity for the Wells-Dawson polyoxometalate coordination
      polymers to date.

PMID- 18330985
TI  - A [4Fe-4S] cluster dimer bridged by bis(2,2':6',2''-terpyridine-4'
      thiolato)iron(II).
AB  - The use of 2,2':6',2''-terpyridine-4'-thiol (tpySH) was explored as a bridging
      ligand for the formation of stable assemblies containing both [4Fe-4S] clusters
      and single metal ions. Reaction of tpySH (2 equiv) with (NH4)2Fe(SO4)(2).6H2O
      generated the homoleptic complex [Fe(tpySH)2](2+), which was isolated as its PF6(
      ) salt. The compound could be fully deprotonated to yield neutral [Fe(tpyS)2],
      and the absorption spectrum is highly dependent on the protonation state.
      Reaction of [Fe(tpySH)2](PF6)2 with the new 3:1 site-differentiated cluster (n
      Bu4N)2[Fe4S4(TriS)(SEt)] yielded the first metal-bridged [4Fe-4S] cluster dimer,
      (n-Bu4N)2[{Fe4S4(TriS)(mu-Stpy)}2Fe]. Electrochemical studies indicate that the
      [4Fe-4S] clusters in the dimer act as independent redox units, while UV-vis
      spectroscopy provides strong evidence for a thioquinonoid electron distribution
      in the bridging tpyS(-) ligand. TpySH thus acts as a directional bridging ligand
      between [4Fe-4S] clusters and single metal ions, thereby opening the way to the
      synthesis of larger, more complex assemblies.

PMID- 18330986
TI  - A coumarin-derived fluorescence probe selective for magnesium.
AB  - Two different coumarin derivatives have been connected via an imine linkage to
      obtain a new fluorescence signaling system. This compound itself does not show
      any emission due to rapid isomerization around the C[double bond]N bond. However,
      in the presence of a Mg(II) ion, this isomerization is stopped because of bonding
      to the metal ion resulting in high-intensity (approximately 550-fold) emission.
      Other metal ions like Li(I), Ca(II), and Zn(II) show very little emission, while
      biologically relevant transition-metal ions do not show any emission. In this
      way, the Mg(II) ion can be detected in the presence of these ions.

PMID- 18330987
TI  - Zinc, cadmium, and mercury 1,2-benzenedithiolates with intramolecular NH...S
      hydrogen bonds.
AB  - Mononuclear Zn, Cd, and Hg 1,2-benzenedithiolates with intramolecular NH...S
      hydrogen bonds, [M(II){1,2-S2-3,6-(RCONH)2C6H2}2](2-) (R = CH 3, t-Bu; M = Zn,
      Cd, Hg), were synthesized and characterized by X-ray analysis and spectral
      measurements. The presence of intramolecular NH...S hydrogen bonds was
      established by the IR spectra. (199)Hg and (113)Cd nuclear magnetic resonance
      showed a stabilized four-thiolate coordinated structure and suggested the
      influence of the NH...S hydrogen bonds to ppi(Hg)-ppi(S) interactions. The NH
      stretching bands show that the NH...S hydrogen bonds in Cd and Hg complexes are
      stronger than those in the corresponding Zn complex. These results are supported
      by theoretical calculations. The experimental and theoretical results suggested
      that the NH...S hydrogen bond influences the efficient capture of toxic Cd and Hg
      ions by metallothioneins.

PMID- 18330989
TI  - In vivo and in vitro production options for fungal secondary metabolites.
AB  - Microbial natural products, among them a vast diversity of fungal origin,
      represent a major source for new drug candidates. Focusing on fungal metabolites,
      our review covers recent advances in the field of biotransformation, heterologous
      expression, in vivo production approaches, genomics, and the metabolism of
      unexplored fungal groups as options to generate and identify new compounds or
      optimize known ones.

PMID- 18330990
TI  - Wheat germ agglutinin functionalized complexation hydrogels for oral insulin
      delivery.
AB  - Insulin was loaded into hydrogel microparticles after two hours with loading
      efficiencies greater than 70% for both poly(methacrylic acid-grafted-ethylene
      glycol) (P(MAA-g-EG)) and poly(methacrylic acid-grafted-ethylene glycol)
      functionalized with wheat germ agglutinin (P(MAA-g-EG) WGA). The pH-responsive
      release results demonstrated that the pH shift from the stomach to the small
      intestine can be used as a physiologic trigger to release insulin from P(MAA-g
      EG) and P(MAA-g-EG) WGA microparticles, thus limiting release of insulin into the
      acidic environment of the stomach. Microplates were successfully treated with PGM
      to create a surface that allowed for specific binding between mucins and lectins.
      The 1% PGM treatment followed by a 2 h BSA blocking step gave the most consistent
      results when incubated with F-WGA. In addition, the PGM-treated microplates were
      shown to create specific interactions between F-WGA and the PGM by use of a
      competitive carbohydrate. The 1% PGM treated microplates were also used to show
      that adhesion was improved in the P(MAA-g-EG) WGA microparticles over the P(MAA-g
      EG) microparticles. The interaction between the PGM-treated microplate and P(MAA
      g-EG) WGA was again shown to be specific by adding a competitive carbohydrate,
      while the interaction between P(MAA-g-EG) and the PGM-treated microplate was
      nonspecific. Cellular monolayers were used as another method for demonstrating
      that the functionalized microparticles increase adhesion over the
      nonfunctionalized microparticles. This work has focused on improving the
      mucoadhesive nature of P(MAA-g-EG) by functionalizing these hydrogel carriers
      with wheat germ agglutinin (WGA) to create a specific mucosal interaction and
      then evaluating the potential of these carriers as oral insulin delivery systems
      by in vitro methods. From these studies, it is concluded that the addition of the
      WGA on the microparticles produces a specific adhesion to carbohydrate-containing
      surfaces and that P(MAA-g-EG) WGA shows great promise as an oral insulin delivery
      system.

PMID- 18330991
TI  - The effect of chitosan on the in vitro biological performance of chitosan
      poly(butylene succinate) blends.
AB  - Chitosan blends with synthetic biodegradable polymers have been proposed for
      various biomedical applications due to their versatile mechanical properties and
      easier processing. However, details regarding the main surface characteristics
      that may benefit from the blending of these two types of materials are still
      missing. Hence, this work aims at investigating the surface properties of
      chitosan-based blends, illustrating the way these properties determine the
      material-proteins interactions and ultimately the behavior of osteoblast-like
      cells. The surface characteristics of modified and nonmodified blends were
      assessed using complimentary techniques such as optical microscopy, scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR-ATR), X
      ray photoelectron spectroscopy (XPS), contact angle measurements and surface
      energy calculations. The adsorption of human serum albumin (HSA) and human plasma
      fibronectin (HFN) onto the different surfaces was quantified by association of an
      indirect method with a colorimetric assay. It was found that the presence of
      chitosan on the surface promoted the adsorption of proteins. Moreover, a
      preferential adsorption of albumin over fibronectin was registered. The in vitro
      biological performance of the studied materials was further investigated by a
      direct contact assay with an osteoblastic-like cell line (SaOs-2). A synergistic
      effect of the two components of the blend was observed. While the synthetic
      polyester promoted the adhesion of SaOs-2, the presence of chitosan significantly
      enhanced the osteoblastic activity of these cells. This work further confirmed
      the interest in designing polymeric blends with natural polymers as a successful
      strategy to enhance the biological performance of a biomaterial.

PMID- 18330992
TI  - Pectin-lipid assembly at the air-water interface: effect of the pectin charge
      distribution.
AB  - Pectins are anionic polysaccharides that are sensitive to cations, a property
      that is widely used in food science. The interactions of a cationic lipid film
      (dimethyldioctadecylammonium bromide, DODAB) with a set of pectins bearing the
      same charge, which was either distributed randomly or pseudorandomly or
      blockwise, are investigated. The combination of Brewster angle microscopy BAM and
      infrared reflection-absorption spectroscopy IRRAS at the air-water interface
      reveals that pectin strongly binds to the cationic lipid film in forming a
      stacked layer underneath the lipid film. The detailed vibrational study of this
      stable mixed film indicates furthermore that pectin induces a disorder in the
      internal structure of the cationic film. The strong binding induces a splitting
      of the carboxylate stretching mode of pectin that is pressure and charge
      distribution dependent. The occurrence of an intermediate plateau below the
      collapse of the mixed film originates probably from a change in conformation of
      the pectin structure underneath the film.

PMID- 18330993
TI  - The berkeleyamides, amides from the acid lake fungus Penicillum rubrum.
AB  - We previously reported several novel bioactive hybrid polyketide-terpenoid
      metabolites from a deep water Penicillium rubrum isolated from Berkeley Pit Lake,
      Butte, Montana. In this paper we report the structures of four new amides,
      berkeleyamides A-D (1, 4, 5, 7), isolated from extracts of this fungus. The
      structures of these compounds were deduced by analysis of NMR data, chemical
      derivatization, and comparison of their spectroscopic data to those of known
      compounds.

PMID- 18330994
TI  - Chaperone-aided in vitro renaturation of an engineered E1 envelope protein for
      detection of anti-Rubella virus IgG antibodies.
AB  - The envelope glycoproteins of Rubella virus, E1 and E2, mediate cell tropism, and
      E1 in particular plays a pivotal role in the fusion of the virus with the
      endosomal membrane. Both are the prime targets of the humoral immune response.
      Recombinant variants of the E1 ectodomain as well as E1 antigen preparations from
      virus lysates are commonly used to detect anti-Rubella immunoglobulins in human
      sera. Hitherto, recombinant E1 for diagnostic applications has been produced
      chiefly in eukaryotic expression systems. Here, we report the high-yield
      overproduction of an engineered E1 ectodomain in the Escherichia coli cytosol and
      its simple and convenient renaturation into a highly soluble and immunoreactive
      conformation. C-Terminal fusion to one or two units of the E. coli chaperone SlyD
      enhances expression, facilitates in vitro refolding, and improves the overall
      solubility of Rubella E1. As part of this fusion protein, the E1 ectodomain
      fragment of residues 201-432 adopts an immunoreactive fold, providing a promising
      tool for the sensitive and specific detection of anti-E1 IgG in Rubella serology.
      Two disulfide bonds in the membrane-adjacent part of the E1 ectodomain are
      sufficient to generate conformations with a high and specific antigenicity. The
      covalently attached chaperone modules do not impair antibody recognition and
      binding of Rubella E1 when assessed in a heterogeneous immunoassay. SlyD and
      related folding helpers are apparently generic tools for the expression and
      refolding of otherwise unavailable proteins of diagnostic or medical importance.

PMID- 18330995
TI  - Thermodynamic characterization of the complete set of sequence symmetric tandem
      mismatches in RNA and an improved model for predicting the free energy
      contribution of sequence asymmetric tandem mismatches.
AB  - Because of the availability of an abundance of RNA sequence information, the
      ability to rapidly and accurately predict the secondary structure of RNA from
      sequence is becoming increasingly important. A common method for predicting RNA
      secondary structure from sequence is free energy minimization. Therefore,
      accurate free energy contributions for every RNA secondary structure motif are
      necessary for accurate secondary structure predictions. Tandem mismatches are
      prevalent in naturally occurring sequences and are biologically important. A
      common method for predicting the stability of a sequence asymmetric tandem
      mismatch relies on the stabilities of the two corresponding sequence symmetric
      tandem mismatches [Mathews, D. H., Sabina, J., Zuker, M., and Turner, D. H.
      (1999) J. Mol. Biol. 288, 911-940]. To improve the prediction of sequence
      asymmetric tandem mismatches, the experimental thermodynamic parameters for the
      22 previously unmeasured sequence symmetric tandem mismatches are reported. These
      new data, however, do not improve prediction of the free energy contributions of
      sequence asymmetric tandem mismatches. Therefore, a new model, independent of
      sequence symmetric tandem mismatch free energies, is proposed. This model
      consists of two penalties to account for destabilizing tandem mismatches, two
      bonuses to account for stabilizing tandem mismatches, and two penalties to
      account for A-U and G-U adjacent base pairs. This model improves the prediction
      of asymmetric tandem mismatch free energy contributions and is likely to improve
      the prediction of RNA secondary structure from sequence.

PMID- 18330996
TI  - Orthogonal cross-seeding: an approach to explore protein aggregates in living
      cells.
AB  - Protein aggregation is associated with the pathology of many diseases, especially
      neurodegenerative diseases. A variety of structurally polymorphic aggregates or
      preaggregates including amyloid fibrils is accessible to any aggregating protein.
      Preaggregates are now believed to be the toxic culprits in pathologies rather
      than mature aggregates. Although clearly valuable, understanding the mechanism of
      formation and the structural characteristics of these prefibrillar species is
      currently lacking. We report here a simple new approach to map the nature of the
      aggregate core of transient aggregated species directly in the cell. The method
      is conceptually based on the highly discriminating ability of aggregates to
      recruit new monomeric species with equivalent molecular structure. Different
      soluble segments comprising parts of an amyloidogenic protein were transiently
      pulse-expressed in a tightly controlled, time-dependent manner along with the
      parent aggregating full-length protein, and their recruitment into the insoluble
      aggregate was monitored immunochemically. We used this approach to determine the
      nature of the aggregate core of the metastable aggregate species formed during
      the course of aggregation of a chimera containing a long polyglutamine repeat
      tract in a bacterial host. Strikingly, we found that different segments of the
      full-length protein dominated the aggregate core at different times during the
      course of aggregation. In its simplicity, the approach is also potentially
      amenable to screen also for compounds that can reshape the aggregate core and
      induce the formation of alternative nonamyloidogenic species.

PMID- 18330997
TI  - Catalytically requisite conformational dynamics in the mRNA-capping enzyme probed
      by targeted molecular dynamics.
AB  - The addition of a N7-methyl guanosine cap to the 5' end of nascent mRNA is
      carried out by the mRNA-capping enzyme, a two-domain protein that is a member of
      the nucleotidyltransferase superfamily. The mRNA-capping enzyme is composed of a
      catalytic nucleotidyltransferase domain and a noncatalytic
      oligonucleotide/oligosaccharide binding (OB) domain. Large-scale domain motion
      triggered by substrate binding mediates catalytically requisite conformational
      rearrangement of the GTP substrate prior to the chemical step. In this study, we
      employ targeted molecular dynamics (TMD) on the PBCV-1 capping enzyme to probe
      the global domain dynamics and internal dynamics of conserved residues during the
      conformational transformation from the open to the closed state. Analysis of the
      resulting trajectories along with structural and sequence homology to other
      members of the superfamily allows us to suggest a conserved mechanism of
      conformational rearrangements spanning all mRNA-capping enzymes and all ATP
      dependent DNA ligases. Our results suggest that the OB domain moves quasi
      statically toward the nucleotidyltransferase domain, pivoting about a short
      linker region. The approach of the OB domain brings a conserved RxDK sequence, an
      element of conserved motif VI, within proximity of the triphosphate of GTP,
      destabilizing the unreactive conformation and thereby allowing thermal
      fluctuations to partition the substrate toward the catalytically competent state.

PMID- 18330998
TI  - Activation of bacterial ribonuclease P by macrolides.
AB  - The effect of macrolide antibiotic spiramycin on RNase P holoenzyme and M1 RNA
      from Escherichia coli was investigated. Ribonuclease P (RNase P) is a ribozyme
      that is responsible for the maturation of 5' termini of tRNA molecules.
      Spiramycin revealed a dose-dependent activation on pre-tRNA cleavage by E. coli
      RNase P holoenzyme and M1 RNA. The K s and V max, as well as the K s(app) and V
      max(app) values of RNase P holoenzyme and M1 RNA in the presence or absence of
      spiramycin, were calculated from primary and secondary kinetic plots. It was
      found that the activity status of RNase P holoenzyme and M1 RNA is improved by
      the presence of spiramycin 18- and 12-fold, respectively. Primer extension
      analysis revealed that spiramycin induces a conformational change of the P10/11
      structural element of M1 RNA, which is involved in substrate recognition.

PMID- 18330999
TI  - Single-electron counting spectroscopy: simulation study of porphyrin in a
      molecular junction.
AB  - Electron counting of a single porphyrin molecule between two electrodes shows a
      crossover from sub- to super-Poissonian statistics as the bias voltage is
      scanned. This is attributed to the simultaneous activation of states with
      electron transfer rates spanning several orders of magnitude. Time-series
      analysis of consecutive single-electron transfer events reveals fast and slow
      transport channels, which are not resolved by the average current alone.

PMID- 18331000
TI  - Immobilizing a drop of water: fabricating highly hydrophobic surfaces that pin
      water droplets.
AB  - We describe the fabrication of a patterned, hydrophobic silicon substrate that
      can pin a water droplet despite its large contact angle. Arrays of nm tips in
      silicon were fabricated by reactive ion etching using polymer masks defined by
      photolithography. A droplet sitting on one class of these substrates did not fall
      even after the substrate was turned upside-down. The production allows the
      fabrication of large arrays of tips with a one-step simple etching process, along
      with silanization, to achieve a substrate with both very large contact and
      tilting angles.

PMID- 18331001
TI  - Spin-polarizable excitonic luminescence in colloidal Mn2+-doped CdSe quantum
      dots.
AB  - The photoluminescence of colloidal Mn2+-doped CdSe nanocrystals has been studied
      as a function of nanocrystal diameter. These nanocrystals are shown to be unique
      among colloidal doped semiconductor nanocrystals reported to date in that quantum
      confinement allows tuning of the CdSe bandgap energy across the Mn2+ excited
      state energies. At small diameters, the nanocrystal photoluminescence is
      dominated by Mn 2+ emission. At large diameters, CdSe excitonic photoluminescence
      dominates. The latter scenario has allowed spin-polarized excitonic
      photoluminescence to be observed in colloidal doped semiconductor nanocrystals
      for the first time.

PMID- 18331002
TI  - Isolation of discrete nanoparticle-DNA conjugates for plasmonic applications.
AB  - Discrete DNA-gold nanoparticle conjugates with DNA lengths as short as 15 bases
      for both 5 and 20 nm gold particles have been purified by anion-exchange HPLC.
      Conjugates comprising short DNA (<40 bases) and large gold particles (> or =20
      nm) are difficult to purify by other means and are potential substrates for
      plasmon coupling experiments. Conjugate purity is demonstrated by hybridizing
      complementary conjugates to form discrete structures, which are visualized by
      TEM.

PMID- 18331003
TI  - Parallel electrophoretic depletion, fractionation, concentration, and desalting
      of 96 complex biological samples for mass spectrometry.
AB  - The preparation of complex biological samples for high-throughput mass
      spectrometric analyses remains a significant bottleneck, limiting advancement of
      the capabilities of mass spectrometry (MS) and ultimately limiting development of
      novel clinical assays. The removal of interfering species (e.g., salts,
      detergents, and buffers), concentration of dilute analytes, and the reduction of
      sample complexity are required in order to maximize the quality of resultant MS
      data. This study describes a novel sample preparation method that makes use of
      electrophoresis to prepare complex biological samples for high-throughput MS
      analysis. The method provides for integration of key sample preparation steps,
      including depletion, fractionation, desalting, and concentration. The prepared
      samples are captured onto a monolithic reversed-phase capture target that can be
      analyzed directly by a mass spectrometer. Up to 96 individual samples are
      simultaneously prepared for MS analysis in under 1 h. For standard proteins added
      to serum, this method provides femtomole level sensitivity and reproducible label
      free detection (coefficient of variation <30%). This study demonstrates that this
      electrophoretic sample preparation system permits high-throughput sample
      preparation for mass spectrometric analysis of complex biological samples, such
      as serum, plasma, and tissue extracts.

PMID- 18331004
TI  - Easy ambient sonic-spray ionization mass spectrometry combined with thin-layer
      chromatography.
AB  - On-spot detection and analyte characterization on thin-layer chromatography (TLC)
      plates is performed via ambient desorption/ionization and (tandem) mass
      spectrometry detection, that is, via easy ambient sonic spray ionization mass
      spectrometry (EASI-MS). As proof-of-principle cases, mixtures of semipolar
      nitrogenated compounds as well as pharmaceutical drugs and vegetable oils have
      been tested. The technique has also been applied to monitor a chemical reaction
      of synthetic importance. EASI is the simplest and gentlest ambient ionization
      technique currently available, assisted solely by N2 (or air). It uses no
      voltages, no electrical discharges; no UV or laser beams, and no high temperature
      and is most easily implemented in all API mass spectrometers. TLC is also the
      simplest, fastest, and most easily performed chromatographic technique. TLC plus
      EASI-MS therefore provide a simple and advantageous combination of
      chromatographic separation and sensitive detection of the TLC spots as well as on
      spot MS or MS/MS characterization. The favorable characteristics of TLC-EASI-MS
      indicate advantageous applications in several areas such as drug and oil
      analysis, phytochemistry and synthetic chemistry, forensics via reliable
      counterfeit detection, and quality control.

PMID- 18331005
TI  - Effects of ionic liquid [bmim][PF6] on absorption spectra and reaction kinetics
      of the duroquinone triplet state in acetonitrile.
AB  - The transient absorption spectra and photoinduced electron-transfer process of
      duroquinone (DQ) in mixed binary solutions of ionic liquid (IL) [bmim][PF6] and
      acetonitrile (MeCN) have been investigated by laser photolysis at an excitation
      wavelength of 355 nm. A spectral blue shift of 3DQ* was observed in the IL/MeCN
      mixtures compared to MeCN. At lower VIL(volume fraction of IL), the interaction
      between DQ and the solvent is dominant, and the decay rate constant (kobs) of
      3DQ* increases steadily with the increasing of VIL; to the contrary, at higher
      VIL, the network structures due to the hydrogen bond and viscosity are dominant,
      and the decay rate constant decreases obviously with increasing VIL. A critical
      point (turnover) was observed at VIL = approximately 0.30. The dependence of the
      observed growth rate (kgr) of the photoinduced electron-transfer (PET) products
      on VIL is complex and shows a special change; kgr first decreases with increasing
      VIL, then increases, and finally decreases slowly with further increasing of VIL.
      It is speculated that the PET process in the mixture can be affected by factors
      including the local structure and the reorganization energy of the solvent and
      salt and cage effects. The change of local structure of [bmim][PF6]/MeCN is
      supported by following the steady-state fluorescence behavior of the mixture, in
      combination with the molecular dynamics simulation of the thermodynamic property.
      The results revealed that the degree of self-aggregation of monomeric cations
      (bmim+) to associated forms increases with increasing VIL. This is in good
      agreement with the laser photolysis results for the same solutions.

PMID- 18331006
TI  - Ultrafast intramolecular charge transfer with strongly twisted
      aminobenzonitriles: 4-(di-tert-butylamino)benzonitrile and 3-(di-tert
      butylamino)benzonitrile.
AB  - The newly synthesized aminobenzonitriles with two bulky amino substituents 4-(di
      tert-butylamino)benzonitrile (DTABN) and 3-(di-tert-butylamino)benzonitrile
      (mDTABN) have strongly twisted amino groups in the ground state. From X-ray
      crystal analysis it is found that the amino twist angle theta of mDTABN equals
      86.5 degrees , whereas a twist angle of around 75 degrees is deduced for DTABN
      from the extinction coefficient of its lowest-energy absorption band in n-hexane.
      Because of the electronic decoupling between the amino and benzonitrile groups
      caused by these large twist angles, the absorption of DTABN and mDTABN is
      relatively weak below 40000 cm-1, with extinction coefficients around 25 times
      smaller than those of the planar 4-(dimethylamino)benzonitrile (DMABN). DTABN as
      well as mDTABN undergo efficient intramolecular charge transfer (ICT) in the
      singlet excited state, in nonpolar (n-hexane) as well as in polar (acetonitrile)
      solvents. Their fluorescence spectra consist of an ICT emission band, without
      evidence for locally excited (LE) fluorescence. The occurrence of efficient ICT
      with mDTABN is different from the findings with all other N,N
      dialkylaminobenzonitriles in the literature, for which ICT only appears with the
      para-derivative. From solvatochromic measurements, an ICT dipole moment of 17 D
      is determined for DTABN as well as for mDTABN, similar to that of DMABN. The
      picosecond fluorescence decays of DTABN (time resolution 3 ps) are effectively
      single exponential. Their decay time is equal to the ICT lifetime tau'0(ICT),
      which increases with solvent polarity from 0.86 ns in n-hexane to 3.48 ns in MeCN
      at 25 degrees C. The femtosecond excited-state absorption (ESA) spectra of DTABN
      in n-hexane and MeCN at 22 degrees C show a decay of the LE and a corresponding
      rise of the ICT absorption. The ICT reaction time is 70 fs in n-hexane and 60 fs
      in MeCN. DTABN and mDTABN may have a strongly twisted ICT state, similar to that
      of 6-cyanobenzoquinuclidine but different from that of DMABN.

PMID- 18331007
TI  - A new scale of electronegativity based on electrophilicity index.
AB  - By calculating the energies of neutral and different ionic forms (M2+, M+, M, M-,
      and M2-) of 32 elements (using B3LYP/6-311++G** level of theory) and taking
      energy (E) to be a Morse-like function of the number of electrons (N), the
      electrophilicity values (omega) are calculated for these atoms. The obtained
      electrophilicities show a good linearity with some commonly used
      electronegativity scales such as Pauling and Allred-Rochow. Using these
      electrophilicities, the ionicities of some diatomic molecules are calculated,
      which are in good agreement with the experimental data. Therefore, these
      electrophilicities are introduced as a new scale for atomic electronegativity,
      chi(omega)0. The same procedure is also performed for some simple polyatomic
      molecules. It is shown that the new scale successfully obeys Sanderson's
      electronegativity equalization principle and for those molecules which have the
      same number of atoms, the ratio of the change in electronegativity during the
      formation of a molecule from its elements to the molecular electronegativity
      (Delta chi/chi omega) is the same.

PMID- 18331008
TI  - Temperature dependences for the reactions of O- and O2- with O2(a1Deltag) from
      200 to 700 K.
AB  - Rate constants and product ion distributions for the O- and O2- reactions with
      O2(a 1Deltag) were measured as a function of temperature from 200 to 700 K. The
      measurements were made in a selected ion flow tube (SIFT) using a newly
      calibrated O2(a 1Deltag) emission detection scheme with a chemical singlet oxygen
      generator. The rate constant for the O2- reaction is approximately 7 x 10(-10)
      cm3 s-1 at all temperatures, approaching the Langevin collision rate constant.
      Electron detachment was the only product observed with O2-. The O- reaction shows
      a positive temperature dependence in the rate constant from 200 to 700 K. The
      product branching ratios show that almost all of the products at 200 K are
      electron detachment, with an increasing contribution from the slightly
      endothermic charge-transfer channel up to 700 K, accounting for 75% of the
      products at that temperature. The increase in the overall rate constant can be
      attributed to this increase in the contribution the endothermic channel. The
      charge-transfer product channel rate constant follows the Arrhenius form, and the
      detachment product channel rate constant is essentially independent of
      temperature with a value of approximately 6.1 x 10(-11) cm3 s-1.

PMID- 18331009
TI  - Experimental and molecular dynamics simulation study of the sublimation and
      vaporization energetics of iron metalocenes. crystal structures of Fe(eta5
      C5H4CH3)2 and Fe[(eta5-(C5H5)(eta5-C5H4CHO)].
AB  - The standard molar enthalpies of sublimation of ferrocene, 1,1'
      dimethylferrocene, decamethylferrocene, ferrocenecarboxaldehyde and alpha
      methylferrocenemethanol, and the enthalpy of vaporization of N,N
      dimethyl(aminomethyl)ferrocene, at 298.15 K, were determined by Calvet-drop
      microcalorimetry and/or the Knudsen effusion method. The obtained values were
      used to assess and refine our previously developed force field for metallocenes.
      The modified force field was able to reproduce the deltasubHdegreesm and
      deltavapHdegreesm values of the test-set with an accuracy better than 5 kJ.mol-1,
      except for decamethylferrocene, in which case the deviation between the
      calculated and experimental deltasubHdegreesm values was 16.1 kJ.mol-1. The
      origin of the larger error found in the prediction of the sublimation energetics
      of decamethylferrocene, and which was also observed in the estimation of
      structural properties (e.g., density and unit cell dimensions), is discussed.
      Finally, the crystal structures of Fe(eta5-C5H4CH3)2 and Fe[(eta5-(C5H5)(eta5
      C5H4CHO)] at 293 and 150 K, respectively, are reported.

PMID- 18331010
TI  - Electronic state spectroscopy of c-C5F8 explored by photoabsorption, electron
      impact, photoelectron spectroscopies and ab initio calculations.
AB  - The electronic transitions and resonance-enhanced vibrational excitations of
      octafluorocyclopentene (c-C5F8) have been investigated using high-resolution
      photoabsorption spectroscopy in the energy range 6-11 eV. In addition, the high
      resolution electron energy loss spectrum (HREELS) was recorded under the electric
      dipolar excitation conditions (100 eV incident energy, approximately 0 degrees
      scattering angle) over the 5-14 eV energy loss range. A He(I) photoelectron
      spectrum (PES) has also been recorded between 11 and 20 eV, allowing us to derive
      a more precise value of (11.288 +/- 0.002) eV for the ground neutral state
      adiabatic ionization energy. All spectra presented in this paper represent the
      first and highest resolution data yet reported for octafluorocyclopentene. Ab
      initio calculations have been performed for helping in the assignment of the
      spectral bands for both neutral excited states and ionic states.

PMID- 18331011
TI  - Use of effective core potential calculations for the conformational and
      vibrational study of platinum(II) anticancer drugs. cis
      Diamminedichloroplatinum(II) as a case study.
AB  - In the light of the recognized anticancer properties of cisplatin-type inorganic
      systems, the exact knowledge of their conformational preferences is of the utmost
      importance for understanding their biological activity. The present study reports
      the use of theoretical (quantum mechanical) calculations for achieving this goal.
      An alternative calculation method to the use of the AE basis sets, both accurate
      and computationally feasible, was presently tested for the conformational and
      vibrational study of cis-diamminedichloroplatinum(II). Effective core potentials
      (ECPs) were used, within the HF methodology and, within the B3LYP and mPW1PW DFT
      protocols. The DFT methods (particularly mPW1PW) were found to be the best choice
      for describing cDDP (as compared to the HF methodology).

PMID- 18331012
TI  - A microwave spectroscopic and quantum chemical study of 3-butyne-1-selenol
      (HSeCH2CH2C[triple bond]CH).
AB  - The microwave spectrum of 3-butyne-1-selenol has been studied by means of Stark
      modulation microwave spectroscopy and quantum chemical calculations employing the
      B3LYP/aug-cc-pVTZ and MP2/6-311++G(3df,3pd) methods. Rotational transitions
      attributable to the H80SeCH2CH2C[triple bond]CH and H78SeCH2CH2C[triple bond]CH
      isotopologues of two conformers of this molecule were assigned. One of these
      conformers possesses an antiperiplanar arrangement for the atoms Se-C-C-C, while
      the other is synclinal and seems to be stabilized by the formation of a weak
      intramolecular hydrogen bond between the hydrogen atom of the selenol group and
      the pi electrons of the CC triple bond. The energy difference between these
      conformers was determined to be 0.2(5) kJ/mol by relative intensity measurements,
      and the hydrogen-bonded form was slightly lower in energy.

PMID- 18331013
TI  - Experimental and computational investigation of gas-phase reaction of chlorine
      with n-propanol: observation of chloropropanol conformational isomerization at
      room temperature.
AB  - FTIR smog chamber techniques were used to measure k(Cl+n-C3H7OH) = (1.74 +/-
      0.15) x 10-10 and k(Cl+CH2ClCH2CH2OH) = (7.54 +/- 0.73) x 10-11 cm3 molecule-1 s
      1 in 700 Torr of N2 at 296 K. The reaction of Cl with n-C3H7OH gives CH3CH2CHOH,
      CH3CHCH2OH, and CH2CH2CH2OH radicals in yields of 60 +/- 5, 25 +/- 8, and 15 +/-
      3%, respectively. Neither CH3CH2CHClOH nor CH3CHClCH2OH is available
      commercially, and infrared spectra for the three chlorides CH3CH2CHClOH,
      CH3CHClCH2OH, and CH2ClCH2CH2OH were calibrated experimentally. MP2/6-31G(d,p)
      calculations were used to corroborate the experimental vibrational assignments.
      Analysis reveals that each geometric isomer possesses several structurally and
      spectroscopically distinct conformers arising from intramolecular hydrogen
      bonding and, in the case of CH3CH2CHClOH, negative hyperconjugation. These
      conformers interchange slowly enough to be distinguished within the room
      temperature vibrational spectrum. The experimentally observed vibrational spectra
      are well described by a Boltzmann-weighted superposition of the conformer
      spectra. As is typical of alpha-halogenated alcohols, CH3CH2CHClOH readily
      decomposes heterogeneously to propanal and HCl.

PMID- 18331014
TI  - Cooperativity in intramolecular bifurcated hydrogen bonds: an ab initio study.
AB  - Molecular orbital and density functional theory calculations are performed on
      some di- and tetrasubstituted derivatives of anthraquinone, dihydrophenazine, and
      acridone to investigate cooperativity in a pair of bifurcated hydrogen bonds
      occurring in the same molecule. The various structures were selected as
      convenient model systems for three-center hydrogen bonding of both H...A...H and
      A...H...A types. In the former type, the C=O moieties in anthraquinone and
      acridone act as bifurcated hydrogen bond acceptors, and substituted OH groups act
      as hydrogen bond donors. In the latter type, the N-H moieties in
      dihydrophenazine, acridones act as bifurcated hydrogen bond donors, and the
      carbonyl oxygens of substituted CHO groups act as hydrogen bond acceptors.
      Different indicators of cooperativity reveal that two intramolecular bifurcated
      hydrogen bonds simultaneously present in the same molecule significantly
      reinforce each other.

PMID- 18331015
TI  - Heterolytic bond dissociation in water: why is it so easy for C4H9Cl but not for
      C3H9SiCl?
AB  - The recently developed (Song, L.; Wu, W.; Zhang, Q.; Shaik, S. J. Phys. Chem. A
      2004, 108, 6017-6024) valence bond method coupled to a polarized continuum model
      (VBPCM) is used to address the long standing conundrum of the heterolytic
      dissociation of the C-Cl and Si-Cl bonds, respectively, in tertiary-butyl
      chloride and trimethylsilyl chloride in condensed phases. The method is used here
      to compare the bond dissociation in the gas phase and in aqueous solution. In
      addition to the ground state reaction profile, VB theory also provides the
      energies of the purely covalent and purely ionic VB structures as a function of
      the reaction coordinate. Accordingly, the C-Cl and Si-Cl bonds are shown to be of
      different natures. In the gas phase, the resonance energy arising from covalent
      ionic mixing at equilibrium geometry amounts to 42 kcal/mol for tertiary-butyl
      chloride, whereas the same quantity for trimethylsilyl chloride is significantly
      higher at 62 kcal/mol. With such a high value, the root cause of the Si-Cl
      bonding is the covalent-ionic resonance energy, and this bond belongs to the
      category of charge-shift bonds (Shaik, S.; Danovich, D.; Silvi, B.; Lauvergnat,
      D.; Hiberty, P. C. Chem.- Eur. J. 2005, 11, 6358). This difference between the C
      Cl and Si-Cl bonds carries over to the solvated phase and impacts the heterolytic
      cleavages of the two bonds. For both molecules, solvation lowers the ionic curve
      below the covalent one, and hence the bond dissociation in the solvent generates
      the two ions, Me3E+ Cl- (E = C, Si). In both cases, the root cause of the barrier
      is the loss of the covalent-ionic resonance energy. In the heterolysis reaction
      of Si-Cl, the covalent-ionic resonance energy remains large and fully contributes
      to the dissociation energy, thereby leading to a high barrier for heterolytic
      cleavage, and thus prohibiting the generation of ions. By contrast, the covalent
      ionic resonance energy is smaller for the C-Cl bond and only partially
      contributes to the barrier for heterolysis, which is consequently small, leading
      readily to ions that are commonly observed in the classical SN1 mechanism. Thus,
      the reluctance of R3Si-X molecules to undergo heterolysis in condensed phases and
      more generally the rarity of free silicenium ions under these conditions are
      experimental manifestations of the charge-shift character of the Si-Cl bond.

PMID- 18331016
TI  - Theoretical studies of solid bicyclo-HMX: effects of hydrostatic pressure and
      temperature.
AB  - On the basis of density functional theory (DFT) and molecular dynamics (MD), the
      structural, electronic, and mechanical properties of the energetic material
      bicyclo-HMX have been studied. The crystal structure optimized by the LDA/CA-PZ
      method compares well with the experimental data. Band structure and density of
      states calculations indicate that bicyclo-HMX is an insulator with the band gap
      of ca. 3.4 eV and the N-NO(2) bond is the reaction center. The pressure effect on
      the bulk structure and properties has been investigated in the range of 0-400
      GPa. The crystal structure and electronic character change slightly as the
      pressure increases from 0 to 10 GPa; when the pressure is over 10 GPa, further
      increment of the pressure determines significant changes of the structures and
      large broadening of the electronic bands together with the band gap decreasing
      sharply. There is a larger compression along the c-axis than along the a- and b
      axes. To investigate the influence of temperature on the bulk structure and
      properties, isothermal-isobaric MD simulations are performed on bicyclo-HMX in
      the temperature range of 5-400 K. It is found that the increase of temperature
      does not significantly change the crystal structure. The thermal expansion
      coefficients calculated for the model indicate anisotropic behavior with slightly
      larger expansion along the a- and c-axes than along the b-axis.

PMID- 18331017
TI  - Coupling of complex aromatic ring vibrations to solvent through hydrogen bonds:
      effect of varied on-ring and off-ring hydrogen-bonding substitutions.
AB  - In this study, we examine the coupling of a complex ring vibration to solvent
      through hydrogen-bonding interactions. We compare phenylalanine, tyrosine, l
      dopa, dopamine, norepinephrine, epinephrine, and hydroxyl-dl-dopa, a group of
      physiologically important small molecules that vary by single differences in H
      bonding substitution. By examination of the temperature dependence of infrared
      absorptions of these molecules, we show that complex, many-atom vibrations can be
      coupled to solvent through hydrogen bonds and that the extent of that coupling is
      dependent on the degree of both on- and off-ring H-bonding substitution. The
      coupling is seen as a temperature-dependent frequency shift in infrared spectra,
      but the determination of the physical origin of that shift is based on additional
      data from temperature-dependent optical experiments and ab initio calculations.
      The optical experiments show that these small molecules are most sensitive to
      their immediate H-bonding environment rather than to bulk solvent properties. Ab
      initio calculations demonstrate H-bond-mediated vibrational coupling for the
      system of interest and also show that the overall small molecule solvent
      dependence is determined by a complex interplay of specific interactions and bulk
      solvation characteristics. Our findings indicate that a full understanding of
      biomolecule vibrational properties must include consideration of explicit
      hydrogen-bonding interactions with the surrounding microenvironment.

PMID- 18331018
TI  - Vibrational energy relaxation of a hydrogen-bonded complex dissolved in a polar
      liquid via the mixed quantum-classical Liouville method.
AB  - The vibrational energy relaxation (VER) of the hydrogen stretch in a linear
      hydrogen-bonded complex dissolved in a polar solvent is studied. The study is
      based on the Azzouz-Borgis model [Azzouz, H.; Borgis, D. J. Chem. Phys. 1993, 98,
      7361], which is known to account for many important features of real hydrogen
      bonded systems, including ionic-to-covalent tautomerism and a broad distribution
      of hydrogen stretch frequencies. A description of VER in this strongly coupled
      system is considered, which consists of the following three consecutive steps:
      (1) solvation on the adiabatic excited vibrational surface; (2) nonadiabatic
      transition from the excited to the ground adiabatic vibrational surface; and (3)
      solvation on the adiabatic ground vibrational surface. The relaxation dynamics
      during those three steps were simulated via the mixed quantum-classical Liouville
      method, where the hydrogen is treated quantum-mechanically, while the other
      particles are treated in a classical-like manner. The solvation on the excited
      state surface was found to occur rapidly ( approximately 0.5 ps) and to involve
      energy exchange with both the intramolecular and intermolecular degrees of
      freedom. It was also found that, while energy is released to the solvent during
      the solvation of the covalent tautomer, the solvation of the ionic tautomer
      involves absorption of energy from the solvent. The decrease in the transition
      frequency during the solvation process also facilitates the nonadiabatic
      transitions, which occur rapidly ( approximately 0.8 ps) thereafter. The
      nonadiabatic transitions were shown to be induced by interactions with a large
      number of solvent molecules and to be relatively insensitive to their location
      relative to the complex. Finally, solvation on the ground-state surface was seen
      to occur on a time scale of approximately 1.0 ps and leads to nonequilibrium
      ionic and covalent subpopulations. Equilibration on the ground-state surface
      occurs on a significantly slower time scale ( approximately 7.6 ps). Our results
      shed new light on the problem of VER in strongly coupled condensed phase systems
      that lie outside the range of validity of the Landau-Teller formula.

PMID- 18331019
TI  - A differential fluctuation theorem.
AB  - We derive a nonequilibrium thermodynamics identity (the "differential fluctuation
      theorem") that connects forward and reverse joint probabilities of nonequilibrium
      work and of arbitrary generalized coordinates corresponding to states of
      interest. This identity allows us to estimate the free energy difference between
      domains of these states. Our results follow from a general symmetry relation
      between averages over nonequilibrium forward and backward path functions derived
      by Crooks [Crooks, G. E. Phys. Rev. E 2000, 61, 2361-2366]. We show how several
      existing nonequilibrium thermodynamic identities can be obtained directly from
      the differential fluctuation theorem. We devise an approach for measuring
      conformational free energy differences, and we demonstrate its applicability to
      the analysis of molecular dynamics simulations by estimating the free energy
      difference between two conformers of the alanine dipeptide model system. We
      anticipate that these developments can be applied to the analysis of laboratory
      experiments.

PMID- 18331020
TI  - Surfactant-assisted alignment of ZnO nanocrystals to superstructures.
AB  - Self-organization of ZnO nanoparticles into various superstructures (sheet,
      platelet, ring) has been achieved with the assistance of micelles formed by
      surfactant cetyltrimethylammonium bromide (CTAB) under one-pot condition. The
      CTAB-modified zinc hydroxy double salt (Zn-HDS) mesocrystals act as intermediates
      to form ZnO hexagonal superstructures at temperatures as low as 50 degrees C. The
      decomposition temperature of Zn-HDS mesocrystals is much lower than that of the
      corresponding bulk crystals because the organic additive CTAB effectively
      decreases the degree of crystallinity. Taking advantage of temperature-induced
      phase transformation of micelles, two-stage self-organization can form ZnO
      platelets and ring mesocrystals, that is, ZnO ellipsoidal superstructures formed
      through vertical attachment on (0001) facets of basic units can further assemble
      to form ZnO platelets and rings through vertical attachment on (0001) facets of
      ZnO ellipsoidal superstructures. The structural transformation of micelles as
      shape templates can offer a new route for self-assembly of nonspherical colloids
      into three-dimensional photonic crystals. ZnO sheet, ring, and platelet
      mesocrystals with a high population of polar Zn-(0001) plane are expected to have
      high photocatalytic activity.

PMID- 18331021
TI  - Ab initio QM/MM studies of the phosphoryl transfer reaction catalyzed by PEP
      mutase suggest a dissociative metaphosphate transition state.
AB  - The interconversion between phosphoenolpyruvate (PEP) and phosphonopyruvate (P
      pyr) catalyzed by PEP mutase is investigated using an ab initio QM/MM method with
      the QM region treated at the B3LYP/6-31G* level of theory. Two-dimensional
      minimum energy path calculations were carried out for both the wild-type enzyme
      and the N122A mutant. The calculations suggest a dissociative transition state
      featuring metaphosphate and Mg(2+)-coordinating pyruvate enolate, stabilized by
      an extensive hydrogen bond network involving Asn122, Ser123, Arg159, His190,
      Ser46, and Leu48. It is also found that a substantial conformational change in
      the pyruvyl group is required for the interconversion.

PMID- 18331022
TI  - Thermodynamic interactions in double-network hydrogels.
AB  - Double-network hydrogels (DN-gels) prepared from the combination of a moderately
      cross-linked anionic polyelectrolyte (PE) and an uncross-linked linear polymer
      solution (NP) exhibit mechanical properties such as fracture toughness that are
      intriguingly superior to that of their individual constituents. The scheme of
      double-network preparation, however, is not equally successful for all
      polyelectrolyte/neutral polymer pairs. A successful example is the combination of
      poly(2-acrylamido-2-methyl-1-propane sulfonic acid) (PAMPS) cross-linked network
      and linear polyacrylamide (PAAm), which results in DN-gels with fracture strength
      under compression approaching that of articular cartilage ( approximately 20
      MPa). Small-angle neutron scattering was used to determine the thermodynamic
      interaction parameters for PAMPS and PAAm in water as a first step to elucidate
      the molecular origin responsible for this superior property. Measurements on
      PAMPS/PAAm DN-gels and their solution blend counterparts indicate that the two
      polymers interact favorably with each other while in water. This favorable
      PAMPS/PAAm interaction given by the condition chi(PE-NP) < chi(PE-water) <chi(NP
      water), where chi is the Flory-Huggins interaction parameter, is consistent with
      some of the salient features of the DN structure revealed by SANS, and it may
      also contribute to the ultimate mechanical properties of DN-gels.

PMID- 18331023
TI  - Time-resolved studies of energy transfer from meso-tetrakis(N-methylpyridinium-4
      yl)- porphyrin to 3,3'-diethyl-2,2'-thiatricarbocyanine iodide along
      deoxyribonucleic acid Chain.
AB  - The excitation energy transfer from meso-tetrakis(N-methylpyridinium-4
      yl)porphyrin (TMPyP) to 3,3'-diethyl-2,2'-thiatricarbocyanine iodide (DTTCI)
      along the deoxyribonucleic acid (DNA) double strand was investigated by the
      steady-state absorption and fluorescence measurements and time-resolved
      fluorescence measurements. The steady-state fluorescence spectra showed that the
      near-infrared fluorescence of DTTCI was strongly enhanced up to 86 times due to
      the energy transfer from the excited TMPyP molecule in DNA buffer solution.
      Furthermore, we elucidated the mechanism of fluorescence quenching and
      enhancement by the direct observation of energy transfer using the time-resolved
      measurements. The fluorescence quenching of TMPyP chiefly consists of a static
      component due to the formation of complex and dynamic components due to the
      excitation energy transfer. In a heterogeneous one-dimensional system such as a
      DNA chain, it was proved that the energy transfer process only carries out within
      the critical distance based on the Forster theory and within a threshold value
      estimated from the modified Stern-Volmer equation. The present results showed
      that DNA chain is one of the most powerful tools for nanoassemblies and will give
      a novel concepts of material design.

PMID- 18331024
TI  - Vapor pressure and density of thermotropic liquid crystals: MBBA, 5CB, and novel
      fluorinated mesogens.
AB  - The vapor pressures and densities of six thermotropic liquid crystal-forming
      molecules (mesogens) have been determined experimentally as functions of
      temperature. The ubiquitous mesogenic compounds n-(4-methoxybenzylidene)-4
      butylaniline (MBBA) and 4'-cyano-4-n-pentylbiphenyl (5CB), which both exhibit
      room-temperature nematic phases, are examined in this study, as are a number of
      trifluorinated bicyclohexyl and cyclohexylbiphenyl derivatives which find modern
      use in display applications. Although thermotropic mesogens are of prime
      importance in modern optoelectronic technologies, there is a scarcity of reliable
      saturation pressure data for such systems. An apparatus suitable for measurements
      of vapor pressures between 0.1 and 1333 Pa in the temperature range 298-523 K has
      been constructed. The adequacy of the apparatus has been verified by measurements
      on n-hexadecane at temperatures between 304 and 372 K, corresponding to vapor
      pressures between 0.4 and approximately 100 Pa. To our knowledge, our
      measurements represent the first reliable data for the saturation pressure of the
      fluid phase of these types of thermotropic compounds; we show that existing data
      for MBBA is thermodynamically inconsistent. The densities of the fluid phases of
      these compounds are also measured by means of a glass pycnometer at temperatures
      between 293 and 368 K.

PMID- 18331025
TI  - Aquation of the ruthenium-based anticancer drug NAMI-A: a density functional
      study.
AB  - We carried out density functional theory (DFT) calculations to investigate the
      thermodynamics and the kinetics of the double aquation reaction of the anticancer
      drug NAMI-A. Three explicit water molecules were included in the calculations to
      improve the PB solvation energies. Our calculations show that the chloride
      substitution reactions on the considered Ru(III) octahedral complex follow a
      dissociative interchange mechanism, I(d), passing through a loose heptacoordinate
      transition state. We calculated an activation enthalpy and free energy for the
      first aquation step of 101.5 and 103.7 kJ mol(-1), respectively, values that are
      in good agreement with the available experimental results. The activation
      enthalpy and free energy for the second aquation step were found significantly
      higher, 118.7 and 125.0 kJ mol(-1), again in agreement with the experimental
      evidence indicating a slower rate for the second aquation.

PMID- 18331026
TI  - Redox chemistry of the triplet complex (PNP)Co(I).
AB  - Reaction of PNPCo, where PNP is (tBu2PCH2SiMe2)2N-, with the persistent radical
      galvinoxyl, G, gives PNPCoIIG, a nonplanar S = 3/2 species. Reaction with PhCH2Cl
      or with 0.5 mol I2 gives PNPCoX (X = Cl or I, respectively), but additional I2,
      seeking CoIII, gives instead oxidation at phosphorus:
      (tBu2P(I)CH2SiMe2NSiMe2CH2PtBu2)CoI2. Hydrogen-atom transfer reagents fail to
      give PNPCoH, but H2 gives instead PNPCo(H)2, a result rationalized
      thermodynamically based on DFT calculations. Multiple equiv of PhSiH3 give a
      product of Co(V), where N/SiPh and P/Si bonds have formed. N2CH(SiMe3) gives a
      1:1 adduct of PNPCo, whose metric parameters suggest partial oxidation above CoI;
      N2CHPh gives a 1:1 adduct but with very different spectroscopic features. PhN3
      reacts fast, via several intermediates detected below 0 degrees C, to finally
      release N2 and form a CoI product where one phosphorus has been oxidized,
      PN(P=NPh)Co. Whereas PNPCo(N3) resists loss of N2 on heating, one electron
      oxidation gives a rapid loss of N2, and the remaining nitride nitrogen is quickly
      incorporated into the chelate ligand, giving [tBu2PCH2SiMe2NSiMe2NP(tBu2)=CH2Co].
      O2 or PhI=O generally gives products where one or both phosphorus centers are
      converted to its oxide, bonded to cobalt.

PMID- 18331027
TI  - Topochemical 3D polymerization of C60 under high pressure at elevated
      temperatures.
AB  - Fullerene C60 monomer crystals were compressed to a face-centered cubic (fcc)
      phase with a lattice parameter of a = 11.93(5) A and a micro-Vickers hardness of
      4500 kg/mm2 using high-pressure and high-temperature conditions of 15 GPa at 500
      600 degrees C. The hardness is compatible with that of cubic boron nitride (c
      BN), suggesting the formation of a 3D C60 polymer. The single-crystal X-ray
      structural analysis revealed that each C60 molecule in the polymer was linked to
      the 12 nearest neighbors by [2+2] cycloaddition between the common pentagon
      hexagon (56) edges. However, ab initio geometry optimization and molecular
      dynamics calculations suggested that the 3D polymer should have a rhombohedral
      structure with the space group of R containing [3+3] cycloaddition between the
      pentagons of C60 molecules within the plane perpendicular to the 3-fold axis. The
      higher apparent symmetry of fcc was observed as an averaged structure of
      different orientations of the rhombohedral structure. The R structure can be
      derived by only a slight rotation of each C60 unit in the (111) plane of the fcc
      structure. The band-structure calculation suggested that the 3D polymer (R) was a
      semiconductor; the activation energy for the electrical conductivity was
      experimentally determined to be 0.25 eV at 550 K.

PMID- 18331028
TI  - Iron complexes of dendrimer-appended carboxylates for activating dioxygen and
      oxidizing hydrocarbons.
AB  - The active sites of metalloenzymes are often deeply buried inside a hydrophobic
      protein sheath, which protects them from undesirable hydrolysis and
      polymerization reactions, allowing them to achieve their normal functions. In
      order to mimic the hydrophobic environment of the active sites in bacterial
      monooxygenases, diiron(II) compounds of the general formula [Fe2([G-3]COO)4(4
      RPy)2] were prepared, where [G-3]COO- is a third-generation dendrimer-appended
      terphenyl carboxylate ligand and 4-RPy is a pyridine derivative. The dendrimer
      environment provides excellent protection for the diiron center, reducing its
      reactivity toward dioxygen by about 300-fold compared with analogous complexes of
      terphenyl carboxylate ([G-1]COO-) ligands. An FeIIFeIII intermediate was
      characterized by electronic, electron paramagnetic resonance, Mossbauer, and X
      ray absorption spectroscopic analyses following the oxygenation of [Fe2([G
      3]COO)4(4-PPy)2], where 4-PPy is 4-pyrrolidinopyridine. The results are
      consistent with the formation of a superoxo species. This diiron compound, in the
      presence of dioxygen, can oxidize external substrates.

PMID- 18331029
TI  - Pi*-pi* bonding interactions generated by halogen oxidation of zirconium(IV)
      redox-active ligand complexes.
AB  - The new complex, [Zr(pda)2]n (1, pda2- = N,N'-bis(neo-pentyl)-ortho
      phenylenediamide, n = 1 or 2), prepared by the reaction of 2 equiv of pdaLi2 with
      ZrCl4, reacts rapidly with halogen oxidants to afford the new product ZrX2(disq)2
      (3, X = Cl, Br, I; disq- = N,N'-bis(neo-pentyl)-ortho-diiminosemiquinonate) in
      which each redox-active ligand has been oxidized by one electron. The oxidation
      products 3a-c have been structurally characterized and display an unusual
      parallel stacked arrangement of the disq- ligands in the solid state, with a
      separation of approximately 3 A. Density functional calculations show a bonding
      type interaction between the SOMOs of the disq- ligands to form a unique HOMO
      while the antibonding linear combination forms a unique LUMO. This orbital
      configuration leads to a closed-shell-singlet ground-state electron configuration
      (S = 0). Temperature-dependent magnetism measurements indicate a low-lying
      triplet excited state at approximately 750 cm-1. In solution, 3a-c show strong
      disq--based absorption bands that are invariant across the halide series. Taken
      together these spectroscopic measurements provide experimental values for the one
      and two-electron energies that characterize the pi-stacked bonding interaction
      between the two disq- ligands.

PMID- 18331030
TI  - Atomic structure of a short alpha-helix stabilized by a main chain hydrogen-bond
      surrogate.
AB  - Herein we report the 1.15 A X-ray crystal structure of a short alpha-helix in
      which the N-terminal i and i + 4 main chain hydrogen bond is replaced with a
      carbon-carbon bond. The structure shows that the hydrogen-bond surrogate (HBS)
      derived alpha-helix truly resembles the structure of canonical alpha-helices and
      provides unequivocal support for our helix nucleation strategy.

PMID- 18331031
TI  - Determination of the origin of stereoselectivity in multiple-transition-state
      reactions using DFT calculations: enantioselective synthesis of homoallylic
      alcohols from aliphatic methyl ketones via an auxiliary-mediated allylation.
AB  - Computational investigations on the highly stereoselective allylation of butanone
      in the presence of a chiral norpseudoephedrine-derived auxiliary have been
      performed. They suggest an SN1-type mechanism via the attack of
      allyltrimethylsilane to an intermediately formed oxocarbenium ion. The
      identification of preferred transition states (TSs) leads to a straightforward
      rationalization of the observed selectivity which can be extended to analogues of
      the auxiliary. A screening process has been devised to select 61 potentially
      relevant TSs from a total of almost 300 theoretically possible TSs. Final results
      were obtained from gas-phase calculations employing the B3LYP/6-31+G(d) level of
      theory as well as in dichloromethane solution using the B3LYP/6
      311++G(2d,p)//B3LYP/6-31+G(d) level of theory in combination with polarizable
      continuum model and the UAKS set of radii. The agreement of theoretically
      predicted and experimentally observed selectivities is very good in both cases.
      However, the relative energy differences for several relevant TSs differ
      significantly when going from gas phase to solution, thus illustrating the
      necessity of performing calculations in solution to draw correct conclusions.

PMID- 18331032
TI  - Computational modeling of the optical rotation of amino acids: a new look at an
      old rule for pH dependence of optical rotation.
AB  - The molar rotation of a solution of a natural alpha amino acid is changed in the
      positive direction by addition of a strong acid. Three decades ago, an attempt to
      rationalize this old rule, named for Clough, Lutz, and Jirgensons (CLJ), was made
      by assigning circular dichroism octants for overlapping carbonyl n to pi*
      transitions. Modern quantum chemical methods allow us to take a new look at this
      phenomenon. Time-dependent density functional theory was used to model the
      electronic structure and transitions responsible for CLJ. We show that sector
      rules originally developed for circular dichroism (CD) can be applied to the
      optical rotation in this case, but with some restrictions, and with great
      caution, due to the change of the overall charge of the acids upon protonation
      and the distortion of the COO- chromophore in the zwitterions. We have prepared
      sector maps based on first-principles computations to study the correspondence
      between CD and optical rotation for zwitterionic and protonated l-amino acid
      chromophores. The CLJ effect is correctly obtained from the computations for all
      12 amino acids studied in this work.

PMID- 18331033
TI  - Linear assemblies of magnetic nanoparticles as MRI contrast agents.
AB  - Using a one-step procedure we have prepared magnetic fluids comprising of
      polyelectrolyte stabilized magnetite nanoparticles. These nanocomposites are
      comprised of linear, chain-like assemblies of magnetic nanoparticles, which can
      be aligned in parallel arrays by an external magnetic field. We have shown the
      potential use of these materials as contrast agents by measuring their MR
      response in live rats. The new magnetic fluids have demonstrated good
      biocompatibility and potential for in vivo MRI diagnostics.

PMID- 18331034
TI  - Half-metallicity in edge-modified zigzag graphene nanoribbons.
AB  - Graphene is an important material with potential application in spintronics. Edge
      modified zigzag graphene nanoribbons (ZGNR) are investigated with density
      functional theory. The modifications are realized by saturating the dangling edge
      bonds by different terminal groups, such as H, NH2, NO2, and CH3. Such
      modification has a significant impact on the ZGNR electronic structure. Half
      metallicity is observed when ZGNR is terminated by NO2 groups at one edge and by
      CH3 groups on the other side. Free energy analysis suggests that edge
      modification is a practical way in experiment to realize half-metallicity.

PMID- 18331035
TI  - Construction of a chiral quaternary carbon center by indium-catalyzed asymmetric
      alpha-alkenylation of beta-ketoesters.
AB  - Construction of a nonracemic all-carbon quaternary stereocenter at the alpha
      position of beta-ketoesters was achieved by way of an indium(III)-catalyzed
      diastereoselective alpha-alkenylation reaction of chiral enamines with 1-alkynes.
      The enamine bearing a chiral auxiliary derived from l-isoleucine was added to the
      alkyne to give an alpha-alkenylated product in excellent yield and with a
      stereoselectivity better than 90% ee. One can ascribe the high selectivity to a
      chelate intermediate involving the auxiliary and the metal atom and the high
      yield to efficient interactions between the indium(III) atom and the alkyne. The
      selectivity increased as the reaction temperature was raised to 120 degrees C and
      decreased at higher temperatures.

PMID- 18331036
TI  - Azo supramolecules on Au(111) with controlled size and shape.
AB  - Using a subtle balance between weak intermolecular C-H...N hydrogen bonds and
      molecule-surface interactions, supramolecules of azobenzene-related molecules on
      Au surfaces were prepared. For analysis, modeling based on first-principles
      calculations was performed.

PMID- 18331037
TI  - Alkyl peroxides reveal the ring opening mechanism of verdoheme catalyzed by heme
      oxygenase.
AB  - Heme oxygenase (HO) catalyzes heme catabolism through three successive
      oxygenation steps where the substrate heme itself activates O2. Although a rate
      determining step of the HO catalysis is considered as third oxygenation, the
      verdoheme degradation mechanism has been the least understood in the HO
      catalysis. In order to discriminate three possible pathways proposed for the
      verdoheme ring-opening, we have examined reactions of the verdoheme-HO-1 complex
      with alkyl peroxides, namely MeOOH. Under reducing conditions, the MeOOH reaction
      afforded two novel products whose absorption spectra are similar to but slightly
      different from that of biliverdin. HPLC, ESI-MS, and NMR analysis show that these
      products are 1- and 19-methoxy-deoxy-biliverdins. The addition of a methoxy group
      at one end of the linear tetrapyrrole unambiguously indicates transient formation
      of the Fe-OOMe intermediate and rearrangement of its terminal methoxy group to
      the alpha-pyrrole carbon. The corresponding OH transfer of the Fe-OOH species is
      highly probable in the H2O2-dependent verdoheme degradation and is likely to be
      the case in the O2-dependent reaction catalyzed by HO as well.

PMID- 18331038
TI  - Spontaneous self-assembly of metal-organic cationic nanocages to form
      monodisperse hollow vesicles in dilute solutions.
AB  - In this communication we report the unprecedented spontaneous self-assembly of
      cationic nanoporous metal-organic coordination cages (nanocages) into giant
      hollow vesicle-like structures in polar solvents. Such highly soluble nanocages
      (macrocations) have separated hydrophobic regions. However, their assembly is not
      due to hydrophobic interactions but the counterion-mediated attractions, very
      similar to the unique self-assembly of polyoxometalate macroanions into single
      layer, spherical blackberry structures, as characterized by laser light
      scattering and TEM studies. This is the first study on the solution behavior of
      metal-organic nanocages and also the first report on the self-assembly of soluble
      macrocations. Therefore, the blackberry structure is likely to be a universal
      type of self-assembly for soluble macroions. In addition, the self-assembled
      nanocages can provide blackberry structures a wide range of organic
      functionalities that are impossible to reach with purely inorganic systems, which
      may open the door to many types of applications.

PMID- 18331039
TI  - Pressure response of three-dimensional cyanide-bridged bimetallic magnets.
AB  - Effects of pressure on the structures and magnetic properties of three types of 3
      D cyanide-bridged bimetallic coordination polymer magnets, MnIICrIII ferrimagnet
      [Mn(en)]3[Cr(CN)6]2.4H2O (1; en = ethylenediamine), NiIICrIII ferromagnet
      [Ni(dipn)]3[Cr(CN)6]2.3H2O (2; dipn = N,N-di(3-aminopropyl)amine), and NiIIFeIII
      ferromagnet [Ni(dipn)]2[Ni(dipn)(H2O)][Fe(CN)6]2.11H2O (3), were systematically
      examined under hydrostatic pressure up to 19.8 GPa using a piston-cylinder-type
      pressure cell and a diamond anvil cell. The ferrimagnet 1 showed the reversible
      crystalline-to-amorphous-like phase change, and the magnetic phase transition
      temperature (TC) was reversibly changed from 69 K at 0 GPa to 126 K at 4.7 GPa.
      At higher pressure, the net magnetization was suppressed with increasing
      pressure, and the magnetic state at 19.8 GPa was assumed to be paramagnetic. The
      initial ferrimagnetic phase of 1 was not recovered after releasing the pressure
      from 19.8 GPa. The magnetic phase of 2 was reversibly converted between
      ferromagnetic and paramagnetic-like phase in the range 0 </= P </= 4.7 GPa while
      maintaining its crystallinity. The porous ferromagnet 3 was easily amorphized and
      irreversibly lost the ferromagnetic phase under low pressure (P </= 1.0 GPa). The
      flexible cyanide-bridged magnetic frameworks demonstrate well the pressure
      response as a reflection of differences in the magnetic structure and the
      framework strength in the GPa range.

PMID- 18331040
TI  - Biosynthesis and structures of cyclomarins and cyclomarazines, prenylated cyclic
      peptides of marine actinobacterial origin.
AB  - Two new diketopiperazine dipeptides, cyclomarazines A and B, were isolated and
      characterized along with the new cyclic heptapeptide cyclomarin D from the marine
      bacterium Salinispora arenicola CNS-205. These structurally related cyclic
      peptides each contain modified amino acid residues, including derivatives of N
      (1,1-dimethylallyl)-tryptophan and delta-hydroxyleucine, which are common in the
      di- and heptapeptide series. Stable isotope incorporation studies in Streptomyces
      sp. CNB-982, which was first reported to produce the cyclomarin anti-inflammatory
      agents, illuminated the biosynthetic building blocks associated with the major
      metabolite cyclomarin A, signifying that this marine microbial peptide is
      nonribosomally derived largely from nonproteinogenic amino acid residues. DNA
      sequence analysis of the 5.8 Mb S. arenicola circular genome and PCR-targeted
      gene inactivation experiments identified the 47 kb cyclomarin/cyclomarazine
      biosynthetic gene cluster (cym) harboring 23 open reading frames. The cym locus
      is dominated by the 23 358 bp cymA, which encodes a 7-module nonribosomal peptide
      synthetase (NRPS) responsible for assembly of the full-length cyclomarin
      heptapeptides as well as the truncated cyclomarazine dipeptides. The
      unprecedented biosynthetic feature of the megasynthetase CymA to synthesize
      differently sized peptides in vivo may be triggered by the level of beta
      oxidation of the priming tryptophan residue, which is oxidized in the cyclomarin
      series and unoxidized in the cyclomarazines. Biosynthesis of the N-(1,1-dimethyl
      2,3-epoxypropyl)-beta-hydroxytryptophan residue of cyclomarin A was further
      illuminated through gene inactivation experiments, which suggest that the
      tryptophan residue is reverse prenylated by CymD prior to release of the cyclic
      peptide from the CymA megasynthetase, whereas the cytochrome P450 CymV installs
      the epoxide group on the isoprene of cyclomarin C post-NRPS assembly. Last, the
      novel amino acid residue 2-amino-3,5-dimethylhex-4-enoic acid in the cyclomarin
      series was shown by bioinformatics and stable isotope experiments to derive from
      a new pathway involving condensation of isobutyraldehyde and pyruvate followed by
      S-adenosylmethionine methylation. Assembly of this unsaturated, branched amino
      acid is unexpectedly related to the degradation of the environmental pollutant 3
      (3-hydroxyphenyl)propionic acid.

PMID- 18331041
TI  - Two-photon fluorescent turn-on probe for lipid rafts in live cell and tissue.
AB  - We report a new two-photon fluorescence turn-on probe 6-[(E)-3-oxo-1-dodecenyl]-2
      [N-methyl-N-(carboxymethyl)amino]naphthalene (CL2) that is designed specifically
      for visualizing lipid rafts in living cells and tissues. This probe emits much
      brighter two-photon excited fluorescence in lipid rafts than in non-raft domains
      and allows direct visualization of the lipid rafts in the live cells and
      pyramidal neuron layer of the CA1 region at a depth of 100-250 mum in live
      tissues using two-photon microscopy.

PMID- 18331042
TI  - Regioselective activation of oxo ligands in functionalized dawson
      polyoxotungstates.
AB  - The organic side chain of tin-substituted Dawson polyoxotungstates alpha1- and
      alpha2-[P2W17O61{SnCH2CH2COOH}]7- can be used to direct regioselective acylations
      of oxo ligands in the inorganic backbone, which was examined both experimentally
      and computationally. Acylation of the oxo ligand gave exalted electrophilicity to
      the acyl moiety, and the compounds that were obtained led to direct ligation of
      POMs to complex organic molecules.

PMID- 18331043
TI  - A facile and patternable method for the surface modification of carbon nanotube
      forests using perfluoroarylazides.
AB  - A facile patterning method for the functionalization of vertically aligned carbon
      nanotubes is described. Modification of the surface of nanotube forests with
      hydrophilic, hydrophobic, or polymerizable small molecules was achieved via UV
      triggered attachment of perfluoroarylazides. Multiple functionalizations of the
      tube surface can be achieved. Macro- and micropatterning of forest substrates
      were demonstrated. Superhydrophobic surfaces containing superhydrophilic regions
      were prepared.

PMID- 18331044
TI  - Modular synthesis of functionalized benzosiloles by tin-mediated cyclization of
      (o-Alkynylphenyl)silane.
AB  - Trimethylstannyllithium promotes cyclization of (o-alkynylphenyl)silane into a 3
      stannylbenzosilole, via addition to the triple bond followed by intramolecular
      cyclization in a cascade fashion. This intermediate can be functionalized with
      either electrophiles or nucleophiles to allow modular synthesis of 2,3
      disubstituted benzosiloles. One of these compounds, a phenylene-bis(benzosilole)
      compound, shows electron drift mobility as high as 6 x 10-4 cm2/Vs in an
      amorphous film, making this class of compounds promising electronic materials for
      organic light emitting devices and organic photovoltaic cells.

PMID- 18331045
TI  - Convenient synthesis of branched-chain glycosamines by radical addition of
      nitromethane to glycals.
AB  - Radical addition-reduction-acetylation is the simple three-step sequence for the
      synthesis of branched-chain glycosamines 3 from glycals 1 and nitromethane (2).
      The intermediary formed 2-C-nitromethyl-pyranosides are valuable precursors for
      the synthesis of C-2 branched disaccharides.

PMID- 18331046
TI  - Realization of anti-SN2' selective allylation of 4-cyclopentene-1,3-diol
      monoester with aryl- and alkenyl-zinc reagents.
AB  - Anti-SN2' mode of allylation of the monoester of 4-cyclopentene-1,3-diol with
      aryl and alkenyl anions was achieved, for the first time, with the MeOCH2CO2-
      group as a leaving group to which R-ZnBr and CuCl (as a catalyst) were best
      fitted. The aryl groups successfully installed were Ph, o- and p-MeC6H4, o
      MOMOC6H4, o-MeOC6H4, and p-F-C6H4, while cis and trans alkenyl groups were
      attached with retention of the olefinic stereochemistries.

PMID- 18331047
TI  - Asymmetric synthesis of cis- and trans-2,5-disubstituted pyrrolidines from 3-oxo
      pyrrolidine 2-phosphonates: synthesis of (+)-preussin and analogs.
AB  - Pyrrolidine enones, derived from 3-oxo pyrrolidine 2-phosphonates and a HWE
      reaction with aldehydes, on Luche reduction give pyrrolidine allylic alcohols.
      The alcohols on hydrogenation (Pd/H2) give cis-2,5-disubstituted pyrrolidines and
      on treatment with TFA-NaBH3CN undergo a hydroxy directed reduction to trans-2,5
      disubstituted pyrrolidines.

PMID- 18331048
TI  - One step cascade synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles.
AB  - A Lewis base-catalyzed three-component cascade reaction was developed for the
      synthesis of 4,5-disubstituted-1,2,3-(NH)-triazoles. More than 25 new (NH)
      triazoles were prepared in good to excellent yields under mild conditions. The
      availability of the C-4 vinyl group allows easy conversion into other triazole
      derivatives.

PMID- 18331049
TI  - Optimization of the media ingredients for cutinase production from Colleotrichum
      lindemuthianum using mixture design experiments.
AB  - Optimal concentrations of yeast extract, glucose and potassium phosphate in the
      fermentation medium have been identified for the maximum cutinase production from
      the fungi Colleotrichum lindemuthianum. A simplex lattice experimental design for
      mixtures was used to identify concentration ranges that yield maximum production.
      Three sets of experiments were performed all involving three ingredients. The
      sets of experiments differ in the number of concentration levels considered. In
      the first set we consider four concentration levels (i.e., 0%, 33%, 67%, 100%),
      and in the second and third sets we consider five and six levels, respectively.
      Results showed that the interactions among the nutrient ingredients are best
      captured when five- and six-level experiments are carried out. An algorithm has
      been proposed in this study to design the optimal medium. Various models were
      also developed to predict the enzyme production, and it is concluded that the
      cubic model obtained using six-level experimental data gives the best model. The
      study also highlighted the synergistic interaction between yeast extract and
      glucose toward cutinase production.

PMID- 18331050
TI  - Sub-lethal levels of electric current elicit the biosynthesis of plant secondary
      metabolites.
AB  - Many secondary metabolites that are normally undetectable or in low amounts in
      healthy plant tissue are synthesized in high amounts in response to microbial
      infection. Various abiotic and biotic agents have been shown to mimic
      microorganisms and act as elicitors of the synthesis of these plant compounds. In
      the present study, sub-lethal levels of electric current are shown to elicit the
      biosynthesis of secondary metabolites in transgenic and non-transgenic plant
      tissue. The production of the phytoalexin (+)-pisatin by pea was used as the main
      model system. Non-transgenic pea hairy roots treated with 30-100 mA of electric
      current produced 13 times higher amounts of (+)-pisatin than did the non-elicited
      controls. Electrically elicited transgenic pea hairy root cultures blocked at
      various enzymatic steps in the (+)-pisatin biosynthetic pathway also accumulated
      intermediates preceding the blocked enzymatic step. Secondary metabolites not
      usually produced by pea accumulated in some of the transgenic root cultures after
      electric elicitation due to the diversion of the intermediates into new pathways.
      The amount of pisatin in the medium bathing the roots of electro-elicited roots
      of hydroponically cultivated pea plants was 10 times higher 24 h after
      elicitation than in the medium surrounding the roots of non-elicited control
      plants, showing not only that the electric current elicited (+)-pisatin
      biosynthesis but also that the (+)-pisatin was released from the roots.
      Seedlings, intact roots or cell suspension cultures of fenugreek (Trigonella
      foenum-graecum), barrel medic, (Medicago truncatula), Arabidopsis thaliana, red
      clover (Trifolium pratense) and chickpea (Cicer arietinum) also produced
      increased levels of secondary metabolites in response to electro-elicitation. On
      the basis of our results, electric current would appear to be a general elicitor
      of plant secondary metabolites and to have potential for application in both
      basic and commercial research.

PMID- 18331051
TI  - Dramatic effects of halogen substitution and solvent on the rates and mechanisms
      of nucleophilic substitution reactions of aziridines.
AB  - In a previous study we reported that fluorine substitution at the carbon
      positions of aziridine results in profound enhancements of the rate of reaction
      with ammonia, a typical nucleophile, in the gas phase. In this study the
      investigation is extended to include chloro- and bromoaziridines. Because
      syntheses are largely performed in the condensed phase, the present computational
      investigation [(MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level] was conducted
      with three typical solvents that cover a wide range of polarity: THF, CH3CN, and
      H2O. Nucleophiles can react with haloaziridines 1 by displacing a substituted
      amide ion by means of an SN2 mechanism (pathway a), producing 1,2
      diaminohaloethanes (from the initially formed dipolar species 2). Alternatively,
      a rearrangement mechanism involving rate-determining departure of a halide ion
      (pathway b) to form an imidoyl halide, 3, is possible. Transition-state theory
      was used to compute relative reaction rates of these mechanistic possibilities
      and to assess the role of the halogen substituents and the reaction solvent. Gas
      phase results provided the basis of mechanistic insights that were more apparent
      in the absence of intermolecular interactions. Fluoroaziridines were found to
      react at accelerated rates relative to aziridine exclusively by means of the a
      Menshutkin-type mechanism (SN2) in each solvent tested, while the reactions of
      the chloro- and bromoaziridines could be directed toward 2 in the highly nonpolar
      solvent, cyclohexane, or toward 3 in the more polar solvents. An assessment is
      made of the feasibility of using this chemistry of the haloazirdines in the
      synthetic laboratory.

PMID- 18331052
TI  - Umpolung reactivity of difluoroenol silyl ethers with amines and amino alcohols.
      application to the synthesis of enantiopure alpha-difluoromethyl amines and amino
      acids.
AB  - Difluoroenol silyl ethers, produced in situ from acylsilanes and CF3TMS, react as
      electrophiles with amines to give difluoroimines, via the corresponding
      hemiaminal adduct, as evidenced by 19F NMR spectroscopy. Reaction with (R)
      phenylglycinol led to 2-difluoromethyloxazolidines. After separation of the
      diastereomers, reduction with LAH and Strecker-type synthesis gave enantiopure
      alpha-difluoromethylamines and alpha-difluoromethyl-alpha-amino acids,
      respectively.

PMID- 18331053
TI  - Synthesis of indenol- and azulenol derivatives via platinum dichloride-catalyzed
      intramolecular hydroxy- or alkoxycyclization of cyclic dienynes.
AB  - Platinum dichloride-catalyzed hydroxy- or alkoxycyclization of cyclohexadienynes
      gives indenol derivatives, whereas hydroxy- or alkoxycyclization of
      cycloheptadienynes produces azulenol derivatives. The cyclization reaction
      proceeds via a cyclopropyl platinacarbene intermediate and allows for the direct
      stereocontrol of three contiguous stereogenic centers of the fused bicyclic
      skeletons. The transient reactive intermediate obtained from PtCl2-catalyzed
      cyclization reaction of a cyclohexadienyndiol can be trapped intramolecularly by
      a hydroxyl group to afford an oxatricyclo[5.4.0.04,8]undecane ring skeleton with
      extreme diastereoselectivity.

PMID- 18331054
TI  - Synthesis and spin-trapping properties of a new spirolactonyl nitrone.
AB  - Spin trapping using electron paramagnetic resonance (EPR) spectroscopy is
      commonly employed for the identification of transient radicals in chemical and
      biological systems. A spirolactonyl-nitrone with rigid H-bond acceptor, 7-oxa-1
      azaspiro[4.4]non-1-en-6-one 1-oxide, CPCOMPO, has been synthesized and
      characterized, and its spin-trapping properties were investigated. The rate of
      formation of CPCOMPO-O2H was determined using competition kinetics between the
      superoxide/hydroperoxyl radical (O2*-/HO2*) trapping by CPCOMPO and the
      spontaneous dismutation of this radical in aqueous media. The rate constant of 60
      M-1.s-1 is the highest rate constant thus far observed at neutral pH for any
      nitrones using the kinetic method employed. Decay kinetics were also
      experimentally investigated for CPCOMPO-O2H. The effect of rigid H-bond acceptor
      on the stability of the CPCOMPO-O2H were computationally rationalized and
      compared to that of EMPO-O2H, which has flexible H-bond acceptor, and results
      show the need of a "loose" H-bond acceptor for improved adduct stability.

PMID- 18331055
TI  - 1,3-Dipolar cycloaddition of N-substituted dipolarophiles and nitrones: highly
      efficient solvent-free reaction.
AB  - New isoxazolidines were synthesized in good to excellent yields by 1,3-dipolar
      cycloaddition of N-vinylamide dipolarophiles and nitrones. Strikingly, solvent
      free conditions gave high conversion and yields, shortened reaction time, and
      minimized degradation products. N-Vinyloxazolidin-2-one and its analogues used in
      these cycloaddition reactions were conveniently prepared in excellent yields by a
      modified version of Buchwald's one-step copper-catalyzed vinylation using vinyl
      bromide. From the adducts, a two-step access to various unsymmetric aspartate
      derivatives was also described.

PMID- 18331056
TI  - Zinc-catalyzed silylation of terminal alkynes.
AB  - A rapid and high-yielding silylation of terminal alkynes employing TMSOTf and
      catalytic quantities of Zn(OTf)2 has been developed. The reaction works well for
      a variety of substrates including reactive esters. Fifteen examples with yields
      of >90% are reported.

PMID- 18331057
TI  - Expanding the registry of aromatic amide foldamers: folding, photochemistry and
      assembly using diaza-anthracene units.
AB  - The synthesis of various 1,8-diaza-4,5-dialkoxy-2,7-anthracene dicarboxylic acid
      derivatives and their incorporation into cyclic and helically folded aromatic
      oligoamides are reported. The ability of the diaza-anthracene monomers to undergo
      photoaddition or head-to-tail photodimerization was investigated in the solid
      state and in solution. Quantitative conversion of a monomer diester to the
      corresponding head-to-tail photodimer could be achieved in the solid state
      without protection from oxygen. The formation of an emissive excimer between two
      diaza-anthracene units appended at the end of a helically folded oligomer was
      demonstrated. Intramolecular photodimerization was not observed in this compound,
      possibly due to the low thermal stability of the head-to-head photoadduct. A
      cyclic oligoamide composed of two diaza-anthracene and two pyridine units was
      shown to adopt a flat conformation and to form columnar stacks in the solid
      state. Longer, noncyclic oligoamides composed of one or two diaza-anthracene
      units were shown to adopt helical conformations that exist preferentially as
      double helical dimers.

PMID- 18331058
TI  - A new series of N-[2,4-dioxo-6-d-ribitylamino-1,2,3,4-tetrahydropyrimidin-5
      yl]oxalamic acid derivatives as inhibitors of lumazine synthase and riboflavin
      synthase: design, synthesis, biochemical evaluation, crystallography, and
      mechanistic implications.
AB  - The penultimate step in the biosynthesis of riboflavin is catalyzed by lumazine
      synthase. Three metabolically stable analogues of the hypothetical intermediate
      proposed to arise after phosphate elimination in the lumazine synthase-catalyzed
      reaction were synthesized and evaluated as lumazine synthase inhibitors. All
      three intermediate analogues were inhibitors of Mycobacterium tuberculosis
      lumazine synthase, Bacillus subtilis lumazine synthase, and Schizosaccharomyces
      pombe lumazine synthase, while one of them proved to be an extremely potent
      inhibitor of Escherichia coli riboflavin synthase with a Ki of 1.3 nM. The
      crystal structure of M. tuberculosis lumazine synthase in complex with one of the
      inhibitors provides a model of the conformation of the intermediate occurring
      immediately after phosphate elimination, supporting a mechanism in which
      phosphate elimination occurs before a conformational change of the Schiff base
      intermediate toward a cyclic structure.

PMID- 18331059
TI  - Mono-, bis-, and tris(crown ether)s assembled around 1,3,5-triaroylbenzene
      scaffolds.
AB  - A concise and experimentally straightforward method for assembling multiple
      benzo(crown ether) units around 1,3,5-triaroylbenzene scaffolds has been
      developed. Symmetrical tris(crown ether)s possessing three benzo(15-crown-5) or
      three benzo(18-crown-6) peripheral substituents have been prepared in good yield
      via cyclotrimerization of monomeric enaminones. Efficient cross
      cyclotrimerizations have also been demonstrated through construction of
      unsymmetrical triaroylbenzenes functionalized with only one or two benzo(15-crown
      5) moieties. The alkali cation-binding abilities of these mono- and polytopic
      crown ethers have been probed through picrate extraction experiments and
      isothermal titration calorimetry. Thermodynamic binding parameters uncovered
      using the latter technique reveal increasing K+/Na+ selectivity in the benzo(15
      crown-5) series of compounds as a function of increasing numbers of benzo(crown)
      units. The data also indicate that the triaroylbenzene-derived bis- and tris
      crown ethers do not engage in intramolecular chelation of cations too large to be
      accommodated by individual crown macrorings. Instead, cation/triaroylbenzene
      stoichiometries and binding profiles indicate formation of alkali metal-bridged
      dimers.

PMID- 18331060
TI  - Modulation of pyrene fluorescence in DNA probes depends upon the nature of the
      conformationally restricted nucleotide.
AB  - The DNA probes (ODNs) containing a 2'-N-(pyren-1-yl)-group on the
      conformationally locked nucleosides [2'-N-(pyren-1-yl)carbonyl-azetidine
      thymidine, Aze-pyr (X), and 2'-N-(pyren-1-yl)carbonyl-aza-ENA thymidine, Aza-ENA
      pyr (Y)], show that they can bind to complementary RNA more strongly than to the
      DNA. The Aze-pyr (X) containing ODNs with the complementary DNA and RNA duplexes
      showed an increase in the fluorescence intensity (measured at lambda em
      approximately 376 nm) depending upon the nearest neighbor at the 3'-end to X [dA
      ( approximately 12-20-fold) > dG ( approximately 9-20-fold) > dT ( approximately
      2.5-20-fold) > dC ( approximately 6-13-fold)]. They give high fluorescence
      quantum yields (Phi F = 0.13-0.89) as compared to those of the single-stranded
      ODNs. The Aza-ENA-pyr (Y)-modified ODNs, on the other hand, showed an enhancement
      of the fluorescence intensity only with the complementary DNA (1.4-3.9-fold, Phi
      F = 0.16-0.47); a very small increase in fluorescence is also observed with the
      complementary RNA (1.1-1.7-fold, Phi F = 0.17-0.22), depending both upon the site
      of the Y modification introduced as well as on the chemical nature of the
      nucleobase adjacent to the modification site into the ODN. The fluorescence
      properties, thermal denaturation experiments, absorption, and circular dichroism
      (CD) studies with the X- and Y-modified ODNs in the form of matched homo- and
      heteroduplexes consistently suggested (i) that the orientation of the pyrene
      moiety is outside the helix of the nucleic acid duplexes containing a dT-d/rA
      base pair at the 3'-end of the modification site for both X and Y types of
      modifications, and (ii) that the microenvironment around the pyrene moiety in the
      ODN/DNA and ODN/RNA duplexes is dictated by the chemical nature of the
      conformational constraint in the sugar moiety, as well as by the nature of
      neighboring nucleobases. The pyrene fluorescence emission in both X and Y types
      of the conformationally restricted nucleotides is found to be sensitive to a
      mismatched base present in the target RNA: (i) The X-modified ODN showed a
      decrease ( approximately 37-fold) in the fluorescence intensity (measured at
      lambda em approximately 376 nm) upon duplex formation with RNA containing a G
      nucleobase mismatch (dT-rG pair instead of dT-rA) opposite to the modification
      site. (ii) In contrast, the Y-modified ODN in the heteroduplex resulted in a
      approximately 3-fold increase in the fluorescence intensity upon dT-rG mismatch,
      instead of matched dT-rA pair, in the RNA strand. Our data corroborate that the
      pyrene moiety is intercalated in the X-modified mismatched ODN/RNA (G mismatch)
      heteroduplex as compared to that of the Y-modified ODN/RNA (G mismatch)
      heteroduplex, in which it is located outside the helix.

PMID- 18331061
TI  - Facile assembly of fused benzo[4,5]furo heterocycles.
AB  - A concise synthesis of fused benzo[4,5]furo heterocycles 18 has been developed.
      Chemo/regioselective Suzuki coupling between 1,2-dihaloarene 17 and alpha
      hydroxyphenylboronic acid or ester 20 gives biaryl phenol 19, which then
      undergoes copper(I) thiophene-2-carboxylate (CuTC)-mediated intramolecular
      cyclization to afford 18 in good overall yield. This method has broad substrate
      scope and allows facile assembly of a wide variety of benzo[4,5]furo
      heterocycles.

PMID- 18331062
TI  - Direct oxidative amidation of aldehydes with anilines under mechanical milling
      conditions.
AB  - Oxone is found to be an effective oxidant for the oxidative amidation of
      aldehydes with anilines to furnish amides in a one-pot process under mechanical
      milling conditions.

PMID- 18331063
TI  - Concise asymmetric synthesis of (+)-CP-99,994 and (+)-L-733,060 via efficient
      construction of homochiral syn-1,2-diamines and syn-1,2-amino alcohols.
AB  - An efficient asymmetric synthesis of human NK-1 SP receptor antagonists (+)-CP
      99,994 and (+)-L-733,060 was achieved starting from a common chiral intermediate
      (5). Our route featured the SmI2-induced reductive coupling of N-tert
      butanesulfinyl imine (7) with aldehyde (6) as the key step as well as pivotal
      transformations of the anti-1,2-amino alcohol thus obtained to homochiral syn-1,2
      amino alcohol and syn-1,2-diamine for the asymmetric synthesis of 2,3
      disubstituted piperidines.

PMID- 18331064
TI  - Global metabolic profiling of Escherichia coli cultures: an evaluation of methods
      for quenching and extraction of intracellular metabolites.
AB  - Metabolomics and systems biology require the acquisition of reproducible, robust,
      reliable, and homogeneous biological data sets. Therefore, we developed and
      validated standard operating procedures (SOPs) for quenching and efficient
      extraction of metabolites from Escherichia coli to determine the best methods to
      approach global analysis of the metabolome. E. coli was grown in chemostat
      culture so that cellular metabolism could be held in reproducible, steady-state
      conditions under a range of precisely defined growth conditions, thus enabling
      sufficient replication of samples. The metabolome profiles were generated using
      gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS). We employed
      univariate and multivariate statistical analyses to determine the most suitable
      method. This investigation indicates that 60% cold (-48 degrees C) methanol
      solution is the most appropriate method to quench metabolism, and we recommend
      100% methanol, also at -48 degrees C, with multiple freeze-thaw cycles for the
      extraction of metabolites. However, complementary extractions would be necessary
      for coverage of the entire complement of metabolites as detected by GC/TOF-MS.
      Finally, the observation that metabolite leakage was significant and measurable
      whichever quenching method is used indicates that methods should be incorporated
      into the experiment to facilitate the accurate quantification of intracellular
      metabolites.

PMID- 18331065
TI  - Shape changes during the drying of droplets of suspensions.
AB  - During drying of droplets of suspensions, several flow regimes contribute to the
      radial flow of powder to the periphery to leave a pile-up of powder at the rim.
      It is shown that the shape of the droplet residues can be controlled both by
      restricting evaporation and by combining high and low boiling point solvents
      which modify particle flows and produce a range of droplet residues varying from
      a concave "doughnut" shape, sometimes with a central hole, to a convex dome
      shape. Addition of formamide to aqueous suspensions is shown to affect powder
      deposition by setting up a Marangoni flow rather than by reducing evaporation at
      the periphery. The results find direct application in thick-film combinatorial
      printing of ceramics to form small disks by droplet drying.

PMID- 18331066
TI  - Tunable wettability of polyimide films based on electrostatic self-assembly of
      ionic liquids.
AB  - We have demonstrated that the surface wettability of negatively charged polyimide
      films could be tuned by electrostatic self-assembly of ionic liquids. The water
      contact angles of the polyimide films varied in the range 27-80 degrees for 13
      different ionic liquids based on imidazolium and ammonium salts. The surface
      morphology of the resulting surfaces was characterized using atomic force
      microscopy. The results revealed that the assembly of longer-substituent cations
      was characterized by the formation of spherical nanoparticles that were formed
      due to sequent aggregation of cations on those electrostatically assembled ones
      via hydrophobic interaction. In this case, the counteranions are present in the
      assembled layers and the wettability is accordingly affected. Whereas for shorter
      substituent cations, no aggregates were formed due to the less hydrophobic
      interaction than the electrostatic repulsive interaction between the cations, and
      the counteranions were absent from the assembled layers. This method can also be
      utilized to quantify the hydrophobicity of various ionic liquids.

PMID- 18331067
TI  - TiO2 band shift by nitrogen-containing heterocycles in dye-sensitized solar
      cells: a periodic density functional theory study.
AB  - A density functional theory (DFT) method (periodic DMol3) with full geometry
      optimization was used to study the adsorption of nitrogen-containing heterocycles
      such as pyrazole, imidazole, 1,2,4-triazole, pyridine, pyrimidine, pyrazine, and
      4-t-butylpyridine (TBP) on TiO2 anatase (101), (100), and (001) surfaces. All
      structures displayed a negative shift in the TiO2 Fermi level upon adsorption of
      N-containing heterocycles. Additionally, the heterocycles were examined as an
      additive in an I-/I3- redox electrolyte solution of dye-sensitized TiO2 solar
      cell. The DFT results indicated that the negative shift of TiO2 Fermi level was
      due to the adsorbate dipole moment component normal to the TiO2 surface plane,
      and corresponded to the enhanced open-circuit photovoltage (Voc) and the reduced
      short-circuit photocurrent density (Jsc) in a dye-sensitized solar cell.

PMID- 18331068
TI  - Self-assembly of pluronic block copolymers in aqueous dispersions of single-wall
      carbon nanotubes as observed by spin probe EPR.
AB  - The self-assembly of Pluronic block copolymers in dispersions of single-wall
      carbon nanotubes (SWNT) was investigated by spin probe electron paramagnetic
      resonance (EPR) spectroscopy. Nitroxide spin labeled block copolymers derived
      from Pluronic L62 and P123 were introduced in minute amounts into the
      dispersions. X-band EPR spectra of the SWNT dispersions and of native polymer
      solutions were measured as a function of temperature. All spectra, below and
      above the critical micelle temperature (CMT), were characteristic of the fast
      limit motional regime. The temperature dependence of the 14N isotropic hyperfine
      coupling, aiso, and the rotational correlation time, tauc, were determined. It
      was observed that, below the CMT, EPR does not distinguish between chains
      adsorbed on SWNT and free chains. Above CMT, substantial differences were
      observed: in the native solution, the Pluronics spin labels experience only one
      environment, Sm, assigned to spin labels in the corona of the Pluronic micelle,
      whereas in the SWNT dispersions, in addition to Sm, a second population of
      nonaggregated, individual chains, Si, is observed. The relative amounts of Sm and
      Si were found to depend on the relative concentrations of the Pluronic and SWNT.
      Furthermore, the aggregates formed in the SWNT dispersions do not show the
      typical increase in chain-end mobility as a function of temperature, observed in
      the post-CMT regime of the native Pluronic solutions. This suggests a larger
      dynamical coupling among aggregated chains in the presence of the SWNT as
      compared to the native micelles. The overall findings are consistent with the
      formation of a new type of aggregates, composed of a SWNT-polymer hybrid.

PMID- 18331069
TI  - Dynamics of bubble formation in highly viscous liquids.
AB  - There has recently been considerable interest in the development of devices for
      the preparation of monodisperse microbubble suspensions for use as ultrasound
      contrast agents and drug delivery vehicles. These applications require not only a
      high degree of bubble uniformity but also a maximum bubble size of 8 mum, and
      this provides a strong motivation for developing an improved understanding of the
      process of bubble formation in a given device. The aim of this work was to
      investigate bubble formation in a T-junction device and determine the influence
      of the different processing parameters upon bubble size, in particular, liquid
      viscosity. Images of air bubble formation in a specially designed T-junction were
      recorded using a high-speed camera for different ratios of liquid to gas flow
      rate (Ql/Qg) and different liquid viscosities (microl). It was found that
      theoretical predictions of the flow profile in the focal region based on analysis
      of axisymmetric Stokes flow were accurate to within 6% when compared with the
      experimental data, indicating that this provided a suitable means of describing
      the bubble formation process. Both the theoretical and experimental results
      showed that Ql/Qg and mul had a significant influence upon bubble formation and
      eventual size, with higher flow rates and higher viscosities producing smaller
      bubbles. There were, however, found to be limiting values of Ql/Qg and mul beyond
      which no further reduction in bubble size was achieved.

PMID- 18331070
TI  - Influenza vaccination and the elderly: pandemic preparedness.
AB  - Seasonal influenza causes significant morbidity and mortality in the elderly, the
      very young and those with chronic illness, despite the availability of effective
      vaccines. The mortality and morbidity attributed annually to seasonal influenza
      are small in comparison to the potential mortality and morbidity of a novel
      highly pathogenic human influenza A virus strain. The current influenza A/H5N1
      virus that has caused epidemics in poultry and is evolving to find new niches
      needs only to become more efficiently transmitted from human to human to cause
      the next pandemic. Vaccination is the intervention with the potential to save the
      most lives when a pandemic occurs. Pandemic awareness and preparedness are
      essential to decrease the predicted chaos, death and illness arising from the
      next influenza pandemic.

PMID- 18331071
TI  - Use of gabapentin in the treatment of behavioural and psychological symptoms of
      dementia: a review of the evidence.
AB  - Behavioural and psychological symptoms of dementia (BPSD) have been defined as a
      heterogeneous range of psychological reactions, psychiatric symptoms and
      behaviours that may be unsafe, disruptive and impair the care of a patient in a
      given environment. To date, there are no US FDA-approved drugs or clear standards
      of pharmacological care for the treatment of BPSD. The novel antiepileptic agent
      gabapentin is being increasingly considered for use in the geriatric population
      because of its relatively favourable safety profile compared with other classes
      of psychiatric medications. Gabapentin has been administered to several geriatric
      patients with bipolar disorder and patients with dementia. It has also been
      reported to be successful in the treatment of a 13-year-old boy with behavioural
      dyscontrol, a finding that suggested a possible role for gabapentin in the
      treatment of other behavioural disorders. The purpose of this review was to find
      evidence for the use of gabapentin in the treatment of BPSD. To this end, a
      search was performed for case reports, case series, controlled trials and reviews
      of gabapentin in the treatment of this condition. The key words 'dementia',
      'Alzheimer's disease' and 'gabapentin' were used. Searches were performed in
      PubMed, PsycINFO, Ovid MEDLINE, Cochrane Library and ClinicalTrials.gov. The
      search revealed that there are limited data on the efficacy of gabapentin for
      BPSD in the form of 11 case reports, 3 case series and 1 retrospective chart
      review; no controlled studies appear to have been published to date on this
      topic. In most of the reviewed cases, gabapentin was reported to be a well
      tolerated and effective treatment for BPSD. However, two case reports in which
      gabapentin was used in the context of agitation in dementia with Lewy bodies
      questioned the appropriateness of gabapentin for all types of dementia-related
      agitation. The dearth of available data limits support for the off-label use of
      gabapentin for the treatment of BPSD. Furthermore, controlled studies should be
      conducted before gabapentin can be clinically indicated for the successful
      treatment of BPSD.

PMID- 18331073
TI  - Resectable non-small cell lung cancer in the elderly: is there a role for
      adjuvant treatment?
AB  - Over the past 2 years, systemic chemotherapy has emerged as the standard adjuvant
      approach for resectable non-small cell lung cancer (NSCLC). In aggregate, a 5.3%
      improvement in 5-year survival has been observed with platinum-based combination
      chemotherapy in patients with NSCLC, with benefits being most pronounced in stage
      II and IIIa disease. Recent data suggest that the elderly (up to age 75 years)
      derive benefits from such therapy similar to those seen in younger patients.
      Unfortunately, although patients aged >or=70 years constitute 50% of those with
      newly diagnosed NSCLC, <10% of enrollees in clinical trials are in this age
      group. To help offset the spectre of increased risk in this age group, two
      potential strategies exist: (i) substitution of carboplatin for cisplatin; and
      (ii) increased use of neoadjuvant treatment to avoid perioperative co-morbidities
      and difficulties with compliance that can hamper appropriate administration of
      adjuvant treatment. To date, there have been no elderly-specific adjuvant trials
      in NSCLC. Over time, this omission is likely to be corrected.

PMID- 18331072
TI  - Clinical efficacy of esomeprazole in the prevention and healing of
      gastrointestinal toxicity associated with NSAIDs in elderly patients.
AB  - NSAIDs are widely prescribed for the treatment of pain, inflammation and
      rheumatic disorders, but their use is associated with adverse gastrointestinal
      effects, ranging from dyspeptic symptoms and peptic ulcers to more serious
      complications. Elderly patients are at high risk of experiencing NSAID-induced
      gastrointestinal tract injury and should be considered candidates for
      prophylactic pharmacological therapy. In studies conducted in adult patients,
      proton pump inhibitors (PPIs) such as esomeprazole have been shown to prevent or
      reduce NSAID-induced gastrointestinal injury. The beneficial effects of
      esomeprazole can be ascribed largely to its ability to maintain sustained
      inhibition of gastric acid secretion, although there is evidence to suggest that
      pharmacodynamic properties unrelated to acid inhibition may also contribute to
      the gastroprotective effects of this agent. Although there are limited data on
      the use of esomeprazole specifically in elderly patient populations, studies of
      patients at high risk of NSAID-induced gastrointestinal toxicity because of
      advanced age indicate that this PPI is both effective and well tolerated when
      administered in conjunction with NSAIDs. Thus, esomeprazole can be regarded as a
      useful option for prophylactic therapy in elderly patients receiving long-term
      NSAID therapy.

PMID- 18331074
TI  - Clinical features, differential diagnosis and treatment of autoimmune hepatitis
      in the elderly.
AB  - Autoimmune hepatitis affects all ages, and it is probably under-diagnosed in the
      elderly. Patients aged >or= 60 years have a higher frequency of cirrhosis at
      presentation than adults aged <or= 30 years, and they more commonly have HLA
      DRB1*04. These findings suggest that host factors affect the clinical phenotype
      by influencing the antigens that are presented to immunocytes and the nature of
      the immune response. The elderly may have an indolent progressive disease that is
      asymptomatic or masked by other concurrent rheumatic conditions. An acute, even
      fulminant, presentation may reflect de novo disease or a spontaneous exacerbation
      of a pre-existent chronic process. Centrilobular (zone 3) necrosis may reflect an
      early histological stage that transforms later to classical interface hepatitis.
      Diagnostic criteria have been codified, and a scoring system allows systemic
      assessment of all clinical features and quantifies the strength of the diagnosis.
      Prednisone in combination with azathioprine is the safest effective initial
      treatment, and all elderly patients with severe disease should be treated
      vigorously to full resolution of clinical, laboratory and histological features.
      Adverse effects of treatment occur mainly with protracted treatment (>18 months)
      and repeated therapies after relapse. Adjustments in the management strategy are
      warranted for an incomplete response or a need for re-treatment after relapse.
      Azathioprine (2 mg/kg/day) should be used as a corticosteroid-sparing, long-term
      maintenance therapy in these instances. Treatment failure is uncommon in the
      elderly, and age-related changes in the cellular immune response may attenuate
      the disease and enhance its response to therapy. Concurrent adjuvant therapies
      must focus on maintenance of bone density.

PMID- 18331075
TI  - Cardiovascular implications of chronic kidney disease in older adults.
AB  - Because serum creatinine is an imprecise indicator of glomerular filtration rate
      (GFR), estimating equations derived from the Modification of Diet in Renal
      Diseases study are increasingly being used to estimate GFR. The notion that GFR
      declines with aging is based largely on the results of cross-sectional studies
      that have generally not differentiated the effects of senescence from those of co
      existing conditions such as hypertension. Nevertheless, GFR probably declines in
      many, if not all, aging individuals. The introduction of automated reporting of
      estimated GFR may result in an over-diagnosis of chronic kidney disease (CKD).
      There is a large body of evidence to suggest that a decrease in GFR and/or
      albuminuria is associated with an increased risk of death, particularly from
      cardiovascular causes, and that this risk extends to the elderly. Although the
      data are not consistent with regard to the level of GFR at which the increase in
      cardiovascular risk becomes apparent, small amounts of urine albumin excretion
      (levels that do not meet the definition of microalbuminuria) are associated with
      a higher risk of death, even among the elderly. There is currently no evidence
      that aggressive control of blood pressure and/or use of medications that reduce
      proteinuria, such as those that block the renin-angiotensin-aldosterone system,
      reduce the risk of cardiovascular events or death among individuals with CKD. On
      the other hand, secondary analyses of at least two studies have documented the
      benefit of lipid lowering in CKD patients. Paradoxically, a recent study has
      raised concern that normalizing haemoglobin may enhance the cardiovascular risk
      associated with CKD. To conclude, the available evidence indicates that early
      identification of CKD may allow physicians to aggressively modify cardiovascular
      risk, which, in turn, has the potential to improve patient outcomes.

PMID- 18331077
TI  - A combined theoretical treatment of T(1)-->S(0) intersystem crossing and
      intramolecular vibrational redistribution in thiophosgene.
AB  - We combine our two recent theoretical approaches for electronic relaxation T(1)-
      >S(0) and vibrational relaxation processes in thiophosgene (SCCl(2)) to provide a
      more detailed picture of the intersystem crossing (ISC) and phosphorescence from
      the first triplet T(1). Our analysis shows that ISC is not a true irreversible
      decay and should lead to violent phosphorescence quantum beats that could be
      observed experimentally.

PMID- 18331076
TI  - Association between visual acuity and medical and non-medical costs in patients
      with wet age-related macular degeneration in France, Germany and Italy.
AB  - INTRODUCTION: Exudative ('wet') age-related macular degeneration (ARMD) is the
      major cause of blindness in Western developed countries. Treatments aimed at
      preserving vision are already available and new compounds are under development.
      Micro-economics information will be pivotal to justifying forthcoming investment.
      OBJECTIVE: This study sought to investigate the costs of exudative ARMD in
      patients who were actively treated at ophthalmology referral centres in three
      European countries: France, Germany and Italy. METHOD: This cross-sectional
      observational study was conducted in France, Germany and Italy in 2004. The
      following data were collected: ARMD description, visual acuity (VA), and the
      medical and non-medical resources used for ARMD in the preceding year. The
      economic perspective was that of society. ANOVA for cost variables estimated the
      impact of ARMD per eye, adjusted for sex and age. Both hospital and ambulatory
      eye centres were included. Patients with exudative ARMD were stratified into four
      levels of severity using VA thresholds of 20/200 for the worst eye (WE) and 20/40
      for the best eye (BE). The main outcome measure was medical and non-medical
      costs. RESULTS: 360 patients were included (females 60%; mean age 77 years; mean
      interval since diagnosis 2.3 years). The two groups with the greatest difference
      in severity of VA loss consisted of BE >or= 20/40, WE >or= 20/200 (27.2% of
      patients) and BE <20/40, WE <20/200 (25.5% of patients). Total cost was two
      thirds medical and one-third non-medical. Total costs increased with ARMD
      severity and were 1.1-2 times greater for severe disease compared with less
      severe disease. Average medical costs (2004 values) in France were euro 3714,
      compared with euro 1810 in Germany and euro 2020 in Italy, and showed slight
      increases with ARMD severity. Non-medical costs were significantly higher for
      patients with severe disease and highest in Germany. CONCLUSION: The impact of
      ARMD on costs was considerable and a positive correlation was found between total
      costs and ARMD severity. Differences among countries were partly explained by
      differences in customary care delivery.

PMID- 18331078
TI  - Negative electron binding energies observed in a triply charged anion:
      photoelectron spectroscopy of 1-hydroxy-3,6,8-pyrene-trisulfonate.
AB  - We report the observation of negative electron binding energies (BEs) in a triply
      charged anion, 1-hydroxy-3,6,8-pyrene-trisulfonate (HPTS(3-)). Low-temperature
      photoelectron spectra were obtained for HPTS(3-) at several photon energies,
      revealing three detachment features below 0 electron BE. The HPTS(3-) trianion
      was measured to possess a negative BE of -0.66 eV. Despite the relatively high
      excess energy stored in HPTS(3-), it was observed to be a long-lived anion due to
      its high repulsive Coulomb barrier (RCB) ( approximately 3.3 eV), which prevents
      spontaneous electron emission. Theoretical calculations were carried out, which
      confirmed the negative electron BEs observed. The calculations further showed
      that the highest occupied molecular orbital in HPTS(3-) is an antibonding pi
      orbital on the pyrene rings, followed by lone pair electrons in the peripheral 
      SO(3) (-) groups. Negative electron BE is a unique feature of multiply charged
      anions due to the presence of the RCB. Such metastable species may be good models
      to study electron-electron and vibronic interactions in complex molecules.

PMID- 18331079
TI  - Full six-dimensional nonadiabatic quantum dynamics calculation for the energy
      pooling reaction O(2)(a (1)Delta)+O(2)(a (1)Delta)-->O(2)(b (1)Sigma)+O(2)(X
      (3)Sigma).
AB  - Six new potential energy surfaces of four singlet states and two triplet states
      for the title oxygen molecule reaction along with the spin-orbit coupling among
      them have been constructed from the complete active space second-order
      perturbation theory with a 6-311+G(d) basis. Accurate integral cross sections are
      calculated with a full six-dimensional nonadiabatic time-dependent quantum wave
      packet method. The thermal rate constant based on the integral cross sections
      agrees well with the result of the experimental measurements, and the intersystem
      crossing effects are also discussed in this electronic energy-transfer process.

PMID- 18331080
TI  - Photostability of electronically excited polyacenes: a case study of vibronic
      coupling in the naphthalene radical cation.
AB  - Novel issues of electronic nonadiabatic coupling in the excited state dynamics of
      prototypical naphthalene radical cation of polycyclic aromatic hydrocarbon of the
      polyacene family are theoretically investigated. A benchmark ab initio quantum
      dynamical study is performed and its complex vibronic spectra and nonradiative
      decay are examined. The findings are in very good accord with the experiment,
      unambiguously establishing the crucial role of intricate electron-nuclear
      coupling in the photoinduced dynamical processes of this system.

PMID- 18331081
TI  - Molecular orbital propagation to accelerate self-consistent-field convergence in
      an ab initio molecular dynamics simulation.
AB  - Based on the idea of molecular orbital (MO) propagation, we propose a novel
      effective method for predicting initial guesses for the self-consistent-field
      calculations in direct ab initio molecular dynamics (AIMD) simulations. This
      method, called LIMO, adopts the Lagrange interpolation (LI) polynomial technique
      and predicts initial MO coefficients at the next AIMD step by using several
      previous results. Taking into account the crossing and/or mixing of MOs leads to
      orbital invariant formulas for the LIMO method. We also propose a simple method
      for determining the optimal degree of the LI polynomial, which corresponds to the
      number of previous steps. Numerical tests confirm that this proposed method is
      both effective and feasible.

PMID- 18331082
TI  - Barrier scattering with complex-valued quantum trajectories: taxonomy and
      analysis of isochrones.
AB  - To facilitate the search for isochrones when using complex-valued trajectory
      methods for quantum barrier scattering calculations, the structure and shape of
      isochrones in the complex plane were studied. Isochrone segments were categorized
      based on their distinguishing features, which are shared by each situation
      studied: High and low energy wave packets, scattering from both thick and thin
      Gaussian and Eckart barriers of varying height. The characteristic shape of the
      isochrone is a trifurcated system: Trajectories that transmit the barrier are
      launched from the lower branch (T), while the middle and upper branches form the
      segments for reflected trajectories (F and B). In addition, a model is presented
      for the curved section of the lower branch (from which transmitted trajectories
      are launched), and important features of the complex extension of the initial
      wave packet are identified.

PMID- 18331083
TI  - Complex polarization propagator calculations of magnetic circular dichroism
      spectra.
AB  - It is demonstrated that the employment of the nonlinear complex polarization
      propagator enables the calculation of the complete magnetic circular dichroism
      spectra of closed-shell molecules, including at the same time both the so-called
      Faraday A and B terms. In this approach, the differential absorption of right and
      left circularly polarized light in the presence of a static magnetic field is
      determined from the real part of the magnetic field-perturbed electric dipole
      polarizability. The introduction of the finite lifetimes of the electronically
      excited states into the theory results in response functions that are well
      behaved in the entire spectral region, i.e., the divergencies that are found in
      conventional response theory approaches at the transition energies of the system
      are not present. The applicability of the approach is demonstrated by
      calculations of the ultraviolet magnetic circular dichroism spectra of para
      benzoquinone, tetrachloro-para-benzoquinone, and cyclopropane. The present
      results are obtained with the complex polarization propagator approach in
      conjunction with Kohn-Sham density functional theory and the standard adiabatic
      density functionals B3LYP, CAM-B3LYP, and BHLYP.

PMID- 18331084
TI  - Global uniform semiclassical approximation for Clebsch-Gordan coefficients.
AB  - Semiclassical integral representations, analogous to initial value expressions
      for the propagator, are presented for the Clebsch-Gordan angular momentum
      coupling coefficients. Two forms (L and R types) of the approximation are
      presented. For each form, new non-Gaussian expressions, which are specifically
      adapted to the nature of angular momentum variables, are proposed in place of the
      familiar Gaussian coherent state functions. With these non-Gaussian kernels, it
      is found that the present treatments are capable of accuracy similar to that
      obtained from a uniform Airy approximation. Although the present semiclassical
      approximations involve only real-valued angle variables, associated with sets of
      angular momenta that are related by ordinary, real, classical transformations,
      the treatments produce accurate results not only for classically allowed choices
      of quantum numbers but also for very strongly classically forbidden values.

PMID- 18331085
TI  - Formulation and implementation of direct algorithm for the symmetry-adapted
      cluster and symmetry-adapted cluster-configuration interaction method.
AB  - We present a new computational algorithm, called direct algorithm, for the
      symmetry-adapted cluster (SAC) and SAC-configuration interaction (SAC-CI)
      methodology for the ground, excited, ionized, and electron-attached states. The
      perturbation-selection technique and the molecular orbital index based direct
      sigma-vector algorithm were combined efficiently with the use of the sparse
      nature of the matrices involved. The formal computational cost was reduced to
      O(N(2)xM) for a system with N-active orbitals and M-selected excitation
      operators. The new direct SAC-CI program has been applied to several small
      molecules and free-base porphin and has been shown to be more efficient than the
      conventional nondirect SAC-CI program for almost all cases. Particularly, the
      acceleration was significant for large dimensional computations. The direct SAC
      CI algorithm has achieved an improvement in both accuracy and efficiency. It
      would open a new possibility in the SAC/SAC-CI methodology for studying various
      kinds of ground, excited, and ionized states of molecules.

PMID- 18331086
TI  - A divide-and-conquer strategy to improve diffusion sampling in generalized
      ensemble simulations.
AB  - Generalized ensemble simulations generally suffer from the associated diffusion
      sampling problem; the increased entropic barrier can greatly abolish sampling
      efficiency, in particular, with the increase of number of degrees of freedom in
      the target conformational space. Taking advantage of the recent simulated scaling
      method, we formulate a divide-and-conquer sampling strategy to solve this problem
      so as to robustly improve the sampling efficiency in generalized ensemble
      simulations. In the present method, the target conformational space sampling
      enhancement is decomposed to the sampling enhancements of several
      subconformational regions, and multiple independent SS simulations are performed
      to establish the individual sampling enhancement for each of the
      subconformational regions; in order to realize the global importance sampling,
      structure exchanges among these replicas are performed based on the Monte Carlo
      acceptance/rejection procedure. As demonstrated in our studies, the present
      divide-and-conquer sampling algorithm, named by us as "simulated scaling based
      variant Hamiltonian replica exchange method," has superior sampling capability so
      as to possibly play an essential role in dealing with the present bottleneck of
      generalized ensemble method developments: the system size limitations.

PMID- 18331087
TI  - Quadrupolelike electrostatic guiding for cold polar molecules.
AB  - We demonstrate electrostatic guiding of cold heavy water (D(2)O) molecules over a
      distance of 44.5 cm by using a quadrupolelike electrostatic field, which is
      generated by the combination of two parallel charged poles and two grounded metal
      plates. We measure the transverse spatial distribution of the guided D(2)O
      molecular beam and study the dependence of the relative guiding efficiency and
      the transverse temperature of the guided molecular beam on the guiding voltage.
      Our study shows that the maximum guiding efficiency of approximately 50% can be
      obtained, and our experimental results are in good agreement with ones of
      theoretical calculation and Monte Carlo simulations, and this guiding scheme has
      some potential applications in molecule optics, such as molecular-beam splitter,
      integrated molecular optics, etc.

PMID- 18331088
TI  - Terahertz vibration-rotation-tunneling spectroscopy of the water tetramer-d8:
      combined analysis of vibrational bands at 4.1 and 2.0 THz.
AB  - We report the measurement of terahertz vibration-rotation-tunneling spectra of
      (D(2)O)(4) in the spectral region near 4.13 THz. The characterization of this
      perpendicular band extends a previously reported study [J. Chem. Phys. 111, 7801
      (1999)]. We observed 239 new transitions, each being split into a doublet of
      constant (approximately 192 MHz) spacing. These are included in a combined fit
      with the 113 previously measured transitions of the 2.03 THz parallel band using
      an effective Hamiltonian similar to that used in the global fit of the water
      trimer. The detailed understanding of the water tetramer evolving from this work
      underlies our efforts to quantify the contribution of many-body forces to the
      hydrogen bonding interactions in condensed phase water.

PMID- 18331089
TI  - Lineshape of rotational spectrum of CO in (4)He droplets.
AB  - In a recent experiment the rovibrational spectrum of CO isotopomers in superfluid
      helium-4 droplets was measured, and a Lorentzian lineshape with a large line
      width of 0.024 K (half width at half maximum) was observed [von Haeften et al.,
      Phys. Rev. B 73, 054502 (2006)]. In the accompanying theoretical analysis it was
      concluded that the broadening mechanism may be homogeneous and due to coupling to
      collective droplet excitations (phonons). Here we generalize the lineshape
      analysis to account for the statistical distribution of droplet sizes present in
      nozzle expansion experiments. These calculations suggest an alternative
      explanation for the spectral broadening, namely, that the coupling to phonons can
      give rise to an inhomogeneous broadening as a result of averaging isolated
      rotation-phonon resonances over a broad cluster size distribution. This is seen
      to result in Lorentzian lineshapes, with a width and peak position that depend
      weakly on the size distribution, showing oscillatory behavior for the narrower
      size distributions. These oscillations decrease with droplet size and for large
      enough droplets ( approximately 10(4)) the line widths saturate at a value equal
      to the homogeneous line width calculated for the bulk limit.

PMID- 18331090
TI  - Equilibrium properties of quantum water clusters by the variational Gaussian
      wavepacket method.
AB  - The variational Gaussian wavepacket (VGW) method in combination with the replica
      exchange Monte Carlo is applied to calculations of the heat capacities of quantum
      water clusters, (H(2)O)(8) and (H(2)O)(10). The VGW method is most conveniently
      formulated in Cartesian coordinates. These in turn require the use of a flexible
      (i.e., unconstrained) water potential. When the latter is fitted as a linear
      combination of Gaussians, all the terms involved in the numerical solution of the
      VGW equations of motion are analytic. When a flexible water model is used, a
      large difference in the timescales of the inter- and intramolecular degrees of
      freedom generally makes the system very difficult to simulate numerically. Yet,
      given this difficulty, we demonstrate that our methodology is still practical. We
      compare the computed heat capacities to those for the corresponding classical
      systems. As expected, the quantum effects shift the melting temperatures toward
      the lower values.

PMID- 18331091
TI  - Density-functional study of small neutral and cationic bismuth clusters Bi(n) and
      Bi(n) (+)(n=2-24).
AB  - Density-functional theory with scalar-relativistic pseudopotential and a
      generalized gradient correction is used to calculate the neutral and cationic
      Bi(n) clusters (2< or =n< or =24), with the aim to elucidate their structural
      evolution, relative stability, and magnetic property. The structures of neutral
      Bi clusters are found to be similar to that of other group-V elemental clusters,
      with the extensively studied sizes of n=4 and 8 having a tetrahedron and
      wedgelike structure, respectively. Generally, larger Bi clusters consist of a
      combination of several stable units of Bi(4), Bi(6), and Bi(8), and they have a
      tendency to form an amorphous structure with the increase of cluster sizes. The
      curves of second order energy difference exhibit strong odd-even alternations for
      both neutral and cationic Bi clusters, indicating that even-atom (odd-atom) sizes
      are relatively stable in neutral clusters (cationic clusters). The calculated
      magnetic moments are 1micro (B) for odd-atom clusters and zero for even-atom
      clusters. We propose that the difference in magnetism between experiment and
      theory can be greatly improved by considering the orbital contribution. The
      calculated fragmentation behavior agrees well with the experiment, and for each
      cationic cluster the dissociation into Bi(4) or Bi(7) (+) subclusters confirms
      the special stability of Bi(4) and Bi(7) (+). Moreover, the bond orders and the
      gaps between the highest occupied molecular orbital and the lowest unoccupied
      molecular orbital show that small Bi clusters would prefer semiconductor
      characters to metallicity.

PMID- 18331092
TI  - Large-amplitude quantum mechanics in polyatomic hydrides. II. A particle-on-a
      sphere model for XH(n) (n=4,5).
AB  - This paper describes the application of a relatively simple, but computationally
      tractable, "particle-on-a-sphere" (POS) model for quantum-mechanical calculation
      of large-amplitude, H atom dynamics in polyatomic hydrides (XH(n)), based on
      radially relaxed, two-dimensional angular motion of H atoms on the surface of a
      sphere. This work focuses on systems with many degrees of freedom, i.e., XH(4)
      (eight dimensional) and XH(5) (ten dimensional), with corresponding molecular
      analogs of CH(4) and CH(5) (+) and is applicable to rovibrationally excited
      states with J> or =0. A pairwise-additive potential fit for CH(5) (+), which
      yields remarkable agreement with geometries, energies, and barrier heights on the
      full-dimensional surface of Brown et al. [J. Chem. Phys. 121, 4105 (2004)] is
      presented. Comparisons with experimental data and diffusion quantum Monte Carlo
      (DMC) methods test convergence for the POS model and provide insight into
      multidimensional quantum rovibrational dynamics. In particular, POS energy-level
      patterns for a series of scaled CH(5) (+) potentials indicate an absence of
      strong tunneling behavior, consistent with the highly delocalized wave functions,
      large zero-point energies, and small interconversion barriers noted in previous
      DMC studies of Brown et al.

PMID- 18331093
TI  - Electronic structure of oxide, peroxide, and superoxide clusters of the 3d
      elements: a comparative density functional study.
AB  - The 3d-element transition metal dioxide MO(2), peroxide M(O(2)), and superoxide
      MOO clusters (M=Sc-Zn), are studied by density functional theory with the B1LYP
      functional. The reliability of the methods and basis sets employed was tested by
      a reinvestigation of the monoxides, for which a database of experimental data is
      available. The global minima on the M+O(2) potential energy surfaces correspond
      to dioxide structure, the only exception being CuOO, with a superoxide structure.
      All Zn dioxygen clusters are thermodynamically unstable-their ground states lie
      higher than the dissociation limit to Zn+O(2). Our calculations are in favor of
      the high-spin configurations for the FeO(2), CoO(2), and NiO(2) ground states,
      which are still a subject of extensive theoretical and experimental studies.
      These assignments are confirmed by the coupled-cluster method, CCSD(T), except
      for NiO(2). Based on the existence of a stable NiO(2) monoanion in a (4)B(1)
      state, however, it can be concluded that NiO(2) in its (5)A(1) state should also
      be stable. The vibrational frequencies are calculated for clusters entrapped in
      the cubic cell of solid Ar matrix and compared with those obtained for gas-phase
      clusters. The matrix has no influence on the vibrations of the monoxides and most
      of the dioxides; however, Co and Ni-dioxoclusters interact strongly with the
      atoms from the noble gas matrix. The most intense frequencies in the IR spectra
      are shifted to lower energies and the ordering of the low-lying electronic states
      by stability is also reversed. According to the electrostatic potential maps, the
      oxygen atoms in the peroxides are more nucleophilic than those in the dioxides
      and superoxides. The terminal oxygen atom in superoxides is more nucleophilic
      than its M-bonded oxygen atom, though charge distribution analysis predicts a
      smaller negative charge on the terminal oxygen. TiO(2) is the only dioxide in
      which nucleophilic character in the vicinity of the metal cation is induced.

PMID- 18331094
TI  - Interchange-tunneling splitting in HCl dimer in helium nanodroplets.
AB  - Midinfrared spectra of HCl dimers have been obtained in helium nanodroplets. The
      interchange-tunneling (IT) splitting in the vibrationally excited state of the
      bonded H-Cl stretching band (nu(2)) in (H(35)Cl-H(37)Cl) dimers was measured to
      be 2.7+/-0.2 cm(-1), as compared to 3.7 cm(-1) in free dimer. From the splitting,
      the strength of the IT coupling in liquid helium of 0.85+/-0.15 cm(-1) was
      obtained, which is about a factor of 2 smaller than in the free dimer. The
      results are compared with the previous spectroscopic study of (HF)(2) in He
      droplets as well as the theoretical study of (HF)(2) and (HCl)(2) dimers in small
      He clusters.

PMID- 18331095
TI  - Experimental and theoretical investigation of electron attachment to SF(5)Cl.
AB  - Thermal electron attachment to SF(5)Cl has been studied with the flowing
      afterglow Langmuir probe technique. The rate coefficient is moderate, 4.8(+/
      1.2)x10(-8) cm(3) s(-1), and invariant with temperature over the temperature
      range of 300-550 K. The reaction is dissociative, forming mainly SF(5) (-)+Cl.
      Minor yields of Cl(-) and FCl(-) were also found. The yields of the minor
      channels increase slightly with temperature. Statistical unimolecular rate
      modeling is employed to elucidate the character of the dissociation pathways and
      to support the assumption that the dissociations involve the formation of
      metastable anionic SF(5)Cl(-).

PMID- 18331096
TI  - G3 and density functional theory investigations of the structures and energies of
      SF(n)Cl (n=0-5) and their anions.
AB  - Computations of structures and total energies have been carried out for neutral
      and anionic SF(n)Cl (n=0-5), using the composite G3 method and density functional
      theory (DFT) at the B3LYP6-311+G(3df) level. The total energies and zero-point
      energies have been used here to derive electron affinities, bond dissociation
      energies, and heats of formation. In addition, vibrational frequencies,
      polarizabilities, and dipole moments are reported. Results are compared with
      earlier work for SF(m) (m=1-6) and demonstrate how the relatively weak S-Cl bond
      and reduced symmetry influence the properties of these molecules and anions.
      Comparisons are also made between G3 and DFT results for SF(n)Cl. Of particular
      interest is the alternating pattern of agreement between calculated electron
      affinity values with n. These calculations also provide critical energetic data
      needed to understand experimental measurements of electron attachment to SF(5)Cl
      [Van Doren et al., J. Chem. Phys. 128, 094309 (2008)] for which numerous ion
      products have been reported in the literature at low electron energy.

PMID- 18331097
TI  - Rovibrationally selected and resolved pulsed field ionization-photoelectron study
      of propyne: ionization energy and spin-orbit interaction in propyne cation.
AB  - By using a high-resolution infrared (IR) laser to prepare propyne (C(3)H(4)) in
      selected rotational levels of the excited nu(1) (acetylenic C-H stretching)
      vibration mode prior to vacuum ultraviolet (VUV) laser pulsed field ionization
      photoelectron (PFI-PE) measurements, we have obtained rotationally resolved VUV
      PFI-PE spectra for the C(3)H(4) (+)(X (2)E(32,12),nu(1) (+)=1) band. The analysis
      of these PFI-PE spectra leads to the determination of the spin-orbit constant of
      A=-13.0+/-0.2 cm(-1) for the C(3)H(4) (+)(X (2)E(32,12),nu(1) (+)=1) state. Using
      this A constant and the relative rotationally selected and resolved state-to
      state photoionization cross sections thus measured, we have obtained an excellent
      simulation for the VUV-PFI-PE origin band of C(3)H(4) (+)(X (2)E(32,12)),
      yielding a value of 83 619.0+/-1.0 cm(-1) (10.367 44+/-0.000 12 eV) for the
      adiabatic ionization energy of C(3)H(4) [IE(C(3)H(4))]. The present two-color IR
      VUV-PFI-PE study has also made possible the determination of the C-H stretching
      frequencies nu(1) (+)=3217.1+/-0.2 cm(-1) for C(3)H(4) (+)(X (2)E(32,12)). The
      spectral assignment and simulation were guided by high-level ab initio
      calculations on the IE(C(3)H(4)), Franck-Condon factors for photoionization
      transitions, and rotational constants and vibrational frequencies for C(3)H(4)
      (+).

PMID- 18331098
TI  - The study of the D(') (1)Pi(u) state of H(2): transition probabilities from the
      ground state, predissociation yields, and natural linewidths.
AB  - The absorption spectrum of the H(2) molecule was studied at high resolution in
      the 81-72 nm spectral range. A detailed analysis of the D(') (1)Pi(u)-->X
      (1)Sigma(g) (+) electronic band system is reported. In the spectrum, more than 70
      new lines were assigned. For wavelengths longer than 75 nm, the D(') (1)Pi(u) (+)
      and (1)Pi(u) (-) components show a clearly different behavior: Tauhe (1)Pi(u) (+)
      one dissociates into H(1s)+H(n=2) whereas the (1)Pi(u) (-) one leads to molecular
      fluorescence. For shorter wavelengths, both components are predissociated into
      H(1s)+H(n=3). The predissociation yields, the dissociation widths, and the
      absolute values of the transition probabilities were measured over the
      vibrational progression from v(')=3 to 17, i.e., up to the dissociation limit.
      The comparison between these absolute transition probabilities and the values
      calculated in the adiabatic and nonadiabatic approximations demonstrates clearly
      the importance of nonadiabatic couplings.

PMID- 18331099
TI  - Polarizable interaction potential for water from coupled cluster calculations. I.
      Analysis of dimer potential energy surface.
AB  - A six-dimensional interaction potential for the water dimer has been fitted to ab
      initio interaction energies computed at 2510 dimer configurations. These energies
      were obtained by combining the supermolecular second-order energies extrapolated
      to the complete basis set limit from up to quadruple-zeta quality basis sets with
      the contribution from the coupled-cluster method including single, double, and
      noniterative triple excitations computed in a triple-zeta quality basis set. All
      basis sets were augmented by diffuse functions and supplemented by midbond
      functions. The energies have been fitted using an analytic form with the
      induction component represented by a polarizable term, making the potential
      directly transferable to clusters and the bulk phase. Geometries and energies of
      stationary points on the potential surface agree well with the results of high
      level ab initio geometry optimizations.

PMID- 18331100
TI  - Polarizable interaction potential for water from coupled cluster calculations.
      II. Applications to dimer spectra, virial coefficients, and simulations of liquid
      water.
AB  - The six-dimensional CC-pol interaction potential for the water dimer was used to
      predict properties of the dimer and of liquid water, in the latter case after
      being supplemented by a nonadditive potential. All the results were obtained
      purely from first principles, i.e., without any fitting to experimental data.
      Calculations of the vibration-rotation-tunneling levels of (H(2)O)(2) and
      (D(2)O)(2), a very sensitive test of the potential surface, gave results in good
      agreement with experimental high-resolution spectra. Also the virial coefficients
      and properties of liquid water agree well with measured values. The present model
      performs better than published force fields for water in a simultaneous
      reproduction of experimental data for dimer spectra, virials, and properties of
      the liquid.

PMID- 18331101
TI  - Freezing of low energy excitations in charge density wave glasses.
AB  - Thermally stimulated discharge current measurements were performed to study slow
      relaxation processes in two canonical charge density wave systems K(0.3)MoO(3)
      and o-TaS(3). Two relaxation processes were observed and characterized in each
      system, corroborating the results of dielectric spectroscopy. Our results are
      consistent with the scenario of the glass transition on the charge density wave
      superstructure level. In particular, the results directly prove the previously
      proposed criterion of charge density wave freezing based on the interplay of
      charge density wave pinning by impurities and screening by free carriers. In
      addition, we obtained new information on distribution of relaxation parameters,
      as well as on nonlinear dielectric response both below and above the threshold
      field for charge density wave sliding.

PMID- 18331102
TI  - The short-time self-diffusion coefficient of a sphere in a suspension of rigid
      rods.
AB  - The short-time self-diffusion coefficient of a sphere in a suspension of rigid
      rods is calculated in first order in the rod volume fraction phi. For low rod
      concentrations, the correction to the Einstein diffusion constant of the sphere
      due to the presence of rods is a linear function of phi with the slope alpha
      proportional to the equilibrium averaged mobility diminution trace of the sphere
      interacting with a single freely translating and rotating rod. The two-body
      hydrodynamic interactions are calculated using the so-called bead model in which
      the rod of aspect ratio p is replaced by a stiff linear chain of touching
      spheres. The interactions between spheres are calculated using the multipole
      method with the accuracy controlled by a multipole truncation order and limited
      only by the computational power. A remarkable accuracy is obtained already for
      the lowest truncation order, which enables calculations for very long rods, up to
      p=1000. Additionally, the bead model is checked by filling the rod with smaller
      spheres. This procedure shows that for longer rods the basic model provides
      reasonable results varying less than 5% from the model with filling. An
      analytical expression for alpha as a function of p is derived in the limit of
      very long rods. The higher order corrections depending on the applied model are
      computed numerically. An approximate expression is provided, valid for a wide
      range of aspect ratios.

PMID- 18331103
TI  - Wave-pinned filaments of scroll waves.
AB  - Scroll waves are three-dimensional excitation patterns that rotate around one
      dimensional space curves. Typically these filaments are closed loops or end at
      the system boundary. However, in excitable media with anomalous dispersion,
      filaments can be pinned to the wake of traveling wave pulses. This pinning is
      studied in experiments with the 1,4-cyclohexanedione Belousov-Zhabotinsky
      reaction and a three-variable reaction-diffusion model. We show that wave-pinned
      filaments are related to the coexistence of rotating and translating wave defects
      in two dimensions. Filament pinning causes a continuous expansion of the total
      filament length. It can be ended by annihilating the pinning pulse in a frontal
      wave collision. Following such an annihilation, the filament connects itself to
      the system boundary. Its postannihilation shape that is initially the exposed rim
      of the scroll wave unwinds continuously over numerous rotation periods.

PMID- 18331104
TI  - Unidirectional Pt silicide nanowires grown on vicinal Si(100).
AB  - We investigated the structure and electronic properties of unidirectional Pt(2)Si
      nanowires (NWs) grown on a Si(100)-2 degrees off surface. We found that Pt(2)Si
      NWs were formed along the step edges of the Si(100)-2 degrees off surface with
      c(4x6) reconstructions that occurred on the terraces of Si(100) using scanning
      tunneling microscopy and the structure of formed NWs was found to be Pt(2)Si by
      core-level photoemission spectroscopy. Moreover, we confirmed that the electronic
      band structures of the NWs along the NW direction are different from those
      perpendicular to the NWs and the surface state induced by the Pt(2)Si NWs was
      observed with a small density of state using the angle-resolved photoemission
      spectra.

PMID- 18331105
TI  - Multipolar surface plasmon peaks on gold nanotriangles.
AB  - In this paper, we report on the observation of multipolar surface plasmon
      excitation in lithographically designed gold nanotriangles, investigated by means
      of far-field extinction microspectroscopy in the wavelength range of 400-1000 nm.
      Several bands are observed in the visible and near infrared regions when
      increasing the side length of the triangles. The assignment of these peaks to
      successive in-plane multipolar plasmon modes is supported by calculations using
      the discrete dipole approximation method. We show that the lowest three
      multipolar excitations are clearly resolved in the visible and near infrared
      range. These new spectral features could be very promising in nanooptics or for
      chemosensing and biosensing applications.

PMID- 18331106
TI  - Hydrogen dissociation and diffusion on Ni- and Ti-doped Mg(0001) surfaces.
AB  - It is well-known, both theoretically and experimentally, that alloying MgH(2)
      with transition elements can significantly improve the thermodynamic and kinetic
      properties for H(2) desorption, as well as the H(2) intake by Mg bulk. Here, we
      present a density functional theory investigation of hydrogen dissociation and
      surface diffusion over a Ni-doped surface and compare the findings to previously
      investigated Ti-doped Mg(0001) and pure Mg(0001) surfaces. Our results show that
      the energy barrier for hydrogen dissociation on the pure Mg(0001) surface is
      high, while it is small/null when NiTi are added to the surface as dopants. We
      find that the binding energy of the two H atoms near the dissociation site is
      high on Ti, effectively impeding diffusion away from the Ti site. By contrast, we
      find that on Ni, the energy barrier for diffusion is much reduced. Therefore,
      although both Ti and Ni promote H(2) dissociation, only Ni appears to be a good
      catalyst for Mg hydrogenation, allowing diffusion away from the catalytic sites.
      Experimental results corroborate these theoretical findings, i.e., faster
      hydrogenation of the Ni-doped Mg sample as opposed to the reference Mg- or Ti
      doped Mg.

PMID- 18331107
TI  - Electronic structure of cluster assembled nanostructured TiO(2) by resonant
      photoemission at the Ti L(2,3) edge.
AB  - The electronic structure of cluster assembled nanostructured TiO(2) thin films
      has been investigated by resonant photoemission experiments with photon energies
      across the Ti L(2,3) edge. The samples were produced by supersonic cluster beam
      deposition with a pulsed microplasma cluster source. The valence band shows
      resonance enhancements in the binding energy region between 4 and 8 eV, populated
      by O 2p and hybridized Ti 3d states, and in the region about 1 eV below the Fermi
      level associated with defects related Ti 3d states. The data show that in as
      deposited films Ti atoms are mainly fully (sixfolds) coordinated to oxygen atoms
      in octahedral symmetry and only a small fraction is in a broken symmetry
      environment. Since resonant photoemission is closely linked to the local
      electronic and structural configurations around the Ti atom, it is possible to
      correlate the resonant photoemission intensity and lineshape with the presence of
      defects of the films and with the degree of hybridization between the titanium
      and oxygen atoms.

PMID- 18331108
TI  - The influences of particle number on hot spots in strongly coupled metal
      nanoparticles chain.
AB  - In understanding of the hot spot phenomenon in single-molecule surface enhanced
      Raman scattering (SM-SERS), the electromagnetic field within the gaps of dimers
      (i.e., two particle systems) has attracted much interest as it provides
      significant field amplification over single isolated nanoparticles. In addition
      to the existing understanding of the dimer systems, we show in this paper that
      field enhancement within the gaps of a particle chain could maximize at a
      particle number N>2, due to the near-field coupled plasmon resonance of the
      chain. This particle number effect was theoretically observed for the gold (Au)
      nanoparticles chain but not for the silver (Ag) chain. We attribute the reason to
      the different behaviors of the dissipative damping of gold and silver in the
      visible wavelength range. The reported effect can be utilized to design effective
      gold substrate for SM-SERS applications.

PMID- 18331109
TI  - Correlation between the energy shell structure and geometry in metallic
      nanoclusters: quasiresonance states, isotope effect.
AB  - Metallic nanoclusters displaying electronic shell structure exhibit the special
      feature of a correlation between their geometry and the number of delocalized
      electrons. Their shape evolution can be described as a quantum oscillation
      between quasiresonant states (prolate and oblate configurations) whose amplitudes
      depend on the degree of shell filling. The picture explains the evolution of
      absorption spectra and predicts a peculiar isotope effect.

PMID- 18331110
TI  - Thermal stability of graphene edge structure and graphene nanoflakes.
AB  - One of the most exciting recent developments in nanoscience was the discovery of
      graphene (single sheets of carbon atoms, a two-dimensional "(2D) crystal") and
      the subsequent discovery of the fascinating properties of this new material,
      e.g., electrons behaving as massless relativistic particles and an anomalous
      quantum Hall effect [A. K. Geim and K. S. Novoselov, Nat. Mater. 6, 183 (2007)].
      It is also surprising that large sheets of graphene exist as it was widely
      believed that 2D crystals are unstable. Furthermore, because of the stability of
      folded graphene sheets, i.e., carbon nanotubes (CNTs), a fascinating question is
      why does not graphene spontaneously transform into CNTs? In this paper, we
      explore the thermal stability of small pieces of graphene, i.e., graphene
      nanoflakes by ab initio quantum mechanical techniques. We find that indeed
      nanoflakes are stable to being heated and do not under any conditions used here
      transform to CNTs. They do not, however, remain strictly 2D as at finite
      temperatures, they undergo extensive vibrational motion and remain buckled if
      annealed and then quenched to room temperature.

PMID- 18331111
TI  - Simulations of the untying of molecular friction knots between individual polymer
      strands.
AB  - The dynamics of molecular knots is implicated in a broad range of phenomena, from
      DNA replication to relaxation of polymer melts. Motivated by the recent
      experiments, in which biopolymer knots have been observed and manipulated at a
      single-molecule level, we have used computer simulations to study the dynamics of
      "friction knots" joining individual polymer strands. A friction knot splicing two
      ropes becomes jammed when the ropes are pulled apart. In contrast, molecular
      friction knots eventually become undone by thermal motion. We show that depending
      on the knot type and on the polymer structure, a microscopic friction knot can be
      strong (the time tau the knot stays tied increases with the force F applied to
      separate the strands) or weak (tau decreases with increasing F). The strong knot
      behavior is a microscopic analog of macroscopic knot jamming. We further describe
      a simple model explaining these behaviors.

PMID- 18331112
TI  - Identification of the optically active vibrational modes in the photoluminescence
      of MEH-PPV films.
AB  - The temperature dependence of the photoluminescence properties of a thin film of
      poly[2-methoxy-5-(2(')-ethylhexyloxy)-p-phenylene-vinylene], MEH-PPV, fabricated
      by spin coating, is analyzed. The evolution with temperature of the peak energy
      of the purely electronic transition, of the first vibronic band, of the effective
      conjugation length, and of the Huang-Rhys factors are discussed. The asymmetric
      character of the pure electronic transition peak and the contribution of the
      individual vibrational modes to the first vibronic band line shape are considered
      by a model developed by Cury et al. [J. Chem. Phys. 121, 3836 (2004)]. The
      temperature dependence of the Huang-Rhys factors of the main vibrational modes
      pertaining to the first vibronic band allows us to identify two competing
      vibrational modes. These results show that the electron coupling to different
      vibrational modes depends on temperature via reduction of thermal disorder.

PMID- 18331113
TI  - The phase behavior of comblike block copolymer A(m+1)B(m)/homopolymer A mixtures.
AB  - The phase behaviors of comblike block copolymer A(m+1)B(m)/homopolymer A mixtures
      are studied by using the random phase approximation method and real-space self
      consistent field theory. From the spinodals of macrophase separation and
      microphase separation, we can find that the number of graft and the length of the
      homopolymer A have great effects on the phase behavior of the blend. For a given
      composition of comblike block copolymer, increasing the number of graft does not
      change the macrophase separation spinodal curve but decreases the microphase
      separation region. The addition of a small quantity of long-chain homopolymer A
      increases the microphase separation of comblike block copolymer/homopolymer A
      mixture. However, the addition of short-chain homopolymer A will decrease the
      phase separation region of comblike block copolymer/homopolymer A mixture. It is
      also found that the microstructure formed by diblock copolymer is easier to be
      swelled by homopolymer than that formed by comblike block copolymer. This can be
      attributed to the architecture difference between the comblike block copolymer
      and linear block copolymer.

PMID- 18331114
TI  - The impact of health information technology on collaborative chronic care
      management.
AB  - BACKGROUND: Chronic disease is a growing problem in the United States. More than
      125 million Americans had at least 1 chronic care condition in 2000, and this
      number is expected to grow to 157 million by the year 2020.1 Some of the
      challenges associated with current chronic care management approaches can be
      addressed through the use of health information technology (IT) and health
      information exchange. OBJECTIVE: To review the current challenges of chronic care
      management and explore how health IT and health information exchange efforts at
      the national, state, and local levels can be leveraged to address some of these
      challenges. SUMMARY: Efforts to effectively manage chronic care have been
      hampered by a number of factors, including a fragmented health care system and
      the need for more coordination across the health care setting; the lack of
      interoperable clinical information systems, which would help provide readily
      available, comprehensive information about the patient to those who deliver care,
      those who manage care, and those who receive care, and finally, the current
      predominantly fee-for-service reimbursement system that rewards volume and
      fragmentation, and does not effectively align incentives with the goals of
      chronic care management. The introduction of health IT, including electronic
      health records and health information exchange, holds great promise for
      addressing many of the barriers to effective chronic care management, by
      providing important clinical information about the patient when it is needed, and
      where it is needed, in a timely, secure fashion. Having information from the care
      delivery process readily available through health IT and health information
      exchange at the national, state, and local levels supports key components of the
      chronic care management process, including those related to measurement, clinical
      decision support, collaboration and coordination, and consumer activation.
      CONCLUSIONS: Those engaged in chronic care management should seek to leverage
      health IT and health information exchange initiatives particularly at the local
      levels. Community-based initiatives have built social capital and trust across
      multiple stakeholders; enabled access to clinical data derived from the care
      delivery process that only resides locally; and in many cases aligned incentives
      around the mobilization of clinical information across care settings. All of
      these elements are critical to the long-term success of chronic care management.
      While there is good research regarding interdisciplinary care models, more
      research is still needed to identify policies, practices, and strategies for
      facilitating and building cooperation among those engaged in chronic care
      management, and those engaged in multi-stakeholder efforts involved in the
      exchange of clinical health information electronically.

PMID- 18331115
TI  - Information technology for the treatment of diabetes: improving outcomes and
      controlling costs.
AB  - BACKGROUND: Diabetes in particular presents an ideal opportunity for the
      incorporation of information technology (IT) in the provision of care. The
      disease is highly prevalent in managed care populations, is frequently associated
      with comorbid conditions, and requires multiple medications in its management.
      Furthermore, effective diabetes care involves the monitoring of several measures
      of disease control, such as hemoglobin A1c (A1c) and lipid levels, by several
      different levels of providers, such as physicians, nurse practitioners, physician
      assistants, pharmacists, and dieticians. All of these factors combined make
      diabetes an opportune disease state for a case study of the implementation of
      health information technology (HIT) in managed care. OBJECTIVE: To review
      practical applications of HIT for improving the delivery of care in diabetes
      management. SUMMARY: Between 1990 and 2002, the incidence of type 2 diabetes
      increased by 61% in the United States. The total costs associated with diabetes
      have been increasing since the late 1970s as well, with a more dramatic rise over
      the last 10 years. In fact, the total cost of diabetes in the United States will
      approach $200 billion per year by the year 2020. In order to improve diabetes
      management efforts nation wide, the goal of glucose lowering therapy has been
      recommended to lower the hemoglobin A1c (A1c) to < 7% and keep it below that
      level long term. Other measures beyond A1c levels have also been identified as
      being important components to effective diabetes management and incorporated into
      national treatment recommendations, providing an ideal opportunity for the
      incorporation of HIT interventions. These interventions have been aimed at 3
      different groups of stakeholders in managed care: payers, providers, and
      patients. CONCLUSIONS: While uncontrolled diabetes remains a major concern in
      managed care from both a health and a cost perspective, implementation of
      information technology enabled diabetes management (ITDM) has demonstrated
      significant potential for improving processes of care, preventing the development
      of diabetic complications, and generating cost savings. ITDM improves the
      synthesis of information, the delivery of knowledge, and the efficiency of
      communication, allowing for coordination of care across delivery teams. Of the
      existing technologies targeting providers, patients, and payers, provider
      centered interventions, such as diabetes registries currently show the most
      potential for benefit in improving outcomes and reducing costs.

PMID- 18331116
TI  - Operationalizing MTM through the use of health information technology.
AB  - BACKGROUND: Health information technology (HIT) tools are needed to sort the ever
      increasing volume of available clinical data, and thereby allow patients,
      practitioners, and health plans to understand and use the data to its fullest
      potential By harnessing this potential, managed care organizations (MCOs) will
      see improvements in the quality of health care and ultimately reduced costs.
      Furthermore, HIT offers the ability to help improve communication channels to
      share the increasing amounts of information available to MCOs today. In effect,
      medication therapy management (MTM) programs are using HIT to identify an at-risk
      population and reach that population in the most appropriate measure. OBJECTIVE:
      To identify and review the design components of an operationally effective MTM
      program, including the services offered. The use of HIT in quality improvement
      initiatives at managed care plans will also be reviewed. SUMMARY: The operational
      components of MTM programs that rely heavily on HIT include patient
      identification, stratification of care, coordination of care, and safety
      evaluation. Primarily, HIT plays a significant role in identifying the services
      offered to MTM program patients in MCOs. For example, the Humana MTM program
      offers personalized educational mailings, telephone consultations, and face-to
      face consultations with the community pharmacist. Within the plan, HIT is used to
      score and stratify eligible patients according to these available services. HIT
      is further employed to coordinate the collective efforts of pharmacists and
      physicians in the administration of care, as well as to monitor medication safety
      measures. Health plans gain a greater ability to improve the quality of care for
      their patients through proper application of HIT. The opportunities exist both
      internally at the plan and externally partnered with other organizations. Quality
      improvement begins with proper recording and tracking of quality measures and
      then the development of quality improvement projects in an effort to improve the
      process of care and the resulting health outcomes. CONCLUSIONS: As the amount of
      data available to managed care stakeholders increases, HIT is becoming a crucial
      tool for sorting and stratifying the information. MTM programs provide another
      example of the application of HIT in managed care, with involvement on every
      level of the care continuum: payers, providers, and patients. Services offered by
      MTM programs are useful and varied, including process-improving initiatives, such
      as personalized educational mailings, telephone consultations, and face-to-face
      consultations with the community pharmacist. The end result is quality
      improvement in the delivery of care with a focus on improving medication
      adherence and safety.

PMID- 18331117
TI  - Actual versus projected cost avoidance for clinical pharmacy specialist-initiated
      medication conversions in a primary care setting in an integrated health system.
AB  - BACKGROUND: Primary care clinical pharmacy specialists (PCCPSs) are positioned to
      promote effective, safe, and affordable medication use. Documentation of
      performed interventions is difficult because the diversity of performed
      interventions in a variety of disease states in some practice settings.
      Validation of cost-avoidance projections is also difficult because traditional
      projection methods have several limitations. OBJECTIVE: To (1) compare projected
      medication cost avoidance (MCA) to actual MCA for medication conversions related
      to hyperlipidemia, hypertension, depression, and chronic pain initiated by PCCPS,
      and (2) estimate medication discontinuation that might be attributable to serious
      adverse drug events (ADEs) possibly associated with medication conversions.
      METHODS: This was a retrospective, longitudinal study conducted in a not-for
      profit, integrated health system comprising approximately 470,000 members. Using
      a portable documentation tool, PCCPSs recorded projected annual MCA for
      medication conversions in 4 disease conditions (i.e., hypertension, dyslipidemia,
      depression, and chronic pain) in the 6-month period from December 1, 2003,
      through May 31, 2004. Actual annual MCA for these interventions for a 1-year
      follow-up period was calculated using integrated, electronic data from an
      administrative pharmacy database. Comparisons were made between projected MCA and
      actual MCA. Cost was defined as actual drug acquisition cost. In addition, an
      assessment of serious ADEs potentially related to the conversions was undertaken
      by reviewing electronic medical records of converted, nonpersistent patients.
      RESULTS: There were 704 medication conversions for 656 patients, of which 47
      (6.7%) were for members who disenrolled in the health plan during the 12 months
      following the medication conversion date. The total projected MCA was $327,337 in
      2004 dollars, or an average of $465 per conversion. For the 657 medication
      conversions in 609 patients that were evaluable (i.e., the member remained
      enrolled through 12 months follow-up), 466 (70.9%) persisted at 12 months, 138
      (21.0%) discontinued the medication or converted to an alternative therapy, and
      53 (8.1%) reverted to the original medication. Drug cost information was not
      available for some members, leaving approximately half (n = 331, 50.4%) of the
      657 evaluable medication conversions with complete cost information available.
      For these 331 conversions, the overall projected MCA overestimated the actual MCA
      by 14.1% ($24,888 in aggregate or an average of $75 per conversion, P < 0.001).
      For persistent medication conversions with complete cost information (n = 278),
      the projected MCA ($160,225) was not significantly different compared with the
      actual MCA ($166,546, P = 0.477). For medication conversions that reverted to
      previous therapy (n = 53), the projected MCA ($41,644) overestimated by 4-fold
      the actual MCA ($10,435, P < 0.001). There were no emergency department visits or
      hospital admissions related to nonpersistent medication conversions. Compared
      with patients who were either nonpersistent or disenrolled at the 12-month follow
      up, persistent patients did not significantly differ in chronic disease score but
      were slightly older (mean = 62.6 years, standard deviation = 13.1 for persistent
      patients vs. 59.2 [SD = 15.5] for nonpersistent or disenrolled patients).
      CONCLUSIONS: Projected medication cost avoidance for pharmacistinitiated
      medication conversions is valid for the 66% of medication conversions that
      persist but not for nonpersistent conversions or for patients who leave the
      health care system. The projected medication cost avoidance overestimated the
      actual cost avoidance by approximately 14%, suggesting that there is opportunity
      for improvement in the tool used to document medication conversions to more
      accurately measure cost outcomes from clinical pharmacy interventions.

PMID- 18331118
TI  - Disease-related and all-cause health care costs of elderly patients with gout.
AB  - BACKGROUND: Gout is a common cause of inflammatory arthritis in the United
      States, and its prevalence has increased in recent decades, especially among
      older adults. Older adults with gout are of particular interest because they tend
      to experience higher rates of tophi, an advanced stage of gout, than do younger
      patients. OBJECTIVE: For older adults with gout to (1) assess health care
      utilization and costs from a third-party payer perspective; (2) evaluate health
      care costs related to tophi; and (3) explore the relationship between elevated
      serum uric acid (UA) level, an indicator of disease control, and health care
      utilization. METHODS: Data were extracted from the Integrated Healthcare
      Information Services (IHCIS) claims database (1999-2005), which includes
      approximately 40 private health plans in the United States for approximately 13
      million beneficiaries, about 4% of whom are aged 65 years or older. Patients were
      included in the study if they: (1) had 2 diagnoses of gout (International
      Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code
      of 274.xx) on separate medical claims or 1 gout diagnosis plus at least 1 gout
      related pharmacy claim (i.e., allopurinol, probenecid, colchicines, or
      sulfinpyrazone); (2) were at least 65 years old at the first diagnosis date
      (study index date); and (3) had 1 year of continuous eligibility both before and
      after the study index date. A comparison sample of elderly members without gout
      was selected using a 1:1 match to gout patients based on age, gender, and
      geographic region. Individuals in the comparison group also had 1 year of
      continuous eligibility both before and after the study index date, defined as the
      same index date as the respective matched gout patient. Patients with possible
      tophi were identified from at least 1 medical claim with an ICD-9-CM code 274.8x
      (274.81=gouty tophi of the ear; 274.82 = gouty tophi of other sites except ear;
      274.89 = gout with other specified manifestations) during the 12-month study
      period following the study index date. Additionally, a subgroup of gout patients
      with at least 1 serum UA measure was selected. Patients were divided into 3
      groups according to their serum UA level on the earliest test date (serum UA
      index date): low (< 6 mg per dL), moderate-high (6-8.99 mg per dL), and very high
      (> or = 9 mg per dL). Health care utilization was categorized into inpatient
      services, outpatient services, emergency room services, other medical services,
      and use of prescription drugs. Medical services were classified by the place of
      service indicated in the claim. Medical services costs and pharmacy costs were
      defined as the amount paid to the provider plus member cost share (e.g.,
      deductible, copayment). Two types of costs were assessed in the analysis: total
      all-cause health care costs and gout-related costs, defined as costs associated
      with a claim with a primary or secondary diagnosis of gout (ICD-9-CM code
      274.xx). Differences in total all-cause health care costs were calculated by
      comparing (1) gout patients and gout-free members during the 12-month period
      following the study index date; (2) gout patients with and without tophi during
      the 12-month period following the study index date; and (3) gout patients across
      the 3 serum UA categories during the 12-month period following the serum UA index
      date. Multivariate regression analyses were used to control for patients'
      baseline demographics, prior comorbidities indicated by the Deyo-Charlson
      Comorbidity Index, and number of medications used during the 12 months prior to
      the study index date. RESULTS: Over the 7 years of claims data through 2005,
      there were 11,935 gout patients aged 65 years or older. The sample had an average
      age of 71.4 years and was predominantly male (73.5%). In the 12 months following
      the study index date, the mean unadjusted per-patient gout-related health care
      cost was $876 (standard deviation $3,373) in 2005 dollars, 5.9% of the total all
      cause health care cost of $14,734 (SD $27,401) for gout patients. Unadjusted
      total 12-month all-cause health care cost for the gout-free members was $9,219
      (SD $20,186). After statistical adjustment for comorbidities, the difference in
      total 12-month all-cause health care costs between gout patients and gout-free
      members was $3,038 (P < 0.001). A diagnosis suggesting possible tophi was found
      in 2.0% (n = 240) of gout patients in the sample. After statistical adjustment
      for comorbidities, the difference in total 12-month all-cause health care costs
      between gout patients with and without tophi was $5,501 (P < 0.001), and the
      difference in total adjusted 12-month gout-related costs between patients with
      and without tophi was $1,710 (P < 0.001). Among the 2,237 (18.7%) patients with
      at least 1 serum UA measure, 28.3% had a low serum UA level, 52.4% had a moderate
      high serum UA level, and 19.3% had a very high serum UA level. For patients with
      low, moderate-high, and very high serum UA levels, regression-adjusted gout
      related costs in the 12 months following the serum UA index date represented,
      respectively, 2.9%, 2.7%, and 3.9% of total regression-adjusted health care
      costs. The group with a very high serum UA level had significantly higher
      regression-adjusted total 12-month all-cause health care costs and gout-related
      costs compared with those with a low serum UA level ($3,103 and $276 higher,
      respectively). CONCLUSIONS: Elderly patients with a diagnosis of gout have higher
      all-cause health care utilization and costs compared with matched elderly
      patients without a diagnosis of gout. Gout-related costs represent about 6% of
      total health care costs in elderly patients with gout. Very high serum UA levels
      (i.e., > or = 9 mg per dL) and diagnoses suggesting possible tophi are associated
      with increased utilization and costs in elderly gout patients.

PMID- 18331119
TI  - Economic burden in direct costs of concomitant chronic obstructive pulmonary
      disease and asthma in a Medicare Advantage population.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a highly prevalent
      disease whose sufferers consume a large amount of resources. Among community
      dwelling Medicare beneficiaries, 12% reported that they had COPD in 2002. For
      clinicians, differentiating COPD from asthma may be difficult, but among patients
      with COPD and asthma, approximately 20% have both conditions. The economic impact
      of concomitant asthma and COPD is potentially large but has not been studied.
      OBJECTIVE: To assess the cost burden of asthma in patients with COPD in a
      Medicare Advantage population. METHODS: We reviewed the database of a large
      health plan that contained information from more than 30 distinct plans covering
      approximately 25 million members. We identified Medicare beneficiaries aged 40
      years or older with medical and pharmacy benefits and medical claims with
      International Classification of Diseases, Ninth Revision, Clinical Modification
      (ICD-9-CM) diagnosis codes for COPD or asthma over a 1-year identification period
      (calendar year 2004). We assigned patients to 2 cohorts based on diagnoses on
      medical claims (any diagnosis field) during 2004; the COPD cohort had at least 1
      medical claim for COPD, and the COPD + asthma cohort had at least 1 claim for
      COPD and at least 1 claim for asthma. A patient's index date was the first date
      during 2004 in which there was a medical claim with a diagnosis code for COPD or
      asthma. To confirm diagnosis, each patient was required to have at least 1
      additional claim for COPD (COPD cohort) or at least 1 claim for COPD and at least
      1 claim for asthma (COPD + asthma cohort) during the 24-month period from 12
      months before through 12 months after the index date. We excluded patients who
      (1) were not continuously enrolled during the 12 months before and after the
      index date and (2) did not have at least 1 pharmacy claim for a drug of any type
      (to verify pharmacy benefits). Outcome measures included the use of emergency
      room (ER) and hospital services, and cost (net provider payment after subtraction
      of member cost share), categorized as all-cause, non-respiratory, and respiratory
      related. ER use and inpatient hospital stays were identified using place-of
      service codes. A minimum of 2 consecutive dates of service (length of stay [LOS]
      of at least 1 day) was required to indicate an inpatient hospitalization. An LOS
      of at least 1 day was required to distinguish inpatient services from other
      services (e.g., procedures or tests) reported on claims with an inpatient place
      of service. Multivariate analyses adjusted for age, gender, census region, and
      Charlson Comorbidity Index (CCI). Ordinary least squares regression was used to
      predict respiratory-related total health care costs, and logistic regression was
      used to predict the occurrence of at least 1 acute event, defined as use of
      either an ER or an inpatient hospital. All 2-way interactions were considered,
      and only those with significant results were included in the models. All reported
      P values were 2-sided with a 0.05 significance level. RESULTS: During 2004,
      68,532 individuals within the database were enrolled in a Medicare Advantage
      plan. After application of the other inclusion criteria, we excluded
      approximately 11% of the patients who did not have 1 pharmacy claim of any type.
      There were 8,086 patients (11.8%) who had at least 1 medical claim with diagnosis
      codes for COPD and at least 1 other medical claim for either COPD or asthma and
      were continuously enrolled for at least 24 months. The COPD + asthma cohort
      numbered 1,843 patients (22.8%), and the COPD cohort numbered 6,243 patients
      (77.2%). Compared with COPD patients without asthma, patients with COPD + asthma
      were slightly younger, and a higher proportion was female. There were differences
      between the 2 cohorts in geographic distribution, and the COPD + asthma cohort
      had a higher disease severity with a mean CCI score of 2.6 (standard deviation
      [SD], 2.1) compared with the COPD cohort (2.3 [2.3], P < 0.001). Respiratory
      related pharmacy costs were a relatively small part of total respiratory-related
      health care costs: approximately 5.7% for the COPD cohort and 8.8% for the COPD +
      asthma cohort. Respiratory-related costs accounted for 22.0% of total all-cause
      health care costs for the COPD cohort and 28.7% for the COPD + asthma cohort.
      Mean ([SD], median) unadjusted respiratory-related health care costs were $7,240
      ([$15,057], $1,957) for the COPD + asthma cohort and $5,158 ([$11,881], $808) in
      the COPD cohort. After adjusting for covariates, patients in the COPD + asthma
      cohort were more likely to have at least 1 acute event (e.g., ER visits and
      hospitalizations) than patients in the COPD cohort (adjusted odds ratio, 1.6; 95%
      CI, 1.4-1.7) and had $1,931 (37.1%) greater adjusted respiratory-related health
      care costs--$7,135 versus $5,204 for the COPD cohort (P < 0.001). CONCLUSION:
      Medicare beneficiaries with COPD and asthma incur higher health care costs and
      use more health care services than those with COPD without asthma.

PMID- 18331120
TI  - Opioid drug utilization and cost outcomes associated with the use of
      buprenorphine-naloxone in patients with a history of prescription opioid use.
AB  - BACKGROUND: Management of opioid dependence is associated with many challenges
      such as the misuse of prescribed treatment and lack of medication adherence that
      can affect the clinical outcome of the patient. Buprenorphine-naloxone was
      approved by the U.S. Food and Drug Administration in October 2002 as the first
      outpatient treatment indicated for opioid dependence. There is only 1 report in
      the literature on the effectiveness of buprenorphine-naloxone in a real-world
      setting and no reports on persistence and cost obtained from administrative
      claims data. OBJECTIVES: To determine (1) the length and cost of therapy with
      oral buprenorphine-naloxone, and (2) the cost avoidance for opioid dependence as
      measured by opioid utilization and opioid drug cost obtained from pharmacy claim
      records. METHODS: The patients for this drug use evaluation (DUE) were identified
      from a New Jersey managed care organization (MCO) with approximately 1.8 million
      members with pharmacy benefits who (a) were continuously enrolled from October 1,
      2004, through September 30, 2006; (b) had their first buprenorphine-naloxone
      pharmacy claim during the fixed 6-month initiation period (April 1, 2005, through
      September 30, 2005); and (c) had at least 1 opioid pharmacy claim in the 6-month
      pre period preceding the 6-month initiation period. The outcome measures included
      the number of opioid pharmacy claims, daily dose, days supply, and cost defined
      as opioid ingredient cost. Member cost share and net plan cost (after subtraction
      of member cost share) were also measured. The measurement periods for opioid use
      and cost were the fixed calendar periods for 6 months from October 1, 2004,
      through March 31, 2005, and for 12 months from October 1, 2005, through September
      30, 2006. Persistence in the 12-month follow-up period was defined as a gap of 30
      days or less between depletion of the days supply for the preceding pharmacy
      claim for buprenorphinenaloxone and the date of service (refill date) for the
      succeeding pharmacy claim for buprenorphine-naloxone. RESULTS: Of the 160 new
      buprenorphine-naloxone users with continuous pharmacy enrollment for the 2-year
      period ending September 30, 2006, 84 patients (52.5%) had at least 1 opioid
      pharmacy claim in the 6-month pre period from October 1, 2004, through March 31,
      2005, and were included in this DUE. In the 12-month post period from October 1,
      2005, through September 2006, the median length of therapy with
      buprenorphinenaloxone was 1 month, and the mean length of therapy was 3.5 months.
      Only 40 patients (47.6%) had a pharmacy claim for buprenorphine-naloxone at month
      1 in the 12-month post period. Persistence was 27.4% (n = 23) at 6 months (March
      2006) and 20.2% (n = 17) at 12 months (September 2006) in the post period. A
      total of 24 study patients (28.6%) had no opioid pharmacy claims other than
      buprenorphine-naloxone in the 12-month post period. Utilization of opioids
      decreased by 18.8%, from 1.49 opioid pharmacy claims per patient per month (PPPM)
      in the pre period to 1.21 claims PPPM in the post period (P = 0.031). Excluding
      the 0.42 buprenorphine-naloxone claims PPPM, opioid utilization decreased by
      47.0%, from 1.49 claims PPPM to 0.79 claims PPPM (P < 0.001) in the 12-month post
      period. Before subtraction of member cost share, the actual drug cost of opioids
      including buprenorphine-naloxone appeared to be 26.9% lower ($156.24 PPPM) in the
      post period compared with $213.74 PPPM in the pre period, but the difference was
      not statistically significant (P = 0.254). Excluding the cost of the
      buprenorphine-naloxone, actual opioid drug cost decreased 66.5% from $213.74 PPPM
      pre period to $71.65 PPPM post period (P = 0.047). CONCLUSIONS: Approximately one
      half of the patients who had a new claim for buprenorphine-naloxone were excluded
      from this study because there was no utilization of prescription opioids in the 6
      months prior to initiation. For patients with documented use of prescription
      opioids prior to initiation, treatment with buprenorphine-naloxone was associated
      with a reduction in opioid utilization and cost in the first year of follow-up.
      Persistence was only 27% at 6 months and 20% at 12 months, and there were no drug
      cost savings in the follow-up period when the actual cost of the buprenorphine
      naloxone therapy was included.

PMID- 18331121
TI  - Is buprenorphine-naloxone ready for prime time in the treatment of opioid
      addiction in managed care?

PMID- 18331122
TI  - Making the world safe for evidence-based policy: let's slay the biases in
      research on value-based insurance design.

PMID- 18331123
TI  - New methods for new questions: obstacles and opportunities.
AB  - Two forces motivate this special section, "New Methods for New Questions in
      Developmental Psychology." First are recent developments in social science
      methodology and the increasing availability of those methods in common software
      packages. Second, at the same time psychologists' understanding of developmental
      phenomena has continued to grow. At their best, these developments in theory and
      methods work in tandem, fueling each other. Newer methods make it possible for
      scientists to better test their ideas; better ideas lead methodologists to
      techniques that better reflect, capture, and quantify the underlying processes.
      The articles in this special section represent a sampling of these new methods
      and new questions. The authors describe common themes in these articles and
      identify barriers to future progress, such as the lack of data sharing by and
      analytical training for developmentalists.

PMID- 18331124
TI  - Effects of the family environment: gene-environment interaction and passive gene
      environment correlation.
AB  - The classical twin study provides a useful resource for testing hypotheses about
      how the family environment influences children's development, including how genes
      can influence sensitivity to environmental effects. However, existing statistical
      models do not account for the possibility that children can inherit exposure to
      family environments (i.e., passive gene-environment correlation). The authors
      introduce a method to simultaneously estimate the effects of passive gene-
      environment correlation and gene- environment interaction and use it to
      investigate the relationship between chaos in the home and verbal ability in a
      large sample of 4-year-old twins.

PMID- 18331125
TI  - Growth curve models for indistinguishable dyads using multilevel modeling and
      structural equation modeling: the case of adolescent twins' conflict with their
      mothers.
AB  - Growth modeling is a useful tool for studying change over time, and it is
      becoming increasingly popular with developmental researchers. There is a
      considerable methodological literature surrounding growth modeling for
      individuals; however, far less attention has been focused on growth models for
      pairs of related individuals (i.e., dyads). In this article, the authors consider
      dyadic growth models for those cases where there are no relevant variables that
      can empirically distinguish between dyad members (e.g., same-sex twins or best
      friends). The authors describe how researchers can estimate growth models for
      indistinguishable dyads using both multilevel modeling and structural equation
      modeling. Although both approaches can be used to estimate the same underlying
      models, the authors focus on practical similarities and differences between the
      two approaches. They illustrate modeling issues using an overtime study of
      adolescent twins' conflict with their mothers, a substantively important topic
      given the enduring interest in parent-child relationships during adolescence.

PMID- 18331126
TI  - Diverse pathways to positive and negative affect in adulthood and later life: an
      integrative approach using recursive partitioning.
AB  - Recursive partitioning is an analytic technique that is useful for identifying
      complex combinations of conditions that predict particular outcomes as well as
      for delineating multiple subgroup differences in how such factors work together.
      As such, the methodology is well suited to multidisciplinary, life course inquiry
      in which the goal is to integrate many interacting influences and understand
      subgroup variation. The authors conducted recursive partitioning analyses on a
      previously published study (D. K. Mroczek & C. M. Kolarz, 1998) that investigated
      life course profiles of positive and negative affect and incorporated various top
      down (personality traits) and bottom-up (sociodemographic statuses, contextual
      influences) influences. The new analyses reveal multiway, nonlinear interactions
      among these variables in predicting affective experience and, importantly, life
      course differences in how these various factors combine. Included are details of
      how recursive partitioning trees are generated as well as descriptions of the
      software packages available for using such techniques. Overall, the methodology
      offers tractable strategies for discerning meaningful patterns in highly complex
      data sets.

PMID- 18331127
TI  - Mixing qualitative and quantitative research in developmental science: uses and
      methodological choices.
AB  - Multiple methods are vital to understanding development as a dynamic,
      transactional process. This article focuses on the ways in which quantitative and
      qualitative methodologies can be combined to enrich developmental science and the
      study of human development, focusing on the practical questions of "when" and
      "how." Research situations that may be especially suited to mixing qualitative
      and quantitative approaches are described. The authors also discuss potential
      choices for using mixed quantitative- qualitative approaches in study design,
      sampling, construction of measures or interview protocols, collaborations, and
      data analysis relevant to developmental science. Finally, they discuss some
      common pitfalls that occur in mixing these methods and include suggestions for
      surmounting them.

PMID- 18331128
TI  - Using technology to explore social networks and mechanisms underlying peer
      effects in classrooms.
AB  - Peer interactions among children have long interested social scientists.
      Identifying causal peer effects is difficult, and a number of studies have used
      random assignment to produce evidence that peers affect each other's outcomes.
      This focus by sociologists and economists on whether peers affect each other has
      not been matched by direct evidence on how these effects operate. The authors
      argue that one reason for the small number of studies in sociology and economics
      on the mechanisms underlying peer effects is the difficulty of collecting data on
      microinteractions. They argue technology reduces data collection costs relative
      to direct observation and allows for realistic school activities with randomly
      assigned peers. The authors describe a novel strategy for collecting data on peer
      interactions and discuss how this approach might shed light on mechanisms
      underlying peer influence. The centerpiece of this strategy is the use of
      handheld computers by middle and high school students as part of interactive math
      and science lessons called the Discussion Game. The handhelds collect data on
      interactions between students and track how students' answers evolve as they
      interact with different peers.

PMID- 18331129
TI  - Pooling data from multiple longitudinal studies: the role of item response theory
      in integrative data analysis.
AB  - There are a number of significant challenges researchers encounter when studying
      development over an extended period of time, including subject attrition, the
      changing of measurement structures across groups and developmental periods, and
      the need to invest substantial time and money. Integrative data analysis is an
      emerging set of methodologies that allows researchers to overcome many of the
      challenges of single-sample designs through the pooling of data drawn from
      multiple existing developmental studies. This approach is characterized by a host
      of advantages, but this also introduces several new complexities that must be
      addressed prior to broad adoption by developmental researchers. In this article,
      the authors focus on methods for fitting measurement models and creating scale
      scores using data drawn from multiple longitudinal studies. The authors present
      findings from the analysis of repeated measures of internalizing symptomatology
      that were pooled from three existing developmental studies. The authors describe
      and demonstrate each step in the analysis and conclude with a discussion of
      potential limitations and directions for future research.

PMID- 18331130
TI  - From statistical associations to causation: what developmentalists can learn from
      instrumental variables techniques coupled with experimental data.
AB  - In this article, the authors aim to make accessible the careful application of a
      method called instrumental variables (IV). Under the right analytic conditions,
      IV is one promising strategy for answering questions about the causal nature of
      associations and, in so doing, can advance developmental theory. The authors
      build on prior work combining the analytic approach of IV with the strengths of
      random assignment design, whether the experiment is conducted in the lab setting
      or in the "real world." The approach is detailed through an empirical example
      about the effects of maternal education on children's cognitive and school
      outcomes. With IV techniques, the authors address whether maternal education is
      causally related to children's cognitive development or whether the observed
      associations reflect some other characteristic related to parenting, income, or
      personality. The IV estimates show that maternal education has a positive effect
      on the cognitive test scores of children entering school. The authors conclude by
      discussing opportunities for applying these same techniques to address other
      questions of critical relevance to developmental science.

PMID- 18331131
TI  - Using full matching to estimate causal effects in nonexperimental studies:
      examining the relationship between adolescent marijuana use and adult outcomes.
AB  - Matching methods such as nearest neighbor propensity score matching are
      increasingly popular techniques for controlling confounding in nonexperimental
      studies. However, simple k:1 matching methods, which select k well-matched
      comparison individuals for each treated individual, are sometimes criticized for
      being overly restrictive and discarding data (the unmatched comparison
      individuals). The authors illustrate the use of a more flexible method called
      full matching. Full matching makes use of all individuals in the data by forming
      a series of matched sets in which each set has either 1 treated individual and
      multiple comparison individuals or 1 comparison individual and multiple treated
      individuals. Full matching has been shown to be particularly effective at
      reducing bias due to observed confounding variables. The authors illustrate this
      approach using data from the Woodlawn Study, examining the relationship between
      adolescent marijuana use and adult outcomes.

PMID- 18331132
TI  - Effects of kindergarten retention on children's social-emotional development: an
      application of propensity score method to multivariate, multilevel data.
AB  - This study examines the effects of kindergarten retention on children's social
      emotional development in the early, middle, and late elementary years. Previous
      studies have generated mixed results partly due to some major methodological
      challenges, including selection bias, measurement error, and divergent
      perceptions of multiple respondents in different domains of child development.
      The authors address these challenges by using propensity score stratification to
      contend with selection bias and by embedding measurement models in hierarchical
      models to account for measurement error and to model dependence among
      observations. The authors' analyses of a series of multivariate models enable
      them to compare the retention effects across different respondents over different
      time points. In general, the results show no evidence suggesting that
      kindergarten retention does harm to children's social-emotional development.
      Rather, the findings suggest that, had the retained kindergartners been promoted
      to the first grade instead, they would possibly have developed a lower level of
      self-confidence and interest in reading and all school subjects 2 years later and
      would have displayed a higher level of internalizing problem behaviors at the end
      of the treatment year and 2 years later.

PMID- 18331133
TI  - Combining group-based trajectory modeling and propensity score matching for
      causal inferences in nonexperimental longitudinal data.
AB  - A central theme of research on human development and psychopathology is whether a
      therapeutic intervention or a turning-point event, such as a family break-up,
      alters the trajectory of the behavior under study. This article describes and
      applies a method for using observational longitudinal data to make more
      transparent causal inferences about the impact of such events on developmental
      trajectories. The method combines 2 distinct lines of research: work on the use
      of finite mixture modeling to analyze developmental trajectories and work on
      propensity score matching. The propensity scores are used to balance observed
      covariates and the trajectory groups are used to control pretreatment measures of
      response. The trajectory groups also aid in characterizing classes of subjects
      for which no good matches are available. The approach is demonstrated with an
      analysis of the impact of gang membership on violent delinquency based on data
      from a large longitudinal study conducted in Montreal, Canada.

PMID- 18331134
TI  - Temporal patterns of variable relationships in person-oriented research:
      longitudinal models of configural frequency analysis.
AB  - This article reviews the premises of configural frequency analysis (CFA),
      including methods of choosing significance tests and base models, as well as
      protecting alpha, and discusses why CFA is a useful approach when conducting
      longitudinal person-oriented research. CFA operates at the manifest variable
      level. Longitudinal CFA seeks to identify those temporal patterns that stand out
      as more frequent (CFA types) or less frequent (CFA antitypes) than expected with
      reference to a base model. A base model that has been used frequently in CFA
      applications, prediction CFA, and a new base model, auto-association CFA, are
      discussed for analysis of cross-classifications of longitudinal data. The former
      base model takes the associations among predictors and among criteria into
      account. The latter takes the auto-associations among repeatedly observed
      variables into account. Application examples of each are given using data from a
      longitudinal study of domestic violence. It is demonstrated that CFA results are
      not redundant with results from log-linear modeling or multinomial regression and
      that, of these approaches, CFA shows particular utility when conducting person
      oriented research.

PMID- 18331135
TI  - A new SAS procedure for latent transition analysis: transitions in dating and
      sexual risk behavior.
AB  - The set of statistical methods available to developmentalists is continually
      being expanded, allowing for questions about change over time to be addressed in
      new, informative ways. Indeed, new developments in methods to model change over
      time create the possibility for new research questions to be posed. Latent
      transition analysis, a longitudinal extension of latent class analysis, is a
      method that can be used to model development in discrete latent variables, for
      example, stage processes, over 2 or more times. The current article illustrates
      this approach using a new SAS procedure, PROC LTA, to model change over time in
      adolescent and young adult dating and sexual risk behavior. Gender differences
      are examined, and substance use behaviors are included as predictors of initial
      status in dating and sexual risk behavior and transitions over time.

PMID- 18331136
TI  - An overview of Markov chain methods for the study of stage-sequential
      developmental processes.
AB  - This article presents an overview of quantitative methodologies for the study of
      stage-sequential development based on extensions of Markov chain modeling. Four
      methods are presented that exemplify the flexibility of this approach: the
      manifest Markov model, the latent Markov model, latent transition analysis, and
      the mixture latent Markov model. A special case of the mixture latent Markov
      model, the so-called mover-stayer model, is used in this study. Unconditional and
      conditional models are estimated for the manifest Markov model and the latent
      Markov model, where the conditional models include a measure of poverty status.
      Issues of model specification, estimation, and testing using the Mplus software
      environment are briefly discussed, and the Mplus input syntax is provided. The
      author applies these 4 methods to a single example of stage-sequential
      development in reading competency in the early school years, using data from the
      Early Childhood Longitudinal Study--Kindergarten Cohort.

PMID- 18331137
TI  - Testing the degree of cross-sectional and longitudinal dependence between two
      discrete dynamic processes.
AB  - Developmental research often involves studying change across 2 or more processes
      or constructs simultaneously. A natural question in this work is whether change
      in these 2 processes is related or independent. Associative latent transition
      analysis (ALTA) was designed to test hypotheses about the degree to which change
      in 2 discrete latent variables is related. The ALTA model is a type of latent
      class model, which is a categorical latent variable model based on categorical
      indicators. In the ALTA approach, level and change on 1 variable is predicted by
      level and change in another. Two types of hypotheses are discussed: (a) broad
      hypotheses of dependence between the 2 discrete latent variables and (b) targeted
      hypotheses comparing specific patterns of change between levels of the discrete
      variables. Both types of hypotheses are tested via nested model comparisons.
      Analyses of relations between psychological state and substance use illustrate
      the model. Recent psychological state and recent substance use were found to be
      associated cross-sectionally and longitudinally, implying that change in recent
      substance use was related to change in recent psychological state.

PMID- 18331139
TI  - Personal homepage construction as an expression of social development.
AB  - In 2 studies, the authors explored preadolescent and adolescent use of personal
      homepages in relation to mastery and identity formation. In Study 1, the authors
      attempted to determine the prevalence of personal homepage and online journal
      (blog) construction among a random sample (N=500) of preadolescents and
      adolescents. Adolescents were more likely to create personal homepages or blogs
      than preadolescents. Creation was related to feelings of mastery, expressions of
      identity, and a means to socialize. In Study 2, the authors explored the
      relationship of homepages to mastery and identity formation by content analysis
      of a random sample of homepages. Results suggest children use personal homepages
      to express and explore their forming identities.

PMID- 18331138
TI  - Finding groups using model-based cluster analysis: heterogeneous emotional self
      regulatory processes and heavy alcohol use risk.
AB  - Model-based cluster analysis is a new clustering procedure to investigate
      population heterogeneity utilizing finite mixture multivariate normal densities.
      It is an inferentially based, statistically principled procedure that allows
      comparison of nonnested models using the Bayesian information criterion to
      compare multiple models and identify the optimum number of clusters. The current
      study clustered 36 young men and women on the basis of their baseline heart rate
      and heart rate variability (HRV), chronic alcohol use, and reasons for drinking.
      Two cluster groups were identified and labeled the high alcohol risk and
      normative groups. Compared to the normative group, individuals in the high
      alcohol risk group had higher levels of alcohol use and more strongly endorsed
      disinhibition and suppression reasons for use. The high alcohol risk group showed
      significant HRV changes in response to positive and negative emotional and
      appetitive picture cues, compared to neutral cues. In contrast, the normative
      group showed a significant HRV change only to negative cues. Findings suggest
      that individuals with autonomic self-regulatory difficulties may be more
      susceptible to heavy alcohol use and use of alcohol for emotional regulation.

PMID- 18331140
TI  - Cultural differences in the relationship between parenting and children's
      behavior.
AB  - Parent and teacher data for 14,990 children from the National Longitudinal Survey
      of Children and Youth were used in multilevel analyses to examine the
      relationship between ethnicity, children's aggression and emotional problems, and
      parenting. Using parent and teacher report, relationships between ethnicity and
      child behavior were present but modest. The association between parental
      harshness and child aggression differed between ethnic groups and across
      informants. Using teacher report of outcomes, parental harshness was positively
      related to child aggression in European Canadian families but negatively related
      in South Asian Canadian families. For all ethnic groups, parental harshness was
      positively related to children's aggression when parent report of outcomes was
      used, but relationships varied in strength across ethnic groups. The relationship
      of parental harshness with child emotional problems did not differ across groups,
      irrespective of informant. The results are discussed within the context of an
      ecological model of parenting.

PMID- 18331141
TI  - Theory of mind development in Chinese children: a meta-analysis of false-belief
      understanding across cultures and languages.
AB  - Theory of mind is claimed to develop universally among humans across cultures
      with vastly different folk psychologies. However, in the attempt to test and
      confirm a claim of universality, individual studies have been limited by small
      sample sizes, sample specificities, and an overwhelming focus on Anglo- European
      children. The current meta-analysis of children's false-belief performance
      provides the most comprehensive examination to date of theory-of-mind development
      in a population of non-Western children speaking non-Indo-European languages
      (i.e., Mandarin and Cantonese). The meta-analysis consisted of 196 Chinese
      conditions (127 from mainland China and 69 from Hong Kong), representing
      responses from more than 3,000 children, compared with 155 similar North American
      conditions (83 conditions from the United States and 72 conditions from Canada).
      The findings show parallel developmental trajectories of false-belief
      understanding for children in China and North America coupled with significant
      differences in the timing of development across communities-children's false
      belief performance varied across different locales by as much as 2 or more years.
      These data support the importance of both universal trajectories and specific
      experiential factors in the development of theory of mind.

PMID- 18331142
TI  - Stability and change in religiousness during emerging adulthood.
AB  - Understanding the development of religiousness is an important endeavor because
      religiousness has been shown to be related to positive outcomes. The current
      study examined mean-level, rank-order, and individual-level change in females'
      religiousness during emerging adulthood. Genetic and environmental influences on
      religiousness and its change and stability were also investigated. Analyses were
      completed with an epidemiological study of 2 cohorts of twins: 1 assessed at ages
      14 and 18 and a 2nd at 20 and 25. Mean levels of religiousness decreased
      significantly with age, while rank-order stability was high. Individual-level
      change was also evident. Analyses also supported the hypotheses that more change
      would occur in the younger cohort compared with the older cohort and that more
      change would occur in religious service attendance than the general index of
      religiousness. Twin analyses suggested that the heritability of religiousness
      increased with age, while the shared environmental influences decreased. For the
      younger cohort, change was genetic in origin, while stability was environmental.
      In the older cohort, change was influenced by nonshared environment and stability
      by both genes and family environment.

PMID- 18331143
TI  - The development of automatic numerosity processing in preschoolers: evidence for
      numerosity-perceptual interference.
AB  - Three experiments examined developmental changes in the automatic processing of
      numerosity and perceptual information using a nonsymbolic numerical Stroop
      paradigm. In Experiments 1 and 2 (E1 and E2), 4-, 5-, and 6-year-olds had to
      compare the numerosities or the total filled areas of collections of dots (E1) or
      bars (E2) varying along both dimensions. Experiment 3 replicated E2's results in
      3-, 4-, and 5-year-olds. Results demonstrated the existence of reciprocal
      influences between numerical and perceptual information beginning at age 3.
      Moreover, the irrelevant perceptual influences remained stable throughout
      development, whereas the sensitivity to irrelevant numerical cues tended to
      increase with age despite children's growing inhibition capacities. No
      significant correlation could be found between these developmental changes and
      the acquisition of counting knowledge.

PMID- 18331144
TI  - Infants' understanding of the link between visual perception and emotion: "If she
      can't see me doing it, she won't get angry.".
AB  - Two experiments investigated 18-month-olds' understanding of the link between
      visual perception and emotion. Infants watched an adult perform actions on
      objects. An emoter then expressed neutral affect or anger toward the adult in
      response to the adult's actions. Subsequently, infants were given 20 s to
      interact with each object. In Experiment 1, the emoter faced infants with a
      neutral expression during each 20-s response period but looked at either a
      magazine or the infant. In Experiment 2, the emoter faced infants with a neutral
      expression, and her eyes were either open or closed. When the emoter visually
      monitored infants' actions, the infants regulated their object-directed behavior
      on the basis of their memory of the emoter's affect. However, if the previously
      angry emoter read a magazine (Experiment 1) or closed her eyes (Experiment 2),
      infants were not governed by her prior emotion. Infants behaved as if they
      expected the emoter to get angry only if she could see them performing the
      actions. These findings suggest that infants appreciate how people's visual
      experiences influence their emotions and use this information to regulate their
      own behavior.

PMID- 18331145
TI  - Using confirmatory factor analysis to understand executive control in preschool
      children: I. Latent structure.
AB  - Although many tasks have been developed recently to study executive control in
      the preschool years, the constructs that underlie performance on these tasks are
      poorly understood. In particular, it is unclear whether executive control is
      composed of multiple, separable cognitive abilities (e.g., inhibition and working
      memory) or whether it is unitary in nature. A sample of 243 normally developing
      children between 2.3 and 6 years of age completed a battery of age-appropriate
      executive control tasks. Confirmatory factor analysis was used to compare
      multiple models of executive control empirically. A single-factor, general model
      was sufficient to account for the data. Furthermore, the fit of the unitary model
      was invariant across subgroups of children divided by socioeconomic status or
      sex. Girls displayed a higher level of latent executive control than boys, and
      children of higher and lower socioeconomic status did not differ in level. In
      typically developing preschool children, tasks conceptualized as indexes of
      working memory and inhibitory control in fact measured a single cognitive
      ability, despite surface differences between task characteristics.

PMID- 18331146
TI  - Number games, magnitude representation, and basic number skills in preschoolers.
AB  - The effect of 3 intervention board games (linear number, linear color, and
      nonlinear number) on young children's (mean age = 3.8 years) counting abilities,
      number naming, magnitude comprehension, accuracy in number-to-position estimation
      tasks, and best-fit numerical magnitude representations was examined. Pre- and
      posttest performance was compared following four 25-min intervention sessions.
      The linear number board game significantly improved children's performance in all
      posttest measures and facilitated a shift from a logarithmic to a linear
      representation of numerical magnitude, emphasizing the importance of spatial cues
      in estimation. Exposure to the number card games involving nonsymbolic magnitude
      judgments and association of symbolic and nonsymbolic quantities, but without any
      linear spatial cues, improved some aspects of children's basic number skills but
      not numerical estimation precision.

PMID- 18331147
TI  - Religious involvement and the social competence and adjustment of Indonesian
      Muslim adolescents.
AB  - This study assessed the relation between religious involvement and multiple
      indices of competence in 183 eighth- and ninth-grade Indonesian Muslim
      adolescents (M = 13.3 years). The authors assessed spirituality and religiosity
      using both parent and adolescent reports, and social competence and adjustment
      using multiple measures and data sources. Structural equation modeling analyses
      revealed that parent and adolescent reports of religiosity and spirituality
      yielded a single religious involvement latent variable that was related to peer
      group status, academic achievement, emotional regulation, prosocial behavior,
      antisocial/problem behavior, internalizing behavior, and self-esteem. The
      consistency of relations between religious involvement and competence may be in
      part attributable to the collectivist context of religion in West Java,
      Indonesia, within which people exhibit strong beliefs in Islam and religion
      permeates daily life.

PMID- 18331148
TI  - Complex prospective memory: development across the lifespan and the role of task
      interruption.
AB  - Prospective memory (PM) reflects the product of cognitive processes associated
      with the formation, retention, delayed initiation, and execution of intentions.
      It has been proposed that developmental changes in PM across the lifespan are
      heavily dependent upon the developmental trajectory of executive control
      functions. This study is the first to apply a complex PM task to children, young
      adults, and older adults. The procedure allows for the assessment of each of the
      4 phases of PM. During intention execution, the authors additionally manipulated
      whether participants had to actively interrupt attention to the current 'ongoing'
      task in order to switch to the execution of the next intended task. Group
      differences mirroring inverted U-shaped functions were observed in those phases
      conceptualized as relying on executive control (intention formation, initiation,
      and execution). Age differences in intention execution were substantially greater
      when active task interruption was necessary. The current study provides the first
      evidence of growth and decline of complex PM across the lifespan and suggests
      that the degree of inhibitory control needed to succeed in the task may be one
      factor underlying this development.

PMID- 18331149
TI  - Infant attention to intentional action predicts preschool theory of mind.
AB  - This research examines whether there are continuities between infant social
      attention and later theory of mind. Forty-five children were studied as infants
      and then again as 4-year-olds. Measures of infant social attention (decrement of
      attention during habituation to displays of intentional action) significantly
      predicted later theory of mind (false-belief understanding). Possibly, this
      longitudinal association could have been explained by more general developments
      in IQ, verbal competence, or executive function (rather than continuities in the
      realm of social cognition). However, the association remained significant and
      undiminished even when IQ, verbal competence, and executive function were
      controlled. The findings thus provide strong support for an important continuity
      in social cognition separable from continuities in more general information
      processing.

PMID- 18331150
TI  - Cluster randomized trials with treatment noncompliance.
AB  - Cluster randomized trials (CRTs) have been widely used in field experiments
      treating a cluster of individuals as the unit of randomization. This study
      focused particularly on situations where CRTs are accompanied by a common
      complication, namely, treatment noncompliance or, more generally, intervention
      nonadherence. In CRTs, compliance may be related not only to individual
      characteristics but also to the environment of clusters individuals belong to.
      Therefore, analyses ignoring the connection between compliance and clustering may
      not provide valid results. Although randomized field experiments often suffer
      from both noncompliance and clustering of the data, these features have been
      studied as separate rather than concurrent problems. On the basis of Monte Carlo
      simulations, this study demonstrated how clustering and noncompliance may affect
      statistical inferences and how these two complications can be accounted for
      simultaneously. In particular, the effect of the intervention on individuals who
      not only were assigned to active intervention but also abided by this
      intervention assignment (complier average causal effect) was the focus. For
      estimation of intervention effects considering noncompliance and data clustering,
      an ML-EM estimation method was employed.

PMID- 18331151
TI  - A probability-based measure of effect size: robustness to base rates and other
      factors.
AB  - Calculating and reporting appropriate measures of effect size are becoming
      standard practice in psychological research. One of the most common scenarios
      encountered involves the comparison of 2 groups, which includes research designs
      that are experimental (e.g., random assignment to treatment vs. placebo
      conditions) and nonexperimental (e.g., testing for gender differences). Familiar
      measures such as the standardized mean difference (d) or the point-biserial
      correlation (rpb) characterize the magnitude of the difference between groups,
      but these effect size measures are sensitive to a number of additional
      influences. For example, R. E. McGrath and G. J. Meyer (2006) showed that rpb is
      sensitive to sample base rates, and extending their analysis to situations of
      unequal variances reveals that d is, too. The probability-based measure A, the
      nonparametric generalization of what K. O. McGraw and S. P. Wong (1992) called
      the common language effect size statistic, is insensitive to base rates and more
      robust to several other factors (e.g., extreme scores, nonlinear
      transformations). In addition to its excellent generalizability across contexts,
      A is easy to understand and can be obtained from standard computer output or
      through simple hand calculations.

PMID- 18331152
TI  - Confidence intervals for the overall effect size in random-effects meta-analysis.
AB  - One of the main objectives in meta-analysis is to estimate the overall effect
      size by calculating a confidence interval (CI). The usual procedure consists of
      assuming a standard normal distribution and a sampling variance defined as the
      inverse of the sum of the estimated weights of the effect sizes. But this
      procedure does not take into account the uncertainty due to the fact that the
      heterogeneity variance (tau2) and the within-study variances have to be
      estimated, leading to CIs that are too narrow with the consequence that the
      actual coverage probability is smaller than the nominal confidence level. In this
      article, the performances of 3 alternatives to the standard CI procedure are
      examined under a random-effects model and 8 different tau2 estimators to estimate
      the weights: the t distribution CI, the weighted variance CI (with an improved
      variance), and the quantile approximation method (recently proposed). The results
      of a Monte Carlo simulation showed that the weighted variance CI outperformed the
      other methods regardless of the tau2 estimator, the value of tau2, the number of
      studies, and the sample size.

PMID- 18331153
TI  - On the meaning of the latent variables in the CT-C(M-1) model: a comment on
      Maydeu-Olivares and Coffman (2006).
AB  - In a recent article, A. Maydeu-Olivares and D. L. Coffman (2006) presented a
      random intercept factor approach for modeling idiosyncratic response styles in
      questionnaire data and compared this approach with competing confirmatory factor
      analysis models. Among the competing models was the CT-C(M-1) model (M. Eid,
      2000). In an application to the Life Orientation Test (M. F. Scheier & C. S.
      Carver, 1985), Maydeu-Olivares and Coffman found that results obtained from the
      CT-C(M-1) model were difficult to interpret. In particular, Maydeu-Olivares and
      Coffman challenged the asymmetry of the CT-C(M-1) model. In the present article,
      the authors show that the difficulties faced by Maydeu-Olivares and Coffman rest
      upon an improper interpretation of the meaning of the latent factors. The
      authors' aim is to clarify the meaning of the latent variables in the CT-C(M-1)
      model. The authors explain how to properly interpret the results from this model
      and introduce an alternative restricted model that is conceptually similar to the
      CT-C(M-1) model and nested within it. The fit of this model is invariant across
      different reference methods. Finally, the authors provide guidelines as to which
      model should be used in which research context.

PMID- 18331154
TI  - Testing intergroup concordance in ranking experiments with two groups of judges.
AB  - Across many areas of psychology, concordance is commonly used to measure the
      (intragroup) agreement in ranking a number of items by a group of judges.
      Sometimes, however, the judges come from multiple groups, and in those
      situations, the interest is to measure the concordance between groups, under the
      assumption that there is some within-group concordance. In this investigation,
      existing methods are compared under a variety of scenarios. Permutation theory is
      used to calculate the error rates and the power of the methods. Missing data
      situations are also studied. The results indicate that the performance of the
      methods depend on (a) the number of items to be ranked, (b) the level of within
      group agreement, and (c) the level of between-group agreement. Overall, using the
      actual ranks of the items gives better results than using the pairwise comparison
      of rankings. Missing data lead to loss in statistical power, and in some cases,
      the loss is substantial. The degree of power loss depends on the missing
      mechanism and the method of imputing the missing data, among other factors.

PMID- 18331156
TI  - Identical neural risk factors predict cognitive deficit in dyslexia and
      schizophrenia.
AB  - In previous work, the authors found that an anatomical risk index created from
      the combination of 7 neuroanatomical measures predicted reading and oral language
      skills in individuals with learning disabilities. Individuals with small auditory
      brain structures and reduced asymmetry had more deficits than those with large
      structures and exaggerated asymmetry. In the present study, the same anatomical
      index predicted reading and other cognitive abilities in 45 individuals with
      chronic schizophrenia. The anatomical risk index was significantly associated
      with broad cognitive ability (Pearson r = .53, p < .0001), reading comprehension
      (r = .58, p < .0001), and a measure of nonverbal reasoning (r = .39, p < .01),
      but not with age, parental socioeconomic status, symptom measures, alcohol use,
      or processing speed. These findings support the prediction that reduced size and
      asymmetry in temporal lobe auditory cortex and cerebellum may not be specific
      risk factors for schizophrenia but for cognitive deficits that characterize a
      broad spectrum of developmental disorders.

PMID- 18331158
TI  - Core neurocognitive functions in children treated for posterior fossa tumors.
AB  - Identifying cognitive deficits associated with pediatric brain tumors and their
      treatment is important in delineating the mechanisms of intellectual decline
      often associated with these diseases. The authors evaluated sustained attention,
      information processing speed, working memory, and IQ in 64 patients with
      posterior fossa tumors, including those treated with either: (a) surgery and
      cranial radiation (n = 32), and (b) surgery without radiation (n = 32). Ten
      patients treated for non-CNS solid tumors were included as a comparison group.
      The authors also examined the impact of relevant demographic and medical
      variables on neurocognitive outcome. The authors found that neither age at, nor
      time since, diagnosis predicted cognitive outcome in this sample. Further,
      sustained attention and working memory were largely intact and there were no
      differences between groups. Patients treated with cranial radiation demonstrated
      lowered short-form IQ and slow information processing speed: Patients treated
      with cranial radiation and who experienced postsurgical complications
      demonstrated the poorest performance. The authors consider information processing
      speed to be an excellent candidate mechanism in understanding the impact of
      cranial radiation on intellectual outcome.

PMID- 18331159
TI  - Object-based inhibition of return in patients with posterior parietal damage.
AB  - Recent evidence has shown that inhibition of return, IOR, is impaired in patients
      with parietal damage with or without clinical signs of neglect (Bartolomeo,
      Sieroff, Decaix, & Chokron, 2001; Vivas, Humphreys, & Fuentes, 2003,
      respectively). In addition to environment-based IOR, Tipper et al. (1991) showed
      that IOR could be also associated with dynamic, object-based representations. In
      our study, we examined four patients with unilateral lesions to the parietal
      lobe, and a group of healthy controls, in an IOR procedure with moving objects
      where a pre-cued object could move, clockwise or counterclockwise, 90 degrees in
      polar coordinates. The group of control participants showed a small but
      significant object-based IOR effect. In contrast, the patients showed an object
      based IOR effect when the objects moved from the contralesional field toward the
      ipsilesional field, whereas there was no IOR effect when they moved from the
      ipsilesional to the contralesional field. These findings are discussed in terms
      of the role of the parietal cortex in implementing attentional biases in both
      environment-based (Vivas et al., 2003) and object-based frames of reference.

PMID- 18331160
TI  - Recollection- and familiarity-based memory in healthy aging and amnestic mild
      cognitive impairment.
AB  - Little is known about the cognitive mechanisms of the memory impairment
      associated with amnestic mild cognitive impairment (aMCI). We explored
      recollection and familiarity in 27 healthy young adults, 45 healthy older adults,
      and 17 individuals with aMCI. Relative to the younger adults, recollection was
      reduced in the older adults, especially among those with aMCI. Familiarity did
      not differ among groups. In the healthy younger and older adults, better
      performance on a set of clinical memory measures that are sensitive to medial
      temporal lobe functioning was associated with greater recollection. In addition,
      among the healthy older adults better executive functioning was also associated
      with greater recollection. These results are consistent with the notion that
      recollection is a product of strategic processes mediated by the prefrontal
      cortex that suppport the retrieval of context-dependent memories from the
      hippocampus. Hippocampal atrophy associated with aMCI may disrupt this brain
      network, and thereby interfere with recollection.

PMID- 18331161
TI  - Comprehension of grammatical and emotional prosody is impaired in Alzheimer's
      disease.
AB  - Previous research has demonstrated impairment in comprehension of emotional
      prosody in individuals diagnosed with Alzheimer's disease (AD). The present pilot
      study further explored the prosodic processing impairment in AD, aiming to extend
      our knowledge to encompass both grammatical and emotional prosody processing. As
      expected, impairments were seen in emotional prosody. AD individuals were also
      found to be impaired in detecting sentence modality, suggesting that impairments
      in affective prosody processing in AD may be ascribed to a more general prosodic
      processing impairment, specifically in comprehending prosodic information
      signaled across the sentence level. AD participants were at a very mild stage of
      the disease, suggesting that prosody impairments occur early in the disease
      course.

PMID- 18331163
TI  - An investigation of working memory influences on lexical ambiguity resolution.
AB  - The present study employed a combined semantic judgment and lexical decision
      priming paradigm to examine the impact of working memory on the inhibitory
      processes of lexical ambiguity resolution. The results indicated that overall,
      participants activated one meaning of a presented homograph while not priming the
      alternative meaning. As hypothesized, participants with high working-memory spans
      exhibited a pattern of priming for congruent conditions and a lack of positive
      priming for incongruent conditions. In contrast, participants with low working
      memory capacity showed priming for both congruent and incongruent conditions, but
      only for conditions in which the context was related to the dominant meaning of
      the homograph. The results suggest that people with low working-memory capacity
      have difficulty inhibiting inappropriate homograph meanings and further
      demonstrate that these difficulties may vary as a function of context-meaning
      dominance.

PMID- 18331162
TI  - Delay discrimination and reversal eyeblink classical conditioning in abstinent
      chronic alcoholics.
AB  - Evidence has shown that alcoholism leads to volume reductions in brain regions
      critical for associative learning using the eyeblink classical conditioning
      paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment
      in simple forms of EBCC, whereas changes in forebrain structures result in
      impairment in more complex tasks. In this study, the ability of abstinent
      alcoholics and matched control participants to acquire learned responses during
      delay discrimination and discrimination reversal was examined and related to
      severity of drinking history and neuropsychological performance. During
      discrimination learning, one tone (CS+) predicted the occurrence of an airpuff
      (unconditioned stimulus), and another tone (CS-) served as a neutral stimulus;
      then the significance of the tones was reversed. Alcoholics who learned the
      initial discrimination were impaired in acquiring the new CS+ after the tones
      reversed; this is a function that has previously been linked to forebrain
      structures. It is suggested that a factor important to alcoholic addiction may be
      the presence of alcoholic-related associative responses that interfere with the
      ability to learn new more adaptive associations.

PMID- 18331164
TI  - Visual search performance in children rated as good or poor attenders: the
      differential impact of DAT1 genotype, IQ, and chronological age.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is characterized by poor
      attention to detail, poor attention maintenance, and variability throughout task
      performance. The authors used a quantitative trait loci approach to assess the
      association between the dopamine transporter (DAT1) high-risk genotype, cognitive
      performance (visual search and vigilance), and ADHD symptoms in a community
      sample of boys 6-11 years of age. The potential confounding effects of IQ and
      chronological age were also investigated. Results demonstrate that accuracy in
      target detection, not speed, distinguishes poor attenders from good attenders.
      The authors speculate that the measure of performance (e.g., time and false
      alarms) may be critical in detecting attentional weaknesses. In contrast, DAT1
      gene, known to be associated with the behavioral symptoms of ADHD, was unrelated
      to visual search or vigilance performance, although it was related to ADHD
      symptoms.

PMID- 18331165
TI  - Encoding and retrieval processes in velo-cardio-facial syndrome (VCFS).
AB  - Velo-cardio-facial syndrome (VCFS) is a neurogenetic disorder associated with
      very high risk for developing schizophrenia. More than half of affected
      individuals experience transient psychotic symptoms during childhood and a third
      may develop schizophrenia. Memory regulation deficits disturbing both the
      encoding and retrieval stages of memory represent core deficits in the cognitive
      profile associated with schizophrenia. In this study, the authors investigate
      memory regulation processes in 33 individuals with VCFS along with 33 age- and
      sex-matched control participants. By using a directed forgetting paradigm and a
      continuous recognition paradigm, the authors examined selective encoding and
      suppression of irrelevant contents during retrieval in VCFS. Group comparison
      analyses revealed comparable performances on selective encoding and recognition
      accuracy between the VCFS group and control group. However, individuals with VCFS
      were more likely to make false recognitions and showed deficits in the
      suppression of irrelevant contents. Results suggest that trait-like deficits of
      memory regulation in VCFS can be observed during the retrieval stage, while
      selective encoding remains efficient. Memory regulation processes during
      retrieval may constitute a trait deficit in the memory profile of individuals
      with VCFS and may contribute to the cognitive deficits underlying an increased
      risk for developing schizophrenia in this population.

PMID- 18331166
TI  - Coffee with jelly or unbuttered toast: commissions and omissions are dissociable
      aspects of everyday action impairment in Alzheimer's disease.
AB  - Relative to our understanding of the memory and language deficits associated with
      Alzheimer's disease (AD), little is known about problems with everyday action
      performance (i.e., meal preparation, grooming). The resource theory proposes that
      everyday action problems are best explained by a unitary deficit in general
      cognitive resources. However, recent research suggests that omission and
      commission errors may reflect dissociable aspects of action impairment, with only
      omissions associated with resource limitations. This study examined everyday
      action performance in 70 participants with AD who also underwent a
      neuropsychological evaluation. First, correlation and principal component
      analyses were performed to examine the construct(s) that might explain everyday
      action impairment. Second, relations between everyday task component(s) and
      neuropsychological tests were examined by using correlation and regression
      analyses. Third, differences in everyday action error patterns were examined
      among participants of comparable overall impairment levels. Results showed
      omission and commission errors were uncorrelated and distinct components of
      everyday action performance, predicted by different neuropsychological tests, and
      differentially distributed even among participants with comparable overall
      impairment.

PMID- 18331168
TI  - Differential effects of normal aging on recollection of concrete and abstract
      words.
AB  - Verbal memory is known to be affected by word features. Concrete words are
      remembered better than abstract words (concreteness effect), presumably due to
      the concurrent activation of image-based and/or semantic associations. Vivid
      remembering during recognition (recollection) has been linked to the hippocampus
      and is thought to be more affected by healthy aging than familiarity-based
      recognition. Recent evidence also implicated the hippocampus in the processing of
      concrete words. Based on these observations, we hypothesized age-related changes
      in recollection to affect concrete words more than abstract words. This
      prediction was tested in a cross-sectional design with three consecutive age
      groups (mean ages 21 years, 42 years, and 61 years). Changes in recollection, but
      not familiarity, across ages were significantly modulated by word concreteness.
      Recollection of concrete words showed a steady decline across age, while
      recollection of abstract words decreased only from young to middle age, leading
      to a reduced concreteness effect in the oldest group. These findings are
      consistent with the idea that changes in hippocampally mediated recollective
      processes during aging affect concrete words more than abstract words.

PMID- 18331167
TI  - Neuropsychological disturbance in schizophrenia: a diffusion tensor imaging
      study.
AB  - Patients with schizophrenia and healthy control subjects underwent both
      neuropsychological evaluation and magnetic resonance diffusion tensor imaging,
      during which the cingulum bundle (CB) and the uncinate fasciculus (UF) were
      defined with fiber tractography and their integrity was quantified. On the basis
      of prior findings, it was hypothesized that neuropsychological disturbance in
      schizophrenia may be characterized, in part, by 2 dissociable functional
      neuroanatomical relationships: (a) executive functioning-CB integrity and (b)
      episodic memory-UF integrity. In support of the hypothesis, hierarchical
      regression results indicated that reduced white matter of the CB and the UF
      differentially and specifically predicted deficits in executive functioning and
      memory, respectively. Neuropsychological correlates of the CB also extended to
      lower generalized intelligence, as well as to reduced visual memory that may be
      related to failures of contextual monitoring of to-be-remembered scenes. Reduced
      white matter of the CB and the UF may each make distinct contributions to
      neuropsychological disturbance in schizophrenia.

PMID- 18331169
TI  - Verbal and nonverbal memory processing in patients with obsessive-compulsive
      disorder: its relationship to clinical variables.
AB  - Memory deficits have been reported in several neuropsychological studies of
      obsessive-compulsive disorder (OCD). Dysfunction in nonverbal memory has been
      consistently reported, whereas findings on verbal memory are more heterogeneous.
      The authors studied 50 patients with OCD who were matched for sex, age,
      educational level, and hand dominance with 50 healthy controls (HC). Cognitive
      performance in both groups was assessed on verbal and nonverbal memory tasks, and
      several clinical variables were also assessed in the patient group. Patients with
      OCD showed a pattern of cognitive dysfunction with alterations in areas of
      nonverbal memory (recall and recognition), and verbal memory (learning and
      recall). Older age at onset of OCD was associated with poorer performance on
      verbal memory tasks. Low scores on some verbal memory tasks were associated with
      severity of OCD, and nonverbal memory was influenced by depressive symptoms. The
      study suggests the existence of dysfunction in the execution of verbal and
      nonverbal memory tasks in OCD; the influence of clinical variables depends on the
      specific neuropsychological function.

PMID- 18331170
TI  - Chance guessing in a forced-choice recognition task and the detection of
      malingering.
AB  - Guessing occurs on forced-choice (FC) tests for which responses cannot be based
      on relevant knowledge. Its importance is in inverse relation to the level of
      knowledge being measured, so that it becomes an increasing component of test
      scores as the level of knowledge decreases. It is also used as a benchmark to
      detect simulated impairment. This investigation examined the role of guessing in
      a 2-alternative FC face recognition test. Chance groups shown only the test items
      were asked to guess which were the targets, to measure the variation in scores
      likely to be found with pure guessing. Controls performed normally, and two
      simulation groups tried to fake amnesia. Results suggested that simple guessing
      in the chance group produced variable scores that overlapped both low genuine and
      "malingering" performance. Low control scores were hidden by the guessing "chance
      bonus," which ameliorated the apparent level of decline in memory. Simulators
      told of their role at the outset (before presentation of the target items)
      produced more convincing "amnesic" scores than those told only just before the
      test, who produced the expected below-chance level of score. It is suggested that
      guessing variability should be taken into account in interpreting FC scores.

PMID- 18331171
TI  - Procedural memory system supports single cue trace eyeblink conditioning in
      medial temporal lobe amnesia.
AB  - A number of studies investigating trace eyeblink conditioning have found
      impaired, but not eliminated, acquisition of conditioned responses (CRs) in both
      animals and humans with hippocampal removal or damage. The underlying mechanism
      of this residual learning is unclear. The present study investigated whether the
      impaired level of learning is the product of residual hippocampal function or
      whether it is mediated by another memory system that has been shown to function
      normally in delay eyeblink conditioning. Performance of bilateral medial temporal
      lobe amnesic patients who had a prior history of participating in eyeblink
      conditioning studies was compared to a control group with a similar training
      history and to an untrained control group in a series of single cue trace
      conditioning tasks with 500 ms, 250 ms, and 0 ms trace intervals. Overall,
      patients acquired CRs to a level similar to the untrained controls, but were
      significantly impaired compared to the trained controls. The pattern of
      acquisition suggests that amnesic patients may be relying on the expression of
      previously acquired, likely cerebellar based, procedural memory representations
      in trace conditioning.

PMID- 18331172
TI  - Have a surgical robot, why not provide cybersurgery?

PMID- 18331173
TI  - Deep brain stimulation boosts memory and invokes flashbacks.

PMID- 18331174
TI  - Insulin glargine and glulisine SoloSTAR pens for the treatment of diabetes.
AB  - Insulin is an effective medication for lowering hemoglobin A(1c) values and can
      be used for both basal and prandial coverage of hyperglycemia in Type 1 and Type
      2 diabetes. Despite its effectiveness there is still reluctance by patients and
      physicians to add insulin into the treatment regimen for Type 2 diabetes when
      needed. One of the key barriers to initiating insulin therapy is the method of
      delivery. Insulin delivery pens are continually developed as a means to improve
      upon the vial and syringe and to make it easier for patients to incorporate
      insulin therapy into their lifestyles. The SoloSTAR pen (Sanofi-Aventis, Paris,
      France) was developed to make insulin delivery easier and to help eliminate
      barriers to the initiation of insulin therapy. In this article, we discuss the
      features and characteristics of SoloSTAR that overcome existing unmet needs.

PMID- 18331175
TI  - Reductions in blood loss with a bipolar sealer in total hip arthroplasty.
AB  - Altogether, 50 primary total hip arthroplasties were performed in a prospective,
      blinded, randomized study comparing a bipolar sealer device to standard
      electrocautery for hemostasis. Cohorts were evaluated for intra- and
      postoperative blood loss, transfusion rate, hemoglobin levels and modified Harris
      hip scores. Variables such as age, gender and body mass index were correlated to
      transfusion requirements. Total blood loss in the bipolar sealer group was
      decreased by 40% and transfusions were reduced by 73%. There was a significant
      reduction in the intra- and postoperative blood loss, p = 0.002 and p = 0.001,
      respectively. There was no difference in clinical hip scores between groups. The
      bipolar sealer was an effective coagulation alternative for total hip
      arthroplasties, reducing blood loss and transfusion requirements without
      affecting outcome. It appears to reduce tissue damage and smoke production in
      comparison with standard electrocautery. These results were found even in
      patients with demographic characteristics associated with a higher risk of blood
      related complications.

PMID- 18331176
TI  - Inflatable penile prostheses for the treatment of erectile dysfunction: an
      update.
AB  - Male erectile dysfunction (ED) is a common medical condition. Three oral
      medications (sildenafil, vardenafil and tadalafil, all phosphodiesterase type 5
      inhibitors) have been developed and approved for the treatment of ED by the US
      FDA. Extensive worldwide marketing of these medications has raised public
      awareness of ED, and allowed many previously untreated men to seek and receive
      effective therapy. A variety of other ED treatments are available and approved by
      the FDA, including vacuum-constriction devices and intracavernous or
      intraurethral alprostadil. However, roughly 30-40% of men with ED are not
      adequately served by these treatments due to their cost, side effects,
      contraindications, the need to 'time' sexual activity, or lack of satisfactory
      erectile response. For men who do not respond to less invasive therapy, an
      inflatable penile prosthesis can provide a satisfying and effective alternative.
      This article will review and critique the inflatable penile prostheses that are
      currently available in the USA and the EU for the treatment of ED.

PMID- 18331177
TI  - Technical advances in urological laparoscopic surgery.
AB  - Advances in laparoscopic techniques, technology and instruments have changed the
      face of urology to the extent that the laparoscopic approach has become the
      standard of care for many common urological procedures. The future of laparoscopy
      will build on incorporating additional technological innovations to improve
      surgical outcomes, advance surgical techniques and thereby decrease perioperative
      morbidity. Developments in laparoscopic imaging, laparoscopic instrumentation and
      novel surgical techniques will offer advantages to patients and urologists in the
      future.

PMID- 18331178
TI  - Advances in endovascular interventions for deep vein thrombosis.
AB  - Deep vein thrombosis (DVT) can lead to significant clinical sequelae resulting in
      negative impact on patients' lifestyle. Clinical consequences of DVT may include
      acute symptoms, such as limb swelling and pain or chronic symptoms, such as
      venous ulceration, due to post-thrombotic syndrome. An overwhelming DVT may lead
      to sudden death due to pulmonary embolism. Conventional treatment of DVT includes
      initial systemic anticoagulation with possible thrombus removal in symptomatic
      patients who fail medical therapy. Recent advances in endovascular technologies
      have led to the development of a variety of minimally invasive, catheter-based
      strategies to remove venous thrombus. These technologies utilize various
      mechanical principles, including catheter-directed thrombolytic infusion,
      rheolytic thrombectomy, mechanical fragmentation or ultrasound energy to remove
      intraluminal thrombus. The adjunctive role of thrombolytic agents in these
      mechanical thrombectomy devices has resulted in an augmented treatment modality
      in interventional management of iliofemoral DVT. This article reviews the current
      advances in this technology and discusses the techniques of percutaneous
      treatment strategies of venous thrombotic conditions.

PMID- 18331180
TI  - Infections of electrophysiologic cardiac devices.
AB  - Infections related to electrophysiologic cardiac device placement are increasing
      dramatically and are associated with adverse outcomes. With the US population
      aging and living longer, cardiac devices are utilized in an older population with
      significant comorbidities, making the threat from infectious complications
      significant. Electrophysiologic cardiac devices typically include an implanted
      pulse generator and an intravascular lead. Infection may occur at any component
      of the device, resulting in varied presentations. Bacteremia in cardiac device
      recipients may reflect primary generator pocket infection, or alternate sources
      of bacteremia may result in secondary hematogenous lead infection. This review
      focuses on the pathology, diagnosis, management and prevention of
      electrophysiologic cardiac device infections.

PMID- 18331179
TI  - Biological effects of dynamic shear stress in cardiovascular pathologies and
      devices.
AB  - Altered and highly dynamic shear stress conditions have been implicated in
      endothelial dysfunction leading to cardiovascular disease, and in thromboembolic
      complications in prosthetic cardiovascular devices. In addition to vascular
      damage, the pathological flow patterns characterizing cardiovascular pathologies
      and blood flow in prosthetic devices induce shear activation and damage to blood
      constituents. Investigation of the specific and accentuated effects of such flow
      induced perturbations on individual cell-types in vitro is critical for the
      optimization of device design, whereby specific design modifications can be made
      to minimize such perturbations. Such effects are also critical in understanding
      the development of cardiovascular disease. This review addresses limitations to
      replicate such dynamic flow conditions in vitro and also introduces the idea of
      modified in vitro devices, one of which is developed in the authors' laboratory,
      with dynamic capabilities to investigate the aforementioned effects in greater
      detail.

PMID- 18331181
TI  - Preventing secondary cataract and anterior capsule contraction by modification of
      intraocular lenses.
AB  - Advances in intraocular lens (IOL) design have led to the use of lenses with
      improved performance including tinting, asphericity, multifocality and
      accommodation. To maximize the visual performance of these IOLs, postoperative
      complications such as secondary cataracts and anterior capsule contraction must
      be prevented. Various types of secondary cataracts may occur, each associated
      with complex biological reactions. Different design configurations, including
      square-edge IOLs, have been used to prevent secondary cataracts and anterior
      capsule contraction, but these have not been successful in sufficiently
      eliminating these complications. We have found that surface modification of IOL
      surfaces chemically improves surface quality and is also useful in preventing
      secondary cataracts and anterior capsule contraction. The UV/ozone treatment that
      we used as a surface modification method is a simple and highly effective method
      with no safety issues regarding materials following treatment. The combination of
      square-edge design and surface modification may be able to completely eliminate
      these postoperative complications.

PMID- 18331182
TI  - Advances in technologies for laser-assisted in situ keratomileusis (LASIK)
      surgery.
AB  - Laser-assisted in situ keratomileusis (LASIK) has become the most widely used
      form of refractive surgery today. The objective of this surgical technique is to
      modify the anterior corneal shape by ablating tissue from the stroma by means of
      the excimer laser after creating a hinged corneal flap. This way, we are able to
      change the refractive status of the patient, providing better unaided vision.
      Continuous improvements in the original technique have made the surgical
      procedure safer, more accurate and repeatable. These progressions are due to the
      development of novel technologies that are the responsible for new surgical
      instrumentation, which makes the surgical procedure easier for the surgeon, and
      better excimer laser ablation algorithms, which increase the optical quality of
      the ablation and thus the safety of the vision correction procedure. This article
      aims to describe the more relevant advances in LASIK that have played an
      important role in the spread and popularity of this technique.

PMID- 18331183
TI  - Bone morphogenetic proteins in total hip arthroplasty, osteonecrosis and trauma
      surgery.
AB  - This review provides an overview of the use of bone morphogenetic proteins to
      enhance bone healing and bone graft incorporation in difficult defects created
      from failed total hip arthroplasties, osteonecrosis of the femoral head and
      trauma. Multiple publications have demonstrated that bone morphogenetic proteins
      are osteoinductive in preclinical trials (i.e., animal models); however, there is
      controversy and limited understanding of the use of this technology in orthopedic
      surgical practice. The question remains as to whether they are useful in
      difficult fractures, nonunions and large defects created from failed total hip
      arthroplasty or femoral head osteonecrosis. There might be a small risk for
      infection by the process of introducing foreign materials in a clinical
      situation, but this has not yet been realized to date. In addition, these
      materials offer an advantage in large defects where there is not enough
      transplantable material available from the host. We believe that the use of these
      materials will become more widespread with newer carriers, minimally invasive
      applications and diminished commercial costs.

PMID- 18331184
TI  - Bioimpedance measurements of human body composition: critical analysis and
      outlook.
AB  - Bioimpedance spectroscopy represents one of the largest emerging medical device
      technologies. The method is generally known as impedance spectroscopy and is an
      inexpensive, yet extremely powerful, analytical technique for studying the
      electrical properties of materials. Much of what we know about biological cells
      and tissues comes from use of this technique in vitro. Due to the high impedance
      of the cell membrane, current flow through the cell is frequency dependent and
      this allows the fluid volume inside versus outside the body's cells to be
      determined. The fluid outside the cells is primarily related to fluid volume
      status while the intracellular fluid also relates to the body's cellular mass.
      Technical advances have removed much of the method's basic complexities. The
      first commercial bioimpedance spectroscopy device for in vivo human body
      composition studies was introduced in 1990. Major strides have been made and the
      method is now poised to enter mainstream clinical medicine but the field is only
      in its infancy. This paper attempts to fully describe the current use of
      impedance in the body composition field.

PMID- 18331186
TI  - Information processing models of cognition.

PMID- 18331185
TI  - Methionine metabolism and liver disease.
AB  - In the early 1930s, Banting and Best, the discoverers of insulin, found that
      choline could prevent the development of fatty liver disease (steatosis) in
      pancreatectomized dogs treated with insulin. Later work indicated that in rats
      and mice, diets deficient in labile methyl groups (choline, methionine, betaine,
      folate) produced fatty liver and that long-term administration of diets deficient
      in choline and methionine also caused hepatocellular carcinoma. These experiments
      not only linked steatosis and diabetes but also provided evidence, for the first
      time, of the importance of labile methyl group balance to maintain normal liver
      function. This conclusion is now amply supported by the observation of mice
      devoid of key enzymes of methionine and folate metabolism and in patients with
      severe deficiencies in these enzymes. Moreover, treatments with various
      methionine metabolites in experimental animal models of liver disease show
      hepatoprotective properties.

PMID- 18331187
TI  - Invariants of human behavior.

PMID- 18331188
TI  - Evolving homogeneous neurocontrollers for a group of heterogeneous robots:
      coordinated motion, cooperation, and acoustic communication.
AB  - This article describes a simulation model in which artificial evolution is used
      to design homogeneous control structures and adaptive communication protocols for
      a group of three autonomous simulated robots. The agents are required to
      cooperate in order to approach a light source while avoiding collisions. The
      robots are morphologically different: Two of them are equipped with infrared
      sensors, one with light sensors. Thus, the two morphologically identical robots
      should take care of obstacle avoidance; the other one should take care of
      phototaxis. Since all of the agents can emit and perceive sound, the group's
      coordination of actions is based on acoustic communication. The results of this
      study are a proof of concept: They show that dynamic artificial neural networks
      can be successfully synthesized by artificial evolution to design the neural
      mechanisms required to underpin the behavioral strategies and adaptive
      communication capabilities demanded by this task. Postevaluation analyses unveil
      operational aspects of the best evolved behavior. Our results suggest that the
      building blocks and the evolutionary machinery detailed in the article should be
      considered in future research work dealing with the design of homogeneous
      controllers for groups of heterogeneous cooperating and communicating robots.

PMID- 18331189
TI  - V-like formations in flocks of artificial birds.
AB  - We consider flocks of artificial birds and study the emergence of V-like
      formations during flight. We introduce a small set of fully distributed
      positioning rules to guide the birds' movements and demonstrate, by means of
      simulations, that they tend to lead to stabilization into several of the well
      known V-like formations that have been observed in nature. We also provide
      quantitative indicators that we believe are closely related to achieving V-like
      formations, and study their behavior over a large set of independent simulations.

PMID- 18331190
TI  - Metabolic photofragmentation kinetics for a minimal protocell: rate-limiting
      factors, efficiency, and implications for evolution.
AB  - A key requirement of an autonomous self-replicating molecular machine, a
      protocell, is the ability to digest resources and turn them into building blocks.
      Thus a protocell needs a set of metabolic processes fueled by external free
      energy in the form of available chemical redox potential or light. We introduce
      and investigate a minimal photodriven metabolic system, which is based on
      photofragmentation of resource molecules catalyzed by genetic molecules. We
      represent and analyze the full metabolic set of reaction-kinetic equations and,
      through a set of approximations, simplify the reaction kinetics so that
      analytical expressions can be obtained for the building block production. The
      analytical approximations are compared with the full equation set and with
      corresponding experimental results to the extent they are available. It should be
      noted, however, that the proposed metabolic system has not been experimentally
      implemented, so this investigation is conducted to obtain a deeper understanding
      of its dynamics and perhaps to anticipate its limitations. We demonstrate that
      this type of minimal photodriven metabolic scheme is typically rate-limited by
      the front-end photoexcitation process, while its yield is determined by the
      genetic catalysis. We further predict that gene-catalyzed metabolic reactions can
      undergo evolutionary selection only for certain combinations of the involved
      reaction rates due to their intricate interactions. We finally discuss how the
      expected range of metabolic rates likely affects other key protocellular
      processes such as container growth and division as well as gene replication.

PMID- 18331191
TI  - Towards unconventional computing through simulated evolution: control of
      nonlinear media by a learning classifier system.
AB  - We propose that the behavior of nonlinear media can be controlled automatically
      through evolutionary learning. By extension, forms of unconventional computing
      (viz., massively parallel nonlinear computers) can be realized by such an
      approach. In this initial study a light-sensitive subexcitable Belousov
      Zhabotinsky reaction in which a checkerboard image, composed of cells of varying
      light intensity projected onto the surface of a thin silica gel impregnated with
      a catalyst and indicator, is controlled using a learning classifier system.
      Pulses of wave fragments are injected into the checkerboard grid, resulting in
      rich spatiotemporal behavior, and a learning classifier system is shown to be
      able to direct the fragments to an arbitrary position through dynamic control of
      the light intensity within each cell in both simulated and real chemical systems.
      Similarly, a learning classifier system is shown to be able to control the
      electrical stimulation of cultured neuronal networks so that they display
      elementary learning. Results indicate that the learned stimulation protocols
      identify seemingly fundamental properties of in vitro neuronal networks. Use of
      another learning scheme presented in the literature confirms that such
      fundamental behavioral characteristics of a given network must be considered in
      training experiments.

PMID- 18331197
TI  - Computing knock-out strategies in metabolic networks.
AB  - Given a metabolic network in terms of its metabolites and reactions, our goal is
      to efficiently compute the minimal knock-out sets of reactions required to block
      a given behavior. We describe an algorithm that improves the computation of these
      knock-out sets when the elementary modes (minimal functional subsystems) of the
      network are given. We also describe an algorithm that computes both the knock-out
      sets and the elementary modes containing the blocked reactions directly from the
      description of the network and whose worst-case computational complexity is
      better than the algorithms currently in use for these problems. Computational
      results are included.

PMID- 18331198
TI  - Pathway analysis of microarray data via regression.
AB  - Pathway analysis of microarray data evaluates gene expression profiles of a
      priori defined biological pathways in association with a phenotype of interest.
      We propose a unified pathway-analysis method that can be used for diverse
      phenotypes including binary, multiclass, continuous, count, rate, and censored
      survival phenotypes. The proposed method also allows covariate adjustments and
      correlation in the phenotype variable that is encountered in longitudinal,
      cluster-sampled, and paired designs. These are accomplished by combining the
      regression-based test statistic for each individual gene in a pathway of interest
      into a pathway-level test statistic. Applications of the proposed method are
      illustrated with two real pathway-analysis examples: one evaluating relapse
      associated gene expression involving a matched-pair binary phenotype in children
      with acute lymphoblastic leukemia; and the other investigating gene expression in
      breast cancer tissues in relation to patients' survival (a censored survival
      phenotype). Implementations for various phenotypes are available in R.
      Additionally, an Excel Add-in for a user-friendly interface is currently being
      developed.

PMID- 18331199
TI  - Mammalian heme peroxidases: from molecular mechanisms to health implications.
AB  - A marked increase in interest has occurred over the last few years in the role
      that mammalian heme peroxidase enzymes, primarily myeloperoxidase, eosinophil
      peroxidase, and lactoperoxidase, may play in both disease prevention and human
      pathologies. This increased interest has been sparked by developments in our
      understanding of polymorphisms that control the levels of these enzymes, a
      greater understanding of the basic chemistry and biochemistry of the oxidants
      formed by these species, the development of specific biomarkers that can be used
      in vivo to detect damage induced by these oxidants, the detection of active forms
      of these peroxidases at most, if not all, sites of inflammation, and a
      correlation between the levels of these enzymes and a number of major human
      pathologies. This article reviews recent developments in our understanding of the
      enzymology, chemistry, biochemistry and biologic roles of mammalian peroxidases
      and the oxidants that they generate, the potential role of these oxidants in
      human disease, and the use of the levels of these enzymes in disease prognosis.

PMID- 18331200
TI  - Opposite expression of the antioxidant heme oxygenase-1 in primary cells and
      tumor cells: regulation by interaction of USF-2 and Fra-1.
AB  - Heme oxygenase-1 is the rate-limiting enzyme for the degradation of the
      prooxidant heme. Previously, we showed that an E-box within the HO-1 promoter is
      crucial for the regulation of HO-1 expression in primary hepatocytes. Further to
      investigate the importance of this E-box, we determined the regulatory capacity
      of the E-box-binding factor USF-2 in primary cells in comparison with transformed
      cell lines. We found that HO-1 expression was inhibited by USF-2 in primary
      cells, whereas it was induced in tumor cell lines. Mutation of either the E-box
      or the AP-1 site within the HO-1 promoter only partially affected the USF
      dependent regulation. However, this regulation was dramatically reduced in tumor
      cells and completely abolished in primary cells transfected with an HO-1 promoter
      construct containing mutations in both the E-box and the AP-1 site, suggesting
      that AP-1 factors and USF-2 may act in a cooperative manner. Indeed, protein
      protein interaction studies revealed that USF proteins interacted with Fra-1.
      Further, the USF-dependent HO-1 promoter activity was not detectable with an USF
      2 mutant lacking residues of the USF-specific region (USR) or the transactivation
      domain encoded by exon 4. Together, these data suggest that USF-2 has opposite
      regulatory roles for HO-1 gene expression in primary cells and tumor cell lines.

PMID- 18331201
TI  - Oxidation of myofilament protein sulfhydryl groups reduces the contractile force
      and its Ca2+ sensitivity in human cardiomyocytes.
AB  - This study sought to characterize the relation between the oxidation of protein
      sulfhydryl (SH) groups and Ca2+-activated force production in the human
      myocardium. Triton-permeabilized left ventricular cardiomyocytes from donor
      hearts were exposed to an oxidative (2,2'-dithiodipyridine, DTDP) agent in vitro,
      and the changes in isometric force, its Ca2+ sensitivity, the cross-bridge
      sensitive rate constant of force redevelopment at saturating [Ca2+] (k(tr,max)),
      and protein SH oxidation were monitored. DTDP (0.1-10 mM for 2 min) oxidized the
      myocardial proteins and diminished the Ca2+-activated force with different
      concentration dependences (EC(50,SH) = 0.17 +/- 0.02 mM and EC(50,force) = 2.46
      +/- 0.22 mM; mean +/- SEM). The application of 2.5 mM DTDP decreased the maximal
      Ca2+-activated force (to 64%), its Ca2+ sensitivity (DeltapCa(50) = 0.22 +/-
      0.02), and the steepness of the Ca2+-force relation (n(Hill), from 2.01 +/- 0.08
      to 1.76 +/- 0.08). These changes were paralleled by reductions in the free SH
      content of the proteins (to 15%) and in k(tr,max) (to 75%). SH-specific labeling
      identified SH oxidation of myosin light chain 1 and actin at DTDP concentrations
      at which the changes in the contractile parameters occurred. Our data suggest
      that SH oxidation in selected myofilament proteins diminishes the Ca2+-activated
      force and its Ca2+ sensitivity through an impaired Ca2+ regulation of the actin
      myosin cycle in the human heart.

PMID- 18331203
TI  - How to evaluate blood substitutes for endothelial cell toxicity.
AB  - The most common and widely transplanted tissue worldwide is blood. But concerns
      about safety and adequacy of blood transfusion have fostered 20 years of research
      into blood substitutes such as oxygen carriers based on modified hemoglobin (Hb).
      Chemically modified or genetically engineered Hb developed as oxygen therapeutics
      are designed to restore blood volume and to correct oxygen deficit due to
      ischemia in a variety of clinical settings. Uncontrolled oxidative reactions
      mediated by large amounts of cell-free Hb and their reactions with various
      oxidant/antioxidant and cell signalling systems emerge as an important pathway of
      toxicity. Hemoglobin can react with oxygen and NO, leading to the production of
      reactive oxygen or nitrogen species. Inside the bloodstream, oxidized Hb and
      ROS/RNS are in direct contact with endothelial cells (EC). Thus, chain reactions
      may trigger molecular and cellular biology, causing oxidative stress-related
      pathologies. This editorial presents an overview of interactions between Hb
      (modified or not) and EC. We also propose a wide range of techniques and methods
      to assess oxidative stress and inflammation responses of EC after exposure to Hb.
      This editorial can serve as a guide to evaluate in vitro toxicity of new Hb
      molecules.

PMID- 18331202
TI  - Nitric oxide in the vasculature: where does it come from and where does it go? A
      quantitative perspective.
AB  - Nitric oxide (NO) affects two key aspects of O2 supply and demand: It regulates
      vascular tone and blood flow by activating soluble guanylate cyclase (sGC) in the
      vascular smooth muscle, and it controls mitochondrial O2 consumption by
      inhibiting cytochrome c oxidase. However, significant gaps exist in our
      quantitative understanding of the regulation of NO production in the vascular
      region. Large apparent discrepancies exist among the published reports that have
      analyzed the various pathways in terms of the perivascular NO concentration, the
      efficacy of NO in causing vasodilation (EC50), its efficacy in tissue respiration
      (IC50), and the paracrine and endocrine NO release. In this study, we review the
      NO literature, analyzing NO levels on various scales, identifying and analyzing
      the discrepancies in the reported data, and proposing hypotheses that can
      potentially reconcile these discrepancies. Resolving these issues is highly
      relevant to improving our understanding of vascular biology and to developing
      pharmaceutical agents that target NO pathways, such as vasodilating drugs.

PMID- 18331204
TI  - Trends in resistance to ciprofloxacin, cefazolin, and gentamicin in the treatment
      of bacterial keratitis.
AB  - PURPOSE: The aim of this study was to evaluate the microbial profile, resistance
      patterns, and antibiotic sensitivity of bacterial keratitis to three commonly
      used ocular antibiotics. METHODS: All cases of bacterial keratitis referred to
      the Massachusetts Eye and Ear Infirmary Microbiology Laboratory from two
      consecutive annual 10-month periods were reviewed. The bacterial profile and
      resistance to ciprofloxacin, cefazolin, and gentamicin was evaluated within the
      two intervals. RESULTS: Of the 485 cultures analyzed, 66.4% (322) were positive
      for bacterial isolates. Of these, 19.2% were polymicrobial, 87.5% were gram
      positive, and 12.5% were gram-negative. The most prevalent isolate was coagulase
      negative Staphylococcus (45.5%), followed by S. aureus (15.2%). The resistance
      patterns for gram-positive bacteria for ciprofloxacin for the first versus second
      time interval were 12% and 22% (P = 0.04) respectively, for cefazolin 13% and 23%
      (P = 0.04), and for gentamicin 4% and 7% (P = 0.36). The resistance patterns for
      gram-negative bacteria for ciprofloxacin, cefazolin, and gentamicin were not
      significantly different in the two tested time periods (all P > 0.05).
      CONCLUSIONS: There was increased resistance of gram-positive organisms to
      ciprofloxacin and cefazolin, but not gentamicin, in the two examined time
      periods. Increased resistance to these commonly used antibiotics emphasizes the
      need for close follow-up after initial empiric treatment, and maintaining a low
      threshold for selecting alternative therapy.

PMID- 18331205
TI  - Impact of high maternal hemoglobin at first antenatal visit on pregnancy
      outcomes: a cohort study.
AB  - AIM: To determine whether high maternal hemoglobin (Hb) at first antenatal visit
      is associated with adverse pregnancy outcomes. METHODS: A retrospective cohort
      study was conducted in 920 singleton pregnancies who started their antenatal
      booking in the first trimester (<or=14 weeks' gestation). Women with first-visit
      high Hb levels (>125 g/L) were matched 1:1 with those who had normal Hb values
      (110-124 g/L) according to age group and parity. Adverse pregnancy outcomes
      including preeclampsia, gestational diabetes mellitus (GDM), preterm delivery,
      low birth weight (LBW), and small for gestational age (SGA) infants between both
      groups were compared. RESULTS: Complete obstetric records of 426 and 448 women
      who had high and normal Hb levels, respectively, were studied. By uni- and
      multivariable analyses, women with high Hb levels had significantly higher rates
      of preeclampsia and GDM than those with normal Hb levels; their adjusted relative
      risks were 3.8 (95% confidence interval [CI]; 2.0, 7.1) and 3.3 (95% CI; 1.8,
      6.0), respectively. Rates of preterm delivery, low birth weight, and small for
      gestational age infants between the two groups were not significantly different.
      CONCLUSION: Our findings suggest that high Hb in the first trimester is
      associated with subsequent preeclampsia and GDM.

PMID- 18331206
TI  - Retrospective audit of outcome of regional anesthesia for delivery in women with
      thrombocytopenia.
AB  - Regional anesthesia for pain at delivery in the presence of maternal
      thrombocytopenia is a clinical dilemma. We reviewed 10,369 obstetric cases (12
      months) from our tertiary center. Generally, hemodilution of pregnancy does not
      result in thrombocyte counts of <150,000/mm(3) at delivery. A total of 166 births
      (1.6%) were recorded in women with thrombocytes <150,000/mm(3) at delivery.
      Parturients with >150,000/mm(3) at week 36 were separated post hoc (n=35; 21%)
      and the remaining parturients were divided as having <100,000/mm(3) (n=30; 18%)
      or 101,000-150,000/mm(3) (n=101; 60.5%). Epidural or spinal anesthesia was
      administered to 30% women with <100,000/mm(3) whereas 56% women with
      >101,000/mm(3) received these options (P=0.003). A total of 13.9% of parturients
      with trimester-long thrombocytopenia required blood products; 10/23 (43.5%)
      parturients undergoing cesarean section also required blood products (P=0.000).
      Four of six babies with Apgar scores of <or=7 at 1-min were born to women with
      platelets <100,000/mm(3) (P=0.009). There were no statistically significant
      differences in mean birth weights. Women with thrombocytes <150,000/mm(3) at
      birth but within the normal range at week 36 were more likely multiparas
      (P=0.001). We conclude that a difference in maternal and neonatal outcomes exists
      between mothers who were thrombocytopenic only at delivery compared to those with
      trimester-long thrombocytopenia, with the latter mothers and babies having more
      adverse events.

PMID- 18331207
TI  - Fetal electrocardiographic monitoring during labor in relation to cord blood
      levels of the brain-injury marker protein S-100.
AB  - BACKGROUND: Cord artery protein S-100 levels at birth are potential markers of
      brain damage after asphyxia. Our aim was to investigate if S-100 levels were
      elevated in neonates with indirect signs of asphyxia during birth. S-100 levels
      in cord blood were studied in relation to cardiotocography (CTG) and fetal
      electrocardiography (FECG) changes during birth and to acidemia in umbilical
      blood. MATERIAL AND METHODS: This case-control study was performed in parallel to
      a large randomized controlled trial (RCT) studying FECG at birth. Protein S-100
      samples were collected from 103 neonates at birth and related to the CTG and ECG
      changes during labor and to pH in umbilical blood. RESULTS: Protein S-100 was
      significantly higher in neonates with umbilical artery blood pH<or=7.05, compared
      to neonates with pH>7.05. Furthermore, neonates with preterminal CTG patterns
      showed increased S-100 levels compared to neonates with normal CTG. Neonates
      having significant CTG and ECG changes, leading to intervention according to
      clinical guidelines, showed significantly higher S-100 levels compared to
      neonates without such indication of intervention. CONCLUSION: A relation exists
      between S-100 in umbilical blood at birth, acidosis and pathological patterns in
      CTG and FECG during labor.

PMID- 18331208
TI  - Prenatal hypoxia preconditioning improves hypoxic ventilatory response and
      reduces mortality in neonatal rats.
AB  - OBJECTIVE: Severe hypoxia/ischemia is a major cause of neonatal cardiorespiratory
      dysfunction and mortality. We tested whether prenatal hypoxia preconditioning
      would augment hypoxic and hypercapnic ventilatory responses, and thereby reduce
      neonatal mortality. METHODS: Pregnant rats at 19 days' gestation were exposed to
      six episodes of intermittent hypoxia (10-min of 15% O(2) followed by 10-min of
      normoxia/episode, PPC), or room air (CON) per day until delivery. The ventilatory
      responses to 1 min of 10% O(2) and 10% CO(2), and 5 min of 5% O(2) were performed
      in anesthetized pups. The conscious pups were exposed to 5% O(2) for
      approximately 105 min, and their mortality and dry/wet weight of the lung and
      brain were evaluated. RESULTS: We found that augmented ventilatory responses to 1
      min of 10% O(2) and 10% CO(2) were similar in the two groups (P>0.05). In
      contrast, 5 min of 5% O(2) initially caused a ventilatory peak response followed
      by a decline that was markedly diminished (35%, P=0.013) by PPC. PPC also
      significantly decreased neonatal mortality by 22% (P=0.044) as compared with CON.
      CONCLUSION: We conclude that prenatal hypoxia preconditioning reduces neonatal
      mortality apparently by improving the severe hypoxic ventilatory response.

PMID- 18331209
TI  - Intraplacental choriocarcinoma with fetomaternal hemorrhage: a case study and
      literature review.

PMID- 18331212
TI  - The Qinghai-Tibet railway.

PMID- 18331216
TI  - Low-dose acetylsalicylic acid analog and acetazolamide for prevention of acute
      mountain sickness.
AB  - Analgesic drugs like acetylsalicylic acid, paracetamol, and ibuprofen are
      frequently used by subjects suffering from headache of acute mountain sickness
      (AMS). It is not clear if the effect is due to analgesia or prevention of AMS. We
      performed a randomized controlled clinical trial comparing a low dose of an
      acetylsalicylic acid analog, calcium carbasalate (380 mg /day), to placebo in a
      cohort of altitude-naive subjects attempting a fast climb of Mt. Kilimanjaro
      (5896 m). A third noncontrolled open arm was proposed-the usual recommended
      preventive treatment of acetazolamide 500 mg/day. Of 93 potential participants,
      44 chose prevention with acetazolamide, 18 refused participation, 15 received
      calcium carbasalate, and 16 received placebo. Mean age was 39 +/- 9 (SD) yr and
      15% were female. AMS was quantified by the Lake Louise Symptom Score and
      physician assessment. Calcium carbasalate at 380 mg/day did not have any
      preventive effect on AMS and did not have any effect on the prevalence and
      intensity of headache. Event rate of AMS in the pooled carbasalate-placebo group
      was 84% and 55% in the acetazolamide group. The number needed to treat (NNT) at
      500 mg/day of acetazolamide was 3. One subject on acetazolamide developed high
      altitude cerebral edema and was treated with dexamethasone, oxygen, and descent
      by evacuation. In conclusion, low-dose calcium carbasalate is not effective for
      prevention of AMS. In addition, these results corroborate the contention that in
      typical steep climbing profile settings, such as used by commercial enterprise on
      Mt. Kilimanjaro, acetazolamide 500 mg/day may not be sufficient to prevent AMS or
      to sufficiently reduce symptom intensity in almost half of subjects.

PMID- 18331217
TI  - Diabetic retinopathy at high altitude.
AB  - The objective of this study was to determine whether altitude hypoxia favors the
      development of diabetic retinopathy (DR) in healthy type 1 diabetic climbers with
      tight glycemia control. The retinas of 7 type 1 diabetic climbers with a history
      of stays at high altitude were studied through nonmydriatic chamber retinography
      (Ffo-CNM). The retinographies were performed before and after a 7,143 m peak
      expedition. One of the subjects presented evidence of DR prior to the ascent, in
      addition to a microhemorrhage afterward; the rest of the retinographies were
      normal. Fine glycemia management and adequate acclimatization are not the only
      cautions for diabetics going to altitude; an ophthalmologic exam beforehand is
      also recommended.

PMID- 18331218
TI  - Acute normobaric hypoxia stimulates erythropoietin release.
AB  - Investigations studying the secretion of EPO (erythropoietin) in response to
      acute hypoxia have produced mixed results. Further, the errors associated with
      the various methods used to determine EPO are not well documented. The purpose of
      the current study was to determine the EPO response of 17 trained male subjects
      to either an acute bout of normobaric hypoxia (Hy; n = 10) or normoxia (Con; n =
      7). A secondary aim was to determine the error associated with the measurement of
      EPO. After baseline tests, the treatment group (Hy) underwent a single bout of
      hypoxic exposure (F(I(O(2))) approximately 0.148; 3100 m) consisting of a 90-min
      rest period followed by a 30-min exercise phase (50% V(O)(2max)). Venous blood
      samples were drawn pre (0 min) and post (120 min) each test to assess changes in
      plasma EPO (DeltaEPO). The control (Con) group was subjected to the same general
      experimental design, but placed in a normoxic environment (F(I(O(2)))
      approximately 0.2093). The Hy group demonstrated a mean increase in EPO [19.3
      (4.4) vs. 24.1 (5.1) mU/mL], p < 0.04, post 120 min of normobaric hypoxia. The
      calculated technical error of measurement for EPO was 2.1 mU/mL (9.8%). It was
      concluded that an acute bout of hypoxia, has the capacity to elevate plasma EPO.
      This study also demonstrates that the increase in EPO accumulation was 2 times
      greater than the calculated measurement of error.

PMID- 18331219
TI  - Color vision in the tritan axis is predominantly affected at high altitude.
AB  - The purpose of this study was to evaluate color vision during high altitude
      mountain climbing by applying the Mollon-Reffin Minimalist test to 14 climbers,
      all of whom were participating in the expedition to Ama Dablam (6,812 m) in
      Nepal. Before leaving for Nepal (at 300 m), all 28 eyes showed normal color
      vision in all 3 axes. At 1,300 m, 100% of eyes showed normal color vision in the
      protan and deutan axes, while 25% showed minimally reduced color discrimination
      in the tritan axis. At 4,000 m, 100% showed normal deutan axis, 4% minimally
      reduced protan axis, and 72% minimally reduced tritan axis discrimination. At
      5,400 m 100% of eyes tested showed normal protan and deutan axis discrimination,
      while 75% showed minimally and 25% moderately reduced tritan axis discrimination.
      Back home at 300 m 3 days after return, 100% showed normal deutan, 4% minimally
      reduced protan, and 38% minimally reduced tritan axis discrimination. One year
      later, all eyes showed normal color vision in all three axes. Changes in tritan
      axis discrimination correlated well with increased heart rate (r = 0.69; p =
      0.0001) and decreased oxygen saturation (r = 0.71; p = 0.001) at high altitude.
      This study shows that the tritan color vision axis is predominantly affected at
      high altitude, but that this reduced color discrimination is transient.

PMID- 18331220
TI  - Effects of intermittent hypoxia training on exercise performance, hemodynamics,
      and ventilation in healthy senior men.
AB  - The efficacy and safety of intermittent hypoxia training (IHT) were investigated
      in healthy, 60- to 74-yr-old men. Fourteen men (Gr 1) who routinely exercised
      daily for 20 to 30 min were compared with 21 (Gr 2) who avoided exercise. Their
      submaximal work-load power values before the IHT training were 94 +/- 3.7 and 66
      +/- 3.1, respectively. Before and after 10 days of IHT, the ventilatory response
      to sustained hypoxia (SH; 12% O(2) for 10 min), work capacity (bicycle
      ergometer), and forearm cutaneous perfusion (laser Doppler) were determined.
      During SH, no negative electrocardiogram (ECG) changes were observed in either
      group, and the ventilatory response to SH was unaltered by IHT. In Gr 1, IHT
      (normobaric rebreathing for 5 min, final Sa(O(2)) = 85% to 86%, followed by 5 min
      normoxia, 4/day) produced no changes in hemodynamic indixes and work capacity. In
      Gr 2, IHT decreased blood pressure (BP) by 7.9 +/- 3.1 mmHg (p < 0.05) and
      increased submaximal work by 11.3% (p < 0.05) and anaerobic threshold by 12.7% (p
      < 0.05). The increase in HR and BP caused by a 55 W-work load was reduced by 5%
      and 6.5%, respectively (p < 0.05). Cutaneous perfusion increased by 0.06 +/- 0.04
      mL/min/100 g in Gr 1 and by 0.11 +/- 0.04 mL/min/100 g in Gr 2 (p < 0.05).
      Hyperemia recovery time increased significantly by 15.3 +/- 4.6 sec in Gr 1 and
      by 25.2 +/- 11.2 sec in Gr 2. Thus, healthy senior men well tolerate IHT as
      performed in this investigation. In untrained, healthy senior men, IHT had
      greater positive effects on hemodynamics, microvascular endothelial function, and
      work capacity.

PMID- 18331221
TI  - Carbohydrate ingestion improves oxygen delivery in acute hypoxia.
AB  - It is generally accepted that an increase in blood CO(2) increases ventilation.
      We also know that during carbohydrate metabolism a larger amount of CO(2) is
      produced than during metabolism of lipids or proteins. The aim of the present
      study was therefore to assess whether carbohydrate ingestion can increase CO(2)
      production enough to stimulate ventilation, which could in turn increase arterial
      oxygenation and alleviate the symptoms of hypoxia in a hypoxic environment.
      Fourteen subjects participated in two trials, which consisted of two normoxic and
      an acute hypoxic period (F(i(O(2))) = 12.86%). Following the first control
      normoxic period, the subjects ingested either a 10% water solution of sucrose
      (CHO; 4 kcal/kg body mass) or an equal volume of water (control). Hemoglobin
      saturation, heart rate, and ventilation parameters were monitored throughout the
      experiment. In contrast to the control trial, CO(2) production (V(CO(2)); L),
      ventilation (V; L/min), and heart rate were all significantly (p < 0.001)
      increased in the CHO trial during the second normoxic exposure; these parameters
      were also significantly elevated during the hypoxic exposure, as compared to the
      control trial. Carbohydrate ingestion 40 min prior to acute hypoxic exposure
      significantly (p < 0.001) improved hemoglobin saturation by 4%. The results
      suggest that ingestion of carbohydrates can improve arterial oxygenation during
      acute hypoxic exposure.

PMID- 18331222
TI  - Cobalt supplementation promotes hypoxic tolerance and facilitates acclimatization
      to hypobaric hypoxia in rat brain.
AB  - In the present study, we report the molecular mechanisms of action by cobalt in
      facilitating acclimatization to hypobaric hypoxia using male Sprague-Dawley rats
      as the model system. We determined hypoxic gasping time and survival time as a
      measure to assess the degree of tolerance of animals to hypobaric hypoxia by
      exposing the animals to an altitude of 10,668 m. Oral administration of cobalt
      chloride (12.5 mg Co/kg body weight, BW, for 7 days) increased gasping time and
      hypoxic survival time by 3 to 4 times compared to the control animals. This could
      be attributed to an increased expression and the DNA binding activity of hypoxia
      inducible transcriptional factor (HIF-1alpha) and its regulated genes, that is,
      erythropoietin (EPO), vascular endothelial growth factor (VEGF), glucose
      transporter-1 (Glut-1), and nitric oxide synthase (NOS) levels. This in turn
      leads to better oxygenation, oxygen delivery, glucose transport, and maintenance
      of vascular tone, respectively, under oxygen-limited conditions. This was further
      confirmed by lower levels of lactate dehydrogenase (LDH) activity and lactate in
      the brain of cobalt + hypoxia group compared with animals exposed to hypoxia.
      Glucose levels also increased after cobalt supplementation. The findings of the
      study provide a basis for the possible use of cobalt for facilitating
      acclimatization to hypoxia and other conditions involving oxygen deprivation.

PMID- 18331223
TI  - Hypoxic preconditioning increases skin oxygenation and viability but does not
      alter VEGF expression or vascular density.
AB  - Intermittent hypoxia is known to elicit adaptive changes that increase tissue
      oxygen delivery. We investigated the effects of intermittent hypoxic exposure
      (IHE) in normal skin (course study) and evaluated whether preoperative IHE
      preconditioning alleviates acute ischemic injury in skin flaps (flap study). For
      4 weeks, 55 rats were exposed to a daily IHE-session (6 hypoxic cycles, 9% O(2),
      6 to 10 min) separated by 3 min of reoxygenation (20.9% O(2)). The time course of
      intracutaneous PO(2) was measured at weekly intervals. VEGF/VEGF-receptor-mRNA
      and vascular density were measured in normal skin before and after 1, 2, 3, and 4
      weeks of the IHE course (20 rats). In 35 rats, skin flaps were elevated after IHE
      and similar studies were undertaken in samples from 3 flap areas at postoperative
      days 0.5, 2, and 4. Additionally, flap survival and cutaneous blood flow were
      quantitated. In normal skin, PO(2) was initially significantly decreased during
      the hypoxic cycles (PO(2) 4.1 +/- 1.5 mmHg). After 4 weeks of IHE, PO(2) (34.5 +/
      5.8 mmHg) was maintained even under hypoxic conditions. In flaps, IHE led to a
      2.6-fold increase in PO(2), increased flap survival (+ 19.4%, day 7), and blood
      flow (+ 19.1%, day 10) (p < 0.01). In neither study did IHE-preconditioning
      increase VEGF/VEGF-receptor-mRNA expression or vascular density. We conclude that
      (1) IHE induces pronounced hypoxia in the skin, but progressive adaptation occurs
      within 4 weeks, (2) preoperative IHE-preconditioning leads to significantly
      higher PO(2), blood flow, and tissue survival in ischemic skin flaps, and (3) the
      transient hypoxia induced by IHE does not alter expression of VEGF or its
      receptors nor does it trigger angiogenesis.

PMID- 18331224
TI  - Mountaineering fatalities on Denali.
AB  - Mount McKinley, or Denali, is the tallest mountain in North America and attracts
      over 1,000 climbers annually from around the world. Since Denali is located
      within a national park, the National Park Service (NPS) manages mountaineering
      activities and attempts to maintain a balance of an adventurous experience while
      promoting safety. We retrospectively reviewed the fatalities on Denali from 1903
      to 2006 to assist the NPS, medical personnel, and mountaineers improve safety and
      reduce fatalities on the mountain. Historical records and the NPS climber
      database were reviewed. Demographics, mechanisms, and circumstances surrounding
      each fatality were examined. Fatality rates and odds ratios for country of origin
      were calculated. From 1903 through the end of the 2006 climbing season, 96
      individuals died on Denali. The fatality rate is declining and is 3.08/1,000
      summit attempts. Of the 96 deaths, 92% were male, 51% occurred on the West
      Buttress route, and 45% were due to injuries sustained from falls. Sixty-one
      percent occurred on the descent and the largest number of deaths in 1 year
      occurred in 1992. Climbers from Asia had the highest odds of dying on the
      mountain. Fatalities were decreased by 53% after a NPS registration system was
      established in 1995. Although mountaineering remains a high-risk activity, safety
      on Denali is improving. Certain groups have a significantly higher chance of
      dying. Registration systems and screening methods provide ways to target at-risk
      groups and improve safety on high altitude mountains such as Denali.

PMID- 18331227
TI  - Editorial.

PMID- 18331228
TI  - Receptor for Advanced Glycation Endproducts (RAGE): a formidable force in the
      pathogenesis of the cardiovascular complications of diabetes & aging.
AB  - Unifying mechanisms for the consequences of aging and chronic diabetes are coming
      to light with the identification that common to both settings is the production
      and accumulation of the largely irreversible Advanced Glycation Endproducts
      (AGEs). AGEs impart multiple consequences in the tissues; a key means by which
      they exert maladaptive effects is via their interaction with and activation of
      their chief cell surface receptor, Receptor for AGE or RAGE. Although the time
      course, rate and extent of AGE generation and accumulation in diabetes and aging
      may be distinct, unifying outcomes of the ligand-RAGE interaction in the
      vasculature and heart are linked to upregulation of inflammatory and tissue
      destructive mechanisms. Consistent with these concepts, administration of the
      ligand-binding decoy of RAGE, soluble or sRAGE, suppresses early initiation and
      progression of atherosclerosis in diabetic mice; suppresses exaggerated
      neointimal expansion consequent to arterial injury; and mitigates the adverse
      impact of ischemia/reperfusion injury in the heart. Importantly, the RAGE ligand
      repertoire upregulated in these settings is not limited to AGEs. The key finding
      that RAGE was a multi-ligand receptor unified the concept that in diabetes and
      aging, innate and adaptive inflammatory mechanisms contribute to the pathogenesis
      of tissue injury. We conclude that antagonism of RAGE may reflect a novel and
      therapeutically logical and safe target in cardiovascular stress induced by aging
      and chronic diabetes.

PMID- 18331229
TI  - RAGE: a single receptor for several ligands and different cellular responses: the
      case of certain S100 proteins.
AB  - The S100 protein family comprises at least 25 members which, with the exception
      of S100G, act as Ca2+-sensor proteins that participate in Ca2+ signal
      transduction by interacting with target proteins thereby modifying their
      activities. S100 proteins are expressed in vertebrates exclusively, display a
      cell-specific distribution, and regulate a large variety of intracellular
      activities. Some S100 proteins are released by a non-classical pathway and exert
      regulatory effects on several cell types. The receptor for advanced glycation end
      products (RAGE) has been shown to transduce extracellular effects of S100B,
      S100A4, S100A6, S100A11, S100A12, S100A13 and S100P. However, some S100 proteins
      can signal by engaging RAGE as well as non-RAGE receptors. Immune cells (i.e.,
      monocytes/macrophages/microglia, neutrophils and lymphocytes), activated
      endothelial and vascular smooth muscle cells, neurons, astrocytes, chondrocytes
      and pancreatic tumor cells are the cell types reported to respond to certain S100
      proteins via RAGE engagement. In general, relatively high concentrations of S100
      proteins are required for activation of RAGE in responsive cells. S100B is unique
      in that it can engage RAGE in neurons at low and high concentrations with trophic
      and toxic effects, respectively, and S100A4 stimulates matrix metalloproteinase
      13 release from chondrocytes at nanomolar doses in a RAGE-mediated manner.
      Oligomerization of S100 proteins under the non-reducing, high-Ca2+ conditions
      found extracellularly appears to play a relevant role in RAGE activation, and
      binding of at least S100A12 and S100B results in RAGE oligomerization. Thus,
      S100/RAGE interactions might have important consequences during development and
      in tissue homeostasis as well as in inflammatory, degenerative and tumor
      processes.

PMID- 18331230
TI  - RAGE as a receptor of HMGB1 (Amphoterin): roles in health and disease.
AB  - HMGB1/Amphoterin is a ubiquitous, highly conserved DNA-binding protein that can
      be also released to the extracellular space by various cell types. Extracellular
      HMGB1 regulates migratory responses of several cell types through binding to RAGE
      that communicates with the cytoskeleton to regulate cell motility. HMGB1-induced
      cell signalling has been associated with mechanisms of several diseases,
      including cancer, sepsis, rheumatoid arthritis, stroke and atherosclerosis. This
      article reviews the evidence linking the functional roles of HMGB1 to RAGE
      signalling. Furthermore, we discuss the molecular and cellular mechanisms that
      may explain the roles of HMGB1/RAGE in diverse disease processes.

PMID- 18331231
TI  - RAGE: a potential target for Abeta-mediated cellular perturbation in Alzheimer's
      disease.
AB  - This review focuses on the current findings regarding interaction between amyloid
      beta peptide (Abeta) and receptor for advanced glycation endproducts (RAGE) and
      its roles in the pathogenesis of Alzheimer's disease (AD). As a ubiquitously
      expressed cell surface receptor, RAGE mediates the effects of Abeta on microglia,
      blood-brain barrier (BBB) and neurons through activating different signaling
      pathways. Data from autopsy brain tissues, in vitro cell cultures and transgenic
      mouse models suggest that Abeta-RAGE interaction exaggerates neuronal stress,
      accumulation of Abeta, impaired learning memory, and neuroinflammation. Blockade
      of RAGE protects against Abeta-mediated cellular perturbation. These findings may
      have an important therapeutic implication for neurodegenerative disorders
      relevant to AD.

PMID- 18331232
TI  - Receptor for AGE (RAGE): weaving tangled webs within the inflammatory response.
AB  - The family of RAGE ligands, including Advanced Glycation Endproducts (AGEs),
      S100/calgranulins, High Mobility Group Box-1 (HMGB1) and amyloid beta peptide
      (Abeta) and beta-sheet fibrils are highly enriched in immune and inflammatory
      foci. In parallel, upregulation of Receptor for AGE (RAGE) is noted in diverse
      forms of inflammation and autoimmunity, based on experiments examining human
      tissues as well as animal models. Indeed, prior to the demonstration that
      S100/calgranulins were signal transduction ligands of RAGE, these molecules were
      considered "biomarkers" of disease and disease activity in disorders such as
      colitis and arthritis. Premiere roles for RAGE in advancing cellular migration
      implicate this receptor in targeting immune cells to vulnerable foci. Once
      engaged, ligand-RAGE interaction in inflammatory and vascular cells amplifies
      upregulation of inflammatory cytokines, adhesion molecules and matrix
      metalloproteinases (MMPs). Discerning the primal versus chronic injury-provoking
      roles for this ligand-receptor interaction is a challenge in delineating the
      functions of the ligand/RAGE axis. As RAGE is expressed by many of the key cell
      types linked integrally to the immune response, we propose that the sites and
      time course of ligand-RAGE stimulation determine the phenotype produced by this
      axis. Ultimately, drawing the fine line between antagonism versus stimulation of
      the receptor in health and disease will depend on the full characterization of
      RAGE in repair versus injury.

PMID- 18331233
TI  - RAGE in diabetic nephropathy.
AB  - As is diabetes itself, diabetic angiopathy is a multi-factorial disease. Advanced
      glycation endproducts (AGE) cause vascular cell derangement characteristic of
      diabetes, and this is mainly mediated by their interaction with receptor for AGE
      (RAGE). When made diabetic, RAGE-overexpressing transgenic mice exhibited
      exacerbation of the indices of nephropathy, and this was prevented by the
      inhibition of AGE formation. On the other hand, RAGE-deficient animals showed
      amelioration of diabetic nephropathy. Accordingly, AGE and RAGE should be
      regarded as environmental and cellular accounts and as a potential therapeutic
      target for diabetic nephropathy. In effect, substances that inhibit the formation
      of AGE, break preformed AGE, change metabolic flows away from glycation,
      antagonize RAGE, and capture RAGE ligands have been proven as effective remedies
      against this life-threatening disease.

PMID- 18331234
TI  - RAGE and its ligands in retinal disease.
AB  - RAGE, the receptor for advanced glycation endproducts (AGEs), is a multiligand
      signal transduction receptor of the immunoglobulin superfamily of cell surface
      molecules that has been implicated in the pathogenesis of diabetic complications,
      neurodegenerative diseases, inflammatory disorders, and cancer. These diverse
      biologic disorders reflect the multiplicity of ligands capable of cellular
      interaction via RAGE that include, in addition to AGEs, amyloid-beta (Abeta)
      peptide, the S100/calgranulin family of proinflammatory cytokines, and
      amphoterin, a member of the High Mobility Group Box (HMGB) DNA-binding proteins.
      In the retina, RAGE expression is present in neural cells, the vasculature, and
      RPE cells, and it has also been detected in pathologic cellular retinal responses
      including epiretinal and neovascular membrane formation. Ligands for RAGE, in
      particular AGEs, have emerged as relevant to the pathogenesis of diabetic
      retinopathy and age-related macular disease. While the understanding of RAGE and
      its role in retinal dysfunction with aging, diabetes mellitus, and/or activation
      of pro-inflammatory pathways is less complete compared to other organ systems,
      increasing evidence indicates that RAGE can initiate and sustain significant
      cellular perturbations in the inner and outer retina. For these reasons,
      antagonism of RAGE interactions with its ligands may be a worthwhile therapeutic
      target in such seemingly disparate, visually threatening retinal diseases as
      diabetic retinopathy, age-related macular degeneration, and proliferative
      vitreoretinopathy.

PMID- 18331235
TI  - RAGE, diabetes, and the nervous system.
AB  - Longstanding diabetes mellitus targets kidney, retina, and blood vessels, but its
      impact upon the nervous system is another important source of disability.
      Diabetic peripheral neuropathy is a serious complication of inadequately treated
      diabetes leading to sensory loss, intractable neuropathic pain, loss of distal
      leg muscles, and impairment of balance and gait. Diabetes has been implicated as
      a cause of brain atrophy, white matter abnormalities, and cognitive impairment
      and a risk factor for dementia. Recent studies have incriminated advanced
      glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of
      diabetic nervous system complications. The availability of RAGE knockout mice and
      a competitive decoy for AGEs, soluble RAGE (sRAGE), has advanced our knowledge of
      the RAGE-mediated signalling pathways within the nervous system. They also
      provide hope for a future novel intervention for the prevention of diabetes
      associated neurological complications. This review will discuss current knowledge
      of diabetes- and RAGE-mediated neurodegeneration, involving the distal-most level
      of epidermal nerve fibers in skin, major peripheral nerve trunks, dorsal root
      ganglia, spinal cord, and brain.

PMID- 18331236
TI  - RAGE and RAGE ligands in cancer.
AB  - The receptor for advanced glycation end-products (RAGE) is a multifunctional
      receptor with multiple ligands that is known to play a key role in several
      diseases, including diabetes, arthritis, and Alzheimer's disease. Recent evidence
      indicates that this receptor also has an important role in cancer. RAGE ligands,
      which include the S100/calgranulins and high-mobility group box 1 (HMGB1)
      ligands, are expressed and secreted by cancer cells and are associated with
      increased metastasis and poorer outcomes in a wide variety of tumors. These
      ligands can interact in an autocrine manner to directly activate cancer cells and
      stimulate proliferation, invasion, chemoresistance, and metastasis. RAGE ligands
      derived from cancer cells can also influence a variety of important cell types
      within the tumor microenvironment, including fibroblasts, leukocytes, and
      vascular cells, leading to increased fibrosis, inflammation, and angiogenesis.
      Several of the cells in the tumor microenvironment also produce RAGE ligands.
      Most of the cancer-promoting effects of RAGE ligands are the result of their
      interaction with RAGE. However, these ligands also often have separate
      intracellular roles, and some may interact with other extracellular targets, so
      it is not currently possible to assign all of their effects to RAGE activation.
      Despite these complications, the bulk of the evidence supports the premise that
      the ligand-RAGE axis is an important target for therapeutic intervention in
      cancer.

PMID- 18331237
TI  - Hepatic fat and adenosine triphosphate measurement in overweight and obese adults
      using 1H and 31P magnetic resonance spectroscopy.
AB  - BACKGROUND/AIMS: Magnetic resonance spectroscopy (MRS) measures hepatic fat and
      adenosine triphosphate (ATP), but magnetic resonance studies are challenging in
      obese subjects. We aimed to evaluate the inter- and intrarater reliability and
      stability of hepatic fat and ATP measurements in a cohort of overweight and obese
      adults. METHODS: We measured hepatic fat and ATP using proton MRS ((1)H MRS) and
      phosphorus MRS ((31)P MRS) at baseline in adults enrolled in the Action for
      Health in Diabetes (Look AHEAD) clinical trial at one site. Using logistic
      regression, we determined factors associated with successful MRS data
      acquisition. We calculated the intra- and inter-rater reliability for hepatic fat
      and ATP based on 20 scans analysed twice by two readers. We also calculated the
      stability of these measures three times on five healthy volunteers. RESULTS: Of
      244 participants recruited into our ancillary study, 185 agreed to MRS. We
      obtained usable hepatic fat data from 151 (82%) and ATP data from 105 (58%).
      Obesity was the strongest predictor of failed data acquisition; every unit
      increase in the body mass index reduced the likelihood of successful fat data by
      11% and ATP data by 14%. The inter- and intrarater reliability were excellent for
      fat (intraclass correlation coefficient=0.99), but substantially more variable
      for ATP. Fat measures appeared relatively stable, but this was less true for ATP.
      CONCLUSIONS: Obesity can hinder (1)H and (31)P MRS data acquisition and
      subsequent analysis. This impact was greater for hepatic ATP than hepatic fat.

PMID- 18331238
TI  - Is the Cancer of the Liver Italian Program system an adequate weighting for
      survival of hepatocellular carcinoma? Evaluation of intrascore prognostic value
      among 36 subgroups.
AB  - BACKGROUND: The Cancer of the Liver Italian Program (CLIP) staging system for
      hepatocellular carcinoma (HCC) was subdivided into 36 subgroups. We aimed to
      validate the prognostic value of CLIP scoring. METHODS: This study included 3868
      HCC cases treated between 1986 and 2002. Survival and prognostic impact of all
      subgroups were analysed. RESULTS: In primary CLIP, comparisons of each score
      showed a significant difference (P<0.001) and exhibited a linear trend (P<0.001).
      A CLIP score of 0 was used as control group. Portal vein thrombosis, Child-Pugh
      B, alpha-fetoprotein (AFP) > or =400 ng/ml and multinodular with tumour extension
      < or =50% of the four subgroups with a CLIP score of 1 exhibited decreasing
      univariate hazard ratios and 95% confidence intervals, with values of 2.99 (2.05
      4.37), 2.39 (2.00-2.86), 1.66 (1.40-1.96) and 1.39 (1.18-1.63) respectively.
      Homogeneity in the same score was evaluated by comparing subgroup survival
      curves. For scores 1-5, 83.3% (5/6), 57.1% (16/28), 24.4% (11/45), 3.6% (1/28)
      and 16.7% (1/6) pairs of survival curves significantly differed, respectively,
      with decreasing linear trend (P<0.001). CONCLUSION: Different prognostic
      weighting of four predictive factors caused intrascore heterogeneity. Lower CLIP
      scores were associated with increased differences in intrascore. In conclusion,
      the CLIP staging scoring system is a reasonable ordinal scale, but the clinician
      must be aware of the heterogeneity of mortality risk within a given score.

PMID- 18331239
TI  - Intra-operative application of real-time tissue elastography for the diagnosis of
      liver tumours.
AB  - OBJECTIVE: Real-time tissue elastography (RTE) has made it possible to visualize
      tissue elasticity. The aim of this study was to evaluate the usefulness of RTE
      for the differential diagnosis of liver tumours during surgical exploration.
      METHODS: Fifty-five liver tumours in 44 patients were examined with RTE,
      concomitant with routine intra-operative ultrasonography. Elasticity images were
      classified into four types, from type A (even strain) to type D (no strain),
      according to the distribution and the degree of the strain contrasted with that
      of the surrounding liver [elasticity type of liver tumour (ETLT)]. We evaluated
      the consistency of the findings of RTE with the pathological diagnosis as a
      reference standard. RESULTS: All malignant lesions showed various degrees of
      strain reduction in the tumour tissue. Twenty-one of 22 hepatocellular carcinomas
      (HCCs) were classified as type B with a sensitivity of 95.5%, a specificity of
      90.9% and an accuracy of 92.7%, while all 24 metastatic adenocarcinomas were
      classified as either type C or type D with a sensitivity of 100%, a specificity
      of 80.6% and an accuracy of 89.1%. CONCLUSION: Application of RTE in surgical
      exploration provided significant information about the elasticity of liver
      tumours. RTE, using a new criterion, ETLT, enabled us to distinguish rather
      accurately between two common malignancies: HCC and metastatic adenocarcinoma.

PMID- 18331240
TI  - Occult hepatitis B virus infection in pregnant woman and its clinical
      implication.
AB  - BACKGROUND/AIMS: The objective of this study was to document the prevalence rate
      of occult hepatitis B virus (HBV) in healthy pregnant woman and the possibility
      of transmission to the foetus. METHODS: This study was performed prospectively
      with 202 healthy pregnant women. HBV-DNA testing was performed using two specific
      quantitative tests with two independent sets of sera and cord blood. DNA
      sequencing analysis was carried out to confirm the specificity of polymerase
      chain reaction (PCR) product of HBV-DNA testing. RESULTS: Eight of 202 (4%)
      individuals with the TaqMan PCR assay and 23 of 202 (11.4%) with the COBAS
      Amplicor HBV Monitor test were HBV-DNA positive. Six (3%) individuals were
      positive with both methods. Sequencing and genotyping analysis of HBV polymerase
      gene with sera of the 75th subject resulted in genotype C. HBV-DNA testing with
      four cord blood samples showed that all were HBV-DNA negative. CONCLUSION: Occult
      HBV infection shows a difference in prevalence rate depending on the test method
      but the existence has been confirmed by sequencing analysis. Our results also
      suggest that vertical transmission through the cord blood is not so high as to be
      clinical problems and warrants further investigation.

PMID- 18331241
TI  - A decision analysis study of the value of a liver biopsy in nonalcoholic
      steatohepatitis.
AB  - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent
      clinical syndrome reflecting a mixture of pathological liver histology with the
      potential to progress to cryptogenic cirrhosis. Liver biopsy (LB) is the only way
      to determine the severity of disease. However, LB is invasive, has complications
      and financial costs. The aim of this study is to determine the benefits of early
      LB for diagnosis and early treatment. METHODS: A decision tree model tracked the
      potential outcomes of NAFLD between an LB-directed approach vs. no initial LB.
      Each specific biopsy category determined subsequent care actions. The baseline
      probabilities were determined by literature review and expert opinion. RESULTS:
      An initial LB strategy was projected to have a lower mortality compared with the
      no initial LB group and fewer transplant eligible patients after 5 years. If the
      prevalence of NAFLD is increased, the mortality increases in both the study
      groups. With improved efficacy of medical and/or surgical intervention, the
      mortality rate was decreased. CONCLUSION: This decision tree model provides a
      context for balancing the risk and benefit of LB in NAFLD. With early biopsy, and
      early intervention, the relative return of preventing advanced liver disease per
      LB was high.

PMID- 18331242
TI  - The landscape genetics of yellow perch (Perca flavescens) in a large fluvial
      ecosystem.
AB  - Landscape genetics is being increasingly applied to elucidate the role of
      environmental features on the population structure of terrestrial organisms.
      However, the potential of this framework has been little explored in aquatic
      ecosystems such as large rivers. Here, we used a landscape genetics approach in
      order to (i) document the population structure of the yellow perch (Perca
      flavescens) by means of genetic variation at microsatellite markers, (ii) assess
      to what extent the structure was explained by landscape heterogeneity, and (iii)
      interpret the relevance of interactions between genetics and landscape for
      management and conservation. Analysis of the genetic variation among 1715
      individuals from 16 localities and distributed over 310 km in the freshwater
      section of the Saint Lawrence River (Quebec, Canada) revealed a relatively modest
      level of genetic structuring (F(ST) = 0.039). Application of the Monmonier's
      algorithm combining geographical and genetic information identified three zones
      of restricted gene flow defining four distinct populations. Physical barriers
      played a more important role on gene flow and genetic structure than waterway
      geographical distance. We found correlations between genetic differentiation and
      presence of distinct water masses in the sector of Lake Saint-Louis (r = 0.7177,
      P = 0.0340) and with fragmentation of spawning habitats in the sector of Lake
      Saint-Pierre (r = 0.8578, P = 0.0095). Our results support the treatment of four
      distinct biological units, which is in contrast with the current basis for yellow
      perch management. Finally, this study showed that landscape genetics is a
      powerful means to identify environmental barriers to gene flow causing genetic
      discontinuities in apparently highly connected aquatic landscapes.

PMID- 18331243
TI  - The seabird paradox: dispersal, genetic structure and population dynamics in a
      highly mobile, but philopatric albatross species.
AB  - The philopatric behaviour of albatrosses has intrigued biologists due to the high
      mobility of these seabirds. It is unknown how albatrosses maintain a system of
      fragmented populations without frequent dispersal movements, in spite of the long
      term temporal heterogeneity in resource distribution at sea. We used both genetic
      (amplified fragment length polymorphism) and capture-mark-recapture (CMR) data to
      identify explicitly which among several models of population dynamics best
      applies to the wandering albatross (Diomedea exulans) and to test for migration
      drift equilibrium. We previously documented an extremely low genetic diversity in
      this species. Here, we show that populations exhibit little genetic
      differentiation across the species' range (Theta(B) < 0.05, where Theta(B) is an
      F(ST) analogue). Furthermore, there was no evidence of hierarchical structure or
      isolation-by-distance. Wright's F(ST) between pairs of colonies were low in
      general and the pattern was consistent with a nonequilibrium genetic model. In
      contrast, CMR data collected over the last decades indicated that about one bird
      per cohort has dispersed among islands. Overall, F(ST) values were not indicative
      of contemporary dispersal as inferred from CMR data. Moreover, all genotypes
      grouped together in a cluster analysis, indicating that current colonies may have
      derived from one ancestral source that had a low genetic diversity. A
      metapopulation dynamics model including a recent (postglacial) colonization of
      several islands seems consistent with both the very low levels of genetic
      diversity and structure within the wandering albatross. Yet, our data suggest
      that several other factors including ongoing gene flow, recurrent long-distance
      dispersal and source-sink dynamics have contributed to different extent in
      shaping the genetic signature observed in this species. Our results show that an
      absence of genetic structuring may in itself reveal little about the true
      population dynamics in seabirds, but can provide insights into important
      processes when a comparison with other information, such as demographic data, is
      possible.

PMID- 18331244
TI  - A tale of two worlds: molecular ecology and population structure of the
      threatened Florida scrub-jay.
AB  - Elsewhere in this issue of Molecular Ecology, Coulon et al. provide a detailed
      analysis of population structure of the threatened Florida scrub-jay (Aphelocoma
      coerulescens) using genetic markers and compare it to that inferred from previous
      demographic surveys and observed dispersal behaviour in this species. In contrast
      to previous attempts at such comparisons, estimates from the two methods are
      reasonably congruent. Although challenges remain, Coulon et al.'s analyses
      demonstrate the potential for closing the gap between these alternative
      methodologies, and ultimately for future genetic surveys to be used confidently
      in conservation planning.

PMID- 18331245
TI  - Italy as a major Ice Age refuge area for the bat Myotis myotis (Chiroptera:
      Vespertilionidae) in Europe.
AB  - The distribution of biota from the temperate regions changed considerably during
      the climatic fluctuations of the Quaternary. This is especially true for many bat
      species that depend on warm roosts to install their nursery colonies. Surveys of
      genetic variation among European bats have shown that the southern peninsulas
      (Iberia and the Balkans) harbour endemic diversity, but to date, no such surveys
      have been conducted in the third potential glacial refuge area, the Apennine
      peninsula. We report here the phylogeographical analysis of 115 greater mouse
      eared bats (Myotis myotis) sampled throughout Italy, and show that 15 of the 18
      different haplotypes found in the mitochondrial control region of these bats were
      unique to the Apennine peninsula. Colonies within this region also showed
      substantial genetic structure at both mitochondrial (Phi(ST) = 0.47, P < 0.001)
      and nuclear markers (F(ST) = 0.039, P < 0.001). Based on a comprehensive survey
      of 575 bats from Europe, these genetic markers further indicate that central
      Italian populations of M. myotis are more closely related to Greek samples from
      across the Adriatic Sea, than to other Italian bats. Mouse-eared bat populations
      from the Apennine peninsula thus represent a complex mixture of several endemic
      lineages, which evolved in situ, with others that colonized this region more
      recently along an Adriatic route. Our broad survey also confirms that the Alps
      represent a relatively impermeable barrier to gene flow for Apennine lineages,
      even for vagile animals such as bats. These results underline the conservation
      value of bats from this region and the need to include the Apennine peninsula in
      phylogeographical surveys in order to provide a more accurate view of the
      evolution of bats in Europe.

PMID- 18331246
TI  - Small-scale spatial genetic structure in the Central African rainforest tree
      species Aucoumea klaineana: a stepwise approach to infer the impact of limited
      gene dispersal, population history and habitat fragmentation.
AB  - Under the isolation-by-distance model, the strength of spatial genetic structure
      (SGS) depends on seed and pollen dispersal and genetic drift, which in turn
      depends on local demographic structure. SGS can also be influenced by historical
      events such as admixture of differentiated gene pools. We analysed the fine-scale
      SGS in six populations of a pioneer tree species endemic to Central Africa,
      Aucoumea klaineana. To infer the impacts of limited gene dispersal, population
      history and habitat fragmentation on isolation by distance, we followed a
      stepwise approach consisting of a Bayesian clustering method to detect
      differentiated gene pools followed by the analysis of kinship-distance curves.
      Interestingly, despite considerable variation in density, the five populations
      situated under continuous forest cover displayed very similar extent of SGS. This
      is likely due to an increase in dispersal distance with decreased tree density.
      Admixture between two gene pools was detected in one of these five populations
      creating a distinctive pattern of SGS. In the last population sampled in open
      habitat, the genetic diversity was in the same range as in the other populations
      despite a recent habitat fragmentation. This result may due to the increase of
      gene dispersal compensating the effect of the disturbance as suggested by the
      reduced extent of SGS estimated in this population. Thus, in A. klaineana, the
      balance between drift and dispersal may facilitate the maintenance of genetic
      diversity. Finally, from the strength of the SGS and population density, an
      indirect estimate of gene dispersal distances was obtained for one site: the
      quadratic mean parent-offspring distance, sigma(g), ranged between 210 m and 570
      m.

PMID- 18331247
TI  - Bleaching and stress in coral reef ecosystems: hsp70 expression by the giant
      barrel sponge Xestospongia muta.
AB  - Sponges are a prominent component of coral reef ecosystems. Like reef-building
      corals, some sponges have been reported to bleach and die. The giant barrel
      sponge Xestospongia muta is one of the largest and most important components of
      Caribbean coral reef communities. Tissues of X. muta contain cyanobacterial
      symbionts of the Synechococcus group. Two types of bleaching have been described:
      cyclic bleaching, from which sponges recover, and fatal bleaching, which usually
      results in sponge death. We quantified hsp70 gene expression as an indicator of
      stress in X. muta undergoing cyclic and fatal bleaching and in response to
      thermal and salinity variability in both field and laboratory settings.
      Chlorophyll a content of sponge tissue was estimated to determine whether hsp70
      expression was related to cyanobacterial abundance. We found that fatally
      bleached sponge tissue presented significantly higher hsp70 gene expression, but
      cyclically bleached tissue did not, yet both cyclic and fatally bleached tissues
      had lower chlorophyll a concentrations than nonbleached tissue. These results
      corroborate field observations suggesting that cyclic bleaching is a temporary,
      nonstressful state, while fatal bleaching causes significant levels of stress,
      leading to mortality. Our results support the hypothesis that Synechococcus
      symbionts are commensals that provide no clear advantage to their sponge host. In
      laboratory experiments, sponge pieces incubated at 30 degrees C exhibited
      significantly higher hsp70 expression than control pieces after 1.5 h, with
      sponge mortality after less than 15 h. In contrast, sponges at different
      salinities were not significantly stressed after the same period of time. Stress
      associated with increasing seawater temperatures may result in declining sponge
      populations in coral reef ecosystems.

PMID- 18331248
TI  - Sensitization of Bacillus subtilis spores to dry heat and desiccation by
      pretreatment with oxidizing agents.
AB  - AIMS: To determine if pretreatment with oxidizing agents sensitizes Bacillus
      subtilis spores to dry heat or desiccation. METHODS: Bacillus subtilis spores
      were killed approx. 90% by oxidizing agents, and the sensitivity of treated and
      untreated spores to dry heat and desiccation was determined. The effects of
      pyruvate on spore recovery after oxidizing agent pretreatment and then dry heat
      or desiccation were also determined. CONCLUSIONS: Spores pretreated with Oxone or
      hypochlorite were not sensitized to dry heat or freeze-drying. However, hydrogen
      peroxide or t-butylhydroperoxide pretreatment sensitized spores to dry heat or
      desiccation, and the desiccation caused mutagenesis in the survivors. Pyruvate
      increased recovery of spores treated with hydrogen peroxide alone or plus dry
      heat or desiccation, and with t-butylhydroperoxide and desiccation, but not with
      t-butylhydroperoxide alone or plus dry heat. SIGNIFICANCE AND IMPACT OF THE
      STUDY: Pretreatment with peroxides sensitizes bacterial spores to subsequent
      stress. This finding may suggest improved regimens for spore inactivation.

PMID- 18331249
TI  - Is a 24 week treatment schedule with PegInterferon and Ribavirin too short for
      HCV genotype 3 cirrhotics?

PMID- 18331250
TI  - Fas / FasL system, IL-1beta expression and apoptosis in chronic HBV and HCV liver
      disease.
AB  - The Fas / Fas-ligand (FasL) system is an important death signal pathway in the
      liver. An enhanced local inflammatory response prompted by FasL expression, which
      contributes to neutrophil recruitment and interleukin-1 beta (IL-1beta) release,
      seems to be crucial to chronic liver damage, persistence of viral infections, and
      probably initiation and / or promotion of HCC. In order to evaluate the
      expression of Fas, FasL, and IL-1beta in different stages of human liver disease
      and to determine whether hepatitis B virus (HBV) and hepatitis C virus (HCV)
      infections modulate their expression, also in relation to apoptosis, we examined
      87 liver samples obtained from patients with: chronic hepatitis (CH) (n.42),
      cirrhosis (n.9) and hepatocellular carcinoma (HCC) (n.16) and corresponding
      peritumoural tissues (n.16); histologically-normal liver (n.4) as controls. Fas,
      FasL and IL-1beta mRNA were quantified using reverse transcriptase-polymerase
      chain reaction. The apoptotic index was evaluated by TUNEL analysis. Our data
      showed a progressive Fas / FasL increase from CH to cirrhosis followed by a
      decline from the latter to HCC. In histological sections apoptosis was detected
      in HCC. A significant difference emerged between HCV and HBV-related disease for
      IL-1beta expression only in CH. A significant positive correlation between IL
      1beta and FasL in HCV-related disease (P = 0.014) and an inverse correlation
      between IL-1beta and Fas in HBV-related disease (P = 0.021) were observed. The
      different pattern of IL-1beta, Fas and FasL expression found in HCV- and HBV
      mediated liver disease, points to a different modulation of immune response B and
      C virus induced, while the decline in Fas / FasL expression in HCC may be related
      to defence mechanisms adopted by HCC cells against the immune system.

PMID- 18331251
TI  - Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B
      and C.
AB  - 8-Hydroxydeoxyguanosine (8-OHdG) is a promutagenic DNA lesion produced by
      hydroxyl radicals and is recognized as a useful marker in estimating DNA damage
      induced by oxidative stress. The aim of this study was to clarify the clinical
      significance of hepatic 8-OHdG levels in patients with chronic viral hepatitis.
      Hepatic 8-OHdG accumulation was investigated in patients with chronic hepatitis C
      (CH-C) (n = 77) and chronic hepatitis B (CH-B) (n = 34) by immunohistochemical
      staining of liver biopsy samples. 8-OHdG positive hepatocytes were significantly
      higher in patients with CH-C compared to CH-B (median 55.0 vs 18.8 cells/10(5)
      mum(2), P < 0.0001). The number of positive hepatocytes significantly increased
      with the elevation of serum aminotransferase levels, especially in CH-C patients
      (8-OHdG vs alanine aminotransferase (ALT)/aspartate aminotrasferase (AST) were r
      = 0.738/0.720 in CH-C and 0.506/0.515 in CH-B). 8-OHdG reactivity was strongly
      correlated with body and hepatic iron storage markers in CH-C (vs serum ferritin,
      r = 0.615; vs hepatic total iron score, r = 0.520; vs hepatic hepcidin mRNA
      levels, r = 0.571), although it was related to serum HBV-DNA titers (r = 0.540)
      and age of patients (r = -0.559) in CH-B. These results indicate that hepatic
      oxidative DNA damage is common in chronic viral hepatitis, in particular chronic
      HCV-infected patients, suggesting a possible link between chronic hepatic
      inflammation and hepatocarcinogenesis. The strong positive correlation between
      hepatic DNA damage and iron overload suggests that iron content is one of the
      most likely mediators of hepatic oxidative stress and iron reduction may be
      beneficial to reduce the incidence of hepatic cancer in CH-C patients.

PMID- 18331252
TI  - An unusual staged labial rejuvenation.
AB  - INTRODUCTION: There have been concerns about the safety and effectiveness of
      publicized procedures in elective female genital rejuvenation. AIM: To present an
      interesting case in which a staged approach to rejuvenation of both the Labia
      majora and minora was performed safely and effectively. METHODS: A patient with
      an unusual redundancy of both the Labia minora and majora presented interested in
      reduction. The procedure was performed in two parts. RESULTS: Despite her
      complication following the first stage, 6 weeks after her second stage, the
      patient is satisfied. CONCLUSIONS: Cosmetic reduction of the Labia minora is well
      tolerated and can offer pleasing results with little morbidity. Surgery of the
      Labia majora may be more commonly complicated by bleeding.

PMID- 18331253
TI  - Normal variations in personality are associated with coital orgasmic infrequency
      in heterosexual women: a population-based study.
AB  - INTRODUCTION: As many as 20-30% of women report an inability to orgasm during
      sexual intercourse. Some female sexual problems have been reported to cluster
      with psychological and social problems. Underlying personality type may play a
      role in the development or maintenance of such problems. AIM: The aim of this
      study was to investigate whether certain domains of personality are associated
      with female coital orgasmic infrequency. To our knowledge this is the first such
      study in a large unselected population. METHODS: A total of 2632 women (mean age
      51) from the TwinsUK registry completed questionnaires relating to personality
      and sexual behavior. Personality domains were assessed using the validated Ten
      Item Personality Index (TIPI). Coital orgasmic frequency was measured using a
      seven-point Likert scale. MAIN OUTCOME MEASURES: Using logistic regression, we
      investigated whether variations in five domains of personality are associated
      with female coital orgasmic infrequency. Discordant twin analysis was used to
      verify findings. RESULTS: Introversion (odds ratio [OR] 2.5, 95% confidence
      interval [CI] 1.7-3.7), emotional instability (OR 2.0, 95% CI 1.3-3.1), and not
      being open to new experience (OR 2.4, 95% CI 1.6-3.6) were significantly
      associated with orgasmic infrequency, whereas indices of agreeableness and
      conscientiousness were not significantly associated with orgasm frequency.
      CONCLUSION: Specific personality subtypes appear to be significant risk factors
      for orgasmic infrequency. Consideration of these behavioral risk factors may need
      to be incorporated into research into female orgasmic disorder, and possible
      approaches to its treatment.

PMID- 18331254
TI  - Transsexualism in Serbia: a twenty-year follow-up study.
AB  - INTRODUCTION: Gender dysphoria occurs in all societies and cultures. The
      prevailing social context has a strong impact on its manifestations as well as on
      applications by individuals with the condition for sex reassignment treatment.
      AIM: To describe a transsexual population seeking sex reassignment treatment in
      Serbia, part of former Yugoslavia. METHODS: Data, collated over a period of 20
      years, from subjects applying for sex reassignment to the only center in Serbia,
      were analyzed retrospectively. MAIN OUTCOME MEASURES: Age at the time of
      application, demographic data, family background, sex ratio, the prevalence of
      polycystic ovarian syndrome (PCOS) among female-to-male (FTM) transsexuals, and
      readiness to undergo surgical sex reassignment were tabulated. RESULTS:
      Applicants for sex reassignment in Serbia are relatively young. The sex ratio is
      close to 1:1. They often come from single-child families. More than 10% do not
      wish to undergo surgical sex reassignment. The prevalence of PCOS among FTM
      transsexuals was higher than in the general population but considerably lower
      than that reported in the literature from other populations. Of those who had
      undergone sex reassignment, none expressed regret for their decision.
      CONCLUSIONS: Although transsexualism is a universal phenomenon, the relatively
      young age of those applying for sex reassignment and the sex ratio of 1:1
      distinguish the population in Serbia from others reported in the literature.

PMID- 18331255
TI  - Canadian and American sex therapists' perceptions of normal and abnormal
      ejaculatory latencies: how long should intercourse last?
AB  - INTRODUCTION: Lay public perceptions about how long intercourse should last are
      discrepant from objective data on ejaculatory latencies. This may be problematic
      as the subjective interpretation of latency is a factor related to perceived
      distress with length of intercourse. AIM: Quantify the opinion of expert sex
      therapists as to what are "adequate,""desirable,""too short," and "too long"
      intravaginal ejaculatory latencies. Method. A random sample of members of the
      Society for Sex Therapy and Research in the United States and Canada was
      surveyed. MAIN OUTCOME MEASURE: Intravaginal ejaculatory latency, in minutes, for
      four different conditions: coitus that lasts an amount of time that is
      "adequate,""desirable,""too short," and "too long." Results. The interquartile
      range for the sex therapists' opinions regarding an "adequate" length for
      ejaculatory latency was from 3 to 7 minutes; "desirable" from 7 to 13 minutes;
      "too short" from 1 to 2 minutes; "too long" from 10 to 30 minutes. CONCLUSIONS:
      Therapists' beliefs about ejaculatory latencies were consistent with objective
      data on ejaculatory latency and were not affected by therapist demographic
      characteristics such as sex or experience. These results suggest that the average
      sex therapist believes that intercourse that lasts 3 to 13 minutes is normative
      and not prima facie worthy of clinical concern. Dissemination to the public of
      these results may change lay expectations for intravaginal ejaculatory latency
      and prevent distress. These results may also be beneficial to couples in
      treatment for sexual problems by normalizing expectations.

PMID- 18331256
TI  - Clinical implications of a close vicinity of nervus dorsalis penis/clitoridis and
      os pubis.
AB  - INTRODUCTION: Close relation of nervus dorsalis penis/clitoris and os pubis has a
      major impact in surgical disciplines. AIM: To summarize a current knowledge about
      this region, represented by the course of sulcus nervi dorsalis penis/clitoridis.
      METHODS: Literature search of years 1970-2007. MAIN OUTCOME MEASURES: In male, it
      accommodates nervus dorsalis penis whereas in female nervus et arteria dorsalis
      clitoridis. Lateral border of sulcus nervi dorsalis penis corresponds to vertical
      ridge and lateral border of sulcus nervi dorsalis clitoridis to ventral arc-two
      parameters, which are parts of the Phenice's method for sexing of isolated os
      pubis. RESULTS: Exact preparation of nervus dorsalis penis is crucial in correct
      performance of conversion of genitalia in patients with transsexualism, in
      reconstruction of posterior urethra, in hypospadia, during performance of penile
      blockade during circumcision and in revascularization surgery of erectile
      dysfunction. Possible role of the sulcus nervi dorsalis penis in the Alcock's
      syndrome is discussed. Similarly, it is advisable to take care of nervus dorsalis
      clitoridis during reduction clitoridoplasty in patients with adrenogenital
      syndrome and during the insertion of transobturator vaginal tape. Injury of
      nervus dorsalis penis/clitoridis leads to hypesthesia or anesthesia of glans
      penis/clitoridis. The injury to arteria dorsalis clitoridis leads to bleeding
      and/or hematoma. CONCLUSIONS: Clinical anatomy of sulci is important in several
      situations in urologic surgery. It is possible to use sulcus nervi dorsalis
      penis/clitoridis for sexing of isolated pubis for anthropological or forensic
      purposes.

PMID- 18331257
TI  - Demographic and psychosocial features of participants in bondage and discipline,
      "sadomasochism" or dominance and submission (BDSM): data from a national survey.
AB  - INTRODUCTION: People with sexual interests in bondage and discipline,
      "sadomasochism" or dominance and submission (BDSM) have been seen by many
      professionals as damaged or dangerous. AIM: To examine sexual behavior correlates
      of involvement in BDSM and test the hypothesis that BDSM is practiced by people
      with a history of sexual coercion, sexual difficulties, and/or psychological
      problems. METHODS: In Australia in 2001-2002, a representative sample of 19,307
      respondents aged 16-59 years was interviewed by telephone. Weighted data analysis
      used univariate logistic regression. MAIN OUTCOME MEASURES: Self-reported
      demographic and psychosocial factors; sexual behavior and identity; sexual
      difficulties. RESULTS: In total, 1.8% of sexually active people (2.2% of men,
      1.3% of women) said they had been involved in BDSM in the previous year. This was
      more common among gay/lesbian and bisexual people. People who had engaged in BDSM
      were more likely to have experienced oral sex and/or anal sex, to have had more
      than one partner in the past year, to have had sex with someone other than their
      regular partner, and to have: taken part in phone sex, visited an Internet sex
      site, viewed an X-rated (pornographic) film or video, used a sex toy, had group
      sex, or taken part in manual stimulation of the anus, fisting or rimming.
      However, they were no more likely to have been coerced into sexual activity, and
      were not significantly more likely to be unhappy or anxious-indeed, men who had
      engaged in BDSM scored significantly lower on a scale of psychological distress
      than other men. Engagement in BDSM was not significantly related to any sexual
      difficulties. CONCLUSION: Our findings support the idea that BDSM is simply a
      sexual interest or subculture attractive to a minority, and for most participants
      not a pathological symptom of past abuse or difficulty with "normal" sex.

PMID- 18331258
TI  - Recreational use of PDE5 inhibitors by young healthy men: recognizing this issue
      among medical students.
AB  - INTRODUCTION: In recent years, recreational use of phosphodiesterase type 5
      (PDE5) inhibitors has become popular as a sexual enhancement aid among some men
      without erectile dysfunction (ED) and even among women. AIM: The aim of the
      present study, therefore, was to investigate the recreational use of PDE5 among
      young and healthy men. MAIN OUTCOME MEASURES: We evaluated the use of PDE5
      inhibitors among young and healthy men, their main reasons for using these drugs,
      and their expectations regarding its effects. METHODS: A survey was carried out
      among 167 male medical students (21.2 +/- 2.3 years, range 17-31). The surveys
      were divided into domains, assessing epidemiological data, use of PDE5 inhibitor,
      and the simplified International Index of Erectile Function (IIEF-5). RESULTS:
      All men considered themselves with perfect erectile function. However, 9%
      reported previous use of PDE5 inhibitors. Of these, 46.7% had used PDE5
      inhibitors more than three times, and 71.4% had mixed them with alcohol. Among
      this group of men, 13.3% had ED according to the IIEF-5. ED occurring with condom
      use, however, was twice more common, and 71.4% of the men who had taken PDE5
      inhibitors thought that the drug had potential to facilitate condom use.
      CONCLUSION: In conclusion, the use of PDE5 inhibitors by young men is more
      frequent than previously reported. Condom-related ED seems to be an
      underestimated problem, frequently solved with PDE5 inhibitors. However,
      potential deleterious effects might exist. Because PDE5 inhibitors are being used
      as non-prescribed drugs by as much as 9% of young men, further studies must
      evaluate the effects of these drugs in young and healthy men.

PMID- 18331260
TI  - The use of old and recent DSM definitions of premature ejaculation in
      observational studies: a contribution to the present debate for a new
      classification of PE in the DSM-V.
AB  - INTRODUCTION: The DSM-III definition of premature ejaculation (PE) contains the
      criterion "control" but not that of "ejaculation time." In contrast, the
      Diagnostic and Statistical Manual of Mental Disorders (4th edition, Text
      Revision) (DSM-IV-TR) contains the criterion "short ejaculation time," while it
      lacks "control." AIM: To review the adequacy and consequent use of all criteria
      of the DSM-IV-TR definition in previously published PE Internet surveys. METHODS:
      Reviewing all published cohort studies on PE from 2004 to 2007. MEDLINE and
      EMBASE computer bibliographies were used. MAIN OUTCOME MEASURE: Definitions of
      DSM-III, DSM-IV-TR, and International Classification of Diseases. RESULTS: Five
      papers, of which three are original studies, reported inclusion of men with PE
      according to DSM-IV-TR definition but omitted to apply the required "short
      ejaculation time" criterion. These studies, which have defined PE according to
      subjective criteria such as control, actually referred to the DSM-III definition.
      Using DSM-III-like definitions in three different studies revealed a highly
      variable prevalence of PE (32.5%, 27.6%, and 13.0%). In contrast, based on
      studies using a 1-minute cutoff point, being the time that is required to call
      ejaculation time "short" or using the criterion "persistent occurrence," PE
      revealed to be far less prevalent (5-6%). CONCLUSIONS: Unacceptable discrepancies
      of PE definitions according to DSM-III (abandoned but still used) and DSM-IV-TR
      argue strongly in favor of a multidimensional new classification of PE for the
      DSM-V.

PMID- 18331261
TI  - Sexual function and psychological status among males and females with ischemic
      heart disease.
AB  - INTRODUCTION: Patients with coronary artery disease (CAD) may also suffer from
      mental and sexual problems, and we should consider the mutual influence such
      conditions have on each other. However, the interrelation between sexual and
      mental problems in the context of CAD has not been fully investigated, especially
      when it comes to gender. AIM: Our aim was to evaluate sexuality and psychiatric
      symptoms among patients with CAD and the relation between them in each gender.
      METHODS: In this cross-sectional study, 550 (397 men and 153 women) patients with
      documented CAD were surveyed for anxiety and depression using the hospital
      anxiety and depression scale (HADS) self-administered questionnaire as well as
      the relation and sexuality scale (RSS). Three subscores were calculated for
      sexual function, frequency, and fear, with higher scores indicative of a poorer
      condition. MAIN OUTCOME MEASURES: The HADS and the RSS. RESULTS: Depressive
      symptoms and anxiety were more severe among our female subjects than they were
      among the male ones. In addition, the scores for sexual frequency, sexual
      function, and the total RSS were significantly higher in women, while men had a
      significantly higher score for sexual fear. The total RSS score correlated with
      depressive symptoms in women (r = 0.19, P = 0.03), but not in the male subjects.
      Considering the subscores, a higher score for sexual frequency correlated with
      depressive symptoms in both genders; however, being afraid of sexual relation
      correlated with depressive symptoms only in men with CAD and their spouses (r =
      0.18, P = 0.001). CONCLUSION: We found that women with CAD have poorer sexual
      relation and more severe depressive symptoms than men do. Among men with CAD and
      their wives, fear of sexual relationship is a more serious problem. Such gender
      specific characteristics and their interrelations ought to receive due
      consideration in the management of CAD.

PMID- 18331262
TI  - Strain differences in susceptibility to in vivo erectile dysfunction following 6
      weeks of induced hyperglycemia in the mouse.
AB  - INTRODUCTION: With the large-scale availability of transgenic and knockout mouse
      models, the use of mice may greatly facilitate the examination of the mechanisms
      underlying diabetic erectile dysfunction (ED). Although in vitro studies of the
      mouse cavernosum show impairment of vasoreactivity, to date, no studies have
      demonstrated the in vivo impairment of erectile function in diabetic mice. AIM:
      To establish whether mouse models of type I diabetes exhibit in vivo ED. METHODS:
      Hyperglycemia was induced by injection with streptozotocin (STZ, 125 mg/kg x 2
      days) in two mouse strains, C57BLKS (BKS) and BALB/c. Six weeks after injection,
      the cavernosum was removed from some mice for the in vitro assessment of the
      endothelium and nerve-mediated dilatory responses of the cavernosal strips. The
      in vivo assessment of intracorporal pressure normalized to mean arterial
      pressure, in response to the electrical stimulation of the cavernosal nerve, was
      performed in the remaining mice. MAIN OUTCOME MEASURES: The main outcome measure
      of this study was the in vivo assessment of erectile function following diabetic
      induction in mice. RESULTS: Despite similar levels of sustained hyperglycemia
      following STZ injection, the phenotype of diabetic ED was observed only in BKS
      and not BALB/c mice. The cavernosum from diabetic BKS mice showed decreased
      endothelium-dependent dilation in response to acetylcholine (ACh), as well as
      impaired parasympathetic nerve-mediated relaxation. There was no change in ACh or
      nerve-mediated relaxation in the cavernousum from diabetic vs. control BALB/c
      mice. Further, in vivo physiologic assessment of erectile activity revealed a
      significant decrease in erectile function in diabetic BKS but not in BALB/c mice.
      CONCLUSION: Together these data first established in vivo ED in a mouse model of
      type I diabetes (BKS mouse) and importantly demonstrated that certain inbred
      strains may be protected from hyperglycemia-induced erectile impairment. Further
      study of the strain-dependent effects may offer important clues into the
      mechanisms of ED as it relates to type I diabetes.

PMID- 18331259
TI  - Therapeutic response after first month of tadalafil treatment predicts 12 months
      treatment continuation in patients with erectile dysfunction: results from the
      DETECT study.
AB  - INTRODUCTION: The DETECT study is a prospective, 12-month, European, multicenter,
      observational study of patients with erectile dysfunction (ED) initiating or
      changing treatment to tadalafil in routine clinical practice. AIM: To determine
      the effectiveness of tadalafil and the factors associated with the continuation
      of treatment for ED at 12 months. METHODS: The DETECT study included 1,900 men
      aged 18 years and older with a history of ED and who were initiating or changing
      treatment to tadalafil. MAIN OUTCOME MEASURES: Sexual function at baseline, 1, 6,
      and 12 months was assessed using the International Index of Erectile Function
      erectile function (IIEF-EF) domain. Factors associated with treatment
      continuation at 12 months were evaluated using multivariate regression analysis.
      RESULTS: At 12 months, 1,319 (84%) of 1,567 patients who completed the
      questionnaire reported continued use of tadalafil. Among these patients,
      tadalafil was highly effective: 94%, 95%, and 71% with severe, moderate, and mild
      ED at baseline, respectively, improved by at least one IIEF-EF category and 65%
      had normal EF. Five factors were associated with tadalafil continuation at 12
      months: (i) ED severity at 1 month (based on IIEF-EF domain score); (ii)
      tolerance to treatment at 1 month; (iii) age younger than 60 years; (iv) number
      of sexual attempts in the first month; and (v) no history of pelvic surgery.
      Patient and partner factors at baseline were not significantly associated with
      continued tadalafil use. CONCLUSIONS: Tadalafil is an effective treatment for ED
      in routine clinical practice. The therapeutic response and treatment tolerance
      after 1-month treatment are the most important factors influencing tadalafil
      continuation.

PMID- 18331263
TI  - Vaginal orgasm is associated with less use of immature psychological defense
      mechanisms.
AB  - INTRODUCTION: Freud implied a link between inability to have a vaginal orgasm and
      psychosexual immaturity. Since Kinsey, many sexologists have asserted that no
      such link exists. However, empirical testing of the issue has been lacking. AIM:
      The objective was to determine the relationship between different sexual behavior
      triggers of female orgasm and use of immature psychological defense mechanisms.
      METHODS: Women reported their past month frequency of different sexual behaviors
      and corresponding orgasm rates and completed the Defense Style Questionnaire (DSQ
      40). MAIN OUTCOME MEASURE: The association between ability to have vaginal
      intercourse orgasm (versus clitoral orgasm) and the use of DSQ-40 immature
      psychological defense mechanisms (associated with various psychopathologies) was
      examined. RESULTS: In a sample of 94 healthy Portuguese women, vaginal orgasm
      (triggered solely by penile-vaginal intercourse) was associated with less use of
      DSQ-40 immature defenses. Vaginal orgasm was associated with less somatization,
      dissociation, displacement, autistic fantasy, devaluation, and isolation of
      affect. Orgasm from clitoral stimulation or combined clitoral-intercourse
      stimulation was not associated with less use of immature defenses, and was
      associated with more use of some immature defenses. In one regression analysis,
      more masturbation and less vaginal orgasm consistency made independent
      contributions to the statistical prediction of immature defenses. In another
      regression analysis, any use of extrinsic clitoral stimulation for intercourse
      orgasm, and lack of any vaginal orgasm, made independent contributions to the
      statistical prediction of immature defenses. Vaginally anorgasmic women had
      immature defenses scores comparable to those of established (depression, social
      anxiety disorder, panic disorder, and obsessive-compulsive disorder) outpatient
      psychiatric groups. Results were not confounded by social desirability responding
      or relationship quality. CONCLUSIONS: The results linking penile-vaginal orgasm
      with less use of immature psychological defense mechanisms are consistent with
      both early psychoanalytic personality theory and recent advances in sexual
      physiology. Implications for diagnosis and sex therapy are noted.

PMID- 18331264
TI  - Management of distal extrusion of penile prosthesis: partial disassembly and tip
      reinforcement by double breasting or grafting.
AB  - INTRODUCTION: Distal erosion and perforation of penile prosthesis have been
      reported in association with neurologic impairment, diabetes mellitus, and
      following irradiation for prostatic cancer. Once perforation occurs,
      reimplantation carries a higher risk of reperforation unless adequate preventive
      measures are taken. Aim. This is a description of a procedure whereby the point
      of perforation was exposed and repaired to restore distal support. METHODS: In
      three patients with distal extrusion of penile prosthesis through the urethra,
      the glans was mobilized off the tip of the corpus cavernosum and the caverno
      urethral fistula was disconnected from the corpus cavernosum. The fistula was
      sealed by primary sutures. The perforation on the corpus cavernosum side was
      sealed by double breasting in two cases and by grafting in one case. Prosthesis
      was reimplanted. MAIN OUTCOME MEASURES: Complications, recurrence of erosion, and
      postoperative coital pain. RESULTS: No complications, recurrence, or persistent
      pain occurred in any of the three cases. CONCLUSION: The management of the distal
      extrusion of penile prosthesis by partial disassembly, double breasting, or
      grafting may provide reliable distal support and thereby avoid reperforation and
      repeated extrusion.

PMID- 18331265
TI  - Prevalence and correlates of three types of pelvic pain in a nationally
      representative sample of Australian men.
AB  - INTRODUCTION: Recent international prevalence studies of pelvic pain in men have
      estimates ranging between 2% and 10%. These studies conclude that it is an
      important international health problem. AIMS: The aims of this study were to
      establish the first population-based study of pelvic pain in Australian men, and
      identify correlates with men's sexual and reproductive histories and other health
      conditions. METHODS: A representative household sample of 4,290 Australian men
      aged 16-64 years completed a computer-assisted telephone interview. They were
      asked about their experiences of pain in the pelvic region during the past 12
      months. MAIN OUTCOME MEASURES: Prevalence of correlates of pain associated with
      sexual intercourse, pain associated with urination, and pelvic pain not
      associated with intercourse or urination. RESULTS: Five percent of men reported
      pain during urination, 5% reported pain related to sexual intercourse, and 12% of
      men reported other chronic pelvic pain. There was little overlap in reporting any
      of the three types of pelvic pain, with 18% of men reporting some form of pelvic
      pain. Men reporting any of the pain conditions were significantly more likely
      than other men to report a sexual experience when they had felt forced or
      frightened. Men reporting pain during intercourse and/or chronic pelvic pain were
      significantly more likely than other men to report same sex experience. All three
      groups of men with pelvic pain were more likely than other men to report some
      form of sexual difficulties. A report of ever receiving a diagnosis of depression
      or a report of anxiety was significantly associated with all forms of pelvic
      pain. CONCLUSIONS: More than one man in six report having some form of pelvic
      pain in the past 12 months. It is likely that men would benefit from a discussion
      about possible symptoms during consultations with their physicians.

PMID- 18331266
TI  - Sex steroids and leptin regulate the "first Kiss" (KiSS 1/G-protein-coupled
      receptor 54 system) in human gonadotropin-releasing-hormone-secreting
      neuroblasts.
AB  - INTRODUCTION: The G-protein-coupled receptor 54 (GPR54) and its ligand
      kisspeptin, encoded by the KiSS-1 gene, have been involved in the molecular
      mechanisms underlying the reawakening of gonadotropin-releasing hormone (GnRH)
      neurons at puberty. GPR54 mutations cause hypogonadotropic hypogonadism in human
      and mice. Aim. Our aim was to study regulation of the KiSS-1/GPR54 system using a
      previously characterized primary culture of human fetal GnRH-secreting
      neuroblasts, FNC-B4. METHODS: KiSS-1/GPR54 gene and protein expressions in FNC-B4
      were evaluated by quantitative reverse transcription-polymerase chain reaction
      (qRT-PCR), immunocytochemistry, and Western blot. Expression of kisspeptin and
      GPR54 in fetal olfactory mucosa (OM), from which FNC-B4 cells were derived, was
      analyzed with confocal microscopy. MAIN OUTCOME MEASURES: Regulation of KiSS
      1/GPR54 expression in FNC-B4 was evaluated in response to sexual steroids and
      leptin. Effect of kisspeptin on GnRH secretion and migration in FNC-B4 was also
      investigated. RESULTS: Kisspeptin and GPR54 were immunolocalized and co-expressed
      with GnRH in OM and FNC-B4 cells. Kisspeptin (1 microM, 24 hours) induced GnRH
      secretion, but not gene expression, and inhibited migration (IC(50) = 6.28 +/-
      3.71 nM) in FNC-B4. The 24-hour exposure to increasing concentrations of 17-beta
      estradiol (0.01-1 nM) significantly and dose-dependently decreased, whereas
      androgens (dihydrotestosterone [DHT], 0.01-1 nM) significantly stimulated KiSS
      1/GPR54 mRNA. Testosterone (1 nM) showed a stimulatory effect only after blocking
      its aromatization with letrozole. In addition, leptin (1 nM, 24 hours), an
      adipocyte-derived hormone acting on the reproductive axis, significantly
      increased KiSS-1/GPR54 expression in FNC-B4. Immunocytochemistry and Western blot
      analysis confirmed the regulatory effects found with qRT-PCR. Interestingly,
      leptin (1 nM, 24 hours) also significantly increased both leptin receptor (LEPR)
      and androgen receptor (AR) mRNA. DHT (0.01-1 nM) also up-regulated LEPR and AR
      genes, suggesting a synergistic action between leptin and androgens aimed to up
      regulate the KiSS-1/GPR54 system, which, in contrast, was inhibited by estrogens.
      CONCLUSION: Our results indicate that an interplay between metabolic and sexual
      hormones may trigger the KiSS-1/GPR54 signaling to GnRH neurons suggesting new
      mechanisms which regulate puberty onset.

PMID- 18331267
TI  - Assessment of sexual health in aging men in Europe: development and validation of
      the European Male Ageing Study sexual function questionnaire.
AB  - INTRODUCTION: Assessment of male sexual dysfunction has been the focus of
      substantial scientific effort. Less research has focused on the development of
      instruments for the measurement of sexual functioning in aging men. AIMS: The
      aims of this study were: (i) to characterize the psychometric properties of a new
      brief, reliable, and valid measure of male sexual functioning for use in a large
      population survey of middle-aged and elderly European men; and (ii) specifically,
      to determine whether the new instrument, the European Male Ageing Study-sexual
      function questionnaire (EMAS-SFQ), discriminates between men with high and low
      levels of circulating testosterone (T) (total T, free T, and bioavailable T).
      METHOD: One thousand six hundred men aged 40-79 years completed the self
      administered EMAS-SFQ, the Beck depression inventory, and provided a blood sample
      for assessment of sex hormones. Eighty-five men aged 35-74 years completed the
      EMAS-SFQ twice, 2 weeks apart to examine the test-retest reliability of the
      instrument. MAIN OUTCOME MEASURES: Scores on the EMAS-SFQ in relation to age and
      T levels. RESULTS: Principal component analysis showed that the EMAS-SFQ had four
      distinct domains (overall sexual functioning [OSF], masturbation, sexual
      functioning-related distress, and change in sexual functioning). The instrument
      demonstrated excellent internal and test-retest reliability, as well as
      convergent, divergent, and discriminant validity. Men with the lowest levels of
      total, free, and bioavailable T reported lower OSF scores compared to men with
      the highest T levels. CONCLUSIONS: The EMAS-SFQ is a valid and reproducible
      instrument, sensitive to age and T levels. It should be suitable for the
      assessment of sexual health in population samples of men in epidemiological
      studies of aging.

PMID- 18331268
TI  - Sexual function in well women: stratification by sexual satisfaction, hormone
      use, and menopause status.
AB  - INTRODUCTION: Satisfaction with sexual function in community-based women has not
      been well-described, and little is known of differences in sexual function
      between pre-(PreM) and postmenopausal (PM) women. AIM: The aim of this article
      was to describe sexual function in PreM and PM women who self-identify as being
      satisfied or dissatisfied with their sexual life. METHODS: A cross-sectional
      questionnaire study was conducted among 349 sexually active community-based
      women, aged 20-65 years, who self-identified as being either satisfied or
      dissatisfied with their sexual life. MAIN OUTCOME MEASURES: Scores from a daily
      diary of sexual function for 4 weeks, examining the frequency of sexual thoughts,
      interest, and activity. RESULTS: One hundred and eighty-four women (53%) were
      PreM, and 165 (47%) were dissatisfied with their sexual life. The median number
      of days with sexual activity or events per month for all women was 8 (ranges 2-28
      days; 2-57 events). Ninety-two percent of reported events involved a partner, 86%
      involved intercourse, and in 40% the woman initiated the activity. Women
      satisfied with their sexual life had higher frequencies of sexual thoughts,
      interest, events, and initiation of activity than dissatisfied women (P <
      0.0001). PreM satisfied women had higher frequencies of sexual thoughts, numbers
      of days with sexual activity, and events per month than PM satisfied women (P <
      0.05). PreM oral contraceptive pill (OCP) users had significantly lower average
      frequencies of sexual thoughts, interest, and days of sexual activity per month
      (P < 0.05), whereas PM women hormone therapy (HT) users had higher frequencies of
      sexual thoughts and sexual interest (P = 0.04 and P = 0.05, respectively)
      compared to nonusers. There were no differences in sexual function between PreM
      and PM women who were sexually dissatisfied. CONCLUSIONS: Sexual activity mostly
      involved a partner, partner initiation, and intercourse. Sexually satisfied women
      reported more sexual thoughts, interest, events, and initiation of sexual
      activity than dissatisfied women. PreM sexually satisfied women reported more
      sexual thoughts, days with sexual activity, and sexual events per month compared
      to PM satisfied women. OCP and HT use appeared to have contrasting effects on
      sexual function.

PMID- 18331269
TI  - The inhibitory effects of nicotine on physiological sexual arousal in nonsmoking
      women: results from a randomized, double-blind, placebo-controlled, cross-over
      trial.
AB  - INTRODUCTION: Extensive research suggests that long-term cigarette smoking is an
      independent risk factor for the introduction of sexual dysfunction in men.
      However, results of limited data investigating this relationship in women are
      mixed. No studies have examined the acute effects of tobacco or nicotine on
      physiological sexual response in women. Controlled experimental studies examining
      acute effects of isolated nicotine intake on female physiological sexual
      responses are necessary in order to help elucidate tobacco's potential role in
      the development and/or maintenance of sexual impairment in women. AIM: To examine
      whether isolated nicotine intake acutely affects sexual arousal responses in
      nonsmoking women. METHODS: Twenty-five sexually functional women (mean age = 20
      years) each with less than 100 direct exposures to nicotine completed two
      counterbalanced conditions in which they were randomized to received either
      nicotine gum (6 mg) or placebo gum, both administered double-blind and matched
      for appearance, taste, and consistency, approximately 40 minutes prior to viewing
      an erotic film. MAIN OUTCOME MEASURES: Physiological (changes in vaginal pulse
      amplitude via vaginal photoplethysmography) and subjective (continuous self
      report) sexual responses to erotic stimuli were examined, as well as changes in
      mood. RESULTS: Nicotine significantly reduced genital responses to the erotic
      films (P = 0.05), corresponding to a 30% attenuation in physiological sexual
      arousal. This occurred in 11 of 18 women with valid physiological assessments.
      Nicotine had no significant effect on continuous self-report ratings of sexual
      arousal (P = 0.45), or on mood (all Ps > 0.05). CONCLUSIONS: Acute nicotine
      intake significantly attenuates physiological sexual arousal in healthy
      nonsmoking women. Our findings provide support to the hypothesis that nicotine
      may be the primary pharmacological agent responsible for genital hemodynamic
      disruption, thereby facilitating a cascade of biochemical and vascular events
      which may impair normal sexual arousal responses.

PMID- 18331270
TI  - Nitric oxide synthesis leads to vascular endothelial growth factor synthesis via
      the NO/cyclic guanosine 3',5'-monophosphate (cGMP) pathway in human corpus
      cavernosal smooth muscle cells.
AB  - INTRODUCTION: Vascular smooth muscle cells express endothelial nitric oxide
      synthase (eNOS) and produce nitric oxide (NO). Recently, increased NO production
      has been reported to induce the synthesis and secretion of vascular endothelial
      growth factor (VEGF) via the NO/cyclic guanosine 3',5'-monophosphate (cGMP)
      pathway. L-arginine (L-arg), the precursor of NO, and selective phosphodiesterase
      type 5 (PDE-5) inhibitors that increase levels of intracellular cGMP may
      complementarily enhance VEGF synthesis in corpus cavernosal smooth muscle cells
      (CCSMCs), and may consequently restore impaired endothelial function. Expression
      of eNOS in corpus cavernosal smooth muscle has also been reported. However, it is
      unclear whether CCSMCs can generate NO. AIM: To elucidate whether CCSMCs can
      synthesize NO and whether NO synthesis enhances VEGF synthesis via the NO/cGMP
      pathway. METHODS: Corpus cavernosal cells were cultured and characterized by
      immunocytochemistry and immunoblotting. CCSMCs were treated with L-arg. CCSMCs
      were also incubated with L-arg and with vardenafil, an inhibitor of PDE-5. MAIN
      OUTCOME MEASURES: Release of NO from cells was confirmed by assay of NO
      metabolites (NOx). Intracellular cGMP concentration and VEGF concentration in the
      medium were measured. RESULTS: Isolated cells were determined to be CCSMCs. The
      expression of eNOS by CCSMCs was also identified. NOx and cGMP levels in the L
      arg-treated group were significantly greater than those in the control group.
      VEGF and cGMP levels in the L-arg-treated group were also significantly greater
      than those in the control group. VEGF and cGMP levels in the L-arg + vardenafil
      treated group were significantly greater than those in the L-arg-treated group
      and the control group. CONCLUSIONS: CCSMCs express eNOS and synthesize NO. NO
      synthesis leads to enhancement of VEGF synthesis via the NO/cGMP pathway.
      Combined L-arg and vardenafil treatment, which can enhance VEGF production, may
      provide a novel therapeutic strategy for the treatment of erectile dysfunction as
      well as endothelial dysfunction in general.

PMID- 18331271
TI  - Erectile dysfunction and dyslipidemia: relevance and role of phosphodiesterase
      type-5 inhibitors and statins.
AB  - INTRODUCTION: There is a close link between hyperlipidemia/dyslipidemia and
      erectile dysfunction (ED), with endothelial dysfunction as a common mechanism.
      Both ED and hyperlipidemia/dyslipidemia are rising in prevalence with mounting
      evidence that these conditions are harbingers of cardiovascular disease. AIM:
      This review was conducted to provide an update on the epidemiology and oral
      therapy of both dyslipidemia and ED, the connection between these two conditions,
      and clinical outcomes relating to the use of statins and phosphodiesterase type-5
      (PDE5) inhibitors in men with ED who have associated dyslipidemia. METHODS: A
      systematic search was performed of MEDLINE and EMBASE research databases to
      obtain articles pertaining to the epidemiology, mechanism, and clinical outcomes
      of statins and PDE5 inhibitors in men with ED and associated dyslipidemia. MAIN
      OUTCOME MEASURES: The clinical and preclinical studies related to ED and
      dyslipidemia are analyzed and their findings are assessed and summarized.
      Results. Hyperlipidemia/Dyslipidemia constitute a vascular risk factor having a
      considerable impact on erectile function. Furthermore, the role of endothelial
      dysfunction in the pathophysiology of both ED and dyslipidemia is paramount
      suggesting the importance of comanaging these conditions. Therefore,
      hyperlipidemia/dyslipidemia when present in patients with ED should prompt
      management with diet/exercise as well as appropriate pharmacotherapy. With ED
      being often associated with comorbidities, the use of concomitant
      pharmacotherapies enhances opportunities for managing the overall global
      cardiometabolic risk. Newer studies assessing the effect of PDE5 inhibitors in
      men with dyslipidemia will shed more light on the clinical profile of these
      agents when used in this patient population. CONCLUSIONS: While dyslipidemia and
      ED are important concerns for clinicians, there exists a gap that needs to be
      closed between the number of individuals who have either or both conditions and
      those who are receiving appropriate therapy based on evidence and patient-driven
      goals regarding clinical outcomes.

PMID- 18331272
TI  - FK506 and erectile function preservation in the cavernous nerve injury model:
      optimal dosing and timing.
AB  - INTRODUCTION: The immunophilin-ligand FK506 has been shown to ameliorate erectile
      function and preserve cavernous nerve (CN) architecture in short-term-studies
      using rat models of CN injury. AIM: The aim of this series was to ascertain the
      optimal dose and timing of FK506 administration in this animal model. METHODS:
      Rats underwent bilateral CN crush and were treated with FK506 at different time
      points. There were control (C) and sham groups for each time point. Based on
      preliminary experiments, the CN-crush rats had no treatment (C) or either FK506 1
      mg/kg (BL) or 3.2 mg/kg (BH) for 3 days prior to and the day of CN crush (PRE),
      on the day of and for 3 days following CN crush (POST) and for 3 days pre-, on
      the day of, and 3 days post-CN crush (PP). MAIN OUTCOME MEASUREMENTS: All animals
      had measurement of intracavernosal pressure/mean arterial blood pressure
      (ICP/MAP) ratios at 28 days post-CN crush. Structural analysis was conducted in
      the POST groups. Penile tissue was assessed for apoptosis with terminal
      deoxynucleotidyl transferase biotin-dUTP nick end labeling assay and
      immunohistochemically for neural factors (growth associated protein 43 [GAP43],
      nerve growth factor [NGF], and neural nitric oxide synthase [nNOS]). The CN
      architecture was examined by transmission electron microscopy (TEM). RESULTS:
      Sham animals had an ICP/MAP ratio of 70%. Only the BH-POST group revealed an
      improved ICP/MAP ratio compared with C (50 +/- 9% vs. 32 +/- 8%, P < 0.01). nNOS
      staining was significantly restored reaching sham levels in BL-POST and BH-POST
      groups vs. C (P < 0.05). NGF and GAP43 staining displayed no significant
      differences between C and treatment groups (P < 0.05). Apoptosis was
      significantly reduced in BL-POST and BH-POST groups compared with C (16 +/- 4%,
      21 +/- 9%, and 63 +/- 7%, P < 0.001). TEM exhibited preservation of CN
      architecture for BH-POST compared with C. CONCLUSION: These results suggest that
      short-term treatment with doses of FK506 higher than previously utilized
      preserves erectile function in the rat CN-injury model. Pretreatment appears to
      offer no advantage. However, FK506 administration just prior to CN injury and for
      a short-time post-injury achieves the best functional and structural preservation
      outcomes.

PMID- 18331273
TI  - Cigarette smoking and erectile dysfunction: focus on NO bioavailability and ROS
      generation.
AB  - INTRODUCTION: Thirty million men in the United States suffer from erectile
      dysfunction (ED) and this number is expected to double by 2025. Considered a
      major public health problem, which seriously affects the quality of life of
      patients and their partners, ED becomes increasingly prevalent with age and
      chronic smoking is a major risk factor in the development of ED. AIM: To review
      available evidence concerning the effects of cigarette smoking on vascular
      changes associated with decreased nitric oxide (NO) bioavailability and increased
      reactive oxygen species (ROS) generation. METHODS: We examined epidemiological
      and clinical data linking cigarette smoking and ED, and the effects of smoking on
      vascular NO bioavailability and ROS generation. MAIN OUTCOME MEASURES: There are
      strong parallels between smoking and ED and considerable evidence supporting the
      concept that smoking-related ED is associated with reduced bioavailability of NO
      because of increased ROS. RESULTS: Cigarette smoking-induced ED in human and
      animal models is associated with impaired arterial flow to the penis or acute
      vasospasm of the penile arteries. Long-term smoking produces detrimental effects
      on the vascular endothelium and peripheral nerves and also causes ultrastructural
      damage to the corporal tissue, all considered to play a role in chronic smoking
      induced ED. Clinical and basic science studies provide strong indirect evidence
      that smoking may affect penile erection by the impairment of endothelium
      dependent smooth muscle relaxation or more specifically by affecting NO
      production via increased ROS generation. Whether nicotine or other products of
      cigarette smoke mediate all effects related to vascular damage is still unknown.
      CONCLUSIONS: Smoking prevention represents an important approach for reducing the
      risk of ED. The characterization of the components of cigarette smoke leading to
      ED and the mechanisms by which these components alter signaling pathways
      activated in erectile responses are necessary for a complete comprehension of
      cigarette smoking-associated ED.

PMID- 18331274
TI  - The functional and structural consequences of cavernous nerve injury are
      ameliorated by sildenafil citrate.
AB  - INTRODUCTION: Radical prostatectomy (RP) is associated with erectile dysfunction
      (ED). A single, placebo-controlled, human study has assessed the effects of
      regular sildenafil use after RP and demonstrated an increased chance of
      preservation of preoperative erectile function. Aim. This study was undertaken to
      define the effects of such a regimen in an animal model. METHODS: Using the
      cavernous nerve (CN) crush injury model, animals were divided into a number of
      groups: no CN injury (sham), bilateral CN injury exposed to either no sildenafil
      (control) or sildenafil at two doses (10 and 20 mg/kg) subcutaneously daily for
      three different durations (3, 10, 28 days). MAIN OUTCOME MEASURES: At these time
      points, CN electrical stimulation was used to assess erectile function by mean
      intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio. For the
      structural analyses, whole rat penes were harvested. Staining for Masson's
      trichrome was utilized to calculate the smooth muscle-collagen ratio.
      Immunohistochemical antibody staining was performed for endothelial (CD31 and
      eNOS) and neural (GAP43, NGF, and nNOS) factors and immunoblotting was performed
      to analyze the AKT/eNOS pathway. Terminal deoxynucleotidyl transferase biotin
      dUTP nick end labeling (TUNEL) assay was used for the assessment of apoptotic
      indices and the CN architecture was evaluated by transmission electron microscopy
      (TEM). RESULTS: Erectile function was improved with sildenafil in a time- and
      dose-dependent fashion with maximization of erectile function recovery occurring
      with daily 20 mg/kg at the 28-day time point. Sildenafil use resulted in smooth
      muscle-collagen ratio protection and CD31 and eNOS expression preservation.
      Sildenafil reduced apoptotic indices significantly compared with control. Animals
      exposed to sildenafil had increased phosphorylation of akt and eNOS. Tem
      demonstrated distinct differences in architecture between control and sildenafil
      groups toward an increased amount of myelinized nerve fibers. CONCLUSIONS:
      Sildenafil use in the CN crush injury model preserves erectile function that
      appears to be mediated predominantly through preservation of smooth muscle
      content and endothelial function as well as through reduction in apoptosis.

PMID- 18331275
TI  - Contractile changes of the clitoral cavernous smooth muscle in female rabbits
      with experimentally induced overactive bladder.
AB  - INTRODUCTION: Recently, growing clinical evidence has suggested that sexual
      dysfunction is more prevalent in women with overactive bladder (OAB). Aims.
      However, there has been no basic research to clarify the relationship between OAB
      and female sexual dysfunction. Therefore, we investigated this issue using a
      rabbit model of OAB. METHODS: Twenty-seven New Zealand white female rabbits were
      randomly divided into the OAB and control groups. MAIN OUTCOME MEASURES: The
      contractile responses of clitoral cavernous strips to K(+), phenylephrine (PE),
      Bay K 8644, and endothelin (ET)-1, and the relaxation responses of acetylcholine
      (ACh), sodium nitroprusside (SNP), and Y-27632 to PE-induced contraction by
      measuring isometric tension. Results. The contractile responses to K(+), PE, Bay
      K 8644, and ET-1 were significantly more increased in the OAB group in a dose
      dependant manner than in the control group (P < 0.05), and the responses to ET-1
      were more prominent than those to the remaining substances (P < 0.01). The
      increased contractile responses to ET-1 were blocked by BQ123 (ET(A) receptor
      antagonist) but not by BQ788 (ET(B) receptor antagonist). Clitoral cavernosal
      strips from the OAB group were more difficult to relax than those from the
      control group in terms of ACh- and SNP-induced relaxation (P < 0.05). The Y-27632
      induced relaxant responses to PE- and ET-1-induced contraction were less
      prominent in the OAB group than in the control group. CONCLUSIONS; The results of
      this study provide evidence that female OAB may deteriorate clitoral engorgement,
      which is associated with a greater force generation by increased calcium
      sensitization and subsequently decreased of relaxation. The activation of ET and
      Rho-kinase system may be crucial to negatively effect the clitoral smooth muscle
      relaxation in experimentally induced OAB animal model. But whether these
      vasomotor effects are revived in human clitoris is still debatable.

PMID- 18331276
TI  - Maladaptive personality traits and psychopathology in childhood and adolescence:
      the moderating effect of parenting.
AB  - This study examines child and adolescent psychopathology from a maladaptive trait
      perspective, incorporating both parental and child ratings of parenting as a
      moderator of the personality-psychopathology association. Hierarchical moderated
      regression analyses were conducted on a combined sample of referred and
      nonreferred children and adolescents (N=862, parental ratings of parenting and
      N=396, child ratings of parenting). The results indicated positive main effects
      of maladaptive traits on externalizing and internalizing problems, and positive
      main effects of parental negative control on externalizing problems. Significant
      interactions were found for Disagreeableness and Emotional Instability with
      parental Negative Control and for Disagreeableness x Positive Parenting in
      explaining externalizing problems. The discussion focuses on the contribution of
      these findings to a better understanding of the trait-psychopathology
      relationship at young age.

PMID- 18331277
TI  - What makes a hero? The impact of integrity on admiration and interpersonal
      judgment.
AB  - Principled and expedient ideologies affect self-regulation and guide people along
      divergent ethical paths. A more principled ideology, indicative of higher claimed
      integrity, involves a greater personal commitment to ethical beliefs, standards,
      and self-schemas that facilitate positive social activities and help resist the
      temptation of illicit activities. Two studies showed that differences in reported
      integrity are related to people's preferences for and judgments of others. Those
      higher in integrity spontaneously described their heroes as more principled,
      honest, spiritual, and benevolently oriented toward others (Study 1). In
      addition, integrity was related to people's evaluations of characters who made
      ethical or unethical career decisions (Study 2). The judgments of those higher in
      integrity were greatly influenced by whether or not the decision was ethical but
      were largely unaffected by the consequences (career success or failure), whereas
      those lower in integrity were less influenced by whether the decision was ethical
      and more influenced by the career consequences.

PMID- 18331278
TI  - Self-esteem differences in the effects of hypocrisy induction on behavioral
      intentions in the health domain.
AB  - Two studies investigated whether individuals with varying levels of self-esteem
      respond differently in the hypocrisy paradigm. In the first study, all
      participants were regular smokers. Those in the hypocrisy condition delivered a
      speech in front of a camera on the dangers of smoking. The principal dependent
      measure was the intention to stop smoking. In the second study, participants in
      the hypocrisy condition wrote a public (personally identifiable) passage about
      the importance of a healthy lifestyle. The principal dependent measure was the
      intention to improve one's health behaviors. In both studies, self-esteem scores
      were positively related to intentions to change behavior in the hypocrisy
      condition but not in a control condition. The implications of these findings for
      conceptions of self-esteem and for dissonance theory are discussed.

PMID- 18331279
TI  - Differential stability and individual growth trajectories of big five and
      affective traits during young adulthood.
AB  - Big Five and affective traits were measured at three assessments when
      participants were on average 18, 21, and 24 years old. Rank-order stability
      analyses revealed that stability correlations tended to be higher across the
      second compared to the first retest interval; however, affective traits
      consistently were less stable than the Big Five. Median stability coefficients
      for the Big Five increased from .62 (Time 1 vs. Time 2) to .70 (Time 2 to Time
      3); parallel increases also were observed for measures of negative affectivity
      (median rs=.49 and .55, respectively) and positive affectivity (median rs=.48 and
      .57, respectively). Growth curve analyses revealed significant change on each of
      the Big Five and affective traits, although many of the scales also showed
      significant variability in individual trajectories. Thus, rank-order stability is
      increasing for a range of personality traits, although there also is significant
      variability in change trajectories during young adulthood.

PMID- 18331280
TI  - Stability and change in personality traits from late adolescence to early
      adulthood: a longitudinal twin study.
AB  - We conducted a longitudinal-biometric study examining stability and change in
      personality from ages 17 to 24 in a community sample of male and female twins.
      Using Tellegen's (in press) Multidimensional Personality Questionnaire (MPQ),
      facets of Negative Emotionality (NEM) declined substantially at the mean and
      individual levels, whereas facets of Constraint (CON) increased over time.
      Furthermore, individuals in late adolescence who were lowest on NEM and highest
      on CON remained the most stable over time, whereas those exhibiting the inverse
      profile (higher NEM, lower CON) changed the most in a direction towards growth
      and maturity. Analyses of gender differences yielded greater mean-level increases
      over time for women as compared to men on facets of CON and greater mean-level
      increases for men than women on facets of Agentic Positive Emotionality (PEM).
      Biometric analyses revealed rank-order stability in personality to be largely
      genetic, with rank-order change mediated by both the nonshared environment (and
      error) as well as genes. Findings correspond with prior evidence of a normative
      trend toward growth and maturity in personality during emerging adulthood.

PMID- 18331281
TI  - Understanding the search for meaning in life: personality, cognitive style, and
      the dynamic between seeking and experiencing meaning.
AB  - Although several theories assert that understanding the search for meaning in
      life is important, empirical research on this construct is sparse. Three studies
      provide the first extensive effort to understand the correlates of the search for
      meaning in a multistudy research program. Assessed were relations between search
      for meaning and well-being, cognitive style, and the Big Five, Big Three,
      Approach/Avoidance, and Interest models of personality, with a particular
      emphasis on understanding the correlates of search for meaning that are
      independent of presence of meaning. Conceptual models of the relation between
      search and presence were tested. Findings suggest that people lacking meaning
      search for it; the search for meaning did not appear to lead to its presence.
      Study 3 found that basic motive dispositions moderated relations between search
      for meaning and its presence. Results highlight the importance of basic
      personality dispositions in understanding the search for meaning and its
      correlates.

PMID- 18331282
TI  - Intergenerational transmission of values: family generativity and adolescents'
      narratives of parent and grandparent value teaching.
AB  - In this longitudinal study, we compared family stories told by 32 Canadian
      adolescents at ages 16 and 20 about how parents and grandparents had taught them
      values. Relations to parents' and children's levels of generativity were also
      examined. Adolescents' stories of grandparent value teaching were less readily
      recalled and less interactive in their content compared with stories about
      parents. Stories of value teaching by more generative parents were more likely to
      involve specific episodes, to be more interactive, to be more likely to emphasize
      caring content, and to be less likely to have their message rejected by the
      teens. Similarly, when parents were more generative, adolescents' stories about
      grandparents' value teaching were also more likely to involve specific and
      interactive episodes. Finally, stories told about parents and grandparents that
      were more positive on these dimensions predicted higher generative concern scores
      for the adolescents themselves, measured subsequently at age 24. Adolescents'
      stories about parent and grandparent socialization in more generative family
      contexts thus have features that suggest a more compelling process of
      intergenerational value transmission.

PMID- 18331283
TI  - Hypericum perforatum extract in burning mouth syndrome: a randomized placebo
      controlled study.
AB  - Burning mouth syndrome (BMS) or stomatodynia is characterized by a spontaneous
      burning pain in the oral mucosa without known cause or recognized treatment. This
      double-blind, randomized, placebo-controlled, single-center study evaluated the
      effects of systemic Hypericum perforatum extract in patients with BMS. Forty
      three patients participated, of whom 39 (35 women, four men, aged 64.9 +/- 4.7
      years) completed the study. The patients took indistinguishable 300-mg capsules
      containing either H. perforatum extract (hypericin 0.31% and hyperforin 3.0%) or
      placebo three times a day for 12 weeks. The intensity of burning pain was
      evaluated using a 10-cm visual analog scale (VAS) before the first dose and at
      visits after 4, 8, and 12 weeks. Furthermore, we also recorded the number of oral
      mucosa sites with reported burning symptoms and the self-reported descriptions of
      the patient's condition before and after the treatment. Pain, measured using the
      VAS, was similar at the beginning of the study and even though a slightly better
      performance in the test group, the difference was not statistically significant
      (P = 0.2216). The results failed to demonstrate that 300 mg of H. perforatum
      extract taken three times a day for 12 weeks improved the pain of BMS patients,
      although the general reduction in the number of sites with reported burning
      sensation, a less accurate and objective score, was significant.

PMID- 18331284
TI  - The management of oral mucous membrane pemphigoid with dapsone and topical
      corticosteroid.
AB  - STATEMENT OF PROBLEM: Mucous membrane pemphigoid (MMP) is a chronic autoimmune
      subepithelial disease that primarily affects the mucous membranes of patients
      over the age of 50 years, resulting in mucosal ulceration and subsequent
      scarring. PURPOSE: The purpose of this study was to investigate the efficacy of
      dapsone in combination with topical corticosteroids to treat the oral lesions of
      MMP. MATERIALS AND METHODS: Twenty-two patients who had been diagnosed with MMP
      were selected. The oral features were graded according to severity of disease
      from 1 to 3. Each patient was assigned to one of four groups according to his or
      her response to therapy. RESULTS: Five patients with mild to moderate disease
      were treated with topical corticosteroids alone for the duration of the study; 15
      patients with moderate to severe disease were treated by topical corticosteroid
      with dapsone therapy. All of 15 patients had significant benefits. CONCLUSIONS:
      The use of dapsone in combination with topical corticosteroids is one of the most
      useful methods for the treatment of MMP.

PMID- 18331285
TI  - Isolation and characterization of dental pulp stem cells from a supernumerary
      tooth.
AB  - BACKGROUND: Dental pulp stem cells (DPSCs) were primarily derived from the pulp
      tissues of primary incisors and permanent third molar teeth, whereas no report to
      our knowledge has yet been documented on deriving DPSCs from the other tooth
      types. The aim of this study is to present a novel approach of harvesting stem
      cells from a supernumerary tooth (a mesiodens). MATERIALS AND METHODS: The pulp
      tissues from a mesiodens of a 20-year-old healthy male patient and the left lower
      deciduous canine of a healthy 10-year-old boy (the positive control) were
      extracted and cultured for DPSCs, which were examined with stem cells (Oct-4,
      Nanog and Rex-1) and differentiation (Osteonectin and Nestin) markers.
      Furthermore, DPSCs were directionally differentiated to osteogenic and adipogenic
      cell lineages. RESULTS: Dental pulp stem cells derived from the mesiodens were
      capable of differentiating into adipogenic and osteogenic lineages. The
      mesioden's DPSCs also expressed stem cell and differentiation markers, which
      suggested their stem cell origin and differentiation capability. All the
      aforementioned results for the mesiodens were consistent with those of the DPSCs
      derived from the positive control. CONCLUSION: We have demonstrated the
      feasibility of deriving DPSCs from a usually discarded tissue such as a
      supernumerary tooth.

PMID- 18331286
TI  - Immunoexpression of hMSH2 and hMLH1 in oral squamous cell carcinoma and its
      relationship to histological grades of malignancy.
AB  - BACKGROUND: The aim of this study was to describe the human mutS homolog 2
      (hMSH2) and human mutL homolog 1 (hMLH1) immunoexpression in different areas of
      oral squamous cell carcinoma (OSCC) - central/superficial (C/S) and invasive
      tumor front (ITF) - in an attempt to verify if the histological grade of
      malignancy interferes in this expression. METHODS: Forty-six samples of OSCC were
      analyzed histologically. Twenty-six cases (56.5%) presented ITF. Histological
      grades of malignancy were evaluated in all samples, and immunohistochemistry was
      applied using specific antibodies against hMSH2 and hMLH1 proteins.
      Immunoexpression was semiquantitatively scored, and results were correlated with
      their histological grades of malignancy. RESULTS: The hMSH2 immunoexpression in
      both C/S and ITF was not correlated with histological grades of malignancy,
      whereas hMLH1 overexpression was correlated (P = 0.043) and associated (P =
      0.041) with well-differentiated tumors. In addition, hMHL1 reduction or negative
      expression was detected in poorly differentiated tumors. Moreover, negative
      expression for hMSH2 and hMLH1 proteins was demonstrated in some cases of OSCC.
      CONCLUSIONS: The findings of the present study indicate that the histological
      grade of malignancy interferes in hMLH1 immunoexpression. The negativity for both
      hMSH2 and hMLH1 proteins in some cases suggests a possible association between
      OSCC and hereditary non-polyposis colorectal cancer. Further investigation from
      future studies is needed to elucidate this supposition.

PMID- 18331287
TI  - Head and neck squamous cell carcinoma in non-smoking and non-drinking patients
      with multiple tumors: etiologic significance of p53 and Ki-67 in non-tumorous
      epithelium.
AB  - BACKGROUND: Non-smoking and non-drinking patients with head and neck squamous
      cell carcinoma have different clinical characteristics than their smoking and
      drinking counterparts. They are predominantly older female patients with oral
      cavity tumors, however, both groups show the same percentage of second primary
      tumors. Expression of tumor suppressor gene p53 and proliferation marker Ki-67 in
      mucosal epithelial cells was analyzed to study whether biomarker expression is
      associated with a history of smoking and drinking and with single and multiple
      tumors. METHODS: Non-smoking and non-drinking patients with multiple (n = 18) and
      single tumors (n = 15), smoking and drinking patients with multiple (n = 15) and
      single tumors (n = 14) were selected. For all groups, p53 and Ki-67 expression
      patterns in non-tumorous (tumor-adjacent) mucosa including positivity of
      dispersed single cells and clusters for p53 and for suprabasal expression of Ki
      67 were immunohistochemically analyzed and compared. RESULTS: p53 expression was
      significantly higher in users of tobacco and alcohol than in non-users. Ki-67
      expression was not affected by tobacco and alcohol usage. Both Ki-67 and p53 were
      similarly expressed in the groups with single and multiple tumors and hence not
      significantly related to the number of tumors. CONCLUSIONS: Non-smoking and non
      drinking patients with squamous cell carcinoma have the same risk for developing
      multiple tumors as their smoking and drinking counterparts. As this occurs
      without an increased expression of p53 or Ki-67, the significance of these
      proteins as biomarkers indicating pre-malignant mucosal alterations is doubtful.
      Further research is needed to clarify this predisposition for developing multiple
      head and neck cancer.

PMID- 18331288
TI  - Influences of tumor stroma on the malignant phenotype.
AB  - BACKGROUND: The microenvironment makes a significant contribution to the
      progression of oral carcinomas. Many different stromal events, such as
      vascularization, fibroblast activation, myofibroblast differentiation, and the
      presence of specific stromal proteins, such as proteolytic enzymes, fibronectin
      and laminin 5 are all characteristics of the tumor stroma. Less is, however,
      known of the significance of the biophysical properties of the tumor stroma. The
      purpose of the present study was to investigate how cellular and mechanical
      properties of the three-dimensional collagen matrix may influence cell
      proliferation and invasion of oral carcinoma cell lines. METHOD: Oral cancer
      cells were cultured in an organotypic culture system on different collagen
      concentrations, and invasion was measured. Furthermore, the presence of cancer
      associated proteins such as glycosylated oncofetal fibronectin and laminin 5 was
      investigated. RESULTS: We found that expression of glycosylated oncofetal
      fibronectin was increased in the invasive phenotype of oral carcinoma cell lines.
      Furthermore we demonstrated that certain concentrations of collagen in the
      connective tissue equivalent, appears to stimulate invasiveness of oral carcinoma
      cells.

PMID- 18331289
TI  - Regulated interactions of the norepineprhine transporter by the actin and
      microtubule cytoskeletons.
AB  - One role of the actin cytoskeleton is to maintain the structural morphology and
      activity of the pre-synaptic terminal. We sought to determine if the actin
      cytoskeleton plays a role in regulating interactions between the norepinephrine
      transporter (NET) and alpha-Synuclein (alpha-Syn), two proteins expressed in the
      pre-synaptic terminal. In cells transfected with either 0.5 microg/mL or 3
      microg/mL of alpha-Syn and 1 microg/mL of NET DNA, treatment with cytochalasin D,
      an actin depolymerizing agent, caused a dose-dependent decrease and increase,
      respectively, in [3H]-NE uptake. Protein interactions between NET, beta-actin,
      and alpha-Syn were modified, along with levels of surface transporters. Treatment
      of primary brainstem neurons and frontal cortex synaptosomes with cytochalasin D
      caused a 115% and 28% increase, respectively, in NET activity. Depolymerization
      of both actin and microtubules did not alter NET activity in cells with 0.5
      microg/mL alpha-Syn, but caused an increase in [3H]-NE uptake in cells
      transfected with 3 microg/mL of alpha-Syn and primary neurons. This is the first
      direct demonstration of NET activity being regulated via actin and modulated by
      interactions with alpha-Syn.

PMID- 18331290
TI  - Gene expression in the rat brain during prostaglandin D2 and adenosinergically
      induced sleep.
AB  - Previous studies have supported the hypothesis that macromolecular synthesis
      occurs in the brain during sleep as a response to prior waking activities and
      that prostaglandin D2 (PGD2) is an endogenous sleep substance whose effects are
      dependent on adenosine A2a receptor-mediated signaling. We compared gene
      expression in the cerebral cortex, basal forebrain, and hypothalamus during PGD2
      induced and adenosinergically-induced sleep to results from our previously
      published study of recovery sleep (RS) after sleep deprivation (SD). Immediate
      early gene expression in the cortex during sleep induced by PGD2- or by the
      selective adenosine A2a agonist CGS21680 showed limited similarity to that
      observed during RS while, in the basal forebrain and hypothalamus, widespread
      activation of immediate early genes not seen during RS occurred. In all three
      brain regions, PGD2 and CGS21680 reduced the expression of arc, a transcript
      whose expression is elevated during SD. Using GeneChips, the majority of genes
      induced by either PGD2 or CGS21680 were induced by both, suggesting activation of
      the same pathways. However, gene expression induced in the brain after PGD2 or
      CGS21680 treatment was distinct from that described during RS after SD and
      apparently involves glial cell gene activation and signaling pathways in neural
      immune interactions.

PMID- 18331291
TI  - Repair of right carotid artery pseudoaneurysm in a patient with hostile aortic
      arch through left ventricular approach.
AB  - We describe the case of an 81-year-old male who presented with a rapidly
      expanding neck hematoma from a common carotid artery pseudoaneurysm. Percutaneous
      repair using the right femoral artery approach was unsuccessful due to a hostile
      aortic arch. Using a small left thoracotomy and antegrade left ventricular access
      to the ascending aorta, a covered stent was successfully delivered at the site of
      the pseudoaneurysm. Our case provides proof-of-principle that complex carotid
      interventions can be performed expediently through a left ventricular approach in
      patients with hostile aortic arch.

PMID- 18331292
TI  - Essential role of choline for pneumococcal virulence in an experimental model of
      meningitis.
AB  - OBJECTIVES: The goal of the present study was to elucidate the contribution of
      the newly recognized virulence factor choline to the pathogenesis of
      Streptococcus pneumoniae in an animal model of meningitis. RESULTS: The choline
      containing strain D39Cho(-) and its isogenic choline-free derivative D39Cho(
      )licA64--each expressing the capsule polysaccharide 2--were introduced
      intracisternally at an inoculum size of 10(3) CFU into 11 days old Wistar rats.
      During the first 8 h post infection both strains multiplied and stimulated a
      similar immune response that involved expression of high levels of
      proinflammatory cytokines, the matrix metalloproteinase 9 (MMP-9), IL-10, and the
      influx of white blood cells into the CSF. Virtually identical immune response was
      also elicited by intracisternal inoculation of 10(7) CFU equivalents of either
      choline-containing or choline-free cell walls. At sampling times past 8 h strain
      D39Cho(-) continued to replicate accompanied by an intense inflammatory response
      and strong granulocytic pleiocytosis. Animals infected with D39Cho(-) died within
      20 h and histopathology revealed brain damage in the cerebral cortex and
      hippocampus. In contrast, the initial immune response generated by the choline
      free strain D39Cho(-)licA64 began to decline after the first 8 h accompanied by
      elimination of the bacteria from the CSF in parallel with a strong WBC response
      peaking at 8 h after infection. All animals survived and there was no evidence
      for brain damage. CONCLUSION: Choline in the cell wall is essential for
      pneumococci to remain highly virulent and survive within the host and establish
      pneumococcal meningitis.

PMID- 18331293
TI  - Do financial incentives of introducing case mix reimbursement increase feeding
      tube use in nursing home residents?
AB  - OBJECTIVES: To determine whether adoption of Medicaid case mix reimbursement is
      associated with greater prevalence of feeding tube use in nursing home (NH)
      residents. DESIGN: Secondary analysis of longitudinal administrative data about
      the prevalence of feeding tube insertion and surveys of states' adoption of case
      mix reimbursement. SETTING: NHs in the United States. PARTICIPANTS: NH residents
      at the time of NH inspection between 1993 and 2004. MEASUREMENTS: Facility
      prevalence of feeding tubes reported at the state inspection of NHs reported in
      the Online Survey, Certification and Reporting database and interviews with state
      policy makers regarding the adoption of case mix reimbursement. RESULTS: Between
      1993 and 2004, 16 states adopted Resource Utilization Group case mix
      reimbursement. States varied in the prevalence of feeding tubes in their NHs.
      Although the use of feeding tube increased substantially over the years of the
      study, once temporal trends and facility fixed effects were accounted for, case
      mix reimbursement was not associated with greater prevalence of feeding tube use.
      CONCLUSION: The adoption of Medicaid case mix reimbursement was not associated
      with an increase in the prevalence of feeding tube use.

PMID- 18331294
TI  - Residual urine as a risk factor for lower urinary tract infection: a 1-year
      follow-up study in nursing homes.
AB  - OBJECTIVES: To determine whether postvoid urine is a risk factor for the
      development of lower urinary tract infections (UTIs) in nursing home residents.
      DESIGN: Prospective surveillance with a follow-up period of 1 year. SETTING: Six
      Norwegian nursing homes. PARTICIPANTS: One hundred fifty nursing home residents.
      METHODS: Postvoid residual (PVR) urine volumes were measured using a portable
      ultrasound. UTIs were registered prospectively for 1 year. RESULTS: Ninety-eight
      residents (65.3%) had a PVR less than 100 mL, and 52 (34.7%) had a PVR of 100 mL
      or greater. During the follow-up period, 51 residents (34.0%) developed one or
      more UTIs. The prevalence of UTI in women was higher than in men (40.4% vs 19.6%;
      P=.02). There was no significant difference in mean PVR between residents who did
      and did not develop a UTI (79 vs 97 mL, P=.26). PVR of 100 mL or greater was not
      associated with greater risk of developing a UTI (P=.59). CONCLUSION: High PVR is
      common in nursing home residents. No association between PVR and UTI was found.

PMID- 18331295
TI  - Associations between vitamin D status and pain in older adults: the Invecchiare
      in Chianti study.
AB  - OBJECTIVES: To examine cross-sectional associations between vitamin D status and
      musculoskeletal pain and whether they differ by sex. DESIGN: Population-based
      study of persons living in the Chianti geographic area (Tuscany, Italy). SETTING:
      Community. PARTICIPANTS: Nine hundred fifty-eight persons (aged > or = 65)
      selected from city registries of Greve and Bagno a Ripoli. MEASUREMENTS: Pain was
      categorized as mild or no pain in the lower extremities and back; moderate to
      severe back pain, no lower extremity pain; moderate to severe lower extremity
      pain, no back pain; and moderate to severe lower extremity and back pain (dual
      region). Vitamin D was measured according to radioimmunoassay, and deficiency was
      defined as 25-hydroxyvitamin D (25(OH)D) less than 25 nmol/L. RESULTS: The mean
      age+/-standard deviation was 75.1+/-7.3 for women and 73.9+/-6.8 for men. Fifty
      eight percent of women had at least moderate pain in some location, compared with
      27% of men. After adjusting for potential confounders, vitamin D deficiency was
      not associated with lower extremity pain or dual-region pain, although it was
      associated with a significantly higher prevalence of at least moderate back pain
      without lower extremity pain in women (odds ratio=1.96, 95% confidence
      interval=1.01-3.59) but not in men. CONCLUSION: Lower concentrations of 25(OH)D
      are associated with significant back pain in older women but not men. Because
      vitamin D deficiency and chronic pain are fairly prevalent in older adults, these
      findings suggest it may be worthwhile to query older adults about their pain and
      screen older women with significant back pain for vitamin D deficiency.

PMID- 18331296
TI  - The positive financial contribution of home-based primary care programs: the case
      of the Mount Sinai Visiting Doctors.
AB  - The coming decade will see a rise in the number of homebound seniors. These
      vulnerable patients have great difficulty accessing primary care. Home-based
      primary care (HBPC) can fill this healthcare need. Presently, such programs have
      been slow to develop, in part because of the perception that they are fiscal
      liabilities. Using the Mount Sinai Visiting Doctors (MSVD) program, the total
      financial effect of an HBPC program on an Academic Health Center (AHC) was
      assessed. A retrospective cohort analysis (n=692, 565 patient years) of Medicare
      eligible individuals who were enrolled in the MSVD HBPC program was conducted.
      Revenues and associated costs for direct physician home care services, inpatient
      admissions, and outpatient clinic and emergency department visits for 1 calendar
      year were captured. Sensitivity analyses varying efficiency and cost variables
      were performed. Total direct cost for HBPC for the patient cohort was $976,350.
      Direct billing from home visits generated revenues that covered 24% of total
      direct care costs. Over a 12-month period, the cohort had 398 inpatient
      admissions and 1,100 non-HBPC outpatient visits, generating an overall
      contribution to margin of nearly $2.6 million. It is likely that this analysis
      underestimates the true contribution to margin, because it does not capture
      patient encounters at specialty clinics not in the Department of Medicine,
      unaffiliated medical centers, or private community-based practices. Although
      direct billing for HBPC programs does not generate enough revenue to meet
      operating costs, they can be significant revenue generators for the wider
      healthcare system and thus are fiscally worthy of subsidization.

PMID- 18331297
TI  - Quality of life in patients with facial steroid dermatitis before and after
      treatment.
AB  - BACKGROUND: Improper long-term, even low-dose, topical corticosteroids,
      especially application to the face, could induce steroid dermatitis, which was
      refractory and detrimental to the quality of life. OBJECTIVE: To evaluate the
      quality of life in patients with facial steroid dermatitis before and after the
      treatment of doxycycline and indomethacin plus support therapy. STUDY DESIGN: A
      prospective study. SETTING: Outpatients of the Department of dermatology, the
      Third Hospital of Hangzhou, from August 2, 2004, to April 20, 2005. SUBJECTS:
      Fifty consecutive outpatients completed the treatment. INTERVENTION: The
      intervention is doxycycline 10 mg twice a day and indomethacin 25 mg twice a day
      for 4 weeks, cetirizine or loratadine 10 mg daily if pruritic, topical white
      petroleum if feeling dry and wet dressing if burning and oedema, plus
      psychological support and health education. MAIN OUTCOME MEASURE: The efficacy of
      the treatment was quantified using a 24-point steroid clinical score. The
      detriment of the quality of life was quantified using a 30-point Dermatology Life
      Quality Index. RESULTS: The steroid dermatitis clinical score decreased
      significantly from 15.06 +/- 4.61 at baseline to 4.52 +/- 3.39 at 2 weeks after
      the end of treatment (week 6; P < 0.001). Twenty-one patients underwent a rebound
      phenomenon and the steroid dermatitis clinical score increased significantly from
      13.71 +/- 4.33 at baseline (week 0) to 19.24 +/- 3.40 at 1 week after treatment
      (week 1; P < 0.001). Quality of life score decreased significantly from 13.76 +/-
      7.68 at baseline to 3.44 +/- 2.57 at 2 weeks after the end of treatment (week 6;
      P < 0.001). CONCLUSIONS: The quality of life was profoundly affected by facial
      steroid dermatitis. Doxycycline and indomethacin plus support therapy might be
      effective in patients with facial steroid dermatitis.

PMID- 18331298
TI  - Novel frameshift mutation of the DSRAD gene in a Chinese family with
      dyschromatosis symmetrica hereditaria.

PMID- 18331299
TI  - Erythema gyratum repens-like eruption in mycosis fungoides: is dermatophyte
      superinfection underdiagnosed in cutaneous T-cell lymphomas?

PMID- 18331300
TI  - Leukocytoclastic vasculitis localized to one hemisoma in a human immunodeficiency
      virus-positive patient.

PMID- 18331301
TI  - Black hairy tongue associated with long-term oral erythromycin use.

PMID- 18331302
TI  - Paecilomyces lilacinus cutaneous infection associated with peripherally inserted
      central catheter insertion.

PMID- 18331303
TI  - Squamous cell carcinoma at tetanus vaccination site.

PMID- 18331304
TI  - Linear lichen planus distributed in the lines of Blaschko developing during
      intramuscular triamcinolone acetonide therapy for alopecia areata multiplex.

PMID- 18331305
TI  - Amantadine-induced livedo reticularis occurring during treatment of chronic
      hepatitis C.

PMID- 18331306
TI  - Temperament and character profile of patients with psoriasis.
AB  - BACKGROUND: Psychosocial factors have been implicated as being important in the
      onset and/or exacerbation of psoriasis.(1) The aim of this study is to examine
      both the personality factors of patients with psoriasis and the correlations
      between temperament and character dimensions. MATERIAL AND METHODS: A total
      number of 105 psoriasis patients and 109 healthy individuals were enrolled in the
      study. Questionnaires including Beck Depression Inventory (BDI), Beck Anxiety
      Inventory (BAI), and Temperament and Character Inventory (TCI) were administered
      individually. Both groups were evaluated in terms of depression, anxiety and
      characteristic features by using these psychological tests and compared
      statistically. The relationship between psoriasis area and severity index (PASI)
      score and the BDI, BAI and TCI scales were also evaluated. RESULTS: The mean BDI
      score of the psoriasis group were significantly higher than the control group.
      The psoriasis group had significantly higher scores of harm avoidance and lower
      scores of being self-directedness than the control group. The duration of
      psoriasis and the PASI scores were not correlated with BDI and BAI scores.
      CONCLUSION: The current study shows that psoriasis patients have distinctive
      temperament and character dimensions when compared with the control group. We
      suggest that evaluation and treatment of psoriasis should also include
      psychosomatic approaches in clinical practice.

PMID- 18331307
TI  - Hair darkening after treatment with cyclosporin in a patient with psoriasis.

PMID- 18331308
TI  - Linea fusca in a male adolescent successfully treated with azelaic acid.

PMID- 18331309
TI  - A fixed drug eruption that developed cross-sensitivity among amide local
      anaesthetics, including mepivacaine hydrochloride, lidocaine hydrochloride and
      propitocaine hydrochloride.

PMID- 18331310
TI  - Recalcitrant vulvar lichen sclerosis treated with aminolevulinic acid
      photodynamic therapy: a report of five cases.

PMID- 18331311
TI  - Macadamia nut allergy.

PMID- 18331312
TI  - Pectoralis major myocutaneous flap in the treatment of a dermatofibrosarcoma
      protuberans.

PMID- 18331313
TI  - Disaccharide analysis of skin glycosaminoglycan in lichen myxedematosus.

PMID- 18331314
TI  - Comparison of vulvar skin diseases in black and white women: a histopathological
      study.

PMID- 18331315
TI  - Personalized medicine: a world of opportunities in skin diseases.

PMID- 18331317
TI  - Chromomycosis--successful CO2 laser vaporization.

PMID- 18331316
TI  - An infant with juvenile xanthogranuloma, multiple cafe-au-lait macules, acute
      myeloid leukaemia: an incomplete, rare form of triple association?

PMID- 18331318
TI  - Clinicopathologic profile of normocomplementemic and hypocomplementemic
      urticarial vasculitis: a study from South India.
AB  - BACKGROUND: This study aims to study the clinical and histopathological
      characteristics of hypocomplementemic and normocomplementemic urticarial
      vasculitis (HUVS and NUV) among dermatology clinic attendees in a tertiary care
      hospital in South India. PATIENTS AND METHODS: A prospective study was conducted
      in the dermatology department from February 2003 to May 2004. Seventy-five
      patients met the inclusion criteria for UV. Sixty-eight patients in whom
      complement levels were available were classified into either NUV or HUVS groups.
      Clinical features, laboratory parameters and histological features were compared,
      and the significance of differences was established using Pearson's Chi-squared
      test. RESULTS: There was a female preponderance among patients with HUVS. Wheals
      > 24 h were seen in 90% of patients, and in 54.4% of patients, the wheals were
      partially blanching or non-blanching. Angioedema was more prevalent in patients
      with NUV than HUVS (44.4% vs. 21.4%). Systemic involvement was seen in 64.3% of
      patients with HUVS and 44.4% of patients with NUV. Fever, ANA positivity and
      systemic lupus erythematosus (SLE) were significantly associated with HUVS. In
      most cases of UV, a provoking factor could not be identified. Neutrophilic small
      vessel vasculitis was seen in 42.9% of patients with HUVS and 16.6% patients with
      NUV. Direct immunofluorescence test showing immunoreactants at the dermo
      epidermal junction were present in 60% of patients with HUVS and 33.3% patients
      with NUV. CONCLUSION: The clinical features of Indian patients with UV were
      similar to those reported from the West. Fever, ANA positivity and SLE were
      significantly associated with HUVS.

PMID- 18331319
TI  - Oral manifestations of adverse drug reactions: guidelines.
AB  - BACKGROUND: Adverse drug reactions are noxious and unintended responses to a
      medicinal product. Many drugs have the potential to induce adverse reactions in
      the mouth. The extent of such reactions is unknown; however, because a lot of
      them are asymptomatic, many are believed to go unnoticed. Adverse oral drug
      reactions are responsible for oral lesions and manifestations that can mime local
      or systemic disease. Their pathogenesis, especially of the mucosal reactions, is
      largely unknown and appears to involve complex interactions between the drug in
      question, other medications, the patient's underlying disease, genetics and
      lifestyle factors. AIM: In this study, we have listed the principal signs and
      symptoms of oral and perioral adverse drug reactions and the responsible drugs.
      Diagnosis for adverse drug reaction is not easy given also the limited utility of
      laboratory tests. The association between a drug and an adverse drug reaction is
      mostly based on the disappearance of the reactions following discontinuance of
      the offending drug. Sometimes, it is useful to perform rechallenge tests
      reintroducing the drug to establish cause and effect. CONCLUSIONS: Knowledge of
      adverse drug-induced oral effects helps health professionals to better diagnose
      oral disease, administer drugs and improve patient compliance during drug therapy
      and may foster a more rational use of drugs.

PMID- 18331320
TI  - Psoriasis and diabetes: a population-based cross-sectional study.
AB  - BACKGROUND: Previous reports have shown an association between psoriasis and the
      metabolic syndrome, but there are only a few studies on the association between
      psoriasis and diabetes. OBJECTIVES: To study the association between psoriasis
      and diabetes. METHODS: A cross-sectional study was performed utilizing the
      database of Clalit Health Services (CHS). Patients who were diagnosed with
      psoriasis were compared with CHS enrolees without psoriasis regarding the
      prevalence of diabetes. Patients with diabetes were identified using the CHS
      chronic diseases registry. Chi-squared tests were used to compare categorical
      parameters. Logistic regression models were used for multivariate analyses.
      RESULTS: The study included 16 851 patients with psoriasis and 74 987 subjects
      without psoriasis (control patients). The proportion of diabetes was
      significantly higher in patients above 35 years (P < 0.05). The age-adjusted
      proportion of diabetes was significantly higher in psoriasis patients as compared
      to the control group [odds ratio (OR), 1.38, P < 0.05] and was similar in men and
      women (OR, 1.32, 1.45, respectively). A multivariate logistic regression model
      showed that psoriasis was significantly associated with diabetes, independently
      of age and gender (OR, 1.58, P < 0.001). CONCLUSIONS: Our study supports previous
      reports of an association between psoriasis and diabetes. Dermatologists taking
      care of patients with psoriasis should be aware of this association and advise
      the patients to reduce additional risk factors such as smoking, hypertension or
      dyslipidemia.

PMID- 18331321
TI  - Efficacy of botulinum toxin for a congenital eccrine naevus.

PMID- 18331322
TI  - Long-term efficacy of etanercept in hidradenitis suppurativa.

PMID- 18331323
TI  - Becker's melanosis superimposed on acquired superficial angimatosis.

PMID- 18331324
TI  - Acne inversa of the anogenital region: early radical surgical excision with
      plastic defect coverage is treatment of choice.

PMID- 18331325
TI  - Developing an instrument for evaluating implementation of clinical practice
      guidelines: a test-retest study.
AB  - RATIONALE AND AIMS: This study focuses on the development of an instrument for
      the evaluation of clinical practice guidelines and is one part of a research
      project about the implementation and use of such guidelines among hospitals in
      the southern region of Sweden. The aim of the present paper was to investigate
      the test-retest reliability of a questionnaire. METHOD: A questionnaire was
      designed to gather data about guidelines that have been implemented as well as
      information about factors, which, according to the Promoting Action on Research
      Implementation in Health Services (PARIHS)-model, influence the success of
      implementation. Thirty-nine health professionals at one of the hospitals included
      in the survey completed the questionnaire on two occasions within a mean time of
      5.5 weeks. The test-retest reliability was analysed by means of Cohen's Kappa and
      percentage concordance. RESULTS: Eight items had good agreement in terms of
      strength and high percentage concordance. With regard to the Kappa values, 13
      items show moderate and two fair agreement. CONCLUSIONS: The test-retest
      reliability scores show mainly acceptable results indicating a reasonable
      stability, thus suggesting the possibility of further developing the instrument.
      The factors described in the PARIHS-model seem relevant for use in evaluating
      implementation and use of guidelines. The instrument could benefit from a
      revision of the language in order to enhance clarity and make it less abstract.

PMID- 18331326
TI  - Specific Fab fragments recovered by phage display technique recognizing human
      spermatozoa.
AB  - Human hybridoma cell lines are often unstable and loose ability for antibody
      production. Sometimes, they show low and varying levels of heavy and light chains
      synthesis. Therefore it is reasonable to preserve generated specificities of
      light and heavy chains by cloning them to phagemid vector and creating phage
      display library. The aim of this study was to construct phage display library of
      Fab fragments recognizing sperm surface antigens. The source of mRNA constituted
      seven hybridoma cell lines producing antisperm antibodies which was proved by
      ELISA, and agglutination test as well as by inhibition of sperm to penetrate
      hamster oocytes. Fragments of cDNA encoding kappa/lambda and gamma chains were
      cloned into pComb3HSS phagemid vector and amplified in XL-1Blue. The library was
      panned against whole unfixed sperm cells. Three positive clones selected after
      fourth round of panning showed heavy chain belonging to VH4 family, two of them
      (G28, K61) possessed lambda chain from VL2 family and one (H43) kappa chain from
      VK1 family. As these Fabs revealed similarities to antibodies against some
      proteins involved in sperm motility and cell fusion it can be suggested that
      these Fabs may be a cause of infertility. Finally, we proved that it is feasible
      to preserve specificities produced by human hybridomas using phage display
      technique and we recovered some Fabs which may be of diagnostic and research
      value, and may also have some value for contraceptive vaccine.

PMID- 18331327
TI  - Tracing ground water input to base flow using sulfate (S, O) isotopes.
AB  - Sulfate (S and O) isotopes used in conjunction with sulfate concentration provide
      a tracer for ground water contributions to base flow. They are particularly
      useful in areas where rock sources of contrasting S isotope character are
      juxtaposed, where water chemistry or H and O isotopes fail to distinguish water
      sources, and in arid areas where rain water contributions to base flow are
      minimal. Sonoita Creek basin in southern Arizona, where evaporite and igneous
      sources of sulfur are commonly juxtaposed, serves as an example. Base flow in
      Sonoita Creek is a mixture of three ground water sources: A, basin ground water
      with sulfate resembling that from Permian evaporite; B, ground water from the
      Patagonia Mountains; and C, ground water associated with Temporal Gulch. B and C
      contain sulfate like that of acid rock drainage in the region but differ in
      sulfate content. Source A contributes 50% to 70%, with the remainder equally
      divided between B and C during the base flow seasons. The proportion of B
      generally increases downstream. The proportion of A is greatest under drought
      conditions.

PMID- 18331328
TI  - Analytical methods for transient flow to a well in a confined-unconfined aquifer.
AB  - Concurrent existence of confined and unconfined zones of an aquifer can arise
      owing to ground water withdrawal by pumping. Using Girinskii's potential
      function, Chen (1974, 1983) developed an approximate analytical solution to
      analyze transient ground water flow to a pumping well in an aquifer that changes
      from an initially confined system to a system with both unconfined and confined
      regimes. This article presents the details of the Chen model and then compares it
      with the analytical model developed by Moench and Prickett (1972) for the same
      problem. Hypothetical pumping test examples in which the aquifer undergoes
      conversion from confined to water table conditions are solved by the two
      analytical models and also a numerical model based on MODFLOW. Comparison of the
      results suggests that the solutions of the Chen model give better results than
      the Moench and Prickett model except when the radial distance is very large or
      aquifer thickness is large compared with drawdown.

PMID- 18331329
TI  - Implications of rate-limited mass transfer for aquifer storage and recovery.
AB  - Pressure to decrease reliance on surface water storage has led to increased
      interest in aquifer storage and recovery (ASR) systems. Recovery efficiency,
      which is the ratio of the volume of recovered water that meets a predefined
      standard to total volume of injected fluid, is a common criterion of ASR
      viability. Recovery efficiency can be degraded by a number of physical and
      geochemical processes, including rate-limited mass transfer (RLMT), which
      describes the exchange of solutes between mobile and immobile pore fluids. RLMT
      may control transport behavior that cannot be explained by advection and
      dispersion. We present data from a pilot-scale ASR study in Charleston, South
      Carolina, and develop a three-dimensional finite-difference model to evaluate the
      impact of RLMT processes on ASR efficiency. The modeling shows that RLMT can
      explain a rebound in salinity during fresh water storage in a brackish aquifer.
      Multicycle model results show low efficiencies over one to three ASR cycles due
      to RLMT degrading water quality during storage; efficiencies can evolve and
      improve markedly, however, over multiple cycles, even exceeding efficiencies
      generated by advection-dispersion only models. For an idealized ASR model where
      RLMT is active, our simulations show a discrete range of diffusive length scales
      over which the viability of ASR schemes in brackish aquifers would be hindered.

PMID- 18331330
TI  - CONSID: a toolbox for contaminant source identification.
AB  - Model-based contaminant source identification plays an important role in
      effective site remediation. In this article, a contaminant source identification
      toolbox (CONSID) is introduced as a framework for solving contaminant source
      identification problems. It is known that the presence of various types of model
      uncertainties can severely undermine the performance of many existing source
      estimators. The current version of CONSID consists of two robust estimators for
      recovering source release histories under model uncertainty; one was developed in
      the deterministic framework and the other in the stochastic framework. To use the
      robust estimators provided in CONSID, the user is required to have only modest
      prior knowledge about the model uncertainty and be able to estimate the bound of
      model deviations resulting from the uncertainty. The toolbox is designed so that
      other source estimators can be added easily. A step-by-step guidance for using
      CONSID is described and an example is provided.

PMID- 18331331
TI  - Non-pathogenic commensal Escherichia coli bacteria can inhibit degranulation of
      mast cells.
AB  - BACKGROUND: The mast cell's (MC) ability to rapidly release presynthesized
      mediators allows it to play a critical role in the immune system's first-line
      response to pathogens. Although recent research has illuminated the role of MCs
      in bacterial infection, little is known about how non-pathogenic bacteria
      influence MC responses. OBJECTIVE: To characterize the influence of non
      pathogenic Escherichia coli bacteria on MCs. RESULTS: High concentrations of live
      E. coli strongly down-modulated the degranulation of murine peritoneal MCs under
      all activator conditions. Bacteria did not induce MC degranulation by themselves,
      and staining of MCs showed they were still entirely viable. Dead bacteria and
      bacterial supernatant had no effect on MC degranulation. Ex vivo experiments
      confirmed that E. coli exposure down-modulates subsequently induced MC
      degranulation and that this effect lasts for up to a few days after exposure.
      CONCLUSION: Our results show that high doses of non-pathogenic E. coli bacteria
      can function as a strong, direct inhibitor of MC degranulation. This suggests a
      possible basis for future antiallergic treatment or prophylaxis with commensal
      bacteria, i.e. probiotics.

PMID- 18331332
TI  - The silver locus product (Silv/gp100/Pmel17) as a new tool for the analysis of
      melanosome transfer in human melanocyte-keratinocyte co-culture.
AB  - Melanosomes are melanocyte-specific lysosome-related organelles that are
      transferred to keratinocytes of the epidermis and anagen hair bulb. Transferred
      melanin forms supra-nuclear caps that protect epidermal keratinocytes against UV
      irradiation. The mechanism(s) responsible for melanosome transfer into
      keratinocytes and their subsequent intra-keratinocyte distribution has long
      remained one of the most enigmatic of heterotypic cell interactions. Although
      there have been many attempts to study this process, significant progress has
      been hindered by the absence of an adequate in vitro model. During our ongoing
      study of melanocyte-keratinocyte interactions in skin and hair follicle, we have
      developed a novel in vitro assay that exploits the specificity of
      Silv/Pmel17/gp100 expression for melanosome/melanin granules. Using matched
      cultures of keratinocytes and melanocytes isolated from normal healthy epidermis
      together with double immunofluorescence, we have determined that gp100 is a
      surprisingly useful tracker of transferred melanin. Moreover, transferred gp100
      stained melanin granules emit a bright fluorescence signal, facilitating ready
      quantification of melanin transfer levels between melanocytes and keratinocytes.
      This quantitative approach was validated using known inducers and inhibitors of
      the melanocyte phenotype. This assay further confirmed that cytophagocytosis of
      melanocyte components (e.g. dendrite tips) by keratinocytes is one route for
      melanin incorporation into keratinocytes. Lastly, a role for the recently
      proposed filopodium as a direct conduit for melanin transfer was substantiated
      using this novel approach. In conclusion, this assay promises to significantly
      aid our investigations of the molecular basis of melanosome transfer and offers a
      new tool for the clinical evaluation of melanocyte modulators.

PMID- 18331333
TI  - The skin as a biofactory for systemic secretion of erythropoietin: potential of
      genetically modified keratinocytes and fibroblasts.
AB  - BACKGROUND: The skin is an interesting target tissue for gene therapy
      applications because of its ready accessibility. One possibility would be to
      utilize the genetically modified skin as a biofactory secreting a systemically
      needed product, such as erythropoietin (EPO). METHODS: Keratinocytes (KC) and
      fibroblasts (FB) were transduced with a retroviral vector encoding human EPO.
      Gene transfer efficiency was assessed by real-time PCR analysis and flow
      cytometry of transduced cells. In addition, EPO synthesis and secretion were
      analysed by quantifying the amount of RNA and secreted protein in both monolayer
      cultures and skin equivalents (SE). RESULTS: When cultured as a monolayer, EPO-KC
      synthesized significantly more EPO than EPO-FB, as shown by quantitatively
      measuring the amount of secreted protein and RNA. This correlated with an
      increased EPO-vector incorporation in KC compared with FB, demonstrated by
      determining both the percentage of transduced cells and the average transgene
      copy number per cell. In addition, in transduced cell cultures enriched to
      equally high percentages of EPO+ cells, KC showed a higher activity of EPO
      secretion than FB. Finally, when assembled in a SE, EPO-KC secreted significantly
      higher amounts of EPO than EPO-FB, although reduced secretory activity of EPO-KC
      monolayers grown in high calcium concentrations suggested that in stratified
      epidermis differentiated KC secrete less EPO than non-differentiated KC.
      CONCLUSION: In summary, while both transduced KC and FB are able to synthesize
      and secrete human EPO, KC show higher potential in serving as possible target
      cells for therapeutic substitution with EPO, probably because of improved
      transduction rates and increased secretory activity.

PMID- 18331334
TI  - Fluorescence in situ hybridization (FISH) analysis of the interactions between
      honeybee larvae and Paenibacillus larvae, the causative agent of American
      foulbrood of honeybees (Apis mellifera).
AB  - American foulbrood (AFB) is a bacterial disease of honeybee larvae caused by the
      spore-forming bacterium Paenibacillus larvae. Although AFB and its aetiological
      agent are described now for more than a century, the general and molecular
      pathogenesis of this notifiable disease is poorly understood. We used
      fluorescence in situ hybridization (FISH) performed with P. larvae-specific, 16S
      rRNA-targeted oligonucleotide probes to analyse the early steps in the
      pathogenesis of American foulbrood. The following chain of events could be
      demonstrated: (i) the spores germinate in the midgut lumen, (ii) the vegetative
      bacteria massively proliferate within the midgut before, and (iii) they start to
      locally breach the epithelium and invade the haemocoel. The paracellular route
      was shown to be the main mechanism for invasion contrasting earlier hypotheses of
      phagocytosis of P. larvae. Invasion coincided with the death of the host
      implicating that the penetration of the midgut epithelium is a critical step
      determining the time of death.

PMID- 18331335
TI  - Pseudomonas aeruginosa strain RW41 mineralizes 4-chlorobenzenesulfonate, the
      major polar by-product from DDT manufacturing.
AB  - Pseudomonas aeruginosa RW41 is the first bacterial strain, which could be
      isolated by virtue of its capability to mineralize 4-chlorobenzenesulfonic acid
      (4CBSA), the major polar by-product of the chemical synthesis of 1,1,1-trichloro
      2,2-bis-(4-chlorophenyl)ethane (DDT). This capability makes the isolate a
      promising candidate for the development of bioremediation technologies. The
      bacterial mineralization of 4CBSA proceeds under oxygenolytic desulfonation and
      transient accumulation of sulfite which then is oxidized to sulfate. High enzyme
      activities for the turnover of 4-chlorocatechol were measured. The further
      catabolism proceeded through 3-chloromuconate and, probably, the instable 4
      chloromuconolactone, which is directly hydrolyzed to maleylacetate. Detectable
      levels of maleylacetate reductase were only present when cells were grown with
      4CBSA. When the ordinary catechol pathway was induced during growth on
      benzenesulfonate, catechol was ortho-cleaved to cis,cis-muconate and a partially
      purified muconate cycloisomerase transformed it to muconolactone in vitro. The
      same enzyme transformed 3-chloro-cis,cis-muconate into cis-dienelactone (76%) and
      the antibiotically active protoanemonin (24%). These observations are indicative
      for a not yet highly evolved catabolism for halogenated substrates by bacterial
      isolates from environmental samples which, on the other hand, are able to
      productively recycle sulfur and chloride ions from synthetic
      haloorganosulfonates.

PMID- 18331336
TI  - Halophilic Archaea determined from geothermal steam vent aerosols.
AB  - Hydrothermal vents, known as 'fumaroles', are ubiquitous features of geothermal
      areas. Although their geology has been extensively characterized, little is known
      about the subsurface microbial ecology of fumaroles largely because of the
      difficulty in collecting sufficient numbers of cells from boiling steam water for
      DNA extraction and culture isolation. Here we describe the first collection,
      molecular analysis and isolation of microbes from fumarole steam waters in Russia
      (Kamchatka) and the USA (Hawaii, New Mexico, California and Wyoming).
      Surprisingly, the steam vent waters from all the fumaroles contained halophilic
      Archaea closely related to the Haloarcula spp. found in non-geothermal salt mats,
      saline soils, brine pools and salt lakes around the world. Microscopic cell
      counting estimated the cell dispersal rate at approximately 1.6 x 10(9) cells
      year(-1) from a single fumarole. We also managed to enrich microbes in high-salt
      media from every vent sample, and to isolate Haloarcula from a Yellowstone vent
      in a 20% salt medium after a month-long incubation, demonstrating both salt
      tolerance and viability of cells collected from high-temperature steam.
      Laboratory tests determined that microbes enriched in salt media survived
      temperatures greater than 75 degrees C for between 5 and 30 min during the
      collection process. Hawaiian fumaroles proved to contain the greatest diversity
      of halophilic Archaea with four new lineages that may belong to uncultured
      haloarchaeal genera. This high diversity may have resulted from the leaching of
      salts and minerals through the highly porous volcanic rock, creating a chemically
      complex saline subsurface.

PMID- 18331337
TI  - How to get more out of molecular fingerprints: practical tools for microbial
      ecology.
AB  - Community-level molecular techniques are widely used in comparative microbial
      ecology to assess the diversity of microbial communities and their response to
      changing environments. These include among others denaturing and temperature
      gradient gel electrophoresis (DGGE/TGGE), single-strand conformation polymorphism
      (SSCP), length heterogeneity-PCR (LH-PCR), terminal-restriction fragment length
      polymorphism (tRFLP) and 16S rRNA gene clone libraries. The amount of data
      derived from these techniques available in literature is continuously increasing
      and the lack of a universal way to interpret the raw fingerprint itself makes it
      difficult to compare between different results. Taking the DGGE technique as an
      example, we propose a setting-independent theoretical interpretation of the DGGE
      pattern, based on a straightforward processing on three levels of analysis: (i)
      the range-weighted richness (Rr) reflecting the carrying capacity of the system,
      (ii) the dynamics (Dy) reflecting the specific rate of species coming to
      significance, and (iii) functional organization (Fo), defined through a relation
      between the structure of a microbial community and its functionality. These Rr,
      Dy and Fo values, each representing a score to describe a microbial community,
      can be plotted in a 3D graph. The latter represents a visual ecological
      interpretation of the initial raw fingerprinting pattern.

PMID- 18331338
TI  - The histamine H1-receptor mediates the motivational effects of novelty.
AB  - Novelty-induced arousal has motivational effects and can reinforce behavior. The
      mechanisms by which novelty acts as a reinforcer are unknown. Novelty-induced
      arousal can be either rewarding or aversive dependent on its intensity and the
      preceding state of arousal. The brain's histamine system has been implicated in
      both arousal and reinforcement. Histamine and histamine-1-receptor (H1R) agonists
      induced arousal and wakefulness in humans and rodents, e.g. by stimulating
      cortical acetylcholine (ACh) release. The H1R has also been implicated in
      processes of brain reward via interactions with the nigrostriatal- and mesolimbic
      dopamine (DA) systems. We asked whether the motivational effects of novelty
      induced arousal are compromised in H1R knockout (KO) mice. The H1R-KO mice failed
      to develop a conditioned place-preference induced by novel objects. Even though
      they still explore novel objects, their reinforcing value is diminished.
      Furthermore, they showed impaired novelty-induced alternation in the Y-maze.
      Rearing activity and emotional behavior in a novel environment was also altered
      in H1R-KO mice, whereas object-place recognition was unaffected. The H1R-KO mice
      had higher ACh concentrations in the frontal cortex and amygdala (AMY). In the
      latter, the H1R-KO mice had also increased levels of DA, but a lower
      dihydrophenylacetic acid/DA ratio. Furthermore, the H1R-KO mice had also
      increased tyrosine hydroxylase immunoreactivity in the basolateral anterior,
      basolateral ventral and cortical AMY nuclei. We conclude that the motivational
      effects of novelty are diminished in H1R-KO mice, possibly due to reduced novelty
      induced arousal and/or a dysfunctional brain reward system.

PMID- 18331339
TI  - Endogenous opioids inhibit ischemia-induced generation of immature hippocampal
      neurons via the mu-opioid receptor.
AB  - It is established that hippocampal neurogenesis is dynamically regulated by
      physiological and pathological stimuli including learning, environmental
      complexity, mental disorders and brain lesion. Little is known about factors
      regulating adaptive changes in neurogenesis. Using mu-opioid receptor (MOP)
      knockout mice we addressed whether endogenous opioids influence ischemia-induced
      enhancement of hippocampal neurogenesis. Permanent middle cerebral artery
      occlusion (MCAO) produced similar corticostriatal infarcts in MOP-knockout and
      wildtype mice. Analyses of BrdU/doublecortin-colabelled cells in the granule cell
      layer 14 days after MCAO showed that ischemic knockouts contained more immature
      neurons generated during days 9-11 than wildtypes. After 29 days, similar
      quantities of BrdU/NeuN-labelled cells were found in ischemic knockout and
      wildtype mice, suggesting that granule cells that were formed in excess during
      days 9-11 in the knockouts were eliminated by day 29. Neurogenesis was similar in
      knockout and wildtype mice subjected to sham operation. In addition to a
      transient increase in neurogenesis, MCAO caused a transient up-regulation of
      preprodynorphin and preproenkephalin mRNA expression in the granule cell layer.
      Our findings suggest that activated signalling via endogenous opioids and the MOP
      limits the enhanced generation of neuronal cells after ischemic corticostriatal
      lesions.

PMID- 18331340
TI  - D2 dopamine modulation of corticoaccumbens synaptic responses changes during
      adolescence.
AB  - Dopaminergic afferents from the ventral tegmental area (VTA) modulate information
      processing in the nucleus accumbens (NA), a brain region critical for motivation
      and reward mechanisms. In NA medium spiny neurons (MSNs) from young rats, D(2)
      agonists have been shown to decrease the amplitude of corticoaccumbens synaptic
      responses. As several dopamine-related functions change during adolescence, we
      assessed the D(2) modulation of cortical inputs with whole-cell recordings in
      slices obtained from adult and preadolescent rats. The D(2) agonist quinpirole (5
      microM) decreased synaptic response of NA MSNs to electrical cortical stimulation
      in slices from preadolescent rats. In slices from adult rats, however, quinpirole
      increased both the amplitude of evoked synaptic responses and the frequency of
      spontaneous synaptic events. These effects were blocked by the GABA-A antagonist
      picrotoxin (50 microM), revealing a D(2)-mediated decrease These results suggest
      that D(2) receptors modulate NA neurons differently in young and adult rats, due
      to the emergence of a D(2)-facilitated GABA component in corticoaccumbens
      responses during adolescence.

PMID- 18331341
TI  - Imbalance between excitation and inhibition among synaptic connections of CA3
      pyramidal neurons in cultured hippocampal slices.
AB  - A fundamental property of small neuronal ensembles is their ability to be
      selectively activated by distinct stimuli. One cellular mechanism by which
      neurons achieve this input selectivity is by modulating the temporal dynamics of
      excitation and inhibition. We explored the interplay of excitation and inhibition
      in synapses between pyramidal neurons of cornu ammonis field 3 of the hippocampal
      formation (CA3) in cultured rat hippocampal slices, where activation of a single
      excitatory cell can readily recruit local interneurons. Simultaneous whole-cell
      recordings from pairs of CA3 pyramidal neurons revealed that the strength of
      connections was neither uniform nor balanced. Rather, stimulation of presynaptic
      neurons elicited distinct combinations of excitatory postsynaptic current
      inhibitory postsynaptic current (EPSC-IPSC) amplitudes in the postsynaptic
      neurons. EPSC-IPSC sequences with small EPSCs had large IPSCs and sequences that
      contained large EPSCs had small IPSCs. In addition to differences in the
      amplitudes of the responses, the kinetics of the EPSCs were also different,
      creating distinct temporal dynamics of excitation and inhibition. Weaker EPSCs
      had significantly slower kinetics and were efficiently occluded by IPSCs, thereby
      further limiting their contribution to depolarizing the postsynaptic membrane.
      Our data suggest that hippocampal pyramidal cells may use an imbalance between
      excitation and inhibition as a filter to enhance selectivity toward preferential
      excitatory connections.

PMID- 18331342
TI  - Perinatal protein restriction reduces the inhibitory action of serotonin on food
      intake.
AB  - Early malnutrition has been associated with a high risk of developing obesity,
      diabetes and cardiovascular diseases in adulthood. In animals, poor perinatal
      nutrition produces hyperphagia and persistent increased levels of serotonin (5
      HT) in the brain. Inasmuch as 5-HT is directly related to the negative regulation
      of food intake, here we have investigated whether the anorexic effects of 5-HT
      are altered by protein malnutrition. Pregnant Sprague-Dawley rats were fed ad
      libitum either a control (20% protein) or a low-protein (8% protein) diet
      throughout pregnancy and lactation. At weaning, pups received a standard diet and
      at 35 days their feeding behaviour was evaluated after the administration of DL
      fenfluramine (DL-FEN), an anorexic compound that blocks the reuptake of 5-HT and
      stimulates its release. Male offspring born to protein-restricted dams exhibited
      significantly decreased body weight and hyperphagia compared with controls. DL
      FEN dose-dependently reduced the 1 h chow intake at the onset of the dark cycle
      in both control and undernourished rats. However, the hypophagic effects of DL
      FEN were significantly attenuated in animals submitted perinatally to protein
      restriction. The stimulatory action of DL-FEN on c-fos immunoreactivity within
      the paraventricular nucleus of the hypothalamus was also decreased in low-protein
      fed rats. Further pharmacological analysis with selective 5-HT(1B) and 5-HT(2C)
      receptor agonist showed that the reduced anorexic effects of 5-HT in malnourished
      animals were coupled to a desensitization of 5-HT(1B) receptors. These
      observations indicate that the hyperphagia associated with metabolic programming
      is at least partially related to a reduced regulatory function of 5-HT on food
      intake.

PMID- 18331343
TI  - Bone morphogenetic protein signaling in the developing kidney: present and
      future.
AB  - Bone morphogenetic proteins (BMPs) are members of the transforming growth factor
      beta superfamily. A critical role for BMP signaling in the development of the
      metanephric kidney is supported by a growing number of studies using in vitro
      assays and in vivo animal models. Here we review current knowledge of BMPs, BMP
      receptors and regulators of the BMP signaling pathway in the developing kidney.
      We highlight major gaps in our knowledge of the roles of BMP signaling in the
      development of the normal and abnormal kidney and identify areas and techniques
      likely to improve our understanding.

PMID- 18331344
TI  - Modulation of amyloid-beta aggregation and toxicity by inosose stereoisomers.
AB  - Amyloid-beta (Abeta) aggregation and amyloid formation are key pathological
      features of Alzheimer's disease, and are considered to be two of the major
      contributing factors to neurodegeneration and dementia. Identification of small
      molecule inhibitors that are orally available, have low toxicity and high central
      nervous system bioavailability is one approach to the potential development of a
      disease-modifying treatment for Alzheimer's disease. We have previously
      identified inositol stereoisomers as exhibiting stereospecific inhibition of
      Abeta aggregation and toxicity in vitro and in vivo. We report here the effects
      of inosose versus inositol stereoisomers on Abeta fibrillogenesis as determined
      using CD and fluorescence spectroscopy and negative-stain electron microscopy.
      The inososes differ from inositols by the oxidation of one of the hydroxyl groups
      to a ketone. These molecules help in the further elucidation of the structure
      activity relationships of inositol-Abeta interactions and identify both allo
      inositol and epi-2-inosose as in vitro inhibitors of Abeta aggregation.

PMID- 18331345
TI  - SUMOylation of the hepatoma-derived growth factor negatively influences its
      binding to chromatin.
AB  - Hepatoma-derived growth factor is a nuclear targeted mitogen containing a PWWP
      domain that mediates binding to DNA. To date, almost nothing is known about the
      molecular mechanisms of the functions of hepatoma-derived growth factor, its
      routes of secretion and internalization or post-translational modifications. In
      the present study, we show for the first time that hepatoma-derived growth factor
      is modified by the covalent attachment of small ubiquitin-related modifier 1
      (SUMO-1), a post-translational modification with regulatory functions for an
      increasing number of proteins. Using a basal SUMOylation system in Escherichia
      coli followed by a MALDI-TOF-MS based peptide analysis, we identified the lysine
      residue SUMOylated located in the N-terminal part of the protein adjacent to the
      PWWP domain. Surprisingly, this lysine residue is not part of the consensus motif
      described for SUMOylation. With a series of hepatoma-derived growth factor
      mutants, we then confirmed that this unusual location is also used in mammalian
      cells and that SUMOylation of hepatoma-derived growth factor takes place in the
      nucleus. Finally, we demonstrate that SUMOylated hepatoma-derived growth factor
      is not binding to chromatin, in contrast to its unSUMOylated form. These
      observations potentially provide new perspectives for a better understanding of
      the functions of hepatoma-derived growth factor.

PMID- 18331346
TI  - Epigenetics: the study of embryonic stem cells by restriction landmark genomic
      scanning.
AB  - During mammalian development, it is essential that the proper epigenetic state is
      established across the entire genome in each differentiated cell. To date, little
      is known about the mechanism for establishing epigenetic modifications of
      individual genes during the course of cellular differentiation. Genome-wide DNA
      methylation analysis of embryonic stem cells by restriction landmark genomic
      scanning provides information about cell type- and tissue-specific DNA
      methylation profiles at tissue-specific methylated regions associated with
      developmental processes. It also sheds light on DNA methylation alterations
      following fetal exposure to chemical agents. In addition, analysis of embryonic
      stem cells deficient in epigenetic regulators will contribute to revealing the
      mechanism for establishing DNA methylation profiles and the interplay between DNA
      methylation and other epigenetic modifications.

PMID- 18331347
TI  - Epigenetics: differential DNA methylation in mammalian somatic tissues.
AB  - Epigenetics refers to heritable phenotypic alterations in the absence of DNA
      sequence changes, and DNA methylation is one of the extensively studied
      epigenetic alterations. DNA methylation is an evolutionally conserved mechanism
      to regulate gene expression in mammals. Because DNA methylation is preserved
      during DNA replication it can be inherited. Thus, DNA methylation could be a
      major mechanism by which to produce semi-stable changes in gene expression in
      somatic tissues. Although it remains controversial whether germ-line DNA
      methylation in mammalian genomes is stably heritable, frequent tissue-specific
      and disease-specific de novo methylation events are observed during somatic cell
      development/differentiation. In this minireview, we discuss the use of
      restriction landmark genomic scanning, together with in silico analysis, to
      identify differentially methylated regions in the mammalian genome. We then
      present a rough overview of quantitative DNA methylation patterns at 4600 NotI
      sites and more than 150 differentially methylated regions in several C57BL/6J
      mouse tissues. Comparative analysis between mice and humans suggests that some,
      but not all, tissue-specific differentially methylated regions are conserved. A
      deeper understanding of cell-type-specific differences in DNA methylation might
      lead to a better illustration of the mechanisms behind tissue-specific
      differentiation in mammals.

PMID- 18331348
TI  - Epigenetics: application of virtual image restriction landmark genomic scanning
      (Vi-RLGS).
AB  - Restriction landmark genomic scanning (RLGS) is a powerful method for the
      systematic detection of genetic mutations in DNA length and epigenetic alteration
      due to DNA methylation. However, the identification of polymorphic spots is
      difficult because the resulting RLGS spots contain very little target DNA and
      many non-labeled DNA fragments. To overcome this, we developed a virtual image
      restriction landmark genomic scanning (Vi-RLGS) system to compare actual RLGS
      patterns with computer-simulated RLGS patterns (virtual RLGS patterns). Here, we
      demonstrate in detail the contents of the simulation program (rlgssim), based on
      the linear relationship between the reciprocal of mobility plotted against DNA
      fragment length and Vi-RLGS profiling of Arabidopsis thaliana.

PMID- 18331349
TI  - Epigenetics: use of in silico genome scanning by the virtual image restriction
      landmark method.

PMID- 18331351
TI  - Interaction and functional association of protein disulfide isomerase with
      alphaVbeta3 integrin on endothelial cells.
AB  - Adhesive properties of endothelial cells are influenced by the thioldisulfide
      balance. However, the molecular mechanism of this effect is unclear, although
      recent observations indicate that integrin receptors may be direct targets for
      redox modulation. The purpose of this study was to examine whether protein
      disulfide isomerase (PDI) is directly involved in this process. As manganese ions
      are known to affect the thioldisulfide balance and activate integrins to maximal
      affinity, we searched for PDI interactions with integrins, particularly with
      alpha(V)beta(3), in Mn(2+)-treated endothelial cells. By employing confocal
      microscopy, flow cytometry and coimmunoprecipitation experiments, we showed that
      exposure of endothelial cells to Mn(2+) resulted in: (a) the appearance of
      surface protein thiol groups, which can be found in PDI and alpha(V)beta(3), and
      both proteins colocalizing on the cellular surface; and (b) the formation of the
      PDI-alpha(V)beta(3) complex, which dissociates upon reduction. In addition, PDI
      in a complex with alpha(V)beta(3) induces conversion of the integrin to the
      ligand-competent high-affinity state, as evidenced by increased binding of
      vitronectin. The membrane-impermeable sulfhydryl blockers 3-N-maleimidylpropionyl
      biocytin 3-N-maleimidylpropionyl biocytin and p-chloromercuriphenyl sulfonate, as
      well as the PDI inhibitors bacitracin, MA3 018, and MA3 019, abolished the
      binding of vitronectin and LM609 to endothelial cells that is activated by
      Mn(2+). Consistently, LM609 almost completely blocked binding of vitronectin to
      such cells. The formation of the PDI-alpha(V)beta(3) stoichiometric complex was
      further demonstrated by surface plasmon resonance analysis, which showed that the
      initial reversible binding of PDI becomes irreversible in the presence of Mn(2+),
      probably mediated by disulfide bonds. Thus, we show that Mn(2+) simultaneously
      modulates the thiol isomerase activity of PDI that is bound to alpha(V)beta(3)
      and induces its transition to the ligand-competent state, suggesting an
      alternative mechanism of integrin regulation.

PMID- 18331352
TI  - Cholesterol interaction with the related steroidogenic acute regulatory lipid
      transfer (START) domains of StAR (STARD1) and MLN64 (STARD3).
AB  - The steroidogenic acute regulatory (StAR)-related lipid transfer (START) domains
      are found in a wide range of proteins involved in intracellular trafficking of
      cholesterol and other lipids. Among the START proteins are the StAR protein
      itself (STARD1) and the closely related MLN64 protein (STARD3), which both
      function in cholesterol movement. We compared the cholesterol-binding properties
      of these two START domain proteins. Cholesterol stabilized STARD3-START against
      trypsin-catalyzed degradation, whereas cholesterol had no protective effect on
      STARD1-START. [(3)H]Azocholestanol predominantly labeled a 6.2 kDa fragment of
      STARD1-START comprising amino acids 83-140, which contains residues proposed to
      interact with cholesterol in a hydrophobic cavity. Photoaffinity labeling studies
      suggest that cholesterol preferentially interacts with one side wall of this
      cavity. In contrast, [(3)H]azocholestanol was distributed more or less equally
      among the polypeptides of STARD3-START. Overall, our results provide evidence for
      differential cholesterol binding of the two most closely related START domain
      proteins STARD1 and STARD3.

PMID- 18331353
TI  - CYP7B1-mediated metabolism of dehydroepiandrosterone and 5alpha-androstane
      3beta,17beta-diol--potential role(s) for estrogen signaling.
AB  - CYP7B1, a cytochrome P450 enzyme, metabolizes several steroids involved in
      hormonal signaling including 5alpha-androstane-3beta,17beta-diol (3beta-Adiol),
      an estrogen receptor agonist, and dehydroepiandrosterone, a precursor for sex
      hormones. Previous studies have suggested that CYP7B1-dependent metabolism
      involving dehydroepiandrosterone or 3beta-Adiol may play an important role for
      estrogen receptor beta-mediated signaling. However, conflicting data are reported
      regarding the influence of different CYP7B1-related steroids on estrogen receptor
      beta activation. In the present study, we investigated CYP7B1-mediated
      conversions of dehydroepiandrosterone and 3beta-Adiol in porcine microsomes and
      human kidney cells. As part of these studies, we compared the effects of 3beta
      Adiol (a CYP7B1 substrate) and 7alpha-hydroxy-dehydroepiandrosterone (a CYP7B1
      product) on estrogen receptor beta activation. The data obtained indicated that
      3beta-Adiol is a more efficient activator, thus lending support to the notion
      that CYP7B1 catalysis may decrease estrogen receptor beta activation. Our data on
      metabolism indicate that the efficiencies of CYP7B1-mediated hydroxylations of
      dehydroepiandrosterone and 3beta-Adiol are very similar. The enzyme catalyzed
      both reactions at a similar rate and the K(cat)/K(m) values were in the same
      order of magnitude. A high dehydroepiandrosterone/3beta-Adiol ratio in the
      incubation mixtures, similar to the ratio of these steroids in many human
      tissues, strongly suppressed CYP7B1-mediated 3beta-Adiol metabolism. As the
      efficiencies of CYP7B1-mediated hydroxylation of dehydroepiandrosterone and 3beta
      Adiol are similar, we propose that varying steroid concentrations may be the most
      important factor determining the rate of CYP7B1-mediated metabolism of
      dehydroepiandrosterone or 3beta-Adiol. Consequently, tissue-specific steroid
      concentrations may have a strong impact on CYP7B1-dependent catalysis and thus on
      the levels of different CYP7B1-related steroids that can influence estrogen
      receptor beta signaling.

PMID- 18331354
TI  - Light regulation of CaS, a novel phosphoprotein in the thylakoid membrane of
      Arabidopsis thaliana.
AB  - Exposure of Arabidopsis thaliana plants to high levels of light revealed specific
      phosphorylation of a 40 kDa protein in photosynthetic thylakoid membranes. The
      protein was identified by MS as extracellular calcium-sensing receptor (CaS),
      previously reported to be located in the plasma membrane. By confocal laser
      scanning microscopy and subcellular fractionation, it was demonstrated that CaS
      localizes to the chloroplasts and is enriched in stroma thylakoids. The
      phosphorylation level of CaS responded strongly to light intensity. The light
      dependent thylakoid protein kinase STN8 is required for CaS phosphorylation. The
      phosphorylation site was mapped to the stroma-exposed Thr380, located in a motif
      for interaction with 14-3-3 proteins and proteins with forkhead-associated
      domains, which suggests the involvement of CaS in stress responses and signaling
      pathways. The knockout Arabidopsis lines revealed a significant role for CaS in
      plant growth and development.

PMID- 18331355
TI  - The amyloplast proteome of potato tuber.
AB  - Potato (Solanum tuberosum) is the fourth largest crop worldwide in yield, and cv.
      Kuras is the major starch potato of northern Europe. Storage starch is packed
      densely in tuber amyloplasts, which become starch granules. Amyloplasts of soil
      grown mini-tubers and agar-grown micro-tubers of cv. Kuras were purified. The
      mini-tuber amyloplast preparation was enriched 10-20-fold and the micro-tuber
      amyloplast approximately fivefold over comparative total protein extracts.
      Proteins separated by SDS-PAGE were digested with trypsin, analysed by mass
      spectrometry and identified by mascot software searches against an in-house
      potato protein database and the NCBI non-redundant plant database. The
      differential growth conditions for mini- and micro-tubers gave rise to rather
      different protein profiles, but the major starch granule-bound proteins were
      identical for both and dominated by granule-bound starch synthase I, starch
      synthase II and alpha-glucan water dikinase. Soluble proteins were dominated by
      starch phosphorylase L-1, other large proteins of the classes 'starch and sucrose
      metabolism', 'pentose phosphate pathway', 'glycolysis', 'amino acid metabolism',
      and other proteins such as plastid chaperonins. The majority of the identified
      proteins had a predicted plastid transit peptide, supporting their presence in
      the amyloplast. However, several highly expressed proteins had no transit
      peptide, such as starch phosphorylase H, or had a predicted mitochondrial
      location. Intriguingly, all polyphenol oxidases, a family of enolases, one
      transketolase, sulfite reductase, deoxynucleoside kinase-like and dihydroxy-acid
      dehydrase had twin-arginine translocation motifs, and a homologue to
      dihydrolipoamide dehydrogenase had a Sec (secretory) motif; these motifs usually
      target thylakoid-like structures.

PMID- 18331356
TI  - The complex of the insect LDL receptor homolog, lipophorin receptor, LpR, and its
      lipoprotein ligand does not dissociate under endosomal conditions.
AB  - The insect low-density lipoprotein (LDL) receptor (LDLR) homolog, lipophorin
      receptor (LpR), mediates endocytic uptake of the single insect lipoprotein, high
      density lipophorin (HDLp), which is structurally related to LDL. However, in
      contrast to the fate of LDL, which is endocytosed by LDLR, we previously
      demonstrated that after endocytosis, HDLp is sorted to the endocytic recycling
      compartment and recycled for re-secretion in a transferrin-like manner. This
      means that the integrity of the complex between HDLp and LpR is retained under
      endosomal conditions. Therefore, in this study, the ligand-binding and ligand
      dissociation capacities of LpR were investigated by employing a new flow
      cytometric assay, using LDLR as a control. At pH 5.4, the LpR-HDLp complex
      remained stable, whereas that of LDLR and LDL dissociated. Hybrid HDLp-binding
      receptors, containing either the beta-propeller or both the beta-propeller and
      the hinge region of LDLR, appeared to be unable to release ligand at endosomal
      pH, revealing that the stability of the complex is imparted by the ligand-binding
      domain of LpR. The LpR-HDLp complex additionally appeared to be EDTA-resistant,
      excluding a low Ca(2+) concentration in the endosome as an alternative trigger
      for complex dissociation. From binding of HDLp to the above hybrid receptors, it
      was inferred that the stability upon EDTA treatment is confined to LDLR type A
      (LA) ligand-binding repeats 1-7. Additional (competition) binding experiments
      indicated that the binding site of LpR for HDLp most likely involves LA-2-7. It
      is therefore proposed that the remarkable stability of the LpR-HDLp complex is
      attributable to this binding site. Together, these data indicate that LpR and
      HDLp travel in complex to the endocytic recycling compartment, which constitutes
      a key determinant for ligand recycling by LpR.

PMID- 18331357
TI  - Functional domains of the human epididymal protease inhibitor, eppin.
AB  - Eppin has two potential protease inhibitory domains: a whey acid protein or four
      disulfide core domain and a Kunitz domain. The protein is also reported to have
      antibacterial activity against Gram-negative bacteria. Eppin and its whey acid
      protein and Kunitz domains were expressed in Escherichia coli and their ability
      to inhibit proteases and kill bacteria compared. The Kunitz domain inhibits
      elastase (EC 3.4.21.37) to a similar extent as intact eppin, whereas the whey
      acid protein domain has no such activity. None of these fragments inhibits
      trypsin (EC 3.4.21.4) or chymotrypsin (EC 3.4.21.1) at the concentrations tested.
      In a colony forming unit assay, both domains have some antibacterial activity
      against E. coli, but this was not to the same degree as intact eppin or the two
      domains together. When bacterial respiratory electron transport was measured
      using a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide
      assay, eppin and its domains caused an increase in the rate of respiration. This
      suggests that the mechanism of cell killing may be partly through the
      permeablization of the bacterial inner membrane, resulting in uncoupling of
      respiratory electron transport and consequent collapse of the proton motive
      force. Thus, we conclude that although both of eppin's domains are involved in
      the protein's antibacterial activity, only the Kunitz domain is required for
      selective protease inhibition.

PMID- 18331358
TI  - hhLIM is a novel F-actin binding protein involved in actin cytoskeleton
      remodeling.
AB  - Human heart LIM protein (hhLIM) is a newly cloned protein. In vitro analyses
      showed that green fluorescent protein (GFP)-tagged hhLIM protein accumulated in
      the cytoplasm of C2C12 cells and colocalized with F-actin, indicating that hhLIM
      is an actin-binding protein in C2C12 cells. Overexpression of hhLIM-GFP in C2C12
      cells significantly stabilized actin filaments and delayed depolymerization of
      the actin cytoskeleton induced by cytochalasin B treatment. Expression of hhLIM
      GFP in C2C12 cells also induced significant changes in the organization of the
      actin cytoskeleton, specifically, fewer and thicker actin bundles than in control
      cells, suggesting that hhLIM functions as an actin-bundling protein. This
      hypothesis was confirmed using low-speed co-sedimentation assays and direct
      observation of F-actin bundles that formed in vitro in the presence of hhLIM.
      hhLIM has two LIM domains. To identify the essential regions and sites for
      association, a series of truncated mutants was constructed which showed that LIM
      domain 2 has the same activity as full-length hhLIM. To further characterize the
      binding sites, the LIM domain was functionally destructed by replacing cysteine
      with serine in domain 2, and results showed that the second LIM domain plays a
      central role in bundling of F-actin. Taken together, these data identify hhLIM as
      an actin-binding protein that increases actin cytoskeleton stability by promoting
      bundling of actin filaments.

PMID- 18331359
TI  - Eubacterium plautii infection in a kidney transplant recipient: a noteworthy case
      of pleural effusion and fever.
AB  - We report a noteworthy case of Eubacterium plautii infection after kidney
      transplantation. Our 33-yr-old transplant recipient received standard care; his
      post-transplant course was uneventful. However, on day 44 he underwent an
      emergency laparotomy for perforation of the ileum. He was initially treated with
      ceftazidime, fluconazole and metronidazole, but his fever persisted, so he was
      switched to meropenem and vancocin. We could not find any cause for his
      infection. On day 70, his temperature normalized. On day 75, he developed severe
      leukopenia (280 cell/mL). His cytomegalovirus-DNA test result was negative, so
      all immunosuppressants, except for prednisone, were stopped; instead, antibiotic
      prophylaxis was started, using caspofungin, trimethoprim-sulfamethoxazole and
      ciprofloxacin. On day 83, he underwent percutaneous drainage of massive left
      pleural effusion. We repeatedly cultured the pleural liquid, but it was not till
      three wk later that we were finally able to identify the causative organism. We
      hypothesize that the microorganism - which normally resides on the surface of the
      intestinal lumen - entered the bloodstream via bacterial translocation,
      eventually colonizing the pleurae. This translocation was favored by our patient
      poor clinical condition, his immunosuppressive treatment and his heavy
      antibiotherapy. Our experience highlights the need for wiser use of antibiotics
      in transplant recipients.

PMID- 18331360
TI  - 'My pupil has gone black!' Subluxation of a total cataractous lens.
AB  - A patient with a history of longstanding opaque cataract and a white pupil
      reported a return to a black pupil, which was the result of lens subluxation. The
      case was complicated by optic nerve coloboma of the Morning Glory syndrome type
      and a total retinal detachment.

PMID- 18331361
TI  - Growth of the lens: in vitro observations.
AB  - Understanding the normal functioning of the human lens and its role in the
      development of disorders of vision, such as presbyopia and cataract, requires a
      thorough knowledge of how the lens grows and how its properties change with age.
      Many of these properties can be obtained only by studying the isolated organ in
      vitro. In addition, because of the difficulties in obtaining human tissues,
      animal lenses are frequently used as models for the human lens. Information is
      needed for these as well. In this review, current knowledge of lens growth and
      factors that affect growth are examined in a variety of species. Topics covered
      include changes in lens weight, dimensions, stiffness and refractive index
      distribution with age and the influence of other factors such as gender,
      environment and body size. From these, it has become clear that lens growth is
      not greatly affected by external influences. Although there are many similarities
      in the growth of lenses from different species, humans (and probably all
      primates) have distinctly different growth patterns, with prenatal and postnatal
      growth having different regulatory mechanisms. As a result, human lens properties
      are different from those of other species. Unfortunately, many of the published
      data are unreliable, presumably because of post-mortem changes, making it
      difficult to extrapolate in vitro observations to the in vivo situation.

PMID- 18331362
TI  - A new method of measuring lens refractive index.
AB  - A new clinical method for determining the refractive index of a lens is
      described. By measuring lens power in air and then immersing the lens in a liquid
      of known refractive index (n), it is possible to calculate the refractive index
      of the lens material (micro) by using the formula: micro = (nK (v,1) - K(v,n))/(K
      (v,1) - K (v,n)) where K (v,1) is the lens power determined in air K (v,n) is the
      lens power determined in the immersion liquid. The only materials required are a
      digital lensmeter and a wet cell for holding the lens in a liquid. The
      theoretical basis of the method is explained and a description given of the
      limitations. The optimal method of measuring different types of lenses is
      discussed. Sources of error include the thin lens theory behind the method, the
      use of a wetcell and the digital lensmeter. The theoretical accuracy of the
      results is given as 0.02 but 0.01 is usually achieved. In all cases, measuring
      the front vertex powers (FVP) yields a more accurate estimate of refractive index
      of a lens than measuring back vertex power (BVP). The author found half the
      lenses measured attained values within 0.005 of the known material index. This
      method is usually sufficiently accurate to isolate which lens material has been
      used in manufacturing and permit manufacturing spectacles that mimic the
      appearance of an earlier pair. Some suggestions for further refinement are given.

PMID- 18331363
TI  - Non-immediate reactions to beta-lactams: diagnostic value of skin testing and
      drug provocation test.
AB  - BACKGROUND: beta-Lactam (BL) antibiotics can induce non-immediate skin reactions,
      frequently manifested as exanthema or urticaria. The time between drug intake and
      the reaction appearance is generally 24-48 h. Because the mechanisms involved are
      not completely understood, diagnostic tests for these reactions have still to be
      fully validated. OBJECTIVE: To evaluate the role of skin and drug provocation
      tests (DPTs) in the diagnosis of patients with non-immediate reactions to BL.
      METHODS: We evaluated a group of 22 patients who developed maculopapular
      exanthema or urticarial exanthema after BL intake. Diagnosis was confirmed by DPT
      with BL. Intradermal/patch testing was performed with benzylpenicilloyl, minor
      determinant mixture, amoxicillin (AX), ampicillin (AMP) and the culprit drug in
      patients and in 22 negative controls. Immunohistochemical studies were done in
      the affected skin at the acute phase of the reaction and after a delayed positive
      skin test/DPT. IFN-gamma and IL-4 were quantified in peripheral mononuclear
      cells, obtained during the positive response to DPT and after resolution of the
      symptoms. RESULTS: From the total number of cases, 12 patients developed
      urticarial exanthema and 10 maculopapular exanthema after DPT. Only two of the 22
      patients (9%) had a positive delayed intradermal skin test: one to AX/AMP and the
      other to cloxacillin. Biopsies showed a mononuclear CD4, CD8 infiltrate and
      activated and memory cells. The cytokine expression showed a Th1 pattern in
      patients, in contrast with the Th0 pattern in controls. CONCLUSION: In patients
      with non-immediate reactions to BLs (maculopapular exathema or urticarial
      exanthema), the sensitivity of skin testing is low and DPT may be required to
      establish the diagnosis. The reproducibility of the reactions and the cytokine
      pattern expressed during the acute episode support a T cell-induced non-immediate
      response.

PMID- 18331364
TI  - Comparison of two basophil activation markers CD63 and CD203c in the diagnosis of
      amoxicillin allergy.
AB  - BACKGROUND: To confirm allergy to beta-lactam (BL), a basophil activation test in
      flow cytometry based on CD63 up-regulation was described. CD203c is a more recent
      basophil activation marker and up to day there is no consensus about which marker
      is the more sensitive one. CD203c has not yet been evaluated in the diagnosis of
      BL allergy. OBJECTIVE: The aim of the study was to compare the reliability of
      CD203c to CD63 for the diagnosis of amoxicillin (AX) allergy, which is nowadays
      the most frequent BL allergy. METHODS: Twenty-seven patients with an immediate
      positive skin test (ST) to AX, 20 had had anaphylaxis with AX and 7 had urticaria
      and/or angioedema, were compared with 14 controls with no allergy to BL and to
      six patients with delayed positive ST to AX. RESULTS: In the anaphylaxis group,
      AX induced up-regulation of CD203c in the basophils of 12 patients out of 20
      (60%) and of CD63 in four patients (20%) (P<0.02). Two patients out of seven with
      urticaria or angioedema had a positive result with CD203c and CD63. In patients
      who had anaphylaxis, ampicillin (AMP) induced CD203c up-regulation in eight out
      of 12 (67%) patients tested, and CD63 up-regulation in 4 out of 12 (33%) (all
      patients who had anaphylaxis could not be tested with AMP). False-positive
      results were observed with CD203c as well as CD63, and for 10 patients indeed
      this was confirmed by a negative drug provocation test. The origin of conflicting
      results between CD63 and CD203c might be at least the targeting of basophils
      based on anti-IgE labelling. Among IgE(+) gated cells, by means of CD33, a marker
      of monocytes, a contamination up to 50% by monocytes was detected. In contrast to
      CD63, CD203c is an activation marker specific of basophils with a basal low-level
      expression in resting basophils. Thus, IgE and CD203c double targeting of
      basophils avoids the contamination by monocytes. CONCLUSION: CD203c seems to be a
      more sensitive activation marker of basophils than CD63 for the diagnosis of
      amoxicillin allergy.

PMID- 18331365
TI  - Pleural effusions in patients with chronic myeloid leukaemia treated with
      dasatinib may have an immune-mediated pathogenesis.

PMID- 18331366
TI  - Hypoechoic thyroid nodules on ultrasound 4 years after prenatal exposure to
      radioiodine: resolution with thyroxine therapy.
AB  - We describe an infant inadvertently exposed to radioiodine at 17 weeks gestation.
      His mother had received 400 MBq of (131)I for hyperthyroidism (total T4 178
      nmol/L, thyroid stimulating hormone (TSH) <0.1 mU/L, 4-h (131)I uptake 16%).
      Following cordocentesis at 27 weeks (free T4 12.7 pmol/L, TSH 35.4 mU/L) intra
      amniotic thyroxine was withheld and a male infant was born at 39 weeks gestation,
      birthweight 3520 g. Cord TSH was low (0.1 mU/L), total T4 151 nmol/L on day 4,
      the mother having received no medication during pregnancy. Postnatal follow-up
      showed mild TSH elevation (11.0-19.4 mU/L) but normal free T4 (9-12.7 pmol/L)
      during the first 2 years of life following which the child was discharged still
      untreated. On recall at 4.3 years, TSH elevation persisted (15.4 mU/L) and
      ultrasound showed several hypoechoic thyroid nodules within the left lobe that
      disappeared after thyroxine treatment. CONCLUSION: In the event of inadvertent
      exposure to radioiodine in utero, the infant should receive thyroxine therapy
      from birth in order to protect the thyroid gland from TSH over-stimulation,
      however mild.

PMID- 18331367
TI  - Intellectual outcome, motor skills and BMI of children with congenital
      hypothyroidism: a population-based study.
AB  - AIM: To evaluate intellectual outcome, motor skills and anthropometric data of
      children with congenital hypothyroidism (CH). METHODS: Children with permanent CH
      who were born in 1999 in Bavaria were eligible for this prospective, population
      based study. Cognitive performance was evaluated by the Kaufman Assessment
      Battery for Children and motor skills were assessed by the motor test,
      Motoriktest fur vier-bis sechsjahrige Kinder (MOT) 4-6. RESULTS: Eighteen of 21
      eligible children participated (86%). Median age of the children was 5.5 years
      (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2
      days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean
      intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD]
      10.1): no children had IQ values below the normal range. Reactivity and speed of
      movement were significantly reduced in children with CH. Children with an initial
      thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly
      worse than children with TSH value of <or=200 mU/L (p=0.003). Children with CH
      had a significant increased risk for overweight (risk ratio [RR] 3.91, 95%
      confidence interval [CI] 1.22-11.75, p=0.005) compared to the Bavarian reference
      children. CONCLUSION: In this study, children with CH had an increased prevalence
      of overweight compared to reference data. Partially impaired motor skills could
      be shown, whereas the intellectual development was normal.

PMID- 18331368
TI  - Neonatal testicular torsion--a lost cause?
AB  - Twenty-four neonates presented with signs of testicular ischaemia over a 13-year
      period. They had a mean birth weight of 3.706 kg. The right testicle was affected
      in 13, the left in 9 and there was bilateral torsion in 2 babies. Two babies had
      no twist in the cord, but the testicles were nonviable macroscopically and
      microscopically. Twenty-one babies had primary exploration revealing necrotic
      testes in all patients and they underwent orchidectomies. The other three babies
      had conservative management and the affected testes had atrophied on follow-up.
      Sixteen babies had contralateral orchidopexy. Doppler ultrasound scans were
      reported as normal in 2 of 13 babies who had scans. No testes were salvaged
      following surgery. CONCLUSION: The incidence of testicular torsion in the
      neonatal period was calculated as 6.1 per 100,000 live births. No testis was
      salvaged following surgery in our series of 24 patients. This dismal outcome
      underlines that immediate surgical exploration, although commonly performed,
      rarely saves torted testes.

PMID- 18331369
TI  - Protracted 'anti-addictive' effects of adolescent phenylpropanolamine exposure in
      C57BL/6J mice.
AB  - Exposure to the once highly prevalent over-the-counter (OTC) sympathomimetic
      phenylpropanolamine (PPA; +/--norephedrine) during pre-adolescence alters the
      developmental trajectory of catecholamine and amino acid neurotransmitter systems
      in the nucleus accumbens (NAC) that culminate in a 'pro-addictive' phenotype in
      adulthood. Thus, the present study sought to extend these earlier data by
      examining the long-term consequences of repeated PPA treatment during adolescence
      upon the behavioral and neurochemical responses to cocaine. For this, C57BL/6J
      mice were pre-treated with PPA (0-40 mg/kg) during postnatal days 35-44, and the
      capacity of cocaine (4 x 15 mg/kg) to elicit a conditioned place-preference, as
      well as behavioral and neurochemical sensitization within the NAC, were then
      assessed in adulthood. While adolescent PPA exposure did not influence
      spontaneous locomotor activity or the motor responses to either acute or repeated
      cocaine (4 x 15 mg/kg), PPA pre-exposure dose-dependently reduced the expression
      of a conditioned place-preference. As observed previously for juvenile PPA
      treatment, adolescent PPA administration blunted the dopamine and norepinephrine
      response to acute cocaine, prevented the development of catecholamine
      sensitization but did not influence cocaine-induced elevations in serotonin.
      However, unlike juvenile PPA treatment, adolescent PPA also prevented the
      development of glutamate sensitization within the NAC. These data provide
      evidence that adolescent exposure to a formerly prevalent OTC sympathomimetic
      produces protracted effects upon cocaine-induced changes in NAC glutamate
      transmission that may reduce vulnerability to cocaine addiction in later life and
      further the hypothesis that early exposure to sympathomimetic drugs may be an
      environmental factor contributing to the etiology of addiction.

PMID- 18331370
TI  - Cocaine craving is associated with electrophysiological brain responses to
      cocaine-related stimuli.
AB  - Several studies show that substance dependence disorders are characterized by an
      enhanced processing of substance-related stimuli. The present study was designed
      to examine the association between craving levels and selective processing of
      drug cues in cocaine-dependent patients using event-related brain potentials
      (ERPs). In abstinent cocaine-dependent patients and a healthy control group, we
      studied the late positive potential (LPP) amplitudes elicited by neutral and
      cocaine-related stimuli. The results show that cocaine-dependent patients have an
      enhanced electrophysiological response in the late LPP time window to cocaine
      related stimuli as compared to controls, suggesting an enhanced processing of
      these stimuli. Most importantly, a robust association was observed between
      cocaine craving and LPP amplitude. High craving levels were associated with
      larger LPP amplitudes at central electrode sites in the right hemisphere. These
      findings are in line with theories linking motivational aspects and appetitive
      stimulus processing. Furthermore, it is demonstrated that ERPs are a useful index
      to assess motivational properties of stimuli in cocaine-dependent patients. These
      findings suggest that electrophysiological measures may have clinical relevance
      in substance use disorders.

PMID- 18331371
TI  - Effects of bupropion, alone or coadministered with nicotine, on social behavior
      in mice.
AB  - Bupropion, administered alone or combined with nicotine, is presently used to
      treat nicotine dependence. Despite experimental evidence of the complex
      behavioral actions of this drug, there have been little data reported about its
      effects on social behavior. Our main aim was to investigate the effects of acute
      administration of bupropion, alone or plus nicotine, on social interaction in
      mice. OF1 group-housed male mice were confronted in a neutral cage with an
      anosmic opponent during a 10 minutes encounter. Time allocated to body care and
      digging was reduced by administration of bupropion (40 mg/kg) both when
      administered alone and with nicotine (1 and 0.5 mg/kg). The lowest dose of
      bupropion (10 mg/kg) also reduced digging when combined with 1 mg/kg of nicotine.
      Time spent on non-social exploration and exploration from a distance was
      significantly higher in mice treated with bupropion (40 mg/kg) alone or combined
      with nicotine (1 and 0.5 mg/kg). The lowest dose of bupropion (10 mg/kg)
      increased non-social exploration when combined with 0.5 mg/kg of nicotine and
      exploration from a distance when combined with 1 mg/kg of nicotine.
      Ethopharmacological assessment of the behavior of groups of mice treated with
      different combinations of the two drugs indicates that nicotine can potentiate
      some of the behavioral effects of low doses of bupropion. Results also indicate
      that bupropion, either alone or combined with nicotine, has no significant
      effects on social investigation, suggesting that this drug does not induce a
      clear anxiolytic profile in OF1 mice.

PMID- 18331372
TI  - Smoking status moderates the association of the dopamine D4 receptor (DRD4) gene
      VNTR polymorphism with selective processing of smoking-related cues.
AB  - Recently, a variable number of tandem repeats (VNTR) polymorphism in the dopamine
      D4 receptor (DRD4) gene has been reported to be associated with greater craving
      and more attention to smoking cues, following a cue-elicited craving procedure.
      We investigated whether the DRD4 VNTR 7-repeat polymorphism is associated with
      selective processing of smoking-related stimuli, using a modified Stroop task,
      and whether smoking status moderates this association. Thirty-one current smokers
      and 17 ex-smokers attended a single testing session and completed the modified
      Stroop task. The experimental design included two between-subjects factors of
      smoking status (current smoker, ex-smoker) and DRD4 genotype (short, long). The
      DRD4 VNTR polymorphism was associated with selective processing of smoking
      related stimuli in ex-smokers but not in current smokers. Our data, therefore,
      provide partial support for our primary hypothesis and extend on previous work
      which suggests a role for variation at the DRD4 locus in modulating reactivity to
      drug-related cues.

PMID- 18331373
TI  - Disposition of Delta tetrahydrocannabinol in CF1 mice deficient in mdr1a P
      glycoprotein.
AB  - P-glycoprotein (P-gp) plays a major role in drug efflux. All the transported
      substrates are more or less hydrophobic and amphiphatic in nature. Being
      lipophilic, Delta(9) tetrahydrocannabinol (THC), the main cannabis component,
      could be a potential P-gp substrate. The aim of this project was to determine the
      contribution of the mdr1a gene product to THC disposition. Therefore, oral THC
      and digoxin (substrate test for P-gp) pharmacokinetics have been investigated in
      the intestinal epithelium and in the brain capillary endothelium of CF1 mdr1a-/-
      mice (mice naturally deficient in P-gp). These pharmacokinetics were compared to
      THC and digoxin oral pharmacokinetics in wild type mice mdr1a+/+ (not P-gp
      deficient). The application of Bailer's method showed that THC total exposure
      measured by the area under the plasma concentration time curve was 2.17-fold
      higher in CF1 mice naturally deficient in P-gp than in wild type mice after oral
      administration of 25 mg/kg of THC, and 2.4-fold higher after oral administration
      of 33 microg/kg of digoxin. As a consequence, the oral bioavailability of THC and
      digoxin was higher in naturally P-gp-deficient mice. We concluded that P-gp
      limits THC oral uptake and mediates direct drug excretion from the systemic
      circulation into the intestinal lumen.

PMID- 18331374
TI  - Pre-operative carbohydrate loading may be used in type 2 diabetes patients.
AB  - BACKGROUND: Post-operative insulin resistance and hyperglycaemia are associated
      with an impaired outcome after surgery. Pre-operative oral carbohydrate loading
      (CHO) reduces post-operative insulin resistance with a reduced risk of
      hyperglycaemia during post-operative nutrition. Insulin-resistant diabetic
      patients have not been given CHO because the effects on pre-operative glycaemia
      and gastric emptying are unknown. METHODS: Twenty-five patients (45-73 years)
      with type 2 diabetes [glycated haemoglobin (HbA1c) 6.2 +/- 0.2%, mean +/- SEM]
      and 10 healthy control subjects (45-72 years) were studied. A carbohydrate-rich
      drink (400 ml, 12.5%) was given with paracetamol 1.5 g for determination of
      gastric emptying. RESULTS: Peak glucose was higher in diabetic patients than in
      healthy subjects (13.4 +/- 0.5 vs. 7.6 +/- 0.5 mM; P<0.01) and occurred later
      after intake (60 vs. 30 min; P<0.01). Glucose concentrations were back to
      baseline at 180 vs. 120 min in diabetic patients and healthy subjects,
      respectively (P<0.01). At 120 min, 10.9 +/- 0.7% and 13.3 +/- 1.2% of paracetamol
      remained in the stomach in diabetic patients and healthy, subjects respectively.
      Gastric half-emptying time (T50) occurred at 49.8 +/- 2.2 min in diabetics and at
      58.6 +/- 3.7 min in healthy subjects (P<0.05). Neither peak glucose, glucose at
      180 min, gastric T50, nor retention at 120 min differed between insulin (HbA1c
      6.8 +/- 0.7%)- and non-insulin-treated (HbA1c 5.6 +/- 0.4%) patients.
      CONCLUSIONS: Type 2 diabetic patients showed no signs of delayed gastric
      emptying, suggesting that a carbohydrate-rich drink may be safely administrated
      180 min before anaesthesia without risk of hyperglycaemia or aspiration pre
      operatively.

PMID- 18331375
TI  - Clinical pharmacology of methadone for pain.
AB  - BACKGROUND: This topical review addresses methadone's pharmacology, its
      application in malignant and non-malignant pain conditions, practical issues
      related to methadone for the treatment of pain and its influence on QTc time.
      METHODS: Relevant papers were identified in PubMed and EMBASE. RESULTS: Methadone
      is advocated by experts as a second line opioid when first line opioids fail to
      provide a satisfactory balance between pain control and side effects (opioid
      switching). Although randomized-controlled studies are lacking, current evidence
      suggests that switching to methadone in this situation reduces pain intensity.
      However, interindividual variability in its pharmacokinetics make its application
      challenging and metabolism by CYP 3A4 and 2B6 implies a substantial risk of drug
      drug interactions. Several ways of switching to methadone have been presented,
      with a gradual switch during 3 days or 'stop and go' as the dominating
      strategies. Episodes of torsade de pointes arrhythmia during methadone treatment
      have been reported in patients with other risk factors for arrhythmia, while
      small prospective studies have reported a small, lasting and stable increase in
      QTc time. The extensive use of methadone for opioid replacement in addicts has
      added additional patient barriers to its use for pain control. CONCLUSION: In
      spite of challenges related to the variable pharmacokinetics and concerns
      regarding increase in QTc time, current evidence indicates that opioid switching
      to methadone improves pain control in a substantial proportion of patients who
      are candidates for opioid switching. Measures must be instituted to secure that
      patients receiving methadone for pain are not considered opioid addicts.

PMID- 18331376
TI  - Conjoint developmental trajectories of young adult substance use.
AB  - BACKGROUND: Despite the prominence of comorbidity among substances and the recent
      attention focused on trajectory-based approaches to characterizing developmental
      change, little research in the substance use field has simultaneously considered
      both course and comorbidity. METHODS: Using nationally representative panel data
      from the Monitoring the Future Project (MTF; n = 32,087; 56% female; 82%
      Caucasian), we identified developmental courses of heavy drinking, smoking, and
      marijuana use using 4 waves of data spanning ages 18 to 26 in a multi-cohort
      young adult sample. Comorbidity was examined by cross-classifying group
      membership in substance use trajectories. Finally, the extent to which risk
      factors (sex, race, alcohol expectancies, delinquency, sensation seeking,
      depressive affect, religiosity, academic achievement, and parent education)
      accounted for combinations of comorbidity that occurred at a rate greater than
      chance was examined. RESULTS: For each substance, we identified 4 courses of
      substance use that were largely consistent with those found in the literature
      (chronic high use, late-onset use, developmentally limited use, and low-use),
      with a fifth moderate smoking group. Heavy drinking, smoking, and marijuana use
      were each highly associated, and distinct patterns of comorbidity were evident,
      with greatest agreement along the diagonal. All risk factors explained
      comorbidity to some degree, with delinquency, sensation seeking, alcohol
      expectancies, and religion in particular predicting combinations of comorbidity
      that were characterized by early onset and chronic high use. CONCLUSIONS: Cross
      substance trajectory concordance was high, with parallel changes in substance use
      over emerging adulthood. This suggests similar developmental timing of use,
      perhaps due to the experience of developmental transitions that have a common
      influence on use of different substances. Prediction of combinations of
      comorbidity characterized by early onset and persistently high use suggests that
      to some extent, individuals use multiple substances because of a common
      vulnerability to each, rather than directional relations among substances (e.g.,
      cross-tolerance, cueing).

PMID- 18331377
TI  - Association of ADH and ALDH genes with alcohol dependence in the Irish Affected
      Sib Pair Study of alcohol dependence (IASPSAD) sample.
AB  - BACKGROUND: The genes coding for ethanol metabolism enzymes [alcohol
      dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] have been widely studied
      for their influence on the risk to develop alcohol dependence (AD). However, the
      relation between polymorphisms of these metabolism genes and AD in Caucasian
      subjects has not been clearly established. The present study examined evidence
      for the association of alcohol metabolism genes with AD in the Irish Affected Sib
      Pair Study of alcohol dependence. METHODS: We conducted a case-control
      association study with 575 independent subjects who met Diagnostic and
      Statistical Manual of Mental Disorders, 4th Edition, AD diagnosis and 530
      controls. A total of 77 single nucleotide polymorphisms (SNPs) in the seven ADH
      (ADH1-7) and two ALDH genes (ALDH1A1 and ALDH2) were genotyped using the Illumina
      GoldenGate protocols. Several statistical procedures were implemented to control
      for false discoveries. RESULTS: All markers with minor allele frequency greater
      than 0.01 were in Hardy-Weinberg equilibrium. Numerous SNPs in ADH genes showed
      association with AD, including one marker in the coding region of ADH1C
      (rs1693482 in exon6, Ile271Gln). Haplotypic association was observed in the ADH5
      and ADH1C genes, and in a long haplotype block formed by the ADH1A and ADH1B
      loci. We detected two significant interactions between pairs of markers in intron
      6 of ADH6 and intron 12 of ALDH2 (p = 5 x 10(-5)), and 5' of both ADH4 and ADH1A
      (p = 2 x 10(-4)). CONCLUSION: We found evidence for the association of several
      ADH genes with AD in a sample of Western European origin. The significant
      interaction effects between markers in ADH and ALDH genes suggest possible
      epistatic roles between alcohol metabolic enzymes in the risk for AD.

PMID- 18331380
TI  - Genetic and environmental influences on the rate of progression to alcohol
      dependence in young women.
AB  - BACKGROUND: The development of alcohol dependence (AD) involves transitions
      through multiple stages of drinking behaviors and is shaped by both heritable and
      environmental influences. We attempted to capture this dynamic process by
      characterizing genetic and environmental contributions to the rate at which women
      progressed through 3 significant transitions along the pathway to AD: nonuse to
      initiation, initiation to onset of first alcohol-related problem, and first
      problem to onset of AD. METHODS: The sample consisted of 3,546 female twins from
      the Missouri Adolescent Female Twin Study. Participants ranged in age from 18 to
      29 years. Retrospective reports of alcohol use histories were collected by
      telephone diagnostic interview and transition times between drinking milestones
      were coded ordinally. Standard genetic analyses were conducted in Mx to derive a
      trivariate model that provided estimates of genetic and environmental influences
      that were common as well as specific to the 3 transition times. RESULTS:
      Heritable influences were found for rate of progression across all 3 transitions,
      accounting for 30 to 47% of the variance in transition times. Shared
      environmental contributions were evident only in rate of progression from nonuse
      to initiation (i.e., age at first drink). Heritable contributions to the rate of
      movement through successive drinking milestones were attributable to a common
      factor, whereas environmental influences were transition-specific. CONCLUSIONS:
      The current study is unique in its use of a genetically informative design to
      document the rate of movement between drinking milestones in a female sample and
      to examine genetic contributions to multiple transition times over the course of
      AD development. Results indicate that an earlier report of heritability for males
      in rate of progression from regular drinking to AD generalizes to women and to
      other alcohol stage transitions. Findings also suggest the need to consider stage
      specific environmental contributions to alcohol outcomes in developing
      interventions.

PMID- 18331381
TI  - Survival and recovery of apheresis platelets stored in a polyolefin container
      with high oxygen permeability.
AB  - BACKGROUND AND OBJECTIVES: Oxygen permeability is important in platelet storage
      media. We compared a new polyolefin container with enhanced oxygen permeability
      (PO-80; Kawasumi, Tokyo, Japan) to a widely used alternative (PL2410; Baxter
      Healthcare, Deerfield, IL, USA). MATERIALS AND METHODS: In vitro characteristics
      of paired platelet concentrates (PCs; mean 4.2 x 10(11)/250 ml plasma/bag) stored
      in PO-80 or PL2410 were assessed through 9 days of storage. In vivo recovery and
      survival of 7-day-old autologous PCs were assessed according to the Murphy
      method. RESULTS: Laboratory assessment of platelet quality favoured PO-80 during
      9 days of storage with statistically significant differences in glucose
      consumption (2.75 vs. 4.93 mmol/10(12)/24 h in the interval 120-168 h), lactate
      generation (4.37 vs. 8.11 mmol/10(12)/24 h in the interval 120-168 h), pressure
      of oxygen (pO(2)) (59.3 vs. 38.1 mmHg at day 1), and HCO(3)(-) (14.7 vs. 13.4
      mmol/l at day 1). Statistically significant differences were not seen in
      aggregation, hypotonic shock response or pH. In vivo assessment of autologous
      platelets stored 7 days in the PO-80 container revealed that recovery was 82.1%
      and survival was 81.0% of fresh control. Seven-day stored PCs in PO-80 were shown
      in vivo to be non-inferior to fresh platelets, with upper confidence limits
      (UCL(95)) in recovery and survival of stored PCs below the maximum acceptable
      difference (MAD); 15.3% UCL(95) < 20.4% MAD and 2.1 days UCL(95) < 2.1 days MAD.
      CONCLUSIONS: The in vitro characteristics of PCs stored in a highly oxygen
      permeable container were stable at least 7 days. The in vivo study supports the
      suitability of PO-80 for 7-day platelet storage.

PMID- 18331382
TI  - Protein trafficking inside Toxoplasma gondii.
AB  - The accurate targeting of proteins to their final destination is an essential
      process in all living cells. Apicomplexans are obligate intracellular protozoan
      parasites that possess a compartmental organization similar to that of free
      living eukaryotes but can be viewed as professional secretory cells.
      Establishment of parasitism involves the sequential secretion from highly
      specialized secretory organelles, including micronemes, rhoptries and dense
      granules. Additionally, apicomplexans harbor a tubular mitochondrion, a
      nonphotosynthetic plastid organelle termed the apicoplast, acidocalcisomes and an
      elaborated inner membrane complex composed of flattened membrane cisternae that
      are derived from the secretory pathway. Given the multitude of destinations both
      inside and outside the parasite, the endoplasmic reticulum/Golgi of the
      apicomplexans constitutes one of the most busy roads intersections in eukaryotic
      traffic.

PMID- 18331383
TI  - The lysophospholipid acyltransferase antagonist CI-976 inhibits a late step in
      COPII vesicle budding.
AB  - The mechanism of coat protein (COP)II vesicle fission from the endoplasmic
      reticulum (ER) remains unclear. Lysophospholipid acyltransferases (LPATs)
      catalyze the conversion of various lysophospholipids to phospholipids, a process
      that can promote spontaneous changes in membrane curvature. Here, we show that
      2,2-methyl-N-(2,4,6,-trimethoxyphenyl)dodecanamide (CI-976), a potent LPAT
      inhibitor, reversibly inhibited export from the ER in vivo and the formation of
      COPII vesicles in vitro. Moreover, CI-976 caused the rapid and reversible
      accumulation of cargo at ER exit sites (ERESs) containing the COPII coat
      components Sec23/24 and Sec13/31 and a marked enhancement of Sar1p-mediated
      tubule formation from ERESs, suggesting that CI-976 inhibits the fission of
      assembled COPII budding elements. These results identify a small molecule
      inhibitor of a very late step in COPII vesicle formation, consistent with fission
      inhibition, and demonstrate that this step is likely facilitated by an ER
      associated LPAT.

PMID- 18331384
TI  - Is HIV infection associated with an increased risk for cholera? Findings from a
      case-control study in Mozambique.
AB  - OBJECTIVE: As residents of sub-Saharan Africa are at high risk for HIV and
      cholera, it is biologically plausible that immune suppression caused by HIV
      infection predisposes to cholera. Our aim was to assess the potential association
      between both diseases. METHODS: We conducted a case-control study in Beira,
      Mozambique, a high-risk area for HIV and cholera. Between 1 January 2005 and 30
      June 2006, experienced counsellors invited 132 suspected cholera cases and 528
      age- and sex-matched controls to an HIV counselling and testing centre. RESULTS:
      Forty (30%) of the invited cases and 127 (24%) of the invited controls came for
      HIV testing. No significant differences in demographic and socio-economic
      baseline characteristics were detected between participants and non-participants.
      Twenty five of 167 (15%) individuals who underwent testing were found HIV
      positive. The probability of a positive HIV-test was highest in participants
      between 40 and 49 years; 6 of 14 (43%) tested HIV-positive. Nine of 40 (23%)
      cholera cases were found to be HIV-infected compared with 16 of 127 (13%)
      controls (adjusted odds ratio 2.6; 95% CI 0.9-7.5; P = 0.08). DISCUSSION: The
      findings suggest that in a cholera-endemic area, HIV infection is associated with
      an increased risk for cholera. More research in HIV endemic settings is needed to
      confirm the findings and to explore the effect of HIV-related immunosuppression
      on the transmission of cholera.

PMID- 18331385
TI  - C-reactive protein and procalcitonin in the evaluation of the efficacy of a
      pneumococcal conjugate vaccine in Gambian children.
AB  - OBJECTIVE: To determine the value of C-reactive protein (CRP) and procalcitonin
      in the evaluation of the efficacy of a pneumococcal conjugate vaccine in Gambian
      children. METHODS: The investigation was done as a substudy of a phase III
      pneumococcal conjugate vaccine trial. A pilot study (n = 120) to compare CRP and
      procalcitonin concentrations in children with pneumonia was undertaken, followed
      by a larger study of CRP concentrations (n = 1868) obtained from a subsample of
      children with clinical pneumonia seen during the trial. RESULTS: In the pilot
      study, CRP had a higher sensitivity and specificity for the detection of primary
      endpoint (radiographic) pneumonia than procalcitonin. In the subsequent study of
      1868 episodes of clinical pneumonia, CRP showed moderate sensitivity but poor
      positive predictive value in identifying primary endpoint pneumonia or
      pneumococcal bacteraemia. Addition of CRP thresholds of 40, 60 or 120 mg/l to the
      diagnosis of clinical pneumonia did not give higher estimates of vaccine efficacy
      or vaccine attributable reduction in incidence than primary endpoint pneumonia.
      CONCLUSION: A combination of a raised CRP concentration with a clinical diagnosis
      of pneumonia is a more specific endpoint than clinical pneumonia alone but less
      appropriate than primary endpoint pneumonia as a measure of the impact of a
      pneumococcal vaccine in a Gambian setting.

PMID- 18331386
TI  - Laboratory reference values for healthy adults from southern Tanzania.
AB  - OBJECTIVES: To define and discuss reference ranges for commonly determined
      laboratory parameters in healthy adults from southern Tanzania. METHODS: A
      population-based sample of adult volunteers from Mbeya, Tanzania, who were not
      HIV positive or showing signs and symptoms of other diseases, participated in
      this study. We enrolled 145 women and 156 men between 19 and 48 years of age to
      determine clinical chemistry (CC), haematology and lymphocyte immunophenotyping
      (LIP) parameters using standard laboratory methods. Medians and nonparametric 95%
      reference ranges for each parameter were determined and compared with reference
      ranges from the USA, Europe and from other African countries. RESULTS: Agreement
      with ranges from developed countries was poor: for CC values the average
      concordance was 80.9% and 86.7% with values from two developed countries.
      Haematology ranges from the USA classified 86.3% of values correctly, whereas
      ranges from three different sub-Saharan Africa (SSA) sites classified between
      82.5% and 94.5% of values correctly. The agreement of LIP reference ranges was
      87.5% with values determined in Germany but between 91.7% and 95.8% compared with
      values determined at other sites in SSA. CONCLUSION: Clinical reference ranges
      determined in developed countries are inadequate for use in SSA. Laboratories in
      this region should either define their own or use values determined under similar
      conditions. The ranges reported here are more appropriate for use in SSA than
      ranges determined in developed countries.

PMID- 18331387
TI  - Evaluating non-adherence to immunosuppressant medications in pediatric liver
      transplant recipients.
AB  - Non-adherence with recommended immunosuppressant medications is common post
      pediatric liver transplant and is the most important reason for organ rejection
      in long-term survivors. However, there is currently no validated, standard method
      to measure adherence, with a well-defined threshold, making it extremely
      difficult to evaluate interventions to improve adherence. Previous studies have
      suggested that the degree of fluctuation of medication blood levels over time can
      provide an idea about how regularly the medication is being taken. The present
      study, conducted at UCLA medical center, sought to identify a specific threshold
      value of the s.d. of individual tacrolimus blood levels in pediatric liver
      transplant recipients which would be associated with rejection episodes in these
      patients. A threshold of 3.0 has been identified in other studies, and was
      supported by the analysis of retrospective data from 96 subjects. However,
      further analysis found that a s.d. of 2.5 appeared to have a better fit with the
      data. These findings suggest the utility of monitoring the s.d. of routine
      tacrolimus blood levels in pediatric liver transplant recipients for detecting
      non-adherence to immunosuppressant medication prior to clinical rejection,
      allowing earlier interventions.

PMID- 18331388
TI  - Living donor liver transplantation for children in highly urgent life-threatening
      situations.

PMID- 18331389
TI  - Invasive aspergillosis and allogeneic hematopoietic stem cell transplantation in
      children: a 15-year experience.
AB  - Despite progress in diagnosis and treatment, invasive aspergillosis (IA) remains
      a principal cause of mortality due to infection after allogeneic hematopoietic
      stem cell transplantation (AHSCT). In order to clarify the course of IA among
      children receiving an AHSCT before the advent of new drugs such as voriconazole
      or caspofungin, we retrospectively reviewed the medical records of all proven and
      probable IA between January 1986 and December 2000. 1) Ten children developed IA
      after AHSCT, mostly long after transplantation. Overall incidence was 2.7%. Seven
      of those children experienced 1 or more complications after AHSCT and before IA.
      Mortality was 90% with a median survival of 23 days (2-90). 2) Five children
      underwent AHSCT after a previous episode of IA. All patients were treated with
      systemic antifungal therapy combined with surgery. Median time between IA and
      AHSCT was 110 days (73-370). Two children were diagnosed with IA relapse after
      transplantation. One child was cured while the other died of IA and AHSCT
      complications. AHSCT could be considered even in the setting of previous IA, but
      established strategies implementing newer less toxic antifungal agents as
      treatment or prophylaxis in high-risk patients are needed.

PMID- 18331390
TI  - In vitro inhibition of CYP3A4 metabolism and P-glycoprotein-mediated transport by
      trade herbal products.
AB  - Extracts of six commonly used commercially available herbal products, St. John's
      wort, common valerian, common sage, Ginkgo biloba, Echinacea purpurea and horse
      chestnut were investigated for their in vitro inhibitory potential of CYP3A4
      mediated metabolism and P-glycoprotein efflux transport activity. C-DNA
      baculovirus expressed CYP3A4 and Caco-2 cells were used. Ketoconazole and
      verapamil were applied as positive control inhibitors, respectively. A validated
      high-performance liquid chromatography methodology was used to quantify the
      formation of 6-OH-testosterone and scintillation counting was used to quantify
      the transport of (3)H-digoxin. All the investigated herbs inhibited CYP3A4
      activity. St. John's wort was the strongest inhibiting herb with an IC(50) value
      of 15.4 microg/ml, followed by common sage, Ginkgo biloba, common valerian, horse
      chestnut and Echinacea purpurea. All herbs also inhibited P-glycoprotein
      activity. Ginkgo biloba was the strongest inhibiting herb, inhibiting the net
      digoxin flux with an IC(50) value of 23.6 microg/ml, followed by St. John's wort,
      horse chestnut, common sage, common valerian and Echinacea purpurea. No
      correlation was found between the herbs inhibitory potentials towards CYP3A4 and
      P-glycoprotein activities. Ginkgo biloba, horse chestnut and common sage, besides
      St. John's wort, are suggested candidates for in vivo intestinal herb-drug
      pharmacokinetic interactions.

PMID- 18331391
TI  - Serum aluminium levels in glue-sniffer adolescent and in glue containers.
AB  - Glue sniffing is a serious medical problem among teenagers. Various chemical
      substances such as toluene and benzene containing glues have been reported to be
      toxic. It has been demonstrated that some toxic metals such as lead are elevated
      in the blood of solvent-addicted patients. Whereas aluminium is an element that
      has toxic effects on neurological, hematopoetic system and bone metabolism. We
      want to determine the serum levels of aluminium in glue-sniffer adolescents in
      comparison with healthy subjects. In addition, we compared aluminium levels of
      different commercial glue preparations (i.e. metal and plastic containers), to
      determine which type of container is better for less aluminium toxicity. We
      measured serum levels of aluminium in 37 glue-sniffer and 37 healthy subjects
      using atomic absorption spectrophotometry. The average duration of glue-sniffer
      was 3.8 +/- 0.8 years. We also measured aluminium levels of 10 commercial glue
      preparations that seven of them with metal and three with plastic containers. We
      found that serum levels of aluminium were 63.29 +/- 13.20 ng/ml and 36.7 +/- 8.60
      ng/ml in glue-sniffer and in control subjects, respectively (P < 0.001). The
      average aluminium level in the glues was 8.6 +/- 3.24 ng/g in the preparations
      with metal containers, whereas 3.03 +/- 0.76 ng/g with plastic containers (P <
      0.001). Therefore, to decrease the incidence of aluminium toxicity in glue
      sniffers, it may be a good step to market of glue preparations in plastic instead
      of metal containers.

PMID- 18331392
TI  - Evaluation of cytotoxic, genotoxic and CYP450 enzymatic competition effects of
      Tanzanian plant extracts traditionally used for treatment of fungal infections.
AB  - HIV-infected patients in sub-Saharan countries highly depend on traditional
      medicines for the treatment of opportunistic oral infections as candidiasis.
      Previous investigations on antifungal activity of medicinal plant extracts
      utilized by traditional healers in Tanzania have revealed 12 extracts with potent
      antifungal activity. Although the plants may be good candidates for new treatment
      opportunities, they can be toxic or genotoxic and could cause pharmacokinetic
      interactions when used concomitantly with antiretroviral agents. Therefore, we
      investigated the cytotoxicity, genotoxicity and cytochrome P450 interaction
      potential of these medicinal plants. Cytotoxicity was tested by Hoechst 33342,
      Alamar Blue, calcein-AM, glutathione depletion and O(2)-consumption assays and
      genotoxicity by a Vitotox assay. Competition of the 12 extracts on substrate
      metabolism by CYP3A4, 2C9, 2C19 and 2D6 was tested with high-throughput CYP
      inhibition screening. Pregnane X receptor (PXR) activation was tested using
      Chinese hamster ovary cell lines expressing human PXR. Herbal extracts inducing
      high human PXR activation were tested for enhanced CYP3A4 mRNA levels with
      quantitative polymerase chain reaction. Genotoxicity was found for Jatropha
      multifida, Sterculia africana and Spirostachys africana. All plant extracts
      showed high cytotoxic effects in almost all tests. Potent competition with
      CYP3A4, 2D6, 2C9 and 2C19 was found for 75% of the herbal extracts. Spirostachys
      africana did not affect CYP2D6 and for S. africana and Turraea holstii no effect
      on CYP2D6 and CYP3A4 (DBF) was found. Nine plant extracts showed significant
      activation of human PXR, but only Agaura salicifolia, Turraea holstii and S.
      africana significantly induced CYP3A4 mRNA levels. These results indicate the
      possibility of potential medicinal plant-antiretroviral interactions.

PMID- 18331393
TI  - PJ34, a poly adenosine diphosphate-ribose polymerase inhibitor, attenuates
      chromate-induced nephrotoxicity.
AB  - Potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with
      oxidative stress. In addition, the activation of the polyadenosine diphosphate
      ribose [poly(ADP-ribose)] polymerase-1 (PARP-1) plays a role in the
      pathophysiology of some diseases associated with oxidative stress. To clarify the
      potential role of PARP-1 in this experimental model, N-(6-oxo-5,6-dihydro
      phenanthridin-2-yl)-N,N-dimethyacetamide HCl (PJ34), a highly specific inhibitor
      of this enzyme, was used. Nephrotoxicity was induced in rats by a single sc
      injection of K(2)Cr(2)O(7); studies were performed 2 days later. PJ34 was given
      intraperitoneally (15 mg/kg) 1 hr before and 1, 5, 24, 26, 31 and 46 hr after
      K(2)Cr(2)O(7) injection. Nephrotoxicity was evaluated by histological analysis
      and by measuring blood urea nitrogen, serum creatinine, serum glutathione
      peroxidase activity and urinary excretion of N-acetyl-beta-D-glucosaminidase.
      PARP-1 activation was evaluated by the immunostaining of poly(ADP-ribose). In
      addition, the following markers of oxidative stress were evaluated: 3
      nitrotyrosine, 4-hydroxy-2-nonenal, malondialdehyde and protein carbonyl content.
      K(2)Cr(2)O(7) increased poly(ADP-ribose) content suggesting the PARP-1 activation
      in this model. PJ34 significantly ameliorated the K(2)Cr(2)O(7)-induced: (i)
      nephrotoxicity, (ii) poly(ADP-ribose) accumulation and (iii) oxidative stress. It
      is concluded that PARP-1 is activated and involved, at least in part, in
      K(2)Cr(2)O(7)-induced nephrotoxicity in rats.

PMID- 18331394
TI  - Glutathione S-transferase null and cholesteryl ester transfer protein TaqI B
      polymorphisms and lipid response to atorvastatin in Greek dyslipidaemic patients.

PMID- 18331395
TI  - Protective effect of a multiantigenic DNA vaccine against Toxoplasma gondii with
      co-delivery of IL-12 in mice.
AB  - In this study, we constructed a multiantigenic DNA vaccine, pSAG1-ROP2-SAG2 and
      examined its effect with co-delivery of a plasmid encoding IL-12 (pIL-12) as an
      adjuvant in BALB/c mice against Toxoplasma gondii. After a lethal challenge of T.
      gondii RH strain, survival of the mice immunized with this pSAG1-ROP2-SAG2
      vaccine was significantly prolonged in comparison to the control groups.
      Furthermore, the protection was significantly augmented by pIL-12 co-delivery. As
      demonstrated by lymphocyte proliferation assay, cytokine and antibody level
      determinations, the humoral and Th1-type cellular responses elicited by this
      multiantigenic DNA vaccine were significantly stronger than those elicited by
      double-antigenic, or single-antigenic DNA vaccines. Our data suggest that
      multiantigenic DNA vaccine with pIL-12 co-delivery is a very effective approach
      in the protection against T. gondii.

PMID- 18331396
TI  - The length of esterifying alcohol affects the aggregation properties of
      chlorosomal bacteriochlorophylls.
AB  - Chlorosomes, the main light-harvesting complexes of green photosynthetic
      bacteria, contain bacteriochlorophyll (BChl) molecules in the form of self
      assembling aggregates. To study the role of esterifying alcohols in BChl
      aggregation we have prepared a series of bacteriochlorophyllide c (BChlide c)
      derivatives differing in the length of the esterifying alcohol (C(1), C(4), C(8)
      and C(12)). Their aggregation behavior was studied both in polar (aqueous buffer)
      and nonpolar (hexane) environments and the esterifying alcohols were found to
      play an essential role. In aqueous buffer, hydrophobic interactions among
      esterifying alcohols drive BChlide c derivatives with longer chains into the
      formation of dimers, while this interaction is weak for BChlides with shorter
      esterifying alcohols and they remain mainly as monomers. All studied BChlide c
      derivatives form aggregates in hexane, but the process slows down with longer
      esterifying alcohols due to competing hydrophobic interactions with hexane
      molecules. In addition, the effect of the length of the solvent molecules (n
      alkanes) was explored for BChl c aggregation. With an increasing length of n
      alkane molecules, the hydrophobic interaction with the farnesyl chain becomes
      stronger, leading to a slower aggregation rate. The results show that the
      hydrophobic interaction is the driving force for the aggregation in an aqueous
      environment, while in nonpolar solvents it is the hydrophilic interaction.

PMID- 18331397
TI  - Oxygen dependence of two-photon activation of zinc and copper phthalocyanine
      tetrasulfonate in Jurkat cells.
AB  - Photodynamic therapy (PDT), the use of light-activated drugs, is a promising
      treatment of cancer as well as several nonmalignant conditions. However, the
      efficacy of one-photon (1-gamma) PDT is limited by hypoxia, which can prevent the
      production of the cytotoxic singlet oxygen ((1)O(2)) species, leading to tumor
      resistance to PDT. To solve this problem, we propose an irradiation protocol
      based on a simultaneous, two-photon (2-gamma) excitation of the photosensitizer
      (Ps). Excitation of the Ps triplet state leads to an upper excited triplet state
      T(n) with distinct photochemical properties, which could inflict biologic damage
      independent of the presence of molecular oxygen. To determine the potential of a
      2-gamma excitation process, Jurkat cells were incubated with zinc or copper
      phthalocyanine tetrasulfonate (ZnPcS(4) or CuPcS(4)). ZnPcS(4) is a potent
      (1)O(2) generator in 1-gamma PDT, while CuPcS(4) is inactive under these
      conditions. Jurkat cells incubated with either ZnPcS(4) or CuPcS(4) were exposed
      to a 670 nm continuous laser (1-gamma PDT), 532 nm pulsed-laser light (2-gamma
      PDT), or a combination of 532 and 670 nm (2-gamma PDT). The efficacy of ZnPcS(4)
      to photoinactivate the Jurkat cells decreased as the concentration of oxygen
      decreased for both the 1-gamma and 2-gamma protocols. In the case of CuPcS(4),
      cell phototoxicity was measured only following 2-gamma irradiation, and its
      efficacy also decreased at a lower oxygen concentration. Our results suggest that
      for CuPcS(4) the T(n) excited state can be populated after 2-gamma irradiation at
      532 nm or the combination of 532 and 670 nm light. Dependency of phototoxicity
      upon aerobic conditions for both 1-gamma and 2-gamma PDT suggests that reactive
      oxygen species play an important role in 1-gamma and 2-gamma PDT.

PMID- 18331398
TI  - Salamander blue-sensitive cones lost during metamorphosis.
AB  - The tiger salamander lives in shallow water with bright light in the aquatic
      phase, and in dim tunnels or caves in the terrestrial phase. In the aquatic
      phase, there are five types of photoreceptors--two types of rods and three types
      of cones. Our previous studies showed that the green rods and blue-sensitive
      cones contain the same visual pigment and have the same absorbance spectra;
      however, the green rods have a larger photon-catch area and thus have higher
      light sensitivity than the blue-sensitive cones. Here we show that after
      metamorphosis, the terrestrial salamander looses the blue-sensitive cones, while
      the density of the green rods increases. Moreover, the size of the green rod
      outer segments is increased in the terrestrial phase, compared to that in the
      aquatic phase. This switch from the blue-sensitive cones to the green rods may
      represent an adaptation to the dim light environment of the terrestrial phase.

PMID- 18331399
TI  - Melanosomal damage in normal human melanocytes induced by UVB and metal uptake--a
      basis for the pro-oxidant state of melanoma.
AB  - Melanins are ubiquitous catecholic pigments, formed in organelles called
      melanosomes within melanocytes, the function of which is to protect skin against
      harmful effects of UV radiation. Melanosomes within melanoma cells are
      characteristically abnormal, with fragmented melanin and disrupted membranes. We
      hypothesize that the disruption of melanosomal melanin might be an early event in
      the etiology and progression of melanoma, leading to increased oxidative stress
      and mutation. In this report, we examine the effect of a combination of UV
      treatment and metal ion exposure on melanosomes within melanocytes, as well as
      their ability to act as pro-oxidants in ex situ experiments, and assay the
      effects of this treatment on viability and cell cycle progression. UVB exposure
      causes morphologic changes of the cells and bleaching of melanosomes in normal
      melanocytes, both significantly enhanced in Cu(II) and Cd(II)-treated cells, as
      observed by microscopy. The promoted bleaching by Cu(II) is due to its ability to
      redox cycle under oxidative conditions, generating reactive oxygen species;
      verified by the observed enhancement of hydroxyl radical generation when isolated
      melanosomes were treated with both Cu(II) ions and UVB, as assayed by DNA
      clipping. Single-dose UVB/Cu treatment does not greatly affect cell viability or
      cell cycle progression in heavily pigmented cells, but did so in an amelanotic
      early stage melanoma cell line.

PMID- 18331400
TI  - Quantum mechanical/molecular mechanical studies on spectral tuning mechanisms of
      visual pigments and other photoactive proteins.
AB  - The protein environments surrounding the retinal tune electronic absorption
      maximum from 350 to 630 nm. Hybrid quantum mechanical/molecular mechanical
      (QM/MM) methods can be used in calculating excitation energies of retinal in its
      native protein environments and in studying the molecular basis of spectral
      tuning. We hereby review recent QM/MM results on the phototransduction of bovine
      rhodopsin, bacteriorhodopsin, sensory rhodopsin II, nonretinal photoactive yellow
      protein and their mutants.

PMID- 18331401
TI  - Differentiation of the local structure around tryptophan 51 and 64 in recombinant
      human erythropoietin by tryptophan phosphorescence.
AB  - Recombinant human erythropoietin is a 4-helix bundle, glycosylated cytokine
      containing three tryptophan residues at positions 51, 64 and 88 whose
      phosphorescence emission may represent a sensitive probe of the structure at
      multiple sites near or at the protein surface. This report characterizes the
      phosphorescence properties (spectral energy, thermal spectral relaxation and
      phosphorescence lifetime), from low temperature glasses to ambient temperature,
      of the native protein plus that of three single point mutation analogs where each
      Trp was replaced by Phe. The structural information inferred from the
      phosphorescence parameters was essentially in good agreement with the structure
      of the Escherichia coli-produced nonglycosylated protein determined by nuclear
      magnetic resonance (Cheetham et al., Nat Struct Biol [1998] 5:861). The results
      showed that the fluorescence and phosphorescence spectra of the native protein
      were entirely due to independent contributions of Trp51 and Trp64 and that Trp88
      was quenched under all conditions. The phosphorescence emissions of Trp51 and
      Trp64 were differentiated by their unique spectra at 77 K with Trp64 exhibiting
      an unusually blueshifted spectrum likely due to the attractive interaction of
      Arg110 and Lys116 with the ground state dipole of Trp64. In the native protein
      the room temperature phosphorescence lifetime of Trp64 was relatively short with
      a time of 1.62 ms whereas the lifetime of Trp51 was five-fold longer.
      Characterization of the single point mutation analogs showed that each lifetime
      was composed of multiple components revealing the presence of multiple stable
      conformations of the protein at these surface sites.

PMID- 18331402
TI  - Jasmonic acid influences mycorrhizal colonization in tomato plants by modifying
      the expression of genes involved in carbohydrate partitioning.
AB  - The role of jasmonic acid (JA) on mycorrhizal colonization by Glomus fasciculatum
      in tomato plants was examined using mutant plants overexpressing prosystemin (PS)
      or affected in the synthesis of JA (suppressor of prosystemin-mediated responses
      2, spr2). The degree of mycorrhizal colonization was determined by measuring
      frequency (F%) and intensity (M%) of colonization and arbuscule abundance (A%).
      Gene expression and biochemical analyses were also performed in roots to detect
      changes in carbon (C) partitioning. Colonization was similar in mycorrhizal PS
      and wild-type roots, except for a higher A% in the former. Conversely,
      colonization was severely reduced in roots of spr2 mutants. No association was
      found between levels of expression of genes coding for systemic wound responsive
      proteins (or SWRPs) and other defense-related proteins in roots and
      mycorrhization levels in these plants. On the other hand, the degree of
      mycorrhizal colonization correlated with changes in the transcriptional
      regulation of a number of genes involved in sucrose hydrolysis and transport,
      cell wall invertase activity and mycorrhizal-specific fatty acid content in
      roots. The results obtained suggest that one of the mechanisms by which JA might
      operate to modulate the mycorrhization process could be through its influence on
      the regulation of C partitioning in the plant. The significant colonization
      increase observed in mycorrhizal spr2 plants supplied with exogenous methyl
      jasmonate supports its role as a positive regulator of the symbiosis.

PMID- 18331403
TI  - Group 2 sigma factors in cyanobacteria.
AB  - Group 1 and group 2 sigma factors are sigma factors of bacterial RNA polymerase
      responsible for transcription from consensus-type promoters. Thus, these sigma
      factors form the framework for basic transcriptional regulation in bacteria.
      Cyanobacteria are known to have various group 2 sigma factors, typically more
      than 4, but only recently the particular function of each sigma factor is being
      elucidated. In response to environmental signals such as nutrients, light and
      temperature, cyanobacteria change their transcriptional profile first by
      activating specific transcription factors and subsequently by modifying the basic
      transcriptional machinery, which is often involved in the regulation of group 2
      sigma factors. In this article, we give an overview of the composition and
      evolution of group 2 sigma factors in cyanobacteria and summarize what was
      presently revealed regarding their function.

PMID- 18331404
TI  - The effect of potassium nutrition on pest and disease resistance in plants.
AB  - Providing a fast growing world population with sufficient food while preserving
      ecological and energy resources of our planet is one of the biggest challenges in
      this century. Optimized management of chemical fertilizers and pesticides will be
      essential for achieving sustainability of intensive farming and requires both
      empirical data from field trials and advanced fundamental understanding of the
      molecular processes controlling plant growth. Genes involved in plant responses
      to nutrient deficiency and pathogen/herbivore attack have been identified, but we
      are lacking information about the cross-talk between signalling pathways when
      plants are exposed to a combination of abiotic and biotic stress factors. The
      focus of this review is on the relationship between the potassium status of
      plants and their susceptibility to pathogens and herbivorous insects. We combine
      field evidence on potassium-disease interaction with existing knowledge on
      metabolic and physiological factors that could explain such interaction, and
      present new data on metabolite profiles and hormonal pathways from the model
      plant Arabidopsis thaliana. The latter provides evidence that facilitated entry
      and development of pathogens or insects in(to) potassium-deficient plants as a
      result of physical and metabolic changes is counteracted by an increased defence.
      A genetic approach should now be applied to establish a causal relationship
      between disease susceptibility on the one hand and individual enzymatic and
      signal components on the other. Once identified, these can be used to design
      agricultural strategies that support the nutritional status of the crops while
      exploiting their inherent potential for defence.

PMID- 18331405
TI  - Polyphenol oxidase can cross thylakoids by both the Tat and the Sec-dependent
      pathways: a putative role for two stromal processing sites.
AB  - Polyphenol oxidase (PPO; EC 1.10.3.2 or EC 1.14.18.1), a thylakoid-lumen protein
      encoded by a nuclear gene, plays a role in the defense of plants against both
      herbivores and pathogens. Although previously reported to be a Tat (twin-arginine
      dependent translocation) protein, the import of PPO by isolated chloroplasts was
      inhibited by azide, a diagnostic inhibitor of the Sec-dependent pathway. Import
      of PPO inhibited thylakoid translocation of a Tat protein and did not affect
      translocation of Sec-dependent proteins. In contrast, a pre-accumulated iPPO
      competed with Sec-dependent but not with Tat proteins. A previously reported
      second processing step in the stroma removes a twin-Arg that is part of a 'Sec
      avoidance' motif in the thylakoid targeting domain of PPO. When the second
      processing site was mutated, the import of the resulting precursor showed Sec
      dependent characteristics. The PPO transit peptide could drive thylakoid
      translocation of a Tat protein in the dark. Azide inhibited the secretion of a
      PPO intermediate that lacks a twin-Arg to the periplasm of Escherichia coli, but
      had no effect on the export of the intermediate containing the twin-Arg. PPO is
      synthesized in plants in response to wound and pathogen-related signals and it is
      possible that when the Tat pathway is unable to translocate adequate amounts of
      newly synthesized PPO, translocation is diverted to the Sec-dependent pathway by
      processing the intermediate at the second site and removing the twin-Arg.

PMID- 18331406
TI  - Potassium influences on yield and quality production for maize, wheat, soybean
      and cotton.
AB  - Potassium is one of the principle plant nutrients underpinning crop yield
      production and quality determination. While involved in many physiological
      processes, potassium's impact on water relations, photosynthesis, assimilate
      transport and enzyme activation can have direct consequences on crop
      productivity. Potassium deficiency can lead to a reduction in both the number of
      leaves produced and the size of individual leaves. Coupling this reduced amount
      of photosynthetic source material with a reduction in the photosynthetic rate per
      unit leaf area, and the result is an overall reduction in the amount of
      photosynthetic assimilates available for growth. The production of less
      photosynthetic assimilates and reduced assimilate transport out of the leaves to
      the developing fruit greatly contributes to the negative consequences that
      deficiencies of potassium have on yield and quality production. Goals aimed
      toward increasing crop productivity and improved quality dictate either increased
      potassium supply or more efficient use of potassium. Developing plants that more
      efficiently use potassium might be a worthwhile goal for geneticists.

PMID- 18331407
TI  - Relationship between cytoplasmic male sterility and SPL-like gene expression in
      stem mustard.
AB  - We studied how mitochondria-nuclear interactions may give rise to cytoplasmic
      male sterility (CMS) in stem mustard exhibiting abnormal microsporogenesis. In
      this system, expression of SPL-like, the counterpart of the Arabidopsis nuclear
      gene SPOROCYTELESS, is specifically lost in buds of CMS plants. When
      mitochondrial-specific inhibitors were applied to wild-type fertile stem mustard
      plants, expression of SPL-like was repressed to some extent. As a consequence,
      the shape and vigor of pollen grains were severely affected, whereas the
      fertility of pistils remained unaltered. Thereby, we suggest that a probable
      pathway responsible for CMS in stem mustard involves mitochondrial retrograde
      regulation, with SPL-like as a target nuclear gene for a mitochondrial signal.

PMID- 18331408
TI  - Attitudes to psychological groups in a paediatric and adolescent diabetes service
      -implications for service delivery.
AB  - OBJECTIVE: To explore the potential interest in psychology support groups in a
      paediatric and adolescent diabetes service. RESEARCH DESIGN AND METHODS: A short
      semi-structured interview using both open and closed questions to generate
      quantitative and qualitative data. Sixty-four parents were interviewed on the
      telephone by an assistant psychologist. RESULTS: The majority of parents (81%)
      reported an interest in participating in a psychology group if it was offered,
      but preferences varied between a child/young person group (33%), parents only
      (15%) or family groups (11%). Twenty-three percent said that they would prefer
      individual work rather than a group. Parents identified groups as an opportunity
      to acquire practical knowledge, exchange ideas in an informal setting, share a
      common reality with others and gain more confidence in managing diabetes together
      with their child. Reasons not to attend a group included parents being able to
      cope well at the moment, school demands, feeling uncomfortable speaking in front
      of a group and use of online support groups. CONCLUSION: The majority of parents
      identified psychological support as having a role for families living with
      diabetes. The audit highlighted that families have different ideas about how they
      would prefer this support to look and emphasized the need to consult with service
      users when designing psychological support for young people and families living
      with a chronic condition.

PMID- 18331409
TI  - Trends, associations and predictions of insulin resistance in prepubertal
      children (EarlyBird 29).
AB  - BACKGROUND: Rising obesity has been observed in all age groups. Anthropometric
      cut-points have been used to predict metabolic risk in children, although they
      are not based on known outcomes. AIM: We examined the trends, associations and
      predictions of metabolic health from anthropometry in prepubertal children.
      METHOD: Three hundred and seven healthy children were examined annually between 5
      and 8 yr. MEASURES: height, weight, body mass index (BMI), sum of skinfold
      thickness at five sites (SSF) and waist circumference (WC). OUTCOME MEASURES:
      homeostasis model assessment of insulin resistance (HOMA-IR), high-density
      lipoprotein cholesterol (HDL-C) and triglycerides (TG). RESULTS: Two hundred and
      thirty-one [131 boys (B) and 100 girls (G)] children had complete data sets at
      all four time points. (i) All measures of adiposity rose from 5 to 8 yr (BMI - B:
      +3.4%, G: +5.7%; WC - B: +10.4%, G: +11.8%; SSF - B: +23.3%, G: +30.7%, all p <
      0.001). HOMA-IR unexpectedly fell (B: -16.6%, p = 0.01; G: -32.5%, p < 0.001).
      This fall was significant between 5 and 6 yr in both genders (5-6 yr - B: -17.8%,
      p < 0.001; G: -20.0%, p = 0.002) and between 6 and 7 yr in girls only (6-7 yr -
      B: -10.8%, p = 0.12; G: -19.2%, p = 0.001). HDL-C rose (B: +17.8%, G: +17.1%,
      both p < 0.001) and TG fell (B: -4.8%, p = 0.16; G: -11.6%, p = 0.006). (ii)
      Correlations between insulin resistance (IR) and anthropometry were poor at 5 yr
      but strengthened by 8 yr (BMI - B: r = 0.20/0.38, G: r = 0.28/0.49; WC - B: r =
      0.25/0.40, G: r = 0.32/0.58; SSF - B: r = 0.11/0.36, G: r = 0.18/0.53). (iii) In
      girls, but not boys, adiposity at 5 yr predicted IR better at 8 yr (BMI - r(2 )=
      0.17; WC - r(2 )= 0.28; SSF - r(2 )= 0.17, all p < 0.001) than it did at 5 yr
      (BMI - r(2 )= 0.08, p < 0.01; WC - r(2 )= 0.10, p < 0.01; SSF - r(2 )= 0.03, p =
      0.07). CONCLUSIONS: Cross-sectional association cannot indicate direction of
      trend or predict the future. Predicting metabolic health from anthropometric
      measures in prepubertal children requires longitudinal data, tracking variables
      from childhood into adulthood. Until the data set reaches adulthood, it is
      probably not safe to make recommendations on which children to 'target' or
      whether early intervention would be of benefit.

PMID- 18331410
TI  - Autosomal inheritance of diabetes in two families characterized by obesity and a
      novel H241Q mutation in NEUROD1.
AB  - BACKGROUND: The aim of the study was to search for mutations in the NEUROD1 and
      IPF-1 genes in patients with clinical characteristics of maturity-onset diabetes
      of the young (MODY) but with no mutations in the HNF-4A (MODY1), GCK (MODY2) and
      TCF1 (MODY3) genes. METHODS: We studied 30 unrelated Czech probands with a
      clinical diagnosis of MODY (median age at testing, 18 yr; median age at the
      recognition of hyperglycaemia, 16 yr). The promoter, exons and exon/intron
      boundaries of the NEUROD1 and IPF-1 genes were examined by polymerase chain
      reaction-denaturing high performance liquid chromatography and direct sequencing.
      RESULTS: While no mutations were found in the IPF-1 gene, a novel H241Q
      substitution of NEUROD1 gene was identified in two unrelated families. In the
      first proband, the H241Q mutation led to early diagnosed (20 yr) hyperglycaemia
      followed by development of diabetic microvascular complications by the age of 32
      yr. The second proband suffered from slowly progressing hyperglycaemia detected
      at the age of 30 yr. Affected members of both families were obese. The overall
      prevalence of the variant among the general population was 4 of 13 568
      chromosomes. CONCLUSIONS: We report a novel disease-associated variant in NEUROD1
      identified among a set of MODYX families. The variant seems to precipitate type-2
      like diabetes in excessively obese individuals.

PMID- 18331411
TI  - Perinatal risk factors for early childhood onset type 1 diabetes in Austria - a
      population-based study (1989-2005).
AB  - BACKGROUND: To investigate the rapid increase in incidence of type 1 diabetes
      mellitus (T1DM) in children <5 yr in Austria. METHODS: Data of children born
      between 1989 and 2005 (n = 444) from the T1DM children incidence registry were
      linked with birth certificates (n = 1 407 829). RESULTS: Age of mother, level of
      education, birth weight, birth length, body mass index, and APGAR score at 10 min
      were not significant. Boys have about 25% higher risk than girls [hazard ratio =
      0.75, 95% confidence interval (CI): 0.62-0.91]. The risk of developing diabetes
      increases over time significantly (1989-1991 vs. 2001-2005, hazard ratio = 2.86,
      95% CI: 2.07-3.94). The linear effect of parity is borderline significant (p =
      0.045), with lower risks for second and later born siblings. Marital status is
      significant [hazard ratio = 0.73, 95% CI: 0.57-0.90)]. Native-born children
      exhibit twice as high risk as non-native children (hazard ratio = 0.51, 95% CI:
      0.37-0.71). Birth weight shows a positive but not significant effect on risk of
      T1DM. CONCLUSIONS: In this very young and rapidly increasing cohort of diabetic
      children <5 yr of age, no association with birth weight but with year of birth,
      gestational age, nationality and parity could be observed.

PMID- 18331412
TI  - Use of complementary and alternative medicine in children with type 1 diabetes
      mellitus - prevalence, patterns of use, and costs.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) is increasingly used in
      adults and children. Studies on CAM in diabetes have mainly focused on the adult
      population and its use among children with type 1 diabetes has not been well
      characterized. OBJECTIVES: This study determines prevalence, parental reasons and
      motivations, perceived effectiveness, costs, and communication of CAM use.
      Moreover, caregiver-related variables associated with the use of CAM were
      investigated. METHODS: A self-completed anonymous questionnaire was administered
      to parents of children with type 1 diabetes in four pediatric diabetes centers in
      Germany (Leipzig, Berlin, Stuttgart, and Bonn). RESULTS: Two hundred and twenty
      eight (65.9%) of 346 families completed the survey. Mean age of the diabetic
      patients was 11.9 +/- 3.8 yr. Forty two (18.4%) received one or more types of
      CAM, with the most common types being homeopathy (14.5%), vitamins and minerals
      (13.7%), modified diet (12.9%), aloe vera (7.3%), and cinnamon (5.6%). Users had
      a significantly higher family income and parental tertiary education (p < 0.05)
      and stated a significantly stronger interest in self-care (p < 0.01). Parents'
      motivations for using CAM were the hope for an improved well-being (92.1%), to
      try everything (77.8%), and assumption of fewer side effects (55.2%). Costs for
      the entire treatment varied between less than euro100 and up to euro5000, with
      mostly no reimbursement. CONCLUSIONS: Use of CAM in children with type 1 diabetes
      is less common than that documented for adults. Parents using CAM do not question
      the need for insulin. When using CAM, improved well-being and quality of life are
      important considerations where CAM can have a role.

PMID- 18331413
TI  - Improved glycemic control and lower frequency of severe hypoglycemia with insulin
      detemir; long-term experience in 105 children and adolescents with type 1
      diabetes.
AB  - OBJECTIVE: To assess the effect of the insulin analog detemir on glycemic control
      and severe hypoglycemia in children and adolescents with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: A retrospective chart analysis was performed in 105
      patients with type 1 diabetes after switching to insulin detemir between 2004 and
      2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn
      (NPH) insulin was replaced by insulin detemir if therapeutic goals were not
      reached and blood glucose levels were unpredictable or hardly controllable. In
      adolescents above 12 yr of age (n = 52), insulin detemir was started when
      changing to intensified insulin therapy. RESULTS: In children below 12 yr of age,
      hemoglobin A1c (HbA1c) at start was 8.3 +/- 0.8% and after 12 months of treatment
      with insulin detemir significantly lowered (7.6 +/- 0.6%, p < 0.001). In the age
      group above 12 yr of age at the start of the study, the improvement of HbA1c
      after 12 months of treatment was less pronounced (8.0 +/- 1.2 vs. 7.6 +/- 1.0%)
      but still significant (p < 0.01). The risk for severe hypoglycemia was
      significantly decreased compared with patients attending the outpatient clinic
      between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p =
      0.003). From the beginning to the end of the follow-up period, body mass index
      dropped significantly in children below 12 yr of age but no effect was observed
      in adolescents. CONCLUSIONS: Use of insulin detemir allows a safe nocturnal
      glycemic control in children and adolescents with type 1 diabetes and is
      associated with significantly improved HbA1c levels and fewer severe hypoglycemic
      events. This makes insulin detemir a most valuable new tool for the treatment of
      children and adolescents with type 1 diabetes.

PMID- 18331414
TI  - Progression to type 1 diabetes and autoantibody positivity in relation to HLA
      risk genotypes in children participating in the ABIS study.
AB  - BACKGROUND: Autoantibodies against beta-cell antigens together with human
      leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1
      diabetes (T1D). In this study, we have investigated the role of HLA-risk and 
      protective genotypes for development of beta-cell autoantibodies and progression
      to T1D in healthy children. METHODS: T1D-related HLA genotypes and autoantibodies
      against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies
      (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in
      unselected healthy children and children with T1D participating in the All Babies
      In Southeast Sweden (ABIS) study. RESULTS: GADA or IA-2A positivity at 5 yr of
      age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the
      age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants
      in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent
      autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA
      risk genotypes associated with T1D, whereas protective genotypes were seldom
      found in children with T1D. Children with permanent autoantibodies had more often
      risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No
      associations with HLA-risk or -protective genotypes were found for transient
      autoantibodies. CONCLUSIONS: The strong relation between HLA-risk alleles and T1D
      once again confirmed that HLA-risk genotypes play an important role for
      development of T1D. However, HLA genotypes seem not to explain induction of
      autoantibodies, especially transient autoantibodies, in the general population,
      emphasizing the role of environmental factors in the initiation of autoimmunity.
      It seems that HLA-risk genotypes are responsible for maturation of the permanent
      autoantibody response.

PMID- 18331415
TI  - Is there a second fragrance gene in rice?
AB  - Aromatic rice is highly prized by most rice consumers, and many countries
      cultivate traditional and improved aromatic varieties. 2-Acetyl-1-pyrroline (2AP)
      is the major aromatic compound in rice, and is believed to accumulate because of
      an eight-base-pair (8-bp) deletion in an allele at the fragrance locus. In this
      study, 2AP was quantified and the presence or absence of the fragrance allele
      (fgr) was determined in 464 samples of traditional varieties of rice from the
      T.T. Chang Genetic Resources Centre at the International Rice Research Institute.
      It was shown that a number of aromatic varieties, primarily from South and South
      East Asia, do not carry the 8-bp deletion, but 2AP was identified in both raw and
      cooked rice of these varieties. We suggest that the 8-bp deletion in fgr is not
      the only cause of aroma, and at least one other mutation drives the accumulation
      of 2AP. The amount of 2AP in most uniform fgr genotypes was not significantly
      different from that in aromatic nfgr genotypes, but several fgr genotypes,
      primarily from South Asia, reproducibly accumulated exceptionally large amounts
      of 2AP. We suggest that the mutation leading to 2AP in aromatic nfgr varieties
      possibly originated several times and, through either domestication or evolution,
      the fgr gene and other alleles leading to 2AP have combined in South Asia,
      leading to several highly aromatic traditional varieties. The identification of
      multiple mutations for 2AP will enable rice breeding programmes to select
      actively for multiple genetic sources of 2AP, leading to the development of
      highly aromatic and, consequently, high-quality varieties of rice.

PMID- 18331416
TI  - Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German
      schoolchildren.
AB  - There is growing evidence for an association between obesity and asthma, but
      little is known about the underlying mechanisms. We hypothesized that high plasma
      leptin and low plasma adiponectin concentrations might be related to asthma and
      allergies in children. Plasma leptin and adiponectin concentrations were measured
      in a cross-sectional study involving 462 children aged 10 years. Information on
      disease symptoms and diagnosis was collected by parental questioning.
      Multivariate linear and logistic regression models were used to assess the
      association between biomarkers and disease. High leptin levels were associated
      with increased lifetime prevalence of asthma [odds ratio (OR): 3.76; 95%
      confidence interval (CI): 1.42-9.92]. The relationship was particularly strong
      for non-atopic asthma (OR: 5.51; 95% CI: 1.99-17.51). No associations were
      observed between plasma leptin levels and hay fever, and rhinoconjunctivitis. Low
      adiponectin levels were associated with increased prevalence of both symptoms of
      atopic dermatitis (OR: 3.23; 95% CI: 1.28-7.76) and ever-diagnosed eczema (OR:
      2.35; 95% CI: 1.13-4.89). In girls and non-atopic children, stronger associations
      for both leptin and adiponectin levels with asthma than in boys and atopic
      children were observed. These results suggest that adipokines may contribute to
      increased asthma and allergy risk in obese subjects. Stronger associations among
      girls with non-atopic asthma may indicate diverse pathological mechanisms.

PMID- 18331417
TI  - Utility of impulse oscillometry in young children with asthma.
AB  - Impulse Oscillometry (IOS) was developed as a tool to measure lung function, and
      as it only requires passive cooperation, it has been successfully used in younger
      children. The aim of this study was to assess the utility of IOS compared to
      conventional spirometry for lung function measures in asthmatic Korean children
      aged 3 to 6 yrs. Total serum IgE levels, total eosinophil counts, and specific
      IgE levels were measured in 77 children with asthma and 55 control subjects. IOS
      and spirometry were performed in the children before and after bronchodilator
      administration. Asthmatic children significantly differed from control subjects
      in baseline resistance at 10 Hz and in their IOS-assessed bronchodilator
      responses through a Delta resistance at 5 Hz (mean, -27.4% vs. -13.1%; p =
      0.002), 10 Hz (mean, -20.4% vs. -11.5%; p = 0.012), 20 Hz (mean, -16.4% vs. 
      9.4%; p = 0.016), and 35 Hz (mean, -17.2% vs. -10.2%; p = 0.020). Conventional
      spirometry did not show statistically significant findings. Asthmatic children
      significantly differed from control subjects in IOS-assessed bronchodilator
      response through a Delta resistance at 5 Hz, both in atopic children and in non
      atopic children. For atopic children, atopic asthmatic children (n = 58) also
      significantly differed from atopic controls (n = 30) in baseline resistance at 10
      Hz, 20 Hz, 35 Hz and impedance and in IOS-assessed bronchodilator responses
      through a Delta resistance at 10 Hz and 35 Hz. There were some significant
      correlations between bronchodilator responses of spirometric parameters and IOS
      parameters. IOS is useful diagnostic tool in early asthma development and might
      be a helpful objective outcome measure of early interventions.

PMID- 18331418
TI  - The response of bovine beta-lactoglobulin-specific T-cell clones to single amino
      acid substitution of T-cell core epitope.
AB  - Cow's milk is one of the most common food allergens in the first year of life,
      with approximately 2.5% of infants experiencing an allergic reaction to it. Beta
      lactoglobulin (BLG) is one of the major allergens in cow's milk. Previously, we
      reported that four of six T-cell clones (TCC) which were established from cow's
      milk allergy patients recognized BLGp97-117 as the core sequence and also
      recognized BLG in association with the human leucocyte antigen (HLA)-DRB1*0405
      allele. Using two of these four TCCs, we evaluated the T-cell response to BLG
      peptides with single amino acid substitution or deletion and identified BLGp102
      112 as the minimum essential region in BLGp97-117. In the alanine-scan assay, the
      proliferative responses of TCCs to pE108A disappeared, and the proliferative
      responses of TCCs to pC106A decreased. In the analog peptide proliferation assay,
      pY102S had retained some T-cell response to the two TCCs. Collecting these
      results, we propose a motif for the interaction between the HLA-DRB1*0405 allele
      and antigen peptide, and suggest that BLGp105-108 are important residues to
      retain the TCR/BLG-peptide/HLA complex. pY102A and pY102S are partial agonists
      for the T-cell receptor. These peptides might be considered as candidate peptides
      for the modification of the T-cell response to BLG in cow's milk allergy.

PMID- 18331419
TI  - Growth effects of botulinum toxin type A injected into masseter muscle on a
      developing rat mandible.
AB  - OBJECTIVES: Botulinum toxin type A (BTX-A) reduces the muscular contractions by
      temporarily inhibiting the release of acetylcholine at the neuromuscular
      junction. The purpose of this study was to investigate the effects of the BTX-A
      injected into the masseter muscle of a developing rat mandible. MATERIALS AND
      METHODS: Four-week-old male (no. 80) Sprague-Dawley rats were divided into four
      groups: control group, saline group, BTX-A group and baseline control group. Rats
      of baseline group were sacrificed at 0 day to provide baseline values of the
      mandibular measurements. The masseter muscle of rats in the saline and the BTX-A
      group were administered with saline and BTX-A solutions respectively.
      Experimental animals were sacrificed after 4 weeks. RESULTS: The BTX-A group
      demonstrated smaller mandibular dimension compared with the other groups (P <
      0.05). Their condylar cartilages showed increased apoptosis at the proliferation
      stage of the reserve zone and masseter muscle fibers demonstrated atrophic
      changes. CONCLUSIONS: The result demonstrated BTX-A influence on inhibitory
      action of the developing mandible because of apoptosis at the proliferation stage
      of the reserve zone of the condylar cartilage in developing rat mandible.

PMID- 18331420
TI  - Indirect costs of obesity: a review of the current literature.
AB  - This study reviews the recent literature on the relationship between obesity and
      indirect (non-medical) costs. Medline and Web of Science searches were conducted
      to identify published studies from 1992 to present that report indirect costs by
      obesity status; 31 studies were included. The indirect costs were grouped into
      six categories: costs associated with absenteeism, disability, premature
      mortality, presenteeism, workers' compensation, and total indirect costs.
      Compared with non-obese workers, obese workers miss more workdays due to illness,
      injury, or disability. Costs of premature mortality vary substantially across
      countries. The results for presenteeism and workers' compensation were mixed.
      More research is needed to determine obesity's causal role in increasing indirect
      costs, especially for workers' compensation and presenteeism. Cohort and
      longitudinal study designs should be a priority.

PMID- 18331421
TI  - Pulmonary gas exchange in the morbidly obese.
AB  - The literature on pulmonary gas exchange at rest, during exercise, and with
      weight loss in the morbidly obese (body mass index or BMI > or = 40 kg m(-2)) is
      reviewed. Forty-one studies were found (768 subjects weighted mean = 40 years
      old, BMI = 48 kg m(-2)). The alveolar-to-arterial oxygen partial pressure
      difference (AaDO2) was large at rest in upright subjects at sea level (23, range
      5-38 mmHg) while the arterial pressure of oxygen (PaO2) was low (81, range 50-95
      mmHg). Arterial pressure of carbon dioxide (PaCO2) was normal. At peak exercise
      (162 W), gas exchange improves. Weight loss of 45 kg (BMI = -13 kg m(-2)) over 18
      months is associated with an improvement in PaO2 (by 10 mmHg, range 1-23 mmHg), a
      reduction in AaDO2 (by 8 mmHg, range -3 to -16 mmHg), and PaCO2 (by -3 mmHg,
      range 3 to -14 mmHg) at rest. Every 5-6 kg reduction in weight increases PaO2 by
      1 and reduces AaDO2 by 1 mmHg, respectively. Morbidly obese women have better gas
      exchange at rest compared with morbidly obese men which is likely due to lower
      waist-to-hip ratios in women than from differences in weight or BMI.

PMID- 18331423
TI  - Tracking of childhood overweight into adulthood: a systematic review of the
      literature.
AB  - Overweight and obesity in youth are important public health concerns and are of
      particular interest because of possible long-term associations with adult weight
      status and morbidity. The aim of this study was to systematically review the
      literature and update evidence concerning persistence of childhood overweight. A
      computerized bibliographical search--restricted to studies with a prospective or
      retrospective longitudinal design--was conducted. Two authors independently
      extracted data and assessed the methodological quality of the included studies in
      four dimensions (i) study population and participation rate; (ii) study
      attrition; (iii) data collection and (iv) data analysis. Conclusions were based
      on a rating system of three levels of evidence. A total of 25 publications were
      selected for inclusion in this review. According to a methodological quality
      assessment, 13 studies were considered to be of high quality. The majority of
      these high-quality studies were published after 2001, indicating that recently
      published data, in particular, provide us with reliable information. All included
      studies consistently report an increased risk of overweight and obese youth
      becoming overweight adults, suggesting that the likelihood of persistence of
      overweight into adulthood is moderate for overweight and obese youth. However,
      predictive values varied considerably. Limiting aspects with respect to
      generalizability and methodological issues are discussed.

PMID- 18331422
TI  - Obesity and central obesity as risk factors for incident dementia and its
      subtypes: a systematic review and meta-analysis.
AB  - While dementia affects 6-10% of persons 65 years or older, industrialized
      countries have witnessed an alarming rise in obesity. However, obesity's
      influence on dementia remains poorly understood. We conducted a systematic review
      and meta-analysis. PUBMED search (1995-2007) resulted in 10 relevant prospective
      cohort studies of older adults (40-80 years at baseline) with end points being
      dementia and predictors including adiposity measures, such as body mass index
      (BMI) and waist circumference (WC). There was a significant U-shaped association
      between BMI and dementia (P = 0.034), with dementia risk increased for obesity
      and underweight. Pooled odds ratios (OR) and 95% confidence intervals (CI) for
      underweight, overweight and obesity compared with normal weight in relation to
      incident dementia were: 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93,
      2.18) respectively. Pooled ORs and 95% CI for obesity and incident Alzheimer's
      disease (AD) and vascular dementia were 1.80 (1.00, 3.29) vs. 1.73 (0.47, 6.31)
      and were stronger in studies with long follow-up (>10 years) and young baseline
      age (<60 years). Weight gain and high WC or skin-fold thickness increased risks
      of dementia in all included studies. The meta-analysis shows a moderate
      association between obesity and the risks for dementia and AD. Future studies are
      needed to understand optimal weight and biological mechanisms.

PMID- 18331424
TI  - Systems biology or the biology of systems: routes to reducing hunger.

PMID- 18331425
TI  - Insect-damaged fossil leaves record food web response to ancient climate change
      and extinction.
AB  - Plants and herbivorous insects have dominated terrestrial ecosystems for over 300
      million years. Uniquely in the fossil record, foliage with well-preserved insect
      damage offers abundant and diverse information both about producers and about
      ecological and sometimes taxonomic groups of consumers. These data are ideally
      suited to investigate food web response to environmental perturbations, and they
      represent an invaluable deep-time complement to neoecological studies of global
      change. Correlations between feeding diversity and temperature, between herbivory
      and leaf traits that are modulated by climate, and between insect diversity and
      plant diversity can all be investigated in deep time. To illustrate, I emphasize
      recent work on the time interval from the latest Cretaceous through the middle
      Eocene (67-47 million years ago (Ma)), including two significant events that
      affected life: the end-Cretaceous mass extinction (65.5 Ma) and its ensuing
      recovery; and globally warming temperatures across the Paleocene-Eocene boundary
      (55.8 Ma). Climatic effects predicted from neoecology generally hold true in
      these deep-time settings. Rising temperature is associated with increased
      herbivory in multiple studies, a result with major predictive importance for
      current global warming. Diverse floras are usually associated with diverse insect
      damage; however, recovery from the end-Cretaceous extinction reveals uncorrelated
      plant and insect diversity as food webs rebuilt chaotically from a drastically
      simplified state. Calibration studies from living forests are needed to improve
      interpretation of the fossil data.

PMID- 18331426
TI  - Influencing the binding configuration of sucrose in the active sites of chicory
      fructan 1-exohydrolase and sugar beet fructan 6-exohydrolase.
AB  - The hydrolytic plant enzymes of family 32 of glycoside hydrolases (GH32),
      including acid cell wall type invertases (EC 3.2.1.26), fructan 1-exohydrolases
      (1-FEH; EC 3.2.1.153) and fructan 6-exohydrolases (6-FEH; EC 3.2.1.154), are very
      similar at the molecular and structural levels, but are clearly functionally
      different. The work presented here aims at understanding the evolution of enzyme
      specificity and functional diversity in this family by means of site-directed
      mutagenesis. It is demonstrated for the first time that invertase activity can be
      introduced in an S101L mutant of chicory (Cichorium intybus) 1-FEH IIa by
      influencing the orientation of Trp 82. At high sucrose and enzyme concentrations,
      a shift is proposed from a stable inhibitor configuration to an unstable
      substrate configuration. In the same way, invertase activity was introduced in
      Beta vulgaris 6-FEH by introducing an acidic amino acid in the vicinity of the
      acid-base catalyst (F233D mutant), creating a beta-fructofuranosidase type of
      enzyme with dual activity against sucrose and levan. As single amino acid
      substitutions can influence the donor substrate specificity of FEHs, it is
      predicted that plant invertases and FEHs may have diversified by introduction of
      a very limited number of mutations in the common ancestor.

PMID- 18331427
TI  - Ethylene production in plants during transformation suppresses vir gene
      expression in Agrobacterium tumefaciens.
AB  - Ethylene evolution from plants inhibits Agrobacterium-mediated genetic
      transformation, but the mechanism is little understood. In this study, the
      possible role of ethylene in Agrobacterium-mediated genetic transformation was
      clarified. It was tested whether or not plant ethylene sensitivity affected
      genetic transformation; the sensitivity might regulate bacterial growth during co
      cultivation and vir gene expression in Agrobacterium tumefaciens. For these
      experiments, melon (Cucumis melo) was used, in which ethylene sensitivity was
      controlled by chemicals, and Arabidopsis ethylene-insensitive mutants.
      Agrobacterium-mediated genetic transformation was inhibited in ethylene-sensing
      melon, whereas, in Arabidopsis ethylene-insensitive mutant, it was enhanced.
      However, the ethylene sensitivity did not affect bacterial growth. vir gene
      expression was inhibited by application of plant exudate from ethylene-sensitive
      plants. The inhibitory effect of the ethylene sensitivity on genetic
      transformation relieved the activation of vir gene expression in A. tumefaciens
      with vir gene inducer molecule (acetosyringone, AS) or A. tumefaciens mutant
      strain which has constitutive vir gene expression. These results indicate that
      ethylene evolution from a plant inoculated with A. tumefaciens inhibited vir gene
      expression in A. tumefaciens through the ethylene signal transduction in the
      plant, and, as a result, Agrobacterium-mediated genetic transformation was
      inhibited.

PMID- 18331428
TI  - Physiology-phenology interactions in a productive semi-arid pine forest.
AB  - This study explored possible advantages conferred by the phase shift between leaf
      phenology and photosynthesis seasonality in a semi-arid Pinus halepensis forest
      system, not seen in temperate sites. Leaf-scale measurements of gas exchange,
      nitrogen and phenology were used on daily, seasonal and annual time-scales. Peak
      photosynthesis was in late winter, when high soil moisture, mild temperatures and
      low leaf vapour pressure deficit (D(L)) allowed high rates associated with high
      water- and nitrogen-use efficiencies. Self-sustained new needle growth through
      the dry and hot summer maximized photosynthesis in the following wet season,
      without straining carbon storage. Low rates of water loss were associated with
      increasing sensitivity of stomatal conductance (g(s)) to soil moisture below a
      relative extractable water (REW) of 0.4, and decreased g(s )sensitivity to D(L)
      below REW of approx. 0.2. This response was captured by the modified Ball-Berry
      (Leuning) model. While most physiological parameters and responses measured were
      typical of temperate pines, the photosynthesis-phenological phasing contributed
      to high productivity under warm-dry conditions. This contrasts with reported
      effects of short-term periodical droughts and could lead to different predictions
      of the effect of warming and drying climate on pine forest productivity.

PMID- 18331429
TI  - Yield and spatial supply of bioenergy poplar and willow short-rotation coppice in
      the UK.
AB  - Limited information on likely supply and spatial yield of bioenergy crops exists
      for the UK. Here, productivities are reported of poplar (Populus spp.) and willow
      (Salix spp.) grown as short-rotation coppice (SRC), using data from a large 49
      site yield trial network. A partial least-squares regression technique was used
      to upscale actual field trial observations across England and Wales. Spatial
      productivity was then assessed under different land-use scenarios. Mean modelled
      yields ranged between 4.9 and 10.7 oven-dry tonnes (odt) ha(-1) yr(-1). Yields
      were generally higher in willow than in poplar, reflecting the susceptibility of
      older poplar genotypes to rust and their tendency for single stem dominance.
      Replacing 10% of arable land, 20% of improved grassland and 100% of set-aside
      grassland in England and Wales with the three most productive genotypes would
      yield 13 Modt of biomass annually (supplying 7% of UK electricity production or
      48% of UK combined heat and power (CHP) production). Results show existing SRC
      genotypes have the immediate potential to be an important component of a mixed
      portfolio of renewables and that, in future, as new and improved genotypes become
      available, higher yields could extend this potential further.

PMID- 18331430
TI  - Gall insects can avoid and alter indirect plant defenses.
AB  - Parasitic species can dramatically alter host traits. Some of these parasite
      induced changes can be considered adaptive manipulations that benefit the
      parasites. Gall-inducing insects are parasites well known for their ability to
      alter host-plant morphology and physiology, including the distribution of plant
      defensive compounds. Here it was investigated whether gall-inducing species alter
      indirect plant defenses, involving the release of volatile compounds that are
      attractive to foraging natural enemies. Using field and factorial laboratory
      experiments, volatile production by goldenrod (Solidago altissima) plants was
      examined in response to attack by two gall-inducing species, the tephritid fly
      Eurosta solidaginis and the gelechiid moth Gnorimoschema gallaesolidaginis, as
      well as the meadow spittlebug, Philaenus spumarius, and the generalist
      caterpillar Heliothis virescens. Heliothis virescens elicited strong indirect
      defensive responses from S. altissima, but the gall-inducing species and
      spittlebugs did not. More significantly, infestation by E. solidaginis appeared
      to suppress volatile responses to subsequent attack by the generalist
      caterpillar. The extensive control that E. solidaginis apparently exerts over
      host-plant defense responses may reduce the predation risk for the gall inducer
      and the subsequent herbivore, and could influence community-level dynamics,
      including the distribution of herbivorous insect species associated with S.
      altissima parasitized by E. solidaginis.

PMID- 18331431
TI  - Candidate genotypes associated with functional dyspepsia.
AB  - There is accumulating evidence of a genetic predisposition for developing a
      functional gastrointestinal (GI) disorder. Identification of the genetic factors
      may improve understanding of underlying pathophysiological mechanisms. We aimed
      to test the association of functional polymorphisms in genes involved in
      serotonergic signalling and G-protein-mediated signal transduction, both
      affecting gastroduodenal sensory and motor function, with functional dyspepsia
      (FD). FD patients, send to our tertiary referral centre, were studied (n = 112).
      Healthy controls (n = 336) free of GI symptoms were matched 1 : 3 for age and
      gender. Polymorphisms in genes encoding the serotonin receptor type three A
      subunit (HTR3A), the serotonin transporter (SERT) and the G-protein beta3 subunit
      (GNB3) were analysed. The FD patients displayed a higher prevalence of the T
      allele of the GNB3 C825T polymorphism compared to healthy controls (OR = 1.60,
      95% CI: 1.03-2.49, P = 0.038). No association between FD and the genotype of the
      insertion/deletion polymorphism in the promoter of SERT (SERT-P) or HTR3A C178T
      polymorphism was observed. Tertiary referral FD is associated with the 825T
      allele of the GNB3 gene. The increased signal transduction associated with this
      allele may contribute to the abnormalities in gastroduodenal sensory and motor
      function observed in FD.

PMID- 18331432
TI  - Safety and diagnostic yield of laparoscopically assisted full-thickness bowel
      biospy.
AB  - Advances in minimally invasive surgery have made laparoscopy and full-thickness
      bowel biopsy possible in the investigation of patients with suspected
      gastrointestinal neuromuscular disorders. The safety and diagnostic yield of this
      investigation have not been formally reported. A prospective study was undertaken
      of 124 patients with clinico-physiological diagnoses of chronic intestinal pseudo
      obstruction, enteric dysmotility and severe irritable bowel syndrome undergoing
      LFTB in three European teaching centres with expertise in the management of
      gastrointestinal neuromuscular disorders. Perioperative data were collected
      including complications. Diagnostic yield was expressed as proportion with well
      established specific neuromuscular abnormalities based on a protocol of routine
      and immunohistochemical techniques. The majority of patients underwent a
      laparoscopically assisted procedure with extracorporeal biopsy. Median operating
      time was 50 min, conversion rate 2% and length of stay 1 day. There was an 8%
      readmission rate for obstructive symptoms but minimal other morbidity and no
      mortality. Overall specific diagnostic yield was 81%, being high for jejunal
      biopsies (89%) but low for a small number of ileal and colonic biopsies.
      Laparoscopy and full-thickness biopsy of the bowel appears acceptable in terms of
      safety. It should be performed in a jejunal site to achieve a high diagnostic
      yield.

PMID- 18331433
TI  - Chronic hepatitis ameliorates anaemia in haemodialysis patients.
AB  - BACKGROUND: Study for influence of chronic hepatitis (CH) on anaemia in
      haemodialysis (HD) patients remains inconclusive. We aim to characterize the red
      cell status between CH and hepatitis-free groups among the HD population.
      METHODS: We retrospectively analysed 80 chronic HD patients from Taipei Medical
      University Hospital with monthly sampled biochemical study between December 2004
      and December 2005. Data classified according to the hepatitis-free, chronic
      hepatitis B and C groups were expressed as mean +/- standard deviation. Student's
      t-test and anova were used to determine the mean difference for continuous
      variables. RESULTS: Age, Kt/V, systolic or diastolic blood pressure, body mass
      index, total cholesterol and triglyceride were not different between CH and
      hepatitis-free groups. HD duration (P = 0.0002), aspartate (P < 0.0001), alanine
      aminotransferase (P < 0.0001), alkaline phosphatase (P = 0.04), haemoglobin (P =
      0.0066) and haematocrit (P = 0.002) were significantly more elevated in the CH
      group demanding less erythropoietin dose than in the hepatitis-free group.
      CONCLUSION: Our study demonstrated that lessened anaemia was observed in CH,
      which demanded less erythropoietin dose.

PMID- 18331434
TI  - The evaluation of immune responses to hepatitis B vaccination in diabetic and non
      diabetic haemodialysis patients and the use of tetanus toxoid.
AB  - AIM: The aim of this study was to investigate whether haemodialysis (HD) patients
      suffering from diabetes mellitus could be considered at risk for the development
      of the protective antibodies to hepatitis B (HB) vaccination and, to evaluate the
      effectiveness of tetanus toxoid (TT) administrated 2 days before HB vaccination.
      METHODS: Forty-nine HD patients were divided into two groups: group A (19
      diabetic patients) and group B (30 non-diabetic patients). A dose of 40 microg
      recombinant HB vaccine was injected intramuscularly to the patients at 0, 1, 2
      and 6 months. RESULTS: After the completion of the course, the patients in group
      A were found to have a lower protective antibody rates than the patients in group
      B (57.8% vs 70%) (P > 0.05). After the administration of additional booster doses
      during 12 months, the protective antibody to hepatitis B surface antigen (HBsAb)
      levels were detected in 78.9% and 96.6% of the patients in group A and group B,
      respectively (P > 0.05). The patients not having protective HBsAb levels were
      administered TT and HB vaccines, and after course, all of them have produced
      protective HBsAb levels. CONCLUSION: The present study showed that diabetic
      patients on HD may carry a greater risk of not seroconverting than non-diabetic
      ones for antibody response to HB vaccination. The use of TT 2 days before HB
      vaccination may be a useful and effective method of enhancing the immune response
      to HB vaccination, especially in the patients with diabetes mellitus on HD.

PMID- 18331435
TI  - Anaemia in patients with chronic kidney disease: management with epoetin beta in
      primary care setting in New Zealand.
AB  - AIM: Anaemia is a major complication of advancing chronic kidney disease (CKD)
      and is amenable to treatment with epoetin. In order to manage the large number of
      CKD patients, it is essential that much of the care take place in primary care
      practices. METHODS: We describe a programme to treat anaemia with epoetin beta
      (EPO), using a simple referral and management protocol, by general practitioners
      remotely supported by a nephrologist and nurse coordinator team. RESULTS: Data
      for 79 patients treated between May 2005 and May 2007 was analysed. Patients were
      treated with stepwise alterations of EPO dose, beginning with 4000 units/week,
      and were followed up for a mean of 11 months (range 3-25). The mean age was 73
      years and 91% were of Caucasian origin. Sixty-seven per cent had stage 4 CKD and
      27% were at stage 3. Mean haemoglobin increased from 92.9 (standard deviation
      (SD) 7.1) to 118.5 (SD 11.7) g/L (P < 0.01). More than 75% achieved Hb of 110 g/L
      or more by the fifth month of therapy. Mean starting dose of EPO was 58.8 (SD
      25.0) and increased to 79.9 (SD 55.6) units/kg/week (P < 0.01). Mean serum
      ferritin decreased (P = 0.05), but transferrin saturation was not significantly
      altered. Estimated glomerular filtration rate remained stable. There was non
      significant elevation of systolic and diastolic blood pressure during treatment.
      CONCLUSION: The study demonstrates that treatment of anaemia with EPO can be
      successfully accomplished in primary care setting by general practitioners
      without the need for many patients to attend a nephrology clinic.

PMID- 18331436
TI  - Omega-3 fatty acid supplementation and total homocysteine levels in end-stage
      renal disease patients.
AB  - AIM: Elevated total homocysteine (tHcy) levels are commonplace among end-stage
      renal disease (ESRD) patients increasing risk for poor cardiovascular outcomes.
      Specifically, when plasma levels become significantly elevated, tHcy levels
      appear to contribute to vascular damage and premature atherosclerosis. The
      purpose of this study was to examine the effect of an over-the-counter omega-3 (n
      3) fatty acid supplementation on tHcy levels in ESRD patients undergoing chronic
      haemodialysis. METHODS: The present study was conducted using a double-blind,
      permuted-randomized and placebo-controlled experimental protocol. ESRD patients
      were followed prospectively while supplementing n-3 or corn oil (n-6)
      prospectively for 6 months. PATIENTS: Sixty-nine patients were recruited that had
      previously demonstrated compliance with dialysis and medication. Following a 12 h
      fast, participants donated 12 mL of blood for analysis of tHcy at baseline and at
      6 months. RESULTS: The results of this study using regression models revealed no
      differences in age and gender regarding homocysteine levels at the post-test with
      P-values of 0.6818, 0.6709 and 0.3331 for each regression model. The study
      findings also revealed that daily administration of 6 g of n-3 fatty acids
      containing 160 mg of eicosapentaenic acid (0.96 g/day) and 100 mg of
      docosahexaenoic acid (0.6 g/day) had no effect on tHcy levels when compared with
      control. CONCLUSION: Potential reasons for this non-significant result may be
      found in a dose-response relationship, advancement of disease progression in our
      sample population, or potentially the lack of a significant relationship between
      fish oil and tHcy. Future studies should address whether a dose-response
      relationship between n-3 fatty acid supplementation and tHcy levels exists, and
      how stage of disease progression affects intervention success or failure.

PMID- 18331437
TI  - Pretreatment with granulocyte colony-stimulating factor attenuated renal
      ischaemia and reperfusion injury via activation of PI3/Akt signal pathway.
AB  - AIM: Granulocyte colony-stimulating factor (G-CSF) has been shown to exert
      protective effects in various tissues and experimental models of ischaemia
      induced injury. However, the mechanism of renoprotective action in
      ischaemia/reperfusion (I/R) renal injury of G-CSF was unknown. METHODS: Male
      C57BL/6J mice, subjected to renal ischaemia for 45 min, 48 h and 7 days
      reperfusion, were administered either saline, wortmannin, G-CSF, and G-CSF plus
      wortmannin 3 days prior to I/R. Saline-treated group served as the control. At 48
      h and 7 days of reperfusion, the mice were killed. RESULTS: Significantly, renal
      dysfunction and morphological injury were identified at 48 h and 7 days after
      I/R. Wortmannin pretreatment worsened the renal injury significantly. However, G
      CSF pretreatment significantly attenuated renal injury, reduced the terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive ratio of
      renal tubular epithelial cells and inflammation cytokine expression in the
      kidney. Moreover, G-CSF pretreatment inhibited the expression of Bax and
      increased the expression of bcl-2 and p-Akt in the kidney. Wortmannin blunted the
      beneficial effects of G-CSF. CONCLUSION: The cytoprotective action of G-CSF
      against I/R injury seems to be associated with its anti-apoptotic action mediated
      by upregulation of p-Akt signal pathway.

PMID- 18331438
TI  - Human renal cells from the thick ascending limb and early distal tubule:
      characterization of primary isolated and cultured cells by reverse transcription
      polymerase chain reaction.
AB  - AIM: Human renal tubular cells of well-defined nephron origin are an important
      basis in the research of various physiological and pathophysiological mechanisms
      in the kidney. Whereas an exceeding amount of data has been obtained on proximal
      tubular cells, only limited data of cells of the human thick ascending limb and
      the early distal tubule (TALDC) are available. METHODS: TALDC have been isolated
      immunomagnetically according to their specific antigen expression of Tamm
      Horsfall glycoprotein (THG). Cells were either directly processed for analysis or
      cultured under normal cell culture conditions. Differentiation of primary
      isolates and cultured cells was assessed by reverse transcription polymerase
      chain reaction using characteristic markers. As controls, we used RNA from whole
      human kidney and cultured HK-2 cells. Additional characterizations were made by
      morphological analysis and western blotting. RESULTS: Primary isolated TALDC
      express the characteristic markers epidermal growth factor receptor, Na-K-2Cl
      transporter 2, epithelial calcium canal, and THG but were negative for Pax-2,
      aquaporin-2 and -3. Cultured TALDC were positive for epidermal growth factor
      receptor and Na-K-2Cl transporter 2 but have lost their epithelial calcium canal
      and THG expression and started to express Pax-2. All probes were positive for the
      specific markers kidney-specific cadherin and cytokeratin-8. Furthermore,
      differentiation of cultured TALDC was shown by cell morphology and their
      characteristic protein expression pattern. CONCLUSION: Our results highlight the
      purity of primary isolates and the differentiation of cultured TALDC, and show
      that they can be used as an in vitro system studies of the human thick ascending
      limb of Henle's loop and early distal tubule.

PMID- 18331439
TI  - Extracellular signal-regulated kinase-dependent interstitial macrophage
      proliferation in the obstructed mouse kidney.
AB  - AIM: A number of growth factors have been shown to induce proliferation of renal
      cell types in animal models of kidney disease. In vitro studies suggest that many
      such growth factors induce renal cell proliferation through the extracellular
      signal-regulated kinase (ERK) pathway. The aim of this study was to determine the
      functional role of ERK signalling in cell proliferation in the obstructed kidney.
      METHODS: Unilateral ureteric obstruction was induced in C57BL/6J mice which then
      received an ERK inhibitor drug (U0126 100 mg/kg t.i.d.), vehicle (DMSO) or no
      treatment, starting at day 2 after unilateral ureteric obstruction surgery and
      continuing until animals were killed on day 5. Cell proliferation was assessed by
      uptake of bromodeoxyuridine (BrdU). RESULTS: In normal mice, phosphorylation
      (activation) of ERK (p-ERK) was restricted to collecting ducts. Western blotting
      identified a marked increase in p-ERK in the obstructed kidney in the no
      treatment and vehicle-treated groups. Immunostaining showed strong p-ERK staining
      in many tubules and in interstitial cells. U0126 treatment inhibited ERK
      phosphorylation as assessed by western blot and immunostaining. The number of
      BrdU+ cortical tubular cells was reduced by vehicle treatment but was not further
      changed by U0126 treatment. In contrast, interstitial cell proliferation in the
      obstructed kidney was unaltered by vehicle treatment, but this was significantly
      inhibited by U0126. This was associated with a reduction in interstitial
      macrophage accumulation, but no effect was seen upon interstitial accumulation of
      alpha-SMA+ myofibroblasts. Renal fibrosis, as assessed by collagen deposition,
      was unaffected by U0126 or vehicle treatment. CONCLUSION: These studies show that
      accumulation of interstitial macrophages in the obstructed kidney is, in part,
      dependent upon the ERK signalling pathway.

PMID- 18331440
TI  - Endothelial nitric oxide synthase polymorphisms are associated with hypertension
      and cardiovascular disease in renal transplantation.
AB  - AIM: Nitric oxide (NO), produced by the polymorphic endothelial nitric oxide
      synthase (NOS3), plays an important role in endothelial function. The aim was to
      determine the effect of NOS3 polymorphisms on hypertension and cardiovascular
      disease (CVD) in renal allograft recipients. METHODS: Three polymorphisms of NOS3
      were examined in 168 renal allograft recipients. A 27 base pair repeat sequence
      in intron 4 (NOS3 a/b), a single G-->T substitution in exon 7 at nucleotide 894
      and a T-786C substitution in the promoter region were studied. RESULTS:
      Significant differences in the frequencies of the 894T and -786C alleles between
      allograft recipients and controls (n = 141) were demonstrated (894T: 40.5% vs
      30.1%, P < 0.01; -786C: 45.2% vs 34.4%, P < 0.01). There was a significant excess
      of both the 894T and -786C alleles in hypertensive allograft recipients compared
      with normotensive allograft recipients and controls (894T: 41.7%, 35.7% and
      30.1%, respectively, P < 0.025; -786C: 47.4%, 37.1% and 34.4%, respectively, P <
      0.01), and in allograft recipients with CVD compared with those without CVD and
      controls (894T: 47.2%, 38.6% and 30.1%, respectively, P < 0.025; -786C: 54.2%,
      42.8% and 34.4%, respectively, P < 0.01). CONCLUSION: The 894T and -786C alleles
      of the NOS3 gene were significantly associated with both hypertension and CVD in
      renal allograft recipients.

PMID- 18331441
TI  - Angiotensin II receptor blocker inhibits tumour necrosis factor-alpha-induced
      cell damage in human renal proximal tubular epithelial cells.
AB  - AIM: We investigated the effect of angiotensin II (AII) type 1 (AT1) and
      angiotensin II type 2 (AT2) receptor blockers on tumour necrosis factor alpha
      (TNF-alpha)-induced cell damage in human renal proximal tubular epithelial cells
      (RPTEC). METHODS: The lactate dehydrogenase (LDH) and N-acetyl-beta
      glucosaminidase (NAG) release into the medium after TNF-alpha treatment in RPTEC
      were determined using modified commercial procedures. In addition, the levels of
      caspase 3/7 activity in RPTEC were measured after TNF-alpha treatment with
      AlphaTau1 or AT2 receptor blockers. Finally we investigated the change of p22phox
      protein levels after TNF-alpha with AlphaTau1 or AT2 receptor blockers in RPTEC.
      RESULTS: Tumour necrosis factor alpha (10(-8) mol/L) significantly increased LDH
      and NAG release into the medium from RPTEC. AlphaTau1 receptor blockers,
      olmesartan and valsartan (10(-9)-10(-6) mol/L) showed a significant reduction on
      TNF-alpha-induced LDH and NAG release in RPTEC. AT2 receptor blocker, PD123319
      (10(-7)-10(-5) mol/L) also decreased TNF-alpha-induced LDH and NAG release in
      RPTEC. Blockade of both AlphaTau1 and AT2 receptor indicated additional reduction
      on TNF-alpha-induced LDH and NAG release. TNF-alpha (10(-8) mol/L) treatment
      showed small but significant increases of caspase 3/7 activity in RPTEC, and AT1
      and AT2 receptor blockers (10(-8) mol/L) comparably decreased TNF-alpha-induced
      caspase 3/7 activity. Significant increases of p22phox protein levels were
      observed in TNF-alpha-treated group in RPTEC. However, only AlphaTau1 (10(-8)
      mol/L) but not AT2 (10(-5) mol/L) receptor blocker significantly decreased TNF
      alpha-induced p22phox protein levels. CONCLUSION: The present study demonstrates
      that TNF-alpha induces renal tubular cell damage in RPTEC and AT1/AT2 receptor
      blockers showed cytoprotective effects probably via at least partly different
      mechanism.

PMID- 18331442
TI  - In vitro effect of cyclosporine-A on angiotensins secretion by glomerular cells.
AB  - AIM: Cyclosporine-A (CyA) is used to control transplant rejections and to treat
      autoimmune diseases. We investigated the possibility that changes induced by CyA
      on endothelin 1 (ET), angiotensin I (AI) and angiotensin II (AII) concentrations
      recognize a common pathway through which different mechanisms operate. METHODS:
      We measured ET, AI and AII concentrations, before and after either ET or CyA
      addition to the incubation medium of glomeruli of pig kidneys, isolated in vitro.
      The measurements were carried out with or without selective (ET(A) and ET(B)) or
      unselective ET(A)-ET(B) receptor inhibitors. RESULTS: In the presence of CyA, AI
      and ET are positively correlated either when ET(B) receptors are blocked, or when
      both receptors are free, while this correlation becomes negative when ET(A)
      receptors alone are blocked. Adding ET to the medium, the correlations between AI
      and ET are negative when either ET(A), or ET(B) or both are blocked. The effects
      of CyA and ET are significant only during the first 2 h of incubation.
      CONCLUSION: Cyclosporine-A recruits angiotensins and ET through ET(A) receptors,
      a mechanism possibly responsible of glomerular damage. This stimulation is time
      dependent. Prevention of the renal damage from CyA should require selective ET(A)
      receptor blockade.

PMID- 18331443
TI  - Calcineurin inhibitors and post-transplant weight gain.
AB  - AIM: Excessive weight gain that leads to obesity is quite common after kidney
      transplantation. This is often attributed to immunosuppression. The aim of this
      retrospective study was to assess the effect of calcineurin inhibitors on post
      transplant weight gain. METHODS: A total of 99 patients were studied. The
      patients were divided into cyclosporine A (CyA) and tacrolimus (Tac) groups and
      were evaluated for weight changes and risk factors related to weight gain.
      RESULTS: The weights of patients in both groups significantly increased after the
      sixth month. The median weight gain at 12 months was 3.5 and 8.0 kg compared with
      pretransplant dry weight in the Tac and CyA groups, respectively. The increases
      in the CyA group were significant compared with those of the Tac group. The
      prevalences of obese and overweight patients in both groups did not differ during
      a 12-month follow-up. The frequencies of diabetes mellitus, hypertension and
      dyslipidemia were comparable in both groups. The decrease in systolic blood
      pressure (BP) of the Tac group was significant compared with the decrease in the
      CyA group at the 12th month. In the 12-month follow-up period, the increases in
      triglyceride, total- and low-density lipoprotein-cholesterol values of the CyA
      group were significantly higher than those of the Tac group. The weight change
      between 0 and 12 months was negatively correlated with pretransplant body mass
      index (BMI) and positively with cumulative corticosteroid doses, total
      cholesterol and BP changes. CONCLUSION: Only pretransplant BMI, creatinine
      clearance, CyA usage, being hypertensive and dyslipidemic were independent
      predictors of weight gain at the 12th month. Our results suggested that the type
      of immunosuppression may affect post-transplant weight gain.

PMID- 18331444
TI  - Assessment of the lightcycler PCR assay for diagnosis of invasive aspergillosis
      in paediatric patients with onco-haematological diseases.
AB  - A reliable diagnosis of invasive aspergillosis (IA) is hampered by the difficulty
      in obtaining suitable tissue samples. To evaluate the sensitivity, specificity,
      positive predictive value (PPV) and negative predictive value (NPV) of the
      LightCycler PCR for the diagnosis of IA, 536 blood samples were collected over a
      22-month period from 62 paediatric patients (median age 10 years, range 1-18)
      considered at risk of IA. The galactomannan antigen (GM) and fungal DNA were
      assessed on serial blood samples. IA was diagnosed in eight of 62 patients (13%):
      proven, five, probable, three. Sensitivity, specificity, PPV and NPV of
      LightCycler PCR varied according to the number of positive samples used to define
      positivity: 88%; 37%; 17% and 95% for single sample positivity; and 63%, 81%, 33%
      and 94% for serial sample positivity respectively. The concordance between
      positivity of LightCycler PCR assay and the diagnosis of IA was 79%. The single
      positivity of LightCycler PCR assay showed a good sensitivity for the diagnosis
      of IA in paediatric patients. The high NPV makes LightCycler PCR a promising tool
      in addition to GM testing to design a strategy of pre-emptive antifungal therapy,
      although further validation studies are needed.

PMID- 18331445
TI  - Synergistic action of starch and honey against Aspergillus niger in correlation
      with Diastase Number.
AB  - To evaluate the synergistic action of starch on the antifungal activity of honey,
      a comparative method of adding honey with and without starch to culture media was
      used. Aspergillus niger was used to determine the minimum inhibitory
      concentration (MIC) of five varieties of honey. In the second step, lower
      concentrations of honey than the MIC were incubated with a set of concentrations
      of starch and then added to media to determine the minimum synergistic inhibitory
      concentration (MSIC). The MIC for the five varieties of honey without starch
      against A. niger ranged between 46% and 50% (v/v). When starch was incubated with
      honey and then added to media, an MIC drop was noticed with each variety and it
      ranged between 6% and 19.5%. Negative correlation has been established between
      the MIC drop and the Diastase Number.

PMID- 18331446
TI  - Screening of Thai medicinal plants for anticandidal activity.
AB  - Medicinal plants are often used in the treatment of various ailments. In this
      study, 23 of Thai medicinal plants were screened for their anticandidal activity
      against six pathogenic Candida species: C. albicans, C. glabrata, C.
      guilliermondii, C. krusei, C. parapsilosis and C. tropicalis. The methanol
      extract of Hibiscus sabdariffa L. fruit, Trigonostemon reidioides (Kurz) Craib
      root, Usnea siamensis Vain whole plant, Boesenbergia rotunda (L.) Mansf. rhizome,
      and Albizia myriophylla Benth. stem showed anticandidal activity against one or
      more species of Candida. Among them, A. myriophylla Benth. showed broad
      anticandidal activity. The susceptibility tests of A. myriophylla Benth. extract,
      in terms of minimal inhibitory concentrations (MIC) and minimal fungicidal
      concentration (MFC), were performed by the broth microdilution techniques as
      described by the Clinical Laboratory Standard Institute. MICs of A. myriophylla
      Benth. extract to all Candida species was ranged 100-500 mug ml(-1). The killing
      activity of A. myriophylla Benth. extract was fast acting against all Candida
      tested; the reduction in the number of CFU ml(-1) was >3 log(10) units (99.9%) in
      2 h. This study indicates that A. myriophylla Benth. extract has considerable
      anticandidal activity, deserving further investigation for clinical applications
      for the treatment of candidiasis.

PMID- 18331447
TI  - Embolic aspergillus endophthalmitis in an immunocompetent patient from aortic
      root aspergillus endocarditis.
AB  - We report the first case of endogenous aspergillus endophthalmitis in an
      immunocompetent person with systemic aortic root aspergillus endocarditis.

PMID- 18331448
TI  - Central nervous system infections by members of the Pseudallescheria boydii
      species complex in healthy and immunocompromised hosts: epidemiology, clinical
      characteristics and outcome.
AB  - Infections caused by members of the Pseudallescheria boydii species complex are
      currently among the most common mould infections. These fungi show a particular
      tropism for the central nervous system (CNS). We reviewed all the available
      reports on CNS infections, focusing on the geographical distribution, infection
      routes, immunity status of infected individuals, type and location of infections,
      clinical manifestations, treatment and outcome. A total of 99 case reports were
      identified, with similar percentage of healthy and immunocompromised patients
      (44% vs. 56%; P = 0.26). Main clinical types were brain abscess (69%), co
      infection of brain tissue and/or spinal cord with meninges (10%) and meningitis
      (9%). The mortality rate was 74%, regardless of the patient's immune status, or
      the infection type and/or location. Cerebrospinal fluid culture was revealed as a
      not very important tool as the percentage of positive samples for P. boydii
      complex was not different from that of negative ones (67% vs. 33%; P = 0.10). In
      immunocompetent patients, CNS infection was preceded by near drowning or trauma.
      In these patients, the infection was characterised by localised involvement and a
      high fatality rate (76%). In contrast, CNS infection in immunocompromised
      patients was presented as rapidly progressive disseminated lesions at various
      degrees of evolution. Major risk factors for CNS infection were the aspiration of
      polluted water in near-drowning episodes in immunologically intact patients and
      medical immunosuppression in the remaining patient groups. As the therapeutic
      options were poor, the treatment was difficult in general and the prognosis was
      poor.

PMID- 18331449
TI  - The clinical and pharmacoeconomic analysis of invasive aspergillosis in adult
      patients with haematological diseases.
AB  - Invasive pulmonary aspergillosis (IPA) poses major management problems for
      clinicians caring for patients with haematological diseases. The clinical courses
      of patients with IPA who had been hospitalised in Hematology Unit, Bone Marrow
      Transplantation Unit and Infectious Diseases and Clinical Microbiology Unit
      between 1998 and 2005, the efficacy and adverse effects and costs of antifungal
      drugs (conventional amphotericin B deoxycholate, liposomal amphotericin B,
      amphotericin B lipid complex and caspofungin) used in the therapy of these
      patients were analysed in this study. Ninety-three patients with IPA were
      reviewed retrospectively. Mean age of the patients was 40.4 +/- 15.1 years (range
      14-70 years). Fifty-eight male patients and 35 female patients were included in
      the study. Manageable hypopotassemia, nausea/vomiting and headache were the most
      commonly observed side-effects during antifungal (AF) therapy. While it was not
      found to be statistically significant with regard to the mean time to resolution
      of fever (P = 0.8), it was found to be statistically significant with regard to
      radiological regression at 30th day, and mean duration of therapy between
      patients who were dead or alive (P < 0.05, P < 0.001). Total cost of AF therapy
      for 93 patients was found to be US$4 461 824 (minimum US$387-maximum US$279 023).
      Of this amount, US$4 272 845 represents the payment for AF drugs, US$188 979 the
      payment for other expenditures. Mean cost of therapy for a patient with IPA was
      found to be US$49 336. Although it seemed to be difficult, investigations should
      primarily focus on providing standardisation of parameters relating to the
      duration of AF therapy. Despite the less-than-optimal safety profile of CAB, it
      often remains to be the preferred first line option for the treatment of fungal
      infections because of its broad spectrum, activity and low acquisition cost.

PMID- 18331450
TI  - Bacillus subtilis GlnR contains an autoinhibitory C-terminal domain required for
      the interaction with glutamine synthetase.
AB  - The Bacillus subtilis GlnR transcription factor regulates gene expression in
      response to changes in nitrogen availability. Glutamine synthetase transmits the
      nitrogen regulatory signal to GlnR. The DNA-binding activity of GlnR is activated
      by a transient protein-protein interaction with feedback-inhibited glutamine
      synthetase that stabilizes GlnR-DNA complexes. This signal transduction mechanism
      was analysed by creating mutant GlnR proteins with partial or complete
      truncations of their C-terminal domains. The truncated GlnR proteins were found
      to constitutively repress gene expression in vivo. This constitutive repression
      did not require glutamine synthetase. Purified mutant GlnR proteins bound DNA in
      vitro more tightly than wild-type GlnR protein and this binding was not activated
      by feedback-inhibited glutamine synthetase. While full-length GlnR is monomeric,
      the truncated GlnR proteins contained significant levels of dimers. These results
      indicate that the C-terminal region of GlnR acts as an autoinhibitory domain that
      prevents GlnR dimerization and thus impedes DNA binding. The GlnR C-terminal
      domain is also required for the interaction between GlnR and feedback-inhibited
      glutamine synthetase. Compared with the full-length GlnR protein, the truncated
      GlnR proteins were defective in their interaction with feedback-inhibited
      glutamine synthetase in cross-linking experiments.

PMID- 18331451
TI  - Exosome function: from tumor immunology to pathogen biology.
AB  - Exosomes are the newest family member of 'bioactive vesicles' that function to
      promote intercellular communication. Exosomes are derived from the fusion of
      multivesicular bodies with the plasma membrane and extracellular release of the
      intraluminal vesicles. Recent studies have focused on the biogenesis and
      composition of exosomes as well as regulation of exosome release. Exosomes have
      been shown to be released by cells of hematopoietic and non-hematopoietic origin,
      yet their function remains enigmatic. Much of the prior work has focused on
      exosomes as a source of tumor antigens and in presentation of tumor antigens to T
      cells. However, new studies have shown that exosomes might also promote cell-to
      cell spread of infectious agents. Moreover, exosomes isolated from cells infected
      with various intracellular pathogens, including Mycobacterium tuberculosis and
      Toxoplasma gondii, have been shown to contain microbial components and can
      promote antigen presentation and macrophage activation, suggesting that exosomes
      may function in immune surveillance. In this review, we summarize our
      understanding of exosome biogenesis but focus primarily on new insights into
      exosome function. We also discuss their possible use as disease biomarkers and
      vaccine candidates.

PMID- 18331453
TI  - Fibrinogen gene variation and ischemic stroke.
AB  - BACKGROUND: Plasma fibrinogen level and fibrin clot structure are heritable
      traits that may be of importance in the pathogenesis of ischemic stroke.
      OBJECTIVES: To investigate associations between variation in the fibrinogen gamma
      (FGG), alpha (FGA) and beta (FGB) genes, fibrinogen level, and ischemic stroke.
      METHODS: The Sahlgrenska Academy Study on Ischemic Stroke comprises 600 cases and
      600 matched population controls. Stroke subtypes were defined according to TOAST
      criteria. Plasma fibrinogen level was measured by an automated clot-rate assay.
      Eight tagging single nucleotide polymorphisms (SNPs) were selected to capture
      genetic variation in the FGA, FGG, and FGB genes. RESULTS: Plasma fibrinogen was
      independently associated with overall ischemic stroke and all subtypes, both in
      the acute stage (P < 0.001) and at three-month follow-up (P < 0.05). SNPs
      belonged to two haplotype blocks, one containing the FGB gene and the other the
      FGG and FGA genes. FGB haplotypes were associated with fibrinogen level (P <
      0.01), but not with ischemic stroke. In contrast, FGG/FGA haplotypes showed
      independent association to ischemic stroke but not to fibrinogen level. In an
      additive model with the most common FGG/FGA haplotype (A1) as reference, the
      adjusted odds ratios of ischemic stroke were 1.4 [95% confidence interval (95%
      CI) 1.1-1.8], P < 0.01, 1.4 (95% CI 1.0-1.8), P < 0.05, and 1.5 (95% CI 1.0-2.1),
      P < 0.05 for the A2, A3, and A4 FGG/FGA haplotypes, respectively. CONCLUSION:
      FGG/FGA haplotypes show association to ischemic stroke. This association is
      independent of fibrinogen level, thus suggesting that the association between
      ischemic stroke and variation at the FGG/FGA genes is mediated by qualitative
      rather than quantitative effects on fibrin(ogen).

PMID- 18331452
TI  - A role for EHD4 in the regulation of early endosomal transport.
AB  - All four of the C-terminal Eps15 homology domain (EHD) proteins have been
      implicated in the regulation of endocytic trafficking. However, the high level of
      amino acid sequence identity among these proteins has made it challenging to
      elucidate the precise function of individual EHD proteins. We demonstrate here
      with specific peptide antibodies that endogenous EHD4 localizes to Rab5-, early
      embryonic antigen 1 (EEA1)- and Arf6-containing endosomes and colocalizes with
      internalized transferrin in the cell periphery. Knock-down of EHD4 expression by
      both small interfering RNA and short hairpin RNA leads to the generation of
      enlarged early endosomal structures that contain Rab5 and EEA1 as well as
      internalized transferrin or major histocompatibility complex class I molecules.
      In addition, cargo destined for degradation, such as internalized low-density
      lipoprotein, also accumulates in the enlarged early endosomes in EHD4-depleted
      cells. Moreover, we have demonstrated that these enlarged early endosomes are
      enriched in levels of the activated GTP-bound Rab5. Finally, we show that
      endogenous EHD4 and EHD1 interact in cells, suggesting coordinated involvement in
      the regulation of receptor transport along the early endosome to endocytic
      recycling compartment axis. The results presented herein provide evidence that
      EHD4 is involved in the control of trafficking at the early endosome and
      regulates exit of cargo toward both the recycling compartment and the late
      endocytic pathway.

PMID- 18331454
TI  - Lower factor XII activity is a risk marker rather than a risk factor for
      cardiovascular disease: a rebuttal.

PMID- 18331455
TI  - Myocardial infarction and cerebrovascular accident following non-cardiac surgery:
      differences in postoperative temporal distribution and risk factors.
AB  - BACKGROUND: Myocardial infarction and stroke after non-cardiac surgery are two
      ominous cardiovascular complications believed to share similar pathophysiological
      processes. However, the differences in the temporal distribution between them
      have not been adequately investigated in a large cohort of patients. METHODS AND
      RESULTS: The preoperative clinical features and daily occurrence of myocardial
      infarction and stroke were routinely recorded in 36 634 consecutive patients
      following elective non-cardiac, non-carotid surgery. The preoperative
      characteristics and postoperative daily distribution of postoperative myocardial
      infarction and stroke were compared using exponential and linear regressions
      models. Myocardial infarction and stroke occurred in 122 (0.33%) and 126 (0.34%)
      patients, respectively, during the first 30 days after surgery. More patients
      with myocardial infarction had diabetes mellitus and cardiac disease (P = 0.041
      and <0.0001, respectively) whereas more patients with stroke were older and
      female (P = 0.003 and 0.038, respectively). The peak incidence of myocardial
      infarction was on the day of surgery (43%) and declined exponentially thereafter
      (F = 725.4, P < 0.0001). However, postoperative stroke best fitted a linear
      regression with almost even daily distribution (F = 15.9, P = 0.0004). The median
      time to myocardial infarction was one day [95% confidence interval (95% CI) = 0-2
      days] compared with nine days (95% CI = 7-11 days) for stroke. CONCLUSIONS: The
      peak incidence of postoperative myocardial infarction is early after non-cardiac
      surgery and declines exponentially thereafter, as opposed to stroke, which occurs
      at a constant rate during the postoperative period. Myocardial infarction and
      cerebrovascular accident following non-cardiac surgery differ in their
      preoperative risk factors, and in the postoperative time-line of their
      occurrence.

PMID- 18331456
TI  - Empty sites can promote altruistic behavior.
AB  - Spatial structure has been shown to promote altruistic behavior, however, it also
      increases the intensity of competition among relatives. Our purpose here is to
      develop a model in which this competition is minimized, more precisely a local
      increase in fecundity has a minimal competitive effect on the fitness of nearby
      individuals. We work with an island model in which sites are allowed to be empty,
      choosing our demographic rules so that in patches with higher fecundity, empty
      sites are filled at a higher rate. We also allow dispersal rates to evolve in
      response to the proportion of empty sites in the patch. Patches with different
      numbers of empty sites differ in frequency, in within-patch consanguinity, and in
      reproductive value. Using an inclusive fitness argument, we show that our model
      does promote altruism; indeed Hamilton's Rule is shown to hold. The only negative
      effect on an actor of a gift of fecundity to a patchmate turns out to be a slight
      decrease in reproductive value due to an increased probability of an empty site
      being occupied. We show that altruists are most favored in islands with an
      intermediate number of empty sites.

PMID- 18331457
TI  - Evolutionary responses to environmental heterogeneity in central american
      echinoid larvae: plastic versus constant phenotypes.
AB  - Do changes in food resources lead to evolutionary changes in phenotypic
      plasticity or in different constant phenotypes? I addressed this question by
      studying plasticity of larval feeding arms for "geminate species pairs" in three
      echinoid genera. These closely related species were geographically isolated when
      the Panamanian Isthmus raised 2.8-3.1 million years ago, creating two different
      food level environments: high but variable food levels in the eastern Pacific
      versus chronically low food levels in the western Caribbean. I reared larvae of
      geminate species in different replicated food environments for 10 days
      postfertilization, collected morphological measurements of individual arm and
      body lengths, and calculated degrees of plasticity of relative arm length for
      each species. In contrast to previous studies with temperate echinoids, there was
      no significant plasticity of arm length in either the Pacific or Caribbean
      species considered here. Caribbean species, however, had significantly longer
      relative arm lengths than Pacific species, regardless of food levels. These
      results suggest that historical changes in food levels have led to the evolution
      of constant rather than plastic differences between Pacific and Caribbean
      echinoids. The evolution of plasticity may be limited by the timing of
      reproduction or by egg size in this system.

PMID- 18331458
TI  - Evolution of thermotolerance in seasonal environments: the effects of annual
      temperature variation and life-history timing in Wyeomyia smithii.
AB  - In organisms with complex life cycles, the adaptive value of thermotolerance
      depends on life-history timing and seasonal temperature profiles. We illustrate
      this concept by examining variation in annual thermal environments and thermal
      acclimation among four geographic populations of the pitcher plant mosquito. Only
      diapausing larvae experience winter, whereas both postdiapause and nondiapause
      adults occur only during the growing season. Thus, adults experience transient
      cold stress primarily during the spring. We show that adult cold tolerance (chill
      coma recovery) is enhanced in spring-like conditions via thermal acclimation but
      is unaffected by diapause state. Moreover, adult mosquitoes from northern
      populations were more cold tolerant than those from southern populations largely
      because acclimation responses were steeper in the north. In contrast to cold
      tolerance, there was no significant acclimation of heat tolerance (heat
      knockdown), and no significant differences in heat tolerance between northern and
      southern populations. Field temperature data show that because of evolved
      differences in diapause timing, adult exposure to cold stress is remarkably
      consistent across geography. This suggests that geographic variation in cold
      tolerance may not be the result of direct selection on adults. Our results
      illustrate the importance of the interplay between phenological and thermal
      adaptation for understanding variation along climatic gradients.

PMID- 18331459
TI  - Hybrid zone origins, species boundaries, and the evolution of wing-pattern
      diversity in a polytypic species complex of North American admiral butterflies
      (Nymphalidae: Limenitis).
AB  - Hybrid zones present opportunities to study the effects of gene flow, selection,
      and recombination in natural populations and, thus, provide insights into the
      genetic and phenotypic changes that occur early in speciation. Here we
      investigate a hybrid zone between mimetic (Limenitis arthemis astyanax) and
      nonmimetic (Limenitis arthemis arthemis) populations of admiral butterflies using
      DNA sequence variation from mtDNA and seven nuclear gene loci. We find three
      distinct mitochondrial clades within this complex, and observe a strong overall
      concordance between wing-pattern phenotypes and mitochondrial variation. Nuclear
      gene genealogies, in contrast, revealed no evidence of exclusivity for either
      wing-pattern phenotype, suggesting incomplete barriers to gene exchange and/or
      insufficient time for lineage sorting. Coalescent simulations indicate that gene
      flow between these two subspecies is highly asymmetric, with the majority of
      migration occurring from mimetic into nonmimetic populations. Selective sweeps of
      alleles responsible for mimetic phenotypes may have occurred more than once when
      mimetic and nonmimetic Limenitis occurred together in the presence of the model
      (Battus philenor).

PMID- 18331460
TI  - Testing the grain-size model for the evolution of phenotypic plasticity.
AB  - Phenotypic plasticity is the ability of a genotype to modify its phenotypic
      characteristics in response to different environments. Theory predicts that
      adaptive plasticity should primarily evolve in organisms that experience
      heterogeneous environments. An organism's dispersal rate is a key component in
      these models, because the degree of dispersal partly determines the extent of
      environmental heterogeneity. Here, I provide the first large-scale test of the
      theoretical prediction that phenotypic plasticity evolves in association with
      dispersal rate using meta-analysis of data from 258 experiments from the
      literature on plasticity in marine invertebrates. In line with predictions,
      phenotypic plasticity is generally greater in species with higher dispersal
      rates, suggesting that dispersal and environmental heterogeneity are important
      selective agents for evolution of plasticity in marine habitats.

PMID- 18331461
TI  - Inferring population history and demography using microsatellites, mitochondrial
      DNA, and major histocompatibility complex (MHC) genes.
AB  - Microsatellites and mitochondrial DNA (mtDNA) have traditionally been used in
      population genetics because of their variability and presumed neutrality, whereas
      genes of the major histocompatibility complex (MHC) are increasingly of interest
      because strong selective pressures shape their standing variation. Despite the
      potential for MHC genes, microsatellites, and mtDNA sequences to complement one
      another in deciphering population history and demography, the three are rarely
      used in tandem. Here we report on MHC, microsatellite, and mtDNA variability in a
      single large population of the eastern tiger salamander (Ambystoma tigrinum
      tigrinum). We use the mtDNA mismatch distribution and, on microsatellite data,
      the imbalance index and bottleneck tests to infer aspects of population history
      and demography. Haplotype and allelic variation was high at all loci surveyed,
      and heterozygosity was high at the nuclear loci. We find concordance among
      neutral molecular markers that suggests our study population originated from post
      Pleistocene expansions of multiple, fragmented sources that shared few migrants.
      Differences in N(e) estimates derived from haploid and diploid genetic markers
      are potentially attributable to secondary contact among source populations that
      experienced rapid mtDNA divergence and comparatively low levels of nuclear DNA
      divergence. We find strong evidence of natural selection acting on MHC genes and
      estimate long-term effective population sizes (N(e)) that are very large, making
      small selection intensities significant evolutionary forces in this population.

PMID- 18331462
TI  - Asimadoline, a kappa-opioid agonist, and satiation in functional dyspepsia.
AB  - BACKGROUND: Asimadoline, a kappa-opioid agonist, reduces visceral sensitivity in
      experimental animal models and may decrease satiation and postprandial fullness
      in healthy individuals. However, its effect on satiation in functional dyspepsia
      is unclear, and any symptom benefit has not been explored. AIM: To evaluate the
      effects of asimadoline on satiation volume and postchallenge symptoms in
      functional dyspepsia. METHODS: A randomized, double-blind trial evaluated gastric
      satiation and symptoms before and after 8 weeks of asimadoline 0.5 mg (n = 13) or
      1.0 mg (n = 13) or placebo (n = 14) b.d. in patients with functional dyspepsia
      (Rome II). Gastrointestinal Symptom Rating Scale and Nepean Dyspepsia Index were
      used to assess symptoms during the 8-week treatment. RESULTS: Over 8 weeks of
      treatment, asimadoline had no significant effect on maximum-tolerated volume or
      aggregate symptom score with nutrient drink challenge, and on the mean of the
      total daily symptom severity score compared to placebo. In a post hoc analysis,
      asimadoline 0.5 mg significantly increased the maximum-tolerated volume (1217 mL
      +/- 90.2) compared to placebo (807 mL +/- 111.8) in patients with higher
      postprandial fullness scores (P = 0.01). CONCLUSION: Asimadoline overall did not
      significantly alter maximum-tolerated volume, symptoms postnutrient challenge or
      symptoms over 8 weeks in functional dyspepsia.

PMID- 18331463
TI  - Time trends in first-diagnosis rates of colorectal adenomas: a 24-year population
      based study.
AB  - BACKGROUND: Little is known about the descriptive epidemiology of colorectal
      adenomas diagnosed in the population. AIM: To describe time trends in the rate of
      first diagnosis of colorectal adenomas and estimate the proportion of adenoma
      bearing individuals detected over a 24-year period. METHODS: A total of 11,027
      patients were first-diagnosed with colorectal adenomas among Cote-d'Or residents
      (France) between 1976 and 1999. Annual percentage changes were estimated using a
      Poisson regression model. The proportion of diagnosed adenoma-bearing individuals
      was estimated using the prevalence of adenomas in an autopsy study performed in
      the area. RESULTS: Standardized diagnosis rates were 89.6/100,000 men and
      50.3/100,000 women. During the period 1976-1993, diagnosis rates significantly
      increased with annual percentage changes in men and women of respectively +17.1%
      and +22.3% for proximal adenomas, +7.5% and +9.1% for distal adenomas and +7.2%
      and +8.0% for advanced adenomas. Changes were less marked during the period 1994
      1999. The estimated proportion of adenoma-bearing individuals diagnosed during
      the 24-year period was 20.0% in men and 16.0% in women. CONCLUSION: Despite a
      marked increase in the rate of first adenoma diagnosis, the proportion of
      diagnosed adenoma-bearing individuals seems too low to induce a significant
      decrease in colorectal cancer incidence.

PMID- 18331464
TI  - Review article: blood platelet number and function in chronic liver disease and
      cirrhosis.
AB  - BACKGROUND: The liver plays a central role in coagulation and fibrinolysis but is
      also closely intertwined with the function and number of blood platelets. AIM: To
      describe and integrate all literature concerning blood platelets and liver
      disease by performing a thorough literature research. METHODS: A thorough
      literature research on 'blood platelets' and 'liver disease' was performed.
      RESULTS: Thrombocytopenia is a marked feature of chronic liver disease and
      cirrhosis. Traditionally, this thrombocytopenia was attributed to passive
      platelet sequestration in the spleen. More recent insights suggest an increased
      platelet breakdown and to a lesser extent decreased platelet production plays a
      more important role. Besides the reduction in number, other studies suggest
      functional platelet defects. This platelet dysfunction is probably both intrinsic
      to the platelets and secondary to soluble plasma factors. It reflects not only a
      decrease in aggregability, but also an activation of the intrinsic inhibitory
      pathways. The net effect, finally, is a decreased platelet function in the
      various types of chronic liver diseases and cirrhosis. Finally, recent data
      suggest that platelets are not only affected by but can also contribute to the
      liver disease process, as for instance, in viral hepatitis and cholestatic liver
      disease. CONCLUSION: Platelet research in liver disease is a growing area of
      investigation and could provide new pathophysiological insights.

PMID- 18331465
TI  - Probiotic Lactobacillus reuteri promotes TNF-induced apoptosis in human myeloid
      leukemia-derived cells by modulation of NF-kappaB and MAPK signalling.
AB  - The molecular mechanisms of pro-apoptotic effects of human-derived Lactobacillus
      reuteri ATCC PTA 6475 were investigated in this study. L. reuteri secretes
      factors that potentiate apoptosis in myeloid leukemia-derived cells induced by
      tumour necrosis factor (TNF), as indicated by intracellular esterase activity,
      terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end
      labelling assays and poly (ADP-ribose) polymerase cleavage. L. reuteri
      downregulated nuclear factor-kappaB (NF-kappaB)-dependent gene products that
      mediate cell proliferation (Cox-2, cyclin D1) and cell survival (Bcl-2, Bcl-xL).
      L. reuteri suppressed TNF-induced NF-kappaB activation, including NF-kappaB
      dependent reporter gene expression in a dose-and time-dependent manner. L.
      reuteri stabilized degradation of IkappaBalpha and inhibited nuclear
      translocation of p65 (RelA). Although phosphorylation of IkappaBalpha was not
      affected, subsequent polyubiquitination necessary for regulated IkappaBalpha
      degradation was abrogated by L. reuteri. In addition, L. reuteri promoted
      apoptosis by enhancing mitogen-activated protein kinase (MAPK) activities
      including c-Jun N-terminal kinase and p38 MAPK. In contrast, L. reuteri
      suppressed extracellular signal-regulated kinases 1/2 in TNF-activated myeloid
      cells. L. reuteri may regulate cell proliferation by promoting apoptosis of
      activated immune cells via inhibition of IkappaBalpha ubiquitination and
      enhancing pro-apoptotic MAPK signalling. An improved understanding of L. reuteri
      mediated effects on apoptotic signalling pathways may facilitate development of
      future probiotics-based regimens for prevention of colorectal cancer and
      inflammatory bowel disease.

PMID- 18331466
TI  - Mycobacterial infection induces the secretion of high-mobility group box 1
      protein.
AB  - High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that
      acts as a pro-inflammatory cytokine and is released by monocytes and macrophages.
      Necrotic cells also release HMGB1 at the site of tissue damage which induces a
      variety of cellular responses, including the expression of pro-inflammatory
      mediators. This study investigated the secretion of HMGB1 in mycobacterial
      infection by macrophages in vitro and in the lungs of infected guinea pigs. We
      observed that infection by mycobacterium effectively induced HMGB1 release in
      both macrophage and monocytic cell cultures. Culture filtrate proteins from
      Mycobacterium tuberculosis induced maximum release of HMGB1 compared with
      different subcellular fractions of mycobacterium. We demonstrated that HMGB1 is
      released in lungs during infection of M. tuberculosis in guinea pigs and
      increased HMGB1 secretion in lungs of guinea pigs was delayed by prior
      vaccination with Mycobacterium bovis BCG. The secretion of cytokines like tumour
      necrosis factor alpha (TNF-alpha) and Interleukin-1beta was significantly
      increased when M. bovis BCG-infected cultures of J774A.1 cells were incubated
      with HMGB1. Among different mycobacterial toll-like receptor ligands, heat-shock
      protein 65 (HSP65) was found to be more potent in inducing HMGB1 secretion in RAW
      264.7 cells. Pharmacological suppression of p38 or extracellular signal-regulated
      kinase 1/2 mitogen-activated protein kinases with specific inhibitors failed to
      inhibit HSP65-induced HMGB1 release, but inhibition of c-Jun NH(2)-terminal
      kinase activation attenuated HMGB1 release. Inhibition of the inducible NO
      synthase and neutralizing antibodies against TNF-alpha also reduced HMGB1 release
      stimulated by HSP65. We conclude that HMGB1 is secreted by macrophages during
      tuberculosis and it may act as a signal of tissue or cellular injury and enhances
      immune response.

PMID- 18331467
TI  - Subversion of actin dynamics by EspM effectors of attaching and effacing
      bacterial pathogens.
AB  - Rho GTPases are common targets of bacterial toxins and type III secretion system
      effectors. IpgB1 and IpgB2 of Shigella and Map of enteropathogenic (EPEC) and
      enterohemorrhagic (EHEC) Escherichia coli were recently grouped together on the
      basis that they share a conserved WxxxE motif. In this study, we characterized
      six WxxxE effectors from attaching and effacing pathogens: TrcA and EspM1 of EPEC
      strain B171, EspM1 and EspM2 of EHEC strain Sakai and EspM2 and EspM3 of
      Citrobacter rodentium. We show that EspM2 triggers formation of global parallel
      stress fibres, TrcA and EspM1 induce formation of localized parallel stress
      fibres and EspM3 triggers formation of localized radial stress fibres. Using
      EspM2 and EspM3 as model effectors, we report that while substituting the
      conserved Trp with Ala abolished activity, conservative Trp to Tyr or Glu to Asp
      substitutions did not affect stress-fibre formation. We show, using dominant
      negative constructs and chemical inhibitors, that the activity of EspM2 and EspM3
      is RhoA and ROCK-dependent. Using Rhotekin pull-downs, we have shown that EspM2
      and EspM3 activate RhoA; translocation of EspM2 and EspM3 triggered
      phosphorylation of cofilin. These results suggest that the EspM effectors
      modulate actin dynamics by activating the RhoA signalling pathway.

PMID- 18331468
TI  - Inhibition of ROCK activity allows InlF-mediated invasion and increased virulence
      of Listeria monocytogenes.
AB  - Listeria monocytogenes is an intracellular bacterial pathogen that causes life
      threatening disease. The mechanisms used by L. monocytogenes to invade non
      professional phagocytic cells are not fully understood. In addition to the
      requirement of bacterial determinants, host cell conditions profoundly influence
      infection. Here, we have shown that inhibition of the RhoA/ROCK pathway by
      pharmacological inhibitors or RNA interference results in increased L.
      monocytogenes invasion of murine fibroblasts and hepatocytes. InlF, a member of
      the internalin multigene family with no known function, was identified as a L.
      monocytogenes-specific factor mediating increased host cell binding and entry.
      Conversely, activation of RhoA/ROCK activity resulted in decreased L.
      monocytogenes adhesion and invasion. Furthermore, virulence of wild-type bacteria
      during infection of mice was significantly increased upon inhibition of ROCK
      activity, whereas colonization and virulence of an inlF deletion mutant was not
      affected, thus supporting a role for InlF as a functional virulence determinant
      in vivo under specific conditions. In addition, inhibition of ROCK activity in
      human-derived cells enhanced either bacterial adhesion or adhesion and entry in
      an InlF-independent manner, further suggesting a host species or cell type
      specific role for InlF and that additional bacterial determinants are involved in
      mediating ROCK-regulated invasion of human cells.

PMID- 18331469
TI  - Regulation of transcription by acetate in Escherichia coli: in vivo and in vitro
      comparisons.
AB  - Acetate, even at neutral pH, induces changes in gene expression that allow
      Escherichia coli to adapt to the diverse chemical stresses of the
      gastrointestinal tract. These include differential effects on transcription,
      including both activation and repression. The in vivo studies presented here show
      that cyclopropane fatty acid synthase transcription induced by neutral acetate
      proceeds via both the sigma70 and sigma38 forms of RNA polymerase. Upstream DNA
      elements are required in both cases, but in vitro studies demonstrate that the
      binding of regulatory factors is not needed. Sigma70 promoters respond towards
      acetate with very significant differences in vitro, with effects ranging from
      inhibition to lack of effect to weak stimulation to strong stimulation. By
      contrast, the effects of acetate on sigma38 transcription at these same promoters
      in vitro are generally stimulatory. Thus, acetate directly alters transcription
      complexes in vitro in ways that lead to significant differential transcription,
      contributing to the diverse effects that are known to allow adaptation in vivo.

PMID- 18331470
TI  - RosE represses Std fimbrial expression in Salmonella enterica serotype
      Typhimurium.
AB  - The Salmonella enterica serotype Typhimurium (S. typhimurium) genome contains a
      large repertoire of putative fimbrial operons that remain poorly characterized
      because they are not expressed in vitro. In this study, insertions that induced
      expression of the putative stdABCD fimbrial operon were identified from a random
      bank of transposon mutants by screening with immuno-magnetic particles for ligand
      expression (SIMPLE). Transposon insertions upstream of csgC and lrhA or within
      dam, setB and STM4463 (renamed rosE) resulted in expression of StdA and its
      assembly into fimbrial filaments on the cell surface. RosE is a novel negative
      regulator of Std fimbrial expression as indicated by its repression of a
      std::lacZ reporter construct and by binding of the purified protein to a DNA
      region upstream of the stdA start codon. Expression of Std fimbriae in the rosE
      mutant resulted in increased attachment of S. typhimurium to human colonic
      epithelial cell lines (T-84 and CaCo-2). A rosE mutant exhibited a reduced
      ability to compete with virulent S. typhimurium for colonization of murine
      organs, while no defect was observed when both competing strains carried a stdAB
      deletion. These data suggest that a tight control of Std fimbrial expression
      mediated by RosE is required during host pathogen interaction.

PMID- 18331471
TI  - The conserved PA14 domain of cell wall-associated fungal adhesins governs their
      glycan-binding specificity.
AB  - Yeast cell wall-associated, lectin-like adhesins form large families that mediate
      flocculation and host cell recognition. The glycan specificity of individual
      adhesins is largely unknown. Zupancic et al. (this issue of Molecular
      Microbiology) used glycan microarrays to compare the glycan-binding
      characteristics of individual adhesins (Epa proteins) of the pathogenic yeast
      Candida glabrata produced in the non-adherent yeast Saccharomyces cerevisiae. By
      sequence swapping between the conserved PA14 domains of two related Epa proteins,
      they identified a pentapeptide that determines binding specificity and cell
      adherence and is located on a surface loop of the known crystal structure of the
      anthrax toxin PA14 domain.

PMID- 18331472
TI  - Modus operandi of the bacterial RNA polymerase containing the sigma54 promoter
      specificity factor.
AB  - Bacterial sigma (sigma) factors confer gene specificity upon the RNA polymerase,
      the central enzyme that catalyses gene transcription. The binding of the
      alternative sigma factor sigma(54) confers upon the RNA polymerase special
      functional and regulatory properties, making it suited for control of several
      major adaptive responses. Here, we summarize our current understanding of the
      interactions the sigma(54) factor makes with the bacterial transcription
      machinery.

PMID- 18331473
TI  - Characterization of an acyl-CoA: carboxylate CoA-transferase from Aspergillus
      nidulans involved in propionyl-CoA detoxification.
AB  - Filamentous fungi metabolize toxic propionyl-CoA via the methylcitrate cycle.
      Disruption of the methylcitrate synthase gene leads to an accumulation of
      propionyl-CoA and attenuates virulence of Aspergillus fumigatus. However,
      addition of acetate, but not ethanol, to propionate-containing medium strongly
      reduces the accumulation of propionyl-CoA and restores growth of the
      methylcitrate synthase mutant. Therefore, the existence of a CoA-transferase was
      postulated, which transfers the CoASH moiety from propionyl-CoA to acetate and,
      thereby, detoxifying the cell. In this study, we purified the responsible protein
      from Aspergillus nidulans and characterized its biochemical properties. The
      enzyme used succinyl-, propionyl- and acetyl-CoA as CoASH donors and the
      corresponding acids as acceptor molecules. Although the protein displayed high
      sequence similarity to acetyl-CoA hydrolases this activity was hardly detectable.
      We additionally identified and deleted the coding DNA sequence of the CoA
      transferase. The mutant displayed weak phenotypes in the presence of propionate
      and behaved like the wild type when no propionate was present. However, when a
      double-deletion mutant defective in both methylcitrate synthase and CoA
      transferase was constructed, the resulting strain was unable to grow on media
      containing acetate and propionate as sole carbon sources, which confirmed the in
      vivo activity of the CoA-transferase.

PMID- 18331474
TI  - The role of actin, fimbrin and endocytosis in growth of hyphae in Aspergillus
      nidulans.
AB  - Filamentous fungi are ideal systems to study the process of polarized growth, as
      their life cycle is dominated by hyphal growth exclusively at the cell apex. The
      actin cytoskeleton plays an important role in this growth. Until now, there have
      been no tools to visualize actin or the actin-binding protein fimbrin in live
      cells of a filamentous fungus. We investigated the roles of actin (ActA) and
      fimbrin (FimA) in hyphal growth in Aspergillus nidulans. We examined the
      localization of ActA::GFP and FimA::GFP in live cells, and each displayed a
      similar localization pattern. In actively growing hyphae, cortical ActA::GFP and
      FimA::GFP patches were highly mobile throughout the hypha and were concentrated
      near hyphal apices. A patch-depleted zone occupied the apical 0.5 microm of
      growing hypha. Both FimA::GFP and Act::GFP also localize transiently to septa.
      Movement and later localization of both was compromised after cytochalasin
      treatment. Disruption of fimA resulted in delayed polarity establishment during
      conidium germination, abnormal hyphal growth and endocytosis defects in apolar
      cells. Endocytosis was severely impaired in apolar fimA disruption cells. Our
      data support a novel apical recycling model which indicates a critical role for
      actin patch-mediated endocytosis to maintain polarized growth at the apex.

PMID- 18331475
TI  - Anti-apoptotic effect of Mao-B inhibitor PF9601N [N-(2-propynyl)-2-(5-benzyloxy
      indolyl) methylamine] is mediated by p53 pathway inhibition in MPP+-treated SH
      SY5Y human dopaminergic cells.
AB  - PF9601N [N-(2-propynyl) 2-(5-benzyloxyindol) methylamine] is a non-amphetamine
      type MAO-B inhibitor that has shown neuroprotective properties in vivo using
      different experimental models of Parkinson's disease. The mechanisms underlying
      its neuroprotective effects are poorly understood, but appear to be independent
      of MAO-B inhibition. We have studied its neuroprotective properties using the
      human SH-SY5Y dopaminergic cell line exposed to 1-methyl-4-phenylpyridinium
      (MPP(+)), a cellular model of Parkinson's disease. PF9601N pre-treatment
      significantly reduced MPP(+)-induced cell death and decreased the activation of
      one of the main executioner caspases, caspase-3. MPP(+) induced stabilization of
      transcription factor p53, which led to increased levels of this transcription
      factor, its nuclear translocation and transactivation of p53 response elements.
      PF9601N prevented this increase, thus reducing its transcriptional activity.
      Additional results showed that p53 may mediate its pro-apoptotic actions through
      caspase-2 under our experimental conditions. PUMA-alpha may also contribute to
      the p53-induced cell death. Since PF9601N significantly reduced MPP(+)-induced
      caspase-2 activity and PUMA-alpha levels, this reduction may lead to increased
      cell survival. Thus, PF9601N is a novel molecule with an apparently novel
      mechanism of action which has a promising potential as a therapeutic agent in the
      treatment of neurodegenerative diseases.

PMID- 18331476
TI  - Characterization of signaling pathway for the translocation of neuronal nitric
      oxide synthase to the plasma membrane by PACAP.
AB  - In the central nervous system, the activation of neuronal nitric oxide synthase
      (nNOS) is closely associated with activation of NMDA receptor, and trafficking of
      nNOS may be a prerequisite for efficient NO production at synapses. We recently
      demonstrated that pituitary adenylate cyclase activating polypeptide (PACAP) and
      NMDA synergistically caused the translocation of nNOS to the membrane and
      stimulated NO production in PC12 (pheochromocytoma) cells. However, the
      mechanisms responsible for trafficking and activation of nNOS are largely
      unknown. To address these issues, here we constructed a yellow fluorescent
      protein (YFP)-tagged nNOS N-terminal (1-299 a.a.) mutant, nNOSNT-YFP, and
      visualized its translocation in PC12 cells stably expressing it. PACAP enhanced
      the translocation synergistically with NMDA in a time- and concentration
      dependent manner. The translocation was blocked by inhibitors of protein kinase A
      (PKA), protein kinase C (PKC), and Src kinase; and the effect of PACAP could be
      replaced with PKA and PKC activators. The beta-finger region in the PSD-95/disc
      large/zonula occludens-1 domain of nNOS was required for the translocation of
      nNOS and its interaction with post-synaptic density-95 (PSD-95), and NO formation
      was attenuated by dominant negative nNOSNT-YFP. These results demonstrate that
      PACAP stimulated nNOS translocation mediated by PKA and PKC via PAC(1)-receptor
      (a PACAP receptor) and suggest cross-talk between PACAP and NMDA for nNOS
      activation by Src-dependent phosphorylation of NMDA receptors.

PMID- 18331477
TI  - Sustained saturating level of glycine induces changes in NR2B-containing-NMDA
      receptor localization in the CA1 region of the hippocampus.
AB  - Post-synaptic actions of glycine are terminated by specialized transporters.
      There are two genes encoding glycine transporters, GlyT1 and GlyT2. Glycine acts
      as a co-agonist at N-methyl-d-aspartate glutamatergic receptors (NMDARs).
      Blockage of GlyT1 enhances NMDAR function by controlling ambient glycine
      concentrations. Using whole-cell patch-clamp recordings of acute hippocampal
      slices, we investigated NMDAR kinetics of CA1 pyramidal neurons of mice
      expressing 50% of GlyT1 (GlyT1+/-). In this study, we report that the glycine
      modulatory site of the NMDAR at CA1 synapses is saturated in GlyT1+/- but not in
      wild-type (WT) mice. We also found that the effect of ifenprodil, a highly
      selective NR2B-containing-NMDAR antagonist, is significantly reduced at CA1
      synapses in GlyT1+/- compared to WT mice while immunoblotting experiments do not
      show significant differences for NR1, NR2A-B-C-D subunits in both types of mice,
      suggesting alteration in NR2B-containing-NMDAR localization under a state of
      chronic saturating level of endogenous glycine. Using a pharmacological approach
      with MK-801 and DL-TBOA, we discriminated synaptic vis-a-vis extra-synaptic
      NMDARs. We found that NR2B-containing-NMDARs are expressed at a higher level in
      the extra-synaptic area of CA1 pyramidal neurons from GlyT1+/- compared to WT
      mice. Our results demonstrate that chronic saturating level of glycine induces
      significant changes in NMDAR localization and kinetic. Therefore, results from
      our study should help to gain a better understanding of the role of glycine in
      pathological conditions.

PMID- 18331478
TI  - Moving ahead in 2008.

PMID- 18331479
TI  - Nursing diagnosis: is it time for a new definition?
AB  - PURPOSE: The Diagnosis Development Committee (DDC) of NANDA International
      frequently receives proposed "physiologic" and "surveillance diagnosis"
      submissions that may not meet the current definition of nursing diagnosis (NANDA,
      2007, p. 332). There has been a request for a vote on newly proposed definitions
      of nursing diagnosis, risk diagnosis, and syndromes. The purpose of this article
      is to provide information which enables members and interested nurses to continue
      the dialogue and to share their thoughts and also to consider the thoughts and
      information generated by the participants in the NANDA-I interest survey on the
      definition of nursing diagnoses. DATA SOURCES: An electronic survey of the
      current NANDA-I definitions, and potential changes to those definitions, was
      distributed via the NANDA-I Web site. This article summarizes the overall
      findings of that survey and provides an overview of commentary received from the
      269 participants. CONCLUSIONS: It is necessary to continue the dialogue on this
      important decision and to provide a mechanism for input from members and
      interested nurses before reaching any conclusions on this subject. NURSING
      IMPLICATIONS: NANDA-I has been recognized as the leader in the development and
      implementation of nursing diagnoses and must act responsibly in assessing the
      changing and emerging trends in nursing practice and in responding to these
      trends.

PMID- 18331480
TI  - An exemplar of the use of NNN language in developing evidence-based practice
      guidelines.
AB  - PURPOSE: To explore the use of standardized language, NNN, in the development of
      evidence-based practice (EBP). DATA SOURCES: Published research and texts on
      family interventions, nursing diagnoses (NANDA-I), nursing interventions (NIC),
      and nursing outcomes (NOC). DATA ANALYSIS: Research literature was summarized and
      synthesized to determine levels of evidence for the NIC intervention Family
      Integrity Promotion. CONCLUSIONS: The authors advocate that a "standards of
      practice" category of levels of evidence be adopted for interventions not
      amenable to randomized controlled trials or for which a body of research has not
      been developed. Priorities for nursing family intervention research are
      identified. IMPLICATIONS FOR NURSING PRACTICE: The use of NANDA-I nursing
      diagnoses, NIC interventions, and NOC outcomes (NNN language) as research
      frameworks will facilitate the development of EBP guidelines and the use of
      appropriate outcome measures.

PMID- 18331481
TI  - Testing the Q-DIO as an instrument to measure the documented quality of nursing
      diagnoses, interventions, and outcomes.
AB  - PURPOSE: To describe pilot testing of Quality of Diagnoses, Interventions and
      Outcomes (Q-DIO), an instrument to measure quality of nursing documentation.
      DESIGN: Instrument testing was performed using a random, stratified sample of 60
      nursing documentations representing hospital nursing with and without
      implementation of standardized nursing language (30 for both strata) in a Swiss
      General Acute Hospital. METHODS: Internal consistency and intrarater and
      interrater reliabilities were tested. Through item analyses, the grades of
      difficulty and the discrimination validity of items were evaluated. FINDINGS:
      Internal consistency of nursing diagnoses as process produced Cronbach's alpha
      .83; nursing diagnoses as product .98; nursing interventions .90; and nursing
      sensitive patient outcomes .99. With Kappas of .95, the intrarater and interrater
      reliabilities were good. Criteria for the grades of difficulty of items and
      discrimination validity were well met. The results of this study suggest that Q
      DIO is a reliable instrument to measure the documentation quality of nursing
      diagnoses, interventions, and outcomes. Further testing of Q-DIO in other
      settings is recommended.

PMID- 18331482
TI  - The need for international nursing diagnosis research and a theoretical
      framework.
AB  - PURPOSE: To describe the need for nursing diagnosis research and a theoretical
      framework for such research. DATA SOURCES: A linguistics theory served as the
      foundation for the theoretical framework. DATA SYNTHESIS: Reasons for additional
      nursing diagnosis research are: (a) file names are needed for implementation of
      electronic health records, (b) international consensus is needed for an
      international classification, and (c) continuous changes occur in clinical
      practice. A theoretical framework used by the author is explained. CONCLUSIONS:
      Theoretical frameworks provide support for nursing diagnosis research.
      Linguistics theory served as an appropriate exemplar theory to support nursing
      research. IMPLICATION: Additional nursing diagnosis studies based upon a
      theoretical framework are needed and linguistics theory can provide an
      appropriate structure for this research.

PMID- 18331483
TI  - Some artefacts of the approaches with the discretization in near-field optics
      calculations.
AB  - This article is devoted to an observation artefact arising in near-field optical
      calculations by methods with the discretization of a scattering object and the
      substitution of separated dipoles instead of discretizing meshes. It is discussed
      that such an artificial discretization gives within the object a non-monotonously
      changing field on the scale of the discretizing mesh size, which propagates from
      the object to a distance of the same order of magnitude as the mesh size in
      contrast to the real situation where such a non-monotonously changing fields
      exist on the scale of a real atomic lattice. If such a non-monotonously changing
      field exists in the observation plane where the picture is calculated, the choice
      of the observation points can change the obtained picture remarkably.

PMID- 18331484
TI  - Local excitation and interference of surface phonon polaritons studied by near
      field infrared microscopy.
AB  - We demonstrate that mid-infrared surface phonon polariton excitation, propagation
      and interference can be studied by scattering-type near-field optical microscopy
      (s-SNOM). In our experiments we image surface phonon polaritons (SPPs)
      propagating on flat SiC crystals. They are excited by weakly focused illumination
      of single or closely spaced metal disks we fabricated on the SiC surface by
      conventional photolithography. SPP imaging is performed by pseudo-heterodyne
      interferometric detection of infrared light scattered by the metal tip of our s
      SNOM. The pseudo-heterodyne technique simultaneously yields optical amplitude and
      phase images which allows us to measure the SPP wave vector--including its sign-
      and the propagation length and further to study SPP interference. High resolution
      imaging of SPPs could be applied to investigate for example SPP focusing or heat
      transfer by SPPs in low dimensional nanostructures.

PMID- 18331485
TI  - Plasmonic devices with controllable resonances--an avenue towards high-speed and
      mass fabrication of optical meta-materials.
AB  - We report on the fabrication of plasmonic devices with adjustable resonances in
      the visible portion employing a thermal lithography method. The genuine approach
      enables the fabrication of nanostructured pattern at a spatial resolution
      comparable to other nanofabrication techniques, but at significantly larger
      speeds and over extended spatial domains. The fabricated structures consisted in
      periodically arranged nanoholes in a silver thin film and supported localized
      plasmon resonance (LPR) in the vicinity of 370 nm. Results from measured spectral
      properties were in good agreement with simulations based on rigorous diffraction
      theory. The method was evaluated towards a potential application to realize large
      scale meta-materials with effective negative refractive index in the visible.

PMID- 18331486
TI  - Nano-Raman mapping of a porous glass-ceramic SERS substrate in collection mode.
AB  - Porous glass-ceramics is an extremely important material to be used in
      combination with metallic nanolayers as a Surface-Enhanced Raman Scattering
      (SERS) substrate for biological and chemical analysis, demonstrating excellent
      biocompatibility and chemical inertness. These materials show their own Raman
      background signal lateral distribution, mostly from crystalline skeleton, which
      has to be considered. A nano-Raman setup using the optical fibre of a Scanning
      Near-Field Optical Microscope (SNOM), working in collection mode, is described
      and applied for mapping of such glass-ceramic. The collected Raman signal of Ti
      and P containing phase distribution in this near-field geometry reaches spatial
      resolution around 50 nm.

PMID- 18331487
TI  - Influence of chopped laser light onto the electronic transport through atomic
      sized contacts.
AB  - This paper reports on the influence of laser irradiation onto the electrical
      conductance of gold nanocontacts established with the mechanically controllable
      breakjunction technique. We concentrate here on the study of reversible
      conductance changes which can be as high as 200%. We investigate the dependence
      on the initial conductance of the contacts, the wavelength, the intensity and
      position of the laser spot with respect to the sample. Under most conditions an
      enhancement of the conductance is observed. We discuss several physical
      mechanisms which might contribute to the observed effect including thermal
      expansion, rectification and photon-assisted transport. We conclude that thermal
      expansion is not the dominating one.

PMID- 18331488
TI  - Towards nonlinear plasmonic devices based on metallic nanorods.
AB  - The nonlinear optical properties of gold nanorod arrays have been studied with a
      two-colour continuously working (CW) pump-probe spectroscopy. The hybridization
      of the nanorod arrays with a nonlinear polymer (poly-3BCMU) has been investigated
      for the purposes of active photonic component design. The sensitivity of the
      plasmonic resonances of the hybrid nanostructured system to pump-induced changes
      in the refractive index of the polymer surroundings has been used to control the
      optical extinction of the array. Both reversible and non-reversible behaviour has
      been observed reflecting the combined effects from the third-order nonlinear
      response of the hybrid metallo-dielectric system and post-photopolymerization
      triggered reactions in the polymer.

PMID- 18331489
TI  - Controlling the plasmon resonance of single metal nanoparticles by near-field
      anisotropic nanoscale photopolymerization.
AB  - We propose a new approach for tuning the Surface Plasmon (SP) resonance
      wavelength using hybrid nanoparticles. Our approach is based on nanoscale
      photopolymerization around metal nanoparticles. The enhanced optical near-field
      of silver nanoparticles triggers local photopolymerization. As a result, atomic
      force microscopy reveals two nanoscale polymerized lobes around nanoparticles,
      with a controlled effective index distribution. A spectral breaking degeneracy of
      surface plasmon resonance of the nanoparticles has been demonstrated by polarized
      extinction spectroscopy.

PMID- 18331490
TI  - Modelling of the near-field of metallic nanoparticle gratings: localized surface
      plasmon resonance and SERS applications.
AB  - We numerically study the influence of the shape of gold nanostructures on the
      spectral position of their localized surface plasmon resonance and on Surface
      Enhanced Raman Scattering efficiency. Calculations are performed using a Finite
      Difference Time-Domain (FDTD) method, whose accuracy for dispersive media is
      enhanced through the use of a Drude-Lorentz model. The relevance of this method
      is then pointed out by comparing the calculations with experimental data for both
      the plasmon resonance and the Raman signal enhancement. The influence of a thin
      layer of water is also investigated.

PMID- 18331491
TI  - Implementation of a bimorph-based aperture tapping-SNOM with an incubator to
      study the evolution of cultured living cells.
AB  - We present the implementation of a tapping-mode aperture scanning near-field
      optical microscope (Tapping-SNOM) to a Binder CB incubator (Istituto di Struttura
      della Materia, Rome, Italy). The microscope operates in the intermittent contact
      mode using a nonbent optical fibre allowing to reduce the perturbation exerted on
      the sample, while the incubator maintains a constant temperature, humidity and
      CO(2) level. This instrument can maintain and analyse in a controlled environment
      different samples, both organic and nonorganic. In particular, the Tapping-SNOM
      can study different cell lines at nanometric resolution and in physiological
      buffer, following the evolution of the living cells almost indefinitely. We will
      present several examples of the capabilities of the tapping scanning near-field
      optical microscope in the study of different lines of living cells, showing
      corresponding topographical, optical or phase-lag images of the live samples,
      evidencing the excellent stability, versatility and resolution of the system.

PMID- 18331492
TI  - SNOM on cell thin sections: observation of Jurkat and MDAMB453 cells.
AB  - In this study a comparison of scanning near-field optical microscopy with a
      traditional, well-known microscopic technique like transmission electron
      microscopy is discussed. To establish a reliable and comparable method for high
      resolution scanning near-field optical microscopy imaging of biological samples,
      the attention is focussed on cell sections. In particular, we present a study of
      ultrathin sections of Jurkat T-cells and MDAMB453 cells. We show the relationship
      among the scanning near-field optical microscopy (topographic and optical) images
      and the kind of embedding medium (resin), the sections thickness and the staining
      of the sample. For a complementary investigation atomic force microscopy
      measurements are carried out, as well. The study reveals that scanning near-field
      optical microscopy technique on opportunely prepared thin sections can be applied
      successfully for investigation of the interior of the cells. Scanning near-field
      optical microscopy and transmission electron microscopy allow to obtain
      different, however comparable, and complementary information of the cell sample.

PMID- 18331493
TI  - Study of surface plasmon polaritons near the photonic-bandgap edge for
      interphotonic band switching devices.
AB  - The photonic energy band structures near the bandgap edges of surface plasmon
      polariton in dielectric lattice structures on a smooth silver film were studied.
      At the bandgap edges, sharp changes of the surface plasmon polariton's
      transmittance arise owing to small changes in the refractive index around the
      lattice structure, which results in the band transition between the pass band and
      the stop band. On the analogy of 'the phase transition' between the surface
      plasmon polariton's conductive phase and the insulation phase, the surface
      plasmon polariton's phase diagram of the 1D lattice structure at a single
      frequency (lambda approximately 780 nm) with parameters of the pitch and the
      refractive index of lattice were investigated. At the boundary, the most
      sensitive transition was found between the second pass band and the first stop
      band, with the approximately 0.5 lattice filling factor. The surface plasmon
      polariton's phase state has been determined by far-field observation using an
      optical microscope.

PMID- 18331494
TI  - Caustics in a field negatively refracted at a plane interface.
AB  - An electromagnetic field radiated by a line source situated near a plane
      interface between a medium with positive refractive index and a medium with
      negative refractive index is considered by using the geometrical optics approach.
      Rays and wave fronts of the refracted field are constructed using Fermat's
      principle. It is shown that the negatively refracted rays intersecting in pairs
      create 2-fold caustics that meet at a cusp point. The cusp of the caustic is
      directed towards the interface for |n| > 1 and away from the interface for |n| <
      1, where n is the relative refractive index. It is also shown that wave fronts of
      the refracted field propagate towards the interface, in the direction from
      negative to positive optical path lengths.

PMID- 18331495
TI  - Molecular ordering in self-organized dye particles: polarized evanescent-field
      studies.
AB  - Self-organized rhodamine 6G particles prepared by wetting/dewetting process of an
      ethanol solution on a hydrophilic glass surface did show fluorescence without
      quenching. Polarized evanescent-field excitation showed that the molecule's
      transition moment within dye particles was oriented unidirectionally and parallel
      to the substrate surface. The deduced dye orientation showed correlation between
      adjacent particles, which implies a simultaneous aggregate growth from a common
      crystal seed grown in a possible 'arm' region connecting the adjacent droplets
      just before these droplets were disconnected upon solvent evaporation. The dye
      orientation of most particles pointed about 45 degrees off the dewetting
      direction. By contrast, the particles of another pi-conjugated NK1420 dye, J
      aggregates of which grow easily from an oversaturated solution, showed dye
      orientation along the dewetting direction preferably, still indicating the effect
      of self-organization, however based on a different mechanism.

PMID- 18331496
TI  - Regular molecular nano-dot patterns for RW-data storage in the optical near
      field.
AB  - In this contribution further steps to realize our concept of optical data storage
      in molecular nano-dots as storage bits are reported. A preparation method has
      been developed successfully to achieve regular nano-dot patterns of high density.
      This is considered a breakthrough because regularity is prerequisite for the use
      of nano-dots in storage media. Optical imaging of dot patterns and individual
      writing/reading access is realized by confocal and near-field optical microscopy
      (fluorescence detection mode). Examples for regular patterns at different dot
      densities are shown. Perspectives towards terabit per square inch density are
      outlined.

PMID- 18331497
TI  - Near-field investigation of porous silicon photoluminescence modification after
      oxidation in water.
AB  - We report on local photo-induced oxidation of porous silicon in water at room
      temperature. Starting from a nonluminescent sample, the oxidation process induces
      luminescence which was found to first increase and then decrease as a function of
      the oxidation time. A clear blue shift is also observed. This effect is believed
      to be owing to size modification of silicon nanocrystallites and thus is
      explained in terms of quantum confinement. Optical near-field images and spectrum
      are used to monitor the photoluminescence modifications after oxidation. As the
      photoluminescence can be widely tuned in wavelength and intensity, this method
      offers a way to pattern the emission properties of the sample.

PMID- 18331498
TI  - Influence of the light-scattering form factor on the Bragg diffraction patterns
      of arrays of metallic nanoparticles.
AB  - Accurate models for the light-scattering form factors of nanoparticles are of
      crucial importance to characterize the optical properties of the particles and to
      develop new photonic devices. Analytical or semi-empirical models exist for
      particles of spherical and cylindrical shape. The angular spectrum of scattering
      for particles of more complex shape is very complex and can only be obtained by
      numerical simulations. Moreover, the light scattering of metallic particles
      depends on many parameters as size, shape, optical constants, substrate and
      polarization of light. Experimental verification of the differential scattering
      cross-sections obtained from different calculation methods is always necessary.
      Measurements done on single nanoparticles are very sensitive to their local
      properties and the signal-to-noise ratio may be very poor. Arrays of identical
      particles illuminated by a planes waves produce Bragg diffraction and the
      resultant patterns depend on the averaged values of the form factors of the
      particles. In order to test the validity of models for the scattering form
      factor, we present an experimental setup capable of measuring Bragg diffraction
      patterns of arrays of nanoparticles in the visible and near-infrared regions of
      the spectrum. The approach is similar to that of X-ray diffraction of crystals.

PMID- 18331499
TI  - Numerical study of optical nanolithography using nanoscale bow-tie-shaped nano
      apertures.
AB  - Contact lithography using bow-tie-shaped nano-apertures was recently demonstrated
      to achieve nanometer scale resolution. In this work, the detailed field
      distributions in contact nanolithography are analyzed using finite difference
      time domain simulations. It was found that the high imaging contrast, which is
      necessary for successful lithography, is achieved close to the mask exit plane
      and decays quickly with the increase of the distance from the mask exit plane.
      Simulations are also performed for comparable regular-shaped apertures and
      different shape bow-tie apertures. Design rules are proposed to optimize the bow
      tie aperture for producing a sub-wavelength, high transmission field with high
      imaging contrast.

PMID- 18331500
TI  - SNOM images of X-ray radiographs at nano-scale stored in a thin layer of lithium
      fluoride.
AB  - In this work, we report a method to observe soft X-ray radiographs at nanoscale
      of various kind of samples, biological and metallic, stored in a thin layer of
      lithium fluoride, employing scanning near-field optical microscopy with an
      optical resolution that reaches 50 nm. Lithium fluoride material works as a novel
      image detector for X-ray nano-radiographs, due to the fact that extreme
      ultraviolet radiation and soft X-rays efficiently produce stable point defects
      emitting optically stimulated visible luminescence in a thin surface layer. The
      bi-dimensional distribution of the so-created defects depends on the local
      nanostructure of the investigated sample.

PMID- 18331501
TI  - Experimental research on the performance of a very-small-aperture laser.
AB  - Very-small-aperture lasers (VSALs) with different aperture shapes are fabricated.
      Their far-field and near-field performance is analyzed experimentally. The far
      field performance, including the threshold current, the slope efficiency, the
      lasing ability and the linear frequency modulation property, is found to be
      influenced by the front facet reflectivity. A new factor is tentatively proposed
      to analyze the lasing abilities of VSALs with different aperture shapes. This
      factor can diminish the discrepancies among the same type laser diodes. The near
      field performance focusses on the confinement effect of the VSAL aperture. A near
      field scanning optical microscopy is used to measure the near-field intensity
      distribution from a VSAL. The experimental results indicate that the near-field
      performance is affected by the aperture shape. A 100-nm C-aperture is proved to
      be superior to a 100 x 300 nm(2) rectangular aperture on both power throughput
      and peak intensity. These two apertures are fabricated on the same VSAL facet for
      the fairness of comparison. An optical spot beyond the diffraction limit is also
      obtained by fabricating a 70-nm C-aperture on a VSAL facet.

PMID- 18331502
TI  - Focussed ion beam machined cantilever aperture probes for near-field optical
      imaging.
AB  - Near-field optical probe is the key element of a near-field scanning optical
      microscopy (NSOM) system. The key innovation in the first two NSOM experiments
      (Pohl et al., 1984; Lewis et al., 1984) is the fabrications of a sub-wavelength
      optical aperture at the apex of a sharply pointed transparent probe tip with a
      thin metal coating. This paper discusses the routine use of focussed ion beam
      (FIB) to micro-machine NSOM aperture probes from the commercial silicon nitride
      cantilevered atomic force microscopy probes. Two FIB micro-machining approaches
      are used to form a nanoaperture of controllable size and shape at the apex of the
      tip. The FIB side slicing produces a silicon nitride aperture on the flat-end
      tips with controllable sizes varying from 120 nm to 30 nm. The FIB head-on
      drilling creates holes on the aluminium-coated tips with sizes down to 50 nm.
      Nanoapertures in C and bow tie shapes can also be patterned using the FIB head-on
      milling method to possibly enhance the optical transmission. A transmission
      collection NSOM system is constructed from a commercial atomic force microscopy
      to characterize the optical resolution of FIB-micro-machined aperture tips. The
      optical resolution of 78 nm is demonstrated by an aperture probe fabricated by
      FIB head-on drilling. Simultaneous topography imaging can also be realized using
      the same probe. By mapping the optical near-field from a bow-tie aperture,
      optical resolution as small as 59 nm is achieved by an aperture probe fabricated
      by the FIB side slicing method. Overall, high resolution and reliable optical
      imaging of routinely FIB-micro-machined aperture probes are demonstrated.

PMID- 18331503
TI  - Progress towards a thermally driven, infra-red near-field source using
      nanoheaters.

PMID- 18331504
TI  - Topological organization of NADPH-oxidase in haematopoietic stem cell membrane:
      preliminary study by fluorescence near-field optical microscopy.
AB  - The aim of this study was to characterize the local distribution and organization
      of the plasma membrane NADPH-oxidase (NOX) in human haematopoietic stem cell
      (HSC) by means of the fluorescence scanning near-field optical microscopy
      approach. The presence of NOX in haematopoietic stem cells is thought to have a
      functional role as O(2) sensor and/or as low-level reactive oxygen species (ROS)
      producer to be used as redox messenger for controlling cell growth and
      differentiation. Given the harmful potential of ROS, a fine-tuning of NOX
      activity is needed. The high resolution imaging of haematopoietic stem cell
      membrane obtained in this study combined with the immunodetection of NOX
      indicates for this the occurrence of a cluster-organized structure. These
      membrane 'rafts'-like micro-compartments may constitute localized protein
      aggregates whereby the assembly/activation of the NOX components are functionally
      integrated with upstream factors constituting signal-transduction platforms.

PMID- 18331505
TI  - A Poincare's approach for plasmonics: the plasmon localization.
AB  - A Poincare's approach is employed to characterize the excitation of a plasmon,
      which in essence corresponds to a zero of a complex S-matrix. Throughout this
      work we study the plasmonic behaviour of gold, as this metal not only is
      frequently used in experimental arrays, but also requires an accurate dispersion
      model to properly excite plasmons. We investigate the plasmonic behaviour of gold
      nanogratings by means of Born's approximation and the Finite-Elements Method.
      Also, a method based on the Poincare's approach is proposed to optimize this kind
      of structures.

PMID- 18331506
TI  - Cell wall investigations utilizing tip-enhanced Raman scattering.
AB  - Tip-enhanced Raman scattering is used to investigate the surface structure of the
      cell wall of Staphylococcus epidermidis with high lateral resolution and chemical
      specificity. For most biological samples, the transmission tip-enhanced Raman
      scattering set-up is ideally suited because it allows the specimen to be kept
      under specific environmental conditions, whereas it most efficiently collects the
      signal created at the field-enhancing probe. Special emphasis is given here to
      the parameters required to reproducibly set up the instrument, such that field
      enhancement factors can be estimated properly. Also the importance of control
      experiments to avoid misinterpretation of signals will be emphasized by an
      example.

PMID- 18331507
TI  - Fluorescent two-photon nanolithography.
AB  - Improving the excitation conditions in two-photon fluorescent lithography reduces
      the size of the fabricated structures to nanometre scales. We demonstrate that a
      precise control of the illumination profile and the scanning speed of the laser
      beam is enough to decrease the photo-polymerization volume of resins by orders of
      magnitude. This work also shows experimental evidence of surface effects that
      yield a different polymerization intensity threshold compared with bulk. Such
      phenomenon enables to perform a non-linear optical nanolithography in a simple
      way, allowing fast-prototyping procedures. We present a detailed study of the
      polymer growth process using fluorescence and atomic force microscopy.

PMID- 18331508
TI  - Characteristics of light intensity enhancement of a silver nanoprism with rounded
      corners.
AB  - We have fabricated silver nanoprisms of 100-600 nm side length by focussed ion
      beam lithography and measured the light intensity scattering spectra using dark
      field microscopy. Two resonance peaks due to localized surface plasmon excitation
      were observed in the spectra and their central frequency shown to depend on the
      prism size. The near-field electromagnetic intensity distribution with TE
      polarized light at the vacuum wavelength of 632.8 nm was measured. We have
      obtained a much lower light intensity enhancement than previously numerically
      predicated. However, scattering spectra obtained numerically, taking into account
      roundness of the prism corners, agree well with experimental ones. At the same
      time, the numerically determined field distribution was different to the near
      field intensity obtained experimentally. Our results suggest the particular shape
      of the corner region of the prism is a key factor for obtaining a large light
      intensity enhancement and shaping the local field distribution.

PMID- 18331509
TI  - Low-frequency electromagnetic field effects on functional groups in human skin
      keratinocytes cells revealed by IR-SNOM.
AB  - Human HaCaT cells, exposed for 24 h to a 1 mT (rms) 50 Hz sinusoidal magnetic
      field in a temperature-regulated solenoid, suffer detectable changes in their
      biochemical properties and shapes. By using infrared wavelength-selective
      scanning near-field optical microscopy, we observed changes in the distribution
      of the inner chemical functional groups and in the cell morphology with a
      resolution of 80-100 nm.

PMID- 18331510
TI  - Total internal reflection fluorescence microscopy study of spiral Ca2+ waves in
      single heart cell.
AB  - Spiral wave phenomena exist in many scales of nature and have attracted the
      attention of scientists from different fields. Although much work has been done
      on qualitative analysis of spiral waves, the mechanism of spiral waves'
      spontaneous formation and termination in living systems is still not clear. Here,
      by using total internal reflection fluorescence microscopy, we show the spiral
      waves of calcium signals in single rat cardiac myocytes and the simulation of the
      waves comprising calcium sparks. The mechanism of the formation and termination
      of spiral waves is attributable to the calcium release channels' refractory
      resulting from their stochastic release. We suggest that this mechanism can be
      adapted to other living systems.

PMID- 18331511
TI  - Study of the optical response of phase-change recording layer with zinc oxide
      nanostructured thin film.
AB  - Recently, use of nanostructured materials as a near-field optical active layer
      has attracted a lot of interest. The non-linear optical properties and strong
      enhancements of metallic oxide nanostructured thin films are key functions in
      applications of promising nanophotonics. For the importance of ultra-high density
      optical data storage, we continue investigating the ultra-high density recording
      property of near-field optical disk consisting of zinc oxide (ZnO(x))
      nanostructured thin film. A carrier-to-noise ratio above 38 dB at a recording
      mark size of 100 nm can be obtained in the ZnO(x) near-field optical disk by a
      DVD driver tester directly. In this article, we use an optical pump-probe system
      (static media tester) to measure the optical response of a phase-change recording
      layer (Ge(2)Sb(2)Te(5)) and demonstrate the high contrast of optical recording
      with a ZnO(x) nanostructured thin film in short pulse durations. Also, we
      investigate the dependence of writing power and the optical response in
      conventional re-writable recording layers and the phase-change material with
      ZnO(x) nanostructured thin film.

PMID- 18331512
TI  - Narrow plasmon mode in 2D arrays of silver nanoparticles self-assembled on thin
      silver films.
AB  - Extinction spectra of 2D arrays of silver nanoparticles self-assembled on 5-20-nm
      thick vacuum-deposited silver films exhibit extremely narrow plasmon mode in the
      blue spectral region, whereas the same particles self-assembled on thin films of
      Au, Cu, Cr and Ti damp the plasmon resonance. The observed narrowing was
      attributed to the plasmon coupling between the nanoparticles and between the
      nanoparticles and surface modes in the underlying silver film.

PMID- 18331513
TI  - Allergic Rhinitis and its Impact on Asthma (ARIA) 2008 update (in collaboration
      with the World Health Organization, GA(2)LEN and AllerGen).

PMID- 18331514
TI  - Feeding supplemental dried distiller's grains increases faecal shedding of
      Escherichia coli O157 in experimentally inoculated calves.
AB  - Escherichia coli O157 is an important foodborne pathogen and asymptomatic cattle
      serve as major reservoirs for human infection. We have shown a positive
      association between feeding distiller's grains and E. coli O157 prevalence in
      feedlot cattle. The objective of this study was to determine the effect of
      feeding dried distiller's grain (DDG) on faecal shedding of E. coli O157 in
      calves experimentally inoculated with E. coli O157. Holstein calves (five per
      treatment group), fed steam-flaked corn-based high-grain diets supplemented with
      0% (control) or 25% DDG, were orally inoculated with a five-strain mixture (6 x
      10(9) CFU/calf) of nalidixic acid-resistant (NalR) E. coli O157. Faecal samples
      were taken three times per week for 6 weeks to determine the prevalence and
      concentration of Nal E. coli O157. At the end of the study (day 43), calves were
      euthanized and necropsied. Ruminal, caecum, colon, and rectal contents, and
      rectoanal mucosal swab (RAMS) samples were collected at necropsy to determine
      NalR E. coli O157 concentration. There was a trend for an interaction between
      treatment and faecal sampling day. The concentration of NalR E. coli O157 in the
      faeces was significantly higher in faecal samples from calves fed DDG compared
      with control calves on days 35, 37, 39 and 42. At necropsy, the concentration of
      NalR E. coli O157 was higher in the caecum (P = 0.01), colon (P = 0.03) and
      rectum (P = 0.01) from calves fed DDG compared with control animals. The number
      of sites at necropsy positive for NalR E. coli O157 was higher in calves fed DDG
      compared with calves in the control treatment (P < 0.001). Our results indicate
      that E. coli O157 gut persistence and faecal prevalence increased in calves fed
      DDG, which potentially have important implications for food safety.

PMID- 18331515
TI  - Salmonella spp. in Bavarian liquid pig manure: occurrence and relevance for the
      distribution of antibiotic resistance.
AB  - In a representative study, 380 manure samples of pig farms distributed all over
      Bavaria (Germany) were screened for the presence of Salmonella spp. at the time
      of manure application to soil using methods adapted to DIN EN ISO 6579. The
      isolates were tested according to DIN 58940 for their susceptibility towards 26
      antimicrobial substances - such substances partly administered in animals, but
      mainly used in human therapy. Six out of 380 manure samples and, in addition, the
      only separated liquid manure sample examined, contained Salmonella isolates.
      Serotypes represented S. Typhimurium (n = 5), S. Derby (n = 1) and S. Infantis/S.
      Serogroup C1-(6,7:r:-)-form (each n = 1). Within the serovar S. Typhimurium, the
      most common phage type was DT104 (n = 3). All Salmonella isolates originated from
      'big' farms (>30/45 sows on combined/breeding farms or >220 fattening pigs). Four
      out of six manure samples contained resistant isolates; all resistant Salmonellae
      were multi-resistant. Two out of three DT104-isolates showed the typical penta
      resistance pattern often found in S. Typhimurium DT104, which was, furthermore,
      supplemented by other resistances. One Escherichia coli isolated together with a
      phage type DT104 S. Typhimurium also expressed the same penta-resistance pattern.

PMID- 18331516
TI  - Nationwide surveillance of salmonella in the faeces of pigs in Japan.
AB  - The prevalence of faecal carriage of salmonella in 5393 pigs reared on 218 pig
      farms located in 31 of 47 prefectures in Japan over the period July 2003 to June
      2005 was investigated. We isolated 172 strains belonging to 20 serovars and one
      untypable Salmonella enterica from 169 pig faecal samples (3.1%) collected from
      48 farms (22.0%). The most prevalent type of S. enterica was untypable O4,12:d:-
      which lacks phase 2 flagellar antigen, representing 29.1% (50/172) of all
      isolates. Of 26 S. enterica serovar Typhimurium isolates, 16 strains appeared to
      be definitive phage type 104 (DT104) by polymerase chain reaction.

PMID- 18331517
TI  - Evaluation of 65% permethrin spot-on and deltamethrin-impregnated collars for
      canine Leishmania infantum infection prevention.
AB  - During the 2004 and 2005 sand fly seasons, we evaluated the efficacy of a 65%
      spot-on solution of permethrin (Exspot, Schering & Plough) and deltamethrin
      impregnated collar (Scalibor, Intervet) in reducing Leishmania infantum
      infection, in a canine leishmaniasis (CanL) endemic region (Liguria) in Italy.
      Immunofluorescent assay (IFA) revealed that three of 120 dogs (2.5%) treated with
      a 65% spot-on solution of permethrin, as three of 119 dogs (2.5%) treated with
      deltamethrin-impregnated collar have shown seroconversion after sand fly season.
      On the contrary, seroconversion was 15% in 188 untreated control dogs. Treatment
      reduced the risk of infection by 84%. The difference in treated dogs and control
      ones is highly significant (chi2 = 12.4; P = 0.0004). Our results show that
      treatment with 65% spot-on solution of permethrin and the deltamethrin
      impregnated collar are effective in reducing the risk of acquiring L. infantum
      infection.

PMID- 18331518
TI  - American cutaneous leishmaniasis in horses from endemic areas in the north
      central mesoregion of Parana state, Brazil.
AB  - American cutaneous leishmaniasis (ACL) is an endemic disease in the north-west of
      Parana state, Brazil, where it occurs in humans and dogs. Few studies have been
      undertaken on the occurrence of the disease in other domestic animals and horses.
      In this study we investigated the infection of horses by Leishmania in ACL
      endemic rural areas. Direct agglutination test (DAT) and polymerase chain
      reaction (PCR) were employed. Fifty-five horses from rural areas in the
      municipalities of Doutor Camargo, Ourizona, Sao Jorge do Ivai, Ivatuba and Santa
      Fe (Agua do O) were analysed. DAT-detected antibody titres varied from 10 to 640,
      and 42 (76.3%) animals presented titres > or =20. PCR analyses led to the
      detection of Leishmania (Viannia) DNA in the blood samples of three (7.1%) of 42
      animals. The presence of anti-L. (V.) braziliensis antibodies and Leishmania
      (Viannia) DNA in horses from endemic areas suggests their participation in the
      ACL transmission cycle.

PMID- 18331519
TI  - Echinococcus granulosus infection in Spain.
AB  - Cystic echinococcosis (CE) caused by the cestode Echinococcus granulosus is an
      endemic disease in Spain. Although specific control programmes initiated in the
      1980s have led to marked reductions in CE infection rates in Spain, the disease
      still remains an important human and animal health problem in many regions of the
      country. Human incidence and livestock (including sheep, cattle, pigs and horses)
      prevalence data were gathered from national epidemiological surveillance
      information systems and regional institutions for the period 2000-2005.
      Additionally, data on the prevalence of E. granulosus infection in dogs were
      obtained from published literature. The most affected regions were those of the
      North Eastern, Central and Western parts of the country, (Autonomous Regions of
      Aragon, Castile-La Mancha, Castile-Leon, Extremadura, Navarre and La Rioja),
      where human CE incidence rates in the range of 1.1-3.4 cases per 10(5)
      inhabitants coexist with ovine/bovine CE prevalence rates up to 23%. Control
      programmes of hydatidosis/echinococcosis should be reinforced in these regions to
      reduce the prevalence of the disease.

PMID- 18331520
TI  - Prevalence of gastrointestinal bacterial pathogens in a population of zoo
      animals.
AB  - Faecal prevalence of gastrointestinal bacterial pathogens, including
      Campylobacter, Escherichia coli O157:H7, Salmonella, Shigella, Yersinia, as well
      as Arcobacter, were examined in 317 faecal specimens from 44 animal species in
      Belfast Zoological Gardens, during July-September 2006. Thermophilic
      campylobacters including Campylobacter jejuni, Campylobacter coli and
      Campylobacter lari, were the most frequently isolated pathogens, where members of
      this genus were isolated from 11 animal species (11 of 44; 25%). Yersinia spp.
      were isolated from seven animal species (seven of 44; 15.9%) and included,
      Yersinia enterocolitica (five of seven isolates; 71.4%) and one isolate each of
      Yersinia frederiksenii and Yersinia kristensenii. Only one isolate of Salmonella
      was obtained throughout the entire study, which was an isolate of Salmonella
      dublin (O 1,9,12: H g, p), originating from tiger faeces after enrichment. None
      of the animal species found in public contact areas of the zoo were positive for
      any gastrointestinal bacterial pathogens. Also, water from the lake in the centre
      of the grounds, was examined for the same bacterial pathogens and was found to
      contain C. jejuni. This study is the first report on the isolation of a number of
      important bacterial pathogens from a variety of novel host species, C. jejuni
      from the red kangaroo (Macropus rufus), C. lari from a maned wolf (Chrysocyon
      brachyurus), Y. kristensenii from a vicugna (Vicugna vicugna) and Y.
      enterocolitica from a maned wolf and red panda (Ailurus fulgens). In conclusion,
      this study demonstrated that the faeces of animals in public contact areas of the
      zoo were not positive for the bacterial gastrointestinal pathogens examined. This
      is reassuring for the public health of visitors, particularly children, who enjoy
      this educational and recreational resource.

PMID- 18331521
TI  - Serological survey for antibodies to Encephalitozoon cuniculi in pet rabbits in
      Italy.
AB  - Pet rabbits (n = 125) from Southern Italy were submitted to a serological
      screening for Encephalitozoon cuniculi, using an enzyme-linked immunosorbent
      assay (ELISA) and a carbon immunoassay (CIA). Seventy-eight examined rabbits
      showed clinical signs suggestive of encephalitozoonosis (head tilt, ataxia,
      paralysis, cataracts, uveitis, polyuria and polydipsia), whereas 47 were healthy
      rabbits. Antibodies anti-E. cuniculi were found in 84/125 (67.2%) sera analysed.
      The results of the chi-squared test showed that sex and health status had no
      significant effect (P > 0.05) on E. cuniculi seropositivity; however, rabbits
      older than 4 months had a seropositivity for E. cuniculi significantly (P < 0.05)
      higher than that of rabbits aged up to 4 months. The results of the present
      survey reinforce the assumption that rabbit may be indicated as the main
      reservoir of E. cuniculi; therefore, routine screening examinations in pet
      rabbits are strongly advised considering the zoonotic potential of this parasite.

PMID- 18331522
TI  - Identification of a novel HLA-DRB1 allele, DRB1*116502, by sequence-based typing
      in an African-American individual.
AB  - The novel allele HLA-DRB1*116502 differs from HLA-DRB1*110201 by nucleotide
      substitutions at codon 59 (GAG-->GAC) and 93 (CGG-->AGG).

PMID- 18331523
TI  - Identification of a novel HLA-A allele, HLA-A*9216.
AB  - The new human leukocyte antigen (HLA)-A*9216 differs from A*02010101 by a
      nonsynonymous nucleotide change at condon 76 (GTG>CTG).

PMID- 18331524
TI  - Identification of the novel HLA-A*240215 allele by haplotype-specific sequencing.
AB  - Here, we report on a novel allele human leukocyte antigen (HLA)-A*240215. This
      allele differs from HLA-A*240201 by a synonymous nucleotide exchange at
      nucleotide 255 in exon 2.

PMID- 18331525
TI  - Expanding diversity at the HLA-B locus: 28 novel HLA-B alleles.
AB  - Twenty-eight novel human leukocyte antigen-B alleles are described: one B*07
      (*0745), two B*08 (*0826 and *0831), one B*27 (*2731), four B*35 (*350106,
      *350402, *3566, and *3568), two B*37 (*370102 and *3711), two B*38 (*380102 and
      *3813), two B*39 (*3935 and *3939), one B*41 (*4108), one B*42 (*4209), two B*44
      (*4444 and *4448), two B*48 (*480302 and *4815), one B*51 (*5140), one B*55
      (*5523), one B*56 (*5617), two B*57 (*570103 and *5710), and three B*15 (*9505,
      *9510, and *9519). Sixteen of the variants are single-nucleotide substitutions
      from their most homologous allele, of which 10 result in amino acid changes
      (B*0745, *0831, *3813, *3935, *3939, *4815, *9505, *9509, *9510, and *9519) and 6
      are silent substitutions. The remaining alleles (B*0826, *2731, *3566, *3568,
      *3711, *4108, *4209, *4444, *4448, *5140, *5523, *5617, and *5710) differ from
      their most similar alleles by two to seven nucleotides substitutions, altering
      from one to five amino acids.

PMID- 18331526
TI  - A new HLA-B*08 allele, HLA-B*0828, found in two voluntary stem cell donors.
AB  - The novel allele HLA-B*0828 differs from HLA-B*080101 by three nucleotide
      exchanges at codon 113, 114, and 116 in exon 3.

PMID- 18331527
TI  - HLA-DQB1*0634, a novel DQB1 allele found by high-resolution HLA typing of a
      sibling pair for potential bone marrow transplantation.
AB  - In this paper, we characterize the novel human leukocyte antigen (HLA)-DQB1*0634
      allele we found in a sibling pair during high-resolution HLA typing in forecast
      of upcoming bone marrow transplantation. Both siblings, the female patient and
      her brother, were HLA identical, and therefore, both figured out the novel DQB1
      allele characterized by a nucleotide exchange 'C' to 'T' at position 565, which
      is the last nucleotide of DQB1 exon 3. DQB1 exon 4 sequencing confirmed the
      exchange of codon 189-arginine (CGG), which is replaced by tryptophan (TGG) in
      the new allele DQB1*0634.

PMID- 18331528
TI  - Expression of pemphigus-autoantigen desmoglein 1 in human thymus.
AB  - Desmoglein (Dsg) 1 is a transmembrane glycoprotein of the desmosome allowing cell
      cell adhesion between keratinocytes, whose expression is restricted to stratified
      squamous epithelia-like epidermis. Dsg1 is the target autoantigen of pathogenic
      autoantibodies produced by pemphigus foliaceus and 50% of pemphigus vulgaris
      patients in a Dsg1-specific T-cell-dependent pathway. Herewith, we show that mRNA
      of the DSG1 gene is present in normal human thymus and show by quantitative real
      time polymerase chain reaction analysis that the expression of DSG1 transcript
      increases with age. Although immunoblot analysis on human thymus extracts using
      different anti-Dsg1 antibodies did not allow to detect the protein, we show by
      double-immunofluorescence assay that Dsg1 is expressed at protein level by CD19+
      CD63+ cells located in the medulla. These data provide another illustration of
      the thymic expression of a tissue-specific autoantigen involved in an organ
      specific autoimmune disease, which may participate in the tolerance acquisition
      and/or regulation of Dsg1-specific T cells.

PMID- 18331529
TI  - Association of the HLA-G 14-bp insertion/deletion polymorphism with juvenile
      idiopathic arthritis and rheumatoid arthritis.
AB  - We tested the possible association of the 14-bp polymorphism of the HLA-G gene in
      the course of two inflammatory diseases, rheumatoid arthritis (RA) and juvenile
      idiopathic arthritis (JIA). Patients and controls were genotyped for the 14-bp
      polymorphism by polymerase chain reaction with specific primers for the exon 8 of
      the human leukocyte antigen (HLA)-G gene and the amplified fragment was
      visualized in a 6% polyacrylamide gel. A total of 106 JIA patients, 265 RA
      patients, 356 healthy adults and 85 healthy children were genotyped for the 14-bp
      polymorphism. Female JIA patients presented a higher frequency of the -14 bp
      allele when compared with female healthy children (0.743 and 0.500, corrected
      P=0.003), which reflected in the JIA group as a whole. This increased frequency
      of the -14-bp allele was observed in all JIA subtypes. In RA patients, no
      differences in allelic and genotypic frequencies were observed between patients
      and controls. No correlations were observed among genotype and disease severity
      or clinical manifestations. Our data suggest that the HLA-G -14 bp allele is
      probably a risk factor for JIA, mainly in females. Considering the differences
      observed in relation to gender, we suggest that hormonal differences can
      interfere with the development of JIA. Considering the RA patients, our data
      agree with results from the literature and highlight the differences in the
      etiology of RA and JIA.

PMID- 18331530
TI  - New HLA-A allele, A*0339, identified in a Spanish patient.
AB  - A novel human leukocyte antigen-A allele, officially named A*0339, was found in a
      patient when sequence-based typing was carried out for unrelated stem cell donor
      search. A*0339 differs from A*03010101 in a point mutation at codon 102 (GAC-
      >TAC), generating an exchange of amino acid from Asp to Tyr.

PMID- 18331531
TI  - Investigation of killer cell immunoglobulin-like receptor gene diversity in
      KIR3DL1 and KIR3DS1 in a transplant population.
AB  - Several overlapping amplicons were used to obtain the sequence of genomic DNA
      covering most of the coding regions of KIR3DL1 and KIR3DS1 from a family and 77
      bone marrow transplant patients and their unrelated donors. Alleles 3DL1*00101
      and *002 were most frequently observed in addition to 12 other known 3DL1
      alleles. A single 3DS1 allele, 3DS1*01301, was identified in the 31 of 32
      individuals carrying this gene. Two new alleles, 3DL1*01702 and 3DS1*058, were
      characterized. Three samples appeared to carry the duplicated killer cell
      immunoglobulin-like receptor (KIR) haplotype observed in other studies based on
      the presence of 3DS1 and two 3DL1 alleles. Additionally, one sample appeared to
      carry a novel KIR haplotype containing one 3DL1 and two 3DS1 alleles.

PMID- 18331532
TI  - Non-apoptotic functions of granzymes.
AB  - Granzymes (granule enzymes) are proteases released from cytotoxic lymphocyte
      granules into target cells to protect mammals from virus infection and
      transformed cells. Once released into the cytoplasm of the target cell, granzymes
      activate specific pathways to induce cell death. Although the induction of target
      cell death has been considered the central function for these proteases,
      accumulating evidence suggests that granzymes also possess additional non-death
      related functions. Thus, some granzymes can achieve direct antiviral activities
      through the cleavage of proteins encoded by viruses as well as host factors
      required for the viral life cycle. The presence of elevated concentrations of
      circulating granzymes in various inflammatory processes and granzyme-mediated
      cleavage of extracellular substrates suggest that these proteases may have
      extracellular effects relevant to virus and tumor rejection and the pathogenesis
      of chronic inflammatory diseases. Here, we discuss the current knowledge of the
      substrates and the proposed non-apoptotic functions of granzymes, with special
      interest in non-death-related functions of granzymes inside the target cell.

PMID- 18331533
TI  - Uptake of HIV and syphilis testing of pregnant women and their male partners in a
      programme for prevention of mother-to-child HIV transmission in Uganda.
AB  - OBJECTIVE: To describe uptake of HIV and syphilis testing in a prevention of
      mother-to-child HIV transmission programme in Uganda. METHODS: Analysis of data
      from routine HIV and syphilis testing at Entebbe Hospital antenatal services.
      RESULTS: A total of 20,738 women attended antenatal services. Exactly 62.8% of
      women, but only 1.8% of their male partners, accepted testing for HIV; 82.2% of
      women, but only 1.1% of their male partners accepted syphilis testing. Partners
      of women with positive HIV results were more likely to come for subsequent
      testing. Of 200 couples whose partners accepted HIV-testing within 30 days of one
      another, 19 (9.5%) were HIV-discordant, representing 65.5% of couples with at
      least one partner HIV-positive. HIV prevalence was 12.6% for women and 10.8% for
      men; syphilis prevalence was 4.0% for women and 6.2% for men. CONCLUSION: Uptake
      of HIV and syphilis testing was fairly good among pregnant women attending
      antenatal clinics at Entebbe Hospital, but very low among their male partners.
      The level of HIV-discordant couples was high. These clinics should be made more
      couples-friendly to identify both HIV-positive men for treatment and discordant
      couples for HIV prevention.

PMID- 18331534
TI  - Urban living and obesity: is it independent of its population and lifestyle
      characteristics?
AB  - OBJECTIVES: Living in an urban area influences obesity. However, little is known
      about whether this relationship is truly independent of, or merely mediated
      through, the demographic, socio-economic and lifestyle characteristics of urban
      populations. We aimed to identify and quantify the magnitude of this relationship
      in a Sri Lankan population. METHODS: Cross-sectional study of adults aged 20-64
      years representing the urban (n = 770) and rural (n = 630) populations, in the
      district of Colombo in 2004. Obesity was measured as a continuous variable using
      body mass index (BMI). Demographic, socio-economic and lifestyle factors were
      assessed. Gender-specific multivariable regression models were developed to
      quantify the independent effect of urban/ rural living and other variables on
      increased BMI. RESULTS: The BMI (mean; 95% confidence interval) differed
      significantly between urban (men: 23.3; 22.8-23.8; women: 24.2; 23.7-24.7) and
      rural (men: 22.3; 21.9-22.7; women: 23.2; 22.7-23.7) sectors (P < 0.01). The
      observed association remained stable independently of all other variables in the
      regression models among both men (coefficient = 0.64) and women (coefficient =
      0.95). These coefficients equated to 2.2 kg weight for the average man and 1.7 kg
      for the average woman. Other independent associations of BMI were with income
      (coefficient = 1.74), marital status (1.48), meal size (1.53) and religion (1.20)
      among men, and with age (0.87), marital status (2.25) and physical activity
      (0.96) among women. CONCLUSIONS: Urban living is associated with obesity
      independently of most other demographic, socio-economic and lifestyle
      characteristics of the population. Targeting urban populations may be useful for
      consideration when developing strategies to reduce the prevalence of obesity.

PMID- 18331535
TI  - Adherence to medical recommendations in pediatric transplant recipients: time for
      action.

PMID- 18331536
TI  - Decreases in circulating CD4+CD25hiFOXP3+ cells and increases in intragraft
      FOXP3+ cells accompany allograft rejection in pediatric liver allograft
      recipients.
AB  - We examined CD4(+)CD25(hi)FOXP3(+) cells Treg in children following liver
      transplantation and determined the relationship between Treg cell levels in the
      blood and in the graft. Peripheral blood was obtained from pediatric liver
      transplant patients at sequential time points: pre-transplant, one month, 3-4
      months, 6-7 months, and 11-12 months post-transplant. PBMC were isolated, labeled
      for CD4, CD25 and FOXP3 expression and analyzed by flow cytometry for
      CD4(+)CD25(hi)FOXP3(+) cells. Sorted CD4(+)CD25(hi) cells were assessed for
      functional activity. Pretransplant blood levels of CD4(+)CD25(hi)FOXP3(+) Treg
      cells were not significantly different from post-transplant blood levels of
      CD4(+)CD25(hi)FOXP3(+) Treg cells. However, the blood levels of
      CD4(+)CD25(hi)FOXP3(+) Treg cells were significantly decreased during acute
      rejection compared with levels when graft function was stable.
      Immunohistochemistry revealed that FOXP3(+) cells were increased in the portal
      region of livers with histopathologic evidence of acute graft rejection compared
      with livers without evidence of rejection and were localized primarily within the
      inflammatory infiltrate. These data indicate that Treg cells are found at the
      site of allograft rejection and may play a role in regulation of alloreactivity.
      Moreover, monitoring peripheral CD4(+)CD25(hi)FOXP3(+) Treg cell levels may be
      useful in improving the post-transplant management of pediatric liver allograft
      recipients.

PMID- 18331537
TI  - Focal ischemic necrosis in advanced biliary atresia cirrhosis.
AB  - This report correlates the clinical and biological findings, liver hemodynamics
      and histological features of focal INL in an infant with BA cirrhosis. An eight
      month old boy with BA, with previous successful porto-enterostomy, was admitted
      with signs of cholangitis and ascites. He was treated with antibiotics and
      diuretics with subsequent clinical improvement. Eight days later, while being fed
      with hyper-osmolar milk, he became febrile again: ASAT/ALAT climbed (9000/2300
      IU/L), liver function deteriorated. Infectious work-up was negative. Liver
      ultrasound showed reversed portal flow and a negative arterial diastolic flow.
      The patient recovered within five days under supportive treatment. A similar
      event recurred five days later. INL was suspected and semi-urgent living-related
      liver transplantation was performed, with uneventful post-operative course.
      Histology of the explanted liver showed extensive foci of INL of different ages.
      This report illustrates how the association of reversed portal and arterial
      diastolic flows, with subsequent liver hypoperfusion, may repeatedly cause foci
      of INL in BA cirrhosis, and lead to rapid progression to liver failure. Because
      of precarious hepatic blood supply in such patients, close monitoring of portal
      and diastolic arterial flows is recommended.

PMID- 18331538
TI  - Scurvy diagnosed in a pediatric liver transplant awaiting combined kidney and
      liver transplantation.

PMID- 18331539
TI  - Hematopoietic stem cell transplantation from a donor with Klinefelter syndrome
      for Wiskott-Aldrich syndrome.
AB  - WAS is a rare X-linked recessive disorder characterized by primary progressive T
      cell immunodeficiency, impaired antipolysaccharide antibody response,
      thrombocytopenia with small platelet, and eczematoid dermatitis. Untreated
      patients with typical WAS have poor prognosis with the major causes of death
      being infection, bleeding, lymphoproliferative disorders, and malignancy. Due to
      the increased risk of infectious and hemorrhagic episodes the best results with
      HSCT are achieved in patients less than five yr of age and are recommended as
      early as possible. Here, we report a three-yr-old boy with WAS who underwent UCB
      and BMT from his genotypically identical brother with Klinefelter syndrome.

PMID- 18331540
TI  - Lipoprotein profile changes in children after renal transplantation in the modern
      immunosuppression era.
AB  - There are little data on prevalence of dyslipidemia in pediatric kidney TX
      recipients in the modern IS era. LP profiles of 38 TX recipients receiving triple
      IS with MMF, prednisone, and tacrolimus were compared with those of 11 children
      on HD using mixed model multiple linear regression analysis of repeated measures
      after adjusting for age, sex, ethnicity, duration of ESRD, and BMI. TC and LDL
      levels were significantly higher in TX compared with HD, whereas there was no
      difference in the HDL, VLDL, and TG levels. TC and LDL in TX children had no
      association with age, sex, ethnicity, and duration of ESRD, stage of chronic
      kidney disease, DM, BMI percentile, and gain in percentage IBW. Five children
      treated with atrovastatin had a significant reduction in TC, LDL, VLDL, and TG at
      3-6 months post-treatment compared with pretreatment levels, whereas there was no
      difference in HDL or tacrolimus levels after treatment. No side effects of
      therapy were observed. Although dyslipidemia remains a significant problem in
      pediatric renal TX recipients in the modern era, the prevalence may have
      decreased with use of newer IS drugs.

PMID- 18331541
TI  - Clinical significance of peripheral blood Epstein-Barr viral load monitoring
      using polymerase chain reaction in renal transplant recipients.
AB  - PTLD is a complication of EBV infection. We examined the efficacy of EBV-PCR
      monitoring to detect early replication in an attempt to prevent EBV-associated
      PTLD. Blood EBV levels in 156 renal transplant recipients (58 children) from
      three institutions over nine yr were retrospectively analyzed. Patients who were
      asymptomatic and at high risk for PTLD were monitored for EBV infection by PCR or
      serology followed by PCR at the time of EBV seropositivity. More children than
      adults had positive EBV-PCR (12/58 vs. 2/98, p < 0.001). Adults remained
      asymptomatic and viremia resolved post-therapy. 3/12 EBV-PCR positive children
      developed PTLD (3/12 children vs. 0/2 adults, p = NS). Two out of three with PTLD
      were initially monitored by serology, and later by PCR. PTLD resolved post
      therapy in all three patients. The remaining 9/12 EBV-PCR positive children
      stayed asymptomatic. None of the children and adults with negative EBV-PCR
      developed PTLD. EBV-PCR monitoring in high-risk renal transplant recipients,
      especially in children, may allow early diagnosis and intervention, and therefore
      may help in preventing EBV-associated PTLD.

PMID- 18331542
TI  - Potential immunosuppressive effects of statins.

PMID- 18331544
TI  - Acquired renal cysts after pediatric liver transplantation: association with
      cyclosporine and renal dysfunction.
AB  - ACKD has been observed in children on dialysis and with chronic renal
      insufficiency. In one report, ACKD was observed in 30% of pediatric liver
      transplant recipients after 10 yr. We retrospectively reviewed all renal imaging
      and measurements of GFR of 235 childhood liver transplant recipients with no
      known risk for renal cyst formation, no evidence of renal cyst(s) at the time of
      transplantation and renal imaging at least one yr post-transplant. Twenty-six
      patients (11%) developed one or more cyst(s). Mean GFR was significantly lower in
      patients with renal cyst(s). Two (1.4%) of the 146 patients treated with
      tacrolimus and 24 (27%) of the 89 patients treated with CsA acquired renal
      cyst(s) (p < 0.001). CsA-treated patients had significantly lower GFR.
      Multivariate analysis identified CsA as the only independent variable associated
      with ACKD. These results confirm that ACKD can be a late complication of
      pediatric liver transplantation. Those at most risk are at least 10-yr post-liver
      transplantation, have been treated with CsA and have impaired renal function. We
      speculate that ACKD in these patients is the result of calcineurin inhibitor
      nephrotoxicity. Whether patients with ACKD will be prone to develop solid renal
      tumors is unknown.

PMID- 18331545
TI  - Scurvy diagnosed in a pediatric liver transplant patient awaiting combined kidney
      and liver retransplantation.
AB  - First described in the 1500 s, scurvy is infrequently seen in industrialized
      countries today, although vulnerable patient groups remain. A 15-yr-old girl
      underwent liver transplantation at age 26 months for a primary diagnosis of
      biliary hypoplasia, and subsequently developed late allograft failure and
      progressive renal insufficiency culminating in listing for combined liver
      retransplantation and kidney transplantation at age 13 yr. She required regular
      hemodialysis treatment for 12 months prior to deceased donor organ availability,
      with a complicated clinical course including recurrent septic episodes and severe
      cachexia. Ten months after initiation of hemodialysis, she presented with severe
      bone pain, purpura, ecchymoses, gingival hyperplasia, mucosal bleeding, and
      subconjunctival hemorrhages. Serial serum ascorbic acid levels were found to be
      extremely low (<10 micromol/L) despite routine supplementation both in her
      dialysate and via regular oral supplementation. Histopathology from skin biopsy
      revealed purpura, hyper- and parakeratosis, and follicular plugging. She had ECG
      and 2D echocardiogram disturbances, as well as osteopenia and sclerosis of the
      extremities on radiological evaluations. Therapy with high-dose ascorbic acid (1
      g/day orally) led to complete resolution of skin lesions. This case highlights
      the importance of awareness and recognition of this historic diagnosis, and
      particularly in children with end-stage organ disease with severely compromised
      nutrition.

PMID- 18331546
TI  - Melatonin usage in ulcerative colitis: a case report.

PMID- 18331547
TI  - What is the association between the tumor necrosis factor-alpha inhibitor
      infliximab and complex regional pain syndrome type I?

PMID- 18331548
TI  - Accidental cannulation of an aberrant radial artery.

PMID- 18331549
TI  - Anesthesia for orthopedic surgery in Pallister-Killian syndrome.

PMID- 18331550
TI  - Severe hypertension and bradycardia after dexmedetomidine for radiology sedation
      in a patient with acute transverse myelitis.

PMID- 18331551
TI  - Lessons from transporting newborn infants with known or suspected congenital
      heart disease.

PMID- 18331552
TI  - Brachial plexus block for the child with Kartagener's syndrome.

PMID- 18331553
TI  - Scurvy: a disease of anesthetic interest? Scurvy and anesthesia.

PMID- 18331554
TI  - Effects of blood sample volume on hematocrit in critically ill children and
      neonates.
AB  - BACKGROUND: There are no studies correlating the volume of blood taken from
      children and hematocrit (Hct) stability, relating those changes to duration of
      stay, severity of illness or weight. Earlier studies in neonates suggest that
      repeated sampling results in a drop in Hct. AIM: To characterize the changes in
      Hct in children of all ages admitted to intensive care over a 5-day period
      following routine blood volume sampling. METHODS: We undertook an open
      prospective observational study. Eligible children were recruited sequentially
      and data recorded for 5 days following admission. The bedside nurse recorded the
      daily volume of blood samples taken and transfusions given. Daily Hct was noted
      from the routine full blood count. The relationship between changes in Hct and
      blood sample volume and transfusion requirement was studied. RESULTS: There were
      no differences in mean Hct on admission at end of the study (P = 0.69, n = 30)
      nor in the median blood volume sampled between transfused and nontransfused
      groups (7.5 ml.kg(-1) vs 7.9 ml.kg(-1), P = 0.88). The largest blood sample
      volumes were taken on admission and from the smallest patients. CONCLUSION: We
      have quantitated the change in Hct and size of blood volume taken for routine
      laboratory studies. We suggest that children can tolerate 0.25 ml.kg(-1).day(-1)
      blood sampling without a fall in Hct and sampling can be tailored to the
      individual child according to the admission Hct.

PMID- 18331555
TI  - Study of the adhesiveness of medical tapes when wet, dry or following application
      of Friars' balsam.
AB  - BACKGROUND: Adhesive tapes are routinely used during anesthesia for vital roles
      such as securing tracheal tubes or intravascular access devices. There are
      currently very few experimental data available to guide the choice of tape for a
      particular indication. METHODS: The performance of four medical adhesive tapes
      (Sleek, Elastoplast, Mefix and Leukoplast zinc oxide) was evaluated under three
      different conditions (wet, dry and following prior application of Friars'
      balsam). A strain gauge was used to determine the force required to detach each
      tape from the skin of the inner forearm. The test was repeated 20 times under
      each standardized condition. Statistical analysis was performed using two way
      anova and the Scheffe posthoc test. RESULTS: Leukoplast was the most adhesive
      tape overall (P < 0.001); Sleek was more adhesive than Mefix and Elastoplast (P <
      0.001); and Mefix was more adhesive than Elastoplast (P = 0.018). Under wet
      conditions, Elastoplast and Mefix were less adhesive than when dry (P < 0.001),
      whereas the adhesiveness of Sleek and zinc oxide was unchanged. Friars' balsam
      significantly increased the adhesiveness of Elastoplast and Sleek (P = 0.02 for
      both). CONCLUSIONS: There is a dramatic variation in performance between
      different adhesive tapes and between different conditions, which has implications
      for the choice of tape for a particular clinical application.

PMID- 18331556
TI  - Morphology of the sella turcica in Axenfeld-Rieger syndrome with PITX2 mutation.
AB  - BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder
      with an incidence of 1:200 000. Genotype and phenotype are heterogeneous and
      clinical morphology impresses with variable expressivity. Additionally to the
      typical craniofacial and dental aberrations anomalies in the morphology of sella
      turcica are discussed. METHOD: In a multidisciplinary genetic and clinical study
      four patients of a family with ARS were screened by direct DNA sequencing.
      Radiographic analysis of the patients was performed for evaluating cranial and
      dental structures. Additionally, a specific analysis of the morphology of the
      sella turcica was made on the radiographs. RESULTS: Screening for PITX2 and FOXC1
      mutations revealed a P64L missense mutation in PITX2 in all four patients. The
      cephalometric analysis showed a midface hypoplasia associated with a skeletal
      Class III. All patients showed a sella turcica bridge combined with a prominent
      posterior clinoid process followed by a steep clivus and an elongated sella
      turcica. CONCLUSION: The incidence of a sella turcica bridge in combination with
      a PITX2 mutation would suspect that sella turcica anomalies are typical symptoms
      of the syndrome. Sella turcica anomalies in association with craniofacial and
      dental aberrations, such as maxillary retrognathia, skeletal Class III
      relationship and hypoplasia of teeth, might be important indicators for ARS
      caused by PITX2 mutation.

PMID- 18331557
TI  - Expression of phosphorylated Akt in oral carcinogenesis and its induction by
      nicotine and alkaline stimulation.
AB  - BACKGROUND: In Taiwan, it is well documented that cigarette smoking and areca nut
      chewing contribute to the risk of oral squamous cell carcinoma (OSCC). The role
      of phosphorylated Akt (p-Akt) in oral carcinogenesis induced by nicotine and
      alkaline environments was investigated. METHOD: Immunohistochemistry (IHC) was
      used to detect p-Akt expression in cancerous (n = 30) precancerous (n = 30), and
      normal mucosa tissues (n = 10). Western blotting was used to detect time
      dependent induction of p-Akt by 100 microM nicotine in normal human bronchial
      epithelial cell (NHBE), normal human oral keratinocytes (NHOK), immortalized
      human epithelial cells (HaCaT) and OEC-M1 cells, dose-dependent induction of p
      Akt in OEC-M1 and HaCaT cells and pH effect of p-Akt in OEC-M1. The unpaired t
      test and the Fisher's exact test were used to analyze the p-Akt immunoreactivity
      in various groups and its association with clinicopathological parameters.
      RESULTS: Higher p-Akt expression in cancerous group than in normal mucosa (P =
      0.0002) and precancerous (P = 0.0049) groups was observed. A time-dependent
      increase in p-Akt in the NHBE, NHOK, HaCaT and OEC-M1 cell lines was observed
      with 100 microM nicotine treatment. The dose-dependent increase in p-Akt by
      nicotine treatment in HaCaT and OEC-M1 cells was obviously observed. Higher p-Akt
      expression in more alkaline environment (pH 8.0) was observed than at pH 7.4 in
      OEC-M1 cells. CONCLUSION: A potential role for increased p-Akt may relate to the
      dose and time of nicotine use. The potential role of an alkaline environment to
      enhance nicotine-related oral carcinogenesis may exist.

PMID- 18331558
TI  - Clinical and pathologic manifestation of oesophagostomosis in African great apes:
      does self-medication in wild apes influence disease progression?
AB  - Nodular worms (Oesophagostomum spp.) are common intestinal parasites found in
      cattle, pig, and primates including humans. In human, they are responsible for
      serious clinical disease called oesophagostomosis resulting from the formation of
      granulomas, caseous lesions or abscesses in intestinal walls. In wild great apes,
      the fecal prevalence of this parasite is high, but little information is
      available concerning the clinical signs and lesions associated. In the present
      study, we describe six cases of multinodular oesophagostomosis in free-ranging
      and ex-captive chimpanzees and captive gorillas caused by Oesophagostomum
      stephanostomum. While severe clinical signs associated with this infection were
      observed in great apes raised in sanctuaries, nodules found in wild chimpanzees
      do not seem to affect their health status. One hypothesis to explain this
      difference would be that in wild chimpanzees, access to natural environment and
      behavior such as rough leaves swallowing combined with ingestion of plants having
      pharmacological properties would prevent severe infection and decrease potential
      symptoms.

PMID- 18331559
TI  - Risk factors associated with surgical site infection and the development of short
      term complications in macaques undergoing indwelling vascular access port
      placement.
AB  - BACKGROUND: Risk factors associated with surgical site infection (SSI) and the
      development of short-term complications in macaques undergoing vascular access
      port (VAP) placement are evaluated in this study. METHODS: Records from 80
      macaques with VAPs were retrospectively reviewed. Logistic regression was used to
      identify factors associated with short-term post-operative complications.
      RESULTS: The primary outcome was SSI, which occurred in 21.6% (52.6% in the first
      12 months vs. 13% thereafter) of procedures. SSI was associated with major
      secondary complications including VAP removal (11.4%), wound dehiscence (5.7%),
      and mechanical catheter occlusion (5.7%). In multivariate modeling, only surgical
      program progress was a statistically significant predictor of SSI, while animal
      compliance had a slightly protective effect. CONCLUSIONS: Vascular access ports
      have a moderate risk of complications, provided the surgical program optimizes
      best practices. Under complex experimental conditions, VAPs represent an
      important refinement, both improving animals' overall well-being and environment
      and reducing stress.

PMID- 18331560
TI  - Persistence of challenging behaviours in adults with intellectual disability over
      a period of 11 years.
AB  - BACKGROUND: Challenging behaviours in people with an intellectual disability (ID)
      often develop early and tend to persist throughout life. This study presents data
      on the chronicity of challenging behaviours in adults with ID over a period of 11
      years, and explores the characteristics of people with persistent serious
      behaviour problems. METHOD: Support staff provided data on 58 adults living in a
      long-term residential facility using an interview survey schedule assessing
      challenging behaviours in 1992 and 2003. RESULTS: Participants presenting with
      serious physical attacks, self-injury and frequent stereotypy were the most
      likely to persist in these behaviours over time. These behaviours were
      characterised by high persistence percentages and associations over time.
      However, the earlier presence of serious challenging behaviours did not
      significantly affect the likelihood of serious challenging behaviours in 2003.
      Individuals with persisting behaviour problems differed from those who did not
      present serious behaviour problems on the basis of their younger age, increased
      mobility, and decreased sociability and daily living skills in 1992. CONCLUSIONS:
      Estimates of persistence for challenging behaviours are affected by the
      statistics chosen to represent stability. The apparent persistence of serious
      challenging behaviours highlights the need to identify the factors related to
      maintenance of these behaviours over time. The participant characteristics and
      adaptive behaviours identified in the present study were not consistently related
      to the persistence of challenging behaviours. Therefore, other factors, including
      environmental characteristics, are likely to be related to challenging behaviour
      persistence.

PMID- 18331561
TI  - Integrated specialty service readiness in health reform: connections in
      haemophilia comprehensive care.
AB  - The World Health Organization (WHO) has identified primary healthcare reform as a
      global priority whereby innovative practice changes are directed at improving
      health. This transformation to health reform in haemophilia service requires
      clarification of comprehensive care to reflect the WHO definition of health and
      key elements of primary healthcare reform. While comprehensive care supports
      effective healthcare delivery, comprehensive care must also be regarded beyond
      immediate patient management to reflect the broader system purpose in the care
      continuum with institutions, community agencies and government. Furthermore,
      health reform may be facilitated through integrated service delivery (ISD). ISD
      in specialty haemophilia care has the potential to reduce repetition of
      assessments, enhance care plan communication between providers and families,
      provide 24-h access to care, improve information availability regarding care
      quality and outcomes, consolidate access for multiple healthcare encounters and
      facilitate family self-efficacy and autonomy [1]. Three core aspects of ISD have
      been distinguished: clinical integration, information management and technology
      and vertical integration in local communities [2]. Selected examples taken from
      Canadian haemophilia comprehensive care illustrate how practice innovations are
      bridged with a broader system level approach and may support initiatives in other
      contexts. These innovations are thought to indicate readiness regarding ISD.
      Reflecting on the existing capacity of haemophilia comprehensive care teams will
      assist providers to connect and direct their existing strengths towards ISD and
      health reform.

PMID- 18331562
TI  - Haematological changes after switching from stavudine to zidovudine in HIV
      infected children receiving highly active antiretroviral therapy.
AB  - OBJECTIVE: In resource-limited countries, stavudine (d4T) is commonly used as
      part of the initial highly active antiretroviral therapy (HAART) regimen. Many
      patients who subsequently develop lipodystrophy switch from d4T to zidovudine
      (ZDV), a drug that can be myelotoxic. We aimed to study the spectrum and severity
      of haematological changes following this substitution. METHODS: This was a
      retrospective cohort study. The inclusion criteria were as follows: HIV-infected
      children were included who (1) were 2-15 years old at the time of HAART
      initiation, (2) had not been diagnosed as having haematological diseases, (3) had
      been receiving a first HAART regimen consisting of either nevirapine or
      efavirenz, together with lamivudine and d4T, for at least 48 weeks and (4) had
      switched from d4T to ZDV at least 48 weeks previously. RESULTS: Seventy-eight
      children were included in the study. Thirty-six (46%) were male. The mean age was
      10.3 years (standard deviation 3.1 years). The switch had been made a median time
      of 65 weeks (range 48-97 weeks) previously. There was no significant change in
      CD4 lymphocyte count or percentage, or HIV RNA level, after the switch. There was
      a statistically significant decrease in haemoglobin level (12.6 vs.12.1 g/dL;
      P<0.001), total white blood cell (WBC) count (8088 vs. 6910 cells/microL;
      P<0.001) and absolute neutrophil count (ANC) (4320 vs. 3448 cells/microL;
      P<0.001). However, the decreases never reached Division of AIDS grade 3 or 4
      severity, and none of the patients had clinical symptoms or signs of anaemia,
      leukopenia, or neutropenia. No participant had to discontinue ZDV during the 48
      week follow-up period. CONCLUSION: In a paediatric population, statistically
      significant decreases in haemoglobin level, WBC count and ANC occurred following
      the substitution of d4T with ZDV, but the magnitudes of the decreases were small
      and not clinically significant.

PMID- 18331563
TI  - Presentation, diagnosis and management of tuberculosis in HIV-infected children
      in the UK.
AB  - OBJECTIVES: Management of HIV-infected children with tuberculosis (TB) is
      challenging. The objective of this study was to assess current treatment and
      outcomes in a resource-rich setting in the era of highly active antiretroviral
      therapy (HAART). METHODS: A retrospective case-note review of coinfected children
      was carried out in a large UK-based HIV family clinic. RESULTS: Of 328 HIV
      infected children, 18 were diagnosed and treated for active TB. TB presentation
      led to HIV diagnosis in eight of these 18 children. TB was confirmed
      microbiologically in 33% of children. Fifteen of the 18 children presented with
      pulmonary TB, and three with extrapulmonary TB (EPTB). Immunological status at TB
      diagnosis did not predict EPTB. The mean CD4 T-cell count at TB presentation was
      402 cells/microL (mean CD4 percentage 16%), with a range of 0-790 cells/microL (0
      34%). In seven children concurrently treated with HAART and anti-tuberculous
      therapy (ATT), therapeutic drug monitoring (TDM) guided management. No immune
      reconstitution disease occurred. There was one death, unrelated to TB, 2 years
      after completion of ATT. CONCLUSIONS: An HIV test should be considered in all
      children diagnosed with TB, especially if there are epidemiological risk factors.
      Our experience shows that, even with deferral of HAART in concurrently infected
      children, good therapeutic responses to ATT can be achieved. Where necessary, TDM
      guiding concurrent HAART and ATT can facilitate good clinical and virological
      responses.

PMID- 18331564
TI  - Lopinavir/ritonavir monotherapy as maintenance treatment in HIV-infected
      individuals with virological suppression: results from a pilot study in Brazil.
AB  - OBJECTIVE: The aim of the study was to evaluate the possibility of using
      lopinavir/ritonavir (LPV/RTV) alone as maintenance therapy in HIV-infected
      individuals with virological suppression. DESIGN: This was a single-armed single
      centre pilot trial. METHODS: Asymptomatic HIV-infected patients on highly active
      antiretroviral therapy (HAART) including LPV/RTV, and with plasma HIV RNA <40
      copies/mL for at least 6 months, were enrolled in the study, during which they
      continued with LPV/RTV alone. The intention was to recruit 25 patients to be
      followed for 2 years. Viral failure was defined as two consecutive HIV RNA
      measurements >40 copies/mL. Nadir and baseline CD4 cell counts, highest ever HIV
      RNA load, time with undetectable viraemia before monotherapy, number of previous
      antiretroviral (ARV) regimens, and gene polymorphism at CYP3A4 and CYP3A5 were
      evaluated. RESULTS: All patients (27) completed the study. Their median age was
      43 years, and 66% were men. Ten patients (37%) failed to maintain virological
      suppression (the median time to HIV rebound was 10.5 months, with a range of 4-23
      months). One patient developed full resistance to LPV and another developed
      neurocognitive impairment while on LPV/RTV which improved after HAART
      reintroduction. There were no differences between failures and nonfailures
      according to the analysed parameters. Patients with viral failure were
      successfully resuppressed. CONCLUSIONS: LPV/RTV maintenance therapy was
      associated with 37% failure, a higher than expected failure rate. In order to
      ensure that unnecessary risks are not being taken in patients on LPV/RTV, this
      finding should be further evaluated in large randomized trials for longer periods
      of follow-up.

PMID- 18331565
TI  - The relationships between oral status, physical and mental health, nutritional
      status and diet type in elderly Japanese women with dementia.
AB  - OBJECTIVES: To suggest methods for maintaining an adequate nutritional status for
      elderly patients with dementia by evaluating the relationships between oral
      status, physical and mental health, and feeding conditions. BACKGROUND: Feeding
      difficulties in dementia patients are related to food intake, and failure to eat
      may be associated with weight loss in long-term care facilities. The relationship
      between compromised oral function and diet is still unclear. MATERIALS AND
      METHODS: A cross-sectional study of 94 elderly women with dementia (mean age 89.6
      +/- 5.6 years) from a nursing home was undertaken to investigate their oral,
      physical and mental and nutritional status. RESULTS: There were significant
      differences in serum albumin (p = 0.0284), N-ADL (p = 0.0005), NM scale (p =
      0.0004) and HDS-R (p = 0.0004) between denture wearers and non-denture wearers.
      However, there were no significant differences in body mass index between denture
      wearers and non-denture wearers. CONCLUSION: A suitable type of diet and
      assistance with feeding could maintain the nutritional status of elderly patients
      with dementia if they are still feeding themselves. The nutritional support team
      will benefit from the participation of a dentist.

PMID- 18331566
TI  - Mitosis in dermatofibroma: a worrisome histopathologic sign that does not
      necessarily equal recurrence.
AB  - BACKGROUND: High mitotic rate is a worrying histopathologic feature that
      pathologists occasionally face when diagnosing benign fibrous histiocytoma (BFH),
      that otherwise seem to be benign. The clinical significance of this histologic
      feature has not been completely studied, because no studies on large series of
      BFH have been carried out, concerning mitotic rate as the only worrisome
      morphologic sign, in relation with recurrence. METHODS: In order to study how
      common a high mitotic rate is in BFH, which do not present any other worrisome
      morphological signs, we studied 200 cases from our archives and counted the
      number of mitosis per 10 high power fields (HPFs) in all of them. We selected
      those cases that had a mitotic number of 4 or more mitosis per 10 HPF. We also
      performed the immunohistochemical study with MIB-1 antibody (DakoCytomation,
      Denmark A/S). The clinical histories of the patients were also reviewed, in order
      to find out if there had been any recurrence. RESULTS: Four BFH presented four or
      more mitosis in ten HPF. None of them had presented any recurrence or metastasis,
      and the follow-up time was at least for 71 months. CONCLUSIONS: We conclude that
      common BFH can occasionally present a high mitotic rate and still show a benign
      behavior.

PMID- 18331567
TI  - CD34-positive dendritic cells disappear from scars but are increased in
      pericicatricial tissue.
AB  - CD34-positive stromal cells (CD34SC) are distributed throughout the body,
      including the dermis. They are thought to play a role in maturation and
      proliferation of adjacent mesenchymal and epithelial stem cells and in immune
      responses. To investigate the role of such cells in wound healing after excision
      of cutaneous lesions, we examined the distribution and quantity of CD34SC in
      scars from the sites of removal of malignant skin tumors and from reconstructive
      surgery, as well as in samples of normal skin. In normal skin, CD34 staining was
      confined to dendritic cells in the dermis, endothelial cells, perifollicular
      cells and eccrine glands. In cutaneous scars, the cicatricial tissue was totally
      devoid of CD34SC. However, the dermis adjacent to scar showed increased numbers
      of CD34SC as compared with normal skin [41.5 cells/mm(2) vs. 24.5 cells/mm(2) (p
      < 0.001)]. We conclude that CD34SC disappears from scars but are induced to
      proliferate in pericicatricial tissue. The cells in question may play a role in
      remodeling of scarred skin. One should be aware that augmented labeling for
      CD34SC around scars is common; it should not be interpreted as evidence for the
      persistence or recurrence of tumors that may also express CD34.

PMID- 18331568
TI  - Involvement of granzyme B and granulysin in the cytotoxic response in lichen
      planus.
AB  - BACKGROUND: Lichen planus is an inflammatory dermatosis involving either skin
      and/or mucosal epithelial surfaces. A cell-mediated cytotoxicity response is the
      main suspected mechanism of this dermatosis. Granzyme B and granulysin are
      components of the cytoplasmic granules of cytotoxic T lymphocytes and natural
      killers. They are involved in cell-mediated apoptosis. This work studies the
      possible implication of granzyme B and granulysin in the cell-mediated
      cytotoxicity response in lichen planus. METHODS: In situ expression of granzyme B
      and granulysin was studied by real-time reverse transcriptase polymerase chain
      reaction in 15 biopsies of lichen planus. The distribution and the phenotype of
      the inflammatory infiltrate and the expression of granzyme B were studied by
      immunohistochemistry in seven other biopsies of lichen planus. RESULTS: Granzyme
      B and granulysin mRNA expression was one to two hundred times greater than in
      biopsies of normal skin. Immunohistochemical study revealed that the
      lymphohistiocytic infiltrate consisted mainly of CD4+ and CD8+ lymphocytes.
      Granzyme B+ cells were observed close to apoptotic keratinocytes. CONCLUSION: Our
      results suggest a central role for cell-mediated cytotoxicity by the granule
      exocytosis pathway probably because of auto-cytotoxic T-cell clones in the
      pathogenesis of lichen planus.

PMID- 18331569
TI  - GMS is superior to PAS for diagnosis of onychomycosis.
AB  - BACKGROUND: Onychomycosis is a common cause of deformed nails. Periodic acid
      Schiff (PAS) stains are more sensitive than fungal cultures for diagnosing
      onychomycosis. We performed a retrospective study comparing the use of PAS and
      Gomori methenamine silver (GMS) stains for histopathologic diagnosis of
      onychomycosis. METHODS: GMS stains were performed on 20 PAS-positive and 51 PAS
      negative cases from nail biopsies with a clinical diagnosis of onychomycosis. The
      PAS stained slides and GMS stained slides were evaluated for the presence of
      fungal hyphae. The results were analyzed with McNemar's test. RESULTS: All 20 PAS
      positive cases were also positive with GMS stains. Of the 51 PAS-negative cases,
      GMS stains detected an additional five cases with fungal hyphae. GMS stains were
      quantitatively superior (p < 0.0253). GMS stains were also qualitatively
      superior. More fungal hyphae were highlighted and fungal hyphae were more easily
      recognized on low or medium power magnification. CONCLUSIONS: GMS stains are
      superior to PAS stains for the routine diagnosis of onychomycosis.

PMID- 18331570
TI  - The histological and pathogenetic spectrum of cutaneous disease in monoclonal
      gammopathies.
AB  - The dermatological disorders associated with monoclonal gammopathies are
      clinically heterogeneous and may be divided into four groups with distinctive
      pathogenetic mechanisms (a) specific (infiltrative) disorders including primary
      and secondary cutaneous plasmacytoma and cutaneous lymphoplasmacytic infiltration
      of Waldenstrom's disease (b) skin disorders because of the deposition of
      monoclonal immunoglobulin (M protein), including amyloidoisis macroglobulinemia
      cutis, light chain deposition of Randall's disease, follicular spicules of the
      nose, and cryoglobulinemia (c) skin disorders associated with monoclonal
      gammopathies, including highly associated (>50%), weakly associated (<50%) or
      anecdotal and (d) miscellaneous (non specific). In most cases, histopathology is
      crucial to confirm or to diagnose those skin conditions and is also very useful
      to understand their pathogenetic mechanisms.

PMID- 18331571
TI  - Synchronous onset of multiple cutaneous neuroendocrine (Merkel cell) carcinomas
      localized to the scalp.
AB  - Merkel cell carcinoma (MCC) is a rare aggressive neoplasm that typically presents
      as a solitary nodule or plaque on sun-exposed skin of the elderly. Although
      multiple MCC have been described, they are rare, and metastases must be excluded.
      We report a case of a 59-year-old white male who presented with abrupt onset of
      multiple small bluish papules on his frontal scalp. On low power, the tumor had
      the overall histological silhouette of a nodular basal cell carcinoma. However,
      because of the lack of an epithelial connection and the cell's cytomorphological
      features, a MCC was considered and was subsequently confirmed using
      immunohistochemical stains. The MCC described in this report is unusual in that
      it presented as multiple cutaneous lesions that arose synchronously, along with
      micrometastases to sentinel lymph nodes.

PMID- 18331572
TI  - Specific nasal symptoms and symptom-provoking factors may predict increased risk
      of developing COPD.
AB  - In a 1992 questionnaire study, we found that certain nasal symptoms and symptom
      provoking factors were associated with prevalence of self-reported chronic
      bronchitis/emphysema (CBE). In this follow-up study, we examined whether any
      nasal features could predict an increased incidence of self-reported physician's
      diagnosis of CBE/chronic obstructive pulmonary disease (COPD). In 2000, a survey
      was performed similar to the one in 1992. Of a paired follow-up group of 4933
      participants aged 28-67 years, 4280 (86.8%) returned the questionnaire. Odds
      ratios (ORs) for cumulative incidence (between 1992 and 2000) of self-reported
      physician-diagnosed CBE/COPD and asthma, respectively, were calculated by
      logistic regression with adjustment for age, gender and smoking habits. Reports
      of thick, yellow nasal discharge and nasal blockage in 1992 predicted incidence
      of CBE/COPD: OR 2.3 (1.2-4.2) and 1.8 (1.1-2.8) respectively. Moreover, nasal
      symptoms provoked by exposure to damp/cold air and tobacco smoke predicted
      CBE/COPD: OR 3.4 (1.9-6.0) and 2.5 (1.4-4.2). Nasal itching and nasal symptoms
      provoked by exposure to grass pollen and furred animals predicted incidence of
      asthma. These results suggest that certain nasal symptoms and nasal symptom
      provoking exposures, different from those commonly associated with asthma, may
      predict increased risk of developing CBE/COPD. This supports the possibility of
      nasal co-morbidity in COPD.

PMID- 18331573
TI  - Cancer incidence in patients with schizophrenia and their first-degree relatives 
      a meta-analysis.
AB  - OBJECTIVE: Controversy concerning cancer incidence in schizophrenia exists
      because of heterogeneous study findings. METHOD: A meta-analysis was performed on
      standardized incidence ratios (SIR) of cancer in patients with schizophrenia and
      first-degree relatives and compared with general population samples. RESULTS: The
      pooled overall cancer incidence in patients was not significantly increased (SIR
      = 1.05, CI 0.95-1.15). Lung cancer incidence was slightly increased (SIR = 1.31,
      CI 1.01-1.71), but was reduced after adjusting for smoking prevalence. The
      incidence of several cancers unrelated to smoking was reduced in patients. Breast
      cancer rates were significantly increased in female patients. The pooled overall
      cancer incidence in siblings (SIR = 0.89, CI 0.84-0.94) and parents (SIR = 0.90,
      CI 0.88-0.93) was significantly reduced. A meta-regression detected a significant
      relationship between cancer risk in the general population and relative risk in
      patients. CONCLUSION: The meta-analysis aided exploration of inconsistent study
      findings. There is a discrepancy between cancer risk exposure and cancer
      incidence in schizophrenia consistent with a protective effect.

PMID- 18331574
TI  - Dopamine and bipolar disorder.

PMID- 18331575
TI  - A challenging task for assessment of checking behaviors in obsessive-compulsive
      disorder.
AB  - OBJECTIVE: The present study concerns the objective and quantitative measurement
      of checking activity, which represents the most frequently observed compulsions
      in obsessive-compulsive disorder (OCD). To address this issue, we developed an
      instrumental task producing repetitive checking in OCD subjects. METHOD: Fifty
      OCD subjects and 50 normal volunteers (NV) were administered a delayed matching
      to-sample task that offered the unrestricted opportunity to verify the choice
      made. Response accuracy, number of verifications, and response time for choice
      taken to reflect the degree of uncertainty and doubt were recorded over 50
      consecutive trials. RESULTS: Despite similar levels of performance, patients with
      OCD demonstrated a greater number of verifications and a longer response time for
      choice before checking than NV. Such behavioral patterns were more pronounced in
      OCD subjects currently experiencing checking compulsions. CONCLUSION: The present
      task might be of special relevance for the quantitative assessment of checking
      behaviors and for determining relationships with cognitive processes.

PMID- 18331576
TI  - Association of IQ scores and school achievement with suicide in a 40-year follow
      up of a Swedish cohort.
AB  - OBJECTIVE: Few studies have investigated the association of childhood IQ and
      school achievement with suicide. The aim of this study was to investigate the
      association of childhood IQ with suicide in a cohort of Swedish women and men.
      METHOD: 21 809 subjects born in 1948 and 1953 who completed IQ and school tests
      at age 13 years have been followed until 2003. Information on paternal education
      and in-patient care for psychosis was linked using the Swedish personal
      identification number. RESULTS: There were 180 suicides amongst subjects with
      measured IQ. High IQ was associated with reduced suicide risk among men (OR per
      unit increase in age-adjusted model 0.90, 95% CI 0.83-0.99), while there was no
      statistical evidence of an association in women (OR 1.04, 95% CI 0.90-1.20).
      Among men with a history of psychosis, high IQ was associated with an increased
      risk of suicide. CONCLUSION: Low childhood IQ at age 13 years is associated with
      an increased risk of suicide in men but not in women; however, amongst those with
      psychosis, low IQ appears to be protective.

PMID- 18331577
TI  - Clinical case management of revolving door patients - a semi-randomized study.
AB  - OBJECTIVE: To assess the effectiveness of psychiatric clinical case management.
      METHOD: Subjects with at least three admissions in the previous 2 years were
      randomized into a clinical case management group (CMG; n = 122) and a standard
      care group (SCG; n = 95). Individuals who refused or were not located were
      included in a third, non-randomized no-treatment group (NTG; n = 153). Parameters
      assessed included utilization of in-patient services and psychosocial
      functioning. RESULTS: We found no difference between the CMG and the SCG in
      psychosocial functioning as evaluated by interviewers, and no difference between
      the three groups in hospitalization. In subjects' self-ratings, the CMG showed
      slight improvement in psychosocial functioning. CONCLUSION: Clinical case
      management did not prove itself superior to standard care in a revolving door
      population.

PMID- 18331578
TI  - Oligodipsia and dissociative experiences in borderline personality disorder.
AB  - OBJECTIVE: To test the frequency of attenuated fluid intake behavior
      (oligodipsia) in patients with borderline personality disorder (BPD) and to test
      if there is an inverse correlation between oligodipsia and the intensity of
      current dissociative experience in a pilot study. METHOD: Analyses were based on
      a sample of 15 BPD patients and 15 healthy controls. Fluid intake per diem and
      intensity of dissociative experience were measured by standardized self-reports
      daily for 7 days. RESULTS: The BPD patients ingested a significantly lower fluid
      volume per diem when compared with healthy controls (P < 0.001). We found a
      strong correlation between intensity of co-occurring dissociative experience and
      fluid intake or urine osmolality (r = 0.762 and 0.665), independently of sleep
      quality and general BPD symptom severity. CONCLUSION: The results indicate that
      oligodipsia may constitute a serious problem at least for a subgroup of BPD
      patients, and may be correlated with some of the most problematic symptoms of
      BPD.

PMID- 18331579
TI  - Applicants for stereotactic neurosurgery for psychiatric disorders: role of the
      Flemish advisory board.
AB  - OBJECTIVE: Research on stereotactic neurosurgery for psychiatric disorders (SNPD)
      is rapidly evolving. Knowledge on patients undergoing SNPD is of crucial
      importance. We describe applicants for SNPD and examine the necessity for a
      multidisciplinary advisory board. METHOD: Summary of the current practice of the
      Flemish advisory board (SNPD committee) and analysis of a questionnaire
      investigating the attitude of clinicians on SNPD. RESULTS: In 7 years, 91
      applications were submitted, nine patients did not fulfill diagnostic criteria
      for OCD, 65 patients received a positive recommendation, 50 SNPD procedures were
      performed. The prevalence of SNPD in the current year in Belgium is 0.6/million
      inhabitants. Ninety-seven per cent of clinicians consider the expertise and
      advice of the SNPD committee essential for indication setting. Forty-four percent
      of clinicians consider referral of a patient for capsulotomy, 82% for electrical
      brain stimulation. CONCLUSION: Neurosurgery is exclusively considered for severe,
      treatment-refractory psychiatric disorders. Clinicians consider the SNPD
      committee essential in the decision-making process prior to intervention.

PMID- 18331580
TI  - Encephalopathy with combined lithium-risperidone administration.
AB  - OBJECTIVE: Lithium-neuroleptics induced encephalopathy is a rare drug
      interaction. Here I am reporting a patient who developed reversible
      encepatholopathy with lithium-risperidone combination. METHOD: A single case
      report. RESULT: A patient of bipolar disorder, who presented with manic symptoms
      with psychotic feature, started with a combination of lithium and risperidone.
      Within few days, the patient developed encepatholopathy, which reversed upon
      discontinuation of lithium and risperidone. CONCLUSION: Combining lithium and
      neuroleptic is useful in treatment of bipolar disorder. However, encepatholapthy
      can be anticipated to result when lithium is used with high potency anti
      psychotic such as haloperidol and risperidone and there are baseline EEG
      abnormalities.

PMID- 18331581
TI  - The mental health impact of terrorism in Israel: a repeat cross-sectional study
      of Arabs and Jews.
AB  - OBJECTIVE: Since September 2000 Israeli society has been subjected to numerous
      deadly terror attacks. Few studies have studied the comparative mental health
      vulnerability of minorities and majorities to continuous terror attacks. METHOD:
      Two telephone surveys (N = 512 and 501) on two distinct representative samples of
      the Israeli population after 19 months and after 44 months of terror. The Arab
      minority and Jewish majority were compared on measures of exposure to terrorism,
      posttraumatic stress symptomatology, feeling depressed, coping, sense of safety,
      future orientation, and previous traumatic experiences. RESULTS: After 19 months
      of terrorist attacks Arab Israelis and Jewish Israelis reacted roughly similarly
      to the situation, however after 44 months of terror, posttraumatic symptom
      disorder in the Arab population increased three-fold, posttraumatic
      symptomatology doubled and resiliency almost disappeared. CONCLUSION: We suggest
      that certain conditions inherent to political conflict situations may potentially
      put minorities at risk and may only be observable as terrorism-related stressors
      become chronic.

PMID- 18331582
TI  - Regulation of dendritic spine morphology by an NMDA receptor-associated Rho
      GTPase-activating protein, p250GAP.
AB  - The NMDA receptor regulates spine morphological plasticity by modulating Rho
      GTPases. However, the molecular mechanisms for NMDA receptor-mediated regulation
      of Rho GTPases remain elusive. In this study, we show that p250GAP, an NMDA
      receptor-associated RhoGAP, regulates spine morphogenesis by modulating RhoA
      activity. Knock-down of p250GAP increased spine width and elevated the endogenous
      RhoA activity in primary hippocampal neurons. The increased spine width by
      p250GAP knock-down was suppressed by the expression of a dominant-negative form
      of RhoA. Furthermore, p250GAP is involved in NMDA receptor-mediated RhoA
      activation. In response to NMDA receptor activation, exogenously expressed green
      fluorescent protein (GFP)-tagged p250GAP was redistributed. Thus, these data
      suggest that p250GAP plays an important role in NMDA receptor-mediated regulation
      of RhoA activity leading to spine morphological plasticity.

PMID- 18331583
TI  - Neuropeptide Y stimulates retinal neural cell proliferation--involvement of
      nitric oxide.
AB  - Neuropeptide Y (NPY) is a 36 amino acid peptide widely present in the CNS,
      including the retina. Previous studies have demonstrated that NPY promotes cell
      proliferation of rat post-natal hippocampal and olfactory epithelium precursor
      cells. The aim of this work was to investigate the role of NPY on cell
      proliferation of rat retinal neural cells. For this purpose, primary retinal cell
      cultures expressing NPY, and NPY Y(1), Y(2), Y(4) and Y(5) receptors [Alvaro et
      al., (2007) Neurochem. Int., 50, 757] were used. NPY (10-1000 nM) stimulated cell
      proliferation through the activation of NPY Y(1), Y(2) and Y(5) receptors. NPY
      also increased the number of proliferating neuronal progenitor cells
      (BrdU(+)/nestin(+) cells). The intracellular mechanisms coupled to NPY receptors
      activation that mediate the increase in cell proliferation were also
      investigated. The stimulatory effect of NPY on cell proliferation was reduced by
      L-nitroarginine-methyl-esther (L-NAME; 500 microM), a nitric oxide synthase
      inhibitor, 1H-[1,2,4]oxadiazolo-[4, 3-a]quinoxalin-1-one (ODQ; 20 microM), a
      soluble guanylyl cyclase inhibitor or U0126 (1 microM), an inhibitor of the
      extracellular signal-regulated kinase 1/2 (ERK 1/2). In conclusion, NPY
      stimulates retinal neural cell proliferation, and this effect is mediated through
      nitric oxide-cyclic GMP and ERK 1/2 pathways.

PMID- 18331584
TI  - Mechanisms of DJ-1 neuroprotection in a cellular model of Parkinson's disease.
AB  - Mitochondrial dysfunction, proteasome inhibition, and alpha-synuclein aggregation
      are thought to play important roles in the pathogenesis of Parkinson's disease
      (PD). Rare cases of early-onset PD have been linked to mutations in the gene
      encoding DJ-1, a protein with antioxidant and chaperone functions. In this study,
      we examined whether DJ-1 protects against various stresses involved in PD, and we
      investigated the underlying mechanisms. Expression of wild-type DJ-1 rescued
      primary dopaminergic neurons from toxicity elicited by rotenone, proteasome
      inhibitors, and mutant alpha-synuclein. Neurons with reduced levels of endogenous
      DJ-1 were sensitized to each of these insults, and DJ-1 mutants involved in
      familial PD exhibited decreased neuroprotective activity. DJ-1 alleviated
      rotenone toxicity by up-regulating total intracellular glutathione. In contrast,
      inhibition of alpha-synuclein toxicity by DJ-1 correlated with up-regulation of
      the stress-inducible form of Hsp70. RNA interference studies revealed that this
      increase in Hsp70 levels was necessary for DJ-1-mediated suppression of alpha
      synuclein aggregation, but not toxicity. Our findings suggest that DJ-1 acts as a
      versatile pro-survival factor in dopaminergic neurons, activating different
      protective mechanisms in response to a diverse range of PD-related insults.

PMID- 18331585
TI  - Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y
      cells.
AB  - Alzheimer's disease (AD) is a common neurodegenerative disorder, but the
      initiating molecular processes contributing to neuronal death are not well
      understood. AD is associated with elevated soluble and aggregated forms of
      amyloid beta (Abeta) and with oxidative stress. Furthermore, there is increasing
      evidence for a detrimental role of iron in the pathogenic process. In this
      context, iron chelation by compounds such as 3-hydroxypyridin-4-one, deferiprone
      (Ferriprox) may have potential neuroprotective effects. We have evaluated the
      possible neuroprotective actions of deferiprone against a range of AD-relevant
      insults including ferric iron, H(2)O(2) and Abeta in primary mouse cortical
      neurones. We have investigated the possible neuroprotective actions of
      deferiprone (1, 3, 10, 30 or 100 microM) in primary neuronal cultures following
      exposure to ferric iron [ferric nitrilotriacetate (FeNTA); 3 and 10 microM],
      H(2)O(2) (100 microM) or Abeta1-40 (3, 10 and 20 microM). Cultures were treated
      with deferiprone or vehicle either immediately or up to 6 h after the insult in a
      24-well plate format. In order to elucidate a possible neuroprotective action of
      deferiprone against Parkinson's disease relevant insults another group of
      experiments were performed in the human neuroblastoma catecholaminergic SHSY-5Y
      cell line. SHSY-5Y cells were treated with MPP(+) iodide, the active metabolite
      of the dopaminergic neurotoxin MPTP and the neuroprotective actions of
      deferiprone evaluated. Cytotoxicity was assessed at 24 h by lactate dehydrogenase
      release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide turnover
      (FeNTA and hydrogen peroxide) and morphometric analysis of cell viability by
      Hoechst 33324/propidium iodide (FeNTA, Abeta and MPP(+)) or 6-carboxyfluorescein
      diacetate and annexin V-Cy3 (Abeta). The present study demonstrates that
      deferiprone protects against FeNTA, hydrogen peroxide, MPP(+) and Abeta1-40
      induced neuronal cell death in vitro, which is consistent with previous in vitro
      and in vivo studies that have demonstrated similar protection with other iron
      chelators.

PMID- 18331586
TI  - Promoter-specific induction of the phosphatase SHP-1 by viral infection and
      cytokines in CNS glia.
AB  - We have previously shown that the protein tyrosine phosphatase SHP-1 is highly
      expressed in CNS glia and is an important modulator of cytokine signaling. As
      such, mice genetically lacking SHP-1 display constitutive myelin abnormalities,
      severe virus-induced demyelinating disease, and defects in innate anti-viral
      responses in the CNS. In this study, we show the differential distribution of the
      SHP-1 promoter-specific transcripts and demonstrate that several cytokines
      significantly induce SHP-1 expression in CNS glia. Consistent with these cytokine
      effects, infection with a neurotropic virus both in vitro and in vivo up
      regulates SHP-1 transcripts and protein in CNS cells. Using CNS glial cultures of
      gene knockout mice, we show that interferons-beta and interferons-gamma act
      through STAT-1 and interferon regulatory factor-1 to induce the SHP-1 promoter I
      transcripts. Conversely, interferons-beta and IL-6 act through STAT-3 to induce
      SHP-1 promoter II transcripts. This study demonstrates that interferons and other
      cytokines associated with virus infections in the CNS can significantly induce
      the expression of SHP-1 through STAT-1/3 activity and provides a better
      understanding of the molecular mechanisms regulating cytokine-induced expression
      important for multiple homeostatic functions of SHP-1 in the CNS.

PMID- 18331587
TI  - Regulation of CB1 cannabinoid receptor internalization by a promiscuous
      phosphorylation-dependent mechanism.
AB  - Agonists stimulate cannabinoid 1 receptor (CB(1)R) internalization. Previous work
      suggests that the extreme carboxy-terminus of the receptor regulates this
      internalization - likely through the phosphorylation of serines and threonines
      clustered within this region. While truncation of the carboxy-terminus (V460Z
      CB(1)) and consequent removal of these putative phosphorylation sites prevents
      endocytosis in AtT20 cells, the residues necessary for CB(1)R internalization
      remain elusive. To determine the structural requirements for internalization, we
      evaluated endocytosis of carboxy-terminal mutant CB(1)Rs stably expressed in
      HEK293 cells. In contrast to AtT20 cells, V460Z CB(1)R expressed in HEK293 cells
      internalized to the same extent and with similar kinetics as the wild-type
      receptor. However, mutation of serine and/or threonine residues within the
      extreme carboxy-terminal attenuated internalization when these receptors were
      expressed in HEK293 cells. These results establish that the extreme carboxy
      terminal phosphorylation sites are not required for internalization of truncated
      receptors, but are required for internalization of full-length receptors in
      HEK293 cells. Analysis of beta-arrestin-2 recruitment to mutant CB(1)R suggests
      that putative carboxy-terminal phosphorylation sites mediate beta-arrestin-2
      translocation. This study indicates that the local cellular environment affects
      the structural determinants of CB(1)R internalization. Additionally,
      phosphorylation likely regulates the internalization of (full-length) CB(1)Rs.

PMID- 18331588
TI  - Experimental evidence for diel variations of the carbon isotope composition in
      leaf, stem and phloem sap organic matter in Ricinus communis.
AB  - Carbon isotope fractionation in metabolic processes following carboxylation of
      ribulose-1,5-bisphosphate (RuBP) is not as well described as the discrimination
      during photosynthetic CO(2) fixation. However, post-carboxylation fractionation
      can influence the diel variation of delta(13)C of leaf-exported organic matter
      and can cause inter-organ differences in delta(13)C. To obtain a more mechanistic
      understanding of post-carboxylation modification of the isotopic signal as
      governed by physiological and environmental controls, we combined the modelling
      approach of Tcherkez et al., which describes the isotopic fractionation in
      primary metabolism with the experimental determination of delta(13)C in leaf and
      phloem sap and root carbon pools during a full diel course. There was a strong
      diel variation of leaf water-soluble organic matter and phloem sap sugars with
      relatively (13)C depleted carbon produced and exported during the day and
      enriched carbon during the night. The isotopic modelling approach reproduces the
      experimentally determined day-night differences in delta(13)C of leaf-exported
      carbon in Ricinus communis. These findings support the idea that patterns of
      transitory starch accumulation and remobilization govern the diel rhythm of
      delta(13)C in organic matter exported by leaves. Integrated over the whole 24 h
      day, leaf-exported carbon was enriched in (13)C as compared with the primary
      assimilates. This may contribute to the well-known--yet poorly explained-
      relative (13)C depletion of autotrophic organs compared with other plant parts.
      We thus emphasize the need to consider post-carboxylation fractionations for
      studies that use delta(13)C for assessing environmental effects like water
      availability on ratio of mole fractions of CO(2) inside and outside the leaf
      (e.g. tree ring studies), or for partitioning of CO(2) fluxes at the ecosystem
      level.

PMID- 18331589
TI  - Photorespiration in C4 grasses remains slow under drought conditions.
AB  - The CO(2)-concentrating mechanism present in C(4) plants decreases the oxygenase
      activity of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and,
      consequently, photorespiratory rates in air. Under drought conditions, the
      intercellular CO(2) concentration may decrease and cause photorespiration to
      increase. The C(4) grasses Paspalum dilatatum Poiret, Cynodon dactylon (L.) Pers.
      and Zoysia japonica Steudel were grown in soil and drought was imposed by ceasing
      to provide water. Net CO(2) assimilation (A) and stomatal conductance to water
      vapour decreased with leaf dehydration. Decreased carbon and increased oxygen
      isotope composition were also observed under drought. The response of A to CO(2)
      suggested that the compensation point was zero in all species irrespective of the
      extent of drought stress. A slight decrease of A as O(2) concentration increased
      above 10% provided evidence for slow photorespiratory gas exchanges. Analysis of
      amino acids contained in the leaves, particularly the decrease of glycine after
      30 s in darkness, supported the presence of slow photorespiration rates, but
      these were slightly faster in Cynodon dactylon than in Paspalum dilatatum and
      Zoysia japonica. Although the contents of glycine and serine increased with
      dehydration and mechanistic modelling of C(4) photosynthesis suggested slightly
      increased photorespiration rates in proportion to photosynthesis, the results
      provide evidence that photorespiration remained slow under drought conditions.

PMID- 18331590
TI  - A novel secreted protease from Pseudomonas aeruginosa activates NF-kappaB through
      protease-activated receptors.
AB  - The Pseudomonas aeruginosa-derived alkaline protease (AprA), elastase A (LasA),
      elastase B (LasB) and protease IV are considered to play an important role in
      pathogenesis of this organism. Although the sequence analysis of P. aeruginosa
      genome predicts the presence of several genes encoding other potential proteases
      in the genome, little has been known about the proteases involving in
      pathogenesis. Recently, Porphyromonas gingivalis gingipains and Serratia
      marcescens serralysin have been shown to activate protease-activated receptor 2
      (PAR-2), thereby modulating host inflammatory and immune responses. Accordingly,
      we hypothesized that unknown protease(s) from P. aeruginosa would also modulate
      such responses through PARs. In this study, we found that P. aeruginosa produces
      a novel large exoprotease (LepA) distinct from known proteases such as AprA,
      LasA, LasB and protease IV. Sequence analysis of LepA showed a molecular feature
      of the proteins transported by the two-partner secretion pathway. Our results
      indicated that LepA activates NF-kappaB-driven promoter through human PAR-1, -2
      or -4 and cleaves the peptides corresponding to the tethered ligand region of
      human PAR-1, -2 and -4 at a specific site with exposure of their tethered
      ligands. Considered together, these results suggest that LepA would require PARs
      to modulate various host responses against bacterial infection.

PMID- 18331591
TI  - Contributions of proteomics to understanding phagosome maturation.
AB  - In metazoans macrophage cells use phagocytosis, the process of engulfing large
      particles, to control the spread of pathogens in the body, to clear dead or dying
      cells, and to aid in tissue remodelling, while the same process is also used by
      unicellular eukaryotes to ingest food. Phagocytosing cells essentially swallow
      the particles, trapping them in vacuoles called phagosomes that go through a
      series of maturation steps, culminating in the destruction of the internalized
      cargo. Because of their central role in innate immunity and their relatively
      simple structure (one membrane bilayer surrounding a single particle), phagosomes
      have been a popular subject for organelle proteomics studies. Qualitative
      proteomic technologies are now very sensitive so hundreds of different proteins
      have been identified in phagosomes from several species, revealing new properties
      of these intriguing compartments. More recently, quantitative proteomic
      approaches have also been applied, shedding new light on the dynamics and
      composition of maturing phagosomes. In this review we summarize the studies that
      have applied proteomic technologies to phagosomes and how they have changed our
      understanding of phagosome biology.

PMID- 18331592
TI  - ZAK: a MAP3Kinase that transduces Shiga toxin- and ricin-induced proinflammatory
      cytokine expression.
AB  - Shiga toxins (Stxs) and ricin initiate damage to host cells by cleaving a single
      adenine residue on the alpha-sarcin loop of the 28S ribosomal RNA. This molecular
      insult results in a cascade of intracellular events termed the ribotoxic stress
      response (RSR). Although Stxs and ricin have been shown to cause the RSR, the
      mitogen-activated protein kinase kinase kinase (MAP3K) that transduces the signal
      from intoxicated ribosomes to activate SAPKinases has remained elusive. We show
      in vitro that DHP-2 (7-[3-fluoro-4-aminophenyl-(4-(2-pyridin-2-yl-5,6-dihydro-4H
      pyrrolo[1,2-b]pyrazol-3-yl))]-quinoline), a zipper sterile-alpha-motif kinase
      (ZAK)-specific inhibitor, blocks Stx2/ricin-induced SAPKinase activation.
      Treatment of cells with DHP-2 also blocks Stx2/ricin-mediated upregulation of the
      proinflammatory cytokine interleukin-8 and results in a modest but statistically
      significant improvement in cell viability following Stx2/ricin treatment. Finally
      we show that siRNA directed against the N-terminus of ZAK diminishes Stx2/Ricin
      induced SAPKinase activation. Together, these data demonstrate that a ZAK
      isoform(s) is the MAP3Kinase that transduces the RSR. Therefore, ZAKalpha and/or
      beta isoforms may act as potential therapeutic target(s) for treating Stx/ricin
      associated illnesses. Furthermore, a small molecule inhibitor like DHP-2 may
      prove valuable in preventing the Stx/ricin-induced proinflammatory and/or
      apoptotic effects that are thought to contribute to pathogenesis by Stx-producing
      Escherichia coli and ricin.

PMID- 18331593
TI  - Acute splenic sequestration complicating sickle cell disease.

PMID- 18331594
TI  - Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paper.
AB  - Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite
      recent advances in immunophenotyping and molecular cytogenetics, leading to a
      better understanding of the underlying cell biology of the prolymphocytic
      leukaemias, prognosis for these patients remains poor. Purine analogues and
      monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia
      although further studies are warranted. Monoclonal antibody therapy with
      alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia
      (T-PLL) but responses are still transient and further disease progression is
      inevitable. While allogeneic stem cell transplant is an attractive option, due to
      the older age group of T-PLL patients the morbidity and mortality associated with
      the procedure is significant.

PMID- 18331595
TI  - Bisphosphonates may retrieve endothelial function in vascular diseases similar to
      statins' effects.

PMID- 18331596
TI  - A hemophiliac pseudotumor mimicking an incisional hernia in outward appearance.

PMID- 18331597
TI  - Staphylokinase reduces plasmin formation by endogenous plasminogen activators.
AB  - Hyperfibrinolysis is a consequence of imbalance between fibrinolytic activators
      and their inhibitors. Increased levels of circulating plasminogen (Plg)
      activators such as tissue- or urokinase-type plasminogen activators (tPA or uPA
      respectively) are the most common causes of hyperfibrinolysis, occasionally
      causing major hemorrhages. We found that staphylokinase (SAK), a well-known Plg
      activator of bacterial origin, inhibits Plg activation mediated by endogenous tPA
      and uPA. Furthermore, mixture of SAK with tPA led to a significantly reduced Plg
      dependent fibrinolysis. This inhibitory effect was exerted through direct action
      of SAK on Plg rather than indirectly on tPA or uPA. Inhibition of Plg activation
      by SAK is readily abrogated by interaction of SAK with human neutrophil peptides
      (HNPs). Finally, we show that NH2-terminal residues of SAK are important for the
      inhibitory effect of SAK on tPA- and uPA-mediated Plg activation. In conclusion,
      SAK reduces tPA/uPA-mediated Plg activation by means of SAK.Plg complex
      formation, consequently downregulating tPA/uPA-induced fibrinolysis.

PMID- 18331598
TI  - Serum concentrations of DKK-1 correlate with the extent of bone disease in
      patients with multiple myeloma.
AB  - OBJECTIVES: Lytic bone disease is a hallmark of multiple myeloma (MM) and is
      caused by osteoclast activation and osteoblast inhibition. Secretion of Dickkopf
      (DKK)-1 by myeloma cells is a major factor which causes inhibition of osteoblast
      precursors. So far, there is no study showing a significant difference in serum
      DKK-1 levels in MM patients with or without lytic bone lesions. METHODS: DKK-1
      serum levels were quantified in 184 untreated MM patients and 33 monoclonal
      gammopathy of undetermined significance (MGUS) patients by ELISA, using a
      monoclonal anti-DKK-1 antibody. RESULTS: Serum DKK-1 was elevated in MM as
      compared with MGUS (mean 11 963 pg/mL vs. 1993 pg/mL; P < 0.05). Serum DKK-1
      levels significantly correlated with myeloma stage according to Durie and Salmon
      (mean 2223 pg/mL vs. 15 209 pg/mL in stage I and II/III, respectively; P =
      0.005). Importantly, myeloma patients without lytic lesions in conventional
      radiography had significantly lower DKK-1 levels than patients with lytic bone
      disease (mean 3114 pg/mL vs. 17 915 pg/mL; P = 0.003). Of interest, serum DKK-1
      correlated with the number of bone lesions (0 vs. 1-3 vs. >3 lesions: 3114 pg/mL
      vs. 3559 pg/mL vs. 24 068 pg/mL; P = 0.002). CONCLUSION: Using a large series of
      myeloma patients, we could show for the first time a correlation between DKK-1
      serum concentration and the amount of lytic bone disease, indicating that DKK-1
      is an important factor for the extent of bone disease and supporting the
      hypothesis of DKK-1 as a therapeutic target in myeloma bone disease.

PMID- 18331599
TI  - FOXP3 positive regulatory T-cells in cutaneous and systemic CD30 positive T-cell
      lymphoproliferations.
AB  - The CD30-positive lymphoproliferations encompass a spectrum of disorders that
      share histological and phenotypic similarities but differ markedly in clinical
      behaviour. The basis for this diversity is not known, but it has been proposed
      that immune suppression by cytokines and/or regulatory T-cells (Tregs) may be
      implicated. In this study, skin biopsies from lymphomatoid papulosis (LyP) (n =
      14), primary cutaneous anaplastic large cells lymphoma (C-ALCL) (n = 13) and
      systemic anaplastic large cells lymphoma (S-ALCL) with (n = 9) or without (n = 6)
      ALK expression were examined by immunohistology for FOXP3 expression in tumour
      cells and tumour infiltrating Tregs. Labelling of a majority of the neoplastic
      cells was seen in one case of C-ALCL. Another three cases (one LyP and two C
      ALCL) displayed weak labelling of very occasional atypical T-cells. In the
      remaining 38 cases the atypical lymphoid infiltrate was FOXP3 negative. By
      contrast, all biopsies contained tumour infiltrating FOXP3-positive Tregs.
      Significant higher numbers were recorded in ALK negative S-ALCL and LyP than in C
      ALCL and S-ALCL positive for ALK. In conclusion, it is shown that FOXP3
      expression in cutaneous and systemic CD30-positive lymphoproliferations is
      generally confined to tumour infiltrating Tregs. These cells may have influence
      upon the clinical behaviour, possibly depending upon the net degree of Treg
      mediated immune suppression of tumour cells relative to tumour infiltrating,
      cytotoxic effector cells, thereby implicating the more favourable outcome of LyP
      compared to C-ALCL.

PMID- 18331600
TI  - A case of coexistence between JAK2V617F and BCR /ABL.

PMID- 18331602
TI  - Platelet-derived growth factor may be associated with fibrosis in a Down syndrome
      patient with transient myeloproliferative disorder.
AB  - Transient myeloproliferative disorder (TMD) is experienced by approximately 10%
      of neonates with Down syndrome (DS). Most TMD is asymptomatic and the patients
      undergo spontaneous remission within a few months. However, some cases are fatal
      because of systemic organ dysfunctions including hepatic fibrosis. Some cytokines
      such as platelet-derived growth factor (PDGF) may be involved in the development
      of hepatic fibrosis in TMD. The report describes a fatal case of TMD accompanying
      DS. The patient presented with pulmonary hypertension and hepatic failure. An
      autopsy disclosed severe fibrosis in the lung, liver, kidney and pancreas.
      Immunohistochemical analysis revealed high expression of PDGF receptor beta in
      the severe fibrotic areas of the fibrotic tissues. A real-time polymerase chain
      reaction (PCR) analysis demonstrated the expression of PDGFalpha and PDGFbeta in
      the peripheral blood samples of the patient. The finding indicates that the PDGF
      pathway may play an important role in the fibrosis of several organs in patients
      with TMD.

PMID- 18331601
TI  - CNOP (mitoxantrone) chemotherapy is inferior to CHOP (doxorubicin) in the
      treatment of patients with aggressive non-Hodgkin lymphoma (meta-analysis).
AB  - Mitoxantrone has a broad anti-tumour activity including lymphoma with potentially
      less cardiotoxicity than doxorubicin, which may be of particular importance in
      elderly patients. However, an important issue is whether mitoxantrone is as
      efficacious as doxorubicin in the treatment of aggressive lymphomas. Through
      search of several relevant databases and contacts with lymphoma investigators
      worldwide, we identified nine randomised studies of previously untreated patients
      comparing CHOP and CNOP chemotherapy in aggressive non-Hodgkin lymphoma. Five
      trials were included where doxorubicin (50 mg/m2) was compared with mitoxantrone
      (10-12 mg/m2) and the interval between chemotherapy courses was 3-4 wk. In none
      of these trials rituximab was used. Odds ratios of complete remission (CR) were
      pooled using a fixed effects model, and odds ratios of overall survival (OS) were
      pooled using a random effects model. CNOP was significantly inferior to CHOP with
      regard to CR rate. CNOP was also inferior, but not significantly to CHOP with
      regard to OS. No formal testing of side effects could be made. However, the two
      regimens were equally myelosuppressive. Clinical evidence of symptomatic
      congestive heart disease was not more frequent among patients treated with CHOP.
      However, gastrointestinal toxicities and alopecia were more common in this group.
      CHOP chemotherapy is more efficacious than CNOP at equitoxic (myelosuppression)
      doses. CHOP is, however, associated with more alopecia and gastrointestinal
      toxicity.

PMID- 18331603
TI  - Clinical relevance of soluble HLA class I molecules in Waldenstrom
      Macroglobulinemia.
AB  - OBJECTIVES: Waldenstrom Macroglobulinemia (WM) is a B-cell neoplasm characterised
      by secretion of IgM by lymphoplasmacytic bone marrow cells and by cytopenias and
      hypogammaglobulinemia in a subset of patients. Beta-2 microglobulin (b2m) is a
      major prognostic factor in WM and the heavy chain of HLA class I molecules, which
      are known to have immunosuppressive properties and have been implicated in the
      pathogeny of several malignancies. METHODS: We assessed the serum levels of the
      total soluble HLA-I molecules and the HLA-Gs molecules in 105 patients with IgM
      related disorders [WM (n = 42) and IgM MGUS (n = 63)], and compared the results
      to 41 healthy subjects. RESULTS: We found higher levels of HLA-Is in WM, compared
      to IgM MGUS and healthy donors. HLA-Gs levels were similar in WM and in IgM MGUS,
      but higher than in healthy donors. The association between HLA-Is at the cut-off
      of 1.8 microg/mL and known markers of poor prognosis was then evaluated among WM
      patients using univariate and multivariate methods. Based on this, high HLA-Is
      level was strongly associated with high serum beta2M level >3 mg/L [OR = 2, (CI
      95% 1.1-5.7); P = 0.04], age > 65 yrs [OR = 1.5, (CI 95% 0.5-4.1), P = 0.06] and
      haemoglobin < or =11.5 g/dL [OR = 3.3, (CI 95% 1.2-9.7); P = 0.03]. High levels
      of serum HLA-Is were also found in patients with cryoglobulinemia, however
      irrespectively of WM or IgM-MGUS status. CONCLUSION: Together our results suggest
      a possible role for soluble MHC class I molecules in WM disease. Further
      investigations are necessary to further demonstrate the prognostic impact of
      soluble MHC class I molecules in Waldenstrom Macroglobulinemia.

PMID- 18331604
TI  - Percutaneous ethanol injection therapy: a surgery-sparing treatment for primary
      hyperparathyroidism.
AB  - OBJECTIVE: To describe our 3-year experience in the long-term efficacy and safety
      of percutaneous ethanol injection therapy (PEIT), as an alternative to surgery
      for the management of patients with primary hyperparathyroidism (p-HPT). DESIGN:
      Prospective study with a mean follow-up of 19.6 +/- 10.6 months. PATIENTS: Our
      study population included 19 consecutive high risk patients with p-HPT, who met
      the criteria for surgery. MEASUREMENTS: Under ultrasonic guidance, ethanol (95%)
      was injected into parathyroid glands with a volume of >or= 0.15 cm(3). With the
      aim of normalizing intact parathormone (iPTH) values, repeated ethanol injections
      were carried out, in an interval of 2 weeks, until normalization of iPTH was
      reached or until no residual blood supply was detected by ultrasound in the
      gland. Biochemical parameters were monitored throughout the study. RESULTS: At 6
      month follow-up, normalization of iPTH levels (10-65 ng/l) was achieved in 11
      (58%) patients (responders). Of the eight remaining patients (nonresponders), six
      patients had reduced (but not normalized) iPTH levels and two patients required
      parathyroid surgery. Seventeen (11 responders and 6 nonresponders) of the 19
      patients (89.5%) became normocalcaemic (serum Ca <or= 2.57 mmol/l) and remained
      so for a mean follow-up of 21 months (8-39 months). The odds ratio (P < 0.05) of
      response vs. no response to PEIT was 16.7-fold for pretreatment iPTH < 200 vs. >
      200 ng/l. The only complication was a transient dysphonia noticed in three
      patients. CONCLUSIONS: PEIT is a safe and effective nonsurgical treatment for
      patients with p-HPT, who are unsuitable for surgical intervention.

PMID- 18331606
TI  - Associations with multiple pituitary hormone deficiency in patients with an
      ectopic posterior pituitary gland.
AB  - INTRODUCTION: The presence of an ectopic posterior pituitary gland (EPP) on
      magnetic resonance imaging (MRI) is associated with hypopituitarism with one or
      more hormone deficiencies. We aimed to identify risk factors for having multiple
      pituitary hormone deficiency (MPHD) compared to isolated growth hormone
      deficiency (IGHD) in patients with an EPP. METHODS: In 67 patients (45 male) with
      an EPP on MRI, the site (hypothalamic vs. stalk) and surface area (SA) [ x
      (maximum diameter/2) x (maximum height/2), mm(2)] of the EPP were recorded and
      compared in patients with IGHD and MPHD in relation to clinical characteristics.
      RESULTS: In MPHD (n = 32) compared to IGHD (n = 35) patients: age of presentation
      was younger (1.4 [0.1-10.7]vs. 4.0 [0.1-11.3] years, P = 0.005), major incidents
      during pregnancy were increased (47%vs. 20%, P = 0.02) as were admissions to a
      neonatal intensive care unit (NICU) (60%vs. 26%, P = 0.04), whilst EPP SA was
      lower (12.3 [2.4-34.6]vs. 25.7 [6.9-48.2] mm(2), P < 0.001). In patients with a
      hypothalamic (n = 56) compared to a stalk sited EPP (n = 11): prevalence of MPHD
      was greater (55%vs. 9%,P = 0.05) and EPP surface area was smaller (17.3 [2.4
      48.2]vs. 25.3 [11.8-38.5] mm(2), P < 0.001). In regression analysis, after
      adjusting for age, presence of MPHD was associated with: major incidents during
      pregnancy (RR 6.8 [95%CI 1.2-37.7]), hypothalamic EPP site (RR 10.9 [1.0-123.9])
      and small EPP SA (RR 2.5 [1.0-5.0] for tertiles of SA). CONCLUSION: In patients
      with an EPP, adverse antenatal events, size (small) and position (hypothalamic)
      of the posterior pituitary gland on MRI were associated with MPHD. These findings
      suggest that adverse factors during pregnancy may be important for the
      development of an EPP.

PMID- 18331605
TI  - Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic
      athletes and controls: a cross-sectional study.
AB  - OBJECTIVES: Neuroendocrine factors may predict which athletes develop amenorrhea
      and which athletes remain eugonadal. Specifically, ghrelin and leptin have been
      implicated in regulation of GnRH secretion, with ghrelin having inhibitory and
      leptin, facilitatory effects. We hypothesized that adolescent athletes with
      amenorrhea (AA) would have higher ghrelin and lower leptin levels than
      eumenorrheic athletes (EA) and would predict levels of gonadal steroids. DESIGN:
      Cross-sectional. SUBJECTS AND MEASUREMENTS: We enrolled 58 girls, 21 AA, 19 EA
      and 18 nonathletic controls 12-18 years old. Fasting blood was drawn for active
      ghrelin, leptin, E(2) and testosterone. Athletes were > 85% of ideal body weight
      for age based on body mass index (BMI). RESULTS: AA girls had lower BMI than EA
      and controls (P = 0.003). Log ghrelin was higher in AA than in EA and controls (P
      < 0.0001), and remained higher after controlling for BMI Z-scores. Leptin was
      lower in AA than in the other groups (P < 0.0001), however, the differences did
      not persist after controlling for BMI Z-scores. Testosterone was lower in AA than
      in EA and controls (P = 0.002) and log E(2) trended lower in AA (P = 0.07). We
      observed inverse associations of log active ghrelin with testosterone (P = 0.01),
      and positive associations of leptin with testosterone and log E(2) (P = 0.02 and
      0.009). CONCLUSION: Higher ghrelin levels, even after controlling for BMI, and
      lower leptin in AA compared with EA and controls, and their inverse and positive
      associations, respectively, with gonadal steroids suggest endocrine perturbations
      that may explain why hypogonadism occurs in some but not all athletes.

PMID- 18331607
TI  - The effect of dipeptidyl peptidase-4 inhibition on gastric volume, satiation and
      enteroendocrine secretion in type 2 diabetes: a double-blind, placebo-controlled
      crossover study.
AB  - OBJECTIVES: The incretin hormone glucagon-like peptide-1 (GLP-1) retards gastric
      emptying and decreases caloric intake. It is unclear whether increased GLP-1
      concentrations achieved by inhibition of the inactivating enzyme dipeptidyl
      peptidase-4 (DPP-4) alter gastric volumes and satiation in people with type 2
      diabetes. METHODS: In a double-blind, placebo-controlled crossover design, 14
      subjects with type 2 diabetes received vildagliptin (50 mg bid) or placebo for 10
      days in random order separated by a 2-week washout. On day 7, fasting and
      postmeal gastric volumes were measured by a (99m)Tc single-photon emission
      computed tomography (SPECT) method. On day 8, a liquid Ensure meal was consumed
      at 30 ml/min, and maximum tolerated volume (MTV) and symptoms 30 min later were
      measured using a visual analogue scale (VAS) to assess effects on satiation. On
      day 10, subjects ingested water until maximum satiation was achieved. The volume
      ingested was recorded and symptoms similarly measured using a VAS. RESULTS:
      Vildagliptin raised plasma GLP-1 concentrations. However, fasting (248 +/- 21 vs.
      247 +/- 19 ml, P = 0.98) and fed (746 +/- 28 vs. 772 +/- 26 ml, P = 0.54) gastric
      volumes did not differ when subjects received vildagliptin or placebo. Treatment
      with vildagliptin did not alter the MTV of Ensure (1657 +/- 308 vs. 1389 +/- 197
      ml, P = 0.15) or water compared to placebo (1371 +/- 141 vs. 1172 +/- 156 ml, P =
      0.23). Vildagliptin was associated with decreased peptide YY (PYY) concentrations
      60 min after initiation of the meal (166 +/- 27 vs. 229 +/- 34 pmol/l, P = 0.01).
      CONCLUSIONS: Vildagliptin does not alter satiation or gastric volume in people
      with type 2 diabetes despite elevated GLP-1 concentrations. Compensatory changes
      in enteroendocrine secretion could account for the lack of gastrointestinal
      symptoms.

PMID- 18331608
TI  - Analysis of the PTPN11 gene in idiopathic short stature children and Noonan
      syndrome patients.
AB  - BACKGROUND: Mutations in the PTPN11 gene are the main cause of Noonan syndrome
      (NS). The presence of some NS features is a frequent finding in children with
      idiopathic short stature (ISS). These children can represent the milder end of
      the NS clinical spectrum and PTPN11 is a good candidate for involvement in the
      pathogenesis of ISS. OBJECTIVE: To evaluate the presence of mutations in PTPN11
      in ISS children who presented NS-related signs and in well-characterized NS
      patients. PATIENTS AND METHODS: We studied 50 ISS children who presented at least
      two NS-associated signs but did not fulfil the criteria for NS diagnosis. Forty
      nine NS patients diagnosed by the criteria of van der Burgt et al. were used to
      assess the adequacy of these criteria to select patients for PTPN11 mutation
      screening. The coding region of PTPN11 was amplified by polymerase chain reaction
      (PCR), followed by direct sequencing. RESULTS: No mutations or polymorphisms were
      found in the coding region of the PTPN11 gene in ISS children. Nineteen of the 49
      NS patients (39%) presented mutations in PTPN11. No single characteristic enabled
      us to distinguish between NS patients with or without PTPN11 mutations.
      CONCLUSION: Considering that no mutations were found in the present cohort with
      NS-related signs, it is unlikely that mutations would be found in unselected ISS
      children. The van der Burgt et al. criteria are adequate in attaining NS
      diagnosis and selecting patients for molecular studies. Mutations in the PTPN11
      gene are commonly involved in the pathogenesis of NS but are not a common cause
      of ISS.

PMID- 18331609
TI  - Association of race, body fat and season with vitamin D status among young women:
      a cross-sectional study.
AB  - OBJECTIVE: The purpose of this study was to provide an estimate of vitamin D
      status in young women residing in south-east Texas and to determine factors that
      predict 25-hydroxyvitamin D (25-OHD) concentration. DESIGN: A cross-sectional
      study was conducted on 800 non-Hispanic white, non-Hispanic black, and Hispanic
      women 16-33 years of age, who were seen in an outpatient clinic. MEASUREMENTS:
      Information was obtained on race, smoking, exercise and dietary intake of vitamin
      D. Percentage total body fat (%TBF) was assessed using dual-energy X-ray
      absorptiometry (DXA). Exposure to sunlight was estimated by examining national
      records of temperature, hours of daylight and UV index for the latitude of the
      study site. To determine the relationship between 25-OHD and %TBF, season, race,
      body mass index (BMI), dietary vitamin D, age and smoking in a multivariate
      context, stepwise linear regression analysis was performed. RESULTS: Serum 25-OHD
      levels differed among the racial groups (all pairwise differences P < 0.001),
      with the lowest value among non-Hispanic blacks (37.7 nmol/l) and the highest
      value among non-Hispanic whites (71.8 nmol/l). Among Hispanics, mean serum 25-OHD
      was 47.9 nmol/l. Serum 25-OHD was negatively associated with %TBF (r = -0.28),
      BMF (r = -0.36) and TBF (r = -0.33), all P < 0.001, and positively associated
      with dietary vitamin D (r = 0.10) and pack years of smoking (r = 0.11), both P <
      0.01. In the summer months, serum 25-OHD values were higher (55.4 nmol/l) than in
      the winter months (48.1 nmol/l), P < 0.001. The final regression model predicting
      serum 25-OHD levels included race, %TBF and season (all P < 0.05) and explained
      36% of the variance in 25-OHD. CONCLUSIONS: Favourable environmental conditions
      do not result in sufficient vitamin D status for young women, especially non
      Hispanic blacks, Hispanics and the obese.

PMID- 18331610
TI  - Peroxisome proliferator-activated receptor gamma agonism modifies the effects of
      growth hormone on lipolysis and insulin sensitivity.
AB  - CONTEXT: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonists
      such as thiazolidinediones (TZDs) improve insulin sensitivity in type 2 diabetes
      mellitus (T2DM) through effects on fat metabolism whereas GH stimulates lipolysis
      and induces insulin resistance. OBJECTIVE: To evaluate the impact of TZDs on fat
      metabolism and insulin sensitivity in subjects exposed to stable GH levels.
      DESIGN: A randomized, placebo-controlled, double-blind parallel-group study
      including 20 GH-deficient patients on continued GH replacement therapy. The
      patients were studied before and after 12 weeks. INTERVENTION: Patients received
      either pioglitazone 30 mg (N = 10) or placebo (N = 10) once daily for 12 weeks.
      RESULTS: Adiponectin levels almost doubled during pioglitazone treatment (P =
      0.0001). Pioglitazone significantly decreased basal free fatty acid (FFA) levels
      (P = 0.02) and lipid oxidation (P = 0.02). Basal glucose oxidation rate (P =
      0.004) and insulin sensitivity (P = 0.03) improved in the patients who received
      pioglitazone treatment. The change in insulin-stimulated adiponectin level after
      pioglitazone treatment was positively correlated to the change in insulin
      stimulated total glucose disposal (R = 0.69, P = 0.04). CONCLUSION: The impact of
      GH on lipolysis and insulin sensitivity can be modified by administration of
      TZDs.

PMID- 18331612
TI  - Long-term prognosis of medullary thyroid carcinoma.
AB  - OBJECTIVE: The clinical course of patients with medullary thyroid carcinoma (MTC)
      is variable, even in the subgroup of patients after surgery with curative intent
      and postoperatively persistent elevated calcitonin levels. This study aimed to
      evaluate the long-term prognosis of survival in patients with MTC. PATIENTS: Long
      term survival was analysed in 32 patients with MTC being treated in an endocrine
      centre over a 40-year period. Patients were classified as having sporadic MTC,
      familial MTC (FMTC), multiple endocrine neoplasia (MEN) IIA or MEN IIB. RESULTS:
      Seventeen patients had sporadic MTC (53.1%), eight had MEN IIA (25%) and three
      had MEN IIB (9.4%); the remaining four patients (12.5%) had not undergone genetic
      analysis until now. The overall average age at diagnosis was 42.0 years, and the
      median follow-up time was 9.5 years (range 0.5-39 years). Mortality due to
      progressive MTC was 15.6%. The 5-year survival rate was 96% (95% CI 89-100), the
      10-year survival rate 91% (95% CI 79-100), and the 15-year survival rate 85% (95%
      CI 78-100). The estimated mean survival time after initial diagnosis was 31 years
      (95% CI 26.7-37.0). There is a significant difference in survival time between
      patients achieving complete remission compared with patients with biochemical
      persistent disease (P = 0.038) or metastasis (P = 0.0003). In five patients,
      advanced imaging with positron emission tomography/computed tomography (PET/CT)
      identified additional sites of tumour load. Eight more lymph node metastases were
      found in four patients and one local tumour recurrence in one patient by PET/CT.
      CONCLUSION: The overall prognosis of MTC is favourable, even if the rate of
      biochemical cure is lower in MTC than in differentiated types of thyroid cancer.
      This is also true for patients with biochemically persistent disease. Whether the
      identification of further tumour sites by advanced imaging procedures such as
      PET/CT translates into a better prognosis in patients with persistently elevated
      calcitonin levels remains to be investigated.

PMID- 18331611
TI  - Does the RET variant G691S influence the features of sporadic medullary thyroid
      carcinoma?
AB  - OBJECTIVE: The RET (rearranged during transfection) proto-oncogene G691S variant
      is over-represented in the germline of patients with sporadic medullary thyroid
      carcinoma (sMTC) vs. normal controls but so far is not associated with any
      medical or pathological features of the tumour. The aim of our study was to
      assess the influence of this variant on the age of onset, clinical, biological
      and pathological features of sMTC. DESIGN AND PATIENTS: One hundred patients with
      histologically proven MTC, for whom the germline genetic analysis of RET was
      negative and medical records were available, were included in the study. RESULTS:
      Patients with the heterozygous GS variant or the homozygous SS variant (n = 36)
      were on average 8.0 years younger than patients with the wild-type GG variant (n
      = 64, mean age 43.9 vs. 51.9 years, P < 0.01). The former group did not differ
      from the wild-type group in terms of MTC size, prevalence of C-cell hyperplasia
      (CCH) or papillary thyroid carcinoma (PTC). However, the prevalence of an
      increased preoperative basal calcitonin (bCT) level (> 1000 pg/ml) was 2.75-fold
      higher in the patients with the GS or SS variant than in those with the wild-type
      variant (P < 0.001). The proportion of patients with lymph node metastases was
      also higher in the former group (P < 0.05). Multivariate analysis confirmed that
      the presence of the RET variant is independently associated with higher
      preoperative bCT values (P = 0.011). CONCLUSIONS: Our data demonstrate that the
      RET G691S variant could modulate the age of onset of sMTC as demonstrated
      previously for familial tumours. Moreover, this variant is an independent
      predictor of a higher basal calcitonin synthesis rate in patients with sMTC.

PMID- 18331614
TI  - Clinical trial: a randomized controlled cross-over study of flupenthixol +
      melitracen in functional dyspepsia.
AB  - BACKGROUND: Functional dyspepsia is a prevalent condition associated with
      diminished quality of life (QoL) and high economic burden. AIM: To study the
      efficacy of a combination of flupenthixol and melitracen (F + M) with anxiolytic
      and antidepressant properties in functional dyspepsia using a randomized
      controlled cross-over design. METHODS: Patients met the Rome III criteria for
      functional dyspepsia and a validated questionnaire was used to exclude those with
      anxiety or depression. Moreover, patients had to have failed a trial of acid
      suppressive therapy and Helicobacter pylori eradication when positive. End points
      included subjective global symptom relief and QoL assessed by the Nepean
      Dyspepsia Index (NDI). RESULTS: Twenty-five patients (14 females, 11 males; mean
      age = 34.3 +/- 9.9 years) were enrolled and 24 completed the 8-week study. There
      was a significant improvement in subjective global symptom relief with F + M vs.
      placebo (ITT: 73.9% vs. 26.1%, P = 0.001) and a significant drop in the NDI score
      vs. placebo (ITT: -9.0 +/- 11.9 vs. -2.4 +/- 8.9, P = 0.03). No difference was
      noted whether the initial treatment was F + M or placebo. No significant side
      effects were noted. CONCLUSIONS: A combination of F and M is safe and effective
      in the short-term treatment of functional dyspepsia. F + M is associated with
      significant improvement in QoL independent of the presence of anxiety or
      depression.

PMID- 18331613
TI  - The citrulline generation test: proposal for a new enterocyte function test.
AB  - BACKGROUND: The amino acid citrulline is mainly produced by enterocytes from
      conversion of glutamine. As fasting plasma citrulline proved disappointing as a
      biomarker for enterocyte dysfunction in clinical practice, we propose a
      citrulline generation test (CGT) to assess enterocyte function. AIM: To assess
      the feasibility of a CGT in healthy subjects and patients with decreased
      enterocyte mass. METHODS: Nineteen healthy subjects, 16 patients with intestinal
      villous atrophy and nine patients with short bowel syndrome (SBS) were given an
      oral bolus of 20 g of the dipeptide alanine-glutamine. Subsequent changes in
      plasma citrulline and other amino acid concentrations were determined using
      reverse-phase high-performance liquid chromatography. RESULTS: Following the oral
      bolus of alanine-glutamine, plasma citrulline concentrations showed a time
      dependent rise in healthy subjects of 44 +/- 13% (38-55 micromol/L, P < 0.0001).
      The slope from baseline plasma citrulline to peak concentrations was 0.22 +/-
      0.08, 0.13 +/- 0.04 and 0.09 +/- 0.04 micromol/L/min in healthy subjects,
      patients with coeliac disease (CeD) and refractory CeD, respectively (healthy
      subjects vs. CeD P < 0.05, healthy subjects vs. refractory CeD P < 0.001). In
      patients with SBS, the CGT was able to distinguish between non-adapted and
      adapted SBS by means of the incremental area under the CGT curve till 90 min
      (iAUC T90). The iAUC T90 was 447 +/- 179 and 1039 +/- 178 micromol/L/min in non
      adapted and adapted SBS, respectively (P = 0.04). CONCLUSION: An oral bolus of
      alanine-glutamine induces a time-dependent rise in plasma citrulline
      concentration to an extent dependent on the existence of villous atrophy or
      enterocyte hyperplasia in CeD, and adapted SBS, respectively.

PMID- 18331615
TI  - Oxidation as a crucial reaction for cholesterol to induce tissue degeneration:
      CD36 overexpression in human promonocytic cells treated with a biologically
      relevant oxysterol mixture.
AB  - Oxidative stress, inflammation and altered cholesterol metabolism and levels are
      among the pathogenetic mechanisms of cognitive impairment that may accompany
      aging. Within the research area of hypercholesterolemia and age-related disease
      processes, the molecular mechanisms of cholesterol interaction with the
      inflammatory cells of the macrophage lineage are yet to be elucidated. We thus
      investigated the effect of both non-oxidized and oxidized cholesterol on
      monocytic cell differentiation and foam cell formation, as it occurs within
      vascular lesions during progression of atherosclerosis. In vitro experiments
      performed on human U937 promonocytic cells showed that a biologically
      representative mixture of oxysterols markedly stimulated CD36 expression and
      synthesis. In contrast, non-oxidized cholesterol did not exert any effect on CD36
      mRNA and protein levels. Furthermore, the oxysterol-induced up-regulation of CD36
      appeared to be based on the subsequent activation of protein kinase Cdelta
      (PKCdelta), extracellular signal-regulated kinase 1/2 (ERK1/2) and peroxisome
      proliferator-activated receptor gamma (PPARgamma). Cells overexpressing CD36 were
      indeed able to actively take up oxidized low-density lipoproteins, and become
      foam cells. The essential role of ERK pathway and CD36 receptor in oxysterol
      induced foam cell formation was proved by the prevention of the latter event when
      monocytic cells were incubated in the presence of MEK1/2 selective inhibitor or
      anti-CD36 specific antibody. These experimental findings point to cholesterol
      oxidation as an essential reaction for this sterol to exert cellular stress and
      tissue damage in age-related diseases in which inflammation represents a main
      driving force.

PMID- 18331616
TI  - Dietary restriction suppresses proteotoxicity and enhances longevity by an hsf-1
      dependent mechanism in Caenorhabditis elegans.
AB  - Dietary restriction increases lifespan and slows the onset of age-associated
      disease in organisms from yeast to mammals. In humans, several age-related
      diseases are associated with aberrant protein folding or aggregation, including
      neurodegenerative disorders such as Alzheimer's, Parkinson's, and Huntington's
      diseases. We report here that dietary restriction dramatically suppresses age
      associated paralysis in three nematode models of proteotoxicity. Similar to its
      longevity-enhancing properties, dietary restriction protects against
      proteotoxicity by a mechanism distinct from reduced insulin/IGF-1-like signaling.
      Instead, the heat shock transcription factor, hsf-1, is required for enhanced
      thermotolerance, suppression of proteotoxicity, and lifespan extension by dietary
      restriction. These findings demonstrate that dietary restriction confers a
      general protective effect against proteotoxicity and promotes longevity by a
      mechanism involving hsf-1.

PMID- 18331618
TI  - Aging and cancer cell biology, 2008.
AB  - There is increasing support for the idea that aging and cancer are intimately
      connected by the activity of specific genes and the cellular responses to
      potentially oncogenic insults. This Hot Topics review discusses some recently
      published articles that shed light on both the commonalities--and intricacies--of
      the cancer-aging relationship. These articles reveal the expected complexities,
      but also surprising conservation, in mechanisms that link cancer and aging.

PMID- 18331617
TI  - Manganese superoxide dismutase activity regulates transitions between quiescent
      and proliferative growth.
AB  - In recent years, the intracellular reactive oxygen species (ROS) levels have
      gained increasing attention as a critical regulator of cellular proliferation. We
      investigated the hypothesis that manganese superoxide dismutase (MnSOD) activity
      regulates proliferative and quiescent growth by modulating cellular ROS levels.
      Decreasing MnSOD activity favored proliferation in mouse embryonic fibroblasts
      (MEF), while increasing MnSOD activity facilitated proliferating cells'
      transitions into quiescence. MnSOD +/- and -/- MEFs demonstrated increased
      superoxide steady-state levels; these fibroblasts failed to exit from the
      proliferative cycle, and showed increasing cyclin D1 and cyclin B1 protein
      levels. MnSOD +/- MEFs exhibited an increase in the percentage of G(2) cells
      compared to MnSOD +/+ MEFs. Overexpression of MnSOD in MnSOD +/- MEFs suppressed
      superoxide levels and G(2) accumulation, decreased cyclin B1 protein levels, and
      facilitated cells' transit into quiescence. While ROS are known to regulate
      differentiation and cell death pathways, both of which are irreversible
      processes, our results show MnSOD activity and, therefore, mitochondria-derived
      ROS levels regulate cellular proliferation and quiescence, which are reversible
      processes essential to prevent aberrant proliferation and subsequent exhaustion
      of normal cell proliferative capacity. These results support the hypothesis that
      MnSOD activity regulates a mitochondrial 'ROS-switch' favoring a superoxide
      signaling regulating proliferation and a hydrogen peroxide-signaling supporting
      quiescence.

PMID- 18331619
TI  - Increased mechanosensitivity and nuclear stiffness in Hutchinson-Gilford progeria
      cells: effects of farnesyltransferase inhibitors.
AB  - Hutchinson-Gilford progeria syndrome (HGPS), reportedly a model for normal aging,
      is a genetic disorder in children marked by dramatic signs suggestive for
      premature aging. It is usually caused by de novo mutations in the nuclear
      envelope protein lamin A. Lamins are essential to maintaining nuclear integrity,
      and loss of lamin A/C results in increased cellular sensitivity to mechanical
      strain and defective mechanotransduction signaling. Since increased mechanical
      sensitivity in vascular cells could contribute to loss of smooth muscle cells and
      the development of arteriosclerosis--the leading cause of death in HGPS patients-
      we investigated the effect of mechanical stress on cells from HGPS patients. We
      found that skin fibroblasts from HGPS patients developed progressively stiffer
      nuclei with increasing passage number. Importantly, fibroblasts from HGPS
      patients had decreased viability and increased apoptosis under repetitive
      mechanical strain, as well as attenuated wound healing, and these defects
      preceded changes in nuclear stiffness. Treating fibroblasts with
      farnesyltransferase inhibitors restored nuclear stiffness in HGPS cells and
      accelerated the wound healing response in HGPS and healthy control cells by
      increasing the directional persistence of migrating cells. However,
      farnesyltransferase inhibitors did not improve cellular sensitivity to mechanical
      strain. These data suggest that increased mechanical sensitivity in HGPS cells is
      unrelated to changes in nuclear stiffness and that increased biomechanical
      sensitivity could provide a potential mechanism for the progressive loss of
      vascular smooth muscle cells under physiological strain in HGPS patients.

PMID- 18331621
TI  - Prognostic ability of a panel of immunohistochemistry markers - retailoring of an
      'old solution'.
AB  - An urgent requirement exists for new prognostic and predictive assays in breast
      cancer. Despite the development of high-throughput technologies such as DNA
      microarrays, it would now appear that immunohistochemistry (IHC) may play an
      increasingly important role in the clinical management of breast cancer. In this
      editorial, the authors discuss the potential prognostic ability of a panel of IHC
      markers, and question whether this well-established assay technology may in fact
      allow for improved prognostic and predictive tests in breast cancer.

PMID- 18331620
TI  - Proteomic view of mitochondrial function.
AB  - Genomic and proteomic studies have identified hundreds of proteins from
      mitochondria. A recent study has added a functional twist to these systematic
      approaches and identified novel mitochondrial modifiers and regulators.

PMID- 18331622
TI  - Expression and clinical significance of glucose regulated proteins GRP78 (BiP)
      and GRP94 (GP96) in human adenocarcinomas of the esophagus.
AB  - BACKGROUND: Glucose regulated proteins (GRPs) are main regulators of cellular
      homeostasis due to their role as molecular chaperones. Moreover, the functions of
      GRPs suggest that they also may play important roles in cancer biology. In this
      study we investigated the glucose regulated proteins GRP78 (BiP) and GRP94 (GP96)
      in a series of human esophageal adenocarcinomas to determine their implications
      in cancer progression and prognosis. METHODS: Formalin-fixed, paraffin-embedded
      tissues of primary resected esophageal (Barrett) adenocarcinomas (n = 137) and
      corresponding normal tissue were investigated. mRNA-gene expression levels of
      GRP78 and GRP94 were determined by quantitative real-time RT-PCR after mRNA
      extraction. Protein expression analysis was performed with immunohistochemical
      staining of the cases, assembled on a tissue micorarray. The results were
      correlated with pathologic features (pT, pN, G) and overall survival. RESULTS:
      GRP78 and GRP94 mRNA were expressed in all tumors. The relative gene expression
      of GRP78 was significantly higher in early cancers (pT1m and pT1sm) as compared
      to more advanced stages (pT2 and pT3) and normal tissue (p = 0.031). Highly
      differentiated tumors showed also higher GRP78 mRNA levels compared to moderate
      and low differentiated tumors (p = 0.035). In addition, patients with higher
      GRP78 levels tended to show a survival benefit (p = 0.07). GRP94 mRNA-levels
      showed no association to pathological features or clinical outcome.GRP78 and
      GRP94 protein expression was detectable by immunohistochemistry in all tumors.
      There was a significant correlation between a strong GRP78 protein expression and
      early tumor stages (pT1m and pT1sm, p = 0.038). For GRP94 low to moderate protein
      expression was significantly associated with earlier tumor stage (p = 0.001) and
      less lymph node involvement (p = 0.036). Interestingly, the patients with
      combined strong GRP78 and GRP94 protein expression exclusively showed either
      early (pT1m or pT1sm) or advanced (pT3) tumor stages and no pT2 stage (p =
      0.031). CONCLUSION: We could demonstrate an association of GRP78 and GRP94 mRNA
      and protein expression with tumor stage and behaviour in esophageal
      adenocarcinomas. Increased expression of GRP78 may be responsible for controlling
      local tumor growth in early tumor stages, while high expression of GRP78 and
      GRP94 in advanced stages may be dependent from other factors like cellular stress
      reactions due to glucose deprivation, hypoxia or the hosts' immune response.

PMID- 18331623
TI  - Freezing point osmometry of milk to determine the additional water content--an
      issue in general quality control and German food regulation.
AB  - BACKGROUND: The determination of the osmolality of aqueous samples using a
      freezing point osmometer is a well-established, routine laboratory method. In
      addition to their use in clinical and pharmaceutical laboratories, freezing point
      osmometers are also employed in food testing laboratories. One application is the
      determination of the osmolality of milk. Although cow's milk is a natural product
      whose water content is approximately 87%, the osmolality of milk is a significant
      value when the milk is collected from a larger population of animals. This value
      is used in milk processing to control the water content, based on the German Food
      Control Regulations for Milk. RESULTS: Measurement of the freezing point and
      osmolality of milk samples was performed with a Knauer Semi-Micro Freezing Point
      Osmometer. Osmolality was measured for the untreated milk samples and following
      their dilution (by volume) with 10% and 50% water. The measurements were made
      after 1, 4 and 7 days to evaluate changes over time. All measurement values for
      the undiluted milk were spread over a small interval with an average of 271
      mOsmol/kg. After mixing the milk samples with 10% water, the average decreased to
      242 mOsmol/kg, while mixing with 50% water resulted in an average osmolality of
      129 mOsmol/kg. There was no significant change for the osmolality within the 7
      days (measurements from days 1, 4 and 7). CONCLUSION: The results observed
      demonstrate clearly that the additional water content of milk can be determined
      easily using a freezing point osmometer. Milk samples that contain additional
      water have a significantly decreased osmolality, corresponding to an increased
      freezing point. The effect on osmolality of ageing the milk samples could not be
      determined in this study's time-dependent measurements.

PMID- 18331624
TI  - Differentiation of angiogenic burden in human cancer xenografts using a perfusion
      type optical contrast agent (SIDAG).
AB  - INTRODUCTION: Use of fluorescence imaging in oncology is evolving rapidly, and
      nontargeted fluorochromes are currently being investigated for clinical
      application. Here, we investigated whether the degree of tumour angiogenesis can
      be assessed in vivo by planar and tomographic methods using the perfusion-type
      cyanine dye SIDAG (1,1'-bis- [4-sulfobutyl]indotricarbocyanine-5,5'-dicarboxylic
      acid diglucamide monosodium). METHOD: Mice were xenografted with moderately
      (MCF7, DU4475) or highly vascularized (HT1080, MDA-MB435) tumours and scanned up
      to 24 hours after intravenous SIDAG injection using fluorescence reflectance
      imaging. Contrast-to-noise ratio was calculated for all tumours, and fluorochrome
      accumulation was quantified using fluorescence-mediated tomography. The vascular
      volume fraction of the xenografts, serving as a surrogate marker for
      angiogenesis, was measured using magnetic resonance imaging, and blood vessel
      profile (BVP) density and vascular endothelial growth factor expression were
      determined. RESULTS: SIDAG accumulation correlated well with angiogenic burden,
      with maximum contrast to noise ratio for MDA-MB435 (P < 0.0001), followed by
      HT1080, MCF7 and DU4475 tumours. Fluorescence-mediated tomography revealed 4.6
      fold higher fluorochrome concentrations in MDA-MB435 than in DU4475 tumours (229
      +/- 90 nmol/l versus 49 +/- 22 nmol/l; P < 0.05). The vascular volume fraction
      was 4.5-fold (3.58 +/- 0.9% versus 0.8 +/- 0.53%; P < 0.01), blood vessel profile
      density 5-fold (399 +/- 36 BVPs/mm2 versus 78 +/- 16 BVPs/mm2) and vascular
      endothelial growth factor expression 4-fold higher for MDA-MB435 than for DU4475
      tumours. CONCLUSION: Our data suggest that perfusion-type cyanine dyes allow
      assessment of angiogenesis in vivo using planar or tomographic imaging
      technology. They may thus facilitate characterization of solid tumours.

PMID- 18331625
TI  - Detection and identification of NAP-2 as a biomarker in hepatitis B-related
      hepatocellular carcinoma by proteomic approach.
AB  - BACKGROUND: A lack of sensitive and specific biomarkers is a major reason for the
      high rate of Primary hepatocellular carcinoma (HCC)-related mortality. The aim of
      this study was to investigate potential proteomic biomarkers specific for HCC.
      METHODS: 81 patients with hepatitis B-related HCC and 33 healthy controls were
      randomly divided into a training set (33 HCC, 33 controls) and a testing set (48
      HCC, 33 controls). Serum proteomic profiles were measured using Surface-enhanced
      laser desorption/ionization-time-of-flight mass spectroscopy (SELDI-TOF-MS).) A
      classification tree was established by Biomarker Pattern Software (BPS).
      Candidate SELDI peaks were isolated by tricine-SDS-PAGE, identified by HPLC-MS/MS
      and validated by immunohistochemistry (IHC) in liver tissues. RESULTS: A total of
      6 proteomic peaks (3157.33 m/z, 4177.02 m/z, 4284.79 m/z, 4300.80 m/z, 7789.87
      m/z, and 7984.14 m/z) were chosen by BPS to establish a classification tree with
      the highest discriminatory power in the training set. The sensitivity and
      specificity of this classification tree were 95.92%, and 100% respectively in the
      testing set. A candidate marker of about 7984 m/z was isolated and identified as
      neutrophil-activating peptide 2 (NAP-2). IHC staining showed that NAP-2 signals
      were positive in HCC tissues but negative in adjacent tissues. CONCLUSION: The
      NAP-2 may be a specific proteomic biomarker of hepatitis B-related HCC.

PMID- 18331626
TI  - Maternal care in rural China: a case study from Anhui province.
AB  - BACKGROUND: Studies on prenatal care in China have focused on the timing and
      frequency of prenatal care and relatively little information can be found on how
      maternal care has been organized and funded or on the actual content of the
      visits, especially in the less developed rural areas. This study explored
      maternal care in a rural county from Anhui province in terms of care
      organization, provision and utilization. METHODS: A total of 699 mothers of
      infants under one year of age were interviewed with structured questionnaires;
      the county health bureau officials and managers of township hospitals (n = 10)
      and county level hospitals (n = 2) were interviewed; the process of the maternal
      care services was observed by the researchers. In addition, statistics from the
      local government were used. RESULTS: The county level hospitals were well staffed
      and equipped and served as a referral centre for women with a high-risk
      pregnancy. Township hospitals had, on average, 1.7 midwives serving an average
      population of 15,000 people. Only 10-20% of the current costs in county level
      hospitals and township hospitals were funded by the local government, and women
      paid for delivery care. There was no systematic organized prenatal care and
      referrals were not mandatory. About half of the women had their first prenatal
      visit before the 13th gestational week, 36% had fewer than 5 prenatal visits, and
      about 9% had no prenatal visits. A major reason for not having prenatal care
      visits was that women considered it unnecessary. Most women (87%) gave birth in
      public health facilities, and the rest in a private clinic or at home. A total of
      8% of births were delivered by caesarean section. Very few women had any
      postnatal visits. About half of the women received the recommended number of
      prenatal blood pressure and haemoglobin measurements. CONCLUSION: Delivery care
      was better provided than both prenatal and postnatal care in the study area.
      Reliance on user fees gave the hospitals an incentive to put more emphasis on
      revenue generating activities such as delivery care instead of prenatal and
      postnatal care.

PMID- 18331627
TI  - Crucial role of zebrafish prox1 in hypothalamic catecholaminergic neurons
      development.
AB  - BACKGROUND: Prox1, the vertebrate homolog of prospero in Drosophila melanogaster,
      is a divergent homeogene that regulates cell proliferation, fate determination
      and differentiation during vertebrate embryonic development. RESULTS: Here we
      report that, in zebrafish, prox1 is widely expressed in several districts of the
      Central Nervous System (CNS). Specifically, we evidenced prox1 expression in a
      group of neurons, already positive for otp1, located in the hypothalamus at the
      level of the posterior tuberculum (PT). Prox1 knock-down determines the severe
      loss of hypothalamic catecholaminergic (CA) neurons, identified by tyrosine
      hydroxylase (TH) expression, and the synergistic prox1/otp1 overexpression
      induces the appearance of hypothalamic supernumerary TH-positive neurons and
      ectopic TH-positive cells on the yolk epitelium. CONCLUSION: Our findings
      indicate that prox1 activity is crucial for the proper development of the otp1
      positive hypothalamic neuronal precursors to their terminal CA phenotype.

PMID- 18331628
TI  - Computational identification of obligatorily autocatalytic replicators embedded
      in metabolic networks.
AB  - BACKGROUND: If chemical A is necessary for the synthesis of more chemical A, then
      A has the power of replication (such systems are known as autocatalytic systems).
      We provide the first systems-level analysis searching for small-molecular
      autocatalytic components in the metabolisms of diverse organisms, including an
      inferred minimal metabolism. RESULTS: We find that intermediary metabolism is
      invariably autocatalytic for ATP. Furthermore, we provide evidence for the
      existence of additional, organism-specific autocatalytic metabolites in the forms
      of coenzymes (NAD+, coenzyme A, tetrahydrofolate, quinones) and sugars. Although
      the enzymatic reactions of a number of autocatalytic cycles are present in most
      of the studied organisms, they display obligatorily autocatalytic behavior in a
      few networks only, hence demonstrating the need for a systems-level approach to
      identify metabolic replicators embedded in large networks. CONCLUSION: Metabolic
      replicators are apparently common and potentially both universal and ancestral:
      without their presence, kick-starting metabolic networks is impossible, even if
      all enzymes and genes are present in the same cell. Identification of metabolic
      replicators is also important for attempts to create synthetic cells, as some of
      these autocatalytic molecules will presumably be needed to be added to the system
      as, by definition, the system cannot synthesize them without their initial
      presence.

PMID- 18331629
TI  - Malnutrition and bilateral central retinal vein occlusion in a young woman: a
      case report.
AB  - INTRODUCTION: Can vitamin B12 and folate deficiency cause central retinal vein
      occlusion? We conducted a literature search to find out whether nutritional
      deficiency of vitamin B12 and folate can lead to impaired vision. CASE
      PRESENTATION: The patient in the article presented in an eye-casualty department
      in the North East of England with gradual painless visual loss over six weeks.
      She was found to have bilateral central retinal vein occlusion with significant
      anaemia and vitamin B12 and folate deficiency. CONCLUSION: Vitamin B12 and folate
      deficiency can lead to elevated levels of homocysteine. We found a large amount
      of published data relating central retinal vein occlusion to elevated
      homocysteine levels, but there was a lack of conclusive evidence for this
      association Patients should be asked about their dietary history where a
      thrombotic event is suspected or confirmed.

PMID- 18331630
TI  - The burden of disease profile of residents of Nairobi's slums: results from a
      demographic surveillance system.
AB  - BACKGROUND: With increasing urbanization in sub-Saharan Africa and poor economic
      performance, the growth of slums is unavoidable. About 71% of urban residents in
      Kenya live in slums. Slums are characteristically unplanned, underserved by
      social services, and their residents are largely underemployed and poor. Recent
      research shows that the urban poor fare worse than their rural counterparts on
      most health indicators, yet much about the health of the urban poor remains
      unknown. This study aims to quantify the burden of mortality of the residents in
      two Nairobi slums, using a Burden of Disease approach and data generated from a
      Demographic Surveillance System. METHODS: Data from the Nairobi Urban Health and
      Demographic Surveillance System (NUHDSS) collected between January 2003 and
      December 2005 were analysed. Core demographic events in the NUHDSS including
      deaths are updated three times a year; cause of death is ascertained by verbal
      autopsy and cause of death is assigned according to the ICD 10 classification.
      Years of Life Lost due to premature mortality (YLL) were calculated by
      multiplying deaths in each subcategory of sex, age group and cause of death, by
      the Global Burden of Disease standard life expectancy at that age. RESULTS: The
      overall mortality burden per capita was 205 YLL/1,000 person years. Children
      under the age of five years had more than four times the mortality burden of the
      rest of the population, mostly due to pneumonia and diarrhoeal diseases. Among
      the population aged five years and above, HIV/AIDS and tuberculosis accounted for
      about 50% of the mortality burden. CONCLUSION: Slum residents in Nairobi have a
      high mortality burden from preventable and treatable conditions. It is necessary
      to focus on these vulnerable populations since their health outcomes are
      comparable to or even worse than the health outcomes of rural dwellers who are
      often the focus of most interventions.

PMID- 18331631
TI  - Intratracheal dopamine attenuates pulmonary edema and improves survival after
      ventilator-induced lung injury in rats.
AB  - INTRODUCTION: Clearance of alveolar oedema depends on active transport of sodium
      across the alveolar-epithelial barrier. beta-Adrenergic agonists increase
      clearance of pulmonary oedema, but it has not been established whether beta
      agonist stimulation achieves sufficient oedema clearance to improve survival in
      animals. The objective of this study was to determine whether the increased
      pulmonary oedema clearance produced by intratracheal dopamine improves the
      survival of rats after mechanical ventilation with high tidal volume (HVT).
      METHODS: This was a randomized, controlled, experimental study. One hundred and
      thirty-two Wistar-Kyoto rats, weighing 250 to 300 g, were anaesthetized and
      cannulated via endotracheal tube. Pulmonary oedema was induced by endotracheal
      instillation of saline solution and mechanical ventilation with HVT. Two types of
      experiment were carried out. The first was an analysis of pulmonary oedema
      conducted in six groups of 10 rats ventilated with low (8 ml/kg) or high (25
      ml/kg) tidal volume for 30 or 60 minutes with or without intratracheally
      instilled dopamine. At the end of the experiment the animals were exsanguinated
      and pulmonary oedema analysis performed. The second experiment was a survival
      analysis, which was conducted in two groups of 36 animals ventilated with HVT for
      60 minutes with or without intratracheal dopamine; survival of the animals was
      monitored for up to 7 days after extubation. RESULTS: In animals ventilated at
      HVT with or without intratracheal dopamine, oxygen saturation deteriorated over
      time and was significantly higher at 30 minutes than at 60 minutes. After 60
      minutes, a lower wet weight/dry weight ratio was observed in rats ventilated with
      HVT and instilled with dopamine than in rats ventilated with HVT without dopamine
      (3.9 +/- 0.27 versus 4.9 +/- 0.29; P = 0.014). Survival was significantly (P =
      0.013) higher in animals receiving intratracheal dopamine and ventilated with
      HVT, especially at 15 minutes after extubation, when 11 of the 36 animals in the
      HVT group had died as compared with only one out of the 36 animals in the HVT
      plus dopamine group. CONCLUSION: Intratracheal dopamine instillation increased
      pulmonary oedema clearance in rats ventilated with HVT, and this greater
      clearance was associated with improved survival.

PMID- 18331633
TI  - The use of botulinum toxin in head and face medicine: an interdisciplinary field.
AB  - BACKGROUND: In this review article different interdisciplinary relevant
      applications of botulinum toxin type A (BTA) in the head and face region are
      demonstrated. Patients with head and face disorders of different etiology often
      suffer from disorders concerning their musculature (example: synkinesis in mimic
      muscles) or gland-secretion. This leads to many problems and reduces their
      quality of life. The application of BTA can improve movement disorders like
      blepharospasm, hemifacial spasm, synkinesis following defective healing of the
      facial nerve, palatal tremor, severe bruxism, oromandibular dystonias hypertrophy
      of the masseter muscle and disorders of the autonomous nerve system like
      hypersalivation, hyperlacrimation, pathological sweating and intrinsic rhinitis.
      CONCLUSION: The application of botulinum toxin type A is a helpful and minimally
      invasive treatment option to improve the quality of life in patients with head
      and face disorders of different quality and etiology. Side effects are rare.

PMID- 18331632
TI  - Beyond satisfaction: using the Dynamics of Care assessment to better understand
      patients' experiences in care.
AB  - BACKGROUND: Patient perceptions of and satisfaction with care have become
      important indicators of the quality of services and the relationship of services
      to treatment outcomes. However, assessment of these indicators continues to be
      plagued by measurement problems, particularly the lack of variance in
      satisfaction data. In this article, we present a new approach to better capture
      patient perceptions of experiences in care, the Dynamics of Care (DoC)
      assessment. It is an in-depth approach to defining and assessing patients'
      perspectives at different junctures in care, including their decisions about
      whether and where to seek care, the barriers encountered, and the treatments and
      services received. METHODS: The purpose of this article is to describe, validate,
      and discuss the benefits and limitations of the DoC, which was administered as
      part of a longitudinal study to evaluate the New York State HIV Special Needs
      Plan (SNP), a Medicaid managed care model for people living with HIV/AIDS. Data
      are from 426 study respondents across two time points. RESULTS: The results
      demonstrate the validity and value of the DoC. Help seeking decisions and
      satisfaction with care appear to be situation-specific, rather than person
      specific. However, barriers to care appear to be more cross-situational for
      respondents, and may be associated with clients' living situations or care
      arrangements. Inventories in this assessment that were designed to identify
      potential deterrents to help seeking and difficulties encountered in care
      demonstrated clear principal component structures, and helped to explain
      satisfaction with care. The problem resolution index was found to be independent
      from satisfaction with care and the data were more normally distributed. DoC data
      were also associated with subsequent utilization and change in quality of life.
      CONCLUSION: The DoC was designed to be a flexible, integrated measure to
      determine individuals' salient service needs, help seeking and experiences in
      care. One of the many strengths of the assessment is its focus on specific
      problems in context, thus providing a more sensitive and informative way to
      understand processes in care from the patient's perspective. This approach can be
      used to direct new programs and resources to the patients and situations that
      require them.

PMID- 18331634
TI  - Adrenergic gene polymorphisms and cardiovascular risk in the NHLBI-sponsored
      Women's Ischemia Syndrome Evaluation.
AB  - BACKGROUND: Adrenergic gene polymorphisms are associated with cardiovascular and
      metabolic phenotypes. We investigated the influence of adrenergic gene
      polymorphisms on cardiovascular risk in women with suspected myocardial ischemia.
      METHODS: We genotyped 628 women referred for coronary angiography for eight
      polymorphisms in the alpha1A-, beta1-, beta2- and beta3-adrenergic receptors
      (ADRA1A, ADRB1, ADRB2, ADRB3, respectively), and their signaling proteins, G
      protein beta 3 subunit (GNB3) and G-protein alpha subunit (GNAS). We compared the
      incidence of death, myocardial infarction, stroke, or heart failure between
      genotype groups in all women and women without obstructive coronary stenoses.
      RESULTS: After a median of 5.8 years of follow-up, 115 women had an event.
      Patients with the ADRB1 Gly389 polymorphism were at higher risk for the composite
      outcome due to higher rates of myocardial infarction (adjusted hazard ratio [HR]
      3.63, 95% confidence interval [95%CI] 1.17-11.28; Gly/Gly vs. Arg/Arg HR 4.14,
      95%CI 0.88-19.6). The risk associated with ADRB1 Gly389 was limited to those
      without obstructive CAD (n = 400, Pinteraction = 0.03), albeit marginally
      significant in this subset (HR 1.71, 95%CI 0.91-3.19). Additionally, women
      without obstructive CAD carrying the ADRB3 Arg64 variant were at higher risk for
      the composite endpoint (HR 2.10, 95%CI 1.05-4.24) due to subtle increases in risk
      for all of the individual endpoints. No genetic associations were present in
      women with obstructive CAD. CONCLUSION: In this exploratory analysis, common
      coding polymorphisms in the beta1- and beta3-adrenergic receptors increased
      cardiovascular risk in women referred for diagnostic angiography, and could
      improve risk assessment, particularly for women without evidence of obstructive
      CAD. TRIAL REGISTRATION: ClinicalTrials.gov NCT00000554.

PMID- 18331635
TI  - Gene expression analysis of the ovary of hybrid females of Xenopus laevis and X.
      muelleri.
AB  - BACKGROUND: Interspecific hybrids of frogs of the genus Xenopus result in sterile
      hybrid males and fertile hybrid females. Previous work has demonstrated a
      dramatic asymmetrical pattern of misexpression in hybrid males compared to the
      two parental species with relatively few genes misexpressed in comparisons of
      hybrids and the maternal species (X. laevis) and dramatically more genes
      misexpressed in hybrids compared to the paternal species (X. muelleri). In this
      work, we examine the gene expression pattern in hybrid females of X. laevis x X.
      muelleri to determine if this asymmetrical pattern of expression also occurs in
      hybrid females. RESULTS: We find a similar pattern of asymmetry in expression
      compared to males in that there were more genes differentially expressed between
      hybrids and X. muelleri compared to hybrids and X. laevis. We also found a
      dramatic increase in the number of misexpressed genes with hybrid females having
      about 20 times more genes misexpressed in ovaries compared to testes of hybrid
      males and therefore the match between phenotype and expression pattern is not
      supported. CONCLUSION: We discuss these intriguing findings in the context of
      reproductive isolation and suggest that divergence in female expression may be
      involved in sterility of hybrid males due to the inherent sensitivity of
      spermatogenesis as defined by the faster male evolution hypothesis for Haldane's
      rule.

PMID- 18331636
TI  - Transcriptomic analysis of the dialogue between Pseudorabies virus and porcine
      epithelial cells during infection.
AB  - BACKGROUND: Transcriptomic approaches are relevant for studying virus-host cell
      dialogues to better understand the physiopathology of infection and the immune
      response at the cellular level. Pseudorabies virus (PrV), a porcine
      Alphaherpesvirus, is a good model for such studies in pig. Since PrV displays a
      strong tropism for mucous epithelial cells, we developed a kinetics study of PrV
      infection in the porcine PK15 epithelial cell line. To identify as completely as
      possible, viral and cellular genes regulated during infection, we simultaneously
      analyzed PrV and cellular transcriptome modifications using two microarrays i.e.
      a laboratory-made combined SLA/PrV microarray, consisting of probes for all PrV
      genes and for porcine genes contained in the Swine Leukocyte Antigen (SLA)
      complex, and the porcine generic Qiagen-NRSP8 oligonucleotide microarray. We
      confirmed the differential expression of a selected set of genes by qRT-PCR and
      flow cytometry. RESULTS: An increase in the number of differentially expressed
      cellular genes and PrV genes especially from 4 h post-infection (pi) was observed
      concomitantly with the onset of viral progeny while no early global cellular
      shutoff was recorded. Many cellular genes were down-regulated from 4 h pi and
      their number increased until 12 h pi. UL41 transcripts encoding the virion host
      shutoff protein were first detected as differentially expressed at 8 h pi. The
      viral gene UL49.5 encoding a TAP inhibitor protein was differentially expressed
      as soon as 2 h pi, indicating that viral evasion via TAP inhibition may start
      earlier than the cellular gene shutoff. We found that many biological processes
      are altered during PrV infection. Indeed, several genes involved in the SLA class
      I antigenic presentation pathway (SLA-Ia, TAP1, TAP2, PSMB8 and PSMB9), were down
      regulated, thus contributing to viral immune escape from this pathway and other
      genes involved in apoptosis, nucleic acid metabolism, cytoskeleton signaling as
      well as interferon-mediated antiviral response were also modulated during PrV
      infection. CONCLUSION: Our results show that the gene expression of both PrV and
      porcine cells can be analyzed simultaneously with microarrays, providing a
      chronology of PrV gene transcription, which has never been described before, and
      a global picture of transcription with a direct temporal link between viral and
      host gene expression.

PMID- 18331638
TI  - Analysis of oral cancer epidemiology in the US reveals state-specific trends:
      implications for oral cancer prevention.
AB  - BACKGROUND: Downward trends have been observed in oral cancer incidence and
      mortality in the US over the past 30 years; however, these declines are not
      uniform within this population. Several studies have now demonstrated an increase
      in the incidence and mortality from oral cancers among certain demographic
      groups, which may have resulted from increased risks or risk behaviors. This
      study examines the underlying data that comprise these trends, to identify
      specific populations that may be at greater risk for morbidity and mortality from
      oral cancers. METHODS: Oral cancer incidence and mortality data analyzed for this
      study were generated using the National Cancer Institute's Surveillance,
      Epidemiology and End Results (SEER) program. RESULTS: While oral cancer incidence
      and mortality rates have been declining over the past thirty years, these
      declines have reversed in the past five years among some demographic groups,
      including black females and white males. Sorting of these data by state revealed
      that eight states exhibited increasing rates of oral cancer deaths, Nevada, North
      Carolina, Iowa, Ohio, Maine, Idaho, North Dakota, and Wyoming, in stark contrast
      to the national downward trend. Furthermore, a detailed analysis of data from
      these states revealed increasing rates of oral cancer among older white males,
      also contrary to the overall trends observed at the national level. CONCLUSION:
      These results signify that, despite the declining long-term trends in oral cancer
      incidence and mortality nationally, localized geographic areas exist where the
      incidence and mortality from oral cancers have been increasing. These areas
      represent sites where public health education and prevention efforts may be
      focused to target these specific populations in an effort to improve health
      outcomes and reduce disparities within these populations.

PMID- 18331637
TI  - Functionally important segments in proteins dissected using Gene Ontology and
      geometric clustering of peptide fragments.
AB  - We have developed a geometric clustering algorithm using backbone phi,psi angles
      to group conformationally similar peptide fragments of any length. By labeling
      each fragment in the cluster with the level-specific Gene Ontology 'molecular
      function' term of its protein, we are able to compute statistics for molecular
      function-propensity and p-value of individual fragments in the cluster.
      Clustering-cum-statistical analysis for peptide fragments 8 residues in length
      and with only trans peptide bonds shows that molecular function propensities > or
      =20 and p-values < or =0.05 can dissect fragments within a protein linked to the
      molecular function.

PMID- 18331639
TI  - Migration of superior vena cava stent.
AB  - There has been a recent increase in the use of endovascular prostheses resulting
      in complex surgical and interventional complications not previously recognised.
      We report a case of Superior vena cava stenosis treated with a wallstent which
      migrated to the right atrium, necessitating a combined radiological and surgical
      approach to retrieve it.

PMID- 18331640
TI  - Comprehensive analysis of NuMA variation in breast cancer.
AB  - BACKGROUND: A recent genome wide case-control association study identified NuMA
      region on 11q13 as a candidate locus for breast cancer susceptibility.
      Specifically, the variant Ala794Gly was suggested to be associated with increased
      risk of breast cancer. METHODS: In order to evaluate the NuMa gene for breast
      cancer susceptibility, we have here screened the entire coding region and exon
      intron boundaries of NuMa in 92 familial breast cancer patients and constructed
      haplotypes of the identified variants. Five missense variants were further
      screened in 341 breast cancer cases with a positive family history and 368
      controls. We examined the frequency of Ala794Gly in an extensive series of
      familial (n = 910) and unselected (n = 884) breast cancer cases and controls (n =
      906), with a high power to detect the suggested breast cancer risk. We also
      tested if the variant is associated with histopathologic features of breast
      tumors. RESULTS: Screening of NuMA resulted in identification of 11 exonic
      variants and 12 variants in introns or untranslated regions. Five missense
      variants that were further screened in breast cancer cases with a positive family
      history and controls, were each carried on a unique haplotype. None of the
      variants, or the haplotypes represented by them, was associated with breast
      cancer risk although due to low power in this analysis, very low risk alleles may
      go unrecognized. The NuMA Ala794Gly showed no difference in frequency in the
      unselected breast cancer case series or familial case series compared to control
      cases. Furthermore, Ala794Gly did not show any significant association with
      histopathologic characteristics of the tumors, though Ala794Gly was slightly more
      frequent among unselected cases with lymph node involvement. CONCLUSION: Our
      results do not support the role of NuMA variants as breast cancer susceptibility
      alleles.

PMID- 18331641
TI  - Can subtle changes in gene expression be consistently detected with different
      microarray platforms?
AB  - BACKGROUND: The comparability of gene expression data generated with different
      microarray platforms is still a matter of concern. Here we address the
      performance and the overlap in the detection of differentially expressed genes
      for five different microarray platforms in a challenging biological context where
      differences in gene expression are few and subtle. RESULTS: Gene expression
      profiles in the hippocampus of five wild-type and five transgenic deltaC
      doublecortin-like kinase mice were evaluated with five microarray platforms:
      Applied Biosystems, Affymetrix, Agilent, Illumina, LGTC home-spotted arrays.
      Using a fixed false discovery rate of 10% we detected surprising differences
      between the number of differentially expressed genes per platform. Four genes
      were selected by ABI, 130 by Affymetrix, 3,051 by Agilent, 54 by Illumina, and 13
      by LGTC. Two genes were found significantly differentially expressed by all
      platforms and the four genes identified by the ABI platform were found by at
      least three other platforms. Quantitative RT-PCR analysis confirmed 20 out of 28
      of the genes detected by two or more platforms and 8 out of 15 of the genes
      detected by Agilent only. We observed improved correlations between platforms
      when ranking the genes based on the significance level than with a fixed
      statistical cut-off. We demonstrate significant overlap in the affected gene sets
      identified by the different platforms, although biological processes were
      represented by only partially overlapping sets of genes. Aberrances in GABA-ergic
      signalling in the transgenic mice were consistently found by all platforms.
      CONCLUSION: The different microarray platforms give partially complementary views
      on biological processes affected. Our data indicate that when analyzing samples
      with only subtle differences in gene expression the use of two different
      platforms might be more attractive than increasing the number of replicates.
      Commercial two-color platforms seem to have higher power for finding
      differentially expressed genes between groups with small differences in
      expression.

PMID- 18331642
TI  - Treatment of experimental colitis in mice with LMP-420, an inhibitor of TNF
      transcription.
AB  - BACKGROUND: LMP-420 is a boronic acid-containing purine nucleoside analogue that
      transcriptionally inhibits TNF production but is non-cytotoxic to TNF-producing
      cells. METHODS: This study investigated the efficacy of LMP-420 as an anti
      inflammatory agent in acute and chronic colitis induced by oral administration of
      dextran sulfate sodium (DSS) to mice and in chronic colitis following piroxicam
      administration to IL-10-deficient mice. The severity of colon inflammation was
      assessed histologically. TNF levels were measured by enzyme immunoassay. RESULTS:
      Administration of DSS for 7 days resulted in severe acute colitis that was
      associated with a marked increase in stool and colon tissue TNF levels.
      Initiation of therapy with intraperitoneal (i.p.) LMP-420 on day 4 of DSS
      exposure decreased colonic TNF to near normal levels on day 7. However, neither
      i.p. nor oral treatment with LMP-420 affected the development or severity of
      acute DSS colitis. Initiation of LMP-420 therapy after 3 cycles of DSS
      administration to establish chronic colitis also had no effect on the severity of
      chronic colitis. Analysis of colonic TNF combined with longitudinal analysis of
      TNF and TNF receptor (TNF-RII) levels in stool during the development of chronic
      DSS colitis demonstrated that the initially elevated colonic TNF levels returned
      to normal despite intense on-going inflammation in mice with chronic colitis. RAG
      2-/- mice deficient in T and B cells also developed severe ongoing colitis in
      response to 3 cycles of DSS, but showed marked differences vs. wild type mice in
      stool TNF and TNF-RII in response to DSS exposure. Systemic and oral LMP-420
      treatment for 16 days decreased colonic TNF levels in IL-10-deficient mice with
      chronic colitis, with a trend to decreased histologic inflammation for oral LMP
      420. CONCLUSION: These studies demonstrate that short-term treatment with a
      transcriptional inhibitor of TNF production can decrease systemic and local
      colonic levels of TNF but may not decrease the histologic severity of colitis.
      Longer term studies using colitis models that are more dependent on TNF elevation
      should be performed to more accurately assess the potential of LMP-420 for
      therapy of inflammatory bowel disease.

PMID- 18331643
TI  - Correlating corneal arcus with atherosclerosis in familial hypercholesterolemia.
AB  - BACKGROUND: A relationship between corneal arcus and atherosclerosis has long
      been suspected but is controversial. The homozygous familial hypercholesterolemia
      patients in this study present a unique opportunity to assess this issue. They
      have both advanced atherosclerosis and corneal arcus. METHODS: This is a cross
      sectional study of 17 patients homozygous for familial hypercholesterolemia
      presenting to the Clinical Center of the National Institutes of Health. Plasma
      lipoproteins, circumferential extent of arcus, thoracic aorta and coronary
      calcific atherosclerosis score, and Achilles tendon width were measured at the
      National Institutes of Health. RESULTS: Patients with corneal arcus had higher
      scores for calcific atherosclerosis (mean 2865 compared to 412), cholesterol-year
      score (mean 11830 mg-yr/dl compared to 5707 mg-yr/dl), and Achilles tendon width
      (mean 2.54 cm compared to 1.41 cm) than those without. Corneal arcus and Achilles
      tendon width were strongly correlated and predictive of each other. Although
      corneal arcus was correlated with calcific atherosclerosis (r = 0.67; p = 0.004),
      it was not as highly correlated as was the Achilles tendon width (r = 0.855; p <
      0.001). CONCLUSION: Corneal arcus reflects widespread tissue lipid deposition and
      is correlated with both calcific atherosclerosis and xanthomatosis in these
      patients. Patients with more severe arcus tend to have more severe calcific
      atherosclerosis. Corneal arcus is not as good an indicator of calcific
      atherosclerosis as Achilles tendon thickness, but its presence suggests increased
      atherosclerosis in these hypercholesterolemic patients.

PMID- 18331644
TI  - A quantitative method for determining spatial discriminative capacity.
AB  - BACKGROUND: The traditional two-point discrimination (TPD) test, a widely used
      tactile spatial acuity measure, has been criticized as being imprecise because it
      is based on subjective criteria and involves a number of non-spatial cues. The
      results of a recent study showed that as two stimuli were delivered
      simultaneously, vibrotactile amplitude discrimination became worse when the two
      stimuli were positioned relatively close together and was significantly degraded
      when the probes were within a subject's two-point limen. The impairment of
      amplitude discrimination with decreasing inter-probe distance suggested that the
      metric of amplitude discrimination could possibly provide a means of objective
      and quantitative measurement of spatial discrimination capacity. METHODS: A two
      alternative forced-choice (2AFC) tracking procedure was used to assess a
      subject's ability to discriminate the amplitude difference between two stimuli
      positioned at near-adjacent skin sites. Two 25 Hz flutter stimuli, identical
      except for a constant difference in amplitude, were delivered simultaneously to
      the hand dorsum. The stimuli were initially spaced 30 mm apart, and the inter
      stimulus distance was modified on a trial-by-trial basis based on the subject's
      performance of discriminating the stimulus with higher intensity. The experiment
      was repeated via sequential, rather than simultaneous, delivery of the same
      vibrotactile stimuli. RESULTS: Results obtained from this study showed that the
      performance of the amplitude discrimination task was significantly degraded when
      the stimuli were delivered simultaneously and were near a subject's two-point
      limen. In contrast, subjects were able to correctly discriminate between the
      amplitudes of the two stimuli when they were sequentially delivered at all inter
      probe distances (including those within the two-point limen), and improved when
      an adapting stimulus was delivered prior to simultaneously delivered stimuli.
      CONCLUSION: Subjects' capacity to discriminate the amplitude difference between
      two vibrotactile stimulations was degraded as the inter-stimulus distance
      approached the limit of their two-point spatial discriminative capacity. This
      degradation of spatial discriminative capacity lessened when an adapting stimulus
      was used. Performance of the task, as well as improvement on the task with
      adaptation, would most likely be impaired if the cortical information processing
      capacity of a subject or subject population were systemically altered, and thus,
      the methods described could be effective measures for use in clinical or clinical
      research applications.

PMID- 18331645
TI  - Psychological drivers in doping: the life-cycle model of performance enhancement.
AB  - BACKGROUND: Performance enhancement (PE) is a natural and essential ingredient of
      competitive sport. Except for nutritional supplement contamination, accidental
      use of doping is highly unlikely. It requires deliberation, planning and
      commitment; and is influenced by a host of protective and risk factors.
      HYPOTHESIS: In the course of their career, athletes constantly set goals and make
      choices regarding the way these goals can be achieved. The cycle of choice - goal
      commitment - execution - feedback on goal attainment - goal evaluation/adjustment
      has numerous exit points, each providing an opportunity for behaviour change,
      which may or may not be related to the use of prohibited methods. The interplay
      between facilitating and inhibiting systemic and personality factors, constantly
      influenced by situational factors could result in an outcome vector of 'doping
      attitudes', which combines with subjective norms to influence intentions to
      choose prohibited PE methods. These influences also vary from one stage of
      athlete development to the next, making some athletes more vulnerable to engaging
      in doping practices than others, and more vulnerable at certain time periods -
      and not others. TESTING THE HYPOTHESIS: Model-testing requires a series of
      carefully planned and coordinated studies. Correlational studies can establish
      relationships where the directionality is not-known or not important.
      Experimental studies with the manipulation of doping expectancies and risk
      factors can be used to demonstrate causality and evaluate potential intervention
      strategies. The final model can be tested via a behavioural simulation, with
      outcomes compared to those expected from literature precedence or used as a
      simulated computer game for empirical data collection. IMPLICATIONS: A
      hypothesized life-cycle model of PE identifies vulnerability factors across the
      stages of athlete development with the view of informing the design of anti
      doping assessment and intervention. The model suggests that, instead of focusing
      on the actual engagement in prohibited PE practices, deterrence strategies are
      likely to be more effective if they target the influencing factors at the
      appropriate stage and identify groups of athletes and their respective career
      stages, which pose particular risks of engagement in doping practices. This
      enables a more effective intervention approach by targeting specific risk factors
      and expectancies.

PMID- 18331647
TI  - Analyzing stochastic transcription to elucidate the nucleoid's organization.
AB  - BACKGROUND: The processes of gene transcription, translation, as well as the
      reactions taking place between gene products, are subject to stochastic
      fluctuations. These stochastic events are being increasingly examined as it
      emerges that they can be crucial in the cell's survival. In a previous study we
      had examined the transcription patterns of two bacterial species (Escherichia
      coli and Bacillus subtilis) to elucidate the nucleoid's organization. The basic
      idea is that genes that share transcription patterns, must share some sort of
      spatial relationship, even if they are not close to each other on the chromosome.
      We had found that picking any gene at random, its transcription will be
      correlated with genes at well-defined short - as well as long-range distances,
      leaving the explanation of the latter an open question. In this paper we study
      the transcription correlations when the only transcription taking place is
      stochastic, in other words, no active or "deterministic" transcription takes
      place. To this purpose we use transcription data of Sinorhizobium meliloti.
      RESULTS: Even when only stochastic transcription takes place, the co-expression
      of genes varies as a function of the distance between genes: we observe again the
      short-range as well as the regular, long-range correlation patterns. CONCLUSION:
      We explain these latter with a model based on the physical constraints acting on
      the DNA, forcing it into a conformation of groups of a few successive large and
      transcribed loops, which are evenly spaced along the chromosome and separated by
      small, non-transcribed loops. We discuss the question about the link between
      shared transcription patterns and physiological relationship and come to the
      conclusion that when genes are distantly placed along the chromosome, the
      transcription correlation does not imply a physiological relationship.

PMID- 18331646
TI  - The involvement of Bax in zinc-induced mitochondrial apoptogenesis in malignant
      prostate cells.
AB  - BACKGROUND: The development and progression of prostate cancer requires the
      transformation of normal zinc-accumulating epithelial cells to malignant cells
      that have lost the ability to accumulate zinc. This metabolic transformation is
      essential so that the tumor suppressive effects of zinc can be eliminated and the
      malignant process can proceed. One of the major effects of zinc is its prevention
      of prostate cell growth by its induction of apoptosis. The accumulation of
      cellular zinc has a direct effect on the mitochondria that results in the release
      of cytochrome c, which initiates the caspase cascade that leads to apoptosis.
      This effect is associated with the mitochondrial pore-forming process, but the
      mechanism by which zinc induces the release of cytochrome c and induces
      mitochondrial apoptogenesis has not been resolved. The present report provides
      for the first time information that implicates Bax in the zinc induction of
      mitochondrial apoptogenesis. RESULTS: The effects of zinc treatment on the Bax
      levels of PC-3 cells and on the mitochondria were determined. The exposure of
      isolated mitochondria to zinc results in an increase in membrane bound Bax, which
      is due to the mitochondrial insertion of endogenous resident Bax. The
      mitochondrial Bax/Bcl-2 ratio is increased by zinc treatment. Zinc treatment of
      PC-3 cells also increases the mitochondrial level of Bax. In addition, zinc
      treatment increases the cellular level of Bax and the cellular Bax/Bcl2 ratio.
      Down regulation of Bax in PC-3 cells eliminates the zinc induction of apoptosis.
      The increase in cellular Bax level appears to involve zinc induction of Bax gene
      expression. CONCLUSION: This report extends and confirms that physiological
      levels of zinc induce apoptosis in prostate cells. The study provides evidence
      that zinc is directly involved in facilitating a Bax-associated pore formation
      process that initiates mitochondrial apoptogenesis. This is enhanced by an
      additional effect of zinc on increasing the cellular level of Bax. To avoid the
      anti-tumor apoptogenic effects of zinc, the malignant cells in prostate cancer
      posses genetic/metabolic adaptations that prevent the cellular accumulation of
      zinc.

PMID- 18331648
TI  - Salmon louse (Lepeophtheirus salmonis) transcriptomes during post molting
      maturation and egg production, revealed using EST-sequencing and microarray
      analysis.
AB  - BACKGROUND: Lepeophtheirus salmonis is an ectoparasitic copepod feeding on skin,
      mucus and blood from salmonid hosts. Initial analysis of EST sequences from pre
      adult and adult stages of L. salmonis revealed a large proportion of novel
      transcripts. In order to link unknown transcripts to biological functions we have
      combined EST sequencing and microarray analysis to characterize female salmon
      louse transcriptomes during post molting maturation and egg production. RESULTS:
      EST sequence analysis shows that 43% of the ESTs have no significant hits in
      GenBank. Sequenced ESTs assembled into 556 contigs and 1614 singletons and
      whenever homologous genes were identified no clear correlation with homologous
      genes from any specific animal group was evident. Sequence comparison of 27 L.
      salmonis proteins with homologous proteins in humans, zebrafish, insects and
      crustaceans revealed an almost identical sequence identity with all species.
      Microarray analysis of maturing female adult salmon lice revealed two major
      transcription patterns; up-regulation during the final molting followed by down
      regulation and female specific up regulation during post molting growth and egg
      production. For a third minor group of ESTs transcription decreased during
      molting from pre-adult II to immature adults. Genes regulated during molting
      typically gave hits with cuticula proteins whilst transcripts up regulated during
      post molting growth were female specific, including two vitellogenins.
      CONCLUSION: The copepod L.salmonis contains high a level of novel genes. Among
      analyzed L.salmonis proteins, sequence identities with homologous proteins in
      crustaceans are no higher than to homologous proteins in humans. Three distinct
      processes, molting, post molting growth and egg production correlate with
      transcriptional regulation of three groups of transcripts; two including genes
      related to growth, one including genes related to egg production. The function of
      the regulated transcripts is discussed in relation to post molting morphological
      changes in adult female salmon louse. There is clear evidence that transcription
      of the major yolk proteins is not induced before some of the post molting growth
      of abdomen and the genital segment has occurred. A hallmark for the observed
      growth is transcription of many putative cuticula proteins prior to the size
      increase.

PMID- 18331649
TI  - Two mosaic terminal inverted duplications arising post-zygotically: Evidence for
      possible formation of neo-telomeres.
AB  - OBJECTIVE: To elucidate the structure of terminal inverted duplications and to
      investigate potential mechanisms of formation in two cases where there was
      mosaicism with cells of apparently normal karyotype. RESULTS: A karyotype
      [46,XY,inv dup(4)(p16.3p15.1)/46,XY] performed on blood lymphocytes from a
      patient referred for developmental delay (case 1) demonstrated a normal karyotype
      in 60% of cells with a terminal inverted duplication 4p in the remainder. In case
      2, referred for multiple fetal anomalies on an ultrasound scan, 33% of amniocyte
      colonies were karyotypically normal, with a terminal inv dup 10p in the remainder
      [46,XX,inv dup(10)(p15.3p11)/46,XX]. Duplicated FISH signals for GATA3 and NEBL
      loci (in case 2), and for the Wolf-Hirschhorn locus (case 1) confirmed the
      inverted structure of both duplications. In the GTL banded normal cells from both
      cases, there was a cryptic deletion detected by FISH of one copy of the
      subtelomere 4p (case 1, probe GS-36P21), and subtelomere 10p (case 2, probe GS
      306F7). At pter on both inv dup chromosomes there was no FISH signal present for
      the specific subtelomere probe. However, a positive pantelomeric probe signal was
      detected at 4 pter and 10 pter in both the cryptically-deleted chromosomes and
      the inv dup chromosomes in the respective cell lines of both cases. CONCLUSION:
      An inv dup structure was evident for both cases on GTL bands, and confirmed by
      the various FISH studies. The presence of telomere (TTAGGG repeat) sequences at
      pter on the inv dup chromosomes (where more proximal chromosome specific
      subtelomeric probes were negative) was indicated by the pantelomeric probe
      signals in both cases. We conclude the most likely mechanism of origin in both
      cases was by sub-telomeric breakage in the zygote at pter, and delayed
      repair/rearrangement until after one or more subsequent mitotic divisions. In
      these divisions, at least one breakage-fusion-bridge cycle occurred, to produce
      inverted duplications. It is proposed then that two differently "repaired"
      daughter cells proliferated in parallel. In one daughter cell line (with an
      overtly normal karyotype) there was deletion of the subtelomere and presumed
      repair through capping by a neo-telomere (i.e. "healing", as initially proposed
      by McClintock). This occurred in both cases presented. In the other daughter cell
      of each case, it is proposed that chromosome stabilization was achieved (after
      replication) by sister chromatid reunion to form a dicentric, which broke at a
      subsequent anaphase, to form an inverted duplication (with loss of the reciprocal
      product, and the other daughter cell line). One inv dup was repaired without an
      interstitial specific subtelomere (case 1) and one was repaired with a duplicated
      specific interstitial subtelomere (case 2). After repair TTAGGG repeats were
      detected by FISH at each respective new pter.

PMID- 18331650
TI  - Obsessive compulsive disorder comorbidity in DBA.
AB  - Diamond-Blackfan Anemia (DBA) is a congenital erythroid aplasia characterized as
      a normochromic macrocytic anemia with a selective deficiency in red blood cell
      precursors in otherwise normocelullar bone marrow. DBA is known to be associated
      with mental retardation and learning disabilities. Although comorbidities with
      other psychiatric conditions have not been reported in the existing literature,
      we report in this paper a case of a DBA patient with previously undiagnosed
      comorbidity of obsessive compulsive disorder (OCD), successfully treated with
      sertaline 200 mg/day and valproic acid 600 mg/day. This case of comorbid
      presentation has clinical, therapeutic and pathophysiological implications. Given
      the difficulty of distinguishing among mental retardation, learning disabilities
      and OCD and the importance of precocious diagnosis in treating OCD especially
      since there are treatment methods interfering with anemia symptoms, physicians
      should adapt an adequate screening tool treating a child with DBA and comorbid
      mental disorder.

PMID- 18331651
TI  - Exploring evidence-policy linkages in health research plans: a case study from
      six countries.
AB  - The complex evidence-policy interface in low and middle income country settings
      is receiving increasing attention. Future Health Systems (FHS): Innovations for
      Equity, is a research consortium conducting health systems explorations in six
      Asian and African countries: Bangladesh, India, China, Afghanistan, Uganda, and
      Nigeria. The cross-country research consortium provides a unique opportunity to
      explore the research-policy interface. Three key activities were undertaken
      during the initial phase of this five-year project. First, key considerations in
      strengthening evidence-policy linkages in health system research were developed
      by FHS researchers through workshops and electronic communications. Four key
      considerations in strengthening evidence-policy linkages are postulated:
      development context; research characteristics; decision-making processes; and
      stakeholder engagement. Second, these four considerations were applied to
      research proposals in each of the six countries to highlight features in the
      research plans that potentially strengthen the research-policy interface and
      opportunities for improvement. Finally, the utility of the approach for setting
      research priorities in health policy and systems research was reflected upon.
      These three activities yielded interesting findings. First, developmental
      consideration with four dimensions - poverty, vulnerabilities, capabilities, and
      health shocks - provides an entry point in examining research-policy interfaces
      in the six settings. Second, research plans focused upon on the ground realities
      in specific countries strengthens the interface. Third, focusing on research
      prioritized by decision-makers, within a politicized health arena, enhances
      chances of research influencing action. Lastly, early and continued engagement of
      multiple stakeholders, from local to national levels, is conducive to enhanced
      communication at the interface. The approach described has four main utilities:
      first, systematic analyses of research proposals using key considerations ensure
      such issues are incorporated into research proposals; second, the exact meaning,
      significance, and inter-relatedness of these considerations can be explored
      within the research itself; third, cross-country learning can be enhanced; and
      finally, translation of evidence into action may be facilitated. Health systems
      research proposals in low and middle income countries should include reflection
      on transferring research findings into policy. Such deliberations may be informed
      by employing the four key considerations suggested in this paper in analyzing
      research proposals.

PMID- 18331652
TI  - Quality of life in children three and nine months after discharge from a
      paediatric intensive care unit: a prospective cohort study.
AB  - BACKGROUND: Improved survival in children with critical illnesses has led to new
      disease patterns. As a consequence evaluation of the well being of survivors of
      Pediatric Intensive Care Units (PICU) has become important. Outcome assessment
      should therefore consist of evaluation of morbidity, functional health and Health
      Related Quality of Life (HRQoL). Awareness of HRQoL consequences and physical
      sequelae could lead to changes in support during the acute phase and thereafter.
      The aim of this study was to evaluate HRQoL in PICU survivors. METHODS:
      Prospective follow-up study three and nine months after discharge from a 14-bed
      tertiary PICU. Eighty-one of 142 eligible, previously healthy children were
      included from December 2002 through October 2005. HRQoL was assessed with the TNO
      AZL Preschool Children Quality of Life Questionnaire (TAPQOL-PF) for children
      aged 1 to 6 years of age, the TNO-AZL Children's Quality of Life Questionnaire
      Parent Form (TACQOL-PF) for children aged 6 to 12 years of age, and the TNO-AZL
      Children's Quality of Life Questionnaire Child Form (TACQOL-CF) for children aged
      8 to 15 years of age. The studied patients were compared with age appropriate
      normative data using non-parametric tests and effect sizes. RESULTS: Thirty-one
      and 27 children, and 55 and 50 parents completed questionnaires respectively
      three and nine months after discharge. In 1-6 year old children parents reported
      more lung problems (3 and 9 months), worse liveliness (9 months) and better
      appetite and problem behaviour (3 months); in 6-12 year old children parents
      reported worse motor functioning (3 months); and 12-15 year old adolescents
      reported worse motor functioning (3 months). Large effect sizes indicating
      clinical significant differences in HRQoL with healthy control subjects were
      found on more domains. CONCLUSION: In this small group of PICU survivors
      differences in HRQoL with the normative population exist three and nine months
      after discharge. Calculated effect sizes were smaller nine months after
      discharge. These changes suggest that HRQoL improves over time. More research is
      necessary but we believe that HRQoL assessment should be incorporated in follow
      up programs of PICU survivors.

PMID- 18331653
TI  - Effects of prenatal exposure to diesel exhaust particles on postnatal
      development, behavior, genotoxicity and inflammation in mice.
AB  - BACKGROUND: Results from epidemiological studies indicate that particulate air
      pollution constitutes a hazard for human health. Recent studies suggest that
      diesel exhaust possesses endocrine activity and therefore may affect reproductive
      outcome. This study in mice aimed to investigate whether exposure to diesel
      exhaust particles (DEP; NIST 2975) would affect gestation, postnatal development,
      activity, learning and memory, and biomarkers of transplacental toxicity.
      Pregnant mice (C57BL/6; BomTac) were exposed to 19 mg/m3 DEP (~1.106
      particles/cm3; mass median diameter congruent with 240 nm) on gestational days 9
      19, for 1 h/day. RESULTS: Gestational parameters were similar in control and
      diesel groups. Shortly after birth, body weights of DEP offspring were slightly
      lower than in controls. This difference increased during lactation, so by weaning
      the DEP exposed offspring weighed significantly less than the control progeny.
      Only slight effects of exposure were observed on cognitive function in female DEP
      offspring and on biomarkers of exposure to particles or genotoxic substances.
      CONCLUSION: In utero exposure to DEP decreased weight gain during lactation.
      Cognitive function and levels of biomarkers of exposure to particles or to
      genotoxic substances were generally similar in exposed and control offspring. The
      particle size and chemical composition of the DEP and differences in exposure
      methods (fresh, whole exhaust versus aged, resuspended DEP) may play a
      significant role on the biological effects observed in this compared to other
      studies.

PMID- 18331655
TI  - Laryngeal chondritis induced by C3-4 osteophyte following supracricoid
      laryngectomy with cricohyoidoepiglottopexy: report of two cases.
AB  - OBJECTIVES: We have performed supracricoid laryngectomy with
      cricohyoidoepiglottopexy or with cricohyoidopexy for tumour (T) stage T2 and T3
      laryngeal cancer cases and some T4 cases. We report the clinical symptoms and
      management, using this technique to avoid complications. CASE REPORT: Among
      patients undergoing the procedure, two cases manifested laryngeal chondritis
      following laryngectomy with cricohyoidoepiglottopexy. This complication was
      caused by C3-4 cervical osteophytes physically contacting the cricoid cartilage.
      Laryngeal microlaryngoscopy was performed, which revealed white, necrotic tissue
      in the posterior wall of the pharynx and persistent oedema of the neoglottis.
      CONCLUSIONS: When encountering a patient with an excessive osteophyte formation
      at the level of C3-4, one needs to take extra precautions when undertaking
      laryngectomy with cricohyoidoepiglottopexy or with cricohyoidopexy.

PMID- 18331654
TI  - Primary tracheal tumours: 21 years of experience at Peking Union Medical College,
      Beijing, China.
AB  - OBJECTIVES: To review our experience of the treatment of primary tracheal
      tumours. STUDY DESIGN: All medical notes of patients with primary tracheal
      tumours diagnosed between 1981 and 2002 were retrospectively analysed. RESULTS:
      In this period, 80 patients were diagnosed with primary tracheal malignancy, 48
      males and 32 females. The median age was 48 years. Sixty-nine patients had
      malignant tumours, most commonly adenoid cystic carcinoma (50.7 per cent) or
      squamous cell carcinoma (30.4 per cent). Fifty-five patients underwent surgery,
      30 of whom also received radiotherapy. Twenty-five patients received only
      radiotherapy. The five-year survival rate for all malignant tumours was 30.5 per
      cent. The five-year survival rates for adenoid cystic carcinoma and squamous cell
      carcinoma were 40.2 and 24.6 per cent, respectively. Local recurrence and distant
      metastases developed in 21 patients (30.4 per cent). CONCLUSION: Primary tracheal
      tumours are rare and mainly malignant. Surgery is the most effective treatment
      method. Technical advances allow for safe resection of the tumour with a safe,
      tension-free anastomosis.

PMID- 18331656
TI  - Use of complementary and alternative medicine by patients attending a head and
      neck oncology clinic.
AB  - INTRODUCTION: Within the United Kingdom, there are 50,000 practitioners of
      complementary and alternative medicine, with five million people consulting these
      practitioners yearly. The aim of this study was to explore the use of such
      therapies by patients attending a head and neck oncology clinic in Aberdeen.
      METHOD: Questionnaires were distributed to 200 patients over an eight-week
      period. The questionnaire consisted of questions regarding: demographic factors;
      48 listed herbal preparations and alternative therapies; reasons for their use;
      and opinions on their efficacy. RESULTS: One hundred and thirty-eight patients
      completed the questionnaires. Fifty per cent (69/138) of respondents had used
      complementary and alternative medicine previously, with 26 per cent having used
      it in the preceding year. Fifty-five per cent of respondents learned about
      complementary and alternative medicine use from friends, and the majority
      obtained such medicines by purchasing from a shop. Fifty per cent (34/69) of
      respondents stated that their family physician was unaware of their use of
      complementary and alternative medicine. CONCLUSION: All medical practitioners
      should be aware of increasing complementary and alternative medicine usage by the
      United Kingdom population, and should be able to counsel patients appropriately.

PMID- 18331657
TI  - Embolisation of an extensive arteriovenous malformation of the temporal region as
      an alternate treatment: case report.
AB  - OBJECTIVES: To report the case of a spontaneous arteriovenous malformation
      involving the auricula, external auditory meatus, middle ear and part of the
      petrous apex, and also to provide updated information about its management. CASE
      REPORT: A 33-year-old woman presented complaining of accelerated growth of a
      retro-auricular swelling during her latest pregnancy, together with pain,
      pulsatile tinnitus and ear discharge. An arteriovenous malformation occupying the
      right auricula, external auditory canal, mastoid process of the temporal bone and
      the lateral half of the petrous segment was diagnosed, using temporal
      computerised tomography and magnetic resonance imaging. The lesion was embolised
      with polyvinyl alcohol particles at angiography. Excision of the arteriovenous
      malformation nidus was performed. Three years post-operatively, magnetic
      resonance imaging showed no residual lesion or recurrence at the temporal bone
      and petrous apex, although a few scanty, serpiginous, vascular remnants had
      persisted. CONCLUSIONS: In the head and neck, arteriovenous malformations usually
      occur intracranially; they are rare outside the cranium. To our knowledge, there
      have been no previously published cases of such an extensive arteriovenous
      malformation involving the temporal region. Apropos of our case, the definition,
      clinical findings, diagnostic approaches and therapeutic management of
      arteriovenous malformations are discussed.

PMID- 18331658
TI  - Foreign body reaction to polymethylsiloxane gel (Bioplastique) after vocal fold
      augmentation.
AB  - STATEMENT OF PROBLEM: The consequences of vocal fold paralysis include voice
      change, airway problems and difficulty swallowing. Medialisation procedures using
      injected material have been used for many decades, with varying outcomes, mainly
      secondary to lifespan, tissue reaction or migration. Newer materials have
      recently become clinically available which are easier to manage and supposedly
      less likely to elicit foreign body reaction. METHOD OF STUDY: Case report.
      RESULTS: We report a case of foreign body reaction and possible migration of
      polymethylsiloxane gel (Bioplastique), one such material, after vocal fold
      injection. To our knowledge, this is the second such case described. CONCLUSIONS:
      This case highlights the fact that the risk of foreign body reaction and
      migration is still present for this material, albeit low. We also highlight the
      fact that, although this material can cause foreign body reactions and may
      possibly migrate, it is removable by microlaryngoscopy via the microflap
      technique, with vocal improvement.

PMID- 18331659
TI  - Predictors of response to short-term proton pump inhibitor treatment in
      laryngopharyngeal reflux patients.
AB  - OBJECTIVES: To assess benefit from one and three months' empirical proton pump
      inhibitor treatment in patients with suspected laryngopharyngeal reflux, and to
      define pre-therapy factors which may predict success with short-term proton pump
      inhibitor treatment. STUDY DESIGN: Prospective, open clinical study. MATERIALS
      AND METHODS: One hundred adult out-patients with suspected laryngopharyngeal
      reflux were enrolled in the study. Laryngopharyngeal reflux patients underwent
      endoscopy and received omeprazole for three months. Efficacy of treatment was
      assessed at one and three months. Patients were classified as responders if their
      total symptom score had improved at least 50 per cent, their videolaryngoscopic
      score had improved by at least two points, and they were satisfied with the
      results. Pre-therapy factors assessed for an effect on omeprazole outcomes
      included: patient demographics, reflux symptoms, videolaryngoscopic scores,
      endoscopic findings, overall vocal dysfunction degree, self-rated voice handicap
      index, hospital anxiety and depression scale scores, and general well-being
      score. RESULTS: Fifty-six per cent of patients were classified as responders at
      one month of treatment; this proportion rose to 92 per cent at three months.
      Those patients entering the study with a higher heartburn score showed a
      significant response after one month of omeprazole treatment. Non-responders were
      found to have significantly more anxiety than responders. Logistic regression
      analysis revealed these factors, plus the medication dose, as being relevant for
      faster response prediction. No significant association was found between pre
      therapy factors and three-month response to proton pump inhibitor treatment.
      CONCLUSION: Three months of proton pump inhibitor treatment twice daily is
      warranted for confirming suspicion of laryngopharyngeal reflux. Baseline anxiety
      levels and heartburn scores, and the medication dose, may be relevant factors
      when predicting faster response to proton pump inhibitor treatment in carefully
      selected patients.

PMID- 18331660
TI  - Another reason for intra-operative imaging during cochlear implantation.
AB  - OBJECTIVE: We report a case of a rare cochlear implant complication: the
      introduction of the electrode array into the superior semicircular canal, with
      intra-operative measurements of neural response reactions suggesting reasonable
      functioning of the implant. CASE REPORT: A two-year old patient affected by
      congenital, profound, sensorineural deafness underwent bilateral cochlear
      implantation at the ENT clinic of the 'La Sapienza' University of Rome. Two
      Clarion 90k devices were implanted, and electrophysiological and radiological
      checks were performed. After the introduction of the array in the right side,
      neural response imaging was performed, and a neural potential was found only on
      two apical electrodes, at a stimulation intensity of 431 clinical units. The
      situation differed on the left side, where neural response imaging was present at
      a stimulation intensity of 300 clinical units on the two electrodes tested (one
      apical electrode (number three), and one middle electrode (number nine)). Intra
      operative radiological assessment with a transorbital plain films was performed
      as usual in order to assess the position of the electrodes inside the cochlea.
      This radiography showed the electrode array to be in the superior semicircular
      canal in the right ear. CONCLUSION: Intra-operative monitoring tests during
      cochlear implant surgery play different roles; measurement of impedances and
      neural response imaging can evaluate the integrity of implant electrodes and the
      status of the electrode-cochlea interface, but it must not be the sole way in
      which correct positioning of the array is confirmed. In our opinion, intra
      operative radiological assessment is mandatory during cochlear implant surgery.

PMID- 18331661
TI  - Superior semicircular canal dehiscence syndrome: a new aetiology.
AB  - OBJECTIVE: We report what we believe to be a unique aetiology of the superior
      semicircular canal dehiscence syndrome, a recently described condition in which
      vestibular imbalance and/or hearing loss results from the loss of continuity of
      the bone overlying the superior semicircular canals. CASE REPORT: A 58-year-old
      woman presented with autophony in the right ear and momentary imbalance when
      shouting (Tullio phenomenon). Temporal bone computed tomography revealed a defect
      of the right superior semicircular canal caused by an enlarged superior petrosal
      sinus receiving drainage from a large cerebellar developmental venous anomaly.
      CONCLUSIONS: We review superior semicircular canal dehiscence syndrome and its
      management, and we discuss common aetiologies, contrasting these with the unusual
      aetiology presented here. We conclude that superior semicircular canal dehiscence
      syndrome may present with a solely developmental aetiology, despite presenting
      late in life.

PMID- 18331662
TI  - The nutraceutical role of the Phaseolus vulgaris alpha-amylase inhibitor.
AB  - The present review assesses the potential of the Phaseolus vulgaris alpha-amylase
      inhibitor isoform 1 (alpha-AI1) starch blockers as a widely used remedy against
      obesity and diabetes. Consumption of the alpha-amylase inhibitor causes marginal
      intraluminal alpha-amylase activity facilitated by the inhibitor's appropriate
      structural, physico-chemical and functional properties. As a result there is
      decreased postprandial plasma hyperglycaemia and insulin levels, increased
      resistance of starch to digestion and increased activity of colorectal bacteria.
      The efficacy and safety of the amylase inhibitor extracts, however, depend on the
      processing and extraction techniques used. The extracts are potential ingredients
      in foods for increased carbohydrate tolerance in diabetics, decreased energy
      intake for reducing obesity and for increased resistant starch. Research
      developments in the distribution and biosynthesis of the alpha-amylase inhibitor,
      relevant physico-chemical properties, the molecular starch-blocking mechanism,
      anti-obesity and anti-diabetes effects, safety of extracts and the need for
      research into their potential anti-colorectal cancer effect are discussed.

PMID- 18331663
TI  - Assessing caffeine exposure in pregnant women.
AB  - Studies on the effects of caffeine on health, while numerous, have produced
      inconsistent results. One of the most uncertain and controversial effects is on
      pregnancy outcome. Studies have produced conflicting results due to a number of
      methodological variations. The major challenge is the accurate assessment of
      caffeine intake. The aim of the present study was to explore different methods of
      assessing caffeine exposure in pregnant women. Twenty-four healthy pregnant women
      from the UK city of Leeds completed both a detailed questionnaire, the caffeine
      assessment tool (CAT) designed specifically to assess caffeine intake and a
      prospective 3 d food and drink diary. The women also provided nine saliva samples
      over two consecutive days for estimation of caffeine and a metabolite
      (paraxanthine). Caffeine intakes from the CAT and diary showed adequate agreement
      (intra-class correlation coefficient of 0.5). For saliva caffeine and
      paraxanthine measures, the between-sample variation (within the same woman) was
      greater than between-woman and between-day variation. However, there was still
      adequate agreement between these measures and the CAT. The CAT is a valuable tool
      that is now being used in a large prospective study investigating caffeine's role
      in pregnancy outcome.

PMID- 18331664
TI  - Dietary fibre and fermentability characteristics of root crops and legumes.
AB  - The dietary fibre and fermentability characteristics of local root crops and
      legumes were determined. Total, soluble and insoluble fibre were determined in
      six root crops (kamote, gabi, potato, tugi, ube, cassava) and ten legumes
      (mungbean, soyabean, peanut, pole sitao, cowpea, chickpea, green pea, lima bean,
      kidney bean and pigeon pea) using Association of Official Analytical Chemists
      methods. The dietary fibre from test foods was isolated and fermented in vitro
      using human faecal inoculum simulating conditions in the human colon. The SCFA,
      e.g. acetate, propionate, butyrate, produced after fibre fermentation was
      measured using HPLC. The dietary fibre content of root crops ranged from 4.6 to
      13.5 g/100 g while legumes ranged from 20.9 to 46.9 g/100 g, suggesting that root
      crops and legumes are good sources of dietary fibre. Significant amounts of SCFA
      were produced after in vitro fermentation of the fibre isolate of both root crops
      and legumes. The best sources (as mmol/g fibre isolate) of acetate among the
      legumes were pole sitao (5.6 (sem 0.5)) and mungbean (5.3 (sem 0.1)) and among
      the root crops, tugi (2.5 (sem 0.4)) and cassava (2.4 (sem 0.1)); of propionate,
      kidney bean (7.2 (sem 1.5)) and pigeon pea (3.3 (sem 0.2)) for legumes, and tugi
      (1.8 (sem 0.2)) for root crops; and of butyrate, peanut (6.0 (sem 0.2)) and
      cowpea (5.4 (sem 0.2)) for legumes, and tugi (0.8 (sem 0.0)) and cassava (0.8
      (sem 0.0)) for root crops. In conclusion, root crops and legumes are good sources
      of dietary fibre and produced SCFA after fibre fermentation, such as acetate,
      propionate and butyrate. SCFA production after in vitro fermentation can be
      estimated using human faecal inoculum and can be used to model the human colon.

PMID- 18331665
TI  - Socio-economic status and handedness in two large cohorts of French adults.
AB  - Left-and right-handers have coexisted since the Palaeolithic age. Hand preference
      is heritable. Moreover, there is extensive evidence of an association between
      left-handedness and several fitness costs. In this context, the persistence of
      the polymorphism is interesting. Here, we explore the associations between socio
      economic status and handedness, analysing data from two large cohorts of adult
      men and women. Such associations are relevant to an evolutionary approach, as the
      socio-economic and the reproductive value are related. Our results partly support
      the hypothesis that left-handers have a socio-economic status advantage,
      countervailing the health issues. Although the models explain a small proportion
      of the variance observed, the frequency of left-handedness is significantly
      higher: (1) among women of higher educational level; (2) among categories of
      higher income; and (3) among individuals who have a higher position in the
      company. The importance of these findings for the evolution of the polymorphism
      of handedness is discussed.

PMID- 18331666
TI  - Power and Type I errors for pairwise comparisons of means in the unequal
      variances case.
AB  - A Monte Carlo simulation was conducted to compare pairwise multiple comparison
      procedures. The number of means varied from 4 to 8 and the sample sizes varied
      from 2 to 500. Procedures were evaluated on the basis of Type I errors, any-pair
      power and all-pairs power. Two modifications of the Games and Howell procedure
      were shown to make it conservative. No procedure was found to be uniformly most
      powerful. For any pair power the Games and Howell procedure was found to be
      generally most powerful even when applied at more stringent levels to control
      Type I errors. For all pairs power the Peritz procedure applied with modified
      Brown-Forsythe tests was found to be most powerful in most conditions.

PMID- 18331667
TI  - Using the common sense model to design interventions for the prevention and
      management of chronic illness threats: from description to process.
AB  - In this article, we discuss how one might use the common sense model of self
      regulation (CSM) for developing interventions for improving chronic illness
      management. We argue that features of that CSM such as its dynamic, self
      regulative (feedback) control feature and its system structure provide an
      important basis for patient-centered interventions. We describe two separate,
      ongoing interventions with patients with diabetes and asthma to demonstrate the
      adaptability of the CSM. Finally, we discuss three additional factors that need
      to be addressed before planning and implementing interventions: (1) the use of
      top-down versus bottom-up intervention strategies; (2) health care interventions
      involving multidisciplinary teams; and (3) fidelity of implementation for
      tailored interventions.

PMID- 18331668
TI  - Anemia in chronic obstructive pulmonary disease: epidemiology and economic
      implications.
AB  - BACKGROUND: Anemia in chronic illness is associated with increased healthcare
      resource utilization (HRU) and costs. In COPD, it occurs frequently and
      influences both clinical and economic outcomes. Because no data studies have been
      performed either in a single center or a subpopulation of COPD patients, anemia's
      influence on the outcomes is not fully understood. RESEARCH DESIGN AND METHODS:
      We conducted a retrospective cohort study in a large healthcare database to
      quantify prevalence, HRU and costs of anemia in COPD. From 1997 to 2005, patients
      > or = 45 years of age with an ICD-9 diagnosis code for COPD and > 3.5 years of
      follow-up were included. Anemia was defined by the WHO criteria. Other disease
      states for which anemia is a known complication were excluded. We calculated the
      prevalence of anemia and compared annual HRU and costs between COPD patients with
      and without anemia. Multiple regression analysis adjusted for the effects of age,
      gender, race, length of enrollment, diagnosing physician specialty, co-morbidity
      burden, anemia and COPD severity. RESULTS: Of the 2404 patients with COPD, 33% (n
      = 788) had a diagnosis of anemia. Anemic patients were older, more likely to be
      male and non-Caucasian, and had a greater co-morbidity burden than non-anemic
      individuals. Annual costs for COPD patients with anemia were more than twice
      those for patients without anemia ($17,240 vs. 6492, p < 0.001, unadjusted). HRU
      was also significantly greater among anemic than non-anemic COPD patients (p <
      0.0001). In a multiple regression analysis, anemia accounted for $7929 per
      patient (95% CI: $5572-10,599) of the total costs of care. LIMITATIONS: This is a
      retrospective cohort study and thus subject to multiple forms of bias. Although
      spirometric evidence of COPD was available only for a subgroup of patients, our
      case identification methods have been previously validated and found to be
      accurate in recognizing COPD. CONCLUSIONS: Anemia is a common co-morbidity in
      COPD. It is significantly associated with an increase in HRU and costs of care
      for COPD, independent of demographic and clinical patient characteristics.

PMID- 18331669
TI  - A Markov cost-utility analysis of escitalopram and duloxetine for the treatment
      of major depressive disorder.
AB  - OBJECTIVE: To estimate the costs and quality-adjusted life weeks of duloxetine
      and escitalopram. RESEARCH DESIGN: A probabilistic Markov cost-utility analysis
      with a time horizon of 1 year using data from placebo controlled randomized
      clinical trials for both products. METHODS: Efficacy was defined as remission of
      depressive symptoms and converted to utilities. Side effects were incorporated
      using rates from clinical trials and converted to utilities to define treatment
      effectiveness. The effectiveness outcome was quality adjusted life weeks (QALWs).
      Estimates of effectiveness (efficacy and side effects) used beta distributions
      and costs used gamma distributions. Using a managed care perspective, medication
      costs and physician office visits were included in the model, along with costs
      associated with treatment failure. Antidepressant costs were obtained using
      average wholesale price minus 20%. Physician visit costs were obtained from the
      2006 US Medicare fee schedule for physician services. A Monte Carlo simulation
      was conducted using 1000 trials with both first- and second-order sampling.
      RESULTS: Over 1 year, the estimated mean quality-adjusted life weeks was 41.0
      (95% confidence interval [CI]: 40.7-41.3) for escitalopram and 38.2 (95% CI: 37.9
      38.4) for duloxetine. The mean annual total medical cost for escitalopram was
      $907 (95% CI: $894-$919) and $1633 (95% CI: $1614-$1654) for duloxetine.
      Limitations to this analysis include using separate studies examining the
      efficacy and adverse events of either escitalopram or duloxetine, assuming the
      switch, augmentation, and titration rates for duloxetine to be similar to
      escitalopram, and using utility estimates from published literature for the
      antidepressant adverse events. CONCLUSION: This analysis suggests that
      escitalopram was more effective in terms of QALWs and less costly than duloxetine
      for treatment of depression.

PMID- 18331670
TI  - [Problems and countermeasures in orbital plastic and reconstructive surgery].
AB  - The great progress in orbital plastic and reconstructive surgery (OPRS) in China
      has been reached since the 21st century. However, obvious disparities exist
      between China and the developed countries in terms of the insufficiency of
      quality and quantity of surgeons of OPRS, lack of standardized and systematic
      training in China. It is necessary to pay attention to the diagnosis, prevention
      and treatment of orbital deformities, master surgical techniques and selection of
      the right moment of OPRS, study on orbital repairing materials and tissue
      engineering bone. Other important measures to improve the level of OPRS in China
      would include considering the characteristic of OPRS, establishing standardized
      and systematic professional trainings for orbital plastic surgeon, and
      strengthening basic and clinical research in OPRS.

PMID- 18331671
TI  - [Choice of proper time for orbital implant in anophthalmia children].
AB  - From birth to adulthood, craniofacial development is dependent on the normal
      orbital growth. The increase of orbital volume is related to the growth of
      eyeball. Debates are ongoing as to when should be the appropriate age to remove
      abnormal globes and place orbital implants before puberty. Some articles
      suggested that the earlier to place of orbital implants the better, however, some
      considered that static orbital implants make invalid for stimulating the bony
      orbit to a full-developed volume, which will result in more than once
      implantation procedures. This article will focus on the growth of the orbit and
      the eyeball, retard of orbital development caused by soft tissue absence, as well
      as the selection of proper time for the placement of orbital implants during
      childhood.

PMID- 18331672
TI  - [Use of periocular superficial musculo-aponeurotic system flap and hard palate
      mucosal graft in reconstruction of full-thickness eyelid defects].
AB  - OBJECTIVE: To investigate the outcome of combining grafting of periocular
      superficial musculo-aponeurotic system (SMAS) flaps and hard palate mucosa in the
      reconstruction of modest and severe full-thickness eyelid defects. METHODS: Hard
      palate mucosa was grafted to replace the posterior layers of the eyelid (the
      tarsus and the conjunctiva) while periocular SMAS flap, which is rich in blood
      supply, was utilized to reconstruct the anterior layers of the eyelid (the skin
      and muscular layer). Among the 26 eyes of 26 patients treated with full-thickness
      eyelid defects of half or more palpebral length, orbicularis muscular flaps were
      utilized in 5 cases, superficial temporal arterial flaps in 5 cases, supra
      eyebrow flaps in 7 cases and upper eyelid skin-orbicularis bipedicled flaps in 9
      cases. The operation began with the grafting of hard palate mucosa. Periocular
      SMAS flaps were then designed according to the location and scope of the defect
      of the anterior layers of the eyelids and transposition procedure ensued. After
      the grafting procedures, tarsorrhaphy was performed in all cases and the closure
      was maintained for 3 months. RESULTS: All patients were followed for 6 to 36
      months, averaged 11 months. The flaps and hard palate mucosal grafts existed well
      in all cases. No shrinkage in hard palate mucosal grafts was observed and
      satisfactory aesthetic and functional results were achieved. CONCLUSIONS:
      Combining grafting of periocular SMAS flap and hard palate mucosa can repair full
      thickness eyelid defects as a one-stage operation with definite and good outcome.

PMID- 18331673
TI  - [Clinical characteristics of moderate and severe Marcus-Gunn jaw-winking
      synkinesis and its surgical treatment].
AB  - OBJECTIVE: To investigate the clinical characteristics of moderate and severe
      Marcus-Gunn jaw winking synkinesis and it surgical management. METHODS: Thirty
      three patients with Marcus-Gunn syndrome were enrolled from 1997 to 2003 in
      Zhongshan Ophthalmic Center. The clinical characteristics were analyzed based on
      the records. Unilateral levator excision and frontalis flap suspension were
      performed for the correction of ptosis and the results were analyzed. RESULTS:
      The follow-up period varied from 1 to 6 years. Sixteen patients were male and 17
      were female. The left eye was involved in 22 patients and the right eye in 11
      patients. There was no family history. The amount of ptosis in each patient was
      more than 2 mm. At the end of observation, good results were achieved for ptosis
      correction in 26 (87%) of 30 patients, fair results in 3 (10%) patients.
      CONCLUSIONS: The ptosis of patients with moderate and severe Marcus-Gunn syndrome
      needs to be treated surgically. Unilateral frontalis flap suspension combined
      levator excision can correct ptosis very well for patients with moderate and
      severe Marcus-Gunn syndrome.

PMID- 18331674
TI  - [Obstruction of lacrimal pathways in naso-orbital-ethmoid fractures and the
      relationship between lacrimal obstruction and fracture types].
AB  - OBJECTIVE: To analyze the incidence and pattern of lacrimal pathways obstruction
      after naso-orbital-ethmoid fractures (NOE), and to investigate the relationship
      between lacrimal obstruction and fracture types. METHODS: One hundred and one
      patients with NOE fractures were analyzed retrospectively. These patients were
      treated in the Department of Ophthalmology, Ninth People's Hospital, Medical
      School of Shanghai Jiao Tong University from January 2000 to January 2005. The
      fractures were grouped in according to the classification of Markowitz. All of
      the patients were assessed with syringing and probing or dacryocystography. The
      incidence of obstruction in different NOE fracture types was analyzed to
      illustrate the relationship between obstructions and fracture types. The
      incidence of different obstruction parts of lacrimal system was evaluated to find
      which part was more vulnerable. RESULTS: In 101 NOE cases, 63 cases were
      accompanied with lacrimal obstruction. The naso-lacrimal system was more
      vulnerable in its bony canal than in the lacrimal canalicular. Obstruction was
      found in the bony nasolacrimal canal in 39 patients (61.90%), and in the lacrimal
      canaliculus in 12 patients (19.48%). The defect of lacrimal sacs was found in 7
      cases (11.11%), and lacrimal punctum was lost in 5 cases (7.94%). Three patterns
      of fracture were defined according to the Markowitz classification. Sixteen
      patients were classified into type I; 37 into type II; 48 into type III according
      to the Markowitz standard. The incidence of obstructions were 25% in type INOE
      fracture, 54.05%% in type II, 81.25% in type III, respectively. CONCLUSIONS: NOE
      fracture can cause lacrimal obstruction. Naso-lacrimal obstruction is the most
      common type. The incidence of obstruction changes with the severity of injury and
      the pattern of fracture.

PMID- 18331675
TI  - [Effect of porous polyethylene channel implants on volume reconstruction of large
      orbital wall fractures evaluated by computed tomography measurement].
AB  - OBJECTIVE: To assess the clinical effectiveness of porous polyethylene medpor
      channel implants (MCI) to restore orbital volume in repairing orbital wall
      fractures, evaluated by computed tomography (CT) and volume measurement program.
      METHODS: Sixteen patients with unilateral large orbital fractures were included
      in this study. Computed tomography (CT) scans were used to obtain computer-based
      orbital volume measurement to assess the change in orbital volume pre- and post
      operatively. Pre- and post-operative enophthalmos were measured using a Hertel
      exophthalmometer. The average time interval between injury and surgery was
      (17.4+/-10.0) days, and the mean follow-up period was 9 months. RESULTS:
      Postoperative CT scan showed that most of the MCI to be well positioned. The
      orbital volume of the injured orbit was significantly increased [mean: (28.16+/
      4.32) cm3] as compared with unaffected orbit preoperatively (t=3.044, P<0.01).
      There was no statistical difference in orbital volume between the injured and
      normal orbits after orbital reconstruction (t=0.069, P>0.05). The orbital volume
      change after reconstructive surgery was significantly positively correlated with
      the decrease of enophthalmos (r=0.715, P<0.01). In order to resolve 2 mm
      enophthalmos, more than 2.86 cm3 orbital volume augmentation is recommended.
      CONCLUSIONS: Orbital volume measurement by CT scan is useful in the post
      traumatic evaluation of severity of orbital fractures, and it can help predict
      the degree of late enophthalmos. Orbital reconstruction with the MCI, when
      indicated, is recommended.

PMID- 18331676
TI  - [Early clinical study of bimanual microphacoemulsification with rollable
      intraocular lens].
AB  - OBJECTIVE: To analyze the results of bimanual microphacoemulsification combined
      with rollable intraocular lens (IOL), to evaluate the feasibility and safety of
      this procedure and to compare the clinical results of two different types of
      rollable intraocular lens. METHODS: Thirty-five cases (35 eyes) were divided into
      2 groups. Group 1 included 15 eyes used Thinoptx IOL, Group 2 included 20 eyes
      used Acri. Smart IOL. The data included best corrected visual acuity (BCVA) and
      intraocular pressure (IOP) (pre-, 1 day, 1 week and 1 month post-operatively);
      corneal curvature (pre- and 1 month post-operatively); target refraction and post
      operation refraction (1 month after the operation). RESULTS: A significant
      difference was found between pre-operative and 1 month post-operative BCVA
      (P<0.01). No significant different was found between pre-operative and post
      operative IOP, astigmatism, target refraction and refraction. There was no
      significant difference in pre-operative and post-operative astigmatism, target
      refraction and post-operation 1-month refraction between these two groups.
      CONCLUSIONS: Bimanual microphacoemulsification with rollable intraocular lens
      (IOL) is a feasible and safe procedure for the cataract surgery.

PMID- 18331677
TI  - [Photodynamic therapy for circumscribed choroidal hemangioma].
AB  - OBJECTIVE: To investigate the safety and efficacy of photodynamic therapy in
      patients with circumscribed choroidal haemangioma (CCH). METHODS: Five patients
      diagnosed as CCH according to ophthalmoscopy, fundus fluorescein angiography and
      coloured doppler imaging were treated by photodynamic therapy using verteporfin.
      Four of them were accompanied by serous retinal detachment extending into the
      macula. The range of the best-corrected visual acuity was 0.02-0.8, and the
      thickness of the angioma ranged from 2.5 to 5.4 mm while the base dimension was
      between 6.5-12.5 mm. The patients were followed up for 13 weeks to 56 weeks after
      photodynamic therapy. RESULTS: The serous retinal detachments resolved completely
      and the visual acuity either improved or remained stable in all cases after once
      PDT, The final best-corrected visual acuity ranged from 0.2 to 0.9. CONCLUSIONS:
      PDT is effective in the management of CCH, and especially safe for the treatment
      of macular choroidal haemangioma. PDT can make the tumor regressed and the visual
      acuity preserved or improved.

PMID- 18331678
TI  - [Clinical features of Best vitelliform macular dystrophy].
AB  - OBJECTIVE: To investigate the clinical features of Best vitelliform macular
      dystrophy (BVMD) in Chinese patients. METHODS: Ten consecutive patients (20 eyes)
      were diagnosed as BVMD by the fundus photography, EOG, fluorescein angiography
      (FFA) and optical coherence tomography (OCT). Their clinical data were analyzed
      retrospectively. RESULTS: Of the twenty eyes from ten patients, three eyes from
      three patients (age range 9-18 years, mean 12.33+/-4.93 years) in Stage II, two
      eyes from two patients (age range 9-18, mean 13.50+/-6.36 years) in Stage IIa,
      four eyes from two patients (age range 11-29 years, mean 20.00+/-10.39 years) in
      Stage III and eleven from six patients (age range 9-44 years, mean 27.09+/-14.02
      years) in Stage IV were found at their first presentation to our hospital. OCT
      scan showed the broadening of the outer-retina-choroid-complex signal with the
      retinal elevation in Stage II. The moderately reflective material which
      represents the vitelliform material may accumulate forming a conical mound that
      would elevate the retinal sensory layer in Stage IIa. In 'pseudohypopon' or
      atrophy phase there may be a large volume of serous retinal detachment. If a
      fibrous macular or foveal atrophy was seen in the fundus photograph, the thinning
      of the outer-retina-choroid-complex signal with serous retinal detachment may be
      shown by OCT. CONCLUSIONS: The present observation is a first study on the
      clinical findings of Chinese BVMD patients. It supports the hypothesis that the
      yellowish material is located under the RPE. Long term evaluation with more
      patients should be done to acknowledge more characteristics of BVMD in Chinese
      patients.

PMID- 18331679
TI  - [Diagnosis and treatment of ciliary epithelium tear combined with retinal
      detachment].
AB  - OBJECTIVE: To analyze the clinical characteristics and treatment of the ciliary
      epithelium tear combined with retina detachment of the eye, and consequently, to
      reduce mistaken and missed diagnosis and to improve the cure rate. METHODS: The
      clinical data, treatment, and follow up results of 17 eyes from 16 cases of
      ciliary epithelium tear combined with retina detachment were analyzed
      retrospectively. RESULTS: All of the patients had a history of eye trauma. All
      eyes showed ciliary epithelium tear combined with retina detachment by the fundus
      examination. All eyes were treated with sclera buckling and cryotherapy.
      Subretinal fluid draining was applied in 13 eyes and combined pneumatic
      retinopexy was performed in 4 eyes. The detached retina was reattached in all
      eyes and visual acuity was improved during the follow up period. CONCLUSIONS:
      Ciliary epithelium tear combined with retina detachment always appears after eye
      injury. The super nasal quadrant is the most frequently affected region. The use
      of ultrasound biomicroscopy, gonioscopy and binocular indirect ophthalmoscopy
      combined with sclera pressure technique helps to obtain a correct diagnosis.
      Sclera buckling surgery results in a high success rate.

PMID- 18331680
TI  - [Retinotopic representations of human visual cortex revealed by functional
      magnetic resonance imaging].
AB  - OBJECTIVE: To establish a set of methodological standard of retinotopic mapping
      using functional magnetic resonance imaging (MRI), to discuss anatomical features
      of functionally delineated V1/V2 boundary based on retinotopic criteria. METHODS:
      Three adults aged 25-30 (1 male and 2 females), right-handed, without
      contraindications of MRI were studied. Visual acuity was 20/20 or corrected to
      20/20. Visual stimuli subtended a field of view of approximately 12 degrees,
      consisted of high contrast, achromatic and drifting checkerboards. Two types of
      stimuli were used: the rotating wedge, either clockwise or counterclockwise, to
      map the polar angle and the annular ring, either contracting or expanding, to map
      eccentricity. MRI parameters: GE signa VH/i 3.0T scanner. Functional data: GRE
      EPI sequence, 20 slices lay perpendicular to the calcarine sulcus, TR: 2 s, TE:
      40 ms, FA: 90 degrees, Phase: 128, FOV: 19 cm, matrix: 64x64, slice: 3 mm, gap:
      0, resolution: 2.9 mmx2.9 mmx3.0 mm. Anatomical data was obtained using 3D-SPGR
      sequence to acquire high resolution. Data was analyzed using AFNI. In order to
      avoid the disadvantages of restricted view due to highly convoluted occipital
      cortex, cortical surface was unfolded and then cut and flattened. Functional data
      was presented to this flattened surface and subsequently analyzed. RESULTS: By
      using the phase-encoded visual stimuli, retinotopic organizations were exactly
      revealed both in the eccentricity and polar angle dimensions. Eccentricity maps
      showed that foveal representation lay in the occipital poles and the
      representation appeared further anterior as eccentricity increased. Polar angle
      maps showed that early retinotopically organized areas had either a mirror or non
      mirror image representation of visual field. Boundaries of different visual areas
      were manually delineated based on retinotopic criteria called visual field sign,
      and the functionally delineated V1/V2 boundary located on the crests of gyrus.
      CONCLUSIONS: Phase-encoded stimuli is validated to be an efficient way to reveal
      retinotopic representation of visual cortex, promising a solid foundation for the
      future research under pathological conditions. Anatomical features of
      functionally delineated V1/V2 boundary support the wiring optimization principle.

PMID- 18331681
TI  - [Etiological analysis on bacterial endophthalmitis].
AB  - OBJECTIVE: To investigate the spectrum of organisms causing bacterial
      endophthalmitis and their sensitivities to commonly used ocular antibiotics.
      METHODS: A retrospective analysis on microbiological records of 728 intraocular
      specimens of patients with suspected endophthalmitis from January 1999 to
      December 2006. Antibiotic susceptibility of these isolates was determined for
      commonly used ocular antibiotics using the Kirby-Bauer disk-diffusion test.
      RESULTS: In all, 168 organisms were isolated from 728 intraocular specimens
      during the study interval. Overall, 96 (57.1%) of 168 isolates were Gram-positive
      cocci, 52 (31.0%) were Gram-negative bacilli, 18 (10.7%) were Gram-positive
      bacilli, and 2 (1.2%) were Gram-negative cocci. The most common organisms
      identified were Staphylococcus epidermidis in 21.4% (36/168), Staphylococcus
      aureus in 11.3% (19/168), and Pseudomonas aeruginosa in 8.9% (15/168). For Gram
      positive cocci, sensitivities were the following: vancomycin 93.4% (85/91),
      levofloxacin 84.4% (81/96), ofloxacin 68.8% (66/96), ciprofloxacin 59.4% (57/96),
      gentamicin 56.3% (54/96), and tobramycin 43.8% (42/96). For Gram-negative
      bacilli, sensitivities were the following: levofloxacin 88.2% (45/51), ofloxacin
      76.9% (40/52), ciprofloxacin 75.0% (39/52), gentamicin 49.0% (25/51), and
      tobramycin 48.1% (25/52). Comparing the data from 2003 to 2006 with the data from
      1999 to 2002, the susceptibility of organisms to frequently employed antibiotics
      was decreasing. CONCLUSIONS: The spectrum of organisms causing bacterial
      endophthalmitis is complex, and no single antibiotic provided coverage for all of
      the microbes isolated from intraocular specimens with bacterial endophthalmitis.
      Combination therapy is recommended as the initial empiric treatment of suspected
      bacterial endophthalmitis.

PMID- 18331682
TI  - [Expression of dopamine receptor D2 and adenosine receptor A2A in human retinal
      pigment epithelium].
AB  - OBJECTIVE: The aim of this study was to identify the presence of dopamine
      receptor D2 and adenosine receptor A2A in human retinal pigment epithelium (RPE)
      in order to determine whether the RPE is a potential site of action for these two
      receptors. METHODS: RPE Cells were isolated and cultured. Reverse transcription
      polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to
      detect the expression of D2 and A2A receptors in the RPE. RESULTS: RT-PCR
      analysis showed that mRNA of D2 and A2A receptors were expressed in the RPE. D2
      and A2A receptors were distributed in the RPE by immunocytochemistry.
      CONCLUSIONS: This study demonstrated the presence of D2 and A2A receptors in
      human RPE at both mRNA and protein levels. D2 and A2A receptors may play an
      important role in the maintenance of the function of human retinal pigment
      epithelium. Furthermore, their cooperation appeared to be important in the
      development of axial myopia and retinal and choroidal neovascularization.

PMID- 18331683
TI  - [CD4+CD25+ T cells involved in induction of rat corneal allograft immune
      tolerance].
AB  - OBJECTIVE: To explore the expression of CD4+CD25+ regulatory T cells in corneal
      graft, in the iris and peripheral blood in the high risk rat corneal transplant
      tolerance induced by superantigen staphylococcal enterotoxin B (SEB). METHODS: A
      high risk rat penetrating corneal transplantation model was established, whereas
      SD rat donor corneas were implanted into Wistar rat recipients. The recipient
      rats were divided into two groups. Group control and group SEB had
      intraperitoneal injection of normal saline solution or SEB (75 microg/kg),
      respectively. Orthotopic corneal transplantation was performed 1 day after the
      injection. The corneal graft survival time was evaluated. The expression of
      CD4+CD25+ T cells in corneal grafts and the iris was evaluated by
      immunohistochemical staining. The percentage of CD4+CD25+ regulatory T cells in
      peripheral blood was determined by flow cytometry. RESULTS: Corneal graft mean
      survival time was (11.63+/-2.83) d in group control and (14.13+/-0.99) d in group
      SEB. The difference of survival time between these two groups was statistically
      significant (P<0.05). Histopathology showed remarkable inflammatory cells
      infiltration in the rejected grafts. The intensity of the infiltration was
      compatible with the severity of rejection reaction. Immunohistochemical staining
      of grafts showed that the CD4+CD25+ regulatory T cells were expressed in rejected
      grafts in both groups 20 days after the surgery, but not before the surgery. The
      iris whole mount staining showed that before the surgery, no expression of
      CD4+CD25+ regulatory T cells was observed in group control but relatively
      remarkable expression was observed in group SEB. Twenty days after the
      transplantation, CD4+CD25+ regulatory T cells were observed in both groups while
      group SEB had more pronounced expression. Peripheral blood flow cytometry
      analysis revealed that the mean percentages of CD4+CD25+ regulatory T cells were
      stable before and after surgery in group control. However, in group SEB, an
      increase shift appeared and followed by a decrease to normal level 20 d after the
      surgery. CONCLUSION: CD4+CD25+ regulatory T cells take part in immune tolerance
      in rat immune tolerance induced by superantigen SEB in high risk rat corneal
      transplantation.

PMID- 18331684
TI  - [Effect of pyruvate on polyol pathway and lens epithelium apoptosis in diabetic
      rats].
AB  - OBJECTIVE: To investigate the effect of polyol pathway on the lens epithelium
      apoptosis and caspase-3 activity and its reversal by pyruvate in diabetic rats.
      METHODS: Two hundred and twenty Wistar rats were divided into 3 groups: control
      group (60 rats), experiment group (80 rats) and treatment group (80 rats). After
      streptozotocin (STZ) induced cataract, the treatment group received 2% pyruvate
      in the diet and drinking. Lens opacification was detected by microscope every 2
      weeks. Amounts of glucose and sorbitol in the lens were quantified by high
      performance liquid chromatography 4, 8 and 12 weeks after the treatment. The
      percentage of lens epithelium undergoing apoptosis was measured by Annexin V-PI
      staining. The activity of caspase-3 was analyzed by Western-blot. RESULTS:
      Present study showed that there was significant increase of glucose and sorbitol
      in the lens in the experiment group, the apoptosis rate and caspase-3 activity of
      lens epithelium were also gradually increased. Pyruvate treatment decreased the
      levels of sorbitol, glucose, lens epithelium apoptosis and caspase-3 activity.
      The progress of cataract was also significantly delayed. CONCLUSIONS: Activation
      of polyol pathway, possibly through regulation of the activity of caspase-3, can
      induce apoptosis of the lens epithelium. Pyruvate ingested orally can effectively
      inhibit diabetic cataractogenesis in rats through inhibit polyol pathway.

PMID- 18331685
TI  - [Insulin-like growth factor-1 induced activation and expression of signal
      transducers and activators of transcription-3 in scleral fibroblast of guinea
      pigs].
AB  - OBJECTIVE: To investigate the expression of signal transducers and activators of
      transcription 3 (STAT3) in sclera fibroblast of guinea pigs for understanding
      whether STAT3 signaling transduction pathway induced by the insulin-like growth
      factor-1 (IGF-1) was constitutively activated. METHODS: Immunocytochemical
      staining was used to determine the protein levels of STAT3 and P-STAT3 (activated
      STAT3) in scleral fibroblasts. RT-PCR was used to detect the mRNA of STAT3. The
      effects of IGF-1 on scleral fibroblast proliferation were measured by MTT assay.
      RESULTS: Immunocytochemical staining and RT-PCR revealed that STAT3 protein and
      mRNA were over-expressed in the cells which contained constitutively activated
      STAT3 signaling transduction pathway (t=-6.925, -10.179 and 9.363; P<0.001). The
      results of MTT showed that IGF-1 induced fibroblasts proliferation significantly
      at concentrations of 0.5, 1.0, 10.0 microg/L (P<0.05). CONCLUSION: STAT3
      signaling transduction pathway is constitutively activated in the treated scleral
      cells by IGF-1, suggesting that STAT3 signaling transduction pathway may play a
      critical role in the occurrence of myopia and sclera remodeling.

PMID- 18331686
TI  - [Pigment epithelium-derived factor expression in the retina in response to
      hypobaric hypoxia].
AB  - OBJECTIVE: The present study was undertaken to examine the expression of pigment
      epithelium-derived factor (PEDF) in the retina of adult rat following hypobaric
      hypoxic exposures. METHODS: Forty-eight adult Wistar rats were divided into 6
      groups randomly (8 rats in each group), of which 5 groups (40 rats) were
      subjected to hypobaric hypoxia for 2 hours following which expression of PEDF in
      the retina was investigated from 3 hours to 14 days by real time RT-PCR, western
      blotting and immunohistochemistry. RESULTS: PEDF mRNA and protein expression in
      the retina was decreased at 3 hours to 14 days following exposure to hypoxia.
      Compared with normal control group (1.00+/-0.00), PEDF mRNA expression decreased
      to 0.83+/-0.05 at 3 hours, 0.72+/-0.04 at 24 hours, 0.56+/-0.04 at 3 days, 0.54+/
      0.05 at 7 days and 0.49+/-0.05 at 14 days respectively; Compared with normal
      control group (1.90+/-0.02), PEDF protein expression decreased to 1.49+/-0.02 at
      3 hours, 1.19+/-0.05 at 24 hours, 1.15+/-0.05 at 3 days, 1.09+/-0.06 at 7 days
      and 1.07+/-0.03 at 14 days respectively. CONCLUSIONS: The findings of this study
      indicate hypoxia can downregulate PEDF in adult retina.

PMID- 18331690
TI  - [Factors affecting orbital abnormal development and its relevant treatments].
AB  - Orbital development is associated with the growth of the eyeball. During the
      development period, congenital or acquired changes of volume of the eyes and
      radiation treatment in ocular region influence the development of the orbit.
      Abnormal development of the orbit influences craniomaxillofacial growth and
      person's overall aesthetics of the face afterwards. Reconstruction of contracted
      sockets and shrunken orbits poses significant difficulties and obstacles that
      often results in universal frustration and disappointment results. Various
      methods have been used to improve these abnormalities. There are substantial
      different opinions regarding which method offers the best outcome. Traditional
      methods involve using progressively enlarging conformers, static spherical
      orbital implants, demis-fat grafts, and inflatable balloon expanders for orbital
      enlargement. Recently, the self-expander hydrogel tissue expander is available
      that expanders our option. This article reviews the influence of ocular
      abnormalities on the development of the orbit, as well as the advantages and
      disadvantages of various treatments for promoting the development of the orbit.

PMID- 18331692
TI  - [Review of breast pathology: diagnosed by fine needle aspiration and correlation
      between cytological and histological findings].
AB  - The 980 exams concerning breast pathology performed in an 18-month period,
      including 626 fine needle aspiration biopsies, were reviewed. A diagnosis was
      made in 78.2% of fine needle aspiration biopsies, and in the remaining 21.8% they
      were considered insufficient for diagnosis. It was possible to establish a
      correlation with histological findings in 109 cases. There was accordance in
      87.2% of the cases, a discrepancy in 6.4% of the cases neither with false
      positives nor false negatives, and in the remaining cases fine needle aspiration
      biopsy was considered insufficient for diagnosis despite the presence of a lesion
      in histological sections. The advantages and pitfalls of fine needle aspiration
      are discussed, and we consider this technique important in the initial approach
      to patients with breast disorders.

PMID- 18331693
TI  - [Adverse childhood experiences in adults with morbid obesity].
AB  - Research has shown that morbid obesity adults have more adverse childhood
      experiences. The aim of our work was to study the prevalence of this experience
      in a sample with 75 participants with morbid obesity (weight range of 118.57 Kg)
      candidate to bariatric surgery. Sixty-six (88%) participants had at least one
      adverse childhood experience, 51 (68%) refer at least four adverse experiences.
      The results suggest that a large number of participants had adverse childhood
      experiences, and food behaviour should be understood attending to the whole life
      of the individual.

PMID- 18331694
TI  - [Nutritional status recording in hospitalized patient notes].
AB  - The prevalence of disease-related malnutrition (DRM) is described to be of 30-60%
      on admission to hospital, and of 10% in the community. It has been associated
      with worse clinical outcomes, namely higher morbidity and mortality as well as
      higher frequency of health care and its associated costs. The lack of screening
      and monitoring of nutritional status have been said to be risk factors for the
      increased prevalence of DRM during hospital stay. The aims of this study were to
      evaluate the importance given by health care professionals to certain aspects
      related with nutritional status (weight, food intake) of hospital patients and to
      see if there were any differences between the under and non undernourished ones.
      A systematic sample of patients from six hospitals was collected. Pregnancy,
      paediatric age and critical illness were exclusion criteria as well as incapacity
      to fulfil nutritional risk screening protocol and length-of-stay less than 24h.
      Socio-demographic, anthropometric data and clinical notes (e.g. weight,
      food/nutrient intake) from medical records were collected and Nutritional Risk
      Screening 2002 protocol was applied. A total of 1152 patients were included in
      this study. The prevalence of nutritional risk varied between 28.5% and 47.3%
      while undernutrition classified by anthropometrical parameters was considerably
      lower (6.3% to 14.9%). Two thirds of the patients had their food intake monitored
      and registered in medical records but only one third were weighted.
      Undernourished patients had their food intake more frequently monitored but their
      weight was less frequently measured, than the well-nourished ones. DRM prevalence
      amongst hospital patients on admission is significantly high. Clinical notes
      regarding nutritional status is rather infrequent on medical records. This study
      showed that urges the need to empower health care providers of the importance of
      the screening and monitoring of weight and food intake, on admission and during
      hospital stay.

PMID- 18331695
TI  - [Psychometric properties of the Eating Disorders Inventory among Portuguese
      adolescents].
AB  - INTRODUCTION: Although Eating Disorders Inventory (EDI) was developed with
      adults, a large amount of research about eating disorders in adolescents is
      usually conducted with EDI. The clinical and research utility of this instrument
      would be improved by analysing its psychometric properties when used with younger
      people than those in the original standardization samples. The main objective of
      our study is to analyse the psychometric properties of the Eating Disorders
      Inventory (EDI) among 13 year old Portuguese adolescents. METHODS: A sample of
      1184 adolescents (641 girls and 543 boys) born in 1990 and attending public and
      private schools in Porto completed EDI and was evaluated with Stunkard Figure
      Scale at school. Anthropometric measurements were also performed. Internal
      consistency was analysed trough item-total correlations and Cronbach's alpha
      coefficients. Mann-Whitney and Kruskal-Wallis tests were used to evaluate
      construct validity. RESULTS: After the exclusion of 17 of the 64 items that
      showed low consistency, a correlation matrix of seven principal components, that
      explained 49.8% of the total variance, was obtained. In this matrix, 8 subscales
      with alpha ranging from 0.53 to 0.87 were defined. The three core EDI subscales
      (Drive for Thinness, Bulimia and Body Dissatisfaction) presented good
      psychometric properties and, except item 1 (item-total correlation= 0.00), items
      showed good internal consistency (item-total correlations ranging from 0.41 and
      0.73, Cronbach's alpha ranging from 0.77 and 0.87). In accordance with
      theoretical constructs previously defined, girls presented higher mean scores
      than boys on Drive for Thinness subscale (4.0 vs. 1.7, p < 0.001). Also,
      adolescents with a healthy weight presented significantly lower scores than
      overweight adolescents in the same subscale. Boys and girls classified as
      dissatisfied or very dissatisfied with body image according to Stunkard Figure
      Rating Scale presented significantly higher scores on Body Dissatisfaction EDI
      subscale. CONCLUSION: The Portuguese version of EDI, with the proposed changes,
      showed good psychometric characteristics to evaluate symptoms associated with
      eating disorders among 13 year old adolescents. The subscales Drive for Thinness,
      Bulimia and Body Dissatisfaction, besides presenting good psychometric
      properties, remained similar to the same subscales in the original EDI. The
      instrument is able to distinguish groups according to theoretical constructs.

PMID- 18331696
TI  - [Cultural adaptation and validation of the Medical Outcomes Study Social Support
      Survey questionnaire (MOS-SSS)].
AB  - The aim of this study was the assesment of psychometric properties of the
      Portuguese version of the instrument "Medical Outcomes Study - Social Support
      Survey (MOSSSS)". This questionnaire has been translated and adapted in a
      Portuguese sample of 101 patients with chronic illness of a rural health centre
      in Portugal. The average age of patients was 63.4 years, 56.4% female. 29% were
      illiterate and 2% had completed high school. 78% had arterial hypertension and
      the 56.4% had diabetes mellitus type 2. The internal consistency was evaluated
      using Cronbach's alpha. Exploratory and Confirmatory factor analysis were
      performed in order to confirm reliability and validity of the scale and its
      multidimensional characteristics. The 2-week test-retest reliability was
      estimated using weighted kappa for the ordinals variables and intraclass
      coefficient correlation for the quantitative variables. Cronbach's alphas for the
      subscales ranged from 0.873 to 0.967 at test, and 0.862 to 0.972 at retest.
      Exploratory factor analysis revealed the existence of four factors (emotional,
      tangible, positive interaction and affection support) that explain the 72.71% of
      the variance. Confirmatory factor analysis supported the existence of four
      factors that allowed the application of the scale with original items. The
      goodness-of-fit measures corroborate the initial structure, with chi2/ df=2.01,
      GFI=0.998, CFI=0.999, AGFI=0.998, TLI=0.999, NFI=0.998, SRMR=0.332, RMSEA=0.76.
      The 2-weeks test-retest reliability of the Portuguese MOS-SSS as measured by the
      intraclass correlation coefficient was ranged from 0.941 to 0.966 for the four
      dimensions and the overall support index. The weighted kappa was ranged from 0.67
      to 0.87 for all the items. The MOS-SSS Portuguese version demonstrates good
      psychometric properties and seems to be useful to measure multidimensional
      aspects of social support in the Portuguese population.

PMID- 18331697
TI  - [Need of new clinical criteria for the identification of genetic Lynch syndrome].
AB  - BACKGROUND: Surveillance programs in families with Hereditary Non-Polyposis
      Colorectal Cancer (HNPCC), which is an autossomal dominant disease, decrease
      colorectal carcinoma mortality. There are multiple clinical criteria for the
      identification of these families, mainly: the Amsterdam Criteria (ACI), the
      modified Amsterdam Criteria (ACII) and the Bethesda Guidelines (BG). AIMS: To
      correlate, in families with HNPCC, the clinical criteria with the probability of
      detecting a germ-line mutation in MLH1, MSH2 and MSH6 mismatch repair genes.
      METHODS: We included 92 affected patients belonging to different families.
      Clinical criteria leading to HNPCC diagnosis were evaluated. Germ-line mutations
      in MLH1, MSH2 and MSH6 genes were performed by DGGE/MLPA and direct sequencing.
      RESULTS: Germ-line mutations were detected in 54/92 (59%) families, 30 in MLH1,
      23 in MSH2 and 1 in MSH6. Germ-line mutation detection was significantly lower in
      ACI without age criteria (0%), when compared to: ACI (60%), ACII (62%), ACII
      without age criteria (67%) and BG (61%). CONCLUSIONS: The classic, modified AC
      and BG allowed the detection of an identical percentage of families with mutation
      positive HNPCC. The absence of the age criteria in the ACI makes the HNPCC
      diagnosis highly unlikely. Simpler and uniform criteria should be elaborated, to
      allow a homogeneous identification of families with HNPCC.

PMID- 18331698
TI  - [Etiology of urinary tract infections and antimicrobial susceptibility of urinary
      pathogens].
AB  - With the objective of knowing the common etiological agents in urinary infection
      and comparing its antimicrobial susceptibility in nosocomial and community
      acquired urinary infections, we analyse all the urine bacteriological exams from
      the Servico de Patologia Clinica do Centro Hospitalar do Nordeste, EPE - Unidade
      Hospitalar de Braganca, during a two years period (April 2004 to March 2006).
      During this period, 4018 urine bacteriological exams were made. The cultural exam
      was positive in 572 samples (144 from nosocomial infections and 428 from
      community-acquired urinary infections). The Escherichia coli was the more
      isolated strain (68,4 %), followed by Klebsiella spp (7,9%), Pseudomonas
      aeruginosa (6,1%) and Proteus mirabilis (5,2%). Concerning to antimicrobial
      susceptibility, Escherichia coli and Klebsiella spp showed a high resistance to
      the antimicrobials Amoxicillin, Piperacillin, Cephalothin, Ceftazidim and
      Quinolones. For Enterobacteriaceae Imipenem, Amikacin and Netilmicin were the
      antimicrobials with more level of susceptibility. Imipenem and Amikacin were the
      more efficient antimicrobials against Pseudomonas aeruginosa. Concerning to the
      susceptibility for the same etiological agent, in nosocomial and community
      acquired urinary infections, we founded statistical significant differences in
      the antimicrobials Ticarcillin-clavulanic acid and Collistin for Pseudomonas
      aeruginosa and in the group of antimicrobials from Quinolones for the Proteus
      mirabilis. In the other identified agents there were no statistical significant
      differences for antimicrobials. This study it allows making use of data necessary
      for the knowledge of etiologic urinary infection agents in Braganca and provides
      the information about the antimicrobials resistance, which were necessary to
      initiate an adequate empirical treatment and to elaborate treatment guides.

PMID- 18331699
TI  - [Stroke in HIV-infected patients].
AB  - The spectrum of human immunodeficiency virus infection (HIV) is changing. New
      drug treatments have reduced morbidity and mortality of this disease, therefore
      it is necessary to start treating the HIV infection as a chronical disease. The
      association of the stroke with the HIV infection was inicially thought to be a
      result of other opportunistic infeccions and tumors. However, the vascular
      disease associated with HIV infection has been a subject of research and debate.
      New evidence shows that the vascular diseases could be a threat for the pacients
      doing highly active antirretroviral therapy (HAART). In this paper, we review the
      association between the HIV infection and stroke. Furthermore, we have done an
      analysis of the risk for the stroke on pacients with HIV infection considering
      the changes of the infection spectrum by the introduction of HAART.

PMID- 18331700
TI  - [Viral hepatitis in travellers].
AB  - Considering the geographical asymmetric distribution of viral hepatitis A, B and
      E, having a much higher prevalence in the less developed world, travellers from
      developed countries are exposed to a considerable and often underestimated risk
      of hepatitis infection. In fact a significant percentage of viral hepatitis
      occurring in developed countries is travel related. This results from
      globalization and increased mobility from tourism, international work,
      humanitarian and religious missions or other travel related activities. Several
      studies published in Europe and North America shown that more than 50% of
      reported cases of hepatitis A are travel related. On the other hand frequent
      outbreaks of hepatitis A and E in specific geographic areas raise the risk of
      infection in these restricted zones and that should be clearly identified.
      Selected aspects related with the distribution of hepatitis A, B and E are
      reviewed, particularly the situation in Portugal according to the published
      studies, as well as relevant clinical manifestations and differential diagnosis
      of viral hepatitis. Basic prevention rules considering enteric transmitted
      hepatitis (hepatitis A and hepatitis E) and parenteral transmitted (hepatitis B)
      are reviewed as well as hepatitis A and B immunoprophylaxis. Common clinical
      situations and daily practice "pre travel" advice issues are discussed according
      to WHO/CDC recommendations and the Portuguese National Vaccination Program.
      Implications from near future availability of a hepatitis E vaccine, a currently
      in phase 2 trial, are highlighted. Potential indications for travellers to
      endemic countries like India, Nepal and some regions of China, where up to 30% of
      sporadic cases of acute viral hepatitis are caused by hepatitis E virus, are
      considered. Continued epidemiological surveillance for viral hepatitis is
      essential to recognize and control possible outbreaks, but also to identify new
      viral hepatitis agents that may emerge as important global health issues.

PMID- 18331701
TI  - [Development of a multidimensional system for classification and management of
      health information: applying to clinical information].
AB  - INTRODUCTION: The large amount of information in the medical area creates
      management problems, being necessary systematic methods for filing and retrieval.
      With information on the context of clinical records, methods must integrate
      controlled biomedical terminologies and desirable characteristics oriented to the
      structure, content and clinical results. The objective is to test the
      applicability and capacity for retrieval of a multidimensional system developed
      for classification and management of health information. METHODS: Three hundred
      questions were randomly selected, by computerized method, from the questions
      received in six years (Medicine Information Service, Pharmaceutical Department,
      Coimbra University Hospitals). They were characterized and applicability
      evaluated by classified amount and need to alter the system, which is composed of
      various independent dimensions, incorporating concepts sometimes hierarchical.
      Questions retrieval was tested searching information in a dimension or between
      dimensions. RESULTS: All questions were classified: 53% are clinical cases with
      illnesses incidence in the genitourinary system; metabolic, nutritional and
      endocrine disease; cancer; infections and nervous system. In 81%, the object is a
      drug, mostly anti-infectious and anti-neoplastic agents. The therapeutic and
      safety areas had been the most requested, regarding the subjects: use, adverse
      reactions, drug identification and pharmaceutical technology. As to
      applicability, it was necessary to add some concepts and modify same hierarchical
      groups, that didn't modify the basic structure, nor had collided with the
      desirable characteristics. The limitations were related with the incorporated
      external classification systems. The search in the subject dimension of the
      concept drug administration retrieved 19 questions. The search between two
      dimensions: antiinfectious (external) and teratogenicity (subject) retrieved
      three questions. In the two examples, it was possible to retrieve information
      from any one of the levels of the hierarchy, from the most general to the most
      specific and even from external dimensions. CONCLUSIONS: The use of the system in
      this sample showed its applicability in clinical information classification and
      filing, retrieval capacity and flexibility, supporting modifications without
      interfering with desirable characteristics. This tool allows retrieval of patient
      oriented evidence that matters.

PMID- 18331702
TI  - [XYY male with right aortic arch and ligamentum arteriosum: a fortuitus
      association?].
AB  - INTRODUCTION: The XYY male has characteristicaly tall stature, behavior problems
      and speech delay. There may may be an association with nephro-urologic
      malformations but cardiovascular anomalies are usually not present. CASE REPORT:
      It is reported a case of a boy with a 47 XYY karyotype with persistent
      respiratory distress and swallowing difficulties since two months old. On
      diagnosis workup the fiberoptic bronchoscopy showed a significant pulsatil
      tracheal obstruction at its right lateral wall and the magnetic resonance imaging
      of the mediastinum comproved the presence of a vascular ring (right aortic arch
      with left ligamentum arteriosum). The patient was submitted to surgery with
      improvment in the respiratory symptoms. DISCUSSION: The XYY male is a sex
      chromosomal abnormality that usually is not associated with cardiovascular
      malformations. A vascular ring presents with persistent respiratory distress and
      feeding difficulties; the begining and severity of the symptoms varies with the
      type of vascular ring. The main procedure to be requested is the fiberoptic
      bronchoscopy and the best image study is the magnetic resonance imaging of the
      mediastinum.

PMID- 18331703
TI  - [Splenic metastasis in ovary serous adenocarcinoma].
AB  - Splenic metastasis is rare, and is usually associated with disseminated
      malignancy. The primary tumours more frequently related with splenic metastasis
      are lung, breast, gynaecologic, specially ovary tumours, colon, rectum and
      melanoma. Isolated secondary splenic disease is rare, but it is described, often
      associated to ovary cancer. We report a 55 years old women with parenchymal
      splenic metastases of serous ovary cystadenocarcinoma in the 5th follow up year.
      This patient had positive peritoneal washings chytology but not macroscopic
      disease. We discuss the secondary splenic involvement of ovary cancer,
      dissemination route, prognosis and role of splenectomy as treatment modality in
      this unusual recurrence site in ovary cancers.

PMID- 18331704
TI  - A multi-centre retrospective cohort study comparing the efficacy, safety and cost
      effectiveness of hysterectomy and uterine artery embolisation for the treatment
      of symptomatic uterine fibroids. The HOPEFUL study.
AB  - OBJECTIVES: To examine and compare the medium-term results of hysterectomy and
      uterine artery embolisation (UAE) as a treatment for symptomatic uterine fibroids
      with regard to safety, efficacy, special issues in the UAE group, cost
      effectiveness, and women's own perspectives on the treatments. DESIGN: Data were
      collected locally from patients' hospital records and also from patients
      themselves by postal questionnaire. Questionnaire data included free-text
      comments and this qualitative material was analysed using constant comparison. A
      two-stage probabilistic decision model was designed to estimate UK NHS costs and
      health outcomes in terms of quality-adjusted life-years (QALYs). SETTING:
      Eighteen NHS hospital trusts, 17 in England and one in Scotland. PARTICIPANTS:
      Eligible women (972 UAE, 762 hysterectomies) who had received treatment
      specifically for symptomatic fibroids were identified. INTERVENTIONS: The UAE
      patients were treated by experienced interventional radiologists and all received
      their index UAE prior to the end of 2002, ensuring a minimum 2-year follow-up.
      The average length of follow-up was 8.6 years for the hysterectomy cohort and 4.6
      years for the UAE cohort. MAIN OUTCOME MEASURES: Primary outcome measures were
      complication rates to assess the comparative safety of the two interventions.
      Secondary outcome measures related to treatment efficacy including resolution of
      symptoms and patient-reported satisfaction with treatment. Further efficacy
      outcome measures obtained in the UAE group included fibroid/uterine size
      shrinkage and further treatments required for unresolved fibroid symptoms. Data
      were also gathered on pregnancies post-UAE. RESULTS: Data were available for 1108
      women (649 UAE and 459 hysterectomy). Fewer complications were experienced by
      women in the UAE cohort compared to the hysterectomy cohort: hysterectomy n = 120
      (26.1%), UAE n = 114 (17.6%), adjusted odds ratio 0.48 [95% confidence interval
      (CI) 0.26 to 0.89]. When only the severe/major complications were considered,
      this odds ratio was reduced to 0.25 (95% CI 0.13 to 0.48). Expected general side
      effects of UAE occurred in 32.7% of the UAE cohort, of which 8.9% also
      experienced complications. Obesity and medical co-morbidity predisposed women to
      complications, whereas prophylactic antibiotics appeared to protect against both
      complications and the expected side-effects of UAE. More women in the
      hysterectomy cohort reported relief from fibroid symptoms (89% versus 80% UAE, p
      less than 0.0001) and feeling better (81% versus 74% UAE, p less than 0.0001),
      but only 70% (compared with 86% UAE, p = 0.007) would recommend their treatment
      to a friend. In the UAE cohort, 18.3% of the women went on to receive one or more
      further fibroid treatments including hysterectomy (11.2%). After adjusting for
      differential time of follow-up, the UAE women had up to a 23% (95% CI 19 to 27%)
      likelihood of requiring further treatment. The free-text data indicated that many
      women, in both cohorts, felt that their treatment had been a complete success. In
      the UAE cohort there were several areas where expectations were apparently high
      and outcome had not fulfilled their expectations. Disappointment was expressed
      mainly about continuation or return of symptoms or failure to become pregnant.
      Many continued to have remaining questions about their treatment. The economic
      analysis indicated that UAE is less expensive than hysterectomy even after
      further treatments for unresolved or recurrent symptoms are taken into account,
      with little difference in QALYs between the two treatments. Younger women are
      exposed to the risk of recurrent fibroids and subsequent additional procedures
      over a longer period and consequently UAE may no longer be cost-effective.
      CONCLUSIONS: The study results suggest that both UAE and hysterectomy are safe.
      No unexpected problems were detected following UAE after a long follow-up period
      (average 5 years). Complications are less common for UAE than hysterectomy. The
      cost-effectiveness analysis favours embolisation even after taking account of
      complications, expected side-effects associated with the procedure and subsequent
      re-treatments for women with a preference for uterus preservation. It is
      important to improve the management of expectations following UAE, particularly
      regarding fertility. The data suggested that fertility and miscarriage rate are
      consistent with those of age-matched women with fibroids. UAE is an effective
      treatment for some women with fibroids and our trial supports the National
      Institute for Health and Clinical Excellence guidance that it should be made
      available as one of the options for treatment, with a possible reduction in the
      need for hysterectomy as the first-line treatment. Further research is needed
      into which women will be treated most successfully by UAE, the best method of
      achieving effective embolisation, advice for women who desire future fertility,
      the role of prophylactic antibiotics in UAE, and the effects of HRT use after UAE
      on recurrence of fibroid symptoms.

PMID- 18331705
TI  - Methods of prediction and prevention of pre-eclampsia: systematic reviews of
      accuracy and effectiveness literature with economic modelling.
AB  - OBJECTIVES: To investigate the accuracy of predictive tests for pre-eclampsia and
      the effectiveness of preventative interventions for pre-eclampsia. Also to assess
      the cost-effectiveness of strategies (test-intervention combinations) to predict
      and prevent pre-eclampsia. DATA SOURCES: Major electronic databases were searched
      to January 2005 at least. REVIEW METHODS: Systematic reviews were carried out for
      test accuracy and effectiveness. Quality assessment was carried out using
      standard tools. For test accuracy, meta-analyses used a bivariate approach.
      Effectiveness reviews were conducted under the auspices of the Cochrane Pregnancy
      and Childbirth Group and used standard Cochrane review methods. The economic
      evaluation was from an NHS perspective and used a decision tree model. RESULTS:
      For the 27 tests reviewed, the quality of included studies was generally poor.
      Some tests appeared to have high specificity, but at the expense of compromised
      sensitivity. Tests that reached specificities above 90% were body mass index
      greater than 34, alpha-foetoprotein and uterine artery Doppler (bilateral
      notching). The only Doppler test with a sensitivity of over 60% was resistance
      index and combinations of indices. A few tests not commonly found in routine
      practice, such as kallikreinuria and SDS-PAGE proteinuria, seemed to offer the
      promise of high sensitivity, without compromising specificity, but these would
      require further investigation. For the 16 effectiveness reviews, the quality of
      included studies was variable. The largest review was of antiplatelet agents,
      primarily low-dose aspirin, and included 51 trials (36,500 women). This was the
      only review where the intervention was shown to prevent both pre-eclampsia and
      its consequences for the baby. Calcium supplementation also reduced the risk of
      pre-eclampsia, but with some uncertainty about the impact on outcomes for the
      baby. The only other intervention associated with a reduction in RR of pre
      eclampsia was rest at home, with or without a nutritional supplement, for women
      with normal blood pressure. However, this review included just two small trials
      and its results should be interpreted with caution. The cost of most of the tests
      was modest, ranging from 5 pounds for blood tests such as serum uric acid to
      approximately 20 pounds for Doppler tests. Similarly, the cost of most
      interventions was also modest. In contrast, the best estimate of additional
      average cost associated with an average case of pre-eclampsia was high at
      approximately 9000 pounds. The results of the modelling revealed that prior
      testing with the test accuracy sensitivities and specificities identified
      appeared to offer little as a way of improving cost-effectiveness. Based on the
      evidence reviewed, none of the tests appeared sufficiently accurate to be
      clinically useful and the results of the model favoured no-test/treat-all
      strategies. Rest at home without any initial testing appeared to be the most cost
      effective 'test-treatment' combination. Calcium supplementation to all women,
      without any initial testing, appeared to be the second most cost-effective. The
      economic model provided little support that any form of Doppler test has
      sufficiently high sensitivity and specificity to be cost-effective for the early
      identification of pre-eclampsia. It also suggested that the pattern of cost
      effectiveness was no different in high-risk mothers than the low-risk mothers
      considered in the base case. CONCLUSIONS: The tests evaluated are not
      sufficiently accurate, in our opinion, to suggest their routine use in clinical
      practice. Calcium and antiplatelet agents, primarily low-dose aspirin, were the
      interventions shown to prevent pre-eclampsia. The most cost-effective approach to
      reducing pre-eclampsia is likely to be the provision of an effective, affordable
      and safe intervention applied to all mothers without prior testing to assess
      levels of risk. It is probably premature to suggest the implementation of a treat
      all intervention strategy at present, however the feasibility and acceptability
      of this to women could be explored. Rigorous evaluation is needed of tests with
      modest cost whose initial assessments suggest that they may have high levels of
      both sensitivity and specificity. Similarly, there is a need for high-quality,
      adequately powered randomised controlled trials to investigate whether
      interventions such as advice to rest are indeed effective in reducing pre
      eclampsia. In future, an economic model should be developed that considers not
      just pre-eclampsia, but other related outcomes, particularly those relevant to
      the infant such as perinatal death, preterm birth and small for gestational age.
      Such a modelling project should make provision for primary data collection on the
      safety of interventions and their associated costs.

PMID- 18331706
TI  - Early changes in insulin receptor signaling and pain sensation in streptozotocin
      induced diabetic neuropathy in rats.
AB  - The objective of the present study was to evaluate the time course of changes in
      peripheral nerve insulin receptor (IR) signaling and compare observed findings
      with behavioral responses to noxious mechanical and thermal stimuli in
      streptozotocin (STZ)-diabetic rats over 12 weeks of diabetes. Diabetic rats
      developed mechanical hyperalgesia, as indicated by decreased paw withdrawal
      thresholds to mechanical stimuli that were detectable after 2 weeks of diabetes;
      they also developed thermal hypoalgesia, as indicated by increased tail flick
      latencies to thermal stimuli that were detectable at 1 week of diabetes. Western
      blot analysis revealed decreased phosphorylated: total IR protein ratio that was
      detectable as early as 2 weeks of diabetes, whereas phosphorylated:total Akt
      protein ratio was decreased at 2 weeks and increased at 12 weeks of diabetes with
      unchanged PI-3K protein levels. To our knowledge, the present study is the first
      to demonstrate that impaired peripheral nerve IR signaling, as indicated by
      decreased phosphorylated:total IR protein ratio, coincides with early mechanical
      hyperalgesia and thermal hypoalgesia in STZ-diabetic rats. This finding may
      improve understanding of how altered pain sensation develops rapidly in this
      model. PERSPECTIVE: This study examined peripheral nerve IR signaling during the
      early course of altered nociception in STZ-diabetic rats. In diabetic rats,
      impaired peripheral nerve IR signaling is observed shortly after STZ injection,
      as is altered nociception. This finding suggests a possible role of impaired IR
      signaling in diabetic sensory neuropathy.

PMID- 18331707
TI  - Hungry for blood vessels: linking metabolism and angiogenesis.
AB  - A new study by Arany et al. demonstrates that the metabolic master regulator
      peroxisome proliferator-activated receptor (PPARgamma) coactivator-1alpha (PGC
      1alpha) can promote angiogenesis. These findings show that alterations in
      metabolic homeostasis are linked to angiogenesis, which raises exciting
      opportunities for novel proangiogenic and antiangiogenic therapies in various
      diseases.

PMID- 18331708
TI  - Yorkie and Scalloped: partners in growth activation.
AB  - The Hippo (Hpo) signaling pathway limits organ growth in organisms from
      Drosophila to mammals by suppressing the activity of the transcriptional
      coactivator Yorkie (Yki)/YAP. The TEAD/TEF factor Scalloped (Sd) has been
      identified as the first known transcription factor to partner with Yki as a
      downstream target of Hpo signaling.

PMID- 18331709
TI  - Signaling to nuclear transport.
AB  - In a recent issue of Molecular Cell, Yoon et al. provide evidence for the control
      of nucleocytoplasmic transport by protein kinase signaling pathways through
      phosphorylation of RanBP3, an accessory factor in the Ran GTPase system. This
      mechanism may coordinate nucleocytoplasmic transport with other mitogenic effects
      of these pathways.

PMID- 18331710
TI  - Plant cell polarity: sterols enter into action after cytokinesis.
AB  - In yeast and animal cells, the sterol composition of membranes is a key factor
      that controls the polarity of membrane proteins by regulating their intracellular
      trafficking or lateral diffusion. A recent study in Nature Cell Biology
      demonstrates that plant sterols play a major role in the acquisition of cell
      polarity by modulating endocytosis after cell division.

PMID- 18331711
TI  - sSgo1, a guardian of centriole cohesion.
AB  - Sgo1 plays a key role in protecting sister chromatid cohesion during mitosis. In
      this issue of Developmental Cell, Wang et al. describe a shorter splice variant
      of Sgo1 (sSgo1) that functions specifically in centriole cohesion. sSgo1 may be
      the "glue" that holds paired centrioles together in an engaged state before their
      disengagement in late mitosis.

PMID- 18331712
TI  - Wnt/beta-catenin signaling: turning the switch.
AB  - The regulation of many targets of the Wnt/beta-catenin signaling pathway is
      thought to occur through a transcriptional switch that is achieved by beta
      catenin binding to TCF transcription factors. Recent work indicates that beta
      catenin's intrinsic affinity for TCF is not sufficient for the switch to occur.

PMID- 18331713
TI  - Intron delays and transcriptional timing during development.
AB  - The time taken to transcribe most metazoan genes is significant because of the
      substantial length of introns. Developmentally regulated gene networks, where
      timing and dynamic patterns of expression are critical, may be particularly
      sensitive to intron delays. We revisit and comment on a perspective last
      presented by Thummel 16 years ago: transcriptional delays may contribute to
      timing mechanisms during development. We discuss the presence of intron delays in
      genetic networks. We consider how delays can impact particular moments during
      development, which mechanistic attributes of transcription can influence them,
      how they can be modeled, and how they can be studied using recent technological
      advances as well as classical genetics.

PMID- 18331714
TI  - sSgo1, a major splice variant of Sgo1, functions in centriole cohesion where it
      is regulated by Plk1.
AB  - Shugoshin 1 (Sgo1) functions as a protector of centromeric cohesion of sister
      chromatids in higher eukaryotes. Here, we provide evidence for a previously
      unrecognized role for Sgo1 in centriole cohesion. Sgo1 depletion via RNA
      interference induces the formation of multiple centrosome-like structures in
      mitotic cells that result from the separation of paired centrioles. Sgo1+/-
      mitotic murine embryonic fibroblasts display split centrosomes. Localization
      study of two major endogenous splice variants of Sgo1 indicates that the smaller
      variant, sSgo1, is found at the centrosome in interphase and at spindle poles in
      mitosis. sSgo1 interacts with Plk1 and its spindle pole localization is Plk1
      dependent. Centriole splitting induced by Sgo1 depletion or expression of a
      dominant negative mutant is suppressed by ectopic expression of sSgo1 or by Plk1
      knockdown. Our studies strongly suggest that sSgo1 plays an essential role in
      protecting centriole cohesion, which is partly regulated by Plk1.

PMID- 18331715
TI  - Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating
      cells.
AB  - Cdc42GAP promotes inactivation of Cdc42, a small GTPase whose activation at the
      leading edge by guanine nucleotide exchange factors is critical for cell
      migration. How Cdc42GAP is regulated to ensure proper levels of active Cdc42 is
      poorly understood. Here we show that Nudel, a cytoplasmic dynein regulator,
      competes with Cdc42 for binding Cdc42GAP. Consequently, Nudel can inhibit
      Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner. Both Nudel
      and Cdc42GAP exhibit leading-edge localization in migrating cells. The
      localization of Nudel requires its phosphorylation by Erk1/2. Depleting Nudel by
      RNAi or overexpression of a nonphosphorylatable mutant abolishes Cdc42 activation
      and cell migration. Our data thus uncover Nudel as a regulator of Cdc42 during
      cell migration. Nudel facilitates cell migration by sequestering Cdc42GAP at the
      leading edge to stabilize active Cdc42 in response to extracellular stimuli.
      Excess active Cdc42 may in turn control its own activity by recruiting Cdc42GAP
      from Nudel.

PMID- 18331716
TI  - Crag regulates epithelial architecture and polarized deposition of basement
      membrane proteins in Drosophila.
AB  - The polarized architecture of epithelia relies on an interplay between the
      cytoskeleton, the trafficking machinery, and cell-cell and cell-matrix adhesion.
      Specifically, contact with the basement membrane (BM), an extracellular matrix
      underlying the basal side of epithelia, is important for cell polarity. However,
      little is known about how BM proteins themselves achieve a polarized
      distribution. In a genetic screen in the Drosophila follicular epithelium, we
      identified mutations in Crag, which encodes a conserved protein with domains
      implicated in membrane trafficking. Follicle cells mutant for Crag lose
      epithelial integrity and frequently become invasive. The loss of Crag leads to
      the anomalous accumulation of BM components on both sides of epithelial cells
      without directly affecting the distribution of apical or basolateral membrane
      proteins. This defect is not generally observed in mutants affecting epithelial
      integrity. We propose that Crag plays a unique role in organizing epithelial
      architecture by regulating the polarized secretion of BM proteins.

PMID- 18331717
TI  - PpAtg30 tags peroxisomes for turnover by selective autophagy.
AB  - Autophagy, an intrinsically nonselective process, can also target selective cargo
      for degradation. The mechanism of selective peroxisome turnover by autophagy
      related processes (pexophagy), termed micropexophagy and macropexophagy, is
      unknown. We show how a Pichia pastoris protein, PpAtg30, mediates peroxisome
      selection during pexophagy. It is necessary for pexophagy, but not for other
      selective and nonselective autophagy-related processes. It localizes at the
      peroxisome membrane via interaction with peroxins, and during pexophagy it
      colocalizes transiently at the preautophagosomal structure (PAS) and interacts
      with the autophagy machinery. PpAtg30 is required for formation of pexophagy
      intermediates, such as the micropexophagy apparatus (MIPA) and the pexophagosome
      (Ppg). During pexophagy, PpAtg30 undergoes multiple phosphorylations, at least
      one of which is required for pexophagy. PpAtg30 overexpression stimulates
      pexophagy even under peroxisome-induction conditions, impairing peroxisome
      biogenesis. Therefore, PpAtg30 is a key player in the selection of peroxisomes as
      cargo and in their delivery to the autophagy machinery for pexophagy.

PMID- 18331718
TI  - Distinct mechanisms of apoptosis-induced compensatory proliferation in
      proliferating and differentiating tissues in the Drosophila eye.
AB  - In multicellular organisms, apoptotic cells induce compensatory proliferation of
      neighboring cells to maintain tissue homeostasis. In the Drosophila wing imaginal
      disc, dying cells trigger compensatory proliferation through secretion of the
      mitogens Decapentaplegic (Dpp) and Wingless (Wg). This process is under control
      of the initiator caspase Dronc, but not effector caspases. Here we show that a
      second mechanism of apoptosis-induced compensatory proliferation exists. This
      mechanism is dependent on effector caspases which trigger the activation of
      Hedgehog (Hh) signaling for compensatory proliferation. Furthermore, whereas Dpp
      and Wg signaling is preferentially employed in apoptotic proliferating tissues,
      Hh signaling is activated in differentiating eye tissues. Interestingly, effector
      caspases in photoreceptor neurons stimulate Hh signaling which triggers cell
      cycle reentry of cells that had previously exited the cell cycle. In summary,
      dependent on the developmental potential of the affected tissue, different
      caspases trigger distinct forms of compensatory proliferation in an apparent
      nonapoptotic function.

PMID- 18331719
TI  - Genome-wide identification of Smad/Foxh1 targets reveals a role for Foxh1 in
      retinoic acid regulation and forebrain development.
AB  - Foxh1, a Smad DNA-binding partner, mediates TGFbeta-dependent gene expression
      during early development. Few Foxh1 targets are known. Here, we describe a genome
      wide approach that we developed that couples systematic mapping of a functional
      Smad/Foxh1 enhancer (SFE) to Site Search, a program used to search annotated
      genomes for composite response elements. Ranking of SFEs that are positionally
      conserved across species yielded a set of genes enriched in Foxh1 targets.
      Analysis of top candidates, such as Hesx1, Lgr4, Lmo1, Fgf8, and members of the
      Aldh1a subfamily, revealed that Foxh1 initiates a transcriptional regulatory
      network within the developing anterior neuroectoderm. The Aldh1a family is
      required for retinoic acid (RA) synthesis, and, in Foxh1 mutants, expression of
      Aldh1a1, -2, and -3 and activation of a RA-responsive transgenic reporter is
      abolished in anterior structures. Integrated mapping of a developmental
      transcription factor network thus reveals a key role for Foxh1 in patterning and
      initiating RA signaling in the forebrain.

PMID- 18331720
TI  - Ajuba LIM proteins are snail/slug corepressors required for neural crest
      development in Xenopus.
AB  - Snail family transcriptional repressors regulate epithelial mesenchymal
      transitions during physiological and pathological processes. A conserved SNAG
      repression domain present in all vertebrate Snail proteins is necessary for
      repressor complex assembly. Here, we identify the Ajuba family of LIM proteins as
      functional corepressors of the Snail family via an interaction with the SNAG
      domain. Ajuba LIM proteins interact with Snail in the nucleus on endogenous E
      cadherin promoters and contribute to Snail-dependent repression of E-cadherin.
      Using Xenopus neural crest as a model of in vivo Snail- or Slug-induced EMT, we
      demonstrate that Ajuba LIM proteins contribute to neural crest development as
      Snail/Slug corepressors and are required for in vivo Snail/Slug function. Because
      Ajuba LIM proteins are also components of adherens junctions and contribute to
      their assembly or stability, their functional interaction with Snail proteins in
      the nucleus suggests that Ajuba LIM proteins are important regulators of
      epithelia dynamics communicating surface events with nuclear responses.

PMID- 18331721
TI  - Two cell lineages, myf5 and myf5-independent, participate in mouse skeletal
      myogenesis.
AB  - In skeletal muscle development, the myogenic regulatory factors myf5 and myoD
      play redundant roles in the specification and maintenance of myoblasts, whereas
      myf6 has a downstream role in differentiating myocytes and myofibers. It is not
      clear whether the redundancy between myf5 and myoD is within the same cell
      lineage or between distinct lineages. Using lineage tracing and conditional cell
      ablation in mice, we demonstrate the existence of two distinct lineages in
      myogenesis: a myf5 lineage and a myf5-independent lineage. Ablating the myf5
      lineage is compatible with myogenesis sustained by myf5-independent, myoD
      expressing myoblasts, whereas ablation of the myf6 lineage leads to an absence of
      all differentiated myofibers, although early myogenesis appears to be unaffected.
      We also demonstrate here the existence of a significant myf5 lineage within ribs
      that has an important role in rib development, suggested by severe rib defects
      upon ablating the myf5 lineage.

PMID- 18331722
TI  - A mutual inhibition between APC/C and its substrate Mes1 required for meiotic
      progression in fission yeast.
AB  - The anaphase-promoting complex/cyclosome (APC/C) is a cell-cycle-regulated
      essential E3 ubiquitin ligase; however, very little is known about its meiotic
      regulation. Here we show that fission yeast Mes1 is a substrate of the APC/C as
      well as an inhibitor, allowing autoregulation of the APC/C in meiosis. Both
      traits require a functional destruction box (D box) and KEN box. We show that
      Mes1 directly binds the WD40 domain of the Fizzy family of APC/C activators.
      Intriguingly, expression of nonubiquitylatable Mes1 blocks cells in metaphase I
      with high levels of APC/C substrates, suggesting that ubiquitylation of Mes1 is
      required for partial degradation of cyclin B in meiosis I by alleviating Mes1
      inhibitory function. Consistently, a ternary complex, APC/C-Fizzy/Cdc20-Mes1, is
      stabilized by inhibiting Mes1 ubiquitylation. These results demonstrate that the
      fine-tuning of the APC/C activity, by a substrate that is also an inhibitor, is
      required for the precise coordination and transition through meiosis.

PMID- 18331723
TI  - Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors.
AB  - UbcH10 is one of the key regulators of cell cycle progression through the mitotic
      spindle assembly checkpoint pathway. Recently, aberrantly high UbcH10 expression
      has been demonstrated in a variety of malignancies. However, its role in
      astrocytic carcinogenesis is not well defined. This study investigated the splice
      pattern of the UbcH10 gene and its expression status in astrocytomas of different
      grades. Consequently, UbcH10 splice variant 1 (GenBank accession nos. NM_007019)
      was detected in astrocytomas and normal brain tissues by RT-PCR and sequence
      analysis. Expression levels of UbcH10 mRNA were elevated in high- versus low
      grade astrocytomas (64.33+/-60.98 vs 8.36+/-8.15, respectively; p=0.000) or
      normal controls (64.33+/-60.98 vs 1.00+/-1.57, respectively; p=0.000), as
      determined by quantitative real time PCR analysis. Similarly,
      immunohistochemistry study showed increased UbcH10 labelling index in high-grade
      astrocytomas versus low-grade tumors (10.53+/-5.79% vs 4.23+/-2.85%,
      respectively; p=0.000) or normal controls (10.53+/-5.79% vs 0.0+/-0.0%,
      respectively; p=0.000) and, a positive correlation between UbcH10
      immunoreactivity and Ki-67 immunostaining was also noted (Spearman r=0.63,
      p<0.001). These data suggest that overexpression of UbcH10 may serve as one
      important molecular mechanism that underlies the astrocytic carcinogenesis.

PMID- 18331724
TI  - The role of GABAergic transmission in the dentate gyrus on acquisition,
      consolidation and retrieval of an inhibitory avoidance learning and memory task
      in the rat.
AB  - The hippocampal GABAergic interneurons are responsible for controlling the input
      of large principal cell populations, and they thereby determine the oscillatory
      discharge patterns and synaptic plasticity in the hippocampus. Such oscillations
      within neuronal systems serve various complex functions, such as perception,
      cognition, plasticity and memory. The aim of this study is to define the function
      of GABAergic synaptic transmission in the dentate gyrus (DG) of the hippocampus
      in the different stages of inhibitory avoidance (IA) learning and memory in the
      rat. Two cannulae were implanted above the hippocampal DG. Then the rats were
      trained on a step-through IA learning task. Each rat received intra-DG injection
      of picrotoxin (PTX) or saline before training, after training or before the
      retrieval test. The results show that post-training injection of PTX impaired the
      IA memory. On the other hand, pre-training and pre-retrieval injection of PTX had
      no significant effect on the IA activity. Therefore, it seems that GABAergic
      transmission in the DG is involved in the consolidation step (but not in the
      acquisition and retrieval steps) of the IA task by controlling the input to the
      principal cells.

PMID- 18331725
TI  - Differences in the constitutive and SIV infection induced expression of Siglecs
      by hematopoietic cells from non-human primates.
AB  - The expression of the Siglec family of molecules by hematopoietic cells from
      uninfected and SIV infected disease susceptible rhesus macaques (RM) and SIV
      infected disease resistant sooty mangabeys (SM) and for comparison humans was
      carried out. The predominant cell lineage in all three species expressing
      Siglec's was monocytes. The major finding by both a cross sectional and a
      prospective SIV infection study showed that, whereas monocytes from RM show
      marked increase in each Siglec constitutively expressed, monocytes from SM showed
      marked decreases in Siglec-1 expression. While monocytes from all three species
      constitutively expressed Siglec-3, human monocytes in addition expressed Siglec-5
      and -9 and to a lower density 7, monocytes from RM expressed Siglec-7 and those
      from SM expressed Siglec-1. Monocytes from all three species, however, expressed
      mRNA for Siglec-1, -5, -7 and -9. The reasons for the failure to detect these
      molecules at the protein level and the mechanisms for such distinct effects of
      SIV infection on Siglec expression are discussed.

PMID- 18331726
TI  - When can we say 'if'?
AB  - In this study, we focus on the conditions which permit people to assert a
      conditional statement of the form 'if p then q' with conversational relevance. In
      a broadly decision-theoretic approach, also drawing on hypothetical thinking
      theory [Evans, J. St. B. T. (2007). Hypothetical thinking: Dual processes in
      reasoning and judgement. Hove, UK: Psychology Press.], we predicted that
      conditional tips and promises would appear more useful and persuasive and be more
      likely to encourage an action p when (a) the conditional link from p to q was
      stronger, (b) the cost of the action p was lower and (c) the benefit of the
      consequence q was higher. Similarly, we predicted that conditional warnings and
      threats would be seen as more useful and persuasive and more likely to discourage
      an action p when (a) the conditional link from p to q was stronger, (b) the
      benefit of the action p was lower and (c) the cost of the consequence q was
      higher. All predictions were strongly confirmed, suggesting that such
      conditionals may best be asserted when they are of high relevance to the goals of
      the listener.

PMID- 18331727
TI  - Blockade of T-type voltage-dependent Ca2+ channels by benidipine, a
      dihydropyridine calcium channel blocker, inhibits aldosterone production in human
      adrenocortical cell line NCI-H295R.
AB  - Benidipine, a long-lasting dihydropyridine calcium channel blocker, is used for
      treatment of hypertension and angina. Benidipine exerts pleiotropic
      pharmacological features, such as renoprotective and cardioprotective effects. In
      pathophysiological conditions, the antidiuretic hormone aldosterone causes
      development of renal and cardiovascular diseases. In adrenal glomerulosa cells,
      aldosterone is produced in response to extracellular potassium, which is mainly
      mediated by T-type voltage-dependent Ca2+ channels. More recently, it has been
      demonstrated that benidipine inhibits T-type Ca2+ channels in addition to L-type
      Ca2+ channels. Therefore, effect of calcium channel blockers, including
      benidipine, on aldosterone production and T-type Ca2+ channels using human
      adrenocortical cell line NCI-H295R was investigated. Benidipine efficiently
      inhibited KCl-induced aldosterone production at low concentration (3 and 10 nM),
      with inhibitory activity more potent than other calcium channel blockers. Patch
      clamp analysis indicated that benidipine concentration-dependently inhibited T
      type Ca2+ currents at 10, 100 and 1000 nM. As for examined calcium channel
      blockers, inhibitory activity for T-type Ca2+ currents was well correlated with
      aldosterone production. L-type specific calcium channel blockers calciseptine and
      nifedipine showed no effect in both assays. These results indicate that
      inhibition of T-type Ca2+ channels is responsible for inhibition of aldosterone
      production in NCI-H295R cells. Benidipine efficiently inhibited KCl-induced
      upregulation of 11-beta-hydroxylase mRNA and aldosterone synthase mRNA as well as
      KCl-induced Ca2+ influx, indicating it as the most likely inhibition mechanism.
      Benidipine partially inhibited angiotensin II-induced aldosterone production,
      plus showed additive effects when used in combination with the angiotensin II
      type I receptor blocker valsartan. Benidipine also partially inhibited
      angiotensin II-induced upregulation of the above mRNAs and Ca2+ influx inhibitory
      activities of benidipine for aldosterone production. T-type Ca2+ channels may
      contribute to additional benefits of this drug for treating renal and
      cardiovascular diseases, beyond its primary anti-hypertensive effects from
      blocking L-type Ca2+ channels.

PMID- 18331728
TI  - Clathrin dependent endocytosis of E-cadherin is regulated by the Arf6GAP isoform
      SMAP1.
AB  - E-cadherin is a central component of the adherens junction in epithelial cells
      and continuously undergoes endocytosis via clathrin-coated vesicles and/or
      caveolae depending on the cell type. In this study, we examined the role of
      SMAP1, a clathrin-interacting GTPase-activating protein (GAP) for the ADP
      ribosylation factor 6 (Arf6) GTPase, in E-cadherin endocytosis. Mardin-Darby
      canine kidney (MDCK) epithelial cells were used as a model, and SMAP1 localized
      in the cytoplasm and along the adherens junction where E-cadherin was present.
      Next, activity of SMAP1 was compared with that of other Arf6GAPs (and/or an
      effector of Arf6-GTP), namely GIT1 and AMAP2/DDEF2. Overexpression of SMAP1 but
      not GIT1 nor AMAP2/DDEF2 strongly inhibited basal, as well as phorbolester
      induced, internalization of E-cadherin. Notably, AMAP2/DDEF2 rather enhanced the
      caveolae-mediated incorporation of a membrane protein other than E-cadherin.
      Thus, in MDCK cells, E-cadherin appeared to be endocytosed solely through SMAP1
      regulated clathrin-coated vesicles. Furthermore, MDCK cells overexpressing SMAP1
      showed a reduced degree of cell migration compared to untransfected cells, as
      assessed by wound healing and Transwell assays, and this reduction in migration
      appeared to be due to the accumulation of E-cadherin at the adherens junction in
      cells overexpressing SMAP1. Collectively, SMAP1 likely represents a key Arf6GAP
      in clathrin dependent endocytosis of E-cadherin in MDCK cells. This activity of
      SMAP1 in E-cadherin turnover may be involved in epithelial organization and/or
      epithelial-mesenchymal transition.

PMID- 18331729
TI  - Role of acetylcholine receptors in proliferation and differentiation of P19
      embryonal carcinoma cells.
AB  - Coordinated proliferation and differentiation of progenitor cells is the base for
      production of appropriate numbers of neurons and glia during neuronal development
      in order to establish normal brain functions. We have used murine embryonal
      carcinoma P19 cells as an in vitro model for early differentiation to study
      participation of nicotinic (nAChR) and muscarinic acetylcholine (mAChR) receptors
      in the proliferation of neural progenitor cells and their differentiation to
      neurons. We have previously shown that functional nicotinic acetylcholine
      receptors (nAChRs) already expressed in embryonic cells mediate elevations in
      cytosolic free calcium concentration ([Ca2+]i) via calcium influx through nAChR
      channels whereas intracellular stores contribute to nAChR- and mAChR-mediated
      calcium fluxes in differentiated cells [Resende et al., Cell Calcium 43 (2008)
      107-121]. In the present study, we have demonstrated that nicotine provoked
      inhibition of proliferation in embryonic cells as determined by BrdU labeling.
      However, in neural progenitor cells nicotine stimulated proliferation which was
      reversed in the presence of inhibitors of calcium mobilization from intracellular
      stores, indicating that liberation of intracellular calcium contributed to this
      proliferation induction. Muscarine induced proliferation stimulation in
      progenitor cells by activation of Galphaq/11-coupled M1, M3 and M5 receptors and
      intracellular calcium stores, whereas Galphai/o-protein coupled M2 receptor
      activity mediated neuronal differentiation.

PMID- 18331731
TI  - Novel computational models for predicting dopamine interactions.
AB  - Dopamine is a crucial neurotransmitter responsible for functioning and
      maintenance of the nervous system. Dopamine has also been implicated in a number
      of diseases including schizophrenia, Parkinson's disease and drug addiction.
      Dopamine agonists are used in early Parkinson's disease treatment. Dopamine
      antagonists suppress schizophrenia. Therefore, molecules modulating dopamine
      receptors activity are vastly important for understanding the nervous system
      functioning and for the treatment of neurological diseases. In this study we
      describe novel computational models that efficiently predict binding affinity of
      the existing small molecule dopamine analogs to dopamine receptor. The model
      provides the set of molecular descriptors that can be used for the development of
      new small molecule dopamine agonists.

PMID- 18331732
TI  - Genetic transformation of a Corynebacterial symbiont from the Chagas disease
      vector Triatoma infestans.
AB  - Insect-borne diseases have experienced a troubling resurgence in recent years.
      Emergence of resistance to pesticides greatly hampers control efforts.
      Paratransgenesis, or the genetic transformation of bacterial symbionts of disease
      vectors, is an alternative to traditional approaches. Previously, we developed
      paratransgenic lines of Rhodnius prolixus, a vector of Chagas disease in Central
      America. Here, we report identification of a Corynebacterial species as a
      symbiont of Triatoma infestans, a leading vector of Chagas disease in South
      America. We have modified this bacterium to produce an immunologically active
      single chain antibody fragment, termed rDB3. This study establishes the basis for
      generating paratransgenic T. infestans as a strategy for control of Chagas
      disease.

PMID- 18331733
TI  - Schistosoma mansoni: melatonin enhances efficacy of cercarial and soluble worm
      antigens in the induction of protective immunity against infection in the
      hamster.
AB  - Based on the beneficial influence of melatonin administration on the course of
      schistosomiasis and on its possible action on the immune system, we aimed in this
      study to establish an immunization program using Schistosoma mansoni adult worm
      antigen (SWAP) and cercarial antigen (CAP) alone or concurrently with melatonin
      treatment, for 30 successive days, in an attempt to enhance their efficacy
      against the infection in hamsters. Results showed that the worm reduction
      percentages were 53.8%, 67.01%, 56.4% and 99.3% for CAP, CAP+melatonin, SWAP,
      SWAP+melatonin, respectively, indicating that melatonin enhanced efficacy of SWAP
      but only produced a slight increase in efficacy of CAP. Highly significant
      reductions in egg load in the liver and alteration in the oogram pattern with a
      high percentage of immature eggs and few dead eggs were recorded in the groups
      that received melatonin treatment suggesting a possible role for melatonin in the
      regulation of egg production and development. On the other hand, melatonin
      clearly improved the oxidative status in the immunized groups. No antibody (Ab)
      response was recorded in the groups immunized with SWAP+melatonin while low Ab
      level was seen in the other melatonin-treated group. In addition to the
      antioxidant properties of melatonin, our results suggested that the early and
      continuous melatonin administration may result in immunomodulatory actions which
      in turn enhanced the efficacy of SWAP and CAP in different ways. This indicates
      the importance of further investigation of the mechanisms of melatonin action and
      the possible application in a vaccination program.

PMID- 18331735
TI  - Ethical and legal challenges.

PMID- 18331736
TI  - Excessive ovarian response is associated with increased expression of interleukin
      2 in the periimplantation endometrium.
AB  - OBJECTIVE: To evaluate and compare in vivo expression of T helper type 1 (Th1)
      cytokines in the peri-implantation endometrium of infertile patients between
      natural and stimulated cycles. DESIGN: An observational study. SETTING: A
      tertiary assisted reproduction center. PATIENT(S): Infertile patients.
      INTERVENTION(S): Uterine flushings and endometrial biopsies were collected 7 days
      after LH surge in natural cycles or after hCG injection in stimulated cycles.
      MAIN OUTCOME MEASURE(S): T helper type 1 cytokines were determined by
      immunolocalization and by ELISA. RESULT(S): Natural cycles were classified as
      group A (n = 17), whereas stimulated cycles with peak serum E(2) of <or=20,000
      pmol/L (moderate responders) and with peak serum E(2) of >20,000 pmol/L
      (excessive responders) were classified as group B (n = 32) and group C (n = 32),
      respectively. Higher serum E(2) concentration was associated with increased
      expressions of interleukin (IL)-2 in the endometrium and uterine flushing. Group
      C demonstrated a statistically significantly higher IL-2 expression in
      endometrial biopsies by glandular and stromal immunostaining and by ELISA,
      compared with group A and group B. There was no difference in IL-2 concentration
      between group A and group B. Interferon-gamma protein concentration was
      comparable for the three groups. CONCLUSION(S): Increased expression of IL-2 in
      the peri-implantation endometrium may account for the lower implantation rate in
      excessive responders.

PMID- 18331738
TI  - Tissue ingrowth in a fully covered self-expandable metallic stent (with videos).

PMID- 18331737
TI  - Comparison of hormonal and metabolic markers after a high-fat, Western meal
      versus a low-fat, high-fiber meal in women with polycystic ovary syndrome.
AB  - OBJECTIVE: To determine the effect of meal composition on postprandial T levels
      in women with polycystic ovary syndrome (PCOS). DESIGN: Randomized, crossover
      design. SETTING: Academic research center. PATIENT(S): Fifteen women with PCOS.
      INTERVENTION(S): We evaluated changes in T, sex hormone binding globulin (SHBG),
      DHEAS, cortisol, glucose, and insulin for 6 hours after a high-fat, Western meal
      (HIFAT) (62% fat, 24% carbohydrate, 1 g fiber) and an isocaloric low-fat, high
      fiber meal (HIFIB) (6% fat, 81% carbohydrate, 27 g fiber). MAIN OUTCOME
      MEASURE(S): Change in T levels. RESULT(S): Testosterone decreased 27% within 2
      hours after both meals. However, T remained below premeal values for 4 hours
      after the HIFIB meal and 6 hours after the HIFAT meal. Insulin was twofold higher
      for 2 hours after the HIFIB meal compared with the HIFAT meal. Glucose was higher
      for 1 hour after the HIFIB meal compared with the HIFAT meal. DHEAS decreased 8%
      10% within 2-3 hours after both meals, then increased during the remainder of the
      study period. Cortisol decreased during the 6-hour period after both meals.
      CONCLUSIONS: Diet plays a role in the regulation of T levels in women with PCOS.
      Further studies are needed to determine the role of diet composition in the
      treatment of PCOS.

PMID- 18331739
TI  - Production and utilization of interleukin-15 in malignant catarrhal fever.
AB  - Malignant catarrhal fever (MCF) is an often fatal lymphoproliferative disease of
      ungulates caused by either alcelaphine herpesvirus-1 (AlHV-1) or ovine
      herpesvirus-2 (OvHV-2). The pathogenesis of MCF is poorly understood, but appears
      to involve an auto-destructive pathology whereby cytotoxic lymphocytes destroy
      areas of a variety of tissues. The cytokine interleukin-15 (IL-15) is involved in
      the development and maintenance of cytotoxic lymphocytes and may therefore have a
      role in the pathogenesis of MCF. Virus-infected large granular lymphocytes (LGLs)
      were obtained from the tissues of rabbits infected with AlHV-1 or OvHV-2. These
      cells exhibited a similar proliferative response to IL-15 and to IL-2 in culture,
      but their content of the activated cytotoxic enzyme (BLT-esterase) was maintained
      at higher levels in the presence of IL-15 compared with IL-2. The LGLs did not
      express IL-15 mRNA or produce IL-15 protein. By contrast, there was abundant
      expression of IL-15 mRNA and protein in affected tissues. IL-15 production was
      associated with necrotic lesions of the mesenteric lymph node and appendix of
      OvHV-2-infected rabbits, but was not found in the same tissues of rabbits
      infected with AlHV-1 in which there were no necrotic lesions. The cellular source
      of the IL-15 was predominantly lymphoid cells that did not express B cell or
      monocyte-macrophage markers. Only a few IL-15+ cells (<10%) co-localized with pan
      T cells or CD8+ T cells. The abundance of IL-15 in tissue with lesions of MCF
      suggests that this cytokine may have a role in the pathogenesis of MCF.

PMID- 18331740
TI  - Serotonin transporter binding as a possible predictor of one-year remission in
      major depressive disorder.
AB  - OBJECTIVE: Lower serotonin transporter (5-HTT) binding (BP(P)=f(P)B(avail)/K(D))
      is reported during a major depressive episode (MDE) compared to healthy controls.
      Higher 5-HTT binding in the diencephalon has previously been associated with
      acute response to antidepressant treatment. We assessed baseline 5-HTT binding as
      a predictor of one-year remission from a MDE, examining binding in brain regions
      implicated in the pathophysiology of major depressive disorder (MDD). METHODS: 5
      HTT binding was quantified using positron emission tomography (PET) with
      [(11)C]McN5652 in 19 currently depressed subjects with MDD and 41 healthy
      controls. Depressed subjects received open, naturalistic antidepressant
      treatment. Remission status was determined one year after PET scan and treatment
      initiation. RESULTS: Significant differences in 5-HTT binding among the three
      groups (healthy controls, remitters, and non-remitters) were observed in a linear
      mixed-effects model. Post hoc, non-remitters had lower 5-HTT binding than
      controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ
      significantly from controls or non-remitters in 5-HTT binding. Remitters did not
      differ from non-remitters in clinical characteristics apart from greater family
      history of depression among non-remitters. A logistic regression model fit to
      determine the capacity of baseline 5-HTT binding to predict remission status at
      one year yielded a coefficient that was suggestive but not significant (p=0.057).
      LIMITATIONS: The small sample size and heterogeneous treatments received reduced
      statistical power to detect differences in binding based on clinical outcome.
      CONCLUSIONS: Lower pretreatment 5-HTT binding may be predictive of non-remission
      from major depression following one year of naturalistic antidepressant
      treatment. Future studies using standardized treatment are warranted.

PMID- 18331741
TI  - Mental disorders and subsequent educational attainment in a US national sample.
AB  - As part of a larger investigation of the adverse effects of mental disorders on
      role functioning, we examined the associations of early-onset mental disorders
      with subsequent educational attainment in a large nationally representative
      survey of the US adult population. Diagnoses and age of onset for each of 17 DSM
      IV disorders were assessed through retrospective self-report with the fully
      structured WHO Composite International Diagnostic Instrument (CIDI). Survival
      analysis was used to examine the associations between early-onset DSM-IV/CIDI
      disorders and subsequent termination of schooling with controls for socio
      demographic characteristics and childhood adversities (i.e. childhood traumatic
      events, childhood neglect, parental mental illness, family disruption, and low
      parental educational attainment). Mental disorders were found to be significantly
      associated with termination of schooling prior to completion of each of four
      educational milestones (primary school graduation, high school graduation,
      college entry, college graduation), with odds ratios in the range of 1.3-7.0. The
      proportion of school terminations attributable to mental disorders was largest
      for high school graduation (10.2%) but also meaningful for primary school
      graduation (3.8%), college entry (4.4%) and college graduation (2.6%). These
      results add to a growing body of evidence documenting a wide variety of adverse
      life course effects of mental disorders.

PMID- 18331742
TI  - Decreased islet sensitivity to insulin in hamsters with dietary-induced insulin
      resistance.
AB  - In the present study, we evaluated the autocrine modulatory effect of insulin on
      glucose metabolism and glucose-induced insulin secretion in islets isolated from
      hamsters with insulin resistance (IR) induced by administration of a sucrose-rich
      diet (SRD) during 5 weeks. We used an approach of two metabolic pathways (glucose
      oxidation and utilization) based on the measurement of 14CO2 and 3H2O production
      from D-[U-14C]-glucose and D-[5-(3)H]-glucose, respectively, in isolated islets
      incubated with 3.3 and 16.7 mM glucose alone, or with 5 or 15 mU/ml insulin, anti
      insulin guinea-pig serum (1:500), 25 microM nifedipine, or 150 nM wortmannin.
      Insulin release was measured by radioimmunoassay in islets incubated with 3.3 or
      16.7 mM glucose, with or without 75, 150, and 300 nM wortmannin. Results showed
      that the stimulatory effect of insulin upon 14CO2 and 3H2O production in control
      islets was not observed in SRD islets. Addition of anti-insulin serum, nifedipine
      or wortmannin to the medium with 16.7 mM glucose decreased 14CO2 and 3H2O
      production in control but not in SRD islets. Whereas wortmannin did not decrease
      insulin release induced by 16.7 mM glucose in SRD hamsters, it did in controls.
      We can conclude that the autocrine stimulatory effect of insulin upon glucose
      metabolism observed in normal islets is attenuated or even absent in islets from
      IR animals. Such decreased islet sensitivity to insulin did not prevent the
      compensatory secretion of insulin from maintaining glucose homeostasis,
      suggesting that, at least in this model, the islets can put forward alternative
      mechanisms to overcome such defect.

PMID- 18331743
TI  - Effect of linear alkylbenzene sulfonate (LAS) and atrazine on marine microalgae.
AB  - Five marine microalgae (Tetraselmis chuii, Rhodomonas salina, Chaetoceros sp.,
      Isochrysis galbana (T-iso) and Nannochloropsis gaditana), in the same biovolume
      quantity, were exposed to 72h growth-inhibition tests with atrazine and LAS. In
      all cases, the inhibition effect of atrazine was higher than that of LAS up to
      two orders of magnitude higher in the case of T. chuii. In a second part of the
      study, initial cellular densities for each microalga strain and fixed organic
      compound concentration were varied, and results show density has a clear
      influence in growth inhibition tests. Finally, the sum of all data obtained in
      the study was expressed in terms of "toxic cellular quota" (mass of chemical
      substance per cell). The result was a sigmoid curve with a good fit, including
      the two main factors in toxicity tests, initial cellular density and contaminant
      concentration. This toxic cellular quota exhibits a general tendency to increase
      with cell volume/size.

PMID- 18331744
TI  - Interelement relationships and age-related variation of trace element
      concentrations in liver of striped dolphins (Stenella coeruleoalba) from Japanese
      coastal waters.
AB  - Concentrations of 19 trace elements (V, Cr, Mn, Fe, Co, Cu, Zn, Se, Rb, Sr, Mo,
      Ag, Cd, Sb, Cs, Ba, Tl, Hg, and Pb) were determined in the liver of the striped
      dolphins (Stenella coeruleoalba) collected around Japan during 1977-1982 to
      examine the sex difference, age dependence, and interrelationships among trace
      elements. Tissue distribution of trace elements was also investigated in one
      adult and one fetus specimens. Generally, concentrations of Se, Sr, Ag, Cd, Cs,
      Ba, Hg, and Pb were higher in the tissues of adult than those of fetus, whereas
      the opposite trend was observed for Cr and Tl. There were no significant sex
      differences in the trace element levels in the liver. Significant positive
      correlations between age (0-26.5 years) and hepatic concentrations were found for
      Ag, Se, Hg, V, Fe, Pb, and Sr, suggesting their age-dependent accumulation in the
      liver. In contrast, hepatic concentrations of Mn and Zn decreased with age.
      Significant positive relationships were observed between Se, and Hg, Ag, V, Fe,
      and Sr in the liver.

PMID- 18331745
TI  - The Sea Empress oil spill (Wales, UK): effects on Common Scoter Melanitta nigra
      in Carmarthen Bay and status ten years later.
AB  - Carmarthen Bay, UK, regularly supports internationally important numbers
      (>16,000) of non-breeding Common Scoters Melanitta nigra. The spill of 72,000
      tonnes of crude oil from the Sea Empress in 1996 affected birds both through
      direct mortality and likely pollution of key food resources. Numbers were greatly
      reduced following the spill, whilst changes in the distribution of birds within
      Carmarthen Bay suggested that potentially sub-optimal foraging zones were used.
      However, ten years after the incident, numbers of Common Scoter were no different
      to those recorded immediately before the spill. Compared to some other spills,
      rapid revival is evident. Numbers increased to pre-spill levels within three
      winters and distributional changes suggested a concurrent return to previously
      contaminated feeding areas, implying that the ecosystem had regenerated
      sufficiently to support its top predator. The importance of prolonged,
      standardised monitoring of bird numbers and distribution as indicators of
      ecological recovery from environmental damage is emphasised.

PMID- 18331746
TI  - Sensitivity of bacterioplankton nitrogen metabolism to eutrophication in sub
      tropical coastal waters of Key West, Florida.
AB  - Expression of intracellular ammonium assimilation enzymes were used to assess the
      response of nitrogen (N) metabolism in bacterioplankton to N-loading of sub
      tropical coastal waters of Key West, Florida. Specific activities of glutamine
      synthetase (GS) and total glutamate dehydrogenase (GDHT) were measured on the
      bacterial size fraction (<0.8 microm) to assess N-deplete versus N-replete
      metabolic states, respectively. Enzyme results were compared to concentrations of
      dissolved organic matter and nutrients and to the biomass and production of
      phytoplankton and bacteria. Concentrations of dissolved inorganic N (DIN),
      dissolved organic N (DON), and dissolved organic carbon (DOC) positively
      correlated with specific activities of GDHT and negatively correlated with that
      of GS. Total dissolved N (TDN) concentration explained 81% of variance in
      bacterioplankton GDHT:GS activity ratio. The GDHT:GS ratio, TDN, DOC, and
      bacterial parameters decreased in magnitude along a tidally dynamic trophic
      gradient from north of Key West to south at the reef tract, which is consistent
      with the combined effects of localized coastal eutrophication and tidal exchange
      of seawater from the Southwest Florida Shelf and Florida Strait. The N-replete
      bacterioplankton north of Key West can regenerate ammonium which sustains primary
      production transported south to the reef. The range in GDHT:GS ratios was 5-30
      times greater than that for commonly used indicators of planktonic
      eutrophication, which emphasizes the sensitivity of bacterioplankton N-metabolism
      to changes in N-bioavailability caused by nutrient pollution in sub-tropical
      coastal waters and utility of GDHT:GS ratio as an bioindicator of N-replete
      conditions.

PMID- 18331747
TI  - Lethal and estrogenic effects of 4-nonylphenol in the cockle Cerastoderma
      glaucum.
AB  - The lethal and sublethal effects of the xenoestrogen 4-nonylphenol (NP) were
      evaluated in the cockle Cerastoderma glaucum. In a 96-h lethality test, bivalves
      were exposed to 0, 0+ acetone, 0.19, 0.38, 0.75, 1.5 and 3.0 mg NP/l. The 96-h
      LC(50) value was 0.3mg NP/l. No mortality was observed at 0.1 mg NP/l. The
      potential estrogenicity of NP was studied in both sexually undifferentiated
      (resting phase) and differentiated (pre-spawning phase) cockles, exposed for 7
      and 14 days to 0, 0+ acetone, 0.0125, 0.025, 0.05, and 0.1 mg NP/l. Vitellogenin
      (Vg)-like protein levels were determined in both haemolymph and digestive gland
      by the alkali-labile phosphate (ALP) assay. In the resting phase, exposure for 7
      days to 0.1 mg NP/l resulted in significant increases in ALP in both haemolymph
      and digestive gland, compared with controls. A significant increase was also
      observed in digestive gland of animals exposed to 0.0125 mg NP/l-exposed animals.
      After 14 days of exposure, haemolymph ALP levels were significantly increased in
      exposed animals at all NP concentrations tested, whereas no difference was
      recorded in digestive gland. In the pre-spawning phase, exposure for 7 days to NP
      significantly increased ALP levels in haemolymph from males exposed at all NP
      concentrations tested, whereas no significant variations were found in haemolymph
      from females. NP (0.05 and 0.1 mg/l) was also shown to increase ALP
      concentrations significantly in digestive gland of males, but not in those of
      females. Likewise, after 14 days' exposure, ALP levels significantly increased in
      haemolymph from males only at 0.1 mg NP/l. Conversely, NP caused significant
      increases in ALP levels in digestive gland from both males (at all NP
      concentrations tested) and females (at 0.025 and 0.1 mg NP/l). These results
      demonstrate that NP induces Vg synthesis in C. glaucum. Interestingly, males were
      more responsive to NP than females.

PMID- 18331748
TI  - Response of human renal tubular cells to cyclosporine and sirolimus: a
      toxicogenomic study.
AB  - The molecular mechanisms involved in the potentially nephrotoxic response of
      tubular cells to immunosuppressive drugs remain poorly understood.
      Transcriptional profiles of human proximal tubular cells exposed to cyclosporine
      A (CsA), sirolimus (SRL) or their combination, were established using
      oligonucleotide microarrays. Hierarchical clustering of genes implicated in
      fibrotic processes showed a clear distinction between expression profiles with
      CsA and CsA+SRL treatments on the one hand and SRL treatment on the other.
      Functional analysis found that CsA and CsA+SRL treatments preferentially alter
      biological processes located at the cell membrane, such as ion transport or
      signal transduction, whereas SRL modifies biological processes within the nucleus
      and related to transcriptional activity. Genome wide expression analysis
      suggested that CsA may induce an endoplasmic reticulum (ER) stress in tubular
      cells in vitro. Moreover we found that CsA exposure in vivo is associated with
      the upregulation of the ER stress marker BIP in kidney transplant biopsies. In
      conclusion, this toxicogenomic study highlights the molecular interaction
      networks that may contribute to the tubular response to CsA and SRL. These
      results may also offer a new working hypothesis for future research in the field
      of CsA nephrotoxicity. Further studies are needed to evaluate if ER stress
      detection in tubular cells in human biopsies can predict CsA nephrotoxicity.

PMID- 18331749
TI  - Sequential or simultaneous visual processing deficit in developmental dyslexia?
AB  - The ability of dyslexic children with or without phonological problems to process
      simultaneous and sequential visual information was assessed using two tasks
      requiring the oral report of simultaneously or sequentially displayed letter
      strings. The two groups were found to exhibit a simultaneous visual processing
      deficit but preserved serial processing skills. However, the impairment in
      simultaneous processing was larger in the dyslexic group with no phonological
      disorder. Although sequential and simultaneous processing skills both related to
      reading performance, simultaneous processing alone significantly contributed to
      reading speed and accuracy. These findings suggest that a simultaneous processing
      disorder might contribute to developmental dyslexia.

PMID- 18331750
TI  - The influence of chromatic context on binocular color rivalry: perception and
      neural representation.
AB  - The predominance of rivalrous targets is affected by surrounding context when
      stimuli rival in orientation, motion or color. This study investigated the
      influence of chromatic context on binocular color rivalry. The predominance of
      rivalrous chromatic targets was measured in various surrounding contexts. The
      first experiment showed that a chromatic surround's influence was stronger when
      the surround was uniform or a grating with luminance contrast (chromatic/black
      grating) compared to an equiluminant grating (chromatic/white). The second
      experiment revealed virtually no effect of the orientation of the surrounding
      chromatic context, using chromatically rivalrous vertical gratings. These results
      are consistent with a chromatic representation of the context by a non-oriented,
      chromatically selective and spatially antagonistic receptive field. Neither a
      double-opponent receptive field nor a receptive field without spatial antagonism
      accounts for the influence of context on binocular color rivalry.

PMID- 18331751
TI  - Contributions of fermentative acidogenic bacteria and sulfate-reducing bacteria
      to lactate degradation and sulfate reduction.
AB  - The roles of fermentative acidogenic bacteria and sulfate-reducing bacteria (SRB)
      in lactate degradation and sulfate reduction in a sulfidogenic bioreactor were
      investigated by traditional chemical monitoring and culture-independent methods.
      A continuously stirred tank reactor fed with synthetic wastewater containing
      lactate and SO(2-)(4) at 35 degrees C, 10h of hydraulic retention time was used.
      The results showed that sulfate removal efficiency reached 99%, and sulfide and
      acetate were the main end products after 20 d of operation. 16S rRNA gene based
      clone libraries and single-strand conformation polymorphism profiles demonstrated
      that the proportion of SRB increased from 16% to 95%, and that Desulfobulbus
      spp., Desulfovibrio spp., Pseudomonas spp. and Clostridium spp. formed a stable,
      dominant community structure. The decreasing COD/SO(2-)(4) ratio had little
      effect on the community pattern except that Pseudomonas spp. and Desulfobulbus
      spp. increased slightly. The addition of molybdate to the influent significantly
      changed the microbial community, sulfate removal efficiency and the pattern of
      end products. Clostridium spp., Bacteroides spp. and Ruminococcus spp. became the
      dominant community members. The main end products switched from acetate to
      ethanol and then to propionate with the oxidation-reduction potentials increasing
      from -420 to -290 mV. A lactate degradation pathway was deduced: lactate served
      as the electronic donor for Desulfovibrio spp., or was fermented by Clostridium
      spp. and Bacteroides spp. to produce propionate or ethanol, which were
      subsequently utilized by Desulfobulbus spp. and Desulfovibrio spp. The
      acidotrophic SRB oxidized part of the acetate finally.

PMID- 18331752
TI  - In situ assay with the midge Kiefferulus calligaster for contamination evaluation
      in aquatic agro-systems in central Thailand.
AB  - The aims of this study were to verify the suitability of in situ tests using the
      tropical midge Kiefferulus calligaster and to evaluate the most sensitive
      endpoint for the assessment of aquatic pesticide contamination. In situ tests
      were carried out in freshwater drainage channels (farm channels) that supply
      vegetable crops and receive considerable pesticide spray drift, and at channels
      outside farms (main channels). Moreover a pesticide-free farm was used as
      reference site. The endpoints analysed were: survival of the larvae, body length
      increment, capsule width increment, cholinesterase activity and glutathione S
      transferase activity. Seasonal change was investigated as rainy season and dry
      season. Deleterious effects were observed at some farms especially during the
      rainy season when farmers apply heavier doses of pesticides. However, high
      mortality rates observed in main channels suggest that these water bodies are
      also affected by other impacts besides pesticide use. This work shows the
      potential of the in situ assay with K. calligaster as a tool for the
      environmental quality assessment of tropical aquatic ecosystems.

PMID- 18331753
TI  - Microbial reduction of nitrate in the presence of nanoscale zero-valent iron.
AB  - Microbial reduction of nitrate in the presence of nanoscale zero-valent iron
      (NZVI) was evaluated to assess the feasibility of employing NZVI in the
      biological nitrate treatment. Nitrate was completely reduced within 3d in a
      nanoscale Fe(0)-cell reactor, while only 50% of the nitrate was abiotically
      reduced over 7d at 25 degrees C. The removal rate of nitrate in the integrated
      NZVI-cell system was unaffected by the presence of high amounts of sulfate.
      Efficient removal of nitrate by Fe(II)-supported anaerobic culture in 14 d
      indicated that Fe(II), which is produced during anaerobic iron corrosion in the
      Fe(0)-cell system, might act as an electron donor for nitrate. Unlike abiotic
      reduction, microbial reduction of nitrate was not significantly affected by low
      temperature conditions. This study demonstrated the potential applicability of
      employing NZVI iron as a source of electrons for biological nitrate reduction.
      Use of NZVI for microbial nitrate reduction can obviate the disadvantages
      associated with traditional biological denitrification, that relies on the use of
      organic substrates or explosive hydrogen gas, and maintain the advantages offered
      by nano-particle technology such as higher surface reactivity and functionality
      in suspensions.

PMID- 18331754
TI  - Biofiltration of trimethylamine, dimethylamine, and methylamine by immobilized
      Paracoccus sp. CP2 and Arthrobacter sp. CP1.
AB  - A biofilter using granular activated carbon with immobilized Paracoccus sp. CP2
      was applied to the elimination of 10-250 ppm of trimethylamine (TMA),
      dimethylamine (DMA), and methylamine (MA). The results indicated that the system
      effectively treated MA (>93%), DMA (>90%), and TMA (>85%) under high loading
      conditions, and the maximum degradation rates were 1.4, 1.2, and 0.9g-Nkg(-1) GAC
      d(-1). Among the three different amines treated, TMA was the most difficult to
      degrade and resulted in ammonia accumulation. Further study on TMA removal showed
      that the optimal pH was near neutral (6.0-8.0). The supply of high glucose
      (>0.1%) inhibited TMA removal, maybe due to substrate competition. However,
      complete TMA degradation was achieved under the co-immobilization of Paracoccus
      sp. CP2 and Arthrobacter sp. CP1 ( approximately 96%). Metabolite analysis
      results demonstrated that the metabolite NH(4)(+) concentrations decreased by a
      relatively small 27% while the metabolite NO(2)(-) apparently increased by
      heterotrophic nitrification of Arthrobacter sp. CP1 in the co-immobilization
      biofilter.

PMID- 18331755
TI  - Effect of Al(III) speciation on coagulation of highly turbid water.
AB  - In Taiwan, the turbidity of raw water for fresh water treatments can sometimes
      reach as high as 40000 NTU due to intensive rainfall, especially in typhoon
      seasons. In response, water works often apply large quantities of coagulants such
      as polyaluminium chloride (PACl). In this study, simulated and natural highly
      turbid water was coagulated with two PACls, a commercial product (PACl-1) and a
      laboratory product (PACl-E). The Al species distributions of PACl-1 and PACl-E
      under various pH conditions were determined, and the corresponding coagulation
      efficiency was evaluated. The PACl-E has a wider range of operational pH, while
      the efficiency of PACl-1 peaks at around neutral pH. For simulated water up to
      5000 NTU, the PACl-E was superior to PACl-1 at low dosage and in the pH range
      studied. Similar results were discovered with natural water, except that when the
      turbidity was extremely high, the coagulation efficiency of PACl-E decreased
      significantly due to the presence of large amounts of organic matter. The
      coagulation of PACl-E was closely related to the content of polycationic
      aluminium (Al(13)) while that of PACl-1 was dictated by the amount of Al(c). The
      sludge from PACl-E coagulation had better dewaterability when the optimum dosage
      was applied. The experimental results suggest that for natural water up to 5000
      NTU, PACl containing high Al(13) species is recommended for coagulation. In cases
      when the water contains high organic matter, efficient coagulation depends upon
      enmeshment by amorphous aluminium hydroxide.

PMID- 18331756
TI  - Biodegradation of mono-alkyl phthalate esters in natural sediments.
AB  - Mono-alkyl phthalate esters (MPEs) are primary metabolites of di-alkyl phthalate
      esters (DPEs), a family of industrial chemicals widely used in the production of
      soft polyvinyl chloride and a large range of other products. To better understand
      the long term fate of DPEs in the environment, we measured the biodegradation
      kinetics of eight MPEs (-ethyl, -n-butyl, -benzyl, -i-hexyl, -2-ethyl-hexyl, -n
      octyl, -i-nonyl, and -i-decyl monoesters) in marine and freshwater sediments
      collected from three locations in the Greater Vancouver area. After a lag period
      in which no apparent biodegradation occurred, all MPEs tested showed degradation
      rates in both marine and freshwater sediments at 22 degrees C with half-lives
      ranging between 16 and 39 h. Half-lives increased approximately 8-fold in
      incubations performed at 5 degrees C. Biodegradation rates did not differ between
      marine and freshwater sediments. Half-lives did not show a relationship with
      increasing alkyl chain length. We conclude that MPEs can be quickly degraded in
      natural sediments and that the similarity in MPE degradation kinetics among
      sediment types suggests a wide occurrence of nonspecific esterases in
      microorganisms from various locations, as has been reported previously.

PMID- 18331757
TI  - Overexpression of CEACAM6 in borderline and invasive mucinous ovarian neoplasms.
AB  - OBJECTIVE: Identifying markers specific for mucinous ovarian neoplasms (MON) is
      important for cancer diagnosis and surveillance, and will help improve our
      general understanding of the pathobiology of these tumors. CEACAM6 overexpression
      appears to be an early molecular event with prognostic significance in
      gastrointestinal carcinomas. Microarray analysis previously demonstrated high
      CEACAM6 overexpression in MON's and this study sought to validate this finding.
      METHODS: Western blot compared CEACAM6 expression in normal human ovarian surface
      epithelium (HOSE) and ovarian cancer cell lines. Quantitative RT-PCR (qRT-PCR)
      was performed on 75 laser-microdissected HOSE and ovarian cancer tissue samples.
      Immunohistochemistry (IHC) was performed and slides were analyzed in a semi
      quantitative manner. RESULTS: CEACAM6 was expressed in 2 of 3 mucinous cancer
      cell lines. Expression was absent in all 2 HOSE, 7 serous cancer, and 2 clear
      cell cancer cell lines. 100-fold CEACAM6 overexpression (qRT-PCR) was
      demonstrated in 13/16 (81%) borderline, low-grade, and high-grade invasive MON's,
      compared to 5/50 (10%) serous and 1/5 (20%) benign mucinous samples. CEACAM6
      expression was not different between borderline and invasive MON's (p=0.55) or
      across tumor stage (p=0.76). CEACAM6 staining was present in 24/28 (86%)
      borderline, low-grade, and high-grade invasive MON's; 13/28 (46%) exhibited
      moderate-strong staining. Neither CEACAM6 expression (p=0.36) nor staining
      intensity (p=0.51) was different between borderline and invasive MON's. None of
      the serous or benign mucinous tumors exhibited CEACAM6 staining. CONCLUSIONS:
      CEACAM6 is overexpressed in borderline and invasive MON's.

PMID- 18331758
TI  - Effect of covalent links on the structure, spectra, and redox properties of
      myeloperoxidase--a density functional study.
AB  - The enzyme myeloperoxidase shows several unusual properties compared to other
      peroxidases, e.g. a red-shifted absorption spectrum and a peroxidase activity
      towards chloride. It has been suggested that this is caused by the unusual
      covalent links between the heme group and the surrounding protein, but whether it
      is caused by the two ester links to Glu-242 and Asp-94 or the sulfonium ion
      linkage to Met-243 is unclear. To investigate these suggestions, we have used
      density functional theory to study the structure, spectra, and reduction
      potential of 25 models of myeloperoxidase in the reduced (Fe(II)) and oxidized
      (Fe(III)) states, as well as in the compound I (formally Fe(V)O) and II (Fe(IV)O
      or Fe(IV)OH) states, using appropriate models of the linkages to the Asp, Glu,
      and Met residues (including the back-bone connection between Glu-242 and Met-243)
      in varying combinations. The calculated spectral shifts indicate that both the
      ester and sulfonium linkages play a role in the spectral shift. On the other
      hand, the sulfonium linkage seems to be mainly responsible for the high positive
      reduction potential for the both ferric/ferrous and compound I/II couples of
      myeloperoxidase.

PMID- 18331759
TI  - Impairment of ascorbic acid's anti-oxidant properties in confined media: inter
      and intramolecular reactions with air and vanadate at acidic pH.
AB  - The anti-oxidant properties of L-ascorbic acid were investigated in the confined
      medium produced by a sodium bis(2-ethylhexyl)sulfosuccinate (aerosol-OT, AOT)
      self-assembled reverse micelle. Using 1H-1H NOESY (proton-proton 2D nuclear
      overhauser enhancement correlation spectroscopy) NMR spectroscopy, the location
      of ascorbic acid was investigated and found to be at the AOT-interface in
      contrast to earlier studies where the ascorbate was assumed to be in the water
      pool in these microemulsions. The reaction of ascorbic acid with oxygen was
      investigated using EPR spectroscopy. A delocalized monoanionic ascorbate radical
      was observed in microemulsions prepared from pH 5.6 stock solutions. This is in
      contrast to studies carried out in aqueous media where no radical formation was
      observed. The oxidation of ascorbic acid by aqueous V(V) was investigated in
      reverse micelles. Modest changes in the kinetic parameters were observed for this
      system compared to that in water. Details of these reactions were examined and
      can be summarized as the microemulsion solvating and stabilizing reactive
      intermediates via rate inhibition or enhancement. The inhibition of the oxidation
      is due to solvation stabilization of ascorbic acid in microemulsion media. Since
      ascorbate is a valuable marker of oxidative stress, our results suggest that
      compartmentization can modify the stabilization of the ascorbate radical and the
      changes in properties could be important in biological systems.

PMID- 18331760
TI  - Reversible inactivation of cytochrome P450 by alkaline earth metal ions:
      auxiliary metal ion induced conformation change and formation of inactive P420
      species in CYP101.
AB  - The effects of the divalent alkaline-earth metal ions (Ca2+ and Mg2+) on the
      substrate binding affinity, spin-state transition at the heme active site,
      conformational properties as well as the stability of the active form of
      cytochrome P450cam (CYP 101) have been investigated using various spectroscopic
      and kinetic methods. The divalent cations were found to have two types of effects
      on the enzyme. At the initial stage the alkaline-earth metal ion facilitated
      enhanced binding of the substrate and formation of the high-spin form of the heme
      active center of the enzyme compared to that in absence of any metal ion.
      However, analogous to many other mono-valent metal ions, the alkaline-earth metal
      ions were also less efficient than K+ in promoting the substrate binding and spin
      transition properties of the enzyme. The auxiliary metal ions were shown to cause
      small but distinct change in the circular dichroism spectra of the substrate-free
      enzyme in the visible region, indicating that the tertiary structure around the
      heme was perturbed on binding of the auxiliary metal ion to the enzyme. The
      effect of the auxiliary metal ion was found to be more prominent in the WT enzyme
      compared to the Y96F mutant of P450cam suggesting that the Tyr 96 residue plays
      an important role in mediating the effects of the auxiliary metal ions to the
      active site of the enzyme. At the second stage of interaction, the alkaline-earth
      metal ions were found to slowly convert the enzyme into an inactive P420 form,
      which could be reversibly re-activated by addition of KCl. The results have been
      discussed in the light of understanding the mechanism of inactivation of certain
      mammalian P450 enzymes by these alkaline-earth metal ions.

PMID- 18331761
TI  - Auditory processing indexed by stimulus-induced alpha desynchronization in
      children.
AB  - By means of magnetoencephalography (MEG), we investigated event-related
      synchronization and desynchronization (ERS/ERD) in auditory cortex activity,
      recorded from twelve children aged four to six years, while they passively
      listened to a violin tone and a noise-burst stimulus. Time-frequency analysis
      using Wavelet Transform was applied to single-trials of source waveforms observed
      from left and right auditory cortices. Stimulus-induced changes in non-phase
      locked activities were evident. ERS in the beta range (13-30 Hz) lasted only for
      100 ms after stimulus onset. This was followed by prominent alpha ERD, which
      showed a clear dissociation between the upper (12 Hz) and lower (8 Hz) alpha
      range in both left and right auditory cortices for both stimuli. The time courses
      of the alpha ERD (onset around 300 ms, peak at 500 ms, offset after 1500 ms) were
      similar to those previously found for older children and adults with auditory
      memory related tasks. For the violin tone only, the ERD lasted longer in the
      upper than the lower alpha band. The findings suggest that induced alpha ERD
      indexes auditory stimulus processing in children without specific cognitive task
      requirement. The left auditory cortex showed a larger and longer-lasting upper
      alpha ERD than did the right auditory cortex, likely reflecting hemispheric
      differences in maturational stages of neural oscillatory mechanisms.

PMID- 18331762
TI  - Tenth Forum on Liver Transplantation: are HIV-infected patients candidates for
      liver transplantation?

PMID- 18331763
TI  - Are HIV-infected patients candidates for liver transplantation?

PMID- 18331764
TI  - Combination therapy for chronic hepatitis B: ready for prime time?

PMID- 18331765
TI  - Impact of hepatitis B virus rtA181V/T mutants on hepatitis B treatment failure.
AB  - BACKGROUND/AIMS: Recent clinical observations reported the occurrence of amino
      acid substitutions at position 181 of the HBV polymerase, associated with a viral
      breakthrough under lamivudine or adefovir therapy. In this study, we
      characterized the main variants harboring the rtA181T/V mutation isolated from 10
      consecutive patients who developed lamivudine and/or adefovir resistance.
      METHODS: We performed a clonal analysis of the HBV polymerase gene amplified by
      PCR from serum samples during viral breakthrough. The main mutants were then
      tested after transfection of Huh7 cells for their resistance profile to
      nucleoside analogs. RESULTS: Clonal analysis revealed the co-localization on the
      same HBV genome of rtA181T/V with rtN236T, but not with rtM204V/I mutations
      following lamivudine, adefovir or lamivudine+adefovir breakthrough. In cell
      culture, the rtA181T/V mutation induced a decreased susceptibility to lamivudine
      (<10-fold), adefovir (2- to 8-fold) and tenofovir (2- to 3-fold). Interestingly,
      the association of rtA181T with rtN236T on one clinical isolate genome increased
      the resistance to these three drugs. All the tested mutants remained sensitive to
      entecavir. CONCLUSIONS: Our observations suggest that a single amino acid change
      at position rt181 may induce cross-resistance to lamivudine and adefovir. These
      data emphasize the clinical relevance of genotypic and phenotypic analysis in the
      management of antiviral drug resistance.

PMID- 18331766
TI  - Forward genetic analysis of TLR-signaling pathways: an evaluation.
AB  - Forward genetic approaches have contributed to our understanding of how the host
      senses infectious agents such as bacteria, viruses and fungi. Beginning with the
      initial discovery of Toll-like receptors (TLRs) as primary sensors involved in
      the recognition of microbial components, our laboratory has taken a forward
      genetic approach, using N-ethyl-N-nitrosourea (ENU) mutagenesis in mice, to
      decipher TLR-signaling pathways. This long term effort has helped to elucidate
      the circuitry of these pathways, identified new molecules, and disclosed new
      functions for known molecules. Here we review some of the more important insights
      developed from this approach and discuss its prospects.

PMID- 18331767
TI  - To feed or not to feed early in acute pancreatitis: still depend on severity?

PMID- 18331768
TI  - Uptake of selected PAHs from contaminated soils by rice seedlings (Oryza sativa)
      and influence of rhizosphere on PAH distribution.
AB  - The uptake of selected polycyclic aromatic hydrocarbons (PAHs) by rice (Oryza
      sativa) seedlings from spiked aged soils was investigated. When applied to soils
      aged for 4 months, naphthalene, phenanthrene, and pyrene exhibited volatilization
      loss of 98, 95, and 30%, respectively, with the remaining fraction being fixed by
      soil organic matter and/or degraded by soil microbes. In general, concentrations
      of the three PAHs in rice roots were greater than those in the shoots. The
      concentrations of root associated PHN and PYR increased proportionally with both
      soil solution and rhizosphere concentrations. PAH concentrations in shoots were
      largely independent of those in soil solution, rice roots, or rhizosphere soil.
      The relative contributions of plant uptake and plant-promoted rhizosphere
      microbial biodegradation to the total mass balance were 0.24 and 14%,
      respectively, based on PYR concentrations in rhizosphere and non-rhizosphere
      soils, the biomass of rice roots, and the dry soil weight.

PMID- 18331769
TI  - Protection of ash (Fraxinus excelsior) trees from ozone injury by ethylenediurea
      (EDU): roles of biochemical changes and decreased stomatal conductance in
      enhancement of growth.
AB  - Treatments with ethylenediurea (EDU) protect plants from ozone foliar injury, but
      the processes underlying this protection are poorly understood. Adult ash trees
      (Fraxinus excelsior), with or without foliar ozone symptoms in previous years,
      were treated with EDU at 450 ppm by gravitational trunk infusion in May-September
      2005 (32.5 ppm h AOT40). At 30-day intervals, shoot growth, gas exchange,
      chlorophyll a fluorescence, and water potential were determined. In September,
      several biochemical parameters were measured. The protective influence of EDU was
      supported by enhancement in the number of leaflets. EDU did not contribute its
      nitrogen to leaf tissue as a fertiliser, as determined from lack of difference in
      foliar N between treatments. Both biochemical (increase in ascorbate-peroxidase
      and ascorbic acid, and decrease in apoplastic hydrogen peroxide) and biophysical
      (decrease in stomatal conductance) processes regulated EDU action. As total
      ascorbic acid increased only in the asymptomatic trees, its role in alleviating
      O(3) effects on leaf growth and visible injury is controversial.

PMID- 18331770
TI  - Nitrogen dynamics of a mountain forest on dolomitic limestone--a scenario-based
      risk assessment.
AB  - The dominant nitrogen (N) fluxes were simulated in a mountain forest ecosystem on
      dolomitic bedrock in the Austrian Alps. Based on an existing small-scale climate
      model the simulation encompassed the present situation and a 50-yr projection.
      The investigated scenarios were current climate, current N deposition (SC1) and
      future climate (+2.5 degrees C and +10% annual precipitation) with three levels
      of N deposition (SC2, 3, 4). The microbially mediated N transformation, including
      the emission of nitrogen oxides, was calculated with PnET-N-DNDC. Soil hydrology
      was calculated with HYDRUS and was used to estimate the leaching of nitrate. The
      expected change of the forest ecosystem due to changes of the climate and the N
      availability was simulated with PICUS. The incentive for the project was the fact
      that forests on dolomitic limestone stock on shallow Rendzic Leptosols that are
      rich in soil organic matter are considered highly sensitive to the expected
      environmental changes. The simulation results showed a strong effect due to
      increased temperatures and to elevated levels of N deposition. The outflux of N,
      both as nitrate (6-25 kg N ha(-1)yr(-1)) and nitrogen oxides (1-2 kg N ha(-1)yr(
      1)), from the forest ecosystem are expected to increase. Temperature exerts a
      stronger effect on the N(2)O emission than the increased rate of N deposition.
      The main part of the N emission will occur as N(2) (15 kg N ha(-1)yr(-1)). The
      total N loss is partially offset by increased rates of N uptake in the biomass
      due to an increase in forest productivity.

PMID- 18331771
TI  - A directional passive air sampler for monitoring polycyclic aromatic hydrocarbons
      (PAHs) in air mass.
AB  - A passive air sampler was developed for collecting polycyclic aromatic
      hydrocarbons (PAHs) in air mass from various directions. The airflow velocity
      within the sampler was assessed for its responses to ambient wind speed and
      direction. The sampler was examined for trapped particles, evaluated
      quantitatively for influence of airflow velocity and temperature on PAH uptake,
      examined for PAH uptake kinetics, calibrated against active sampling, and finally
      tested in the field. The airflow volume passing the sampler was linearly
      proportional to ambient wind speed and sensitive to wind direction. The uptake
      rate for an individual PAH was a function of airflow velocity, temperature and
      the octanol-air partitioning coefficient of the PAH. For all PAHs with more than
      two rings, the passive sampler operated in a linear uptake phase for three weeks.
      Different PAH concentrations were obtained in air masses from different
      directions in the field test.

PMID- 18331772
TI  - Development of good modelling practice for physiologically based pharmacokinetic
      models for use in risk assessment: the first steps.
AB  - The increasing use of tissue dosimetry estimated using pharmacokinetic models in
      chemical risk assessments in various jurisdictions necessitates the development
      of internationally recognized good modelling practice (GMP). These practices
      would facilitate sharing of models and model evaluations and consistent
      applications in risk assessments. Clear descriptions of good practices for (1)
      model development i.e., research and analysis activities, (2) model
      characterization i.e., methods to describe how consistent the model is with
      biology and the strengths and limitations of available models and data, such as
      sensitivity analyses, (3) model documentation, and (4) model evaluation i.e.,
      independent review that will assist risk assessors in their decisions of whether
      and how to use the models, and also model developers to understand expectations
      for various purposes e.g., research versus application in risk assessment. Next
      steps in the development of guidance for GMP and research to improve the
      scientific basis of the models are described based on a review of the current
      status of the application of physiologically based pharmacokinetic (PBPK) models
      in risk assessments in Europe, Canada, and the United States at the International
      Workshop on the Development of GMP for PBPK Models in Greece on April 27-29,
      2007.

PMID- 18331773
TI  - Human health risk assessments for three neuropharmaceutical compounds in surface
      waters.
AB  - Enhanced sensitivity of analytical chemistry methods has enabled the detection of
      low-levels of pharmaceuticals in the environment, resulting in questions about
      the safety of surface waters used for drinking supplies. Human health risk
      assessments were performed to evaluate the risks from residues of atomoxetine,
      duloxetine, and olanzapine, which might be found in surface waters. Preclinical
      safety studies and human clinical data were used to determine an acceptable daily
      intake (ADI) for each compound: atomoxetine, 1.4 microg/kg/day; duloxetine, 1.8
      microg/kg/day; and olanzapine, 1.4 microg/kg/day. The calculated predicted no
      effect concentrations (PNECs) for children were 25.7, 19.1, and 35.9 microg/L for
      atomoxetine, duloxetine, and olanzapine, respectively. Estimated exposure
      concentrations determined using United States Food and Drug Administration
      guidelines and predicted exposure concentrations from the PhATE model were
      compared with each PNEC to determine margins of safety, which ranged from 147 to
      642. Based on currently available data used in this assessment, no appreciable
      human health risks exist from exposure to the highest 99th percentile of
      predicted residue levels of atomoxetine, duloxetine or olanzapine in surface
      waters under low-flow conditions.

PMID- 18331774
TI  - The contribution of job characteristics to socioeconomic inequalities in
      incidence of myocardial infarction.
AB  - The current study estimated the contribution of job characteristics to
      socioeconomic inequalities in incidence of myocardial infarction (MI) during a 12
      year follow-up period. Data were from the working population (aged 25-64 years)
      in the Netherlands longitudinal GLOBE study (N=5757). Self-reported information
      was available from baseline measurement (in 1991) for education, occupation, job
      demand, job control, fear of becoming unemployed, adverse physical working
      conditions, and smoking and alcohol use. Information on hospital admissions for
      MI among study participants was available until 2003, and was linked to baseline
      data via record linkage. Cox regression analyses were performed to estimate the
      hazard of MI in different socioeconomic groups before and after adjustment for
      job characteristics and health-related behaviours. Lower educated and manual
      workers had a higher risk of MI during follow-up, after adjusting for age, sex
      and marital status than higher educated and non-manual workers, respectively.
      After adjustment for occupation, the lowest educated still had an elevated risk
      of MI. After adjustment for education, no significant association of occupation
      with MI was observed. Job control and adverse physical working conditions were
      not significantly associated with MI after adjustment for socioeconomic position.
      These results suggest that the reduction of the socioeconomic position-MI
      association after adjustment for the two specific job characteristics reflect the
      effect of other unobserved factors closely related to both socioeconomic position
      and job characteristics. The results of this study point toward education as
      being the stronger predictor of hospital admitted MI, compared to occupational
      position and job characteristics, in the Dutch working population.

PMID- 18331775
TI  - Isolation and characterization of new lactam compounds that inhibit lung and
      colon cancer cells from adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) bran.
AB  - Five active compounds that inhibit cancer cells were isolated from adlay bran
      (Coix lachryma-jobi L. var. ma-yuen Stapf), and their structures and activities
      in vitro were characterized. The ethyl acetate-soluble fraction of methanol
      extracts of adlay bran (ABM-EtOAc) exhibited a stronger anti-proliferative effect
      on human lung cancer cell A549, human colorectal carcinoma cell HT-29, and COLO
      205 than other fractions by MTT (3-4,5-dimethylthiazol-2-yl-2,5-diphenyl
      tetrazolium bromide) assay. Assay-guided isolation gave five lactams including
      three that were previously undocumented; coixspirolactam A (1), coixspirolactam B
      (2), and coixspirolactam C (3); one isolated from the natural plant for the first
      time, coixlactam (4); and one known compound, methyl dioxindole-3-acetate (5).
      Pure active compounds were identified by spectral analysis including IR, 1H and
      13C NMR, UV-vis, MS and 2D NMR techniques. All the compounds were tested for
      their anti-proliferative effect on A549, HT-29 and COLO 205 cells. These
      compounds showed anti-cancer activities with IC50 values between 28.6 and
      72.6microg/mL.

PMID- 18331776
TI  - Flavones and flavonols exert cytotoxic effects on a human oesophageal
      adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis.
AB  - Dietary flavonoids have been shown to exert specific cytotoxicity towards some
      cancer cells, but the precise molecular mechanisms are still not completely
      understood. In our study, cytotoxic effects of structurally related flavones and
      flavonols on a human oesophageal adenocarcinoma cell line (OE33) were compared,
      and the molecular mechanisms responsible for their cytotoxic effects were
      explored. The results of MTT assay showed that flavones (luteolin, apigenin,
      chrysin) and flavonols (quercetin, kaempferol, myricetin) were all able to induce
      cytotoxicity in OE33 cells in a dose- and time-dependent manner, and the
      cytotoxic potency of these compounds was in the order of
      quercetin>luteolin>chrysin>kaempferol>apigenin>myricetin. Flow cytometry and DNA
      fragmentation analysis indicated that the cytotoxicity induced by flavones and
      flavonols was mediated by G2/M cell cycle arrest and apoptosis. Furthermore, the
      expression of genes related to cell cycle arrest and apoptosis was assessed by
      oligonucleotide microarray, real-time RT-PCR and Western blot. It was found that
      the treatment of OE33 cells with flavones and flavonols caused G2/M arrest
      through up-regulation of GADD45beta and 14-3-3sigma and down-regulation of cyclin
      B1 at the mRNA and protein levels, and induced p53-independent mitochondrial
      mediated apoptosis through up-regulation of PIG3 and cleavage of caspase-9 and
      caspase-3. The results of western blot analysis further showed that increases of
      p63 and p73 protein translation or stability might be contribute to the
      regulation of GADD45beta, 14-3-3sigma, cyclin B1 and PIG3.

PMID- 18331777
TI  - Factors determining copper concentration in tea leaves produced at Yuyao County,
      China.
AB  - Over consumption of copper (Cu) from food and beverages is detrimental to human
      health. In this study, we investigated Cu accumulation in tea leaves produced in
      Yuyao County in China. Copper concentrations in all tea leaves sampled from tea
      gardens were below 60mgkg(-1), the permissible level given by the Chinese
      Ministry of Health; however, 15% of the samples were over 15mgkg(-1), the
      allowable level of 'green food' as defined by the Chinese Ministry of
      Agriculture. These observations indicate that Cu concentrations in tea leaves
      from the investigated producing areas are acceptable, but still a concern. To
      understand what factors affect the Cu accumulation in the tea leaves, we further
      analyzed soils from the tea gardens for Cu availability, pH and organic matter
      content. The Cu availability in soil was found to be closely correlated with the
      soil's H+ activity, followed by organic matter content. The soils in the tea
      gardens were also found to be severely acidic with the lowest pH of 3.58. The tea
      garden soils, if fertilized with animal manure, could also contribute to the risk
      of Cu contamination. Additionally, Cu concentrations in the final products of tea
      leaves were greatly increased by the machinery processing in factories that used
      copper boards at the twisting stage. In one factory, the Cu level was increased
      by 32.1mgkg(-1). This study suggests that both edaphic and non-edaphic factors
      can contribute to the final Cu accumulation in tea leaves used by consumers.

PMID- 18331778
TI  - Carcinogenic risk of heterocyclic amines in combination - assessment with a liver
      initiation model.
AB  - Carcinogenic potential of heterocyclic amines (HCAs) was investigated using an in
      vivo 5-week initiation assay with quantitative evaluation of glutathione S
      transferase placental form (GST-P) positive foci in rat liver. Numbers of GST-P
      positive foci were significantly increased with individual administration of six
      different HCAs, indicating utility of the assay. It was therefore applied to
      investigate risk with multiple HCAs in combination. Unexpectedly, concomitant
      treatment with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino
      3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) did not result in any additive
      carcinogenicity. In the rats taking MeIQx prior to PhIP the value was almost
      equal to the sum total of individual data, indicating additive initiation
      activities. In contrast, simultaneous or prior administration of PhIP rather
      exerted inhibitory effects on the carcinogenic potential of MeIQx. Moreover,
      microarray and quantitative RT-PCR assessment revealed that PhIP induced
      cytochrome P450 1A1, responsible for both activation and detoxification of HCAs,
      more strongly than MeIQx. It is noteworthy that complex exposure to multiple HCAs
      is not necessarily associated with increased risk of carcinogenesis because they
      are simultaneously and continuously ingested under normal circumstances.

PMID- 18331779
TI  - Genomic instability, mutations and expression analysis of the tumour suppressor
      genes p14(ARF), p15(INK4b), p16(INK4a) and p53 in actinic keratosis.
AB  - Actinic keratosis (AK) is a well-established pre-cancerous skin lesion that has
      the potential to progress to squamous cell carcinoma (SCC). We investigated the
      involvement of the CDKN2A, CDKN2B and p53 genes in AK and in the progression of
      AK to SCC. Mutational analysis on exons 1a, 1b and 2 of the CDKN2A locus and exon
      1 of the CDKN2B locus as well as allelic imbalance was performed in 26 AK
      specimens. Expression levels of the genes p14(ARF), p15(INK4b), p16(INK4a) and
      p53 were examined in 16 AKs and 12 SCCs by real-time RT-PCR. A previously
      described polymorphism of p16(INK4a) (Ala148Thr) was detected at an allelic
      frequency of 12%. Six samples carried novel mutations at codon 71 of the CDKN2A
      locus and one sample presented an additional mutation at codon 65. Two AK samples
      carried a not-previously described non-UV type missense mutation at codon 184
      (Val184Glu) of exon 1b in the p14(ARF) gene. Regarding the CDKN2B locus a new
      mutation at codon 50 (Ala50Thr) and another at codon 24 (Arg24Arg), were
      detected. Microsatellite instability (MSI) was found in 15% of AKs in at least
      one marker, indicating that genetic instability has some implication in the
      development of AK. Down-regulation of p16(INK4a) and p53 mRNA levels was noted in
      SCC compared to AK. TSGs expression levels in sun-exposed morphologically normal
      appearing skin, suggests that abnormal growth stimuli might exist in these
      tissues as well. Furthermore, we suggest a possible role of p15(INK4b),
      independently from the intracellular pathway mediated by p16(INK4a), and of
      p14(ARF) in AK development, as well as in the progression of AK to SCC. The
      deregulation of the expression profiles of the CDKN2A, CDKN2B and p53 genes may,
      independently of mutations and LOH at 9p21, play a significant role in AK and
      progression of AK to SCC.

PMID- 18331780
TI  - Retigabine, the specific KCNQ channel opener, blocks ectopic discharges in
      axotomized sensory fibres.
AB  - The M-current has been proposed as a potential target for analgesia under
      neuropathic pain conditions. M-currents and/or their molecular correlates, KCNQ
      proteins, have been demonstrated in key elements of the nociceptive system
      including spinal and dorsal root ganglion neurons. Here we demonstrate that
      retigabine, a selective KCNQ channel opener, applied at neuromatose endings
      modulates the excitability of axotomized fibres inhibiting ectopic discharges.
      Responses to mechanical and chemical stimulation were obtained from intact and
      previously axotomized Adelta- and C-fibres using in vitro preparations and
      extracellular electrophysiological recording techniques. Application of
      retigabine (10 microM) produced an estimated approximately 80% reduction in the
      number of discharges produced by mechanical and chemical stimulation of most
      axotomized fibres tested (24/27). The electrical threshold of stimuli applied to
      the neuroma was found to increase in the presence of retigabine (+17.5+/-2.3%)
      and to decrease in the presence of a high potassium medium (-16.5+/-3.7%). This
      indicates that retigabine produces a hyperpolarization and a subsequent reduction
      of the excitability in aberrant sensory endings. Application of XE-991 (10
      microM), a KCNQ channel blocker, had no effect on responses to stimulation of the
      neuroma but blocked the effects of retigabine indicating a specific involvement
      of KCNQ channels. In contrast to the strong effects on ectopic discharges,
      retigabine did not change responses to stimulation recorded from intact
      receptors. Results indicate that KCNQ channel opening at axotomized endings may
      constitute a novel and selective mechanism for modulation of some neuropathic
      pain symptoms.

PMID- 18331781
TI  - Chronic hypoxia-hypercapnia influences cognitive function: a possible new model
      of cognitive dysfunction in chronic obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) is a slowly progressive lung disease
      that results in several complications, including cognitive dysfunction. Some
      evidences support that cognitive impairment is common and clinically important in
      COPD, but the exact mechanism is still unclear. It has been confirmed that
      chronic hypoxia-hypercapnia contributes a lot to the development in
      pathophysiology of COPD. Data from some pilot studies indicated that chronic
      hypoxia-hypercapnia influences cognitive functions both in patients and in
      animals, which includes some distinctive pattern of cognitive dysfunction in
      human being or impairment of spatial learning-memory in rat. Therefore, we
      propose that cognitive impairment is strongly related to combination of chronic
      hypoxia and hypercapnia, and chronic hypoxia-hypercapnia-induced animal models
      may mimic the cognitive dysfunction of COPD. Attempts to confirm this hypothesis
      may lead to new model of cognitive dysfunction in COPD.

PMID- 18331783
TI  - Antitrypsin activity of extracts from Ecballium elaterium seeds.
AB  - The antitrypsin activity of extracts obtained from two different seed types of
      Ecballium elaterium, was tested in vitro. The presence of trypsin inhibitors in
      three chromatographed samples for each extract, showed a strong and specific
      antitrypsin activity.

PMID- 18331782
TI  - The planetary biology of ascorbate and uric acid and their relationship with the
      epidemic of obesity and cardiovascular disease.
AB  - Humans have relatively low plasma ascorbate levels and high serum uric acid
      levels compared to most mammals due to the presence of genetic mutations in l
      gulonolactone oxidase and uricase, respectively. We review the major hypotheses
      for why these mutations may have occurred. In particular, we suggest that both
      mutations may have provided a survival advantage to early primates by helping
      maintain blood pressure during periods of dietary change and environmental
      stress. We further propose that these mutations have the inadvertent disadvantage
      of increasing our risk for hypertension and cardiovascular disease in today's
      society characterized by Western diet and increasing physical inactivity.
      Finally, we suggest that a "planetary biology" approach in which genetic changes
      are analyzed in relation to their biological action and historical context may
      provide the ideal approach towards understanding the biology of the past, present
      and future.

PMID- 18331784
TI  - Clinical significance of LAMB3 and COL7A1 mRNA in esophageal squamous cell
      carcinoma.
AB  - AIMS: LAMB3 and COL7A1 genes code for the laminin-5beta3 chain and type VII
      collagen, respectively. They constitute the major components of the basement
      membrane zone. The aim of the current study was to clarify the clinical
      significance of LAMB3 and COL7A1 mRNA expression in esophageal squamous cell
      carcinoma (ESC). METHODS: We quantitated the expression of LAMB3 mRNA and COL7A1
      mRNA in malignant esophageal tissues (T) and corresponding normal tissues (N) by
      real-time quantitative reverse transcription-polymerase chain reaction assays.
      The clinicopathologic significance of LAMB3 and COL7A1 expression was also
      determined. Paired T and N tissues were obtained from 66 patients who underwent
      curative esophagectomy. RESULTS: The expression levels of LAMB3 and COL7A1 mRNAs
      were higher in malignant tissues than in the corresponding normal tissues. The
      level of LAMB3 expression was significantly correlated with the depth of invasion
      and venous invasion (p=0.007 and 0.001, respectively). COL7A1 expression was
      significantly correlated with depth of tumor invasion and lymphatic invasion
      (p=0.046, 0.013, respectively). The five-year survival rate was better in the 22
      patients with relatively low expression of both LAMB3 and COL7A1 in comparison
      with the other 44 cases (p<0.05). CONCLUSION: The evaluation of LAMB3 and COL7A1
      mRNA expression is useful for predicting the malignant properties of ESC and may
      prove valuable in predicting the future course of the disease.

PMID- 18331785
TI  - Social management of LPS-induced inflammation in Formica polyctena ants.
AB  - Invertebrates, and especially insects, constitute valuable and convenient models
      for the study of the evolutionary roots of immune-related behaviors. With stable
      conditions in the nest, high population densities, and frequent interactions,
      social insects such as ants provide an excellent system for examining the spread
      of pathogens. The evolutionary success of these species raises questions about
      the behavioral responses of social insects to an infected nestmate. In this
      experiment, we tested the behavioral changes of the red wood ant Formica
      polyctena toward an immune-stimulated nestmate. We used bacterial endotoxin
      (lipopolysaccharides, LPS) to active the innate immune system of individual
      worker ants without biasing our observation with possible cues or host
      manipulation from a living pathogen. We show that LPS-induced immune activation
      in ants triggers behavioral changes in nestmates. Contrary to what would be
      expected, we did not find removal strategies (e.g. agonistic behaviors) or
      avoidance of the pathogenic source, but rather a balance between a limitation of
      pathogen dissemination (i.e. decreased trophallaxis and locomotion of the LPS
      treated ant), and what could constitute the behavioral basis for a "social
      vaccination" (i.e. increased grooming). This supports the importance of social
      interactions in resistance to disease in social insects, and perhaps social
      animals in general.

PMID- 18331786
TI  - The role of 20-hydroxyecdysone and juvenile hormone in pupal commitment of the
      epidermis of the silkworm, Bombyx mori.
AB  - During the pupal metamorphosis in insects, cellular commitment for pupal
      differentiation must precede before its differentiation. The pupal commitment of
      Bombyx mori epidermis occurred from day 3 to day 6 last (5th) instar larvae in
      response to the gradual increase in ecdysteroid titer in the presence of a small
      amount of juvenile hormone (JH). Yet the concealed preparatory process of the
      commitment had begun in the newly synthesized 5th instar larval epidermis
      (approximately 6 h before the ecdysis) as a competence phase, in which pupal
      commitment in vitro was induced by 20-hydroxyecdysone (20E) but inhibited by JH.
      This competence phase continued until day 2 5th instar, and the decrease and
      increase in cellular sensitivity to JH and 20E, respectively, occurred gradually
      during this period. In early day 3, autonomous pupal commitment began in vitro
      and 20E stimulated the commitment, but JH could only partially prevent the
      commitment in both cases. This apparent reversible to irreversible transition
      ended in early day 6 by the completion of pupal commitment, when the cells
      completely lost their sensitivity to JH and no longer expressed the larval
      cuticle protein gene 30. The expression of the transcription factor, broad,
      closely followed the commitment, so that we could use this gene expression as a
      molecular marker for pupal commitment. These results indicate that exposure to
      20E and loss of the sensitivity of the epidermal cells to JH are required for the
      completion of pupal commitment, and suggest that the unusually long process over
      3 days could be due to the presence of the detectable JH during the commitment.

PMID- 18331787
TI  - Sewage sludge ash to phosphorus fertiliser: variables influencing heavy metal
      removal during thermochemical treatment.
AB  - The aim of this study was to improve the removal of heavy metals from sewage
      sludge ash by a thermochemical process. The resulting detoxified ash was intended
      for use as a raw material rich in phosphorus (P) for inorganic fertiliser
      production. The thermochemical treatment was performed in a rotary kiln where the
      evaporation of relevant heavy metals was enhanced by additives. The four
      variables investigated for process optimisation were treatment temperature, type
      of additive (KCl, MgCl(2)) and its amount, as well as type of reactor (directly
      or indirectly heated rotary kiln). The removal rates of Cd, Cr, Cu, Ni, Pb, Zn
      and of Ca, P and Cl were investigated. The best overall removal efficiency for
      Cd, Cu, Pb and Zn could be found for the indirectly heated system. The type of
      additive was critical, since MgCl(2) favours Zn- over Cu-removal, while KCl acts
      conversely. The use of MgCl(2) caused less particle abrasion from the pellets in
      the kiln than KCl. In the case of the additive KCl, liquid KCl - temporarily
      formed in the pellets - acted as a barrier to heavy metal evaporation as long as
      treatment temperatures were not sufficiently high to enhance its reaction or
      evaporation.

PMID- 18331788
TI  - Pegylated liposomal doxorubicin-associated hand-foot syndrome: recommendations of
      an international panel of experts.
AB  - BACKGROUND: Hand-foot syndrome (HFS) is dose-limiting and the most common
      cumulative toxicity associated with pegylated liposomal doxorubicin (PLD). It can
      cause considerable discomfort and lead to therapy interruption. Numerous
      approaches to HFS management have been reported, but there is no consensus.
      METHODS: Published literature (identified via Medline and internet search) and
      expert experience regarding HFS and its pathogenesis, incidence, risk factors,
      prevention and treatment in patients undergoing treatment with PLD were collected
      and reviewed by a panel of experts. A consensus technique was used to develop
      recommendations. FINDINGS: The pathogenesis of PLD-associated HFS has been
      recently elucidated. Systems used to grade, prevent and treat HFS in individuals
      treated with PLD vary widely. A randomised clinical study demonstrated that PLD
      dose intensity reduction can prevent HFS. While there is limited literature
      support, patient education and supportive measures were endorsed by the expert
      panel as effective strategies for HFS prevention and treatment. An easy to use
      HFS grading and management algorithm was developed, early signs and symptoms of
      HFS outlined and specific recommendations for supportive care developed.
      INTERPRETATION: The paucity of data on the management of PLD-associated HFS led
      the expert panel to develop consensus-based recommendations. Patient education
      and supportive measures are important elements in the management of HFS and dose
      intensity reduction has documented efficacy in prevention. At a PLD dose
      intensity not exceeding 10mg/m(2) weekly, HFS can be easily managed. Phase III
      research to support the efficacy other interventions is lacking.

PMID- 18331789
TI  - Changes in soil properties and in the growth of Lolium multiflorum in an acid
      soil amended with a solid waste from wineries.
AB  - The agronomic utility of a solid waste, waste perlite (WP), from wine companies
      was assessed. In this sense, the natural characteristics of the waste were
      measured, followed by the monitoring of its effects on the chemical properties of
      acid soils and the growth of Lolium multiflorum. Taking into account that heavy
      metals associated to the waste (such as Cu, Zn and Mn) could cause problems when
      used as amendment, the changes in their total levels and in their soil
      fractionation were also studied, together with their total contents in L.
      multiflorum. The high content in C (214gkg(-1)), N (25gkg(-1)), P (534mgkg(-1))
      and K (106gkg(-1)) of WP turned it into an appropriate amendment to increase soil
      fertility, solving at the same time its disposal. WP contributed to increase soil
      pH (in 2 pH units) and cation exchange capacity (CEC increased in 3cmolckg(
      1)units), but reduced the potential Cu phytotoxicity due to a change in Cu
      distribution towards less soluble fractions. The growth of L. multiflorum
      adequately responds to the treatment with WP at addition rates below 2.5gkg(-1),
      whereas the imbalance between nutrients can justify the reduction in biomass
      production at higher WP addition rates. The levels of heavy metals analyzed in L.
      multiflorum biomass (8-85gkg(-1)) do not seem to cause undesirable effects on its
      growth.

PMID- 18331790
TI  - Identification and purification of the main components of cellulases from a
      mutant strain of Trichoderma viride T 100-14.
AB  - A new mutant strain of fungus Trichoderma viride T 100-14 was cultivated on 1%
      microcrystalline cellulose (Avicel) for 120h and the resulting culture filtrate
      was prepared for protein identification and purification. To identify the
      predominant catalytic components, cellulases were separated by an adapted two
      dimensional electrophoresis technique. The apparent major spots were identified
      by high performance liquid chromatography electrospray ionization mass (HPLC-ESI
      MS). Seven of the components were previously known, i.e., the endoglucanases
      Cel7B (EG I), Cel12A (EG III), Cel61A (EG IV), the cellobiohydrolases Cel7A (CBH
      I), Cel6A (CBH II), Cel6B (CBH IIb) and the beta-glucosidase. The seven major
      components in the fermentation broth of T. viride T 100-14 probably constitute
      the essential enzymes for crystalline cellulose hydrolysis and they were further
      purified to electrophoretic homogeneity by a series of chromatography column.
      Hydrolysis studies of the purified elements revealed that three of the cellulases
      were classified as cellobiohydrolases due to their main activities on p
      nitrophenyl-beta-d-cellobioside (pNPC). Three of the cellulases, with the
      abilities of hydrolyzing both carboxymethyl-cellulose (CMC) and Avicel indicate
      their endoglucanase activities. It deserved noting that the beta-glucosidase from
      the T 100-14 displayed an extremely high activity on p-nitrophenyl-beta-D
      glycopyranoside (pNPG), which suggested it was a good candidate for the
      conversion of cellobiose to glucose.

PMID- 18331791
TI  - The role of earthworm Lampito mauritii (Kinberg) in amending lead and zinc
      treated soil.
AB  - A laboratory experiment was carried out to determine the effect of earthworm
      (Lampito mauritii) activity on mobility of Pb2+ and Zn2+ in the soil (DTPA
      extractable) and its composting potential in presence of these metals. Well
      clitellate earthworms collected from an uncontaminated site were exposed to
      different concentrations (75, 150, 300mgkg(-1)) of Pb2+ and Zn2+ separately for
      30 days. It was observed that the metal burden in the earthworm tissue increased
      with the increase in metal treatment. L. mauritii elevated the soil pH of all the
      metal treated beds and lowered the soil C/N ratio in the cast by reducing the
      organic carbon and fixing additional nitrogen. Earthworm activity significantly
      increased the availability of phosphorous, potassium and decreased the amount of
      DTPA-extractable Pb2+ and Zn2+ in the cast, which implies the immobilization of
      metals in soils. These findings suggest the use of L. mauritii in amelioration of
      metal contaminated soil.

PMID- 18331792
TI  - Degradation of acetochlor by four microbial communities.
AB  - Four microbial communities capable of degrading acetochlor, designated A, D, E,
      and J, were obtained from acetochlor-contaminated soil and sludge. Acetochlor at
      an initial concentration of 55mg/L was completely degraded by the four mixed
      cultures after 4 days. At 80 mg/L acetochlor, more than 99% degradation was
      observed with D, 84% with A and E, and 88% with J after 9 days. There are primary
      eight strains of bacteria in community A, three in community D, E, and J,
      respectively. No single isolate was able to degrade acetochlor efficiently. The
      acetochlor biodegradation products were identified by gas chromatography-mass
      spectrometry. The probable degradative pathways of acetochlor involved
      dechlorination, hydroxylation, deethoxymethylation, cyclization, carboxylation,
      and decarboxylation. Propachlor, alachlor, and metolachlor, which are also the
      main components of the chloroacetanilide herbicide, could be degraded by the four
      mixed cultures to some degree. Given the high degradation rates observed here,
      the four mixed cultures obtained may be useful in the degradation processes of
      acetochlor.

PMID- 18331793
TI  - Is sludge retention time a decisive factor for aerobic granulation in SBR?
AB  - This study investigated the role of sludge retention time (SRT) in aerobic
      granulation under negligible hydraulic selection pressure. Results showed that no
      successful aerobic granulation was observed at the studied SRTs in the range of 3
      40 days. A comparison analysis revealed that hydraulic selection pressure in
      terms of the minimum settling velocity would be much more effective than SRT for
      enhancing heterotrophic aerobic granulation in sequencing batch reactor (SBR). It
      was shown that SRT would not be a decisive factor for aerobic granulation in SBR.

PMID- 18331794
TI  - Selective cell adhesion inhibitors: Barbituric acid based alpha4beta7--MAdCAM
      inhibitors.
AB  - A novel series of barbituric acid derivatives were identified as selective
      inhibitors of alpha4beta7 MAdCAM (mucosal addressin cell adhesion molecule-1)
      interactions via a high throughput screening exercise. These inhibitors were
      optimized to submicromolar potencies in whole cell adhesion assays, retaining
      their selectivity over alpha4beta1 VCAM.

PMID- 18331795
TI  - Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors.
AB  - The synthesis, selectivity, rat pharmacokinetic profile, and drug metabolism
      profiles of a series of potent fluoroolefin-derived DPP-4 inhibitors (4) are
      reported. A radiolabeled fluoroolefin 33 was shown to possess a high propensity
      to form reactive metabolites, thus revealing a potential liability for this class
      of DPP-4 inhibitors.

PMID- 18331796
TI  - Synthesis and biological activities of 2-oxocycloalkylsulfonamides.
AB  - A series of novel 2-oxocycloalkylsulfonamides (4) were synthesized and their
      structures confirmed by IR, (1)H NMR, and elemental analysis. The bioassay showed
      that they have fair to excellent fungicidal activities against Botrytis cinerea
      Pers and Sclerotinia sclerotiorum. Among them, compounds 4A(10), 4A(11), 4A(12),
      4B(2), and 4B(3), the EC(50) values of which were 2.12, 3.66, 3.96, 2.38, and
      2.43 microg/mL, respectively, displayed excellent fungicidal activity against B.
      cinerea Pers, and are comparable with commercial fungicide procymidone (the
      EC(50) value is 2.45 microg/mL). 3D QSAR against B. cinerea Pers was studied, a
      statistically significant and chemically meaningful CoMFA model was developed and
      some compounds which have a high predicted activity were forecasted. In addition,
      the bioassay also showed that the compounds have good inhibitory activities
      against human tumor cells HL-60, BGC-823, Bel-7402 and KB. It is interesting to
      point out that the antitumor activities of compounds 4 are in accordance with
      their fungicidal activity to a great extent: compounds having relatively best
      antitumor activities (4A(10), 4A(11), 4A(12), and 4B(3)) also displayed excellent
      fungicidal activity.

PMID- 18331797
TI  - Labeling, characterization, and in vivo localization of a new 90Y-based
      phosphonate chelate 2,3-dicarboxypropane-1,1-diphosphonic acid for the treatment
      of bone metastases: Comparison with 99mTc-DPD complex.
AB  - The goal of this investigation was to examine the possibilities for yttrium-90
      labeling of the 2,3-dicarboxypropane-1,1-diphosphonic acid (DPD), which is
      currently labeled with technetium-99m and as a (99m)Tc-DPD clinically used as
      bone imaging agent. Analysis of the complex enclosed the radiochemical quality
      control methods, biodistribution studies, as well as the determination of
      pharmacokinetic parameters. The biological behavior of complexes (90)Y-DPD,
      (99m)Tc-DPD and (90)Y-labeled DPD-kit formulation [(90)Y-(Sn)-DPD] in animal
      model was compared. The labeling conditions were standardized to give the maximum
      yield, which ranged between 93% and 98%. The examined (90)Y complex could be
      easily prepared, with an outstanding yield and was also found to be very stable
      for at least 10h after (90)Y-labeling. Protein binding value was 4.6+/-0.7% for
      (90)Y-DPD complex and the complex possess a hydrophilic character. The
      satisfactory results of (90)Y-DPD biodistribution in healthy test animals were
      obtained; the uptake in the bone was 11-13%ID/g after 24h depending on the pH
      value during the preparation. With high skeletal uptake, a minimum uptake in soft
      tissues and rapid blood clearance the (90)Y-DPD complex proved to be an excellent
      candidate for targeting tumor therapy.

PMID- 18331798
TI  - Tumor necrosis factor alpha mediates the lethal hepatotoxic effects of poly(I:C)
      in D-galactosamine-sensitized mice.
AB  - Conserved molecular patterns of microbial pathogens, such as lipopolysaccharide
      (LPS) and cytosine-phosphate-guanine (CpG) DNA motifs are important signals for
      receptor-mediated activation of innate immune cells. It has been shown that the
      liver-specific transcription-blocking d-galactosamine (D-GalN) severely
      sensitizes to the lethal effects of LPS and CpG DNA. Lethality of LPS or CpG DNA
      in GalN-treated mice is entirely due to TNF-alpha, which leads to liver cell
      apoptosis and acute liver failure. We report that also polyinosinic-polycytidylic
      acid [poly(I:C)], a TLR-3 agonist, induces systemic TNF in mice. The increases of
      hepatic enzymes and induction of death induced by LPS, CpG DNA, and poly(I:C) in
      D-GalN sensitized mice are completely blocked by neutralizing anti-TNF-alpha
      antibodies and absent in TNF receptor p55-knockout mice. Our results provide
      direct evidence that poly(I:C) induces TNF-alpha in d-GalN sensitized mice, which
      leads to severe, acute, and TNF-dependent lethal hepatitis.

PMID- 18331799
TI  - Cloning, expression, purification and characterization of recombinant glutathione
      S-transferase from Xylella fastidiosa.
AB  - Xylella fastidiosa is an important pathogen bacterium transmitted by xylem
      feedings leafhoppers that colonizes the xylem of plants and causes diseases on
      several important crops including citrus variegated chlorosis (CVC) in orange and
      lime trees. Glutathione-S-transferases (GST) form a group of multifunctional
      isoenzymes that catalyzes both glutathione (GSH)-dependent conjugation and
      reduction reactions involved in the cellular detoxification of xenobiotic and
      endobiotic compounds. GSTs are the major detoxification enzymes found in the
      intracellular space and mainly in the cytosol from prokaryotes to mammals, and
      may be involved in the regulation of stress-activated signals by suppressing
      apoptosis signal-regulating kinase 1. In this study, we describe the cloning of
      the glutathione-S-transferase from X. fastidiosa into pET-28a(+) vector, its
      expression in Escherichia coli, purification and initial structural
      characterization. The purification of recombinant xfGST (rxfGST) to near
      homogeneity was achieved using affinity chromatography and size-exclusion
      chromatography (SEC). SEC demonstrated that rxfGST is a homodimer in solution.
      The secondary and tertiary structures of recombinant protein were analyzed by
      circular dichroism and fluorescence spectroscopy, respectively. The enzyme was
      assayed for activity and the results taken together indicated that rxfGST is a
      stable molecule, correctly folded, and highly active. Several members of the GST
      family have been extensively studied. However, xfGST is part of a less-studied
      subfamily which yet has not been structurally and biochemically characterized. In
      addition, these studies should provide a useful basis for future studies and
      biotechnological approaches of rxfGST.

PMID- 18331800
TI  - Changes in the medial-lateral hamstring activation ratio with foot rotation
      during lower limb exercise.
AB  - This paper investigated whether the ratio of medial-lateral hamstring muscular
      activation could be altered with changes in foot rotation position (both internal
      and external rotation) during three standard lower limb exercises. It has been
      suggested that those with medial compartment knee OA activate the lateral
      hamstrings more than the medial to help unload the diseased compartment;
      therefore, preferential activation of this muscle during lower limb exercise may
      help to further decrease the stresses on the articular cartilage and be an
      effective intervention for knee OA and lateral hamstring injury. Thirteen healthy
      young adult subjects were tested and average medial and lateral hamstring EMG
      data during the full exercise, as well as the concentric and eccentric phases,
      were used to calculate the medial-lateral (M-L) hamstring activation ratio for
      each exercise and foot position. Results suggest that internal foot rotation
      increases the M-L hamstring activation ratio while external foot rotation
      decreases this ratio. Therefore, altering the position of the foot during
      standard lower limb exercise can help selectively activate the medial or lateral
      hamstring muscle groups. This selective activation may have implication in
      treating symptoms of knee osteoarthritis and hamstring injury; but, longitudinal
      intervention studies would be needed to determine clinical utility.

PMID- 18331801
TI  - Neural correlates of subliminal and supraliminal letter processing--an event
      related fMRI study.
AB  - One problem of interpreting research on subconscious processing is the
      possibility that participants are weakly conscious of the stimuli. Here, we
      compared the fMRI BOLD response in healthy adults to clearly visible single
      letters (supraliminal presentation) with the response to letters presented in the
      absence of any behavioural evidence of visibility (subliminal presentation). No
      letter catch trials served as a control condition. Forced-choice responses did
      not differ from chance when letter-to-background contrast was low, whereas they
      were almost 100% correct when contrast was high. A comparison of fMRI BOLD
      signals for supraliminal and subliminal letters with the control trials revealed
      a signal increase in left BA 37 (fusiform gyrus). Comparison of supraliminal with
      subliminal letters showed a significant increase in the right inferior frontal
      gyrus (BA 44, partly extending to BA 9 and BA 45, as well as BA 46). Finally, a
      comparison of subliminal with supraliminal letters showed increases in the left
      middle temporal gyrus (BA 21) and the right extrastriate cortex (BA 19).

PMID- 18331802
TI  - Reproductive isolation among cryptic species in the ectomycorrhizal genus
      Strobilomyces: population-level CAPS marker-based genetic analysis.
AB  - Among the higher fungi, reproductively isolated cryptic species exist that are
      morphologically difficult to distinguish owing to a lack of taxonomically useful
      morphological characters. Mating tests are helpful for detecting reproductive
      isolation between cryptic species, but are often difficult to perform for higher
      fungi, especially ectomycorrhizal fungi. In order to identify cryptic species of
      the ectomycorrhizal genus Strobilomyces more efficiently, lineages were defined
      based on the nucleotide sequence of two mitochondrial genes. Then the gene flow
      among lineages was measured using cleaved amplified polymorphic sequences (CAPS)
      markers designed for single copy nuclear genes. No heterozygosity was observed
      between different lineages, but within the same lineage heterozygosity was
      present at the ratio expected given Hardy Weinberg equilibrium. These results
      show that the mtDNA lineages are separate Mendelian populations, possibly cryptic
      species that are reproductively isolated from each other.

PMID- 18331803
TI  - Effects of moderate chronic ethanol consumption on hippocampal nicotinic
      receptors and associative learning.
AB  - A number of studies have reported that ethanol exposure induces changes in
      different brain systems. The hippocampus is a brain region that is very
      vulnerable to ethanol exposition, which functionally results in impairment of
      learning and memory processes reported in heavy drinkers. Hippocampal nicotinic
      receptors are involved in learning and memory. In this study, we determined the
      effects of ethanol on the main hippocampal subtypes of neural nicotinic receptors
      (alpha7 and alpha4beta2) in rats non-selected for alcohol consumption, in order
      to check for possible changes on these receptors that could be linked with
      alterations in learning acquisition. Binding assays were carried out with
      [3H]methyllycaconitine ([3H]MLA) to study the alpha7 and [3H]nicotine to study
      alpha4beta2 receptors. Auto-shaping, continuous ratio and extinction procedures
      were used as behavioral tests. The results show that moderate chronic ethanol
      consumption for 10 weeks produces: (a) a decrease of both hippocampal nicotinic
      receptor subtypes without alterations in affinity; (b) no differences in
      behavioral performance between control rats and ethanol-drinking rats in auto
      shaping and continuous ratio; (c) an improvement of performance of extinction
      paradigm. These results indicate that chronic ethanol consumption, at moderate
      levels, induces changes in hippocampal nicotinic receptors but does not impair
      acquisition and performance of new associative learning and even improves some
      kind of paradigms. These results may have implications in the biochemical basis
      of interactions between alcohol and nicotine and the effects of these drugs on
      behavior.

PMID- 18331804
TI  - Chronic, but not acute, tricyclic antidepressant treatment alleviates neuropathic
      allodynia after sciatic nerve cuffing in mice.
AB  - Antidepressant drugs act mainly by blocking the noradrenaline and/or serotonin
      uptake sites and require a chronic treatment. Tricyclic antidepressants are among
      the first line treatments clinically recommended against neuropathic pain. As
      observed against depression, a chronic treatment is required for a therapeutic
      effect. However, both in depression-related and pain-related research in rodents,
      it is difficult to design models that reproduce the clinical conditions and are
      sensitive to chronic but not to acute treatment by antidepressant drugs. In this
      study, we used a murine neuropathic pain model induced by the unilateral
      insertion of a polyethylene cuff around the main branch of the sciatic nerve.
      This model induced a long-lasting ipsilateral mechanical allodynia. We evidenced
      that chronic, but not acute, treatment with the tricyclic antidepressants
      nortriptyline or amitriptyline suppressed the cuff-induced mechanical allodynia.
      On the contrary, fluoxetine, a selective serotonin reuptake inhibitor, remained
      ineffective. To understand which mechanism is recruited downstream in order to
      alleviate the allodynia, we tested the opioid receptor antagonist naloxone, the
      delta-opioid receptor antagonist naltrindole and the kappa-opioid receptor
      antagonist nor-BNI. We show that the therapeutic effect of notriptyline
      implicates the endogenous opioid system, in particular the delta- and the kappa
      opioid receptors. For comparison, we tested the anticonvulsant gabapentin and
      showed that it alleviates neuropathic allodynia after 3 days of treatment.
      Naloxone had no effect on gabapentin therapeutic benefit, showing that
      antidepressants and anticonvulsants alleviate neuropathic allodynia through
      independent mechanisms. Our work provides a clinically relevant model to
      understand the mechanism by which chronic antidepressant treatment can alleviate
      neuropathic pain.

PMID- 18331805
TI  - Interaction between anxiety, depression, quality of life and clinical parameters
      in chronic tension-type headache.
AB  - Our aim was to investigate the mediating or moderating role of anxiety and
      depression in the relationship between headache clinical parameters and quality
      of life in Chronic Tension-Type Headache (CTTH). Twenty-five patients diagnosed
      with CTTH according to the criteria of the International Headache Society were
      studied. A headache diary was kept for 4 weeks in order to substantiate the
      diagnosis and record the pain history. Quality of life was assessed by means of
      the Medical Outcome Study (MOS) 36-Item Short-Form (SF-36) questionnaire. The
      Beck Depression Inventory (BDI-II) was used to assess depression, and the Trait
      Anxiety Scale (TA) from the State-Trait Anxiety Inventory was administered in
      order to assess anxiety. Moderating and mediating analyses were conducted with
      ordinary least squares multiple regression analysis using the SPSS General Linear
      Model procedure. Anxiety mediated the effect between headache frequency and
      quality of life, but not the effect of either headache intensity or duration.
      Anxiety totally mediated the effects of headache frequency on vitality, social
      functioning and mental health. On the other hand, depression modulated the effect
      in the mental health domain. The effect in the mental health domain was a
      function of the interaction between headache duration and depression (beta=-0.34,
      p<0.05), after controlling for age, gender, the main effects of headache
      duration, and depression. We did not find anxiety to be a moderating factor
      between intensity, frequency or duration of headache and perceived quality of
      life. Anxiety exerts a mediating effect, conditioning the relationship between
      headache frequency and some quality of life domains; depression seems to play an
      inherent role in the reduced quality of life of these patients, that is, it has a
      moderating effect.

PMID- 18331806
TI  - Differential gene expression induced by growth hormone treatment in the uremic
      rat growth plate.
AB  - OBJECTIVES: Treatment with growth hormone (GH) improves growth retardation of
      chronic renal failure. cDNA microarrays were used to investigate GH-induced
      modifications in gene expression in the tibial growth plate of young rats.
      DESIGN: RNA was extracted from the tibial growth plate from two groups, untreated
      and treated with GH, of young rats made uremic by subtotal nephrectomy (n=10). To
      validate changes shown by the Agilent oligo microarrays, some modulated genes
      known to play a physiological role in growth plate metabolism were analyzed by
      real-time quantitative polymerase chain reaction (qPCR). RESULTS: The microarrays
      showed that GH modified the expression of 224 genes, 195 being upregulated and 29
      downregulated. qPCR results confirmed the sense of expression change found in the
      arrays for insulin-like growth factor I, insulin-like growth factor II, collagen
      V alpha 1, bone morphogenetic protein 3 and proteoglycan type II. CONCLUSIONS:
      This study shows for the first time the profile of growth plate gene expression
      modifications caused by GH treatment in experimental uremia and provides a basis
      to further investigate selected individual genes with potential implication in
      the stimulating effect on the growth of GH treatment in chronic renal failure.

PMID- 18331807
TI  - Transaldolase deficiency in a two-year-old boy with cirrhosis.
AB  - Transaldolase (TALDO) deficiency is a rare inborn error of the pentose phosphate
      pathway. We report the clinical presentation and laboratory findings of a new
      patient with TALDO deficiency. The two-year-old Arabic boy presented with
      neonatal onset of anemia and thrombocytopenia, tubulopathy, and rickets and was
      subsequently found to have cirrhosis and deafness. A comparison with other TALDO
      deficient patients is given.

PMID- 18331808
TI  - Technical approaches to the optimisation of CT.
AB  - This paper reviews current technical approaches to the optimisation of CT
      practice, i.e. approaches to reduce patient dose to the necessary minimum. The
      most important step towards this goal appears to be the technology of tube
      current modulation (TCM), which came into practice in the early 2000s and has
      become the standard approach recently. Anatomy- or attenuation-based TCM allows
      for a dose reduction between 10 and 60% as compared to scans with constant tube
      current. Automatic exposure control (AEC) approaches are the next step; based on
      TCM technology, AEC adapts the tube current both with the rotation angle alpha
      (alpha-modulation) and along the z-axis (z-modulation) to achieve a pre-selected
      image quality level at minimal dose. To pre-select the image quality level, i.e.
      primarily the pixel noise level, tools for simulation are important to
      investigate the necessary noise levels pro- and retrospectively for given cases
      and diagnostic tasks. Respective "dose tutor" approaches have become available
      recently and are presented. The most recent technical innovation which may lead
      to substantial dose reduction is the investigation of optimal spectra taking the
      type of contrast and 3D dose distributions into account. A high potential has
      been shown especially for pediatric CT and for thoracic CT where dose reduction
      of a factor of 2 and more is possible when using reduced tube voltages.

PMID- 18331809
TI  - Dynamic heart phantom for the quality control of SPECT equipment.
AB  - A nuclear imaging of heart is a noninvasive procedure that reveals the cardiac
      structure and physiology enabling evaluation of cardiac function. According to
      the regulations published by the Polish Government and the Polish Ministry of
      Health, the nuclear medicine departments must follow the new legislation which
      has imposed quality assurance (QA) and quality control (QC) of equipment and
      medical testing procedures as compulsory. The foremost reason to perform QC tests
      of medical imaging equipment, using ionizing radiation, is to assure the
      provision of the best possible diagnostic service to the patient with the least
      radiological hazard. One of the most common ways of testing in nuclear medicine
      is using phantoms. The aim of this study was to design and perform a dynamic
      heart phantom. The heart phantom was designed according to directive of the ICRU
      Report 48. It consists of a pump, tubes, cardiac volume and a membrane simulating
      left ventricle. The pump compresses and decompresses membrane. The pumping
      frequency can be changed from 60 to 200 bpm. The phantom cardiac volume should be
      filled with radiopharmaceutical. The elaborated dynamic heart phantom is used for
      QC of imaging system in nuclear medicine department. The QC measurements were
      performed with the phantom filled with 45-50 MBq of (99m)Tc-MIBI solution and
      placed in water filled anthropomorphic torso phantom. The dynamic heart phantom
      can also be used to simulate all types of the myocardial infarctions and help to
      choose the best geometry of the measurement.

PMID- 18331810
TI  - Studies in use of the Greulich-Pyle skeletal age method to assess criminal
      liability.
AB  - In recent years, skeletal age determination has become increasingly important for
      determining the age of live subjects as part of criminal investigation. The most
      widely used method worldwide to determine skeletal age is the Greulich-Pyle atlas
      method. The present study examines the suitability of the Greulich-Pyle method
      given the particular requirements of forensic age estimates. It is a
      retrospective analysis of 649 hand radiographs originally taken from persons aged
      between 1 and 18 years, separately for each sex. If the Greulich-Pyle method is
      used exclusively, it can be claimed with a probability of 95% that a young man
      has reached the age of 14 years and thus the age of criminal liability if his
      skeletal age is at least 15.5 years. In the case of female subjects, even if they
      are estimated as being 16.0 years old, it cannot be asserted with a probability
      of 95% that they have reached the age of 14. To reduce the margin of error of age
      estimates, determining the skeletal age should always go hand in hand with a
      physical examination to determine indications of sexual maturity and a dental
      examination to record dental status. The reference values given in the present
      study can be applied to members of all ethnic groups for age estimate purposes.
      If the person under examination has a different socio-economic status, the expert
      performing the age estimate should address this issue in his expert opinion and
      discuss the possible effects that might have on the age diagnosis.

PMID- 18331811
TI  - Brain perfusion abnormalities in a sibship with parkin-linked parkinsonism.
AB  - We demonstrated brain perfusion abnormalities in a sibship with parkin-linked
      parkinsonism. The sibship consisted of a 64-year-old man and a 62-year-old woman.
      Both patients had homozygous deletions of exon 4 in the parkin gene.
      Hypoperfusion in the superior and middle frontal gyrus, and head of caudate
      nucleus was seen by SPECT with easy Z score imaging system in both patients.
      These findings may reflect their executive dysfunction demonstrated by
      neuropsychological tests.

PMID- 18331812
TI  - EEG power and coherence in autistic spectrum disorder.
AB  - OBJECTIVE: Autistic spectrum disorder (ASD) has been defined as a
      neurodevelopmental disorder with associated deficits in executive function,
      language, emotional, and social function. ASD has been associated with
      pathophysiology in cerebral organization. The current study investigated
      quantitative EEG findings in twenty children diagnosed with autistic disorders as
      compared to 20 controls matched for gender, age and IQ. METHODS: The EEG was
      recorded during an eyes-closed resting condition and topographical differences in
      cerebral functioning were examined using estimates of absolute, relative, and
      total power, as well as intrahemispheric and interhemispheric coherences.
      RESULTS: There were group differences in power, intrahemispheric and
      interhemispheric coherences. Findings included excessive theta, primarily in
      right posterior regions, in autistics. There was also a pattern of deficient
      delta over the frontal cortex and excessive midline beta. More significantly,
      there was a pattern of underconnectivity in autistics compared to controls. This
      included decreased intrahemispheric delta and theta coherences across short to
      medium and long inter-electrode distances. Interhemispherically, delta and theta
      coherences were low across the frontal region. Delta, theta and alpha
      hypocoherence was also evident over the temporal regions. Lastly, there were low
      delta, theta and beta coherence measurements across posterior regions.
      CONCLUSIONS: These results suggest dysfunctional integration of frontal and
      posterior brain regions in autistics along with a pattern of neural
      underconnectivity. This is consistent with other EEG, MRI and fMRI research
      suggesting that neural connectivity anomalies are a major deficit leading to
      autistic symptomatology. SIGNIFICANCE: This paper reports the largest integrated
      study of EEG power and coherence during a resting state in children suffering
      autism spectrum disorder.

PMID- 18331813
TI  - Re-donation intentions among experienced blood donors: does gender make a
      difference?
AB  - Path analysis was used to examine sex differences in motivation for repeat
      donation among experienced blood donors. Results confirm the importance of
      constructs from the Theory of Planned Behavior (e.g., donation attitude,
      subjective norm, personal moral norm, and donation self-efficacy) and of prior
      donation experience (e.g., vasovagal symptoms, overall satisfaction) as
      significant predictors of donation intention. Importantly, the findings also
      indicate that a consideration of sex differences in donor motivations results in
      a better prediction model and suggests a framework of possible avenues where
      interventions could be expected to improve donor return rates.

PMID- 18331814
TI  - Therapeutic plasma exchange in patients with neurologic diseases: retrospective
      multicenter study.
AB  - Therapeutic plasma exchange (TPE) is commonly used in many neurological disorders
      where an immune etiology was known or suspected. We report our experience with
      TPE performed for neuroimmunologic disorders at four university hospitals. The
      study was a retrospective review of the medical records of neurological patients
      (n=57) consecutively treated with TPE between April 2006 and May 2007. TPE
      indications in neurological diseases included Guillain-Barre Syndrome (GBS)
      (n=41), myasthenia gravis (MG) (n=11), acute disseminated encephalomyelitis
      (ADEM) (n=3), chronic inflammatory demyelinating polyneuropathy (CIDP) (n=1) and
      multiple sclerosis (MS) (n=1). Patient median age was 49; there was a
      predominance of males. Twenty-two patients had a history of other therapy
      including intravenous immunoglobulin (IVIG), steroid, azothioprin, and
      pridostigmine prior to TPE. Another 35 patients had not received any treatment
      prior to TPE. All patients were classified according to the Hughes functional
      grading scores pre- and first day post-TPE for early clinical evaluation of
      patients. The TPE was carried out 1-1.5 times at the predicted plasma volume
      every other day. Two hundred and ninety-four procedures were performed on 57
      patients. The median number of TPE sessions per patient was five, and the median
      processed plasma volume was 3075mL for each cycle. Although the pre-TPE median
      Hughes score of all patients was 4, it had decreased to grade 1 after TPE. While
      the pre-TPE median Hughes score for GBS and MG patients was 4, post-TPE scores
      were decreased to grade 1. Additionally, there was a statistically significant
      difference between post-TPE Hughes score for GBS patients with TPE as front line
      therapy and patients receiving IVIG as front line therapy (1 vs. 3.5; p=0.034).
      Although there was no post-TPE improvement in Hughes scores in patients with ADEM
      and CIDP, patients with MS had an improved Hughes score from 4 to 1. Mild and
      manageable complications such as hypotension and hypocalcemia were also observed.
      TPE may be preferable for controlling symptoms of neuroimmunological disorders in
      early stage of the disease, especially with GBS.

PMID- 18331815
TI  - Automatic detection of immature platelets for decision making regarding platelet
      transfusion indications for pediatric patients.
AB  - Immature or reticulated platelets are known as a clinical marker of
      thrombopoiesis. Recently, an automatic method was established to detect
      reticulated platelets as immature platelet fraction (IPF) by means of hematology
      analyzer XE-2100. We assessed the effects of IPF detection after chemotherapy for
      various pediatric malignant disorders of 16 patients. Our results indicate that
      IPF should be considered a useful marker of imminent platelet recovery so that
      unnecessary platelet transfusion can be avoided.

PMID- 18331816
TI  - Efficacy, tolerability, and side effects of oxcarbazepine monotherapy: a
      prospective study in adult and elderly patients with newly diagnosed partial
      epilepsy.
AB  - OBJECTIVE: The aim of the study described here was to investigate the efficacy,
      tolerability, and side effects of oxcarbazepine (OXC) monotherapy in newly
      diagnosed, previously untreated adult and elderly patients with partial epilepsy.
      METHODS: We prospectively analyzed and recorded the efficacy, tolerability, and
      side effects of OXC monotherapy. The results were analyzed on the basis of
      etiologic classifications and age distributions. Remission was defined as seizure
      freedom for at least 1 year. RESULTS: A total of 147 patients were evaluated in a
      single center for a median of 18 months (range: 14-36 months). Overall, 92
      patients (62.6%) were seizure free for at least 12 months and 55 of them (37.4%)
      were unresponsive despite treatment with the maximum tolerable dose of OXC. There
      was a significant difference in the outcomes of patients with cryptogenic (75%
      remission) and symptomatic (51.9% remission) epilepsy (P=0.004). Patients with
      cerebral tumors did worse than the remainder of the patients in the symptomatic
      group (36.7% remission) (P=0.03). Results were favorable for the elderly; 14
      patients (73.6%) in the elderly subgroup became seizure free for at least 1 year,
      and the remission was achieved with low to moderate doses (approximately 900
      mg/day). Overall, 13 patients (8.8%) discontinued OXC due to intolerable side
      effects. Side effects leading to discontinuation were: Stevens-Johnson syndrome
      (n=2, 1.4%); fatigue and drowsiness (n=2, 1.4%); dizziness, nausea, and vomiting
      with normal laboratory tests (n=2, 1.4%); dizziness, nausea, and vomiting with
      serum Na levels <130 mEq/L (n=5, 3.4%); and elevated serum gamma-glutamyl
      transferase levels (GGT>200mg/dL) (n=1, 0.7%). OXC proved to be a tolerable drug
      for the elderly; only one patient experienced symptomatic hyponatremia with mild
      symptoms and responded well to fluid restriction, which did not lead to
      discontinuation of OXC. CONCLUSION: Although the limitations of our study include
      its open-label design, the results suggest that OXC monotherapy may be regarded
      as an effective first-line monotherapy option for adult and elderly patients with
      partial epilepsy, but has low efficacy in patients with cerebral tumors.

PMID- 18331817
TI  - Dynamic mechanical behavior of starch-based scaffolds in dry and physiologically
      simulated conditions: effect of porosity and pore size.
AB  - The three-dimensional scaffolds of a blend of starch and poly(L-lactic) acid,
      SPLA70, were produced using compression molding of polymer/salt mixture followed
      by leaching of salt. One series of scaffolds were prepared with varying polymer
      to-salt ratio while keeping the salt size constant, and the other series of
      scaffolds were prepared with varying salt sizes while keeping the polymer-to-salt
      ratio constant. The X-ray microcomputed tomography and scanning electron
      microscopy assay were used to analyze the porous morphologies, porosity and
      distribution of porosity of the porous scaffolds. Salt-free and integrated SPLA70
      scaffolds with porosities ranging from 74% to 82% and pore sizes of 125-250 to
      500-1000 microm can be fabricated using the present fabrication technique. The
      water uptake of the SPLA70 scaffolds increases with increasing porosities and
      also with increasing pore size. In dry state, the storage modulus decreases with
      increasing porosity and also with increasing pore size. The normalized modulus
      values are related to normalized density of the scaffolds by a power-law function
      with an exponent between 2 and 3. For the immersed scaffolds under physiological
      conditions, the storage modulus was less dependent on porosity and pore size.
      However, the loss factor increased significantly compared with dry state
      measurements. The present study clearly shows that the mechanical performance of
      porous polymeric constructs in dry and in immersed state is completely different,
      and for comparison with biomechanical performance of tissues, the tests should
      ideally be performed in immersed state.

PMID- 18331818
TI  - Transcription factors controlling osteoblastogenesis.
AB  - The recent development of molecular biology and mouse genetics and the analysis
      of the skeletal phenotype induced by genetic mutations in humans led to a better
      understanding of the role of transcription factors that govern bone formation.
      This review summarizes the role of transcription factors in osteoblastogenesis
      and provides an integrated perspective on how the activities of multiple classes
      of factors are coordinated for the complex process of developing the osteoblast
      phenotype. The roles of Runx2, the principal transcriptional regulator of
      osteoblast differentiation, Osterix, beta-Catenin and ATF which act downstream of
      Runx2, and other transcription factors that contribute to the control of
      osteoblastogenesis including the AP1, C/EBPs, PPARgamma and homeodomain, helix
      loop-helix proteins are discussed. This review also updates the regulation of
      transcription factor expression by signaling factors and hormones that control
      osteoblastogenesis.

PMID- 18331819
TI  - Redox and heavy metal effects on the biochemical activities of an Arabidopsis
      polyadenylation factor subunit.
AB  - The Arabidopsis CPSF30 ortholog (AtCPSF30) is an RNA-binding endonuclease that is
      part of the plant polyadenylation complex. Previous work (B. Addepalli, A.G.
      Hunt, Nucleic Acids Res. 35 (2007) 4453-4463) demonstrated that different zinc
      finger motifs in the protein were responsible for RNA-binding and nuclease
      activity, respectively. In this study, a more detailed functional map of AtCPSF30
      is presented, a map that includes descriptions of novel biochemical activities.
      Elevated temperatures, the specific zinc chelator 1,10-phenanthroline, and the
      sulfhydryl reagent dithiothreitol all had differential inhibitory effects on the
      RNA-binding and nuclease activities. The endonuclease activity of AtCPSF30 was
      inhibited by relatively high (>100muM) concentrations of zinc, and this
      inhibition required a plant-specific N-terminal domain apart from the zinc finger
      core of the protein. ATP stimulated the nuclease activity in the presence of
      zinc, and this stimulation required a plant-specific C-terminal domain, again
      apart from the zinc finger core. These studies reveal a subtle and unexpected
      complexity to AtCPSF30, and raise the possibility that multiple avenues of
      regulation may impinge on this protein through different functional domains.

PMID- 18331820
TI  - Phosphorylation-dependent regulation of excitation energy distribution between
      the two photosystems in higher plants.
AB  - Phosphorylation-dependent movement of the light-harvesting complex II (LHCII)
      between photosystem II (PSII) and photosystem I (PSI) takes place in order to
      balance the function of the two photosystems. Traditionally, the phosphorylatable
      fraction of LHCII has been considered as the functional unit of this dynamic
      regulation. Here, a mechanical fractionation of the thylakoid membrane of
      Spinacia oleracea was performed from leaves both in the phosphorylated state (low
      light, LL) and in the dephosphorylated state (dark, D) in order to compare the
      phosphorylation-dependent protein movements with the excitation changes occurring
      in the two photosystems upon LHCII phosphorylation. Despite the fact that several
      LHCII proteins migrate to stroma lamellae when LHCII is phosphorylated, no
      increase occurs in the 77 K fluorescence emitted from PSI in this membrane
      fraction. On the contrary, such an increase in fluorescence occurs in the grana
      margin fraction, and the functionally important mobile unit is the PSI-LHCI
      complex. A new model for LHCII phosphorylation driven regulation of relative
      PSII/PSI excitation thus emphasises an increase in PSI absorption cross-section
      occurring in grana margins upon LHCII phosphorylation and resulting from the
      movement of PSI-LHCI complexes from stroma lamellae and subsequent co-operation
      with the P-LHCII antenna from the grana. The grana margins probably give a
      flexibility for regulation of linear and cyclic electron flow in plant
      chloroplasts.

PMID- 18331821
TI  - Membrane processes and biophysical characterization of living cells decorated
      with chromatic polydiacetylene vesicles.
AB  - The structural complexity of the cell membrane makes analysis of membrane
      processes in living cells, as compared to model membrane systems, highly
      challenging. Living cells decorated with surface-attached
      colorimetric/fluorescent polydiacetylene patches might constitute an effective
      platform for analysis and visualization of membrane processes in situ. This work
      examines the biological and chemical consequences of plasma membrane labeling of
      promyelocytic leukemia cells with polydiacetylene. We show that the extent of
      fusion between incubated lipid/diacetylene vesicles and the plasma membrane is
      closely dependent upon the lipid composition of both vesicles and cell membrane.
      In particular, we find that cholesterol presence increased bilayer fusion between
      the chromatic vesicles and the plasma membrane, suggesting that membrane
      organization plays a significant role in the fusion process. Spectroscopic data
      and physiological assays show that decorating the cell membrane with the
      lipid/diacetylene patches reduces the overall lateral diffusion within the
      membrane bilayer, however polydiacetylene labeling does not adversely affect
      important cellular metabolic pathways. Overall, the experimental data indicate
      that the viability and physiological integrity of the surface-engineered cells
      are retained, making possible utilization of the platform for studying membrane
      processes in living cells. We demonstrate the use of the polydiacetylene-labeled
      cells for visualizing and discriminating among different membrane interaction
      mechanisms of pharmaceutical compounds.

PMID- 18331822
TI  - Identification of Tom5 and Tom6 in the preprotein translocase complex of human
      mitochondrial outer membrane.
AB  - The fungal preprotein translocase of the mitochondrial outer membrane (TOM
      complex) comprises import receptors Tom70, Tom20, and Tom22, import channel
      Tom40, and small Tom proteins Tom5, Tom6, and Tom7, which regulate TOM complex
      assembly. These components are conserved in mammals; unlike the other components,
      however, Tom5 and Tom6 remain unidentified in mammals. We immuno-isolated the TOM
      complex from HeLa cells expressing hTom22-FLAG and identified the human
      counterparts of Tom5 and Tom6, together with the other components including Tom7.
      These small Tom proteins are associated with Tom40 in the TOM complex. Knockdown
      of Tom7, but not Tom5 and Tom6, strongly compromised stability of the TOM
      complex. Conversely, knockdown of hTom40 decreased the level of all small Tom
      proteins. Matrix import of preprotein was affected by double knockdown of any
      combination of small Tom proteins. These results indicate that human small Tom
      proteins maintain the structural integrity of the TOM complex.

PMID- 18331823
TI  - Variant histone H2A.Z, but not the HMG proteins Nhp6a/b, is essential for the
      recruitment of Swi/Snf, Mediator, and SAGA to the yeast GAL1 UAS(G).
AB  - Chromatin architecture is very important for the regulation of transcriptional
      activation. Here, we investigated the role of two different chromatin components,
      the histone variant H2A.Z and HMG proteins Nhp6a/b, in regulating GAL1 gene
      expression. We have shown that recruitment of the Mediator complex is
      significantly affected in the absence of H2A.Z. Furthermore, H2A.Z is also
      required to fully recruit the SAGA and Swi/Snf complexes to the yeast GAL1-10
      UAS(G). On the other hand, the HMG protein Nhp6a/b is not required to recruit the
      aforementioned components to the GAL1 promoter. The Nhp6 protein has been shown
      to interact with nucleosomes, and we show that its distribution is unaffected in
      the absence of H2A.Z. Our results suggest that the incorporation of the histone
      variant H2A.Z, but not the HMG proteins Nhp6a/b, in promoter regions creates a
      specialized chromatin domain that is required for pre-initiation complex assembly
      at the GAL1 locus.

PMID- 18331824
TI  - Short interfering RNA directed against TWIST, a novel zinc finger transcription
      factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial
      pathway.
AB  - Previous reports have implicated epithelial-mesenchymal transition (EMT) as a
      major cause of cancer. TWIST, a novel zinc finger transcription factor, was
      suggested to be an important inducer of EMT and therefore be involved in
      different phases of tumorigenicity. However, whether TWIST suppression could
      increase chemosensitivity of cancer cells to chemotherapeutic agent remains
      unclear. In the present study, we utilized RNA interference to knockdown TWIST
      expression in A549 cells and further assessed the cell viability and apoptosis as
      well as possible MAPKs and mitochondrial pathways. The data showed that TWIST
      depletion significantly sensitized A549 cells to cisplatin by inducing activation
      of JNK/mitochondrial pathway but not ERK and p-38 pathways, suggesting critical
      roles of TWIST in A549 cell chemoresistance to cisplatin and raising the
      possibility of TWIST depletion as a promising approach to lung cancer therapy.

PMID- 18331825
TI  - Common marmoset embryonic stem cell can differentiate into cardiomyocytes.
AB  - Common marmoset monkeys have recently attracted much attention as a primate
      research model, and are preferred to rhesus and cynomolgus monkeys due to their
      small bodies, easy handling and efficient breeding. We recently reported the
      establishment of common marmoset embryonic stem cell (CMESC) lines that could
      differentiate into three germ layers. Here, we report that our CMESC can also
      differentiate into cardiomyocytes and investigated their characteristics. After
      induction, FOG-2 was expressed, followed by GATA4 and Tbx20, then Nkx2.5 and
      Tbx5. Spontaneous beating could be detected at days 12-15. Immunofluorescent
      staining and ultrastructural analyses revealed that they possessed
      characteristics typical of functional cardiomyocytes. They showed sinus node-like
      action potentials, and the beating rate was augmented by isoproterenol
      stimulation. The BrdU incorporation assay revealed that CMESC-derived
      cardiomyocytes retained a high proliferative potential for up to 24 weeks. We
      believe that CMESC-derived cardiomyocytes will advance preclinical studies in
      cardiovascular regenerative medicine.

PMID- 18331826
TI  - Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell
      proliferation.
AB  - Constitutive androstane receptor (CAR) is a transcription factor to regulate the
      expression of several genes related to drug-metabolism. Here, we demonstrate that
      CAR protein accumulates during G1 in human SW480 and HepG2 cells. After the G1/S
      phase transition, CAR protein levels decreased, and CAR was hardly detected in
      cells by the late M phase. CAR expression in both cell lines was suppressed by
      RNA interference-mediated suppression of CDK4. Depletion of CAR by RNA
      interference in both cells and by hepatocyte growth factor treatment in HepG2
      cells resulted in decreased MDM2 expression that led to p21 upregulation and
      repression of HepG2 cell growth. Thus, our results demonstrate that CAR
      expression is an early G1 event regulated by CDK4 that contributes to MDM2
      expression; these findings suggest that CAR may influence the expression of genes
      involved in not only the metabolism of endogenous and exogenous substances but
      also in the cell proliferation.

PMID- 18331827
TI  - The novel gene AngRem104 downregulates glucocorticoid receptor expression and
      activates NF-kappaB in human mesangial cells.
AB  - AngRem104 [angiotensin II (Ang II)-related genes in human mesangial cells (MCs),
      clone104], a novel gene in human MCs induced by Ang II, was previously identified
      in human MCs and found to interact with several proteins. The current study used
      a yeast two-hybrid system and co-immunoprecipitation to investigate the
      interaction between AngRem104 and glucocorticoid receptor (GR) AF-1-specific
      elongation factor (GR-EF). GR expression was downregulated and the number of MCs
      positive for activated nuclear factor kappaB (NF-kappaB) was increased when
      AngRem104 was overexpressed. Transfection with antisense AngRem104 vector
      resulted in the upregulation of GR protein and reduced numbers of MCs with
      activated NF-kappaB. These results indicate that the novel gene AngRem104 is
      involved in the in vivo regulation of GR expression and the activation of NF
      kappaB through interaction with GR-EF in human MCs.

PMID- 18331828
TI  - Skeletal muscle Kv7 (KCNQ) channels in myoblast differentiation and
      proliferation.
AB  - Voltage-dependent K(+) channels (Kv) are involved in myocyte proliferation and
      differentiation by triggering changes in membrane potential and regulating cell
      volume. Since Kv7 channels may participate in these events, the purpose of this
      study was to investigate whether skeletal muscle Kv7.1 and Kv7.5 were involved
      during proliferation and myogenesis. Here we report that, while myotube formation
      did not regulate Kv7 channels, Kv7.5 was up-regulated during cell cycle
      progression. Although, Kv7.1 mRNA also increased during the G(1)-phase,
      pharmacological evidence mainly involves Kv7.5 in myoblast growth. Our results
      indicate that the cell cycle-dependent expression of Kv7.5 is involved in
      skeletal muscle cell proliferation.

PMID- 18331829
TI  - Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from
      Chk1.
AB  - Chk1 protein kinase plays a critical role in checkpoints that restrict
      progression through the cell cycle if DNA replication has not been completed or
      DNA damage has been sustained. ATR-dependent activation of Chk1 is mediated by
      Claspin. Phosphorylation of Claspin at two sites (Thr916 and Ser945 in humans) in
      response to DNA replication arrest or DNA damage recruits Chk1 to Claspin. Chk1
      is subsequently phosphorylated by ATR and fully activated to control cell cycle
      progression. We show that ablation of Chk1 by siRNA in human cells or its genetic
      deletion in chicken DT40 cells does not prevent phosphorylation of Claspin at
      Thr916 (Ser911 in chicken). Chk1, however, does play other roles, possibly
      indirect, in the phosphorylation of Claspin and its induction. These results
      demonstrate that phosphorylation of Claspin within the Chk1-binding domain is
      catalysed by an ATR-dependent kinase distinct from Chk1.

PMID- 18331830
TI  - Fast skeletal muscle troponin I is a co-activator of estrogen receptor-related
      receptor alpha.
AB  - ERRalpha (estrogen receptor-related receptor alpha) is a member of the nuclear
      receptor superfamily. To further our understanding of the detailed molecular
      mechanism of transcriptional regulation by ERRalpha, we searched for ERRalpha
      interacting proteins using a yeast two-hybrid system by screening a human mammary
      gland cDNA expression library with the ligand-binding domain (LBD) of ERRalpha as
      the "bait". Fast skeletal muscle troponin I (TNNI2), along with several known
      nuclear receptor co-activators, were isolated. We demonstrated that TNNI2
      localizes to the cell nucleus and interacts with ERRalpha in co
      immunoprecipitation experiments. GST pull-down assays also revealed that TNNI2
      interacts directly with ERRalpha. Through luciferase reporter gene assays, TNNI2
      was found to enhance the transactivity of ERRalpha. Combining mutagenesis and
      yeast two-hybrid assays, we mapped the ERRalpha-interacting domain on TNNI2 to a
      region encompassing amino acids 1-128. These findings reveal a new function for
      TNNI2 as a co-activator of ERRalpha.

PMID- 18331831
TI  - Investigating complexity of protein-protein interactions in focal adhesions.
AB  - The formation of focal adhesions governs cell shape and function; however, there
      are few measurements of the binding kinetics of focal adhesion proteins in living
      cells. Here, we used the fluorescence recovery after photobleaching (FRAP)
      technique, combined with mathematical modeling and scaling analysis to quantify
      dissociation kinetics of focal adhesion proteins in capillary endothelial cells.
      Novel experimental protocols based on mathematical analysis were developed to
      discern the rate-limiting step during FRAP. Values for the dissociation rate
      constant k(OFF) ranged over an order of magnitude from 0.009+/-0.001/s for talin
      to 0.102+/-0.010/s for FAK, indicating that talin is bound more strongly than
      other proteins in focal adhesions. Comparisons with in vitro measurements reveal
      that multiple focal adhesion proteins form a network of bonds, rather than
      binding in a pair-wise manner in these anchoring structures in living cells.

PMID- 18331832
TI  - Effects on capacitance by overexpression of membrane proteins.
AB  - Functional Channelrhodopsin-2 (ChR2) overexpression of about 10(4)channels/mum(2)
      in the plasma membrane of HEK293 cells was studied by patch-clamp and freeze
      fracture electron microscopy. Simultaneous electrorotation measurements revealed
      that ChR2 expression was accompanied by a marked increase of the area-specific
      membrane capacitance (C(m)). The C(m) increase apparently resulted partly from an
      enlargement of the size and/or number of microvilli. This is suggested by a
      relatively large C(m) of 1.15+/-0.08 microF/cm(2) in ChR2-expressing cells
      measured under isotonic conditions. This value was much higher than that of the
      control HEK293 cells (0.79+/-0.02 microF/cm(2)). However, even after complete
      loss of microvilli under strong hypoosmolar conditions (100 mOsm), the ChR2
      expressing cells still exhibited a significantly larger C(m) (0.85+/-0.07
      microF/cm(2)) as compared to non-expressing control cells (0.70+/-0.03
      microF/cm(2)). Therefore, a second mechanism of capacitance increase may involve
      changes in the membrane permittivity and/or thickness due to the embedded ChR2
      proteins.

PMID- 18331833
TI  - Ionizing radiation downregulates ASPM, a gene responsible for microcephaly in
      humans.
AB  - Microcephaly is a malformation associated with in utero exposed atomic bomb
      survivors and can be induced in mice by fetal exposure to ionizing radiation
      (IR). The pathogenesis of IR-induced microcephaly, however, has not been fully
      understood. Our analyses of high-coverage expression profiling (HiCEP)
      demonstrated that the abnormal spindle-like microcephaly associated gene (ASPM)
      was down-regulated in irradiated human diploid fibroblasts. ASPM was recently
      reported as the causative gene for MCPH-5, the most common type of congenital
      microcephaly in humans. Here, we show that the expression of the Aspm gene was
      significantly reduced by IR in various human and murine cells. Additionally, Aspm
      was found downregulated in the irradiated fetal mouse brain, particularly in the
      ventricular zones. A similar suppression was observed in the irradiated
      neurosphere cultures. This is the first report suggesting that the suppression of
      Aspm by IR could be the initial molecular target leading to the future
      microcephaly formation.

PMID- 18331834
TI  - TRPV1 mediates cell death in rat synovial fibroblasts through calcium entry
      dependent ROS production and mitochondrial depolarization.
AB  - Synoviocyte hyperplasia is critical for rheumatoid arthritis, therefore,
      potentially an important target for therapeutics. It was found in this work that
      a TRPV1 agonist capsaicin, and acidic solution (pH 5.5) induced increases in
      cytosolic calcium concentration ([Ca(2+)](c)) and reactive oxygen species (ROS)
      production in synoviocytes isolated from a rat model of collagen-induced
      arthritis. The increases in both [Ca(2+)](c) and ROS production were completely
      abolished in calcium-free buffer or by a TRPV1 antagonist capsazepine. Further
      experiments revealed that capsaicin and pH 5.5 solution caused mitochondrial
      membrane depolarization and reduction in cell viability; such effects were
      inhibited by capsazepine, or the NAD(P)H oxidase inhibitor diphenylene iodonium.
      Both capsaicin and pH 5.5 buffer induced apoptosis as shown by nuclear
      condensation and fragmentation. Furthermore, RT-PCR readily detected TRPV1 mRNA
      expression in the isolated synoviocytes. Taken together, these data indicated
      that TRPV1 activation triggered synoviocyte death by [Ca(2+)](c) elevation, ROS
      production, and mitochondrial membrane depolarization.

PMID- 18331835
TI  - The PHY domain is required for conformational stability and spectral integrity of
      the bacteriophytochrome from Deinococcus radiodurans.
AB  - Bacteriophytochrome from Deinococcus radiodurans (DrBphP) is a plant phytochrome
      homolog. To investigate the interaction of chromophore and protein structure, we
      purified recombinant DrBphP and performed biochemical analyses. Differences of
      apo- and holo-protein in electrophoretic properties in native gels and their
      susceptibility to trypsin indicate changes in both the conformation and surface
      topography of this protein as a result of chromophore assembly. Furthermore,
      proteolysis to Pr and Pfr conformers displayed distinctive cleavage patterns with
      a noticeable Pr-specific tryptic fragment. Of interest, a prolonged tryptic
      digestion showed a more severe impact upon the Pfr form. Most importantly, when
      we assessed the extent of dark reversion to evaluate the role of the cleaved
      part, a rapidly accelerated reversion was observed upon cleavage at residues 329
      505 corresponding to the PHY domain. Our data thus show that the PHY domain is
      necessary for the Pfr stabilization and spectral integrity of DrBphP.

PMID- 18331836
TI  - RN181, a novel ubiquitin E3 ligase that interacts with the KVGFFKR motif of
      platelet integrin alpha(IIb)beta3.
AB  - We previously identified proteins that bind with high affinity to a peptide
      corresponding to the cytoplasmic regulatory domain (KVGFFKR) of the platelet
      specific integrin subunit alpha(IIb). These included a hypothetical protein
      termed HSPC238, recently renamed as RING finger protein, RN181. Here, we
      establish the presence of RN181 in human platelets by RT-PCR, Western blotting
      and mass spectrometry and confirm its affinity for the platelet integrin. We
      demonstrate that RN181 has ubiquitin E3 ligase activity and that all other
      components of the ubiquitination pathway are abundant in platelets, suggesting a
      novel link of integrin signal transduction pathways with ubiquitin-conjugation
      events.

PMID- 18331837
TI  - Molecular investigations of a novel iduronate-2-sulfatase mutant in a Chinese
      patient.
AB  - BACKGROUND: Molecular investigations of iduronate-2-sulfatase (IDS) mutants for
      the X-linked lysosomal storage disease mucopolysaccharidosis type II (MPS II,
      Hunter disease), commonly depends on transient expression studies to verify a
      single nucleotide change to be pathogenic. In 2 severely affected patients, IDS
      missense mutations, c.1016T>C (novel) and c.1016T>G (known) were identified
      predicting the substitution of an ambivalent cyclic proline and a hydrophilic
      arginine respectively for the hydrophobic leucine at residue 339. We hypothesized
      that residue Leu339 may be functionally critical. METHODS: We performed a study
      for the 2 mutations by in-situ mutagenesis, in vitro expression, and functional
      analysis. RESULTS: Transient expression revealed that both the missense variants
      had stable mRNA but their residual enzyme activities remained <2.5% of normal
      level. The effect of the missense mutations on protein expression was detected by
      Western blot analysis. Both the missense mutations synthesized the precursor form
      but had reduced mature form of IDS. CONCLUSION: The novel mutation p.L339P is a
      disease-causing mutation affecting maturation of the protein.

PMID- 18331838
TI  - TTLL10 is a protein polyglycylase that can modify nucleosome assembly protein 1.
AB  - Certain proteins can undergo polyglycylation and polyglutamylation.
      Polyglutamylases (glutamate ligases) have recently been identified in a family of
      tubulin tyrosine ligase-like (TTLL) proteins. However, no polyglycylase (glycine
      ligase) has yet been reported. Here we identify a polyglycylase in the TTLL
      proteins by using an anti-poly-glycine antibody. The antibody reacted with a
      cytoplasmic 60-kDa protein that accumulated in elongating spermatids. Using
      tandem mass spectrometry of trypsinized samples, immunoprecipitated by the
      antibody from the TTLL10-expressing cells, we identified the 60-kDa protein as
      nucleosome assembly protein 1 (NAP1). Recombinant TTLL10 incorporated glycine
      into recombinant NAP1 in vitro. Mutational analyses indicated that Glu residues
      at 359 and 360 in the C-terminal part of NAP1 are putative sites for the
      modification. Thus, TTLL10 is a polyglycylase for NAP1.

PMID- 18331839
TI  - N-terminal cysteinyl proteins can be prepared using thrombin cleavage.
AB  - Expressed protein ligation--which allows native proteins to be selectively linked
      together by a normal peptide bond in an aqueous environment--has emerged as a
      powerful technique. The technique requires the formation of a C-terminal alpha
      thioester and an N-terminal Cys. An N-terminal Cys can be formed by enzymatic
      cleavage, commonly using the Factor Xa and TEV proteases. We show that thrombin
      can be used for the formation of N-terminal Cys, providing another choice of
      reagents for expressed protein ligation. Proteins with N-terminal Cys can be
      obtained by the convenient modification of vectors with the putative thrombin
      cleavage site LVPRG to LVPRC. Two example protein domains (Csk and Abl tyrosine
      kinase domain) with N-terminal Cys are demonstrated using this method. The use of
      thrombin protease to generate N-terminal Cys overcomes some of the limitations of
      existing methods, making it generally useful for expressed protein ligation and
      other biotechnological applications.

PMID- 18331840
TI  - Spectroelectrochemistry of P700 in native photosystem I particles and diethyl
      ether-treated thylakoid membranes from spinach and Thermosynechococcus elongatus.
AB  - The redox potentials (E(composite function')) of P700 in intact and diethyl ether
      treated thylakoid membranes as well as native photosystem (PS) I particles from
      spinach and Thermosynechococcus elongatus have been measured by a
      spectroelectrochemistry with an error range of +/-2-3 mV. Stepwise removal of
      antenna pigments by ether treatment caused distinct shifts of the E( composite
      function') value with increasing degree of water saturation in ether; negatively
      from +471 to +428 mV for spinach, but positively from +423 to +436 mV for T.
      elongatus. Such a contrasting behavior is discussed by invoking the mode of
      action of ether on the microenvironments around P700.

PMID- 18331841
TI  - Identification of new tyrosine phosphorylated proteins in rat brain mitochondria.
AB  - Reversible protein-phosphorylation is emerging as a key player in the regulation
      of mitochondrial functions. In particular tyrosine phosphorylation represents a
      promising field to highlight new mechanisms of bioenergetic regulation. Utilizing
      immunoaffinity enrichment of phosphotyrosine-containing peptides coupled to mass
      spectrometric analysis we detected new tyrosine phosphorylated proteins in rat
      brain mitochondria after peroxovanadate treatment. By bioinformatic predictions
      we provide suggestions about the potential role of tyrosine phosphorylation in
      mitochondrial physiology. Our results indicate a primary role of tyrosine
      phosphorylation in regulating energy production at the mitochondrial level.
      Moreover, tyrosine phosphorylation might regulate the mitochondrial membrane
      permeability targeting protein complexes containing ADP/ATP translocase, VDAC,
      creatine kinase and hexokinase.

PMID- 18331842
TI  - Inhibitory profile of a LEDGF/p75 peptide against HIV-1 integrase: insight into
      integrase-DNA complex formation and catalysis.
AB  - A lens epithelium-derived growth factor (LEDGF)/p75 peptide was evaluated for
      human immunodeficiency virus type 1 integrase (IN) inhibitory activity. The
      LEDGF/p75 peptide modestly inhibited IN catalysis and was dependent on IN-DNA
      assembly. The peptide was also effective at disrupting LEDGF/p75-IN complex
      formation. We next investigated the activity of the LEDGF/p75 peptide on IN
      mutant proteins that are unable to catalyze the DNA strand transfer reaction. The
      LEDGF/p75 peptide displayed an increased potency on these IN proteins, from 5
      fold to greater than 10-fold, indicating the IN multimeric state greatly
      influences the peptide inhibitory effects. These results shed light on IN-DNA
      multimeric formation, and how this process influences the LEDGF/p75-IN
      interaction.

PMID- 18331843
TI  - Localized cytosolic alkalization and its functional impact in ciliary cells.
AB  - Using confocal microscopy we demonstrate that ciliary cells from airway
      epithelium maintain two qualitatively distinct cytosolic regions in terms of pH
      regulation. While the bulk of the cytosol is stringently buffered and is
      virtually insensitive to changes in extracellular pH (pHo), the values of
      cytosolic pH in the vicinity of the ciliary membrane is largely determined by
      pHo. Variation of pHo from 6.2 up to 8.5 failed to affect ciliary beat frequency
      (CBF). Application of NH(4)Cl induced profound localized alkalization near cilia,
      which did not depress ciliary activity, but resulted in strong and prolonged
      enhancement of CBF. Calmodulin and protein kinase A (PKA) functionality was
      essential for the alkalization-induced CBF enhancement. We suggest that the
      ability of airway epithelium to sustain unusually strong but localized cytosolic
      alkalization near cilia facilitates CBF enhancement through altering the binding
      constants of Ca2+ to calmodulin and promotion of Ca2+-calmodulin complex
      formation. The NH4Cl-induced elevations in cytosolic pH and Ca2+ concentration
      act synergistically to activate calmodulin-dependent processes, cAMP pathway,
      and, thereby, stimulate CBF.

PMID- 18331844
TI  - Thioredoxins and glutaredoxins as facilitators of protein folding.
AB  - Thiol-disulfide oxidoreductase systems of bacterial cytoplasm and eukaryotic
      cytosol favor reducing conditions and protein thiol groups, while bacterial
      periplasm and eukaryotic endoplasmatic reticulum provide oxidizing conditions and
      a machinery for disulfide bond formation in the secretory pathway.
      Oxidoreductases of the thioredoxin fold superfamily catalyze steps in oxidative
      protein folding via protein-protein interactions and covalent catalysis to act as
      chaperones and isomerases of disulfides to generate a native fold. The active
      site dithiol/disulfide of thioredoxin fold proteins is CXXC where variations of
      the residues inside the disulfide ring are known to increase the redox potential
      like in protein disulfide isomerases. In the catalytic mechanism thioredoxin fold
      proteins bind to target proteins through conserved backbone-backbone hydrogen
      bonds and induce conformational changes of the target disulfide followed by
      nucleophilic attack by the N-terminally located low pK(a) Cys residue. This
      generates a mixed disulfide covalent bond which subsequently is resolved by
      attack from the C-terminally located Cys residue. This review will focus on two
      members of the thioredoxin superfamily of proteins known to be crucial for
      maintaining a reduced intracellular redox state, thioredoxin and glutaredoxin,
      and their potential functions as facilitators and regulators of protein folding
      and chaperone activity.

PMID- 18331845
TI  - Molecular crowding effects on structure and stability of DNA.
AB  - Living cells contain a variety of biomolecules including nucleic acids, proteins,
      polysaccharides, and metabolites as well as other soluble and insoluble
      components. These biomolecules occupy a significant fraction (20-40%) of the
      cellular volume. The total concentration of biomolecules reaches 400gL(-1),
      leading to a crowded intracellular environment referred to as molecular crowding.
      Therefore, an understanding of the effects of molecular crowding conditions on
      biomolecules is important to broad research fields such as biochemical, medical,
      and pharmaceutical sciences. In this review, we describe molecular conditions in
      the cytoplasm and nucleus, which are totally different from in vitro conditions,
      and then show the biochemical and biophysical consequences of molecular crowding.
      Finally, we discuss the effect of molecular crowding on the structure, stability,
      and function of nucleic acids and the significance of molecular crowding in
      biotechnology and nanotechnology.

PMID- 18331846
TI  - Computational design and evolution of the oscillatory response under light-dark
      cycles.
AB  - Circadian clocks are biological systems behaving as oscillators even in constant
      dark conditions. We propose to use a new strategy based on computational design
      to provide evidence on the origin and evolution of molecular clocks. We design
      synthetic molecular clocks having a reduced number of genes and some of them
      showing architectures found in nature. We analyse the response of our models
      under diverse forcing light-dark (LD) cycles. Our methodology allows us to evolve
      networks in silico using various selective pressures, which we apply to the
      analysis of clocks evolved to be either autonomous or phase locked. Our designed
      networks either have an oscillatory response with the same period as the forcing
      LD cycle, or they maintain their free-running period. Our methodology will allow
      analysing the automatic creation of a free-running period under various LD
      forcing functions and learning new design principles for circadian clocks.

PMID- 18331847
TI  - DNA triple helices: biological consequences and therapeutic potential.
AB  - DNA structure is a critical element in determining its function. The DNA molecule
      is capable of adopting a variety of non-canonical structures, including three
      stranded (i.e. triplex) structures, which will be the focus of this review. The
      ability to selectively modulate the activity of genes is a long-standing goal in
      molecular medicine. DNA triplex structures, either intermolecular triplexes
      formed by binding of an exogenously applied oligonucleotide to a target duplex
      sequence, or naturally occurring intramolecular triplexes (H-DNA) formed at
      endogenous mirror repeat sequences, present exploitable features that permit site
      specific alteration of the genome. These structures can induce transcriptional
      repression and site-specific mutagenesis or recombination. Triplex-forming
      oligonucleotides (TFOs) can bind to duplex DNA in a sequence-specific fashion
      with high affinity, and can be used to direct DNA-modifying agents to selected
      sequences. H-DNA plays important roles in vivo and is inherently mutagenic and
      recombinogenic, such that elements of the H-DNA structure may be
      pharmacologically exploitable. In this review we discuss the biological
      consequences and therapeutic potential of triple helical DNA structures. We
      anticipate that the information provided will stimulate further investigations
      aimed toward improving DNA triplex-related gene targeting strategies for
      biotechnological and potential clinical applications.

PMID- 18331849
TI  - Two nucleotide substitutions in the A-site of yeast 18S rRNA affect translation
      and differentiate the interaction of ribosomes with aminoglycoside antibiotics.
AB  - Two mutations in the A-site of 18S rRNA of Saccharomyces cerevisiae were
      investigated. The first, A1491G (rdn15), creates in yeast the same C1409-G1491
      base pair as in Escherichia coli and has behaved as an antisuppressor in genetic
      studies. Ribosomes from rdn15 are error-restrictive but their peptidyltransferase
      activity remains unchanged. The second mutation, U1495C (rdnhyg1), was initially
      isolated as a hygromycin-resistant mutation in Tetrahymena thermophila. We show
      that rdnhyg1 ribosomes are slightly error prone. Mutation rdnhyg1 does not affect
      catalytic activity, but it affects translocation, confirming the importance of
      nucleotide 1495 in the ratchet-like movement of the two subunits during
      translation. Paromomycin, an aminoglycoside antibiotic that binds to the
      ribosomal A-site, induces translational misreading and causes sensitivity to
      yeast cells. Mutation rdn15 is shown to be highly sensitive to both effects of
      paromomycin, while mutation rdnhyg1 is relatively resistant. Tobramycin, another
      aminoglycoside, does not affect the growth of yeast cells. Like paromomycin,
      however, it increases the error rate in rdn15 ribosomes relative to wild-type and
      decreases it in rdnhyg1 ribosomes. These mutations help define the role of two
      crucial sites in ribosome function and distinguish the modes of action of two
      aminoglycosides, a useful fact in the search for new strategies in drug design.

PMID- 18331848
TI  - In vivo veritas: using yeast to probe the biological functions of G-quadruplexes.
AB  - Certain guanine-rich sequences are capable of forming higher order structures
      known as G-quadruplexes. Moreover, particular genomic regions in a number of
      highly divergent organisms are enriched for such sequences, raising the
      possibility that G-quadruplexes form in vivo and affect cellular processes. While
      G-quadruplexes have been rigorously studied in vitro, whether these structures
      actually form in vivo and what their roles might be in the context of the cell
      have remained largely unanswered questions. Recent studies suggest that G
      quadruplexes participate in the regulation of such varied processes as telomere
      maintenance, transcriptional regulation and ribosome biogenesis. Here we review
      studies aimed at elucidating the in vivo functions of quadruplex structures, with
      a particular focus on findings in yeast. In addition, we discuss the utility of
      yeast model systems in the study of the cellular roles of G-quadruplexes.

PMID- 18331850
TI  - Age-related alterations in oxidatively damaged proteins of mouse heart
      mitochondrial electron transport chain complexes.
AB  - Mitochondrially generated ROS increase with age and are a major factor that
      damages proteins by oxidative modification. Accumulation of oxidatively damaged
      proteins has been implicated as a causal factor in the age-associated decline in
      tissue function. Mitochondrial electron transport chain (ETC) complexes I and III
      are the principle sites of ROS production, and oxidative modifications to their
      complex subunits inhibit their in vitro activity. We hypothesize that
      mitochondrial complex subunits may be primary targets for modification by ROS,
      which may impair normal complex activity. This study of heart mitochondria from
      young, middle-aged, and old mice reveals that there is an age-related decline in
      complex I and V activity that correlates with increased oxidative modification to
      their subunits. The data also show a specificity for modifications of the ETC
      complex subunits, i.e., several proteins have more than one type of adduct. We
      postulate that the electron leakage from ETC complexes causes specific damage to
      their subunits and increased ROS generation as oxidative damage accumulates,
      leading to further mitochondrial dysfunction, a cyclical process that underlies
      the progressive decline in physiologic function of the aged mouse heart.

PMID- 18331851
TI  - New directions in library design and analysis.
AB  - The high costs associated with high-throughput screening (HTS) coupled with the
      limited coverage and bias of current screening collections is such that diversity
      analysis continues to be an important criterion in lead generation. Whereas early
      approaches to diversity analysis were based on traditional descriptors such as
      two-dimensional fingerprints a recent emphasis has been on assessing scaffold
      coverage to ensure that a variety of different chemotypes are represented.
      Moreover, whether designing diverse or focused libraries, it is widely recognised
      that designs should aim to achieve a balance in a number of different properties
      and multiobjective optimisation provides an effective way of achieving such
      designs.

PMID- 18331852
TI  - Mining in chemometrics.
AB  - Some of the increasingly spread data mining methods in chemometrics like
      exploratory data analysis, artificial neural networks, pattern recognition, and
      digital image processing with their highs and lows along with some of their
      representative applications are discussed. The development of more complex
      analytical instruments and the need to cope with larger experimental data sets
      have demanded for new approaches in data analysis, which have led to advanced
      methods in experimental design and data processing. Hypothesis-driven methods
      typified by inferential statistics have been gradually complemented or even
      replaced by data-driven model-free methods that seek for structure in data
      without reference to the experimental protocol or prior hypotheses. The emphasis
      is put on the ability of data mining methods to solve multivariate-multiresponse
      problems on the basis of experimental data and minimal statistical assumptions
      only, in contrast to classical methods, which require predefined priors to be
      tested against some null-hypothesis.

PMID- 18331853
TI  - An entropy-based method for noise reduction of liquid chromatography-mass
      spectrometry data.
AB  - Entropy-based methods have been extensively used to measure the uncertainty
      information in a variety of fields. In this article, a novel information theory
      based method for reducing noise of liquid chromatography-mass spectrometry
      (LC/MS) data was developed. The uncertainty existed in the LC/MS chromatograms
      was captured and evaluated by information entropy. By comparing the information
      entropy computationally derived from mass chromatograms, the good quality
      chromatograms and the noisy chromatograms can be distinguished. The proposed
      method was applied in processing LC/MS data of "Jing-Zhi-Guan-Xin" troche which
      is a well-known preparation of traditional Chinese medicine (TCM). The obtained
      result indicated that this method is beneficial to reduce noise of LC/MS data of
      complicated chemical samples, such as TCM.

PMID- 18331854
TI  - Bioelectrochemical immunoassay of polychlorinated biphenyl.
AB  - A simple, rapid, and highly sensitive bioelectrochemical immunoassay method based
      on magnetic beads (MBs) and disposable screen-printed electrodes (SPE) has been
      developed to detect polychlorinated biphenyls (PCBs). The principle of this
      bioassay is based on a direct competitive enzyme-linked immunosorbent assay using
      PCB-antibody-coated MBs and horseradish peroxidase (HRP)-labeled PCB (HRP-PCB). A
      magnetic process platform was used to mix and shake the samples during the
      immunoreactions and to separate free and unbound reagents after the liquid-phase
      competitive immunoreactions among PCB-antibody-coated MBs, PCB analyte, and HRP
      PCB. After a complete immunoassay, the HRP tracers attached to MBs were
      transferred to a substrate solution containing o-aminophenol and hydrogen
      peroxide for electrochemical detection. The different parameters, including the
      amount of HRP-PCB conjugates, immunoreaction time, and the concentration of
      substrate that governs the analytical performance of the immunoassay have been
      studied in detail and optimized. The detection limit of 10 gmL(-1) was obtained
      under optimum experimental conditions. The performance of this bioelectrochemical
      immunoassay was successfully evaluated with untreated river water spiked with
      PCBs, and the results were validated by commercial PCB enzyme-linked
      immunosorbent assay kit, indicating that this convenient and sensitive technique
      offers great promise for decentralized environmental application and trace PCBs
      monitoring.

PMID- 18331855
TI  - A highly sensitive amperometric sensor for oxygen based on iron(II)
      tetrasulfonated phthalocyanine and iron(III) tetra-(N-methyl-pyridyl)-porphyrin
      multilayers.
AB  - The development of a highly sensitive sensor for oxygen is proposed using a
      glassy carbon (GC) electrode modified with alternated layers of iron(II)
      tetrasulfonated phthalocyanine (FeTsPc) and iron(III) tetra-(N-methyl-pyridyl)
      porphyrin (FeT4MPyP). The modified electrode showed excellent catalytic activity
      for the oxygen reduction. The reduction potential of the oxygen was shifted about
      330 mV toward less negative values with this modified electrode, presenting a
      peak current much higher than those observed on a bare GC electrode. Cyclic
      voltammetry and rotating disk electrode (RDE) experiments indicated that the
      oxygen reduction reaction involves 4 electrons with a heterogenous rate constant
      (k(obs)) of 3x10(5) mol(-1) L s(-1). A linear response range from 0.2 up to 6.4
      mg L(-1), with a sensitivity of 4.12 microA L mg(-1) (or 20.65 microA cm(-2) L
      mg(-1)) and a detection limit of 0.06 mg L(-1) were obtained with this sensor.
      The repeatability of the proposed sensor, evaluated in terms of relative standard
      deviation (R.S.D.) was 2.0% for 10 measurements of a solution of 6.4 mg L(-1)
      oxygen. The sensor was applied to determine oxygen in pond and tap water samples
      showing to be a promising tool for this purpose.

PMID- 18331856
TI  - Application of liquid-liquid-liquid microextraction and high-performance liquid
      chromatography for the determination of sulfonamides in water.
AB  - This work presents a novel liquid-liquid-liquid microextraction (LLLME) technique
      for the extraction of sulfonamides from aqueous systems; it combines with high
      performance liquid-chromatography-ultraviolet absorbance detection (HPLC/UV). In
      this experiment the sulfonamides were successively extracted from a donor phase
      (i.e., a water sample) into several microliters of an organic phase and then from
      the organic phase into an acceptor phase (i.e., an aqueous extract) by LLLME. The
      following separation and quantitative analyses were performed using HPLC/UV with
      265 nm detection. Extraction condition such as solvent identity, agitation,
      extraction time, acceptor phase NaOH concentration, donor phase pH, and salt
      addition were optimized. Relative standard deviation (RSD, 2.6-5.3%), coefficient
      of estimation (R2, 0.9972-0.9999), and method detection limit (MDL, 0.11-0.77 ng
      mL(-1)) were achieved under the selected conditions. The proposed method was
      successfully applied to the analyses of three practical water samples and the
      relative recoveries of sulfonamides from the spiked water samples were in the
      range of 86.2-108.7%. The proposed method also confirms microextraction to be
      robust to monitoring trace levels of sulfacetamide, sulfadiazine, sulfathiazole,
      sulfamerazine, sulfadimidine, sulfamonomethoxine, sulfamethoxazole, and
      sulfaquinoxaline in aqueous samples.

PMID- 18331857
TI  - Comparison of low-level polycyclic aromatic hydrocarbons in sediment revealed by
      Soxhlet extraction, microwave-assisted extraction, and pressurized liquid
      extraction.
AB  - We analyzed polycyclic aromatic hydrocarbons (PAHs) present in lake sediment at
      low levels (<1 microg g(-1)) by using Soxhlet extraction (Soxhlet), microwave
      assisted extraction (MAE), and pressurized liquid extraction (PLE) in combination
      with gas chromatography and isotope-dilution mass spectrometry. Although all
      extraction techniques showed good repeatability for five target PAHs (relative
      standard deviation <5.2%, n=3), the results decreased in the order
      PLE>MAE>Soxhlet. Differences in the results originated mainly from differences in
      the extraction efficiencies of the techniques for native PAHs, because all
      techniques gave comparable recovery yields of corresponding 13C-labeled PAHs (13C
      PAHs) (51-84%). Since non-negligible amounts of both native PAHs and 13C-PAHs
      were re-adsorbed on matrix in MAE, not only recovery yields of 13C-PAHs but also
      efficiencies of extraction of native PAHs should be examined to evaluate the
      appropriateness of any analytical procedures.

PMID- 18331858
TI  - Spectrophotometric determination of cyclotrimethylenetrinitramine (RDX) in
      explosive mixtures and residues with the Berthelot reaction.
AB  - On-site colorimetric methods are a valuable, cost-effective tool to assess the
      nature and extent of contamination in remediated sites and to enable on-site
      screening for police criminology laboratories. The existing colorimetric method
      for cyclotrimethylenetrinitramine (RDX) based on a Griess reaction suffers from
      the non-quantitative reduction to nitrite and from the unstable character of HNO2
      in acidic medium. Thus we propose a novel spectrophotometric RDX assay in
      explosive mixtures and residues, based on (Zn+HCl) reduction of RDX in a
      microwave oven, followed by neutralization of the reduction products to ammonia
      and low molecular-weight amines, and Berthelot reaction of these amine-compounds
      with phenol and hypochlorite in alkaline medium to give an intensely blue
      indophenol dye absorbing at 631nm. The molar absorptivity and limit of detection
      (LOD) for RDX were (1.08+/-0.04)x10(4) L mol(-1) cm(-1) and 0.18 mg L(-1),
      respectively. Application of the method to synthetic mixture solutions of RDX and
      trinitrotoluene (TNT) at varying proportions showed that there was minimal
      interference from TNT (which could be compensated for by dicyclohexylamine
      colorimetry), since the Berthelot reaction was essentially non-responsive to m
      substituted anilines derived from TNT upon (Zn+HCl) reduction. The proposed
      method was successfully applied to military-purpose explosive mixtures of
      (RDX+inert matter) such as Comp A5, Comp C4, and Hexal P30, and to (RDX+TNT)
      mixtures such as Comp B. The molar absorptivity of RDX was much higher than that
      of either ammonium or nitrate; RDX could be effectively separated from ammonium
      and nitrate in soil mixtures, based on solubility differences. The Berthelot
      method for RDX was statistically validated using Comp B mixtures against standard
      HPLC equipped with a Hypersil C-18 column with (40% MeOH-60% H2O) mobile phase,
      and against gas chromatography-thermal energy analysis (GC-TEA) system.

PMID- 18331859
TI  - Molecularly imprinted polymer based potentiometric sensor for the determination
      of hydroxyzine in tablets and biological fluids.
AB  - Molecular imprinting is a useful technique for the preparation of functional
      materials with molecular recognition properties. In this work, a biomimetic
      potentiometric sensor, based on a non-covalent imprinted polymer, was fabricated
      for the recognition and determination of hydroxyzine in tablets and biological
      fluids. The molecularly imprinted polymer (MIP) was synthesized by precipitation
      polymerization, using hydroxyzine dihydrochloride as a template molecule,
      methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylat
      (EGDMA) as a cross-linking agent. The sensor showed a high selectivity and a
      sensitive response to the template in aqueous system. The MIP-modified electrode
      exhibited a Nernstian response (29.4+/-1.0 mV decade(-1)) in a wide concentration
      range of 1.0x10(-6) to 1.0x10(-1) M with a lower detection limit of 7.0x10(-7) M.
      The electrode demonstrated a response time of approximately 15s, a high
      performance and a satisfactory long-term stability (more than 5 months). The
      method has the requisite accuracy, sensitivity and precision to assay hydroxyzine
      in tablets and biological fluids.

PMID- 18331860
TI  - A novel approach based on ferricyanide-mediator immobilized in an ion
      exchangeable biosensing film for the determination of biochemical oxygen demand.
AB  - A novel biochemical oxygen demand (BOD) sensing method employing a ferricyanide
      (FC) mediator immobilized in an ion-exchangeable polysiloxane was developed. The
      ion-exchangeable polysiloxane containing alkylammonium groups (PAPS-Cl) was
      synthesized by sol-gel reaction of 3-(aminopropyl)trimethoxysilane (APTMOS)
      catalyzed by hydrochloric acid. FC was combined in PAPS-Cl via ion-association
      and the product was labeled as PAPS-FC, which was employed for a modified glassy
      carbon electrode. The apparent diffusion coefficient (D(app)) of FC on the
      modified glassy carbon electrode was 9.8x10(-11) cm(2) s(-1). In a three
      electrode system, a linear relationship between the anodic current responses and
      glucose/glutamate (GGA) concentration was obtained up to 40 mg O2 L(-1) (r=0.994)
      when the reaction mixture was incubated for 30 min. Single sensor and piece-to
      piece reproducibility were less than 3.8 and 7.7%, respectively. The effects of
      dissolved oxygen, pH, temperature and co-existing substances on the BOD responses
      were studied. The sensor responses to nine pure organic substances were compared
      with the conventional BOD5 method and other biosensor methods. Detection results
      of seawater samples were compared with those obtained from the BOD5 method and
      showed a good correlation (r=0.988).

PMID- 18331861
TI  - A liposome immune lysis assay for enrofloxacin in carp and chicken muscle.
AB  - A homogenous complement-mediated liposome immune lysis assay (LILA) was developed
      for the determination of enrofloxacin (ENRO) in carp and chicken muscle. ENRO was
      covalently coupled to DPPE, and then immobilized onto the surface of liposomes by
      reverse-phase evaporation method. The performed liposome would be specifically
      lysed by the sequential additions of anti-ENRO monoclonal antibody (MAb) and
      guinea pig complement. Through a competitive assay format, the performed liposome
      can be used to detect ENRO in a range of 5.0-20 ng mL(-1) in assay buffer. The
      limit of detection of ENRO in carp and chicken muscle was 1 ng g(-1) and the
      limit of quantification was 2 ng g(-1). Recoveries ranged from 58.3% to 65.2% for
      carp and 55.6-63.8% for chicken muscle at spiked levels of 2-8 ng g(-1), with
      intra-assay and inter-assay variations 5.6-12.3% and 7.1-19.2%, respectively.

PMID- 18331862
TI  - Simultaneous voltammetric detection of ascorbic acid, dopamine and uric acid
      using a pyrolytic graphite electrode modified into dopamine solution.
AB  - Pyrolytic graphite electrodes (PGE) were modified into dopamine solutions using
      phosphate buffer solutions, pH 10 and 6.5, as supporting electrolyte. The
      modification process involved a previous anodization of the working electrode at
      +1.5 V into 0.1 mol L(-1) NaOH followed by other anodization step, in the same
      experimental conditions, into dopamine (DA) solutions. pH of the supporting
      electrolyte performed an important role in the production of a superficial
      melanin polymeric film, which permitted the simultaneous detection of ascorbic
      acid (AA), (DA) and uric acid (UA), DeltaE(AA-DA)=222 mV; DeltaE(AA-UA)=360 mV
      and DeltaE(DA-UA)=138 mV, avoiding the superficial poisoning effects. The
      calculated detection limits were: 1.4x10(-6) mol L(-1) for uric acid, 1.3x10(
      5)molL(-1) for ascorbic acid and 1.1x10(-7) mol L(-1) for dopamine, with
      sensitivities of (7.7+/-0.5), (0.061+/-0.001) and (9.5+/-0.05) A mol(-1) cm(-2),
      respectively, with no mutual interference. Uric acid was determined in urine,
      blood and serum human samples after dilution in phosphate buffer and no
      additional sample pre-treatment was necessary. The concentration of uric acid in
      urine was higher than the values found in blood and serum and the recovery tests
      (92-102%) indicated that no matrix effects were observed.

PMID- 18331863
TI  - Preliminary evaluation of new polymer matrix for solid-phase extraction of
      nonylphenol from water samples.
AB  - Molecularly imprinted (MIP) and blank polymers with affinity for nonylphenol were
      designed using computational modelling. Chromatographic tests demonstrated higher
      affinity of imprinted polymers towards the template nonylphenol as compared with
      blank polymers. The performance of both polymers in solid-phase extraction was
      however very similar. Both blank and imprinted polymers appeared to be suitable
      for the removal and pre-concentration of nonylphenol from contaminated water
      samples with 99% efficiency of the recovery. The commercial resins PH(EC)
      (Biotage) and C18 (Varian) tested in the same conditions used for comparative
      purposes had recovery rate <84%. The polymer capacity for nonylphenol was 231 mg
      g(-1) for blank and 228 mg g(-1) for MIP. The synthesised materials can have
      significance for sample pre-concentration and environmental analysis of this
      class of compounds.

PMID- 18331864
TI  - Narrowly dispersed molecularly imprinted microspheres prepared by a modified
      precipitation polymerization method.
AB  - A modified precipitation polymerization (MPP) method was established to prepare
      narrowly dispersed molecularly imprinted polymeric microspheres. MPP was
      stabilizer and surfactant free and needed only small amount of porogen (about 50
      wt.%). Only part of alcohols and all the alkanes tested formed particles. Using a
      mixture of alkane and toluene as porogen, the carbon numbers of alkanes and
      solubility parameter of porogenic solvents were important factors in controlling
      particle morphology. Nearly mono-dispersed microspheres with diameter of about 2
      3 microm were synthesized by MPP using mineral oil:toluene=2:3 as porogen.
      Template did not affect the formation of globe microspheres in MPP. Microspheres
      prepared under the lowest reaction temperature had the highest binding
      capability. When used as sorbents of high performance liquid chromatography
      (HPLC), the microspheres prepared by MPP using bisphenol A, estradiol, and
      tebuconazole as template had similar binding selectivity and higher binding
      capability compared to microspheres synthesized by classical precipitation
      polymerization. Photoinitiation and low reaction temperature were important
      factors attributed to better binding capability of microspheres prepared by MPP.

PMID- 18331865
TI  - Precise determination of cadmium and lead isotopic compositions in river
      sediments.
AB  - A method for the accurate determination of Cd and Pb isotope compositions in
      sediment samples is presented. Separation of Cd and Pb was designed by using an
      anionic exchange chromatographic procedure. Measurements of Cd isotopic
      compositions were carried out by multi-collector inductively coupled plasma mass
      spectrometer (MC-ICPMS), by using standard-sample bracketing technology for mass
      bias correction and Pb isotopic ratios were determined by thermal ionization mass
      spectrometry (TIMS). The factors that affect the accurate and precise Cd isotope
      compositions analysis, such as instrumental mass fractionation and isobaric
      interferences, were carefully evaluated and corrected. The Cd isotopic results
      were reported relative to an internal Cd solution and expressed as the
      delta(114/110)Cd. Five Cd reference solutions and one Pb standard were repeatedly
      measured in order to assess the accuracy of the measurements. Uncertainties
      obtained were estimated to be lesser than 0.11 per thousand (2s) for the
      delta(114/110)Cd value. Analytical uncertainties in 2s for Pb isotopic ratios
      were better than 0.5 per thousand. The method has been successfully applied to
      the investigation of Cd and Pb isotope compositions in sediment samples collected
      from North River in south China.

PMID- 18331866
TI  - Abstracts of the 63rd Annual Scientific Convention and Meeting of the Society of
      Biological Psychiatry, Washington, DC, USA, 2008.

PMID- 18331867
TI  - Clinical factors affecting endometrial receptiveness in oocyte donation cycles.
AB  - OBJECTIVE: To provide a summary of the actual knowledge about the clinical
      factors affecting the oocyte recipient (other than those associated with uterine
      cavity abnormalities) on the outcome of oocyte donation cycles. DESIGN: Review of
      the literature. SETTING: Information regarding the association between age, body
      mass index (BMI), endometrial priming, tobacco consumption, hydrosalpinx, and
      endometriosis/adenomyosis in oocyte recipients and the results of oocyte donation
      cycles. RESULT(S): Recipient age and the presence of hydrosalpinx are clearly
      associated with a poorer outcome in oocyte donation cycles. The negative impact
      of tobacco consumption has recently been confirmed. The exact relevance of an
      elevated BMI is under debate but it is likely that it determines a lower ongoing
      pregnancy rate (PR). Endometriosis may be significant for endometrial
      receptiveness in the context of a natural cycle, but no negative impact is
      detected when standard endometrial priming protocols are used in oocyte donation.
      The same may be true for adenomyosis, although its relevance to endometrial
      receptiveness is less clear. CONCLUSION(S): Accumulated knowledge in the field of
      oocyte donation has led to the recognition of clinical variables that affect
      cycle outcome by impairing endometrial receptiveness. Many studies are being
      carried out on endometrial molecular and gene expression changes taking place in
      these circumstances. In the near future a comprehensive understanding of these
      processes should be achieved, from a genetic, molecular, and clinical
      perspective. These advances in the collective knowledge will lead to an
      improvement in the diagnosis and treatment of infertile patients.

PMID- 18331868
TI  - Tobacco and fertility: our responsibilities.
AB  - Publication of the new US Public Health Service-sponsored Clinical Practice
      Guideline, Treating Tobacco Use and Dependence: 2008, coupled with the persistent
      prevalence of tobacco use in the reproductive-age population and the negative
      effect of tobacco on fertility, prompts an updated review of this topic, geared
      to those who treat infertility.

PMID- 18331869
TI  - Markov modeling: questionable data in, questionable data out.

PMID- 18331870
TI  - Introduction to the Proceedings of the Fifth European Conference on Comparative
      Neurobiology: evolution and the generation of novelties in the nervous system.

PMID- 18331871
TI  - Forebrain evolution in bony fishes.
AB  - The bony fishes consist of ray-finned fishes and lobe-finned fishes. In ray
      finned fishes, the forebrain forms a morphocline from the cladistian bichirs
      through teleosts regarding the number and increasing complexity of pallial
      connections. The nuclei of the posterior tubercle parallel this increase in
      complexity, but the dorsal thalamic nuclei do not. The primary targets of the
      dorsal thalamic nuclei are the subpallial nuclei, whereas the primary targets of
      the posterior tubercle are various pallial divisions. Primitively, nucleus
      medianus is the primary projection nucleus of the posterior tubercle. It is
      either reduced or lost in teleosts, and its role is taken over by the
      preglomerular complex, which appears to develop from proliferative zones in both
      the thalamic alar plate and the posterior tubercle. Although there are numerous
      hodological data for the pallium in ray-finned fishes, there is no consensus
      regarding its homologies with other vertebrates. In contrast to ray-finned
      fishes, very few experimental data exist for lobe-finned fishes. The coelacanth,
      Latimeria, is extremely rare, and lungfishes are the best source for new
      experimental data. At this point, there are sufficient data to suggest that
      lungfishes are characterized by a pallium that is divided into four components,
      separate dorsal and ventral striatopallidal systems, and an amygdala that
      consists of anterior, central, lateral, and medial nuclei. The data suggest that
      telencephalic organization in lungfishes is far more similar to that in
      amphibians than was previously suspected.

PMID- 18331872
TI  - Two interconnected functional systems in the amygdala of amniote vertebrates.
AB  - The amygdala shows ventropallial and lateropallial derivatives that can be
      compared among vertebrates according to their topological position, either
      superficial (cortical amygdala) or deep (basolateral amygdala and amygdalo
      hippocampal area), connections and histochemical features. On the other hand, the
      subpallial amygdala, also called extended amygdala, is composed of medial and
      central divisions. In mammals, both divisions consist of an intra-amygdaloid
      portion and a part of the bed nucleus of the stria terminalis. In non-mammals,
      the intratelencephalic trajectory of the stria terminalis is short and both poles
      of the extended amygdala are close together. Like its mammalian counterpart, the
      medial extended amygdala of non-mammals receives an olfactory input (reduced in
      birds), projects to the medial hypothalamus and shows a sexually dimorphic
      vasotocinergic (vasopressinergic) cell group. Thus, the medial extended amygdala
      is part of the forebrain circuitry for the expression of defensive and
      reproductive behaviours. In turn, the central extended amygdala of amniotes shows
      a prominent CGRP innervation and a medially located CRF/neurotensin-expressing
      cell group, and projects to the lateral hypothalamus and to the midbrain and
      brainstem centres involved in fear/anxiety expression. The projections from the
      pallial amygdala to the central and medial extended amygdala are similarly
      organized in the mammals and non-mammals. These circuits, which have not changed
      substantially in birds despite the disappearance of the vomeronasal system,
      delineate two functional divisions within the amygdala that, together,
      orchestrate the expression of species-specific behaviours with a strong emotional
      component.

PMID- 18331873
TI  - Distinct immunohistochemically defined areas in the medial amygdala in the
      developing and adult mouse.
AB  - The medial amygdala has been considered a subpallial structure, but various
      studies have shown that is a somewhat complex structure expressing both pallial
      and subpallial gene markers. In this regard, we analyzed the immunohistochemical
      expression of the neurotransmitter GABA, the vesicular glutamate transporter type
      2 (VGLUT2), the neuronal nitric oxide synthase (nNOS), and the calcium-binding
      proteins calbindin-D28k (CB) and calretinin (CR) in the developing and adult
      mouse medial amygdala. From intermediate embryonic stages on, neurochemical data
      show a distinctive superficial region forming a band all along the medial
      amygdalar surface. This superficial band displays a strong VGLUT2-immunoreactive
      neuropil and numerous CR-immunoreactive fibers, as well as some nNOS-, CR- or CB
      positive cells. In contrast, the superficial region of the posterior medial
      amygdala appears to be non-GABA immunoreactive. This band in the posterior medial
      amygdala matches a Tbr1-expressing territory. Our results also show differences
      between dorsal and ventral parts of the postnatal and adult posterior medial
      amygdala. Especially, a compact cell aggregate of nNOS immunoreactive cells was
      found in the ventral portion of the medial amygdala, whereas the dorsal part is
      occupied by scattered weakly stained cells. Comparison of our results with gene
      expression patterns and fiber-tracing studies, let us to propose that the
      superficial band is a pallial derivative, whereas the dorsal and ventral nuclei
      of the posterior medial amygdala receive each neurons from different subpallial
      compartments, and the latter one a subset of excitatory, pallial projection
      neurons.

PMID- 18331874
TI  - Brain segmentation and trigeminal projections in the lamprey; with reference to
      vertebrate brain evolution.
AB  - Vertebrate brains exhibit remarkable diversity in each animal group, reflecting
      evolutionary changes at the molecular-level developmental program of the nervous
      system that vertebrates have experienced. We focused on the developmental
      morphological plan of the brain to understand the evolutionary scenario that led
      to the above diversity. By comparing the organization of the brain of non
      vertebrate chordates, cyclostomes and gnathostomes, a step-wise modification of
      brain patterning programs becomes apparent. Furthermore, by labeling the lamprey
      oral region, the somatotopic projections of the trigeminal nerve that enter into
      the hindbrain become visible. Finally, by combining the knowledge on rhombomere
      segments and neuronal projections, the evolutionary relationship between
      somatotopy and brain segmentation are discussed.

PMID- 18331875
TI  - Conserved non-coding sequences and transcriptional regulation.
AB  - Genes coding for transcription factors and developmental regulators have a high
      likelihood to harbour cis-regulatory regions that are structurally conserved
      among orthologous genes in the vertebrate lineage. These regions can span up to
      several hundred basepairs with 70 and more percent sequence identity between fish
      and mammals. Even though this conservation is an efficient tool to discover cis
      regulatory regions, we know little about why these specific genes maintain such
      highly conserved regulatory sequences. Here, we summarise work of the past few
      years on the regulatory modules of the sonic hedgehog and neurogenin1 genes. We
      will discuss the high sequence conservation of the regulatory elements in the
      context of models of enhancer evolution. Our data suggest that conservation of
      sequence does not necessarily imply a conserved function in other vertebrates.

PMID- 18331876
TI  - Conserved pattern of OTP-positive cells in the paraventricular nucleus and other
      hypothalamic sites of tetrapods.
AB  - The paraventricular nucleus complex (Pa) is a component of central neural
      circuitry that regulates several homeostatic variables. The paraventricular
      nucleus is composed of magnocellular neurons that project to the posterior
      pituitary and parvicellular neurons that project to numerous sites in the central
      nervous system. According to the revised prosomeric model, the paraventricular
      nucleus is located caudal to the eye stalk along the rostrocaudal dimension of
      the dorsal hypothalamic alar plate. Caudally, the paraventricular nucleus abuts
      the prethalamus (prosomere 3), and the entire complex is flanked ventrally and
      dorsally by Dlx5-expressing domains of the alar plate. The homeodomain
      transcription factor Orthopedia (Otp) is expressed in several separate
      hypothalamic sites: the paraventricular nucleus, perimammillary region and
      arcuate nucleus. In this study, we compared Otp expression in the hypothalamus of
      mouse (Mus musculus), chick (Gallus gallus), frog (Rana perezi) and axolotol
      (Ambystoma mexicanum), using immunohistochemical and in situ hybridization
      techniques. In all cases, Otp-positive cells in the paraventricular nucleus were
      excluded from Dlx5-expressing adjacent domains. Other positive neuronal
      populations were observed in the arcuate nucleus and oblique perimammillary band.
      Expression in the medial amygdala appears to be continuous with the Otp
      expressing paraventricular nucleus complex. This area is relatively unevaginated
      in the amphibian brains, barely evaginated in the chick, and fully evaginated in
      the mouse. These data led us to conclude that the expression pattern of Otp is
      topologically highly conserved in tetrapods and is plesiomorphic among chordates.

PMID- 18331877
TI  - The segmental organization of the developing shark brain based on neurochemical
      markers, with special attention to the prosencephalon.
AB  - Brain regionalization has been extensively studied in tetrapods, teleosts and
      cyclostomes. In contrast, it has not been investigated in elasmobranchs, despite
      their key phylogenetic position to understand brain evolution in jawed
      vertebrates. In this study we provide a schematic view of the segmental pattern
      of the developing shark brain based on mapping of the expression of Pax6 and
      neurochemical markers such as calretinin, tyrosine hydroxylase, serotonin, and
      glutamic acid decarboxylase. By correlating the cytoarchitectonic limits with the
      specific location of these markers, we identify transverse and longitudinal
      boundaries and domains, which suggest a segmental pattern, reminiscent of the one
      described in other vertebrates. Taken together, these data provide an initial
      scheme, which will be further tested and refined using a broader range of genetic
      markers involved in patterning and differentiation.

PMID- 18331878
TI  - Anuran olfactory bulb organization: embryology, neurochemistry and hodology.
AB  - In Xenopus laevis, we analyzed the origin of the projection neurons and
      interneurons in the developing olfactory bulbs by studying the expression
      patterns of the genes x-Eomes, x-Lhx5, x-Dll3 and x-Pax6. Olfactory bulb
      interneurons were characterized by using four conserved molecular markers for
      distinct subpopulations: gamma-aminobutyric acid, calretinin, calbindin, and
      tyrosine hydroxylase. Immunohistochemistry was combined with tract-tracing
      experiments to demonstrate the projection neurons and the interneurons of the
      olfactory bulbs simultaneously. Taken together, the results showed: (1) the
      pallial nature of the olfactory bulb and its projection neurons in Xenopus, like
      in mammals with comparable central projection areas, (2) the subpallial origin of
      the interneurons that, most likely, follow migratory pathways comparable to those
      described for mammals, (3) the different interneuron types possess neurochemical
      characteristics similar to mammals. Therefore, the present results show that the
      origin, chemoarchitecture and central connections of the olfactory bulbs are
      highly conserved in evolution.

PMID- 18331879
TI  - Aspartate immunoreactivity in the telencephalon of the adult sea lamprey:
      comparison with GABA immunoreactivity.
AB  - The excitatory amino acid l-aspartate (Asp) plays a number of roles in neuronal
      function. We studied the distribution of Asp-immunoreactive (ir) cells in the
      telencephalon of young and upstream migrating adult sea lamprey, Petromyzon
      marinus, and compared it with the distribution of gamma-aminobutyric acid (GABA)
      immunoreactivity, by using double immunofluorescence methods. Our results reveal
      for the first time the existence of Asp-ir neuronal populations in the lamprey
      forebrain. In the olfactory bulbs, Asp-ir neurons were observed in the mitral
      cell layer and in the inner cellular layer. Many granule-like cells were both Asp
      ir and GABA-ir. In the pallium, Asp-ir cells were abundant in the lateral pallium
      and most of them were also GABA-ir. In the septum/terminal lamina nucleus, some
      cerebrospinal fluid-contacting type (CSF-c) cells were either Asp-ir or GABA-ir,
      and a few were double-labeled. Some non-CSF-c septal cells were both Asp-ir and
      GABA-ir. In the striatum, Asp-ir and/or GABA-ir cells were either subependymal or
      located in the characteristic arched cell row. In the lateral preoptic region, a
      few small Asp-ir/GABA-ir neurons were observed. In the caudal preoptic recess
      nucleus, numerous CSF-c cells were Asp-ir and/or GABA-ir. This study also reveals
      that colocalization of GABA and Asp immunoreactivities in telencephalic neurons
      is partial. Further investigation is required to establish whether Asp is a
      neurotransmitter and/or an intermediate in GABA synthesis in lamprey
      telencephalon.

PMID- 18331880
TI  - The organization of the pretectal nuclei in the trout: a revision based on
      experimental holodogical studies.
AB  - The neuronal tracer DiI was applied to different brain centers of the rainbow
      trout in order to study the connections of pretectal nuclei. Our results showed
      that some pretectal nuclei receive a direct projection from the contralateral
      retina: the parvocellular superficial pretectal nucleus, the central pretectal
      nucleus, the intermediate pretectal nucleus and the ventral accessory optic
      nucleus. In turn, the central pretectal, the intermediate pretectal and the
      ventral accessory optic nuclei, together with the paracommissural nucleus,
      project to the cerebellum and the torus longitudinalis. The magnocellular
      superficial pretectal nucleus does not receive retinal projections, but receives
      ipsilateral projections from the optic tectum and the mesencephalic tegmentum. In
      turn, it projects to the ipsilateral oculomotor nucleus and lateral nucleus of
      the valvula. The posterior pretectal nucleus and the parvocellular superficial
      pretectal nucleus receive afferents from the ipsilateral nucleus isthmi. The
      posterior pretectal nucleus projects to the inferior hypothalamic lobe. Our
      results reveal a conspicuous projection from the ipsilateral parvocellular
      superficial pretectal nucleus to the contralateral one and also to the
      contralateral posterior prectectal nucleus, not reported in previous experimental
      studies of teleosts. Pretectal centers appear to integrate visual/optic-related
      centers mainly with the hypothalamus and the cerebellum. The organization of the
      trout pretectum was compared with the pretectal organization patterns proposed in
      various teleosts.

PMID- 18331881
TI  - Immunohistochemical localization of neuropeptide FF-like in the brain of the
      turtle: relation to catecholaminergic structures.
AB  - A previous study in the lizard Gekko gecko has revealed that neuropeptide FF
      (NPFF, a neuropeptide involved in nociception, cardiovascular regulation, and
      endocrine function) is widely distributed throughout the brain and spinal cord.
      Although the distribution of NPFF immunoreactivity shares many features with that
      found in other vertebrates, it was noted that Gekko shared more features with
      anamniotes in terms of number of cell groups, more elaborate networks of fibers,
      and lack of colocalization with catecholamines, than with mammals. To assess the
      primitive or derived character of these features, NPFF and tyrosine hydroxylase
      (TH) antibodies have been applied to the brain and spinal cord of the turtle,
      Pseudemys scripta elegans, which belongs to a different radiation of reptiles. As
      in Gekko, major NPFF-ir cell groups were found in the diagonal band nucleus of
      Broca and in the hypothalamus, whereas additional cells were identified in the
      anterior olfactory nucleus, lateral and dorsal cortices, dorsal ventricular
      ridge, and the intergeniculate leaflet formation. Notable differences are the
      presence of NPFF-ir cells in the medial cortex and striatum of Pseudemys, which
      are lacking in Gekko. On the other hand, no NPFF-ir cells could be detected in
      the septal region and dorsal horn of the spinal cord in Pseudemys. Double
      staining with NPFF and TH antibodies revealed an intimate relationship between
      NPFF-ir and TH-ir structures but colocalization could not be established. In
      conclusion, the distribution of NPFF in the brain of Pseudemys has corroborated
      previous results in Gekko, but also revealed some notable species differences.

PMID- 18331882
TI  - Distribution of adrenomedullin-like immunoreactivity in the brain of the adult
      sea lamprey.
AB  - Adrenomedullin (AM) is a neuropeptide widely distributed in vertebrates. In jawed
      vertebrates it has been localized in distinct regions of the central nervous
      system by means of antisera against human AM because the molecule seems to be
      well conserved across species. In this study, we have analyzed the localization
      of AM-like immunoreactive (AM-ir) cell bodies and fibers throughout the brain of
      the adult sea lamprey Petromyzon marinus, by using immunohistochemistry. Several
      AM-ir cell populations were found in the basal plate of the secondary
      prosencephalon, being more numerous in the hypothalamus, as well as two in the
      diencephalon and one in the mesencephalon; in addition two cell populations were
      found in the rhombencephalic alar plate, one in the isthmic region and other in
      the nucleus of the solitary tract. Immunolabeled fibers were widespread
      throughout the lamprey brain, but were more abundant in the basal plate. Of
      particular interest was the conspicuous innervation of the striatum by AM-ir
      fibers. In addition, our results indicate that AM-ir cells and fibers are present
      in the lamprey hypothalamo-neurohypophyseal system, suggesting that AM plays some
      important role in the control of pituitary gland function.

PMID- 18331883
TI  - Identification of neural progenitor pools by E(Spl) factors in the embryonic and
      adult brain.
AB  - The maintenance of progenitor cells is a crucial aspect of central nervous system
      development and maturation, and bHLH transcription factors of the E(Spl)
      subfamily are involved in this process in all vertebrates studied to date. In the
      zebrafish embryonic neural plate, a large number of E(Spl) genes (her genes) are
      at play. We review recent data on this point, and propose a model where distinct
      subsets of these genes define different progenitor subtypes. Analysis of her
      genes expression in the adult zebrafish brain suggests that part of the embryonic
      her cascade might also be reused to define progenitors during adulthood. Further,
      available evidence on orthologous genes in the mouse (Hes genes) point to
      different modes of Hes regulation depending on cell location within the embryonic
      neural tube, perhaps associated with distinct progenitor types in this species as
      well. Out of these comparisons emerges a simple model of neural stem cell
      maintenance applicable from embryonic development until adulthood as well as
      across species. This working model suggests the directions for future
      experiments.

PMID- 18331884
TI  - Synthesis of estrogens in progenitor cells of adult fish brain: evolutive novelty
      or exaggeration of a more general mechanism implicating estrogens in
      neurogenesis?
AB  - In contrast to other vertebrates, in which the adult brain shows limited adult
      neurogenesis, teleost fishes exhibit an unparalleled capacity to generate new
      neurons as adults, suggesting that their brains present a highly permissive
      environment for the maintenance and proliferation of adult progenitors. Here, we
      examine the hypothesis that one of the factors permitting establishment of this
      favourable environment is estradiol. Indeed, recent data showed that radial glial
      cells strongly expressed one of two aromatase duplicated genes. Aromatase is the
      estrogen-synthesizing enzyme and this observation is of great interest, given
      that radial glial cells are progenitor cells capable of generating new neurons.
      Given the well-documented roles of estrogens on cell fate, and notably on cell
      proliferation, these data suggest that estradiol could be involved in maintaining
      and/or activating these progenitors. Examination of recent data in birds and
      mammals suggests that the situation in fish could well be an exaggeration of a
      more general mechanism implicating estrogens in neurogenesis. Indeed, there is
      accumulating evidence that estrogens are involved in embryonic, adult or
      reparative neurogenesis in other vertebrates, notably in mammals.

PMID- 18331885
TI  - Stage-specific effects of retinoic acid on gene expression during forebrain
      development.
AB  - Treatment of early gastrula- and neurula-staged Xenopus embryos with all-trans
      retinoic acid (RA) results in truncation of the anterior structures of the
      forebrain and head. The extent of truncation is dependent upon both the stage of
      immersion and the RA concentration used. As a method to investigate genes
      important during early forebrain regionalization, late gastrula and neurula
      embryos were immersed for 2h within low (1x10(-9)M to 5x10(-8)M) concentrations
      of RA. Embryos were allowed to develop to tadpole stages and forebrain marker
      genes were assessed for any alteration in patterns of expression. Comparisons of
      controls to experimental groups indicated that the greatest sensitivity to low
      levels of RA occurred just before the initial expression of the forebrain
      specific markers investigated. We concluded that forebrain regionalization and
      gene expression occurred in the following order: Xotx2-->Xsix3-->Xrx (&Xfez1)-
      >Xbf1-->Xemx1. Xsix3 seems to be very important for the initial parcellation of
      telencephalon, retinal and diencephalon areas.

PMID- 18331886
TI  - The particles of the embryonic cerebrospinal fluid: how could they influence
      brain development?
AB  - During brain development, the embryonic cerebrospinal fluid (E-CSF) allows brain
      expansion and promotes neuroepithelial cell survival, proliferation or
      differentiation. Previous analyses of E-CSF content have revealed a high protein
      concentration and the presence of membranous particles. The role of these
      particles in the E-CSF remains poorly investigated. In this study we showed that
      the E-CSF contains at least two pools of particles: lipoproteins and exosome-like
      particles. We showed that these two populations of particles strongly interact
      with neuropithelial cells via an endocytic process, which display regional
      specificity along the developing neural tube. Finally, we explore and discuss the
      possibility that these interactions may influence brain development through the
      regulation of morphogen and growth factor signaling transduction.

PMID- 18331887
TI  - Early pretectal gene expression pattern shows a conserved anteroposterior
      tripartition in mouse and chicken.
AB  - A changing network of gene activity settles the molecular basis of
      regionalization in the nervous system. As a consequence, analysis of combined
      gene expressions patterns represents a powerful initial approach to decode the
      complex process that drives neurohistogenesis and generates distinct
      morphological features. We have started to do a comparative screening of
      molecular regionalization in the mouse and chicken pretectal region at selected
      developmental stages. The pretectal region is composed of alar and roof plate
      derivatives of prosomere 1. This is a poorly understood region, best
      characterized in avian embryos and adults because nuclear cytoarchitectonic
      delimitation is clearer in these animals. During the early regionalization
      process the main pretectal boundaries and histogenetic/progenitor domains are
      established. We explore here Pax3, Pax6 and Six3 mRNA expression (and PAX3
      immunoreactivity) in both chicken and mice, with the aim to compare their
      respective patterns. Our focus is centered on stages HH22-HH24 in chicken and
      embryonic days E11.5-E12.5 in mice. We found that, in both vertebrates, the same
      three main anteroposterior subdivisions are distinguished by these markers. They
      were defined as precommissural, juxtacommissural and commissural pretectal
      domains. These preliminary data represent an initial scaffold to explore more
      detailed pretectal regionalization processes and provide an important new key to
      approach unresolved pretectal homologies between vertebrates.

PMID- 18331888
TI  - Expression of cLhx6 and cLhx7/8 suggests a pallido-pedunculo-preoptic origin for
      the lateral and medial parts of the avian bed nucleus of the stria terminalis.
AB  - We investigated the origin of the avian bed nucleus of the stria terminalis (BST)
      and other parts of the avian subpallial amygdala, by studying the expression of
      the LIM-homeobox chick genes Lhx6 (cLhx6) and Lhx7/8 (cLhx7/8) in the embryonic
      chicken telencephalon. Our results indicate that these genes are expressed in a
      subpallial subdomain partially overlapping the expression of Nkx2.1, which
      includes pallidal, peduncular, commissural preoptic and pallidoseptal
      subdivisions comparable to those of mammals. The lateral and medial parts of the
      avian BST express cLhx6 and/or cLhx7/8, suggesting that they derive from the
      Nkx2.1-expressing subpallial domain. Our results indicate that the avian lateral
      BST (BSTL) contains two components, a dorsal part rich in cLhx6 and lacking
      cLhx7/8 expression that may derive from the pallidal subdivision, and a ventral
      part showing moderate or light expression of cLhx6 and cLhx7/8, which may derive
      from the peduncular subdivision. Moreover, the medial BST (BSTM1 and BSTM2) shows
      moderate to strong expression of cLhx6 and very strong expression of cLhx7/8
      throughout development, and appears to derive from both the peduncular and the
      commissural preoptic subdivisions. Based on this, the avian dorsal BSTL appears
      comparable to the mammalian BSTL, whereas the avian ventral BSTL and at least
      part of BSTM may be comparable to the anterior and posteromedial parts of the
      mammalian BSTM. We also identified a ventrolateral portion of BSTM (BSTM3) and
      other cell corridors expressing cLhx6 and/or cLhx7/8 in chicken and propose their
      homology with specific parts of the extended amygdala of mammals.

PMID- 18331889
TI  - Implication of the Drosophila beta-amyloid peptide binding-like protein AMX in
      Notch signaling during early neurogenesis.
AB  - Lateral inhibition provides a mechanism to regulate neuroblast specification
      during early neurogenesis in Drososphila melanogaster embryos. This mechanism is
      mediated by the highly conserved Notch pathway. Defective lateral inhibition
      results in CNS hyperplasia at the expense of ectoderm development, hence genes
      causing this defect are called neurogenic. D. melanogaster almondex (amx) is a
      maternal neurogenic gene, crucially required for embryonic lateral inhibition.
      Genetic interaction studies previously revealed amx as a positive Notch pathway
      partner in several processes, acting potentially upstream of Notch. We show here
      that embryonic overexpression of Notch intracellular domain partially rescues
      maternal lack of amx, suggesting a role for AMX at the level of Notch processing.
      Our molecular data reveal that amx is ubiquitously expressed and encodes a
      conserved putative transmembrane protein, composed of several domains that are
      differently required for amx function in the fly. Sequence comparisons identify
      AMX as a Drosophila Beta-amyloid peptide Binding Protein (BBP) family member, a
      BBP-like protein or dBLP. Based on these data, we discuss the potential molecular
      function of AMX in early neurogenesis.

PMID- 18331890
TI  - Quantitative analysis of neural plate thickness and cell density during
      gastrulation in the chick embryo.
AB  - We quantitatively analyzed the developing prospective neural and non-neural
      ectoderm during chicken gastrulation on semithin transverse sections. At stage
      PS8 (primitive streak stage 8 of Lopez-Sanchez et al. [C. Lopez-Sanchez, L.
      Puelles, V. Garcia-Martinez, L. Rodriguez-Gallardo, Morphological and molecular
      analysis of the early developing chick requires an expanded series of primitive
      streak stages, J. Morphol. 264 (2005) 105-116.], equivalent to stage HH4), the
      thickest area of the ectoderm agrees in extent with the fate-mapped neural plate
      we had reported previously. The thickness of the median ectoderm is constantly
      higher up to a distance of 250mum from Hensen's node, and thickness decreases
      along a mediolateral gradient with a further drop at the prospective lateral
      border of the neural plate. A higher cell density of the developing ectoderm also
      coincided with the prospective neural plate. We observed that cell death does not
      play an important role in the spatial definition of the neural plate.

PMID- 18331891
TI  - The brain in the early fossil jawless vertebrates: evolutionary information from
      an empty nutshell.
AB  - Various 535-365 million year-old extinct jawless vertebrates taxa provide either
      direct or indirect information about brain and cranial nerve morphology. The
      paraphyletic group referred to as "ostracoderms", includes some forms in which
      the braincase closely encapsulated the brain, thereby providing relatively
      accurate data about its overall external morphology. Current morphology-based
      phylogenies suggests that "ostracoderms" are in fact jawless stem gnathostomes,
      and the closely similar aspect of their brain cavity suggests that it illustrates
      the ancestral condition of the gnathostome brain and fills the morphological gap
      between the brain condition of the extant cyclostomes and that of the extant
      jawed vertebrates.

PMID- 18331892
TI  - Basic features of the ancestral chordate brain: a protochordate perspective.
AB  - Basic features of the anterior nerve cord in amphioxus larvae are summarized to
      highlight its essential similarity with the vertebrate brain. Except for a pineal
      homolog, the amphioxus brain consists of a much simplified version of the ventral
      brainstem, including a region probably homologous with the hypothalamus, and a
      locomotory control center roughly comparable to the vertebrate tegmentum and
      reticulospinal system. Amphioxus has direct pathways for activating its
      locomotory circuits in response to mechanical stimuli via epithelial sensory
      cells, but this response is evidently modulated by inputs from diverse sensory
      type cells located in the putative hypothalamic homolog, and from the lamellar
      body, the pineal homolog. This implies that a basic function of the amphioxus
      brain is to switch between locomotory activities, of which there are several, and
      the principal non-locomotory one, namely feeding. A similar involvement in
      switching between behavioral modes may thus have been a core brain function in
      ancestral chordates. Currently, however, incomplete knowledge of the physiology
      and behavior of amphioxus limits how effectively it can be used as an
      evolutionary model. Eye evolution is briefly discussed to illustrate how a better
      understanding of living forms can inform the evolutionary debate. An account of
      recent data on dorsoventral inversion is also included, as this bears directly on
      the question of where the chordate brain originated in relation to other
      structures. It now appears likely that key components of the ancestral brain were
      originally located around the mouth. A secondary repositioning of the latter
      would therefore have been required before a unitary brain could be assembled and
      internalized. This association between the mouth and the evolving brain
      reinforces the idea of a fundamental early connection between core brain
      structures and the control of feeding activity.

PMID- 18331893
TI  - Expression of the amphioxus Pit-1 gene (AmphiPOU1F1/Pit-1) exclusively in the
      developing preoral organ, a putative homolog of the vertebrate adenohypophysis.
AB  - For the Florida amphioxus (Branchiostoma floridae), the full-length sequence and
      developmental expression of AmphiPOU1F1/Pit-1 are described. This gene, which is
      present in a single copy in the genome, is homologous to Pit-1 genes of
      vertebrates that play key roles in the development of the adenohypophysis. During
      amphioxus development, AmphiPOU1F1/Pit-1 transcripts are limited to Hatschek's
      left diverticulum and the larval tissue developing from it--namely the concave
      portion of the preoral organ. No other expression domains for this gene were
      detected during embryonic and larval development. From data currently available
      for hemichordates, amphioxus and ascidians, the best supported homologs for the
      vertebrate adenohypophysis are the preoral ciliary organ of hemichordates,
      preoral organ/Hatschek's pit of amphioxus and the neural gland/duct complex of
      ascidians. Better insights into pituitary evolution will require additional
      information: for invertebrate deuterostomes, more of the key pituitary genes in
      hemichordates and tunicates need to be studied; for the more basal groups
      vertebrates, it will be important to determine whether the source of the
      adenohypophysis is endodermal or ectodermal and to demonstrate what, if any,
      contribution mesodermal head coeloms might make to the developing pituitary.

PMID- 18331894
TI  - Does hair cell differentiation predate the vertebrate appearance?
AB  - It is generally accepted that the three main chordate groups (tunicates,
      cephalochordates and vertebrates) originated from a common ancestor having the
      basic features of the chordate body plan, i.e. a neural tube and a notochord
      flanked by striated musculature. There is now increasing evidence that tunicates,
      rather than cephalochordates, are the vertebrate sister-group. Correlated with
      this, tunicates have sensory structures similar to those derived from placodes or
      neural crest in vertebrates. In this context, we discuss here whether the
      precursors of vertebrate hair cells, which are placodal in origin, were present
      in ancestral chordates. The ascidian tunicates possess a coronal organ,
      consisting of a row of mechanosensory cells that runs around the base of the oral
      siphon. Its function is to monitor the incoming water flow. The cells are
      secondary sensory cells, i.e. they lack axons and synapse with neurons whose
      somata lie in the cerebral ganglion. They are accompanied by supporting cells
      and, as in vertebrates, have varying morphologies in the species so far examined:
      in one order (Enterogona), they are multiciliate; in the other (Pleurogona), they
      may possess an apical apparatus, consisting of one or two cilia accompanied by
      stereovilli, that are graded in length. Coronal cells thus resemble vertebrate
      hair cells closely in their morphology, embryonic origin and arrangement, which
      suggests they originated early in ancestral chordates. We are continuing our
      study of the coronal organ in other ascidian species, and report new data here on
      Botrylloides leachi, which conforms with the pattern of Pleurogona and, in
      particular, with previously published results on other botryllid ascidians.

PMID- 18331895
TI  - The role of Pax genes in eye evolution.
AB  - Anatomically widely different designs of animal eyes have long been thought to
      arise independently multiple times during evolution. This morphology-based view
      has been challenged by the identification of a highly conserved transcription
      factor Pax6 that plays a key role in eye development in both flies and mammals.
      The origin of Pax genes predates the origin of eyes and the nervous system since
      a PaxB-like gene, belonging to the Pax2/5/8 gene subfamily, was identified in
      sponge lacking nervous system. Structurally similar PaxB gene is implicated in
      visual system development in jellyfish, the most basal organism possessing
      complex eyes. The widespread use of Pax genes in the genetic program underlying
      eye formation throughout the animal kingdom raises a question why certain
      transcription factors have been frequently redeployed to build eyes. A model is
      proposed that provides a plausible explanation for the apparently ancient role of
      Pax genes in eye evolution.

PMID- 18331896
TI  - Developing a sense of scents: plasticity in olfactory placode formation.
AB  - The sense organs of the vertebrate head arise predominantly from sensory
      placodes. The sensory placodes have traditionally been grouped as structures that
      share common developmental and evolutionary characteristics. In attempts to build
      a coherent model for development of all placodes, the fascinating differences
      that make placodes unique are often overlooked. Here I review olfactory placode
      development with special attention to the origin and cell movements that generate
      the olfactory placode, the derivatives of this sensory placode, and the degree to
      which it shows plasticity during development. Next, through comparison with
      adenohypophyseal, and lens placodes I suggest we revise our thinking and
      terminology for these anterior placodes, specifically by: (1) referring to the
      peripheral olfactory sensory system as neural ectoderm because it expresses the
      same series of genes involved in neural differentiation and differentiates in
      tandem with the olfactory bulb, and (2) grouping the anterior placodes with their
      corresponding central nervous system structures and emphasizing patterning
      mechanisms shared between placodes and these targets. Sensory systems did not
      arise independent of the central nervous system; they are part of a functional
      unit composed of peripheral sensory structures and their targets. By expanding
      our analyses of sensory system development to also include cell movements, gene
      expression and morphological changes observed in this functional unit, we will
      better understand the evolution of sensory structures.

PMID- 18331897
TI  - Calcium-binding proteins label functional streams of the visual system in a
      songbird.
AB  - The vertebrate nervous system has been shown to contain high concentrations of
      intracellular calcium-binding proteins, each of them with a restricted expression
      pattern in specific brain regions and specific neuronal subpopulations. Using
      immunohistochemical staining techniques, we analyzed the expression pattern of
      calbindin, calretinin and parvalbumin in visual brain areas of a songbird
      species, the zebra finch (Taeniopyga guttata). Here we show that the analyzed
      proteins are expressed in a complementary fashion within different brain
      substructures generally corresponding to functional subpathways of the avian
      visual system. In detail, calbindin is expressed in the brain structures that
      belong to the thalamofugal pathway, whereas parvalbumin-positive neurons are
      found in the brain structures that are part of the tectofugal visual pathway.
      Originally, the expression of calcium-binding proteins has been associated with
      specific morphological or neurochemical criteria of neurons. Our results suggest
      that their expression pattern also indicates a functional segregation of brain
      substructures linked to vision in the zebra finch brain. As the selective
      labeling of functional streams has also been shown for the visual system in
      mammalian species, function-selective expression of calcium-binding proteins
      might be a general feature of vertebrates.

PMID- 18331898
TI  - The visual system in subterranean African mole-rats (Rodentia, Bathyergidae):
      retina, subcortical visual nuclei and primary visual cortex.
AB  - We have studied the visual system of subterranean mole-rats of the rodent family
      Bathyergidae, for which light and vision seem of little importance. The eye
      diameter varies between 3.5mm in Bathyergus suillus and 1.3mm in Heterocephalus
      glaber. The small superficial eyes have features typical of sighted animals
      (clear optics, well-developed pupil and well-organized retina) and appear suited
      for proper image formation. The retinae are rod-dominated but possess rather high
      cone proportions of about 10%. The total number of retinal ganglion cells and
      optic nerve fibres ranges between 6000 in Bathyergus suillus and 2100 in
      Heliophobius argenteocinereus. Visual acuity (estimated from counts of peak
      ganglion cell density and axial length of the eye) is low, ranging between 0.3
      and 0.5 cycles/degree. The retina projects to all the visual structures described
      in surface-dwelling sighted rodents. The suprachiasmatic nucleus is large and
      receives bilateral retinal input. All other visual nuclei are reduced in size and
      receive almost exclusively contralateral retinal projections of varying
      magnitude. The primary visual cortex is small and, in comparison to other
      rodents, displaced laterally. In conclusion, the African mole-rats possess
      relatively well-developed functional visual subsystems involved in
      photoperiodicity, form and brightness discrimination. In contrast, visual
      subsystems involved in coordination of visuomotor reflexes are severely reduced.
      This pattern suggests the retention of basic visual capabilities. Residual vision
      may enable subterranean mammals to localize breaches in the burrows that let in
      light thus providing a cue to enable mole-rats to reseal such entry points and to
      prevent entry of predators.

PMID- 18331899
TI  - Evolution of a sensory novelty: tympanic ears and the associated neural
      processing.
AB  - Tympanic hearing is a true evolutionary novelty that appears to have developed
      independently in at least five major tetrapod groups-the anurans, turtles,
      lepidosaurs, archosaurs and mammals. The emergence of a tympanic ear would have
      increased the frequency range and sensitivity of hearing. Furthermore, tympana
      were acoustically coupled through the mouth cavity and therefore inherently
      directional in a certain frequency range, acting as pressure difference
      receivers. In some lizard species, this acoustical coupling generates a 50-fold
      directional difference, usually at relatively high frequencies (2-4kHz). In
      ancestral atympanate tetrapods, we hypothesize that low-frequency sound may have
      been processed by non-tympanic mechanisms like those in extant amphibians. The
      subsequent emergence of tympanic hearing would have led to changes in the central
      auditory processing of both high-frequency sound and directional hearing. These
      changes should reflect the independent origin of the tympanic ears in the major
      tetrapod groups. The processing of low-frequency sound, however, may have been
      more conserved, since the acoustical coupling of the ancestral tympanate ear
      probably produced little sensitivity and directionality at low frequencies.
      Therefore, tetrapod auditory processing may originally have been organized into
      low- and high-frequency streams, where only the high-frequency processing was
      mediated by tympanic input. The closure of the middle ear cavity in mammals and
      some birds is a derived condition, and may have profoundly changed the operation
      of the ear by decoupling the tympana, improving the low-frequency response of the
      tympanum, and leading to a requirement for additional neural computation of
      directionality in the central nervous system. We propose that these
      specializations transformed the low- and high-frequency streams into time and
      intensity pathways, respectively.

PMID- 18331900
TI  - Vestibulotrigeminal pathways in the frog, Rana esculenta.
AB  - The aim of this study was to investigate whether primary vestibular afferent
      fibers establish direct connections with the motor and sensory trigeminal system
      in the brainstem of the frog. The experiments were carried out on Rana esculenta.
      In anaesthetized animals the trigeminal and vestibular nerves were prepared, and
      their proximal stumps were labeled either with fluorescein binding dextran amine
      (trigeminal nerve) or tetramethylrhodamine dextran amine (vestibulocochlear
      nerve). With a confocal laser scanning microscope we could detect close
      connections between the vestibular fibers and branches of the dorsal dendritic
      array of the jaw-closing motoneurons, suggestive of monosynaptic contacts. In the
      other parts of the brainstem, vestibular terminals were detected in the
      termination areas of the mesencephalic trigeminal nucleus and of the Gasserian
      (Vth) ganglion and they were probably involved in polysynaptic connections. In
      agreement with the results obtained in mammalian species, the present findings
      suggest that the vestibulotrigeminal relationship is quite complex and uses
      multiple pathways to connect the vestibular apparatus with the motor and sensory
      nuclei of the trigeminal nerve in the anurans as well.

PMID- 18331901
TI  - Immunocytochemical study of calretinin and calbindin D-28K expression in the
      retina of three cartilaginous fishes and a cladistian (Polypterus).
AB  - The distribution of two calcium-binding proteins, calbindin D-28K (CB) and
      calretinin (CR) was studied in the retina of a cladistian, Polypterus senegalus,
      and three cartilaginous fishes (Scyliorhinus canicula, Raja undulata and Torpedo
      marmorata). Western blot analysis of brain extracts revealed the lack of cross
      reactivity of the used antibodies. In Polypterus, CB and CR immunoreactivities
      were observed in some amacrine and ganglion cells, but scarce cells showed CR/CB
      colocalization. Furthermore, CR immunoreactivity was present in a number of
      displaced bipolar cells and in some putative displaced ganglion cells, whereas CB
      immunoreactivity was found in some cones. No positive retinal structure was
      observed with the CB antibody used in cartilaginous fishes. Instead, CR was
      expressed in some amacrine, horizontal and ganglion cells of the dogfish and
      skate and, in some ganglion cells of the electric ray. The comparative analysis
      suggests, (1) the presence of CB-positive photoreceptor cells in the retina of
      cladistians seems to be apomorphic (in jawed fishes) in contrast with the
      plesiomorphic condition of this character in land vertebrates; (2) the presence
      of CR in amacrine and ganglion cells is a conserved feature along vertebrate
      phylogeny, whereas its variable expression in bipolar and horizontal cells
      represents a derived character; (3) the absence of CB in horizontal cells in
      cladistians could represent a derived character; and (4) the presence of CR
      displaced bipolar and putative displaced ganglion cells in Polypterus is shared
      with basal groups of actinopterygians.

PMID- 18331902
TI  - Calbindin-D28k and calretinin as markers of retinal neurons in the anuran
      amphibian Rana perezi.
AB  - In the present study we have analyzed the distribution of the calcium binding
      proteins calbindin-D28k (CB) and calretinin (CR) immunoreactive cells in the
      retina of the anuran Rana perezi using poly- and mono-clonal antibodies that were
      proven to be specific in the amphibian brain, without cross-reactivity. Double
      immunohistofluorescence techniques were used to demonstrate colocalization of
      both proteins in the same retinal cells. In addition, retrograde tracing
      experiments from the optic nerve were conducted to labeled ganglion cells and
      these were observed in combination with CB and/or CR immunohistochemistry. Cells
      containing CB were identified as all cones, scattered bipolar and amacrine cells
      together with cells in the ganglion cell layer. The pattern of CR
      immunoreactivity was strikingly different. Abundant cells contained CR in the
      inner retinal layers including horizontal, bipolar and amacrine cells, and cells
      in the ganglion cell layer. By means of double immunohistochemistry it was found
      that only subpopulations of amacrine cells and cells in the ganglion cell layer
      contained both CB and CR. Tracing from the optic nerve revealed retrogradely
      labeled ganglion cells with different morphologies and most of them contained CB
      and/or CR. All these data taken together suggest that in amphibians CB and CR are
      distinctly and precisely distributed in retinal neurons showing, however,
      peculiar features not observed previously in other vertebrates.

PMID- 18331903
TI  - The evolution of the complex sensory and motor systems of the human brain.
AB  - Inferences about how the complex sensory and motor systems of the human brain
      evolved are based on the results of comparative studies of brain organization
      across a range of mammalian species, and evidence from the endocasts of fossil
      skulls of key extinct species. The endocasts of the skulls of early mammals
      indicate that they had small brains with little neocortex. Evidence from
      comparative studies of cortical organization from small-brained mammals of the
      six major branches of mammalian evolution supports the conclusion that the small
      neocortex of early mammals was divided into roughly 20-25 cortical areas,
      including primary and secondary sensory fields. In early primates, vision was the
      dominant sense, and cortical areas associated with vision in temporal and
      occipital cortex underwent a significant expansion. Comparative studies indicate
      that early primates had 10 or more visual areas, and somatosensory areas with
      expanded representations of the forepaw. Posterior parietal cortex was also
      expanded, with a caudal half dominated by visual inputs, and a rostral half
      dominated by somatosensory inputs with outputs to an array of seven or more motor
      and visuomotor areas of the frontal lobe. Somatosensory areas and posterior
      parietal cortex became further differentiated in early anthropoid primates. As
      larger brains evolved in early apes and in our hominin ancestors, the number of
      cortical areas increased to reach an estimated 200 or so in present day humans,
      and hemispheric specializations emerged. The large human brain grew primarily by
      increasing neuron number rather than increasing average neuron size.

PMID- 18331904
TI  - Genetic and epigenetic contributions to the cortical phenotype in mammals.
AB  - One aspect of cortical organization, cortical field size, is variable both within
      and across species. The observed variability arises from a variety of sources,
      including genes intrinsic to the neocortex and a number of extrinsic and
      epigenetic factors. Genes intrinsic to the cortex are directly involved in the
      development and specification of cortical fields and are regulated from both
      signaling centers located outside of the neocortex, which secrete diffusible
      molecules, and the expression of transcription factors within the neocortex. In
      addition, extrinsic factors such as the type, location and density of sensory
      receptor arrays and how these receptor arrays are utilized, are also strongly
      related to cortical field size. Epigenetic factors including the relative
      activity patterns generated by the different types of physical stimuli in a given
      environment also contribute to differences in cortical organization, including
      cortical field size. Since both genetic and epigenetic factors contribute to
      cortical organization, some aspects of the cortical phenotype evolve, while other
      aspects of the cortical phenotype persist only if the environment in which an
      individual develops is relatively stable.

PMID- 18331905
TI  - Evolution of cortical neurogenesis.
AB  - The neurons of the mammalian neocortex are organised into six layers. By
      contrast, the reptilian and avian dorsal cortices only have three layers which
      are thought to be equivalent to layers I, V and VI of mammals. Increased
      repertoire of mammalian higher cognitive functions is likely a result of an
      expanded cortical surface area. The majority of cortical cell proliferation in
      mammals occurs in the ventricular zone (VZ) and subventricular zone (SVZ), with a
      small number of scattered divisions outside the germinal zone. Comparative
      developmental studies suggest that the appearance of SVZ coincides with the
      laminar expansion of the cortex to six layers, as well as the tangential
      expansion of the cortical sheet seen within mammals. In spite of great variation
      and further compartmentalisation in the mitotic compartments, the number of
      neurons in an arbitrary cortical column appears to be remarkably constant within
      mammals. The current challenge is to understand how the emergence and elaboration
      of the SVZ has contributed to increased cortical cell diversity, tangential
      expansion and gyrus formation of the mammalian neocortex. This review discusses
      neurogenic processes that are believed to underlie these major changes in
      cortical dimensions in vertebrates.

PMID- 18331906
TI  - Tangentially migrating GABAergic cells of subpallial origin invade massively the
      pallium in developing sharks.
AB  - We studied the development of the GABAergic system in the telencephalon of the
      dogfish Scyliorhinus canicula using GABA and glutamate decarboxylase (GAD)
      immunocytochemistry. The earliest GABA-expressing cells appeared in the basal
      telencephalon (subpallium) of stage 24 embryos. Shortly after, the subpallium
      showed abundant GABA-expressing neuroblasts near the meningeal surface or
      migrating radially in the neuroepithelium. The limit between the GABA-expressing
      region and the remainder of the telencephalon (pallium) was sharp and coincides
      with the pallial/subpallial boundary. At stage 28, GABA-expressing cells with the
      morphology of tangentially migrating cells (showing a thick growth cone-like
      leading process) migrate from a dome-shaped protrusion of the lateral subpallium
      and extended laterally and rostrodorsally into the pallium following either a
      superficial route or coursing periventricularly. At later stages, abundant GABA
      expressing cells were seen in various pallial regions and strings of GABA
      expressing cells, possibly migrating, were also noted. The colonization of the
      dogfish pallium by GABA-expressing cells, originating from the subpallium, is
      strongly reminiscent of the palliopetal tangential migrations of GABA-expressing
      cells demonstrated in the telencephalon of mammals and follows similar routes.
      These results strongly suggest that tangential migrations of GABA-expressing
      cells appeared very early in vertebrate forebrain evolution.

PMID- 18331907
TI  - Development and adult organization of the lateral part of the bed nucleus of the
      stria terminalis in the chicken.
AB  - The lateral part of the bed nucleus of the stria terminalis (BSTL) is a component
      of the subpallial amygdala located near the ventral sulcus of the lateral
      ventricle, but its limits have not been well defined in birds. In this study, we
      analyzed the expression patterns of a number of neurochemical markers: GABA,
      calbindin (CB), calretinin (CR), or neuronal nitric oxide synthase (nNOS), in the
      embryonic and adult chicken brain, to further characterize the organization of
      the avian BSTL. From embryonic day 16, it was possible to distinguish three
      different regions within BSTL on the basis of cytoarchitectonic and
      immunohistochemical features. A central region, referred to as lateral bed
      nucleus of the stria terminalis pars densocellularis (BSTLdc), is characterized
      by numerous tightly packed cell bodies, most of which are GABA-immunoreactive
      (ir), and two peripheral regions with lower cellular density displaying a
      moderate GABA expression, referred to as lateral bed nucleus of the stria
      terminalis, plexiform part 1 (BSTLp1) and plexiform part 2 (BSTLp2),
      respectively. In contrast to BSTLdc, both plexiform parts are characterized by
      the presence of many fibers and terminals immunoreactive for nNOS and CR, as well
      as some CR-ir scattered cells. A distinctive feature of BSTLp2 is a population of
      CB-ir cells embedded in a slightly CB-ir neuropil. Comparison of our
      immunohistochemical data with gene expression data suggests that BSTLdc and
      BSTLp1 are pallidal in nature, whereas BSTLp2 receives important contributions
      from the entopeduncular/preoptic area.

PMID- 18331908
TI  - Hyaluronan accumulates around differentiating neurons in spinal cord of chicken
      embryos.
AB  - One major component of the extracellular matrix is hyaluronan (HA) which is
      thought to play a crucial role in the development of different organs including
      the central nervous system (CNS). HA is bound by specific receptors, CD44 and
      RHAMM, depending on cell types of CNS. However, data are lacking on the relation
      of HA to different cell populations in developing CNS. To provide new data about
      the co-localization of HA with the various cellular structures of the developing
      spinal cord, we studied the distribution pattern of hyaluronan in chicken embryos
      at Hamburger-Hamilton (HH) stages 8-39. A biotinylated HA-binding complex was
      used in combination with immunohistochemistry for proliferating and
      differentiating neurons. The intensity of the HA signal was determined by digital
      densitometry from histological sections. We found three mediolaterally oriented
      layers in the HA distribution pattern in stage HH23: (1) a moderate HA signal was
      detected in the ventricular zone; (2) strong HA accumulation was measured around
      Lim1,2-expressing cells (differentiating neurons) and early MNR2-expressing
      neurons (early motoneurons), corresponding to the intermediate zone; (3) a strong
      pericellular HA reaction was found around the neurons of the marginal zone.
      Interestingly, the peripheral nerves did not show HA signals. These findings
      suggest a crucial role of HA during neuronal development. We propose that HA may
      be involved in cell migration and axonal growth in the developing spinal cord.

PMID- 18331909
TI  - Dendrodendritic and dendrosomatic contacts between oculomotor and trochlear
      motoneurons of the frog, Rana esculenta.
AB  - Gaze fixation requires very fast movements of the eye during body displacement.
      The morphological and physiological background of the very fine and continuous
      tuning of gaze fixation is not yet fully understood. In a previous study we have
      shown that the dendrites of oculomotor neurons form bundles which invade the
      trochlear nucleus, and vice versa, trochlear dendritic bundles invade the
      oculomotor nucleus. Earlier physiological observations demonstrating electrotonic
      coupling between dendrites of spinal motoneurons in the frog suggest a similar
      mechanism between the oculomotor and trochlear motoneurons. We studied a possible
      morphological basis of gaze fixation. The experiments were carried out on common
      water frogs, Rana esculenta. The trochlear and oculomotor nerves were cut, and
      their proximal stumps were labeled simultaneously with different retrograde
      fluorescent tracers. Using confocal laser scanning microscope we detected a large
      number of close contacts in both nuclei, the majority of them were
      dendrodendritic apposition. The distance between the adjacent profiles suggested
      close membrane appositions without intercalating glial or neuronal elements. At
      the ultrastructural level, the dendrodendritic and dendrosomatic contacts did not
      show any morphological specialization; the long membrane appositions may provide
      ephaptic interactions between the neighboring profiles. This electrotonic
      coupling between the oculomotor and trochlear nerve motoneurons may promote the
      co-activation of the muscles responsible for vertical eye movements.

PMID- 18331910
TI  - Development of the diencephalic relay structures of the visual thalamofugal
      system in pigeons.
AB  - To compare the developmental pattern of the visual tecto- and thalamofugal
      pathways in the altricial pigeon, we examined the posthatch differentiation of
      the retinothalamic system. Choleratoxin was injected into the left and right eye
      to visualize the retinal innervation pattern of the lateral geniculate nucleus of
      the thalamus (GLd). The calcium-binding proteins parvalbumin and calbindin and
      GABA(Abeta) receptors were used as indicators for the functional development of
      the GLd. Although all retinorecipient thalamic target structures were invaded by
      retinal fibers directly after hatching, density of the projection increased
      during the first week. While the adult GLd was characterized by a substantial
      number of cells displaying calbindin-immunoreactivity and by a sparse innervation
      by parvalbumin-immunoreactive fibers, after hatching no labelling for calcium
      binding proteins could be detected. Calbindin-immunoreactivity appeared not
      before posthatching day 7, while parvalbumin-immunoreactive fibers were detected
      only after the third week. In contrast, a dense but diffuse GABA(Abeta) receptor
      labelling was present from hatching onwards that decreased during development.
      The delayed expression of calbindin as well as changes in the density of
      GABA(Abeta) receptors indicate that maturation of GLd neurons extends long into
      the posthatch period. It is likely that the GABAergic interneurons mainly develop
      within this posthatch timeframe. Combined with the delayed development of the
      parvalbumin-positive innervation, the developmental pattern of GLd neurons
      suggests that the thalamofugal networks are immature after hatching and therefore
      still sensitive to modulations of posthatch visual experience.

PMID- 18331911
TI  - Developmental changes of calretinin immunoreactivity in the lamprey spinal cord.
AB  - We studied the distribution of calretinin immunoreactivity (CR-ir) in the rostral
      and intermediate levels of the spinal cord of lampreys from embryonic to adult
      periods. CR-ir was first observed at hatching in motoneurons and primary sensory
      neurons of the spinal cord, the dorsal cells. During the prolarval period two new
      cell types showed CR-ir: ganglion cells and interneurons. Motoneurons, dorsal
      cells, and ganglion cells were strongly positive, whereas interneurons were
      weakly stained in late prolarvae. The intensity of CR-ir in these four types of
      cells changed during the larval period. Increase of CR-expression was found in
      interneurons but a decrease in dorsal cells and in ganglion cells. These changes
      were more evident in premetamorphic larvae. Postmetamorphic lampreys showed
      almost no CR-ir in dorsal cells. In adult lampreys, the interneurons showed the
      highest CR-ir, whereas motoneurons were more weakly stained than in earlier
      stages of development. Moreover, in adults the dorsal cells and the ganglion
      cells showed no CR-ir. The present study shows that CR-ir changes during lamprey
      spinal cord development in different types of neurons, sometimes in opposite
      ways. This plasticity of CR-expression may indicate different needs from subsets
      of lamprey spinal cord cells involved in the different locomotor behaviors along
      its life cycle.

PMID- 18331912
TI  - Aging of the circadian system in zebrafish and the effects of melatonin on sleep
      and cognitive performance.
AB  - Aging is a complex process involving intracellular changes and, notably,
      modifications in intercellular communications, required for coordinated responses
      to internal and external events. One of the potential reasons for such changes is
      an age-dependent failure of the integrating systems, including the circadian
      clock. Here we demonstrate that aging in a diurnal vertebrate, zebrafish (Danio
      rerio), is associated with major but selective circadian alterations. By 3-5
      years of age, zebrafish have reduced amplitude and increased fragmentation of
      entrained circadian rhythms of activity, with fast desynchronization of the
      rhythms in the absence of environmental time cues. Aging in zebrafish is also
      associated with a reduction in the overall duration of nighttime sleep, followed
      by lower activity levels and a higher arousal threshold during the day. The
      production of the principal circadian hormone, melatonin, progressively declines
      during zebrafish aging. However, the ability of melatonin to acutely promote
      sleep and entrain circadian rhythms of activity remains robust until at least 4-5
      years of age, consistent with the preserved levels of mRNA expression for
      melatonin receptors. Aged zebrafish have altered expression of the circadian
      genes zBmal1 and zPer1 but not zClock1. A lack of circadian time cues alters
      cognitive performance in aged more than in young zebrafish and this can be
      partially attenuated by daily melatonin administration. The advantages of
      zebrafish as a diurnal, small, prolific and genetically well-characterized
      vertebrate model provide new opportunities to clarify the intrinsic circadian
      factors involved in human aging and promote the search for prophylactic and
      treatment strategies.

PMID- 18331913
TI  - Evolution of brains, cognition, and consciousness.
AB  - Most current hypotheses about the neural basis for consciousness, including
      higher-level consciousness, are based on mammalian neural features, particularly
      focusing on thalamocortical circuitry. It is postulated here that since higher
      level consciousness is correlated with higher-level cognitive abilities in humans
      and other mammals, this correlation also holds for nonmammalian taxa; that the
      level of cognitive ability may be proportional to the level of consciousness; and
      that the neural basis for both is either the same or highly overlapping. Recent
      studies, ingeniously designed to be species-sensitive, have revealed a host of
      highly cognitive abilities in birds, including manifestations of working memory
      (delayed match-to-sample, episodic memory, transitive inference, and
      multistability) and category formation, language and numerical comprehension,
      tool manufacture and cultural transmission of tool design, theory of mind, and
      Piagetian object permanence to a high level. Comparisons of the neural circuitry
      reveal extensive similarity in thalamic nuclei and ascending systems to the
      pallium. However, the avian pallium lacks the laminar architecture and therefore
      cortical columns of mammals, and avian pallial projection neurons are multipolar
      rather than specifically pyramidal as in mammals. Neural features common to both
      mammals and birds, which thus may be crucially involved in the generation of both
      higher-level cognitive abilities and higher-level consciousness, include large,
      multipolar, glutamatergic neurons with extensive and densely spiny dendrites,
      with extensive interconnectedness as well as inter-regional connections,
      GABAergic inputs from local interneurons, and connections with thalamic nuclei
      that are regulated by the thalamic reticular nucleus as well as basal ganglia
      loops.

PMID- 18331914
TI  - The dolphin brain--a challenge for synthetic neurobiology.
AB  - Toothed whales (odontocetes) are a promising paradigm for neurobiology and
      evolutionary biology. The ecophysiological implications and structural
      adaptations of their brain seem to reflect the necessity of effective underwater
      hearing for echolocation (sonar), navigation, and communication. However, not all
      components of the auditory system are equally well developed. Other sensory
      systems are more or less strongly reduced such as the olfactory system and, as an
      exception among vertebrates, the vestibular system (the semicircular canals and
      vestibular nuclei). Additional outstanding features are: (1) the hypertrophy of
      the neocortex, pons, cerebellum (particularly the paraflocculus), the elliptic
      nucleus, the facial motor nucleus and the medial accessory inferior olive and (2)
      the reduction of the hippocampus. The screening of brain structures with respect
      to shared circuitry and shared size correlations resulted in central loops also
      known from other mammals which overlap in the cerebellum and serve in the
      integration and processing of sensory input. It is highly probable that for
      dolphin navigation the ascending auditory pathway, including the inferior
      colliculus and the medial geniculate body, is of utmost importance. The extended
      auditory neocortical fields project to the midbrain and rhombencephalon and may
      influence premotor and motor areas in such a way as to allow the smooth
      regulation of sound-induced and sound-controlled locomotor activity as well as
      sophisticated phonation. This sonar-guided acousticomotor system for navigation
      and vocalization in the aquatic environment may have been a major factor if not
      the key feature in the relative size increase seen in dolphin brains.

PMID- 18331915
TI  - Sexual pheromones and the evolution of the reward system of the brain: the
      chemosensory function of the amygdala.
AB  - The amygdala of all tetrapod vertebrates receives direct projections from the
      main and accessory olfactory bulbs, and the strong similarities in the
      organization of these projections suggest that they have undergone a very
      conservative evolution. However, current ideas about the function of the amygdala
      do not pay sufficient attention to its chemosensory role, but only view it as the
      core of the emotional brain. In this study, we propose that both roles of the
      amygdala are intimately linked since the amygdala is actually involved in
      mediating emotional responses to chemical signals. The amygdala is the only
      structure in the brain receiving pheromonal information directly from the
      accessory olfactory bulbs and we have shown in mice that males emit sexual
      pheromones that are innately attractive for females. In fact, sexual pheromones
      can be used as unconditioned stimuli to induce a conditioned attraction to
      previously neutral odorants as well as a conditioned place preference. Therefore,
      sexual pheromones should be regarded as natural reinforcers. Behavioural and
      pharmacological studies (reviewed here) have shown that the females' innate
      preference for sexual pheromones is not affected by lesions of the dopaminergic
      cells of the ventral tegmental area, and that the systemic administration of
      dopamine antagonists do not alter neither the attraction nor the reinforcing
      effects of these pheromones. Anatomical studies have shown that the vomeronasal
      amygdala gives rise to important projections to the olfactory tubercle and the
      islands of Calleja, suggesting that these amygdalo-striatal pathways might be
      involved in the reinforcing value of sexual pheromones.

PMID- 18331916
TI  - Vomeronasal inputs to the rodent ventral striatum.
AB  - Vertebrates sense chemical signals through the olfactory and vomeronasal systems.
      In squamate reptiles, which possess the largest vomeronasal system of all
      vertebrates, the accessory olfactory bulb projects to the nucleus sphericus,
      which in turn projects to a portion of the ventral striatum known as
      olfactostriatum. Characteristically, the olfactostriatum is innervated by
      neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this
      study, the possibility that a structure similar to the reptilian olfactostriatum
      might be present in the mammalian brain has been investigated. Injections of
      dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus
      (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and
      mice. The resulting anterograde labeling includes the olfactory tubercle, the
      islands of Calleja and sparse terminal fields in the shell of the nucleus
      accumbens and ventral pallidum. This projection has been confirmed by injections
      of retrograde tracers into the ventral striato-pallidum that render retrograde
      labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the
      distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P
      in the ventral striato-pallidum of rats, and the anterograde tracing of the
      vomeronasal amygdaloid input in the same material confirm that, similar to
      reptiles, the ventral striatum of mammals includes a specialized vomeronasal
      structure (olfactory tubercle and islands of Calleja) displaying dense
      neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations.
      The possibility that parts of the accumbens shell and/or ventral pallidum could
      be included in the mammalian olfactostriatum cannot be discarded.

PMID- 18331917
TI  - Comparative analysis of gene expressions among avian brains: a molecular approach
      to the evolution of vocal learning.
AB  - Among avian species, three families of birds (songbirds, parrots, and
      hummingbirds) learn songs. In the brain of these vocal learners, there are neural
      networks called 'song systems' that specialize in song learning and production.
      To explore the evolution of the molecular basis of vocal learning, we conducted a
      comparative analysis of gene expression in vocal learners (Bengalese finches and
      budgerigars) and non-learners (quails and pigeons). The expression of one gene is
      similar in vocal learners, but that of other genes is highly diverse. In non
      learners, by contrast, no nuclei-specific expression exists. These results
      suggest that songbirds and parrots acquired their song systems through both
      similar and different molecular mechanisms.

PMID- 18331918
TI  - Afferent and efferent connections of the mesencephalic reticular formation in
      goldfish.
AB  - The physiology of the mesencephalic reticular formation (MRF) in goldfish
      suggests its contribution to eye and body movements, but the afferent and
      efferent connections underlying such movements have not been determined.
      Therefore, we injected the bidirectional tracer biotinylated dextran amine into
      functionally identified MRF sites. We found retrogradely labelled neurons and
      anterogradely labelled boutons within nuclei of the following brain regions: (1)
      the telencephalon: a weak and reciprocal connectivity was confined to the central
      zone of area dorsalis and ventral nucleus of area ventralis; (2) the
      diencephalon: reciprocal connections were abundant in the ventral and dorsal
      thalamic nuclei; the central pretectal nucleus was also reciprocally wired with
      the MRF, but only boutons were present in the superficial pretectal nucleus; the
      preoptic and suprachiasmatic nuclei showed abundant neurons and boutons; the MRF
      was reciprocally connected with the preglomerular complex and the anterior
      tuberal nucleus; (3) the mesencephalon: neurons and boutons were abundant within
      deep tectal layers; reciprocal connections were also present within the torus
      semicircularis and the contralateral MRF; neurons were abundant within the
      nucleus isthmi; and (4) the rhombencephalon: the superior and middle parts of the
      reticular formation received strong projections from the MRF, while the
      projection to the inferior area was weaker; sparse neurons were present
      throughout the reticular formation; a reciprocal connectivity was observed with
      the sensory trigeminal nucleus; the medial and magnocellular nuclei of the
      octaval column projected to the MRF. These results support the participation of
      the MRF in the orienting response. The MRF could also be involved in other motor
      tasks triggered by visual, auditory, vestibular, or somatosensory signals.

PMID- 18331919
TI  - Grouping of artificial objects in pigeons: an inquiry into the cognitive
      architecture of an avian mind.
AB  - How does a pigeon see the world? Although pigeons are known to be adept at
      learning large numbers of figures, colors, and natural images, various
      experiments show that their visual cognitive specialization is more geared
      towards seeing colors and textures instead of shapes. They also excel in the
      analysis of local features instead of shapes that can only be differentiated by
      their outline. We therefore embarked into a detailed analysis of the relative
      weight of colors versus shapes in an object grouping task. At the same time we
      used a design that gave us information on the question of the relative importance
      of the S+ and S- in cognitive tests. Our strategy was to use the classic matching
      to sample task in which pigeons have to associate a sample with another stimulus
      (S+), which belongs to the same arbitrary group while at the same time avoiding
      choosing another stimulus (S-), which is part of another arbitrary group. Our
      results clearly reveal that color is, relative to shape, the primary cue that
      pigeons use to guide their decisions. Although they are in principle able to use
      shape information, they utilize shape as the last cognitive resort. Our data
      further reveal that pigeons guide their decisions in a matching to sample task
      primarily by focusing on the S+, although they also utilize information from the
      S-, albeit to a smaller extent. They are flexibly able to use cognitive match- or
      nonmatch-strategies depending on the presence or absence of color- or shape-cues.

PMID- 18331920
TI  - A morphological study of the nucleus subpretectalis of the pigeon.
AB  - In pigeons, the tectofugal system is functionally as well as structurally
      lateralized. So for example the right nucleus rotundus is less modulated by right
      forebrain influences than the left nucleus rotundus by the left ones. This
      functional lateralization pattern may depend on a dynamic balance between left
      and right tectal processing. Apart from inhibitory interactions at tectal level,
      suppressive influences might directly affect rotundal neurons by GABAergic input
      from a cluster of nuclei, the bed nuclei of the tecto-thalamic tract. A major
      afferent of these nuclei is the side branch of the tectorotundal projection which
      is of bilateral origin and which is involved in the regulation of ipsilateral as
      well as bilateral visual processing. Hence, an important role of the bed nuclei
      could be the interhemispheric communication and in turn the mediation of
      functional asymmetries. In a first step to unravel asymmetric influences of these
      nuclei, the present study investigated if the largest of the bed nuclei, the
      nucleus subpretectalis displays morphological asymmetries in the pigeon. We found
      that the nucleus subpretectalis in fact exhibits asymmetric cell sizes with
      larger cell bodies on the left side. This asymmetrical pattern was not present in
      dark-incubated animals indicating that cell size asymmetries within nucleus
      subpretectalis are induced by asymmetric photic stimulation during embryonic
      development.

PMID- 18331923
TI  - Are we moving in the right direction to improve Angle's classification?

PMID- 18331924
TI  - Treatment changes in Class II malocclusion.

PMID- 18331926
TI  - Prediction of prolonged pain experiences during orthodontic treatment.
AB  - INTRODUCTION: In this study, we investigated prolonged pain reactions in teenage
      orthodontic patients during a common orthodontic treatment. The aim was to
      examine factors predicting pain at the end of a follow-up week after placement of
      elastic separators. METHODS: Fifty-five patients (ages, 12-18 years) were
      included. Baseline assessments were made of perceived intensity of general and
      dental pain experiences, motivation for treatment, dental anxiety, and
      personality factors (self-esteem and temperament). Pain intensity was assessed on
      a visual analog scale, and pain medications were recorded. The patients were
      separated into pain and no-pain groups according to pain experiences at day 7.
      RESULTS: The pain group (mainly girls) had significantly higher ratings of
      treatment pain than in the non-pain group at all times measured except for the
      treatment day. Bivariate and multiple logistic regressions showed significant
      predictive power from motivation, dental anxiety, activity temperament, and
      vaccination pain. CONCLUSIONS: In this adolescent patient sample, low motivation
      for orthodontic treatment, high ratings of vaccination pain, elevated dental
      anxiety level, and low activity temperament characterized patients reporting pain
      1 week after the elastic separators were placed.

PMID- 18331927
TI  - Anchorage capacity of osseointegrated and conventional anchorage systems: a
      randomized controlled trial.
AB  - INTRODUCTION: Our aim in this investigation was to evaluate and compare
      orthodontic anchorage capacity of 4 anchorage systems during leveling/aligning
      and space closure after maxillary premolar extractions. METHODS: One hundred
      twenty patients (60 girls, 60 boys; mean age, 14.3 years; SD 1.73) were recruited
      and randomized into 4 anchorage systems: Onplant (Nobel Biocare, Gothenburg,
      Sweden), Orthosystem implant (Institut Straumann AG, Basel, Switzerland),
      headgear, and transpalatal bar. The main outcome measures were cephalometric
      analysis of maxillary first molar and incisor movement, sagittal growth changes
      of the maxilla, and treatment time. The results were also analyzed on an
      intention-to-treat basis. RESULTS: The maxillary molars were stable during the
      leveling/aligning in the Onplant, Orthosystem implant, and headgear groups, but
      the transpalatal bar group had anchorage loss (mean, 1.0 mm; P <.001). During the
      space-closure phase, the molars were still stable in the Onplant and Orthosystem
      groups, whereas the headgear and transpalatal bar groups had anchorage loss
      (means, 1.6 and 1.0 mm, respectively; P <.001). Thus, the Onplant and the
      Orthosystem implant groups had significantly higher success rates for anchorage
      than did the headgear and transpalatal bar groups. Compared with the Orthosystem
      implant, there were more technical problems with the Onplant. CONCLUSIONS: If
      maximum anchorage is required, the Orthosystem implant is the system of choice.

PMID- 18331928
TI  - Pendulum appliances with 2 anchorage designs: conventional anchorage vs bone
      anchorage.
AB  - INTRODUCTION: The aim of this retrospective study was to compare the
      dentoalveolar and skeletal effects obtained with 2 types of pendulum appliance
      with different anchorage designs: bone-anchored pendulum appliance (BAPA) and
      conventional pendulum appliance (CPA). METHODS: The sample consisted of 39
      patients (25 girls, 14 boys) with Angle Class II molar relationships. Correction
      of the molar relationship was achieved with the BAPA with palatal intermaxillary
      fixation screws for anchorage in the first group (n = 22) and with the CPA in the
      second group (n = 17). Lateral cephalograms before treatment and at the end of
      distalization were measured, and changes in the groups and the differences
      between the groups were analyzed statistically. RESULTS: The average
      distalization times were 6.8 months for the BAPA group and 5.1 months for the CPA
      group. The maxillary first molars were tipped 9.1 degrees in the BAPA group and
      5.3 degrees in the CPA group; the molars moved distally 4.8 mm in the BAPA group
      and 2.7 mm in the CPA group. Despite mesialization of the premolars and
      proclination of the incisors with the CPA, both premolars were spontaneously
      distalized, and the incisors were retruded with the BAPA. CONCLUSIONS: The amount
      of distal molar movement was similar between the BAPA and the CPA. No anchorage
      loss or spontaneous distal premolar and incisor movement, which might decrease
      total treatment time, was seen with the BAPA.

PMID- 18331929
TI  - Sliding resistance with esthetic ligatures: an in-vitro study.
AB  - INTRODUCTION: This study was developed to evaluate in vitro the properties
      related to sliding resistance of esthetic ligatures. METHODS: Frictional force of
      6 ligatures--2 conventional, 2 specially coated elastomeric, Teflon-coated
      (Dupont, Wilmington, Del) stainless steel, and stainless steel (control)
      ligatures--were studied by sliding 0.019 x 0.025-in stainless steel wire through
      the 0.22-in slot of stainless steel bracket. Elastomeric ligatures were tested
      for frictional and tensile forces under 3 experimental conditions: recent
      stretching, after 21 days of simulated stretching in artificial saliva, and a
      demineralizing/remineralizing regimen. Statistical analysis was conducted with
      ANOVA and Games-Howell tests. RESULTS: There was high correlation between
      frictional and tensile forces of elastomeric ligatures, with reduction of both
      after 21 days. The demineralizing/remineralizing regimen reduced the frictional
      forces of ligatures to the same level as the ligatures in artificial saliva.
      Teflon-coated and stainless steel ligatures showed the lowest initial frictional
      forces, but there was no difference in friction of stainless steel and post
      stretched elastomeric ligatures. CONCLUSIONS: Frictional forces generated by
      esthetic elastomeric ligatures under simulated oral environments are not stable
      and are more related to tensile force than to surface characteristics of the
      ligatures.

PMID- 18331930
TI  - To extract or not to extract: a diagnostic decision, not a marketing decision.

PMID- 18331931
TI  - A descriptive study of mandibular incisor alignment in untreated subjects.
AB  - INTRODUCTION: The development of mandibular incisor crowding appears to be a
      continuous process throughout life, but more evidence is needed to understand why
      changes occur. METHODS: In this study, we describe the longitudinal dental
      changes in untreated children (n = 15) who had records at 3 times and in an
      untreated adult group (n = 18) (parents) who had records for 2 times. The mean
      numbers of years between initial and final observations were 29.8 years for the
      children and 33.7 years for the parents. All subjects were participants in the
      original Burlington Growth Research Project at the University of Toronto. The
      following variables were measured to an accuracy of 0.01 mm: overjet, overbite,
      mandibular intercanine width, mandibular interfirst premolar width, mandibular
      intermolar width, mandibular arch length, Little's incisor irregularity index,
      mandibular anterior space analysis, and Carey's space analysis. RESULTS: There
      were no statistically significant (P >.01) differences between the sexes for the
      variables measured. Little's irregularity index continued to increase in all
      groups (P <.01), although this rate appeared to be lower in the parent group.
      Intercanine and interfirst premolar widths and arch lengths continued to decrease
      with age. CONCLUSIONS: These results underline the importance of studies showing
      that untreated dentitions change over time. Orthodontic patient education is
      imperative about retention protocols and late developmental crowding.

PMID- 18331932
TI  - Patient compliance and locus of control in orthodontic treatment: a prospective
      study.
AB  - INTRODUCTION: Increased understanding of orthodontic patients will improve
      communication between dentist and patient; this is important for an optimal
      treatment outcome. In this prospective study, we addressed the relationship
      between patient compliance and locus of control (LOC) characteristics and
      evaluated posttreatment changes in LOC profiles. METHODS: Two types of LOC
      questionnaires, the Rotter internal control scale (RICS) and the Nowicki
      Strickland external control scale (NSECS), were given to 561 patients before
      conventional orthodontic treatment. After orthodontic treatment, the same
      questionnaires were readministered, and patient compliance was evaluated by an
      orthodontist and 3 dental hygienists. LOC scores were calculated at the end of
      the examination period. The difference in LOC between the good and poor
      compliance groups, and the posttreatment changes in LOC were evaluated. RESULTS:
      There was no significant difference in RICS and NSECS profiles between the good
      and poor compliance groups. NSECS decreased significantly after orthodontic
      treatment, but there were no significant changes in RICS. CONCLUSIONS: Patient
      compliance appears to be a complex factor that cannot be predicted by LOC
      evaluation before orthodontic treatment. Patients who underwent orthodontic
      treatment showed decreased external control dispositions.

PMID- 18331933
TI  - Prediction of oral discomfort and dysfunction in lingual orthodontics: a
      preliminary report.
AB  - INTRODUCTION: The purpose of this prospective study was to examine the influence
      of malocclusion on the amount of discomfort of patients who were treated with
      Incognito lingual brackets (T.O.P. Service, Ormco, Amersfoort, the Netherlands;
      ibraces in North and South America, Lingualcare, Dallas, Tex). METHODS: Twenty
      one female patients (mean age, 24.8 years; SD 10.7) participated in the
      investigation and completed a standardized questionnaire before and the day after
      placement of the appliance. One experienced orthodontist, blinded to the results
      of the questionnaires, evaluated their initial cephalograms and casts with
      respect to the parameters SNA, SNB, and ANB angles; overjet; overbite; maxillary
      and mandibular anterior contact-point displacement; crossbite; open bite; and
      missing teeth. RESULTS: Malocclusion measured on the casts had no significant
      impact on the amount of discomfort or dysfunction reported by the patients. The
      SNA (r = -0.619, P = .003) and SNB (r = -0.615, P = .003) angles, however,
      correlated significantly with the restriction of tongue space; patients with an
      SNB angle that was smaller than 1 SD from the norm were significantly more prone
      to experience severe restriction of tongue space (P = .003). CONCLUSIONS: The SNA
      and SNB angles are predictors for the level of tongue-space restriction after
      placement of lingual brackets: the smaller the angles, the more prone the
      patients are to experience discomfort.

PMID- 18331934
TI  - Long-term outcome of surgical Class III correction as a function of age at
      surgery.
AB  - INTRODUCTION: In this study, we assessed whether the likelihood of a positive
      overjet 5 to 10 years after Class III surgery was affected by age at the surgery
      or the type of surgery and evaluated the amount and pattern of postsurgical
      growth. METHODS: Cephalometric measurements including overjet were evaluated from
      immediately postsurgery and long-term recall cephalograms of 104 patients who had
      had surgical Class III correction and at least 5-year recalls. The patients were
      classified as younger (<age 18 years for females at the surgery or 20 years for
      males) or older and by type of surgery (maxilla only vs mandibular only or 2
      jaw). For the younger patients, the timing of treatment was based largely on
      serial cephalometric radiographs that eventually showed minimal or no mandibular
      growth. RESULTS: Long-term changes in overjet and other cephalometric
      characteristics in the younger and the older patients were similar. No patients
      in the sample had negative overjet in the long term, but zero overjet (<1 mm) was
      observed in some patients in all groups. Patients who had mandibular setback at
      any age were 2.6 times more likely to have zero overjet in the long term (P =
      .003) than those with maxillary surgery alone. For the younger patients, the
      likelihood of zero overjet in the long term was not significantly different from
      patients who were treated later (P = .87), with or without mandibular surgery.
      CONCLUSIONS: The data support the use of serial cephalometric radiographs, with
      surgery deferred until little or no mandibular growth is observed, to determine
      the timing of Class III surgery in younger patients.

PMID- 18331935
TI  - Treatment and posttreatment effects of mandibular cervical headgear followed by
      fixed appliances in Class III malocclusion.
AB  - INTRODUCTION: In this cephalometric investigation, we compared the treatment and
      posttreatment effects on patients undergoing an initial phase of mandibular
      cervical headgear (MCH) therapy followed later by comprehensive edgewise therapy
      with untreated Class III controls. METHODS: The treated sample consisted of 21
      patients treated consecutively with MCH before the pubertal growth spurt (average
      age, 10 years 2 months at the beginning of treatment). At the final observation
      period (average age, 15 years 3 months), all patients were in decelerative growth
      phases as determined by the cervical vertebral maturation method. Active
      treatment and posttreatment effects were evaluated in the treated group with
      nonparametric statistical analysis for paired samples. The treated sample was
      compared with a nonparametric statistical test for independent samples with 20
      untreated Class III subjects who were matched for malocclusion, sex, and stage of
      cervical vertebral maturation to the treatment group. RESULTS AND CONCLUSIONS:
      MCH therapy followed by fixed appliances was shown to be an effective treatment
      for the correction of skeletal Class III malocclusion at postpubertal
      observation. The favorable skeletal effects consisted mainly of smaller increases
      in mandibular length and advancement with respect to the controls, with the final
      outcome of significant improvements in the sagittal skeletal (+4 mm for the Wits
      appraisal) and dental (+2.7 mm for overjet, -4.4 mm for molar relationship)
      parameters. This treatment protocol also induced significant downward rotation of
      the mandible (2.8 degrees ).

PMID- 18331936
TI  - Evaluation of temporomandibular disorders in Class III patients treated with
      mandibular cervical headgear and fixed appliances.
AB  - INTRODUCTION: Our aim in this study was to evaluate the prevalence of
      temporomandibular disorders (TMD) in Class III patients treated with mandibular
      cervical headgear (MCH) and fixed appliances. METHODS: The sample of 75 patients
      included 25 patients with no previous orthodontic treatment, 25 Class I patients
      who had undergone orthodontic treatment with fixed appliances and without
      extractions, and 25 patients with dentoskeletal Class III disharmonies treated
      with MCH and fixed appliances. The Helkimo index was used to test the prevalence
      of TMD symptoms in the 3 groups. The prevalence rates of the Helkimo index in the
      3 groups were compared with the z score on proportions. RESULTS: No statistically
      significant differences in the prevalence rates of the Helkimo index scores in
      the 3 groups were found (P = .367). Most subjects in the 3 groups had an Helkimo
      index of zero (66.7%). CONCLUSIONS: Subjects with Class III malocclusions treated
      with MCH and fixed appliances do not have greater prevalence of TMD symptoms than
      do Class I subjects treated with fixed appliances or untreated subjects.

PMID- 18331937
TI  - Condylar asymmetry in unilateral posterior crossbite patients.
AB  - INTRODUCTION: Posterior crossbite is defined as an abnormal buccolingual
      relationship between opposing posterior teeth including the canines in centric
      occlusion. The most common form of posterior crossbite is unilateral with a
      functional shift of the mandible toward the crossbite side. Lateral shift of the
      mandible in functional crossbite patients results in mandibular skeletal
      deflection to the crossbite side. Thus, the asymmetrical position of the mandible
      in these patients can result in asymmetrical condylar heights. The purpose of
      this study was to investigate condylar and ramal asymmetries in unilateral
      crossbite patients as compared with normocclusive subjects. METHODS: The study
      groups included 81 patients with unilateral posterior crossbite and a control
      group of 75 patients with normal occlusion. Condylar, ramal, and condylar-plus
      ramal asymmetry values were computed for all subjects on panoramic radiographs.
      Data were analyzed statistically with ANOVA for repeated measures and univariate
      ANOVA. RESULTS: The patients with unilateral posterior crossbite had more
      asymmetric condyles than did the controls. In addition, condylar, ramal, and
      condylar-plus-ramal heights on the crossbite side were smaller than those on the
      noncrossbite side. CONCLUSIONS: Subjects with functional unilateral posterior
      crossbite have asymmetrical condyles.

PMID- 18331938
TI  - Sagittal mandibular changes with overbite correction in subjects with different
      mandibular growth directions: late mixed-dentition treatment effects.
AB  - INTRODUCTION: This study involved the assessment of pretreatment and
      posttreatment lateral cephalograms from late mixed-dentition patients with Class
      II Division 1 and Division 2 malocclusions with mild mandibular crowding. All
      were selected before treatment began. METHODS: Combined growth and treatment
      effects were compared with changes in untreated subjects. The study was designed
      specifically to determine whether anteroposterior mandibular dentoalveolar and
      skeletal changes associated with reduction of deep incisal overbites, by using a
      particular late mixed-dentition treatment approach, are influenced by the
      direction of mandibular growth during treatment. RESULTS: In mesofacial and
      brachyfacial subjects, significantly greater forward movements were found at
      Point B after deep overbite correction than in dolichofacial subjects. This
      apparently enhanced effect compared with the untreated controls was not seen at
      pogonion. CONCLUSIONS: Clinicians should expect considerably greater forward
      movement of the mandibular dentoalveolus with normal mandibular growth after
      incisal bite opening in mesofacial and brachyfacial patients. As a consequence,
      less maxillary retraction might be necessary in growing mesofacial and
      brachyfacial Class II Division 1 and Division 2 patients than in dolichofacial
      patients. On the other hand, one should not expect enhancement of basal sagittal
      mandibular growth, regardless of the underlying vertical facial pattern.

PMID- 18331939
TI  - Phases of the dentition for the assessment of skeletal maturity: a diagnostic
      performance study.
AB  - INTRODUCTION: The aim of this study was to analyze the relationship between the
      circumpubertal phases of the dentition (early mixed, intermediate mixed, late
      mixed, early permanent) and skeletal maturity as assessed by means of the
      cervical vertebral maturation (CVM) method. METHODS: The sample of 1000 subjects
      included 250 (125 boys, 125 girls) in each of the 4 dentition phases. Individual
      skeletal maturity was determined by using the CVM method. The relationship
      between the skeletal maturity (stages in CVM) and the phases of the dentition was
      evaluated statistically by means of indicators of diagnostic test performance.
      RESULTS: Prepubertal stage 1 (CS1) was the variable diagnosed in the early mixed
      and intermediate mixed dentitions; pubertal stage 3 (CS3) was the variable
      diagnosed in the late mixed and early permanent dentitions. CONCLUSIONS: The
      early mixed dentition phase showed a strong diagnostic value for the
      identification of prepubertal skeletal maturity (CS1), whereas the intermediate
      mixed dentition phase had a low diagnostic value for the same prepubertal stage.
      Neither the late mixed dentition nor the early permanent dentition appeared to be
      a valid indicator for the onset of the pubertal growth spurt.

PMID- 18331940
TI  - Effects of Class III magnetic orthopedic forces on the craniofacial sutures of
      rhesus monkeys.
AB  - INTRODUCTION: The objectives of this study were to develop an intraoral
      intermaxillary Class III magnetic orthopedic appliance (MOA-III), to investigate
      the influence of Class III orthopedic forces on the craniofacial sutures of
      rhesus monkeys, and to elucidate the mechanism of Class III malocclusion
      orthopedic treatment. METHODS: Six male rhesus monkeys in the mixed-dentition
      stage were divided into 3 groups of 2 each: a 90-day experimental group, a 45-day
      experimental group, and a control group. Six craniofacial sutures were observed.
      The experimental monkeys received heavy forces (300 g) per side initially,
      created by opposing Nd(2)Fe(14)B magnetic units in a cast MOA-III. The control
      groups received no treatment. Before the appliances were inserted, metal implants
      were placed in each animal as bone markers for direct measurement. To determine
      the rate of bone apposition, each animal was injected with fluorescent dyes
      intravenously before and during the experimental period. Intraoral photographs,
      dental casts, and cephalometric radiographs of each animal were obtained at the
      beginning and end of the experiment. RESULTS: Distances between metal implants on
      both sides of the sutures were enlarged in the experimental groups. Cephalometric
      analysis showed that the treatment effects of MOA-III are a combination of
      skeletal and dental changes in the maxilla and the mandible. Distinct changes
      from physiologic growth remodeling were observed in some sutures but not in the
      control groups. No inflammation was noted in either experimental or control
      monkeys. CONCLUSIONS: The MOA-III can be an efficient intraoral appliance to
      treat Class III malocclusion that is caused by a deficient maxilla; heavy
      orthopedic forces (300 g per side) are safe and effective in the rhesus monkey.

PMID- 18331941
TI  - Force levels of fiber-reinforced composites and orthodontic stainless steel
      wires: a 3-point bending test.
AB  - INTRODUCTION: The purpose of this study was to evaluate the force levels of 2
      sizes (diameters, 0.6 and 1.2 mm) of fiber-reinforced composites (FRCs) (Ever
      Stick; Stick Teck Ltd, Turku, Finland) compared with orthodontic stainless steel
      wires (sections, 0.016, 0.018, 0.017 x 0.025, and 0.019 x 0.026 in) under the
      same testing conditions. METHODS: The samples were divided into 12 groups, each
      consisting of 10 specimens. Each sample was evaluated with a 3-point bending test
      on a universal testing machine. The FRC groups were light-cured by hand with a
      halogen curing unit (Optilux 501; SDS Kerr, Danbury, Conn) for 40 seconds. Groups
      1 through 6 were tested at 1-mm deflection, and groups 7 through 12 at 2-mm
      deflection. RESULTS: The results of ANOVA indicated significant differences among
      the various groups (P = .000). The post-hoc test showed that the 2-mm deflection
      groups had significantly higher load values than the 1-mm deflection groups (P =
      .000). The highest force levels were recorded with the 1.2-mm FRCs, followed by
      the 0.019 x 0.026-in stainless steel wires. No significant differences were found
      between the 0.6-mm FRCs and the 0.017 x 0.025-in wires. The lowest load values
      were reported with the 0.016-in stainless steel wires. CONCLUSIONS: The 1.2-mm
      FRCs showed higher load values than the other stainless steel wires and the FRCs,
      whereas no significant difference was found between the 0.6-mm FRCs and the 0.017
      x 0.025-in stainless steel wires. Thus, FRCs can be considered a viable esthetic
      alternative to full-size stainless steel wires to rigidly join dental segments to
      form anchorage units or units for active tooth movement.

PMID- 18331942
TI  - Duration of elastomeric separation and effect on interproximal contact point
      characteristics.
AB  - INTRODUCTION: The common protocol of a week-long duration of elastomeric
      separators to facilitate band placement usually causes discomfort. In this study,
      we examined the minimum separation time required to create an interproximal space
      >0.16 mm (band thickness), the interproximal changes over 24 hours after
      separator removal, and the mechanical characteristics of various separators.
      METHODS: Thirty subjects, ages 28.1 +/- 2.8 years, had an elastomeric separator
      placed between the mandibular second premolar and first molar (CP5-6) for 1, 4,
      12, and 24 hours. After separator removal, CP5-6 was measured for space and
      tightness of dental contact point (TDCP) changes up to 24 hours after separator
      removal. The mechanical behaviors of 6 manufacturers' separators were compared.
      RESULTS: After 12 and 24 hours of separation, all patients demonstrated space
      >0.16 mm (P <.001). A significant negative correlation (R = -0.59 to -0.63; P =
      .001) was found between baseline TDCP and the space measured at separator
      removal. A biphasic viscoelastic recovery (82%-95%) to baseline tightness level
      occurred within 24 hours. Variation between manufacturers was low (9%).
      CONCLUSIONS: Separators should be placed a day before banding. The patient should
      arrive 3 to 4 hours before the appointment for separator replacement if the
      separator is lost. Rapid recovery after separation removal implies the biological
      soundness of elastomeric separation regardless of the manufacturer used.

PMID- 18331943
TI  - Importance of pumice prophylaxis for bonding with self-etch primer.
AB  - INTRODUCTION: Self-etching primers (SEP) have simplified the orthodontic bonding
      process, but questions have arisen regarding their reliability and efficiency.
      The goal of this study was to assess the importance of a pumice prophylaxis
      before bonding in reducing bond failures. METHODS: Thirty orthodontic patients
      volunteered to participate in this prospective clinical trial. A split-mouth
      design was used; in each patient, 1 quadrant was randomly assigned to the pumice
      prophylaxis experimental group and the contralateral quadrant to the nonpumice
      group. A total of 508 teeth were bonded with SEP (Transbond Plus; 3M Unitek,
      Monrovia, Calif) and monitored for 3 months for bond failures. RESULTS: Thirty
      five failures (6.9%) were recorded, with 6 (2.4%) in the pumice group and 29
      (11.4%) in the nonpumice group. Chi-square analysis was used to compare bond
      failures as a total number between groups and also as the number of patients who
      experienced bond failures with each method. Statistically significant differences
      were found both in the total number of bond failures (P <.001) and in the number
      of patients with bond failures between groups (P <.01). A significantly lower and
      clinically acceptable bond failure rate was demonstrated with Transbond Plus SEP
      after pumice prophylaxis. CONCLUSIONS: This study produced strong evidence
      suggesting the need for pumice prophylaxis when using SEP for orthodontic
      bonding.

PMID- 18331944
TI  - Kinetics of fluoride release from and reuptake by orthodontic cements.
AB  - INTRODUCTION: The purposes of this in-vitro study were to compare the fluoride
      release profiles and the fluoride release, reuptake, and rerelease
      characteristics of orthodontic cements before and after topical fluoride
      treatment. METHODS: The orthodontic cements tested were 2 resin-modified glass
      ionomers (Vitremer [3M Dental Products, St Paul, Minn] and Fuji Ortho LC [GC
      Dental, Tokyo, Japan]), a glass ionomer (Ketac-Cem [Espe-Premier Dental Products,
      Norristown, Pa]), and a composite (Concise [3M Dental Products]). Fifteen
      specimens of each material were stored in plastic vials containing deionized
      water at 37 degrees C. Fluoride release was measured daily for the first 15 days
      and then weekly for a 57-day period. After initial elusion, specimens were
      exposed to 1.23% acidulated phosphate fluoride gel, and the fluoride release was
      monitored daily for 7 consecutive days. The fluoridation/elution procedure was
      repeated once, and the specimen surfaces were then examined with a scannning
      electron microscope. RESULTS: Kinetic release profiles of the test materials were
      deduced. All materials except Concise had similar fluoride-release profiles.
      Vitremer demonstrated the highest fluoride release, followed by Fuji Ortho LC and
      then Ketac-Cem in the time period of the study (P <.01). All glass-ionomer
      cements, but especially Fuji Ortho LC, showed enhanced uptake and release on
      repeated exposure to the topical fluoride treatment. Nevertheless, Vitremer
      showed the greatest surface degradation after refluoridation. CONCLUSIONS: All
      resin-modified and conventional glass ionomers studied exhibited the capacity for
      fluoride release and reuptake after fluoridation, but the subsequent fluoride
      release was transitory. Thus, the benefit from fluoride reuptake in these
      orthodontic cements should be balanced with the risk of weakening them after
      repeated fluoridation.

PMID- 18331945
TI  - Effect of chlorhexidine varnish application on mutans streptococci counts in
      orthodontic patients.
AB  - INTRODUCTION: Enamel demineralization occurs frequently around orthodontic
      brackets. High levels of mutans streptococci (MS) increase the risk of caries.
      The hypotheses tested in this study were that high-frequency application of 40%
      chlorhexidine varnish (40%CHX) results in lower levels of MS in plaque of
      orthodontic patients compared with low-frequency application, and that bimonthly
      application of 40%CHX results in lower levels of MS in plaque compared with 1%
      chlorhexidine/1% thymol varnish (1%CHX). METHODS: Eighty adolescent patients were
      randomly allocated to 4 treatment groups: monthly, bimonthly, and quarterly
      40%CHX application, and bimonthly application of 1%CHX. Plaque samples were
      collected monthly and processed for MS counts. Twenty patients dropped out before
      the evaluation time at 1 month. Data from the remaining 60 adolescents were
      analyzed by using linear regression models with the plaque bacterial ratio (PBRx)
      as the dependent variable. The trial was ended after 5 months because of a high
      number of dropouts. RESULTS: High-frequency application of 40%CHX did not provide
      lower mean PBRx than low-frequency application. Mean PBRx after 40%CHX
      application was lower than 1%CHX after 1 month (P = .002). This reduction was
      undiscernible 2 months after the application. CONCLUSIONS: 40%CHX application
      results in greater reduction of MS in plaque than 1%CHX a month after
      application. A follow-up study with a larger study population is warranted to
      test the first hypothesis.

PMID- 18331946
TI  - Midfacial protraction with skeletally anchored face mask therapy: a novel
      approach and preliminary results.
AB  - INTRODUCTION: The purpose of this pilot study was to investigate the effects of
      facemask treatment with a rigid skeletal anchor. METHODS: Miniplates were placed
      on the lateral nasal wall of the maxilla in 6 subjects (mean age, 11.8 +/- 1.1
      years). No dental tissue was incorporated into the anchorage system. Lateral
      cephalograms of each patient were evaluated at the beginning of treatment (T1),
      at the end of active treatment (T2), and at the end of follow-up (T3). RESULTS:
      In the horizontal plane, mean A-point movement was 4.8 +/- 2.0 mm in a mean of
      10.8 +/- 2.4 months. The infraorbital region showed significant anterior movement
      (mean, 3.3 +/- 1.1 mm) at T2. At T3, advancement of the maxilla and the
      infraorbital region was well maintained (mean follow-up time, 15.2 +/- 0.9
      months). Miniplate stability was excellent in all patients throughout treatment.
      CONCLUSIONS: Remarkable advancement in the middle face and consequent fullness in
      the soft-tissue profile can be achieved by using skeletal anchorage in
      conjunction with facemask therapy in the late mixed-dentition period.

PMID- 18331947
TI  - Evaluation of catch-up growth from orthodontic treatment and supplemental growth
      hormone therapy by using Z-scores.
AB  - Pituitary dwarfism causes short stature due to partial or complete inhibition of
      growth hormone (GH) secretion. Supplemental therapy with human GH (rhGH)
      accelerates the statural growth of patients, but there is limited information
      about its effects on craniofacial growth. This study describes the orthodontic
      treatment of 2 patients (a boy and a girl) diagnosed with pituitary dwarfism and
      treated with rhGH therapy. Growing children have different growth velocities
      depending on age and sex, and this complicates the assessment of treatment
      effects; therefore, we used the Z-score to evaluate changes in stature and
      craniofacial components. Growth in craniofacial structures and stature were both
      enhanced by rhGH therapy during orthodontic treatment.

PMID- 18331948
TI  - Correction of a Class III malocclusion with over 20 mm of space to close in the
      maxilla by using miniscrews for extra anchorage.
AB  - Unilateral closure of maxillary extraction spaces in patients with Class III
      malocclusion can be challenging. This case report describes the closure of first
      premolar and first molar extraction spaces in a patient with a Class III dental
      relationship. Two miniscrews were used for intraoral skeletal anchorage. The
      Class III dental relationship was corrected; a positive vertical overbite was
      achieved; occlusion of the canines, premolars, and molars was improved; and the
      extraction spaces were closed.

PMID- 18331949
TI  - Voice over Internet protocol for the orthodontic practice: a sensible switch from
      plain old telephone service.
AB  - Voice over Internet protocol (VoIP) is a revolutionary new technology that is
      causing a stir in the telecommunications industry and threatening the existence
      of traditional telephone service providers. Based on a simple method of
      converting analog audio signals into digital data before being transmitted over
      the Internet, VoIP has gained immense popularity among consumers. The technology
      is now regarded as an alternative to traditional telephone service for the
      orthodontic office. When the economics are considered, it is cost-effective,
      especially for a busy orthodontic practice where the call volumes both in and out
      are always high. VoIP has the potential to reduce costs, break the barriers
      between local vs long-distance calling, and make life easier for the office
      staff. However, deploying VoIP requires a cautious and thought-out process. Users
      should fully understand the risks and benefits before switching from the public
      switched telephone network. VoIP customers and service providers are vulnerable
      to many of the same impersonation-based attacks by those who attempt toll fraud,
      and identity and information theft. In this article, VoIP is introduced to
      orthodontic practitioners, who might be unfamiliar with this technology. Internet
      protocol based private branch exchange systems that are currently marketed as
      open-source technologies are also reviewed. Additionally, VoIP is compared with
      the traditional public switched telephone network technology and evaluated for
      its potential applications in an orthodontic office for both increased efficiency
      and cost savings.

PMID- 18331950
TI  - 'An adept in medicine': the Reverend Dr William Laing, nervous complaints and the
      commodification of spa water.
AB  - This essay addresses mineral water as a medical, experimental and economic
      material. It focuses on the career of the Reverend Dr William Laing (1742-1812),
      a physician and cleric who wrote two pamphlets about the water of provincial spa
      located in Peterhead, a town on the north-east coast of Scotland. I begin by
      outlining his education and I then reconstruct the medical theory that guided his
      efforts to identify tonics in the well's water. Next, I explain why Laing and
      several other local inhabitants thought themselves to be authorities on the
      palliative power of the water and I close by showing how such effects were
      commodified by local entrepreneurs. Although I concentrate primarily upon
      Peterhead Spa, this study touches upon several issues relevant to the types of
      medical theory and chemical experimentation that were being used in provincial
      Scotland during the late eighteenth and early nineteenth centuries.

PMID- 18331951
TI  - Causal (mis)understanding and the search for scientific explanations: a case
      study from the history of medicine.
AB  - In 1747, James Lind carried out an experiment which proved the usefulness of
      citrus fruit as a cure for scurvy. Nonetheless, he rejected the earlier
      hypothesis of Bachstrom that the absence of fresh fruit and vegetables was the
      only cause of the disease. I explain why it was rational for James Lind not to
      accept Bachstrom's explanation. I argue that it was the urge for scientific
      understanding that guided Lind in his rejection and in the development of his
      alternative theory that humidity was the primary cause of the disease. Central in
      this process was the search for causal mechanisms which could provide
      understanding of how the disease developed and which fitted in with the knowledge
      of the time. Given that the relevant background knowledge and statistical methods
      were not yet available to Lind, he was right to prefer his own explanation to
      that of Bachstrom. Although his explanation turned out to be wrong, and
      Bachstrom's right, from a historical point of view it offered deeper causal
      understanding of both the development of the disease and the preventive and
      curative effects of fresh vegetable food. This case study illustrates how the
      search for causal mechanisms can not only be enlightening, but also very
      misleading.

PMID- 18331952
TI  - Reverend Paley's naturalist revival.
AB  - This paper analyzes the remarkable popularity of William Paley's argument from
      design among contemporary naturalists in biology and the philosophy of science.
      In philosophy of science Elliott Sober has argued that creationism should be
      excluded from the schools not because it is not science but because it is 'less
      likely' than evolution according to fairly standard confirmation theory.
      Creationism is said to have been a plausible scientific option as presented by
      Paley but no longer to be acceptable according to the same standards that once
      approved it. In biology C. G. Williams and Richard Dawkins have seen in Paley a
      proto-adaptationist. This paper shows that the historical assumptions of Sober's
      arguments are wrong and that the philosophical arguments themselves take
      alternatives to science to be alternatives in science and conflate the null
      hypothesis, chance, with a competing explanatory hypothesis. It is also shown
      that the similarity of Paley's adaptationism to that of contemporary biology is
      not what it is made out to be.

PMID- 18331953
TI  - Darwin and the linguists: the coevolution of mind and language, part 2. The
      language-thought relationship.
AB  - This paper examines Charles Darwin's idea that language-use and humanity's unique
      cognitive abilities reinforced each other's evolutionary emergence-an idea Darwin
      sketched in his early notebooks, set forth in his Descent of man (1871), and
      qualified in Descent's second (1874) edition. Darwin understood this coevolution
      process in essentially Lockean terms, based on John Locke's hints about the way
      language shapes thinking itself. Ironically, the linguist Friedrich Max Muller
      attacked Darwin's human descent theory by invoking a similar thesis, the German
      romantic notion of an identity between language and thought. Although Darwin
      avoided outright contradiction, when he came to defend himself against Muller's
      attacks, he undercut some of his own argumentation in favor of the coevolution
      idea. That is, he found it difficult to counter Muller's argument while also
      making a case for coevolution. Darwin's efforts in this area were further
      complicated by British and American writers who held a naturalistic view of
      speech origins yet still taught that language had been invented by fully evolved
      homo sapiens, thus denying coevolution.

PMID- 18331954
TI  - On the validity of Freud's dream interpretations.
AB  - In this article I defend Freud's method of dream interpretation against those who
      criticize it as involving a fallacy-namely, the reverse causal fallacy-and those
      who criticize it as permitting many interpretations, indeed any that the
      interpreter wants to put on the dream. The first criticism misconstrues the logic
      of the interpretative process: it does not involve an unjustified reversal of
      causal relations, but rather a legitimate attempt at an inference to the best
      explanation. The judgement of whether or not a particular interpretation is the
      best explanation depends on the details of the case in question. I outline the
      kinds of probabilities involved in making the judgement. My account also helps to
      cash out the metaphors of the jigsaw and crossword puzzles that Freudians have
      used in response to the 'many interpretations' objection. However, in defending
      Freud's method of dream interpretation, I do not thereby defend his theory of
      dreams, which cannot be justified by his interpretations alone.

PMID- 18331955
TI  - In search of the best explanation about the nature of the gene: Avery on
      pneumococcal transformation.
AB  - In this paper I present a model of rational belief change, and I show how to use
      it to obtain a better insight into the debate about the nature of pneumococcal
      transformation, genes and DNA that took place in the forties, as a result of
      Oswald T. Avery's work. The model offers a particular elaboration of the concept
      of inference to the best explanation, along decision theoretic lines. Within this
      framework, I distinguish different senses in which Avery's team can be said to
      have proceeded with caution, thus throwing some light upon a persistent source of
      disagreement among researchers in the history of genetics. In addition, I explain
      why we are entitled to say that rival parties such as physicist Maclyn McCarty
      and biochemist Alfred Mirsky were epistemically rational, in spite of the fact
      that they reached different conclusions on the basis of the same evidence.

PMID- 18331956
TI  - Specialization and medical mycology in the US, Britain and Japan.
AB  - This paper attempts to bring new insights to a long-standing historical debate
      over medical specialization by analyzing the formation of medical mycology, a
      somewhat marginal biomedical discipline that emerged in the mid-twentieth century
      around studies of fungal disease in humans. The study of fungi predates that of
      bacteria and viruses, but from the 1880s it became eclipsed by bacteriology.
      However, in the postwar period, there were moves to establish medical mycology as
      an independent speciality. I trace the processes that led to the launch of
      professional societies in the United States, Britain and Japan, three major
      players in medical mycology, and more broadly in biomedicine. The analysis of the
      three different national contexts illustrates how geographical, medico
      technological, epidemiological, political and social conditions gave the
      specialty a distinctive character in each country; this was further complicated
      by the different and changing medical fields in which fungal diseases were
      studied and treated. The three case studies show medical specialization as a
      process that is not simply cumulative but responds to specific historical events
      and developments.

PMID- 18331957
TI  - Making way for molecular biology: institutionalizing and managing reform of
      biological science in a UK university during the 1980s and 1990s.
AB  - Historians agree that the second half of the twentieth century saw widespread
      changes in the structure of biological science in universities. This shift was,
      and continues to be, characterized by the de-differentiation of nineteenth and
      early twentieth century disciplines, with increasing emphasis on the methods and
      authority of molecular fields. Yet we currently lack appreciation of the dynamics
      that underpinned these changes, and of their tangible effects on the working
      practices of those involved. In this article we examine the wholesale reform of
      biological science at the University of Manchester, England, that occurred in two
      successive steps in 1986 and 1993. We examine how reform was enabled by economic
      and political factors, as staff seized upon national pressures; in so doing, we
      emphasize how this reform was shaped by a generational view of the biological
      sciences as a one field, unified by molecular techniques. We assess how the
      success of these reforms was tied to new management policies that rewarded
      research activity in molecular fields, and refigured teaching as a punishment for
      research inactivity. We close by showing how our analysis fits amongst, and can
      contribute to, 'big picture' debates in the history and sociology of knowledge.

PMID- 18331958
TI  - Invisible genomes: the genomics revolution and patenting practice.
AB  - In the mid-1990s, the company Human Genome Sciences submitted three potentially
      revolutionary patent applications to the US Patent and Trademark Office, each of
      which claimed the entire genome sequence of a microorganism. The patent
      examiners, however, objected to these applications, and after negotiation they
      were eventually re-written to resemble more traditional gene patents. In this
      paper, which is based on a study of the patent examination files, we examine the
      reasons why these patent applications were unsuccessful in their original form.
      We show that with respect to utility and novelty, the patent attorney's case
      built on an understanding of the genome as a computer-related invention. The
      patent examiners did not object to the patenting of complete genome sequences as
      computer-related inventions on moral grounds or in terms of the distinction
      between a discovery and an invention. Instead, their objections were based on
      classification, rules and procedure. Rather than patent examiners having a notion
      of a genome that should not be patented, the notion of a 'genome', and the ways
      in which it may be different from a 'gene', played no role in these debates. We
      discuss the consequences of our findings for patenting in the biosciences.

PMID- 18331959
TI  - The biomedical standardization of premenstrual syndrome.
AB  - This essay traces the history of premenstrual syndrome (PMS) in French, British,
      and American medical literature from 1950 to 2004. Aetiological theories,
      treatments and diagnostic criteria have varied over time and place, reflecting
      local conditions and changing notions of objectivity and evidence. During the
      1970s researchers in each nation utilised different research strategies to
      overcome variation and contradictory results characteristic of PMS research.
      Since the 1980s, attempts have been made to standardise research internationally
      through prospective daily rating questionnaires that diagnose and measure PMS.
      Amidst controversy, a psychiatric reformulation of the syndrome was included in
      the Diagnostic and Statistical Manual of Mental Disorders (DSM). While the
      diagnostic criteria for this psychiatric category, now called premenstrual
      dysphoric disorder (PMDD), are widely accepted for research purposes, efforts to
      transfer them to medical practice have been less successful. PMDD remains a
      contested disease construct.

PMID- 18331960
TI  - Why don't zebras have machine guns? Adaptation, selection, and constraints in
      evolutionary theory.
AB  - In an influential paper, Stephen Jay Gould and Richard Lewontin (1979) contrasted
      selection-driven adaptation with phylogenetic, architectural, and developmental
      constraints as distinct causes of phenotypic evolution. In subsequent
      publications Gould (e.g., 1997a,b, 2002) has elaborated this distinction into one
      between a narrow "Darwinian Fundamentalist" emphasis on "external functionalist"
      processes, and a more inclusive "pluralist" emphasis on "internal structuralist"
      principles. Although theoretical integration of functionalist and structuralist
      explanations is the ultimate aim, natural selection and internal constraints are
      treated as distinct causes of evolutionary change. This distinction is now
      routinely taken for granted in the literature in evolutionary biology. I argue
      that this distinction is problematic because the effects attributed to non
      selective constraints are more parsimoniously explained as the ordinary effects
      of selection itself. Although it may still be a useful shorthand to speak of
      phylogenetic, architectural, and developmental constraints on phenotypic
      evolution, it is important to understand that such "constraints" do not
      constitute an alternative set of causes of evolutionary change. The result of
      this analysis is a clearer understanding of the relationship between adaptation,
      selection and constraints as explanatory concepts in evolutionary theory.

PMID- 18331961
TI  - Is the language of intentional psychology an efficient tool for evolutionists?
AB  - The language of intentional psychology is commonly used as a means of addressing
      issues concerning selection. This habit is generally considered an efficient
      shorthand, but oft-reported misunderstandings leave room for doubt. I stress the
      general point that efficiency of a mode of expression is an empirical matter,
      deserving the same treatment, theoretically and methodologically, as other such
      matters. Mistaken assumptions regarding the relevant cognitive capacities may
      make for inefficient communication, and discourse about human evolution is a
      plausible case in point.

PMID- 18331962
TI  - Could sexual selection have made us psychological altruists?
AB  - Psychological altruism (being motivated by the needs of others) has a tendency to
      produce behaviour that is costly in evolutionary terms. How, then, could the
      capacity for psychological altruism evolve? One suggestion is that it is the
      result of sexual selection. There are, however, two problems that face such an
      account: first, it is not clear that the resulting behaviour would be altruistic
      in the relevant sense, and second, it does not seem to fit with key features of
      our actual helping behaviour. I will argue that both of these problems can be
      avoided if we adopt a modular account of desire formation.

PMID- 18331963
TI  - Clustering humans: on biological boundaries.
AB  - We inquire into the notions of 'boundary' and 'cluster' in the fields of medical
      genetics, pharmacogenetics, and population genetics. First we show that the two
      notions are not well discussed in literature. Then we propose a promising
      explication of them, in which we argue that clustering is always 'property
      laden', that is, fundamentally dependent on decisions about the properties to be
      taken into account. In particular we suggest three different kinds of properties
      (main properties, investigating properties, and catalyzing properties) that have
      a role in these decisions. That is, we conclude that boundaries and clusters
      among humans depend on our way of considering nature. Concepts of 'race' and
      'ethnic group' are discussed too, since they are the most used clusters among
      humans.

PMID- 18331965
TI  - Heart failure in the elderly: how risky is it to be discharged?

PMID- 18331966
TI  - Oxidized proteins in plasma of patients with heart failure: role in endothelial
      damage.
AB  - BACKGROUND: Oxidative stress is increased in the failing heart, and this might
      contribute to the pathogenesis of myocardial remodelling and heart failure (HF).
      AIM: To identify the oxidized proteins in plasma of chronic HF patients and to
      evaluate their possible role in endothelial damage. METHODS: Plasma levels of
      oxidized proteins were measured by immunoassay and by analysis in albumin and
      immunoglobulin depleted plasma using a proteomic approach, in 40 HF patients and
      in 20 age-matched normal subjects. Analysis of the effects of proteins oxidized
      in vitro on human endothelial cell (EC) viability was also performed. RESULTS:
      Plasma levels of oxidized proteins were significantly higher in HF patients than
      in controls (p<0.01). We identified two proteins, alpha-1-antitrypsin and
      fibrinogen, which underwent oxidation. Oxidation of alpha-1-antitrypsin resulted
      in loss of its protease inhibitor activity, thus leading to EC death in the
      presence of elastase. Fibrinogen, when oxidized, became otherwise cytotoxic and
      induced apoptosis in EC. CONCLUSIONS: This study shows that plasma levels of
      oxidized proteins are increased in HF, and permitted the identification of two
      proteins, namely alpha-1-antitrypsin and fibrinogen, which underwent oxidation.
      In vitro results highlighted the potential role of oxidized proteins in the EC
      damage that occurs in HF.

PMID- 18331967
TI  - BNP and NT-proBNP predict echocardiographic severity of diastolic dysfunction.
AB  - AIMS: To evaluate the best combination of clinical parameters and brain
      natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP), to predict diastolic
      dysfunction (DD) in heart failure with preserved left ventricular ejection
      fraction (HF-PLEF) as determined by Doppler-echocardiography. METHODS AND
      RESULTS: HF patients with EF >40% in the CHARM Echocardiographic Substudy were
      included and classified to have normal diastolic function, or mild, moderate or
      severe diastolic dysfunction. Plasma BNP and NT-proBNP levels were measured and
      relevant clinical characteristics recorded. 181 participants were included in
      this analysis, 72 (40%) had moderate to severe DD. A model including age, sex,
      BNP, body mass index, history of atrial fibrillation, coronary artery disease,
      diabetes mellitus, hypertension and left atrial volume was highly predictive of
      moderate to severe DD; AUC 0.81 (0.73-0.88; p<0.0001). Similarly, substitution of
      BNP with NT-proBNP resulted in an AUC 0.79 (0.72-0.87; p<0.0001). In these
      models; BNP>100 pg/ml (OR 6.24 CI 2.42-16.09, p=0.0002), history of diabetes (OR
      3.52 CI 1.43-8.70, p=0.006) and NT-proBNP >600 pg/ml (OR 5.93 CI 2.21-15.92,
      p=0.0004), history of diabetes mellitus (OR 2.75 CI 1.12-6.76, p=0.03)
      respectively remained independent predictors of DD in HF-PLEF. CONCLUSIONS:
      Natriuretic peptides were the strongest independent predictors of DD, as
      determined by Doppler-echocardiography, in HF-PLEF.

PMID- 18331968
TI  - Post-operative imaging of soft tissue sarcomas.
AB  - Soft tissue sarcomas are uncommon malignancies that have a high risk of local
      recurrence despite adequate initial surgery. The aim of follow-up imaging with
      any malignancy is to detect recurrence promptly so that treatment can be
      instigated at the earliest possible opportunity. In this review article, we
      discuss the imaging modalities that can be employed to detect local recurrence
      following surgery for an extremity soft tissue sarcoma. The role of radiographs,
      computed tomography, magnetic resonance imaging and positron emission tomography
      is reviewed followed by a discussion on the imaging modalities useful in the
      detection of metastatic disease. Finally, we present a robust pathway that is
      suggested for the follow-up of patients with an extremity soft tissue sarcoma.

PMID- 18331969
TI  - Thermal ablation of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is the fifth most common cause of cancer, and its
      incidence is increasing worldwide because of the dissemination of hepatitis B and
      C virus infection. Patients with cirrhosis are at the highest risk of developing
      HCC and should be monitored every 6 months to diagnose the tumour at an early,
      asymptomatic stage. Patients with early-stage HCC should be considered for any of
      the available curative therapies, including surgical resection, liver
      transplantation and percutaneous image-guided ablation. Liver transplantation is
      the only option that provides cure of both the tumour and the underlying chronic
      liver disease. However, the lack of sufficient liver donation greatly limits its
      applicability. Resection is the treatment of choice for HCC in non-cirrhotic
      patients, who account for about 5% of the cases in western countries. However, in
      patients with cirrhosis, candidates for resection have to be carefully selected
      to reduce the risk of postoperative liver failure. It has been shown that a
      normal bilirubin concentration and the absence of clinically significant portal
      hypertension are the best predictors of excellent outcomes after surgery.
      However, less than 5% of cirrhotic patients with HCC fit these criteria. Image
      guided percutaneous ablation is the best therapeutic choice for non-surgical
      patients with early-stage HCC. While ethanol injection has been the seminal
      percutaneous technique, radiofrequency ablation has emerged as the most effective
      method for local tumour destruction and is currently used as the primary ablative
      modality at most institutions.

PMID- 18331970
TI  - Radiofrequency ablation of pulmonary tumours: current status.
AB  - Radiofrequency ablation (RFA) for thoracic tumours has emerged as a minimally
      invasive therapy option for primary and secondary lung tumours and has gained
      increasing acceptance for pain palliation. The procedure is well tolerated and
      the complication rates are low. RFA provides the opportunity for localized tissue
      destruction of limited tumour volumes with medium and long term follow-up data
      suggesting that survival figures do parallel those of non-surgical treatment
      modalities. The purpose of this article is to review the status of RFA in lung
      tumours, to emphasize its place in symptomatic palliation and to discuss its
      potential role in conjunction with radiation or systemic therapy.

PMID- 18331971
TI  - Usefulness of contrast-enhanced magnetic resonance imaging for evaluating
      solitary pulmonary nodules.
AB  - Evaluation of solitary pulmonary nodules (SPNs) poses a challenge to
      radiologists. Chest computed tomography (CT) is considered the standard technique
      for assessing morphologic findings and intrathoracic spread of an SPN. Although
      the clinical role of magnetic resonance imaging (MRI) for SPNs remains limited,
      considerable experience has been gained with MRI of thoracic diseases. Dynamic
      MRI and dynamic CT are useful for differentiating between malignant and benign
      SPNs (especially tuberculomas and hamartomas). Furthermore, dynamic MRI is useful
      for assessing tumor vascularity, interstitium, and vascular endothelial growth
      factor expression, and for predicting survival outcome among patients with
      peripheral pulmonary carcinoma. These advantages make dynamic MRI a promising
      method and a potential biomarker for characterizing tumor response to anti
      angiogenic treatment as well as for predicting survival outcomes after treatment.

PMID- 18331972
TI  - Bradykinin stimulates prostaglandin E2 production and cyclooxygenase activity in
      equine nonglandular and glandular gastric mucosa in vitro.
AB  - REASONS FOR PERFORMING STUDY: There are few data available regarding regulation
      of prostaglandin (PG) generation by equine gastric mucosae and the role of the
      cyclooxygenase (COX) isoforms in their production. OBJECTIVES: To: 1)
      characterise and quantify PGE2 output in vitro; 2) examine the sensitivity of
      PGE2 production to exogenous bradykinin (BK) exposure; 3) determine the
      contribution of the COX-1 and COX-2 pathways to basal and BK-stimulated PGE2
      production; and 4) measure if BK influences electrogenic ion transport in equine
      gastric mucosae in vitro. METHODS: Full thickness gastric sheets were obtained
      from horses at post mortem, stripped of muscle layers and mounted in Ussing
      chambers. Tissues were exposed to bradykinin (BK, 0.1 micromol/l) either alone,
      or following pretreatment with a selective COX-2 inhibitor (NS-398, 1 micromol/l)
      or a nonselective COX inhibitor (piroxicam, 1 micromol/l), or were untreated.
      RESULTS: BK administration increased PGE2 output from the basolateral but not the
      apical faces of both tissue types. Piroxicam, but not NS-398, reduced basolateral
      PGE2 release below control levels in both tissue types. Both piroxicam and NS-398
      pretreatment inhibited BK-stimulated PGE2 release. In separate experiments, BK
      was without effect upon electrophysiological parameters of tissues mounted in
      Ussing chambers. CONCLUSIONS: PGE2 is produced by the nonglandular and glandular
      equine gastric mucosae in vitro. Significantly more PGE2 is released
      basolaterally than apically. BK stimulated the production of PGE2 from the
      basolateral side of both tissue types. These findings suggest that COX-1 is a
      significant pathway for basal PGE2 production from the basolateral faces of both
      nonglandular and glandular equine gastric mucosae in vitro.

PMID- 18331973
TI  - Visual signals of status and rival assessment in Polistes dominulus paper wasps.
AB  - Aggressive competition is an important aspect of social interactions, but
      conflict can be costly. Some animals are thought to minimize the costs of
      conflict by using conventional signals of agonistic ability (i.e. badges of
      status) to assess rivals. Although putative badges have been found in a range of
      taxa, little research has tested whether individuals use badges to assess
      potential rivals before they engage in aggressive contests. Here, choice trials
      were used to test how the variable black facial patterns in Polistes dominulus
      wasps are used during rival assessment. Focal wasps were given access to two
      patches of food, each guarded by a wasp whose facial pattern had been
      experimentally altered. Wasps chose food patches based on the facial pattern of
      the guard, preferring to challenge guards with facial patterns indicating a low
      level of quality, while avoiding guards with facial patterns indicating a high
      level of quality. Therefore, status badges play an important role during rival
      assessment; paper wasps use facial patterns alone to quickly assess the agonistic
      abilities of strangers.

PMID- 18331974
TI  - A new, nearly complete stem turtle from the Jurassic of South America with
      implications for turtle evolution.
AB  - Turtles have been known since the Upper Triassic (210Myr old); however, fossils
      recording the first steps of turtle evolution are scarce and often fragmentary.
      As a consequence, one of the main questions is whether living turtles
      (Testudines) originated during the Late Triassic (210Myr old) or during the
      Middle to Late Jurassic (ca 160Myr old). The discovery of the new fossil turtle,
      Condorchelys antiqua gen. et sp. nov. from the Middle to Upper Jurassic (ca 160
      146Myr old) of South America (Patagonia, Argentina), presented here sheds new
      light on early turtle evolution. An updated cladistic analysis of turtles shows
      that C. antiqua and other fossil turtles are not crown turtles, but stem turtles.
      This cladistic analysis also shows that stem turtles were more diverse than
      previously thought, and that until the Middle to Upper Jurassic there were
      turtles without the modern jaw closure mechanism.

PMID- 18331975
TI  - Specialized shell-breaking crab claws in Cretaceous seas.
AB  - Here we report on a large brachyuran crab species from the Late Cretaceous of
      Mexico that has claws indicative of highly specialized shell-breaking behaviour.
      This crab possessed dimorphic claws (the right larger than the left), armed with
      several broad teeth, including a curved tooth structure found at the base of the
      movable finger of the right claw. The curved tooth is similar to the one observed
      on claws of many living durophagous crabs that use it as a weapon to peel, crush
      or chip the edges of hard-shelled prey, particularly molluscs. These
      morphological traits suggest that specialized shell-breaking crab predators had
      evolved during the Cretaceous, which contradicts previous findings supporting an
      Early Cenozoic origin for specialized shell crushers within the brachyuran clade.

PMID- 18331976
TI  - Local song elements indicate local genotypes and predict physiological condition
      in song sparrows Melospiza melodia.
AB  - Geographical variation in birdsong is taxonomically widespread and behaviourally
      salient, with females often preferring local over non-local song. However, the
      benefits associated with this preference remain poorly understood. One potential
      explanation is that song may reflect a male's place of origin and thus allow
      females to obtain genes well adapted to the local environment. We studied
      naturally occurring variation in the degree to which the elements of a male's
      song repertoire matched those of the local population ('syllable sharing') in
      migratory song sparrows (Melospiza melodia melodia). Syllable sharing was
      correlated with genetic similarity to the local population, suggesting that song
      reflects population of origin. Males sharing more syllables also had larger
      testosterone-dependent traits, fewer blood-borne parasites and reduced indicators
      of stress. Our findings are consistent with locally good genes models.
      Alternatively, immigrants' condition may suffer due to unfamiliarity with the
      breeding site or inability to match song elements during territorial
      interactions. Females preferring 'local-sounding' males may thus obtain genetic
      and/or direct benefits for their offspring.

PMID- 18331977
TI  - Influence of epidermal hydration on the friction of human skin against textiles.
AB  - Friction and shear forces, as well as moisture between the human skin and
      textiles are critical factors in the formation of skin injuries such as blisters,
      abrasions and decubitus. This study investigated how epidermal hydration affects
      the friction between skin and textiles.The friction between the inner forearm and
      a hospital fabric was measured in the natural skin condition and in different
      hydration states using a force plate. Eleven males and eleven females rubbed
      their forearm against the textile on the force plate using defined normal loads
      and friction movements. Skin hydration and viscoelasticity were assessed by
      corneometry and the suction chamber method, respectively.In each individual, a
      highly positive linear correlation was found between skin moisture and friction
      coefficient (COF). No correlation was observed between moisture and elasticity,
      as well as between elasticity and friction. Skin viscoelasticity was comparable
      for women and men. The friction of female skin showed significantly higher
      moisture sensitivity. COFs increased typically by 43% (women) and 26% (men) when
      skin hydration varied between very dry and normally moist skin. The COFs between
      skin and completely wet fabric were more than twofold higher than the values for
      natural skin rubbed on a dry textile surface.Increasing skin hydration seems to
      cause gender-specific changes in the mechanical properties and/or surface
      topography of human skin, leading to skin softening and increased real contact
      area and adhesion.

PMID- 18331978
TI  - Modelling heterogeneity and the impact of chemotherapy and vaccination against
      human hookworm.
AB  - There is a growing emphasis on the development of vaccines against helminths
      (worms), and mathematical models provide a useful tool to assess the impact of
      new vaccines under a range of scenarios. The present study describes a stochastic
      individual-based model to assess the relative impact of chemotherapy and
      vaccination against human hookworm infection and investigates the implications of
      potential correlations between risk of infection and vaccine efficacy.
      Vaccination is simulated as a reduction in susceptibility to infection and the
      model includes population heterogeneities and dynamical waning of protection. To
      help identify appropriate measures of vaccine impact, we present a novel
      framework to quantify the vaccine impact on the infection-associated morbidity
      and introduce a measure of symmetry to study the correspondence between reduction
      in intensity and reduction in morbidity. Our modelling shows that, in high
      transmission settings, the greatest impact of vaccination will be attained when
      vaccine efficacy is the greatest among individuals harbouring the heaviest worm
      burdens, and that the decline of morbidity primarily depends on the level of
      protection attained in the most at risk 8-12% of the population. We also
      demonstrate that if risk of infection and vaccine protection are correlated,
      there is not always a direct correspondence between the reduction in worm burden
      and in morbidity, with the precise relationship varying according to transmission
      setting.

PMID- 18331979
TI  - Automatic identification of bird targets with radar via patterns produced by wing
      flapping.
AB  - Bird identification with radar is important for bird migration research,
      environmental impact assessments (e.g. wind farms), aircraft security and radar
      meteorology. In a study on bird migration, radar signals from birds, insects and
      ground clutter were recorded. Signals from birds show a typical pattern due to
      wing flapping. The data were labelled by experts into the four classes BIRD,
      INSECT, CLUTTER and UFO (unidentifiable signals). We present a classification
      algorithm aimed at automatic recognition of bird targets. Variables related to
      signal intensity and wing flapping pattern were extracted (via continuous wavelet
      transform). We used support vector classifiers to build predictive models. We
      estimated classification performance via cross validation on four datasets. When
      data from the same dataset were used for training and testing the classifier, the
      classification performance was extremely to moderately high. When data from one
      dataset were used for training and the three remaining datasets were used as test
      sets, the performance was lower but still extremely to moderately high. This
      shows that the method generalizes well across different locations or times. Our
      method provides a substantial gain of time when birds must be identified in large
      collections of radar signals and it represents the first substantial step in
      developing a real time bird identification radar system. We provide some
      guidelines and ideas for future research.

PMID- 18331980
TI  - Informational conflicts created by the waggle dance.
AB  - The honeybee (Apis mellifera) waggle dance is one of the most intriguing animal
      communication signals. A dancing bee communicates the location of a profitable
      food source and its odour. Followers may often experience situations in which
      dancers indicate an unfamiliar location but carry the scent of a flower species
      the followers experienced previously at different locations. Food scents often
      reactivate bees to resume food collection at previously visited food patches.
      This double function of the dance creates a conflict between the social vector
      information and the private navigational information. We investigated which kind
      of information followers with field experience use in this situation and found
      that followers usually ignored the spatial information encoded by the waggle
      dance even if they followed a dance thoroughly (five waggle runs or more). They
      relied on private information about food source locations instead (in 93% of all
      cases). Furthermore, foragers preferred to follow dancers carrying food odours
      they knew from previous field trips, independently of the spatial information
      encoded in the dance. Surprisingly, neither odour identity nor the location
      indicated by the dancer was an important factor for the reactivation success of a
      dance. Our results contrast with the assumption that (i) followers usually try to
      decode the vector information and (ii) dances indicating an unfamiliar location
      are of little interest to experienced foragers.

PMID- 18331981
TI  - Strategic adjustment of begging effort by banded mongoose pups.
AB  - Variation in the intensity of conspicuous displays raises three basic questions:
      (i) the relationship between internal state and display intensity, (ii) the
      relationship between display intensity and receiver response, and (iii) the
      effect of variation in receiver responsiveness on signaller behaviour. Here, I
      investigate the interaction between pups and helpers in the communally breeding
      banded mongoose (Mungos mungo), where each pup forms an exclusive relationship
      with a single adult helper (termed its 'escort'). By experimentally manipulating
      pup need, I demonstrate that changes in begging rate correspond to changes in
      short-term need. The data then suggest that escorts in good condition may be more
      responsive to increased begging and that pups associating with them increase
      their begging more than do pups paired with escorts in poor condition. Escorts
      also appear more responsive to increased begging by female pups, and female pups
      increase their begging more than do male pups. These results suggest that banded
      mongoose pups may strategically adjust their investment in begging in relation to
      variation in the expected pay-off. I argue that such adjustment is likely to be a
      general phenomenon: wherever there is variation in responsiveness to signals,
      signallers will be selected to identify different categories of receiver and
      adjust their signals in order to maximize the pay-offs. Therefore, differences in
      signal intensity may be as much a product of context as an indication of
      variation in individual phenotypic or genotypic state.

PMID- 18331982
TI  - Function of bright coloration in the wasp spider Argiope bruennichi (Araneae:
      Araneidae).
AB  - There are two major competing explanations for the counter-intuitive presence of
      bright coloration in certain orb-web spiders. Bright coloration could lure insect
      prey to the web vicinity, increasing the spider's foraging success.
      Alternatively, the markings could function as disruptive camouflage, making it
      difficult for the insect prey to distinguish spiders from background colour
      variation. We measured the prey capture rates of wasp spiders, Argiope
      bruennichi, that were blacked out, shielded from view using a leaf fragment, or
      left naturally coloured. Naturally coloured spiders caught over twice the number
      of prey as did either blacked-out or leaf-shielded spiders, and almost three
      times as many orthopteran prey. Spectrophotometer measurements suggest that the
      bright yellow bands on the spider's abdomen are visible to insect prey, but not
      the banding on the legs, which could disguise the spider's outline. Thus, our
      results provide strong support for the hypothesis that bright coloration in the
      wasp spider acts as a visual lure for insect prey and weak support for the
      hypothesis that the arrangement of the banding pattern across the spider's body
      disguises the presence of the spider on the web.

PMID- 18331983
TI  - Comparing the strength of behavioural plasticity and consistency across
      situations: animal personalities in the hermit crab Pagurus bernhardus.
AB  - Many phenotypic traits show plasticity but behaviour is often considered the
      'most plastic' aspect of phenotype as it is likely to show the quickest response
      to temporal changes in conditions or 'situation'. However, it has also been noted
      that constraints on sensory acuity, cognitive structure and physiological
      capacities place limits on behavioural plasticity. Such limits to plasticity may
      generate consistent differences in behaviour between individuals from the same
      population. It has recently been suggested that these consistent differences in
      individual behaviour may be adaptive and the term 'animal personalities' has been
      used to describe them. In many cases, however, a degree of both behavioural
      plasticity and relative consistency is probable. To understand the possible
      functions of animal personalities, it is necessary to determine the relative
      strength of each tendency and this may be achieved by comparison of statistical
      effect sizes for tests of difference and concordance. Here, we describe a new
      statistical framework for making such comparisons and investigate cross
      situational plasticity and consistency in the duration of startle responses in
      the European hermit crab Pagurus bernhardus, in the field and the laboratory. The
      effect sizes of tests for behavioural consistency were greater than for tests of
      behavioural plasticity, indicating for the first time the presence of animal
      personalities in a crustacean model.

PMID- 18331984
TI  - Pushing versus pulling: division of labour between tarsal attachment pads in
      cockroaches.
AB  - Adhesive organs on the legs of arthropods and vertebrates are strongly direction
      dependent, making contact only when pulled towards the body but detaching when
      pushed away from it. Here we show that the two types of attachment pads found in
      cockroaches (Nauphoeta cinerea), tarsal euplantulae and pretarsal arolium, serve
      fundamentally different functions. Video recordings of vertical climbing revealed
      that euplantulae are almost exclusively engaged with the substrate when legs are
      pushing, whereas arolia make contact when pulling. Thus, upward-climbing
      cockroaches used front leg arolia and hind leg euplantulae, whereas hind leg
      arolia and front leg euplantulae were engaged during downward climbing. Single
      leg friction force measurements showed that the arolium and euplantulae have an
      opposite direction dependence. Euplantulae achieved maximum friction when pushed
      distally, whereas arolium forces were maximal during proximal pulls. This
      direction dependence was not explained by the variation of shear stress but by
      different contact areas during pushing or pulling. The changes in contact area
      result from the arrangement of the flexible tarsal chain, tending to detach the
      arolium when pushing and to peel off euplantulae when in tension. Our results
      suggest that the euplantulae in cockroaches are not adhesive organs but 'friction
      pads', mainly providing the necessary traction during locomotion.

PMID- 18331985
TI  - Robust bi-level optimization models in transportation science.
AB  - Mathematical programmes with equilibrium constraints (MPECs) constitute important
      modelling tools for network flow problems, as they place 'what-if' analyses in a
      proper mathematical framework. We consider a class of stochastic MPEC traffic
      models that explicitly incorporate possible uncertainties in travel costs and
      demands. In stochastic programming terminology, we consider 'here-and-now' models
      where decisions must be made before observing the uncertain parameter values and
      the responses of the network users; the objective is to minimize the expectation
      of the upper-level objective function. Such a model could, for example, be used
      to derive a fixed toll pricing scheme that provides the best revenue for a given
      network over a time period, where variations in traffic conditions and demand
      elasticities are described by distributions of parameters in the travel time and
      demand functions. We present new results on the stability of globally optimal
      solutions to perturbations in the probability distribution, establishing the
      robustness of the model. We also discuss penalization and discretization
      algorithms, the latter enabling the use of standard MPEC algorithms, and provide
      many future research avenues.

PMID- 18331986
TI  - Short messages.
AB  - This paper has three purposes. The first one is to explain to a general audience
      what is involved in retrieving a web page or performing some other complex
      network transaction, and what can make it slow, and why the problem of slowness
      is likely to get worse as networked applications become more complex. The second
      is to describe, to those who program networked applications, certain facts that
      we have learnt from modelling communication networks, notably the fact of heavy
      tailed distributions in traffic, which may allow more efficient applications to
      be written. The third is to describe to network modellers an interesting class of
      problems relating to algorithm design for communication networks.

PMID- 18331987
TI  - A review of the diversity and evolution of photonic structures in butterflies,
      incorporating the work of John Huxley (The Natural History Museum, London from
      1961 to 1990).
AB  - The photonic structures of butterfly wings are among the most anatomically
      diverse of all those in nature, giving rise to an unrivalled display of
      structural colours. These have recently become the focus of research by workers
      in a variety of disciplines, stimulated by their potential applications to
      technology ('biomimetics'). This interest, together with the discovery of
      unpublished electron micrographs taken by the late Dr John Huxley (Natural
      History Museum, London), prompted this review of butterfly photonics in general.
      The current work provides a synopsis of the literature to date, covering the
      diversity and evolution of these optical structures and incorporating Huxley's
      work, which represents an important biomimetic and evolutionary database on its
      own. This review deals with butterfly photonic devices according to the parts of
      the butterfly scales on which they occur. In this way, the information is ripe
      for evolutionary study.

PMID- 18331988
TI  - From empirical patterns to theory: a formal metabolic theory of life.
AB  - The diversity of life on Earth raises the question of whether it is possible to
      have a single theoretical description of the quantitative aspects of the
      organization of metabolism for all organisms. However, similarities between
      organisms, such as von Bertalanffy's growth curve and Kleiber's law on metabolic
      rate, suggest that mechanisms that control the uptake and use of metabolites are
      common to all organisms. These and other widespread empirical patterns in biology
      should be the ultimate test for any metabolic theory that hopes for generality.
      The present study (i) collects empirical evidence on growth, stoichiometry,
      feeding, respiration and energy dissipation and exhibits it as stylized
      biological facts; (ii) formalizes assumptions and propositions in a metabolic
      theory that is fully consistent with the Dynamic Energy Budget theory; and (iii)
      proves that these assumptions and propositions are consistent with the stylized
      facts.

PMID- 18331990
TI  - [Strategies for cloning of novel genes based on EST].
AB  - Expressed sequence tags (EST) are short, randomly selected single-pass nucleotide
      sequence reads derived from cDNA libraries and represent a small part of a gene.
      Along with the development of bioinformatics and genetic localization, EST has
      already become a powerful tool for mapping, cloning and expression profiling of
      genes. Recently, because of the fast distension of EST databases, application of
      EST in gene mapping and cloning leads to revolutionary change in the strategies
      for cloning of novel genes. Despite of some insufficiencies, it has been proved
      that EST could promote the discovery and research of novel genes. In this
      article, an introduction about EST, especially EST-based strategies for cloning
      of novel genes will be given in details.

PMID- 18331991
TI  - [Association between mitochondrial DNA mutations and cancer in human].
AB  - Mitochondria are essential organelles that generate cellular energy in cells.
      Mutations of mitochondrial DNA (mtDNA) have been identified in various types of
      cancer, suggesting a complex relationship between mtDNA and cancer. This review
      focuses on the possible correlation between the mtDNA mutation and cancer.
      Additionally, possible causes for mtDNA mutations and applications for detecting
      mtDNA mutations in cancer are discussed.

PMID- 18331992
TI  - [Progress in the study of genetic diversity of Mongolian horse].
AB  - Mongolian horse is a kind of important breed resource of local horses in our
      country. It has a lot of advantages such as powerful endurance, rough feeding
      resistance, and strong disease resistance. These advantages have become driving
      force for in-depth study on Mongolian horse. Genetic diversity can reflect all
      the genetic information of a species or a variety, namely, it reflects the
      richness of genetic diversity and confirms the degree of uniqueness of genetic
      resources through genetic markers. This paper introduces the progress in the
      study on genetic diversity of Mongolian horse in many aspects such as in cell,
      biochemical and molecular level, and highlights the various hot gene types and
      their polymorphisms.

PMID- 18331993
TI  - [Use of Apc(Min/+) mouse model in the studies of intestinal tumors].
AB  - More than thirty kinds of mutant or knockout mice bearing intestinal neoplasm
      have been reported up to the present. Apc(Min/+) mouse holding multiple
      intestinal neoplasia, provides an appropriate model to evaluate human familial
      adenomatous polyposis. APC is an important tumor-suppressor gene in the Wnt
      pathway, which is involved in the pivotal signal transduction cascade in animal
      embryogenesis and colorectal carcinogenesis. Apc(Min/+) mouse model was presented
      as aspects of the strain background, genotype/phenotype, divergent canonical Wnt
      signaling pathway, methylation of tumor-suppressor gene, TGF-b signaling pathway
      and multidrug resistance gene, etc. This review also introduced the application
      and signification of the mouse model in studies of anti-colorectal tumor drugs.

PMID- 18331994
TI  - [Activation tagging and its application in plant functional genomics research].
AB  - It is a practical strategy to screen for mutants in the research of plant
      functional genomics. Comparing with classical T-DNA knock-out mutagenesis
      technology by the loss-of-function mutation, the activation T-DNA tagging
      technique based on the gain-of-function mutation has its own particular
      advantages, mainly characterized by producing dominant mutants of genes with
      functional redundancy and easily cloning of the genes. First, the basic principle
      of activation tagging, and the progress of its application in the research on
      plant functional genomics was reviewed, especially in Arabidopsis and rice. The
      recent research progress in the mechanism of plant biotic and abiotic stress
      tolerance and of plant development unraveled by the method of activation tagging
      was then addressed. Finally, the limitation and prospects of this technique were
      discussed.

PMID- 18331995
TI  - [Research progress on diacylgycerol acyltransferase 2 (DGAT2) gene].
AB  - Diacylgycerol acyltransferase2 (DGAT2) is an important enzyme in many organisms.
      DGAT2 catalyzes the final step of triacylglycerol (TAG) biosynthesis by
      converting diacylgycerol (DAG) and fatty acyl-coenzyme A (CoA) into TAG. This
      enzyme is encoded by both DGAT2 and DGAT1 genes. This paper reviews the discovery
      of the DGAT2 gene, its structure, chromosomal location and biological effect. The
      relationship between its genetic polymorphisms and animal performance traits is
      also discussed. The review ends with future prospects.

PMID- 18331996
TI  - [Microarray-based methods to identify DNA methylation in cancer].
AB  - DNA methylation is an epigenetic modification associated with gene transcription
      regulation, X-chromosome inactivation, regulation of development and cell
      differentiation. Aberrant DNA methylation has been linked to cancer. The advent
      of microarray technology has provided new opportunities for high-throughput study
      on DNA methylation. Various microarray-based methods depend on different
      pretreatments including immunoprecipitation and restriction digestion. Al-though
      each technique has its limitations, the immunoprecipitation method has high
      specificity, and the restriction digestion method shows high sensitivity.
      Together they provide many choices to the study of genome-wide DNA methylation
      profile in cancer.

PMID- 18331997
TI  - [Association study between PPARGC1A Thr394Thr/ Gly482Ser polymorphisms and type 2
      diabetes].
AB  - To investigate the association between single nucleotide polymorphisms (SNPs)
      rs2970847(Thr394Thr) and rs8192678(Gly482Ser) of peroxisome proliferators
      activated receptor gamma coactivator-1(PPARGC1A)gene and type 2 diabetes in
      Chinese Han population in Hubei. The Thr394Thr and Gly482Ser polymorphisms of the
      PPARGC1A gene were genotyped in 307 controls and 344 type 2 diabetes patients.
      Single marker/haplotype association analyses and logistic re-gression analysis
      were performed. Significant differences in genotypic and allelic frequencies were
      observed between cases and controls for the Thr394Thr polymorphism (genotype,
      P=0.006; allele, Plt;0.001). The genotype AA of the Thr394Thr polymorphism and
      the haplotype Thr394(ACA)- Ser482 were significantly associated with type 2
      diabetes. No differences in the genotypic and allelic frequencies between cases
      and controls were found for the Gly482Ser polymorphism. PPARGC1A is a
      susceptibility gene for type 2 diabetes in Chinese Han population in Hubei.

PMID- 18331998
TI  - [NF1 mutation analysis in a Chinese family with neuro- fibromatosis type].
AB  - A Chinese family affected with autosomal dominant disorder-neurofibromatosis type
      I was identified in this study. Linkage analysis was performed, and DNA
      sequencing for whole coding region of NF1 was carried out to identify the disease
      causing mutation. The disease gene of the Chinese NF1 family was linked to NF1
      locus, and a nonsense mutation, G1336X in the NF1 gene was identified. This
      mutation truncates the NF1 protein by 1 483 amino acid residues at the C
      terminus, and is co-segregate with all the patients, but not present in
      unaffected individuals in the family. The present study demonstrated that G1336X
      mutation in the NF1 gene cause Neurofibromatosis type I in the family. To our
      knowledge, this mutation is firstly reported in Chinese population.

PMID- 18331999
TI  - [Effects of sample size on the observed number of allele of 9 STR loci with
      various genetic data].
AB  - In the genetic study, the samples can greatly influence the analysis and
      interpretation of the genetic data obtained. Here we examined the effects of
      sample size on the observed number of allele of 9 STR loci (D3S1358, vWA, FGA,
      TH01, TPOX, CSF1PO, D13S317, D5S818, D7S820) with 30 various population genetic
      data. The results show: the quantity of alleles and the quantity of samples was
      not obviously corresponding, while the populations with few samples had more
      allele observed. And there was no significant influence on the quantity of the
      allele observed when the quantity of the samples reached to a certain amount. H
      (heterozygosity) was up to a stable level when the quantity of sample was 50.
      Those who had low heterozygosity (such as TPOX) changed obviously with the
      quantity of samples, while those had high heterozygosity (such as FGA) changed a
      little with the quantity of samples.

PMID- 18332000
TI  - [Distribution of HIV/AIDS associated CCR2-64 I allele of 14 Chinese ethnic
      populations in South China].
AB  - The purpose of the work is to investigate the frequencies and polymorphisms of
      HIV-1 resistant CCR2-64 I alleles in 14 Chinese populations in South China. The
      blood samples include 791 unrelated healthy individuals. Whole blood samples were
      collected randomly and their genomic DNA were extracted with OMEGA Blood Kits.
      Allelic frequencies were identified by PCR-RFLP analysis. 636 individuals were
      wild-type homozygous, 104 individuals were CCR2-64 heterozygote and 51
      individuals were CCR2-64 homozygous. Distributions of the CCR2-64 I alleles among
      the populations were in accordance with Hardy-Weinberg equilibrium. The average
      allele frequencies was 13.6%, and the frequency span of the alleles was 1.6%
      30.3%. By statistical analysis, the frequency varied significantly in 14
      populations (Plt;0.05). Among them, Zhuang ethnic population had the lowest CCR2
      64 I allele, whereas the Lisu ethnic population in Yunnan province had the
      highest CCR2-64 I allele Conclusion: The frequency of CCR2-64 I allele of 12
      ethnic populations were lower than that of Han. The frequency of CCR2-64 I allele
      between Southern and South-east group showed significant variations. The mutant
      alleles conferring genetic resistance to HIV-1 and AIDS progression needs to be
      further studied.

PMID- 18332001
TI  - [African origin of Chinese domestic donkeys].
AB  - Analysis of the 367 mtDNA D-loop sequences (of which 241 sequences were collected
      from literature) of 399 bp in 13 Chinese domestic donkey breeds revealed 96
      different haplotypes with 57 polymorphic sites. The haplotype diversity and the
      nucleotide diversity were 0.767-0.967 and 0.014-0.032, respectively, indicating
      abundant genetic diversity in Chinese domestic donkeys. The Neighbor-joining tree
      of Chinese domestic donkey sequences was constructed with 3 Nubian wild ass
      sequences, 3 Somali wild ass sequences and 6 Asian wild ass sequences. Our
      results suggest that the maternal ancestor of Chinese domestic donkeys is highly
      likely to be Somali and Nubian of African wild ass instead of Asian wild ass.

PMID- 18332002
TI  - [Association of polymorphisms of DGAT2 gene with growth traits in Jiaxian red
      cattle].
AB  - The polymorphisms of DGAT2 gene in 92 Jiaxian red cattle were analyzed using PCR
      RFLP method. Results showed that the PCR products digested with TaqI demonstrated
      polymorphisms, and showed two kinds of genotype: AA and AB. This polymorphic
      locus of DGAT2 gene was at Hardy-Weinberg equilibrium (P>0.05). The results of
      general linear model analysis showed that polymorphisms of DGAT2 gene had
      significant association (Plt;0.05) with body weight and body length, while had no
      significant association with others growth traits (P>0.05). Therefore, genotype
      AB may have positive effect on body weight.

PMID- 18332003
TI  - [Expression profiles of the extracellular matrix-associated genes during rat
      liver regeneration].
AB  - It has been well known that the extracellular matrix (ECM) plays an important
      role in cell polarization, cell adhesion, cell proliferation, morphogenesis and
      differentiation. For the sake of the further in-depth investigation of the
      changes and actions of ECM in liver regeneration (LR) at gene transcriptional
      level, the ECM-associated genes were obtained by databases searching and
      literature retrieving, subsequently their expression profiles in rat regenerating
      liver were detected using Rat Genome 230 2.0 array, then LR-associated genes were
      identified based on comparison of the gene expression difference between sham
      operation (SO) group and partial hepatectomy (PH) group. A total of 97 genes were
      verified to be LR-associated. The initially and totally expressed number of these
      genes occurring in initial phase of LR, G0/G1 transition, cell proliferation,
      cell differentiation and structure-functional reconstruction were 49, 19, 43, 5
      and 84, 51, 369, 144, respectively, illustrating that expression of the ECM
      associated genes were initiated mainly in the early phase, working in differ-ent
      phases. Their expression similarity was classified into 5 groups including only
      up-, predominantly up-, only down-, predominantly down-, and equal in up
      regulated and down-regulated, involving 38, 21, 21, 10 and 7 genes, respectively;
      the number of up-regulated expressed genes and down-regulated expressed ones was
      411 and 186; their expression patterns were categorized into 24 types, showing
      that the physiological and biochemical activities in LR were characterized by
      phase, diversity and intricacy. According to expression profiles and expression
      patterns of the ECM-associated genes in LR, it was confirmed that the levels of
      the below-listed genes in expression increased at the corresponding phases of LR,
      including fibronectin-associated genes at early phase in LR, and collagen
      associated genes at middle phase.

PMID- 18332004
TI  - [Generation of bone morphogenetic protein 4 conditional RNA interference mice].
AB  - To explore bone morphogenetic protein 4 (BMP4) function in the developing bone, a
      BMP4 conditional RNA interference (CRNAi) vector was constructed based on the
      pBSK/U6 vector with a LoxPneo cassette. The transgene fragment targeting bmp4 was
      obtained by Kpn and Afl double digestion and was purified before being
      microinjected into fertilized eggs from FVB/NJ mice. BMP4CRNAi transgenic mice
      were genotyped by PCR. And the PCR positive mice were crossed with Col2a1-Cre
      transgenic mice, whose Cre recombinase was specifically expressed in osteo
      chondro-progenitor cells. Bmp4 mRNA expression in primary chondrocytes were
      examined by semi-quantitive RT-PCR to determine RNA interference efficiency.
      Results showed that BMP4(CRNAi) mice and BMP4 (Col2a1-CRNAi) mice were produced
      successfully, and bmp4 knockdown efficiency in primary chondrocytes of BMP4
      Col2a1-CRNAi mice was 81%. This transgenic mouse line provides excellent model
      for studying the role of BMP4 in chondrocyte development, and BMP4CRNAi mouse may
      be a good model for studying the role of BMP4 in different cells, tissues and
      organs through crossing with different Cre transgenic mice.

PMID- 18332005
TI  - [Cloning of gene fragment of estrogen receptor-beta and its expression in mouse
      embryo].
AB  - In order to study the expression and regulation effects of estrogen receptor-beta
      (ERbeta) in the development of mouse embryo, the primer of ERbeta was designed,
      the ERbeta fragment was first obtained by RT-PCR and subcloned into plasmids pGEM
      3Z, then the recombinant plasmids were linearized with the restriction enzymes
      of EcoRand Hind. Using Sp6 and T7 RNA polymerase, the digoxigenin(dig) labeled
      sense and anti-sense probes were transcriped in vitro, respectively. Then the
      expression of ERbeta in mouse embryo was examined with the probes by whole-mount
      in situ hybridization. The results indicated that ERbeta is expressed in the
      brain, spinal neural tube, genital ridge, pericardium, limb bud and mandibular
      arch of 10.5 dpc embryo, and is also expressed in the telencephalon,
      mesencephalon, medulla oblongata, spinal cord and limb bud of 13.5 dpc embryo.
      These results suggest that ERbeta maybe play a role of regulation in sexual
      differentiation, primal differentiation of neural tube, further differentiation
      of three primary cerebral vesicles and spinal cord, generation and
      differentiation of bone and cartilage of limb bud, development of pericardium and
      configuration differentiation of mandibular in mouse embryo.

PMID- 18332006
TI  - [Cloning and sequence analysis of TSEG-1, a novel gene specifically expressed in
      mouse testis].
AB  - The expressed sequence tags (ESTs) of normal mouse testis were obtained from
      online EST database ZooDDD. Their highly homologous EST sequences were found
      through the dbEST database to construct contigs, and spliced by the biomedical
      software Biolign. The corresponding exons and introns within genome sequences
      were predicted by software GeneScan. According to the open reading frame, the
      primers were designed. RT-PCR was applied in the cloning of novel gene from mouse
      testis and analyzing its expression pattern in various mouse tissues. The
      bioinformatics analysis on the sequencing results of TSEG-1 was conducted.
      Results indicated that a novel gene TSEG-1 was cloned from 1 668-2 011 kb of
      mouse X chromosome, with full-length sequence of 510 bp. The open reading frame
      (ORF) is 336 bp in length and en-codes a deduced amino acid sequence of 111
      residues. The molecular weight of TSEG-1 protein is 12.84258 kDa, and its pI is
      11.4000. RT-PCR demonstrated the correctness of its ORF. TSEG-1 was distinctively
      expressed in testis, but not in other tissues of mouse. No obvious homology with
      other mouse cDNA was found for TSEG-1. The GenBank accession number EU079024 was
      achieved. It was predicted that TSEG-1 is a kind of transmembrane protein, and
      the transmembrane domain is from 41 amino acid residue to 61 amino acid residue.
      Blastn analysis revealed its high homology to human testis-specific gene H2AX.
      Computational prediction of the 5'-untranslated region of TSEG-1 gene revealed a
      680 bp-length promoter region. There are four antigen binding sites and two
      phosphorylation sites of specific protein kinase in TSEG-1 protein, with
      subcellular localization in mitochondria. The cloning of mouse testis specific
      gene TSEG-1 laid a foundation for subsequent research of its biological function
      and expression regulation.

PMID- 18332007
TI  - [Analysis of genetic structure of mirror carp population and correlation of
      microsatellite markers and economic traits].
AB  - The genetic structure of one breeding population of mirror carp(Cyprinus carpio
      L.) was analysed using thirty-five polymorphic microsatellite markers. The
      effective number of alleles (Ae), observed heterozygosity (Ho), expected
      heterozygosity (He) and polymorphism information content(PIC) were all
      determined. The Hardy-Weinberg equilibrium was checked by chi-square test. For
      each locus, 2-7 alleles were detected, with a total of 118 alleles for 35 loci .
      The value of Ae, Ho, He and PIC showed that the genetic variation of the
      population was not high .The average effective number of alleles and the mean
      polymorphism information content were 2.16 and 0.42, respectively, and the
      observed and expected heterozygosity were 0.431 and 0.4736 , respectively.The
      probability value of chi-square test showed that more than half of the thirty
      five loci have significantly (Plt;0.01) deviated from Hardy-Weinberg equilibrium.
      The correlation of genotype of each locus and individual phenotype data was
      analysed , and 4 loci seemed associated with body weight and body size . When
      compared with the result of QTL mapping of common carp, HLJ319 locus was
      consistent with the mapping result approximately, which was significantly
      correlated with body size . Several significantly deviated loci were also
      analysed, and the possible cause of the kind of deviation was discussed .

PMID- 18332008
TI  - [Initial functional analysis of the promoter region and coding region of Pib gene
      in transgenic rice].
AB  - The promoter region and intact coding region of Pib gene (9.9 kb) was inserted
      into the downstream of CaMV 35S promoter in a binary vector pPZP2Ha3(+),
      resulting a plasmid pNAR701. And a fragment of Pib gene from 6 986 to 9 392 bp
      was placed into pPZP2Ha3(-) under the control of CaMV 35S promoter, producing an
      antisense expression vector pNAR703. These two recombined vectors were
      transferred into a blast medium susceptible rice cultivar R109 by an
      Agrobecterium-mediated method. Tests of PCR and Southern blotting for transgenic
      plants as well as the segregation of hygromycin resistance in T1 generation
      confirmed that the target DNA fragments were integrated into genome of R109 and
      hereditable. Northern blotting analysis showed the coding region of Pib gene
      double driven by 35S and its native promoter was able to transcript in T1
      transgenic plants. Rice blast resistance test for T1 transgenic seedlings of 3-4
      leaves stage and in vitro leaves in tillering stage showed that transgenic plants
      of pNAR701 were more resistant to blast race ZD1 and ZG1 than the wild type
      plants, but the resistance of antisense transgenic plants from pNAR703 was
      decreased compared to the controls.

PMID- 18332009
TI  - [Cloning and expression analysis of drought-tolerant and wa-ter-saving related
      gene PmMYB in broomcorn millet].
AB  - Exploring novel genes and gene combinations are of primary importance in plant
      drought-tolerance and water-saving research. Based on the EST sequence of MYB
      gene obtained in the research on molecular basis of drought-tolerance and water
      saving in broomcorn millet (Panicum miliaceum L.), a 1 739 bp genomic sequence of
      MYB gene, designated PmMYB, was amplified using primers based on this EST
      sequence and that of rice MYB18. Sequence analysis indicated that PmMYB consisted
      of 2 introns, 121 bp (347-467 bp) and 93 bp (599-691 bp) in length respectively,
      and 3 extrons. The full-length cDNA sequence of PmMYB is 1 525 bp, which includes
      212 bp 3' untranslated region, 41 bp 5' untranslated region, and 1 272 bp coding
      region which encodes 424 amino acids with a serine-rich region. PmMYB is a
      typical R2, R3-MYB transcription factor with its 2 typical DNA-binding domains
      (amino acid sites of 13-63 and 66-114). The multiple alignment of R2, R3 amino
      acid repeat regions of MYB genes among broomcorn millet, rice, corn, loblolly
      pine, Arabidopsis, capsicum, upland cotton, barley and aubergine indicates that
      R2, R3 repeat regions are very conserved. The phylogenetic analysis based on
      amino acid sequence shows that MYB genes are highly divergent with similarity
      ranging from 32% to 84%. PmMYB has the highest similarity (84%) with MYB18 gene
      of rice, whereas 46% and 41% with barley and corn, respectively. Semi
      quantitative RT-PCR confirmed that PmMYB was upregulated by water stress and re
      watering in broomcorn millet. Cloning this gene may provide a good foundation to
      improve the drought-tolerance and water-saving in broomcorn millet as well as in
      other plants.

PMID- 18332010
TI  - [A study on origin of genetic ethics problem and countermeasure].
AB  - The genetic ethical problem is one of problems which are the most disputable or
      difficult to resolve perfectly in the fields of life science. In these years the
      research for the problems is being concentrated on the types of genetic ethical
      problem and the ways to resolve them. But the systematic research for origin of
      genetic ethical problem is rare to be known. Thus it seems to be short of
      theoretical support to bring forward corresponding countermeasure. In this paper
      we focus on the evolving germ of genetic ethical problem and its evolving rule
      from the twofold views of human biological evolution and cultural evolution. A
      human being is a double offspring with biological evolution and cultural
      evolution . And he is a species which has both biological and cultural attribute
      on the earth. Through comparing and studying human biological evolution ,
      cultural evolution, and characteristics of both biological attribute and cultural
      attribute, we bring forward a viewpoint that all ethical problems originate from
      a conflict originating from interplay of human biological evolution and cultural
      evolution. We intend to seek for the gist of theory and practice in order to
      research for genetic ethical problem and put forward some corresponding
      countermeasures. At the same time we'll advance a series of corresponding
      countermeasures of genetic ethical problem. The final aim in the paper is that
      not only some of our opinions will be admitted, but also through learning and
      understanding genetic ethical problem and its origin, the decision-makers and
      investigators in genetics field will be promoted to have more sense of fate and
      responsibility , so that the average public are able to misunderstand less and
      understand more for studying and genetics applying. We all work hard for genetics
      career to make it in healthy and continuing development and give a lot of
      happiness to human beings.

PMID- 18332013
TI  - The effect of elbow position on the range of supination and pronation of the
      forearm.
AB  - A kinematic study was performed to examine the influence of elbow position on the
      range of supination and pronation of the forearm. The ranges of supination and
      pronation were measured in 50 volunteers (25 men and 25 women) using a custom
      designed jig which constrained unwanted and confounding movements of the limb.
      Measurements were taken with the elbow in full extension, 45 degrees flexion, 90
      degrees flexion and full flexion. The data showed a reciprocal relationship
      between the range of supination and the range of pronation of the forearm which
      depended on the degree of elbow flexion. As the elbow is flexed, the maximum
      angle of supination increases while the maximum angle of pronation decreases
      (p<0.001). The converse is true as the elbow is extended (p<0.001).

PMID- 18332014
TI  - Which questionnaire is best? The reliability, validity and ease of use of the
      Patient Evaluation Measure, the Disabilities of the Arm, Shoulder and Hand and
      the Michigan Hand Outcome Measure.
AB  - The Patient Evaluation Measure (PEM), The Michigan Hand Outcome Questionnaire
      (MHQ) and the Disabilities of the Arm, Shoulder and Hand (DASH) score were
      assessed independent of their originators for reliability, construct and
      criterion validity and acceptability, using an ease of use questionnaire. These
      were administered in random order to 100 patients with different hand and wrist
      disorders and with different impairments of movement, pain, sensation and
      strength. The internal consistency of all three questionnaires was very high
      suggesting redundancy in the questions. All questionnaires were reproducible and
      valid for finger and wrist disorders, but less for nerve disorders. All had poor
      construct validity. The PEM was the easiest to understand and complete, taking
      the least time. Correlation between the scales is high and conversion equations
      were calculated. All three are reliable and reproducible patient completed
      questionnaires, but the PEM is the easiest to use. The validity of all is
      suspected for nerve disorders.

PMID- 18332015
TI  - A study of functional outcomes following implantation of a total distal
      radioulnar joint prosthesis.
AB  - This paper reports a long-term follow-up measuring pain, range of motion and
      weight-bearing ability, following implantation of a total distal radioulnar joint
      prosthesis. This prosthesis differs from excision arthroplasties and ulnar head
      replacements by replacing all three components of the distal radioulnar joint,
      viz. the sigmoid notch, the ulnar head and the triangular fibrocartilage. The
      design allows longitudinal migration of the radius throughout pronation and
      supination, as well as load bearing of the wrist. Thirty-one patients receiving
      the prosthesis returned or were interviewed by telephone at a mean of 5.9 (range
      4-9) years. Pronation increased from a mean of 65.5 degrees (range 5-90 degrees )
      to 74 degrees (range 20-90 degrees ) and supination from 53 degrees (range 5-90
      degrees ) to 70 degrees (range 20-90 degrees ) while greatly diminishing and/or
      eliminating pain. Grip increased from a mean of 10 kg (22 lbs) to 24 kg (52 lbs).
      Weight bearing was restored or increased in 29 of 31 patients.

PMID- 18332016
TI  - Keloid formation resulting in acquired syndactyly of an initially normal web
      space following syndactyly release of an adjacent web space.
AB  - We present a case of acquired syndactyly secondary to keloid formation in a
      previously normal web space following release of syndactyly in the adjacent web
      space.

PMID- 18332017
TI  - A practical electrophysiological guide for non-surgical and surgical treatment of
      carpal tunnel syndrome.
AB  - In the present study, we illustrate the use of an electrophysiological
      classification as a guide to the treatment of carpal tunnel syndrome (CTS). A
      total of 113 CTS patients were assessed with symptom severity scores, hand
      functional scores and electrophysiological studies. By setting criteria of
      electrophysiological tests, 179 hands in 113 patients were classified into mild,
      moderate and severe degrees of CTS. Of these, the 41 hands with severe CTS were
      referred for surgery. The 58 hands with moderate CTS and 80 hands with mild CTS
      received conservative treatment. The improvement ratios in the severe group were
      greater than that in the moderate and mild groups, both at 6 months and at 1
      year. Eighteen hands with moderate or mild CTS returned to normal
      electrophysiology with the conservative treatments. No patient recovered to
      normal electrophysiology in the severe group. This electrophysiological
      classification is objective and it may serve as a useful guide for non-surgical
      and surgical treatment of CTS.

PMID- 18332018
TI  - Two to five year follow-up of the LPM ceramic coated proximal interphalangeal
      joint arthroplasty.
AB  - This paper presents a retrospective series of 20 LPM semi-constrained ceramic
      coated cobalt chrome proximal interphalangeal joint arthroplasties performed
      consecutively in 12 patients for arthritis of the proximal interphalangeal joint
      by a single surgeon between 2000 and 2004. Eleven were performed for
      osteoarthritis, four for post-traumatic arthritis and five for rheumatoid
      arthritis. Although 12 joints had an improvement in pain and an increased
      functional arc of movement, six joints required revision surgery for implant
      failure at an average of 19 months, with clinical signs of increasing pain,
      deteriorating motion and radiological signs of implant loosening and subsidence.
      This rate of revision is higher than in published series for other PIP joint
      implants and, therefore, close surveillance of all patients with this prosthesis
      currently in situ is recommended. Use of the prosthesis has ceased in this unit.

PMID- 18332019
TI  - Intractable neurostenalgia of the ulnar nerve abolished by neurolysis 18 years
      after injury.
AB  - A 39 year-old farmer sustained a closed rupture of the left brachial artery,
      which was successfully managed by emergency vein graft repair of the artery.
      Adjacent nerve trunks were seen to be intact, but stretched. Burning pain in the
      distribution of the ulnar nerve started at day seven postoperatively, and
      worsened over the ensuing years. There was no response to membrane stabilising
      drugs, amitryptiline, nor to regional sympatholytic or local anaesthetic blocks.
      Neurolysis of the ulnar nerve, which was densely adherent to the dilated vein
      graft, abolished his pain.

PMID- 18332020
TI  - The clinical features of ulnar polydactyly in a middle eastern population.
AB  - Two clinical forms of ulnar polydactyly are recognised in the literature, viz the
      African and the Caucasian forms. The current study investigated the clinical and
      radiological features of ulnar polydactyly in 94 Saudi patients. The incidence of
      ulnar polydactyly was one in 1000 live births. There were 41 males and 53
      females. Positive family history, syndromal cases, associated hand anomalies,
      polydactyly of the little toe and systemic abnormalities were seen in 11%, 6%,
      5%, 29% and 23% of cases, respectively. There were 50 unilateral (53%) and 44
      bilateral cases (47%). In unilateral cases, the left hand was more commonly
      affected. Using a modified Rayan-Frey classification, the majority of cases were
      classified as Type II (pedunculated polydactyly, 52 (55%) cases) and Type III (a
      functioning and articulating extra digit without complete duplication of the
      metacarpal, 29 (31%) cases). It was concluded that the Saudi clinical
      presentation of ulnar polydactyly is somewhat different epidemiologically and
      lies between the African and Caucasian forms.

PMID- 18332021
TI  - Early experience with the TriMed fragment-specific fracture fixation system in
      intraarticular distal radius fractures.
AB  - This paper reports the results of fixation of intraarticular fractures of the
      distal radius using the TriMed fragment-specific fixation system by surgeons
      early in their experience with the system. A consecutive series of 22 AO types C2
      and C3 fractures in 21 patients were internally fixed with the system.
      Restoration of articular congruity to less than 2 mm was possible in 20
      fractures. At a minimum of 6 months follow-up, mean volar and radial inclination
      were 8 degrees and 25 degrees , respectively, with no loss of reduction. The
      patients had a mean of 50 degrees flexion, 63 degrees extension and a pronation
      supination arc of 149 degrees . The mean subjective Patient Rated Wrist Score was
      20. Our complication rate was comparable to other published series despite long
      operating times. Therefore, we commend the system as a powerful tool to treat
      these difficult fractures but acknowledge the significant learning curve.

PMID- 18332022
TI  - Long term follow-up after finger replantation.
AB  - The aim of this retrospective study was to assess objective and subjective
      aspects of the long-term results of finger replantations and revascularisations.
      Forty patients with 59 successfully replanted or revascularised fingers, who had
      a mean age of 38 years, were followed-up over an average of 3.5 years. The
      assessment included: the profile of the blood flow in the digital arteries of
      replanted fingers with Doppler ultrasound, active range of motion, total grip
      strength, pinch grip, static two-point discrimination test and Semmes-Weinstein
      monofilament testing. The dexterity of the hand was evaluated subjectively with
      the Carlsson's questionnaire and cold intolerance with a modified McCabe's
      questionnaire. Statistical analysis was performed and a statistically significant
      correlation was found between the Carlsson's functional score, active range of
      motion and total grip strength. In 28 fingers (74%), blood flow in the digital
      arteries showed an undisturbed profile, while ten fingers showed mild stenosis or
      impaired microcirculation.

PMID- 18332023
TI  - Primary bone grafting with pedicled flap cover for dorsal combined injuries of
      the digits.
AB  - Twenty digits in 15 patients with dorsal combined tissue loss were treated by
      radical debridement, primary non-vascularised iliac crest bone graft and
      immediate lower abdominal flap cover between 1996 and 2006. The average length of
      the bone grafts was 3.3 (range 2.5-5) cm. No extensor tendon reconstruction was
      carried out. The flaps were divided at 3 weeks without delay. Permissible
      thinning of the flap was done at the time of division of flaps. No secondary
      procedure was done. All patients were retrospectively reviewed and X-rays
      obtained. Radiological union was achieved in 18 of 20 digits. One bone graft was
      removed because of infection. One bridging bone graft united with the distal
      phalanx but had a painless non-union with the proximal phalanx. There were no
      flap complications. Bone graft length resorptions of 20% and 15% occurred in two
      terminal bone grafts. We recommend this protocol as a solution to this
      challenging problem.

PMID- 18332024
TI  - Open reduction and interfragmentary screw fixation for symptomatic nonunion of
      distal phalangeal fractures.
AB  - Although most distal phalangeal fractures can be treated conservatively, there
      exists a subset of patients who are liable to develop symptomatic non-union,
      manifesting as pain and/or instability, and who may benefit from early fracture
      fixation. This group of patients includes those with displaced or comminuted
      fractures of the shaft or neck and those with oblique fractures prone to
      displacement. This paper reviews the use of a cortical miniscrew for fixation of
      fracture non-union in these patients and shows that this is an effective
      treatment modality with minimal morbidity. Fourteen patients with fractures of
      the shaft or neck of the distal phalanx complicated by symptomatic non-union were
      treated by open reduction and interfragmentary screw fixation. All of the
      fractures united at a mean of 4.2 months and all patients regained normal
      function of the finger.

PMID- 18332025
TI  - The surgical management of thumb deformity in cerebral palsy.

PMID- 18332026
TI  - Ewing's sarcoma of the distal phalanx of the little finger.

PMID- 18332027
TI  - A new technique for reduction of flexor tendon avulsions after delayed
      presentation.

PMID- 18332028
TI  - Re: ossifying lipoma of the hand.

PMID- 18332029
TI  - Posterior interosseous nerve palsy caused by a myxoma.

PMID- 18332030
TI  - Re: flexor pollicis longus rupture 25 years after silicone lunate replacement for
      stage IV Kienbock's disease.

PMID- 18332031
TI  - Osteonecrosis and pathological fracture of the metacarpal shaft caused by silk
      sutures.

PMID- 18332032
TI  - A case of brachial amyotrophy mimicking rupture of the flexor digitorum profundus
      tendon.

PMID- 18332033
TI  - Re: intraneural perineurioma of the median nerve. A rare cause of carpal tunnel
      syndrome.

PMID- 18332034
TI  - An alternative 'viewing box' for hand X-rays.

PMID- 18332035
TI  - Dupuytren's disease in an 8 year-old.

PMID- 18332036
TI  - Closed rupture of a flexor tendon of unknown aetiology.

PMID- 18332037
TI  - Spontaneous subperineural haemorrhage causing acute carpal tunnel syndrome.

PMID- 18332038
TI  - Large-scale gene expression pattern analysis, in situ, in Caenorhabditis elegans.
AB  - Observation of gene expression in situ provides a direct connection between the
      genetic information in the genome sequence and the fully determined developmental
      cell lineage of Caenorhabditis elegans. Green Fluorescent Protein (GFP) reporters
      have been fused with many C. elegans genes, in large-scale projects, by
      conventional DNA ligation, PCR stitching, Gateway recombination and
      recombineering. These reporter gene fusions have then been used in C. elegans
      transformation either by microinjection or microprojectile bombardment. So far,
      the developmental distributions of GFP, as driven by the C. elegans DNA to which
      the reporter gene has been attached, have been determined simply from direct
      examination of the transgenic strains by epifluorescence microscopy. Automation
      of GFP expression pattern determination promises improvements in both quality and
      quantity of this data type, facilitating the handling of such expression pattern
      data within computer databases. As with the descriptions of the developmental
      cell lineage and the genome sequence, a complete description of gene expression
      patterns will provide a vital knowledge framework through which a full
      understanding of the development of this animal can emerge.

PMID- 18332039
TI  - Mortality after long-term sickness absence: prospective cohort study.
AB  - BACKGROUND: The study estimated the excess mortality after long-term sickness
      absence (LTSA), and identified socio-demographic and diagnostic risk factors of
      death. METHODS: Prospective cohort study during 1994-2003 in a Norwegian county
      with 256,654 inhabitants aged 16-62 years. A representative sample of 3386
      persons with a spell of sickness absence >8 weeks was compared with the total
      county population with respect to all cause mortality. Comparative mortality
      figures (CMF) for the total sample and standardized mortality rates for
      diagnostic groups were calculated. RESULTS: The CMFs were 1.5 (95% CI 1.1-1.9)
      for the female and 2.0 (95% CI 1.7-2.4) for the male sample. Among women,
      persons' sickness certified with cancer contributed with 43% of all deaths and
      standardized mortality ratios (SMR) was 16.1 (11.2-23.2). The respective figure
      for the men was 27% and SMR was 8.0 (5.7-11.1). SMR for men with mental diagnoses
      was 1.7 (95% CI 1.1-2.9) and for 'other' (respiratory, neurological, digestive)
      1.8 (95% CI 1.3-2.7). Musculoskeletal cases had not elevated SMRs. Cox
      proportional hazard analysis with musculoskeletal cases as reference adjusted for
      age and income showed very high hazard ratios (HR) for cases with cancer
      diagnoses. Among the men, mental and 'other' diagnoses had also HR above unity.
      CONCLUSION: The study verified findings from Finland and the UK of excess
      mortality after LTSA, also when compared with the total population of the same
      age. Among women, cancer cases explained all the excess mortality, whereas other
      cases outside the musculoskeletal group also contributed among men.

PMID- 18332040
TI  - Distinct roles of XRCC4 and Ku80 in non-homologous end-joining of endonuclease-
      and ionizing radiation-induced DNA double-strand breaks.
AB  - Non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSBs) is mediated
      by two protein complexes comprising Ku80/Ku70/DNA-PKcs/Artemis and
      XRCC4/LigaseIV/XLF. Loss of Ku or XRCC4/LigaseIV function compromises the
      rejoining of radiation-induced DSBs and leads to defective V(D)J recombination.
      In this study, we sought to define how XRCC4 and Ku80 affect NHEJ of site
      directed chromosomal DSBs in murine fibroblasts. We employed a recently developed
      reporter system based on the rejoining of I-SceI endonuclease-induced DSBs. We
      found that the frequency of NHEJ was reduced by more than 20-fold in XRCC4-/-
      compared to XRCC4+/+ cells, while a Ku80 knock-out reduced the rejoining
      efficiency by only 1.4-fold. In contrast, lack of either XRCC4 or Ku80 increased
      end degradation and shifted repair towards a mode that used longer terminal
      microhomologies for rejoining. However, both proteins proved to be essential for
      the repair of radiation-induced DSBs. The remarkably different phenotype of XRCC4
      and Ku80-deficient cells with regard to the repair of enzyme-induced DSBs
      mirrors the embryonic lethality of XRCC4 knock-out mice as opposed to the
      viability of the Ku80 knock-out. Thus, I-SceI-induced breaks may resemble DSBs
      arising during normal DNA metabolism and mouse development. The removal of these
      breaks likely has different genetic requirements than the repair of radiation
      induced DSBs.

PMID- 18332041
TI  - Elevated alpha-synuclein mRNA levels in individual UV-laser-microdissected
      dopaminergic substantia nigra neurons in idiopathic Parkinson's disease.
AB  - The presynaptic protein alpha-synuclein is involved in several neurodegenerative
      diseases, including Parkinson's disease (PD). In rare familial forms of PD,
      causal mutations (PARK1) as well as multiplications (PARK4) of the alpha
      synuclein gene have been identified. In sporadic, idiopathic PD, abnormal
      accumulation and deposition of alpha-synuclein might also cause degeneration of
      dopaminergic midbrain neurons, the clinically most relevant neuronal population
      in PD. Thus, cell-specific quantification of alpha-synuclein expression-levels in
      dopaminergic neurons from idiopathic PD patients in comparison to controls would
      provide essential information about contributions of alpha-synuclein to the
      etiology of PD. However, a number of previous studies addressing this question at
      the tissue-level yielded varying results regarding alpha-synuclein expression. To
      increase specificity, we developed a cell-specific approach for mRNA
      quantification that also took into account the important issue of variable RNA
      integrities of the individual human postmortem brain samples. We demonstrate that
      PCR -amplicon size can confound quantitative gene-expression analysis, in
      particular of partly degraded RNA. By combining optimized UV-laser
      microdissection- and quantitative RT-PCR-techniques with suitable PCR assays, we
      detected significantly elevated alpha-synuclein mRNA levels in individual,
      surviving neuromelanin- and tyrosine hydroxylase-positive substantia nigra
      dopaminergic neurons from idiopathic PD brains compared to controls. These
      results strengthen the pathophysiologic role of transcriptional dysregulation of
      the alpha-synuclein gene in sporadic PD.

PMID- 18332042
TI  - A systematic characterization of factors that regulate Drosophila segmentation
      via a bacterial one-hybrid system.
AB  - Specificity data for groups of transcription factors (TFs) in a common regulatory
      network can be used to computationally identify the location of cis-regulatory
      modules in a genome. The primary limitation for this type of analysis is the
      paucity of specificity data that is available for the majority of TFs. We
      describe an omega-based bacterial one-hybrid system that provides a rapid method
      for characterizing DNA-binding specificities on a genome-wide scale. Using this
      system, 35 members of the Drosophila melanogaster segmentation network have been
      characterized, including representative members of all of the major classes of
      DNA-binding domains. A suite of web-based tools was created that uses this
      binding site dataset and phylogenetic comparisons to identify cis-regulatory
      modules throughout the fly genome. These tools allow specificities for any
      combination of factors to be used to perform rapid local or genome-wide searches
      for cis-regulatory modules. The utility of these factor specificities and tools
      is demonstrated on the well-characterized segmentation network. By incorporating
      specificity data on an additional 66 factors that we have characterized, our
      tools utilize approximately 14% of the predicted factors within the fly genome
      and provide an important new community resource for the identification of cis
      regulatory modules.

PMID- 18332043
TI  - Intent-to-treat analysis of the placebo-controlled trial of letrozole for
      extended adjuvant therapy in early breast cancer: NCIC CTG MA.17.
AB  - BACKGROUND: MA.17 evaluated letrozole or placebo after 5 years of tamoxifen and
      showed significant improvement in disease-free survival (DFS) for letrozole
      [hazard ratio (HR) 0.57, P = 0.00008]. The trial was unblinded and placebo
      patients were offered letrozole. PATIENTS AND METHODS: An intent-to-treat
      analysis of all outcomes, before and after unblinding, on the basis of the
      original randomization was carried out. RESULTS: In all, 5187 patients were
      randomly allocated to the study at baseline and, at unblinding, 1579 (66%) of
      2383 placebo patients accepted letrozole. At median follow-up of 64 months (range
      16-95), 399 recurrences or contralateral breast cancers (CLBCs) (164 letrozole
      and 235 placebo) occurred. Four-year DFS was 94.3% (letrozole) and 91.4%
      (placebo) [HR 0.68, 95% confidence interval (CI) 0.55-0.83, P = 0.0001] and
      showed superiority for letrozole in both node-positive and -negative patients.
      Corresponding 4-year distant DFS was 96.3% and 94.9% (HR 0.80, 95% CI 0.62-1.03,
      P = 0.082). Four-year overall survival was 95.1% for both groups. The annual rate
      of CLBC was 0.28% for letrozole and 0.46% for placebo patients (HR 0.61, 95% CI
      0.39-0.97, P = 0.033). CONCLUSIONS: Patients originally randomly assigned to
      receive letrozole within 3 months of stopping tamoxifen did better than placebo
      patients in DFS and CLBC, despite 66% of placebo patients taking letrozole after
      unblinding.

PMID- 18332045
TI  - Phthalate induction of CYP3A4 is dependent on glucocorticoid regulation of PXR
      expression.
AB  - Cytochrome P450 3A4 (CYP3A4) is responsible for oxidative metabolism of more than
      60% of all pharmaceuticals. CYP3A4 is inducible by xenobiotics that activate
      pregnane X receptor (PXR), and enhanced CYP3A4 activity has been implicated in
      adverse drug interactions. Recent evidence suggest that the widely used
      plasticizer, di-2-ethylhexyl phthalate (DEHP), and its primary metabolite mono-2
      ethylhexyl phthalate (MEHP) may act as agonists for PXR. Hospital patients are
      uniquely exposed to high levels of DEHP as well as being administered
      glucocorticoids. Glucocorticoids positively regulate PXR expression in a
      glucocorticoid receptor (GR)-mediated mechanism. We suggest that the magnitude of
      CYP3A4 induction by phthalates is dependent on the expression of PXR and may be
      significantly higher in the presence of glucocorticoids. DEHP and MEHP induced
      PXR-mediated transcription of the CYP3A4 promoter in a dose-dependent fashion.
      Coexposure to phthalates and dexamethasone (Dex) resulted in enhanced CYP3A4
      promoter activity; furthermore, this induction was abrogated by both the GR
      antagonist RU486 and GR small interfering ribonucleic acid. Dex induced PXR
      protein expression in human hepatocytes and a liver-derived rat cell line. CYP3A4
      protein was highly induced by Dex and DEHP coadministration in human hepatocyte
      cultures. Finally, enhanced 6beta-hydroxytestosterone formation in Dex and
      phthalate cotreated human hepatocytes confirmed CYP3A4 enzyme induction.
      Concomitant exposure to glucocorticoids and phthalates resulting in enhanced
      metabolic activity of CYP3A4 may play a role in altered efficacy of
      pharmaceutical agents. Understanding the role of glucocorticoid regulation of PXR
      as a key determinant in the magnitude of CYP3A4 induction by xenobiotics may
      provide insight into adverse drug effects in a sensitive population.

PMID- 18332044
TI  - Heme-oxygenase 1 gene expression is a marker for hexavalent chromium-induced
      stress and toxicity in human dermal fibroblasts.
AB  - Several adverse health effects, including irritant and allergic contact
      dermatitis, have been reported among workers who are occupationally exposed to
      chromium-containing compounds. Human dermal fibroblasts were used as an in vitro
      experimental model to study the potential mechanisms underlying hexavalent
      chromium [Cr(VI)]-induced dermal toxicity. Exposure of the fibroblasts to 5
      microM Cr(VI) (LC50 for a 24-h exposure period) followed by microarray analysis
      of the gene expression profile revealed overexpression of several genes including
      those involved in cell stress response. The cellular level of glutathione, the
      major antioxidant molecule present in the cells, was significantly lower in the
      Cr(VI)-treated cells compared to the corresponding control cells. The Cr(VI)
      induced overexpression of heme-oxygenase 1 messenger RNA (HO-1) in the
      fibroblasts was significantly blocked by actinomycin D and by inhibitors of MAP
      kinase pathways. The Cr(VI)-induced cytotoxicity and the overexpression of the HO
      1 gene were dependent on the glutathione level of the fibroblasts. Buthionine
      sulfoximine-mediated GSH depletion resulted in enhanced Cr(VI) cytotoxicity and
      further overexpression of the HO-1 gene. On the other hand, elevated cellular
      levels of glutathione resulting from pretreating the cells with GSH significantly
      protected the cells against the Cr(VI)-induced cytotoxicity and blocked the HO-1
      gene's overexpression. Pretreating the fibroblasts with N-acetyl cysteine also
      significantly reduced the Cr(VI)-induced cytotoxicity and overexpression of the
      HO-1 gene. In conclusion, depletion of GSH leading to cellular stress is a major
      mechanism responsible for Cr(VI)-induced cytotoxicity. Furthermore, the
      expression level of HO-1 gene is a marker for Cr(VI)-induced cell stress leading
      to cytotoxicity.

PMID- 18332046
TI  - A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate
      cancer patients.
AB  - Both genetic variants and messenger RNA (mRNA) expression of DNA repair and tumor
      suppressor genes have been investigated as molecular markers for therapy outcome.
      However, the phenotypic impact of genetic variants often remained unclear, thus
      the rationale of their use in risk prediction may be limited. We therefore
      analyzed genetic variants together with anthropometric and lifestyle factors to
      see how these affect mRNA levels of ERCC1, MDM2 and TP53 in primary blood
      lymphocytes. mRNA expression was measured in 376 prostate cancer patients by
      quantitative real-time polymerase chain reaction after reverse transcription, and
      ERCC1 rs11615 T>C, ERCC1 rs3212986 C>A, MDM2 rs2279744 T>G and TP53 rs17878362
      (p53PIN3) polymorphisms were determined. Considerable interindividual differences
      in mRNA expression were found (coefficients of variation: ERCC1, 45%; MDM2, 43%
      and TP53, 35%). ERCC1 expression was positively correlated with plasma levels of
      beta-carotene (P = 0.03) and negatively correlated with canthaxanthin (P = 0.02)
      and lutein (P = 0.02). Overall, the polymorphisms affected mRNA expression only
      weakly. Carriers of a distinct ERCC1 haplotype (CC) showed, however,
      significantly lower expression values than non-carriers (P = 0.001). Applying
      logistic regression, we found that CC haplotype carriers had a 1.69-fold
      increased odds ratio (95% confidence interval: 1.06-2.71) for reduced ERCC1 mRNA
      levels. This low ERCC1 expression might be associated with reduced DNA repair and
      better therapy response. In summary, the association we have found between ERCC1
      genotype and mRNA expression supports recent clinical observations that genetic
      variation in ERCC1 can affect treatment outcome and prognosis. Our study further
      revealed a modulating effect by nutritional factors.

PMID- 18332047
TI  - Genomic analysis suggests higher susceptibility of children to air pollution.
AB  - Differences in biological responses to exposure to hazardous airborne substances
      between children and adults have been reported, suggesting children to be more
      susceptible. Aim of this study was to improve our understanding of differences in
      susceptibility in cancer risk associated with air pollution by comparing genome
      wide gene expression profiles in peripheral blood of children and their parents.
      Gene expression analysis was performed in blood from children and parents living
      in two different regions in the Czech Republic with different levels of air
      pollution. Data were analyzed by two different approaches: one method first
      selected significantly differentially expressed genes and analyzed these gene
      lists for overrepresented biological processes, whereas the other applied the T
      profiler tool to directly perform pathway analyses on the total gene set without
      preselection of significantly modulated gene expressions. In addition, gene
      expressions in both children and adults were investigated for associations with
      micronuclei frequencies. Both analysis approaches returned considerably more
      genes or gene groups and pathways that significantly differed between children
      from both regions than between parents. Very little overlap was observed between
      children and adults. The two most important biological processes or molecular
      functions significantly modulated in children, but not in adults, are nucleosome
      and immune response related. Our study suggests differences between children and
      adults in relation to air pollution exposure at the transcriptome level. The
      findings underline the necessity of implementing environmental health policy
      measures specifically for protecting children's health.

PMID- 18332048
TI  - Excision repair is required for genotoxin-induced mutagenesis in mammalian cells.
AB  - Certain hexavalent chromium [Cr(VI)] compounds are human lung carcinogens.
      Although much is known about Cr-induced DNA damage, very little is known about
      mechanisms of Cr(VI) mutagenesis and the role that DNA repair plays in this
      process. Our goal was to investigate the role of excision repair (ER) pathways in
      Cr(VI)-mediated mutagenesis in mammalian cells. Repair-proficient Chinese hamster
      ovary cells (AA8), nucleotide excision repair (NER)-deficient (UV-5) and base
      excision repair (BER)-inhibited cells were treated with Cr(VI) and monitored for
      forward mutation frequency at the hypoxanthine-guanine phosphoribosyltransferase
      (HPRT) locus. BER was inhibited using methoxyamine hydrochloride (Mx), which
      binds to apurinic/apyrimidinic sites generated during BER. Notably, we found that
      both NER-deficient (UV-5 and UV-41) and BER-inhibited (AA8 + Mx) cells displayed
      attenuated Cr(VI) mutagenesis. To determine whether this was unique to Cr(VI), we
      included the alkylating agent, methylmethane sulfonate (MMS) and ultraviolet (UV)
      radiation (260 nm) in our studies. Similar to Cr(VI), UV-5 cells exhibited a
      marked attenuation of MMS mutagenesis, but were hypermutagenic following UV
      exposure. Moreover, UV-5 cells expressing human xeroderma pigmentosum
      complementation group D displayed similar sensitivity to Cr(VI) and MMS-induced
      mutagenesis as AA8 controls, indicating that the genetic loss of NER was
      responsible for attenuated mutagenesis. Interestingly, Cr(VI)-induced
      clastogenesis was also attenuated in NER-deficient and BER-inhibited cells. Taken
      together, our results suggest that NER and BER are required for Cr(VI) and MMS
      induced genomic instability. We postulate that, in the absence of ER, DNA damage
      is channeled into an error-free system of DNA repair or damage tolerance.

PMID- 18332049
TI  - ABPI/Bioscience Federation 'In vivo sciences in the UK: sustaining the supply of
      skills in the 21st century': fast-tracking a u-turn.

PMID- 18332050
TI  - OCD and anxiety: from afterthought to independence.

PMID- 18332051
TI  - Effectiveness of single dose rifampicin in preventing leprosy in close contacts
      of patients with newly diagnosed leprosy: cluster randomised controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of chemoprophylaxis using a single dose
      of rifampicin to prevent leprosy in close contacts. DESIGN: Single centre, double
      blind, cluster randomised, placebo controlled trial. SETTING: Leprosy control
      programme in two districts of northwest Bangladesh with a population of more than
      four million. PARTICIPANTS: 28,092 close contacts of 1037 patients with newly
      diagnosed leprosy. 21,711 contacts fulfilled the study requirements.
      INTERVENTIONS: A single dose of rifampicin or placebo given to close contacts in
      the second month of starting the index patient's treatment, with follow-up for
      four years. MAIN OUTCOME MEASURE: Development of clinical leprosy. RESULTS:
      18,869 of the 21,711 contacts (86.9%) were followed-up at four years. Ninety one
      of 9452 contacts in the placebo group and 59 of 9417 in the rifampicin group had
      developed leprosy. The overall reduction in incidence of leprosy using a single
      dose of rifampicin in the first two years was 57% (95% confidence interval 33% to
      72%). The groups did not differ between two and four years. The overall number
      needed to treat (NNT) to prevent a single case of leprosy among contacts was 297
      (95% confidence interval 176 to 537). Differences were found between subgroups at
      two years, both in reduction of incidence and in NNT. CONCLUSION: A single dose
      of rifampicin given to contacts of patients with newly diagnosed leprosy is
      effective at preventing the development of clinical leprosy at two years. The
      effect was maintained, but no difference was seen between the placebo and
      rifampicin groups beyond two years. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN61223447 [controlled-trials.com].

PMID- 18332052
TI  - Cluster randomised trial of a targeted multifactorial intervention to prevent
      falls among older people in hospital.
AB  - OBJECTIVE: To determine the efficacy of a targeted multifactorial falls
      prevention programme in elderly care wards with relatively short lengths of stay.
      DESIGN: Cluster randomised trial. SETTING: 24 elderly care wards in 12 hospitals
      in Sydney, Australia. PARTICIPANTS: 3999 patients, mean age 79 years, with a
      median hospital stay of seven days. INTERVENTIONS: A nurse and physiotherapist
      each worked for 25 hours a week for three months in all intervention wards. They
      provided a targeted multifactorial intervention that included a risk assessment
      of falls, staff and patient education, drug review, modification of bedside and
      ward environments, an exercise programme, and alarms for selected patients. MAIN
      OUTCOME MEASURE: Falls during hospital stay. RESULTS: Intervention and control
      wards were similar at baseline for previous rates of falls and individual patient
      characteristics. Overall, 381 falls occurred during the study. No difference was
      found in fall rates during follow-up between intervention and control wards:
      respectively, 9.26 falls per 1000 bed days and 9.20 falls per 1000 bed days
      (P=0.96). The incidence rate ratio adjusted for individual lengths of stay and
      previous fall rates in the ward was 0.96 (95% confidence interval 0.72 to 1.28).
      CONCLUSION: A targeted multifactorial falls prevention programme was not
      effective among older people in hospital wards with relatively short lengths of
      stay. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRNO
      12605000467639.

PMID- 18332053
TI  - Incidence, preventability and consequences of adverse events in older people:
      results of a retrospective case-note review.
AB  - OBJECTIVES: to estimate the extent, preventability and consequences of adverse
      clinical events in elderly and non-elderly patients. DESIGN: a two-stage
      structured, retrospective, patient case-note review. SETTING: a large NHS
      hospital in England. POPULATION: a random sample of 1,006 non-psychiatric
      patients. MAIN OUTCOME MEASURES: proportion of patients with adverse events, the
      proportion of preventable adverse events and the types and consequences of
      adverse events in patients >or=75 and under 75 years old. RESULTS: forty five
      [13.5%; 95% confidence interval (CI) 10-17] of 332 patients >or=75 years and 42
      (6.2%; 95% CI 4-8) of 674 patients <75 years had at least one adverse event.
      There was a significantly raised risk of experiencing an adverse event with
      increasing age [odds ratio (OR) = 1.03 adverse events per year of life, P <
      0.001]. There was no statistically significant difference in preventability of
      adverse events and also in experiencing disability or death as a result of an
      adverse event by age after adjustment for potential confounders. CONCLUSION:
      adverse events are significantly more common in non-psychiatric elderly
      inpatients than younger patients. There is little evidence that adverse events in
      older patients are more preventable and lead to disability or death more
      frequently.

PMID- 18332054
TI  - Addenbrooke's Cognitive Examination-Revised in day-to-day clinical practice.

PMID- 18332055
TI  - Re: Evaluating the impact of the National Service Framework for Older People;
      qualitative science or populist propaganda?

PMID- 18332056
TI  - The Mental Capacity Act: some implications for black and minority ethnic elders.

PMID- 18332057
TI  - Insulin sensitivity and beta-cell function in older Japanese adults without
      diabetes.

PMID- 18332058
TI  - Trypsin, elastase, plasmin and MMP-9 activity in the serum during the human
      ageing process.
AB  - OBJECTIVE: the aim of this work was to define the influence of the ageing process
      on the activity of proteolytic enzymes, such as trypsin, elastase, plasmin and
      active MMP-9 concentration, as well as the inhibitor alpha 1-antitrypsin.
      Moreover, we assessed associations between enzyme activity and selected clinical
      and biochemical parameters. METHODS: healthy normotensive volunteers (n = 60, 30
      women) aged 20-82 years were split into subgroups: young (aged 20-22), middle
      aged (49-52) and elderly (77-82). Serum enzyme activity was assessed using
      fluorometric methods. RESULTS: overall, active MMP-9 concentration and trypsin
      activity decreased with age, and alpha1-antitrypsin concentration and plasmin
      activity increased. Activity of elastase increased with age when compared to the
      young age group. An inverse correlation was identified between MMP-9
      concentration and BMI and a direct correlation found between BMI and elastase,
      plasmin activity and alpha1-antitrypsin concentration. In the middle-aged group,
      glucose correlated directly with trypsin activity and inversely with MMP-9
      concentration. Trypsin activity and MMP-9 concentration correlated inversely with
      cholesterol concentration and plasmin and elastase activity, and the alpha1
      antitrypsin concentration correlated with cholesterol concentration in the
      overall group. CONCLUSIONS: the results confirm the influence of the ageing
      process on the activity of serum proteolytic enzymes. The activity of individual
      proteolytic enzymes in the serum changes with age.

PMID- 18332059
TI  - Association of the arterial access site at angioplasty with transfusion and
      mortality: the M.O.R.T.A.L study (Mortality benefit Of Reduced Transfusion after
      percutaneous coronary intervention via the Arm or Leg).
AB  - BACKGROUND: Bleeding and transfusion after percutaneous coronary intervention
      (PCI) are known predictors of mortality. Transradial arterial access reduces
      bleeding and transfusion related to femoral access complications, although its
      association with mortality is unknown. OBJECTIVE: To determine the association of
      arterial access site (radial or femoral) with transfusion and mortality in
      unselected PCIs. DESIGN, SETTING AND PATIENTS: By data linkage of three
      prospectively collated provincial registries, 38,872 procedures in 32,822
      patients in British Columbia were analysed. The association between access site,
      transfusion and outcomes was assessed by logistic regression, propensity score
      matching and probit regression. MAIN OUTCOME MEASURES: 30-Day and 1-year
      mortality. RESULTS: 1134 (3.5%) patients had at least one blood transfusion.
      Transfused patients had a significantly increased 30-day and 1-year mortality,
      adjusted odds ratio (95% CI) 4.01 (3.08 to 5.22) and 3.58 (2.94 to 4.36),
      respectively. By probit regression the absolute increase in risk of death at 1
      year associated with receiving a transfusion was 6.78%. The number needed to
      treat was 14.74 (prevention of 15 transfusions required to "avoid" one death).
      Radial access halved the transfusion rate. After adjustment for all variables,
      radial access was associated with a significant reduction in 30-day and 1-year
      mortality, odds ratio = 0.71 (95% CI 0.61 to 0.82) and 0.83 (0.71 to 0.98),
      respectively (all p<0.001). CONCLUSIONS: In a registry of all comers to PCI,
      transradial access was associated with a halving of the transfusion rate and a
      reduction in 30-day and 1-year mortality.

PMID- 18332060
TI  - How to cost cardiovascular care.

PMID- 18332061
TI  - Stenting of the right ventricular outflow tract in the symptomatic infant with
      tetralogy of Fallot.
AB  - BACKGROUND: Repair of neonatal tetralogy of Fallot (TOF) has low mortality.
      Debate continues regarding the initial management of cyanotic or duct-dependent
      infants with TOF and adverse risk factors. While repair can and has been
      performed in these patients, it is associated with increased morbidity.
      OBJECTIVE: We review the effectiveness of right ventricular outflow tract (RVOT)
      stenting in the symptomatic young infant with TOF. METHODS: Clinical,
      echocardiographic, angiographic and haemodynamic data were reviewed for nine
      patients who underwent 11 RVOT stenting procedures from October 1994 to August
      2007. RESULTS: The pulmonary valve was deemed unsalvageable in all patients
      (median valve diameter 3.7 mm (range 2.7-4.2), Z-score -6.7 (range -9.7 to -5.4).
      RVOT stenting improved arterial oxygen saturation from a median of 73% (60-85%)
      to 94% (90-98%) (p = 0.008). Median Z-score for the left pulmonary artery
      increased from -4.9 (-7.8 to -2.4) before stent implantation to -1.5 (-4.2 to 
      0.2) (p = 0.02) before surgical repair. Median Z-score for the right pulmonary
      artery increased from -3.7 (-6.8 to -1.9) to -0.8 (-2.5 to 0.1) (p = 0.008).
      Median Nakata index increased from 56 mm(2)/m(2) (21-77) to 150 mm(2)/m(2) (123
      231) (p = 0.008). There were no procedural complications. Six patients have
      undergone successful repair. There were no deaths. CONCLUSIONS: In the
      symptomatic young infant with TOF, stenting of the RVOT provides a safe and
      effective management strategy, improving arterial oxygen saturation and
      encouraging pulmonary artery growth.

PMID- 18332062
TI  - Short- and long-term outcomes following atrial fibrillation in patients with
      acute coronary syndromes with or without ST-segment elevation.
AB  - OBJECTIVE: To assess variables associated with the occurrence of atrial
      fibrillation (AF) and the relation of AF with short- and long-term outcomes and
      with other in-hospital complications in patients with acute coronary syndromes
      (ACS) with and without ST-segment elevation. DESIGN: Pooled database of 120 566
      patients with ST-segment elevation myocardial infarction (STEMI) and non-ST
      segment elevation (NSTE) ACS enrolled in 10 clinical trials. Multivariable
      logistic regression and Cox proportional hazards modelling were used to identify
      factors associated with AF and its relation with clinical outcomes. SETTING: ACS
      complicated by AF. PATIENTS: 120,566 patients with STEMI and NSTE-ACS in 10
      clinical trials. INTERVENTIONS: None evaluated. MAIN OUTCOME MEASURE: Short- and
      long-term mortality. RESULTS: Occurrence of AF was 7.5% in the overall population
      (STEMI 8.0% (n = 84 161); NSTE-ACS = 6.4% (n = 36,405)). Seven-day mortality was
      higher for patients with AF (5.1%) than for those without (1.6%). After adjusting
      for confounders, association of AF with 7-day mortality was present in STEMI
      (hazards ratio (HR) = 1.65; 95% CI 1.44 to 1.90) and NSTE-ACS (HR = 2.30; 95% CI
      1.83 to 2.90; p interaction = 0.015). Risk of long-term mortality (day 8 to 1
      year) was also higher in STEMI (HR = 2.37; 95% CI 1.79 to 3.15) and NSTE-ACS (HR
      = 1.67; 95% CI 1.41 to 1.99). AF had a larger impact in NSTE-ACS on risk of short
      term mortality (p<0.001), stroke (p<0.001), ischaemic stroke (p<0.001) and
      moderate or severe bleeding (p<0.001). CONCLUSIONS: AF is more common in patients
      with STEMI. An association of AF with short- and long-term mortality among
      patients with STEMI and NSTE-ACS was found. Understanding these findings may lead
      to better care of patients with this common arrhythmia.

PMID- 18332063
TI  - The Birmingham Rehabilitation Uptake Maximisation study (BRUM): a randomised
      controlled trial comparing home-based with centre-based cardiac rehabilitation.
AB  - OBJECTIVE: To compare the outcomes of home-based (using the Heart Manual) and
      centre-based cardiac rehabilitation programmes. DESIGN: Randomised controlled
      trial and parallel economic evaluation. SETTING: Predominantly inner-city, multi
      ethnic population in the West Midlands, England. PATIENTS: 525 patients referred
      to four hospitals for cardiac rehabilitation following myocardial infarction or
      coronary revascularisation. INTERVENTIONS: A home-based cardiac rehabilitation
      programme compared with centre-based programmes. MAIN OUTCOME MEASURES: Smoking
      cessation, blood pressure (systolic blood pressure (SBP), diastolic blood
      pressure (DBP)), total cholesterol (TC) and high-density lipoprotein (HDL)
      cholesterol, psychological status (HADS anxiety and depression) and exercise
      capacity (incremental shuttle walking test, ISWT) measured at 12 months. Health
      service resource use, quality of life utility and costs were quantified. RESULTS:
      There were no significant differences in the main outcomes when the home-based
      was compared with the centre-based programme at 12 months. Adjusted mean
      difference (95% CI) for SBP was 1.94 mm Hg (-1.1 to 5.0); DBP 0.42 mm Hg (-1.25
      to 2.1); TC 0.1 mmol/l (-0.05 to 0.24); HADS anxiety -0.02 (-0.69 to 0.65); HADS
      depression -0.35 (-0.95 to 0.25); distance on ISWT -21.5 m (-48.3 to 5.2). The
      relative risk of being a smoker in the home arm was 0.90. The cost per patient to
      the NHS was significantly higher in the home arm at 198 pounds, (95% CI 189 to
      208) compared to 157 pounds (95% CI 139 to 175) in the centre-based arm. However
      when the patients' cost of travel was included, these differences were no longer
      significant. Conclusions A home-based cardiac rehabilitation programme does not
      produce inferior outcomes when compared to traditional centre-based programmes as
      provided in the United Kingdom.

PMID- 18332064
TI  - "And they told two friends...and so on": RJ Reynolds' viral marketing of Eclipse
      and its potential to mislead the public.
AB  - OBJECTIVE: To explore viral marketing strategies for Eclipse cigarettes used by
      the RJ Reynolds Company (Winston-Salem, North Carolina, USA). METHODS: Analysis
      of previously secret tobacco industry documents and multimedia materials.
      RESULTS: The failure of RJ Reynolds' (RJR) 1988 "smokeless" cigarette, Premier,
      was in part due to widespread bad word of mouth about the product's flavour,
      quality and difficulty of use. In 1994 RJR introduced an updated version of
      Premier, the ostensibly "reduced risk" Eclipse cigarette. RJR developed viral
      marketing channels to promote Eclipse using (1) exploratory interviews to
      motivate consumers to spread the word about Eclipse prior to market release, (2)
      promotional videos featuring positive feedback from test group participants to
      portray majority consensus among triers, (3) "Tupperware"-like parties for
      Eclipse where participants received samples to pass around in their social
      circles and (4) the Eclipse website's bulletin board as a forum for potential
      users to discuss the brand in their own words. These strategies targeted the
      brand's likeliest adopters, recruited informal and credible representatives of
      the product unaffiliated with RJR, and controlled the information spread about
      the product. CONCLUSIONS: Viral marketing techniques may be particularly useful
      to promote new tobacco products such as Eclipse that have limited appeal and need
      a highly motivated audience of early adopters and acceptors. Such techniques help
      evade the mass rejection that could follow mass promotion, circumvent marketing
      restrictions, and allow tobacco companies to benefit from health claims made by
      consumers. Cigarette manufacturers must be held accountable for perceived health
      benefits encouraged by all promotional activities including viral marketing.

PMID- 18332065
TI  - Nephron number determines susceptibility to renal mass reduction-induced CKD in
      Lewis and Fisher 344 rats: implications for development of experimentally induced
      chronic allograft nephropathy.
AB  - BACKGROUND: The Fisher 344 (F344) rat kidney transplanted to a Lewis rat
      recipient is a common model of chronic renal allograft nephropathy (CAN);
      however, CAN does not develop when the Lewis kidney is grafted into a F344
      recipient. In this study we investigated whether a difference in nephron
      number/glomerular volume exists between the strains that could contribute to a
      greater susceptibility to development of kidney disease in the F344. METHODS:
      Separate animals, male F344 and Lewis rats, were subjected to either sham surgery
      or right uni-nephrectomy and infarction of 2/3 of the left kidney, to produce a
      5/6 ablation/infarction injury (5/6 A/I). Serial urinary protein excretions were
      measured, a terminal 24-h creatinine clearance was obtained and rats were killed
      11 weeks after surgery and kidneys were harvested for pathology. Glomerular
      volumes were measured in the sham controls of each strain. Glomerular number was
      counted in separate, normal rats of each strain. RESULTS: The normal F344 had
      approximately 30% fewer glomeruli than Lewis rats that were larger in volume. The
      sham F344 had similar creatinine clearance and glomerular structure to the Lewis
      shams, although BP and urine protein excretion were higher. After 5/6 A/I the
      F344 developed more severe proteinuria and structural kidney damage. When
      factored for kidney weight, the F344 rats exhibited a greater compensatory
      hyperfiltration in response to 5/6 A/I, compared to Lewis. CONCLUSIONS: The F344
      strain is more vulnerable to development of progressive kidney damage due to 5/6
      A/I, compared to the Lewis. This is likely due to the lower nephron
      number/greater glomerular volume of the F344 that may also account for the
      greater susceptibility to CAN exhibited by this strain.

PMID- 18332066
TI  - HLA-DQ3 is a probable risk factor for CMV infection in high-risk kidney
      transplant patients.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection in transplant patients with special
      risk factors remains a major hazard. CMV-seronegative recipients with
      seropositive donors have the highest risk of developing acute CMV disease. We
      suggest that the HLA-type may influence the occurrence and the severity of
      primary CMV infection of these recipients and the measurement of the special HLA
      types may be useful in the prediction of acute infection. METHODS: Since 1999
      1213 cadaver kidney transplantations have been performed in our clinic. 163 of
      1213 recipients were CMV-seronegative (13%) and 129 of them received the kidney
      from seropositive donors. All 129 patients received CMV infection prophylaxis. Of
      129 CMV-seronegative patients 49 developed acute CMV infection (38%) during the
      first posttransplant year. CMV infection was diagnosed by CMV antigenemia test
      and serologic measurements (ELISA). The particular HLA-genotypes of the
      recipients were studied before the transplantation. The occurrence and the
      severity of CMV infection was investigated in association with HLA-types.
      RESULTS: We found different acute CMV infection distribution in the careers and
      non-careers of investigated HLA-types: HLA-A2, HLA-B12, HLA-Cw7, HLA-DR6 and HLA
      DR11, but the differences were not significant in these HLA-types (P = 0.26, P =
      0.37, P = 0.83, P = 0.07 and P = 0.37). While investigating HLA-DQ3, we found
      that of 68 DQ3-positive patients 32 (47%), of 61 DQ3-negative patients 17 (28%)
      had acute CMV infection and this difference was found to be significant. This
      result was confirmed by univariate and multivariate Cox Regression (P = 0.001)
      and the appropriate significance level was considered by Bonferroni correction.
      CONCLUSIONS: HLA-DQ3 was found to be an independent predictor of CMV infection.
      Our data suggest that patients positive for HLA-DQ3 are more susceptible to CMV
      infection than a comparable group of patients negative for HLA-DQ3. This result
      was not due to rejection and/or treatment for rejection and was not influenced by
      induction therapy. Although we found more symptomatic infections among DQ3+
      patients the difference was not significant (P = 0.19). Comparing the gender
      proportion among all 1213 kidney recipients and among CMV-seronegative recipients
      we found that the proportion of males is significantly higher among CMV
      seronegative recipients (P < 0.001).

PMID- 18332067
TI  - Comparing the automated versus manual method of needle biopsy for renal histology
      artefacts.

PMID- 18332068
TI  - Somatic mosaicism for a mutation of the COL4A5 gene is a cause of mild phenotype
      male Alport syndrome.
AB  - BACKGROUND: Alport syndrome is the most common form of hereditary nephritis and
      is mainly caused by mutations in the COL4A5 gene, which shows the X-linked form.
      It is well known that some male Alport syndrome cases show a relatively mild
      phenotype, but few molecular investigations have been conducted to clarify the
      mechanism of this phenotype. Methods and results. This report concerns an 8-year
      old male sporadic Alport syndrome patient. While electron microscopy of the
      glomerular basement membrane showed typical findings for Alport syndrome,
      however, the immunohistochemical analysis of the glomerulus showed mosaic
      staining of the type IV collagen alpha 5 chain. The mutational analysis of the
      COL4A5 gene unexpectedly disclosed two peaks at the intron 43 splicing acceptor
      site (c. 3998-2 a/t) with direct sequencing. Restriction enzyme analysis
      demonstrated that the presence of somatic mosaicism was responsible for this
      mutation. mRNA extracted from the urinary sediments was analysed by RT-PCR and
      two PCR fragments were amplified, one consisting of a normal sequence and one
      with skipping of exon 44. CONCLUSIONS: Our findings indicate that somatic
      mosaicism for COL4A5 is responsible for male X-linked Alport syndrome with an
      alpha 5 mosaic staining pattern. Several cases with somatic mosaicism have
      previously been reported, however, this is the first case where the presence of
      this mutation was proved with a comprehensive analysis of genomic DNA, mRNA and
      alpha 5 expression in the tissues. Somatic mosaicism may thus be one of the
      causes of the mild phenotype in Alport syndrome.

PMID- 18332069
TI  - First description of polycystic kidney disease in a Portuguese journal.

PMID- 18332070
TI  - Outcomes of a provincial home haemodialysis programme--a two-year experience:
      establishing benchmarks for programme evaluation.
AB  - INTRODUCTION: The province of British Columbia has the only coordinated
      provincial programme for home-based haemodialysis (HHD) in Canada. The centrally
      coordinated and locally administered programme was initiated in 2002 as a pilot
      project, and was firmly established with secured funding in 2004. HHD programmes
      have reported successful outcomes with respect to patients' well-being,
      haemodynamic stability and improvement of clinical and biochemical parameters in
      small selected groups of patients. METHODS: This report describes the 2-year
      outcomes of a provincial programme, in which more liberal criteria for patient
      selection have been applied, and multiple sites have trained and managed the
      patients over a large geographic area. As a 'newer' modality, it is important to
      review outcomes objectively so as to determine the true value of this home-based
      programme as an alternative to other home-based therapies such as peritoneal
      dialysis. RESULTS: One hundred and five patients who completed training and
      commenced home therapy between April 2004 and March 2006 were followed, for a
      total of 163.23 patient-years (PY). The average age was 52; 71% were male and the
      majority (58%) were Caucasian. Mean biochemical and clinical parameters were all
      within provincial and national target ranges at baseline and at the time of study
      follow-up cessation. Overall, 34 individual patients required hospital admission
      and 95% of the cohort required at least one in-centre run after training was
      completed (0.5 hospital admissions and 11 in-centre run per PY of HHD delivered).
      One- and 2-year technique survivals were 81% and 61% respectively, which were 85%
      and 74% when censored for transplantation. We were unable to demonstrate any
      significant predictors of technique survival using demographic, biochemical or
      other variables. CONCLUSION: This is the first report of HHD programme technique
      survival in a large provincial cohort. The 2-year technique survival of this
      cohort is comparable to reports of technique survival in peritoneal dialysis.
      These data can be used to benchmark programmes, and to foster further research to
      determine factors that may improve HHD technique survival.

PMID- 18332071
TI  - Comparison of tissue plasminogen activator-antibiotic locks with heparin
      antibiotic locks in children with catheter-related bacteraemia.
AB  - BACKGROUND: An accepted pathogenesis of catheter-related bacteraemia (CRB) is the
      seeding of microorganisms from the intraluminal biofilm of central venous
      catheters. Antibiotic locks (ABL) are solutions containing high concentrations of
      antimicrobials with or without anticoagulants that aim to destroy the biofilm.
      METHODS: In this study, two different ABL solutions, tissue plasminogen activator
      (TPA)-based and heparin-based ABL, used in conjunction with systemic antibiotics,
      were prospectively compared in the treatment of CRB. RESULTS: A total of 42
      children on chronic haemodialysis with 11,016 catheter-days were observed for
      signs and symptoms of CRB over a period of 10 months. Twenty-four CRBs were
      diagnosed in 18 children (2.2 CRB/1000 catheter-days) and were treated with the
      protocol. Symptoms of CRB resolved in 83% within 48 h of treatment. None of the
      infected catheters required early emergent exchange or removal for poorly
      controlled CRB. Six children had recurrence of CRB within 6 weeks, of which four
      required catheter exchange. There was no specific microorganism or type of CRB
      that predisposed to higher recurrence rates. The mean infection-free survival of
      the catheters following TPA-ABL treatment was shorter than that following heparin
      ABL treatment, but was not statistically significant by the log-rank test (126.8
      +/- 81.6 days versus 154.5 +/- 70.4 days). CONCLUSION: Both TPA-ABL and heparin
      ABL used in conjunction with systemic antibiotics can effectively clear CRB
      without significant late recurrence at 6 weeks. Early use of ABL for management
      of CRB can potentially decrease the need for catheter removal, thus salvaging
      vascular access sites.

PMID- 18332072
TI  - A prospective national study of acute fatty liver of pregnancy in the UK.
AB  - OBJECTIVES: To identify a national, population-based cohort of women with acute
      fatty liver of pregnancy (AFLP), to evaluate proposed diagnostic criteria and to
      document accurately the incidence, management and outcomes of the condition.
      SUBJECTS AND METHODS: This was a population-based descriptive study using the UK
      Obstetric Surveillance System, carried out in all 229 hospitals with consultant
      led maternity units in the UK. The participants comprised 57 women in the UK
      diagnosed with AFLP between February 2005 and August 2006 in an estimated cohort
      of 1 132 964 maternities (women delivering). RESULTS: The estimated incidence of
      AFLP was 5.0 cases per 100 000 maternities (95% CI 3.8 to 6.5 per 100,000). Fifty
      five cases (90%) were confirmed by diagnostic criteria and clinical assessment,
      two (3%) by clinical assessment alone, representing 97% agreement (kappa
      statistic = 0.78). 18% of women had twin pregnancies and 20% were underweight
      (body mass index (BMI) <20). 60% of women were admitted to intensive care and 15%
      to a specialist liver unit. One woman received a liver transplant. One woman died
      (case fatality rate 1.8%, 95% CI 0% to 9.4%). There were seven deaths among 67
      infants (perinatal mortality rate 104 per 1000 births, 95% CI 43 to 203).
      CONCLUSIONS: The largest population-based cohort of women with AFLP to date has
      been identified. Diagnostic criteria previously proposed agree substantially with
      clinical diagnosis. The incidence estimate from this study is lower than
      documented by earlier hospital-based studies, but maternal and neonatal outcomes
      are better than previously reported, possibly related to improved ascertainment.
      Women with twin pregnancies appear to be at higher risk, but further studies are
      needed to investigate the risk associated with low BMI.

PMID- 18332073
TI  - Neurons in the fusiform gyrus are fewer and smaller in autism.
AB  - Abnormalities in face perception are a core feature of social disabilities in
      autism. Recent functional magnetic resonance imaging studies showed that patients
      with autism could perform face perception tasks. However, the fusiform gyrus (FG)
      and other cortical regions supporting face processing in controls are hypoactive
      in patients with autism. The neurobiological basis of this phenomenon is unknown.
      Here, we tested the hypothesis that the FG shows neuropathological alterations in
      autism, namely alterations in neuron density, total neuron number and mean
      perikaryal volume. We investigated the FG (analysing separately layers II, III,
      IV, V and VI), in seven post-mortem brains from patients with autism and 10
      controls for volume, neuron density, total neuron number and mean perikaryal
      volume with high-precision design-based stereology. To determine whether these
      results were specific for the FG, the same analyses were also performed in the
      primary visual cortex and in the cortical grey matter as a whole. Compared to
      controls, patients with autism showed significant reductions in neuron densities
      in layer III, total neuron numbers in layers III, V and VI, and mean perikaryal
      volumes of neurons in layers V and VI in the FG. None of these alterations were
      found in the primary visual cortex or in the whole cerebral cortex. Although
      based on a relatively small sample of post-mortem brains from patients with
      autism and controls, the results of the present study may provide important
      insight about the cellular basis of abnormalities in face perception in autism.

PMID- 18332074
TI  - Amino acid cerebrospinal fluid/plasma ratios in children: influence of age,
      gender, and antiepileptic medication.
AB  - OBJECTIVE: The purpose of this work was to investigate the influence of age,
      gender, and antiepileptic therapy on amino acid cerebrospinal fluid/plasma ratios
      in children. PATIENTS AND METHODS: Concentrations of 17 amino acids measured by
      ion-exchange chromatography with ninhydrin detection in plasma and cerebrospinal
      fluid from 68 patients with neurologic diseases were used to calculate their
      cerebrospinal fluid/plasma ratios (70 measurements; 28 female patients [29
      punctures] and 40 male patients [41 punctures]). Age dependence and the effects
      of gender and antiepileptic medication on amino acid cerebrospinal fluid/plasma
      ratios were investigated by linear multiple regression analysis, and
      nonstandardized predicted mean values for 2 age groups were calculated (cutoff: 3
      years old). RESULTS: The cerebrospinal fluid/plasma ratios ranged between 0.02
      for glycine and 0.93 for glutamine. Age had a significant influence on
      cerebrospinal fluid/plasma ratios for valine, isoleucine, leucine, and tyrosine,
      with higher ratios in younger children. Gender had a significant influence only
      on the glutamine cerebrospinal fluid/plasma ratio (female patients had lower
      ratios). Cerebrospinal fluid/plasma ratios of glutamine and tyrosine were
      significantly elevated by valproate therapy and those of serine, asparagine,
      glutamine, valine, methionine, and phenylalanine by phenobarbital therapy. No
      significant influence of age, gender, and antiepileptic drugs was detectable on
      cerebrospinal fluid/plasma ratios of threonine, proline, glycine, alanine,
      histidine, ornithine, lysine, and arginine. CONCLUSIONS: Cerebrospinal
      fluid/plasma ratios, especially for essential neutral amino acids and for serine,
      asparagine, and glutamine were influenced to different degrees by age, gender,
      and antiepileptic therapy.

PMID- 18332075
TI  - Randomized, double-blind, placebo-controlled trial of probiotics for primary
      prevention: no clinical effects of Lactobacillus GG supplementation.
AB  - BACKGROUND: The value of probiotics for primary prevention is controversial.
      Published trials vary considerably in study design and the applied probiotics,
      thereby limiting comparability of the results. OBJECTIVE: The purpose of this
      trial was to study the preventive effect of the probiotic Lactobacillus GG on the
      development of atopic dermatitis. METHODS: In a double-blind, placebo-controlled
      prospective trial, 105 pregnant women from families with > or = 1 member (mother,
      father, or child) with an atopic disease were randomly assigned to receive either
      the probiotic Lactobacillus GG (American Type Culture Collection 53103; 5 x 10(9)
      colony-forming units of Lactobacillus GG twice daily) or placebo. Ninety-four
      families (89.5%) completed the trial. The supplementation period started 4 to 6
      weeks before expected delivery, followed by a postnatal period of 6 months. The
      primary end point was the occurrence of atopic dermatitis at the age of 2 years.
      Secondary outcomes were severity of atopic dermatitis, recurrent episodes of
      wheezing bronchitis, and allergic sensitization at the age of 2 years. RESULTS:
      Atopic dermatitis was diagnosed in 14 (28%) of 50 in the Lactobacillus GG group
      and in 12 (27.3%) of 44 in the placebo group. The risk of atopic dermatitis in
      children on probiotics relative to placebo was 0.96 (confidence interval 0.38
      2.33). Severity of atopic dermatitis was comparable between the 2 groups.
      Notably, children with recurrent (> or = 5) episodes of wheezing bronchitis were
      more frequent in the Lactobacillus GG group (26%; n = 13), as compared with the
      placebo group (9.1%; n = 4). No difference was observed between both groups in
      total immunoglobulin E concentrations or numbers of specific sensitization to
      inhalant allergens. CONCLUSIONS: Supplementation with Lactobacillus GG during
      pregnancy and early infancy neither reduced the incidence of atopic dermatitis
      nor altered the severity of atopic dermatitis in affected children but was
      associated with an increased rate of recurrent episodes of wheezing bronchitis.
      Therefore, Lactobacillus GG cannot be generally recommended for primary
      prevention.

PMID- 18332076
TI  - Long-term safety and efficacy results of once-daily emtricitabine-based highly
      active antiretroviral therapy regimens in human immunodeficiency virus-infected
      pediatric subjects.
AB  - OBJECTIVES: The purpose of this work was to obtain long-term safety and efficacy
      data for antiretroviral regimens containing emtricitabine in HIV-infected
      pediatric subjects and confirm that a pediatric dose of 6 mg/kg once daily would
      provide steady-state emtricitabine concentrations comparable to those observed in
      adults given 200 mg of emtricitabine once daily. PATIENTS AND METHODS: HIV
      infected subjects between 3 months and 16 years of age were enrolled, including
      71 antiretroviral-naive subjects and 45 antiretroviral-experienced subjects.
      Naive subjects received emtricitabine plus stavudine plus lopinavir or ritonavir.
      Experienced subjects replaced the lamivudine in their existing regimens with
      emtricitabine. Tolerance, safety, disease progression, and virologic and
      immunologic responses were evaluated. RESULTS: The Kaplan-Meier probability of
      persistent virologic response in the intent-to-treat population through week 164
      at < or = 400 copies per mL and < or = 50 copies per mL was 74% and 62%,
      respectively. Three subjects (3%) discontinued the study for adverse events, 8
      (7%) for virologic failure, and 1 died through a median follow-up of 164 weeks.
      The annualized incidence rate of grade 3 to 4 adverse events and grade 3 to 4
      laboratory abnormalities was 6% and 3%, respectively. The annualized incidence
      rate of serious adverse events was 9%, with 1% attributed as related to
      emtricitabine. Genotypic analysis showed the emergence of the M184V mutation in 4
      of the 15 subjects who experienced virologic failure through week 164.
      Pharmacokinetic evaluation demonstrated plasma drug exposures in these children
      comparable to adults receiving the approved dose of 200 mg once daily.
      CONCLUSIONS: These results demonstrate the safety and efficacy of emtricitabine
      in pediatric patients. They also support that the safety and efficacy profile of
      emtricitabine in children is similar to that demonstrated in adults.

PMID- 18332077
TI  - The O-linked glycosylation of secretory/shed MUC1 from an advanced breast cancer
      patient's serum.
AB  - MUC1 is a high molecular weight glycoprotein that is overexpressed in breast
      cancer. Aberrant O-linked glycosylation of MUC1 in cancer has been implicated in
      disease progression. We investigated the O-linked glycosylation of MUC1 purified
      from the serum of an advanced breast cancer patient. O-Glycans were released by
      hydrazinolysis and analyzed by liquid chromatography-electrospray ionization-mass
      spectrometry and by high performance liquid chromatography coupled with
      sequential exoglycosidase digestions. Core 1 type glycans (83%) dominated the
      profile which also confirmed high levels of sialylation: 80% of the glycans were
      mono-, di- or trisialylated. Core 2 type structures contributed approximately 17%
      of the assigned glycans and the oncofoetal Thomsen-Friedenreich (TF) antigen
      (Galbeta1-3GalNAc) accounted for 14% of the total glycans. Interestingly, two
      core 1 type glycans were identified that had sialic acid alpha2-8 linked to
      sialylated core 1 type structures (9% of the total glycan pool). This is the
      first O-glycan analysis of MUC1 from the serum of a breast cancer patient; the
      results suggest that amongst the cell lines commonly used to express recombinant
      MUC1 the T47D cell line processes glycans that are most similar to patient
      derived material.

PMID- 18332078
TI  - Comparison of immortalized Fa2N-4 cells and human hepatocytes as in vitro models
      for cytochrome P450 induction.
AB  - Fa2N-4 cells have been proposed as a tool to identify CYP3A4 inducers. To
      evaluate whether Fa2N-4 cells are a reliable surrogate for cryopreserved human
      hepatocytes, we assessed the basal mRNA expression of 64 drug disposition genes
      in Fa2N-4 cells. Significant differences were found in the expression of major
      drug-metabolizing enzymes, nuclear receptors, and transporters between both cell
      types. Importantly, the expression of constitutive androstane receptor (CAR) and
      several hepatic uptake transporters was significantly lower (>50-fold) in Fa2N-4
      cells, whereas the expression of pregnane X-receptor (PXR) and aryl hydrocarbon
      receptor (AhR) was similar between Fa2N-4 cells and human hepatocytes. By using
      an optimized induction assay for Fa2N-4 cells, CYP3A4 induction by rifampicin,
      the prototypical PXR activator, increased from 1.5- to 7-fold at the level of
      functional activity. With nine selected compounds, which are known inducers of
      CYP3A4 either via activation of PXR, CAR, or both, we evaluated CYP3A4 and CYP2B6
      mRNA induction using Fa2N-4 cells and human hepatocytes. No response was observed
      in Fa2N-4 cells treated with the selective CAR activators 6-(4
      chlorophenyl)imidazo[2,1-b][1,3]-thiazole-5-carbaldehyde O-(3,4
      dichlorobenzyl)oxime and artemisinin. CYP3A4 and CYP2B6 induction in Fa2N-4 cells
      were also low for phenytoin, phenobarbital, and efavirenz, which are dual
      activators of PXR/CAR. This finding was in agreement with the lack of expression
      of CAR. The EC(50) value for rifampicin-mediated CYP3A4 induction was 10-fold
      higher than that in human hepatocytes. This result could be attributed to the low
      expression of hepatic organic anion-transporting polypeptides OATP1B1 and OATP1B3
      in Fa2N-4 cells. In summary, our findings identify limitations of Fa2N-4 cells as
      a predictive induction model.

PMID- 18332079
TI  - Hepatic uptake and excretion of (-)-N-{2-[(R)-3-(6,7-dimethoxy-1,2,3,4
      tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a
      novel if channel inhibitor, in rats and humans.
AB  - (-)-N-{2-[(R)-3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-2
      carbonyl)piperidino]ethyl}-4-fluorobenzamide (YM758), a novel "funny" If current
      channel (If channel) inhibitor, is being developed as a treatment for stable
      angina and atrial fibrillation. The hepatic uptake/excretion of YM758 was
      clarified using transporter-expressing mammalian cells and hepatocytes mainly in
      humans and partly in rats. cDNA-expressing human embryonic kidney 293 cells were
      used to determine that YM758 was greatly taken up via organic anion-transporting
      polypeptide (OATP) 1B1 and slightly via human organic cation transporter (hOCT)
      1/rat organic cation transporter 1 but not via OATP1B3. In addition, the uptake
      of 17beta-estradiol-d-17beta-glucuronide via OATP1B1 was inhibited in the
      presence of YM758, whereas that via OATP1B3 was not. In contrast, time-dependent
      uptake of YM758 into rat/human hepatocytes at 37 degrees C was observed, as was
      concentration-dependent uptake into human hepatocytes (K(m) value of 87.9
      microM). This saturable uptake of YM758 into human hepatocytes was inhibited in
      the presence of quinidine (an inhibitor for OATP1B1) but not cimetidine (an
      inhibitor for the hOCT family). Moreover, the permeation clearance ratios for the
      transcellular transport of YM758 across multidrug resistance (MDR) 1-expressing
      LLC-PK1 cells were extensively higher than those across LLC-PK1 cells, which
      indicate that MDR1-mediated transport is one of the possible pathways through
      which YM758 may be excreted into the bile. These results indicate that YM758 is
      taken up into hepatocytes mainly via OATP1B1, but not via hOCT1, and is excreted
      into the bile via MDR1 in humans; however, passive diffusion or an unknown
      uptake/excretion mechanism could be at work in the hepatocytes. This study is the
      first to clarify the saturable hepatic uptake and/or the excretion mechanism by
      the If channel inhibitor.

PMID- 18332080
TI  - Comparison of the bioactivation potential of the antidepressant and hepatotoxin
      nefazodone with aripiprazole, a structural analog and marketed drug.
AB  - In vitro metabolism/bioactivation of structurally related central nervous system
      agents nefazodone (hepatotoxin) and aripiprazole (nonhepatotoxin) were undertaken
      in human liver microsomes in an attempt to understand the differences in
      toxicological profile. NADPH-supplemented microsomal incubations of nefazodone
      and glutathione generated conjugates derived from addition of thiol to quinonoid
      intermediates. Inclusion of cyanide afforded cyano conjugates to iminium ions
      derived from alpha-carbon oxidation of the piperazine ring in nefazodone and
      downstream metabolites. Although the arylpiperazine motif in aripiprazole did not
      succumb to bioactivation, the dihydroquinolinone group was bioactivated via an
      intermediate monohydroxy metabolite to a reactive species, which was trapped by
      glutathione. Studies with synthetic dehydroaripiprazole metabolite revealed an
      analogous glutathione conjugate with molecular weight 2 Da lower. Based on the
      proposed structure of the glutathione conjugate(s), a bioactivation sequence
      involving aromatic ortho-or para-hydroxylation on the quinolinone followed by
      oxidation to a quinone-imine was proposed. P4503A4 inactivation studies in
      microsomes indicated that, unlike nefazodone, aripiprazole was not a time- and
      concentration-dependent inactivator of the enzyme. Overall, these studies
      reinforce the notion that not all drugs that are bioactivated in vitro elicit a
      toxicological response in vivo. A likely explanation for the markedly improved
      safety profile of aripiprazole (versus nefazodone) despite the accompanying
      bioactivation liability is the vastly improved pharmacokinetics (enhanced oral
      bioavailability, longer elimination half-life) due to reduced P4503A4-mediated
      metabolism/bioactivation, which result in a lower daily dose (5-20 mg/day)
      compared with nefazodone (200-400 mg/day). This attribute probably reduces the
      total body burden to reactive metabolite exposure and may not exceed a threshold
      needed for toxicity.

PMID- 18332081
TI  - Characterization of cytochrome P450 protein expression along the entire length of
      the intestine of male and female rats.
AB  - Intestinal cytochrome P450 (P450) proteins play an important role in the
      biotransformation of drugs and may significantly limit their oral absorption and
      bioavailability. Therefore, we have investigated the amount of P450 proteins via
      Western blot analysis along the entire intestine of male and female rats. Despite
      of the use of an inbred rat strain, controlled housing conditions for the
      animals, and a timed sample preparation, high interindividual differences in the
      expression of all P450 proteins was observed. CYP3A (135-243 fmol/mg of protein)
      and CYP2B1 (107-645 fmol/mg of protein) were the most abundant P450 isoforms in
      the duodenum and jejunum of rat intestine but were present in neither the ileum
      nor the colon. Compared with CYP2B1 and CYP3A, CYP2D1 (25-71 fmol/mg of protein)
      and CYP2C6 (3-10 fmol/mg of protein) were only expressed in minor amounts.
      CYP2C11 could not be identified in the entire rat intestine. In conclusion, this
      is the first systematic evaluation and quantification of the expression of P450
      proteins along the entire length of the intestine in both male and female rats.
      These data will provide a basis for a better understanding of the extent of
      intestinal metabolism along the gastrointestinal tract.

PMID- 18332082
TI  - Identification and characterization of potent CYP2B6 inhibitors in
      Woohwangcheongsimwon suspension, an herbal preparation used in the treatment and
      prevention of apoplexy in Korea and China.
AB  - Woohwangcheongsimwon is a traditional medicine for treating hypertension,
      arteriosclerosis, coma, and stroke in China and Korea. To assess potential
      interactions of herb and drug metabolism, commercially available
      Woohwangcheongsimwon suspensions were examined for their potential to inhibit the
      activity of nine human cytochrome P450 enzymes. The Woohwangcheongsimwon
      suspensions showed strong inhibition of CYP2B6 activity. To identify individual
      constituents with inhibitory activity, the suspension was partitioned using
      hexane, ethyl acetate, and dichloromethane, and each fraction was tested for its
      inhibitory effect on CYP2B6-catalyzed bupropion hydroxylation. The hexane
      fraction possessed inhibitory activity, and gas chromatography/mass spectrometry
      analysis identified borneol and isoborneol as major constituents of the hexane
      fraction. These two terpenoids moderately inhibited CYP2B6-catalyzed bupropion
      hydroxylase activity in a competitive manner, with K(i) values of 9.5 and 5.9
      microM, respectively, as well as efavirenz 8-hydroxylase activity, with K(i)
      values of 22 and 26 microM, respectively. Additionally, reconstituted mixtures of
      borneol and isoborneol, at the same concentrations as in the Woohwangcheongsimwon
      suspension, had comparable potency in inhibiting bupropion hydroxylation. These
      in vitro data indicate that Woohwangcheongsimwon preparations contain
      constituents that can potently inhibit the activity of CYP2B6 and suggest that
      these preparations should be examined for potential pharmacokinetic drug
      interactions in vivo.

PMID- 18332083
TI  - ATF5 is a highly abundant liver-enriched transcription factor that cooperates
      with constitutive androstane receptor in the transactivation of CYP2B6:
      implications in hepatic stress responses.
AB  - Activating transcription factor (ATF) 5 is a member of the ATF/cAMP response
      element-binding protein family, which has been associated with differentiation,
      proliferation, and survival in several tissues and cell types. However, its role
      in the liver has not yet been investigated. We show herein that ATF5 is a highly
      abundant liver-enriched transcription factor (LETF) whose expression declines in
      correlation with the level of dedifferentiation in cultured human hepatocytes and
      cell lines. Re-expression of ATF5 in human HepG2 cells by adenoviral transduction
      resulted in a marked selective up-regulation of CYP2B6. Moreover, adenoviral
      cotransfection of ATF5 and constitutive androstane receptor (CAR) caused an
      additive increase in CYP2B6 mRNA. These results were confirmed in cultured human
      hepatocytes, where the cooperation of ATF5 and CAR not only increased CYP2B6
      basal expression but also enhanced the induced levels after phenobarbital or 6-(4
      chloropheny-l)-imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4
      dichlorobenzyl)oxime (CITCO). Comparative sequence analysis of ATF5 and ATF4, its
      closest homolog, showed a large conservation of the mRNA 5'-untranslated region
      organization, suggesting that ATF5 might be up-regulated by stress responses
      through a very similar translational mechanism. To investigate this possibility,
      we induced endoplasmic reticulum stress by means of amino acid limitation or
      selective chemicals, and assessed the time course response of ATF5 and CYP2B6. We
      found a post-transcriptional up-regulation of ATF5 and a parallel induction of
      CYP2B6 mRNA. Our findings uncover a new LETF coupled to the differentiated
      hepatic phenotype that cooperates with CAR in the regulation of drug-metabolizing
      CYP2B6 in the liver. Moreover, ATF5 and its target gene CYP2B6 are induced under
      different stress conditions, suggesting a new potential mechanism to adapt
      hepatic cytochrome P450 expression to diverse endobiotic/xenobiotic harmful
      stress.

PMID- 18332084
TI  - Aldehyde oxidase-catalyzed metabolism of N1-methylnicotinamide in vivo and in
      vitro in chimeric mice with humanized liver.
AB  - Aldehyde oxidase-mediated oxidation of N(1)-methylnicotinamide to N(1)-methyl-2
      pyridine-5-carboxamide (2-PY) and N(1)-methyl-4-pyridone-5-carboxamide (4-PY) in
      chimeric mice constructed by transplanting human hepatocytes into urokinase-type
      plasminogen activator-transgenic severe combined immunodeficient mice was
      examined in vivo and in vitro. The activity in liver cytosol of chimeric mice
      with a high replacement index was approximately 4-fold higher than that in
      control mice. Furthermore, the oxidation products in control mice were 2-PY and 4
      PY, whereas, in chimeric mice, the major product was 2-PY, as in humans. The
      aldehyde oxidase in chimeric mouse liver was confirmed to be of human type by
      immunoblotting analysis. The ratio of pyridones (2-PY/4-PY) excreted in the urine
      of chimeric mice was closer to that of humans than to that of control mice. Thus,
      the aldehyde oxidase in chimeric mice has human-type functional characteristics.

PMID- 18332085
TI  - P-glycoprotein contributes to the blood-brain, but not blood-cerebrospinal fluid,
      barrier in a spontaneous canine p-glycoprotein knockout model.
AB  - P-glycoprotein is considered to be a major factor impeding effective drug therapy
      for many diseases of the central nervous system (CNS). Thus, efforts are being
      made to gain a better understanding of P-glycoprotein's role in drug distribution
      to brain parenchyma and cerebrospinal fluid (CSF). The goal of this study was to
      validate and introduce a novel P-glycoprotein-deficient (ABCB1-1Delta) canine
      model for studying P-glycoprotein-mediated effects of drug distribution to brain
      tissue and CSF. CSF concentrations of drug are often used to correlate efficacy
      of CNS drug therapy as a surrogate for determining drug concentration in brain
      tissue. A secondary goal of this study was to investigate the validity of using
      CSF concentrations of P-glycoprotein substrates to predict brain tissue
      concentrations. Loperamide, an opioid that is excluded from the brain by P
      glycoprotein, was used to confirm a P-glycoprotein-null phenotype in the dog
      model. ABCB1-1Delta dogs experienced CNS depression following loperamide
      administration, whereas ABCB1 wild-type dogs experienced no CNS depression. In
      summary, we have validated a novel P-glycoprotein-deficient canine model and have
      used the model to investigate transport of the P-glycoprotein substrate (99m)Tc
      sestamibi at the blood-brain barrier and blood-CSF barrier.

PMID- 18332086
TI  - Intestinal human colon adenocarcinoma cell line LS180 is an excellent model to
      study pregnane X receptor, but not constitutive androstane receptor, mediated
      CYP3A4 and multidrug resistance transporter 1 induction: studies with anti-human
      immunodeficiency virus protease inhibitors.
AB  - Lack of an established cell line model to study induction of cytochromes P450
      (P450s) and drug transporters poses a challenge in predicting in vivo drug-drug
      interactions. Although not well characterized, LS180 cells could be an excellent
      cell line to study induction of P450s and transporters because they express
      pregnane X receptor (PXR). Therefore, as part of a larger study of in vitro to in
      vivo prediction of inductive drug interactions, we determined induction of
      various P450s and drug transporters by the anti-human deficiency virus protease
      inhibitors (PIs) and the prototypic inducer, rifampin, in LS180 cells. Among
      these proteins, the various PIs significantly induced (n = 3-5) only CYP3A4 and
      multidrug resistance transporter 1 (MDR1) transcripts (2- to 50-fold). CYP3A4
      activity (1'-hydroxymidazolam formation) was increased (2-fold) by rifampin (10
      microM) but was reduced by the PIs (1.5- to 7-fold). Surprisingly, constitutive
      androstane receptor 1 (CAR1) was not found to be expressed in these cells.
      Additionally, using a reporter assay, we found that PIs did not activate CAR3
      (the natural splice variant of CAR1) but significantly activated PXR (2- to 24
      fold), which correlated well with induction of CYP3A4 and MDR1 transcripts
      (approximately r = 0.9). Furthermore, in a PXR-knockdown stable LS180 cell line,
      induction of CYP3A4 and MDR1 mRNA after treatment with PIs and rifampin was
      significantly reduced (1.4- to 5-fold) compared with that in PXR nonsilenced
      cells. Based on these data, we conclude that LS180 cells could be used as a
      readily available, high-throughput cell line to screen for PXR-mediated induction
      of CYP3A4 and MDR1 transcripts. These data also indicate that the majority of the
      PIs are likely to produce intestinal drug-drug interactions by inactivating or
      inhibiting CYP3A enzymes even though they induce CYP3A4 and MDR1 transcripts via
      PXR.

PMID- 18332087
TI  - Native human zona pellucida glycoproteins: purification and binding properties.
AB  - BACKGROUND: Fertilization starts with the binding of the spermatozoa to the zona
      pellucida (ZP) of the oocyte. Such binding is a carbohydrate-mediated event and
      consists of a series of tightly regulated events. Molecular interactions between
      spermatozoon and ZP in human are not well characterized due to limited
      availability of oocytes for research. Our current technology cannot generate
      recombinant human ZP (hZP) glycoproteins with native glycosylation. METHODS AND
      RESULTS: In this study, hZP glycoproteins, hZP2 (approximately 120 kDa), hZP3
      (approximately 58 kDa) and hZP4 (approximately 65 kDa) were purified from ZP
      (purity >88%) by immunoaffinity columns. The binding sites of the purified native
      hZP3 and hZP4 were localized to the acrosome region of the capacitated human
      spermatozoa, and were lost after acrosome reaction. Purified human hZP2 bound to
      this region only in acrosome-reacted spermatozoa. Differential binding of the
      three glycoproteins to the post-acrosomal region and the midpiece of the
      spermatozoa was observed. In addition, hZP3, but not hZP2 and hZP4, induced
      hyperactivation. The stimulatory activity was dependent partly on N-linked
      glycosylation of hZP3. CONCLUSIONS: This manuscript describes the biological
      activities of purified hZP glycoproteins from the native source for the first
      time.

PMID- 18332088
TI  - L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis.
AB  - BACKGROUND: Endometriosis is a benign and progressive disease with a high
      prevalence. Women with endometriosis, especially with atypical endometriosis,
      have a higher probability for developing ovarian cancer compared with women
      without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in
      ovarian and endometrial carcinomas and is associated with a bad prognosis. Here,
      we have analysed L1CAM expression in endometriosis. METHODS AND RESULTS: In our
      study with the samples from 79 patients with, and 37 patients without,
      endometriosis, we found that endometriosis cell lines and short-term cultures of
      endometrium from women with endometriosis expressed L1CAM at the mRNA and protein
      level. Quantitative RT-PCR analysis showed that L1CAM was expressed at
      significantly higher level in the epithelial compartment from patients with
      endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical
      staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM
      positive staining. Of these 15 L1CAM-positive samples, 13 were atypical
      endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial
      endometrium cultures from women with endometriosis was able to stimulate neurite
      outgrowth as measured in a chicken ganglion assay. CONCLUSIONS: We propose that
      L1CAM could promote endometriosis development by increasing enervation and
      aggravation. L1CAM expression is higher in atypical endometriosis compared with
      normal endometriosis.

PMID- 18332089
TI  - Small glutamine-rich tetratricopeptide repeat-containing protein alpha (SGTA), a
      candidate gene for polycystic ovary syndrome.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogenic, complex common
      genetic disease. Multiple pathways are involved in its pathogenesis, including
      the androgen signaling pathway and insulin signaling pathway. Small glutamine
      rich tetratricopeptide repeat-containing protein alpha (SGTA) is a putative
      member of the androgen receptor-chaperone-co-chaperone complex, and may play a
      role in androgen signaling as a co-chaperone. Polymorphisms in the SGTA gene have
      not been evaluated for a role in PCOS. METHODS: Women with and without PCOS (287
      cases, 187 controls) were genotyped for three single nucleotide polymorphisms
      (SNPs) in SGTA. SNPs and haplotypes were determined and tested for association
      with PCOS and component traits of PCOS. RESULTS: For SNP rs1640262, homozygotes
      for the minor allele were protected against PCOS (P = 0.009). Haplotype 1 (G-A-T)
      was associated with increased risk of PCOS (P = 0.015). In women with PCOS,
      haplotype 2 (A-G-C) was associated with increased insulin resistance (P = 0.013),
      consequently resulting in increased insulin secretion (P = 0.014). CONCLUSIONS:
      This study presents genetic evidence suggesting a potential role of SGTA in the
      pathogenesis of PCOS. SGTA may provide a connection between multiple pathways in
      PCOS.

PMID- 18332090
TI  - Interleukin-1 receptor antagonist gene (IL-1RN) polymorphism is a predictive
      factor of clinical pregnancy after IVF.
AB  - BACKGROUND: Only 25% of IVF transfer cycles lead to a clinical pregnancy, calling
      for continued technical progress but also more in depth analysis of patients'
      individual characteristics. The interleukin-1 (IL-1) system and matrix
      metalloproteinases (MMPs) are strongly implicated in embryo implantation. The
      genes coding for IL-1Ra (gene symbol IL-1RN), IL-1beta, MMP2 and MMP9 bear
      functional polymorphisms. We analysed the maternal genetic profile at these
      polymorphic sites in IVF patients, to determine possible correlations with IVF
      outcome. METHODS: One hundred and sixty women undergoing an IVF cycle were
      enrolled and a buccal smear was obtained. The presence of IL-1RN variable number
      of tandem repeats and IL-1B + 3953, MMP2-1306 and MMP9-1562 single nucleotide
      substitutions were determined. Patients were divided into pregnancy failures
      (119), biochemical pregnancies (8) and clinical pregnancies (33). RESULTS: There
      was a 40% decrease in IL-1RN*2 allele frequency (P = 0.024) and a 45% decrease in
      IL-1RN*2 carrier status in the clinical pregnancy group as compared to the
      pregnancy failure group (P = 0.017). This decrease was still statistically
      significant after a multivariate logistic regression analysis. The likelihood of
      a clinical pregnancy was decreased accordingly in IL-1RN*2 carriers: odds ratio =
      0.349, 95% confidence interval = 0.2-0.8, P = 0.017. The IL-1B, MMP2 and MMP9
      polymorphisms showed no correlation with IVF outcome. CONCLUSIONS: IL-1RN*2
      allele carriage is associated with a poor prognosis of achieving a pregnancy
      after IVF.

PMID- 18332091
TI  - Distinct classes of trafficking rBAT mutants cause the type I cystinuria
      phenotype.
AB  - Most mutations in the rBAT subunit of the heterodimeric cystine transporter rBAT
      b(0,+)AT cause type I cystinuria. Trafficking of the transporter requires the
      intracellular assembly of the two subunits. Without its partner, rBAT, but not
      b(0,+)AT, is rapidly degraded. We analyzed the initial biogenesis of wild-type
      rBAT and type I cystinuria rBAT mutants. rBAT was degraded, at least in part, via
      the ERAD pathway. Assembly with b(0,+)AT within the endoplasmic reticulum (ER)
      blocked rBAT degradation and could be independent of the calnexin chaperone
      system. This system was, however, necessary for post-assembly maturation of the
      heterodimer. Without b(0,+)AT, wild-type and rBAT mutants were degraded with
      similar kinetics. In its presence, rBAT mutants showed strongly reduced (L89P) or
      no transport activity, failed to acquire complex N-glycosylation and to
      oligomerize, suggesting assembly and/or folding defects. Most of the
      transmembrane domain mutant L89P did not heterodimerize with b(0,+)AT and was
      degraded. However, the few [L89P]rBAT-b(0,+)AT heterodimers were stable,
      consistent with assembly, but not folding, defects. Mutants of the rBAT
      extracellular domain (T216M, R365W, M467K and M467T) efficiently assembled with
      b(0,+)AT but were subsequently degraded. Together with earlier results, the data
      suggest a two-step biogenesis model, with the early assembly of the subunits
      followed by folding of the rBAT extracellular domain. Defects on either of these
      steps lead to the type I cystinuria phenotype.

PMID- 18332092
TI  - De novo bacterial genome sequencing: millions of very short reads assembled on a
      desktop computer.
AB  - Novel high-throughput DNA sequencing technologies allow researchers to
      characterize a bacterial genome during a single experiment and at a moderate
      cost. However, the increase in sequencing throughput that is allowed by using
      such platforms is obtained at the expense of individual sequence read length,
      which must be assembled into longer contigs to be exploitable. This study focuses
      on the Illumina sequencing platform that produces millions of very short
      sequences that are 35 bases in length. We propose a de novo assembler software
      that is dedicated to process such data. Based on a classical overlap graph
      representation and on the detection of potentially spurious reads, our software
      generates a set of accurate contigs of several kilobases that cover most of the
      bacterial genome. The assembly results were validated by comparing data sets that
      were obtained experimentally for Staphylococcus aureus strain MW2 and
      Helicobacter acinonychis strain Sheeba with that of their published genomes
      acquired by conventional sequencing of 1.5- to 3.0-kb fragments. We also provide
      indications that the broad coverage achieved by high-throughput sequencing might
      allow for the detection of clonal polymorphisms in the set of DNA molecules being
      sequenced.

PMID- 18332093
TI  - Haptoglobin genotype: a determinant of cardiovascular complication risk in type 1
      diabetes.
AB  - OBJECTIVE: Haptoglobin is a plasma protein that binds free hemoglobin, thereby
      inhibiting hemoglobin-induced oxidative damage. We investigated the association
      between the haptoglobin genotype and the incidence of coronary artery disease
      (CAD) in a cohort of individuals with childhood-onset type 1 diabetes. RESEARCH
      DESIGN AND METHODS: Participants from the Epidemiology of Diabetes Complications
      Study who were free of CAD at study entry and had DNA available were selected (n
      = 453, mean age 27.1 years, and diabetes duration 18.8 years). CAD was defined as
      angina, ischemic electrocardiogram, myocardial infarction confirmed by Q-waves on
      electrocardiogram or hospital records, angiographic stenosis >50%, or
      revascularization. RESULTS: The proportions of the cohort with the haptoglobin
      1/1, 2/1, and 2/2 genotypes were 11.5, 41.3, and 47.2%, respectively. During 18
      years of follow-up, there were 135 (29.8%) incident CAD events. Univariately, the
      proportion of CAD events increased from 15.4 to 28.3 and 34.6% for haptoglobin
      1/1, 2/1, and 2/2, respectively (P = 0.02, P-trend = 0.007). Cumulative incidence
      (including 33 baseline prevalent cases) also increased from 24.1 to 32.3 and
      39.1%, respectively (P = 0.07, P-trend = 0.02). In Cox proportional hazards
      models adjusting for traditional CAD risk factors, the haptoglobin 2/2 genotype
      was associated with increased CAD incidence compared with the haptoglobin 1/1
      genotype (hazard ratio [HR] 2.21, 95% CI 1.05-4.65, P = 0.04). Although the risk
      associated with the haptoglobin 2/1 genotype did not reach significance (1.78,
      0.84-3.79, P = 0.13), there remained a significant trend across the three groups
      (P = 0.03). CONCLUSIONS: These data support the hypothesis that the haptoglobin
      genotype influences cardiovascular risk in type 1 diabetes.

PMID- 18332094
TI  - Distal degenerative sensory neuropathy in a long-term type 2 diabetes rat model.
AB  - OBJECTIVE: Peripheral neuropathy associated with type 2 diabetes (DPN) is not
      widely modeled. We describe unique features of DPN in type 2 diabetic Zucker
      diabetic fatty (ZDF) rats. RESEARCH DESIGN AND METHODS: We evaluated the
      structural, electrophysiological, behavioral, and molecular features of DPN in
      ZDF rats and littermates over 4 months of hyperglycemia. The status of insulin
      signaling transduction molecules that might be interrupted in type 2 diabetes and
      selected survival-, stress-, and pain-related molecules was emphasized in dorsal
      root ganglia (DRG) sensory neurons. RESULTS: ZDF rats developed slowing of motor
      sciatic-tibial and sensory sciatic digital conduction velocity and selective
      mechanical allodynia with preserved thermal algesia. Diabetic sural axons,
      preserved in number, developed atrophy, but there was loss of large-calibre
      dermal and small-calibre epidermal axons. In diabetic rats, insulin signal
      transduction pathways in lumbar DRGs were preserved or had trends toward
      upregulation: mRNA levels of insulin receptor beta-subunit (IRbeta), insulin
      receptor substrate (IRS)-1, and IRS-2. The numbers of neurons expressing IRbeta
      protein were also preserved. There were trends toward early rises of mRNA levels
      of heat shock protein 27 (HSP27), the alpha2delta1 calcium channel subunit, and
      phosphatidylinositol 3-kinase in diabetes. Others were unchanged, including
      nuclear factor-kappaB (NF-kappaB; p50/p105) and receptor for advanced
      glycosylation endproducts (RAGE) as was the proportion of neurons expressing
      HSP27, NF-kappaB, and RAGE protein. CONCLUSIONS: ZDF type 2 diabetic rats develop
      a distal degenerative sensory neuropathy accompanied by a selective long-term
      pain syndrome. Neuronal insulin signal transduction molecules are preserved.

PMID- 18332095
TI  - Central nervous system neuropeptide Y signaling modulates VLDL triglyceride
      secretion.
AB  - OBJECTIVE: Elevated triglyceride (TG) is the major plasma lipid abnormality in
      obese and diabetic patients and contributes to cardiovascular morbidity in these
      disorders. We sought to identify novel mechanisms leading to
      hypertriglyceridemia. Resistance to negative feedback signals from adipose tissue
      in key central nervous system (CNS) energy homeostatic circuits contributes to
      the development of obesity. Because triglycerides both represent the largest
      energy depot in the body and are elevated in both the plasma and adipose in
      obesity and diabetes, we hypothesized that the same neural circuits that regulate
      energy balance also regulate the secretion of TGs into plasma. RESEARCH DESIGN
      AND METHODS: In normal fasting rats, the TG secretion rate was estimated by
      serial blood sampling after intravascular tyloxapol pretreatment. Neuropeptide Y
      (NPY) signaling in the CNS was modulated by intracerebroventricular injection of
      NPY, receptor antagonist, and receptor agonist. RESULTS: A single
      intracerebroventricular injection of NPY increased TG secretion by 2.5-fold in
      the absence of food intake, and this was determined to be VLDL by fast
      performance liquid chromatography (FPLC). This effect was recapitulated by
      activating NPY signaling in downstream neurons with an NPY-Y5 receptor agonist.
      An NPY-Y1 receptor antagonist decreased the elevated TGs in the form of VLDL
      secretion rate by 50% compared with vehicle. Increased TG secretion was due to
      increased secretion of VLDL particles, rather than secretion of larger particles,
      because apolipoprotein B100 was elevated in FPLC fractions corresponding to VLDL.
      CONCLUSIONS: We find that a key neuropeptide system involved in energy
      homeostasis in the CNS exerts control over VLDL-TG secretion into the
      bloodstream.

PMID- 18332096
TI  - Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to
      obesity.
AB  - OBJECTIVE: Kinins mediate pathophysiological processes related to hypertension,
      pain, and inflammation through the activation of two G-protein-coupled receptors,
      named B(1) and B(2). Although these peptides have been related to glucose
      homeostasis, their effects on energy balance are still unknown. RESEARCH DESIGN
      AND METHODS: Using genetic and pharmacological strategies to abrogate the kinin
      B(1) receptor in different animal models of obesity, here we present evidence of
      a novel role for kinins in the regulation of satiety and adiposity. RESULTS:
      Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content,
      hypoleptinemia, increased leptin sensitivity, and robust protection against high
      fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited
      reduced food intake, improved lipid oxidation, and increased energy expenditure.
      Surprisingly, B(1) receptor deficiency was not able to decrease food intake and
      adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/
      ) mice were more responsive to the effects of exogenous leptin on body weight and
      food intake, suggesting that B(1) receptors may be dependent on leptin to display
      their metabolic roles. Finally, inhibition of weight gain and food intake by B(1)
      receptor ablation was pharmacologically confirmed by long-term administration of
      the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet.
      CONCLUSIONS: Our data suggest that kinin B(1) receptors participate in the
      regulation of the energy balance via a mechanism that could involve the
      modulation of leptin sensitivity.

PMID- 18332097
TI  - Retinal and cerebral microvascular signs and diabetes: the age, gene/environment
      susceptibility-Reykjavik study.
AB  - OBJECTIVE: Diabetes increases the risk for microvascular disease. The retina and
      the brain both have intricate microvascular systems that are developmentally
      similar. We sought to examine whether microvascular lesions in the retina and in
      the brain are associated and whether this association differs among people with
      and without diabetes. RESEARCH DESIGN AND METHODS: The analysis included 4,218
      participants of the Icelandic population-based Age, Gene/Environment
      Susceptibility-Reykjavik Study who were born in 1907-1935 and who were previously
      followed as a part of the Reykjavik Study. Retinal focal arteriolar narrowing,
      arteriovenous (AV) nicking, and microaneurysms/hemorrhages were evaluated on
      digital retinal images of both eyes. Cerebral microbleeds (CMBs) were evaluated
      from magnetic resonance images. Data were analyzed with logistic and multinomial
      logistic regression models controlling for demographics, major cardiovascular
      risk factors, cerebral infarcts, and white matter lesions. RESULTS: Evidence of
      brain microbleeds was found in 485 (11.5%) people, including 192 with multiple
      (>or=2) microbleeds. Subjects with signs of retinal microvascular lesions were at
      a significantly increased likelihood for having multiple CMBs. People with
      diabetes in combination with the presence of either retinal AV nicking (odds
      ratio [OR] 2.47 [95% CI 1.42-4.31]) or retinal microaneurysms/hemorrhages (2.28
      [1.24-4.18]) were significantly more likely to have multiple CMBs. CONCLUSIONS:
      Retinal microvascular abnormalities and brain microbleeds may occur together in
      older adults. People with both diabetes and signs of retinal microvascular
      lesions (AV nicking and microaneurysms/hemorrhages) are more likely to have
      multiple microbleeds in the brain. Microvascular disease in diabetes extends to
      the brain.

PMID- 18332098
TI  - Sequencing-based genotyping and association analysis of the MICA and MICB genes
      in type 1 diabetes.
AB  - OBJECTIVE: The nonclassical major histocompatibility complex (MHC) class I chain
      related molecules (MICs), encoded within the MHC, function in immunity. The
      transmembrane polymorphism in MICA (MICA-STR) has been reported to be associated
      with type 1 diabetes. In this study, we directly sequenced both of the highly
      polymorphic MIC genes (MICA and MICB) in order to establish whether they are
      associated with type 1 diabetes independently of the known type 1 diabetes MHC
      class II genes HLA-DRB1 and HLA-DQB1. RESEARCH DESIGN AND METHODS: We developed a
      sequencing-based typing method and genotyped MICA and MICB in 818 families (2,944
      individuals) with type 1 diabetes from the U.K. and U.S. (constructing the
      genotype from single nucleotide polymorphisms in exons 2-4 of MICA and 2-5 of
      MICB) and additionally genotyped the MICA-STR in 2,023 type 1 diabetic case
      subjects and 1,748 control subjects from the U.K. We analyzed the association of
      the MICA and MICB alleles and genotypes with type 1 diabetes using regression
      methods. RESULTS: We identified known MICA and MICB alleles and discovered four
      new MICB alleles. Based on this large-scale and detailed genotype data, we found
      no evidence for association of MICA and MICB with type 1 diabetes independently
      of the MHC class II genes (MICA P = 0.08, MICA-STR P = 0.76, MICB P = 0.03, after
      conditioning on HLA-DRB1 and HLA-DQB1). CONCLUSIONS: Common MICA and MICB genetic
      variations including the MICA-STR are not associated, in a primary way, with
      susceptibility to type 1 diabetes.

PMID- 18332099
TI  - Beta-cell dysfunction in subjects with impaired glucose tolerance and early type
      2 diabetes: comparison of surrogate markers with first-phase insulin secretion
      from an intravenous glucose tolerance test.
AB  - OBJECTIVE: Methods to assess beta-cell function in clinical studies are limited.
      The aim of the current study was to compare a direct measure of insulin secretion
      with fasting surrogate markers in relation to glucose tolerance status. RESEARCH
      DESIGN AND METHODS: In 1,380 individuals from the Insulin Resistance
      Atherosclerosis Study, beta-cell function was assessed using a frequently sampled
      intravenous glucose tolerance test (first-phase insulin secretion; acute insulin
      response [AIR]), homeostasis model assessment of beta-cell function (HOMA-B),
      proinsulin levels, and the proinsulin-to-insulin ratio. Beta-cell function was
      cross-sectionally analyzed by glucose tolerance categories (normal glucose
      tolerance [NGT], n = 712; impaired glucose tolerance [IGT], n = 353; newly
      diagnosed diabetes by 2-h glucose from an oral glucose tolerance test [OGTT]
      [DM2h], n = 80; newly diagnosed diabetes by fasting glucose [DMf], n = 135; or
      newly diagnosed diabetes by fasting and 2-h glucose and established diabetes on
      diet/exercise only [DM], n = 100). RESULTS: In Spearman correlation analyses,
      proinsulin and the proinsulin-to-insulin ratio were only modestly inversely
      related to AIR (r values from -0.02 to -0.27), and AIR was strongly related to
      HOMA-B (r values 0.56 and 0.58). HOMA-B markedly underestimated the magnitude of
      the beta-cell defect across declining glucose tolerance, especially for IGT and
      new DM by OGTT compared with AIR. Analyses adjusting for insulin sensitivity
      showed that beta-cell function was compromised in IGT, DM2h, DMf, and DM,
      relative to NGT, by 13, 12, 59, and 62% (HOMA-B) and by as much as 40, 60, 80,
      and 75%, using AIR. CONCLUSIONS: Subjects with IGT and early-stage, asymptomatic
      type 2 diabetic patients have more pronounced beta-cell defects than previously
      estimated from epidemiological studies using homeostasis model assessment.

PMID- 18332100
TI  - Identification of tyrosine phosphatase 2(256-760) construct as a new, sensitive
      marker for the detection of islet autoimmunity in type 2 diabetic patients: the
      non-insulin requiring autoimmune diabetes (NIRAD) study 2.
AB  - OBJECTIVE: The presence of autoantibodies to islet antigens GAD and/or tyrosine
      phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in
      adults [LADA]) identifies subjects at high risk to develop insulin dependency.
      The aim of this study was to dissect humoral anti-IA-2 immune response in
      Caucasian LADA patients, identifying the most sensitive construct to evaluate IA
      2 immunoreactivity and comparing LADA IA-2 epitope specificities to those found
      in type 1 diabetes. RESEARCH DESIGN AND METHODS: We analyzed 177 LADA and 978
      type 2 diabetic patients with different disease duration, collected in a
      nationwide Italian survey, the Non-Insulin Requiring Autoimmune Diabetes (NIRAD)
      study aimed at assessing prevalence and characteristics of autoimmune diabetes in
      type 2 diabetic patients and 106 newly diagnosed type 1 diabetic patients (53
      children, 53 adults). By radioimmunoassay, we analyzed humoral immunoreactivity
      to seven IA-2 constructs: IA-2(PTP (687-979)), IA-2((761-964)), IA-2((256-760)),
      IA-2(JM (601-630)), IA-2(IC (605-979)), IA-2(BDC (256-556:630-979)), and IA-2(FL
      (1-979)). RESULTS: IA-2((256-760)) fragment was identified as the marker with the
      highest sensitivity for detection of humoral IA-2 immunoreactivity in LADA
      patients, identifying IA-2 autoantibodies in approximately 30% of GAD antibody
      (GADA)-positive LADA patients and in 3.4% of GADA-negative type 2 diabetic
      patients. LADA IA-2((256-760))A positivity was associated with an increased
      frequency of autoimmune diabetes HLA-susceptible genotypes and with a higher risk
      for developing thyroid autoimmunity compared with autoantibody-negative type 2
      diabetic patients. At disease diagnosis, adult-onset type 1 diabetic and LADA
      patients showed a lower IA-2 COOH-terminal immunoreactivity compared with
      childhood-onset type 1 diabetic patients. CONCLUSIONS: IA-2 immunoreactivity in
      LADA patients has thus far been underestimated, and IA-2((256-760)) autoantibody
      detection may represent a novel diagnostic tool for the identification of islet
      autoimmunity in these patients.

PMID- 18332101
TI  - Common variants in maturity-onset diabetes of the young genes and future risk of
      type 2 diabetes.
AB  - OBJECTIVE: Mutations in the hepatocyte nuclear factor (HNF)-1alpha, HNF-4alpha,
      glucokinase (GCK), and HNF-1beta genes cause maturity-onset diabetes of the young
      (MODY), but it is not known whether common variants in these genes predict future
      type 2 diabetes. RESEARCH DESIGN AND METHODS: We tested 14 previously associated
      polymorphisms in HNF-1alpha, HNF-4alpha, GCK, and HNF-1beta for association with
      type 2 diabetes-related traits and future risk of type 2 diabetes in 2,293
      individuals from the Botnia study (Finland) and in 15,538 individuals from the
      Malmo Preventive Project (Sweden) with a total follow-up >360,000 years. RESULTS:
      The polymorphism rs1169288 in HNF-1alpha strongly predicted future type 2
      diabetes (hazard ratio [HR] 1.2, P = 0.0002). Also, SNPs rs4810424 and rs3212198
      in HNF-4alpha nominally predicted future type 2 diabetes (HR 1.3 [95% CI 1.0
      1.6], P = 0.03; and 1.1 [1.0-1.2], P = 0.04). The rs2144908 polymorphism in HNF
      4alpha was associated with elevated rate of hepatic glucose production during a
      hyperinsulinemic-euglycemic clamp (P = 0.03) but not with deterioration of
      insulin secretion over time. The SNP rs1799884 in the GCK promoter was associated
      with elevated fasting plasma glucose (fPG) concentrations that remained unchanged
      during the follow-up period (P = 0.4; SE 0.004 [-0.003-0.007]) but did not
      predict future type 2 diabetes (HR 0.9 [0.8-1.0], P = 0.1). Polymorphisms in HNF
      1beta (transcription factor 2 [TCF2]) did not significantly influence insulin or
      glucose values nor did they predict future type 2 diabetes. CONCLUSIONS: In
      conclusion, genetic variation in both HNF-1alpha and HNF-4alpha predict future
      type 2 diabetes, whereas variation in the GCK promoter results in a sustained but
      subtle elevation of fPG that is not sufficient to increase risk for future type 2
      diabetes.

PMID- 18332102
TI  - Nischarin inhibits LIM kinase to regulate cofilin phosphorylation and cell
      invasion.
AB  - Nischarin is a novel protein that regulates cell migration by inhibiting p21
      activated kinase (PAK). LIM kinase (LIMK) is a downstream effector of PAK, and it
      is known to play an important role in cell invasion. Here we show that nischarin
      also associates with LIMK to inhibit LIMK activation, cofilin phosphorylation,
      and LIMK-mediated invasion of breast cancer cells, suggesting that nischarin
      regulates cell invasion by negative modulation of the LIMK/cofilin pathway. The
      amino terminus of nischarin binds to the PDZ and kinase domains of LIMK. Although
      LIMK activation enhances the interaction with nischarin, only phosphorylation of
      threonine 508 of LIMK is crucial for the interaction. Inhibition of endogenous
      nischarin expression by RNA interference stimulates breast cancer cell invasion.
      Also, nischarin small interfering RNA (siRNA) enhances cofilin phosphorylation.
      In addition, knock-down of nischarin showed branched projection actin structures.
      Collectively these data indicate that nischarin siRNA may enhance random
      migration, resulting in stimulation of invasion.

PMID- 18332103
TI  - Fibroblast growth factor receptor 2 phosphorylation on serine 779 couples to 14-3
      3 and regulates cell survival and proliferation.
AB  - The fibroblast growth factors (FGFs) exert their diverse (or pleiotropic)
      biological responses through the binding and activation of specific cell surface
      receptors (FGFRs). While FGFRs are known to initiate intracellular signaling
      through receptor tyrosine phosphorylation, the precise mechanisms by which the
      FGFRs regulate pleiotropic biological responses remain unclear. We now identify a
      new mechanism by which FGFR2 is able to regulate intracellular signaling and
      cellular responses. We show that FGFR2 is phosphorylated on serine 779 (S779) in
      response to FGF2. S779, which lies adjacent to the phospholipase Cgamma binding
      site at Y766, provides a docking site for the 14-3-3 phosphoserine-binding
      proteins and is essential for the full activation of the phosphatidylinositol 3
      kinase and Ras/mitogen-activated protein kinase pathways. Furthermore, S779
      signaling is essential for promoting cell survival and proliferation in both
      Ba/F3 cells and BALB/c 3T3 fibroblasts. This new mode of FGFR2 phosphoserine
      signaling via the 14-3-3 proteins may provide an increased repertoire of
      signaling outputs to allow the regulation of pleiotropic biological responses. In
      this regard, we have identified conserved putative phosphotyrosine/phosphoserine
      motifs in the cytoplasmic domains of diverse cell surface receptors, suggesting
      that they may perform important functional roles beyond the FGFRs.

PMID- 18332104
TI  - DEK is a poly(ADP-ribose) acceptor in apoptosis and mediates resistance to
      genotoxic stress.
AB  - DEK is a nuclear phosphoprotein implicated in oncogenesis and autoimmunity and a
      major component of metazoan chromatin. The intracellular cues that control the
      binding of DEK to DNA and its pleiotropic functions in DNA- and RNA-dependent
      processes have remained mainly elusive so far. Our recent finding that the
      phosphorylation status of DEK is altered during death receptor-mediated apoptosis
      suggested a potential involvement of DEK in stress signaling. In this study, we
      show that in cells committed to die, a portion of the cellular DEK pool is
      extensively posttranslationally modified by phosphorylation and poly(ADP
      ribosyl)ation. Through interference with DEK expression, we further show that DEK
      promotes the repair of DNA lesions and protects cells from genotoxic agents that
      typically trigger poly(ADP-ribose) polymerase activation. The posttranslational
      modification of DEK during apoptosis is accompanied by the removal of the protein
      from chromatin and its release into the extracellular space. Released modified
      DEK is recognized by autoantibodies present in the synovial fluids of patients
      affected by juvenile rheumatoid arthritis/juvenile idiopathic arthritis. These
      findings point to a crucial role of poly(ADP-ribosyl)ation in shaping DEK's
      autoantigenic properties and in its function as a promoter of cell survival.

PMID- 18332105
TI  - MURC, a muscle-restricted coiled-coil protein that modulates the Rho/ROCK
      pathway, induces cardiac dysfunction and conduction disturbance.
AB  - We identified a novel muscle-restricted putative coiled-coil protein, MURC, which
      is evolutionarily conserved from frog to human. MURC was localized to the
      cytoplasm with accumulation in the Z-line of the sarcomere in the murine adult
      heart. MURC mRNA expression in the heart increased during the developmental
      process from the embryonic stage to adulthood. In response to pressure overload,
      MURC mRNA expression increased in the hypertrophied heart. Using the yeast two
      hybrid system, we identified the serum deprivation response (SDPR) protein, a
      phosphatidylserine-binding protein, as a MURC-binding protein. MURC induced
      activation of the RhoA/ROCK pathway, which modulated serum response factor
      mediated atrial natriuretic peptide (ANP) expression and myofibrillar
      organization. SDPR augmented MURC-induced transactivation of the ANP promoter in
      cardiomyocytes, and RNA interference of SDPR attenuated the action of MURC on the
      ANP promoter. Transgenic mice expressing cardiac-specific MURC (Tg-MURC)
      exhibited cardiac contractile dysfunction and atrioventricular (AV) conduction
      disturbances with atrial chamber enlargement, reduced thickness of the
      ventricular wall, and interstitial fibrosis. Spontaneous episodes of atrial
      fibrillation and AV block were observed in Tg-MURC mice. These findings indicate
      that MURC modulates RhoA signaling and that MURC plays an important role in the
      development of cardiac dysfunction and conduction disturbance with increased
      vulnerability to atrial arrhythmias.

PMID- 18332106
TI  - Histone deacetylase 5 acquires calcium/calmodulin-dependent kinase II
      responsiveness by oligomerization with histone deacetylase 4.
AB  - Calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates histone
      deacetylase 4 (HDAC4), a class IIa HDAC, resulting in the cytosolic accumulation
      of HDAC4 and the derepression of the transcription factor myocyte enhancer factor
      2. Phosphorylation by CaMKII requires docking of the kinase to a specific domain
      of HDAC4 not present in other HDACs. Paradoxically, however, CaMKII signaling can
      also promote the nuclear export of other class IIa HDACs, such as HDAC5. Here, we
      show that HDAC4 and HDAC5 form homo- and hetero-oligomers via a conserved coiled
      coil domain near their amino termini. Whereas HDAC5 alone is unresponsive to
      CaMKII, it becomes responsive to CaMKII in the presence of HDAC4. The acquisition
      of CaMKII responsiveness by HDAC5 is mediated by HDAC5's direct association with
      HDAC4 and can occur by phosphorylation of HDAC4 or by transphosphorylation by
      CaMKII bound to HDAC4. Thus, HDAC4 integrates upstream Ca(2+)-dependent signals
      via its association with CaMKII and transmits these signals to HDAC5 by protein
      protein interactions. We conclude that HDAC4 represents a point of convergence
      for CaMKII signaling to downstream HDAC-regulated genes, and we suggest that
      modulation of the interaction of CaMKII and HDAC4 represents a means of
      regulating CaMKII-dependent gene programs.

PMID- 18332107
TI  - Histone deacetylase inhibitor depsipeptide activates silenced genes through
      decreasing both CpG and H3K9 methylation on the promoter.
AB  - Histone deacetylase inhibitor (HDACi) has been shown to demethylate the mammalian
      genome, which further strengthens the concept that DNA methylation and histone
      modifications interact in regulation of gene expression. Here, we report that an
      HDAC inhibitor, depsipeptide, exhibited significant demethylating activity on the
      promoters of several genes, including p16, SALL3, and GATA4 in human lung cancer
      cell lines H719 and H23, colon cancer cell line HT-29, and pancreatic cancer cell
      line PANC1. Although expression of DNA methyltransferase 1 (DNMT1) was not
      affected by depsipeptide, a decrease in binding of DNMT1 to the promoter of these
      genes played a dominant role in depsipeptide-induced demethylation and
      reactivation. Depsipeptide also suppressed expression of histone
      methyltransferases G9A and SUV39H1, which in turn resulted in a decrease of di-
      and trimethylated H3K9 around these genes' promoter. Furthermore, both loading of
      heterochromatin-associated protein 1 (HP1alpha and HP1beta) to methylated H3K9
      and binding of DNMT1 to these genes' promoter were significantly reduced in
      depsipeptide-treated cells. Similar DNA demethylation was induced by another HDAC
      inhibitor, apicidin, but not by trichostatin A. Our data describe a novel
      mechanism of HDACi-mediated DNA demethylation via suppression of histone
      methyltransferases and reduced recruitment of HP1 and DNMT1 to the genes'
      promoter.

PMID- 18332108
TI  - Transcription regulation of the rRNA gene by a multifunctional nucleolar protein,
      B23/nucleophosmin, through its histone chaperone activity.
AB  - It is well established that the transcription rate of the rRNA gene is closely
      associated with profound alterations in the cell growth rate. Regulation of rRNA
      gene transcription is likely to be dependent on the dynamic conversion of the
      chromatin structure. Previously, we identified B23/nucleophosmin, a
      multifunctional nucleolar phosphoprotein, as a component of template activating
      factor III that remodels the chromatin-like structure of the adenovirus genome
      complexed with viral basic proteins. It has also been shown that B23 has histone
      chaperone activity. Here, we examined the effect of B23 on rRNA gene
      transcription. B23 was found to be associated with the rRNA gene chromatin. Small
      interfering-RNA-mediated down-regulation of the B23 expression level resulted in
      reduction of the transcription rate of the rRNA gene. We constructed a B23 mutant
      termed B23DeltaC, which lacks the domain essential for the histone chaperone
      activity and inhibited the histone binding activity of B23 in a dominant-negative
      manner. Expression of B23DeltaC decreased rRNA gene transcription and the rate of
      cell proliferation. These results suggest that B23 is involved in the
      transcription regulation of the rRNA gene as a nucleolar histone chaperone.

PMID- 18332109
TI  - ETO, but not leukemogenic fusion protein AML1/ETO, augments RBP-Jkappa/SHARP
      mediated repression of notch target genes.
AB  - Notch is a transmembrane receptor that determines cell fates and pattern
      formation in all animal species. After specific ligand binding, the intracellular
      part of Notch is cleaved off and translocates to the nucleus, where it targets
      the DNA binding protein RBP-Jkappa. In the absence of Notch, RBP-Jkappa represses
      Notch target genes by recruiting a corepressor complex. We and others have
      previously identified SHARP as one component of this complex. Here, we show that
      the corepressor ETO as well as the leukemogenic fusion protein AML1/ETO directly
      interacts with SHARP, that ETO is part of the endogenous RBP-Jkappa-containing
      corepressor complex, and that ETO is found at Notch target gene promoters. In
      functional assays, corepressor ETO, but not AML1/ETO, augments SHARP-mediated
      repression in an histone deacetylase-dependent manner. Furthermore, either the
      knockdown of ETO or the overexpression of AML1/ETO activates Notch target genes.
      Therefore, we propose that AML1/ETO can disturb the normal, repressive function
      of ETO at Notch target genes. This activating (or derepressing) effect of
      AML1/ETO may contribute to its oncogenic potential in myeloid leukemia.

PMID- 18332110
TI  - Cdc1p is an endoplasmic reticulum-localized putative lipid phosphatase that
      affects Golgi inheritance and actin polarization by activating Ca2+ signaling.
AB  - In the budding yeast Saccharomyces cerevisiae, mutations in the essential gene
      CDC1 cause defects in Golgi inheritance and actin polarization. However, the
      biochemical function of Cdc1p is unknown. Previous work showed that cdc1 mutants
      accumulate intracellular Ca(2+) and display enhanced sensitivity to the
      extracellular Mn(2+) concentration, suggesting that Cdc1p might regulate divalent
      cation homeostasis. By contrast, our data indicate that Cdc1p is a Mn(2+)
      dependent protein that can affect Ca(2+) levels. We identified a cdc1 allele that
      activates Ca(2+) signaling but does not show enhanced sensitivity to the Mn(2+)
      concentration. Furthermore, our studies show that Cdc1p is an endoplasmic
      reticulum-localized transmembrane protein with a putative phosphoesterase domain
      facing the lumen. cdc1 mutant cells accumulate an unidentified phospholipid,
      suggesting that Cdc1p may be a lipid phosphatase. Previous work showed that
      deletion of the plasma membrane Ca(2+) channel Cch1p partially suppressed the
      cdc1 growth phenotype, and we find that deletion of Cch1p also suppresses the
      Golgi inheritance and actin polarization phenotypes. The combined data fit a
      model in which the cdc1 mutant phenotypes result from accumulation of a
      phosphorylated lipid that activates Ca(2+) signaling.

PMID- 18332111
TI  - Involvement of actinin-4 in the recruitment of JRAB/MICAL-L2 to cell-cell
      junctions and the formation of functional tight junctions.
AB  - Tight junctions (TJs) are cell-cell adhesive structures that undergo continuous
      remodeling. We previously demonstrated that Rab13 and a junctional Rab13-binding
      protein (JRAB)/molecule interacting with CasL-like 2 (MICAL-L2) localized at TJs
      and mediated the endocytic recycling of the integral TJ protein occludin and the
      formation of functional TJs. Here, we investigated how JRAB/MICAL-L2 was targeted
      to TJs. Using a series of deletion mutants, we found the plasma membrane (PM)
      targeting domain within JRAB/MICAL-L2. We then identified actinin-4, which was
      originally isolated as an actin-binding protein associated with cell motility and
      cancer invasion/metastasis, as a binding protein for the PM-targeting domain of
      JRAB/MICAL-L2, using a yeast two-hybrid system. Actinin-4 was colocalized with
      JRAB/MICAL-L2 at cell-cell junctions and linked JRAB/MICAL-L2 to F-actin.
      Although actinin-4 bound to JRAB/MICAL-L2 without Rab13, the actinin-4-JRAB/MICAL
      L2 interaction was enhanced by Rab13 activation. Depletion of actinin-4 by using
      small interfering RNA inhibited the recruitment of occludin to TJs during the
      Ca(2+) switch. During the epithelial polarization after replating, JRAB/MICAL-L2
      was recruited from the cytosol to cell-cell junctions. This JRAB/MICAL-L2
      recruitment as well as the formation of functional TJs was delayed in actinin-4
      depleted cells. These results indicate that actinin-4 is involved in recruiting
      JRAB/MICAL-L2 to cell-cell junctions and forming functional TJs.

PMID- 18332112
TI  - Rhythmic SAF-A binding underlies circadian transcription of the Bmal1 gene.
AB  - Although Bmal1 is a key component of the mammalian clock system, little is
      understood about the actual mechanism of circadian Bmal1 gene transcription,
      particularly at the chromatin level. Here we discovered a unique chromatin
      structure within the Bmal1 promoter. The RORE region, which is a critical cis
      element for the circadian regulation of the Bmal1 gene, is comprised of GC-rich
      open chromatin. The 3'-flanking region of the promoter inhibited rhythmic
      transcription in the reporter gene assay in vitro even in the presence of
      RORalpha and REV-ERBalpha. We also found that the nuclear matrix protein SAF-A
      binds to the 3'-flanking region with circadian timing, which was correlated with
      Bmal1 expression by footprinting in vivo. These results suggest that the unique
      chromatin structure containing SAF-A is required for the circadian
      transcriptional regulation of the Bmal1 gene in cells.

PMID- 18332113
TI  - NELF and GAGA factor are linked to promoter-proximal pausing at many genes in
      Drosophila.
AB  - Recent analyses of RNA polymerase II (Pol II) revealed that Pol II is
      concentrated at the promoters of many active and inactive genes. NELF causes Pol
      II to pause in the promoter-proximal region of the hsp70 gene in Drosophila
      melanogaster. In this study, genome-wide location analysis (chromatin
      immunoprecipitation-microarray chip [ChIP-chip] analysis) revealed that NELF is
      concentrated at the 5' ends of 2,111 genes in Drosophila cells. Permanganate
      genomic footprinting was used to determine if paused Pol II colocalized with
      NELF. Forty-six of 56 genes with NELF were found to have paused Pol II. Pol II
      pauses 30 to 50 nucleotides downstream from transcription start sites. Analysis
      of DNA sequences in the vicinity of paused Pol II identified a conserved DNA
      sequence that probably associates with TFIID but detected no evidence of RNA
      secondary structures or other conserved sequences that might directly control
      elongation. ChIP-chip experiments indicate that GAGA factor associates with 39%
      of the genes that have NELF. Surprisingly, NELF associates with almost one-half
      of the most highly expressed genes, indicating that NELF is not necessarily a
      repressor of gene expression. NELF-associated pausing of Pol II might be an
      obligatory but sometimes transient checkpoint during the transcription cycle.

PMID- 18332114
TI  - Interleukin-1 stimulates glutamate uptake in glial cells by accelerating membrane
      trafficking of Na+/K+-ATPase via actin depolymerization.
AB  - Interleukin-1 (IL-1) is a mediator of brain injury induced by ischemia, trauma,
      and chronic neurodegenerative disease. IL-1 also has a protective role by
      preventing neuronal cell death from glutamate neurotoxicity. However, the
      cellular mechanisms of IL-1 action remain unresolved. In the mammalian retina,
      glutamate/aspartate transporter (GLAST) is a Na(+)-dependent, major glutamate
      transporter localized to Muller glial cells, and loss of GLAST leads to
      glaucomatous retinal degeneration (T. Harada, C. Harada, K. Nakamura, H. A. Quah,
      A. Okumura, K. Namekata, T. Saeki, M. Aihara, H. Yoshida, A. Mitani, and K.
      Tanaka, J. Clin. Investig. 117:1763-1770, 2007). We show here that IL-1 increases
      glutamate uptake in Muller cells by a mechanism that involves increased membrane
      Na(+)/K(+)-ATPase localization, required for counteracting the Na(+)-glutamate
      cotransport. IL-1 activated the p38 mitogen-activated protein kinase
      (MAPK)/capase 11 pathway, which destabilizes the actin cytoskeleton allowing
      Na(+)/K(+)-ATPase membrane redistribution. Furthermore, pretreatment with IL-1
      protected retinal neurons from glutamate neurotoxicity through p38 MAPK
      signaling. Our observations suggested that IL-1 acts as a potential
      neuroprotective agent by modulating the functions of the glia-neuron network.

PMID- 18332115
TI  - Multifactorial interplay controls the splicing profile of Alu-derived exons.
AB  - Exonization of Alu elements creates primate-specific genomic diversity. Here we
      combine bioinformatic and experimental methodologies to reconstruct the molecular
      changes leading to exon selection. Our analyses revealed an intricate network
      involved in Alu exonization. A typical Alu element contains multiple sites with
      the potential to serve as 5' splice sites (5'ss). First, we demonstrated the role
      of 5'ss strength in controlling exonization events. Second, we found that a
      cryptic 5'ss enhances the selection of a more upstream site and demonstrate that
      this is mediated by binding of U1 snRNA to the cryptic splice site, challenging
      the traditional role attributed to U1 snRNA of binding the 5'ss only. Third, we
      used a simple algorithm to identify specific sequences that determine splice site
      selection within specific Alu exons. Finally, by inserting identical exons within
      different sequences, we demonstrated the importance of flanking genomic sequences
      in determining whether an Alu exon will undergo exonization. Overall, our results
      demonstrate the complex interplay between at least four interacting layers that
      affect Alu exonization. These results shed light on the mechanism through which
      Alu elements enrich the primate transcriptome and allow a better understanding of
      the exonization process in general.

PMID- 18332116
TI  - SWI/SNF mediates polycomb eviction and epigenetic reprogramming of the INK4b-ARF
      INK4a locus.
AB  - Stable silencing of the INK4b-ARF-INK4a tumor suppressor locus occurs in a
      variety of human cancers, including malignant rhabdoid tumors (MRTs). MRTs are
      extremely aggressive cancers caused by the loss of the hSNF5 subunit of the
      SWI/SNF chromatin-remodeling complex. We found previously that, in MRT cells,
      hSNF5 is required for p16(INK4a) induction, mitotic checkpoint activation, and
      cellular senescence. Here, we investigated how the balance between Polycomb group
      (PcG) silencing and SWI/SNF activation affects epigenetic control of the INK4b
      ARF-INK4a locus in MRT cells. hSNF5 reexpression in MRT cells caused SWI/SNF
      recruitment and activation of p15(INK4b) and p16(INK4a), but not of p14(ARF).
      Gene activation by hSNF5 is strictly dependent on the SWI/SNF motor subunit BRG1.
      SWI/SNF mediates eviction of the PRC1 and PRC2 PcG silencers and extensive
      chromatin reprogramming. Concomitant with PcG complex removal, the mixed lineage
      leukemia 1 (MLL1) protein is recruited and active histone marks supplant
      repressive ones. Strikingly, loss of PcG complexes is accompanied by DNA
      methyltransferase DNMT3B dissociation and reduced DNA methylation. Thus, various
      chromatin states can be modulated by SWI/SNF action. Collectively, these findings
      emphasize the close interconnectivity and dynamics of diverse chromatin
      modifications in cancer and gene control.

PMID- 18332117
TI  - Activator-to-repressor conversion of T-box transcription factors by the Ripply
      family of Groucho/TLE-associated mediators.
AB  - The T-box family of transcription factors, defined by a conserved DNA binding
      domain called the T-box, regulate various aspects of embryogenesis by activating
      and/or repressing downstream genes. In spite of the biological significance of
      the T-box proteins, how they regulate transcription remains to be elucidated.
      Here we show that the Groucho/TLE-associated protein Ripply converts T-box
      proteins from activators to repressors. In cultured cells, zebrafish Ripply1, an
      essential component in somite segmentation, and its structural relatives, Ripply2
      and -3, suppress the transcriptional activation mediated by the T-box protein
      Tbx24, which is coexpressed with ripply1 during segmentation. Ripply1 associates
      with Tbx24 and converts it to a repressor. Ripply1 also antagonizes the
      transcriptional activation of another T-box protein, No tail (Ntl), the zebrafish
      ortholog of Brachyury. Furthermore, injection of a high dosage of ripply1 mRNA
      into zebrafish eggs causes defective development of the posterior trunk, similar
      to the phenotype observed in homozygous mutants of ntl. A mutant form of Ripply1
      defective in association with Tbx24 also lacks activity in zebrafish embryos.
      These results indicate that the intrinsic transcriptional property of T-box
      proteins is controlled by Ripply family proteins, which act as specific adaptors
      that recruit the global corepressor Groucho/TLE to T-box proteins.

PMID- 18332118
TI  - Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice.
AB  - Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible
      factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis. To
      better understand this function in vivo, we have created PHD3(-/-) mice and
      analyzed the neuronal phenotype. Reduced apoptosis in superior cervical ganglion
      (SCG) neurons cultured from PHD3(-/-) mice is associated with an increase in the
      number of cells in the SCG, as well as in the adrenal medulla and carotid body.
      Genetic analysis by intercrossing PHD3(-/-) mice with HIF-1a(+/-) and HIF-2a(+/-)
      mice demonstrated an interaction with HIF-2alpha but not HIF-1alpha, supporting
      the nonredundant involvement of a PHD3-HIF-2alpha pathway in the regulation of
      sympathoadrenal development. Despite the increased number of cells, the
      sympathoadrenal system appeared hypofunctional in PHD3(-/-) mice, with reduced
      target tissue innervation, adrenal medullary secretory capacity, sympathoadrenal
      responses, and systemic blood pressure. These observations suggest that the role
      of PHD3 in sympathoadrenal development extends beyond simple control of cell
      survival and organ mass, with functional PHD3 being required for proper
      anatomical and physiological integrity of the system. Perturbation of this
      interface between developmental and adaptive signaling by hypoxic, metabolic, or
      other stresses could have important effects on key sympathoadrenal functions,
      such as blood pressure regulation.

PMID- 18332119
TI  - A regulatory role of the Rnq1 nonprion domain for prion propagation and
      polyglutamine aggregates.
AB  - Prions are infectious, self-propagating protein conformations. Rnq1 is required
      for the yeast Saccharomyces cerevisiae prion [PIN(+)], which is necessary for the
      de novo induction of a second prion, [PSI(+)]. Here we isolated a [PSI(+)]
      eliminating mutant, Rnq1Delta100, that deletes the nonprion domain of Rnq1.
      Rnq1Delta100 inhibits not only [PSI(+)] prion propagation but also [URE3] prion
      and huntingtin's polyglutamine aggregate propagation in a [PIN(+)] background but
      not in a [pin(-)] background. Rnq1Delta100, however, does not eliminate [PIN(+)].
      These findings are interpreted as showing a possible involvement of the Rnq1
      prion in the maintenance of heterologous prions and polyQ aggregates. Rnq1 and
      Rnq1Delta100 form a sodium dodecyl sulfate-stable and Sis1 (an Hsp40 chaperone
      protein)-containing coaggregate in [PIN(+)] cells. Importantly, Rnq1Delta100 is
      highly QN-rich and prone to self-aggregate or coaggregate with Rnq1 when
      coexpressed in [pin(-)] cells. However, the [pin(-)] Rnq1-Rnq1Delta100
      coaggregate does not represent a prion-like aggregate. These findings suggest
      that [PIN(+)] Rnq1-Rnq1Delta100 aggregates interact with other transmissible and
      nontransmissible amyloids to destabilize them and that the nonprion domain of
      Rnq1 plays a crucial role in self-regulation of the highly reactive QN-rich prion
      domain of Rnq1.

PMID- 18332120
TI  - Bud23 methylates G1575 of 18S rRNA and is required for efficient nuclear export
      of pre-40S subunits.
AB  - BUD23 was identified from a bioinformatics analysis of Saccharomyces cerevisiae
      genes involved in ribosome biogenesis. Deletion of BUD23 leads to severely
      impaired growth, reduced levels of the small (40S) ribosomal subunit, and a block
      in processing 20S rRNA to 18S rRNA, a late step in 40S maturation. Bud23 belongs
      to the S-adenosylmethionine-dependent Rossmann-fold methyltransferase superfamily
      and is related to small-molecule methyltransferases. Nevertheless, we considered
      that Bud23 methylates rRNA. Methylation of G1575 is the only mapped modification
      for which the methylase has not been assigned. Here, we show that this
      modification is lost in bud23 mutants. The nuclear accumulation of the small
      subunit reporters Rps2-green fluorescent protein (GFP) and Rps3-GFP, as well as
      the rRNA processing intermediate, the 5' internal transcribed spacer 1, indicate
      that bud23 mutants are defective for small-subunit export. Mutations in Bud23
      that inactivated its methyltransferase activity complemented a bud23Delta mutant.
      In addition, mutant ribosomes in which G1575 was changed to adenosine supported
      growth comparable to that of cells with wild-type ribosomes. Thus, Bud23 protein,
      but not its methyltransferase activity, is important for biogenesis and export of
      the 40S subunit in yeast.

PMID- 18332121
TI  - Different mechanisms for pseudouridine formation in yeast 5S and 5.8S rRNAs.
AB  - The selection of sites for pseudouridylation in eukaryotic cytoplasmic rRNA
      occurs by the base pairing of the rRNA with specific guide sequences within the
      RNA components of box H/ACA small nucleolar ribonucleoproteins (snoRNPs). Forty
      four of the 46 pseudouridines (Psis) in the cytoplasmic rRNA of Saccharomyces
      cerevisiae have been assigned to guide snoRNAs. Here, we examine the mechanism of
      Psi formation in 5S and 5.8S rRNA in which the unassigned Psis occur. We show
      that while the formation of the Psi in 5.8S rRNA is associated with snoRNP
      activity, the pseudouridylation of 5S rRNA is not. The position of the Psi in
      5.8S rRNA is guided by snoRNA snR43 by using conserved sequence elements that
      also function to guide pseudouridylation elsewhere in the large-subunit rRNA; an
      internal stem-loop that is not part of typical yeast snoRNAs also is conserved in
      snR43. The multisubstrate synthase Pus7 catalyzes the formation of the Psi in 5S
      rRNA at a site that conforms to the 7-nucleotide consensus sequence present in
      other substrates of Pus7. The different mechanisms involved in 5S and 5.8S rRNA
      pseudouridylation, as well as the multiple specificities of the individual trans
      factors concerned, suggest possible roles in linking ribosome production to other
      processes, such as splicing and tRNA synthesis.

PMID- 18332122
TI  - Eukaryotic wobble uridine modifications promote a functionally redundant decoding
      system.
AB  - The translational decoding properties of tRNAs are modulated by naturally
      occurring modifications of their nucleosides. Uridines located at the wobble
      position (nucleoside 34 [U(34)]) in eukaryotic cytoplasmic tRNAs often harbor a 5
      methoxycarbonylmethyl (mcm(5)) or a 5-carbamoylmethyl (ncm(5)) side chain and
      sometimes an additional 2-thio (s(2)) or 2'-O-methyl group. Although a variety of
      models explaining the role of these modifications have been put forth, their in
      vivo functions have not been defined. In this study, we utilized recently
      characterized modification-deficient Saccharomyces cerevisiae cells to test the
      wobble rules in vivo. We show that mcm(5) and ncm(5) side chains promote decoding
      of G-ending codons and that concurrent mcm(5) and s(2) groups improve reading of
      both A- and G-ending codons. Moreover, the observation that the mcm(5)U(34)- and
      some ncm(5)U(34)-containing tRNAs efficiently read G-ending codons challenges the
      notion that eukaryotes do not use U-G wobbling.

PMID- 18332123
TI  - Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha:
      using the receptor LRP-1/CD91 to promote human skin cell migration against a
      TGFbeta-rich environment during wound healing.
AB  - Jump-starting and subsequently maintaining epidermal and dermal cell migration
      are essential processes for skin wound healing. These events are often disrupted
      in nonhealing wounds, causing patient morbidity and even fatality. Currently
      available treatments are unsatisfactory. To identify novel wound-healing targets,
      we investigated secreted molecules from transforming growth factor alpha
      (TGFalpha)-stimulated human keratinoytes, which contained strong motogenic, but
      not mitogenic, activity. Protein purification allowed us to identify the heat
      shock protein 90alpha (hsp90alpha) as the factor fully responsible for the
      motogenic activity in keratinocyte secretion. TGFalpha causes rapid membrane
      translocation and subsequent secretion of hsp90alpha via the unconventional
      exosome pathway in the cells. Secreted hsp90alpha promotes both epidermal and
      dermal cell migration through the surface receptor LRP-1 (LDL receptor-related
      protein 1)/CD91. The promotility activity resides in the middle domain plus the
      charged sequence of hsp90alpha but is independent of the ATPase activity.
      Neutralizing the extracellular function of hsp90alpha blocks TGFalpha-induced
      keratinicyte migration. Most intriguingly, unlike the effects of canonical growth
      factors, the hsp90alpha signaling overrides the inhibition of TGFbeta, an
      abundant inhibitor of dermal cell migration in skin wounds. This finding provides
      a long-sought answer to the question of how dermal cells migrate into the wound
      environment to build new connective tissues and blood vessels. Thus, secreted
      hsp90alpha is potentially a new agent for wound healing.

PMID- 18332124
TI  - A conserved phenylalanine of motif IV in superfamily 2 helicases is required for
      cooperative, ATP-dependent binding of RNA substrates in DEAD-box proteins.
AB  - We have identified a highly conserved phenylalanine in motif IV of the DEAD-box
      helicases that is important for their enzymatic activities. In vivo analyses of
      essential proteins in yeast showed that mutants of this residue had severe growth
      phenotypes. Most of the mutants also were temperature sensitive, which suggested
      that the mutations altered the conformational stability. Intragenic suppressors
      of the F405L mutation in yeast Ded1 mapped close to regions of the protein
      involved in ATP or RNA binding in DEAD-box crystal structures, which implicated a
      defect at this level. In vitro experiments showed that these mutations affected
      ATP binding and hydrolysis as well as strand displacement activity. However, the
      most pronounced effect was the loss of the ATP-dependent cooperative binding of
      the RNA substrates. Sequence analyses and an examination of the Protein Data Bank
      showed that the motif IV phenylalanine is conserved among superfamily 2
      helicases. The phenylalanine appears to be an anchor that maintains the rigidity
      of the RecA-like domain. For DEAD-box proteins, the phenylalanine also aligns a
      highly conserved arginine of motif VI through van der Waals and cation-pi
      interactions, thereby helping to maintain the network of interactions that exist
      between the different motifs involved in ATP and RNA binding.

PMID- 18332125
TI  - PTEN nuclear localization is regulated by oxidative stress and mediates p53
      dependent tumor suppression.
AB  - The tumor suppressor gene PTEN (phosphatase and tensin homologue deleted on
      chromosome 10) is frequently mutated or deleted in various human cancers. PTEN
      localizes predominantly to the cytoplasm and functions as a lipid phosphatase,
      thereby negatively regulating the phosphatidylinositol 3-kinase-AKT signaling
      pathway. PTEN can also localize to the nucleus, where it binds and regulates p53
      protein level and transcription activity. However, the precise function of
      nuclear PTEN and the factors that control PTEN nuclear localization are still
      largely unknown. In this study, we identified oxidative stress as one of the
      physiological stimuli that regulate the accumulation of nuclear PTEN.
      Specifically, oxidative stress inhibits PTEN nuclear export, a process depending
      on phosphorylation of its amino acid residue Ser-380. Nuclear PTEN, independent
      of its phosphatase activity, leads to p53-mediated G(1) growth arrest, cell
      death, and reduction of reactive oxygen species production. Using xenografts
      propagated from human prostate cancer cell lines, we reveal that nuclear PTEN is
      sufficient to reduce tumor progression in vivo in a p53-dependent manner. The
      data outlined in this study suggest a unique role of nuclear PTEN to arrest and
      protect cells upon oxidative damage and to regulate tumorigenesis. Since tumor
      cells are constantly exposed to oxidative stress, our study elucidates the
      cooperative roles of nuclear PTEN with p53 in tumor suppression.

PMID- 18332126
TI  - Signaling through ShcA is required for transforming growth factor beta- and
      Neu/ErbB-2-induced breast cancer cell motility and invasion.
AB  - Cooperation between the Neu/ErbB-2 and transforming growth factor beta (TGF-beta)
      signaling pathways enhances the invasive and metastatic capabilities of breast
      cancer cells; however, the underlying mechanisms mediating this synergy have yet
      to be fully explained. We demonstrate that TGF-beta induces the migration and
      invasion of mammary tumor explants expressing an activated Neu/ErbB-2 receptor,
      which requires signaling from autophosphorylation sites located in the C
      terminus. A systematic analysis of mammary tumor explants expressing Neu/ErbB-2
      add-back receptors that couple to distinct signaling molecules has mapped the
      synergistic effect of TGF-beta-induced motility and invasion to signals emanating
      from tyrosine residues 1226/1227 and 1253 of Neu/ErbB-2. Given that the ShcA
      adaptor protein is known to interact with Neu/ErbB-2 through these residues, we
      investigated the importance of this signaling molecule in TGF-beta-induced cell
      motility and invasion. The reduction of ShcA expression rendered cells expressing
      activated Neu/ErbB-2, or add-back receptors signaling specifically through
      tyrosines 1226/1227 or 1253, unresponsive to TGF-beta-induced motility and
      invasion. In addition, a dominant-negative form of ShcA, lacking its three known
      tyrosine phosphorylation sites, completely abrogates the TGF-beta-induced
      migration and invasion of breast cancer cells expressing activated Neu/ErbB-2.
      Our results implicate signaling through the ShcA adaptor as a key component in
      the synergistic interaction between these pathways.

PMID- 18332127
TI  - Redundant roles of Tead1 and Tead2 in notochord development and the regulation of
      cell proliferation and survival.
AB  - Four members of the TEAD/TEF family of transcription factors are expressed widely
      in mouse embryos and adult tissues. Although in vitro studies have suggested
      various roles for TEAD proteins, their in vivo functions remain poorly
      understood. Here we examined the role of Tead genes by generating mouse mutants
      for Tead1 and Tead2. Tead2(-/-) mice appeared normal, but Tead1(-/-); Tead2(-/-)
      embryos died at embryonic day 9.5 (E9.5) with severe growth defects and
      morphological abnormalities. At E8.5, Tead1(-/-); Tead2(-/-) embryos were already
      small and lacked characteristic structures such as a closed neural tube, a
      notochord, and somites. Despite these overt abnormalities, differentiation and
      patterning of the neural plate and endoderm were relatively normal. In contrast,
      the paraxial mesoderm and lateral plate mesoderm were displaced laterally, and a
      differentiated notochord was not maintained. These abnormalities and defects in
      yolk sac vasculature organization resemble those of mutants for Yap, which
      encodes a coactivator of TEAD proteins. Moreover, we demonstrated genetic
      interactions between Tead1 and Tead2 and Yap. Finally, Tead1(-/-); Tead2(-/-)
      embryos showed reduced cell proliferation and increased apoptosis. These results
      suggest that Tead1 and Tead2 are functionally redundant, use YAP as a major
      coactivator, and support notochord maintenance as well as cell proliferation and
      survival in mouse development.

PMID- 18332128
TI  - Regulation of the Drosophila hypoxia-inducible factor alpha Sima by CRM1
      dependent nuclear export.
AB  - Hypoxia-inducible factor alpha (HIF-alpha) proteins are regulated by oxygen
      levels through several different mechanisms that include protein stability,
      transcriptional coactivator recruitment, and subcellular localization. It was
      previously reported that these transcription factors are mainly nuclear in
      hypoxia and cytoplasmic in normoxia, but so far the molecular basis of this
      regulation is unclear. We show here that the Drosophila melanogaster HIF-alpha
      protein Sima shuttles continuously between the nucleus and the cytoplasm. We
      identified the relevant nuclear localization signal and two functional nuclear
      export signals (NESs). These NESs are in the Sima basic helix-loop-helix (bHLH)
      domain and promote CRM1-dependent nuclear export. Site-directed mutagenesis of
      either NES provoked Sima nuclear retention and increased transcriptional
      activity, suggesting that nuclear export contributes to Sima regulation. The
      identified NESs are conserved and probably functional in the bHLH domains of
      several bHLH-PAS proteins. We propose that rapid nuclear export of Sima regulates
      the duration of cellular responses to hypoxia.

PMID- 18332130
TI  - Identification of novel isoforms of mouse L-selectin with different carboxyl
      terminal tails.
AB  - The leukocyte adhesion molecule L-selectin mediates the recruitment of
      lymphocytes to secondary lymphoid organs and is involved in the accumulation of
      neutrophils at sites of inflammation. In this study, we report the identification
      of novel isoforms of the mouse L-selectin gene, termed L-selectin-v1 and L
      selectin-v2. Sequence analysis revealed that these isoforms are generated by
      alternative splicing: the L-selectin-v2 transcript includes a previously unknown
      exon of 100 bp located between the 7th and 8th exons of the mouse L-selectin
      gene, while the L-selectin-v1 transcript contains the first 49-bp sequence of
      this new exon. The insertion of each new sequence adds a downstream reading
      frame, giving rise to predicted proteins that differ in their carboxyl-terminal
      tails. These splice variants were found in cells that express conventional L
      selectin, termed L-selectin-c, including B and T lymphocytes and granulocytes.
      Functionally, like L-selectin-c, both L-selectin-v1 and L-selectin-v2 expressed
      in cultured cells underwent phorbol ester-induced shedding, although L-selectin
      v1 and L-selectin-v2 were shed to a greater and lesser degree, respectively, than
      L-selectin-c. Under flow conditions, both L-selectin-v1 and L-selectin-v2
      mediated faster cell rolling than did L-selectin-c. In addition, ligation of L
      selectin-c and L-selectin-v1, but not L-selectin-v2, induced p38 mitogen
      activated protein kinase phosphorylation. These results suggest that alternative
      splicing is one mechanism for generating functional diversity in L-selectin.

PMID- 18332129
TI  - Design of an active ultrastable single-chain insulin analog: synthesis,
      structure, and therapeutic implications.
AB  - Single-chain insulin (SCI) analogs provide insight into the inter-relation of
      hormone structure, function, and dynamics. Although compatible with wild-type
      structure, short connecting segments (<3 residues) prevent induced fit upon
      receptor binding and so are essentially without biological activity. Substantial
      but incomplete activity can be regained with increasing linker length. Here, we
      describe the design, structure, and function of a single-chain insulin analog
      (SCI-57) containing a 6-residue linker (GGGPRR). Native receptor-binding affinity
      (130 +/- 8% relative to the wild type) is achieved as hindrance by the linker is
      offset by favorable substitutions in the insulin moiety. The thermodynamic
      stability of SCI-57 is markedly increased (DeltaDeltaG(u) = 0.7 +/- 0.1 kcal/mol
      relative to the corresponding two-chain analog and 1.9 +/- 0.1 kcal/mol relative
      to wild-type insulin). Analysis of inter-residue nuclear Overhauser effects
      demonstrates that a native-like fold is maintained in solution. Surprisingly, the
      glycine-rich connecting segment folds against the insulin moiety: its central Pro
      contacts Val(A3) at the edge of the hydrophobic core, whereas the final Arg
      extends the A1-A8 alpha-helix. Comparison between SCI-57 and its parent two-chain
      analog reveals striking enhancement of multiple native-like nuclear Overhauser
      effects within the tethered protein. These contacts are consistent with wild-type
      crystal structures but are ordinarily attenuated in NMR spectra of two-chain
      analogs, presumably due to conformational fluctuations. Linker-specific damping
      of fluctuations provides evidence for the intrinsic flexibility of an insulin
      monomer. In addition to their biophysical interest, ultrastable SCIs may enhance
      the safety and efficacy of insulin replacement therapy in the developing world.

PMID- 18332131
TI  - Annexin A2 interactions with Rab14 in alveolar type II cells.
AB  - Annexin A2, a calcium-dependent phospholipid-binding protein, is abundantly
      expressed in alveolar type II cells where it plays a role in lung surfactant
      secretion. Nevertheless, little is known about the details of its cellular
      pathways. To identify annexin A2-regulated or associated proteins, we silenced
      endogenous annexin A2 expression in rat alveolar type II cells by RNA
      interference and assessed the change of the cellular transcriptome by DNA
      microarray analysis. The loss of annexin A2 resulted in the change of 61 genes.
      Thirteen of the selected genes (11 down-regulated and 2 up-regulated genes) were
      validated by real time quantitative PCR. When the loss of rat annexin A2 was
      rescued by overexpressing EGFP-tagged human annexin A2, six of seven selected
      targets returned to their normal expression level, indicating that these genes
      are indeed annexin A2-associated targets. One of the targets, Rab14, co
      immunoprecipitated with annexin A2. Rab14 also co-localized in part with annexin
      A2 and lamellar bodies in alveolar type II cells. The silencing of Rab14 resulted
      in a decrease in surfactant secretion, suggesting that Rab14 may play a role in
      surfactant secretion.

PMID- 18332132
TI  - Subunit a facilitates aqueous access to a membrane-embedded region of subunit c
      in Escherichia coli F1F0 ATP synthase.
AB  - Rotary catalysis in F(1)F(0) ATP synthase is powered by proton translocation
      through the membrane-embedded F(0) sector. Proton binding and release occurs in
      the middle of the membrane at Asp-61 on transmembrane helix 2 of subunit c.
      Previously, the reactivity of cysteines substituted into F(0) subunit a revealed
      two regions of aqueous access, one extending from the periplasm to the middle of
      the membrane and a second extending from the middle of the membrane to the
      cytoplasm. To further characterize aqueous accessibility at the subunit a-c
      interface, we have substituted Cys for residues on the cytoplasmic side of
      transmembrane helix 2 of subunit c and probed the accessibility to these
      substituted positions using thiolate-reactive reagents. The Cys substitutions
      tested were uniformly inhibited by Ag(+) treatment, which suggested widespread
      aqueous access to this generally hydrophobic region. Sensitivity to N
      ethylmaleimide (NEM) and methanethiosulfonate reagents was localized to a
      membrane-embedded pocket surrounding Asp-61. The cG58C substitution was
      profoundly inhibited by all the reagents tested, including membrane impermeant
      methanethiosulfonate reagents. Further studies of the highly reactive cG58C
      substitution revealed that NEM modification of a single c subunit in the
      oligomeric c-ring was sufficient to cause complete inhibition. In addition, NEM
      modification of subunit c was dependent upon the presence of subunit a. The
      results described here provide further evidence for an aqueous-accessible region
      at the interface of subunits a and c extending from the middle of the membrane to
      the cytoplasm.

PMID- 18332133
TI  - Functional characterization of murine interferon regulatory factor 5 (IRF-5) and
      its role in the innate antiviral response.
AB  - Although the role of human IRF-5 in antiviral and inflammatory responses in vitro
      has been well characterized, much remains to be elucidated about murine IRF-5.
      Murine IRF-5, unlike the heavily spliced human gene, is primarily expressed as a
      full-length transcript, with only a single splice variant that was detected in
      very low levels in the bone marrow of C57BL/6J mice. This bone marrow variant
      contains a 288-nucleotide deletion from exons 4-6 and exhibits impaired
      transcriptional activity. The murine IRF-5 can be activated by both TBK1 and
      MyD88 to form homodimers and bind to and activate transcription of type I
      interferon and inflammatory cytokine genes. The importance of IRF-5 in the
      antiviral and inflammatory response in vivo is highlighted by marked reductions
      in serum levels of type I interferon and tumor necrosis factor alpha (TNFalpha)
      in Newcastle disease virus-infected Irf5(-)(/)(-) mice. IRF-5 is critical for
      TLR3-, TLR4-, and TLR9-dependent induction of TNFalpha in CD11c(+) dendritic
      cells. In contrast, TLR9, but not TLR3/4-mediated induction of type I IFN
      transcription, is dependent on IRF-5 in these cells. In addition, IRF-5 regulates
      TNFalpha but not type I interferon gene transcription in Newcastle disease virus
      infected peritoneal macrophages. Altogether, these data reveal the cell type
      specific importance of IRF-5 in MyD88-mediated antiviral pathways and the
      widespread role of IRF-5 in the regulation of inflammatory cytokines.

PMID- 18332135
TI  - Calcium ions are involved in the unusual red shift of the light-harvesting 1 Qy
      transition of the core complex in thermophilic purple sulfur bacterium
      Thermochromatium tepidum.
AB  - Thermophilic purple sulfur bacterium, Thermochromatium tepidum, can grow at
      temperatures up to 58 degrees C and exhibits an unusual Qy absorption at 915 nm
      for the core light-harvesting complex (LH1), an approximately 35-nm red shift
      from those of its mesophilic counterparts. We demonstrate in this study, using a
      highly purified LH1-reaction center complex, that the LH1 Qy transition is
      strongly dependent on metal cations and Ca2+ is involved in the unusual red
      shift. Removal of the Ca2+ resulted in formation of a species with the LH1 Qy
      absorption at 880 nm, and addition of the Ca2+ to the 880-nm species recovered
      the native 915-nm form. Interchange between the two forms is fully reversible.
      Based on spectroscopic and isothermal titration calorimetry analyses, the Ca2+
      binding to the LH1 complex was estimated to occur in a stoichiometric ratio of
      Ca2+/alphabeta-subunit = 1:1 and the binding constant was in 10(5) m(-1) order of
      magnitude, which is comparable with those for EF-hand Ca2+-binding proteins.
      Despite the high affinity, conformational changes in the LH1 complex upon Ca2+
      binding were small and occurred slowly, with a typical time constant of
      approximately 6 min. Replacement of the Ca2+ with other metal cations caused blue
      shifts of the Qy bands depending on the property of the cations, indicating that
      the binding site is highly selective. Based on the amino acid sequences of the
      LH1 complex, possible Ca2+-binding sites are proposed that consist of several
      acidic amino acid residues near the membrane interfaces of the C-terminal region
      of the alpha-polypeptide and the N-terminal region of the beta-polypeptide.

PMID- 18332134
TI  - Protein kinase D-dependent phosphorylation and nuclear export of histone
      deacetylase 5 mediates vascular endothelial growth factor-induced gene expression
      and angiogenesis.
AB  - Vascular endothelial growth factor (VEGF) is essential for normal and
      pathological angiogenesis. However, the signaling pathways linked to gene
      regulation in VEGF-induced angiogenesis are not fully understood. Here we
      demonstrate a critical role of protein kinase D (PKD) and histone deacetylase 5
      (HDAC5) in VEGF-induced gene expression and angiogenesis. We found that VEGF
      stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through
      a VEGF receptor 2-phospholipase Cgamma-protein kinase C-PKD-dependent pathway. We
      further showed that the PKD-HDAC5 pathway mediated myocyte enhancer factor-2
      transcriptional activation and a specific subset of gene expression in response
      to VEGF, including NR4A1, an orphan nuclear receptor involved in angiogenesis.
      Specifically, inhibition of PKD by overexpression of the PKD kinase-negative
      mutant prevents VEGF-induced HDAC5 phosphorylation and nuclear export as well as
      NR4A1 induction. Moreover, a mutant of HDAC5 specifically deficient in PKD
      dependent phosphorylation inhibited VEGF-mediated NR4A1 expression, endothelial
      cell migration, and in vitro angiogenesis. These findings suggest that the PKD
      HDAC5 pathway plays an important role in VEGF regulation of gene transcription
      and angiogenesis.

PMID- 18332136
TI  - Biosynthetic exchange of bromide for chloride and strontium for calcium in the
      photosystem II oxygen-evolving enzymes.
AB  - The active site for water oxidation in photosystem II goes through five
      sequential oxidation states (S(0) to S(4)) before O(2) is evolved. It consists of
      a Mn(4)Ca cluster close to a redox-active tyrosine residue (Tyr(Z)). Cl(-) is
      also required for enzyme activity. To study the role of Ca(2+) and Cl(-) in PSII,
      these ions were biosynthetically substituted by Sr(2+) and Br(-), respectively,
      in the thermophilic cyanobacterium Thermosynechococcus elongatus. Irrespective of
      the combination of the non-native ions used (Ca/Br, Sr/Cl, Sr/Br), the enzyme
      could be isolated in a state that was fully intact but kinetically limited. The
      electron transfer steps affected by the exchanges were identified and then
      investigated by using time-resolved UV-visible absorption spectroscopy, time
      resolved O(2) polarography, and thermoluminescence spectroscopy. The effect of
      the Ca(2+)/Sr(2+) and Cl(-)/Br(-) exchanges was additive, and the magnitude of
      the effect varied in the following order: Ca/Cl < Ca/Br < Sr/Cl < Sr/Br. In all
      cases, the rate of O(2) release was similar to that of the S(3)Tyr(Z)(.) to
      S(0)Tyr(Z) transition, with the slowest kinetics (i.e. the Sr/Br enzyme) being
      approximately 6-7 slower than in the native Ca/Cl enzyme. This slowdown in the
      kinetics was reflected in a decrease in the free energy level of the S(3) state
      as manifest by thermoluminescence. These observations indicate that Cl(-) is
      involved in the water oxidation mechanism. The possibility that Cl(-) is close to
      the active site is discussed in terms of recent structural models.

PMID- 18332137
TI  - Tumor suppressor cylindromatosis acts as a negative regulator for Streptococcus
      pneumoniae-induced NFAT signaling.
AB  - Gram-positive bacterium Streptococcus pneumoniae is an important human pathogen
      that colonizes the upper respiratory tract and is also the major cause of
      morbidity and mortality worldwide. S. pneumoniae causes invasive diseases such as
      pneumonia, meningitis, and otitis media. Despite the importance of pneumococcal
      diseases, little is known about the molecular mechanisms by which S. pneumoniae
      induced inflammation is regulated, especially the negative regulatory mechanisms.
      Here we show that S. pneumoniae activates nuclear factor of activated T cells
      (NFAT) signaling pathway and the subsequent up-regulation of inflammatory
      mediators via a key pneumococcal virulence factor, pneumolysin. We also
      demonstrate that S. pneumoniae activates NFAT transcription factor independently
      of Toll-like receptors 2 and 4. Moreover, S. pneumoniae induces NFAT activation
      via both Ca(2+)-calcineurin and transforming growth factor-beta-activated kinase
      1 (TAK1)-mitogen-activated protein kinase kinase (MKK) 3/6-p38alpha/beta
      dependent signaling pathways. Interestingly, we found for the first time that
      tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for S.
      pneumoniae-induced NFAT signaling pathway via a deubiquitination-dependent
      mechanism. Finally, we showed that CYLD interacts with and deubiquitinates TAK1
      to negatively regulate the activation of the downstream MKK3/6-p38alpha/beta
      pathway. Our studies thus bring new insights into the molecular pathogenesis of
      S. pneumoniae infections through the NFAT-dependent mechanism and further
      identify CYLD as a negative regulator for NFAT signaling, thereby opening up new
      therapeutic targets for these diseases.

PMID- 18332138
TI  - Synergistic collagenase expression and cartilage collagenolysis are
      phosphatidylinositol 3-kinase/Akt signaling-dependent.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway has emerged as a major
      regulator of cellular functions and has been implicated in several pathologies
      involving remodeling of extracellular matrix (ECM). The end stage of inflammatory
      joint diseases is characterized by excessive ECM catabolism, and in this study we
      assess the role of PI3K signaling in the induction of collagenolytic matrix
      metalloproteinases (MMPs) in human chondrocytes. We used the most potent cytokine
      stimulus reported to promote cartilage ECM catabolism, namely interleukin-1 (IL
      1) in combination with oncostatin M (OSM). Both OSM and IL-6 (in the presence of
      its soluble receptor), but not IL-1 nor leukemia inhibitory factor, induced Akt
      phosphorylation in human chondrocytes. Inhibition of PI3K signaling using
      LY294002 blocked IL-1+OSM-mediated Akt phosphorylation, induction of MMP-1 and
      MMP-13, and cartilage collagenolysis. To further explore the role of downstream
      substrates within the PI3K pathway, complementary use of small molecule
      inhibitors and specific small interfering RNAs demonstrated that the PI3K subunit
      p110alpha and Akt1 were required for MMP-1 mRNA induction. MMP-13 induction was
      also reduced by loss of function of these molecules and by a lack of p110delta, 3
      phosphoinositide-dependent kinase-1 or Akt3. We therefore propose that the
      activities of specific elements of the PI3K signaling pathway, including Akt, are
      necessary for the synergistic induction of MMP-1 and MMP-13 and the cartilage
      breakdown stimulated by IL-1+OSM. Our data provide new insight into the mechanism
      of synergy between IL-1 and OSM and highlight new therapeutic targets for
      inflammatory joint diseases that aim to repress the expression of collagenases.

PMID- 18332139
TI  - Role of cadherin-mediated cell-cell adhesion in pancreatic exocrine-to-endocrine
      transdifferentiation.
AB  - Although pancreatic exocrine acinar cells have the potential to
      transdifferentiate into pancreatic endocrine cells, the mechanisms are poorly
      understood. Here we report that intracellular signaling pathways, including those
      involving MAPK and phosphatidylinositol 3 (PI3)-kinase, are activated by
      enzymatic dissociation of pancreatic acinar cells and that spherical cell
      clusters are formed by cadherin-mediated cell-cell adhesion during
      transdifferentiation. Inhibition of PI3-kinase by LY294002 prevents spheroid
      formation by degrading E-cadherin and beta-catenin, blocking transdifferentiation
      into insulin-secreting cells. In addition, neutralizing antibody against E
      cadherin suppresses the induction of genes characteristic of pancreatic beta
      cells. We also show that loss of cadherin-mediated cell-cell adhesion induces and
      maintains a dedifferentiated state in isolated pancreatic acinar cells. Thus,
      disruption and remodeling of cadherin-mediated cell-cell adhesion is critical in
      pancreatic exocrine-to-endocrine transdifferentiation, in which the PI3-kinase
      pathway plays an essential role.

PMID- 18332140
TI  - NOTCH1 up-regulation and signaling involved in Mycobacterium bovis BCG-induced
      SOCS3 expression in macrophages.
AB  - Suppressor of cytokine signaling (SOCS) 3 is a critical negative regulator of
      cytokine signaling and is induced by Mycobacterium bovis Bacille Calmette-Guerin
      (M. bovis BCG) in mouse macrophages. However, little is known about the early
      receptor proximal signaling mechanisms underlying mycobacteria-mediated induction
      of SOCS3. We demonstrate here for the first time that M. bovis BCG up-regulates
      NOTCH1 and activates the NOTCH1 signaling pathway, leading to the expression of
      SOCS3. We show that perturbing Notch signaling in infected macrophages results in
      the marked reduction in the expression of SOCS3. Furthermore, enforced expression
      of the Notch1 intracellular domain in RAW 264.7 macrophages induces the
      expression of SOCS3, which can be further potentiated by M. bovis BCG. The
      perturbation of Toll-like receptor (TLR) 2 signaling resulted in marked reduction
      in SOCS3 levels and expression of the NOTCH1 target gene, Hes1. The down
      regulation of MyD88 resulted in a significant decrease in SOCS3 expression,
      implicating the role of the TLR2-MyD88 axis in M. bovis BCG-triggered signaling.
      However, the SOCS3 inducing ability of M. bovis BCG remains unaltered also upon
      infection of macrophages from TLR4-defective C3H/HeJ mice. More importantly,
      signaling perturbation data suggest the involvement of cross-talk among members
      of the phosphoinositide 3-kinase and mitogen-activated protein kinase cascades
      with NOTCH1 signaling in SOCS3 expression. Furthermore, SOCS3 expression requires
      the NOTCH1-mediated recruitment of Suppressor of Hairless (CSL) and nuclear
      factor-kappaB to the Socs3 promoter. Overall, these results implicate NOTCH1
      signaling during inducible expression of SOCS3 following infection of macrophages
      with an intracellular bacillus-like M. bovis BCG.

PMID- 18332141
TI  - Manganese binding to the prion protein.
AB  - There is considerable evidence that the prion protein binds copper. However,
      there have also been suggestions that prion protein (PrP) binds manganese. We
      used isothermal titration calorimetry to identify the manganese binding sites in
      wild-type mouse PrP. The protein showed two manganese binding sites with
      affinities that would bind manganese at concentrations of 63 and 200 mum at pH
      5.5. This indicates that PrP binds manganese with affinity similar to other known
      manganese-binding proteins. Further study indicated that the main manganese
      binding site is associated with His-95 in the so-called "fifth site" normally
      associated with copper binding. Additionally, it was shown that occupancy by
      copper does not prevent manganese binding. Under these conditions, manganese
      binding resulted in an altered conformation of PrP, displacement of copper, and
      altered redox chemistry of the metal-protein complex. Cyclic voltammetric
      measurements suggested a complex redox chemistry involving manganese bound to
      PrP, whereas copper-bound PrP was able to undergo fully reversible electron
      cycling. Additionally, manganese binding to PrP converted it to a form able to
      catalyze aggregation of metal-free PrP. These results further support the notion
      that manganese binding could cause a conformation change in PrP and trigger
      changes in the protein similar to those associated with prion disease.

PMID- 18332142
TI  - Structural and thermodynamic analyses of solute-binding Protein from
      Bifidobacterium longum specific for core 1 disaccharide and lacto-N-biose I.
AB  - Recently, a gene cluster involving a phosphorylase specific for lacto-N-biose I
      (LNB; Galbeta1-3GlcNAc) and galacto-N-biose (GNB; Galbeta1-3GalNAc) has been
      found in Bifidobacterium longum. We showed that the solute-binding protein of a
      putative ATP-binding cassette-type transporter encoded in the cluster
      crystallizes only in the presence of LNB or GNB, and therefore we named it
      GNB/LNB-binding protein (GL-BP). Isothermal titration calorimetry measurements
      revealed that GL-BP specifically binds LNB and GNB with K(d) values of 0.087 and
      0.010 microm, respectively, and the binding process is enthalpy-driven. The
      crystal structures of GL-BP complexed with LNB, GNB, and lacto-N-tetraose
      (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) were determined. The interactions between
      GL-BP and the disaccharide ligands mainly occurred through water-mediated
      hydrogen bonds. In comparison with the LNB complex, one additional hydrogen bond
      was found in the GNB complex. These structural characteristics of ligand binding
      are in agreement with the thermodynamic properties. The overall structure of GL
      BP was similar to that of maltose-binding protein; however, the mode of ligand
      binding and the thermodynamic properties of these proteins were significantly
      different.

PMID- 18332143
TI  - Analysis of nucleotide binding to P97 reveals the properties of a tandem AAA
      hexameric ATPase.
AB  - p97, an essential chaperone in endoplasmic reticulum-associated degradation and
      organelle biogenesis, contains two AAA domains (D1 and D2) and assembles as a
      stable hexamer. We present a quantitative analysis of nucleotide binding to both
      D1 and D2 domains of p97, the first detailed study of nucleotide binding to both
      AAA domains for this type of AAA+ ATPase. We report that adenosine 5'-O
      (thiotriphosphate) (ATPgammaS) binds with similar affinity to D1 and D2, but ADP
      binds with higher affinity to D1 than D2, offering an explanation for the higher
      ATPase activity in D2. Stoichiometric measurements suggest that although both ADP
      and ATPgammaS can saturate all 6 nucleotide binding sites in D1, only 3-4 of the
      6 D2 sites can bind ATPgammaS simultaneously. ATPgammaS binding triggers a
      downstream cooperative conformational change of at least three monomers, which
      involves conserved arginine fingers and is necessary for ATP hydrolysis.

PMID- 18332144
TI  - Caveolin-1 up-regulation during epithelial to mesenchymal transition is mediated
      by focal adhesion kinase.
AB  - Emerging evidence has shown that caveolin-1 is up-regulated in a number of
      metastatic cancers and can influence various aspects of cell migration. However,
      in general, the role of caveolin-1 in cancer progression is poorly understood. In
      the present study, we examined alterations in caveolin-1 expression during
      epithelial-to-mesenchymal transition (EMT) and the ability of caveolin-1 to alter
      cancer cell adhesion, an aspect of cell motility. We employed two EMT cell
      models, the human embryonic carcinoma cell line NT2/D1, and TGF-beta1-treated
      NMuMG cells, which are derived from normal mouse mammary epithelia. Caveolin-1
      expression was substantially up-regulated in both cell lines following the
      induction of EMT and was preceded by increased activation of focal adhesion
      kinase (FAK) and Src, two known tyrosine kinases involved in EMT. We hypothesized
      that caveolin-1 expression could be influenced by increased FAK phosphorylation,
      to which Src is a known contributor. Examination of FAK+/+ and FAK-/- mouse
      embryonic fibroblasts revealed that in cells devoid of FAK, caveolin-1 expression
      is strikingly diminished. Using FAK and superFAK constructs and the novel FAK
      inhibitor PF-228, we were able to demonstrate that indeed, FAK can regulate
      caveolin-1 expression. We also found that Src can contribute to increases in
      caveolin-1 expression, however, only in the presence of FAK. From the culmination
      of this data and our functional analyses, we conclude that caveolin-1 expression
      can be up-regulated during EMT, and further, once expressed, caveolin-1 can
      greatly influence cancer cell adhesion.

PMID- 18332146
TI  - Biochemical and structural insights into bacterial organelle form and biogenesis.
AB  - Many heterotrophic bacteria have the ability to make polyhedral structures
      containing metabolic enzymes that are bounded by a unilamellar protein shell
      (metabolosomes or enterosomes). These bacterial organelles contain enzymes
      associated with a specific metabolic process (e.g. 1,2-propanediol or
      ethanolamine utilization). We show that the 21 gene regulon specifying the pdu
      organelle and propanediol utilization enzymes from Citrobacter freundii is fully
      functional when cloned in Escherichia coli, both producing metabolosomes and
      allowing propanediol utilization. Genetic manipulation of the level of specific
      shell proteins resulted in the formation of aberrantly shaped metabolosomes,
      providing evidence for their involvement as delimiting entities in the organelle.
      This is the first demonstration of complete recombinant metabolosome activity
      transferred in a single step and supports phylogenetic evidence that the pdu
      genes are readily horizontally transmissible. One of the predicted shell proteins
      (PduT) was found to have a novel Fe-S center formed between four protein
      subunits. The recombinant model will facilitate future experiments establishing
      the structure and assembly of these multiprotein assemblages and their fate when
      the specific metabolic function is no longer required.

PMID- 18332145
TI  - IMP modulates KSR1-dependent multivalent complex formation to specify ERK1/2
      pathway activation and response thresholds.
AB  - The Ras effector and ubiquitin-protein isopeptide ligase family member IMP acts
      as a steady-state resistor within the Raf-MEK-ERK kinase module. IMP
      concentrations are regulated by Ras through induction of autodegradation and can
      modulate signal/response thresholds by directly limiting the assembly of
      functional KSR1-dependent Raf.MEK complexes. Here, we show that the capacity of
      IMP to inhibit signal propagation through Raf to MEK is a consequence of
      disrupting KSR1 homooligomerization and B-Raf/c-Raf hetero-oligomerization. This
      impairs both the recruitment of MEK to activated Raf family members and the
      contribution of Raf oligomers to c-Raf kinase activation. Our observations
      indicate that human KSR1 proteins promote assembly of multivalent Raf.MEK
      complexes that are required for c-Raf kinase activation and functional coupling
      of active kinases to downstream substrates. This property is engaged by IMP for
      modulation of signal amplitude.

PMID- 18332147
TI  - Processing and nuclear localization of CRMP2 during brain development induce
      neurite outgrowth inhibition.
AB  - Collapsin response mediator proteins (CRMPs) are believed to play a crucial role
      in neuronal differentiation and axonal outgrowth. Among them, CRMP2 mediates
      axonal guidance by collapsing growth cones during development. This activity is
      correlated with the reorganization of cytoskeletal proteins. CRMP2 is implicated
      in the regulation of several intracellular signaling pathways. Two subtypes, A
      and B, and multiple cytosolic isoforms of CRMP2B with apparent masses between 62
      and 66 kDa have previously been reported. Here, we show a new short isoform of 58
      kDa, expressed during brain development, derived from C-terminal processing of
      the CRMP2B subtype. Although full-length CRMP2 is restricted to the cytoplasm,
      using transfection experiments, we demonstrate that a part of the short isoform
      is found in the nucleus. Interestingly, at the tissue level, this short CRMP2 is
      also found in a nuclear fraction of brain extract. By mutational analysis, we
      demonstrate, for the first time, that nuclear translocation occurs via nuclear
      localization signal (NLS) within residues Arg(471)-Lys(472) in CRMP2 sequence.
      The NLS may be unmasked after C-terminal processing; thereby, this motif may be
      surface-exposed. This short CRMP2 induces neurite outgrowth inhibition in
      neuroblastoma cells and suppressed axonal growth in cultured cortical neurons,
      whereas full-length CRMP2 promotes neurite elongation. The NLS-mutated short
      isoform, restricted to the cytoplasm, abrogates both neurite outgrowth and axon
      growth inhibition, indicating that short nuclear CRMP2 acts as a dominant signal.
      Therefore, post-transcriptional processing of CRMP2 together with its nuclear
      localization may be an important key in the regulation of neurite outgrowth in
      brain development.

PMID- 18332148
TI  - CD36 mediates both cellular uptake of very long chain fatty acids and their
      intestinal absorption in mice.
AB  - The intestine has an extraordinary capacity for fatty acid (FA) absorption.
      Numerous candidates for a protein-mediated mechanism of dietary FA absorption
      have been proposed, but firm evidence for this process has remained elusive. Here
      we show that the scavenger receptor CD36 is required both for the uptake of very
      long chain FAs (VLCFAs) in cultured cells and the absorption of dietary VLCFAs in
      mice. We found that the fraction of CD36-dependent saturated fatty acid
      association/absorption in these model systems is proportional to the FA chain
      length and specific for fatty acids and fatty alcohols containing very long
      saturated acyl chains. Moreover, intestinal VLCFA absorption is completely
      abolished in CD36-null mice fed a high fat diet, illustrating that the
      predominant mechanism for VLCFA absorption is CD36-dependent. Together, these
      findings represent the first direct evidence for protein-facilitated FA
      absorption in the intestine and identify a novel therapeutic target for the
      treatment of diseases characterized by elevated VLCFA levels.

PMID- 18332149
TI  - The crystal structure of the human toll-like receptor 10 cytoplasmic domain
      reveals a putative signaling dimer.
AB  - The Toll/interleukin-1 receptor (TIR) domain is a highly conserved signaling
      domain found in the intracellular regions of Toll-like receptors (TLRs), in
      interleukin-1 receptors, and in several cytoplasmic adaptor proteins. TIR domains
      mediate receptor signal transduction through recruitment of adaptor proteins and
      play critical roles in the innate immune response and inflammation. This work
      presents the 2.2A crystal structure of the TIR domain of human TLR10, revealing a
      symmetric dimer in the asymmetric unit. The dimer interaction surface contains
      residues from the BB-loop, DD-loop, and alphaC-helix, which have previously been
      identified as important structural motifs for signaling in homologous TLR
      receptors. The interaction surface is extensive, containing a central hydrophobic
      patch surrounded by polar residues. The BB-loop forms a tight interaction, where
      a range of consecutive residues binds in a pocket formed by the reciprocal BB
      loop and alphaC-helix. This pocket appears to be well suited for binding peptide
      substrates, which is consistent with the notion that peptides and peptide
      mimetics of the BB-loop are inhibitors for TLR signaling. The TLR10 structure is
      in good agreement with available biochemical data on TLR receptors and is likely
      to provide a good model for the physiological dimer.

PMID- 18332150
TI  - Kids Identifying and Defeating Stroke (KIDS): development and implementation of a
      multiethnic health education intervention to increase stroke awareness among
      middle school students and their parents.
AB  - The Kids Identifying and Defeating Stroke (KIDS) project is a 3-year prospective,
      randomized, controlled, multiethnic school-based intervention study. Project
      goals include increasing knowledge of stroke signs and treatment and intention to
      immediately call 911 among Mexican American (MA) and non-Hispanic White (NHW)
      middle school students and their parents. This article describes the design,
      implementation, and interim evaluation of this theory-based intervention.
      Intervention students received a culturally appropriate stroke education program
      divided into four 50-minute classes each year during the sixth, seventh, and
      eighth grades. Each class session also included a homework assignment that
      involved the students' parents or other adult partners. Interim-test results
      indicate that this educational intervention was successful in improving students'
      stroke symptom and treatment knowledge and intent to call 911 upon witnessing a
      stroke compared with controls. The authors conclude that this school-based
      educational intervention to reduce delay time to hospital arrival for stroke
      shows early promise.

PMID- 18332151
TI  - Metabolic phenotype in the brothers of women with polycystic ovary syndrome.
AB  - OBJECTIVE: Hyperandrogenemia, insulin resistance, and dyslipidemia demonstrate
      familial aggregation in the female first-degree relatives of women with
      polycystic ovary syndrome (PCOS), suggesting that these defects are heritable.
      Hyperandrogenemia also appears to be the male reproductive phenotype. We
      performed this study to test the hypothesis that brothers of women with PCOS have
      metabolic defects similar to those of their proband sisters. RESEARCH DESIGN AND
      METHODS: This was a prospective case-control study performed at four academic
      medical centers in the U.S. Fasting blood was obtained from 196 non-Hispanic
      white brothers of women with PCOS and 169 control men of age, BMI, and ethnicity
      comparable to those of brothers. A separate analysis was performed by study site
      to assess potential regional variations in metabolic parameters. RESULTS:
      Overall, brothers of women with PCOS had significantly higher total (P = 0.001)
      and LDL cholesterol (P = 0.01) as well as triglyceride levels (P = 0.01) compared
      with control men, although there were regional variations in these differences.
      There were significant positive correlations between brothers and their sisters
      with PCOS for total (rho = 0.2, P = 0.009) and LDL cholesterol (rho = 0.3, P =
      0.001) and triglyceride (rho = 0.2, P = 0.05) levels. Brothers also had
      significantly higher fasting insulin levels and homeostatic index of insulin
      resistance (P = 0.02 for both comparisons) compared with control men.
      CONCLUSIONS: Brothers of women with PCOS have dyslipidemia as well as evidence
      for insulin resistance similar to that of their proband sisters with PCOS. These
      findings are consistent with the hypothesis that some metabolic abnormalities in
      PCOS are heritable and are not sex specific.

PMID- 18332152
TI  - Plantar fascia thickness, a measure of tissue glycation, predicts the development
      of complications in adolescents with type 1 diabetes.
AB  - OBJECTIVE: Direct measurement of collagen glycation requires skin biopsy, which
      is invasive. We hypothesized that measurement of plantar fascia thickness (PFT)
      by ultrasound is an alternative index of tissue glycation and a marker of
      microvascular disease. RESEARCH DESIGN AND METHODS: This was a prospective
      longitudinal study of microvascular complications in 344 adolescents with type 1
      diabetes, whose PFT was assessed by ultrasound at baseline. Retinopathy was
      assessed by seven-field fundal photography, albumin excretion rate (AER) measured
      from three consecutive timed overnight urine specimens, autonomic neuropathy by
      pupillometry and cardiovascular tests, and peripheral neuropathy by vibration and
      thermal thresholds. Longitudinal analysis was performed using generalized
      estimating equations with baseline PFT, duration, and A1C as explanatory
      variables. RESULTS: At first assessment, median (interquartile range) age was
      15.1 (13.5-17.2) years and diabetes duration was 8.5 (6.0-11.5) years. Median
      follow up was 3.2 (2.1-4.5) years with a median of 4 (2-13) complications
      assessments per patient. In multivariate analysis, baseline PFT (abnormal in 132
      subjects, 38%) predicted subsequent development of retinopathy (odds ratio 2.4
      [95% CI 1.1-5.0]), elevated AER (2.24 [1.05-5.11]), peripheral neuropathy (2.3
      [1.2-4.41]), and autonomic neuropathy (4.94 [2.46-9.91]). Limited joint mobility
      was present in only 4%. CONCLUSIONS: PFT is a significant predictor of the
      subsequent development of complications in type 1 diabetes, suggesting that
      glycation and oxidation of collagen in soft tissues may be independent risk
      factors for microvascular complications.

PMID- 18332153
TI  - Markers of endothelial dysfunction and inflammation in type 1 diabetic patients
      with or without diabetic nephropathy followed for 10 years: association with
      mortality and decline of glomerular filtration rate.
AB  - OBJECTIVE: We evaluated the association of biomarkers of endothelial dysfunction
      and inflammation with all-cause mortality and cardiovascular mortality and
      morbidity and decline in glomerular filtration rate (GFR) in type 1 diabetic
      patients. RESEARCH DESIGN AND METHODS: We prospectively followed 199 type 1
      diabetic patients with diabetic nephropathy and 192 patients with persistent
      normoalbuminuria. Biomarkers were measured at baseline. RESULTS: We constructed
      two Z scores: the mean inflammatory Z score combined C-reactive protein,
      interleukin-6, soluble intercellular adhesion molecule (sICAM-1), and secreted
      phospholipase A2 and the mean Z score for endothelial dysfunction combined
      soluble vascular cell adhesion molecule 1, plasminogen activator inhibitor-1, and
      sICAM-1. The mean Z score of inflammatory biomarkers was associated with
      mortality and the combined end point in patients with diabetic nephropathy after
      multivariate adjustment (hazard ratio 1.7 [95% CI 1.1-2.6]; P = 0.025 and 1.5
      [1.1-2.2]; P = 0.017). The mean Z score for endothelial dysfunction biomarkers
      was associated with mortality in a model adjusting for age and sex in patients
      with diabetic nephropathy (1.6 [1.0-2.3]; P = 0.031). The mean Z score for
      endothelial dysfunction correlated with decline in GFR (r = -0.243; P = 0.001);
      the correlation persisted after multivariate adjustment (coefficient -1.38 [95%
      CI -2.27 to -0.50]; P = 0.002). CONCLUSIONS: Mean Z scores of inflammatory
      biomarkers are significantly associated with all-cause mortality and
      cardiovascular morbidity and mortality in patients with nephropathy after
      multivariate adjustment. These data suggest that the high risk of cardiovascular
      disease in type 1 diabetes may be explained in part by inflammatory activity.
      Mean Z score of endothelial dysfunction correlated after multivariate adjustment
      with the rate of decline in GFR.

PMID- 18332155
TI  - Effect of race/ethnicity and persistent recognition of depression on mortality in
      elderly men with type 2 diabetes and depression.
AB  - OBJECTIVE: To determine whether mortality risk from depression among elderly men
      with type 2 diabetes differs by ethnicity and persistent recognition of
      depression. RESEARCH DESIGN AND METHODS: Data on a cohort of 14,500 male veterans
      with type 2 diabetes were analyzed. Diagnoses of depression and diabetes were
      based on ICD-9 codes. Persistent recognition was defined as an ICD-9 code for
      depression documented in at least the second or third visit after the initial
      diagnosis of depression. Hazards of death were compared using Cox proportional
      hazards regression models adjusting for relevant covariates. RESULTS: Over 10
      years, 2,305 deaths were documented. Mortality risk was higher for depressed than
      nondepressed veterans with diabetes (hazard ratio [HR] 1.6 [95% CI 1.3-1.8]).
      Among those with depression, mortality risk was lower with persistent recognition
      (0-2 visits vs. >or=3 visits after initial diagnosis, HR 0.58 [0.40-0.89]) but
      higher for whites than blacks (1.60 [1.11-2.31]). CONCLUSIONS: Increased
      mortality from depression differs by ethnicity and persistent recognition.

PMID- 18332154
TI  - Distinct component profiles and high risk among African Americans with metabolic
      syndrome: the Jackson Heart Study.
AB  - OBJECTIVE: Health of African Americans is seriously threatened by unremitting
      epidemics of diabetes and cardiovascular disease (CVD). However, the role of
      metabolic syndrome in the African-American population has not been investigated
      widely. This study examined the prevalence of metabolic syndrome and assessed its
      cross-sectional relationship to CVD in the Jackson Heart Study (JHS) cohort.
      RESEARCH DESIGN AND METHODS: A total of 5,302 participants aged >or=21 years who
      were recruited at baseline during 2000-2004 were analyzed for this study.
      Adjusted odds ratios (ORs) were estimated in a logistic regression analysis for
      coronary heart disease (CHD) and cerebrovascular disease (CBD) in those with and
      without coexisting metabolic syndrome. Diabetic participants were excluded.
      RESULTS: Among those aged 35-84 years, metabolic syndrome prevalence was 43.3% in
      women and 32.7% in men. Elevated blood pressure (70.4%), abdominal obesity
      (64.6%), and low HDL cholesterol (37.2%) were highly prevalent among those with
      metabolic syndrome. Prevalence rates for CVD, CHD, and CBD were 12.8, 8.7, and
      5.8%, respectively. After adjustment for age and sex, metabolic syndrome was
      associated with increased age- and sex-adjusted ORs for CVD (OR 1.7 [95% CI 1.4
      2.1]), CHD (1.7 [1.4-2.2]), and CBD (1.7 [1.3-2.3]) compared with those without
      CVD, CHD, or CBD. CONCLUSION: Metabolic syndrome prevalence in the JHS is among
      the highest reported for population-based cohorts worldwide and is significantly
      associated with increased ORs for CVD, CHD, and CBD. Abdominal obesity, increased
      blood pressure, and low HDL cholesterol (without triglyceride elevation) are
      surprisingly prominent. A high prevalence of low HDL emerges as a leading
      contributor to metabolic syndrome among African Americans in this large African
      American cohort.

PMID- 18332156
TI  - Markedly blunted metabolic effects of fructose in healthy young female subjects
      compared with male subjects.
AB  - OBJECTIVE: To compare the metabolic effects of fructose in healthy male and
      female subjects. RESEARCH DESIGN AND METHODS: Fasting metabolic profile and
      hepatic insulin sensitivity were assessed by means of a hyperglycemic clamp in 16
      healthy young male and female subjects after a 6-day fructose overfeeding.
      RESULTS: Fructose overfeeding increased fasting triglyceride concentrations by 71
      vs. 16% in male vs. female subjects, respectively (P < 0.05). Endogenous glucose
      production was increased by 12%, alanine aminotransferase concentration was
      increased by 38%, and fasting insulin concentrations were increased by 14% after
      fructose overfeeding in male subjects (all P < 0.05) but were not significantly
      altered in female subjects. Fasting plasma free fatty acids and lipid oxidation
      were inhibited by fructose in male but not in female subjects. CONCLUSIONS: Short
      term fructose overfeeding produces hypertriglyceridemia and hepatic insulin
      resistance in men, but these effects are markedly blunted in healthy young women.

PMID- 18332157
TI  - No apparent local effect of insulin on microdialysis continuous glucose-
      monitoring measurements.
AB  - OBJECTIVE: Data investigating the possible disturbing influence of insulin in the
      vicinity of continuous glucose monitoring (CGM) is lacking. We investigated the
      hypothesis that high local insulin concentrations would interfere with sensor
      readings. RESEARCH DESIGN AND METHODS: Two microdialysis sensors were inserted in
      the periumbilical region of 10 continuous subcutaneous insulin infusion (CSII)
      treated type 1 patients. A test sensor was inserted as close as possible to the
      insulin catheter and compared with a control sensor. Glucose peak and nadir were
      induced. Horizontal and vertical shifts were assessed using curve fitting, and
      mean absolute difference (MAD) between paired blood and sensor values were
      calculated. RESULTS: Curve fitting showed no significant differences between the
      two sensors. MAD +/- SD was 8.50 +/- 3.47% for the test sensor and 9.21 +/- 3.17%
      for the control sensor, P = 0.72. CONCLUSIONS: Microdialysis CGM can be
      accurately performed in the proximity of CSII systems.

PMID- 18332158
TI  - Long-term effects on medical costs of improving depression outcomes in patients
      with depression and diabetes.
AB  - OBJECTIVE: The purpose of this study was to examine the 5-year effects on total
      health care costs of the Pathways depression intervention program for patients
      with diabetes and comorbid depression compared with usual primary care. RESEARCH
      DESIGN AND METHODS: The Pathways Study was conducted in nine primary care
      practices of a large HMO and enrolled 329 patients with diabetes and comorbid
      major depression. The current study analyzed the differences in long-term medical
      costs between intervention and usual care patients. Participants were randomly
      assigned to a nurse depression intervention (n = 164) or to usual primary care (n
      = 165). The intervention included education about depression, behavioral
      activation, and a choice of either starting with support of antidepressant
      medication treatment by the primary care doctor or problem-solving therapy in
      primary care. Interventions were provided for up to 12 months, and the main
      outcome measures are health costs over a 5-year period. RESULTS: Patients in the
      intervention arm of the study had improved depression outcomes and trends for
      reduced 5-year mean total medical costs of -$3,907 (95% CI -$15,454 less to
      $7,640 more) compared with usual care patients. A sensitivity analysis found that
      these cost differences were largely explained by the patients with depression and
      the most severe medical comorbidity. CONCLUSIONS: The Pathways depression
      collaborative care program improved depression outcomes compared with usual care
      with no evidence of greater long-term costs and with trends for reduced costs
      among the more severely medically ill patients with diabetes.

PMID- 18332159
TI  - Cardiorespiratory fitness as a feature of metabolic syndrome in older men and
      women: the Dose-Responses to Exercise Training study (DR's EXTRA).
AB  - OBJECTIVE: We studied the associations of cardiorespiratory fitness with
      metabolic syndrome in older men and women, because such data are limited in
      representative population samples. RESEARCH DESIGN AND METHODS: We studied a
      population sample of 671 men and 676 women aged 57-79 years at baseline of a
      randomized controlled intervention study. We assessed maximal oxygen uptake
      (Vo(2max)) by respiratory gas analysis during a maximal bicycle exercise test.
      RESULTS: Vo(2max) had a strong, inverse, and graded association with the risk of
      having metabolic syndrome as defined by the National Cholesterol Education
      Program criteria. Men and women in the lowest third of Vo(2max) had 10.2- and
      10.8-fold higher risks and those in the middle third had 2.9- and 4.7-fold higher
      risks (P < 0.001 all) of metabolic syndrome than those with the highest Vo(2max)
      after multivariable adjustments. Factor analysis generated a principal factor
      that was strongly loaded by the main components of metabolic syndrome and
      Vo(2max) (-0.68 in men and -0.70 in women). CONCLUSIONS: Low cardiorespiratory
      fitness is associated with metabolic syndrome in older men and women. Our
      findings suggest that low cardiorespiratory fitness could be considered a feature
      of metabolic syndrome.

PMID- 18332160
TI  - Rarefaction of the peripheral nerve network in diabetic patients is associated
      with a pronounced reduction of terminal Schwann cells.
AB  - OBJECTIVE: Peripheral neuropathy is the most frequent neurological complication
      in diabetic patients. The diagnosis is established by both clinical neurological
      examination and demonstration of reduced epidermal nerve fibers in skin biopsies
      (1). Whereas the decrease of free nerve endings has been extensively studied in
      diabetic patients (2,3), no data are available on possible changes of terminal
      Schwann cells. Besides their role as scaffold for peripheral nerves, they also
      play an important role in supporting survival and function of peripheral nerves
      (4). RESEARCH DESIGN AND METHODS: We analyzed the subepidermal nerve plexus in
      dermal sheet preparations of deceased diabetic and nondiabetic patients by
      immunostaining for detection of the neural cell adhesion molecule and
      quantification of the subepidermal nerve plexus. RESULTS AND CONCLUSIONS: The
      subepidermal nerve plexus, comprising nerve fibers and ensheathing Schwann cells,
      was significantly reduced in diabetic patients. Whether the reduction in terminal
      Schwann cells is cause or consequence of the loss of peripheral nerve fibers
      remains to be investigated.

PMID- 18332161
TI  - Evaluation of a diabetes management system based on practice guidelines,
      integrated care, and continuous quality management in a Federal State of Germany:
      a population-based approach to health care research.
AB  - OBJECTIVE: The aim of this study was to evaluate the Saxon Diabetes Management
      Program (SDMP), which is based on integrated practice guidelines, shared care,
      and integrated quality management. The SDMP was implemented into diabetes
      contracts between health insurance providers, general practitioners (GPs), and
      diabetes specialized practitioners (DSPs) unified in the Saxon association of
      Statutory Health Insurance Physicians. RESEARCH DESIGN AND METHODS: The
      evaluation of the SDMP in Germany represents a real-world study by using clinical
      data collected from participating physicians. Between 2000 and 2002 all DSPs and
      about 75% of the GPs in Saxony participated. Finally, 291,771 patients were
      included in the SDMP. Cross-sectional data were evaluated at the beginning of
      2000 (group A1) and at the end of 2002 (group A2). A subcohort of 105,204
      patients was followed over a period of 3 years (group B). RESULTS: The statewide
      implementation of the SDMP resulted in a change in therapeutic practice and in
      better cooperation. The median A1C at the time of referral to DSPs decreased from
      8.5 to 7.5%, and so did the overall mean. At the end, 78 and 61% of group B
      achieved the targets for A1C and blood pressure, respectively, recommended by the
      guidelines compared with 69 and 50% at baseline. Patients with poorly controlled
      diabetes benefited the most. Preexisting regional differences were aligned.
      CONCLUSIONS: Integrated care disease management with practicable integrated
      quality management including collaboration between GPs and specialist services is
      a significant innovation in chronic care management and an efficient way to
      improve diabetes care continuously.

PMID- 18332162
TI  - Expression of erythropoietin and its receptor in the human retina: a comparative
      study of diabetic and nondiabetic subjects.
AB  - OBJECTIVE: The purpose of this study was to evaluate erythropoietin (Epo) and Epo
      receptor (EpoR) expression in the retina and in vitreous fluid from diabetic and
      nondiabetic donors. To gain insight into the mechanisms responsible for the
      regulation of Epo production in the retina, we also assessed retinal expression
      of hypoxia-inducible factors (HIF-1alpha and HIF-2alpha). RESEARCH DESIGN AND
      METHODS: Eighteen postmortem eyes from 9 diabetic patients without clinically
      detectable retinopathy were compared with 18 eyes from 9 nondiabetic donors. mRNA
      of Epo, HIF-1alpha, and HIF-2alpha (quantitative RT-PCR) were measured separately
      in neuroretina and retinal pigment epithelium (RPE). Epo and EpoR were assessed
      in the retina (immunofluorescence by confocal laser microscopy) and in the
      vitreous fluid (radioimmunoassay and enzyme-linked immunosorbent assay,
      respectively). RESULTS: Epo and EpoR mRNAs were significantly higher in the RPE
      than in the neuroretina. Higher expression of Epo was detected in the retinas
      (both in the RPE and in the neuroretina) from diabetic donors. By contrast, EpoR
      expression was similar in both groups. We did not find any difference in HIF
      1alpha and HIF-2alpha mRNA expression between diabetic and nondiabetic donors
      (both in RPE and neuroretina). Intravitreal Epo concentration was higher in
      diabetic donors than in nondiabetic control subjects. However, EpoR
      concentrations were similar in both groups. CONCLUSIONS: Epo overexpression is an
      early event in the retina of diabetic patients, and this is not associated with
      any change in EpoR. At this early stage, other factors apart from hypoxia seem to
      be more important in accounting for the Epo upregulation that exists in the
      diabetic retina.

PMID- 18332163
TI  - Hypoglycemia increases serum interleukin-6 levels in healthy men and women.
AB  - OBJECTIVE: Inflammation may have a major role in the pathogenesis and prognosis
      of critical illness. Hyperglycemia increases levels of the inflammatory cytokine
      interleukin-6 (IL-6) and is associated with increased risks of morbidity and
      mortality. Because hypoglycemia is also associated with adverse outcomes, we
      tested the hypothesis that hypoglycemia increases IL-6. RESEARCH DESIGN AND
      METHODS: Seventeen healthy men and women participated in hypoglycemic and
      euglycemic-hyperinsulinemic clamp studies (target blood glucose levels 2.7 and
      5.0 mmol/l, respectively), separated by 1-3 months. IL-6, ACTH, and cortisol were
      measured at baseline and at 45, 75, 105, and 135 min after initiation of the
      insulin infusion. RESULTS: IL-6, ACTH, and cortisol levels increased
      significantly (P < 0.0001) during hypoglycemia but not euglycemia. IL-6 increased
      from mean +/- SEM 1.0 +/- 0.2 pg/ml at baseline to 2.6 +/- 0.2 pg/ml after 135
      min of hypoglycemia, whereas IL-6 levels were unchanged during euglycemia.
      CONCLUSIONS: Hypoglycemia increases IL-6 levels in healthy individuals.

PMID- 18332164
TI  - Antibacterial efficacy of R-type pyocins towards Pseudomonas aeruginosa in a
      murine peritonitis model.
AB  - R-type pyocins are high-molecular-weight bacteriocins carried within the
      chromosomes of some bacterial species, such as Pseudomonas aeruginosa, and almost
      certainly evolved from lysogenic bacteriophages of the Myoviridae family. They
      contain no head structures and no DNA and are used as defense systems, usually
      against other strains of the same bacterial species. They bind with their tail
      fibers to targeted bacterial surface molecules and then kill by inserting a core
      or needle that dissipates the bacterial membrane potential. Their mechanism of
      action, high bactericidal potency (one pyocin particle can kill one bacterium),
      and focused spectrum suggest that R-type pyocins could be developed as
      antibacterial agents. In a lethal mouse peritonitis model, submicrogram
      quantities of pyocin prevent death from 90% lethal dose inocula of a pyocin
      sensitive, clinical isolate of P. aeruginosa. We show here the dose response
      curves, treatment windows, or periods of response after infection and the several
      log-unit acute reduction of bacterial load in blood and spleen samples,
      suggesting that R-type pyocins have several characteristics that one would expect
      from an effective therapeutic.

PMID- 18332165
TI  - The antimicrobial peptide NK-2, the core region of mammalian NK-lysin, kills
      intraerythrocytic Plasmodium falciparum.
AB  - In a time of dramatically increasing resistance of microbes to all kinds of
      antibiotics, natural antimicrobial peptides and synthetic analogs thereof have
      emerged as compounds with potentially significant therapeutical applications
      against human pathogens. Only very few of these peptide antibiotics have been
      tested against protozoan pathogens that are a major cause of morbidity and
      mortality in large parts of the world. Here, we studied the effect of NK-2, a
      peptide representing the cationic core region of the lymphocytic effector protein
      NK-lysin, on the malaria parasite Plasmodium falciparum. Whereas noninfected red
      blood cells were hardly affected, human erythrocytes infected with the parasite
      were rapidly permeabilized by NK-2 in the micromolar range. Loss of plasma
      membrane asymmetry and concomitant exposure of phosphatidylserine upon infection
      appears to be the molecular basis for the observed target preference of NK-2, as
      can be demonstrated by annexin V binding. The peptide also affects the viability
      of the intracellular parasite, as evidenced by the drop in DNA content of
      cultured parasites. Accumulated evidence derived from permeabilization assays
      using parasites and liposomes as targets and from fluorescence microscopy of
      infected erythrocytes treated with fluorescently labeled NK-2 indicates that the
      positively charged peptide electrostatically interacts with the altered and
      negatively charged plasma membrane of the infected host cell and traverses this
      membrane as well as the parasitophorous vacuole membrane to reach its final
      target, the intracellular parasite. The apparent affinity for foreign membranes
      that resulted in the death of a eukaryotic parasite residing in human host cells
      makes NK-2 a promising template for novel anti-infectives.

PMID- 18332166
TI  - Mitochondrial DNA content, an inaccurate biomarker of mitochondrial alteration in
      human immunodeficiency virus-related lipodystrophy.
AB  - Lipoatrophy is a prevalent side effect of antiretroviral treatment of human
      immunodeficiency virus (HIV) infection. Its mechanisms are still disputed but
      include mitochondrial toxicity and, in particular, mitochondrial DNA (mtDNA)
      depletion induced by nucleoside reverse transcriptase inhibitors. To obtain an
      integrated evaluation of the mitochondrial alteration in lipoatrophy, we
      investigated the DNA, RNA, and protein levels in 15 samples of abdominal
      subcutaneous adipose tissue from HIV-infected patients with peripheral
      lipoatrophy and compared the results with those for 15 samples from age- and body
      mass index-matched controls. The DNA and RNA analyses used PCR-based techniques,
      while proteins were quantified with enzyme-linked immunosorbent assay and
      measurement of activities with spectrophotometric assays. Depletion of mtDNA and
      mtDNA-encoded MT-CO2 mRNA was present, but normal levels of mtDNA-dependent
      activity (cytochrome c oxidase) and protein (MT-CO2p) showed that it was
      compensated for. An increase in nuclear-DNA-dependent mitochondrial activities
      (citrate synthase and malate dehydrogenase) and protein (COX4I1p), as well as
      transcriptional up-regulation of nuclear-DNA-encoded mitochondrial genes (COX4I1
      and UCP2), demonstrated increased mitochondrial biogenesis. However, the
      expression of the known transcription factors of mitochondrial biogenesis (TFAM,
      NRF1, GABPA, PPARGC1A, PPARGC1B, and PPRC1) was normal or decreased. Increased
      amounts of activated caspase 3 and of DDIT3 mRNA showed the induction of
      apoptosis and oxidative stress, respectively. The mtDNA content did not correlate
      with any other mitochondrial parameter. In conclusion, mtDNA content does not
      appear to be an accurate biomarker of mitochondrial alteration in lipoatrophic
      adipose tissue. The preservation of mtDNA-dependent mitochondrial functions
      occurred despite severe mtDNA depletion. The presence of significant oxidative
      stress and apoptosis did not correlate with the mtDNA content.

PMID- 18332167
TI  - Synergy of a hepatitis C virus (HCV) NS4A antagonist in combination with HCV
      protease and polymerase inhibitors.
AB  - Rapid emergence of resistance to monotherapy with virus-specific inhibitors
      necessitates combination therapy. ACH-806 is a hepatitis C virus NS4A inhibitor
      with a novel mechanism of action and resistance pathway. This compound was
      synergistic with NS3 protease inhibitors and NS5B nucleoside and nonnucleoside
      polymerase inhibitors.

PMID- 18332168
TI  - Secretion of E,E-farnesol and biofilm formation in eight different Candida
      species.
AB  - Production of E,E-farnesol (FOH) and biofilm formation were studied under various
      conditions in 56 strains of eight Candida spp. FOH production differed
      significantly not only between Candida spp. but within Candida albicans strains
      as well. FOH concentrations and biofilm formation were the highest for C.
      albicans.

PMID- 18332169
TI  - Efficacy of benzoxazinorifamycins in a mouse model of Chlamydia pneumoniae lung
      infection.
AB  - The efficacy of rifalazil and other benzoxazinorifamycins was tested in a mouse
      model of lung infection against Chlamydia pneumoniae. Rifalazil and six related
      new chemical entities all showed efficacy after one dose per day for 3 days at
      either 3 or 1 mg/kg of body weight.

PMID- 18332170
TI  - Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered
      once daily for 7 days compared to penicillin V potassium administered four times
      daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus
      pyogenes in children.
AB  - An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time
      above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus
      pyogenes reported in the literature) was shown to be achievable in a phase 1
      study of 23 children with a once-daily (QD) modified-release, multiparticulate
      formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with
      the QD amoxicillin sprinkle formulation was comparable to that achieved with a
      four-times-daily (QID) penicillin VK suspension. An investigator-blinded,
      randomized, parallel-group, multicenter study involving 579 children 6 months to
      12 years old with acute streptococcal tonsillopharyngitis was then undertaken.
      Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle
      (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7
      days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the
      maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological
      eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle
      and 68.0% (132/194) for penicillin VK (95% confidence interval, -12.0% to 6.6%).
      Thus, neither antibiotic regimen met the minimum criterion of > or =85%
      eradication ordinarily required by the U.S. FDA for first-line treatment of
      tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across
      demographic characteristics and current infection characteristics and by
      age/weight categories were consistent with the primary-efficacy result. The
      clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1%
      (216/251) and 91.9% (204/222), respectively (95% confidence interval, -11.6% to 
      0.4%). The results of a post hoc PD analysis suggested that a requirement for 60%
      daily T >MIC(90) more accurately predicted the observed high failure rates for
      bacteriologic eradication with the amoxicillin sprinkle and penicillin VK
      suspension studied. Based on the association between longer treatment courses and
      maximal bacterial eradication rates reported in the literature, an alternative
      composite PK/PD target taking into consideration the duration of therapy, or
      total T >MIC, was considered and provides an alternative explanation for the
      observed failure rate of amoxicillin sprinkle.

PMID- 18332171
TI  - Mouse beta-defensin-14, an antimicrobial ortholog of human beta-defensin-3.
AB  - Searching the database for mouse homologs of the antimicrobial peptide human beta
      defensin-3 (hBD-3) revealed highest identity (69%) to mouse beta-defensin-14 (mBD
      14). Recombinant mBD-14 exhibited broad-spectrum, nanomolar microbicidal
      activity. Treatment of keratinocytes with gamma interferon or transforming growth
      factor alpha increased mBD-14 gene expression. These data suggest that mBD-14 is
      the functional ortholog of hBD-3.

PMID- 18332172
TI  - Activities of daptomycin and comparative antimicrobials, singly and in
      combination, against extracellular and intracellular Staphylococcus aureus and
      its stable small-colony variant in human monocyte-derived macrophages and in
      broth.
AB  - We investigated the antistaphylococcal activities of daptomycin, gentamicin, and
      rifampin against two Staphylococcus aureus strains and their stable small-colony
      variants, singly and in combination, in human monocyte-derived macrophages and in
      broth. Intracellularly, the three-drug combination and two-drug combinations with
      rifampin were most effective. Extracellularly, daptomycin, daptomycin plus
      gentamicin, gentamicin plus rifampin, and the three-drug combination had similar
      activities.

PMID- 18332173
TI  - Buthionine sulfoximine has anti-Trypanosoma cruzi activity in a murine model of
      acute Chagas' disease and enhances the efficacy of nifurtimox.
AB  - L-buthionine (S,R)-sulfoximine (BSO) at a dose of 220 mg/kg of body weight/day
      showed an anti-Trypanosoma cruzi effect in infected mice, increasing their
      survival rate and decreasing the parasitemias and parasite burden in the hearts.
      Treatment with BSO plus nifurtimox caused an increase in the survival rate in
      comparison to the rates with treatment with each drug alone.

PMID- 18332174
TI  - Inhibitory effect of PRO 2000, a candidate microbicide, on dendritic cell
      mediated human immunodeficiency virus transfer.
AB  - Without an effective vaccine against human immunodeficiency virus (HIV)
      infection, topical microbicide development has become a priority. The sulfonated
      polyanion PRO 2000, a candidate topical microbicide now in phase II/III clinical
      trials, blocks HIV infection of cervical tissue in vitro. Dendritic cells (DC)
      are among the first cell types to contact HIV in the genital tract and facilitate
      the spread of the virus. Thus, interfering with virus-DC interactions is a
      desirable characteristic of topical microbicides as long as that does not
      interfere with the normal function of DC. PRO 2000 present during capture of the
      replication-defective HIV(JRFL) reporter virus or replication-competent HIV(BaL)
      by monocyte-derived DC (MDDC) inhibited subsequent HIV transfer to target cells.
      Continuous exposure to PRO 2000 during MDDC-target cell coculture effectively
      inhibited HIV infection of target cells. PRO 2000 inhibited HIV capture by MDDC.
      In addition, the compound blocked R5 and X4 HIV envelope-mediated cell-cell
      fusion. Interestingly, simultaneous exposure to PRO 2000 and lipopolysaccharide
      attenuated the cytokine production in response to stimulation, suggesting that
      the compound altered DC function. While efficient blocking of MDDC-mediated virus
      transfer and infection in the highly permissive MDDC-T-cell environment
      reinforces the potential value of PRO 2000 as a topical microbicide against HIV,
      the impact of PRO 2000 on immune cell functions warrants careful evaluation.

PMID- 18332175
TI  - Efficacies of ceftobiprole medocaril and comparators in a rabbit model of
      osteomyelitis due to methicillin-resistant Staphylococcus aureus.
AB  - The pharmacokinetics and distribution into bone tissue of ceftobiprole in
      uninfected New Zealand White rabbits were determined after subcutaneous
      administration of the prodrug ceftobiprole medocaril. Serum exposure (maximum
      concentration of the drug in serum, trough concentration, area under the
      concentration-time curve) to ceftobiprole at 20 and 80 mg/kg was dose
      proportional, and there was no accumulation of ceftobiprole following repeated
      (every 6 h [q6h]) injections of the antibiotic. Ceftobiprole titers in the tibial
      matrix and marrow were 3.2 +/- 1.3 microg/g and 11.2 +/- 6.5 microg/g,
      respectively, in uninfected animals treated with 20 mg/kg of the antibiotic and
      13.4 +/- 7.3 microg/g and 66.3 +/- 43.2 microg/g, respectively, in uninfected
      animals treated with 80 mg/kg of the antibiotic. No differences in ceftobiprole
      titers were observed between right and left tibiae for either bone matrix or
      marrow. The efficacies of 4 weeks of treatment with ceftobiprole (40 mg/kg
      administered subcutaneously [s.c.] q6h), vancomycin (30 mg/kg administered s.c.
      q12h), or linezolid (60 mg/kg administered orally q8h) were compared, using a
      rabbit model of methicillin-resistant Staphylococcus aureus tibial osteomyelitis.
      After treatment with ceftobiprole, the bacterial titers in all infected left
      tibiae from evaluable rabbits were below the level of detection, whereas only 73%
      of infected left tibiae from vancomycin- or linezolid-treated animals had
      bacterial titers below the level of detection; the mean titers of ceftobiprole
      were 3 to 5 times higher in infected left tibiae than in uninfected right tibiae.
      These results indicate that ceftobiprole provided effective parenteral treatment
      of osteomyelitis in this rabbit model.

PMID- 18332176
TI  - Emergence of Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli
      Isolates possessing the plasmid-mediated carbapenem-hydrolyzing beta-lactamase
      KPC-2 in intensive care units of a Chinese hospital.
AB  - Twenty-one Serratia marcescens, ten Klebsiella pneumoniae, and one Escherichia
      coli isolate with carbapenem resistance or reduced carbapenem susceptibility were
      recovered from intensive care units (ICUs) in our hospital. Enterobacterial
      repetitive intergenic consensus-PCR and pulsed-field gel electrophoresis
      demonstrated that all the S. marcescens isolates belonged to a clonal strain and
      the 10 K. pneumoniae isolates were indistinguishable or closely related to each
      other. The MICs of imipenem, meropenem, and ertapenem for all isolates were 2 to
      8 microg/ml, except for K. pneumoniae K10 (MICs of 128, 256, and >256 microg/ml).
      Isoelectric focusing, PCRs, and DNA sequencing indicated that all S. marcescens
      isolates produced KPC-2 and a beta-lactamase with a pI of 6.5. All K. pneumoniae
      isolates produced TEM-1, KPC-2, CTX-M-14, and a beta-lactamase with a pI of 7.3.
      The E. coli E1 isolate produced KPC-2, CTX-M-15, and a beta-lactamase with a pI
      of 7.3. Conjugation studies with E. coli (EC600) resulted in the transfer of
      reduced carbapenem susceptibility compared to that of the original isolates, and
      only the bla(KPC-2) gene was detected in E. coli transconjugants. Plasmid
      restriction analysis showed identical restriction patterns among all E. coli
      transconjugants. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and
      ompK35/36 gene sequence analysis of outer membrane proteins revealed that K.
      pneumoniae K10 failed to express OmpK36, because of insertional inactivation by
      an insertion sequence ISEcp1. All these results indicate that KPC-2-producing S.
      marcescens, K. pneumoniae, and E. coli isolates emerged in ICUs in our hospital.
      KPC-2 combined with porin deficiency results in high-level carbapenem resistance
      in K. pneumoniae. The same bla(KPC-2)-encoding plasmid was spread among the three
      different genera.

PMID- 18332177
TI  - "Keepin' my mind right": identity maintenance and religious social support in the
      prison context.
AB  - It is not uncommon for inmates to experience religious conversions in prison.
      These conversions allow inmates to portray themselves in a prosocial light and
      help them to establish a sense of control in their current lives, regardless of
      their past. Despite the value of these conversions, maintaining a new outlook of
      one's self is remarkably difficult. Using semistructured interviews with 63
      inmates who had undergone a religious conversion, the authors examine the process
      that they engaged in to keep these new senses of self. The narratives suggest
      that they relied on various social support mechanisms to keep themselves focused
      and inspired. Specifically, they stressed the importance of connecting with
      positive others in formal and informal settings, sharing their stories with those
      in need, and reflecting on their daily choices. It is through these strategies
      that inmates keep the inspiration and focus to "keep their minds right."

PMID- 18332178
TI  - A gammaherpesvirus-secreted activator of Vbeta4+ CD8+ T cells regulates chronic
      infection and immunopathology.
AB  - Little is known about herpesvirus modulation of T cell activation in latently
      infected individuals or the implications of such for chronic immune disorders.
      Murine gammaherpesvirus 68 (MHV68) elicits persistent activation of CD8(+) T
      cells bearing a Vbeta4(+) T cell receptor (TCR) by a completely unknown
      mechanism. We show that a novel MHV68 protein encoded by the M1 gene is
      responsible for Vbeta4(+) CD8(+) T cell stimulation in a manner reminiscent of a
      viral superantigen. During infection, M1 expression induces a Vbeta4(+) effector
      T cell response that resists functional exhaustion and appears to suppress virus
      reactivation from peritoneal cells by means of long-term interferon-gamma
      (IFNgamma) production. Mice lacking an IFNgamma receptor (IFNgammaR(-/-)) fail to
      control MHV68 replication, and Vbeta4(+) and CD8(+) T cell activation by M1
      instead contributes to severe inflammation and multiorgan fibrotic disease. Thus,
      M1 manipulates the host CD8(+) T cell response in a manner that facilitates
      latent infection in an immunocompetent setting, but promotes disease during a
      dysregulated immune response. Identification of a viral pathogenecity determinant
      with superantigen-like activity for CD8(+) T cells broadens the known repertoire
      of viral immunomodulatory molecules, and its function illustrates the delicate
      balance achieved between persistent viruses and the host immune response.

PMID- 18332179
TI  - Age-associated decline in T cell repertoire diversity leads to holes in the
      repertoire and impaired immunity to influenza virus.
AB  - A diverse T cell repertoire is essential for a vigorous immune response to new
      infections, and decreasing repertoire diversity has been implicated in the age
      associated decline in CD8 T cell immunity. In this study, using the well
      characterized mouse influenza virus model, we show that although comparable
      numbers of CD8 T cells are elicited in the lung and lung airways of young and
      aged mice after de novo infection, a majority of aged mice exhibit profound
      shifts in epitope immunodominance and restricted diversity in the TCR repertoire
      of responding cells. A preferential decline in reactivity to viral epitopes with
      a low naive precursor frequency was observed, in some cases leading to "holes" in
      the T cell repertoire. These effects were also seen in young thymectomized mice,
      consistent with the role of the thymus in maintaining naive repertoire diversity.
      Furthermore, a decline in repertoire diversity generally correlated with impaired
      responses to heterosubtypic challenge. This study formally demonstrates in a
      mouse infection model that naturally occurring contraction of the naive T cell
      repertoire can result in impaired CD8 T cell responses to known immunodominant
      epitopes and decline in heterosubtypic immunity. These observations have
      important implications for the design of vaccine strategies for the elderly.

PMID- 18332180
TI  - IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances
      clearance of persistent virus infection.
AB  - Therapeutic vaccination is a potentially powerful strategy to establish immune
      control and eradicate persistent viral infections. Large and multifunctional
      antiviral T cell responses are associated with control of viral persistence;
      however, for reasons that were mostly unclear, current therapeutic vaccination
      approaches to restore T cell immunity and control viral infection have been
      ineffective. Herein, we confirmed that neutralization of the immunosuppressive
      factor interleukin (IL)-10 stimulated T cell responses and improved control of
      established persistent lymphocytic choriomeningitis virus (LCMV) infection.
      Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic
      DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell
      responses and enhancing clearance of persistent LCMV replication. We therefore
      propose that a reason that current therapeutic vaccination strategies fail to
      resurrect/sustain T cell responses is because they do not alleviate the
      immunosuppressive environment. Consequently, blocking key suppressive factors
      could render ineffective vaccines more efficient at improving T cell immunity,
      and thereby allow immune-mediated control of persistent viral infection.

PMID- 18332181
TI  - Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals
      during chronic infection.
AB  - Therapeutic vaccination is a potentially promising strategy to enhance T cell
      immunity and viral control in chronically infected individuals. However,
      therapeutic vaccination approaches have fallen short of expectations, and
      effective boosting of antiviral T cell responses has not always been observed.
      One of the principal reasons for the limited success of therapeutic vaccination
      is that virus-specific T cells become functionally exhausted during chronic
      infections. We now provide a novel strategy for enhancing the efficacy of
      therapeutic vaccines. In this study, we show that blocking programmed death (PD)
      1/PD-L1 inhibitory signals on exhausted CD8(+) T cells, in combination with
      therapeutic vaccination, synergistically enhances functional CD8(+) T cell
      responses and improves viral control in mice chronically infected with
      lymphocytic choriomeningitis virus. This combinatorial therapeutic vaccination
      was effective even in the absence of CD4(+) T cell help. Thus, our study defines
      a potent new approach to augment the efficacy of therapeutic vaccination by
      blocking negative signals. Such an approach may have broad applications in
      developing treatment strategies for chronic infections in general, and perhaps
      also for tumors.

PMID- 18332182
TI  - CD94-NKG2A recognition of human leukocyte antigen (HLA)-E bound to an HLA class I
      leader sequence.
AB  - The recognition of human leukocyte antigen (HLA)-E by the heterodimeric CD94-NKG2
      natural killer (NK) receptor family is a central innate mechanism by which NK
      cells monitor the expression of other HLA molecules, yet the structural basis of
      this highly specific interaction is unclear. Here, we describe the crystal
      structure of CD94-NKG2A in complex with HLA-E bound to a peptide derived from the
      leader sequence of HLA-G. The CD94 subunit dominated the interaction with HLA-E,
      whereas the NKG2A subunit was more peripheral to the interface. Moreover, the
      invariant CD94 subunit dominated the peptide-mediated contacts, albeit with poor
      surface and chemical complementarity. This unusual binding mode was consistent
      with mutagenesis data at the CD94-NKG2A-HLA-E interface. There were few
      conformational changes in either CD94-NKG2A or HLA-E upon ligation, and such a
      "lock and key" interaction is typical of innate receptor-ligand interactions.
      Nevertheless, the structure also provided insight into how this interaction can
      be modulated by subtle changes in the peptide ligand or by the pairing of CD94
      with other members of the NKG2 family. Differences in the docking strategies used
      by the NKG2D and CD94-NKG2A receptors provided a basis for understanding the
      promiscuous nature of ligand recognition by NKG2D compared with the fidelity of
      the CD94-NKG2 receptors.

PMID- 18332183
TI  - Fixing DNA breaks during class switch recombination.
AB  - Immunoglobulin (Ig) class switch recombination (CSR) involves the breakage and
      subsequent repair of two DNA sequences, known as switch (S) regions, which flank
      IgH constant region exons. The resolution of CSR-associated breaks is thought to
      require the nonhomologous end-joining (NHEJ) DNA repair pathway, but the role of
      the NHEJ factor DNA-dependent protein kinase catalytic subunit (DNA-PKcs) in this
      process has been unclear. A new study, in which broken IgH-containing chromosomes
      in switching B cells were visualized directly, clearly demonstrated that DNA-PKcs
      and, unexpectedly, the nuclease Artemis are involved in the resolution of switch
      breaks.

PMID- 18332184
TI  - Going outdoors daily predicts long-term functional and health benefits among
      ambulatory older people.
AB  - OBJECTIVE: This article examines the association between frequency of going out
      of the house and health and functional status among older people. METHOD: A
      randomly chosen cohort of ambulatory participants born in 1920 or 1921 from the
      Jerusalem Longitudinal Study underwent assessments for health, functional, and
      psychosocial variables at ages 70 and 77. Twelve-year mortality data were
      collected. RESULTS: Women went out daily less than did men. Participants going
      out daily at age 70 reported significantly fewer new complaints at age 77 of
      musculoskeletal pain, sleep problems, urinary incontinence, and decline in
      activities of daily living (ADLs). Logistic regression analysis indicated that
      not going out daily at age 70 was predictive of subsequent dependence in ADL,
      poor self-rated health, and urinary incontinence at age 77. DISCUSSION: Going out
      daily is beneficial among independent older people, correlating with reduced
      functional decline and improved health measures.

PMID- 18332185
TI  - Education and psychological distress among older Chinese.
AB  - OBJECTIVE: The goal of this research is to see if more highly educated older
      Chinese have lower levels of distress than do their poorly educated counterparts
      and whether engaging in cognitively stimulating activities such as reading and
      playing mahjong explains the association. METHOD: Using the Chinese Healthy
      Longevity Survey, the authors find a significant negative association between
      education and psychological distress. Much of the association is mediated by
      activities, but not all in the ways expected. Reading, playing mahjong, and
      watching television all negatively correlate with distress. DISCUSSION: Better
      educated older Chinese have lower levels of distress than do their less-well
      educated counterparts in part because they engage in cognitively stimulating
      activities, have better economic circumstances, and engage in more physical
      activity.

PMID- 18332186
TI  - Effects of own and spousal disability on loneliness among older adults.
AB  - OBJECTIVES: This study examines the effects of own and spousal disability on
      social and emotional loneliness among married adults aged 65 and older. METHOD:
      Data from 710 men and 379 women of a Dutch community sample were analyzed with
      linear regression analyses. RESULTS: For men, only their wives' disability was
      related to higher levels of social loneliness, whereas for women mainly their own
      disability was related to higher levels of social loneliness. Own disability and
      spousal disability were related to higher levels of emotional loneliness among
      both men and women. Effects of disability remained unaffected after controlling
      for characteristics of the social network and the marital relationship.
      DISCUSSION: Findings underscore the importance of considering effects of both
      spouses' health on measures of individual well-being. Also, the traditional
      division of social roles makes older married men relatively vulnerable to social
      loneliness when their wives suffer from disability.

PMID- 18332187
TI  - Racial and ethnic variations in caregiver service use.
AB  - OBJECTIVE: This article examines whether race and ethnicity contribute to the
      differential use of caregiver support services, when controlling for caregiver
      and care recipient characteristics, as represented by predisposing, enabling, and
      need factors included in the Behavioral Model of Health Services Use. METHODS:
      The study includes 1,508 individuals who provide care to an ill or disabled adult
      aged 50 or older, identified through a random digit dial telephone survey of
      California households. Logistic regression analysis is utilized to examine
      factors that predict use of caregiver support services. RESULTS: Race and
      ethnicity do not contribute significantly to caregiver service utilization, when
      controlling for relevant covarying factors such as age, education, emotional
      support, family contribution, care recipient service use, and care recipient
      impairment. A significant interaction exists between ethnicity and family
      closeness, with reduced rates of service use among Asian and Pacific Island
      caregivers whose families are brought closer by the caregiving experience.
      DISCUSSION: These findings suggest that racial and ethnic disparities in
      caregiver service use found at the bivariate level are attributable to covarying
      predisposing, enabling, and need factors. Further research and theoretical
      development are suggested to clarify the impact of sociocultural factors on
      caregiver service use.

PMID- 18332188
TI  - Life course socioeconomic disadvantage and cognitive function among the elderly
      population of seven capitals in Latin America and the Caribbean.
AB  - OBJECTIVE: To examine the influence of life course socioeconomic disadvantages
      (SED) on cognitive function in later life. METHOD: Data originate from a survey
      of people 60 and older living in seven Latin American and Caribbean cities.
      Cognitive function was measured with a modified Mini-Mental State Examination and
      the Pfeffer Scale of Functional Capacity. Homogeneity tests were used to pool
      data. Associations between cognitive function and SED were evaluated, fitting
      logistic regressions. RESULTS: Cognitive impairment (CI) prevalence ranged from
      0.3% to 6.5% in men and 1.2% to 10.1% in women. Childhood rural living, poor
      childhood health, illiteracy, housewife or farmer occupation, and insufficient
      income were associated with CI in all seven cities. The odds of CI increase with
      cumulative exposure to disadvantages along life course. CONCLUSIONS: Life course
      SED is related to cognitive function later in life. Difficulty in properly
      distinguishing cognitive function from test performance remains an issue.

PMID- 18332189
TI  - Age differences in memory for arousing and nonarousing emotional words.
AB  - Older adults sometimes demonstrate a mnemonic "positivity effect," remembering
      more positive than negative information. The present study examined whether this
      effect would occur for arousing words (elation vs slaughter) or for nonarousing
      ones (serenity vs sorrow). The results revealed no positivity effect for arousing
      words: Young and older adults remembered negative and positive arousing words
      equally well and more often than neutral words. However, a positivity effect
      emerged for nonarousing words. Young adults remembered negative nonarousing words
      better than positive nonarousing items. Older adults remembered positive
      nonarousing words better than negative nonarousing words and showed no mnemonic
      benefit for negative nonarousing words as compared with neutral words. These
      findings suggest that aging preserves responses to arousing information while
      altering the processing of nonarousing information.

PMID- 18332190
TI  - Physical activity in prefrail older adults: confidence and satisfaction related
      to physical function.
AB  - We examined the hypothesis that physical activity will have favorable effects on
      measures of self-efficacy for a 400-m walk and satisfaction with physical
      functioning in older adults 70+ years of age who have deficits in mobility. We
      randomized a total of 412 adults aged 70-89 years at elevated risk for mobility
      disability to either a physical activity or a successful aging educational
      control intervention for 12 months. Participants in the physical activity
      intervention had more favorable changes in both outcomes as a result of treatment
      than those in the successful aging intervention. Gender, age, and scores on a
      short physical performance battery did not moderate these effects. Physical
      activity is an effective means of intervening on self-efficacy and satisfaction
      with physical function in older adults with impaired lower extremity functioning.
      This is an important finding in light of the importance of these process
      variables in behavior change and quality of life.

PMID- 18332191
TI  - Within-group differences in depression among older Hispanics living in the United
      States.
AB  - Using the Health and Retirement Study, we examine the prevalence of depression in
      different groups of Hispanic older adults. Respondents (n = 759) were aged 59 and
      older and identified themselves as Mexican American (56%), Cuban American (13%),
      Puerto Rican (8%), other (8%), or not specified (15%). We used a modified version
      of the Center for Epidemiologic Studies-Depression scale and the Composite
      International Diagnostic Interview to assess depressive symptoms and the presence
      of major depression. Relative to Puerto Ricans, each Hispanic group had
      significantly lower levels of depressive symptoms, except for Cuban Americans;
      and each Hispanic group had lower prevalence rates for major depression, except
      for other Hispanics, even after we adjusted for sociodemographic, cultural
      factors, socioeconomic, functional limitations, and chronic health conditions.

PMID- 18332193
TI  - When parents matter to their adult children: filial reliance associated with
      parents' depressive symptoms.
AB  - A neglected topic in aging depression research is the potential role of the
      parent-adult child relationship. In this study we examined whether adult
      children's reports of having relied upon parents for instrumental and expressive
      support are associated with parents' depressive symptoms. The sample included 304
      parents (aged 50-72 years), matched to a randomly selected adult offspring, from
      the University of Southern California Longitudinal Study of Generations. We
      measured parents' depressive symptoms by using the Center for Epidemiologic
      Studies Depression Scale at baseline and 3 and 6 years later. The final
      longitudinal analysis showed that, when we adjusted for relevant variables
      including age, gender, income, self-rated health, and child's depressive
      symptoms, the adult child's reliance on instrumental support was associated with
      fewer parental depressive symptoms (p =.036). Expressive support did not show the
      same pattern. Thus, adult children's reliance on instrumental support might
      contribute to their parents' mental health.

PMID- 18332195
TI  - Spousal social activity trajectories in the Australian longitudinal study of
      ageing in the context of cognitive, physical, and affective resources.
AB  - We examined the dyadic interdependence of spousal social activity trajectories
      over 11 years by using longitudinal data on 565 couples from the Australian
      Longitudinal Study of Ageing (M age = 76 years at Time 1). Social activity
      trajectories were interrelated in elderly couples, and they depended not only on
      individual but also on spousal cognitive, physical, and affective resources at
      baseline. Most associations examined were similar in husbands and wives. However,
      wives performed more social activities and displayed different depression-social
      activity associations than did husbands. We found stronger within-couple
      associations in the domain of social activities than for cognition. Our findings
      illustrate the important role of social relationships for late-life development
      and suggest that the mechanisms involved in dyadic interdependencies may be
      domain and gender specific.

PMID- 18332196
TI  - Longitudinal predictors of driving cessation among older adults from the ACTIVE
      clinical trial.
AB  - We examined the physical, visual, health, and cognitive abilities of 1,656 older
      adults as prospective predictors of self-reported driving cessation over a 5-year
      period. We examined the time to driving cessation across 5 years after we
      controlled for days driven per week at baseline and any cognitive intervention
      participation. Older age, congestive heart failure, and poorer physical
      performance (according to the Turn 360 Test) were statistically significant risk
      factors for driving cessation. Slower speed of processing (according to the Digit
      Symbol Substitution and Useful Field of View tests) was a significant risk factor
      even after we took baseline driving, age, health, vision, and physical
      performance into consideration. Implications are that assessments of cognitive
      speed of processing can provide valuable information about the subsequent risk of
      driving cessation.

PMID- 18332197
TI  - Employment hardship among older workers: does residential and gender inequality
      extend into older age?
AB  - OBJECTIVES: The realities of a rapidly aging society make the employment
      circumstances of older workers an increasingly important social issue. We examine
      the prevalence and correlates of underemployment among older Americans, with a
      special focus on residence and gender, to provide an assessment of the labor
      market challenges facing older workers. METHODS: We analyzed data from the March
      Current Population Surveys for the years 2003, 2004, and 2005. We used
      descriptive statistics to explore the prevalence of underemployment among older
      workers and developed multivariate models to assess the impact of age, residence,
      and gender on the likelihood of underemployment, net of other predictors.
      RESULTS: We found clear disadvantages for older workers relative to their middle
      aged counterparts, and particular disadvantages for older rural residents and
      women. Multivariate models showed that the disadvantages of older age held net of
      other predictors. The results also indicated that much of the disadvantage faced
      by older rural workers and women was explained by factors other than age,
      particularly education. DISCUSSION: In an aging society, underemployment among
      older workers comes at an increasing social cost. Policies aimed at supporting
      older workers and alleviating employment hardship among them are increasingly in
      the public interest.

PMID- 18332198
TI  - Early life influences on cognitive impairment among oldest old Chinese.
AB  - OBJECTIVES: This article examines the effects of early life socioeconomic
      conditions on the risk of cognitive impairment among oldest old persons in China.
      We also examine whether adult socioeconomic status mediates the association
      between early life socioeconomic status and cognitive impairment in old age.
      METHODS: Data derived from two waves (1998-2000) of the Chinese Longitudinal
      Healthy Longevity Survey. We estimated logistic and multinomial regression models
      of cognitive impairment for a nationwide sample of people aged 80 to 105 (N =
      8,444). RESULTS: Among both men and women, urban residence in early life as well
      as education was associated with lower odds of cognitive impairment at baseline.
      We found modest support for a protective effect of advantaged childhood
      background on the odds of cognitive impairment onset during the 2-year follow-up,
      especially among women. DISCUSSION: Our findings suggest that socioeconomic
      environment throughout the life course, early life in particular, can influence
      the risk of cognitive impairment in old age. Not only can public policy that
      targets illiteracy, hunger, and poverty improve the lives of tens of thousands of
      children, but ultimately such investments will pay significant dividends many
      decades later in enhancing the cognitive well-being of older persons.

PMID- 18332199
TI  - Gerontology's greatest hits.

PMID- 18332200
TI  - Racial and ethnic disparities in mobility device use in late life.
AB  - OBJECTIVE: Although racial and ethnic disparities in disability are well
      established and technology is increasingly used to bridge gaps between functional
      deficits and environmental demands, little research has focused on racial and
      ethnic disparities in device use. This study investigated whether use of mobility
      devices differs by race and ethnicity and explored several reasons for this
      difference. METHODS: The sample included community-dwelling adults aged 65 and
      older from the 2002 and 2004 waves of the Health and Retirement Study. We used
      predisposing, need, and enabling factors to predict mobility device use alone and
      combined with personal care. RESULT: Blacks had the highest rates of using
      mobility devices, followed by Hispanics and then Whites. Need and enabling
      factors explained differences between Blacks and Whites in wheelchair use but not
      cane use or use of devices without personal care. Other predisposing factors
      explained most differences between Hispanics and Whites. DISCUSSION: Because
      minorities appear to be using mobility devices in proportion to underlying need,
      increasing device use by minorities may not reduce disparities in mobility
      disability. Efforts to address racial/ethnic disparities in mobility disability
      in late life, therefore, may need to focus on differences in underlying
      functional decline rather than the accommodation of it.

PMID- 18332201
TI  - Sex and gender in older adults' experience of Parkinson's disease.
AB  - OBJECTIVES: This article reports on the gendered experience of Parkinson's
      disease (PD). Data derived from 15 months of ethnographic study among community
      dwelling older adults living with PD in eastern Iowa. METHODS: The study utilized
      several methods: participant observation at PD support group meetings, illness
      narrative interviews with PD sufferers, and a questionnaire. RESULTS: A total of
      171 PD sufferers (106 men, 65 women) enrolled in the study. Illness narratives
      revealed gender differences in the impact of specific symptoms on daily life:
      Women's narratives emphasized the impact of the on/off effect and "thinking
      problems," whereas men's narratives emphasized the consequences of their physical
      appearance. In comparison, quantitative data found little sex difference in
      symptomatology. DISCUSSION: The comparison of qualitatively and quantitatively
      derived data reveals the importance of attending to both sex and gender.
      Qualitative data demonstrate how the meaning of PD symptoms is gendered and
      illustrate an example of how gender and sex research differ. All narratives
      reflect the importance of role continuity, but men's put at the forefront
      appearance and social isolation whereas women's underscore their relational
      aspects of domestic activities. These data imply that providers must look beyond
      symptomatology to the gendered saliency of particular somatic phenomena.

PMID- 18332202
TI  - The effect of widowhood on intergenerational ambivalence.
AB  - OBJECTIVE: The purpose of this study was to examine (a) the extent to which
      widowhood affects older adults' ambivalence about their adult children, (b) the
      role of intergenerational dependence in explaining the effect of widowhood on
      parent-child ambivalence, and (c) temporal changes in the effects of widowhood on
      ambivalence. METHODS: We based analyses on Changing Lives of Older Couples, a
      prospective study of 1,532 married individuals aged 65 and older. We used
      ordinary least squares regression models to estimate the direct effect of
      widowhood and the mediating effects of dependence on intergenerational
      ambivalence 6 and 18 months after spousal loss. RESULT: Widowhood was associated
      with a decrease in ambivalent feelings toward adult children 6 months after
      spousal loss, which was partially explained by a reduction in the extent to which
      children were dependent upon their bereaved parents. However, at 18 months,
      widowhood did not exert any significant influence on intergenerational
      ambivalence. DISCUSSION: Our findings suggest that major life events such as
      widowhood influence intergenerational ambivalence. The results shed light on the
      mechanisms by which parent-child dependence contributes to intergenerational
      ambivalence.

PMID- 18332203
TI  - Predictors of non-local moves among older adults: a prospective study.
AB  - OBJECTIVES: The goal of this article was to test a series of established
      predictors of the hazard of moving for persons primarily in their 50s and 60s. We
      tested demographic covariates, resources, travel experience, and community and
      person ties using a prospective design. METHODS: We employed data from the Health
      and Retirement Study, 1994 to 2002, based on a representative sample of
      households containing at least one member aged 51 to 61 in 1992. We employed
      measures available in the Health and Retirement Study to construct a series of
      Cox proportional hazards models that examined the causes of non-local moves.
      RESULTS: Community and person ties emerged as important predictors of non-local
      moves. DISCUSSION: Travel experience, when measured by regular vacationing and
      second homes, may increase community ties to a destination. The life-course model
      must be modified in its explanation of the importance of community and person
      ties, and of life transitions, as motivators of migration.

PMID- 18332204
TI  - Interleukin-12 and host defense against murine Pneumocystis pneumonia.
AB  - Little is known about the role of the cytokine interleukin-12 (IL-12) in
      Pneumocystis pneumonia or its potential use as immunotherapy. We asked whether
      release of IL-12 is part of the normal host response to this infection and
      whether local treatment with IL-12 or gene transfer of IL-12 could accelerate
      clearance of infection. IL-12 was assayed by enzyme-linked immunosorbent assay in
      normal mice and in mice deficient in IL-12 after inoculation of Pneumocystis
      carinii. P. carinii-infected mice were treated with local instillation of IL-12
      and gene transfer of the IL-12 gene. Inoculation of P. carinii into normal mice
      evoked a brisk release of IL-12 into lung tissue, and IL-12 P35-deficient mice
      showed delayed clearance of infection measured by PCR for P. carinii rRNA. In
      control mice, intranasal recombinant IL-12 accelerated clearance of infection,
      and this was associated with increased recruitment of inflammatory cells into
      lavage fluid and increased release of tumor necrosis factor alpha, IL-12, and
      gamma interferon. Similar results were observed in infected mice depleted of CD4+
      lymphocytes by using in vivo transfer of the IL-12 gene in a replication
      deficient adenoviral vector. IL-12 is part of the normal host response to
      infection with P. carinii. IL-12 therapy can enhance host resistance to infection
      in both normal mice and mice depleted of CD4+ T lymphocytes. A treatment effect
      of IL-12 is mediated through enhanced inflammatory cell recruitment into lung
      tissue and increased tissue concentrations of proinflammatory cytokines.

PMID- 18332205
TI  - Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are
      sufficient to mediate protection against Mycobacterium tuberculosis infection.
AB  - The 10-kDa culture filtrate protein (CFP-10) and 6-kDa early secretory antigen of
      T cells (ESAT-6) are secreted in abundance by Mycobacterium tuberculosis and are
      frequently recognized by T cells from infected people. The genes encoding these
      proteins have been deleted from the genome of the vaccine strain Mycobacterium
      bovis bacillus Calmette-Guerin (BCG), and it is hypothesized that these proteins
      are important targets of protective immunity. Indeed, vaccination with ESAT-6
      elicits protective CD4+ T cells in C57BL/6 mice. We have previously shown that M.
      tuberculosis infection of C3H mice elicits CFP-10-specific CD8+ and CD4+ T cells.
      Here we demonstrate that immunization with a CFP-10 DNA vaccine stimulates a
      specific T-cell response only to the H-2K(k)-restricted epitope CFP-10(32-39).
      These CFP-10(32-39)-specific CD8+ cells undergo a rapid expansion and accumulate
      in the lung following challenge of immunized mice with aerosolized M.
      tuberculosis. Protective immunity is induced by CFP-10 DNA vaccination as
      measured by a CFU reduction in the lung and spleen 4 and 8 weeks after challenge
      with M. tuberculosis. These data demonstrate that CFP-10 is a protective antigen
      and that CFP-10(32-39)-specific CD8+ T cells elicited by vaccination are
      sufficient to mediate protection against tuberculosis.

PMID- 18332206
TI  - Single nucleotide polymorphisms that cause structural changes in the cyclic AMP
      receptor protein transcriptional regulator of the tuberculosis vaccine strain
      Mycobacterium bovis BCG alter global gene expression without attenuating growth.
AB  - Single nucleotide polymorphisms (SNPs) are present in the global transcriptional
      regulator cyclic AMP (cAMP) receptor protein (CRP) of the attenuated vaccine
      strain Mycobacterium bovis, bacillus Calmette-Guerin (BCG). We have found that
      these SNPs resulted in small but significant changes in the expression of a
      number of genes in M. tuberculosis when a deletion of the Rv3676 CRP was
      complemented by the BCG allele, compared to complementation by the M.
      tuberculosis allele. We can explain these changes in gene expression by modeling
      the structure of the mycobacterial protein on the known structure of CRP from
      Escherichia coli. Thus, the SNP change in the DNA-binding domain, Lys178, is
      predicted to form a hydrogen bond with the phosphate backbone of the DNA, as does
      the equivalent residue in E. coli, whereas Glu178 in M. tuberculosis/M. bovis
      does not, thus explaining the stronger binding reported for CRP of BCG to CRP
      binding sites in mycobacterial DNA. In contrast, the SNP change in the nucleotide
      binding domain (Leu47Pro) is predicted to result in the loss of one hydrogen
      bond, which is accommodated by the structure, and would not therefore be expected
      to cause any change in function relating to cAMP binding. The BCG allele fully
      complemented the growth defect caused by the deletion of the Rv3676 protein in M.
      tuberculosis, both in vitro and in macrophage and mouse infections, suggesting
      that these SNPs do not play any role in the attenuation of BCG. However, they may
      have allowed BCG to grow better under the in vitro-selective conditions used in
      its derivation from the M. bovis wild type.

PMID- 18332207
TI  - The Staphyloccous aureus Eap protein activates expression of proinflammatory
      cytokines.
AB  - The extracellular adhesion protein (Eap) secreted by the major human pathogen
      Staphylococcus aureus is known to have several effects on human immunity. We have
      recently added to knowledge of these roles by demonstrating that Eap enhances
      interactions between major histocompatibility complex molecules and human
      leukocytes. Several studies have indicated that Eap can induce cytokine
      production by human peripheral blood mononuclear cells (PBMCs). To date, there
      has been no rigorous attempt to identify the breadth of cytokines produced by Eap
      stimulation or to identify the cell subsets that respond. Here, we demonstrate
      that Eap induces the secretion of the proinflammatory cytokines interleukin 6 (IL
      6) and tumor necrosis factor alpha (TNF-alpha) by CD14(+) leukocytes (monocytes
      and macrophages) within direct ex vivo PBMC populations (note that granulocytes
      are also CD14(+) but are largely depleted from PBMC preparations). Anti
      intercellular adhesion molecule 1 (CD54) antibodies inhibited this induction and
      implicated a role for this known Eap binding protein in cellular activation. IL-6
      and TNF-alpha secretion by murine cells exposed to Eap was also observed. The
      activation of CD14(+) cells by Eap suggests that it could play a significant role
      in both septic shock and fever, two of the major pathological features of S.
      aureus infections.

PMID- 18332208
TI  - Toll-like receptor 9-dependent immune activation by unmethylated CpG motifs in
      Aspergillus fumigatus DNA.
AB  - Phagocytic defenses are critical for effective host defenses against the
      opportunistic fungal pathogen Aspergillus fumigatus. Previous studies found that
      following challenge with A. fumigatus, Toll-like receptor 9 (TLR9) knockout mice
      survived longer than wild-type mice. However, the mechanism responsible was not
      defined. Here we demonstrate that A. fumigatus contains unmethylated CpG
      sequences, the natural ligands for TLR9. A. fumigatus DNA and synthetic CpG-rich
      oligodeoxynucleotides (ODNs) containing sequences found in the A. fumigatus
      genome potently stimulated the production of proinflammatory cytokines in mouse
      bone marrow-derived dendritic cells (BMDCs) and human plasmacytoid dendritic
      cells. The response was decreased when the fungal DNA was treated with a CpG
      methylase or with CpG-specific endonucleases. A role for TLR9 was demonstrated as
      cytokine production was abolished in BMDCs from TLR9-deficient mice. Moreover,
      transfection of HEK293 cells with human TLR9 conferred responsiveness to
      synthetic CpG-rich ODNs containing sequences found in A. fumigatus DNA. Taken
      together, these data demonstrate that TLR9 detects A. fumigatus DNA, resulting in
      the secretion of proinflammatory cytokines, which may contribute to the immune
      response to the pathogen.

PMID- 18332209
TI  - The intrinsic immunoglobulin g endopeptidase activity of streptococcal Mac-2
      proteins implies a unique role for the enzymatically impaired Mac-2 protein of
      M28 serotype strains.
AB  - IdeS, a secreted cysteine protease of the important human pathogen Streptococcus
      pyogenes, interferes with phagocytic killing by specifically cleaving the heavy
      chain of immunoglobulin G (IgG). Two allelic variants of the enzyme have been
      described, the IgG-specific endopeptidase, IdeS (or Mac-1) and Mac-2, a protein
      with only weak IgG endopeptidase activity, which has been suggested to interfere
      with opsonophagocytosis by blocking Fcgamma receptors of phagocytic cells.
      However, despite the fact that Mac-2 proteins interact with Fcgamma receptors, no
      inhibition of reactive oxygen species (ROS) production, opsonophagocytosis, or
      streptococcal killing by Mac-2 has been reported. In the present study, Mac-2
      proteins are shown to contain IgG endopeptidase activity indistinguishable from
      the enzymatic activity exhibited by IdeS/Mac-1 proteins. The earlier reported
      weak IgG endopeptidase activity appears to be unique to Mac-2 of M28 serotype
      strains (Mac-2(M28)) and is most likely due to the formation of a disulfide bond
      between the catalytic site cysteine and a cysteine residue in position 257 of Mac
      2(M28). Furthermore, Mac-2 proteins are shown to inhibit ROS production ex vivo,
      independently of the IgG endopeptidase activity of the proteins. Inhibition of
      ROS generation per se, however, was not sufficient to mediate streptococcal
      survival in bactericidal assays. Thus, in contrast to earlier studies,
      implicating separate functions for IdeS and Mac-2 protein variants, the current
      study suggests that Mac-2 and IdeS are bifunctional proteins, combining Fcgamma
      receptor binding and IgG endopeptidase activity. This finding implies a unique
      role for Mac-2 proteins of the M28 serotype, since this serotype has evolved and
      retained a Mac-2 protein lacking IgG endopeptidase activity.

PMID- 18332210
TI  - A tightly regulated surface protein of Borrelia burgdorferi is not essential to
      the mouse-tick infectious cycle.
AB  - Borrelia burgdorferi synthesizes a variety of differentially regulated outer
      surface lipoproteins in the tick vector and in vertebrate hosts. Among these is
      OspD, a protein that is highly induced in vitro by conditions that mimic the tick
      environment. Using genetically engineered strains in which ospD is deleted, we
      demonstrate that this protein is not required for B. burgdorferi survival and
      infectivity in either the mouse or the tick. However, examination of both
      transcript levels and protein expression indicates that OspD expression is
      limited to a discrete window of time during B. burgdorferi replication within the
      tick. This time frame corresponds to tick detachment from the host following
      feeding, and expression of OspD continues during tick digestion of the blood meal
      but is low or undetectable after the tick has molted. The high level of OspD
      production correlates to the highest cell densities that B. burgdorferi is known
      to reach in vivo. Although OspD is nonessential to the infectious cycle of B.
      burgdorferi, the tight regulation of expression suggests a beneficial
      contribution of OspD to the spirochete during bacterial replication within the
      tick midgut.

PMID- 18332211
TI  - Interleukin-1beta modulates proinflammatory cytokine production in human
      epithelial cells.
AB  - Periodontitis is a chronic human inflammatory disease initiated and sustained by
      dental plaque microorganisms. A major contributing pathogen is Porphyromonas
      gingivalis, a gram-negative bacterium recognized by Toll-like receptor 2 (TLR2)
      and TLR4, which are expressed by human gingival epithelial cells (HGECs).
      However, it is still unclear how these cells respond to P. gingivalis and
      initiate inflammatory and immune responses. We have reported previously that
      HGECs produce a wide range of proinflammatory cytokines, including interleukin-6
      (IL-6), IL-8, granulocyte-macrophage colony-stimulating factor, tumor necrosis
      factor alpha (TNF-alpha), and IL-1beta. In this study, we show that IL-1beta has
      a special role in the modulation of other inflammatory cytokines in HGECs
      challenged with P. gingivalis. Our results show that the increased production of
      IL-1beta correlates with the cell surface expression of TLR4, and more
      specifically, TLR4-normal HGECs produce fourfold more IL-1beta than do TLR4
      deficient HGECs after challenge. Moreover, blocking the IL-1beta receptor greatly
      reduces the production of "secondary" proinflammatory cytokines such as IL-8 or
      IL-6. Our data indicate that the induction of IL-1beta plays an important role in
      mediating the release of other proinflammatory cytokines from primary human
      epithelial cells following challenge with P. gingivalis, and this process may be
      an inflammatory enhancement mechanism adopted by epithelial cells.

PMID- 18332212
TI  - A novel Treponema pallidum antigen, TP0136, is an outer membrane protein that
      binds human fibronectin.
AB  - The antigenicity, structural location, and function of the predicted lipoprotein
      TP0136 of Treponema pallidum subsp. pallidum were investigated based on previous
      screening studies indicating that anti-TP0136 antibodies are present in the sera
      of syphilis patients and experimentally infected rabbits. Recombinant TP0136
      (rTP0136) protein was purified and shown to be strongly antigenic during human
      and experimental rabbit infection. The TP0136 protein was exposed on the surface
      of the bacterial outer membrane and bound to the host extracellular matrix
      glycoproteins fibronectin and laminin. In addition, the TP0136 open reading frame
      was shown to be highly polymorphic among T. pallidum subspecies and strains at
      the nucleotide and amino acid levels. Finally, the ability of rTP0136 protein to
      act as a protective antigen to subsequent challenge with infectious T. pallidum
      in the rabbit model of infection was assessed. Immunization with rTP0136 delayed
      ulceration but did not prevent infection or the formation of lesions. These
      results demonstrate that TP0136 is expressed on the outer membrane of the
      treponeme during infection and may be involved in attachment to host
      extracellular matrix components.

PMID- 18332213
TI  - Macrophages are mediators of gastritis in acute Helicobacter pylori infection in
      C57BL/6 mice.
AB  - Helicobacter pylori is the etiological agent of human chronic gastritis, a
      condition seen as a precursor to the development of gastrointestinal ulcers or
      gastric cancer. This study utilized the murine model of chronic H. pylori
      infection to characterize the role of macrophages in the induction of specific
      immune responses and gastritis and in the control of the bacterial burden
      following H. pylori infection and vaccination. Drug-loaded liposomes were
      injected intravenously to deplete macrophages from C57BL/6 mice, and effective
      removal of CD11b+ cells from the spleens and stomachs of mice was confirmed by
      immunofluorescence microscopy. Transient elimination of macrophages from C57BL/6
      mice during the early period of infection reduced the gastric pathology induced
      by H. pylori SS1 but did not affect the bacterial load in the stomach. These data
      suggest that macrophages are important to the severity of gastric inflammation
      during H. pylori infection.

PMID- 18332214
TI  - Intravaginal immunization of mice with recombinant Salmonella enterica serovar
      Typhimurium expressing human papillomavirus type 16 antigens as a potential route
      of vaccination against cervical cancer.
AB  - Cervical cancer, the second leading cause of cancer deaths in women, is the
      consequence of high-risk human papillomavirus (HPV) infections. Toward the
      development of therapeutic vaccines that can induce both innate and adaptive
      mucosal immune responses, we analyzed intravaginal (ivag) vaccine delivery of
      live attenuated Salmonella enterica serovar Typhimurium expressing HPV16L1 as a
      model antigen. Innate immune responses were examined in cervicovaginal tissues by
      determining gene expression patterns by microarray analysis using nylon membranes
      imprinted with cDNA fragments coding for inflammation-associated genes. At 24 h,
      a wide range of genes, including those for chemokines and Th1- and Th2-type
      cytokine and chemokine receptors were up-regulated in mice ivag immunized with
      Salmonella compared to control mice. However, the majority of transcripts
      returned to their steady-state levels 1 week after immunization, suggesting a
      transient inflammatory response. Indeed, cervicovaginal histology of immunized
      mice showed a massive, but transient, infiltration of macrophages and
      neutrophils, while T cells were still increased after 7 days. Ivag immunization
      also induced humoral and antitumor immune responses, i.e., serum and vaginal anti
      HPV16VLP antibody titers similar to those induced by oral immunization, and
      significant protection in tumor protection experiments using HPV16-expressing C3
      tumor cells. These results show that ivag immunization with live attenuated
      Salmonella expressing HPV16 antigens modulates the local mucosal gene expression
      pattern into a transient proinflammatory profile, elicits strong systemic and
      mucosal immunity against HPV16, and confers protection against HPV16 tumor cells
      subcutaneously implanted in mice. Examination of the efficacy with which ivag
      HPV16E7E6 Salmonella induces regression of tumors located in cervicovaginal
      tissue is warranted.

PMID- 18332215
TI  - Jennifer Zallen: decoding the developmental dance. Interview by Ruth Williams.

PMID- 18332216
TI  - Human embryonic stem cells in culture possess primary cilia with hedgehog
      signaling machinery.
AB  - Human embryonic stem cells (hESCs) are potential therapeutic tools and models of
      human development. With a growing interest in primary cilia in signal
      transduction pathways that are crucial for embryological development and tissue
      differentiation and interest in mechanisms regulating human hESC differentiation,
      demonstrating the existence of primary cilia and the localization of signaling
      components in undifferentiated hESCs establishes a mechanistic basis for the
      regulation of hESC differentiation. Using electron microscopy (EM),
      immunofluorescence, and confocal microscopies, we show that primary cilia are
      present in three undifferentiated hESC lines. EM reveals the characteristic 9 + 0
      axoneme. The number and length of cilia increase after serum starvation.
      Important components of the hedgehog (Hh) pathway, including smoothened, patched
      1 (Ptc1), and Gli1 and 2, are present in the cilia. Stimulation of the pathway
      results in the concerted movement of Ptc1 out of, and smoothened into, the
      primary cilium as well as up-regulation of GLI1 and PTC1. These findings show
      that hESCs contain primary cilia associated with working Hh machinery.

PMID- 18332217
TI  - The regulation of SIRT2 function by cyclin-dependent kinases affects cell
      motility.
AB  - Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes,
      including cell cycle progression and cytoskeletal dynamics. A limited number of
      Cdk substrates have been identified with few demonstrated to be regulated by Cdk
      dependent phosphorylation. We identify on protein expression arrays novel cyclin
      E-Cdk2 substrates, including SIRT2, a member of the Sirtuin family of NAD(+)
      dependent deacetylases that targets alpha-tubulin. We define Ser-331 as the site
      phosphorylated by cyclin E-Cdk2, cyclin A-Cdk2, and p35-Cdk5 both in vitro and in
      cells. Importantly, phosphorylation at Ser-331 inhibits the catalytic activity of
      SIRT2. Gain- and loss-of-function studies demonstrate that SIRT2 interfered with
      cell adhesion and cell migration. In postmitotic hippocampal neurons, neurite
      outgrowth and growth cone collapse are inhibited by SIRT2. The effects provoked
      by SIRT2, but not those of a nonphosphorylatable mutant, are antagonized by Cdk
      dependent phosphorylation. Collectively, our findings identify a
      posttranslational mechanism that controls SIRT2 function, and they provide
      evidence for a novel regulatory circuitry involving Cdks, SIRT2, and
      microtubules.

PMID- 18332218
TI  - Essential role of B-Raf in oligodendrocyte maturation and myelination during
      postnatal central nervous system development.
AB  - Mutations in the extracellular signal-regulated kinase (ERK) pathway,
      particularly in the mitogen-activated protein kinase/ERK kinase (MEK) activator B
      Raf, are associated with human tumorigenesis and genetic disorders. Hence, B-Raf
      is a prime target for molecule-based therapies, and understanding its essential
      biological functions is crucial for their success. B-Raf is expressed
      preferentially in cells of neuronal origin. Here, we show that in mice,
      conditional ablation of B-Raf in neuronal precursors leads to severe
      dysmyelination, defective oligodendrocyte differentiation, and reduced ERK
      activation in brain. Both B-Raf ablation and chemical inhibition of MEK impair
      oligodendrocyte differentiation in vitro. In glial cell cultures, we find B-Raf
      in a complex with MEK, Raf-1, and kinase suppressor of Ras. In B-Raf-deficient
      cells, more Raf-1 is recruited to MEK, yet MEK/ERK phosphorylation is impaired.
      These data define B-Raf as the rate-limiting MEK/ERK activator in oligodendrocyte
      differentiation and myelination and have implications for the design and use of
      Raf inhibitors.

PMID- 18332219
TI  - Calpain 2 and PTP1B function in a novel pathway with Src to regulate invadopodia
      dynamics and breast cancer cell invasion.
AB  - Invasive cancer cells form dynamic adhesive structures associated with matrix
      degradation called invadopodia. Calpain 2 is a calcium-dependent intracellular
      protease that regulates adhesion turnover and disassembly through the targeting
      of specific substrates such as talin. Here, we describe a novel function for
      calpain 2 in the formation of invadopodia and in the invasive abilities of breast
      cancer cells through the modulation of endogenous c-Src activity. Calpain
      deficient breast cancer cells show impaired invadopodia formation that is rescued
      by expression of a truncated fragment of protein tyrosine phosphatase 1B (PTP1B)
      corresponding to the calpain proteolytic fragment, which indicates that calpain
      modulates invadopodia through PTP1B. Moreover, PTP1B activity is required for
      efficient invadopodia formation and breast cancer invasion, which suggests that
      PTP1B may modulate breast cancer progression through its effects on invadopodia.
      Collectively, our experiments implicate a novel signaling pathway involving
      calpain 2, PTP1B, and Src in the regulation of invadopodia and breast cancer
      invasion.

PMID- 18332220
TI  - Inhibition of "self" engulfment through deactivation of myosin-II at the
      phagocytic synapse between human cells.
AB  - Phagocytosis of foreign cells or particles by macrophages is a rapid process that
      is inefficient when faced with "self" cells that display CD47-although signaling
      mechanisms in self-recognition have remained largely unknown. With human
      macrophages, we show the phagocytic synapse at cell contacts involves a basal
      level of actin-driven phagocytosis that, in the absence of species-specific CD47
      signaling, is made more efficient by phospho-activated myosin. We use "foreign"
      sheep red blood cells (RBCs) together with CD47-blocked, antibody-opsonized human
      RBCs in order to visualize synaptic accumulation of phosphotyrosine, paxillin, F
      actin, and the major motor isoform, nonmuscle myosin-IIA. When CD47 is
      functional, the macrophage counter-receptor and phosphatase-activator SIRPalpha
      localizes to the synapse, suppressing accumulation of phosphotyrosine and myosin
      without affecting F-actin. On both RBCs and microbeads, human CD47 potently
      inhibits phagocytosis as does direct inhibition of myosin. CD47-SIRPalpha
      interaction initiates a dephosphorylation cascade directed in part at
      phosphotyrosine in myosin. A point mutation turns off this motor's contribution
      to phagocytosis, suggesting that self-recognition inhibits contractile
      engulfment.

PMID- 18332221
TI  - Myoblasts and macrophages share molecular components that contribute to cell-cell
      fusion.
AB  - Cell-cell fusion is critical to the normal development of certain tissues, yet
      the nature and degree of conservation of the underlying molecular components
      remains largely unknown. Here we show that the two guanine-nucleotide exchange
      factors Brag2 and Dock180 have evolutionarily conserved functions in the fusion
      of mammalian myoblasts. Their effects on muscle cell formation are distinct and
      are a result of the activation of the GTPases ARF6 and Rac, respectively.
      Inhibition of ARF6 activity results in a lack of physical association between
      paxillin and beta(1)-integrin, and disruption of paxillin transport to sites of
      focal adhesion. We show that fusion machinery is conserved among distinct cell
      types because Dock180 deficiency prevented fusion of macrophages and the
      formation of multinucleated giant cells. Our results are the first to demonstrate
      a role for a single protein in the fusion of two different cell types, and
      provide novel mechanistic insight into the function of GEFs in the morphological
      maturation of multinucleated cells.

PMID- 18332222
TI  - Important role of matrix metalloproteinase 9 in epileptogenesis.
AB  - Temporal lobe epilepsy (TLE) is a devastating disease in which aberrant synaptic
      plasticity plays a major role. We identify matrix metalloproteinase (MMP) 9 as a
      novel synaptic enzyme and a key pathogenic factor in two animal models of TLE:
      kainate-evoked epilepsy and pentylenetetrazole (PTZ) kindling-induced epilepsy.
      Notably, we show that the sensitivity to PTZ epileptogenesis is decreased in MMP
      9 knockout mice but is increased in a novel line of transgenic rats
      overexpressing MMP-9. Immunoelectron microscopy reveals that MMP-9 associates
      with hippocampal dendritic spines bearing asymmetrical (excitatory) synapses,
      where both the MMP-9 protein levels and enzymatic activity become strongly
      increased upon seizures. Further, we find that MMP-9 deficiency diminishes
      seizure-evoked pruning of dendritic spines and decreases aberrant synaptogenesis
      after mossy fiber sprouting. The latter observation provides a possible
      mechanistic basis for the effect of MMP-9 on epileptogenesis. Our work suggests
      that a synaptic pool of MMP-9 is critical for the sequence of events that
      underlie the development of seizures in animal models of TLE.

PMID- 18332223
TI  - Integrin-linked kinase stabilizes myotendinous junctions and protects muscle from
      stress-induced damage.
AB  - Skeletal muscle expresses high levels of integrin-linked kinase (ILK),
      predominantly at myotendinous junctions (MTJs) and costameres. ILK binds the
      cytoplasmic domain of beta1 integrin and mediates phosphorylation of protein
      kinase B (PKB)/Akt, which in turn plays a central role during skeletal muscle
      regeneration. We show that mice with a skeletal muscle-restricted deletion of ILK
      develop a mild progressive muscular dystrophy mainly restricted to the MTJs with
      detachment of basement membranes and accumulation of extracellular matrix.
      Endurance exercise training enhances the defects at MTJs, leads to disturbed
      subsarcolemmal myofiber architecture, and abrogates phosphorylation of Ser473 as
      well as phosphorylation of Thr308 of PKB/Akt. The reduction in PKB/Akt activation
      is accompanied by an impaired insulin-like growth factor 1 receptor (IGF-1R)
      activation. Coimmunoprecipitation experiments reveal that the beta1 integrin
      subunit is associated with the IGF-1R in muscle cells. Our data identify the
      beta1 integrin-ILK complex as an important component of IGF-1R/insulin receptor
      substrate signaling to PKB/Akt during mechanical stress in skeletal muscle.

PMID- 18332224
TI  - Why are literature data for H2O2 contents so variable? A discussion of potential
      difficulties in the quantitative assay of leaf extracts.
AB  - Leaf metabolism produces H2O2 at high rates, but current concepts suggest that
      the potent signalling effects of this oxidant require that concentrations be
      controlled by a battery of antioxidative enzymes. The extent to which H2O2 is
      allowed to accumulate remains unclear. There is little consensus on leaf H2O2
      values in the literature and measured concentrations in unstressed conditions
      range from 50-5000 nmol g(-1) fresh weight, a difference that probably reflects
      technical inaccuracies as much as biological variability. This article uses new
      experimental and literature data to examine some of the difficulties in
      accurately measuring H2O2 in leaf extracts. Potential problems relate to
      sensitivity, interference from other redox-active compounds, and H2O2 stability
      during sample preparation. Particular attention is drawn to the influence of
      tissue mass/extraction volume in the quantitative estimation of H2O2 contents,
      and the possibility that this factor could contribute to the variability of
      literature data.

PMID- 18332225
TI  - Nitric oxide, stomatal closure, and abiotic stress.
AB  - Various data indicate that nitric oxide (NO) is an endogenous signal in plants
      that mediates responses to several stimuli. Experimental evidence in support of
      such signalling roles for NO has been obtained via the application of NO, usually
      in the form of NO donors, via the measurement of endogenous NO, and through the
      manipulation of endogenous NO content by chemical and genetic means. Stomatal
      closure, initiated by abscisic acid (ABA), is effected through a complex symphony
      of intracellular signalling in which NO appears to be one component. Exogenous NO
      induces stomatal closure, ABA triggers NO generation, removal of NO by scavengers
      inhibits stomatal closure in response to ABA, and ABA-induced stomatal closure is
      reduced in mutants that are impaired in NO generation. The data indicate that ABA
      induced guard cell NO generation requires both nitric oxide synthase-like
      activity and, in Arabidopsis, the NIA1 isoform of nitrate reductase (NR). NO
      stimulates mitogen-activated protein kinase (MAPK) activity and cGMP production.
      Both these NO-stimulated events are required for ABA-induced stomatal closure.
      ABA also stimulates the generation of H2O2 in guard cells, and pharmacological
      and genetic data demonstrate that NO accumulation in these cells is dependent on
      such production. Recent data have extended this model to maize mesophyll cells
      where the induction of antioxidant defences by water stress and ABA required the
      generation of H2O2 and NO and the activation of a MAPK. Published data suggest
      that drought and salinity induce NO generation which activates cellular processes
      that afford some protection against the oxidative stress associated with these
      conditions. Exogenous NO can also protect cells against oxidative stress. Thus,
      the data suggest an emerging model of stress responses in which ABA has several
      ameliorative functions. These include the rapid induction of stomatal closure to
      reduce transpirational water loss and the activation of antioxidant defences to
      combat oxidative stress. These are two processes that both involve NO as a key
      signalling intermediate.

PMID- 18332226
TI  - Hexoses as phloem transport sugars: the end of a dogma?
AB  - According to most textbooks, only non-reducing carbohydrate species such as
      sucrose, sugar alcohols, and raffinose-family sugars function as phloem
      translocates. Occasional abundance of reducing sugar species (such as hexoses) in
      sieve-tube sap has been discarded as an experimental artefact. This study,
      however, discloses a widespread occurrence of hexoses in the sieve-tube sap.
      Phloem exudation facilitated by EDTA provided evidence that many of the members
      of two plant families (Ranunculaceae and Papaveraceae) investigated translocate
      >80% of carbohydrates in the form of hexoses. Representatives of other families
      also appear to translocate appreciable amounts of hexoses in the sieve tubes.
      Promoting effects of EDTA, activities of sucrose-degrading enzymes, and sugar
      uptake by micro-organisms on hexose contents of phloem exudates were checked. The
      rate of sucrose degradation is far too low to explain the large proportions of
      hexoses measured in phloem exudates; nor did other factors tested seem to
      stimulate the occurrence of hexoses. The validity of the approach is further
      supported by the virtual absence of hexoses in exudates from species that were
      known as exclusive sucrose transporters. This study urges a rethink of the
      existing views on carbohydrate transport species in the phloem stream. Hexose
      translocation is to be regarded as a normal mode of carbohydrate transfer by the
      phloem equivalent to that of sucrose, raffinose-family sugars, or sugar alcohols.

PMID- 18332227
TI  - Meristem identity gene expression during curd proliferation and flower initiation
      in Brassica oleracea.
AB  - The regulation of reproductive development in cauliflower (Brassica oleracea var.
      botrytis DC) and broccoli (B. oleracea L. var. italica Plenck) is unusual in that
      most enlargement occurs while development is arrested at a distinct stage.
      Cauliflower and broccoli curds are composed of inflorescence meristems and flower
      buds, respectively. To determine whether this arrest is maintained by altered
      expression of the genes that specify these steps in Arabidopsis, the expression
      of each copy of their homologues (MADS-box genes BoAP1-a, BoAP1-c, BoCAL, BoFUL
      a, BoFUL-b, BoFUL-c, and BoFUL-d; and non-MADS-box genes BoLFY, AP2, UFO, and
      BoTFL1) and the cauliflower curd-specific genes CCE1 and BoREM1 were measured
      simultaneously in heads that were arrested at different developmental stages by
      varying temperature, but had a common genotype. Transcript abundance of BoFUL
      paralogues and BoLFY was highest at the cauliflower stage of arrest, consistent
      with these genes initiating inflorescence meristems. The expression of other
      genes was the same regardless of the developmental stage of arrest. The expected
      models can therefore be excluded, wherein maintenance of arrest at the
      inflorescence meristem is a consequence of suppression of BoCAL, BoAP1-a, or
      BoLFY, or failure to suppress BoTFL1. Floral primordia and floral buds were
      normal in boap1-a boap1-c bocal triple mutants; therefore, other meristem
      identity genes can specify floral initiation (A-function) in B. oleracea. BoTFL1,
      a strong repressor of flowering in Arabidopsis, did not suppress the formation of
      the floral primordium in B. oleracea. Initiation of floral primordia and
      enlargement of floral buds in broccoli and cauliflower is not controlled solely
      by homologues of the genes that do so in Arabidopsis.

PMID- 18332228
TI  - PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of
      mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and
      signaling pathways important in differentiation of MSCs into adipogenic,
      chondrogenic, and osteogenic lineages.
AB  - We compared the transcriptomes of marrow-derived mesenchymal stem cells (MSCs)
      with differentiated adipocytes, osteocytes, and chondrocytes derived from these
      MSCs. Using global gene-expression profiling arrays to detect RNA transcripts, we
      have identified markers that are specific for MSCs and their differentiated
      progeny. Further, we have also identified pathways that MSCs use to differentiate
      into adipogenic, chondrogenic, and osteogenic lineages. We identified activin
      mediated transforming growth factor (TGF)-beta signaling, platelet-derived growth
      factor (PDGF) signaling and fibroblast growth factor (FGF) signaling as the key
      pathways involved in MSC differentiation. The differentiation of MSCs into these
      lineages is affected when these pathways are perturbed by inhibitors of cell
      surface receptor function. Since growth and differentiation are tightly linked
      processes, we also examined the importance of these 3 pathways in MSC growth.
      These 3 pathways were necessary and sufficient for MSC growth. Inhibiting any of
      these pathways slowed MSC growth, whereas a combination of TGF-beta, PDGF, and
      beta-FGF was sufficient to grow MSCs in a serum-free medium up to 5 passages.
      Thus, this study illustrates it is possible to predict signaling pathways active
      in cellular differentiation and growth using microarray data and experimentally
      verify these predictions.

PMID- 18332229
TI  - Unprecedented diversity of genotypic revertants in lymphocytes of a patient with
      Wiskott-Aldrich syndrome.
AB  - Spontaneous somatic reversions of inherited mutations are poorly understood
      phenomena that are thought to occur uncommonly in a variety of genetic disorders.
      When molecularly characterized, revertant cells have rarely exhibited more than
      one revertant genotype per patient. We analyzed individual allospecific T-cell
      clones derived from a Wiskott-Aldrich syndrome (WAS) patient identified by flow
      cytometry to have 10% to 15% revertant, WAS protein-expressing lymphocytes in his
      blood. Genotypic analysis of the clones revealed a remarkable diversity of
      deletions and base substitutions resulting in at least 34 different revertant
      genotypes that restored expression of WASp. A large fraction of these revertant
      genotypes were also identified in primary T cells purified from peripheral blood.
      These data suggest that the use of sensitive methods may reveal the presence of
      wide arrays of individual genotypic revertants in WAS patients and offer
      opportunities for further understanding of their occurrence.

PMID- 18332230
TI  - Multiple myeloma.
AB  - Multiple myeloma is a clonal plasma cell malignancy that accounts for slightly
      more than 10% of all hematologic cancers. In this paper, we present a
      historically focused review of the disease, from the description of the first
      case in 1844 to the present. The evolution of drug therapy and stem-cell
      transplantation for the treatment of myeloma, as well as the development of new
      agents, is discussed. We also provide an update on current concepts of diagnosis
      and therapy, with an emphasis on how treatments have emerged from a historical
      perspective after certain important discoveries and the results of experimental
      studies.

PMID- 18332231
TI  - Bovine protein disulfide isomerase-enhanced tissue factor coagulant function: is
      phospholipid contaminant in it the real culprit?

PMID- 18332232
TI  - Aberrant Ikaros, Aiolos, and Helios expression in Hodgkin and non-Hodgkin
      lymphoma.

PMID- 18332233
TI  - Eliminating the complete response penalty from myeloma response assessment.

PMID- 18332234
TI  - Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte
      differentiation.
AB  - CD14+ peripheral blood monocytes can differentiate into fibroblast-like cells
      called fibrocytes, which are associated with and are at least partially
      responsible for wound healing and fibrosis in multiple organ systems. Signals
      regulating fibrocyte differentiation are poorly understood. In this study, we
      find that when added to human PBMCs cultured in serum-free medium, the
      profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without
      inducing fibrocyte or fibrocyte precursor proliferation. We also find that the
      potent, antifibrotic cytokines IFN-gamma and IL-12 inhibit fibrocyte
      differentiation. In our culture system, IL-1beta, IL-3, IL-6, IL-7, IL-16, GM
      CSF, M-CSF, fetal liver tyrosine kinase 3, insulin growth factor 1, vascular
      endothelial growth factor, and TNF-alpha had no significant effect on fibrocyte
      differentiation. IL-4, IL-13, and IFN-gamma act directly on monocytes to regulate
      fibrocyte differentiation, and IL-12 acts indirectly, possibly through CD16
      positive NK cells. We previously identified the plasma protein serum amyloid P
      (SAP) as a potent inhibitor of fibrocyte differentiation. When added together,
      the fibrocyte-inhibitory activity of SAP dominates the profibrocyte activities of
      IL-4 and IL-13. The profibrocyte activities of IL-4 and IL-13 and the fibrocyte
      inhibitory activities of IFN-gamma and IL-12 counteract each other in a
      concentration-dependent manner. These results indicate that the complex mix of
      cytokines and plasma proteins present in inflammatory lesions, wounds, and
      fibrosis will influence fibrocyte differentiation.

PMID- 18332235
TI  - Montelukast inhibition of resting and GM-CSF-stimulated eosinophil adhesion to
      VCAM-1 under flow conditions appears independent of cysLT(1)R antagonism.
AB  - Montelukast (MLK) is a cysteinyl leukotriene receptor-1 (cysLT(1)R) antagonist
      with inhibitory effects on eosinophils, key proinflammatory cells in asthma. We
      assessed the effect of MLK on resting and GM-CSF-stimulated eosinophil adhesion
      to recombinant human (rh)VCAM-1 at different flow rates using our novel microflow
      system. At 1 or 2 dyn cm(-2), shear-stress unstimulated eosinophils tethered
      immediately to rhVCAM-1, "rolled" along part of the channel until they tethered,
      or rolled without tethering. At flow rates greater than 2 dyn cm(-2), adherent
      eosinophils began to be displaced from rhVCAM-1. MLK (10 nM and 100 nM) gave
      partial ( approximately 40%) but significant (P<0.05) inhibition of unstimulated
      eosinophil adhesion to rhVCAM-1 at 1 or 2 dyn cm(-2) shear stress. Once adhered,
      unstimulated eosinophils did not exhibit morphological changes, and GM-CSF
      stimulated eosinophil adhesion under flow was characterized by greater cell
      flattening with significant (P<0.05) inhibition of adherent cell numbers by 100
      nM MLK observed. This effect appeared specific for MLK, as the analog (E)-3-[[[3
      [2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-[[3-dimethylamino)-3
      oxopropyl]thio]methyl]thio]-propanoic acid, sodium salt, had no significant
      effect on eosinophil adhesion to VCAM-1. The possibility that LTC(4), released
      from unstimulated or GM-CSF-treated eosinophils, contributed to their adhesion to
      VCAM-1 was excluded as the LT biosynthesis inhibitor 3-[1-(p-Chlorobenzyl)-5
      (isopropyl)-3-t-butylthioindol-2-yl]-2,2-dimethylpropanoic acid had no inhibitory
      effect, and exogenously added LTC(4) did not enhance eosinophil adhesion. In
      contrast, LTD(4) enhanced eosinophil adhesion to VCAM-1, an effect blocked by MLK
      (10 and 100 nM). These findings demonstrate that MLK-mediated inhibition of
      unstimulated and GM-CSF-stimulated eosinophil adhesion to VCAM-1 under shear
      stress conditions appears independent of cysLT(1)R antagonism.

PMID- 18332236
TI  - Expression of Fox head protein 1 in human eutopic endometrium and endometriosis.
AB  - The objective of this study is to examine the localization and expression of
      FOXP1 in human endometrium during the menstrual cycle and in endometriotic
      lesions and endometrial adenocarcinoma. FOXP1 protein expression was analyzed by
      immunohistochemistry and Western blot. FOXP1 expression was significantly
      different between glandular epithelial and stromal nuclei and cytoplasm in both
      endometrial functionalis and basalis. FOXP1 immunostaining was significantly
      reduced in the early secretory stage in comparison to the mid proliferative stage
      in the functionalis and the early proliferative stage in the basalis. FOXP1
      expression was found in endometriotic lesions but not in endometrial
      adenocarcinoma. Multiple protein bands of FOXP1 were identified, and their
      presence varied considerably among patients. Protein expression levels were
      significantly higher in the mid and late secretory stages in comparison to early
      proliferative and early secretory stages. FOXP1 protein is present in human
      endometrium with evidence of cycle stage-dependent changes in expression.

PMID- 18332237
TI  - The effect of maternal body condition score before and during pregnancy on the
      glucose tolerance of adult sheep offspring.
AB  - This study investigates the effects of diet-induced changes in maternal body
      condition on glucose tolerance in sheep. Welsh Mountain ewes were established, by
      dietary manipulation, at a body condition score of 2 (lower body condition
      [LBCS], n = 17) or >3 (higher body condition [HBCS], n = 19) prior to and during
      pregnancy. Birth weight and postnatal growth were similar in LBCS and HBCS
      offspring. In young adulthood, LBCS offspring had increased fasting glucose
      levels (3.8 +/- 0.07 vs 3.6 +/- 0.05 mM, P < .05), poorer glucose tolerance (2274
      +/- 22.6 vs 2161 +/- 33 min/mM, P < .01), and reduced insulin secretion (0.58 +/-
      0.05 vs 0.71 +/- 0.07 nM/min, P = .07). Increased fasting glycemia, mild glucose
      intolerance, and impaired initial insulin secretory response, as observed in LBCS
      offspring, are indictors of increased diabetes risk in humans. These findings
      suggest that altered maternal body composition and an imbalance between the fetal
      and postnatal environment influence offspring glucose tolerance.

PMID- 18332238
TI  - Safety of antiplatelet therapy prior to intravenous thrombolysis in acute
      ischemic stroke.
AB  - BACKGROUND: There is some uncertainty whether prior use of antiplatelet (AP)
      drugs increases the risk of symptomatic intracerebral hemorrhage (SICH) and
      influences functional outcome in patients with ischemic stroke treated with
      intravenous thrombolysis. OBJECTIVE: To assess whether prior use of AP drugs is
      related to outcome following intravenous tissue plasminogen activator therapy in
      patients with ischemic stroke. DESIGN, SETTING, AND PATIENTS: A single-center
      prospective observational cohort study of the relation between prior AP therapy,
      occurrence of SICH, and functional outcome of consecutive patients with ischemic
      stroke undergoing intravenous thrombolysis with tissue plasminogen activator in a
      university hospital between April 1, 2002, and November 30, 2006. MAIN OUTCOME
      MEASURES: The occurrence of SICH and favorable outcome reflecting independence
      defined as a modified Rankin Scale score of 2 or lower at 3 months. RESULTS: Of
      the 301 patients who received intravenous tissue plasminogen activator, 89 used
      AP drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in
      12 patients (13.5%; 95% confidence interval, 7.8%-22.3%) who had received AP
      drugs and in 6 patients (2.8%; 95% confidence interval, 1.2%-6.2%) without prior
      AP therapy (P = .001). Multivariate analysis revealed that prior AP therapy was
      an independent predictor of SICH (odds ratio, 6.0; 95% confidence interval, 2.0
      17.1). Nonetheless, prior AP therapy was independently associated with a
      favorable outcome (odds ratio, 2.0; 95% confidence interval, 1.0-4.3).
      CONCLUSION: Despite a higher incidence of SICH, the net benefit of intravenous
      tissue plasminogen activator therapy for acute ischemic stroke was greater in
      patients using AP drugs.

PMID- 18332239
TI  - Neuromics.

PMID- 18332240
TI  - Neuromics and neurological disease.

PMID- 18332242
TI  - Stem cells on the brain.

PMID- 18332243
TI  - The HapMap: charting a course for genetic discovery in neurological diseases.
AB  - Whole-genome association analyses have begun to yield confirmed findings for
      genetic risk variants for complex disease. As the first reports of its
      application to neurological disease are described, we review this progress,
      explain the principles of the analysis, and discuss what the future is likely to
      be in this exciting area.

PMID- 18332244
TI  - Retromer sorting: a pathogenic pathway in late-onset Alzheimer disease.
AB  - During the tail end of the 20th century, a "golden period" in Alzheimer disease
      (AD) research, many of the pathogenic molecules of the autosomal dominant form of
      the disease were isolated. These molecular defects, however, do not exist in
      "sporadic" late-onset AD, the form of the disease that accounts for more than 95%
      of all cases. Pinpointing the pathogenic molecules of late-onset AD has,
      therefore, become an urgent goal, both for understanding disease mechanisms and
      for opening up novel therapeutic avenues. The retromer sorting pathway transports
      cargo along the endosome-trans-Golgi network, and retromer defects were first
      implicated in late-onset AD by a study that combined brain imaging with
      microarray. A range of studies have confirmed that defects in this pathway can
      play a pathogenic role in the disease. Herein, these findings will be reviewed,
      the details of the retromer sorting pathway will be discussed, and a biological
      model that can account for the disease's regional selectivity will be elaborated.

PMID- 18332245
TI  - Genome-wide association studies in Alzheimer disease.
AB  - The genetics of Alzheimer disease (AD) to date support an age-dependent
      dichotomous model whereby earlier age of disease onset (< 60 years) is explained
      by 3 fully penetrant genes (APP [NCBI Entrez gene 351], PSEN1 [NCBI Entrez gene
      5663], and PSEN2 [NCBI Entrez gene 5664]), whereas later age of disease onset (>
      or = 65 years) representing most cases of AD has yet to be explained by a purely
      genetic model. The APOE gene (NCBI Entrez gene 348) is the strongest genetic risk
      factor for later onset, although it is neither sufficient nor necessary to
      explain all occurrences of disease. Numerous putative genetic risk alleles and
      genetic variants have been reported. Although all have relevance to biological
      mechanisms that may be associated with AD pathogenesis, they await replication in
      large representative populations. Genome-wide association studies have emerged as
      an increasingly effective tool for identifying genetic contributions to complex
      diseases and represent the next frontier for furthering our understanding of the
      underlying etiologic, biological, and pathologic mechanisms associated with
      chronic complex disorders. There have already been success stories for diseases
      such as macular degeneration and diabetes mellitus. Whether this will hold true
      for a genetically complex and heterogeneous disease such as AD is not known,
      although early reports are encouraging. This review considers recent publications
      from studies that have successfully applied genome-wide association methods to
      investigations of AD by taking advantage of the currently available high
      throughput arrays, bioinformatics, and software advances. The inherent strengths,
      limitations, and challenges associated with study design issues in the context of
      AD are presented herein.

PMID- 18332246
TI  - Maternal transmission of multiple sclerosis in a dutch population.
AB  - OBJECTIVE: To investigate the parental relationship of patients with multiple
      sclerosis (MS) from an extended pedigree with extensive genealogical information
      up to the middle of the 18th century. DESIGN: Multiple sclerosis is a complex
      disease resulting from genetic and environmental factors. Parent-of-origin
      effect, a phenomenon when the same allele may express differently depending on
      the sex of the transmitting parent, may influence the risk for MS. We
      investigated parental relationships between patients with MS using extensive
      genealogical information available from the Genetic Research in Isolated
      Populations program. We compared the average kinship of the parents of MS
      patients. We further explored the distribution of shortest genealogical links
      between parents of MS patients. Subjects Twenty-four MS patients from the
      isolated population who could be linked within a large complex pedigree,
      including 2471 people in total. RESULTS: The results consistently indicate a
      higher prevalence of maternal transmission of MS. The kinship between mothers of
      patients was 3.8 times higher than that between fathers (bootstrap P = .01).
      Among the 814 shortest connections between parents, 333 were maternal (40.9%, vs
      25.0% expected), 98 were paternal (12.0%, vs 25.0% expected), and 383 were
      maternal-paternal (47.1%, vs 50.0% expected) (P < .001). CONCLUSIONS: Mothers of
      MS patients were more closely related than their fathers. This skewed
      relationship shows evidence for a maternal effect in MS. The most likely
      explanation is a gene-environment effect that takes place in utero.

PMID- 18332247
TI  - Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility
      and gene expression.
AB  - BACKGROUND: Interferon (IFN) gamma (IFNG) allelic variants are associated with
      susceptibility to multiple sclerosis (MS) in men but not in women. OBJECTIVES: To
      conduct a high-density linkage disequilibrium association study of IFNG and the
      surrounding region for sex-associated MS susceptibility bias and to evaluate
      whether IFNG allelic variants associated with MS susceptibility are associated
      with expression. DESIGN: Genotype case-control study, quantitative polymerase
      chain reaction (qPCR), and enzyme-linked immunosorbent assay expression analyses
      for IFN gamma. SETTING: Three independently ascertained populations from the Mayo
      Clinic, Rochester, Minnesota, Queen's University of Belfast, Belfast, Ireland,
      and University of Leuven, Leuven, Belgium. PATIENTS: For linkage disequilibrium,
      861 patients with MS (293 men and 568 women) and 843 controls (340 men and 503
      women) derived from the US (population-based) and the Northern Ireland and
      Belgium (clinic-based) cohorts were studied. For expression analyses, 50 US
      patients were selected to enrich for homozygotes and to achieve a balance between
      men and women. INTERVENTIONS: Twenty markers were genotyped over the 120-kilobase
      region harboring IFNG and the interleukin 26 gene (IL26). MAIN OUTCOME MEASURES:
      Expression of IFN gamma was evaluated by qPCR and enzyme-linked immunosorbent
      assay in stimulated peripheral blood mononuclear cells. RESULTS: Multiple markers
      were associated with MS susceptibility in men but not in women. The sex-specific
      susceptibility markers, of which rs2069727 was the strongest, were confined to
      IFNG. Carriers of rs2069727*G had higher expression than noncarriers. The effect
      of genotype in the qPCR experiments was also evident in men but not in women.
      CONCLUSIONS: IFNG is associated with sex bias in MS susceptibility and with
      expression of IFN gamma in MS. These observations add to a growing body of
      literature that implicates an interaction between sex and IFN gamma expression in
      a variety of disease states.

PMID- 18332248
TI  - Cortical brain malformations: effect of clinical, neuroradiological, and modern
      genetic classification.
AB  - BACKGROUND: Malformations of cortical development (MCDs) are a major source of
      handicap. Much progress in understanding the genetic causes has been made
      recently. The number of affected children in whom a molecularly confirmed
      diagnosis can be made is unclear. OBJECTIVE: To evaluate the etiology of MCDs in
      children and the effect of a combined radiological, clinical, and syndrome
      classification. DESIGN: A case series of 113 children with a radiological
      diagnosis of MCD from January 1, 1992, to January 1, 2006. SETTING: The Erasmus
      Medical Center-Sophia Children's Hospital, a secondary and tertiary referral
      center. PATIENTS: Patients with MCD underwent a complete radiological, clinical,
      and neurological assessment and testing for known genes involved in the
      pathogenesis of MCD as appropriate for their phenotype. RESULTS: We established
      an etiological diagnosis in 45 of 113 cases (40%). For 21 patients (19%), this
      included molecular and/or genetic confirmation (Miller-Dieker syndrome; LIS1,
      DCX, FLNA, EIF2AK3, or KIAA1279 mutations; or an inborn error of metabolism). In
      17 (15%), a syndrome with an unknown genetic defect was diagnosed. In 7 patients
      (6%), we found evidence of a gestational insult. Of the remaining 68 patients, 34
      probably have a yet-unknown genetic disorder based on the presence of multiple
      congenital anomalies (15 patients), a family history with multiple affected
      persons (12 patients), or consanguineous parents (7 patients). CONCLUSIONS: In
      our cohort, combining diagnostic molecular testing with clinical, radiological,
      and genetic classification; syndrome identification; and family study provided a
      diagnosis in 40% of the cases of MCD. This contributes to the possibility of
      prenatal diagnosis and improved patient treatment and disease management.

PMID- 18332249
TI  - The G13513A mutation in the ND5 gene of mitochondrial DNA as a common cause of
      MELAS or Leigh syndrome: evidence from 12 cases.
AB  - BACKGROUND: The number of molecular causes of MELAS (a syndrome consisting of
      mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) and
      Leigh syndrome (LS) has steadily increased. Among these, mutations in the ND5
      gene (OMIM 516005) of mitochondrial DNA are important, and the A13513A change has
      emerged as a hotspot. OBJECTIVE: To describe the clinical features, muscle
      pathological and biochemical characteristics, and molecular study findings of 12
      patients harboring the G13513A mutation in the ND5 gene of mitochondrial DNA
      compared with 14 previously described patients with the same mutation. DESIGN:
      Clinical examinations and morphological, biochemical, and molecular analyses.
      SETTING: Tertiary care university hospital and molecular diagnostic laboratory.
      PATIENTS: Three patients had the typical syndrome features of MELAS; the other 9
      had typical clinical and radiological features of LS. RESULTS: Family history
      suggested maternal inheritance in a few cases; morphological studies of muscle
      samples rarely showed typical ragged-red fibers and more often exhibited strongly
      succinate dehydrogenase-reactive blood vessels. Biochemically, complex I
      deficiency was inconsistent and generally mild. The mutation load was relatively
      high in the muscle and blood specimens. CONCLUSION: The G13513A mutation is a
      common cause of MELAS and LS, even in the absence of obvious maternal
      inheritance, pathological findings in muscle, or severe complex I deficiency.

PMID- 18332250
TI  - Conjugal Alzheimer disease: risk in children when both parents have Alzheimer
      disease.
AB  - BACKGROUND: There is limited information regarding children's risk of Alzheimer
      disease (AD) if both parents are affected. OBJECTIVE: To determine the risk of AD
      in families in which both parents have AD. DESIGN: Retrospective study. SETTING:
      University research center. PARTICIPANTS: A total of 111 families in which both
      parents had a clinical diagnosis of AD. Main Outcome Measure Frequency of AD in
      the children of spouses with AD. RESULTS: The 111 couples with AD had 297
      children surviving to adulthood; 22.6% of these adult children have developed AD.
      The risk of AD in these children increases with age, being 31.0% (58 of 187) in
      those older than 60 years and 41.8% (41 of 98) in those older than 70 years. Many
      children (79.0%) at risk in these families are still younger than 70 years,
      meaning that the occurrence of AD will increase in the coming years. A family
      history of AD beyond the parents did not change the risk of AD in the children
      but did reduce the median age at onset in affected children. The apolipoprotein E
      epsilon4 allele played an important part in this phenomenon but did not explain
      all cases of AD in the children. CONCLUSIONS: When both parents have AD, there is
      an increased risk of AD in their children beyond that of the general population.
      The role of family history and the specific genes involved in this phenomenon
      require a better definition.

PMID- 18332251
TI  - Glucocerebrosidase gene mutations: a risk factor for Lewy body disorders.
AB  - BACKGROUND: Mutations in the glucocerebrosidase (GBA) gene have been reported to
      modify risk for Parkinson disease (PD) and dementia with Lewy bodies (DLB).
      However, these findings have not been consistently replicated, and most studies
      have had substantial methodological shortcomings. OBJECTIVE: To better assess the
      role of GBA variants in altering risk for Lewy body disorders. DESIGN: Case
      control study. SETTING: Four movement disorder clinics in the Seattle,
      Washington, area. PARTICIPANTS: Seven hundred twenty-one patients with PD, 554
      healthy control subjects, and 57 patients with DLB. MAIN OUTCOME MEASURES:
      Disease status and presence or absence of the 2 most common GBA mutations (N370S
      and L444P). RESULTS: We observed a significantly higher heterozygote frequency
      for the 2 mutations in patients with PD (2.9%; P <.001) and those with DLB (3.5%;
      P = .045) compared with control subjects (0.4%). CONCLUSION: Our findings suggest
      that GBA mutations exert a large effect on susceptibility for Lewy body disorders
      at the individual level but are associated with a modest (approximately 3%)
      population-attributable risk in individuals of European ancestry.

PMID- 18332252
TI  - A locus for primary lateral sclerosis on chromosome 4ptel-4p16.1.
AB  - BACKGROUND: Primary lateral sclerosis (PLS) is an adult-onset upper motor neuron
      disease resulting in spinal and bulbar spasticity. A family with 8 individuals
      diagnosed with PLS was previously reported. OBJECTIVE: To identify a locus for a
      large family with PLS. METHODS: A 550-marker whole-genome scan was performed on
      this family followed by fine mapping with sequence-tagged site markers to
      identify a candidate region. RESULTS: A locus was identified for this family
      between the telomere of chromosome 4 and marker D4S2928 (4ptel-4p16.1). A maximum
      lod score of 3.01 was obtained for marker D4S2936. The region spans 23.17 cM
      (10.2 megabase pairs) and encompasses 130 genes. CONCLUSIONS: PLS1 does not map
      near any other identified loci for upper or lower motor neuron diseases and thus
      represents a novel locus for PLS.

PMID- 18332253
TI  - Long-term follow-up of Taiwanese Chinese patients treated early for 6-pyruvoyl
      tetrahydropterin synthase deficiency.
AB  - OBJECTIVE: To report the long-term results of early initiation of treatment of 6
      pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. DESIGN: Between 1988 and
      2000, 12 newborns with PTPS deficiency who underwent early treatment at our
      hospital were identified. All patients received tetrahydrobiopterin replacement
      in a daily dosage between approximately 2 and 4 mg/kg. The dosages of levodopa
      replacement were 10 to 15 mg/kg/d, which is considerably higher than the
      typically recommended dosages of less than 7 mg/kg/d for patients aged younger
      than 2 years and 8 to 10 mg/kg/d for patients aged 2 years or older. Replacement
      with 5-hydroxytryptophan varied widely among patients. SETTING: Taipei Veterans
      General Hospital. Patients Twelve newborns. INTERVENTIONS: Treatment with
      tetrahydrobiopterin, levodopa, and 5-hydroxytryptophan. Main Outcome Measure IQ
      score. RESULTS: The mean (SD) IQ score of our PTPS-deficient patients was 96.7
      (9.7; range 86-119), which is considerably higher than previous reports of other
      populations of PTPS-deficient patients. All patients reached a normal IQ on high
      daily dosages of levodopa replacement, without developing apparent long-term
      levodopa-induced adverse effects. We also observed a correlation between long
      term IQ score and genotype, birth weight, and age at initiation of treatment.
      CONCLUSIONS: An effective newborn screening referral program and early initiation
      of appropriate therapy preserved the IQ scores of PTPS-deficient patients.

PMID- 18332254
TI  - Hereditary spastic paraplegia with mental impairment and thin corpus callosum in
      Tunisia: SPG11, SPG15, and further genetic heterogeneity.
AB  - OBJECTIVE: To perform a clinical and genetic study of Tunisian families with
      autosomal recessive (AR) hereditary spastic paraplegia with thin corpus callosum
      (HSP-TCC). DESIGN: Linkage studies and mutation screening. SETTING: Reference
      Center for Neurogenetics in South and Center Tunisia. PARTICIPANTS: Seventy-three
      subjects from 33 "apparently" unrelated Tunisian families with AR HSP. MAIN
      OUTCOME MEASURES: Families with AR HSP-TCC were subsequently tested for linkage
      to the corresponding loci using microsatellite markers from the candidate
      intervals, followed by direct sequencing of the KIAA1840 gene in families linked
      to SPG11. RESULTS: We identified 8 Tunisian families (8 of 33 [24%]), including
      19 affected patients, fulfilling the clinical criteria for HSP-TCC. In 7
      families, linkage to either SPG11 (62.5%) or SPG15 (25%) was suggested by
      haplotype reconstruction and positive logarithm of odds score values for
      microsatellite markers. The identification of 2 recurrent mutations (R2034X and
      M245VfsX) in the SPG11 gene in 5 families validated the linkage results. The
      neurological and radiological findings in SPG11 and SPG15 patients were
      relatively similar. The remaining family, characterized by an earlier age at
      onset and the presence of cataracts, was excluded for linkage to the 6 known
      loci, suggesting further genetic heterogeneity. CONCLUSIONS: Autosomal recessive
      HSP-TCC is a frequent subtype of complicated HSP in Tunisia and is clinically and
      genetically heterogeneous. SPG11 and SPG15 are the major loci for this entity,
      but at least another genetic form with unique clinical features exists.

PMID- 18332255
TI  - Amyotrophic lateral sclerosis with ragged-red fibers.
AB  - BACKGROUND: Motor neuron diseases (amyotrophic lateral sclerosis [ALS] and spinal
      muscular atrophy [SMA]) have been rarely associated with mitochondrial
      respiratory chain defects. OBJECTIVES: To describe a patient with typical ALS and
      the finding of ragged-red fibers in muscle biopsy specimens and to review the
      literature on respiratory chain defects in ALS and SMA. DESIGN: Case report and
      review of the literature. SETTING: Collaboration between tertiary care academic
      hospitals. PATIENT: A 65-year-old man with typical ALS. MAIN OUTCOME MEASURES:
      The patient had 10% ragged-red fibers and 3% cytochrome-c oxidase-negative fibers
      in muscle biopsy specimens but no biochemical defects of respiratory chain
      enzymes or alterations of mitochondrial DNA (mtDNA). RESULTS: Amyotrophic lateral
      sclerosis with ragged-red fibers has been reported in 5 families and is
      associated with mtDNA mutations in some subjects. Spinal muscular atrophy without
      mutations in the survival motor neuron gene (SMN; OMIM 600354) has been
      associated with mtDNA depletion or with mutations in the cytochrome-c oxidase
      assembly gene (SCO2; OMIM 604377). CONCLUSION: Respiratory chain defects can
      mimic ALS or SMA and should be considered in the differential diagnosis.

PMID- 18332256
TI  - Altered cerebral glucose metabolism in a family with clinical features resembling
      mitochondrial neurogastrointestinal encephalomyopathy syndrome in association
      with multiple mitochondrial DNA deletions.
AB  - OBJECTIVE: To determine the involvement of cerebral metabolism in 2 siblings with
      mitochondrial neurogastrointestinal encephalomyopathy syndrome (MNGIE)-like
      disease with multiple mitochondrial DNA (mtDNA) deletions. DESIGN: Case report.
      SETTING: Department of Neurology at a university medical center. PATIENTS: Two
      siblings with MNGIE-like disease with multiple mtDNA deletions. MAIN OUTCOME
      MEASURES: Clinical, biochemical, genetic, and imaging findings, including
      cerebral magnetic resonance imaging, proton magnetic resonance spectroscopy, and
      positron emission tomography with fluorine 18-labeled deoxyglucose (FDG-PET).
      RESULTS: Genetic analysis of muscle DNA revealed multiple mtDNA deletions, while
      no mutations were detected in ECGF1, POLG1, ANT1, or Twinkle. Cerebral magnetic
      resonance imaging and proton magnetic resonance spectroscopy findings were
      unremarkable. Reduced regional glucose metabolism was found in a patchy and
      asymmetrical pattern predominantly in the frontotemporal region in both siblings
      by means of FDG-PET. CONCLUSIONS: The discrepancy between absence of clinical
      signs of cerebral involvement and the substantial impairment of glucose
      metabolism reflects a chronic subclinical encephalopathy. To our knowledge, the
      predominantly frontotemporal distribution has not been described previously in
      mitochondrial disorders.

PMID- 18332257
TI  - Mosaicism for trisomy 21 in a patient with young-onset dementia: a case report
      and brief literature review.
AB  - OBJECTIVE: To describe a case of young-onset Alzheimer disease (AD) due to
      mosaicism for trisomy 21. DESIGN: Case report of a single patient. SETTING:
      Tertiary referral dementia clinic. PATIENT: A 55-year-old man with a mild degree
      of developmental delay but no previous diagnosis of Down syndrome and only
      minimal physical manifestations of Down syndrome presented with gradually
      progressive cognitive impairment consistent with probable AD. RESULTS:
      Fluorescent in situ hybridization analysis of interphase chromosomes revealed
      trisomy 21 in 10% of peripheral lymphocytes. CONCLUSIONS: As mosaicism for
      trisomy 21 can present with no or minimal manifestations of Down syndrome, it may
      be underdiagnosed as a cause of early-onset AD. Occult mosaicism for trisomy 21
      may explain in part the previously described association between family history
      of Down syndrome and risk of AD. Screening for mosaicism with fluorescent in situ
      hybridization is indicated in selected patients with mild developmental delay and
      those with AD of young onset.

PMID- 18332258
TI  - Rapid exacerbation in an elderly case of adult-onset X-linked
      adrenoleukodystrophy with cerebral corticospinal tract involvement.

PMID- 18332259
TI  - The consciousness dilemma: feel or feel of feeling?

PMID- 18332260
TI  - Migraine Intervention With STARFlex Technology trial: a controversial trial of
      migraine and patent foramen ovale closure.

PMID- 18332261
TI  - Hemodynamic effects of volume expansion in patients with cardiac tamponade.
AB  - BACKGROUND: Volume expansion has been proposed as an alternative treatment for
      cardiac tamponade; however, the scientific evidence for this recommendation is
      very poor. METHODS AND RESULTS: Forty-nine unselected patients (23 males; age
      55+/-16 years) with large pericardial effusion and hemodynamic tamponade
      underwent fluid overload with intravenous administration of 500 mL of normal
      saline over 10 minutes. Cardiac index and intrapericardial, left ventricular end
      diastolic, right atrial, and right ventricular end-diastolic pressures were
      measured during basal state (tamponade), after fluid overload, and after
      pericardiocentesis. Twenty-eight patients (57%) had physical signs of tamponade,
      and 10 (20%) were hypotensive. Size of pericardial effusion was 31+/-13 mm.
      Initial mean arterial pressure was 88+/-21 mm Hg, and cardiac index was 2.46+/
      0.80 L x min(-1) x m(-2). Intrapericardial pressure was 8.31+/-5.98 mm Hg. Volume
      expansion caused a significant increase in mean arterial pressure (from 88+/-21
      to 94+/-23 mm Hg, P=0.003) and cardiac index (from 2.46+/-0.80 to 2.64+/-0.68 L x
      min(-1) x m(-2), P=0.013), as well as in intrapericardial pressure (from 8.31+/
      5.98 to 11.02+/-6.27 mm Hg, P=0.0001), right atrial pressure (from 9.76+/-5.91 to
      12.82+/-6.34 mm Hg, P=0.0001), and left ventricular end-diastolic pressure (from
      14.21+/-5.97 to 19.48+/-6.19 mm Hg, P=0.0001). Cardiac index increased by >10% in
      23 patients (47%), remained unchanged in 11 (22%), and decreased in 15 (31%). No
      patient developed clinical complications. Predictors of this favorable response
      were systolic blood pressure <100 mm Hg and low cardiac index. CONCLUSIONS:
      Approximately one half of patients with cardiac tamponade develop a significant
      increase in cardiac output after volume overload. Low systolic blood pressure
      (<100 mm Hg) at baseline was the simplest clinical finding that was predictive of
      this favorable response.

PMID- 18332262
TI  - Survivin determines cardiac function by controlling total cardiomyocyte number.
AB  - BACKGROUND: Survivin inhibits apoptosis and regulates cell division in many
      organs, but its function in the heart is unknown. METHODS AND RESULTS: We show
      that cardiac-specific deletion of survivin resulted in premature cardiac death.
      The underlying cause was a dramatic reduction in total cardiomyocyte numbers as
      determined by a stereological method for quantification of cells per organ. The
      resulting increased hemodynamic load per cell led to progressive heart failure as
      assessed by echocardiography, magnetic resonance imaging, positron emission
      tomography, and invasive catheterization. The reduction in total cardiomyocyte
      number in alpha-myosin heavy chain (MHC)-survivin(-/-) mice was due to an
      approximately 50% lower mitotic rate without increased apoptosis. This occurred
      at the expense of DNA accumulation because survivin-deficient cardiomyocytes
      displayed marked DNA polyploidy indicative of consecutive rounds of DNA
      replication without cell division. Survivin small interfering RNA knockdown in
      neonatal rat cardiomyocytes also led to polyploidization and cell cycle arrest
      without apoptosis. Adenoviral overexpression of survivin in cardiomyocytes
      inhibited doxorubicin-induced apoptosis, induced DNA synthesis, and promoted cell
      cycle progression. The phenotype of the alphaMHC-survivin(-/-) mice also allowed
      us to determine the minimum cardiomyocyte number sufficient for normal cardiac
      function. In human cardiomyopathy, survivin was potently induced in the failing
      heart and downregulated again after hemodynamic support by a left ventricular
      assist device. Its expression positively correlated with the mean cardiomyocyte
      DNA content. CONCLUSIONS: We suggest that the ontogenetically determined
      cardiomyocyte number may be an independent factor in the susceptibility to
      cardiac diseases. Through its profound impact on both cardiomyocyte replication
      and apoptosis, survivin may emerge as a promising new target for myocardial
      regeneration.

PMID- 18332263
TI  - Ablation of matrix metalloproteinase-9 increases severity of viral myocarditis in
      mice.
AB  - BACKGROUND: Coxsackievirus B3 (CVB3) causes human myocarditis, which can result
      in cardiac damage, maladaptive remodeling, and heart failure. Matrix
      metalloproteinases (MMP)-8 and -9 have been identified in virus-infected
      myocardium, but their particular roles and underlying mechanisms of effect are
      unknown. For the first time, we examine the severity of CVB3-induced myocarditis
      in MMP-8-and MMP-9-deficient mice. METHODS AND RESULTS: CVB3-infected MMP-8 and
      MMP-9 knockout (KO) mice and corresponding wild-type (WT) mice were euthanized
      and harvested at 9 days after infection. Expression of MMP-2, -8, -12, and -13
      and tissue inhibitors of MMPs was assessed by zymography or immunoblotting on
      harvested hearts, and in situ hybridization was performed to detect active
      infection. Infected MMP-9 KO mice had greater myocardial injury and foci of
      infection than WT mice despite similar pancreatic infection. Increased fibrosis
      (10.6+/-2.7% versus 7.1+/-2.6%, P=0.04), viral titer, as well as decreased
      cardiac output, were evident in MMP-9 KO compared with WT mice as assessed by
      picrosirius red staining, plaque assay, and echocardiography, respectively.
      Immune infiltration was also greatly increased in MMP-9 KO compared with WT mice
      (15.2+/-12.6% versus 2.0+/-3.0%, P<0.002). Myocardial interferon-beta1,
      interferon-gamma, interleukin-6, interleukin-10, and macrophage inflammatory
      protein-1alpha expression was elevated in MMP-9 KO mice as measured by
      quantitative real-time polymerase chain reaction and ELISA. In contrast, MMP-8 KO
      mice had the same degree of cardiac injury, fibrosis, and viral infection as
      their WT counterparts. CONCLUSIONS: During acute CVB3 infection, MMP-9 appears
      necessary to halt virus propagation in the heart, promote proper immune
      infiltration and remodeling, and preserve cardiac output.

PMID- 18332264
TI  - Magnetic resonance imaging overestimates ferumoxide-labeled stem cell survival
      after transplantation in the heart.
AB  - BACKGROUND: Stem cell labeling with iron oxide (ferumoxide) particles allows
      labeled cells to be detected by magnetic resonance imaging (MRI) and is commonly
      used to track stem cell engraftment. However, the validity of MRI for
      distinguishing surviving ferumoxide-labeled cells from other sources of MRI
      signal, for example, macrophages containing ferumoxides released from
      nonsurviving cells, has not been thoroughly investigated. We sought to determine
      the relationship between the persistence of iron-dependent MRI signals and cell
      survival 3 weeks after injection of syngeneic or xenogeneic ferumoxides-labeled
      stem cells (cardiac-derived stem cells) in rats. METHODS AND RESULTS: We studied
      nonimmunoprivileged human and rat cardiac-derived stem cells and human
      mesenchymal stem cells doubly labeled with ferumoxides and beta-galactosidase and
      injected intramyocardially into immunocompetent Wistar-Kyoto rats. Animals were
      imaged at 2 days and 3 weeks after stem cell injection in a clinical 3-T MRI
      scanner. At 2 days, injection sites of xenogeneic and syngeneic cells (cardiac
      derived stem cells and mesenchymal stem cells) were identified by MRI as large
      intramyocardial signal voids that persisted at 3 weeks (50% to 90% of initial
      signal). Histology (at 3 weeks) revealed the presence of iron-containing
      macrophages at the injection site, identified by CD68 staining, but very few or
      no beta-galactosidase-positive stem cells in the animals transplanted with
      syngeneic or xenogeneic cells, respectively. CONCLUSIONS: The persistence of
      significant iron-dependent MRI signal derived from ferumoxide-containing
      macrophages despite few or no viable stem cells 3 weeks after transplantation
      indicates that MRI of ferumoxide-labeled cells does not reliably report long-term
      stem cell engraftment in the heart.

PMID- 18332265
TI  - Restrictive left ventricular filling pattern does not result from increased left
      atrial pressure alone.
AB  - BACKGROUND: The restrictive filling pattern seen with severe heart failure (HF)
      may be due to diastolic dysfunction with elevated left ventricular (LV) diastolic
      pressure or may be merely a manifestation of an overfilled LV as a result of
      increased left atrial (LA) pressure. We investigated whether the LV restrictive
      filling pattern is due to elevated LA pressure alone. METHODS AND RESULTS: We
      studied conscious dogs instrumented to measure LA pressure, LV pressure, and 3 LV
      diameters. LV filling dynamics were evaluated in 2 situations with similar
      elevations of LA pressure: in normal animals after rapid volume loading with
      dextran 500 mL and in animals with pacing-induced HF with restrictive filling.
      With HF, there was increased LV chamber stiffness and slow relaxation. Volume
      loading and HF had similar heart rates (129+/-19 versus 131+/-15 bpm) and LA
      pressure (22.1+/-5.8 versus 22.6+/-3.3 mm Hg). The peak early filling rate (E)
      was increased with both HF and volume loading. However, in HF, the peak mitral
      annular velocity (E') was decreased and delayed, and the E deceleration time was
      shorter. In contrast, with volume loading, E' was increased and not delayed.
      CONCLUSIONS: The restrictive filling pattern is distinguished from overfilling of
      a normal ventricle by a reduced and delayed E' and a shortened E deceleration
      time that reflect slow relaxation and increased LV stiffness.

PMID- 18332266
TI  - Epicardium-derived cells in development of annulus fibrosis and persistence of
      accessory pathways.
AB  - BACKGROUND: The developmental mechanisms underlying the persistence of myocardial
      accessory atrioventricular pathways (APs) that bypass the annulus fibrosis are
      mainly unknown. In the present study, we investigated the role of epicardium
      derived cells (EPDCs) in annulus fibrosis formation and the occurrence of APs.
      METHODS AND RESULTS: EPDC migration was mechanically inhibited by in ovo
      microsurgery in quail embryos. In ovo ECGs were recorded in wild-type (n=12) and
      EPDC-inhibited (n=12) hearts at Hamburger-Hamilton (HH) stages 38 to 42.
      Subsequently, in these EPDC-inhibited hearts (n=12) and in additional wild-type
      hearts (n=45; HH 38-42), ex ovo extracellular electrograms were recorded.
      Electrophysiological data were correlated with differentiation markers for
      cardiomyocytes (MLC2a) and fibroblasts (periostin). In ovo ECGs showed
      significantly shorter PR intervals in EPDC-inhibited hearts (45+/-10 ms) than in
      wild-type hearts (55+/-8 ms, 95% CI 50 to 60 ms, P=0.030), whereas the QRS
      durations were significantly longer in EPDC-inhibited hearts (29+/-14 versus 19+/
      2 ms, 95% CI 18 to 21 ms, P=0.011). Furthermore, ex ovo extracellular
      electrograms (HH 38-42) displayed base-first ventricular activation in 44%
      (20/45) of wild-type hearts, whereas in all EPDC-inhibited hearts (100%, 12/12),
      the ventricular base was activated first (P<0.001). Small periostin- and MLC2a
      positive APs were found mainly in the posteroseptal region of both wild-type and
      EPDC-inhibited hearts. Interestingly, in all (n=10) EPDC-inhibited hearts,
      additional large periostin-negative and MLC2a-positive APs were found in the
      right and left lateral free wall coursing through marked isolation defects in the
      annulus fibrosis until the last stages of embryonic development. CONCLUSIONS:
      EPDCs play an important role in annulus fibrosis formation. EPDC outgrowth
      inhibition may result in marked defects in the fibrous annulus with persistence
      of large APs, which results in ventricular preexcitation on ECG. These APs may
      provide a substrate for postnatally persistent reentrant arrhythmias.

PMID- 18332267
TI  - Vernakalant hydrochloride for rapid conversion of atrial fibrillation: a phase 3,
      randomized, placebo-controlled trial.
AB  - BACKGROUND: The present study assessed the efficacy and safety of vernakalant
      hydrochloride (RSD1235), a novel compound, for the conversion of atrial
      fibrillation (AF). METHODS AND RESULTS: Patients were randomized in a 2:1 ratio
      to receive vernakalant or placebo and were stratified by AF duration of 3 hours
      to 7 days (short duration) and 8 to 45 days (long duration). A first infusion of
      placebo or vernakalant (3 mg/kg) was given for 10 minutes, followed by a second
      infusion of placebo or vernakalant (2 mg/kg) 15 minutes later if AF was not
      terminated. The primary end point was conversion of AF to sinus rhythm for at
      least 1 minute within 90 minutes of the start of drug infusion in the short
      duration AF group. A total of 336 patients were randomized and received treatment
      (short duration, n=220; long duration, n=116). Of the 145 vernakalant patients,
      75 (51.7%) in the short-duration AF group converted to sinus rhythm (median time,
      11 minutes) compared with 3 of the 75 placebo patients (4.0%; P<0.001). Overall,
      in the short- and long-duration AF groups, 83 of the 221 vernakalant patients
      (37.6%) experienced termination of AF compared with 3 of the 115 placebo patients
      (2.6%; P<0.001). Transient dysgeusia and sneezing were the most common side
      effects in vernakalant-treated patients. Four vernakalant-related serious adverse
      events (hypotension [2 events], complete atrioventricular block, and cardiogenic
      shock) occurred in 3 patients. CONCLUSIONS: Vernakalant demonstrated rapid
      conversion of short-duration AF and was well tolerated.

PMID- 18332268
TI  - Human apolipoprotein A-I gene transfer reduces the development of experimental
      diabetic cardiomyopathy.
AB  - BACKGROUND: The hallmarks of diabetic cardiomyopathy are cardiac oxidative
      stress, intramyocardial inflammation, cardiac fibrosis, and cardiac apoptosis.
      Given the antioxidative, antiinflammatory, and antiapoptotic potential of high
      density lipoprotein (HDL), we evaluated the hypothesis that increased HDL via
      gene transfer (GT) with human apolipoprotein (apo) A-I, the principal
      apolipoprotein of HDL, may reduce the development of diabetic cardiomyopathy.
      METHODS AND RESULTS: Intravenous GT with 3x10(12) particles/kg of the E1E3E4
      deleted vector Ad.hapoA-I, expressing human apoA-I, or Ad.Null, containing no
      expression cassette, was performed 5 days after streptozotocin (STZ) injection.
      Six weeks after apoA-I GT, HDL cholesterol levels were increased by 1.6-fold
      (P<0.001) compared with diabetic controls injected with the Ad.Null vector (STZ
      Ad.Null). ApoA-I GT and HDL improved LV contractility in vivo and cardiomyocyte
      contractility ex vivo, respectively. Moreover, apoA-I GT was associated with
      decreased cardiac oxidative stress and reduced intramyocardial inflammation. In
      addition, compared with STZ-Ad.Null rats, cardiac fibrosis and glycogen
      accumulation were reduced by 1.7-fold and 3.1-fold, respectively (P<0.05).
      Caspase 3/7 activity was decreased 1.2-fold (P<0.05), and the ratio of Bcl-2 to
      Bax was upregulated 1.9-fold (P<0.005), translating to 2.1-fold (P<0.05) reduced
      total number of cardiomyocytes with apoptotic characteristics and 3.0-fold
      (P<0.005) reduced damaged endothelial cells compared with STZ-Ad.Null rats. HDL
      supplementation ex vivo reduced hyperglycemia-induced cardiomyocyte apoptosis by
      3.4-fold (P<0.005). The apoA-I GT-mediated protection was associated with a 1.6-,
      1.6-, and 2.4-fold induction of diabetes-downregulated phospho to Akt,
      endothelial nitric oxide synthase, and glycogen synthase kinase ratio,
      respectively (P<0.005). CONCLUSIONS: ApoA-I GT reduced the development of
      streptozotocin-induced diabetic cardiomyopathy.

PMID- 18332269
TI  - Variation in the 3-hydroxyl-3-methylglutaryl coenzyme a reductase gene is
      associated with racial differences in low-density lipoprotein cholesterol
      response to simvastatin treatment.
AB  - BACKGROUND: Use of 3-hydroxyl-3-methylglutaryl-3 coenzyme A reductase (HMGCR)
      inhibitors, or statins, reduces cardiovascular disease risk by lowering plasma
      low-density lipoprotein cholesterol (LDL-C) concentrations. However, LDL-C
      response is variable and influenced by many factors, including racial ancestry,
      with attenuated response in blacks compared with whites. We hypothesized that
      single nucleotide polymorphisms in the gene encoding HMGCR, a rate-limiting
      enzyme in cholesterol synthesis and the direct enzymatic target of statins,
      contribute to variation in statin response. METHODS AND RESULTS: Genomic
      resequencing of HMGCR in 24 blacks and 23 whites identified 79 single nucleotide
      polymorphisms. Eleven single nucleotide polymorphisms were selected to tag common
      linkage disequilibrium clusters. These single nucleotide polymorphisms and the
      common haplotypes inferred from them were tested for association with plasma LDL
      C and LDL-C response to simvastatin treatment (40 mg/d for 6 weeks) in 326 blacks
      and 596 whites. Black carriers of H7 and/or H2 had significantly lower baseline
      LDL-C (P=0.0006) and significantly attenuated LDL-C response compared with black
      participants who did not carry either haplotype as measured by absolute response
      (-1.23+/-0.04 mmol/L, n=209, versus -1.45+/-0.06 mmol/L, n=117; P=0.0008) and
      percent response (-36.9+/-1.0% versus -40.6+/-1.3%; P=0.02), but no haplotype
      effect was observed in whites. Percent LDL-C response was lowest in carriers of
      both H2 and H7, all but one of whom were black (-28.2+/-4.9%, n=12 H2+H7
      carriers, versus -41.5+/-0.5%, n=650 H2/H7 noncarriers; P=0.001). LDL-C responses
      in H7 and/or H2 noncarriers were indistinguishable between blacks and whites.
      CONCLUSIONS: HMGCR gene polymorphisms are associated with reduced plasma LDL-C
      and LDL-C response to simvastatin, and these effects are most evident in blacks.

PMID- 18332270
TI  - Percutaneous and minimally invasive valve procedures: a scientific statement from
      the American Heart Association Council on Cardiovascular Surgery and Anesthesia,
      Council on Clinical Cardiology, Functional Genomics and Translational Biology
      Interdisciplinary Working Group, and Quality of Care and Outcomes Research
      Interdisciplinary Working Group.
AB  - The incidence of valvular heart disease is expected to increase over the next
      several decades as a large proportion of the US demographic advances into the
      later decades of life. At the same time, the next several years can be
      anticipated to bring a broad transition of surgical therapy to minimally invasive
      (minithoracotomy and small port) access and the more gradual introduction of
      percutaneous approaches for the correction of valvular heart disease. Broad
      acceptance of these technologies will require careful and sometimes perplexing
      comparisons of the outcomes of these new technologies with existing standards of
      care. The validation of percutaneous techniques, in particular, will require the
      collaboration of cardiologists and cardiac surgeons in centers with excellent
      surgical and catheter experience and a commitment to trial participation. For the
      near term, percutaneous techniques will likely remain investigational and will be
      limited in use to patients considered to be high risk or to inoperable surgical
      candidates. Although current-generation devices and techniques require
      significant modification before widespread clinical use can be adopted, it must
      be expected that less invasive and even percutaneous valve therapies will likely
      have a major impact on the management of patients with valvular heart disease
      over the next several years.

PMID- 18332271
TI  - Images in cardiovascular medicine. Unusual complication with transcatheter
      closure of an atrial septal defect prevented by adequate imaging.

PMID- 18332272
TI  - Letter by Thum et al regarding article, "Oxidant stress impairs in vivo
      reendothelialization capacity of endothelial progenitor cells from patients with
      type 2 diabetes mellitus: restoration by the peroxisome proliferator-activated
      receptor-gamma agonist rosiglitazone".

PMID- 18332273
TI  - Letter by Bollati et al regarding article, "Off-pump versus on-pump coronary
      artery bypass graft surgery: differences in short-term outcomes and in long-term
      mortality and need for subsequent revascularization".

PMID- 18332275
TI  - Atrial fibrillation susceptibility in metabolic syndrome: simply the sum of its
      parts?

PMID- 18332276
TI  - Strategies to improve medication compliance by Medicare beneficiaries.

PMID- 18332277
TI  - Screening high-risk patients with computed tomography angiography.

PMID- 18332278
TI  - All high-risk patients should not be screened with computed tomographic
      angiography.

PMID- 18332279
TI  - Pathophysiology of congenital heart disease in the adult: part III: Complex
      congenital heart disease.

PMID- 18332280
TI  - Images in cardiovascular medicine. Accessory left atrial appendage: a neglected
      anomaly and potential cause of embolic stroke.

PMID- 18332281
TI  - Older patients need better guidelines for optimal treatment of high blood
      pressure: 1 size fits few.

PMID- 18332282
TI  - Review of hypertension in Sub-Saharan Africa: a comment from the Seychelles.

PMID- 18332283
TI  - Pediatric antihypertensive trial failures: analysis of end points and dose range.
AB  - Historically, drugs prescribed for children have not been studied in pediatric
      populations. Since 1997, however, a 6-month extension of marketing rights is
      granted if manufacturers conduct Food and Drug Administration-defined pediatric
      trials. In nearly half of the drugs studied, there were unexpected results in
      dosing, safety, or efficacy compared with adult studies, including failure of
      half of the antihypertensive dose-response trials, which are pivotal for deriving
      dosing recommendations. We sought to define design elements that might have
      contributed to these trial failures by combining patient-level data from 6 dose
      ranging antihypertensive efficacy trials completed for pediatric exclusivity and
      submitted to the Food and Drug Administration from 1998 to 2005. We evaluated
      dosing, primary end point, and other components to assess underlying reasons for
      failure to show efficacy in children. Of 6 trials examined, 3 showed a dose
      response; 3 did not. Eligibility criteria were similar across studies, as were
      subject demographics. Successful studies showed large differences in doses, with
      little or no overlap between low, medium, and high doses; failed trials used
      narrow dose ranges with considerable overlap. Successful trials also provided
      pediatric formulations and used reduction in diastolic, not systolic, blood
      pressure as the primary end point. Careful attention to pediatric pharmacology
      and selection of primary end points can improve trial performance. We found poor
      dose selection, lack of acknowledgement of differences between adult and
      pediatric populations, and lack of pediatric formulations to be associated with
      failures. More importantly, our ability to combine data across trials allowed us
      to evaluate and potentially improve trial design.

PMID- 18332284
TI  - Association between thrombotic microangiopathy and reduced ADAMTS13 activity in
      malignant hypertension.
AB  - The thrombotic microangiopathy observed in malignant hypertension is similar to
      that of thrombotic thrombocytopenic purpura, which is associated with a
      deficiency of ADAMTS13, a von Willebrand factor (VWF)-cleaving protease that
      cleaves large prothrombogenic multimers. We hypothesized that ADAMTS13 is
      deficient in malignant hypertension and that the severity of thrombotic
      microangiopathy is associated with decreased ADAMTS13 activity. We included 20
      patients with malignant and 20 patients with severe hypertension, and 20 matched
      normotensive individuals served as control subjects. VWF, active VWF, and free
      hemoglobin were assessed to explore predictors of ADAMTS13 activity. Patients
      with malignant hypertension had lower ADAMTS13 activity (80%; interquartile
      range: 53% to 130%) compared with control subjects (99% interquartile range: 82%
      to 129%; P<0.01) but not compared with patients with severe hypertension
      (P=0.14). ADAMTS13 activity negatively correlated with lactic dehydrogenase
      levels after logarithmic transformation (r=-0.65; P<0.001) and was associated
      with platelet count (r=0.34; P=0.04) and the presence of schistocytes (r=-0.37;
      P=0.02). Apart from the association with thrombotic microangiopathy, ADAMTS13 was
      inversely associated with creatinine (r=-0.42; P=0.008). Increasing levels of VWF
      were associated with a decrease in ADAMTS13 activity (r=-0.34; P=0.03). There was
      no significant association between ADAMTS13 activity and other parameters,
      including blood pressure. In conclusion, ADAMTS13 is decreased in malignant
      hypertension and associated with the severity of thrombotic microangiopathy,
      likely because of the release of VWF after endothelium stimulation. A severe
      deficiency could not be demonstrated. More studies are needed to identify the
      role of ADAMTS13 in the thrombotic microangiopathy and ischemic complications of
      malignant hypertension.

PMID- 18332285
TI  - Novel use of Kaplan-Meier methods to explain age and gender differences in
      hypertension control rates.
AB  - Despite 40 years of research demonstrating the efficacy of antihypertensive
      medications for lowering blood pressure and decreasing cardiovascular disease,
      hypertension control rates worldwide remain low. We explored here how both
      medication efficacy rates and patient/physician decision-making (discontinuation
      rates) affect overall hypertension control rates. To do this we introduced the
      use of Kaplan-Meier methodology to predict hypertension control rates separately
      within age strata. An important aspect of our analysis is the use of a "treatment
      intensity score," including both the number of agent(s) and the percentage of
      maximal dose of agent(s). We investigated how blood pressure control rates vary
      with age, gender, and treatment intensity. Our analysis found that both efficacy
      and discontinuation rates at different treatment intensities vary with age and
      gender, so that for each increase in age by 1 decade, the log hazard of achieving
      controlled blood pressure at any given intensity decreases by 0.10 in men and
      0.20 in women. Overall hypertension control rates ranged from 80.8% for persons
      age 15 to 39 years to only 42.1% for persons age >/=80 years. Our analysis more
      accurately represents achievable hypertension control rates, with differences by
      gender, than previous work, because we investigated the contributions of efficacy
      and treatment aggressiveness in the control of hypertension.

PMID- 18332286
TI  - Kidney in hypertension: guyton redux.

PMID- 18332287
TI  - Women in leadership positions in the medical academic enterprise: what are the
      next steps?

PMID- 18332288
TI  - Development and validation of an all-cause mortality risk score in type 2
      diabetes.
AB  - BACKGROUND: Diabetes reduces life expectancy by 10 to 12 years, but whether death
      can be predicted in type 2 diabetes mellitus remains uncertain. METHODS: A
      prospective cohort of 7583 type 2 diabetic patients enrolled since 1995 were
      censored on July 30, 2005, or after 6 years of follow-up, whichever came first. A
      restricted cubic spline model was used to check data linearity and to develop
      linear-transforming formulas. Data were randomly assigned to a training data set
      and to a test data set. A Cox model was used to develop risk scores in the test
      data set. Calibration and discrimination were assessed in the test data set.
      RESULTS: A total of 619 patients died during a median follow-up period of 5.51
      years, resulting in a mortality rate of 18.69 per 1000 person-years. Age, sex,
      peripheral arterial disease, cancer history, insulin use, blood hemoglobin
      levels, linear-transformed body mass index, random spot urinary albumin
      creatinine ratio, and estimated glomerular filtration rate at enrollment were
      predictors of all-cause death. A risk score for all-cause mortality was developed
      using these predictors. The predicted and observed death rates in the test data
      set were similar (P > .70). The area under the receiver operating characteristic
      curve was 0.85 for 5 years of follow-up. Using the risk score in ranking cause
      specific deaths, the area under the receiver operating characteristic curve was
      0.95 for genitourinary death, 0.85 for circulatory death, 0.85 for respiratory
      death, and 0.71 for neoplasm death. CONCLUSIONS: Death in type 2 diabetes
      mellitus can be predicted using a risk score consisting of commonly measured
      clinical and biochemical variables. Further validation is needed before clinical
      use.

PMID- 18332289
TI  - Magnesium, calcium, potassium, and sodium intakes and risk of stroke in male
      smokers.
AB  - BACKGROUND: A high intake of magnesium, calcium, and potassium and a low intake
      of sodium have been hypothesized to reduce the risk of stroke. However,
      prospective data relating intake of these minerals to risk of stroke are
      inconsistent. METHODS: We examined the relationship of dietary magnesium,
      calcium, potassium, and sodium intake with risk of stroke in a cohort of 26 556
      Finnish male smokers, aged 50 to 69 years, who were free from stroke at baseline.
      Dietary intake was assessed at baseline using a detailed and validated food
      frequency questionnaire. During a mean follow-up of 13.6 years (1985-2004), 2702
      cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid
      hemorrhages were identified in the national registries. RESULTS: After adjustment
      for age and cardiovascular risk factors, a high magnesium intake was associated
      with a statistically significant lower risk of cerebral infarction but not with
      intracerebral or subarachnoid hemorrhages. The multivariate relative risk of
      cerebral infarction was 0.85 (95% confidence interval, 0.76-0.97; P for trend =
      .004) for men in the highest quintile of magnesium intake compared with those in
      the lowest quintile. The inverse association between magnesium intake and
      cerebral infarction was stronger in men younger than 60 years (relative risk,
      0.76; 95% confidence interval, 0.64-0.89; P for interaction = .02). Calcium,
      potassium, and sodium intake was not significantly associated with risk of any
      subtype of stroke (P for trend > .05). CONCLUSION: These findings in male smokers
      suggest that a high magnesium intake may play a role in the primary prevention of
      cerebral infarction.

PMID- 18332290
TI  - Ongoing improvement in outcomes for patients diagnosed as having Non-Hodgkin
      lymphoma from the 1990s to the early 21st century.
AB  - BACKGROUND: Non-Hodgkin lymphoma (NHL) is the most common hematologic malignant
      neoplasm in adults. We use the novel technique of period analysis to disclose the
      most recent trends in survival among adults diagnosed as having NHL on the
      population level with minimum delay. METHODS: We estimated trends in 5- and 10
      year relative survival in patients 15 years or older diagnosed as having NHL in
      the United States between 1990 and 2004 using data from the Surveillance,
      Epidemiology, and End Results (SEER) program. We also estimated survival by age,
      location and histologic type of the tumor, sex, and race to further elucidate
      trends in survival in this disease. RESULTS: Overall, 5-year relative survival
      increased from 50.4% to 66.8%, and 10-year relative survival increased from 39.4%
      to 56.3% between 1990-1992 and 2002-2004. Improvements were most pronounced in
      patients younger than 45 years (+26.8 and +27.1 percentage points for 5- and 10
      year survival, respectively), but improvements were seen in all age groups, in
      both sexes, in both nodal and extranodal disease, and in both low-grade and high
      grade disease. Improvements in prognosis were less in black patients than in
      white patients, especially in younger black patients. CONCLUSIONS: Our period
      analysis discloses a strongly improved outlook for patients diagnosed as having
      NHL in recent years. Changes in treatment of the disease and a decrease in the
      number of human immunodeficiency virus-related NHL cases attributable to highly
      active antiretroviral therapy are probably primarily responsible for these
      improvements.

PMID- 18332291
TI  - A randomized trial of direct-to-patient communication to enhance adherence to
      beta-blocker therapy following myocardial infarction.
AB  - BACKGROUND: Although beta-blockers are routinely prescribed at hospital discharge
      after myocardial infarction (MI), patients' adherence has been shown to decline
      substantially over time. We sought to test the hypothesis that a simple, direct
      to-patient intervention can improve adherence to beta-blocker therapy following
      MI. METHODS: We conducted a cluster randomized controlled trial in 4
      geographically dispersed health maintenance organizations testing the hypothesis
      that a simple direct-to-patient intervention could improve adherence. The study
      was carried out from June 2004 to March 2005. The primary analyses were based on
      836 post-MI patients who were dispensed a beta-blocker prescription after
      discharge. The intervention consisted of 2 mailings 2 months apart describing the
      importance of beta-blocker use. The main outcomes were proportion of days covered
      with beta-blocker therapy and percentage of patients with at least 80% of days
      covered in the 9 months after the first mailing. Analyses were adjusted for age,
      sex, total medications dispensed, days between MI and intervention, and
      intervention site. RESULTS: Over the entire follow-up period, patients in the
      treatment arm had a mean absolute increase of 4.3% of days covered per month
      compared with patients in the control arm (a 5.7% relative change from baseline),
      representing 1.3 extra days (P = .04). Treatment patients were 17% more likely
      (relative risk, 1.17; 95% confidence interval, 1.02-1.29) to have 80% of days
      covered. For every 16 patients receiving the intervention, 1 additional patient
      would become adherent (80% or more days covered per month). CONCLUSION: A low
      cost, easily replicable effort to increase adherence can have a demonstrable
      impact on beta-blocker adherence following MI. Trial Registration
      clinicaltrials.gov Identifier: NCT00211172.

PMID- 18332293
TI  - Association of early follow-up after acute myocardial infarction with higher
      rates of medication use.
AB  - BACKGROUND: Early outpatient follow-up after acute myocardial infarction (AMI) is
      recommended in guidelines, but its relationship with the use of evidence-based
      therapies is unknown. METHODS: We evaluated 1516 patients hospitalized with AMI
      from the multicenter Prospective Registry Evaluating Outcomes After Myocardial
      Infarction: Events and Recovery registry. Early follow-up was defined as patient-
      reported visits with a primary care physician or cardiologist within 1 month
      after discharge. The primary outcomes were use of aspirin, beta-blockers,
      angiotensin-converting enzyme inhibitors, and statins in eligible patients at 6
      months. Multivariable analyses assessed the association between early follow-up
      and medication use at 6 months, adjusting for patient and clinical
      characteristics. Secondary analyses compared medication use at 6 months for
      patients receiving collaborative follow-up from a single provider vs those
      receiving follow-up from both provider types. RESULTS: Among the cohort, 34%
      reported no outpatient follow-up during the month following discharge. Rates of
      medication prescription among appropriate candidates were similar at hospital
      discharge for both follow-up groups. Compared with those not receiving early
      follow-up, those receiving early follow-up were more likely to be prescribed beta
      blockers (80.1% vs 71.3%; P = .001), aspirin (82.9% vs 77.1%; P = .01), or
      statins (75.9% vs 68.6%; P = .005) at 6 months. In multivariable analyses, a
      persistent relationship remained between early follow-up and beta-blocker use
      (risk ratio, 1.08; 95% confidence interval, 1.02-1.15). In secondary analyses,
      statin use was higher in patients receiving collaborative follow-up (risk ratio,
      1.11; 95% confidence interval, 1.01-1.22). CONCLUSIONS: Early outpatient follow
      up and collaborative follow-up after AMI is associated with higher rates of
      evidence-based medication use. Although further studies should assess whether
      this relationship is causal, these results support current guideline
      recommendations for follow-up after AMI.

PMID- 18332295
TI  - The Accreditation Council for Graduate Medical Education's limits on residents'
      work hours and patient safety. A study of resident experiences and perceptions
      before and after hours reductions.
AB  - BACKGROUND: Limiting resident work hours may improve patient safety, but
      unintended adverse effects are also possible. We sought to assess the impact of
      Accreditation Council for Graduate Medical Education resident work hour limits
      implemented on July 1, 2003, on resident experiences and perceptions regarding
      patient safety. METHODS: All trainees in 76 accredited programs at 2 teaching
      hospitals were surveyed in 2003 (preimplementation) and 2004 (postimplementation)
      regarding their work hours and patient load; perceived relation of work hours,
      patient load, and fatigue to patient safety; and experiences with adverse events
      and medical errors. Based on reported weekly duty hours, 13 programs experiencing
      substantial hours reductions were classified into a "reduced-hours" group. Change
      scores in outcome measures before and after policy implementation in the reduced
      hours programs were compared with those in "other programs" to control for
      temporal trends, using 2-way analysis of variance with interaction. RESULTS: A
      total of 1770 responses were obtained (response rate, 60.0%). Analysis was
      restricted to 1498 responses from respondents in clinical years of training.
      Residents in the reduced-hours group reported significant reductions in mean
      weekly duty hours (from 76.6 to 68.0 hours, P < .001), and the percentage working
      more than 80 hours per week decreased from 44.0% to 16.6% (P < .001). No
      significant increases in patient load while on call (patients admitted, covered,
      or cross covered) were observed. Between 2003 and 2004, there was a decrease in
      the proportion of residents in the reduced-hours programs indicating that working
      too many hours (63.2% vs 44.0%; P < .001) or cross covering too many patients
      (65.9% vs 46.9%; P = .001) contributed to mistakes in patient care. There were no
      significant reductions in these 2 measures in the other group, and the
      differences in differences were significant (P = .03 and P = .02, respectively).
      The number of residents in reduced-hours programs who reported committing at
      least 1 medical error within the past week remained high in both study years
      (32.9% in 2003 and 26.3% in 2004, P = .27). CONCLUSIONS: It is possible to reduce
      residents' hours without increasing patient load. Doing so may reduce the extent
      to which fatigue affects patient safety as perceived by these frontline
      providers.

PMID- 18332296
TI  - Geographic variation and risk of skin cancer in US women. Differences between
      melanoma, squamous cell carcinoma, and basal cell carcinoma.
AB  - BACKGROUND: Occurrences of melanoma, squamous cell carcinoma (SCC), and basal
      cell carcinoma (BCC) have been associated with varying geography. Our goal was to
      evaluate differences in risk of these skin cancers according to residence at
      varying UV indices at 3 time points. METHODS: Prospective 1984-2002 study of 84
      836 female nurses who lived in different UV index regions of the United States at
      birth and at 15 or 30 years of age. The outcome measure was diagnosis of
      melanoma, SCC, or BCC. RESULTS: During the 18-year study, 420 cases of melanoma,
      863 cases of SCC, and 8215 cases of BCC occurred. At 30 years of age, age
      adjusted risks for SCC were 1.47 (95% confidence interval [CI], 1.22-1.76) and
      1.90 (95% CI, 1.51-2.36) for women residing in states with a UV index of 6
      (medium) and 7 or more (high), respectively. Although elevated, the age-adjusted
      risk of BCC at 30 years of age associated with residence in these states was
      substantially less. Although the risk of melanoma was not elevated for women
      living in these states at 30 years of age, it was significantly elevated among
      women living in states with UV indices of 6 at birth and at 15 years of age.
      There was no material change in risk estimates with multivariate adjustment. For
      women who reported living in states with UV indices of 7 or more at all 3 time
      points, the multivariate risk of SCC was highest. CONCLUSIONS: The risk of SCC is
      independently affected by residence in locations with medium and high UV indices;
      the gradient of risk is weaker for BCC; and the risk of melanoma does not change
      significantly across this gradient.

PMID- 18332297
TI  - The anticholinergic risk scale and anticholinergic adverse effects in older
      persons.
AB  - BACKGROUND: Adverse effects of anticholinergic medications may contribute to
      events such as falls, delirium, and cognitive impairment in older patients. To
      further assess this risk, we developed the Anticholinergic Risk Scale (ARS), a
      ranked categorical list of commonly prescribed medications with anticholinergic
      potential. The objective of this study was to determine if the ARS score could be
      used to predict the risk of anticholinergic adverse effects in a geriatric
      evaluation and management (GEM) cohort and in a primary care cohort. METHODS:
      Medical records of 132 GEM patients were reviewed retrospectively for medications
      included on the ARS and their resultant possible anticholinergic adverse effects.
      Prospectively, we enrolled 117 patients, 65 years or older, in primary care
      clinics; performed medication reconciliation; and asked about anticholinergic
      adverse effects. The relationship between the ARS score and the risk of
      anticholinergic adverse effects was assessed using Poisson regression analysis.
      RESULTS: Higher ARS scores were associated with increased risk of anticholinergic
      adverse effects in the GEM cohort (crude relative risk [RR], 1.5; 95% confidence
      interval [CI], 1.3-1.8) and in the primary care cohort (crude RR, 1.9; 95% CI,
      1.5-2.4). After adjustment for age and the number of medications, higher ARS
      scores increased the risk of anticholinergic adverse effects in the GEM cohort
      (adjusted RR, 1.3; 95% CI, 1.1-1.6; c statistic, 0.74) and in the primary care
      cohort (adjusted RR, 1.9; 95% CI, 1.5-2.5; c statistic, 0.77). CONCLUSION: Higher
      ARS scores are associated with statistically significantly increased risk of
      anticholinergic adverse effects in older patients.

PMID- 18332298
TI  - Screening mammography in older women. Effect of wealth and prognosis.
AB  - BACKGROUND: Wealthy women have higher rates of screening mammography than poor
      women do. Screening mammography is beneficial for women with substantial life
      expectancies, but women with limited life expectancies are unlikely to benefit.
      It is unknown whether higher screening rates in wealthy women are due to
      increased screening in women with substantial life expectancies, limited life
      expectancies, or both. This study examines the relationship between wealth and
      screening mammography use in older women according to life expectancy. METHODS: A
      cohort study was performed of 4222 women 65 years or older with Medicare
      participating in the 2002 and 2004 Health and Retirement Survey. Women were
      categorized according to wealth and life expectancy (based on 5-year prognosis
      from a validated prognostic index). The outcome was self-reported receipt of
      screening mammography within 2 years. RESULTS: Overall, within 2 years, 68% of
      women (2871 of 4222) received a screening mammogram. Screening was associated
      with wealth (net worth, > $100 000) and good prognosis (< or = 10% probability of
      dying in 5 years). Screening mammography was more common among wealthy women than
      among poor women (net worth, < $10 000) both for women with good prognosis (82%
      vs 68%; P < .001) and for women with limited prognoses (> or = 50% probability of
      dying in 5 years) (48% vs 32%; P = .02). These associations remained after
      multivariate analysis accounting for age, race, education, proxy report, and
      rural residence. CONCLUSIONS: Poorer older women with favorable prognoses are at
      risk of not receiving screening mammography when they are likely to benefit.
      Wealthier older women with limited prognoses are often screened when they are
      unlikely to benefit.

PMID- 18332299
TI  - Adjuvant chemotherapy after resection in elderly Medicare and Medicaid patients
      with colon cancer.
AB  - BACKGROUND: This study investigated the influence of Medicaid enrollment on the
      receipt and completion of adjuvant chemotherapy and the likelihood of evaluation
      by an oncologist for those patients who do not initiate chemotherapy. METHODS:
      Medicaid and Medicare administrative data were merged with the Michigan Tumor
      Registry to extract a sample of patients who had resection for a first primary
      colon tumor diagnosed between January 1, 1997, and December 31, 2000 (n = 4765).
      We used unadjusted and adjusted logistic regression to assess the relationship
      between Medicaid enrollment and the outcomes of interest. RESULTS: Relative to
      Medicare patients, Medicaid patients were less likely to initiate chemotherapy
      (odds ratio, 0.50; 95% confidence interval, 0.39-0.65) or complete chemotherapy
      (odds ratio, 0.52; 95% confidence interval, 0.31-0.85). When the sample was
      restricted to patients with TNM-staged disease, Medicaid patients were less
      likely to initiate chemotherapy. Older patients and patients with comorbidities
      were also less likely to initiate or, in some cases, to complete chemotherapy.
      CONCLUSION: Medicaid enrollment is associated with disparate colon cancer
      treatment, which likely compromises the long-term survival of these patients.

PMID- 18332300
TI  - Randomized controlled trial of web-based alcohol screening and brief intervention
      in primary care.
AB  - BACKGROUND: There is compelling evidence supporting screening and brief
      intervention (SBI) for hazardous drinking, yet it remains underused in primary
      health care. Electronic (computer or Web-based) SBI (e-SBI) offers the prospects
      of ease and economy of access. We sought to determine whether e-SBI reduces
      hazardous drinking. METHODS: We conducted a randomized controlled trial in a
      university primary health care service. Participants were 975 students (age
      range, 17-29 years) screened using the Alcohol Use Disorders Identification Test
      (AUDIT). Of 599 students who scored in the hazardous or harmful range, 576 (300
      of whom were women) consented to the trial and were randomized to receive an
      information pamphlet (control group), a Web-based motivational intervention
      (single-dose e-SBI group), or a Web-based motivational intervention with further
      interventions 1 and 6 months later (multidose e-SBI group). RESULTS: Relative to
      the control group, the single-dose e-SBI group at 6 months reported a lower
      frequency of drinking (rate ratio [RR], 0.79; 95% confidence interval [CI], 0.68
      0.94), less total consumption (RR, 0.77; 95% CI, 0.63-0.95), and fewer academic
      problems (RR, 0.76; 95% CI, 0.64-0.91). At 12 months, statistically significant
      differences in total consumption (RR, 0.77; 95% CI, 0.63-0.95 [equivalent to 3.5
      standard drinks per week]) and in academic problems (RR, 0.80; 95% CI, 0.66-0.97)
      remained, and the AUDIT scores were 2.17 (95% CI, -1.10 to -3.24) points lower.
      Relative to the control group, the multidose e-SBI group at 6 months reported a
      lower frequency of drinking (RR, 0.85; 95% CI, 0.73-0.98), less total consumption
      (RR, 0.79; 95% CI, 0.64-0.97 [equivalent to 3.0 standard drinks per week]),
      reduced episodic heavy drinking (RR, 0.65; 95% CI, 0.45-0.93), and fewer academic
      problems (RR, 0.78; 95% CI, 0.65-0.93). At 12 months, statistically significant
      differences in academic problems remained (RR, 0.75; 95% CI, 0.62-0.90), while
      the AUDIT scores were 2.02 (95% CI, -0.97 to -3.10) points lower. CONCLUSIONS:
      Single-dose e-SBI reduces hazardous drinking, and the effect lasts 12 months.
      Additional sessions seem not to enhance the effect. Trial Registration
      www.anzctr.org.au Identifier:ACTRN012607000103460.

PMID- 18332301
TI  - Dealing with delicate issues in continuous deep sedation. Varying practices among
      Dutch medical specialists, general practitioners, and nursing home physicians.
AB  - BACKGROUND: This article examines delicate issues in continuous deep sedation
      (CDS) from the perspectives of different types of physicians. The following
      sensitive issues involved in CDS were investigated: artificial hydration,
      sedation for nonphysical discomfort, the relationship between CDS and euthanasia,
      and patient involvement in decision making for CDS. METHODS: A structured
      retrospective questionnaire concerning the most recent case of CDS during the
      past 12 months was sent to a sample of medical specialists (n = 727), general
      practitioners (n = 626), and nursing home physicians (n = 111). RESULTS: Response
      rates were 26.4% for medical specialists, 37.4% for general practitioners, and
      59.5% for nursing home physicians. Indications for CDS differed among the types
      of physicians. General practitioners (25.0%) were most often confronted with a
      patient request for euthanasia before starting CDS compared with medical
      specialists (8.9%) and nursing home physicians (6.5%). A decision to forgo
      artificial hydration in CDS was more often made by nursing home physicians
      (91.3%) compared with medical specialists (53.7%) and general practitioners
      (51.2%). Shorter survival was found for patients sedated for nonphysical
      discomfort (vs other patients) by general practitioners. Among all patients,
      74.5% were involved in decision making before the start of CDS. CONCLUSIONS: The
      present study demonstrates notable differences in CDS practice among various
      types of physicians. To what extent this is related to different patient
      populations or to different expertise requires further investigation. The use of
      CDS for nonphysical discomfort calls for critical examination to avoid ambiguous
      practice.

PMID- 18332302
TI  - The representation of women on the editorial boards of major medical journals: a
      35-year perspective.

PMID- 18332303
TI  - Neither freedom nor autonomy without beneficence.

PMID- 18332304
TI  - Low-dose rosiglitazone in patients with type 2 diabetes mellitus requiring
      insulin therapy.

PMID- 18332305
TI  - Laboratory-defined aspirin resistance and recurrent cardiovascular events.

PMID- 18332306
TI  - Acupuncture trial lacks a priori rationale to refute null hypothesis.

PMID- 18332307
TI  - Is aspirin resistance due to noncompliance?

PMID- 18332308
TI  - Acupuncture ineffective, attention effective?

PMID- 18332309
TI  - Intraocular pressure-lowering effects and safety of topical administration of a
      selective ROCK inhibitor, SNJ-1656, in healthy volunteers.
AB  - OBJECTIVE: To investigate the effects and safety of topical administration of an
      ophthalmic solution of a selective Rho-associated coiled coil-forming protein
      kinase (ROCK) inhibitor, SNJ-1656, 0.003% to 0.1%, in healthy male adult
      volunteers. DESIGN: Randomized, double-masked, group-comparison, phase 1 clinical
      study. In the initial single-instillation trial, 45 healthy volunteers were
      randomly subdivided into 5 groups and treated with SNJ-1656 in concentrations of
      0.003%, 0.01%, 0.03%, 0.05%, and 0.1% in stepwise fashion. In the repeated
      instillation trial, 36 healthy volunteers were assigned to receive SNJ-1656
      ophthalmic solution at the following concentrations and dosages: 0.05% once
      daily, 0.1% once daily, 0.05% twice daily, or 0.1% twice daily. In our studies,
      the administration of the solution and subsequent examinations (including
      intraocular pressure [IOP] measurements) were performed in a double-masked
      fashion. RESULTS: After single instillation of placebo or SNJ-1656, in
      concentrations of 0.003%, 0.01%, 0.03%, 0.05%, and 0.1%, the changes in IOP from
      the baseline were -0.91, -1.18, -1.48, - 2.20 (P = .04 vs placebo), -1.48, and 
      1.98 mm Hg, respectively, at 2 hours, and -0.63,-0.95, -1.79, -2.26 (P = .01 vs
      placebo), -1.95, and -3.00 mm Hg (P < .001 vs placebo) respectively, at 4 hours.
      Significant IOP reductions after repeated instillation were also found. On
      slitlamp examination during the trial, there were no significant adverse findings
      except hyperemia of the bulbar and palpebral conjunctiva after instillation.
      CONCLUSION: This clinical study demonstrated that SNJ-1656 is a safe topical
      agent effective in reducing IOP in human eyes.

PMID- 18332310
TI  - Macular dystrophy associated with the A3243G mitochondrial DNA mutation. Distinct
      retinal and associated features, disease variability, and characterization of
      asymptomatic family members.
AB  - OBJECTIVES: To determine (1) detailed retinal and audiological features of
      probands harboring the A3243G mitochondrial DNA mutation (m.3243A>G) and their
      asymptomatic maternal relatives, (2) intrafamilial and interfamilial phenotypic
      variability, and (3) the presence of other systemic features. METHODS: Seven
      probands harboring the A3243G mitochondrial DNA mutation and 36 asymptomatic
      maternal relatives were ascertained. Participants underwent ophthalmologic
      examination, fundus photography, autofluorescence imaging, and audiological
      evaluation and completed a questionnaire. Blood samples were taken to test for
      diabetes, determine renal function, and screen relatives for the A3243G mutation.
      RESULTS: The A3243G mutation was associated with both intrafamilial and
      interfamilial variable expressivity regarding retinal appearance, hearing loss,
      diabetes, and other systemic features. The most common macular appearance in
      maternal relatives (one-third of those positive for the mutation) was mild
      abnormalities of the retinal pigment epithelium (more clearly identified using
      autofluorescence), which may therefore be a useful clinical indicator suggesting
      positive mutation status. Four probands and 13 mutation-positive relatives were
      found to have evidence of significant bilateral, cochlear, symmetrical age
      adjusted hearing loss, predominantly affecting high frequencies. CONCLUSIONS:
      Hearing loss and macular disturbance were the most frequent findings in mutation
      positive participants, with 95% of mutation-positive relatives having hearing
      loss. Diabetes was the least frequent finding. Patients with progressive hearing
      loss may merit ophthalmologic assessment to detect retinal abnormalities
      consistent with the A3243G mutation. Conversely, patients with macular features
      in keeping with the A3243G mutation should have audiological testing, even in the
      absence of diabetes or a positive family history.

PMID- 18332311
TI  - Correlation of functional impairment and morphological alterations in patients
      with group 2A idiopathic juxtafoveal retinal telangiectasia.
AB  - OBJECTIVE: To correlate functional impairment with morphological alterations in
      patients with group 2A idiopathic juxtafoveal retinal telangiectasia. METHODS: As
      part of the Macular Telangiectasia Project, a cohort of 10 patients underwent
      additional functional testing and imaging studies including photopic and scotopic
      fine matrix mapping, microperimetry, reflectance, and autofluorescence imaging
      with scanning laser ophthalmoscopy. RESULTS: From clinical stage 2 to 5, scotopic
      central function was reduced, which corresponded to depletion of macular pigment
      density. From clinical stage 3 onward, severe photopic and scotopic scotomata
      with up to 30 dB of loss were found next to fixation and were not totally
      confined to abnormalities seen with standard imaging modalities. The number of
      test points with loss of 10 dB or more was significantly greater for scotopic
      testing than for photopic testing (P = .007, Wilcoxon signed rank test).
      CONCLUSIONS: Rod function may be more severely affected than cone function in
      patients with group 2A idiopathic juxtafoveal retinal telangiectasia, and this
      may occur early in the disease progression. Severe reduction in retinal
      sensitivity is spatially confined to morphological alterations seen with scanning
      laser ophthalmoscopy imaging. The findings imply that idiopathic juxtafoveal
      retinal telangiectasia is not solely a vascular disease and that early neuronal
      involvement may be implicated in the pathogenesis of the disease.

PMID- 18332312
TI  - Age at onset curves of retinitis pigmentosa.
AB  - OBJECTIVE: To calculate age at onset curves of retinitis pigmentosa (RP) to
      resolve the difficulty in calculating the recurrence risk in a family. Retinitis
      pigmentosa is a common hereditary retinal disease that leads to blindness. It is
      a slow-onset disease, and family members of patients sometimes develop RP later.
      METHODS: We studied 370 patients with typical RP. The age at onset was defined as
      when the patient's RP was diagnosed by an ophthalmologist. After confirmation
      that the age at onset came from normal distribution, we drew the age at onset
      curves. RESULTS: The average age when patients were diagnosed with RP was 35.1
      years, and the median age was 36.5. The onset ratio straightly increased with age
      until 65 years, so the onset ratio was relatively low at young ages. CONCLUSIONS:
      The age at onset curves are quite simple and useful tools that facilitate
      counseling at an RP clinic. Without them, the recurrence risk would be
      misleading.

PMID- 18332313
TI  - Penetration of voriconazole, 1%, eyedrops into human aqueous humor: a prospective
      open-label study.
AB  - OBJECTIVE: To determine the therapeutic efficacy of adjuvant use of voriconazole,
      1%, eyedrops in the treatment of refractory fungal keratitis. METHODS: A
      prospective open-label trial was conducted to determine voriconazole levels
      obtained in human aqueous humor after administration of a 1% solution, preserved
      with 0.01% benzalkonium chloride, every 6 hours for 3 days, or hourly for 4
      doses. Ten participants were selected among patients scheduled to undergo
      elective anterior segment surgery, and samples were tested using validated high
      performance liquid chromatography. RESULTS: The mean (SD) voriconazole
      concentrations after hourly dosing (n = 5) was 1.90 (1.12) microg/mL and after a
      single dosing every 6 hours (n = 5) was 0.94 (1.21) microg/mL, respectively. The
      mean (SD) sampling times after the last administration of eyedrops were 1.1 (0.5)
      hours after hourly dosing and 2.1 (0.6) hours after a single dosing every 6
      hours. CONCLUSIONS: Voriconazole, 1%, eyedrops are well tolerated and penetrate
      into human aqueous humor when administered at hourly or 6-hourly intervals. They
      are effective in treating Candida and Aspergillus keratitis, are substantially
      more affordable than oral therapy, and have less potential to cause systemic
      adverse effects.

PMID- 18332314
TI  - Effect of human tears on acanthamoeba-induced cytopathic effect.
AB  - OBJECTIVE: To determine whether tears of healthy individuals provide protection
      against Acanthamoeba-induced cytopathic effect (CPE) in vitro. METHODS:
      Acanthamoebae were added to confluent cultures of corneal epithelium in 24-well
      plates, and co-cultures were incubated overnight in a serum-free medium
      containing varying amounts of tears or immunoglobulin A (IgA)-depleted tears. At
      the end of the incubation period, the cells were stained with Giemsa, and the
      extent of target cell damage (ie, CPE) was quantified. RESULTS: Acanthamoebae
      produced extensive CPE. The presence of even a low concentration of tears (10
      microL of undiluted tears per milliliter of media) almost completely inhibited
      Acanthamoeba-induced CPE. The CPE was inhibited by pretreatment of the parasites
      with tears. In contrast, the pretreatment of host cells with tears was not
      protective. This finding suggests that the target of the inhibitory factor is the
      parasite. IgA-depleted tears also inhibited Acanthamoeba-induced CPE, albeit with
      a lower potency than total tears. CONCLUSION: In addition to known IgA-dependent
      protective factors, human tears contain factors that inhibit Acanthamoeba-induced
      CPE independently of IgA. Clinical Relevance Identification and characterization
      of factors that protect against Acanthamoeba-induced CPE should help in the
      development of novel, rationally designed strategies to manage and protect
      against keratitis.

PMID- 18332317
TI  - Open-angle glaucoma and mortality: The Barbados Eye Studies.
AB  - OBJECTIVE: To evaluate the relationship between open-angle glaucoma (OAG) and
      mortality in a black population at 9-years' follow-up. DESIGN: Population-based
      cohort study of 4092 black participants (aged 40-84 years at baseline) in the
      Barbados Eye Studies. Open-angle glaucoma was defined by visual field defects and
      optic disc damage, based on standardized examinations and photograph gradings.
      Ocular hypertension was defined by an intraocular pressure greater than 21 mm Hg
      or treatment, without OAG damage. Mortality was ascertained from death
      certificates. Cox proportional hazards regression analyses determined
      associations with mortality. RESULTS: After 9 years, 764 (19%) participants were
      deceased. Mortality was unrelated to overall OAG at baseline (n = 300) after
      adjustment for confounders. However, cardiovascular mortality tended to increase
      in persons with previously diagnosed/treated OAG (n = 141; relative risk [RR],
      1.38, P = .07) and was significantly higher with treatment involving timolol
      maleate (RR, 1.91, P = .04). Cardiovascular deaths also tended to increase in
      persons with ocular hypertension at baseline (n = 498; RR, 1.28, P = .06).
      CONCLUSIONS: In this black population, cardiovascular mortality tended to
      increase in persons with previously diagnosed/treated OAG and ocular
      hypertension. The excess mortality associated with timolol maleate treatment of
      OAG, also found in a white population, warrants further investigation.

PMID- 18332316
TI  - Associations between age-related nuclear cataract and lutein and zeaxanthin in
      the diet and serum in the Carotenoids in the Age-Related Eye Disease Study, an
      Ancillary Study of the Women's Health Initiative.
AB  - OBJECTIVE: To evaluate associations between nuclear cataract (determined from
      slitlamp photographs between May 2001 and January 2004) and lutein and zeaxanthin
      in the diet and serum in patients between 1994 and 1998 and macula between 2001
      and 2004. DESIGN: A total of 1802 women aged 50 to 79 years in Iowa, Wisconsin,
      and Oregon with intakes of lutein and zeaxanthin above the 78th (high) and below
      the 28th (low) percentiles in the Women's Health Initiative Observational Study
      (1994-1998) were recruited 4 to 7 years later (2001-2004) into the Carotenoids in
      Age-Related Eye Disease Study. RESULTS: Women in the group with high dietary
      levels of lutein and zeaxanthin had a 23% lower prevalence of nuclear cataract
      (age-adjusted odds ratio, 0.77; 95% confidence interval, 0.62-0.96) compared with
      those with low levels. Multivariable adjustment slightly attenuated the
      association (odds ratio, 0.81; 95% confidence interval, 0.65-1.01). Women in the
      highest quintile category of diet or serum levels of lutein and zeaxanthin as
      compared with those in the lowest quintile category were 32% less likely to have
      nuclear cataract (multivariable-adjusted odds ratio, 0.68; 95% confidence
      interval, 0.48-0.97; P for trend = .04; and multivariable-adjusted odds ratio,
      0.68; 95% confidence interval, 0.47-0.98; P for trend = .01, respectively). Cross
      sectional associations with macular pigment density were inverse but not
      statistically significant. CONCLUSIONS: Diets rich in lutein and zeaxanthin are
      moderately associated with decreased prevalence of nuclear cataract in older
      women. However, other protective aspects of such diets may in part explain these
      relationships.

PMID- 18332318
TI  - A novel variant of combined granular-lattice corneal dystrophy associated with
      the Met619Lys mutation in the TGFBI gene.
AB  - OBJECTIVE: To report a novel mutation in TGFBI (GenBank NM_000358), p.Met619Lys,
      associated with a variant of combined granular-lattice corneal dystrophy.
      METHODS: Slitlamp examination and DNA collection from the proband and affected
      and unaffected relatives. All 17 exons of TGFBI were amplified and sequenced in
      the proband. Exon 14 was amplified and sequenced in the proband's family members
      and in 100 controls. Histopathologic examination of the excised corneal buttons
      from the proband and 3 family members was also performed. RESULTS: Affected
      individuals demonstrated an age-dependent phenotype, with the progression from
      central subepithelial needlelike deposits in younger individuals to polymorphic
      anterior stromal opacities in older family members. Screening of TGFBI in the
      proband demonstrated a novel mutation, p.Met619Lys, which was also present in all
      affected family members. Histopathologic examination revealed stromal deposits
      that stained with the Congo red and Masson trichrome stains as well as an
      antibody to the protein product of TGFBI. CONCLUSIONS: We present a unique
      corneal dystrophy phenotype associated with the novel p.Met619Lys mutation in
      TGFBI. Clinical Relevance The atypical and variable phenotype and the
      demonstration of both hyaline and amyloid stromal deposits indicate that neither
      clinical nor histopathologic features may be relied on to accurately diagnose and
      classify the corneal dystrophies.

PMID- 18332319
TI  - Discordant phenotypes in fraternal twins having an identical mutation in exon
      ORF15 of the RPGR gene.
AB  - OBJECTIVE: To report discordant phenotypes, resulting from the same mutation in
      exon ORF15 (GenBank AF286472) of the retinitis pigmentosa GTPase regulator gene
      (RPGR) (GenBank U57629), in 2 presumed dizygotic twin brothers with X-linked
      retinal disease. METHODS: The 2 brothers underwent complete ophthalmic
      examination that included best-corrected visual acuity, slitlamp biomicroscopy,
      and detailed fundus examination. Visual field recording using Goldmann kinetic
      perimetry and a full-field electroretinogram were also obtained in both patients.
      Mutational screening was performed for RPGR because of an X-linked pattern of
      inheritance indicated by pedigree analysis. RESULTS: One brother had a phenotypic
      expression of cone-rod dystrophy, while the other exhibited X-linked retinitis
      pigmentosa. A 1-nucleotide deletion was identified in the 3' region of exon ORF15
      of RPGR (ORF15 + 1339delA). CONCLUSIONS: An identical mutation in RPGR-ORF15
      manifested distinct clinical phenotypes in individuals of the same family. Our
      data provide strong evidence in support of additional modifier genes that can
      produce diverse disease phenotypes in patients with RPGR mutations. CLINICAL
      RELEVANCE: The clinical observation of different retinal phenotypes in a family
      with the same mutation in exon ORF15 of RPGR implicates the potential importance
      of modifier genes for the phenotypic expression of this form of X-linked retinal
      disease.

PMID- 18332320
TI  - Novel and recurrent KIF21A mutations in congenital fibrosis of the extraocular
      muscles type 1 and 3.
AB  - OBJECTIVE: To characterize the disease-causing mutations and associated clinical
      phenotypes in 5 Chinese families with congenital fibrosis of the extraocular
      muscles (CFEOM). METHODS: Ophthalmic investigations included visual acuity,
      levator function, documentation of compensatory head position, ocular motility,
      and slitlamp and fundus examinations. The kinesin family member 21A gene (KIF21A)
      was sequenced for mutation detection. Genotyping and linkage analysis were
      performed for the KIF21A/FEOM1 and FEOM3 loci. RESULTS: Four families were
      clinically classified as having CFEOM type 1 (CFEOM1) with full expression of
      severe ptosis and ophthalmoplegia. One family had CFEOM type 3 (CFEOM3) with
      typically varying expression of phenotypes between individuals. Recurrent
      heterozygous KIF21A mutations were identified in 2 CFEOM1 families (2860C>T) and
      the CFEOM3 family (2861G>A). In another CFEOM1 family, a novel missense mutation
      (84C>G, C28W) was revealed. CONCLUSIONS: The novel KIF21A mutation 84C>G
      demonstrated in a CFEOM1 family affects the kinesin motor domain, supporting that
      mutations may also occur outside the commonly involved coiled-coil domain. The
      2861G>A mutation found in a CFEOM3 family has been previously reported in CFEOM1,
      further supporting that different phenotypes can arise from identical mutations.
      Clinical Relevance Clinical and genetic characterization are complementary tools
      for diagnostic, prognostic, and treatment purposes in CFEOM.

PMID- 18332321
TI  - New mutation, P575L, in the GUCY2D gene in a family with autosomal dominant
      progressive cone degeneration.
AB  - OBJECTIVES: To clinically characterize the retinal abnormalities and identify the
      mutation causing an autosomal dominant cone degeneration in an African American
      family. METHODS: Clinical characterization of family members using fundus
      photography, fluorescein angiography, and electrophysiological testing. Standard
      molecular genetic methods were used, including segregation analysis and DNA
      sequencing of candidate genes. Genetic mutation screening was performed in 20
      individuals: 10 clinically unaffected and 10 affected. RESULTS: The affected
      family members had findings consistent with a primary cone degeneration. A novel
      mutation, P575L, was found in exon 8 of the GUCY2D gene in 12 members of this
      family. CONCLUSIONS: In addition to finding a previously undescribed mutation in
      GUCY2D, 2 of the family members who were thought to be unaffected through routine
      clinical examinations also had this mutation. These findings suggest that
      autosomal dominant cone degeneration in this family demonstrated age-dependent
      penetrance, which appears incomplete. This is the first African American family
      reported with a mutation in GUCY2D. Because the disease in this family and the
      one we previously described is primarily a cone degeneration, this disease should
      be more properly classified as cone degeneration and be called cone degeneration
      2. CLINICAL RELEVANCE: This study helps to expand the phenotype of the disease
      and help clinicians identify patients with cone degenerations.

PMID- 18332322
TI  - Microkeratome-assisted anterior lamellar keratoplasty.
AB  - Microkeratome-assisted anterior lamellar keratoplasty has emerged as a surgical
      option for conditions affecting the clarity of the outer 200 mum of the cornea.
      Herein we describe the outcome of a simple procedure in which the excimer laser
      can be used to augment deep tissue removal after both recipient bed and donor
      graft are prepared with the microkeratome. Our noncomparative interventional case
      series involved 5 eyes of 4 patients with lattice corneal dystrophy who underwent
      microkeratome-assisted anterior lamellar keratoplasty. Outcome measures include
      preoperative and postoperative best spectacle-corrected Snellen visual acuity.
      Visante ocular coherence tomography data are reported for several of the
      patients.

PMID- 18332323
TI  - Cytogenetics in the management of uveal melanoma: are we there yet?

PMID- 18332324
TI  - The future promise and the current reality of genetic prognostication in patients
      with uveal melanoma.

PMID- 18332325
TI  - Role of cytogenetics in management of uveal melanoma.

PMID- 18332326
TI  - Association Between LOXL1 and pseudoexfoliation.

PMID- 18332327
TI  - Genomic promise: personalized medicine for ophthalmology.

PMID- 18332328
TI  - Genomics in the era of molecular ophthalmology: reflections on the National
      Ophthalmic Disease Genotyping Network (eyeGENE).

PMID- 18332329
TI  - Understanding the critical importance of diagnosis in the measurement of quality
      of care.

PMID- 18332330
TI  - Clinical manifestation of a novel PAX6 mutation Arg128Pro.

PMID- 18332331
TI  - Developmental glaucoma with chromosomal abnormalities of 9p deletion and 13q
      duplication.

PMID- 18332332
TI  - Autoantibodies against bestrophin in a patient with vitelliform paraneoplastic
      retinopathy and a metastatic choroidal malignant melanoma.

PMID- 18332333
TI  - Central corneal thickness and optic disc hemorrhages: the Beijing Eye Study.

PMID- 18332334
TI  - Primary clear cell carcinoma of the conjunctiva.

PMID- 18332335
TI  - Giant intrascleral cyst treated with trichloroacetic acid.

PMID- 18332336
TI  - Hypopigmentary fundus changes with cutaneous vitiligo.

PMID- 18332339
TI  - Expanding ventricles may detect preclinical Alzheimer disease.

PMID- 18332340
TI  - Playing doctor well.

PMID- 18332341
TI  - Deficient sequencing of pantomimes in apraxia.
AB  - OBJECTIVE: Typically, the apraxic deficit of patients with left hemisphere damage
      is more pronounced for complex, i.e., sequential actions, than for simple ones.
      This impaired action sequencing can be attributed to a faulty selection of
      movements, a deficit of shifting motor attention, or, alternatively, disturbed
      processing of action-related temporal information. METHODS: Twenty patients with
      lesions of the left hemisphere with and without apraxia and 20 patients with
      right hemisphere lesions with and without neglect were asked to detect errors in
      the sequential structure or the spatial configuration of object-related complex
      actions, visually presented as actions with objects or pantomimes. RESULTS: As
      expected, both patients with apraxia and neglect performed worse than patients
      without neuropsychological deficit (or elderly control subjects, n = 10). Side of
      lesion per se did not influence error rate. In contrast, left hemisphere-damaged
      patients with apraxia showed a specific deficit in detecting errors in the
      sequential structure of complex pantomime actions. In accordance with functional
      imaging studies showing an involvement of the left parietal cortex in movement
      related temporal processing, lesion analysis of the patients with left hemisphere
      lesions revealed that damage to the inferior parietal cortex (angular gyrus) was
      associated with this specific impairment in detecting sequential errors in
      pantomime action. CONCLUSIONS: The data suggest that impaired processing of
      temporal movement information due to lesions of the left inferior parietal cortex
      contributes to the complex action sequencing deficit in apraxia.

PMID- 18332342
TI  - Intraventricular hemorrhage: Anatomic relationships and clinical implications.
AB  - BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is frequently associated
      with intraventricular hemorrhage (IVH), which is an independent predictor of poor
      outcome. The purpose of this study was to examine the relationship between ICH
      volume and anatomic location to IVH, and to determine if ICH decompression into
      the ventricle is truly beneficial. METHODS: We retrospectively analyzed the CT
      scans and charts of all patients with ICH admitted to our stroke center over a 3
      year period. Outcome data were collected using our prospective stroke registry.
      RESULTS: We identified 406 patients with ICH. A total of 45% had IVH. Thalamic
      and caudate locations had the highest IVH frequency (69% and 100%). ICH volume
      and ICH location were predictors of IVH (p < 0.001). Within each location,
      decompression ranges (specific volume ranges where ventricular rupture tends to
      occur) were established. Patients with IVH were twice as likely to have a poor
      outcome (discharge modified Rankin scale of 4 to 6) (OR 2.25, p = 0.001) when
      compared to patients without IVH. Caudate location was associated with a good
      outcome despite 100% incidence of IVH. Spontaneous ventricular decompression was
      not associated with better outcome, regardless of parenchymal volume reduction (p
      = 0.72). CONCLUSIONS: Intraventricular hemorrhage (IVH) occurs in nearly half of
      patients with spontaneous intracerebral hemorrhage (ICH) and is related to ICH
      volume and location. IVH is likely to occur within the "decompression ranges"
      that take into account both ICH location and volume. Further, spontaneous
      ventricular decompression does not translate to better clinical outcome. This
      information may prove useful for future ICH trials, and to the clinician
      communicating with patients and families.

PMID- 18332343
TI  - The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic
      features.
AB  - BACKGROUND: Varicella zoster virus (VZV) vasculopathy produces stroke secondary
      to viral infection of cerebral arteries. Not all patients have rash before
      cerebral ischemia or stroke. Furthermore, other vasculitides produce similar
      clinical features and comparable imaging, angiographic, and CSF abnormalities.
      METHODS: We review our 23 published cases and 7 unpublished cases of VZV
      vasculopathy. All CSFs were tested for VZV DNA by PCR and anti-VZV IgG antibody
      and were positive for either or both. RESULTS: Among 30 patients, rash occurred
      in 19 (63%), CSF pleocytosis in 20 (67%), and imaging abnormalities in 29 (97%).
      Angiography in 23 patients revealed abnormalities in 16 (70%). Large and small
      arteries were involved in 15 (50%), small arteries in 11 (37%), and large
      arteries in only 4 (13%) of 30 patients. Average time from rash to neurologic
      symptoms and signs was 4.1 months, and from neurologic symptoms and signs to CSF
      virologic analysis was 4.2 months. CSF of 9 (30%) patients contained VZV DNA
      while 28 (93%) had anti-VZV IgG antibody in CSF; in each of these patients,
      reduced serum/CSF ratio of VZV IgG confirmed intrathecal synthesis. CONCLUSIONS:
      Rash or CSF pleocytosis is not required to diagnose varicella zoster virus (VZV)
      vasculopathy, whereas MRI/CT abnormalities are seen in almost all patients. Most
      patients had mixed large and small artery involvement. Detection of anti-VZV IgG
      antibody in CSF was a more sensitive indicator of VZV vasculopathy than detection
      of VZV DNA (p < 0.001). Determination of optimal antiviral treatment and benefit
      of concurrent steroid therapy awaits studies with larger case numbers.

PMID- 18332344
TI  - Racial differences in idiopathic intracranial hypertension.
AB  - OBJECTIVE: To evaluate racial differences in idiopathic intracranial hypertension
      (IIH). METHODS: Medical records of all consecutive patients with definite IIH
      seen between 1989 and 2006 were reviewed. Demographics, associated factors, and
      visual function at presentation and follow-up were collected. Black patients were
      compared to non-black patients. RESULTS: We included 450 patients (197 black, 253
      non-black). Obesity, systemic hypertension, anemia, and sleep apnea were more
      common in black patients than in non-black patients (p </= 0.01). CSF opening
      pressure was higher in black patients (40 vs 34 cm CSF, p < 0.001). Visual
      acuity, visual field loss, and degree of papilledema at presentation and follow
      up were worse in black patients (p </= 0.01). Diagnostic and therapeutic measures
      were similar between black patients and non-black patients, except for optic
      nerve sheath fenestration (p = 0.01) and lumbar puncture (p = 0.03), both more
      commonly performed on black patients. The relative risk of severe visual loss for
      black patients compared with non-black patients was 3.5 (95% CI 2.0 to 5.8, p <
      0.001) in at least one eye and 4.8 (95% CI 2.1 to 10.9, p < 0.001) in both eyes.
      Logistic regression analysis supported race, anemia, body mass index, and male
      gender as independent risk factors for severe visual loss and suggested that
      racial differences may be partially accounted for by differences in CSF opening
      pressure, body mass index, and frequency of anemia. CONCLUSION: Black patients
      with idiopathic intracranial hypertension (IIH) were more likely than non-black
      patients with IIH to have severe visual loss in at least one eye. This difference
      did not appear to result from diagnosis, treatment, or access to care, but may
      partially relate to differences in other risk factors. Black patients have a more
      aggressive disease and may need closer follow-up and lower thresholds for early
      intervention.

PMID- 18332345
TI  - Investigating genotype-phenotype relationships in Rett syndrome using an
      international data set.
AB  - BACKGROUND: Rett syndrome is an uncommon neurodevelopmental disorder with an
      incidence of 1:9,000 live female births. The principal genetic cause was first
      reported in 1999 when the association with mutations in the methyl-CpG-binding
      protein 2 (or MECP2) gene was identified. This study uses data from a large
      international database, InterRett, to examine genotype-phenotype relationships
      and compares these with previous findings in a population-based cohort. METHOD:
      The data set for these analyses was derived from a subset of InterRett cases with
      subject information collected from the family, the clinician, or both. Individual
      phenotypic characteristics and clinical severity using three scales were compared
      among those with eight known recurrent pathogenic MECP2 mutations as well as
      those with C-terminal deletions (n = 272). RESULTS: Overall, p.R270X and p.R255X
      were the most severe and p.R133C and p.R294X were the mildest mutations.
      Significant differences by mutation were seen for individual phenotypic
      characteristics such as hand use, ambulation, and language. CONCLUSIONS: This
      multicenter investigation into the phenotypic correlates of MECP2 mutations in
      Rett syndrome has provided a greater depth of understanding than hitherto
      available about the specific phenotypic characteristics associated with commonly
      occurring mutations. Although the modifying influence of X inactivation on
      clinical severity could not be included in the analysis, the findings confirm
      clear genotype-phenotype relationships in Rett syndrome and show the benefits of
      collaboration crucial to effective research in rare disorders.

PMID- 18332346
TI  - Invited article: Neurology education research.
AB  - BACKGROUND: There is a need to rigorously study the neurologic education of
      medical students, neurology residents, and neurologists to determine the
      effectiveness of our educational efforts. METHODS: We review the status of
      neurologic education research as it pertains to the groups of interest. RESULTS:
      We identify opportunities and impediments for education research. The
      introduction of the Accreditation Council for Graduate Medical Education core
      competencies, the Accreditation Council of Continuing Medical Education
      requirement to link continuing medical education to improved physician behavior
      and patient care, and the American Board of Medical Specialties/American Board of
      Psychiatry and Neurology-mandated maintenance of certification program represent
      research opportunities. Challenges include numerous methodologic issues such as
      definition of the theoretical framework of the study, adequate sample size
      ascertainment, and securing research funding. CONCLUSIONS: State-of-the-art
      education research will require multidisciplinary research teams and innovative
      funding strategies. The central goal of all concerned should be defining
      educational efforts that improve patient outcomes.

PMID- 18332347
TI  - Sporadic fatal insomnia in a fatal familial insomnia pedigree.

PMID- 18332348
TI  - Suprascapular nerve entrapment by a spinoglenoid cyst.

PMID- 18332349
TI  - Right brain: reading, writing, and reflecting: making a case for narrative
      medicine in neurology.

PMID- 18332350
TI  - Does NSAID use modify cognitive trajectories in the elderly? The cache county
      study.

PMID- 18332351
TI  - Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to
      chromosome 9q new evidence for a genetic link between epilepsy and migraine.

PMID- 18332352
TI  - Editorial: Gratitude and new beginnings.

PMID- 18332353
TI  - Spiritual care perspectives of Danish registered nurses.
AB  - A Gadamerian hermeneutic phenomenological methodology was selected to explicate
      the essence of spiritual care with six registered nurses working within hospital
      settings. Findings revealed that deep knowing of the patient was essential before
      registered nurses would engage in spiritual care. Furthermore, spirituality was
      understood as a private matter, with chaplains being seen as the most appropriate
      providers of such care. These findings suggest that within the culture of Danish
      nursing, a mandate to incorporate spiritual care into everyday nursing practice
      may be somewhat problematic.

PMID- 18332354
TI  - Commentary on "Spiritual care perspectives of Danish registered nurses":
      spiritual care as nursing care.

PMID- 18332355
TI  - The internal process of therapeutic touch.
AB  - Therapeutic Touch (TT) is a complementary healing modality used by health care
      providers to reduce anxiety, accelerate relaxation, decrease pain, and enhance
      immunity. Research studies report outcomes of TT treatments, but few describe the
      specific process. This qualitative research study was conducted to describe the
      nature of the core process of TT in adults and full term infants as practiced by
      five professional nurses, each treating one adult and one infant. Analysis of
      data obtained from interviews and focused participant observations was conducted.
      Findings provide empirical data to depict an overall process divided into three
      phases: (a) preparation, (b) treatment, and (c) termination, that adheres to the
      standard process as described by Krieger. It expands on the description of each
      phase, including two new subcomponents, orienting and disengagement, not
      previously seen in the literature. Lastly, the study describes the modification
      of the TT process with infants compared to adults.

PMID- 18332356
TI  - Commentary on "The internal process of therapeutic touch".

PMID- 18332357
TI  - Herb and supplement use among the retail population of an independent, urban herb
      store.
AB  - The prevalence of herbal medicine use among American adults is well documented.
      Because of the possible herb-drug interactions, health care providers need to be
      aware of herb and supplement use by their patients. This descriptive pilot study
      (N = 35) was designed to explore the demographics, beliefs, concurrent
      pharmaceutical use with herbs and supplements and their primary sources of
      information, and reporting of use to health care providers by customers at a
      retail specialty "herb" store. Results revealed that 62.5% of study participants
      who used herbs regularly also used pharmaceuticals. Among those who used herbs
      and supplements with pharmaceuticals, only 33% reported that they "always" tell
      their care provider about them. Forty-one percent reported that they receive most
      of their information about herbs and supplements from retail staff, but only 3%
      of participants reported that their primary source of information was a doctor,
      nurse, or pharmacist. Findings provide direction for future study.

PMID- 18332358
TI  - Commentary on "Herb and supplement use among the retail population of an
      independent, urban herb store".

PMID- 18332360
TI  - The influence of positive experiences on depression and quality of life in
      persons with multiple sclerosis.
AB  - PURPOSE: This correlational study determined the extent to which positive, rather
      than negative, experiences influence depressive symptoms and quality of life in
      persons with multiple sclerosis (MS). METHOD: Data collected during the 7th year
      of an ongoing longitudinal study of quality of life in community-dwelling persons
      with MS were used for this analysis. FINDINGS: Higher number of positive
      experiences was associated with fewer depressive symptoms, less functional
      limitations, and better quality of life. Using hierarchical multiple regression,
      age, education, functional limitations, and positive experiences accounted for
      21.7% of the variance in depressive symptoms, and functional limitations,
      positive experiences, and depressive symptoms explained 58% of the variance in
      quality of life. CONCLUSIONS: Higher number of positive experiences predicted
      lower levels of depressive symptoms, even while taking disease-related functional
      limitations into account. Incorporating positive experiences into daily life may
      improve quality of life, even when battling depression and substantial
      limitations in functioning.

PMID- 18332361
TI  - Commentary on "The influence of positive experiences on depression and quality of
      life in persons with multiple sclerosis".

PMID- 18332362
TI  - The use of puppetry for health promotion and suicide prevention among Mi'Kmaq
      youth.
AB  - PURPOSE: North American aboriginal youth have been shown to exhibit some of the
      highest suicide rates in the world. In this article, the authors examine the main
      factors related to suicide among aboriginal youth and ways to redress what many
      consider the most important factor. MAIN FACTOR: While many factors contribute to
      suicide plans, the literature would suggest "discontinuity" with heritage to have
      a particularly negative impact that needs priority redress. STRATEGY: A group of
      Mi'Kmaq elders and an interdisciplinary group of academicians blended traditional
      Mi'Kmaq knowledge and Western Science knowledge to develop a strategy to address
      such discontinuity. It involved using puppets made from natural forest materials
      to promote culture, language, and history. This article describes the strategy,
      its rationale, as well as its relevance for, and application to, holistic
      nursing.

PMID- 18332363
TI  - FEMA nurses face "Mission Impossible": remembering Katrina.
AB  - Dowd, a faculty member, is a strong proponent for nurses sharing their stories.
      Miller's story about her volunteer experience was so compelling that Dowd
      challenged her to share it with the nursing community. This story is a
      demonstration of how a nurse can bring leadership, sensitive interpersonal
      skills, and a sense of humor to help forge a cohesive and outward looking
      temporary community. Nurses naturally interact from a paradigm of care and
      comfort. Miller makes this interaction explicit. The outcome of the journey was a
      memorable lived experience that brought caring, healing, and comfort to a
      situation of devastation. It is hoped this nursing story will inspire the reader
      to try a similar new role or to tell their story.

PMID- 18332364
TI  - Distinguishing nursing art: patient, researcher, and student views. Associate
      editor introduction.

PMID- 18332365
TI  - Distinguishing nursing art: patient, researcher, and student views. Section
      introduction.

PMID- 18332366
TI  - Frances's story of nursing art: The most wonderful person in the world.
AB  - This story is the second in a series constructed from a study designed to
      describe how the art of nursing was perceived and understood by patients during a
      critical illness. Two in-depth interviews were conducted during the recovery
      phase of this person's illness to answer the question "When is nursing
      (considered) art?" The initial lead-in to the discussion was, "Tell me a story
      about a nursing situation that really stood out in your mind-one that was
      significant and meaningful," and, "What was the experience like for you?" The
      interviews were tape recorded, transcribed, condensed into a short story, and
      shared with the participant. The researcher also composed a "response" to the
      person's story that personally expressed what the story triggered for her.
      Undergraduate students were invited to reflect and respond to the "aesthetic
      face" of nursing from the perspective of a person who was nursed while critically
      ill. Two examples of student response are included.

PMID- 18332367
TI  - Nurse: technician and artist. "Frances's story": student response.
AB  - In this response to research reported by Dr. Gramling, the author of this
      response likens the art of nursing to a masterpiece drawn with the inner talents
      and gifts of nurses. Frances, a patient interviewed by Dr. Gramling, explains her
      experience of being carefully watched and feeling safe when a nurse pays close
      attention to her. The author has learned to define the art of nursing through the
      abstract concepts of the fine arts and asserts that the line between technician
      and artist is blurred. The poem written by Dr. Gramling in response to Frances
      reinforces the author's reading of how nursing becomes art.

PMID- 18332368
TI  - Nursing is an art. "Frances's story": student response.
AB  - In this response to research, the author likens the art of nursing to a work of
      art: abstract with blurred lines but lots of opportunity for interpretation.
      Frances, a patient interviewed by Dr. Kathryn Gramling as part of her research
      into patients' perception of nursing care, along with her family, felt comforted
      by her nurse, who devoted some of his own time to ensuring that Frances
      understood the procedure she needed and spent time meeting her need for human
      contact. The author experienced something similar during a hospital stay: She too
      had a nurse who spent time and gave comfort. The result is that the author
      understands the art of nursing as it relates to an extra effort to be human and
      demonstrate empathy. The poem written by Dr. Gramling in response to Frances
      confirms the patient's view of the art of nursing.

PMID- 18332371
TI  - Frank's story of nursing art: Ask me who I am.
AB  - This patient's story was constructed from a study designed to describe how the
      art of nursing was perceived and understood by patients during a critical
      illness. Two in-depth interviews were conducted during the recovery phase of this
      person's illness to answer the question "When is nursing (considered) art?" The
      initial lead-in to the discussion was, "Tell me a story about a nursing situation
      that really stood out in your mind--one that was significant and meaningful." The
      interviews were tape recorded, transcribed, condensed into a short story, and
      shared with the participant. The researcher, also, composed a response to the
      person's story that personally expressed what the story triggered for her.
      Undergraduate nursing students were invited to reflect and respond to the
      "aesthetic face" of nursing from the perspective of a person who was nursed while
      critically ill. An example of a student response is included.

PMID- 18332370
TI  - "Justine's story" and the art of nursing.
AB  - The author of this response to Dr. Kathryn Gramling's research on the art of
      nursing as perceived by patients agrees with patient Justine's assessment of the
      art. The author believes that the expression of a nurse's personality during the
      caring process creates the art. Justine saw all her nurses, even the brusque one,
      as performing in a caring way, each according to his/her own personality. The
      author believes this definition of the art of nursing is valid.

PMID- 18332375
TI  - A knee in the neck of excited delirium.

PMID- 18332378
TI  - Soup truck.

PMID- 18332377
TI  - More bang for the taxpayer's buck.

PMID- 18332372
TI  - The art of nursing. "Frank's story": student response.
AB  - The author of this article explores her definition of the art of nursing through
      a response to an interview by Dr. Kathryn Gramling with a patient named Frank.
      She determines that nursing, although it also requires technical skill and a
      strong knowledge base, becomes art when the practitioner adopts the caring skills
      of compassion, touching, and empathy. The poem Dr. Gramling wrote in response to
      her contact with Frank reinforces the definition created by the author. When some
      patients enter a hospital, they experience certain feelings, such as fear,
      uncertainty, and helplessness. They are placed in a strange setting and are not
      in the best of health, but each patient deals with sickness differently. Some may
      act frightened, while others may act impatient and uncooperative. Often, it is a
      nurse's duty to help ease a patient through this difficult transition. The way a
      nurse does this makes all the difference to a patient's stay at the hospital. A
      nurse's impact on the patient can affect the patient either positively or
      negatively. A nurse must go above and beyond the technical part of nursing in
      order to make nursing an art.

PMID- 18332369
TI  - Justine's story of nursing art: The presentation of nursing.
AB  - This patient's story was constructed from a study designed to describe how the
      art of nursing was perceived and understood by patients during a critical
      illness. Two in-depth interviews were conducted during the recovery phase of this
      person's illness to answer the question, "When is nursing (considered) art?" The
      initial lead-in to the discussion was, "Tell me a story about a nursing situation
      that really stood out in your mind--one that was significant and meaningful." The
      interviews were tape recorded, transcribed, condensed into a short story and
      shared with the participant. The researcher, also, composed a response to the
      person's story that personally expressed what the story triggered for her.
      Undergraduate nursing students were invited to reflect and respond to the
      "aesthetic face" of nursing from the perspective of a person who was nursed while
      critically ill. An example of a student response is included.

PMID- 18332376
TI  - US legislators drive accountability measures.

PMID- 18332381
TI  - Spontaneous hemothorax caused by metastasis of a rib tumour.

PMID- 18332374
TI  - Gutted programs and children's guts.

PMID- 18332380
TI  - Canadian cancer statistics at a glance: mesothelioma.

PMID- 18332382
TI  - Gastric acid burns because of a disconnected nasogastric tube.

PMID- 18332373
TI  - Ending the sexist blame game.

PMID- 18332386
TI  - Climate change and infectious diseases in North America: the road ahead.
AB  - Global climate change is inevitable--the combustion of fossil fuels has resulted
      in a buildup of greenhouse gases within the atmosphere, causing unprecedented
      changes to the earth's climate. The Fourth Assessment Report of the
      Intergovernmental Panel on Climate Change suggests that North America will
      experience marked changes in weather patterns in coming decades, including warmer
      temperatures and increased rainfall, summertime droughts and extreme weather
      events (e.g., tornadoes and hurricanes). Although these events may have direct
      consequences for health (e.g., injuries and displacement of populations due to
      thermal stress), they are also likely to cause important changes in the incidence
      and distribution of infectious diseases, including vector-borne and zoonotic
      diseases, water-and food-borne diseases and diseases with environmental
      reservoirs (e.g., endemic fungal diseases). Changes in weather patterns and
      ecosystems, and health consequences of climate change will probably be most
      severe in far northern regions (e.g., the Arctic). We provide an overview of the
      expected nature and direction of such changes, which pose current and future
      challenges to health care providers and public health agencies.

PMID- 18332387
TI  - In praise of undercover research.

PMID- 18332384
TI  - Joint contracture following prolonged stay in the intensive care unit.
AB  - BACKGROUND: Prolonged immobility during a critical illness may predispose
      patients to the development of joint contracture. We sought to document the
      incidence of, the risk factors for and the reversibility of joint contractures
      among patients who stayed in a tertiary intensive care unit (ICU) for 2 weeks or
      longer. METHODS: We conducted a chart review to collect data on the presence of
      and risk factors for joint contractures in the shoulders, elbows, hips, knees and
      ankles among patients admitted to the ICU between January 2003 and March 2005.
      RESULTS: At the time of transfer out of the ICU, at least 1 joint contracture was
      recorded in 61 (39%) of 155 patients; 52 (34%) of the patients had joint
      contractures of an extent documented to impair function. Time spent in the ICU
      was a significant risk factor for contracture: a stay of 8 weeks or longer was
      associated with a significantly greater risk of any joint contracture than a stay
      of 2 to 3 weeks (adjusted odds ratio [OR] 7.09, 95% confidence interval (CI) 1.29
      38.9; p = 0.02). Among the variables tested, only the use of steroids conferred a
      protective effect against joint contractures (adjusted OR 0.35, 95% CI 0.14-0.83;
      p = 0.02). At the time of discharge to home, which occurred a median of 6.6 weeks
      after transfer out of intensive care, 50 (34%) of the 147 patients not lost to
      follow-up still had 1 or more joint contractures, and 34 (23%) of the patients
      had at least 1 functionally significant joint contracture. INTERPRETATION:
      Following a prolonged stay in the ICU, a functionally significant contracture of
      a major joint occurred in more than one-third of patients, and most of these
      contractures persisted until the time of discharge to home.

PMID- 18332383
TI  - The effect of patients' sex on physicians' recommendations for total knee
      arthroplasty.
AB  - BACKGROUND: The underuse of total joint arthroplasty in appropriate candidates is
      more than 3 times greater among women than among men. When surveyed, physicians
      report that the patient's sex has no effect on their decision-making; however,
      what occurs in clinical practice may be different. The purpose of our study was
      to determine whether patients' sex affects physicians' decisions to refer a
      patient for, or to perform, total knee arthroplasty. METHODS: Seventy-one
      physicians (38 family physicians and 33 orthopedic surgeons) in Ontario performed
      blinded assessments of 2 standardized patients (1 man and 1 woman) with moderate
      knee osteoarthritis who differed only by sex. The standardized patients recorded
      the physicians' final recommendations about total knee arthroplasty. Four
      surgeons did not consent to the inclusion of their data. After detecting an
      overall main effect, we tested for an interaction with physician type (family
      physician v. orthopedic surgeon). We used a binary logistic regression analysis
      with a generalized estimating equation approach to assess the effect of patients'
      sex on physicians' recommendations for total knee arthroplasty. RESULTS: In
      total, 42% of physicians recommended total knee arthroplasty to the male but not
      the female standardized patient, and 8% of physicians recommended total knee
      arthroplasty to the female but not the male standardized patient (odds ratio [OR]
      4.2, 95% confidence interval [CI] 2.4-7.3, p < 0.001; risk ratio [RR] 2.1, 95% CI
      1.5-2.8, p < 0.001). The odds of an orthopedic surgeon recommending total knee
      arthroplasty to a male patient was 22 times (95% CI 6.4-76.0, p < 0.001) that for
      a female patient. The odds of a family physician recommending total knee
      arthroplasty to a male patient was 2 times (95% CI 1.04-4.71, p = 0.04) that for
      a female patient. INTERPRETATION: Physicians were more likely to recommend total
      knee arthroplasty to a male patient than to a female patient, suggesting that
      gender bias may contribute to the sex-based disparity in the rates of use of
      total knee arthroplasty.

PMID- 18332389
TI  - How useful is uterine artery Doppler ultrasonography in predicting pre-eclampsia
      and intrauterine growth restriction?

PMID- 18332388
TI  - Mobile, awake and critically ill.

PMID- 18332390
TI  - Krever: the recommendation not followed.

PMID- 18332391
TI  - Hunger in Canada.

PMID- 18332392
TI  - Information about a discontinued drug.

PMID- 18332385
TI  - Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and
      intrauterine growth restriction: a systematic review and bivariable meta
      analysis.
AB  - BACKGROUND: Alterations in waveforms in the uterine artery are associated with
      the development of pre-eclampsia and intrauterine growth restriction. We
      investigated the predictive accuracy of all uterine artery Doppler indices for
      both conditions in the first and second trimesters. METHODS: We identified
      relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and
      Medion databases (all records to April 2006) and by checking bibliographies of
      identified studies and consulting with experts. Four of us independently selected
      studies, extracted data and assessed study validity. We performed a bivariable
      meta-analysis of sensitivity and specificity and calculated likelihood ratios.
      RESULTS: We identified 74 studies of pre-eclampsia (total 79,547 patients) and 61
      studies of intrauterine growth restriction (total 41 131 patients). Uterine
      artery Doppler ultrasonography provided a more accurate prediction when performed
      in the second trimester than in the first-trimester. Most Doppler indices had
      poor predictive characteristics, but this varied with patient risk and outcome
      severity. An increased pulsatility index with notching was the best predictor of
      pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5
      among low-risk patients). It was also the best predictor of overall (positive
      likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine
      growth restriction among low-risk patients. INTERPRETATION: Abnormal uterine
      artery waveforms are a better predictor of pre-eclampsia than of intrauterine
      growth restriction. A pulsatility index, alone or combined with notching, is the
      most predictive Doppler index. These indices should be used in clinical practice.
      Future research should also concentrate on combining uterine artery Doppler
      ultrasonography with other tests.

PMID- 18332394
TI  - Colorectal cancer screening.

PMID- 18332398
TI  - No gender influences on clinical outcomes or durability of repair following
      carotid angioplasty with stenting and carotid endarterectomy.
AB  - INTRODUCTION: To determine if gender influences clinical outcomes and durability
      of repair after carotid angioplasty with stenting (CAS) or carotid endarterectomy
      (CEA), an analysis of patient records was performed. METHODS: This study included
      89 CAS patients (47 men and 42 women) and 93 CEA patients (53 men and 40 women).
      Patients underwent duplex scans 6, 12, 24 months post procedure. The outcomes of
      periprocedural mortality, major adverse events, strokes, and myocardial
      infarctions were assessed. Incidence of critical restenosis and recurrence of
      symptoms was also assessed. RESULTS: No significant differences were noted
      between men and women who had undergone either CAS or CEA (P > .05) for clinical
      outcomes and durability of repair. No differences for periprocedural mortality,
      major adverse events, critical restenosis, recurrent neurologic symptoms, and
      adverse event free survival were found. CONCLUSIONS: These results do not
      indicate substantial gender influences on clinical outcomes or durability of
      repair following CAS and CEA.

PMID- 18332395
TI  - Fiction dereliction.

PMID- 18332399
TI  - Prognostic factors and treatment outcome in mesenteric vein thrombosis.
AB  - BACKGROUND: Mesenteric vein thrombosis (MVT) can result in intestinal ischemia
      and is associated with high morbidity and mortality due in part to its frequent
      delay in diagnosis. The purpose of this study was to evaluate clinical
      presentation, diagnostic evaluation, and treatment outcome of MVT. METHODS:
      Hospital records and clinical data of all patients treated for MVT were reviewed
      during a recent 14-year period. Clinical outcome and factors affecting survival
      were analyzed. RESULTS: A total of 68 patients were included in the study.
      Abdominal exploration was performed in 23 patients (34%), and second-look
      operation was necessary in 18 patients (26%). Three patients (4%) underwent
      unsuccessful operative mesenteric vein thrombectomy, whereas percutaneous
      transhepatic mesenteric thrombectomy was performed successfully in 3 patients
      (4%). The 30-day mortality rate was 20%. Forty-six of the 54 survivors were
      treated with long-term oral anticoagulation therapy. Actuarial survival at 2, 4,
      6, and 10 years was 68%, 57%, 43%, and 22%, respectively. Risk factor analysis
      showed malignancy (P < .002), age >60 years (P < .005), cirrhosis (P < .02),
      symptom duration (P < .005), and bowel resection (P < .03) were associated with
      mortality. Logistic regression analysis showed age >60 years (odds ratio [OR],
      3.64; P = .03), malignancy (OR, 3.88; P = .02), and prolonged symptom duration
      (OR, 5.62; P = .01) were independent predictors of mortality. CONCLUSIONS: MVT is
      associated with significant mortality. Prompt diagnostic evaluation with computed
      tomography may reduce potential treatment delay. Underlying malignancy, advanced
      age, and prolonged symptom duration are predictive of poor outcome.

PMID- 18332397
TI  - Characterization of activities of daily living in individuals with mild cognitive
      impairment.
AB  - OBJECTIVE: To determine whether participants with mild cognitive impairment (MCI)
      differ from cognitively normal (NC) older adults on traditional and novel
      informant-based measures of activities of daily living (ADL) and to identify
      cognitive correlates of ADLs among participants with MCI. DESIGN: Cross
      sectional. SETTING: University medical setting. PARTICIPANTS: Seventy-seven
      participants (NC: N = 39; MCI: N = 38), 60 to 90 years old (73.5 +/- 6.6 years;
      53% female). MEASUREMENTS: Neuropsychological and ADL measures. METHODS:
      Neuropsychological tests were administered to NC and MCI participants. Informants
      completed the Lawton and Brody Instrumental Activities of Daily Living and
      Physical Self-Maintenance Scale, including instrumental (IADL) and basic ADL
      (BADL) scales, as well as the Functional Capacities for Activities of Daily
      Living (FC-ADL), an error-based ADL measure. RESULTS: No statistically or
      clinically significant between-group differences emerged for the BADL or IADL
      subscales. However, a robust difference was noted for the FC-ADL scale (MCI
      errors > NC errors; F((1,75))= 13.6, p <0.001; d = 0.84). Among MCI participants,
      correlations revealed that a measure of verbal learning was the only
      neuropsychological correlate of FC-ADL total score (r = -0.39, df = 36, p =
      0.007). No neuropsychological measures were significantly associated with the
      IADL or BADL subscale score. CONCLUSION: Traditional measures assessing global
      ADLs may not be sensitive to early functional changes related to MCI; however,
      error-based measures may capture the subtle evolving functional decline
      associated with MCI. Among MCI participants, early functional difficulties are
      associated with verbal learning performance, possibly secondary to the hallmark
      cognitive impairment associated with this cohort.

PMID- 18332400
TI  - Catheter-directed thrombolysis for acute renal artery thrombosis: report of 4
      cases.
AB  - Acute renal artery occlusion is a rare but threatening problem; optimal
      therapeutic treatment remains a challenge, and ultimate outcomes are still to be
      defined. In the last decades, several reports or short-case experiences have been
      reported describing the use of selective infusion of lytic agents into renal
      artery to treat acute occlusion. We report 4 cases of acute renal artery
      occlusion treated by catheter-directed intraarterial thrombolysis.

PMID- 18332403
TI  - Practice features associated with patient-reported accessibility, continuity, and
      coordination of primary health care.
AB  - PURPOSE: On the eve of major primary health care reforms, we conducted a
      multilevel survey of primary health care clinics to identify attributes of clinic
      organization and physician practice that predict accessibility, continuity, and
      coordination of care as experienced by patients. METHODS: Primary health care
      clinics were selected by stratified random sampling in urban, suburban, rural,
      and remote locations in Quebec, Canada. Up to 4 family or general physicians were
      selected in each clinic, and 20 patients seeing each physician used the Primary
      Care Assessment Tool to report on first-contact accessibility (being able to
      obtain care promptly for sudden illness), relational continuity (having an
      ongoing relationship with a physician who knew their particulars), and
      coordination continuity (having coordination between their physician and
      specialists). Physicians reported on aspects of their practice, and secretaries
      and directors reported on organizational features of the clinic. We used
      hierarchical regression modeling on the subsample of regular patients at the
      clinic. RESULTS: One hundred clinics participated (61% response rate), for a
      total of 221 physicians and 2,725 regular patients (87% response and completion
      rate). First-contact accessibility was most problematic. Such accessibility was
      better in clinics with 10 or fewer physicians, a nurse, telephone access 24 hours
      a day and 7 days a week, operational agreements to facilitate care with other
      health care establishments, and evening walk-in services. Operational agreements
      and evening care also positively affected relational continuity. Physicians who
      valued continuity and felt attached to the community fostered better relational
      continuity, whereas an accessibility-oriented style (as indicated by a high
      proportion of walk-in care and high patient volume) hindered it. Coordination
      continuity was also associated with more operational agreements and continuous
      telephone access, and was better when physicians practiced part time in hospitals
      and performed a larger range of medical procedures in their office. CONCLUSIONS:
      The way a clinic is organized allows physicians to achieve both accessibility and
      continuity rather than one or the other. Features that achieve both are offering
      care in the evenings and access to telephone advice, and having operational
      agreements with other health care establishments.

PMID- 18332404
TI  - Bypass of local primary care in rural counties: effect of patient and community
      characteristics.
AB  - PURPOSE: This national study sought information from rural patients (1) to assess
      the prevalence of bypass, a pattern of seeking health care outside the local
      community; (2) to examine the impact of locally available primary care physicians
      (PCPs) and hospital size on the odds of bypass; and (3) to identify patient
      demographic and geographic factors associated with bypass. This study also
      ascertained the reasons patients give for bypass and their suggestions for how
      hospitals can retain patients locally. METHODS: We analyzed data from a 2005
      telephone survey of 1,264 adults, aged 18 years or older, who lived within 20
      miles of 25 randomly selected Critical Access Hospitals and were linked with a
      Health Professional Shortage Area and 2004 census data. Respondents were asked
      about demographic characteristics, travel time and distance to local hospitals,
      and insurance status, as well as for suggestions of what local hospitals could do
      to retain patients. RESULTS: Overall, 32% of respondents bypassed local primary
      care; the rate ranged from 9% to 66% across the Critical Access Hospital service
      areas. Factors associated with bypass included age, education, marital status,
      satisfaction with the local hospital, admission to a hospital in the past 12
      months, hospital size, and local density of PCPs. Compared with residents in
      areas with a higher density of PCPs (=3,500 residents per PCP), residents in
      areas with a low density (>4,500 residents per PCP) were more likely to bypass
      local care (odds ratio, 1.58; 95% confidence interval, 1.02-2.46). Lack of
      specialty care and limited services were most frequently mentioned as reasons why
      patients bypassed local hospitals. CONCLUSIONS: The sizable variation in bypass
      rates among this sample of Critical Access Hospital service areas suggests that
      strategies to reduce bypass behavior should be directed at the local community or
      facility level. Changing rural residents' perception of their local care, helping
      them gain a better understanding of the function of primary care, and increasing
      the number of PCPs might help hospitals retain patients and rural communities
      stay healthy.

PMID- 18332402
TI  - What patients want from primary care consultations: a discrete choice experiment
      to identify patients' priorities.
AB  - PURPOSE: The consultation is fundamental to the delivery of primary care, but
      different ways of organizing consultations may lead to different patient
      experiences in terms of access, continuity, technical quality of care, and
      communication. Patients' priorities for these different issues need to be
      understood, but the optimal methods for assessing priorities are unclear. This
      study used a discrete choice experiment to assess patients' priorities. METHODS:
      We surveyed patients from 6 family practices in England. The patients chose
      between primary care consultations differing in attributes such as ease of access
      (wait for an appointment), choice (flexibility of appointment times), continuity
      (physician's knowledge of the patient), technical quality (thoroughness of
      physical examination), and multiple aspects of patient-centered care (interest in
      patient's ideas, inquiry about patient's social and emotional well-being, and
      involvement of patient in decision making). We used probit models to assess the
      relative priority patients placed on different attributes and to estimate how
      much they were willing to pay for them. RESULTS: Analyses were based on responses
      from 1,193 patients (a 53% response rate). Overall, patients were willing to pay
      the most for a thorough physical examination ($40.87). The next most valued
      attributes of care were seeing a physician who knew them well ($12.18), seeing a
      physician with a friendly manner ($8.50), having a reduction in waiting time of 1
      day ($7.22), and having flexibility of appointment times ($6.71). Patients placed
      similar value on the different aspects of patient-centered care ($12.06-$14.82).
      Responses were influenced by the scenario in which the decision was made (minor
      physical problem vs urgent physical problem vs ambiguous physical or
      psychological problem) and by patients' demographic characteristics. CONCLUSIONS:
      Although patient-centered care is important to patients, they may place higher
      priority on the technical quality of care and continuity of care. Discrete choice
      experiments may be a useful method for assessing patients' priorities in health
      care.

PMID- 18332401
TI  - Effect of psyllium fiber supplementation on C-reactive protein: the trial to
      reduce inflammatory markers (TRIM).
AB  - PURPOSE: Recent evidence supports a significant association between the intake of
      dietary fiber and levels of inflammatory markers. The objective of this study was
      to determine whether daily fiber supplementation would reduce levels of
      inflammatory markers. METHODS: This study was a prospective randomized controlled
      trial at a single university medical center. Participants were overweight or
      obese adults with no history of heart disease. The intervention was psyllium
      supplementation at either 7 or 14 g/d for 3 months compared with no supplements
      in a control group. The main outcome measure was change in level of high
      sensitivity C-reactive protein (hsCRP) concentration; secondary outcomes included
      changes in interleukin-6 (IL-6) levels, fibrinogen levels, and white blood cell
      (WBC) count. Protocol completers attended at least 2 visits and took more than
      75% of the prescribed fiber dose. RESULTS: In this intent-to-treat analysis (n =
      158), there were no significant differences between either of the 2 treatment
      groups and the control group in the amount of change in CRP, fibrinogen, or IL-6
      levels or in WBC count (P>.05). In the analysis of protocol completers (n = 132),
      there also were no significant differences between the groups except for a small
      decrease in fibrinogen level in the high-fiber group (-6 mg/dL [-0.18 micromol/L]
      compared with 13 mg/dL [0.38 micromol/L] in the control group, P<.05).
      CONCLUSION: Psyllium fiber supplementation did not significantly reduce CRP
      levels in overweight or obese individuals in this trial, and changes in other
      markers were not consistent. Further research is needed to determine whether
      other fibers or nutrients can reduce inflammatory markers.

PMID- 18332406
TI  - Balint groups as a means to increase job satisfaction and prevent burnout among
      general practitioners.
AB  - PURPOSE: General practitioners (GPs) occupy a central position in health care and
      often have demanding working situations. This corps shows signs of exhaustion,
      and many consider quitting their job or plan to retire early. It is therefore
      urgent to find ways of improving GP's satisfaction with their work. One approach
      might be Balint group participation. The aim of this study was to explore GPs'
      experience of participating in Balint groups and its influence on their work
      life. METHODS: We conducted a descriptive, qualitative study. Nine GPs who had
      participated in Balint groups for 3 to 15 years were interviewed. A
      phenomenologic analysis was carried out to describe the phenomenon of Balint
      group participation. RESULTS: The GPs perceived that their Balint group
      participation influenced their work life. Analyses revealed several interrelating
      themes: competence, professional identity, and a sense of security, which
      increased through parallel processes, creating a base of endurance and
      satisfaction, thus enabling the GPs to rediscover the joy of being a physician.
      CONCLUSIONS: The GPs in this study described their Balint group participation as
      beneficial and essential to their work life as physicians in several ways. It
      seemed to increase their competence in patient encounters and enabled them to
      endure in their job and find joy and challenge in their relationships with
      patients. Balint groups might thus help GPs handle a demanding work life and
      prevent burnout. These groups might not suit all GPs, however, and additional
      ways to reduce stress and increase job satisfaction should be offered.

PMID- 18332408
TI  - Data collection outcomes comparing paper forms with PDA forms in an office-based
      patient survey.
AB  - PURPOSE: We compared the completeness of data collection using paper forms and
      using electronic forms loaded on handheld computers in an office-based patient
      interview survey conducted within the American Academy of Family Physicians
      National Research Network. METHODS: We asked 19 medical assistants and nurses in
      family practices to administer a survey about pneumococcal immunizations to 60
      older adults each, 30 using paper forms and 30 using electronic forms on handheld
      computers. By random assignment, the interviewers used either the paper or
      electronic form first. Using multilevel analyses adjusted for patient
      characteristics and clustering of forms by practice, we analyzed the completeness
      of the data. RESULTS: A total of 1,003 of the expected 1,140 forms were returned
      to the data center. The overall return rate was better for paper forms (537 of
      570, 94%) than for electronic forms (466 of 570, 82%) because of technical
      difficulties experienced with electronic data collection and stolen or lost
      handheld computers. Errors of omission on the returned forms, however, were more
      common using paper forms. Of the returned forms, only 3% of those gathered
      electronically had errors of omission, compared with 35% of those gathered on
      paper. Similarly, only 0.04% of total survey items were missing on the electronic
      forms, compared with 3.5% of the survey items using paper forms. CONCLUSIONS:
      Although handheld computers produced more complete data than the paper method for
      the returned forms, they were not superior because of the large amount of missing
      data due to technical difficulties with the hand-held computers or loss or theft.
      Other hardware solutions, such as tablet computers or cell phones linked via a
      wireless network directly to a Web site, may be better electronic solutions for
      the future.

PMID- 18332407
TI  - Beyond fighting fires and chasing tails? Chronic illness care plans in Ontario,
      Canada.
AB  - PURPOSE: Recent work has conceptualized new models for the primary care
      management of patients with chronic illness. This study investigated the
      experience of family physicians and patients with a chronic illness management
      initiative that involved the joint formulation of comprehensive individual
      patient care plans. METHODS: A qualitative evaluation, framed by phenomenology,
      immediately followed a randomized controlled trial examining the effect of
      external facilitators in enhancing the delivery of chronic condition care
      planning in primary care. The study, set in Ontario family practices, used
      semistructured in-depth interviews with a purposive sample of 13 family
      physicians, 20 patients, and all 3 study facilitators. Analysis used independent
      transcript review and constant comparative methods. RESULTS: Despite the
      intervention being grounded in patient-centered principles, family physicians
      generally viewed chronic illness management from a predominantly biomedical
      perspective. Only a few enthusiasts viewed systematic care planning as a new
      approach to managing patients with chronic illness. Most family physicians found
      the strategy to be difficult to implement within existing organizational and
      financial constraints. For these participants, care planning conflicted with
      preexisting concepts of their role and of their patient's abilities to become
      partners in care. The few patients who noticed the process spoke favorably about
      their experience. CONCLUSIONS: Although the experiences of the enthusiastic
      family physicians were encouraging, we found important individual-level barriers
      to chronic illness management in primary care. These issues seemed to transcend
      existing organizational and resource constraints.

PMID- 18332405
TI  - Acculturation and healthy lifestyle among Latinos with diabetes.
AB  - PURPOSE: Latinos have a high prevalence of diabetes and disproportionately
      experience diabetic complications. We sought to examine the association of
      acculturation on healthy lifestyle habits among the Latino population in the
      United States with diabetes. METHODS: We studied Latino adults (aged >or=20
      years) with previously diagnosed diabetes in the 1999-2004 National Health and
      Nutrition Examination Survey (unweighted N = 467; weighted N = 1,957,778).
      Healthy lifestyle habits were those consistent with recommendations of the
      American Diabetes Association (ADA) regarding exercise, smoking, obesity, and
      diet. Acculturation was measured with the Short Acculturation Scale, a validated
      5-item scale assessing use of the Spanish language. Logistic regression analyses
      of acculturation and healthy behaviors were computed controlling for access to
      care, demographics, and disease characteristics. RESULTS: In bivariate analyses,
      compared with their less-acculturated counterparts, individuals who were more
      acculturated to any extent were less likely to have a higher fiber intake (9.4%
      vs 35.4%, P = .001) and lower saturated fat intake (17.2% vs 46.5%, P = .03).
      More-acculturated individuals were more likely to report leisure time exercise
      (59.2% vs 19.3%, P <.001), whereas the proportion of individuals who smoked did
      not differ. In logistic regression analyses using the 1994 ADA dietary
      guidelines, more-acculturated individuals were less likely than their less
      acculturated counterparts to meet dietary criteria for saturated fat consumption
      (odds ratio, 0.13; 95% confidence interval [CI], 0.04-0.41). When using the
      stricter 2006 ADA dietary guidelines, more-acculturated individuals were less
      likely to have recommended consumption of both saturated fat (odds ratio, 0.06;
      95% CI, 0.02-0.20) and fiber (odds ratio, 0.19; 95% CI, 0.08-0.48). Acculturation
      did not significantly influence exercise and smoking status in logistic
      regression analyses. CONCLUSIONS: These results suggest that acculturation among
      diabetic Latinos to the general US culture is associated with adoption of some
      less desirable dietary habits.

PMID- 18332409
TI  - Narrative reports to monitor and evaluate the integration of pharmacists into
      family practice settings.
AB  - PURPOSE: Narratives can capture unfolding events and negotiation of roles and
      thus can help to evaluate interventions in interdisciplinary health care teams.
      We describe a practical qualitative method, the narrative report, and its role in
      evaluating implementation research. METHODS: We used narrative reports as a means
      to evaluate an intervention to integrate pharmacists into group family practices.
      The pharmacists submitted 63 written narrative reports during a 1-year period.
      Our interdisciplinary research team analyzed these reports to monitor the
      progress of the implementation, to identify pharmacists' needs, and to capture
      elements of the integration process. RESULTS: The monthly narrative reports
      allowed the research team to document early learning and calibrate the program in
      terms of clinical support, adapting roles, and realigning expectations. The
      reports helped the research team stay in tune with practice-related
      implementation challenges, and the preliminary summary of narrative findings
      provided a forum for sharing innovations among the integrating pharmacists.
      CONCLUSION: The narrative report can be a successful qualitative tool to track
      and evaluate the early stages of an intervention in the context of evolving
      primary health care teams.

PMID- 18332410
TI  - Screening for congenital hypothyroidism: US Preventive Services Task Force
      reaffirmation recommendation.

PMID- 18332411
TI  - Screening for phenylketonuria (PKU): US Preventive Services Task Force
      Reaffirmation recommendation.

PMID- 18332412
TI  - Changing horses midstream: the promise and prudence of practice redesign.
AB  - An emerging vision for primary care calls for the adoption of information
      technology and a strong business model to save a dying health care system. The
      authors are participants in the National Demonstration Project (NDP), a study
      sponsored by leading organizations in family medicine and directed by a for
      profit subsidiary of the American Academy of Family Physicians, TransforMED. The
      NDP embraces the Future of Family Medicine Report and seeks to test the ability
      of existing practices to implement its basic tenets. The NDP will conclude in
      June 2008, but its findings and observations will likely ripple out for years.
      Our report is a personal reflection that looks beyond the question of whether
      busy practices and practitioners can change horses midstream. We ask, "Is this
      primary care, and is this what it needs?"

PMID- 18332413
TI  - Success, regret, and the struggle for balance.
AB  - The genesis of this article was a conversation between the authors: M.I., a
      senior faculty member, and J.C., his primary care doctor and a midcareer faculty
      member. It addresses the challenges facing physicians today as they struggle to
      strike the proper balance between career and personal life; it also addresses the
      potential toll to oneself and loved ones when career success is placed above all
      other concerns.

PMID- 18332414
TI  - Healing with the needles.
AB  - A child's spontaneous desire to help her mother during an office visit prompts me
      to reflect upon the multidimensional nature of healing and how, as family
      physicians, we often encounter these unique moments in our day-to-day practice.

PMID- 18332415
TI  - Assembling patient-centered medical homes--the clerkship initiative.

PMID- 18332416
TI  - You have to be in to win: presenting family medicine's perspective in NIH
      scientific reviews.

PMID- 18332417
TI  - Title VII: revisiting an opportunity.

PMID- 18332418
TI  - CTSAs and family medicine research--time to get connected.

PMID- 18332419
TI  - AAFP continues to fight for payment reform.

PMID- 18332420
TI  - A new focus on research.

PMID- 18332421
TI  - Helicobacter pylori evolution during progression from chronic atrophic gastritis
      to gastric cancer and its impact on gastric stem cells.
AB  - We have characterized the adaptations of Helicobacter pylori to a rarely captured
      event in the evolution of its impact on host biology-the transition from chronic
      atrophic gastritis (ChAG) to gastric adenocarcinoma-and defined the impact of
      these adaptations on an intriguing but poorly characterized interaction between
      this bacterium and gastric epithelial stem cells. Bacterial isolates were
      obtained from a single human host colonized with a single dominant strain before
      and after his progression from ChAG to gastric adenocarcinoma during a 4-year
      interval. Draft genome assemblies were generated from two isolates, one ChAG
      associated, the other cancer-associated. The cancer-associated strain was less
      fit in a gnotobiotic transgenic mouse model of human ChAG and better able to
      establish itself within a mouse gastric epithelial progenitor-derived cell line
      (mGEP) that supports bacterial attachment. GeneChip-based comparisons of the
      transcriptomes of mGEPs and a control mouse gastric epithelial cell line revealed
      that, upon infection, the cancer-associated strain regulates expression of GEP
      associated signaling and metabolic pathways, and tumor suppressor genes
      associated with development of gastric cancer in humans, in a manner distinct
      from the ChAG-associated isolate. The effects on GEP metabolic pathways, some of
      which were confirmed in gnotobiotic mice, together with observed changes in the
      bacterial transcriptome are predicted to support aspects of an endosymbiosis
      between this microbe and gastric stem cells. These results provide insights about
      how H. pylori may adapt to and influence stem cell biology and how its
      intracellular residency could contribute to gastric tumorigenesis.

PMID- 18332422
TI  - Correctly folded Pfs48/45 protein of Plasmodium falciparum elicits malaria
      transmission-blocking immunity in mice.
AB  - Malaria kills >1 million people each year, in particular in sub-Saharan Africa.
      Although asexual forms are directly responsible for disease and death, sexual
      stages account for the transmission of Plasmodium parasites from human to the
      mosquito vector and therefore the spread of the parasite in the population.
      Development of a malaria vaccine is urgently needed to reduce morbidity and
      mortality. Vaccines against sexual stages of Plasmodium falciparum are meant to
      decrease the force of transmission and consequently reduce malaria burden.
      Pfs48/45 is specifically expressed in sexual stages and is a well established
      transmission-blocking (TB) vaccine candidate. However, production of correctly
      folded recombinant Pfs48/45 protein with display of its TB epitopes has been a
      major challenge. Here, we show the production of a properly folded Pfs48/45 C
      terminal fragment by simultaneous coexpression with four periplasmic folding
      catalysts in Escherichia coli. This C-terminal fragment fused to maltose binding
      protein was produced at medium scale with >90% purity and a stability over at
      least a 9-month period. It induces uniform and high antibody titers in mice and
      elicits functional TB antibodies in standard membrane feeding assays in 90% of
      the immunized mice. Our data provide a clear perspective on the clinical
      development of a Pfs48/45-based TB malaria vaccine.

PMID- 18332423
TI  - A disulfide-stabilized conformer of methionine synthase reveals an unexpected
      role for the histidine ligand of the cobalamin cofactor.
AB  - B(12)-dependent methionine synthase (MetH) from Escherichia coli is a large
      modular protein that is alternately methylated by methyltetrahydrofolate to form
      methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major
      domain rearrangements are required to allow cobalamin to react with three
      different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l
      methionine (AdoMet). These same rearrangements appear to preclude crystallization
      of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal
      fragment of the enzyme into a unique conformation. Cysteine point mutations were
      introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the
      cobalamin-binding module and form a cross-link that reduces the conformational
      space accessed by the enzyme, facilitating protein crystallization. Here, we
      describe an x-ray structure of the mutant fragment in the reactivation
      conformation; this conformation enables the transfer of a methyl group from
      AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the
      cobalamin, His-759, dissociates from the cobalamin and forms intermodular
      contacts with residues in the AdoMet-binding module. This unanticipated
      intermodular interaction is expected to play a major role in controlling the
      distribution of conformers required for the catalytic and the reactivation cycles
      of the enzyme.

PMID- 18332424
TI  - Aberrant early-phase ERK inactivation impedes neuronal function in fragile X
      syndrome.
AB  - Fragile X syndrome (FXS) has so far resisted efforts to define the basic cellular
      defects caused by the absence of a single protein, fragile X mental retardation
      protein (FMRP), because the patients have a wide variety of symptoms of varying
      severity. Immature-appearing dendritic spines on neurons found in FXS patients
      and fmr1-KO mice suggest a role for FMRP in modulating production of synaptic
      structural proteins. We isolated cortical synaptoneurosomes from WT and KO mice
      and studied MAPK pathway activation after group I metabotropic glutamate receptor
      (mGluR) stimulation. Here, we show that ERK in KO synaptoneurosomes is rapidly
      dephosphorylated upon mGluR1/5 stimulation, whereas it is phosphorylated in WT
      mice, suggesting that aberrant activation of phosphatases occurs in KO synapses
      in response to synaptic stimulation. In KO synapses, protein phosphatase 2A
      (PP2A) is overactivated after mGluR1 stimulation, and tyrosine phosphatase is
      overactivated after mGluR5 stimulation, causing the rapid deactivation of ERK.
      ERK activation can be restored in KO by pretreatment with phosphatase blockers;
      blocking of PP2A by okadaic acid could successfully restore normal ERK activation
      in KO synaptoneurosomes. We propose that overactivation of phosphatases in
      synapses may be a key deficit in FXS, which affects synaptic translation,
      transcription, and synaptic receptor regulation.

PMID- 18332425
TI  - Low-level viremia persists for at least 7 years in patients on suppressive
      antiretroviral therapy.
AB  - Residual viremia can be detected in most HIV-1-infected patients on
      antiretroviral therapy despite suppression of plasma RNA to <50 copies per ml,
      but the source and duration of this viremia is currently unknown. Therefore, we
      analyzed longitudinal plasma samples from 40 patients enrolled in the Abbott M97
      720 trial at baseline (pretherapy) and weeks 60 to 384 by using an HIV-1 RNA
      assay with single-copy sensitivity. All patients were on therapy
      (lopinavir/ritonavir, stavudine, and lamivudine) with plasma HIV RNA <50 copies
      per ml by week 96 of the study and thereafter. Single-copy assay results revealed
      that 77% of the patient samples had detectable low-level viremia (>/=1 copy per
      ml), and all patients had at least one sample with detectable viremia. A
      nonlinear mixed effects model revealed a biphasic decline in plasma RNA levels
      occurring over weeks 60 to 384: an initial phase of decay with a half-life of 39
      weeks and a subsequent phase with no perceptible decay. The level of pretherapy
      viremia extrapolated for each phase of decay was significantly correlated with
      total baseline viremia for each patient (R(2) = 0.27, P = 0.001 and R(2) = 0.19,
      P < 0.005, respectively), supporting a biological link between the extent of
      overall baseline viral infection and the infection of long-lived reservoirs.
      These data suggest that low-level persistent viremia appears to arise from at
      least two cell compartments, one in which viral production decays over time and a
      second in which viral production remains stable for at least 7 years.

PMID- 18332426
TI  - Intermittent recombinant TSH injections prevent ovariectomy-induced bone loss.
AB  - We recently described the direct effects of thyroid-stimulating hormone (TSH) on
      bone and suggested that the bone loss in hyperthyroidism, hitherto attributed
      solely to elevated thyroid hormone levels, could at least in part arise from
      accompanying decrements in serum TSH. Recent studies on both mice and human
      subjects provide compelling evidence that thyroid hormones and TSH have the
      opposite effects on the skeleton. Here, we show that TSH, when injected
      intermittently into rodents, even at intervals of 2 weeks, displays a powerful
      antiresorptive action in vivo. By virtue of this action, together with the
      possible anabolic effects shown earlier, TSH both prevents bone loss and restores
      the lost bone after ovariectomy. Importantly, the osteoclast inhibitory action of
      TSH persists ex vivo even after therapy is stopped for 4 weeks. This profound and
      lasting antiresorptive action of TSH is mimicked in cells that genetically
      overexpress the constitutively active ligand-independent TSH receptor (TSHR). In
      contrast, loss of function of a mutant TSHR (Pro --> Leu at 556) in congenital
      hypothyroid mice activates osteoclast differentiation, confirming once again our
      premise that TSHRs have a critical role in regulating bone remodeling.

PMID- 18332427
TI  - Optical measurement of synaptic glutamate spillover and reuptake by linker
      optimized glutamate-sensitive fluorescent reporters.
AB  - Genetically encoded sensors of glutamate concentration are based on FRET between
      cyan and yellow fluorescent proteins bracketing a bacterial glutamate-binding
      protein. Such sensors have yet to find quantitative applications in neurons,
      because of poor response amplitude in physiological buffers or when expressed on
      the neuronal cell surface. We have improved our glutamate-sensing fluorescent
      reporter (GluSnFR) by systematic optimization of linker sequences and glutamate
      affinities. Using SuperGluSnFR, which exhibits a 6.2-fold increase in response
      magnitude over the original GluSnFR, we demonstrate quantitative optical
      measurements of the time course of synaptic glutamate release, spillover, and
      reuptake in cultured hippocampal neurons with centisecond temporal and spine
      sized spatial resolution. During burst firing, functionally significant spillover
      persists for hundreds of milliseconds. These glutamate levels appear sufficient
      to prime NMDA receptors, potentially affecting dendritic spike initiation and
      computation. Stimulation frequency-dependent modulation of spillover suggests a
      mechanism for nonsynaptic neuronal communication.

PMID- 18332428
TI  - Acetylcholinesterase inhibitors and Gulf War illnesses.
AB  - Increasing evidence suggests excess illness in Persian Gulf War veterans (GWV)
      can be explained in part by exposure of GWV to organophosphate and carbamate
      acetylcholinesterase inhibitors (AChEis), including pyridostigmine bromide (PB),
      pesticides, and nerve agents. Evidence germane to the relation of AChEis to
      illness in GWV was assessed. Many epidemiological studies reported a link between
      AChEi exposure and chronic symptoms in GWV. The link is buttressed by a dose
      response relation of PB pill number to chronic symptoms in GWV and by a relation
      between avidity of AChEi clearance and illness, based on genotypes,
      concentrations, and activity levels of enzymes that detoxify AChEis.
      Triangulating evidence derives from studies linking occupational exposure to
      AChEis to chronic health symptoms that mirror those of ill GWV. Illness is again
      linked to lower activity of AChEi detoxifying enzymes and genotypes conferring
      less-avid AChEi detoxification. AChEi exposure satisfies Hill's presumptive
      criteria for causality, suggesting this exposure may be causally linked to excess
      health problems in GWV.

PMID- 18332429
TI  - IgG glycan hydrolysis by a bacterial enzyme as a therapy against autoimmune
      conditions.
AB  - EndoS from Streptococcus pyogenes efficiently hydrolyzes the functionally
      important and conserved N-linked glycan of IgG in human blood. Repeated i.v.
      administration of EndoS in rabbits completely hydrolyzes the glycans of the whole
      IgG pool, despite the generation of anti-EndoS antibodies. EndoS administration
      had no apparent effects on the health of the animals. EndoS hydrolysis of the IgG
      glycan has profound effects on IgG effector functions, such as complement
      activation and Fc receptor binding, suggesting that the enzyme could be used as
      an immunomodulatory therapeutic agent against IgG-mediated diseases. We
      demonstrate here that EndoS indeed has a protective effect in a mouse model of
      lethal IgG-driven immune (or idiopathic) thrombocytopenic purpura. EndoS
      pretreatment of pathogenic antibodies inhibits the development of disease, and
      the enzyme also rescues mice from already established disease when severe
      thrombocytopenia and s.c. bleeding have developed. These results identify EndoS
      as a potential therapeutic agent against diseases where pathogenic IgG antibodies
      are important and further emphasize antibody glycans as possible targets in
      future therapies against antibody-mediated autoimmune conditions.

PMID- 18332430
TI  - Variation in virulence among clades of Escherichia coli O157:H7 associated with
      disease outbreaks.
AB  - Escherichia coli O157:H7, a toxin-producing food and waterborne bacterial
      pathogen, has been linked to large outbreaks of gastrointestinal illness for more
      than two decades. E. coli O157 causes a wide range of clinical illness that
      varies by outbreak, although factors that contribute to variation in disease
      severity are poorly understood. Several recent outbreaks involving O157
      contamination of fresh produce (e.g., spinach) were associated with more severe
      disease, as defined by higher hemolytic uremic syndrome and hospitalization
      frequencies, suggesting that increased virulence has evolved. To test this
      hypothesis, we developed a system that detects SNPs in 96 loci and applied it to
      >500 E. coli O157 clinical strains. Phylogenetic analyses identified 39 SNP
      genotypes that differ at 20% of SNP loci and are separated into nine distinct
      clades. Differences were observed between clades in the frequency and
      distribution of Shiga toxin genes and in the type of clinical disease reported.
      Patients with hemolytic uremic syndrome were significantly more likely to be
      infected with clade 8 strains, which have increased in frequency over the past 5
      years. Genome sequencing of a spinach outbreak strain, a member of clade 8, also
      revealed substantial genomic differences. These findings suggest that an emergent
      subpopulation of the clade 8 lineage has acquired critical factors that
      contribute to more severe disease. The ability to detect and rapidly genotype
      O157 strains belonging to such lineages is important and will have a significant
      impact on both disease diagnosis and treatment guidelines.

PMID- 18332431
TI  - Specific requirement of the chromatin modifier mSin3B in cell cycle exit and
      cellular differentiation.
AB  - The Sin3-histone deacetylase (HDAC) corepressor complex is conserved from yeast
      to humans. Mammals possess two highly related Sin3 proteins, mSin3A and mSin3B,
      which serve as scaffolds tethering HDAC enzymatic activity, and numerous sequence
      specific transcription factors to enable local chromatin regulation at specific
      gene targets. Despite broad overlapping expression of mSin3A and mSin3B, mSin3A
      is cell-essential and vital for early embryonic development. Here, genetic
      disruption of mSin3B reveals a very different phenotype characterized by the
      survival of cultured cells and lethality at late stages of embryonic development
      with defective differentiation of multiple lineages-phenotypes that are
      strikingly reminiscent of those associated with loss of retinoblastoma family
      members or E2F transcriptional repressors. Additionally, we observe that, whereas
      mSin3B(-/-) cells cycle normally under standard growth conditions, they show an
      impaired ability to exit the cell cycle with limiting growth factors.
      Correspondingly, mSin3B interacts physically with the promoters of known E2F
      target genes, and its deficiency is associated with derepression of these gene
      targets in vivo. Together, these results reveal a critical role for mSin3B in the
      control of cell cycle exit and terminal differentiation in mammals and establish
      contrasting roles for the mSin3 proteins in the growth and development of
      specific lineages.

PMID- 18332432
TI  - A trispecies Aspergillus microarray: comparative transcriptomics of three
      Aspergillus species.
AB  - The full-genome sequencing of the filamentous fungi Aspergillus nidulans,
      Aspergillus niger, and Aspergillus oryzae has opened possibilities for studying
      the cellular physiology of these fungi on a systemic level. As a tool to explore
      this, we are making available an Affymetrix GeneChip developed for transcriptome
      analysis of any of the three above-mentioned aspergilli. Transcriptome analysis
      of triplicate batch cultivations of all three aspergilli on glucose and xylose
      media was used to validate the performance of the microarray. Gene comparisons of
      all three species and cross-analysis with the expression data identified 23 genes
      to be a conserved response across Aspergillus sp., including the xylose
      transcriptional activator XlnR. A promoter analysis of the up-regulated genes in
      all three species indicates the conserved XlnR-binding site to be 5'-GGNTAAA-3'.
      The composition of the conserved gene-set suggests that xylose acts as a
      molecule, indicating the presence of complex carbohydrates such as hemicellulose,
      and triggers an array of degrading enzymes. With this case example, we present a
      validated tool for transcriptome analysis of three Aspergillus species and a
      methodology for conducting cross-species evolutionary studies within a genus
      using comparative transcriptomics.

PMID- 18332433
TI  - Domestication of the donkey: timing, processes, and indicators.
AB  - Domestication of the donkey from the African wild ass transformed ancient
      transport systems in Africa and Asia and the organization of early cities and
      pastoral societies. Genetic research suggests an African origin for the donkey,
      but pinpointing the timing and location of domestication has been challenging
      because donkeys are uncommon in the archaeological record and markers for early
      phases of animal domestication are hard to determine. We present previously
      undescribed evidence for the earliest transport use of the donkey and new
      paleopathological indicators for early phases of donkey domestication. Findings
      are based on skeletal data from 10 approximately 5,000-year-old ass skeletons
      recently discovered entombed in an early pharaonic mortuary complex at Abydos,
      Middle Egypt, and a concurrent study of 53 modern donkey and African wild ass
      skeletons. Morphometric studies showed that Abydos metacarpals were similar in
      overall proportions to those of wild ass, but individual measurements varied.
      Midshaft breadths resembled wild ass, but midshaft depths and distal breadths
      were intermediate between wild ass and domestic donkey. Despite this, all of the
      Abydos skeletons exhibited a range of osteopathologies consistent with load
      carrying. Morphological similarities to wild ass show that, despite their use as
      beasts of burden, donkeys were still undergoing considerable phenotypic change
      during the early Dynastic period in Egypt. This pattern is consistent with recent
      studies of other domestic animals that suggest that the process of domestication
      is slower and less linear than previously thought.

PMID- 18332434
TI  - Alzheimer's disease is associated with reduced expression of energy metabolism
      genes in posterior cingulate neurons.
AB  - Alzheimer's disease (AD) is associated with regional reductions in
      fluorodeoxyglucose positron emission tomography (FDG PET) measurements of the
      cerebral metabolic rate for glucose, which may begin long before the onset of
      histopathological or clinical features, especially in carriers of a common AD
      susceptibility gene. Molecular evaluation of cells from metabolically affected
      brain regions could provide new information about the pathogenesis of AD and new
      targets at which to aim disease-slowing and prevention therapies. Data from a
      genome-wide transcriptomic study were used to compare the expression of 80
      metabolically relevant nuclear genes from laser-capture microdissected non-tangle
      bearing neurons from autopsy brains of AD cases and normal controls in posterior
      cingulate cortex, which is metabolically affected in the earliest stages; other
      brain regions metabolically affected in PET studies of AD or normal aging; and
      visual cortex, which is relatively spared. Compared with controls, AD cases had
      significantly lower expression of 70% of the nuclear genes encoding subunits of
      the mitochondrial electron transport chain in posterior cingulate cortex, 65% of
      those in the middle temporal gyrus, 61% of those in hippocampal CA1, 23% of those
      in entorhinal cortex, 16% of those in visual cortex, and 5% of those in the
      superior frontal gyrus. Western blots confirmed underexpression of those complex
      I-V subunits assessed at the protein level. Cerebral metabolic rate for glucose
      abnormalities in FDG PET studies of AD may be associated with reduced neuronal
      expression of nuclear genes encoding subunits of the mitochondrial electron
      transport chain.

PMID- 18332435
TI  - Corn-based ethanol production compromises goal of reducing nitrogen export by the
      Mississippi River.
AB  - Corn cultivation in the United States is expected to increase to meet demand for
      ethanol. Nitrogen leaching from fertilized corn fields to the Mississippi
      Atchafalaya River system is a primary cause of the bottom-water hypoxia that
      develops on the continental shelf of the northern Gulf of Mexico each summer. In
      this study, we combine agricultural land use scenarios with physically based
      models of terrestrial and aquatic nitrogen to examine the effect of present and
      future expansion of corn-based ethanol production on nitrogen export by the
      Mississippi and Atchafalaya Rivers to the Gulf of Mexico. The results show that
      the increase in corn cultivation required to meet the goal of 15-36 billion
      gallons of renewable fuels by the year 2022 suggested by a recent U.S. Senate
      energy policy would increase the annual average flux of dissolved inorganic
      nitrogen (DIN) export by the Mississippi and Atchafalaya Rivers by 10-34%.
      Generating 15 billion gallons of corn-based ethanol by the year 2022 will
      increase the odds that annual DIN export exceeds the target set for reducing
      hypoxia in the Gulf of Mexico to >95%. Examination of extreme mitigation options
      shows that expanding corn-based ethanol production would make the already
      difficult challenges of reducing nitrogen export to the Gulf of Mexico and the
      extent of hypoxia practically impossible without large shifts in food production
      and agricultural management.

PMID- 18332436
TI  - Modeling targeted layered containment of an influenza pandemic in the United
      States.
AB  - Planning a response to an outbreak of a pandemic strain of influenza is a high
      public health priority. Three research groups using different individual-based,
      stochastic simulation models have examined the consequences of intervention
      strategies chosen in consultation with U.S. public health workers. The first goal
      is to simulate the effectiveness of a set of potentially feasible intervention
      strategies. Combinations called targeted layered containment (TLC) of influenza
      antiviral treatment and prophylaxis and nonpharmaceutical interventions of
      quarantine, isolation, school closure, community social distancing, and workplace
      social distancing are considered. The second goal is to examine the robustness of
      the results to model assumptions. The comparisons focus on a pandemic outbreak in
      a population similar to that of Chicago, with approximately 8.6 million people.
      The simulations suggest that at the expected transmissibility of a pandemic
      strain, timely implementation of a combination of targeted household antiviral
      prophylaxis, and social distancing measures could substantially lower the illness
      attack rate before a highly efficacious vaccine could become available. Timely
      initiation of measures and school closure play important roles. Because of the
      current lack of data on which to base such models, further field research is
      recommended to learn more about the sources of transmission and the effectiveness
      of social distancing measures in reducing influenza transmission.

PMID- 18332437
TI  - A 16-bit parallel processing in a molecular assembly.
AB  - A machine assembly consisting of 17 identical molecules of 2,3,5,6-tetramethyl-1
      4-benzoquinone (DRQ) executes 16 instructions at a time. A single DRQ is
      positioned at the center of a circular ring formed by 16 other DRQs, controlling
      their operation in parallel through hydrogen-bond channels. Each molecule is a
      logic machine and generates four instructions by rotating its alkyl groups. A
      single instruction executed by a scanning tunneling microscope tip on the central
      molecule can change decisions of 16 machines simultaneously, in four billion
      (4(16)) ways. This parallel communication represents a significant conceptual
      advance relative to today's fastest processors, which execute only one
      instruction at a time.

PMID- 18332438
TI  - Bidirectional membrane tube dynamics driven by nonprocessive motors.
AB  - In cells, membrane tubes are extracted by molecular motors. Although individual
      motors cannot provide enough force to pull a tube, clusters of such motors can.
      Here, we investigate, using a minimal in vitro model system, how the tube pulling
      process depends on fundamental properties of the motor species involved.
      Previously, it has been shown that processive motors can pull tubes by dynamic
      association at the tube tip. We demonstrate that, remarkably, nonprocessive
      motors can also cooperatively extract tubes. Moreover, the tubes pulled by
      nonprocessive motors exhibit rich dynamics as compared to those pulled by their
      processive counterparts. We report distinct phases of persistent growth,
      retraction, and an intermediate regime characterized by highly dynamic switching
      between the two. We interpret the different phases in the context of a single
      species model. The model assumes only a simple motor clustering mechanism along
      the length of the entire tube and the presence of a length-dependent tube
      tension. The resulting dynamic distribution of motor clusters acts as both a
      velocity and distance regulator for the tube. We show the switching phase to be
      an attractor of the dynamics of this model, suggesting that the switching
      observed experimentally is a robust characteristic of nonprocessive motors. A
      similar system could regulate in vivo biological membrane networks.

PMID- 18332439
TI  - Enduring effects of early structured noise exposure on temporal modulation in the
      primary auditory cortex.
AB  - Studies have shown that acoustic experiences significantly contribute to the
      functional shaping of the structural organization and signal processing
      capacities of the mammalian auditory system during postnatal development. Here,
      we show how an early epoch of exposure to structured noise influences temporal
      processing in the rat primary auditory cortex documented immediately after
      exposure and again in adulthood. Pups were continuously exposed to broadband
      pulsed noise across the critical period for auditory system development.
      Immediately after cessation of exposure at postnatal day approximately 35 (P35)
      or approximately 55 days later (i.e., P90) in other rats, the temporal modulation
      transfer functions of cortical neurons were documented. We found that pulsed
      noise exposure at a low modulation rate significantly decreased cortical
      responses to repetitive stimuli presented across a range of higher modulation
      rates. The highest temporal rate at which temporal modulation-transfer function
      was at half of its maximum was reduced when compared with naive rats. Low-rate
      pulsed noise exposure also decreased cortical response synchronization at higher
      stimulus rates, as shown by vector strength and Rayleigh statistic measures.
      These postexposure changes endured into adulthood. These findings bear
      significant implications for the role of early sound experiences as contributors
      to the ontogeny of human auditory and language-related abilities and impairments.

PMID- 18332440
TI  - Integration of light and abscisic acid signaling during seed germination and
      early seedling development.
AB  - Seed germination is regulated by endogenous hormonal cues and external
      environmental stimuli such as water, low temperature, and light. After
      germination, the young seedling must rapidly establish its root system and the
      photoautotrophic capability appropriate to its surrounding environment. Light and
      the phytohormone abscisic acid (ABA) both regulate seed germination and seedling
      development, although how light and ABA signals are integrated at the molecular
      level is not understood. Here, we found that the previously described light
      signaling component HY5 also mediates ABA response in seed germination, early
      seedling growth, and root development in Arabidopsis. HY5 binds to the promoter
      of the transcription factor ABI5 gene with high affinity and is required for the
      expression of ABI5 and ABI5-targeted late embryogenesis-abundant genes in seeds.
      Chromatin immunoprecipitation also indicated that the binding of HY5 to the ABI5
      promoter is significantly enhanced by ABA. Overexpression of ABI5 restores ABA
      sensitivity in hy5 and results in enhanced light responses and shorter hypocotyls
      in the wild type. Our studies identified an unexpected mode of light and ABA
      signal integration that may help young seedlings better adapt to environmental
      stresses.

PMID- 18332441
TI  - Confinement of caspase-12 proteolytic activity to autoprocessing.
AB  - Caspase-12 is a dominant-negative regulator of caspase-1 (IL-1beta-converting
      enzyme) and an attenuator of cytokine responsiveness to septic infections. This
      molecular role for caspase-12 appears to be akin to the role of cFLIP in
      regulating caspase-8 in the extrinsic cell death pathway; however, unlike
      cFLIP/Usurpin, we demonstrate here that caspase-12 is catalytically competent. To
      examine these catalytic properties, rat caspase-12 was cloned, and the
      recombinant enzyme was used to examine the cleavage of macromolecular and
      synthetic fluorogenic substrates. Although caspase-12 could mediate
      autoproteolytic maturation of its own proenzyme, in both cis and trans, it was
      not able to cleave any other polypeptide substrate, including other caspase
      proenzymes, apoptotic substrates, cytokine precursors, or proteins in the
      endoplasmic reticulum that normally undergo caspase-mediated proteolysis. The
      dearth of potential substrates for caspase-12 also was confirmed by whole-cell
      diagonal-gel analysis. Autolytic cleavage within the caspase-12 proenzyme was
      mapped to a single site at the large-small subunit junction, ATAD(319), and this
      motif was recognized by caspase-12 when incorporated into synthetic fluorogenic
      substrates. The specific activity of caspase-12 with these substates was several
      orders of magnitude lower than caspases-1 and -3, highlighting its relative
      catalytic paucity. In intact cells, caspase-12 autoproteolysis occurred in the
      inhibitory complex containing caspase-1. We propose that the proteolytic activity
      of caspase-12 is confined to its own proenzyme and that autocleavage within the
      caspase-1 complex may be a means for temporal limitation of the inhibitory
      effects of caspase-12 on proinflammatory cytokine maturation.

PMID- 18332442
TI  - Renal replacement therapy in end-stage renal disease patients with chronic liver
      disease and ascites: role of peritoneal dialysis.
AB  - Chronic liver disease and cirrhosis account for several thousand deaths in the
      United States and often these patients have renal disease that progresses to end
      stage renal disease (ESRD), necessitating renal replacement therapy. These
      patients provide significant challenges to their physicians, especially in the
      management of their ESRD with dialysis. ESRD patients with chronic liver disease
      and ascites are more difficult to manage on hemodialysis (HD) due to their
      hemodynamic status and risk of bleeding. Peritoneal dialysis (PD) offers them a
      viable alternative, along with a stable hemodynamic status and a lower risk of
      bleeding. The overall morbidity and mortality as well as the risk of peritonitis
      appear to be almost similar between cirrhotic and non-cirrhotic PD patients. In
      the absence of clinical trials comparing HD versus PD in such a population, and
      despite the limited clinical observations, the authors support PD as a viable and
      effective form of renal replacement therapy for patients with ESRD and associated
      chronic liver disease with cirrhosis and ascites.

PMID- 18332443
TI  - Peritoneal dialysis in the comprehensive management of end-stage renal disease
      patients with liver cirrhosis and ascites: practical aspects and review of the
      literature.
AB  - The treatment of cirrhotic patients with ascites and end-stage renal disease is
      complex, due mainly to decreased effective arterial volume and hemodynamic
      instability. Peritoneal dialysis as a continuous therapy represents an
      alternative to hemodialysis-related intolerance. We report on our experience and
      that of others with cirrhotic patients with ascites treated by peritoneal
      dialysis. Hemodynamic tolerance was excellent in all patients and solute and
      water peritoneal transport increased to above the normal range in almost all
      cases. Morbidity and mortality were related principally to liver disease and
      other comorbidities. Peritoneal protein losses, initially high, decreased over
      time, maintaining serum albumin within the low normal range. The incidence of
      peritonitis was similar or slightly higher than usual in these patients, with
      peculiar etiology. The experiences with peritoneal dialysis suggest consideration
      of this treatment as the first choice for cirrhotic patients with ascites and
      that need to start dialysis.

PMID- 18332444
TI  - Acute cardiovascular functional effects of peritoneal dialysis: what do we know
      and why might it matter?

PMID- 18332445
TI  - Intravenous iron: not just for hemodialysis patients anymore.

PMID- 18332446
TI  - Catheter removal for fungal peritonitis: sooner or later?

PMID- 18332447
TI  - Fluoroscopic placement of peritoneal dialysis catheters: a harvest of the low
      hanging fruits.

PMID- 18332448
TI  - Peritoneal dialysis catheter placement by nephrologist.

PMID- 18332449
TI  - Acute central hemodynamic effects of a volume exchange in peritoneal dialysis.
AB  - BACKGROUND: Although peritoneal dialysis is considered to offer more hemodynamic
      stability than hemodialysis, the acute hemodynamic effects of peritoneal dialysis
      have only been investigated scarcely. The present study assesses the central
      hemodynamic impact of volume infusion using pH-adjusted icodextrin, thus avoiding
      interference of glucose, pH, and osmolarity. METHODS: Patients were randomized to
      3 different starting volumes (A: 1000 mL, B: 1500 mL, and C: 2500 mL) of
      icodextrin, followed by addition (A and B) or drainage (C) of 200 mL every 10
      minutes for 50 minutes. Local carotid systolic blood pressure (BP; as a surrogate
      for central BP), augmentation index, and augmentation pressure were measured by
      applanation tonometry before and after infusion of the starting volumes and after
      each volume change. RESULTS: We included 13 patients (median age 57 years).
      Baseline brachial BP was 126/77 mmHg. After infusion of the starting volume,
      carotid systolic BP and augmentation pressure increased by 4.7 mmHg (p = 0.006)
      and 3.1 mmHg (p = 0.015). Augmentation index increased by 5.7% (p = 0.04) and
      heart rate decreased by 2.6/minute (p = 0.006). Intraperitoneal pressure
      increased by 2.3 cm H(2)O (p = 0.03). No additional hemodynamic changes except
      for a rise in diastolic BP with increasing volume (p = 0.004) were observed after
      subsequent addition or removal of volumes. CONCLUSIONS: Infusion of peritoneal
      dialysis fluids causes an acute increase in carotid systolic BP, followed by a
      progressive rise in diastolic BP. These effects persist until complete drainage
      of the abdomen and may be due to an enhanced preload, resulting from
      intraperitoneal venous compression, and/or increased wave reflection.

PMID- 18332450
TI  - Intravenous iron sucrose in peritoneal dialysis patients with renal anemia.
AB  - OBJECTIVE: To explore the safety and efficacy of intravenous (IV) iron sucrose in
      maintenance peritoneal dialysis (PD). DESIGN: Randomized, controlled, parallel
      group single-center trial. SETTING: Blood Purification Center of Chaoyang,
      Beijing Capital University of Medical Science, China. METHODS: 46 patients on PD
      were involved in this trial. 26 patients received IV iron sucrose (200 mg iron)
      once per week for 4 weeks then once every other week for a further 4 weeks. The
      other 20 patients received oral ferrous succinate, 200 mg three times per day,
      for 8 weeks. Hemoglobin, hematocrit, serum ferritin (SF) level, and transferrin
      saturation (TSAT) were assessed at baseline and then again after 2, 4, and 8
      weeks of treatment. RESULTS: There were no differences between the IV and oral
      groups in terms of sex, age, duration of PD, mean dialysate dosage per day,
      erythropoietin dosage per week, or hematological parameters at baseline. After 4
      and 8 weeks of treatment, mean Hb and Hct were significantly increased in the IV
      group and were also significantly higher than those in the oral group. Levels of
      SF and TSAT were also significantly increased in the IV group, and significantly
      higher than in the oral group. After 8 weeks, the response rate in the IV group
      was 94.8%, which was significantly higher than that in the oral group. The mean
      erythropoietin dose was significantly lower in the IV group than in the oral
      group. Hb, Hct, SF, and TSAT levels were maintained between 4 and 8 weeks in the
      IV group despite the decrease in dose frequency. There were no adverse events
      with IV iron. Eight patients in the oral group had adverse gastrointestinal
      effects. CONCLUSION: IV iron sucrose is safe in PD patients. It increases Hb
      levels and serum iron parameters more effectively than oral iron; it is well
      tolerated and can permit reductions in the required dose of erythropoietin.

PMID- 18332451
TI  - Treatment of fungal peritonitis with a combination of intravenous amphotericin B
      and oral flucytosine, and delayed catheter replacement in continuous ambulatory
      peritoneal dialysis.
AB  - BACKGROUND: Fungal peritonitis (FP) is associated with significant mortality and
      high risk of peritoneal failure. The optimum treatment for peritoneal dialysis
      (PD)-associated FP remains unclear. Since January 2000 we have been treating FP
      with a combination of intravenous amphotericin B and oral flucytosine, together
      with deferred catheter replacement. We examined the clinical course and outcome
      of the FP patients treated with this approach (study group). An outcome
      comparison was also made to an alternatively treated historic cohort (control
      group). METHODS: This was a single-center retrospective study. The clinical
      course and outcome of 13 consecutive episodes of FP occurring in 13 patients
      treated between January 2000 and April 2005 with the study approach were
      examined. The patients were treated with an incremental dose of intravenous
      amphotericin B to a target dose of 0.75 - 1 mg/kg body weight/day, and oral
      flucytosine 1 g/day upon a diagnosis of FP at 3.77 +/- 0.93 days from
      presentation. Replacement of the peritoneal catheter was intended after complete
      clearing of effluent, after which, antifungal chemotherapy was continued for
      another 1 - 2 weeks. Their outcome was compared with 14 historic controls that
      were treated between April 1995 and December 1999. RESULTS: Mean age of the study
      group was 58.7 +/- 13.2 years; male-to-female ratio was 2:11; 6 (46.1%) were
      diabetic. All FP were caused by Candida species (C. albicans, 2; C. parapsilosis,
      8; C. glabrata, 3). Two (15.4%) patients died before resolution of the
      peritonitis. The dialysate effluent cleared in 11 patients (84.6%) after 13.2 +/-
      3.3 days of treatment, but 2 patients died of acute myocardial infarction before
      catheter replacement. Nine patients had their catheters replaced at day 26.7 +/-
      7.7 of treatment; all 9 returned to PD after a total of 31 +/- 12.2 days of
      antifungal chemotherapy. Reversible liver dysfunction was common with this
      regimen. When compared with the 14 cases in the historic control group (Candida
      species, 13; Trichosporon, 1), who were treated with amphotericin B, fluconazole,
      or a combination of the two, and the majority (78.6%) of whose catheters were
      removed before day 10 of presentation, the study group appeared to have a lower
      technique failure rate (30.8% vs 78.6%, p = 0.013) and similar all-cause
      mortality (30.7% vs 28.5%, p = NS), FP-related mortality (15.4% vs 28.5%, p =
      NS), and length of hospitalization (48.5 +/- 30.2 vs 57.0 +/- 37.7 days, p = NS).
      However, a significantly earlier commencement of antifungal treatment in the
      study group (3.8 +/- 0.9 vs 5.8 +/- 2.4 days, p = 0.012) could be an important
      confounder of outcome. CONCLUSIONS: Combination of intravenous amphotericin B and
      oral flucytosine with deferred catheter replacement appears to be associated with
      a relatively low incidence of PD technique failure, without affecting mortality
      in patients suffering from FP due to yeasts in this preliminary study.
      Nonetheless, drug-induced hepatic dysfunction was common; close monitoring during
      treatment is of paramount importance. The reasons accounting for the observed
      distinctive outcome remain unclear and further study is required to confirm the
      results and to investigate for the underlying mechanism.

PMID- 18332452
TI  - Fluoroscopically guided peritoneal dialysis catheter placement: long-term results
      from a single center.
AB  - OBJECTIVE: Despite percutaneous fluoroscopy ensuring appropriate placement of
      peritoneal dialysis (PD) catheters, the efficacy of this method is not well
      known. Therefore, we evaluated our long-term experience with fluoroscopy-assisted
      placement of PD catheters. PATIENTS AND METHODS: We retrospectively reviewed 134
      PD catheters in 114 PD patients that were treated in the PD center of a
      university-based hospital. We evaluated complications related to PD catheters,
      causes for catheter removal, and catheter survival. We used the multivariate Cox
      proportional hazard model to identify independent factors related to PD catheter
      survival. RESULTS: Early complications related to insertion included 1 case of
      pericatheter bleeding; there were no placement failures. Early complications
      occurred in 8.5% of patients. Most late complications were migration and leakage,
      which occurred in 10.4% and 9.7% of patients respectively. The most common cause
      for catheter removal was intractable and recurrent peritonitis. The 12- and 24
      month survival rates of the catheters were 80.0% and 74.9%. The most significant
      prognostic factor of percutaneous fluoroscopy-assisted PD catheter survival was
      late leakage (p < 0.01). CONCLUSIONS: In addition to the advantages of
      simplicity, minimal invasiveness, and relative safety, the survival rate of PD
      catheters placed using the percutaneous fluoroscopy-assisted method was
      comparable to that of more invasive methods. Percutaneous fluoroscopy-assisted
      placement of PD catheters should be considered when available, and may be
      preferred to other placement methods.

PMID- 18332453
TI  - Laparoscopic placement of Tenckhoff catheters for peritoneal dialysis: a safe,
      effective, and reproducible procedure.
AB  - BACKGROUND/AIMS: Currently there are several techniques for laparoscopic
      placement of peritoneal dialysis catheters. The aim of this paper is to describe
      our technique and outcomes. PATIENTS AND METHODS: Laparoscopic implantation of
      peritoneal catheters was performed in 100 consecutive patients. The technique
      employed laparoscopically guided musculofascial tunneling to maintain catheter
      orientation toward the deep pelvis, and adhesiolysis to eliminate
      compartmentalization that could affect completeness of dialysate drainage. Mean
      duration of surgery, hospital stay, morbidity, mortality, and catheter survival
      were assessed. Analysis of catheter survival was performed using the Kaplan-Meier
      method, with censoring of catheter loss due to death or successful
      transplantation. RESULTS: Mean operative time was 20 +/- 7 minutes and average
      duration of hospital stay was 3 +/- 1 days. There were no conversions from
      laparoscopy to conventional catheter insertion methods. No exit-site or tunnel
      infections, hemorrhagic complications, abdominal wall hernias, or catheter cuff
      extrusions were detected. No mortality occurred in this series of patients.
      Catheter survival was 97%, 95%, and 91% at 1, 2, and 3 years, respectively.
      CONCLUSIONS: The laparoscopic method described in this report is compliant with
      consensus guidelines for best-demonstrated practices in peritoneal access
      placement. Laparoscopy permits direct visualization of all procedure steps in a
      safe efficient reproducible manner. The laparoscopic approach afforded patients
      the advantage of short procedure times, a minimally invasive approach, and
      excellent outcomes. The results reported in this paper support our opinion that
      laparoscopic Tenckhoff catheter implantation should become the standard of care
      for clinical practice.

PMID- 18332454
TI  - The clinical usefulness of peritoneal dialysis fluids with neutral pH and low
      glucose degradation product concentration: an open randomized prospective trial.
AB  - BACKGROUND: Long-term peritoneal dialysis (PD) is associated with the development
      of various structural and functional changes to the peritoneal membrane when
      bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this
      study, we looked at patients that were treated with conventional PDFs and then
      changed to novel biocompatible PDFs with a neutral pH and a low concentration of
      glucose degradation products (GDPs) to investigate whether this change could
      result in the arrest or reversal of peritoneal membrane deterioration. METHODS:
      In an open label, randomized prospective trial, the clinical effects of
      conventional PDFs and biocompatible PDFs with neutral pH and very low
      concentration of GDPs were compared in 104 patients equally divided between both
      study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests,
      and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The
      target variables were the ratio of dialysate-to-plasma (D/P) creatinine,
      peritoneal ultrafiltration, residual renal function, dialysis adequacy indices,
      and effluent cancer antigen 125 (CA125). RESULTS: D/P creatinine values were not
      different in the two groups. Peritoneal ultrafiltration was significantly higher
      in the low-GDP PDF group than in the conventional PDF group at all follow-up
      times (4 months: 9.1 +/- 4.3 vs 6.0 +/- 3.0; 8 months: 8.3 +/- 3.4 vs 6.0 +/-
      3.0; 12 months: 8.9 +/- 3.3 vs 6.1 +/- 3.3 mL/g dextrose/day; p < 0.05).
      Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were
      significantly higher in the low-GDP PDF group than in the conventional PDF group.
      Residual renal function was not statistically significant. Effluent CA125 levels
      were significantly higher in the low-GDP PDF group at all follow-up visits (4
      months: 37.8 +/- 20.8 vs 22.0 +/- 9.5; 8 months: 41.2 +/- 20.3 vs 25.9 +/- 11.3;
      12 months: 40.4 +/- 21.4 vs 28.6 +/- 13.0 U/mL; p < 0.05). Among anuric patients,
      peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8
      months, and CA125 levels at all follow-up visits were significantly higher in
      patients treated with low-GDP PDF than those treated with conventional PDF.
      However, among anuric patients, D/P creatinine showed no significant differences
      between the low-GDP PDF group and the conventional PDF group. CONCLUSION: The use
      of biocompatible PDFs with neutral pH and low GDP concentration can contribute to
      improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an
      indicator of peritoneal membrane integrity in PD patients.

PMID- 18332455
TI  - Mortality in hepatitis C-positive patients treated with peritoneal dialysis.
AB  - OBJECTIVE: The published mortality data for patients with hepatitis C virus (HCV)
      infection and being treated with peritoneal dialysis (PD) are not available. The
      aim of this study was to determine the mortality of HCV patients undergoing PD.
      METHODS: We retrospectively reviewed 538 PD patients in our hospital from 1996 to
      2005. Of these patients, 75 (13.9%) were anti-HCV positive at the beginning of
      PD. We used Kaplan-Meier analysis to compare mortality between patients with and
      patients without HCV infection. The association between HCV infection and
      mortality was analyzed using multivariate Cox regression with adjustment for age,
      gender, residual renal function, and cardiovascular disease. RESULTS: A total of
      157 patients (39 HCV positive, 118 HCV negative) died during the 10-year follow
      up period. The mortality rate (52%, 39/75) of HCV-positive patients was
      significantly higher than that of HCV-negative patients (25.5%, 118/463; p <
      0.001). Cardiovascular mortality was 57.6% (68/118) among HCV-negative patients
      and 56.4% (22/39) among HCV-positive patients. Kaplan-Meier estimate showed that
      patients with HCV infection had higher mortality than those without (p < 0.001,
      log-rank). The result of Cox regression suggested that chronic HCV infection,
      independent of diabetes, was associated with 10-year mortality. The adjusted
      hazard ratios (HRs) of HCV infection and diabetes for mortality were 2.195 (95%
      CI: 1.486 - 3.243, p < 0.001) and 2.242 (95% CI: 1.533 - 3.277, p < 0.001).
      CONCLUSION: Our results show that the HCV-positive PD patients had a higher 10
      year mortality rate than the HCV-negative PD patients. The association between
      HCV infection and mortality was independent of diabetes. Cardiovascular
      mortality, infection, and arrhythmia were the leading causes of death among the
      PD patients with HCV infection.

PMID- 18332456
TI  - In vivo peritoneal surface area measurement in rats by micro-computed tomography
      (microCT).
AB  - Peritoneal dialysis (PD) uses the dynamic dialysis properties of the peritoneal
      membrane. The fraction of the anatomic peritoneal surface area (PSA) recruited is
      of importance for maximizing exchanges and is potentially impacted by parameters
      such as fill volume. We describe an in vivo assessment of the contact surface
      area by micro-computed tomography (microCT) using an iodinated contrast medium
      added to the PD fluid, a contrast agent presumed without surfactant property. In
      the isotropic volume (reconstructed voxel size 186 microm x 186 microm x 186
      microm), the iodinated PD fluid is automatically selected, thanks to its contrast
      difference with soft tissues, and its surface area is computed. The method was
      first tested on phantoms showing the ability to select the PD fluid volume and to
      measure its surface area. In vivo experiments in rat consisted of microCT
      acquisition of rat abdomen directly after intraperitoneal administration (10
      mL/100 g rat body weight) of a dialysis fluid containing 10% by volume iodinated
      contrast agent. Fluorescein isothiocyanate albumin was used as dilution marker.
      We found a strong linear relationship (R(2) = 0.98) between recruited PSA (cm(2))
      and rat weight (g) in the range of 235 to 435 g: recruited PSA = (1.61 weight +
      40.5) cm(2). Applying microCT with a fill volume of 10 mL/100 g rat body weight,
      the in vivo measured PSA was in the order of magnitude of the ex vivo anatomic
      PSA as determined by Kuzlan's formula, considered in most instances as the
      maximal surface area that can be recruited by PD fluid. This new methodology was
      the first to give an in vivo high-resolution isotropic three-dimensional (3-D)
      determination of the PSA in contact with dialysate. Its sensitivity allows us to
      take into account the recruitment of fine 3-D structures of the PSA membrane that
      were not accessible to previous 2-D-based imaging methodologies. Its in vivo
      application also integrates the physiological natural tensile stress of tissues.

PMID- 18332457
TI  - Acinetobacter peritoneal dialysis peritonitis: description and relation to the
      SPICE family of organisms.

PMID- 18332458
TI  - Eosinophilic peritonitis and ultrafiltration failure on initiation of CAPD.

PMID- 18332459
TI  - Peritoneal dialysis in Ontario.

PMID- 18332460
TI  - Reversing the decreasing peritoneal dialysis trend in Ontario.

PMID- 18332461
TI  - Secondary embedding of peritoneal dialysis catheters.

PMID- 18332462
TI  - Severe hypermagnesemia causing quadriparesis in a CAPD patient.

PMID- 18332463
TI  - Severe peritonitis due to Pantoea agglomerans in a CCPD patient.

PMID- 18332464
TI  - Malnutrition-inflammation score in peritoneal dialysis: growing reliability.

PMID- 18332465
TI  - Dose selection in phase I studies: why we should always go for the top.

PMID- 18332466
TI  - Involved-field radiotherapy before high-dose therapy and autologous stem-cell
      rescue in diffuse large-cell lymphoma: long-term disease control and toxicity.
AB  - PURPOSE: To analyze outcome, prognostic factors, and toxicities in patients with
      diffuse large-cell lymphoma (DLCL) who received involved-field radiotherapy
      (IFRT) before high-dose chemotherapy with autologous stem-cell rescue (ASCR).
      PATIENTS AND METHODS: Between January 1990 and August 2006, 164 patients with
      relapsed or refractory DLCL received IFRT at Memorial Sloan-Kettering Cancer
      Center (New York, NY) before high-dose chemotherapy and ASCR. IFRT was delivered
      to involved sites measuring more than 5 cm or to sites with residual disease more
      than 2 cm. Radiotherapy was administered in 1.5-Gy fractions twice daily to a
      total dose of 30 Gy. Progression-free survival and overall survival were
      calculated, and short- and long-term toxicity was assessed according to National
      Cancer Institute Common Toxicity Criteria (version 2.0). Median follow-up was 60
      months (range, 2 to 187 months). RESULTS: Two- and 5-year progression-free
      survival was 62% and 53%; 2- and 5-year overall survival was 67% and 58%,
      respectively. Sixty-seven patients relapsed; only 10 patients relapsed completely
      within the radiotherapy field. There were seven early treatment-related
      mortalities and 11 secondary cancers (including four myelodysplastic syndromes),
      one of which occurred within the IFRT site and five after total-body irradiation.
      CONCLUSION: Minimal treatment-related mortality and morbidity resulted from
      short, intensive, involved-field radiotherapy before high-dose chemotherapy and
      ASCR, which was incorporated into a salvage regimen for patients with
      relapsed/refractory DLCL. This chemoradiotherapy salvage regimen resulted in a
      low local relapse rate that could potentially translate into an improved total
      outcome.

PMID- 18332467
TI  - Identifying optimal biologic doses of everolimus (RAD001) in patients with cancer
      based on the modeling of preclinical and clinical pharmacokinetic and
      pharmacodynamic data.
AB  - PURPOSE: To use preclinical and clinical pharmacokinetic (PK)/pharmacodynamic
      (PD) modeling to predict optimal clinical regimens of everolimus, a novel oral
      mammalian target of rapamycin (mTOR) inhibitor, to carry forward to expanded
      phase I with tumor biopsy studies in cancer patients. PATIENTS AND METHODS:
      Inhibition of S6 kinase 1 (S6K1), a molecular marker of mTOR signaling, was
      selected for PD analysis in peripheral blood mononuclear cells (PBMCs) in a phase
      I clinical trial. PK and PD were measured up to 11 days after the fourth weekly
      dose. A PK/PD model was used to describe the relationship between everolimus
      concentrations and S6K1 inhibition in PBMCs of cancer patients and in PBMCs and
      tumors of everolimus-treated CA20948 pancreatic tumor-bearing rats. RESULTS: Time
      and dose-dependent S6K1 inhibition was demonstrated in human PBMCs. In the rat
      model, a relationship was shown between S6K1 inhibition in tumors or PBMCs and
      antitumor effect. This allowed development of a direct-link PK/PD model that
      predicted PBMC S6K1 inhibition-time profiles in patients. Comparison of rat and
      human profiles simulated by the model suggested that a weekly 20- to 30-mg dose
      of everolimus would be associated with an antitumor effect in an everolimus
      sensitive tumor and that daily administration would exert a greater effect than
      weekly administration at higher doses. CONCLUSION: A direct-link PK/PD model
      predicting the time course of S6K1 inhibition during weekly and daily everolimus
      administration allowed extrapolation from preclinical studies and first clinical
      results to select optimal doses and regimens of everolimus to explore in future
      clinical trials.

PMID- 18332468
TI  - Optimizing endocrine therapy for estrogen receptor-positive breast cancer:
      treating the right patients for the right length of time.

PMID- 18332469
TI  - Dose- and schedule-dependent inhibition of the mammalian target of rapamycin
      pathway with everolimus: a phase I tumor pharmacodynamic study in patients with
      advanced solid tumors.
AB  - PURPOSE: Everolimus is a selective mammalian target of rapamycin (mTOR) inhibitor
      with promising anticancer activity. In order to identify a rationally based dose
      and schedule for cancer treatment, we have conducted a tumor pharmacodynamic
      phase I study in patients with advanced solid tumors. PATIENTS AND METHODS: Fifty
      five patients were treated with everolimus in cohorts of 20, 50, and 70 mg weekly
      or 5 and 10 mg daily. Dose escalation depended on dose limiting toxicity (DLT)
      rate during the first 4-week period. Pre- and on-treatment steady-state tumor and
      skin biopsies were evaluated for total and phosphorylated (p) protein S6 kinase
      1, eukaryotic initiation factor 4E (elF-4E) binding protein 1 (4E-BP1),
      eukaryotic initiation factor 4G (eIF-4G), AKT, and Ki-67 expression. Plasma
      trough levels of everolimus were determined on a weekly basis before dosing
      during the first 4 weeks. RESULTS: We observed a dose- and schedule-dependent
      inhibition of the mTOR pathway with a near complete inhibition of pS6 and peIF-4G
      at 10 mg/d and >or= 50 mg/wk. In addition, pAKT was upregulated in 50% of the
      treated tumors. In the daily schedule, there was a correlation between everolimus
      plasma trough concentrations and inhibition of peIF4G and p4E-BP1. There was good
      concordance of mTOR pathway inhibition between skin and tumor. Clinical benefit
      was observed in four patients including one patient with advanced colorectal
      cancer achieving a partial response. DLTs occurred in five patients: one patient
      at 10 mg/d (grade 3 stomatitis) and four patients at 70 mg/wk (two with grade 3
      stomatitis, one with grade 3 neutropenia, and one with grade 3 hyperglycemia).
      CONCLUSION: Everolimus achieved mTOR signaling inhibition at doses below the DLT.
      A dosage of 10 mg/d or 50 mg/wk is recommended for further development.

PMID- 18332470
TI  - Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of
      rapamycin inhibitor everolimus in patients with advanced solid tumors.
AB  - PURPOSE: To identify the optimal regimen and dosage of the oral mammalian target
      of rapamycin inhibitor everolimus (RAD001). METHODS: We performed a dose
      escalation study in advanced cancer patients administering oral everolimus 5 to
      30 mg/wk, with pharmacokinetic (PK) and pharmacodynamic (PD) studies. PD data
      prompted investigation of 50 and 70 mg weekly and daily dosing at 5 and 10 mg.
      RESULTS: Ninety-two patients were treated. Dose-limiting toxicity was seen in one
      patient each at 50 mg/wk (stomatitis and fatigue) and 10 mg/d (hyperglycemia);
      hence, the maximum-tolerated dose was not reached. S6 kinase 1 activity in
      peripheral-blood mononuclear cells was inhibited for at least 7 days at doses
      >or= 20 mg/wk. Area under the curve increased proportional to dose, but maximum
      serum concentration increased less than proportionally at doses >or= 20 mg/wk.
      Terminal half-life was 30 hours (range, 26 to 38 hours). Partial responses were
      observed in four patients, and 12 patients remained progression free for >or= 6
      months, including five of 10 patients with renal cell carcinoma. CONCLUSION:
      Everolimus was satisfactorily tolerated at dosages up to 70 mg/wk and 10 mg/d
      with predictable PK. Antitumor activity and PD in tumors require further clinical
      investigation. Doses of 20 mg/wk and 5 mg/d are recommended as appropriate
      starting doses for these studies.

PMID- 18332471
TI  - Letrozole compared with tamoxifen for elderly patients with endocrine-responsive
      early breast cancer: the BIG 1-98 trial.
AB  - PURPOSE: To explore potential differences in efficacy, treatment completion, and
      adverse events (AEs) in elderly women receiving adjuvant tamoxifen or letrozole
      for five years in the Breast International Group (BIG) 1-98 trial. METHODS: This
      report includes the 4,922 patients allocated to 5 years of letrozole or tamoxifen
      in the BIG 1-98 trial. The median follow-up was 40.4 months. Subpopulation
      Treatment Effect Pattern Plot (STEPP) analysis was used to examine the patterns
      of differences in disease-free survival and incidences of AEs according to age.
      In addition, three categoric age groups were defined: "younger postmenopausal"
      patients were younger than 65 years (n = 3,127), "older" patients were 65 to 74
      years old (n = 1,500), and "elderly" patients were 75 years of age or older (n =
      295). RESULTS: Efficacy results for subpopulations defined by age were similar to
      the overall trial results: Letrozole significantly improved disease-free survival
      (DFS), the primary end point, compared with tamoxifen. Elderly patients were less
      likely to complete trial treatment, but at rates that were similar in the two
      treatment groups. The incidence of bone fractures, observed more often in the
      letrozole group, did not differ by age. In elderly patients, letrozole had a
      significantly higher incidence of any grade 3 to 5 protocol-specified non
      fracture AE compared with tamoxifen (P = .002), but differences were not
      significant for thromboembolic or cardiac AEs. CONCLUSION: Adjuvant treatment
      with letrozole had superior efficacy (DFS) compared with tamoxifen in all age
      groups. On the basis of a small number of patients older than 75 years (6%), age
      per se should not unduly affect the choice of adjuvant endocrine therapy.

PMID- 18332472
TI  - Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant
      tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast
      And Bowel Project B-33 trial.
AB  - PURPOSE: Patients with early-stage, hormone receptor-positive breast cancer have
      considerable residual risk for recurrence after completing 5 years of adjuvant
      tamoxifen. In May 2001, the National Surgical Adjuvant Breast and Bowel Project
      (NSABP) initiated accrual to a randomized, placebo-controlled, double-blind
      clinical trial to evaluate the steroidal aromatase inhibitor exemestane as
      extended adjuvant therapy in this setting. PATIENTS AND METHODS: Postmenopausal
      patients with clinical T(1-3)N(1)M(0) breast cancer who were disease free after 5
      years of tamoxifen were randomly assigned to 5 years of exemestane (25 mg/d
      orally) or 5 years of placebo. Our primary aim was to test whether exemestane
      prolongs disease-free survival (DFS). In October 2003, results of National Cancer
      Institute of Canada (NCIC) MA.17 showing benefit from adjuvant letrozole in this
      setting necessitated termination of accrual to B-33, unblinding, and offering of
      exemestane to patients in the placebo group. RESULTS: At the time of unblinding,
      1,598 patients had been randomly assigned; 72% in the exemestane group continued
      on exemestane and 44% in the placebo group elected to receive exemestane. With 30
      months of median follow-up, original exemestane assignment resulted in a
      borderline statistically significant improvement in 4-year DFS (91% v 89%;
      relative risk [RR] = 0.68; P = .07) and in a statistically significant
      improvement in 4-year relapse-free survival (RFS; 96% v 94%; RR = 0.44; P =
      .004). Toxicity, assessed up to time of unblinding, was acceptable for the
      adjuvant setting. CONCLUSION: Despite premature closure and crossover to
      exemestane by a substantial proportion of patients, original exemestane
      assignment resulted in non-statistically significant improvement in DFS and in
      statistically significant improvement in RFS.

PMID- 18332473
TI  - Occult axillary node metastases in breast cancer are prognostically significant:
      results in 368 node-negative patients with 20-year follow-up.
AB  - PURPOSE: In breast cancer, sentinel lymph node (SLN) biopsy allows the routine
      performance of serial sections and/or immunohistochemical (IHC) staining to
      detect occult metastases missed by conventional techniques. However, there is no
      consensus regarding the optimal method for pathologic examination of SLN, or the
      prognostic significance of SLN micrometastases. PATIENTS AND METHODS: In 368
      patients with axillary node-negative invasive breast cancer, treated between 1976
      and 1978 by mastectomy, axillary dissection, and no systemic therapy, we
      reexamined the axillary tissue blocks following our current pathologic protocol
      for SLN. Occult lymph node metastases were categorized by pattern of staining
      (immunohistochemically positive or negative [IHC+/-], hematoxylin-eosin staining
      positive or negative [H & E +/-]), number of positive nodes (0, 1, > 1), number
      of metastatic cells (0, 1 to 20, 21 to 100, > 100), and largest cluster size
      (<or= 0.2 mm [pN0(i+)], 0.3 to 2.0 mm [pN1(mi)], > 2.0 mm [pN1a]). We report 20
      year results as overall survival (OS), disease-free survival (DFS), and disease
      specific death (DSD). RESULTS: A total of 23% of patients (83 of 368) were
      converted to node-positive. Of these, 73% were <or= 0.2 mm in size (pN0(i+)), 20%
      were 0.3 to 2.0 mm (pN1(mi)), and 6% were more than 2 mm (pN1a). On univariate
      and multivariate analysis, pattern of staining, number of positive nodes, number
      of metastatic cells, and cluster size were all significantly related to both DFS
      and DSD. On multivariate analysis, each of these measures had significance
      comparable to, or greater than, tumor size, grade or lymphovascular invasion.
      CONCLUSION: In breast cancer patients staged node-negative by conventional single
      section pathology, occult axillary node metastases detected by our current
      pathologic protocol for SLN are prognostically significant.

PMID- 18332474
TI  - Efficacy, toxicity, and quality of life in older women with early-stage breast
      cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG
      intergroup trial MA.17.
AB  - PURPOSE: National Cancer Institute of Canada Clinical Trials Group trial MA.17
      randomly assigned 5,187 postmenopausal, hormone-receptor-positive patients with
      early breast cancer who completed 5 years of tamoxifen to receive either
      letrozole or placebo. At 30 months median follow-up, letrozole significantly
      improved disease-free survival (DFS) in all patients and overall survival (OS) in
      node-positive patients. Breast cancer incidence increases with age and more than
      1,300 women age 70 years or older were enrolled onto MA.17, making it ideal to
      explore the benefits, toxicities, and quality of life (QOL) impact of letrozole
      on older women. PATIENTS AND METHODS: In this study, 5,169 randomly assigned
      patients were divided into three age groups: younger than 60 years (n = 2,152),
      60 to 69 years (n = 1,694), and >or= 70 years (n = 1,323). Log-rank test was used
      to compare differences in DFS, distant-disease-free survival, and OS between age
      and treatment groups, and Cox models were used to estimate hazard ratios and
      associated 95% CIs. QOL was measured using the Medical Outcomes Short Form-36 and
      the Menopause-Specific Quality-of-Life questionnaire. RESULTS: At 4 years, DFS
      demonstrated statistically significant differences favoring letrozole only in
      patients age younger than 60 years (hazard ratio = 0.46; P = .0004); there was no
      interaction between age and treatment, indicating a similar effect of letrozole
      among all age groups. There was no difference in toxicity or QOL at 24 months
      among letrozole- and placebo-treated patients age >or= 70 years. CONCLUSION:
      Healthy patients age 70 years and older completing 5 years of tamoxifen should be
      considered for extended adjuvant therapy with letrozole.

PMID- 18332475
TI  - Late extended adjuvant treatment with letrozole improves outcome in women with
      early-stage breast cancer who complete 5 years of tamoxifen.
AB  - PURPOSE: The National Cancer Institute of Canada Clinical Trials Group MA.17
      trial examined the efficacy of letrozole (LET) started within 3 months of 5 years
      of adjuvant tamoxifen in postmenopausal hormone receptor-positive early-stage
      breast cancer. When the trial was unblinded, patients who received placebo (PLAC)
      were offered LET. PATIENTS AND METHODS: This cohort analysis describes the
      outcomes of women assigned PLAC at the initial random assignment after
      unblinding. Efficacy outcomes of women who chose LET (PLAC-LET group) were
      compared with those who did not (PLAC-PLAC group) by the hazard ratios and by P
      values calculated from Cox models that adjusted for imbalances between the
      groups. Toxicity analyses included only events that occurred after unblinding.
      RESULTS: There were 1,579 women in the PLAC-LET group (median time from
      tamoxifen, 2.8 years) and 804 in the PLAC-PLAC group. Patients in the PLAC-LET
      group were younger; had a better performance status; and were more likely to have
      had node-positive disease, axillary dissection, and adjuvant chemotherapy than
      those in the PLAC-PLAC group. At a median follow-up of 5.3 years, disease-free
      survival (DFS; adjusted hazard ratio [HR], 0.37; 95% CI, 0.23 to 0.61; P < .0001)
      and distant DFS (HR, 0.39; 95% CI, 0.20 to 0.74; P = .004) were superior in the
      PLAC-LET group. More self-reported new diagnoses of osteoporosis and
      significantly more clinical fractures occurred in the women who took LET (5.2% v
      3.1%, P = .02). CONCLUSION: Interpretation of this cohort analysis suggests that
      LET improves DFS and distant DFS even when there has been a substantial period of
      time since the discontinuation of prior adjuvant tamoxifen.

PMID- 18332476
TI  - Alzheimer's and non-alzheimer's dementia: a critical review of pharmacological
      and nonpharmacological strategies.
AB  - OBJECTIVE: Dementia is an age-related progressive neurodegenerative disorder
      afflicting about 5% of the world's population, and it is expected to grow
      dramatically in the future keeping in view our ageing society. Currently
      available medications appear to be able to produce moderate symptomatic benefits
      but do not to stop disease progression. In this article, the management of the
      disorder, including the currently available drugs as well as psychosocial
      strategies, is discussed. METHODS: A computerized search on Pubmed from 1980 to
      2006 was carried out and all articles evaluated and graded on NICE guidelines.
      RESULTS AND CONCLUSIONS: Currently evaluated and accepted medications only bring
      about a reduction in the deteriorating course. A combination of pharmacotherapy
      and psychosocial management is the need of the hour.

PMID- 18332477
TI  - The food and drug legislation of 1906.
AB  - Pray for the welfare of government; since were it not for the fear of government;
      men would swallow each other alive.

PMID- 18332479
TI  - The see-saw of differentiation: tipping the chromatin balance.
AB  - Histone modifications, specifically, methylation of lysine residues in histone 3
      (H3), determine chromatin structure and accessibility for transcription. A recent
      study by Bernstein and Lander identified a unique pattern of H3 methylation at
      the promoter region of developmental genes in pluripotent stem cells. The pattern
      consists of the simultaneous presence of a silencing mark [methylation of Lys(27)
      on H3 (H3K27me)] and an activation mark (H3K4me). This bivalent mark seems
      associated with a poised state of transcription and resolves upon differentiation
      largely into either H3K27me or H3K4me. Skin fibroblasts that can be reverted in
      culture to the pluripotent stage show re-establishment of the bivalent chromatin
      pattern. This switch in chromatin states may be key to our understanding of
      developmental and tissue specific regulation of gene expression and may be
      therapeutically useful in regenerative medicine.

PMID- 18332480
TI  - SOCS3 in liver regeneration and hepatocarcinoma.
AB  - Cytokine responses are stringently controlled by a family of proteinsSTAT3 termed
      the suppressors of cytokine signaling (SOCS), and deregulation of SOCS function
      is associated with many diseases, including several cancers, disorders in
      hematopoiesis, and autoimmune diseases. Our current understanding of the
      divergent roles of SOCS3 has recently improved and indicates that SOCS3 is
      critical in modulating cytokine-mediated and neoplastic-proliferative responses
      in the liver. The generation of hepatocyte-specific Socs3 knockout mice suggests
      that loss of SOCS3 expression encourages hepatocyte proliferation, survival, and
      hepatocellular carcinoma formation. By elucidating the regulation of pathways
      leading to liver regeneration we may gain useful insights to control liver
      disease and tumor growth.

PMID- 18332481
TI  - Oncogenic ras-induced expression of cytokines: a new target of anti-cancer
      therapeutics.
AB  - The Ras family of small guanosine triphosphatases normally transmit signals from
      cell surface receptors to the interior of the cell. Stimulation of cell surface
      receptors leads to the activation of guanine exchange factors, which, in turn,
      convert Ras from an inactive GDP-bound state to an active GTP-bound state.
      However, in one third of human cancers, RAS is mutated and remains in the
      constitutively active GTP-bound state. In this oncogenic state, RAS activates a
      constellation of signaling that is known to promote tumorigenesis. One
      consequence of this oncogenic RAS signal in cancer cells is the upregulation of
      the cytokines interleukin (IL)-6, IL-8, and chemokine growth-regulated oncogene 1
      (GRO-1). We review the evidence supporting a role for these cytokines in
      oncogenic RAS-driven solid tumors.

PMID- 18332482
TI  - Lipid autacoids in inflammation and injury responses: a matter of privilege.
AB  - Host defense is essential to all vertebrates, and programs of inflammation and
      wound healing must be highly integrated in tissue and organ structures, such as
      the skin, cornea, and mucosa, that provide crucial barriers and interfaces with
      the external environment. Certain aspects of inflammation and wound healing have
      posed a conundrum for biologists, especially to the extent that the two programs
      may appear to operate in opposition to each other. The recruitment of neutrophils
      to injured tissue, for example, is essential to inflammation and defense against
      infection, but can at the same time impair wound healing. One mechanism for
      regulating this duality is provided by lipid autacoids, which act to restrain
      leukocyte activation and to promote the resolution of inflammation. Emerging
      evidence indicates that lipid autacoids also have a central role in wound healing
      and in fact mediate a privileged injury response, as is observed in the cornea,
      characterized by rapid healing as well as effective host defense.

PMID- 18332483
TI  - Cardiac glycosides as novel cancer therapeutic agents.
AB  - The class of steroid-like compounds designated cardiac glycosides includes well
      known drugs such as digoxin, digitoxin, and ouabain. Their continued efficacy in
      treatment of congestive heart failure and as anti-arrhythmic agents is well
      appreciated. Less well known, however, is the emerging role of this category of
      compounds in the prevention and/or treatment of proliferative diseases such as
      cancer. New findings within the past five years have revealed these compounds to
      be involved in complex cell-signal transduction mechanisms, resulting in
      selective control of human tumor but not normal cellular proliferation. As such,
      they represent a promising form of targeted cancer chemotherapy. New clinical
      studies of their anticancer potential as single or adjuvant treatments may
      provide insight into these potentially valuable therapeutic options. This review
      focuses on recent findings on cellular pharmacology of cardiac glycosides as they
      relate to treatment of human cancer and attempts to explain why these agents have
      been overlooked in the past.

PMID- 18332486
TI  - Toward a policy-relevant analysis of geographic and racial/ethnic disparities in
      child health.
AB  - Extreme racial/ethnic disparities exist in children's access to "opportunity
      neighborhoods." These disparities arise from high levels of residential
      segregation and have implications for health and well-being in childhood and
      throughout the life course. The fact that health disparities are rooted in social
      factors, such as residential segregation and an unequal geography of opportunity,
      should not have a paralyzing effect on the public health community. However, we
      need to move beyond conventional public health and health care approaches to
      consider policies to improve access to opportunity-rich neighborhoods through
      enhanced housing mobility, and to increase the opportunities for healthy living
      in disadvantaged neighborhoods.

PMID- 18332487
TI  - Challenges to using a business case for addressing health disparities.
AB  - The authors consider the challenges to quantifying both the business case and the
      social case for addressing disparities, which is central to achieving equity in
      the U.S. health care system. They describe the practical and methodological
      challenges faced by health plans exploring the business and social cases for
      undertaking disparity-reducing interventions. Despite these challenges, sound
      business and quality improvement principles can guide health care organizations
      seeking to reduce disparities. Place-based interventions may help focus resources
      and engage health care and community partners who can share in the costs of-and
      gains from-such efforts.

PMID- 18332488
TI  - Targeting health disparities: a model linking upstream determinants to downstream
      interventions.
AB  - Certain social/environmental factors put some groups at extraordinary risk for
      adverse health outcomes, creating health disparities. We present a downward
      causal model, originating at the population level and ending at disease, with
      psychological and behavioral responses linking the two. This approach identifies
      how specific social environments "get under the skin" to cause disease,
      illustrated with the disparity in mortality from aggressive premenopausal breast
      cancer suffered by black women. Broadening our lens to consider the entire chain
      of causal factors, spanning multiple levels and interacting across the life span,
      heightens our ability to craft specific interventions to address group
      differences in health.

PMID- 18332489
TI  - The gap gets bigger: changes in mortality and life expectancy, by education, 1981
      2000.
AB  - In this paper we examine educational disparities in mortality and life expectancy
      among non-Hispanic blacks and whites in the 1980s and 1990s. Despite increased
      attention and substantial dollars directed to groups with low socioeconomic
      status, within race and gender groups, the educational gap in life expectancy is
      rising, mainly because of rising differentials among the elderly. With the
      exception of black males, all recent gains in life expectancy at age twenty-five
      have occurred among better-educated groups, raising educational differentials in
      life expectancy by 30 percent. Differential trends in smoking-related diseases
      explain at least 20 percent of this trend.

PMID- 18332490
TI  - Race, ethnicity, and the education gradient in health.
AB  - Using pooled data from the 2000-2006 National Health Interview Survey, we
      document how the relationship between education and a broad range of health
      measures varies by race/ethnicity and nativity. We found that education is a more
      powerful determinant of health behaviors and outcomes for some groups than it is
      for others. In addition, the education differentials for foreign-born groups are
      typically more modest than those for corresponding native-born populations. We
      also show how the education-health relationship varies across Hispanic and Asian
      subgroups. We argue that any intervention for eliminating health disparities must
      take these patterns into account.

PMID- 18332492
TI  - When does a difference become a disparity? Conceptualizing racial and ethnic
      disparities in health.
AB  - Definitions of racial and ethnic disparities fall along a continuum from
      differences with little connotation of being unjust to those that result from
      overt discrimination. Where along this continuum one decides that a racial
      difference becomes a disparity is subjective, but the magnitude of the injustice
      is generally proportional to how much control a person is perceived to have over
      the cause of the difference in health. The degree to which one sees environmental
      factors and social context as shaping choices has important implications for the
      measurement of disparities and ultimately for directing efforts to eliminate
      them.

PMID- 18332493
TI  - Collecting adequate data on racial and ethnic disparities in health: the
      challenges continue.
AB  - Data limitations continue to pose challenges for efforts to identify racial and
      ethnic disparities in health and health care and analyze the underlying causes.
      Given budget constraints, the most feasible federal strategies to improve
      national data are those requiring only modest expenditures. Collaborations among
      private and public stakeholders hold promise for improving estimation methods and
      assessing disparities among small populations.

PMID- 18332495
TI  - New evidence regarding racial and ethnic disparities in mental health: policy
      implications.
AB  - Minorities have, in general, equal or better mental health than white Americans,
      yet they suffer from disparities in mental health care. This paper reviews the
      evidence for mental health and mental health care disparities, comparing them to
      patterns in health. Strategies for addressing disparities in health care, such as
      improving access to and quality of care, should also work to eliminate mental
      health care disparities. In addition, a diverse mental health workforce, as well
      as provider and patient education, are important to eliminating mental health
      care disparities.

PMID- 18332496
TI  - Giving policy some teeth: routes to reducing disparities in oral health.
AB  - Despite improvements in oral health status and clear links between oral and
      systemic health, oral health is not accorded the same importance in health care
      policy as is general health. This review of oral health disparities over the life
      span documents the results of this inequity. Dental concerns and unmet dental
      treatment needs, especially among vulnerable populations, are not well addressed
      in oral health policies. We offer examples of discrepancies between policy and
      needs and examples of successful interventions that integrate oral health care
      with informed policy.

PMID- 18332497
TI  - Disparities in human resources: addressing the lack of diversity in the health
      professions.
AB  - African Americans, Latinos, and American Indians are severely underrepresented in
      the health professions. A strong case for diversity may be made on the grounds of
      civil rights, public health and educational benefit, and business gains.
      Improving the diversity of the health professions requires multiprong strategies
      addressing the educational pipeline, admissions policies and the institutional
      culture at health professions schools, and the broader policy environment.

PMID- 18332499
TI  - The medical tongue: U.S. laws and policies on language access.
AB  - For twenty-three million Americans who speak English less than "very well,"
      language barriers lead to lower quality of and worse access to health care.
      Although the breadth of existing federal and state language access laws might
      seem sufficient, the lack of comprehensive implementation and enforcement leaves
      millions of patients with limited English proficiency forced to accept a lower
      quality of care than English speakers receive. This paper reviews existing laws
      and offers solutions focusing on five themes: access, funding, education, quality
      improvement, and accountability. Improving language access is essential to ensure
      that the language one speaks does not affect one's health or mortality.

PMID- 18332500
TI  - State variation in health insurance coverage for U.S. citizen children of
      immigrants.
AB  - In this paper we compare health insurance coverage for U.S. citizen children in
      all-citizen and mixed families in the fifteen states with the largest share of
      children in mixed families. Insurance coverage is lower and state variation in
      coverage is higher for children in mixed families vis-a-vis children in all
      citizen families. The main challenges for states are tackling uninsurance among
      all low-income children and addressing the very low rates of employer-sponsored
      insurance for all low-income children and for children in all mixed families,
      regardless of income. We discuss state policy options to address the needs of
      children in mixed families.

PMID- 18332501
TI  - Moving beyond access: achieving equity in state health care reform.
AB  - The Institute of Medicine's 2003 Unequal Treatment report raised the public's and
      policymakers' awareness of racial and ethnic health care disparities, but federal
      policy-makers have implemented few of the report's more than two dozen
      recommendations. State health care reform efforts, however, are gaining support
      around the country and have great potential to reduce health care inequality.
      This paper offers a policy framework to explore how states can move toward
      eliminating disparities by addressing health care access and quality, state
      health care infrastructure, patient and community empowerment, state policy
      infrastructure, and social and community determinants of health.

PMID- 18332502
TI  - Reducing racial and social-class inequalities in health: the need for a new
      approach.
AB  - It is well known that people in racial and ethnic minority groups and in lower
      social-class positions have higher morbidity and mortality rates from virtually
      every disease. To effectively deal with the problem, we will need to adopt a more
      appropriate conceptual model that focuses on the fundamental determinants of
      health, we will need to understand how important this is for all Americans as a
      society, and we will need to better deal with the issues people care about: their
      children, homes, jobs, safety, education, families, retirement, and future
      prospects.

PMID- 18332503
TI  - The Chinese health system at a crossroads.
AB  - The Chinese government has committed to increasing government funding for health
      care by directing 1-1.5 percent of its gross domestic product to universal basic
      health care. However, China is at a loss as to how to transform its new money
      into efficient and effective health care. This paper critically examines the
      various options currently under heated debate in China. We argue that unless
      China tackles the root cause of unaffordable health care--rapid cost inflation
      caused by an irrational and wasteful health care delivery system--much of the new
      money is likely to be captured by providers as higher income and profits.

PMID- 18332504
TI  - Medigap coverage and Medicare spending: a second look.
AB  - Medicare supplemental insurance (Medigap) provides important financial
      protections for many low- and moderate-income beneficiaries in Medicare's
      traditional fee-for-service program. However, conventional wisdom among
      policymakers holds that Medigap coverage substantially raises Medicare claims
      costs. This report uses detailed diagnosis data provided by three large Medigap
      insurers, information from the Medicare Current Beneficiary Survey, and the
      Medicare 5 percent sample file to reexamine the impact of Medigap coverage on
      Medicare spending. We conclude that previous studies might have overestimated the
      impact of Medigap coverage on Medicare costs and that past projections of
      potential Medicare cost savings from restrictions on Medigap coverage probably
      are overstated.

PMID- 18332505
TI  - Health insurance coverage in Central and Eastern Europe: trends and challenges.
AB  - Health insurance systems in Central and Eastern Europe have evolved in different
      ways from the centralized health systems inherited from the Soviet era, but there
      remain common trends and challenges in the region. Health spending is low in
      comparison to the spending of pre-2004 European Union members, but population
      aging, medical technology, economic growth, and heightened expectations will
      generate major spending pressures. Social health insurance is the dominant model
      in the region, but coverage is uneven. Key3reform issues include identifying ways
      to encourage additional investment in the health sector; and defining formal
      benefit packages, copayments, and the role of private insurance.

PMID- 18332506
TI  - Immunization and the Millennium Development Goals: progress and challenges in
      Latin America and the Caribbean.
AB  - The child mortality rate has been greatly reduced in Latin America and the
      Caribbean (LAC). More than half of the gains in reducing child mortality are
      attributable to immunization. The Revolving Fund of the Pan American Health
      Organization contributed to this achievement by catalyzing policy innovations
      that sustained national immunization programs, such as vaccine legislation and
      budgetary decrees to ensure delivery of services. In addition to measuring the
      impact of immunization on the child mortality reduction target of the Millennium
      Development Goals in the LAC region, this paper provides a policy framework to
      ensure that the rest of the target is reached.

PMID- 18332509
TI  - Disparities in physician care: experiences and perceptions of a multi-ethnic
      America.
AB  - This 2007 Harvard School of Public Health/Robert Wood Johnson Foundation survey
      of 4,334 randomly selected U.S. adults compared perceptions of the quality of
      physician care among fourteen racial and ethnic groups with those of whites. On
      each measure examined, at least five and as many as eleven subgroups perceived
      their care to be significantly worse than care for whites. In many instances,
      subgroups were at least fifteen percentage points more negative than whites. This
      was true for Central/South Americans, Chinese Americans, and Korean Americans on
      five of seven measures. Many of the differences remained after socioeconomic
      characteristics and language skills were controlled for.

PMID- 18332510
TI  - Do hospitals provide lower-quality care to minorities than to whites?
AB  - Using three years of state inpatient discharge data from thirteen states, we
      computed, for each hospital, race/ethnicity-specific quality measures using the
      Agency for Healthcare Research and Quality inpatient quality indicators and
      patient safety indicators. We found that risk-adjusted quality indicators for
      blacks, Hispanics, and Asians were not statistically worse than corresponding
      quality indicators for whites in the same hospital. We conclude that when whites
      and minorities are admitted to the hospital for the same reason or receive the
      same hospital procedure, they receive the same quality of care. Only a few
      hospitals provide lower quality of care to minorities than to whites.

PMID- 18332511
TI  - The characteristics and performance of hospitals that care for elderly Hispanic
      Americans.
AB  - The site of care may play an important role in health care disparities. We
      examined the 5 percent of U.S. hospitals with the highest proportion of elderly
      Hispanic patients and found that these hospitals cared for more than half of
      elderly Hispanics. These hospitals were more often for-profit, with higher rates
      of Medicaid patients and low nurse-staffing levels. They also provided a modestly
      lower quality of care for common medical conditions. Our finding that care for
      Hispanics is concentrated among a small number of hospitals provides an
      opportunity for targeted efforts to improve care for this group of Americans.

PMID- 18332512
TI  - Community variation: disparities in health care quality between Asian and white
      medicare beneficiaries.
AB  - Few studies have focused on Asian-white disparities. This study examines the use
      of selected cancer screening and diabetes services under the traditional Medicare
      program of whites and Asians by socioeconomic status and among U.S. metropolitan
      statistical areas in which elderly Asians reside. It demonstrates that existing
      data, with enrichment, can be used to examine Asian-white disparities. It finds
      that Asians often receive poorer quality of care than whites, but disparities
      differ among metropolitan areas. This research enables policymakers to better
      understand and target resources to address Asian-white disparities at the
      national and local community levels.

PMID- 18332513
TI  - Improving coverage and access for immigrant Latino children: the Los Angeles
      healthy kids program.
AB  - A large number of California counties have recently taken bold steps to extend
      health insurance to all poor and near-poor children through county-based
      Children's Health Initiatives. One initiative, the Los Angeles Healthy Kids
      program, extends coverage to uninsured children in families with incomes below
      300 percent of the federal poverty level who are ineligible for Medi-Cal
      (California Medicaid) and Healthy Families (its State Children's Health Insurance
      Program). A four-year evaluation of Healthy Kids finds that the program has
      improved access for more than 40,000, most of whom are immigrant Latino children,
      who have almost no access to employer coverage. However, sustaining this
      effective program has proved to be challenging.

PMID- 18332514
TI  - Rejections of drug claims for nursing home residents under Medicare Part D.
AB  - Some nursing facility administrators and physicians have raised concerns about
      the increased administrative burden of working across multiple Part D
      prescription drug plans (PDPs), citing the possibility for adverse resident
      outcomes and financial burden on facilities when PDPs reject drug claims for
      residents. We examined data on claims in rejected status for one large long-term
      care pharmacy as of December 2006. There was considerable variation across PDPs
      in both rejection rates and reasons for rejection.

PMID- 18332515
TI  - Evaluating interventions to reduce health care disparities: an RWJF program.
AB  - The Robert Wood Johnson Foundation's Finding Answers: Disparities Research for
      Change program funds evaluation of interventions to reduce racial and ethnic
      disparities in cardiovascular disease, depression, and diabetes. Of the 177
      applications received in 2006, the most prevalent proposed interventions were
      patient or provider education (57 percent), community health workers (25
      percent), case management (24 percent), integrated health care (24 percent), and
      cultural modification (24 percent). Policy interventions, including pay-for
      performance (P4P) incentives, were lacking. The eleven grantees target patients,
      providers, patient-provider communication, health care organizations, and
      communities in innovative ways. We identify important future research questions.

PMID- 18332517
TI  - Looking back at health surveys.

PMID- 18332518
TI  - Reform, then better financing.

PMID- 18332519
TI  - AHRQ and data collection.

PMID- 18332521
TI  - The uninsured and affordability.

PMID- 18332523
TI  - Protecting the veracity of practice guidelines.

PMID- 18332526
TI  - Caring about geriatric care.

PMID- 18332528
TI  - Piping a different tune.

PMID- 18332529
TI  - Self-sufficiency in a complex society.

PMID- 18332532
TI  - Integrated practice units are bridges, not 'archipelagoes'.

PMID- 18332533
TI  - Poland's nursing brain drain to the West.

PMID- 18332535
TI  - In situ surface plasmon resonance measurements of self-assembled monolayers of
      ferrocenylalkylthiols under constant potentials.
AB  - A commercial system for surface plasmon resonance (SPR) possessing a batch-type
      flow channel has been simply modified so as to conduct in situ SPR measurements
      under polarization of an Au sensor chip at constant potentials. The modified
      instrument can monitor electrochemical reactions of monolayer materials with high
      stability and high reproducibility. The redox reaction of a self-assembled
      monolayer (SAM) of 6-ferrocenyl-1-hexanethiol (FcHT) induced the resonance angle
      shifts, the magnitudes of which accorded with the Nernst equation. The
      measurements in electrolyte solutions containing different electrolyte anions
      revealed that the SPR measurements detected ion pairing of electrolyte anions
      with oxidized FcHT. In cases of measurements in alkylsulfonic acid solution,
      simulation of the results based on the N-layer model has clarified that
      alkylsulfonate anions make an assembled layer on the FcHT SAM.

PMID- 18332536
TI  - Adsorption state and morphology of anthraquinone-2-carboxylic acid deposited from
      solution onto the atomically-smooth native oxide surface of Al(111) films studied
      by infrared reflection absorption spectroscopy, X-ray photoelectron spectroscopy,
      and atomic force microscopy.
AB  - The adsorption state and morphology of anthraquinone-2-carboxylic acid (AQ-2
      COOH) deposited from acetone solutions (0.02 - 1.00 mg ml(-1)) onto atomically
      smooth native oxide surfaces of Al(111) films were investigated by infrared
      reflection absorption spectroscopy, X-ray photoelectron spectroscopy, and atomic
      force microscopy. The atomically-smooth oxide surfaces were prepared by vacuum
      evaporation of Al on mica substrates at 350 degrees C, followed by oxidation in
      an oxygen-dc glow discharge at room temperature. It was found that AQ-2-COOH is
      adsorbed on the film surfaces in both the neutral and ionized state, where the
      amount of the neutral molecules increases with increasing concentration. This
      molecule is adsorbed as both a uniform nanometer-scale film, and as micrometer
      sized particles with heights ranging from 10 to 200 nm above the film surface.
      The volumes of the particles of deposited AQ-2-COOH increased with increasing
      concentration. It is concluded that the particles are microcrystallites of
      neutral AQ-2-COOH and that the thin uniform film results from AQ-2-COOH anion
      formation on the film surfaces. A comparison of the results obtained by use of
      these surface analytical techniques clearly shows the features and advantages of
      these tools.

PMID- 18332537
TI  - Poly(methylmethacrylate) microchip electrophoresis of proteins using linear
      poly(acrylamide) solutions as separation matrix.
AB  - Poly(methylmethacrylate) (PMMA) microchip electrophoresis of sodium dodecyl
      sulfate-protein complexes (SDS-PC) using linear-poly(acrylamide) (L-PA) as a
      separation matrix was investigated. Prior to electrophoresis, channel walls of
      PMMA were modified with methylcellulose (MC) to prevent adsorption between
      channel walls and SDS-PC. Size-based protein separation (SBPS) was successfully
      performed using the MC-coated microchips with Ferguson plot-fittings. The
      entangled L-PA solution provided high resolution of peaks of SDS-PC when the
      concentration of L-PA was increased. Some investigations into the separation
      mechanism, such as the plot of the logarithm of mobility of each SDS-PC versus
      the logarithm of the molecular weight of the complex exhibiting linear behavior,
      indicated that the separation mechanism was dependent on mass discrimination, in
      accordance with Ogston model.

PMID- 18332538
TI  - Microchip electrophoresis for specific gene detection of the pathogenic bacteria
      V. cholerae by circle-to-circle amplification.
AB  - We have developed a new method for a fast and precise analysis of circle-to
      circle amplification (C2CA) product for specific gene detection by microchip
      electrophoresis. In this method, we have added a new enzymatic step to the C2CA
      reaction, which could be carried out isothermally at 37 degrees C. Compared to
      the original single-stranded DNA, the double-stranded DNA that is produced by
      this enzymatic reaction is more reliable for analysis by microchip
      electrophoresis. C2CA product was detected within 55 s with high reproducibility
      by this method which was successfully applied to the detection of 10-ng genomic
      DNA of the pathogenic bacteria Vibrio. cholerae within 110 s. Purification was
      found to be an indispensable step for the analysis of the C2CA product of genomic
      DNA samples.

PMID- 18332539
TI  - Capillary electrophoresis with laser-induced fluorescence detection as a tool for
      enzyme characterization and inhibitor screening.
AB  - An effective, rapid and economical CE/LIF (capillary electrophoresis/laser
      induced fluorescence) method was developed and applied to the characterization of
      signal peptidase (SPase) enzyme, which is a target for the screening of new drug
      candidates. In this method, CE separates the product from the substrate and LIF
      selectively detects the fluorescence-labeled product and substrate. By measuring
      the increase of the product as a function of time, one can monitor the
      progression of the enzyme reaction. The progression curves were also used for
      screening inhibitors for this enzyme. The effects of various reaction conditions
      were also studied and discussed. In addition, this CE/LIF method was applied to
      the determination of the enzyme activity, the quality control of the substrate
      and/or enzymes, and the cross-reactivity of inhibitors to the enzyme. It can be
      concluded that this method is suitable for high throughput screening (HTS) assays
      because it can deliver fast, sensitive, quantitative, and reliable results.

PMID- 18332540
TI  - Vinylferrocene homopolymer and copolymers: an electrochemical comparison.
AB  - Poly(vinylferrocene) (pVFc) homopolymer was synthesized by free radical
      polymerization, along with a series of pVFc-based copolymers containing either
      styrene, vinylanthracene or methylmethacrylate. This report details the
      electrochemical experiments conducted to examine the stability of the various
      pVFc based polymers, which is shown to be critically dependent on the extent of
      copolymerization. A trend was found that when the concentration of co-monomer was
      decreased, electrochemical stability was enhanced. Furthermore incorporation of a
      second monomer into the polymer chain produced a profound effect on the scan rate
      behaviour of the vinylferrocene moiety. As the concentration of co-monomer was
      decreased, the behaviour tended towards that of a diffusion controlled process.
      These results are of vital significance for the development of pVFc-based
      electrochemical sensors.

PMID- 18332541
TI  - Evaluation of the analytical capability of NIR femtosecond laser ablation
      inductively coupled plasma mass spectrometry.
AB  - A laser ablation-inductively coupled plasma-mass spectrometric (LA-ICPMS)
      technique utilizing a titanium-sapphire (TiS) femtosecond laser (fs-laser) has
      been developed for elemental and isotopic analysis. The signal intensity profile,
      depth of the ablation pit and level of elemental fractionation were investigated
      in order to evaluate the analytical capability of the present fs-laser ablation
      ICPMS technique. The signal intensity profile of (57)Fe, obtained from iron
      sulfide (FeS(2)), demonstrated that the resulting signal intensity of (57)Fe
      achieved by the fs-laser ablation was almost 4-times higher than that obtained by
      ArF excimer laser ablation under a similar energy fluence (5 J/cm(2)). In fs
      laser ablation, there is no significant difference in a depth of the ablation pit
      between glass and zircon material, while in ArF laser ablation, the resulting
      crater depth on the zircon crystal was almost half the level than that obtained
      for glass material. Both the thermal-induced and particle size-related elemental
      fractionations, which have been thought to be main sources of analytical error in
      the LA-ICPMS analysis, were measured on a Harvard 91500 zircon crystal. The
      resulting fractionation indexes on the (206)Pb/(238)U (f(Pb/U)) and
      (238)U/(232)Th (f(U/Th)) ratios obtained by the present fs-laser ablation system
      were significantly smaller than those obtained by a conventional ArF excimer
      laser ablation system, demonstrative of smaller elemental fractionation. Using
      the present fs-laser ablation technique, the time profile of the signal intensity
      of (56)Fe and the isotopic ratios ((57)Fe/(54)Fe and (56)Fe/(54)Fe) have been
      measured on a natural pyrite (FeS(2)) sample. Repeatability in signal intensity
      of (56)Fe achieved by the fs-laser ablation system was significantly better than
      that obtained by ArF excimer laser ablation. Moreover, the resulting precision in
      (57)Fe/(54)Fe and (56)Fe/(54)Fe ratio measurements could be improved by the fs
      laser ablation system. The data obtained here clearly demonstrate that, even with
      the fundamental wavelength (NIR operating at 780 nm), the fs-laser ablation
      system has the potential to become a significant tool for in-situ elemental and
      isotopic analysis of geochemical samples including heavy minerals and metallic
      materials.

PMID- 18332542
TI  - Effect of the chemical species of arsenic on sensitivity in graphite furnace
      atomic absorption spectrometry.
AB  - The sensitivity of graphite furnace atomic absorption spectrometry (GFAAS) to
      arsenobetaine (AB) was 1.3-times higher than to inorganic As. In order to
      understand the mechanism underlying this observation, the atomization processes
      for both chemical species were investigated in terms of the enthalpy change
      (DeltaH) during the atomization process in GFAAS. The enthalpy change of AB was
      slightly lower than that of inorganic As, which suggested that AB was atomized
      more efficiently than was inorganic As. Moreover, it was observed that some co
      existing organic materials enhanced the analytical sensitivity of inorganic As.
      The sensitivity difference between inorganic As and AB depended upon the
      mechanisms of their atomization processes.

PMID- 18332543
TI  - An optical rotatory detector for high-performance liquid chromatography using
      polarization modulation.
AB  - A sensitive and variable-wavelength optical rotatory (OR) detector for high
      performance liquid chromatography is presented. This design is entirely different
      from that of conventional OR detectors consisting of a crossed polarizer pair. By
      placing a polarizing prism and a retardation plate into a commercial circular
      dichroism (CD) detector, the OR signal was obtained. The Mueller matrix approach
      was used to prove the principle of the OR signal appearance. Sugars and 4
      androstene-3,17-dione were chosen as test compounds. The limit of detection was
      below 0.5 microg of injected sucrose at 260 nm, which was superior to that
      obtained with a conventional OR detector. For 4-androstene-3,17-dione, which is
      CD active, and shows a large anomalous OR dispersion curve, our detector gave a
      large OR signal with approximately half the intensity of the CD signal at 340 nm.

PMID- 18332544
TI  - Application of factorial design and Doehlert matrix for determination of trace
      lead in environmental samples by on-line column preconcentration FAAS using
      silica gel chemically modified with niobium(V) oxide.
AB  - In this study a new method for Pb determination in water using solid phase
      extraction coupled to a flow injection system and flame atomic absorption
      spectrometry was developed. The sorbent used for Pb preconcentration and
      extraction was silica gel chemically modified with niobium(V) oxide. Flow and
      chemical variables of the system were optimized through a multivariate procedure.
      The factors selected were buffer type, eluent concentration, and sample and
      eluent flow rates. It was verified that the aforementioned factors as well as
      their interactions were statistically significant at the 95% confidence level.
      The effect of foreign ions was evaluated using a fractionary factorial
      experimental design. The detection limit was 0.35 microg L(-1) and the precision
      was 1.6%. Results for recovery tests using different environmental samples were
      between 90 and 104%. Certified reference materials were analyzed in order to
      check the accuracy of the proposed method.

PMID- 18332545
TI  - Flow injection analysis for oxidation state speciation of vanadium(IV) and
      vanadium(V) in natural water.
AB  - A sensitive and simultaneous spectrophotometric flow injection method for the
      determination of vanadium(IV) and vanadium(V) is proposed. The method is based on
      the effect of ligands such as 2,4,6-tris(2-pyridyl)-1,3,5-triazine (TPTZ) and
      diphosphate on the conditional redox potential of iron(III)/iron(II) system. A
      four-channel flow system is assembled. In this flow system, diluted hydrochloric
      acid (1.0 x 10(-2) mol dm(-3)) as a carrier for standard/sample, acetate buffer
      (pH 5.5) as a carrier for diphosphate solution, an equimolar mixed solution of
      iron(III) and iron(II) and a TPTZ solution are delivered, so that the baseline
      absorbance can be established by forming a constant amount of iron(II)-TPTZ
      complex (lambda(max) = 593 nm). Vanadium(IV) and/or vanadium(V) (400 microL) and
      diphosphate (200 microL) solutions are simultaneously introduced into the flow
      system; in this system the diphosphate solution passes through a delay coil. The
      potential of the iron(III)/iron(II) system increases in the presence of TPTZ, and
      therefore vanadium(IV) is easily oxidized by iron(III) to vanadium(V) to produce
      an iron(II)-TPTZ complex (a positive peak for vanadium(IV) appears). On the other
      hand, the potential of the redox system decreases in the presence of diphosphate,
      so that vanadium(V) can be easily reduced by iron(II) to vanadium(IV). In this
      case, the amount of iron(II) decreases according to the amount of vanadium(V). As
      a result, the produced iron(II)-TPTZ complex decreases (a negative peak for
      vanadium(V) appears). In this manner, two peaks for vanadium(IV) and vanadium(V)
      can be alternately obtained. The limits of detection (S/N = 3) are 1.98 x 10(-7)
      and 2.97 x 10(-7) mol dm(-3) for vanadium(IV) and vanadium(V), respectively. The
      method is applied to the simultaneous determination of vanadium(IV) and
      vanadium(V) in commercial bottled mineral water samples.

PMID- 18332546
TI  - Spectrophotometric determination of plutonium in highly radioactive liquid waste
      using an internal standardization technique with neodymium(III).
AB  - A simple and rapid spectrophotometric method has been developed for the
      determination of Pu in highly radioactive liquid waste. This method uses Nd(III)
      as an internal standard, which enables us to determine the concentration of Pu
      and to authenticate the whole analytical scheme as well. A Nd(III) standard mixed
      with a sample solution and Pu was quantitatively oxidized to Pu(VI) with Ce(IV)
      in a nitric acid medium, having the maximum absorbance at 830 nm. A
      spectrophotometric measurement of Pu(VI) was subsequently performed to determine
      the concentration compared with the maximum absorbance of Nd(III) at 795 nm. It
      was estimated that the relative expanded uncertainty for a real sample is less
      than 10%. The limit of detection was calculated to be 1.8 mg/L (3 sigma). The
      proposed method was also validated through comparison experiments with isotope
      dilution mass spectrometry, and was successfully applied to analysis for nuclear
      waste management at spent nuclear fuel reprocessing plants.

PMID- 18332547
TI  - Selective preconcentration of uranyl ion by silica gel phases modified with
      chelating compounds as inorganic polymeric ion exchangers.
AB  - Four chemically modified chelating silica gel phases (I - IV) with ion exchange
      groups were tested for their potential capability to selectively bind, extract
      and preconcentrate uranyl ions (UO(2)(2+)) from different aqueous solutions as
      well as ore samples. Factors affecting such determination processes were studied
      and optimized. These included the pH of the contact solution, the mass of the
      silica gel phase extractant, the stirring time during the application of a static
      technique and the eluent concentration for desorption of the surface-bound uranyl
      ion and interfering anions and cations. All these factors were evaluated on the
      basis of determinations of the distribution coefficient value (K(d)) and the
      percent recovery (R%). Percent recovery values of 91% for silica phase (II) and
      93% for silica phase (IV) were identified in the optimum conditions. The proposed
      preconcentration method was further applied to uranium ore samples as well as
      granite samples. The determined percentage and ppm values are in good agreement
      with the standard assigned ones. The structure of the synthesized silica gel
      phases (I - IV) and their uranyl bound complexes were identified and
      characterized by means of infrared analysis, thermal analysis (TGA) and
      potentiometric titration.

PMID- 18332548
TI  - Characterization of dissolved organic matter released from Microcystis
      aeruginosa.
AB  - The contribution of dissolved organic matter (DOM) released from phytoplankton
      (Microcystis aeruginosa) during cultivation and biodegradation was examined to
      clarify the causes of the organic pollution of Lake Biwa. Two peaks, peak 2
      (retention time (RT) = 32 min) and peak 3 (RT = 35 min), were detected in the
      algal DOM released from Microcystis aeruginosa during cultivation and
      biodegradation by gel chromatography with a fluorescence detector (Ex = 340 nm,
      Em = 435 nm). As these peaks correspond with the peaks detected in the surface
      water of Lake Biwa, one can conclude that the algal DOM released from Microcystis
      aeruginosa during cultivation and biodegradation makes a considerable
      contribution to the refractory organic matter in Lake Biwa. Three fluorescence
      maxima were observed in the cultivation of Microcystis aeruginosa: a fulvic-like
      fluorescence peak (peak A) with Ex/Em values of 320/430 nm, a protein-like
      fluorescence peak (peak C) with Ex/Em values of 280/360 nm, and another peak with
      Ex/Em values of 240/370 nm. The fluorescence material of peak C has a larger MW
      than that of peak A. The algal-derived DOM from Microcystis aeruginosa has
      similar fluorescence to fulvic acid of soil origin but exhibits mainly
      hydrophilic characteristics. In the biodegradation of Microcystis aeruginosa, a
      fulvic-like fluorescence peak (peak B) with Ex/Em values of 250/440 nm and a peak
      with Ex/Em values of 320/380 nm were observed.

PMID- 18332549
TI  - Adsorption of zinc(II) and copper(II) to Shirasu (pyroclastic flow).
AB  - A fundamental study on the adsorption of metal elements on Shirasu, a pyroclastic
      flow deposit distributed in southern Kyushu, Japan, has been conducted. The
      adsorption experiment was carried out by a batch method, and by using Zn(II) and
      Cu(II) under several conditions; the effects of the initial concentration of
      metal ions, grain size, and pH were investigated. At smaller grain sizes, the
      amount of Zn(II) and Cu(II) adsorbed increased. At higher pH values, the amount
      of Zn(II) and Cu(II) adsorbed increased. Plots of the adsorption isotherm
      indicated that the adsorption of Zn(II) and Cu(II) on Shirasu followed the
      Langmuir isotherm model, and the Langmuir isotherm constants, W(0) and b, were
      obtained. W(0) at pH 5.0 was approximately two-times larger than that at pH 3.0.
      This may reflect an increase in the number of anionic binding sites on the
      surface of Shirasu with an increase in the pH. The b value for Zn hardly changed
      with an increase in the pH, and for Cu the value decreased with an increase in
      the pH. These observations suggest that anionic binding sites have a low
      stability constant, since the apparent stability constant, b, is obtained as the
      average of stability constant of all sites on the Shirasu surface.

PMID- 18332550
TI  - Reaction specificity of a titanium(IV)-porphyrin complex to hydrogen peroxide in
      view of an Ab initio study.
AB  - A Ti-TPyP reagent, i.e. an acidic aqueous solution of oxo[5,10,15,20-tetra(4
      pyridyl)porphyrinato]titanium(IV) complex, TiO(tpyp), was previously developed as
      a highly sensitive and specific reagent for determining hydrogen peroxide. In the
      present work, the reaction specificity of the TiO(tpyp) complex to hydrogen
      peroxide was clarified based on ab initio calculations. The results provide a
      well-grounded argument for determining hydrogen peroxide using the Ti-TPyP
      reagent experimentally.

PMID- 18332551
TI  - Superiority of K-edge XANES over LIII-edge XANES in the speciation of iodine in
      natural soils.
AB  - Environmental behavior of iodine is of great importance especially related to the
      release of radioiodine from the processing of nuclear fuel, nuclear accidents,
      etc. To understand the fate of radioactive iodine in soil-water systems, it is
      necessary to establish a speciation method of iodine in soil. XANES is one of the
      most important candidates and we compared the performance of L(III)-edge and K
      edge XANES for this purpose. In particular, fluorescence XANES with a multi
      element semiconductor detector is essential for the measurement of XANES spectra
      for trace amounts of iodine in natural soil samples. When comparing L(III)- and K
      edges, L(III)-edge XANES can be useful for the speciation due to its ability to
      distinguish various iodine species in their XANES spectra. However, at L(III)
      edge measuring iodine L(alpha) emission, the proximity of its energy to those of
      Ca K(alpha) and K(beta1) causes a large contribution of background X-rays in the
      XANES spectra, since Ca is a major element in soil. Thus, it was concluded that K
      edge XANES is more useful than L(III)-edge for the speciation of iodine in
      natural soils owing to its lower detection limit. The K-edge XANES was
      successfully applied to the speciation of natural iodine in a soil sample (iodine
      concentration: 55.8 mg/kg), showing that iodine is present in the sample as
      organo-iodine species incorporated in humic substances.

PMID- 18332552
TI  - Characteristic redox potential-time curve in the iron(II)/nitric acid
      autocatalytic reaction and its application to a time measurement-determination of
      folic acid.
AB  - A characteristic redox potential-time curve of the iron(II)/nitric acid
      autocatalytic reaction was applied to a time measurement-determination for sub
      microM levels of folic acid. The determination range was 7.5 x 10(-7) - 1.5 x 10(
      5) M, the detection limit (3 sigma) was 5.9 x 10(-7) M, and the relative standard
      deviation was 3.6% (n = 5).

PMID- 18332553
TI  - Potentiometric titration of polyhexamethylene biguanide hydrochloride with
      potassium poly(vinyl sulfate) solution using a cationic surfactant-selective
      electrode.
AB  - A potentiometric titration method using a cationic surfactant as an indicator
      cation and a plasticized poly(vinyl chloride) membrane electrode sensitive to the
      cationic surfactant is proposed for the determination of polyhexamethylene
      biguanide hydrochloride (PHMB-HCl), which is a cationic polyelectrolyte. A sample
      solution of PHMB-HCl containing an indicator cation (hexadecyltrimethylammonium
      ion, HTA) was titrated with a standard solution of an anionic polyelectrolyte,
      potassium poly(vinyl sulfate) (PVSK). The end-point was detected as a sharp
      potential change due to an abrupt decrease in the concentration of the indicator
      cation, HTA, which is caused by its association with PVSK. The effects of the
      concentrations of HTA ion and coexisting electrolytes in the sample solution on
      the degree of the potential change at the end-point were examined. A linear
      relationship between the concentration of PHMB-HCl and the end-point volume of
      the titrant exists in the concentration range from 2.0 x 10(-5) to 4.0 x 10(-4) M
      in the case that the concentration of HTA is 1.0 x 10(-5) M, and that from 1.0 x
      10(-6) to 1.2 x 10(-5) M in the case that the concentration of HTA is 5.0 x 10(
      6) M, respectively. The proposed method was applied to the determination of PHMB
      HCl in some contact-lens detergents.

PMID- 18332554
TI  - Evaluation of retention time for temperature-programmed gas chromatography by use
      of a closed-form integral.
AB  - A closed-form integral for the Arrhenius exponential was obtained by using an
      approximate relation instead of the usual one in a linear temperature program.
      The closed-form integral can be applied to predict the retention time very well
      both for a packed column and for a capillary column, in constant the velocity
      mode.

PMID- 18332555
TI  - Observation of oscillation in bacterial luminescence.
AB  - Oscillation in the bioluminescent intensity from a luminous bacteria suspension
      was observed. The time course of the luminescence intensity from a suspension
      containing luminous bacteria was measured. The oscillation mode changed with the
      liquid broth component. The optical density and dissolved oxygen (DO)
      concentration were measured simultaneously with the luminescence intensity, and a
      possibility was indicated that both diauxic growth and oxygen reaction
      consumption resulted with oscillation.

PMID- 18332556
TI  - Selective sequential dissolution for the determination of inorganic indium
      compounds in the particulate matter of emissions and workplace air.
AB  - A speciation method was developed for the determination of inorganic indium
      compounds in the particulate matter of emissions and from the workplace, based on
      selective sequential extractions. The main inorganic indium compounds that are
      expected to be present in the atmospheric particulate matter involving the
      industrial production of indium and in the manufacture of indium compounds were
      separated and determined. The procedure has been tested on standard reference
      materials. The indium recovery was in the range 93 - 105%.

PMID- 18332559
TI  - [Introduction; for the gerontology in actual life].

PMID- 18332560
TI  - [Aspects from the biomedical gerontology].

PMID- 18332561
TI  - [A new approach for geriatric syndrome].

PMID- 18332562
TI  - [A comment on active aging: Japanese Psychogeriatric Society].

PMID- 18332563
TI  - [A report from the position of Japanese Society of Gerodontology].

PMID- 18332564
TI  - [Perspective of social gerontology].

PMID- 18332565
TI  - [The future direction of gerontology from the perspective of life: life support
      by care management].

PMID- 18332566
TI  - [Implementation of experimental performance].

PMID- 18332567
TI  - [Quality of care among community-dwelling frail old people].

PMID- 18332568
TI  - [Dental care service for home-care elderly].

PMID- 18332569
TI  - [The basal strategy of home-care medicine for disable elderly].

PMID- 18332571
TI  - [Social supports: future directions of home care by utilization of community
      assets].

PMID- 18332570
TI  - [Rehabilitation].

PMID- 18332572
TI  - [Home care].

PMID- 18332573
TI  - [A survey on the view of end-of-life care in the elderly -a comparison among
      elderly patients, family members. physicians, nurses, and other caregivers].
AB  - AIM: The purpose of this study was to investigate the role of geriatric
      physicians in end-of-life care through surveying elderly patients, their
      families, and health-care providers including physicians, nurses, and other
      caregivers, in order to determine what comprises good end-of-life care. METHODS:
      The survey respondents comprised 148 elderly patients, 76 members of their
      families, 105 physicians, 784 nurses, and 193 other caregivers. The survey asked
      respondents to rate the importance of (a) indicators of end-of-life in the
      elderly and (b) 17 aspects of quality of end-of-life care. RESULTS: With respect
      to indicators of end-of-life in the elderly, a patient being consistently
      critically ill was rated highly by all health-care providers (>70% responded that
      this indicated end-of-life). Being unable to perform the activities of daily life
      was considered an indicator of end-of-life by 36% of patients and 45% of their
      family members, but only by 23% of physicians, 8% of nurses, and 24% of other
      caregivers. For quality of end-of-life care, four items were rated as being
      important by all groups (>70% in each group): palliation of pain, freedom from
      anxiety regarding death, ability to spend time with close friends or family, and
      being respected. However, respecting the patient's principles and lifestyle was
      thought to be less important by patients (16.1%) and family members (28.2%) than
      it was by physicians (63.8%). Death at home was also thought to be less important
      by patients (21.0%) and family members (7.1%) than by physicians (37.5%).
      CONCLUSION: Elderly patients and their families have different views from their
      health-care providers on matters related to good end-of-life care. Geriatric
      physicians should pay attention to not only the care of patients' physical needs,
      but also other needs of the patients and their families.

PMID- 18332574
TI  - [Factors burdening the caregiving relatives of community-dwelling disable
      Japanese people].
AB  - AIM: This study examined the factors associated with burdens on the primary
      caregivers of community-dwelling disabled people. METHODS: Participants were 78
      disabled people (40 men, 38 women; mean age 77.8+/-11.5 years) who received home
      based physical therapy and/or occupational therapy, and their 78 caregivers (20
      men, 58 women; mean age 66.8+/-10.2 years). The caregiver burden was assessed
      using the short version of the Japanese version of the Zarit Caregiver Burden
      Interview (J-ZBI_8). In addition, the primary caregivers completed questionnaires
      about burdens arising from supporting the activities of daily living (ADL) using
      a visual analogue scale, available social support, subjective well-being, and the
      Motor Fitness Scale. The performance of the disabled subjects was assessed using
      the Bedside Mobility Scale and the Barthel Index. The disabled subjects and the
      caregivers were divided into higher burden (J-ZBI_8 score, 10 points and over)
      and lower burden groups (J-ZBI_8 score, 9 points and under) to compare the group
      differences in the measurements. RESULTS: The disabled participants in the lower
      burden group (n=41) showed significantly higher Bedside Mobility Scale scores and
      Barthel Index scores than those in the higher burden group (n=37). The primary
      caregivers in the higher burden group showed significantly higher burden due to
      supporting the ADL, lower subjective well-being, and lower social support as
      compared to those in the lower-burden group. CONCLUSION: The burden levels of the
      primary caregivers relating to the mobility and ADL of their recipients were
      assessed. The caregivers with higher burden showed less social support and low
      subjective well-being.

PMID- 18332575
TI  - [Dementia Care Mapping-Japanese version(DCM-J) as a research evaluation method
      for measuring quality of life among elderly patients with dementia: reliability
      and validity of Well-being and Ill-being value].
AB  - AIM: Dementia Care Mapping is a behavior evaluation tool that can be used to
      measure and improve the quality of life of elderly patients with dementia.
      However, the reliability and validity of the Dementia Care Mapping-Japanese
      version (DCM-J) has not yet been established. Therefore, the purpose of this
      research was to clarify the reliability and validity of the Well-being and Ill
      being (WIB) value of the DCM-J as a method for evaluating quality of life.
      METHODS: The study was conducted from April 1, 2005 to June 30, 2006. The
      participants included 130 elderly patients (men 31, women 99, average age 82.65+/
      7.69 years) who were given a diagnosis of dementia. We established inter-rater
      reliability during a parallel observation method and also used test-retest for
      reliability. The correlation between the WIB value of the DCM-J and the Japanese
      Quality of Life Inventory for Elderly with Dementia (QOL-D) was used to establish
      criterion-related validity. RESULTS: Forty-nine (37.7%) subjects were given a
      diagnosis of dementia of Alzheimer's type, 80 (61.5%) had vascular dementia and 1
      (0.8%) had dementia with Lewy bodies. The results showed correlation between the
      WIB value and social withdrawal measured by the behavioral category code (BCC) on
      the DCM-J and the three subscales of QOL-D: "interacting with surroundings",
      "expressing self", and "experiencing minimum negative behaviors". There was good
      internal consistency among these items. The interclass correlation coefficient
      was 82.32 (+/-5.85) for the WIB value of the DCM-J. The correlation coefficient
      of the retest, administered one week later, was 0.836 (p=0.001). The WIB value
      was significantly correlated with three sub-scales of QOL-D, and the correlation
      coefficient was greater than 0.53. CONCLUSION: We demonstrated that the WIB value
      of the DCM-J has good inter-rater reliability and test re-test reliability and
      criterion-related validity. In this study, the WIB value was shown to have
      similar reliability to the WIB value of the original DCM. Furthermore, our
      results suggest that the DCM-J could be useful for evaluating quality of life
      among elderly Japanese patients with dementia.

PMID- 18332576
TI  - [Evaluation of metabolic syndrome in elderly age patients of coronary heart
      disease].
AB  - BACKGROUND: Recently, metabolic syndrome is increasing in Japan and it is thought
      to be the cause of coronary heart disease. In this study, we evaluated the
      metabolic syndrome and insulin resistance that is thought to be located in the
      upstream of metabolic syndrome in high age patients of coronary heart disease.
      PATIENTS AND METHODS: Coronary risk factors were examined and OGTT with
      measurement of plasma glucose and serum insulin was done to evaluate metabolic
      syndrome and insulin resistance in 214 patients who underwent coronary
      angiography; 102 patients were over 65 years old (high age group) and another 112
      were young age group. We compared the two groups. RESULTS: The rate of
      hypertension was significantly high and that of obesity, LDL-cholesterol level
      and triglyceride level were significantly low in high age group compared with the
      young age group. There was no difference in the ratio of metabolic syndrome
      between the two groups. The frequency of insulin resistance confirmed by HOMA-R
      was significantly high in the young age group, however there was no difference
      confirmed by 2 hour serum insulin level after OGTT. CONCLUSION: The influence of
      glucose metabolism and insulin resistance was equal between the two groups. The
      frequency of metabolic syndrome was the same, but the coronary risk factors were
      different between the two groups. Abnormal glucose metabolism and insulin
      resistance were common to both groups. To diagnose insulin resistance, 2 hour
      serum insulin level was more effective than HOMA-R.

PMID- 18332577
TI  - [Relevant factors concerning phenomena related to the process of initiating
      dialysis in elderly patients with chronic renal failure: predicting the outcomes
      of subsequent phenomena at the stage of the initial phenomenon].
AB  - AIM: We previously investigated the relevant factors concerning each individual
      phenomenon related to the process of initiating dialysis in elderly patients with
      chronic renal failure. Background factors that were identified as relevant
      factors were significant in terms of enabling us to predict the outcome of each
      phenomenon in new patients. However, the significance of these factors in
      predicting the outcomes of subsequent phenomena at the stage of the initial
      phenomenon was unclear. This was attributed to the fact that the subjects with
      phenomena decreased in number and because of changes in characteristics
      (hereafter, changes in subjects) with the progression of the process of
      initiating dialysis. In the present study, we aimed to identify relevant factors
      for predicting the outcomes of subsequent phenomena at the stage of the initial
      phenomenon. For this purpose, we assumed that "progression of the process of
      initiating dialysis does not result in significant reductions in the number of
      cases and causes only minor changes in characteristics". METHODS: We studied a
      total of 152 patients with advanced chronic renal failure aged >or=60 years.
      Background factors were investigated in all patients. The following phenomena
      were analyzed: acceptance of dialysis, urgency of initiating dialysis,
      alleviation of disease, and returning home. In order to identify new relevant
      factors, we focused on the order and condition of the process by which each
      background factor was narrowed down during logistic regression analysis for each
      phenomenon. We determined which background factor to focus on for each phenomenon
      based on changes in background factors. RESULTS: Age and cognitive function were
      related to the urgency of initiating dialysis and alleviation of disease. Age,
      walking ability, and cognitive function were related to returning home. Age was
      eliminated at the final stage of logistic regression analysis for alleviation of
      disease and at the penultimate stage of logistic regression analysis for
      returning home. CONCLUSION: We simulated the restoration of cases lost during the
      process of initiating dialysis in order to determine the relationship of age to
      alleviation of disease as well as returning home. Although age significantly
      affected alleviation of disease, its relationship to returning home was unclear.
      Age was thus identified as a new relevant factor for alleviation of disease. In
      addition, all relevant factors identified from investigation of each phenomenon
      enabled prediction of outcomes of subsequent phenomena at the stage of the
      initial phenomenon.

PMID- 18332578
TI  - [Paroxetine-induced hyponatremia in an elderly man due to the syndrome of
      inappropriate secretion of antidiuretic hormone].
AB  - We report an 82-year old man prescribed paroxetine who had hyponatremia and in
      whom the syndrome of inappropriate secretion of antidiuretic hormone was
      diagnosed. He had taken sulpiride for depressed mental status. However, he showed
      parkinsonism, which was an adverse effect from the treatment of sulpiride.
      Therefore sulpiride was changed to selective serotonin reuptake inhibitor,
      paroxetine 10mg daily. His depressed mental status deteriorated after paroxetine
      treatment started. His depression had not lessened after 12 days, and the dosage
      was increased to 20mg daily. On the 15th day after starting paroxetine, routine
      laboratory tests showed that his serum sodium level was 126 mEq/l. We recognized
      that his confusion and loss of appetite were symptoms of hyponatremia, rather
      than of worsening depression. Laboratory data revealed hyponatremia, low serum
      osmolarity (242 mOsm/kg) with a relatively high level of serum antidiuretic
      hormone, and concentrated urine (439 mOsm/kg). We diagnosed the syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH), associated with
      paroxetine. The dosage of paroxetine was reduced gradually and the serum sodium
      level returned to normal on day 2 after medication ceased completely. Paroxetine
      produces fewer adverse effects than other types of antidepressants. However, its
      use can be associated with inappropriate secretion of antidiuretic hormone in the
      body and may lead to SIADH, which is characterized by hyponatremia, a potentially
      fatal condition that is typically asymptomatic until it becomes severe. SIADH is
      more likely in some populations, including the elderly. Serum sodium levels
      should be monitored closely, especially in elderly patients.

PMID- 18332579
TI  - [A case of maternally inherited diabetes with deafness (MIDD) occurring at an
      advanced age].
AB  - We report an elderly patient with maternally inherited diabetes with deafness
      (MIDD). A 69-year-old woman was found to be diabetic for the first time when she
      visited her local medical doctor for the symptoms of a common cold. Her casual
      plasma glucose level was 311 mg/dl and HbA1c was 8.3%. She had been aware of
      muscle atrophy of the lower extremities and hearing disturbance since age 66. As
      for her family history, her mother, older sister and younger brother were
      diabetic with hearing difficulty and all of them had died suddenly in their
      middle age. Her 45-year-old daughter was also diabetic with some difficulty in
      hearing. Therefore, we suspected both the patient and her daughter had MIDD, and
      found alterations in mitochondrial DNA3243A-G. MIDD is a condition that needs to
      be diagnosed accurately and treated at an early stage, since diabetic
      complications can progress rapidly and could cause myocardial complications and
      mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes
      (MELAS). According to a report of 115 cases of MIDD in Japan, MIDD had been
      diagnosed at the age of 32.8 on average and our case was strikingly old for the
      age of onset of the disease.

PMID- 18332580
TI  - [A case of nonarteritic anterior ischemic optic neuropathy with hypertension,
      diabetes mellitus, hyperlipidemia and severe stenosis of the internal carotid
      artery].
AB  - A 76 year-old man had had hypertension, diabetes mellitus and hyperlipidemia
      since 1985, and bruit in his left neck since 1993. He had abrupt decrease in left
      visual acuity on November 24, 2005, and visited an ophthalmologist. On November
      28, his corrected visual acuity was 1.0 in the right and 0.1 in the left. The
      examination of optic fundi showed ear-side edema of the left optic disk.
      Fluorescence examination of the left optic fundus showed delay in early filling
      and later hyperfluorescence. Goldman visual field examination showed horizontal
      lower semiblindness. Since he did not complain of eye pain, his blood examination
      showed no reaction of inflammation, and he had hypertension, diabetes mellitus
      and hyperlipidemia, anterior ischemic optic neuropathy was diagnosed. The
      treatment with aspirin, alprostadil and prednisolone transiently improved the
      optic fundi and visual acuity, but his left visual acuity returned to 0.1.
      Carotid ultrasonography showed 95 percent stenosis in the left internal carotid
      artery. As there is no established treatment for ischemic optic neuropathy, the
      management of risk factors is most important.

PMID- 18332581
TI  - [A case of Creutzfeldt-Jakob disease with codon 129 polymorphism and codon 180
      point mutation].
AB  - We report a 79-year-old Japanese man with histlogically-diagnosed Creutzfeldt
      Jakob disease (CJD) with codon 129 polymorphism and codon 180 point mutation. At
      the time of the first examination, we diagnosed and treated as Alzheimer's
      disease with cerebrovascular disease because of laterality of cortex accumulation
      and an accumulation decrease of perforating branch areas at the SPECT ((123)I
      IMP). His status rapidly progressed to an apallic state and died of lung abscess
      12 months later. None of the members of his family had neuromuscular disorders.
      EEG (electroencephalogram) did not reveal periodic synchronous discharges (PSD).
      Prion protein gene analysis showed Codon 129 polymorphism (Met/Val) and codon 180
      point mutation (Val/Ile). The autopsy findings revealed spongiform changes and
      numerous senile plaque formation in the cerebral cortex. The hippocampus and the
      cerebellar cortex were well preserved and did not show lacunar infarctions. CJD
      patients with combination of the codon 180 point mutation and codon 129
      polymorphism of the PrP gene have rarely been reported.

PMID- 18332584
TI  - Quaternary pyridinium salts: a review.
AB  - Cationic surfactants are being used in various applications industrially and
      domestically for a long time. Pyridinium salts come under the category of
      cationic surfactants. These are unsaturated heterocyclic compounds having
      different functional groups present either on pyridine ring or at nitrogen atom.
      Initially, they were only considered as effective germicides. Several researches
      have been done for the modification of the properties of these salts, making them
      important for various applications. This paper reviews the types, synthesis,
      properties, and applications of quaternary pyridinium salts.

PMID- 18332585
TI  - High-melting point sediment from refined coconut oil stored in a tank for a long
      term.
AB  - A small amount of sediment occurs in refined coconut oil stored in a large-scale
      tank for a long term. This sediment is different from that generally called Cocos
      Wax, is insoluble in various organic solvents, and has an m.p. of about 100
      degrees C. In this report, we have done a structural analysis of this sediment.
      The sediment was carried out by hydrolyzing with a KOH/ethyl alcohol solution
      including toluene. Samples were analyzed by elemental analysis, IR spectroscopy,
      EI-MS, CI-MS, field desorption mass spectrometry (FD-MS), and MALDI/TOF-MS. The
      hydrolyzates were a compound including an oxo group, and its relative molecular
      mass was 382 for the acid part and 412 for the unsaponified matter according to
      EI-MS (ionization energy was 70 eV and 15 eV) and CI-MS (reagent gases were i
      butane, ammonia, and nitrogen monoxide). The relative molecular mass of the
      sediment was 1140 according to the mass spectrometry of FD, EI, and MALDI. It was
      elucidated based on the characteristic absorption analysis by IR and the
      fragmentation behavior of the EI-MS that the sediment was a wax ester, 3, 9-di-9
      oxotetradocosanecarboxy-11-oxohexacosane, consisting of an acid part of 9
      oxotetradocosanecarboxylic acid and an unsaponified matter of 3, 9-di-hydroxy-11
      oxohexacosane.

PMID- 18332586
TI  - Effect of oil-droplet size on the oxidation of microencapsulated methyl
      linoleate.
AB  - Effects of oil-droplet size, the weight ratio of oil to wall material and the
      storage temperature on the oxidation of methyl linoleate microencapsulated with
      maltodextrin by spray-drying were examined. The oxidation of methyl linoleate was
      more retarded for the microcapsules prepared from the emulsion having smaller oil
      droplets. The oxidation was more suppressed for the microcapsules having a lower
      weight ratio of oil to wall material. The fraction of unoxidized methyl linoleate
      leveled off after 10- to 15-days storage. The level, Y(infinity), depended on the
      weight ratio. The dependence of Y(infinity) on the weight ratio was analyzed
      based on the percolation theory, and the three-dimensional model of the theory
      was suitable to express the dependence. The effect of the storage temperature on
      the oxidation of microencapsulated methyl linoleate was also examined, and the
      activation energy was evaluated. The value of the energy suggested that the
      oxidation itself was a rate-limiting step for the oxidation of methyl linoleate
      encapsulated with maltodextrin.

PMID- 18332587
TI  - Supuramolecular structure of self-assembly fabricated with novel aromatic
      polyether on Si-wafers.
AB  - A new synthetic polymer of aromatic polyether (APE), having a narrow distribution
      of molecular weight, formed a specific self-assembly of Langmuir film (L film) on
      a water surface, which was subjected to surface pressure relaxation when the L
      film was compressed over 16.5 mN m(-1) at 15 degrees C. This self-assembly was
      capable of transferring on silicon-wafers as LB films. We found that, because the
      XRD patterns for fabricated LB films depended on the crystal face of the silicon
      wafer used and moreover increased in diffraction intensity with the increasing
      number of built-up layers in the LB film, the present LB films showed a kind of
      epitaxy-like phenomenon. We propose the molecular mechanism explaining that the
      formation of an ionic supuramolecular structure of APE occurs only on a silicon
      wafer surface.

PMID- 18332588
TI  - Aqueous solution properties of disulfide linked gemini and cleaved monomeric
      thiol surfactants.
AB  - Monomeric thiol surfactants, [C(n)H(2n+1)N(CH(3))(2)CH(2)CH(2)SH]Br, were
      produced by the cleavage of gemini surfactant containing a disulfide bond in the
      spacer chain,
      [C(n)H(2n+1)N(CH(3))(2)CH(2)CH(2)SSCH(2)CH(2)N(CH(3))(2)C(n)H(2n+1)]2Br. The
      disulfide bond was completely reduced by the addition of four times moles of
      dithiothreitol in water at room temperature. The critical micelle concentrations
      of monomeric surfactants were significantly increased in comparison with original
      gemini surfactants. The monomeric thiol surfactants were stable in the presence
      of dithiothreitol, whereas they returned gradually to their original gemini
      surfactants within several days due to air oxidation in water without
      dithiothreitol. The micelle formation induced by the disulfide linkage formation
      was suggested by the fluorescence intensity ratio of pyrene. The time course of
      decrease in thiol concentration associated with the recovery of gemini
      surfactants was confirmed by the absorption spectra utilizing the reactions with
      4,4'-dithiopyridine.

PMID- 18332589
TI  - Isolation and characterization of thermotolerant fungi producing lignoceric acid
      from glycerol.
AB  - In this paper, thermotolerant fungal strains which can grow on glycerol as the
      sole carbon source were isolated from soil samples. Morphological and molecular
      phylogenetic analyses of ten isolated strains showed that all strains belong to
      Aspergillus fumigatus. Analysis of their cellular fatty acid composition revealed
      that all the strains accumulated lignoceric acid (C24:0), suggesting that the
      isolated strains can be used to produce this high-value long-chain fatty acid
      from glycerol.

PMID- 18332590
TI  - Comparative study on oxidative decomposition behavior of vegetable oils and its
      correlation with iodine value using thermogravimetric analysis.
AB  - A comparative study of oxidative decomposition behavior of a wide range of
      vegetable oils and its correlation to iodine value (IV) using thermogravimetric
      analysis (TGA) was described. The oxidative decomposition of saturated fatty
      acids shows weight loss before 385 degrees C while oxidative decomposition of
      unsaturated fatty acids shows lower rate of weight loss (dWt/dt) compared to
      saturated fatty acids due to the oxidation process ('up taking ' of oxygen)
      involving breaking down of double bond to form primary and secondary oxidation
      products, which leads to some weight gain in the sample before being decomposed.
      The relative differences in the dWt/dt (%/min) of the both fatty acids give
      different decomposition steps in TGA thermogram, enabling IV to be determined
      through the percentage weight loss of saturated fatty acids per 100% of total
      sample weight (excluding weight loss from moisture and volatile compounds).
      Therefore, TGA method can be used as an alternative method for IV determination
      with no sample pre-dilution and solvent consumption. Using the TGA methods, good
      correlation (r = 0.9889) with standard AOCS method was achieved.

PMID- 18332591
TI  - Effect of a physical activity improvement program using the transtheoretical
      model at a small-scale company.
AB  - The present study aimed to investigate the potential use of the transtheoretical
      model (TTM) by clarifying the program's effects on workers at a small-scale
      company. Subjects were 22 male workers at a communication system company. They
      were divided into two physical activity improvement program groups, the TTM-based
      assistance group (TTM group, n=12) and the control group (n=10). During the study
      period each subject was asked to wear a calorie counter and to record daily
      exercise. Changes in number of steps per day and body weight were measured
      before, immediately after, and 1 month after the intervention ended. Stage of
      exercise behavior, health protective behavior, and self-efficacy were also
      examined by means of self-administered questionnaires. In the control group, the
      number of steps per day tended to increase immediately after the intervention and
      then decreased at 1 month after the program ended. In both groups, physical
      activity peaked during commuting and lunch hours. This peak persisted for 1 month
      after the intervention in the TTM group, but not in the control group. Moreover,
      the stage of exercise behavior tended to progress in the TTM group, whereas
      regression in the stage of exercise behavior was observed in the control group.
      In the control group, although the exercise self-efficacy score after
      intervention was higher than that before intervention, the health protective
      behavior score decreased at 1 month after the program ended. This study suggested
      that physical activity improvement programs based on TTM may be useful for
      workers at small-scale companies. However, further study of larger numbers of
      workers will be needed to confirm the validity and usefulness of these results.

PMID- 18332592
TI  - Angiogenesis and developmental expression of vascular endothelial growth factor
      in rat lingual papillae.
AB  - We used an embryological approach to investigate development and microvasculature
      of lingual papillae, and expression of vascular endothelial growth factor (VEGF)
      in the rat tongue. Temporal changes in the rat tongue at each developmental stage
      from embryonic day 13 (E13) to postnatal day 7 (P7) were observed by
      intravascular injection of India ink and immunohistochemistry using a VEGF
      antibody. At E13, the primordium of circumvallate papilla was observed among
      various lingual papillae. VEGF was widely expressed at E16 on the proliferated
      epithelium and the connective tissue core of circumvallate papilla. Invasion by
      capillary sprouts forming the lingual papillae was observed at E17. The
      primordium of fungiform papillae was observed at E14. VEGF was strongly expressed
      around the basal cells of proliferated epithelial tissues of fungiform papillae
      at E17. At E18, blind-ended capillary sprouts invaded into connective tissue
      cores from subepithelial sinusoidal capillaries by sprout angiogenesis. At P1,
      the invading capillary sprouts formed loops by vascular remodeling. The
      primordium of foliate papillae was observed at E16. VEGF was slightly expressed,
      but uniformly at E17 on the epithelium, muscle cells, and fibroblasts of foliate
      papillae. At E18, vascular density was increased by angiogenesis. The primordium
      of filiform papillae was observed at E17. It was the last to develop among the
      lingual papillae. VEGF was expressed in the cytoplasm of grown epithelial cells
      of filiform papillae at E19, and in blind-ended capillary sprouts formed by
      angiogenesis in the connective tissue cores at E20. The capillary sprouts formed
      loops by vascular remodeling at P1. Consequently, VEGF was expressed on the
      papillary epithelium and connective tissue cores of papillae during development
      of the papillary epithelium, and invasion by capillary sprouts into each papillae
      was observed thereafter. These results suggest a close relationship between
      expression of VEGF and angiogenesis of lingual papillae in the rat.

PMID- 18332593
TI  - GnRH agonist acts as ovarian protection in chemotherapy induced gonadotoxicity:
      an experiment using a rat model.
AB  - To reduce chemotherapy induced gonadotoxicity, co-treatment with gonadotropin
      releasing hormone against analogue (GnRHa) was tested using rat model.
      Leuprorelin acetate (Leuplin) with or without cisplatin (CDDP) was given
      subcutaneously at a dose of 9.4 microg/ml to Wistar strain female rats. The total
      number of follicles was counted and the maturation of follicles was evaluated at
      the largest section of the ovary on the 5th and 10th day after administration.
      Leuplin led the ovary to a resting phase in which primordial follicle occupied
      80% of all follicles in only 5 days after administration. The serum E2 level was
      also down by the 5th day and maintained a low level to the 10th day. In co
      treatment with GnRHa and CDDP rats, the primordial follicle occupied 90% of all
      follicles and the total number of follicles was higher than in CDDP alone rats.
      This rat model verified that GnRHa co-treatment well minimized CDDP induced
      gonadotoxocity by desensitization of the ovary. These results were promising for
      the clinical application introducing GnRHa co-treatment as ovarian protection in
      cancer chemotherapy in young women.

PMID- 18332594
TI  - Simple limbectomy dose not affect the growth of the acetabulum: an experimental
      study.
AB  - Little is known about the influence of simple limbectomy on the growth of the
      acetabulum. An experimental study was carried out in ten monkeys divided into two
      groups: limbectomy only (Group A) and limbectomy with concomitant cartilage
      resection (Group B). After three years and four months postoperatively, monkeys
      were sacrificed. Excised joints were examined macro-and microscopically.
      Degenerative changes in the cartilage and hypertrophy in the joint capsule were
      noted in all five monkeys of Group B, and in none of Group A. The diameter of the
      acetabulum was significantly enlarged in Group B (longitudinal diameter: p<0.05,
      transverse diameter: p<0.01, Mann-Whitney's U test), compared with Group A and
      the contralateral hips as controls. There was no other significant difference in
      other soft tissue or osseous components, between two groups. Histologically, the
      injured limbus was healed with irregular and sparse fibrous tissue in both
      groups. Fibrillation in the superficial layer of the cartilage and cluster
      formation was frequently noted in group B, while normal appearance was noted in
      Group A. This study demonstrated that simple limbectomy dose not affect the
      growth of the acetabulum, but may cause degenerative changes if the adjacent
      acetabular cartilage was simultaneously injured.

PMID- 18332595
TI  - Muscle maintenance by volitional contraction against applied electrical
      stimulation.
AB  - Muscle training exercises are needed for muscular endurance during spaceflight.
      This study was designed to investigate effects of volitional contraction against
      applied electrical stimulation on the muscular endurance of the proximal upper
      extremity. Thirteen healthy sedentary men were allocated into two groups. One
      group participated in a hybrid (HYB) exercise regimen in which the biceps brachii
      was stimulated as he volitionally extended his elbow, and the triceps brachii was
      stimulated as the volitionally flexed his elbow. The second group underwent a
      similar regimen in which the electrical stimulation (ELS) was alternatively
      delivered to the biceps brachii and then to the triceps brachii with the limb
      fixed. Forty-second surface electromyography (EMG) recordings at 50% maximum
      voluntary contraction (MVC) were made as baseline data at just before starting
      the training regimen, and again conclusion. The median frequency (MF) and mean
      power frequency (MPF) slopes with time were determined using power spectrum
      analysis. There were statistical significance only for the triceps in which the
      MF and MPF slopes in the HYB Group became less negative over the period of study
      (from -45.7+/-14.7 and -47.0+/-8.6%/min at baseline to -36.9+/-10.7 and -36.8+/
      7.0%/min at the end of training, respectively). The corresponding values for
      these slopes in the ELS Group showed opposite tends with less marked changes of
      borderline significance for MF and of statistical significance for MPF. These
      results suggested that the HYB exercise regimen was capable of producing an
      improvement in triceps but not biceps brachii.

PMID- 18332596
TI  - Clinicopathological study of patients undergoing resection of hilar
      cholangiocarcinoma.
AB  - Of the patients who underwent resection of hilar cholangiocarcinoma, those who
      received palliative surgery, or could not be followed up clinicopathologically,
      were excluded from this study. In the remaining 37 patients, the cumulative
      postoperative survival rate (simply referred to as the cumulative survival rate
      below) was analyzed according to gross types, histopathological parameters, final
      stages, and final curability. These patients showed a 5-year survival rate of
      17.7% and a 50% survival of 2.2 years. By gross type, patients with a localized
      papillary or nodular expansion type tended to have a better survival rate than
      those with an invasive papillary or nodular expansion type. A greater
      histological depth of invasion tended to be associated with a poorer prognosis:
      the s(-) group, that is, a group of patients without serosal exposure of cancer
      (invasion depths of m, fm, and ss) had a significantly better prognosis than the
      s(+) group, a group of patients with serosal exposure of cancer (invasion depths
      of se and si). Other histopathological parameters, such as ly, pn, pHinf, pHM,
      and pEM, were associated with significant prognostic differences. By final stage,
      the stage I/II group and stage III or higher group showed a particularly
      significant difference in prognosis. By final curability, the curability A/B
      group had a significantly better prognosis than the curability C group. Taken
      together, surgery providing curability A and B promises a good long-term
      prognosis. Therefore, it is important that efforts are made to detect cancer
      early, adequately evaluate the degree of cancer extension, and determine the
      extent of resection and the surgical technique.

PMID- 18332597
TI  - [Role of H. pylori infection in gastric cancer].

PMID- 18332598
TI  - [Endoscopic resection for early gastric cancer--JGCA gastric cancer treatment
      guidelines and indications for endoscopic resection].

PMID- 18332599
TI  - [RCT makes standardization of chemotherapy possible for advanced gastric cancers
      including outpatient-based chemotherapy].

PMID- 18332600
TI  - [Subclassification of stage IV gastric cancer].
AB  - We studied the prognosis of 185 stage IV gastric cancer cases. The univariate
      analysis and multivariate analysis suggested that liver metastases (H) and
      peritoneal disseminations (P) were prognostic factors, the number of factors may
      be it, and lymph nodes metastases (N) and invasion to the other organs (T) were
      not it. Based on these findings, we proposed a subclassification of stage IV: IVa
      [T1-3N3-or T4N2] and IVb [the others]. The survival rates for IVa significantly
      exceeded those of IVb and did not differ from those of 25 stage IIIb gastric
      cancer cases.

PMID- 18332601
TI  - [Transcatheter arterial chemoembolization (TACE) using degradable starch
      microspheres (DSM) for metastatic liver tumors in patients with gastric cancer].
AB  - We reviewed the effects and complications of transcatheter arterial
      chemoembolization (TACE), using degradable starch microspheres (DSM) in eight
      patients with hepatic metastases from gastric cancer. The rate of complete
      remission (CR) +partial remission (PR) was 62.5%, and the actual survival rates
      at one and two years post-treatment were 87.5%, and 52.5% respectively. The
      median survival time was 36.1 months. Almost all side effects were acceptable but
      in one case, we observed liver abscess. From this study, we suggest that DSM-TACE
      might be a safe and effective multimodal treatment for metastatic liver tumors in
      patients with gastric cancer.

PMID- 18332602
TI  - [Unresectable pancreatic cancer in the Hokuriku area].
AB  - To clarify the diagnosis and treatment for unresectable pancreatic cancer from
      April 2001 when gemcitabine was released, we conduct a retrospective survey in
      the Hokuriku area. We analyzed clinical data of 254 patients. Seventy-two percent
      of the patients was treated by any method, and 90.7% of those were treated with a
      protocol including gemcitabine. Gemcitabine was administered a standard protocol
      (1000 mg/m(2) for 3 consecutive weeks with one week rest) in 62.2% patients, and
      dose of gemcitabine was reduced or schedule was changed in others. The median
      survival time was 8.2 months in the therapy group, and were is no differences
      between gemcitabine monotherapy, multi-drug therapy including gemcitabine and
      radiation combining gemcitabine in survival time. Multivariable analysis clarify
      patient's age, performance status, ascites, pleural effusion, and any therapy
      were prognostic factors. This investigation revealed chemotherapy for
      unresectable pancreatic cancer with gemcitabine have been spread around the
      Hokuriku area, in addition various ways have been tried.

PMID- 18332603
TI  - [Case with diffuse duodenitis and enteritis following total colectomy for
      ulcerative colitis].
AB  - A 25-year-old-woman with four years history of pancolonic ulcerative colitis (UC)
      underwent laparoscopy-assisted restorative proctocolectomy. She developed
      postoperatively abdominal pain, high fever, bloody diarrhea. Computed tomography
      showed thickening of duodenal and small intestinal wall, and endoscopic
      examination revealed diffuse mucosal edema, redness, erosion and ulceration
      involving duodenum, small intestine and ileal pouch that was similar in
      appearance to UC. She experienced massive melena five times and was successfully
      treated by transcatheter arterial embolization. Some antibiotics and prednisolone
      failed to decrease activity of the lesion but the symptoms and endoscopic
      findings improved since intravenous dexamethasone injection.

PMID- 18332604
TI  - [Case with Todani's type Ib congenital cystic dilatation of the common bile
      duct].
AB  - A 56-year-old man, who had epigastralgia and abnormal liver function test, was
      admitted to our hospital. ERCP showed common bile duct dilation and stones. We
      therefore performed endoscopic lithotripsy after endoscopic sphincterotomy. Ten
      months later, MRCP showed recurrent CBD stones. After rehospitalization,
      resection of the dilated bile duct was carried out. This case was diagnosed
      Todani's type Ib congenital cystic dilatation of common bile duct. Todani's type
      Ib is rare type of congenital dilatation of bile duct, and is interesting
      embryologically.

PMID- 18332605
TI  - [Pedunculated carcinoid tumor of the gallbladder--analysis of the relationship
      between location and morphology in carcinoid tumor of the gallbladder].
AB  - Laparoscopic cholecystectomy was performed in a 54-year-old man because of
      gallbladder neck cancer suspected on endoscopic ultrasonography and computed
      tomography. The pathological diagnosis was carcinoid tumor of the gallbladder.
      Our case had the pedunculated morphology which was distinguishing characteristic.
      We analyzed the relationship between location and morphology in previously
      reported cases of gallbladder carcinoid tumor in Japan. The result indicated that
      carcinoid tumor of the gallbladder neck became pedunculated or subpedunculated
      more frequently than in the rectum or stomach.

PMID- 18332606
TI  - [Case of moderately differentiated hepatocellular carcinoma with gastric
      metastasis].
AB  - A solitary liver nodule about 1cm in diameter was detected in a 68-year-old male
      HBV carrier during therapy for advanced lung cancer. A multiple IIc-like
      depressed lesion originating in the stomach soon became elevated as the liver
      lesion progressed. HE staining produced hepatoma-like histological findings for
      the tumors of the lung, liver and stomach, while immunohistochemical staining
      showed them to be positive for PIVKA-II and weakly positive for HP-1. Autopsy led
      to a diagnosis of a moderately differentiated hepatocellular carcinoma producing
      bile juice with metastasis to the lung and stomach. It is not clear why advanced
      metastasis in the lung occurred while the hepatocellular carcinoma in the liver
      was still small, but one possible explanation lies in the localization of the
      hepatic cancer: the tumor was located near a branch of the hepatic vein and
      vascular invasion may have caused early pulmonary metastasis via the hepatic
      venous flow.

PMID- 18332607
TI  - [Case of pancreatic ascites successfully treated with endoscopic pancreatic
      drainage].
AB  - We report a 47-year-old man with abdominal distension without other distinct
      signs. Massive ascites with any singular lesions was revealed on computed
      tomography, and the ascites was high-amylase and high-protein. on these findings,
      pancreatic ascites was suspected and he was first treated with conservative
      therapy, but it failed. Computed tomography one month from the start of therapy
      demonstrated a pancreatic cyst, and endoscopic retrograde pancreatography
      revealed transudation of contrast medium from the cyst. A pancreatic duct stent
      was placed, and the ascites was smoothly eliminated. Endoscopic pancreatic
      stenting is considerable treatment for pancreatic ascites.

PMID- 18332608
TI  - Effects of pitavastatin on adiponectin in patients with hyperlipidemia.
AB  - The effects of treatment with pitavastatin on inflammatory and platelet
      activation markers and adiponectin in 117 patients with hyperlipidemia were
      investigated to determine whether pitavastatin may prevent the progression of
      atherosclerotic changes in hyperlipidemic patients. Adiponectin levels prior to
      pitavastatin treatment in hyperlipidemic patients with and without diabetes were
      lower than levels in normolipidemic controls. Both total cholesterol and the low
      density lipoprotein cholesterol decreased significantly after pitavastatin
      administration. Additionally, hyperlipidemic patients with or without type 2
      diabetes exhibited a significant increase in adiponectin levels 6 months after
      pitavastatin treatment (diabetes: 3.52 +/- 0.80 vs. 4.52 +/- 0.71 microg/ml, p <
      0.001; no diabetes: 3.48 +/- 0.71 vs. 4.23 +/- 0.82 microg/ml, p < 0.05).
      However, high-sensitivity C-reactive protein, platelet-derived microparticle and
      soluble P-selectin did not exhibit any differences before or after pitavastatin
      administration. Levels of adiponectin significantly increased after pitavastatin
      administration in the group of lower soluble P-selectin (soluble P-selectin
      before pitavastatin treatment <200 ng/ml). These results suggest that
      pitavastatin possesses an adiponectin-increasing effect in patients with
      hyperlipidemia and this effect is influenced by intensive platelet activation.

PMID- 18332609
TI  - Statin therapy alone and in combination with an acyl-CoA:cholesterol O
      acyltransferase inhibitor on experimental atherosclerosis.
AB  - The ability to modify the enzymatic processes involved in promoting
      atherosclerotic plaque disruption and to serially monitor atherosclerotic
      evolution could provide novel information in the management of patients with
      atherosclerosis. We studied the effects of a statin (atorvastatin) and its
      combination with an acyl-CoA:cholesterol O-acyltransferase (ACAT) inhibitor
      (avasimibe) on atherosclerotic regression and plaque stability as measured by
      matrix metalloproteinase 1 and 3 (MMP-1 and MMP-3) levels. Watanabe Heritable
      Hyperlipidemic (WHHL) rabbits treated with atorvastatin alone experienced an
      attenuated increase in atherosclerotic burden versus controls as determined by MR
      imaging. The mean vessel wall area (VWA) prior to drug therapy was 5.57 +/- 0.01
      mm2. The VWA increased to 6.71 +/- 0.03 and 7.16 +/- 0.03 mm2, respectively, in
      atorvastatin-treated and control groups (p < 0.0001 for both). The combination of
      atorvastatin and avasimibe induced a significant regression of the previously
      established atherosclerotic lesions, with the VWA decreasing to 4.54 +/- 0.04 mm2
      (p = 0.009). Atorvastatin alone induced a nonsignificant reduction in the percent
      staining of MMP-1 in atherosclerotic lesions, but the combination treatment with
      avasimibe led to a significant reduction versus controls (p = 0.005). However, a
      reduction in MMP-3 staining was significant for rabbits treated with both
      atorvastatin alone (p = 0.007) and in combination with avasimibe (p = 0.04)
      versus controls. In this animal model, the addition of avasimibe to atorvastatin
      has beneficial effects on both atherosclerotic plaque regression and
      stabilization.

PMID- 18332610
TI  - Platelet activation and red blood cell phosphatidylserine exposure evaluated by
      flow cytometry in patients with Behcet's disease: are they related to thrombotic
      events?
AB  - Behcet's disease (BD) is associated with an increased risk of venous and arterial
      thromboses that are associated with morbidity and mortality increase, although
      the mechanisms are not well established. In the present study, we used whole
      blood cytometry to determine the exposure of CD62 on the surface of platelets and
      the expression of phosphatidylserine (PS) on the surface of circulating red blood
      cells. Microparticle and microaggregate formation from platelets were also
      determined in a well-classified group of 72 patients (39 males, 33 females, aged
      46.5 +/- 12.5 years) with BD, in comparison with a well-matched control group of
      72 healthy volunteers. Results showed no differences in the above-mentioned
      parameters when BD patients and controls were compared. However, when we compared
      BD patients with/without thrombosis using these parameters, there were
      significant differences between both groups. BD patients with previous thrombosis
      had a higher percentage of circulating CD62-positive platelets and a higher
      number of circulating microaggregates than those without thrombosis, suggesting
      that platelet activation may be involved in the development of thrombotic events
      in these patients.

PMID- 18332611
TI  - Reflectance changes in clotting native blood: evidence of a red-cell process.
AB  - When broadband light illuminates clotting native blood, the reflectance at each
      wavelength traces a time course with four discernible regions. Clot formation
      occurs just before the second phase. Two wavelengths, 471 and 771 nm, were
      selected for more detailed study of the first two phases. Analysis of each time
      course in native blood demonstrates that both signals track a single process
      during the first phase, but distinct processes during the second. Experiments on
      citrated blood identified which blood components contribute to reflectance
      changes. Comparison of liquid and clotting blood reveals a single process during
      the first phase, entailing that rouleaux formation determines the time course at
      both wavelengths. Control experiments eliminate clot propagation and shape change
      of red cells or platelets as possible factors in the second phase. Exogenous ADP
      added to EDTA blood evokes the second-phase response at 471 but not 771 nm, a
      novel phenomenon that requires the presence of red cells. The descriptive name
      'ADP-end-response' is suggested for this red cell process until it is further
      characterized. We propose that the ADP-end-response determines the 471-nm signal
      during the second phase of clotting native blood and depends upon platelets in
      the absence of exogenous ADP. The 771-nm signal reports fibrin cross-linking
      during the second phase. An earlier pilot study demonstrated that rofecoxib
      effects the 471-nm signal ex vivo, which indicates that reflectance spectroscopy
      may be useful in the assessment of drug effects on platelet-erythrocyte
      interactions.

PMID- 18332612
TI  - Elevation of activated platelet-dependent chemokines and soluble cell adhesion
      molecules in patients with hematologic malignancies and high levels of beta-D
      glucan.
AB  - Most invasive fungal infections such as candidemia are frequent in patients with
      hematologic malignancies. We measured cytokines/chemokines (IL-6, IL-8, monocytic
      chemoattractant protein 1, RANTES and epithelial neutrophil-activating peptide
      78), soluble molecules (sFas, sE-selectin and soluble vascular cell adhesion
      molecule 1) and platelet activation markers (soluble CD40 ligand, sP-selectin and
      platelet-derived microparticles) in patients with hematologic malignancies under
      prophylactic treatment with an antifungal drug (fosfluconazole). We classified
      patients into 2 groups by the level of beta-D-glucan. The level of C-reactive
      protein was higher in the high beta-D-glucan group (>5 pg/ml) than in the low
      beta-D-glucan group. However, there were no differences in the levels of other
      parameters (peripheral blood cells, glutamic-oxaloacetic transaminase, glutamic
      pyruvic transaminase, lactate dehydrogenase, blood urea nitrogen and creatinine).
      Patients in the high beta-D-glucan group exhibited a significant elevation of
      several chemokines, soluble molecules and platelet activation markers compared
      with those in the low beta-D-glucan group, but the levels of IL-8, monocytic
      chemoattractant protein 1 and sFas did not differ significantly. The levels of C
      reactive protein and IL-6 increased significantly after 1 or 2 weeks on
      fosfluconazole in both groups. In contrast, the high beta-D-glucan group
      exhibited a significant decrease in chemokines, soluble markers and platelet
      derived microparticles compared with the low beta-D-glucan group after treatment
      with fosfluconazole, although the patients in the low beta-D-glucan group
      exhibited no significant changes. Furthermore, the levels of RANTES, epithelial
      neutrophil-activating peptide 78, soluble vascular cell adhesion molecule 1 and
      sE-selectin correlated positively with platelet-derived microparticles in the
      high beta-D-glucan group. These findings suggest that fungal infection may
      modulate the vascular events in which some platelet-related chemokines are
      involved.

PMID- 18332613
TI  - Reverse effect of aspirin: is the prothrombotic effect after aspirin
      discontinuation mediated by cyclooxygenase 2 inhibition?
AB  - BACKGROUND: While aspirin is the drug most often used to prevent cardiovascular
      complications, its discontinuation induces an increased risk of acute coronary
      syndrome and ischemic stroke in some patients. OBJECTIVES: We hypothesized that
      infinitesimal concentrations of aspirin could persist in plasma after its
      discontinuation, thereby inducing a prothrombotic effect that could be due to a
      modification in the mechanism of action of aspirin via the cyclooxygenase 1 (COX
      1) and COX-2 pathways. METHODS AND RESULTS: We studied the effects of ultra-low
      dose aspirin (ULDA) as well as those of sc-560 and ns-398, specific COX-1 and COX
      2 inhibitors, on induced hemorrhagic time and in a model of laser-induced
      thrombosis in rats. In the laser-induced thrombosis model, ULDA treatment
      increased the number of emboli and the duration of embolization, thereby
      confirming its prothrombotic effect described in previous publications. This
      effect was also observed in rats pretreated with sc-560 but not in those
      pretreated with ns-398. CONCLUSIONS: We demonstrated that ULDA induced a
      prothrombotic effect in the rats studied. This strongly suggests that a very
      small amount of aspirin could remain in the patient's blood after aspirin
      therapy, leading to cardiovascular complications. This effect may be mediated by
      the COX-2 pathway.

PMID- 18332614
TI  - Increased platelet cholesterol and decreased percentage volume of platelets as a
      secondary risk factor for coronary artery disease.
AB  - Platelet hyperactivity is likely to contribute to the progression of
      atherogenesis and organized thrombus formation on vascular surfaces. The purpose
      of this study was to examine the effect of hypercholesterolemia on the
      cholesterol content of platelets, on platelet responsiveness and other platelet
      indices using platelets from 5 groups of age-matched subjects (n = 30 each),
      which includes healthy controls. All groups except controls had a high plasma
      lipid profile. While subjects in group I had only hyperlipidemia, those in groups
      II and III had hyperlipidemia in conjunction with diabetes mellitus and
      hypertension, respectively. The fourth group consisted of patients with confirmed
      coronary artery disease (CAD). The parameters studied include packed cell volume
      of platelets (platelet crit), platelet distribution width (PDW), platelet
      cholesterol and platelet aggregation in response to adenosine diphosphate and
      collagen. All the patient groups showed increased platelet aggregation (p < 0.05)
      and low platelet crit compared with controls (p < 0.05). In addition, platelet
      cholesterol was increased in patients with coronary disease, hyperlipidemia and
      diabetes mellitus (p < 0.05) but not in patients with hypertension (p > 0.05);
      PDW was high only in CAD (p < 0.05). A higher PDW indicated a prothrombotic
      tendency in CAD patients. Our data suggest that hyperlipidemia increases the
      lipid content in platelets and enhances their reactivity. Hyperactive platelets
      with increased platelet cholesterol may contribute to accelerated atherogenesis
      associated with CAD.

PMID- 18332615
TI  - Interhemispheric transfer deficit in alexithymia: a transcranial magnetic
      stimulation study.
AB  - BACKGROUND: A deficit in interhemispheric transfer was hypothesized in
      alexithymia more than 30 years ago, following the observation that split-brain
      patients manifest certain alexithymic characteristics. However, direct evidence
      of interhemispheric transfer deficit has never been provided. This study
      investigated the hypothesis of a transcallosal interhemispheric transfer deficit
      in alexithymia by means of paired-pulse transcranial magnetic stimulation.
      METHODS: A random sample of 300 students was screened for alexithymia using the
      Italian version of the 20-item Toronto Alexithymia Scale. Eight right-handed
      males and eight females with high alexithymic scores and an age- and gender
      matched group with low alexithymic scores were selected. A first (conditioning)
      magnetic stimulus was delivered to one motor cortex followed by a second (test)
      stimulus to the opposite hemisphere at different interstimulus intervals for both
      motor cortices. Motor evoked responses were recorded from the abductor digit
      minimi muscles. RESULTS: High alexithymic subjects showed reduced transcallosal
      inhibition as compared to low alexithymic subjects at interstimulus intervals of
      10, 12 and 14 ms in the left-to-right and right-to-left interhemispheric transfer
      directions. CONCLUSIONS: Results point to functional differences in transcallosal
      interactions in high alexithymic as compared to low alexithymic subjects,
      supporting the hypothesis of an interhemispheric transfer deficit in alexithymia.

PMID- 18332616
TI  - Alexithymia and cognitive dysfunctions in patients with panic disorder.
AB  - BACKGROUND: In patients with panic disorder (PD), the difficulty to identify and
      manage emotional experience might contribute to the enduring vulnerability to
      panic attacks. Such a difficulty might reflect a dysfunction of fronto-temporo
      limbic circuits. The present study was designed to test the hypothesis that drug
      free patients with PD, as compared with healthy subjects (HS), show a higher
      prevalence of alexithymia, greater difficulty in emotional stimuli processing and
      poorer performance on neuropsychological tests exploring the activity of fronto
      temporo-limbic circuits. METHODS: Alexithymia, general cognitive abilities,
      focused and sustained attention, working memory, secondary memory, incidental
      learning, susceptibility to interference from both cognitive and emotional
      stimuli, and ability to recognize facial emotional expressions were assessed in
      32 drug-free patients with PD and 32 HS. RESULTS: Alexithymia was more frequent
      in patients with PD than in HS. Patients with PD, as compared to HS, had lower
      verbal cognitive abilities and more difficulty to inhibit interference from
      nonverbal stimuli and from panic-related words; they performed better than HS on
      the test assessing spatial incidental learning. Anxiety, panic symptomatology and
      verbal cognitive abilities (VIQ) were associated with alexithymia. CONCLUSIONS:
      Findings are compatible with a dysfunction of frontolimbic circuits, in
      particular orbitofrontal and cingulate cortices. A reduction in verbal cognitive
      abilities was also observed, which might suggest reduced abstraction and
      symbolization in these patients.

PMID- 18332617
TI  - Alexithymia and outcome in psychotherapy.
AB  - BACKGROUND: About 25% of all patients seeking psychotherapeutic treatment are
      considered to be alexithymic. Alexithymia has been assumed to be negatively
      associated with therapeutic outcome. On the other hand, it is unclear to which
      extent alexithymia itself may be modified by psychotherapeutic interventions.
      METHODS: From 414 consecutively admitted inpatients, 297 were followed up after 4
      weeks (t1) and after 8-12 weeks (t2) upon discharge. Patients were treated with
      psychodynamic group therapy in a naturalistic setting. The Toronto Alexithymia
      Scale (TAS-20) and the Symptom Checklist-90 were administered. RESULTS: Twenty
      seven percent of the patients were alexithymic (TAS-20 >/=61) at baseline.
      Multivariate models with repeated measurements indicated significant changes in
      Global Severity Index of the Symptom Checklist-90 in both alexithymic and
      nonalexithymic subjects. However, alexithymic subjects had significantly higher
      Global Severity Index scores than nonalexithymic subjects at t0, t1 and t2 (p <
      0.001). The TAS-20 scores demonstrated a high relative stability in the total
      sample. However, in the alexithymic group, the TAS-20 scores changed considerably
      from baseline to discharge [66.3 (SD = 4.7) to 55.9 (SD = 9.9); t = 8.69; d.f. =
      79; p < 0.001]. CONCLUSION: The inpatient treatment program including
      psychodynamic group therapy significantly reduced psychopathological distress and
      alexithymic features in alexithymic patients. Still, these patients suffered from
      higher psychopathological distress at discharge than nonalexithymics. Therefore,
      alexithymic features may negatively affect the long-term outcome.

PMID- 18332618
TI  - Plasma exchange in patients with stuporous catatonia and systemic lupus
      erythematosus.

PMID- 18332619
TI  - Pathophysiology of the pleura.
AB  - The pleural mesothelial cell is an essential cell in maintaining the normal
      homeostasis of the pleural space and it is also a central component of the
      pathophysiologic processes affecting the pleural space. In this review, we will
      review the defense mechanisms of the pleural mesothelium and changes in pleural
      physiology as a result of inflammatory, infectious, and malignant conditions with
      a focus on cytokine and chemokine networks. We will also review the processes
      involved in the pathogenesis of pleural fibrosis.

PMID- 18332620
TI  - Chronic obstructive pulmonary disease phenotyping: a possible role for 8
      isoprostane measurement in exhaled breath condensate?

PMID- 18332621
TI  - Chronic obstructive pulmonary disease: beyond the forced expiratory manoeuvre.

PMID- 18332622
TI  - Building a platform for East-West communication in stroke research: report of the
      Third International Stroke Summit, Wuhan, China, November 1-3, 2007.

PMID- 18332623
TI  - Hypoglycemia-induced pontine infarction in a diabetic male with basilar artery
      stenosis: insight into the mechanisms of hypoglycemic stroke.

PMID- 18332624
TI  - Brain haemorrhage and cerebral vasospasm associated with chronic use of cannabis
      and buprenorphine.

PMID- 18332625
TI  - Middle cerebral artery dissection gives rise to giant serpentine aneurysm.

PMID- 18332626
TI  - Choreoathetosis due to rupture of a distal accessory anterior cerebral artery
      aneurysm.

PMID- 18332627
TI  - The in vitro anti-herpes simplex virus type-1 and type-2 activity of Long Dan Xie
      Gan Tan, a prescription of traditional Chinese medicine.
AB  - BACKGROUND: Long Dan Xie Gan Tan (LDXGT), a decoction of radix gentianae for
      purging the pathogenic inflammation of the liver, is a widely used prescription
      among many in traditional Chinese medicine. The prescription is primarily used to
      treat the disorders induced by damp-heat in the liver and the gall bladder.
      METHODS: In this study, the in vitro anti-herpes simplex virus type-1 (HSV-1) and
      type-2 (HSV-2) activity of the water extract of LDXGT was investigated. RESULTS:
      LDXGT water extract was shown to exhibit anti-HSV activity. The IC(50) values of
      LDXGT against HSV-1 and HSV-2 infections were 257.5 +/- 12.2 and 494.6 +/- 1.8
      microg/ml, respectively. It had a CC(50) value of 4,077.2 +/- 2.4 microg/ml
      towards Vero cells and showed no cytotoxic effect at a concentration of 2,000
      microg/ml or below. The prescription was also found to inactivate HSV-2
      infectivity in a dose-, time- and temperature-dependent manner. CONCLUSIONS: In
      summary, the water extract of LDXGT was concluded to inhibit HSV-1 and HSV-2
      infection at different magnitudes of potency, and our observations also suggested
      that the effect was likely mediated by directly inactivating the virus
      infectivity.

PMID- 18332628
TI  - A phase I study of docetaxel and bexarotene.
AB  - BACKGROUND: We conducted a single-arm, dose-escalation, phase 1 clinical trial in
      order to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT)
      of bexarotene in combination with docetaxel. METHODS: Patients with solid tumors
      and no other curative treatment options were eligible. Oral bexarotene was taken
      daily in combination with docetaxel 25 mg/m(2) administered intravenously on days
      1, 8, and 15 of a 28-day cycle. The dose of bexarotene started at 200 mg/m(2) and
      increased by 100 mg/m(2)/dose level, until either a MTD or the final dose of 400
      mg/m(2) was reached. RESULTS: Fifteen patients were enrolled in the study. Median
      age was 58 years. The majority had non-small-cell lung cancer. The study went to
      completion without reaching an MTD. Hematological toxicities were mild. Three
      patients developed grade 3 hypertriglyceridemia, all occurring during the first
      cycle of treatment. No objective responses were noted. Four patients had stable
      disease as a best response, 3 with non-small-cell lung cancer and 1 with
      angiosarcoma. CONCLUSIONS: Treatment was well tolerated and no DLT was seen at
      docetaxel 25 mg/m(2) and bexarotene 400 mg/m(2). Given that stable disease was
      durable in 4 patients, future studies with this combination may be warranted.

PMID- 18332629
TI  - Antimicrobial activities of twenty lysine-peptoid hybrids against clinically
      relevant bacteria and fungi.
AB  - BACKGROUND: This paper describes the antimicrobial activities of 20 lysine
      peptoid hybrids against a selection of clinically relevant bacteria and fungi.
      METHODS: Minimal inhibitory concentrations were determined against methicillin
      susceptible Staphylococcus aureus (ATCC 29213), methicillin-resistant S. aureus
      (ATCC 33591), vancomycin-intermediate S. aureus (ATCC 700699 MU50), vancomycin
      resistant Enterococcus faecium (ATCC 700221), Pseudomonas aeruginosa (ATCC
      27853), Salmonella typhimurium (clinical isolate), Klebsiella pneumoniae
      (clinical isolate), amphotericin-B-resistant C. albicans (ATCC 200955) and
      Cryptococcus neoformans (clinical isolate). RESULTS: The lysine-peptoid hybrids
      proved to be active against all strains tested, except K. pneumoniae. For each
      susceptible strain, we identified at least 4 lysine-peptoid hybrids showing
      excellent activity. The most active compounds displayed minimal inhibitory
      concentrations ranging from < or =1.6 to 6.25 microM. CONCLUSION: This study
      demonstrates that lysine-peptoid hybrids show activity against drug-resistant
      pathogens.

PMID- 18332630
TI  - Survival in Alzheimer's disease is shorter in women carrying heterozygosity at
      codon 129 of the PRNP gene and no APOE epsilon 4 allele.
AB  - We assessed the role of the APOE genotype and prion protein polymorphism at codon
      129 in predicting the clinical duration of 92 neuropathologically confirmed
      sporadic Alzheimer's disease patients. Analyses of survival showed that the
      absence of the APOE epsilon 4 allele in heterozygous codon 129 PRNP carriers is a
      negative predictor of survival. When this subgroup of patients was stratified by
      sex, the effect of APOE was observed in women, but not in men.

PMID- 18332631
TI  - Severe drug hypersensitivity reaction in a young woman treated with doxycycline.
AB  - Doxycycline is a commonly prescribed medication for the management of acne
      vulgaris. Severe adverse reactions to this medication are uncommon. We describe
      an unusual case of a 20-year-old female who experienced a life-threatening
      hypersensitivity reaction, including fever, lymphadenopathy, hepatitis, nephritis
      and severe pneumonitis with respiratory failure following oral administration of
      doxycycline for facial acne.

PMID- 18332632
TI  - Cultural and language differences in voice quality perception: a preliminary
      investigation using synthesized signals.
AB  - BACKGROUND: Perceptual voice evaluation is a common clinical tool. However, to
      date, there is no consensus yet as to which common quality should be measured.
      Some available evidence shows that voice quality is a language-specific property
      which may be different across different languages. The familiarity of a language
      may affect the perception and reliability in rating voice quality. AIMS: The
      present study set out to investigate the effects of listeners' cultural and
      language backgrounds on the perception of voice qualities. METHODS AND
      PROCEDURES: Forty speech pathology students from Australia and Hong Kong were
      asked to rate the breathy and rough qualities of synthesized voice signals in
      Cantonese and English. OUTCOME AND RESULTS: Results showed that the English
      stimulus sets as a whole were rated less severely than the Cantonese stimuli by
      both groups of listeners. In addition, the male Cantonese and English breathy
      stimuli were rated differently by the Australian and Hong Kong listeners.
      CONCLUSIONS AND IMPLICATIONS: These results provided some evidence to support the
      claim that cultural and language backgrounds of the listeners would affect the
      perception for some voice quality types. Thus, the cultural and language
      backgrounds of judges should be taken into consideration in clinical voice
      evaluation.

PMID- 18332633
TI  - Mechanisms leading to increased vasodilator responses to calcitonin-gene-related
      peptide in mesenteric resistance arteries of early pregnant rats.
AB  - The objective of this study was to explore the mechanism responsible for the
      higher relaxing responses of mesenteric arteries to calcitonin-gene-related
      peptide (CGRP) in pregnancy. We performed myograph and ligand binding studies to
      determine the role of matrix metalloproteinase-2 (MMP-2) and CGRP receptor
      density. MMP activity was manipulated in isolated arteries by exposing them to
      the blocking effects of doxycycline. Vascular activity of MMP-2 was studied by
      gelatin zymography, and CGRP receptor density was determined by ligand binding
      analysis. Compared to nonpregnant rats, CGRP elicited stronger arterial
      relaxation in pregnant rats. The latter effect was neither accompanied by a
      change in relaxing responses to direct activation of adenylyl cyclase by
      forskolin nor by a change in the response to stimulation of G-protein-coupled
      adrenergic receptors by isoproterenol. Doxycycline did not affect the stronger
      arterial relaxation in pregnancy in spite of the observed more than threefold
      higher arterial MMP-2 activity. Density of binding sites for [(125)I]CGRP in
      arteries from pregnant rats (64 +/- 14 fmol/mg protein) and from virgin rats (54
      +/- 5 fmol/mg protein) were comparable. The results of this study provide
      evidence for increased coupling of CGRP receptors to adenylyl cyclase in early
      pregnancy.

PMID- 18332634
TI  - Increased matrix metalloproteinase 2 activity in the human internal mammary
      artery is associated with ageing, hypertension, diabetes and kidney dysfunction.
AB  - Dysregulation of matrix metalloproteinase (MMP)-2 in the vasculature has been
      suggested to be associated with increased prevalence of cardiovascular disease
      and renal injury. In this descriptive study, we hypothesized that arterial MMP-2
      activity is elevated in the presence of cardiovascular risk factors such as
      diabetes, hypertension, smoking and ageing, and that it correlates with the
      degree of kidney function. MMP-2 activity in internal mammary arteries (n = 37)
      was measured using gelatinolytic zymography, and cutoffs were determined using
      sample-derived medians. Patient demographics and clinical data were analyzed, and
      the estimated glomerular filtration rate (eGFR) was calculated. High MMP-2
      activity (>60,000 units) was associated with age, hypertension and diabetes (p =
      0.0034, 0.06 and 0.0034, respectively). Multivariate analysis showed that age and
      diabetes were independent predictors of high MMP-2 activity. There is a trend
      towards increased MMP-2 activity and reduced eGFR (p = 0.010). The current
      exploratory work describes that the activity of MMP-2 in the internal mammary
      artery is correlated with age, hypertension, diabetes and eGFR. It is the first
      report suggesting that MMP-2 in the arterial vasculature could be the possible
      mediator crucial in linking the progression of kidney function to cardiovascular
      disease.

PMID- 18332635
TI  - Successful use of steroids and ureteric stents in 24 patients with idiopathic
      retroperitoneal fibrosis: a retrospective study.
AB  - BACKGROUND/AIMS: Retroperitoneal fibrosis (RPF) is a chronic inflammatory
      disorder causing obstructive nephropathy and renal failure. We reviewed our
      management of this condition. METHOD: All patients with RPF treated at a single
      center over a 15-year period were identified. A full review of notes and computer
      records was undertaken. RESULTS: Data was available on 27 patients, 3 of which
      were excluded from later analysis. Diagnosis was based on clinical history and
      cross-sectional imaging. Retroperitoneal biopsy was undertaken in 3 patients. 96%
      had significant renal impairment at presentation with a mean serum creatinine of
      688 micromol/l. 46% required emergency hemodialysis. All patients were treated
      with a combination of ureteric stents and/or steroids with an excellent clinical
      response. The mean best creatinine reached by the cohort was 136 micromol/l, and
      renal function remained stable in the long term. No patients required chronic
      dialysis. Ureteric stents were removed within 12 months and low-dose steroids
      were continued for a mean of 34 months. Recurrent disease was observed in 25% of
      patients, who all responded well to further steroid therapy. Mean duration of
      follow-up was 76 months. CONCLUSIONS: RPF is very effectively treated by a
      combination of ureteric stents and steroids, with excellent long-term results
      using this approach. Continued follow-up is advised because of the possibility of
      recurrent disease.

PMID- 18332636
TI  - Mesangial proliferative glomerulonephritis with or without IgA deposits: the
      morphological characters in psoriasis vulgaris.
AB  - BACKGROUND/AIM: Chronic glomerulonephritides associated with psoriasis vulgaris
      have been reported in the literature. However, because of the limited number of
      cases and the lack of specific histological findings, the existence of psoriatic
      nephropathy remains controversial. This study was performed to investigate the
      clinical and morphological characteristics of renal involvement in psoriasis
      vulgaris. METHODS: We studied retrospectively 11 patients with psoriasis
      vulgaris. All patients had nephritic urinary sediments and underwent percutaneous
      renal biopsy between January 1997 and December 2006. To fulfill the criteria for
      the study, none of them had any other discernible chronic disease as a second
      cause of nephropathy, except for long-standing psoriasis vulgaris. RESULTS: Of
      the 11 patients, 2 (18%) had impaired renal function and 9 (82%) presented with
      hematuria. Proteinuria was noted in all patients. Their mean peak ESR was 28.3 +/
      29.1 mm/1st h. Renal biopsy specimens revealed common histological features of
      slight-to-moderate mesangial proliferative glomerulonephritis, with (73%) or
      without IgA depositions in the mesangial area. Inflammation and vascular lesions
      were unremarkable in the biopsy specimens. CONCLUSION: The results from this
      study demonstrate that mesangial proliferative glomerulonephritis with or without
      IgA deposits might be the major morphological pattern associated with psoriasis
      vulgaris.

PMID- 18332637
TI  - Influence of serum high-molecular-weight and total adiponectin on
      arteriosclerosis in IgA nephropathy patients.
AB  - BACKGROUND/AIM: Adiponectin has attracted a great deal of attention because of
      its antiatherogenic properties. Previous studies have reported that high
      molecular-weight (HMW) adiponectin may be the active form of this protein, but
      there have been no reports on the relationship between serum adiponectin and
      arteriosclerosis. The aim of our study was to determine whether HMW or total
      adiponectin levels are associated with arteriosclerosis in patients with IgA
      nephropathy. METHODS: We enrolled 72 patients aged 34.3 +/- 12.7 years, from whom
      interlobular arteries were obtained by renal biopsy in our hospital between 2003
      and 2006 and who were confirmed to have IgA nephropathy. We assessed them in
      relation to age, gender, body mass index, presence of hypertension, serum total
      cholesterol, triglyceride, uric acid, high-sensitive C-reactive protein and HMW
      adiponectin and total adiponectin levels, creatinine clearance, and urinary
      protein excretion. The severity of arteriosclerosis was semiquantitatively
      evaluated and classified into the following four grades: 0 = none; 1 = mild; 2 =
      moderate, and 3 = severe. RESULTS: Multiple stepwise regression analysis showed
      associations between arteriosclerosis grade and age [standard regression
      coefficient (st beta) = 0.560, p < 0.001], total adiponectin (st beta = -0.218, p
      = 0.026), triglyceride (st beta = 0.222, p = 0.033), and presence of hypertension
      (yes = 1, no = 0; st beta = 0.182, p = 0.036) in the IgA nephropathy patients as
      a whole and associations between arteriosclerosis grade and age (st beta = 0.708,
      p < 0.001), HMW adiponectin (st beta = -0.321, p = 0.035), and triglyceride (st
      beta = 0.292, p = 0.038) in the male IgA nephropathy patients. CONCLUSIONS: Serum
      total adiponectin levels are an independent determinant of arteriosclerosis in
      IgA nephropathy patients. It was noteworthy that in males the serum HMW
      adiponectin levels correlated more strongly with arteriosclerosis grade than the
      total adiponectin levels did. Adiponectin may prevent renal arteriosclerosis.

PMID- 18332638
TI  - Inhaled nitric oxide for the treatment of preterm infants with respiratory
      distress syndrome.
AB  - Many authors have hypothesized that inhaled nitric oxide (iNO) might acutely
      improve oxygenation in preterm neonates with infant respiratory distress syndrome
      (iRDS) and decrease the risk of bronchopulmonary dysplasia. The studies on the
      effects of iNO in preterm infants with iRDS have given contradictory results. We
      report their main methodological characteristics and the observed effects of iNO
      in preterm infants. Moreover, we discuss the infants' age at the beginning of the
      study, the dose and duration of iNO therapy, its potential effect on
      neurodevelopment, its relationship with surfactant properties, and the need to
      identify patients who are likely to respond to this therapy. We advise caution
      against the widespread use of iNO in preterm infants with iRDS. At present, it
      appears to be premature to have specific recommendations regarding the
      indications for iNO therapy in this group of patients. The conclusion of current
      trials and the follow-up studies of recently completed trials will give further
      data to guide neonatologists' decisions, and until then it is likely that
      clinicians will continue to make case-by-case decisions for the treatment of iNO
      in preterm infants with hypoxia that is unresponsive to other therapies. However,
      this decision should always be discussed with the parents.

PMID- 18332639
TI  - Cord blood prolidase activity correlates with gestational age and birth weight.
AB  - BACKGROUND: Prolidase, a specific iminopeptidase involved in collagen turnover,
      is especially active in growing tissues. OBJECTIVES: To investigate the
      relationship between cord blood prolidase activity and both birth weight and
      gestational age. METHODS: Cord blood was collected consecutively from 50 healthy
      newborns (35 term, 15 preterm). Prolidase activity was measured in the samples
      using standard methods. RESULTS: Themean +/- SD cord blood prolidase activity was
      41.4 +/- 6.9 U/l in term infants and 35.2 +/- 8.0 U/l in preterm infants and
      these were significantly different (p < 0.01). There were positive correlations
      between cord blood prolidase and both birth weight (r = 0.533, p < 0.01) and
      gestational age (r = 0.806, p < 0.01). CONCLUSION: Cord blood prolidase activity
      may be a good indicator of fetal maturation and gestational age.

PMID- 18332640
TI  - Myelin expression is altered in the brains of neonatal rats reared in a
      fluctuating oxygen atmosphere.
AB  - BACKGROUND: Preterm infants receiving supplemental oxygen therapy experience
      frequent fluctuations in their blood oxygen levels, the magnitude of which has
      been associated with the incidence and severity of retinopathy of prematurity in
      such infants. OBJECTIVE: Our objective was to investigate in a relevant animal
      model whether the immature brain with its poorly vascularised white matter might
      also be susceptible to injury when exposed to such fluctuations in blood oxygen.
      METHODS: Newborn rats were reared in an atmosphere in which a computer reproduced
      the oxygen fluctuations derived from the transcutaneous oxygen levels of a 24
      week preterm infant who had developed severe retinopathy. Following 14 days of
      exposure, we measured the expression of active caspase-3, myelin basic protein
      (MBP) and glial fibrillary acidic protein (GFAP) in the brains comparing with rat
      pups raised in room air. RESULTS: Compared to room air controls, at day 14, the
      expression of active caspase-3 was increased by up to 162% (significant increase
      in 7 of 9 regions), MBP decreased by up to 70% (significant in the hypothalamus
      only) and GFAP increased by up to 103% (significant in 6 of 7 regions. On day 21,
      following 7 days of reparative recovery, GFAP levels in most areas of oxygen
      exposed brains had returned to near control levels. There were no longer
      significant differences in caspase-3 levels apart from the cerebral cortex,
      cerebellum and striatum. In contrast, MBP expression was now much higher in most
      regions of the treated brains compared to controls. CONCLUSION: We conclude that
      fluctuations in blood oxygen, observed in preterm survivors, may constitute a
      source of injury to the white matter and corpus striatum of the developing brain
      and contribute to the neurological sequelae in extremely premature infants.

PMID- 18332641
TI  - Routine skin cultures in predicting sepsis pathogens among hospitalized preterm
      neonates in Bangladesh.
AB  - BACKGROUND: Few studies from developing countries have examined sensitivity,
      specificity, positive and negative predictive values of routine surface cultures.
      OBJECTIVES: The purpose of the study was to determine sensitivity, specificity,
      and positive predictive value (PPV) of skin cultures among preterm neonates
      admitted to Dhaka Shishu Hospital, Bangladesh. METHODS: The study was nested
      within a prospective, randomized, controlled trial of emollient treatment in
      Dhaka Shishu Hospital, Bangladesh. A total of 497 preterm infants <33 weeks
      gestational age and <72 h of chronological age were enrolled, and the
      sensitivity, specificity, and PPV of skin cultures were analyzed among 3,765
      blood-skin culture pairs, wherein the skin culture was obtained within 13 days
      before the blood culture. RESULTS: Overall sensitivity, specificity, and PPV were
      16, 38, and 5%, respectively. PPV during Klebsiella pneumoniae outbreaks was
      about 9%, and the inguinal site had the highest PPV (6%) among the three skin
      sites. Acinetobacter spp.- and K. pneumoniae-specific PPVs were 28 and 23%,
      respectively. PPV was <2% for Candida spp., Enterobacter spp., and Salmonella
      spp. CONCLUSION: Routine skin culture is inefficient in predicting the pathogen
      responsible for sepsis among premature neonates, even in a developing country
      setting, where the burden of bacterial infection is relatively high. Skin
      cultures are also of limited utility during K. pneumoniae outbreaks, and are not
      recommended.

PMID- 18332642
TI  - Effects of hyperoxia and nitric oxide on endogenous nitric oxide production in
      polymorphonuclear leukocytes.
AB  - BACKGROUND: Exposure to hyperoxia and nitric oxide (NO) occur frequently during
      the treatment of neonatal hypoxic pulmonary failure. OBJECTIVE: The aim of the
      study was to quantify the endogenous synthesis of NO in neonatal
      polymorphonuclear neutrophils following exposure to hyperoxia and NO in vitro.
      METHODS: Neonatal cord blood was exposed to room air, 25, 30 and 100% oxygen and
      10 or 20 ppm NO added to the different oxygen concentrations for up to 30 min.
      4,5-Diaminofluorescein diacetate (DAF-2 DA) is an intracellular dye used to
      measure real-time changes in NO levels in vivo. The molecular structure of DAF-2
      DA changes upon contact with NO to its oxidized and fluorescent form
      diaminofluorescein-triazol (DAF-2T) and after being hydrolyzed by intracellular
      esterases cannot leave the cell. DAF-2 DA signals following equilibration with
      room air were used as controls. RESULTS: Exposure to 100% oxygen increased NO
      production significantly when compared to 20 ppm NO plus 100% oxygen (p = 0.031)
      and to 20 ppm NO alone (p = 0.006). 10 ppm NO produced a similar effect.
      Significant increases in NO production were also noticed following exposure to
      25% oxygen. This increase was already present after 10 min of oxygen exposure.
      CONCLUSION: These findings support the propagated avoidance of hyperoxia not only
      in preterm infants, but also in term neonates.

PMID- 18332643
TI  - Oxidative stress and proinflammatory cytokine levels are increased in premature
      neonates of preeclamptic mothers with HELLP syndrome.
AB  - BACKGROUND: Respiratory distress syndrome (RDS) incidence is increased in infants
      of preeclamptic mothers with hemolysis, elevated liver enzymes, low platelets
      (HELLP) syndrome. RDS and HELLP syndrome have been associated with oxidative
      stress and inflammatory processes. OBJECTIVES: We hypothesize that end-tidal
      carbon monoxide corrected for inhaled CO (ETCOc), malondialdehyde (MDA) (markers
      of oxidative stress) and proinflammatory cytokine (IL-6, IL-8) production are
      higher in infants of preeclamptic mothers with HELLP syndrome than in those of
      preeclamptic mothers without HELLP syndrome. METHODS: Prospective study of 36
      infants of preeclamptic mothers (GA <32 weeks) admitted to the Neonatal Intensive
      Care Unit. ETCOc was measured at 0-12, 48-72 and 168 h postnatally using the CO
      Stattrade mark End-Tidal Breath Analyzer. Simultaneously, blood was sampled for
      MDA, IL-8 and IL-6. RESULTS: At 0-12 h, ETCOc, MDA and IL-8 values
      (median[range]) were significantly higher in HELLP infants than in infants from
      preeclamptic mothers without HELLP (ETCOc 2.2 [1.5-3.9] vs. 1.8 [0.5-2.9] ppm;
      MDA 2.3 [1.3-4.1] vs. 1.5 [0.4-3.1] mumol/l; IL-8 145 [24-606] vs. 62 [26-397]
      pg/ml; all p <0.05). MDA remained significantly higher during the first 168 h of
      life (2.3 [0.8-5.8] vs. 1.1 [0.8-3.7] mumol/l, p = 0.02). CONCLUSION: Oxidative
      stress and proinflammatory cytokine levels are increased in infants of
      preeclamptic mothers with HELLP syndrome. These processes may cause inactivation
      of surfactant explaining the increased RDS incidence in these infants.

PMID- 18332644
TI  - No association of TPH1 218A/C polymorphism with treatment response and
      intolerance to SSRIs in Japanese patients with major depression.
AB  - BACKGROUND: Variability in antidepressant response is due to genetic and
      environmental factors. Since SSRIs exert their activity enhancing the serotonin
      turnover, genes coding for proteins of the serotonin system are key candidates
      for a possible genetic influence with response to SSRIs. Therefore tryptophan
      hydroxylase (TPH), the rate-limiting enzyme in the biosynthesis of serotonin in
      the raphe nuclei could be a candidate. In the present study, we examined the
      possible association of the TPH1 218A/C polymorphism with response to SSRIs in a
      sample of Japanese patients with major depression. METHODS: The 21-item Hamilton
      Rating Scale for Depression (HAM-D) was administered to evaluate depressive
      symptoms at baseline and bi-weekly over 6 weeks of treatment. All patients were
      genotyped for the TPH1 218A/C polymorphism. RESULTS: Repeated-measures analysis
      of variance of HAM-D score change over time with baseline scores and 5-HTTLPR
      variants included in the model as covariate showed no significant association of
      this SNP with treatment response to SSRIs. Furthermore, no significant
      association of this SNP could be observed with both responder rate at weeks 2, 4
      and 6 and intolerance to SSRIs. CONCLUSION: The result suggests that 218A/C
      variants of TPH1 cannot play a major role as predictor of treatment response as
      well as intolerance in Japanese patients with major depression.

PMID- 18332645
TI  - Circadian variation of core body temperature in Parkinson disease patients with
      depression: a potential biological marker for depression in Parkinson disease.
AB  - BACKGROUND: The biological rhythm in comorbidity of depression and Parkinson
      disease (PD) is still unclear. For early diagnosis or clarification of the
      pathologic condition of comorbidity of depression and PD, the present study
      investigated the presence of circadian rhythm abnormalities in patients with
      depression. METHODS: We measured the rectal temperature (RT) in 30 PD patients
      with or without depression during 48 consecutive hours using the maximum entropy
      method (MEM) and least-squares method (COSINOR). The presence of major or minor
      depression was evaluated by the Mini International Neuropsychiatric Interview
      based on the 4th edition of the Diagnostic and Statistical Manual of Mental
      Disorders, and the Hamilton Depression Scale. RESULTS: The RT rhythms of patients
      without depression predominately showed a circadian rhythm. However, 2 of 6
      patients with depression showed an infradian rhythm using MEM. COSINOR revealed
      that PD patients with depression showed lower amplitudes of core body temperature
      (p = 0.012) and higher minimum RT (p = 0.031) relative to those of patients
      without depression. CONCLUSION: PD patients with depression show an altered RT
      circadian rhythm. The results suggest that the characteristics of core body
      temperature could be potentially used as a biological marker for depression in
      PD.

PMID- 18332646
TI  - Association between physical restraint and drug-induced liver injury.
AB  - OBJECTIVE: As animal models have suggested enhancement of xenobiotic-induced
      hepatotoxicity due to restraint stress, a case-control study was undertaken to
      investigate the effects of physical restraint on the development of drug-induced
      liver injury (DILI) in a psychiatric intensive care unit. METHOD: Demographic and
      clinical characteristics were compared between restrained patients (n = 106) and
      nonrestrained patients (n = 528) admitted to the psychiatric intensive care unit
      during a 4-year period from January 2003 to December 2006. RESULTS: Rates of DILI
      differed significantly between restrained patients (8.5%) and nonrestrained
      patients (1.9%; odds ratio 4.81, p = 0.0016), although no initial differences
      were seen in medical and psychiatric conditions. No differences in mean number of
      drugs were identified. The rate of patients who received antipsychotics was
      higher in the restrained group than in the nonrestrained group, whereas the rate
      of patients who received antidepressants was higher in the nonrestrained group
      than in the restrained group. CONCLUSIONS: Despite methodological limitations
      imposed by the retrospective design, a conservative claim can be made that
      physical restraint might represent a risk for DILI. This observation deserves
      confirmation in a prospective study.

PMID- 18332647
TI  - Reducing the worldwide burden of cancer.

PMID- 18332648
TI  - Salvage chemotherapy with docetaxel and epirubicin for advanced/metastatic
      gastric cancer.
AB  - BACKGROUND: We conducted a phase II study to assess the efficacy and tolerability
      of docetaxel and epirubicin as salvage chemotherapy in advanced/metastatic
      gastric cancer patients with documented progression after 5-fluorouracil/platinum
      based combination chemotherapy. METHODS: Docetaxel 75 mg/m(2) and epirubicin 50
      mg/m(2) were administered on days 1 and 2, respectively, every 3 weeks. Treatment
      continued until progression of disease or until a life-threatening adverse event
      occurred. The primary objectives of this study were to evaluate the safety
      profile and response rate to this treatment regimen. RESULTS: Thirty-four
      patients were enrolled in the study. Twenty-six patients had locally advanced or
      metastatic disease at the time of diagnosis, and 8 patients had recurrent disease
      after surgical resection of the primary tumor. A total of 157 chemotherapy cycles
      were administered. Seven (21.8%) patients had a partial response and 12 (37.5%)
      patients had stable disease. The median time to progression and overall survival
      were 4.1 and 13.4 months, respectively. Grade III/IV hematologic toxicities
      included neutropenia in 16 patients (47%) and febrile neutropenia in 8 patients
      (24%). Nonhematologic toxicities were rare. CONCLUSION: A combination of
      chemotherapy with docetaxel and epirubicin showed moderate activity as salvage
      treatment in advanced/metastatic gastric cancer, especially in patients who had
      responded to prior chemotherapy.

PMID- 18332649
TI  - Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma
      agonists in recurrent high-grade gliomas - a phase II study.
AB  - OBJECTIVES: Combined treatment approaches targeting tumor as well as other cells
      contributing to tumor progression may control chemorefractory malignancies.
      METHODS: A phase II trial was initiated to analyze the activity of continuously
      administered pioglitazone and rofecoxib combined with low-dose chemotherapy
      (capecitabine or temozolomide) in patients with high-grade gliomas (glioblastoma
      or anaplastic glioma). RESULTS: Fourteen patients were evaluable for response and
      toxicity. Major side effects were palmoplantar erythema, edema and motor
      neuropathy grade 3. Disease stabilizations lasting longer than 3 months were
      noted in 4 of 14 patients (29%). Clinical responses did not correspond to
      immunohistochemical staining for cyclooxygenase 2, peroxisome proliferator
      activated receptor-gamma and CD31. DISCUSSION: The study demonstrates that this
      novel regimen is moderately active and well tolerated in patients with high-grade
      gliomas. As a comparably small proportion of patients responded, the regimen
      might only be suitable for a subset of highly selected patients.

PMID- 18332650
TI  - Interleukin-2-based biochemotherapy for patients with stage IV melanoma: long
      term survivors outside a clinical trial setting.
AB  - BACKGROUND: The role of Interleukin-2 (IL-2)-based biochemotherapy (BCT) for
      patients with metastatic melanoma remains controversial and few data of patients
      treated outside a specialized trial setting are available. METHODS: Sixty-six
      consecutive patients treated with BCT for stage IV melanoma were analyzed
      retrospectively. All patients received BCT consisting of dacarbazine, cisplatin
      and vinblastine (CVD), interferon alfa-2a (IFN), and IL-2. IL-2 was administered
      at two different dose levels: 3 x 10(6) U/m(2)/day (BCT-3) and 9 x 10(6)
      U/m(2)/day (BCT-9), each intravenously on 4 consecutive days (days 5-8, 17-20, 26
      29). RESULTS: Nine of 66 patients achieved a complete (CR) and 11 patients a
      partial response (PR), resulting in an overall response rate of 30%. Five
      responses (2 CR and 3 PR) were observed in the 29 patients treated according to
      the BCT-3 protocol, 15 responses (7 CR and 8 PR) in the 37 patients treated
      according to the more IL-2 dose-intense BCT-9 protocol (17 vs. 41%; p = 0.033).
      Median overall survival (OS) for all 66 patients was 10 (range 3-119+) months.
      Responders had a superior OS than nonresponders (14 vs. 7 months, p < 0.001).
      After a median follow-up of 70 months, 5 patients are alive. Among them, 4 are in
      stable CR at 30+, 48+, 79+ and 119+ months, respectively, amounting to a disease
      free survival rate of 6% (4/66). CONCLUSIONS: Long-term disease-free survival for
      patients with stage IV melanoma can be achieved with BCT outside a highly
      specialized clinical trial setting. Better selection criteria are needed in order
      to avoid the unnecessary toxic treatment of the majority of patients.

PMID- 18332652
TI  - From science to action: the Lancet Series on Global Mental Health.
AB  - PURPOSE OF REVIEW: The Lancet journal has recently published a series of six
      articles on global mental health, with a focus on mental disorders in low-income
      and middle-income countries. This article provides a narrative account of the
      background to the series, its development and the key messages of these articles.
      RECENT FINDINGS: The series reports that mental disorders are so inextricably
      linked with other health concerns that there can be no health without mental
      health; mental disorders disproportionately affect the poor, and those who are
      disadvantaged and vulnerable; mental disorders are, even in the poorest countries
      of the world, a leading cause of disability and loss of economic productivity;
      low-cost treatments are feasible, affordable and effective for many mental
      disorders and these treatments can be delivered by community or general health
      workers; and the treatment gap approaches 90% even for the most severe disorders.
      SUMMARY: The series ends with a call for action to scale-up an evidence-based
      package of services for people with mental disorders, with a commitment to
      protect their human rights, and provides information on the costs, indicators and
      research strategies to support this action.

PMID- 18332653
TI  - Introduction to the forum: Is cannabis consumption a lifestyle or brain disease?

PMID- 18332654
TI  - Forum: For a balanced and integrated legislated control of cannabis.

PMID- 18332655
TI  - Forum: Decriminalization of cannabis.

PMID- 18332656
TI  - Forum: Decriminalization versus criminalization of cannabis.

PMID- 18332659
TI  - Schizophrenia today: do we know any more and can we treat it better than a decade
      ago?

PMID- 18332660
TI  - New generation antipsychotic drugs and compliance behaviour.
AB  - PURPOSE OF REVIEW: Antipsychotic therapy has been eclipsed by high rates of
      noncompliance; the problem was attributed to a lack of efficacy and the burden of
      side effects of neuroleptics. This review sought to examine whether the arrival
      of second generation (atypical) antipsychotic drugs with low side-effect
      liability and improved efficacy has helped to positively reinforce compliance
      behaviour among people treated for schizophrenia. RECENT FINDINGS: The number of
      studies that systematically examined compliance behaviour and its determinants
      during antipsychotic drug therapy is disappointingly low. A review of relevant
      clinical trials, drug dispensation databases and observational studies yielded
      equivocal results. The data have failed to substantiate the notion that novel
      antipsychotic drug use leads to improved medication compliance and favourable
      clinical outcomes. SUMMARY: A decade of clinical experience and research
      indicates that compliance behaviour has only marginally improved since the
      introduction of second generation antipsychotic drugs. Noncompliance in
      schizophrenia is a complex maladaptive pattern of behaviour determined by
      personal beliefs, illness-related factors, social attributes and health system
      variables. The reinforcing value of antipsychotic drugs may be less relevant in
      enhancing treatment compliance and influencing the natural history of
      schizophrenia.

PMID- 18332661
TI  - The effect of cannabis on the brain: can it cause brain anomalies that lead to
      increased risk for schizophrenia?
AB  - PURPOSE OF REVIEW: This review explores what is known about the association of
      cannabis with schizophrenia, its effects on the brain, and whether the brain
      changes known to be present in schizophrenia could be caused by cannabis and thus
      lead to a psychosis. RECENT FINDINGS: The heavy use of cannabis is known to be
      associated with some adverse consequences, such as the occurrence of acute
      psychotic episodes and the development of chronic schizophrenia in some people
      even after its use has terminated. Recent studies have produced controversy about
      whether cannabis in heavy use can cause irreversible brain damage, particularly
      to adolescents, and thus whether a chronic psychosis could be a result of brain
      changes caused by cannabis. SUMMARY: From the evidence that exists, it appears
      that the above view is unlikely and that cannabis may even have benign effects on
      brain structure, not producing deleterious damage. Its neurochemical interactions
      with the dopaminergic pathway, however, may, particularly in genetically
      vulnerable individuals, have adverse consequences.

PMID- 18332662
TI  - Tardive dyskinesia and new antipsychotics.
AB  - PURPOSE OF REVIEW: To provide an update on tardive dyskinesia rates in patients
      treated with first-generation or second-generation antipsychotics in studies
      published since the last systematic review in 2004. RECENT FINDINGS: Across 12
      trials (n = 28 051, age 39.7 years, 59.7% male, 70.9% white, followed for 463 925
      person-years), the annualized tardive dyskinesia incidence was 3.9% for second
      generation antipsychotics and 5.5% for first-generation antipsychotics.
      Stratified by age, annual tardive dyskinesia incidence rates were 0.35% with
      second-generation antipsychotics in children, 2.98% with second-generation
      antipsychotics versus 7.7% with first-generation antipsychotics (P < 0.0001) in
      adults, and 5.2% with second-generation antipsychotics versus 5.2% with first
      generation antipsychotics (P = 0.865) in the elderly (based almost exclusively on
      one retrospective cohort study). In four adult studies (n = 2088, age 41.2 years,
      71.2% male, 62.0% white), tardive dyskinesia prevalence rates were 13.1% for
      second-generation antipsychotics, 15.6% for antipsychotic-free patients, and
      32.4% for first-generation antipsychotics (P < 0.0001). SUMMARY: Current evidence
      supports a lower tardive dyskinesia risk for second-generation antipsychotics
      than for first-generation antipsychotics. Tardive dyskinesia incidence was higher
      with second-generation antipsychotics than previously reported, possibly due to
      recent studies with relatively short mean durations and use of nonstandard
      tardive dyskinesia definitions.

PMID- 18332663
TI  - Schizophrenia genetics: the search for a hard lead.
AB  - PURPOSE OF REVIEW: To describe the rationale for searching for genes for
      schizophrenia, prior efforts via candidate gene association and genomewide
      linkage studies, and to set the stage for the numerous genomewide association
      studies that will emerge by the end of 2008. RECENT FINDINGS: Genomewide
      association studies have identified dozens of new and previously unsuspected
      candidate genes for many biomedical disorders. At least seven new studies of
      approximately 20,000 cases plus controls are expected to be completed by the end
      of 2008. SUMMARY: Current results have few implications for clinical practice or
      research, and it is possible that this recommendation could be dramatically
      different in a year.

PMID- 18332664
TI  - Genes and structural brain imaging in schizophrenia.
AB  - PURPOSE OF REVIEW: Schizophrenia is a complex genetic disorder, caused by
      multiple genetic and environmental factors. Recently, studies have focused on
      testing specific genetic markers in a known candidate gene for association with
      endophenotypes. These are measurable characteristics of a disorder that are
      assumed to be closer to the action of the gene, resulting in higher genetic
      signal-to-noise ratios. Structural brain parameters have been shown to be useful
      endophenotypes for studies in psychiatric illnesses. RECENT FINDINGS: After
      reviewing the available studies on the influence of genotype on brain volume in
      schizophrenia, it is evident that the BDNF and COMT genes are clearly favourites
      for genetic imaging studies. Results from these studies seem to be quite
      consistent, with the same associated alleles and direction of brain volume
      changes. The most frequently investigated polymorphisms suggest that sample sizes
      of approximately 50-100 patients are sufficient to report consistent findings.
      Considering the ongoing discussion about the sample size necessary to detect
      significant associations, however, larger sample sizes are needed. SUMMARY: There
      is sufficient evidence to defend the use of structural neuroimaging as an
      endophenotype to investigate a complex phenotype such as schizophrenia despite
      the notion that, so far, no single causal pathway emerges from these studies.
      Replication studies and larger numbers of patients are essential in this respect.

PMID- 18332665
TI  - Psychoeducation in schizophrenia: new developments and approaches in the field.
AB  - PURPOSE OF REVIEW: The aim of this review is to summarize the literature on
      psychoeducation in schizophrenia published during the past year; this literature
      shows that pragmatic approaches and new adaptations have been developed. RECENT
      FINDINGS: The current literature indicates that studies on psychoeducation in
      schizophrenia in real-world settings show results comparable to those in
      experimental settings; brief psychoeducational interventions may have long-term
      effects on relapse and rehospitalization rates; and combining diagnoses may be
      helpful for new, short psychoeducational formats, but also for smaller hospitals
      with too few patients with the same diagnosis for group psychoeducation. Peer-to
      peer education programs for families and patients have been developed, and
      culturally sensitive topics, the patients' perspective, quality-of-life issues
      and sex aspects were integrated into psychoeducation. A new meta-analysis on
      psychoeducation shows that there is a medium effect size for relapse and
      rehospitalization reduction if both the patient and the family participate.
      SUMMARY: Up to the present, patient-directed approaches are much more frequent in
      clinical practice than bifocal psychoeducation. Therefore, future research must
      focus on patient-directed psychoeducation and, here especially, on integrating
      the more stable outpatients, who appear to profit more from psychoeducation than
      do symptomatic inpatients.

PMID- 18332666
TI  - Predictors of long-term outcome in schizophrenia.
AB  - PURPOSE OF REVIEW: Further clarification of factors predicting the outcome in
      schizophrenia is needed. The present review examines recent research into some of
      these predictors, focusing on insight, duration of untreated psychosis, cognition
      and early treatment response. It also addresses the need for standard outcome
      measures. RECENT FINDINGS: There is good evidence that poor insight predicts poor
      outcome, although perhaps not simply as a consequence of poor compliance. Further
      support is provided for a link between duration of untreated psychosis and long
      term outcome. The relationship between cognition and outcome is complex, with
      specific cognitive deficits apparently predicting particular outcome domains.
      Early treatment response is closely related to long-term outcome. Outcome studies
      may be flawed by sample selection bias, and a lack of standardized outcome
      measures. SUMMARY: Several predictors are potentially modifiable, indicating that
      they should be targets for therapeutic intervention. More carefully designed
      studies are needed. Recently proposed criteria for remission are helpful, and
      should facilitate cross-sample comparisons.

PMID- 18332667
TI  - Redefining (somatoform) pain disorder in ICD-10: a compromise of different
      interest groups in Germany.
AB  - PURPOSE OF REVIEW: Pain is one of the most frequent reasons to visit health
      professionals. Many patients suffering from chronic pain conditions not only need
      medical treatment but also psychiatric or psychological interventions. This
      additional treatment need should be underlined using an ICD section F diagnosis.
      The current ICD-10 diagnosis of somatoform pain disorder requests psychological
      causation of the pain, which is frequently unclear or difficult to decide. RECENT
      FINDINGS: In Germany, the different interest groups, namely of psychiatry, pain
      research, psychosomatic medicine and clinical psychology, met to find a consensus
      on how to re-classify pain disorder under section F of ICD-10. This manuscript
      summarizes the result. SUMMARY: A diagnosis of pain disorder is necessary to
      underline the additional need of psychiatric/psychological interventions in
      chronic pain conditions. This diagnosis should include psychological features
      that are relevant for development or maintenance of chronic pain. In contrast to
      earlier attempts of redefining pain diagnoses, our attempt included
      representatives of the association for the study of pain.

PMID- 18332668
TI  - Recent developments in the understanding and management of functional somatic
      symptoms in primary care.
AB  - PURPOSE OF REVIEW: Medically unexplained or functional somatic symptoms are
      prevalent in primary care, but general practitioners commonly find them difficult
      to treat. We focus on the conceptual issues and treatment from a primary care
      perspective, although the field is difficult to review because of the
      inconsistency and multiplicity of terminology used by different authors and
      specialties. RECENT FINDINGS: The training of general practitioners in management
      techniques has been hampered by an obsolete theoretical framework and outdated
      diagnostic systems. Epidemiological studies, however, indicate that valid,
      empirically based diagnostic criteria for functional disorders may be developed.
      Management studies in primary care have shown disappointing effects on patient
      outcome, but a lot may be gained by making the training programmes more
      sophisticated. Recently, stepped care approaches have been introduced but they
      need scientific evaluation. SUMMARY: There is an immediate need for a common
      language and a theoretical framework of understanding of functional symptoms and
      disorders across medical specialties, clinically and scientifically. Any names
      that presuppose a mind-body dualism (such as somatization, medically unexplained)
      ought to be abolished. The overall ambition for treatment is to offer patients
      with functional somatic symptoms the same quality of professional healthcare as
      we offer any other patient.

PMID- 18332669
TI  - Neurophysiology and psychobiology of the placebo response.
AB  - PURPOSE OF REVIEW: The placebo literature has substantially increased in 2006 and
      2007, and more and more medical and psychological subspecialties have added
      empirical data to our knowledge. RECENT FINDINGS: The theoretical framework of
      our understanding of the placebo response needs extension to account for findings
      that cannot be attributed to (Pavlovian) conditioning or suggestions alone. In
      addition, imaging studies need to address individual responses rather than group
      means, and to expand beyond experimental pain research. Gender aspects have been
      demonstrated for the placebo response but still widely ignored, especially in
      neurophysiological studies. It has been shown that nocebo research needs a
      methodological and ethical framework that allows its exploration. Finally,
      analyses of clinical trial data, either as metaanalyses or as reanalyses of trial
      raw data, may allow us to identify factors that subsequently can be used in
      experimental work. SUMMARY: Novel findings will allow better planning of clinical
      drug trials, better handling of clinical trial data in the future, and finally,
      may eventually result in improved patient management.

PMID- 18332670
TI  - Update on consultation-liaison psychiatry (psychosomatic medicine).
AB  - PURPOSE OF REVIEW: Current issues in consultation-liaison psychiatry, which is
      now labeled psychosomatic medicine as a formal subspecialty by the American Board
      of Psychiatry and Neurology, are discussed. RECENT FINDINGS: There is continued
      interest in how to best manage depression and anxiety in a primary-care setting.
      Collaborative care that utilizes a psychiatrist within the treatment center, as
      well as case management by a nurse, have been reviewed and meta-analyses suggest
      it is an efficient and effective approach. The diagnostic issues within
      psychosomatic medicine are also an area of concern as the Diagnostic and
      Statistical Manual of Mental Disorders, 5 edition, is in the planning stages. How
      to improve both the reliability and validity of somatoform disorders will be a
      major challenge. Organ transplantation is a clinical challenge for patients,
      donors and healthcare providers. Issues in assessment and management continue to
      evolve. Ethical questions also arise due to the shortage of available organs.
      SUMMARY: Psychosomatic medicine continues to manage patients in medical settings
      that cut across a continuum from primary-care to complex medical and surgical
      centers. The clinical problems containing a medical-psychiatric interface offer a
      clinical challenge but also an area for new knowledge and better interventions.

PMID- 18332671
TI  - Social and emotional support and its implication for health.
AB  - PURPOSE OF REVIEW: Recent research findings from selected publications focusing
      on links between social support and physical health are summarized. RECENT
      FINDINGS: Current research is extending our understanding of the influences of
      social support on health. Many epidemiological studies have concentrated on
      further linking measures of social support to physical health outcomes. A few
      studies are now moving into newer areas, such as emphasizing health links with
      support receipt and provision. Researchers are also interested in outlining
      relevant pathways, including potential biological (i.e. inflammation) and
      behavioral (i.e. health behaviors) mechanisms. Interventions attempting to apply
      basic research on the positive effects of social support are also widespread.
      Although the longer term effects of such interventions on physical health remain
      to be determined, such interventions show promise in influencing the quality of
      life in many chronic disease populations. SUMMARY: Recent findings often show a
      robust relationship in which social and emotional support from others can be
      protective for health. The next generation of studies must explain, however, why
      this relationship exists and the specificity of such links. This research is in
      its infancy but will be crucial in order to better tailor support interventions
      that can impact on physical health outcomes.

PMID- 18332672
TI  - New research in psychooncology.
AB  - PURPOSE OF REVIEW: The objectives of this review are to identify new studies in
      the area of psychooncology, and ascertain the directions current studies are
      taking. RECENT FINDINGS: New studies relate to the measurement of distress, which
      is being strongly proposed as the sixth vital sign in the assessment of patients
      with cancer. Attempts to use different scales and instruments to screen for
      depression and psychiatric morbidity in patients with cancer have also been made.
      Posttraumatic stress disorder, fatigue, somatization and cognitive dysfunctions
      have been studied. The field of psychoneuroimmunology has further strengthened
      our understanding of the impact of stress on immune function. Cancer survivors
      and their coping methods, sexual health, and suicidality have been the focus of
      research in the last year. Quality of life of caregivers has also been studied,
      as has spirituality. Cognitive behaviour group therapy in relatives of patients
      with cancer appears to be helpful. SUMMARY: New studies in psychooncology have
      focused on the relationship between psychosocial factors and cancer, such as
      detection of distress and psychiatric morbidity, intervention, coping methods
      used by survivors, and psychoneuroimmunology. Research in psychooncology is an
      exciting area despite numerous challenges.

PMID- 18332673
TI  - Current world literature.

PMID- 18332674
TI  - Developmental effects of 3,4-methylenedioxymethamphetamine: a review.
AB  - +/-3,4-Methylenedioxymethamphetamine (MDMA) is a chemical derivative of
      amphetamine that has become a popular drug of abuse and has been shown to deplete
      serotonin in the brains of users and animals exposed to it. To date, most studies
      have investigated the effects of MDMA on adult animals. With a majority of users
      of MDMA being young adults, the chances of the users becoming pregnant and
      exposing the fetuses to MDMA are also a concern. Evidence to date has shown that
      developmental exposure to MDMA results in learning and memory impairments in the
      Morris water maze, a task known to be sensitive to hippocampal disruption, when
      the animals are tested as adults. Developmental MDMA exposure leads to
      hypoactivity in the offspring as adults but does not affect outcome on tests of
      anxiety. MDMA administration decreases pup weight, increases corticosterone and
      brain-derived neurotrophic factor levels during treatment while decreasing brain
      levels of serotonin; a decrease that initially dissipates and then reappears in
      adulthood. Neonatal MDMA exposure increases the sensitivity of the serotonin 1A
      receptor, a possible mechanism underlying the learning and memory deficits seen.
      Taken together, the evidence shows that MDMA exposure has adverse effects on the
      developing brain and behavior. The animal and human data on developmental MDMA
      exposure are reviewed and their public health implications discussed.

PMID- 18332675
TI  - Dopamine-independent psychostimulant activity of a delta-agonist.
AB  - The effects of dopamine receptor agonists and antagonists on hyperlocomotion in
      mice induced by the nonpeptide delta-opioid receptor agonist (+)-4-[(aR)-a
      ((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N
      diethylbenzamide) (SNC80) were investigated. SNC80 significantly increased
      locomotion (maximally at 2 mg/kg). In antagonism tests, naltrindole and naltriben
      completely attenuated this SNC80-induced hyperlocomotion, which suggests that
      SNC80-induced hyperlocomotion may be mainly mediated through delta-opioid
      receptors. Although haloperidol (dopamine D2-receptor antagonist) did not affect
      SNC80-induced hyperactivity, it inhibited morphine-induced hyperlocomotion. In
      combination tests, SNC80, at a dose that did not affect spontaneous activity,
      significantly potentiated hyperlocomotion induced by methamphetamine and the
      dopamine D1-receptor agonist 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetra-hydro
      1H-3-benzazepin hydrobromide (SKF81297), whereas the combination of SNC80 and the
      D2-like receptor agonist 7-OH-N,N-di-n-propyl-2-aminotetralin did not affect
      locomotor activity. An earlier study demonstrated that the combination of the D1
      receptor agonist SKF81297 and the D2-like receptor agonist 7-OH-N,N-di-n-propyl-2
      aminotetralin synergistically induced hyperactivity in mice. Therefore, the
      present findings suggest that stimulation of either D2-like receptors or delta
      opioid receptors can enhance the hyperlocomotion induced by stimulation of D1
      receptors by methamphetamine and SKF81297, and the mechanism that underlies the
      hyperactivity caused by SNC80 may be different from that which underlies the
      effects of morphine.

PMID- 18332676
TI  - Comparative effects of olanzapine and ziprasidone on hypophagia induced by
      enhanced histamine neurotransmission in the rat.
AB  - Atypical antipsychotic drugs (AAPDs), such as olanzapine, are associated with
      weight gain and hyperphagia in both humans and rodents. This side effect,
      however, is absent or reduced for AAPD such as ziprasidone. The increased levels
      of appetite seen in rodents may be related to drug interactions with brain
      histamine systems involved in appetite control. We demonstrate a significant
      interaction of olanzapine treatment with histamine neurotransmission in a rat
      feeding paradigm measuring the consumption of a palatable fat emulsion. This
      interaction was identified using the H3 receptor antagonist thioperamide, which
      by blocking autoreceptor control of histaminergic neurons enhances release of
      hypothalamic histamine, causing hypophagia. We challenged this effect of
      thioperamide with olanzapine, which among its pharmacological actions is a potent
      H1 receptor antagonist. Olanzapine pretreatment significantly attenuated
      thioperamide-induced hypophagia. Pretreatment of thioperamide with ziprasidone,
      an AAPD with negligible H1 receptor affinity, however, failed to have this
      effect. Although thioperamide may also increase levels of neurotransmitters other
      than histamine, the potent H1 antagonist property of olanzapine is likely to
      result in the suppression of thioperamide-induced hypophagia. We conclude that
      olanzapine may be directly modulating histaminergic neurotransmission associated
      with the regulation of feeding behaviour.

PMID- 18332677
TI  - Effect of schedule of reinforcement on cue-elicited reinstatement of cocaine
      seeking behavior.
AB  - Cocaine-associated cues can elicit incentive motivational effects that drive
      cocaine-seeking behavior and contribute to relapse. The extinction/reinstatement
      model is commonly used to measure these effects in animals. This study examined
      the influence of training and testing schedules of reinforcement on cue-elicited
      reinstatement. Lever presses during training resulted in cues and cocaine (0.75
      mg/kg/IV) on either continuous or partial reinforcement schedules [fixed ratio
      (FR) 1 or 11, variable ratio (VR) 5 or 11]. Animals then underwent extinction
      training, followed by a test for cue-elicited reinstatement of extinguished
      cocaine-seeking behavior by response-contingent cue presentations on either a
      continuous (FR 1) or a partial reinforcement schedule (FR 11). Partial
      reinforcement during training resulted in higher response rates during cue
      elicited reinstatement relative to continuous reinforcement. In contrast,
      delivery of cues on a continuous reinforcement schedule during testing yielded
      higher response rates relative to delivery on a partial reinforcement schedule.
      Finally, the shift from a partial to a continuous reinforcement schedule across
      training and testing phases did not alter response rates. These findings provide
      important information for choosing parameters for reinstatement of drug-seeking
      behavior that would allow the most sensitive method to detect changes in response
      rate after an experimental manipulation.

PMID- 18332678
TI  - Effects of reversible inactivation of the dorsal hippocampus on the behavioral
      and cardiovascular responses to an aversive conditioned context.
AB  - In rats, conditioned fear to context causes freezing immobility and
      cardiovascular changes. The dorsal hippocampus (DH) has a critical role in
      several memory processes, including conditioning fear to contextual information.
      To explore a possible involvement of the DH in contextual fear conditioning
      evoked cardiovascular (mean arterial pressure and heart rate increases) and
      behavioral (freezing) responses, DH synaptic transmission was temporarily
      inhibited by bilateral microinjections of 500 nl of the nonselective synapse
      blocker, cobalt chloride (CoCl2, 1 mmol/l), at different periods of the
      experimental procedure. During re-exposure to the foot shock chamber in which
      conditioning had taken place, bilateral DH inhibition 10 min before the
      conditioning session had no effect on either behavioral or cardiovascular
      responses. Bilateral DH inhibition immediately after the conditioning session (10
      min) decreased both behavioral and cardiovascular responses during the context
      test. Finally, 48 h after the conditioning session, bilateral DH inhibition 10
      min before re-exposure to the foot shock chamber significantly reduced
      cardiovascular responses but not freezing responses. These results suggest that
      contextual fear conditioning acquisition does not depend on the DH. This
      structure, however, is crucial for the consolidation of contextual fear.
      Moreover, although the DH appears to be less important for the behavioral
      (freezing) changes induced by re-exposure to the aversive conditioned context, it
      may play an important role on the cardiovascular responses generated by this
      model.

PMID- 18332679
TI  - Effects of antipsychotics and reference monoaminergic ligands on marble burying
      behavior in mice.
AB  - Antipsychotics constitute efficacious augmenting agents in the treatment of
      anxiety disorders, including refractory obsessive-compulsive disorder. We
      examined the effects of 36 compounds, including typical, atypical and novel
      antipsychotics with dual dopamine D2/5-hydroxytryptamine 1A (D2/5-HT1A) actions
      on marble burying behavior in mice, a putative preclinical test for anxiety
      disorders. One hour after drug administration, male NMRI mice were placed
      individually in cages containing 20 marbles, and the total number of marbles
      buried after 30 min was counted. The selective serotonin reuptake inhibitors,
      citalopram (2.5-40 mg/kg), fluoxetine (2.5-10 mg/kg) and the benzodiazepine
      diazepam (2.5-10 mg/kg), reduced the number of buried marbles. The atypical
      antipsychotic, clozapine (0.16-10 mg/kg), but not its congener olanzapine, was
      effective in this test. Haloperidol, a typical antipsychotic, also reduced the
      number of buried marbles, albeit not in a dose-dependent manner. The atypical
      risperidone was partially active (0.16-0.63 mg/kg), as was the benzamide
      derivative, amisulpride, albeit at high (10-40 mg/kg) doses. Among the 'third
      generation' antipsychotics possessing combined D2/5-HT1A properties, bifeprunox
      was active at 0.0025 mg/kg, whereas SLV313 and aripiprazole were active only at
      the highest doses (2.5 and 10 mg/kg, respectively). SSR181507, F15063 and the
      antidyskinetic agent, sarizotan, were without any effect. Among a series of
      receptor subtype-selective ligands, only the 5-HT1A agonist, (+)-8-OH-DPAT (0.63
      2.5 mg/kg) and the 5-HT2A/2B/2C antagonist, ritanserin (0.63-2.5 mg/kg) were
      active. Among novel antipsychotics with dual D2/5-HT1A properties, only
      bifeprunox was able to potently reduce the number of buried marbles. Inhibition
      of marble burying behavior may result from the interplay of several receptor
      systems, including 5-HT2 receptor blockade, dopamine D2 partial agonism and
      serotonin 5-HT1A agonism.

PMID- 18332680
TI  - Effects of SB-269970, a 5-HT7 receptor antagonist, in mouse models predictive of
      antipsychotic-like activity.
AB  - 5-HT7 receptors have been linked to a number of psychiatric disorders including
      anxiety and depression. The localization of 5-HT7 receptors in the thalamus, a
      key sensory processing center, and the high affinity of many atypical
      antipsychotic compounds for these receptors have led to the speculation of the
      utility of 5-HT7 antagonists in schizophrenia. The goal of these studies was to
      examine the effects of pharmacologic blockade and genetic ablation of 5-HT7
      receptors in animal models predictive of antipsychotic-like activity. We
      evaluated the effects of SB-269970, a selective 5-HT7 receptor antagonist, on
      amphetamine and ketamine-induced hyperactivity and prepulse inhibition (PPI)
      deficits. In addition, sensorimotor gating function and locomotor activity were
      evaluated in 5-HT7 knockout mice. Locomotor activity was measured for up to 180
      min using an automated infrared photobeam system, and PPI was evaluated in
      startle chambers. SB-269970 (3, 10 and 30 mg/kg, intraperitoneally) significantly
      blocked amphetamine [3 mg/kg, subcutaneously (s.c.)] and ketamine (30 mg/kg,
      s.c.)-induced hyperactivity and reversed amphetamine (10 mg/kg, s.c.)-induced but
      not ketamine (30 mg/kg, s.c.)-induced PPI deficits, without changing spontaneous
      locomotor activity and startle amplitude. The largest dose of SB-269970 did not
      block the effects of amphetamine in 5-HT7 knockout mice. Collectively, these
      results indicate that blockade of 5-HT7 receptors partially modulates
      glutamatergic and dopaminergic function and could be clinically useful for the
      treatment of positive symptoms of schizophrenia.

PMID- 18332681
TI  - Acute and rebound effects of lorazepam on orolingual motor function in young
      versus aged Fischer 344/Brown Norway rats.
AB  - The purpose of this study was to measure the acute effects of lorazepam [a short
      acting benzodiazepine (BZ) with no active metabolites] on orolingual motor
      function in young (6 months) versus aged (24 months) Fischer 344/Brown Norway
      hybrid (F344/BN) rats. Rats licked water from an isometric force-sensing
      operandum so that the number of licks per session, licking rhythm (licks/second),
      and lick force could be measured during daily sessions. Acute doses (1.0 and 2.0
      mg/kg) of lorazepam were administered 30 min before the testing sessions, 4 days
      apart. Whereas aged rats produced more licks per session, lorazepam increased
      this measure primarily in the young group. On the days after each lorazepam dose,
      rats licked less than they did before receiving the drug. This effect was shown
      by both groups. Aged rats showed significantly slower licking rhythm than young
      rats. Lorazepam slowed this measure in both groups. Peak tongue forces were
      significantly increased by lorazepam. These findings suggest that BZs such as
      lorazepam can affect tongue force output and exacerbate age-related tongue
      motility deficits. They also suggest that although BZs can directly influence
      motivation to engage in water-reinforced tasks, opposite 'rebound' effects may
      occur, even after acute dosing.

PMID- 18332682
TI  - Influence of thyroid hormones on 3,4-methylenedioxymethamphetamine-induced
      thermogenesis and reinforcing strength in monkeys.
AB  - In monkeys, elevating ambient temperature has been shown to increase sensitivity
      to 3,4-methylenedioxymethamphetamine (MDMA) reinforcement. Earlier rodent studies
      have shown that elevations in thyroid levels (hyperthyroidism) parallel changes
      in elevating the ambient temperature on MDMA-induced thermogenesis, but the
      interaction has not been examined in monkeys. This study was designed to evaluate
      the effects of chronic levothyroxine (3.0 or 4.5 microg/kg/day, intramuscularly;
      Levo) treatment on MDMA-induced increases in body temperature following 1.5 mg/kg
      (intravenously) MDMA and self-administration when MDMA (0.03-0.3 mg/kg/injection)
      and food were available under a concurrent fixed-ratio 30 schedule of
      reinforcement in rhesus monkeys (n=4). Earlier studies had shown that 1.5 mg/kg
      MDMA did not affect thermoregulation at 24 degrees C. Chronic Levo treatment
      resulted in significant increases in MDMA-induced thermogenesis. In the self
      administration experiment, MDMA choice increased with dose, such that food was
      preferred over saline and a low MDMA dose (0.03 mg/kg/injection), whereas 0.1 and
      0.3 mg/kg/injection MDMA was preferred over food. Although elevating ambient
      temperature had been shown to increase MDMA potency, there was no effect of
      chronic Levo treatment on MDMA choice. These results suggest that changes in
      thyroxine levels do not parallel the changes in ambient temperature in altering
      the reinforcing strength of MDMA.

PMID- 18332683
TI  - Specialist status: holy grail, poisoned chalice, or flat cola?

PMID- 18332684
TI  - Statement of the Second International Exercise-Associated Hyponatremia Consensus
      Development Conference, New Zealand, 2007.

PMID- 18332685
TI  - IOC consensus statement on training the elite child athlete.

PMID- 18332686
TI  - Functional performance deficits in patients with CAI: validity of the multiple
      hop test.
AB  - OBJECTIVES: To investigate the reliability and validity of a functional
      performance test in patients with chronic ankle instability (CAI). DESIGN: Cross
      sectional study. SETTING: All tests were conducted in the practice room of the
      physical therapy department of the Vrije Universiteit Brussel. PARTICIPANTS:
      Twenty-nine healthy subjects and 29 patients with CAI were selected. For the main
      outcome measurements, participants performed a multiple hop test two times,
      within a 1-week time interval. Subjects hopped on 10 different tape markers and
      had to try to avoid making any postural correction. Only when subjects stood
      still were they allowed to continue hopping. The time needed to complete the test
      and VAS scores for the perceived difficulty were assessed. RESULTS: In unstable
      ankles, ICCs of time values were >0.90 (SEM = 2.3 seconds); Spearman rho values
      of VAS scores were >0.80. When hopping on their unstable ankles, patients (41.1
      +/- 12.6 seconds) needed significantly more time to complete the test than
      healthy subjects (31.4 +/- 5.0 seconds; test: P = 0.000; retest: P = 0.002) or
      when compared with their unaffected contralateral ankles (38.0 +/- 7.1 seconds;
      test: P = 0.047; retest: P = 0.009). Only with respect to the dominant ankles,
      patients (median = 64 mm) perceived the test as significantly more difficult than
      did healthy subjects (median = 37 mm; test: P = 0.018; retest: P = 0.002). VAS
      scores of unstable ankles in patients (median = 50 mm) were significantly higher
      than their contralateral, unaffected ankles (median = 30 mm; test: P = 0.001;
      retest: P = 0.002). CONCLUSIONS: The multiple hop test is a reliable test
      demonstrating functional performance deficits in patients with CAI.

PMID- 18332687
TI  - Scapular muscular activity with shoulder impingement syndrome during lowering of
      the arms.
AB  - OBJECTIVE: To compare isolated electromyographic (EMG) activity of the serratus
      anterior, upper, middle, and lower trapezius, as well as the coactivation of the
      upper and middle trapezius/serratus anterior in subjects with and without
      shoulder impingement syndrome (IS), during lowering of the arms. DESIGN: Cross
      sectional study. SETTING: University laboratory. PARTICIPANTS: Twenty young
      adults, 10 with unilateral IS degree I or II (mean age 28.6 +/- 5.89 years) and
      10 without any complaints or history of previous shoulder lesions (mean age 29.0
      +/- 5.35 years), matched by gender, age, and levels of physical activity. MAIN
      OUTCOME MEASUREMENTS: Isolated EMG activity of the serratus anterior, upper,
      middle, and lower trapezius, as well as the coactivation of the upper trapezius
      and middle trapezius/serratus anterior. The EMG activity was quantified by root
      mean square calculations and normalized by maximal voluntary isometric
      contractions. RESULTS: Significant differences between groups were found only for
      the coactivation of the middle trapezius/serratus anterior (F = 6.81; P = 0.02).
      No significant differences were found between sides (F = 0.05; P = 0.83) nor for
      interactions between sides and groups (F = 3.85; P = 0.07). CONCLUSIONS: These
      findings pointed out the importance of evaluating the lowering of the arms in
      individuals with IS and suggested that measures of coactivation, besides
      reflecting the real purpose of the muscular actions during functional activities,
      are more sensitive to detect changes between groups. The evaluation of the
      coactivation of the middle trapezius/serratus anterior should be included in
      clinical assessment of individuals with IS and investigations on the etiology and
      progression of IS.

PMID- 18332688
TI  - Incidence and characteristics of time-loss injuries in competitive fencing: a
      prospective, 5-year study of national competitions.
AB  - OBJECTIVE: To estimate the incidence of time-loss injuries in competitive fencing
      and to characterize these injuries regarding type and location. DESIGN: A 5-year
      prospective study. SETTING: Data were collected at all national events organized
      by the U.S. Fencing Association (USFA) during the 2001-2006 seasons.
      PARTICIPANTS: A total of 78,223 male and female competitors, ranging in age from
      8 to above 70, participated in various events in the targeted competitions.
      METHODS: Experienced certified athletic trainers (ATC) evaluated and documented
      all incidents that resulted in withdrawal from competition. Exposure data
      [athlete exposures (AE)] were calculated from the number of bouts completed in
      each competition. MAIN OUTCOME MEASURES: Rate of time-loss injury was calculated
      per 1000AE. Frequency distributions for types and locations of injuries were used
      to characterize time-loss injuries. RESULTS: One hundred eighty-four time-loss
      injuries were reported during the study, for an overall rate of 0.3 per 1000 AE
      (95% CI: 0.26-0.35). Of these, 26.1% were recorded as strains and 25.5% were
      identified as sprains. The knee was the most frequently injured location (19.6%),
      followed by the thigh (15.2%) and the ankle (13%). Overall, 60% of the injuries
      were in the lower extremities. CONCLUSIONS: The rate of time-loss injury in
      competitive fencing is low. Although there are differences in the distribution of
      types and location of time-loss injuries by sex and discipline, the predominant
      characteristics (sprain/strain in the lower extremities) are similar to other
      sports with ballistic action in stop-start, rapid change-of-direction activity.

PMID- 18332689
TI  - Declared use of medication in sports.
AB  - OBJECTIVE: To assess and compare the prevalence of declared medication, such as
      corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), beta2-agonists,
      narcotic analgesics, anaesthetics, and antidepressant drugs, in time and between
      different sports among athletes tested for doping control in a 4-year period.
      DESIGN: Survey study. SETTING: Belgium. PARTICIPANTS: This paper reviews the data
      obtained from 18,645 doping control forms gathered between 2002 and 2005 from
      national doping organisations in Belgium and The Netherlands, the International
      Cycling Union (UCI), and the Belgian Cycling Federation. INTERVENTION: All
      athletes were asked by doping control officers to declare the medication taken in
      the last 3 days before competition after which the doping control forms were
      double blinded and handed over to the laboratory. MAIN OUTCOME MEASUREMENTS:
      Classification of declared medication according to the active ingredient.
      RESULTS: The overall declared use of medication belonging to one of the monitored
      categories increased from 19.8% in 2002 to 24.67% in 2005. Differences in use of
      medication were observed between sports with a higher prevalence of use of NSAIDs
      in ball sports compared to other sports and a higher use of beta-agonists and
      corticosteroids in cycling with percentages of declared corticosteroid use in
      samples from the UCI exceeding 36% in 2005. CONCLUSION: These results indicate
      that the current granting of therapeutic use exemption for corticosteroids and
      beta-agonists needs to be revised and that threshold levels for beta-agonists
      should be implemented.

PMID- 18332690
TI  - Reliable change of the sensory organization test.
AB  - OBJECTIVE: To establish the sensitivity and specificity of the NeuroCom Sensory
      Organization Test (SOT) and provide practitioners with cut-scores for clinical
      decision making using estimates of reliable change. DESIGN: Retrospective cohort
      study. SETTING: Research laboratory. PATIENTS: Healthy (n = 66) and concussed (n
      = 63) young adult participants. INTERVENTIONS: Postural control assessments on
      the NeuroCom SOT were completed twice (baseline and follow-up) for both groups.
      Postconcussion assessments were administered within 24 hours of injury diagnosis.
      MAIN OUTCOME MEASUREMENTS: The reliable change technique was used to calculated
      cut-scores for each SOT variable (composite balance; somatosensory, visual, and
      vestibular ratios) at the 95%, 90%, 85%, 80%, 75%, and 70% confidence interval
      levels. RESULTS: When cut-scores were applied to the post-concussion evaluations,
      sensitivity and specificity varied with SOT variable and confidence interval. An
      evaluation for change on one or more SOT variable resulted in the highest
      combined sensitivity (57%) and specificity (80%) at the 75% confidence interval.
      CONCLUSIONS: Use of reliable change scores to detect significant changes in
      performance on the SOT resulted in decreased sensitivity and improved specificity
      compared to a previous report. These findings indicate that some concussed
      athletes may not show large changes in postconcussion postural control and this
      postural control evaluation should not be used in exclusion of other assessment
      techniques. The postural control assessment should be combined with other
      evaluative measures to gain the highest sensitivity to concussive injuries.

PMID- 18332691
TI  - Athletic performance and serial weight changes during 12- and 24-hour ultra
      marathons.
AB  - OBJECTIVE: The principal objective of this study was to evaluate serial weight
      changes in athletes during 12- and 24-hour ultra-marathons and to correlate these
      changes with athletic performance, namely the distance covered. DESIGN: This was
      a prospective study. SETTING: The 2003 Soochow University international ultra
      marathon. PARTICIPANTS: Fifty-two race participants. INTERVENTIONS: 12- or 24
      hour ultra-marathon. MAIN OUTCOME MEASUREMENTS: Body weight changes were measured
      before, at 4-hour intervals during, and immediately after the 12- and 24-hour
      races. RESULTS: Significant overall decreases in body weight were apparent at the
      conclusion of both races. The mean relative body weight change after the 12-hour
      race was -2.89 +/- 1.56%, ranging from 0 to 6.5%. The mean relative body weight
      change after the 24-hour race was -5.05 +/- 2.28%, ranging from -0.77% to 
      11.40%. Of runners in the 24-hour race, 26% lost greater than 7% of baseline body
      weight during the race. During both the 12- and 24-hour races, the greatest
      weight change (decrease) occurred during the first 4 hours. Weight remained
      relatively stable after 8 hours, although a further decrease was apparent between
      16 and 20 hours in the 24-hour participants. Weight change had no bearing on
      performance in the 12-hour race, whereas weight loss was positively associated
      with performance in the 24-hour race. CONCLUSIONS: Our findings demonstrate that
      the majority of weight decrease/dehydration in both the 12- and 24-hour races
      occurred during the first 8 hours. Hence, to maintain body weight, fluid intake
      should be optimized in the first 8 hours for both 12- and 24-hour runners and in
      16 to 20 hours for 24-hour marathon runners.

PMID- 18332692
TI  - Vitamin D status of females in an elite gymnastics program.
AB  - OBJECTIVE: Vitamin D plays an important role in calcium and bone metabolism. In
      Australia it has been assumed that all young athletes have good vitamin D levels.
      A survey of females in an elite gymnastics program was undertaken to determine
      their vitamin D and dietary calcium status. DESIGN: Cross-sectional survey.
      SETTING: Females in an elite gymnastics program at the Australian Institute of
      Sport. PARTICIPANTS AND OUTCOME MEASURES: Eighteen female gymnasts aged 10-17
      years were assessed for vitamin D status (serum 25[OH]D) and dietary calcium
      intake. RESULTS: Fifteen were found to have levels below current recommended
      guidelines for optimal bone health (<75 nmol/L). Six had vitamin D levels below
      50 nmol/L. Thirteen of the gymnasts also had daily dietary calcium intakes below
      the daily recommended intake for their age. CONCLUSIONS: Gymnasts and possibly
      other indoor athletes should be carefully reviewed for vitamin D and calcium
      status.

PMID- 18332693
TI  - Practical management of grade III acromioclavicular separations.
AB  - Acromioclavicular joint (AC) injuries are common in the young athletic
      population. There is general agreement that grade I and grade II separations are
      best managed nonoperatively, whereas grades IV to VI warrant surgical
      stabilization. In contrast, considerable controversy exists surrounding the best
      method of treatment for grade III AC separations. The trend in recent literature
      is toward the initial nonoperative management of these injuries. However,
      consideration of other factors such as type of sport, timing of injury relative
      to athletic season, or the throwing demands in an injured dominant arm may play a
      role in the decision to treat grade III injuries operatively or nonoperatively.
      We offer a protocol algorithm for treating grade III AC separations for managing
      this controversial injury.

PMID- 18332694
TI  - Acute avulsion of the fibrocartilage origin of the adductor longus in
      professional soccer players: a report of two cases.

PMID- 18332695
TI  - Recurrent tachycardia-induced cardiomyopathy in an elite soccer player.

PMID- 18332696
TI  - Hemoglobin mass in an elite endurance athlete before, during, and after injury
      related immobility.

PMID- 18332697
TI  - Staphylococcus aureus septicemia secondary to hand abrasions in a professional
      hockey player--a case report.

PMID- 18332698
TI  - Fitness and cardiovascular events in asymptomatic men and women.

PMID- 18332699
TI  - Precooling improves endurance performance in the heat.

PMID- 18332700
TI  - Do wrist guards decrease injuries among snowboarders?

PMID- 18332701
TI  - Does bracing after ACL reconstruction improve outcomes?

PMID- 18332703
TI  - Advancements in neonatal intensive care (almost) ready for prime time.

PMID- 18332704
TI  - Continuous positive airway pressure: scientific and clinical rationale.
AB  - PURPOSE OF REVIEW: To present recent data on the role of noninvasive ventilation
      in the respiratory management of newborn infants. RECENT FINDINGS: Noninvasive
      ventilation is growing in popularity but is applied using widely varying devices
      and settings. Although short-term physiological advantages were reported for
      bubble and variable-flow continuous positive airways pressure, neither has
      convincingly shown superior clinically important outcomes. Continuous positive
      airways pressure may be used as the initial mode of support for very preterm
      infants but increased rates of pneumothorax in infants not receiving surfactant
      are a concern. Methods of administering surfactant without endotracheal
      intubation deserve further study. Nasal intermittent positive-pressure
      ventilation shows promise as a primary treatment for respiratory distress
      syndrome. Optimal pressure settings for continuous positive airways pressure and
      nasal intermittent positive-pressure ventilation remain uncertain. SUMMARY:
      Noninvasive ventilation has partially fulfilled its promise as a gentler
      alternative to ventilation via an endotracheal tube. Appropriately designed
      randomized clinical trials are required to determine the best nasal interfaces
      and pressure generators.

PMID- 18332705
TI  - Methods and evidence on volume-targeted ventilation in preterm infants.
AB  - PURPOSE OF REVIEW: Several modalities of volume-targeted ventilation have been
      developed for the premature infant or were adopted from those used in older
      populations. The article describes these modalities, their clinical application
      in preterm infants and reviews the evidence for the possible beneficial effects
      in this population. RECENT FINDINGS: Evidence from physiologic studies indicates
      increased stability of tidal volume and gas exchange while requiring less
      ventilatory support. Randomized trials of volume-targeted ventilation indicate
      faster weaning and shorter duration of mechanical ventilation, but this has not
      resulted in better respiratory outcome. SUMMARY: The proposed benefits of volume
      targeted ventilation on respiratory outcome have not been fully confirmed by the
      existing data. Some trends suggest possible benefits, but these need to be
      further explored. The efficacy of volume-targeted ventilation may be method
      dependent and may also be influenced by the magnitude of the volume targeted.

PMID- 18332706
TI  - Is the early and aggressive administration of protein to very low birth weight
      infants safe and efficacious?
AB  - PURPOSE OF REVIEW: Most conventionally managed very low birth weight infants
      experience postnatal growth restriction. There is some evidence that this
      postnatal growth restriction may have long-lasting effects, and contribute to
      short stature and poor neurodevelopmental outcomes. There is also evidence
      suggesting that early protein intake may improve growth in these very low birth
      weight infants. Therefore, to optimize protein intake early in the infant's
      neonatal course seems a logical goal. RECENT FINDINGS: Randomized controlled
      trials provide evidence of short-term safety and efficacy for starting amino acid
      infusion as soon as possible after birth at 2.5-3.0 g/kg/day in very low birth
      weight infants; however, there are no long-term data to support the safety or
      efficacy of this practice. There is some evidence from recent studies of improved
      growth by providing 4.0 g/kg/day of amino acid early in the neonatal period while
      keeping the nitrogen to energy ratio above 1:100 and continuing with this protein
      intake during the infants stay in the hospital. At the present time long-term
      safety of this strategy is also not known. SUMMARY: Appropriately designed large
      scale randomized controlled trials are needed to determine the long-term safety
      and efficacy of early and aggressive administration of protein to very low birth
      weight infants.

PMID- 18332707
TI  - Pediatric glomerular diseases.

PMID- 18332708
TI  - Evaluation of hematuria and proteinuria: how should a pediatrician proceed?
AB  - PURPOSE OF REVIEW: Finding blood or protein in the urine of a patient can be the
      source of immense anxiety. The list of diseases that result in these findings is
      quite long. Thus, many pediatricians believe that an exhaustive investigation is
      necessary to be certain of the cause. The review will discuss the major causes of
      hematuria and proteinuria in the pediatric population, and discuss a rational
      approach to the evaluation of these conditions. RECENT FINDINGS: A number of
      recent studies have examined the results of mass screenings of school-age
      children and the final outcome of examination of children with hematuria and/or
      proteinuria. Most children with either isolated hematuria or isolated proteinuria
      had benign disease processes. Children with combined hematuria and proteinuria
      had a higher prevalence of significant kidney disease. SUMMARY: The urinalysis
      combined with the history and physical examination should indicate the cause of
      hematuria and proteinuria in most cases. Significant renal disease can be ruled
      out with a minimal amount of work-up in most patients. The presence of hematuria
      and proteinuria together significantly increases the likelihood of significant
      renal disease and should prompt a referral to a specialist.

PMID- 18332709
TI  - Evaluation and management of steroid-sensitive nephrotic syndrome.
AB  - PURPOSE OF REVIEW: This review examines new literature published in 2006 and 2007
      on steroid-sensitive nephrotic syndrome. RECENT FINDINGS: Steroid-sensitive
      nephrotic syndrome has long been thought to be due to lymphocyte-derived
      circulating factors leading to podocyte injury with subsequent proteinuria. New
      studies support this mechanism and implicate the T helper 2 cytokine IL-13. In
      addition a genetic mutation in familial nephrotic syndrome has been reported in a
      child, who responded to corticosteroid therapy. There are new clinical trial data
      supporting the efficacy of levamisole in steroid-sensitive nephrotic syndrome and
      preliminary trial data on mycophenolate mofetil supporting its efficacy as a
      steroid-sparing agent. Case reports support the use of the B cell-depleting
      antibody rituximab in steroid-sensitive nephrotic syndrome. Finally there is a
      meta-analysis of six studies suggesting an increase in the incidence of focal and
      segmental glomerulosclerosis in steroid-sensitive nephrotic syndrome over the
      last 20 years. SUMMARY: Progress has been made towards elucidating the cause of
      steroid-sensitive nephrotic syndrome. Data from adequately powered randomized
      controlled trials are still required to evaluate therapies for frequently
      relapsing and steroid-dependent steroid-sensitive nephrotic syndrome.

PMID- 18332710
TI  - Evaluation and management of steroid-unresponsive nephrotic syndrome.
AB  - PURPOSE OF REVIEW: Idiopathic nephrotic syndrome in children is commonly
      associated with minimal change disease and response to steroid therapy. Steroid
      unresponsive nephrotic syndrome is often characterized by persistent proteinuria
      and progression to chronic kidney disease. Focal segmental glomerulosclerosis is
      the leading cause of steroid-unresponsive nephrotic syndrome in childhood. There
      is no uniformed consensus as to the treatment of steroid-unresponsive nephrotic
      syndrome. Advances in the pathogenesis, genetics and biomarkers or surrogate
      markers may be useful for the diagnosis and identification of patients with
      steroid-unresponsive nephrotic syndrome, severity of disease, progression and
      response to therapy. RECENT FINDINGS: This review is intended to describe some of
      the recent changes in the epidemiology of steroid-unresponsive nephrotic
      syndrome, in particular focal segmental glomerulosclerosis, its pathogenesis and
      alternative therapies. SUMMARY: Recent studies in both children and adults have
      shown an increase in the incidence of focal segmental sclerosis as a cause of
      steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis and
      noninvasive methods of diagnosis may allow for the identification of steroid
      responsive patients.

PMID- 18332711
TI  - Acute poststreptococcal glomerulonephritis: an update.
AB  - PURPOSE OF REVIEW: Acute poststreptococcal glomerulonephritis, the most common
      form of acute glomerulonephritis in children, continues to be a major concern
      worldwide. This review summarizes the recent advances in the pathogenesis, host
      susceptibility factors, diverse clinical presentations, and treatment of the
      condition. RECENT FINDINGS: Several recent advances have been made in identifying
      streptococcal antigens that may play a pathogenic role in acute poststreptococcal
      glomerulonephritis. Nephritis-associated streptococcal plasmin receptor and
      streptococcal pyrogenic exotoxin B are currently considered major putative
      nephritogens. Host susceptibility factors including HLA-DRB1*03011 have been
      found at a higher frequency in acute poststreptococcal glomerulonephritis
      patients than in healthy controls. Reversible posterior leukoencephalopathy and
      autoimmune hemolytic anemia are newly reported clinical associations with the
      disease. Studies from developing countries question whether the outcome is always
      benign. Treatment remains mostly conservative; however, controversy exists over
      the use of aggressive therapy with poor prognostic factors. SUMMARY: Severe group
      A streptococcal disease including acute poststreptococcal glomerulonephritis
      remains a cause of morbidity and mortality in developing countries and among
      impoverished populations. Various reports on the diverse clinical manifestations
      that can be associated with the condition will aid physicians in prompt diagnosis
      and intervention, while studies focusing on better understanding of
      immunopathogenesis may facilitate vaccine development and prevention.

PMID- 18332712
TI  - IgA nephropathy and Henoch-Schonlein purpura nephritis.
AB  - PURPOSE OF REVIEW: IgA nephropathy and Henoch-Schonlein purpura nephritis are
      common glomerular disorders in pediatrics that can potentially progress to end
      stage renal disease in some patients. This review summarizes our current
      understanding of the pathogenesis of these closely related conditions and
      discusses the rationale for development of diagnostic tests and prognostic
      markers. The review also presents the best data for long-term outcome, clinical
      markers of prognosis, and the results of randomized controlled trials. RECENT
      FINDINGS: Our understanding of the defective galactosylation of O-linked glycans
      in the hinge region of human IgA1 and its role in the pathogenesis of IgA
      nephropathy and Henoch-Schonlein purpura nephritis has evolved over the past
      decade. This review discusses studies that suggest that demonstration of
      galactose-deficient IgA1 in the serum may become an important diagnostic tool for
      these conditions. Proteomic techniques for development of biomarkers for
      diagnosis and prognosis show promise. Although data from randomized controlled
      trials have failed to support the use of immunosuppressive agents in pediatric
      IgA nephropathy and Henoch-Schonlein purpura nephritis, recent data indicate that
      angiotensin converting enzyme inhibitor therapy is indicated for reduction of
      proteinuria. SUMMARY: Childhood IgA nephropathy and Henoch-Schonlein purpura
      nephritis have the potential for serious morbidity, either during childhood or
      later in adulthood. In the future clinical tests will be used for noninvasive
      diagnosis and as markers for judging response to treatment, particularly in those
      individuals at highest risk for eventual progression to end-stage renal disease.

PMID- 18332713
TI  - Therapeutics and toxicology.

PMID- 18332714
TI  - Very low lead exposures and children's neurodevelopment.
AB  - PURPOSE OF REVIEW: We remain far from achieving the goal of eliminating lead
      associated neurodevelopmental morbidities in children. New evidence regarding the
      blood lead levels at which morbidities occur have led to calls for the Centers
      for Disease Control and Prevention to reduce the current screening guideline of
      10 microg/dl. The review evaluates the basis for these calls. RECENT FINDINGS:
      Adverse outcomes, such as reduced intelligence quotient and academic deficits,
      occur at levels below 10 microg/dl. Some studies suggest that the rate of decline
      in performance is greater at levels below 10 microg/dl than above 10 microg/dl,
      although a plausible mechanism has not been identified. Increased exposure is
      also associated with neuropsychiatric disorders such as attention deficit
      hyperactivity disorder and antisocial behavior. Functional imaging studies are
      beginning to provide insight into the neural substrate of lead's
      neurodevelopmental effects. Current protocols for chelation therapy appear
      ineffective in preventing such effects, although environmental enrichment might
      do so. SUMMARY: No level of lead exposure appears to be 'safe' and even the
      current 'low' levels of exposure in children are associated with
      neurodevelopmental deficits. Primary prevention of exposure provides the best
      hope of mitigating the impact of this preventable disease.

PMID- 18332716
TI  - Prenatal tobacco smoke and postnatal secondhand smoke exposure and child
      neurodevelopment.
AB  - PURPOSE: To review the recent scientific literature examining the association of
      prenatal tobacco and postnatal secondhand smoke exposure and child
      neurodevelopment. RECENT FINDINGS: Low birth weight and decreased in-utero brain
      growth are two of multiple potential etiologic pathways proposed as mediating the
      effects of prenatal tobacco smoke exposure on child neurodevelopment. These
      negative effects of prenatal exposure have been consistently demonstrated in
      animal models, and in humans have been found as early as the newborn period. The
      literature on both prenatal and postnatal exposure is remarkably consistent in
      showing associations with increased rates of behavior problems, including
      irritability, oppositional defiant behavior, conduct disorders and attention
      deficit hyperactivity disorder. A more rudimentary literature also suggests
      deficits in intelligence quotient. Recent studies have focused on elucidating the
      complex interaction among tobacco exposure, genetics and environmental factors.
      Questions still remain about the relative roles of prenatal vs. postnatal
      exposure and the potential role of genetic and social confounders, limiting the
      ability to infer a causal nature to these associations at this time. The
      consistency of findings across studies is, however, highly suggestive of a causal
      relationship between environmental tobacco exposure and adverse behavioral and
      cognitive outcomes in children. SUMMARY: Prenatal tobacco and postnatal
      secondhand smoke exposure is consistently associated with problems in multiple
      domains of children's neurodevelopment and behavior.

PMID- 18332715
TI  - Fish consumption, methylmercury and child neurodevelopment.
AB  - PURPOSE OF REVIEW: To summarize recent evidence regarding associations of early
      life exposure to mercury from maternal fish consumption during pregnancy,
      thimerosal in vaccines and dental amalgam with child neurodevelopment. RECENT
      FINDINGS: Recent publications have built upon previous evidence demonstrating
      mild detrimental neurocognitive effects from prenatal methylmercury exposure from
      maternal fish consumption during pregnancy. New studies examining the effects of
      prenatal fish consumption as well as methylmercury suggest there are benefits
      from prenatal fish consumption, but also that consumption of fish high in mercury
      should be avoided. Future studies incorporating information on both the
      methylmercury and the docosahexaenoic acid contained within fish will help to
      refine recommendations to optimize outcomes for mothers and children. Additional
      recent studies have supported the safety of vaccines containing thimerosal and of
      dental amalgam for repair of dental caries in children. SUMMARY: Exposure to
      mercury may harm child development. Interventions intended to reduce exposure to
      low levels of mercury in early life must, however, be carefully evaluated in
      consideration of the potential attendant harm from resultant behavior changes,
      such as reduced docosahexaenoic acid exposure from lower seafood intake, reduced
      uptake of childhood vaccinations and suboptimal dental care.

PMID- 18332717
TI  - Pesticides and child neurodevelopment.
AB  - PURPOSE OF REVIEW: This review summarizes the recent research on pesticide
      exposure and child neurobehavioral development with a focus on in-utero exposure
      to organochlorine and organophosphate pesticides. RECENT FINDINGS: Recent studies
      on in-utero exposure to the organochlorine pesticide
      dichlorodiphenyltrichloroethane and its breakdown product,
      dichlorodiphenyldichloroethene, indicate that exposure is associated with poorer
      infant (6 months and older) and child neurodevelopment. Yet, the studies differ
      on the domain of development that is affected. Research on organophosphate
      pesticide exposure and neurodevelopment is limited but suggests some negative
      association of exposure and neurodevelopment at certain ages. Two reports agree
      that increased levels of organophosphate exposure in utero result in greater
      numbers of abnormal reflexes in neonates and studies in older infants and young
      children also point to a negative association with development. In young children
      (2-3 years) two separate studies observed an increase in maternally reported
      pervasive developmental disorder with increased levels of organophosphate
      exposure. SUMMARY: Given that the literature suggests a link between
      organochlorine and in-utero pesticide exposure and impaired child
      neurodevelopment, clinicians should educate parents about prevention of exposure,
      especially in populations living in agricultural areas or where household use is
      common.

PMID- 18332718
TI  - Polychlorinated biphenyls, organochlorine pesticides and neurodevelopment.
AB  - PURPOSE OF REVIEW: Although environmental levels of polychlorinated biphenyls and
      certain organochlorine pesticides--hexachlorobenzene, dichlorodiphenyl
      trichloroethane and its primary metabolite, dichlorodiphenyl dichloroethene--are
      generally on the decline, early-life exposures to these prevalent contaminants
      continue. The review will describe current understanding of the potential
      neurodevelopmental consequences of low-level exposures to these contaminants.
      RECENT FINDINGS: Animal models suggest that early-life exposures to
      polychlorinated biphenyls, dichlorodiphenyl trichloroethane/dichlorodiphenyl
      dichloroethene or hexachlorobenzene are associated with decreased cognitive or
      behavioral function in later development. Despite almost 30 years of research,
      however, results of human studies are inconsistent regarding the nature of the
      observed effects and their persistence over time. Overall, epidemiologic studies
      support modest associations of primarily prenatal polychlorinated biphenyl
      exposures with differences in neuromotor development, decrements in cognition and
      behavioral deficits, particularly regarding attention and impulse control. There
      are limited published human data regarding potential neurodevelopmental
      toxicities of early-life exposures to dichlorodiphenyl
      trichloroethane/dichlorodiphenyl dichloroethene and hexachlorobenzene. SUMMARY:
      Exposures to polychlorinated biphenyls, dichlorodiphenyl
      trichloroethane/dichlorodiphenyl dichloroethene and hexachlorobenzene are likely
      detrimental to neurodevelopment. Effective control of exposure is complicated by
      variable exposure sources and variable contaminant levels in food, particularly
      fish, for which it is important to balance the risk of contaminants with
      nutritional benefits.

PMID- 18332719
TI  - Update on child maltreatment.
AB  - PURPOSE OF REVIEW: The authors discuss the significance of studies published over
      the previous year regarding assessment and treatment and prevention of child
      maltreatment, including physical and sexual abuse, inflicted traumatic brain
      injury, and child neglect. RECENT FINDINGS: The evidence base for many forms of
      child abuse is growing. As clinicians begin to understand the factors which may
      increase child vulnerability to abuse, more sophisticated and focused prevention
      efforts are being implemented. In response to a very public reprimand by the
      General Medical Council of two child abuse pediatricians, which was felt by many
      to be unwarranted, the UK government re-emphasized its commitment to the
      protection of children. In the US, this well-publicized set of events has renewed
      the medical community's commitment to the recognition of child abuse pediatrics
      as a formal subspecialty. Several authors detail the short-term and long-term
      outcome of varying forms of abuse for children as they grow into adults,
      reinforcing the importance of community efforts to prevent abuse and support
      families during times of heightened stress such as the current war in Iraq.
      SUMMARY: The short-term and long-term impact of child maltreatment is significant
      not only for individuals, but for families and communities where abuse is taking
      place. General pediatricians have an important role to play with families and in
      the community as advocates for the protection of children.

PMID- 18332721
TI  - Bibliography. Current world literature. Neonatology and perinatology.

PMID- 18332720
TI  - Case report: consumptive hypothyroidism consequent to multiple infantile hepatic
      haemangiomas.
AB  - A 10-month-old infant with multiple infantile hepatic hemangiomas and
      developmental delay is reported. He was found to be profoundly hypothyroid.
      Evaluation and management issues are discussed. This case emphasizes the
      importance of screening for hypothyroidism in patients with hemangiomas and the
      potential therapeutic benefit of prednisolone therapy in this condition.

PMID- 18332722
TI  - Fluence-to-absorbed dose conversion coefficients for use in radiological
      protection of embryo and foetus against external exposure to electrons from 10
      MeV TO 10 GeV.
AB  - Electrons as primary and more often as secondary radiation exist commonly in the
      environment and workplaces. No conversion coefficients are yet available, in the
      literature, for use in radiological protection of embryo and foetus against
      external exposure to electrons. This study uses mathematical models developed by
      the Radiation Protection Bureau, Health Canada, for the embryo of 8 wk and for
      the foetus of 3, 6, and 9 mo. Monte Carlo code MCNPX is used to determine mean
      absorbed doses to the embryo and foetus when the mother is exposed to external
      electron fields. Monoenergetic electrons ranging from 10 MeV to 10 GeV were
      considered. The irradiation geometries include antero-posterior (AP), postero
      anterior (PA), lateral (LAT), rotational (ROT), isotropic (ISO), and top-down
      (TOP). At each of these irradiation geometries, absorbed doses to the foetal
      brain and body were calculated for the embryo of 8 wk and the foetus of 3, 6, and
      9 mo. Electron fluence-to-absorbed dose conversion coefficients were derived for
      the four prenatal ages.

PMID- 18332723
TI  - Evaluation of erythemal UV effective irradiance from UV lamp exposure and the
      application in shield metal arc welding processing.
AB  - Ultraviolet radiation (UVR) exposure is known to cause potential effects such as
      erythema in skin. For UV-induced erythema (sunburn), the action spectrum from the
      Commission Internationale de l'Eclairage, International Commission on
      Illumination (CIE) was adopted. Erythemal UV effects from UVR lamp exposure were
      investigated with commercial spectroradiometry devices in this research. Three
      kinds of portable UV germicidal lamps with broadband UVA (BB UVA, 350-400 nm),
      broadband UVB (BB UVB, 280-350 nm), and narrowband UVC (NB UVC, 254 nm)
      wavelengths served as the UVR emission sources. An action spectrum expresses the
      effectiveness of radiation for assessing the hazard of UVR in the erythemal
      action spectrum from 250-400 nm. The UV Index (UVI) is an irradiance scale
      computed by multiplying the CIE erythemal irradiance integral in milliwatts per
      square meter by 0.04 m mW. A comprehensive approach to detecting erythemal UVR
      magnitude was developed to monitor the effective exposure from UV lamps. The
      erythemal UVR measurement was established and the exposure assessment was applied
      to monitor erythemal UVR magnitude from shield metal arc welding (SMAW)
      processing. From this study, the erythemal UVR exposures were assessed and
      evaluated with environmental solar simulation of the UVI exposure.

PMID- 18332724
TI  - Spatial distribution of soil contamination by 137Cs and 239,240Pu in the village
      of Dolon near the Semipalatinsk nuclear test site: new information on traces of
      the radioactive plume from the 29 August 1949 nuclear test.
AB  - The village of Dolon located about 60 km northeast from the border of the
      Semipalatinsk Nuclear Test Site in Kazakhstan is one of the most affected
      inhabited settlements as a result of nuclear tests by the former USSR.
      Radioactive contamination in Dolon was mainly caused by the first USSR nuclear
      test on 29 August 1949. As part of the efforts to reconstruct the radiation dose
      in Dolon, Cs and Pu in soil samples collected from 26 locations in the vicinity
      of and within the village were measured to determine the width and position of
      the center-axis of the radioactive plume that passed over the village from the 29
      August 1949 nuclear test. Measured soil inventories of Cs and Pu were plotted as
      a function of the distance from the supposed center-axis of the plume. A clear
      shape similar to a Gaussian function was observed in their spatial distributions
      with each maximum around a center-axis. It was suggested that the plume width
      that contaminated Dolon was at most 10 km and the real center-axis of the
      radioactive plume passed 0.7-0.9 km north of the supposed centerline. A peak-like
      shape with the maximum near the center-axis was also observed in the spatial
      distribution of the Pu/Cs activity ratio, which may reflect the fractionation
      effect between Pu and Cs during the deposition process. These results support the
      recently reported results. The data obtained here will provide useful information
      on the efforts to estimate radiation dose in Dolon as reliably as possible.
      Health Phys. 94(4):328-337; 2008.

PMID- 18332725
TI  - Evaluation of a new mammographic film: methods and considerations.
AB  - In this study the performance of a new mammographic film, the XMA (Retina), was
      evaluated in comparison with HT (Agfa). The comparison was made in terms of
      sensitometric characteristics and in terms of image quality and speed when
      combined with four different cassettes-HDS (Agfa), Min-R 2000 and Min-R 2190
      (Kodak), and AD-MA (Fuji)-using the Leeds TOR(MAX) Mammographic Quality Control
      phantom. The entrance surface air kerma was calculated from exposure factors and
      the relative speed of each screen-film combination was determined. These tests
      revealed that XMA requires about 40% less dose than HT when combined with the
      same intensifying screen, at a penalty of less than 8% in image quality. When
      combined with AD-MA the XMA presents the greatest speed, whereas the Min-R 2190
      is the best compromise between image quality and breast dose. The above values
      are indicative of the dilemma that medical physicists and radiologists face when
      it comes to the selection of a screen-film combination for mammography. Both
      image quality and breast dose should be considered, but strict instructions on
      what weight should be assigned to each parameter have not been established yet.
      Health Phys. 94(4):338-344; 2008.

PMID- 18332726
TI  - Statistical multipath exposure of a human in a realistic electromagnetic
      environment.
AB  - A new and fast numerical method is presented to assess the whole-body averaged
      specific absorption rate (SAR) in a human body model in a realistic
      electromagnetic environment. The method requires a minimum set of initial
      numerical simulations with a 3D electromagnetic solver. From the initial
      simulation results, the absorption can be quickly (within 1 s) determined in a
      realistic electromagnetic environment. The realistic electromagnetic environment
      has been modeled as a finite sum of incident plane waves. The presented fast
      method serves as a substitute for brute-force 3D electromagnetic simulations.
      Therefore, the method must only be validated with brute-force 3D electromagnetic
      simulations in terms of whole-body averaged SAR, and excellent agreement has been
      observed. The method has been applied to assess the cumulative distribution
      function of the whole-body averaged SAR in a spheroid human body model for four
      types of realistic electromagnetic environments. We observed that for all the
      four environments the whole-body averaged SAR complies with the International
      Commission on Non Ionizing Radiation Protection basic restriction for general
      public. Furthermore, the whole-body averaged SAR for a realistic exposure exceeds
      the worst-case single plane wave exposure in approximately 10% of the exposure
      samples.

PMID- 18332727
TI  - The NORMAN phantom vs. the BOMAB phantom: are they different?
AB  - This paper describes the implementation of the NORMAN phantom with the Human
      Monitoring Laboratory's Monte Carlo simulator, the problems that were
      encountered, and their solution. The NORMAN phantom has been compared with the
      reference man BOMAB phantom in three different whole body counting geometries: a
      scanning detector system (WBC1), and two stand-up whole body counters (WBC2,
      WBC3) that have different reference points for their counting geometry. The
      average agreement (taken over all energies) of the two phantoms is approximately
      a factor of 1.15 on any given counting system. For the first two systems (WBC1,
      WBC2) the BOMAB has the highest counting efficiency, whereas it is reversed on
      the third system (WBC3). Considering the differences between the two phantoms,
      the agreement is good.

PMID- 18332728
TI  - Determining the sample size required for a community radon survey.
AB  - Radon measurements in homes and other buildings have been included in various
      community health surveys often dealing with only a few hundred randomly sampled
      households. It would be interesting to know whether such a small sample size can
      adequately represent the radon distribution in a large community. An analysis of
      radon measurement data obtained from the Winnipeg case-control study with
      randomly sampled subsets of different sizes has showed that a sample size of one
      to several hundred can serve the survey purpose well.

PMID- 18332729
TI  - Problems found using a radon stripping algorithm for retrospective assessment of
      air filter samples.
AB  - An evaluation of a large number of air sample filters was undertaken using a
      commercial alpha and beta spectroscopy system employing a passive implanted
      planar silicon (PIPS) detector. Samples were only measured after air flow through
      the filters had ceased. Use of a commercial radon stripping algorithm was
      implemented to discriminate anthropogenic alpha activity on the filters from the
      radon progeny. When uncontaminated air filters were evaluated, the results showed
      that there was a time-dependent bias in both average estimates and measurement
      dispersion of anthropogenic activity estimates with the relative bias being small
      compared to the dispersion, indicating that the system would not give false
      positive indications for an appropriately set decision level. By also measuring
      environmental air sample filters simultaneously with electroplated alpha sources,
      use of the radon stripping algorithm demonstrated a number of substantial
      unexpected deviations from calibrated values indicating that the system would
      give false negative indications. Use of the current algorithm is, therefore, not
      recommended for general assay applications. Use of the PIPS detector should only
      be utilized for gross counting without appropriate modifications to the curve
      fitting algorithm. As a screening method, the radon stripping algorithm might be
      expected to see elevated alpha activities from pure Pu on air sample filters (not
      due to radon progeny) around the 200 disintegrations per minute level.

PMID- 18332730
TI  - ICNIRP statement on EMF-emitting new technologies.

PMID- 18332734
TI  - Changing governmental regulations.

PMID- 18332735
TI  - Recruitment and retention of speech-language pathologists: putting home
      healthcare on the radar.
AB  - The problems that home health managers experience in hiring speech-language
      pathologists (SLPs) are not surprising. The surveys of the profession show that
      insufficient numbers of SLPs exist in the workforce to fill all the available
      positions. In competing with schools and other healthcare settings, home health
      recruiters also must overcome SLPs' lack of exposure to home health during their
      formative student experiences. This article provides some tips about where to
      find SLPs and how to excite them about home healthcare--and once having hired
      them, how to keep them.

PMID- 18332736
TI  - Adapting to a prospective payment system: a research study of visiting nurses.
AB  - Individual interviews were conducted with twelve visiting home care nurses in
      three home care agencies in a Midwest state to determine how they adapted to the
      Prospective Payment System (PPS) of 2000. Strategies used by the nurses included
      organization, understanding the documentation, financial awareness, greater
      emphasis on discharge planning, patient accountability, greater emphasis on
      teaching, and team work.

PMID- 18332737
TI  - Incorporating spirituality into home care at the end of life.
AB  - The home health clinician may be aware that the patient has spiritual needs, but
      may be unable to respond to these needs. This may be due to inadequate education
      or the assumption that spiritual needs should be addressed by chaplains, clergy,
      or other "spiritual" care providers. In reality, clinicians in the home are in
      the best position to offer spiritual support when caring for patients in their
      homes at the end of life.

PMID- 18332739
TI  - Impact of a care coordination and support strategic partnership on clinical
      outcomes.
AB  - A strategic partnership between a nursing care coordination telephone support
      program and a home healthcare agency was evaluated. The study was supported by
      the Centers for Medicare and Medicaid. According to the results, the partnership
      was a clinically effective service that proved satisfactory to family caregivers,
      improved the use of community services, and reduced inpatient use and costs
      without affecting mortality.

PMID- 18332740
TI  - Uninvited "guests" in patient homes.
AB  - This article reviews commonly prescribed medications used to treat insect bites
      or stings in a case study format. The review describes the implications of
      treatment for a patient with chronic kidney disease and acute hepatic obstruction
      who experienced an insect bite.

PMID- 18332742
TI  - 2008 refinements to the Medicare Home Health Prospective Payment System.
AB  - On January 1, 2008, Centers for Medicare and Medicaid Services (CMS) implemented
      refinements to the Prospective Payment System (PPS). This is the first change to
      the way CMS reimburses Medicare patients receiving home health services since the
      inception of PPS in 2000. The calculation for the exact episode payment has
      changed significantly, but from a clinical management perspective, the focus must
      be on ensuring that both the Outcome and Assessment Information Set (OASIS)
      assessment and the International Classification of Diseases (ICD)-9 CM coding are
      completed accurately-the same things all clinicians should be doing currently!
      This article will describe the structural, payment adjustment, and base rate
      changes for Medicare home care reimbursement that were implemented by CMS on
      January 1, 2008.

PMID- 18332743
TI  - The proper care and feeding of a surveyor.

PMID- 18332745
TI  - Life's little lessons leave big impact.

PMID- 18332746
TI  - My say: patients are still falling through the cracks in the healthcare maze, and
      proactive discharge planning can help.

PMID- 18332747
TI  - Guaranteeing treatment for everyone: the need for educational triage.

PMID- 18332752
TI  - Pulling out, extraction or avulsion?

PMID- 18332753
TI  - Implant success, survival, and failure: the International Congress of Oral
      Implantologists (ICOI) Pisa Consensus Conference.
AB  - The primary function of a dental implant is to act as an abutment for a
      prosthetic device, similar to a natural tooth root and crown. Any success
      criteria, therefore, must include first and foremost support of a functional
      prosthesis. In addition, although clinical criteria for prosthetic success are
      beyond the scope of this article, patient satisfaction with the esthetic
      appearance of the implant restoration is necessary in clinical practice. The
      restoring dentist designs and fabricates a prosthesis similar to one supported by
      a tooth, and as such often evaluates and treats the dental implant similarly to a
      natural tooth. Yet, fundamental differences in the support system between these
      entities should be recognized. The purpose of this article is to use a few
      indices developed for natural teeth as an index that is specific for endosteal
      root-form implants. This article is also intended to update and upgrade what is
      purported to be implant success, implant survival, and implant failure. The
      Health Scale presented in this article was developed and accepted by the
      International Congress of Oral Implantologists Consensus Conference for Implant
      Success in Pisa, Italy, October 2007.

PMID- 18332754
TI  - A two-stage full-arch ridge expansion technique: review of the literature and
      clinical guidelines.
AB  - Ridge expansion techniques have been acknowledged to offer several advantages in
      the correction of ridge deformities. The expanded defect heals in a similar
      manner to an extraction socket. In selected cases patients can wear their
      dentures after surgery. Secondary surgical sites are not a prerequisite, and
      simultaneous implant placement can be achieved during ridge expansion. The
      limitation of this technique lies in its inability to create bone vertically.
      Therefore, it is not indicated for the correction of vertical defects. The
      application of the split ridge expansion technique has been reported in the
      literature as it pertains to partially edentulous deficient ridges. The purpose
      of this article was to present the application of the split ridge expansion
      technique in the fully edentulous maxilla and discuss the distinction between the
      immediate or one-stage approach and the delayed or two-stage approach. Histologic
      results are discussed. Two case reports demonstrate the results that can be
      obtained with this technique.

PMID- 18332755
TI  - Maxillary sinus membrane repair: update on technique for large and complete
      perforations.
AB  - Maxillary sinus membrane perforation is the most common complication that occurs
      with sinus elevation augmentation surgery. A technique using a slow resorbing
      type I collagen membrane for repair of large and complete sinus membrane
      perforations is described. The biocompatibility and semirigid structural
      integrity of this membrane, along with external tack fixation, allows for optimal
      membrane stabilization and maintenance.

PMID- 18332756
TI  - Minor tooth movements using microimplant anchorage: case reports.
AB  - For the treatment of extruded or tipped molars, various conventional techniques
      have been used. But those methods may lead to undesirable movement of the
      anchorage units and lengthen treatment time because of limited tooth-borne
      anchorage potential. Introduction of microimplants as orthodontic anchorage has
      expanded treatment possibilities because of their advantages. Some advantages are
      a less complex surgical procedure, decrease in cost, immediate loading, and their
      ability to be placed in any area of the alveolar bone. This article will
      illustrate clinical experiences in patients who were treated with the intrusion
      of overerupted molars, the up-righting of tilted molars, and other clinical
      applications for minor tooth movements. Anchorage control was achieved with the
      surgical insertion of titanium microimplants for immediate loading in the
      alveolar bone. When needed, minimal fixed appliances were used and orthodontic
      treatment was completed without any other complications.

PMID- 18332757
TI  - Cortical tenting grafting technique in the severely atrophic alveolar ridge for
      implant site preparation.
AB  - OBJECTIVES: Alveolar ridge augmentation using intraoral autogenous block grafts
      to augment localized alveolar ridge defects before implant placement is a
      predictable method. However, large severely atrophic edentulous segments may
      require extraoral donor sites. The purpose of this study was to evaluate the
      effectiveness of using intraoral cortical block grafts in combination with
      particulate human mineralized allograft, in a "tenting" fashion, to augment large
      atrophic alveolar ridge defects for implant placement. MATERIALS: This
      prospective case study evaluated augmentation in 10 consecutive patients with
      severely resorbed alveolar ridges missing a minimum of 4 adjacent teeth. Before
      augmentation, all grafted sites were deemed inadequate for placement of a
      standard 4-mm-diameter implant. Horizontal ridge augmentation was performed using
      autologous membranous cortical bone grafts from an oral donor site to tent out
      the soft tissue matrix and periosteum for the adjacent particulate allograft. The
      ridges were clinically evaluated 4 to 5 months after augmentation, and 42
      implants were placed at that time. RESULTS: Implants were successfully placed at
      all grafted sites 4 to 5 months after the original graft date. Clinical
      evaluation of the grafted sites upon re-entry revealed uniform ridge anatomy. All
      edentulous segments had at least 2 implants placed of at least 4.0 mm diameter.
      In all, 42 implants were placed into grafted sites in the 10 patients. Implants
      were checked for osseointegration by using a counter torque of 35 N.cm. One
      implant failed to integrate. Mean follow-up was 22 months after implant
      placement. All augmented ridges had retained their functional and esthetic
      integrity at 1 year after original augmentation. CONCLUSION: Tenting of the
      periosteum and soft tissue matrix using a cortical bone block maintains space and
      minimizes resorption of the particulate allograft volume. In addition, bridging
      the cortical blocks with particulate bone avoids unaesthetic ridge defects
      between cortical block grafts in larger ridge defects. The result was a more
      uniform and esthetic alveolar ridge, capable of maintaining an implant-supported
      prosthesis. The technique offers predictable functional and esthetic
      reconstruction of large-volume defects without extensive amounts of autogenous
      bone. This offers a superior functional and esthetic result than with either
      cortical or particulate grafting alone.

PMID- 18332758
TI  - A new transitional abutment for immediate aesthetics and function.
AB  - Maintenance of the patient's self-esteem and confidence throughout the implant
      treatment process is essential. Development of a provisional prosthesis that will
      be stable and esthetic should begin with the initial examination and should
      involve all members of the implant team. This article presents 3 cases that
      demonstrate a team-centered approach in using a poly (acrylether) ketone plastic
      provisional abutment (Peek). This abutment, cost-effective and easily modified,
      supports a transitional prosthesis that is delivered at the time of implant
      placement.

PMID- 18332759
TI  - Immediate loading of the grafted maxillary sinus using platelet rich plasma and
      autogenous bone: a preliminary study with histologic and histomorphometric
      analysis.
AB  - OBJECTIVE: The goal of this clinical study was to evaluate dental implant
      survival rates using the concept of a nonfunctional, immediate loading protocol
      with nonsplinted dental implants in the grafted maxillary sinus during a 52-week
      period. Random histomorphological and histomorphometric analysis was completed to
      evaluate the early healing effect of platelet rich plasma (PRP) and 50%
      autogenous bone combined with 3 different substitute graft materials. MATERIALS:
      Four to 8 months after grafting the sinus with PRP sprayed autogenous bone
      combined with 3 different substitute graft materials in a 50:50 composite ratio,
      27 hydroxyapatite- coated dental implants were surgically placed in 41 patients
      and immediately loaded between 48 hours and 5 days later with custom titanium
      abutments and acrylic provisional restorations placed out of functional
      occlusion. Six months later, definitive ceramometal restorations were cemented on
      to the custom abutments. RESULTS: During a 52-week observation period, no
      implants were lost. Between 4 and 8 months of graft healing time, histologic and
      histomorphometric analysis revealed formation of new vital bone in different
      graft specimens ranging from 77% to 100%. CONCLUSION: The preliminary results of
      this clinical study indicate that immediate nonfunctional loading using PRP and
      50% autogenous bone combined with different substitute graft materials is a
      predictable protocol in the grafted maxillary sinus as early as 4 months of
      postgrafting. The high implant survival rate is due to the early formation of
      large percentages of new vital bone as confirmed by using histologic and
      histomorphometric analysis.

PMID- 18332760
TI  - A clinical comparison of prosthetic complications of implant-supported
      overdentures with different attachment systems.
AB  - OBJECTIVES: The objective of this clinical study was to evaluate the prosthetic
      complications of patients with 2 to 4 implants splinted with a round bar or with
      2 to 4 unsplinted implants with ball attachments during the follow-up period.
      METHODS: A total of 26 patients were included in this study. Patients were
      randomly provided with a round bar or with ball attachments that were used to
      retain overdentures. During follow-up visits, the following prosthetic
      complications were recorded: round bar fracture, fractured overdenture, hygiene
      complications, abutment screw loose, worn O-ring or replacement of O-ring
      attachment, and fractured retention clip. The functioning period of overdentures
      in the round bar group ranged from 12 to 72 months (mean 49), and from 12 to 40
      months (mean 23) in the ball attachment group. RESULTS: A total of 20 prosthetic
      complications were recorded in both groups. No differences in prosthetic
      complications were observed for 2 attachment systems. CONCLUSION: Implant
      supported overdentures with bar or ball attachments may be considered to be
      reliable methods in the treatment of the edentulous individuals.

PMID- 18332761
TI  - Injectable bone applied for ridge augmentation and dental implant placement:
      human progress study.
AB  - PURPOSE: The aim of this study was to clinically evaluate the success of implants
      placed in conjunction with a new material, tissue-engineered bone, and the
      stability of the regenerated bone after functional loading on a long-term basis.
      METHODS: The tissue-engineered bone was applied to 14 cases, in which 6 patients
      were with partially or totally edentulous arches scheduled for sinus floor
      grafting and 8 patients underwent concurrent onlay plasty. RESULTS: This study
      showed that the injectable bone formation induced bone in this anatomical site in
      100% of the patients. The results also indicate that it might be possible to
      achieve the osseointegration of simultaneous implant placements with the grafts.
      CONCLUSIONS: It may be possible that injectable bone can shorten the period of
      implant treatment and reduce the patient's burden and expect good long-term
      prognosis.

PMID- 18332762
TI  - Surface characterization of three titanium dental implants.
AB  - PURPOSE: The aim of this study was to evaluate topographically and
      compositionally the rough surface of 3 different commercial titanium dental
      implants. MATERIALS: Bio Com Standard, Osseotite Implant, and Fixture MT
      Osseospeed were analyzed using scanning electron microscopy, atomic force
      microscopy, and energy dispersive spectroscopy. RESULTS: The scanning electron
      microscopy and atomic force microscopy analyses showed that the rough surface of
      Bio Com Standard presents numerous impressions superimposed by sharp pits, of
      Osseotite Implant many discrete sharp pits, and of Fixture MT Osseospeed a mixed
      feature appearance. The energy dispersive spectroscopy analysis of the rough
      implant surfaces revealed a small trace of Si found on the surface of Osseotite
      Implant. Fixture MT Osseospeed showed a nonhomogeneous distribution of the
      detected elements. CONCLUSION: The examined implants had a different rough
      surface topography, which was directly dependent on the type of treatment used.
      The differences concerning the surface morphology were leading in a
      characteristic nanotopography, which might influence the biologic activities at
      the implant-tissue interface. Surface oxygen concentrations also indicated
      differences in the oxide layer width between the examined implants, being minimal
      in Osseotite Implant and maximal in Fixture MT Osseospeed.

PMID- 18332763
TI  - Peptide-15 changes miRNA expression in osteoblast-like cells.
AB  - PURPOSE: Peptide-15 (P-15) is an analog of the cell-binding domain of collagen. P
      15 has been shown to facilitate physiological process in a way similar to
      collagen, to serve as anchorage for cells, and to promote the binding, migration,
      and differentiation of cells. However, how P-15 alters osteoblast activity to
      promote bone formation is poorly understood. We therefore attempted to address
      this question by using microarray techniques to investigate the microRNA (miRNA)
      expression in osteoblasts exposed to P-15. MATERIALS: The miRNA oligonucleotide
      microarray provides a novel method to carry out genome-wide miRNA profiling in
      human samples. By using miRNA microarrays containing 329 probe designed from
      human miRNA sequence, we identified in osteoblast-like cells line (MG-63) cul
      tured with P-15 several miRNA whose expression is significantly modified.
      RESULTS: We identified 11 up-regulated miRNA (i.e., mir-337, mir-15b, mir-377,
      mir-100, mir-148a, mir-125a, mir-199a, mir-221, mir-let-7d, mir-92, mir-23b) and
      six down-regulated miRNA (i.e., mir-422a, mir-19a, mir-224, mir-145, mir-22, mir
      29a). CONCLUSION: The data reported are, to our knowledge, the first on
      translation regulation in osteoblasts exposed to P-15. They can be relevant to
      better understand the molecular mechanism of bone regeneration and can serve as a
      model for comparing other materials with similar clinical effects.

PMID- 18332764
TI  - Success rate of immediate nonfunctional loaded single-tooth implants: immediate
      versus delayed implantation.
AB  - PURPOSE: The aim of this study was to evaluate the success rate of maxillary
      immediate nonfunctional single-tooth loaded implants used into fresh extraction
      sites (immediate placement condition) or healed ridge (delayed placement
      condition). MATERIALS AND METHODS: Eighty-two dental implants were placed in the
      maxilla of 64 consecutive patients from private practice office and from a
      specialization course in Implantology. Forty-six implants were inserted under
      immediate placement condition, and 36 were inserted under delayed placement
      condition. The criteria used to evaluate success rate were those previously
      described by Albrektsson and Zarb (Int J Prosthodont. 1993;6:95-105), and follow
      up period ranged from 18.0 to 39.7 months. RESULTS: Seventy-nine implants
      fulfilled the success rate criteria (96.3%). Moreover, differences concerning
      implantation condition were not significant (P = 0.33, Qui-square test): three of
      the failed implants were from immediate placement group (success rate of 93.5%),
      and none was from delayed placement group (success rate of 100.0%). CONCLUSION:
      In the present sample, no statistically significant differences were detected for
      immediate nonfunctional single-tooth loaded implants under immediate placement
      condition in comparison with those inserted under delayed placement condition;
      both protocols had high success rate in maxillary incisors, canines, and
      premolars areas.

PMID- 18332765
TI  - Electrical field effect on peri-implant osteogenesis: a histologic and
      histomorphometric study.
AB  - PURPOSE: Tissue response to injury, as occurs during wound healing, is a well
      organized biologic event. Both clinical and experimental studies have shown
      external electrical stimulation to enhance tissue repair. The effect of in situ
      electrical stimulation has been studied in experimental models of fracture
      healing, ostectomy, osteogenic distraction, and implants. The aim of the present
      study was to evaluate the effect of an electrical field on peri-implant wound
      healing, using an experimental model that involved placing a metallic laminar
      implant in rat tibia. MATERIALS: Forty male Wistar rats weighing approximately
      100 g were used. A titanium laminar implant (6 x 1 x 0.1 mm3) (Implant Vel,
      Buenos Aires, Argentina) was inserted through the hole and placed in the
      medullary compartment. The tissues were then repositioned and sutured carefully.
      An electric field generator (ECCEL, DAM, Argentina) was used to deliver the
      electric stimulus. The electric field plate was placed on the skin of both hind
      limbs. In sham group, the animals were subjected to the same procedure without
      connecting the plate to the electric field generator. All the animals were killed
      by ether overdose at 15 days of postimplantation. The tibiae were resected, fixed
      in 20% formalin, radiographed, and processed for embedding in methyl
      methacrylate. The ground sections were stained with 1% toluidine blue. The
      following parameters were evaluated: peri-implant bone volume and percentage of
      osseointegration. Statistical analysis of the results was performed using ANOVA
      (P < 0.05). RESULTS: Application of external positive or negative electrical
      fields using the experimental model (post-titanium implant bone healing in rat
      tibia), under the conditions stated herein, was found to enhance peri-implant
      lamellar bone volume compared with sham-treated animals. CONCLUSION: The use of a
      device generating a positive/negative electrical field resulted in the presence
      of woven bone.

PMID- 18332766
TI  - Association of HIV and malaria with mother-to-child transmission, birth outcomes,
      and child mortality.
AB  - OBJECTIVE: To assess the impact of HIV and malaria coinfection on mother-to-child
      HIV transmission (MTCT) and adverse birth outcomes. METHODS: One hundred nine HIV
      positive mother-infant pairs with a malaria diagnosis were identified in a
      community cohort and followed up postpartum. Maternal malaria was diagnosed by a
      rapid immunochromatographic test (ICT) on sera and histopathologic examination of
      placenta. Infant HIV was diagnosed within 6 weeks of birth using polymerase chain
      reaction (PCR) to capture in-utero and intrapartum HIV transmission. Log binomial
      models were used to assess the relative risk of MTCT, low birth weight, and
      preterm birth associated with malaria. RESULTS: Approximately 17.4% of infants
      were HIV positive at or around birth, and the prevalence of serologic and
      placental malaria were 31% and 32%, respectively. HIV-positive mothers with
      serological ICT malaria were significantly more likely to have low-birth-weight
      infants, and low-birth-weight infants had significantly higher risk of MTCT
      compared with infants of normal birth weight. Although placental and serologic
      ICT malaria were significantly associated with MTCT, after adjusting for maternal
      HIV viral load, the risk of MTCT was significantly increased only for mothers
      coinfected with placental malaria (relative risk [RR] = 7.9, P = 0.025).
      CONCLUSIONS: Placental malaria increases the risk of MTCT after adjustment for
      viral load. Programs should focus on enhanced malaria prevention during pregnancy
      to decrease the risk of adverse birth outcomes and MTCT.

PMID- 18332767
TI  - Disclosure of HIV status: the role of ethnicity among people living with HIV in
      London.
AB  - OBJECTIVE: To examine HIV disclosure among people living with HIV in London.
      METHODS: Between June 2004 and June 2005, 1687 people living with HIV (73%
      response) receiving medical care in National Health Service (NHS) clinics in
      northeast London completed a confidential, self-administered questionnaire.
      Respondents were asked whether they had told anyone else that they had HIV, and
      if so, whom. RESULTS: The analysis included 1407 people: 667 black African
      heterosexual respondents (453 women, 214 men) and 740 gay men (633 white, 107
      ethnic minority). The majority of respondents (88.0%) had told at least 1 other
      person about their HIV infection, but this varied between groups: white gay men,
      95.0%; ethnic minority gay men, 93.5%; black African heterosexual women, 84.8%;
      black African heterosexual men, 76.6% (P < 0.001). Black African heterosexual men
      (65.3%) and women (60.4%) were less likely to have told their current partner
      about their HIV infection than white (86.2%) or ethnic minority gay men (85.2%):
      black African men, adjusted odds ratio (AOR) 0.25, 95% confidence interval (CI)
      0.14, 0.44, P < 0.001; black African women, AOR 0.24, 95% CI 0.15, 0.39, P <
      0.001 (reference group, white gay men). Only 1 in 5 respondents (21.6%) had
      disclosed their HIV status to their employer (white gay men, 30.5%; ethnic
      minority gay men, 15.8%; black African heterosexual women, 10.5%; black African
      heterosexual men, 8.8%; P < 0.001). CONCLUSIONS: In this London study there were
      striking differences, by ethnicity, in the extent to which people with HIV
      disclosed their infection. This has important implications in light of the 2005
      Disability Discrimination Act and recent prosecutions in the UK for the reckless
      transmission of HIV.

PMID- 18332768
TI  - Monitoring of HIV-1 resistance in Tunisia (North Africa) with a dried plasma spot
      strategy.

PMID- 18332769
TI  - Risk factors for failure to be offered routine HIV testing among adult medical
      inpatients in Botswana.

PMID- 18332770
TI  - Saquinavir plus lopinavir/ritonavir versus amprenavir plus lopinavir/ritonavir
      for treating highly resistant patients in Brazil.

PMID- 18332773
TI  - A de-gloving injury in a Hispanic pressman.

PMID- 18332774
TI  - High gasoline prices and mortality from motor vehicle crashes and air pollution.
AB  - OBJECTIVE: To estimate the effects of increasing gas prices on mortality. METHOD:
      We developed a simulation-based partial equilibrium model that estimated the
      public health effects of a 20% rise in gas prices. Estimates on price elasticity
      for gasoline, price elasticity of motor vehicle crashes, relations among gasoline
      use, air pollution, and mortality were drawn from literature in economics,
      epidemiology, and medicine. RESULTS: For sustained 20% increases in gasoline
      prices over 1 year, and assuming other prices and factors were constant, we
      estimated: 1994 (range, 997 to 4984) fewer deaths from vehicle crashes and 600
      (range, 300 to 1500) fewer deaths from air pollution. Combining both, we
      estimated 2594 fewer deaths. A Monte Carlo simulation involving varying
      assumptions on elasticities and relations indicated that 95% of the combined
      reduction in deaths was between 1747 and 3714. CONCLUSION: Results suggest that
      high gas prices have public health implications.

PMID- 18332775
TI  - A randomized controlled trial of chair interventions on back and hip pain among
      sewing machine operators: the los angeles garment study.
AB  - OBJECTIVE: Determine whether an adjustable chair with a curved or a flat seat pan
      improved monthly back and hip pain scores in sewing machine operators. METHODS:
      This 4-month intervention study randomized 293 sewing machine operators with back
      and hip pain. The participants in the control group received a placebo
      intervention, and participants in the intervention groups received the placebo
      intervention and one of the two intervention chairs. RESULTS: Compared with the
      control group, mean pain improvement for the flat chair intervention was 0.43
      points (95% CI = 0.34, 0.51) per month, and mean pain improvement for the curved
      chair intervention was 0.25 points (95% CI = 0.16, 0.34) per month. CONCLUSIONS:
      A height-adjustable task chair with a swivel function can reduce back and hip
      pain in sewing machine operators. The findings may be relevant to workers who
      perform visual- and hand-intensive manufacturing jobs.

PMID- 18332776
TI  - How a health and safety management training program may improve the working
      environment in small- and medium-sized companies.
AB  - OBJECTIVE: The objective of this controlled intervention study was to investigate
      the effects of a 2-year training program in health and safety (H&S) management
      for managers at small- and medium-sized companies. METHODS: A total of 113
      managers of motor vehicle repair garages participated in the training and another
      113 garage managers served as a comparison group. The effects were measured using
      questionnaires sent before and after the intervention to the managers and blue
      collar workers at the garages. RESULTS: The intervention group managers reported
      significantly greater improvement of their H&S management system than the
      managers in the comparison group. The results also indicate that the management
      training positively affected how the workers regarded their supportive working
      environment. CONCLUSION: H&S management training may positively affect measures
      at both garage and individual levels.

PMID- 18332777
TI  - Promoting weight loss and blood pressure control at work: impact of an education
      and intervention program.
AB  - OBJECTIVE: To assess the impact of tailored intervention on body mass index (BMI)
      and blood pressure (BP) among hypertensive employees participating in an employer
      based BP screening program. METHODS: The quasi-experimental design involved
      screening subjects (n = 15,583) within the Merrill Lynch organization. A control
      group had BP and weight measurements plus education whereas experimental sites
      additionally received a pedometer, to measure physical activity, body fat
      measurement, and education encouraging physical activity. Change in BMI and BP
      were compared after 1 year. RESULTS: The experimental group (n = 47) demonstrated
      statistically significant improvements in BMI (P < 0.01) and systolic BP (P =
      0.04) versus control group (n = 94). Furthermore, 38.3% of the experimental group
      reported undertaking vigorous physical activity (>or=3x/wk) at 1-year; a 100%
      increase compared with baseline. CONCLUSIONS: A targeted worksite intervention
      program may be an effective way to lower BP and promote exercise and weight loss.

PMID- 18332778
TI  - Methodology to update the practice recommendations in the American College of
      Occupational and Environmental Medicine's Occupational Medicine Practice
      Guidelines, second edition.
AB  - OBJECTIVE: To ensure that revisions to the second edition of the American College
      of Occupational and Environmental Medicine (ACOEM) guidelines are as valid and
      useful as possible. METHODS: The ACOEM Guideline Methodology Committee searched
      and synthesized the evidence-based medicine literature on systematic review and
      guideline development. The resulting process and tools were tested during
      guideline revision, and changes were made to the tools and process. RESULTS: The
      methodology specifies problem formulation, literature search methods, screening
      of studies, quality rating, summarization of the body of literature,
      recommendation drafting and rating, "first principles" of medical logic and
      ethics, training, expert panel review, stakeholder input, external review, pilot
      testing and Board of Directors approval. CONCLUSIONS: The process and tools
      developed are consistent with international guideline assessment criteria,
      robust, and internally and externally valid.

PMID- 18332779
TI  - Return to work and degree of recovery among injured workers in California's
      Workers' Compensation system.
AB  - OBJECTIVES: To determine factors associated with return to work and self-reported
      degree of recovery among injured workers in California. METHODS: Using logistic
      regression and survey data from a representative sample of 965 workers injured
      between April 1 and June 30, 2005, we investigated the impact of the primary
      treating physician's (PTP) occupational medicine orientation and interpersonal
      behavior and access to and timeliness of care on return to work and degree of
      recovery, controlling for worker and injury characteristics. RESULTS: Some PTP
      behaviors significantly increased the likelihood of return to work and some
      degree of recovery, while recommendations for specialty care reduced the
      likelihood of returning to work or experiencing some degree of recovery.
      CONCLUSIONS: Targeting PTP behaviors and improving management of those referred
      for specialty care may improve return to work and degree of recovery of injured
      workers.

PMID- 18332780
TI  - Maternal occupation and risk for low birth weight delivery: assessment using
      state birth registry data.
AB  - OBJECTIVE: To determine the effects of employment on low birth weight (LBW) in a
      service-based economy, we evaluated the association of LBW delivery with
      occupational data collected in a state birth registry. METHODS: Occupational data
      in the 2000 Connecticut birth registry were coded for 41,009 singleton births.
      Associations between employment and LBW delivery were analyzed using logistic
      regression controlling for covariates in the registry data set. RESULTS: Evidence
      for improved LBW outcomes in working mothers did not persist when adjusted for
      maternal covariates. Among working mothers, elevated risk of LBW was seen in
      textile, food service, personal appearance, material dispatching or distributing,
      and retail sales workers. CONCLUSIONS: Improved overall birth outcomes seen in
      working mothers may arise from favorable demographic and health attributes.
      Higher LBW risk was seen in several types of service sector jobs and in textile
      work.

PMID- 18332781
TI  - Comparing the job strain and job demand-control-support models in direct-care
      disability workers: support for support.
AB  - OBJECTIVE: This study attempted to determine the relationship of physiological
      indices of stress (ie, cortisol and salivary immunoglobulin A) to the job strain
      and the job demand-control-support models. METHODS: A sample of 98 direct-care
      disability workers completed the Maslach Burnout Inventory and the Job Content
      Questionnaire. In addition, participants' morning saliva samples were analyzed
      for cortisol and salivary immunoglobulin A concentration levels. RESULTS: The job
      strain and job demand-control-support models were tested using structural
      equation modeling. The job demand-control-support model successfully fitted with
      the data and was able to predict physiological outcomes, the job strain model did
      not. The salivary immunoglobulin A scores, in comparison to the cortisol data,
      were predicted more successfully by these models. CONCLUSIONS: Researchers are
      encouraged to study if different employee groups are at-risk for differing types
      of stress-related-illness, which may be triggered by occupation-specific
      stressors and/or physiological reactions.

PMID- 18332782
TI  - Consensus criteria for screening commercial drivers for obstructive sleep apnea:
      evidence of efficacy.
AB  - OBJECTIVE: To validate the recently published consensus criteria for screening
      commercial drivers for obstructive sleep apnea (OSA). METHODS: A large,
      consecutive case series of commercial drivers was screened for OSA at a single
      occupational medicine clinic and those screening positive were referred for
      overnight polysomnography. RESULTS: One hundred ninety (13%) of 1443 individuals
      having commercial motor vehicle driver examinations screened positive for OSA.
      None of these would have been detected if the only screening were the questions
      on the current Commercial Driver Medical examination form. One hundred thirty
      four underwent polysomnography, and of those 94.8% had OSA, which is the best
      estimate of the positive predictive value of these consensus criteria in a
      population of truck drivers. CONCLUSION: The proposed screening criteria have a
      high positive predictive value in this population. This study lends support for
      the requirement to screen for OSA in commercial drivers.

PMID- 18332783
TI  - Diabetes and cancer in veterans of Operation Ranch Hand after adjustment for
      calendar period, days of spraying, and time spent in Southeast Asia.
AB  - BACKGROUND: The Air Force Health Study was launched in 1980 as part of a Federal
      effort to resolve the Agent Orange issue. OBJECTIVES: To study diabetes and
      cancer with additional adjustment for days of spraying, calendar period of
      service, and time spent in Southeast Asia (SEA). METHODS: This was a longitudinal
      study of veterans of Operation Ranch Hand, the unit responsible for spraying
      Agent Orange and other 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated
      herbicides in Vietnam from 1962 to 1971. RESULTS: Associations between TCDD and
      diabetes and between TCDD and cancer in Ranch Hand veterans are strengthened
      after adjustment for calendar period of service, days of spraying, and, for
      cancer, time spent in SEA. CONCLUSIONS: Calendar period of service, days of
      spraying, and time spent in SEA are important confounders in the Air Force Health
      Study.

PMID- 18332785
TI  - Ethnic disparities in traumatic occupational injury.
AB  - OBJECTIVE: Workers of different ethnicities differ in patterns of employment and
      occupational risks. We use the Illinois Trauma Registry to evaluate ethnic
      disparities among the occupational traumatic injuries occurring in the State of
      Illinois between 1997 and 2003. METHODS: We analyze incidence, severity, cause
      and place of injury, disability and in-hospital mortality. RESULTS: The incidence
      rates of traumatic injuries among Hispanics were more than two times higher than
      whites, however, the risk of severe injury (Injury Severity Score >or=16) was
      more than 50% lower. Among African-American workers, the incidence and severity
      of traumatic injuries were lower than whites. Machinery was the primary external
      cause of injury among Hispanics. blacks were disproportionately injured in road
      accidents and homicides/assaults. CONCLUSION: There are substantial racial/ethnic
      differences in incidence, severity and outcome of work-related traumatic injuries
      treated in level I and II trauma centers in Illinois.

PMID- 18332784
TI  - Is there an association between lifetime cumulative exposure and acute pulmonary
      responses to ozone?
AB  - OBJECTIVE: To investigate the potential effects of lifetime cumulative ozone (O3)
      exposure on acute pulmonary responses to O3. METHODS: Fifteen healthy subjects
      from a larger cohort of young adults were exposed to 200 ppb O3 for 4 hours
      followed by bronchoscopy and bronchoalveolar lavage 18 hours later. Lung
      function, symptom questionnaires, and blood samples were obtained before and
      after each exposure. Subjects' lifetime cumulative O3 exposures were estimated
      from residential histories and air-quality monitoring data. RESULTS: Acute
      exposure to O3 caused decrements in forced expiratory volume in 1 second (FEV1),
      maximal mid-expiratory flow rate (FEF25-75), and forced expiratory flow rate at
      75% of forced vital capacity (FEF75), and an increase in plasma clara cell
      protein (CC16) level. Changes in CC16 and lower respiratory symptoms, but not in
      lung function, were positively correlated with lifetime cumulative O3 exposure.
      CONCLUSION: Higher lifetime cumulative O3 exposure was associated with airway
      injury and respiratory symptom responses, but not with airway inflammatory or
      lung function responses, to acute O3 exposure.

PMID- 18332786
TI  - Impact of a hypertension management/health promotion program on commercial
      driver's license employees of a self-insured utility company.
AB  - OBJECTIVE: Federal regulations governing transportation safety disqualify
      commercial drivers with persistent uncontrolled hypertension. We sought to
      determine whether a hypertension management and health promotion program designed
      for commercial drivers improved blood pressure (BP) outcomes among drivers
      employed by a self-insured utility company. METHODS: This retrospective study
      examined the employment-related medical examinations of 501 randomly selected
      commercial drivers for measurements of BP, height, and weight taken before and
      after the intervention. RESULTS: After the program, significantly fewer employees
      had uncontrolled hypertension according to the Department of Transportation
      hypertension guidelines (17.2% vs 26.1%, P < 0.01). This improvement was
      consistent across subgroups defined by diabetes, obesity, and use of
      antihypertensive medication. CONCLUSIONS: An education program improved control
      of BP among commercial drivers, improving their health and safety, and reducing
      the number at high risk of medical disqualification.

PMID- 18332787
TI  - Burden of smoking and occupational exposure on etiology of chronic obstructive
      pulmonary disease in workers of Southern Italy.
AB  - OBJECTIVE: This study evaluates the burden of smoking and occupational exposure
      on chronic obstructive pulmonary disease (COPD). METHODS: Two thousand nineteen
      workers underwent a diagnostic protocol for COPD at the baseline and after 5 and
      10 years. Taking into account individual and occupational exposures the sample
      was divided in four groups. Prevalence, incidence of COPD, differences among
      groups, and logistic regression were calculated. RESULTS: Higher COPD prevalence
      and incidence were observed in the group with combined exposures. Smoking habits
      and occupational exposure were confirmed as risk factors for COPD and an
      interaction between smoking and occupational exposure was found. CONCLUSIONS:
      Workers exposed to both risk factors have to be considered in COPD high-risk
      class. Smoking cessation programs could play an important role particularly in
      activities where effects of smoking have a positive interaction with occupational
      exposure.

PMID- 18332788
TI  - Occupational medicine forum.

PMID- 18332791
TI  - Industrial nail gun injury to the anterior skull base: a case report and review
      of the literature.

PMID- 18332792
TI  - Delayed tracheal stenosis in an inhalation burn patient.

PMID- 18332793
TI  - A novel splinting technique to protect free flaps in major limb trauma.

PMID- 18332794
TI  - Operative repair or endovascular stent graft in blunt traumatic thoracic aortic
      injuries: results of an American Association for the Surgery of Trauma
      Multicenter Study.
AB  - INTRODUCTION: The purpose of this American Association for the Surgery of Trauma
      multicenter study is to assess the early efficacy and safety of endovascular
      stent grafts (SGs) in traumatic thoracic aortic injuries and compare outcomes
      with the standard operative repair (OR). PATIENTS: Prospective, multicenter
      study. Data for the following were collected: age, blood pressure, and Glasgow
      Coma Scale (GCS) at admission, type of aortic injury, injury severity score,
      abbreviate injury scale (AIS), transfusions, survival, ventilator days,
      complications, and intensive care unit and hospital days. The outcomes between
      the two groups (open repair or SG) were compared, adjusting for presence of
      critical extrathoracic trauma (head, abdomen, or extremity AIS >3), GCS score
      </=8, systolic blood pressure <90 mm Hg, and age >55 years. Separate
      multivariable analysis was performed, one for patients without and one for
      patients with associated critical extrathoracic injuries (head, abdomen, or
      extremity AIS >3), to compare the outcomes of the two therapeutic modalities
      adjusting for hypotension, GCS score </=8, and age >55 years. RESULTS: One
      hundred ninety-three patients met the criteria for inclusion. Overall, 125
      patients (64.9%) were selected for SG and 68 (35.2%) for OR. SG was selected in
      71.6% of the 74 patients with major extrathoracic injuries and in 60.0% of the
      115 patients with no major extrathoracic injuries. SG patients were significantly
      older than OR patients. Overall, 25 patients in the SG group (20.0%) developed 32
      device-related complications. There were 18 endoleaks (14.4%), 6 of which needed
      open repair. Procedure-related paraplegia developed in 2.9% in the OR and 0.8% in
      the SG groups (p = 0.28). Multivariable analysis adjusting for severe
      extrathoracic injuries, hypotension, GCS, and age, showed that the SG group had a
      significantly lower mortality (adjusted odds ratio: 8.42; 95% CI: [2.76-25.69];
      adjusted p value <0.001), and fewer blood transfusions (adjusted mean difference:
      4.98; 95% CI: [0.14-9.82]; adjusted p value = 0.046) than the OR group. Among the
      115 patients without major extrathoracic injuries, higher mortality and higher
      transfusion requirements were also found in the OR group (adjusted odds ratio for
      mortality: 13.08; 95% CI [2.53-67.53], adjusted p value = 0.002 and adjusted mean
      difference in transfusion units: 4.45; 95% CI [1.39-7.51]; adjusted p value =
      0.004). Among the 74 patients with major extrathoracic injuries, significantly
      higher mortality and pneumonia rate were found in the OR group (adjusted p values
      0.04 and 0.03, respectively). Multivariate analysis showed that centers with high
      volume of endovascular procedures had significantly fewer systemic complications
      (adjusted p value 0.001), fewer local complications (adjusted p value p = 0.033),
      and shorter hospital lengths of stay (adjusted p value 0.005) than low-volume
      centers. CONCLUSIONS: Most surgeons select SG for traumatic thoracic aortic
      ruptures, irrespective of associated injuries, injury severity, and age. SG is
      associated with significantly lower mortality and fewer blood transfusions, but
      there is a considerable risk of serious device-related complications. There is a
      major and urgent need for improvement of the available endovascular devices.

PMID- 18332795
TI  - Male gender is associated with excessive IL-6 expression following severe injury.
AB  - OBJECTIVE: An important and persistent laboratory finding has been that males and
      females respond differently after traumatic injury and hemorrhagic shock. We have
      previously presented clinical data showing that male gender is independently
      associated with a 40% higher rate of multiple organ failure (MOF) and a 25%
      higher rate of nosocomial infection (NI) after injury; however, the mechanism
      responsible for this dimorphic response after injury has not been adequately
      characterized clinically. METHODS: Data were obtained from a multicenter
      prospective cohort study evaluating clinical outcomes in severely injured adults
      with blunt hemorrhagic shock. Proteomic analysis of serum inflammatory cytokines,
      on days 0, 1, and 4 postinjury, was performed on 46 males and 34 females.
      Repeated measures ANOVA were used to compare serial IL-1beta, TNF-alpha, IL-6, IL
      8, and IL-10 serum levels across gender, while controlling for important
      confounders. Logistic regression modeling was then used to analyze the
      independent risk of MOF and NI associated with gender. RESULTS: IL-6 serum levels
      were statistically higher in males relative to females (p = 0.008). This higher
      level of IL-6 expression in males remained statistically significant over time
      even after controlling for differences in age, initial base deficit, ISS, and 12
      hour blood transfusion requirements (p = 0.025). No differences in IL-1beta serum
      levels (p = 0.543), TNF-alpha, (p = 0.200) IL-8 (p = 0.107), and IL-10 (p =
      0.157) were found. Males had a higher crude incidence of MOF and an 11-fold
      higher independent risk of MOF. CONCLUSIONS: Persistently elevated IL-6 levels in
      males are associated with a higher rate of MOF. It is not known if this excessive
      IL-6 expression in males is causal or only a marker for poor outcome. Further
      studies are required to elucidate if this early, persistent IL-6 expression is
      responsible for the gender-based differential outcomes after injury.

PMID- 18332796
TI  - High levels of endogenous estrogens are associated with death in the critically
      injured adult.
AB  - BACKGROUND: Sex hormones exhibit predictable changes in their physiologic
      patterns during critical illness. Endogenous estrogens are elevated in both
      genders as a result of the peripheral conversion of androgens to estrogens by the
      aromatase enzyme. Elevated endogenous estrogens have been associated with death
      in medical and mixed surgical intensive care unit (ICU) patients. Our objective
      was to determine the relationship between endogenous estrogens and outcomes in
      critically injured patients. METHODS: A prospective cohort of injured patients
      remaining in the ICU for at least 48 hours at two trauma centers was enrolled.
      Sex hormones (estradiol, progesterone, testosterone, prolactin, and
      dehydroepiandrosterone-sulfate) were assayed and mortality was assessed. A
      logistic regression model was used to determine the association between estradiol
      and death. The area under the receiver operating characteristic (AUROC) curve was
      used to estimate the accuracy of estradiol in predicting death. RESULTS: Nine
      hundred ninety-one patients were enrolled with a 13.4% mortality rate. Despite no
      detectable difference in mortality among genders, estradiol was significantly
      elevated in nonsurvivors (16 pg/mL vs. 35 pg/mL, p < 0.001). Estradiol was a
      marker for injury severity with the most severely injured patients exhibiting the
      highest levels. The ability of estradiol to predict death (AUROC = 0.65) was
      comparable with Trauma and Injury Severity Score (AUROC = 0.65) and superior to
      Injury Severity Score (AUROC = 0.54) in this cohort. CONCLUSIONS: Serum estradiol
      is a marker of injury severity and a predictor of death in the critically injured
      patient, regardless of gender. Whether or not estradiol plays a causal role in
      outcomes is unclear, but estrogen modulation represents a potential therapy for
      improving outcomes in critically ill trauma patients.

PMID- 18332797
TI  - Systemic ubiquitin release after blunt trauma and burns: association with injury
      severity, posttraumatic complications, and survival.
AB  - BACKGROUND: Recent data suggest that ubiquitin (Ub) is systemically released
      after trauma, has pleiotropic effects on host defense mechanisms, and that Ub
      administration reduces fluid shifts into tissues during inflammation. Ub release
      after burns (B) has not been studied and its association with injury severity and
      outcome after blunt trauma (T) is unknown. Thus, we evaluated Ubs association
      with injury severity and outcomes after B and T. METHODS: Injury severity was
      assessed with the Injury Severity Score (ISS) in T and burn size (% total body
      surface area, %TBSA) in B. A total of 129 T (ISS: 26 +/- 13) and 55 B (46% +/-
      18% TBSA) were observed for sepsis/multiple organ failure (MOF) and survival. In
      B, sequential organ failure assessment scores were documented daily. Fifty
      volunteers served as controls (C) Ub serum levels were measured on day 0
      (admission), 1, 3, 5, and 7 by enzyme-linked immunosorbent assay. Data were
      analyzed using bivariate or partial correlation analyses, t test, and analysis of
      variance with Tukey post-hoc test for multiple comparisons (two-tailed p < 0.05).
      RESULTS: Ub was significantly elevated in patients. Peak levels (ng/mL) were
      detectable on day 0 (C: 118 +/- 76; T: 359 +/- 205; B: 573 +/- 331) and increased
      with increased ISS, %TBSA, and presence of inhalation injury. In T, Ub normalized
      by day 3, but remained elevated in B. In B, Ub correlated significantly negative
      with sequential organ failure assessment scores (r: -0.143; p = 0.0147),
      sepsis/MOF development (r: -0.363; p = 0.001), and survival (r: -0.231; p =
      0.009). Compared with B who recovered uneventfully, Ub levels were significantly
      lower on days 1 to 7 and on days 5/7 in B who developed sepsis/MOF or died,
      respectively. CONCLUSION: Ub concentrations reflect the extent of tissue damage.
      Along with Ubs previously described anti- inflammatory properties, this study
      suggests that its systemic release is protective, that burn patients who develop
      sepsis/MOF have a relative Ub deficiency and that Ub could play an important role
      during the physiologic response to burn injury.

PMID- 18332798
TI  - Trauma quality improvement using risk-adjusted outcomes.
AB  - PURPOSE: The National Surgical Quality Improvement Program has improved the
      quality of surgical care by tracking risk-adjusted patient outcomes. Unlike the
      National Surgical Quality Improvement Program, the trauma center verification
      program of the American College of Surgeons (ACS) focuses on availability of
      optimal resources, not outcomes. We hypothesized that significant variations in
      outcomes exist across similar level ACS-verified trauma centers despite
      availability of similar resources. METHODS: The National Trauma Data Bank was
      used to identify adult patients (age 16-99 years) who were treated at ACS
      verified Level I trauma centers that submitted at least 1,000 patients during the
      5-year study period (264,102 patients from 58 trauma centers, excluding dead upon
      arrival). Multivariate logistic regression was used to analyze expected survival
      for each patient, adjusted for age, gender, race, injury mechanism, transfer
      status, and injury severity. Observed-to-expected survival ratios (O/E ratios
      with 95% confidence intervals) were used to rank trauma centers as high
      performers (O/E ratio significantly larger than 1), low performers (O/E ratio
      significantly less than 1), or average performers (O/E ratio overlapping 1).
      RESULTS: Almost half the centers performed significantly different from their
      risk-adjusted expectation. Fourteen were high performers, 11 were low performers,
      and 33 were average performers. CONCLUSIONS: The trauma center verification
      process in its present form may not ensure optimal outcome across all verified
      centers. If further validated, these findings suggest significant room for trauma
      quality improvement by replicating structures and processes of high performing
      trauma centers.

PMID- 18332799
TI  - Malpractice risk: trauma care versus other surgical and medical specialties.
AB  - BACKGROUND: Medical malpractice has been noted to play an important role in
      physicians' decisions to pursue or remain in certain presumed high-risk
      specialties such as trauma surgery, despite little evidence suggesting an
      elevated malpractice risk. The objective of this study was to compare the
      malpractice experience for trauma care and other medical and surgical specialties
      at an academic medical center. METHODS: Information regarding all potentially
      compensable medical events (hereafter "events") and actual lawsuits that occurred
      between 2003 and 2006 at one academic medical institution, including the
      department or service primarily involved, the current medical-legal disposition
      of the event, and the actual or expected expenses was obtained. The number of
      patients admitted to each service and the time they spent in the hospital was
      also obtained, and the number of events per capita and length of stay was
      calculated. RESULTS: Among the 13 medical and surgical specialties considered,
      there were 194 total events, 183,392 patients seen, and 757,880 days of
      hospitalization. The trauma service had the fewest events and lawsuits per 10,000
      patient-days and ranked 10th (11th for lawsuits) on a per capita basis, and 9th
      in total estimated cost. CONCLUSIONS: With the fewest events and lawsuits per
      patient days and a relatively low amount set aside for claims, trauma care has
      better claim experience than almost every other clinical service line. Although
      these results have some limitations, they refute the perception that trauma care
      is a higher medicolegal risk. This observation should not be cited as a
      disincentive for surgeons to provide trauma care.

PMID- 18332800
TI  - The effect of reclined seats on mortality in motor vehicle collisions.
AB  - BACKGROUND: Motor vehicle collisions are the leading cause of trauma-related
      death in the United States. Reclined seatbacks may alter crash kinetics and
      affect occupant outcome. We examined the effect of reclined seatbacks on occupant
      mortality. METHODS: Our study population consisted of United States traffic
      crashes from 1995 to 2005, using data from the Crash Injury Research and
      Engineering Network and the National Automotive Sampling System Crashworthiness
      Data System. Phase 1, we performed a detailed review of crash kinetics and
      biomechanical factors resulting in injury patterns in fully reclined occupants.
      Phase 2, we performed a population-based retrospective cohort study comparing
      outcome in upright, partial, and full recline positions. Primary outcome measure
      was 30-day mortality. RESULTS: Phase 1, flexion and compression injuries over
      pretensioned lap and shoulder belts resulted in severe thoracoabdominal and spine
      injuries in restrained occupants, with a high associated mortality. Increased
      lower extremity injuries from additional force loads into bolsters and panels
      were also noted. Phase 2, the majority (>50%) of front-seat occupants was
      partially reclined. Fully reclined occupants were younger (30 vs. 39 years, p <
      0.0001), more likely to be male (70% vs. 49%, p < 0.0001) and less likely to wear
      a seat belt (58% vs. 78%, p < 0.0001) than upright or partially reclined
      occupants. Mortality was increased in both partially (adjusted odds ratio 1.15,
      95% confidence interval 1.05-1.26) and fully reclined occupants (adjusted odds
      ratio 1.77, 95% confidence interval 1.09-2.88). CONCLUSION: The reclined position
      is associated with increased occupant mortality in motor vehicle collisions.

PMID- 18332801
TI  - Recombinant factor VIIa: decreasing time to intervention in coagulopathic
      patients with severe traumatic brain injury.
AB  - BACKGROUND: Treatment of coagulopathy is often needed before neurosurgical
      intervention in patients with traumatic brain injury (TBI). Typically, this is
      accomplished with administration of plasma. We hypothesized that the off-label
      use of recombinant factor VIIa (rFVIIa) to normalize the coagulation profile
      would allow for earlier intervention than conventional therapy. METHODS: The
      trauma registry was used to identify patients with severe TBI who were admitted
      during a 4-year period and were coagulopathic at admission (international
      normalized ratio, INR >/=1.4) and required a neurosurgical procedure. Severe TBI
      was defined as head abbreviated injury scale (AIS) >3 and admission Glasgow coma
      score (GCS) <9. Demographics, injury, blood bank and laboratory data, time of
      intervention, rFVIIa use, and complications were abstracted. Characteristics of
      the group who received rFVIIa were compared against those treated with plasma
      alone with a Student's t test and chi analysis, as well as nonparametric methods
      for comparison of medians. RESULTS: Of 681 patients with severe TBI, 63 were
      coagulopathic at admission and needed an emergent neurosurgical procedure. Twenty
      nine patients who received rFVIIa were compared against 34 patients who were
      treated with only plasma. Mean age, injury severity score (ISS), and admission
      GCS and INR were not different between the two groups. Time to neurosurgical
      intervention was less in the rFVIIa group (median = 144 vs. 446 minutes, p =
      0.0003) as were the number of units of plasma administered before intervention
      (median = 2 vs. 6, p = 0.0006). The rate of thromboembolic complications was not
      different between groups. In patients with isolated TBI, mortality was 33.3% in
      the rFVIIa group and 52.9% in controls (p = 0.24). CONCLUSION: rFVIIa rapidly and
      effectively reversed coagulopathy in patients with severe TBI. rFVIIa decreased
      the time to intervention and decreased the use of blood products without
      increasing the rate of thromboembolic complications.

PMID- 18332802
TI  - Surviving blood loss without fluid resuscitation.
AB  - BACKGROUND: Patients with massive blood loss often die before delivery of
      definitive care, especially in austere environments. Strategies that can maintain
      life during evacuation and transport to higher levels of care may be lifesaving.
      We have previously shown that administration of histone deacetylase inhibitors
      (HDACI) enhance gene transcription through specific modifications of DNA
      associated histone proteins. Furthermore, it protects against organ damage when
      given before hemorrhage. The current experiment was done to test whether
      administration of HDACI after lethal hemorrhage, without fluid resuscitation,
      would improve outcome by creating a pro-survival phenotype. METHODS: Seventy-two
      male Wistar-Kyoto rats (n = 12 per group) were subjected to 60% blood volume loss
      for 1 hour (40% arterial bleed for 10 minutes and 20% venous bleed for 50
      minutes). After hemorrhage, animals were randomized to receive one of two HDACI:
      (1) valproic acid (VPA, 300 mg/kg in 0.25 mL saline), or (2) suberoyanilide
      hydroxamic acid (SAHA, 7.5 mg/kg in 0.25 mL saline). Control groups included (3)
      no hemorrhage (Sham), (4) no resuscitation (NR), (5) 0.9% saline resuscitation, 3
      times the volume of shed blood (NS), and (6) vehicle control, 0.25 mL 0.9% saline
      (VEH). Hemodynamic data were recorded continuously, and physiologic parameters
      were measured serially. Survival for 3 hours was the primary endpoint for this
      experiment. RESULTS: Nonresuscitated shock (NR group) was highly lethal and only
      25% of the animals survived for 3 hours. Administration of HDACI after hemorrhage
      (without fluid resuscitation) significantly improved survival (75% and 83% in VPA
      and SAHA groups, respectively, p < 0.05 vs. NR). Survival was 40%, 100%, and 100%
      in the VEH, Sham, and NS resuscitation groups, respectively. CONCLUSIONS: This
      study demonstrates that post-shock administration of HDACI can significantly
      improve early survival in a highly lethal model of hemorrhagic shock, even in the
      absence of conventional fluid resuscitation. This approach may be especially
      relevant for austere environments where fluids are in limited supply, such as a
      battlefield.

PMID- 18332803
TI  - Regional and local brain oxygenation during hemorrhagic shock: a prospective
      experimental study on the effects of small-volume resuscitation with
      norepinephrine.
AB  - BACKGROUND: Patients with uncontrolled hemorrhage may benefit if resuscitation
      with large amounts of fluids is replaced by a small volume or vasopressor until
      surgery. Norepinephrine (NE) is commonly used as a vasopressor to control
      hypotension. The purpose of this study was to compare the effects of hypertonic
      hyperoncotic saline starch solution (HHS) either alone or combined with NE on
      brain tissue oxygen pressure (PbtO2) and brain oxygen saturation (rSO2) in a
      model of uncontrolled hemorrhage. METHODS: After approval of the animal
      investigation committee, 22 anesthetized pigs underwent simulated penetrating
      liver trauma. At hemodynamic decompensation, animals were randomly assigned to
      receive HHS (Hyperhaes; 4 mL/kg; n = 8) with normal saline placebo, low-dose NE
      (low NE; 500 microg, and 1 microg/kg/min; n = 7), or high-dose NE (high NE; 1,000
      microg, and 1 microg/kg/min; n = 7). Bleeding was controlled manually 30 minutes
      after drug administration. RESULTS: Cerebral perfusion pressure (CePP), PbtO2,
      and rSO2 decreased with hemorrhage in all groups (baseline vs. decompensation,
      CePP-HHS, 83 +/- 5 mm Hg vs. 9 +/- 1 mm Hg; low NE, 67 +/- 6 mm Hg vs. 16 +/- 2
      mm Hg; high NE, 77 +/- 7 mm Hg vs. 15 +/- 1 mm Hg. PbtO2-HHS, 100% vs. 29%; low
      NE, 100% vs. 33%; high NE, 100% vs. 27%. rSO2-HHS, 100% vs. 70%; low NE, 100% vs.
      76%; high NE, 100% vs. 63%). Therapy with HHS, low NE, and high NE resulted in a
      comparable increase of CePP, PbtO2, and rSO2, respectively (5 minutes after
      therapy, CePP-HHS, 29 +/- 3 mm Hg; low NE, 27 +/- 3 mm Hg; high NE, 28 +/- 3 mm
      Hg. PbtO2-HHS, 207%; low NE, 129%; high NE, 170%. rSO2-HHS, 94%; low NE, 83%;
      high NE, 87%). Overall survival was six of eight, four of seven, and six of
      seven, respectively. CONCLUSION: After uncontrolled hemorrhagic shock, addition
      of different dosages of NE to HHS, compared with HHS alone, showed no beneficial
      effect on CePP, rSO2, or PbtO2.

PMID- 18332804
TI  - The use of a powered device for intraosseous drug and fluid administration in a
      national EMS: a 4-year experience.
AB  - BACKGROUND: Provide evidence of success rate and limitations of the prehospital
      use of a powered device for intraosseous (IO) bone infusion, the bone injection
      gun (BIG) for critical patients in whom peripheral intravenous (IV) access cannot
      be readily obtained. METHODS: This prospective study included all reports
      regarding the use of BIG in our national EMS during the study period. The BIG is
      a FDA and Israeli Health ministry approved device for IO cannulation. Starting
      April 2000, a new version was introduced to all ALS units. Simultaneously, our
      medical protocols were updated to include its use and mandatory reporting was
      initiated. Successful insertion was defined as "obtaining a good fluid flow
      through the needle without evidence of extravasation". This article presents an
      analysis of the data collected during this period. RESULTS: From May 2000 to June
      2004, 189 patient encounters in which the BIG was employed met inclusion criteria
      and comprised the study group. Successful insertion on first attempt was achieved
      in 172 patients (91.0%). In two additional patients, a second attempt was
      successful. Forty-seven of the patients were below the age of 18 years (24.9%).
      One hundred ten patients (58.2%) were over 60 years of age. One hundred thirty
      three were found without a palpable pulse (70.4%), and only 18 were found with a
      Glasgow coma scale of 9 or above. The cause was traumatic in 34 patients (18.0%).
      CONCLUSION: The BIG provides an effective alternative IV access for critical
      patients in whom a peripheral IV line cannot be readily obtained in the
      prehospital setting.

PMID- 18332805
TI  - Blunt splenic injuries: have we watched long enough?
AB  - BACKGROUND: Nonoperative management (NOM) of blunt splenic injuries (BSIs) has
      been used with increasing frequency in adult patients. There are currently no
      definitive guidelines established for how long BSI patients should be monitored
      for failure of NOM after injury. METHODS: This study was performed to ascertain
      the length of inpatient observation needed to capture most failures, and to
      identify factors associated with failure of NOM. We utilized the National Trauma
      Data Bank to determine time to failure after BSI. RESULTS: During the 5-year
      study period, 23,532 patients were identified with BSI, of which 2,366 (10%
      overall) were taken directly to surgery (within 2 hours of arrival). Of 21,166
      patients initially managed nonoperatively, 18,506 were successful (79% of all
      comers). Patients with isolated BSI are currently monitored approximately 5 days
      as inpatients. Of patients failing NOM, 95% failed during the first 72 hours, and
      monitoring 2 additional days saw only 1.5% more failures. Factors influencing
      success of NOM included computed tomographic injury grade, severity of patient
      injury, and American College of Surgeons designation of trauma center.
      Importantly, patients who failed NOM did not seem to have detrimental outcomes
      when compared with patients with successful NOM. No statistically significant
      predictive variables could be identified that would help predict patients who
      would go on to fail NOM. CONCLUSIONS: We conclude that at least 80% of BSI can be
      managed successfully with NOM, and that patients should be monitored as
      inpatients for failure after BSI for 3 to 5 days.

PMID- 18332806
TI  - Multidetector-row computed tomography (CT) of blunt pancreatic injuries: can
      contrast-enhanced multiphasic CT detect pancreatic duct injuries?
AB  - BACKGROUND: We examined patients of blunt trauma with contrast-enhanced
      multiphasic computed tomography (CT) and determined if it could detect pancreatic
      duct injuries. METHODS: During a 17-month period, 95 patients of blunt abdominal
      trauma underwent multiphasic CT examinations. The CT grading scales of pancreatic
      injuries at parenchymal phase, portal venous phase, and equilibrium phase were
      recorded and compared with surgery, endoscopic retrograde
      cholangiopancreatography, or discharged diagnosis. The diagnostic values of
      multiphasic CT and interobserver agreements at different phases were computed.
      RESULTS: Of the 95 patients, nine (9.5%) had pancreatic injuries (six with main
      duct injuries, three without main duct injuries). The interobserver agreement
      presented in kappa values between two radiologists regarding the integrity or
      disruption of the main duct were good at parenchymal phase (K = 0.73), portal
      venous phase (K = 0.64), and equilibrium phase (K = 0.68). The overall accuracies
      of multiphasic CT in detecting main duct injuries were 97.9% (parenchymal phase),
      100.0% (portal venous phase), and 96.8% (equilibrium phase), respectively. The
      sensitivity (50.0%) and negative predictive value (96.7%) of equilibrium phase CT
      were the lowest among the three phases of CT scans. CONCLUSION: The portal venous
      phase CT was the most accurate scan to detect pancreatic duct injuries. However,
      equilibrium phase CT might underestimate major pancreatic injuries. Multiphasic
      CT shows early promise in this clinical application and further multi
      institutional studies to verify its accuracy and reveal the optimal CT
      methodology are needed.

PMID- 18332807
TI  - Broken bones and orthopedist groans: can an acute care surgeon fix both?
AB  - BACKGROUND: Increasing reluctance of specialty surgeons to participate in trauma
      care has placed undue burden on orthopedic traumatologists at Level I trauma
      centers and prompted the exploration of an expanded role for general trauma
      surgeons in the initial management of select orthopedic injuries (OI) as an acute
      care surgeon. This study characterizes OI sustained by trauma patients (TPs) to
      analyze the feasibility of this concept. METHODS: The National Trauma Data Bank
      was queried for specific information relating to the profile of OI. International
      Classification of Diseases-9th Revision codes were used to select patients for
      the study who sustained OI alone or in combination with other injuries as well as
      to determine body region of injury and a status of open or closed fractures.
      Skeletal Abbreviated Injury Scale scores were used to determine the severity of
      fractures, and International Classification of Diseases-9th Revision procedure
      codes were used to identify the nature of initial operative management. RESULTS:
      Of the 1,130,093 patients studied, 557,541 (49%) had one or more reported OI.
      Open injuries constituted 11.4% of all OIs and occurred in 7.5% of all TPs.
      Distribution of OIs was 23% upper extremity (18% open) and 35% lower extremity
      (also 18% open). These represent a 15% and 22% occurrence in TP. Pelvic and
      acetabular fractures occurred in 13% of OI patients (4% open) and 6% of all TP.
      The mean skeletal Abbreviated Injury Scale of all OIs was 2.3. For upper
      extremities it was 2.2, for lower extremities and for pelvic or acetabular
      injuries it was 2.4. Closed reduction of joint dislocation was performed in 2% of
      OI and 1% of all TPs. Of these, 45% were on the hip, 8% on the knee, 15% on the
      ankle, 13% on the elbow, and 20% on the shoulder. The distribution of initial
      interventions for all patients with OI was irrigation and debridement (I&D) 13%,
      external fixator (ex-fix) application 25%, closed reduction 41%, and closed joint
      relocation 10%. Of all open injuries, 17% underwent I&D and 31% underwent ex-fix
      application. The median time to I&D or ex-fix application was 7.2 hours. One
      percent of these procedures were performed within 1 hour of hospital admission,
      11% within 6 hours of hospital admission. CONCLUSION: OI occur in a significant
      portion of TP reported to the National Trauma Data Bank. They most commonly
      involve the lower extremities and are of moderate severity. Given this profile,
      it seems feasible to propose that some initial procedures can be mastered by
      nonorthopedic surgeons and that select OI management be within the purview of a
      properly trained and credentialed acute care surgeon.

PMID- 18332808
TI  - Gastric alkalinization after major trauma.
AB  - BACKGROUND: Gastric function in trauma patients is poorly understood. In animals,
      shock causes gastric luminal alkalinization and bile reflux. In trauma patients,
      studies of stress gastritis prophylaxis demonstrated with continuous gastric pH
      monitoring that the stomach became alkaline even without antisecretory therapy.
      Therefore, we hypothesized that trauma patients have an alkaline gastric
      environment that may be because of bile reflux. METHODS: A prospective
      observational study at an urban Level I trauma center was performed. All major
      torso trauma patients (severe head injuries excluded) who met the criteria for
      standardized shock resuscitation were eligible for inclusion. A 12.5 Fr silastic
      pH probe (Sandhill Scientific) was placed in the stomach and the gastric pH
      continuously monitored for 7 days. Patients received no stress gastritis
      prophylaxis. Gastric samples were obtained each day and assayed for total bile
      acids and pH. RESULTS: Twelve patients were entered into the study. Mean age was
      31 years +/- 4 years, 67% men, 75% blunt mechanism of injury, and mean Injury
      Severity Score 28 +/- 3. Three patients (25%) developed multiple organ failure
      and four acquired ventilator-associated pneumonia. During the first day of
      continuous pH monitoring, 9 of 12 patients had a gastric pH >4 for the majority
      of the day with 7 patients having essentially no acid production. During
      subsequent days, gastric pH began to drop and by the 4th day the majority of each
      day was spent at a pH <4. Additionally, gastric pH of patients with ventilator
      associated pneumonia or multiple organ failure tended to be more alkaline. Bile
      acid was present in the gastric fluid of all patients in varying amounts.
      However, there was no significant correlation between gastric pH and bile acid
      concentration. CONCLUSIONS: Traumatic injury causes gastric luminal
      alkalinization that may be related, only in part, to bile acid reflux. Other
      alkalinizing factors remain to be elucidated.

PMID- 18332809
TI  - Can cerebral hypoperfusion after sympathetic storm be used to diagnose brain
      death? A retrospective survey in traumatic brain injury patients.
AB  - BACKGROUND: The aim of this study was to identify the precise time of occurrence
      of irreversible coma from brain stem dysfunction that precedes brain death.
      Sympathetic storm, which is a cardiovascular hyperdynamic state manifested by
      brain stem ischemia, is known to be related to brain stem failure in animal
      models. We studied sympathetic storm in the clinical setting and compared the
      clinical findings observed before and after sympathetic storm to identify the
      precise time of occurrence of irreversible apneic coma. METHODS: We conducted a
      retrospective study of 15 comatose traumatic brain injury adult patients at the
      National Taiwan University Hospital's Neurosurgical Intensive Care Unit. Data on
      arterial blood pressure, heart rate, intracranial pressure, and clinical findings
      such as cerebral blood flow pattern, Glasgow Coma Scale, brain stem reflexes,
      utilizations of catecholamines, and occurrence of central diabetes insipidus
      throughout the course in the intensive care unit were collected retrospectively
      from medical records. RESULTS: Prolonged uncorrectable cerebral hypoperfusion was
      found after a characteristic irreversible apneic coma-associated sympathetic
      storm (IACASS) in all 15 patients. A mean cerebral perfusion pressure of 11.9 mm
      Hg +/- 10.3 mm Hg and 13 mm Hg +/- 3.5 mm Hg remained at 12 hours and 24 hours,
      respectively, after IACASS. Differences in clinical findings before and after
      IACASS that were statistically significant were cerebral circulation pattern (p =
      0.0455), Glasgow Coma Scale (p = 0.0143), brain stem reflexes (p = 0.0143),
      utilization of catecholamines (p = 0.0254), and occurrence of central diabetes
      insipidus (p = 0.00468). CONCLUSIONS: Coma might have become irreversible
      immediately after IACASS because the prolonged duration of cerebral hypoperfusion
      could have caused irreversible cerebral tissue injury. Our study provides some
      preliminary findings suggesting that IACASS may be a predictor of impending brain
      death. A prospective study is the next step to understanding whether this
      phenomenon can be applied clinically to diagnose irreversible apneic coma.

PMID- 18332810
TI  - Generation of procoagulant microparticles in cerebrospinal fluid and peripheral
      blood after traumatic brain injury.
AB  - BACKGROUND: Traumatic brain injury (TBI) can induce cell damage. Procoagulant
      microparticles (MPs) are reliable markers of cell stimulation. The aim of this
      study was to investigate the generation of procoagulant MPs in the cerebrospinal
      fluid (CSF) and plasma of patients with severe TBI. MATERIAL: CSF and plasma MPs
      of 16 patients with severe TBI were quantified by functional prothrombinase assay
      (i) on the day of the trauma, (ii) during a 10-day follow-up and compared with
      control samples. The cellular origin of MP was determined after capture with
      specific antibodies. RESULTS: The CSF and plasma of patients with severe TBI
      revealed a significantly increased generation of MP compared with control samples
      on the day of the trauma (CSF: 4.5 +/- 1.8 vs. 0.83 +/- 0.28 nanomolar PhtdSer
      equivalent; p = 0.01 and plasma 4.1 +/- 3.7 vs. 2.3 +/- 0.19 nanomolar PhtdSer
      equivalent; p = 0.02). Procoagulant MPs were mainly of platelet and endothelial
      origin in CSF. MPs decreased significantly in the CSF 10 days after TBI. In CSF,
      a sustained generation of procoagulant MP was evidenced in two patients
      presenting a poor clinical outcome. In the blood flow, elevated amounts of
      procoagulant MPs were detected in three patients presenting disseminated
      intravascular coagulopathy during the follow-up. CONCLUSION: Procoagulant MP
      testifying to platelet and endothelial activation are produced in the CSF and in
      the plasma after severe TBI. A sustained generation of procoagulant MP in the CSF
      could contribute to a poor clinical outcome.

PMID- 18332811
TI  - Traumatic subdural hygromas: proposed pathogenesis based classification.
AB  - BACKGROUND: Traumatic subdural hygroma (TSHy) is an accumulation of cerebrospinal
      fluid (CSF) in the subdural space after head injury. It appears to be relatively
      common, but its onset time and natural history are not well defined. Considered a
      benign epiphenomenon of trauma, the pathogenesis of TSHy is still unclear and
      many questions remain unanswered. This study adds to the information on TSHy, and
      proposes a classification based on pathogenesis. METHODS: Thirty-four consecutive
      adult patients with TSHy were analyzed for clinical evolution and serial CT scan,
      during a period of several months. TSHy diagnosis was based on published CT scan
      criteria of hypodense subdural collection after trauma, without enhancement and
      neomembrane, with a minimum distance of 3 mm between the skull and brain.
      Ventricle size was analyzed by calculating the bicaudate index (BCI). For
      comparison, the BCI was measured from CT scan at three moments: admission, at
      time of TSHy diagnosis, and from last CT scan. RESULTS: There were 34 patients,
      aged between 16 and 85 years (mean 40), half of them were below 40 years. Road
      traffic crashes were the main cause of head injury. The mean time for hygroma
      diagnosis was 9 days. Twenty-one patients (61.8%) underwent conservative
      treatment for TSHy and 13 (38.2%), surgical treatment. TSHy are early lesions and
      can be detected in the first 24 hours after trauma, usually as small subdural
      effusion (SSEff). Based on clinical and CT scan findings, we divided the 34
      patients into 3 groups, (Ia and Ib) without evident mass effect and (II) with
      evident mass effect. Group Ia includes patients without ventricle dilation; Ib,
      patients with associated ventricle dilations. CONCLUSIONS: SSEff detected in the
      first 24 hours posttrauma in our series evolved into TSHy suggesting that this is
      an early lesion; all THSy were divided in three groups according to the
      pathophysiologic mechanism. These three groups probably represent a continuum of
      CSF absorption impairment. Group Ia represents what most authors consider a
      simple hygroma, with no impairment on CSF absorption. Group Ib represent the
      external hydrocephalus form with various degrees of CSF imbalance, and group II
      were the cases presenting marked mass effect.

PMID- 18332812
TI  - Differences in early- and late-onset ventilator-associated pneumonia between
      surgical and trauma patients in a combined surgical or trauma intensive care
      unit.
AB  - INTRODUCTION: Ventilator-associated pneumonia (VAP) is a leading cause of
      morbidity in the perioperative period. Based on differences in causes, VAP has
      been divided into early (</=96 hours of admission) and late (>96 hours of
      admission) onset. We sought to compare differences in patient characteristics and
      outcome between early- and late-onset VAP in trauma and nontrauma surgical
      patients. METHODS: A retrospective analysis of prospectively collected data were
      performed for all surgical and trauma patients admitted to the surgical or trauma
      intensive care unit of an academic medical center from December 1996 to March
      2005 who developed VAP. Patients with early- and late-onset VAP were compared
      with regard to patient characteristics, cause, and outcome using bivariate and
      multivariate analyses. RESULTS: Three hundred thirty VAPs were identified in 233
      trauma (71%) and 97 nontrauma surgery patients (29%). There was no statistically
      significant difference in recurrence, mortality, or length of stay between early-
      and late-onset VAP in trauma patients. Mortality for late- onset VAPs in
      nontrauma patients was 44% versus 23% for early-onset VAPs (p = 0.09). On a per
      case basis, trauma patients had significantly better mortality (11% vs. 41%) and
      length of stay (33.1 +/- 1.4 vs. 55.8 +/- 4.1 days) than nontrauma surgical
      patients with VAP (p < 0.0001), although the rate of VAP-related death favored
      the nontrauma patients (1.8 deaths of 100 intensive care unit trauma admissions
      vs. 1.1 deaths of 100 intensive care unit nontrauma admissions, p = 0.05).
      CONCLUSIONS: Although there is a trend toward worse outcome in nontrauma patients
      with late-onset VAP, trauma patients with late- and early-onset VAP behave
      similarly. On a per case basis, trauma patients have significantly better
      outcomes than nontrauma surgical patients with VAP when cared for within the same
      surgical or trauma intensive care unit.

PMID- 18332813
TI  - Posttraumatic and postoperative cardiac luxation: computed tomography findings in
      nine patients.
AB  - BACKGROUND: Posttraumatic and postoperative cardiac luxation represents a serious
      complication of pericardial rupture, and early diagnosis is important. The
      purpose of this study is to determine signs of left cardiac luxation on computed
      tomography (CT). METHODS: CT scans in nine patients with pericardial rupture and
      cardiac luxation after blunt chest trauma (n = 7) and postoperatively after
      extended left pneumectomy (n = 2) were reviewed for abnormalities. We analyzed
      the clinical history, clinical findings, and the imaging findings. RESULTS:
      Dislocation of the heart to the left and pneumopericardium were seen in nine
      patients. Five of these nine patients revealed "entrapment" of the left heart
      between the proximal ascending aorta and the descending aorta. All patients
      underwent a pneumopericardium. All patients with a history of trauma showed a
      left-sided pneumothorax but no pericardial effusion. CONCLUSIONS: CT plays a key
      role for early diagnosis of cardiac luxation. Dislodgment of the heart,
      entrapment of the left atrium and ventricle, and pneumopericardium associated
      with pneumothorax are the most important CT findings.

PMID- 18332814
TI  - Pregnant women injured in terror-related multiple casualty incidents: injuries
      and outcomes.
AB  - OBJECTIVE: To characterize the injuries incurred by involvement in terror-related
      multiple casualty incidents (TR-MCIs) during pregnancy and describe the maternal
      and fetal outcomes. METHODS: Retrospective (January 1, 2001-December 31, 2003),
      descriptive, multicenter study of all pregnant women injured in TR-MCIs. RESULTS:
      Twelve pregnant women (singletons, gestational age 20.6 +/- 10.5 weeks) who were
      injured during the study period. One victim was intubated on location of the
      event, another was hemodynamically compromised upon arrival. All women survived.
      Seven women required surgical intervention with general anesthesia. Four of the
      five women with viable pregnancies required cesarean delivery within minutes to
      hours of arrival. Three of these fetuses were delivered in extremis and one died.
      CONCLUSIONS: Women with a viable pregnancy who have been injured in TR-MCIs have
      a high incidence of surgical procedures and a high likelihood of undergoing
      cesarean delivery within minutes to hours of injury. Fetal outcome may be poor
      under these circumstances.

PMID- 18332815
TI  - Activities of xanthine oxidase and superoxide dismutase enzymes in rat intestinal
      tissues in sepsis.
AB  - BACKGROUND: The aim of this study was to elucidate a possible source of oxidant
      stress in experimental sepsis. METHODS: For this aim, 32 Sprague-Dawley type rats
      were used in the study. After all the animals underwent laparotomy, nonlethal
      cecum ligation and puncture (CLP) technique was used to create an experimental
      sepsis model in two groups (CLP-6 and CLP-48 groups). Rats in the other groups
      (Sham operated) were used as controls. Animals in the control-6 and CLP-6 groups
      were killed 6 hours after the beginning of the study whereas the other animals
      were killed 48 hours after the beginning. Part of the terminal ileum of each
      animal was removed to be used in the measurements of xanthine oxidase and
      superoxide dismutase enzyme activities. RESULTS: Xanthine oxidase activity in the
      CLP-48 group was found to increase significantly as compared with that of the
      control-48 group, but superoxide dismutase activity did not change. No
      significant changes, however, were observed between analysis parameters in the
      terminal ileum tissues when obtained 6 hours after the beginning of sepsis.
      CONCLUSION: Our results suggest that increased xanthine oxidase activity is one
      of the leading factors for the oxidant stress in the late phase of sepsis.

PMID- 18332816
TI  - Treatment of distal femur and proximal tibia fractures with external fixation
      followed by planned conversion to internal fixation.
AB  - PURPOSE: To evaluate healing rates and complications in patients treated with
      temporary external fixation (EF) and subsequent open reduction and internal
      fixation (ORIF) for high-energy distal femur or proximal tibia fractures.
      METHODS: Retrospective analysis of prospectively collected data 1999 to 2005.
      Demographic data and injury severity score were obtained from medical records.
      Factors reviewed included perioperative complications (nonunion, postoperative
      infection, loss of fixation) and time to radiographic and clinical union.
      RESULTS: Forty-seven patients with 16 distal femur and 36 proximal tibia
      fractures were treated using temporary EF. Patients subsequently underwent ORIF
      (mean time from EF to ORIF = 5 days, range 1-23 days). Thirty-five fractures were
      open (Gustilo I = 8, II = 6, IIIA = 3, IIIB = 13, IIIC = 5) and 17 closed. Forty
      patients with 44 fractures reached 1-year follow-up. Of these, 36 patients with
      40 (91%) fractures had healed both radiographically and clinically. The mean
      postoperative follow-up time was 14 months (range 3-68). Eight (16%) deep
      infections occurred, all in open fractures (Gustilo I = 2, IIIB = 3, IIIC = 3),
      with one patient requiring above knee amputation. Other complications included
      one hematoma, two malunions, one fixation failure, and one pin site infection.
      One patient died as a result of a stroke. CONCLUSIONS AND SIGNIFICANCE: Temporary
      bridging EF offers the advantage of early soft tissue and bone stabilization
      without the potential local risks of immediate ORIF in severely injured soft
      tissues, or the potential systemic risks in a severely traumatized patient. The
      16% infection rate in this study, all occurring in open fractures, falls within
      the reported range for grade III open fractures (15%-20%). We conclude that the
      initial treatment of high-energy periarticular knee fractures with bridging EF,
      followed by planned conversion to internal fixation is a safe option in patients
      who are unsuitable for initial definitive surgery.

PMID- 18332817
TI  - Fixation of the femoral condyles: a mechanical comparison of small and large
      fragment screw fixation.
AB  - BACKGROUND: To compare the stability achieved using two 6.5-mm screws versus two
      or four 3.5-mm screws for the fixation of a unicondylar distal femur fracture.
      METHODS: A fracture model was created in femoral synthetic composite bones to
      simulate a lateral femoral condyle fracture (AO/OTA 33-B1). Fixation was
      performed using three different types of screw constructs: 1) two 6.5-mm
      cancellous screws inserted using the lag technique, 2) two 3.5-mm cortical screws
      inserted using the lag technique, and 3) four 3.5-mm cortical screws, with two
      inserted using the lag technique and two as position screws. After reduction and
      fixation, the constructs were axially loaded in a material-testing machine. Main
      outcome measurements were the mean load required to displace the osteotomy site 1
      and 2 mm as well as the mean stiffness of the different fixation methods.
      RESULTS: The 6.5-mm construct required 56% more load to displace the osteotomy
      fragment 1 mm than the two 3.5-mm construct required (p < 0.0001), and 40% more
      load than the four 3.5-mm construct required (p < 0.0001). At loads that caused 2
      mm of osteotomy displacement, these differences increased to 62% (p < 0.0001) and
      48% (p < 0.0001), respectively. The mean loads needed to displace the osteotomy
      site were 28% higher for 1 mm of displacement (p = 0.003) and 27% higher for 2 mm
      of displacement (p = 0.03) for the four 3.5-mm screw construct compared with
      those needed for the two 3.5-mm group. The mean stiffness for the 6.5-mm group
      (1312.5 N/mm) was significantly higher than for the four 3.5-mm construct (784.2
      N/mm; p < 0.0001) and the two 3.5-mm screw construct (409.4 N/mm; p < 0.0001).
      The difference in stiffness between the 3.5-mm groups was significant as well (p
      < 0.0001). CONCLUSION: Stabilization of a unicondylar distal femur fracture with
      two 6.5-mm cancellous screws provides the most rigid and stable fixation. If
      small fragment screws are used, a minimum of four 3.5-mm cortical screws should
      be used to approximate the mechanical stability of two 6.5-mm screws.

PMID- 18332818
TI  - Cervical spine fractures in patients 65 years or older: a 3-year experience at a
      level I trauma center.
AB  - BACKGROUND: Cervical spine fractures in the elderly carry a mortality as high as
      26%. We reviewed our experience to define the level of injury, prevalence of
      neurologic deficits, treatments employed, and the correlation between patients'
      pre- and posthospital residences. Also, we correlated the prevalence of advanced
      directives with length of stay. METHODS: We queried the data collected
      prospectively at an American College of Surgeons verified Level I hospital
      (National TRACS, American College of Surgeons) regarding patients aged 65 years
      or older presenting with cervical spine fractures (International Classification
      of Diseases-9 code 805.X) in calendar years 2000 through 2003. RESULTS: We
      identified 58 patients (ages 65-94). Mortality was 24%. Twelve patients had
      quadriplegia or paraplegia and seven of these patients died. Respiratory failure
      was the primary cause of death. Application of rigid collars and a halo brace
      were the most commonly employed therapies. Mortality rates for halo stabilization
      and rigid collar and halo stabilization were similar (23% vs. 29%). Despite
      having a higher mean Injury Severity Score, the 16 patients with advanced
      directives had an intensive care unit length of stay similar to that of patients
      without advanced directives but a statistically significant shorter overall
      length of stay (13 vs. 6.9 days). Eighteen of 45 patients living at home at the
      time of injury returned home. CONCLUSIONS: Cervical spine injury in the elderly
      does not inevitably relegate patients to a setting of more acute nursing care.
      The health and social factors that allowed many to return to living at home
      warrant investigation, as support of these factors may assist others with this
      injury.

PMID- 18332819
TI  - An assessment of early tracheostomy after anterior cervical stabilization in
      patients with acute cervical spine trauma.
AB  - BACKGROUND: The optimal timing of tracheostomy after anterior cervical spine
      surgery remains controversial because of the potential for deep infection. The
      aims of this study were to compare the infection rates in patients requiring
      tracheostomy who underwent anterior versus posterior cervical spine surgery, and
      to report the timing of tracheostomy tube placement in such patients. METHOD: All
      patients admitted to a referral Intensive Care Unit for spinal trauma from
      January 1998 until May 2005, who underwent surgical stabilization with
      instrumentation and also received a tracheostomy, were retrospectively evaluated
      for demographic data, severity of neurologic injury, and complications including
      infection to a surgical site and timing and type of tracheostomy procedure.
      RESULTS: We identified 71 patients, all who had a diagnosis of acute cervical
      spine injury. Thirty-two (45%) underwent anterior stabilization, 15 (21%) had
      posterior stabilizations, and 24 (34%) required both anterior and posterior
      approaches. The mean time from stabilization to tracheostomy for an anterior
      approach was 3.8 +/- 2.6 days. There was no significant difference in the timing
      of tracheostomy for different surgical approaches. Seventeen patients (25%) had a
      positive culture of their cervical and or tracheostomy incision site. Only one
      patient, however, had infection with the same organism at both the tracheostomy
      site and the anterior stabilization site. Suspected infection was managed with
      antibiotics and no further surgical intervention was required. CONCLUSIONS: Early
      tracheostomy after spinal stabilization is associated with a low risk of
      infection even after the anterior approach.

PMID- 18332820
TI  - Prehospital prediction of the severity of blunt anatomic injury.
AB  - OBJECTIVES: To evaluate the ability of paramedics to predict patients requiring a
      major trauma service. To assess whether paramedic prediction of severity of
      injury to individual body regions is accurate and could add to overall paramedic
      prediction of injury severity. METHODS: Helicopter paramedics in Victoria
      prospectively recorded the severity of injury to the head, thoracic, and abdomen
      regions, and whether the patient required a major trauma service, for primary
      response adult (>15 years) trauma patients. Paramedic predictions of injuries
      were compared with patient outcomes. Major trauma was defined as death in
      hospital; an Injury Severity Score >15; intensive care unit admission >24 hours;
      and urgent surgery. A severe anatomic injury was defined as an Abbreviated Injury
      Scale severity >/=3. The sensitivity, specificity, positive predictive value, and
      negative predictive value were calculated. RESULTS: Two hundred and seven
      patients were enrolled in the study, with 62.3% defined as major trauma. The
      sensitivity of paramedic predictions ranged from 57.6 (95% confidence interval
      [CI]; 45.4-68.9) for the head to 38.5 (95% CI; 22.1-57.9) for the abdomen.
      Specificities ranged from 98.3 (95% CI; 93.5-99.6) for the thorax to 93.5 (95%
      CI; 87.9-96.6) for the head region. The sensitivity and specificity of paramedic
      predictions of a major trauma status were 97.7 (95% CI; 93-99.2) and 28.2 (95%
      CI; 19.3-39.1), respectively. The paramedics correctly categorized all patients
      who were admitted to an intensive care unit, required urgent surgery or died in
      hospital as major trauma. CONCLUSIONS: Paramedics were unable to reliably
      identify severe injury to individual body regions. Sensitivity of paramedic
      judgment of major trauma status was high. Assessment of the severity of injury to
      individual body regions did not appear to improve accuracy.

PMID- 18332821
TI  - Evaluation of a multidisciplinary pediatric mock trauma code educational
      initiative: a pilot study.
AB  - BACKGROUND: Our aim was to develop and evaluate a multidisciplinary pediatric
      mock trauma code orientation program for residents on their pediatric hospital
      rotation. METHODS: A before and after evaluation of trauma team residents from
      various programs was conducted. The 1-hour educational session consisted of a 15
      minute mock trauma code, a debriefing and teaching intervention, and then a new,
      postintervention mock trauma code. Before and after each session, residents
      completed a self-assessment questionnaire. All codes were videotaped and later
      evaluated by two blinded observers using a standardized evaluation tool to assess
      patient management and team functioning. RESULTS: Thirty-seven prequestionnaire
      (pre) and postquestionnaire (post) pairs were completed. Residents reported a
      significant improvement in their (1) comfort in managing pediatric trauma (median
      pre 3, post 5, p < 0.001); (2) understanding of their role on the trauma team
      (median pre 4.5, post 6, p < 0.001); (3) familiarity with the resuscitation room
      (median pre 4, post 5, p = 0.001); (4) comfort with procedural skills (median pre
      4, post 5, p = 0.001); (5) awareness of pediatric trauma resuscitation management
      priorities (median pre 5, post 6, p = 0.007). Postintervention, residents
      reported lower knowledge scores in locating equipment in the resuscitation room
      (p < 0.001). There was no significant difference in team performance on the
      videotaped assessments (premean score = 79.8, postmean score = 79.5).
      CONCLUSIONS: The pediatric mock trauma code educational initiative improved
      residents' self-reported confidence, knowledge, and comfort level in managing
      pediatric trauma. The experience also raised residents' awareness of knowledge
      gaps. We were unable to measure a significant change in team functioning post
      intervention.

PMID- 18332822
TI  - Comparison of injury patient information from hospitals with records in both the
      national trauma data bank and the nationwide inpatient sample.
AB  - BACKGROUND: Administrative and registry databases are useful for researchers
      given their availability and size, yet their limitations for specific
      applications remain undefined. We compared injury records from a large
      administrative database and the National Trauma Data Bank (NTDB) with the goal of
      furthering the understanding of their respective limitations. METHODS: The study
      hospitals had submitted records to both the NTDB and the Nationwide Inpatient
      Sample (NIS) for patients admitted during 2002. Record inclusion criteria for
      comparison included nonelective admissions with a primary diagnosis of injury
      (excluding isolated hip fractures). Numbers of cases and variables common to both
      databases were compared. RESULTS: Twenty-four hospitals had records both in the
      NTDB (24,619 records) and in the NIS (25,586 records). We found less missing cost
      and payer information in the NIS compared with the NTDB (0% and 0.1% vs. 30.5%
      and 24%, respectively), higher mean number of comorbidities per record in the NIS
      (0.77 vs. 0.18), and a lower crude case fatality rate in the NIS (3.5% vs. 5.2%).
      CONCLUSIONS: The main differences between the databases reflected the different
      motives for data collection and the inclusion or exclusion criteria imposed by
      trauma registries. These differences require consideration when using either
      database to investigate injury-related questions.

PMID- 18332823
TI  - An alternative and new approach to free flap in treatment of calcaneal region and
      lower third of the lower extremity reconstruction: reverse flow posterior tibial
      fasciocutaneous skin island flaps.
AB  - BACKGROUND: Fasciocutaneous flaps, whether of the upper or lower extremity, have
      certain distinct advantages. These flaps are very simple to raise, quick to
      execute, and have a high reliability. On the basis of experimental studies, it is
      reasonable to accept that a fasciocutaneous flap has a 15% to 20% increased
      survival over comparable cutaneous flaps. METHODS: The distal-based posterior
      tibial fasciocutaneous flap was designed and successfully transferred clinically
      to cover lower leg and foot defects in four patients. RESULTS: No complications,
      including distal ischemia, infection, and failure, in flaps were seen. Although
      donor site of fasciocutaneous flaps is significant and can often be justified, it
      is not as significant as the donor area of the free flaps. CONCLUSIONS: The
      versatility, advantages, and disadvantages of this new flap in the reconstruction
      of defects of the lower leg and foot are discussed.

PMID- 18332824
TI  - The comparison of characteristic and clinical features of self-inflicted
      abdominal stab wound patients in Japan: simple stab wounds versus Hara-kiri
      wounds.
AB  - BACKGROUND: The proportion of suicide attempts by infliction of abdominal stab
      wounds (ASWs) is higher in Japan than in other counties. There are few clinical
      reports on these wounds, especially hara-kiri wounds, which involve transversely
      cutting the abdomen. This study aimed to investigate Japanese patients with self
      inflicted hara-kiri wounds and determine their characteristics and clinical
      features. METHODS: We investigated 84 patients with self-inflicted ASWs who had
      been transferred to our hospital between April 1994 and March 2004. We recorded
      their characteristics and clinical features. They were then divided into two
      groups depending on their wound type, namely, simple stab wounds (SSWs) and hara
      kiri wounds. The characteristics and clinical features of each group were then
      compared. RESULTS: SSWs were frequently observed in the periumbilical and
      epigastric regions, whereas most hara-kiri wounds were observed in the middle
      abdomen. The rate of organ injury was 58.7% (44 of 75) for SSWs and 66.7% (6 of
      9) for hara-kiri wounds; no significant difference was observed in this regard.
      SSWs resulted in injury to various organs, whereas hara-kiri wounds typically
      caused small bowel, mesenterium, omentum, and major vascular injuries. Small
      bowel and major vascular injuries had a significantly high incidence in hara-kiri
      wounds. The mortality rate caused by hara-kiri wounds was significantly higher
      than that caused by SSWs (1.3% vs. 22.2%). CONCLUSION: The mortality rate caused
      by ASWs is relatively low. However, hara-kiri wounds might be a risk factor for
      death. Further, because hara-kiri wounds transversely cut the abdomen, they might
      be a risk factor for major vascular injury.

PMID- 18332825
TI  - Long-term functional outcome of penetrating sciatic nerve injury.
AB  - BACKGROUND: Penetrating sciatic nerve injuries resulting from gunshot wounds
      (GSW) or blast injuries are rare. The role of operative treatment of these
      injuries remains obscure, and to date, specific outcome measures after this type
      of injury are still missing. METHODS: We retrospectively studied 29 patients with
      penetrating sciatic nerve injuries mostly resulting from GSW or blast, during the
      years 1990 to 2002, and compared those who where treated operatively versus
      nonoperatively, with minimal follow-up period of 2 years. Fourteen patients were
      operated and 15 treated nonoperatively. RESULTS: Functional outcomes included
      neurologic recovery (Clawson and LSUHSC) and functional outcome (Brooks & Healey
      score, SF-36) scores. The functional neurologic recovery of the peroneal division
      of the sciatic nerve when compared with the tibial division was worse in both
      groups. No significant differences were found among the two groups in the rate of
      neurologic recovery, use of walking aids, and SF-36 scores. However, there was a
      tendency for lesser pain and better walking ability among the operated group.
      Seven patients who sustained blast injury had no neurologic recovery of the
      peroneal division of the nerve. These also had multiple injury sites in the
      involved sciatic nerve. CONCLUSION: High-energy injury to the sciatic nerve,
      although devastating, can result in a reasonable long-term functional level.

PMID- 18332826
TI  - Replantation of total avulsed scalp with microsurgery: experience of eight cases
      and literature review.
AB  - BACKGROUND: Reports in the literature about scalp replantation are mostly
      sporadic; rarely can one find a large series. We present our experience with
      eight cases of scalp amputation replanted microsurgically. METHODS: From 1992 to
      2003, eight patients who sustained scalp amputation injuries underwent
      microsurgical replantation. Age ranged from 3 to 46 years (average, 27.3), and
      four patients were male. The scalp amputations in the three adult male patients
      were sustained from cutting incidents by a blade, whereas those in the four
      female patients were from their long hair getting caught in a roller machine. A 3
      year-old boy suffered scalp avulsion from a dog bite. A vein graft was needed in
      four patients whose scalp injuries resulted either from avulsion or a dog bite,
      which was not deemed necessary for those sustained by cutting injuries. RESULTS:
      Seven of the eight replantations were successful. The failed replantation in this
      series was the case where only arterial revascularization was performed, which
      resulted in venous congestion. Rotation scalp flap was placed to cover the
      defect. A boy who sustained scalp amputation from a dog bite suffered partial
      necrosis of the replanted scalp, which was covered with a skin graft. The
      resulting alopecia area was eventually excised after tissue expansion.
      CONCLUSION: Successful replantations can achieve the best esthetic and functional
      results compared with other procedures. Scalp amputations sustained from sharp
      cuts seem to be quite as common as hair traction injuries. Such amputation
      injuries were more common in male patients with short hair. The manner of injury
      often will influence planning during replantation. Even if the amputated scalp
      was crushed or contaminated, such as those sustained from animal bites,
      replantation should still proceed, unless a greater contraindication exists.

PMID- 18332827
TI  - Effects of poly-N-acetyl glucosamine (pGlcNAc) patch on wound healing in db/db
      mouse.
AB  - BACKGROUND: Poly-N-acetyl glucosamine (pGlcNAc) nanofiber-based materials,
      produced by a marine microalga, have been characterized as effective hemostatic
      agents. In this study, we hypothesized that a pGlcNAc fiber patch may enhance
      wound healing in the db/db mouse. METHODS: pGlcNAc patches were applied on 1-cm,
      full-thickness, skin wounds in the db/db mouse model. Wounds (n = 15 per group)
      were dressed with a pGlcNAc nanofiber patch for 1 hour, 24 hours, or left
      untreated. After the application time, patches were removed and wounds were
      allowed to heal spontaneously. The rate of wound closure was evaluated by digital
      analysis of unclosed wound area as a function of time. At day 10, wounds (n = 7
      per group) were harvested and quantified with immunohistochemical markers of
      proliferation (Ki-67) and vascularization (platelet endothelial cell adhesion
      molecule). RESULTS: Wounds dressed with pGlcNAc patches for 1 hour closed faster
      than control wounds, reaching 90% closure in 16.6 days, 9 days faster than
      untreated wounds. Granulation tissue showed higher levels of proliferation and
      vascularization after 1-hour treatment than the 24-hour and left-untreated
      groups. Foreign body reaction to the material was not noted in applications up to
      24 hours. DISCUSSION: In addition to its hemostatic properties, the pGlcNAc
      material also appears to accelerate wound closure in healing-impaired genetically
      diabetic mice. This material, with its combination of hemostatic and wound
      healing properties, has the potential to be effective agent for the treatment of
      complicated wounds.

PMID- 18332828
TI  - A basic fibroblast growth factor improves lower extremity wound healing with a
      porcine-derived skin substitute.
AB  - BACKGROUND: Although a number of cytokine or growth factor therapies for wound
      acceleration have been reported, few mentioned the quality of the outcome. The
      lower extremity is important in esthetics as well as in function, because it is
      exposed. Recently, a growth factor, namely basic growth factor (bFGF) is widely
      used for difficult wound healing with a porcine-derived bilayered artificial
      dermis for better wound closure. Thus, their combination use was tested
      clinically. METHODS: Sequential lower extremity reconstruction by an artificial
      dermis with or without bFGF administration and secondary split-thickness skin
      grafting was measured for hardness using a durometer, and the moisture parameters
      assessed such as effective contact coefficient, transepidermal water loss (TEWL),
      water content and thickness using a moisture meter for at least 6 months after
      the final procedure and compared with normal skin control. RESULTS: There was
      significantly less skin hardness using a durometer in bFGF treatment compared
      with non-bFGF treatment (16.2 +/- 3.83 vs. 29.2 +/- 4.94, p < 0.01). Effective
      contact coefficient, TEWL, water content, and thickness in non-bFGF treatment
      were all significantly greater than those in bFGF treatment, whereas water
      content and thickness in bFGF treatment were comparable with those of the
      control. CONCLUSION: The use of bFGF as artificial dermis for extensive and
      deeper tissue loss coverage demonstrated better reconstruction quality in terms
      of hardness using a durometer and the function of the stratum corneum by moisture
      analysis.

PMID- 18332829
TI  - Early use of allograft skin: are 3-day microbiologic cultures safe?
AB  - BACKGROUND: Under the guidance of the American Association of Tissue Banks and
      the Food and Drug Administration, the use of allograft skin is safer than ever.
      In addition to the donor selection process and serology studies, current practice
      is to wait until 7 days of negative microbiologic cultures are completed before
      use. However, we have used 3 days of negative cultures in special cases as needed
      for clinical use. But how safe is this practice? METHODS: Between 2002 and 2003,
      735 allograft skin donors were authorized for exceptional release. Exceptional
      release forms were signed by surgeons to document knowledge of the 3-day
      microbiologic cultures. RESULTS: Only three donors were recalled for positive
      cultures. The recall rate was 0.41%. CONCLUSIONS: The use of 3-day microbiologic
      cultures is 99.59% safe. Thus, the early use of allograft skin does not increase
      the chances of microbiologic contamination to patients.

PMID- 18332830
TI  - Pediatric trauma rehabilitation: a value-added safety net.
AB  - This article reviews the literature on the effectiveness of rehabilitation after
      pediatric trauma. The characteristics of comprehensive pediatric trauma
      rehabilitation services during the initial acute care hospitalization, as well as
      subsequent inpatient and outpatient care during the first 12 months after injury
      are discussed. Important research questions and the challenges associated with
      conducting such research are identified. For many children, rehabilitation is the
      final common pathway that may define the success or failure of their treatment
      their ultimate outcome. Large, prospective, multicenter studies will be needed so
      that seriously injured children can receive standardized and effective
      rehabilitative care.

PMID- 18332831
TI  - Seat belt trauma: pectoralis muscle rupture and delayed mesh repair.
AB  - To our knowledge, this is the first reported case of a seat belt-related rupture
      of the pectoralis major muscle and its successful delayed repair using mesh. We
      report a case of a 34-year-old white man who sustained a right pectoralis major
      muscle rupture from a seat belt during a motor vehicle crash. The patient
      presented to us 2 years after the injury. We introduce a technique using mesh
      that results in a successful repair of a cosmetically disfiguring chest wall
      defect.

PMID- 18332832
TI  - Percutaneous reduction of a displaced femoral intercondylar fracture assisted
      with arthroscopy and fluoroscopy.

PMID- 18332833
TI  - Thiopental-associated dyskalemia in severe head trauma.

PMID- 18332834
TI  - Vagal nerve transection after gunshot wound to neck.

PMID- 18332835
TI  - Jugular venous air after basilar skull fracture.

PMID- 18332837
TI  - Progressive supranuclear palsy: a current review.
AB  - BACKGROUND: Progressive supranuclear palsy (PSP) is the second most common cause
      of parkinsonism after Parkinson's disease (PD). The classic syndrome of PSP is
      widely recognized by neurologists as a combination of down gaze palsy with
      progressive rigidity and imbalance leading to falls. At the same time, few
      clinicians are proficient at treating PSP and recognizing the nonclassic
      presentations of this debilitating disorder often resulting in delays in
      diagnosis and misguided treatment. REVIEW SUMMARY: Over the last decade many
      lines of investigation have helped refine PSP at the clinical, neuroimaging,
      pharmacologic and molecular levels. It is the purpose of this literature review
      to help clinicians identify PSP earlier in its course, to better understand its
      pathophysiology, and to provide a more focused, symptom-based treatment approach.
      Eighty-two peer-reviewed articles on the topic of PSP and other neurodegenerative
      disorders have been reviewed. CONCLUSION: It is clear that PSP continues to be an
      under-recognized disorder with multilevel involvement of the neuraxis that helps
      differentiate it from other akinetic rigid syndromes such as PD. A greater
      appreciation of its atypical presentations, more attention to its neurobehavioral
      signs and better imaging techniques are some of the advances that will help
      facilitate earlier detection, which may reduce morbidity by helping anticipate
      early falls and minimizing unnecessary diagnostic procedures. Surgical approaches
      to PSP have been ineffective so far. Carefully targeted symptomatic treatment
      with drugs and other therapies is available and effective at reducing morbidity
      and improving quality of life.

PMID- 18332838
TI  - Impulse control disorders and pathological gambling in patients with Parkinson
      disease.
AB  - OBJECTIVES: The primary aim of this article is to critically review the clinical
      features and comorbidities, epidemiology, pathophysiology, and treatment of
      impulse control disorder (ICD) associated with Parkinson disease (PD). METHODS:
      References for this review were identified by searches of PubMed from 1980 until
      January 2008 with the terms "Parkinson disease," "impulse control," "pathologic
      gambling,""hypersexuality," "levodopa," and "dopamine agonists." Articles were
      also identified through searches of the authors' own files. Only papers published
      in English were reviewed. RESULTS: Pathologic gambling has emerged as one of the
      most prominent ICDs, although hypersexuality, compulsive shopping and other
      manifestations of obsessive-compulsive disorder may also dominate PD-related
      behavioral manifestations. Affected patients may demonstrate a pattern of self
      escalation of dopaminergic medication dosing which may lead to a state of
      dependency. CONCLUSIONS: Patients most commonly affected by ICD, such as
      pathologic gambling and hypersexuality, are males who develop PD at a younger
      age, and those with a previous history of mood disorder, alcohol abuse, or
      obsessive-compulsive disorder. Dopaminergic drugs, particularly dopamine
      agonists, play an important role in triggering these nonmotor symptoms.

PMID- 18332839
TI  - Frontal-subcortical dementias.
AB  - Frontal-subcortical dementias are a heterogeneous group of disorders that share
      primary pathology in subcortical structure and a characteristic pattern of
      neuropsychologic impairment. Their clinical presentation is characterized by
      memory disorders, an impaired ability to manipulate acquired knowledge, important
      changes of personality (apathy, inertia, or depression), and slowed thought
      processes (or bradyphrenia). It also has marked frontal dysfunction. Classic
      frontal-subcortical dementias include Huntington chorea, Parkinson disease
      dementia, progressive supranuclear palsy, thalamic degeneration, subcortical
      vascular dementia, multiple sclerosis, the acquired immunodeficiency syndrome
      dementia complex, depressive pseudodementia, and some other rare dementias like
      spinocerebellar degenerative syndromes, Hallervorden-Spatz disease,
      choreoacanthocytosis, idiopathic basal ganglia calcification, Guamanian
      parkinsonism-dementia complex, corticobasal degeneration multiple system atrophy,
      Wilson disease, metachromatic leukodystrophy, adrenoleukodystrophy,
      hypoparathyroidism, sarcoidosis, and other CNS inflammatory disorders. Anatomic
      data suggest that the frontal signs result from a disconnection of the frontal
      cortex from the basal ganglia. However, most frontal-subcortical dementias show
      cortical atrophy in later stages, and cortical dementias have subcortical
      pathology at some point. In fact, the concept might be seen as a continuum, and
      only the 2 extremes would be represented by pure cortical or subcortical
      pathology. Anyway, subcortical disorders may still be more similar to one another
      than they are to AD. Possibly, frontal-subcortical and cortical dementias are the
      description of the prior main target of the disease process, ending up in both
      cases in a global dementia. Although the dichotomy cortical versus frontal
      subcortical dementia is not strict, the 2 concepts still seem to have advantages.

PMID- 18332840
TI  - Headache and pregnancy.
AB  - BACKGROUND: Many women who suffer from migraine and tension-type headaches (TTHs)
      have an improvement in the frequency of these headaches during pregnancy. At the
      same time pregnancy predisposes women to a number of potentially life-threatening
      conditions which can present with headache. Accurate diagnosis and treatment of
      headache during pregnancy is essential. REVIEW SUMMARY: The primary objectives of
      this review are to: (1) Summarize the natural history of primary headache
      disorders, including migraine, tension-type, and cluster headaches during
      pregnancy, as well as the impact of migraine on pregnancy outcomes and
      complications.(2) Summarize the therapeutic options and strategies for managing
      headaches in pregnancy and (3) Discuss the causes of secondary headaches and the
      diagnostic evaluation for new onset headache during pregnancy. CONCLUSION:
      Primary headache disorders, in particular TTHs and migraines, generally improve
      during pregnancy. However the frequency of improvement varies greatly. Because
      the pathophysiology of both migraines and TTHs is poorly understood, this limits
      our ability to predict improvement. Future research should be focused on headache
      pathophysiology and the effect of ovarian hormones and the pregnant state on
      headache pathogenesis.

PMID- 18332841
TI  - Remission of refractory neurosarcoidosis treated with brain radiotherapy: a case
      report and a literature review.
AB  - Sarcoidosis is a chronic disease of unknown etiology characterized by the
      presence of T lymphocytes, mononuclear phagocytes, and noncaseating epithelioid
      granulomas in the tissues. Central nervous system involvement occurs in about 5%
      of the cases. The chronic form of neurosarcoidosis is particularly resistant to
      medical treatments. No universally accepted therapeutic protocols are currently
      available. Corticosteroids are the first line of therapy, but other
      immunosuppressive treatments are frequently added to the patient's regimen,
      although this strategy is not adequately supported by controlled clinical trials.
      For patients resistant to or not tolerating multiple alternate immunotherapeutic
      drugs, some authors suggest central nervous system radiotherapy. We present a
      case of a patient with neurosarcoidosis involving the hypothalamo-hypophyseal
      region and causing panhypopituitarism who had a poor response to and experienced
      severe side effects from conventional immunosuppressive treatments. The patient
      experienced a good clinical response to cranial irradiation. We review the
      literature on this subject.

PMID- 18332842
TI  - An unusual cause of cardioembolic stroke: isolated left ventricular
      noncompaction.
AB  - BACKGROUND: Isolated left ventricular noncompaction (ILVNC) is a rare congenital
      condition that is the result of an intrauterine developmental arrest, which stops
      the compaction of the loose myocardial fiber meshwork of the left ventricle. This
      condition is recognized by an excessively prominent trabecular meshwork and deep
      intertrabecular recesses of the left ventricle. Although these intertrabecular
      recesses are prone to thrombus formation, with resulting embolic sequelae, the
      literature describes only 1 adult case of a stroke caused by ILVNC. CASE REPORT:
      We describe a case of cerebral cardioembolism in a 33-year-old man due to ILVNC.
      Because of echocardiography (ECHO) findings in this case, cardiac magnetic
      resonance imaging (cMRI) was performed, which allowed a definite diagnosis to be
      obtained. CONCLUSION: This case should highlight the importance of performing
      cMRI especially in younger patients with embolic stroke, if the ECHO suggests a
      suspected myocardial disorder.

PMID- 18332843
TI  - Embolic stroke secondary to cardiac papillary fibroelastoma.
AB  - INTRODUCTION: Papillary fibroelastoma is the most common primary cardiac valvular
      tumor. Historically, papillary fibroelastoma was an incidental autopsy finding,
      deemed to have no clinical significance. More recently, reports of symptomatic
      cases of papillary fibroelastoma with complications such as myocardial infarction
      and stroke suggest it should be considered a potentially dangerous lesion. In
      this report, we describe the clinical and echocardiographic findings of 3
      patients with cardiac papillary fibroelastoma who presented with cerebral
      vascular events. OBJECTIVE: To describe the clinical and echocardiographic
      findings of 3 patients with cardiac papillary fibroelastoma (CPF) who presented
      cerebral vascular events. METHODS: Describe the findings of 3 patients and review
      of the literature. RESULTS: We report 3 cases with cerebral ischemic events
      associated with the presence of CPF that were confirmed by histopathological
      examination. CONCLUSIONS: Cardiogenic embolism is recognized increasingly as an
      important cause of stroke, accounting of 20% of ischemic strokes. Cardioembolic
      stroke is largely preventable. The likelihood of recurrence is relatively high
      for most cardioembolic sources and therefore secondary stroke prevention is
      fundamental. TEE allowed to characterize well-established sources of embolism,
      and it was the best diagnostic approach in our patients. Magnetic resonance
      imaging was used in 1 of these patients, while it confirmed the presumptive
      diagnosis of cardiac tumor. The first-choice treatment of symptomatic CPF is
      surgical excision which must be performed as early as possible to reduce the risk
      of early recurrences of embolic events. The use of TEE in the evaluation of
      cerebral vascular events is not routinely performed, this method must be
      considered in patients for whom the cause of cerebrovascular ischemia is unclear,
      after noninvasive neurovascular studies.

PMID- 18332844
TI  - Left atrial sarcoma presenting as cerebral infarction.
AB  - OBJECTIVE: Primary heart tumors are rare and most of them are benign. The
      majority of benign cardiac tumors are myxomas, although almost all malignant
      cardiac tumors are sarcomas. Malignant cardiac tumors usually appear in children.
      METHODS: There have been cases described of stroke secondary to embolism caused
      by cardiac sarcomas, but it is rarely the first manifestation of the tumor.
      RESULTS: We describe a 48-year-old man who suffered a cardioembolic stroke
      secondary to cardiac sarcoma. CONCLUSION: Malignant cardiac tumors typically
      appear through 1 of 4 mechanisms: obstruction to blood flow and interference with
      valve function; local invasion causing arrhythmias or pericardial effusion;
      embolic phenomena or systemic symptoms. We analyze the characteristics of cardiac
      sarcoma and the pathophysiology of embolism.

PMID- 18332845
TI  - Adjunctive haloperidol prophylaxis reduces postoperative delirium severity and
      duration in at-risk elderly patients.
AB  - BACKGROUND: Delirium is a potentially life-threatening syndrome that is
      particularly common in elderly hospitalized patients, especially those with
      preexisting neurologic disorders. Nonpharmacological tactics can reduce the
      incidence and severity of delirium in acute care settings and antipsychotic drugs
      are widely used to treat established delirium. More effective preventive
      strategies could notably impact morbidity, mortality, and health care costs.
      OBJECTIVE: To determine whether antipsychotic drug prophylaxis reduces the
      incidence and severity of postoperative delirium in at-risk elderly patients.
      METHODS: We addressed the objective through development of a structured
      critically appraised topic that included a clinical scenario, structured
      question, search strategy, critical appraisal, results, evidence summary,
      commentary, and conclusions. Participants included consultant and resident
      neurologists, a medical librarian, clinical epidemiologists, and content experts
      in the field of cognitive disorders. RESULTS: One randomized controlled trial
      addressed the question. In at-risk patients aged >70 years, oral haloperidol 0.5
      mg TID, administered from up to 72 hours preoperatively until the third
      postoperative day, did not alter the incidence of postoperative delirium (15.1%)
      compared with placebo (16.5%; relative risk 0.91; 95% confidence interval 0.59
      1.44). However, the study was underpowered for this primary outcome, possibly
      because both groups received nonpharmacological delirium prevention strategies.
      Haloperidol significantly reduced delirium severity ratings, delirium duration
      (from a mean of 11.8 to 5.4 days), and length of hospital stay in affected
      participants (from 22.6 to 17.1 day). CONCLUSION: Adjunctive low-dose haloperidol
      prophylaxis reduces delirium severity, duration, and subsequent hospitalization
      length in elderly at-risk patients. Further study is needed to determine the
      optimal pharmacological approach, combination with nonpharmacological strategies,
      and generalizability to other settings.

PMID- 18332846
TI  - 10 questions on central nervous system vasculitis.

PMID- 18332847
TI  - Patient and family fact sheet. Chronic inflammatory demyelinating polyneuropathy.

PMID- 18332848
TI  - Hotly debated topics in obstetric anesthesiology 2008: a theory of relativity.
AB  - This paper reviews and discusses three controversial subjects regarding treatment
      of intraoperative nausea and other complications experienced by patients
      undergoing cesarean delivery under spinal anesthesia: (1) the administration of
      supplemental oxygen, (2) prophylactic vasopressors and (3) the use of low-dose
      combined spinal epidural anesthesia (CSE). While not universally acknowledged,
      recent data suggest that the routine administration of supplemental oxygen to
      normal-weight, healthy patients undergoing elective cesarean delivery is
      unnecessary, especially when spinal hypotension is minimized. Supplemental oxygen
      administration does not prevent intraoperative or postoperative nausea and
      vomiting. Additionally, although higher inspired oxygen fractions modestly
      increase fetal oxygenation, they also cause a concomitant increase in oxygen free
      radical activity in both mother and fetus, which may weaken the infant's ability
      to withstand subsequent neonatal insult. The use of prophylactic vasopressor
      infusions may benefit some patients, but parenteral preanesthetic ephedrine
      administration is not warranted. Heart rate variability guided therapy could help
      identify patients at risk for developing severe hypotension after spinal
      anesthesia. High-dose phenylephrine infusion in conjunction with rapid co
      hydration is efficient, but is unfortunately associated with a relatively high
      incidence of maternal bradycardia. Oxygen, fluid administration and prophylactic
      vasopressors may not be the solution to hypotension, nausea and vomiting
      associated with spinal anesthesia during cesarean delivery. Lower dose spinal
      anesthesia as part of a CSE technique reduces the incidence of maternal
      hypotension, and in our opinion is the best option currently available.

PMID- 18332849
TI  - Overview on the use of recombinant human thyrotropin in thyroid cancer of
      follicular cell origin.
AB  - Stimulation by recombinant human thyroid-stimulating hormone (rhTSH) has gained
      wide acceptance as an alternative to thyroid hormone withdrawal in the management
      of patients with differentiated thyroid cancer. RhTSH has the advantage to avoid
      both the clinical consequences of hypothyroidism, with a positive impact on
      quality of life and work productivity, and the risk of cancer growth due to the
      long-lasting endogenous thyrotropin stimulation. RhTSH is a heterodimeric
      glycoprotein produced by recombinant DNA technology that has the ability to
      stimulate thyroglobulin production and radioiodine uptake by thyroid cells. RhTSH
      is now widely used in the follow-up of thyroid cancer patients in order to
      improve sensitivity of thyroglobulin (Tg) measurement as well as in preparation
      of (131)I diagnostic whole-body scan. Although initially approved only for
      diagnostic purposes, rhTSH has been now approved both in Europe and in the United
      States for remnant ablation in low-risk patients. As far as residual or
      metastatic cancer treatment, rhTSH has been initially used on a compassionate
      need basis for elderly and frailer patients and for patients in whom the
      withdrawal of thyroid hormone was medically contraindicated. Nowadays, there is a
      trend for widening the use of rhTSH in therapy, in order to avoid hypothyroidism
      and the concern about the effect of prolonged endogenous thyroid-stimulating
      hormone stimulation on cancerous cells. Unfortunately, the studies which address
      the efficacy of rhTSH in cancer treatment are still scarce and the opportunity of
      its clinical application remains controversial. In addition, rhTSH has been shown
      to improve the accuracy of [(18)F]-2-fluoro-deoxy-D-glucose positron emission
      tomography to detect non-functioning thyroid cancer. Although all studies agree
      on that rhTSH is much better tolerated from the clinical point of view than
      thyroid hormone withdrawal, there is some controversy about its comparative
      ability to raise Tg levels and concentrate radioiodine in cancerous thyroid
      cells. The aim of this paper is to review the performances of rhTSH as compared
      to hypothyroidism, considering Tg stimulation and diagnostic whole-body scan
      sensitivity during follow-up, and its effectiveness for normal remnant ablation
      and for therapy of metastatic disease.

PMID- 18332850
TI  - K(ATP) channel expression and pharmacological in vivo and in vitro studies of the
      K(ATP) channel blocker PNU-37883A in rat middle meningeal arteries.
AB  - BACKGROUND AND PURPOSE: Dilatation of cerebral and dural arteries causes a
      throbbing, migraine-like pain, indicating that these structures are involved in
      migraine. Clinical trials suggest that adenosine 5'-triphosphate-sensitive K(+)
      (K(ATP)) channel opening may cause migraine by dilatating intracranial arteries,
      including the middle meningeal artery (MMA). We studied the K(ATP) channel
      expression profile in rat MMA and examined the potential inhibitory effects of
      the K(ATP) channel blocker PNU-37883A on K(ATP) channel opener-induced relaxation
      of the rat MMA, using the three K(ATP) channel openers levcromakalim, pinacidil
      and P-1075. EXPERIMENTAL APPROACH: mRNA and protein expression of K(ATP) channel
      subunits in the rat MMA were studied by quantitative real-time PCR and western
      blotting, respectively. The in vivo and in vitro effects of the K(ATP) channel
      drugs on rat MMA were studied in the genuine closed cranial window model and in
      myograph baths, respectively. KEY RESULTS: Expression studies indicate that
      inwardly rectifying K(+) (Kir)6.1/sulphonylurea receptor (SUR)2B is the major
      K(ATP) channel complex in rat MMA. PNU-37883A (0.5 mg kg(-1)) significantly
      inhibited the in vivo dilatory effect of levcromakalim (0.025 mg kg(-1)),
      pinacidil (0.38 mg kg(-1)) and P-1075 (0.016 mg kg(-1)) in rat MMA. In vitro PNU
      37883A significantly inhibited the dilatory responses of the three K(ATP) channel
      openers in rat MMA at 10(-7) and 3 x 10(-7) M. CONCLUSIONS AND IMPLICATIONS: We
      suggest that Kir6.1/SUR2B is the major functional K(ATP) channel complex in the
      rat MMA. Furthermore, we demonstrate the potent in vivo and in vitro blocking
      potentials of PNU-37883A on K(ATP) channel opener-induced relaxation of the rat
      MMA.

PMID- 18332851
TI  - Activation of prostaglandin EP receptors by lubiprostone in rat and human stomach
      and colon.
AB  - BACKGROUND AND PURPOSE: Lubiprostone (Amitiza), a possible ClC-2 channel opener
      derived from prostaglandin E(1) and indicated for the treatment of constipation,
      increases chloride ion transport and fluid secretion into the intestinal lumen.
      As lubiprostone may also directly modulate gastrointestinal motility, we
      investigated its actions and the possible involvement of prostaglandin EP
      receptor activation on rat and human isolated gastrointestinal preparations.
      EXPERIMENTAL APPROACH: Rat and human isolated preparations were mounted in tissue
      baths for isometric recording. The effects of lubiprostone on muscle tension and
      on electrically stimulated, neuronal contractions were investigated in the
      absence and presence of EP receptor antagonists. KEY RESULTS: In rat and human
      stomach longitudinal muscle, lubiprostone induced a contraction (pEC(50) of 7.0+/
      0.0, n=4 and 6.4+/-0.2, n=3, respectively), which was inhibited by pretreatment
      with the EP(1) receptor antagonist, EP(1)A 300 nM (pEC(50) reduced to 6.2+/-0.2,
      n=6), but not by the EP(3) or EP(4) receptor antagonists (L-798106 and GW627368X,
      respectively, 1 microM, P>0.05). Lubiprostone also reduced electrically
      stimulated, neuronal contractions in rat and human colon circular muscle
      preparations (pIC(50) of 8.9+/-0.4, n=7 and 8.7+/-0.9, n=6, respectively), an
      effect mediated pre-junctionally. This effect was reduced by the EP(4) receptor
      antagonist (pIC(50) of 6.7+/-1.1, n=7 and 7.7+/-0.4, n=6, respectively) but not
      by EP(1) or EP(3) receptor antagonists. CONCLUSIONS AND IMPLICATIONS: In rats and
      humans, lubiprostone contracts stomach longitudinal muscle and inhibits
      neuronally mediated contractions of colon circular muscle. Experiments are now
      needed to determine if this additional activity of lubiprostone contributes to
      its clinical efficacy and/or side-effect profile.

PMID- 18332852
TI  - Na(+)/Ca(2+) exchanger inhibition exerts a positive inotropic effect in the rat
      heart, but fails to influence the contractility of the rabbit heart.
AB  - BACKGROUND AND PURPOSE: The Na(+)/Ca(2+) exchanger (NCX) may play a key role in
      myocardial contractility. The operation of the NCX is affected by the action
      potential (AP) configuration and the intracellular Na(+) concentration. This
      study examined the effect of selective NCX inhibition by 0.1, 0.3 and 1.0 microM
      SEA0400 on the myocardial contractility in the setting of different AP
      configurations and different intracellular Na(+) concentrations in rabbit and rat
      hearts. EXPERIMENTAL APPROACH: The concentration-dependent effects of SEA0400 on
      I(Na/Ca) were studied in rat and rabbit ventricular cardiomyocytes using a patch
      clamp technique. Starling curves were constructed for isolated, Langendorff
      perfused rat and rabbit hearts. The cardiac sarcolemmal NCX protein densities of
      both species were compared by immunohistochemistry. KEY RESULTS: SEA0400
      inhibited I(Na/Ca) with similar efficacy in the two species; there was no
      difference between the inhibitions of the forward or reverse mode of the NCX in
      either species. SEA0400 increased the systolic and the developed pressure in the
      rat heart in a concentration-dependent manner, for example, 1.0 microM SEA0400
      increased the maximum systolic pressures by 12% relative to the control, whereas
      it failed to alter the contractility in the rabbit heart. No interspecies
      difference was found in the cardiac sarcolemmal NCX protein densities.
      CONCLUSIONS AND IMPLICATIONS: NCX inhibition exerted a positive inotropic effect
      in the rat heart, but it did not influence the contractility of the rabbit heart.
      This implies that the AP configuration and the intracellular Na(+) concentration
      may play an important role in the contractility response to NCX inhibition.

PMID- 18332853
TI  - Photodynamic activity of BAM-SiPc, an unsymmetrical bisamino silicon(IV)
      phthalocyanine, in tumour-bearing nude mice.
AB  - BACKGROUND AND PURPOSE: Ever since the discovery of photodynamic therapy, there
      has been a continuous search for more potent photosensitizers. Towards that end,
      we have synthesized a number of novel phthalocyanine derivatives. The
      unsymmetrical bisamino silicon(IV) phthalocyanine BAM-SiPc is one of the most
      potent compounds. In in vitro cell culture, it exhibits high phototoxicity
      against a number of cancer cell lines. EXPERIMENTAL APPROACH: In the present
      investigation, the in vivo effect of BAM-SiPc was studied in the tumour-bearing
      nude mice model. The biodistribution of BAM-SiPc was followed to evaluate its
      tumour selectivity and rate of clearance. The tumour volume in the
      hepatocarcinoma HepG2- and the colorectal adenocarcinoma HT29-bearing nude mice
      was measured after photodynamic therapy. The level of intrinsic toxicity induced
      was also investigated. Finally, the metabolism of BAM-SiPc in the 'normal' WRL68
      liver cells and the hepatocarcinoma HepG2 cells was compared. KEY RESULTS: The
      results not only showed significant tumour regression of HepG2 and growth
      inhibition of HT29 in the tumour-bearing nude mice, but also no apparent hepatic
      or cardiac injury with the protocol used. Histological analyses showed that
      apoptosis was induced in the solid tumour. BAM-SiPc could be metabolized by WRL68
      liver cells but not by the hepatocarcinoma HepG2 cells. Unfortunately, BAM-SiPc
      did not show any specific targeting towards the tumour tissue. CONCLUSIONS AND
      IMPLICATIONS: The efficiency of BAM-SiPc in inhibiting tumour growth makes it a
      good candidate for further evaluation. Enhancement of its uptake in tumour tissue
      by conjugation with biomolecules is currently under investigation.

PMID- 18332854
TI  - Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and
      in vivo.
AB  - BACKGROUND AND PURPOSE: The clinical use of arsenic trioxide (As(2)O(3)), a
      potent antineoplastic agent, is limited by its severe cardiotoxic effects. QT
      interval prolongation and apoptosis have been implicated in the cardiotoxicity of
      As(2)O(3). The present study was designed to evaluate the effects of resveratrol
      on As(2)O(3)-induced apoptosis and cardiac injury. EXPERIMENTAL APPROACH: In a
      mouse model of As(2)O(3)-induced cardiomyopathy in vivo, QT intervals and plasma
      enzyme activities were measured; cardiac tissues were examined histologically and
      apoptosis assessed. In H9c2 cardiomyocyte cells, viability, apoptosis, generation
      of reactive oxygen species (ROS) and cellular calcium levels were measured. KEY
      RESULTS: In the mouse model, resveratrol reduced As(2)O(3)-induced QT interval
      prolongation and cardiomyocyte injury (apoptosis, myofibrillar loss and
      vacuolization). In addition, increased lactate dehydrogenase activity and
      decreased activities of glutathione peroxidase, catalase and superoxide dismutase
      were observed in the plasma of As(2)O(3)-treated mice; these changes were
      prevented by pretreatment with resveratrol. In As(2)O(3)-treated H9c2
      cardiomyocytes, resveratrol significantly increased cardiomyocyte viability and
      attenuated cell apoptosis as measured by acridine orange/ethidium bromide
      staining, TdT-mediated dUTP nick end labelling assay and caspase-3 activity.
      As(2)O(3)-induced generation of ROS and intracellular calcium mobilization in
      H9c2 cells was also suppressed by pretreatment with resveratrol. CONCLUSIONS AND
      IMPLICATIONS: Our results showed that resveratrol significantly attenuated
      As(2)O(3)-induced QT prolongation, structural abnormalities and oxidative damage
      in the heart. In H9c2 cardiomyocytes, resveratrol also decreased apoptosis,
      production of ROS and intracellular calcium mobilization induced by treatment
      with As(2)O(3). These observations suggested that resveratrol has the potential
      to protect against cardiotoxicity in As(2)O(3)-exposed patients.

PMID- 18332855
TI  - Serotonin decreases HIV-1 replication in primary cultures of human macrophages
      through 5-HT(1A) receptors.
AB  - BACKGROUND AND PURPOSE: 5-HT (serotonin) is known to be involved in
      neuroinflammation and immunoregulation. The human immunodeficiency virus (HIV)
      targets cells such as monocytes/macrophages, which colocalize with 5-HT-releasing
      cell types, mostly platelets. In this study, we investigated the effects of 5-HT
      on HIV-1-infected macrophages in vitro. EXPERIMENTAL APPROACH: Human macrophages
      cultured in serum-free medium were treated over 7 days with 5-HT at three
      concentrations (0.01, 1 and 100 microM) with or without agonists and antagonists
      of 5-HT(1A) and 5-HT(2) receptors. After 7 days of treatment, macrophages were
      infected with HIV-1/Ba-L and virus replication was monitored over 16 days and
      expression of proviral HIV DNA was investigated by PCR after 24 h of infection.
      Cell surface expression of HIV-1/Ba-L receptor (CD4) and coreceptor (CCR5) was
      investigated by flow cytometry. The CCR5 ligand, macrophage inflammatory protein
      1alpha (MIP-1alpha), was quantified by ELISA in cell culture supernatants and MIP
      1alpha mRNA expression was assessed by reverse transcriptase-PCR. KEY RESULTS: In
      vitro, 5-HT downregulated the membranous expression of CCR5 and led to a decrease
      of HIV-1 infection, probably through its action on 5-HT(1A) receptors. 5-HT (100
      microM) was also able to induce overexpression of MIP-1alpha mRNA leading to an
      increase of MIP-1alpha secretion by human macrophages. CONCLUSIONS AND
      IMPLICATIONS: The effects of 5-HT on HIV infection could be a consequence of the
      increase in MIP-1alpha concentrations and/or CCR5 receptor downregulation. These
      results suggest that 5-HT can inhibit the replication of HIV-1 in primary culture
      of human macrophages through its action on 5-HT(1A) receptors.

PMID- 18332856
TI  - Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of
      NF-kappaB-dependent iNOS and proinflammatory cytokines production.
AB  - BACKGROUND AND PURPOSE: Glycyrrhizae radix has been widely used as a
      cytoprotective, plant-derived medicine. We have identified a flavanoid,
      liquiritigenin, as an active component in extracts of Glycyrrhizae radix. This
      research investigated the effects of liquiritigenin on the induction of inducible
      NOS (iNOS) and proinflammatory cytokines by lipopolysaccharide (LPS) in Raw264.7
      cells, and on paw oedema in rats. EXPERIMENTAL APPROACH: iNOS expression was
      determined by western blotting, real-time reverse transcription-PCR and reporter
      gene analyses. Tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta
      and IL-6 were assayed by ELISA. Gel shift assay and immunoblotting were used to
      assess NF-kappaB activation. The effect of liquiritigenin on acute inflammation
      in vivo was evaluated using carrageenan-induced paw oedema. KEY RESULTS:
      Treatment of Raw264.7 cells with liquiritigenin caused inhibition of LPS-induced
      NF-kappaB DNA binding activity, due to repression of I-kappaBalpha
      phosphorylation and degradation. Liquiritigenin treatment prevented LPS from
      increasing the levels of iNOS protein and mRNA in a concentration-dependent
      manner. Liquiritigenin also suppressed the production of TNF-alpha, IL-1beta and
      IL-6 from Raw264.7 cells after LPS. In rats, liquiritigenin treatment inhibited
      formation of paw oedema induced by carrageenan. CONCLUSION AND IMPLICATIONS:
      These results demonstrate that liquiritigenin exerts anti-inflammatory effects,
      which results from the inhibition of NF-kappaB activation in macrophages, thereby
      decreasing production of iNOS and proinflammatory cytokines. Our findings showing
      inhibition by liquiritigenin of paw oedema as well as inflammatory gene induction
      will help to understand the pharmacology and mode of action of liquiritigenin,
      and of the anti-inflammatory use of Glycyrrhizae radix.

PMID- 18332857
TI  - The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of
      Parkinson's disease through inhibition of monoamine oxidase B.
AB  - BACKGROUND AND PURPOSE: The peroxisome proliferator-activated receptor-gamma
      (PPARgamma) agonist pioglitazone has previously been shown to attenuate
      dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
      mouse model of Parkinson's disease, an effect attributed to its anti-inflammatory
      properties. In the present investigation, we provide evidence that pioglitazone
      is effective in the MPTP mouse model, not via an anti-inflammatory action, but
      through inhibition of MAO-B, the enzyme required to biotransform MPTP to its
      active neurotoxic metabolite 1-methyl-4-phenylpyridinium (MPP+). EXPERIMENTAL
      APPROACH: Mice were treated with pioglitazone (20 mg kg(-1) b.i.d. (twice a day),
      p.o., for 7 days), prior and post or post-MPTP (30 mg kg(-1) s.c.) treatment.
      Mice were then assessed for motor impairments on a beam-walking apparatus and for
      reductions in TH immunoreactivity in the substantia nigra and depletions in
      striatal dopamine. The effects of pioglitazone on striatal MPP+ levels and MAO-B
      activity were also assessed. KEY RESULTS: Mice treated with MPTP showed deficits
      in motor performance, marked depletions in striatal dopamine levels and a
      concomitant reduction in TH immunoreactivity in the substantia nigra.
      Pretreatment with pioglitazone completely prevented these effects of MPTP.
      However, pretreatment with pioglitazone also significantly inhibited the MPTP
      induced production of striatal MPP+ and the activity of MAO-B in the striatum.
      CONCLUSIONS AND IMPLICATIONS: The neuroprotection observed with pioglitazone
      pretreatment in the MPTP mouse model was due to the blockade of the conversion of
      MPTP to its active toxic metabolite MPP+, via inhibition of MAO-B.

PMID- 18332858
TI  - Inhalant abuse among adolescents: neurobiological considerations.
AB  - Experimentation with volatile substances (inhalants) is common during early
      adolescence, yet limited work has been conducted examining the neurobiological
      impact of regular binge use during this key stage of development. Human studies
      consistently demonstrate that chronic use is associated with significant toxic
      effects, including neurological and neuropsychological impairment, as well as
      diffuse and subtle changes in white matter. However, most preclinical research
      has tended to focus on acute exposure, with limited work examining the
      neuropharmacological or toxicological mechanisms underpinning these changes or
      their potential reversibility with abstinence. Nevertheless, there is growing
      evidence that commonly abused inhalants share common cellular mechanisms, and
      have similar actions to other drugs of abuse. Indeed, the majority of acute
      behavioural effects appear to be underpinned by changes in receptor and/or ion
      channel activity (for example, GABA(A), glycine and 5HT(3) receptor activation,
      NMDA receptor inhibition), although nonspecific interactions can also arise at
      high concentrations. Recent studies examining the effects of toluene exposure
      during the early postnatal period are suggestive of long-term alterations in the
      function of NMDA and GABA(A) receptors, although limited work has been conducted
      investigating exposure during adolescence. Given the critical role of
      neurotransmitter systems in cognitive, emotional and brain development, future
      studies will need to take account of the substantial neuromaturational changes
      that are known to occur in the brain during childhood and adolescence, and to
      specifically investigate the neuropharmacological and toxicological profile of
      inhalant exposure during this period of development.

PMID- 18332859
TI  - Endothelium removal augments endothelium-independent vasodilatation in rat
      mesenteric vascular bed.
AB  - BACKGROUND AND PURPOSE: The vascular endothelium regulates vascular tone by
      releasing various endothelium-derived vasoactive substances to counteract excess
      vascular response. We investigated whether the vascular endothelium regulates
      vasodilatation via released endothelium-derived contracting factors (EDCFs), by
      examining the effect of endothelium removal on responses to periarterial nerve
      stimulation (PNS) and various vasodilator agents. EXPERIMENTAL APPROACH: The rat
      mesenteric vascular bed was perfused with Krebs solution. Vasodilator responses
      to PNS and 5 min perfusion of vasodilator agents in preparations with endothelium
      were compared with those in the same preparations without endothelium. The
      endothelium was removed by 30 s perfusion with sodium deoxycholate. KEY RESULTS:
      Endothelium removal significantly augmented vasodilator responses to PNS and
      calcitonin gene-related peptide (CGRP), isoprenaline (beta-adrenoceptor agonist),
      SNP and 8-bromo-cGMP (8-Br-cGMP; cGMP analogue) but not BAY41-2272 (soluble
      guanylate cyclase activator). The augmentation of SNP-induced vasodilatation
      after denudation was much greater than that of CGRP- or isoprenaline-induced
      vasodilatation. In the preparations with an intact endothelium, L-NAME (nitric
      oxide synthase inhibitor) significantly augmented vasodilator responses to PNS
      and CGRP, isoprenaline, SNP and 8-Br-cGMP, but not BAY41-2272. Indomethacin
      (cyclooxygenase inhibitor) and seratrodast (thromboxane A(2) receptor
      antagonist), but not phosphoramidon (endothelin-1-converting enzyme inhibitor) or
      BQ-123 (selective endothelin type A receptor antagonists), significantly
      augmented vasodilator responses to PNS and CGRP, isoprenaline, SNP and BAY41
      2272. CONCLUSION AND IMPLICATION: These results suggest that the endothelium in
      rat mesenteric arteries regulates and maintains vascular tone via counteracting
      not only vasoconstriction through releasing endothelium-derived relaxing factors,
      but also vasodilatation, in part by releasing an EDCF, thromboxane A(2).

PMID- 18332860
TI  - Vardenafil protects isolated rat hearts at reperfusion dependent on GC and PKG.
AB  - BACKGROUND AND PURPOSE: The type-5 PDE inhibitor vardenafil reduces myocardial
      infarct size in situ, following ischemia/reperfusion, when applied at reperfusion
      in animal models. Little is known about the underlying protective signaling.
      Here, we test whether vardenafil is protective in rat isolated hearts and in a
      cell model of calcium stress. EXPERIMENTAL APPROACH: Infarct size in rat isolated
      hearts was measured after a 30 min regional ischemia and 120 min reperfusion.
      Vardenafil (1 nM-1 microM) was infused during reperfusion. HL-1 cardiomyocytes
      were loaded with tetramethylrhodamine ethyl ester (TMRE), a fluorescent marker of
      mitochondrial membrane potential (psi m). KEY RESULTS: Vardenafil at reperfusion
      reduced infarct size as percentage of the ischemic zone from 45.8+/-2.0% in
      control hearts to 26.2+/-2.7% (P<0.001) only at 10 nM, whereas higher or lower
      dosages failed to protect. This protective effect was blocked by co
      administration of either the GC inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin
      1-one (ODQ), or the PKG inhibitor, KT-5823. HL-1 cardiomyocytes, loaded with
      TMRE, were treated for 80 min with the calcium ionophore, calcimycin, to induce
      calcium stress. This reduced the mean cell fluorescence to 63.3 +/- 3.8% of
      baseline values and vardenafil protected against this fall (78.6 +/- 3.6%,
      P<0.01). The vardenafil-induced protection of HL-1 cells was blocked by ODQ, KT
      5823 or the PKG-inhibiting peptides DT-2 and DT-3, confirming a role for GC and
      PKG. CONCLUSIONS AND IMPLICATIONS: These results further support the hypothesis
      that PDE-5 inhibitors are protective in ischemic hearts, in addition to their
      known clinical effects in the treatment of erectile dysfunction in men.

PMID- 18332861
TI  - Rapid degradation of hypoxia-inducible factor-1alpha by KRH102053, a new
      activator of prolyl hydroxylase 2.
AB  - BACKGROUND AND PURPOSE: Hypoxia-inducible factor (HIF) is a transcription factor
      induced by hypoxia and degraded by ubiquitin-dependent proteasomes in normoxic
      conditions. Under hypoxic conditions, hydroxylation of HIF-1alpha subunit by
      prolyl hydroxylase (PHD) is suppressed, thus leading to increased levels of HIF.
      Although PHD2 plays a key role in regulating the levels of HIF, chemical
      activators of PHD2 are relatively unknown. The aim of this study was to identify
      small molecule activators of PHD2 that could be used, eventually, to suppress the
      level of HIF-1alpha. EXPERIMENTAL APPROACH: By using the overproduced PHD2 as a
      target, a molecular library consisting of more than 600 small molecules with a
      benzopyran structure was screened with an HPLC assay method. KEY RESULTS: We
      found a potent activator of PHD2, KRH102053 (2-amino-4-methylsulphanyl-butylic
      acid-4-methoxy-6-(4-methoxy-benzylamino)-2,2-dimethyl-chroman-3-yl ester). The
      effects of KRH102053 on controlling HIF were studied in human HOS osteosarcoma,
      rat PC12 phaeochromocytoma and human HepG2 hepatoma cells. Under our experimental
      conditions, KRH102053 decreased the protein level of HIF-1alpha and the mRNA
      levels of HIF-regulated downstream target genes, such as vascular endothelial
      growth factor, aldolase A, enolase 1 and monocarboxylate transporter 4.
      Consistent with these results, KRH102053 also inhibited the rates of HIF-related
      migration and invasion of HOS cells as well as the degree of tube formation in
      human umbilical vein endothelium cells. CONCLUSIONS AND IMPLICATIONS: These
      results suggest that KRH102053 and its structural analogues have the potential
      for use as therapeutic agents against various diseases associated with HIF.

PMID- 18332862
TI  - Rifampin and digoxin induction of MDR1 expression and function in human
      intestinal (T84) epithelial cells.
AB  - BACKGROUND AND PURPOSE: Oral drug bioavailability is limited by intestinal
      expression of P-glycoprotein (MDR1, Pgp, ABCB1) whose capacity is regulated via
      nuclear receptors e.g. the pregnane X receptor (PXR, SXR, NR1I2). In order to
      study dynamic regulation of MDR1 transport capacity we have identified the T84
      epithelial cell-line as a model for human intestine co-expressing MDR1 with PXR.
      The ability of rifampin, a known PXR agonist and digoxin, a model MDR1 substrate,
      to regulate MDR1 expression and transport activity has been tested, in these T84
      cells. EXPERIMENTAL APPROACH: Transport was assayed by bi-directional [(3)H]
      digoxin transepithelial fluxes across epithelial layers of T84 cells seeded onto
      permeable filter supports following pre-exposure to rifampin and digoxin.
      Quantitative real-time PCR, Western blotting and immunocytochemistry were used to
      correlate induction of MDR1 transcript and protein levels with transport
      activity. KEY RESULTS: Rifampin exposure (10 microM, 72 hours) increased MDR1
      transcript levels (3.4 fold), MDR1 total protein levels (4.4 fold), apical MDR1
      protein (2.7 fold) and functional activity of MDR1 (1.2 fold). Pre-incubation
      with digoxin (1 microM, 72 hours) potently induced MDR1 transcript levels (92
      fold), total protein (7 fold), apical MDR1 protein (4.7 fold) and functional
      activity (1.75 fold). Whereas PXR expression was increased by rifampin incubation
      (2 fold), digoxin reduced PXR expression (0.3 fold). CONCLUSIONS AND
      IMPLICATIONS: Chronic digoxin pre-treatment markedly upregulates MDR1 expression
      and secretory capacity of T84 epithelia. Digoxin-induced changes in MDR1 levels
      are distinct from PXR-mediated changes resulting from rifampin exposure.

PMID- 18332863
TI  - Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion
      via P-selectin suppression during inflammation.
AB  - BACKGROUND AND PURPOSE: The Na(+)/H(+) exchange (NHE) inhibitor cariporide is
      known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic
      Ca(2+) overload. Leukocyte activation and infiltration also mediates I/R injury
      but whether cariporide reduces I/R injury by affecting leukocyte activation is
      unknown. We studied the effect of cariporide on thrombin and I/R induced
      leukocyte activation and infiltration models and examined P-selectin expression
      as a potential mechanism for any identified effects. EXPERIMENTAL APPROACH: An in
      vivo rat mesenteric microcirculation microscopy model was used with stimulation
      by thrombin (0.5 micro ml(-1)) superfusion or ischaemia (by haemorrhagic shock
      for 60 min) and reperfusion (90 min). KEY RESULTS: Treatment with cariporide (10
      mg kg(-1) i.v.) significantly reduced leukocyte rolling, adhesion and
      extravasation after thrombin exposure. Similarly, cariporide reduced leukocyte
      rolling (54+/-6.2 to 2.4+/-1.0 cells min(-1), P<0.01), adherence (6.3+/-1.9 to
      1.2+/-0.4 cells 100 microm(-1), P<0.01) and extravasation (9.1+/-2.1 to 2.4+/-1.1
      cells per 20 x 100 microm perivascular space, P<0.05), following haemorrhagic
      shock induced systemic ischaemia and reperfusion. The cell adhesion molecule P
      selectin showed a profound decrease in endothelial expression following
      cariporide administration in both thrombin and I/R stimulated groups (35.4+/-3.2
      vs 14.2+/-4.1% P-selectin positive cells per tissue section, P<0.01). CONCLUSIONS
      AND IMPLICATIONS: The NHE inhibitor cariporide is known to limit reperfusion
      injury by controlling Ca(2+) overload but these data are novel evidence for a
      vasculoprotective effect of NHE inhibition at all levels of leukocyte activation,
      an effect which is likely to be mediated at least in part by a reduction of P
      selectin expression.

PMID- 18332864
TI  - Identification of unique and common low abundance tumour-specific transcripts by
      suppression subtractive hybridization and oligonucleotide probe array analysis.
AB  - Most human cancers are characterized by genetic aberrations accompanied by
      altered expression and function of numerous genes. Applying genome-wide,
      microarray gene expression analysis to identify deregulated genes in different
      tumour types can provide potential gene candidates as diagnostic and prognostic
      tools and promising targets for drug development. However, the detection of
      deregulated genes with low levels of expression remains a major challenge. In
      this study, we have designed a strategy, termed modified suppression subtractive
      hybridization (mSSH), to identify genes encoding rare transcripts. The strategy
      entails incorporating the T(7)-promoter sequence at the 5' end of the noncoding
      cDNA strand during first strand cDNA synthesis to generate unidirectional
      antisense RNA from the resultant cDNA following conventional SSH. These
      transcripts are subsequently analysed by Affymetrix oligonucleotide gene arrays.
      Here, we have used five hepatocellular carcinoma (HCC), five breast carcinoma and
      four nasopharyngeal carcinoma (NPC) biopsies separately as testers and their
      corresponding normal biopsies as drivers to enrich for low abundance tumour type
      specific transcripts. The total detectable number of probe sets following mSSH
      was reduced almost 10-fold in comparison to those detected for the same resected
      tumour tissues without undergoing subtraction, thus yielding a subtraction
      efficacy of over 90%. Using this experimental approach, we have identified 48 HCC
      specific, 45 breast carcinoma-specific, and 83 NPC-specific genes. In addition,
      115 genes were upregulated in all the three cancer types. When compared to gene
      profiling data obtained without mSSH, the majority of these identified
      transcripts were of low abundance in the original cancer tissues. mSSH can
      therefore serve as a comprehensive molecular strategy for pursuing functional
      genomic studies of human cancers.

PMID- 18332865
TI  - Suppression of PTEN function increases breast cancer chemotherapeutic drug
      resistance while conferring sensitivity to mTOR inhibitors.
AB  - Ectopic expression of mutant forms of phosphatase and tensin homologue deleted on
      chromosome 10 (PTEN) lacking lipid (G129E) or lipid and protein (C124S)
      phosphatase activity decreased sensitivity of MCF-7 breast cancer cells, which
      have wild-type PTEN, to doxorubicin and increased sensitivity to the mammalian
      target of rapamycin (mTOR) inhibitor rapamycin. Cells transfected with a mutant
      PTEN gene lacking both lipid and protein phosphatase activities were more
      resistant to doxorubicin than cells transfected with the PTEN mutant lacking
      lipid phosphatase activity indicating that the protein phosphatase activity of
      PTEN was also important in controlling the sensitivity to doxorubicin, while no
      difference was observed between the lipid (G129E) and lipid and protein (C124S)
      phosphatase PTEN mutants in terms of sensitivity to rapamycin. A synergistic
      inhibitory interaction was observed when doxorubicin was combined with rapamycin
      in the phosphatase-deficient PTEN-transfected cells. Interference with the lipid
      phosphatase activity of PTEN was sufficient to activate Akt/mTOR/p70S6K
      signaling. These studies indicate that disruption of the normal activity of the
      PTEN phosphatase can have dramatic effects on the therapeutic sensitivity of
      breast cancer cells. Mutations in the key residues which control PTEN lipid and
      protein phosphatase may act as dominant-negative mutants to suppress endogenous
      PTEN and alter the sensitivity of breast cancer patients to chemo- and targeted
      therapies.

PMID- 18332866
TI  - hSMG-1 and ATM sequentially and independently regulate the G1 checkpoint during
      oxidative stress.
AB  - Genotoxic stress activates the phosphatidylinositol 3-kinase-like kinases (PIKKs)
      that phosphorylate proteins involved in cell cycle arrest, DNA repair and
      apoptosis. Previous work showed that the PIKK ataxia telangiectasia mutated (ATM)
      but not ATM and Rad3 related phosphorylates p53 (Ser15) during hyperoxia, a model
      of prolonged oxidative stress and DNA damage. Here, we show hSMG-1 is responsible
      for the rapid and early phosphorylation of p53 (Ser15) and that ATM helps
      maintain phosphorylation after 24 h. Despite reduced p53 phosphorylation and
      abundance in cells depleted of hSMG-1 or ATM, levels of the p53 target p21 were
      still elevated and the G(1) checkpoint remained intact. Conditional
      overexpression of p21 in p53-deficient cells revealed that hyperoxia also
      stimulates wortmannin-sensitive degradation of p21. siRNA depletion of hSMG-1 or
      ATM restored p21 stability and the G(1) checkpoint during hyperoxia. These
      findings establish hSMG-1 as a proximal regulator of DNA damage signaling and
      reveal that the G(1) checkpoint is tightly regulated during prolonged oxidative
      stress by both PIKK-dependent synthesis and proteolysis of p21.

PMID- 18332867
TI  - Isosilybin B causes androgen receptor degradation in human prostate carcinoma
      cells via PI3K-Akt-Mdm2-mediated pathway.
AB  - The identification and development of novel nontoxic phytochemicals that target
      androgen and androgen receptor (AR) signaling remains a priority for prostate
      cancer (PCA) control. In the present study, we assessed the antiandrogenic
      efficacy of isosilybin B employing human PCA LNCaP (mutated AR), 22Rv1 (mutated
      AR) and LAPC4 (wild-type AR) cells. Isosilybin B (10-90 microM) treatment
      decreased the AR and prostate specific antigen (PSA) levels in LNCaP, 22Rv1 and
      LAPC4 cells, but not in non-neoplastic human prostate epithelial PWR-1E cells.
      Isosilybin B treatment also inhibited synthetic androgen R1881-induced nuclear
      localization of AR, PSA expression and cell growth, and caused G(1) arrest. In
      mechanistic studies identifying AR degradation, isosilybin B caused increased
      phosphorylation of Akt (Ser-473 and Thr-308) and Mdm2 (Ser-166), which was linked
      with AR degradation as pretreatment with PI3K inhibitor (LY294002)-restored AR
      level. Further, overexpression of kinase-dead Akt largely reversed isosilybin B
      mediated-AR degradation suggesting a critical role of Akt in AR degradation.
      Antibody pull-down results also indicated that isosilybin B treatment enhances
      the formation of complex between Akt, Mdm2 and AR, which promotes phosphorylation
      dependent AR ubiquitination and its degradation by proteasome. Together, present
      findings identify a novel mechanism for isosilybin B-mediated anticancer effects
      in human PCA cells.

PMID- 18332868
TI  - VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation.
AB  - Inactivation of the neurofibromatosis type 2 (NF2) tumor suppressor gene function
      has been observed not only in familial schwannomas and other central nervous
      system tumors, but also in malignant tumors unrelated to the NF2 syndrome,
      indicating a broader role of NF2 in human tumorigenesis. The NF2-encoded protein
      Merlin is closely related to the Ezrin-Radixin-Moesin family of
      membrane/cytoskeleton linker proteins, and has been demonstrated to suppress
      tumor growth by inhibiting extracellular signal-regulated kinase (ERK) and Rac1
      activation. Interestingly, serum deprivation has been shown to regulate Merlin at
      the protein level, however, exactly how such condition affects Merlin remains
      elusive. In this study, we provide evidence to show that Merlin is regulated in a
      Roc1-Cullin4A-DDB1-dependent manner. Following serum stimulation, Merlin is
      recruited to the E3 ligase complex through a direct interaction with the WD40
      containing adaptor protein VprBP. Loading of Merlin to the E3 ubiquitin ligase
      complex resulted in its polyubiquitination, and consequently its proteasome
      mediated degradation. Consistently, VprBP depletion abolished the in vivo
      interaction of Merlin and Roc1-Cullin4A-DDB1, which resulted in Merlin
      stabilization and inhibited ERK and Rac activation. Together, our data revealed a
      novel regulatory mechanism for the tumor suppressor function of Merlin.

PMID- 18332869
TI  - Retinoblastoma protein modulates gankyrin-MDM2 in regulation of p53 stability and
      chemosensitivity in cancer cells.
AB  - MDM2 is a key ubiquitin E3 ligase for p53 and its activity is critically
      regulated by a set of modulators, including ARF, p300, YY1 and recently by
      gankyrin, an oncoprotein frequently overexpressed in human heptocellular
      carcinomas. We have previously shown that MDM2 binds to and promotes
      retinoblastoma protein (Rb) degradation. Here we show that Rb inhibits MDM2 E3
      ligase activity resulting in stabilization of p53. In addition, we demonstrated
      that Rb inhibits MDM2-mediated p53 ubiquitination in a gankyrin-dependent manner
      and the Rb-gankyrin interaction is critical for Rb-induced p53 stabilization.
      Furthermore, acute ablation of Rb facilitates gankyrin-mediated p53
      destabilization, and desensitizes cancer cells for chemotherapy-induced
      apoptosis. These results indicate that Rb antagonizes gankyrin to inhibit MDM2
      mediate p53 ubiquitination in cancer cells and suggest that the status of both
      p53 and Rb is important for efficacy of cancer chemotherapy.

PMID- 18332870
TI  - Cisplatin treatment increases survival and expansion of a highly tumorigenic side
      population fraction by upregulating VEGF/Flt1 autocrine signaling.
AB  - The cellular and molecular mechanisms of tumor progression following chemotherapy
      are largely unknown. Here, we demonstrate that cisplatin (CDDP) treatment
      upregulates VEGF and Flt1 expression leading to the survival and expansion of a
      highly tumorigenic fraction of side-population (SP) cells in osteosarcoma (HOS),
      neuroblastoma (SK-N-BE2) and rhabdomyosarcoma (RH-4) cell lines. In all three
      lines, we show that CDDP treatment increases levels of VEGF and Flt1 expression,
      and induces enhanced clonogenic capacity and increased expression of the
      'stemness'-associated genes Nanog, Bmi-1 and Oct-4 in the SP fraction. In HOS,
      these changes are associated with the transformation of a non-tumorigenic
      osteosarcoma SP fraction to a highly tumorigenic phenotype. Inhibition of Flt1
      led to complete reduction of tumorigenicity in the HOS SP fraction, and reduction
      of clonogenic capacity and expression of stemness genes in the SK-N-BE(2) and RH
      4 SP fractions. Treatment with U0126, a specific inhibitor of MAPK/ERK1,2
      completely downregulates CDDP-induced VEGF and Flt1 expression and
      induction/expansion of SP fraction in all three cell lines, indicating that these
      effects are mediated through MAPK/ERK1,2 signaling. In conclusion, we report a
      novel mechanism of CDDP-induced tumor progression, whereby the activation of
      VEGF/Flt1 autocrine signaling leads to the survival and expansion of a highly
      tumorigenic SP fraction.

PMID- 18332871
TI  - Activation of peroxisome proliferator-activated receptor-gamma by curcumin blocks
      the signaling pathways for PDGF and EGF in hepatic stellate cells.
AB  - During hepatic fibrogenesis, reduction in the abundance of peroxisome
      proliferator-activated receptor-gamma (PPARgamma) is accompanied by activation of
      mitogenic signaling for platelet-derived growth factor (PDGF) and epidermal
      growth factor (EGF) in hepatic stellate cells (HSCs), the major effector cells.
      We previously reported that curcumin, the yellow pigment in curry, interrupted
      PDGF and EGF signaling, stimulated PPARgamma gene expression, and enhanced its
      activity, leading to inhibition of cell proliferation of activated HSC in vitro
      and in vivo. The aim of this study was to elucidate the underlying mechanisms. We
      hypothesized that the enhancement of PPARgamma activity by curcumin might result
      in the interruption of PDGF and EGF signaling. Our experiments demonstrated that
      curcumin, with different treatment strategies, showed different efficiencies in
      the inhibition of PDGF- or EGF-stimulated HSC proliferation. Further experiments
      observed that curcumin dose dependently reduced gene expression of PDGF and EGF
      receptors (ie, PDGF-betaR and EGFR), which required PPARgamma activation. The
      activation of PPARgamma by its agonist suppressed pdgf-betar and egfr expression
      in HSC. In addition, curcumin reduced the phosphorylation levels of PDGF-betaR
      and EGFR, as well as their downstream signaling cascades, including ERK1/2 and
      JNK1/2. Moreover, activation of PPARgamma induced gene expression of glutamate
      cysteine ligase, the rate-limiting enzyme in de novo synthesis of the major
      intracellular antioxidant, glutathione. De novo synthesis of glutathione was
      required for curcumin to suppress pdgf-betar and egfr expression in activated
      HSCs. Our results collectively demonstrated that enhancement of PPARgamma
      activity by curcumin interrupted PDGF and EGF signaling in activated HSCs by
      reducing the phosphorylation levels of PDGF-betaR and EGFR, and by suppressing
      the receptor gene expression. These results provide novel insights into the
      mechanisms of curcumin in the inhibition of HSC activation and the suppression of
      hepatic fibrogenesis.

PMID- 18332872
TI  - Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer
      cell lines.
AB  - HER2 and TOP2A are targets for the therapeutic agents trastuzumab and
      anthracyclines and are frequently amplified in breast cancers. The aims of this
      study were to provide a detailed molecular genetic analysis of the 17q12-q21
      amplicon in breast cancers harbouring HER2/TOP2A co-amplification and to
      investigate additional recurrent co-amplifications in HER2/TOP2A-co-amplified
      cancers. In total, 15 breast cancers with HER2 amplification, 10 of which also
      harboured TOP2A amplification, as defined by chromogenic in situ hybridisation,
      and 6 breast cancer cell lines known to be amplified for HER2 were subjected to
      high-resolution microarray-based comparative genomic hybridisation analysis. This
      revealed that the genomes of 12 cases were characterised by at least one
      localised region of clustered, relatively narrow peaks of amplification, with
      each cluster confined to a single chromosome arm (ie 'firestorm' pattern) and 3
      cases displayed many narrow segments of duplication and deletion affecting the
      vast majority of chromosomes (ie 'sawtooth' pattern). The smallest region of
      amplification (SRA) on 17q12 in the whole series extended from 34.73 to 35.48 Mb,
      and encompassed HER2 but not TOP2A. In HER2/TOP2A-co-amplified samples, the SRA
      extended from 34.73 to 36.54 Mb, spanning a region of approximately 1.8 Mb. Apart
      from HER2 and TOP2A, this region encompassed four additional genes whose
      expression levels as defined by quantitative real-time PCR are significantly
      higher in HER2/TOP2A-co-amplified vs HER2-amplified breast cancers: CASC3, CDC6,
      RARA and SMARCE1. Of the cell lines studied, SKBR3 and UACC812 showed HER2/TOP2A
      co-amplification. In conclusion, this is the first detailed genome-wide
      characterisation of HER2/TOP2A-amplified breast cancers; cell lines were
      identified that can be used to model these cancers in vitro. The 17q12 amplicon
      is complex and harbours multiple genes that may be associated with breast cancer
      development and progression, and potentially exploitable as therapeutic targets.

PMID- 18332873
TI  - High-resolution array comparative genomic hybridization analysis of human
      bronchial and salivary adenoid cystic carcinoma.
AB  - Adenoid cystic carcinoma (ACC) is a rare but distinctive tumor. Oligonucleotide
      array comparative genomic hybridization has been applied for cataloging genomic
      copy number alterations (CNAs) in 17 frozen salivary or bronchial tumors. Only
      four whole chromosome CNAs were found, and most cases had 2-4 segmental CNAs. No
      high level amplification was observed. There were recurrent gains at 7p15.2,
      17q21-25, and 22q11-13, and recurrent losses at 1p35, 6q22-25, 8q12-13, 9p21,
      12q12-13, and 17p11-13. The minimal region of gain at 7p15.2 contained the HOXA
      cluster. The minimal common regions of deletions contained the CDKN2A/CDKN2B,
      TP53, and LIMA1 tumor suppressor genes. The recurrent deletion at 8q12.3-13.1
      contained no straightforward tumor suppressor gene, but the MIRN124A2 microRNA
      gene, whose product regulates MMP2 and CDK6. Among unique CNAs, gains harbored
      CCND1, KIT/PDGFRA/KDR, MDM2, and JAK2. The CNAs involving CCND1, MDM2, KIT,
      CDKN2A/2B, and TP53 were validated by FISH and/or multiplex ligation-dependent
      probe amplification. Although most tumors overexpressed cyclin D1 compared with
      surrounding glands, the only case to overexpress MDM2 had the corresponding CNA.
      In conclusion, our report suggests that ACC is characterized by a relatively low
      level of structural complexity. Array CGH and immunohistochemical data implicate
      MDM2 as the oncogene targeted at 12q15. The gain at 4q12 warrants further
      exploration as it contains a cluster of receptor kinase genes (KIT/PDGFRA/KDR),
      whose products can be responsive to specific therapies.

PMID- 18332874
TI  - Metallothionein 1G acts as an oncosupressor in papillary thyroid carcinoma.
AB  - The molecular pathogenesis of tumors arising from the thyroid follicular
      epithelial cells, including papillary (PTC) and follicular thyroid carcinoma
      (FTC), is only partially understood, and the role of tumor suppressor genes has
      not yet been assessed. The metallothionein (MT) gene family encodes a class of
      metal-binding proteins involved in several cellular processes, and their
      expression is often deregulated in human tumors. Recently, downregulation of MT
      gene expression in PTC has been reported, suggesting a possible oncosuppressor
      role of this gene family in the pathogenesis of thyroid tumors. To further
      explore this possibility, we performed expression and functional studies.
      Analysis of microarray data of thyroid tumors of different histologic types
      showed that several MT genes were downregulated with respect to normal tissue.
      The microarray data were corroborated by quantitative PCR experiments, showing
      downregulation of MTs in PTC and FTC, but to a greater extent in papillary
      carcinoma. The expression of MTs was also investigated at the protein level by
      immunohistochemistry; the results were consistent with the microarray data,
      showing general downregulation in tumor samples, which was more evident in PTC.
      The functional consequence of MT downregulation was addressed employing an
      experimental model made of the PTC-derived K1 cell line in which MT1G expression
      is repressed by promoter methylation. Restoration of MT1G expression by cDNA
      transfection affected growth rate and in vivo tumorigenicity of K1 cells,
      indicating an oncosuppressor role for MT1G in thyroid papillary tumorigenesis.

PMID- 18332875
TI  - Expression of cell adhesion molecule 1 in malignant pleural mesothelioma as a
      cause of efficient adhesion and growth on mesothelium.
AB  - Cell adhesion molecule 1 (CADM1), formerly referred to as SgIGSF, TSLC1, or Necl
      2, has been characterized as a mast-cell adhesion molecule that mediates
      efficient interactions with mesothelial cells. Here, we examined whether CADM1
      might be involved in the diffuse tumor growth over the pleural surface that
      characterizes malignant pleural mesothelioma (MPM). Immunohistochemical and
      western blot analyses revealed that 14 (25%) of 57 MPMs expressed the full-length
      form of CADM1 on the cell membrane, but non-neoplastic mesothelial cells did not
      express it at all. The majority of available MPM cell lines also expressed the
      full-length form of CADM1. We compared CADM1-positive and -negative MPM cells in
      culture within soft agar and in coculture on mesothelial or fibroblastic
      monolayers. Within soft agar, CADM1-negative MPM cells were capable of forming
      colonies, whereas CADM1-positive cells were not, suggesting that CADM1 is a
      potential tumor suppressor of MPM, consistent with the past characterization of
      this molecule in other types of tumors. However, in coculture on mesothelial cell
      monolayers lacking full-length CADM1, CADM1-positive MPM cells spread more widely
      and grew more quickly, whereas the CADM1-negative cells piled up. Transfection of
      the CADM1-negative cells with CADM1 cDNA caused them to behave like the CADM1
      positive cells, with faster, more widespread growth. These phenotypic differences
      were not detectable in cocultures on lung fibroblastic monolayers, in which all
      MPM cells grew much more slowly than on mesothelial cells, irrespective of CADM1
      positivity. CADM1 thus appears to mediate efficient adhesion and growth of MPM
      cells specifically on mesothelial cells, probably via trans-heterophilic binding,
      and thus may be involved in the manifestation of a considerable subset of MPMs as
      diffusely growing tumors disseminated over the pleural surface.

PMID- 18332876
TI  - A genome-wide association study in 574 schizophrenia trios using DNA pooling.
AB  - The cost of genome-wide association (GWA) studies can be prohibitively high when
      large samples are genotyped. We conducted a GWA study on schizophrenia (SZ) and
      to reduce the cost, we used DNA pooling. We used a parent-offspring trios design
      to avoid the potential problems of population stratification. We constructed
      pools from 605 unaffected controls, 574 SZ patients and a third pool from all the
      parents of the patients. We hybridized each pool eight times on Illumina
      HumanHap550 arrays. We estimated the allele frequencies of each pool from the
      averaged intensities of the arrays. The significance level of results in the
      trios sample was estimated on the basis of the allele frequencies in cases and
      non-transmitted pseudocontrols, taking into account the technical variability of
      the data. We selected the highest ranked SNPs for individual genotyping, after
      excluding poorly performing SNPs and those that showed a trend in the opposite
      direction in the control pool. We genotyped 63 SNPs in 574 trios and analysed the
      results with the transmission disequilibrium test. Forty of those were
      significant at P<0.05, with the best result at P=1.2 x 10(-6) for rs11064768.
      This SNP is within the gene CCDC60, a coiled-coil domain gene. The third best SNP
      (P=0.00016) is rs893703, within RBP1, a candidate gene for schizophrenia.

PMID- 18332877
TI  - Family-based association testing strongly implicates DRD2 as a risk gene for
      schizophrenia in Han Chinese from Taiwan.
AB  - The gene that codes for dopamine receptor D2 (DRD2 on chromosome 11q23) has long
      been a prime functional and positional candidate risk gene for schizophrenia.
      Collectively, prior case-control studies found a reliable effect of the Ser311Cys
      DRD2 polymorphism (rs1801028) on risk for schizophrenia, but few other
      polymorphisms in the gene had ever been evaluated and no adequately powered
      family-based association study has been performed to date. Our objective was to
      test 21 haplotype-tagging and all three known nonsynonymous single-nucleotide
      polymorphisms (SNPs) in DRD2 for association with schizophrenia in a family-based
      study of 2408 Han Chinese, including 1214 affected individuals from 616 families.
      We did not find a significant effect of rs1801028, but we did find significant
      evidence for association of schizophrenia with two multi-marker haplotypes
      spanning blocks of strong linkage disequilibrium (LD) and nine individual SNPs
      (Ps<0.05). Importantly, two SNPs (rs1079727 and rs2283265) and both multi-marker
      haplotypes spanning entire LD blocks (including one that contained rs1801028)
      remained significant after correcting for multiple testing. These results further
      add to the body of data implicating DRD2 as a schizophrenia risk gene; however, a
      causal variant(s) in DRD2 remains to be elucidated by further fine mapping of the
      gene, with particular attention given to the area surrounding the third through
      fifth exons.

PMID- 18332878
TI  - The genetics of bipolar disorder: genome 'hot regions,' genes, new potential
      candidates and future directions.
AB  - Bipolar disorder (BP) is a complex disorder caused by a number of liability genes
      interacting with the environment. In recent years, a large number of linkage and
      association studies have been conducted producing an extremely large number of
      findings often not replicated or partially replicated. Further, results from
      linkage and association studies are not always easily comparable. Unfortunately,
      at present a comprehensive coverage of available evidence is still lacking. In
      the present paper, we summarized results obtained from both linkage and
      association studies in BP. Further, we indicated new potential interesting genes,
      located in genome 'hot regions' for BP and being expressed in the brain. We
      reviewed published studies on the subject till December 2007. We precisely
      localized regions where positive linkage has been found, by the NCBI Map viewer
      (http://www.ncbi.nlm.nih.gov/mapview/); further, we identified genes located in
      interesting areas and expressed in the brain, by the Entrez gene, Unigene
      databases (http://www.ncbi.nlm.nih.gov/entrez/) and Human Protein Reference
      Database (http://www.hprd.org); these genes could be of interest in future
      investigations. The review of association studies gave interesting results, as a
      number of genes seem to be definitively involved in BP, such as SLC6A4, TPH2,
      DRD4, SLC6A3, DAOA, DTNBP1, NRG1, DISC1 and BDNF. A number of promising genes,
      which received independent confirmations, and genes that have to be further
      investigated in BP, have been also systematically listed. In conclusion, the
      combination of linkage and association approaches provided a number of liability
      genes. Nevertheless, other approaches are required to disentangle conflicting
      findings, such as gene interaction analyses, interaction with psychosocial and
      environmental factors and, finally, endophenotype investigations.

PMID- 18332879
TI  - Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in
      mediating behavioral displays related to behavioral symptoms of mania.
AB  - The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene
      resides in a genetic linkage region (6q21) associated with bipolar disorder
      (BPD), but its function in affective regulation is unknown. Compared with wild
      type (WT) and GluR5 knockout (KO) mice, GluR6 KO mice were more active in
      multiple tests and super responsive to amphetamine. In a battery of specific
      tests, GluR6 KO mice also exhibited less anxious or more risk-taking type
      behavior and less despair-type manifestations, and they also had more aggressive
      displays. Chronic treatment with lithium, a classic antimanic mood stabilizer,
      reduced hyperactivity, aggressive displays and some risk-taking type behavior in
      GluR6 KO mice. Hippocampal and prefrontal cortical membrane levels of GluR5 and
      KA-2 receptors were decreased in GluR6 KO mice, and chronic lithium treatment did
      not affect these decreases. The membrane levels of other glutamatergic receptors
      were not significantly altered by GluR6 ablation or chronic lithium treatment.
      Together, these biochemical and behavioral results suggest a unique role for
      GluR6 in controlling abnormalities related to the behavioral symptoms of mania,
      such as hyperactivity or psychomotor agitation, aggressiveness, driven or
      increased goal-directed pursuits, risk taking and supersensitivity to
      psychostimulants. Whether GluR6 perturbation is involved in the mood elevation or
      thought disturbance of mania and the cyclicity of BPD are unknown. The molecular
      mechanism underlying the behavioral effects of lithium in GluR6 KO mice remains
      to be elucidated.

PMID- 18332881
TI  - Relationship between adiposity and pedometer-assessed ambulatory activity in
      adult, rural African women.
AB  - PURPOSE: To investigate the association between adiposity and pedometry-assessed
      ambulation in a convenience sample of adult, rural black South African women.
      METHODS: Pedometry data were collected over 7 days in 121 subjects. Adiposity
      measures included body mass index (BMI), waist circumference (WC) and percentage
      body fat (PBF). RESULTS: Sedentarism (<5000 steps day(-1)) was found in 13.7%,
      while 39.7% were classified as accruing sufficient physical activity (>or=10 000
      steps day(-1)). Significant associations (P<0.02) existed between steps day(-1)
      and adiposity measures (r=-0.22 to -0.23). After adjusting for age, only BMI
      remained significantly associated with steps day(-1) (r=-0.20, P=0.032).
      Significant age-adjusted linear trends were found across combined BMI-WC risk
      categories for steps day(-1) (P=0.036). Adjusting for age, motor vehicle access,
      education, use of tobacco products and comorbidities, BMI decreased 1.4 kg m(-2)
      per 5000 steps day(-1) (P=0.035), access to a motor vehicle within the household
      increased PBF by 4% (P=0.018), and compared with sedentarism, the risk of obesity
      (BMI >or=30 kg m(-2)) was 52% lower at 10 000 steps day(-1) (P=0.028).
      CONCLUSION: Modest associations were found between adiposity and ambulation.
      Ambulation decreased the risk for obesity, while motor vehicle access was
      associated with increased adiposity levels.

PMID- 18332882
TI  - Increased visceral fat and decreased energy expenditure during the menopausal
      transition.
AB  - OBJECTIVE: This study assessed longitudinal changes in body composition, fat
      distribution and energy balance in perimenopausal women. We hypothesized that
      total fat and abdominal body fat would increase at menopause due to decreased
      energy expenditure (EE) and declining estrogen, respectively. DESIGN:
      Observational, longitudinal study with annual measurements for 4 years. SUBJECTS:
      Healthy women (103 Caucasian; 53 African-American), initially premenopausal.
      During follow-up, lack of menstruation for 1 year and follicle-stimulating
      hormone >30 mIU ml(-1) defined a subject as postmenopausal. MEASUREMENTS: Fat and
      lean mass (dual-energy X-ray absorptiometry), visceral (VAT) and subcutaneous
      abdominal fat (SAT) (computed tomography), dietary intake (4-day food record),
      serum sex hormones and physical activity (tri-axial accelerometry). Twenty-four
      hour EE was measured by whole-room calorimeter in a subset of 34 women at
      baseline and at year 4. RESULTS: Body fat and weight increased significantly over
      time only in those women who became postmenopausal by year 4 (n=51). All women
      gained SAT over time; however, only those who became postmenopausal had a
      significant increase in VAT. The postmenopausal group also exhibited a
      significant decrease in serum estradiol. Physical activity decreased
      significantly 2 years before menopause and remained low. Dietary energy, protein,
      carbohydrate and fiber intake were significantly higher 3-4 years before the
      onset of menopause compared with menopause onset. Twenty-four hour EE and
      sleeping EE decreased significantly with age; however, the decrease in sleeping
      EE was 1.5-fold greater in women who became postmenopausal compared with
      premenopausal controls (-7.9 vs -5.3%). Fat oxidation decreased by 32% in women
      who became postmenopausal (P<0.05), but did not change in those who remained
      premenopausal. CONCLUSION: Middle-aged women gained SAT with age, whereas
      menopause per se was associated with an increase in total body fat and VAT.
      Menopause onset is associated with decreased EE and fat oxidation that can
      predispose to obesity if lifestyle changes are not made.

PMID- 18332883
TI  - Motor unit number estimation of the tibialis anterior muscle in spinal cord
      injury.
AB  - STUDY DESIGN: Case-control study. OBJECTIVE: To investigate the number of motor
      units from the tibialis anterior (TA) muscle in normal subject and its change
      after SCI. SETTING: China Rehabilitation Research Center, Beijing, China.
      METHODS: Motor unit number estimation (MUNE) in 45 control subjects (35 young
      subjects with an average age of 36 years, and 10 elderly subjects with an average
      age of 65 years) was performed by using adapted multiple point stimulation method
      (AMPS). Twenty patients with SCI (10 subacute patients with an average age of 39
      years, and 10 chronic patients with an average age of 34 years) were also
      examined for three times in 3 months with the same method. RESULTS: The mean MUNE
      value of the TA muscle was 188+/-20 in the control group, and 40+/-33 in subacute
      SCI patients (P<0.01 vs young controls). A continuous increase in the MUNE value
      was observed in subacute SCI patients during the later follow-up period. In the
      chronic SCI group, the mean MUNE value was 173+/-29 which was similar to that of
      young control group. CONCLUSIONS: AMPS could be a useful procedure for
      quantifying changes of MUNE values after SCI. Changes in functional motor unit
      number may occur distal to the site of lesion in SCI patients. These phenomena
      may be caused by neuronal plasticity in motor units, reversible transsynaptic
      degeneration and/or local functional depression. Owing to the limited sample size
      and a wide age range of subjects recruited in this study, future study are
      warranted for revealing detailed changes of MUNE parameters after SCI and
      exploring the underlying mechanisms.

PMID- 18332884
TI  - Device-related complications of long-term intrathecal drug therapy via implanted
      pumps.
AB  - STUDY DESIGN: Case series. OBJECTIVES: To evaluate the risk of pump- and catheter
      related complications of intrathecal drug delivery systems. SETTING: Tertiary
      care center in Switzerland. METHODS: The medical records of all in- and out
      patient adults treated at our institution during a 12-year period were reviewed.
      All patients that had received intrathecal drug therapy via an implanted pump
      were invited to a structured interview. RESULTS: One hundred patients,
      representing therapy with 175 implanted pumps and 132 intrathecal catheters over
      552 years, participated in the study. During the observation period, 217 surgical
      procedures (including 100 primary pump implants) and 5863 pump refills were
      performed. The annual rate for complications requiring surgical measures was
      10.5%, with 35% being pump related and 65% being catheter related. The incidence
      of infections in our patients was 0.7% per year; all infections appeared during
      the first 3 months after implantation of the first pump. CONCLUSIONS:
      Complication rates of the patients treated in our center, where we have long-term
      experience with the indication, implantation and continuous care of patients with
      intrathecal infusion systems, are in the lowest ranges when compared with other
      published studies. We consider intrathecal testing before implantation,
      standardized perioperative procedures and consequent long-term care of the
      patients in a specialized outpatient clinic to be essential factors for the
      avoidance of complications.

PMID- 18332885
TI  - Idiopathic transverse myelitis presenting as the Brown-Sequard syndrome.
AB  - STUDY DESIGN: Case report. OBJECTIVES: To report an unusual case of Brown-Sequard
      syndrome (BSS) associated with idiopathic transverse myelitis (TM). SETTING:
      Department of Neurosurgery, Chonnam National University Hospital, Gwangju, South
      Korea. METHODS: A 38-year-old man presented with left leg weakness and right
      sided decrease in sensation at the T11 level below. Magnetic resonance images
      (MRI) of the thoracic spine showed diffuse swelling of the spinal cord spanning
      the fifth to the eighth thoracic vertebra. The lesion had high signal intensity
      on T2-weighted images. Eccentric nodular enhancement within the left
      anterolateral aspect of the spinal cord was appreciated with gadolinium
      administration. RESULTS: The patient was treated with pulsed methylprednisone and
      showed marked improvement in neurological function within 3 days. An MRI at 5
      month follow-up demonstrated complete resolution of the abnormalities.
      CONCLUSION: This case illustrates a rare case of BSS caused by idiopathic TM of
      the thoracic spinal cord. TM should be considered in the differential diagnosis
      of BSS.

PMID- 18332886
TI  - Translation and Australian validation of the spinal cord lesion-related coping
      strategies and emotional wellbeing questionnaires.
AB  - STUDY DESIGN: Representative community cross-sectional self-report survey of
      adults with spinal cord injury (SCI). OBJECTIVES: To establish semantic
      translation and validation of the Swedish scales--the Spinal Cord Lesion Coping
      Strategies Questionnaire and the Spinal Cord Lesion Emotional Wellbeing
      Questionnaire. SETTING: Adults on the Victorian traumatic SCI register and
      attendees of the nontraumatic outpatient clinic were invited to participate.
      METHODS: Instruments were forward and backward translated to establish semantic
      equivalence. Principle components analyses were undertaken. Correlation and
      logistic regression analyses were conducted to demonstrate validity of the
      instruments using both positive (high quality of life) and negative (depression
      and anxiety) psychological outcomes. RESULTS: The final sample consisted of 443
      adults with SCI living in the community. Both instruments demonstrated acceptable
      psychometric properties. Univariate correlation analyses showed most of the new
      scale components displayed medium to large relationships in the expected
      direction with the psychological outcomes and the other subscales. Health status
      and helplessness were significant predictors of both the positive and negative
      psychological outcomes in the logistic regression analyses. Acceptance was
      significantly related to the positive outcome only. Female and incomplete
      tetraplegia categories were significantly and positively related to depression
      only. CONCLUSION: Notwithstanding a few issues with some of the subscales, the
      results support the usefulness of these easy to use instruments and point to ways
      for further development of the scales.

PMID- 18332887
TI  - Current coronary heart disease risk assessment tools may underestimate risk in
      community-dwelling persons with chronic spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional, observational study. OBJECTIVES: To quantify, in
      adults with chronic spinal cord injury (SCI): (1) presence of metabolic syndrome
      versus the general North American population (GP) and (2) 10-year coronary heart
      disease (CHD) risk using Framingham risk scoring (FRS). SETTING: Ontario, Canada.
      METHODS: Fasting anthropometric and biochemical data were collected from 75
      adults with chronic SCI. Metabolic syndrome was determined using four
      internationally recognized definitions and FRS using the most recent (2001)
      algorithm. RESULTS: Prevalence of metabolic syndrome was up to 5.4 times lower in
      SCI participants compared to GP, and FRS categorized 3.1% of participants as
      being at high 10-year CHD risk. However, high-sensitivity C-reactive protein
      (CRP) values indicated 36.7% of participants as being at high CHD risk.
      CONCLUSION: Current metabolic syndrome definitions and FRS may underestimate true
      CHD risk in people with SCI. Tools that better identify CHD risk require
      validation in the SCI population. CRP may be a potential factor to consider in
      the development of SCI-specific screening tools.

PMID- 18332888
TI  - Health-related quality of life in persons with long-standing spinal cord injury.
AB  - STUDY DESIGN: A cross-sectional study of all patients with traumatic SCI admitted
      to Sunnaas Rehabilitation Hospital, Norway between 1961 and 1982. OBJECTIVES: To
      assess health-related quality of life (HRQOL) in persons with long-standing
      traumatic spinal cord injury (SCI) in Norway. SETTING: Sunnaas Rehabilitation
      Hospital, Norway. METHODS: Survey data and clinical examination of 165 persons
      with traumatic SCI of more than 20 years duration. HRQOL was assessed with the
      Norwegian 36-item short-form [corrected] (SF-36) Health Survey. The SF-36 results
      were compared with Norwegian norm data adjusted to age and gender. Differences in
      HRQOL between subgroups were studied. RESULTS: The persons with SCI exhibited
      significantly decreased HRQOL in the subscales for Physical Functioning, Bodily
      Pain, General Health, Social Functioning [corrected] and Vitality compared to the
      normal population. There were relatively small differences in HRQOL when
      comparing persons with paraplegia versus tetraplegia and persons with AIS (ASIA
      Impairment Scale; ASIA, American Spinal Injury Association) A-C versus D-E.
      Employed persons reported higher HRQOL compared to unemployed persons. HRQOL of
      individuals reporting health problems or symptoms was worse than those of
      individuals reporting no health problems at all. CONCLUSION: HRQOL is decreased
      in persons with long-standing SCI and especially in persons with comorbidity
      conditions.

PMID- 18332889
TI  - Hyperhidrosis treatment with bornaprine in the acute phase of spinal cord-injured
      patients.
AB  - STUDY DESIGN: Original article. OBJECTIVE: To test the use of bornaprine in the
      hyperhidrosis treatment in the acute phase of spinal cord-injured patients.
      SETTING: Patients with acute spinal cord lesions in the Spinal Unit of Pietra
      Ligure, Savona, Italy. METHOD: In 4 years, 12 patients have been treated, for a
      maximum period of 75 days, with dosages ranging from 2 to 4 mg day(-1). RESULTS:
      All of them reported long-lasting subjective benefits, without side effects, even
      after the interruption of the therapy. CONCLUSION: The bornaprine treatment, at 2
      or 4 mg day(-1) dosage, has been effective and safe to contrast hyperhidrosis, in
      the acute phase of spinal cord-injured patients. This positive experience would
      require additional trials and a larger number of cases to gain a more solid
      support.

PMID- 18332890
TI  - Use of Delta9-tetrahydrocannabinol in the treatment of spasticity in spinal cord
      injury patients.

PMID- 18332891
TI  - Measurement of carotid intima-media thickness to assess progression and
      regression of atherosclerosis.
AB  - Imaging modalities have been developed to assess atherosclerosis in vivo in the
      arterial wall because large clinical end-point studies are time-consuming and
      costly. Historically, in-hospital angiography and Doppler ultrasonography have
      been used to assess atherosclerosis development. Investigations of the arterial
      lumen are, however, increasingly being replaced by modalities that can measure
      changes in the arterial wall itself-intravascular ultrasonography, MRI and
      multislice CT. The fact that intravascular ultrasonography is invasive, CT
      involves substantial radiation exposure and requires contrast agents, and that
      MRI is time-consuming and technically challenging all limit the widespread use of
      these techniques. Moreover, all modalities have high associated costs. B-mode
      ultrasonographic imaging of the carotid arterial walls occupies a unique position
      in atherosclerosis research. This method enables sensitive, reproducible and
      noninvasive assessment of intima-media thickness (IMT) as a continuous variable.
      Epidemiological and clinical trial evidence as well as digitization and
      standardization have made carotid IMT a validated and accepted marker for
      generalized atherosclerosis burden and vascular disease risk. Here we describe
      the application of carotid IMT measurements as a tool in risk evaluation of
      individuals and in studies of atherosclerosis progression and regression.

PMID- 18332892
TI  - Ranolazine: a new antiarrhythmic agent for patients with non-ST-segment elevation
      acute coronary syndromes?

PMID- 18332893
TI  - C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed
      immunoglobulin G and albumin.
AB  - Blood platelets and C-reactive protein (CRP) are both used clinically as markers
      of ongoing inflammation, and both participate actively in inflammatory responses,
      although the biological effects are still incompletely understood. Rapidly
      adhering platelets express receptors for complement factor 1q (C1q) and the Fc
      part of immunoglobulin G (IgG), and CRP is known to activate/regulate complement
      via C1q binding, and to ligate FcgammaRs. In the present study, we used normal
      human IgG pre-adsorbed to a well-characterized methylated surface as a model
      solid-phase immune complex when investigating the effects of CRP and C1q on
      platelet adhesion and activation. Protein adsorption was characterized using
      ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non
      coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA
      was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q
      (markedly) decreased the spreading of adhering platelets. The combination of C1q
      and CRP was slightly more potent in reducing cell adhesion to IgG, and also
      impaired the adhesion to HSA and non-coated surfaces. Platelet production of
      thromboxane B2 (TXB(2)) was also reduced by C1q both in the presence and absence
      of CRP, whereas CRP alone had no effect on TXB(2) production. We conclude that
      CRP and C1q regulate the behaviour of platelets, and that this may be an
      important immunoregulatory mechanism during inflammatory conditions.

PMID- 18332894
TI  - Suppression of cytotoxic and proliferative xenogeneic T-cell responses by
      transgenic expression of indoleamine 2,3-dioxygenase.
AB  - Tryptophan catabolism initiated by the enzyme indoleamine 2,3-dioxygenase (IDO)
      has been postulated to be a natural regulatory mechanism for T cells. In this
      study, we generated a pig endothelial cell line expressing full-length human IDO
      (P-HuIDO) to serve as a simple model of a cellular xenogeneic graft. Splenocytes
      from mice primed to P-HuIDO cells were found to be as responsive to secondary
      stimulation as splenocytes from mice primed to parental cells. However, in T-cell
      proliferation assays using P-HuIDO cells as stimulators, a significant inhibition
      of both naive and memory xenogeneic proliferative responses was noted.
      Furthermore, the production of interferon-gamma and cytotoxic T lymphocyte
      function were also affected. When severe combined immunodeficiency mice were
      grafted with P-HuIDO cells, then challenged with primed splenocytes from BALB/c
      mice, cellular infiltration to the graft was delayed. Our findings suggest that
      transgenic expression of IDO in xenografts contributes to prolonged graft
      survival.

PMID- 18332895
TI  - Infectious diseases: too little, too late for tuberculosis.

PMID- 18332896
TI  - Assessment, diagnosis and treatment of a patient with hirsutism.
AB  - BACKGROUND: A 20-year-old woman presented with excess facial and body hair, which
      she had noticed for the first time after her menarche and which had gradually
      worsened since then. In addition, the patient's menstrual cycles had always been
      irregular. Her family history revealed that her mother also had a history of
      excess body hair. Among the patient's family members there was no other history
      of chronic diseases, including type 2 diabetes. She denied taking any regular
      medications and had been shaving and waxing regularly to remove the excess hair.
      On examination, the patient was a lean woman with normal vital signs. Prominent
      coarse hair was noted over her upper lip, chin, lower abdomen, lower back and
      upper legs. The remainder of the physical examination was unremarkable.
      INVESTIGATIONS: Physical examination, and investigations that included a
      transabdominal pelvic ultrasound scan and measurement of TSH, prolactin, 17
      hydroxyprogesterone and total testosterone levels. DIAGNOSIS: Hirsutism
      associated with polycystic ovary syndrome. MANAGEMENT: The patient was treated
      with cyproterone acetate 2 mg/day and ethinylestradiol 0.035 mg/day in
      combination with spironolactone 100 mg/day as well as with laser hair removal.
      The patient's symptoms had improved considerably after 1 year of treatment. A
      cardiometabolic risk assessment, including a standard oral glucose tolerance test
      and a lipid profile before and after treatment, revealed normal fasting and 2 h
      plasma glucose levels both at baseline and after 12 months, and a low-normal HDL
      cholesterol level that returned to normal after 12 months.

PMID- 18332897
TI  - Mechanisms of disease: advanced glycation end-products and their receptor in
      inflammation and diabetes complications.
AB  - Many important biochemical mechanisms are activated in the presence of high
      levels of glucose, which occur in diabetes. Elevated levels of glucose accelerate
      the formation of advanced glycation end-products (AGEs). Via their chief
      signaling receptor-the AGE-specific receptor (commonly abbreviated as RAGE)-AGEs
      generate reactive oxygen species and activate inflammatory signaling cascades.
      Consequently, AGEs have key roles in the pathogenesis of diabetic complications.
      Two discoveries have advanced our knowledge of the roles of RAGE in inflammation.
      First, this receptor has multiple ligands and binds not only AGEs but also
      proinflammatory, calcium-binding S100 proteins (also known as calgranulins) and
      nuclear high mobility group protein box-1. Second, RAGE is expressed on T
      lymphocytes, monocytes and macrophages; RAGE expression on T lymphocytes is
      essential for effective priming of immune responses in vivo. In this Review, we
      chronicle roles for RAGE in the pathogenesis of diabetic complications and
      develop the hypothesis that, in addition to RAGE's central role in the
      inflammatory response, it is critically linked to the pathogenesis of types 1 and
      2 diabetes.

PMID- 18332898
TI  - DRD4 48 bp VNTR but not 5-HT 2C Cys23Ser receptor polymorphism is related to
      antipsychotic-induced weight gain.
AB  - Weight gain is a major side effect of antipsychotic treatment. The
      antidopaminergic and antiserotonergic effect of antipsychotics may contribute to
      antipsychotic-induced weight gain. We, therefore conducted a prospective clinical
      study, to investigate whether the D4 receptor (DRD4) 48 bp (base pair) variable
      number of tandem repeat (VNTR) polymorphism and the 5-hydroxytryptamine 2C
      receptor (HT(2C)) cysteine for serine substitution at position 23 (Cys23Ser)
      polymorphism may influence weight gain during antipsychotic treatment in a
      naturalistic setting of 102 Caucasian psychiatric in-patients. Patients suffering
      from psychotic disorders and treated according to local clinical practice were
      classified as either homozygous for the shorter alleles of the DRD4 48 bp VNTR
      polymorphism (<7-fold repeat, group 1) or heterozygous/homozygous for the long
      allele (7-fold repeat or higher, group 2). HT(2C) Cys23Ser polymorphism male
      patients were grouped hemizygous G (Cys) or C (Ser), while female patients were
      GG, GC or CC and both sexes were evaluated separately. Concerning the DRD4 48 bp
      VNTR polymorphism the increase in body mass index was significantly less in group
      1 (0.38 kg m(-2); s.d.=1.04) than in group 2 (0.89 kg m(-2); s.d.=1.23; P=0.003).
      The difference between the genotype groups remained significant in male patients
      but not in female patients. In contrast, no influence on antipsychotic-induced
      increase in body weight was observed for the HT(2C) Cys23Ser polymorphism. These
      results support the hypothesis that the DRD4 48 bp VNTR polymorphism influences
      antipsychotic-induced weight gain. Male patients may be more affected than female
      patients. Due to the limitations of the study (heterogeneity of treatment,
      pretreatment and concomitant therapy) further studies are required before
      diagnostic genotyping of the DRD4 48 bp VNTR polymorphism may be useful for
      individualizing therapy.

PMID- 18332899
TI  - Pharmacogenetics of hypersensitivity to abacavir: from PGx hypothesis to
      confirmation to clinical utility.
AB  - The hypersensitivity (HSR) to abacavir (ABC) pharmacogenetics (PGx) program
      represents the progression from an exploratory discovery to a validated
      biomarker. Within the program, two retrospective PGx studies were conducted to
      identify HIV-1 patients at increased risk for ABC HSR, a treatment-limiting and
      potentially life-threatening adverse event. A strong statistical association
      between the major histocompatibility complex allele, HLA-B*5701, and clinically
      diagnosed ABC HSR was identified but varied between racial populations.
      Subsequently, ABC skin patch testing was introduced as a research tool to
      supplement clinical case ascertainment. In a randomized, prospective study
      evaluating the clinical utility of HLA-B*5701 screening, avoidance of ABC in HLA
      B*5701-positive patients significantly reduced clinically diagnosed ABC HSR and
      eliminated patch test-positive ABC HSR. Finally, a retrospective PGx study
      supports the generalizability of the association across races. Prospective HLA
      B*5701 screening should greatly reduce the incidence of ABC HSR by identifying
      patients at high risk for ABC HSR before they are treated.

PMID- 18332900
TI  - Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in
      patients with prolactin-secreting pituitary adenomas.
AB  - Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor
      size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding
      type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB
      remain largely unknown. To assess the association of DRD2 with sensitivity to CB,
      TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a
      cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2
      alleles frequencies did not differ between patients and 212 healthy subjects.
      Conversely, NcoI-T allele frequency was higher in resistant rather than
      responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038)
      and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T
      /NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with < or =3
      mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB
      was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that
      this variant may lead to reduction and instability of DRD2 mRNA or protein.

PMID- 18332901
TI  - Prognostic significance of disordered calcium metabolism in hormone-refractory
      prostate cancer patients with metastatic bone disease.
AB  - Bone metabolic disruption that occurs in bone metastatic prostate cancer could
      lead to disturbances of calcium metabolism. The prognostic role of either
      hypocalcemia or hypercalcemia was assessed in a consecutive series of hormone
      refractory bone metastatic prostate cancer patients. Serum calcium was measured
      in 192 patients. The presence of hypocalcemia and hypercalcemia was related with
      baseline biochemical and clinical characteristics and the role of these two
      calcium disturbances in predicting prognosis and adverse skeletal-related events
      (SREs) was assessed. As compared to normocalcemic patients, hypocalcemic patients
      (n=51) had higher tumor load in bone (P=0.005), higher plasma chromogranin A
      (CgA, P=0.01), serum alkaline phosphatase (P=0.01), urinary N-telopeptide (NTX,
      P=0.002) and lower hemoglobin values (P=0.01), while hypercalcemic patients
      (n=16) had higher plasma CgA (P=0.001) and serum lactate dehydrogenase values
      (P=0.001), higher bone pain (P=0.003) and a lower frequency of pure osteoblastic
      lesions (P=0.001). Hypercalcemia was significantly associated with poor
      prognosis: hazard ratio (HR), 1.9 (95% confidence Interval (CI) 1.2-3.3) and
      higher risk to develop SREs HR, 2.5 (95% CI 1.2-5.2, P=0.01), while hypocalcemia
      was not associated with poor prognosis. The prognostic role of hypercalcemia was
      maintained in multivariate analysis after adjusting for validated prognostic
      parameters: HR, 2.72 (95% CI 1.1-6.8, P=0.03). These data suggest that serum
      calcium levels should be taken into account in the clinical decision-making
      process of bone metastatic prostate cancer patients. Patients with asymptomatic
      hypercalcemia could benefit of a strict follow-up and an immediate bisphosphonate
      treatment. Further prospective clinical trials are needed to confirm this
      finding.

PMID- 18332902
TI  - Should liver transplantation be excluded in elderly patients?

PMID- 18332903
TI  - Detection of an aortoenteric fistula in a patient with intermittent bleeding.
AB  - BACKGROUND: A 57-year-old male with an aortobifemoral bypass graft presented to a
      gastroenterology clinic with a 3-month history of intermittent hematemesis,
      melena and fever. The patient had received antibiotic therapy 2 months before for
      the same symptoms; however, following brief regression ( approximately 3 weeks)
      the symptoms had returned. INVESTIGATIONS: Physical examination; analysis of full
      blood count; measurement of erythrocyte sedimentation rate, C-reactive protein
      levels, liver enzymes, electrolytes, renal function, serum cholesterol and serum
      triglyceride; HIV serology; blood, sputum, urine and stool culture analysis;
      performance of esophagogastroduodenoscopy, colonoscopy, abdominal ultrasonography
      and multidetector CT scanning. DIAGNOSIS: Aortoenteric fistula with an
      inflammatory mass surrounding the aortobifemoral bypass graft. MANAGEMENT:
      Laparotomy with removal of the aortobifemoral bypass graft, performance of an
      extra-anatomic right axillofemoral bypass graft and an extra-anatomic right-left
      femorofemoral bypass graft.

PMID- 18332904
TI  - Is kinase activity essential for biological functions of BRI1?
AB  - Brassinosteroids (BRs) are a major group of plant hormones that regulate plant
      growth and development. BRI1, a protein localized to the plasma membrane,
      functions as a BR receptor and it has been proposed that its kinase activity has
      an essential role in BR-regulated plant growth and development. Here we report
      the isolation and molecular characterization of a new allele of bri1, bri1-301,
      which shows moderate morphological phenotypes and a reduced response to BRs under
      normal growth conditions. Sequence analysis identified a two-base alteration from
      GG to AT, resulting in a conversion of 989G to 989I in the BRI1 kinase domain. An
      in vitro assay of kinase activity showed that bri1-301 has no detectable
      autophosphorylation activity or phosphorylation activity towards the BRI1
      substrates TTL and BAK1. Furthermore, our results suggest that bri1-301, even
      with extremely impaired kinase activity, still retains partial function in
      regulating plant growth and development, which raises the question of whether
      BRI1 kinase activity is essential for BR-mediated growth and development in
      higher plants.

PMID- 18332905
TI  - AtTHIC, a gene involved in thiamine biosynthesis in Arabidopsis thaliana.
AB  - Thiamine (vitamin B(1)) is an essential compound for organisms. It contains a
      pyrimidine ring structure and a thiazole ring structure. These two moieties of
      thiamine are synthesized independently and then coupled together. Here we report
      the molecular characterization of AtTHIC, which is involved in thiamine
      biosynthesis in Arabidopsis. AtTHIC is similar to Escherichia coli ThiC, which is
      involved in pyrimidine biosynthesis in prokaryotes. Heterologous expression of
      AtTHIC could functionally complement the thiC knock-out mutant of E. coli.
      Downregulation of AtTHIC expression by T-DNA insertion at its promoter region
      resulted in a drastic reduction of thiamine content in plants and the knock-down
      mutant thic1 showed albino (white leaves) and lethal phenotypes under the normal
      culture conditions. The thic1 mutant could be rescued by supplementation of
      thiamine and its defect functions could be complemented by expression of AtTHIC
      cDNA. Transient expression analysis revealed that the AtTHIC protein targets
      plastids and chloroplasts. AtTHIC was strongly expressed in leaves, flowers and
      siliques and the transcription of AtTHIC was downregulated by extrinsic thiamine.
      In conclusion, AtTHIC is a gene involved in pyrimidine synthesis in the thiamine
      biosynthesis pathway of Arabidopsis, and our results provide some new clues for
      elucidating the pathway of thiamine biosynthesis in plants.

PMID- 18332906
TI  - Successful bone marrow transplantation in a girl with Fanconi anemia and
      preterminal renal failure.

PMID- 18332907
TI  - Consulting clinic for related family donors in hematopoietic stem cell
      transplantation.

PMID- 18332908
TI  - The relationship between absolute lymphocyte count with PFS in patients with
      Hodgkin's lymphoma undergoing autologous hematopoietic cell transplant.
AB  - Previous reports in Hodgkin's lymphoma (HL) patients undergoing autologous
      hematopoietic cell transplantation (AHCT) have demonstrated a significant
      association between the absolute lymphocyte count at day 15 (ALC-15) with
      survival. To evaluate this finding further, we analyzed 146 patients with
      relapsed/refractory HL who underwent AHCT to evaluate the relationship between
      lymphocyte counts at apheresis and at two time points (days 15 and 90) after AHCT
      with PFS. We found no association between the ALC-15 and the ALC-90 with PFS. We
      found lymphocyte counts at apheresis and disease sensitive to salvage
      chemotherapy were predictive of PFS. In conclusion, our study does provide some
      support for the theory that the immune system may be important in disease control
      but further and more detailed studies in this area are required.

PMID- 18332909
TI  - Early identification and management of graft failure after unrelated cord blood
      transplantation.
AB  - Delayed hematologic recovery is common after unrelated donor umbilical cord blood
      transplants (UCBT). Clinically it is important to quickly differentiate slow
      engraftment from graft failure (GF). We report the engraftment data on 110
      pediatric UCBT recipients. By day 28, 71 patients achieved an ANC >0.5 x 10(9)
      per liter, and 6 others died early without recovery. Of the remaining 33 patients
      who were still neutropenic, 20 eventually attained donor myeloid recovery, 3 died
      of transplant-related complications or recurrent leukemia and 10 survived without
      donor-derived hematopoiesis. These patients received a second UCBT 33-95 days
      after the first transplant, after additional immunosuppression. One patient died
      early, the remaining nine patients were engrafted; eight demonstrated complete,
      and one mixed, donor chimerism (with subsequent graft loss). Acute GVHD developed
      in three, and chronic GVHD in six of the eight engrafted patients. Two patients
      developed EBV-lymphoproliferative disorder. Infections, especially viral, were
      common and protracted. Six of 10 patients are alive, 165-1375 (median 1147) days
      after second UCBT. Chimerism studies correlated with subsequent engraftment
      course. Any result showing <5% donor cells was associated with irreversible graft
      loss. In conclusion, early second UCBT after primary GF is a feasible treatment
      option. Chronic GVHD and viral reactivation are common post transplant.

PMID- 18332910
TI  - Graft-versus-adult T-cell leukemia/lymphoma effect following allogeneic
      hematopoietic stem cell transplantation.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has proven
      effective in adult T-cell leukemia/lymphoma (ATL) patients. To study the graft
      versus-ATL (Gv-ATL) effects after allo-HSCT, we analyzed 21 ATL patients who had
      been treated at our hospital. Of these, 18 had acute-, 2 had lymphoma- and 1 had
      chronic-type ATL; at allo-HSCT, seven patients were in CR, one was in PR, five
      had stable disease (SD) and eight had progressive disease (PD). Disease state
      after allo-HSCT was CR in 14, PR in 3, SD in 1 and PD in 3 patients. Among 15
      patients who survived longer than 100 days, ATL relapsed in 10 patients, skin
      relapsed in 9 patients and 5 had relapsed on the skin alone. After we
      discontinued immunosuppressant therapy in these 10 patients, 8 manifested GVHD;
      ATL was ameliorated to CR in 6 patients. Donor lymphocytes were infused into two
      patients who did not show GVHD; one obtained CR. In five patients with skin
      relapse alone, four patients achieved CR following the discontinuation of the
      immunosuppressants. Our results demonstrate that relapse of ATL after allo-HSCT
      tends to develop on skin, and Gv-ATL effects played a critical role in the
      outcome of allo-HSCT for ATL.

PMID- 18332911
TI  - Alpha 4-integrin-positive microvesicles and SDF-1 in peripheral blood stem cell
      harvest.

PMID- 18332912
TI  - Cell cycle and immune-related processes are significantly altered in chronic
      GVHD.
AB  - Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the
      molecular characteristics underlying chronic GVHD, we analyzed the gene
      expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic
      stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering
      showed that the entire expression profiles of chronic GVHD samples were clearly
      different from those of the non-GVHD samples, and significance analysis of
      microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D,
      were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD
      patients. Gene ontology annotation revealed that these genes are related to the
      phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase
      chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1
      and CD3D in separate samples. Pathway-wise global test revealed that differential
      gene expression in cell cycle and T cell immune-associated pathways were
      significant between GVHD patients and non-GVHD patients. Seventeen classifier
      genes selected using a PAM (prediction analysis of microarray) algorithm showed
      favorable performance (prediction accuracy=0.85) for identifying patients with
      chronic GVHD. In conclusion, we identified differentially expressed genes and
      pathways in chronic GVHD patients using microarray analysis, and we also selected
      diagnostic genes predicting chronic GVHD status.

PMID- 18332913
TI  - Induction of recipient cell-specific donor T-cell anergy by UV-C-irradiated
      recipient immature monocyte-derived dendritic cells.
AB  - The induction of donor T-cell anergy to recipient cells for reducing GVHD could
      be one way of expanding donor candidates for HLA-mismatched hematopoietic SCT.
      The present study was designed to clarify whether recipient cell-specific T-cell
      anergy could be induced by priming donor lymphocytes with recipient monocyte
      derived DCs (mo-DCs) irradiated with ultraviolet-C (UV-C). By irradiation of mo
      DCs with UV-C, the expression of DC-associated surface phenotypes such as CD83,
      CD80, CD86 and CD40 was reduced and the antigen-presenting ability of UV-C
      irradiated mo-DCs was clearly decreased. By co-culturing normal donor 1
      lymphocytes with UV-C-irradiated donor 2 immature mo-DCs, the response of the
      lymphocytes to donor 2 mature mo-DCs was markedly reduced as compared with that
      of the lymphocytes prestimulated with non-irradiated donor 2 immature mo-DCs or
      UV-C-irradiated mo-DCs derived from a different individual donor 3. The present
      study demonstrated that recipient cell-specific T-cell anergy could be induced by
      priming donor lymphocytes with UV-C-irradiated recipient immature mo-DCs in
      hematopoietic SCT. These data suggest the applicability of donor graft cells,
      which have been prestimulated with UV-C-irradiated recipient immature mo-DCs, for
      expanding donor candidates in HLA-mismatched hematopoietic SCT.

PMID- 18332914
TI  - Segregated graft-versus-tumor effect between CNS and non-CNS lesions of Ewing's
      sarcoma family of tumors.

PMID- 18332915
TI  - Impact of pretransplant therapy in patients with newly diagnosed myeloma
      undergoing autologous SCT.
AB  - Autologous SCT (ASCT) remains an effective therapy for eligible patients with
      myeloma. Previous studies have suggested a lack of impact of the initial therapy
      on the outcome after ASCT. It is not clear if incorporation of new agents in the
      initial treatment regimens will have any impact on the outcome after ASCT. We
      studied 472 patients undergoing ASCT within 12 months of diagnosis to assess the
      effect of initial therapy on the outcome after ASCT. Patients received initial
      therapy with vincristine, adriamycin and dexamethasone (VAD), dexamethasone,
      thalidomide and dexamethasone or lenalidomide and dexamethasone. While patients
      treated with dexamethasone alone had higher disease burden at ASCT, no
      differences were observed in the response rates to ASCT, post transplant
      complications or treatment-related mortality among the groups. The median time to
      progression after ASCT was 27.1, 24.7, 21.1 months and did not reach the VAD,
      Dex, Thal-Dex and Len-Dex group, respectively, P=0.11. The median overall
      survival from ASCT was 62 months for VAD, 69.6 months for Dex and were not
      reached for Thal-Dex and Len-Dex groups, P=0.2. For patients undergoing early
      ASCT for myeloma, the nature of initial treatment utilized has no long-term
      impact on the outcome of ASCT.

PMID- 18332916
TI  - Effect of laser irradiation on silica substrate contaminated by aluminum
      particles.
AB  - A major issue in the use of high-power lasers, such as the Laser Megajoule (LMJ),
      is laser-induced damage of optical components. One potential damage initiator is
      particulate contamination, but its effect is hard to distinguish from that of
      other damage precursors. To do so, we introduced artificial contaminants typical
      of metallic pollution likely to be present on the optical components of the LMJ
      chains. More precisely, aluminum particles of two different sizes were placed on
      a silica sample. These dots were characterized by optical microscopy and
      profilometry. Then they were exposed to a laser beam with a pulse length of 6.5
      ns at 1064 nm and fluences in the range from 1 to 40 J/cm(2). Each dot was
      characterized again with the same techniques and also by photothermal microscopy.
      To complete the experimental results, we performed numerical simulations with a
      one-dimensional Lagrangian hydrodynamics code. We show that the particle removal
      by laser irradiation produces a modification of the silica surface that does not
      evolve into catastrophic damage under subsequent irradiation. However, the effect
      does depend on the size of the dots. We demonstrate that a procedure exists that
      removes the dot and leaves the site capable of resisting high fluence.

PMID- 18332917
TI  - The association between higher volume and better outcome for
      pancreatoduodenectomy.

PMID- 18332918
TI  - 'Cross-section gastroenterostomy' in patients with irresectable periampullary
      carcinoma.
AB  - BACKGROUND: The most frequent complication following gastroenterostomy (GE) for
      gastric outlet obstruction is delayed gastric emptying (DGE), which occurs in
      roughly 20% of patients. There is evidence that DGE may be linked to the
      longitudinal incision of the jejunum and that a transverse incision (cross
      section GE) may decrease the incidence of DGE following GE. PATIENTS AND METHODS:
      In contrast to the orthodox GE, the jejunum is severed transversely up to a
      margin of 1.5 cm at the mesenteric border and the anastomosis is created with a
      single running suture. A Braun anastomosis is added 20-30 cm distally to the GE.
      Patients were followed prospectively with special regard to the occurrence of
      DGE. RESULTS: Between 1 August 1994 and 1 August 1998, 25 patients underwent
      cross-section GE, mostly because of an irresectable periampullary carcinoma.
      Eight patients exhibited clinical signs of gastric outlet obstruction
      preoperatively, while in 17 the GE was performed on a prophylactic basis. A
      biliary bypass was added in 15 patients. There was no disruption of the GE, but
      one patient died in hospital (4%). The nasogastric tube was withdrawn on the
      first postoperative day (range 0-6 days), a liquid diet was started on the fifth
      day (range 2-7 days) and a full regular diet was tolerated at a median of 9 days
      (6-14 days).The incidence of DGE was 4%: only the single patient who died
      fulfilled the formal criteria for DGE. DISCUSSION: In contrast to orthodox GE,
      DGE seems to be of minor clinical importance following cross-section GE. As the
      technique is easy to perform, is free of specific complications and leads to a
      low incidence of DGE, it should be considered as an alternative to conventional
      GE.

PMID- 18332919
TI  - Minimally invasive management of bile leak after laparoscopic cholecystectomy.
AB  - BACKGROUND: Bile leakage is an uncommon complication of cholecystectomy.The bile
      may originate from the gallbladder bed, the cystic duct or rarely from injury to
      a major bile duct.This study aims to evaluate the efficacy of minimal access
      endoscopic and percutaneous techniques in treating symptomatic bile leak.
      PATIENTS AND METHODS: Twenty-one patients with symptomatic bile leak following
      laparoscopic cholecystectomy underwent assessment of the extent of the bile leak
      via ultrasound/CT and ERCP. Following diagnosis, the patients were treated by
      sphincterotomy and biliary drainage and, if necessary, percutaneous drainage of
      the bile collection. RESULTS: Only one patient required primary surgical
      treatment following diagnosis of a major duct injury.The other 20 were treated by
      a combination of sphincterotomy (including a stent in most) plus percutaneous
      drainage in six. In 19 of 20, this minimal access approach stopped the leak.
      DISCUSSION: Most patients who present with bile leakage after cholecystectomy can
      be managed successfully by means of ERCP with percutaneous drainage of any large
      bile collection.

PMID- 18332920
TI  - Hypotension during ERCP is common but not a risk factor for post-ERCP
      pancreatitis.
AB  - BACKGROUND: In patients undergoing cardiopulmonary bypass, hypotension is a risk
      factor for developing acute pancreatitis. Hypotension in animal models can also
      induce pancreatitis. We sought to determine whether or not relative hypotension
      during ERCP is a risk factor for developing acute pancreatitis. PATIENTS AND
      METHODS: A nested, case-control study reviewed all cases of post-ERCP
      pancreatitis resulting from ERCPs performed at this institution between May 1993
      and May 1998. Post-ERCP pancreatitis was defined as abdominal pain requiring
      hospitalisation and elevation of serum amylase or lipase more than four times the
      upper limit of normal 24 hours or more after ERCP. Non-invasive blood pressure
      measurements were recorded automatically at least every 5 min during ERCP.
      Hypotension was defined as any systolic blood pressure (SBP) <100 mmHg, diastolic
      blood pressure (DBP) <60 mmHg, or mean blood pressure (MBP) <80 mmHg. Controls
      were chosen randomly from ERCPs performed on the same or the nearest day as each
      index case. RESULTS: In total, 1854 ERCPs were reviewed from the study
      period.There were 96 cases of post-ERCP pancreatitis,giving an incidence of 5.2%.
      The average age of cases was 48 years, while that of controls was 55 years (p <
      0.003).There were no differences between the groups regarding gender, ERCP
      findings, need for sphincterotomy nor acinar filling on the pancreatogram
      (acinarisation). At least one episode of hypotension was recorded in 32% of cases
      and 30% of controls (p = 0.75). There were no differences between cases and
      controls comparing mean pre- and intra-procedure SBP, DBP and MBPs, or lowest
      procedure SBP, DBP and MBP. DISCUSSION: Episodes of acute hypotension are common
      during ERCP but are not a risk factor for developing post-ERCP pancreatitis.

PMID- 18332921
TI  - Leiomyosarcoma of the pancreas.
AB  - BACKGROUND: This is a single case report of a rare tumour, pancreatic
      leiomyosarcoma. CASE OUTLINE: A 44-year-old woman presented with a painless
      epigastric mass, and CT scan showed a cystic lesion of the head of pancreas. An
      associated epigastric mass was found to be a lipoma. Pancreatoduodenectomy was
      successfully performed. Pathology revealed leiomyosarcoma of the pancreas. The
      patient is well and free of disease four years later. DISCUSSION: Leiomyosarcomas
      of the pancreas can present with abdominal pain, weight loss and abdominal mass.
      However, a certain number of tumours will be discovered incidentally and may be
      cystic in nature. This patient had no antecedent history of gallstones or alcohol
      and underwent a curative resection.

PMID- 18332922
TI  - Benign inflammatory pseudotumour of the biliary tract masquerading as a Klatskin
      tumour.
AB  - BACKGROUND: In the presence of obstructive jaundice, irregular strictures high in
      the common hepatic duct are usually due to bile duct cancer or to metastatic
      infiltration from other malignant tumours. Postoperative strictures and a variety
      of benign tumours also occur in this region but usually have a distinctive
      appearance on retrograde cholangiography. Obstruction of the bile duct due to an
      impacted calculus in Hartmann's pouch (Mirizzi syndrome) and sclerosing
      cholangitis also have characteristic radiological appearances and are supported
      by the coexistence of gallstones and inflammatory bowel disease respectively.
      CASE OUTLINE: This case report describes a much rarer entity, an inflammatory
      pseudotumour of the bile duct, which was only diagnosed after histological
      evaluation of a specimen resected for presumed bile duct cancer. DISCUSSION:
      Clinicians should be aware of the possibility of a benign cause for a
      cholangiogram showing obstruction due to an apparent Klatskin tumour and of the
      good long-term outcome of surgical excision of these lesions.

PMID- 18332923
TI  - Cystadenoma of the liver without mesenchymal stroma in a female following
      hormonal therapy for acne.
AB  - BACKGROUND: Liver cystadenomas are relatively rare tumours that can be difficult
      to diagnose; treatment entails complete surgical extirpation either by either
      anatomical resection or enucleation. CASE OUTLINE: A 19-year-old woman presented
      with acute onset of abdominal pain and was found to have a multilocular giant
      liver cyst.The cyst was percutaneously drained; CEA and CA 19-9 tumour markers
      were elevated in this cyst fluid: CEA 96 microg/L, CAI9-9 37 550 kU/L. The cyst
      was completely enucleated and has not recurred. Pathological examination
      confirmed a cystadenoma without mesenchymal stroma, and tumour oestrogen and
      progesterone receptors were negative. DISCUSSION: This is the fourth report of a
      liver cystadenoma without mesenchymal stroma in a female and the first to
      document elevated cyst fluid tumour markers. This case also illustrates the
      possible relationship between hormonal therapy and tumour growth.

PMID- 18332924
TI  - Hepatic outflow occlusion in laparoscopic hepatectomy.
AB  - BACKGROUND: The application of laparoscopic techniques to major hepatic resection
      has been limited by the risk of hepatic vein laceration leading to massive
      bleeding or gas embolism. A balloon catheter has therefore been designed to
      occlude hepatic vein flow during experimental laparoscopic hepatectomy. METHODS:
      The procedure was attempted in 8 pigs weighing around 50 kg and submitted to
      laparoscopic left hemihepatectomy. A specially designed balloon catheter was
      inserted via the femoral vein and advanced into the retrohepatic segment of
      inferior vena cava (IVC). After inflation of the balloon with 17 ml contrast,
      angiography confirmed complete occlusion of this segment, while a central rigid
      channel allowed passage of blood from IVC to right atrium. Haemodynamic studies
      were performed during resection of the left and left paramedial lobes of the
      liver, which was completed laparoscopically using ultrasonic coagulating shears
      and vascular linear staplers. RESULTS: Inflation of the balloon reduced mean
      arterial pressure to 75-79% and central venous pressure to 29-42% of baseline
      values, while cardiac output also fell (to 69-73% of basal). IVC blood flow
      decreased to 58% and hepatic venous flow to only 16% of pre-inflation values.
      Left hemihepatectomy was successfully achieved by the laparoscopic route in all 8
      animals with a mean balloon inflation time of 30 min and blood loss of 166 ml.
      Haemodynamic indices returned to normal after deflation of the balloon at the end
      of the resection. DISCUSSION: This preliminary study shows that hepatic venous
      outflow can be occluded by this special balloon catheter and that animals can
      tolerate the associated haemodynamic disturbance. Similar techniques in man might
      permit major hepatectomy to be safely achieved by a laparoscopic approach.

PMID- 18332925
TI  - Pancreatic transplantation for patients with Type I diabetes.

PMID- 18332926
TI  - Recurrent bile duct stones after transduodenal sphincteroplasty.
AB  - BACKGROUND: Transduodenal sphincteroplasty (TDS) offers permanent prophylaxis
      against further stones in the common bile duct (CBD) by allowing continuous free
      efflux of bile from the papilla. PATIENTS AND RESULTS: In a personal series of
      267 consecutive operations, four patients underwent further treatment for
      recurrent CBD stones during a median follow-up of 12 years. Three of them
      received Roux-en-Y biliary diversion and had no further symptoms; the fourth
      patient remains well four years after endoscopic extraction of stones.
      DISCUSSION: Recurrent stone formation is rare after an adequate TDS and probably
      reflects retained food debris within the CBD. Initial treatment may be
      endoscopic, but biliary diversion is needed for those with recurrent symptoms.

PMID- 18332927
TI  - Effect of granulocyte-macrophage colony-stimulating factor on hepatic
      regeneration after 70% hepatectomy in normal and cirrhotic rats.
AB  - BACKGROUND: Post-hepatectomy liver insufficiency is one of the most serious
      postoperative problems and its prevention is important after major hepatic
      resection, especially in the cirrhotic liver. Some growth factors and cytokines
      appear to play important roles in liver regeneration. In the present study we
      have investigated the effects of granulocyte-macrophage colony-stimulating factor
      (GM-CSF) on hepatic regeneration after 70% partial hepatectomy (PH) in cirrhotic
      and non-cirrhotic rats. METHODS: A rat model of liver cirrhosis was prepared
      using thioacetamide (TAA) (a dose of 20 mg/100 g body w, intra-peritoneally) on
      three days a week for 12 weeks. Adult male rats were divided into four
      groups:Group 1 (n=10) no cirrhosis and no GM-CSF; Group 2 (n=10) no cirrhosis and
      GM-CSF; Group 3 (n=10) cirrhosis and no GM-CSF; and Group 4 (n=10) cirrhosis and
      GM-CSF. All the rats underwent a 70% hepatectomy, and GM-CSF was administrated
      immediately after operation in Groups 2 and 4. On postoperative days 2 and 7,
      fresh samples from the remnant liver were obtained to evaluate its regenerative
      capacity.The liver regenerative process was estimated by DNA synthesis, using
      flow cytometry. RESULTS: Proliferation index (PI) of hepatocytes at 48 h was
      higher in Group 4 rats than Group 3 rats (p<0.05). On postoperative day 7, PI was
      elevated in Group 3 rats compared with Group 4 rats, but this difference was not
      statistically significant. In non-cirrhotic rats given GM-CSF, PI was increased
      compared with Group 1 rats at day 2 (p<0.05), but not at day 7. CONCLUSIONS: The
      findings suggest that the proliferative capacity of liver cells is impaired and
      delayed after 70% PH in cirrhotic rat liver. GM-CSF administration might enhance
      the liver PI in both normal and TAA-induced cirrhotic rats.

PMID- 18332928
TI  - Telomerase activity, P53 mutation and Ki-ras codon 12 point mutation of the
      peripheral blood in patients with hepato pancreato biliary diseases.
AB  - BACKGROUND: With progress in molecular biology, the presence of telomerase
      activity, P53 mutation and Ki-ras codon 12 point mutation has been reported in
      malignant tumours of the liver, pancreas and biliary tree. The purpose of this
      paper is to clarify the clinical implications of finding these three biomarkers
      in the peripheral blood of affected patients. METHODS: Telomerase activity, P53
      mutation, and Ki-ras codon 12 point mutation in the peripheral blood were
      examined among 86 patients with hepato pancreato biliary disease, both benign and
      malignant, and the results were compared with clinical findings. RESULTS: Of 20
      patients with benign conditions, only one patient with intraductal papillary
      adenoma showing severe dysplasia exhibited a biomarker (telomerase activity) in
      the peripheral blood. In total, there were 66 patients with various HPB
      carcinomas. Of 56 cancer patients studied pre-operatively, 16 were positive for
      more than one biomarker, 13 were positive for telomerase activity, 4 for P53
      mutation (three at exon 7 and another at exon 8), and 2 for Kiras codon 12 point
      mutation (both in the second letter). Twelve of the 16 biomarker-positive
      patients had stage IV disease as opposed to 23 of 40 biomarker-negative patients.
      The resectability rate of the cancer was 38% in positive patients and 50% in
      negative patients. The one-year survival rate after resection was zero in
      positive patients and 15% in negative patients, but the difference was not
      significant (P=0.65). Of 32 patients with liver metastasis at the time of the
      molecular examination, eight were positive and 24 negative. Of 34 patients
      without liver metastasis, nine were positive and 25 negative. The development of
      subsequent liver metastases in those without them at the start was not
      significantly different in those with and without biomarkers (56 vs 36%: P=0.31).
      CONCLUSIONS: The three novel biomarkers of the peripheral blood seemed to be of
      little value for screening of early malignant HPB neoplasms but may help to
      predict liver metastasis.

PMID- 18332929
TI  - Vascular-enteric fistulas associated with radiation therapy in patients with
      pancreatic adenocarcinoma.
AB  - BACKGROUND: Irradiation therapy is being evaluated widely as an adjunct to
      therapy of resectable and unresectable pancreatic exocrine carcinoma.
      Exsanguinating haemorrhage has been an occasional late complication. CASE
      OUTLINES: Two patients with unresectable cancer of the pancreas were treated by
      bypass, chemotherapy and both intra-operative and postoperative irradiation. Both
      patients died 5-11 months later of gastroduodenal haemorrhage from arterio
      enteric fistulas, which were confirmed by autopsy but had been uncontrolled by
      selective embolisation. A third patient, for whom little other information was
      available, died of upper abdominal haemorrhage 5 months after a 'curative'
      resection combined with intra-operative and postoperative irradiation.
      DISCUSSION: Judgement in management is difficult because of the poor prognosis
      from the underlying disease on the one hand versus the fact that site of bleeding
      has sometimes been from complicating benign disease. Better endovascular
      techniques of control of such haemorrhage may be developing.

PMID- 18332930
TI  - Acinar cell carcinoma of the pancreas with and without endocrine differentiation.
AB  - BACKGROUND: Acinar cell carcinoma (ACC) is a rare pancreatic neoplasm,
      representing 1% of exocrine tumours and containing a variable endocrine
      component. Three recent cases of ACC are reported. CASE OUTLINES: A 72-year-old
      man with painless obstructive jaundice had a 5-cm mass in the head of pancreas
      resected by Whipple's operation; histopathological examination showed a typical
      ACC. A 33-year-old man with weight loss and abnormal liver function had a dilated
      biliary tree but no mass on imaging. Pylorus-preserving pancreatoduodenectomy was
      performed, and histology showed a mixed acinar-neuro-endocrine tumour. A 56-year
      old man with weight loss and a palpable mass had a 15-cm mass in the distal body
      of pancreas, which was resected en bloc with the spleen and adherent stomach; it
      was a cystic ACC. RESULTS: Two patients are alive and free of disease at 30
      months and 15 months, while the third patient with locally advanced disease died
      of myocardial infarction at 9 weeks. DISCUSSION: Acinar structures are the
      hallmark of this neoplasm, which carries a better survival rate than ductal
      cancer. Surgical excision prolongs survival and offers the best chance of cure.

PMID- 18332931
TI  - Hepatocellular carcinoma secondary to cholecystectomy: a one in a million chance.
AB  - BACKGROUND: Cholecystectomy is a common procedure and its complications are well
      documented. CASE OUTLINE: A 63-year-old female sustained a bile duct injury
      during cholecystectomy requiring choledochoduodenostomy. She subsequently
      developed secondary biliary cirrhosis and ultimately required orthotopic liver
      transplantation. A focus of hepatocellular carcinoma was discovered within her
      liver. DISCUSSION: This case represents the first documented case of
      hepatocellular carcinoma as a late complication of cholecystectomy. The risk of
      this occurring can be estimated at 1:1,140,000 (range 1:11,000 to 1:120,000,000).

PMID- 18332932
TI  - Bloodless hepatectomy technique.
AB  - BACKGROUND: Surgical resection remains the gold standard in dealing with liver
      tumours. Blood loss, biliary leak and postoperative liver function are still the
      main concerns of surgeons operating on the liver, even though different
      techniques have been developed to allow safer liver resection. A novel concept
      for liver resection is described using a radiofrequency energy (RF) assisted
      technique. METHOD: A patient with a large colorectal liver metastasis located in
      segments VI, VII, VIII underwent a right hepatectomy using this technique. At
      laparotomy the tumour was staged with intraoperative ultrasonography, and a
      'cooled tipped' radiofrequency probe was used to achieve a 'zone of desiccation'
      in the liver parenchyma 2 cm away from the edge of the tumour. Liver parenchyma
      was subsequently divided with a surgical scalpel. RESULTS: The resection time was
      80 min with a blood loss of 30 ml. The patient was discharged on the ninth
      postoperative day without complications. DISCUSSION: Liver resection assisted by
      RF energy is feasible and safe. This technique could offer a new method for
      'transfusion-free' resection without the need for sutures, ties, staples, tissue
      glue or admission to the intensive care unit.

PMID- 18332933
TI  - The Brisbane 2000 terminology of liver anatomy and resections. HPB 2000; 2:333
      39.

PMID- 18332934
TI  - Extended resection for pancreatic adenocarcinoma.

PMID- 18332935
TI  - Handling of biliary complications following laparoscopic cholecystectomy in the
      setting of Tripoli Central Hospital.
AB  - BACKGROUND: Laparoscopic cholecystectomy (LC) has an increased incidence of bile
      duct injury and bile leak when compared with open cholecystectomy. This study
      reviews management of these complications in a general hospital setting. Data
      collected from patients diagnosed and treated in one surgical unit for biliary
      complications after LC between 1992 and 1996 were analysed. METHOD: A total of 14
      patients were examined. Diagnosis was defined mainly by Endoscopic retrograde
      cholangiopancreatography (ERCP) and undetected choledocholithiasis was discovered
      in association with two of these complications. 43% of patients presented after
      LC with early postoperative bile leak or jaundice due to partial or complete bile
      duct excision or slippage of clips from the cystic duct. 57% presented with late
      biliary strictures. Thirteen patients were treated surgically, with biliary
      reconstruction (11 patients), direct repair (one) and cystic duct ligation in
      combination with clearance of bile duct from large multiple stones (one). One
      patient,who had clip displacement from cystic duct in combination with misplaced
      clip on right hepatic duct, was treated elsewhere. Postoperatively, one patient
      developed anastomotic leak and another died from sequelae of bile duct
      transection requiring staged operations. CONCLUSIONS: It is concluded that, in an
      environment similar to that where the authors had to work, LC should be performed
      in hospitals with facility to perform ERCP or when access for this technique is
      available in a nearby institution. Early recognition and immediate management of
      biliary injuries is dependent on individual resources and circumstances but, if
      required, consultation with colleagues or referral of patients with suspected or
      established biliary complications should not be delayed.

PMID- 18332936
TI  - Liver transplantation for the sequelae of intra-operative bile duct injury.
AB  - BACKGROUND: Intra-operative bile duct injuries (IBDI) are potentially severe
      complications of the treatment of benign conditions, with unpredictable long-term
      results. Multiple procedures are frequently needed to correct these
      complications. In spite of the application of these procedures, patients with
      severe injuries can develop irreversible liver disease. Liver transplantation
      (LT) is currently the only treatment available for such patients, but little
      information has been published concerning the results of LT. METHODS: Eight
      patients with LT for end-stage liver disease for IBDI were studied
      retrospectively. They had failure of multiple previous treatments and experienced
      recurrent episodes of cholangitis, oesophageal variceal bleeding, severe
      pruritus, refractory ascites and spontaneous peritonitis. RESULTS: Mean recipient
      hepatectomy time was of 243 minutes (range 140-295 min), the complete procedure
      averages 545 minutes (260-720) and intraoperative red-blood-cells consumption was
      6.5 units (1-7). One patient required reoperation due to perforation of a Roux-en
      Y loop, and three developed minor complications (2 wound infections, I inguinal
      lymphocele). One patient died due to nosocomial pneumonia (mortality rate 12.5%).
      One patient required retransplantation due to delayed hepatic artery thrombosis.
      At follow-up 75% of patients are alive with normal graft function and an
      excellent quality of life. CONCLUSIONS: LT represents a safe curative treatment
      for end-stage liver disease after IBDI, albeit a major undertaking in the context
      of a surgical complication in the treatment of benign disease. The complications
      of the surgical procedure and the long-standing immunosuppression impart a high
      cost for resolutions of these sequelae but LT represents the only long-term
      effective treatment for these selected patients.

PMID- 18332938
TI  - Dr Kenneth W Warren. 1911-2001.

PMID- 18332937
TI  - The early days of HPB: a personal reminiscence.

PMID- 18332939
TI  - Management of the left hepatic duct during extended right hepatectomy.

PMID- 18332940
TI  - Bronchobiliary fistula complicating oriental cholangiohepatitis.
AB  - Bronchio biliary fistula in adults is a rare event defined by the passage of bile
      into the bronchus and the sputum (biloptysis).Typically these lesions occur in
      the congenital form, as a result of thoracoabdominal trauma, or in rare instances
      as a result of iatrogenic injury or long-standing biliary tract disease and
      obstruction. In this paper, we report a novel case of a fatal bronchobiliary
      fistula that developed in a 67-year-old Chinese male with Oriental
      cholangiohepatitis. To our knowledge, this is the first case report of a
      bronchobiliary fistula complicating the clinical management of a patient with
      this disease.

PMID- 18332941
TI  - Hepatocellular carcinoma in a patient with focal nodular hyperplasia.
AB  - BACKGROUND: Focal nodular hyperplasia is an uncommon liver tumour that typically
      requires no therapeutic intervention. CASE OUTLINE: A 43-year-old woman with a 20
      year history of oral contraceptive use presented with symptomatic bilateral liver
      masses. Biopsy revealed hepatocellular carcinoma in the right hemiliver and focal
      nodular hyperplasia in the left hemiliver. At operation,t he patient was noted to
      have multiple liver nodules bilaterally, and all intraoperative biopsies were
      consistent with focal nodular hyperplasia including a biopsy taken from the
      region that demonstrated carcinoma preoperatively. Because of the earlier biopsy
      results and the patient's preoperative symptoms, a right hemihepatectomy was
      performed. Final pathology revealed hepatocellular carcinoma directly adjacent to
      an area of focal nodular hyperplasia, as well as multiple other areas of
      hyperplastic liver tumour. DISCUSSION: Although focal nodular hyperplasia is
      believed to be benign, few studies have followed patients with this tumour beyond
      three years. Longer-term follow-up studies are needed to determine the natural
      history of focal nodular hyperplasia, potentially focussing on a subset of
      patients with either diffuse tumours or prolonged oral contraceptive use.

PMID- 18332942
TI  - Malignant transformation of hepatic adenoma with recurrence after resection.

PMID- 18332943
TI  - A small leiomyosarcoma of the pancreas treated by local excision.
AB  - BACKGROUND: Leiomyosarcoma of the pancreas is a very rare tumour; only 33 cases
      have been reported in the English literature. Because these tumours tend to be
      large and locally advanced, extended resection such as pancreatoduodenectomy or
      distal pancreatectomy has been advocated. CASE OUTLINE: A 25-year-old woman with
      left-sided back pain had a small low-density lesion (2 x 2 cm) in the pancreatic
      body on computed tomography (CT). The tumour was initially diagnosed as a
      pseudocyst and was managed conservatively. A repeat CT scan 10 months later
      showed an increase in the size of the lesion (3.5 x 3.5 cm) with contrast
      enhancement of a high-density area. The diagnosis was therefore changed to
      papillary-cystic neoplasm. At laparotomy, the tumour seemed to be arising from
      the mid-body of the pancreas with no invasion into surrounding organs. Local
      excision of the tumour was performed. Pathological examination revealed a
      leiomyosarcoma of the pancreas. DISCUSSION: Complete surgical resection offers
      the only potential chance of cure for patients with leiomyosarcoma of the
      pancreas.The lack of evidence of recurrence at three-and-a-half years suggests
      that the less invasive surgical procedure in the present case has been curative.
      Careful and intraoperative exploration was important to determine the best
      surgical procedure.

PMID- 18332946
TI  - Laparoscopic cholecystectomy in the grossly obese: 4 years experience and review
      of literature.
AB  - BACKGROUND: Conventional abdominal surgery in grossly obese patients is
      associated with an increased rate of postoperative complications; thus,
      laparoscopic surgery may be preferred in these patients. PATIENTS AND METHODS: A
      prospective analysis was performed of 20 grossly obese patients who underwent
      laparoscopic cholecystectomy between April 1996 and April 2000 for symptomatic
      non-complicated gallstone disease. RESULTS: Technical problems at operation
      included difficulty with induction of pneumoperitoneum and introduction of the
      most lateral subcostal port, retraction of the gallbladder fundus, the need for
      longer instruments and the closure of the fascia. Laparoscopic cholecystectomy
      was successfully completed in 19 patients, but one patient required conversion to
      open operation. There were no anaesthetic difficulties. Two patients developed
      minor chest infections. The mean hospital stay was 2.9 days. CONCLUSION:
      Laparoscopic cholecystectomy is feasible and can be recommended for symptomatic
      gallstone disease in grossly obese patients.

PMID- 18332947
TI  - Percutaneous drainage of hydatid cyst of the liver: long-term results.
AB  - BACKGROUND: Previously surgical operation was the only accepted treatment for
      hydatid liver cysts. Recently percutaneous management has become more preferable
      because of its low morbidity rate and lower cost. PATIENTS AND METHODS: In all,
      101 patients harbouring 120 hydatid cysts of the liver were treated by
      percutaneous drainage between October 1994 and December 1997. Of these cysts, 89
      were in the right liver and 31 in the left liver.Thirty-one patients had had
      previous operations for hydatid disease. All cysts had an anechoic or hypoechoic
      unilocular appearance on ultrasound scan. The mean dimension of the cysts was
      7.5+/-2.9 cm (range 3-10.4 cm). All patients received oral albendazole 10 mg/kg
      perioperatively. After aspiration under sonographic guidance, cysts were
      irrigated with 95% ethanol. RESULTS: The amount of cyst fluid aspirated was 220+/
      75 ml and the amount of irrigation solution used was 175+/-42 ml. Four patients
      developed mild fever and three had urticaria. Mean length of hospital stay was
      2.1+/-0.7 (range 1-4) days, and patients were followed up for 43-62 months (mean
      54+/-5.4 months). Maximal cyst diameter decreased from 7.5+/-2.9 cm to 3.2+/-15
      cm (p<0.001). Sonographic examinations revealed high-level heterogeneous echoes
      in the cyst cavity (heterogeneous echo pattern), while the cyst cavity was
      completely obliterated by echogenic material (pseudotumour echo pattern).
      DISCUSSION: Most hydatid cysts of the liver can be managed successfully by a
      combination of drug therapy and percutaneous drainage.

PMID- 18332948
TI  - Spontaneous hepatic rupture: a report of five cases.
AB  - BACKGROUND: Spontaneous hepatic rupture is a well recognised but rare condition.
      Because of the difficulty in diagnosis, it is often associated with a high
      mortality rate. Pregnant women with HELLP syndrome are more prone to hepatic
      rupture, but it can also occur with other liver pathology. Different modalities
      of treatment, including liver resection, packing, hepatic artery ligation and
      even liver transplantation have been described for this condition. PATIENTS AND
      RESULTS: We report a series of five cases, three of which were associated with
      pregnancy and two with no identifiable pathology. Pre-operative diagnosis was not
      made in any of these cases.Two of the five patients had hepatic resection, two
      had peri-hepatic packing and one was treated with laparoscopic drainage.
      DISCUSSION: From our experience we conclude that no single form of treatment is
      applicable to all cases of hepatic rupture.The treatment should be
      individualised,depending on the extent of hepatic rupture and the expertise
      available, to obtain best outcome.

PMID- 18332949
TI  - II. The Endocrine and Pancreatic Unit at the University of Verona, Italy.

PMID- 18332950
TI  - Arrest of liver haemorrhage secondary to percutaneous liver biopsy of a
      haemangioma with fibrin glue.
AB  - BACKGROUND: Haemorrhage resulting from blunt and penetrating injury to the liver
      remains a difficult therapeutic problem, often resulting in massive
      intraperitoneal blood loss. Perihepatic liver packing and inflow occlusive
      techniques in combination with finger fracture exploration of injuries to allow
      vessel ligation are the mainstays if treatment with normal liver parenchyma. More
      recently fibrin glue haemostatic agents have been used to arrest traumatic
      haemorrhage from the liver. We report a case of the use of fibrin glue to arrest
      the bleeding caused by the percutaneous biopsy of a liver haemangioma. CASE
      OUTLINE: A 42 year-old woman underwent percutaneous diagnostic biopsy of a liver
      lesion and subsequently experienced shock secondary to massive bleeding from the
      biopsy site. At laparotomy there was massive bleeding from the puncture site of
      the liver lesion. Control of haemorrhage was obtained by injecting fibrin glue
      down the biopsy site tract. This manoeuvre resulted in complete arrest of
      haemorrhage with no adverse effect. DISCUSSION: The use of fibrin glue as a
      haemostatic agent in trauma is an important adjunct to perihepatic liver packing
      and finger fracture exploration of injuries. It may have exceptional utility in
      patients with penetrating trauma to the liver by direct intraparenchymal
      injection. This case illustrates that fibrin glue can be used to arrest bleeding
      from vascular tumours such as haemangiomas. It may help to minimise bleeding for
      all percutaneous liver biopsies.

PMID- 18332951
TI  - Regional pancreatectomy and transverse colectomy with mesenteric vascular
      reconstruction for inflammatory pseudotumour of the head of pancreas and
      mesenteric root.
AB  - BACKGROUND: Inflammatory myofibroblastic pseudotumour is a rare pancreatic
      lesion. CASE OUTLINE: A 32-year-old woman with such a tumour was treated by a
      radical operation comprising proximal pancreatic-duodenectomy (Whipple Procedure)
      and transverse colectomy with resection and reconstruction of the superior
      mesenteric artery and vein. She remains well 6 years later. DISCUSSION: The
      importance of aggressive surgical clearance rather than chemotherapy is
      highlighted in the management of patients with these unusual tumours.

PMID- 18332952
TI  - Post-traumatic pseudoaneurysm of the common hepatic artery with duodenal fistula.
AB  - BACKGROUND: Post-traumatic pseudoaneurysm of the hepatic artery is rare,
      especially after blunt abdominal trauma; an even more rare occurrence is enteric
      fistulisation. CASE OUTLINE: A 29-year-old man was admitted with an acute episode
      of upper gastrointestinal bleeding three months after blunt abdominal trauma and
      was found to have an hepatic artery pseudoaneurysm with duodenal fistula.
      Surgical treatment was by ligature of the artery and duodenal closure with
      omental patch. DISCUSSION: There is one previous case report of hepatic artery
      pseudoaneurysm as a delayed complication of blunt abdominal trauma. The presence
      of a haematoma in the hepatoduodenal ligament after blunt trauma should raise the
      suspicion of hepatic artery injury, and surgical exploration may prevent the
      subsequent development of pseudoaneurysm. CT scan has become an important
      instrument both in diagnosis and in surgical planning.

PMID- 18332953
TI  - Adenomyoma of the common hepatic duct.
AB  - BACKGROUND: Adenomyoma occurs most commonly in the fundus of the gallbladder,
      seldom in other parts of the gallbladder and rarely in the extrahepatic biliary
      tree, where most lesions are localised to the common bile duct or papilla of
      Vater. Adenomyoma of the common hepatic duct is extremely rare. To the best of
      our knowledge, only three cases have been reported so far. CASE OUTLINE: A 51
      year-old woman was admitted with a three month history of attacks of right upper
      abdominal pain, nausea, vomiting and fever. Laboratory data, ultrasonography,
      ERCP and CT confirmed slight cholestasis and proximal bile duct dilatation due to
      a tumour within the common hepatic duct. Cholecystectomy was performed with
      excision of the suprapancreatic common bile duct including the convergence of the
      hepatic ducts plus lymphadenectomy and Roux-en-Y hepaticojejunostomy. Frozen
      section histology showed the benign nature of the lesion and a tumour-free
      resection line. Final histology showed adenomyoma. The patient has remained
      symptom free for more than 30 months. DISCUSSION: Although adenomyoma is a benign
      lesion and the surgical strategy has not been established, complete excision with
      frozen section is recommended to exclude small malignant foci and local
      recurrence as well as to avoid surgical over-treatment.

PMID- 18332954
TI  - Two cases of ectopic liver attached to the gallbladder wall.
AB  - BACKGROUND: Ectopic liver tissue is occasionally found either attached to the
      gallbladder or elsewhere in the upper abdomen. CASE OUTLINES: A 49-year-old man
      and a 39-year-old woman were found to have a tongue of liver tissue attached to
      the serosa of the gallbladder (but separate from the liver) during laparoscopic
      cholecystectomy for gallstones. The ectopic liver was removed with the
      gallbladder and was histologically normal in each case. DISCUSSION: Several
      embryological hypotheses have been advanced to explain the development of ectopic
      liver. The anomaly is usually discovered incidentally at operation. Although the
      tissue is histologically normal.it can develop the same conditions as orthotopic
      liver.

PMID- 18332955
TI  - Abdominal aortic aneurysm and hepatocellular carcinoma: a one-stage approach.
AB  - BACKGROUND: The operative management of abdominal aortic aneurysm (AAA) and co
      existing intra-abdominal malignancy has been a long-standing controversy. It is
      unclear whether a single-stage or a two-stage approach is the more appropriate
      therapeutic option and also which lesion should be treated first. CASE OUTLINE:
      An 82-year-old man with a 4 x 5-cm mass in the left liver (segment IV), suspected
      to be a hepatocellular carcinoma (HCC), had a concomitant 6-cm infrarenal AAA. At
      the same operation he underwent a left hepatectomy followed by repair of the
      aneurysm. He was discharged on the 17th postoperative day. To the best of our
      knowledge, this is the third report in the world literature of a patient who
      underwent a successful simultaneous resection of an AAA and HCC and the first in
      which the liver resection was performed first. DISCUSSION: We recommend liver
      resection and AAA repair in a single-stage procedure, regardless of the time
      sequence of the procedures. This approach can be considered safe, and the
      theoretical risk of graft infection can be kept to a minimum.

PMID- 18332956
TI  - Integrated blood conservation programme to minimise blood loss and transfusion
      requirements in hepatic resection.

PMID- 18332958
TI  - Pancreatic tuberculosis: an elusive diagnosis.
AB  - BACKGROUND: Pancreatic tuberculosis is a rare disease. Its presenting features
      are usually vague and non-specific, while the radiological features mimic
      pancreatic malignancy in many cases and pancreatitis in others. Ultrasound- or CT
      guided fine-needle aspiration cytology (FNAC) or biopsy may show caseating
      granulomatous inflammation but microbiological confirmation may not always be
      possible. Laparotomy may be required if other investigations prove inconclusive.
      The response to treatment is good. CASE OUTLINES: We report two young men with
      pancreatic tuberculosis. The diagnosis was obtained by FNAC in one and laparotomy
      in the other. Each patient responded to anti-tuberculous chemotherapy and is now
      asymptomatic. CONCLUSION: Tuberculosis should be considered in the differential
      diagnosis of an obscure pancreatic mass, and the condition is readily curable.

PMID- 18332959
TI  - Expandable metal stents in chronic pancreatitis.
AB  - BACKGROUND: Biliary obstruction in chronic pancreatitis may be relieved by the
      insertion of a biliary endoprosthesis. Stenting is usually achieved with a
      plastic device, but self-expandable metal stents may also be used. CASE OUTLINES:
      Two patients are described with severe chronic pancreatitis complicated by
      biliary obstruction and portal vein thrombosis, who underwent insertion of
      metallic biliary endoprostheses. In both patients the endoprostheses became
      occluded, at 12 and 7 months respectively, which necessitated open operation.
      Both patients experienced surgical complications and one patient died
      postoperatively. DISCUSSION: The use of metal endoprostheses in chronic
      pancreatitis may result in occlusion, necessitating open operation. Such stents
      should be used with caution in these patients, who are likely to be high-risk
      surgical candidates.

PMID- 18332960
TI  - Focus on the gut in acute pancreatitis.

PMID- 18332962
TI  - Hepatectomy for pyogenic liver abscess.
AB  - BACKGROUND: Commensurate with the advances in diagnostic and therapeutic
      radiology in the past two decades, percutaneous needle aspiration and catheter
      drainage have replaced open operation as the first choice of treatment for both
      single and multiple pyogenic liver abscesses. There has been little written on
      the place of surgical resection in the treatment of pyogenic liver abscess due to
      underlying hepatobiliary pathology or after failure of non-operative management.
      METHODS: The medical records of patients who underwent resection for pyogenic
      liver abscess over a 15-year period were retrospectively reviewed. The
      demographics, time from onset of symptoms to medical treatment and operation,
      site of abscess, organisms cultured, aetiology, reason for operation, type of
      resection and outcome were analysed. There were 49 patients in whom the abscesses
      were either single (19), single but multiloculated (11) or multiple (19). The
      median time from onset of symptoms to medical treatment was 21 days and from
      treatment to operation was 12 days. The indications for operation were underlying
      hepatobiliary pathology in 20% and failed non-operative treatment in 76%. Two
      patients presented with peritonitis from a ruptured abscess. RESULTS: The
      resections performed were anatomic (44) and non-anatomic (5). No patient suffered
      a recurrent abscess or required surgical or radiological intervention for any
      abdominal collection. Antibiotics were ceased within 5 days of operation in all
      but one patient. The median postoperative stay was 10 days. There were two deaths
      (4%), both following rupture of the abscess. DISCUSSION: Except for an initial
      presentation with intraperitoneal rupture and, possibly, cases of hepatobiliary
      pathology causing multiple abscesses above an obstructed duct system that cannot
      be negotiated non-operatively, primary surgical treatment of pyogenic liver
      abscess is not indicated. Non-operative management with antibiotics and
      percutaneous aspiration/drainage will be successful in most patients. If non
      operative treatment fails, different physical characteristics of the abscesses
      are likely to be present and partial hepatectomy of the involved portion of liver
      is good treatment when performed by an experienced surgeon.

PMID- 18332961
TI  - The role of the intestine in the pathophysiology and management of severe acute
      pancreatitis.
AB  - BACKGROUND: The outcome of severe acute pancreatitis has scarcely improved in 10
      years. Further impact will require new paradigms in pathophysiology and
      treatment. There is accumulating evidence to support the concept that the
      intestine has a key role in the pathophysiology of severe acute pancreatitis
      which goes beyond the notion of secondary pancreatic infection. Intestinal
      ischaemia and reperfusion and barrier failure are implicated in the development
      of multiple organ failure. DISCUSSION: Conventional management of severe acute
      pancreatitis has tended to ignore the intestine. More recent attempts to rectify
      this problem have included 1) resuscitation aimed at restoring intestinal blood
      flow through the use of appropriate fluids and splanchnic-sparing
      vasoconstrictors or inotropes; 2) enteral nutrition to help maintain the
      integrity of the intestinal barrier; 3) selective gut decontamination and
      prophylactic antibiotics to reduce bacterial translocation and secondary
      infection. Novel therapies are being developed to limit intestinal injury, and
      these include antioxidants and anti-cytokine agents. This paper focuses on the
      role of the intestine in the pathogenesis of severe acute pancreatitis and
      reviews the implications for management.

PMID- 18332963
TI  - Non-operative management of pyogenic liver abscess.
AB  - BACKGROUND: Liver abscess is a serious disease traditionally managed by open
      drainage. The advances in interventional radiology over the last two decades have
      allowed a change in approach to this condition. We have reviewed our experience
      in managing liver abscess over the last 7 years. METHODS: Details of all patients
      admitted with liver abscess between 1995 and 2002 were prospectively entered onto
      our database. A review was performed to document the use of imaging and drainage
      techniques. Aetiology, morbidity, mortality and duration of hospital stay were
      recorded. RESULTS: Forty-two patients (median age 53 [22-85] years; M:F 18:24)
      were admitted with liver abscess (multiple abscess 20); 19 cases were of portal
      tract origin, 16 cases were of biliary tract origin and 7 cases were spontaneous.
      Forty-one patients were managed non-operatively, all received antibiotics
      (cephalosporins 76%, metronidazole 88%, quinolones 33%). Diagnosis was made on
      ultrasound scan (22) or CT (20). Five patients were managed with antibiotics
      alone. Fifteen patients were managed initially with percutaneous aspiration and
      five subsequently required percutaneous drainage. Twenty-one patients had primary
      percutaneous drainage, nine requiring a further procedure (aspiration 3, drainage
      6). One patient underwent hepatic resection. Median hospital stay was 16 (6-35)
      days. There was one death, but no procedure-related morbidity. DISCUSSION: Non
      operative management of solitary and multiple liver abscesses is safe and
      effective.

PMID- 18332964
TI  - Gallstone pancreatitis: does discharge and readmission for cholecystectomy affect
      outcome?
AB  - BACKGROUND: Conventional surgical wisdom is that a patient with gallstone
      pancreatitis should have the gallbladder removed during their initial
      hospitalization. However, patients are now often discharged to await operating
      room availability. METHODS: A retrospective review of all cases of gallstone
      pancreatitis at the Foothills Hospital between 1992 and 1996 was undertaken.
      Patients with a first attack of mild gallstone pancreatitis were studied.
      RESULTS: In all, 164 patients were identified: 90 patients were discharged for
      readmission cholecystectomy (discharged group), and 74 patients had the
      cholecystectomy before discharge (in-hospital group). Over the 5-year time period
      the proportion of patients discharged for readmission cholecystectomy increased
      from 27% to 67% (p<0.01). The total number of days waited for operation was
      greater in the discharged group versus in-hospital group: 40+/-69 days versus 8+/
      10 days respectively (mean+/-SD). There was a trend towards an increased total
      number of days in hospital in the in-hospital group, 15.5+/-17 days versus 10.7+/
      16 days. In the discharged group 20% (18 of 90) of patients experienced an
      adverse event requiring readmission while awaiting operation. Three had
      documented recurrent pancreatitis, 10 experienced recurrent pain, and 5 developed
      acute cholecystitis. There were no deaths in either group. DISCUSSION: Twenty
      percent of patients with gallstone pancreatitis who are discharged to await
      operating room time (average wait 40 days) will require readmission for biliary
      symptoms.

PMID- 18332965
TI  - Value of laparoscopy and laparoscopic ultrasonography in determining
      resectability of colorectal hepatic metastases.
AB  - BACKGROUND: The aim was to assess the value of laparoscopy and laparoscopic
      ultrasonography (LUS) in selecting patients for resection of colorectal hepatic
      metastases. METHODS: Sixty patients with potentially resectable colorectal
      hepatic metastases after helical computer tomography (CT) and scheduled to
      undergo laparoscopy and LUS were studied retrospectively. Primary outcome
      measurement was the number of cases in which laparoscopy and LUS resulted in a
      change of therapeutic approach. RESULTS: Of the 60 patients, 59 patients were
      examined by LUS and/or laparoscopy. The small intestine was perforated due to
      adhesions in two patients, necessitating open exploration in one of them. In 17
      patients (29%) the combined laparoscopic procedure yielded results prohibiting
      resection; another 6 patients were denied resection on other grounds. Of the 36
      patients who underwent open exploration, 31 underwent resection. Combined
      laparoscopy and LUS predicted resectability correctly in 86% of the patient
      group. Compared with resection, the sensitivity of both CT and LUS to detect
      lesions was 91%. DISCUSSION: Laparoscopy and LUS can avoid open exploration
      without resection in a substantial number of patients considered eligible for
      resection of colorectal hepatic metastases based on CT. LUS does not seem to
      detect more metastases than CT.

PMID- 18332966
TI  - Choledochal cysts in adults and their complications.
AB  - BACKGROUND: Despite refinements in the management of choledochal cysts in
      children, an increasing number of patients present with ongoing symptoms in adult
      life. The aim of this study was to review the management of adult patients with
      choledochal cysts in a tertiary referral centre. METHOD: A retrospective review
      was carried out of all adult patients presenting with choledochal cysts to this
      department between 1992 and 2000. Patient records were reviewed and detailed
      analyses were made of the clinical presentation, radiological and biochemical
      findings, anatomical anomalies, management, complications and outcomes. RESULTS:
      Of 16 patients (12 women and 4 men; median age 23 years), 8 had undergone
      previous upper gastrointestinal operations before referral, including 5 who had
      had previous cyst drainage procedures. All patients underwent elective complete
      cyst excision with Roux-en-Y hepaticojejunostomy. There were no operative deaths
      and there was a low early postoperative morbidity rate (25%). There was no
      evidence of biliary malignancy in any cyst. During a median postoperative follow
      up of 44 months, five patients (31%) continued to experience cholangitis and two
      of these required additional revisional procedures, but are now symptom-free.
      CONCLUSION: Patients with choledochal cysts should be referred to specialised
      tertiary surgical units. Total choledochal cyst excision with Roux-en-Y
      hepaticojejunostomy is the treatment of choice. Patients with previous inadequate
      cyst excisional procedures should undergo revisional surgery, to reduce recurrent
      symptoms and the risk of developing cholangiocarcinoma.

PMID- 18332967
TI  - Pancreatic acinar cell carcinoma presenting as acute pancreatitis.
AB  - BACKGROUND: Acinar cell carcinoma (ACC) is a rare pancreatic neoplasm, and its
      presentation with acute pancreatitis has not been reported previously. CASE
      OUTLINE: A 70-year-old man presented with acute pancreatitis, and a spiral CT
      scan showed a 5-cm tumour in the body of the pancreas. Distal pancreatectomy was
      performed, and histological examination showed an ACC. DISCUSSION: This is a
      newly reported mode of presentation for a rare pancreatic tumour.

PMID- 18332968
TI  - Three cases of massive bleeding from pancreatic pseudocysts.
AB  - BACKGROUND: Intracystic bleeding is an infrequent but potentially lethal
      complication of pancreatic pseudocyst. Early preoperative diagnosis is an
      important aspect of effective management. CASE OUTLINES: Three patients presented
      with bleeding into a pancreatic pseudocyst. One was managed by intracystic
      ligation and external drainage, one was managed with postoperative angiographic
      embolisation and the third patient underwent angiographic embolisation as
      definitive treatment. DISCUSSION: Massive bleeding from a pseudoaneurysm
      associated with pseudocyst of the pancreas carries a high mortality and morbidity
      rate. A high index of suspicion for patients with suggestive clinical signs and
      symptoms plus careful evaluation on a thin-sliced contrast-enhanced CT scan with
      early and delayed films corroborated by selective angiography leads to better
      management.

PMID- 18332969
TI  - Digestive complications of gallstones lost during laparoscopic cholecystectomy.
AB  - INTRODUCTION: Serious complications can ensue if a gallstone is dropped into the
      peritoneal cavity during laparoscopic cholecystectomy and not retrieved. CASE
      OUTLINE: A 75-year-old-man was admitted with intestinal obstruction 8 years after
      laparoscopic cholecystectomy. Ultrasound scan and a contrast x-ray of the small
      bowel showed a gallstone within the small bowel lumen that CT scan had failed to
      identify. Laparotomy showed a Meckel's diverticulum plus a 4 x 6-cm gallstone in
      the terminal ileum. The gallstone had penetrated into the Meckel's diverticulum
      before migrating into the ileum and obstructing it. DISCUSSION: Gallstones lost
      during laparoscopic cholecystectomy can cause an intraperitoneal abscess. In
      addition, they can migrate through the anterior or posterior abdominal wall or
      the diaphragm and into the urinary tract or bronchus. The resulting abscess can
      obstruct the digestive tract or drain into the digestive tract to cause a
      communicating abscess. It can also drain through the abdominal wall and the
      digestive tract to cause an enterocutaneous fistula. Lastly, the stone can
      migrate into the intestine and cause gallstone ileus. Following laparoscopic
      cholecystectomy, patients with a lost gallstone may suffer from abdominal pain
      and fever within days or months. Thus, all dropped gallstones should be removed
      during laparoscopy.

PMID- 18332970
TI  - Massive hemorrhage and infarction complicating focal nodular hyperplasia of the
      liver.
AB  - BACKGROUND: Spontaneous infarction or hemorrhage of focal nodular hyperplasia
      (FNH) has rarely been reported in the literature. CASE OUTLINE: A 43-year-old
      woman presented with upper abdominal pain and anemia. CT scan showed an enormous
      perihepatic hematoma. Trisegmentectomy successfully dealt with the problem.
      CONCLUSION: Although conservative management of FNH is often adopted, this case
      illustrates that these lesions can undergo massive bleeding.

PMID- 18332971
TI  - Pancreatoduodenectomy for unusual tumours.

PMID- 18332972
TI  - Difficult laparoscopic cholecystectomy in acute cholecystitis: use of 'finger
      port', a new approach.
AB  - BACKGROUND: Adhesions in acute cholecystitis tax even the more experienced
      operator during laparoscopic cholecystectomy. Blunt and sharp dissection,
      electrocautery, laser, hydrodissection, and ultrasonic dissection may all have
      their limitations. Thus there is a need for an alternative and more effective
      method. METHOD: Laparoscopic cholecystectomy was carried out in 281 patients with
      acute cholecystitis. Separation of the gallbladder from the adherent structures
      was carried out in 13 patients, using the forefinger of the left hand introduced
      through the right hypochondrial port. In two patients a second finger was
      introduced through the epigastric port. RESULTS: The mean time required for the
      dissection was 7.9 minutes. Finger dissection failed in three patients because of
      dense adhesions on a high subcostal position of the gallbladder. DISCUSSION:
      Finger dissection is easy, fast, and limits injury because of the direct vision
      and tactile sensation, which are missing in other methods of laparoscopic
      dissection.

PMID- 18332973
TI  - Resection of renal metastases to the pancreas: a surgical challenge.
AB  - BACKGROUND: Metastasis to the pancreas from renal cell carcinoma (RCC) is
      distinctly uncommon. Most cases are detected at an advanced stage of the disease
      and are thus unsuitable for resection. A solitary RCC metastasis to the head of
      pancreas is rarely encountered and, although it is potentially amenable to
      surgical resection, surgeons may be hesitant to perform pancreatoduodenectomy.
      CASES OUTLINES: Two patients with a solitary RCC metastasis to the head of
      pancreas were treated by pancreatoduodenectomy, while a third with multiple RCC
      metastases declined any treatment. Two of the patients were asymptomatic, and one
      presented with anaemia and mild abdominal pain. Computed tomography (CT) and
      angiography were used to exclude other metastases and to assess resectability of
      the pancreatic tumour. All three patients are still alive, those with resectable
      disease at 2 years and 9 years and the one with irresectable disease at 4 years.
      DISCUSSION: Isolated RCC metastasis to the pancreas is a rare event. Patients
      present either on follow-up imaging or with symptoms such as mild abdominal pain,
      weight loss, jaundice, anaemia or gastrointestinal bleeding (whether occult or
      overt). Dynamic spiral CT can visualise the tumour and exclude distant
      metastasis. Angiography often reveals a highly vascularised tumour and will help
      to assess resectability. In the absence of widespread disease, pancreatic
      resection can provide long-term survival in metastatic RCC, although few cases
      have been reported with lengthy follow-up. The prognosis is better than for
      pancreatic adenocarcinoma.

PMID- 18332974
TI  - The sphincter of Oddi and acute pancreatitis--revisited.
AB  - BACKGROUND: One of the rare causes of recurrent acute pancreatitis is sphincter
      of Oddi dysfunction. This condition is objectively diagnosed by manometry of the
      sphincter of Oddi. An abnormally elevated sphincter of Oddi basal pressure has
      been shown to predict patients who have a successful outcome after transduodenal
      sphincteroplasty and pancreatic duct septoplasty. METHODS: Forty-nine patients
      presenting with recurrent pancreatitis and who had manometric stenosis of the
      sphincter of Oddi were treated by transduodenal division of the sphincter of
      Oddi. Clinical follow-up was conducted over a minimum of 2 years. RESULTS: In
      all, 43 patients were either cured or improved. None of these patients had any
      further episodes of pancreatitis. Three of these patients developed recurrent
      symptoms and were noted to have restenosis of the sphincter of Oddi. They were
      treated by insertion of an endoscopic stent into the pancreatic duct. CONCLUSION:
      The results from this series of patients re-affirm the efficacy of transduodenal
      sphincteroplasty and septoplasty for treatment of sphincter of Oddi stenosis in
      patients presenting with recurrent acute pancreatitis.

PMID- 18332975
TI  - Liver regeneration in living-related donors after harvesting of liver segments II
      and III or II, III and IV.
AB  - BACKGROUND: CT-assisted volumetry permits an estimation of the volume of the
      graft in liver transplantation, as well as monitoring the donor's liver
      regeneration. The aim of the study was to observe the restitution of liver tissue
      in donors after harvesting of the liver fragment for living-related liver
      transplantation (LRLT). METHODS: The size of the whole liver and of segments II,
      III and IV was assessed by preoperative CT volumetry in 29 living-related liver
      donors. Segments II and III were harvested in 22 patients, segments II, III and
      IV in 6 patients. The remnant liver was assessed by CT volumetry on the 7th and
      30th postoperative days. RESULTS: The correlation between the calculated volume
      of the graft and its weight was linear (r=0.56, p<0.04). Postoperative CT
      volumetry of the liver of living-related donors showed a different pattern of
      volume restoration (regeneration index) at both 7 and 30 days between donors who
      sacrificed segments II and III and those who sacrificed segments II, III and IV.
      The mean regeneration indexes were significantly higher in donors of segments II,
      III and IV as compared with donors of segments II and III (7 days, p<0.02; 30
      days, p<0.05). DISCUSSION: It is possible that the donor's liver displays a
      different pattern of growth due to the alteration in blood supply to segment IV.

PMID- 18332976
TI  - Laparoscopic cholecystectomy: incidents and complications. A retrospective
      analysis of 9542 consecutive laparoscopic operations.
AB  - BACKGROUND: Even though laparoscopic cholecystectomy (LC) has become the
      customary method for treating gallstones, some incidents and complications appear
      rather more frequently than with the open technique. Several aspects of these
      complications and their treatment possibilities are analysed. MATERIALS AND
      METHODS: Over the last 9 years 9542 LCs have been performed at this centre, of
      which 13.9% were carried out for acute cholecystitis, 38.4% in obese patients and
      7.6% in patients aged >65 years. RESULTS: The main operative incidents
      encountered were haemorrhage (224 cases, 2.3%), iatrogenic perforation of the
      gallbladder (1517 cases, 15.9%) and common bile duct (CBD) injuries (17 cases,
      0.1%). Conversion to open operation was necessary in 184 patients (1.9%), usually
      due to obscure anatomy as a result of acute inflammation. The main postoperative
      complications were bile leakage (54 cases), haemorrhage (15 cases), sub-hepatic
      abscess (10 cases) and retained bile duct stones (11 cases). Ten deaths were
      recorded (0.1%). DISCUSSION: Most of the postoperative incidents (except bile
      duct injuries) were solved by laparoscopic means. Among patients with
      postoperative complications 28.9% required revisional surgery. In 42.2% of cases
      minimally invasive procedures were used successfully: 15 laparoscopic re
      operations (for choleperitoneum, haemoperitoneum and subhepatic abscess) and 22
      endoscopic sphincterotomies (for bile leakage from the subhepatic drain and for
      retained CBD stones soon after operation). The good results obtained allow us to
      recommend these minimally invasive procedures in appropriate patients.

PMID- 18332977
TI  - A 10-year experience in the management of gallbladder cancer.
AB  - BACKGROUND: The aim of this retrospective study was to review all patients
      diagnosed with gallbladder cancer over a 10-year period to assess variables
      affecting survival. METHODS: Patients diagnosed with gallbladder cancer from
      January 1990 to December 1999 were identified from the Lothian Surgical Audit
      database and a case-note review was performed. RESULTS: The 44 patients who were
      studied (33 women, 11 men) had a mean age of 66 years (range 42-90 years). The
      diagnosis was established preoperatively in 25 patients (57%), intraoperatively
      in 5 patients (11%) and incidentally following pathological examination of
      cholecystectomy specimens in 14 patients (32%). None of the 25 patients diagnosed
      preoperatively underwent curative operations (median survival 4 months). All five
      patients diagnosed at the time of attempted cholecystectomy had advanced
      irresectable disease (median survival 1 month). The overall median survival in 14
      patients with an incidental diagnosis of gallbladder cancer was 16 months;
      however, in eight of these patients who were considered to have had a potentially
      curative resection, the median survival was 38 months. DISCUSSION: The prognosis
      for patients diagnosed preoperatively or at the time of cholecystectomy is very
      poor. Patients with an incidental finding of gallbladder cancer have a
      significantly better prognosis and should be considered for further radical re
      resection.

PMID- 18332978
TI  - Parenchymal transection with ultrasonic scalpel in liver resection.
AB  - BACKGROUND: There is no ideal tool for parenchymal transection in liver resection
      and bleeding is still a major complication. The purpose of this study was to
      evaluate the usefulness of an ultrasonic scalpel and to describe our clinical
      experience in open liver resection. METHODS: An ultrasonic scalpel was used in
      seven consecutive patients undergoing liver resection. During parenchymal
      transection coagulation shears were used with the power level set at 2 or 3, and
      the blunt blades were selected. RESULTS: In each case, bleeding from the liver
      parenchyma was trivial, but haemostasis of large vessels required suture
      ligation. Postoperatively none of the patients experienced local technical
      complications such as haematoma, bile leak or infection. DISCUSSION: Although
      complete haemostasis of large vessels cannot be achieved, the ultrasonic scalpel
      may be used for parenchymal transection in liver resection to reduce blood loss.
      Larger series of patients are needed before a definitive statement regarding the
      efficacy of this method can be made.

PMID- 18332979
TI  - Extra-pancreatic end-to-side hepaticojejunostomy: a practical modification of the
      duodenum-preserving pancreatic head resection (DPPHR) for chronic pancreatitis.
AB  - BACKGROUND: Duodenum-preserving pancreatic head resection (DPPHR) is recognised
      for the surgical treatment of chronic pancreatitis. Approximately 15-20% of
      patients undergoing DPPHR require a synchronous biliary drainage procedure for
      stricture. METHODS AND RESULTS: This report describes a technical modification
      involving the placement of an extra-pancreatic end-to-side Roux
      hepaticojejunostomy utilising the same jejunal loop employed for
      pancreaticojejunal anastomosis. DISCUSSION: Extra-pancreatic end-side
      hepaticojejunostomy is a simple technical modification of DPPHR. The biliary
      anastomosis is constructed according to the well-established principles of
      biliary reconstruction and represents a safe and valuable technical option.

PMID- 18332980
TI  - Pancreatic resection for metastatic melanoma.
AB  - BACKGROUND: The pancreas is an occasional site of metastases from melanoma. It
      may be the only location of metastatic disease, but more often the melanoma
      metastasis to other organs as well. Treatment options are somewhat limited, and
      the role of operative treatment is poorly defined. CASE OUTLINES: Two patients
      presenting with abdominal pain were found to have pancreatic lesions. A 45-year
      old woman had a pylorus-preserving pancreatoduodenectomy for a mass in the head
      of pancreas; concurrent liver nodules were treated by segmental liver resection.
      A 55-year-old man had a total pancreatectomy for multiple pancreatic tumours.
      Both patients gave a history of ocular melanoma, diagnosed >10 years previously.
      They had no evidence of malignancy elsewhere. Histology of resected specimens
      confirmed metastatic melanoma with features consistent with an ocular primary.
      All resection margins were clear of malignancy, and no lymph node metastases were
      detected. At 6 months follow-up there were no signs of tumour recurrence.
      DISCUSSION: Complete surgical resection offers potential cure in selected
      patients with metastatic melanoma involving the pancreas, when there is no
      evidence of widespread disease.

PMID- 18332981
TI  - Implantation of migrated biliary stents in the digestive tract.
AB  - BACKGROUND: Biliary stents constitute an alternative for the palliative treatment
      of benign or malignant biliary obstruction, biliary strictures,
      choledocholithiasis, biliary fistulas from lateral lesions of the biliary duct or
      cystic duct leaks due to slippage of clip closure. Obstruction resulting in
      cholangitis is common. Proximal migration to the biliary duct or distal migration
      to the duodenum with subsequent passage per rectum are relatively frequent, but
      impaction and perforation of the bowel are rare. CASE OUTLINES: Two cases are
      reported. In one patient a migrated stent impacted in the caecal wall, and in the
      other the impaction produced a perforation of an adherent small bowel loop. Both
      patients were treated surgically and made an uneventful recovery. DISCUSSION:
      Biliary stents migrate in 8-10% of patients and are generally eliminated by
      natural means. Occasionally they impact and perforate the digestive tract,
      usually in the duodenum or other fixed areas or in bowel affected by adhesions
      due to a previous operation. Although endoscopy is the treatment of choice to
      retrieve them, operation should be performed whenever there is suspicion of
      perforation of the intestinal wall.

PMID- 18332982
TI  - Development of colonic stenosis following severe acute pancreatitis.
AB  - BACKGROUND: Colonic necrosis after acute pancreatitis is rare. When it does
      occur, it is commonly due to ischaemia or inflammation and may necessitate early
      colonic resection. CASE OUTLINE: A 72-year-old man developed colonic necrosis 6
      weeks after severe acute pancreatitis. CT scan revealed a bulky mass near the
      left colon. Barium enema and colonoscopy revealed stenosis of the left colonic
      flexure, and this segment of bowel was successfully resected. DISCUSSION: Severe
      acute pancreatitis must be recognised as a cause of colonic ischaemia and
      necrosis. The possible pathogenic mechanisms include severe local inflammation
      and an ischaemic process. This complication is associated with a very poor
      prognosis despite surgical intervention, but a timely resection may prevent
      further problems.

PMID- 18332983
TI  - Duodenal webs--no age limit.
AB  - BACKGROUND: Duodenal webs usually give rise to symptoms of gastric outlet
      obstruction in infancy, but they occasionally present in adulthood. CASE OUTLINE:
      We report an 82-year-old woman with an unusual cause of gastric outlet
      obstruction. Peptic ulcer stricture or carcinoma were suspected, but a CT scan
      and upper gastrointestinal endoscopy revealed that her symptoms were the result
      of duodenal webs. The webs were successfully dilated at endoscopy. DISCUSSION:
      Duodenal webs may rarely account for gastric outlet obstruction in adults.
      Failure to visualise the second and third parts of the duodenum at endoscopy
      means that the diagnosis may be missed. Diclofenac and slow-release potassium
      tablets may have played an aetiological role in the formation of the webs in this
      patient.

PMID- 18332984
TI  - Reconstruction of the main portal vein for a large saccular aneurysm.
AB  - BACKGROUND: A large aneurysm of the main portal vein is rare, and the appropriate
      surgical procedure is uncertain. Reconstruction of a main portal vein affected by
      a large saccular aneurysm is described. CASE OUTLINE: Abdominal pain led to the
      diagnosis of a large saccular aneurysm of the main portal vein in a 58-year-old
      woman who had undergone cholecystectomy 10 years earlier. At laparotomy a
      dorsolateral approach to the hepatoduodenal ligament was performed with no
      attempt at extensive separate exposure of the anatomical structures in the
      hepatoduodenal ligament, so as to avoid the devascularisation of the common
      hepatic duct and additional weakening of the portal vein wall. The aneurysm was
      longitudinally incised, and the portal vein was reconstructed from the walls of
      the aneurysm with a longitudinal running suture. The rest of the aneurysmal wall
      was wrapped around the portal vein, leaving it normal in size and contour.
      Recovery was uneventful. Follow-up CT scan showed a patent portal vein in the
      region of the former aneurysm. DISCUSSION: Large saccular aneurysms can rupture,
      bleed and cause death. The potential hazards of manipulation of large portal vein
      aneurysms are negligible in comparison with the possible complications of the
      aneurysm itself. In our opinion the ease with which the main portal vein was
      dissected and reconstructed make an elective operation in such cases a reasonable
      approach.

PMID- 18332985
TI  - Fibrolamellar hepatocellular carcinoma in pregnancy.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) is rare in pregnancy but can enlarge
      rapidly under these circumstances. CASE OUTLINE: A 25-year-old woman was
      diagnosed with HCC of fibrolamellar type immediately post-partum. One year after
      liver resection the patient remains well. DISCUSSION: This is only the second
      report of fibrolamellar carcinoma occurring in pregnancy. Other types of
      hepatocellular carcinoma in pregnancy have generally demonstrated a poor outcome,
      probably secondary to hormonal changes and increased liver vascularity.

PMID- 18332986
TI  - Omental and extraperitoneal abscesses complicating cholecystocolic fistula.
AB  - BACKGROUND: Acute cholecystitis resolves with conservative treatment in most
      patients, but empyema or perforation of an ischaemic area may develop, resulting
      in a pericholecystic abscess, bile peritonitis or a cholecysto-enteric fistula.
      CASE OUTLINE: A 63-year-old man presented with extraperitoneal and omental
      abscess formation complicating a cholecystocolic fistula secondary to gallbladder
      disease. Histological examination of the gallbladder and omentum showed
      xanthogranulomatous inflammation. CONCLUSION: A detailed literature review failed
      to demonstrate a previous report of this combination of rare complications of
      gallbladder disease.

PMID- 18332988
TI  - Liver transplantation is not indicated for cholangiocarcinoma.

PMID- 18332989
TI  - Future perspectives for hepatocellular carcinoma.
AB  - BACKGROUND: Five facets of hepatocellular carcinoma (HCC) are identified that
      impact on future directions in the management of the disease: epidemiology,
      prevention, screening, diagnosis and therapy. Recent papers on HCC have been
      reviewed, and predictions have been made on developments in HCC over the next
      decade. DISCUSSION: It is predicted that hepatitis B-related HCC will decrease
      with vaccination, while hepatitis C-related HCC will become an increasing
      problem. Antiviral treatment and chemopreventive agents will prevent HCC
      development. Whole-population screening will not be an option, but screening is
      justified for individuals who can pay for it. There will be more emphasis on the
      use of tumour markers. Transabdominal ultrasound and triphasic spiral computed
      tomography will remain important radiological imaging techniques. The results of
      liver resection will not improve unless neoadjuvant/adjuvant therapy is proven to
      be effective. More patients with initially unresectable HCC will be down-staged
      to become resectable with improvements in local, regional and systemic therapies.
      Liver transplantation will be increasingly used. Local ablative therapy will
      improve the quality of survival but will have no impact on overall survival
      compared with surgical resection. The author hopes to review the accuracy of
      these predictions in 2013.

PMID- 18332990
TI  - Detection of oncogenes in chronic pancreatitis.
AB  - BACKGROUND: The pathogenesis of chronic pancreatitis (CP) remains poorly
      understood. Recently, molecular biology has identified the genetic background for
      many patients with hereditary CP. In addition, a number of studies have focused
      on the detection of proto-oncogenes and tumour suppressor gene mutations in the
      pathogenesis of CP. So far, the use of these mutations (with the exception of
      mutations causing hereditary CP), as diagnostic and prognostic markers is still
      controversial. DISCUSSION: It is well known that the risk of pancreatic cancer in
      patients with CP, especially the hereditary form, is high. At present, there is
      insufficient evidence to show a clear relationship between the development of
      pancreatic cancer and certain mutations. New biotechnological methods, such as
      DNA array expression analysis, expand our knowledge of the molecular pathogenesis
      of this disease and may help to develop specific diagnostic, prognostic and
      therapeutic tools. However, until long-term studies examine the safety and
      efficacy of certain genetic markers, long-term follow-up of patients with CP who
      harbour mutations is needed.

PMID- 18332991
TI  - Pancreatic carcinomas smaller than 3.0 cm: endosonography (EUS) in diagnosis,
      staging and prediction of resectability.
AB  - BACKGROUND: The size of a pancreatic carcinoma determines prognosis and
      resection. The aim of this study was to review our clinical experience with
      endoscopic ultrasound (EUS) in diagnosing and staging pancreatic tumours <3.0 in
      diameter. METHODS: From February 1997 to October 2000 medical records and results
      of abdominal ultrasound (US), spiral computed tomography (CT) and EUS with fine
      needle aspiration biopsy (FNA) were reviewed in 17 patients operated for
      histologically proven pancreatic adenocarcinoma measuring <or= 3.0 cm in
      diameter. The mean age of the patients was 64 years (range 42-76 years). RESULTS:
      US identified a pancreatic lesion in 11/17 (65%) patients. Spiral CT showed a
      total of 16/17 (94%) patients with a lesion. EUS identified pancreatic tumour in
      all patients (100%), and tissue was obtained from 15/17 patients (88%). Mean
      tumour size was 2.5 cm (range 0.8-3.0 cm). EUS accuracy in evaluating the portal
      vessels was 78%, superior mesenteric artery 100%, tumour stage (T) 88%, isolated
      node stage (N) 65% and combined TN staging was 53%. Regarding resectability, EUS
      sensitivity was 88%, specificity 89%, negative predictive value 89%, positive
      predictive value 88% and accuracy 88%. Besides cytological material, EUS-FNA
      histological diagnosis was possible in 12/17 patients (71%). There was only one
      case of mild post-procedure acute pancreatitis. CONCLUSION: EUS-FNA is safe and
      has high diagnostic (100%) and local staging (88%) accuracy in pancreatic cancers
      <3.0 cm in diameter.

PMID- 18332992
TI  - Mini-cholecystectomy: a personal series in acute and chronic cholecystitis.
AB  - BACKGROUND: Minimally invasive techniques in the surgical treatment of
      gallbladder disease include laparoscopic cholecystectomy (LC) and mini
      cholecystectomy (MC). Reports of LC in acute or chronic inflammation of the
      gallbladder are common, but those of MC are much more limited, particularly in
      complicated cases. METHODS: Thirty-six consecutive patients with gallstone
      disease who underwent mini-cholecystectomy (MC) were included in this study.
      Twenty-four were female, median age 62 years (range 23-82) and median body mass
      index (BMI) was 23.4 (range 17.0-28.4). Seventeen of 36 patients had an acutely
      inflamed gallbladder, one with septicaemia, and six had gangrenous cholecystitis.
      Three patients presented with acute pancreatitis. MC was performed by a
      standardised technique. Operative time, frequency of postoperative analgesic
      injections, time to start oral diet after operation and length of postoperative
      hospital stay were compared between patients with chronic and acute
      cholecystitis. RESULTS: The median operative time was 92.5 minutes (range 35
      130). There was no difference in operative time between patients with chronic and
      acute cholecystitis: 80 minutes (range 35-120) vs 95 minutes (range 60-130). The
      frequency of postoperative analgesic injections was also similar in the two
      groups. Oral diet could be started within 24 h of operation in all except one
      patient with chronic cholecystitis but in only 8 of 17 with acute cholecystitis.
      Postoperative hospital stay was shorter in patients with chronic cholecystitis: 2
      days (range 2-5) vs 4 days (range 2-14), p =0.0009. CONCLUSIONS: MC is an
      effective surgical procedure for an inflamed gallbladder regardless of the degree
      and type of inflammation. Patients with chronic cholecystitis recover more
      quickly and have a shorter hospital stay.

PMID- 18332993
TI  - Major hepatectomy for isolated metastases from gastric adenocarcinoma.
AB  - BACKGROUND: Liver metastases from gastric adenocarcinoma denote a poor prognosis.
      Most gastric metastases will be diffuse, and for these chemotherapy remains the
      only useful treatment modality. The treatment of isolated liver metastases is
      still unclear. The Japanese literature has reported good results with surgical
      resection, but Western series were unable to achieve the same results. We report
      our results with resection of liver metastases from gastric cancer in nine
      patients. METHODS: A retrospective analysis was undertaken to determine the
      results of the surgical treatment of hepatic metastases from gastric carcinoma
      over the last five decades. Only nine patients underwent such treatment.
      Variables analysed were age, gender, the primary tumour, the type of liver
      operation performed, the time of occurrence of liver metastasis, the morbidity
      and mortality and the overall survival. Follow-up was complete. RESULTS: There
      were eight patients with gastric carcinoma staged as T3 and one as T4 (UICC-97).
      All patients had positive lymph nodes. The hepatic procedure performed was a
      hemihepatectomy in eight patients and a left lateral segmentectomy in one
      patient. Right hepatectomy was performed in six cases. There were four patients
      with synchronous liver metastasis: three involved the right liver and the other
      involved segments II/III. All were treated by one-step surgery. The five
      metachronous metastases involved the right liver in three patients (accounting
      for half of the right hepatectomies), while the other two underwent left
      hepatectomies. There was a high postoperative mortality rate (33%, 3/9), two of
      the deaths occurring in the first decade of the study (1956, 1966) secondary to
      hepatic insufficiency and one from sepsis. One patient died suddenly without
      recurrence after 3 months. The other five died with evidence of disease at
      between 2 and 11 months. DISCUSSION: Despite some anecdotal reports of treatment
      with chemotherapy, either systemic or intrahepatic, the more consistent results
      for the treatment of patients with hepatic metastases from gastric adenocarcinoma
      come from the Japanese literature with the use of radical surgery. Unfortunately,
      Western series, including our own, do not achieve the same results. At the
      present time, in view of these results, we are performing less aggressive
      treatment such as radio-frequency ablation.

PMID- 18332994
TI  - AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: rationale
      and overview of the conference.

PMID- 18332995
TI  - AHPBA/AJCC consensus conference on staging of hepatocellular carcinoma: consensus
      statement.

PMID- 18332996
TI  - Embolisation of metachronous pseudoaneurysms complicating chronic pancreatitis.
AB  - BACKGROUND: Pseudoaneurysm bleeding is a well-described complication of chronic
      pancreatitis. Reports of embolisation therapy for metachronous pseudoaneurysms in
      this condition are rare. We present such a patient and describe his management.
      CASE OUTLINE: A 5 1-year-old man with chronic pancreatitis who presented with
      recurrent occult major gastrointestinal bleeding underwent angiography on two
      separate occasions, 2 years apart. Initial intervention revealed the origin of
      the coeliac axis to be occluded or absent, and a splenic artery (SA) aneurysm,
      feeding via the superior mesenteric artery, was embolised. Subsequent angiography
      after a major bleed showed a new pseudoaneurysm in the head of pancreas feeding
      from an aberrant hepatic artery, which was embolised. The second angiogram
      confirmed persistent occlusion of the SA aneurysm and 6 months follow-up showed
      no evidence of recurrence of the second aneurysm. DISCUSSION: The resolution of
      these metachronous pseudoaneurysms by angiographic embolisation attests to the
      validity of this approach as potentially definitive and repeatable therapy.

PMID- 18332997
TI  - A salvage treatment for solid liver metastasis after radical resection of
      Klatskin tumour.
AB  - BACKGROUND: Long-term survival has not been described following surgical
      resection for liver metastasis after radical resection of an advanced hilar bile
      duct carcinoma (Klatskin tumour). One such patient who developed liver metastasis
      after radical treatment for stage IVA (pTNM) hilar cholangiocarcinoma has
      survived 5.5 years after resection of the liver metastasis followed by
      chemotherapy. CASE REPORT: A 50-year-old man developed a solid liver metastasis
      in segment VIII 17 months after radical resection of a stage IVA (pT3 pN I MO)
      Klatskin tumour followed by postoperative radiotherapy (54 Gy) and systemic
      chemotherapy (oral UFT 450 mg/day plus intravenous cisplatin 20 mg on 5
      consecutive days each month). The patient is alive at 7 years after the primary
      resection followed by resection of the liver metastasis plus further systemic
      chemotherapy comprising oral UFT combined with intravenous adriamycin (ADM) and
      mitomycin C (MMC). CONCLUSION: Aggressive salvage resection surgery can be an
      effective component of a multidisciplinary treatment regimen, even for a
      postoperative liver metastasis that developed after radical resection of an
      advanced Klatskin tumour, provided that the metastasis is solid and has not
      failed local-regional control.

PMID- 18332998
TI  - Disseminated bony metastases following incidental gallbladder cancer detected
      after laparoscopic cholecystectomy.
AB  - BACKGROUND: In patients with gallbladder cancer bony metastases are usually a
      late feature. CASE OUTLINE: A 47-year-old woman presented with a 2-month history
      of right upper quadrant pain. Ultrasound scan showed gallstones and a thick
      walled gallbladder. Laparoscopic cholecystectomy was performed. Histopathology
      showed poorly differentiated adenocarcinoma infiltrating the muscular layer and
      vascular invasion. She was referred for further surgery. Staging CT scan of the
      abdomen showed no local residual disease. However Tc-99 bone scan suggested
      disseminated bony metastases, which were confirmed by bone trephine biopsy. The
      cancer progressed rapidly and the patient died 4 months after the diagnosis.
      DISCUSSION: Bone metastases can occur with early gallbladder cancer and a
      radioisotope bone scan can avoid unnecessary extensive liver surgery.

PMID- 18332999
TI  - A case of cholecystohepatic duct with atrophic common hepatic duct.
AB  - BACKGROUND: Cholecystohepatic ducts are rare congenital variants of the biliary
      tree. CASE OUTLINE: An 81-year-old woman presented with biliary colic and
      elevated liver function tests. An ERCP demonstrated a common bile duct stone and
      stricture of the common hepatic duct. An operative cholangiogram demonstrated an
      atrophic common hepatic duct and retrograde filling of the gallbladder through a
      large cholecystoheptic duct. The patient had a cholecystectomy and reconstructive
      cholecystohepatic duct jejunostomy. DISCUSSION: This case demonstrates a rare
      congenital anomaly where the gallbladder fills retrograde during an
      intraoperative cholangiogram despite clipping of the cystic duct. The major path
      of biliary drainage was through a large cholecystoheptic duct similar to a
      gallbladder interposition; however, the common hepatic duct was still present but
      atrophic. This anomaly has not been described previously.

PMID- 18333000
TI  - Management of a solid pseudopapillary tumor of the pancreas with liver
      metastases.
AB  - BACKGROUND: Solid pseudopapillary tumor, otherwise known as solid and cystic
      tumor or Frantz tumor, is an unusual form of pancreatic carcinoma. Its natural
      history differs from the more common pancreatic adenocarcinoma in that it has a
      female predilection, is more indolent, and carries a better prognosis. Metastatic
      disease can occur, usually involving the liver, and its management is not well
      defined. CASE OUTLINE: A young woman was found to have a tumor situated in the
      pancreatic tail with seven synchronous hepatic metastases. Segments II and III
      were free of metastatic disease. A needle biopsy of the pancreatic lesion was non
      diagnostic but suggested that the lesion was unlikely to be a typical
      adenocarcinoma. Initial treatment consisted of a distal pancreatectomy, which
      confirmed the diagnosis of a solid pseudopapillary tumor. Given the indolent
      nature of this pathologic entity as well as the patient's youth, an aggressive
      approach to treatment of the hepatic metastases was recommended. Because the
      liver was fatty, the right portal vein was embolized to produce hypertrophy of
      the left hemiliver. Six weeks later an extended right hepatectomy cleared the
      hepatic disease. The patient had an uncomplicated recovery, and she remains
      disease-free at 22 months. DISCUSSION: Solid pseudopapillary tumor of the
      pancreas is a rare malignancy. Survival following primary resection approaches
      95% at 5 years. Metastatic disease, although rare, usually involves the liver
      and/or peritoneum. Given the paucity of reported cases, the management of
      metastatic disease is, to date, poorly defined. This case demonstrates a
      favorable short-term outcome with aggressive surgical treatment of both the
      primary and metastatic tumor.

PMID- 18333001
TI  - Sclerosing pancreatitis presenting as a periampullary tumour.
AB  - BACKGROUND: Sclerosing lesions of the pancreatic duct are rare and may be
      secondary to primary sclerosing cholangitis (PSC) or the result of a primary
      sclerosing process (the recently described lymphoplasmacystic sclerosing
      pancreatitis, LSP). Occasionally this process may present as a mass lesion. CASE
      OUTLINE: A 21 -year-old man presented with abdominal pain and jaundice, giving a
      high index of suspicion for a periampullary malignancy. There were minimal
      symptoms suggestive of PSC. The resected head of the pancreas demonstrated
      changes of chronic pancreatitis with a fibro-inflammatory process of the
      pancreatic duct suggesting an underlying ductal sclerosing process. DISCUSSION:
      Clinical presentation and imaging characteristics of PSC involving the pancreas
      are often misleading and may suggest a neoplasm as the underlying disorder.
      Conclusive diagnosis is usually not determined until after surgical intervention.
      Although racial differences in pancreatic duct involvement have been suggested,
      the underlying histopathology is the same as in PSC involving the biliary ducts.

PMID- 18333002
TI  - Presentation.

PMID- 18333003
TI  - Free papers.

PMID- 18333006
TI  - Fracture of the pancreas in two patients after a go-kart accident.
AB  - BACKGROUND: After blunt abdominal trauma, an isolated injury to the pancreatic
      duct is uncommon. Physical signs and laboratory parameters are often inaccurate,
      and missing this diagnosis can cause serious clinical problems. CASE OUTLINES:
      Two young women (aged 18 and 20 years) are reported who sustained isolated trauma
      to the pancreatic duct in go-kart accidents. Each patient sustained a fracture of
      the pancreas.This injury was diagnosed only after a period of clinical
      observation with repeated laboratory parameters, ultrasound and CT scan.
      Pancreatic tissue was conserved by performing a pancreaticojejunostomy.
      DISCUSSION: After any episode of blunt abdominal trauma, isolated injury to the
      pancreatic duct should be considered. Serum analysis, ultrasonography and CT
      scanning can be helpful in early diagnosis. Preservation of pancreatic tissue can
      be achieved with a good clinical outcome.

PMID- 18333007
TI  - Mixed (composite) glandular-endocrine cell carcinoma of the gallbladder.
AB  - BACKGROUND: A mixed pattern of glandular and neuroendocrine elements is rare in
      tumours at any site within the gastrointestinal tract but particularly so in the
      gallbladder. CASE OUTLINE: A 72-year-old woman presented with abdominal pain and
      jaundice and was found to have a large mass in the fundus of the gallbladder.The
      mass was radically excised to include a wedge of liver and the hepatoduodenal
      lymph nodes. Histopathological examination of the resected gallbladder showed an
      invasive tumour composed of both adenocarcinoma and endocrine cell carcinoma,
      with apparent transitions between them. The patient received no further treatment
      and died two months later. DISCUSSION: There are 14 previous case reports of
      mixed adeno/endocrine carcinoma of the gallbladder. Histochemical similarities
      between the two neoplastic components of the present tumour would support their
      origin from a common precursor cell, but the alternative hypothesis of
      coincidental neoplastic change in two different cell types cannot be excluded.

PMID- 18333008
TI  - Hepatic resection for primary giant leiomyoma of the liver.
AB  - BACKGROUND: Smooth muscle tumours are common in the genito-urinary and gastro
      intestinal tracts, but primary leiomyoma of the liver is extremely rare. Only a
      few cases have been reported to date. CASE OUTLINE: We report a case of giant
      leiomyoma of the liver in a 67-year-old woman that was treated by an extended
      right hepatectomy. There was no evidence of leiomyoma elsewhere in the abdomen
      (including the uterus). DISCUSSION: This appears to be the largest hepatic
      leiomyoma reported in the literature.

PMID- 18333013
TI  - Biliary malignancies: modest gains, residual strains.

PMID- 18333009
TI  - Intracystic arteries in a chronic pancreatic pseudocyst.
AB  - BACKGROUND: An enlarging pancreatic pseudocyst can incorporate adjacent vessels
      into its wall, leading to pseudoaneurysm formation in the presence of proteolytic
      enzymes. Intact arteries running through the cyst cavity are very rare, however.
      CASE OUTLINE: A 54-year-old man with a chronic pancreatic pseudocyst (15 cm
      diameter) underwent internal drainage by means of cystjejunostomy Roux-en-Y. Two
      large pulsating arteries running through the cyst cavity were identified as the
      middle colic artery and one of its branches. Temporary clamping of the
      transcystic arteries revealed no signs of ischaemia in the transverse colon, so
      the vessels were ligated and the cystjejunostomy completed. The patient remains
      well one year later. DISCUSSION: Bleeding following internal drainage procedures
      carries a higher mortality rate than spontaneous bleeding in chronic pancreatic
      pseudocysts but is easier to prevent.This case highlights the importance of
      thorough exploration of the pseudocyst to identify any vessels in its cavity or
      wall.

PMID- 18333014
TI  - Quality control in laparoscopic cholecystectomy: operation notes, video or photo
      print?
AB  - BACKGROUND: In 1995 the concept of a 'critical view of safety' (CVS) in Calot's
      triangle was introduced to prevent bile duct injury in laparoscopic
      cholecystectomy. The aim of this study was to determine the most reliable method
      for recording CVS. METHODS: Operation notes, video images and photo prints from
      50 consecutive elective non-converted laparoscopic cholecystectomies were
      analysed. RESULTS: Operation notes alone did not suffice to record CVS. As an
      adjunct, video proved superior to photo print with regard to quality.
      Nevertheless, photo prints were practically and logistically much easier to
      produce than video. Moreover, when good quality images were achieved, photo print
      recorded CVS more conclusively than video. DISCUSSION: Operation notes,video and
      photo print are complementary, and the combination records CVS conclusively in
      nearly every case.

PMID- 18333015
TI  - Pyogenic liver abscesses: a comparison of older and younger patients.
AB  - BACKGROUND: Pyogenic liver abscess is a life-threatening disease. Few studies
      have specifically explored the way in which the clinical features and management
      of elderly patients with pyogenic liver abscess differ from those of younger
      individuals. METHODS: A retrospective study was undertaken to evaluate whether
      older patients with pyogenic liver abscess have distinctive presenting features
      or whether their management and outcome differ from that of younger patients. A
      total of 133 patients with liver abscess treated in five hospitals during 13
      years comprised two groups: 78 patients aged 60 years or above (older group) and
      55 patients below age 60 years (younger group). Clinical features, laboratory
      data, imaging and microbiological findings, management and outcome were
      determined in each group. RESULTS: The older group contained more patients with
      associated diseases (p=0.03), nausea and vomiting at presentation (p=0.02),
      higher APACHE II (Acute Physiological and Chronic Health Evaluation II scale)
      score (p<0.001) and blood urea nitrogen (p<0.001) and serum creatinine levels
      (p=0.002). Multiple abscess (p=0.05) and bilobar (p=0.03) abscess were also
      commoner in this group. By contrast, in the younger group men predominated
      (p=0.01), and there was a higher overall complication rate (p=0.05).Time to
      diagnosis, hospital mortality rate and other variables analysed were similar in
      both groups. DISCUSSION: Elderly patients with pyogenic liver abscess have some
      subtle differences in clinical and laboratory presentation, but these do not
      appear to delay diagnosis. Active management is tolerated well, with a lower
      morbidity rate than in younger patients and no difference in the mortality rate.

PMID- 18333016
TI  - Laparoscopic peritoneal lavage cytology and immunocytology in pancreatic and
      periampullary carcinoma.
AB  - BACKGROUND: Free tumour cells in the peritoneal cavity of patients with
      pancreatic carcinoma carry a poor prognosis. Reactive or degenerative mesothelial
      cells can make cytological interpretation with conventional stains difficult.
      Detection of the tumour-associated antigens carcinoembryonic antigen (CEA) and
      CA19-9 may improve detection. METHODS: At staging laparoscopy, 22 patients with
      pancreatic or periampullary tumours had ascitic fluid aspirated or peritoneal
      lavage performed. Both conventional and immunocytologically stained preparations
      were examined. Antibodies to CEA and CA19-9 and the epithelial marker BerEP4 were
      used. Lavage fluid from ten patients having operative treatment for benign
      pancreatic or biliary conditions was also examined. RESULTS: No malignant cells
      on conventional cytological criteria were recovered.Thirteen of the 22 patients
      with pancreatic or periampullary carcinoma had peritoneal cells that were
      positive for CEA and/or CA19-9. None was positive for BerEP4. No patients with
      resectable disease had cells that were positive for CEA or CA19-9 compared with
      13 of 18 (72%) who had unresectable disease. One patient (10%) with benign
      disease (chronic pancreatitis) had cells recovered that were weakly positive for
      CEA but negative for CA19-9 and BerEP4. DISCUSSION: Recovery of cells from the
      peritoneal cavity of patients with pancreatic or periampullary carcinoma that are
      expressing the tumour-associated antigens CEA or CA19-9 does not indicate the
      presence of free tumour cells but is associated with advanced disease.

PMID- 18333017
TI  - Differences in tumour growth, tumour cell proliferation and immune function after
      laparoscopy and laparotomy in an animal model.
AB  - BACKGROUND: Clinical and experimental studies have shown that laparoscopy
      preserves the immune response and can give better clinical results than
      laparotomy. However, the use of laparoscopy for the treatment of cancer patients
      is still controversial due to the risk of port-site and haematogenous metastases
      and increased tumour growth. The purpose of this experimental study was to assess
      tumour growth and the mechanism of differential tumour behaviour after
      laparoscopy and laparotomy. METHODS: Seventy-five young, male Wistar rats were
      randomly assigned to one of two experiments. Experiment 1: 45 animals were
      inoculated subcutaneously with Walker carcinosarcoma 256 cells and were
      subdivided into three groups of 15 rats. Control group la was submitted to
      anaesthesia only, group 1b received carbon dioxide (CO(2)) pneumoperitoneum,while
      group 1c received a laparotomy. Animals were sacrificed on postoperative day
      (POD) 7; tumours were excised and weighed to evaluate tumour growth. Nucleolar
      organiser regions identified by silver staining (AgNORs) were analysed to
      evaluate cell proliferation. Experiment 2: 30 rats were submitted to the same
      procedures as before, with ten animals in each group (2a, 2b, 2c), and a delayed
      type hypersensitivity response (DTH) was used to evaluate the immune function.
      RESULTS: The average tumour mass was 1.76 g in group 1a, 2.81 g in group 1b and
      4.21 g in group 1c (p < 0.05). The AgNOR expression results were similar in the
      three groups. The immune function was better preserved in the control group (2a:
      average inflammatory area on POD1 = 106 mm(2) and on POD2 = 128.18 mm(2)), than
      in the pneumoperitoneum group (2b: average inflammatory area on POD1 = 79.75
      mm(2) and on POD2 = 126.93 mm(2)); the worst results were in the laparotomy group
      (2c: average inflammatory area on POD1 = 33.33 mm(2) and on POD2 = 61.32
      mm(2)).There were significant differences between groups 2a and 2c and between 2b
      and 2c. CONCLUSION: Laparotomy stimulates a greater tumour growth than CO(2)
      pneumoperitoneum, but there is no difference in tumour cell proliferation. The
      cellular immune function is better preserved in animals submitted to CO
      pneumoperitoneum than in the laparotomized animals. These results suggest a
      relationship between a weaker immune response and a greater tumour growth.

PMID- 18333018
TI  - Philip Sandblom; surgeon, scientist, humanist and citizen of the world (1903
      2001).

PMID- 18333019
TI  - Parathyroid hormone-related peptide in pancreatic neuroendocrine tumours
      associated with hypercalcaemia.
AB  - BACKGROUND: Hypercalcaemia is a common paraneoplastic syndrome. In the context of
      pancreatic neuroendocrine tumours, it is occasionally caused by secretion of
      parathyroid hormone-related peptide (PTH-rP). CASE OUTLINES: Two patients are
      reported in whom persistent hypercalcaemia was traced to a large neuroendocrine
      pancreatic tumour hypersecreting PTH-rP. Resection of the tumour reduced serum
      levels of calcium and PTH-rP transiently in each case until the patient developed
      bulky metastatic disease. A 33-year-old woman remained hypercalcaemic after the
      removal of all four hyperplastic parathyroid glands had rendered circulating
      parathormone levels undetectable. Radical distal pancreatectomy was followed over
      the next 4 years by operative debulking of liver metastases, multiple hepatic
      artery embolisations, octreotide injections and repeated admissions for
      intravenous fluid and biphosphonate therapy. A 41-year-old man presented with
      hypercalcaemia as well as features of somatostatinoma syndrome. Symptomatic
      improvement after radical distal pancreatectomy was short-lived, and hepatic
      artery embolisation failed to control his rapidly progressive disease.
      DISCUSSION: Malignant hypercalcaemia associated with a neuroendocrine pancreatic
      tumour hypersecreting PTH-rP is difficult to treat and can be life-threatening.
      Aggressive surgical treatment is recommended initially, while somatostatin
      analogues and hepatic artery embolisation are alternative therapeutic options for
      metastatic disease.

PMID- 18333020
TI  - Spontaneous rupture of hepatocellular carcinoma with haemoperitoneum: a rare
      condition in Western countries.
AB  - BACKGROUND: Haemoperitoneum secondary to non-traumatic liver rupture is a rare
      but potentially fatal condition. It may result from several neoplastic and non
      neoplastic diseases such as primary benign or malignant tumours, peliosis
      hepatis, polyarteritis nodosa, systemic lupus erythematosus, pre-eclampsia and
      metastatic carcinoma. CASE OUTLINES: Three cases of spontaneous haemoperitoneum
      caused by rupture of hepatocellular carcinoma are described. All three patients
      (two men, one woman) had cirrhotic livers, and all were submitted to an urgent
      operation.One patient re-bled on a second occasion. Emergency operation was
      undertaken four times in three patients and was successful on all but one
      occasion. DISCUSSION: The prognosis for patients with haemoperitoneum is
      generally poor. Although this condition is relatively frequent in some regions of
      Asia and Africa, it has rarely been reported in Western countries.The present
      experience shows that emergency laparotomy can be life-saving.

PMID- 18333021
TI  - Initial failure of angiography to demonstrate a bleeding pancreatic cancer: a
      case for provocative agents.
AB  - BACKGROUND: Mesenteric angiography is commonly employed in the modern-day
      investigation of gastro-intestinal bleeding if the bleeding sites cannot be
      identified by endoscopic means. Angiography is optimally sensitive in the
      presence of active bleeding. However, vasospasm may occasionally account for a
      negative study shortly after bleeding. CASE OUTLINE: A 70-year-old lady with
      inoperable carcinoma of the pancreas presented with gastro-intestinal bleeding.
      Although upper endoscopy visualised active bleeding from the tumour, which had
      invaded into the duodenum, haemostasis could not be achieved endoscopically.
      Therefore, mesenteric angiography was arranged. RESULTS: The initial angiography
      failed to demonstrate the bleeding site, which only became obvious on a repeat
      study, when embolisation was performed to achieve haemostasis. DISCUSSION:
      Vasospasm probably accounted for the initial negative study, as the second
      angiography was able to demonstrate contrast extravasation without the use of any
      anticoagulant or thrombolytic agent. It is not our routine to give
      pharmacological agents to provoke bleeding after a negative angiography, but for
      selected patients this manoeuvre may turn out to be more cost-effective.

PMID- 18333022
TI  - Eosinophilic cholangitis: a case of 'malignant masquerade'.
AB  - BACKGROUND: A variety of causes of inflammatory bile duct stricture can
      masquerade as hilar cholangiocarcinoma. Eosinophilic cholangitis is a further
      example. CASE OUTLINE: A 50-year-old woman with epigastric pain and deranged
      liver function was found to have a stricture of the common hepatic duct on ERCP
      with an associated mass on MRl.The lesion was excised with reconstruction of the
      right and left hepatic ducts, and the patient recovered well. Histopathological
      examination of the resected gallbladder and bile duct showed diffuse inflammation
      with a predominant eosinophil infiltrate.The presence of Candida albicans in the
      bile duct lumen can probably be attributed to the preoperative biliary
      stent.There was a modest postoperative rise in peripheral eosinophil count.
      DISCUSSION: A literature search reveals only six previous cases of eosinophilic
      cholangitis, but similar infiltrates have also been seen in occasional
      cholecystectomy specimens. As the present patient did not have gallstones, the
      aetiology remains unclear. Peripheral eosinophilia is an unreliable clue to the
      diagnosis, which is usually likely to escape detection until the biliary
      stricture has been resected.

PMID- 18333023
TI  - Successful repair of Bismuth type 2 bile duct stricture by T-tube stented
      omentoplasty: 19 years follow-up.
AB  - BACKGROUND: The 'gold standard' of surgical repair of extrahepatic bile duct
      strictures is hepaticojejunostomy (HJ). This is a proven procedure with the
      drawback of a nonanatomic bile duct drainage by passing the ampullary sphincter
      system. On theoretical grounds an anatomical reconstruction would be desirable.
      CASE OUTLINE: This case demonstrates the possibility of repairing a Bismuth type
      2 stricture with a longitudinal incision and a T-tube stented omentoplasty. After
      a follow-up of 19 years, the reconstruction rendered an anatomically and
      physiologically normal repair. DISCUSSION: Stented omentoplasty may be an
      alternative to HJ in Bismuth type 1 and 2 lesions.The success of this unorthodox
      repair technique does not warrant a general recommendation at this stage,
      however. Pertinent analogous literature reports are scarce, and the evidence base
      is very limited.The case report is rather intended as an incentive for further
      research outlining the possibilities and limitations of this technique.

PMID- 18333026
TI  - Results of laparoscopic splenectomy for treatment of malignant conditions.
AB  - BACKGROUND: Laparoscopic splenectomy (LS) is widely accepted for treatment of
      benign diseases, but there are few reports of its use in cases of haematological
      malignancy. In addition, comparative studies with open operation are lacking.
      Malignant haematological diseases have specific clinical features-notably
      splenomegaly and impaired general health-which can impact on the immediate
      outcome after LS. The immediate outcome of LS comparing benign with malignant
      diagnoses has been analysed in a prospective series of 137 operations. PATIENTS
      AND METHODS: Between February 1993 and April 2000, 137 patients with a wide range
      of splenic disorders received LS. Clinical data and immediate outcome were
      prospectively recorded,and age, diagnosis, operation time, perioperative
      transfusion requirement, spleen weight, conversion rate, accessory incision,
      hospital stay and complications were analysed. RESULTS: The series included 100
      benign cases and 37 suspected malignancies. In patients with malignant diseases
      the mean age was greater (37 years [3-85] vs 60 years [27-82], p<0.01), LS took
      longer (138 min [60-400] vs 161 min [75-300], p<0.05) and an accessory incision
      for spleen retrieval was required more frequently (18% vs 93%, p<0.01) because
      the spleen was larger (279 g [60-1640] vs 1210 g [248-3100], p <0.01). However,
      the rate of conversion to open operation (5% vs 14%), postoperative morbidity
      rate (13% vs 22%) and transfusion requirement (15% vs 26%) did not differ between
      benign and malignant cases. Hospital stay was longer in malignant cases (3.7 days
      [2-14] vs 5 days [2-14], p<0.05). CONCLUSION: LS is a safe procedure in patients
      with malignant disease requiring splenectomy in spite of the longer operative
      time and the higher conversion rate.

PMID- 18333027
TI  - Total pancreatectomy in six patients with intraductal papillary mucinous tumour
      of the pancreas: the treatment of choice.
AB  - BACKGROUND: Intraductal papillary mucinous tumours (IPMT) were described as a
      distinct entity in 1982.The extent of surgical resection remains controversial.
      METHODS: Six patients with a diffuse dilatation of the main pancreatic duct were
      treated with total pancreatectomy for cure of IPMT. RESULTS: Histological
      examination showed one IPM adenoma, four IPM non-invasive carcinomas and one IPM
      invasive carcinoma. In all but one case multifocal extensive intraductal changes
      were found, affecting either most of the pancreas or the whole organ. All
      patients survived the operation and remain alive 5-56 months later. Post
      pancreatectomy diabetes has been moderately well controlled. DISCUSSION: IPMTs
      represent a subgroup of pancreatic neoplasms with a favourable prognosis, and the
      resection should aim at removing all dysplastic foci. In cases with diffuse
      dilatation of the main pancreatic duct, widespread tumour involvement of the duct
      system can be expected, so total pancreatectomy should be the operation of
      choice.

PMID- 18333028
TI  - Surgically transplanted ovary simulating a hepatic metastasis.
AB  - BACKGROUND: Surgical procedures may alter normal anatomy, confounding the
      interpretation of cross-sectional imaging studies. This problem is greater if
      neither a relevant history nor previous comparison studies are available. CASE
      OUTLINE: In a 29-year-old woman submitted to radical hysterectomy for cervical
      carcinoma, one ovary was surgically repositioned into the right paracolic gutter
      out of the radiation field. This ovary simulated a hepatic metastasis on
      subsequent CT examinations. History was obscure, adding to the interpretive
      challenge. DISCUSSION: Clues to establishing the correct diagnosis are presented.
      The availability of an adequate history and previous radiological images are
      important to prevent diagnostic error.

PMID- 18333029
TI  - Synchronous bleeding of liver adenomatosis and possible relation to acoustic
      trauma.
AB  - BACKGROUND: Solitary hepatic adenoma is a rare tumour but adenomatosis of the
      liver is even less common; it has been defined arbitrarily as more than four
      adenomas within otherwise normal hepatic parenchyma. Usually asymptomatic, the
      main clinical presentation is abdominal pain secondary to bleeding from the
      tumour. CASE OUTLINE: A 40-year-old woman admitted for abdominal pain and
      operated within a few hours due to circulatory instability was found to have
      synchronous bleeding from three out of four liver cell adenomas. The onset of
      pain followed shortly after exposure to particularly loud music. The three
      bleeding tumours were enucleated. The fourth lesion was left in situ; during
      outpatient follow-up it decreased in size and eventually disappeared. DISCUSSION:
      Although rupture with bleeding is a well-known presentation of liver cell
      adenomas, synchronous bleeding from more than one tumour is exceedingly uncommon
      and this may be the first reported case. Enucleation of the tumour is easy to
      perform even during active bleeding. Small asymptomatic tumours may be followed
      without surgical intervention.

PMID- 18333030
TI  - Mucinous cystic tumour of the pancreas presenting with acute pancreatitis.
AB  - BACKGROUND: The optimal therapy for mucinous neoplasms of the pancreas is
      surgical resection because these tumours are either premalignant (cystadenoma) or
      malignant. CASE OUTLINE: A 44-year-old previously fit woman presented with sudden
      onset of epigastric pain. Clinical and laboratory findings were consistent with
      acute pancreatitis. Abdominal ultrasound scan demonstrated a mature 6-cm cyst in
      the tail of pancreas and no findings suggestive of cholelithiasis. These findings
      were confirmed by a CT scan, which also demonstrated splenic infarction and
      evidence of recent haemorrhage into the cyst. The patient's abdominal pain
      persisted after amylase levels returned to normal. RESULTS: Splenic infarction, a
      mature cyst in the tail of the pancreas, and peripancreatic inflammation
      consistent with recent pancreatitis were found at laparotomy. Enbloc distal
      pancreatectomy and splenectomy were performed. Histological examination of the
      cyst wall demonstrated a focus of mucinous cystadenoma. DISCUSSION: This case
      demonstrates that acute pancreatitis may be the first presentation of a cystic
      neoplasm.

PMID- 18333031
TI  - A complication of infrarenal arterial conduit following orthotopic liver
      transplant.
AB  - BACKGROUND: Thrombosis of the arterial inflow to a transplanted liver graft
      frequently leads to graft necrosis, and retransplantation is required. CASE
      OUTLINE: A 41-year-old man underwent orthotopic liver retransplantation. Arterial
      inflow to the graft was provided by an infrarenal arterial conduit. On day 14 he
      developed thrombosis of the conduit due to herniation of the jejunum between the
      conduit and the transverse mesocolon. Reduction of the herniated bowel and
      thrombectomy of the graft was initially successful, but he subsequently developed
      necrosis of segments II-V (diagnosed on computed tomography, CT). These segments
      were then resected, and thereafter his graft functioned well over the next 7
      years. DISCUSSION: The potential space between an infrarenal arterial conduit and
      the transverse mesocolon must be eliminated to prevent incarceration of the
      intestine following liver transplantation. Early diagnosis of arterial thrombosis
      may allow revascularisation of the liver graft, but subsequent CT scanning is
      essential to assess the viability of the graft. Segmental graft necrosis may be
      managed by liver resection with good long-term results.

PMID- 18333032
TI  - Spontaneous cholecystocutaneous fistula.
AB  - BACKGROUND: An external biliary fistula is a rare complication of gallstone
      disease. We present a case of cholecystocutaneous fistula successfully treated
      with excision and cholecystectomy. CASE OUTLINE: A 67-year-old man presented with
      a persisting discharge from what was thought to be an'abscess' in the right
      hypochondrium, which had previously been incised and drained. RESULTS:
      Investigation with computed tomography, ultrasound scanning and sinography
      demonstrated a cholecystocutaneous fistula and calculous cholecystitis. The
      fistulous track was excised together with the gallbladder. DISCUSSION: This
      condition is rarely seen nowadays due to the greater availability of antibiotic
      therapy and biliary surgery. Cholecystectomy is the preferred treatment, although
      in a few patients, the fistula may close spontaneously.

PMID- 18333033
TI  - Papillary cystic neoplasm of the pancreas.
AB  - BACKGROUND: Papillary cystic neoplasm of the pancreas is a rare disorder that
      occurs most commonly in young women. It has a low potential for malignancy, and
      the prognosis following resection is favourable. CASE OUTLINE: An 18-year-old
      white girl presented with a palpable mass in the right hypochondrium on physical
      examination associated with epigastric pain, nausea and vomiting, but no fever.
      Upper gastro-intestinal endoscopy revealed extrinsic compression of the posterior
      wall of the antrum and duodenal bulb with no mucosal lesion. Computed tomography
      (CT) scan and then laparotomy revealed a large tumour adjacent to the hepatic
      hilum and originating from the head of pancreas. Pancreatoduodenectomy was
      performed, and a diagnosis of papillary cystic neoplasm of the pancreas was
      made.There was no evidence of recurrence after 6 years of follow-up. DISCUSSION:
      A radical surgical approach is justified for papillary cystic neoplasm of the
      pancreas because of its biological behaviour, local aggressiveness and low
      incidence of metastases.

PMID- 18333034
TI  - Spontaneous perforation of the bile duct.
AB  - BACKGROUND: Spontaneous perforation of the bile ducts is a rare condition in
      adults. It is commonly secondary to gallstones, and the site of the perforation
      is nearly always extrahepatic. Intrahepatic perforation has only once been
      described in the literature to date. CASE OUTLINE: We report an unusual
      presentation of this condition with perforation occurring at an intrahepatic
      site. The management of perforation and the possible predisposing factors are
      described. DISCUSSION: Adequate management of this problem requires an awareness
      of its existence and prompt, appropriate investigation to discover the cause and
      site of perforation.

PMID- 18333037
TI  - Preoperative staging and evaluation of resectability in pancreatic ductal
      adenocarcinoma.
AB  - BACKGROUND: Cancer of the pancreas is a common disease, but the large majority of
      patients have tumours that are irresectable at the time of diagnosis. Moreover,
      patients whose tumours are clearly beyond surgical cure are best treated non
      operatively, if possible, by relief of biliary obstruction and percutaneous
      biopsy to confirm the diagnosis and then consideration of oncological treatment,
      notably chemotherapy. These facts underline the importance of a standard protocol
      for the preoperative determination of operability (is it worth operating?) and
      resectability (is there a chance that the tumour can be removed?). Recent years
      have seen the advent of many new techniques, both radiological and endoscopic,
      for the diagnosis and staging of pancreatic cancer. It would be impracticable in
      time and cost to submit every patient to every test. This review will evaluate
      the available techniques and offer a possible algorithm for use in routine
      clinical practice. DISCUSSION: In deciding whether to operate with a view to
      resecting a pancreatic cancer, the surgeon must take into account factors related
      to the patient, the tumour and the institution and team entrusted with the
      patient's care. Patient-related factors include age, general health, pain and the
      presence or absence of malnutrition and an acute phase inflammatory response.
      Tumour-related factors include tumour size and evidence of spread, whether to
      adjacent organs (notably major blood vessels) or further afield. Hospital-related
      factors chiefly concern the volume of pancreatic cancer treated and thus the
      experience of the whole team. Determination of resectability is heavily dependent
      upon detailed imaging. Nowadays conventional ultrasonography can be supplemented
      by endoscopic, laparoscopic and intra-operative techniques. Computed tomography
      (CT) remains the single most useful staging modality, but MRI continues to
      improve. PET scanning may demonstrate unsuspected metastases and likewise
      laparoscopy. Diagnostic cholangiography can be performed more easily by MR
      techniques than by endoscopy, but ERCP is still valuable for preoperative biliary
      decompression in appropriate patients. The role of angiography has declined.
      Percutaneous biopsy and peritoneal cytology are not usually required in patients
      with an apparently resectable tumour. The prognostic value of tumour marker
      levels and bone marrow biopsy is yet to be established. Preoperative chemotherapy
      or chemoradiation may have a role in down-staging an irresectable tumour
      sufficiently to render it resectable. Selective use of diagnostic laparoscopy
      staging is potentially helpful in determination of resectability. Laparotomy
      remains the definitive method for determining the resectability of pancreatic
      cancer, with or without portal vein resection, and should be undertaken in
      suitable patients without clear-cut evidence of irresectability.

PMID- 18333038
TI  - Primary hepatic carcinoid tumours.
AB  - BACKGROUND: Carcinoid tumours of the liver are predominantly metastases from the
      gastrointestinal tract. Primary hepatic carcinoids are extremely rare.
      DISCUSSION: In contrast to metastases, primary hepatic carcinoids are usually
      solitary and resectable. It is important that these tumours are differentiated
      from metastases. Complete surgical resection should be contemplated and is
      generally curative.

PMID- 18333039
TI  - The measurement of liver resection margins.
AB  - BACKGROUND: All tissue shrinks to some degree when placed in formalin fixative
      solution. The degree of shrinkage of liver tissue has particular relevance to the
      measurement of resection margins, as the current recommendation is that the
      surgeon should aim to achieve a resection margin of at least 1 cm. We were unable
      to find any published data concerning shrinkage of liver tissue in formalin. The
      aim of this study was therefore to quantify the shrinkage of liver specimens in
      the fixation process. METHODS: Distances of 10, 30 and 50 mm were measured and
      marked on 18 fresh liver specimens. The specimens were then fixed in 10% formalin
      solution for 24 h, and the distances were re-measured to assess shrinkage.
      RESULTS: The observed shrinkage at all three distances was <10% after 24 h in
      formalin. The degree of shrinkage was statistically significant. CONCLUSION:
      Although the degree of shrinkage is small, it may be important when considering
      resection margins of the order of 1 cm and should therefore be taken into
      account.

PMID- 18333040
TI  - Three cases of small hepatocellular carcinoma presenting as obstructive jaundice.
AB  - BACKGROUND: Despite improved diagnostic tools, it is often difficult to make a
      correct diagnosis of small hepatocellular carcinoma (HCC) in patients with
      obstructive jaundice. CASE OUTLINES: Three cases of small HCC (<2 cm diameter)
      presenting as obstructive jaundice are reported. All tumours were initially
      diagnosed as hilar cholangiocarcinoma based on ultrasonography, computed
      tomography, cholangiography and angiography. Because of insufficient hepatic
      function, none of the patients underwent hepatic resection. One patient died 8
      months after first admission to our hospital, another died of disseminated
      intravascular coagulation I month after admission, and the third was treated with
      hepatic arterial infusion chemotherapy and survived >36 months. CONCLUSION: It is
      important to consider HCC in the diagnosis of obstructive jaundice in patients
      who are predisposed to HCC because of liver cirrhosis and/or chronic viral
      hepatitis, and have elevated serum alpha-fetoprotein.

PMID- 18333041
TI  - Hepatic adenomas in male patients.
AB  - BACKGROUND: Hepatic adenomas are benign tumours of the liver most commonly seen
      in premenopausal women. However, it is now clear that adenomas may occur in
      males. This small series reviews the characteristics of hepatic adenomas in
      males. CASE OUTLINES: Three cases of solitary hepatic adenoma occurring in
      otherwise well male patients (age 22-48 years) are presented. Two patients
      presented with abnormal liver function tests while one presented with abdominal
      pain. Imaging of the lesions demonstrated typical appearances of hepatocellular
      adenoma, resection was undertaken in all cases and all patients remain alive and
      well. DISCUSSION: Up to 20% of adenomas are documented as occurring in male
      patients. Most are solitary and occur in patients without recognised risk factors
      (steroid therapy and glycogen storage diseases types I and III). However,
      multiple adenomas are most commonly seen in male patients with risk factors. The
      imaging characteristics and presentation of adenomas in males are similar to
      female patients and, most importantly, intraperitoneal rupture and malignant
      transformation are documented in untreated adenomas in males.

PMID- 18333042
TI  - The frequency of live bacteria in gallstones.
AB  - BACKGROUND: Septic complications reported from stones and concretions lost in the
      peritoneal cavity following laparoscopic cholecystectomy reflect the infective
      potential of gallstones. Although bacteria have been demonstrated in the core of
      gallstones by scanning electron microscopy and molecular genetic techniques,
      gallstone culture is the only conclusive proof of whether such bacteria are
      viable and can cause infection. METHODS: Gallstones retrieved from patients
      undergoing cholecystectomy were decontaminated after surface cleaning with
      alcohol, and each core was scooped for culture. RESULTS: In this study organisms
      were cultured from the cores of gallstones in 81% of cases of cholelithiasis and
      77% of cases of gallbladder carcinoma, irrespective of stone type and size. Both
      enteric (57.5%) and non-enteric (20%) organisms were isolated in cholelithiasis,
      whereas only enteric bacteria could be cultured from cases of gallbladder
      carcinoma. Long thought to be a causative agent, Salmonella organisms were
      detected in none of the 14 cases of gallbladder carcinoma. CONCLUSION: Contrary
      to the popular belief that bacteria inside gallstones are dead, gallstones from
      most patients contain live bacteria with the potential to cause infective
      complications.

PMID- 18333043
TI  - A new method to establish the rational extent of hepatic resection for advanced
      gallbladder cancer using dye injection through the cystic artery.
AB  - BACKGROUND: Hepatic resection has been indicated to eliminate cancer at the
      surgical margin in cases of advanced gallbladder carcinoma, but there is
      considerable controversy about the reasonable extent of liver resection. A new on
      table dye injection technique has been introduced to determine the venous
      drainage of the gallbladder and ascertain the amount of liver to remove. METHODS:
      In four hepatic resections for pT2 gallbladder cancer, indocyanine green solution
      (25 mg/20 ml) was injected over a period of 30 seconds through the cystic artery.
      The stained area of the liver surface was completely resected, maintaining a
      margin of at least 2 cm from the gallbladder. RESULTS: The entire serosal surface
      of the gallbladder takes on a light green stain immediately after dye injection,
      and then the liver surface around the gallbladder gradually becomes stained with
      a clear demarcation line. The distance between the demarcation line and the
      gallbladder ranged from 1.0 to 5.0 cm. The extent of the stained area differed
      from one individual to another. Histopathological examination of resected liver
      specimens revealed that one of the four resected livers had micrometastasis in
      the portal area 27 mm from the gallbladder wall and there were no cancer cells at
      the surgical margins. No recurrence has been seen in any of our 4 patients at 16
      26 months after operation. DISCUSSION: The dye injection method is useful in
      determining the appropriate extent of hepatic resection for advanced gallbladder
      cancer, as it is possible to determine the necessary and sufficient amount of
      liver parenchyma that should be removed according to the perfusion area of the
      cystic veins in each individual patient.

PMID- 18333044
TI  - Operative treatment of pancreatico-bronchial fistula.
AB  - BACKGROUND: Pancreatico-bronchial fistulas are a rare complication of acute or
      chronic pancreatitis. Both conservative and surgical management have been
      described previously. CASE OUTLINE: The management of a 68-year-old woman with
      acute pancreatitis complicated by a pancreatico-bronchial fistula was reviewed.
      CT scanning and magnetic resonance cholangio-pancreatography demonstrated a
      pancreatic pseudocyst with extension into the posterior mediastinum and right
      pleura. Despite conservative management as well as ERCP with pancreatic stent
      insertion, the fistula failed to resolve. Successful management of this difficult
      problem was achieved with distal pancreatectomy and intercostal drainage.
      DISCUSSION: Pancreatico-bronchial fistulas may be managed conservatively, but
      there should be a low threshold for surgical intervention if endoscopic measures
      fail.

PMID- 18333045
TI  - Anaerobic liver abscesses as initial presentation of silent colonic cancer.
AB  - BACKGROUND: Rarely, multiple liver abscesses caused by anaerobic organisms are
      the presenting form of unsuspected colonic cancer in the absence of liver
      metastases. CASE OUTLINE: A 68-year-old man was admitted with abdominal pain,
      fever and chills. Imaging scans and repeated cytology yielded a diagnosis of
      multiple liver abscesses. Pus cultures grew Peptostreptococcus anaerobius,
      Bacteroides melaninogenicus and Peptostreptococcus spp. A search for the
      underlying cause led to the discovery of an adenocarcinoma of the sigmoid colon.
      After a 12-month postoperative follow-up, the patient is free of hepatic
      metastases. DISCUSSION: Anaerobic liver abscesses should always alert the
      clinician to possible silent colonic carcinoma.

PMID- 18333046
TI  - Supra-elevated CA 19-9 in a benign hepatic cyst adenoma.
AB  - BACKGROUND: Elevated CA 19-9 may be found in both cystadenomas and
      cystadenocarcinomas of the liver. CASE OUTLINE: A 59-year-old woman presented
      with right upper quadrant abdominal pain, malaise and weight loss. Physical
      examination and laboratory evaluation revealed a mass in the right upper quadrant
      and a CA 19-9 level of 68 661 U/ml. CT scan demonstrated a cystic liver mass. She
      underwent a right hepatectomy, and her CA 19-9 returned to normal. Pathologic
      analysis revealed no malignancy. DISCUSSION: In hepatic cystic neoplasms, an
      elevated CA 19-9 should not be used to establish the diagnosis of malignancy nor
      should it preclude resection.

PMID- 18333047
TI  - Intra-abdominal sequestration of the lung and elevated serum levels of CA 19-9: a
      diagnostic pitfall.
AB  - BACKGROUND: Extralobar pulmonary sequestration is an uncommon congenital
      abnormality that is rarely diagnosed after the age of 40 years. We describe a 64
      year-old woman with an intra-abdominal sequestration of the lung and elevated
      carbohydrate antigen (CA) 19-9 serum levels. CASE OUTLINE: On abdominal
      ultrasound a semi-solid cystic tumour was demonstrated that showed tight
      connection to the tail of the pancreas according to computed tomography.
      Cytological examination of the percutaneous biopsy did not lead to a definitive
      diagnosis. CA 19-9 serum levels were repeatedly elevated >250 IU/ml. With a
      tentative diagnosis of a tumour of the tail of pancreas the semi-solid cystic
      mass was resected. Frozen section histology suggested the diagnosis of pulmonary
      sequestration, which was confirmed by definitive histological examination.
      Immunohistochemical staining of the specimen with a specific monoclonal antibody
      against CA 19-9 showed strong immunoreactivity. Three months later the elevated
      CA 19-9 serum levels returned to normal. DISCUSSION: Elevated CA 19-9 serum
      levels have been described in benign pulmonary and mediastinal cystic lesions and
      in one case of extralobar intrathoracic lung sequestration. Although there is
      evidence that malignancies may arise in congenital lung cysts, CA 19-9 serum
      levels have not been investigated in such cases. Based on our results elevated
      serum values of CA 19-9 in combination with a cystic semi-solid mass in the left
      subphrenic space should include the differential diagnosis of extralobar
      pulmonary sequestration.

PMID- 18333048
TI  - The value of computed tomography in the diagnosis of acute necrotising
      pancreatitis in a renal transplant patient.
AB  - BACKGROUND: The incidence of acute pancreatitis after renal transplantation
      ranges around 1%, and the mortality rate is nearly 65%. Dynamic computed
      tomography (CT) scan and amylase levels are valuable in the diagnosis of this
      rare complication. CASE OUTLINE: A 29-year-old man was hospitalised with
      cytomegalovirus (CMV) pancreatitis after renal transplantation. An initial CT
      scan showed an enlarged pancreas with hypodense, heterogeneous consistency and
      with peripancreatic, perihepatic, mesenteric and pelvic fluid collections. After
      initial conservative management, follow-up CT revealed pancreatic necrosis and
      abscess formation. The patient underwent necrosectomy and repeated drainage of
      abscess facilitated by a Bogota bag, but he died 60 days after admission and five
      surgical procedures. DISCUSSION: CMV pancreatitis after renal transplantation is
      rare and frequently fatal. In the presence of an acute abdomen after renal
      transplantation, the diagnosis of pancreatitis should be considered. Dynamic CT
      scan and measurement of amylase levels are recommended.

PMID- 18333049
TI  - Hepatobiliary cystadenoma: diagnostic uncertainty.
AB  - BACKGROUND: Hepatobiliary cystadenoma is a rare tumour that can be clinically
      'silent' and only discovered as an incidental finding on ultrasonography (US). It
      can also be symptomatic with abdominal pain and jaundice or develop internal
      bleeding and (exceptionally) malignant degeneration. Therefore the treatment of
      choice is liver resection. CASE OUTLINE: A 77-year-old woman was admitted with
      mild jaundice and right hypochondrial pain. For 7 years she had been known to
      have a silent liver lesion, always considered to be a simple cyst on US. US and
      CT scan revealed a multi-septate mass involving segments IV, V and VIII of the
      liver, with thick walls, no calcifications and no contrast enhancement. US-guided
      aspiration showed the presence of old blood-stained material. The patient was
      operated with a suspected diagnosis of bleeding into a simple cyst. A Lin
      fenestration was performed with wide excision of the anterior wall of the cyst.
      Pathological examination demonstrated a mucinous hepatobiliary cystadenoma. The
      postoperative course was uneventful, and follow-up at 2 years confirmed no
      recurrence. DISCUSSION: Imaging will normally help to distinguish the occasional
      hepatobiliary cystadenoma from the common simple cyst. Otherwise, when a
      complication occurs, preoperative differentiation may become impossible, and
      requires histological examination of the cyst after surgical removal.

PMID- 18333050
TI  - Ruptured spleen: an unusual complication of laparoscopy.
AB  - INTRODUCTION: Splenic rupture is a well-known complication of open surgery but is
      much less common at laparoscopic surgery. CASE OUTLINE: A 45-year-old man
      underwent laparoscopy for perforated duodenal ulcer. The abdominal cavity was
      washed out and the ulcer was sutured. He was discharged on the fifth
      postoperative day but was readmitted because of a sharp pain in the left upper
      quadrant radiating to the left shoulder. He then developed haemorrhagic shock.
      Urgent laparotomy revealed a diffuse haemoperitoneum consequent upon a posterior
      subcapsular haematoma of the spleen. DISCUSSION: There are four previous case
      reports of splenic rupture at laparoscopy. In the present case, a posterior
      subcapsular haematoma arose during lavage of the left subdiaphragmatic area. Such
      a haematoma is undetectable during laparoscopy.

PMID- 18333052
TI  - Technical progress in liver transplantation.

PMID- 18333053
TI  - Techniques of orthotopic liver transplantation.
AB  - BACKGROUND: Throughout the history of liver transplantation many improvements
      have been made in the field of surgical technique. It is beyond the scope of this
      paper to review all aspects of surgical technique in liver transplantation; thus,
      in this review we focus on the description of our current technique in most
      cases, which is orthotopic liver transplantation with preservation of the
      inferior vena cava and temporary portocaval shunt. We advocate this technique
      because it has been demonstrated that it achieves better haemodynamic stability
      during the anhepatic phase, transfusion can be reduced and renal function is
      improved. The different options for vascular anastomoses are described,
      particularly the options for arterial anastomoses in case of finding a non
      adequate recipient hepatic artery. Technical possibilities for patients with
      preoperative portal vein thrombosis and the procedure in case of domino or
      sequential liver transplantation are further explained.

PMID- 18333054
TI  - Split liver transplantation.
AB  - BACKGROUND: Split liver transplantation offers an attractive way to increase the
      number of cadaveric grafts. In the past 10 years, it has enabled clinicians to
      minimise paediatric waiting list mortality. Two major concepts are applied in
      liver splitting. The more widely accepted approach provides a left lateral and a
      right extended liver graft to be transplanted into one child and one adult,
      respectively. To date the results from this technique are comparable to whole
      organ techniques for both the paediatric and the adult recipient. The second
      principle of splitting the liver provides two 'full' hemi-grafts-the left side
      for a small adult or big child and the right for a medium-sized adult patient.
      Full right/full left splitting is an important means of expanding the adult liver
      graft pool; however, it is a complex variant of liver transplantation that
      requires a high level of technical skill and a comprehensive knowledge of
      possible anatomic variations. Splitting for two adults should be performed in
      centres with a significant annual volume of liver transplantations, experience
      with left lateral splitting and an active program of hepatobiliary surgery. This
      brief review discusses anatomical and technical aspects and summarises the
      experience of both approaches to split liver transplantation to date.

PMID- 18333055
TI  - Auxiliary liver transplantation for acute liver failure.
AB  - BACKGROUND: In patients with acute liver failure (ALF) who fulfil criteria, liver
      transplantation is the only effective treatment which can substitute metabolic
      and excretory function of the liver. Auxiliary liver transplantation was
      developed because a significant minority of patients with ALF who fulfil
      transplant criteria can have a complete morphological and functional recovery of
      their liver. The favourable outcome reported in European series using auxiliary
      partial orthotopic liver transplantation (APOLT), the greater experience as well
      as the lessons from split liver and from living related donors have revived
      interest in this approach. In selected patients aged <40 years without
      haemodynamic instability, the use of ABO-compatible, non-steatotic grafts
      harvested from young donors with normal liver function can restore liver function
      and prevent the occurrence of irreversible brain damage. In the majority of cases
      the auxiliary graft is a right graft which is placed orthotopically after a right
      hepatectomy in the recipient. After standard immunosuppression, the recovery of
      the native liver is assessed by biopsies, hepatobiliary scintigraphy and computed
      tomography. When, on the basis of histological, scintigraphical and morphological
      data, there is evidence of sufficient regeneration of the native liver,
      immunosuppression can be discontinued progressively. Complete regeneration of the
      native liver can be observed in >50% of patients, who can be withdrawn from
      immunosuppression. Therefore the advantages of auxiliary transplantation seem to
      balance favourably with the potential inconvenience of this technique in selected
      patients.

PMID- 18333056
TI  - Living donor liver transplantation: Eastern experiences.
AB  - BACKGROUND: The techniques of living donor liver transplantation (LDLT) developed
      rapidly in the 1990s to compensate for a severe deficiency in the availability of
      liver grafts from cadaveric donors for the treatment of patients with end-stage
      liver disease. This tendency was particularly prominent in East Asia, as brain
      death donors have remained largely unavailable for a variety of reasons. Thanks
      to refinements in surgical technique and postoperative management for LDLT, the
      cumulative total of LDLTs in East Asian countries has exceeded 2000 and,
      importantly, donor mortality has yet to be encountered. Moreover, indications for
      LDLT have been successfully expanded from paediatric to adult cases, following
      the introduction of right lobe graft. The significance of LDLT under conditions
      of limited opportunities for cadaveric liver transplantation, as experienced in
      these countries, differs significantly from that seen with the numerous
      opportunities for cadaveric donors in Europe and the USA. This review describes
      not only the experiences of East Asia, but also the specific differences from
      Western countries, such as indications, graft size issues and ABO blood type
      combinations, to shed light on the future of liver transplantation.

PMID- 18333057
TI  - Technical progress in living donor liver transplantation for adults.
AB  - BACKGROUND: Liver transplantation from a living donor (LDLT) was introduced
      during the 1990 s to overcome the shortage of donor organs, particularly among
      children and in those countries in which cadaveric grafts were seldom available.
      In Japan alone, some 1700 LDLTs were performed in the first 12 years with a 5
      year survival rate of 70% in adults and an even higher rate (82%) in children.
      The major limitation to successful LDLT is inadequate graft size, which usually
      necessitates the use of the whole right liver unless (I) the caudate lobe is
      included in a left liver graft, (2) only the right lateral sector is employed
      (segments VI and VII) or (3) left livers from two donors are implanted into one
      recipient. DISCUSSION: From a technical standpoint, the main problem with the
      various types of LDLT has been the venous reconstruction in the recipient. For
      the left-sided graft, the hepatic vein of the caudate lobe should be re
      anastomosed to prevent congestion of this segment. For the right-sided graft,
      there has been uncertainty about the need to reconstruct the middle hepatic vein
      (MHV). Implantation is clearly simpler without this additional step, but there is
      a risk of dysfunction and sepsis in the right paramedian sector. Venous
      congestion in this sector can be observed during operation, both visually after
      clamping the MHV and by ultrasonographic assessment of the direction of blood
      flow in the portal vein. These techniques can be used to determine which patients
      require bench reconstruction of MHV tributaries or indeed of the inferior right
      hepatic vein. These manoeuvres should improve graft function and survival.

PMID- 18333058
TI  - Living donor liver transplantation: issues regarding left liver grafts.
AB  - BACKGROUND: The necessity of widening the indications for living donor liver
      transplantation (LDLT) has been emphasised. Clarification of the advantages and
      limitations of using a left liver graft for LDLT in adults is essential for donor
      safety. METHODS: Between June 1990 and November 2002, 185 patients underwent LDLT
      at Shinshu University Hospital, Japan. In 97 of these, the graft comprised the
      left liver with or without the left portion of the caudate lobe. The peri
      hepatectomy profiles of the donors, significance of left liver grafts,
      postoperative courses of the donors and recipients, and survival of the
      recipients were investigated. RESULTS: All the donors recovered well and returned
      to a normal lifestyle. None required banked-blood transfusion or repeat surgery,
      and postoperative liver function tests had satisfactory results. The cold
      ischaemic time for the graft was 127+/-54 minutes. The graft volumes (GVs) ranged
      from 230 to 625 ml, and GV/standard liver volume (SV) ratios varied from 22% to
      65%, at the time of transplantation. Although 85% of the liver grafts had GV/SV
      ratios <50%, no patient developed immediate postoperative liver failure. Patient
      survival rates were 89%, 84% and 84% at 1, 3 and 5 years, respectively.
      DISCUSSION: Although LDLT using a left liver graft imposes potential
      postoperative complications (a small liver is more vulnerable to injury, and
      recipients of small grafts are at higher risk of complications during recovery),
      such grafts have yielded acceptable results in adult LDLT, with minimal burden to
      the donors.

PMID- 18333059
TI  - New technique in hepatic parenchymal transection for living related liver donor
      and liver neoplasms.
AB  - BACKGROUND: Many different surgical techniques have been described for hepatic
      parenchymal transection. A retrospective analysis of perioperative mortality,
      length of hospitalization and blood transfused during operation in two patient
      groups undergoing liver resection was carried out. In group A, we developed a new
      technique to resect hepatic parenchyma, using an ultrasonic surgical aspirator
      with monopolar floating ball cautery, while in group B the crushing clamp
      technique was used. METHODS: In all, 42 patients with liver resection were
      enrolled in group A and 107 resections in group B. All patients had hepatic
      neoplasms except for seven living transplant donors. In group A 43% of resections
      involved >or=3 segments and 57% involved <or=2 segments; in group B 36.4%
      involved >or=3 segments and 63.6% consisted of <or=2 segments. Statistical
      analysis utilised independent T square (Pearson Q square) and Mann-Whitney U
      test. RESULTS: In group A 2.4% of patients died perioperatively, while 3.7% died
      in group B; mean length of stay (LOS) was 10.9 days in group B and 8.0 days in
      group A. The length of procedure was 7.5 h in group B and 6.7 h in group A. In
      group A, 79% did not undergo blood transfusion intraoperatively as opposed to 61%
      in group B. A mean of 0.5 U of blood was utilized in group A and 1.60 U in group
      B. DISCUSSION: The new method of parenchymal transection seems to reduce the LOS,
      length of procedure and need for intraoperative blood transfusion.

PMID- 18333060
TI  - Surgical treatment of multiple cystic echinococcosis.
AB  - BACKGROUND: Multiple hydatid disease is a complex surgical problem, and its
      treatment can follow either conservative principles (drainage or obliteration of
      the cavity) or radical principles (cystoperi-cystectomy or liver or lung
      resection). METHODS: A total of 220 patients with multiple cystic echinococcosis
      (428 cysts) were managed between 1967 and 1998 with conservative operations
      (group A) or radical operation (group B). There were 90 men and 130 women, with a
      mean age of 52 years (range 18-77 years). There were two cysts in 124 patients,
      three cysts in 40 patients, four in 15 and more than four in 41 patients. These
      multiple cysts were located at one anatomical site (n=140) or at more than one
      site (n=80). Multiple (2-3) hepatic cysts occurred in 142 patients, multiple (2
      3) lung cysts in 15 and multiple peritoneal cysts in 13 patients. Hepatic cysts
      co-existed with lung cysts in another 32 patients, with peritoneal cysts in 14
      patients and once each with splenic, splenic plus lung cysts and renal cysts, one
      retroperitoneal cyst coincided with small peritoneal cysts. RESULTS: The
      operative procedure employed was dependent on the type and site of the parasite
      and the condition of the host. Three of 208 patients operated conservatively
      (group A) died postoperatively as opposed to receiving radical treatment.
      Morbidity rates were 8.8% and 12.5% in group A and B and mean hospital stay was
      15.8 and 15.1 days, respectively. In group A there was an 8.6% recurrence rate,
      and recurrent disease was finally managed in each group the overall result could
      be considered satisfactory. DISCUSSION: We conclude that conservative surgery can
      provide good results in multiple cystic echinococcosis. Radical surgery, with its
      time-consuming major procedures, is ideal but only in properly selected cases.

PMID- 18333061
TI  - Hepatic resection for benign non-cystic liver lesions.
AB  - BACKGROUND: Hepatic resection is indicated for a variety of benign conditions
      because of persistent symptoms, uncertainty regarding the diagnosis or the risk
      of malignant transformation. The aim of this study was to assess the indications
      for and outcome of hepatic resection for benign non-cystic liver lesions in a
      specialist hepatobiliary unit. PATIENTS AND METHODS: All patients who had
      undergone hepatic resection for benign non-cystic hepatic lesions between 1989
      and 2001 were identified from a prospective database for analysis. RESULTS: A
      total of 49 patients (40 women, 9 men) with a mean age of 43 years (range 21-75
      years) underwent resection of non-cystic benign lesions. Indications for
      operation included suspected liver cell adenoma (n=11), suspicion of malignancy
      (11), persistent symptoms attributable to the lesion (20) or chronic sepsis (7).
      The final diagnosis was focal nodular hyperplasia (n=12), haemangioma (12),
      adenoma (8), sclerosing cholangitis (5), inflammatory pseudotumour (4),
      intrahepatic cholelithiasis (3), chronic hepatic abscess (3), benign biliary
      fibrosis (I) and leiomyoma (I). Major anatomical hepatic resections were
      performed in 44 patients, and 5 patients underwent a segmentectomy or minor
      atypical resection. Median operating time was 215 min (range 45-450 min) and
      median blood loss was 875 ml (range 200-4000 ml). Ten patients (20%) required a
      median blood transfusion of 2 units (range 2-8 units). The median postoperative
      stay was 10 days (range 4-33 days). There were no deaths, but complications
      occurred in 15 patients (27%). CONCLUSIONS: Hepatic resection can be safely
      recommended for selected patients with a variety of benign non-cystic hepatic
      lesions. A small group of patients undergo resection as a result of inability to
      rule out a malignant process, but the large majority will be operated on because
      of either their malignant potential or related symptoms.

PMID- 18333062
TI  - Curative resection by superior hepatectomy for advanced hepatoblastoma
      facilitated by the presence of a large inferior right hepatic vein.
AB  - BACKGROUND: Despite the success of neoadjuvant chemotherapy some patients with
      hepatoblastoma remain unresectable due to the proximity of important vascular
      structures. We report an unconventional surgical resection via a superior
      hepatectomy in a 16-month-old infant with hepatoblastoma. CASE OUTLINE: Staging
      CT scan revealed extensive replacement of the superior portion of the liver with
      complete occlusion of the three hepatic veins, and with extension into the
      inferior vena cava and right atrium. Following chemotherapy the tumour was
      confined to the superior portion of the liver with obstruction of the right,
      middle and left hepatic veins, but with a large patent inferior hepatic vein
      draining the inferior liver segments. Superior hepatectomy was performed without
      complication. DISCUSSION: Complete surgical resection offers the only chance of
      cure for patients with hepatoblastoma. This case illustrates that careful
      preoperative planning facilitated aggressive surgical clearance with superior
      hepatectomy for curative resection of an otherwise non-resectable tumour.

PMID- 18333063
TI  - Long-term survival with stage IV poorly differentiated pancreatic adenocarcinoma.
AB  - BACKGROUND: Metastatic poorly differentiated adenocarcinoma of the pancreas has a
      poor outcome despite the use of various chemotherapy regimes. CASE OUTLINE: A 57
      year-old woman presented with a 3-month history of generalised abdominal pain
      associated with weight loss. Computed tomography (CT) showed a large tumour in
      the head and body of pancreas, and needle biopsy confirmed a poorly
      differentiated adenocarcinoma. Laparoscopy revealed liver metastases in both
      lobes, again histologically shown to be poorly differentiated adenocarcinoma. Six
      cycles of cisplatin, epirubicin and infusional 5-fluorouracil were given. Five
      years later the patient remains completely well. Repeat CT scans show a complete
      radiological response. DISCUSSION: Previous studies using numerous chemotherapy
      regimes have not significantly altered the outcome of pancreatic cancer. To the
      best of our knowledge this is the longest surviving case of a patient with
      advanced metastatic adenocarcinoma (stage IV) of the pancreas treated with
      chemotherapy.

PMID- 18333064
TI  - Autoimmune pancreatitis in a patient presenting with obstructive jaundice and
      pancreatic mass.
AB  - BACKGROUND: Autoimmune pancreatitis (AIP) is a rare cause of chronic
      pancreatitis. CASE OUTLINE: A case of obstructive jaundice with pancreatic mass
      mimicking malignancy is described. DISCUSSION: Recognition of the disease by its
      typical radiological and serological findings permits trial of steroid therapy
      and may avoid resection.

PMID- 18333066
TI  - Selective internal radiation therapy (SIRT): a new modality for treating patients
      with colorectal liver metastases.
AB  - BACKGROUND: Selective internal radiation therapy (SIRT) is a new and developing
      modality for treating non-resectable liver tumours. Evidence is emerging that it
      is very efficacious in patients with hepatocellular cancer and colorectal liver
      metastases. DISCUSSION: SIRT generally involves a single delivery of (90)yttrium
      micro-spheres into the hepatic artery. Preferential uptake is achieved into liver
      tumours, because of their predominant hepatic arterial blood supply. Average
      tumour doses of radiation in excess of 200 Gy are achieved. The treatment is
      generally well tolerated and has been documented by a number of groups
      internationally to achieve response rates of around 90% in patients with
      extensive colorectal cancer (CRC) liver metastases. Since the product obtained
      FDA approval in the USA in 2002, it is being more widely employed and
      investigated. Unlike other ablative therapies being applied to non-resectable
      liver tumours, SIRT is indicated even in patients with an extensive burden of
      liver tumour. Indications, dosing schedules and expected outcomes will become
      better defined as more groups take up the treatment.

PMID- 18333067
TI  - Management of common bile duct stones: controversies and future perspectives.
AB  - BACKGROUND: The advent of endoscopic and minimally invasive techniques for
      diagnosis and treatment has revolutionised the management of bile duct stones.
      Yet several controversies still surround the optimal means of investigation and
      treatment. DISCUSSION: Scoring systems that classify patients according to their
      risk of harbouring bile duct stones are likely to decrease the number of
      unnecessary preoperative endoscopic cholangiopancreatograms (ERCPs) at the
      expense of a higher rate of positive intra-operative diagnosis, unless magnetic
      resonance cholangiopancreatography (MRCP) is used to supplement the clinical
      information. The current treatment that is generally preferred for patients with
      a high probability of bile duct stones is ERCP followed by laparoscopic
      cholecystectomy (LC), but the routine use of ERCP in this context has certain
      limitations. An alternative approach is offered by carrying out the necessary
      cholangiogram during LC. Laparoscopic choledochotomy requires technical skill and
      costly equipment and should usually be followed by T-tube drainage of the duct. A
      recent survey in Spain has shown that most surgeons prefer ERCP plus LC, but one
      recent randomised controlled trial showed advantages for the single-stage
      laparoscopic treatment of bile duct stones in terms of a shorter hospital stay;
      success rates and complication rates were similar for the two procedures. The
      authors support the consensus statement that the choice of diagnostic and
      therapeutic strategy should depend on local circumstances and available
      expertise.

PMID- 18333068
TI  - The role of preoperative biopsy in pancreatic cancer.
AB  - BACKGROUND: Cyto-histological diagnosis of pancreatic pathology in the management
      of suspected pancreatic malignancy is re-evaluated in the light of evolving
      trends in management and tissue sampling. METHODS: The literature on cyto
      histological diagnosis of pancreatic pathology was reviewed over the period 1977
      2003. RESULTS AND CONCLUSION: Endoluminal techniques of tissue sampling carry
      less risk of tumour seeding and are the sampling methods of choice for
      potentially resectable lesions if a tissue diagnosis will alter therapy.
      Endosonar-guided biopsy in expert hands appears to be the most reliable tissue
      sampling technique. Transcoelomic sampling methods should be reserved for those
      with un-resectable disease. All methods of cyto-histological diagnosis have high
      specificity but have a low negative predictive value. Therefore, potentially
      resectable lesions that are highly suspicious for malignancy should be explored
      even if pre-operative histology or cytology is negative.

PMID- 18333069
TI  - Binding pancreaticojejunostomy--a safe and reliable anastomosis procedure.
AB  - BACKGROUND: Over the past one hundred years, the development of
      pancreaticoduodenectomy (PD) has always involved the struggle against pancreatic
      leakage. Until now, leakage of the pancreatic anastomosis has remained a common
      and serious complication after PD. Various methods of dealing with the pancreatic
      stump for prevention of pancreatic anastomotic leakage have been described. No
      matter which method is used, however, pancreatic anastomotic leakage is still
      most likely to occur when anastomosis involves a normal and soft pancreas.
      METHODS: To perform a safe and reliable pancreaticoenteric anastomosis, we
      investigated the risk factors and potential mechanisms of occurrence of
      pancreatic leakage, including leakage from the needle hole and from the seam
      between two anastomosed structures, blood supply to the anastomosis and tension
      at the anastomosis. Based on these findings, we established a new
      pancreaticoenteric anastomosis procedure - binding pancreaticojejunostomy. The
      unique aspects of this procedure are as follows. The sero-muscular sheath of
      jejunum is bound to the invaginated pancreatic stump, so as to seal the gap
      between them; mucosa of the segment of jejunum that would eventually be in
      contact with the pancreatic stump is destroyed either chemically or by electric
      coagulation to promote healing. There is no needle hole on the jejunal surface of
      the anastomotic site. RESULTS: From 1996 to 2003, a total of 227 consecutive
      patients were treated with this type of pancreaticojejunostomy in this
      institution. None of the patients developed a pancreatic anastomotic leak.
      DISCUSSION: Binding pancreaticojejunostomy is a safe and reliable anastomotic
      procedure to effectively minimize leakage even when the texture of the pancreas
      is soft and normal.

PMID- 18333070
TI  - Necrotizing pancreatitis: a surgical approach independent of documented
      infection.
AB  - BACKGROUND: Strategies for the management of patients with necrotizing
      pancreatitis remain controversial. While consensus opinion supports operative
      necrosectomy for the treatment of infected pancreatic necrosis, the timing for
      surgical intervention is not completely resolved. Further, the indication for the
      surgical management of sterile pancreatic necrosis is also subject to debate.
      METHODS: The objective of this study was to evaluate outcome measures for the
      surgical management of necrotizing pancreatitis, independent of documented
      infection. A retrospective review was undertaken between 1994 and 2002 at a
      single county hospital. RESULTS: Twenty-one patients with CT-documented
      necrotizing pancreatitis underwent operative pancreatic necrosectomy with
      laparostomy within 21 days of initial diagnosis and had an average of three
      reoperations. Average length of stay (LOS) in the ICU was 36 days and in the
      hospital 67 days. Ten patients had documented infected necrosis based on initial
      intra-operative cultures, while I I had sterile necrosis. Overall, 95% (20/21) of
      the patients had a complication, with an average of three complications per
      patient. Common complications included ARDS (71%), sepsis (33%), renal failure
      (24%), and pneumonia (24%). The overall mortality rate was 14% (3/21), with a
      mean follow-up of 469 days. DISCUSSION: The surgical management of acute
      necrotizing pancreatitis, independent of documented infection, can be undertaken
      within 3 weeks of diagnosis with an acceptable morbidity and a low mortality
      rate. Creation of a laparostomy to enable ready, atraumatic debridement of the
      retroperitoneum is a safe alternative to standard repeat laparotomies and thus
      represents a useful adjunct to the surgical management of necrotizing
      pancreatitis.

PMID- 18333071
TI  - The protective effect of erythropoietin on ischaemia/reperfusion injury of liver.
AB  - BACKGROUND: Besides its haematopoietic effect, erythropoietin (EPO) has multiple
      protective effects, i.e. antiapoptotic, antioxidant and angiogenic properties.
      The neuroprotective effects of EPO against ischaemia have all been demonstrated
      in cell culture and animal models. The aim of the study was to evaluate the
      effect of erythropoietin on ischaemia-reperfusion injury (I/R injury) of the
      liver. METHODS: Forty-eight adult male Sprague-Dawley rats weighing 250-300 g
      were divided into three groups: group I, hepatic ischaemia-reperfusion (Hepatic
      I/R); group II, hepatic ischaemia-reperfusion + EPO (Hepatic I/R+ EPO); group
      III, sham. Hepatic ischaemia was created by placing a microvascular clamp on the
      hepatic pedicle for 45 minutes. EPO was given to group II at a dose of 1000 U/kg
      120 minutes before the onset of the ischaemia. Blood samples and liver tissues
      were obtained after 45 minutes of reperfusion from half of the rats in each
      group. The remaining rats were killed after a 24-hour observation period and
      blood and tissue samples were obtained. Blood alanine aminotransferase, tumour
      necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2) and liver tissue
      malondialdehyde (MDA) levels were determined. Liver tissue histopathology was
      also evaluated by light microscopy. RESULTS: In rats with hepatic ischaemia,
      serum levels of ALT, TNF-alpha, IL-2 and liver tissue levels of MDA were reduced
      by the administration of erythropoietin and the histopathological score was also
      less severe. CONCLUSION: This study demonstrates that pre-ischaemic
      administration of EPO has protective effects on hepatic I/R injury.

PMID- 18333072
TI  - Gallbladder carcinoma: the role of p53 protein overexpression and Ki-67 antigen
      expression as prognostic markers.
AB  - BACKGROUND: The overexpression of p53 protein and the expression of Ki-67 antigen
      may affect the survival of patients with gallbladder carcinoma. This association
      has been tested in a series of 41 patients with relatively early carcinoma of the
      gallbladder. METHODS: Forty-one surgical specimens from patients with a
      postoperative histological diagnosis of gallbladder carcinoma were studied. All
      patients were operated by simple cholecystectomy only because the tumours were
      not advanced and/or their general condition was poor. Patients submitted to
      radical operations were excluded. p53 expression was calculated from nuclear
      staining according to the intensity and extent of positive cells, as graded on a
      scale from 1 to 3; a combined score of >3 was considered as overexpression. Ki-67
      expression was calculated by the MIB-I index: the percentage of positively
      stained tumour cell nuclei out of the total tumour cells counted (n = 1000); >20%
      of stained cells was considered positive. RESULTS: Twenty-nine gallbladder
      carcinomas (71%) overexpressed p53 protein in the cell nuclei. No significant
      differences were found in relation to cell differentiation on the level of tumour
      infiltration through the gallbladder wall. Five-year survival of patients with
      gallbladder carcinoma overexpressing p53 was 17.2%, while survival of patients
      without p53 overexpression was 30% (not significant). Twenty-four cases (58.5%)
      were considered positive for the MIB-I index. There were no differences between
      the grade of cell differentiation and wall infiltration. Five-year survival of
      the patients with a MIB-I positive index was 9.2% as opposed to 27.7% for those
      with a negative index (not significant). CONCLUSIONS: p53 protein nuclear
      overexpression and Ki-67 protein expression in gallbladder carcinoma were not
      related to histological differentiation, level of gallbladder wall invasion or
      patient survival.

PMID- 18333073
TI  - Perioperative factors and outcome associated with massive blood loss during major
      liver resections.
AB  - BACKGROUND: Mortality and morbidity rates from major liver resections have
      decreased sharply over the past 25 years. This improvement is due to a better
      understanding of liver anatomy and the introduction of new operative techniques,
      but also to improved anesthetic perioperative support. Certain cases are still
      associated with voluminous blood loss. These patients may be at higher risk for
      postoperative problems and increased length of stay (LOS) in hospital. METHODS:
      We have retrospectively reviewed 115 patients undergoing major hepatic resections
      (three or more anatomic segments) with respect to operative blood loss (EBL).
      Those with an EBL >or=5000 ml (group 1; n = 39) were compared to those with an
      EBL <or=2000 ml (group 2; n=42). Type of resection, age (>or=70 years), tumor
      size, mortality, morbidity, and hospital LOS were examined. Operative reports
      were examined for any explanation for excessive blood loss. Anesthetic support
      often entailed the use of a rapid infusion system. RESULTS: The EBL was 7692+/
      3848 ml for group 1 and 1359+/-514 ml for group 2. Primary liver tumors were
      resected in 20 patients in group 1 and in 18 patients in group 2. The remaining
      resections were for metastatic tumors, primarily colorectal in origin. In group
      1, 13/39 patients had a left hepatectomy compared to 10/42 patients in group 2
      (p=0.34). The overall mortality was 5/1 15. Four deaths occurred in group 1 and
      one in group 2 (p=0.16). Two deaths in group 1 were intra-operative (hemorrhage,
      air embolism). There was no difference in the number of patients with
      complications, 12/ 39 in group 1 and 8/42 in group 2 (p=0.22). Two patients in
      group 1 required re-operation for bleeding; there were none in group 2. Largest
      tumor size did not differ between the two groups (p=0.08), nor did the proportion
      of patients aged 70 years or older (p=0.06). There was no difference in hospital
      LOS (10.54+/-6.1 vs 8.90+/-4.7 days, p=0.2l). Review of operative notes in group
      1 indicated no unusual problems in 13/39, large tumors or proximity to the
      inferior vena cava in 10/39, and bleeding from the middle hepatic vein in 7/39.
      Three patients in group 1 required total vascular exclusion for tumor removal;
      there were none in group 2. DISCUSSION: Massive EBL during major liver resection
      seems to be provoked by tumors near the inferior vena cava or major hepatic
      veins, or injury to the middle hepatic vein during operation, and not by patient
      age, tumor size alone, or type of hepatectomy. However, by avoiding prolonged
      hypotension and hypothermia with the use of rapid infusion devices, the
      perioperative course of these patients does not differ from those with much less
      EBL.

PMID- 18333074
TI  - An alternative method of wound pain control following hepatic resection: a
      preliminary study.
AB  - BACKGROUND: Epidural analgesia is considered one of the optimal methods for
      provision of postoperative pain relief in patients recovering from major upper
      abdominal operations. Concerns regarding the potential risk of neurological
      complications prompted an evaluation of an alternative strategy using a
      continuous intermuscular bupivacaine (CIB) infusion combined with patient
      controlled analgesia (PCA). METHODS: Two fine-bore catheters are inserted in the
      deep intermuscular intercostal neuronal plane during abdominal wound closure, and
      a continuous infusion of bupivacaine 0.25% is commenced for 72 h postoperatively.
      Simultaneously, patient-controlled analgesia provided intravenous morphine on
      demand. The study comprised 10 consecutive patients undergoing liver resection in
      whom CIB infusion and PCA were employed. The feasibility, safety and efficacy of
      the technique were investigated, analysing postoperative pain scores, morphine
      requirements, spirometry and oxygen saturation. RESULTS: There were no
      postoperative deaths. Postoperative morbidity included one urinary tract
      infection, one minor chest infection and acute confusional episodes in two
      patients. Median pain scores and morphine requirements at 12, 24, 48 and 72 h
      postoperatively were satisfactory. Spirometry and oxygen saturation values also
      remained within the normal range. DISCUSSION: Preliminary experience with CIB
      infusion/PCA in the aftermath of major liver resection has demonstrated its
      simplicity and safety as an alternative method of postoperative pain control.
      Further study is required to investigate the role of CIB infusion/PCA as a
      practical alternative to epidural analgesia or PCA alone.

PMID- 18333076
TI  - Guest editorial.

PMID- 18333077
TI  - Laparoscopic management of benign liver diseases: where are we?
AB  - BACKGROUND: The role of laparoscopic surgery in the management of benign cystic
      and solid liver tumours appears to differ according to each tumour type. As
      regards congenital liver cysts, laparoscopic treatment is now the gold standard
      for treating selected, huge, accessible, highly symptomatic or complicated cysts.
      In contrast, the laparoscopic approach is not useful for patients suffering from
      adult polycystic liver disease (PLD), except for type I PLD with large multiple
      hepatic cysts. For benign hepatocellular tumours, the surgical management has
      recently benefited from a better knowledge of the natural history of each type of
      tumour and from the improvement of imaging techniques in assuring a precise
      diagnosis of tumour nature. Thus the general tendency has led to a progressive
      restriction and tailoring of indications for resection in benign liver tumours,
      selecting only patients with huge, specifically symptomatic or compressive benign
      tumours or patients suffering from liver cell adenoma. Despite the enthusiastic
      use of the laparoscopic approach, selective indications for resection of benign
      liver tumours should indeed remain unchanged. For all types of benign liver
      tumours, the best indication remains small, superficial lesions, located in the
      anterior or the lateral segments of the liver. Deep, centrally located lesions or
      tumours in contact with major vascular or biliary trunks are not ideal candidates
      for laparoscopic liver resections. When performed by expert liver and
      laparoscopic surgeons using an adequate surgical technique, the laparoscopic
      approach is safe for performing minor liver resections and is accompanied by the
      usual postoperative benefits of laparoscopic surgery. When applied in selected
      patients and tumours, laparoscopic management of benign liver diseases appears to
      be a promising technique for hepatobiliary surgeons.

PMID- 18333078
TI  - Controversies in the laparoscopic treatment of hepatic hydatid disease.
AB  - BACKGROUND: Laparoscopic treatment of hydatid disease of the liver can be
      performed safely in selected patients. METHODS: Six hundred and fifty patients
      were treated for hydatid disease of the liver between 1980 and 2003 at the
      Hepatopancreatobiliary Surgery Unit of Istanbul Medical Faculty, Istanbul
      University. Of these, 60 were treated laparoscopically between 1992 and 2000. A
      special aspirator-grinder apparatus was used for the evacuation of cyst contents.
      Ninety-two percent of the cysts were at stages I, II or III according to the
      ultrasonographic classification of Gharbi. RESULTS: Conversion to open surgery
      was necessary in eight patients due to intra-abdominal adhesions or cysts in
      difficult locations. There was no disease- or procedure-related mortality. Most
      of the complications were related to cavity infections (13.5%) and external
      biliary fistulas (11.5%) resulting from communications between the cysts and the
      biliary tree. There were two recurrences in a follow-up period ranging between
      3.5 and 11 years. DISCUSSION: Laparoscopic treatment of hydatid disease of the
      liver is an alternative to open surgery in well-selected patients. Important
      steps are the evacuation of the cyst contents without spillage, sterilization of
      the cyst cavity with scolicidal agents and cavity management using classical
      surgical techniques. Our specially designed aspirator-grinder apparatus was
      safely used to evacuate the cyst contents without causing any spillage. Knowledge
      of the relationship of the cyst with the biliary tree is essential in choosing
      the appropriate patients for the laparoscopic technique. In our experience of 650
      cases, the biliary communication rate was as high as 18%; half of these can be
      detected preoperatively. In the remaining, biliary communications are usually
      detected during or after surgery. Endoscopic retrograde cholangiopancreatography
      (ERCP) and sphincterotomy are helpful to overcome this problem. As hydatid
      disease of the liver is a benign and potentially recurrent disease, we advocate
      the use of conservative techniques in both laparoscopic and open operations.

PMID- 18333079
TI  - Laparoscopic anatomic liver resection.
AB  - BACKGROUND: Liver resection is reputed to be one of the most difficult procedures
      embraced in laparoscopy. This report shows that with adequate training,
      anatomical liver resection including major hepatectomies can be performed.
      METHODS: This is a retrospective study. RESULTS: From 1995 to 2004, among 84
      laparoscopic liver resections, 46 (54%) anatomical laparoscopic hepatectomies
      were performed in our institution by laparoscopy. Nine (20%) patients had benign
      disease while 37 (80%) had malignant lesions. Among those with malignant lesions,
      14 patients had hepatocellular carcinoma (HCC), 18 had colorectal metastasis
      (CRM), while 5 had miscellaneous tumours. For benign disease, minor (two
      Couinaud's segments or less) and major anatomic hepatectomies were performed in
      five and four patients, respectively. For malignant lesions, minor and major
      anatomic hepatectomies were performed in 15 and 22 patients, respectively.
      Overall, conversion to laparotomy was necessary in 7 (15%) patients. Blood
      transfusion was required in five (10%) patients. One patient died of cerebral
      infarction 8 days after a massive peroperative haemorrhage. The overall morbidity
      rate was 34% whatever the type of resection. Three patients required reoperation,
      either for haemorrhage (n=1) and/or biliary leak (n=2). For CRM (n=18), overall
      and disease-free survival at 24 months (mean follow-up of 17 months) were 100%
      and 56%, respectively. For HCC (n=14), overall and disease-free survival at 36
      months (mean follow-up of 29 months) were 91% and 65%, respectively. No port site
      metastasis occurred in patients with malignancy. CONCLUSIONS: After a long
      training with limited liver resection in superficial segments, laparoscopic
      anatomical minor and major resections are feasible. Short-term carcinological
      results seem to be similar to those obtained with laparotomy.

PMID- 18333080
TI  - Laparoscopic resection of hepatic colorectal metastases.
AB  - BACKGROUND: Liver resection for secondary malignancy has become the standard of
      care in appropriately staged patients, offering 5-year survival rates of >40%.
      Reports of laparoscopic liver resection have been published with increasing
      frequency over the last few years. In these small series approximately one-third
      of all operations have been for malignancy, but survival figures cannot be
      assessed yet. METHODS: A retrospective review of all laparoscopic liver
      resections performed by four surgeons in Brisbane between 1997 and 2004 was done.
      Follow-up was by regular patient review and telephone confirmation. RESULTS: Of
      84 laparoscopic liver resections, 33 (39%) were for malignancy; 28 of these were
      for metastases (22 colorectal). Thirteen patients had left lateral sectionectomy
      with minimal morbidity; nine right hepatectomies were attempted and six cases of
      segmental or subsegmental resection were performed. Survival rates in 12 patients
      followed for 2 years with colorectal secondaries were 75% with 67% disease-free.
      DISCUSSION: Laparoscopic liver resection is feasible in highly selected cases of
      malignant disease. Patients need to be appropriately staged and surgeons need a
      broad experience of open liver surgery and advanced laparoscopic procedures.

PMID- 18333081
TI  - Laparoscopic liver resections for hepatocellular carcinoma (HCC) in cirrhotic
      patients.
AB  - BACKGROUND: The laparoscopic approach for liver resections is still limited and
      controversial. Nevertheless the advantages connected with a mini-invasive
      approach are significant, especially in cirrhotic patients. In recent years the
      progress of laparoscopic procedures and the development of new and dedicated
      technologies have made endoscopic hepatic surgery feasible and safe. The aim of
      this study was to report the results of our experience in laparoscopic liver
      surgery for hepatocellular carcinoma (HCC) in cirrhotic patients. METHODS: From
      2000 to 2003, 16 patients (10 male, 6 female; age 48-69 years; mean age 60.1
      years) with HCC and associated severe but well compensated liver cirrhosis
      underwent laparoscopic hepatic resections at our department. Mean tumour size was
      2.9 cm (range 1-3.9). Seven of these lesions were in the left liver and nine in
      the right lobe. Laparoscopy was performed under CO(2) pneumoperitoneum. The liver
      was always examined using laparoscopic ultrasound (US) to confirm the extension
      of the lesions and their relationships to the vasculature. The Pringle manoeuvre
      was not used. The transection of liver parenchyma was obtained by the use of a
      harmonic scalpel. The specimens were placed in a plastic bag and removed without
      contact to the abdominal wall. RESULTS: There was one conversion to laparotomy
      for inadequate exposure. In the remaining 15 patients we performed 13 non
      anatomical resections, I segmentectomy and I anatomical left lobectomy. The mean
      operative time was 152 min (range 80-180). Mean blood loss was 280 ml and none of
      the patients required blood transfusions. In two patients the resection margin
      was <1 cm but the capsule was not infiltrated at histology. One patient died on
      the third postoperative day from a severe respiratory distress syndrome. Major
      morbidities occurred in two patients who developed moderate postoperative
      ascites, which resolved successfully with conservative treatment. The mean
      postoperative hospital stay was 8.8 days. Mean follow-up time has been 18 months,
      and to date no recurrences at the site of resection or port-site metastases have
      been observed. DISCUSSION: Limited laparoscopic liver resections in cirrhotic
      patients are technically feasible with a low complication rate when careful
      selection criteria are followed (hepatic involvement limited and located in the
      left or anterior right segments, tumour size smaller than 5 cm, Child-Pugh class
      A). This approach could be considered the best option for the treatment of small
      esophitic or subcapsular HCC on well compensated cirrhosis and a useful option
      when it is necessary to perform a left lateral anatomical resection or non
      anatomical resection in well selected patients. In fact the mini-invasive
      approach can minimise the postoperative morbidity rate, which is still too high
      in this group of patients. It must be performed in highly specialised units by
      surgeons assisted by all requested technologies and with extensive experience in
      hepatobiliary and advanced laparoscopic surgery.

PMID- 18333082
TI  - Stress response to laparoscopic liver resection.
AB  - BACKGROUND: The magnitude of the systemic response is proportional to the degree
      of surgical trauma. Much has been reported in the literature comparing metabolic
      and immune responses, analgesia use, or length of hospital stay between
      laparoscopic and open procedures. In particular, metabolic and immune responses
      are represented by measuring various chemical mediators as stress responses.
      Laparoscopic procedures are associated with reduced operative trauma compared
      with open procedures, resulting in lower systemic response. As a result,
      laparoscopic procedures are now well accepted for both benign and malignant
      processes. Laparoscopic liver resection, specifically, is employed for
      symptomatic and some malignant tumors, following improvements in diagnostic
      accuracy, laparoscopic devices, and techniques. However, laparoscopic liver
      resection is still controversial in malignant disease because of complex anatomy,
      the technical difficulty of the procedure, and questionable indications. There
      are few reports describing the stress responses associated with laparoscopic
      liver resection, even though many studies reviewing stress responses have been
      performed recently in both humans and animal models comparing laparoscopic to
      conventional open surgery. Although this review examines stress response after
      laparoscopic liver resection in both an animal and human clinical model, further
      controlled randomized studies with additional investigations of immunologic
      parameters are needed to demonstrate the consequences of either minimally
      invasive surgery or open procedures on perioperative or postoperative stress
      responses for laparoscopic liver resection.

PMID- 18333083
TI  - Guest editorial.

PMID- 18333085
TI  - Diagnosis of pancreatic cancer.
AB  - The ability to diagnose pancreatic carcinoma has been rapidly improving with the
      recent advances in diagnostic techniques such as contrast-enhanced Doppler
      ultrasound (US), helical computed tomography (CT), enhanced magnetic resonance
      imaging (MRI), and endoscopic US (EUS). Each technique has advantages and
      limitations, making the selection of the proper diagnostic technique, in terms of
      purpose and characteristics, especially important. Abdominal US is the modality
      often used first to identify a cause of abdominal pain or jaundice, while the
      accuracy of conventional US for diagnosing pancreatic tumors is only 50-70%. CT
      is the most widely used imaging examination for the detection and staging of
      pancreatic carcinoma. Pancreatic adenocarcinoma is generally depicted as a
      hypoattenuating area on contrast-enhanced CT. The reported sensitivity of helical
      CT in revealing pancreatic carcinoma is high, ranging between 89% and 97%. Multi
      detector-row (MD) CT may offer an improvement in the early detection and accurate
      staging of pancreatic carcinoma. It should be taken into consideration that some
      pancreatic adenocarcinomas are depicted as isoattenuating and that pancreatitis
      accompanied by pancreatic adenocarcinoma might occasionally result in the
      overestimation of staging. T1-weighted spin-echo images with fat suppression and
      dynamic gradient-echo MR images enhanced with gadolinium have been reported to be
      superior to helical CT for detecting small lesions. However, chronic pancreatitis
      and pancreatic carcinoma are not distinguished on the basis of degree and time of
      enhancement on dynamic gadolinium-enhanced MRI. EUS is superior to spiral CT and
      MRI in the detection of small tumors, and can also localize lymph node metastases
      or vascular tumor infiltration with high sensitivity. EUS-guided fine-needle
      aspiration biopsy is a safe and highly accurate method for tissue diagnosis of
      patients with suspected pancreatic carcinoma. (18)F-fluorodeoxyglucose (FDG)
      positron emission tomography (PET) has been suggested as a promising modality for
      noninvasive differentiation between benign and malignant lesions. Previous
      studies reported the sensitivity and specificity of FDG-PET for detecting
      malignant pancreatic tumors as being 71-100% and 64-90%, respectively. FDG-PET
      does not replace, but is complementary to morphologic imaging, and therefore, in
      doubtful cases, the method must be combined with other imaging modalities.

PMID- 18333084
TI  - Genetics and pathology of pancreatic cancer.

PMID- 18333086
TI  - Preoperative biliary drainage (stenting) for treatment of obstructive jaundice.
AB  - The role of preoperative biliary drainage in malignant obstructive jaundice has
      been controversial. Laboratory studies suggest that relief of jaundice prior to
      major pancreatic resection would be associated with improved morbidity and
      mortality. However, clinical experience has not supported the laboratory results.
      Obstructive jaundice can be relieved preoperatively via an endoprosthesis
      introduced either percutaneously or endoscopically. Cohort studies have not shown
      any clinical benefit and in some the endoprostheses have been implicated in
      postoperative complications. The only randomized study has shown no benefit in
      preoperative drainage, but one recent study has confirmed that endoscopic
      drainage, whilst not conferring an advantage, did no harm. Hence, whilst
      preoperative drainage is not recommended, if for any reason operation needs to be
      delayed, endoscopic drainage via an endoprosthesis can be used without fear of
      adversely influencing the outcome.

PMID- 18333087
TI  - Pancreatic resection for pancreatic cancer.

PMID- 18333088
TI  - Adjuvant treatment.
AB  - Exocrine pancreatic cancer (pancreatic ductal adenocarcinoma) is one of the
      leading causes of cancer deaths in the western world, accounting for 5% of all
      cancer-related deaths. Only a small percentage of patients with pancreatic cancer
      are able to undergo potentially curative resection, even in specialized centres,
      and prognosis remains poor after successful surgery. Over the last few years
      efforts have been directed towards the development of adjuvant therapies in
      attempts to improve outcome. The main trials of adjuvant chemotherapy,
      chemoradiotherapy and chemoradiotherapy with follow-on chemotherapy are described
      in this paper, followed by the results of the ESPAC-1 trial and the status of
      ESPAC-2 and -3 trials.

PMID- 18333089
TI  - Resectable pancreatic cancer: the role for neoadjuvant/preoperative therapy.

PMID- 18333090
TI  - Pancreatic carcinoma: palliative surgical and endoscopic treatment.
AB  - The majority of patients with pancreatic carcinoma (hepaticojejunostomy)
      unfortunately will have palliative treatment and palliation of symptoms is
      important to improve Quality of Life. The most common symptoms that require
      palliation are jaundice, gastric outlet obstruction and pain. Obstructive
      jaundice should be treated with a biliary bypass, the optimal palliation in
      relatively fit patients and endoscopic stenting is preferred in patients with
      short survival (3-6 months). To prevent gastric outlet obstruction a prophylactic
      gastroenterostomy should be performed routinely during bypass surgery.
      Symptomatic patients after earlier stenting of the bile duct can be treated
      nowadays by duodenal stenting. Pain management is according to the progressive
      analgesic ladder but a (percutaneous) neurolytic celiac plexus block may be
      indicated. Currently a R1 (palliative) resection is acceptable in high volume
      centres but so far there is a very limited role for planned R2 palliative
      resections.

PMID- 18333091
TI  - Water-jet dissection for parenchymal division during hepatectomy.
AB  - BACKGROUND: High-pressure water-jet dissection was originally developed for
      industry where ultra-precise cutting and engraving were desirable. This
      technology has been adapted for medical applications with favorable results, but
      little is understood about its performance in hepatic resections. Blood loss may
      be limited by the thin laminar liquid-jet effect that provides precise,
      controllable, tissue-selective dissection with excellent visualization and
      minimal trauma to surrounding fibrous structures. PATIENTS AND METHODS: The
      efficacy of the Water-jet system for hepatic parenchymal dissection was examined
      in a consecutive case series of 101 hepatic resections (including 22 living donor
      transplantation resections) performed over 11 months. Perioperative outcomes,
      including blood loss, transfusion requirements, complications, and length of stay
      (LOS), were assessed. RESULTS: Three-quarters of the cases were major
      hepatectomies and 22% were cirrhotic. Malignancy was the most common indication
      (77%). Median operative time was 289 min. Median estimated blood loss (EBL) was
      900 ml for all cases, and only 14% of patients had >2000 ml EBL. Furthermore, EBL
      was 1000 ml for major resections, 775 ml for living donor resections, 600 ml in
      cirrhotic patients, and 1950 ml for steatotic livers. In all, 14% of patients
      received heterologous packed red blood cell (PRBC) transfusions for an average of
      0.59 units per case. Median LOS was 7 days. EBL, transfusion requirements, and
      LOS were slightly increased in the major resection cohort. There was one
      mortality (1%) overall. These results are equivalent to, or better than, those
      from our contemporary series of resections performed with ultrasonic dissection.
      CONCLUSION: Water-jet dissection minimizes large blood volume loss, requirements
      for transfusion, and complications. This initial experience suggests that this
      precision tool is safe and effective for hepatic division, and compares favorably
      to other established methods for hepatic parenchymal transection.

PMID- 18333092
TI  - Biliary lipids and cholesterol crystal formation in leptin-deficient obese mice.
AB  - BACKGROUND: Obesity is often associated with increased biliary cholesterol
      secretion resulting in cholesterol gallstone formation. We have previously
      demonstrated that leptin-deficient C57Bl/6J Lep ob obese mice have abnormal
      biliary motility and are prone to cholesterol crystal formation. In addition,
      others have demonstrated that leptin-deficient mice when fed a lithogenic diet
      for eight weeks are not prone to gallstone formation. However, the biliary lipid
      and in vivo cholesterol crystal response of homozygous and heterozygous leptin
      deficient mice to four weeks on a lithogenic diet has not been studied.
      Therefore, we tested the hypothesis that lithogenic diets influence gallbladder
      bile composition, serum lipids and cholesterol crystal formation in homozygous
      and heterozygous leptin-deficient mice compared to normal lean controls. METHODS:
      319 female lean control mice, 280 heterozygous lep ob obese mice and 117
      homozygous lep ob obese mice were studied. Mice were fed either a lithogenic or
      control non-lithogenic chow diet for four weeks. Gallbladder volumes were
      measured, and bile was pooled to calculate cholesterol saturation indices. Serum
      cholesterol, glucose, and leptin levels were determined. Hepatic fat vacuoles
      were counted, and bile was observed microscopically for cholesterol crystal
      formation. RESULTS: The lithogenic diet and mouse strain influenced body and
      liver weights, gallbladder volume, cholesterol crystal formation, serum
      cholesterol, glucose and leptin levels and hepatic fat vacuole numbers. However,
      only diet, not strain, altered biliary cholesterol saturation. CONCLUSION: The
      association among obesity, leptin, and gallstone formation may be primarily
      related to altered gallbladder motility and cholesterol crystal formation and
      only secondarily to biliary cholesterol saturation.

PMID- 18333093
TI  - Management of perforation after endoscopic retrograde cholangiopancreatography
      (ERCP): a population-based review.
AB  - BACKGROUND: Perforation related to endoscopic retrograde cholangiopancreatography
      (ERCP) is a rare complication associated with significant morbidity and
      mortality. This study evaluated the management and outcomes of these
      perforations. PATIENTS AND METHODS: Between July 1996 and December 2002, a total
      of 6620 ERCPs were performed at our regional endoscopy unit serving the 1.5
      million population of Southern Alberta. Thirty perforations (0.45%) were
      identified and retrospectively reviewed. Results. Seven of these 30 patients were
      found to have guidewire perforations of the bile duct, 11 perforations were peri
      ampullary, 3 duodenal, 1 esophageal, and 1 patient had a perforation of an
      afferent limb of a Billroth II anastomosis. In seven patients the location of the
      perforation could not be determined (unknown). All patients with guidewire
      perforations were recognized during ERCP, and all were managed medically. Of the
      11 peri-ampullary perforations, 7 of these patients had a pre-cut sphincterotomy,
      5 underwent surgery and 4 patients died. Delay in diagnosis occurred in all
      patients that died. Of the three duodenal perforations, all required operation
      and one patient died. Of the seven 'unknown' retroperitoneal perforations, two
      patients required surgery and there was no mortality. The patients with
      esophageal and afferent limb perforations both recovered uneventfully after
      surgery. Most patients who required surgery had retroperitoneal fluid seen on CT
      scanning. CONCLUSIONS: We found that most guidewire perforations can be managed
      medically with little morbidity. Pre-cut sphincterotomy is a risk factor for
      perforation. Peri-ampullary and duodenal perforations have a high morbidity and
      mortality rate. In particular, retroperitoneal fluid collections on CT scans,
      delay in diagnosis and failure of medical therapy requiring salvage surgery are
      associated with poor outcomes. Early aggressive surgery may improve patient care.

PMID- 18333097
TI  - The case against preoperative biliary drainage with pancreatic resection.
AB  - The majority of patients with periampullary malignancies currently undergo
      biliary drainage before pancreaticoduodenectomy. Placement of an endoprosthesis
      reliably ameliorates jaundice and pruritus. However, preoperative biliary
      drainage leads to bile colonization and increases the risk of postoperative wound
      infection after pancreatic resection. Preoperative biliary drainage does not
      appear to lower postoperative morbidity or mortality following pancreatic
      resection and does not lower but probably increases costs associated with
      pancreatic resection. Preoperative biliary drainage is frequently used with
      little clinical benefit and its utilization should be limited to specific
      clinical indications, i.e. patients receiving neoadjuvant therapy, patients
      waiting several weeks or more for surgical evaluation and resection, patients
      with cholangitis.

PMID- 18333098
TI  - Pancreatic pseudocysts--when and how to treat?
AB  - Pancreatic pseudocysts are a well-known complication of acute or chronic
      pancreatitis, with a higher incidence in the latter. Currently several
      classification systems are in use that are based on the origin of the pseudocyst,
      their relation to pancreatic duct anatomy and a possible pseudocyst-duct
      communication. Diagnosis is accomplished most often by CT scanning, by endoscopic
      retrograde cholangiopancreaticography (ERCP) or by ultrasound, and rapid progress
      in the improvement of diagnostic tools has enabled detection with high
      sensitivity and specificity. There are different therapeutic strategies:
      endoscopic transpapillary or transmural drainage, percutaneous catheter drainage,
      or open surgery. The feasibility of endoscopic drainage is highly dependent on
      the anatomy and topography of the pseudocyst, but provides high success and low
      complication rates. Percutaneous drainage is used for infected pseudocysts.
      However, its usefulness in chronic pancreatitis-associated pseudocysts is
      questionable. Internal drainage and pseudocyst resection are frequently used as
      surgical approaches with a good overall outcome, but a somewhat higher morbidity
      and mortality compared with endoscopic intervention. We therefore conclude that
      pseudocyst treatment in chronic pancreatitis can be effectively achieved by both
      endoscopic and surgical means.

PMID- 18333096
TI  - Nonoperative imaging techniques in suspected biliary tract obstruction.
AB  - Evaluation of suspected biliary tract obstruction is a common clinical problem.
      Clinical data such as history, physical examination, and laboratory tests can
      accurately identify up to 90% of patients whose jaundice is caused by
      extrahepatic obstruction. However, complete assessment of extrahepatic
      obstruction often requires the use of various imaging modalities to confirm the
      presence, level, and cause of obstruction, and to aid in treatment plan. In the
      present summary, the literature on competing technologies including endoscopic
      retrograde cholangiopancreatography (ERCP), percutaneous transhepatic
      cholangiopancreatography (PTC), endoscopic ultrasound (EUS), intraductal
      ultrasonography (IDUS), magnetic resonance cholangiopancreatography (MRCP),
      helical CT (hCT) and helical CT cholangiography (hCTC) with regards to diagnostic
      performance characteristics, technical success, safety, and cost-effectiveness is
      reviewed. Patients with obstructive jaundice secondary to choledocholithiasis or
      pancreaticobiliary malignancies are the primary focus of this review. Algorithms
      for the management of suspected obstructive jaundice are put forward based on
      current evidence. Published data suggest an increasing role for EUS and other
      noninvasive imaging techniques such as MRCP, and hCT following an initial
      transabdominal ultrasound in the assessment of patients with suspected biliary
      obstruction to select candidates for surgery or therapeutic ERCP. The management
      of patients with a suspected pancreaticobiliary condition ultimately is dependent
      on local expertise, availability, cost, and the multidisciplinary collaboration
      between radiologists, surgeons, and gastroenterologists.

PMID- 18333100
TI  - Acute pancreatitis: an under-recognized risk of percutaneous transhepatic distal
      biliary intervention.
AB  - OBJECTIVE: Percutaneous transhepatic biliary intervention (PTBI) plays an
      important role in the management of biliary obstruction, and this may be
      complicated by acute pancreatitis. The aim of this study was to assess the
      incidence of acute pancreatitis following PTBI. PATIENTS AND METHODS: Patients
      who underwent PTBI between January 1992 and December 2003 in a tertiary referral
      centre were identified from the hospital database. Patients who did not have
      their amylase measured post-procedure were excluded, as acute pancreatitis might
      have been missed. Acute pancreatitis was defined as hyperamylasaemia of three
      times or more above normal in association with abdominal pain. RESULTS: Over a 12
      year period, 331 patients underwent 613 procedures. Serum amylase was measured
      after 134 procedures (21.9%) and was elevated in 26 of those (19.4%). There was
      no difference in the frequency of hyperamylasaemia between proximal and distal
      PTBI (14/73 [19.2%] vs 12/61 [19.7%] procedures, p=NS). However, acute
      pancreatitis developed after 4 of 61 (6.6%) distal PTBI (stent, n=3; internal
      external catheter insertion, n=1) but not after proximal PTBI (cholangiography or
      external drainage) (p=0.041). The attacks were mild in three of the four
      patients. No pancreatitis-related deaths occurred. CONCLUSION: The risk of acute
      pancreatitis after distal PTBI is under-recognized and should be considered as a
      consent issue in patients scheduled for distal PTBI and when post-procedure
      abdominal pain ensues.

PMID- 18333099
TI  - Increase in serum bilirubin levels in obstructive jaundice secondary to
      pancreatic and periampullary malignancy--implications for timing of resectional
      surgery and use of biliary drainage.
AB  - BACKGROUND: Routine preoperative biliary drainage in cases of jaundice secondary
      to pancreatobiliary malignancy is associated with a significant risk of
      complications, failure and stent occlusion. It may be possible to avoid biliary
      drainage in those patients who are not deeply jaundiced. AIMS: To measure
      presenting serum bilirubin and its rate of increase in patients with malignant
      obstructive jaundice. To predict the urgency with which surgery should be
      performed to avoid preoperative biliary drainage. PATIENTS AND METHODS:
      Prospective data collection for all pancreatic and periampullary malignancies
      over a period of 18 months was carried out. Serum bilirubin levels before
      successful drainage were recorded. Rates of increase in bilirubin and the number
      of days for bilirubin to reach different thresholds were calculated. RESULTS: Of
      111 patients, 66 (59%) had resectable disease on imaging investigations. Median
      serum bilirubin on presentation was 160 micromol/l. Median increase was 13.1
      micromol/l/day or approximately 100 micromol/l/week. The predicted number of days
      for bilirubin levels to reach a variety of thresholds varied significantly. For a
      patient presenting with a serum bilirubin of 160 micromol/l, the mean number of
      days for it to rise to 200 micromol/l, 300 micromol/l, 400 micromol/l and 500
      micromol/l was 3, 13, 22 and 31 days, respectively. CONCLUSIONS: There is a
      variable window of opportunity in jaundiced patients with pancreatic and
      periampullary malignancy during which surgery may be performed to avoid biliary
      drainage procedures, depending on the threshold for operating on the jaundiced
      patient.

PMID- 18333101
TI  - Evaluation of pro-carboxypeptidase A and carboxypeptidase A as serologic markers
      for adenocarcinoma of the pancreas.
AB  - BACKGROUND: A serological marker for pancreatic cancer may allow for early
      detection and potentially more effective treatments. Pro-carboxypeptidase A (pro
      CPA) is produced exclusively in the pancreas and converted to its active form,
      CPA, in the intestinal lumen. We hypothesized that alterations in serum pro-CPA
      and/or CPA may be useful as a diagnostic test for pancreatic cancer. PATIENTS AND
      METHODS: Serum samples obtained from 34 patients with pancreatic adenocarcinoma
      prior to surgical intervention and 64 control patients were assayed for pro-CPA
      and CPA. A variety of statistical methods was used to evaluate the utility of
      these measurements individually and in combination to classify the samples with
      respect to the presence or absence of pancreatic adenocarcinoma. RESULTS: Because
      of positive skewing of the data in some populations, transformation of the data
      to natural logarithmic scales was used and resulted in normal distributions. All
      pancreatic cancer patients had ln(CPA) levels within or below the normal range
      defined as two standard deviations from the control group mean (-2.714+/-0.413).
      Ln(pro-CPA) levels in 24 of 34 cancer patients were outside the normal range of
      the control group (0.306+/-0.33). Pancreatic cancer patients with ln pro-CPA
      values within the control range had low ln CPA, advanced stage and/or evidence of
      pancreatic insufficiency. While each of these individual values (ln pro-CPA or ln
      CPA) does not adequately separate all control from cancer patients, a bivariate
      classification rule is presented that uses both ln pro-CPA and ln CPA
      simultaneously to predict the presence of pancreatic cancer with a sensitivity of
      91% and a specificity of 95%. CONCLUSIONS: The data presented suggest that
      abnormalities in serum pro-CPA and CPA levels are associated with the presence of
      pancreatic cancer.

PMID- 18333102
TI  - Iatrogenic pseudoaneurysms of the extrahepatic arterial vasculature: management
      and outcome.
AB  - BACKGROUND: Pseudoaneurysms of the extrahepatic arterial vasculature are
      relatively uncommon lesions following surgery and trauma. In this report we
      analyze the presentation, management and outcomes of these vascular lesions. Of
      the related surgical procedures, the reported incidence is highest following
      laparoscopic cholecystectomy. We hereby analyze the literature on this subject
      and report our experience, specifically with extrahepatic pseudoaneurysms,
      drawing an important distinction from intrahepatic pseudoaneurysms. METHODS: From
      September 1995 until July 2004, six patients, including three males and three
      females with a mean age of 67 years, were treated for seven extrahepatic arterial
      pseudoaneurysms. Patients were evaluated by endoscopy, ultrasound, computerized
      tomography, and angiography. Management included coil embolization or arterial
      ligation and/or hepatic resection. RESULTS: The mean pseudoaneurysm size was 4.9
      cm (range 1.0-11.0-cm) and the locations included the right hepatic artery (n =
      5), inferior pancreaticoduodenal artery (n = 1), and gastroduodenal artery (n =
      1). All six patients had prior surgical or percutaneous procedures. Median
      latency period between the original procedure and treatment of pseudoaneurysm was
      17 weeks (range one month-16 years). Clinical features ranged from the dramatic
      presentation of hypotension secondary to intraperitoneal aneurysmal rupture to
      the subtle presentation of obstructive jaundice secondary to pseudoaneurysm mass
      effect. The range of patient presentations created diagnostic challenges, proving
      that accurate diagnosis is made only by early consideration of pseudoaneurysm.
      Management was ligation of the right hepatic artery (n = 4) and embolization of
      the pseudoaneurysms (n = 2). Post-treatment sequelae included liver failure
      requiring liver transplant (n = 1), intrahepatic biloma requiring percutaneous
      drainage (n = 1) and cholangitis with right hepatic duct strictures requiring
      right lobectomy and biliary reconstruction (n = 1). These complications followed
      arterial ligation, with no complications resulting from embolization. All six
      patients are alive and well after a mean follow-up of 53 months. CONCLUSIONS: Our
      six patients demonstrate the diversity and unpredictability with which a
      pseudoaneurysm of the extrahepatic arterial vasculature may present in terms of
      initial symptoms, prior procedures, and the latency period between presentation
      and prior procedure. Through our experience and an analysis of the literature, we
      recommend a diagnostic and management approach for these patients.

PMID- 18333103
TI  - Results of vascular resections during pancreatectomy from two European centres:
      an analysis of survival and disease-free survival explicative factors.
AB  - OBJECTIVES: The object of our study was to report on the experience with vascular
      resections at pancreatectomy in two European specialist hepatopancreatobiliary
      centres and evaluate outcome and prognostic factors. PATIENTS AND METHODS: From
      1989 to 2002, 45 patients (21 men, 24 women) underwent pancreatectomy for a
      pancreatic mass: Whipple's procedure (n=33), total pancreatectomy (n=10) or left
      splenopancreatectomy (n=2), along with a vascular resection, i.e. venous (n=39),
      arterial (n=1) or venous + arterial (n=5). RESULTS: Operative mortality was nil,
      postoperative mortality was 2.2% (n=1); 34 patients had an uneventful
      postoperative course. Reoperations were performed for portal vein thrombosis
      (n=1), pancreatic leak (n=1), gastric outlet syndrome (n=1) and gastrointestinal
      bleeding (n=1). In all, 43 patients had cancer on pathology examination, with
      retropancreatic invasion in 72% and lymph node extension in 62.8%. Resection was
      R0 in 21 cases. Vessel wall invasion was present in 13 cases and 19 had
      perivascular invasion. Disease-free survival (DFS) at 1, 2 and 3 years was 36.0%,
      15.0% and 12.0%, respectively. Median DFS length was 8.7 months (95% CI: 7.2;
      10.2). Overall survival rates were 56.6%, 28.9% and 19.2%, respectively. Median
      survival length was 14.2 months (95% CI: 9.8; 18.6). A multivariate analysis of
      prognostic variables identified tumour location (other than head of pancreas),
      neoadjuvant chemotherapy and advanced disease stage as adverse factors for DFS.
      CONCLUSION: Survival and DFS rates of these patients are comparable to those
      without vascular resection. Tumour localization, tumour stage, neoadjuvant
      treatment and tumour recurrence are explanatory variables of survival. Tumour
      localization, tumour stage and neoadjuvant treatment were explanatory variables
      for DFS. However, the type and extent of vascular resections as well as vessel
      wall invasion does not affect survival and DFS.

PMID- 18333105
TI  - Research in HPB.

PMID- 18333104
TI  - Mirizzi's syndrome--results from a large western experience.
AB  - BACKGROUND: This paper reports a series of patients with Mirizzi's syndrome (MS)
      who were managed at our institution over an 11-year (1994-2005) period. METHODS:
      Retrospective case note study of patients with a definitive or possible diagnosis
      of MS stated in radiology reports were identified using the hospital's radiology
      computer coding system. RESULTS: 33 patients were identified with a median age of
      diagnosis of 70 (35-90) years and male to female ratio of 15:18. Liver function
      tests were deranged in all patients. Pre-operative radiological diagnosis was
      achieved in 28 patients: ultrasound scan (n = 4), computer tomography (n = 3),
      magnetic resonance cholangiopancreatography (n = 10) and endoscopic retrograde
      cholangiopancreatography (n = 11). Five patients were diagnosed intra
      operatively. Type I MS was reported in 27 patients. Laparoscopic cholecystectomy
      was attempted in 18 patients with 6 being converted to open cholecystectomy. Six
      patients had biliary stent insertion only and 3 were conservatively managed. Six
      patients had type II MS, 4 were treated with open cholecystectomy and Roux-en-Y
      hepaticojejunostomy, 1 underwent an open subtotal cholecystectomy with fistula
      closure and 1 had percutaneous biliary stent insertion only. The median follow-up
      period was 2 (1-7) months (n = 18). 10 patients are currently under follow-up.
      Overall morbidity was 27% (n = 8) and mortality was 7% (n = 2). CONCLUSION: Pre
      operative diagnosis of MS can be achieved using MRCP. Laparoscopic
      cholecystectomy for type I MS is a safe option and type II MS can be treated with
      Roux-en-Y hepaticojejunostomy or subtotal cholecystectomy with fistula closure.

PMID- 18333106
TI  - An update on familial pancreatic cancer and the management of asymptomatic
      relatives.
AB  - Families of patients with pancreatic adenocarcinoma (PC) often ask about their
      own risk of developing this disease. There is now a sufficient body of evidence
      to inform relatives of their relative risk of developing PC. The purpose of this
      review is to provide practical advice for the clinician when confronted with
      questions about the risk of PC in relatives, and the role of genetic testing and
      screening in high-risk individuals.

PMID- 18333107
TI  - Anastomotic leakage in pancreatic surgery.

PMID- 18333109
TI  - Hemoglobin A1c can be helpful in predicting progression to diabetes after Whipple
      procedure.
AB  - INTRODUCTION: Normoglycemic patients undergoing pancreaticoduodenectomy (Whipple
      procedure) often inquire whether they will be diabetic postoperatively. There is
      limited information on this issue. We therefore looked at a more subtle
      measurement of long-term glycemic control, hemoglobin A1c (HgbA1c), as a
      prognostic tool in predicting progression to diabetes post Whipple. PATIENTS AND
      METHODS: A retrospective review over a 6-year period of all patients undergoing
      Whipple procedures at a single institution was conducted. In all, 27 patients had
      no prior history of diabetes, complete follow-up, and measured preoperative
      HgbA1c values. Postoperative diabetes was defined as the need for oral
      hypoglycemic agents or insulin. These charts were analyzed for progression to
      diabetes after Whipple. RESULTS: Of the 27 patients, 10 were considered to have
      postoperative diabetes. The average preoperative HgbA1c value for these patients
      was 6.3+/-0.66. This was statistically different from the 17 patients without
      postoperative diabetes (average HgbA1c 5.2+/-0.39, p<0.001). The positive
      predictive value, negative predictive value, sensitivity, and specificity were
      82%, 94%, 90%, and 88%, respectively. CONCLUSION: This study demonstrates that
      progression to diabetes is very unlikely after Whipple operation if the
      preoperative HgbA1c value is in the normal range. The apparent utility of HgbA1c
      in predicting postoperative diabetes in this small study suggests that this
      laboratory test may be very helpful in counseling patients for Whipple operation.

PMID- 18333108
TI  - Adenoviral p53 gene transfer and gemcitabine in three patients with liver
      metastases due to advanced pancreatic carcinoma.
AB  - BACKGROUND: Current therapies for adenocarcinoma of the pancreas do not improve
      the life expectancy of patients. METHODS: In a non-randomized pilot trail we
      tested whether a local therapy based upon an adenoviral gene transfer of wild
      type p53 in combination with gemcitabine administration would be safe in patients
      with liver metastases due to pancreatic carcinoma. We report on the clinical
      course of three patients with respect to safety, tolerability and tumor response.
      RESULTS: Transient grade III toxicities occurred with fever, leucopenia,
      elevation of AP, ALT, AST, GGT, while grade IV toxicity occurred for bilirubin
      only. Laboratory tests suggested disseminated intravascular coagulation in all
      three patients, but fine needle biopsies of liver did not show any histological
      evidence of thrombus or clot formation. Progression of liver metastases was
      documented in one and stable disease in another patient two months after
      treatment. However, a major improvement with regression of the indexed lesion by
      80% occurred in a third patient after a single administration of 7.5 x 10(12)
      viral particles, and time to progression was extended to six months. CONCLUSION:
      The combination therapy of viral gene transfer and chemotherapy temporarily
      controls and diminishes tumor burden. Improvement of the toxicity profile is
      necessary. Further trials are warranted to improve treatment and life expectancy
      of patients suffering from fatal diseases such as pancreatic carcinoma.

PMID- 18333110
TI  - Two hundred and forty-one consecutive liver resections: an experience from India.
AB  - BACKGROUND: Although liver resection has become an established procedure in
      western countries and South-east Asia it is still not performed frequently in
      most centres in India. In the last 10 years newly created specialized units have
      been performing more liver resections but no major series have been reported.
      PATIENTS AND METHODS: We analysed the results of 241 hepatic resections in the
      Gyan Burman Liver Unit, Sir Ganga Ram Hospital to compare our results with those
      published from established centres and to identify the factors relating to
      morbidity and mortality. To examine the effect of a greater experience with the
      procedure we compared the outcome of our operations from 1996-2000 (first period)
      and those from 2001-2005 (second period). RESULTS: The overall mortality and
      morbidity rates were 6.6% and 44.8%, respectively, which are comparable with
      those of most recently published Western series. Life-threatening complications
      occurred in 12.4% patients. Multivariate analysis showed that the presence of
      comorbid conditions, intraoperative blood transfusions of >3 units,
      hepatocellular carcinoma with underlying cirrhosis and gall bladder carcinoma
      with jaundice were the independent risk factors for morbidity, whereas the
      presence of comorbid illness and underlying liver cirrhosis were the risk factors
      for mortality. During the second period there was an increase in the number of
      operations performed (66 vs 175; first vs second period), but the mortality rates
      remained essentially unchanged (6.1% vs 6.8%). DISCUSSION: Hepatic resections can
      be performed safely in India with results comparable to those achieved in the
      West. Increasing experience did not reduce overall mortality. Perhaps more
      careful patient selection and better perioperative management of comorbid
      illnesses may reduce the morbidity and mortality further.

PMID- 18333111
TI  - An experimental study of the treatment of liver injury with InLine RFA.
AB  - BACKGROUND: The liver is the most frequently injured abdominal organ after blunt
      injury; sometimes it may be very difficult to achieve haemostasis. In this study
      we examined the use of InLine radiofrequency ablation (RFA) for the coagulation
      and haemostasis of simulated liver injury. MATERIALS AND METHODS: Six pigs were
      tested in this study. We created two types of grade III to IV liver injury:
      peripheral and central. Then treatment with InLine RFA was compared to
      conventional diathermy and suture. A total of 32 surgeries were performed:
      peripheral injury (12 InLine versus 6 diathermy + suture); central injury (8
      InLine versus 6 diathermy + suture). RESULTS: The reduction of blood loss was
      63.88% in peripheral injury and 53.57% in central injury, respectively. There
      were significant differences in both types of injuries as regards blood loss
      (p<0.05) and blood loss per cm(2) (p<0.05). CONCLUSIONS: InLine RFA is
      efficacious in treating liver injuries in pigs and may have a significant
      potential for some human liver injuries.

PMID- 18333112
TI  - A cost-utility analysis of treatments for malignant liver tumours: a pilot
      project.
AB  - BACKGROUND: Hepatic resection is the standard treatment for colorectal liver
      metastases when feasible. Techniques such as radiofrequency ablation (RFA) have
      been the subject of ongoing research in hopes of achieving a similar survival to
      that achieved with hepatic resection, but with less morbidity and better quality
      of life (QOL). The aim was to to generate a hypothesis concerning the cost
      utility of various treatments that may be further tested with randomized trials
      in the future. PATIENTS AND METHODS: This was a prospective, non-randomized pilot
      study comparing the cost-utility of hepatic resection, RFA, systemic
      chemotherapy, and symptom control alone for colorectal liver metastases. All
      patients with newly diagnosed liver malignancies were eligible. QOL was measured
      serially with the Health Utilities Index. Costs, in 2001 Canadian dollars, were
      captured from the viewpoint of society in general. RESULTS: In all, 40 patients
      were enrolled in the study: 7 underwent hepatic resection, 7 underwent RFA
      (sometimes in combination with resection), 20 received systemic chemotherapy, and
      6 received symptom control alone. Liver resection appeared to be the most
      effective approach, with an average benefit of 2.58 QALYs (quality-adjusted life
      years) compared with 1.95 QALYs for RFA, 1.18 QALYs for chemotherapy, and 0.82
      QALYs for symptom control alone, resulting in cost-utility ratios of $7792,
      $8056, $12,571, and $4788 per QALY, respectively. DISCUSSION: The cost-utility of
      hepatic resection and RFA appeared similar even though patients receiving RFA had
      more advanced disease. The role of RFA is still being defined; however, if long
      term survival proves to be promising, then this study lends support to the
      conduct of randomized controlled trials in the future.

PMID- 18333113
TI  - Evaluation of cell salvage autotransfusion utility during liver transplantation.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) may be associated with massive
      blood loss and the need for allogenic blood product transfusions. Cell salvage
      autotransfusion (CS) is an attractive alternative to allogenic red blood cell
      (RBC) transfusion. However, controversy surrounds its usefulness during OLT; some
      studies stated that CS decreased transfusions of allogenic blood products and
      others stated that blood loss was increased. The aim of this study was to
      evaluate the efficiency of the CS during OLT. PATIENTS AND METHODS: After
      approval by the institutional ethics committee, a prospective survey was
      undertaken. A total of 150 consecutive OLTs were included in the study. Two
      groups of patients were formed. Period 1 included patients 1-75 with no CS use.
      Period 2 comprised patients 76-150 with systematic CS use. RESULTS: Patients from
      both periods were comparable. CS was used in all cases in period 2, and there was
      enough salvaged blood to retransfuse 65% of these OLTs. The mean volume of
      retransfused blood was 338+/-339 ml. The transfusion rate did not change from
      period 1 to period 2. The mean number of RBC units transfused per patient was
      0.4+/-0.9 vs 0.4+/-1.2 with 78.7% vs 81.3% of cases not receiving transfusion of
      any blood product. The threshold for RBC transfusions was the same. The length of
      surgery and blood loss were greater in period 2 than in period 1 (associated with
      the arrival of two junior surgeons), but the hemoglobin (Hb) value was also
      higher at the end of surgery (93.8+/-19.3 g/L vs 85.2+/-17.8 g/L, p<0.0001).
      CONCLUSION: Despite increased blood loss in period 2, CS saved 21 g/L of Hb per
      patient or two RBC unit transfusions. As long as we cannot predict with accuracy
      which patients will bleed, we will continue to use the CS for all OLTs.

PMID- 18333114
TI  - Laparoscopic staging in selected patients with colorectal liver metastases as a
      prelude to liver resection.
AB  - BACKGROUND: Careful selection of patients with colorectal liver metastases for
      liver resection should minimize the risk of unnecessary laparotomy due to
      unresectable disease. The impact of staging laparoscopy with laparoscopic
      ultrasonography (LapUS) on clinical decision making in selected patients with
      potentially resectable colorectal liver metastases was evaluated. PATIENTS AND
      METHODS: Staging laparoscopy with or without LapUS was performed in 77 of 415
      consecutive patients (19%) with colorectal liver metastases deemed potentially
      resectable following liver-specific CT and/or MRI scanning. Retrospective
      analysis of prospectively collected data compared clinical outcomes with those in
      whom laparoscopy had been deferred in favour of laparotomy. RESULTS: Staging
      laparoscopy was successful in 76 of 77 patients (99%). Adverse events occurred in
      three patients (4%): bowel injury n=2; late port site metastasis, n=1.
      Laparoscopic staging identified factors precluding curative resection in 16
      patients (21%), thus averting unnecessary laparotomy. Of the 57 patients (74%)
      staged laparoscopically who underwent surgical exploration, 7 patients (12%) were
      unresectable and liver resection was achieved in 50 (88%). DISCUSSION:
      Laparoscopic staging remains useful in detecting occult intra- and extra-hepatic
      tumour in selected patients with potentially operable colorectal liver
      metastases.

PMID- 18333115
TI  - Aggressive surgical resection for the management of hepatic metastases from
      gastrointestinal stromal tumours: a single centre experience.
AB  - BACKGROUND: The outcome of surgical intervention for hepatic metastases from
      gastrointestinal stromal tumours (GIST) is still uncertain. This study evaluated
      the outcome of patients following aggressive surgical resection and Imatinib
      mesylate therapy (IM). PATIENTS AND METHODS: This was a retrospective analysis of
      patients managed with hepatic metastases from GIST over a 13-year period (January
      1993 to December 2005). RESULTS: Twelve patients were identified with a median
      age at diagnosis of 62 (32-78) years. The primary sites of GIST were stomach
      (n=5), jejunum (n=4), sigmoid (n=1), peritoneum (n=1) and pancreas (n=1). Eleven
      patients underwent surgical resection with curative intent and one patient had
      cytoreductive surgery. Following surgery with curative intent (n=11), the overall
      2- and 5-year survival rates were both 91%, whereas the 2- and 5-year disease
      free rates following primary hepatic resection were 30% and 10%, respectively.
      The median disease-free period was 17 (3-72) months. Eight patients had recurrent
      disease and were managed with further surgery (n=3), radiofrequency ablation
      (RFA) (n=2) and IM (n=8). Overall, there are four patients who are currently
      disease-free: two patients following initial hepatic resection and two patients
      following further treatment for recurrent disease. There was no significant
      association in clinicopathological characteristics between patients with
      recurrent disease within 2 years and patients who were disease-free for 2 years
      or more. Overall morbidity was 50% (n=6), with one postoperative death. The
      follow-up period was 43 (3-72) months. CONCLUSION: Surgical resection for hepatic
      GIST metastases may improve survival in selected patients. Recurrent disease can
      be managed with surgery, RFA and IM.

PMID- 18333116
TI  - Skeletal metastasis in gall bladder cancer.
AB  - This report describes an interesting and unusual case of carcinoma gallbladder
      with skull metastasis.

PMID- 18333117
TI  - A symptomatic second gallbladder 7 years post initial cholecystectomy.

PMID- 18333119
TI  - Recent advances and controversies in surgical management of liver diseases:
      summary of liver sessions of 7th World Congress of IHPBA 2006.

PMID- 18333120
TI  - Advances in biliary tract surgery--summary of IHPBA Edinburgh 2006.

PMID- 18333121
TI  - New insights in surgical pancreatology.

PMID- 18333122
TI  - Hepato-pancreato-biliary fat: the good, the bad and the ugly.
AB  - Obesity has become epidemic in the United States, in Europe, and in many urban
      areas in the developing world. The globalization of certain 'fast foods' and
      'soft drinks' may, in part, be contributing to this epidemic. Diets high in
      saturated fatty acids and trans fats as well as drinks that have high fructose
      corn syrup levels may be particularly harmful. Recent research suggests that fat
      is a dynamic endocrine organ and that visceral fat is associated with the
      metabolic syndrome. Central obesity leads to organ steatosis and altered serum
      adipokines including reduced adiponectin and markedly elevated leptin. This
      abnormal adipokine milieu results in increased tissue infiltration of monocytes
      and macrophages which produce proinflammatory cytokines that alter organ
      function. Over many years, the combination of steatosis and local inflammation
      leads to fibrosis and eventually to cancer. Nonalcoholic fatty liver disease
      (NAFLD) is a precursor for nonalcoholic steatohepatitis (NASH). NAFLD and NASH
      (1) lead to cirrhosis and hepatocellular carcinoma, (2) increase the risk of
      liver resection, and (3) compromise the outcome of liver transplantation.
      Similarly, in the pancreas nonalcoholic fatty pancreas disease (NAFPD) may lead
      to nonalcoholic steatopancreatitis (NASP). NAFPD and NASP may (1) promote the
      development of chronic pancreatitis and pancreatic cancer, (2) exacerbate the
      severity of acute pancreatitis, and (3) increase the risk of pancreatic surgery.
      In the gallbladder nonalcoholic fatty gallbladder disease (NAFGBD,
      cholecystosteatosis) may lead to steatocholecystitis. Cholecystosteatosis may be
      an explanation for (1) the increased incidence of chronic acalculous
      cholecystitis and (2) the increased number of cholecystectomies.

PMID- 18333123
TI  - Liver transplantation for non-hepatocellular carcinoma malignancy.
AB  - Liver transplantation (LT) for hepatocellular carcinoma is effective for selected
      patients. LT for other malignancies like cholangiocarcinoma (CCA), hepatoblastoma
      (HB), hepatic epithelioid hemangioepithelioma (HEHE), angiosarcoma (AS), and
      neuroendocrine tumors (NET) is being defined. For CCA, series that did not
      emphasize highly selected early stage disease and neoadjuvant or adjuvant
      chemoradiation had an average 5-year survival of 10%. However, emphasizing
      neoadjuvant radiation and chemosensitization in operatively confirmed stage I or
      II hilar CCA has led to improved 5-year survival, up to 82%. LT is indicated
      under strict research protocols at selected centers, for patients with early
      stage CCA and anatomically unresectable (Bismuth type IV) lesions. HB is
      typically sensitive to cisplatin-based chemotherapy. LT plays a role as primary
      surgical therapy for those individuals in whom tumors remain unresectable after
      chemotherapy or as rescue therapy for those who are incompletely resected, recur
      after resection, or develop hepatic insufficiency after chemotherapy and/or
      resection. Long-term survival is reported at 58-88%. HEHE is a multifocal tumor
      that lies somewhere between benign hemangiomas and malignant AS. The extensive
      multifocal nature makes resection difficult and LT an attractive option. Series
      on LT for HEHE report overall survival of 71-78% at 5 years. However, AS is an
      aggressive tumor and LT is contraindicated. For NET, resection of the primary
      tumor and all gross metastatic disease is reported to provide 5-year survival of
      70-85%. LT has been employed for some patients for unresectable tumors or for
      palliation of medically uncontrollable symptoms with 5-year survival reported
      between 36% and 80%.

PMID- 18333124
TI  - New advances in the management of biliary tract cancer.
AB  - Biliary tract cancers are uncommon malignancies arising from biliary epithelium
      intrahepatically (peripheral cholangiocarcinoma), in the extrahepatic bile duct,
      the gall bladder and the ampulla of Vater. Treatment has been challenging because
      of late presentation, complex surgery, complex biliary obstruction with jaundice
      and a paucity of high quality data on which to establish standard care. With
      improvements in imaging, biliary stenting, surgical management and the
      establishment of a national investigational programme we hope to define the
      modern management of biliary tract cancers and enable a platform for further
      research.

PMID- 18333125
TI  - Pentoxifylline inhibits liver expression of tumor necrosis factor alpha mRNA
      following normothermic ischemia-reperfusion.
AB  - BACKGROUND: Pentoxifylline (PTX) has been shown to reduce hepatic injury after
      normothermic ischemia and reperfusion (I-R) in rat liver. AIM: The aim of this
      study was to evaluate the effects of PTX on liver expression of tumor necrosis
      factor alpha (TNFalpha) mRNA following normothermic liver I-R. MATERIALS AND
      METHODS: A segmental normothermic ischemia of the liver was induced in male Lewis
      rats by occluding the blood vessels including the bile duct to the median and
      left lateral lobes for 90 min. At the end of ischemia the nonischemic liver lobes
      were resected. Rats were divided into three groups: group 1, control Ringer
      lactate administration; group 2, PTX treatment; group 3, sham-operated control
      rats. PTX (50 mg/kg) was injected intravenously 30 min before and 60 min after
      induction of ischemia. Survival rates were compared and the serum activities of
      TNFalpha, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT),
      and lactate dehydrogenase (LDH) were measured. Histology of the liver was
      assessed 6 h after reperfusion. Liver TNFalpha mRNA was assessed by PCR
      amplification at 0, 60, 120, and 210 min after reperfusion. RESULTS: PTX
      treatment significantly increased 7 day survival (93.3%) compared with nontreated
      control rats (46.6%, p<0.007). The extent of liver necrosis and the release of
      liver enzymes were significantly decreased after PTX treatment. Serum activities
      of TNFalpha were significantly decreased and liver expression of TNFalpha mRNA
      was inhibited after PTX treatment. CONCLUSION: PTX protects the liver from
      ischemic injury and inhibits liver expression of TNFalpha mRNA.

PMID- 18333126
TI  - Hepatic tumor ablation with clustered microwave antennae: the US Phase II trial.
AB  - BACKGROUND: Thermal ablation techniques have become important treatment options
      for patients with unresectable hepatic malignancies. Microwave ablation (MWA) is
      a new thermal ablative technique that uses electromagnetic energy to produce
      coagulation necrosis. We report outcomes from the first clinical trial in the
      United States using MWA and a 915 MHz generator. PATIENTS AND METHODS: Patients
      with unresectable primary or metastatic liver cancer were enrolled in a multi
      institutional trial from March 2004 through May 2006. Demographic information,
      diagnosis, treatment, and outcomes were documented. RESULTS: Eighty-seven
      patients underwent 94 ablation procedures for 224 hepatic tumors. Forty-two
      ablations (45%) were performed open, 7 (7%) laparoscopically, and 45 (48%)
      percutaneously. The average tumor size was 3.6 cm (range 0.5-9.0 cm). Single
      antenna ablation volumes were 10.0 ml (range 7.8-14.0 ml), and clustered antennae
      ablation volumes were 50.5 ml (range 21.1-146.5 ml). Outcome variables were
      measured with a mean follow-up of 19 months. Local recurrence at the ablation
      site occurred in 6 (2.7%) tumors, and regional recurrence occurred in 37 (43%)
      patients. With a mean follow-up of 19 months, 41 (47%) patients were alive with
      no evidence of disease. There were no procedure-related deaths. The overall
      mortality rate was 2.3%. CONCLUSIONS: Microwave ablation is a safe and effective
      technology for hepatic tumor ablation. In our study, clustered antennae resulted
      in larger ablation volumes. Further studies with histological confirmation are
      needed to verify clinical results.

PMID- 18333127
TI  - Selective MRCP in the management of suspected common bile duct stones.
AB  - BACKGROUND: It is controversial whether selective endoscopic sphincterotomy or
      routine laparoscopic bile duct exploration is the optimal treatment for
      choledocholithiasis. Magnetic resonance cholangio-pancreatography (MRCP) is a
      safe and accurate imaging modality; this study evaluated its use in a clinical
      algorithm for the management of suspected choledocholithiasis. PATIENTS AND
      METHODS: Consecutive patients presenting with suspected common bile duct (CBD)
      stones were managed according to an algorithm involving the selective use of MRCP
      to identify patients who required endoscopic sphincterotomy and bile duct
      clearance. Following radiological demonstration of a clear CBD, all patients were
      considered for cholecystectomy. RESULTS: From 157 consecutive patients, 68
      proceeded straight to endoscopic sphincterotomy, which was therapeutic in 59. Of
      89 who underwent MRCP, choledocholithiasis was demonstrated in 29; subsequent
      endoscopic sphincterotomy was therapeutic in 22. MRCP demonstrated a clear CBD in
      the remaining 60 patients. Seventy-four patients subsequently underwent
      cholecystectomy, with a conversion rate of 9% and a median postoperative stay of
      1 day. There were no instances of post-sphincterotomy pancreatitis or haemorrhage
      requiring transfusion. CONCLUSION: An algorithm involving selective MRCP with
      endoscopic sphincterotomy is a safe, effective means of managing suspected
      choledocholithiasis, particularly where the expertise, equipment or theatre time
      for laparoscopic bile duct exploration is not routinely available.

PMID- 18333128
TI  - Acute acalculous cholecystitis: challenging the myths.
AB  - BACKGROUND: Acute acalculous cholecystitis (AAC) is traditionally known to occur
      in critically ill patients, following cardiac surgery, abdominal vascular
      surgery, severe trauma, burns, prolonged fasting, total parenteral nutrition, or
      sepsis, and is believed to have a worse prognosis as compared with acute
      cholecystitis associated with stones. Our observation of de novo presentation of
      AAC in several outpatients in the absence of critical illness or predisposing
      factors prompted us to undertake this study. The aims of the present study were
      to examine the prevalence of AAC patients in the outpatient setting in our
      hospital, to identify associated risk factors and to assess the clinical course
      and outcome of these patients. PATIENTS AND METHODS: All patients who had a
      cholecystectomy (laparoscopic or open surgery) for acute cholecystitis at
      National University Hospital from January 2001 to May 2005 were reviewed from a
      prospectively maintained database. The demographic characteristics,
      clinicopathologic features, operative parameters, postoperative course, and
      histopathology of the patients were reviewed. RESULTS: Eleven of 133 patients
      with acute cholecystitis fulfilled the criteria for the diagnosis of AAC.
      Patients' ages ranged from 30 to 69 years (mean 52.39 years). All these patients
      presented as outpatients. None of the patients had any critical illness
      predisposing to AAC. The mean age was slightly less in the AAC group as compared
      with the remaining patients with acute cholecystitis (52.39 years vs 55.22 years,
      p=0.54). There was male predominance in the AAC group (male:female = 9:2). The
      time from admission to surgery, operative procedure, operative time, and
      postoperative stay were not statistically different from the remaining patients
      with acute cholecystitis. DISCUSSION: AAC can occur in young and middle-aged
      healthy individuals, the presentation is no different from acute calculous
      cholecystitis, the prognosis is good if diagnosed and treated early.

PMID- 18333129
TI  - Frequency and prognostic significance of occult tumor cells in lymph nodes in
      patients with adenocarcinoma of the papilla of Vater.
AB  - BACKGROUND: Occurrence of tumor relapse is frequent in patients with carcinoma of
      the papilla of Vater despite the absence of residual tumor detectable at primary
      surgery. Therefore it has to be assumed that current tumor staging procedures
      fail to identify minimal amounts of tumor cells disseminated to secondary organs,
      which might be precursors of subsequent metastatic relapse. The aim of the study
      was to assess the frequency and prognostic impact of minimal tumor cell spread in
      lymph nodes classified as 'tumor-free' in routine histopathologic evaluation.
      MATERIALS AND METHODS: A total of 41 'tumor-free' lymph nodes from 23 patients
      with adenocarcinoma of the papilla of Vater who underwent curative tumor
      resection (R0) were examined by immunohistochemistry with the monoclonal anti
      EpCAM antibody Ber-EP4 for minimal disseminated tumor cells. RESULTS: Twelve
      (29.3%) of the 41 'tumor-free' lymph nodes obtained from 9 (39.1%) of the 23
      patients displayed EpCAM-positive cells. Kaplan-Meier survival analysis revealed
      that patients with EpCAM-positive cells in lymph showed a clearly reduced relapse
      free and overall survival compared with patients without such cells. However,
      these differences were not statistically significant (p = 0.13 for relapse-free
      survival, p = 0.11 for overall survival). DISCUSSION: Immunohistochemical
      assessment may refine the staging of resected lymph nodes in patients with
      carcinoma of the papilla of Vater. However, the presence of minimal disseminated
      tumor cells in lymph nodes had no significant impact on the prognosis in these
      patients.

PMID- 18333130
TI  - Usefulness of follow-up after pancreatoduodenectomy for carcinoma of the ampulla
      of Vater.
AB  - BACKGROUND: The prognosis for carcinoma of the ampulla of Vater (CAV) is better
      than for pancreatic cancer. The 5-year survival median rate after resection of
      CAV is 45%, but late recurrences remain possible. Several survival factors have
      been identified (lymph nodes, perineural invasion), but few data are available on
      the type of recurrences, their impact and their management. PATIENTS AND METHODS:
      A total of 41 patients treated by pancreatoduodenectomy (PD) for CAV from 1980 to
      2003 were studied retrospectively. Patient selection, long-term survival
      recurrence rate and recurrence treatment were reviewed. Univariate and
      multivariate proportional hazards analysis were conducted on this series.
      RESULTS: The mean follow-up was 48 months. Five-year survival was 62.8%. Eleven
      patients had recurrences (6-67 months). Recurrence was associated with time to
      all-causes death (hazard ratio [HR] 4.3, p=0.003). Factors predictive of
      recurrence were perineural invasion (HR 5.3, p=0.02), lymph node invasion (HR
      5.3, p=0.02) and differentiation (HR 0.2, p=0.05). Three patients underwent
      surgical R0 treatment of their recurrences. Two who presented with solitary liver
      metastasis are alive and disease-free. CONCLUSIONS: Recurrence represents a
      serious threat in the prognosis of CAV after surgery. Some of these recurrences,
      in particular liver metastases, are accessible for a curative treatment. This
      finding supports the usefulness of a close and long-term follow-up after surgery
      to improve survival of patients with CAV, especially in the group of patients
      with a good prognosis.

PMID- 18333131
TI  - A novel approach to the intraoperative assessment of the uncinate margin of the
      pancreaticoduodenectomy specimen.
AB  - BACKGROUND: Currently, there is no consensus regarding the
      pancreaticoduodenectomy (PD) margins examined intraoperatively or the technical
      protocol for frozen section examination. The aim of this work was to summarize
      our experience regarding the intraoperative examination of the uncinate margin
      and to compare it with the published literature. MATERIALS AND METHODS: Our local
      protocol for the intraoperative assessment of the uncinate margin of the PD
      specimen is described in this article. A PubMed search limited to English
      language publications using terms along the theme of pancreaticoduodenectomy and
      margin was performed. Retrieved articles were categorized according to whether
      they discussed frozen section margin examination. RESULTS: Ten articles published
      between 1981 and 2005 were retrieved which discussed the intraoperative
      examination of PD specimens. Of the 10 articles, 5 discussed the intraoperative
      consultation for diagnostic purposes only, 2 discussed the consultation for both
      diagnostic purposes and assessment of margins, and 3 discussed intraoperative
      assessment of margins only. Of the total of five articles that discussed the
      intraoperative assessment of margins, none detailed the technical protocol for
      examining the uncinate margin. DISCUSSION: Our proposed protocol for the
      intraoperative assessment of the uncinate margin of PD specimens allows for its
      accurate evaluation and has not been described previously in the English
      literature.

PMID- 18333132
TI  - Gene expression analysis for predicting gemcitabine sensitivity in pancreatic
      cancer patients.
AB  - BACKGROUND/AIMS: Current in vitro drug sensitivity tests have limitations and
      disadvantages. This study investigated the use of gene expression data to predict
      the sensitivity of pancreatic cancers to gemcitabine. MATERIALS AND METHODS:
      Cancer cells isolated from 14 pancreatic cancer patients were tested in vitro for
      gemcitabine sensitivity using the collagen droplet drug sensitivity test (CD
      DST). On the basis of this test, 9 of the 14 cancers were identified as either
      gemcitabine-sensitive or gemcitabine-resistant. Total RNA was extracted from each
      of those nine cancers and used as a template to synthesize Cy3-labeled cDNA.
      Pancreatic RNA extracted from six normal individuals was used as a control.
      Labeled probes were hybridized to an Atlas Glass Human 1.0 Microarray chip, after
      which the chips were washed and scanned, and the data were analyzed using
      Microsoft Excel-embedded software. The expression profiles of selected genes were
      confirmed using real-time PCR analysis. RESULTS: Statistical analysis of the
      microarray data showed that four genes were differentially expressed in
      gemcitabine-sensitive cancers: microsomal glutathione S-transferase 1 (GSTT1),
      topoisomerase II alpha (TOP2A), caspase 3, and ATP-binding cassette and subfamily
      C member 2 (ABCC2). More than 20 other genes were additionally identified as
      possible candidate genes associated with drug resistance. CONCLUSIONS: Expression
      of drug resistance-related genes appeared to predict whether a cancer was
      gemcitabine-sensitive or -resistant. Further study will enable a drug resistance
      scoring system to be established on the basis of gene expression. Such a system
      will allow more efficient application of chemotherapy.

PMID- 18333134
TI  - International Hepato-Pancreato-Biliary Association: who are we and where are we
      going?

PMID- 18333133
TI  - Videoscopic assisted retroperitoneal debridement in infected necrotizing
      pancreatitis.
AB  - Surgical intervention in patients with infected necrotizing pancreatitis
      generally consists of laparotomy and necrosectomy. This is an invasive procedure
      that is associated with high morbidity and mortality rates. In this report, we
      present an alternative minimally invasive technique: videoscopic assisted
      retroperitoneal debridement (VARD). This technique can be considered a hybrid
      between endoscopic and open retroperitoneal necrosectomy. A detailed technical
      description is provided and the advantages over various other minimally invasive
      retroperitoneal techniques are discussed.

PMID- 18333135
TI  - Radiofrequency ablation-assisted liver resection: review of the literature and
      our experience.
AB  - BACKGROUND: Surgical resection is the best established treatment known to provide
      long-term survival and possibility of cure for liver malignancy. Intraoperative
      blood loss has been the major concern during major liver resections, and
      mortality and morbidity of surgery are clearly associated with the amount of
      blood loss. Different techniques have been developed to minimize intraoperative
      blood loss during liver resection. The radiofrequency ablation (RFA) technique
      has been used widely in the treatment of unresectable liver tumors. This review
      concentrates on the use of RFA to provide an avascular liver resection plane.
      METHODS AND RESULTS: The following review is based on two types of RFA device
      during liver resection: single needle probe RFA and the In-Line RFA device.
      CONCLUSION: Liver resection assisted by RFA is safe and is associated with very
      limited blood loss.

PMID- 18333136
TI  - The imprint of radiofrequency in the management of hepatocellular carcinoma.
AB  - BACKGROUND: This article reviews the current results of radiofrequency
      application in the management of hepatocellular carcinoma (HCC) with reference to
      the comparison between the different surgical modalities. METHOD: An electronic
      search was performed for studies on the treatment of HCC. RESULTS: Thermoablation
      by means of radiofrequency (RFA), microwave coagulation therapy (MCT) and laser
      induced thermotherapy (LITT) provides tumor necrosis with a low complication
      rate. These methods are still not predictable and it is difficult to monitor the
      extent of necrosis in a real-time manner. Combined transarterial embolization and
      RF ablation is a promising strategy for large HCCs. Radiofrequency-assisted liver
      resection is unique and has become very popular recently because it permits
      parenchymal transection with minimal blood loss. CONCLUSION: Many alternative
      techniques have been applied recently for the management of HCC but their exact
      roles need to be defined by randomized studies. Advances in technology and
      refinements in technique may provide an effective and predictable way to ablate
      liver tumors using radiofrequency devices.

PMID- 18333138
TI  - A prospective study of in-line radiofrequency ablation in hepatic parenchymal
      transection--its efficacy and complications.
AB  - BACKGROUND: Bleeding during liver transection remains a potential hazard. This
      study aims to report the efficacy and complications of in-line radiofrequency
      ablation (ILRFA)-assisted liver resection. PATIENTS AND METHODS: The blood loss
      of 25 consecutive patients who underwent ILRFA-assisted liver resection was
      obtained by weighing swabs and measuring suction jar contents during liver
      resection and calculated in ml per cm(2) of the transection surface area.
      Postoperative complications were recorded. Five clinical variables, which might
      affect blood loss, were analyzed. RESULTS: The mean blood loss during parenchymal
      dissection for the ILRFA group was 3.4+/-3.2 ml/cm(2). Three patients had intra
      abdominal collections, including one patient with bile leakage after ILRFA
      assisted liver resection. Age, gender, extent of liver resection, liver quality
      and Pringle maneuver did not demonstrate significant impact on blood loss.
      CONCLUSIONS: This study showed that ILRFA-assisted liver resection was associated
      with very low blood loss. This is likely to improve the operative safety of liver
      resection for hepatic tumors. There were no significant postoperative sequelae.

PMID- 18333139
TI  - Magnetic resonance-guided focused ultrasound surgery (MRgFUS). Four ablation
      treatments of a single canine hepatocellular adenoma.
AB  - BACKGROUND: Canine hepatocellular adenomas are benign, well-differentiated,
      primary hepatic tumors. Surgical resection is technically demanding and is
      considered a major procedure with relatively high morbidity rates. Magnetic
      resonance-guided focused ultrasound surgery (MRgFUS) uses focused ultrasonic
      energy to non-invasively create a heat-coagulated lesion deep within the body.
      This effect can be achieved in a controlled, accurate manner. The aim of this
      study was to evaluate the safety, accuracy and efficacy of non-invasive focal
      ablation of tissue volumes of a canine benign liver tumour by consecutive MRgFUS
      sonications. MATERIALS AND METHODS: Four MRgFUS procedures were performed in a 10
      year-old, male, mixed large breed dog (45 kg) under general anaesthesia. The
      exact location and volume of the ablated areas were planned on the MR images.
      Real-time MR imaging and temperature mapping enabled the immediate evaluation of
      the effect of each sonication. Different areas were chosen within the tumour.
      These volumes of tumoral tissue were ablated by multiple sonications. To allow
      accurate targeting and quality imaging, sonications were performed during 20-30 s
      of apnoea. Between the sonications the dog was normally ventilated. The dog was
      operated 21 days after the fourth ablative procedure. The tumour was resected and
      histopathologically examined. RESULTS: The MRgFUS created necrosis with
      contiguous areas of complete tissue destruction within the liver tumour, in full
      accordance with the planning. A focal thermal injury to the cartilage of the
      right lower ribs was noted after the fourth treatment. This lesion became
      infected and was treated surgically. Ten months after the last treatment the dog
      is well and healthy. CONCLUSIONS: Focused ultrasound ablation of liver tumoral
      tissue with MR guidance under general anaesthesia and controlled apnoea is a safe
      and accurate treatment modality. Its main advantage is that it is a completely
      non-invasive image-guided treatment. The ablation of significant volumes of a
      highly vascular liver tumoral tissue was achieved. Such tissue can be ablated in
      a very accurate manner, exactly according to the pretreatment planning on the MR
      images. The MR imaging characteristics, including real-time temperature mapping,
      enable real-time control of every step of the ablation process. Mechanical
      ventilation with intermittent apnoea periods overcomes the problem of the
      respiratory movements of the liver. Care must be taken to avoid the passage of
      the ultrasound beam through energy-absorbing calcified tissue.

PMID- 18333137
TI  - Review of experimental animal models of acute pancreatitis.
AB  - The underlying mechanisms involved in the pathogenesis of acute pancreatitis are
      ill understood. The mortality rate of this disease has not significantly improved
      over the past few decades. Current treatment options are limited, and
      predominantly aimed at supportive therapy. A key feature of severe acute
      pancreatitis is the presence of extensive tissue necrosis with both local and
      systemic manifestations of inflammatory response syndromes. A better
      understanding of the underlying pathophysiology of severe acute pancreatitis may
      lead to more targeted therapeutic options, potentially leading to improved
      survival. Animal models of acute pancreatitis are therefore an essential
      investigative tool for these aims to be achieved. This review discusses the
      suitability of recent non-invasive models of acute pancreatitis such as hormone
      induced, alcohol-induced, immune-mediated, diet-induced, gene knockout and L
      arginine; and invasive models including closed duodenal loop, antegrade
      pancreatic duct perfusion, biliopancreatic duct injection, combination of
      secretory hyperstimulation with minimal intraductal bile acid exposure, vascular
      induced, ischaemia/reperfusion and duct ligation.

PMID- 18333140
TI  - Management of adult choledochal cysts--a 15-year experience.
AB  - BACKGROUND: Choledochal cyst, a common surgical problem of childhood, can have a
      delayed presentation in adults. The clinical course in adults differs from that
      in children because of a higher incidence of associated hepatobiliary pathology.
      METHODS: The clinical data of 57 adults with choledochal cyst managed in a
      general surgical unit between January 1988 and March 2003 were analysed. RESULTS:
      The male:female ratio was 1:1.38 and the mean age was 34.5 years; 71.9% of the
      cysts belonged to Todani type I, 26.3% to type IV and 1.8% to type V. Abdominal
      pain and recurrent cholangitis were the commonest presentations followed by acute
      pancreatitis, palpable mass and bronchobiliary fistula. Anomalous
      pancreaticobiliary ductal junction was demonstrated in 14% of the cases. In all,
      37% of the patients had undergone either wrong or suboptimal surgical procedures
      prior to presentation. All patients underwent complete excision of the cyst and
      hepaticojejunostomy. Two patients required cholangiojejunostomy and three
      patients required resection of the involved segments of the liver in addition.
      There were three anastomotic leaks and two postoperative deaths. Two anastomotic
      leaks resolved spontaneously while the third required surgical intervention.
      Forty-eight patients were available for follow-up and have remained symptom-free
      over a mean period of 17.6 months. CONCLUSIONS: Choledochal cyst should be
      considered in all patients below 40 years of age presenting with biliary colic,
      pancreatitis or recurrent cholangitis with associated dilatation of bile duct.
      Complete excision of the cyst with restoration of biliary-enteric communication
      by hepaticojejunostomy form the basis of ideal treatment.

PMID- 18333141
TI  - Laparoscopic treatment of biliary hepatic cysts: short- and medium-term results.
AB  - BACKGROUND: The aim of this study was to evaluate the postoperative morbidity
      and, in the medium-term results, the incidence of relapses in the laparoscopic
      treatment of non-parasitic hepatic cysts (NPHC) and polycystic liver disease
      (PCLD). PATIENTS AND METHODS: From 1999 to 2003, 12 patients with NPHC and 3
      patients with PCLD with few large cysts in the anterior hepatic segments
      underwent laparoscopic fenestration and deroofing. RESULTS: There were no
      conversions and no mortality; the mean operative time was 55 min for NPHC and 120
      min for PCLD. Postoperative morbidity comprised two patients with
      bronchopneumonic infiltrations and in one patient with PCLD ascites resolved
      spontaneously. All the patients experienced resolution of the symptomatology.
      Follow-up was carried out from 3 to 38 months (mean 18 months). There was no
      relapse of the disease. DISCUSSION: The preoperative selection of patients is
      fundamental to program the surgical treatment. Laparoscopy can be considered a
      safe and efficacious treatment for NPHC and PCLD.

PMID- 18333142
TI  - Utility of 3D magnetic resonance imaging in preoperative evaluation of
      hepatobiliary diseases.
AB  - Three-dimensional (3D) imaging is playing an increasingly important role in
      modern diagnostic radiology. The recent improvements in magnetic resonance (MR)
      hardware, scanning protocols and 3D volumetric reconstruction software have
      facilitated great expansion of the role of 3D imaging for use in hepatobiliary
      surgery. In this review, we address the various 3D reconstruction techniques used
      in MRI and demonstrate the value of 3D imaging in preoperative evaluation of
      hepatobiliary diseases.

PMID- 18333143
TI  - Pseudoaneurysm of cystic artery after laparoscopic cholecystectomy.
AB  - BACKGROUND: The formation of a pseudoaneurysm of the cystic artery is a rare
      occurrence after laparoscopic cholecystectomy. CASE OUTLINE: Seven weeks after
      laparoscopic cholecystectomy, a 31-year-old woman presented with a picture of
      obstructive jaundice. The diagnosis of cystic artery aneurysm was verified by
      arteriography, CT and MRCP. At laparotomy the pseudoaneurysm was found to be
      compressing the common bile duct. It was successfully managed by ligation of the
      right hepatic artery. DISCUSSION: Although this complication is rare, the surgeon
      must have a high index of suspicion to make the diagnosis.

PMID- 18333144
TI  - Pancreatic cystic neoplasia.

PMID- 18333146
TI  - Minimising blood loss and transfusion requirements in hepatic resection.
AB  - BACKGROUND: Substantial blood loss and the requirement for blood transfusion
      remain major considerations for hepatic surgeons. We analysed the impact of a
      systematic protocol aimed at reducing intraoperative blood loss and homologous
      blood (HB) transfusion associated with hepatic resection. METHODS: Prospective
      clinical data were collected from 151 elective liver resections performed during
      the period between 1980 and 1999. Further data directly related to blood loss and
      anaesthesia were retrospectively collected from the anaesthetic intra-operative
      record. Strategies implemented in 1991 included preoperative autologous blood
      donation, low central venous pressure anaesthesia, aprotinin administration,
      ultrasonic dissection, hepatic vascular inflow occlusion and a Cell Saver. Blood
      loss and transfusion requirements were studied before and after the
      implementation of these strategies. RESULTS: There was no difference in the
      patient demographics, indications for operation or the scope of resections in the
      two time periods evaluated. Blood-saving strategies resulted in decreased
      estimated blood loss (4500 mL vs. 1000 mL p<0.001). In addition, the number of
      patients requiring transfusion decreased (91.8% vs. 25.5% respectively, p<0.001)
      and the mean number of units of HB transfusion was lower (I 3.7 vs. 2.3,
      p<0.001). Morbidity and mortality were also decreased (57.1% vs. 25.5%, p<0.001
      and 10.2% and 4.9% p<0.001, respectively). No complications directly referrable
      to low CVP anesthesia were identified. CONCLUSION: Systematic implementation of
      strategies designed to control blood loss are effective and may reduce morbidity
      and mortality associated with hepatic resections.

PMID- 18333147
TI  - Alterations of tumor necrosis factor-alpha and interleukin 6 production and
      activity of the reticuloendothelial system in experimental obstructive jaundice
      in rats.
AB  - BACKGROUND: Immunological changes are well recognised in obstructive jaundice.
      The aim of this study was to monitor plasma tumor necrosis factor alpha (TNF
      alpha) and interleukin-6 (IL-6) levels in rats with obstructive jaundice.
      METHODS: The ability of splenocytes and peritoneal exudate cells (PEC) to produce
      these cytokines both spontaneously and on induction with lipopolysaccharide
      (LPS), was compared in rats with and without obstructive jaundice (OJ). The
      activity of the reticuloendothelial system (RES) was also measured. RESULTS:
      Serum cytokine levels in OJ rats were higher than in control rats. PEC cultures
      produced significantly more IL-6, compared with control rats, declining
      thereafter. TNF-alpha activity in the splenocyte cultures of OJ rats was also
      higher than in the control group. Pronounced differences were found in the
      ability to produce TNF-alpha by PEC, i.e., TNF-alpha production was much stronger
      on day 7 in OJ rats than in controls. On day 14 TNF-alpha production was much
      lower and the spontaneous response was equal to the LPS-induced one. On day 21
      the cells of OJ rats partially regained the ability to produce TNF-alpha RES
      activity of OJ rats was significantly suppressed in the liver and spleen, whereas
      the phagocytic activity in the lungs was elevated. CONCLUSION: We have
      demonstrated that the immune reactivity of OJ rats, initially elevated, underwent
      subsequent depression. The study also revealed a major effect of the operation
      alone on the studied parameters.

PMID- 18333148
TI  - Preoperative portal vein embolisation for primary and metastatic liver tumours:
      volume effects, efficacy, complications and short-term outcome.
AB  - BACKGROUND: The aim of portal vein embolisation is to induce hyperplasia of
      normal tissue when resection of a cancerous portion of the liver is
      contraindicated only by the volume of liver that would remain following
      operation. METHODS: Eight patients with inoperable liver tumours (3 women and 5
      men, median age 69.5 years, 3 colorectal hepatic metastasts, 2
      choloangiocarcinomas and 3 hepatocellular cancers) were selected for portal vein
      embolisation. Selected portal branches were occluded with microparticles and
      coils. Liver volumes were determined by magnetic resonance imaging (MRI) before
      embolisation and again before operation. RESULTS: Embolisation was successfully
      performed in all 8 patients, 7 by the percutaneous-transhepatic route, while one
      patient required open cannulation of a mesenteric vein. Management was altered in
      6 patients who proceded to 'curative' resection; projected remaining liver
      volumes increased (Wilcoxon's matched pairs test p=0.02) from a median of 361 cc
      to a median of 550 cc; two patients had disease progression such that operation
      was no longer indicated. In one patient a misplaced coil unintentionally occluded
      a portal branch to normal liver. CONCLUSIONS: Portal vein embolisation produced
      appreciable hyperplasia of the normal liver and extended the option of 'curative'
      operation to 6 out of the 8 cases attempted. Complications can occur. The long
      term results following operation are unknown.

PMID- 18333149
TI  - Gastroduodenal ulceration following hepatic arterial chemotherapy: the role of
      methylene blue endoscopy in the investigation of pain.
AB  - BACKGROUND: Unintended perfusion of the gastroduodenum may complicate hepatic
      arterial chemotherapy leading to mucosal ulceration. PATIENTS AND METHODS: In a
      review of 233 consecutive hepatic artery catheters placed, 61 patients were
      investigated for chemotherapy-related epigastric pain. Investigations included
      catheter imaging, upper gastrointestinal endoscopy with methylene blue injection
      via the hepatic artery catheter and angiography. RESULTS: Twenty patients (33%)
      demonstrated blue staining of the gastroduodenum. Angiography performed in 15 of
      these patients confirmed a misperfusing vessel in 13.The aberrant artery was
      successfully embolised and infusional chemotherapy recommenced in 11 patients.
      Forty-one patients had a negative dye test, of whom three had gastroduodenal
      ulcers, 14 had oesophagitis or gastroduodenitis, ten had catheter complications
      (leak n=2, arteritis n=5, pseudoaneurysm n=1, sepsis n=1), three had liver
      collections, five had floxuridine cholangitis and one had myocardial ischaemia.
      No cause could be found in 8 patients. No patient with a negative dye test
      developed unintended perfusion on repeat investigation.

PMID- 18333150
TI  - Management of hepatobiliary and pancreatic disorders at the Academic Medical
      Center Amsterdam, Netherlands.

PMID- 18333151
TI  - Aberrant gallbladder situated beneath the left lobe of liver.
AB  - BACKGROUND: Aberrant gallbladder beneath the left liver is a rare congenital
      anomaly that is found in 0.1-0.7 per cent of the population and causes confusion
      on imaging and at operation.Two such cases are presented. CASE OUTLINES: A man of
      83 yr was explored for obstructive jaundice due to a hilar tumour, but the
      gallbladder was 'missing'. Exploration of a cystic mass to the left of the
      falciform ligament revealed a gallbladder attached to segment III of the liver.
      Laparotomy for gallstones in a woman of 70 yr failed to reveal the gallbladder
      until further dissection was carried out to the left of the falciform ligament.
      In each of these cases the cystic duct described a hairpin bend before joining
      the common hepatic duct on its right-hand side. CONCLUSION: A left-sided
      gallbladder can be truly ectopic or may just appear so because the falciform
      ligament is aberrantly placed to the right. In either case preoperative imaging
      can be misleading, and a careful search is needed at operation. The incidence of
      disease seems no commoner than in orthotopic gallbladders.

PMID- 18333152
TI  - Liver tumours due to endometriosis and endometrial stromal sarcoma.
AB  - BACKGROUND: Endometriosis can occur in unusual sites, liver involvement being
      first described in 1986. Extra-uterine malignant transformation in endometriosis
      has been reported, occurring mainly in the ovary. Liver involvement with
      endometrial stromal sarcoma (ESS) has not been previously reported. CASE OUTLINE:
      Two patients presenting with symptomatic liver masses related to endometriosis,
      who successfully underwent surgical intervention, are presented. CASE 1: A 31
      year-old woman previously had been treated with hysterectomy and bilateral
      salpingoophorectomy for severe pelvic endometriosis. Six years later, she
      presented with malaise from bilobar liver involvement with endometrial deposits.
      She proceeded acutely to hilar obstruction with obstructive jaundice and portal
      vein thrombosis. CASE 2: A 59-year-old post-menopausal woman had earlier
      presented acutely from a ruptured mesenteric cyst, which showed features of
      endometrial stromal sarcoma (ESS). Two years later, she presented with symptoms
      from a large ESS occupying the right lobe. DISCUSSION: Endometriosis per se, as
      well as malignant transformation into ESS can involve the liver.These should be
      considered in women with hepatic space occupying lesions of unknown etiology.

PMID- 18333155
TI  - Hepatocellular carcinoma.

PMID- 18333153
TI  - Metastatic carcinoid tumour presenting as hepatic encephalopathy.
AB  - BACKGROUND: Hepatic encephalopathy is rarely encountered with carcinoid syndrome,
      but massive hepatic replacement by carcinoid tumour can cause neuropsychiatric
      alterations. CASE OUTLINE: A man of 42 years presented with carcinoid syndrome
      accompanied by features of hepatic encephalopathy. Following extended right
      hepatectomy his mental status returned to normal in line with markers of hepatic
      failure. CONCLUSION: Extensive replacement of liver parenchyma by carcinoid
      tumours can lead to hepatic dysfunction as circulating levels of unmetabolised
      ammonia rise secondary to porto systemic shunting.

PMID- 18333156
TI  - Epidemiology and carcinogenesis of hepatocellular carcinoma.
AB  - The incidence of hepatocellular carcinoma (HCC) shows marked variation worldwide
      but the magnitude of this tumor is reflected by the occurrence of at least 1
      million new cases annually and the uniformly dismal outlook with median survivals
      of <25 months after resection and <6 months with symptomatic treatment. The
      strikingly uneven distribution of this tumor parallels the prevalence of
      hepatitis B infection with rising incidence in western countries attributed to
      hepatitis C infection. Chronic hepatitis and cirrhosis constitute the major
      preneoplastic conditions in the majority of HCCs and may be related to other
      etiologic agents such as environmental chemical carcinogens including nitrites,
      hydrocarbons, solvents, organochlorine pesticides, and the chemicals in processed
      foods, cleaning agents, cosmetics and pharmaceuticals, as well as plant toxins
      such as anatoxins produced by fungi that cause spoilage of grain and food in the
      tropics. Genetic diseases such as genetic hematochromatosis, Wilson's disease,
      alpha-1-antitrypsin deficiency, and the inborn errors of metabolism including
      hereditary tyrosinemia and hepatic porphyria, are known to be associated with
      HCC. Numerous genetic alterations and the modulation of DNA methylation are
      recognized in HCC and it is likely that these genetic and epigenetic changes
      combine with factors involved in chronic hepatocyte destruction and regeneration
      to result in neoplastic growth and multiple molecular pathways may be involved in
      the production of subsets of hepatocellular tumors.

PMID- 18333157
TI  - Prevention of hepatocellular carcinoma.

PMID- 18333159
TI  - Staging systems in hepatocellular carcinoma.
AB  - Staging systems are key to predict the prognosis of patients with cancer, to
      stratify the patients according to prognostic variables in the setting of
      clinical trials, to allow the exchange of information among researchers, and
      finally to guide the therapeutic approach. The current knowledge of the disease,
      however, prevents recommendation of a staging system that can be used world-wide.
      The conventional staging systems for hepatocellular carcinoma (HCC), such as the
      Okuda stage or the TNM stage have shown important limitations in classifying
      patients. Several new systems have been proposed recently, and only three of them
      have been validated at this point. The BCLC staging classification links the
      stage of the disease to a specific treatment strategy. The JIS score has been
      proposed and used in Japan, although it needs Western validation. The CLIP score
      is used in patients with advanced tumors. Several reasons explain the difficulty
      in identifying a world-wide system. First, HCC is a complex neoplasm inserted on
      a pre-neoplastic cirrhotic liver, and thus variables of both diseases leading to
      death should be taken into account. Second, the disease is very heterogeneous
      around the world, and this reflects different underlying epidemiological
      backgrounds and risk factors. Third, HCC is the sole cancer treated by
      transplantation in a small proportion of patients. Fourth, only around 20% of the
      cases are currently treated by surgery, thus precluding the wide use of pathology
      based systems, such as TNM. Finally, the potential relevance of a molecular
      signature identified in terms of outcome prediction is unknown, and further
      research is needed to obtain this valuable biological information that may aid in
      classifying the patients.

PMID- 18333158
TI  - Diagnosis of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is responsible for a large proportion of cancer
      deaths worldwide. HCC is frequently diagnosed after the development of clinical
      deterioration at which time survival is measured in months. Long-term survival
      requires detection of small tumors, often present in asymptomatic individuals,
      which may be more amenable to invasive therapeutic options. Surveillance of high
      risk individuals for HCC is commonly performed using the serum marker alpha
      fetoprotein (AFP) often in combination with ultrasonography. Various other
      serologic markers are currently being tested to help improve surveillance
      accuracy. Diagnosis of HCC often requires more sophisticated imaging modalities
      such as CT scan and MRI, which have multiphasic contrast enhancement
      capabilities. Serum AFP used alone can be helpful if levels are markedly
      elevated, which occurs in fewer than half of cases at time of diagnosis.
      Confirmation by liver biopsy can be performed under circumstances when the
      diagnosis of HCC remains unclear.

PMID- 18333160
TI  - Surgical treatment of hepatocellular carcinoma.
AB  - Surgery for hepatocellular carcinoma (HCC) includes partial liver resection (LR)
      and liver transplantation (LT). Although LT represents the most efficient
      treatment in patients with small HCC, <30% of patients are eligible for LT
      because of restrictive criteria (one nodule <5 cm or two to three nodules <3 cm
      without macroscopic vascular invasion), graft unavailability and the high cost of
      the procedure. For large HCC, LR remains the only potential curative treatment.
      LR is now safer, with a low rate of mortality. Selective preoperative
      morphological assessment, preoperative use of portal vein embolization for
      increasing future remnant liver volume and the improvement of surgical techniques
      such as the use of intermittent clamping and anterior approach are factors that
      improve the safety and tolerance of LR. In patients with small HCCs and a
      preserved liver function (Child-Pugh grade A), good long-term survival can be
      achieved after anatomical resection that removes the tumor(s) and its portal vein
      territory. These good results of LR for small HCC and the increasing duration of
      the waiting list for candidates of LT have renewed the place of LR as a bridge
      treatment before LT.

PMID- 18333161
TI  - Non-surgical treatment of hepatocellular carcinoma.
AB  - A wide variety of non-surgical therapies can result in clinical responses in
      patients with hepatocellular carcinoma. Two recent studies have suggested that
      transarterial chemoembolisation can, in highly selected patients with good liver
      function, result in an improvement in survival. No other approaches have, to
      date, demonstrated convincing evidence of survival advantage.

PMID- 18333163
TI  - Hepatic encephalopathy verified by psychometric testing and EEG in cirrhotic
      patients: effects of mesocaval interposition shunt or sclerotherapy.
AB  - BACKGROUND: The aim of this randomised prospective study was to evaluate hepatic
      encephalopathy after mesocaval interposition shunt operation and after repeated
      endoscopic sclerotherapy. METHODS: Forty-five patients with bleeding oesophageal
      varices due to liver cirrhosis were randomised to the two treatment groups, 24 to
      the shunt group and 21 to the sclerotherapy group. The patients were evaluated
      preoperatively regarding blood tests, hepatic encephalopathy as measured by
      electroencephalogram with spectral analysis and by a battery of psychometric
      tests. The direction of portal flow in the shunt group was investigated by shunt
      phlebography and ultrasonography with Doppler. During follow-up the same
      investigations were performed twice at median 6.7 and 14.7 months after
      operation. RESULTS: No statistically significant difference was found during
      follow-up regarding blood tests and electroencephalography with spectral
      analysis. Although the preoperative psychometric tests showed that the shunt
      group performed significantly better than the sclerotherapy group, the first
      follow-up showed that the shunt group performed statistically worse than the
      sclerotherapy group in seven of the tests: Synonyms (measuring verbal ability),
      Block Design Test (measuring visuo-spatial ability), Memory for Design Test,
      Error Score (measuring memory function), Revised Visual Retention Test, correct
      answers and the same test error answers (measuring visuo-spatial memory, ability
      and immediate memory), Digit Symbol Test (measuring perceptual ability) and Trial
      Making Test B (measuring cognitive motor abilities). CONCLUSIONS: Patients
      treated by mesocaval interposition shunt showed a progressive general reduction
      in psychometric performance compared with patients treated with repeated
      sclerotherapy, in whom a general intellectual improvement was observed. This
      finding corresponds to the reverse direction of the preoperative portal flow to a
      hepatofugal pattern at first follow-up and at 12 months among two-thirds of the
      patients.

PMID- 18333162
TI  - Viral hepatitis and the surgeon.
AB  - BACKGROUND: Viral hepatitis is an infection of the liver caused by one or more of
      six known (HAV-HGV) hepatotropic viruses. It is a common problem among health
      care workers and their patients. Surgeons are at particular risk of both
      acquiring and transmitting some of these viruses from and to their patients.
      Unfortunately, specific immunoprophylaxis for viral hepatitis is presently
      limited to protecting against the spread of hepatitis A and B viral infections,
      leaving a high degree of vigilance and careful surgical technique as the only
      means available to prevent the transmission of other viruses relative to the
      surgeon. The purpose of this paper is to review the various forms of viral
      hepatitis including the nature of the virus, serologic testing, clinical
      features, epidemiology (with specific reference to those issues that arise in
      surgical practice), treatment and prevention.

PMID- 18333164
TI  - Liver resection in a patient with concomitant thoraco-abdominal and cerebral
      aneurysms.
AB  - BACKGROUND: Surgical resection remains the only curative procedure for liver
      metastases but even in expert hands it has appreciable morbidity and mortality
      rates. The presence of a concomitant aortic aneurysm greatly increases these
      risks. CASE OUTLINE: A 66-year-old woman who was known to have large aneurysms of
      the thoraco-abdominal aorta and middle cerebral artery presented with colorectal
      liver metastases. After detailed preoperative assessment, she underwent resection
      of segments V and VI of the liver. The surgical procedure was uneventful. She
      made a good initial recovery, but on day 7 she suddenly became hypotensive and
      died from a cardiorespiratory arrest. Post-mortem examination revealed a ruptured
      thoracic portion of the thoraco-abdominal aortic aneurysm. CONCLUSION: Despite
      careful control of perioperative blood pressure and the lack of abdominal
      complication, intrathoracic aneurysmal rupture on day 7 highlights the risk of
      major unrelated operations in patients with aneurysmal disease.

PMID- 18333166
TI  - Pancreas summary.

PMID- 18333168
TI  - Biliary summary.

PMID- 18333169
TI  - Value of regional lymphadenectomy in pancreatic cancer.
AB  - Radical surgical resection and adjuvant chemotherapy are the goal standard to
      attempt significant long term survival in patients suffering from ductal
      pancreatic cancer. The role of extended lymph-node dissection is still a debated
      issue. In this paper a deep review of the experiences reported in the literature
      is carried out. Several studies are limited, not randomized and retrospective:
      generally speaking they seem to suggest a positive role in node dissection.
      Unfortunately, this trend is not confirmed in the only two trials conducted in a
      prospective and randomized setting. Moreover the results of these studies are
      also difficult to compare. At the moment we can say that extended lymphadenectomy
      does not play a determinant role for long term survival but a positive trend has
      been shown for node positive patients.

PMID- 18333170
TI  - Distal pancreatectomy: en-bloc splenectomy vs spleen-preserving pancreatectomy.
AB  - Distal pancreatectomy with en-bloc splenectomy has been considered the standard
      technique for management of benign and malignant pancreatic disorders. However,
      splenic preservation has recently been advocated. The aim of this study was to
      review the experiences of distal pancreatectomy using the open or the
      laparoscopic approach and to critically discuss the need to perform splenectomy.
      Original articles published in the English literature of peer-reviewed medical
      journals were selected for detailed analysis. In patients with malignant
      neoplasms in the body-tail of the pancreas, splenectomy has a negative influence
      on long-term survival after resection. The incidence of diabetes after spleen
      preserving distal pancreatectomy for chronic pancreatitis is less than after en
      bloc splenectomy. Spleen salvage eliminates the risk of overwhelming infections.
      Laparoscopic spleen-preserving distal pancreatectomy is feasible and safe.
      Laparoscopic spleen-preserving distal pancreatectomy may be preferable for the
      advantages of a minimally invasive approach.

PMID- 18333172
TI  - The role of chemoradiation therapy in locally advanced pancreatic cancer.
AB  - The majority of patients with pancreatic cancer present with disease that is
      unresectable due to local invasion. This article reviews the evidence (or lack
      thereof) that chemoradiation therapy (CRT) helps these patients in four areas:
      survival, tumor downstaging, palliation of obstructive symptoms, and pain
      control. We believe that CRT allows a small percentage of patients with locally
      advanced disease to undergo potentially curative resection while providing
      effective palliative treatment.

PMID- 18333171
TI  - Complications of pancreatic surgery.
AB  - Pancreatic resection is the only treatment option that can lead to a meaningful
      prolonged survival in pancreatic cancer and, in some instances, perhaps a
      potential chance for cure. With the advent of organ and function preserving
      procedures, its use in the treatment of chronic pancreatitis and other less
      common benign diseases of the pancreas is increasing. Furthermore, over the past
      two decades, with technical advances and centralization of care, pancreatic
      surgery has evolved into a safe procedure with mortality rates of <5%. However,
      postoperative morbidity rates are still substantial. This article reviews the
      more common procedure-related complications, their prevention and their
      treatment.

PMID- 18333173
TI  - Surgical treatment of chronic pancreatitis with pancreatic main duct dilatation:
      long term results after head resection and duct drainage.
AB  - Tissue and duct hypertension is considered as a major factor in the etiology of
      pain in patients with chronic pancreatitis (CP). Duct dilatation is a consequence
      of duct obstruction due to scars or duct stones. Nevertheless, the procedure of
      choice, drainage or resection, is still under discussion. We present long-term
      results of patients operated with duodenum-preserving pancreatic head resection
      (DPPHR) combined with a Partington-Rochelle duct drainage in cases of chronic
      pancreatitis with multiple stenosis and dilatation of the side ducts. METHODS AND
      PATIENTS: From April 1982 to September 2001, in 55 out of 538 patients with
      chronic pancreatitis, a DPPHR with additionally Partington-Rochelle duct drainage
      was performed (44 male, 11 female, mean age 45.8 years). Ninety-two percent of
      the patients suffered from alcoholic pancreatitis. Medical respective pain
      treatment for chronic pancreatitis was in median 64.5 months prior to surgery.
      The indications for surgery were in 87% pain, 59% of the patients had an
      inflammatory mass in the head of the pancreas, 36% a common bile duct stenosis
      and 5% a severe stenosis of the duodenum. The endocrine function (OGGT) was
      impaired in 79% of the patients preoperatively. RESULTS: Hospital mortality was
      0%, postoperative complications occurred in 11 patients. FOLLOW-UP: All except 2
      patients were followed up in the outpatient clinic with the mean follow-up time
      of 69.7 months (8-105 months), the late mortality was 9%. Sixty-eight percent of
      the patients were completely free of pain, 29% had occasional pain, 3% suffered
      from a further attack of pancreatitis. Body weight increased in 79%, 58% were
      professionally rehabilitated. Late postoperative endocrine function was unchanged
      in 85% (improved in 5%, deteriorated in 10%). CONCLUSION: The pain control in
      patients with multiple duct stenosis after duodenum-preserving pancreatic head
      resection with duct drainage leads to long-standing absence of pain and low
      recurrence rate of attacks of pancreatitis.

PMID- 18333174
TI  - Trends in fungal colonization of pancreatic necrosis in patients undergoing
      necrosectomy for acute pancreatitis.
AB  - BACKGROUND: This study examines fungal colonization of post-inflammatory
      pancreatic necrosis in a cohort of patients undergoing open surgical necrosectomy
      in a single, tertiary referral unit over a 10-year period. METHODS: The charts of
      all patients with acute pancreatitis who underwent surgical necrosectomy during
      the period January 1992 to December 2001 were examined. Following exclusions a
      population of 30 patients were identified. There were 18 men with a median
      (range) age of 42 (20-69) years. Sixteen (53%) underwent surgery because of
      positive fine needle aspirates and the remainder underwent surgery on clinical
      grounds. Twenty-nine (97%) received antibiotics prior to necrosectomy. Principal
      outcomes were the results of microbiological culture with reference to isolation
      of fungi, site of isolates, trends in colonization and outcome. RESULTS: Candida
      were cultured from pancreatic necrosis in 5 (17%). These 5 individuals also had
      positive candidal cultures from sputum or bronchial aspirates. There were no
      deaths in patients with fungal colonization of necrosis. There was no change in
      the annual incidence of fungal colonization of necrosis over the study period.
      CONCLUSION: Although this is a small study, there are two consistent
      observations: mortality in fungal colonization of necrosis was low and there was
      no change in the annual incidence of fungal colonization of necrosis over the
      decade. Discrepancies between these findings and those of previous reports
      mandate larger prospective evaluation.

PMID- 18333175
TI  - Exercise-induced cholangitis and pancreatitis.
AB  - BACKGROUND: Cholangitis requires bactibilia and increased biliary pressure.
      Pancreatitis may be initiated by elevated intraductal pressure. The sphincter of
      Oddi regulates pancreatobiliary pressures and prevents reflux of duodenal
      contents. However, following biliary bypass or pancreatoduodenectomy, increased
      intra-abdominal pressure may be transmitted into the bile ducts and/or pancreas.
      The aim of this analysis is to document that cholangitis or pancreatitis may be
      exercise-induced. METHODS: The records of patients with one or more episodes of
      cholangitis or pancreatitis precipitated by exercise and documented to have
      patent hepatico- or pancreatojejunostomies were reviewed. Cholangitis was defined
      as fever with or without abdominal pain and transiently abnormal liver tests.
      Pancreatitis was defined as abdominal pain, with transient elevation of serum
      amylase and documented by peripancreatic inflammation on computerized tomography.
      RESULTS: Twelve episodes of cholangitis occurred in six patients who had
      undergone hepaticojejunostomy for biliary stricture (N=3), Type I choledochal
      cyst (N=2), or pancreatoduodenectomy for renal cell carcinoma metastatic to the
      pancreas (N=1). Four episodes of pancreatitis occurred in two patients who had
      undergone pancreatoduodenectomy for ampullary carcinoma or chronic pancreatitis.
      Workup and subsequent follow-up for a median of 21 months have not documented
      anastomotic stricture. Each episode of cholangitis and pancreatitis was brought
      on by heavy exercise and avoidance of this level of exercise has prevented future
      episodes. CONCLUSION: Following biliary bypass or pancreatoduodenectomy,
      significant exercise may increase intra-abdominal pressure and cause cholangitis
      or pancreatitis. Awareness of this entity and behavior modification will avoid
      unnecessary procedures in these patients.

PMID- 18333176
TI  - Analysis of long-term survivors after surgical resection for invasive pancreatic
      cancer.
AB  - Pancreatic cancer remains a lethal disease. Although there are many reports on
      the survival rates of pancreatic cancer patients after surgical resection, the
      clinicopathological characteristics that influence long-term survival over 5
      years remain controversial. Here, we clarify the favourable prognostic factors
      for long-term survival. One hundred and eighty-two patients with pancreatic
      cancer underwent surgical resections from 1981 to 1997 in our department. Among
      them, eight patients survived for at least 5 years after the surgery. The
      clinicopathological characteristics of the eight long-term survivors who
      underwent radical resections were studied retrospectively. R0 surgical
      resections, including five combined with portal vein resections (62.5%), were
      achieved in these eight patients. Negative invasions of the major regional artery
      (seven of eight, 87.5%) and to the extrapancreatic nerve plexus (seven of eight,
      87.5%), and N0 or Nl lymph node metastasis (7 of 8, 87.5%) were detected as
      clinicopathological features of long-term survivors in our study. No exposure of
      carcinoma at the dissected surface and cut end (seven of eight, 87.5%) was
      characteristically confirmed by pathology. Portal vein invasion was seen in three
      of the eight patients (37.5%). For long-term survival in cases of pancreatic
      cancer, complete R0 resections should be performed and negative invasions in the
      major regional arteries and to the extrapancreatic plexus of the nerve were
      necessary. No invasion to the portal vein was not necessarily required if R0 was
      achieved by combined resection of the portal vein.

PMID- 18333177
TI  - Frozen section and permanent diagnoses of the bile duct margin in gallbladder and
      bile duct cancer.
AB  - HYPOTHESIS: Frozen section diagnosis and permanent diagnosis of bile duct margin
      predict local recurrence after surgical resection of gallbladder or bile duct
      carcinoma. DESIGN: Retrospective review. SETTING: University, tertiary care.
      PATIENTS: A total of 20 patients underwent frozen section diagnosis of bile duct
      margin for resection of gallbladder and bile duct carcinoma. MAIN OUTCOME:
      Diagnosis of frozen and permanent section of bile duct margin, and local
      recurrence. RESULTS: The permanent diagnosis was identical in 15 patients but
      changed in 5 (from positive to negative in 3 and from negative to positive in 2).
      The reasons for these changes were overdiagnosis (mucosal lesions in two and
      mesenchymal components in another) and new recognition of malignant cells on
      permanent section in the other two. In seven patients with a positive bile duct
      margin by permanent histology, mucosal spread was evident in two and involvement
      of the subepithelial layer was present in the other five. No local recurrence
      occurred in the two patients with epithelial spread and four of the five with
      subepithelial infiltration. CONCLUSIONS: Frozen section and permanent diagnoses
      of the bile duct margin in gallbladder and bile duct carcinoma may be
      inconsistent in 25% of patients due to overdiagnosis of frozen section or new
      recognition of cancer cells by permanent histology. In situ carcinoma does not
      always produce local recurrence, while cancer cells in the subepithelial layer
      strongly predict occurrence of local recurrence.

PMID- 18333178
TI  - Diminished gallbladder motility in Rotund leptin-resistant obese mice.
AB  - BACKGROUND: Obesity is a risk factor for cholesterol gallstone formation, but the
      pathogenesis of this phenomenon remains unclear. Most human obesity is associated
      with diabetes and leptin-resistance. Previous studies from this laboratory have
      demonstrated that diabetic leptin-resistant (Lep(db)) obese mice have low biliary
      cholesterol saturation indices, enlarged gallbladders and diminished gallbladder
      response to neurotransmitters. Recently, a novel leptin-resistant mouse strain
      Lepr(db-rtnd) (Rotund) has been discovered. Rotund mice are also obese, diabetic,
      and have an abnormal leptin receptor. Therefore, we tested the hypothesis that
      leptin-resistant obese Rotund mice would have large gallbladders and reduced
      biliary motility. METHODS: Eight-week-old control (C57BL/6J, N=12) and Rotund
      leptin-resistant (Lepr(db-rnd), N=9) mice were fed a non- lithogenic diet for
      four weeks. Animals were fasted and underwent cholecystectomy. Gallbladder
      volumes were recorded, and contractile responses (N/cm(2)) to acetylcholine (10(
      5) M), Neuropeptide Y (10(-8,-7,-6) M), and cholecystokinin (10(-10,-9,-8,-7) M)
      were measured. Results were analyzed using the Mann-Whitney Rank Sum Test.
      RESULTS: Compared to control mice, Rotund mice had larger body weights, higher
      serum glucose levels, and greater gallbladder volumes (p<0.05). Rotund
      gallbladders had less contractility (p<0.05)) to acetylcholine and
      cholecystokinin than control mice. Responses to Neuropeptide Y were also less,
      but not statistically significant, in the Rotund mice. CONCLUSIONS: These data
      suggest that leptin-resistant Rotund mice have (1) enlarged gallbladders with (2)
      diminished contractility compared to lean control mice. Therefore, this study
      confirms that leptin-resistance is associated with abnormal biliary motility and
      may lead to gallstone formation in leptin-resistant obesity.

PMID- 18333179
TI  - Resistant pathogens in biliary obstruction: importance of cultures to guide
      antibiotic therapy.
AB  - BACKGROUND: Cholangitis, infection of the bile ducts, is a serious condition that
      necessitates prompt and efficacious treatment for a good clinical outcome. A
      single center retrospective study of cholangitis was conducted to better define
      the spectrum of responsible pathogens and their antibiotic sensitivities.
      METHODS: We studied all patients at our hospital who had cholangitis from January
      1998 to June 2004. Patients were identified by ICD-9 codes and the cause of the
      cholangitis, the treatment and culture data were noted by review of the medical
      record. RESULTS: Thirty patients presented with cholangitis as noted by the
      clinical symptoms of jaundice, fever and abdominal pain. The cause of the biliary
      obstruction was gallstones in 18 patients, benign biliary strictures in 5 and
      malignant obstruction in 7. All the patients with malignant obstruction with
      cholangitis had stents; there were no cases of cholangitis in malignant
      obstruction unless prior instrumentation had been performed. The most common
      isolates were Enterococcus>E. coli>Enterobacter>Klebsiella. Sixty-four percent of
      blood cultures and all but one of the bile cultures grew organisms. Seventy-two
      percent of patients had positive blood cultures with at least one resistant
      organism present and 36% had organisms resistant to multiple antibiotics. Fifty
      percent of patients with benign biliary disease and positive blood cultures had
      multiple organisms growing in their blood. Three-quarters of the isolates were
      resistant to one or more antibiotics and one-quarter of isolates were resistant
      to three or more antibiotics. Resistant organisms were found regardless of the
      cause of the biliary obstruction. DISCUSSION: For all causes of cholangitis,
      there is a high incidence of positive blood cultures and a high rate of
      antibiotic resistance. For optimal treatment, blood and/or bile cultures should
      be routinely performed to optimize antibiotic therapy.

PMID- 18333180
TI  - Laparoscopic choledochojejunostomy via PTFE-covered stent successfully achieves
      internal drainage of common bile duct obstruction.
AB  - The purpose of this study was to develop a method of laparoscopic biliary bypass
      utilizing a PTFE-covered biliary stent. An animal model of common bile duct
      obstruction was developed. Three days before the planned choledochojejunostomy,
      the common duct in 10 female pigs was ligated using mini-laparoscopy
      instrumentation (2 mm) to create an obstruction model. A laparoscopic
      choledochojejunostomy was then performed using intracorporal suturing (n=5) or
      stented (n=5) techniques. In the sutured group, a side-to-side two-layer
      anastomosis was performed. In the stented group, a Seldinger technique was used
      to deliver the stent into the abdomen through the small bowel and into the
      anterior wall of the common bile duct for deployment across both the duct and
      bowel to create an anastomosis (under fluoroscopic guidance). After the surgery,
      the animals were followed for 7 days, and then sacrificed to examine the
      anastomosis grossly and histologically. Statistical analysis was used to compare
      the two groups. Although the difference was not statistically significant, the
      mean anastomosis time in minutes was shorter for the stented group (37.8; range
      15-74 minutes) than in the sutured group (52.8; range 28-70 minutes). All animals
      survived for 7 days after the procedure with no detectable biliary leaks or
      biliary obstruction at autopsy. These gross findings were confirmed by pathologic
      examination of the anastomoses. Laparoscopic choledochojejunostomy using a PTFE
      covered metallic biliary stent can be performed to relieve common bile duct
      obstruction. In addition, the stent method was as safe and effective as sutured
      laparoscopic choledochojejunostomy.

PMID- 18333181
TI  - Ultrasonography in the diagnosis of true gallbladder polyps: the contradiction in
      the literature.
AB  - Polypoid lesions of the gallbladder (PLGs) are often incidentally identified
      during ultrasonographic examination of abdominal pain. The present study was
      designed to determine the reliability of ultrasonography (US) in the diagnosis of
      PLGs. The records of 853 patients who underwent laparoscopic cholecystectomy (LC)
      for PLGs in Gazi Medical School from January 2000 to January 2004 were reviewed.
      Data were collected regarding the patients' gender, age, symptoms, serum lipid
      levels, the size and the number of polyps on US, surgical indications for PLGs
      and histopathological diagnosis. In all, 56 of 853 patients had PLGs and
      underwent LC. Right upper quadrant pain (59%) was the most common presenting
      symptom that led to gallbladder US. Nearly 75% of the lesions were smaller than
      10 mm. At histopathologic examination cholesterolosis was found in 17 of 56 (30%)
      patients, and 12 of 56 (21%) demonstrated only cholelithiasis; 17 (30%) patients
      had both cholesterolosis and stones. Only 10 (18%) patients had adenomatous polyp
      and 8 of these polyps were larger than 1 cm. Overall US-based diagnosis of
      gallbladder polyp was inaccurate in 82%. The sensitivity and specificity of US
      for polyps <1 cm was 20% and 95.1%, respectively, whereas the sensitivity and
      specificity of US for polyps >1 cm was 80% and 99.3%, respectively. The accuracy
      of US in diagnosing PLGs was poor, especially in polyps <1 cm.

PMID- 18333182
TI  - Hepatic portal vein gas as a complication of cryotherapy.
AB  - BACKGROUND: Hepatic portal vein gas (HPVG) is a radiological finding normally
      associated with life-threatening conditions such as mesenteric ischaemia and
      necrotising enterocolitis in infants. Its presence has previously been associated
      with a high mortality rate. As a result of more sensitive imaging modalities the
      spectrum of conditions for which portal vein gas is detected has broadened. We
      present a patient who developed HPVG as a complication of cryotherapy. The
      association between portal vein gas and cryotherapy has not previously been
      described in well over one thousand patients with hepatic cryotherapy reported in
      the literature.

PMID- 18333184
TI  - Liver paper summary: IHPBA meeting 2004, Washington, DC.

PMID- 18333186
TI  - The role of the anesthesiologist as an integral member of the transplant team.

PMID- 18333185
TI  - Update of PET and PET/CT for hepatobiliary and pancreatic malignancies.

PMID- 18333187
TI  - Controversies in anesthetic management of liver transplantation.
AB  - Controversies in the anesthetic management of liver transplantation (OLT) include
      the exclusion of patients with pulmonary hypertension, intracranial pressure
      monitoring in patients with fulminant hepatic failure, preoperative screening for
      coronary artery disease, perioperative use of anticoagulant medications, and
      early extubation after surgery. This manuscript discusses these controversies
      from the perspective of two institutions that possess a long tradition of
      providing liver transplantations for patients with end-stage liver disease.

PMID- 18333189
TI  - Evidence-based medicine in HBP surgery: is there any?
AB  - BACKGROUND: Evidence-based medicine (EBM) has become widely accepted as a basis
      for clinical decision in many fields of medicine. This review examines the
      specific role of EBM in hepato-biliary and pancreatic (HBP) surgery. EBM relies
      on four main sources, including clinical guidelines, meta-analyses, primary
      information and clinical experience. Randomized controlled trials (RCTs)
      constitute the cornerstone of EBM and a recent study reported that there are
      relatively few RCTs evaluating the effectiveness of surgical therapies and
      procedures (1,530 out of 45,342 or 3.4% in five leading surgical journals) and
      only a few in HBP surgery. Although the effort must be to implement EBM as far as
      possible in HBP surgery, there are several obstacles to conducting RCTs in HBP
      surgery, including problems associated with standardization of surgical skills,
      sham-operations often impossible to perform, and the general applicability of
      specific findings may be uncertain. DISCUSSION: This paper will provide two
      relevant examples of EBM in HBP surgery in patients with hepatic metastases and
      pancreatic adenocarcinoma, illustrating some problems but also the potential of
      introducing EBM in HBP surgery. In the future, our effort must be devoted to
      implementing EBM in applicable areas of HBP surgery but also remembering that in
      certain areas accumulated knowledge from observational studies, including
      drainage of abscesses and surgical treatment of intestinal obstruction, may have
      similar or even higher clinical value than RCTs.

PMID- 18333188
TI  - Liver cell adenoma and liver cell adenomatosis.
AB  - During the last three decades liver cell adenoma and liver cell adenomatosis have
      emerged as new clinical entities in hepato-logical practice due to the widespread
      use of oral contraceptives and increased imaging of the liver. On review of
      published series there is evidence that 10% of liver cell adenomas progress to
      hepatocellular carcinoma, diagnosis is best made by open or laparoscopic excision
      biopsy, and the preferred treatment modality is resection of the liver cell
      adenoma to prevent bleeding and malignant transformation. In liver cell
      adenomatosis, the association with oral contraceptive use is not as high as in
      solitary liver cell adenomas. The risk of malignant transformation is not
      increased compared with solitary liver cell adenomas. Treatment consists of close
      monitoring and imaging, resection of superficially located, large (>4 cm) or
      growing liver cell adenomas. Liver transplantation is the last resort in case of
      substantive concern about malignant transformation or for large, painful adenomas
      in liver cell adenomatosis after treatment attempts by liver resection.

PMID- 18333190
TI  - Intra-operative acute isovolemic hemodilution is safe and effective in
      eliminating allogeneic blood transfusions during right hepatic lobectomy:
      comparison of living donor versus non-donors.
AB  - BACKGROUND: Multiple studies have shown acute isovolemic hemodilution (AIH) to be
      safe and effective during liver resection to limit the use of banked blood.
      However, no studies to date have studied AIH in living donor right hepatectomy.
      Conventional right hepatectomies for living donors is not identical to non-donor
      right hepatectomies. Since division of the parenchyma is often performed without
      devascularization of the right lobe, blood loss may be significantly higher.
      METHODS: Ten consecutive patients undergoing living donor right hepatectomies
      (LDRH) and ten consecutive patients undergoing non-donor right hepatectomies
      (NDRH) were compared using AIH. RESULTS: There was no mortality or morbidity
      related to the use of AIH. No allogeneic blood transfusions were required in
      either group, intra-operatively or post-operatively. There was no significant
      difference in post-operative hematocrit, average estimated blood loss, and
      average fluid replacement. Average hospital length of stay and operating room
      time were longer for the LDRH. CONCLUSION: AIH can be performed safely and
      effectively in both LDRH and NDRH without subjecting patients to unnecessary
      risks of allogeneic blood transfusions.

PMID- 18333191
TI  - Diagnostic laparoscopy in the evaluation of the viral hepatitis patient with
      potentially resectable hepatocellular carcinoma.
AB  - BACKGROUND: Despite significant recent improvements in liver imaging,
      preoperative evaluation of the potentially resectable patient with viral
      Hepatitis and Hepatocellular Carcinoma (HCC) is often inaccurate. Diagnostic
      laparoscopy may change management for patients with under-appreciated nodular
      cirrhosis or intrahepatic metastases, preventing unnecessary open exploration.
      The purpose of this study is to determine the effectiveness of routine
      laparoscopy as a separate procedure prior to resection in the evaluation of
      patients with potentially resectable HCC. METHODS: Patients with potentially
      resectable HCC were evaluated preoperatively with routine blood tests and axial
      imaging. All study patients also underwent diagnostic laparoscopy with
      laparoscopic ultrasonography. Laparoscopy was performed in an inpatient hospital
      setting, with 23 hour stays in most cases. RESULTS: Among 65 patients evaluated
      with Hepatocellular Carcinoma between July 2001 and November 2003, 20 patients
      with potentially resectable disease were evaluated by diagnostic laparoscopy. All
      patients had viral Hepatitis: 16 with Hepatitis B and 4 with Hepatitis C. All
      study patients had cirrhosis; 18 classified as Child's-Pugh A and 2 as Child's
      Pugh B. Diagnostic laparoscopy changed the management in 9/20 (45%) cases.
      Management was changed because of severe nodular cirrhosis in 4 cases, inaccurate
      assessment of intrahepatic metastases in 2 cases, inability to identify an HCC in
      1 case, peritoneal carcinomatosis in 1 case, and inability to tolerate induction
      to general anesthesia in 1 case. DISCUSSION: Diagnostic laparoscopy is useful in
      the evaluation of the potentially resectable patient with HCC. Information
      obtained from laparoscopy may change the clinical management in up to 45% of
      cases.

PMID- 18333192
TI  - Hepatic resection in 170 patients using saline-cooled radiofrequency coagulation.
AB  - BACKGROUND: Hepatic resection for malignancies or symptomatic benign liver
      lesions remains the standard of treatment. Historically, the principal cause of
      mortality during liver resection was intraoperative bleeding. Advances in
      surgical and anesthetic techniques, along with application of new technologies,
      have decreased blood loss and dramatically improved the outcomes for major liver
      surgery. METHODS: The purpose of this prospective study was to determine the
      utility of a saline-cooled radiofrequency coagulation device (TissueLink Medical,
      Inc.) for hepatic resection. Intraoperative bleeding, blood transfusion,
      postoperative bile leak, and other complications were noted. RESULTS: The results
      are described for 170 patients undergoing hepatic resection over a three-year
      period. There were no intraoperative or postoperative deaths. Six patients in the
      series received blood transfusions for a transfusion rate of 3.5%. Four patients
      experienced a transient postoperative bile leak. Three of the four closed
      spontaneously prior to discharge home, and the fourth closed promptly after ERCP.
      There were no episodes of postoperative hemorrhage, hepatic failure, liver
      abscess, or reoperation. CONCLUSIONS: The saline-cooled radiofrequency
      coagulation device is very effective in achieving intraoperative hemostasis and
      facilitates liver parenchymal transection during hepatic resection.

PMID- 18333193
TI  - Radiofrequency ablation versus surgical resection for single nodule
      hepatocellular carcinoma: long-term outcomes.
AB  - BACKGROUND: Radiofrequency ablation (RFA) has been increasingly utilized for
      treatment of hepatocellular carcinoma (HCC). Long-term results of RFA, especially
      in comparison to surgical resection, have not been well described. METHODS:
      Eighty-seven patients with single nodule HCC underwent surgical resection (N=47)
      or RFA (N=40) during a 9-year period. RFA was performed for 36 unresectable
      disease and 4 surgical refusals. Each group was further divided based on tumor
      size for analysis; Group 1: resection, <or=5 cm (N=18), Group 2: RFA, <or=5 cm
      (N=26), Group 3: resection, >5 cm (N=29) and Group 4: RFA, >5 cm (N=14). Follow
      up ranged from 2 to 72 months (median 16 months). Patients' characteristics,
      local recurrences and overall and disease-free survivals were compared. RESULTS:
      Patients who underwent RFA were older (69 versus 60, p=0.0006), had more advanced
      Child-Pugh class and TNM stage (p=0.0002 and p=0.016, respectively), and had
      smaller tumors (4.6 versus 7.4 cm, p=0.0032). Local recurrence rates were 2% for
      resection and 10% for RFA (p=0.12). These local and other recurrences were
      subsequently treated with multimodal therapies as indicated. The median overall
      and disease-free survivals were equivalent both between Groups 1 and 2 (49 versus
      51 months, p=0.44, 36 versus 22 months, p=0.84), and Groups 3 and 4 (47 versus
      463 months, p=0.94, 28 versus 20 months, p=0.67). DISCUSSION: Although the groups
      were not truly comparable, this retrospective study suggests that RFA may offer
      similar long-term results to surgical resection for single nodule HCC when
      combined with multimodal treatments.

PMID- 18333194
TI  - Anatomic segmental resection compared to major hepatectomy in the treatment of
      liver neoplasms.
AB  - BACKGROUND: Familiarity with liver anatomy and refinements in operative technique
      have led to interest in liver conservation when dealing with hepatic tumors.
      There is thought to be less morbidity, less blood loss (EBL), a shorter hospital
      stay (LOS), and no penalty for long-term survival with segmental hepatectomy.
      METHODS: One hundred ninety-six patients who underwent segmental (SEG group)
      (N=70) or major (MAJOR group) (N=126) hepatectomy for liver neoplasms were
      retrospectively reviewed. Clinical parameters of mortality, morbidity, EBL, LOS,
      and actuarial survival in patients with colorectal metastases were examined.
      RESULTS: There were no differences in age or gender between the SEG and MAJOR
      groups. There were no deaths among 64 non-cirrhotic patients in the SEG group and
      4 deaths (3.2%) among 124 non-cirrhotic patients in the MAJOR group (p=0.19).
      There were 4 postoperative complications in the SEG group (5.6%) and 22 in the
      MAJOR group (17.3%) (p<0.05).The EBL for the SEG group was 912+/-842 ml compared
      to 3675+/-3110 ml in the MAJOR group (p<0.001).The hospital LOS for the SEG group
      was 9.4+/-6.4 days and for the MAJOR group 10.2+/-5.9 days (p=0.32). Life table
      analysis of survival for resection of colorectal metastases showed two-year
      patient survival of 40% in the SEG group (N=17) and 45% for the MAJOR group
      (N=46). CONCLUSION: Segmental resections were associated with less EBL and fewer
      postoperative complications. There was a trend towards fewer deaths in non
      cirrhotic patients, and no apparent penalty for a smaller hepatic resection in
      long-term survival. While sometimes technically more challenging, segmental
      resections are preferable when feasible and should be utilized in efforts to
      conserve liver parenchyma.

PMID- 18333195
TI  - Factors affecting outcome in liver resection.
AB  - BACKGROUND: Studies demonstrate an inverse relationship between
      institution/surgeon procedural volumes and patient outcomes. Similar studies
      exist for liver resections, which recommend referral of patients for liver
      resections to 'high-volume' centers. These studies did not elucidate the factors
      that underlie such outcomes. We believe there exists a complex interaction of
      patient-related and perioperative factors that determine patient outcomes after
      liver resection. We sought to delineate these factors. METHODS: Retrospective
      review of 114 liver resections by a single surgeon from 1993-2003: Records were
      reviewed for demographics; diagnosis; type/year of surgery; American Society of
      Anesthesiologists (ASA) score; preoperative albumin, creatinine, and bilirubin;
      operative time; intraoperative blood transfusions; epidural use; and
      intraoperative hypotension. Main outcome measurements were postoperative
      morbidities, mortalities and length of stay (LOS). Data were analyzed using a
      multivariate linear regression model (SPSS v10.1 statistical analysis program).
      RESULTS: Primary indications for resections were hepatocellular carcinoma (HCC)
      (N=57), metastatic colorectal cancer (N=25), and benign disease (N=18). There
      were no intraoperative mortalities and 4 perioperative (30-day) mortalities
      (3.5%). Mortality occurred in patients with malignancies who were older than 50
      years. Morbidity was higher in malignant (15.6%) versus benign (5.5%) disease.
      Complications included bile leak/stricture (N=6), liver insufficiency (N=3),
      postoperative bleeding (N=2), myocardial infarction (N=2), aspiration pneumonia
      (N=1), renal insufficiency (N=1), and cancer implantation into the wound (N=1).
      Average LOS for all resections was 8.6 days. Longer operative time (p=0.04),
      lower albumin (p<0.001), higher ASA score (p<0.001), no epidural use (p=0.04),
      and higher creatinine (p<0.001) all correlated positively with longer LOS. ASA
      score and creatinine were the strongest predictors of LOS. LOS was not affected
      by patient age, sex, diagnosis, presence of malignancy, intraoperative
      transfusion requirements, intraoperative hypotension, preoperative bilirubin,
      case volume per year or year of surgery. CONCLUSIONS: Liver resections can be
      performed with low mortality/morbidity and with acceptable LOS by an experienced
      liver surgeon. Outcome as measured by LOS is most influenced by patient
      comorbidities entering into surgery. Annual case volume did not influence LOS and
      had no impact on patient safety. Length of stay may not reflect
      surgeon/institution performance, as LOS is multifactorial and likely related to
      patient population, patient selection and increased high-risk cases with a
      surgeon's experience.

PMID- 18333196
TI  - The role of omentoplasty in the surgical management of remnant cavity in hepatic
      hydatid cyst.
AB  - BACKGROUND: Cyst hydatid disease of the liver is still endemic in certain regions
      of the world. Currently, surgical operation remains the treatment of choice in
      hydatidosis. The cyst cavity can be managed by using capitonnage, external
      drainage, introflexion or omentoplasty. METHODS: Two hundred and thirty-five
      patients operated for hydatid cyst between January 1990 and February 2001 were
      analysed retrospectively. Either omentoplasty, external drainage, capitonnage or
      introflexion were used to treat residual cyst cavity. RESULTS: Patients were
      categorised into three groups to evaluate complications: omentoplasty alone
      (group A), omentoplasty combined with other techniques (group B) and other
      techniques (group C). The overall mortality rates were <1%. Overall morbidity
      rates were 8.8% for group A, 19% for group B and 25% for group C, respectively.
      Mean hospital stay was 7.6 days for group A, 11.9 days for group B and 15.8 days
      for group C. DISCUSSION: Postoperative surgical site infection, bile fistula,
      recurrence rate and overall morbidity were seen less frequently in patients who
      underwent omentoplasty in our series. Mean duration of hospital stay was
      significantly shorter in patients who underwent omentoplasty operations. Because
      omentum has a high absorptive capacity and the capability to fill the residual
      cavity, we recommend omentoplasty to manage patients with hydatid cyst of the
      liver, whether complicated or uncomplicated.

PMID- 18333197
TI  - Influence of pre-operative diagnosis and frozen section on operative management
      of pancreatic cystic lesions.
AB  - BACKGROUND: Frozen section analysis of cyst wall has been advocated as standard
      of care prior to surgical drainage of pancreatic pseudocysts. Recent studies have
      indicated that frozen section may be unreliable. Our aim was to investigate the
      role and accuracy of frozen section analysis of the cyst wall in the operative
      management of pancreatic cystic lesions. METHODS: A retrospective review was
      performed of 44 patients who underwent operation for a cystic lesion of the
      pancreas. RESULTS: Of the 25 patients with a diagnosis of pseudocyst, 9 patients
      had frozen section intra-operatively. Eight frozen sections demonstrated
      pseudocyst, and correlated with final pathology. One frozen section demonstrated
      a true cyst. Twenty-three patients had a final diagnosis of pseudocyst. Nineteen
      patients had a diagnosis of cystic neoplasm, and six patients had frozen
      sections. Three frozen sections were consistent with cystic neoplasm and
      correlated with final pathology. Three frozen sections demonstrated
      characteristics of pseudocyst, two correlated with final pathology, and one
      showed cystic neoplasm on final pathology. CONCLUSION: Routine use of frozen
      section may not be necessary; however, frozen section is useful when the intra
      operative appearance does not correlate with pre-operative diagnosis.

PMID- 18333199
TI  - Symposium on hilar cholangiocarcinoma.

PMID- 18333200
TI  - Hilar cholangiocarcinoma: diagnosis and staging.
AB  - Cancer arising from the proximal biliary tree, or hilar cholangiocarcinoma,
      remains a difficult clinical problem. Significant experience with these uncommon
      tumors has been limited to a small number of centers, which has greatly hindered
      progress. Complete resection of hilar cholangiocarcinoma is the most effective
      and only potentially curative therapy, and it now clear that concomitant hepatic
      resection is required in most cases. Simply stated, long-term survival is
      generally possible only with an en bloc resection of the liver with the
      extrahepatic biliary apparatus, leaving behind a well perfused liver remnant with
      adequate biliary-enteric drainage. Preoperative imaging studies should aim to
      assess this possibility and must evaluate a number of tumor-related factors that
      influence resectability. Advances in imaging technology have improved patient
      selection, but a large proportion of patients are found to have unresectable
      disease only at the time of exploration. Staging laparoscopy and (13)fluoro
      deoxyglucose positron emission tomography (FDG-PET) may help to identify some
      patients with advanced disease; however, local tumor extent, an equally critical
      determinant of resectability, may be underestimated on preoperative studies. This
      paper reviews issues pertaining to diagnosis and preoperative evaluation of
      patients with hilar biliary obstruction. Knowledge of the imaging features of
      hilar tumors, particularly as they pertain to resectability, is of obvious
      importance for clinicians managing these patients.

PMID- 18333201
TI  - Preoperative optimization of the liver for resection in patients with hilar
      cholangiocarcinoma.
AB  - Optimal preoperative preparation is required to reduce operative risk of major
      hepatectomy in jaundiced patients. The role of percutaneous preoperative biliary
      drainage (PTBD) is, apart from assessment of intraductal extent of the tumour, to
      allow contralateral hypertrophy if portal vein embolization (PVE) is performed.
      The increased use of PTBD over a 10-year period was associated with increased
      resectability rate in this study, while PTBD-related complications decreased.
      Efficient hypertrophy of the future liver remnant (FLR) requires biliary drainage
      to reduce the risk of postoperative liver dysfunction. Preoperative staging
      laparoscopy avoided unnecessary surgical exploration in 20% of patients
      previously considered resectable.

PMID- 18333202
TI  - Operative considerations in resection of hilar cholangiocarcinoma.
AB  - This article reviews the preoperative evaluation and operative considerations in
      patients with hilar cholangiocarcinoma. The preoperative evaluation is based on
      the imaging evaluation of the longitudinal and radial extent of the tumour along
      and around the hepatic duct confluence. The use of portal vein embolization to
      increase the safety of extended hepatectomy and the extent of surgical resection
      (caudate lobe and portal vein) are discussed within the context of recently
      published series.

PMID- 18333203
TI  - Surgical management of hilar cholangiocarcinoma: the Nagoya experience.
AB  - Of 400 patients with hilar cholangiocarcinoma who were treated at Nagoya
      University Hospital from 1977 to 2004, 301 (75%) underwent surgical resection.
      Most patients underwent major hepatectomy with extrahepatic bile duct resection.
      The overall mortality rate was 7.6% but had decreased to 2.5% in the last 5 years
      (p=0.007). The overall survival rates at 5, 10 and 15 years were 22%, 13% and
      10%, respectively. The survival rates of 233 patients undergoing R0 resection
      were 27%, 16% and 13%, respectively. R1 or R2 resection, lymph node metastasis
      and portal vein involvement were significant negative prognostic factors,
      although survival was better than in patients with unresected tumours. The
      results show that aggressive surgical treatment of hilar cholangiocarcinoma
      offers good outcomes with an acceptable mortality rate.

PMID- 18333204
TI  - The importance of complete excision of the caudate lobe in resection of hilar
      cholangiocarcinoma.
AB  - BACKGROUND: The numbers of margin-negative resections and survival times have
      greatly improved because of a more aggressive surgical approach to resectable
      hilar cholangiocarcinoma (Klatskin tumour). It was shown initially by Japanese
      authors that complete resection of the caudate lobe together with partial
      hepatectomy leads to more margin-negative resections. However, this concept has
      not been unanimously taken up by Western authors. The aim of this study was to
      examine the role of complete caudate lobe resection in our series of resected
      hilar cholangiocarcinomas. METHODS: Between January 1993 and January 2003, 54
      patients underwent resection for Klatskin tumours. These patients were divided
      into two groups, according to the two 5-year periods in which they had been
      operated. In the first period, patients did not routinely undergo complete
      excision of the caudate lobe, whereas in the second period, partial liver
      resection was combined with complete excision of the caudate lobe in 15 patients.
      These two patient groups were evaluated with respect to postoperative morbidity
      and mortality, microscopic tumour margins and survival time. RESULTS:
      Postoperative complications occurred in 59% of patients in total, while overall
      mortality was 11%. No difference was found in postoperative morbidity or
      mortality between the two periods. A significantly higher number of margin
      negative resections was found in the second 5-year period, together with improved
      survival. CONCLUSION: Concomitant complete excision of segment 1 for patients
      with hilar cholangiocarcinoma did not lead to increased morbidity or mortality.
      Therefore the addition of complete excision of segment 1 is a safe procedure
      contributing to a higher rate of R0 resections and improved survival.

PMID- 18333205
TI  - The role of liver transplantation in the treatment of hilar cholangiocarcinoma.
AB  - Surgical resection or liver transplantation (LTx) are the only available
      treatments that offer a potential for long-term survival or cure in cases of
      hilar cholangiocarcinoma. Hilar resection in combination with partial hepatectomy
      and caudate lobectomy is regarded as the current treatment of choice. Overall 5
      year survival rates range from 9% to 28%, and reach as high as 24-43% in R0
      resections. Five-year survival rates in the very limited experience with LTx in
      hilar cholangiocarcinoma are not dramatically worse than those after resection.
      However, hilar cholangiocarcinoma is not at present an accepted indication for
      LTx given both the good results of LTx for benign diseases and the dramatic organ
      shortage. When compared with the prognosis of other gastrointestinal tumours,
      these survival rates are encouraging in the setting of an otherwise unresectable
      malignancy. As such, and considering the fact that it may represent the only
      possibility for cure, the general exclusion of patients with cholangiocarcinomas
      as candidates for LTx does not seem to be justified. Furthermore, recent advances
      in multimodal tumour therapy seem to be most promising in combination with LTx.
      Prospective studies are required to elucidate the influence of better patient
      selection and the role of multimodal treatments on the outcome of LTx in hilar
      cholangiocarcinoma. If the encouraging data achieved with neoadjuvant therapy
      prior to LTx are confirmed by further studies, we foresee that renewed interest
      in LTx for hilar cholangiocarcinoma could arise.

PMID- 18333206
TI  - Surgical palliation for unresectable hilar cholangiocarcinoma.
AB  - The majority of patients who present with hilar cholangiocarcinoma will have
      incurable disease and require only palliation. Efficient relief of disabling
      symptoms is required with minimal morbidity and mortality and can be achieved by
      either surgical or non-operative options. A review of the indications, anatomical
      considerations and surgical techniques is presented. Segment III cholangio
      jejunostomy is the most frequently used surgical bypass procedure and in those
      patients with an expected survival of more than 6 months, surgical palliation
      offers good quality and long-lasting palliation. There is a need for randomized
      controlled data to define the optimal role of surgical palliation in this
      difficult disease.

PMID- 18333207
TI  - Radiation therapy, chemotherapy and chemoradiation in hilar cholangiocarcinoma.
AB  - BACKGROUND: Hilar cholangiocarcinoma is a rare tumour which is best managed by an
      aggressive surgical approach. The role of adjuvant or neoadjuvant radiation
      therapy, chemotherapy or chemoradiation remains controversial, as no prospective
      randomized studies have been performed. METHODS: This review summarizes the
      recent literature regarding the role of radiation, chemotherapy and
      chemoradiation in hilar cholangiocarcinoma. The results of a biliary cancer
      questionnaire regarding current treatment strategies are also reported. RESULTS:
      A number of retrospective studies have shown that patients treated with adjuvant
      radiation therapy have prolonged survival compared with untreated patients.
      However, most of these reports did not control for tumour stage or performance
      status. A carefully controlled trial from the Johns Hopkins Hospital did not
      demonstrate any benefit for adjuvant radiation therapy. A number of phase II
      trials of chemotherapy have demonstrated modest response rates (20-40%). The best
      responses have been reported with 5-fluorouracil (5-FU) in combination with
      interferon-alpha or with leucovorin and mitomycin C. Recent non-randomized
      reports of chemoradiation with 5-FU with or without gemcitabine as the
      radiosensitizer suggest, but do not prove, improved survival. Adjuvant
      chemoradiation is currently being employed at specialized centres most often in
      the Americas (71%) and the Asia/Pacific region (55%) and to a lesser degree in
      Europe (29%). DISCUSSION: The only chance for long-term survival in patients with
      hilar cholangiocarcinoma is complete resection with negative margins. Neither
      radiation therapy nor chemotherapy alone has been proven to prolong survival in
      completely or partially resected patients or in unresected patients. Recent
      uncontrolled data suggest that chemoradiation may improve survival in resected
      and locally unresectable patients. However, prospective, randomized multicentre
      trials need to be performed to confirm efficacy.

PMID- 18333208
TI  - Idiopathic benign biliary strictures in surgically resected patients with
      presumed cholangiocarcinoma.
AB  - OBJECTIVE: Distinguishing between malignant and benign biliary strictures remains
      problematic. The aim of this study was to compare and contrast the clinical
      features of patients with benign and malignant biliary strictures. METHODS:
      Medical records of patients who underwent surgical resection for presumed
      cholangiocarcinoma were reviewed. Immunohistochemistry for hypoxia inducible
      factor-1-alpha (HIF-1-alpha) was performed on all bile ductule samples. RESULTS:
      Twelve patients with benign strictures (group I) were compared to 26 patients
      with cholangiocarcinoma (group II). Group I was predominantly female (ratio 2:
      1), (p<0.01), whereas the gender ratio was 1: 1 in patients in group II. Bismuth
      Corlette type strictures in group I were more likely to be type I/II, whereas
      type III strictures predominated in group II. The CA 19-9 was <100 U/ml in 6 and
      >100 U/ml in 1 patient of group I and <100 in 13 and >100 in 11 patients in group
      II. Half of the patients in group I had positive immunoreactivity for HIF-1-alpha
      in bile ductules. CONCLUSION: Benign biliary strictures masquerading as
      cholangiocarcinomas occur more often in women, are less often Bismuth-Corlette
      type III, have serum CA 19-9 values <100 U/ml, and hypoxia may play a role in a
      subset of these strictures.

PMID- 18333209
TI  - A matrix metalloproteinase inhibitor to treat unresectable cholangiocarcinoma.
AB  - Matrix metalloproteinases (MMPs) are implicated in tumour invasion and
      metastasis. We report the first use of an MMP inhibitor to treat unresectable
      cholangiocarcinoma. Four men with stage IV cholangiocarcinoma received oral
      Marimastat (10 mg bd) indefinitely following relief of obstructive jaundice.
      Monthly measurements of the tumour marker CA 19-9 were used as an indicator of
      disease response and activity. CA 19-9 levels dropped sharply and stayed low in
      the two patients who appeared to respond. Mean survival of the four patients was
      21.5 months (range 4-48 months). Side effects were well tolerated. A more
      extensive and detailed examination of MMP inhibitors to treat cholangiocarcinoma
      is indicated.

PMID- 18333210
TI  - Indications for non-transplant surgery in primary sclerosing cholangitis.
AB  - Primary sclerosing cholangitis (PCS) is a progressive disease leading to
      secondary biliary cirrhosis. Patients are at increased risk of developing
      cholangiocarcinoma, which is usually diagnosed at an advanced stage. Treatment of
      PCS includes medical therapy, endoscopic biliary dilation, percutaneous
      transhepatic stenting, extrahepatic biliary resection and liver transplantation.
      The most effective management of primary sclerosing cholangitis before the onset
      of cirrhosis remains unclear. Non-transplant surgical procedures have a limited
      but defined role in patients with PCS. Resection of the extrahepatic biliary tree
      in symptomatic non-cirrhotic patients improves hyperbilirubinaemia and prolongs
      both transplant-free and overall survival when compared with non-operative
      dilation and/or stenting. Surgical resection may also definitively establish or
      exclude a diagnosis of cholangiocarcinoma in patients with dominant extrahepatic
      or perihilar strictures. Extrahepatic bile duct resection may also reduce the
      risk of cholangiocarcinoma. Extrahepatic biliary resection should be considered
      in selected non-cirrhotic patients with symptomatic biliary obstruction and
      dominant extrahepatic and/or perihilar strictures. Those patients in whom
      cholangiocarcinoma is suspected should also undergo resection.

PMID- 18333211
TI  - Focal nodular hyperplasia: what are the indications for resection?
AB  - Focal nodular hyperplasia (FNH) is a benign condition of the liver that is often
      discovered incidentally on radiological investigation. FNH has no malignant
      potential, is rarely symptomatic and surgical intervention is almost never
      required. However, eight patients with a diagnosis of FNH associated with upper
      abdominal pain or rapid growth were referred for surgery. All patients had been
      extensively investigated for other causes of pain and had been observed for
      between 1 and 7 years prior to surgical referral. The FNH lesions were between 1
      cm and 8 cm in diameter. One FNH lesion 7.5 cm in diameter lay in segment
      VII/VIII and was related to the right and middle hepatic veins. All patients were
      resected with immediate and lasting control of their symptoms. Based on this
      experience FNH should be managed in a manner similar to haemangiomas with most
      lesions being safe to observe. However, it should be recognized that symptomatic
      FNH does occur, as well as FNH behaving in an unusual fashion such as rapid
      growth. Both of these findings are indications for resection.

PMID- 18333212
TI  - Electrical activation of common bile duct nerves modulates sphincter of Oddi
      motility in the Australian possum.
AB  - BACKGROUND: Sphincter of Oddi (SO) motility is regulated by extrinsic and
      intrinsic nerves. The existence of neural circuits between the SO and the
      proximal extrahepatic biliary tree has been reported, but they are poorly
      understood. Using electrical field stimulation (EFS), we determined if a neural
      circuit exists between the common bile duct (CBD) and the SO in anaesthetized
      Australian brush-tailed possums. METHODS: The gallbladder, cystic duct or CBD
      were subjected to EFS with a stimulating electrode. Spontaneous SO phasic waves
      were measured by manometry. RESULTS: EFS at sites on the distal CBD (12-20 mm
      proximal to the SO), but less commonly at more proximal CBD, evoked a variety of
      responses consisting of an excitatory and/or inhibitory phase. Bi-phasic
      responses consisting of an excitation followed by inhibition were the most
      common. Tri-phasic responses were also observed as well as excitation or
      inhibition only. These evoked responses were blocked by topical application of
      local anaesthetic to the distal CBD or transection of the CBD. EFS at sites on
      the gallbladder body, neck or cystic duct did not consistently evoke an SO
      response. Pretreatment with atropine or guanethidine reduced the magnitude of the
      evoked response by about 50% (p<0.05), pretreatment with hexamethonium had no
      consistent effect and pretreatment with a nitric oxide synthase inhibitor
      increased the response. DISCUSSION: A neural circuit(s) between the SO and the
      distal CBD modulates SO motility. Damage to this area of the CBD during bile duct
      exploration surgery could adversely affect SO motility.

PMID- 18333213
TI  - The current status of hepatobiliary and pancreatic surgical literature.
AB  - BACKGROUND: A rapidly growing knowledge base has evolved describing recently
      developed diagnostic and therapeutic techniques in the management of hepatic
      pancreatic-biliary (HPB) disease. As such, it is expected that the current
      literature should reflect these trends in the emerging specialty of HPB surgery.
      METHODS: The content of 10 leading surgical journals was assessed for the
      separate years 1998 and 2002 using a combination of hand searching and Medline
      searching using the Pubmed search engine. Data retrieved for each journal
      included: total number/type of publication, specialty category, disease focus and
      comment on surgical technique. RESULTS: A total of 817 HPB articles were reviewed
      (386 in 1998,431 in 2002). Half of the journals showed an absolute increase in
      the number of HPB articles published; the largest increase was for Surgery (12%;
      2002: 64/431; 1998: 10/386, p<0.0001), while the British Journal of Surgery
      displayed the greatest decrease (11%; 2002: 56/431; 1998: 94/386, p<0.0001).
      Publication by the nature of disease revealed that overall, there was a trend
      towards a greater volume of publications on malignant disease over the 4-year
      period (1998: 41%; 2002: 56%). Furthermore, 91% (10/11) of articles published by
      the Canadian Journal of Surgery related to benign disease; while almost all (97%)
      of the articles published by the Annals of Surgical Oncology were on malignant
      disease. There was a difference in the pathology focus for each sub-category of
      HPB topics. Fifty percent (150/302) of the articles on hepatic disease focused on
      malignancy, as compared with 46% (124/272) of those on pancreatic disease and 21%
      (44/213) of those on biliary disease. A comment on surgical technique was uniform
      across all categories (47% hepatic, 48% pancreatic and 44% biliary). DISCUSSION:
      Articles dealing with HPB topics are published widely across all reviewed
      journals. Although the absolute number of HPB articles published increased over a
      4-year period, there is significant variability in overall topics and focus of
      publication between journals. Overall, there was a uniform paucity of basic
      science articles, evidence-based reviews and/or meta-analyses, indicating an
      opportunity for growth in the future.

PMID- 18333214
TI  - Acute upper gastrointestinal haemorrhage resulting in transient hepatic failure
      following liver resection.
AB  - BACKGROUND: Both acute stress ulcer and liver failure are well-known
      complications of hepatic resection. This case study documents how an episode of
      postoperative gastrointestinal haemorrhage can provoke transient hepatic failure.
      CASE OUTLINE: A 66-year-old woman with no previous history of reflux oesophagitis
      or peptic ulcer disease underwent a right liver resection for a solitary
      metastasis. On the fifth postoperative day, with a small premonitory
      haematemesis, she was started on omeprazole intravenously. She subsequently
      required blood transfusion and endoscopy; a bleeding acute gastric ulcer was
      injected with adrenalin. She then progressed to acute liver failure with
      associated hepatic encephalopathy but made a full recovery. DISCUSSION: Adverse
      effects of prophylactic H(2) receptor antagonists have included liver failure and
      hepatitis, and animal studies have shown inhibition of liver regeneration after
      hepatectomy. Proton pump inhibitors (PPIs) have an acceptable profile of adverse
      events and their effect on liver regeneration appears to be favourable. Given the
      serious potential for liver failure in the event of significant bleeding, a PPI
      is advocated for routine prophylaxis against acute stress ulceration in all major
      liver resections.

PMID- 18333215
TI  - Haemobilia 2 weeks after a low thoracic stab wound.
AB  - BACKGROUND: Haemobilia occurs in only 1.2-5% of patients with accidental liver
      trauma. We describe an unusual case 2 weeks after penetrating thoracic injury.
      CASE OUTLINE: A 27-year-old man underwent laparotomy for hepatic bleeding after a
      low thoracic stab wound. Two weeks later rectal blood loss occurred. CT scan and
      angiography revealed intrahepatic contrast extravasation at the previous stab
      wound site. Coils were successfully placed into two branches of the right hepatic
      artery. DISCUSSION: Haemobilia should be considered in patients presenting with
      gastrointestinal blood loss after liver injury. It is diagnosed with angiography
      and preferably treated by embolisation.

PMID- 18333217
TI  - Current techniques of liver transection.
AB  - The operative mortality rate of liver resection has decreased from 10% to 20%
      before the 1980s to <5% in most specialized hepatobiliary centers nowadays. The
      most important factor for better outcome is reduced blood loss due to improvement
      in surgical techniques. Liver transection is the most challenging part of liver
      resection, associated with a risk of massive hemorrhage. Understanding the
      segmental anatomy of the liver and delineation of the proper transection plane
      using intraoperative ultrasound are prerequisites to safe liver transection.
      Clamp crushing and ultrasonic dissection are the two most widely used transection
      techniques. In recent years, new instruments using different types of energy for
      coagulation or sealing of vessels have been developed for liver transection.
      These include radiofrequency devices, Harmonic Scalpel, Ligasure and TissueLink
      dissecting sealer. Whether these new instruments, used alone or in combination
      with clamp crushing or ultrasonic dissection, improve the safety of liver
      transection has not been clearly demonstrated. The use of the vascular stapler
      for transection of major intrahepatic vascular trunks is also gaining popularity.
      These new instruments are particularly useful in liver transection during
      laparoscopic liver resection. Adjunctive measures such as intermittent Pringle
      maneuver and low central venous pressure anesthesia are also useful measures to
      reduce the risk of hemorrhage. This article reviews the safety and efficacy of
      different techniques of liver transection, with particular attention to evidence
      from randomized controlled trials available in the literature.

PMID- 18333219
TI  - Prospective randomized study of the benefits of preoperative corticosteroid
      administration on hepatic ischemia-reperfusion injury and cytokine response in
      patients undergoing hepatic resection.
AB  - BACKGROUND: Hepatic injury secondary to warm ischemia and reperfusion (I/R)
      remains an important clinical issue following liver surgery. The aim of this
      prospective, randomized study was to determine whether steroid administration may
      reduce liver injury and improve short-term outcome. PATIENTS AND METHODS: Forty
      three patients undergoing liver resection were randomized to a steroid group or a
      control group. Patients in the steroid group received 500 mg of
      methylprednisolone preoperatively. Serum levels of alanine aminotransferase
      (ALT), aspartate aminotransferase (AST), total bilirubin, anti-thrombin III (AT
      III), prothrombin time (PT), interleukin-6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha) were compared between the two groups. Length of stay and type
      and number of complications were recorded. RESULTS: Postoperative serum levels of
      ALT, AST, total bilirubin, and inflammatory cytokines were significantly lower in
      the steroid group than in controls. The postoperative level of AT-III in the
      control group was significantly lower than in the steroid group (ANOVA p < 0.01).
      The incidence of postoperative complications in the control group tended to be
      significantly higher than that in the steroid group. CONCLUSION: These results
      suggest that steroid pretreatment represents a potentially important biologic
      modifier of I/R injury and may contribute to maintenance of
      coagulant/anticoagulant homeostasis.

PMID- 18333220
TI  - Evaluation of an online navigation system for laparoscopic interventions in a
      perfused ex vivo artificial tumor model of the liver.
AB  - BACKGROUND: Laparoscopic radiofrequency ablation (RFA) is a safe and effective
      method for tumor destruction in patients with unresectable liver tumors. However,
      accurate probe placement using laparoscopic ultrasound guidance is required to
      achieve complete tumor ablation. After evaluation of an ultrasound navigation
      system for transcutaneous and open RFA, we now intend to transfer this technique
      to laparoscopic liver surgery. This study aimed to evaluate an electromagnetic
      navigation system for laparoscopic interventions using a perfusable ex vivo
      artificial tumor model. MATERIALS AND METHODS: First a special adapter was
      developed to attach the ultrasound and electromagnetic tracking-based navigation
      system to a laparoscopic ultrasound probe. The laparoscopic online navigation
      system was studied in a laparoscopic artificial tumor model using perfused
      porcine livers. Artificial tumors were created by injection of a mixture of 3%
      agarose, 3% cellulose, and 7% glycerol, creating hyperechoic lesions in
      ultrasound. RESULTS: This study showed that laparoscopic ultrasound-guided
      navigation is technically feasible. Even in cases of angulation of the ultrasound
      probe no disturbances of the navigation system could be detected. Artificial
      tumors were clearly visible on laparoscopic ultrasound and not felt during
      placement of the RFA probe. Anatomic landmarks and simulated 'tumors' in the
      liver could be reached safely. DISCUSSION: Laparoscopic RFA requires advanced
      laparoscopic ultrasound skills for accurate placement of the RFA probe. The use
      of an ultrasound-based, laparoscopic online navigation system offers the
      possibility of out-of-plane needle placement and could increase the safety and
      accuracy of punctures. The perfused artificial tumor model presented a realistic
      model for the evaluation of this new technique.

PMID- 18333218
TI  - Hyperbaric oxygen therapy and liver transplantation.
AB  - Liver transplantation is the treatment of choice for end stage liver disease and
      is often used for primary liver malignancies. The main limitation of its wider
      application is the availability of suitable donor organs. The use of marginal
      donor organs, split-liver transplantation and living-related liver
      transplantation techniques contribute to increase the donor pool. However, the
      use of these techniques is associated with a higher risk of post transplantation
      organ dysfunction, predominantly due to ischaemia, preservation and reperfusion
      injury (IPRI). A number of studies have demonstrated that hyperbaric oxygen (HBO)
      therapy influences IPRI and consequential acute cellular rejection. This article
      reviews the rationale of HBO therapy in the field of transplantation with
      particular emphasis on liver transplantation.

PMID- 18333221
TI  - Bimanual 'bi-finger' liver hanging maneuver: an alternative and safe technique
      for liver hanging.
AB  - BACKGROUND: Currently, a popular method for right hepatectomy is hepatic
      resection with the liver hanging maneuver. The aim of this study is to present an
      alternative and safe approach during this maneuver without using any instrument,
      thus avoiding injury. PATIENTS AND METHODS: From March 2005 to April 2006, a
      bimanual 'bi-finger' liver hanging maneuver (BBLHM) was planned in 22 right
      hepatectomies and the data were collected prospectively after operation. RESULTS:
      BBLHM was performed in 21/22 patients (95%). The maneuver was stopped in one
      patient, due to manual detection of an accessory hepatic vein during finger
      dissection in the retrohepatic space. This vein did not allow completion of the
      BBLHM. The indications for right hepatectomy included 11 primary hepatic tumors
      (52%), 8 metastatic right hepatic tumors (38%), and 2 hydatid cysts (9%).
      Intraoperative ultrasound (IOUS) demonstrated the normal anatomical configuration
      type of the hepatic veins. Bleeding occurred in one patient (4%), which was
      interrupted with the use of continuous 6/0 polypropylene suture. DISCUSSION: The
      most important step during the liver hanging maneuver is to develop the avascular
      space without any complication. In the present study, the index fingers were used
      instead of forceps during the blind dissection. BBLHM not only reduced the rate
      of damage to the hepatic veins but was also predictive for the presence of any
      accessory vein by its manual detection prior to injury. This maneuver allowed
      easier clamping of the hepatic veins and controllable hepatic resection.
      Dissection of retrohepatic space with the BBLHM produces a safer method, using
      both index fingers instead of a surgical instrument.

PMID- 18333222
TI  - Surgical therapy for testicular cancer metastatic to the liver.
AB  - In recent years improved cure rates have been achieved for testicular cancer. A
      better understanding of the biology of subtypes of testicular cancer and the
      introduction of surgical intervention has contributed greatly to how we currently
      approach a young man with testicular cancer. We describe here experience at our
      institution of the treatment, results and prognostic factors for testicular
      cancer metastases to the liver. Careful diagnostic work-up and planning of the
      therapy are required, in cooperation with an experienced team.

PMID- 18333223
TI  - The effects of surgical margin and edge cryotherapy after liver resection for
      colorectal cancer metastases.
AB  - BACKGROUND: A 1 cm margin seen at operation is typically the minimally acceptable
      margin for liver resections. Patients who fail to achieve this margin are
      routinely treated with edge cryotherapy at our unit. This paper aims to assess
      the benefit of edge cryotherapy on survival in patients with such suboptimal
      margins. PATIENTS AND METHODS: Between January 1990 and February 2006, 608
      patients underwent liver resection and/or cryotherapy for colorectal cancer
      metastases. All liver resections were performed using the CUSA transection
      method. Data on marginal status were available for 398 patients. Patient
      demographics, number and size of liver lesions, preoperative and postoperative
      carcinoembryonic antigen (CEA), extent of liver resection, margin status, site
      and date of recurrence, date of last follow-up and death were examined. RESULTS:
      There were 175 patients in the R0 group (>1 cm macroscopic and > or = 1 mm
      microscopic margin), 103 patients in the R1 group (>1 cm macroscopic and <1 mm
      microscopic margin) and 120 patients in the R2 group (< or = 1 cm macroscopic
      margin and received edge cryotherapy). After a median follow-up of 63 months,
      there were no significant difference between the 5-year survival rates for R0, R1
      and R2 (40%, 30% and 28%, respectively). CONCLUSION: As long as the surgical
      margin is clear macroscopically, the microscopic margin width does not affect
      survival. In patients with suboptimal margins, the addition of edge cryotherapy
      improves the prospect for long-term survival and may lower recurrence risk.

PMID- 18333225
TI  - The fate of autologous hepatocytes transplanted into spleen, pancreas, mesentery,
      stomach, and small bowel wall in pigs.

PMID- 18333224
TI  - MRI characterization of 124 CT-indeterminate focal hepatic lesions: evaluation of
      clinical utility.
AB  - OBJECTIVE: To evaluate the diagnostic yield of MRI performed for characterization
      of focal hepatic lesions that are interpreted as indeterminate on CT. PATIENTS
      AND METHODS: In a retrospective investigation, 124 indeterminate focal hepatic
      lesions in 96 patients were identified on CT examinations over 5 years from 1997
      to 2001. All patients had MRI performed for the liver within 6 weeks of their CT
      examination. CT and MR images were reviewed independently by two separate groups
      of two radiologists. The value of MRI in characterizing these lesions was
      assessed. Diagnoses were confirmed based on histology, characteristic imaging
      features, and clinical follow-up. RESULTS: MRI definitely characterized 73
      lesions (58%) that were indeterminate on CT. MRI was accurate in 72/73 of these
      lesions. MRI could not definitely characterize 51 lesions (42%). Ten lesions were
      not visualized on MRI, and follow-up imaging confirmed that no lesion was present
      in eight of these cases (pseudolesions). CONCLUSION: MRI is valuable for the
      characterization of indeterminate focal hepatic lesions detected on CT.

PMID- 18333226
TI  - The role of (99m)technetium-labelled hepato imino diacetic acid (HIDA) scan in
      the management of biliary pain.
AB  - OBJECTIVE: To assess the outcome of laparoscopic cholecystectomy on the basis of
      an abnormal provocative (99m)technetium-labelled hepato imino diacetic acid
      (HIDA) scan for patients with typical biliary pain and normal trans-abdominal
      ultrasound (TUS) scan. PATIENTS AND METHODS: Prospective data were collected for
      1201 consecutive patients with typical biliary symptoms. Patients who were found
      to have a normal TUS and upper GI endoscopy subsequently underwent
      cholescintigraphy (HIDA scan). Patients with an abnormal HIDA scan, i.e.<40%
      ejection fraction with Sincalide (cholecystokinin octapeptide)--were offered
      cholecystectomy. Symptoms and histology were reviewed postoperatively. RESULTS:
      In all, 48/1201 (4%) patients with typical biliary symptoms had a normal
      ultrasound and endoscopy; 35/48 patients had an abnormal provocative HIDA scan
      and all underwent laparoscopic cholecystectomy. Histology in all cases revealed
      chronic cholecystitis and 18 patients had sludge or microlithiasis within the
      gallbladder. At 6-week follow-up, 31 of the 35 patients were completely
      asymptomatic or improved. Furthermore, 79% of patients remained symptom-free or
      improved at a median follow-up of 28.5 months (range 4-70). CONCLUSIONS: HIDA
      scan is a useful clinical tool as an adjunct to the diagnosis and management of
      patients who present with typical biliary pain and a normal TUS scan.

PMID- 18333227
TI  - Microbiological assessment of bile during cholecystectomy: is all bile infected?
AB  - AIMS: To determine the prevalence of bactibilia in patients undergoing
      cholecystectomy and to relate the presence or absence of organisms to the
      preoperative and postoperative course. PATIENTS AND METHODS: Patients undergoing
      cholecystectomy under the care of a single consultant surgeon during a continuous
      5-year period were identified from a prospectively maintained departmental
      database. Symptoms, clinical signs, findings of investigations, details of
      treatment and postoperative care were noted. Risk factors for bactibilia (acute
      cholecystitis, common duct stones, emergency surgery, intraoperative findings and
      age > 70 years) were documented. Patients were divided according to the presence
      (B + ) or absence (B-) of bacteria on culture of their bile. RESULTS: In all,
      128/180 (70%) of cholecystectomies had full data available for analysis. Bacteria
      were identified in the bile of 20 (15.6%) patients (B+ group). The B+ group was
      significantly older at 63.78+/-9.7 versus 61.62+/-13.9 (p<0.05) and contained
      significantly fewer females than the B- group (p<0.05). All 20 patients (100%) in
      the B+ group had > or = 1 risk factor, while these factors were present in only
      29/108 (30.3%) of patients in the B- group (p<0.05). The overall incidence of
      infective complications was 20% in the B+ group compared with 0.9% in the B-
      group (p<0.05) and the bile-related infections were higher in the B+ group
      (p<0.05). CONCLUSIONS: The study demonstrated that while patients with
      complicated gallstone disease frequently exhibit bactibilia, patients with
      uncomplicated cholelithiasis have aseptic bile. The findings would suggest that
      prophylactic antibiotics should be limited to patients with risk factors for
      bactibilia.

PMID- 18333228
TI  - Pancreatico-duodenectomy for complicated groove pancreatitis.
AB  - OBJECTIVES: Groove pancreatitis (GP) describes a form of segmental pancreatitis,
      which affects the pancreatic head at the interface with the duodenum, and is
      frequently associated with ectopic pancreatic tissue in the duodenal wall. We
      present a series of symptomatic patients with complicated GP who underwent
      pancreaticoduodenectomy, and review the diagnostic challenges, imaging
      modalities, pathological features and clinical outcome of this rare condition.
      PATIENTS AND METHODS: This was a prospective case base study of clinical,
      radiological and pathological data collected between the years 2000 and 2005 on
      patients diagnosed with severe GP--confirmed by histopathological examination
      following pancreaticoduodenectomy. RESULTS: In total 11 patients were included,
      presenting with chronic abdominal pain (n=11), gastric outlet obstruction (n=5)
      and jaundice (n=1). Exocrine dysfunction with associated weight loss (median > 9
      kg) was present in 10 patients, and type 2 diabetes in 2 patients. Radiological
      imaging (CT/MRCP/EUS) provided complementary investigations and correlated well
      with classic histopathological findings (duodenal wall thickening, mucosal
      irregularity and Brunner's gland hyperplasia, duodenal wall cysts and pancreatic
      heterotropia). Following pancreaticoduodenectomy (median follow-up period 52
      weeks) all patients experienced significant pain alleviation and weight gain
      (average 3 kg at 2 months). CONCLUSION: Pancreaticoduodenectomy is associated
      with significant improvements in weight gain and alleviates the chronic pain
      associated with severe GP.

PMID- 18333229
TI  - Percutaneous management of necrotizing pancreatitis.
AB  - The management algorithm surrounding necrotizing pancreatitis has altered
      radically in the last 15 years in response to evolving concepts, improved
      understanding and the development of minimally invasive techniques, including
      percutaneous necrosectomy, and laparoscopic or EUS-guided cystgastrostomy. This
      article discusses the emerging role of minimally invasive techniques, key to
      which is an understanding of the evolving pathology of post acute, necrosis
      associated fluid collections in pancreatitis. A dynamic and multi-modal
      management approach is presented, the aim of intervention being the 'adequate and
      maintained control of sepsis': the choice of technique dependent on the
      anatomical position, the ratio of solid to fluid components within the
      collection, and in particular the degree of systemic organ dysfunction.

PMID- 18333232
TI  - Classification of liver and pancreatic trauma.
AB  - The liver is the most frequently injured intra-abdominal organ and associated
      injury to other organs increases the risk of complications and death. This has
      highlighted the critical need for an accurate classification system as a basis
      for the clinical decision-making process. Several classification systems have
      been proposed in an attempt to incorporate the aetiology, anatomy and extent of
      injury and correlate it with subsequent clinical management and outcome. The
      widely accepted Organ Injury Scale is based on anatomical criteria that quantify
      the disruption of the liver parenchyma and defines six groups which may influence
      management strategies and relate to outcome. The less common pancreatic injury
      remains a major source of morbidity and mortality due to the likelihood of
      associated solid or hollow-organ injuries. The implication of a delay in
      diagnosis and management emphasizes the need for an accurate classification
      system. The Organ Injury Scale is widely used for pancreas trauma and recognizes
      the importance of progressive parenchymal injury and in particular ductal injury.
      Advances in imaging techniques have led to the development of newer radiological
      classification systems; however, validation of their accuracy remains to be
      proven. An accurate classification of liver and pancreatic trauma is fundamental
      for the development of treatment protocols in which clinical decisions are based
      on the severity of injury.

PMID- 18333233
TI  - Living donor liver transplantation.
AB  - The introduction of living donor liver transplantation (LDLT) has been one of the
      most remarkable steps in the field of liver transplantation (LT). First
      introduced for children in 1989, its adoption for adults has followed only 10
      years later. As the demand for LT continues to increase, LDLT provides life
      saving therapy for many patients who would otherwise die awaiting a cadaveric
      organ. In recent years, LDLT has been shown to be a clinically safe addition to
      deceased donor liver transplantation (DDLT) and has been able to significantly
      extend the scarce donor pool. As long as the donor shortage continues to
      increase, LDLT will play an important role in the future of LT.

PMID- 18333234
TI  - Neoadjuvant chemoradiation in patients with pancreatic adenocarcinoma.
AB  - In spite of the high mortality in pancreatic cancer, significant progress is
      being made. This review discusses multimodality therapy for patients with
      pancreatic cancer. Surgical therapy currently offers the only potential monomodal
      cure for pancreatic adenocarcinoma. However, only 10-20% of patients present with
      tumors that are amenable to resection, and even after resection of localized
      cancers, long-term survival is rare. The addition of chemoradiation therapy
      significantly increases median survival. To achieve long-term success in treating
      this disease it is therefore increasingly important to identify effective
      neoadjuvant/adjuvant multimodality therapies. Preoperative chemoradiation for
      potentially resectable pancreatic cancer has the following advantages: (1)
      neoadjuvant treatment would eliminate the delay of adjuvant treatment due to
      postoperative complications; (2) neoadjuvant treatment could avoid unnecessary
      surgery for patients with metastatic disease evident on restaging after
      neoadjuvant therapy; (3) down-staging after neoadjuvant therapy may increase the
      likelihood of negative surgical margins; and (4) neoadjuvant treatment could
      prevent peritoneal tumor cell implantation and dissemination caused during
      surgery. This review systematically summarizes the current status, controversies,
      and prospects of neoadjuvant treatment of pancreatic cancer.

PMID- 18333236
TI  - Liver hanging maneuver for right hemiliver in situ donation--anatomical
      considerations.
AB  - BACKGROUND: An anatomical study was carried out to evaluate the safety of the
      liver hanging maneuver for the right hemiliver in living donor and in situ
      splitting transplantation. During this procedure a 4-6 cm blind dissection is
      performed between the inferior vena cava and the liver. Short subhepatic veins
      entering the inferior vena cava from segments 1 and 9 could be torn with
      consequent hemorrhage. MATERIALS AND METHODS: One hundred corrosive casts of
      livers were evaluated to establish the position and diameter of short subhepatic
      veins and the inferior right hepatic vein. RESULTS: The average distance from the
      right border of the inferior vena cava to the opening of segment 1 veins was
      16.7+/-3.4 mm and to the entrance of segment 9 veins was 5.0+/-0.5 mm. The width
      of the narrowest point on the route of blind dissection was determined, with the
      average value being 8.7+/-2.3 mm (range 2-15 mm). DISCUSSION: The results show
      that the liver hanging maneuver is a safe procedure. A proposed route of
      dissection minimizes the risk of disrupting short subhepatic veins (7%).

PMID- 18333235
TI  - Liver transplantation for acute hepatic failure.
AB  - There are numerous causes of acute hepatic failure (AHF). Cerebral edema,
      coagulopathy, renal failure, metabolic disturbances and infection are the main
      clinical sequelae. Patients with AHF should be stabilized when first encountered
      and transferred to the nearest liver transplant center, as AHF progresses quickly
      and is often fatal. There are few adequate medical interventions and care of
      patients with AHF is supportive until spontaneous recovery ensues. If recovery
      does not appear to occur, most causes of AHF are well accepted indications for
      liver transplantation.

PMID- 18333237
TI  - Surgical treatment of liver hydatid cysts.
AB  - BACKGROUND: The surgical treatment technique for liver hydatic cyst (LHC) cannot
      be standardized, and the surgical technique should be tailored according to the
      extent of the cyst and any adjunct complications of hydatid disease. PATIENTS AND
      METHODS: All patients were treated with albendazole (10 mg/kg/day) for 15 days
      preoperatively. Total pericystectomy was performed in three patients (7%).
      Partial cystectomy and its modifications were performed in the remaining 41
      patients (93%). RESULTS: A total of 44 patients were operated on for LHC between
      December 1998 and October 2004 in our center. Patients were evaluated with
      ultrasonography and computed tomography scan to determine the extent of the
      disease and preoperative staging. Twenty-four (53%) of these patients were women
      and 20 were men (median age, 52.5 years; range, 19-81 years). The majority of
      patients (n=27) had 1 cyst, and the remaining 17 patients had multiple cysts. In
      four patients (9.1%), daughter cysts were found in the biliary system, and
      abscesses were present in three patients (7%). Biliary fistula was the most
      frequent complication (n=5). Three patients had wound infections. Follow-up was
      complete for 33 patients (75%). The mean postoperative follow-up was 11.9+/-10.8
      months; there were four recurrences during this time. DISCUSSION: The aim should
      be to provide complete drainage and obliteration of the cavity. Bile leak and
      biliary obstruction may complicate the postoperative course if bile leakage into
      the peritoneal cavity and obstruction in the biliary system are missed.

PMID- 18333238
TI  - Efficacy of antibiotic penetration into pancreatic necrosis.
AB  - BACKGROUND: Infection of pancreatic necrosis is the most dangerous complication
      of acute necrotizing pancreatitis. Infection is undoubtedly caused by the
      endogenous flora of the host. This is why prophylaxis with a broad-spectrum
      antibiotic is considered an effective procedure. However, two aspects should be
      taken into consideration when choosing the antibiotic; it should have the
      spectrum of action consistent with the pathogens and it should penetrate
      effectively to the necrotic tissue of the pancreas. The aim of the study was to
      estimate the efficacy of piperacillin/tazobactam penetration into pancreatic
      necrosis in patients who received intravenous infusion of piperacillin/tazobactam
      at a dose of 4.5 g every 8 h for 14-21 days, as the prophylaxis in the treatment
      of acute necrotizing pancreatitis. PATIENTS AND METHODS: Necrotic tissue of the
      pancreas and the inflammatory ascites surrounding the pancreas were derived from
      15 patients (male, 10; female, 5; mean age 46 years), who underwent laparatomy
      due to pancreatic necrosis after treatment for 14-21 days. Tissue/fluid samples
      were investigated for the concentration of the antibiotic by
      fluoroscopic/spectroscopic methods of registration in an HPLC system. RESULTS:
      The mean concentration of piperacillin/tazobactam was established as 120 mg/kg
      (SD+/-34) in the necrotic pancreatic tissue and as 183 mg/kg (SD+/-37) in the
      inflammatory pancreatic ascites. CONCLUSIONS: In patients with acute necrotizing
      pancreatitis, the study indicates effective penetration of
      piperacillin/tazobactam to the necrotic pancreatic tissue and to the inflammatory
      ascites surrounding the pancreas.

PMID- 18333239
TI  - Distal pancreatic resection: technical differences between open and laparoscopic
      approaches.
AB  - Open distal pancreatic resection has been performed over the years for management
      of patients with a variety of pancreatic disorders. However, the technique is
      usually not performed in the same way by all surgeons. In recent years, the
      laparoscopic approach has been introduced with all the advantages of a minimally
      invasive procedure. The primary differences between the open and laparoscopic
      approaches are the method of access, the method of exposure, and the extent of
      operative trauma. The clinical advantages of the laparoscopic approach are the
      reduced length hospitalization, the reduction in postoperative pain, absence of
      wound-related complications and faster recovery.

PMID- 18333240
TI  - Combined endoscopic and laparoscopic ultrasound as preoperative assessment of
      patients with pancreatic cancer.
AB  - BACKGROUND: An accurate pre-therapeutic assessment of the resectability in
      pancreatic cancer patients is essential to reduce the number of futile surgical
      explorations. The aim of this study was to assess the combination of endoscopic
      ultrasound (EUS) and laparoscopic ultrasound (LUS) regarding the detection of
      patients with non-resectable tumours. PATIENTS AND METHODS: From 2002 to 2004,
      179 consecutive patients with pancreatic cancer referred for surgical treatment
      were eligible. Thirty-one (17%) patients were excluded due to co-morbidity and
      poor performance status. Two patients (1%) were excluded due to metastasis seen
      on CT scans prior to referral. Thus, 146 patients entered the study. Patients
      were first examined with EUS followed by LUS, if EUS found no signs of non
      resectability. Only patients with tumours found to be resectable or possibly
      resectable at EUS and LUS were offered surgical treatment. Resectability criteria
      were defined prior to the study. RESULTS: In all, 108 (74%) patients had non
      resectable tumours by the pre-defined criteria. EUS identified 68 (63%) patients
      and LUS identified an additional 26 (24%) patients. Thus, a total of 94 (87%)
      patients were non-resectable at either EUS or LUS. Fifty-two (36%) patients
      underwent surgery. Six patients had surgical exploration and three patients had
      palliative surgery. Forty-three patients (29%) were resected with curative
      intention, of whom 38 (88%) had an R0 resection and 5 (12%) had a palliative
      resection. DISCUSSION: The combination of EUS and LUS is accurate in identifying
      the non-resectable patients and has a high predictive value for complete
      resection.

PMID- 18333241
TI  - Radiofrequency ablation in pancreatic cancer.
AB  - INTRODUCTION AND AIM: Radiofrequency ablation (RFA) is effective in the treatment
      of unresectable hepatic tumors and promising results have also been described in
      tumors of kidney, lung, brain, prostate, and breast. The radiofrequency
      destruction of solid pancreatic tumors sounds logical but also seems risky due to
      the friable pancreatic parenchyma, the fear of pancreatitis and the prejudiced
      myth of 'the pancreas is not your friend'. PATIENTS AND METHODS: We present our
      initial experience and we describe our technique during intraoperative RFA in
      four patients with locally advanced and unresectable pancreatic adenocarcinoma
      (head of pancreas, three; body-tail, one; diameter, 3-12 cm). In all the
      patients, the RFA was followed by bypass palliative procedures
      (cholecystojejunostomy and Brown's anastomosis and/or gastrojejunostomy). A
      drainage tube was left close to the ablated area. Serum amylase and fluid amylase
      (drain) were measured for 5-7 days postoperatively. Sandostatin was also
      administered prophylactically for 3-5 days. RESULTS: The postoperative period was
      uneventful in all the patients, without complications or evidence of
      pancreatitis. The post RFA CT scan showed remarkable changes in the density and
      the characteristics of the tumors in all the patients. All the patients are
      alive, at 12, 8, 5 and 3 months postoperatively, respectively. In one patient
      (with cancer of the body of the pancreas) who was receiving morphine because of
      intolerable pain, significant pain relief has been observed. CONCLUSIONS: From
      our initial results, RFA seems to be a feasible, potentially safe and promising
      option in patients with locally advanced and unresectable pancreatic cancer.
      Nevertheless, larger series of cases are needed to secure our encouraging
      results.

PMID- 18333242
TI  - Extraskeletal osteosarcoma located to the gallbladder.
AB  - Extraskeletal osteosarcoma is a rare malignant soft tissue tumour. At open
      cholecystectomy performed for gallstones, a 61-year-old woman was found to have
      osseous tissue in the wall of the gallbladder. Histopathological examination of
      the specimen revealed a focus of extraskeletal osteosarcoma. The patient
      developed widespread intra-abdominal metastases 5 months after the operation, and
      died of pulmonary deposits at 9 months. Although osteosarcoma has rarely been
      reported at other extraskeletal sites, this appears to be the first case of a
      primary tumour in the gallbladder.

PMID- 18333243
TI  - Liver transplantation for metastases from a bile duct carcinoid.
AB  - BACKGROUND: A 29-year-old woman who presented with fatigue and jaundice was found
      to have an obstructing mass at the bifurcation of the bile duct. The patient
      underwent a successful left hepatectomy with resection of the bile duct
      bifurcation and a reconstruction with a right hepaticojejunostomy. Pathology
      revealed an atypical carcinoid tumour of the left extrahepatic bile duct, with
      perineural and lymphatic invasion. The patient subsequently developed multiple
      metastases in the remaining liver. METHODS: In the absence of extrahepatic
      disease, the patient underwent a successful liver transplant. RESULTS: Two years
      later she remains disease-free. DISCUSSION: To our knowledge this is the first
      report of a biliary carcinoid treated with hepatectomy and finally with liver
      transplantation, with excellent results. The biological behaviour of these rare
      tumours mandates aggressive surgical management.

PMID- 18333244
TI  - Gallbladder-duodenal fistula presenting with liver abscess and upper
      gastrointestinal bleeding.
AB  - BACKGROUND: Bilio-enteric communications leading to liver abscess formation are
      encountered rarely and are therefore not easily suspected by the attending
      physician. CASE OUTLINE: A bilio-enteric communication involving the gallbladder
      and the duodenum presented as a septic event with upper gastrointestinal bleeding
      in a 71-year-old man who was wrongly thought to have undergone a previous
      cholecystectomy. A pyogenic bacterial liver abscess developed from the fistula in
      the absence of biliary obstruction. The patient was treated surgically with
      disconnection of the fistula and drainage of the abscess. DISCUSSION: The liver
      abscess presumably arose as a consequence of contamination of the bile via the
      cholecysto-duodenal fistula. The previous operation is likely to have been a
      simple cholecystostomy.

PMID- 18333245
TI  - Regarding 'Liver cell adenoma and liver cell adenomatosis' by Ludger Barthelmes
      and Iain S. Tait.

PMID- 18333246
TI  - Ascariasis-induced eosinophilic cholecystitis--a unique case.

PMID- 18333247
TI  - Isolated gallbladder metastatic melanoma.

PMID- 18333248
TI  - Therapeutic considerations in obstructive jaundice due to hepatic artery
      aneurysm.

PMID- 18333250
TI  - Liver surgery for noncolorectal nonneuroendocrine metastases.

PMID- 18333251
TI  - Surgical treatment of liver metastases from pancreatic cancer.
AB  - Pancreatic cancer is a disease with a poor prognosis. Most patients are diagnosed
      at an advanced and unresectable stage. Even if the primary cancer is radically
      removed, postoperative recurrence frequently occurs. Generally, metastatic liver
      tumors from pancreatic cancer are not indicated for surgical treatment. Here we
      evaluate the results of performing hepatectomy for liver metastases of pancreatic
      cancer. In our institute, six patients with liver metastases from pancreatic
      cancer were treated by partial hepatectomy. Overall 1-, 3- and 5-year survival
      rates of six patients after hepatectomy were 66.7%, 33.3% and 16.7%,
      respectively, and one patient was alive for 65.4 months. Performing a hepatectomy
      for liver metastases of pancreatic cancer, when combined with a pancreas
      resection, was recently considered to be a safe operation, and one that might
      offer prolonged survival for highly selected patients with curative resection of
      liver metastases. In the future, it will be necessary to develop new multi
      modality therapies to improve the prognosis of pancreatic cancer.

PMID- 18333252
TI  - Hepatic resection for the treatment of liver metastases in gastric carcinoma:
      review of the literature.
AB  - This article presents a review of the literature on hepatic resection for the
      treatment of liver metastases in gastric carcinoma, and discusses the
      indications, mortality rates, prognostic factors and long-term results. Reports
      on hepatectomy for liver metastases from gastric cancer are rare, the results are
      disappointing, and further studies are required.

PMID- 18333253
TI  - Hepatic resection for metachronous metastases from ovarian carcinoma.
AB  - Recently, several authors have reported that optimal primary cytoreduction of
      both hepatic and extrahepatic disease is not only feasible but improves survival.
      However, the role of hepatic resection in combination with secondary
      cytoreduction for epithelial ovarian cancer is unclear. Patients with recurrent
      ovarian cancer and metachronous intrahepatic metastases are often evaluated by a
      multidisciplinary team at the Mayo Clinic comprising pelvic and hepatobiliary
      surgeons for consideration of cytoreductive surgery. The purpose of this report
      is to update the outcome of cytoreductive surgery including hepatic resection for
      patients with metastatic ovarian carcinoma.

PMID- 18333254
TI  - Surgery for liver metastases from breast cancer.
AB  - Liver metastases develop in approximately half of women with metastatic breast
      cancer, and are typically associated with metastases at other sites, indicating
      advanced disease and poor prognosis. Whenever possible, hormonal therapy should
      be administered, until resistance develops. Several series in the literature have
      reported a poor effect of chemotherapy alone in patients with metastatic breast
      cancer, therefore liver surgery could be considered as an adjuvant treatment to
      systemic therapy in highly selected patients. This study looked at recent case
      series in the literature, and analysed prognostic factors and indications for
      surgery.

PMID- 18333255
TI  - Outcome following hepatic resection of metastatic renal tumors: the Paul Brousse
      Hospital experience.
AB  - BACKGROUND: As many as 50% of patients with renal cell carcinoma (RCC) will
      develop systemic metastases. When hepatic metastases from RCC present in a
      resectable distribution, our group and other groups have previously shown that
      some patients benefit from curative hepatic resection. In this report we update
      our own experience and summarize the literature published to date on this topic.
      PATIENTS AND METHODS: From 1982 to 2005, 19 patients (9 men, 10 women, median age
      50 years) with hepatic metastases from RCC were treated with hepatic resection at
      our institution. In 14 (74%) of the 19 patients the presentation of hepatic
      metastases was metachronous. Seven (37%) patients had been or were simultaneously
      treated for extrahepatic metastases. The mean tumor number was 2 and the mean
      diameter of the largest metastasis was 73 mm. RESULTS: Margin-negative resection
      was achieved in 17 (89%) of 19 cases. Postoperative morbidity and mortality rates
      were 32% and 5%, respectively. At a median follow-up interval of 26 months, 15
      patients recurred with a mean time to recurrence of 12 months. The 3-year and 5
      year disease-free survival rates were 25% and 25%, respectively; 3-year and 5
      year overall survival rates were 52% and 26%, respectively, with one patient
      alive 5 years following first hepatectomy. Study factors which predicted
      prolonged survivals included male sex and maximum tumor diameter </=5 cm.
      DISCUSSION: The overall survival rates in our series (3-year, 52%; 5-year, 26%)
      and in a complete review of the literature (3-year, 24%; 5-year, 18%) indicate
      that selected patients with hepatic metastases from RCC benefit from hepatic
      resection.

PMID- 18333256
TI  - Liver resection for hepatic metastases from adrenocortical carcinoma.
AB  - Liver metastases from adrenocortical carcinoma are very rare and no clear
      indications for surgery exist. The aim of the present work was to define surgical
      indications for these neoplasms. All the patients submitted to hepatic resection
      for liver metastases from adrenal carcinoma reported in the literature (PubMed
      source) from 1978 to 2005 were considered for the present study. Forty-eight
      patients were found in the period of study, but it was only possible to obtain
      certain data for nine patients (18.7%). The data investigated suggest that
      metachronous metastases, developed after a minimum of 1 year from the primary
      tumor, and completely removable, may represent an indication for surgery -
      although this still needs to be proved.

PMID- 18333257
TI  - Liver resection for metastasis due to malignant mesenchymal tumours.
AB  - While liver resection for colorectal metastases has shown promising long-term
      survival, data for metastasectomy in sarcoma and leiomyosarcoma patients have not
      yielded the same optimism. Due to the rarity of the tumour entity it has always
      been difficult to provide significant data. Advances in tumour classification
      suggest that most of the metastases formerly classified to be of sarcomatoid and
      especially leiomyosarcomatoid origin are actually metastases of GISTs (gastro
      intestinal stromal tumours). Neoadjuvant/adjuvant imatinib therapy might improve
      overall survival and enable surgeons to provide resections in previously
      unresectable patients. Only R0 resection has been proven to prolong survival so
      far, with a long disease-free interval as the only independent predictor of
      outcome.

PMID- 18333258
TI  - The role of liver resections for metastases from lung carcinoma.
AB  - Liver resections are usually considered the treatment of choice for colorectal
      and neuroendocrine metastases. Recently, the morbidity and mortality rates for
      liver surgery have dramatically decreased. Therefore, hepatic resection has been
      applied in selected cases of non-colorectal, non-neuroendocrine hepatic
      metastases. We report our experience with three cases of liver metastases from
      lung carcinoma and review the literature, to evaluate the role of liver surgery
      for this indication.

PMID- 18333259
TI  - Immunomodulation in surgical practice.
AB  - BACKGROUND: Immunomodulation may represent a potential way to improve surgical
      outcome. These types of interventions should be based on detailed knowledge of
      the underlying mechanisms involved. The aim of the present review is to summarize
      some experience on the acute phase response, potential ways of intervention and
      experiences from critical illness and HPB disease. DISCUSSION: Mechanisms of the
      acute phase response are discussed including the individual parameters and local
      changes that take part. Mechanisms involved in failure of the gut barrier are
      presented and include changes in gut barrier permeability, effects on gut
      associated immunocompetent cells, and systemic implications. As examples of HPB
      disease, mechanisms of the acute phase response and potential ways of
      intervention in obstructive jaundice and acute pancreatitis are discussed.
      Nutritional pharmacology and lessons learned from immunomodulation and
      immunonutrition in critical illness and major abdominal surgery, including upper
      GI and HPB surgery, are referred to. Overall, immunomodulation represents a
      potential tool to improve results but requires a thorough mapping of underlying
      mechanisms in order to achieve individualized treatment or prevention based on
      patients' specific needs.

PMID- 18333260
TI  - Lung metastases after liver resection or cryotherapy for hepatic metastasis from
      colorectal cancer--there is a difference!
AB  - BACKGROUND: The most common site of colorectal extra-abdominal metastases is the
      lung. The relative risk of lung metastases after resection and cryotherapy has
      not previously been compared. METHODS: All patients underwent an extensive
      preoperative staging including clinical examination, abdominal computed
      tomography (CT) and abdominal angio-CT to assess their hepatic disease. Two
      groups of patients were compared in this study (hepatic resection alone and
      hepatic cryotherapy with or without resection). A retrospective analysis of
      prospectively collected data was performed to assess the incidence and disease
      free interval of pulmonary metastasis after surgical treatment of colorectal
      liver metastasis. RESULTS: This paper clearly shows two differences regarding
      pulmonary metastases between patients treated with resection only and cryotherapy
      with or without resection. Among the 10 clinical variables, cryotherapy had the
      greatest correlation with pulmonary metastases (p=0.004). A patient who undergoes
      hepatic resection only has a probability of 35% for developing pulmonary
      recurrence, compared with 51% following cryotherapy. Cryotherapy was also
      independently associated with shorter pulmonary disease-free interval (p=0.036).
      CONCLUSION: There clearly is a higher risk of pulmonary metastasis after
      cryotherapy than after resection, whether this is related to selection of
      patients or a direct deleterious procedural effect requires more study.

PMID- 18333261
TI  - Biliary reconstruction using non-penetrating, tissue everting clips versus
      conventional sewn biliary anastomosis in liver transplantation.
AB  - BACKGROUND: Biliary complications occur following approximately 25% of liver
      transplantations. Efforts to decrease biliary complications include methods
      designed to diminish tissue ischemia. Previously, we reported excellent short
      term results and decreased biliary anastomosis time in a porcine liver transplant
      model using non-penetrating, tissue everting clips (NTEC), specifically VCS
      clips. METHODS: We examined the incidence of biliary anastomotic complications in
      a group of patients in whom orthotopic liver transplantation was performed with
      biliary reconstruction using NTEC and compared that group to a matched group
      treated with biliary reconstruction via conventional end-to-end sewn
      choledochocholedochostomy. Patients were matched in a 1:2 fashion by age at
      transplantation, disease etiology, Child-Turcot-Pugh scores, MELD score or UNOS
      status (prior to 1998), cold and warm ischemia times, organ donor age, and date
      of transplantation. RESULTS: Seventeen patients had clipped anastomosis and 34
      comparison patients had conventional sewn anastomosis. There were no differences
      between groups in terms of baseline clinical or demographic data. The median time
      from completion of the hepatic artery anastomosis to completion of clipped versus
      conventional sewn biliary anastomosis was 45 (interquartile range = 20 min)
      versus 47 min (interquartile range = 23 min), respectively (p=0.12). Patients
      were followed for a mean of 29 months. Biliary anastomotic complications,
      including leak or anastomotic stricture, were observed in 18% of the clipped
      group and 24% of the conventional sewn group. CONCLUSIONS: Biliary reconstruction
      can be performed clinically using NTEC as an alternative to conventional sewn
      biliary anastomoses with good results.

PMID- 18333262
TI  - Postoperative changes in protein-induced vitamin K absence or antagonist II
      levels after hepatectomy in patients with hepatocellular carcinoma: relationship
      to prognosis.
AB  - BACKGROUND: alpha-Fetoprotein (AFP) has been used as a marker for hepatocellular
      carcinoma (HCC). However, AFP levels are often high in patients with chronic
      hepatitis or cirrhosis. Protein-induced vitamin K absence or antagonist II (PIVKA
      II) is more sensitive for the diagnosis of HCC and prediction of patient
      survival. Changes in these markers after treatment may reflect treatment
      curability and patient outcome. METHODS: We conducted a retrospective analysis of
      prognosis of 63 HCC patients with high preoperative levels of AFP and PIVKA-II
      who underwent hepatectomy and examined the relationship between postoperative
      changes in both markers at 1 month and patient survival. Subjects were divided
      into three groups according to changes in these tumour markers after hepatectomy:
      normalization (N) group, decreased but still above the normal level (D) group and
      unchanged (U) group. RESULTS: There were no significant differences in the
      numbers of patients who developed tumour recurrence between changes in AFP and
      PIVKA-II. Survival analysis showed no significant differences in tumour-free and
      overall survivals between groups with respect to AFP level. The PIVKA-II-N group
      showed significantly better tumour-free and overall survival compared with the D
      and U groups (p<0.01). Multivariate analysis that included other prognostic
      factors identified changes in PIVKA-II level as a significant and independent
      prognostic factor associated with overall survival. DISCUSSION: Although changes
      in AFP did not correlate with patient prognosis, normalization of PIVKA-II was
      significantly associated with good patient survival after hepatectomy.
      Normalization of PIVKA-II after hepatectomy reflected the efficacy of treatment
      and is a suitable predictor of prognosis in HCC patients.

PMID- 18333263
TI  - Central pancreatectomy for benign pancreatic lesions.
AB  - INTRODUCTION: Traditional resections for pancreatic malignancies include distal
      pancreatectomy with splenectomy and pancrearicoduodenectomy (PD). Alternative
      resections for benign pancreatic disease are used to minimize the resection of
      normal pancreatic and splenic parenchyma. This study describes the use of central
      pancreatectomy (CP) in 10 patients. METHODS: A retrospective chart review of all
      patients undergoing CP between May 1999 and February 2004 was undertaken.
      RESULTS: Ten patients (eight female, two male) underwent CP for benign pancreatic
      disease. Median age was 59 years (range 21-75). Eight patients presented with
      abdominal pain, two of whom also had weight loss. One patient each presented with
      hypoglycemia and as an incidental finding. Median operative time was 255 min
      (range 160-380 min). Proximal pancreatic remnant was stapled in five and oversewn
      in five. Distal pancreatic remnant was managed with pancreaticojejunostomy in six
      patients and pancreatjcogastrostomy in four patients. There were no 30-day
      mortalities. Pancreatic fistula developed in four patients (40%), and all
      resolved without operative intervention. All patients are alive with no
      recurrence and no new endocrine or exocrine dysfunction. CONCLUSION: CP has
      similar morbidity and mortality rates to traditional pancreatic resections and
      may offer a lower incidence of diabetes and exocrine insufficiency.

PMID- 18333264
TI  - Solid pseudopapillary neoplasm of the pancreas: a single institution experience
      of 14 cases.
AB  - Solid pseudopapillary neoplasm of pancreas (SPN) is a rare entity; therefore
      proper diagnosis, evaluation and formulation of treatment protocols is difficult.
      A total of 14 cases were diagnosed and treated at our institute over a 10-year
      period (1992-2002). A retrospective study of all these cases was performed with
      respect to age group most frequently affected, sex ratio, common presenting
      symptoms and signs, investigative protocols, pathological features, treatment
      offered, outcome and prognosis. All the 14 patients were females, with a median
      age of 20 years (range 13-45 years). The commonest presenting symptom was
      abdominal pain. All these patients underwent surgical exploration; 13 patients
      underwent resection of the tumour. The average length of postoperative hospital
      stay was 10.3 days. Significant postoperative morbidity was seen in only one
      case. There was no postoperative mortality. All these patients who underwent
      resection were disease-free on follow-up ranging from 6 to 96 months (median 36
      months).

PMID- 18333265
TI  - Cholangiocarcinoma, renal cell carcinoma and parathyroid adenoma found
      synchronously in a patient on long-term methotrexate.
AB  - Cases of patients developing lymphoma and cutaneous neoplasms after long-term
      methotrexate therapy are well documented in the literature; however, there are no
      reported cases of other neoplasms resulting from methotrexate therapy. A 52-year
      old woman who had been on methotrexate for 9 years for psoriatic arthritis was
      found to have abnormal liver function tests on screening. Investigation with
      ultrasound, CT scanning and MRCP showed a hilar cholangiocarcinoma and a
      synchronous right renal tumour. A left hemi-hepatectomy extended to segments 5
      and 8 with the formation of a hepaticojejunostomy was performed for a poorly
      differentiated infiltrative hilar cholangiocarcinoma. This was combined with a
      right radical nephrectomy for a T1 renal cell adenocarcinoma. Postoperative
      vomiting was subsequently found to be due to hypercalcaemia and primary
      hyperparathyroidism. A parathyroid adenoma was later excised. It seems likely
      that treatment with methotrexate was causal in the development of these three non
      cutaneous neoplasms-two malignant and one benign.

PMID- 18333266
TI  - Idiopathic fibrosing pancreatitis associated with ulcerative colitis.
AB  - Idiopathic fibrosing pancreatitis has been associated with Sjogren's syndrome,
      primary biliary cirrhosis and primary sclerosing cholangitis. This condition
      frequently develops in childhood and youth, and has also been related to
      ulcerative colitis and pericholangitis. Pancreatic complications have been rarely
      described as systemic complications of ulcerative colitis. A 25-year-old man
      presented with epigastric pain and jaundice. Abdominal ultrasonography, computed
      tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and
      endoscopic retrograde cholangiopancreatography (ERCP) revealed a diffuse
      enlargement of the pancreas, filiform distal stenosis of the common bile duct and
      intrahepatic bile ducts, and pancreatic duct dilatation. At operation, a rock
      hard and nodular pancreas was noted. Cholecystectomy and Roux-en-Y
      hepaticojejunostomy, with an access loop, was successfully performed. Idiopathic
      fibrosing pancreatitis should be considered in young patients with obstructive
      jaundice, especially those affected with chronic inflammatory or autoimmune
      diseases. Glucocorticoid therapy would be the first-line treatment, although many
      patients require operation.

PMID- 18333267
TI  - Variation of a variation: case report of attenuated familial adenomatous
      polyposis.
AB  - BACKGROUND: First described in 1988, attenuated familial adenomatous polyposis
      (AFAP) is a rare autosomal dominant precancerous condition of the
      gastrointestinal tract. Few reports have described adenocarcinomatous change in
      the gastroduodenal region thus far. CASE OUTLINE: We report a case of AFAP
      presenting with extensive gastric polyposis and ampullary adenocarcinoma in
      absence of a positive family history of gastrointestinal cancer and a novel
      mutation.

PMID- 18333268
TI  - Left-sided gallbladder associated with congenital liver cyst.
AB  - BACKGROUND: A left-sided gallbladder is a rare congenital anomaly defined as a
      gallbladder attached to the lower surface of the left lateral segment of the
      liver, i.e. to the left of the interlobar fissure and round ligament. CASE
      OUTLINES: In two women aged 42 and 70 years a left-sided gallbladder was
      associated with a congenital cyst of the liver. In the first patient, the ectopic
      gallbladder was an incidental finding at operation for a symptomatic liver cyst;
      as the gallbladder was normal it was not removed. The second patient underwent
      operation for chronic calculous cholecystitis, when the left-sided gallbladder
      and congenital liver cyst were found. An operative cholangiogram was normal, the
      cystic duct joining the common bile duct from the right side. The gallbladder was
      removed, and the cyst was de-roofed. Both patients had an uneventful recovery and
      remain symptom-free at 12 and 9 years respectively. DISCUSSION: To the best of
      our knowledge, the association of these two congenital anomalies has not been
      described previously.

PMID- 18333269
TI  - What is the role of "live surgical demonstrations" at conferences?

PMID- 18333271
TI  - What affects mortality after the operative management of hepatic abscess?
AB  - BACKGROUND: Historically, the operative mortality associated with hepatic abscess
      was >50%. More recently, patients have been treated with percutaneous drainage;
      however, those failing conservative management are treated operatively. Our aim
      was to evaluate the outcome of operation for hepatic abscess in those failing
      conservative treatment or in those presenting as a surgical emergency. PATIENTS
      AND METHODS: This was a retrospective review of patients undergoing operation for
      hepatic abscess at the Mayo Clinic, Rochester, Minnesota from 1990 to 2003.
      RESULTS: Of 288 patients diagnosed with hepatic abscesses, 32 required operation.
      Percutaneous drainage was the initial treatment in 15 (47%). The remaining 17
      were initially managed with operation. Operative indication was septic shock
      (41%), failed nonoperative management (31%), and failure to make a diagnosis
      (28%). Operation was drainage (62%) or resection (38%). The morbidity and
      mortality rates were 41% and 15.6%, respectively. Factors associated with
      increased operative mortality were shock (p=0.04), INR > 1.5 (p=0.03), WBC >15
      000 (p=0.04), AST > 150 U/L (p=0.01), alkaline phosphatase >500 U/L (p=0.03),
      positive blood cultures (p=0.03), total bilirubin >2.0 mg/dl (p<0.01), multiple
      abscesses (p=0.01), and second operation (p<0.001). Factors not associated were
      extent of resection (p>0.10), peritonitis (p>0.10), intensive care admission
      (p>0.10), polymicrobial infection (p>0.10), and blood transfusion (p>0.10).
      CONCLUSION: Operative intervention is avoided in 89% of patients with hepatic
      abscess. Septic shock is the most common reason for operation. Patients with
      septic shock, INR>1.5, WBC>15 000, AST>150 U/L, total bilirubin >2.0 mg/dl,
      positive blood cultures, or alkaline phosphatase >500 U/L have increased
      mortality when undergoing operation for hepatic abscess.

PMID- 18333270
TI  - Liver failure following partial hepatectomy.
AB  - While major liver resections have become increasingly safe due to better
      understanding of anatomy and refinement of operative techniques, liver failure
      following partial hepatectomy still occurs from time to time and remains
      incompletely understood. Observationally, certain high-risk circumstances exist,
      namely, massive resection with small liver remnants, preexisting liver disease,
      and advancing age, where liver failure is more likely to happen. Upon review of
      available clinical and experimental studies, an interplay of factors such as
      impaired regeneration, oxidative stress, preferential triggering of apoptotic
      pathways, decreased oxygen availability, heightened energy-dependent metabolic
      demands, and energy-consuming inflammatory stimuli work to produce failing
      hepatocellular functions.

PMID- 18333272
TI  - Cryotherapy--a mature ablation technique.
AB  - This article discusses the use of cryotherapy for the treatment of hepatic
      tumours, from its early origins to the present day. Results of therapy,
      preoperative assessment, safety, and the pros and cons of its use are described.

PMID- 18333273
TI  - Piggyback technique in adult orthotopic liver transplantation: an analysis of
      1067 liver transplants at a single center.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) in adult patients has
      traditionally been performed using conventional caval reconstruction technique
      (CV) with veno-venous bypass. Recently, the piggyback technique (PB) without veno
      venous bypass has begun to be widely used. The aim of this study was to assess
      the effect of routine use of PB on OLTs in adult patients. PATIENTS AND METHODS:
      A retrospective analysis was undertaken of 1067 orthotopic cadaveric whole liver
      transplantations in adult patients treated between June 1994 and July 2001. PB
      was used as the routine procedure. Patient demographics, factors including cold
      ischemia time (CIT), warm ischemia time (WIT), operative time, transfusions,
      blood loss, and postoperative results were assessed. The effects of clinical
      factors on graft survival were assessed by univariate and multivariate
      analyses.In all, 918 transplantations (86%) were performed with PB. Blood
      transfusion, WIT, and usage of veno-venous bypass were less with PB. Seventy-five
      (8.3%) cases with PB had refractory ascites following OLT (p=NS). Five venous
      outflow stenosis cases (0.54%) with PB were noted (p=NS). The liver and renal
      function during the postoperative periods was similar. Overall 1-, 3-, and 5-year
      patient survival rates were 85%, 78%, and 72% with PB. Univariate analysis showed
      that cava reconstruction method, CIT, WIT, amount of transfusion, length of
      hospital stay, donor age, and tumor presence were significant factors influencing
      graft survival. Multivariate analysis further reinforced the fact that CIT, donor
      age, amount of transfusion, and hospital stay were prognostic factors for graft
      survival. CONCLUSIONS: PB can be performed safely in the majority of adult OLTs.
      Results of OLT with PB are as same as for CV. Liver function, renal function,
      morbidity, mortality, and patient and graft survival are similar to CV. However,
      amount of transfusion, WIT, and use of veno-venous bypass are less with PB.

PMID- 18333274
TI  - Clinical presentations and surgical management of liver hydatidosis: our 20 year
      experience.
AB  - BACKGROUND: Hydatidosis/echinococcosis of the liver is a very old problem in
      Greece and still exists, although it is declining. We have reviewed our 20 years'
      experience, and here we report the various clinical presentations of the disease
      and evaluate the clinical outcome of the surgical procedures performed. PATIENTS
      AND METHODS: We conducted a retrospective analysis of the past 20 years' medical
      records; 35 patients (males 34%, females 66%, mean age 58 years) were treated
      surgically. Results. The presenting symptoms or findings leading to the diagnosis
      of liver echinococcosis were jaundice (six cases, 17%), abdominal pain (five
      cases, 14%), gastrointestinal discomfort of the upper abdomen (e.g. nausea,
      vomiting, distention, anorexia) (two cases, 6%), acute pancreatitis (one case,
      3%) and portal hypertension (one case, 3%). The rest of the cases were diagnosed
      incidentally (20 cases, 57%). External drainage and cystectomy with omentoplasty
      was performed in 21 cases (60%) and pericystectomy in 14 cases (40%). The mean
      hospital stay was 16.8 days. Morbidity and mortality were 18% and 3%,
      respectively, with no statistically significant differences between the two
      surgical approaches. The recurrence rate averaged 3%. DISCUSSION: A high index of
      suspicion is recommended when variable clinical manifestations of the upper
      abdomen are present. Meeting all criteria for surgical treatment of hydatid
      disease, external drainage and cystectomy should be the standard surgical
      procedure. Pericystectomy could be used for peripherally located liver cysts that
      are only partially surrounded by parenchyma. Resection procedures are considered
      too radical for a benign disease. Appropriate randomized controlled studies are
      needed to establish the definite surgical management of liver hydatidosis,
      including modern techniques such as laparoscopy and transcutaneous puncture under
      US guidance (PAIR technique).

PMID- 18333275
TI  - Use of a collagen-sealing device in hepatic resection: a comparative analysis to
      standard resection technique.
AB  - BACKGROUND: Blood transfusion has been reported as an independent risk factor for
      poor outcome after liver resection in spite of its well known benefits.
      Refinements in parenchymal dissection have been pursued to reduce blood loss and
      transfusion. A collagen-sealing device (CSD) has recently been touted as an
      alternative technique that aids in blood conservation. We report the results of
      our initial series of patients undergoing a CSD-assisted resection and present a
      historical comparison. PATIENTS AND METHODS: Consecutive patients who were
      undergoing liver resection at a single tertiary cancer centre were enrolled in
      this study. The Ligasure Atlas device (Valleylab Inc., Division of Tyco
      Healthcare) was used for parenchymal division in the CSD group. Known blood
      conservation techniques (i.e. low central venous pressure, ultrasonic dissection,
      Pringle clamp) were standardized in both groups. Clinical and outcome variables
      including operative time, estimated blood loss and transfusion requirements were
      collected. All statistical analyses were performed with SAS version 8.2e.
      RESULTS: In all, 28 consecutive patients underwent CSD-assisted hepatic resection
      between October 2003 and September 2004. The control group included 188 patients
      treated between January 1991 and September 2003. In the CSD group, we observed a
      reduction in mean estimated blood loss (930 vs 1450 ml, p=0.002) and mean
      transfusion requirements (0.46 vs 1.19 units, p=0.002). There was no increase in
      operative time with the new instrument (326 vs 363 min, p=0.167). DISCUSSION: Use
      of a CSD has the potential to further reduce blood loss and transfusion
      requirements without increasing operative time.

PMID- 18333276
TI  - Giant hemangiomas of the liver: surgical strategies and technical aspects.
AB  - The incidence of hemangiomas is 2-7% in the general population. We evaluated more
      than 300 patients with hepatic hemangiomas. Surgical removal of hepatic
      hemangiomas was performed in 48 cases due to uncertain diagnosis (2 cases),
      intractable symptoms (26 cases), size increase (18 cases), and liver failure in 2
      cases that were treated by hepatic transplantation. In all, 26 patients underwent
      enucleation of hemangiomas or segmentectomies, while the remaining 20 patients
      underwent right lobectomies or left lateral segmentectomies. Blood transfusions
      were required in four cases (including two liver transplants); mean post
      resection hospital stay was 6.3 days. We observed no perioperative mortality and
      only two cases of major morbidity (bile leaks not requiring reoperation). Our
      experience confirms that, after adequate patient selection, surgical treatment of
      hepatic hemangiomas is a very effective therapeutic choice with no mortality and
      low morbidity.

PMID- 18333277
TI  - Treatment of post liver transplantation bile duct stricture with self-expandable
      metallic stent.
AB  - OBJECTIVE: The aim of this study is to report our experience using self
      expandable covered metallic stents (Wallstent) to treat different types of
      biliary strictures after orthotopic liver transplantation (OLT). PATIENTS AND
      METHODS: Between January 1999 and July 2004, 222 OLTs were performed with
      choledocho-choledochostomy (CC) bile duct reconstruction. An anastomotic biliary
      stricture was diagnosed and treated by endoscopic retrograde
      cholangiopancreatography (ERCP) or percutaneous procedures in 100 patients (45%).
      The group of 21 patients (mean age 57.0+/-5.6 years) that were eventually treated
      with a biliary Wallstent was studied retrospectively. RESULTS: Significant
      persistent proximal or anastomotic strictures were diagnosed in 4 and 17
      patients, respectively. A Wallstent was inserted by ERCP or through a
      percutaneous route in 18 and 3 patients, respectively. The mean interval between
      diagnosis and Wallstent insertion was 179.7+/-292.8 (0-1113) days. The mean total
      number of procedures required per patient was 7.4+/-5.5. The mean stent primary
      patency duration was 10.8+/-7.8 (0.9-25.1) months with a 24-month primary patency
      rate of 26% at a mean follow-up time of 37.8+/-17.2 months. A hepatico
      jejunostomy was performed in five patients (24%). Two patients (10%) underwent
      retransplantation for diffuse ischemic cholangitis or chronic rejection. The
      overall complication rate was 4%. CONCLUSION: Treatment of post-transplant
      biliary stenosis using a Wallstent is a valuable option for delaying or avoiding
      surgery in up to 70% of patients. Proximal stenosis can be treated in the same
      manner in selected patients with major comorbidities.

PMID- 18333278
TI  - Liver resection in octogenarians.
AB  - BACKGROUND: Liver resections are increasingly being performed safely in elderly
      patients. There are no present reports of the operative safety of liver resection
      in octogenarians who represents a rapidly increasing segment of the population.
      The purpose of this study was to analyse the results of liver resection in
      octogenarians over a 5 year period within a tertiary referral liver surgery unit.
      METHODS: Prospective data collection and analysis of octogenarians having liver
      resection between 1999 and 2004. Retrospective detailed case note analysis was
      performed to determine peri-operative mortality and morbidity. Comparison were
      made to other large series of liver resection in younger patient cohorts. The
      primary outcome measure was 30 day mortality and secondarily a detailed analysis
      of post-operative complications was performed. RESULTS: A total 15 octogenarians
      (median age 82) were identified from the database. There was 1 peri-operative
      mortality. The remaining patients were all alive at 1, 3 and 6 month follow-ups
      with a median follow-up of 18 months. The commonest indication for liver
      resection was metastatic colorectal cancer (n=1). The median operating time was
      142.5 minutes and 67% of patients (n=10) had portal clamping for a median of 21.5
      minutes. The median length of hospitalization was 12 days with an ICU stay of 1
      day, 27% (n=4) had major surgical complications. A further 20% (n=3) had
      exacerbations of pre-existing comorbidities. CONCLUSION: Liver resection can be
      performed safely in octogenarians within a tertiary referral unit. It has a low
      mortality and an acceptable level of morbidity in carefully selected
      octogenarians.

PMID- 18333279
TI  - Curative resection for left-sided pancreatic malignancy.
AB  - BACKGROUND: Surgical technique in pancreatic cancer has seen significant
      developments, but much of the knowledge refers to pancreatic head carcinoma.
      Reports on the management of tumours of the body and tail have been less
      frequent. Current knowledge teaches that adenocarcinomas of the body and tail of
      the pancreas have a worse prognosis. The aim of this study is to report the short
      and long-term outcome in 20 patients with left-sided pancreatic malignancy,
      where 'resection for cure' was done. PATIENTS AND METHODS: Retrospective study of
      demographic data, symptomatology, diagnostic methods, operative management,
      pathology report, postoperative morbidity and mortality. RESULTS: Postoperative
      complications were seen in 40% of patients. One patient died on day 5 from sepsis
      with multiple organ failure. Other complications were intra-abdominal bleeding,
      bleeding from the gastroentero-anastomosis, postoperative jaundice, pleural
      exudate, wound dehiscence and intra-abdominal abscess. The patients with ductal
      adenocarcinoma had a median survival of 14 months and a 5-year survival of 17%.
      The median survival for the whole group of patients was 17 months and the 5-year
      survival was 23%. One patient with malignant insulinoma and two patients with
      adenocarcinoma had a survival exceeding 5 years (98, 174 and 183 months,
      respectively). DISCUSSION: Selected patients with left-sided pancreatic
      adenocarcinoma may be operated on with results similar to pancreaticoduodenectomy
      (Whipple procedure) for cancer of the pancreatic head regarding postoperative
      morbidity and mortality as well as long-term survival. Thus, although left-sided
      pancreatic cancer generally appears at a more advanced stage, it seems true that
      treatment results are similar if radical excision can be achieved.

PMID- 18333280
TI  - Prognostic value of p27 kip1 expression in adenocarcinoma of the pancreatic head
      region.
AB  - BACKGROUND: p27(kip1) is a tumour suppressor gene, functioning as a cyclin
      dependent kinase inhibitor, and an independent prognostic factor in breast,
      colon, and prostate adenocarcinomas. Conflicting data are reported for
      adenocarcinoma of the pancreas. The aim of this study was to establish the
      prognostic value of p27(kip1) expression in adenocarcinoma of the pancreatic head
      region. PATIENTS AND METHODS: The study included 45 patients (male/female ratio
      2:1; mean age 59, range 38-82 years) with adenocarcinomas of the pancreatic head
      region: 24 - pancreatic head, 18 - periampullary and 3 - uncinate process. The
      patients underwent the Kausch-Whipple pancreatoduodenectomy (n=39), pylorus
      preserving pancreatoduodenectomy (n=5), or nearly total pancreatectomy (n=1).
      Eight patients received adjuvant chemotherapy postoperatively. Follow-up time
      ranged from 3 to 60 months. Tumours were staged according to the pTNM
      classification (UICC 1997). Immunohistochemistry was done on paraffin-embedded
      blocks from tumour sections. Quantitative determination of p27(kip1) expression
      was based on the proportion of p27(kip1) -positive cells (< 5% = negative).
      Survival analysis was carried out using the Kaplan-Meier method and Cox
      regression model. RESULTS: Positive p27(kip1) expression was detected in 22
      tumours (49%), whereas 23 tumours (51%) were p27(kip1)-negative. There were no
      significant correlations between p27(kip1) index and stage or lymph node
      involvement. Median survival time in patients with p27(kip1)-positive tumours was
      19 months, whereas in patients with p27(kip1)-negative tumours it was 18 months
      (p=0.53). A significant relationship was found between p27(kip1)-negative tumours
      and radical resection (p=0.04). Multivariate survival analysis revealed that the
      localization of the tumour (pancreatic head/uncinate process vs periampullary)
      was the only significant and independent prognosticator (p = 0.01, Cox regression
      model). Resection margins involvement and grade remained nearly significant
      prognostic factors (p=0.07 and p=0.09, respectively). CONCLUSION: We conclude
      that p27(kip1) has limited overall prognostic utility in resected carcinoma of
      the pancreatic head region, but its potential role as a marker of residual
      disease needs to be further assessed.

PMID- 18333281
TI  - Using faecal elastase-1 to screen for chronic pancreatitis in patients admitted
      with acute pancreatitis.
AB  - BACKGROUND: Patients presenting with acute pancreatitis may have co-existing
      chronic pancreatitis, the accurate diagnosis of which would potentially guide
      appropriate management. Gold standard tests are often invasive, costly or time
      consuming, but the faecal elastase-1 assay has been shown to be comparatively
      accurate for moderate and severe exocrine deficiency. This study aimed to
      evaluate fecal elastase-1 concentration [FE-1] against clinical criteria for
      chronicity in an acute setting. PATIENTS AND METHODS: [FE-1] was performed on
      patients admitted with acute onset of epigastric pain and a serum lipase at least
      three times the upper limit of normal. Clinical diagnosis of chronic pancreatitis
      was defined by the presence of specific clinical, pathological or radiological
      criteria. A [FE-1] value of <200 microg/g was similarly considered indicative of
      chronic exocrine insufficiency. Thus a 2 x 2 table comparing [FE-1] and clinical
      diagnosis was constructed. RESULTS: After exclusion of liquid stool specimens,
      105 stool specimens from 87 patients were suitable for [FE-1] determination. [FE
      1] was evaluated against the clinical diagnosis of chronic pancreatitis,
      initially for the whole sample, and then after exclusion of cases of moderate and
      severe acute pancreatitis (Ranson score >2). The latter analysis, based on an
      exocrine insufficiency threshold of 200 microg/g, yielded a sensitivity of 79.5%,
      specificity of 98.0%, positive predictive value of 96.9% and negative predictive
      value of 86.0%. CONCLUSION: [FE-1] is an accurate screening tool for underlying
      chronic exocrine insufficiency when taken in the course of a hospital admission
      for mild acute pancreatitis.

PMID- 18333282
TI  - Increased intra-abdominal pressure: is it of any consequence in severe acute
      pancreatitis?
AB  - BACKGROUND: Increased intra-abdominal pressure (IAP) is detrimental for the
      recovery of organ function in trauma and emergency patients. The aim of this
      study was to assess the correlation between the dynamics of IAP and organ
      dysfunction in severe acute pancreatitis (SAP). MATERIALS AND METHODS: Management
      of SAP between 2000 and 2004 was analysed. SAP was classified according to
      Atlanta 1992. Organ dysfunction, systemic inflammatory response syndrome (SIRS)
      and outcomes in relation to the IAP were assessed. IAP was measured indirectly.
      RESULTS: A total of 65 patients, with an average APACHE II score of 6.44,
      complied with the Atlanta criteria. In all, 34 patients received conservative
      treatment and 31 were operated. SIRS was observed in 59 cases and multiple organ
      dysfunction syndrome (MODS) in 61 cases. IAP was significantly higher in the 25
      most complicated patients requiring renal replacement therapy (RRT), compared
      with 40 patients without RRT, 31.72 vs 21.4 cm/H(2)O (p=0.037). IAP interrelated
      positively with SOFA score (r = + 0.371, p<0.01) and organs involved (r = +
      0.356, p<0.01), and negatively with platelet count and enterally provided volume
      (r = - 0.284, p<0.01; r = - 0.5, p<0.01, respectively). Overall mortality (9.2%)
      was associated with surgery and sustained increase of the IAP over 25 cm/H(2)O.
      Our data support the pathophysiological interrelation of elevated IAP and
      development of organ dysfunction. CONCLUSION: Development of organ dysfunction in
      SAP could be associated with increased IAP. Grade III increase of IAP should be
      considered as an indicator for revision of treatment modalities.

PMID- 18333283
TI  - Telerobotic-assisted laparoscopic spleen-preserving partial resection of the
      pancreatic tail for insulinoma.
AB  - Laparoscopic pancreatic resection is rarely described. Telerobotic-assisted
      laparoscopy may offer some advantages for resection of the pancreatic tail. A 49
      year-old woman was diagnosed with insulinoma located in the pancreatic tail.
      Telerobotic-assisted laparoscopic spleen-preserving resection of the pancreatic
      tail was performed. Operation time was 195 minutes. The postoperative course was
      uneventful. The previously described advantages of a telerobotic approach with
      extended range of motion and three-dimensional view make more complex operations
      like pancreatic resection possible and may offer extended indications for
      laparoscopic surgery.

PMID- 18333284
TI  - Delayed presentation of haemobilia after penetrating liver injury.

PMID- 18333285
TI  - 2006 AHBPA Meeting.

PMID- 18333286
TI  - Glial cell development and function in the Drosophila visual system.
AB  - In the developing nervous system, building a functional neuronal network relies
      on coordinating the formation, specification and survival to diverse neuronal and
      glial cell subtypes. The establishment of neuronal connections further depends on
      sequential neuron-neuron and neuron-glia interactions that regulate cell
      migration patterns and axon guidance. The visual system of Drosophila has a
      highly regular, retinotopic organization into reiterated interconnected synaptic
      circuits. It is therefore an excellent invertebrate model to investigate basic
      cellular strategies and molecular determinants regulating the different
      developmental processes that lead to network formation. Studies in the visual
      system have provided important insights into the mechanisms by which
      photoreceptor axons connect with their synaptic partners within the optic lobe.
      In this review, we highlight that this system is also well suited for uncovering
      general principles that underlie glial cell biology. We describe the glial cell
      subtypes in the visual system and discuss recent findings about their development
      and migration. Finally, we outline the pivotal roles of glial cells in mediating
      neural circuit assembly, boundary formation, neural proliferation and survival,
      as well as synaptic function.

PMID- 18333287
TI  - Progression of Kaposi sarcoma associated with iatrogenic Cushing syndrome in a
      person with HIV/AIDS.
AB  - This case report describes an exacerbation of AIDS-associated Kaposi sarcoma (KS)
      in the setting of iatrogenic Cushing syndrome caused by an interaction between
      ritonavir-boosted atazanavir and fluticasone. Discontinuation of fluticasone
      resulted in resolution of the cutaneous KS. Clinicians should be aware of this
      potential drug-drug interaction that can result in increased corticosteroid
      levels. Inhaled corticosteroids should be used cautiously in persons with
      HIV/AIDS who have a history of KS and are being treated with a boosted atazanavir
      regimen because this can potentially exacerbate KS.

PMID- 18333288
TI  - [A cold, confused and edematous 56-year old man].

PMID- 18333289
TI  - [Endocrinologic emergency medicine].

PMID- 18333290
TI  - [Still high mortality in Iraq].

PMID- 18333291
TI  - Reaching optimal iodine nutrition in pregnant and lactating women and young
      children: programmatic recommendations.

PMID- 18333292
TI  - VAC it - Some techniques on the application  of VAC dressings.

PMID- 18333293
TI  - Closure of the crural defect during a two-stage oesophagogastrectomy.

PMID- 18333294
TI  - The Wip1 phosphatase and Mdm2: cracking the "Wip" on p53 stability.
AB  - The p53 tumor suppressor is essential in maintaining genomic integrity in
      response to cellular stresses. In response to DNA damage, p53 is activated and
      stabilized largely through post-translational modifications, including
      phosphorylation by DNA damage responsive kinases such as ATM and ATR. Activated
      p53 transactivates a battery of genes that can mediate either cell cycle arrest
      or apoptosis. In those instances where p53 facilitates cell cycle arrest, a means
      to return the cell to a pre-stress state with low p53 levels is important. The E3
      ubiquitin ligase Mdm2 is one p53 transcriptional target that accumulates after
      damage and promotes p53 ubiquitination and degradation. Thus, p53 and Mdm2 form a
      critical negative feedback regulatory loop that helps to maintain appropriate p53
      levels in the presence or absence of stress. We propose here that Wip1 (Wildtype
      p53-Induced Phosphatase 1), also known as PPM1D, plays an important role in the
      p53-Mdm2 autoregulatory loop. We have recently shown that Wip1, also a p53 target
      gene, dephosphorylates Mdm2 at Ser395 (an ATM target site), resulting in
      stabilization of Mdm2, enhanced Mdm2-p53 binding, and enhanced ubiquitination of
      p53 by Mdm2. Thus, Wip1 facilitates Mdm2-mediated degradation of p53. The p53
      inhibitory role of Wip1 implicates it as a potential oncogene and indeed Wip1 is
      amplified and overexpressed in a number of human cancers. Wip1 may inhibit p53
      signaling by multiple mechanisms, but our data suggests that its largest effects
      are due to dephosphorylation of Mdm2.

PMID- 18333295
TI  - Use of a cork-screw femoral head extractor  for removal of a stuck intramedullary
      nail.

PMID- 18333296
TI  - Inserting peritoneal dialysis catheters without  special instruments.

PMID- 18333297
TI  - Iodide concentrations in matched maternal serum, cord serum, and amniotic fluid
      from preterm and term human pregnancies.
AB  - OBJECTIVES: To characterize the matched maternal and cord plasma and the amniotic
      fluid concentrations of iodide in preterm and term human pregnancies. METHODS:
      Specimens were collected at the delivery of 121 singleton pregnancies (92 at
      term, 29 preterm) with no pre-existing medical complications. Plasma unbound
      iodide concentrations were measured by the difference between the protein bound
      iodine and the total iodine measured spectrophotometrically. Total iodide was
      measured in amniotic fluid. RESULTS: Maternal plasma iodide concentrations were
      1.6 +/- 0.4 mcg/dL (mean +/- S.D.) for preterm deliveries and 1.5+/ -0.5 mcg/dL
      for term deliveries. Cord plasma iodide concentrations were 1.4 +/- 0.5 mcg/dL
      for preterm deliveries and 1.7 +/- 0.7 mcg/dL for term deliveries. Cord plasma
      iodide concentrations at birth correlated highly with maternal levels (p <
      0.001). The cord:maternal plasma iodide ratio for all pairs was 1.2+/- 0.7. The
      average cord:maternal plasma iodide ratio was not significantly different between
      the preterm (0.9+/- 0.4) and term (1.3+/- 0.8) deliveries. Amniotic fluid iodide
      concentrations did not correlate significantly with cord plasma concentrations.
      CONCLUSION: Cord plasma concentrations of iodide correlate with paired maternal
      levels, indicating that, unlike the rabbit and other species, the human conceptus
      does not highly concentrate iodide.

PMID- 18333298
TI  - Emergency care. As populations grow, stand-alone EDs rise.

PMID- 18333299
TI  - Payment. Hospitals wait and wait for Medicaid payments.

PMID- 18333300
TI  - FL: Are your fax machines 'secured' for privacy?: failure to 'secure' fax
      machines can be risky. Florida Dept. of Corrections v. Abrit, 2007 FLSC04-1747
      (10/18/07) So.2d-FL.

PMID- 18333301
TI  - Global concerns fast requiring local action!

PMID- 18333302
TI  - Inter-rater and intra-rater reliability of the Bahasa Melayu version of Rose
      Angina Questionnaire.
AB  - The objective of the study is to translate the Rose Questionnaire (RQ) into a
      Bahasa Melayu version and adapt it cross-culturally, and to measure its inter
      rater and intrarater reliability. This cross sectional study was conducted in the
      respondents' homes or workplaces in Kelantan, Malaysia. One hundred respondents
      aged 30 and above with different socio-demographic status were interviewed for
      face validity. For each inter-rater and intra-rater reliability, a sample of 150
      respondents was interviewed. Inter-rater and intra-rater reliabilities were
      assessed by Cohen's kappa. The overall inter-rater agreements by the five pair of
      interviewers at point one and two were 0.86, and intrarater reliability by the
      five interviewers on the seven-item questionnaire at poinone and two was 0.88, as
      measured by kappa coefficient. The translated Malay version of RQ demonstrated an
      almost perfect inter-rater and intra-rater reliability and further validation
      such as sensitivity and specificity analysis of this translated questionnaire is
      highly recommended.

PMID- 18333303
TI  - Perceived barriers to self-management in Malaysian women with breast cancer.
AB  - Naturalistic inquiry using focus group interviews was undertaken to explore
      experiences and perceived barriers to self management in women with breast
      cancer. The aim was to identify their perceived barriers to self management to
      aid the development of rehabilitation programmes. Successful programmes are
      strongly linked to patients' perceived needs. Four focus groups consisted of 39
      women, were purposively recruited. Women's needs within the three areas of
      medical, emotional and role management of breast cancer were explored. The main
      barriers were unavailability of information, inability to access services-and
      support, and socioeconomic-cultural issues (entrenched myths, low-socioeconomic
      status, and inadequate insurance-health legislative coverage). The findings
      provide the critically lacking 'expert-view' of survivors, who verified the
      importance of the medical, emotional and role management tasks, and highlighted
      barriers and structural solutions. With breast cancer becoming recognised as a
      form of chronic illness, this study is timely.

PMID- 18333304
TI  - Focus on disease management.

PMID- 18333306
TI  - Abstracts from the Congress on the First 100 Years of Psychiatry in Bosnia and
      Herzegovina, October 17-20, 2007, Sarajevo.

PMID- 18333305
TI  - 2-[(E)-(4-hydroxy-3-methoxybenzylidene)amino]-N-(2-methylphenyl)-4,5,6,7
      tetrahydro-1-benzothiophene-3-carboxamide.
AB  - The title compound, C24H24N2O3S, exhibits antifungal and antibacterial
      properties. The compound crystallizes with two molecules in the asymmetric unit,
      with one molecule exhibiting 'orientational disorder' in the crystal structure
      with respect to the cyclohexene ring. The o-toluidine groups in both molecules
      are noncoplanar with the respective cyclohexene-fused thiophene ring. In both
      molecules, there is an intramolecular N-H...N hydrogen bond forming a pseudo-six
      membered ring which locks the molecular conformation and eliminates
      conformational flexibility. The crystal structure is stabilized by O-H...O
      hydrogen bonds; both molecules in the asymmetric unit form independent chains,
      each such chain consisting of alternating 'ordered' and 'disordered' molecules in
      the crystal lattice.

PMID- 18333307
TI  - Notice of Duplicate Publication.

PMID- 18333308
TI  - Isis current bibliography of the history of science and its cultural influences,
      2007.

PMID- 18333309
TI  - Preface. Main health issues in the last decade.

PMID- 18333310
TI  - Preface. Life style and chronic diseases.

PMID- 18333311
TI  - Abstracts of the summer meeting of the British Association for
      Psychopharmacology. July 23-26, 2006. Oxford, United Kingdom.

PMID- 18333312
TI  - Apcon 2007. Abstracts of the 56th Annual Conference of the Indian Association of
      Pathology and Microbiology. November 26-29, 2007. Pgimer, Chandigarh, India.

PMID- 18333313
TI  - Abstracts of the 48th Annual Conference of the Indian Society of Gastroenterology
      in association with the Indian National Association for Study of the Liver and
      the Society of Gastrointestinal Endoscopy of India. November 15-18, 2007.
      Bangalore, India.

PMID- 18333314
TI  - Nimesulide is a selective COX-2 inhibitory, atypical non-steroidal anti
      inflammatory drug.
AB  - In this review it is shown that nimesulide, a selective cyclooxigenase-2 (COX-2)
      inhibitor, is different from other selective COX-2 inhibitors and classical non
      steroidal anti-inflammatory drugs (NSAIDs). The anti-inflammatory effect
      mechanism of nimesulide (inhibition of inflammatory mediators) is similar to
      other classic NSAIDs, but the protective effect of nimesulide on classic NSAID
      induced ulcers elucidates the difference between nimesulide and these other
      drugs. It is known that the selective COX-2 inhibitor nimesulide prevents NSAID
      induced ulcers, while celecoxib and rofecoxib, which are more selective to COX-2,
      failed to prevent these ulcers. Nimesulide produces gastro-protective effects via
      a completely different mechanism. In addition, while selective COX-2 inhibitors
      increase the risk for cardiovascular diseases, nimesulide does not exert
      significant cardiotoxicity. This data suggests that gastrointestinal side effects
      of classic NSAIDs cannot be related to the COX-1 inhibition alone and also
      suggest that nimesulide is an atypical NSAID, which is different from both non
      selective and selective COX-2 inhibitors.

PMID- 18333315
TI  - Abstracts of the 2008 Society of Interventional Radiology 33rd Annual Scientific
      Meeting. March 15-20, 2008. Washington, DC, USA.

PMID- 18333316
TI  - The river Avon water scheme.

PMID- 18333317
TI  - "The gift of love": nineteenth-century religion and lesbian passion.

PMID- 18333318
TI  - [The accused, the executioner, and crowds: the popular perception of the death
      penalty in Zaragoza, 1855-1915].

PMID- 18333319
TI  - City of thieves: Moldavanka, criminality, and respectability in prerevolutionary
      Odessa.

PMID- 18333320
TI  - [Splenic abscess: revision of 7 cases].

PMID- 18333321
TI  - [Electrode lead endocarditis in a cardiac resynchronization device. Surgical
      treatment using cardiopulmonary bypass].

PMID- 18333322
TI  - [Over the adaptation and importance of the scientific publications during the
      formation period: ethics or aesthetics?].

PMID- 18333323
TI  - [Disseminated infection due to Mycobacterium bovis alter intravesical
      instillation of BCG].

PMID- 18333324
TI  - [Heart failure due to infectious origin].

PMID- 18333325
TI  - [Status of adolescent drinking habits in Japan: results of the 1996, 2000 and
      2004 surveys].

PMID- 18333326
TI  - [Current concepts and morphological aspects of drug induced liver injury].
AB  - Currently, the following areas are in the focus of interest in hepatology: study
      of hepatic stem cells, mechanisms of fibrogenesis and cirrhosis development;
      mechanisms of the development of steatosis, steatohepatitis and NASH/NAFLD;
      rejection of liver transplants; diagnosis of autoimmune hepatitis, primary
      sclerosing cholangitis and primary biliary cirrhosis; diagnosis of
      hemochromatosis; the importance and relevance of grading and staging of chronic
      hepatitis. DILI (Drug Induced Liver Injury) is also in the focus of interest.
      DILI is important because the histology of DILI overlaps almost all areas of
      liver pathology unrelated to drug injury. Moreover, there is not unified approach
      to DILI diagnostic and references are almost solely case reports. The diagnosis
      of DILI is also complicated by lack of information on pharmacological anamnesis
      of patients, frequent combination of drugs with natural compounds and influence
      of environmental factors. DILI is a cause of 10% of acute hepatitis and 15 % of
      liver failures with subsequent transplantation. Hepatotoxicity is also one of the
      most important reasons for drug withdrawal. This review covers basic informations
      on classification of hepatotoxic drugs, on the system of liver biopsy assessment
      when DILI is suspected, and it is an overview of the main histologic pictures of
      liver biopsy with examples of the most important drugs and differential
      diagnosis.

PMID- 18333327
TI  - [ASCUS in atrophy].
AB  - AIM: The peak of incidence in cervical carcinoma precedes epithelial atrophy
      following menopause. Nevertheless, some carcinomas develop in the postmenopausal
      period. Atrophy, namely the partially developed, shares some cytomorphology
      features with SIL, especially if inflammatory changes, common in this period,
      interfere. Proliferation test is recognized and accepted as a tool to clear
      uncertain findings. However, it means a repetitive investigation. The study is
      focused on the possibility to reduce the proliferation test employment with the
      help of proliferation activity investigation on questionable cell groups.
      Material of the retrospective study comprised routine pap smears from 22
      patients. Twenty-one of them were perimenopausal and menopausal patients who had
      16 inconclusive results (ASCUS or ASC-US, ASC-H in one of both versions of
      Bethesda classifications, i.e. ASCUS in atrophy of any type), 4 SIL in atrophy
      followed by histology, and 1 atrophy with negative cytology finding. In addition,
      there was one case of H SIL in a younger patient without atrophy. Altogether, 60
      cytology findings were reviewed as many of the patients had repetitive
      cytologies. METHOD: As a minimum, three images with diagnostically important cell
      groups were archived in the LUCIA Net image archiving system (Laboratory Imaging,
      Prague). Subsequently, the smears were dismounted, destained and used for
      immunocytochemical reaction to test proliferation activity with the Ki-67 (MIB 1)
      antibody. The results were archived in the LUCIA Net system again. The evaluation
      of findings was done on a four-grade scale: 1) negative; 2) isolated
      positivities; 3) scattered positivities (less than 1/3 of cells in a cluster); 4)
      heavy disperse positivities (more than 1/3 of cells in a cluster). RESULTS: The
      procedure provided mostly a readable result. Archiving prior and following the
      immunocytochemistry procedure provided possibility of comparison of the
      polychrome stained smears and the MIB I tested. Patients with proven SIL
      exhibited the positivities in groups 2) to 4) (4/5). Rare scattered positivities
      /group 3/ were mostly (6x) found in compact groups with the appearance of
      immature metaplasia. The cytopathology findings eventually normalized in these
      patients. In patients with isolated MIB 1 positivities /group 2/ frequently (4/7)
      eventually normalized as well. Nevertheless, such minimal positivities were found
      also in two patients with a subsequently proven CIN. The MIB 1 positivities were
      variable even in the histopathology sections. The cytology features of the
      suspicious cell groups in slides obscured by inflammation were better visible
      following destaining for immunocytochemistry. Based on the results of our study
      we have developed an algorithm for employment of the proliferation activity test
      in the doubtful atrophy smears. We believe that it can be useful in the ASC-H in
      atrophy finding. Provided the positivities found are strong, a biopsy will be
      indicated. Medium and week positivities represent candidates for E-test and a 6
      months control.

PMID- 18333328
TI  - [What is your diagnosis: Answer: celiac disease--diagnostic type 3C lesion
      according to Marsh's classification].

PMID- 18333329
TI  - [Histopathological diagnosis of celiac disease in adults with functional
      dyspeptic syndrome].
AB  - Celiac disease is associated with permanent intolerance to gluten, which is found
      in some cereals. The symptoms of the disease are often nonconspicuous and the
      course of the disease is atypical. With the introduction of serological markers
      as a sensitive method of testing new cases of the disease were identified.
      Despite of the increased screening intensity among children and adults celiac
      disease in our region is still underdiagnosed. The article deals with the
      diagnostics of celiac disease in adults with functional dyspeptic syndrome. It is
      based on the laboratory and pathological correlation of 25 patients. Our aim was
      to identify the group at risk with functional dyspeptic syndrome and celiac
      disease. This disease can show symptoms from the onset all the way to relapse.
      Each person was examined by a gastroenterologist while hospitalized in the
      relevant department. In addition to the routine serological testing, blood
      samples were taken and sent for antiendomyzial antibody testing for positive
      reaction verification. A subsequent gastrointestinal examination was done and
      samples taken from the duodenum were sent for histology. Light microscopy
      analysis showed mucous damage typical for celiac disease, which is expressed with
      the levels of the Marsh histological grading. In closing, we recommend a three
      step approach to goal-oriented screening of celiac disease. Determination of
      autoantibody against tissue transglutaminase, if positive, then biopsy from the
      aboral duodenum, and consequently follow-up by testing for antiendomyzial
      antibody.

PMID- 18333330
TI  - [Primary synovial sarcoma of the kidney].
AB  - The authors present two cases of primary synovial sarcoma of the kidney. Both
      patients had a tumor mass in the kidney with vascular invasion of the inferior
      vena cava and right atrium of the heart in case no. 1. In case no. 2
      retroperitoneal lymph node metastasis and multiple metastases to both lungs were
      observed. Radical nephrectomies were performed in both patients. Histologically,
      the tumor in case no. 1 was monophasic and in case no. 2 poorly differentiated.
      Immunohistochemically, vimentin was diffusely positive and a few tumor cells were
      positive for epithelial membrane antigen. The tumor cells were negative for
      keratins, S- 100 protein, CD 34, smooth muscle actin, and desmin. In both cases,
      reverse transcription-polymerase chain reaction using ribonucleic acid extracted
      from formalin-fixed, paraffin-embedded tissues detected SYT-SSX 1 fusion gene
      transcripts, which are characteristic molecular findings of synovial sarcoma.

PMID- 18333331
TI  - [Rokitansky on atherosclerosis].
AB  - Karl Rokitansky (1804-1878) was the first to put forward a theory on pathogenesis
      of atherosclerosis. His "thrombogenic" theory is included in his famous three
      volume Manual of Pathological Anatomy. In its first edition issued in 1844 he
      describes the disease under the heading Excessive formation of plaques on the
      interior of vessels. He does not use the term "atherosclerosis", speaking simply
      about a process. The description is merely macroscopic, based predominantly on
      lesions of the aorta. The process starts as thickening--hypertrophy and plaque
      formation of the vascular inner layer. The apposed pseudomembrane is composed of
      foreign substance of blood origin--fibrin. The pseudomembrane eventually develops
      into either an atheromatous process or ossification. Rokitansky accurately
      describes an atheromatous plaque with its lipid-rich interior, including its
      complications, however, he misregards plaque calcification for ossification.
      Although Rokitansky is aware that the disease may cause both narrowing and
      dilatation of a vessel, he claims that outcomes of the disease are unknown. In
      the third edition of Rokitansky's textbook issued 12 years later there are
      already included histological drawings of the aortic intimal and medial lesions.

PMID- 18333340
TI  - [Management of diabetes in vulnerable populations].

PMID- 18333341
TI  - [Hypnosis and pain management].

PMID- 18333342
TI  - [Difficult wound healing].

PMID- 18333343
TI  - [Distinguishing between long healing wounds and complex wounds].

PMID- 18333344
TI  - [Evaluation and current treatments of burns and surgical wounds].

PMID- 18333345
TI  - [Evaluation and treatments of hard-to-heal venous leg ulcers].

PMID- 18333346
TI  - [Foot ulcers in the diabetic patient].

PMID- 18333347
TI  - [Arterial ulcers of the lower limbs].

PMID- 18333348
TI  - [Cancer wounds].

PMID- 18333349
TI  - [Towards a first national wound congress].

PMID- 18333350
TI  - [1/10. Nutrition, a public health priority].

PMID- 18333351
TI  - [10/10. Automated external defibrillation].

PMID- 18333352
TI  - [1/11. The patient with a total hip prosthesis].

PMID- 18333353
TI  - Current challenges of anticoagulant treatment.
AB  - Anticoagulant therapy plays an important role in current medical practice. The
      main types of anticoagulant agents are: heparins, hirudins and vitamin K
      antagonists. None of the drugs used as anticoagulants meet the criteria of an
      ideal anticoagulant because they have side effects and they interact with other
      compounds. The main side effect of anticoagulant therapy is bleeding. The choice
      of a certain anticoagulant is made by the doctor based on the clinical context
      and also on the desired effect.

PMID- 18333354
TI  - Management of pulmonary arterial hypertension associated with congenital heart
      disease.
AB  - Congenital heart diseases are the most common congenital malformations and
      account for about eight cases per 1000 births and are often associated with
      pulmonary arterial hypertension. Increased shear stress and the excess flow
      through the pulmonary vascular bed due to a systemic-to-pulmonary shunt lead to
      the development of pulmonary vascular disease and an increase in pulmonary
      vascular resistance. Without surgical repair approximately 30% of patients
      develop pulmonary vascular disease. Eisenmenger syndrome represents the extreme
      end of pulmonary arterial hypertension with congenital heart disease. We
      summarized the current therapeutic options for pulmonary arterial hypertension;
      conventional treatments including calcium channel blockers, anticoagulation,
      digitalis, diuretics, and new treatment: prostacyclin, bosentan, sildenafil,
      ambrisentan. Preliminary data of new therapies are encouraging with disease
      significantly improved natural history, but there is need for more evidence-based
      data.

PMID- 18333355
TI  - Cholesterol crystal embolism--new aspects of an "old" disease.
AB  - Cholesterol crystal embolism is increasing in frequency due, on the one hand to
      the aging of population and, on the other hand, to the great extent of invasive
      cardiovascular procedures, anticoagulant and thrombolytic therapy. Very often it
      has a protean symptomatology being considered as a "great masquerader". Due to
      its particular clinical picture it is sometimes misdiagnosed. This article
      presents the major clinical manifestations, the diagnostic strategy, the methods
      of prevention and treatment of this disease.

PMID- 18333356
TI  - Correlation between sTNFR-I and other negative prognostic factors in patients
      with chronic heart failure.
AB  - Tumor necrosis factor (TNF-alpha) and plasma levels of soluble tumor necrosis
      factor receptor I (sTNFR-I) are increased in patients with heart failure as an
      expression of chronic inflammation, representing a negative prognostic factor.
      Anemia and low serum lipid fraction are also negative prognostic factors, whose
      relationship with sTNFR-I has been less studied. METHODS: The study investigated
      54 patients with heart failure, 40 ischemic and 14 nonischemic, 35 males and 19
      females, aged 65 +/- 10 years. Plasma sTNFR-I values (nv < 3 pg/ml) and serum
      lipid fractions were determined in each patient and the prevalence of anemia (Ht
      < or = 41% in men; Ht < or = 38% in women) was established. Left ventricular
      ejection fraction (LVEF) was determined by using 2D echo. RESULTS: sTNFR-I was
      increased in patients with heart failure--222.79 +/- 97.08 pg/ml. Anemia was
      found in 40.74% of the patients, sTNFR-I being significantly increased in
      patients with anemia (242.82 +/- 49.12 pg/ml) compared to patients without anemia
      (194.9 +/- 117.3); p < 0.05. TChol (152.63 +/- 55.4 vs 177.81 +/- 38.52 mg%),
      LDLChol (101.47 +/- 42.4 vs 113.59 +/- 28.3 mg%) and TG (96.22 +/- 59.12 vs
      132.09 +/- 96.55 mg%) were insignificantly lower in patients with anemia.
      Patients with anemia and low LVEF did not present higher sTNFR-I values (236.548
      +/- 47.2) compared to patients with LVEF > 40% (245.75 +/- 52.1). A weak negative
      correlation r = -0.31 was noted between sTNFR-I and Ht in anemic patients and
      also between sTNFR-I and TChol (r = -0.31), LDLchol (r = -0.28), TG(r = -0.22).
      No correlation could be established between TChol, LDLchol, TG and Ht.
      CONCLUSION: In patients with heart failure, increased sTNFR-I as an expression of
      chronic inflammation is correlated with both anemia and low serum lipid fractions
      even if the exact nature of the relationship has yet to be established. There is
      no direct correlation between anemia and low serum lipid fractions.

PMID- 18333357
TI  - Apolipoproteins A-I and B-markers in coronary risk evaluation.
AB  - OBJECTIVES: To investigate if apoB, apoA-I and apoB/apoA-I ratios are independent
      risk factors for coronary heart disease and to determine their value in
      relationship with serum lipid fractions in evaluating the risk of coronary
      events. MATERIALS AND METHODS: We carried out a comparative observational study
      on 289 subjects divided into two groups: 144 subjects with old myocardial
      infarction, and 145 subjects without coronary heart disease, but with
      cardiovascular risk factors. None of the subjects received lipid-lowering drugs
      in the previous 3 months. RESULTS: The mean values of lipid fractions were lower
      in subjects with myocardial infarction than in subjects without coronary heart
      disease: total cholesterol (186.06 +/- 48.11 vs. 206.93 +/- 42.28 mg/dl, p =
      0.0001), LDL-cholesterol (118.57 +/- 42.95 vs. 129.53 +/- 39.75 mg/dl, p =
      0.023), HDL-cholesterol (43.64 +/- 12.32 vs. 50.48 +/- 21.09 mg/dl, p = 0.0008)
      and triglycerides (145.38 +/- 62.74 vs. 167.56 +/- 82.11 mg/dl, p = 0.01). The
      plasmatic levels of apoB were higher in subjects with myocardial infarction (1.12
      +/- 0.57 vs. 0.86 +/- 0.27 g/l, p = 0.0001), but the apoA-I was lower (1.31 +/-
      0.47 vs. 1.40 +/- 0.39 g/l, p = 0.101). The multivariate analysis indicated that
      plasmatic concentrations of apoB over 1.7 g/l are closely correlated with
      myocardial infarction (OR 3.96; 95% CI 2.87-5.02, p = 0.001) independent of other
      covariables such as age, smoking, diabetes, hypertension, lipid CT/HDL-C and the
      LDL-C/HDL-C ratio. The protective effect of apolipoprotein A1 against
      cardiovascular events after the adjustment for other cardiovascular risk factors
      (OR 0.72; 95% CI 0.57-0.83, p = 0.004) was also independent in multivariate
      analysis. CONCLUSION: These results highlight the significance of apoA-I and apoB
      in the evaluation of the cardiovascular risk. From this point of view, their
      predictive value is superior to that of serum lipid fractions. The data suggest
      that the determination of apoA-I and apoB is useful enough to be introduced in
      current clinical practice.

PMID- 18333358
TI  - Low prevalence of Helicobacter pylori infection in patients with gastric cancer.
AB  - The Helicobacter pylori (Hp) infection is a well-known carcinogenic factor. There
      are only limited data on the presence of Hp infection in gastric cancer in
      Romania. AIM: Cross-sectional study of the prevalence of Hp infection in gastric
      cancer. MATERIAL-METHODS: All cases of gastric cancer confirmed by gastroscopy in
      an endoscopy unit with national referrals were analysed. The Hp status was
      checked. The Hp + cases were studied compared with the Hp - cases. RESULTS: From
      6768 gastroscopies 84 cases with gastric cancer were detected. Among these in 40
      the Hp status was determined. 37 cases were carcinoma, 1 lymphoma, 2 cases
      without microscopical aspect of malignancy. In 8 cases (20%) Hp was found +. The
      majority of the patients with gastric cancer did not use PPIs. There were no
      demographic life style differences between the patients with gastric cancer who
      were Hp + and Hp -. CONCLUSION: Prevalence of the Hp infection in gastric cancer
      is lower than that reported in the literature. The investigation of Hp in gastric
      cancer should be done routinely. These data represent the starting point for a
      prospective study.

PMID- 18333359
TI  - Serological and histological correlations in celiac disease.
AB  - The aim of this study was to compare the sensitivity of the serological markers
      in patients with non-treated celiac disease by determination of antiendomysium
      and anti-tissue-transglutaminase autoantibodies separately and together. At the
      same time we examined the correlation between the serum levels of the two
      antibodies and the severity of the histological lesions. MATERIAL AND METHODS:
      The research included 26 persons (19 females, 7 males, age range 18-56 years) in
      whom the small bowel biopsy confirmed the villous atrophy. The sera of these
      patients were investigated by the determination of antiendomysium antibodies
      (AEA) and antitissue-transglutaminase antibodies (ATTG). For the morphological
      disorders we used the Marsh modified criteria. ATTG were determined by a sandwich
      ELISA technique and AEA were dosed by indirect immunofluorescence technique.
      RESULTS: 6 patients presented with partial villous atrophy (PVA), 7 with subtotal
      villous atrophy (SVA) and 13 with total villous atrophy (TVA). 23 persons were
      seropositive, having at least one of the two antibodies tested. The sensitivity
      of the serological investigation increased at 88% using both AEA and ATTG
      determinations. In patients with TVA, the sensitivity of ATTG was 100% and of AEA
      was 92%. In patients with SVA and PVA, the sensitivity of these antibodies was
      lower. Among the patients with SVA, 43% were negative for AEA and 50% for ATTG.
      The determination of AEA and ATTG together reduced the seronegativity at 15% in
      patients with SVA and at 34% in patients with PVA. CONCLUSIONS: Antitissue
      transglutaminase antibodies testing in patients with non-treated celiac disease
      is more sensitive than antiendomysium antibodies. The efficiency of the
      serological diagnosis improves when both AEA and ATTG are determined. Serum
      antibodies levels correlated very well with the severe histological alterations
      (TVA), but the correlation is not so good with SVA and PVA. So, we can tell that
      high levels of AEA and/or ATTG are suggestive for severe histological disorders
      in celiac disease.

PMID- 18333360
TI  - Serum magnesium in patients with acute ischemic stroke.
AB  - Magnesium (Mg) has important effects within the vascular system. Magnesium
      deficiency was shown to trigger vasoconstriction and enhance vascular endothelial
      injury, thus promoting the development and progression of atherosclerosis.
      However, it is still not completely understood whether low serum Mg also promotes
      the occurrence of stroke. We hereby intended to investigate Mg levels in serum in
      the early stage of ischemic stroke and to evaluate the relationship between serum
      Mg concentration and the development of neurological deficits. The study included
      forty patients with acute ischemic stroke (26 women and 14 men), mean age 56 +/-
      4 years, without any other serious injuries. Twenty-one healthy subjects, sex-
      and age-matched were selected as controls. The serum Mg concentrations were
      measured colorimetrically on a Hitachi 917 autoanalyzer. Serum levels of Mg were
      checked on admission, and at 48 hours after the onset of ischemic stroke. Using
      NIHSS, the neurological deficit was assessed on the 1st day, and 48 hours later.
      Statistical analysis was performed using the Student t test. The results confirm
      that there is a relationship between a low Mg concentration in serum at 48 hours
      after onset of ischemic stroke and the intensity of the neurological deficit.
      Mean value was 1.39 +/- 0.213 mmol/L (on admission), 1.47 +/- 0.181 mmol/L (at 48
      hours after the onset of stroke) versus 1.66 +/- 0.138 mmol/L (in controls).
      Severity of paresis degree was higher in the patients with low Mg levels (p <
      0.05). The serum Mg concentration has been suggested to possibly affect the
      neurologic state. A decrease in the serum Mg concentration indicates the severity
      of the injury. A magnesium substitution therapy may be useful.

PMID- 18333361
TI  - Pre-emption dimensional study aiming to obtain significant statistical results
      for the variation of serum cortisol during ovarian stimulation.
AB  - Ovarian stimulation has an important place in the contemporary impressive
      development of infertility treatment. There are few and not concordant data
      concerning its influence on cortisol serum levels. AIM: The present study aimed
      at finding the necessary number of determinations in order to statistically
      assess the variation of cortisol during and caused by the ovarian stimulation.
      METHODS: In 25 consecutive infertile women (23-45 years old, average: 32.4 years)
      enrolled in an ovarian stimulation program (gonadotropin releasing hormone
      agonist--busereline--from the first day of the cycle, human menopausal
      gonadotropin beginning with the 14th day of the cycle, ovulation triggering by
      human chorionic gonadotropin), serum cortisol was measured one month before the
      study, the 1st, 14th, 16th, 19th, 22nd, 24th day, the day before the triggering
      of the ovulation, one, two, 19 days and one month after triggering. General
      methods of data analysis map into descriptive and inferential statistics were
      used, with BMDP, SAS 6.0 and Epilnfo 5 software. RESULTS AND CONCLUSIONS: The
      calculated number of determinations, in order to obtain a significant statistical
      variation of cortisol for the studied set of samples and stimulation protocol is
      between 28-35--but smaller (15 and 19) around ovulation triggering and 39
      patients for a > or = 5% variation compared to control values. The suppositions
      considered in the present paper seem to offer a correct estimation for obtaining
      the size of the sample sets to be analyzed in a future study.

PMID- 18333362
TI  - Biophysics behavior of acupuncture points irradiated with low energy lasers.
AB  - This work describes the Low Energy Laser (LEL) coherent light interaction with
      the skin cover on acupuncture loci for the purpose of detecting and measuring the
      spatial and temporal alteration of the thermal, electric and optical properties
      of the LI4 (HEGU) acupoint, irradiated with a 685 nm, 30 mW, III.B Laser. Novel
      electrostatic imaging technique, an original Acupuncture 3-D Thermal and Electric
      Mapping Technique and an original Method for Laser-Skin Reflectance, were used in
      the study. The results indicate that the visible laser light, with low frequency
      and low power, specifically modify the 3-D pattern of the temperature, electric
      potential and electric impedance outline of an acupuncture point, meanwhile with
      a significant decrease of the laser reflectance index, all measured on a 27
      apparently healthy subject lot (48 years mean age, 54% male), when comparing with
      a non-active, non-acupunctural skin area, placed on the volar side of the same
      hand. The biophysical method presented, combines in a complex way and
      reproducible the electro stasis exploration (bioelectric homeostasis), with
      cutaneous thermodynamic exploration and photo-optical exploration of the derma
      and provides information that can be appreciated in dynamics and compared
      depending on the exploration target.

PMID- 18333363
TI  - The various phenotypes of diabetes and the endoplasmic reticulum of the beta
      cell.

PMID- 18333364
TI  - Difficulties in the management of an acute pericarditis (hospitalized after 5
      weeks of evolution).
AB  - Pericarditis is clinically heterogeneous, with acute, subacute or chronic
      manifestations, and within each subset, with variable intensity of symptoms, from
      asymptomatic to a highly symptomatic disease. The etiology is also heterogeneous,
      often without a suggestive symptomatology. Depending or not on the etiology,
      sometimes through immune mechanisms, there can be some important complications,
      like recurrent/chronic pericarditis, life threatening acute tamponade or
      disabling constrictive pericarditis. The prognosis is highly dependent on a
      correct and precocious diagnosis (etiology included) and therapy. When the
      initial response to therapy is inadequate, the management of chronic or recurrent
      pericarditis is very difficult and also very important, with failure often
      leading to pericardial constriction, a difficult to treat complication of
      pericarditis.

PMID- 18333365
TI  - Diabetes mellitus and Turner syndrome.
AB  - Noninsulindependent diabetes mellitus is 2-4 times more prevalent in Turner
      subjects as compared to normal females, and tends to develop at a younger age,
      but it is usually mild and responsive to weight loss or monotherapy. The primary
      pathogenic event is beta cell dysfunction, but insulin resistance also plays a
      central role and is worsened by the presence of hypertension, obesity and
      dyslipidemia which are common in Turner syndrome. We present the case of a 30
      year-old female patient with short stature, 141cm (<-- 2.5 SD), overweight 51kg,
      waist circumference 79cm, triangular facies, downslanting palpebral fissures, low
      set ears, short neck, secondary amenorrhea, palpitations, a history of polyuria,
      polydypsia of three months duration and a fasting morning glucose of 260 mg/dL.
      Cardiac and renal defects were excluded, hormonologic evaluation was consistent
      with hypergonadotropic hypogonadism (FSH 65 mUI/mL) and primary hypothyroidism
      (TSH 5.68 microUI/mL) and karyotype was 45,XO. She also had hypercholesterolemia
      (247 mg/dL), hypocalcemia (8 mg/dL), mild elevation of hepatic enzymes (ALAT 51
      U/L) and osteopenia (Tscore--2.22). Glycaemic control was achieved with diet
      only; therapy consisted of hormone replacement theraphy, thyroxine and beta
      blockers.

PMID- 18333366
TI  - IL-6 - STAT-3 - hepcidin: linking inflammation to the iron metabolism.
AB  - Recently discovered peptide hormone hepcidin is the key regulator of systemic
      iron homeostasis. Iron metabolism is regulated in response to variations in
      hepcidin plasma levels. Hepcidin levels that are inappropriately low or high
      result in iron overload or iron deficiency, respectively. The early studies
      showed that hypoxia, iron concentration, and inflammation influence hepcidin
      levels, but the exact mechanism remained elusive. Very recently, different
      research groups discovered that IL-6, through the Jak/STAT-3 signaling pathway,
      is involved in regulation of hepcidin levels in response to inflammatory stimuli.
      In this review we present a general view of hepcidin biology, with emphasis on
      regulation in inflammatory conditions.

PMID- 18333367
TI  - A modern, consequent and multilateral school of cardiology in the "N. Lupu"
      Institute of Internal Medicine.

PMID- 18333368
TI  - Pathogenic role of abnormal fatty acids and adipokines in the portal flow.
      Relevance for metabolic syndrome, hepatic steatosis and steatohepatitis.
AB  - Evidence has been provided that increased levels of non esterified fatty acids
      (NEFA) in the portal flow would produce insulin resistance and would also
      stimulate the hepatic protein synthesis, thereby explaining the increased plasma
      levels not only of apolipoprotein B, but also of other liver-derived enzymes and
      proteins occurring in overweight and hypertriglyceridemic patients. The high
      plasma concentration of triglyceride-rich lipoprotein would facilitate the
      transfer of cholesteryl esters from HDL and LDL to VLDL in exchange for
      triglycerides, a process mediated by liver-derived cholesteryl ester transfer
      protein (CETP). The triglyceride thereby acquired in HDL and LDL would then be
      hydrolyzed by hepatic lipase. The resulting association of increased
      triglycerides, low HDL cholesterol and small dense LDL is considered to be an
      atherogenic profile. The prothrombotic state, another feature of the metabolic
      syndrome, may also be explained by an enhanced hepatic synthesis of clotting
      factors and of the inhibitors of fibrinolysis. It was recently shown that
      adipocyte synthesized adiponectin reduces the release of fatty acids from the
      adipose tissue and would also enhance their uptake and oxidation in the muscle,
      thereby limiting their uptake in the liver. Decreased adiponectin production in
      obesity would therefore promote the development of insulin resistance, of
      atherogenic dyslipidemia and of the prothrombotic state. Because adiponectin also
      exerts an antiinflammatory activity by antagonizing TNFalpha, hypoadiponectinemia
      may be involved in atherogenesis and in the progression of hepatic steatosis to
      steatohepatitis.

PMID- 18333369
TI  - Hyperhomocysteinemia: clinical and therapeutical involvement in venous
      thrombosis.
AB  - Hyperhomocysteinemia, considered "the cholesterol of nineties", is an established
      risk factor for cardiovascular diseases and premature atherosclerosis.
      Hyperhomocysteinemia is due to genetic and acquired factors (unhealthy lifestyle
      with poor diet in folate and vitamin B, elderly, renal impairment, thyroid
      diseases, malignancies). More recently, hyperhomocysteinemia was associated with
      venous thrombosis. Several studies found a correlation with a usual site of
      thrombosis (central retinal vein, mesenterical level, cerebral veins, Budd-Chiari
      syndrome). Other studies showed the association between hyperhomocysteinemia and
      recurrent venous thrombosis. This condition is of high interest because
      homocysteine may represent a potentially reversible cause of thrombophilia.
      Although methylenetetrahydrofolate reductase (MTHFR) C677T genotype and deficits
      of folic acid, vitamin B12 lead to hyperhomocysteinemia, in cases with a
      thrombotic event the correlations between homocysteine level and folic acid as
      well as between homocysteinemia and vitamin B12 were found to be weak and no
      significant correlation between homocysteinemia and MTHFR was identified.
      Recently, some authors reported an independent association between low levels of
      folic acid or vitamin B12 and venous thrombosis. Regarding the MTHFR genotype,
      the risk for venous thrombosis is increased only in patients with factor V
      Leiden. A recent meta-analysis of 24 retrospective and 3 prospective studies
      published in electronic literature showed that a 5 micromol/L higher homocysteine
      level was associated with a 27% (95% CI: 1-59) higher risk of venous thrombosis
      in prospective studies and a 60% (95% CI: 10-134) higher risk in retrospective
      studies. A meta-analysis of the short-term trials of therapy with folic acid
      showed a reduction of 25% of homocysteinemia and a further reduction of 7% when
      vitamin B12 was associated. This situation may be associated with a 10% to 20%
      decreased risk of venous thrombosis. Further trials are required to estimate if
      this is worthwhile from the clinical point of view. In medical practice the
      measurement of homocysteinemia may be indicated in unexplained idiopathic venous
      thrombosis, or recurrent episodes or venous thrombosis occurred at an early age
      or at an uncommon site.

PMID- 18333370
TI  - Impact of obesity and omega-3 polyunsaturated fatty acids on fibrogenesis and
      responsiveness to antiviral therapy in chronic hepatitis C.
AB  - Chronic Hepatitis C (CHC) and obesity inflict significant health and economic
      burdens on the world. A complex interplay between these conditions results in the
      ultimate phenotype of liver disease. Taking into consideration the increasing
      prevalence of obesity in patients with CHC and the decreasing rate of sustained
      virologic response (SVR), it would be advantageous to identify potential
      therapeutic strategy to improve liver histology and responsiveness to antiviral
      therapy. The adipokines-leptin, adiponectin, TNF-alpha-, which are modified in
      obesity, have been proposed as determinant factors of non-responsiveness to the
      IFN-alpha/Ribavirin treatment and of liver fibrosis extension in patients with
      CHC and obesity. Weight loss and long-term maintenance of optimal weight resulted
      in a sustained improvement in hepatic fibrosis and an increased rate of SVR in
      obese patients with CHC. The ability to exert antiviral activities and the anti
      obesity effect of omega-3 PUFA provide a good basis for clinical use of these
      very interesting nutrients, both as dietary components and as future drugs with
      potentially beneficial effects and few side effects. We reviewed the mechanisms
      underlying the correlation of obesity with the nonresponsiveness to antiviral
      therapy and with fibrosis extension in CHC, and the mechanisms by which PUFA
      omega-3 may be associated with an increased efficacy of interferon-based
      therapies and an antifibrogenic effect in obese individuals with CHC.

PMID- 18333371
TI  - Comparison between heart rate variability and recovery in ischemic patients.
AB  - Both heart variability (HRV) and heart rate recovery (HRR) after exercise are
      considered to reflect the sympathetic-vagal balance and low values of them have
      negative prognostic significance, especially in ischemic patients. The main goal
      of the research was to establish if there is a correlation between HRR and HRV in
      ischemic patients and if interchangeability between them is possible. There were
      studied 63 patients with ischemic heart disease: old myocardial infarction,
      stable angina. unstable angina and silent ischemia. All patients performed
      exercise stress testing, the heart rate recovery being calculated as the
      difference between peak heart rate and the rate determined at one minute after
      the exercise was stopped. The "time-domain" HRV parameters SDANN, SDNN, RMSSD
      were automatically calculated during a 24 hours Holter ECG monitoring. The mean
      values were HRR: 39.24 +/- 17.47 beats/min (abnormal in 6% of the patients); HRV:
      SDNN-112.75 +/- 37.87 msec, SDANN-103.02 +/- 33.25 msec, RMSSD-50.21 +/- 48.15
      msec (low HRV in 68.3% of the patients). There was no significant correlation
      between HRR and HRV's parameters (p > 0.05). There was no significant difference
      between HRR's mean in subjects with normal or abnormal values of HRV parameters
      (p > 0.05). Thus, in our study, the HRV values cannot be predicted by the
      determination of HRR, HRV parameters being more sensible than HRR to reveal
      increased sympathetic drive.

PMID- 18333372
TI  - Hypothyroidism in Turner syndrome.
AB  - Turner syndrome (TS) is characterized by an increased prevalence of
      hypothyroidism, the main etiology being autoimmunity. The aim of our study was to
      assess the prevalence of hypothyroidism in patients with Turner syndrome, to
      analyze the correlations with clinical, chromosomal, hormonal and metabolic
      features and to compare hypothyroid with euthyroid Turner subjects. We studied 28
      patients with TS (mean age 24.68 +/- 9.59yr). 78.57% with 45,XO. 10.71% with
      45,XO/46,XX and 10.71% with other karyotypes. Hypothyroidism was diagnosed in 10
      patients (35.7%). TSH level was positively correlated with thyroid autoantibodies
      titer (p < 0.001), maternal age at conception (p< 0.01), the presence of
      spontaneous puberty (p < 0.05) and relative height (p < 0.05), and negatively
      correlated with FSH level (p < 0.001) which is an indicator of the estrogenic
      status, and was not correlated to karyotype. Hypothyroid Turner subjects had
      higher relative heights (p < 0.05) and lower FSH levels (p < 0.05) than euthyroid
      subjects, but cholesterol levels and BMI were not significantly different.

PMID- 18333373
TI  - Platelet activation in patients with systemic scleroderma--pattern and
      significance.
AB  - The vasooclusive features of scleroderma are attributed to the vessel wall
      anomalies, while platelet's intervention is less studied. AIM: platelet
      activation markers (PAM) pattern and significance in systemic sclerosis. DESIGN:
      20 scleroderma patients with severe Raynaud phenomenon, under aspirin treatment,
      were evaluated by quantitative flow-cytometry for PAM (P-selectin, GPIIbIIIa,
      CD40L) in correlation with scleroderma activity and severity, systemic
      endothelial dysfunction (flow-mediated vasodilatation), systemic inflammation
      (serum CRP and IL-6) and cold-provocation test. Associated autoantibodies (ANCA,
      antiTPO, anticardiolipin, antiplatelet, antimitochondrial antibodies) were
      evaluated in relation to IL-6. RESULTS: PAM were expressed in 11 (55%) cases: P
      selectin in 5 (45.45%), GPIIbIIIa in 1 (9.1%), combined P-selectin and GPIIbIIIa
      in 5 (45.45%), CD40L in 0 cases. Scleroderma patients expressing PAM had
      increased incidence of disease activity and severity. There was no correlation
      between PAM and systemic endothelial dysfunction. CRP increased in 14(70%) cases
      was correlated with P-selectin and GPIIbIIIa expression (r = 0.28). Normal IL6
      present in 19 (90.9%) cases was correlated with lack of CD40L expression (r =
      0.69) and with low autoantibodies incidence (r = 0.69 for ANCA, 0.55 for anti TPO
      and antiplatelet, 0.39 for anti cardiolipin, 0.45 for antimitochondrial). After
      cold provocation test PAM were significantly lost and were not expressed de novo.
      CONCLUSIONS: In systemic scleroderma platelet activation markers are correlated
      with disease activity and severity and increased CRP and are not correlated with
      systemic endothelial dysfunction or exposure to cold. Normal IL-6 was correlated
      with lack of CD40L expression and with low incidence of associated
      autoantibodies.

PMID- 18333374
TI  - Integrin expression on monocytes and lymphocytes in unstable angina short term
      effects of atorvastatin.
AB  - Inflammatory reactions in coronary plaques play an important role in the
      pathogenesis of acute atherothrombotic events. The most powerful class of lipid
      lowering drugs available-statins (3-hydroxy-3-methylglutaryl coenzyme A reductase
      inhibitors)--have additional actions, unrelated to cholesterol reduction,
      including anti-inflammatory and immunomodulatory properties. This study sought to
      determine if atorvastatin affects monocyte and lymphocyte activation in patients
      with unstable angina and mild primary hypercholesterolemia. Following a 4-weeks
      hypolipemiant-free baseline period, 22 patients-12 with unstable angina (UA) and
      10 patients with stable coronary heart disease (SCHD) - were treated with
      Atorvastatin 20 mg/day. Lipopolysaccharide (LPS)-receptor (CD14) and HLA-DR
      expression on monocytes and beta-integrins (CD11b, 11c, 49d) on monocytes and
      lymphocytes were measured by flow cytometry before and after treatment with
      atorvastatin for 8 weeks. Monocyte CD11b, 11c and CD14 expression and T
      lymphocytes CD11b expression were significantly (p < 0.001) higher in UA patients
      before treatment when compared with that in SCHD patients. In patients with UA,
      they decreased markedly with atorvastatin treatment. The reduction in expression
      of adhesion molecule on monocytes and lymphocytes and the concentrations of CRP
      and sICAM-1 may crucially contribute to the clinical benefit of atorvastatin in
      coronary artery disease, independent of cholesterol lowering effects.

PMID- 18333375
TI  - Evaluation of antiphospholipid antibodies in young women with ischemic stroke.
AB  - There is an association between antiphospholipid antibodies (aPL) and ischemic
      stroke. The detection of aPL in young women is to characterize a subset of
      patients with venous or/and arterial thrombotic complications, to describe
      whether aPL are a cause, a consequence, or an accompanying event. Cerebral
      ischemia is the most common arterial thrombotic manifestation associated with the
      presence of aPL. In patients with ischemic stroke, diagnostic value of aPL can be
      increased by patient testing for antibodies against cardiolipin. The aim of the
      study was to assess the prevalence of IgG-aCL in young women with ischemic
      stroke. IgG-aCL were screened by ELISA in 34 young women, under the age of 45
      (mean age 36.7 years) with ischemic stroke without the common stroke risk
      factors: hypertension, diabetes, hyperlipidemia, vasculitis or arterial
      fibrillation, smoking. Other 20 healthy, age and sex matched adults with no
      evidence of disease were also included as a control group. Twelve of the 34 (35%)
      patients were found to have aCL of the IgG isotype. The present study confirmed
      that IgG-aCL may be associated with ischemic stroke; this phenomenon is however
      relevant only in a small subgroup of young women. They should be sought in all
      stroke patients under the age of 45, especially those with previous histories of
      deep venous thrombosis, spontaneous abortion or thrombocytopenia.

PMID- 18333376
TI  - Evaluation of glycemic control of type II diabetes mellitus treated only with
      diet.
AB  - Assays of HbA1c, after few years or months from the registration of new diagnosed
      type II diabetes mellitus, provide interesting information about the balance of
      glycaemic control. In a very high percentage, the value of HbAlc needs to be
      treated. It is imperative to introduce a new program in treating more
      aggressively the diabetes from the beginning, to reach the target and maintain
      the glycaemic control at this level for as long time as possible.

PMID- 18333377
TI  - Could constitute saliva the first line of defence against oxidative stress?
AB  - The oral cavity, a very complex and unique milieu due to its dual function,
      respiratory and digestive, is the only place in the body where the mineralized
      tissue is exposed to the external environment. In this environment there are
      complex interactions between various surfaces: host soft and hard tissues, food,
      air and microorganisms. Saliva is in the middle of this environment and tries to
      cope with an ever-changing milieu. It includes a large number of inorganic and
      organic compounds, which act as a "mirror of the body's health". In addition to
      its other functions, saliva could constitute the first line of defence against
      oxidative stress. The body contains a number of protective antioxidant
      mechanisms. Saliva is also rich in antioxidants. We review the current available
      data and from our laboratory concerning antioxidant capacity of saliva.
      Substantial data are available in literature on the role of reactive oxygen
      species and antioxidants in diseases, but few information is available on oral
      pathology. Due to its composition and functions, saliva could have a significant
      role in controlling and/or modulating oxidative damages in the oral cavity.

PMID- 18333378
TI  - A clinical approach in regression of glomerulosclerosis.
AB  - The role of the renin angiotensin system (RAS) in hypertension and end organ
      damage has long been recognized. Angiotensin 1 converting enzyme inhibitors
      (ACEI) are superior to other antihypertensive agents in protecting the kidney
      against progressive deterioration, even in normotensive persons. Like ACEI,
      angiotensin II type 1 receptor antagonists (AT1RA) ameliorate or even reverse
      glomerulosclerosis in rat animal models. These findings suggest that Angiotensin
      II (Ang II) has nonhemodynamic effects in progressive renal disease. The RAS is
      now recognized to be linked to induction of plasminogen activator-inhibitor-1
      (PAI-1), possibly via the AT4 receptor, thus promoting both thrombosis and
      fibrosis. Interactions of the RAS with aldosterone and bradykinin may have an
      impact on both blood pressure and tissue injury. The beneficial effect on renal
      fibrosis of inhibiting the RAS likely reflects the central role that angiotensin
      has in regulating renal function and structure by its various actions. This
      article explores the interaction of the renin angiotensin aldosterone system with
      PAI-1, and the potential significance of these interactions in the pathogenesis
      of progressive renal disease and remodeling of renal sclerosis.

PMID- 18333379
TI  - [Mechanical ventilation: learning from neonates].

PMID- 18333380
TI  - [Monitoring airway pressure in pediatric anesthesia: an experimental model of
      intratracheal medication and pressure-volume loops].
AB  - BACKGROUND: In the monitoring of anesthesia, airway pressure is measured in the
      ventilator or at the closest possible connection to the endotracheal tube.
      OBJECTIVE: To compare the airway pressures and pressure-volume loops obtained
      before connection to the endotracheal tube with those obtained in the trachea.
      MATERIAL AND METHODS: We carried out a single-blind prospective observational
      study on ASA 1 patients between the ages of 7 and 12 years ventilated in volume
      control mode with an inspiration-to-expiration ratio of 1:2. Intratracheal and
      extratracheal peak and plateau pressures and pressure-volume loops were recorded.
      A special device was designed to monitor intratracheal pressure. Both sensors
      were connected to the same spirometric analysis system. The variables were
      measured on intubation and 5, 10, 15, 20, 30, 40, 50, and 60 minutes after
      intubation. The recorded pressures were compared using the t test, the Pearson
      product moment correlation coefficient (r), and the Spearman rank correlation
      coefficient (p), and regression models were fit to the data. RESULTS: Seventy-one
      patients were enrolled. The mean (SD) pressure difference between the 2 systems
      was 3.5 (0.35) cm H2O (P < .01) and no differences between the endotracheal peak
      pressures and the plateau pressures were observed. The intratracheal areas of the
      pressure-volume loops were 15% lower than the extratracheal areas. The value of r
      for the correlation between the intratracheal peak and plateau pressures was
      0.998 (P < .01). The value of r for the correlation between the intratracheal and
      extratracheal peak pressures was 0.981 (P < .01). Analysis of variance confirmed
      the linear relationship. CONCLUSIONS: The difference between the intratracheal
      and extratracheal pressure measurements is due to the different locations at
      which the measurements are taken.

PMID- 18333381
TI  - [Monitoring airway gas in pediatric anesthesia: an experimental model for
      endotracheal gas measurement].
AB  - BACKGROUND: We designed an endotracheal probe for measuring inspired and expired
      gas fractions during pediatric general anesthesia. OBJECTIVE: To compare the gas
      fractions measured by means of intratracheal and extratracheal monitoring.
      MATERIAL AND METHODS: The study included ASA 1 patients between the ages of 7 and
      12 years under inhaled anesthesia with mechanical ventilation. The following
      parameters were recorded inside and outside the trachea: inspired and expired
      oxygen, nitric oxide (N2O) and sevoflurane fractions; the expired and inspired
      fraction gradients; PaCO2; and end-tidal carbon dioxide (ETCO2). Measurements
      were taken by an airflow sensor (Pedi-Lite) in the circuit before the point of
      connection to the endotracheal tube and by an intratracheal probe placed between
      the tube and the carina. Both sensors were connected to the same monitor.
      Measurements were taken on intubation and 5, 10, 15, 20, 30, 40, 50, and 60
      minutes thereafter. PaCO2 was recorded at the same time. The recorded values were
      analyzed using the t test and the Pearson product moment correlation coefficient
      (r), and regression models were constructed using analysis of variance. RESULTS:
      Seventy-one patients were enrolled in the study. The mean difference (SD) ETCO2
      was 5 (3) mm Hg higher according to endotracheal measurement (P < .005), and that
      measurement was almost identical (+/-13 mm Hg) to the PaCO2 (P < or = .5). The
      inspired/expired gradients of endotracheal measurement of oxygen and N2O were 3
      (2) points higher (P < .05) than the gradients of extratracheal measurements. In
      the case of sevoflurane gradients, however, the extratracheal values were higher
      (mean difference, 0.6 [0.2] points, P < .05). The inspired/expired oxygen and N2O
      gradients became equal after 18 (3) minutes; the sevoflurane gradients became
      equal after 8 (2) minutes. CONCLUSIONS: Intratracheal and extratracheal
      measurements of the inspired and expired fractions of mixed gases provide
      different results.

PMID- 18333382
TI  - [Experience with uterine artery embolization in the treatment of massive
      postpartum hemorrhage].
AB  - OBJECTIVE: To analyze our experience with uterine artery embolization in the
      management of massive hemorrhage in obstetric patients. PATIENTS AND METHODS:
      This observational, retrospective study analyzed all deliveries requiring a blood
      transfusion that were performed in the maternity unit of Hospital Universitario
      La Paz between January 1, 2000 and December 31, 2005. RESULTS: A total of 57,835
      deliveries were performed with an incidence of postpartum hemorrhage of 0.7% (406
      episodes). Uterine artery embolization was performed on 51 patients and 45
      patients underwent obstetric hysterectomy. Both procedures were performed on 11
      patients. Ten of the patients who underwent obstetric hysterectomy subsequently
      required uterine artery embolization, whereas only 1 patient required an
      obstetric hysterectomy following embolization because the hemorrhage was not
      resolved. The mean consumption of blood products for patients who underwent
      obstetric hysterectomy was twice that for patients who underwent uterine artery
      embolization. There were no complications secondary to embolization. CONCLUSIONS:
      Uterine artery embolization is a safe and effective procedure for managing
      massive postpartum hemorrhage.

PMID- 18333383
TI  - [Electrophysiological effects of sevoflurane in comparison with propofol in
      children with Wolff-Parkinson-White syndrome].
AB  - OBJECTIVE: To evaluate the electrophysiological effects of sevoflurane in
      children with Wolff-Parkinson-White (WPW) syndrome undergoing radiofrequency
      ablation. METHODS: We performed a prospective study of 15 patients with WPW
      syndrome who were scheduled for an electrophysiological study (EPS) and
      radiofrequency ablation. Anesthesia was induced with fentanyl (2 microg/kg),
      propofol (3 mg/kg), and vecuronium (0.1 mg/kg), and initially maintained using
      propofol (100 microg/kg), with bolus administration of fentanyl and vecuronium as
      required. Four intracardiac catheters were introduced for the EPSpropofol, which
      included measurements of sinus-node function, sinoatrial-node conduction,
      refractory periods (atrial, AV-node, accessory pathway anterograde and
      retrograde, and ventricular), and the characteristics of induced orthodromic
      tachycardia. The propofol was then replaced with sevoflurane (1 MAC adjusted for
      age) and the measurements were repeated (EPSsevoflurane). The EPSpropofol and
      EPSsevoflurane data were compared using the Wilcoxon signed-rank test. RESULTS:
      The mean (SD) age was 9.3 (6) years. After administration of sevoflurane, the
      duration of the antegrade effective refractory period of the accessory pathway
      increased (EPSpropofol, 283 (22) ms; EPSsevoflurane, 298 (25) ms; P = .004), as
      did the duration of the minimum pacing cycle with 1:1 atrioventricular conduction
      (EPSpropofol, 244 (41) ms; EPSsevoflurane, 273 (28) ms; P = .028). No significant
      changes were observed in the other parameters. Ablation of the accessory pathway
      was achieved in all patients. CONCLUSIONS: Sevoflurane partially modified the
      properties of the accessory pathway but did not prevent ablation.

PMID- 18333384
TI  - [Is morphine still the analgesic of choice in acute myocardial infarction?].
AB  - Chest pain is the most common symptom of patients who present with ischemic heart
      disease. Morphine has traditionally been the drug of choice for managing chest
      pain in acute coronary syndrome (ACS) due to its high analgesic potency, though
      its physiological effects are poorly understood. Routinely used for managing
      chest pain, morphine is recommended in the 2002 guidelines of the American
      College of Cardiology/American Heart Association. This recommendation, however,
      is not based on a high level of scientific evidence but on expert opinion.
      Studies have found both for and against the use of morphine in ACS, suggesting
      that its benefits are perhaps not altogether clear. This review examines the
      pathophysiological effects of morphine and their cardiac implications, with
      special attention to a possible negative effect on ACS. We reviewed articles in
      the MEDLINE database from 1982 to 2006.

PMID- 18333385
TI  - [Acute opiate tolerance and postoperative hyperalgesia after a brief infusion of
      remifentanil managed with multimodal analgesia].
AB  - Postoperative analgesia may be complicated by the occurrence of acute opiate
      tolerance and hyperalgesia. We present the case of a patient who underwent
      gynecological surgery that was complicated by intense pain in the immediate
      postoperative period. The pain was attributed to the development of acute opiate
      tolerance caused by the brief infusion of a high dose of remifentanil. The opiate
      tolerance was complicated by tactile hyperalgesia at the site of the surgical
      wound. Pain management with the usual dose of nonsteroidal anti-inflammatory
      drugs associated with a high dose of morphine (50 mg administered in less than 2
      hours) produced no analgesic or adverse effects. The pain was finally brought
      under control by epidural perfusion of ropivacaine and fentanyl and subsequently
      maintained with multimodal analgesia.

PMID- 18333386
TI  - [Continuous infusion of baclofen and an antibiotic for treating meningitis
      related to refilling of an intrathecal infusion pump reservoir].
AB  - Baclofen via intrathecal infusion pump is a widely used treatment severe
      spasticity. Complications are rare and usually mild, though they can also be
      serious. The sudden discontinuation of intrathecal baclofen may have significant
      adverse effects. We report the case of a 59-year-old man with chronic spasticity
      and torsion dystonia who developed meningitis due to Staphylococcus epidermidis
      due to contamination of the intrathecal, infusion pump reservoir during
      refilling. It was decided to treat the patient by administering vancomycin
      through the pump, together with the baclofen. We believe that changing the
      intrathecal perfusion pump is not necessary as the first measure to take in these
      cases. Combined infusion of baclofen and an antibiotic through the pump makes it
      possible to maintain antispastic treatment, sterilize the pump reservoir and
      tubes, and effectively treat infections that develop during use of these systems.

PMID- 18333387
TI  - [Acute coronary syndrome during a cesarean section in a healthy young woman].
AB  - Acute coronary syndrome (ACS) during pregnancy and delivery is a rare event that
      is usually related to prior disease or family history. Factors that contribute to
      the appearance of ACS during delivery in women with healthy coronary arteries
      include high doses of drugs to suppress contractions or increase uterine muscle
      tone and cardiovascular instability of any kind. Clinical and
      electrocardiographic abnormalities (eg, ST segment depression) that are
      suggestive of ACS have been reported to occur during cesarean section but without
      subsequent enzyme or echocardiographic abnormalities.

PMID- 18333388
TI  - [Is routine radiologic confirmation of central venous catheter positioning
      necessary?].

PMID- 18333389
TI  - [Delayed chylothorax after parenteral nutrition via the internal jugular vein].

PMID- 18333390
TI  - [Brachial fascial compartment hematoma after brachial plexus anesthesia with
      axillary nerve stimulation].

PMID- 18333391
TI  - [Severe methemoglobinemia due to aniline intoxication].

PMID- 18333392
TI  - [Severe bleeding from the radial artery after puncture for blood gas analysis in
      a patient with kidney failure receiving antiplatelet therapy].

PMID- 18333393
TI  - [Value of consent from patients aged under 18 years].

PMID- 18333394
TI  - [Major ambulatory surgery in a patient with alternating hemiplegia of childhood].

PMID- 18333395
TI  - [Incomplete axillary block and sedation with ketamine in a patient with myotonic
      dystrophy].

PMID- 18333396
TI  - [Systemic mastocytosis and anesthesia: a case report].

PMID- 18333397
TI  - [Spinal anesthesia after brachial plexus block with the posterior approach].

PMID- 18333398
TI  - [Massive edema of cervical interstitial tissue during shoulder arthroscopy].

PMID- 18333400
TI  - The systematical analysis of oriental pulse waveform: a practical approach.
AB  - With the view to set up the oriental pulse database as well as objective
      diagnosis standards, this study has designed and manufactured a digital pulse
      diagnosis system that uses a high-performance microprocessor on the basis of
      systematic pulse diagnosis methodology. The algorithm for extracting significant
      points has been proposed to precisely interpret the pulse signals that have
      various kinds of noises, and pulse measurement tests were conducted on many
      patients at a hospital. Much of the clinical data attained by the digital pulse
      diagnosis system has been compared with the clinical findings made by the doctors
      in charge of patients. As a result of this comparison and analysis, the study has
      found out that the two findings showed almost identical opinions. On this basis,
      an objective diagnostic parameter clinical diagnosis has been presented.

PMID- 18333399
TI  - Disparities in health information quality across the rural-urban continuum: where
      is coded data more reliable?
AB  - The growing application of evidence-based medicine practices across U.S.
      healthcare has created greater dependence on information resources, especially
      related to quality and consistency of data. The manipulation of data through
      coding and classification of patient information presents a critical process
      where the quality of information, as well as perceived quality of care, could
      potentially suffer. Where recent regulatory standards, such as HIPAA, create
      additional requirements for consistency in coding of health information, it
      becomes apparent that meaningful health outcomes assessment is, in part, an
      indicator of data quality as well as clinical quality. In a national survey of
      16,000+ accredited health information managers we found most respondents reported
      that significant coding errors existed in 5% or less of the records in their
      institutions. Within specific organizations, however, coding errors existed in
      six to ten percent of their records, and at times exceeded 20%. Regional
      variation in reported coding error and inconsistency ranged widely, occurring
      across organizations as well as population concentrations. Metropolitan-based
      organizations tended to have somewhat worse reported overall coding accuracy,
      compared to suburban and rural areas. At a national level there will need to be
      some degree of coding and classification uniformity across population areas, if
      healthcare professionals are expected to rely on comparative evidence benchmarks
      to fully assess medical outcomes data. Related impacts on comparative cost and
      clinical performance assessment are discussed.

PMID- 18333401
TI  - Classification of EEG recordings by using fast independent component analysis and
      artificial neural network.
AB  - Since there is no definite decisive factor evaluated by the experts, visual
      analysis of EEG signals in time domain may be inadequate. Routine clinical
      diagnosis requests to analysis of EEG signals. Therefore, a number of automation
      and computer techniques have been used for this aim. In this study we aim at
      designing a MLPNN classifier based on the Fast ICA that accurately identifies
      whether the associated subject is normal or epileptic. By analyzing a data set
      consisting of 100 normal and 100 epileptic EEG time series, we have found that
      the MLPNN classifier based on the Fast ICA achieved and sensitivity rate of 98%,
      and specificity rate of 90.5%. The results demonstrate that the testing
      performance of the neural network diagnostic system is found to be satisfactory
      and we think that this system can be used in clinical studies. Since the time
      series analysis of EEG signals is unsatisfactory and requires specialist
      clinicians to evaluate, this application brings objectivity to the evaluation of
      EEG signals.

PMID- 18333402
TI  - Automated identification of diabetic type 2 subjects with and without neuropathy
      using wavelet transform on pedobarograph.
AB  - Diabetes is a disorder of metabolism-the way our bodies use digested food for
      growth and energy. The most common form of diabetes is Type 2 diabetes. Abnormal
      plantar pressures are considered to play a major role in the pathologies of
      neuropathic ulcers in the diabetic foot. The purpose of this study was to examine
      the plantar pressure distribution in normal, diabetic Type 2 with and without
      neuropathy subjects. Foot scans were obtained using the F-scan (Tekscan USA)
      pressure measurement system. Various discrete wavelet coefficients were evaluated
      from the foot images. These extracted parameters were extracted using the
      discrete wavelet transform (DWT) and presented to the Gaussian mixture model
      (GMM) and a four-layer feed forward neural network for classification. We
      demonstrated a sensitivity of 100% and a specificity of more than 85% for the
      classifiers.

PMID- 18333403
TI  - A decision support system for telemedicine through the mobile telecommunications
      platform.
AB  - In this paper we have discussed the application of artificial intelligence in
      telemedicine using mobile device. The main goal of our research is to develop
      methods and systems to collect, analyze, distribute and use medical diagnostics
      information from multiple knowledge sources and areas of expertise. Physicians
      may collect and analyze information obtained from experts worldwide with the help
      of a medical decision support system. In this information retrieval system,
      modern communication tools such as computers and mobile phones can be used
      efficiently. In this work we propose a medical decision support system using the
      general packet radio service (GPRS). GPRS, a data extension of the mobile
      telephony standard Global system for mobile communications (GSM) is emerging as
      the first true packet-switched architecture to allow mobile subscribers to
      benefit from high-speed transmission rates and run JAVA based applications from
      their mobile terminals. An academic prototype of a medical decision support
      system using mobile device was implemented. The results reveal that the system
      could find acceptance from the medical community and it could be an effective
      means of providing quality health care in developing countries.

PMID- 18333404
TI  - A co-payment for consultant services: primary care physicians' referral
      actualization.
AB  - Prospective evaluation of the effect of a new copayment for specialists
      consultations on actualization of referrals (2,432 patient), was examined.
      Actualization of the appointment, reasons for not actualizing, and
      sociodemographic characteristics were recorded. Actualization was 85.1% in
      community consultation clinics and 91.7% in hospital outpatient clinics. The main
      reasons for non actualization were: inability to reach the clinic (53.4%), the
      problem had resolved (15%), and co-payment (2%). In addition, 19.1% stated that
      they did not actualize a past consultant visit due to co-payment. Referring
      physicians noted that co-payment had some effect on their decision, especially
      with the elderly or lower income patients. A relatively small compulsory co
      payment was not found to have a long term effect on utilization of specialists'
      services.

PMID- 18333405
TI  - The adaptive ARMA analysis of EMG signals.
AB  - In this study, Adaptive auto regressive-moving average (A-ARMA) analysis of EMG
      signals recorded on the ulnar nerve region of the right hand in resting position
      was performed. A-ARMA method, especially in the calculation of the spectrums of
      stationary signals, is used for frequency analysis of signals, which give
      frequency response as sharp peaks and valleys. In this study, as the result of A
      ARMA method analysis of EMG signals frequency-time domain, frequency spectrum
      curves (histogram curves) were obtained. As the images belonging to these
      histograms were evaluated, fibrillation potential widths of the muscle fibers of
      the ulnar nerve region of the people (material of the study) were examined.
      According to the degeneration degrees of the motor nerves, 22 people had
      myopathy, 43 had neuropathy, and 28 were normal.

PMID- 18333406
TI  - Cost-effectiveness of implantable cardioverter-defibrillators in Brugada syndrome
      treatment.
AB  - Brugada syndrome is characterized by an ST-segment elevation in the right
      precordial ECG leads and a high incidence of sudden death in patients with
      structurally normal hearts. Some trials have demonstrated that the cost
      effectiveness of ICD implantation treatment in patients with structurally
      abnormal hearts is more favorable than that of control treatment. We used Treeage
      pro 2005 to estimate costs and survival among the Brugada syndrome patients who
      received either an ICD or were treated by control therapy of Ito-blocking
      properties (quinidine) or beta-blockers (propranolol). In conclusion, our
      analysis suggests that prophylactic implantation of an ICD has good cost
      effectiveness in patients with Brugada syndrome who are at high risk of sudden
      death. ICD treatment has shown a cost-effectiveness ratio below $9591 per QALY
      gained from trials of defibrillator vs beta-blockers for Unexplained Death in
      Thailand (DEBUT). The control therapy of quinidine may be a good choice for
      patients who are infants or living in developing countries.

PMID- 18333407
TI  - 3D surface measurement for medical application--technical comparison of two
      established industrial surface scanning systems.
AB  - In 3D mapping of flexible surfaces (e.g. human faces) measurement errors due to
      movement or positioning occur. Aggravated by equipment- or researcher-caused
      mistakes considerable deviations can result. Therefore first the appliances'
      precision handling and reliability in clinical environment must be established.
      Aim of this study was to investigate accuracy and precision of two contact-free
      3D measurement systems (white light vs. laser). Standard specimens of known
      diameter for sphere deviation, touch deviation and plane deviation were tested.
      Both systems are appropriate for medical application acquiring solid data (<mm).
      The more complex white-light system shows better accuracy at 0.2 s measuring
      time. The laser system is superior concerning robustness, while accuracy is
      poorer and input time (1.5-2.5 s) longer. Due to the clinical demand the white
      light system is superior in a laboratory environment, while the laser system is
      easier to handle under non-laboratory conditions.

PMID- 18333408
TI  - A hybrid fuzzy-neural system for computer-aided diagnosis of ultrasound kidney
      images using prominent features.
AB  - The objective of this work is to develop and implement a computer-aided decision
      support system for an automated diagnosis and classification of ultrasound kidney
      images. The proposed method distinguishes three kidney categories namely normal,
      medical renal diseases and cortical cyst. For the each pre-processed ultrasound
      kidney image, 36 features are extracted. Two types of decision support systems,
      optimized multi-layer back propagation network and hybrid fuzzy-neural system
      have been developed with these features for classifying the kidney categories.
      The performance of the hybrid fuzzy-neural system is compared with the optimized
      multi-layer back propagation network in terms of classification efficiency,
      training and testing time. The results obtained show that fuzzy-neural system
      provides higher classification efficiency with minimum training and testing time.
      It has also been found that instead of using all 36 features, ranking the
      features enhance classification efficiency. The outputs of the decision support
      systems are validated with medical expert to measure the actual efficiency. The
      overall discriminating capability of the systems is accessed with performance
      evaluation measure, f-score. It has been observed that the performance of fuzzy
      neural system is superior compared to optimized multi-layer back propagation
      network. Such hybrid fuzzy-neural system with feature extraction algorithms and
      pre-processing scheme helps in developing computer-aided diagnosis system for
      ultrasound kidney images and can be used as a secondary observer in clinical
      decision making.

PMID- 18333409
TI  - Anatomo-radiological study of the superficial musculo-aponeurotic system of the
      face.
AB  - The aim of the study was to analyse the appearance of the superficial muscolo
      aponeurotic system (SMAS) in radiological images (Magnetic Resonance -MR- and
      Computed tomography -CT- scans, 10M, 10F randomly selected) in the three regions
      of the face (the parotid and cheek regions and the nasolabial fold). In axial CT
      images, the SMAS appears as a relatively hyperdense tortuous line between the
      hypodense superficial fibroadipose tissue (SAT) and the hypodense deep adipose
      tissue (DAT). In parotid region SAT is well represented (mean thickness 4.32 +/-
      2.9 mm), whereas DAT is very thin (0.33 +/- 0.48 mm); SMAS appears as a thin
      hyperdense line, close to the parotid gland (0.76 +/- 0.43 mm). In cheek region,
      SAT is well represented (5.57 +/- 1.17 mm), whereas DAT is thinner (2.94 +/- 0.62
      mm), and SMAS is well recognisable (1.69 +/- 0.52 mm). At the level of the
      nasolabial fold, the SAT is poorly represented (0.37 +/- 0.06 mm); the SMAS
      continues in the mimic muscles (2.41 +/- 0.05 mm), and DAT shows a mean thickness
      of 2.15 +/- 0.63 mm. In the MR examination, the SMAS appears as a thin continuous
      line hypointense in the T1-and T2-weighted sequence, from parotid region to
      nasolabial fold, comprising mimic muscles in the anterior region of the cheek and
      at the level of the nasolabial fold. No significative differences in thickness
      between CT and MR were found. Our anatomo-radiological study confirms that the
      subcutaneous architecture of the face consists of multiple layers of tissues that
      connect facial muscles with the dermis. This pattern of arrangement shows a
      progressive centrifugal thinning towards the adjacent regions.

PMID- 18333410
TI  - Is the lattice dystrophy of the cornea due to developmental anomalies of neural
      crest cells during embryogenesis (neurocristopathies)?
AB  - With the present paper authors try to give an embryological approach in
      understanding etiopathogenesis of lattice corneal dystrophy (LCD). The case of a
      41-years-old man affected by isolated LCD has been examined at the Ophtalmologic
      Clinic of the University of Catania, Italy. Sore cornea has been excised during
      cornea transplantation, and it has been examined by transmission electron
      microscopy (TEM). Results confirm classic submicroscopic findings described in
      literature. However these findings offer possibility to consider an embryological
      interpretation of LCD pathogenesis. Our findings with those of literature put
      forward hypothesis of a hereditary etiopathogenetical role exerted by
      keratocytes, direct derivatives of neural crest cells during embryogenesis,
      probably via an abnormal gene expression in producing proteinaceous precursor of
      amyloid substance (APP). LCD could be considered a neurocristopathy.

PMID- 18333411
TI  - Human temporomandibular joint morphogenesis.
AB  - Temporomandibular joint morphogenesis was studied. Ranging in age of fetuses
      examined was from 6 to14 weeks' gestation. Our results showed the condyle so
      first element that appear between 6 degrees and 8 degrees week (condylar
      blastema). After a week appear temporal elements. Disk appear at the same time of
      glenoid blastema and it reaches an advanced differentation before of the condyle
      and temporal element, so these don't effect machanical compression on mesenchyma
      where we find the disk. So we think that the disk result of genetic expression
      and it isn't the result of mechanical compression. The inferior joint cavity
      appear to 12 week. The superior joint cavity appear to 13-14 week. In conclusion,
      the appearance of the condyle is the first event during TMJ morphogenesis, with
      its initial bud, in form of a mesenchymal thickening, becoming detectable between
      the sixth and eight week of development, when all the large joints of the limbs
      are already well defined.

PMID- 18333412
TI  - Right medial internal jugular vein: a reversed carotid sheath.
AB  - Venous access is often essential in critical care medicine. The internal jugular
      vein (IJV) often provides reliable blood flow when subjected to cannulation.
      However, anatomical variations of the IJV have been reported as the cause of
      unsuccessful and complicated venous cannulation. We report ultrasonographic
      findings of an extremely rare variant of the right IJV in which this structure
      was located medial to the common carotid artery in the lower neck. A review of
      the literature on this topic is presented.

PMID- 18333413
TI  - Periodontal morphological microcirculation in oral lichen planus.
AB  - This study aimed at evaluating possible differences in the vascular pattern (of
      periodontal mucosa microcirculation) between healthy patients and patients
      suffering from PLP (periodontal lichen planus). Fifty-four patients (27 patients
      suffering from PLP and 27 healthy patients) were examined by means of
      videocapillaroscopy. The following area was examined for each patient:
      periodontal mucosa corresponding to 1.1 and 2.1. The following parameters were
      analyzed on every capillaroscopic image: capillary loop length, loop diameter,
      capillary tortuosity, capillary density, avascular areas, possible
      microhaemorrhages, distinctive morphology. The results obtained using
      videocapillaroscopic software were subjected to statistical analysis. The
      following parameters showed statistically significant differences: density, loop
      length, total diameter. This study and the research carried out over two years
      (from 2004 to 2006) have allowed us to confirm the increase in capillary diameter
      and density in PLP patients compared to the control patients. Besides, a
      remarkable increase in capillary density has been shown, which indicates a strong
      angiogenetic activity in PLP patients.

PMID- 18333414
TI  - [Genetic thrombophilic defects (Factor V Leiden, prothrombin G20210A, MTHFR
      C677T) in women with recurrent fetal loss].
AB  - Maternal thrombophilia (inherited and acquired) has recently been identified as a
      major cause of thrombembolism, but it may also contribute to adverse pregnancy
      outcomes and recurrent pregnancy loss. To determine the association of specific
      inherited thrombophilias and recurrent fetal loss (RFL), three gene mutations
      (Factor V Leiden, prothrombin G20210A, MTHFR C677T) were investigated. The
      prevalence of the thrombophilic markers was compared in 156 women with history of
      fetal loss in different trimester of pregnancy and 80 matched controls. At least
      one thrombophilic defect was found in 28.2% of total study group women compared
      with 16.2% in controls (p=0.06; OR-2.02) and in 50% of women with RFL in third
      trimester (p=0.008; OR-5.15). Factor V Leiden was more common in the group of
      women with fetal loss in third trimester (37.5%) compared to the controls (6.2%)
      (p=0.002; OR-9.0). Presence of FVL was associated with a significant increased
      risk for RFL in second and third trimester (OR-6.25; P<0.001) and significant
      protection for RFL in first trimester (OR-0.16; P<0.001). Mutation prothrombin
      G20210A or MTHFR C677T was more common in group of women with fetal loss in first
      trimester compared to the controls (28.3% vs. 11.2% respectively; p=0.009; OR
      3.11). The presence of either of these mutations was associated with no
      significant increased risk for RFL in first trimester (OR-2.5). Genetic
      thrombophilic defects are common in women with RFL and are associated with late
      fetal loss. This association is manifest by FVL rather than total number of
      defects involved.

PMID- 18333415
TI  - [Hemodynamic evaluation in early pregnancy. Part II. Embryonic circulation].

PMID- 18333416
TI  - [Is the breech presentation and delivery normal or pathological?].
AB  - The authors share their opinion, comparing their personal experience with the
      data in the world literature.

PMID- 18333417
TI  - [Role of growth factors in development of preeclampsia].

PMID- 18333418
TI  - [Vaccines for precancer and cancer of uterine cervix. I. Prophylactic HPV
      vaccines].
AB  - The causative relation of human papilloma virus with the cervical cancer and its
      precursors is well known. Effective vaccines, based on virus like particles (L1
      and L2) against these viruses have been developed. They ensure primary
      prophylaxis through the production of neutralized antibodies. In this connection,
      the present review summarized the existing world experience of the clinical
      application of the developed bi- and quadrivalent HPV vaccines, according to
      beginning of their occurrence.

PMID- 18333419
TI  - [Diagnostic problems in a case of fibroma ovarii].
AB  - Fibroma ovarii is a solid benign tumor which consists of fibrous tissue. It is
      usually hard, but there may be small cystic spaces due to degenerative changes.
      The incidence of fibroma ovarii is about 8 to 10%. The authors present a case of
      this tumor with difficulties in diagnosis before operation.

PMID- 18333420
TI  - [Registry of patients with advanced ovary carcinoma in the province of Stara
      Zagora].
AB  - A representative inquiry has been conducted including the most important
      parameters from the medical files of 61 out-patients with ovarian carcinoma in
      III or IV stage in the province of Stara Zagora for the period 1997, 1998 and
      1999. The prevailing majority are urban citizens /72.13%/, mainly aged over 60
      /62.29%/. The highest is the number of patients who gave birth to 1 child
      /42.62%/, followed by those with 2 children /37.70%/. In 16.39% of women
      occupational harms were established. In 9.83% of the patients benign tumours were
      found, in 6.55% malignant as concomitant diseases. In most cases the treatment is
      surgery in combination with chemotherapy. Histological screening of ovarian
      tumours showed predominance of the serous carcinoma in the papilliferum-
      /40.98%/. A combined chemotherapy. including mostly cys-platinum, is used in the
      treatment of patients with tumour in the ovary in the Clinic of Oncological
      Diseases of Stara Zagora.

PMID- 18333421
TI  - Economics of mental health. New challenges and new perspectives.

PMID- 18333422
TI  - Mental health system financing in developing countries: policy questions and
      research responses.
AB  - To what extent does previous and existing health economics research directly
      address key health system financing issues facing mental health services in
      developing countries? By mapping WHO's health systems framework onto mental
      health, three key financing questions for mental health are identified: the
      sufficiency of resources for mental health; the protection of individuals or
      households against the economic consequences of mental ill-health; and the
      efficient use of available resources for mental health. Research efforts to date
      have mainly focused on the evaluation of intervention costs in relation to mental
      health outcomes (the efficiency question). There is a need to achieve a greater
      balance between economic analysis (aimed at identifying best buys) versus
      financial planning (scaling up the delivery or implementation of interventions
      shown to be cost-effective). In addition, a better understanding and clearer
      articulation of the negative impact of mental disorders at the household level is
      needed, together with ways of alleviating financial burden via appropriate and
      affordable pre-payment financing mechanisms.

PMID- 18333423
TI  - "The trouble with QALYs...".
AB  - This paper summarises the use of QALYs in evaluating changes in mental health
      states, highlighting the benefits and challenges of their use in this field. The
      general principles underlying the QALY measure and the most common methods of
      measuring QALYs are discussed briefly. Evidence of the usefulness and problems of
      using this generic measure of health-related quality of life are provided from a
      sample of recent studies relating to depression, schizophrenia, attention deficit
      hyperactivity disorder and dementia. In each case, attempts were made to use
      QALYs to measure changes in health states. While in principle, the QALY is
      enormously attractive, its suitability for measuring changes in many mental
      health conditions remains open to doubt as existing tools for generating QALY
      scores such as the EQ-5D have tended not to perform sufficiently well in
      reflecting changes in many mental health states. New developmental work is needed
      to construct better QALY-measuring tools for use in the mental health field. Both
      the conceptualisation and measurement of QALYs need to be built on a valid,
      comprehensive model of quality of life specific to a mental health disorder, to
      ensure that the resultant tool is sensitive enough to pick up changes that would
      be expected and seen as relevant in the course of the illness.

PMID- 18333424
TI  - The economics of mental health in the workplace: what do we know and where do we
      go?
AB  - To provide an overview of the economic impact of poor mental health in the
      workplace and assess the extent to which economic evaluation has been used to
      further the case for investment in workplace based mental health programmes.
      Rapid scoping review of published and grey literature. The socio-economic costs
      of poor mental health in the workplace are substantial but conservative, as few
      studies have included productivity losses from work cutback, as well as
      absenteeism. While few economic evaluations of workplace based mental health
      interventions were identified, the available evidence base suggests that they
      have the potential to be highly cost effective. Much of this evidence may be from
      the US and be less applicable elsewhere; it may also have been solely published
      in company documents making assessment of methodological quality difficult. The
      potential economic case for workplace based mental health interventions appears
      good. More collaboration between policy makers and the private sector would help
      facilitate rigorous and transparent economic evaluations. A number of evaluations
      are planned. The challenge is to build on these initiatives, in order to address
      what remains a major gap in our knowledge on the economics of mental health.

PMID- 18333425
TI  - An introduction to sample size calculations in clinical trials.

PMID- 18333426
TI  - Managing complex problems: treatment for common mental disorders in the UK.
AB  - AIMS: This paper aims to describe current trends in the UK primary care
      management of common mental disorders and explore the appropriateness of
      differing management approaches in light of the course and common complications
      of these disorders. METHODS: It highlights key findings concerning the course and
      comorbidity of depression to indicate that depression and associated mental
      illnesses may often form part of more complex patterns of ill health and that
      these conditions have a clear potential for chronicity. A narrative review of
      studies providing detail of depression prevalence in selected comorbid conditions
      is presented for this purpose. CONCLUSION: The presentation and course of common
      mental disorders indicate organizational changes in health service delivery, and-
      for a sizeable patient group--the use of chronic disease management strategies.

PMID- 18333427
TI  - Short-term depressive symptoms and 30-day prognosis of hospitalized patients with
      acute coronary syndromes; the Greek study of acute coronary syndromes (GREECS).
AB  - AIMS: We evaluated whether short-term depressive symptoms are associated with the
      30-day prognosis of hospitalized patients presented with acute coronary syndromes
      (ACS). METHODS: A sample of 6 hospitals located in Greek urban and rural regions
      was selected. From October 2003 to September 2004, we recorded the non-fatal
      admissions of ACS. Assessment of depressive symptoms, during past month, was
      based on the CES-D scale (Radloff S., 1977). RESULTS: 2172 patients were included
      in the study (1649, 76% were males). The mean CES-D score was 13.5+/-12 in male
      patients and 13.6+/-12 in females (p=0.89). Compared to patients with angina
      those who had non-Q-wave MI or Q-wave MI had higher CES-D score (12.3+/-11.6 vs.
      15.3+/-12.8 vs. 13.2+/-11.9, p=0.001). The number of events during the first 30
      day following discharge was 9.2% in males and 9.7% in females. Multivariable
      logistic regression analysis revealed that 1-unit increase in CES-D was
      associated with 10% higher odds (95% CI 1.09-1.12) of re-current events (death or
      re-hospitalization), after adjusting for various socio-demographic, lifestyle and
      clinical factors. CONCLUSION: We revealed that short-term depressive symptoms are
      related to more severe disease and a worsen 30-day prognosis of patients
      hospitalized for ACS.

PMID- 18333428
TI  - [Sleep self-report measures: a literature review].
AB  - AIM: The widespread diffusion of sleep disorders (in particular, insomnia) in the
      general population and the presence of sleep complaints in many mental disorders
      and physical illnesses justifies an interest in their assessment and treatment,
      still today commonly underestimated. This study aims to describe the inexpensive
      and relatively easy-to-use self-report measures of sleep available in literature.
      METHOD: A literature search was conducted throughout the electronic literature
      database "Pubmed", selecting the pertinent articles published up to December
      2006. RESULTS: The recovered material takes the following fields into account:
      aspect of sleep measured, statistical population, structure, time frame, sub
      scales and psychometric properties. International literature presents somewhat
      heterogeneous sleep self-evaluation tools, which mainly measure sleep quality and
      the specific causes of sleep interference. As for the Italian context, the
      recovered material is somewhat modest, taking into account the number of
      publications. CONCLUSIONS: The critical points met in this review have led us to
      underline the characteristics of a hypothetical tool for sleep assessment to
      include in routine diagnoses.

PMID- 18333430
TI  - [The assessment of patient involvement across consultation. The Italian version
      of the OPTION scale].
AB  - AIM: To present the Italian version of the OPTION (observing patient involvement)
      rating scale, developed in UK by Elwyn et al. (2005), and its psychometric
      characteristics, together with some findings when applied on the consultations
      transcripts of a group of Italian General Practitioners. METHODS: The OPTION
      scale assesses the extent to which clinicians involve patients in decisions and
      consists of 12 items to be rated on a 5 point scale (from 0--behaviour not
      observed to 4--high standard). The scale was applied to 235 transcripts of
      audiotaped consultations conducted by 6 male GPs. Interrater and test-retest
      reliability and internal validity indices were calculated on a subsample of 30
      transcripts. RESULTS: The Italian language version of OPTION showed good
      psychometric properties, similar to those reported for the original version. The
      ratings obtained for 235 consultations showed for each OPTION item a skewed
      distribution: the majority of scores (> 70%) were between 0 (behaviour absent)
      and 2 (minimum skill level). CONCLUSIONS: The Italian language version of OPTION
      seems a reliable instrument to assess patient involvement in primary care
      settings also in Italy. The clustering of low scores confirms previous findings
      that clinicians without a specific training obtain very low levels of patient
      involvement in the decision making process.

PMID- 18333429
TI  - Which community care for patients with schizophrenic disorders? Packages of care
      provided by Departments of Mental Health in Lombardy (Italy).
AB  - AIMS: The treatment of schizophrenic disorders is the most important challenge
      for community care. The analysis focuses on packages of care provided to 23.602
      patients with a ICD-10 diagnosis of schizophrenic disorder and treated in 2001 by
      the Departments of Mental Health in Lombardy, Italy. METHODS: Packages of care
      refer to a mix of treatments provided to each patient during the year by
      different settings. Direct costs of the packages were calculated. Linear
      Discriminant Analysis has been used to link socio-demographic and diagnostic sub
      groups of the patients to packages of care. RESULTS: People with schizophrenic
      disorders received relatively few care packages: only four packages involved more
      than 5%. Two thirds of the patients received only care provided by Community
      Mental Health Centres. In the other two packages with a percentage over 5%, the
      activity was provided by CMHCs, jointly with General Hospitals or Day Care
      Facilities. Complex care packages were rare (only 6%). As well as the intensity,
      also the variety of care provided by CMHCs increased with the complexity of care
      packages. In Lombardy more than half of the resources were spent for
      schizophrenia. The range of the costs per package was very wide. LDA failed to
      link characteristics of the patients to packages of care. CONCLUSIONS: Care
      packages are useful tools to understand better how mental health system works,
      how resources have been spent and to point out problems in the quality of care.

PMID- 18333431
TI  - [Antidepressant drug prescribing in the general population and among problematic
      drug users in the province of Bologna (Italy)].

PMID- 18333432
TI  - Anxiety and socio-economic status among healthy adults: the ATTICA study.

PMID- 18333433
TI  - [Involuntary admission to the psychiatric unit of Cosenza's Hospital: a
      retrospective study over the twenty-five year period, 1978-2003].

PMID- 18333434
TI  - [Estimation of carbon release from shrubs, herbages and litters in Daxing' an
      Mountains by forest fires in 1980-1999,].
AB  - By using emission factor (EF), this paper estimated the carbon release and the
      emission of carbon-containing gases from the shrubs, herbages and litters in main
      forest types in Daxing' an Mountains by forest fires in 1980-1999. The results
      showed that the EF of shrubs, herbages and litters differed in different forest
      types, with the maximum and minimum EF of CO2 being 93.08% and 82.56%,
      respectively in Ledum palustre - Larix gmelinii forest and Pinus sylvestris var.
      mongolica forest, the maximum EF of CO and C(X)H(Y) being 10.25% and 0.84%,
      respectively in P. sylvestris var. mongolica forest, and the minimum EF of CO and
      C(X)H(Y) being 6.55% and 0.30%, respectively in L. palustre - L. gmelinii forest.
      Combined with the data of biomass and carbon storage of shrubs, herbages and
      litters in different forests, it was estimated that the total carbon release from
      shrubs, herbages and litters by forest fires from 1980 to 1999 accounted for 6.56
      Tg and 0.33 Tg x a(-1), occupying 11.55%-16.30% of the total annual emissions in
      China by forest fires, and the emission of CO2, CO and C(x)H(y) was 22.03 Tg,
      accounting for 85.20%, 14.21% and 0.59% of the total carbon-containing gases
      emission, respectively.

PMID- 18333435
TI  - [Distribution characteristics of delta13C values in different organs of Abies
      georgei growing at alpine timberline].
AB  - Based on the analysis of the distribution characteristics of delta13C values in
      the needle, twig, branch, trunk, and root of different age Abies georgei growing
      at the timberline of Sergyemla Mountain on the southeast edge of Tibetan Plateau,
      this paper studied the process or extent of post-photosynthetic delta13C
      fractionation and its affecting factors. The results showed that the organ
      specific difference in delta13C values was highly significant (P < 0.001), with
      the sequence of trunk (-24.19 per thousand +/- 0.34 per thousand) > branch (
      24.56 per thousand +/- 0.62 per thousand) > root (-25.05 per thousand +/- 1.08
      per thousand) > twig (-25.12 per thousand +/- 0.54 per thousand) > needle (-7.25
      per thousand +/- 0.63 per thousand), which suggested that an obvious post
      photosynthetic delta13C fractionation was existed between photosynthetic and non
      photosynthetic organs. With increasing age of needle and twig, the delta13C value
      in needle decreased significantly, while that in twig showed a reverse pattern (P
      < 0.01). The delta13C value in needle increased significantly (P < 0.01) from
      lower canopy to higher canopy, whereas no significant difference (P > 0.05) of
      delta13C value in twig was observed among different canopy heights. A significant
      vertical gradient of delta13C value existed in the branches at a distance of 2.5
      m from trunk (P < 0.01), but disappeared at a distance of 1.5 m or 0.5 m. At the
      same canopy height, the delta13C value in twig decreased with increasing distance
      from trunk, which was most obvious in the twigs of middle and lower canopies. All
      of these suggested that post-photosynthetic delta13C fractionation occurred in
      alpine A. georgei, and the carbon need for the growth of height-specific tree
      stems or branches was not wholly supplied by the corresponding segment of the
      tree crown at the same height.

PMID- 18333436
TI  - [Genetic diversity of endangered plant Torreya jackii: a study with RAPD
      markers].
AB  - With random amplified polymorphic DNA (RAPD) techniques, this paper studied the
      genetic diversity and genetic differentiation of Torreya jackii, an endangered
      plant endemic to China. In the 180 individuals of 9 T. jackii natural
      populations, 180 repetitive loci were detected by using 12 random primers, among
      which, 119 were polymorphic. At species level, the percentage of polymorphic loci
      (P) was 66.11%, and the genetic diversity estimated by Shannon information index
      (I) and Nei's index (h) was 0.3087 and 0.2015, respectively, suggesting that the
      genetic diversity at species level was relatively high. However, at population
      level, the genetic diversity was relatively low (P = 23.76% , I = 0.1221, and h =
      0.0813). The analysis of molecular variance (AMOVA) showed that 42.57% of genetic
      variance was found within populations, and 57.43% of it was resided among
      populations. The coefficient of gene differentiation (G(st)) was 0.5965,
      indicating the high genetic differentiation among the populations of T. jackii,
      and the gene flow among the populations was quite low, being 0.3382. The
      bottleneck effect, population isolation, and low gene flow among populations
      would have contributed to such a population genetic structure in T. jackii. The
      averaged genetic distance among 9 T. jackii populations was 0.1630. By using the
      unweighted pair group method with arithmetic mean (UPGMA), the 9 populations
      could be divided into two groups, i. e., Zhejiang group and Fujian group. It was
      proposed that in the ex situ conservation of T. jackii, the gcrmplasm
      transferring among populations should be avoided.

PMID- 18333437
TI  - [Soil respiration in temperate secondary forest and Larix gmelinii plantation in
      Northeast China].
AB  - With Li-6400-09 chamber, the soil respiration rate in adjacent stands of
      temperate secondary forest and Larix gmelinii plantation in Maoershan Mountain of
      Heilongjiang Province was measured from May to October, 2006. The results showed
      that similar to the variation of soil temperature, the daily pattern of soil
      respiration could be expressed as a one-humped curve. Over the study period, soil
      respiration rate varied from 0.43 to 7.26 micromol CO2 x m(-2) x s(-1) in
      secondary forest, and from 0.63 to 4.70 micromol CO2 x m(-2) x s(-1) in L.
      gmelinii plantation. The maximum soil respiration rate occurred from July to
      August, and the minimum in October. From May to August, soil respiration rate was
      obviously higher in secondary forest than in L. gmelinii plantation. The
      respiration rate of litter layer during the study period varied from -0.65 to
      1.26 micromol CO2 x m(-2) x s(-1) in secondary forest, and from -0.43 to 0.47
      micromol CO2 x m(-2 ) x s(-1) in L. gmelinii plantation. Soil respiration had a
      strong exponential correlation with soil temperature, especially the temperature
      at 5 cm depth. The Q10 value at 5 cm depth was 3.61 and 3.07, respectively in
      secondary forest and L. gmelinii plantation. There was a significant correlation
      between soil respiration and the soil water content at 10-20 cm depth in
      secondary forest, but less correlation was observed between them in L. gmelinii
      plantation.

PMID- 18333438
TI  - [Soil macropore characteristics under typical vegetations in Liupan Mountains].
AB  - The radius and density of soil macropores under eight typical vegetations in
      Liupan Mountains of Northwest China were studied by using water breakthrough
      curves and Poiseuille equation. The results indicated that the radii of soil
      macropores ranged from 0.4 mm to 2.3 mm, and the weighted mean radii ranged from
      0.57 mm to 1.21 mm, with a mean of 0.89 mm. The density of soil macropores ranged
      from 57 individuals per dm2 to 1 117 individuals per dm2, with a mean of 408
      individuals per dm2. The macropores with radii bigger than 1.4 mm had a lower
      density, accounting for only 6.86% of the total. The area proportion of soil
      macropores ranged from 0.76% to 31.26%, with a mean of 10.82%. In study area, the
      density of soil macropores was higher in broadleaf forest than in coniferous
      forest, but basically the same in sub-alpine meadow and in broadleaf forest, as
      well as in shrubs and in coniferous forest. As for the area proportion of soil
      macropores, it was also higher in broadleaf forest than in coniferous forest, but
      basically the same in shrubs and in broadleaf forest soil, as well as in sub
      alpine meadow and in coniferous forest.

PMID- 18333439
TI  - [Soil denitrification rates in different type riparian zones in maoershan
      mountainous region of China].
AB  - Soil samples were collected from forested, clear-cut, and grassy riparian zones
      under forest background and from forested and barren riparian zones under
      cropland background in the Maoershan mountainous region of China. The samples
      were incubated in laboratory, and their denitrification potentials were
      determined by nitrate-deduction method. The results showed that under crop-land
      background, soil denitrification rate was the highest in forested riparian zone
      and the lowest in barren riparian zone, with the deduction rate of nitrate varied
      from 46.79%-91.13% and 15.64% -81.84%, respectively. Under forest background,
      soil denitrification rate decreased in the order of clearcut > forested > grassy
      riparian zone, with the deduction rate of nitrate being 42.06%-90.39%, 28.24%
      85.73% and 21.44%-83.11%, respectively. The denitrification rate was higher in
      subsurface layer than in deeper layer, and the denitrification potential was
      limited by the available carbon and nitrate, being the greatest in the forested
      riparian zone under cropland background.

PMID- 18333440
TI  - [Spatiotemporal variation of carbon storage in forest vegetation in Sichuan
      Province].
AB  - Based on the modeling of forest biomass and timber volume and the 1974-2004
      forest inventory data, the spatiotemporal variation of carbon density and storage
      in forest vegetation in Sichuan Province was studied. The results showed that the
      forest carbon storage was increased from 300.02 Tg in 1974 to 469.96 Tg in 2004,
      with an annual increment of 1.51%, which suggested that the forests in Sichuan
      Province were the sink of CO2. However, owing to the increase of plantations, the
      average carbon density of forest vegetation decreased from 49.91 Mg x hm(-2) to
      37.39 Mg x Shm(-2), implying that Sichuan forests had a great potential of carbon
      sequestration through artificial forest management. The carbon storage in Sichuan
      forests had a spatial heterogeneity, and the ranked order was northwest alpine
      gorge area > southwest mountainous area > low-mountain area > hilly area >
      western plain. Forest carbon density increased from southwest area to northwest
      area, with the order of hilly area < northern plain < southwest mountain area <
      low-mountain area < northwest alpine gorge area. It was suggested that forest
      management according to different sub-regions would improve the potential of
      carbon sequestration in Sichuan forests.

PMID- 18333441
TI  - [Effects of ectomycorrhizal fungi on alleviating the decline of Pinus sylvestris
      var. mongolica plantations on Keerqin sandy land].
AB  - Based on the observations of air temperature, soil temperature, and root systems
      of Pinus sylvestris var. mongolica plantations on southeastern Keerqin sandy
      land, the decline mechanisms of the plantations were analyzed from the aspect of
      the effects of temperature on the growth and survival of ectomycorrhizal fungi
      (ECM). The results indicated that ECM could hardly survive with in 0-5 cm soil
      layer because of its high temperature environment, but the temperature condition
      in 20-40 cm soil layer was suitable for the survival and growth of ECM. 78% of
      the roots of 13-42 years old P. sylvestris var. mongolica tress were distributed
      in 20-40 cm soil layer, which suggested that the existence of ECM in this soil
      layer inhibited or alleviated the decline of the P. sylvestris var. mongolica
      plantations, and was not the inducing factor of the plantations' top withering,
      low growth rate, and tree death. The lack of ECM in surface soil layer (0-5 cm)
      could be one of the main reasons leading to the death of seedlings root systems,
      and thus, the failure of P. sylvestris var. mongolica plantations' regeneration.

PMID- 18333442
TI  - [Biomass allocation of Leymus chinensis population: a dynamic simulation study].
AB  - Based on a greenhouse simulation experiment, this paper studied the dynamics of
      the above- and below-ground biomass of Leymus chinensis populations with four
      planting densities (120, 240, 360 and 480 plants x m(-2)). The results showed
      that the above- and below-ground biomass of L. chinensis populations had an
      increasing trend with the growth, and increased with increasing planting density.
      However, the relative growth rates (RGRs) of the above- and below-ground biomass
      did not show significant difference among the L. chinensis populations. The ratio
      of root to shoot (RRS) of the L. chinensis populations increased with their
      growth, but did not show significant difference among the planting densities,
      implying that environmental factors were the controlling factors for RRS. There
      existed significant power function relationships between the above- and below
      ground biomass of L. chinensis individuals and populations, but the power
      function indices and coefficients varied with the planting density. It was
      suggested that the difference of microenvironment resulted from resources
      competition could induce the changes of L. chinensis RRS, and the latter could be
      used as a reference to quantitatively study the allocation of photosynthetic
      products.

PMID- 18333443
TI  - [A prediction model for forest fire-burnt area based on meteorological factors].
AB  - Based on statistic analysis theory, the occurrence patterns of forest fire in
      Heilongjiang Province were studied, and the prediction model for forest fire
      burnt area was established based on meteorological factors. The results showed
      that most of forest fires in Larix gmelinii forest region occurred from April to
      June and in October, and those in broadleaved Korean pine forest region mainly
      occurred from March to June and in October. By adopting the values of average
      wind speed, relative humidity and mean temperature, it was predicted that in L.
      gmelinii forest region, the first three months with greater probability of larger
      fire occurrence were March, May and June in order, while in broadleaved Korean
      pine forest region, they were May, March and April. The average precision of the
      model was 63.3%, suggesting that it could be used to predict the burnt area by
      forest fires.

PMID- 18333444
TI  - [Effects of moisture content in organic substrate on the physiological
      characters, fruit quality and yield of tomato plant].
AB  - With tomato cultivar Qifen as test crop, this paper studied its growth,
      physiological characters, fruit yield, fruit quality, and water use efficiency
      (WUE) under effects of relative moisture content of organic substrate. The
      results showed that with increasing moisture content in organic substrate, the
      plant height, stem diameter, node length, leaf area per plant, leaf pigment
      content, water potential, osmotic potential, root vigor, and fruit yield
      increased markedly, but fruit quality and WUE decreased significantly.
      Considering from the aspects of fruit yield, fruit quality and WUE, 80% moisture
      content of organic substrate could be used as a favorable quantitative index for
      the water management of tomato cultivation, under which, 26 kg x m(-2) fruit
      yield could be achieved. If only considering fruit quality, 50% moisture content
      could be used as the index for water management.

PMID- 18333445
TI  - [Effects of air temperature, solar radiation and soil water on dry matter
      accumulation and allocation of greenhouse muskmelon seedlings and related
      simulation models].
AB  - With different sowing dates and irrigation upper limits, the effects of air
      temperature, solar radiation and soil water on the dry matter accumulation and
      allocation of greenhouse muskmelon seedlings were studied, with related
      simulation models established. The results showed that the dry matter
      accumulation and allocation of the seedlings had correlations with the changes of
      effective accumulative temperature, accumulative solar radiation, and irrigation
      upper limits at different seasons in a year, but the correlation coefficients
      differed with sowing dates and irrigation upper limits. Comprehensive analysis
      showed that the dry matter accumulation model was an exponential function, while
      the dry matter allocation model was a conic function, both of which were driven
      by effective accumulative temperature. The constant term in the functions was
      driven by accumulative daily temperature difference and accumulative solar
      radiation, and the correlation was a linear function. Model test showed that the
      models were able to objectively simulate and predict the changes of plant dry
      matter accumulation and allocation, and possessed practical value for the growth
      analysis and production management of muskmelon seedling.

PMID- 18333446
TI  - [Effects of foliar spraying DA-6 on the photosynthetic rate and plant growth of
      strawberry in autumn].
AB  - With strawberry ' French 3' (Fragaria x ananassa Duch cv. French 3) as test
      material, this paper studied the effects of foliar spraying DA-6 at the rates of
      10, 20 and 30 mg x L(-1) in late autumn on its seedlings net photosynthetic rate,
      metabolism of reactive oxygen species, and plant growth. Compared with the
      control, foliar spraying DA-6 of 20 and 30 mg x L(-1) increased the net
      photosynthetic rate, chlorophyll a and b contents, and SOD and CAT activities
      significantly, and decreased the reactive oxygen and MDA contents. Moreover,
      foliar spraying DA-6 of 20 and 30 mg x L(-1) increased the average dry weight per
      leaf, and the dry mass of shoot and root significantly. The ratio of root to
      shoot after spraying DA-6 of 20 and 30 mg x L(-1) was 29.9% and 29.3% higher than
      the control, respectively. Foliar spraying appropriate concentration of DA-6 in
      late autumn could improve the plant growth of strawberry seedlings.

PMID- 18333447
TI  - [Effects of Cu2+ stress on leaf physiological indice and ultrastructure of
      Potamogeton malaianus].
AB  - With solution culture, this paper studied the toxic effects of different
      concentrations of Cu2+ (0, 2, 4, 6, and 8 mg x L(-1)) on the chlorophyll content,
      soluble protein content, protective enzyme activities, active oxygen generation,
      and ultrastructural changes in Potamogeton malaianus leaf. The results showed
      that with increasing concentration of Cu2+, the chlorophyll, carotenoid and
      soluble protein contents and superoxide dismutase (SOD) and peroxidase (POD)
      activities decreased, catalase (CAT) activity increased first and decreased then,
      while O2-*, H2O2, MDA and soluble sugar content increased. SDS-PAGE revealed that
      Cu2+ induced the disappearance or the decrease of the expression amount of four
      polypeptides with apparent molecular weights of 60.9, 18.8, 15.7, 22.3 and 30.0
      kDa. Transmission electron microscopy observation indicated that the higher Cu2+,
      concentration, the more serious damages the leaf organelles, especially
      chloroplast, mitochondria and nucleus, suffered. It was concluded that the death
      of P. malaianus plant under Cu2+ stress was resulted from the destruction of
      physiological function and structural foundation, and the disorder of
      physiological metabolism. The lethal concentration of Cu2+ could be 2-4 mg x L(
      1).

PMID- 18333448
TI  - [Responses of microbial biomass P to the changes of organic C and P in paddy
      soils under different fertilization systems].
AB  - Based on a fifteen years field experiment in double rice-cropping region of
      subtropical China, the responses of microbial biomass P (MB-P) to organic C and P
      in red paddy soils under different fertilization systems were investigated. The
      results indicated that a long-term input of organic carbon sources and the
      increasing soil organic carbon made soil microbial biomass remain at a high level
      (MB-C > 800 mg x kg(-1)), being a main reason of the increase of MB-P. Under long
      term zero chemical P fertilization, there was a significant decrease in soil
      total P (P < 0.05), but soil organic P increased by 29.3% on average. The
      inorganic P forms in deficit were mainly Al-P, Fe-P, Ca-P and O-P, with the
      lowest content of Al-P (only 0.5 mg x kg(-1) on average). The content of soil MB
      P under zero chemical P fertilization was much higher than that of Olsen-P.
      Correlation analysis showed that there was a significant relationship (P < 0.05)
      between MB-P and Al-P, from which, it was deduced that the utilization of Al-P,
      Fe-P, Ca-P and O-P by soil microbes could be the key approach of promoting these
      P forms transformed into available P. Chemical P fertilization combined with
      organic nutrient recycling could not only enlarge the soil P pool, but also
      improve the P availability.

PMID- 18333449
TI  - [Relationships between soil nutrients and rhizospheric soil microbial communities
      and enzyme activities in a maize-capsicum intercropping system].
AB  - By using plastic sheet and nylon mesh to partition the root systems of maize and
      capsicum in a maize-capsicum intercropping system, this paper studied the
      relationships between soil biological factors and nutritive status in the
      intercropping system, with no partitioning and maize monoculture and capsicum
      monoculture as the control. The results showed that intercropping maize and
      capsicum had its high superiority. In the treatments of no partitioning and nylon
      mesh portioning in the intercropping system, soil enzyme activities, microbial
      individuals and nutrient contents were significantly higher, compared with those
      in the treatments of nylon mesh partitioning and monocultures. All kinds of soil
      available nutrients showed significant or very significant positive correlations
      with soil biological factors, except that soil available Mg was negatively
      correlated with soil fungi and catalase activity. Pathway analysis indicated that
      in the intercropping system, soil urease, catalase, protease, and bacteria were
      the main factors affecting the accumulation of soil organic matter, saccharase
      was the most important factor affecting soil alkali-hydrolyzable N, urease was
      the most important factor affecting soil available P, and bacteria largely
      determined soil available K. Soil alkaline phosphatase and fungi selectively
      affected the accumulation of soil organic matter and available N, P and K. There
      was a slight negative correlation between soil actinomycetes and soil nutrients,
      suggesting that actinomycetes had little effect on soil nutrient formation.

PMID- 18333450
TI  - [Effects of successive cropping Rehmannia glutinosa on rhizosphere soil microbial
      flora and enzyme activities].
AB  - With the soils cropped Rehmannia glutinosa for one and two years as test
      materials, this paper studied the variations of microbial flora and enzyme
      activities in rhizosphere. The results showed that with increasing year of
      cropping, the numbers of bacteria and fungi in rihzosphere had a slight decrease.
      In the soil successively cropped R. glutinosa for two years, the number of
      actinomycetes in rihzosphere was 4 times higher, the ammonifier, aerobic
      azotobacter, sulphate reducer, denitrifier, and anaerobic cellulose-decomposer
      increased by 25.99, 45.39, 11.43, 1.36, and 1.43 folds, respectively, while
      aerobic cellulose-decomposer reduced by 86.74%, compared with those in the soil
      cropped R. glutinosa for one year. The root exudates of successively cropped R.
      glutinosa increased the activities of urease, polyhphenol oxidase, sucrase,
      protease and cellulase in rhizosphere by 62.87%, 9.43%, 47.91%, 139.62% and
      31.33%, respectively, but inhibited the activity of catalase. The findings
      suggested that successive cropping R. glutinosa would destroy the balance of
      rhizosphere soil microbial flora.

PMID- 18333451
TI  - [Effects of land use type on soil organic carbon storage in aquic brown soil].
AB  - The profile distribution of soil organic carbon (SOC), its storage, and
      carbon/nitrogen (C/N) ratio at the depth of 0-100 cm under different land use
      types were investigated in this paper. The results showed that the profile
      distribution of SOC varied significantly with land use type. The SOC contents in
      each soil layer in forestland, mowing land and wasteland were all higher than
      that in agricultural land. In all land use types, SOC was significantly
      correlated with soil total N. Soil C/N ratio generally decreased with depth,
      which was higher in forestland than in mowing land, wasteland and bare land, and
      was the lowest in agricultural land. At the depth of 0-100 cm, the annual
      sequestration of SOC in wasteland was 4.52, 4.25, 4.46 and 3.58 t x hm(-2) more
      than that in farmland with no fertilization, farmland with recycled manure
      application, farmland with N, P and K fertilization, and farmland with the
      application of both recycled manure and N, P and K, respectively, suggesting that
      wasteland had a great potential in increasing SOC storage.

PMID- 18333452
TI  - [CO2 flux and its correlation with soil temperature in winter wheat growth season
      under different tillage measures].
AB  - Based on a long-term experiment, this paper investigated the CO2 flux in winter
      wheat growth season under different tillage measures, and simulated the
      correlation between the flux and soil temperature by regression method. The
      results indicated that under different tillage measures, the average CO2 emission
      rate in winter wheat growth season was in the order of moldboard plow tillage (F)
      > minimum tillage (X) > no-tillage (M), with the value being 343.69, 337.54 and
      190.47 mg x m(-2) x h(-1), respectively. There was a significant exponential
      correlation between CO2 flux and soil temperature, which was most significant for
      the soil temperature at the depth of 10 cm under F, and relatively significant
      for the soil temperature at the depth of 10 and 20 cm under X and M. Simulating
      with the soil temperature at the depth of 10 cm, the CO2 flux in winter wheat
      growth season was estimated as 1.88 kg x m(-2) under F, 1.89 kg x m(-2) under X,
      and 1.03 kg x m(-2) under M.

PMID- 18333453
TI  - [Ammonia volatilization from rice field under different water conditions in lower
      Liaohe River Plain].
AB  - With ventilating chamber, this paper measured the ammonia volatilization from a
      meadow brown soil rice field after N fertilization under different water
      conditions in lower Liaohe River Plain. The results showed that there was an
      obvious ammonia volatilization after N fertilization. The total ammonia
      volatilization during rice growth period was 11.64-34.01 kg N x hm(-2),
      accounting for 4.66%-11.66% of applied N. The volatilization loss of applied N at
      different growth stages followed the order of tillering stage > booting stage >
      before transplanting, and the peak was appeared at 2-4 days after N
      fertilization. Field water condition had a strong effect on ammonia
      volatilization. Under waterlogging, both the amount of total ammonia
      volatilization and the percentage of lost fertilizer N were higher, and the
      ammonia volatilization rate increased with increasing N application rate, being
      significantly different among different N levels (P < 0.05). Under un
      waterlogging, the ammonia volatilization was relatively low. N application rate
      and the ammonium concentration and pH in surface water were the main factors
      affecting ammonia volatilization, while P application rate had little effect when
      the N application rate was 180 kg N x hm(-2).

PMID- 18333454
TI  - [Characteristics of nitrous oxide flux in spring wheat field ecosystem in
      Sanjiang Plain of Northeast China].
AB  - With static-closed-chamber and GC (Agilent 4890), the nitrous oxide (N2O) flux in
      spring wheat field ecosystem in the Sanjiang Plain of Northeast China was
      continuously observed in situ from May 2004 to October 2006. The results showed
      that the N2O flux presented obvious seasonal and inter-annual variation, which
      was mainly related with precipitation and field water management. The diurnal
      variation of N2O flux had correlations with the air temperature and the
      temperature at 5 cm underground. Wheat field ecosystem was the strong sources of
      atmosphere N2O during plant growth season. The N2O flux decreased obviously in
      fallowing period, was weaker in freezing period, and increased slowly when soil
      thawing. The average N2O flux in wheat growth season was 0.190 mg x m(-2) x h(
      1), the flux was 0.077 mg x m(-2) x h(-1) from after-reaping to before-freezing
      period, and 0.017 mg x m(-2) x h(-1) in freezing and thawing period.

PMID- 18333455
TI  - [Effects of vegetation recovery practices on the characteristics of soil nematode
      communities on seriously degraded grasslands in Songnen Plain].
AB  - In this paper, the data of soil nematodes on the seriously degraded grasslands in
      Songnen Plain under different vegetation recovery practices were collected from
      May to October, 2005, and the community structure and its seasonal changes of the
      nematodes were studied by using the community parameters of generic richness,
      abundance, diversity index, and functional group index. The results showed that
      both fencing enclosure and planting Puccinellia chinampoensis could improve the
      nematode communities substantially. The nematode abundance and diversity were
      significantly higher in planting P. chinampoensis than in fencing enclosure,
      whereas the generic richness and evenness had no significant difference between
      these two vegetation recovery practices. The functional group index indicated
      that fencing enclosure and planting P. chinampoensis altered the ratio of rho-
      and kappa- choice of plant parasite nematodes. Compared with free-living
      nematodes, plant parasite nematodes were more sensitive to the vegetation
      recovery practices. On the seriously degraded grasslands in Songnen Plain,
      planting P. chinampoensis could be more favorable to the restoration of soil
      nematode communities than fencing enclosure.

PMID- 18333456
TI  - [Effects of applying Sophora alopecuroids extracts and emamectin on the growth,
      development, and fecundity of diamondback moth plutella xylostella].
AB  - In this paper, the methanol- and water extracts of Sophora alopecuroids were
      applied respectively with emamectin, to study their effects on the growth,
      development, and fecundity of diamondback moth Plutella xylostella. The results
      showed that the oral toxicity of the mixtures to the 3rd larvae of P. xylostella
      was much higher than that of emamectin, with the medium lethal concentration
      (LC50) of methanol extract plus emamectin, water extract plus emamectin, and
      emamectin being 0.19, 0.32 and 0.51 mg L(-1), respectively. The pupated
      percentage, emergence percentage, and fecundity of P. xylotella were obviously
      negatively affected after treated the 3rd larvae with sub-lethal dosage of the
      mixtures and emamectin.

PMID- 18333457
TI  - [Screening, identification, and antagonism assessment, of dominant bacteria in
      Ageratina adenophora Sprengel rhizosphere soil].
AB  - By using isolation and culture method, 25 strains of dominant bacteria in
      Ageratina adenophora rhizosphere soil were isolated and identified, of which, 8
      strains were assessed for their antagonistic activity. The results showed that
      Bacillus and Pseudomonas were highly abundant in A. adenophora rhizosphere soil,
      of which, B. subtilis and B. megaterium were most abundant and occupied 55.6% of
      the total identified bacteria. These dominant bacteria had different level
      antagonistic activity to Fusarium oxysporum and Ralstonia solanacearum, and B.
      subtilis BS-5 and B. thuringiensis BT-1 had the strongest antagonistic effect on
      F. oxysporum, with the antagonistic activity of their metabolic products being
      85.5% and 83.8%, respectively. The metabolic products of the dominant
      antagonistic bacteria had even more stronger antagonistic effect on pathogens
      than the dominant antagonistic bacteria themselves. The existence of abundant
      bacterial groups with strong antagonistic activity in A. adenophora rhizosphere
      soil could help A. adenophora to resist harmful soil-borne diseases and escape
      its natural enemies. Through the feedback actions of the beneficial rhizosphere
      microbes, A. adenophora probably earned its competition superiority directly or
      indirectly, being favorable to its rapid expansion.

PMID- 18333458
TI  - [Optimization of biotransformation conditions of active component in Panax
      notoginseng stalks and leaves by Fusarium sacchari].
AB  - By using Fusarium sacchari, a rare microbial strain isolated and screened from
      planted ginseng soil, the active component notoginseng triterpenes in Panax
      notoginseng stalks and leaves was biotransformed. Taking three main anti-tumor
      components, i. e., 20 (S)-protopanoxadiol-20-O-beta-D-glucopyranose (compound K,
      C-K), 20-O-beta-D-xylopyranosyl (1 --> 6) -beta-D-glucopyranosyl-20 (S)
      protopanaxadiol (compound Mx, C-Mx) and 20 (S)-protopanoxadiol-20-O-alpha-L
      arabofuranose (1 --> 6)-beta-D-glucopyranose (ginseng Mc, G-Mc) as evaluation
      indices, the optimization of biotransformation conditions of notoginseng
      triterpenes in P. notoginseng stalks and leaves were obtained by factor
      biotransformation experiment, i. e., initial pH value 6, substrate addition 40
      mg, medium volume 30 ml, and transforming for 6 days at 30 degrees C. The method
      could increase the utility and economic benefit of P. notoginseng stalks and
      leaves effectively.

PMID- 18333459
TI  - [Population expansion of Spartina alterniflora and Phragmites australis at
      Jiuduansha, Shanghai based on cellular automata model].
AB  - Based on the field survey and the interpretation and analysis of satellite images
      about the population expansion patterns of Spartina alterniflora and Phragmites
      australis at Jiuduansha shoals in 1997-2004, and combined with 3S techniques, a
      cellular automata (CA) model was built to simulate the population dynamics of
      plants adaptable to salt marsh. The results showed that the model could well
      simulate the population expansion pattern and trend of S. alterniflora and P.
      australis at Jiuduansha, and strongly supported the hypothesis of space pre
      emption and range expansion with simple advancing wave fronts of these two
      species. The native species P. australis shared the same niche with the exotic
      species S. alterniflora, but the range expansion rate of S. alterniflora was 2-4
      times faster than that of P. australis. With the accretion of the Jiuduansha
      shoals, a rapid range expansion of S. alterniflora was predicted to last for a
      long period in the future. The CA model built in this study could gain valuable
      insights into the relationships between population expansion pattern and its
      ecological processes of exotic plant species, and was of significance for wetland
      biodiversity conservation and resources management.

PMID- 18333460
TI  - [Morphological characteristics and spatial heterogeneity of Nitraria sphaerocarp
      nebkhas in desert-oasis ecotone].
AB  - Taking the desert-oasis ecotone in Jinta and Linze of Gansu Province as study
      area, this paper studied the morphological characteristics of Nitraria
      sphaerocarp Nebkhas in the habitats of Gobi and desert, with the relationships
      among the morphological parameters, spatial pattern, and spatial heterogeneity
      analyzed quantitatively. The results showed that the N. sphaerocarp nebkhas was
      of convex and independent type, and obviously wind-eroded in Jinta. The average
      values of N. sphaerocarp nebkhas's height, volume, and plant canopy diameter were
      1.43 m, 65.19 m3 and 94.06 m2, respectively, being larger in desert than in Gobi,
      and the maximum values were in Jinta's desert. The average values of the plant
      height and coverage in Linze desert were larger than those in Gobi, while those
      in Jinta were in adverse, with their maximum values being 0.48 m and 0.55,
      respectively. There were significant linear relationships between the long axis
      and short axis, and between the volume and plant canopy diameter of the nebkhas.
      The relationships between the height and area, and between the volume and plant
      canopy diameter were both linear. N. sphaerocarp nebkhas showed zonary
      distribution and patchy patterns along interdune. The spatial correlation of
      nebkhas in the Gobi of Jinta and Linze was comparatively strong, while that in
      Jinta's desert was moderate. There was the possibility that the spatial
      heterogeneity was chiefly resulted by the stochastic reason in Linze's desert.
      The spatial heterogeneity of N. sphaerocarp nebkhas was mostly derived from the
      variation formed by the structural reason. The spatial heterogeneity was the
      highest in Linze's Gobi and the lowest in Linze's desert, while that in Jinta's
      Gobi and desert was between the formers.

PMID- 18333461
TI  - [Urban landscape functional regionalization and development strategy in Shenyang
      City].
AB  - According to the topography, land type suitability and human activity, the urban
      area of Shenyang City was regionalized into four landscape functional regions,
      i.e., economic and cultural supporting region, ecological equilibrium region
      (including northern high plain equilibrium sub-region and southern low plain
      equilibrium sub-region), ecological supporting region (including eastern
      ecological supporting sub-region and western ecological supporting sub-region),
      and ecological barrier region. In economic and cultural supporting region, the
      radiation of function in economy and culture should be strengthened, and the
      natural and artificial green space system should be preserved. In ecological
      supporting region, environmentally friendly industries should be developed to
      provide diverse ecological service well. As a combination of natural and man-made
      ecological system, the ecological equilibrium region could balance and steady the
      other regional services. To keep the balance between artificial and natural
      landscapes in this region, it was needed to control the expansion of construction
      land, maintain the natural and semi-natural system, and build the ecological
      corridors to connect various natural system. In ecological barrier region, the
      ecological environment was in instability, where the protection and production
      should be dealt with equally.

PMID- 18333462
TI  - [Spatial scale effect of urban land use landscape pattern in Shanghai City].
AB  - Based on geographic information system (GIS) and remote sensing (RS) techniques,
      the landscape classes of urban land use in Shanghai City were extracted from SPOT
      images with 5 m spatial resolution in 2002, and then, the classified data were
      applied to quantitatively explore the change patterns of several basic landscape
      metrics at different scales. The results indicated that landscape metrics were
      sensitive to grain- and extent variance. Urban landscape pattern was spatially
      dependent. In other words, different landscape metrics showed different responses
      to scale. The resolution of 40 m was an intrinsic observing scale for urban
      landscape in Shanghai City since landscape metrics showed random characteristics
      while the grain was less than 40 m. The extent of 24 km was a symbol scale in a
      series of extents, which was consistent with the boundary between urban built-up
      area and suburban area in Shanghai City. As a result, the extent of 12 km away
      from urban center would be an intrinsic handle scale for urban landscape in
      Shanghai City. However, due to the complexity of urban structure and asymmetry of
      urban spatial expansion, the intrinsic handle scale was not regular extent, and
      the square with size of 24 km was just an approximate intrinsic extent for
      Shanghai City.

PMID- 18333463
TI  - [Spatial correlation between non-agricultural land expansion and soil quality in
      Suzhou City].
AB  - Based on the layer of non-agricultural land expansion interpreted from 4 Landsat
      TM images in 1984, 1995, 2000 and 2003 and the soil quality map, the patterns of
      non-agricultural land expansion occurring on soil quality levels in Suzhou City
      were analyzed. It was indicated that the non-agricultural land expansion happened
      mainly on the soils with high quality during 1984-2003. 90% of the expansion took
      place on the soils with moderately high quality (grade 2), and the next was those
      with high quality (grade 1). In the meanwhile, the expansion on the soils with
      moderate (grade 3) and low quality (grade 4) was only less than 1% of total area.
      From the viewpoint of soil quality, we should ponder more over the opinion on
      "dynamic balance of total amount of arable land between occupying and
      supplementing".

PMID- 18333464
TI  - [Landscape change in upper reaches of Minjiang River].
AB  - Based on the fuzzy logic knowledge database designed by NetWeaver tools, and
      using ecosystem management decision support system (EMDS), a quantitative
      evaluation was made on the landscape change in the upper reaches of Minjiang
      River from 1986 to 2000. The results showed that the type, area, amount, and
      spatial distribution of landscape patches in the reaches changed greatly, and the
      changing direction was in favor of ecosystem restoration. The changes of forest
      landscape mainly occurred in the north part of study area (Songpan County and
      Heishui County), while those of grass landscape mainly occurred both in the north
      part and in the furthest south part (Wenchuan County). The joint effect of
      increasing human activities and nature change was the driving force of the
      landscape changes.

PMID- 18333465
TI  - [Regional eco-security assessment of southwest Beijing].
AB  - Based on the zoning regulation which integrated climate, vegetation and soil as a
      complex, a regional eco-security index system consisting of regional physical
      background, ecosystem stability, landscape structure, and external interference
      was established, and, with the support of geographical information system
      technology and fuzzy mathematics, a set of regional eco-security assessment
      methods was constructed. By means of these methods, the eco-security index of
      southwest Beijing in 2004 was calculated based on the recent 30 years background
      data of climate and soil. The results showed that in southwest Beijing, the eco
      security degree was higher in its central area and western hilly-shallow hilly
      areas, but lower in its southern and southeastern plain areas. The mining
      activity in southwest Beijing had threatened the environment, and should be
      stopped immediately to maintain the regional eco-security. It was proved in the
      case study that the assessment index system and related methods established in
      this paper could solve the existing problems in assessing regional eco-security,
      and the assessment results could reflect the regional ecological issues and the
      status of eco-security at different locations within the region.

PMID- 18333466
TI  - [Regional characteristics of sulfur contents in flue-cured tobacco in Hunan
      Province and their influence to smoking quality].
AB  - A total of 559 flue-cured tobacco samples with 3 grades (B2F, C3F and X2F) were
      collected from the main tobacco-growing areas in Hunan Province, and their sulfur
      contents were determined to study the regional characteristics of the sulfur
      contents and their quantitative correlations with the evaluation indices of
      smoking quality. The results showed that the sulfur content in the flue-cured
      tobacco was 0.100%-2.106% , with a mean of 0.884%. The samples with sulfur
      content above 0.7% accounted for 71.56% of the total. The sulfur content
      decreased gradually from the high sulfur content area of Central Hunan to South
      Hunan and Northwest Hunan. With increasing sulfur content in tobacco leaf, the
      aroma quality, aftertaste, combustibility and ash color went to bad, offensive
      odor and irritation property increased, and aroma taste, eat-taste and total
      smoking quality score fell down. Under the influence of applying larger amount
      sulfate potassium and of sulfur-type acid precipitation, the sulfur content in
      tobacco leaf was somewhat higher in partial areas of Hunan Province, and gave
      negative impact on tobacco quality, being one of key factors limiting the
      improvement of tobacco quality and ought to be attached enough importance in
      tobacco production.

PMID- 18333467
TI  - [DNA fingerprinting structure of plankton community and its relations to
      environmental physical-chemical factors in Donghu Lake].
AB  - By the method of RAPD fingerprinting, this paper studied the DNA fingerprinting
      structure of plankton community and its relations to the main environmental
      physical-chemical factors at five sites in Donghu Lake. From the screened 9
      random primers, a total of 210 observable bands with a length of 150-2 000 bp
      were amplified, 93.3% of which were polymorphic. At the five sites, the average
      number of amplified bands was 42, with the maximum (53) at site IV and the
      minimum (35) at site V. The PO4(3-)-P and TP contents were the highest at site I,
      NH4(+)-N, TN and NO2(-)-N contents were the highest at site V, while the values
      of all test physical-chemical parameters were the lowest at site IV. No obvious
      differences in COD, alkalinity, rigidity, and calcium content were observed among
      the study sites. Similarity clustering analysis showed that the DNA
      fingerprinting of plankton community based on RAPD marker could cluster the five
      sites into two groups, i. e., sites I, II and III could be clustered into one
      group, while sites IV and V could be clustered into another group, which was
      consistent with the clustering analysis based on the main environmental physical
      chemical factors. In conclusion, there was a close relation between the DNA
      fingerprinting structure of plankton community and the main environmental
      physical-chemical factors in Donghu Lake.

PMID- 18333468
TI  - [Effects of red tide microalgae Alexandrium tamarense on the life history of
      rotifer Brachionus plicatilis].
AB  - In this paper, life-table method was used to study the effects of different
      concentration Alexandrium tamarense on the durations of different development
      stages of Brachionus plicatilis and the characters of its population growth. The
      results showed that A. tamarense had significant effects on the growth and
      development of B. plicatilis via prolonging the durations of the rotifer' s pre
      reproduction and generation succession, shortening the durations of its
      reproduction and post-reproduction and its mean lifespan, and reducing its laying
      eggs and fecundity. The net reproduction rate and intrinsic increasing rate of B.
      plicatilis decreased significantly, in comparison with those of the control. B.
      plicatilis could maintain definite population increase at the presence of
      different concentration A. tamarense.

PMID- 18333469
TI  - [Effects of suspended matter concentration in water body on the spectral
      reflectivity of submersed plant Hydrilla verticillata].
AB  - To restore submersed aquatic vegetation has been recognized as an effective
      measure in improving eutrophicated water bodies and reestablishing aquatic
      ecosystems. Remote sensing technology can be used to timely monitor the
      distribution and growth status of submersed vegetation on a large scale, but the
      suspended matter in water bodies may affect the spectral characters of submersed
      vegetation, resulting in an inaccuracy of the interpretation of related remote
      sensing images. In this study, the spectral reflectivity of submersed plant
      Hydrilla verticillata in the water bodies with different suspended matter
      concentration was measured by a ground FieldSpec Pro JR spectroradiometer, and
      the results showed that the spectral reflectivity of the submersed plant
      increased with increasing concentration of suspended matter at the band of 400
      900 nm. Significant correlations were observed between the suspended matter
      concentration and the spectral reflectivity of H. verticillata community at the
      band of 400-900 nm (P < 0.05) and of 450-900 nm (P < 0.01), and a clear linear
      relationship was found at the wavelength bands of blue, green, red and NIR. The
      results obtained in this study could be used to calibrate the effects of
      suspended matter in water body on the spectral reflectivity of submersed
      vegetation, and be helpful to rapidly and accurately monitor the distribution and
      dynamics of submersed vegetation on a large scale with remote sensing.

PMID- 18333470
TI  - [Development and allometric growth patterns of larval Acipenser schrenckii].
AB  - The growth and development of larval Amur sturgeon Acipenser schrenckii could be
      divided into two stages, i.e., pre-larval or free embryonic stage [from hatching
      (0 day of age and 10.17 +/- 0.63 mm of body length) to initial feeding (9 days of
      age and 18.93 +/- 0.74 mm of body length)], and post-larval stage [from initial
      feeding to juvenile stage (38 days of age and 41.89 +/- 5.09 mm of body length)].
      During pre-larval stage, some organs related to feeling, feeding, breathing and
      swimming developed and differentiated rapidly; and during post-larval stage,
      dorsal, lateral and ventral scuta appeared, and the fish morphologically
      developed into juvenile. The growth characteristics of larval A. schrenckii
      presented allometric patterns, i.e., the growth inflexion points of eye diameter,
      mouth width, tail fin length, and pectoral fin length appeared in the ages of 2
      days, 8-9 days, 10 days, and 11 days, respectively. Before the growth inflexion
      points, the organs grew fast; while after the growth inflexion points, the growth
      slowed down and approximately appeared isometric. The organs of larval A.
      schrenckii had the characteristics of congruous and rapid development. With the
      development of the organs related to feeling, feeding, breathing and swimming,
      larval A. schrenckii obtained the ability of escaping from predators and feeding,
      and consequently, its survival chance increased.

PMID- 18333471
TI  - [Life history characteristics of different genotype clones of Brachionus
      calyciflorus (Rotifera) population in Jinghu Lake].
AB  - By means of life table demographic approach, the life-table demographic
      parameters and the percentage of mictic females in the offspring of thirteen
      genetically different Brachionus calyciflorus clones were studied at 15 degrees
      C, 20 degrees C, 25 degrees C and 30 degrees C. The results showed that the
      responses of the generation time, average lifespan, life expectancy at hatching,
      intrinsic rate of population increase, net reproductive rate, and percentage of
      mictic females in the offspring of B. calyciflorus to increasing temperature
      differed with rotifer clones. Temperature, clone, and their interaction
      influenced the life-table demographic parameters and the percentage of mictic
      females in the offspring of B. calyciflorus significantly. The temporal
      heterogeneity of water temperature could be one of the reasons for the high
      genetic diversity in B. calyciflorus population in Jinghu Lake. Natural selection
      occurred in coexisting clones, and its function might be too weak or too time
      limited to make the clonal exclusion occur. Genetic drift might play an important
      role in genotype frequency variation. The coexistence of different genotype
      clones of B. calyciflorus population is of significance for the existence of the
      population in water environment.

PMID- 18333472
TI  - [Forest litter decomposition and its responses to global climate change].
AB  - Litter decomposition is one of the important processes in forest ecosystem, which
      is controlled by both biotic and abiotic factors such as climate, litter quality,
      and soil organisms. Up to now, numerous studies have been made on the dynamics of
      aboveground litter in different forest ecosystems, nutrient release during its
      decomposition, and effects of biotic and abiotic factors on the decomposition,
      but less information has been reported on the decomposition of belowground forest
      litter. Recently, the responses of forest litter decomposition to global climate
      change characterized by elevated atmospheric CO2 concentration and temperature
      have got worldwide concern, but there remains uncertainty in research results. In
      the further study, more attention should be paid on the contribution of forest
      litter decomposition to soil organic carbon sequestration, the physical, chemical
      and biological processes of below- and above-ground litter decomposition, the
      responses of forest litter decomposition to the ecological factors (e.g. seasonal
      freeze-thaw cycle and drying-rewetting cycle) and their interactions, and the
      mechanisms of litter (especially belowground litter) decomposition responses to
      global climate change.

PMID- 18333473
TI  - [Responses of soil organic carbon and nitrogen decomposition to changing
      temperature and related research methods: a review].
AB  - In this paper, the researches about the relationships of soil carbon and nitrogen
      storage with temperature, and the responses of soil carbon and nitrogen
      decomposition to the spatiotemporal differentiation of temperature, increasing
      air temperature, and soil freezing-thawing were summarized, and the uncertainty
      and determination errors of related research methods were discussed. Climate
      warming could promote soil carbon and nitrogen decomposition and soil CO2
      emission within a short period, but not always accelerate the decomposition of
      soil carbon and nitrogen in a long-term. Therefore, to give a reasonable
      interpretation on the discrepancies of previous studies, a systematic analysis on
      the mechanisms about the effects of changing temperature on the decomposition of
      soil carbon and nitrogen should be made, and the differences about the long-term
      and short-term responses of soil carbon and nitrogen decomposition to the
      changing temperature, as well as the influences of research method, vegetation,
      soil, and climate conditions on the research results should also be fully
      understood.

PMID- 18333474
TI  - [Water and soil conservation function of typical plantation forest ecosystems in
      semi-arid region of Western Liaoning Province].
AB  - From the aspects of surface runoff and soil erosion, this paper quantitatively
      studied the water and soil conservation function of five plantation forest
      ecosystems in semi-arid region of Western Liaoning Province. The results showed
      that various types of test plantation forest ecosystems were all able to reduce
      surface runoff and soil erosion effectively. In June - September, the monthly
      mean surface runoff coefficient of Pinus tabulaeformis forest ecosystem, P.
      tabulaeformis - Hippophae rhamnoides forest ecosystem, H. rhamnoides forest
      ecosystem, P. simonii forest ecosystem, and P. simonii - H. rhamnoides forest
      ecosystem was 10.1%, 6.5%, 2.3%, 8.6% and 5.3% of that of barren hill,
      respectively, and the soil erosion quantity was 2.65%, 0.96%, 0.15%, 2.32% and
      0.69% of that of barren hill, respectively. Among the five forest ecosystems, H.
      rhamnoides forest ecosystem had the least surface runoff and soil erosion, being
      the best in water and soil conservation function.

PMID- 18333476
TI  - [Characteristics of contemporary landscape ecology: analysis based on the 7th
      IALE World Congress].

PMID- 18333475
TI  - [Insecticidal activity and active components of alcohol extract from Juglans
      mandshurica Maxim leaves].
AB  - The insecticidal active components in Juglans mandshurica Maxim leaves were
      extracted by conventional method. The alcohol extract and its chloroform
      extraction phase showed insecticidal activities in contact toxicity and stomach
      toxicity against Lymantria dispar L. and Mamestra brassicae L. larvae. When the
      concentration of the extract was above 10 g x L(-1), the corrected mortality was
      higher than 50% 5 days after applying the extract. Alcohol extract had higher
      insecticidal activities than its chloroform-extraction phase. The GC-MS analysis
      on the active components in the chloroform-extraction phase showed that the main
      component was juglone (5-hydroxy-1,4-naphthalenedione), and the others were 2,2'
      methylenebis-6-(1,1-dimethylethyl)-4-methyl-diphenol and 2-methoxy-4-vinylphenol.

PMID- 18333477
TI  - Multitiered health assessment of Atlantic menhaden in the Pamlico River, North
      Carolina.
AB  - During the fall of 2001 and 2002, Atlantic menhaden Brevoortia tyrannus were
      collected from several creeks in the Pamlico River, North Carolina, to
      investigate recent fish kills and ulcerative skin lesions. High skin lesion
      prevalence (>50%) was associated with the Atlantic menhaden kills in fall 2001,
      whereas there were no fish kills in fall 2002 and skin lesion prevalence was
      lower (< or =50%). Indicators of tissue damage (histopathological analyses of
      gills, heart, liver, intestine, and anterior kidney), body condition (liver
      somatic index), and immune status (transforming growth factor-beta [TGF-beta]
      messenger RNA [mRNA] production, hematology, plasma chemistry, and splenosomatic
      index) were compared between Atlantic menhaden with and without ulcerative skin
      lesions in fall. Atlantic menhaden with ulcerative skin lesions had significantly
      higher liver somatic indices, neutrophil and monocyte percentages, and splenic
      mononuclear cell TGF-beta mRNA levels than did fish without lesions. Hematocrit
      values, plasma protein, and Ca concentrations were significantly lower in fish
      with ulcerative skin lesions than in those without. The indicators used in this
      study at multiple levels of biological organization have provided valuable
      baseline data for understanding the health status of lesioned and nonlesioned
      Atlantic menhaden in the Pamlico River.

PMID- 18333478
TI  - Host susceptibility hypothesis for shell disease in American lobsters.
AB  - Epizootic shell disease (ESD) in American lobsters Homarus americanus is the
      bacterial degradation of the carapace resulting in extensive irregular, deep
      erosions. The disease is having a major impact on the health and mortality of
      some American lobster populations, and its effects are being transferred to the
      economics of the fishery. While the onset and progression of ESD in American
      lobsters is undoubtedly multifactorial, there is little understanding of the
      direct causality of this disease. The host susceptibility hypothesis developed
      here states that although numerous environmental and pathological factors may
      vary around a lobster, it is eventually the lobster's internal state that is
      permissive to or shields it from the final onset of the diseased state. To
      support the host susceptibility hypothesis, we conceptualized a model of shell
      disease onset and severity to allow further research on shell disease to progress
      from a structured model. The model states that shell disease onset will occur
      when the net cuticle degradation (bacterial degradation, decrease of host immune
      response to bacteria, natural wear, and resorption) is greater than the net
      deposition (growth, maintenance, and inflammatory response) of the shell.
      Furthermore, lesion severity depends on the extent to which cuticle degradation
      exceeds deposition. This model is consistent with natural observations of shell
      disease in American lobster.

PMID- 18333479
TI  - Quantitative polymerase chain reaction assay for largemouth bass virus.
AB  - The use of quantitative polymerase chain reaction (QPCR) to test for largemouth
      bass virus (LMBV) was evaluated during a challenge experiment in which largemouth
      bass Micropterus salmoides were immersed in the type strain of LMBV. The real
      time PCR and cell culture methods were both used to measure LMBV present in the
      inoculum. Additional samples tested by QPCR included gill, gonad, kidney, liver,
      mucus, spleen, and swim bladder. A plasmid clone containing a 248-base pair (bp)
      fragment of the major capsid protein gene (MCP*) was serially diluted and used as
      a standard to quantify the number of LMBV DNA copies present in the samples
      tested. A 62-bp fragment of DNA located in MCP* was amplified in the real-time
      PCR assay. This work has demonstrated the value of the QPCR assay in LMBV
      surveys.

PMID- 18333480
TI  - A packed-bed filtration system for collection of Myxobolus cerebralis
      triactinomyxons.
AB  - Information on the distribution and abundance of Myxobolus cerebralis
      triactinomyxons in natural systems is limited because direct and accurate
      sampling methods for this life stage have not been developed. Existing methods
      are based on indirect measures of triactinomyxon densities and are therefore
      confounded. Direct estimation of triactinomyxon concentrations would more exactly
      pinpoint the ambient infection risk to wild fish and allow evaluation of
      management strategies designed to mitigate the effects of the disease. We
      developed a mobile packed-bed filtration system that quickly, accurately, and
      precisely collects, concentrates, and quantifies triactinomyxons. The system
      includes pumping, prefiltration, two rounds of packed-bed filtration, and
      centrifugation. Laboratory tests of the completed system using known quantities
      of triactinomyxons resulted in a mean recovery rate of 91% with a minimum
      detectable concentration of triactinomyxons of 0.04/L. We subsequently field
      tested the system at a site known to be positive for the parasite and recovered
      triactinomyxons at densities of 0.7-1.4/L. The packed-bed filtration system has
      the potential to quickly determine the temporal and spatial variation in
      infection risk and to test the efficacy of various management strategies.

PMID- 18333481
TI  - Intersex (testicular oocytes) in smallmouth bass from the Potomac River and
      selected nearby drainages.
AB  - Intersex, or the presence of characteristics of both sexes, in fishes that are
      normally gonochoristic has been used as an indicator of exposure to estrogenic
      compounds. In 2003, during health assessments conducted in response to kills and
      a high prevalence of skin lesions observed in smallmouth bass Micropterus
      dolomieu in the South Branch of the Potomac River, the presence of immature
      oocytes within testes was noted. To evaluate this condition, a severity index (0
      4) was developed based on the distribution of oocytes within the testes. Using
      gonad samples collected from 2003 to 2005, the number of histologic sections
      needed to accurately detect the condition in mature smallmouth bass was
      statistically evaluated. The reliability of detection depended on the severity
      index and the number of sections examined. Examining five transverse sections
      taken along the length of the gonad resulted in a greater than 90% probability of
      detecting testicular oocytes when the severity index exceeded 0.5. Using the
      severity index we compared smallmouth bass collected at selected sites within the
      South Branch during three seasons in 2004. Seasonal differences in severity and
      prevalence were observed. The highest prevalence and severity were consistently
      noted during the prespawn-spawning season, when compared with the postspawn
      season. In 2005, smallmouth bass were collected at selected out-of-basin sites in
      West Virginia where fish kills and external skin lesions have not been reported,
      as well as at sites in the Shenandoah River, Virginia (part of the Potomac
      drainage), where kills and lesions occurred in 2004-2005. The prevalence of
      testicular oocytes is discussed in terms of human population and agricultural
      intensity.

PMID- 18333482
TI  - Genetic diversity of infectious hematopoietic necrosis virus from Feather River
      and Lake Oroville, California, and virulence of selected isolates for Chinook
      salmon and rainbow trout.
AB  - Infectious hematopoietic necrosis virus (IHNV) is a significant pathogen of young
      salmonid fishes worldwide but particularly within the historical range of the
      Pacific Northwest and California. In the Sacramento and San Joaquin River
      drainages of California, IHNV outbreaks in juvenile Chinook salmon Oncorhynchus
      tshawytscha have been observed regularly at large production hatcheries,
      including Coleman National Fish Hatchery (established in 1941) and Feather River
      State Fish Hatchery (FRH; established in 1967), since facility operations began.
      Recent severe epidemics at the FRH in 1998 and 2000-2002 prompted investigations
      into the characteristics and potential sources of virus at this facility. Both
      phylogenetic analyses of a variable portion of the glycoprotein gene and
      serologic comparisons based on neutralization with three polyclonal rabbit sera
      were used to characterize 82 IHNV isolates from the Feather River watershed
      between 1969 and 2004. All isolates examined were in the L genogroup and belonged
      to one of three serologic groups typical of IHNV from California. The IHNV
      isolates from the Feather River area demonstrated a maximum nucleotide sequence
      divergence of 4.0%, and new isolates appeared to emerge from previous isolates
      rather than by the introduction of more diverse subgroups from exogenous sources.
      The earliest isolates examined from the watershed formed the subgroup LI, which
      disappeared coincidently with a temporal shift to new genetic and serologic types
      of the larger subgroup LII. Experimental challenges demonstrated no significant
      differences in the virulence for juvenile Chinook salmon and rainbow trout O.
      mykiss from selected isolates representing the principal types of IHNV found
      historically and from recent epidemics at FRH. While most isolates were equally
      virulent for both host species, one isolate was found to be more virulent for
      Chinook salmon than for rainbow trout.

PMID- 18333483
TI  - Parasite survey of the eastern oyster Crassostrea virginica in coastal lagoons of
      the southern Gulf of Mexico.
AB  - A parasitological study of the eastern oyster Crassostrea virginica from 11
      coastal lagoons in the southern Gulf of Mexico in dry and rainy seasons between
      late 1999 and early 2001 revealed the presence of 36 bacterial, 2 protozoan
      (Nematopsis prytherchi and Perkinsus marinus), and 4 helminth species (Urastoma
      cyprinae, Proctoeces maculatus, a Bucephalus sp., and a Tylocephalum sp.). The
      prevalence and mean abundances for the protozoa and helminths varied widely
      between locations but were generally below 50%. Nematopsis prytherchi and the
      Tylocephalum sp. were the most prevalent species (values were above 60% in most
      locations). Perkinsus marinus was present in oysters of eight of the coastal
      lagoons and had low prevalence (<30%) in almost all samples. All identified
      protozoa and helminths are widely distributed in the Gulf of Mexico and are
      common oyster parasites. Only P. marinus and the Bucephalus sp. were associated
      with damage to host tissues. In addition to these parasites, Rickettsia-like
      bacteria were found in the digestive gland and gills and viral gametocytic
      hypertrophy inclusions in the gonads by histological examination.

PMID- 18333484
TI  - Should asthmatics be enlisted?

PMID- 18333485
TI  - The emerging role of preventive medicine in health diplomacy after the 2005
      earthquake in Pakistan.
AB  - On October 22, 2005, a preventive medicine team deployed with the 212th Mobile
      Army Surgical Hospital to assist with earthquake relief efforts in Pakistani
      controlled Kashmir. These efforts included core field preventive medicine but
      quickly extended into other efforts. In collaboration with the host nation and
      other organizations, the preventive medicine team performed additional support
      for operations outside the U.S. compound, including water and sanitation
      assessments of camps for internally displaced persons, communicable disease
      investigation and control, and vaccination programs. Preventive medicine
      personnel were vital to health diplomacy efforts in this operation, particularly
      because of security concerns that prevented other U.S. medical assets from
      leaving the compound. Comparisons with the U.S. responses during other
      humanitarian operations are made. Preventive medicine missions in health
      diplomacy will continue to increase. Training and collaborative relationships
      with other government agencies, such as the U.S. Agency for International
      Development, and with nongovernmental organizations should continue to be
      developed.

PMID- 18333486
TI  - The Joint Medical Workstation (JMeWS) database in 2003: intradeployment health
      encounters of military personnel supporting Operations Enduring Freedom and Iraqi
      Freedom.
AB  - The Joint Medical Work Station (JMeWS) is a theater medical surveillance system
      that integrates information from three separate health data collection systems
      for the Army, Navy, Air Force, and Marines. Our objective was to characterize
      JMeWS data during its first year of implementation in 2003. We conducted a
      descriptive analysis of health events documented in JMeWS among military
      personnel deployed to Operations Enduring Freedom and Iraqi Freedom. Among the
      38,498 individuals (7.8%) with a JMeWS record, women, college-educated, older
      individuals, and Reserve/Guard personnel were over-represented. There was wide
      variability by service (Air Force, 25%; Army, 5.5%; Marine Corps, 1.2%; and Navy,
      0.6%). The most common diagnoses were in the categories of injury and poisoning,
      respiratory conditions, and musculoskeletal disorders. Differences in
      distribution of the various patient encounter modules in theater likely resulted
      in variable data capture across services. System enhancements should improve
      future applications.

PMID- 18333487
TI  - Investigation of the operational effectiveness of Hunter Company, Commando
      Training Centre, Royal Marines.
AB  - The aim of the study was to investigate the operational effectiveness of Hunter
      Company, Commando Training Centre Royal Marines (RM) in rehabilitating injured RM
      recruits, through the collection of demographic, medical, and performance data
      for 1 year's intake of RM recruits (N=1115). Flow models for progression through
      mainstream training and through Hunter Company were developed. The data were
      analyzed to determine the week of training in which different injuries occurred
      and the duration and outcome of rehabilitation. Sixty prcent of ex-Hunter Company
      recruits were successfully returned to mainstream training and graduated
      successfully. Given that the median number of weeks in training before injury was
      24 and the median time taken to recover from an injury was 14 weeks, it is more
      effective to rehabilitate a recruit in Hunter Company than to discharge him and
      replace him with a new recruit.

PMID- 18333488
TI  - Concerns about career stigma by military parents of children with psychiatric
      illness.
AB  - Stigma is known to have deleterious effects on individuals with psychiatric
      disorders as well as their family members. In this study, we examined stigma with
      regard to career concerns among active duty members of the Air Force with
      children who have psychiatric disorders. Albeit a weak relationship, a bivariate
      correlation confirmed a significant relationship between the child's mental
      health utilization (i.e., severity of illness) and participants concerns about
      the potential effects on their military (r = 0.423, p < 0.01), as well as
      civilian (r = 0.353, p < 0.01), careers. These findings indicate that among
      military members with children who have psychiatric disorders, illness severity
      significantly relates to concerns about the impact of stigma on careers,
      particularly military careers.

PMID- 18333489
TI  - Body mass index and disordered eating behaviors are associated with weight
      dissatisfaction in adolescent and young adult female military recruits.
AB  - OBJECTIVE: To examine factors associated with weight dissatisfaction, a risk
      factor for eating disorders, among female Marine recruits. METHODS: A diverse
      adolescent/young adult sample of 2157 female recruits completed a questionnaire
      upon entering Marine Corps training. Weight dissatisfaction was the main variable
      of interest. RESULTS: Body mass index (BMI), disordered eating history, and worry
      about meeting military "weight" were related highly to weight dissatisfaction.
      Women with BMIs near the upper limit of the Marine Corps weight standard (23.5
      kg/m2) reported the highest rates of weight dissatisfaction. Those who reported
      vomiting, binging or pill use, or being worried about "making weight" were four
      and five times, respectively, more likely to report weight dissatisfaction.
      CONCLUSIONS: New female Marine recruits with higher BMIs, disordered eating
      histories, and worries about "making weight" are significantly more likely to be
      weight dissatisfied. Such findings may identify those at risk for developing
      eating disorders when exposed to strict military weight standards.

PMID- 18333490
TI  - Childhood predictors of military fitness: a prospective, community-based, follow
      up study from age 8 to age 18.
AB  - Knowledge of the impact of childhood psychosocial problems on success in military
      service is scarce. The purpose of the study was to assess whether childhood
      psychosocial problems are associated with suitability for military service. The
      subjects were 2,622 Finnish boys born in 1981. They were first assessed with the
      Rutter parent and teacher questionnaires and self-reports (Children's Depression
      Inventory) at age 8. Their suitability for military service was assessed at age
      18. A wide range of childhood problems, especially internalizing disorders,
      predicted release from military service. All informants had predictive
      association with later suitability for military service. The majority of children
      with psychiatric problems were later estimated to be fit for military service.
      The results show a predictive association between childhood psychiatric problems
      and early adult psychosocial impairment, as estimated by the ability to serve in
      the military forces.

PMID- 18333491
TI  - Characteristics of deployed Operation Iraqi Freedom military personnel who seek
      mental health care.
AB  - INTRODUCTION: This study reports on the feasibility of using validated mental
      health screening instruments for deployed Operation Iraqi Freedom military
      personnel. METHODS: For a 3-month period in 2005, all service members (N=296) who
      initially presented to the U.S. Military Hospital Kuwait mental health clinic
      completed an intake questionnaire that gathered demographic information and
      contained validated instruments to screen for mental disorders and functional
      impairment. RESULTS: A total of 19% of the sample subjects screened positive for
      post-traumatic stress disorder-related symptoms, 35% for a major depressive
      disorder, and 11% for severe misuse of alcohol. Significant levels of distress
      and functional impairment were reported by 58% of the sample. Women represented a
      disproportionately high percentage of those presenting for care (27%).
      CONCLUSIONS: Screening instruments were well accepted and useful in detecting
      psychopathological conditions and functional impairment. Female service members
      might represent a high-risk group. These results are useful for those caring for
      service members during or after deployment.

PMID- 18333492
TI  - Lieutenant William B. Walsh: first U.S. doctor in Hiroshima after the bomb, with
      previously unpublished photographs.
AB  - Lt. William B. Walsh, then serving on a U.S. destroyer-minesweeper in the Pacific
      Theater as a ship's doctor, was the first U.S. physician on the ground in
      Hiroshima, Japan, after the atomic bomb was dropped. This is his story, gleaned
      from interviews and his own letters to his wife written while he was serving on
      the USS Ellyson. His thoughts on the war, the enemy, and the bomb and the fears
      of the probable invasion of the Japanese mainland are a reflection of the
      thoughts of many in his position in the Pacific Theater at that time. The article
      is accompanied by previously unpublished photographs Dr. Walsh took when he was
      able to go to Hiroshima after the surrender ceremony.

PMID- 18333493
TI  - Acute effects of MK63 stun device discharges in miniature swine.
AB  - OBJECTIVE: Electromuscular incapacitation (EMI) devices are being used and
      evaluated by both military and law enforcement agencies. Although the gross
      muscular response is obvious, physiological responses to these devices are poorly
      understood. We hypothesized that the intense, repetitive, muscle contractions
      evoked by EMI devices would cause dose-dependent metabolic acidosis, accompanied
      by neuromuscular or cardiac injury. METHODS: Using an approved protocol, 26
      Yucatan mini-pigs (22 experimental animals and 4 control animals) were
      anesthetized with ketamine and xylazine. Experimental animals were exposed to
      MK63 (Aegis Industries, Bellevue, Idaho) discharges over the left anterior hind
      limb for 10, 20, 40, or 80 seconds. Electrocardiograms, electromyograms, troponin
      I levels, blood gas values, and electrolyte levels were recorded before and 5,
      15, 30, and 60 minutes and 24, 48, and 72 hours after discharge. Skin, muscle,
      and nerve biopsies were taken from the shocked and contralateral sides. RESULTS:
      Core body temperature significantly decreased (1.0-1.5 degrees C) in all shocked
      animals but not in sham-treated control animals. No cardiac dysrhythmias or
      deaths were seen, and heart rate was unaffected. No clinically significant
      changes were seen in troponin I, myoglobin, or creatine kinase-MB levels. Central
      venous blood pH decreased, whereas carbon dioxide pressure and lactate levels
      increased for 60 minutes after discharge. All values returned to normal by 24
      hours after discharge, and no significant histological or electromyographic
      changes were found. CONCLUSIONS: Changes in blood chemistry were observed but
      were of little clinical significance, and no neuromuscular damage was detected.
      Therefore, within the limitations of this model, it appears that EMI can safely
      be achieved by using this device, even for lengthy periods, without causing
      significant injury.

PMID- 18333494
TI  - Infectious diseases investment decision evaluation algorithm: a quantitative
      algorithm for prioritization of naturally occurring infectious disease threats to
      the U.S. military.
AB  - Identification of the most significant infectious disease threats to deployed
      U.S. military forces is important for developing and maintaining an appropriate
      countermeasure research and development portfolio. We describe a quantitative
      algorithmic method (the Infectious Diseases Investment Decision Evaluation
      Algorithm) that uses Armed Forces Medical Intelligence Center information to
      determine which naturally occurring pathogens pose the most substantial threat to
      U.S. deployed forces in the absence of specific mitigating countermeasures. The
      Infectious Diseases Investment Decision Evaluation Algorithm scores the relative
      importance of various diseases by taking into account both their severity and the
      likelihood of infection on a country-by-country basis. In such an analysis, the
      top three endemic disease threats to U.S. deployed forces are malaria, bacteria
      caused diarrhea, and dengue fever.

PMID- 18333495
TI  - The challenge of controlling lead and silica exposures from firing ranges in a
      special operations force.
AB  - In 2000, soldiers from a Special Operations Force had airborne lead exposures 20
      to 38 times the permissible exposure limit. Their average blood lead level was
      13.9 microg/dL. Immediate implementation of pertinent Occupational Safety and
      Health Administration regulations was recommended. In 2003, investigators learned
      that the unit also used an outdoor firing range with exposures exceeding the
      permissible exposure limit. Attempts to conduct more detailed evaluations and
      control measures were hindered by frequent deployments in the unit and a strong
      commitment to realistic training. Despite these challenges, the controls
      implemented resulted in limited success. The average blood lead level in the unit
      was 6.8 microg/dL in 2005, a reduction of 51%. Proper initial range construction
      is essential to controlling lead exposures at firing ranges. Occupational health
      specialists caring for these soldiers must identify, assess, and mitigate
      exposures from firing ranges while respecting the importance of realistic
      training.

PMID- 18333496
TI  - Impact of prolonged exercise in the heat and carbohydrate supplementation on
      performance of a virtual environment task.
AB  - PURPOSE: The purpose of this investigation was to determine whether performance
      of a virtual environment (VE) task is influenced by exercise in the heat and
      carbohydrate supplementation. METHODS: Ten males completed four exercise trials
      to fatigue. During each trial, subjects cycled at a submaximal workload. Subjects
      exercised in a normal environment (NORM) and in a hot environment on different
      occasions. During exercise, subjects drank 10 mL x kg(-1) x hour(-1) of body
      weight of a 6% carbohydrate beverage (CHO) or a placebo. Subjects completed a VE
      task before, during exercise, and after fatigue. RESULTS: More failures occurred
      during placebo than CHO during exercise. The NORM CHO trial had the fewest
      failures at fatigue. More kills occurred during exercise in the NORM CHO.
      CONCLUSIONS: Performance of a VE task was negatively influenced by prolonged
      exercise and heat stress. CHO supplementation may have a positive impact on
      performance of the VE task following prolonged exercise.

PMID- 18333497
TI  - Cardiovascular disease in a forward military hospital during operation iraqi
      freedom: a report from deployed cardiologists.
AB  - BACKGROUND: No published data are available regarding cardiac evaluations in a
      forward military hospital setting. METHODS: Two cardiologists deployed in support
      of Operation Iraqi Freedom identified all of their cardiac evaluations. Patient
      demographic data, evaluations performed, outcomes, and return-to-duty rates were
      determined. RESULTS: Four hundred sixty-nine predominantly male patients were
      evaluated, with a mean age of 39 +/- 10 years. The most common reasons for
      referral were ischemic evaluation (n=283), arrhythmia/palpitations (n=83), and
      syncope (n=57). Of those referred with ischemia, the mean Framingham 10-year
      event risk calculated was low at 5.3 +/- 3.1%; 86% of military patient
      evaluations revealed no identifiable cardiovascular pathological condition, and
      patients were returned to duty. CONCLUSIONS: Cardiology support, with the
      availability of echocardiography and stress testing in the theater of operations,
      was able to provide cardiovascular consultative evaluations and management and to
      reduce rates of medical evacuations out of the theater of operations.

PMID- 18333498
TI  - Executive management education in health care at a naval medical center: a
      descriptive report.
AB  - Resource constraints in a time of conflict place particular stress on military
      medicine, especially in view of demands for medical care due to injuries.
      Effective management of health care systems and resources is essential.
      Management education of clinical leaders therefore is an excellent investment of
      time and effort. This article describes a Master's of Public Health degree
      program customized to meet the needs of the naval health care system and
      facilitate active involvement of current employees.

PMID- 18333499
TI  - San Antonio Military Medical Center integration: a case study in organizational
      leadership design.
AB  - The Defense Base Closure and Realignment Commission law of 2005 established a
      combined Army-Air Force medical center in San Antonio, Texas. The new facility is
      named the San Antonio Military Medical Center. This planned integration of two
      facilities would result in the downsizing of Wilford Hall Medical Center to a
      clinic and expansion of the nearby Brooke Army Medical Center to encompass all
      inpatient care. As part of the integration, the emergency services of both
      hospitals, to include the emergency departments, would merge under single
      leadership. As part of this case study, the proposed future organizational design
      is examined. Real and potential barriers to change are also indentified and
      possible solutions are explored.

PMID- 18333500
TI  - Analysis of after-action reporting by deployed nurses.
AB  - The purpose of this study was to explore the nature of information in after
      action reports in terms of nursing practice and the utility of using after-action
      reports in a feedback loop to improve nursing training. This was a three-phase,
      mixed-method, qualitative study, using focus groups, phone surveys, and e-mail
      surveys to collect data. The sample consisted of 72 military nurses (Air Force,
      Navy, and Army) deployed in the last 4 years. The process of after-action
      reporting is unknown to the majority of nurse corps officers. Topics of concern
      in after-actions reporting included supplies, psychosocial issues, personnel,
      communications, logistics, and after-actions reporting process. Traditional
      written after-actions reporting has not provided an adequate feedback loop.
      Alternative methods suggested included "hot wash" meetings, online submissions, e
      mail contributions, and verbal debriefings. After-actions reporting could yield
      an excellent wealth of information, if reported in a timely and detailed manner,
      for nursing leaders.

PMID- 18333501
TI  - Successful treatment of disabling cholinergic urticaria.
AB  - A 22-year-old African American U.S. sailor presented with an intermittent
      pruritic eruption precipitated by mild activity for the last 2 years. She
      developed an extremely pruritic papular rash that would quickly coalesce into
      larger wheals following any exercise, light activity such as vacuuming, or taking
      hot showers. This condition had been getting progressively worse, preventing her
      from successfully completing her physical readiness test and other required
      physical training for the last 2 years. Previous treatment with antihistamines
      and steroids had failed to control her symptoms. She was diagnosed with
      cholinergic urticaria, successfully controlled with a combination of cetirizine,
      montelukast, and propanolol. She has since been returned to full military duty
      and is able to exercise regularly.

PMID- 18333502
TI  - Radiology corner. Answer to last month's radiology case and image:
      chondroblastoma with secondary aneurysmal bone cyst.

PMID- 18333503
TI  - Identification and detection of Macrophomina phaseolina by using species-specific
      oligonucleotide primers and probe.

PMID- 18333504
TI  - Association of ergot alkaloids with conidiation in Aspergillus fumigatus.
AB  - Ergot alkaloids are mycotoxins that affect the nervous and reproductive systems
      of exposed individuals through interactions with monoamine receptors. They have
      been studied more widely in ergot fungi and grass endophytes but also are found
      in Aspergillus fumigatus, an opportunistic human pathogen that reproduces and
      disseminates exclusively through conidia. The ergot alkaloids festucla-vine and
      fumigaclavines A, B and C are present in or on conidia of A. fumigatus. Cultures
      of the fungus that are free of conidia are difficult to obtain, obscuring
      comparisons of conidia versus vegetative hyphae as sources of the ergot
      alkaloids. To create conidiation-deficient strains of A. fumigatus we manipulated
      the bristle A gene (brlA), which controls vesicle formation or budding growth
      necessary for conidiation in Aspergillus spp. Disruption of brlA in A. fumigatus,
      via homologous recombination, resulted in a nonconidiating mutant that produced
      bristle-like structures instead of conidiophores and conidia. Moreover the
      disrupted strain failed to produce ergot alkaloids as verified by HPLC analyses.
      Complementation with a wild-type allele restored conidiation and ergot alkaloid
      production. These results suggest that ergot alkaloids are not produced within
      the vegetative mycelium of the fungus and are associated directly with
      conidiation.

PMID- 18333505
TI  - Significant diversity and potential problems associated with inferring population
      structure within the Cenococcum geophilum species complex.
AB  - Cenococcum geophilum is perhaps the most widely distributed and most recognized
      ectomycorrhizal fungus with a host range of more than 200 tree species from 40
      genera of both angiosperms and gymnosperms. We conducted a phylogenetic analysis
      on a large collection of isolates (n=74) from North America and Europe based on
      glyceraldehyde 3-phosphate dehydrogenase (gpd). A subset of isolates (n=22) also
      was analyzed with the more conservative LSU-rDNA locus. Significant nucleotide
      diversity was detected (approximately 20%) in the gpd region and the LSU-rDNA
      analysis supported that the C. geophilum isolates studied were monophyletic but
      distinct from two isolates, Am5-1 and N2-10, which previously were used in
      population genetic studies of this species. These results suggest that Am5-1 and
      N2-10 are likely two undescribed species or even genera. Our results suggest that
      C. geophilum sensu lato is a species complex and support previous molecular,
      physiological and morphological studies that have shown significant diversity in
      C. geophilum. This study also revealed that caution is advised when conducting
      population genetic studies in C. geophilum due to the possibility of pooling
      unrelated isolates. This potential problem also has implications for other fungal
      taxa because cryptic species routinely have been found in recent years based on
      molecular data.

PMID- 18333506
TI  - Worldwide phylogeny of Lactarius section Deliciosi inferred from ITS and
      glyceraldehyde-3-phosphate dehydrogenase gene sequences.
AB  - A phylogenetic analysis of Lactarius sect. Deliciosi was performed based on
      collections of all known species. Several samples of each species were included,
      originating from a wide geographic range. The two DNA regions we used (ITS and a
      part of the gene encoding glyceraldehyde-3-phosphate dehydrogenase) showed an
      incongruent phylogenetic signal. Much attention was paid to carefully observed
      macro- and micromorphological characters to draw taxonomic conclusions. We
      currently accept 38 taxa (31 species and seven varieties) in Lactarius sect.
      Deliciosi worldwide; four species are new to science. More sampling is needed to
      resolve the status of the North American varieties. Our knowledge of the Asian
      species in this section remains fragmentary. The monophyly of the section and its
      position within Lactarius subgenus Piperites, as proposed in recent morphology
      based classification schemes, is confirmed. The intrasectional relationships
      however do not coincide with the color of the latex (as previously supposed).
      Intercontinental conspecificity is low in general. The name L. deliciosus is
      wrongfully applied in North and Central America and only two species seem to
      occur in both Asia and Europe.

PMID- 18333507
TI  - Fomitopsis incarnatus sp. nov. based on generic evaluation of Fomitopsis and
      Rhodofomes.
AB  - A new polypore in the genus Fomitopsis was discovered in Kangwon Province, Korea.
      The species was morphologically similar to Fomitopsis rosea and F. cajanderi, but
      the pinkish white pore surface, the size and shape of the pores and the number of
      sterigmata were different enough for it to be distinguished from the recorded
      species of Fomitopsis. Based on the results of morphological and phylogenetic
      analyses, this new polypore is proposed as Fomitopsis incarnatus sp. nov.

PMID- 18333508
TI  - Five novel Candida species in insect-associated yeast clades isolated from
      Neuroptera and other insects.
AB  - Ascomycete yeasts are found commonly in the guts of basidioma-feeding beetles but
      little is known about their occurrence in the gut of other insects. In this study
      we isolated 95 yeasts from the gut of adult insects in five neuropteran families
      (Neuroptera: Corydalidae, Chrysopidae, Ascalaphidae, Mantispidae and
      Hemerobiidae) and a roach (Blattodea: Blattidae). Based on DNA sequence
      comparisons and other taxonomic characteristics, they were identified as more
      than 15 species of Saccharomycetes as well as occasional Cryptococcus-like
      basidiomycete yeasts. Yeast species such as Lachancea fermentati, Lachancea
      thermotolerans and Hanseniaspora vineae were isolated repeatedly from the gut of
      three species of corydalids, suggesting a close association of these species and
      their insect hosts. Among the yeasts isolated in this study 12 were identified as
      five novel Candida species that occurred in three phylogenetically distinct
      clades. Molecular phylogenetic analyses showed that Candida chauliodes sp. nov.
      (NRRL Y-27909T) and Candida corydali sp. nov. (NRRL Y-27910T) were sister taxa in
      the Candida albicans/ Lodderomyces elongisporus clade. Candida dosseyi sp. nov.
      (NRRL Y-27950T) and Candida blattae sp. nov. (NRRL Y-27698T) were sister taxa in
      the Candida intermedia clade. Candida ascalaphidarum sp. nov. (NRRL Y-27908T)
      fell on a basal branch in a clade containing Candida membranifaciens and many
      other insect-associated species. Descriptions of these novel yeast species are
      provided as well as discussion of their ecology in relation to their insect
      hosts.

PMID- 18333509
TI  - Transmission of the M2 double-stranded RNA in Rhizoctonia solani anastomosis
      group 3 (AG-3).
AB  - Horizontal transmission of the 3.57 kb M2 double-stranded RNA (dsRNA) between
      mycelia of somatically incompatible isolates of Rhizoctonia solani anastomosis
      group 3 (AG-3), an economically important pathogen of cultivated plants in the
      family Solanaceae, was investigated. Nine donor isolates of R. solani AG-3
      containing the M2 dsRNA were paired on potato-dextrose agar with each of three
      different recipient isolates where the M2 dsRNA was absent. Reverse-transcription
      PCR (RT-PCR) was used to detect horizontal transmission of the M2 dsRNA via
      hyphal anastomosis from donor to recipient isolates by examining hyphal explants
      taken 3 cm from the hyphal interaction zone. PCR-RFLP genetic-based markers of
      two nuclear loci and one mitochondrial locus were used to confirm identity and
      transmission between donor and recipient isolates of R. solani AG-3. The
      frequency of transmission observed between 72 pairings of the eight donor and
      three recipient isolates was approximately 4% of the total pairings, and
      differences in the phenotype of the recipient isolates after acquisition of the
      M2 dsRNA via horizontal transmission were observed. To our knowledge this
      represents the first demonstration of transmission of dsRNA between genetically
      different individuals of R. solani confirmed with nuclear and mitochondrial
      markers. These results suggest that transmission can occur between somatically
      incompatible isolates of R. solani AG-3 but that maintenance of the dsRNA in the
      recipient isolates was not stable after repeated subculturing on nutrient medium.

PMID- 18333510
TI  - Electrophoretic and cytological karyotyping of the foliar wheat pathogen
      Mycosphaerella graminicola reveals many chromosomes with a large size range.
AB  - The karyotypes of three isolates of Mycosphaerella graminicola, the septoria
      tritici blotch pathogen of wheat, were analyzed with both pulsed field gel
      electrophoresis (PFGE) and the cytological technique called germ tube burst
      method (GTBM). These analyses revealed a chromosome length polymorphism among
      these isolates. The estimated genome size was 31-40 Mb depending on the isolates,
      indicating 17-22% redundancy in the genome of the standard strain IP0323 because
      such differences do not affect development, pathogenicity and sexual reproduction
      of the other isolates. The chromosome numbers in the three isolates were 18-20
      and the chromosome size was 0.3-6 Mb. These data show that M. graminicola has the
      highest chromosome number and the smallest autosomes (A chromosomes) in
      filamentous ascomycetes. Our data also confirmed a large (> or =6 Mb) chromosome
      that was assembled recently in the IPO323 genome sequence. GTBM analyses revealed
      the mitotic metaphase chromosomes, enabling chromosome quantification, which was
      fully congruent with the PFGE analyses. These data will be instrumental in the
      final assembly of the M. graminicola genome.

PMID- 18333511
TI  - Genetic variability of Phytophthora sojae isolates from Argentina.
AB  - Phytophthora sojae causes root and stem rot, one of the most important diseases
      of soybean worldwide. Genetic diversity of 32 Phytophthora sojae isolates of
      different geographic origin from Argentina was evaluated with RAPD markers. The
      isolates were collected from diseased soybean plants and soil samples from Santa
      Fe, Buenos Aires, C6rdoba and Entre Rios provinces, in the Pampeana Region. DNA
      was amplified with 20 decanucleotides primers. Seven primers amplified 49
      fragments, of which 35 were polymorphic, indicating high variability. RAPD
      analysis detected intraspecific variability even among isolates of the same
      geographic origin.

PMID- 18333512
TI  - Tubeufia asiana, the teleomorph of Aquaphila albicans in the tubeufiaceae,
      pleosporales, based on cultural and molecular data.
AB  - The teleomorph of Aquaphila albicans was discovered on submerged wood collected
      in Thailand. Its black, soft-textured, setose ascomata, bitunicate asci and
      hyaline to pale brown, multiseptate ascospores indicated an affinity to
      Tubeufiaceae (Dothideomycetes). After morphological or molecular comparisons with
      related species in Tubeufia, Acanthostigma and Taphrophila, it is described and
      illustrated as a new species, T. asiana Sivichai & K.M. Tsui, sp. nov. Finding
      this Tubeufia teleomorph was surprising, given the falcate conidia of its A.
      albicans anamorph, which superficially resemble the conidia of Fusarium and not
      the coiled, helicosporous conidia of other species in Tubeufiaceae. We assessed
      the phylogenetic relationships of A. albicans-T. asiana with ribosomal sequences
      from SSU and ITS and partial LSU regions by parsimony and Bayesian analysis. An
      initial set of 40 taxa representing a wide range of ascomycete families and their
      SSU sequences from GenBank showed A. albicans-T. asiana to be nested within the
      Tubeufiaceae with 100% bootstrap support. Their placement was inferred with ITS
      and partial LSU ribosomal sequences. The nearly identical ITS sequences of two
      isolates of A. albicans and one isolate of Tubeufia asiana united these fungi as
      a monophyletic group with 100% bootstrap support and further nested them, with
      88% bootstrap support, in a clade containing Helicoon gigantisporum and Helicoma
      chlamydosporum. This is the first molecular phylogenetic study to place a
      nonhelicosporous species within the Tubeufiaceae and to show that helical conidia
      were lost at least once within the family.

PMID- 18333513
TI  - New neotyphodium endophyte species from the grass tribes stipeae and meliceae.
AB  - Several species of Achnatherum (grass tribe Stipeae) and Melica (tribe Meliceae)
      typically are infected by nonpathogenic, seed-transmissible fungi with
      characteristics of Neotyphodium species (anamorphic Clavicipitaceae). Molecular
      phylogenetic studies clearly have distinguished the endophytes from Achnatherum
      inebrians (from Xinjiang Province, China), A. robustum and A. eminens (both from
      North America) and indicate that the A. inebrians endophyte comprises a unique
      nonhybrid lineage within the Epichloe and Neotyphodium phylogeny, whereas the
      endophytes of A. robustum, and A. eminens are hybrids with multiple EpichlooY
      species (holomorphic Clavicipitaceae) as ancestors. Likewise distinct hybrid
      origins are indicated for Neotyphodium species from the European Melica species,
      M. ciliata and M. transsilvanica, the South African species M. decumbens and M.
      racemosa, and the South American species M. stuckertii. Neotyphodium species have
      been described from A. inebrians from Gansu Province, China, (N. gansuense), A.
      eminens (N. chisosum), M. stuckertii (N. tembladerae) and the South African
      Melica species (N. melicicola). However the endophytes from A. robustum and the
      European Melica species have not been described and the phylogenetic
      relationships of N. gansuense have not been investigated. Here we report a
      comprehensive study of morphological features and phylogenetic analyses of beta 
      tubulin and actin gene sequences on an expanded collection of endophytes from the
      Stipeae and Meliceae. These data provide a firm foundation for the description of
      two new Neotyphodium species, N. guerinii from M. ciliata and M. transsilvanica,
      and N. funkii from A. robustum. We also propose the new variety, N. gansuense
      var. inebrians for endophytes of A. inebrians from Xinjiang Province, which are
      morphologically and phylogenetically distinct from, yet clearly related to, N.
      gansuense from Gansu Province.

PMID- 18333514
TI  - Lectotypification of Agaricus brunnescens.
AB  - Agaricus brunnescens Peck sometimes is synonymized with A. bisporus (J. E. Lange)
      Imbach, the cultivated button mushroom. However this relationship has not been
      accepted universally or unreservedly. For various reasons A. bisporus is the more
      commonly used name. This study demonstrated that A. brunnescens is based on a
      heterogeneous type, as suggested by elements of the type description,
      correspondence at NYS and a lack of consensus among studies of the type. DNA
      sequence analysis indicated that material corresponding to both A. bisporus and
      A. subrufescens Peck is present in the type as presently constituted. A lectotype
      corresponding to the concept of A. bisporus is chosen, and nomenclatural issues
      are discussed. A definitive history of A. brunnescens is attempted.

PMID- 18333515
TI  - New species of the diaporthales from eastern Asia and eastern North America.
AB  - Seven previously undescribed diaporthalean species were found in eastern Asia and
      eastern North America. Three of these new species and one previously known
      species are assigned to a new genus Leucodiaporthe. Descriptions and
      illustrations are provided for the new taxa including Allantoporthe leucoth6es
      sp. nov., Diaporthella corylina sp. nov., Leucodiaporthe acerina sp. nov., L.
      juglandis sp. nov., L. maackii comb. nov., L. robiniae sp. nov., Leucostoma
      pseudoniveum sp. nov., Leucostoma excipienda comb. nov., and Phragmodiaporthe
      padi sp. nov.

PMID- 18333516
TI  - Type study of Mycena phaeophylla reveals its conspecificity with M. clavata.
AB  - An extensive taxonomic study based on the type collection of Mycena phaeophylla
      revealed its conspecificity with M. clavata. Redescription of Kuhner's original
      collections of M. phaeophylla is provided as well as a detailed description of M.
      clavata based on European material. A lectotype for M. phaeophylla is designated.
      Additional study on collections of M. speirea confirmed that this closely related
      species can be separated easily from M. clavata. New key to subsection
      Omphaliariae of section Hiemales is proposed.

PMID- 18333517
TI  - Xylaria species associated with nests of Odontotermes formosanus in Taiwan.
AB  - Nine species of Xylaria were collected in Taiwan from nests of Odontotermes
      formosanus, the only known macrotermitine termite in Taiwan. These include six
      newly described species, X. acuminatilongissima, X. atrodivaricata, X.
      brunneovinosa, X. griseosepiacea, X. intraflava and X. ochraceostroma, and three
      previously known species, X. cirrata, X. escharoidea and X. nigripes. We obtained
      cultures and ITS sequences from the nine species found in Taiwan and describe
      anamorphs for eight of them. Before the current study teleomorph-anamorph
      connections in the Xylaria species associated with termite nests have been
      established unequivocally in X. escharoidea only. Xylaria angulosa, X. fimbriata,
      X. kedahae, X. micrura, X. radicans, X. reinkingii and X. tolosa also are
      considered and annotated because they were reported to grow on ground and likely
      are associated with termite nests. Epitypifications are made for X. cirrata, X.
      escharoidea and X. nigripes. Xylaria sanchezii is considered a nomen dubium.
      Photographs are presented for most of the aforementioned species. A dichotomous
      key to 25 Xylaria species growing on termite nests or ground also is given.

PMID- 18333518
TI  - The need for formal paediatric resuscitation training in Pakistan.

PMID- 18333519
TI  - Traumatic spinal cord injuries at a tertiary care rehabilitation institute in
      Pakistan.
AB  - OBJECTIVE: To identify the epidemiological pattern of traumatic spinal cord
      injuries (SCI) presenting at a rehabilitation institute of a developing country.
      METHODS: Eighty three patients of traumatic SCI admitted at Armed Forces
      Institute of Rehabilitation Medicine in 2006 fulfilling the inclusion criteria
      were enrolled. Detailed clinical evaluation and radiological assessment was done
      along with identification of mechanism of injury, mode of evacuation and presence
      of associated injuries. Data analysis was done in January 2007 and results were
      compiled and analyzed using SPSS 13. RESULTS: There were 68 (81.9%) males and 15
      (18.1%) females. Mean age was 28.3 +/- 12.4 years. Majority of the patients were
      in their second decade 43 (51.8%) years. Ambulance evacuation was carried out in
      only 18 (22.2%) patients and none received any spinal trauma first aid and log
      roll at the injury site. Most of the patients were paraplegics 49 (71.1%), 48
      (57.8%) had complete injury and 43 (51.8%) spinal fixation. Fracture dislocation
      was the predominant vertebral column injury in 25 patients. Associated injuries
      and problems were present in 49.4% patients. CONCLUSION: Epidemiology of SCI in a
      developing country has unique epidemiological features and problems, which is
      different from a developed country. This was to be considered while formulating a
      plan for SCI management and rehabilitation. There is a dire need to establish a
      SCI registry in Pakistan, in order to improve the spinal trauma evacuation
      protocols and develop spinal rehabilitation centers.

PMID- 18333520
TI  - Knowledge, attitudes and practices of health care workers regarding needle stick
      injuries at a tertiary care hospital in Pakistan.
AB  - OBJECTIVE: To assess the knowledge, attitude and practices of HCWs regarding
      needle stick injuries at the Aga Khan University Hospital. METHODS: A cross
      sectional study was conducted on medical personnel. A structured pre-tested
      questionnaire was administered during June-July 2003. The data was analysed by
      SPSS 13.0. Percentages of the categorical variables were computed and compared by
      Chi square test at a 5% level of significance. Odds ratios and their 95% CIs were
      also computed. RESULTS: Of 80 participants, 29 were doctors and 51 were
      registered nurses. About 45% reported having a needle stick injury in the past.
      Frequency of injury was significantly higher among doctors (p < 0.001). The most
      common reason identified was stress or being over burdened followed by careless
      attitude. More than 50% of the injuries occurred while injecting or drawing blood
      samples. The risk of getting infections was well known amongst both the groups.
      Two third of participants were familiar with the prevention protocols and
      practices of nurses were generally safer than doctors (p < 0.001). CONCLUSION:
      Despite knowing the risks, frequency of needle stick injury was generally higher
      especially among doctors reflecting bad practice and careless attitude towards
      work. Mandatory reporting, proper follow-up and constant reinforcement are
      recommended to reduce the rate of nosocomial transmission to health care workers.

PMID- 18333521
TI  - Acute renal failure in pregnancy: one year observational study at Liaquat
      University Hospital, Hyderabad.
AB  - OBJECTIVE: To determine the incidence of pregnancy related acute renal failure
      (ARF), clinical spectrum, morbidity and mortality of this preventable
      complication of pregnancy. METHODS: An observational and prospective hospital
      based study was conducted at a tertiary care hospital in Hyderabad for one year
      from Nov. 2004-Oct. 2005. Total 116 patients of ARF were admitted in Nephro
      Urology ward during this period of whom 42 were of obstetric related ARF and they
      were included in the study. A pre-designed proforma was used. The clinical
      history was noted and all underwent a physical examination. Urine output was
      recorded. Routine laboratory tests were performed and specialized tests as DTPA
      scan was done in some cases. The final outcome was recorded. The majority i.e. 31
      patients were from village community of interior Sindh province and the remaining
      11 were from Hyderabad city area. RESULTS: Pregnancy related ARF numbered 42
      (36%) of which 28 (67%) were multipara and 14 (33%) were primigravida. Their ages
      were between 20 to 41 years. Majority 24 (57%) patients had not received any
      antenatal care and there was a history of traditional birth attendants TBA (Dai)
      assisted home delivery as compared to 6 (14%) cases with adequate antennal care.
      Six (14%) cases presented in their first trimester of pregnancy while 36 (86%)
      patients developed ARF in their 3rd. trimester or in the puerperium and 19 (45%)
      were anuric. Blood loss causing hypotension due to APH and PPH was the common
      cause of ARF. Clinical spectrum of pregnancy related ARF showed APH in 6 (14%)
      cases, PPH in 9 (24%) cases, septic abortion and puerperal sepsis and DIC in 13
      (31%) cases, IUD in 6 (14%) and preeclampsia / eclampsia in 5 (12%) cases. Thirty
      (71%) patients received haemodialysis and 12 (29%) did not require dialysis.
      Commonest clinical diagnosis was ATN in 23 (55%) cases with complete recovery.
      Acute bilateral renal cortical necrosis was seen in 9 (21%) cases and 2 (5%)
      patients had patchy cortical necrosis. Overall morbidity was 19% and mortality
      26%. CONCLUSION: Pregnancy related acute renal failure is a major health, problem
      especially in the villages of Sindh provinces and carries very high mortality and
      morbidity. Poor healthcare facilities and lack of antenatal healthcare clinics
      are major identified causes.

PMID- 18333522
TI  - Is Expanded Programme on Immunization doing enough? Viewpoint of health workers
      and managers in Sindh, Pakistan.
AB  - OBJECTIVE: To understand health managers' and service providers' views about
      routine immunization; perceived barriers and practical measures to improve the
      situation in three districts of rural Sindh and one town of Karachi, Pakistan.
      METHODOLOGY: Key informants interviews and focused group discussions were carried
      out involving district and town health officers, health providers, vaccinators,
      lady health visitors and lady health workers. RESULTS: The study result showed
      that the problems hampering the routine immunization related mainly to lack of
      incentives and restricted mobility of health workers in the field. Political
      interference, flaws in monitoring of routine immunization, disinterest of
      facility based doctors and lack of private sector involvement in the provision of
      vaccine are other major problems. National immunization days (NIDs) so far had a
      negative impact on routine immunization coverage. CONCLUSION: There is need of
      policy shift to integrate routine immunization with NIDs for polio which will
      help in improving routine immunization along with eradication of Polio. More
      incentives and clear service structure for vaccinators will raise the motivation
      among the EPI staff. The budgetary constraints must be overcome by involving all
      stakeholders both foreign and local. Public and private sector must work hand in
      hand to achieve the goal. Lastly, political will and support is mandatory to
      sustain the efforts of EPI.

PMID- 18333523
TI  - Role of tryptophan in the pathogenesis of hepatic encephalopathy.
AB  - OBJECTIVE: To monitor serum levels of total and free tyryptophan in various
      hepatic dysregulations. METHOD: The study was conducted on 36 adult patients. All
      were suffering from acute or chronic liver diseases such as hepatitis (n = 12),
      cirrhosis (n = 12) and Hepatic Encephalopathy (HE) (n = 12). Patients of all age
      groups and both genders were included. Serum levels of Tyryptophan (TRP) were
      measured by HPLC-EC. Albumin and bilirubin were analyzed by kit method (Merck).
      RESULTS: The serum levels of total TRP (p < 0.01) was found in all patients. Free
      TRP significantly (p < 0.01) increased only in HE. Patients with hepatitis and
      cirrhosis did not show significant change in serum free TRP. The Albumin levels
      significantly decreased in hepatitis, cirrhosis and in HE (p < 0.01). All
      patients exhibited hypoalbuminaemia (p < 0.01). CONCLUSIONS: The results suggest
      that an increased ratio of free to bound TRP enhances its availability to the
      brain, which in turn increases 5-HT synthesis thus precipitating encephalopathy.

PMID- 18333524
TI  - Sperm swim-up: a simple and effective technique of semen processing for
      intrauterine insemination.
AB  - OBJECTIVE: To study the impact of sperm swim up technique of seminal processing
      for the purpose of intrauterine insemination (IUI) in couples presenting with
      subfertility. METHODS: Hundred and twenty-one couples presenting with
      subfertility underwent 281 cycles of IUI in Combined Military Hospital Kharian,
      Lahore and PNS SHIFA Karachi from June 2002 to March 2005. Men had prior semen
      analysis to assess for parameters like those that total sperm count, morphology
      and progressive motility. Only those couples were enrolled in whom there was
      either no obvious cause or the male partner had some problem with the seminal
      counts/motility. In standard swim-up technique, after liquefaction, the semen
      sample was centrifuged and supernatant was discarded. Pellet was suspended in pre
      warmed 2.5 ml of Ham's F-10 culture medium and thereafter centrifuged once more.
      The pellet was gently over-layered with medium in the tube which was sealed,
      inclined at 45 degrees and kept at 37 degrees C for 60-90 minutes in 5% CO2. A
      sterile Pasteur pipette was used to remove the supernatant containing actively
      motile sperms. The specimen was kept at 37 degrees C till dispatched to be
      inseminated. Data was analyzed by using SPSS version-10. Motility and morphology
      were used to present qualitative parameters and chi-square test was applied to
      assess the effectiveness of IUI in relation with these variables. RESULTS: Post
      swim-up semen parameters including total motile sperm count and motility were
      observed. There was a trend towards an increased sperm count, motility and
      pregnancy rate after the swim up procedure. CONCLUSION: Our findings suggest that
      sperm swim-up technique is an easy reliable and effective sperm processing method
      for insemination purposes.

PMID- 18333525
TI  - Socio-demographic correlates of exhaled breath carbon monoxide in Karachi's adult
      population.
AB  - OBJECTIVE: To examine the relationship between CO levels and putative factors
      including smoking status among residents of Karachi, an urban center with very
      high levels of air pollution. METHODS: Two hundred and eighteen volunteering
      subjects were asked to maximally exhale into a Smokerlyzer breath CO analyzer.
      Each of the volunteers was also asked to reply to a questionnaire-based interview
      seeking demographic information as well as details of exposure to tobacco,
      traffic fumes and other air pollutants. RESULTS: Out of the 218 participating
      subjects, 75% were males and 27% were current or ex-smokers. The mean CO level
      was 2.92 parts per million (ppm). Cigarette smoking was the only factor found to
      influence CO levels. Number of cigarettes smoked per day was directly related to
      CO levels, while time since the last smoke was inversely related. There was no
      difference in CO levels between ex-smokers and never-been-smokers. Years of
      residence in Karachi, quantitative exposure to traffic and perception of
      occupational exposure to air pollutants were not associated with CO levels.
      CONCLUSIONS: Smoking status, number of cigarettes smoked per day and time since
      last smoke correlated well with exhaled breath CO levels, in spite of high air
      pollution levels. This tool therefore continues to provide a valid and real-time
      assessment of a subject's current smoking status.

PMID- 18333526
TI  - Role of exercise in osteoporosis prevention--current concepts.
AB  - Osteoporosis is a metabolic disorder of the bones due to loss of both bone
      mineral and bone matrix in equal proportions resulting in a bone that is weak and
      unable to support the body. This becomes a problem in the elderly who are then at
      risk of frequent fractures increasing the morbidity and mortality. Measures taken
      early in life in the form of calcium and exercise go far in preventing the
      development of this disorder. The primary purpose of this narrative review is to
      evaluate the current literature and to provide insight into the role of exercise
      relating to osteoporosis. Emphasis is given to the importance of the specific
      types of exercises needed to increase bone strength and muscle power, keeping in
      view the age and general physical condition of the person.

PMID- 18333527
TI  - Informed consent and some of its problems in Pakistan.
AB  - Informed consent has become an essential element of human subject research.
      Certain components are essential for a well-understood informed consent. There
      are problems in procurement of a comprehensive and meaningful consent in the
      Pakistani research settings. The inefficient healthcare systems, low literacy
      rate with masses having no concept of individual rights, higher social status
      enjoyed by physicians inhibiting the patients from questioning them, and
      unwillingness to hear bad news are some of these factors. Establishing Bioethics
      education at all levels, encouraging the involvement of families in decision
      making, using improvisation in procurement of consent are suggested solutions.
      There needs to be a consideration for both beneficence and autonomy with emphasis
      on balancing and doing equal justice to both.

PMID- 18333528
TI  - Sedation-analgesia in non operative locations: practice trends of anaesthetists.
AB  - Sedation/analgesia is a mode of anaesthesia which facilitates an uncomfortable or
      painful procedure, such as gastrointestinal endoscopy, in a rousable and
      cooperative patient. The objective of the study was to assess the practice trends
      for administering sedation analgesia in non operative locations in Aga Khan
      Hospital, Karachi by anaesthetists. It was a descriptive study which
      retrospective reviewed anaesthesia records. A total of 41 ASA I-IV cases were
      reviewed. Non invasive cardiorespiratory monitoring and clinical sedation
      monitoring were applied. Intravenous Propofol infusion and midazolam boluses were
      used, singly or in combination with fentanyl boluses. All our patients recovered
      uneventfully within 5 minutes of the end of procedure. The practice trends for
      drug regimens are similar to those reported in recent literature. However we need
      to provide BIS monitoring, target controlled and patient maintained sedation to
      enhance patient and operator comfort.

PMID- 18333529
TI  - Magnetic resonance imaging (MRI) findings in white matter disease of brain.
AB  - Demyelinating and dysmyelinating white matter diseases are important components
      of neurological problems. Recently, Magnetic Resonance Imaging (MRI) has played a
      key role in diagnoses of white matter diseases. Therefore, the purpose of the
      current study is to evaluate the usefulness of MRI in determining the type and
      frequency of white matter disease. We studied 35 patients who visited the
      Radiology Department of the Aga Khan University Hospital (AKUH) for MRI with
      suspected demyelinating/dysmyelinating disorder from January 2003 to December
      2005. Multiple Sclerosis (MS) (17; 48%) and leukodystrophies (10; 29%) were the
      most common diseases. The MRI helped identify the sites and types of the lesion
      precisely and thereby helped made clearer. distinction between various types of
      white matter diseases. The current study demonstrated the effective use of the
      imaging and clinical presentation for arriving at the correct diagnosis.

PMID- 18333530
TI  - An open study to assess the safety and efficacy of Heprovac-B vaccine 10 mcg-dose
      for adults.
AB  - Heprovac B is a novel recombinant vaccine. There are many vaccines available in
      Pakistani market but Heprovac B claims to be immunogenic even at 10 meg dose. Aim
      of the study is to determine whether using 10 meg of Heprovac B vaccine is safe
      and effective in producing sufficient immunity in Pakistani population. One
      hundred and twenty five subjects, who fulfilled the Inclusion criteria, were
      enrolled for the study. Heprovac B was administered in a three-dose regimen given
      at 0, 1 and 6 months and adverse events were recorded. Immunogenicity was tested
      by measuring hepatitis B surface antibody one month after each dose received. One
      month after the 3rd dose 98.7% of the subjects were found to be seroprotected
      with geometric mean titer of 488.83 mIU/1 after the third dose. Heprovac B,
      vaccine was well tolerated with minimal reported adverse events. It is safe and
      10 mcg is immunogenic in producing antibodies in Pakistani population against
      Hepatitis B virus.

PMID- 18333531
TI  - A fatal case of gram negative bacterial sepsis associated with disseminated
      strongyloidiasis in an immunocompromised patient.
AB  - We report a fatal case of disseminated strongyloidiasis in a patient with
      multiple myeloma receiving chemrotherapy. A fifty-seven years old man presented
      with severe diarrhoea and vomiting, fever, weight loss and dysphagia,due to mouth
      ulcers. Despite broad-spectrum intravenous antibiotics, albendazole (anti
      protozoal) and supportive treatment, the patient died of Gram-negative sepsis.

PMID- 18333532
TI  - Research qualifications in medicine: what is the importance?

PMID- 18333533
TI  - Byssinosis: as seen in cotton spinning mill workers of Karachi.
AB  - OBJECTIVE: To identify Byssinosis in cotton spinning mill workers, probable
      associations of disease with factors such as different work areas, safety gadget
      usage and overtime and to ascertain proportions of byssinosis to accidental
      injuries. METHODS: This study was conducted in a spinning mill of Karachi in June
      2006. Mill workers who had worked for a period of minimum 5 years were selected.
      A sample size of 83 conveniently selected workers participated in the research
      study. Data collection was done via questionnaire, and pulmonary function tests.
      RESULTS: The mean age of the sample was 30 +/- 6.9 years. Of all the workers 72%
      used safety gadgets (masks) while working and 50% availed overtime. Smokers
      amounted to 31% of the total subjects. Around 35% workers complained of having
      respiratory ailments of which 19% (16 workers) closely matched byssinotic
      symptoms. Pulmonary Function Tests (PFTs) confirmed 13 of 16 workers to be
      byssinotics, with the remaining being labeled as Probables. The overall
      proportion of Byssinotics in the mill was 19.28% (95% C.I. 11-27) and that of
      accidental injuries was 22.9%. The association of byssinosis with respect to work
      areas was significantly high in Ring area (O.R. = 2.04) followed by carding (O.R.
      = 1.3). The association of byssinosis was also high in workers who did not use
      safety gadgets, e.g. dust masks (O.R = 4.89) and in people who worked overtime
      (O.R. = 1.82). Associations with respect to duration of employment and smoking
      could not yield significant results. CONCLUSION: Results indicate a very high
      probability of association of disease to non-usage of safety gadgets and overtime
      working. Studies comprising of a greater sample size would show precisely the
      overall prevalence of the disease.

PMID- 18333534
TI  - Being active against passive smoking.

PMID- 18333535
TI  - [Apparent life-threatening event (ALTE) in young children: the importance of
      recognition of the symptoms].
AB  - An Apparent life-threatening event (ALTE) mostly occurs in infants under 6 months
      of age and can generate considerable anxiety in the parents. In most cases, by
      the time the child presents in general practice, the general practitioner sees a
      healthy looking infant and all symptoms have disappeared. There is some
      discrepancy between the healthy looking child and the alarming history of the
      event, with an unresponsive, pale or cyanotic, and apparently not breathing
      child. The general practitioner must take a careful history and perform a
      thorough physical examination to determine the possible cause of the event and to
      decide whether clinical observation is necessary. In this article, two cases are
      presented in which an infant presented to a general practitioner with an ALTE.
      Clinical observation is indicated in almost all cases of an ALTE, and in 50% of
      the cases a cause for the event is found. The purpose of the present report is to
      give the general practitioner information on the practical aspects of the
      management of infants that have experienced an apparent life-threatening event.

PMID- 18333536
TI  - ['Drops for allergy' in children: often applied, but not effective].
AB  - The practice of using an 'allergy service', supported by manufacturers of
      sublingual immunotherapy, should be discouraged for a number of reasons. There is
      an obvious conflict of interest when an employee from a commercial firm with an
      interest in allergy treatment is involved in interpreting allergy tests and
      discussing treatment. Most allergic diseases can be well controlled with drug
      therapy, without having to resort to immunotherapy. Finally, no good evidence
      exists to prove clinically relevant effects of sublingual immunotherapy in
      children with atopic disease. Until results of well-designed studies become
      available, sublingual immunotherapy in children should not be used.

PMID- 18333537
TI  - [Obscurity still exists with regard to the policy in undescended testes: early
      operation versus well-underpinned wait-and-see policy].
AB  - The frequency of orchidopexy in the Netherlands is higher than the frequency of
      genuine undescended testes in spite of an existing consensus guideline on the
      subject. Evidence that orchidopexy has a positive effect on fertility or the
      decrease of testicular malignancy is lacking. Clinical trials are necessary to
      answer the question whether orchidopexy before the age of 2 years prevents
      malignancy or improves fertility. It is important that research that shows no
      results of early orchidopexy is also published. A public health approach is
      necessary to prevent unnecessary surgical interventions.

PMID- 18333538
TI  - [Undescended testis: current views and advice for treatment].
AB  - --Undescended testis (UDT) is one of the most common urogenital abnormalities in
      boys. --UDT is defined as a testis which cannot be brought into a stable scrotal
      position. --At present, congenital and acquired forms of UDT are recognised.
      Congenital UDT is defined as a UDT which has never descended from birth. Acquired
      UDT is defined as a UDT which has been fully descended in the past. --Congenital
      UDT should be treated surgically between 6 to 12 months of age. --The treatment
      of acquired UDT is still disputed. As yet, awaiting spontaneous descent at early
      puberty seems to be the most rational treatment. --In the Netherlands, the high
      number of late orchidopexies is due to surgery for acquired UDT. To reduce this
      high number, the guidelines of the first development conference on 'non-scrotal
      testis' dating back to 1986 should be revised on several points.

PMID- 18333539
TI  - [The undescended testis: arguments in favour of early treatment, provided
      retractile testis and acquired non-scrotal testis have been excluded].
AB  - --Guidelines for the treatment ofundescended testis (UDT) are sparse. Often an
      operation in the second year of life is advised. --Recent data indicate that the
      normal maturation process, which will ultimately lead to a normal quantity and
      quality of germ cells, is impaired as early as in the first half year of a
      newborn's life. None of the guidelines take this into account. Spontaneous
      descent after the fourth month following birth, of testes that have previously
      not descended, hardly ever occurs. --No differences have been shown in
      complication numbers between surgery before and after the first birthday.
      Orchidopexy prior to the 13th birthday reduces the risk of testicular cancer. -
      Therefore, based on these data, it is advised to perform orchidopexy in the
      second half of the first year of a newborn's life. In older boys a UDT must be
      treated before the 13th birthday. --In the Netherlands a lot more orchidopexies
      are done despite what may be expected based on prevalence numbers of UDT: testes
      retaining a normal volume that would most probably have descended spontaneously
      come puberty. --It remains important to carry out a careful physical examination
      and document the position of the testes soon after birth, and later on if UDT is
      suspected, to avoid unnecessary operations on retractile testes and acquired UDT.

PMID- 18333540
TI  - [Diagnostic image (359). A 13-year-old girl with intermittent claudication].
AB  - A 13-year-old girl suffered from intermittent claudication in the right calf
      caused by a type III popliteal artery entrapment syndrome due to an accessory
      muscle bundle of the medial gastrocnemius head.

PMID- 18333541
TI  - [Sublingual immunotherapy in children with asthma or rhinoconjunctivitis: not
      enough evidence because of poor quality of the studies; a systematic review of
      literature].
AB  - OBJECTIVE: To determine the evidence of the efficacy and safety of sublingual
      immunotherapy (SLIT) as a curative therapy for allergies in children. DESIGN:
      Systematic review. METHOD: All randomised, double blind and placebo-controlled
      studies (DBRPCT's) on SLIT in asthma or rhinoconjunctivitis in children were
      selected from Medline, Embase and Cochrane Central Register of Controlled Trials.
      Also references of the found articles were used. The selected studies were
      assessed for quality and the different outcomes were evaluated. RESULTS: 13
      DBRPCT's on SLIT in children were selected, 5 studies on children with house dust
      mite allergy and 8 studies on children with grass pollen allergy. There was
      considerable heterogeneity among the different studies with respect to the choice
      and definition of outcome criteria. The quality of the included studies was
      moderate. After treatment with SLIT, especially reported symptoms decreased
      without improvement of objective parameters. Positive results originated
      especially from significant differences within the intervention group before and
      after treatment. CONCLUSION: It was not possible to substantiate the claim of
      authors of the studies regarding the favourable effects of SLIT in children with
      asthma or rhinoconjunctivitis, since all studies had serious methodological
      flaws. However, the studies showed that SLIT seems to be safe in children in the
      doses applied.

PMID- 18333542
TI  - [An early switch from intravenous to oral antibiotics is equally effective as the
      standard intravenous therapy in severe community acquired pneumonia].
AB  - OBJECTIVE: To compare an early switch from intravenous to oral antibiotics with
      the standard intravenous therapy in patients admitted to hospital with severe
      community acquired pneumonia. DESIGN: Multicentre randomised prospective trial
      with follow-up at 28 days. METHOD: Patients with severe pneumonia who were
      admitted to hospital were randomised for 7 days intravenous antibiotic therapy
      (control group) or for an early switch to oral antibiotic therapy after 3 days of
      intravenous antibiotic therapy (intervention group). An intention-to-treat
      analysis was performed. The primary outcome measure was clinical cure. The length
      of hospital stay was a secondary outcome measure. RESULTS: Out of the 302
      patients included in the trial, data was analysed from 265 patients. The
      mortality rate in the intervention group did not differ significantly from that
      of the control group (mean difference: 2%; 95% CI: -3-8). After 28 days, 83% of
      the patients in the intervention group and 85% in the control group were
      clinically cured (mean difference: 2%; 95% CI: -7-10). The length of hospital
      stay was 1.9 days shorter in the intervention group (95% CI: 0.6-3.2 days).
      CONCLUSION: An early switch from intravenous to oral antibiotics in patients
      admitted to hospital for severe community acquired pneumonia is safe and reduces
      the length of hospital stay by approximately 2 days.

PMID- 18333543
TI  - [A boy with cyclic vomiting and an alleged furosemide allergy on the basis of a
      subpelvic stenosis].
AB  - An 8-year-old boy, known with a Diamond-Blackfan anaemia, was admitted to the
      hospital because of frequent vomiting since 3 days and loin pain. In previous
      years, he had been admitted several times for the same complaints but no cause
      had been identified. Ultrasound examination of the abdomen performed at
      admittance showed dilatation of the left renal pelvis. A renal scintigraphy was
      discussed with the mother, and she refused the injection of furosemide, because
      her son was allegedly allergic to furosemide: previous furosemide treatments
      during blood transfusions for his anaemia had always resulted in stomach-ache and
      vomiting, which may be attributed, however, to an acute dilatation of the renal
      pelvis due to the diuretic effect of furosemide. Scintigraphy without furosemide
      showed a significant obstruction and asymmetric renal function, so a pyeloplasty
      was performed after which he has been symptom-free. In patients with cyclic
      vomiting, an intermittent uretero-pelvic junction obstruction should be
      considered and can only be ruled out when ultrasound during the complaints and
      renal scintigraphy under adequate hydration and after furosemide are normal.

PMID- 18333544
TI  - [Metabolic encephalopathy can be a potentially life-threatening complication from
      valproic acid].
AB  - In two female patients of 62 and 81 years old, a metabolic encephalopathy was
      diagnosed which was ascribed to the use of valproic acid. Both had elevated
      ammonia levels in arterial blood, without hepatic failure. The first patient
      eventually became comatose and required artificial ventilation. After
      discontinuation of the valproic acid and with the aid of supportive measures,
      both women recovered. In patients with an impaired level of consciousness who are
      using valproic acid, a metabolic encephalopathy caused by this drug should be
      considered. Elevated levels of ammonia can be found but are not mandatory.
      Discontinuation of valproic acid will lead to recovery of consciousness.

PMID- 18333546
TI  - [Serious complications of umbilical venous catheterisation].

PMID- 18333547
TI  - [Invasive zygomycosis in patients treated for haematological malignancies].

PMID- 18333548
TI  - [Total atrioventricular block following a tick bite].

PMID- 18333549
TI  - [Granulomatous mastitis: a rare cause of breast swelling].

PMID- 18333550
TI  - Equality for gay staff can only be good for the workforce as a whole.

PMID- 18333551
TI  - Pride and prejudice.
AB  - Prejudice in health services towards lesbian, gay, bisexual and transgendered
      people still exists, even though much has changed since the 1950s.

PMID- 18333552
TI  - Crossing the pain barrier.
AB  - Nurses working in many settings should be alert to the possibility that a patient
      has been subjected to homophobic assault.

PMID- 18333553
TI  - Lifting the curse.
AB  - Adenomyosis is a condition most women have never heard of. Yet it can cause
      severe menstrual cramping and heavy bleeding.

PMID- 18333554
TI  - Bearing the cross.

PMID- 18333555
TI  - Delegation of medication administration: an exploratory study.
AB  - AIM: To examine the delegation of medication administration, including the
      frequency of delegation, whether delegation was to a care worker or a registered
      nurse (RN) and whether care workers were directly supervised when administering
      medication. METHOD: Administration of 1313 medication doses was observed on two
      inpatient psychiatric wards for older people. RESULTS: Administration was
      delegated by the nurse preparing the medication for four out of every five doses,
      usually to another registered nurse (78% of delegated doses), but also to care
      workers (22%). Care workers were more likely to administer medications to
      confused and aggressive patients than were registered nurses. CONCLUSION: Care
      workers who undertake delegated medication administration should receive regular
      training to ensure safety. Nurses remain accountable for delegated medication
      administration.

PMID- 18333556
TI  - Removal of short-term indwelling urethral catheters.
AB  - This information on best practice discusses the evidence for the removal of short
      term indwelling urethral catheters. The article has been reproduced with the
      permission of the Joanna Briggs Institute (JBI). The article is derived from a
      systematic review of research published by the JBI,'Comparison of late night and
      early morning removal of short-term urethral catheters: a systematic review'
      (Fernandez et ol 2003), and another published in the Cochrane Library 'Policies
      for the removal of short-term indwelling urethral catheters' (Griffiths and
      Fernandez 2005). The primary references on which this information is based are
      available in the systematic review reports to members of the JBI via the website:
      www.joannabriggs.edu.au and the Cochrane Library.

PMID- 18333557
TI  - Lumbar puncture.
AB  - This article discusses the need for lumbar puncture, preparation of the patient
      and equipment necessary for this procedure. The rationale for the intervention is
      described with a focus on the nursing management before, during and after the
      procedure.

PMID- 18333558
TI  - Multiple system atrophy: pathophysiology, treatment and nursing care.
AB  - This article gives a brief overview of the symptoms and management of multiple
      system atrophy, a degenerative neurological condition causing parkinsonism,
      ataxia and autonomic dysfunction. It focuses on the role of the nurse in the
      context of a multidisciplinary team because holistic care is essential to promote
      patient independence and maintain quality of life. Because the condition is
      progressively disabling and shortens life, nurses are ideally placed to support
      patients and their families, both physically and emotionally.

PMID- 18333559
TI  - Erectile dysfunction.

PMID- 18333560
TI  - Nursing the planet.

PMID- 18333561
TI  - Calm and collected.

PMID- 18333562
TI  - Confident to come out.

PMID- 18333563
TI  - GPs key in detecting psychosis.

PMID- 18333564
TI  - Early detection of erectile dysfunction may prevent CVD.

PMID- 18333565
TI  - When should patients with BPH be referred?

PMID- 18333566
TI  - Improving disease outcomes in men.

PMID- 18333567
TI  - The diagnosis of general paralysis. 1908.

PMID- 18333569
TI  - Serjeant-Surgeons, the Barber-Surgeons' Company and the Navy.

PMID- 18333570
TI  - Doing it by the book: what the libraries of the Royal Naval Hospitals can tell us
      about naval medicine in the nineteenth century.

PMID- 18333571
TI  - The truth about MTAS...

PMID- 18333572
TI  - An Evaluation of the Medical Training Application Service as experienced by
      Defence Medical Service Medical Officers.
AB  - OBJECTIVES: In 2007 Defence Medical Service (DMS) Medical Officers (MOs) applying
      to train within hospital based specialities were selected using the Medical
      Training Application Service (MTAS). Recognising the problems being reported
      about MTAS, the Defence Postgraduate Medical Deanery (DPMD) conducted an
      evaluation in order to assess whether DMS MOs had also experienced problems with
      the MTAS process. METHODS: DMS MO applicants were sent an email questionnaire,
      requesting both graded (Likert scale) and narrative responses, to gauge their
      opinion about the application service. The questionnaire covered the technical
      aspects of the process, the support available and the ability to demonstrate
      appropriate knowledge and skills. RESULTS: Only 42 responses (32%) were received.
      However, having considered areas of potential bias, the graded questionnaire
      results and thematic analysis of the narrative responses showed a clear consensus
      amongst the applicants in many areas. More than three quarters (78%) of DMS
      applicants criticised the opportunity to record their abilities and achievements,
      and 91% recorded that the questions were unable to differentiate between
      candidates. These views were mirrored in the narrative responses, with more than
      130 statements covering five topic areas highlighting areas for improvement.
      Strong support was recorded for the work and advice provided by DPMD in support
      of the candidates. CONCLUSIONS: DMS MOs presented very negative opinions of their
      experiences of MTAS, highlighting their perceptions that they were unable to
      record their particular skills and experiences and that the questions were unable
      to discriminate between specialties. Particular difficulties were reported in
      presenting non-NHS experiences and skills.

PMID- 18333573
TI  - The team works--a multidisciplinary challenge.

PMID- 18333574
TI  - How many of our patients are military? A study of Emergency Department attendance
      at Derriford Hospital, March to August 2006.

PMID- 18333575
TI  - Atrioventicular block in familial amyloidosis; revisiting an old debate.
AB  - Familial amyloidosis with polyneuropathy (FAP) is the rarest of the cardiac
      amyloidoses, with less than 200 cases diagnosed each year. In this disease,
      cardiac involvement is characterized by extracellular amyloid infiltration
      throughout the heart, usually resulting in sinoatrial nodal dysfunction,
      cardiomyopathy, and congestive heart failure. While cardiac conduction
      disturbances are a common feature of FAP, the mechanism of these disturbances
      seems to be a point of contention among researchers. We present a case of a 78
      year-old man with a history of FAP admitted with the diagnosis of atrial
      fibrillation/flutter. After failing to convert to normal sinus rhythm despite
      medical therapy, an electrical cardioversion was performed. Following the
      procedure, the patient converted to symptomatic Mobitz type two second-degree
      atrioventricular block and required dual chamber pacemaker placement. Our case
      emphasizes the potential consequences of cardioversion in this progressive
      condition and the need for further studies on the pathophysiology of cardiac
      involvement in FAP.

PMID- 18333576
TI  - Death certificates: a part of life.

PMID- 18333577
TI  - Pediatric hospitalist: a national and regional trend.
AB  - The pediatric hospitalists in South Carolina at all three academic centers have
      expanded their clinical role by acting as referral physicians during a patient's
      hospital stay for surgeons, subspecialists, and/or primary care providers. In
      addition they have taken on the challenge of improving quality of care by
      offering clinical services, such as palliative care and consults, and are serving
      as the leaders for hospital system focus on quality improvement including
      improved patient safety. Specific recognition of pediatric hospitalists and
      hospitalists in general as a subspecialty is moving forward. Recently, the
      American Board of Internal Medicine approved the creation of a certificate for
      hospitalists in internal medicine and there are numerous pediatric hospitalist
      fellowships. Nationally, multiple societies have formed for this growing group of
      new physicians including the American Academy of Pediatrics Section on Hospital
      Medicine, Society of Hospital Medicine Section for Pediatric Hospitalists, and
      the Ambulatory Pediatric Associations Section on Pediatric Hospitalists. While it
      may be thought that hospitalists are merely generalists that work in the hospital
      and therefore should not be considered a separate group, hospitalists have a
      narrower focus that allows them to achieve better length of stay with lower costs
      and potentially improve the quality and safety of inpatient care as demonstrated
      in the studies referenced in this essay. Along with narrower focus the increased
      experience of treating inpatient illness and increased in-hospital availability
      contribute to the benefits described for hospitalist programs. Whether
      hospitalists will succeed as outlined above and how this group will function
      within our South Carolina healthcare system is up to the local leaders and state
      policy makers. Dr Carolyn Clancy, the Director of AHRQ pointed out in her Keynote
      Address to the Society of Hospital Medicine in May 2006 that "we will need you to
      expand 2 or 3 times to address this issue of quality". We make the following
      recommendations to incorporate these potentially beneficial systems: 1)
      Implemented hospital systems should follow the guidelines in the April 2005
      Pediatrics policy statement. It is essential that systems be voluntary and
      private physicians reserve the right to admit to the hospital since many office
      based pediatricians have the skills and desire to continue inpatient care. 2)
      Medicaid and private providers should recognize the safety net function of
      hospitalist programs and the increasing complexity and acuity of pediatric
      inpatients and should reimburse pediatric inpatient care at or above Medicare
      rates to insure that hospitalist programs are financially sustainable. 3)
      Hospitalists should act as leaders in safety and quality initiatives including
      the use of evidence-based practice. 4) Implementation of hospitalist programs
      should be done in collaboration with local physicians to insure success and
      acceptance. In summary, hospitalists programs are growing and defining new
      paradigms in the national healthcare system. The programs can offer numerous
      benefits to patients, hospitals, and payers.

PMID- 18333578
TI  - Off-label prescribing of medications for children.
AB  - Off-label prescription of approved drugs is common and often necessary in
      pediatric practice. Off-label prescription of approved drugs does not constitute
      malpractice and is not considered experimental therapy. Pediatric providers
      should endeavor to become familiar with commonly prescribed off-label drugs and
      strive to limit their prescribing to the drugs with existing pediatric
      experience. Pediatric providers may choose to inform parents that a drug is being
      used in an off-label manner, but informed consent is not required.

PMID- 18333579
TI  - Exploration of the virtues.

PMID- 18333580
TI  - The seven basic virtues in medicine: summing up.

PMID- 18333581
TI  - Codetron as adjunctive treatment in pediatric patients following spinal surgery.

PMID- 18333582
TI  - Making optimum use of Web-based resources in an office practice--enabling
      evidence-based medicine for busy physicians.

PMID- 18333583
TI  - Are disease mortality rates and survival rates complementary? If not, can they be
      related? Which is more relevant?
AB  - The relationship of mortality to survival is complicated and this paper suggests
      the two rates should both be defined for each condition or illness in order
      better to appreciate the projected real impact of the illness in question on
      patients. And if available conventional mortality data are "old" or not yet
      available, the above derived formula offers an alternate method of determining
      the mortality rate, provided one knows or can learn the prevalence of the illness
      and already has the more often published survival data. Physician lead
      discussions with patients today regarding such issues of survival and mortality
      often lead to the consideration of whether to undertake increasingly more
      invasive and/or expensive and complicated early diagnostic studies and/or
      interventions. The concerned patients and their families are many times
      relatively medically unsophisticated and not unexpectedly fearful. Both states of
      mind render them less able to understand complicated and, often to them, abstruse
      sounding explanations of their options. They most often default to the
      recommendation of their physician(s) and rely ultimately on sound analysis of the
      risks and probabilities of the alternatives by their doctor(s) to craft a course
      of investigation and therapy for them that is most likely to result in their
      improved outcome based on his or her judgment and experience. They trust the
      physician to optimize a plan for them. Therefore, in light of misleading
      conclusions a physician might draw by considering changes in survival statistics
      alone, it is worthwhile that he or she also understand and factor in mortality
      data that would follow in the wake of pursuing a recommended strategy. It is
      offered that use of the above derived formula: M = (1-S)*P provides a relatively
      simple tool for retrieving this more defining mortality statistic that is
      otherwise frequently more difficult to locate and is often not included in
      published reports of promising new investigative or therapeutic strategies. I
      propose, having personally accumulated more than desired patient perspective, it
      is essential for South Carolina physicians charged with responsibility of
      advising their patients on major and difficult choices understand the importance
      of and difference between these two outcome rates derived from both diagnostic
      studies and therapeutic interventions. The significance of these ratios or rates
      to and for the patient, especially if they conflict, should be conveyed to
      patients at the appropriate conversational level based on the education and
      understanding of the patient and his/her family. By comprehending and explaining
      both these ratios in layman's terms appropriate to each individual patient, a
      clearer understanding of the merit or lack thereof of the available options for
      that individual can be attained.

PMID- 18333584
TI  - Leukocytoclastic vasculitis due to hydrochlorthiazide.

PMID- 18333585
TI  - Health care reform: the case for communitarianism.

PMID- 18333586
TI  - The literature search: an essential skill.

PMID- 18333587
TI  - The ultimate gift.

PMID- 18333588
TI  - Our stance on the health care crisis.

PMID- 18333589
TI  - Service utilization comparison of South Carolina Medicaid fee-for-service (FFS),
      Physician Enhanced Plan (PEP) and Health Maintenance Organization (HMO) models.

PMID- 18333590
TI  - Infant health outcomes differ notably among Medicaid insurance models: evidence
      of a successful case management program in South Carolina.

PMID- 18333591
TI  - Infant health care costs for Medicaid-insured infants in South Carolina enrolled
      in three insurance plans from birth to 24 months.

PMID- 18333592
TI  - Why Medicaid managed care is right for South Carolina.

PMID- 18333593
TI  - Prevalence and features of palato-radicular grooves: an in-vitro study.
AB  - The presence of a morphological defect called a palato-radicular groove (PRG) is
      considered to be an important contributing factor to the development of localized
      chronic periodontitis, for it favors the accumulation and proliferation of
      bacterial plaque deep into the periodontium. This anomaly affects maxillary
      incisors, especially lateral incisors. The prevalence and different morphologic
      conditions of the PRG were evaluated in 376 maxillary lateral and central
      incisors. The teeth were evaluated by a single examiner, considering their
      presence, localization, origin of formation, extension and depth in millimeters,
      using a magnifying glass, a precision pachymeter and a millimeter-scaled
      periodontal probe. Results showed a higher prevalence in lateral incisors
      (11.1%), with higher prevalence in proximal localization (62.8%), origination
      from central fossa (57.1%) and predominance in oblique trajectory (62.8%). Of all
      these teeth, only 8.6% of PRGs reached the root apex, while 97.1% were considered
      as flat (< 1 mm). Thus, in the presence of a PRG, periodontal pathologic
      conditions could be more severe in proximal faces, reaching in a few cases the
      tooth apex and the pulp canal.

PMID- 18333594
TI  - Full mouth disinfection versus quadrant debridement: the clinician's choice.
AB  - Traditional periodontal therapy is subgingival debridement with maintenance of
      good oral hygiene. This approach is either definitive or the initial phase before
      surgical therapy in severe cases of periodontitis. Mechanical therapy, either
      hand instrumentation or ultrasonic debridement, is the most common therapy for
      periodontitis and its success is well documented (Badersten et al. 1984). This
      non-surgical therapy involves considerable amounts of time, a high level of
      operator skill and dedication, and some unavoidable discomfort for the patient.
      It has often been remarked that the time taken for periodontal therapy of severe
      periodontitis cases exceeds that needed for cardiac arterial bypass surgery.
      Quirynen et al. (1995) re-introduced the one-stage full-mouth disinfection and
      compared the clinical and microbiological effects of this treatment strategy
      (FMRP) with the widespread practice of quadrant scaling and root planing at 2
      week intervals (QRP). The rationale behind their treatment strategy was to
      prevent re-infection of the treated sites from the remaining untreated pockets
      and intra-oral niches. The results revealed a significant reduction in pocket
      depth for the FMRP over QRP group for deep pockets. Quirynen et al. (2000)
      concluded that the elimination of the periodontopathogens in addition to the
      possible host response benefits after the one-stage full-mouth therapy is the
      effective aspect of this therapy rather than oral chlorhexidine disinfection.
      Recently, Kinane's group in Glasgow failed to demonstrate differences in the
      clinical, microbiological or immunological outcome between QRP and FMRP. FMRP was
      well tolerated by patients and these authors concluded that the clinician should
      select the treatment modality based on practical considerations related to
      patient preference and clinical workload. Koshy et al. (2005) re-analysed the
      effects of FMRP and QRP using ultrasonics and concluded that either full-mouth or
      quadrant ultrasonic debridement are just as effective.

PMID- 18333595
TI  - Necrotizing periodontal diseases in HIV-seropositive subjects: pathogenic
      mechanisms.
AB  - Necrotizing gingivitis (NG) is a well-known periodontal condition characterized
      by marginal gingival necrosis, bleeding and pain. Necrotizing periodontitis is an
      extension of NG into the periodontal attachment apparatus, and the two stages are
      referred to collectively as necrotizing periodontal diseases (NPD). Necrotizing
      periodontal diseases in HIV-seropositive subjects are similar with regard to the
      spectrum of periodontopathic bacteria, the clinical manifestations, the natural
      course and the response to treatment when compared to NPD in HIV-seronegative
      subjects. However, in the former group, there is an increase in the prevalence of
      candidal species and herpesviruses in the subgingival plaque and gingival biopsy
      specimens. In the periodontal tissues, spirochaetes, activated herpesviruses,
      Candida species and HIV have the capability of deregulating host innate and
      adaptive immune responses and of stimulating host inflammatory reactions, and may
      therefore explain the greater prevalence of NPD in HIV-seropositive subjects
      compared to immunocompetent subjects.

PMID- 18333596
TI  - Radiographic assessment of periodontitis in African-Americans with Down syndrome.
AB  - OBJECTIVE: Down syndrome (DS) is a neurodevelopmental genetic disorder affecting
      millions of Americans. Previous studies, mainly in Caucasians, have shown
      periodontitis to be a major oral health problem among DS patients. Other research
      has shown that African-Americans (AA) are more susceptible to periodontitis than
      Caucasians. Our objective was to determine if DS negatively affects the already
      impaired periodontal status of AAs. METHODS: Radiographic alveolar bone levels
      were used to determine periodontal status. Full-mouth series of intraoral
      periapical (PA) radiographs of 25 AA DS patients (age range 18-64 years, 36%
      males) were randomly selected from a special care dental center for the
      handicapped. PA radiographs of 25 AA mentally challenged (MC) non-Down patients
      were also selected from the same center. MC patients were matched to DS patients
      on variables of race, age, sex, socioeconomic status and institutionalized care.
      All periapical radiographs were taken with a long cone paralleling technique
      under normal clinical practice conditions. Under standardized viewing conditions,
      the distance from the cementoenamel junction to the interproximal alveolar crest
      on both the mesial and distal surfaces of each fully erupted permanent tooth
      present was measured. A paired samples t-test was used to compare the
      radiographic bone levels of DS and MC subjects. RESULTS: All subjects showed
      sites with bone loss > or = 3 mm. Whole mouth mean (SD) bone level for DS
      subjects was 3.0 (1.5) mm and for MC subjects it was 1.9 (1.1) mm, p = 0.001.
      This finding was replicated in the various regions in the mouth where DS patients
      showed greater bone loss than MC patients in anterior regions (incisors and
      canines, p = 0.001), in posterior regions (molars and premolars, p = 0.007), in
      maxillary regions (p = 0.001) and in mandibular regions (p = 0.005). CONCLUSIONS:
      Periodontitis is a problem in AA patients. Adding the genetic disorder of DS to
      AA race imposes additional risks for periodontitis.

PMID- 18333597
TI  - Clinical application of erbium:YAG laser in periodontology.
AB  - Various lasers have been introduced for the treatment of oral diseases and their
      applications in dental clinics have become a topic of much interest among
      practitioners. Technological advances and improvements have increased the choices
      of the available laser systems for oral use. Among them, a recently developed
      erbium-doped:yttrium aluminum garnet (Er:YAG) laser system possesses suitable
      characteristics for oral soft and hard tissue ablation. Due to its high
      absorption in water, an effective ablation with a very thin surface interaction
      occurs on the irradiated tissues without any major thermal damage to the
      irradiated and surrounding tissues. In the field of periodontics, the application
      of Er:YAG laser for periodontal hard tissue has begun with studies from Japanese
      and German researchers. Several in vitro and clinical studies have already
      demonstrated an effective application of the Er:YAG laser for calculus removal
      and decontamination of the diseased root surface in periodontal non-surgical and
      surgical procedures. However, further studies are required to better understand
      the various effects of Er:YAG laser irradiation on biological tissues for its
      safe and effective application during periodontal and implant therapy. Randomized
      controlled clinical trials and more basic studies have to be encouraged and
      performed to confirm the status of Er:YAG laser treatment as an adjunct or
      alternative to conventional mechanical periodontal therapy. In this paper, the
      advantages and current clinical applications of this laser in periodontics and
      implant dentistry are summarized based on current scientific evidence.

PMID- 18333598
TI  - Local delivery of chlorhexidine gluconate in patients with aggressive
      periodontitis.
AB  - The aim of this randomized, controlled, single-blinded trial was to evaluate the
      effectiveness of a biodegradable chlorhexidine chip as an adjunctive therapy to
      scaling and root planing. Eleven consecutive patients with aggressive
      periodontitis were recruited for this study. Each volunteer provided four sites
      with probing depth > or = 5 mm. Two sites received scaling and root planing (SRP)
      and placement of the chlorhexidine chip (PC), and the other two sites received
      scaling and root planing only. The clinical outcomes were measured at baseline, 6
      weeks and 3 months after treatment. All patients completed the trial. None of the
      volunteers reported any adverse effect. Both groups showed a significant
      reduction in periodontal pocket depth (PPD) and gain in clinical attachment level
      (CAL) after treatment. However, there were no significant differences in the
      clinical parameters between the groups after 6 weeks and after 3 months. Sites
      presenting probing depths > or = 8 mm at baseline treated with SRP + PC
      demonstrated greater reduction in PPD and a greater CAL gain than sites treated
      with SRP alone after 6 weeks and after 3 months. The authors concluded that the
      adjunctive use of the biodegradable chlorhexidine chip resulted in greater
      reduction of PPD and additional gain in CAL in deep pockets (PPD > or = 8 mm) in
      patients with aggressive periodontitis when compared to scaling and root.

PMID- 18333599
TI  - The influence of dental unit waterline cleaners on composite-to-dentin bond
      strengths.
AB  - BACKGROUND: One approach to controlling dental unit waterline (DUWL)
      contamination by microorganisms is the addition of chemical cleaners to the
      treatment water. Yet, there is concern that these cleaners might affect the
      bonding of resin-based composites to enamel and dentin. The authors evaluated the
      influence of DUWL cleaners on composite-to-dentin bond strengths. METHODS: The
      authors tested the strength of resin-based composite bonded to dentin in
      specimens treated with distilled water (control) or one of four cleaners. They
      tested a total-etch adhesive, a self-etching primer/adhesive and an experimental
      self-etching primer/ adhesive. The authors stored the specimens for 24 hours at
      37 C and tested them to determine their bond strengths. RESULTS: The mean shear
      bond strengths (SBSs) varied according to the cleaner and adhesive used, ranging
      from 14.7 to 21.9 megapascals. However, the authors found no statistically
      significant differences and/or interactions between mean SBSs of specimens
      treated with the various DUWL cleaners and adhesives (P > or = .05). CONCLUSIONS:
      The tested DUWL cleaners did not significantly influence composite-to-dentin bond
      strengths for the total-etch adhesive and self-etching primer/adhesives used in
      this study. CLINICAL IMPLICATIONS. The conclusions imply that bonding of resin
      based composites to dentin is not affected by the cleaners tested when they are
      used to treat DUWL contamination.

PMID- 18333600
TI  - Fabricating an in-office mouth guard.

PMID- 18333601
TI  - The little cranberry that packs a big punch.

PMID- 18333602
TI  - Air Force dental assistants in forensic dentistry.

PMID- 18333603
TI  - Cancer vaccines: an overview.
AB  - The long-held hope that vaccination strategies might be effective against cancer
      has motivated numerous attempts over the past century to put the idea to test in
      the clinic. Although the generally disappointing results have cast a long shadow
      over the field, advances in cancer immunology growing on the remarkable insights
      from basic immunology provide a strong foundation and powerful new tools to guide
      current attempts to fashion effective cancer vaccines. This review covers the
      scientific basis and rationale for cancer vaccines, the challenges involved in
      assembling the many ingredients going into the construction of cancer vaccines,
      and the daunting obstacles confronting academic investigators wanting to transfer
      their discoveries into the clinical arena. The Cancer Vaccine Collaborative
      (CVC), a partnership between the Cancer Research Institute and the Ludwig
      Institute for Cancer Research, represents a new academic model for developing,
      coordinating, conducting, and monitoring cancer vaccine trial. NY-ESO-1, a
      prototype cancer-testis (CT) antigen having strong spontaneous humoral and
      cellular immunogenicity, has been chosen as the initial CVC vaccine target, and
      the current status of NY-ESO-1 vaccine trials carried at the multiple CVC sites
      around the world is discussed.

PMID- 18333604
TI  - Preparation and in vitro evaluation of novel lipopeptide transfection agents for
      efficient gene delivery.
AB  - Gene therapy by delivery of nonviral expression vectors is highly desirable, due
      to their safety, stability, and suitability for production as bulk
      pharmaceuticals. However, low transfection efficiency remains a limiting factor
      in application on nonviral gene delivery. Despite recent advances in the field,
      there are still major obstacles to overcome. In an attempt to construct more
      efficient nonviral gene delivery vectors, we have designed a series of novel
      lipopeptide transfection agents, consisting of an alkyl chain, one cysteine, 1 to
      4 histidine and 1 to 3 lysine residues. The lipopeptides were designed to
      facilitate dimerization (by way of the cysteine residues), DNA binding at neutral
      pH (making use of charged lysine residues), and endosomal escape (by way of
      weakly basic histidine residues). DNA/lipopeptide complexes were evaluated for
      their biophysical properties and transfection efficiencies. The number and
      identity of amino acids incorporated in the lipopeptide construct affected their
      DNA/lipopeptide complex forming capacity. As the number of lysine residues in the
      lipopeptide increased, the DNA complexes formed became more stable, had higher
      zeta potential (particle surface charge), and produced smaller mean particle
      sizes (typically 110 nm at a charge ratio of 5.0 and 240 nm at a charge ratio of
      1.0). The effect of inclusion of histidines in the lipopeptide moiety had the
      opposite effect on complex formation to lysine, but was necessary for high
      transfection efficiency. In vitro transfection studies in COS-7 cells revealed
      that the efficiency of gene delivery of the luciferase encoding plasmid, pCMV
      Luc, mediated by all the lipopeptides, was much higher than poly(L-lysine) (PLL),
      which has no endosomal escape system, and in two cases was slightly higher than
      that of branched polyethylenimine (PEI). Lipopeptides with at least two lysine
      residues and at least one histidine residue produced spontaneous transfection
      complexes with plasmid DNA, indicating that endosomal escape was achieved by
      incorporation of histidine residues. These low molecular weight peptides can be
      readily synthesized and purified and offer new insights into the mechanism of
      action of transfection complexes.

PMID- 18333606
TI  - Bis-(-)-nor-meptazinols as novel nanomolar cholinesterase inhibitors with high
      inhibitory potency on amyloid-beta aggregation.
AB  - Bis-(-)-nor-meptazinols (bis-(-)-nor-MEPs) 5 were designed and synthesized by
      connecting two (-)-nor-MEP monomers with alkylene linkers of different lengths
      via the secondary amino groups. Their acetylcholinesterase (AChE) inhibitory
      activities were more greatly influenced by the length of the alkylene chain than
      butyrylcholinesterase (BChE) inhibition. The most potent nonamethylene-tethered
      dimer 5h exhibited low-nanomolar IC 50 values for both ChEs, having a 10 000-fold
      and 1500-fold increase in inhibition of AChE and BChE compared with (-)-MEP.
      Molecular docking elucidated that 5h simultaneously bound to the catalytic and
      peripheral sites in AChE via hydrophobic interactions with Trp86 and Trp286. In
      comparison, it folded in the large aliphatic cavity of BChE because of the
      absence of peripheral site and the enlargement of the active site. Furthermore,
      5h and 5i markedly prevented the AChE-induced Abeta aggregation with IC 50 values
      of 16.6 and 5.8 microM, similar to that of propidium (IC 50 = 12.8 microM), which
      suggests promising disease-modifying agents for the treatment of AD patients.

PMID- 18333607
TI  - Conformational analysis and receptor docking of N-[(1S,2S)-3-(4-chlorophenyl)-2
      (3-cyanophenyl)-1-methylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2
      yl]oxy}propanamide (taranabant, MK-0364), a novel, acyclic cannabinoid-1 receptor
      inverse agonist.
AB  - X-ray crystallographic, NMR spectroscopic, and computational studies of
      taranabant afforded similar low-energy conformers with a significant degree of
      rigidity along the C11-N13-C14-C16-C17 backbone but with more flexibility around
      bonds C8-C11 and C8-O7. Mutagenesis and docking studies suggested that taranabant
      and rimonabant shared the same general binding area of CB1R but with significant
      differences in detailed interactions. Similar to rimonabant, taranabant
      interacted with a cluster of aromatic residues (F(3.36)200, W(5.43)279,
      W(6.48)356, and Y(5.39)275) through the two phenyl rings and with F(2.57)170 and
      L(7.42)387 through the CF 3-Pyr ring. The notable distinction between taranabant
      and rimonabant was that taranabant was hydrogen-bonded with S(7.39)383 but not
      with K(3.28)192, while rimonabant was hydrogen-bonded with K(3.28)192 but not
      with S(7.39)383. The strong hydrogen bonding between the amide NH of taranabant
      and hydroxyl of S(7.39)383 was key to the superior affinity of taranabant to
      CB1R.

PMID- 18333609
TI  - Four isomorphous phosphates AM3P4O14 (A = Sr, Ba; M = Co, Mn) with
      antiferromagnetic-antiferromagnetic-ferromagnetic trimerized chains, showing 1/3
      quantum magnetization plateaus only in the manganese(II) system.
AB  - The four new phosphates BaCo3P4O14 (1), SrCo3P4O14 (2), BaMn3P4O14 (3), and
      SrMn3P4O14 (4) were hydrothermally synthesized and characterized structurally and
      magnetically. They are isostructural with ANi3P4O14 (A = Ca, Sr, Pb, Ba),
      crystallizing in the monoclinic space group P2(1)/c. The CoO6 (or MnO6) octahedra
      share edges to from zigzag chains along the b axis, which are further
      interconnected by P2O7 groups into a three-dimensional structure. Preliminary
      magnetic measurements on powder samples indicate that 1, 2, and 4 are spin-canted
      antiferromagnets and 3 is a pure antiferromagnet at low field; long-range
      orderings were established respectively at T critical approximately 8.2 K for 1,
      6.5 K for 2, and 2.6 K for both 3 and 4; field-induced spin-flop-like transitions
      occur respectively at Hc approximately 25 kOe for 1, 4 kOe for 2, 3 kOe for 3,
      and 0.7 kOe for 4. Interestingly, together with the known Ni analogues, they all
      apply the same antiferromagnetic-antiferromagnetic-ferromagnetic (AAF) trimerized
      chain model, whereas the 1/3 quantum magnetization plateau only appears in the Mn
      system. By qualitative analysis, we conclude that the appearance of quantum
      magnetization plateaus in the AAF chain compounds requires both good 1D
      characteristics and strong AF intrachain interactions.

PMID- 18333608
TI  - Comprehensive mechanistic analysis of hits from high-throughput and docking
      screens against beta-lactamase.
AB  - High-throughput screening (HTS) is widely used in drug discovery. Especially for
      screens of unbiased libraries, false positives can dominate "hit lists"; their
      origins are much debated. Here we determine the mechanism of every active hit
      from a screen of 70,563 unbiased molecules against beta-lactamase using
      quantitative HTS (qHTS). Of the 1,274 initial inhibitors, 95% were detergent
      sensitive and were classified as aggregators. Among the 70 remaining were 25
      potent, covalent-acting beta-lactams. Mass spectra, counter-screens, and
      crystallography identified 12 as promiscuous covalent inhibitors. The remaining
      33 were either aggregators or irreproducible. No specific reversible inhibitors
      were found. We turned to molecular docking to prioritize molecules from the same
      library for testing at higher concentrations. Of 16 tested, 2 were modest
      inhibitors. Subsequent X-ray structures corresponded to the docking prediction.
      Analog synthesis improved affinity to 8 microM. These results suggest that it may
      be the physical behavior of organic molecules, not their reactivity, that
      accounts for most screening artifacts. Structure-based methods may prioritize
      weak-but-novel chemotypes in unbiased library screens.

PMID- 18333610
TI  - Visible light-driven electron transfer and hydrogen generation catalyzed by
      bioinspired [2Fe2S] complexes.
AB  - Complexes [{(mu-SCH2)2NCH2C6H5}{Fe(CO)2L(1)}{Fe(CO)2L(2)}] (L(1) = CO, L(2) =
      P(Pyr) 3, 2; L(1) = L(2) = P(Pyr)3, 3) were prepared, which have the lowest
      reduction potentials for the mono- and double-CO-displaced diiron complexes
      reported so far. Hydrogen evolution, driven by visible light, was successfully
      observed for a three-component system, consisting of a ruthenium polypyridine
      complex, the biomimetic model complex 2 or 3, and ascorbic acid as both electron
      and proton donor in CH3CN/H2O. The electron transfer from photogenerated
      Ru(bpy)3(+) to 2 or 3 was detected by laser flash photolysis. Under optimal
      conditions, the total turnover number for hydrogen evolution was 4.3 based on 2
      and 86 based on Ru(bpy)3(2+) in a three-hour photolysis.

PMID- 18333611
TI  - Quantum chemical study of trivalent group 12 fluorides.
AB  - In view of the recent experimental observation of the existence of tetravalent Hg
      (IV) in HgF 4, a quantum chemical study of various trivalent group 12 M(III)
      fluoride complexes has been carried out. The M-F bonds in neutral MF 3 are
      relatively weak, making these species unlikely targets. Some additional stability
      can be obtained by dimerizing HgF3 to Hg2F6, which has a doubly fluorine-bridged
      triplet ground state. Anionic [MF4]- and [MF5]2- species are found to be more
      stable toward F2 elimination and M-F bond breaking than neutral MF 3.

PMID- 18333612
TI  - Self-assembly of organic-inorganic hybrid materials constructed from eight
      connected coordination polymer hosts with nanotube channels and polyoxometalate
      guests as templates.
AB  - Two polyoxometalate-templated organic-inorganic hybrid porous frameworks, namely,
      [Cu2(H2O)2(bpp)2Cl][PM12O40].approximately 20H2O (for 1, M = W; for 2, M = Mo;
      bpp = 1,3-bis(4-pyridyl)propane), were self-assembly obtained and structurally
      determined by elemental analyses, inductively coupled plasma analyses, infrared
      spectroscopy, and single-crystal X-ray diffraction analyses. Single-crystal X-ray
      analysis of these crystals revealed that both of the structures are constructed
      from eight-connected three-dimensional coordination polymer hosts
      [Cu2(H2O)2(bpp)2Cl]n(3n+) and ball-shaped Keggin-type guests [PM12O40]n(3n-) as
      templates. The polymer hosts resulted from a bcc-type framework with nanotubes,
      and the nanotubes can be regarded as a tetra-stranded helix structure.
      Furthermore, compounds 1 and 2 exhibit photoluminescent properties at ambient
      temperature, and the compound 2 bulk-modified carbon paste electrode ( 2-CPE)
      displays good electrocatalytic activity toward the reduction of nitrite.

PMID- 18333613
TI  - Terminal hydride in [FeFe]-hydrogenase model has lower potential for H2
      production than the isomeric bridging hydride.
AB  - Protonation of the symmetrical tetraphosphine complexes Fe2(S2CnH2n)(CO)2(dppv)2
      afforded the corresponding terminal hydrides, establishing that even symmetrical
      diiron(I) dithiolates undergo protonation at terminal sites. The terminal hydride
      [HFe2(S2C3H6)(CO)2(dppv)2](+) was found to catalyze proton reduction at
      potentials 200 mV milder than the isomeric bridging hydride, thereby establishing
      a thermodynamic advantage for catalysis operating via terminal hydride. The
      azadithiolate protonates to afford, [Fe2[(SCH2)2NH2](CO)2(dppv)2](+),
      [HFe2[(SCH2)2NH](CO)2(dppv)2](+), and [HFe2[(SCH2)2NH2](CO)2(dppv)2](2+),
      depending on conditions.

PMID- 18333614
TI  - Purification and partial characterization of Lactobacillus species SK007 lactate
      dehydrogenase (LDH) catalyzing phenylpyruvic acid (PPA) conversion into
      phenyllactic acid (PLA).
AB  - Phenyllactic acid (PLA) is a novel antimicrobial compound synthesized by lactic
      acid bacteria (LAB), and its production from phenylpyruvic acid (PPA) is an
      effective approach. In this work, a lactate dehydrogenase (LDH), which catalyzes
      the reduction of PPA to PLA, has been purified to homogeneity from a cell-free
      extract of Lactobacillus sp. SK007 by precipitation with ammonium sulfate, ion
      exchange, and gel filtration chromatography. The purified enzyme had a dimeric
      form with a molecular mass of 78 kDa (size exclusion chromatography) or 39 kDa
      (SDS-PAGE). The ratio of enzyme activity with PPA to that with pyruvate being
      almost invariable at every purification step indicated that, in Lactobacillus sp.
      SK007, LDH is responsible for the conversion of PPA into PLA. HPLC profiles of
      PPA transformation into PLA by growing cells, cell-free extract, and purified LDH
      of Lactobacillus sp. SK007 were also investigated. Results showed that the
      presence of NADH was found to be necessary for the enzymatic production of PLA
      from PPA. The purified LDH displayed optimal activity for PPA at pH 6.0 and 40
      degrees C. The Km values of the enzyme for PPA and pyruvate were 1.69 and 0.32
      mM, respectively. Moreover, because other screened LAB strains exhibiting
      relatively high LDH activity toward PPA produced also considerable amounts of
      PLA, LDH activity for PPA could be therefore used as a screening marker for PLA
      producing LAB.

PMID- 18333615
TI  - Sex pheromone of browntail moth, Euproctis chrysorrhea (L.): synthesis and field
      deployment.
AB  - The browntail moth, Euproctis chrysorrhea (L.), is native to Eurasia, where
      periodic outbreaks result in defoliation of forest, shade, and ornamental trees.
      In addition to the damage caused by defoliation, human contact with larval
      urticating hairs often results in severe dermatitis. Hence, tools for monitoring
      and controlling the moth populations are desirable. The female-produced sex
      pheromone of the browntail moth was identified previously, but the synthesis had
      not been published. This paper reports the synthesis of the pheromone of the
      browntail moth, (7Z,13Z,16Z,19Z)-docosatetraenyl isobutyrate, using in a key step
      a Wittig olefination of (6Z)-13-(tetrahydo-2H-pyran-2-yloxy)tridecenal. Field
      trapping studies were conducted with rubber septa and string formulations of the
      pheromone and included dose-response, pheromone purity, and dispenser-aging
      trials. It was found that traps baited with 250 microg of pheromone of 91-94%
      isomeric purity (main impurity presumably being the 13E isomer) on rubber septa
      are suitable for monitoring moth populations during the entire flight season.

PMID- 18333616
TI  - Preparation of high-purity fructo-oligosaccharides by Aspergillus japonicus beta
      fructofuranosidase and successive cultivation with yeast.
AB  - The short-chain FOSs with high purity were prepared using a two-step strategy:
      Aspergillus japonicus extracellular beta-fructofuranosidase-catalyzed synthesis
      of FOSs followed by cultivation with Pichia pastoris (P. pastoris). The higher
      FOSs content was obtained after 8 h under the catalysis of beta
      fructofuranosidase at pH 5.5 and 55 degrees C. Successive P. pastoris cultivation
      exhausts almost all monosugars in 12 h at 30 degrees C, which increases the
      purity of FOSs, and also recovers beta-fructofuranosidase activity by ceasing the
      inhibition of glucose from catalysis of the enzyme, yielding more FOSs. Finally,
      the FOSs purity was increased from 56.55 to 84.45% (26.47% 1-kestose and 57.98%
      nystose).

PMID- 18333617
TI  - Kinetics of acid hydrolysis of water-soluble spruce O-acetyl galactoglucomannans.
AB  - Water-soluble O-acetyl galactoglucomannan (GGM) is a softwood-derived
      polysaccharide, which can be extracted on an industrial scale from wood or
      mechanical pulping waters and now is available in kilogram scale for research and
      development of value-added products. To develop applications of GGM, information
      is needed on its stability in acidic conditions. The kinetics of acid hydrolysis
      of GGM was studied at temperatures up to 90 degrees C in the pH range of 1-3.
      Molar mass and molar mass distribution were determined using size exclusion
      chromatography with multiangle laser light scattering and refractive index
      detection. The molar mass of GGM decreased considerably with treatment time at
      temperatures above 70 degrees C and pH below 2. The molar mass distribution
      broadened with hydrolysis time. A first-order kinetic model was found to match
      the acid hydrolysis. The reaction rate constants at various pH values and
      temperatures were calculated on the basis of the first-order kinetic model.
      Furthermore, the activation energy, E, was obtained from the Arrhenius plot. The
      activation energy E was 150 kJ mol (-1) for acid hydrolysis of spruce GGM. The
      apparent rate constant during acid hydrolysis increased by a factor of 10 with a
      decrease in pH by 1 unit, regardless of temperature. In addition, gas
      chromatography and matrix-assisted laser desorption/ionization time-of-flight
      mass spectrometry were applied to study the released GGM monomers and oligomers.

PMID- 18333618
TI  - Influence of B-ring hydroxylation on interactions of flavonols with bovine serum
      albumin.
AB  - The B-ring substitution pattern of flavonols is a significant structural feature
      for their function as free radical scavengers and antioxidants. In this paper,
      four differently substituted B-ring hydroxylation flavonols (galangin,
      kaempferol, quercetin, and myricetin) and a flavonol glycoside (quercitrin) were
      studied for their ability to bind BSA by quenching the protein intrinsic
      fluorescence. From the spectra obtained, the biomolecular quenching constants,
      the apparent static binding constants, and the binding site values were
      calculated. The B-ring hydroxylation of flavonols significantly affected the
      binding/quenching process; in general, the binding affinity increased with the
      number of hydroxyl groups on the B-ring. The binding constants ( Ka) were
      determined as myricetin (4.90 x 10(8) L/mol) > quercetin (3.65 x 10(7) L/mol) >
      kaempferol (2.57 x 10(6) L/mol) > galangin (6.43 x 10(5) L/mol). The glycoside
      substitute at the C-ring position decreased the binding affinity. The
      chromatographic retention factor ( K') and logarithms of apparent partition
      coefficient (log Kow) were linear to the logarithms of apparent binding constants
      (log Ka) for flavonols with increasing hydroxyl groups on the B-ring. These
      results showed that the hydrogen bond force play an important role in binding
      flavonols to BSA. These results are also in agreement with the generally accepted
      structure-dependent free radical scavenger and antioxidant abilities of
      flavonols.

PMID- 18333619
TI  - Strain improvement of recombinant Escherichia coli for efficient production of
      plant flavonoids.
AB  - Plant flavonoid polyphenols continue to find increasing pharmaceutical and
      nutraceutical applications; however their isolation, especially of pure
      compounds, from plant material remains an underlying challenge. In the past
      Escherichia coli, one of the most well-characterized microorganisms, has been
      utilized as a recombinant host for protein expression and heterologous
      biosynthesis of small molecules. However, in many cases the expressed protein
      activities and biosynthetic efficiency are greatly limited by the host cellular
      properties, such as precursor and cofactor availability and protein or product
      tolerance. In the present work, we developed E. coli strains capable of high
      level flavonoid synthesis through traditional metabolic engineering techniques.
      In addition to grafting the plant biosynthetic pathways, the methods included
      engineering of an alternative carbon assimilation pathway and the inhibition of
      competitive reaction pathways in order to increase intracellular flavonoid
      backbone precursors and cofactors. With this strategy, we report the production
      of plant-specific flavanones up to 700 mg/L and anthocyanins up to 113 mg/L from
      phenylpropanoic acid and flavan-3-ol precursors, respectively. These results
      demonstrated the efficient and scalable production of plant flavonoids from E.
      coli for pharmaceutical and nutraceutical applications.

PMID- 18333620
TI  - The liquid-liquid interface as a medium to generate nanocrystalline films of
      inorganic materials.
AB  - Unlike the air-water interface, the organic-aqueous (liquid-liquid) interface has
      not been exploited sufficiently for materials synthesis. In this Account, we
      demonstrate how ultrathin nanocrystalline films of metals such as gold and silver
      as well as of inorganic materials such as semiconducting metal chalcogenides
      (e.g., CdS, CuS, CdSe) and oxides are readily generated at the liquid-liquid
      interface. What is particularly noteworthy is that single-crystalline films of
      certain metal chalcogenides are also obtained by this method. The as-prepared
      gold films at the toluene-water interface comprise fairly monodisperse
      nanocrystals that are closely packed, the nature and properties of the films
      being influenced by various reaction parameters such as reaction temperature,
      time, reactant concentrations, mechanical vibrations, and the viscosity of the
      medium. The surface plasmon band of gold is markedly red-shifted in the films due
      to electronic coupling between the particles. The shift of the surface plasmon
      band of the Au film toward higher wavelengths with an accompanying increase in
      intensity as a function of reaction time marks the growth of the film. Depending
      on the reaction temperature, the Au films show interesting electrical transport
      properties. Films of metals such as gold are disintegrated by the addition of
      alkanethiols, the effectiveness depending on the alkane chain length, clearly
      evidenced by shifts of the surface plasmon bands. A time evolution study of the
      polycrystalline Au and CdS films as well as the single-crystalline CuS films is
      carried out by employing atomic force microscopy. X-ray reflectivity studies
      reveal the formation of a monolayer of capped clusters having 13 gold atoms each,
      arranged in a hexagonal manner at the toluene-water interface. The measurements
      also reveal an extremely small value of the interfacial tension. Besides
      describing features of such nanocrystalline films and their mode of formation,
      their rheological properties have been examined. Interfacial rheological studies
      show that the nanocrystalline film of Ag nanoparticles, the single-crystalline
      CuS film, and the multilayered CdS film exhibit a viscoelastic behavior strongly
      reminiscent of soft-glassy systems. Though both CuS and CdS films exhibit a
      finite yield stress under steady shear, the CdS films are found to rupture at
      high shear rates. An important advantage of the study of materials formed at the
      liquid-liquid interface is that it provides a means to investigate the interface
      itself. In addition, it enables one to obtain substrate-free single-crystalline
      films of materials.

PMID- 18333621
TI  - Experimental and theoretical studies suggesting the possibility of metallic boron
      nitride edges in porous nanourchins.
AB  - We first describe the synthesis of novel and highly porous boron nitride (BN)
      nanospheres (100-400 nm o.d.) that exhibit a rough surface consisting of open BN
      nanocones and corrugated BN ribbons. The material was produced by reacting B2O3
      with nanoporous carbon spheres under nitrogen at ca. 1750 degrees C. The BN
      nanospheres were characterized using scanning electron microscopy, high
      resolution electron microscopy, and electron energy loss spectroscopy. The porous
      BN spheres show relatively large surface areas of ca. 290 m2/g and exhibit
      surprisingly stable field emission properties at low turn-on voltages (e.g., 1
      1.3 V/microm). We attribute these outstanding electron emission properties to the
      presence of finite BN ribbons located at the surface of the nanospheres
      (exhibiting zigzag edges), which behave like metals as confirmed by first
      principles calculations. In addition, our ab initio theoretical results indicate
      that the work function associated to these zigzag BN ribbons is 1.3 eV lower when
      compared with BN-bulk material.

PMID- 18333622
TI  - One-Step Nanoscale Assembly of Complex Structures via Harnessing of an Elastic
      Instability.
AB  - We report on a simple yet robust method to produce orientationally modulated two
      dimensional patterns with sub-100 nm features over cm2 regions via a solvent
      induced swelling instability of an elastomeric film with micrometer-scale
      perforations. The dramatic reduction of feature size ( approximately 10 times) is
      achieved in a single step, and the process is reversible and repeatable without
      the requirement of delicate surface preparation or chemistry. By suspending
      ferrous and other functional nanoparticles in the solvent, we have faithfully
      printed the emergent patterns onto flat and curved substrates. We model this
      elastic instability in terms of elastically interacting "dislocation dipoles" and
      find complete agreement between the theoretical ground-state and the observed
      pattern. Our understanding allows us to manipulate the structural details of the
      membrane to tailor the elastic distortions and generate a variety of
      nanostructures.

PMID- 18333623
TI  - Carbon nanotube-polymer nanocomposite infrared sensor.
AB  - The infrared photoresponse in the electrical conductivity of single-walled carbon
      nanotubes (SWNTs) is dramatically enhanced by embedding SWNTs in an electrically
      and thermally insulating polymer matrix. The conductivity change in a 5 wt % SWNT
      polycarbonate nanocomposite is significant (4.26%) and sharp upon infrared
      illumination in the air at room temperature. While the thermal effect
      predominates in the infrared photoresponse of a pure SWNT film, the photoeffect
      predominates in the infrared photoresponse of SWNT-polycarbonate nanocomposites.

PMID- 18333625
TI  - At-line quantitative ion mobility spectrometry for direct analysis of swabs for
      pharmaceutical manufacturing equipment cleaning verification.
AB  - The potential for ion mobility spectrometry (IMS) to provide rapid at-line
      quantitation of residues on surfaces via direct analysis of swabs is attractive
      for pharmaceutical manufacturing equipment cleaning verification. In this study,
      the development of an IMS method to provide acceptable quantitation of active
      pharmaceutical ingredients and cleaning agents is described. Key modifications to
      commercially available instrumentation were made to achieve a dynamic range of 5
      100 microg per 25 cm2 surface area and acceptable analyte recovery in the
      presence of ionizable matrix components. The results of this study effectively
      demonstrate the capability of IMS to serve as an at-line quantitative analytical
      method.

PMID- 18333624
TI  - Preparation, characterization and refolding in vitro of a recombinant human
      cyclophilin A mutant: effect of a single Pro/Ser substitution on cyclophilin A
      structure and properties.
AB  - A recombinant cyclophilin A (CypA) mutant, which carries a serine instead of
      proline at sequence 16, was prepared for structural and functional assessment for
      human CypA. Soluble expression of the recombinant CypA mutant in E. coli was
      obtained under 30 degrees C, 180 rpm culture condition after being induced by
      IPTG. Ion exchange chromatography was used to purify the CypA mutant in a single
      step, and a high activity recovery of target protein with a high purity was
      achieved. Peptide fragments produced by trypsin proteolysis were applied to MALDI
      TOF-MS, and searching results from the NCBI protein databank confirmed the
      protein attribution as well as the mutation sequence. Peptidyl-prolyl cis-trans
      isomerase activity was assayed for the CypA mutant using tetrapeptide substrate
      Suc-Ala-Ala-Pro-Phe-p-nitroanilide, and the calculated kcat/Km value was 1.5 x
      106 M-1 s-1 at 10 degrees C, which was 10-fold lower than the previously reported
      constant for wild-type CypA. An Eyring plot was also carried out. Inhibition by
      cyclosporine A demonstrated that the IC50 value was 26.5 nM. Meanwhile the
      expected enhancement of intrinsic tryptophan fluorescence was quenched by the
      mutation. The effect of CypA mutant on accelerating protein refolding in vitro
      was investigated in ribonuclease A refolding process, and it was found that 10%
      slow phase could be catalyzed by CypA. The protein was subject to urea and GdmCl
      denaturation, where both activity and fluorescence served as structural probes.
      Activity recovery indicated this CypA mutant was extremely sensitive to GdmCl and
      the susceptibility to urea was increased. Low pH could also destabilize CypA.
      Furthermore the refolding of this CypA mutant itself was studied. Although the
      activity yield was nearly unchanged, the former proposed folding/assembly pathway
      might be altered. Fluorescence chart also demonstrated that the folding time was
      extended, and fast-folding and slow-folding analysis indicated the slow-folding
      rate constant presented a concentration dependence property denoting the
      autocatalysis of the foldase.

PMID- 18333626
TI  - Organic-inorganic hybrid silica monolith based immobilized trypsin reactor with
      high enzymatic activity.
AB  - A novel kind of immobilized trypsin reactor based on organic-inorganic hybrid
      silica monoliths has been developed. With the presence of cetyltrimethyl ammonium
      bromide (CTAB) in the polymerization mixture, the hybrid silica monolithic
      support was prepared in a 100 microm i.d. capillary by the sol-gel method with
      tetraethoxysilane (TEOS) and 3-aminopropyltriethoxysilane (APTES) as precursors.
      Subsequently, the monolith was activated by glutaraldehyde, and trypsin was
      covalently immobilized. By monitoring the reaction of a decapeptide, C-myc
      (EQKLISEEDL), the enzymatic activity of the immobilized trypsin was calculated,
      and the results showed that the digestion speed was about 6600 times faster than
      that performed in free solution. The performance of such a microreactor was
      further demonstrated by digesting myoglobin, with the digested products analyzed
      by microflow reversed-phase liquid chromatography coupled with tandem mass
      spectrometry (microRPLC-MS/MS). With a stringent threshold for the unambiguous
      identification of the digests, the yielding sequence coverage for on-column
      digestion was 92%, the same as that obtained by in-solution digestion, whereas
      the residence time of myoglobin in the former case was only 30 s, about 1/1440 of
      that performed in the latter case (12 h). Moreover, such an immobilized trypsin
      reactor was also successfully applied to the digestion of a mixture of model
      proteins and proteins extracted from E. coli.

PMID- 18333628
TI  - Linking research and practice: evidence-based HIV prevention.

PMID- 18333627
TI  - Low-cost printing of poly(dimethylsiloxane) barriers to define microchannels in
      paper.
AB  - This paper describes the use of a modified x,y-plotter to generate hydrophilic
      channels by printing a solution of hydrophobic polymer (pol(dimethylsiloxane;
      PDMS) dissolved in hexanes onto filter paper. The PDMS penetrates the depth of
      the paper and forms a hydrophobic wall that aqueous solutions cannot cross. The
      minimum size of printed features is approximately 1 mm; this resolution is
      adequate for the rapid prototyping of hand-held, visually read, diagnostic assays
      (and other microfluidic systems) based on paper. After curing the printed PDMS,
      the paper-based devices can be bent or folded to generate three-dimensional
      systems of channels. Capillary action pulls aqueous samples into the paper
      channels. Colorimetric assays for the presence of glucose and protein are
      demonstrated in the printed devices; spots of Bromothymol Blue distinguished
      samples with slightly basic pH (8.0) from samples with slightly acidic pH (6.5).
      The work also describes using printed devices that can be loaded using
      multipipets and printed flexible, foldable channels in paper over areas larger
      than 100 cm2.

PMID- 18333629
TI  - Adapting evidence-based HIV prevention interventions.

PMID- 18333630
TI  - Circumcision as HIV prevention.

PMID- 18333631
TI  - Circumcision and HIV: implications for developed countries.

PMID- 18333632
TI  - Sex, Crimes, and HIV.

PMID- 18333633
TI  - Editorial: crime drama.

PMID- 18333634
TI  - Tarasoff and HIV: some considerations for therapists.

PMID- 18333635
TI  - HIV in the Georgia State Prison System.

PMID- 18333636
TI  - Editorial: no escape.

PMID- 18333637
TI  - Prison, re-entry, and HIV prevention.

PMID- 18333638
TI  - Assisting healthy HIV-positive parenthood.

PMID- 18333639
TI  - How I became an HIV-positive gay dad.

PMID- 18333640
TI  - Myoplasty for congenital macrostomia.
AB  - OBJECTIVE: To describe the different myoplasty techniques that could be used for
      limited commissural reconstruction. METHODS: Twelve cases of congenital
      macrostomia are reported, with different cleft lengths and termination sites. For
      each case, an orbicular myoplasty was performed, and in the case of extension to
      the area of the tragus or tonsillar pillars, a masseteric myoplasty or
      pharyngoplasty was performed. Functional and aesthetic results were analyzed.
      RESULTS: Functional results were excellent, with normal phonation, facial
      expression, and deglutition in the case of posterior extension. Aesthetic results
      were good, with only two cases of skin fasciculation during facial movement.
      CONCLUSIONS: Myoplasty in macrostomia could be limited to an orbicular
      reorientation in the case of a short cleft or can include a masseteric myoplasty
      or pharnygoplasty should the cleft extend further. Analyzing 90 reported cases of
      congenital macrostomia in the world literature, an important point has emerged.
      In some cases, the cleft could continue sagittally to the tonsillar pillars or
      laterally, distal to the anterior border of the masseter, to the region of the
      tragus. Repair in these cases requires reconstruction of the tonsillar pillars
      and masseteric repair in addition to orbicular removal. No reports in the world
      literature have referred to these other myoplasties that could be necessary, even
      if such pathology is very rare. In addition, no classification of congenital
      macrostomia was found in the world literature. We therefore propose a surgical
      classification of macrostomia relative to the nature of myoplasty required.

PMID- 18333641
TI  - Severe exercise-associated hyponatremia on the Kokoda Trail, Papua New Guinea.
AB  - Exercise-associated hyponatremia is the most common medical complication of
      ultradistance exercise and is usually caused by excessive hypotonic fluid intake.
      We report a case of severe hyponatremia in a healthy male trekking the Kokoda
      Trail in the remote Southern Highlands of Papua New Guinea. A 43-year-old male
      collapsed and had a generalized seizure in the afternoon of the third day of a
      guided trek. He was evacuated the following morning and was found to have a serum
      sodium level of 107 mmol/L on arrival to hospital. The case highlights that a
      high index of suspicion is required to identify patients with exercise-associated
      hyponatremia. Early diagnosis and appropriate management is critical to avoid the
      potentially fatal consequences of severe hyponatremia. The diagnosis and
      treatment of exercise-associated hyponatremia is particularly challenging in the
      remote Papua New Guinea jungle. Education of trek leaders, medics, and trekkers
      in appropriate preventative measures and the rapid treatment of exercise
      associated hyponatremia is essential to avoid recurrences of this life
      threatening condition.

PMID- 18333642
TI  - Factors affecting articulation skills in children with velocardiofacial syndrome
      and children with cleft palate or velopharyngeal dysfunction: a preliminary
      report.
AB  - OBJECTIVE: To examine the influence of speech perception, cognition, and implicit
      phonological learning on articulation skills of children with velocardiofacial
      syndrome (VCFS) and children with cleft palate or velopharyngeal dysfunction
      (VPD). DESIGN: Cross-sectional group experimental design. PARTICIPANTS: Eight
      children with VCFS and five children with nonsyndromic cleft palate or VPD.
      METHODS AND MEASURES: All children participated in a phonetic inventory task,
      speech perception task, implicit priming nonword repetition task, conversational
      sample, nonverbal intelligence test, and hearing screening. Speech tasks were
      scored for percentage of phonemes correctly produced. Group differences and
      relations among measures were examined using nonparametric statistics. RESULTS:
      Children in the VCFS group demonstrated significantly poorer articulation skills
      and lower standard scores of nonverbal intelligence compared with the children
      with cleft palate or VPD. There were no significant group differences in speech
      perception skills. For the implicit priming task, both groups of children were
      more accurate in producing primed nonwords than unprimed nonwords. Nonverbal
      intelligence and severity of velopharyngeal inadequacy for speech were correlated
      with articulation skills. CONCLUSIONS: In this study, children with VCFS had
      poorer articulation skills compared with children with cleft palate or VPD.
      Articulation difficulties seen in the children with VCFS did not appear to be
      associated with speech perception skills or the ability to learn new phonological
      representations. Future research should continue to examine relationships between
      articulation, cognition, and velopharyngeal dysfunction in a larger sample of
      children with cleft palate and VCFS.

PMID- 18333643
TI  - Birth prevalence of cleft lip and palate in Northern Ireland (1981 to 2000).
AB  - OBJECTIVE: The prevalence of cleft lip and/or palate (CL/P) in Northern Ireland
      (NI) was last reported for 1980 through 1990. This study was undertaken to update
      the prevalence of CL/P in NI for the 20-year period 1981 to 2000, to determine
      the pattern of prevalence, and to report the proportion of different cleft types
      and sex distribution. DESIGN: Retrospective, population-based analysis.
      PATIENTS/PARTICIPANTS: All live born children with CL/P in NI from 1981 to 2000
      were included. A total of 750 cases were identified. Resident births outside NI,
      stillbirths, abortuses, and children born with atypical orofacial clefts were
      excluded. Those with syndromes and submucous clefts were included in the study.
      RESULTS: The overall prevalence of children born with CL/P within NI for the
      period 1981 to 2000 was 1.47 per 1000 live births, or 1:682. This was consistent
      with the findings reported by other U.K. studies. There were no significant
      changes in the prevalence rates over any 5-year period. No significant
      seasonality trends were noted. Clefts of the palate only were always in the
      majority. More boys than girls were affected by cleft lip with or without cleft
      palate. There was a significant left-sided predilection for unilateral clefting
      of the lip. CONCLUSIONS: There have been no significant changes in the birth
      prevalence of children born with CL/P or the distribution or laterality of cleft
      type in the NI population during the past 20 years.

PMID- 18333644
TI  - Abnormal maxillary trapezoid pattern in human fetal cleft lip and palate.
AB  - OBJECTIVE: To elucidate abnormal growth patterns of human fetal maxillae with
      cleft lip and palate (CLP). SUBJECT: A total of 71 fetal maxillae with CLP were
      obtained from aborted human fetuses. METHOD: Dimensions of the maxillary
      trapezoid (MT), formed by the maxillary primary growth centers (MxPGC), were
      taken from radiographic images. The CLP dimensions were compared with maxillary
      trapezoid dimensions of normal fetuses from a previous study (Lee et al., 1992).
      MAIN OUTCOME MEASURES: Cleft lip subjects without a cleft palate, unilateral
      cleft lip-alveolar cleft or cleft palate (UCL+A/UCLP), and bilateral cleft lip
      alveolar cleft or cleft palate (BCL+A/BCLP) displayed abnormal MT patterns. MT
      abnormalities were most marked in the BCL+A/BCLP cohort. RESULTS: The MT growth
      of prenatal CLP maxillae was severely arrested, resulting in abnormal MT shape on
      palatal radiograms. BCL+A/BCLP subjects had a more protruded nasal septum than
      subjects with other types of CLPs, while UCL+A/UCLP subjects showed severe
      deviation of the protruded nasal septum toward the noncleft side. Cleft lip-only
      subjects also exhibited abnormal MT growth. CONCLUSION: MT is primarily involved
      in CLPs, so that the MT shape could be utilized as a sensitive indicator for the
      analysis of maxillary malformation in different types of CLPs.

PMID- 18333645
TI  - Hearing thresholds in newborns with a cleft palate assessed by auditory brain
      stem response.
AB  - OBJECTIVE: To objectively estimate the extent of hearing loss in infants with
      cleft palate and to measure the incidence of hearing loss. DESIGN: Retrospective
      consecutive case note review. SETTING: Tertiary institutional regional referral
      center for cleft lip and palate. PATIENTS, PARTICIPANTS: Consecutive cases of 90
      infants with cleft palate who underwent auditory brain stem response (ABR)
      threshold estimation. INTERVENTIONS: ABR threshold estimation during natural
      sleep in infants with cleft palate under 2 months of age. MAIN OUTCOME MEASURES:
      Hearing level thresholds as estimated by auditory brain stem response and
      categorized as normal (< 25 < or = 35 dB nHL) , mild (> 35 < or = 45 dB nHL),
      moderate (> 45 < or = 65 dB nHL), severe (> 65 < or = 90 dB nHL), and profound (>
      90 dB nHL) hearing loss. RESULTS: Hearing loss was present in 82% of the infants
      tested. Most of the hearing loss was conductive (89%), mild (86%), and bilateral
      (84%). Average age of ABR threshold estimation was 48.5 days. In 22% of infants
      there was an associated syndrome. The mean air conduction thresholds for the
      right and left ear were 40 and 39.7, respectively. CONCLUSION: The incidence of
      hearing loss in a cohort of cleft palate infants has been objectively estimated
      by auditory brain stem response thresholds and was found to be very high (82%).

PMID- 18333646
TI  - Effect of cleft palate repair on the susceptibility to contraction-induced injury
      of single permeabilized muscle fibers from congenitally-clefted goat palates.
AB  - OBJECTIVE: Despite cleft palate repair, velopharyngeal competence is not achieved
      in approximately 15% of patients, often necessitating secondary surgical
      correction. Velopharyngeal competence postrepair may require the conversion of
      levator veli palatini muscle fibers from injury-susceptible type 2 fibers to
      injury-resistant type 1 fibers. As an initial step to determining the validity of
      this theory, we tested the hypothesis that, in most cases, repair induces the
      transformation to type 1 fibers, thus diminishing susceptibility to injury.
      INTERVENTIONS: Single permeabilized levator veli palatini muscle fibers were
      obtained from normal palates and nonrepaired congenitally-clefted palates of
      young (2 months old) and adult (14 to 15 months old) goats and from repaired
      palates of adult goats (8 months old). Repair was done at 2 months of age using a
      modified von Langenbeck technique. MAIN OUTCOME MEASURES: Fiber type was
      determined by contractile properties and susceptibility to injury was assessed by
      force deficit, the decrease in maximum force following a lengthening contraction
      protocol expressed as a percentage of initial force. RESULTS: For normal palates
      and cleft palates of young goats, the majority of the fibers were type 2 with
      force deficits of approximately 40%. Following repair, 80% of the fibers were
      type 1 with force deficits of 20% +/- 2%; these deficits were 45% of those for
      nonrepaired cleft palates of adult goats (p < .0001). CONCLUSION: The decrease in
      the percentage of type 2 fibers and susceptibility to injury may be important for
      the development of a functional levator veli palatini muscle postrepair.

PMID- 18333647
TI  - Subglossopalatal synechia in association with cardiac and digital anomalies.
AB  - A 1-day-old boy in respiratory distress had a midline soft tissue band between
      the floor of the mouth and the posterior edge of the hard palate. There was also
      a soft palatal cleft, cardiac anomalies, and a hypoplastic right fifth finger and
      toe. Although his airway initially improved following urgent excision of the
      subglossopalatal band, he continued to have episodic desaturations. A tongue-lip
      adhesion opened his airway, and he subsequently underwent resection of
      juxtaductal aortic coarctation and ligation of patent ductus arteriosus and left
      superior vena cava. Congenital oral synechiae are uncommon. Affected infants
      often require prompt intervention secondary to respiratory distress and feeding
      difficulty. Review of the literature indicates that midline subglossopalatal
      synechia with cardiac and digital anomalies may be in the oromandibular-limb
      hypogenesis spectrum.

PMID- 18333648
TI  - The structural implications of a unilateral facial skeletal cleft: a three
      dimensional finite element model approach.
AB  - OBJECTIVE: For children born with a unilateral facial skeletal cleft, oral motor
      function is impaired and skeletal development and growth are asymmetrical with
      regard to the midsagittal plane. This study was designed to verify that a
      unilateral skeletal cleft and its dimensions (i.e., depth and width) affect the
      severity of the asymmetric stress and strain distribution within the maxilla.
      METHODS: A three-dimensional finite element model of a normal maxilla was
      developed from pediatric, subject-specific computerized tomography scan data. A
      clefting pattern then was introduced to simulate varying degrees of deformity in
      geometry, with the bone properties and boundary conditions held constant. The
      asymmetric index was introduced to quantify the asymmetrical stress and strain
      distribution within the maxilla with regard to the midsagittal plane. RESULTS:
      The unilateral skeletal cleft led to a nonuniform, asymmetric stress and strain
      distribution within the maxilla: intensified on the noncleft side and weakened on
      the cleft side. As the depth of the unilateral cleft increased, the stress and
      strain distribution became increasingly asymmetric as measured by the asymmetric
      index. In contrast, the width of the cleft had minimal effect on the asymmetrical
      stress and strain distribution. INTERPRETATION/CONCLUSION: These results implied
      that a child born with a unilateral cleft would be expected to have an asymmetric
      skeletal development between the noncleft and the cleft sides as a consequence of
      an asymmetric functional loading pattern.

PMID- 18333649
TI  - A population-based evaluation of antenatal diagnosis of orofacial clefts.
AB  - OBJECTIVES: To evaluate the changes in prevalence and antenatal detection of
      cleft lip with or without cleft palate and isolated cleft palate and to describe
      the association between anomalies and rates of antenatal diagnosis in Nova Scotia
      from 1992 to 2002. DESIGN: This population-based cohort study employed the Nova
      Scotia Atlee Perinatal Database, the Fetal Anomaly Database, and IWK Cleft Palate
      Database in Halifax, Nova Scotia, Canada. OUTCOME MEASURES: Cleft type, mode of
      diagnosis, and associated abnormalities of orofacial clefts for liveborn infants,
      stillbirths, and second trimester terminations of pregnancy between 1992 and 2002
      were determined. RESULTS: There were 225 fetuses identified as having orofacial
      clefts. The overall prevalence of clefts was 2.1 in 1000 live births, and this
      prevalence did not change with time. The overall antenatal detection of cleft lip
      with or without cleft palate was 23%; however, there was improvement in detection
      of cleft lip with or without cleft palate from the years 1992 to 1996 (14%) to
      the years 1997 to 2002 (30%, p = .02). No isolated cleft palates were detected
      antenatally. Associated structural anomalies were seen in 34.2% of cases with
      orofacial clefts, and chromosomal abnormalities were associated with 9.8%.
      CONCLUSIONS: The prevalence of orofacial clefts in Nova Scotia has not changed
      from 1992 to 2002. The proportion of antenatally diagnosed cleft lip with or
      without cleft palate in Nova Scotia is consistent with rates reported in the
      literature and has increased from 1992 to 2002.

PMID- 18333650
TI  - Incidence of oronasal fistulae and velopharyngeal insufficiency after cleft
      palate repair: an audit of 211 children born between 1990 and 2004.
AB  - OBJECTIVE: We present an audit of primary cleft palate surgery at our unit,
      including rates of oronasal fistula development, speech outcomes, and rates of
      velopharyngeal insufficiency requiring secondary surgery. DESIGN: A retrospective
      study of patients with all cleft palate types, born between January 1990 and
      December 2004, who underwent primary palatoplasty at Middlemore Hospital,
      Auckland, New Zealand. PATIENTS: The study included 211 patients, collectively
      operated on by five different surgeons. RESULTS: The overall rate of true fistula
      development was 12.8% over a mean follow-up period of 4 years 10 months. The
      incidence of true fistulae that required surgical repair was 8.1%. Fistula rates
      were higher for more severe degrees of clefting but were not affected by gender
      or type of surgical repair. Overall, 31.8% of the study population had some
      degree of hypernasality following primary palatoplasty. Secondary surgery for
      velopharyngeal insufficiency was required in 13.3% of patients. Following
      surgical correction of velopharyngeal insufficiency, no patients were reported to
      have appreciable hypernasality and 21.7% were reported to have mild
      hypernasality, a result comparable to previously published audits. The
      requirement for secondary surgery was higher in patients with more severe clefts.
      CONCLUSION: Our results are comparable to other recent studies. We believe that
      highly coordinated cleft care helps ensure such outcomes. These data provide a
      benchmark against which we can measure future performance in our attempts to
      improve outcomes of cleft repair.

PMID- 18333651
TI  - Prevalence of abnormalities in dental structure, position, and eruption pattern
      in a population of unilateral and bilateral cleft lip and palate patients.
AB  - OBJECTIVE: To evaluate the dental characteristics of patients subjected to a
      protocol that included early secondary gingivoalveoloplasty (ESGAP). DESIGN:
      Panoramic radiographs of 87 patients with unilateral cleft lip and palate (UCLP)
      and 29 with bilateral cleft lip and palate (BCLP) were evaluated. Missing and
      supernumerary teeth were also quantified on the cleft and noncleft side and in
      the maxilla and mandible. Crown and root malformations and tooth rotations were
      quantified. A subsample in permanent dentition was extrapolated to analyze canine
      eruption patterns. RESULTS: A total of 48.8% of the UCLP patients presented with
      missing permanent lateral incisors in the cleft area and 6.1% contralaterally. A
      total of 4.9% presented with missing second maxillary premolars on the cleft site
      and 1.2% contralaterally. A total of 7.3% presented with supernumerary lateral
      incisors, and 45% of the BCLP cleft sites presented with missing lateral
      incisors, while 25% of the cleft sites presented second maxillary premolars
      agenesis. Five percent of the cleft sites presented with supernumerary lateral
      incisors. Evaluation of the subsample in permanent dentition showed that 15.5%
      had a canine retention and 4.4% of the canines had to be surgically exposed. A
      significant association was observed between canine inclination and retention but
      not with absence of the lateral incisor. CONCLUSIONS: The frequency of dental
      anomalies in this sample was similar to other cleft populations. As surgical
      trauma has been suggested to damage forming teeth, the results of this study
      indicated that ESGAP has no detrimental influence on subsequent dental
      development.

PMID- 18333652
TI  - Characteristics of 2733 cases diagnosed with deformational plagiocephaly and
      changes in risk factors over time.
AB  - OBJECTIVES: To describe infant and maternal characteristics among infants with
      plagiocephaly and to quantify time trends in potential risk factors for
      plagiocephaly. DESIGN: Case-only study. We described the characteristics of
      individuals born between 1987 and 2002. We also compared characteristics of
      individuals born from 1987 through 1990, before the American Academy of
      Pediatrics 1992 sleep-position recommendations, with those of individuals born
      from 1991 to 2002. SETTING: Children's Craniofacial Center at Children's Hospital
      and Regional Medical Center in Seattle, Washington. PARTICIPANTS: Subjects
      included 2733 infants diagnosed with deformational plagiocephaly or brachycephaly
      before 18 months of age who were born from 1987 to 2002. MAIN OUTCOME MEASURE:
      Descriptive statistics, odds ratios, and 95% confidence intervals. RESULTS: Among
      individuals born from 1991 to 2002, 91.6% had occipital-only flattening, 17.2%
      were brachycephalic, 67.7% were boys, and 9.9% were multiple birth infants. As
      compared with individuals born from 1987 through 1990, those born from 1991 to
      2002 were more apt to be a multiple birth (odds ratio [OR] 3.4, 95% confidence
      interval [CI]: 0.8, 14.1) and to have a mother > or =35 years of age (OR, 3.2;
      95% CI, 1.4 to 7.3); they were hospitalized less commonly at birth for 4 or more
      days (OR, 0.02; 95% CI, 0.01 to 0.06). CONCLUSIONS: Several risk factors for
      plagiocephaly were more common among individuals born after the 1992 American
      Academy of Pediatrics sleep-position recommendations. These results are
      consistent with the explanation that supine sleeping modifies the association
      between such risk factors and plagiocephaly. Further studies with a control group
      are needed to validate this conclusion.

PMID- 18333653
TI  - Caregiver and patient reported outcomes after repair of cleft lip and/or palate
      in the Philippines.
AB  - OBJECTIVES: To establish the feasibility of conducting outcomes research among
      patients treated during a medical mission and to identify the salient outcomes
      for patients and caregivers in one region of the Philippines. DESIGN AND SETTING:
      Prospective structured interview conducted in or near participants' homes on the
      island of Cebu, Philippines. PARTICIPANTS: Individuals who had surgery at least 6
      months earlier within the study region were eligible. Recipients of surgery were
      located from surgical records and by word of mouth. MAIN OUTCOME MEASURES: (1)
      Proportion of individuals located. (2) Primary outcomes of oral cleft repair
      identified for the sample. RESULTS: Of 99 people on a surgical list, 52 (53%)
      were located, eight were excluded (ineligible, unavailable, or inaccessible), and
      44 agreed to participate in the study. Ten participants were identified via word
      of mouth. Seventy-five interviews were conducted (21 caregiver-patient pairs, one
      adolescent, and 32 caregivers of a child <7 years). Nearly all participants (99%)
      would encourage others to pursue surgery. Open-ended questions were coded to
      identify primary outcomes: improved speech (52%), improved eating (25%), social
      benefits (14%), and improved appearance (6%). Caregivers (50%) and patients (68%)
      reported that improved speech was the most important change after surgery.
      CONCLUSIONS: Patients and caregivers ascribe positive changes related to cleft
      surgery. Outcomes research requires cooperation with local professionals who can
      communicate effectively. These data serve to demonstrate feasibility and as a
      model for future studies of treatment outcomes in follow-up to international
      medical missions.

PMID- 18333654
TI  - Tick attachment sites.
AB  - OBJECTIVE: The duration of tick attachment is related to the likelihood of
      disease transmission. To be able to locate and remove an attached tick is
      important. METHODS: Sixty-seven patients presenting with tick bites to the
      Karadeniz Technical University emergency department and 3 different first-stage
      health institutions between April and July 2006 were investigated to determine
      the distribution of the bites. RESULTS: Tick attachment site distribution was
      determined as follows: 9% head-neck, 5% arm, 24% stomach-groin, 7% back, 18%
      chest-shoulder, 25% leg-foot, and 12% hip. CONCLUSIONS: According to the results
      of our study, 20% of ticks attach to regions of the body that patients cannot
      themselves see. After travel in endemic areas, a complete inspection of the
      entire body surface is required to achive early tick removal.

PMID- 18333655
TI  - Adaptation to high altitude in Sherpas: association with the insertion/deletion
      polymorphism in the Angiotensin-converting enzyme gene.
AB  - OBJECTIVE: Sherpas are well-known for their physical strength at high altitudes.
      They adapt to high altitude so well that little acute or chronic mountain
      sickness has been documented in them. The possible genetic basis for this
      adaptation is, however, unclear. The objective of this study was to elucidate the
      genetic background underlying this characteristic among Sherpas with respect to
      the angiotension-converting enzyme (ACE) gene. METHODS: We enrolled 105 Sherpa
      volunteers in Namche Bazaar (3440 meters) and 111 non-Sherpa Nepalese volunteers
      in Kathmandu Valley (1330 meters) in Nepal. Information about high-altitude
      exposure and physiological phenotypes was obtained via fieldwork investigation.
      The genotype of the insertion/deletion (I/D) polymorphism in the ACE gene was
      identified by polymerase chain reaction. Serum ACE activity was also measured.
      RESULTS: The distribution of the I dominant genotype (II & ID) and the I allelic
      frequency were significantly more prevalent in Sherpas (II & ID: 94.3%, I allele:
      73.3%) than in non-Sherpas (II & ID: 85.6%, P = .035; I allele: 64.0%, P = .036).
      Moreover, despite residing at high altitude, the circulating ACE levels of
      Sherpas were statistically similar to those of non-Sherpas at low altitudes
      (Sherpas: 14.5 +/- 0.4 IU/L/37 degrees C; non-Sherpas: 14.7 +/- 0.4 IU/L/37
      degrees C; P = .755). CONCLUSIONS: These findings suggest that the
      overrepresented I allele of the ACE gene in Sherpas might be one of the
      fundamental genetic factors responsible for maintaining physiological low
      altitude ACE activity at high altitude, which may have an advantageous
      physiological role in adapting to a high-altitude environment.

PMID- 18333657
TI  - Virus removal from water by a portable water treatment device.
AB  - OBJECTIVE: Few portable point-of-use (POU) devices are available for treatment of
      water by recreational enthusiasts who may obtain water from untreated sources
      (rivers, lakes, etc.). This study evaluated a POU device containing a structure
      matrix capable of removing viruses from water without the use of a disinfectant.
      METHODS: The unit was evaluated for the removal of poliovirus type 1, rotavirus
      SA-11, human norovirus, and a wide range of different coliphages exhibiting
      different isoelectric points, sizes, and shapes. RESULTS: The removal of all
      virus types tested exceeded 99.99%. CONCLUSION: The tested unit complied with the
      criteria guidelines for virus removal under the US Environmental Protection
      Agency's "Guide Standard and Protocol for Testing of Microbiological Water
      Purifiers."

PMID- 18333658
TI  - Temperature and blood pressure following amlodipine overdose.
AB  - The cardiovascular system participates in both blood pressure (BP) and
      temperature regulation. As a result, salt ingestion creates conflict between BP
      and temperature homeostasis, as vasodilatation that would promptly lower the BP
      would simultaneously increase cutaneous blood flow, thereby accelerating heat
      loss. If temperature homeostasis has precedence over blood pressure homeostasis,
      as postulated by the thermoregulatory-vascular remodeling (TVR) hypothesis, then
      in order to minimize heat loss, BP remains elevated following salt ingestion
      until the kidneys excrete the excess salt. A case of amlodipine overdose offered
      an opportunity to test a corollary of the TVR hypothesis: vasodilators should
      cause a drop in body temperature and/or an increase in the metabolic rate.
      Following the ingestion of 1000 mg of amlodipine, the temperature and BP of a
      single patient were monitored during the initial 36 hours and during the 13th day
      of hospitalization. The BP dropped markedly between the fifth and seventh hours
      postingestion, but then rose steadily and normalized by 28 hours postingestion.
      The temperature was normal at 7 hours postingestion, declined gradually between
      the seventh and 26th hours postingestion, stabilized between the 26th and 31st
      hours postingestion, then began to rise. During this case of amlodipine overdose,
      a modest temperature decline lagged behind a marked BP decline. As the BP rose,
      the temperature also rose, but lagged behind the BP increases. These findings
      suggest that there is a relationship between BP and temperature and are
      consistent with the TVR hypothesis.

PMID- 18333659
TI  - Unburying the facts about avalanche victim pathophysiology.

PMID- 18333660
TI  - Searches past 100 hours successful in Oregon in 2006.

PMID- 18333661
TI  - When searches become futile.

PMID- 18333663
TI  - Mood, illness and injury responses and recovery with adventure racing.
AB  - OBJECTIVE: Exercise stress, immune status, and mood are interrelated. The stress
      of adventure racing is unique; exercise is very prolonged and competitive, with
      severe sleep deprivation and sustained cognitive demands, usually in arduous
      terrain and environmental conditions. The purpose of this prospective,
      descriptive study was to identify mood changes along with symptoms of illness and
      injury during and in the weeks following an international-level adventure race.
      METHODS: Mood, sleep, injury, and illness data were collected using
      questionnaires before, during, and for 2 weeks following New Zealand's Southern
      Traverse Adventure Race in November 2003. RESULTS: Mood was variable between
      athletes, but peaks of altered mood subscores were evident (P < .05) during the
      first 24 hours of racing, around race completion, and, as was hypothesized, 3
      days after racing. Altered mood subscores resolved within 2 weeks. Symptoms of
      upper respiratory illness were most common immediately before (25/60, 42%) and
      after (28/49, 57%) racing, and largely resolved over the 2-week follow-up (5/27,
      19%). Skin wounds and infections were common (43/49, 88%) immediately after the
      race but settled quickly. Pain was universal (100%), and musculoskeletal injury
      was common (38/48, 79%). Gastrointestinal complaints were common at the finish
      (8/49, 16%) and during the next 5 days but settled more quickly than upper
      respiratory symptoms. CONCLUSIONS: Adventure racing of approximately 100 hours
      causes significant symptomatic injury and illness and mood state disruption,
      which generally resolve within a fortnight following racing. Disrupted mood and
      symptoms of illness and injury indicate athlete susceptibility to overreaching or
      overtraining without sufficient recovery.

PMID- 18333664
TI  - Carbon monoxide exposure on Denali: comparing the 2004 and 2005 climbing seasons.
AB  - OBJECTIVE: This study assessed a potential relationship between elevated
      carboxyhemoglobin (COHb) levels and the presence of acute mountain sickness (AMS)
      at 4300 m on Denali and evaluated the relationship between COHb levels, AMS, and
      climber characteristics and behaviors. Building on our research done in 2004, in
      this article we report further data gathered during the 2005 climbing season and
      evaluate the combined results. METHODS: Participants were screened for AMS using
      the Lake Louise Self-Report Questionnaire and answered questions focusing on AMS
      symptoms, AMS prevention, and previous history of altitude illness.
      Carboxyhemoglobin levels were measured by serum co-oximetry. Additional questions
      assessed stove practices, climbing practices, and climber behaviors.
      Nonparametric statistical analyses were performed to examine potential
      relationships between COHb levels, AMS symptoms, and climber behaviors across the
      2 years and with years combined. RESULTS: Overall, 317 climbers participated in
      the 2-year study. As in 2004, the combined data demonstrated no relationship
      between positive carbon monoxide (CO) exposure and positive criteria for AMS (P =
      .276). Climbers in 2005 were 1.92 times more likely to meet positive criteria for
      AMS, compared to climbers in 2004 (P = .028). On the contrary, climbers in 2004
      were 3.93 times more likely to be CO exposed than climbers in 2005 (P = .003).
      Overall, climbers descending the mountain were more likely to be positive for CO
      exposure (5.56 times more likely than ascending climbers, P = .002) and to have
      higher overall mean COHb levels (2.26% descending vs 0.93% ascending, P = .006).
      The previous association between increased stove use and climbers who met
      positive criteria for AMS was not observed in the 2005 or in the combined data (P
      = .715). A relationship was observed between increased hours of operating stoves
      and increased COHb levels (P = .002). Female climbers were 2.041 times more
      likely to meet criteria for AMS (P = .043). CONCLUSIONS: No relationship between
      AMS symptoms and CO exposure was observed. As found in our initial study,
      descending climbers had higher overall COHb levels and an increased risk of CO
      exposure (COHb of >3% in nonsmokers and >10% in smokers). Also, increased hours
      of stove operation was linked to climbers who had elevated COHb levels.

PMID- 18333665
TI  - Animal bites and stings reported by United States poison control centers, 2001
      2005.
AB  - OBJECTIVE: There is not a single data source for information on the extent of
      nonfatal injuries inflicted by animals. Although individuals bitten or stung by
      animals may not visit a health care provider, they may call poison control
      centers (PCCs) for information. These centers are one source of information on
      the frequency of occurrence of injuries from animals. METHODS: The American
      Association of Poison Control Centers compiles an annual report of exposure calls
      to various agents, including chemicals, medications, animal bites and stings,
      plants, and use of antivenoms from their network of PCCs. An estimate of the
      severity of exposure for each call is also determined. This review examines
      summary data on different species of animal bites and stings reported by PCCs
      from 2001 to 2005. RESULTS: From 2001 to 2005 there were 472 760 reports of
      animal bites and stings, an average of 94,552 per year. There was a trend noted
      for increasing use of antivenom over this period. Twenty-seven deaths were
      recorded, most from snakebites. CONCLUSIONS: Poison control centers are a source
      of information for health care workers on management of animal bites and stings.
      The database maintained by the American Association of Poison Control Centers is
      another source of information on the magnitude and public health impact of
      injuries from animals.

PMID- 18333667
TI  - Pioneer of the high realm: Michael Ward's life of medicine, mountaineering, and
      exploration.

PMID- 18333668
TI  - Development of the special skills post in expedition medicine for general
      practice registrars in Australia.
AB  - Wilderness, mountain, and expedition medicine training for physicians is now well
      developed in North America and Europe. This paper describes the development and
      content of the first such program in Australia. The Special Skills Post in
      Expedition Medicine is a 6-month post, developed by General Practice Training
      Tasmania, that is integrated into general practice training and combines clinical
      placements in travel medicine, general practice, emergency medicine, a self
      guided workbook covering core and elective topics, and an 8-day field trip.

PMID- 18333670
TI  - Three cases of mydriasis following consumption of mackerel fish.

PMID- 18333671
TI  - Bone-related effects of contaminants in seals may be associated with vitamin D
      and thyroid hormones.
AB  - The high levels of polychlorinated biphenyls (PCBs) and DDT in gray seal
      (Halichoerus grypus) and ringed seal (Phoca hispida botnica) in the Baltic Sea
      have been associated with pathological disruptions, including bone lesions and
      reproductive failures. The underlying environmental and toxicological mechanisms
      leading to these pathological changes are not yet fully understood. The present
      study investigated the relationship between the individual contaminant load and
      bone- and thyroid-related effects in adult gray seals (n=30) and ringed seals
      (n=46) in the highly contaminated Baltic Sea and in reference areas (Sable
      Island, Canada, and Svalbard, Norway). In the gray seals, multivariate and
      correlation analyses revealed a clear relationship between circulating 1,25
      dihydroxyvitamin D(3) (1,25(OH)(2)D), calcium, phosphate, and thyroid hormone
      (TH) levels and hepatic PCB and DDT load, which suggests contaminant-mediated
      disruption of the bone and thyroid homeostasis. Contaminants may depress
      1,25(OH)(2)D levels or lead to hyperthyroidism, which may cause bone resorption.
      In the ringed seals, associations between circulating 1,25(OH)(2)D, THs, and
      hepatic contaminants were less prominent. These results suggest that bone lesions
      observed in the Baltic gray seals may be associated with contaminant-mediated
      vitamin D and thyroid disruption.

PMID- 18333672
TI  - Mutagenic hazards of complex polycyclic aromatic hydrocarbon mixtures in
      contaminated soil.
AB  - The objective of the present study was to evaluate hazard/risk assessment methods
      for complex environmental mixtures that involve a targeted, priority chemical
      approach based on the cumulative hazard/risk of known mixture components or
      analyses of sufficiently similar mixtures. Ten polycyclic aromatic hydrocarbon
      (PAH)-contaminated soils were separated into nonpolar and semipolar fractions,
      and both fractions elicited positive responses on the Salmonella reverse mutation
      assay. Targeted and nontargeted methods of hazard prediction routinely
      overestimated mutagenic activities for the nonpolar soil fractions, suggesting
      nonadditive interactions of PAHs in complex mixtures. This suggests that current
      risk assessment methods for complex mixtures may provide conservative estimates
      regarding soils contaminated with priority PAHs alone. Significant
      underestimations of total risk, however, will be obtained if the soils also
      contain unidentified PAHs as well as polycyclic aromatic compounds and related
      compounds that contribute to the total mutagenic activity. Furthermore, estimates
      of excess lifetime cancer risk associated with the nondietary ingestion of the
      PAH-contaminated soils studied here indicate that a traditional risk assessment
      model based on identified priority PAHs and an assumption of additivity generally
      underestimates the risk associated with the nonpolar soil fractions (in
      comparison to bioassay-derived risk estimates). Additional cancer risk may be
      associated with the more polar compounds that also are found at these
      contaminated sites and that rarely are included in the standard risk assessment
      methodology.

PMID- 18333673
TI  - Effects of anaerobic incubation on the desorption of polycyclic aromatic
      hydrocarbons from contaminated soils.
AB  - Incubation of field-contaminated soil under anaerobic conditions can lead to
      increased mobilization of polycyclic aromatic hydrocarbons (PAHs) into water. In
      the present study, we evaluated the effects of anaerobic incubation on the rate
      and extent of desorption of PAH from two field-contaminated soil samples. One was
      a highly contaminated soil from a former wood-preserving site that had not been
      subject to previous treatment; the other was a soil from a former manufactured
      gas plant site that had been treated in an aerobic bioreactor. A two-site
      desorption model was applied to quantify the fast and slowly desorbing fractions
      of each PAH and the corresponding first-order rate constants for each fraction.
      For most of the PAHs, the total amount desorbed after 18 d from anaerobically
      incubated samples was significantly greater than that from their counterparts not
      subjected to anaerobic incubation, but the overall effect was modest. The rate
      constant corresponding to the slowly desorbing fraction (k(2)) was much higher
      for the samples incubated under active anaerobic conditions than that for the
      controls, implying anaerobic incubation had the greatest influence on the soil
      compartments controlling the slow release of PAHs. Anaerobic incubation had
      little to no effect on the rapidly desorbing fraction.

PMID- 18333674
TI  - Detecting the transport of toxic pesticides from golf courses into watersheds in
      the Precambrian Shield region of Ontario, Canada.
AB  - Golf courses impact the environment through alterations to habitat and through
      the release of nutrients and pesticides. The Precambrian Shield region of central
      Ontario, Canada, which is a major recreational area, is especially susceptible to
      the impacts of golf courses as a result of the geology and hydrology of the
      region. In a monitoring program at two golf courses in the Muskoka region
      conducted during the spring, summer, and fall of 2002, semipermeable membrane
      devices (SPMDs) were deployed into streams that drain the golf courses. The
      extracts from the SPMDs were tested for toxicity using bioassays with early life
      stages of an aquarium fish, the Japanese medaka (Oryzias latipes). Toxicity was
      assessed using a scoring system developed for the present study. The bioassays
      with medaka indicated that toxicity was highest in extracts from SPMDs deployed
      during the spring and the fall. The peaks in toxicity for the SPMDs deployed at
      the two golf courses corresponded with the presence in the SPMD extracts of
      pentachloronitrobenzene (PCNB) at concentrations up to 334 ng/SPMD. Quintozene is
      the turfgrass fungicide in which PCNB is the active ingredient.
      Pentachlorothioanisole, an anaerobic degradation product of PCNB, also was
      detected in the SPMDs deployed during the spring. Extracts prepared from SPMDs
      with high toxicity contained residues of a surfactant used in pesticide
      formulations, nonylphenol, at concentrations up to approximately 20 microg/SPMD.
      Overall, these data indicate that some pesticides applied to golf courses in the
      Precambrian Shield of central Ontario may have the potential to cause toxic
      impacts to aquatic organisms in adjacent watersheds.

PMID- 18333675
TI  - Mercury concentrations in blood and feathers of prebreeding Forster's terns in
      relation to space use of San Francisco Bay, California, USA, habitats.
AB  - We examined mercury concentrations and space use of prebreeding Forster's terns
      (Sterna forsteri) in San Francisco Bay, California, USA, to assess factors
      influencing mercury levels in piscivorous birds. In 2005 and 2006, we collected
      blood and feathers from 122 Forster's terns and radio-marked and tracked 72 terns
      to determine locations of dietary mercury uptake. Capture site and capture date
      were the most important factors explaining variation in blood mercury
      concentrations (geometric mean +/- standard error: 1.09+/-0.89 microg/g wet wt),
      followed by sex and year. Accordingly, radiotelemetry data revealed that
      Forster's terns generally remained near their site of capture and foraged in
      nearby salt ponds, managed and tidal marshes, and tidal flats. In contrast,
      capture site and capture date were not important factors explaining variation in
      feather mercury concentrations, probably because feathers were grown on their
      wintering grounds several months prior to our sampling. Instead, sex and year
      were the most important factors explaining mercury concentrations in breast
      feathers (9.57+/-8.23 microg/g fresh wt), and sex was the most important factor
      for head feathers (6.94+/-7.04 microg/g fresh wt). Overall, 13 and 22% of
      prebreeding Forster's terns were estimated to be at high risk for deleterious
      effects due to mercury concentrations in blood (>3.0 microg/g wet wt) and
      feathers (>20.0 microg/g fresh wt), respectively. Breeding terns are likely to be
      even more at risk because blood mercury concentrations more than tripled during
      the 45-d prebreeding time period. These data illustrate the importance of space
      use and tissue type in interpreting mercury concentrations in birds.

PMID- 18333676
TI  - Laboratory degradation studies of four endocrine disruptors in two environmental
      media.
AB  - We investigated the degradation of 17beta-estradiol (E(2)), 17alpha
      ethinylestradiol (EE(2)), bisphenol-A (BPA), and 4-n-nonylphenol (4-n-NP) in
      river water-sediment and groundwater-aquifer material under aerobic and anaerobic
      conditions. The results showed rapid degradation of all four compounds in both
      media with >90% of the four compounds degraded within the first 2 to 4 d under
      both conditions. However, degradation rates were extremely slow for the remaining
      period. Model derived 50% dissipation time (DT50) values in river water-sediment
      slurries ranged from 0.24 to 1.5 d (E(2)), 0.29 to 1.1 d (EE(2)), 1.2 to 1.4 d
      (BPA), and 0.42 d (4-n-NP), while the 90% dissipation time (DT90) values for the
      four endocrine-disrupting chemicals (EDCs) ranged from 0.9 to 2.8 d under both
      conditions. A minor difference was observed in DT50 and DT90 values for the four
      EDCs in groundwater- aquifer material under aerobic conditions as compared with
      river water-sediment. Under anaerobic conditions, DT90 values ranged from >1,000
      d (EE(2)) to >300 d (BPA), in groundwater-aquifer material. Degradation of the
      four compounds under anaerobic conditions was attributed to the sulfate-, nitrate
      , and iron-reducing conditions within the tested media; however, it was
      postulated that overall degradation of the compounds was also influenced by
      abiotic factors, accounting for nearly 6 to 40% (river water- sediment) and 0 to
      18% (groundwater-aquifer material) under the two conditions tested.

PMID- 18333677
TI  - Heterocypris incongruens as a tool to estimate sewage sludge toxicity.
AB  - The toxicity of 13 sewage sludges was evaluated in relation to the crustacean
      Heterocypris incongruens. The bioassay used was a commercial, direct contact test
      that allows evaluation of solid-phase toxicity. Evaluation of sewage sludges
      included physicochemical properties (pH, total organic C, total N, cation
      exchange capacity, total exchangeable bases, available forms of P and K, and
      electrical conductivity), heavy metal content (cadmium, chromium, copper, lead,
      nickel, and zinc), and content of polycyclic aromatic hydrocarbons (16 from the
      U.S. Environmental Protection Agency list). The evaluated parameters were then
      compared with bioassay results (mortality and growth inhibition). Sewage sludges
      were characterized by optimal physicochemical properties; low K (<5.64 mg/kg) and
      total organic C (177-253 g/kg) levels were noted. Contaminant content (heavy
      metals and polycyclic aromatic hydrocarbons) clearly differed between individual
      sewage sludges. Polycyclic aromatic hydrocarbon contents ranged from 3.8 to 36.4
      mg/kg. Total concentrations of heavy metals in all sewage sludges (with the
      exception of one sludge) were lower than the pollutant concentration limits for
      land application. Heterocypris incongruens mortality when sludge was applied at
      doses of 6, 12, or 24% ranged from 0 to 70%, from 4.7 to 72.1%, and from 0 to
      100%, respectively. Average growth inhibition was 39.7 to 46.6% (depending on the
      sludge dose applied). Any stimulating influence of two sewage sludges on the test
      organism was recorded. The median lethal concentrations calculated for individual
      sewage sludges ranged from 88 to 956 g sewage sludge/ kg.

PMID- 18333678
TI  - Modeling the influence of environmental heterogeneity on heavy metal exposure
      concentrations for terrestrial vertebrates in river floodplains.
AB  - To analyze the influence of environmental heterogeneity on heavy metal exposure
      concentrations for terrestrial vertebrates in river floodplains, a spatially
      explicit exposure model has been constructed (SpaCE-model: Spatially explicit
      cumulative exposure model). This model simulates the environmental use of
      individual organisms by selecting model cells to be foraged in within a
      multicelled, heterogeneous landscape. Exposure durations and exposure
      concentrations are calculated for the selected cells, whereby exposure
      concentrations are dependent on the availability and contaminant concentrations
      of different diet items in each cell. The model was applied to a selection of 10
      terrestrial vertebrate species, including six small mammalian and four top
      predator species. It was parameterized for cadmium contamination in a 285-ha,
      embanked floodplain area along the Rhine River in The Netherlands. Simulations of
      1,000 individuals for each species resulted in intraspecies variation in exposure
      concentrations of between 11 and 39%, with the smallest values generally
      corresponding to the species with the largest home ranges. Comparison of the
      model results with cadmium concentrations measured in four of the species from
      the study area showed that the predicted variation accounted for 12 to 16% of the
      variation in the measurements. This indicates that environmental heterogeneity
      governs a minor part of the variation in metal exposure concentrations that can
      actually be observed in river floodplains.

PMID- 18333679
TI  - Nanowastes and the environment: using mercury as an example pollutant to assess
      the environmental fate of chemicals adsorbed onto manufactured nanomaterials.
AB  - Emerging nanotechnologies hold great promise for creating new means of detecting
      pollutants, cleaning polluted waste streams, and recovering materials before they
      become wastes, thereby protecting environmental quality. Studies focusing on the
      different advantages of nanoscience and nanotechnology abound in the literature,
      but less research effort seems to be directed toward studying the fate and
      potential impacts of wastes that will be generated by this technology. Using a
      combination of biogeochemical and toxicological methods, we conducted a
      preliminary investigation of the potential environmental fate of Hg as an example
      pollutant bound to nanomaterials used in treatment of gas effluents. Methylation
      of Hg sorbed onto SiO(2)-TiO(2) nanocomposites was used as a proxy for Hg
      bioavailability to sedimentary microorganisms, and the FluoroMetPLATE assay was
      used to assess the toxicity of both virgin and Hg-loaded SiO(2)-TiO(2)
      nanocomposites. Our results show that the bioavailability of Hg sorbed onto
      SiO(2)-TiO(2) nanocomposites to sedimentary microorganisms is pH dependent, with
      decreasing reaction rates as the pH increases from 4 to 6. Toxicity tests
      conducted using liquid extracts obtained by leaching of Hg-loaded SiO(2)-TiO(2)
      nanocomposites with the synthetic precipitation leaching procedure solution
      showed an average inhibition of 84% (vs 57% for virgin SiO(2)-TiO(2)
      nanocomposites). These results suggest that Hg sorbed onto engineered
      nanoparticles could become bioavailable and toxic if introduced into natural
      systems. Accordingly, studies focusing on the environmental implications of
      nanomaterials should include determination of the fate and impacts of pollutants
      that enter the environment bound to engineered nanomaterials.

PMID- 18333680
TI  - Comparison of methods for evaluating acute and chronic toxicity in marine
      sediments.
AB  - Sublethal test methods are being used with increasing frequency to measure
      sediment toxicity, but little is known about the relative sensitivity of these
      tests compared to the more commonly used acute tests. The present study was
      conducted to compare the sensitivity of several acute and sublethal methods and
      to investigate their correlations with sediment chemistry and benthic community
      condition. Six sublethal methods (amphipod: Leptocheirus plumulosus survival,
      growth, and reproduction; polychaete: Neanthes arenaceodentata survival and
      growth; benthic copepod: Amphiascus tenuiremis life cycle; seed clam: Mercenaria
      mercenaria growth; oyster: Crassostrea virginica lysosome destabilization; and
      sediment-water interface testing with mussel embryos, Mytilus galloprovincialis)
      and two acute methods (amphipod survival with Eohaustorius estuarius and L.
      plumulosus) were used to test split sediment samples from stations in California.
      The test with Amphiascus proved to be the most sensitive sublethal test and the
      most sensitive overall, identifying 90% of the stations as toxic. The
      Leptocheirus 10-d test was the most sensitive of the acute tests, identifying 60%
      of the stations as toxic. In general, the sublethal tests were not more sensitive
      to sediments than the acute tests, with the sublethal tests finding an average of
      35% of the stations to be toxic while the acute found 44%. Of the sublethal
      tests, only the Amphiascus endpoints and Neanthes growth significantly (p <or=
      0.05) correlated with sediment chemical concentrations. Poor correspondence
      occurred between the toxicity endpoints and the indicators of benthic community
      condition. Differences in test characteristics such as mode of exposure, species
      specific contaminant sensitivity, changes in contaminant bioavailability, and
      influence of noncontaminant stressors on the benthos may have been responsible
      for variation in response among the tests and low correspondence with benthic
      community condition. The influence of these factors cannot be easily predicted,
      underscoring the need to use multiple toxicity methods, in combination with other
      lines of evidence, to provide an accurate and confident assessment of sediment
      toxicity.

PMID- 18333681
TI  - Modeling the toxicity of copper and zinc salts to wheat in 14 soils.
AB  - Interest is mounting in developing and utilizing soil-specific soil quality
      guidelines. This requires quantifying the effects that soil physicochemical
      properties have on various ecotoxicological endpoints, including phytotoxicity.
      To this end, 14 agricultural soils from Australia with differing soil properties
      were spiked with copper (Cu) and zinc (Zn) salts and used to conduct 21-d plant
      growth inhibition tests using wheat (Triticum aestivum L.) in pot trials. The
      toxicity of Cu and Zn was similar with 10% effect concentration (EC10) values
      ranging from 110 to 945 and from 235 to 965 mg/kg, respectively, while the
      corresponding median effect concentration (EC50) values ranged from 240 to 1,405
      and 470 to 1,745 mg/kg, respectively. Copper toxicity values (EC10, EC20, and
      EC50) were best modeled by the logarithm of cation exchange capacity (CEC) and
      either soil pH or electrical conductivity. Zinc EC50 and EC20 values were best
      modeled using the logarithm of CEC, while the EC10 data were best modeled using
      soil pH and the logarithm of organic carbon. These models generally estimated
      toxicity within a factor of two of the measured values.

PMID- 18333682
TI  - Aquatic fate and effects of Bacillus thuringiensis Cry3Bb1 protein: toward risk
      assessment.
AB  - Genetically engineered crops expressing Bacillus thuringiensis (Bt) insecticidal
      crystalline (Cry) proteins became commercially available in the United States in
      1996. In 2006, 19 million ha of Bt corn were planted worldwide, which represents
      a 10 million ha increase in 10 years. The sustainability of Bt crops is
      important, because their use has significantly reduced the amount of chemical
      insecticides necessary to control agricultural pests. Despite the high adoption
      rates of this novel insecticide, little is known about the aquatic fate of
      transgenic Bt proteins and their nontarget effects on aquatic invertebrates,
      although several potential routes exist for their transport to aquatic systems.
      Methods were developed to investigate the aquatic fate of transgenic Bt proteins
      and to determine their potential effects on nontarget aquatic invertebrates.
      Laboratory microcosms containing pond water only or pond water and sediment were
      used to examine the fate of the coleopteran-active Bt Cry3Bb1 protein in
      decomposing transgenic corn event MON863 (hereafter referred to as MON863 corn)
      leaf, stalk, and root. A half-life of less than 3 d was found for Bt Cry3Bb1 from
      decomposing MON863 corn residue. No Bt Cry3Bb1 was measured in the pond water or
      sediment extracts of microcosms containing MON863 corn. In an acute, static,
      partial-renewal toxicity test, Bt Cry3Bb1 protein from MON863 root extracts was
      fed to Chironomus dilutus larvae for 10 d. A significant decrease in C. dilutus
      survival at nominal concentrations of 30 ng/ml was found; however, no effect on
      growth among the surviving larvae was observed.

PMID- 18333683
TI  - Inorganic arsenic speciation in soil and groundwater near in-service chromated
      copper arsenate-treated wood poles.
AB  - The environmental impact of chromated copper arsenate (CCA)-treated utility poles
      is linked to the possible soil and groundwater contamination with arsenic. The
      objective of the present study was to determine the arsenic speciation in soil
      and groundwater near in-service CCA-treated poles. Arsenite (As[III]) and
      arsenate (As[V]) concentrations were determined in 29 surface and subsurface soil
      samples collected near eight CCA-treated wood poles. Temporal variability of
      total arsenic concentrations and inorganic arsenic speciation was also assessed
      in groundwater at two sites through four sampling events over a 19-month period.
      Arsenic speciation was carried out by a solvent extraction method using ammonium
      pyrrolidine dithiocarbamate-methyl isobutyl ketone, and total arsenic was
      quantified by inductively coupled plasma/atomic emission spectrometry/hydride
      generation. Average arsenic concentrations in surface soils immediately adjacent
      to utility poles ranged from 153+/-49 to 410+/-150 mg/kg but approached
      background levels (below 5 mg/kg) within 0.50 m from the poles. A positive
      correlation was found between surface soil As concentration and total Fe content.
      In subsurface samples (0.50 m), arsenic levels were generally high in sandy soils
      (up to 223+/-32 mg/kg), moderate in clayey soils (up to 126+/-26 mg/kg), and
      relatively lower in organic soils (up to 56+/-24 mg/ kg). Arsenic(V) was the
      predominant arsenic species in surface (>78%) and subsurface soils (>66%). Total
      arsenic concentrations in groundwater below the clayey site were high and varied
      widely over time (79-390 microg/L), with 30 to 68% as As(III). Below the utility
      pole located on the organic site with a high Fe content, lower total arsenic
      levels (12-33 microg/L) were found, with As(III) ranging from 0 to 100%.

PMID- 18333684
TI  - Influence of sediment ingestion and exposure concentration on the bioavailable
      fraction of sediment-associated tetrachlorobiphenyl in oligochaetes.
AB  - The desorption and bioavailability of 3,3',4,4'-tetrachlorobiphenyl (PCB 77) were
      studied in spiked natural sediments at six concentrations. The desorption
      kinetics were measured in a sediment-water suspension using Tenax resin
      extraction, and the bioavailability was measured by exposing Lumbriculus
      variegatus (Oligochaeta) to PCB 77-spiked sediment in a 14-d kinetic study. In
      addition, freely dissolved pore-water concentrations were measured using the
      polyoxymethylene solid-phase extraction method. The present study examined
      whether bioavailability can be defined more accurately by measuring the size of
      desorbing fractions and the pore-water concentrations than by using the standard
      equilibrium partitioning approach. The importance of ingested sediment in
      bioaccumulation also was investigated. Our data showed a clear, decreasing trend
      in the rapid-desorbing fractions and in the standard biota-sediment accumulation
      factors (BSAF) with increasing concentration in sediment. Desorbing fractions
      refined BSAFs were more uniform across the concentration treatments, and the pore
      water PCB 77 concentration predicted tissue concentrations close to observed
      values. In the risk assessment process, pore-water concentration or desorbing
      fractions would lead to more precise bioavailability estimates compared with
      those from the traditional equilibrium partitioning approach. The result also
      showed, however, that sediment-ingesting worms had access to an additional
      bioavailable chemical fraction that was especially evident when PCB 77 pore-water
      concentrations most likely approached the solubility limit. Thus, feeding may
      modify the bioavailable fraction that cannot be explained by simple equilibrium
      partitioning models.

PMID- 18333685
TI  - Species sensitivity distributions for suspended clays, sediment burial, and grain
      size change in the marine environment.
AB  - Assessment of the environmental risk of discharges, containing both chemicals and
      suspended solids (e.g., drilling discharges to the marine environment), requires
      an evaluation of the effects of both toxic and nontoxic pollutants. To date, a
      structured evaluation scheme that can be used for prognostic risk assessments for
      nontoxic stress is lacking. In the present study we challenge this lack of
      information by the development of marine species sensitivity distributions (SSDs)
      for three nontoxic stressors: suspended clays, burial by sediment, and change in
      sediment grain size. Through a literature study, effect levels were obtained for
      suspended clays, as well as for burial of biota. Information on the species
      preference range for median grain size was used to assess the sensitivity of
      marine species to changes in grain size. The 50% hazardous concentrations (HC50)
      for suspended barite and bentonite based on 50% effect concentrations (EC50s)
      were 3,010 and 1,830 mg/L, respectively. For burial the 50% hazardous level
      (HL50) was 5.4 cm. For change in median grain size, two SSDs were constructed;
      one for reducing and one for increasing the median grain size. The HL50 for
      reducing the median grain size was 17.8 mum. For increasing the median grain size
      this value was 305 mum. The SSDs have been constructed by using information
      related to offshore oil- and gas-related activities. Nevertheless, the results of
      the present study may have broader implications. The hypothesis of the present
      study is that the SSD methodology developed for the evaluation of toxic stress
      can also be applied to evaluate nontoxic stressors, facilitating the
      incorporation of nontoxic stressors in prognostic risk assessment tools.

PMID- 18333686
TI  - Oxidative stress, defense response, and early biomarkers for lead-contaminated
      soil in Vicia faba seedlings.
AB  - Chemical analyses and biological measurements were investigated in leaves of
      Vicia faba seedlings exposed to extraneous lead (Pb) at 0 to 2,000 mg/kg of soil
      for a month. The results showed that superoxide radical (O*(2)(-)) production,
      increased along with total Pb in leaves and available Pb in soil, resulted in
      enhancement of malondialdehyde and carbonyl groups. Antioxidant enzymes,
      including corresponding isoenzymes and heat shock protein 70 (hsp 70), were also
      enhanced to some extent. Significant changes were detected in the patterns and
      intensities of guaiacol peroxidase isoenzymes, while superoxide dismutase,
      catalase, and ascorbate peroxidase isoenzymes only changed intensities.
      Superoxide dismutase activities increased with the increase of extraneous Pb at 0
      to 500 mg/kg of soil and tended to decline thereafter, which might be responsible
      for the decrease of hydrogen peroxide and accumulation of O*(2)(-). Guaiacol
      peroxidase and ascorbate peroxidase enzymes were upregulated to become major
      scavengers of excess hydrogen peroxide on the condition of decreased catalase
      activities. Levels of hsp 70 were well correlated with Pb contents in leaves
      (r=0.777), O*(2)(-) accumulation (r = 0.985, p<0.01), and carbonyl groups
      (r=0.920, p<0.01) under extraneous Pb at 0 to 250 mg/kg of soil, suggesting that
      hsp 70 induced by O*(2)(-) was possibly involved in disposal of denatured
      proteins. The results showed that O*(2)(-), hsp 70, and guaiacol peroxidase
      isoenzymes had the most sensitive responses in the seedlings and these parameters
      could be potential early biomarkers of soil Pb contamination.

PMID- 18333687
TI  - Heating treatment schemes for enhancing chelant-assisted phytoextraction of heavy
      metals from contaminated soils.
AB  - Recent research has shown that chelant-assisted phytoextraction approaches often
      require a high dosage of chelant applied to soil. The present study focused on
      optimization of phytoremediation processes to increase the phytoextraction
      efficiency of metals at reduced chelant applications. Pot experiments were
      carried out to investigate the effects of increased soil temperature on shoot
      uptake of heavy metals by corn (Zea mays L.) and mung bean (Vigna radiat L.
      Wilczek) from heavy metal-contaminated soils. After the application of S,S
      ethylenediaminedisuccinic acid or ethylenediaminetetra-acetic acid, soils were
      exposed to high temperatures (50 or 80 degrees C) for 3 h, which significantly
      increased the concentration of heavy metals in shoots. The heating treatment 2 d
      after the chelant addition resulted in higher concentrations of metals compared
      with those treatments 2 d before or simultaneously with the chelant application.
      Irrigation with 100 degrees C water 2 d after the chelant addition, or irrigation
      with 100 degrees C chelant solutions directly, also resulted in significantly
      higher phytoextraction of metals in the two crops compared with 25 degrees C
      chelant solutions. In addition, a novel application method to increase soil
      temperature using underground polyvinyl chloride tubes would increase the chelant
      assisted extraction efficiency of Cu approximately 10- to 14-fold in corn and
      fivefold in mung bean compared with those nonheating treatments. In a field
      experiment, increasing soil temperature 2 d after chelant addition also increased
      the shoot Cu uptake approximately fivefold compared with those nonheating
      treatments. This new technique may represent a potential, engineering-oriented
      approach for phytoremediation of metal-polluted soils.

PMID- 18333688
TI  - Bioavailability and biodegradation of nonylphenol in sediment determined with
      chemical and bioanalysis.
AB  - The surfactant nonylphenol (NP) is an endocrine-disrupting compound that is
      widely spread throughout the environment. Although environmental risk assessments
      are based on total NP concentrations, only the bioavailable fraction possess an
      environmental risk. The present study describes the bioavailability and
      biodegradability of NP over time in contaminated river sediment of a tributary of
      the Ebro River in Spain. The bioavailable fraction was collected with Tenax TA(R)
      beads, and biodegradation was determined in aerobic batch experiments. The
      presence of NP was analyzed chemically using gas chromatography-mass spectrometry
      and indirectly as estrogenic potency using an in vitro reporter gene assay
      (ER(alpha)-luc assay). Of the total extractable NP in the sediment, 95%+/-1.5%
      (mean +/- standard error) desorbed quickly into the water phase. By aerobic
      biodegradation, the total extractable NP concentration and the estrogenic
      activity were reduced by 97%+/-0.5% and 94%+/-2%, respectively. The easily
      biodegradable fraction equals the potential bioavailable fraction. Only 43 to 86%
      of the estrogenic activity in the total extractable fraction, as detected in the
      ER(alpha)-luc assay, could be explained by the present NP concentration. This
      indicates that other estrogenic compounds were present and that their
      bioavailability and aerobic degradation were similar to that of NP. Therefore, we
      propose to use NP as an indicator compound to monitor estrogenicity of this Ebro
      River sediment. To what extent this conclusion holds for other river sediments
      depends on the composition of the contaminants and/or the nature of these
      sediments and requires further testing.

PMID- 18333689
TI  - Effects of different forms of nitrogen fertilizers on arsenic uptake by rice
      plants.
AB  - A pot microcosm experiment was conducted to investigate the effect of different
      forms of N fertilizers on As uptake by rice. Compared to a nontreated control,
      addition of nitrate reduced Fe(II) concentration in soil solution, while
      treatment with ammonium enhanced Fe(III) reduction, probably coupled to NH(4)(+)
      oxidation in the nonrhizosphere. Most-probable-number (MPN) enumerations revealed
      high densities of nitrate-dependent Fe(II)-oxidizing microorganisms. The addition
      of nitrate decreased Fe plaque formation on the root surface, accompanied by much
      lower dissolved Fe(II) concentrations in the rhizosphere soil solution compared
      to the nonamended control. Nitrate addition also reduced As uptake by the rice
      plant. These results suggest that nitrate may inhibit Fe(III) reduction and/or
      stimulate nitrate-dependent Fe(II) oxidation, leading to As coprecipitation with,
      or adsorption to, Fe(III) minerals in the soil. Although Fe plaque formation on
      the root surface is reduced, nitrate-dependent stimulation of Fe(II) oxidation
      and/or inhibition of Fe(III) reduction in the bulk soil sequesters mobile As in
      the soil, resulting in reduced As uptake by rice.

PMID- 18333690
TI  - Preliminary hazard assessment of polychlorinated biphenyls, polybrominated
      diphenyl ethers, and polychlorinated dibenzo-p-dioxins and dibenzofurans to
      Yangtze finless porpoise in Dongting Lake, China.
AB  - Yangtze finless porpoise (Neophocaena phocaenoides asiaeorientalis), a protected
      endangered species, is the sole freshwater subspecies of finless porpoise, living
      only in the middle and lower reaches of the Yangtze River, China, and its
      appended lakes. Its population has decreased sharply to 1,400 because of human
      activities, including environmental contamination. In the present study,
      polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and
      polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined in
      the blubber, liver, kidney, stomach, small intestine, and brains of five
      individual Yangtze finless porpoises collected from 1998 to 2004. The results
      showed PCB concentrations ranged from 0.06 to 1.89 microg/g lipid weight in the
      organs and consisted mainly of penta-, hexa-, and decachlorinated biphenyls. The
      PBDE concentrations were between 5.32 and 72.76 ng/g lipid weight. Tetra-, penta
      , and hexabrominated diphenyl ethers were the major homologues. The PCDD/F
      concentrations ranged from 65 to 1,563 pg/g lipid weight, and their predominant
      homologues were penta- and hexachlorinated dibenzofurans and hepta- and
      octachlorinated dibenzo-p-dioxins. The hazard quotients (HQs) based on toxic
      equivalency were determined to be greater than one in all individuals for PCBs,
      for PCDD/Fs, and for PCBs and PCDD/Fs In addition, HQs would be higher if PBDEs
      were included. The results suggest that reduction of environmental contamination
      may contribute greatly to protecting this highly endangered species.

PMID- 18333691
TI  - Partitioning and matrix-specific toxicity of bifenthrin among sediments and leaf
      sourced organic matter.
AB  - Synthetic pyrethroids readily partition from the aqueous to the solid phase in
      aquatic systems. Previous work has focused on pyrethroid partitioning to sediment
      matrices. Within many aquatic systems, however, other carbon-containing materials
      are present and can be critically important to certain invertebrate species and
      ecosystem functioning. For example, some invertebrates readily process leaf
      material, and these processes may represent an additional route of contaminant
      exposure. To our knowledge, estimates for partitioning of pyrethroids to these
      nondissolved organic matter matrices and associated toxicity have not been
      examined. The objectives of the present study were to examine variation in
      organic carbon (OC)-based partition coefficient (K(OC)) among three size
      fractions of particulate organic matter from sugar maple (Acer saccharum) leaf
      litter and sediments for the pyrethroid insecticide bifenthrin and to examine
      variation in toxicity to Hyalella azteca among bifenthrin-bound organic matter
      matrices and sediment. Log K(OC) of [(14)C]bifenthrin was greatest within
      sediment (6.63+/-0.23; mean +/- standard deviation throughout) and lowest in
      coarse particulate leaf material (4.86+/-0.03). The H. azteca median lethal
      concentration was 0.07, 0.11, and 0.15 microg/g OC for leaf material, sediment,
      and a 50% mix of leaf and sediment, respectively. Nonoverlapping 95% confidence
      intervals occurred between the leaf treatment and the leaf-sediment treatment.
      This pattern was supported in an additional experiment, and at 0.22 microg/g OC,
      H. azteca survival was greater in the leaf-sediment mixture than in sediment or
      in leaf material alone (F=29.5, p<0.0001). In systems that contain sediment and
      leaf material, both greater partitioning of bifenthrin to the sediment fraction
      and preferential use of leaf substrates may drive H. azteca survival.

PMID- 18333692
TI  - Evaluation of sample preparation methods for nuclear magnetic resonance metabolic
      profiling studies with Eisenia fetida.
AB  - The earthworm Eisenia fetida is frequently used in ecotoxicological studies;
      however, it has not yet been investigated using proton nuclear magnetic resonance
      ((1)H NMR) metabolic profiling methods. The present study investigates the impact
      of depuration time, sample homogenization, and different extraction solvents on
      the quality and reproducibility of the (1)H NMR spectra of E. fetida with the
      goal of determining whether this species is suitable for future metabonomic
      studies. A depuration time of 96 h, followed by intact lyophilization before
      homogenization and extraction into a deuterium oxide (D(2)O)-based phosphate
      buffer, was found to produce extracts with excellent (1)H NMR reproducibility.
      The D(2)O buffer extracted the largest quantity of the widest variety of
      earthworm metabolites, which is consistent with the results from other studies
      using different earthworm species. Nuclear magnetic resonance assignments of the
      major metabolites in the D(2)O-based buffer also were performed and found to be
      similar to those for other earthworm species, such as Eisenia veneta, but also to
      have characteristic attributes in E. fetida. The major metabolites identified
      include amino acids (alanine, arginine, glutamic acid, glutamine, glycine,
      leucine, lysine, phenylalanine, serine, tyrosine, and valine), two sugars
      (glucose and maltose), the sugar alcohol mannitol, and the polyalcohol inositol.
      Two other earthworm species (Lumbricus rubellus and Lumbricus terrestris) also
      were examined using protocols developed for E. fetida, and of the three species,
      the (1)H NMR spectra of E. fetida had the least variation, indicating this
      species is well-suited for future metabolomic-based ecotoxicity studies.

PMID- 18333693
TI  - Membrane-water partitioning, membrane permeability, and baseline toxicity of the
      parasiticides ivermectin, albendazole, and morantel.
AB  - A comparative hazard assessment of the antiparasitics ivermectin, albendazole,
      and morantel was performed, with a particular focus on bioavailability and uptake
      into biological membranes. The experimentally determined liposome-water
      distribution ratio at pH 7 (D(lipw) (pH 7)) of the positively charged morantel
      was 100 L/kg lipid. The D(lipw) (pH 7) of albendazole was 3,000 L/kg lipid. The
      membrane permeability determined with the parallel artificial membrane
      permeability assay was consistent with predictions from a quantitative structure
      activity relationship (QSAR) for morantel but 14-fold lower than predicted for
      albendazole, which can be rationalized because neutral albendazole is, in fact,
      zwitterionic and the large dipole moment hinders permeation through hydrophobic
      membranes. An unusually large molecule, ivermectin was suspected to show
      decreased bioaccumulation because of its bulkiness, but experimental
      determination of solubility showed that it was 40-fold less soluble than expected
      from a QSAR between solubility and the octanol-water partition coefficient. In
      contrast, its membrane permeability appeared to be typical for a compound of the
      given hydrophobicity, but it was not possible to determine the membrane-water
      partition coefficient because of its low solubility and high affinity to the
      dialysis membrane of the experimental device. The D(lipw) (pH 7) for ivermectin
      of 2,700 L/kg lipid was calculated with a QSAR model. Morantel and albendazole
      were baseline toxicants in the bioluminescence inhibition test with Vibrio
      fischeri and a test for inhibition of photosynthesis in green algae. Only
      ivermectin exhibited a specific effect toward algae, but the excess toxicity was
      not very pronounced and might be biased by the uncertainty of the estimated
      hydrophobicity descriptor. Overall, we did not find any unexpected effect on
      nontarget endpoints.

PMID- 18333694
TI  - Using fluorescent aromatic compounds in bile from juvenile salmonids to predict
      exposure to polycyclic aromatic hydrocarbons.
AB  - We provide data from four different studies in which fish were fed polycyclic
      aromatic hydrocarbons (PAHs) that were used to develop a predictive relationship
      between dose (mug/g fish/d) and metabolites of PAHs in bile. Juvenile salmonids
      were fed various doses of total PAH that were applied as a mixture to fish
      pellets. The number of PAHs in each mixture ranged from 10 to 21 different low-
      and high-molecular-weight compounds, and their relative proportions and abundance
      were based on stomach concentrations observed for field-collected fish. Although
      we examined both the phenanthrene (PHN) and benzo[a]pyrene signals for the
      fluorescent aromatic compounds (FACs) in bile, the PHN signal exhibited the
      highest correlation and was considered to be the better choice for predicting
      exposure. A large database of PHN FAC values for field-collected fish was
      examined and used to predict dose by the method of inverse prediction. The goal
      of the present study was to develop a predictive relationship that would allow
      estimation of an exposure dose for an observed value of PHN FACs from juvenile
      salmonids sampled in the field. This dose would then be used to estimate adverse
      effects based on toxicity results from laboratory studies. Additional analyses
      were performed to determine ventilation doses from water concentrations of total
      PAH and then relate those to PHN FAC values.

PMID- 18333695
TI  - Estrogenic effects of polychlorinated biphenyls and relation to cytochrome P4501A
      activity in the endangered goodeid fish Ameca splendens.
AB  - The present study examines the relationships between cytochrome P4501A (CYP1A)
      activity and vitellogenin (VTG) induction in Ameca splendens elicited by a
      polychlorinated biphenyl (PCB) mixture. Ethoxyresorufin-O-deethylase (EROD)
      activity, mRNA levels of VTG, and VTG induction were evaluated in male and female
      fish exposed for 1, 2, 4, 8, and 16 d to a commercial PCB mixture.
      Polychlorinated biphenyls induced higher EROD in both sexes and this induction
      was higher in females than in males. Maximum EROD and VTG induction occurred on
      day 1 in females, while in males these maxima occurred on days 8 and 16. A
      correlation between EROD and VTG induction was found only in males (p<0.001), and
      VTG induction was also higher in males than in females (p<0.01). Exposure to PCBs
      elicited increases in VTG expression and induction over time in males, while in
      females these decreased at the end of the exposure period. Deficiencies in the
      feedback mechanisms of male A. splendens exposed in the wild to xenoestrogens
      such as PCBs have probably contributed to alter the sex ratio of wild populations
      of this species.

PMID- 18333696
TI  - Identifying the cause and source of sediment toxicity in an agriculture
      influenced creek.
AB  - Del Puerto Creek, an agriculturally influenced stream in northern California,
      USA, with a history of sediment toxicity, was used as a case study to determine
      the feasibility of using sediment toxicity testing and chemical analysis to
      identify the causative agent for the toxicity and its sources. Testing with the
      amphipod Hyalella azteca confirmed historical toxicity and identified a point
      along the creek at which there was an abrupt increase in sediment toxicity that
      persisted for at least 6 km downstream. Three recently developed whole sediment
      toxicity identification evaluation manipulations, temperature reduction,
      piperonyl butoxide addition, and esterase addition, were applied to sediment from
      one site and were suggestive of a pyrethroid as the cause for toxicity. Utilizing
      published median lethal concentration (LC50) values in a toxic unit analysis, the
      pyrethroid insecticide bifenthrin was identified as the primary contributor to
      toxicity in nearly all sites at which toxicity was observed, with occasional
      additional contributions from the pyrethroids lambda-cyhalothrin, esfenvalerate,
      and cyfluthrin. Most agricultural drains discharging to Del Puerto Creek
      contained bifenthrin in their sediments at concentrations near or above acutely
      toxic concentrations. However, only one drain contained sediments with bifenthrin
      concentrations approaching the concentrations measured in creek sediments. This
      fact, along with the proximity of that particular discharge to the location in
      the creek with the highest concentrations, suggested that one drain may be
      responsible for much of the toxicity and pyrethroid residues in creek sediments.
      The methods employed in this study are likely to be of considerable value in
      total maximum daily load efforts in Del Puerto Creek or other California surface
      water bodies known to have pyrethroid-related aquatic toxicity.

PMID- 18333697
TI  - Uncertainty analysis of dioxin-like polychlorinated biphenyls-related toxic
      equivalents in fish.
AB  - The toxic equivalent (TEQ) concept is widely used to assess toxicity potential of
      a dioxin-like chemical mixture. The TEQ approach converts concentrations of
      various dioxin-like compounds into a single concentration that is toxicologically
      equivalent to the most toxic dioxin compound, 2,3,7,8-tetrachlorodibenzo-p-dioxin
      (2,3,7,8-TCDD), using toxic equivalency factors (TEFs). It has been shown that in
      the absence of costly measurements of dioxin-like polychlorinated biphenyls (dl
      PCBs) in fish, relatively inexpensive measurements of total PCB can be utilized
      to estimate dl-PCB-related TEQ (i.e., TEQ(dl-PCB)). The present study assesses
      the impacts of uncertainties in dl-PCB measurements and estimates, and mammalian
      TEFs on TEQ(dl-PCB) using the Monte Carlo technique. The analysis suggests that
      measurement errors for dl-PCBs translate into up to 1.3-fold uncertainty in
      TEQ(dl-PCB), while uncertainties in estimates of dl-PCBs generally produce up to
      a threefold uncertainty in TEQ(dl-PCB). In contrast, the uncertainty due to TEFs
      normally ranges 10- to 13-fold and spans over 30- to 40-fold under extreme cases.
      For 2005 TEFs, PCB-126 is the dominating contributor to uncertainty in TEQ(dl
      PCB). When we considered uncertainties in the TEFs and estimated dl-PCB
      concentrations simultaneously, there was little increase in uncertainty in TEQ(dl
      PCB) that was already produced by the TEFs only. These results indicate that the
      dl-PCB composition in fish and/or the relationship between total PCB and TEQ(dl
      PCB) can be utilized to estimate TEQ(dl-PCB) with reasonable confidence.

PMID- 18333698
TI  - Dietary uptake models used for modeling the bioaccumulation of organic
      contaminants in fish.
AB  - Numerous models have been developed to predict the bioaccumulation of organic
      chemicals in fish. Although chemical dietary uptake can be modeled using
      assimilation efficiencies, bioaccumulation models fall into two distinct groups.
      The first group implicitly assumes that assimilation efficiencies describe the
      net chemical exchanges between fish and their food. These models describe
      chemical elimination as a lumped process that is independent of the fish's
      egestion rate or as a process that does not require an explicit fecal excretion
      term. The second group, however, explicitly assumes that assimilation
      efficiencies describe only actual chemical uptake and formulates chemical fecal
      and gill excretion as distinct, thermodynamically driven processes. After
      reviewing the derivations and assumptions of the algorithms that have been used
      to describe chemical dietary uptake of fish, their application, as implemented in
      16 published bioaccumulation models, is analyzed for largemouth bass (Micropterus
      salmoides), walleye (Sander vitreus = Stizostedion vitreum), and rainbow trout
      (Oncorhynchus mykiss) that bioaccumulate an unspecified, poorly metabolized,
      hydrophobic chemical possessing a log K(OW) of 6.5 (i.e., a chemical similar to a
      pentachlorobiphenyl).

PMID- 18333699
TI  - Female pattern hair loss may be triggered by low oestrogen to androgen ratio.
AB  - OBJECTIVE: In both sexes the androgenetic alopecia is known to be mediated by the
      conversion of circulating androgens into dihydrotestosterone within the hair
      follicle. However, there are a number of differences between male and female
      pattern baldness with estrogen known to be protective against hair loss in women.
      Since androgen levels in women with female pattern hair loss are mostly within
      the normal range, we decided to calculate the ratio of estrogens to androgens in
      order to find a putative trigger for their hair loss. METHODS: We studied 20
      premenopausal women with female pattern hair loss and 9 healthy women for serum
      levels of LH, FSH, estradiol, free and total testosterone, sex hormone binding
      globulin (SHBG) and dehydroepiandrosterone sulfate (DHEAS) on the first day of
      their menstrual cycle. RESULTS: Although the absolute levels of androgens were
      normal in both groups, the ratio of estradiol to free testosterone and the ratio
      of estradiol to DHEAS were significantly lower in patients than in the control
      group. CONCLUSIONS: We put up a hypothesis that in the presence of a genetic
      susceptibility, it is the estrogen to androgen ratio, as represented by the ratio
      of estradiol to free testosterone that might be responsible for triggering female
      pattern hair loss in women.

PMID- 18333700
TI  - Health resort treatment improved the neurosteroid profile in thyroidectomized
      women.
AB  - OBJECTIVE: The aim was to study the effect of climatotherapy and spa treatment on
      selected neuro- and immunomodulatory steroids known to affect well-being, and
      homocysteine, in a homogenous group of thyroidectomized women under standard
      substitution regime. METHODS: Dehydroepiandrosterone, its precursors and
      metabolites, cortisol, major sex steroids, SHBG, and homocysteine were measured
      before and after three-weeks stay in a health resort Jesenik (Graefenberg) in
      Czech Republic. The studied group consisted of 21 women after total thyroidectomy
      which was performed at least 3 months before the admission to the spa resort. All
      patients received thyroid hormone substitution treatment which was not changed
      during their stay in that resort. RESULTS: Out of the steroids investigated,
      five, namely dehydroepiandrosterone, androstenedione, testosterone, 7beta-hydroxy
      dehydroepiandrosterone and cortisol were changed significantly after treatment.
      The most considerable was the decrease of cortisol and of homocysteine (p < 0.000
      each). CONCLUSION: Spa resort treatment of thyroidectomized women substituted
      with thyroid hormones resulted in significant, mostly beneficial effects on
      steroid spectrum. This effect was achieved without any use of psychopharmacs.

PMID- 18333701
TI  - Hormone response to stress in rat strains of different susceptibility to
      immunologic challenge.
AB  - OBJECTIVE: The aim of this study was to compare the changes in plasma levels of
      hormones involved in modulation of the immune system function after exposure to
      stress in two rat strains with different susceptibility to immunoantigens.
      METHODS: Adult rat males of Lewis (LEW) and Fischer 344 (FIS) strains were
      exposed to restrain stress for 2 hours and blood samples were collected during
      stress exposure. Other groups of animals were exposed to restrain stress for 2
      hours and sacrificed 3 hours later for blood and organ collection.
      Corticosterone, testosterone, dehydroepiandrosterone, 17beta-estradiol and
      progesterone were estimated by radioimmunoassay, epinephrine and norepinephrine
      levels were determined by radioenzymatic method. RESULTS: The levels of plasma
      corticosterone and catecholamines were significantly higher during stress
      exposure in FIS as compared to LEW rats. Greater decrease of testosterone levels
      and higher levels of estradiol were noted after exposure to stress in LEW rats.
      Higher values of progesterone plasma levels were noted in FIS rats after stress.
      CONCLUSIONS: These results demonstrated the differences in the response of
      catecholamines, adrenal and gonadal steroids after exposure to stress in LEW and
      FIS rats with lower levels of hormones with anti-inflammatory action in LEW rats.

PMID- 18333702
TI  - The relation between pure papillary and follicular variant in papillary thyroid
      carcinoma.
AB  - OBJECTIVE: Pure papillary thyroid carcinoma and the follicular variant papillary
      thyroid carcinoma are the most common subtypes of papillary thyroid carcinoma.
      The aim of this study was to investigate the effects of prognostic factors of
      these two subgroups in our series. PATIENTS AND METHODS: Histopathological type
      of carcinoma was retrospectively revised in 199 patients who were then divided
      according to such type. Patients' age and gender as well as the size and
      multicentricity of tumor, association with Hashimoto's thyroiditis, serum
      thyroglobulin and anti-thyroglobulin antibodies levels, metastatic lymph node and
      distant metastases status for both groups were evaluated. RESULTS: Gender, size,
      multicentricity of tumor, serum thyroglobulin and anti-thyroglobulin levels were
      similar in both groups. It was found that, although the tumor size of pure
      papillary thyroid carcinoma was smaller than that of follicular variant papillary
      thyroid carcinoma, lymph node metastases occurred more frequently when both
      subgroups were examined. CONCLUSION: The pathological and clinical signs of pure
      papillary thyroid carcinoma and follicular variant papillary thyroid carcinoma
      were found similar. According to these results, this study does not support the
      literature which claims that follicular variant papillary thyroid carcinoma is
      more aggressive than pure papillary thyroid carcinoma. Moreover, it could be
      assumed that the number of patients who are diagnosed as pure papillary thyroid
      carcinoma may be higher when associated with Hashimoto's thyroiditis.

PMID- 18333703
TI  - Daytime melatonin treatment influences food carrying (hoarding) behavior in rats.
AB  - OBJECTIVE: Three experiments were performed to verify whether melatonin (MEL) may
      influence hoarding behavior in rats. This hypothesis was supported by the
      consideration that leptin treatment decreases food hoarding in hamsters and that
      an inverse relation exists between plasma leptin concentration and MEL treatment.
      METHODS: Male Sprague-Dawley rats housed individually and kept on 12h:12h light
      dark cycle were used. First experiment was performed to check whether a bimodal
      distribution of food hoarding scores exists in rats, and to select two groups of
      high (HH-rats) or low (LH-rats) hoarding. Second experiment was designed to
      verify whether MEL treatment modifies food-hoarding, while the third one was
      performed to investigate whether MEL treatment was able to modify the reciprocal
      relation between leptin and MEL plasma concentration. RESULTS: In rats the
      hoarding tendency fell into a bimodal distribution and the plasma leptin
      concentration was significantly higher in HH-rats than LH-rats. When MEL was
      injected, circulating concentration of leptin was decreased in both HH-rats and
      LH-rats and such MEL treatment significantly increased the number of pellets
      hoarded by LH-rats but not that hoarded by HH-rats. CONCLUSIONS: MEL influences
      the food-hoarding in rats either directly, or indirectly by the MEL and leptin
      reciprocal interaction. Our results support the hypothesis that the endocrine
      system either directly, by the action of one or more combined hormones (MEL,
      leptin), or indirectly via its actions on neural substrates determines, at least
      in part, food-hoarding of rats.

PMID- 18333704
TI  - Major depression associated with rates of cardiovascular disease state
      transitions.
AB  - OBJECTIVE: To compare patients with and without major depression with respect to
      their rates of transition to several stages of cardiovascular disease
      progression. STUDY DESIGN: Retrospective observational study. METHODS: The study
      used administrative data from a large insurer in Hawaii to evaluate associations
      of major depression with cardiovascular progression. Analyses used competing
      risks models, models that allow more than 1 type of possible outcome event at the
      transition stages. All analyses were adjusted for age and sex. RESULTS: Among
      nearly 600,000 healthy members, those with major depression in the past year were
      50% to 100% more likely than controls to develop hypertension or dyslipidemia.
      Rates were increased to a similar magnitude (1) among patients with hypertension
      or dyslipidemia who subsequently developed either the other condition or coronary
      artery disease and (2) among patients with hypertension and dyslipidemia who
      developed coronary artery disease or congestive heart failure. Transition rates
      to coronary artery disease or congestive heart failure also were increased 50% to
      100% among patients with diabetes, hypertension, and dyslipidemia. The sequence
      of associations remained as strong examining depression 1-2 years in the past as
      with depression in the past year. CONCLUSIONS: The results show a pattern of
      faster transitions for patients with major depression compared with patients
      without major depression across both the early and later stages of cardiovascular
      progression. Health plans offer a setting where patients with depression can be
      identified and where interventions might be undertaken to minimize the possible
      effects of depression on transition rates.

PMID- 18333705
TI  - Self-monitoring of blood glucose in type 2 diabetes: cost-effectiveness in the
      united states.
AB  - OBJECTIVE: This study was designed to model the cost-effectiveness of self
      monitoring of blood glucose (SMBG) at frequencies of 1 or 3 times per day for
      patients with type 2 diabetes mellitus (T2DM) who are treated with oral
      antidiabetic (OAD) medications within the United States. STUDY DESIGN: Based on a
      Kaiser Permanente study showing glycosylated hemoglobin (HbA1C) improvements
      related to SMBG frequency, a validated model was used to project 40-year clinical
      and economic outcomes for SMBG at 1 or 3 times per day vs no SMBG. METHODS:
      Baseline mean HbA1C (8.6%), age, and sex of the simulated cohort came from the
      Kaiser analysis of new SMBG users of OAD agents for T2DM. Other cohort
      characteristics, transition probabilities, utilities, and direct costs (from a US
      public payer perspective) were derived from relevant literature. Outcomes were
      discounted at 3% per annum, with sensitivity analyses performed on discount rates
      and time horizons. RESULTS: Compared with no SMBG, quality-adjusted life
      expectancy increased with SMBG frequency. Increases were 0.103 and 0.327 quality
      adjusted life-years (QALYs) for SMBG at 1 and 3 times per day, respectively.
      Corresponding incremental cost-effective ratios (ICERs) were $7856 and $6601 per
      QALY gained. Results indicate that SMBG at both 1 and 3 times per day in this
      cohort of patients with T2DM taking OADs would represent good value for money in
      the United States, with ICERs being most sensitive to the time horizon.
      CONCLUSIONS: Longer time horizons generally led to greater SMBG cost
      effectiveness. The ICER for SMBG 3 times per day was $518 per QALY over a 10-year
      time horizon, indicating very good value.

PMID- 18333706
TI  - Care coordination to increase referrals to smoking cessation telephone
      counseling: a demonstration project.
AB  - OBJECTIVE: To test the effectiveness of a care coordination program for telephone
      counseling in raising referral and treatment rates for smoking cessation. STUDY
      DESIGN: A demonstration project implementing a smoking cessation care
      coordination program offering telephone counseling and medication management to
      patients referred from primary care. METHODS: The study was performed at 18
      Veterans Health Administration (VA) sites in California. Participants were VA
      patients receiving primary care. We randomly allocated 10 of 18 sites to receive
      the Telephone Care Coordination Program, which included simple 2-click referral,
      proactive care coordination, medication management, and 5 follow-up telephone
      calls. Each patient received a 30- to 45-minute counseling session from the
      California Smokers' Helpline. Patients at control sites received usual care.
      RESULTS: During 10 months, we received 2965 referrals. We were unable to reach
      1156 patients (39%), despite at least 3 attempts. We excluded 73 patients (3%),
      and 391 patients (13%) were not interested. We connected the remaining 1345
      patients (45%) to the Helpline. At 6-month followup, 335 patients (11% of all
      referrals and 25% of participating patients) were abstinent. Providers at
      intervention sites reported referring many more patients to telephone counseling
      than providers at control sites (15.6 vs 0.7 in the prior month). CONCLUSIONS:
      The program generated a large number of referrals; almost half of the patients
      referred were connected with the Helpline. Long-term abstinence was excellent.
      These results suggest that managed care organizations may be able to improve
      tobacco control by implementing a similar system of care coordination.

PMID- 18333707
TI  - Can managed care organizations partner with manufacturers for comparative
      effectiveness research?
AB  - OBJECTIVE: To describe 2 published pragmatic or practical clinical trials (PCTs)
      as case studies illustrating successful partnerships between managed care
      organizations (MCOs) and pharmaceutical manufacturers. STUDY DESIGN: In today's
      environment, there is increasing concern about the comparative effectiveness of
      medical interventions. Various opinion leaders and stakeholders lament the dearth
      of such evidence and are calling for the public and private sectors to invest up
      to billions of dollars to create better comparative evidence. METHODS: We
      selected 2 PCTs conducted at different points in the drug life cycle to highlight
      strengths, limitations, and policy implications. The phase IV study compared
      fluoxetine hydrochloride vs 2 generic tricyclic antidepressants in selected
      primary care clinics of a health maintenance organization from 1992 through 1994.
      The phase IIIb study compared daily budesonide via dry powder inhaler vs
      triamcinolone acetonide metered-dose inhaler in adult patients with persistent
      asthma in 25 MCOs from 1995 through 1998. RESULTS: Both PCTs were successfully
      sponsored and funded by pharmaceutical manufacturers in collaboration with MCOs
      and provided potentially useful evidence of real-world effectiveness and evidence
      of value to healthcare decision makers. CONCLUSIONS: Industry-sponsored PCTs in
      managed care are feasible when manufacturer and MCO incentives align and can
      provide real-world evidence of comparative effectiveness and value for money.
      These trials can be conducted successfully in the phase IIIb and phase IV
      environments.

PMID- 18333708
TI  - Risk adjusting community-acquired pneumonia hospital outcomes using automated
      databases.
AB  - OBJECTIVE: To describe the development and assessment of the Abbreviated Fine
      Severity Score (AFSS), a simplified version of the Pneumonia Severity Index (PSI)
      suitable for providing risk-adjusted reports to clinicians caring for patients
      hospitalized with community-acquired pneumonia. STUDY DESIGN: Retrospective
      cohort study. METHODS: We defined the AFSS based on data available in
      administrative and laboratory databases. We downloaded and linked these
      hospitalization and laboratory data from 2 cohorts (11,030 patients and 6147
      patients) hospitalized with community-acquired pneumonia in all Kaiser Permanente
      Medical Care Program hospitals in northern California. We then assessed the
      relationship between the AFSS and mortality, length of stay, intensive care unit
      admission, and the use of assisted ventilation. Using logistic regression
      analysis, we assessed the performance of the AFSS and determined the area under
      the receiver operating characteristic curve (c statistic). Using a combination of
      manual and electronic medical record review, we compared the AFSS with the full
      PSI in 2 subsets of patients in northern California and Denver, Colorado, whose
      medical records were manually reviewed. RESULTS: The AFSS compares favorably with
      the PSI with respect to predicting mortality. It has good discrimination with
      respect to inhospital (c = 0.74) and 30-day (c = 0.75) mortality. It also
      correlates strongly with the PSI (r = 0.87 and r = 0.93 in the 2 medical record
      review subsets). CONCLUSIONS: The AFSS can be used to provide clinically relevant
      risk-adjusted outcomes reports to clinicians in an integrated healthcare delivery
      system. It is possible to apply risk-adjustment methods from research settings to
      operational ones.

PMID- 18333709
TI  - The effect of disease management on utilization of services by race/ethnicity:
      evidence from the Florida Medicaid program.
AB  - OBJECTIVE: To measure possible racial/ethnic differences in a Florida disease
      management (DM) program on utilization of selected healthcare services for 4
      chronic illnesses. STUDY DESIGN: Pre-post comparison of utilization among 15,275
      high-risk beneficiaries enrolled in DM in the Florida Medicaid program between
      October 2001 and October 2003. METHODS: Two-part regression analyses of the
      effect of DM on annualized inpatient days, emergency department (ED) visits, and
      outpatient visits, controlling for relevant covariates. Annualized rates were
      used to adjust for differences in length of program enrollment. RESULTS: Disease
      management patients in the postperiod had significantly lower annual rates of
      inpatient days, ED visits, and outpatient visits across most racial/ethnic
      groups. Disease management reduced utilization by a similar absolute amount in
      each racial/ethnic group. However, baseline disparities in utilization of
      inpatient days were not reduced by the DM program. CONCLUSIONS: Disease
      management has a similar effect across different racial/ethnic groups but may not
      ameliorate important baseline disparities. Evaluations of DM programs should
      account for baseline disparities in utilization and examine whether those
      disparities can be reduced through DM.

PMID- 18333710
TI  - Animal experimentation: the need for deliberation and challenge.

PMID- 18333711
TI  - An evaluation of the predictive ability of the QSAR software packages, DEREK,
      HAZARDEXPERT and TOPKAT, to describe chemically-induced skin irritation.
AB  - According to the REACH chemicals legislation, formally adopted by the EU in 2006,
      Quantitative Structure-Activity Relationships (QSARs) can be used as alternatives
      to animal testing, which itself poses specific ethical and economical concerns. A
      critical assessment of the performance of the QSAR models is therefore the first
      step toward the reliable use of such computational techniques. This article
      reports the performance of the skin irritation module of three commercially
      available software packages: DEREK, HAZARDEXPERT and TOPKAT. Their performances
      were tested on the basis of data published in the literature, for 116 chemicals.
      The results of this study show that only TOPKAT was able to predict the
      irritative potential for the majority of chemicals, whereas DEREK and
      HAZARDEXPERT could correctly identify only a few irritant substances.

PMID- 18333712
TI  - Repeated exposure to benzalkonium chloride in the Ex Vivo Eye Irritation Test
      (EVEIT): observation of isolated corneal damage and healing.
AB  - The prediction of side-effects is a key issue in the REACH initiative on
      chemicals, in the production of cosmetics and in the preclinical testing of
      drugs. A new ex vivo test for repeated substance application is presented, that
      is able to identify corrosive and irritant effects on the eye by using crucial
      endpoints, such as cellular and morphological damage, and healing
      characteristics. The test is intended to replace the Draize eye test and to
      improve the preclinical testing of drugs and chemicals that are likely to come
      into direct contact with the cornea. The Ex Vivo Eye Irritation Test (EVEIT) is a
      self-healing system, involving living corneas obtained from abattoir rabbit eyes.
      The corneas are cultured in a similar way to the method used during the
      transplantation of corneal grafts. The corneas are exposed to multiple small,
      mechanical abrasions, and then test substances are repeatedly dropped onto the
      centres of the corneas. The test substances applied in this study were citrate
      buffered hyaluronate eye drops and an artificial tear replacement, with
      increasing concentrations of up to 0.1% benzalkonium chloride. A dose-dependent
      inhibition of recovery and impairment of the lactate production mechanism in the
      cornea was observed with benzalkonium chloride treatment.

PMID- 18333713
TI  - A comparative evaluation of corneal epithelial cell cultures for assessing ocular
      permeability.
AB  - The purpose of this study was to evaluate the potential value of different
      epithelial cell culture systems as in vitro models for studying corneal
      permeability. Transformed human corneal epithelial (HCE-T) cells and Statens
      Serum Institut rabbit corneal (SIRC) cells were cultured on permeable filters.
      SkinEthic human corneal epithelium (S-HCE) and Clonetics human corneal epithelium
      (C-HCE) were received as ready-to-use systems. Excised rabbit corneas (ERCs) and
      human corneas (EHCs) were mounted in Ussing chambers, and used as references.
      Barrier properties were assessed by measuring transepithelial electrical
      resistance, and by determining the apparent permeability of markers with
      different physico-chemical properties, namely, fluorescein, sodium salt;
      propranolol hydrochloride; moxaverine hydrochloride; timolol hydrogenmaleate; and
      rhodamine 123. SIRC cells and the S-HCE failed to develop epithelial barrier
      properties, and hence were unable to distinguish between the permeation markers.
      Barrier function and the power to differentiate compound permeabilities were
      evident with HCE-T cells, and were even more pronounced in the case of C-HCE,
      corresponding very well with data from ERCs and EHCs. A net secretion of
      rhodamine 123 was not observed with any of the models, suggesting that P
      glycoprotein or similar efflux systems have no significant effects on corneal
      permeability. Currently available corneal epithelial cell culture systems show
      differences in epithelial barrier function. Systems lacking functional cell-cell
      contacts are of limited value for assessing corneal permeability, and should be
      critically evaluated for other purposes.

PMID- 18333714
TI  - Integrated decision-tree testing strategies for acute systemic toxicity and
      toxicokinetics with respect to the requirements of the EU REACH legislation.
AB  - Liverpool John Moores University and FRAME conducted a joint research project,
      sponsored by Defra, on the status of alternatives to animal testing with regard
      to the European Union REACH (Registration, Evaluation and Authorisation of
      Chemicals) system for the safety testing and risk assessment of chemicals. The
      project covered all the main toxicity endpoints associated with REACH. This paper
      focuses on the use of alternative (non-animal) methods (both in vitro and in
      silico) for acute systemic toxicity and toxicokinetic testing. The paper reviews
      in vitro tests based on basal cytotoxicity and target organ toxicity, along with
      QSAR models and expert systems available for this endpoint. The use of PBPK
      modelling for the prediction of ADME properties is also discussed. These tests
      are then incorporated into a decision-tree style, integrated testing strategy,
      which also includes the use of refined in vivo acute toxicity tests, as a last
      resort. The implementation of the strategy is intended to minimise the use of
      animals in the testing of acute systemic toxicity and toxicokinetics, whilst
      satisfying the scientific and logistical demands of the EU REACH legislation.

PMID- 18333715
TI  - Integrated decision-tree testing strategies for developmental and reproductive
      toxicity with respect to the requirements of the EU REACH legislation.
AB  - Liverpool John Moores University and FRAME conducted a research project,
      sponsored by Defra, on the status of alternatives to animal testing with regard
      to the European Union REACH (Registration, Evaluation and Authorisation of
      Chemicals) system for the safety testing and risk assessment of chemicals. The
      project covered all the main toxicity endpoints associated with the REACH system.
      This paper focuses on the prospects for the use of alternative methods (both in
      vitro and in silico) in developmental and reproductive toxicity testing. It
      considers many tests based on primary cells and cell lines, and the available
      expert systems and QSARs for developmental and reproductive toxicity, and also
      covers tests for endocrine disruption. Ways in which reduction and refinement
      measures can be used are also discussed, particularly the use of an enhanced one
      generation reproductive study, which could potentially replace the two-generation
      study, and therefore considerably reduce the number of animals required in
      reproductive toxicity. Decision-tree style integrated testing strategies are also
      proposed for developmental and reproductive toxicity and for endocrine
      disruption, followed by a number of recommendations for the future facilitation
      of developmental and reproductive toxicity testing, with respect to human risk
      assessment.

PMID- 18333716
TI  - An integrated decision-tree testing strategy for eye irritation with respect to
      the requirements of the EU REACH legislation.
AB  - This paper presents some results of a joint research project, sponsored by Defra
      and conducted by FRAME and Liverpool John Moores University, on the status of
      alternatives to animal testing with regard to the European Union REACH
      (Registration, Evaluation and Authorisation of Chemicals) system for the safety
      testing and risk assessment of chemicals. The project covered all the main
      toxicity endpoints associated with REACH. This paper focuses on the use of
      alternative (non-animal) methods (both in vitro and in silico) for eye irritation
      testing. The manuscript reviews numerous in vitro tests and their possible
      collation into test batteries, in silico models and a refined in vivo method (the
      low volume eye test), before combining the use of all these methods into an
      integrated testing strategy. The aim of this strategy is a reduction in the
      number animal tests which would need to be performed in the process of fulfilling
      the REACH system criteria; this would also lead to a lowering of the number of
      animals required in compliance with the REACH system requirements.

PMID- 18333717
TI  - An integrated decision-tree testing strategy for repeat dose toxicity with
      respect to the requirements of the EU REACH legislation.
AB  - This paper presents some results of a joint research project conducted by FRAME
      and Liverpool John Moores University, and sponsored by Defra, on the status of
      alternatives to animal testing with regard to the European Union REACH
      (Registration, Evaluation and Authorisation of Chemicals) system for the safety
      testing and risk assessment of chemicals. The project covered all the main
      toxicity endpoints associated with REACH. This paper focuses on the use of
      alternative (non-animal) methods (both in vitro and in silico) for repeat dose
      (sub-acute, sub-chronic and chronic) toxicity testing. It reviews the limited
      number of in silico and in vitro tests available for this endpoint, and outlines
      new technologies which could be used in the future, e.g. the use of biomarkers
      and the 'omics' technologies. An integrated testing strategy is proposed, which
      makes use of as much non-animal data as possible, before any essential in vivo
      studies are performed. Although none of the non-animal tests are currently
      undergoing validation, their results could help to reduce the number of animals
      required for testing for repeat dose toxicity.

PMID- 18333718
TI  - Ecotoxicity testing: science, politics and ethics.
AB  - Animal welfare organisations have long been concerned about the use of animals
      for ecotoxicity testing. Ecotoxicity testing is a necessary part of the statutory
      risk assessment of chemicals that may be released into the environment. It is
      sometimes also carried out during the development of new chemicals and in the
      investigation of pollution in the field. This review considers the existing
      requirements for ecotoxicity testing, with particular reference to practices in
      the European Union, including the recent REACH system proposals, before
      discussing criticisms that have been made of existing practices for environmental
      risk assessment. These criticisms have been made on scientific and ethical
      grounds, as well as on questions of cost. A case is made for greater investment
      in the development of alternative testing methods, which could improve the
      science, as well as serving the cause of animal welfare. It has frequently been
      suggested that the statutory requirements for environmental risk assessment are
      too rigid and bureaucratic. A case is made for flexibility and the greater
      involvement of scientists in the risk assessment procedure, in the interests of
      both improved science and improved animal welfare.

PMID- 18333720
TI  - Dignity.

PMID- 18333722
TI  - Hospital care at the end of life: the effect of health insurance type on duration
      of a terminal hospitalization.

PMID- 18333723
TI  - The paraprofessional's role in breaking bad news.

PMID- 18333724
TI  - Culture and financing influence palliative care services, study populations, and
      generalizability of research findings.

PMID- 18333725
TI  - Cost of hospice care.

PMID- 18333726
TI  - Regional foundations offer third way to underwrite palliative care development.

PMID- 18333727
TI  - Advance care planning among the oldest old.
AB  - OBJECTIVES: To describe end-of-life advance care planning among the oldest-old
      (those >/= 85 years) and to identify patient characteristics and healthcare
      utilization patterns associated with likelihood of care planning documentation.
      DESIGN: Medical charts were abstracted for evidence of advance care planning
      documentation (including surrogate for health care decisions) and linked to
      patient demographic, clinical, and health utilization characteristics. SETTING:
      Veterans Affairs Greater Los Angeles Healthcare System (VA GLAHS). PARTICIPANTS:
      All Veterans (n = 175) aged >/= 85 who died between September 1999 and October
      2000 and used services at the VA GLAHS in the last year of life. MEASUREMENTS:
      The association of patient demographic, clinical, and health care utilization
      characteristics with documentation of advance care planning and surrogates was
      modeled using multivariate logistic regression. RESULTS: Among veterans (mean age
      at death, 89.4 +/- 3.8 years), 50 of 149 (34%) electronic available records had
      documented care preferences whereas 68 (46%) had documentation of surrogates.
      Considering demographic, clinical, and service use characteristics, only age
      (adjusted odds ratio [AOR]: 1.1 per year; 95% confidence interval [CI]: 1.0-1.2)
      and outpatient visits (AOR: 1.6 per quartile of general and geriatric medicine
      visit frequency; 95% CI: 1.1-;2.3) were associated with advance directive
      completion. A multivariable regression model using the same predictors to predict
      documentation of surrogates found similar associations with total outpatient
      visits (AOR: 1.5; 95% CI: 1.0-2.0) and general and geriatric medicine
      utilization. (AOR: 1.4; 95% CI: 1.0-2.0). CONCLUSION: Even in a health care
      system known for high-quality chronic illness care, documentation of advance care
      planning and selected proxies for health care decisions at the end of life was
      infrequent. Outpatient primary care and geriatric providers' visits were more
      frequent among those who had documented advance care planning, suggesting that
      involvement of these practitioners may improve end-of-life care.

PMID- 18333728
TI  - Psychiatric issues in palliative care: recognition of depression in patients
      enrolled in hospice care.
AB  - Major depression is prevalent, difficult to assess, underrecognized, and
      undertreated in hospice settings. Furthermore, it is associated with significant
      morbidity and mortality. A retrospective chart review of 2716 patients receiving
      hospice care was conducted in order to determine the baseline rate of recognition
      of depression in patients with advanced, life-threatening illnesses by frontline
      hospice clinicians. Documentation of "depression" as either a diagnosis or
      problem was used as an estimate of how often these disorders were considered
      significant issues by the treating interdisciplinary team. Of the patients
      receiving home/long-term care, 10.8% (234/2168) had depression documented as a
      diagnosis or significant problem. The presence of recognized depression in this
      setting was associated with significant differences in gender, marital status,
      and terminal diagnoses. Total length of hospice care was also significantly
      longer. Of patients receiving inpatient care, 13.7% (75/548) had depression
      documented as a diagnosis or significant problem. Recognized depression in this
      setting was associated with significant differences in marital status, length of
      inpatient stay, and total time in hospice care. If documentation is
      representative of the care that the interdisciplinary teams provide, depression
      of any kind appears to be underrecognized in this population. In fact, it is on
      the low end of prevalence estimates in the literature. Improved depression
      assessment is needed in order to minimize the impact of depression on patients
      living with advanced, life-threatening illnesses.

PMID- 18333729
TI  - Introduction of a pediatric palliative care curriculum for pediatric residents.
AB  - INTRODUCTION: The Pediatric Palliative Care Curriculum (PPCC) was introduced as a
      pilot study in response to the published need for increased pediatric education
      in end-of-life (EOL) care. The PPCC was designed to better train residents in EOL
      issues so they could become more comfortable and knowledgeable in caring for
      children and adolescents with life-threatening illnesses. METHOD: The PPCC
      consisted of six hour-long sessions run by a clinical psychologist, a licensed
      social worker, and faculty with experience in EOL care. The curriculum repeated
      every 6 weeks for 1 year. Residents in the training program at Stanford
      University rotating through oncology, pulmonology, and pediatric intensive care
      unit (PICU) were invited to attend. Session topics included: (1) personal coping
      skills, (2) being a caring professional, (3) recognizing cultural and familial
      differences, (4) pain management, (5) practical issues, and (6) meeting a
      bereaved parent. Pretest and posttest surveys with five-point Likert scale
      questions were used to measure curricular impact. RESULTS: Statistically
      significant improvement was found in resident self-report of: feeling prepared to
      initiate do-not-resuscitate discussions (p </= 0.001), access to nonpharmacologic
      pain resources (p </= 0.005), exposure to role models who balance medical
      professionalism and expression of grief (p </= 0.005), ability to address dying
      patient anxiety (p </= 0.01), administer pain medications (p </= 0.01), initiate
      organ donation discussions (p </= 0.05), and discuss transition from curative to
      palliative care (p </= 0.05). Survey ratings for the following topics were
      unchanged: "expression of grief is unprofessional" and "residency stress
      prohibits the processing of and coping with grief." CONCLUSIONS: Pediatric
      residents who participated in this pilot study felt they learned important skills
      in pediatric EOL care and enhanced their confidence in their ability to care for
      dying patients and their families. Interventions like the PPCC may be useful at
      other institutions and aid in the transition to competency-based training.

PMID- 18333730
TI  - Growing pains: health care enters "team"-age.

PMID- 18333731
TI  - Building the field of cancer pain.

PMID- 18333732
TI  - Impact of an inpatient palliative care team: a randomized control trial.
AB  - BACKGROUND: Palliative care improves care and reduces costs for hospitalized
      patients with life-limiting illnesses. There have been no multicenter randomized
      trials examining impact on patient satisfaction, clinical outcomes, and
      subsequent health care costs. OBJECTIVE: Measure the impact of an
      interdisciplinary palliative care service (IPCS) on patient satisfaction,
      clinical outcomes, and cost of care for 6 months posthospital discharge. METHODS:
      Multicenter, randomized, controlled trial. IPCS provided consultative,
      interdisciplinary, palliative care to intervention patients. Controls received
      usual hospital care (UC). SETTING AND SAMPLE: Five hundred seventeen patients
      with life-limiting illnesses from a hospital in Denver, Portland, and San
      Francisco enrolled June 2002 to December 2003. MEASURES: Modified City of Hope
      Patient Questionnaire, total health care costs, hospice utilization, and
      survival. RESULTS: IPCS reported higher scores for the Care Experience scale
      (IPCS: 6.9 versus UC: 6.6, p = 0.04) and for the Doctors, Nurses/Other Care
      Providers Communication scale (IPCS: 8.3 versus UC: 7.5, p = 0.0004). IPCS
      patients had fewer intensive care admissions (ICU) on hospital readmission (12
      versus 21, p = 0.04), and lower 6-month net cost savings of $4,855 per patient (p
      = 0.001). IPCS had longer median hospice stays (24 days versus 12 days, p =
      0.04). There were no differences in survival or symptom control. CONCLUSIONS:
      IPCS patients reported greater satisfaction with their care experience and
      providers' communication, had fewer ICU admissions on readmission, and lower
      total health care costs following hospital discharge.

PMID- 18333733
TI  - Clinical findings of a palliative care consultation team at a comprehensive
      cancer center.
AB  - BACKGROUND: Palliative care consultation teams (PCCTs) are being established in
      cancer centers for the management of patients' physical and psychosocial
      distress. As clinical findings of these teams have been reported infrequently, we
      aim to describe the experience of our high-volume inpatient PCCT. PATIENTS AND
      METHODS: We obtained clinical and demographic data on patients referred to our
      PCCT from the palliative care departmental database from September 1, 2003, to
      August 31, 2004. RESULTS: In 1 year, 1067 consultations took place for 922
      hospitalized patients. The patients' mean age was 60 (range, 3-98) years. The
      most common cancers were thoracic/head and neck, gastrointestinal, genitourinary,
      gynecologic cancers, and lymphoma. Thirty-four percent of the patients were
      transferred to the inpatient palliative care unit, while the remainder were
      followed by the PCCT as consultants. The main problems requiring PCCT
      consultation were pain (56%), delirium (34%), dyspnea (25%), fatigue (14%), and
      end-of-life psychosocial (EOL) issues (12%). Twenty-four percent of patients died
      during the hospitalization. Death during the hospitalization was more common in
      patients with delirium, dyspnea, and EOL issues and less likely in patients
      referred to the PCCT for pain or depression. Constipation was more common in
      patients with solid tumors, whereas EOL issues were more common in patients with
      hematologic malignancies. Of the patients who were able to be discharged, 56%
      went home, 37% to hospice, and 7% elsewhere. CONCLUSIONS: These results provide
      insight into the demand and utility of this service for those considering the
      establishment of a PCCT.

PMID- 18333734
TI  - End-of-life care in adults with cystic fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) is a life-limiting congenital disease, with most
      patients dying at a young age of progressive lung disease. Lung transplantation
      offers hope for many but may not occur. There is little to guide the provision of
      palliative care to this young population who maintain hope in the possibility of
      lung transplantation. METHODS: To inform the development of an appropriate model
      of palliative care, a medical record review of CF patients dying within a 5-year
      period without lung transplantation was undertaken. The aspects of care that were
      preventative, therapeutic, or palliative were quantified. RESULTS: Of the 20
      records studied, all died in hospital. Only 15% of patients had a do-not
      resuscitate order agreed to more than 1 week prior to death, increasing to 90% at
      the time of death (median of 2 days before death). Opioids were prescribed for 1
      patient (5%) at 1 week prior to death, increasing to 85% of patients in the last
      24 hours of life (median of 36 hours before death). During the last 24 hours of
      life, intravenous antibiotics continued in 85%, and assisted ventilation in 90%
      of subjects. CONCLUSION: We conclude that the circumstances surrounding the death
      of patients with CF holds challenges for their effective palliative care. CF
      patients continue life prolonging and preventative treatments until the last
      hours of life. There is an urgent need to examine palliative care approaches that
      may usefully coexist with maintaining transplantation options in the end-of-life
      care of this population.

PMID- 18333735
TI  - Is there a higher risk of respiratory depression in opioid-naive palliative care
      patients during symptomatic therapy of dyspnea with strong opioids?
AB  - OBJECTIVE: Dyspnea is a highly prevalent symptom in palliative care patients.
      Opioids are the first-line therapy for symptomatic relief of dyspnea. However,
      respiratory depression is still a feared side effect of therapy with WHO III
      opioids. The risk of respiratory depression in opioid-naive patients and in
      patients pretreated with strong opioids during symptomatic therapy of dyspnea was
      investigated in palliative care patients. PATIENTS AND METHODS: Twenty-seven
      patients were included in a prospective, nonrandomized study. All patients
      suffered from moderate to severe dyspnea. Transcutaneous measurement (earlobe
      sensor) of carbon dioxide partial pressure (tcpaCO(2)), pulse oximetry oxygen
      saturation (SaO(2)), and pulse frequency (PF) were monitored with SenTec Digital
      Monitor (SenTec AG, Therwill, CH). The following monitoring data were compared:
      baseline recording for 15 minutes, and 30, 60, 90, and 120 minutes after opioid
      application. RESULTS: The data obtained with transcutaneous measurement showed
      that there were no significant differences between the groups of opioid-naive
      patients and those pretreated with strong opioids with regard to tcpaCO(2)
      increase or SaO(2) decrease after the first opioid application. Neither SaO(2)
      decreased significantly nor tcpaCO(2) increased significantly after the initial
      opioid application, which means there was no opioid-induced respiratory
      depression. The first opioid application, however, resulted in a significant
      decrease in the intensity of dyspnea and respiratory rate. CONCLUSIONS: No higher
      risk of respiratory depression and increase in tcpaCO2 in opioid-naive palliative
      care patients, compared to patients pretreated with strong opioids, during
      symptomatic therapy of dyspnea with strong opioids could be found.

PMID- 18333736
TI  - Improving end-of-life outcomes in nursing homes by targeting residents at high
      risk of mortality for palliative care: program description and evaluation.
AB  - OBJECTIVES: The objectives were (1) to describe the Making Advance Planning a
      Priority (MAPP) program, a program designed to identify nursing home (NH)
      residents at high risk of death and (2) to evaluate end-of-life care outcomes for
      NH residents at high risk of death. DESIGN: PROGRAM DESCRIPTION and evaluation
      using a retrospective chart review before and after implementation of the MAPP
      program. PARTICIPANTS: NH residents who died 1 year before program implementation
      compared to NH residents who died 1 year after program implementation (n = 72).
      PROGRAM DESCRIPTION: The MAPP program was designed to: (1) identify residents at
      high risk of death, (2) inform the attending physician of the residents'
      mortality risk, (3) obtain palliative care or, if the prognosis was 6 months of
      less, a hospice consultation, and (4) improve advance care planning
      documentation. PROGRAM EVALUATION: Site of death (hospital versus nursing home),
      presence of an advance directive, presence of an order for cardiopulmonary
      resuscitation, proportion of NH residents with palliative care and/or hospice
      consultation prior to death, length of palliative care and/or hospice services
      before death. Following implementation of the MAPP program, we hypothesized that
      there would be a reduction in hospitalizations, an increase in hospice/palliative
      care referrals, an increase hospice/palliative care length of service, an
      increase the utilization of advance directives, but no difference in days in the
      hospital before death. RESULTS: Following implementation of the MAPP program
      intervention, residents were less likely to die in the hospital (48.2%
      preintervention versus 8.9% postintervention, p < 0.0001). Every resident who
      died after implementation of the MAPP program had an advanced directive (p =
      0.03). Residents were more also more likely to get palliative care referrals
      (7.4% preintervention versus 31.1% postintervention, p = 0.02). CONCLUSION: An
      intervention designed to address the end-of-life needs of NH residents at high
      risk of death improves end-of-life outcomes with a reduction in terminal
      hospitalizations, an increase in palliative care referrals and improvement of
      advance directive completion.

PMID- 18333738
TI  - Criminal prosecutions of physicians providing palliative or end-of-life care.
AB  - Although medical malpractice suits commonly occur in medical practice, few
      physicians experienced criminal prosecution related to adverse clinical outcomes
      before 1990. Criminal prosecutions of physicians increased in frequency early in
      that decade, however, including a handful of cases involving palliative or end-of
      life care. Reviews published around the end of the 1990s examined those
      prosecutions, listing causative factors and offering recommendations to prevent
      further cases. In this paper, we provide an updated review of criminal
      prosecutions of physicians providing palliative or end-of-life care, presenting
      three cases that occurred after 1998. We summarize these newer cases'
      chronologies and outcomes, comparing them to cases described in past reviews. Our
      analysis suggests that important factors not described in earlier reviews,
      especially conflicting views of the standard of care in hospice and palliative
      medicine, contributed to the development of these prosecutions.

PMID- 18333737
TI  - Determinants of do-not-resuscitate orders in palliative home care.
AB  - OVERVIEW: Do-not-resuscitate (DNR) orders allow home care clients to communicate
      their own wishes over medical treatment decisions, helping to preserve their
      dignity and autonomy. To date, little is known about DNR orders in palliative
      home care. Basic research to identify rates of completion and determinants of DNR
      orders has yet to be examined in palliative home care. PURPOSE: The purpose of
      this exploratory study was to determine who in palliative home care has a DNR
      order as part of their advance directive. METHODS: Information on health was
      collected using the interRAI instrument for palliative care (interRAI PC). The
      sample included 470 home care clients from one community care access centre in
      Ontario. RESULTS: This study indicated that a preference to die at home (odds
      ratio [OR]: 8.29, confidence interval [CI]: 4.55-15.11); close proximity to death
      (OR: 0.99, CI: 0.99-1.00); daily incontinence (OR: 2.74, CI: 1.05-7.16); and
      sleep problems (OR: 1.85, CI: 1.02-3.37) are associated with DNR orders. In
      addition, clients who are more accepting of their situation are 5.67 times (CI:
      1.67-19.27) more likely to have a DNR in place. CONCLUSION: This study represents
      an important first step to identifying issues related to DNR orders. In addition
      to proximity to death, incontinence, and sleep problems, acceptance of one's own
      situation and a preference to die at home are important determinants of DNR
      completion. The results imply that these discussions might often depend not only
      on the health of the clients but also on the clients' acceptance of their current
      situation and where they wish to die.

PMID- 18333739
TI  - Grief in children and developmental concepts of death #138.

PMID- 18333740
TI  - Advance care planning in chronic illness #162.

PMID- 18333741
TI  - The consolations of faith: a meditation on the power of religious faith.

PMID- 18333742
TI  - A "bien" experience.

PMID- 18333743
TI  - Trial of angioembolization of advanced stage tumors feeding arteries exemplifying
      aggressive and active interventional palliation.

PMID- 18333754
TI  - ALK1 opposes ALK5/Smad3 signaling and expression of extracellular matrix
      components in human chondrocytes.
AB  - INTRODUCTION: TGF-beta is a multifunctional regulator of chondrocyte
      proliferation, differentiation, and extracellular matrix production.
      Dysregulation of TGF-beta action has been implicated in cartilage diseases such
      as osteoarthritis. TGF-beta signaling is transduced through a pair of
      transmembrane serine/threonine kinases, known as the type I (ALK5) and type II
      receptors. However, recent studies on endothelial cells have identified ALK1 as a
      second type I TGF-beta receptor and have shown that ALK1 and ALK5 have opposing
      functions in these cells. Here we examined ALK1 expression and its regulation of
      TGF-beta signaling and responses in human chondrocytes. MATERIALS AND METHODS:
      ALK1 expression in human chondrocytes was examined by RT-PCR and Western blot.
      The ability of ALK1 to form complexes with other TGF-beta receptors was
      determined by affinity labeling/immunoprecipitation and by immunoprecipitation
      followed by Western blot. The effect of ALK1 on TGF-beta1-induced signaling and
      responses was determined by varying ALK1 expression levels and measuring
      transcriptional activity using promoter/luciferase assays, Smad1/5 and Smad3
      phosphorylation, and expression of type II collagen, PAI-1, and fibronectin.
      RESULTS: Our results indicate that ALK1 is expressed in human chondrocytes and
      that it is a component of the TGF-beta receptor system, associating with ALK5,
      type II TGF-beta receptor, endoglin, and betaglycan. Furthermore, we show that
      both ALK1 and ALK5 are needed for TGF-beta-induced phosphorylation of
      intracellular mediators Smad1/5, whereas only ALK5 is essential for TGF-beta1
      induced phosphorylation of Smad3. In addition, our results show that ALK1
      inhibits, whereas ALK5 potentiates, TGF-beta-induced Smad3-driven transcriptional
      activity and the expression of PAI-1, fibronectin, and type II collagen in
      chondrocytes. CONCLUSIONS: Our results suggest that ALK1 and ALK5 display
      opposing functions in human chondrocytes, implicating an essential role for ALK1
      in the regulation of TGF-beta signaling and function in these cells.

PMID- 18333755
TI  - Integrin-mediated expression of bone formation-related genes in osteoblast-like
      cells in response to fluid shear stress: roles of extracellular matrix, Shc, and
      mitogen-activated protein kinase.
AB  - Integrins play significant roles in mechanical responses of cells on
      extracellular matrix (ECM). We studied the roles of integrins and ECM proteins
      (fibronectin [FN], type I collagen [COL1], and laminin [LM]) in shear-mediated
      signaling and the expression of bone formation-related genes (early growth
      response-1 [Egr-1], c-fos, cyclooxygenase-2 [Cox-2], and osteopontin [OPN]) in
      human osteosarcoma MG63 cells. MG63 cells on FN, COL1, and LM were kept as
      controls or subjected to shear stress (12 dynes/cm(2)), and the association of
      alpha(v)beta(3) and beta(1) integrins with Shc, phosphorylation of mitogen
      activated protein kinases (MAPKs, i.e., extracellular signal-regulated kinase
      [ERK], c-jun-NH(2)-terminal kinase [JNK], and p38), and expressions of Egr-1, c
      fos, Cox-2, and OPN were determined. In MG63 cells, shear stress induces
      sustained associations of alpha(v)beta(3) and beta(1) with Shc when seeded on FN,
      but sustained associations of only beta(1) with Shc when seeded on COL1/LM. Shear
      inductions of MAPKs and bone formation-related genes were sustained (24 h) in
      cells on FN, but some of these responses were transient in cells on COL1/LM. The
      shear activations of ERK, JNK, and p38 were mediated by integrins and Shc, and
      these pathways differentially modulated the downstream bone formation-related
      gene expression. Our findings showed that beta(1) integrin plays predominant
      roles for shear-induced signaling and gene expression in osteoblast-like MG63
      cells on FN, COL1, and LM and that alpha(v)beta(3) also plays significant roles
      for such responses in cells on FN. The beta(1)/Shc association leads to the
      activation of ERK, which is critical for shear induction of bone formation
      related genes in osteoblast-like cells.

PMID- 18333756
TI  - Statistics of random protein superpositions: p-values for pairwise structure
      alignment.
AB  - Quantification of statistical significance is essential for the interpretation of
      protein structural similarity. To address this, a random model for protein
      structure comparison was developed. Novelty of the model is threefold. First, a
      sample of random structure comparisons is restricted to molecules of the same
      size and shape as the superposition of interest. Second, careful selection of the
      sample and accurate modeling of shape allows approximation of the root mean
      square deviation (RMSD) distribution of random comparisons with a Nakagami
      probability density function. Third, through convolution, a second probability
      density function is obtained that describes the coordinate difference vector
      projections underlying the random distribution of RMSD. This last feature allows
      sampling random distributions of not only RMSD, but also any similarity score
      that depends on difference vector projections, such as GDT_TS score, TM score,
      and LiveBench 3D score. Probabilities estimated from the method correlate well
      with common measures of structural similarity, such as the Dali Z-score and the
      GDT_TS score. As a result, the p-value for a given superposition can be
      calculated using simple formulae depending on RMSD, radius of gyration, and
      thinnest molecular dimension. In addition to scoring structural similarity, p
      values computed by this method can be applied to evaluation of homology modeling
      techniques, providing a statistically sound alternative to scores used in
      reference-independent evaluation of alignment quality.

PMID- 18333757
TI  - Computational modeling of post-transcriptional gene regulation by microRNAs.
AB  - MicroRNAs (miRNAs) have recently emerged as a new complex layer of gene
      regulation. MiRNAs act post-transcriptionally, influencing the stability,
      compartmentalization, and translation of their target mRNAs. Computational
      efforts to understand the post-transcriptional gene regulation by miRNAs have
      been focused on the target prediction tools, while quantitative kinetic models of
      gene regulation by miRNAs have so far largely been overlooked. We here develop a
      kinetic model of post-transcriptional gene regulation by miRNAs, focusing on the
      miRNAs' effect on increasing the target mRNAs degradation rates. The model is
      fitted to a temporal microarray dataset where human mRNAs are measured upon
      transfection with a specific miRNA (miRNA124a). The proposed model exhibits good
      fit with many target mRNA profiles, indicating that such type of models can be
      used for studying post-transcriptional gene regulation by miRNA. In particular,
      the proposed kinetic model can be used for quantifying the miRNA-mediated effects
      on its targets in the miRNA mis-expression experiments. The model makes an
      experimentally verifiable prediction of the miRNA124a decay rate, quantifies the
      miRNA-mediated effect on the target mRNAs degradation, and yields a good
      correspondence between the inferred and experimentally measured decay rates of
      human target mRNAs.

PMID- 18333758
TI  - New method for the assessment of all drug-like pockets across a structural
      genome.
AB  - With the increasing wealth of structural information available for human
      pathogens, it is now becoming possible to leverage that information to aid in
      rational selection of targets for inhibitor discovery. We present a methodology
      for assessing the drugability of all small-molecule binding pockets in a
      pathogen. Our approach incorporates accurate pocket identification, sequence
      conservation with a similar organism, sequence conservation with the host, and
      structure resolution. This novel method is applied to 21 structures from the
      malarial parasite Plasmodium falciparum. Based on our survey of the structural
      genome, we selected enoyl-acyl carrier protein reductase (ENR) as a promising
      candidate for virtual screening based inhibitor discovery.

PMID- 18333759
TI  - Computation-based discovery of cis-regulatory modules by hidden Markov model.
AB  - A key component in genome sequence analysis is the identification of regions of
      the genome that contain regulatory information. In higher eukaryotes, this
      information is organized into modular units called cis-regulatory modules. Each
      module contains multiple binding sites for a specific combination of several
      transcription factors. In this article, we propose a hidden Markov model (HMM) to
      identify transcription factor binding sites (TFBSs) and cis-regulatory modules
      (CRMs). For a given genomic sequence, we first select potential TFBSs from a
      large database (e.g., TRANSFAC), then construct an HMM where the TFBSs are only
      counted when they occur within a specialized CRM state. The novel features of the
      proposed method include that it does not assume a small set of TFBSs for a given
      gene; on the other hand, the method utilizes information from a large collection
      of well-characterized TFBSs and therefore is computationally more efficient and
      robust than the de novo methods. Our approach is applied to three data sets with
      experimentally evaluated TFBSs. The method shows better specificity and
      sensitivity than other similar computational tools in identifying CRMs and TFBSs.
      The executable codes of our programs and module predictions across the fly
      Drosophila genome are available at www.stat.purdue.edu/~ jingwu/module/.

PMID- 18333760
TI  - Determining nucleolar association from sequence by leveraging protein-protein
      interactions.
AB  - Controlled intra-nuclear organization of proteins is critical for sustaining
      correct function of the cell. Proteins and RNA are transported by passive
      diffusion and associate with compartments by virtue of diverse molecular
      interactions--presenting a challenging problem for data-driven model building. An
      increasing inventory of proteins with known intra-nuclear destination and
      proliferation of molecular interaction data motivate an integrative method,
      leveraging the existing evidence to build accurate models of intranuclear
      trafficking. Kernel canonical correlation analysis (KCCA) enables the
      construction of predictors based on genomic sequence data, but leverages other
      knowledge sources during training. The approach specifically involves the
      induction of protein sequence features and relations most pertinent to the
      recovery of nucleolar associated protein-protein interactions. With success rates
      of about 78%, the classification of nucleolar association from KCCA-induced
      features surpasses that of baseline approaches. We observe that the coalescence
      of protein-protein interaction data with sequence data enhances the prediction of
      highly interconnected, key ribosomal and RNA-related nucleolar proteins. For
      supplementary material, see www.itee.uq.edu.au/~ pprowler/nucleoli.

PMID- 18333761
TI  - Mitochondrial disorders in the nervous system.
AB  - Mitochondrial diseases (encephalomyopathies) have traditionally been ascribed to
      defects of the respiratory chain, which has helped researchers explain their
      genetic and clinical complexity. However, other mitochondrial functions are
      greatly important for the nervous system, including protein importation,
      organellar dynamics, and programmed cell death. Defects in genes controlling
      these functions are attracting increasing attention as causes not only of
      neurological (and psychiatric) diseases but also of age-related neurodegenerative
      disorders. After discussing some pathogenic conundrums regarding the neurological
      manifestations of the respiratory chain defects, we review altered mitochondrial
      dynamics in the etiology of specific neurological diseases and in the
      physiopathology of more common neurodegenerative disorders.

PMID- 18333762
TI  - Co-sleeping and breastfeeding: is it safe?

PMID- 18333763
TI  - Comparison of manual and electric breast pumps among WIC women returning to work
      or school in Hawaii.
AB  - INTRODUCTION: The Women, Infants, and Children (WIC) branch of the Hawaii
      Department of Health encourages and assists mothers in breastfeeding. A study was
      done to determine whether an electric breast pump (vs. a manual pump) would
      increase breastfeeding duration in those returning to work or school full-time.
      MATERIALS AND METHODS: During 2002-2003, a randomized trial was conducted among
      280 women, with the duration of breastfeeding analyzed in 229 of these women.
      Descriptive analyses and a multivariate logistic regression analysis assessed
      factors associated with breastfeeding at 6 months. Unadjusted and adjusted
      survival analyses were performed to estimate the duration of breastfeeding.
      RESULTS: In all, 76.8% of women using the manual breast pump and 72.3% of those
      using the electric breast pump breastfed for at least 6 months. This difference
      did not reach statistical significance. In the survival analysis adjusted for
      pump assignment, maternal age, race/ethnicity, marital status, and parity, women
      with at least some college education breastfed for a 38% shorter time than women
      with a high school or lower education. CONCLUSIONS: Our findings suggest that the
      manual breast pump may work as well as the electric breast pump when
      breastfeeding is encouraged and supported among women returning to work or school
      full-time. Particular attention should be given to examining reasons why women
      with greater education breastfed for a shorter duration. Further research is
      needed to validate these results to better inform breastfeeding women returning
      to work or school.

PMID- 18333764
TI  - Importance of vacuum for breastmilk expression.
AB  - OBJECTIVE: To determine the effect of the strength of applied vacuum on the flow
      rate and yield of breastmilk using an electric breast pump. STUDY DESIGN: Twenty
      one breastfeeding mothers and two expressing mothers expressed their breastmilk
      for 15 minutes using an electric breast pump set at their own maximum comfortable
      vacuum, and at one to three softer vacuums. Milk yield and flow rate were
      measured. RESULTS: At the maximum comfortable vacuum (-190.7 +/- 8.8 mm Hg) 4.3
      +/- 0.4 milk ejections occurred during 15 minutes of expression and yielded 118.5
      +/- 11.4 mL of milk (65.5 +/- 4.1% of the available milk). Softer vacuums yielded
      less milk volume (p < 0.05) and less of the available milk (p < 0.01). Milk flow
      rate was greater during the first milk ejection than the third or subsequent milk
      ejections (p < 0.001). Cream content of the milk was highest after expressing for
      15 minutes using the mother's maximum comfortable vacuum. CONCLUSIONS: Use of the
      mother's maximum comfortable vacuum enhances milk flow rate and milk yield. The
      cream content of the milk at the end of the expression period was an indicator of
      how effectively the breast had been drained.

PMID- 18333765
TI  - Birth order and breastfeeding initiation: results of a national survey.
AB  - BACKGROUND: Because of numerous health benefits for both mothers and babies,
      breastfeeding is the recommended method of infant feeding. We sought to determine
      the association between birth order and breastfeeding practices in families with
      multiple children. METHODS: The 2002 National Survey of Family Growth was used to
      analyze the demographic characteristics of a national probability sample of 2,115
      U.S. mothers aged 15 to 44 with two, three, four, and five or more children
      younger than age 19. In-person, computer-assisted interviews were conducted by
      trained female interviewers. The main variable of interest was birth order; the
      main outcome measure was breastfeeding initiation for each mother-child pair. We
      used multiple logistic regression models to determine the demographic predictors
      of breastfeeding the second child in families with two children. RESULTS: Mothers
      with two, three, four, and five or more children breastfed all of their children
      52.6%, 48.4%, 44.7%, and 57.1% of the time, respectively (p = 0.46). In families
      with multiple children, more than 70% of women made the same feeding choice for
      each of their children, whether it was breastfeeding or bottlefeeding. After
      controlling for demographic factors, Hispanic women and women with more than a
      high school education were significantly more likely to breastfeed their second
      child if they had breastfed the first child. CONCLUSION: U.S. mothers are likely
      to choose the same feeding method for each of their children, independent of the
      number of children they have. Breastfeeding promotion must take into
      consideration previous infant feeding experiences, if any.

PMID- 18333766
TI  - Physician-led outpatient breastfeeding medicine clinics in the United States.
AB  - Attrition of exclusive breastfeeding is highest during the first 3 months
      postpartum. Timely management of breastfeeding in the outpatient setting through
      innovative models of healthcare delivery may increase its duration and
      exclusivity. Our goal was to examine the structure and function of physician-led
      clinics in the United States that specialize in providing outpatient clinical
      support for breastfeeding-related issues ("breastfeeding medicine clinics"). We
      posted a survey on Listservs of the American Academy of Pediatrics, American
      Academy of Family Physicians, and Academy of Breastfeeding Medicine. The survey
      collected information on (1) clinic and physician demographics, (2) visit
      characteristics, (3) referral and reimbursement, (4) clinical activities, (5)
      continuing education resources, (6) teaching/education activities, and (7)
      advocacy activities, of physician-led outpatient breastfeeding medicine clinics.
      Lead physicians from 13 clinics responded to the survey. Their clinics provided
      clinical care for time-intensive breastfeeding problems. The clinics we described
      that were in existence longer than 2 years appeared to be economically
      sustainable. Most physicians who had provided specialized breastfeeding support
      for more than 5 years reported that their income was commensurate with others in
      their specialty. Most physicians who provided specialized breastfeeding medicine
      care additionally provided primary care services within the same clinical
      setting. Further research into fiscal and organizational aspects of establishing
      specialized physician-led breastfeeding clinics is needed. The potential of such
      clinics in contributing to collaborative practice-based research, as well as
      medical student and house staff education, needs to be explored.

PMID- 18333767
TI  - Methadone maintenance and long-term lactation.
AB  - Breastfeeding among methadone-maintained women is frequently challenged because
      of unclear guidelines regarding this practice. Previous research has confirmed
      that concentrations of methadone in breastmilk in the neonatal period are low.
      Currently unknown are the concentrations of methadone in breastmilk among women
      who breastfeed for longer periods of time. The purpose of this research is to
      examine concentrations of methadone in the plasma and breastmilk of women who
      breastfeed their infants beyond the neonatal period. Four methadone-maintained
      women provided blood and breastmilk samples up to 6 months postpartum. The
      concentrations of methadone in blood and breastmilk were low, contributing to the
      recommendation of breastfeeding for some methadone-maintained women.

PMID- 18333768
TI  - ABM clinical protocol #6: guideline on co-sleeping and breastfeeding. Revision,
      March 2008.

PMID- 18333769
TI  - ABM clinical protocol #18: use of antidepressants in nursing mothers.

PMID- 18333774
TI  - Engineered cardiac organoid chambers: toward a functional biological model
      ventricle.
AB  - A growing area in the field of tissue engineering is the development of tissue
      equivalents as model systems for in vitro experimentation and high-throughput
      screening applications. Although a variety of strategies have been developed to
      enhance the structure and function of engineered cardiac tissues, an inherent
      limitation with traditional myocardial patches is that they do not permit
      evaluation of the fundamental relationships between pressure and volume that
      characterize global contractile function of the heart. Therefore, in the
      following study we introduce fully biological, living engineered cardiac
      organoids, or simplified heart chambers, that beat spontaneously, develop
      pressure, eject fluid, contain residual stress, exhibit a functional Frank
      Starling mechanism, and generate positive stroke work. We also demonstrate
      regional variations in pump function following local cryoinjury, yielding a novel
      engineered tissue model of myocardial infarction. With the unique ability to
      directly evaluate relevant pressure-volume characteristics and regulate wall
      stress, this organoid chamber culture system provides a flexible platform for
      developing a controllable biomimetic cardiac niche environment that can be
      adapted for a variety of high-throughput and long-term investigations of cardiac
      pump function.

PMID- 18333775
TI  - Three-dimensional primary hepatocyte culture in synthetic self-assembling peptide
      hydrogel.
AB  - Drug metabolism studies and liver tissue engineering necessitate stable
      hepatocyte cultures that express liver functions for a minimum of 4 days to 3
      weeks. Current techniques, using different biomaterials and geometries, that
      maintain hepatocellular function in vitro exhibit a low cell density and
      functional capacity per unit volume. Herein we investigated a well-defined
      synthetic peptide that can self-assemble into three-dimensional interweaving
      nanofiber scaffolds to form a hydrogel, PuraMatrix, as a substrate for hepatocyte
      culture. Freshly isolated primary rat hepatocytes attached, migrated, and formed
      spheroids within 3 days after seeding on PuraMatrix. Hepatocytes expressed the
      apical membrane marker dipeptidyl peptidase IV at cell-cell contacts. Compared to
      the collagen sandwich, albumin and urea secretion on PuraMatrix were higher for
      the first week, and cytochrome P450IA1 activity was higher throughout the culture
      period. Mitochondrial membrane potential 1 day after seeding was higher on
      PuraMatrix than in the collagen sandwich, suggesting better preservation of the
      metabolic machinery. PuraMatrix and Matrigel showed similar albumin and urea
      production. PuraMatrix is an attractive system for generating hepatocyte
      spheroids that quickly restore liver functions after seeding. This system is also
      amenable to scale-up, which makes it suitable for in vitro toxicity, hepatocyte
      transplantation, and bioartificial liver development studies.

PMID- 18333776
TI  - Replacement of bone marrow by bone in rat femurs: the bone bioreactor.
AB  - During development and repair of bone, two distinct yet complementary mechanisms,
      intramembranous and endochondral, mediate new bone formation via osteoblasts.
      Because mechanical bone marrow ablation leads to the rapid and transient
      formation of new bone in the marrow cavity, we postulated that parathyroid
      hormone (PTH), which is a bone anabolic hormone, enhances the formation of new
      bone that forms after marrow ablation. We subjected the left femur of rats to
      mechanical marrow ablation, or sham operation, and injected the animals daily
      with PTH or vehicle for 1, 2, or 3 weeks in a first experiment, then with PTH,
      parathyroid hormone-related peptide (PTHrP), or vehicle for 3 weeks in a second
      experiment. We subjected both femurs from each rat to soft X-ray, peripheral
      quantitative computed tomography, computed tomography on a microscale, and
      histological analysis, and determined the concentration of serum osteocalcin. In
      addition, in the second experiment, we determined the serum concentration of
      calcium, tartrate-resistant acid phosphatase (TRAP), and receptor activator of NF
      kappaB ligand (RANKL) at 3 weeks, and subjected femurs to biomechanical testing.
      Following treatment with PTH or PTHrP for 3 weeks, bone filled the marrow cavity
      of the shafts whose marrow had been ablated. PTH increased trabecular density in
      the right femur, but failed to induce bone formation in the medullary region of
      the right unoperated femoral shafts. The newly formed bone endowed left femoral
      shafts with improved biomechanical properties when compared to those of right
      femurs and left femurs from control, sham-operated, and vehicle-treated rats.
      PTHrP, like PTH, increased serum osteocalcin, but neither increased serum
      calcium, TRAP, or RANKL at 3 weeks. Our results reveal that the newly formed bone
      that follows marrow ablation is responsive to PTH, expand the role of PTH in
      bone, and might open new avenues of investigations to the field of regenerative
      medicine and tissue engineering. Local bone marrow removal in conjunction with
      pharmacologic intervention with an anabolic agent might provide a technique for
      rapid preferential site-directed bone growth in areas of high bone loss.

PMID- 18333777
TI  - VEGF facilitates periosteal distraction-induced osteogenesis in rabbits: a micro
      computerized tomography study.
AB  - BACKGROUND AND PURPOSE: Distraction osteogenesis is routinely used for
      reconstruction of bone. Conversely, it was hypothesized that mechanical traction
      of the periosteum would induce bone formation, and hence the use of periosteal
      distraction for induction of osteogenesis has been proposed. Further, it was
      postulated that intracallus administration of vascular endothelial growth factor
      (VEGF) would facilitate osteogenesis. To investigate this hypothesis, formation
      of newly synthesized bone was evaluated using micro-computerized tomography
      (microCT) and histomorphometry. MATERIALS AND METHODS: Periosteal distractors
      were placed subperiosteally in one side of the mandible of rabbits, whereas the
      contralateral served as control. One group of animals received VEGF into the
      forming callus. Formation of bone was measured using microCT and histological
      analysis. RESULTS: The results demonstrate formation of new bone following
      periosteal distraction. Addition of VEGF to the distraction site increased bone
      synthesis. CONCLUSIONS: microCT and histological analysis validate the hypothesis
      that mechanical distraction of the periosteum induces osteogenesis and that VEGF
      has a positive effect on osteogenesis. Periosteal distraction is emerging as a
      reliable technique for bone regeneration.

PMID- 18333778
TI  - A novel approach to control growth, orientation, and shape of human osteoblasts.
AB  - Carbon-based materials are considered to be promising as implants because of
      their unique mechanical and biocompatibility properties. This article
      investigates the use of carbon-based materials as a functional interface for
      tissue scaffolds and medical implants. Three basic parameters were explored:
      graphene orientation, crystallinity, and surface interaction. These parameters
      were measured using optical microscopy, x-ray diffraction, and atomic force
      microscopy. To explore the effect of the orientation, samples were made with and
      without a preferred carbon orientation. Conversely, the crystallinity was studied
      using graphitic and carbonaceous matrices. Finally, the surface interaction study
      was carried out using oxygen surface functionalized and non-functionalized carbon
      fibers. Fluorescent, confocal, and environmental scanning microscopy were used to
      visualize cell response. The cell attachment, proliferation, and elongation were
      prevalent on the unidirectional carbon preform. Cells tended to orient parallel
      to the fiber axis (parallel to the 002 graphene plane) and proliferate as a
      function of higher crystallinity, although the addition of oxygen or other
      functional groups disrupted the interaction between cells and graphene surface
      and inhibited the growth. In conclusion, osteoblast (bone-forming cells)
      attachment and overall growth is a function of crystallite size, graphene
      orientation, and carbon graphitization.

PMID- 18333779
TI  - Tissue array substratum composed of histological sections: a new platform for
      orienting differentiation of embryonic stem cells towards hepatic lineage.
AB  - Culture technologies for differentiating embryonic stem cells (ESCs) into hepatic
      cells generally require some growth factors for several days. Here we present a
      new technology for efficiently differentiating mouse ESCs into hepatocyte-like
      cells in a supplement-free basal medium by using a tissue array substratum
      composed of histological sections. The substratum was prepared from liver tissues
      in various stages after administration of carbon tetrachloride to mice. The
      substrata derived from regenerating livers enhanced cell attachment, supported
      growth as clusters, and induced differentiation into cells expressing albumin,
      although the substrata from injured livers did not. In particular, the cells
      cultured on the most-proliferative regenerating liver-derived section substratum
      reconstructed the hepatic cord-like structures with bile canaliculus-like aspects
      in which some binucleated cells were involved, secreted albumin, and expressed
      cytochrome P450IA1 activity within a few days. This culture technology also
      provides a novel concept for Histomics, categorizing the features of different
      tissues based on the behavior of a cell line cultured on their array substratum
      (i.e., tissuome).

PMID- 18333780
TI  - In vivo development and long-term survival of engineered adipose tissue depend on
      in vitro precultivation strategy.
AB  - One strategy of adipose tissue engineering is to transplant adipocytes or
      adipocyte precursor cells in combination with polymeric materials. However, a
      satisfying formation of fat tissue and its long-term survival still remain major
      problems. There is increasing evidence that treatment of the cells prior to
      implantation plays a critical role in the success of adipose tissue growth. In a
      previous study, we established a model system based on 3T3-L1 cells that allows
      for reproducible engineering of mature, coherent adipose tissues in vitro. We
      utilized this model system in the current study and systematically investigated
      the long-term in vivo development of cellular constructs with varying stages of
      adipogenic development at the time point of implantation. Blank polyglycolic acid
      fiber meshes, scaffolds seeded with uninduced 3T3-L1 preadipocytes, and cell
      polymer constructs precultivated under adipogenic conditions for 2, 9, or 35 days
      were implanted subcutaneously into nude mice. Histological analysis revealed that
      no fat formation occurred in constructs without adipogenic precultivation.
      Implantation of mature fat pads (35 days) resulted in adiponecrosis within the
      constructs. In contrast, implants with an immature phenotype at the time point of
      implantation (2 and 9 days) gave rise to vascularized, mature adipose tissue in
      vivo. Further, these engineered adipose tissues showed long-term survival in vivo
      over the whole investigation period of 24 weeks. The results of this study can
      contribute to the development of future clinical approaches as they give clear
      evidence which precultivation strategy promotes successful development and long
      term survival of engineered adipose tissue.

PMID- 18333781
TI  - Hard tissue formation in a porous HA/TCP ceramic scaffold loaded with stromal
      cells derived from dental pulp and bone marrow.
AB  - The aim of this study was to compare the ability of hard tissue regeneration of
      four types of stem cells or precursors under both in vitro and in vivo
      situations. Primary cultures of rat bone marrow, rat dental pulp, human bone
      marrow, and human dental pulp cells were seeded onto a porous ceramic scaffold
      material, and then either cultured in an osteogenic medium or subcutaneously
      implanted into nude mice. For cell culture, samples were collected at weeks 0, 1,
      3, and 5. Results were analyzed by measuring cell proliferation rate and alkaline
      phosphatase activity, scanning electron microscopy, and real-time PCR. Samples
      from the implantation study were retrieved after 5 and 10 weeks and evaluated by
      histology and real-time PCR. The results indicated that in vitro abundant cell
      growth and mineralization of extracellular matrix was observed for all types of
      cells. However, in vivo matured bone formation was found only in the samples
      seeded with rat bone marrow stromal cells. Real-time PCR suggested that the
      expression of Runx2 and the expression osteocalcin were important for the
      differentiation of bone marrow stromal cells, while dentin sialophosphoprotein
      contributed to the odontogenic differentiation. In conclusion, the limited hard
      tissue regeneration ability of dental pulp stromal cells questions their
      practical application for complete tooth regeneration. Repeated cell passaging
      may explain the reduction of the osteogenic ability of both bone- and dentinal
      derived stem cells. Therefore, it is essential to develop new cell culture
      methods to harvest the desired cell numbers while not obliterating the osteogenic
      potential.

PMID- 18333782
TI  - Tissue engineering of corneal stromal layer with dermal fibroblasts: phenotypic
      and functional switch of differentiated cells in cornea.
AB  - Previously, we successfully engineered a corneal stromal layer using corneal
      stromal cells. However, the limited source and proliferation potential of corneal
      stromal cells has driven us to search for alternative cell sources for corneal
      stroma engineering. Based on the idea that the tissue-specific environment may
      alter cell fate, we proposed that dermal fibroblasts could switch their phenotype
      to that of corneal stromal cells in the corneal environment. Thus, dermal
      fibroblasts were harvested from newborn rabbits, seeded on biodegradable
      polyglycolic acid (PGA) scaffolds, cultured in vitro for 1 week, and then
      implanted into adult rabbit corneas. After 8 weeks of implantation, nearly
      transparent corneal stroma was formed, with a histological structure similar to
      that of its native counterpart. The existence of cells that had been retrovirally
      labeled with green fluorescence protein (GFP) demonstrated the survival of
      implanted cells. In addition, all GFP-positive cells that survived expressed
      keratocan, a specific marker for corneal stromal cells, and formed fine collagen
      fibrils with a highly organized pattern similar to that of native stroma.
      However, neither dermal fibroblast-PGA construct pre-incubated in vitro for 3
      weeks nor chondrocyte-PGA construct could form transparent stroma. The results
      demonstrated that neonatal dermal fibroblasts could switch their phenotype in the
      new tissue environment under restricted conditions. The functional restoration of
      corneal transparency using dermal fibroblasts suggests that they could be an
      alternative cell source for corneal stroma engineering.

PMID- 18333783
TI  - Great expectations: private sector activity in tissue engineering, regenerative
      medicine, and stem cell therapeutics.
AB  - This report draws upon data from a variety of sources to provide a detailed
      estimate of the current scope of private sector development and commercial
      activity in the aggregate field comprising tissue engineering, regenerative
      medicine, and stem cell therapeutics. Economic activity has grown a remarkable
      fivefold in the past 5 years. As of mid-2007 approximately 50 firms or business
      units with over 3000 employees offered commercial tissue-regenerative products or
      services with generally profitable annual sales in excess of $1.3 billion. Well
      over a million patients have been treated with these products. In addition, 110
      development-stage companies with over 55 products in FDA-level clinical trials
      and other preclinical stages employed approximately 2500 scientists or support
      personnel and spent 850 million development dollars in 2007. These totals
      represent a remarkable recovery from the downturn of 2000-2002, at which time
      tissue engineering was in shambles because of disappointing product launches,
      failed regulatory trials, and the general investment pullback following the dot
      com crash. Commercial success has resulted in large measure from identification
      of products that are achievable with available technology and under existing
      regulatory guidelines. Development-stage firms have become much more adept at
      risk management. The resilience of the field, as well as its current breadth and
      diversity, augurs well for the future of regenerative medicine.

PMID- 18333784
TI  - Defining properties of neural crest-derived progenitor cells from the apex of
      human developing tooth.
AB  - The connective tissue of the human tooth arises from cells that are derived from
      the cranial neural crest and, thus, are termed as "ectomesenchymal cells." Here,
      cells being located in a pad-like tissue adjacent to the apex of the developing
      tooth, which we designated the third molar pad, were separated by the
      microexplant technique. When outgrowing from the explant, dental neural crest
      derived progenitor cells (dNC-PCs) adhered to plastic, proliferated steadily, and
      displayed a fibroblast-like morphology. At the mRNA level, dNC-PCs expressed
      neural crest marker genes like Sox9, Snail1, Snail2, Twist1, Msx2, and Dlx6.
      Cytofluorometric analysis indicated that cells were positive for CD49d (alpha4
      integrin), CD56 (NCAM), and PDGFRalpha, while negative for CD31, CD34, CD45, and
      STRO-1. dNC-PCs could be differentiated into neurogenic, chondrogenic, and
      osteogenic lineages and were shown to produce bone matrix in athymic mice. These
      results demonstrate that human third molar pad possesses neural crest-derived
      cells that represent multipotent stem/progenitor cells. As a rather large amount
      of dNC-PCs could be obtained from each single third molar, cells may be used to
      regenerate a wide range of tissues within the craniofacial region of humans.

PMID- 18333785
TI  - Isolation and cultivation of integrin alpha(6)beta(1)-expressing salivary gland
      graft cells: a model for use with an artificial salivary gland.
AB  - Regeneration of the salivary glands' (SGs) normal function for patients with
      cancer of the head and neck treated with irradiation would be a major
      contribution to their quality of life. This could be accomplished by re
      implantation of autologous SG cells into the residual irradiated tissue or by
      implantation of tissue-engineered artificial SGs. Both methods depend on the
      isolation of cells able to propagate and differentiate into SG epithelial cells.
      Recently, it has been shown that SG integrin alpha(6)beta(1)-expressing (SGIE)
      cells have stem cell capabilities, but these cells could be isolated only after
      duct ligation insult requiring surgical intervention. Because such an invasive
      procedure is not clinically acceptable for these patients, our aim in the present
      study was to explore the use of immuno-magnetic separation of untreated and short
      heat stress-conditioned rats as a less-insulting methodology for enhancement of
      these cells. Our results show that submandibular SGIE cells could be isolated and
      cultivated from untreated animals. However, short heat stress (HS) increased the
      number of isolated SGIE cells 4.7-fold and their proliferation and clonal
      capability 4.6-fold and 3 fold, respectively. We believe that SGIE graft cells
      may be suitable candidates for future tissue-engineered SGs that have been
      damaged by irradiation in patients with head and neck cancer.

PMID- 18333786
TI  - Feasibility study of a novel urinary bladder bioreactor.
AB  - We have devised a bioreactor to simulate normal urinary bladder dynamics. The
      design permits a cell-seeded scaffold made from a modified porcine acellular
      matrix to be placed between 2 closed chambers filled with culture medium and be
      mechanically stimulated in a physiologically relevant manner. Specifically
      designed software increased hydrostatic pressure from 0 to 10 cm of water in a
      linear fashion in 1 chamber, resulting in mechanical stretch and strain on the
      scaffold. Pressure was increased over 55 min (filling) and then decreased to 0
      over 10 s (voiding). Commercially available small intestinal submucosa scaffolds
      were used to test the mechanical capabilities of the bioreactor, and pressure
      waveforms were generated for up to 18 h. Scaffolds were seeded with bladder
      smooth muscle or urothelial cells and incubated in the bioreactor, which
      generated pressure waveforms for 6 h. Scaffold integrity was preserved as seen
      through Masson's trichrome staining. No obvious contamination of the system was
      noted. Hematoxylin and eosin staining showed presence of cells after incubation
      in the bioreactor, and immunohistochemistry and real-time reverse transcriptase
      polymerase chain reaction suggested continued cellular activity. Cellular
      orientation tended to be perpendicular to the applied pressure. Preliminary
      results suggest that our bioreactor is a suitable model for simulating normal
      physiological conditions of bladder cycling in an ex vivo system.

PMID- 18333787
TI  - A biomaterial composed of collagen and solubilized elastin enhances angiogenesis
      and elastic fiber formation without calcification.
AB  - Elastin is the prime protein in elastic tissues that contributes to elasticity
      of, for example, lung, aorta, and skin. Upon injury, elastic fibers are not
      readily replaced, which hampers tissue regeneration. Incorporation of solubilized
      elastin (hydrolyzed insoluble elastin fibers or elastin peptides) in biomaterials
      may improve regeneration, because solubilized elastin is able to promote
      proliferation as well as elastin synthesis. Porous biomaterials composed of
      highly purified collagen without and without elastin fibers or solubilized
      elastin were prepared by freezing and lyophilization. Solubilized elastin formed
      spherical structures that were incorporated in the collagenous part of the
      scaffolds and that persisted after chemical crosslinking of the scaffolds.
      Crosslinked scaffolds were subcutaneously implanted in young Sprague Dawley rats.
      Collagen-solubilized elastin and collagen scaffolds showed no calcification in
      this sensitive calcification model, in contrast to scaffolds containing elastin
      fibers. Collagen-solubilized elastin scaffolds also induced angiogenesis, as
      revealed by type IV collagen staining, and promoted elastic fiber synthesis, as
      shown with antibodies against rat elastin and fibrillin-1. It is concluded that
      scaffolds produced from collagen and solubilized elastin present a non-calcifying
      biomaterial with a capacity for soft-tissue regeneration, especially in relation
      to elastic fiber synthesis.

PMID- 18333788
TI  - In vivo pulmonary tissue engineering: contribution of donor-derived endothelial
      cells to construct vascularization.
AB  - Intrapulmonary engraftment of engineered lung tissues could provide a potential
      therapeutic approach for the treatment of pediatric and adult pulmonary diseases.
      In working toward this goal, we report here on in vivo generation of vascularized
      pulmonary tissue constructs utilizing the subcutaneous Matrigel plug model. Mixed
      populations of murine fetal pulmonary cells (FPCs) containing epithelial,
      mesenchymal, and endothelial cells (ECs) were isolated from the lungs of
      embryonic day 17.5 fetuses. FPCs were admixed to Matrigel and injected
      subcutaneously into the anterior abdominal wall of adult C57/BL6 mice to
      facilitate in vivo pulmonary tissue construct formation. Vascularization was
      enhanced by placing fibroblast growth factor 2 (FGF2)-loaded polyvinyl sponges
      into the hydrogel. After 1 week, routine histology and immunohistochemical
      staining for donor-derived epithelial cells and ECs as well as analysis of patent
      vasculature in the constructs following tail vein injection of fluorescein
      isothiocyanate-conjugated dextran were performed. In the Matrigel-only controls,
      some level of host infiltrate, but no measurable vascularization, was detected.
      In the presence of FPCs, the constructs contained ductal epithelial structures
      and patent vasculature. In the absence of FPCs, exogenous FGF2 induced the
      formation of numerous patent blood vessels throughout the entire constructs; in
      combination with FPCs, it resulted in enhanced capillary density and abundant
      interfacing between developing epithelial and vascular structures. The
      significant findings of this study are that distal pulmonary epithelial
      differentiation (as assessed by the expression of prosurfactant protein C) can be
      maintained in vivo and that donor-derived ECs contribute to the formation of
      patent vessels that interface tightly with ductal epithelial structures.

PMID- 18333789
TI  - Seeding bioreactor-produced embryonic stem cell-derived cardiomyocytes on
      different porous, degradable, polyurethane scaffolds reveals the effect of
      scaffold architecture on cell morphology.
AB  - A successful regenerative therapy to treat damage incurred after an ischemic
      event in the heart will require an integrated approach including methods for
      appropriate revascularization of the infarct site, mechanical recovery of damaged
      tissue, and electrophysiological coupling with native cells. Cardiomyocytes are
      the ideal cell type for heart regeneration because of their inherent electrical
      and physiological properties, and cardiomyocytes derived from embryonic stem
      cells (ESCs) represent an attractive option for tissue-engineering therapies. An
      important step in developing tissue engineering-based approaches to cardiac cell
      therapy is understanding how scaffold architecture affects cell behavior. In this
      work, we generated large numbers of ESC-derived cardiomyocytes in bioreactors and
      seeded them on porous, 3-dimensional scaffolds prepared using 2 different
      techniques: electrospinning and thermally induced phase separation (TIPS). The
      effect of material macro-architecture on the adhesion, viability, and morphology
      of the seeded cells was determined. On the electrospun scaffolds, cells were
      elongated in shape, a morphology typical of cultured ESC-derived cardiomyocytes,
      whereas on scaffolds fabricated using TIPS, the cells retained a rounded
      morphology. Despite these gross phenotypic and physiological differences,
      sarcomeric myosin and connexin 43 expression was evident, and contracting cells
      were observed on both scaffold types, suggesting that morphological changes
      induced by material macrostructure do not directly correlate to functional
      differences.

PMID- 18333790
TI  - Microstructures in 3D biological gels affect cell proliferation.
AB  - Controlling the microscale environment in three-dimensional (3D) matrices for
      tissue engineering applications is a challenging but necessary goal. In this
      work, the effect of discrete microscale structures (microrods) on cell
      proliferation was assessed in 3D gels. Microrods were fabricated out of SU-8 with
      dimensions of 100 x 15 x 15 microm (L x H x W) and incorporated into Matrigel
      seeded with fibroblasts. The 3D microrod-Matrigel composite system inhibited
      proliferation of both primary and cell-line fibroblasts compared to cells seeded
      in Matrigel alone. To rule out bulk mechanical effects, the bulk shear modulus
      (G') and loss modulus (G") were assessed between 0.1 and 5 Hz for both Matrigel
      and microrod-Matrigel composites. The incorporation of microrods did not change
      the bulk stiffness of the gel. Moreover, it was determined that the chemistry of
      the microrod material itself did not inhibit cell proliferation. Therefore,
      results indicate that the presence of suspended microscale structures in three
      dimensions can regulate cell proliferation in a dose-dependent manner. This
      system provides a biocompatible, long-term way to modulate cell growth in 3D
      cultures and is amenable to in vivo applications.

PMID- 18333791
TI  - In vitro proliferation and differentiation of human mesenchymal stem cells
      cultured in autologous plasma derived from bone marrow.
AB  - Expansion of human mesenchymal stem cells (hMSCs) in medium supplemented with
      fetal bovine serum (FBS) has a potential risk of transmitting viral and prion
      diseases and causing immunological rejection. The aim of our present study was to
      find a substitute for the traditional FBS in culture of hMSCs to facilitate the
      clinical application of hMSCs. We used autologous plasma derived from bone marrow
      (APM) as a substitute for FBS and found that, when cultured with APM, the cell
      surface markers and the proportion of hMSCs in the G(0)/G(1) phase and the
      S+G(2)/M phase resembled those cultured with FBS. However, there were fewer early
      apoptotic cells in APM-supplemented medium than in FBS (p < 0.01). APM resulted
      in much greater thymidine incorporation than FBS (p < 0.001). There were
      significantly more alkaline phosphatase (ALP)-positive fibroblast colony-forming
      units (CFU-Fs) covering larger areas in APM than in FBS (p < 0.01). Also, APM
      induced greater ALP activity, more mineralized nodules, and greater expression of
      osteogenic genes than did FBS. In addition, when cultured in adipogenic medium,
      there were fewer oil-red O-positive cells and lower expression of adipogenic gene
      with APM than with FBS. In conclusion, expansion of hMSCs in APM-supplemented
      medium instead of traditional FBS is more advantageous. It could promote cell
      proliferation, enhance osteogenic differentiation, and suppress adipogenic
      differentiation of hMSCs and is therefore a safer and more effective substitute
      for FBS in clinical cytotherapy processes.

PMID- 18333792
TI  - Compositional alterations of fibrin-based materials for regulating in vitro
      neural outgrowth.
AB  - The purpose of this investigation was to evaluate dorsal root ganglion (DRG) cell
      outgrowth in a biosynthetic material made from PEGylated fibrinogen and in
      thrombin-polymerized fibrin hydrogels. The hypothesis stipulated that changing
      the composition of the biosynthetic constituents of the hydrogel can be used to
      better regulate the rate of DRG cell invasion when compared to reconstituted
      fibrin hydrogels. The composition of the biosynthetic hydrogel was controlled by
      the relative amount of poly(ethylene glycol) (PEG) to fibrinogen or by the
      fibrinogen concentration in the material. Other PEGylated protein hydrogels
      including PEGylated collagen and PEGylated albumin were used as positive and
      negative controls, respectively, for DRG cell outgrowth studies. The PEGylated
      fibrinogen hydrogels readily supported extensive outgrowth of sprouting neurites
      and invading glial cells from encapsulated DRGs in the presence of nerve growth
      factor. The PEGylated fibrinogen hydrogels exhibited preferential neurite
      invasion whereby the nonneuronal cells were observed lagging behind the invading
      neurites. Hydrogels containing more PEG or fibrinogen reduced the lag between the
      cell types and also the overall rate of the cellular invasion. Time-lapse video
      microscopy and quantitative cellular invasion data were used to illustrate the
      effectiveness of controlling DRG cell outgrowth characteristics in PEGylated
      fibrinogen hydrogels when compared to their respective reconstituted protein
      hydrogel counterparts.

PMID- 18333793
TI  - Tissue engineering by self-assembly of cells printed into topologically defined
      structures.
AB  - Understanding the principles of biological self-assembly is indispensable for
      developing efficient strategies to build living tissues and organs. We exploit
      the self-organizing capacity of cells and tissues to construct functional living
      structures of prescribed shape. In our technology, multicellular spheroids (bio
      ink particles) are placed into biocompatible environment (bio-paper) by the use
      of a three-dimensional delivery device (bio-printer). Our approach mimics early
      morphogenesis and is based on the realization that the genetic control of
      developmental patterning through self-assembly involves physical mechanisms.
      Three-dimensional tissue structures are formed through the postprinting fusion of
      the bio-ink particles, in analogy with early structure-forming processes in the
      embryo that utilize the apparent liquid-like behavior of tissues composed of
      motile and adhesive cells. We modeled the process of self-assembly by fusion of
      bio-ink particles, and employed this novel technology to print extended cellular
      structures of various shapes. Functionality was tested on cardiac constructs
      built from embryonic cardiac and endothelial cells. The postprinting self
      assembly of bio-ink particles resulted in synchronously beating solid tissue
      blocks, showing signs of early vascularization, with the endothelial cells
      organized into vessel-like conduits.

PMID- 18333794
TI  - In situ polymerization of a conductive polymer in acellular muscle tissue
      constructs.
AB  - We present a method to chemically deposit a conductive polymer, poly(3,4
      ethylenedioxythiophene) (PEDOT), on acellularized muscle tissue constructs.
      Morphology and structure of the deposition was characterized using optical and
      scanning electron microscopies (SEM). The micrographs showed elongated, smooth,
      tubular PEDOT structures completely penetrating and surrounding the tissue
      fibers. The chemical polymerization was performed using iron chloride, a mild
      oxidizer. Remaining iron and chlorine in the tissue constructs were reduced to
      acceptable metabolic levels, while preserving the structural integrity of the
      tissue. We expect that these acellular, polymerized tissue implants will remain
      essentially unmodified in cellular environments in vitro and in vivo because of
      the chemical and thermal stability of the PEDOT polymer depositions. Our results
      indicate that in situ polymerization occurs throughout the tissue, converting it
      into an extensive acellular, non-antigenic substrate of interest for in vivo
      experiments related to nerve repair and bioartificial prosthesis. We expect these
      conducting polymer scaffolds to be useful for direct integration with
      electronically and ionically active tissues.

PMID- 18333795
TI  - An islet-stabilizing implant constructed using a preformed vasculature.
AB  - Islet transplantation for the purpose of treating insulin-sensitive diabetes is
      currently limited by several factors, including islet survival
      posttransplantation. In the current study, a tissue-engineered prevascularized
      pancreatic encapsulating device (PPED) was developed. Isolated islets were placed
      in collagen gels, and they exhibited fourfold more insulin release than islets
      not in collagen. The insulin released by beta-cells in islets encapsulated in
      collagen exhibited unobstructed diffusion within the collagen gels. Subsequent
      studies evaluated the ability to create a sandwich comprised of two layers of
      prevascularized collagen gels around a central collagen gel containing islets. In
      vitro characterization of the islets showed that islets are functional and
      responded to glucose stimulation. The PPEDs were implanted subcutaneously into
      severe combined immunodeficient mice. Islet survival was assessed after 7, 14,
      and 28 days. Immunohistochemical analysis was performed on the implants to detect
      insulin and the presence of intraislet endothelial cells. At all time points,
      insulin was localized in association with intact and partially dissociated
      islets. Moreover, cells that exhibited insulin staining were colocalized with
      intraislet endothelial cells. These data indicate that the PPED enhances islet
      survival by supporting islet viability and maintaining intraislet endothelial
      cell structures.

PMID- 18333796
TI  - Differential effects of natriuretic peptide stimulation on tissue-engineered
      cartilage.
AB  - Tissue engineering is a promising approach for articular cartilage repair;
      however, it still has proven a challenge to produce substantial quantities of
      tissue from the limited number of cells that can be extracted from a single
      individual. Although several approaches have been investigated to enhance the
      production of cartilaginous tissue in vitro, relatively few techniques exist to
      reliably increase the population of cells needed for this approach.
      Alternatively, a single modulator of chondrocyte function, such as the C-type
      natriuretic peptide (CNP), may serve to address both of these issues. CNP is
      expressed in the growth plate and regulates cartilage growth through chondrocyte
      proliferation and differentiation. Thus, the purpose of this study was to
      determine the effects of CNP stimulation on tissue-engineered cartilage. Isolated
      bovine articular chondrocytes were seeded on Millicell filters and cultured in
      the presence of CNP (10 pM to 10 nM) for 4 weeks. Stimulation with CNP resulted
      in differential effects depending on the dose of the peptide. Low doses of CNP
      (10 to 100 pM) elicited chondrocyte proliferation with a maximal response
      observed at 100 pM (43% increase in cellularity). However, high doses of CNP (10
      nM) stimulated matrix deposition (36% and 137% increase in proteoglycans and
      collagen) without an associated change in tissue cellularity. CNP stimulation
      also downregulated the expression of type X collagen, an early hypertrophic
      marker associated with endochondral ossification. Thus, by regulating the dose of
      CNP, it may be possible to produce engineered tissue from the limited number of
      cells that can be reasonably extracted from a single individual for therapeutic
      purposes.

PMID- 18333797
TI  - Heparanase enhances early hepatocyte inclusion in the recipient liver after
      transplantation in partially hepatectomized rats.
AB  - Hepatocyte transplantation is an emerging approach for the treatment of liver
      diseases. However, broad clinical application of this method has been limited by
      restricted source of cells and low efficiency of cell integration within the
      recipient liver. Heparanase cleaves heparan sulfate proteoglycans in the
      extracellular matrix and basement membrane, activity that affects cellular
      invasion associated with cancer metastasis and inflammation. This activity has a
      multifunctional effect on cell-cell interaction, cell adhesion, and angiogenesis.
      All these factors are important for successful integration of transplanted
      hepatocytes. Male donor hepatocytes pretreated with heparanase or untreated were
      transplanted into recipient female rat spleen following partial hepatectomy.
      Engraftment efficacy was evaluated by PCR for Y chromosome, histology and PCNA,
      and heparanase immunohistochemistry. In addition, proliferative activity of
      hepatocytes in vitro was determined by bromodeoxyuridine immunostaining. The
      number of heparanase-treated cells detected in the recipient liver was
      significantly increased three- to fivefold within 24-48 h posttransplantation and
      twofold at 14 days compared with untreated cells. The transplanted hepatocytes
      treated with heparanase were clearly seen inside portal vein radicles as cell
      aggregates up to 72 h posttransplantation. The number of portal radicles filled
      with heparanase-treated hepatocytes was increased compared to control early after
      transplantation. Heparanase treatment enhanced hepatocyte and sinusoidal
      endothelial cell proliferation in the liver, and hepatocyte proliferation within
      the spleen tissue. Preliminary in vitro studies with isolated hepatocytes treated
      with heparanase showed increased proliferative activity within 24-48 h of cell
      culture. These results suggest that preincubation of hepatocytes with heparanase
      increases the presence of hepatocytes within the recipient liver early following
      cell transplantation and stimulates both hepatocyte and sinusoidal endothelial
      cell proliferation.

PMID- 18333798
TI  - Accessing the tissue engineering literature: a new paradigm.

PMID- 18333800
TI  - Mature human hepatocytes from ex vivo differentiation of alginate-encapsulated
      hepatoblasts.
AB  - Alginate gel was used to provide encapsulation to support the growth and
      eventually the differentiation of hepatic progenitors cells derived from human
      fetal livers. The encapsulated cells aggregated into spheroids within a few days
      in culture and continued to grow for at least 4 weeks in a serum-free medium. The
      hepatic progenitor cells in the spheroids undergo differentiation, as indicated
      by the appearance of functions of mature hepatocytes such as the detoxification
      of ammonia, albumin secretion, expression of the adult cytochrome P450 isozyme
      CYP3A4 and enzymatic activity typical of CYP2C9. Along with the expression of
      mature hepatic markers, these progenitor cells lost features typical of immature
      liver cells such as epithelial cell adhesion molecule. In addition to the
      acquisition of mature biochemical functions, the spheroids also developed a bile
      ducts, suggesting that they had differentiated into tissues resembling those in
      an intact liver.

PMID- 18333801
TI  - Regulable vascular endothelial growth factor165 overexpression by ex vivo
      expanded keratinocyte cultures promotes matrix formation, angiogenesis, and
      healing in porcine full-thickness wounds.
AB  - The intricate wound repair process involves the interplay of numerous cells and
      proteins. Using a porcine full-thickness wound (FTW) healing model, we
      hypothesized that the ex vivo gene transfer of vascular endothelial growth factor
      (VEGF)-transfected basal keratinocyte (KC) cell suspensions may generate cross
      talk and induce matrix formation, angiogenesis, and accelerated healing.
      Moreover, to regulate overexpression of isoform 165 of VEGF and its effect on
      healing, we introduced a tetracycline (TC)-inducible gene switch in the
      expression plasmid. Autologous basal KCs were cultivated from the porcine donor
      and transfected using cationic liposomes. A dose-response curve was established
      to determine optimal activation of the gene switch by TC. In vivo, FTWs were
      treated with VEGF-transfected KCs and controls. Wound fluids were collected daily
      and examined using enzyme-linked immunosorbent assay. Biopsies were evaluated
      using hematoxylin and eosin and immunostaining for fibronectin, CD144, and lectin
      BS-1. In vitro, highest regulable VEGF165-expression was obtained with 1
      microg/mL of TCs. In vivo, after induction of the gene switch by adding 1
      microg/mL of TCs to the FTW, we obtained upregulated VEGF165 levels and enhanced
      fibronectin deposition and found more endothelial cell tubular formations and
      higher rates of reepithelialization than in controls. This ex vivo gene transfer
      model may serve as a platform for vascular induction in full-thickness tissue
      repair.

PMID- 18333802
TI  - No increased bone formation around alendronate or omeprazole loaded bioactive
      bone cements in a femoral defect.
AB  - Alendronate and omeprazole have been found to influence bone healing by
      interfering with osteoclastic activity, resulting in increased bone formation.
      The biological effect of these conventional drugs, incorporated into bioactive
      bone cement (G2B1), was investigated in a rabbit model. The 2 materials and a
      control were inserted in defects created in the femoral condyle of rabbits.
      Implantation time was 6 and 12 weeks. After retrieval, micro-computed tomography
      and histomorphometry were performed to quantify bone mineral density (BMD) and
      bone volume (BV) of the implant-surrounding bone mass and the percentage of bone
      to-implant contact. BMD and BV were similar in all groups. The percentage of bone
      to-implant contact was significantly lower in the alendronate and omeprazole
      groups than in controls after 6 weeks of implantation. After 12 weeks, this
      difference in bone contact disappeared for the omeprazole but not for the
      alendronate implants, which were almost completely surrounded by a fibrous
      capsule, associated with a limited inflammatory response. In conclusion, in the
      current study, alendronate and omeprazole did not result in better bone healing
      when incorporated into bioactive bone cement than did plain control implants.
      Moreover, an additional cytotoxicity assay revealed that alendronate evoked a
      toxic response.

PMID- 18333803
TI  - Effects of dispensing pressure and nozzle diameter on cell survival from solid
      freeform fabrication-based direct cell writing.
AB  - Novel technologies are emerging that incorporate cells as part of the building
      blocks for various biomanufacturing processes, such as solid freeform fabricated
      tissue constructs for tissue regeneration, three-dimensional pharmacokinetic
      models, cell-based microelectromechanical systems, sensors, and microfluidic
      devices. However, the effects of these biomanufacturing processes on cells have
      not been fully studied. This paper examines the effect of solid freeform
      fabrication-based direct cell writing process, focusing on dispensing pressure
      and nozzle size, on the viability and functional behavior of HepG2 cells
      encapsulated within alginate. Our experimental results revealed a process-induced
      mechanical damage to cell membrane integrity, causing a quantifiable loss in cell
      viability due to incremental increases and decreases in the studied process
      parameters of dispensing pressure and nozzle size, respectively. The experimental
      results also suggested that cells may require a recovery period following direct
      cell writing biofabrication. The general finding of this study may be applicable
      to freeform fabrication of cell-based tissue constructs and three-dimensional
      biological models.

PMID- 18333804
TI  - Effect of mechanical loading on three-dimensional cultures of embryonic stem cell
      derived cardiomyocytes.
AB  - Cardiomyocytes selected from murine embryonic stem cells (ESCs) using the cardiac
      specific promoter alpha-myosin heavy chain were embedded into collagen and
      fibronectin scaffolds. A custom-built device was used to expose these constructs
      to mechanical loading (10% stretch at 1, 2, or 3 Hz) or no loading. Constructs
      were evaluated using reverse transcriptase polymerase chain reaction, histology,
      and immunohistochemistry. Mechanical loading significantly affected gene
      expression, and these changes were dependent on the frequency of stretch. A 1 Hz
      cyclical stretch resulted in significantly lower gene expression, whereas a 3 Hz
      cyclical stretch resulted in significantly greater gene expression than in
      unstretched controls. These constructs also developed cardiac-specific cell
      structures similar to those found in vivo. This study describes a 3-dimensional
      model to examine the direct effect of mechanical loading on the differentiation
      of ESC-derived cardiomyocytes embedded in a defined extracellular matrix
      scaffold. A technique was also developed to isolate the areas within the
      constructs undergoing the most homogeneous strain so that the effect of
      mechanical loading on gene expression could be directly evaluated. These
      experiments emphasize that ESC-derived cardiomyocytes are actively responding to
      cues from their environment and that those cues can drive phenotypic control and
      cardiomyocyte differentiation.

PMID- 18333805
TI  - Gradients in the liver's extracellular matrix chemistry from periportal to
      pericentral zones: influence on human hepatic progenitors.
AB  - Embryonic mesenchymal feeders produce paracrine signals requisite for ex vivo
      survival and expansion of hepatic progenitors. The signals consist of a subset of
      soluble factors found in conditioned medium, and a subset of insoluble factors
      found in extracellular matrix that include collagens and basal adhesion
      molecules. We have identified key matrix components required for ex vivo
      maintenance of human hepatic progenitors produced by biologically active feeders.
      These components are similar to those found in zone 1 of the liver acinus (e.g.,
      space of Disse) between layers of parenchyma and endothelia. Within these layers
      are transition chemistry matrix gradients, from zone 1 to zone 3. Use of purified
      zone 1 matrix components enables attachment and expansion of human hepatic
      progenitors independent of feeders. Cells aggregated into spheroid-like
      structures on laminin or spread into monolayers on type III or IV collagens.
      Contrastingly, a zone 3 matrix component, type I collagen, elicited growth arrest
      and differentiation. Another zone 3 matrix component, fibronectin, inhibited
      attachment. Use of specific matrix components, along with soluble paracrine
      signals from feeders, should enable one to maintain hepatic progenitors ex vivo
      without feeders and under wholly defined conditions.

PMID- 18333806
TI  - Non-viral bone morphogenetic protein 2 transfection of rat dental pulp stem cells
      using calcium phosphate nanoparticles as carriers.
AB  - Calcium phosphate nanoparticles have shown potential as non-viral vectors for
      gene delivery. The aim of this study was to induce bone morphogenetic protein
      (Bmp)2 transfection in rat dental pulp stem cells using calcium phosphate
      nanoparticles as a gene vector and then to evaluate the efficiency and
      bioactivity of the transfection. We also intended to investigate the behavior of
      transfected cells when seeded on 3-dimensional titanium fiber mesh scaffolds.
      Nanoparticles of calcium phosphate encapsulating plasmid deoxyribonucleic acid
      (DNA) (plasmid enhanced green fluorescent protein-BMP2) were prepared. Then, STRO
      1-selected rat dental pulp stem cells were transfected using these nanoparticles.
      Transfection and bioactivity of the secreted BMP2 were examined. Thereafter, the
      transfected cells were cultured on a fibrous titanium mesh. The cultures were
      investigated using scanning electron microscipy and evaluated for cell
      proliferation, alkaline phosphatase activity and calcium content. Finally, real
      time polymerase chain reaction was performed for odontogenesis-related gene
      expression. The results showed that the size of the DNA-loaded particles was
      approximately 100 nm in diameter. Nanoparticles could protect the DNA
      encapsulated inside from external DNase and release the loaded DNA in a low-acid
      environment (pH 3.0). In vitro, nanoparticle transfection was shown to be
      effective and to accelerate or promote the odontogenic differentiation of rat
      dental pulp stem cells when cultured in the 3-dimensional scaffolds. Based on our
      results, plasmid DNA-loaded calcium phosphate nanoparticles appear to be an
      effective non-viral vector for gene delivery and functioned well for odontogenic
      differentiation through Bmp2 transfection.

PMID- 18333807
TI  - Functional tissue-engineered valves from cell-remodeled fibrin with commissural
      alignment of cell-produced collagen.
AB  - Heart valve replacements composed of living tissue that can adapt, repair, and
      grow with a patient would provide a more clinically beneficial option than
      current inert replacements. Bioartificial valves were produced by entrapping
      human dermal fibroblasts within a fibrin gel. Using a mold design that presents
      appropriate mechanical constraints to the cell-induced fibrin gel compaction,
      gross fiber alignment (commissure-to-commissure alignment in the leaflets and
      circumferential alignment in the root) and the basic geometry of a native aortic
      valve were obtained. After static incubation on the mold in complete medium
      supplemented with transforming growth factor beta 1, insulin, and ascorbate,
      collagen fibers produced by the entrapped cells were found to coalign with the
      fibrin based on histological analyses. The resultant tensile mechanical
      properties were anisotropic. Ultimate tensile strength and tensile modulus of the
      leaflets in the commissural direction were 0.53 and 2.34 MPa, respectively. The
      constructs were capable of withstanding backpressure commensurate with porcine
      aortic valves in regurgitation tests (330 mmHg) and opened and closed under
      physiological pressure swings of 10 and 20 mmHg, respectively. These data support
      proof of principle of using cell-remodeled fibrin gel to produce tissue
      engineered valve replacements.

PMID- 18333808
TI  - Expression of CXC chemokines and their receptors is modulated during chondrogenic
      differentiation of human mesenchymal stem cells grown in three-dimensional
      scaffold: evidence in native cartilage.
AB  - Chemokines contribute to the maintenance of cartilage homeostasis. To evaluate
      the role of CXC chemokines CXCL8 (interleukin-8), CXCL10 (interferon-gamma
      inducible protein-10), CXCL12 (stroma-derived factor-1) and CXCL13 (B-cell
      attracting chemokine-1) and their receptors, respectively CXCR1-2, CXCR3, CXCR4,
      and CXCR5, during chondrogenic differentiation of human mesenchymal stromal cells
      (h-MSCs), we used a well-defined in vitro model. Chondrogenic differentiation was
      analyzed on h-MSCs grown on hyaluronic acid-based biomaterial in the presence or
      absence of transforming growth factor-beta, and the expression and modulation of
      CXC chemokines and receptors were evaluated at different time points. Real-time
      polymerase chain reaction was performed to analyze their expression at the
      messenger ribonucleic acid (mRNA) level, and immunohistochemistry and enzyme
      linked immunosorbent assay were used to evaluate their expression at the protein
      level. Human articular cartilage biopsies were used to evaluate chemokine and
      receptor expression in normal tissue. We found no expression of CXCR1, CXCR2,
      CXCR3, or CXCL10 at the mRNA level. CXCL8 mRNA was down-modulated, whereas at the
      protein level, we found greater release of this chemokine. CXCR4 and its ligand
      CXCL12 were down-modulated during chondrogenesis. By contrast, CXCR5 was up
      regulated, whereas its ligand CXCL13 was lower. These data were also confirmed on
      human articular cartilage. These findings show that, during in vitro h-MSC
      chondrogenic differentiation, chemokine and receptor expression was specifically
      induced or repressed. This was in line with what the authors also found in normal
      articular cartilage, suggesting a role in differentiation and maturation of a
      cartilage-like structure in vitro and consequently the regulation of cartilage
      homeostasis.

PMID- 18333809
TI  - Proliferation, osteogenic differentiation, and distribution of rat bone marrow
      stromal cells in nonwoven fabrics by different culture methods.
AB  - The proliferation, osteogenic differentiation, and distribution patterns of
      stromal cells from rat bone marrow were investigated in a three-dimensional
      nonwoven fabric of polyethylene terephthalate fiber by the static, agitated, and
      stirred culture methods; stirring speeds were 10, 50, and 100 rpm in the stirred
      culture method. The culture method affected the time profile of proliferation and
      osteogenic differentiation of cells or their distribution in the fabric. The
      extent of cell proliferation and osteogenic differentiation became higher in
      order of the stirred at 100 rpm = the stirred at 50 rpm > the stirred at 10 rpm >
      the agitated > the static methods. In addition, the cells were more uniformly
      proliferated in the fabric by the stirred culture method with time than they were
      proliferated in the fabric by other methods. The alkaline phosphatase (ALP)
      activity and calcium content were higher for cells cultured by the stirred
      culture method than those cultured by other methods. The total ALP activity,
      calcium content, and bone mineral density were higher for every stirred method
      than those for other methods. However, the distribution uniformity of cells
      differentiated was low irrespective of the culture method. It is concluded that
      the extent of proliferation and differentiation of cells or their distribution
      uniformity in the nonwoven fabrics was influenced by the culture method.

PMID- 18333810
TI  - Ex Vivo bone formation in bovine trabecular bone cultured in a dynamic 3D
      bioreactor is enhanced by compressive mechanical strain.
AB  - Our aim was to test cell and trabecular responses to mechanical loading in vitro
      in a tissue bone explant culture model. We used a new three-dimensional culture
      model, the ZetOS system, which provides the ability to exert cyclic compression
      on cancellous bone cylinders (bovine sternum) cultured in forced flow
      circumfusion chambers, and allows to assess mechanical parameters of the
      cultivated samples. We evaluated bone cellular parameters through osteocyte
      viability test, gene and protein expression, and histomorphometric bone formation
      rate, in nonloaded versus loaded samples. The microarchitecture of bone cores was
      appraised by in vivo micro-CT imaging. After 3 weeks, the samples receiving daily
      cyclic compression exhibited increased osteoblast differentiation and activity
      associated with thicker, more plate-like-shaped trabeculae and higher Young's
      modulus and ultimate force as compared to unloaded samples. Osteoclast activity
      was not affected by mechanical strain, although it was responsive to drug
      treatments (retinoic acid and bisphosphonate) during the first 2 weeks of
      culture. Thus, in the ZetOS apparatus, we reproduce in vitro the osteogenic
      effects of mechanical strain known in vivo, making this system a unique and an
      essential laboratory aid for ex vivo testing of lamellar bone remodeling.

PMID- 18333811
TI  - Three-dimensional fiber deposition of cell-laden, viable, patterned constructs
      for bone tissue printing.
AB  - Organ or tissue printing, a novel approach in tissue engineering, creates
      layered, cell-laden hydrogel scaffolds with a defined three-dimensional (3D)
      structure and organized cell placement. In applying the concept of tissue
      printing for the development of vascularized bone grafts, the primary focus lies
      on combining endothelial progenitors and bone marrow stromal cells (BMSCs). Here
      we characterize the applicability of 3D fiber deposition with a plotting device,
      Bioplotter, for the fabrication of spatially organized, cell-laden hydrogel
      constructs. The viability of printed BMSCs was studied in time, in several
      hydrogels, and extruded from different needle diameters. Our findings indicate
      that cells survive the extrusion and that their subsequent viability was not
      different from that of unprinted cells. The applied extrusion conditions did not
      affect cell survival, and BMSCs could subsequently differentiate along the
      osteoblast lineage. Furthermore, we were able to combine two distinct cell
      populations within a single scaffold by exchanging the printing syringe during
      deposition, indicating that this 3D fiber deposition system is suited for the
      development of bone grafts containing multiple cell types.

PMID- 18333812
TI  - Critical Steps toward a tissue-engineered cartilage implant using embryonic stem
      cells.
AB  - Embryonic stem (ES) cells are a potential source for cartilage tissue engineering
      because they provide an unlimited supply of cells that can be differentiated into
      chondrocytes. So far, chondrogenic differentiation of both mouse and human ES
      cells has only been demonstrated in two-dimensional cultures, in pellet cultures,
      in a hydrogel, or on thin biomaterials. The next challenge will be to form
      cartilage on a load-bearing, clinically relevant-sized scaffold in vitro and in
      vivo, to regenerate defects in patients suffering from articular cartilage
      disorders. For a successful implant, cells have to be seeded efficiently and
      homogenously throughout the scaffold. Parameters investigated were the scaffold
      architecture, seeding method, and cellular condition. Seeding in a three
      dimensional fiber-deposited (3DF) scaffold was more homogenous than in a
      compression-molded scaffold. The seeding efficiency on bare scaffolds was
      compromised by the absence of serum in the chondrogenic medium, but could be
      improved by combining the cells with a gel and subsequent injection into the 3DF
      scaffolds. However, the viability of the cells was unsatisfactory in the interior
      of the graft. Cell aggregates, the so-called embryoid bodies (EBs), were seeded
      with increased survival rate. Mouse ES cells readily underwent chondrogenic
      differentiation in vitro in pellets, on bare scaffolds, in Matrigel, and in
      agarose, both as single cells and in EBs. The differentiation protocol requires
      further improvement to achieve homogenous differentiation and abolish teratoma
      formation in vivo. We conclude that ES cells can be used as a cell source for
      cartilage tissue engineering, pending further optimization of the strategy.

PMID- 18333813
TI  - Soluble factor-dependent in vitro growth and maturation of rat fetal liver cells
      in a three-dimensional culture system.
AB  - Fetal liver cell fractions are potent sources of cells for future liver tissue
      engineering, by virtue of their high proliferation capacity and their potential
      for hepatic maturation. Recently, some types of hepatic differentiation agents
      have been identified from findings in stem cell biology. We therefore
      investigated the in vitro growth and maturation of rat fetal liver cells isolated
      from 17-day-old pregnant rats in poly-L-lactic acid three-dimensional (3D)
      macroporous scaffolds in the presence of soluble factors, such as a combination
      of hepatocyte growth factor, fibroblast growth factor-1, and fibroblast growth
      factor-4, oncostatin M, and sodium butyrate. Inclusion of all these factors in
      the 3D culture induced higher levels of hepatic functions and well maintained
      these enhanced levels during 2 weeks of culture, whereas in the monolayer
      culture, such functional enhancement was gradually lost after 1 week. The finally
      achieved functions on a per-cell basis in the 3D culture with all of the soluble
      factors were comparable to those of adult hepatocytes. We therefore conclude that
      the 3D culture system shows promise for the in vitro maturation of fetal liver
      cells as a means of preconditioning of the cells for engineered liver tissue
      equivalents in future transplantation studies.

PMID- 18333814
TI  - The influence of serum-free culture conditions on skeletal muscle differentiation
      in a tissue-engineered model.
AB  - The influence of differentiation medium (DM) components on C2C12 murine myoblast
      differentiation has only been studied in monolayer cultures. Serum-free
      formulations have been applied that omit the use of sera with unknown
      composition. The goal of the present study was to compare the influence of serum
      free media on C2C12 differentiation in 3-dimensional tissue-engineered muscle
      constructs. Myoblast proliferation and differentiation in media containing
      Ultroser G (DMU), insulin-like growth factor (IGF)-I (DMI), or both (DMUI) were
      compared with those induced by more-traditional media containing horse serum (HS)
      or horse serum and IGF-I (HSI). Effects of the applied media were assessed from
      gross construct morphology, total protein content, creatine kinase activity, and
      tissue viability. Addition of IGF-I (HSI) to the standard DM (HS) improved
      myoblast differentiation in muscle constructs. Even better results were obtained
      using DMU and DMUI culture conditions. DMI could not induce differentiation or
      maintain cell viability. Serum-free culture medium supplemented with DMU or DMUI
      accelerates and improves myoblast differentiation in engineered muscle tissue
      better than the gold standard HS.

PMID- 18333815
TI  - Influence of matrix processing on the optical and biomechanical properties of a
      corneal stroma equivalent.
AB  - Interest in developing tissue-engineered cornea has increased with the decrease
      in the supply of donor tissue; however, the high strength and transparency of the
      cornea present a challenge. Both the collagen processing and crosslinking methods
      were hypothesized to influence the optical and biomechanical properties of
      collagen matrices, while regular surface topography was hypothesized to align
      stromal fibroblasts. Improved transparency and strength were observed when
      soluble tropocollagen was added to the insoluble collagen and when glucose
      mediated ultraviolet (UV) crosslinking as opposed to dehydrothermal crosslinking
      was used. The fraction of transmittance of the collagen films fabricated from
      insoluble collagen and soluble tropocollagen and glucose-mediated UV crosslinking
      was initially 0.91 +/- 0.02 and 0.98 +/- 0.01 for the smooth films and 0.90 +/-
      0.02 and 0.97 +/- 0.02 for the microgrooved films at 400 and 700 nm and was
      comparable to that of the native cornea, while the relaxed modulus and ultimate
      tensile strength ranged from 0.9 to 9.4 MPa and from 0.7 to 4.1 MPa,
      respectively, over the 3 weeks of culture and were initially at or below the
      range of values for the native cornea. These collagen scaffolds were
      significantly stronger and more transparent than previous scaffolds, and aligned
      stromal fibroblasts were observed on microgrooved surfaces.

PMID- 18333816
TI  - Characterization of porcine circulating progenitor cells: toward a functional
      endothelium.
AB  - The lack of available healthy vessels, significant patient morbidity, and high
      costs hinders the successful clinical utilization of autologous endothelial cells
      (ECs). Herein we assess the feasibility of using endothelial progenitor cells
      (EPC) found in circulating blood to engineer a functional endothelium on poly(1,8
      octanediol-co-citrate) (POC), a hemocompatible and biodegradable elastomer used
      in vascular tissue engineering. EPCs were isolated from porcine blood and
      biochemically differentiated into porcine endothelial (PE)-like cells in vitro.
      Once differentiated, EC phenotype and function on POC were assessed according to
      the presence of the EC-specific markers von Willebrand factor, platelet EC
      adhesion molecule, and vascular endothelial cadherin; metabolism of acetylated
      low-density lipoprotein; secretion of the anti-thrombogenic factors nitric oxide
      and prostacyclin; and inhibition of platelet adhesion and clotting processes in
      vitro. The effects of PE-like cells on porcine aortic smooth muscle cells
      (PASMCs) were also investigated via co-culture. PE-like cells on POC had
      phenotype, function, and clotting responses similar to those of primary aortic
      ECs. The presence of PE-like cells resulted in a 71 +/- 20% decrease in PASMC
      proliferation; a 52 +/- 2% decrease in the protein:deoxyribonucleic acid ratio;
      and an elongated, spindle-shaped morphology indicative of a shift from the
      proliferative to the contractile phenotype. These data suggest that EPCs and POC
      can provide the basis for a functional tissue-engineered endothelium.

PMID- 18333817
TI  - High-porosity poly(epsilon-caprolactone)/mesoporous silicon scaffolds: calcium
      phosphate deposition and biological response to bone precursor cells.
AB  - In this study, the fabrication and characterization of highly porous composites
      composed of poly(epsilon-caprolactone) and bioactive mesoporous silicon
      (BioSilicon) prepared using salt-leaching and microemulsion/freeze-drying methods
      are described. The role of silicon, along with porosity, in the scaffolds on
      calcium phosphate deposition was assessed using acellular in vitro calcification
      analyses. The presence of bioactive silicon in these scaffolds is essential for
      the deposition of calcium phosphate while the samples are immersed in simulated
      body fluid (SBF). Silicon-containing scaffolds produced using salt-leaching
      methods are more likely to calcify as a consequence of SBF exposure than those
      produced using microemulsion methods. In vitro proliferation and cell viability
      assays of these porous composites using human embryonic kidney fibroblast cells
      indicate that no cytotoxic effects are present in the scaffolds under the
      conditions used. Preliminary analyses of bone sialoprotein and alkaline
      phosphatase expression using orthopedically relevant mesenchymal cells derived
      from bone marrow suggest that such scaffolds are capable of mediating osteoblast
      differentiation. Overall, the results show that these porous silicon-containing
      polymer scaffolds enhance calcification, can be considered nontoxic to cells, and
      support the proliferation, viability, attachment, and differentiation of bone
      precursor cells.

PMID- 18333818
TI  - Semi-degradable scaffold for articular cartilage replacement.
AB  - Existing technologies have not met the challenge of designing a construct for the
      repair of focal cartilage defects such that it mimics the mechanical properties
      of and can integrate with native cartilage. Herein we describe a novel construct
      consisting of a non-degradable poly-vinyl alcohol (PVA) scaffold to provide long
      term mechanical stability, interconnected pores to allow for the infiltration of
      chondrocytes, and poly-lactic glycolic acid (PLGA) microspheres for the
      incorporation of growth factors to enhance cellular migration. The objective of
      this study was to characterize the morphological features and mechanical
      properties of our porous PVA-PLGA construct as a function of PLGA content.
      Varying the PLGA content was found to have a significant effect on the
      morphological features of the construct. As PLGA content increased from 10% to
      75%, samples exhibited a 6-fold increase in average percentage porosity, an
      increase in average microsphere diameter from 8 to 34 microm and an increase in
      average pore diameter from 29 to 111 microm. The effect of PLGA content on
      aggregate modulus and permeability was less profound. Our findings suggest that
      that morphology of the construct can be tailored to optimize cellular
      infiltration and the dynamic mechanical response. The experiments herein
      presented were conducted at the Hospital for Special Surgery.

PMID- 18333821
TI  - Locked versus unlocked plating with respect to plate length in an ulna fracture
      model.
AB  - OBJECTIVE: Determine contributions of plate length and locked fixation in an ulna
      fracture. METHODS: two groups of six pairs of ulnae were plated with a small
      fragment LCP around a 1 cm ostectomy. Control specimens: eight-hole plate, three
      consecutive unlocked screws on each side. Experimental specimens: 10-hole plate,
      two screws (Group 1, Unlocked; Group 2, Locked) in near- far configuration on
      either side. OUTCOMES: Stiffness in torsion and 4-point bending stiffness and
      load at yield. RESULTS: Unlocked: mean torsional stiffness (Ncm/deg) for the
      experimental and control specimens, 7.57 and 7.73, respectively (p > 0.05); mean
      bending stiffness (kN/m), 88.50 and 90.76, respectively (p > 0.05); and mean
      yield strength (kN), 1.06 and 0.89, respectively (p < 0.05). Locked: mean
      torsional stiffness for the experimental and control specimens, 7.10 and 8.27, re
      spectively (p > 0.05); mean bending stiffness, 72.96 and 79.20, respectively (p
      > 0.05); and mean yield strength, 1.23 and 1.03, respectively (p > 0.05). Mean
      differences between the experimental and control specimens in tor- sion:
      Unlocked, 0.17; Locked, 1.17 (p > 0.05). Mean differences in bending stiffness:
      Unlocked, 2.25; Locked, 6.24 (p > 0.05). Mean differences in yield strength:
      Unlocked, 0.17; Locked, 0.21 (p > 0.05). CONCLUSIONS: Locked plating provided no
      mechanical advantage over unlocked plating. The use of a longer plate with
      unlocked screws increased yield strength.

PMID- 18333820
TI  - Placenta-derived multipotent cells differentiate into neuronal and glial cells in
      vitro.
AB  - Stem cells have great potential for clinical application because of their self
      renewal property and ability to differentiate into many types of cells, but
      because there are ethical and biological limitations with current sources of stem
      cells, the search continues for more suitable sources of multipotent cells. We
      have reported previously on a population of multipotent cells isolated from the
      human term placenta, an ethically unproblematic and easily available source of
      tissue. These placenta-derived multipotent cells (PDMCs) can differentiate into
      lineages of mesenchymal tissues, including osteoblasts and adipocytes, as well as
      non-mesenchymal tissue of neuron-like cells. We further examined the ability of
      PDMCs to differentiate into all 3 types of neural cells--neurons, astrocytes, and
      oligodendrocytes--under various induction conditions, including retinoic acid
      (RA), 1-methyl-3-isobutylxanthine (IBMX), and co-culture with neonatal rat brain
      cells. PDMCs exhibited outgrowth of processes and the expression of neuron
      specific molecules such as neuron-specific enolase upon induction. Co-culture
      with neonatal rat brain cells also induced neural differentiation. Our results
      indicate that PDMCs can be differentiated into neural cell types of the human
      nervous system upon exposure to RA, IBMX, or primary rat brain cells.

PMID- 18333822
TI  - The quantification of the origin area of the deep forearm musculature on the
      interosseous ligament.
AB  - The diagnosis and treatment of injuries involving rupture of the interosseous
      ligament remain challenging. Few studies have considered the effects of rupture
      of the interosseous ligament on deep forearm muscle function. The objective of
      this study was to quantify the attachment areas of the deep forearm muscles on
      the interosseous ligament. The origins of the extensor indicis, extensor pollicis
      longus, extensor pollicis brevis, abductor pollicis longus, lexor pollicis
      longus, and lexor digitorum profundus were digitized from 11 cadavers. Three
      dimensional modeling techniques were used to quantify the origin area on bone and
      the interosse- ous ligament. The extensor pollicis longus and the abductor
      pollicis longus attached primarily to the interosseous liga- ment (81% and 62%,
      respectively). Although the other deep forearm muscles had larger origins on
      bone, relatively large areas on the interosseous ligament were observed, ranging
      from 31% to 47%. The muscle origins on the interosseous ligament were veriied
      histologically, where striated muscle originated directly from the dense
      connective tissue of the interosseous ligament. Due to their relatively large
      attach- ment areas on the interosseous ligament, the function of the deep forearm
      muscles might be altered after an interos- seous ligament rupture. Therefore,
      symptoms such as pain and weakness of the deep forearm muscles could serve as a
      basis for screening patients with injuries of the interosse- ous ligament.
      Furthermore, the data may help to elucidate factors limiting the healing of the
      interosseous ligament. Future studies should focus on quantifying the effect of
      an interosseous ligament rupture on the function of the deep forearm muscles and
      developing reconstructions that con- sider this function.

PMID- 18333823
TI  - MRI of tarsal coalition: frequency, distribution, and innovative signs.
AB  - OBJECTIVE: Tarsal coalition is uncommon, but not rare. Since it may present with
      chronic symptoms and since prior studies have shown that magnetic resonance (MR)
      has a high accu- racy for diagnosis, we evaluated the prevalence, frequency,
      location, and types of coalition, as well as secondary signs, as seen in a large
      clinical MR population. SUBJECTS AND METHODS: Initially a "word search" program
      was used to ind all diagnoses of "tarsal coalition" in our RIS database as part
      of 27,483 ankle MRIs performed over a ten-year period. We revaluated 101 of 169
      identiied cases for location (calca- neonavicular vs. talocalcaneal/subtalar) and
      type (osseous, cartilaginous, or ibrous, utilizing previously described MR
      criteria) of coalition. Additional imaging indings, including marrow edema and
      fractures, and associated secondary signs, such as talar "beaks," the "anteater"
      (hyperplastic anterior calcaneal process) sign, and the innovative "reverse
      anteater" (hyperplastic navicular) and "drunken waiter" (hypo/dysplastic
      sustentaculum tali) signs, were reported as well. As a second part to the study,
      in order to more ac- curately determine prevalence in a population requiring an
      MRI of the ankle, two observers reviewed 667 consecutive ankle MRIs performed on
      640 patients. Patients less than 12 years of age (N = 20, 3.0%) or with
      nondiagnostic exams (N = 73, 10.9%) were excluded. Note was made: 1. if a
      coalition was present, 2. if it was deinite or possible, 3. of the location, 4.
      of the type, 5. of secondary signs, and 6. the frequency of bilaterality.
      RESULTS: In the initial retrospective study, coalitions were identiied in 0.6% of
      exams performed, including 78 calcaneonavicular coalitions. Seven fractures were
      seen, all in the ibrous calcaneonavicular subgroup. We found only eight cases
      (10.3%) of the "anteater" sign, while identifying 19 cases (24.4%) of the
      "reverse" anteater sign in the calcaneonavicular group. Talar "beaks" were seen
      in 15 cases (19.2%) of the calcaneonaviuclar group and nine (39.1%) of the
      subtalar group. Sixteen (69.6%) of the subtalar cases demonstrated the "drunken
      waiter" sign, a dysplastic sustentaculum. We saw a dramatic difference in
      frequency of tarsal coalitions when we applied a prospec- tive approach; 11.5% of
      all patients (66/574) had a coali- tion, while 12.2% of studies (70/574)
      demonstrated tarsal coalitions: 25.7% (18/70) were subtalar, 71.4% (50/70) were
      calcaneonavicular, and 2.9% (2/70) had both. The calcaneonavicular coalitions
      were roughly evenly divided between the cartilaginous (56%) and ibrous (44%)
      subtypes, without any osseous coalitions being identiied. The subtalar coalitions
      were also nearly evenly divided between osse- ous/partially osseous (33.3%),
      cartilaginous (27.8%), and ibrous (38.9%). Talar "beaks" were seen in 25 cases
      (50%) of the calcaneonavicular group and ive (27.%) of the sub- talar group. We
      identiied six cases (12%) of the "anteater" and nine cases (18%) of the "reverse
      anteater" signs in our calcaneonavicular group. CONCLUSION: Tarsal coalitions ap-
      pear to be more common than previously described. This is likely to be because
      ibrous and cartilaginous coalitions are infrequently recognized by plain
      radiography. The frequency of tarsal coalitions may be as high as 11%. We also
      found a disproportionately higher relative frequency of calcaneo- navicular
      coalitions, either because subtalar coalitions are more subtle on MRI or because
      calcaneonavicular coalitions can be overly diagnosed. Calcaneonavicular
      coalitions tend to be overwhelmingly nonosseous, while there is a more even
      distribution for subtalar coalitions. Newly described signs, such as the "reverse
      anteater" and "drunken waiter," are commonly seen in calcaneonavicular and
      subtalar coali- tions, respectively.

PMID- 18333824
TI  - Bone plug versus suture fixation of the posterior horn in medial
      meniscalallograft transplantation: a biomechanical study.
AB  - This study was performed to determine if a meniscal al- lograft with attached
      bone plug and suture offers superior ixation when compared to allograft afixed
      with suture alone through a bony tunnel. Seven pairs of human cadaver proximal
      tibia specimens were obtained. The specimens were then randomly assigned to
      either Group 1 (suture alone) or Group 2 (bone plug plus suture). All Group 1
      specimens had the meniscus detached at the bony insertion of the anterior and
      posterior horns, with two No. 2 Ethibond sutures placed at the posterior root
      insertion. All Group 2 specimens had a posterior horn with a bone plug and two
      No. 2 Ethibond sutures. Both groups had their respective sutures passed through a
      7 mm tibial tunnel and secured over a screw and post on the proximal tibia. The
      specimens were then loaded to failure. The mean failure load for Group 1 was
      111.8 N (SD: 21 N) and for Group 2 was 112 N (SD: 32 N). Based on the Wilcoxon
      Rank-Sum analysis, the two groups were not signiicantly different. This study
      demonstrated no difference in the mean pullout strength of medial meniscal
      allograft posterior horn ixation between the two groups. This biome- chanical
      cadaveric study demonstrated that it may not be necessary to use an attached bone
      plug for medial meniscal transplant ixation, as using suture alone will sufice.
      The choice of using suture alone for the posterior horn meniscal attachment eases
      the technique of surgery when compared to using a bone plug plus suture.

PMID- 18333826
TI  - Management of flexor tendon injuries following surgical repair.

PMID- 18333825
TI  - The effects of alcohol on in-hospital mortality in drivers admitted after motor
      vehicle accidents.
AB  - BACKGROUND: The effects of alcohol on morbidity and mortality following motor
      vehicle accidents (MVAs) are controversial. This study was performed to address
      the effect of alcohol on in-hospital mortality for drivers in MVAs admitted to a
      trauma center before and after controlling for injury severity, safety device
      use, and patient demographics. METHODS: A retrospective study was performed using
      data from the National Trauma Data Bank, version 4.3. The cohort consisted of
      drivers in an MVA who were 15 years of age or older, had been admitted to the
      hospital on the same day as the accident, were screened for alcohol, and had no
      documentation of drugs in their system. Analyses were performed to explore the
      relationships between patient age, gender, race, presence of head injury,
      comorbid- ity status, injury severity score (ISS), and presence of alcohol and in
      hospital mortality. RESULTS: The cohort consisted of 67,021 patients, 38.3% of
      whom were drivers involved in an MVA and, following screening, were found to have
      alcohol present in their system. Drivers who had alcohol present were more likely
      to be younger, male, White, not using a safety device, and to have sustained a
      head injury, than drivers who had no alcohol present in their system (alcohol
      absent driv- ers) at hospital presentation. After controlling for potential
      confounding variables, risk factors for in-hospital mortality included male sex,
      older age, and higher injury severity, while protective factors included the
      presence of alcohol and use of safety devices. The single strongest predictor of
      mortality was ISS. Sensitivity analyses to relect the impact of inlation in true
      ISS scores in the subgroup of patients who had alcohol present as well as a head
      injury revealed that the protective effect of alcohol diminished and became
      nonsignificant when the ISS was reduced by 9% and became a significant risk
      factor for in-patient mortality when the false elevation in ISS was estimated at
      21%. CONCLUSIONS: These results suggest the importance of carefully considering
      the consequences that falsely inlated ISS scores might have for patients with
      alcohol present. Future work should evaluate the possible inlation of ISS and
      attempt to reconcile different interpreta- tions of the effects that the presence
      of alcohol may have on MVA mortality based by jointly considering crash site and
      in-hospital data.

PMID- 18333827
TI  - Psoriatic arthritis and arthroplasty: a review of the literature.
AB  - Psoriatic arthritis is an inflammatory arthropathy as- sociated with the
      characteristic dermatologic lesions of psoriasis. The diagnosis of psoriatic
      arthritis is quite difficult, due to the overlap of patients with osteoarthritis
      (OA) or rheumatoid arthritis (RA) with concomitant non-associated psoriasis. A
      nonspecific elevation in inflammatory markers (erythrocyte sedimentation rate,
      ESR; antinuclear antibodies, ANA; or rheumatoid factor, RF) and characteristic
      radiographic features are often present in these patients. The mainstay of
      treatment is medical management, using NSAIDs, various immunosuppressants, and
      anti-TNF agents, for both pain control and possibly as disease modifying agents.
      Only a minority of patients require surgical intervention, leading to the limited
      amount of literature concerning total joint arthroplasty and psoriatic arthritis.
      While past literature has yielded high infection rates post-arthroplasty, newer
      studies have found more promising results. Alternative surgical options for
      treating destructive arthritis include open or arthroscopic synovectomy. While
      early results are promising, recurrence rates and long-term outcomes are not yet
      available.

PMID- 18333828
TI  - Primary leiomyosarcoma of the proximal tibia: case report and review of the
      literature.

PMID- 18333829
TI  - A broken scalpel blade tip: an unusual complication of knee arthroscopy.
AB  - The case of a patient is presented in whom a No. 11 scalpel blade was
      inadvertently broken and embedded within the lateral femoral condyle during
      initial arthroscopic portal creation. After a thorough diagnostic arthroscopy and
      synovectomy to expose the distal femoral articular surface was unsuccessful,
      luoroscopy was performed to localize the blade fragment in orthogonal planes. The
      blade tip was eventually retrieved from its position below the surface of the
      cartilage. The details of the loss and recovery of the blade fragment reinforce
      that exceptional care must be taken and attention given during the creation of
      portals, particularly when resistance is encountered. Additionally, all
      instruments, especially scalpel blades, should be exam- ined carefully when
      removed from the knee joint.

PMID- 18333830
TI  - Isolated trapezoid fractures: a case report with compilation of the literature.
AB  - Isolated fractures of the trapezoid bone have been rarely reported in the
      literature, the mechanism of injury being an axial or bending load transmitted
      through the second metacarpal. We report a case of an isolated, nondisplaced
      trapezoid fracture that was sustained by direct trauma and subsequently treated
      successfully in a short-arm cast. Diagnostic and treatment strategies for
      isolated fractures of the trapezoid bone are reviewed as well as the results of
      operative and nonoperative treatment.

PMID- 18333831
TI  - Multiple neurilemomas in the upper extremity: a series of three cases.
AB  - Neurilemomas are the most frequently arising benign nerve tumors of the upper
      extremity and are also called Schwannomas. Generally, they present as solitary
      tumors, although multiple tumors are common. Regardless of number, they are
      usually found on the lexor surface of the forearm and hand, and multiple tumors
      are almost always located within a single major nerve, its branches, or both. We
      present three patients who had multiple neurilemomas; two patients had tumors
      within a single major nerve and its branches, and the third patient had an
      unusual occurrence of one tumor in the ulnar nerve and a second tumor in a branch
      of the median nerve.

PMID- 18333832
TI  - Use of an Ilizarov fixator for deformity correction prior to revision knee
      arthroplasty.
AB  - Malalignment is associated with an increased rate of loosening of knee
      prostheses. We present a case of primary knee replacement failure due to pre
      existing tibial deformity. Correction of the deformity and associated
      malalignment was undertaken using the Ilizarov osteotomy method prior to full
      knee revision surgery.

PMID- 18333833
TI  - Simultaneous bilateral distal biceps tendon rupture during a preacher curl
      exercise: a case report.
AB  - Complete rupture of the distal biceps tendon is a rare injury, the overwhelming
      majority occurring in the dominant arm of males during the fourth to sixth
      decades of life. Simultaneous bilateral rupture of the distal biceps tendon is an
      extremely rare occurrence, with only three cases reported in the literature. This
      unusual injury occurred in a recreational weightlifter during a preacher curl
      exercise. In this particular case, a 6-week delay in presentation necessitated a
      staged procedure in which a primary repair was feasible in one elbow, while
      reconstruction using allograft tissue was required in the contralateral elbow.
      Satisfactory results for both elbows were achieved, with return to weightlifting
      by one year following surgery.

PMID- 18333834
TI  - Ca2+ signalling: a new route to NAADP.
AB  - NAADP (nicotinic acid-adenine dinucleotide phosphate) is a derivative of NADP
      (nicotinamide-adenine dinucleotide phosphate), which differs by the presence of a
      nicotinic acid instead of a nicotinamide moiety. This small structural difference
      makes NAADP one of the most powerful second messengers known, able to mobilize
      intracellular Ca2+ in a wide range of cellular models, ranging from invertebrates
      to mammals. Despite this, our understanding of NAADP homoeostasis, metabolism and
      physiological action is still limited. A new report by Vasudevan and colleagues
      in this issue of the Biochemical Journal provides important new data by
      describing a new synthetic activity in sperm cells which may turn out to
      represent the most physiologically relevant route to this second messenger.

PMID- 18333835
TI  - Liver fibrosis.
AB  - Liver damage leads to an inflammatory response and to the activation and
      proliferation of mesenchymal cell populations within the liver which remodel the
      extracellular matrix as part of an orchestrated wound-healing response. Chronic
      damage results in a progressive accumulation of scarring proteins (fibrosis)
      that, with increasing severity, alters tissue structure and function, leading to
      cirrhosis and liver failure. Efforts to modulate the fibrogenesis process have
      focused on understanding the biology of the heterogeneous liver fibroblast
      populations. The fibroblasts are derived from sources within and out with the
      liver. Fibroblasts expressing alpha-smooth muscle actin (myofibroblasts) may be
      derived from the transdifferentiation of quiescent hepatic stellate cells. Other
      fibroblasts emerge from the portal tracts within the liver. At least a proportion
      of these cells in diseased liver originate from the bone marrow. In addition,
      fibrogenic fibroblasts may also be generated through liver epithelial (hepatocyte
      and biliary epithelial cell)-mesenchymal transition. Whatever their origin, it is
      clear that fibrogenic fibroblast activity is sensitive to (and may be active in)
      the cytokine and chemokine profiles of liver-resident leucocytes such as
      macrophages. They may also be a component driving the regeneration of tissue.
      Understanding the complex intercellular interactions regulating liver
      fibrogenesis is of increasing importance in view of predicted increases in
      chronic liver disease and the current paucity of effective therapies.

PMID- 18333836
TI  - Early spontaneous recanalization following acute carotid occlusion.
AB  - BACKGROUND AND PURPOSE: Occlusion of the internal carotid artery (ICA) and stroke
      may be the consequence of either local thrombosis due to atherosclerosis or
      massive embolism. Up to date, there are only few reports of subsequent
      recanalization. METHODS: We report 12/76 cases of acute ICA occlusion leading to
      ischemic stroke, in which early recanalization was identified. Ultrasound and
      stroke MRI findings, therapeutic options, and outcome are described. RESULTS:
      10/12 patients showed an- or hypoechogenic morphology of occlusion. While in 7/12
      cases complete recanalization was seen, in 5/12 patients partial recanalization
      with filiform flow (4) or residual high-grade stenosis (1) was detected. 10/12
      patients had territorial or subcortical infarction, while two showed small
      cortical lesions only. In 7/12 cases, a potential cardiac source of embolism was
      found. Five patients received tPA; four patients underwent early carotid
      endarterectomy of the partially recanalized ICA within 48 hours. In the 10-day
      follow-up examination 10/12 patients showed clinical improvement as measured by
      the NIHSS. CONCLUSIONS: Spontaneous recanalization after occlusion of the ICA may
      occur and might be more frequent than hitherto assumed. Echogenicity analysis and
      serial examinations of symptomatic ICA occlusion is useful for identifying a
      patient subgroup that might benefit from further therapy.

PMID- 18333837
TI  - Proton magnetic resonance spectroscopy detects a relative decrease of N
      acetylaspartate in the hippocampus of patients with dementia with Lewy bodies.
AB  - BACKGROUND AND PURPOSE: To characterize the cerebral metabolic changes in
      dementia with Lewy bodies patients. METHODS: The metabolic ratios of NAA/Cr and
      Cho/Cr in bilateral hippocampus were determined by proton magnetic resonance
      spectroscopy in 8 patients and 8 age-matched healthy controls. RESULTS: Dementia
      with Lewy bodies patients showed significantly lower NAA/Cr ratios in bilateral
      hippocampus, while the Cho/Cr ratio did not differ from the control group.
      CONCLUSIONS: Our data show relatively decrease of N-acetylaspartate in the
      hippocampus of patients with early or intermediate stage DLB. Hence, damage of
      neurons seems to be an early alteration in DLB.

PMID- 18333838
TI  - Cutting balloon angioplasty for carotid in-stent restenosis: case reports and
      review of the literature.
AB  - Percutaneous stenting techniques are becoming more commonly used for treatment of
      carotid artery disease. One outcome of particular concern is in-stent restenosis.
      Indications for treatment of in-stent restenosis are not clearly defined. Use of
      traditional balloon angioplasty with or without stent placement is still
      considered the first option. Cutting balloon angioplasty has recently been used
      as an alternative treatment option for revascularization of in-stent restenosis
      with higher procedural success rates and without the use of additional stents. We
      report our experience with cutting balloon angioplasty in treating 2 patients
      with carotid in-stent restonosis, and review previous cases reported in the
      literature. A total of 16 patients have been treated with cutting balloon
      angioplasty. Among 11 patients for whom the clinical and angiographic information
      were available, 63% of patients were asymptomatic at the time of treatment, and
      more than 90% of patients showed either complete angiographic resolution or
      residual stenosis of less than 30%. Additional stent placement or angioplasty was
      required in only half of the patients, and 1 patient had recurrent stenosis. The
      review suggests that the procedure is safe and effective.

PMID- 18333839
TI  - Detection of right-to-left shunts: comparison between the International Consensus
      and Spencer Logarithmic Scale criteria.
AB  - BACKGROUND: International Consensus Criteria (ICC) consider right-to-left shunt
      (RLS) present when Transcranial Doppler (TCD) detects even one microbubble
      (microB). Spencer Logarithmic Scale (SLS) offers more grades of RLS with
      detection of >30 microB corresponding to a large shunt. We compared the yield of
      ICC and SLS in detection and quantification of a large RLS. SUBJECTS AND METHODS:
      We prospectively evaluated paradoxical embolism in consecutive patients with
      ischemic strokes or transient ischemic attack (TIA) using injections of 9 cc
      saline agitated with 1 cc of air. Results were classified according to ICC
      [negative (no microB), grade I (1-20 microB), grade II (>20 microB or "shower"
      appearance of microB), and grade III ("curtain" appearance of microB)] and SLS
      criteria [negative (no microB), grade I (1-10 microB), grade II (11-30 microB),
      grade III (31100 microB), grade IV (101300 microB), grade V (>300 microB)]. The
      RLS size was defined as large (>4 mm) using diameter measurement of the septal
      defects on transesophageal echocardiography (TEE). RESULTS: TCD comparison to TEE
      showed 24 true positive, 48 true negative, 4 false positive, and 2 false negative
      cases (sensitivity 92.3%, specificity 92.3%, positive predictive value (PPV)
      85.7%, negative predictive value (NPV) 96%, and accuracy 92.3%) for any RLS
      presence. Both ICC and SLS were 100% sensitive for detection of large RLS. ICC
      and SLS criteria yielded a false positive rate of 24.4% and 7.7%, respectively
      when compared to TEE. CONCLUSIONS: Although both grading scales provide agreement
      as to any shunt presence, using the Spencer Scale grade III or higher can
      decrease by one-half the number of false positive TCD diagnoses to predict large
      RLS on TEE.

PMID- 18333840
TI  - The reformed International Council for Standardization in Hematology (ICSH).

PMID- 18333841
TI  - Clinical, laboratory and therapeutic aspects of platelet-type von Willebrand
      disease.
AB  - Platelet-type von Willebrand disease (PT-VWD), or pseudo-VWD, is a rare inherited
      platelet disorder characterized by an increased affinity of the platelet membrane
      glycoprotein Ibalpha receptor for normal von Willebrand factor leading to
      characteristic platelet hyperaggregability. As PT-VWD shares most of the clinical
      and laboratory features of subtype 2B VWD, the differential diagnosis between
      these two inherited bleeding disorders requires either platelet-mixing or
      molecular genetic studies. In this review, the main clinical, laboratory and
      therapeutic characteristics of PT-VWD are concisely reported.

PMID- 18333842
TI  - ICSH Guideline for worldwide point-of-care testing in haematology with special
      reference to the complete blood count.
AB  - These guidelines provide information on how to develop and manage a point-of-care
      (POCT) service so that reliable haematology results are produced regardless of
      where the test is performed. Many of the issues addressed here are relevant to
      POCT within hospitals or health centres; however, the principles are equally
      applicable to care in the community and doctors' offices. Other aspects discussed
      in this guideline are the initiation of the service (including indications for
      and limitations of a POCT service), staff training, type of haematology equipment
      selected, the blood results, monitoring of quality, accreditation, safety and
      cost. Equipment selected should generate results that are comparable to those of
      the local reference laboratory. If a complete independent evaluation of the POCT
      device has not been performed, the purchaser should perform a local assessment
      according to the protocol in this document. A literature search should also be
      undertaken to find independent peer reviewed evaluations on POCT equipment. Often
      the ideals discussed here may not be achievable in some developing countries but
      long-term training and education of POCT workers needs to be supported and
      constantly kept on government agendas to reach the recommendations advised here.
      Users should interpret these recommendations for their particular POCT needs and
      setting.

PMID- 18333843
TI  - Prognostic value of platelet indices as determined by ADVIA 120 in patients
      suspected of having disseminated intravascular coagulation.
AB  - Recent technological advances have made it possible to record a variety of
      platelet indices using automated hematology analyzers. Disseminated intravascular
      coagulation (DIC) is associated with the dramatic hemostasis activation, with
      evidence of fibrin formation and platelet consumption. We investigated the
      prognostic significance of platelet indices as measured by ADVIA in 222 patients
      suspected of having DIC. The presence of overt DIC was defined using the scoring
      system of the International Society of Thrombosis and Haemostasis Subcommittee.
      Twenty-eight day hospital mortality was used as a clinical prognosis parameter.
      Median platelet count and platelet-crit (PCT) levels markedly decreased in
      nonsurvivors, whereas mean platelet volume (MPV), platelet component distribution
      width (PCDW) and platelet dry mass distribution width (PMDW) were significantly
      increased in nonsurvivors. In terms of ROC analysis, which was conducted to
      predict 28-day mortality, areas under the receiver operating characteristic curve
      (AUC) were; 0.73 platelet count, 0.72 for PCT, 0.69 for PCDW, 0.65 for PMDW and
      0.61 for MPV. The odds ratio of a reduced platelet count for the relative risk of
      28-day mortality was 5.249 (95% CI: 2.399-11.486), and the odds ratio for PCDW
      was 3.240 and for PMDW 3.262. Among these indices, platelet count, PCDW and PMDW
      were found to be more predictive of 28-day hospital mortality. Our results
      suggest that these indices may provide prognostic information on hospital
      mortality in the patients suspected of having DIC.

PMID- 18333844
TI  - A strategy of splitting individual high volume cord blood units into two half
      subunits prior to processing increases the recovery of cells and facilitates ex
      vivo expansion of the infused haematopoietic progenitor cells in adults.
AB  - This study was designed to maximize the recovery of the desirable cell
      populations contained in the cord blood (CB) freezing bag, in order to optimize
      donor selection for adolescents and adults. To evaluate this hypothesis, high
      volume CB units (CBUs) were categorized into three volume collection groups (120
      139, 140-159 and >or=160 ml) and were randomly split before volume reduction into
      two half low volume CBUs; (a) and (b). Using the SEPAX Cell Processing System,
      all CBUs were standardized to 26 ml. In 128 high volume split CBUs, the WBC,
      mononuclear cell and CD34+ cell recoveries were significantly higher (P <or=
      0.05; 80%, 79.89% and 87.41% respectively) than those of the 106 high volume
      nonsplit CBUs (59.7%, 62.82% and 68.62% respectively), resulting in significantly
      higher (P <or= 0.05) mean weights of the potential recipients. The strategy of
      splitting high volume CBUs into two half low volume CBUs improves the recovery of
      the cells and is an attractive option for ex vivo expansion, in order to
      facilitate the CB transplantation in adults who are not eligible for single CB
      transplantation because of limitations of cell dose.

PMID- 18333845
TI  - Aberrant co-expression of CD19 and CD56 as surrogate markers of acute myeloid
      leukemias with t(8;21) in Taiwan.
AB  - Aberrant antigen expression in acute myeloid leukemia (AML) has been extensively
      studied in the West with limited reports from Taiwan. We carried out this
      retrospective study to characterize the frequency and significance of aberrant
      antigen expression of AML in Taiwan. Among 111 cases, 58 (52%) showed aberrant
      antigen expression, most frequently CD7 (27%) and CD56 (23%). Aberrant CD7
      expression was observed in all non-AML-M3 subtypes, most frequently in AML-M7
      (4/6, 67%); while CD19 expression was only observed in AML-M2 (5/36, 14%). CD56
      expression was most common in AML-M5 (4/8, 50%). The relative frequency of CD19
      and CD56 expression in AML with t(8;21) was higher than those with other
      chromosomal abnormalities or normal karyotype (P = 0.011 and 0.005,
      respectively). In non-M3 AML, aberrant antigen expression was identified in 56/96
      (58%) cases, in contrast to 2/15 (13%) AML-M3 cases (P = 0.001). CD7, CD19 and
      CD56 expression was not correlated with remission rate. We concluded that
      aberrant immunophenotype was more frequent in non-M3 leukemias in Taiwan. The
      relative frequency of CD19 and/or CD56 expression in AML with t(8;21) was
      significantly higher than those without this translocation and co-expression of
      these two antigens may serve as the surrogate markers for AML with t(8;21).

PMID- 18333846
TI  - Distinct locomotive patterns of granulocytes, monocytes and lymphocytes in a
      stable concentration gradient of chemokines.
AB  - The pattern of leukocyte locomotion can be changed in many pathological
      situations, but its accurate analysis is difficult because of technological
      limitation. In the present study, by using a newly developed time-lapse
      videomicroscopic technique, we have analyzed the locomotive patterns of
      leukocytes in a stable concentration gradient of chemokines. Granulocytes,
      monocytes, and lymphocytes were purified from adult human peripheral blood.
      Locomotive behavior of the leukocytes was analyzed by an optical assay using a
      microchannel producing a stable concentration gradient of chemokines.
      Videomicroscopic analysis showed distinct locomotive patterns of granulocytes,
      monocytes, and lymphocytes. Granulocytes were intrinsically motile, vigorously
      moving in random direction without any chemokine stimulation. Upon stimulation
      with CXCL8/IL-8, the speed of migration was increased from 13.3 +/- 2.8 to 19.4
      +/- 2.5 microm/min (P = 0.002, n = 100) and they moved toward the chemokine,
      although many cells still wandered very much. Stimulation with CCL5/RANTES or
      CXCL12/SDF-1alpha induced similar changes in locomotive pattern. On the other
      hand, most lymphocytes did not polarize or move spontaneously without chemokine
      stimulation. Stimulation with CXCL12 induced directional migration in 37% of the
      lymphocytes at a speed of 9.6 +/- 1.6 microm/min (n = 100). The movement pattern
      of monocytes was similar to that of granulocytes in that they tend to become
      polarized and move spontaneously, but they moved at a very slow speed ranging
      from 3.9 to 4.2 microm/min even with chemokine stimulation. The new optical assay
      may be useful for many diagnostic as well as basic studies.

PMID- 18333847
TI  - ZAP-70 is highly expressed in most cases of childhood pre-B cell acute
      lymphoblastic leukemia.
AB  - The tyrosine kinase ZAP-70 plays a critical role in signal transduction in T
      cells and NK cells but has limited expression in primary human B cells. ZAP-70
      is, however, expressed in adult B cell chronic lymphocytic leukemia where it
      correlates with a poor prognosis. We wished to determine if ZAP-70 is also
      expressed in pediatric B cell malignancy. A quantitative PCR assay for ZAP-70
      expression was established and ZAP-70 expression in a range of human B cell lines
      was compared with expression in the Jurkat T cell line. ZAP-70 expression was
      then determined in bone marrow lymphoblasts obtained from 12 patients with pre-B
      cell acute lymphoblastic leukemia (ALL). ZAP-70 expression was not detected in
      mature B cell lines but was detected in pre-B cell lines at a level comparable to
      that seen in T cells. ZAP-70 expression was strongly expressed in nine of the 12
      cases of primary pre-B cell lymphoblastic leukemia. The T cell-associated protein
      kinase ZAP-70 is highly expressed in pre-B lineage cells and most cases of pre-B
      acute lymphoblastic leukemia. ZAP-70 expression may hold prognostic value for pre
      B ALL and raises the prospect of a novel therapeutic target.

PMID- 18333848
TI  - Hematological parameters and anaerobic threshold in Brazilian soccer players
      throughout a training program.
AB  - We assessed the responses of hematological parameters and their relationship to
      the anaerobic threshold of Brazilian soccer players during a training program.
      Twelve athletes were evaluated at the beginning (week 0, T1), in the middle (week
      6, T2), and at the end (week 12, T3) of the soccer training program. On the first
      day at 7:30 am, before collecting the blood sample at rest for the determination
      of the hematological parameters, the athletes were conducted to the
      anthropometric evaluation. On the second day at 8:30 am, the athletes had their
      anaerobic threshold measured. Analysis of variance with Newman-Keuls'post hoc was
      used for statistical comparisons between the parameters measured during the
      soccer training program. Correlations between the parameters analyzed were
      determined using the Pearson's correlation coefficient. Erythrocytes
      concentration, hemoglobin, and hematocrit were significantly increased from T1 to
      T2. The specific soccer training program led to a rise in erythrocytes,
      hemoglobin, and hematocrit from T1 to T2. We assumed that these results occurred
      due to the plasma volume reduction and may be explained by the soccer training
      program characteristics. Furthermore, we did not observe any correlation between
      the anaerobic threshold and the hematological parameters.

PMID- 18333849
TI  - Malignancies in beta-thalassemia patients: a single-center experience and a
      concise review of the literature.
AB  - Thalassemia represents the world's most common monogenic disease, characterized
      by absence of or decreased globin chain production. The lifespan of thalassemia
      patients has been extended as a result of current supportive treatment. We report
      three cases of cancer (non-Hodgkin lymphoma, Hodgkin disease, and seminoma) in
      thalassemic patients. Factors that may contribute to the pathogenesis of cancer
      seem to be infections and iron overload through mechanisms of oxidative damage;
      immunomodulation or coexistence of the two diseases may only be coincidental.

PMID- 18333850
TI  - Primary prophylaxis with voriconazole in patients receiving induction
      chemotherapy on the MRC adult acute lymphoblastic leukaemia trial (UK-ALL XII) to
      avoid itraconazole-enhanced vinca neurotoxicity.

PMID- 18333852
TI  - Oocyte morphometry in female dogs (Canis familiaris, Linnaeus, 1758).
AB  - In the present study, the ovaries of 15 healthy bitches divided into three groups
      according to age were analysed by histology and morphometry: group 1 (1-3 years),
      group 2 (>3-5 years) and group 3 (>5-7 years). After ovariosalpingohysterectomy,
      the ovaries were fixed, routinely processed for embedding in paraffin and stained
      with haematoxylin-eosin. The following morphometric parameters were analysed:
      maximum and minimum diameter (microm), perimeter (microm), area (microm(2)) and
      roundness of the cytoplasm and nucleus of oocytes from different types of
      follicles. Significant differences in the cytoplasmic and nuclear parameters of
      follicular oocytes between the experimental groups were determined by anova and
      the Tukey test (5%). For the biotechnology of reproduction, the present results
      showed that in vitro maturation yielded the best performance for oocytes from
      primordial follicles in group 3 females and for oocytes embedded in secondary and
      tertiary follicles in group 2 females. In addition, the present findings will
      help in the diagnosis and prognosis of diseases affecting bitches, and will
      especially contribute to a better understanding of these cells by researchers in
      the field of histology and canine reproduction.

PMID- 18333853
TI  - Effects of betamethasone treatment on central myelination in fetal sheep: an
      electron microscopical study.
AB  - The long-term effect of betamethasone on the myelination of commissural and
      associational fibres was investigated in fetal sheep. We studied the corpus
      callosum and subcortical white matter by electron microscopy. Axons were
      subdivided into classes according to their axonal diameter: class I: < or =0.65
      microm; class II: 0.66-0.84 microm; class III: > or =0.85 microm. Under control
      conditions, the different functions of the white matter tracts examined were
      reflected by three morphological criteria: (1) there was a diverse percentage of
      axonal classes in the investigated areas. In corpus callosum the axons of class
      II predominate (47.1%). In the subcortical white matter, class I axons with small
      diameter are in majority (40.8%). (2) In the subcortical white matter more axons
      are present, with especially large diameter and hence of axonal class III. (3)
      The axons of subcortical white matter have thicker myelin sheaths than those of
      the corpus callosum. Betamethasone administration caused a significant decrease
      of class II axons in the corpus callosum (36.9%). In corpus callosum, axons of
      all classes present thicker myelin sheaths. Betamethasone administration resulted
      in a change in the formation of the myelin sheath in the commissural fibres of
      the corpus callosum but not in the associational fibres of the subcortical white
      matter. This could be the morphological correlate to behavioral and cognitive
      changes known to occur in humans after prenatal glucocorticoid treatment.

PMID- 18333854
TI  - Effects of castration on the expression of TrkB and p75NTR in the vas deferens
      and male accessory genital glands of the rat.
AB  - Brain-derived neurotrophic factor (BDNF) is a growth factor belonging to the
      family of neurotrophins. Neurotrophins exert their effects by binding to
      corresponding receptors, which are formed by the tyrosine receptor kinases TrkA,
      TrkB and TrkC, and the low-affinity p75NTR receptor. The role of neurotrophins in
      the biology of male genital organs is far from clear. In particular, little is
      known about the influence of sex hormones on the expression of neurotrophin
      receptors. In the present study, using immunohistochemistry, we investigated the
      distribution of TrkB and p75NTR in the vas deferens and accessory male genital
      glands in normal and castrated rats. In normal rats, both TrkB and p75NTR
      immunoreactivities were localized in the epithelial layer of the vas deferens and
      prostate gland. The nerves were immunoreactive in all the examined organs.
      Castration induced the loss of both TrkB and p75NTR immunoreactivities in the
      epithelial layer. On the contrary, both receptors persisted or, as in the case of
      p75NTR, increased in the nerves after castration. These results show that
      receptors that bind BDNF are expressed in the internal male genital organs of the
      rat and that their expression is differently regulated by androgen hormones. It
      can be hypothesized that BDNF, via interacting with p75NTR, has a role in the
      castration-induced regression of the sympathetic nerves.

PMID- 18333855
TI  - Histology and ultrastructure of the developing superficial digital flexor tendon
      in rabbits.
AB  - This study was designed to investigate the developmental changes in the
      superficial digital flexor tendon (SDFT) of the white New Zealand rabbit, from 5
      to 7 days pre-natal to 112 days post-natal (PN), at histological and
      ultrastructural levels. The tendons changed from being highly cellular with 13079
      +/- 2538 cell/mm(2) and little directional organization to a longitudinally
      oriented, predominantly connective tissue structure with relatively few, mature
      tenocytes (2384 +/- 365 cell/mm(2)). Fibrillogenesis was seen in isolated
      vacuoles of fibroblast cytoplasm during fetal life as well as after birth, but
      less frequently with increasing age. At the ultrastructural level, there was a
      progressive increase in the mean diameter of collagen fibrils with age throughout
      the population, until PN day 28. A bimodal distribution of collagen fibril size
      was first observed on PN day 56 while at day 112, the fibrils were fully
      differentiated and showed a multimodal size distribution. The development of
      elastic fibres preceded that of collagen fibres and accompanied progressively
      more marked sinusoidal crimping in collagen fibres on PN days 7 and 14. The
      tendons of older animals became less tightly crimped. The cells of the epi- and
      endotenon were less mature and relatively undifferentiated compared with the
      cells in the body of the tendon of the same age, which might explain their
      ability to initiate healing of tendon injuries in older animals. In conclusion,
      extensive changes were observed in tendons during growth and maturation, with
      diameters of collagen fibrils, tissue orientation and cellularity being the
      parameters affected, probably due largely to increased physical activity.

PMID- 18333856
TI  - The development of the digestive tract in larval European catfish (Silurus glanis
      L.).
AB  - The European catfish, Silurus glanis L., has become an important aqua cultural
      fish in Croatia, and it is cultivated extensively in ponds in polyculture with
      carps. The development of the digestive tract in S. glanis was studied with the
      aim of improving intensive fish production. Research was carried out on S. glanis
      larval stadium from 1- to 19-day post-hatching (DPH). The main histological
      methods used were: haematoxylin and eosin staining, periodic acid Schiff staining
      (PAS), Alcian blue (AB) and toluidin blue staining (TB). A yolk sac was present
      during the first 5 days (1-5-DPH). During the initial 3-DPH period, there was no
      trace PAS and AB activity in the digestive tract. Differentiation of the
      digestive tract began at 3- to 5-DPH. The oesophagus was positive for AB at 5
      DPH, PAS and TB after 7-DPH. Differentiation of enterocytes began at 5-DPG and
      the intestines were complete at 11-DPH. Development of liver and pancreas was
      also studied. The analysis of data obtained in this study suggests that after 5
      DPH catfish larvae have morphologically completed digestive tracts.

PMID- 18333857
TI  - Changes in the myosin heavy chain 2a and 2b isoforms of the anterior belly of the
      digastric muscle before and after weaning in mice.
AB  - During the process of growth and development, the digastric muscle is subjected
      to marked functional changes, including the change from suckling to mastication.
      In particular, because the anterior belly of the digastric muscle, which is one
      of the suprahyoid muscles, plays an important role in mastication. Therefore,
      this muscle seems to undergo a marked functional change before and after weaning.
      However, the details remain unknown. Here, to clarify the changes in the muscle
      fibre characteristics of the anterior belly of the digastric muscle before and
      after weaning, we examined myosin heavy chain isoforms at the protein
      (immunohistochemistry) and mRNA (transcription) levels. As a control, the changes
      in the muscle fibre characteristics of the sternohyoid muscle, which is
      anatomically aligned in the same direction as the anterior belly of the digastric
      muscle, were analyzed. The results showed that, in the anterior belly of the
      digastric muscle that is involved in mandibular movements in mice, the ratio of a
      fast-contraction isoform with strong contractile force increased after weaning.
      We believe that this occurred in response to a functional change from suckling to
      mastication. On the other hand, there was little change in the composition of
      sternohyoid muscle.

PMID- 18333858
TI  - Minimising harm: human variation and adverse drug reactions (ADRs).

PMID- 18333859
TI  - A natural approach to treatment of inflammatory bowel disease.

PMID- 18333860
TI  - A review of the clinical pharmacology of maraviroc. Introduction.

PMID- 18333861
TI  - Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel
      CCR5 antagonist, in healthy volunteers.
AB  - AIMS: To evaluate the pharmacokinetics, safety and tolerability of single and
      multiple oral doses of maraviroc in healthy volunteers. METHODS: Three double
      blind, placebo-controlled, dose-escalation studies with either single or multiple
      doses of maraviroc were conducted in healthy volunteers. Plasma and urine samples
      were collected to investigate the pharmacokinetics of maraviroc and evaluate any
      changes with respect to dose and duration/frequency of dosing. Safety and
      toleration of maraviroc were also assessed. RESULTS: Maraviroc is rapidly
      absorbed following oral administration, and plasma T(max) is achieved within 0.5
      4.0 h postdose. Steady-state plasma concentrations are achieved after 7
      consecutive days of dosing. Although the pharmacokinetics of maraviroc is
      nonproportional over the dose range studied (3-1200 mg), the degree of
      nonproportionality is small at clinically relevant doses. Renal clearance is
      approximately 10-12 l h(-1) and appears unaffected by increasing maraviroc doses.
      Maraviroc does not significantly modulate the activity of CYP2D6 or CYP3A4 at
      clinically relevant doses. There were no serious adverse events in any of these
      studies, and doses up to 900 mg were generally well tolerated, with postural
      hypotension being the dose-limiting event. There was no pattern or dose
      relationship observed with maraviroc with regard to laboratory abnormalities,
      including hepatic transaminases. No clinically significant increases in QTc were
      noted at clinically relevant doses. CONCLUSIONS: Maraviroc is absorbed into the
      systemic circulation and reaches steady state by day 7 of multiple dosing. It
      does not significantly influence the activity of major drug-metabolizing enzymes
      and is well tolerated at clinically relevant doses, with most adverse events
      being mild or moderate.

PMID- 18333862
TI  - Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine,
      and ethinyloestradiol/levonorgestrel in healthy volunteers.
AB  - AIMS: To assess the effect of maraviroc on the pharmacokinetics of midazolam, a
      sensitive probe CYP3A4 substrate; lamivudine/zidovudine, a combination of
      nucleoside reverse transcriptase inhibitors (NRTIs); and
      ethinyloestradiol/levonorgestrel, a combination oral contraceptive. METHODS:
      Three randomized, double-blind, placebo-controlled studies were conducted in
      healthy subjects to assess the effect of maraviroc on pharmacokinetics of other
      drugs. Two, two-period crossover studies were conducted to assess (i) the effect
      of steady-state maraviroc (300 mg b.i.d.) on pharmacokinetics of midazolam; and
      (ii) the effect of steady-state maraviroc (300 mg b.i.d.) on the pharmacokinetics
      of lamivudine/zidovudine. A third two-way crossover study was conducted to
      evaluate the effect of steady-state maraviroc (100 mg b.i.d.) on the
      pharmacokinetics of 30 microg ethinyloestradiol/150 microg levonorgestrel
      (Microgynon). RESULTS: The geometric mean ratios for C(max) and AUC for each of
      the compounds tested in the presence and absence of maraviroc were between 92%
      and 121%. There were no notable differences in T(max), t(1/2) or CL(R) (where
      measured) for any of the compounds. CONCLUSIONS: Maraviroc had no clinically
      relevant effects on the pharmacokinetics of the CYP3A4 substrate midazolam, the
      NRTIs zidovudine/lamivudine, or the oral contraceptive steroids ethinyloestradiol
      and levonorgestrel.

PMID- 18333863
TI  - Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy
      volunteers.
AB  - AIMS: To evaluate the influence of cytochrome P450 (CYP) 3A4 inhibitors on the
      clinical pharmacokinetics of maraviroc, a novel CCR5 antagonist. METHODS: Four
      open-label, randomized, placebo-controlled studies were conducted in healthy
      subjects to assess the effect of separate and distinct combinations of CYP3A4
      inhibitors on the steady-state pharmacokinetics of maraviroc. Study 1 was a two
      way crossover study investigating the influence of saquinavir (SQV; 1200 mg
      t.i.d.) and ketoconazole (400 mg q.d.) on the pharmacokinetics of maraviroc (100
      mg b.i.d.). All subjects received maraviroc for 7 days in both study periods.
      Cohort 1 subjects also received SQV or placebo and cohort 2 subjects also
      received ketoconazole or placebo. Study 2 was a parallel-group study including
      four treatment groups investigating the effects of ritonavir-boosted lopinavir
      (LPV/r; 400 mg/100 mg b.i.d.), ritonavir-boosted saquinavir (SQV/r; 1000 mg/100
      mg b.i.d.), and low-dose ritonavir (RTV; 100 mg b.i.d.) on the steady-state
      pharmacokinetics of maraviroc (100 mg b.i.d.), and exploring whether maraviroc
      dose adjustment can compensate for interaction effects. Treatment lasted 28 days
      and comprised three distinct phases: (i) maraviroc alone on days 1-7; (ii)
      maraviroc + interactant on days 8-21; and (iii) maraviroc (adjusted dose) +
      interactant on days 22-28. Study 3 was a two-way crossover study investigating
      the effects of atazanavir (ATZ; 400 mg q.d.) and ritonavir-boosted atazanavir
      (ATZ/r; 300 mg/100 mg b.i.d.) on the pharmacokinetics of maraviroc (300 mg
      b.i.d.). All subjects received maraviroc on days 1-14 of both study periods.
      Subjects also received ATZ on days 1-7 and ATZ/r on days 8-14 of one treatment
      period, and placebo on days 1-14 of the other treatment period. Study 4 was a two
      way crossover study investigating the effects of ritonavir-boosted tipranavir
      (TPV/r; 500 mg/200 mg b.i.d.) on the pharmacokinetics of maraviroc (150 mg
      b.i.d.). Subjects received maraviroc plus TPV/r or placebo on days 1-8. RESULTS:
      All of the drugs/drug combinations tested (except for TPV/r) increased maraviroc
      exposure, albeit to different degrees of magnitude. SQV/r caused the largest
      increase in maraviroc exposure (8.3-fold increase in AUC(tau)), whereas RTV
      caused the smallest increase in maraviroc exposure (2.6-fold increase in
      AUC(tau)). Downward adjustment of the maraviroc dose in study 2 during co
      administration of HIV protease inhibitors was able to compensate for the
      interactions. TPV/r had no clinically relevant effect on maraviroc exposure at
      steady state. There were no treatment-related serious adverse events or
      discontinuations due to adverse events in any of the studies, and most adverse
      events were mild or moderate in severity and resolved without intervention.
      CONCLUSIONS: Potent CYP3A4 inhibitors, including ketoconazole and protease
      inhibitors (except TPV/r), increase maraviroc exposure. Downward adjustment of
      the maraviroc dose during co-administration with protease inhibitors can
      compensate for the interaction. TPV/r does not affect the steady-state
      pharmacokinetics of maraviroc, and hence no dose adjustment would be warranted.

PMID- 18333864
TI  - Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the
      pharmacokinetics of maraviroc in healthy volunteers.
AB  - AIMS: To assess the potential of known CYP3A4 inducers, with and without CYP3A4
      inhibitors, to alter the pharmacokinetic profile of maraviroc. METHODS: Two
      separate, open, randomized, placebo-controlled studies were conducted in healthy
      subjects. Study 1 was a 28-day parallel-group study with three treatment groups
      of 12 subjects each. On days 1-7, all subjects received maraviroc 100 mg b.i.d.;
      on days 8-21, subjects received maraviroc 100 mg b.i.d. plus either rifampicin
      600 mg q.d., efavirenz (EFV) 600 mg q.d., or placebo q.d. as assigned; on days 22
      28, the maraviroc dose was increased to 200 mg b.i.d. for patients receiving
      either rifampicin or EFV. Study 2 was a 21-day, two-way crossover study with
      three cohorts (12 subjects per cohort). On days 1-21, subjects received maraviroc
      300 mg b.i.d. and boosted lopinavir (LPV/r, lopinavir 400 mg + ritonavir 100 mg)
      or placebo b.i.d. in cohort 1, maraviroc 100 mg b.i.d. and boosted saquinavir
      (SQV/r, saquinavir 1000 mg + ritonavir 100 mg) or placebo b.i.d. in cohort 2, and
      maraviroc 100 mg b.i.d. and 1000 mg saquinavir + LPV/r (400 mg/100 mg) or placebo
      b.i.d. in cohort 3. On days 8-21, subjects in all three cohorts also received EFV
      600 mg or placebo q.d. RESULTS: Maraviroc (100 mg b.i.d.) exposure (AUC(12) and
      C(max)) was reduced in the presence of rifampicin and EFV by approximately 70%
      and 50%, respectively. Maraviroc AUC(12) and C(max) approached preinduction
      values when the maraviroc dose was increased to 200 mg b.i.d. for both the
      rifampicin-treated and EFV-treated groups. Co-administration of LPV/r with
      maraviroc (300 mg b.i.d.) resulted in geometric mean ratios (GMRs) of 395% and
      197% for maraviroc AUC(12) and C(max), respectively, compared with placebo;
      addition of EFV resulted in GMRs of 253% and 125% for AUC(12) and C(max),
      respectively. Co-administration of SQV/r with maraviroc (100 mg b.i.d.) resulted
      in GMRs of 977% and 478% for maraviroc AUC(12) and C(max), respectively, compared
      with placebo; addition of EFV resulted in GMRs of 500% and 226% for AUC(12) and
      C(max), respectively. No pharmacokinetic data are reported for cohort 3 because
      all subjects were discontinued during period 1 due to poor toleration of the drug
      regimen. There were no serious adverse events reported in either study, and most
      adverse events were mild or moderate in severity and resolved without
      intervention. CONCLUSION: As expected with a CYP3A4 substrate, maraviroc exposure
      (C(max) and AUC(12)) was significantly reduced by the known CYP3A4 inducers,
      rifampicin and EFV, by approximately 70% and 50%, respectively. Upward adjustment
      of the maraviroc dose during co-administration with rifampicin or EFV appears to
      compensate for this reduction. Protease inhibitors (PIs) significantly increased
      maraviroc exposure; however, the addition of EFV to the maraviroc + PI regimens
      reduced the magnitude of PI-mediated increase in maraviroc exposure (by
      approximately 50%), but the net effect was still CYP3A4 inhibition.

PMID- 18333865
TI  - The effects of cotrimoxazole or tenofovir co-administration on the
      pharmacokinetics of maraviroc in healthy volunteers.
AB  - AIMS: To assess the potential of cotrimoxazole and tenofovir, drugs which are
      inhibitors and/or substrates of renal transporters, to alter the pharmacokinetic
      profile of maraviroc. METHODS: Two randomized, placebo-controlled, two-way
      crossover studies were conducted in healthy male and female subjects. In study 1,
      16 subjects, aged 18-45 years, received maraviroc (300 mg b.i.d.) with and
      without cotrimoxazole (960 mg b.i.d.; 160 mg trimethoprim and 800 mg
      sulfamethoxazole). In study 2, 12 subjects, aged 21-45 years, received maraviroc
      (300 mg b.i.d.) with and without tenofovir (300 mg q.d.). For study 1, blood was
      collected predose and on days 1-7. In study 2, blood was collected predose, on
      day 1 and days 3-7. In both studies, blood was collected at intervals up to 12 h
      postdose on day 7. Urine was collected on day 7, 0-12 h post morning dose. Blood
      and urine were analysed for maraviroc using liquid chromatography/tandem mass
      spectrometry. RESULTS: The geometric mean ratios for C(max) and AUC(12) were 119%
      and 111%, respectively, for maraviroc plus cotrimoxazole and 104% and 103%,
      respectively, for maraviroc plus tenofovir, compared with maraviroc plus placebo.
      Renal clearance of maraviroc plus placebo was 8.3 l h(-1) and 8.5 l h(-1) and was
      7.8 l h(-1) for maraviroc plus cotrimoxazole and maraviroc plus tenofovir. There
      were no serious or severe adverse events or any clinically significant changes in
      laboratory tests, blood pressure, or electrocardiograms. CONCLUSIONS: Neither
      cotrimoxazole nor tenofovir caused a clinically significant effect on the
      pharmacokinetics of maraviroc. Maraviroc 300 mg b.i.d. was well tolerated when co
      administered with either cotrimoxazole or tenofovir.

PMID- 18333866
TI  - A novel probe drug interaction study to investigate the effect of selected
      antiretroviral combinations on the pharmacokinetics of a single oral dose of
      maraviroc in HIV-positive subjects.
AB  - AIMS: Maraviroc (UK-427 857), an antagonist of the CCR5 receptor with potent anti
      HIV activity, was recently approved for use in treatment-experienced patients
      infected with CCR5-tropic HIV-1. The aim of this study was to evaluate the effect
      of selected commonly used antiretroviral therapy (ART) combinations on the
      pharmacokinetics of a single oral dose of maraviroc 300 mg in HIV-positive
      subjects compared with historical controls. METHODS: In this study, four cohorts
      of HIV-positive patients (n = 8 each) receiving one of the following combination
      therapies were recruited: cohort 1--efavirenz + Combivir (lamivudine/zidovudine);
      cohort 2--efavirenz + didanosine + tenofovir; cohort 3--nevirapine + lamivudine +
      tenofovir; cohort 4--Kaletra (lopinavir/ritonavir) + stavudine + lamivudine.
      Subjects continued on their prescribed ART and also received a single oral dose
      of maraviroc 300 mg. Serial blood samples and urine for determination of
      maraviroc pharmacokinetics were collected over 12 h postdose. Plasma
      pharmacokinetic parameters from this study were compared with historical data
      generated in HIV-positive subjects receiving maraviroc monotherapy in a Phase IIa
      study. RESULTS: A total of 29 subjects were recruited (eight each in cohorts 1-3,
      and five in cohort 4). The geometric mean ratios for AUC(12) and C(max) for each
      treatment group compared with maraviroc monotherapy were: 47% and 67% (cohort 1);
      48% and 76% (cohort 2); 101% and 154% (cohort 3); and 265% and 180% (cohort 4),
      respectively. T(max) was similar in all treatment groups. Mean values for renal
      clearance ranged from 8.2 l h(-1) (cohort 1) to 13.2 l h(-1) (cohort 4). There
      were no renal clearance data collected in the comparator study. CONCLUSIONS: The
      results of this study support those previously seen in healthy volunteer studies
      that showed that efavirenz reduces maraviroc exposure, whereas
      lopinavir/ritonavir increases maraviroc exposure. These data also suggest that
      nevirapine does not lead to a clinically significant effect on maraviroc
      pharmacokinetics.

PMID- 18333867
TI  - Assessment of the absorption, metabolism and absolute bioavailability of
      maraviroc in healthy male subjects.
AB  - AIMS: Two studies were conducted to: (i) quantify the amount of drug-related
      radioactivity in blood, plasma, urine and faeces following a (14)C-labelled dose
      of maraviroc; and (ii) investigate the pharmacokinetics, safety and tolerability
      of intravenous (i.v.) maraviroc and determine the absolute bioavailability of
      oral maraviroc. Metabolite profiling was also conducted. Data from both of these
      studies were used to construct a mass-balance model for maraviroc. METHODS: Study
      1 was an open-label study in three healthy male subjects. All subjects received a
      single 300-mg oral solution dose of (14)C-labelled maraviroc. Study 2 included
      two cohorts of subjects. Cohort 1 involved a double-blind (third party open),
      four-way crossover study where eight subjects received escalating i.v. doses of
      maraviroc (3, 10 and 30 mg) with placebo insertion. Cohort 2 involved an open,
      two-way crossover study where 12 subjects received 30 mg maraviroc by i.v.
      infusion and 100 mg maraviroc orally in random order. In study 1, blood samples
      and all urine and faeces were collected up to at least 120 h postdose. In study
      2, blood samples were taken at intervals up to 48 h postdose. Urine was also
      collected up to 24 h postdose in cohort 1 only. RESULTS: After oral
      administration in study 1, maraviroc was rapidly absorbed with a plasma T(max)
      reached by 2 h postdose for all three subjects. The maximum concentrations of
      radioactivity also occurred within 2 h for all subjects. There was a higher
      amount of radioactivity in plasma than in blood (blood/plasma ratio approximately
      0.6 for AUC(t) and C(max)). Unchanged maraviroc was the major circulating
      component in plasma, accounting for approximately 42% of the circulating
      radioactivity. Following a 300-mg (14)C-labelled maraviroc dose, means of 76.4%
      and 19.6% of radioactivity were recovered in the faeces and urine, respectively.
      The mean total recovery of dosed radioactivity was 96%, with the majority of
      radioactivity being recovered within 96 h postdose. Profiling of the urine and
      faeces showed similar and extensive metabolism in all subjects. Unchanged
      maraviroc was the major excreted component (33%). The major metabolic pathways
      were determined and involved oxidation and N-dealkylation. Intravenous doses of
      maraviroc (3-30 mg) were well tolerated in study 2, and drug exposure was
      approximately proportional to dose within the studied range. Approximately 23% of
      total clearance (44 l h(-1)) was accounted for by renal clearance (10.2 l h(-1)).
      Mean volume of distribution at steady state was 194 l. Absolute bioavailability
      of a 100-mg oral tablet dose, by comparison with a 30-mg i.v. dose, was
      calculated to be 23.1%. CONCLUSIONS: Maraviroc is rapidly absorbed and
      extensively metabolized, although unchanged maraviroc is the major circulating
      component in plasma and is the major excreted component after oral dosing. The
      pharmacokinetics of maraviroc after i.v. administration is approximately
      proportional over the dose range studied. Renal clearance contributes 23% of
      total clearance. The absolute bioavailability of 100 mg oral maraviroc is 23%.

PMID- 18333868
TI  - Effect of single doses of maraviroc on the QT/QTc interval in healthy subjects.
AB  - AIMS: To assess the effect of a single dose of maraviroc on the QTc interval in
      healthy subjects and to evaluate the QTc interval-concentration relationship.
      METHODS: A single-dose, placebo- and active-controlled, five-way crossover study
      was conducted to investigate the effects of maraviroc (100, 300, 900 mg) on QTc
      in healthy subjects. Moxifloxacin (400 mg) was used as the active comparator. The
      study was double-blind with respect to maraviroc/placebo and open label for
      moxifloxacin. There was a 7-day wash-out period between each dose. QT interval
      measurements obtained directly from the electrocardiogram (ECG) recorder were
      corrected for heart rate using Fridericia's correction (QTcF). A placebo run-in
      day was conducted before period 3, when ECGs were collected at intervals while
      subjects were resting or during exercise. These ECGs plus other predose ECGs were
      used to evaluate the QT/RR relationship for each subject to enable calculation of
      an individual's heart rate correction for their QT measurements (QTcI). ECGs were
      taken at various intervals pre- and postdose in each study period.
      Pharmacokinetic parameters were determined for each maraviroc dose. The end
      points that were evaluated were QTcF at median time to maximum concentration
      (T(max)) based on the machine readings and QTcI at median T(max) based on manual
      over-reads of the QT/RR data. A separate analysis of variance was used for each
      of the pair-wise comparisons for each end-point. The relationship between QTc
      interval and plasma concentration was also investigated using a mixed-effects
      modelling approach, as implemented by the NONMEM software system. A one-stage
      model was employed in which the relationship between QT and RR and the effects of
      maraviroc plasma concentration on QT were estimated simultaneously. RESULTS: The
      mean difference from placebo in machine-read QTcF at median T(max) for maraviroc
      900 mg was 3.6 ms [90% confidence interval (CI) 1.5, 5.8]. For the active
      comparator, moxifloxacin, the mean difference from placebo in machine-read QTcF
      was 13.7 ms. The changes from placebo for each of the end-points were similar for
      men and women. No subjects receiving maraviroc or placebo had a QTcF > or = 450
      ms (men) or QTcF > or = 470 ms (women), nor did any subject experience a QTcF
      increase > or = 60 ms from baseline at any time point. Analysis based on the QTcI
      data obtained from the manual over-readings of the ECGs gave numerically very
      similar results. The QT:RR relationship was similar pre- and postdose and was not
      related to maraviroc concentration. The population estimate of the QT:RR
      correction factor was 0.324 (95% CI 0.309, 0.338). The population estimate of the
      slope describing the QT-concentration relationship was 0.97 micros ml ng(-1) (95%
      CI -0.571, 2.48), equivalent to an increase of 0.97 ms in QT per 1000 ng
      maraviroc plasma concentration. Most adverse events were mild to moderate in
      severity. CONCLUSIONS: Single doses of maraviroc, up to and including 900 mg, had
      no clinically relevant effect on QTcF or QTcI. At all maraviroc doses and for
      both end-points, the mean difference from placebo for QTc was < 4 ms. There was
      no apparent relationship between QT interval and maraviroc plasma concentration
      up to 2363 ng ml(-1). This conclusion held in both male and female subjects, and
      there was no evidence of a change in the QT/RR relationship with concentration.

PMID- 18333869
TI  - A population pharmacokinetic meta-analysis of maraviroc in healthy volunteers and
      asymptomatic HIV-infected subjects.
AB  - AIMS: To develop a population pharmacokinetic model for maraviroc, a
      noncompetitive CCR5 antagonist, after oral administration of tablets to healthy
      volunteers and asymptomatic HIV-infected subjects and to quantify the inherent
      variability and influence of covariates on the parameters of the model. METHODS:
      Rich pharmacokinetic data available from 15 studies in healthy volunteers (n =
      365) and two studies in asymptomatic HIV-infected subjects (n = 48) were analysed
      using NONMEM. Maraviroc was administered as single or multiple oral tablet doses
      under fasted and fed conditions. Doses ranged from 100 to 1800 mg day(-1).
      RESULTS: A two-compartment model parameterized to separate out absorption and
      clearance components on bioavailability was used. Absorption was described by a
      lagged first-order process. A sigmoid E(max) model described the effect of dose
      on absorption. A visual predictive check and nonparametric bootstrap evaluation
      confirmed that the model was a good description of the data. Typical CL, V(c) and
      V(p) values for a 30-year-old non-Asian are 51.5 l h(-1), 132 l and 277 l,
      respectively. CONCLUSIONS: For the typical non-Asian subject, fasted
      bioavailability increased asymptotically with dose from 24% at 100 mg to 33% at
      600 mg. A high-fat meal taken with maraviroc reduced exposure by 43% for a 100-mg
      dose to approximately 25% at doses of 600 mg. The typical Asian subject had a
      26.5% higher AUC than the typical non-Asian subject irrespective of dose, a
      difference not considered to be clinically relevant. None of the other covariates
      tested had any clinically relevant effects on exposure.

PMID- 18333870
TI  - Population pharmacokinetic/pharmacodynamic analysis of CCR5 receptor occupancy by
      maraviroc in healthy subjects and HIV-positive patients.
AB  - BACKGROUND: Maraviroc, a noncompetitive antagonist of the CCR5 coreceptor, was
      recently approved in the USA as a treatment of HIV infection. For antiretroviral
      agents that target the virus, antiviral effect can be related to some extent to
      plasma drug concentrations. For CCR5 antagonists that target the host cells,
      receptor occupancy in vivo might be a better predictor of efficacy. AIMS To
      develop a population pharmacokinetic (PK)-pharmacodynamic (PD) model that
      describes CCR5 receptor occupancy by maraviroc after oral administration at
      different doses in healthy volunteers and HIV-positive patients and to assess the
      relevance of receptor occupancy in predicting the decrease in viral load (HIV-1
      RNA copies ml(-1)) in HIV-positive patients. METHODS: Receptor occupancy data
      from 88 individuals enrolled in two multiple dose trials were included in the
      population PK-receptor binding model. Out of the 88 individuals, 25 were HIV-1
      infected patients and had viral load measurements, whereas the remaining 63 were
      healthy volunteers. Doses ranged from 3 mg b.i.d. to 600 mg q.d. A previously
      published PK-PD disease model describing the effect of maraviroc on the viral
      load was updated by replacing its PD module by the receptor occupancy model.
      Simulated viral load-time profiles with the updated model were compared with the
      profiles observed in patients. RESULTS: The majority of measured plasma
      concentrations were associated with receptor occupancy > or = 50% even at the
      lowest dose of 3 mg b.i.d. A simple direct E(max) model appeared to describe
      satisfactorily the PK-receptor occupancy relationship. The estimated K(D) was
      around 0.0894 ng ml(-1), far below the operational in vivo antiviral IC(50) of 8
      ng ml(-1). Accordingly, simulations led to marked overprediction of the decrease
      in viral load-time profiles. CONCLUSIONS: Maraviroc receptor occupancy close to
      the maximum is required to induce a significant decrease in viral load,
      indicating that in vivo CCR5 receptor occupancy by maraviroc is not a direct
      measure of drug inhibitory activity. Considering the imprecision of the
      measurement in the upper flat part of the maraviroc concentration vs. percent
      CCR5 occupancy curve, it can reasonably be concluded that routine monitoring of
      receptor occupancy as a biomarker for maraviroc efficacy will not be helpful.
      Based on this analysis, it was decided not to use receptor occupancy as a
      biomarker of viral load inhibition during the development of CCR5 antagonist
      compounds.

PMID- 18333871
TI  - A receptor theory-based semimechanistic PD model for the CCR5 noncompetitive
      antagonist maraviroc.
AB  - AIM: To develop a novel combined viral dynamics/operational model of (ant
      )agonism that describes the pharmacodynamic effects of maraviroc, a
      noncompetitive CCR5 inhibitor, on viral load. METHODS: A common theoretical
      framework based on receptor theory and the operational model of (ant-)agonism has
      been developed to describe the binding of maraviroc to the CCR5 receptor and the
      subsequent decrease in viral load. The anchor point of the operational model in
      the differential equations of the viral dynamic model is the infection rate
      constant; this is assumed to be dependent on the number of free activated
      receptors on each target cell. RESULTS: The new model provides one explanation
      for the apparent discrepancy between the in vivo binding of maraviroc to the CCR5
      receptor (K(D) = 0.089 ng ml(-1)) and the estimated in vivo inhibition (IC(50) =
      8 ng ml(-1)) of the infection rate. The estimated K(E) value of the operational
      model indicates that only 1.2% of free activated receptors are utilized to elicit
      50% of the maximum infection rate. CONCLUSIONS: The developed model suggests that
      the target cells, when activated, express more receptors (spare receptors) than
      needed. In the presence of maraviroc these spare receptors first require blocking
      before any decrease in the infection rate, and consequently in the viral load at
      equilibrium, can be detected. The model allows the simultaneous simulation of the
      binding of maraviroc to the CCR5 receptor and the change in viral load after both
      short- and long-term treatment.

PMID- 18333872
TI  - European citizens' opinions on water fluoridation.
AB  - OBJECTIVES: To understand European citizens' opinions on water fluoridation, as
      part of research on their attitudes to the tensions between private and public
      interest. METHODS: Sixty-eight focus groups held (with an average of eight people
      per group) in September and October 2003 in 16 countries (Austria, Belgium,
      Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, the
      Netherlands, Poland, Portugal, Spain, Sweden and the UK). RESULTS: Most
      participants were against water fluoridation, although groups in Greece, Ireland,
      Poland and Sweden were more in favour. Many felt dental health was an issue to be
      dealt with at the level of the individual, rather than a solution to be imposed
      en masse. While people accepted that some children were not encouraged to brush
      their teeth, they proposed other solutions to addressing these needs rather than
      having a solution of unproved safety imposed on them by public health authorities
      whom they did not fully trust. They did not see why they should accept potential
      side effects in order that a minority may benefit. In particular, water was
      something that should be kept as pure as possible, even though it was recognized
      that it already contains many additives. CONCLUSIONS: While the vast majority of
      people opposed water fluoridation, this may be indicative of shifts away from
      public support of population interventions towards private interventions, as well
      as reduced trust in public agencies. Thus if research were to demonstrate more
      clear benefits of water fluoridation over and above that which can be achieved by
      use of fluoride toothpaste, then the public may become more supportive. However,
      lobby groups are likely to remain influential.

PMID- 18333873
TI  - Water fluoridation as a marker for sociodental inequalities.
AB  - OBJECTIVES: The aim of this study was to investigate the associations between the
      Human Development Index at city level (HDI-M) in the state of Parana, Brazil, and
      the length of time of population exposure to water fluoridation (time span) with
      the respective mean decayed, missing and filled teeth (DMF-T) of schoolchildren
      in the state, looking at possible inequalities in these associations. METHODS:
      The HDI-M of 323 cities in the state of Parana, Brazil, was correlated to the
      duration of exposure to water fluoridation, calculated in number of days.
      Correlation between the HDI-M and the DMF-T indexes for 12-year-old children was
      also performed. RESULTS: Correlations were statistically significant, showing
      that in the cities with a better HDI-M, water fluoridation had been implemented
      earlier (squared coefficient correlation of 22%). The fluoridation time span
      accounted for around 11% of the variance in the DMF-T indexes of the cities. The
      correlation indicated that locations with a better HDI-M had a better DMF-T,
      owing to the probable mediating effect of receiving fluoridation earlier.
      Furthermore, the cost of water fluoridation to benefit the population that has
      access to this public health measure has been estimated at USD 0.15 per
      capita/year. CONCLUSIONS: It is possible to conclude that this low-cost measure
      is able to improve oral health status in general. Nevertheless, in the Brazilian
      areas studied, fluoridation seems to reflect existing social development
      inequalities, as it was first made available in more socially developed areas,
      thus bearing an influence on their higher DMF-T performance to date.

PMID- 18333874
TI  - Changes in parent-assessed oral health-related quality of life among young
      children following dental treatment under general anaesthetic.
AB  - OBJECTIVE: To estimate the nature and magnitude of changes in oral health-related
      quality of life (OHRQoL) among children having dental treatment under general
      anaesthetic (GA) and to examine the evaluative properties of the Child Oral
      Health-related Quality of Life Questionnaire (COHQOL). METHODS: Data from a
      consecutive clinical sample of the parents/caregivers of children receiving
      dental treatment under GA at Wellington and Kenepuru Hospitals were collected
      from parents using the Parental-Caregivers Perception Questionnaire (P-CPQ) and
      the Family Impact Scale (FIS), which both form part of the COHQOL Questionnaire.
      The first questionnaire was completed before treatment or while the participant's
      child was undergoing treatment. The follow-up questionnaire was completed 1-4
      weeks afterward. Treatment-associated changes in OHRQoL were determined by
      comparing baseline and follow-up data for the mean scores and the prevalence of
      impacts. The discriminative properties of the instrument were confirmed and then
      its evaluative properties were assessed (by examining its test-retest
      reliability, responsiveness and longitudinal construct validity). The minimally
      important difference was determined for the overall scale and subscales. RESULTS:
      Complete baseline and follow-up data were obtained for 202 and 130 participants,
      respectively (64.4% follow-up rate). The evaluative properties of the P-CPQ and
      FIS were acceptable. There were substantial and highly statistically significant
      reductions in mean P-CPQ and FIS scores after treatment, with effect sizes
      ranging from moderate to large, depending on the subscale being examined. The
      minimally important difference was shown by almost two-thirds of the children
      treated. CONCLUSION: The provision of dental treatment under GA for young
      children with severe dental caries experience is associated with substantial and
      highly significant improvements in both their OHRQoL and in the impact on their
      families. The P-CPQ and the FIS show promise as evaluative measures for use in
      dental health services research.

PMID- 18333875
TI  - Changes in dental status and dental care utilization in the Swedish population
      over three decades: age, period, or cohort effects?
AB  - OBJECTIVES: In cross-sectional data, cohort effects give a false impression of
      changes in edentulousness over age and time. This study, therefore, corroborated
      cross-sectional data with corresponding longitudinal analyses. Complete or
      partial edentulousness and yearly dental care utilization were studied from 1968
      to 2002. METHODS: A nationally representative Swedish panel study allowed
      repeated cross-sectional comparisons of ages 18-75 (5 waves n approximately
      5000), and ages 77+ at later waves (2 waves n approximately 500). Cross-sectional
      10-year age group differences in 5 waves, time-lag differences between waves for
      age groups, and within-cohort differences between waves for 10-year birth cohorts
      were examined. RESULTS: Regular over time analysis revealed large decreases in
      edentulousness between waves. While cross-sectional differences indicated an
      exponential curve-linear age-dependency, longitudinal differences revealed little
      decline, contradicting cross-sectional results. Following the cohorts showed
      little change within cohorts but large differences between cohorts. Care
      utilization increased between 1968 and 2002 in older age groups but decreased
      somewhat in younger ones. In 1968, utilization was highly age-related with lower
      utilization rates among older age groups. By 2000/2002, this had almost reversed.
      However, all cohorts had aged with little change in their rates of care
      utilization, while at the same time great between-cohort differences were
      demonstrated. CONCLUSIONS: For both edentulousness and dental care utilization,
      almost all variation originated before 1968. These cohort effects are probably
      the consequences of changes in dentistry going back several decades and they
      demonstrate the early socialization of health behavior.

PMID- 18333876
TI  - A preliminary investigation of the relationship of dental fear to other specific
      fears, general fearfulness, disgust sensitivity and harm sensitivity.
AB  - OBJECTIVES: People with dental fear often suffer from other psychological
      disorders, as well as from a number of other specific fears. Fear of going to the
      dentist may be associated not only with general fearfulness, but also with
      underlying personality dispositions. This exploratory study, therefore,
      investigated the associations between dental fear and 67 other specific fears,
      general fearfulness, disgust sensitivity and harm sensitivity. METHODS:
      Participants were 88 Australian adults who were administered the Fear Survey
      Schedule III (FSS-III), the Harm Sensitivity Index and the Disgust Sensitivity
      Index. Principle axis factor analysis with Promax rotation was used to examine
      how dental fear related to other specific fears as measured with the FSS-III.
      RESULTS: Dental fear was significantly correlated with most of the other specific
      fears, with factor analysis indicating that it tended to load more with fears
      related to lack of control rather than with what have often been classed as
      'medical' fears. Significant associations were found between dental fear and the
      personality dispositions of general fearfulness, harm sensitivity and disgust
      sensitivity, although these associations were not linear. CONCLUSIONS: Findings
      reveal extensive co-occurrence of other specific fears with dental fear, while
      the associations of dental fear with personality traits suggest enduring aspects
      to dental fear which may translate into difficulties in fear alleviation. Dental
      fear was more related to a diverse range of fears relating to a loss of control
      than to medical-specific fears.

PMID- 18333877
TI  - Does malocclusion influence the adolescent's satisfaction with appearance? A
      cross-sectional study nested in a Brazilian birth cohort.
AB  - OBJECTIVES: To test whether malocclusion had an impact on adolescents' appearance
      satisfaction regardless of other physical aspects. METHODS: A cross-sectional
      study nested in a birth cohort study was carried out in Pelotas, Brazil. A random
      sample of 900 15-year-old adolescents was selected. WHO criteria were used to
      define malocclusion and a questionnaire was administered including self-reported
      skin colour and appearance satisfaction. Dental caries were assessed. Height and
      weight were measured and body mass index calculated. Data concerning gender and
      socioeconomic characteristics were obtained from the cohort's perinatal study.
      Adjusted analyses including all confounding variables investigated were performed
      using Poisson regression with robust variance in order to identify the potential
      risk factors for appearance dissatisfaction. All analyses were carried out
      separately by gender. RESULTS: The sample included 867 individuals, 54.1% men.
      The prevalence of moderate or severe malocclusion was 30.6% (95% CI: 26.5-34.7)
      among boys, and 32.8% (95% CI: 28.2-37.4) among girls (P = 0.524).
      Dissatisfaction with appearance was reported by 29.8% of the boys and by 46.5% of
      the girls (P < 0.001). A positive association between malocclusion and appearance
      dissatisfaction, controlling for other physical, dental caries and socioeconomic
      characteristics was observed only in girls [prevalence ratio = 1.4 (1.3-1.7)].
      CONCLUSIONS: Malocclusion is a common condition and is positively associated with
      appearance dissatisfaction in adolescent girls. The effect of different types of
      malocclusion on appearance dissatisfaction should be the focus of further
      investigation.

PMID- 18333878
TI  - Risk factors associated with dental fluorosis in Central Plateau State, Nigeria.
AB  - OBJECTIVES: Dental fluorosis is known to occur in some parts of Plateau State,
      but the factors responsible for its occurrence are unknown. The purpose of this
      study, therefore, was to determine the factors associated with the occurrence of
      dental fluorosis in Central Plateau. METHODS: The study was cross-sectional and
      comparative in design. Subjects were selected using the multi-stage sampling
      technique. One Local Government Area each was randomly selected from the high and
      low altitude parts of the district, and from each selected Local Government Area
      two health districts were randomly selected with probability proportional to
      size. From each of the selected health districts two major settlements were
      selected again with probability proportional to size. Twelve- to fifteen-year-old
      lifelong residents of the selected settlements were then selected for study. Each
      respondent completed an interviewer-administered questionnaire after which he/she
      was clinically examined to ascertain his/her fluorosis status. Samples of water
      were collected from water sources consumed by the respondents in each settlement.
      RESULTS: One thousand one hundred children aged 12-15 years were studied, 554
      (50.4%) of which lived in the high altitude part of the district and 546 (49.6%)
      in the low altitude part of the district. Fluorosis prevalence was significantly
      associated with altitude and the fluoride level of water. The prevalence of
      fluorosis was significantly associated with altitude (chi(2) = 85.735, d.f. = 1,
      P < 0.0001) and the fluoride level of water (chi(2) for trend = 8.009, d.f. = 1,
      P < 0.05) in the low altitude parts of the district. None of the respondents had
      used fluoride-containing toothpaste before 4 years of age and none used fluoride
      supplements. CONCLUSION: The occurrence of dental fluorosis in Central Plateau
      could be because of the high altitude of the area and the fluoride concentration
      of the waters consumed in the district.

PMID- 18333879
TI  - Contributions of social context to inequality in dental caries: a multilevel
      analysis of Japanese 3-year-old children.
AB  - BACKGROUND: Community context as well as individual health behavior affects oral
      health status. However, the contribution of social context to dental caries among
      people in various regions remains unclear when individual health behavior is
      taken into account. OBJECTIVES: To determine the influence of community context
      on dmft among 3-year-old children. METHODS: After all Japanese municipalities (n
      = 2522) had been stratified into nine regions with three caries levels, 44
      municipalities were randomly selected. Community health service workers were
      asked to collect information on sociodemographic characteristics, oral health
      related behavior, and dental condition for 3-year-old children during community
      dental health check-ups. Community-related variables, including socioeconomic
      status, social support, and social cohesion, were obtained from census data.
      Multilevel analysis was used to determine the effects of social context and
      individual behavior on dental caries. RESULTS: A total of 3301 parents (79.9%) of
      3-year-old children from 39 municipalities participated in our survey, and
      complete information was obtained from 3086 of them. Results of the analysis
      showed that 90.8% (P < 0.001) of variance in dmft occurred at the individual
      level and that 9.2% (P < 0.001) of the variance occurred at the community level.
      Individual-level variables explained only 6.6% of the individual level variance
      in dmft. Community-level variables explained 47.2% of the community level
      variance. CONCLUSIONS: There are statistically significant effects of social
      context on dmft in municipalities in Japan.

PMID- 18333880
TI  - Caries status and overweight in 2- to 18-year-old US children: findings from
      national surveys.
AB  - BACKGROUND: The prevalence of overweight children in the United States continues
      to increase. OBJECTIVES: To examine the relationship between being overweight and
      caries in primary and permanent dentition in a nationally representative sample
      of children. METHODS: Data from the NHANES III (1988-1994) were analyzed using
      logistic regression and controlling for potential confounders for 10 180 children
      2-18 years of age and from the NHANES 1999-2002 for 7568 children 2-18 years of
      age. RESULTS: For children 2-5 years of age, there was no difference in caries
      experience among normal weight, at risk for overweight or overweight children for
      NHANES III and for NHANES 1999-2002. For children 6-11 years of age (NHANES III),
      at risk for overweight and overweight children were less likely to have caries
      experience in the primary dentition than normal weight children; overweight
      children were less likely to have caries experience in the permanent dentition
      than normal weight children. For children 12-18 years of age (NHANES III),
      overweight children were less likely to have caries experience in the permanent
      dentition than normal weight children. For children 6-11 years of age and 12-18
      years of age (NHANES 1999-2002), there was no difference in having caries
      experience among normal, at risk for overweight and overweight children.
      CONCLUSIONS: The data from NHANES III and NHANES 1999-2002 provide no evidence to
      suggest that overweight children are at an increased risk for dental caries.
      Although no differences in caries rates by weight were found in younger children,
      interestingly results from NHANES III suggest that being overweight may be
      associated with decreased rates of caries in older children.

PMID- 18333881
TI  - Factors associated with prevalence and severity of caries experience in preschool
      children.
AB  - OBJECTIVES: The aim of the present study was to examine the prevalence and
      severity of caries experience in the primary dentition of preschool children and
      to assess the association of disease distribution with oral hygiene levels,
      reported oral health behaviours and socio-demographic factors. METHODS: Study
      samples comprised 1250 3-year-old and 1283 5-year-old pre-school children from
      four distinct geographical areas in Flanders. Information on oral hygiene and
      dietary habits, oral health behaviours and socio-demographic variables was
      collected using questionnaires completed by the parents. Clinical examinations
      were performed using standardized criteria. Caries experience was recorded at the
      level of cavitation (d(3) level). Simple as well as multivariable logistic
      regression analyses were performed in order to identify factors associated with
      prevalence and severity of caries experience. RESULTS: Visible plaque was present
      in 31% of 3-year-olds and 37% of 5-year-olds. In 3-year-olds, 7% presented with
      caries experience while this was the case in 31% of 5-year-olds. Multivariable
      logistic regression revealed significant associations, in 3-year-olds, of caries
      experience with presence of dental plaque (OR = 7.93; 95% CI: 2.56-24.55) and
      reported consumption of sugared drinks at night (OR = 7.96; 95% CI: 1.57-40.51).
      In 5-year-olds, significant associations were seen with age (OR = 7.79; 95% CI:
      2.38-25.43), gender (OR = 0.37 with 95% CI: 0.19-0.71 for girls), presence of
      visible dental plaque (OR = 3.36; 95% CI: 1.64-6.89) and reported habit of having
      sugar-containing drinks in between meals (OR = 2.60 with 95% CI: 1.16-5.84 and OR
      = 3.18 with 95% CI: 1.39-7.28, respectively for 1x/day and > 1x/day versus not
      every day). In 5-year-olds with caries experience (30.8% of total sample), the
      severity of disease was further analysed (d(3)mft between 1 and 4 versus d(3)mft
      5 or higher). Multivariable analyses showed a significant association with gender
      [girls more likely to have higher disease levels; OR = 4.67 (95% CI: 1.65-13.21)]
      and with presence of plaque (OR = 3.91 with 95% CI: 1.23-12.42). CONCLUSIONS:
      Presence of visible plaque accumulation and reported consumption of sugared
      drinks were associated with prevalence of caries experience in Flemish preschool
      children. Severity of disease was associated with gender and with presence of
      plaque. Results underline the importance of plaque control and diet management
      from very young age on.

PMID- 18333882
TI  - Effect of early childhood malnutrition on tooth eruption in Haitian adolescents.
AB  - OBJECTIVE: The objective of this retrospective cohort study was to determine the
      effects of early childhood protein-energy malnutrition (EC-PEM) and current
      nutritional status as defined by anthropomorphic measures on the exfoliation and
      eruption patterns of teeth among adolescents. METHODS: Oral clinical examinations
      were conducted in 2005 using World Health Organization (WHO) diagnostic criteria
      on 498 11- to 13-year-old Haitians for whom early childhood malnutrition data
      were available. Anthropomorphic records (weight-for-age) from the Haitian Health
      Foundation computerized database on children from birth through 5-years old were
      utilized. Current heights and weights were ascertained. Both sets of data were
      converted to z-scores based on the National Center for Health Statistics (NCHS)
      referent database. Based upon these z-scores, EC-PEM and current malnutrition
      categories were developed for this study. The analyses separately regressed the
      number of primary and permanent teeth on age, gender, EC-PEM status and current
      nutritional status. RESULTS: Both a delayed exfoliation of primary teeth and a
      delayed eruption of permanent teeth were associated with EC-PEM and current
      stunting in adolescence. The observed associations were either direct and
      statistically significant or indirectly demonstrated by presenting evidence of
      confounding. The overall interpretation of the models is that malnutrition
      beginning in the earliest years and extending throughout childhood influences the
      exfoliation and eruption of teeth. CONCLUSION: These findings present evidence of
      an association between tooth exfoliation/eruption patterns and both EC-PEM and
      nutritional insufficiency (stunting) throughout childhood. This observed delay in
      the exfoliation of the primary dentition and in the eruption of the permanent
      dentition has practical significance in interpreting age-specific dental caries
      data from populations with different malnutrition experiences.

PMID- 18333883
TI  - Prevalence of RNA polymerase stalling at Escherichia coli promoters after open
      complex formation.
AB  - RNA polymerase (RNAP) trapped in intermediate stages of promoter escape, as well
      as RNAP paused at promoter-proximal sigma(70)-dependent pause sites, gives rise
      to stable, transcriptionally engaged stalled complexes that can limit promoter
      function and present potential sites for transcription regulation. To investigate
      the prevalence of such intermediates, we screened 118 Escherichia coli candidate
      promoters for RNAP stalling at or near the promoter, using in vivo KMnO(4)
      mapping of RNAP on chromosomal DNA. Of 34 active promoters, the seven preceding
      lacZ, tnaA, cspA, cspD, rplK, rpsA and rpsU harboured stalled RNAP in vivo; this
      finding suggests that RNAP stalling after initiation is widespread in E. coli.
      Consistent with the characteristics of both abortive and promoter-proximal
      sigma(70)-dependent paused complexes, RNAP trapping at most of the newly
      identified stall sites was eliminated by the rpoDL402Fsigma(70) mutational
      alteration and by site mutations, and was enhanced by GreA deficiency. In
      addition to promoter-proximal RNAP trapping, we observed transcription-dependent
      DNA modifications spanning the tnaA and cspA leader regions up to 100 bp
      downstream of the transcription start site.

PMID- 18333884
TI  - Involvement of DNA replication in phage lambda Red-mediated homologous
      recombination.
AB  - Crosses between a non-replicating linear bacteriophage lambda chromosome and a
      replicating plasmid bearing a short cloned segment of lambda DNA were monitored
      by extracting DNA from infected cells, and analysing it via restriction
      endonuclease digestion and Southern blots. Recombinant formation resulting from
      the action of the Red homologous recombination system, observed directly in this
      way, was found to be fast, efficient, independent of the bacterial recA function
      and highly dependent upon replication of the target plasmid. These features of
      the experimental system faithfully model Red-mediated recombination in a
      lytically infected cell in which phage DNA replication is occurring. Neither of
      the previously established mechanisms by which the Red system can operate--strand
      annealing or strand invasion--accounts well for these findings. A third
      mechanism, replisome invasion, involving replication directly in the
      recombination mechanism, is invoked as an alternative.

PMID- 18333885
TI  - MSP1(19) miniproteins can serve as targets for invasion inhibitory antibodies in
      Plasmodium falciparum provided they contain the correct domains for cell surface
      trafficking.
AB  - Antibodies from malaria-exposed individuals can agglutinate merozoites released
      from Plasmodium schizonts, thereby preventing them from invading new
      erythrocytes. Merozoite coat proteins attached to the plasma membrane are major
      targets for host antibodies and are therefore considered important malaria
      vaccine candidates. Prominent among these is the abundant
      glycosylphosphatidylinositol (GPI)-anchored merozoite surface protein 1 (MSP1)
      and particularly its C-terminal fragment (MSP1(19)) comprised of two epidermal
      growth factor (EGF)-like modules. In this paper, we revisit the role of
      agglutination and immunity using transgenic fluorescent marker proteins. We
      describe expression of heterologous MSP1(19)'miniproteins' on the surface of
      Plasmodium falciparum merozoites. To correctly express these proteins, we
      determined that GPI-anchoring and the presence of a signal sequence do not allow
      default export of proteins from the endoplasmic reticulum to merozoite surface
      and that extra sequence elements are required. The EGFs are insufficient for
      correct trafficking unless they are fused to additional residues that normally
      reside upstream of this fragment. Antibodies specifically targeting the surface
      expressed miniprotein can inhibit erythrocyte invasion in vitro despite the
      presence of endogenous MSP1. Using a line expressing a green fluorescent protein
      MSP1 fusion protein, we demonstrate that one mode of inhibition by antibodies
      targeting the MSP1(19) domain is the rapid agglutinating of merozoites prior to
      erythrocyte attachment.

PMID- 18333886
TI  - Esterification of cholesterol by a type III secretion effector during
      intracellular Salmonella infection.
AB  - Survival of Salmonella typhimurium within a vacuole in host cells depends on
      secreted virulence factors encoded by the Salmonella pathogenicity island 2 (SPI
      2). High levels of cholesterol are detected at the Salmonella-containing vacuole
      (SCV). Here we show that the SPI-2 effector SseJ esterifies cholesterol in vitro,
      in cells and during infection. Intracellular infections with wild-type as
      compared with DeltasseJ bacteria led to higher levels of cholesterol ester
      production in HeLa cells and RAW macrophages and were shown to increase levels of
      lipid droplets (structures enriched in cholesterol esters). Ectopic expression of
      SseJ reduced cholesterol levels in cellular membranes and antagonized a major
      membrane activity of a second bacterial effector known to be important to the
      stability of the SCV. Previous studies in mouse models of infection have
      established a virulence defect in DeltasseJ bacteria and have suggested a role
      for SseJ in regulating SCV dynamics. Our data indicating the molecular activity
      of SseJ suggest that cholesterol and its esterification at the SCV are
      functionally important for intracellular bacterial survival.

PMID- 18333887
TI  - The contribution of ApoB and ApoA1 measurements to cardiovascular risk
      assessment.
AB  - LDL has been widely recognized as the major atherogenic lipoprotein and
      designated as the primary target for prevention of coronary heart disease (CHD);
      however, there is growing evidence that other triglyceride-rich lipoproteins,
      such as very low-density lipoprotein (VLDL) and intermediate density lipoprotein
      (IDL) carry atherogenic potential as well. This led to the designation of non-HDL
      cholesterol (HDL-C) (LDL + IDL + VLDL) as a secondary target of treatment for
      hyperlipidaemia. As each one of LDL, IDL and VLDL particles carries only one
      apolipoprotein B-100 (ApoB-100) molecule, the total ApoB value represents the
      total number of potentially atherogenic lipoproteins, whereas non-HDL-C provides
      the cholesterol content of these same lipoproteins. Recent data from
      epidemiological, observational and interventional studies suggest that non-HDL-C,
      apolipoproteins ApoA1 and ApoB may improve CHD risk assessment by identifying
      more high-risk individuals than the usual lipid profile alone. However, the
      targets for the optimal treatment of dyslipidaemia remain a subject of
      considerable debate. Further studies are needed to determine whether ApoB and
      ApoA1 are superior to conventional lipid parameters as predictors of
      cardiovascular disease or therapeutic targets of hyperlipidaemias. In this
      review, we summarize the current opinions on the use of ApoA1 and ApoB values as
      estimates of cardiovascular risk or as treatment goals in patients undergoing
      treatment for hyperlipidaemia.

PMID- 18333888
TI  - The dipeptidyl peptidase-4 inhibitor PHX1149 improves blood glucose control in
      patients with type 2 diabetes mellitus.
AB  - AIM: To determine the efficacy and tolerability of PHX1149, a novel dipeptidyl
      peptidase-4 (DPP4) inhibitor, in patients with type 2 diabetes. METHODS: This is
      a multicentre, randomized, double-blind, placebo-controlled, 4-week study in
      patients with type 2 diabetes with suboptimal metabolic control. Patients with a
      baseline haemoglobin A(1c) (HbA(1c)) of 7.3 to 11.0% were randomized 1 : 1 : 1 :
      1 to receive once-daily oral therapy with either PHX1149 (100, 200 or 400 mg) or
      placebo; patients were on a constant background therapy of either metformin alone
      or metformin plus a glitazone. RESULTS: Treatment with 100, 200 or 400 mg of
      PHX1149 significantly decreased postprandial glucose area under the curve AUC(0-2
      h) by approximately 20% (+0.11 +/- 0.50, -2.08 +/- 0.51, -1.73 +/- 0.49 and -1.88
      +/- 0.48 mmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p =
      0.002, 0.008 and 0.004 vs. placebo). Postprandial AUC(0-2 h) of intact glucagon
      like peptide-1, the principal mediator of the biological effects of DPP4
      inhibitors, was increased by 3.90 +/- 2.83, 11.63 +/- 2.86, 16.42 +/- 2.72 and
      15.75 +/- 2.71 pmol/l x h, respectively, for placebo and 100, 200 and 400 mg (p =
      0.053, 0.001 and 0.002 vs. placebo). Mean HbA(1c) was lower in all dose groups;
      the placebo-corrected change in the groups receiving 400 mg PHX1149 was -0.28% (p
      = 0.02). DPP4 inhibition on day 28 was 53, 73 and 78% at 24 h postdose in the
      groups receiving 100, 200 and 400 mg PHX1149, respectively. There were no
      differences in adverse events between PHX1149-treated and placebo subjects.
      CONCLUSIONS: Addition of the DPP4 inhibitor PHX1149 to a stable regimen of
      metformin or metformin plus a glitazone in patients with type 2 diabetes was well
      tolerated and improved blood glucose control.

PMID- 18333889
TI  - Combination of the insulin sensitizer, pioglitazone, and the long-acting GLP-1
      human analog, liraglutide, exerts potent synergistic glucose-lowering efficacy in
      severely diabetic ZDF rats.
AB  - OBJECTIVE: Severe insulin resistance and impaired pancreatic beta-cell function
      are pathophysiological contributors to type 2 diabetes, and ideally,
      antihyperglycaemic strategies should address both. RESEARCH DESIGN AND METHODS:
      Therapeutic benefits of combining the long-acting human glucagon-like peptide-1
      (GLP-1) analog, liraglutide (0.4 mg/kg/day), with insulin sensitizer,
      pioglitazone (10 mg/kg/day), were assessed in severely diabetic Zucker diabetic
      fatty rats for 42 days. Impact on glycaemic control was assessed by glycated
      haemoglobin (HbA(1C)) at day 28 and by oral glucose tolerance test at day 42.
      RESULTS: Liraglutide and pioglitazone synergistically improved glycaemic control
      as reflected by a marked decrease in HbA(1C) (liraglutide + pioglitazone: 4.8 +/-
      0.3%; liraglutide: 8.8 +/- 0.6%; pioglitazone: 7.9 +/- 0.4%; vehicle: 9.7 +/-
      0.3%) and improved oral glucose tolerance at day 42 (area under the curve;
      liraglutide + pioglitazone: 4244 +/- 445 mmol/l x min; liraglutide: 7164 +/- 187
      mmol/l x min; pioglitazone: 7430 +/- 446 mmol/l x min; vehicle: 8093 +/- 139
      mmol/l x min). A 24-h plasma glucose profile at day 38 was significantly
      decreased only in the liraglutide + pioglitazone group. In addition, 24-h insulin
      profile was significantly elevated only in the liraglutide + pioglitazone group.
      Liraglutide significantly decreased food intake alone and in combination with
      pioglitazone, while pioglitazone alone increased cumulated food intake. As a
      result, rats on liraglutide alone gained significantly less weight than vehicle
      treated rats, whereas rats on pioglitazone alone gained significantly more body
      weight than vehicle-treated rats. However, combination therapy with liraglutide
      and pioglitazone caused the largest weight gain, probably reflecting marked
      improvement of energy balance because of reduction of glucosuria. CONCLUSIONS:
      Combination therapy with insulinotropic GLP-1 agonist liraglutide and insulin
      sensitizer, pioglitazone, improves glycaemic control above and beyond what would
      be expected from additive effects of the two antidiabetic agents.

PMID- 18333890
TI  - Thiazolidinedione insulin sensitizers and the heart: a tale of two organs?
AB  - Thiazolidinediones (TZDs) are relatively new agents for the treatment of type 2
      diabetes. They act as agonists at the PPAR-gamma nuclear receptor and their
      therapeutic effects include decreased insulin resistance and hyperglycaemia, an
      improved plasma lipid, inflammation and pro-coagulant profile, and amelioration
      of hypertension, microalbuminuria and hepatic steatosis. The most common side
      effects of TZDs include weight gain and oedema, with occasional reports of
      congestive heart failure (CHF). This review discusses the benefit-risk profile of
      TZDs in treating patients with type 2 diabetes, with particular reference to the
      heart. To provide context, we explore briefly the epidemiology and
      pathophysiology of heart failure in patients with type 2 diabetes, touch on the
      association of heart disease and cardiovascular mortality with antihyperglycaemic
      treatment modalities other than TZDs, and then focus on the effects of TZDs on
      the heart, cardiovascular risk factors and outcomes. We describe the cluster of
      host factors, which seems to predispose patients with type 2 diabetes to TZD
      induced or TZD-exacerbated oedema and CHF and then provide an overview of the
      putative mechanisms of these TZD-related side effects. We also propose that
      certain diuretics (amiloride and spironolactone), by targeting the distal nephron
      that expresses PPARgamma in collecting duct cells, might be of benefit in
      ameliorating the fluid retention and oedema associated with TZDs.

PMID- 18333891
TI  - Continuous subcutaneous insulin infusion leads to immediate, stable and long-term
      changes in metabolic control.
AB  - BACKGROUND: Evaluations of continuous subcutaneous insulin infusion (CSII)
      usually focus on one pre- and one post-CSII measurement to assess metabolic
      therapy outcome. AIM: Extending this research, the aim of the present study was
      to provide a more fine-grained analysis of achieved glycaemic control. METHODS:
      In 52 patients with type 1 diabetes (mean age of 37.85 years at CSII begin; s.d.
      +/- 12.41), haemoglobin A(1c) (HbA(1c)) levels were assessed every 3 months over
      a period of 5 years (1 year before and 4 years after the introduction of CSII).
      Mixed models were utilized to describe changes in glycaemic control. RESULTS: The
      pre-post course showed that already in the first quarter, a statistically
      significant lower HbA(1c) level was obtained [7.30%, in contrast to 8.21% at the
      last quarter with intensified conventional therapy (ICT)]. In the following 15
      quarters, the mean HbA(1c) levels remained constantly lower than that with ICT.
      Overall, the aggregated mean HbA(1c) level of patients with CSII therapy was
      7.19%, in contrast to 8.08% with ICT; thus, an overall decrease by 11% was
      achieved. In addition, individual differences in blood glucose level and age of
      diabetes onset as a predictor for therapy success were analysed. CONCLUSIONS: The
      data show an immediate, stable and long-term effect of CSII on HbA(1c). In
      addition, a significant relationship between metabolic control and age of
      diabetes onset was found, as well as a reduction of variance in HbA(1c) levels
      between subjects after change to CSII.

PMID- 18333892
TI  - Daily administration of the GIP-R antagonist (Pro3)GIP in streptozotocin-induced
      diabetes suggests that insulin-dependent mechanisms are critical to anti-obesity
      diabetes actions of (Pro3)GIP.
AB  - AIM: Glucose-dependent insulinotropic polypeptide-receptor (GIP-R) antagonism
      using (Pro3)GIP improves glucose tolerance and ameliorates insulin resistance and
      abnormalities of islet structure and function in a commonly used model of obesity
      diabetes, namely ob/ob mice. The effect of GIP-R antagonism in a streptozotocin
      (STZ)-induced model of insulin deficiency has not been evaluated. The present
      study has investigated the effects of daily administration of (Pro(3))GIP to STZ
      treated mice. METHODS: Swiss TO mice received once-daily injection of (Pro3)GIP
      (25 nmol/kg body weight) or saline 4 days prior to and 16 days after injection of
      STZ, and effects on metabolic parameters and islet architecture were assessed.
      RESULTS: (Pro3)GIP treatment had no significant effect on hyperphagia or body
      weight loss. However, hyperglycaemia and glycated haemoglobin were worsened,
      glucose tolerance further decreased and insulin sensitivity was impaired by
      (Pro3)GIP. These effects were observed on an STZ-induced background characterized
      by severe reductions of circulating insulin, beta-cell mass and pancreatic
      insulin stores. CONCLUSIONS: These data indicate that the beneficial actions of
      the GIP-R antagonist, (Pro3)GIP, in obesity-diabetes appear to be largely
      mediated through insulin-dependent mechanisms that merit further investigation.

PMID- 18333893
TI  - Resveratrol blocks high glucose-induced mitochondrial reactive oxygen species
      production in bovine aortic endothelial cells: role of phase 2 enzyme induction?

PMID- 18333894
TI  - Discordance in the histopathologic diagnosis of difficult melanocytic neoplasms
      in the clinical setting.
AB  - BACKGROUND: The gold standard for diagnosing melanocytic neoplasms is by
      histopathologic examination. However, lack of agreement among expert
      dermatopathologists in evaluating these tumors has been well established in
      experimental settings. OBJECTIVE: This study examines the discordance among
      dermatopathologists in evaluating difficult melanocytic neoplasms in a clinical
      setting where the diagnosis impacts patient management. METHODS: Retrospective
      review of consultation reports over a 6-year period. RESULTS: There was complete
      agreement among the consultants in 54.5% of the cases. However, a high level of
      disagreement was found in 25% of the cases. LIMITATIONS: The analysis was limited
      to two consultant dermatopathologists. CONCLUSIONS: There are limitations to the
      practical applications of histologic criteria for diagnosing difficult
      melanocytic tumors. It is not malpractice for a pathologist to have rendered a
      diagnosis that did not predict clinical outcome as long as 'standard of care' has
      been followed in his/her evaluation of the specimen.

PMID- 18333895
TI  - Squamous cell carcinomas with single cell infiltration: a potential diagnostic
      pitfall and the utility of MNF116 and p63.
AB  - Numerous variants of squamous cell carcinoma (SCC) have been described. We
      recently encountered four examples of SCC composed primarily of single, atypical
      cells that were cytokeratin (CK) MNF116-positive and p63-positive. One case was
      particularly difficult to diagnose as the single cells were obscured by a dense
      inflammatory infiltrate. We have also noted similar single cell infiltration
      toward the periphery of four additional cases of more typical SCC. These foci
      resemble the single tumor cells that may infiltrate at the borders of spindle
      cell and desmoplastic SCCs. CK MNF116 and p63 were useful in identifying each of
      these neoplasms. This single--cell pattern of SCC can easily be misdiagnosed, and
      CK MNF116 and/or p63 are diagnostically helpful in recognizing it.

PMID- 18333896
TI  - Ber-EP4 enhances the differential diagnostic accuracy of cytokeratin 7 in
      pagetoid cutaneous neoplasms.
AB  - BACKGROUND: While cytokeratin 7 is a reliable marker for most cases of Paget's
      disease, it is not 100% sensitive. Moreover, cases of cytokeratin 7-positive
      pagetoid squamous cell carcinoma in situ are reported in the literature. The
      monoclonal antibody Ber-EP4 is diagnostically highly reliable in the
      differentiation between basal cell carcinoma and cutaneous squamous cell
      carcinoma. Here we report its application in the differential diagnosis of
      cutaneous pagetoid neoplasms. METHODS: Biopsy samples from 21 cases of
      extramammary Paget's disease, 12 pagetoid squamous cell carcinomas in situ and 10
      pagetoid melanomas in situ of the superficial spreading type were examined
      immunohistochemically with Ber-EP4, 34betaE12 and HMB-45. RESULTS: Ber-EP4
      selectively labeled all cases of extramammary Paget's disease but none of the
      other pagetoid neoplasms. The majority of cases (18 = 85.7%) displayed strong and
      three (14.3%) showed moderate immunoreactivity. CONCLUSIONS: Ber-EP4 reliably
      differentiates extramammary Paget's disease from pagetoid squamous cell carcinoma
      in situ and pagetoid melanoma in situ. The antibody should be included along with
      a panel of other markers when evaluating for pagetoid cutaneous neoplasms in
      order to avoid a possible misdiagnosis of pagetoid squamous cell carcinoma in
      situ.

PMID- 18333897
TI  - SOX9 expression is a general marker of basal cell carcinoma and adnexal-related
      neoplasms.
AB  - BACKGROUND: SOX9 is a transcription factor that fulfills multiple functions
      during development. In the hair follicle SOX9 is expressed in the outer layer of
      the epithelial sheath, and the hair stem cell compartment. Recent data suggest
      that Sox9 acts as a downstream target of the Sonic hedgehog (Shh) pathway.
      Activation of the Shh pathway is a major cause of cutaneous basal cell carcinoma
      (BCC). Here we test whether activation of SOX9 is a general feature of BCC, or
      whether it could be used as a biomarker to better define subtypes of these skin
      tumors. In addition we investigated SOX9 expression in other skin epidermal
      tumors. METHODS: Tumors sections were stained with hematoxylin & eosin (H&E).
      SOX9 activation was determined by immunofluorescence. RESULTS: SOX9 activation
      was observed in all subtypes of BCC tested. Staining was heterogeneous and could
      be detected among the basaloid cells of the palisading cell layer as well as in
      the tumour nest. SOX9 expression was detected in all adnexal tumors analyzed and
      absent in Bowen's disease and Merkel tumor. CONCLUSIONS: SOX9 expression is a
      general feature of BCC and adnexal skin neoplasms, suggesting a contribution of
      SOX9 to the pathogenesis of these tumors.

PMID- 18333898
TI  - The cutaneous manifestations of atypical complete DiGeorge syndrome: a
      histopathologic and immunohistochemical study.
AB  - DiGeorge syndrome is a congenital anomaly with a constellation of findings that
      includes thymic hypoplasia. Only a small subset of patients with DiGeorge
      syndrome has complete athymia, classified as complete DiGeorge anomaly; one third
      of these patients show an eczematous dermatitis, oligoclonal T-cells and
      lymphadenopathy, known as atypical complete DiGeorge anomaly. Six biopsies from
      six patients with the distinctive clinical phenotype of atypical complete
      DiGeorge anomaly were studied. Every biopsy showed exocytosis (100%),
      parakeratosis, often confluent and spongiosis (100%). Neutrophilic abscesses
      (50%), dyskeratosis (67%) and satellite cell necrosis (50%) were seen.
      Perieccrine and perivascular inflammation were seen in half of the cases.
      Eosinophils were identified (83%); most commonly in both the epidermis and
      dermis. All of lymphocytes were CD3 positive. Most (83%) of cases contained T
      cell intracellular antigen 1 (TIA-1) positive cells. Special testing of the
      selected patients using spectratyping identified oligoclonal T-cell populations.
      The presence of dyskeratotic keratinocytes, satellite cell necrosis and
      parakeratotic scale with neutrophils characterizes the cutaneous rash seen in
      this subset of complete DiGeorge syndrome patients. Such skin lesions from
      patients with DiGeorge anomaly should alert the pathologist to the potential
      diagnosis of atypical complete DiGeorge anomaly. The pathophysiologic role of the
      oligoclonal T-cells in this entity requires additional study.

PMID- 18333899
TI  - Diagnostic concordance among dermatopathologists using a three-tiered
      keratinocytic intraepithelial neoplasia grading scheme.
AB  - The distinction between actinic keratosis (AK) and squamous cell carcinoma in
      situ (SCCIS) is a subject of discussion among dermatopathologists. A previous
      study determined that there was excellent interobserver agreement among
      dermatopathologists using the current two-tiered grading system. Presently, we
      assessed concordance among dermatopathologists using a three-tiered keratinocytic
      intraepithelial neoplasia (KIN) diagnostic system. At the 2006 meeting of the
      American Society of Dermatopathology (ASDP), registration personnel solicited 125
      registrants by randomly inserting an invitation into 125 registration packets.
      Participants reviewed 15 glass slides representing a spectrum of keratinocytic
      atypia from AK to SCCIS. Participants were asked to choose 1 or 2 but not 3
      grades of KIN that best reflected the changes on each slide. Thirty-two of the
      125 solicited enrollees participated in the study. There were 16 volunteers for a
      total of 48 participants. The inter-observer agreement for all participants was
      0.575 (moderate agreement). The overall inter-observer agreement for anatomic
      pathologist-dermatopathologists (AP-DP), dermatopathologist-dermatologists (DP-D)
      and anatomic pathologist-dermatologist-dermatopathologists (AP-DP-D) was 0.665,
      0.609 and 0.670 (substantial agreement), respectively. There is high concordance
      among dermatopathologists using a three-tiered diagnostic system for KIN. The
      observed agreement suggests that dermatopathologists are reliably able to
      categorize the continuum of keratinocytic atypia in a manner that may have
      diagnostic relevance.

PMID- 18333900
TI  - Oral mucosal melanoma with unusual clinicopathologic features.
AB  - Oral mucosal melanoma (OMM) is an extremely rare malignancy, accounting for <
      0.5% of all melanomas and all oral malignancies. The rarity of OMM, the
      heterogeneity in clinical and histopathologic appearances, and the paucity of
      molecular and genetic studies to date have limited our knowledge of the
      etiopathogenesis of these cancers. A 39-year-old Hispanic male presented for
      evaluation of a large, pigmented, plaque-like and nodular growth of the maxillary
      gingival and palatal mucosa. On presentation, a presumptive clinical diagnosis of
      mucosal melanoma was made, which was confirmed by incisional biopsy with
      subsequent histopathologic evaluation. Macroscopically, the morphology and highly
      pigmented nature of the tumor was suggestive of a rarer subtype of melanoma known
      as animal-type melanoma, also referred to as pigmented epithelioid melanocytoma.
      However, microscopically, the tumor showed histopathologic features consistent
      with a high-grade acral (mucosal) lentiginous melanoma with overt cytomorphologic
      features of malignancy in addition to showing prominent pigment synthesis
      resembling animal-type melanoma. A detailed search of the literature did not
      identify a previous report of OMM with prominent pigment synthesis resembling
      animal-type melanoma. Identification of melanoma subtypes has specific
      implications for therapeutic approach, and thus their recognition is important to
      successful patient management.

PMID- 18333901
TI  - Histopathologic findings and diagnostic difficulties posed with use of escharotic
      agents for treatment of skin lesions: a case report and review of the literature.
AB  - Escharotic agents have been used as alternative therapy for treatment of skin
      cancer and skin problems for centuries. Internet web sites such as online health
      product stores and eBay have made them widely available to the general public.
      The use of these agents carries risk of incomplete removal of tumor, damage of
      surrounding healthy tissues and marked scarring with poor cosmetic outcome. We
      report the case of a 27-year-old man who presented with history of moles and self
      treatment with an escharotic agent containing bloodroot in order to document the
      histopathologic findings of topical bloodroot treatment and to show the clinical
      consequences that may occur in the unsuspecting public. To the best of our
      knowledge, the histological features following use of bloodroot (Sanguinaria
      canadensis) have not yet been documented.

PMID- 18333902
TI  - Lobular panniculitis at the site of glatiramer acetate injections for the
      treatment of relapsing-remitting multiple sclerosis. A report of two cases.
AB  - Lipoatrophy and localized panniculitis have been described as rare complications
      of daily subcutaneous glatiramer acetate injections for the treatment of
      relapsing-remitting multiple sclerosis (MS). We describe the biopsies from two MS
      patients in a single neurologist's practice who developed clinical lesions of
      lipoatrophy at the sites of subcutaneous glatiramer acetate injections. These
      biopsies showed a lobular panniculitis with lipoatrophy that more closely
      resembled lupus panniculitis than previous reports of localized panniculitis at
      glatiramer acetate injection sites. In one case, the area of clinical lipoatrophy
      continued to enlarge for 6 months after stopping glatiramer acetate therapy,
      before stabilizing at its current size for the last 8 months. Injection site
      reactions to glatiramer acetate should be considered in the differential
      diagnosis of biopsies that show a lupus panniculitis-like appearance. Our
      observations indicate that glatiramer acetate induced panniculitis is common and
      may continue to progress after therapy has stopped. In this single neurologist's
      practice, 64% of the patients receiving daily glatiramer acetate injections had
      clinical evidence of lipoatrophy or panniculitis. Of 100 consecutive patients
      receiving therapy for MS between February and November 2006, 14 patients were on
      glatiramer acetate, 9 of whom had clinical lipoatrophy.

PMID- 18333903
TI  - Clear cell sarcoma of soft tissue: diagnostic utility of fluorescence in situ
      hybridization and reverse transcriptase polymerase chain reaction.
AB  - A 7-year-old girl presented with pain and progressive swelling on the left
      plantar surface. Biopsy of a 2.5 cm mass showed nests of large round to oval
      neoplastic cells with abundant amphophilic to clear cytoplasm, prominent nucleoli
      and high mitotic activity. Occasional cells showed spindled morphology.
      Infrequent melanin pigment was present. Melanocytic markers (HMB45, S-100) were
      diffusely positive. A diagnosis of clear cell sarcoma of soft tissue (CCSS) was
      made, and the mass was re-excised with negative margins. 28 months later, a 1.0
      cm pulmonary nodule was identified and wedge excision showed metastatic CCSS.
      Cytogenetics showed a complex karyotype (unbalanced translocation
      der(12;14)(q10;q10), additional chromosome 22 material of unknown origin).
      Although the CCSS translocation t(12;22)(q13;q12) was not identified, EWSR1 gene
      rearrangement was detected by fluorescence in situ hybridization (FISH). Reverse
      transcription polymerase chain reaction (RT-PCR) showed an EWS-ATF1 fusion
      transcript, confirmed by direct sequencing. CCSS requires differentiation from
      malignant melanoma, because of overlapping clinical presentations, sites of
      involvement, histomorphology, immunocytochemical profiles and ultrastructure. In
      many circumstances, definitive diagnosis is only possible with confirmation of
      the CCSS-defining translocation.

PMID- 18333904
TI  - Skin metastasis from typical carcinoid tumor of the lung.
AB  - Carcinoids are neuroendocrine tumors that may arise within any organ, although
      they are more commonly found in the gastrointestinal tract and in the
      bronchopulmonary tract. They are generally characterized by an indolent clinical
      course but may in some instances metastatise to regional lymph nodes or to
      distant sites. We herein describe a rather infrequent case of a 60-year-old man
      with a skin metastasis from a typical carcinoid of the lung. We discuss the
      histopathological and immunohistochemical features in the context of previous
      literature and comment issues related to difficulties in the differential
      diagnosis. Dermatopathologists should be familiar with the metastatic carcinoid
      profile in order to avoid potential misdiagnoses and to properly address the
      patient management when the skin metastasis represents the first manifestation of
      an internal disease.

PMID- 18333905
TI  - Atypical distinctive dermal clear cell mesenchymal neoplasm arising in the scalp.
AB  - Distinctive dermal clear cell mesenchymal neoplasm (DDCCMN) is a newly described
      entity characterized by a dermal proliferation of neoplastic cells with clear to
      reticulated cytoplasm and vesicular nuclei. Atypical features in the form of
      nuclear pleomorphism and mitoses may be found. The histogenesis of these
      neoplastic clear cells is not currently known but they are thought to be
      mesenchymal in origin. Immunohistochemically, they stain positively for NKI-C3
      and negatively for melanocytic, epithelial and lymphoid markers. All five cases
      originally reported by Lazar and Fletcher occurred in the lower extremities. We
      report herein a case of DDCCMN with atypical features arising in the scalp.

PMID- 18333906
TI  - Collagenous spherulosis in an oral mucous cyst.
AB  - Collagenous spherulosis is a histological pattern that has been described in both
      benign and malignant salivary gland tumors, proliferative lesions of breast
      ductal epithelium, chondroid syringomas and schwannomas. Histologic structures of
      similar appearance have also been reported in oral extravasation mucoceles as
      questionable myxoglobulosis or myxoglobulosis-like change. We report collagenous
      spherulosis within a mucocele removed from the lower lip of a 17-year-old female.
      Based upon histologic appearance, immunophenotypic data and review of the
      literature, we hypothesize that collagenous spherulosis and myxoglobulosis are
      morphologically related reaction patterns.

PMID- 18333907
TI  - Looking back, heading forward.

PMID- 18333908
TI  - 2007 IXA Presidential Address. Progress toward an ideal source animal:
      opportunities and challenges in a changing world.
AB  - Xenotransplantation holds great promise for the treatment of end-stage organ
      failure and tissue injury. Recent advances in our understanding of the
      immunological hurdles to xenotransplantation and the development of genetic
      modification approaches to overcome them increase the likelihood of success.
      Exciting advances in these areas were presented at the Joint Congress of the IXA,
      the Cell Transplant Society and the International Pancreas and Islet Transplant
      Association in Minneapolis in September, 2007. However, in order to minimize
      infectious risks and encourage positive public perception of xenotransplantation,
      clinical trials should be initiated with appropriate monitoring and oversight
      procedures in place and only when there is high expectation of clinical benefit.

PMID- 18333909
TI  - Studies of monkey complement: measurement of cynomolgus monkey CH50, ACH50, C4,
      C2 and C3.
AB  - BACKGROUND: The cynomolgus monkey is commonly used as the recipient in
      transplantation experiments. However, study of the complement system of
      cynomolgus monkeys is lacking. In the present study, the complement system of
      cynomolgus monkeys was compared with that of humans, by checking hemolytic
      titers. METHODS: Hemolytic titers of complement from cynomolgus monkeys were
      calculated using the same methods as are used in humans. The complement
      regulatory function of human decay accelerating factor (DAF, CD55) in cynomolgus
      monkey serum was next studied using erythrocytes from human DAF-transgenic pigs.
      RESULTS: The results indicated relatively high values, except for C4: CH50:
      211.19 +/- 42.78 units/ml, ACH50: 51.47 +/- 12.43 units/ml, C4: 30 170 +/- 14 300
      SFU/ml C2: 33831 +/- 7442 SFU/ml and C3: 93612 +/- 30131 SFU/ml. Western blot
      experiments using antibodies for human complement components revealed
      similarities between the cynomolgus monkey and human complement systems. Human
      DAF inhibited pig erythrocyte lysis from approximately 60-70% to 17% in both
      human and cynomolgus monkey sera, indicating an almost identical complement
      regulatory function. CONCLUSION: The hemolytic titer of cynomolgus monkeys was
      greater than the titer measured in human serum. However, human DAF showed nearly
      the same complement regulatory function in both human and cynomolgus monkey sera.

PMID- 18333910
TI  - Anti-Gal antibody-mediated skin graft rejection requires a threshold level of Gal
      expression.
AB  - BACKGROUND: Despite overcoming xenograft hyperacute rejection (HAR), Gal
      (galactose-alpha1,3-galactose) expression may not be completely eliminated from
      the alpha1,3-galactosyltransferase gene knockout (Gal KO) pig because of
      alternative galactosyltransferases. Whether low levels of "residual" Gal are
      still susceptible to either complement fixing or non-complement fixing antibody
      beyond the HAR barrier remains unknown. Furthermore, it would be impossible to
      analyze the immune response specific to low-level Gal in a xenograft setting
      given the multitude of xenoantigens that could induce a recipient response. To
      investigate this question, we therefore used a skin graft model in BALB/c mice
      where the sole difference between donor and recipient was the expression of Gal,
      where rejection is caused by passively administered anti-Gal monoclonal antibody
      and where HAR does not occur. METHODS: Gal expression over time was examined by
      immunohistochemistry in wildtype-to-Gal KO skin grafts. Graft rejection in
      response to passively administered anti-Gal monoclonal antibody at early and late
      time points was studied to determine changes in susceptibility to antibody. To
      independently test the effect of reduced Gal expression on antibody-mediated
      rejection, we used two separate lines of alpha1,2-fucosyltransferase transgenic
      mice as skin donors in the model. These mice have known reduced but different
      levels of Gal as determined by flow cytometry on peripheral blood leukocytes.
      RESULTS: Gal expression on skin grafts diminished with time with a corresponding
      reduction in susceptibility to antibody-mediated rejection. Skin grafts at day 30
      (n = 7) and 150 (n = 11) had a rejection rate of 100% and 45% respectively in
      response to non-complement fixing anti-Gal antibody administered to the
      recipient. Similar results were demonstrated with a complement fixing anti-Gal
      antibody. When alpha1,2-fucosyltransferase transgenic mice skin was used in the
      model, the line with lowest level of Gal expression was resistant to antibody
      induced rejection with a rate 0% (n = 9) vs. 60% (n = 5) in the alternative line
      with relatively more Gal expressed but still much less than normal mice.
      CONCLUSIONS: Resistance to anti-Gal antibody-mediated damage in the model was
      observed in skin grafts 100 to 150 days post-grafting but not earlier and was
      associated with a reduction in Gal expression. It is possible that below a
      threshold level of Gal expression, the grafts were not susceptible to anti-Gal
      antibody.

PMID- 18333911
TI  - Pre-treatment of porcine pulmonary xenograft with desmopressin: a novel strategy
      to attenuate platelet activation and systemic intravascular coagulation in an ex
      vivo model of swine-to-human pulmonary xenotransplantation.
AB  - BACKGROUND: Von Willebrand factor (vWF) has been proposed as a major contributor
      to the development of coagulopathy in pulmonary xenotransplantation. Pretreatment
      of donor swine with 1-deamino-8-d-arginine vasopressin (DDAVP), an analog of
      vasopressin, can reduce the content of vWF in pulmonary xenografts. Here, we
      investigate the effects of DDAVP pre-treatment in an ex-vivo perfusion model of
      pulmonary xenotransplantation. METHODS: We set up and performed the ex-vivo
      perfusion using porcine pulmonary accessory lobes and fresh human whole blood (n
      = 12). Half of the donor swine were given 3 mug/kg DDAVP intravenously for 3 days
      before ex-vivo perfusion (DDAVP group) and half of them were left untreated
      (control group). The porcine lung was perfused with fresh blood for 1 h and
      changes in the following parameters were monitored: pulmonary arterial pressure,
      pulmonary vascular resistance, blood cell counts, fibrinogen, antithrombin,
      platelet factor 4, D-dimer, C3a, C4d, and xenoreactive IgM. The release of
      Galalpha1-3Gal xenoantigen (alphaGal) from porcine lung which had been perfused
      and retained for 30 min with human blood was assessed by enzyme-linked
      immunosorbent assay using alphaGal-binding lectin. RESULTS: Both DDAVP and
      control groups showed typical findings of immediate pulmonary dysfunction: an
      increase of pulmonary vascular resistance and sequestration of leukocytes and
      platelets after ex-vivo perfusion. However, in the DDAVP group, the increase of
      platelet factor 4, C3a, and C4d after perfusion was attenuated compared to that
      in the control group. The release of alphaGal after blood retention was
      significantly lower in the DDAVP group than that of the control group.
      CONCLUSION: Pre-infusion of DDAVP to the donor swine was beneficial in
      attenuating platelet activation as well as complement/coagulation activation.
      These effects of DDAVP are likely to relate to the reduction of porcine vWF
      content in the xenograft. Therefore, the modulation of vWF secretion in donor
      lungs could be an additional therapeutic way to reduce systemic coagulopathy in
      pulmonary xenotransplantation.

PMID- 18333912
TI  - Knockdown of porcine endogenous retrovirus (PERV) expression by PERV-specific
      shRNA in transgenic pigs.
AB  - BACKGROUND: Xenotransplantation using porcine cells, tissues or organs may be
      associated with the transmission of porcine endogenous retroviruses (PERVs). More
      than 50 viral copies have been identified in the pig genome and three different
      subtypes of PERV were released from pig cells, two of them were able to infect
      human cells in vitro. RNA interference is a promising option to inhibit PERV
      transmission. METHODS: We recently selected an efficient si (small interfering)
      RNA corresponding to a highly conserved region in the PERV DNA, which is able to
      inhibit expression of all PERV subtypes in PERV-infected human cells as well as
      in primary pig cells. Pig fibroblasts were transfected using a lentiviral vector
      expressing a corresponding sh (short hairpin) RNA and transgenic pigs were
      produced by somatic nuclear transfer cloning. Integration of the vector was
      proven by PCR, expression of shRNA and PERV was studied by in-solution
      hybridization analysis and real-time RT PCR, respectively. RESULTS: All seven
      born piglets had integrated the transgene. Expression of the shRNA was found in
      all tissues investigated and PERV expression was significantly inhibited when
      compared with wild-type control animals. CONCLUSION: This strategy may lead to
      animals compatible with PERV safe xenotransplantation.

PMID- 18333913
TI  - Effects of pharmacological intervention on coagulopathy and organ function in
      xenoperfused kidneys.
AB  - BACKGROUND: Following pig to primate kidney transplantation, xenogenic activation
      of the coagulation (XAC) system of the recipient eventually leading to organ
      dysfunction and disseminated intravascular coagulation (DIC) can be observed.
      METHODS: Using an ex-vivo perfusion circuit based on low-dose heparin-mediated
      anticoagulation and exogenous complement inhibition by C1- Inhibitor (C1-Inh), we
      have analysed XAC following contact of human blood with porcine endothelium.
      Porcine kidneys (n = 23) were recovered following in situ cold perfusion with
      histidine-tryptophan-ketoglutarate (HTK) solution and were connected to a
      perfusion circuit utilizing freshly drawn pooled human AB blood. RESULTS: Kidney
      survival during organ perfusion with human blood, CI-Inh, heparin but without any
      further pharmacological intervention was 126 +/- 78 min. XAC was observed with
      significantly elevated levels of D-dimer and thrombin antithrombin complexes
      (TAT). Pharmacological intervention with nitroprusside and prostacycline resulted
      in increased organ survival (220 +/- 28 min and 180 +/- 85 min respectively) but
      failed to inhibit XAC. In contrast, addition of activated protein C (APC)
      significantly reduced the increase in D-dimer and TAT and prolonged organ
      survival to 240 min (+/-0). On histology, no remarkable signs of XAC were
      observed. CONCLUSIONS: We conclude that exogenous APC is able to reduce XAC in
      this ex vivo perfusion model.

PMID- 18333914
TI  - Adoptive transfer of double negative T regulatory cells induces B-cell death in
      vivo and alters rejection pattern of rat-to-mouse heart transplantation.
AB  - BACKGROUND: Antibody-mediated hyperacute and acute graft rejection are major
      obstacles in achieving long-term graft survival in xenotransplantation. It is
      well documented that regulatory T (Treg) cells play a very important role in
      regulating immune responses to self and non-self antigens. Our previous studies
      have shown that TCRalphabeta+CD3+CD4-CD8- (double negative, DN)-Treg cells can
      suppress anti-donor T-cell responses and prolong graft survival in allo- and
      xenotransplantation models. We have demonstrated that DN-Treg cells can induce B
      cell apoptosis in vitro through a perforin-dependent pathway. METHODS: B6 mice
      received rat heart grafts, followed by 14 days of LF15-0195 treatment. Some mice
      received Lewis rat cell activated DN-Treg cells after LF treatment. DN-Treg
      cells, purified from perforin-/- mice and from B6 mice pre-immunized with third
      party rat cells, were used as controls. RESULTS: In this study, we investigated
      the possibility that adoptive transfer of xenoreactive DN-Treg cells could
      suppress B cells in vivo, thus prolonging xenograft survival. We found that
      apoptotic death of B cells significantly increased after adoptive transfer of DN
      Treg cells. In addition, anti-donor IgG subtypes were significantly inhibited in
      the DN-Treg cell-treated group, in which the rejection pattern was altered
      towards cellular-mediated rejection rather than antibody-mediated acute vascular
      rejection. However, perforin-deficient DN-Treg cells failed to induce B-cell
      death and to prolong heart graft survival, indicating a perforin-dependent
      mechanism contributes to B-cell death in vivo. CONCLUSIONS: This study suggests
      that adoptive transfer of xenoreactive DN-Treg cells can inhibit B-cell responses
      in vivo. DN-Treg cells may be valuable in controlling B-cell responses in
      xenotransplantation.

PMID- 18333915
TI  - Xenotransplantation literature update September-October, 2007.

PMID- 18333916
TI  - Eosinophilic bronchitis-like lesion as the cause of death in a Macaca mulatta: a
      first case report.
AB  - BACKGROUND: Eosinophilic bronchitis is a recently described, relatively benign
      condition in humans that is characterized by a corticosteroid-responsive chronic
      cough and sputum eosinophilia without the abnormalities of airway function seen
      in asthma. The exact cause of this condition is currently unknown, however has
      been associated with various occupational exposures in humans. It has also been
      reported to progress to irreversible airway obstruction. This disease has been
      reported in dogs and horses, but not in non-human primates. METHODS: Gross
      examination of an otherwise healthy 13-year-old, colony-born Macaca mulatta,
      which died of severe non-responsive respiratory distress revealed that the lungs
      were markedly inflated and moist. RESULTS: Hematoxylin and eosin-stained sections
      from the lungs contained widespread accumulation of eosinophils, sloughed
      epithelial cells, and mucus centered around bronchioles and adjacent airways.
      There was no evidence of mast cell infiltration of peribronchiolar smooth muscle,
      goblet cell hyperplasia, or basement membrane thickening. CONCLUSIONS: This ruled
      out recurrent episodes as would be expected in asthma, favoring the diagnosis of
      an eosinophilic bronchitis-like lesion. We report a first case of eosinophilic
      bronchitis-like features in a M. mulatta.

PMID- 18333917
TI  - Genetic characterization of wild and captive rhesus macaques in China.
AB  - The genetic structures of wild and captive rhesus macaque populations within
      China were compared by analyzing the mtDNA sequences of 203 captive-bred Chinese
      rhesus macaques with 77 GenBank sequences from wild-caught animals trapped
      throughout China. The genotypes of 22 microsatellites of captive Chinese rhesus
      macaques were also compared with those of captive Indian animals. The Chinese
      population is significantly differentiated from the Indian population and is more
      heterogeneous. Thus, compared with Indian rhesus macaques the phenotypic variance
      of traits with high heritability will be inflated in Chinese animals. Our data
      suggest that the western Chinese provinces have more subdivided populations than
      the eastern and southern Chinese provinces. The southern Chinese populations are
      the least structured and might have been more recently established. Human
      mediated interbreeding among captive Chinese populations has occurred, implying
      that Chinese breeding strategies can influence the interpretation of biomedical
      research in the USA.

PMID- 18333918
TI  - Biochemical and white blood cell profiles of baboon neonates consuming formulas
      with moderate and high dietary long-chain polyunsaturated fatty acids.
AB  - BACKGROUND: Clinical chemistry and complete blood count (CBC) values were
      determined in 14 term baboons (Papio species) consuming formula with moderate or
      high levels of dietary long-chain polyunsaturated fatty acids (LCPUFA) from 2-12
      weeks of age. METHOD: Neonates were randomized to three groups: C: Control, no
      LCPUFA; L: 0.33% docosahexaenoic acid (DHA)/0.67% arachidonic acid (ARA) (w/w);
      L3:1.00% DHA/0.67% ARA (w/w). Blood chemistries were assessed at 6 and 12 weeks
      and CBC parameters were measured at 2, 4, 8, 10, 12 weeks of age. RESULTS:
      Dietary LCPUFA had significant effects on serum triglyceride (C > L,L3) and
      calcium (L > C,L3). No other significant effects of diet were detected; pooled
      values are presented for all other parameters. CONCLUSION: These data provide
      longitudinal biochemical and white cell/platelet/immunological data on LCPUFA-fed
      baboons over the first 12 weeks of life. Data ranges are similar to reference
      data in cases for which values exist and hematological changes reflect trends
      observed during human neonatal development.

PMID- 18333919
TI  - Voluntary consumption of substances of unknown palatability by vervet monkeys: a
      refinement.
AB  - BACKGROUND: Pure compounds and herbal medicines, had to be administered orally to
      vervet monkeys for testing. A reliable method was sought to avoid daily gavaging.
      METHODS: Substances were incorporated into the maize meal based diet of this
      facility for voluntary consumption. Food intake was monitored. RESULTS: In all
      but one case, consumption of the treated food was in excess of 90%. In all cases,
      the purpose of the study was achieved. Habituation was usually only required to
      the vehicle, and was accomplished by incremental increases to the desired
      concentration. Aversion was overcome by the addition of a small amount of honey.
      Plasma concentrations of a compound metabolite could be measured in one case
      after gavage and food consumption, and were similar for both methods. CONCLUSION:
      The method enables reliable voluntary consumption of diverse substances. Since
      stressful gavaging is avoided, it is a valuable contribution to the 3Rs.

PMID- 18333920
TI  - Establishment of an ELISA system for the determination of Japanese monkey
      calreticulin and its application to plasma samples in macaques.
AB  - BACKGROUND: Calreticulin (Crt) is a molecular chaperone in endoplasmic reticulum,
      assisting a correct folding of glycoproteins. Establishment of its assay method
      might be advantageous to determine the Crt level in cell or other biosystems.
      METHODS: An enzyme-linked immunosorbent assay (ELISA) system for the
      determination of Crt of Japanese monkey, Macaca fuscata, was developed in this
      study. Japanese monkey Crt protein expressed in Escherichia coli was used as a
      standard protein. RESULTS AND DISCUSSION: The assay was sensitive even to <10
      ng/ml of Crt. Since the amino acid sequence of Crt is quite similar (99%,
      similarity) between the Japanese and rhesus monkeys, the ELISA was applied to the
      determination of plasma Crt in these two species in association with various
      diseases. The Crt level increased significantly in monkeys suffering from
      pneumonia and diarrhea, suggesting that the ELISA might be applicable for
      preliminary diagnosis of inflammatory disease.

PMID- 18333921
TI  - Evaluation of the cardiovascular function of older adult Rhesus monkeys by
      ultrasonography.
AB  - OBJECTIVE: To evaluate the cardiovascular structure and function of older adult
      Rhesus monkey by utrasonography. METHODS: Sixteen monkeys aged from 17 to 20
      years and weighing from 8.2 to 15.3 kg, six adults aged 7-8 years and weighing
      from 8.1 to 9.2 kg. All monkeys were determined to be free from hypertension,
      hyperglycaemia and cardiac disease. The normal values of index related to heart
      and blood vessels including structure, haemodynamics and systolic or diastolic
      function were detected by 2D, M-mode, pulsed Doppler and tissue Doppler
      echocardiography respectively under ketamine hydrochloride sedation. Meanwhile,
      blood pressures were also measured by electronic sphygmomanometer. Each monkey
      underwent repeated detections in 2 weeks and all data were analysed with
      statistical methods. RESULTS: Compared with young adult monkeys, the older's
      heart rate (HR), the left ventricular diastolic function and the compliance of
      big artery including right and left common carotid artery, bulbus caroticus,
      internal carotid artery and abdominal aorta were decreased and the associated
      indexes changed significantly (P < 0.05 or P < 0.01). Meanwhile, older monkeys
      exhibited significant increase in the aorta diameter (AO), amplitude of aortic
      wall (AAO), left atrial diameter (LAD), end diastolic volume of left ventricle
      (EDV), stroke volume (SV), left ventricular mass (LVM) (P < 0.05 vs. young adult
      monkeys); however, cardiac output (CO) only slightly increased but the difference
      did not reach the statistical significance (P = 0.418, P = 0.644 respectively).
      CONCLUSIONS: The present results demonstrated the profiles of cardiovascular
      function and structure in the older Rhesus monkeys. Older monkey is accompanied
      by diminished left ventricular diastolic function and big artery compliance.
      Ultrasonography provides a means to non-invasively evaluate the anatomy and
      function of the heart and blood vessel, and plays an increasingly important role
      in the drug evaluation against cardiovascular dysfunction.

PMID- 18333922
TI  - Leadership and the use of evidence in practice.

PMID- 18333923
TI  - Figuring it out in the moment: a theory of unregulated care providers' knowledge
      utilization in dementia care settings.
AB  - BACKGROUND: Within the context of knowledge translation, the disconnect between
      the results of research and the practice patterns of nursing care providers has
      not been reported in the context of institutional dementia care practice.
      Therefore, little is known about how knowledge about best dementia care practice,
      defined broadly as the person-centered approach, gets used by institutional
      nursing care providers. AIM: Unregulated care providers provide the majority of
      nursing care for older people with Alzheimer's disease and related disorders
      living in long-term care facilities. The purpose of this grounded theory study
      was to explore the process whereby these workers use knowledge about person
      centered care in their dementia care practice. METHODS: Transcribed data from
      tape-recorded interviews with 20 unregulated care providers among eight long-term
      care facilities in Ontario, Canada, were coded and categorized at progressively
      more abstract levels until concepts and the relationships among them were
      integrated in a middle-range theory of knowledge utilization. RESULTS: The theory
      of Figuring it Out in the Moment illustrates how unregulated care providers in
      dementia care settings practice in the context of unpredictability, variability,
      and personal threat. Their use of knowledge about person-centered care is
      dependent on the existence of certain individual and relational conditions that
      interrelate with four separate, but interconnected, phases of clinical decision
      making and action. CONCLUSIONS: As a middle-range theory, Figuring it Out in the
      Moment is concrete and pragmatic information for promoting evidence-based
      dementia care not included in existing overarching knowledge utilization
      frameworks. Areas for further investigation include how knowledge utilization is
      conceptualized, as well as the influences of practitioners' clinical decision
      making, the nature of caregiving with particular client populations, and the
      characteristics of individuals alone and in relationship on the utilization of
      best practice knowledge.

PMID- 18333924
TI  - Translating best practices in assessing capillary refill.
AB  - PURPOSE: A research roundtable was held in an urban community hospital in the
      United States to determine the strength, usefulness, and feasibility of empirical
      and clinical evidence evaluated in a systematic review assessing capillary
      refill. APPROACH: The roundtable was undertaken to provide an additional
      dimension for the development of a best-practice guideline. Current practices and
      policies in this acute care hospital were examined concerning the strength of the
      evidence. CONCLUSIONS AND RECOMMENDATIONS: Isolated performance of capillary
      refill assessment is of limited value and no nursing interventions rely solely on
      this measure. Future research should be directed toward evaluation and
      comparative analyses of alternate methods of evaluating peripheral perfusion.

PMID- 18333925
TI  - How systematic reviews can foster evidence-based clinical decisions.

PMID- 18333928
TI  - Editorial: a global perspective on child and adolescent mental health.

PMID- 18333930
TI  - Multicultural assessment of child and adolescent psychopathology with ASEBA and
      SDQ instruments: research findings, applications, and future directions.
AB  - Around the world, cultural blending and conflict pose challenges for assessment
      and understanding of psychopathology. Economical, evidence-based, culturally
      robust assessment is needed for research, for answering public health questions,
      and for evaluating immigrant, refugee, and minority children. This article
      applies multicultural perspectives to behavioral, emotional, and social problems
      assessed on dimensions describing children's functioning, as rated by parents,
      teachers, children, and others. The development of Achenbach System of
      Empirically Based Assessment (ASEBA) and Strengths and Difficulties Questionnaire
      (SDQ) forms and their applications to multicultural research are presented. A
      primary aim of both questionnaires is to identify children at high risk of
      psychiatric disorders and who therefore warrant further assessment. The forms are
      self-administered or administered by lay interviewers. ASEBA problem items are
      scored on 6 DSM-oriented scales and 3 broader band scales, plus 8 syndromes
      derived statistically as taxonomic constructs and supported by uniform
      confirmatory factor analyses of samples from many populations. Comparisons of
      ASEBA scale scores, psychometrics, and correlates are available for diverse
      populations. SDQ forms are scored on one broad-band scale and 5 a priori
      behavioral dimensions supported by data from various populations. For both
      instruments, factor analyses, psychometrics, and correlates are available for
      diverse populations. The willingness and ability of hundreds of thousands of
      respondents from diverse groups to complete ASEBA and SDQ forms support this
      approach to multicultural assessment. Although particular items and scales may
      have differential relevance among groups and additional assessment procedures are
      needed, comparable results are found in many populations. Scale scores vary more
      within than between populations, and distributions of scores overlap greatly
      among different populations. Ratings of children's problems thus indicate more
      heterogeneity within populations than distinctiveness between populations. Norms
      from multiple populations can be used to compare children's scores with relevant
      peer groups. Multicultural dimensional research can advance knowledge by
      diversifying normative data; by comparing immigrant children with nonimmigrant
      compatriots and with host country children; by identifying outlier findings for
      elucidation by emic research; and by fostering efforts to dimensionalize DSM-V
      diagnostic criteria.

PMID- 18333929
TI  - Psychiatric diagnosis - is it universal or relative to culture?
AB  - BACKGROUND: There is little consensus on the extent to which psychiatric
      disorders or syndromes are universal or the extent to which they differ on their
      core definitions and constellation of symptoms as a result of cultural or
      contextual factors. This controversy continues due to the lack of biological
      markers, imprecise measurement and the lack of a gold standard for validating
      most psychiatric conditions. METHOD: Empirical studies were used to present
      evidence in favor of or against a universalist or relativistic view of child
      psychiatric disorders using a model developed by Robins and Guze to determine the
      validity of psychiatric disorders. RESULTS: The prevalence of some of the most
      common specific disorders and syndromes as well as its risk and protective
      factors vary across cultures, yet comorbid patterns and response to treatments
      vary little across cultures. Cross-cultural longitudinal data on outcomes is
      equivocal. CONCLUSIONS: The cross-cultural validity of child disorders may vary
      drastically depending on the disorder, but empirical evidence that attests for
      the cross-cultural validity of diagnostic criteria for each child disorder is
      lacking. There is a need for studies that investigate the extent to which gene
      environment interactions are related to specific disorders across cultures.
      Clinicians are urged to consider culture and context in determining the way in
      which children's psychopathology may be manifested independent of their views.
      Recommendations for the upcoming classificatory system are provided so that
      practical or theoretical considerations are addressed about how culture and
      ethnic issues affect the assessment or treatment of specific disorders in
      children.

PMID- 18333931
TI  - Diffusion of efficacious interventions for children and adolescents with mental
      health problems.
AB  - BACKGROUND: Child and adolescent mental health problems are prevalent and require
      adequate interventions. Despite several evidence-based interventions for these
      problems described in the literature, few studies addressed strategies to diffuse
      efficacious interventions for child mental disorders especially in developing
      countries. METHODS: An extensive but not systematic review of the literature was
      performed aiming to identify evidence-based interventions for children and
      adolescents with mental disorders, professionals to target in disseminating these
      interventions, and the available strategies to diffuse information. RESULTS:
      Substantial evidence-based information is available to guide preventive,
      psychosocial and psychopharmacological interventions. The effectiveness of
      treatments in real-world settings and the cost-effectiveness of interventions are
      rarely tested. Professionals at different levels (teachers, school counselors,
      social workers, general practitioners, pediatricians, child psychologists and
      psychiatrists) should be targeted in diffusing efficacious interventions for
      child mental health problems worldwide. Telepsychiatry and the internet seem to
      be the most promising strategies to diffuse knowledge with lower costs.
      CONCLUSIONS: Medical and allied professionals must incorporate child and
      adolescent mental health issues in their under- and postgraduate curricula, and
      be better prepared to critically evaluate available information. Professionals
      need to disseminate evidence-based programs to guide parents and teachers in
      developing countries to deal with child and adolescent difficulties. Countries
      need to explore internet solutions for dissemination of medical information.

PMID- 18333933
TI  - Protecting confidentiality in maternal mortality enquiries--getting the balance
      right?

PMID- 18333934
TI  - Translational research in gynaecological oncology.

PMID- 18333935
TI  - Costing magnetic resonance-guided focused ultrasound surgery, a new treatment for
      symptomatic fibroids.

PMID- 18333936
TI  - An estimation of intrapartum-related perinatal mortality rates for booked home
      births in England and Wales between 1994 and 2003.
AB  - OBJECTIVE: The objective of this study was to obtain the best estimate of
      intrapartum-related perinatal mortality (IPPM) rates for booked home births.
      DESIGN: A population-based cross-sectional study. SETTING: England and Wales.
      SUBJECTS: All births in England and Wales, including home births (intended or
      unintended) occurring between 1994 and 2003. METHODS: All IPPM data were derived
      from the Confidential Enquiry into Maternal and Child Health. Denominators were
      derived by using unintended home births and transfer rates from home to hospital,
      from previous studies, with sensitivity analyses. IPPM rates were calculated for
      the three following subgroups: (a) the completed home birth group, (b) the
      transferred group and (c) the unintended home birth group. OUTCOME: IPPM rate.
      RESULTS: The overall IPPM rate for England and Wales improved between 1994 and
      2003. However, data to obtain a precise estimate of IPPM rate for booked home
      birth were not available. The average IPPM rate for all births in the study
      period was 0.79 per 1000 births (95% CI 0.77-0.81), and the estimated IPPM rate
      for booked home births was 1.28 or 0.74 per 1000 births, depending on the method
      of calculation (range 0.49-1.47). The IPPM rates for the completed home birth
      group appeared to be lower throughout the study period compared with the
      unintended home birth groups. Those women who had booked for a home birth, but
      later needed to transfer their care for a hospital birth, appeared to have the
      highest risk of IPPM in the study period. CONCLUSIONS: The results of this study
      need to be interpreted with caution due to inconsistencies occurring in the
      recorded data. However, the data do highlight two important features. First, they
      suggest that IPPM rates for home births do not appear to have improved over the
      study period examined, even though rates did so overall. Second, although the
      women who booked for home births and had their babies at home seemed to have a
      generally low IPPM rate, those who required their care to be transferred to
      hospital did not. Women who book for home births should be offered comprehensive
      evidence-based information about the potential benefits, risks and uncertainties
      associated with their choice of birthplace by the healthcare professional
      responsible for supporting their decision. It is of considerable concern that the
      data recorded nationally in England and Wales do not provide accurate information
      about when and why a transfer from home to hospital booking occurs and about
      their outcomes.

PMID- 18333937
TI  - Oxytocin-ergometrine co-administration does not reduce blood loss at caesarean
      delivery for labour arrest.
AB  - OBJECTIVE: To determine if intravenous infusion of a combination of oxytocin and
      ergometrine maleate is better than oxytocin alone to decrease blood loss at
      caesarean delivery for labour arrest. DESIGN: Prospective, double-blinded,
      randomised controlled trial. SETTING: Mount Sinai Hospital, Toronto, Canada.
      POPULATION: Women undergoing caesarean deliveries for labour arrest. METHODS:
      Forty-eight women were randomised to receive infusion of either ergometrine
      maleate 0.25 mg + oxytocin 20 iu or oxytocin 20 iu alone, diluted in 1 l of
      lactated Ringer's Solution, immediately after delivery of the infant.
      Unsatisfactory uterine contractions after delivery were treated with additional
      boluses of the study solution or rescue carboprost. Blood loss was estimated
      based on the haematocrit values before and 48 hours after delivery. MAIN OUTCOME
      MEASURES: The primary outcome was the estimated blood loss, while the secondary
      outcomes included the use of additional uterotonics, need for blood transfusion
      and the incidence of adverse effects. RESULTS: The estimated blood loss was
      similar in the oxytocin-ergometrine and oxytocin-only groups; 1218 +/- 716 ml and
      1299 +/- 774 ml, respectively (P = 0.72). Significantly fewer women required
      additional boluses of the study drug in the oxytocin-ergometrine group (21 and
      57%; P = 0.01). Nausea (42 and 9%; P = 0.01) and vomiting (25 and 4%; P = 0.05)
      were significantly more prevalent in the oxytocin-ergometrine group. CONCLUSIONS:
      In women undergoing caesarean delivery for labour arrest, the co-administration
      of ergometrine with oxytocin does not reduce intraoperative blood loss, despite
      apparently superior uterine contraction.

PMID- 18333938
TI  - Expected day of delivery from ultrasound dating versus last menstrual period-
      obstetric outcome when dates mismatch.
AB  - OBJECTIVE: To analyse the association between fetal size at time of dating
      ultrasound and risk for preterm delivery and small-for-gestational-age (SGA)
      birth and to evaluate if timing of ultrasound, that is before 14 weeks of
      gestation or after 16 weeks affects this association. DESIGN: Retrospective
      cohort study. SETTING: Ultrasound departments of Ultragyn, Stockholm, Sweden.
      POPULATION: A total of 28,776 singleton pregnancies dated between 1998 and 2004.
      METHODS: Obstetric outcome was assessed through linkage of the cohort to the
      Swedish Medical Birth Register. MAIN OUTCOME MEASURES: Risks of preterm delivery,
      low birthweight for gestational age, pre-eclampsia, asphyxia, respiratory
      distress, instrumental delivery, caesarean section, and postterm birth were
      calculated for the groups dated early and late. RESULTS: When the expected date
      of delivery was postponed after ultrasound dating by 7 days or more, there was an
      increased risk for preterm delivery and pre-eclampsia in the late dating group
      (OR 1.49, 95% CI 1.27-1.73 and OR 1.27, 95% CI 1.02-1.60, respectively) but not
      in the early dating group. In both dating groups, there was an increased risk for
      SGA birth (OR 1.77, 95% CI 1.13-2.78 and OR 2.09, 95% CI 1.59-2.73, respectively)
      There was no increased risk for any of the other diagnoses. CONCLUSION: Our study
      gives further support to the notion that intrauterine growth restriction may be
      present as early as the first trimester. Accordingly, our study also suggests
      that surveillance of pregnancies with postponed estimated date of delivery may
      provide means for increased detection of fetal growth restriction.

PMID- 18333939
TI  - Predictiveness of antenatal umbilical artery Doppler for adverse pregnancy
      outcome in small-for-gestational-age babies according to customised birthweight
      centiles: population-based study.
AB  - OBJECTIVE: To examine the relationship between smallness at birth and the
      predictive value of umbilical artery Doppler. DESIGN: Retrospective cohort.
      SETTING: Tertiary referral university hospital, Barcelona. POPULATION: A total of
      7645 singleton pregnancies delivered between January 2002 and June 2004. METHODS:
      The associations with adverse outcome were assessed for small-for-gestational-age
      (SGA) babies according to customised standards who had normal and abnormal
      umbilical artery Doppler. MAIN OUTCOME MEASURES: Neonatal morbidity and perinatal
      mortality. RESULTS: Of the 369 SGA fetuses that had been identified antenatally,
      70 (19%) had an abnormal umbilical artery Doppler and the babies from these
      pregnancies had a higher risk for neonatal morbidity when compared with babies
      with normal birthweight (OR 3.99, 95% CI 1.04-11.03). However, the remaining 299
      (81%) fetuses with normal umbilical artery Doppler also had an elevated risk of
      neonatal morbidity (OR 2.26, 95% CI 1.04-4.39). Overall, many of the instances of
      adverse outcome associated with smallness for gestational age were attributable
      to the group with normal Doppler than to the group with abnormal Doppler.
      CONCLUSION: Normal antenatal umbilical artery Doppler cannot be taken as an
      indicator of low risk in pregnancies where the fetus is SGA according to
      customised percentiles.

PMID- 18333940
TI  - Outcome of anaemic monochorionic single survivors following early intrauterine
      rescue transfusion in cases of feto-fetal transfusion syndrome.
AB  - OBJECTIVE: To evaluate the outcome of severely anaemic monochorionic (MC) twins
      surviving the death of their co-twin following early intrauterine rescue
      transfusion in cases of feto-fetal transfusion syndrome (FFTS). STUDY DESIGN: We
      reviewed all MC pregnancies complicated with FFTS following primary management,
      in which a single intrauterine fetal death (IUFD) was diagnosed with certainty
      within 24 hours between January 1999 and December 2006. We included MC survivors
      who presented ultrasound or Doppler features of fetal anaemia following the death
      of their co-twin. Intrauterine transfusion (IUT) was given to all survivors who
      were anaemic. RESULTS: Nineteen MC twin pregnancies presented a single
      intrauterine death (IUD) associated with an anaemic co-twin. Median gestational
      age at IUD was 23 [20-28] weeks. The median interval between IUD and IUT was 12
      [8-24] hours. There were 58% (11/19) healthy survivors. Perinatal death rate was
      26% (5/19) including 16% (3/19) intrauterine and 10% (2/19) neonatal deaths.
      Abnormal prenatal cerebral findings developed in 21% (4/19) cases, always within
      1 month after the death of the co-twin. Considering occlusive techniques and
      other management separately, there were 64% (7/11) and 50% (4/8) healthy
      survivors, respectively, and perinatal death occurred in 36% (4/11) and 12.5%
      (1/8) of fetuses, respectively. Prenatal fetal cerebral lesions developed in 9%
      (1/11) of cases following occlusive techniques and in 37.5% (3/8) of fetuses when
      managed differently. The median gestational age at delivery in the survivors was
      31 [25-38] weeks. CONCLUSION: In cases of FFTS with single anaemic survivors,
      early IUT could be offered following extensive counselling and close follow up.

PMID- 18333941
TI  - Establishment of reference range for thyroid hormones in normal pregnant Indian
      women.
AB  - BACKGROUND: Interpretation of thyroid function tests during pregnancy needs
      trimester-related reference intervals from pregnant populations with minimal risk
      for thyroid dysfunction. While India has become iodine sufficient after two
      decades of salt iodisation, there is no normative data for thyroid function from
      healthy pregnant women of this country. AIMS AND OBJECTIVES: To determine
      trimester-specific reference ranges for free triiodothyronine (FT(3)), free
      thyroxine (FT(4)) and thyrotropin (TSH) from healthy pregnant Indian women.
      DESIGN: Cross-sectional study in a reference population of pregnant women.
      SETTING: Primary care level obstetric department in India. POPULATION: Women with
      uncomplicated pregnancy in any trimester. METHODS: Five hundred and forty-one
      apparently healthy pregnant women with uncomplicated single intrauterine
      gestations reporting to the Armed Forces Clinic in any trimester were
      consecutively recruited. Clinical examination, thyroid ultrasound for
      echogenicity and nodularity and estimation of FT(3), FT(4), TSH and antithyroid
      antibodies (antithyroperoxidase [anti-TPO] and antithyroglobulin [anti-Tg]) using
      electrochemiluminescence technique were carried out. From this entire sample, a
      disease- and risk-free reference population was obtained by excluding those with
      any known factor that could affect thyroid function or those who were being
      treated for thyroid dysfunction. MAIN OUTCOME MEASURE: None. RESULTS: Of the 541
      consecutive pregnant women in different trimesters enrolled for the study, 210
      women were excluded. The composition of reference population comprising 331 women
      was 107 in first trimester, 137 in second trimester and 87 in third trimester.
      The 5th and 95th percentiles values were used to determine the reference ranges
      for FT(3), FT(4) and TSH. The trimester-wise values in the first, second and
      third trimesters were: FT(3) (1.92-5.86, 3.2-5.73 and 3.3-5.18 pM/l), FT(4) (12
      19.45, 9.48-19.58 and 11.32-17.7 pM/l) and TSH (0.6-5.0, 0.44-5.78 and 0.74-5.7
      iu/ml), respectively. Analysis of mean, median values for FT(3), FT(4) and TSH
      between each trimester showed no significant difference in FT(3) and TSH values
      (95% CI). However, FT(4) showed significant variation between trimesters with
      values decreasing with advancing gestational age (P value: first versus second =
      0.015, first versus third = 0.003 and second versus third = not significant).
      Women with antibody positivity and hypoechogenicity of thyroid gland had
      significantly higher TSH values when compared with women with antibody negativity
      and normoechogenicity. CONCLUSIONS: Reference ranges of FT(3), FT(4) and TSH have
      been established for pregnant Indian women using 5th and 95th percentiles.

PMID- 18333942
TI  - Is psychosocial stress in first ongoing pregnancies associated with pre-eclampsia
      and gestational hypertension?
AB  - OBJECTIVE: Investigating the association of pre-eclampsia and gestational
      hypertension with psychosocial stress in the first half of pregnancy. DESIGN:
      Prospective community-based cohort study. SETTING: Amsterdam, The Netherlands.
      POPULATION: Between January 2003 and March 2004, all pregnant Amsterdam women (n
      = 12 377) were invited to fill in a questionnaire with sociodemographic and
      psychosocial variables (response rate 67%). Only nulliparous women with a
      singleton pregnancy, who completed the questionnaire before 24 weeks, and
      delivered after 24 weeks, were included. METHODS: A postpartum questionnaire was
      used to gather information on hypertension or proteinuria. If this questionnaire
      was not available, the national obstetric register was used for pregnancy
      outcome. Medical files were examined for women with hypertension and/or
      proteinuria to confirm the diagnosis of pre-eclampsia and gestational
      hypertension according to the International Society for the Study of Hypertension
      in Pregnancy guidelines. Psychosocial stress was defined as workstress (Work
      Experience and Appreciation Questionnaire partly based on the Job Content
      Instrument of Karasek et al.), anxiety (the State-Trait Anxiety Inventory),
      depression (Center for Epidemiological Studies Depression Scale) and pregnancy
      related anxiety (PRAQ-R). The association of psychosocial stress with the
      incidence of pre-eclampsia and gestational hypertension was explored by
      multivariate analysis adjusted for sociodemographic and medical confounders. MAIN
      OUTCOME MEASURES: Incidence of pre-eclampsia and gestational hypertension.
      RESULTS: A total of 3679 women were included. The incidence of pre-eclampsia and
      gestational hypertension was 3.5 and 4.4%, respectively. Workstress, anxiety,
      pregnancy-related anxiety or depression had no effect on the incidence of pre
      eclampsia or gestational hypertension. CONCLUSION: Psychosocial stress in the
      first half of pregnancy does not influence the incidence of pre-eclampsia and
      gestational hypertension in nulliparous women.

PMID- 18333943
TI  - Maternal HIV status and pregnancy outcomes in northeastern Tanzania: a registry
      based study.
AB  - OBJECTIVES: The proportion of women delivering with known HIV status in sub
      Saharan Africa is not well described. Risk of HIV transmission to newborns is a
      major concern, but there may also be increased risks for other adverse pregnancy
      outcomes. DESIGN: Hospital registry. SETTING: North East Tanzania (1999-2006).
      POPULATION: Singletons (n = 14,444). METHODS: Births were grouped by maternal HIV
      status and socio-demographic factors predicting HIV status, and associations
      between status and pregnancy outcomes were studied. MAIN OUTCOME MEASURES:
      Maternal HIV status, perinatal mortality, prematurity, small for gestational age
      (SGA), birthweight and low Apgar score. RESULTS: The proportion of mothers with
      known HIV status increased from 7% before 2001 to 78% after 2004. Single
      motherhood, rural residence, low maternal education, maternal and paternal
      farming and higher paternal age were associated with unknown HIV status. About
      7.4% (95% CI 6.7-8.1%) of women were HIV infected, with increased likelihood of
      infection with higher gravidity, single motherhood, rural residence, maternal
      business or farming occupations and paternal tribe. Compared with HIV-uninfected
      women, the untreated HIV-infected women had a higher risk of SGA births (adjusted
      risk ratio [ARR] 1.6; 95% CI 1.1-2.4), preterm birth (ARR 1.8; 95% CI 1.1-2.7)
      and perinatal death (ARR 1.9; 95% CI 0.95-3.8). Women with unknown HIV status had
      moderately increased risks. Treated HIV-infected women had a risk similar to that
      of the HIV-uninfected women for all outcomes, except for low Apgar score.
      CONCLUSION: HIV testing and infection were associated with socio-demographic
      factors. Untreated HIV-infected women had higher risks of adverse pregnancy
      outcomes, and risks were also increased for women with unknown HIV status. There
      is still a need to increase availability of HIV testing, education and adequate
      therapy for pregnant women.

PMID- 18333944
TI  - Gender differences in final year medical students' experience of teaching of
      intimate examinations: a questionnaire study.
AB  - OBJECTIVES: To examine final year medical students' experience of being taught to
      conduct intimate examinations. DESIGN: Prospective questionnaire study. SETTING:
      Medical school in the UK. POPULATION: Medical students in the final year cohort
      2005/06. METHODS: Questionnaires were distributed to students in the final week
      of a final year obstetrics and gynaecology course. Responses to questions about
      course experience were analysed using frequencies and single-variable analyses.
      MAIN OUTCOME MEASURES: Students' experience of and satisfaction with the teaching
      of intimate examinations and differences between male and female students.
      RESULTS: Male and female students performed similar numbers of intimate
      examinations, but clinical tutors were significantly more likely to introduce
      female students to patients (76 versus 52%; P = 0.001) and obtain consent on
      their behalf (75 versus 53%; P = 0.009) when compared with male students. Male
      students reported a greater degree of embarrassment (mean score 2.41 +/- 1.25
      versus 1.69 +/- 0.90; P = 0.002), and a higher number of patients refusing
      consent to examination (median 2; range 0-12 versus 0; range 0-6; P = 0.0001).
      CONCLUSIONS: Gender discrimination in the behaviour of tutors may impact on
      students' experience of intimate examinations. It is highly improbable that
      differences in behaviour are deliberately intended to disadvantage male students,
      and further research is needed to understand why tutors behave differently with
      them. In the meantime, tutors need to be aware of potential bias and ensure
      appropriate support is provided for both male and female students.

PMID- 18333945
TI  - Genetic variants of interleukin-1RN and interleukin-1beta genes and risk of
      cervical cancer.
AB  - OBJECTIVES: Inflammation plays a major role in pathogenesis of cervical cancer.
      We planned to study whether polymorphisms in inflammation-related genes, IL-1RN
      (VNTR) and IL-1beta (-511C/T), are associated with risk of cervical cancer.
      DESIGN: Case-control study. SETTING: Uttar Pradesh state in India. SAMPLE: One
      hundred and fifty, histopathologically confirmed cases with cervical cancer and
      162 age-, ethnicity-matched, cervical cytology negative, healthy controls were
      recruited to this study. METHODS: Genotyping of IL-1RN (VNTR) and IL-1beta (
      511C/T) polymorphisms was performed using polymerase chain reaction (PCR)/PCR
      restriction fragment length polymorphism. Power of study was 80% with type 1
      error of 0.05. Haplotypes frequencies were obtained by computer package
      'Arlequin'. MAIN OUTCOME MEASURES: Haplotype IL-1RN*2/IL-1beta*T is associated
      with higher risk and of cervical cancer. RESULTS: IL-1RN genotypes 1/2 and 2/2
      were associated with significantly elevated risk of cervical cancer (OR = 3.3; P=
      4.9 x 10(-6) and OR = 2.9, P= 0.02). Similarly, TT genotype of IL
      1betapolymorphism was significantly higher in cases compared with controls (57.7
      versus 38.3%; OR = 2.8; P = 0.012). 2/2 genotype of IL-1RN (OR = 4.8, P = 0.0006)
      and TT genotype of IL-1beta(OR = 5.2; P = 0.02) were associated with the higher
      stages (III) of cervical cancer. Haplotypes 1T (IL-1RN*1/IL-1beta*T) and 2T (IL
      1RN*2/IL-1beta*T) were also significantly associated with higher susceptibility
      to cervical cancer and its progression. Logistic regression analysis suggests IL
      1RN allele 2 and IL-1beta-511T were independently associated with increased risk
      for cervical cancer. CONCLUSION: IL-1RN*2 and IL-1beta -511*T in various
      combinations of genotypes and haplotypes are associated with higher
      susceptibility for cervical cancer.

PMID- 18333946
TI  - pH-balanced tampons: do they effectively control vaginal pH?
AB  - OBJECTIVE: To determine if tampons lubricated with pH-balanced gel are effective
      at maintaining normal vaginal pH. DESIGN: Randomised controlled trial. SETTING:
      Urban family planning clinic and teaching hospital. POPULATION: Healthy
      volunteers using the combined oral contraceptive pill. METHODS: Women were
      randomised to use an existing lubricating gel (pH 5.1) or a lactic acid-buffered
      gel (pH 3.8-4.2) with regular size, non-applicator tampons. In the preceding
      control cycle, women used identical tampons without gel. MAIN OUTCOME MEASURES:
      Vaginal pH < or = 4.5, microbiology (candida and bacterial vaginosis [BV]) and
      colposcopic appearance within 72 hours of tampon use, subject acceptability and
      symptoms. RESULTS: Eighty-one out of 98 (83%) women completed the study. No
      significant difference was observed between tampons with the standard gel
      formulation, the pH-balanced gel and nonlubricated tampons in terms of vaginal
      pH, microbiological evidence of candida or BV, or colposcopic appearance.
      Acceptability scores were significantly higher for lubricated tampons compared
      with nonlubricated tampons (P < 0.05), although there was no difference in
      reported symptoms. CONCLUSIONS: Tampons lubricated with pH-balanced gel do not
      control vaginal pH. There was no evidence of measurable health benefits of
      lubricated tampons, but women preferred tampons with [corrected] lubrication.

PMID- 18333947
TI  - Anaesthetic choice in the colposcopy clinic: a retrospective analysis of
      routinely collected data.
AB  - OBJECTIVES: Current guidelines recommend that less than 20% of treatments in
      colposcopy clinics should be under general anaesthetic. The objective of this
      study was to increase the evidence base for guidelines by establishing the
      proportion of women receiving general anaesthesia for treatment, determining the
      predictors of and reasons recorded for general anaesthetic use. DESIGN:
      Retrospective analysis of routinely collected data. SETTING: NHS Trust in the
      West Midlands. PARTICIPANTS: Colposcopy patients; January 2003 to March 2005.
      METHODS: Logistic regression of factors associated with general anaesthetic
      choice. MAIN OUTCOME MEASURES: Proportion of women treated under general
      anaesthesia, factors associated with anaesthetic choice and reasons recorded for
      general anaesthetic use. RESULTS: About 5.4% (204/3777) of new appointments for
      colposcopy received treatment under general anaesthetic. Of women requiring
      treatment, 20% (204/1003) received general anaesthetic. General anaesthetic was
      more likely to be used when the woman required loop excision (OR = 3.63, 95% CI
      2.11-6.24) and less likely when directed biopsy was performed (OR = 0.11, 95% CI
      0.01-0.80), when the patient appointment date was after introduction of new
      guidelines (OR = 0.37, 95% CI 0.24-0.56) or when the assessment visit was with a
      nonconsultant status doctor rather than nurse or consultant (OR = 0.70, 95% CI
      0.50-0.97). General anaesthetic use varied between colposcopists ranging from 0
      to 16.5% of new patients seen. Woman's choice was the most commonly specified
      reason for the use of general anaesthetic. CONCLUSIONS: The proportion of
      colposcopy patients treated under general anaesthetic is 20%, within guideline
      limits. Substantial variation in general anaesthetic rates between colposcopists
      was observed, and further investigation is required to discover the reason for
      this.

PMID- 18333949
TI  - The contribution of late termination of pregnancy to stillbirth rates in Northern
      England, 1994-2005.
AB  - The impact of late terminations (> or = 24 weeks) on the overall stillbirth rate
      was determined for the 12-year period from 1994 to 2005 using data collected by
      the Regional Maternity Survey Office in the north of England. It is a legal
      requirement to register late terminations, and this may lead to an overestimation
      of the true stillbirth rate. In our region, terminations resulting in stillbirth
      increased the registered stillbirth rate by nearly 10%. The impact remained
      stable for the period 1998-2005. This suggests that the failure of the national
      (and regional) stillbirth rate to decline in recent years is not due to an
      increase in late terminations.

PMID- 18333948
TI  - Cost-effectiveness of magnetic resonance-guided focused ultrasound surgery for
      treatment of uterine fibroids.
AB  - OBJECTIVE: To estimate the cost-effectiveness of a treatment strategy for
      symptomatic uterine fibroids, which starts with Magnetic Resonance-guided Focused
      Ultrasound Surgery (MRgFUS) as compared with current practice comprising uterine
      artery embolisation, myomectomy and hysterectomy. DESIGN: Cost-utility analysis
      based on a Markov model. SETTING: National Health Service (NHS) Trusts in England
      and Wales. POPULATION: Women for whom surgical treatment for uterine fibroids is
      being considered. METHODS: The parameters of the Markov model of the treatment of
      uterine fibroids are drawn from a series of clinical studies of MRgFUS, and from
      the clinical effectiveness literature. Health-related quality of life is measured
      using the 6D. Costs are estimated from the perspective of the NHS. The impact of
      uncertainty is examined using deterministic and probabilistic sensitivity
      analysis. MAIN OUTCOME MEASURES: Incremental cost-effectiveness measured by cost
      per quality-adjusted life-year (QALY) gained. RESULTS: The base-case results
      imply a cost saving and a small QALY gain per woman as a result of an MRgFUS
      treatment strategy. The cost per QALY gained is sensitive to cost of MRgFUS
      relative to other treatments, the age of the woman and the nonperfused volume
      relative to the total fibroids volume. CONCLUSIONS: A treatment strategy for
      symptomatic uterine fibroids starting with MRgFUS is likely to be cost-effective.

PMID- 18333950
TI  - Centralisation of services for the management of ovarian cancer.

PMID- 18333952
TI  - Limitations of ST analysis in clinical practice: three cases of intrapartum
      metabolic acidosis.

PMID- 18333954
TI  - Limitations of ST analysis in clinical practice: three cases of intrapartum
      metabolic acidosis.

PMID- 18333957
TI  - Short-term plasticity of central benzodiazepine receptors in status epilepticus:
      case report.
AB  - (123)I-iomazenil SPECT is of value in determining an epileptogenic focus,
      however, transient uptake change has been rarely reported in epileptic disorders.
      A 78-year-old woman diagnosed as status epilepticus (SE) showed transient
      reduction in (123)I-iomazenil uptake within the epileptic foci on SPECT images
      during a couple of weeks. It suggests a seizure-related 'short-term' plasticity
      in the central benzodiazepine receptors and dynamic change in the regulatory
      mechanisms of inhibitory neurotransmitter system within the epileptic foci in
      patients with SE.

PMID- 18333958
TI  - An insufficient effect of lamotrigine leading to fatal seizures.

PMID- 18333960
TI  - Doublecortin as a marker of adult neuroplasticity in the canary song control
      nucleus HVC.
AB  - It is established that in songbirds the size of several brain song control nuclei
      varies seasonally, based on changes in cell size, dendritic branching and, in
      nucleus HVC, the incorporation of newborn neurons. In the developing and adult
      mammalian brain, the protein doublecortin (DCX) is expressed in postmitotic
      neurons and, as a part of the microtubule machinery, required for neuronal
      migration. We recently showed that in adult canaries, DCX-immunoreactive (ir)
      cells are present throughout the telencephalon, but the link between DCX and the
      active neurogenesis observed in songbirds remained uncertain. We demonstrate here
      that DCX labels recently born cells in the canary telencephalon and that, in
      parallel with changes in HVC volume, the number of DCX-ir cells is increased
      specifically in the HVC of testosterone-treated males compared with castrates,
      and in castrated testosterone-treated males paired with a female as compared with
      males paired with another male. The numbers of elongated DCX-ir cells
      (presumptive migrating neurons) and round multipolar DCX-ir cells
      (differentiating neurons) were also affected by the sex of the subjects and their
      photoperiodic condition (photosensitive vs photostimulated vs photorefractory).
      Thus, in canaries the endocrine state, as well as the social or photoperiodic
      condition independently of variation in steroid hormone action, affects the
      number of cells expressing a protein involved in neuronal migration specifically
      in brain areas that incorporate new neurons in the telencephalon. The DCX gene
      may be one of the targets by which testosterone and social stimuli induce
      seasonal changes in the volume of song nuclei.

PMID- 18333959
TI  - Impact of sex and hormones on new cells in the developing rat hippocampus: a
      novel source of sex dimorphism?
AB  - The hippocampus is a key brain region regulating complex cognitive and emotional
      responses, and is implicated in the etiology of depressive and anxiety disorders,
      many of which exhibit some degree of sex difference. The male rat hippocampus is
      consistently reported to be slightly but significantly larger than the female.
      The majority of studies on the development of volumetric sex differences have
      focused on the effects of estradiol (E2), with relatively few focusing on
      androgens. We examined the impact of both E2 and androgens on newly born cells in
      the developing rat hippocampus, and report that neonatal males have significantly
      more 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdU)+ cells than females. Both
      testosterone (T) and dihydrotestosterone treatment of females significantly
      increased the number of BrdU+ cells, an effect blocked by the androgen receptor
      antagonist, flutamide. However, only T significantly increased the number of
      neuronal nuclear antigen+ neurons in the female rat hippocampus. Interestingly,
      E2 treatment also increased BrdU+ cells in females, but had no effect on neuron
      number. Instead, E2 and T significantly increased the number of newly born glial
      fibrillary acidic protein or glutamine synthetase+ glial cells in females,
      indicating that androgens and E2 may act independently to achieve distinct
      endpoints. Quantification of pyknotic cells at two different developmental time
      points indicates no sex difference in the number of cells dying, suggesting, but
      not proving, that gonadal steroids are promoting cell genesis.

PMID- 18333961
TI  - CXCR4 receptors in the dorsal medulla: implications for autonomic dysfunction.
AB  - The chemokine receptor, CXCR4, plays an essential role in guiding neural
      development of the CNS. Its natural agonist, CXCL12 [or stromal cell-derived
      factor-1 (SDF-1)], normally is derived from stromal cells, but is also produced
      by damaged and virus-infected neurons and glia. Pathologically, this receptor is
      critical to the proliferation of the HIV virus and initiation of metastatic cell
      growth in the brain. Anorexia, nausea and failed autonomic regulation of
      gastrointestinal (GI) function cause morbidity and contribute to the mortality
      associated with these disease states. Our previous work on the peripheral
      cytokine, tumor necrosis factor-alpha, demonstrated that similar morbidity
      factors involving GI dysfunction are attributable to agonist action on neural
      circuit elements of the dorsal vagal complex (DVC) of the hindbrain. The DVC
      includes vagal afferent terminations in the solitary nucleus, neurons in the
      solitary nucleus (NST) and area postrema, and visceral efferent motor neurons in
      the dorsal motor nucleus (DMN) that are responsible for the neural regulation of
      digestive functions from the oral cavity to the transverse colon.
      Immunohistochemical techniques demonstrate a dense concentration of CXCR4
      receptors on neurons throughout the DVC and the hypoglossal nucleus. CXCR4
      immunoreactivity is also intense on microglia within the DVC, though not on the
      astrocytes. Physiological studies show that nanoinjection of SDF-1 into the DVC
      produces a significant reduction in gastric motility in parallel with an
      elevation in the numbers of cFOS-activated neurons in the NST and DMN. These
      results suggest that this chemokine receptor may contribute to autonomically
      mediated pathophysiological events associated with CNS metastasis and infection.

PMID- 18333962
TI  - SATB2 interacts with chromatin-remodeling molecules in differentiating cortical
      neurons.
AB  - During our search for developmental regulators of neuronal differentiation, we
      identified special AT-rich sequence-binding protein (SATB)2 that is specifically
      expressed in the developing rat neocortex and binds to AT-rich DNA elements. Here
      we investigated whether the regulatory function of SATB2 involves chromatin
      remodeling at the AT-rich DNA site. In-vitro and in-vivo assays using a DNA
      affinity pre-incubation specificity test of recognition and chromatin
      immunoprecipitation showed that SATB2 specifically binds to histone deacetylase 1
      and metastasis-associated protein 2, members of the nucleosome-remodeling and
      histone deacetylase complex. Double immunohistochemistry showed that, in the
      developing rat neocortex, SATB2 is coexpressed with both proteins. Using a cell
      culture model, we showed that trichostatin A treatment, which blocks the
      activities of histone deacetylases, reverses the AT-rich dsDNA-dependent
      repressor effect of SATB2. These findings suggested that the molecular regulatory
      function of SATB2 involves modification of the chromatin structure. Semi
      quantitative chromatin immunoprecipitation analysis of cortices from SATB2 mutant
      and wild-type animals indicated that, in the knock-out brains, SATB2 is replaced
      in the chromatin-remodeling complex by AU-rich element RNA binding protein 1,
      another AT-rich DNA binding protein also expressed in differentiating cortical
      neurons. These results suggested that an altered chromatin structure, due to the
      presence of different AT-rich DNA binding proteins in the chromatin-remodeling
      complex, may contribute to the developmental abnormalities observed in the SATB2
      mutant animals. These findings also raised the interesting possibility that
      SATB2, along with other AT-rich DNA binding proteins, is involved in mediating
      epigenetic influences during cortical development.

PMID- 18333963
TI  - Sensitization of meningeal nociceptors: inhibition by naproxen.
AB  - Migraine attacks associated with throbbing (manifestation of peripheral
      sensitization) and cutaneous allodynia (manifestation of central sensitization)
      are readily terminated by intravenous administration of a non-selective
      cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central
      trigeminovascular neurons was also terminated in vivo by non-selective COX
      inhibition has led us to propose that COX inhibitors may act centrally in the
      dorsal horn. In the present study, we examined whether COX inhibition can also
      suppress peripheral sensitization in meningeal nociceptors. Using single-unit
      recording in the trigeminal ganglion in vivo, we found that intravenous infusion
      of naproxen, a non-selective COX inhibitor, reversed measures of sensitization
      induced in meningeal nociceptors by prior exposure of the dura to inflammatory
      soup (IS): ongoing activity of Adelta- and C-units and their response magnitude
      to mechanical stimulation of the dura, which were enhanced after IS, returned to
      baseline after naproxen infusion. Topical application of naproxen or the
      selective COX-2 inhibitor N-[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide
      (NS-398) onto the dural receptive field of Adelta- and C-unit nociceptors also
      reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura.
      The findings suggest that local COX activity in the dura could mediate the
      peripheral sensitization that underlies migraine headache.

PMID- 18333964
TI  - Ro5-4864 promotes neonatal motor neuron survival and nerve regeneration in adult
      rats.
AB  - The translocator protein (18 kDa; TSPO), formerly known as the peripheral
      benzodiazepine receptor, is an outer mitochondrial membrane protein that
      associates with the mitochondrial permeability transition pore to regulate both
      steroidogenesis and apoptosis. TSPO expression is induced in adult dorsal root
      ganglion (DRG) sensory neurons after peripheral nerve injury and a TSPO receptor
      ligand, Ro5-4864, enhances DRG neurite growth in vitro and axonal regeneration in
      vivo. We have now found that TSPO is induced in neonatal motor neurons after
      peripheral nerve injury and have evaluated its involvement in neonatal and adult
      sensory and motor neuron survival, and in adult motor neuron regeneration. The
      TSPO ligand Ro5-4864 rescued cultured neonatal DRG neurons from nerve growth
      factor withdrawal-induced apoptosis and protected neonatal spinal cord motor
      neurons from death due to sciatic nerve axotomy. However, Ro5-4864 had only a
      small neuroprotective effect on adult facial motor neurons after axotomy, did not
      delay onset or prolong survival in SOD1 mutant mice, and failed to protect adult
      DRG neurons from sciatic nerve injury-induced death. In contrast, Ro5-4864
      substantially enhanced adult facial motor neuron nerve regeneration and
      restoration of function after facial nerve axotomy. These data indicate a
      selective sensitivity of neonatal sensory and motor neurons to survival in
      response to Ro5-4864, which highlights that survival in injured immature neurons
      cannot necessarily predict success in adults. Furthermore, although Ro5-4864 is
      only a very weak promoter of survival in adult neurons, it significantly enhances
      regeneration and functional recovery in adults.

PMID- 18333966
TI  - Neuronal field potential in acute hippocampus slice recorded with transistor and
      micropipette electrode.
AB  - Arrays of planar electrodes are often applied to record spatial patterns of
      neuronal field potentials in acute brain slices. The approach is hampered by
      layers of inactive tissue caused by the cutting process and also by a film of
      bath electrolyte that may exist between the slice and the substrate. To address
      this issue, we used a micropipette electrode to measure the vertical profile of
      evoked field potentials across acute slices from mouse hippocampus. In this way,
      we found that the signal due to an excitatory postsynaptic potential (EPSP) at
      the bottom of the slice was about 40% of the maximum at its centre. The vertical
      profile was matched by a volume-conductor model with proper boundary conditions.
      Simultaneously, voltage transients caused by EPSPs were measured with a field
      effect transistor in the substrate. The transistor signals were in agreement with
      the evoked field potentials at the bottom of the slice. The study demonstrates:
      (i) that the loss of signal amplitude from the centre of a slice to the bottom is
      modest, despite an inactive tissue layer; and (ii) that in principle, planar
      sensors are able to record the field potential at the bottom of a slice. The
      results raise questions about the small voltages that are often observed with
      planar metal electrodes and about the reconstruction of the neuronal activity
      from field potentials at the bottom of acute slices using current-source density
      analysis.

PMID- 18333965
TI  - Increased striatal dopamine release and hyperdopaminergic-like behaviour in mice
      lacking both alpha-synuclein and gamma-synuclein.
AB  - Alpha-synuclein is intimately involved in the pathogenesis of Parkinson's
      disease, and has been implicated in the regulation of synthesis, release and
      reuptake of dopamine (DA). However, mice lacking members of the synuclein family
      have been reported to display no overt behavioural phenotype. This may be a
      result of compensatory upregulation of other synucleins during development. Here
      we report on behaviour and DA synapse function of alpha-synuclein null, gamma
      synuclein null, and alpha-gamma-synuclein double-null knockout mice. Double-null
      mice were hyperactive in a novel environment and alternated at a lower rate in a
      T-maze spontaneous alternation task, a phenotype reminiscent of mice expressing
      reduced levels of the DA transporter. To investigate a possible hyperdopaminergic
      phenotype in alpha-gamma-synuclein double-null mice, we used fast-scan cyclic
      voltammetry at carbon-fibre microelectrodes to assess DA release and reuptake in
      striatal slices from wild-type, alpha-null, gamma-null and double-null mice in
      real time. Double-null mice were found to have a twofold increase in the
      extracellular concentration of DA detected after discrete electrical stimuli in
      the striatum. By measuring the rate of reuptake of DA and tissue DA content in
      these animals, we showed that the observed increase in size of striatal DA
      transients was not attributable to a decrease in reuptake of DA via the DA
      transporter, and can not be attributed to an increase in tissue DA levels in the
      striatum. Rather, we propose that loss of both alpha- and gamma-synuclein causes
      an increase in release probability from dopaminergic synapses.

PMID- 18333967
TI  - Acetylcholine-induced seizure-like activity and modified cholinergic gene
      expression in chronically epileptic rats.
AB  - The entorhinal cortex (EC) plays an important role in temporal lobe epilepsy.
      Under normal conditions, the enriched cholinergic innervation of the EC modulates
      local synchronized oscillatory activity; however, its role in epilepsy is
      unknown. Enhanced neuronal activation has been shown to induce transcriptional
      changes of key cholinergic genes and thus alter cholinergic responses. To examine
      cholinergic modulations in epileptic tissue we studied molecular and
      electrophysiological cholinergic responses in the EC of chronically epileptic
      rats following exposure to pilocarpine or kainic acid. We confirmed that while
      the total activity of the acetylcholine (ACh)-hydrolysing enzyme,
      acetylcholinesterase (AChE) was not altered, epileptic rats showed alternative
      splicing of AChE pre-mRNA transcripts, accompanied by a shift from membrane-bound
      AChE tetramers to soluble monomers. This was associated with increased
      sensitivity to ACh application: thus, in control rats, ACh (10-100 microm)
      induced slow (< 1Hz), periodic events confined to the EC; however, in epileptic
      rats, ACh evoked seconds-long seizure-like events with initial appearance in the
      EC, and frequent propagation to neighbouring cortical regions. ACh-induced
      seizure-like events could be completely blocked by the non-specific muscarinic
      antagonist, atropine, and were partially blocked by the muscarinic-1 receptor
      antagonist, pirenzepine; but were not affected by the non-specific nicotinic
      antagonist, mecamylamine. Epileptic rats presented reduced transcript levels of
      muscarinic receptors with no evidence of mRNA editing or altered mRNA levels for
      nicotinic ACh receptors. Our findings suggest that altered cholinergic modulation
      may initiate seizure events in the epileptic temporal cortex.

PMID- 18333968
TI  - Psychophysiological responses to drug-associated stimuli in chronic heavy
      cannabis use.
AB  - Due to learning processes originally neutral stimuli become drug-associated and
      can activate an implicit drug memory, which leads to a conditioned arousing 'drug
      seeking' state. This condition is accompanied by specific psychophysiological
      responses. The goal of the present study was the analysis of changes in cortical
      and peripheral reactivity to cannabis as well as alcohol-associated pictures
      compared with emotionally significant drug-unrelated and neutral pictures in long
      term heavy cannabis users. Participants were 15 chronic heavy cannabis users and
      15 healthy controls. Verbal reports as well as event-related potentials of the
      electroencephalogram and skin conductance responses were assessed in a cue
      reactivity paradigm to determine the psychophysiological effects caused by drug
      related visual stimulus material. The evaluation of self-reported craving and
      emotional processing showed that cannabis stimuli were perceived as more arousing
      and pleasant and elicited significantly more cannabis craving in cannabis users
      than in healthy controls. Cannabis users also demonstrated higher cannabis
      stimulus-induced arousal, as indicated by significantly increased skin
      conductance and a larger late positivity of the visual event-related brain
      potential. These findings support the assumption that drug-associated stimuli
      acquire increased incentive salience in addiction history and induce conditioned
      physiological patterns, which lead to craving and potentially to drug intake. The
      potency of visual drug-associated cues to capture attention and to activate drug
      specific memory traces and accompanying physiological symptoms embedded in a
      cycle of abstinence and relapse--even in a 'so-called' soft drug--was assessed
      for the first time.

PMID- 18333969
TI  - Neuronal correlates of perceptual stability during eye movements.
AB  - We are usually unaware of retinal image motion resulting from our own movement.
      For instance, during slow-tracking 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 example of perceptual invariance is achieved by
      subtracting an internal reference signal, reflecting the eye movement, from the
      retinal motion signal. If the two cancel each other, visual objects, which do not
      move, will also be perceived as non-moving. If, however, the reference signal is
      too small or too large, a false eye movement-induced motion of the external
      world, the Filehne illusion, will be perceived. We have exploited our ability to
      manipulate the size of the reference signal in an attempt to identify neurons in
      the visual cortex of monkeys, influenced by the percept of self-induced visual
      motion or the reference signal rather than the retinal motion signal. We report
      here that such 'percept-related' neurons can already be found in the primary
      visual cortex area, although few in numbers. They become more frequent in areas
      middle temporal and medial superior temporal in the superior temporal sulcus, and
      comprise almost 50% of all neurons in area visual posterior sylvian (VPS) in the
      posterior part of the lateral sulcus. In summary, our findings suggest that our
      ability to perceive a visual world, which is stable despite self-motion, is based
      on a neuronal network, which culminates in the VPS located in the lateral sulcus
      below the classical dorsal stream of visual processing.

PMID- 18333970
TI  - Contextual integration the unusual way: a magnetoencephalographic study of
      responses to semantic violation in individuals with autism spectrum disorders.
AB  - Autism is a neurodevelopmental disorder associated with deficits in language and
      social communication. Behavioural studies indicate abnormal semantic organization
      in individuals with autism, but little is known about the neural mechanism
      underlying the processing of language in context. Magnetoencephalography was used
      to record neural responses in 11 able adults with autism spectrum disorders
      reading meaningful sentences and sentences ending with a semantically incongruous
      word (e.g. 'He sent a photo to the trumpet'). Spatially extended evoked signals
      at 400 ms (N4) and 750 ms (LPC), as well as synchronized gamma-oscillations,
      provided clear evidence for specific neuronal processes sensitive to sentence
      context that differed in individuals with autism compared with typically
      developing individuals (11 healthy volunteers). Amongst other differences, N4
      responses following incongruous words were weaker over left temporal cortices,
      whereas LPC responses to incongruous words and long-latency gamma-oscillations
      following congruous words were stronger over central and prefrontal regions in
      individuals with autism compared with the control group. Also, incongruous words
      elicited long-lasting gamma-oscillations above 40 Hz in the clinical group, but
      not in typically developing subjects. These findings may indicate unusual
      strategies for resolving semantic ambiguity in autism. Moreover, the observed
      gamma-band responses provide evidence for sustained cortical synchronization
      across segregated areas in individuals with autism, contrary to claims that a
      general deficit in either temporal binding or long-range connectivity may explain
      autism.

PMID- 18333971
TI  - Young children's spontaneous use of geometry in maps.
AB  - Two experiments tested whether 4-year-old children extract and use geometric
      information in simple maps without task instruction or feedback. Children saw
      maps depicting an arrangement of three containers and were asked to place an
      object into a container designated on the map. In Experiment 1, one of the three
      locations on the map and the array was distinct and therefore served as a
      landmark; in Experiment 2, only angle, distance and sense information specified
      the target container. Children in both experiments used information for distance
      and angle, but not sense, showing signature error patterns found in adults.
      Children thus show early, spontaneously developing abilities to detect geometric
      correspondences between three-dimensional layouts and two-dimensional maps, and
      they use these correspondences to guide navigation. These findings begin to chart
      the nature and limits of the use of core geometry in a uniquely human, symbolic
      task.

PMID- 18333972
TI  - The shape of controversy: what counts as an explanation of development?
      Introduction to the special section.

PMID- 18333973
TI  - Taking stock as theories of word learning take shape.
AB  - In this paper we consider the perceptual and conceptual contributions that shape
      early word learning, using research on the shape bias as a case in point. In our
      view, conceptual, linguistic, social-pragmatic, and perceptual sources of
      information influence one another powerfully and continuously in the service of
      word learning throughout infancy and early childhood. We articulate several key
      points of convergence and divergence between our theoretical perspective and that
      of the attentional learning account. Finally, we consider the broader
      implications of this debate for clarifying the forces that constrain development.

PMID- 18333974
TI  - Knowledge embedded in process: the self-organization of skilled noun learning.
AB  - Young children's skilled generalization of newly learned nouns to new instances
      has become the battleground for two very different approaches to cognition. This
      debate is a proxy for a larger dispute in cognitive science and cognitive
      development: cognition as rule-like amodal propositions, on the one hand, or as
      embodied, modal, and dynamic processes on the other. After a brief consideration
      of this theoretical backdrop, we turn to the specific task set before us: an
      overview of the Attentional Learning Account (ALA) of children's novel noun
      generalizations, the constrained set of experimental results to be explained, and
      our explanation of them. We conclude with a consideration of what all of this
      implies for a theory of cognitive development.

PMID- 18333975
TI  - The shape of thought.
AB  - When children learn the name of a novel object, they tend to extend that name to
      other objects similar in shape - a phenomenon referred to as the shape bias. Does
      the shape bias stem from learned associations between names and categories of
      objects, or does it derive from more general properties of children's
      understanding of language and the world? We argue here for the second
      alternative, presenting evidence that the shape bias emerges early in
      development, is not limited to names, and is intimately related to how children
      make sense of categories.

PMID- 18333976
TI  - Confronting complexity: insights from the details of behavior over multiple
      timescales.
AB  - Young children tend to generalize novel names for novel solid objects by
      similarity in shape, a phenomenon dubbed 'the shape bias'. We believe that the
      critical insights needed to explain the shape bias in particular, and cognitive
      development more generally, come from Dynamic Systems Theory. We present two
      examples of recent work focusing on the real-time decision processes that
      underlie performance in the tasks used to measure the shape bias. We show how
      this work, and the dynamic systems perspective, sheds light on the controversy
      over the origins and development of the shape bias. In addition, we suggest that
      this dynamic systems perspective provides the right level for explanations of
      development because it requires a focus on the details of behavior over multiple
      timescales.

PMID- 18333977
TI  - The shape of things to come: the future of the shape bias controversy.

PMID- 18333978
TI  - The shape bias: an important piece in a bigger puzzle.

PMID- 18333979
TI  - Verbal self-instructions in task switching: a compensatory tool for action
      control deficits in childhood and old age?
AB  - This study examined the influence of verbal self-instructions on age differences
      in task switching. Task-switching ability, measured as the difference between
      performance in single-task blocks and in mixed-task blocks in which participants
      switch between two tasks (mixing costs), increases during childhood and decreases
      in old age. To measure the influence of language on task switching, we compared
      conditions in which participants either (a) named the next task to be performed
      (i.e. task-relevant verbalization), (b) verbalized words not related to the task
      at hand (i.e. task-irrelevant verbalization), or (c) did not verbalize (control
      condition). Results indicated that mixing costs were substantially reduced under
      task-relevant verbalization and increased under task-irrelevant verbalization.
      Moreover, age-related differences in mixing costs were increased when the use of
      inner speech was disrupted and were reduced when participants performed task
      relevant verbalization. These findings suggest that verbal self-instructions are
      a useful tool for retrieving the next task goal and for reducing action-control
      deficits in younger children and older adults.

PMID- 18333980
TI  - Functional neuroimaging of speech perception during a pivotal period in language
      acquisition.
AB  - A pivotal period in the development of language occurs in the second year of
      life, when language comprehension undergoes rapid acceleration. However, the
      brain bases of these advances remain speculative as there is currently no
      functional magnetic resonance imaging (fMRI) data from healthy, typically
      developing toddlers at this age. We investigated the neural basis of speech
      comprehension in this critical age period by measuring fMRI activity during
      passive speech comprehension in 10 toddlers (mean +/- SD; 21 +/- 4 mo) and 10 3
      year-old children (39 +/- 3 mo) during natural sleep. During sleep, the children
      were presented passages of forward and backward speech in 20-second blocks
      separated by 20-second periods of no sound presentation. Toddlers produced
      significantly greater activation in frontal, occipital, and cerebellar regions
      than 3-year-old children in response to forward speech. Our results suggest that
      rapid language acquisition during the second year of life may require the
      utilization of frontal, cerebellar, and occipital regions in addition to
      classical superior temporal language areas. These findings are consistent with
      the interactive specialization hypothesis, which proposes that cognitive
      abilities develop from the interaction of brain regions that include and extend
      beyond those used in the adult brain.

PMID- 18333981
TI  - An empirical validation of a dynamic systems model of interaction: do children of
      different sociometric statuses differ in their dyadic play?
AB  - Studying short-term dynamic processes and change mechanisms in interaction yields
      important knowledge that contributes to understanding long-term social
      development of children. In order to get a grip on this short-term dynamics of
      interaction processes, the authors made a dynamic systems model of dyadic
      interaction of children during one play session. The control parameters of the
      model relate to children's goal-directedness, concerns, emotional appraisals,
      social power, and social competence. Three groups of dyads of different
      sociometric statuses are represented by specific control parameter values. The
      model's order parameters consist of children's emotional expressions and other-
      versus self-directed actions. This article describes the empirical validation of
      the model and the methods needed for such validation. It focuses on the model's
      predictions of averages and distributions of the major variables, of the
      occurrence of attractors and power law distributions, and on the model's
      sensitivity. Overall, the model fits the empirical data well. In the discussion,
      we reflect on the developmental and methodological implications for explaining
      social interaction on the short-term as well as on the long-term time scale. In
      addition, implications for intervention and assessment are presented, in
      particular relating to the problem of rejection.

PMID- 18333982
TI  - Bilingual experience and executive functioning in young children.
AB  - Advanced inhibitory control skills have been found in bilingual speakers as
      compared to monolingual controls (Bialystok, 1999). We examined whether this
      effect is generalized to an unstudied language group (Spanish-English bilingual)
      and multiple measures of executive function by administering a battery of tasks
      to 50 kindergarten children drawn from three language groups: native bilinguals,
      monolinguals (English), and English speakers enrolled in second-language
      immersion kindergarten. Despite having significantly lower verbal scores and
      parent education/income level, Spanish-English bilingual children's raw scores
      did not differ from their peers. After statistically controlling for these
      factors and age, native bilingual children performed significantly better on the
      executive function battery than both other groups. Importantly, the relative
      advantage was significant for tasks that appear to call for managing conflicting
      attentional demands (Conflict tasks); there was no advantage on impulse-control
      (Delay tasks). These results advance our understanding of both the
      generalizability and specificity of the compensatory effects of bilingual
      experience for children's cognitive development.

PMID- 18333983
TI  - Children's working understanding of the knowledge gained from seeing and feeling.
AB  - In three experiments (N = 48 3- to 4-year olds; 100 3- to 5-year olds; 54 4-year
      olds), children who could see or feel a target toy, recognized when they had
      sufficient information to answer 'Which one is it?' and when they needed
      additional access. They were weaker at taking the informative modality of access
      when the choice was between seeing more of a partially visible toy and feeling
      it; at doing so when the target was completely hidden; and at reporting seeing or
      feeling as their source of knowledge of the target's identity having experienced
      both. Working understanding of the knowledge gained from seeing and feeling
      (identifying the target efficiently) was not necessarily in advance of explicit
      understanding (reporting the informative source).

PMID- 18333984
TI  - Impact of language on development of auditory-visual speech perception.
AB  - The McGurk effect paradigm was used to examine the developmental onset of inter
      language differences between Japanese and English in auditory-visual speech
      perception. Participants were asked to identify syllables in audiovisual (with
      congruent or discrepant auditory and visual components), audio-only, and video
      only presentations at various signal-to-noise levels. In Experiment 1 with two
      groups of adults, native speakers of Japanese and native speakers of English, the
      results on both percent visually influenced responses and reaction time supported
      previous reports of a weaker visual influence for Japanese participants. In
      Experiment 2, an additional three age groups (6, 8, and 11 years) in each
      language group were tested. The results showed that the degree of visual
      influence was low and equivalent for Japanese and English language 6-year-olds,
      and increased over age for English language participants, especially between 6
      and 8 years, but remained the same for Japanese participants. This may be related
      to the fact that English language adults and older children processed visual
      speech information relatively faster than auditory information whereas no such
      inter-modal differences were found in the Japanese participants' reaction times.

PMID- 18333985
TI  - Atypical neural functions underlying phonological processing and silent rehearsal
      in children who stutter.
AB  - Phonological processing was examined in school-age children who stutter (CWS) by
      assessing their performance and recording event-related brain potentials (ERPs)
      in a visual rhyming task. CWS had lower accuracy on rhyming judgments, but the
      cognitive processes that mediate the comparisons of the phonological
      representations of words, as indexed by the rhyming effect (RE) ERP, were similar
      for the stuttering and normally fluent groups. Thus the lower behavioral accuracy
      of rhyming judgments by the CWS could not be attributed to that particular stage
      of processing. Instead, the neural functions for processes preceding the RE,
      indexed by the N400 and CNV elicited by the primes and the N400 elicited by the
      targets, suggest atypical processing that may have resulted in less efficient,
      less accurate rhyming judgment for the CWS. Based on the present results, it
      seems likely that the neural processes related to phonological rehearsal and
      target word anticipation, as indexed by the CNV, are distinctive for CWS at this
      age. Further, it is likely that the relative contributions of the left and right
      hemispheres differ in CWS in the stage of processing when linguistic integration
      occurs, as indexed by the N400. Taken together, these results suggest that CWS
      may be less able to form and retain a stable neural representation of the prime
      onset and rime as they anticipate the target presentation, which may lead to
      lower rhyming judgment accuracy.

PMID- 18333986
TI  - Declaration of the High Tatras.

PMID- 18333987
TI  - Effect of inhaled formaldehyde on learning and memory of mice.
AB  - In this study, we investigated the effect of inhaled formaldehyde on learning and
      memory capacity. After exposure to 0 (control), 1 and 3 mg/m(3) of gaseous
      formaldehyde respectively, the behavior of mice in a Morris water maze, the
      expression of NR1, NR2B mRNA and oxidative damage levels in mice brain were
      analyzed. The water maze performance, the activities of dismutase superoxide
      (SOD) and levels of glutathione (GSH) decreased significantly in 3 mg/m(3) group
      (P < 0.01, compared with control group); while malondialdehyde (MDA) contents and
      expression of NR1 and NR2B genes increased significantly after exposure to 3
      mg/m(3) of gaseous formaldehyde (P < 0.05, <0.01, <0.01, compared with control
      group). These findings indicate that inhaled formaldehyde negatively affects
      learning and memory at 3 mg/m(3) of gaseous formaldehyde but not at lower levels.
      Oxidative stress-induced neuron damages in the brain may be the possible
      mechanism for these effects. PRACTICAL IMPLICATIONS: This study indicates that
      inhaled formaldehyde starts to negatively affect learning and memory at a middle
      concentration of formaldehyde without interference of other indoor air
      pollutants. Oxidative damage, and the alteration of NMDA receptor expression,
      which were induced by formaldehyde inhalation, may be the possible mechanism for
      gaseous formaldehyde-induced neurotoxicity.

PMID- 18333988
TI  - Long-term reliability in reporting of childhood pets by adults interviewed twice,
      9 years apart. Results from the European Community Respiratory Health Survey I
      and II.
AB  - Investigation of long-term effects of childhood pet exposure is usually based on
      retrospective information provided by adults, while there is little knowledge
      about the reliability in adult reporting of childhood events. We analyzed 8287
      adults interviewed about childhood pets twice, on average nine years apart, in
      the European Community Respiratory Health Survey. Agreement between the surveys
      in reporting of childhood cats, dogs and birds were investigated with kappa
      statistics, and potential effects of disease status on agreement were analyzed
      with kappa statistics and multiple logistic regressions. Cats, dogs and birds in
      childhood were reported by 44, 41 and 38%, respectively. Cohen's kappa for
      agreement in adult reporting of childhood pets was 0.714 (95% CI=0.698-0.729) for
      cat, 0.709 (0.691-0.722) for dog, and 0.606 (0.591-0.626) for bird. Thus,
      agreement was significantly higher for reporting of cat and dog than for bird.
      Adult wheeze, asthma or atopy did not influence agreement. Neither did adult cat
      sensitization influence agreement in adult reporting of childhood cat. Childhood
      factors such as moving house <5 years, or growing up as a single child, in a
      large family or in a rural area, were associated with poorer agreement, while
      adult factors were unrelated to agreement. PRACTICAL IMPLICATIONS: Long-term
      reliability in adult reporting of childhood pets was substantial, and not
      influenced by disease status. Thus, collection of information about childhood
      pets from adults appears to be reliable for the purpose of studying adult
      allergic disease. Future studies should consider that the reliability was higher
      for a more important childhood event and influenced by childhood rather than
      adult characteristics. Imperfect reliability contributed to underestimation of
      the effects of pets on adult allergy; i.e. with a kappa of 0.71, a true odds
      ratio (OR) of 0.80 would be attenuated to 0.86. Future studies should account for
      non-differential misclassification error.

PMID- 18333989
TI  - Reduction in personal exposures to particulate matter and carbon monoxide as a
      result of the installation of a Patsari improved cook stove in Michoacan Mexico.
AB  - The impact of an improved wood burning stove (Patsari) in reducing personal
      exposures and indoor concentrations of particulate matter (PM(2.5)) and carbon
      monoxide (CO) was evaluated in 60 homes in a rural community of Michoacan,
      Mexico. Average PM(2.5) 24-h personal exposure was 0.29 mg/m(3) and mean 48-h
      kitchen concentration was 1.269 mg/m(3) for participating women using the
      traditional open fire (fogon). If these concentrations are typical of rural
      conditions in Mexico, a large fraction of the population is chronically exposed
      to levels of pollution far higher than ambient concentrations found by the
      Mexican government to be harmful to human health. Installation of an improved
      Patsari stove in these homes resulted in 74% reduction in median 48-h PM(2.5)
      concentrations in kitchens and 35% reduction in median 24-h PM(2.5) personal
      exposures. Corresponding reductions in CO were 77% and 78% for median 48-h
      kitchen concentrations and median 24-h personal exposures, respectively. The
      relationship between reductions in median kitchen concentrations and reductions
      in median personal exposures not only changed for different pollutants, but also
      differed between traditional and improved stove type, and by stove adoption
      category. If these reductions are typical, significant bias in the relationship
      between reductions in particle concentrations and reductions in health impacts
      may result, if reductions in kitchen concentrations are used as a proxy for
      personal exposure reductions when evaluating stove interventions. In addition,
      personal exposure reductions for CO may not reflect similar reductions for
      PM(2.5). This implies that PM(2.5) personal exposure measurements should be
      collected or indoor measurements should be combined with better time-activity
      estimates, which would more accurately reflect the contributions of indoor
      concentrations to personal exposures. PRACTICAL IMPLICATIONS: Installation of
      improved cookstoves may result in significant reductions in indoor concentrations
      of carbon monoxide and fine particulate matter (PM(2.5)), with concurrent but
      lower reductions in personal exposures. Significant errors may result if
      reductions in kitchen concentrations are used as a proxy for personal exposure
      reductions when evaluating stove interventions in epidemiological investigations.
      Similarly, time microenvironment activity models in these rural homes do not
      provide robust estimates of individual exposures due to the large spatial
      heterogeneity in pollutant concentrations and the lack of resolution of time
      activity diaries to capture movement through these microenvironments.

PMID- 18333990
TI  - Removal of viable bioaerosol particles with a low-efficiency HVAC filter enhanced
      by continuous emission of unipolar air ions.
AB  - Continuous emission of unipolar ions has been shown to improve the performance of
      respirators and stationary filters challenged with non-biological particles. In
      this study, we investigated the ion-induced enhancement effect while challenging
      a low-efficiency heating, ventilation and air-conditioning (HVAC) filter with
      viable bacterial cells, bacterial and fungal spores, and viruses. The aerosol
      concentration was measured in real time. Samples were also collected with a
      bioaerosol sampler for viable microbial analysis. The removal efficiency of the
      filter was determined, respectively, with and without an ion emitter. The
      ionization was found to significantly enhance the filter efficiency in removing
      viable biological particles from the airflow. For example, when challenged with
      viable bacteria, the filter efficiency increased as much as four- to fivefold.
      For viable fungal spores, the ion-induced enhancement improved the efficiency by
      a factor of approximately 2. When testing with virus-carrying liquid droplets,
      the original removal efficiency provided by the filter was rather low: 9.09 +/-
      4.84%. While the ion emission increased collection about fourfold, the efficiency
      did not reach 75-100% observed with bacteria and fungi. These findings, together
      with our previously published results for non-biological particles, demonstrate
      the feasibility of a new approach for reducing aerosol particles in HVAC systems
      used for indoor air quality control. PRACTICAL IMPLICATIONS: Recirculated air in
      HVAC systems used for indoor air quality control in buildings often contains
      considerable number of viable bioaerosol particles because of limited efficiency
      of the filters installed in these systems. In the present study, we investigated 
      using aerosolized bacterial cells, bacterial and fungal spores, and virus
      carrying particles - a novel idea of enhancing the performance of a low
      efficiency HVAC filter utilizing continuous emission of unipolar ions in the
      filter vicinity. The findings described in this paper, together with our
      previously published results for non-biological particles, demonstrate the
      feasibility of the newly developed approach.

PMID- 18333991
TI  - Microbial volatile organic compounds in the air of moldy and mold-free indoor
      environments.
AB  - A single-blinded study was performed to analyze whether indoor environments with
      and without mold infestation differ significantly in microbial volatile organic
      compounds (MVOC) concentrations. Air sampling for MVOC was performed in 40
      dwellings with evident mold damage and in 44 dwellings, where mold damage was
      excluded after a thorough investigation. The characteristics of the dwellings,
      climatic parameters, airborne particles and air exchange rates (AER) were
      recorded. The parameters mold status, characteristics of the interiors and
      measured climatic parameters were included in the multiple regression model. The
      results show no significant association between most of the analyzed MVOC and the
      mold status. Only the compounds 2-methyl-1-butanol and 1-octen-3-ol indicated a
      statistically significant, but weak association with the mold status. However,
      the concentrations of the so-called MVOC were mainly influenced by other indoor
      factors. 2-Methylfuran and 3-methylfuran, often used as main indicators for mold
      damage, had a highly significant correlation with the smoking status. These
      compounds were also significantly correlated with the humidity and the AER. The
      compounds 3-methyl-1-butanol, 2-hexanone, 3-heptanone and dimethyl disulfide were
      weakly correlated with the recorded parameters, the humidity being the strongest
      influencing factor. Only 2-methyl-1-butanol and 1-octen-3-ol showed a
      statistically significant association with the mold status; however, only a small
      portion (10% in this case) of the total variability could be explained by the
      predictor mold status; they do not qualify as indicator compounds, because such
      minor correlations lead to a too excessive part of incorrect classifications,
      meaning that the diagnostic sensitivity and specificity of these compounds are
      too low. PRACTICAL IMPLICATIONS: The assumption that mold infestations might be
      detected by microbial VOC emissions must be considered with great reservation.
      The major part of the total variability of the measured MVOC concentrations
      originates from not known influencing factors and/or from factors not directly
      associated with the mold status of the dwellings (confounders). More specific and
      sensitive markers for the assessment of the mold status should be found, if the
      screening for mold infestations should be performed by volatile organic
      compounds.

PMID- 18333992
TI  - Respiratory inflammatory responses among occupants of a water-damaged office
      building.
AB  - The National Institute for Occupational Safety and Health (NIOSH) received a
      request for evaluation of a water-damaged office building which housed
      approximately 1300 employees. Workers reported respiratory conditions that they
      perceived to be building related. We hypothesized that these symptoms were
      associated with airways inflammation. To test this hypothesis, we assessed
      airways inflammation in employees using exhaled breath condensate (EBC) and the
      fraction of exhaled nitric oxide (FENO). In September 2001, a health
      questionnaire was offered to all employees. Based on this questionnaire, NIOSH
      invited 356 symptomatic and asymptomatic employees to participate in a medical
      survey. In June 2002, these employees were offered questionnaire, spirometry,
      methacholine challenge test, allergen skin prick testing, EBC and FENO. FENO or
      EBC were completed by 239 participants. As smoking is highly related to the
      measurements that we used in this study, we included only the 207 current non
      smokers in the analyses. EBC interleukin-8 (IL-8) levels, but not nitrite, were
      significantly higher among workers with respiratory symptoms and in the physician
      diagnosed asthmatic group. Of the analyses assessed, EBC IL-8 showed the most
      significant relationship with a number of symptoms and physician-diagnosed
      asthma. PRACTICAL IMPLICATIONS: Implementation of exhaled breath condensate and
      exhaled nitric oxide in indoor air quality problems.

PMID- 18333993
TI  - Air filter materials, outdoor ozone and building-related symptoms in the BASE
      study.
AB  - Used ventilation air filters have been shown to reduce indoor environmental
      quality and worker performance and increase symptoms, with effects stronger after
      reaction of filters with ozone. We analyzed data from the US EPA Building
      Assessment Survey and Evaluation (BASE) study to determine if ozone and specific
      filter media have interactive effects on building-related symptoms (BRS). We
      analyzed a subset of 34 buildings from the BASE study of 100 US office buildings
      to determine the separate and joint associations of filter medium
      [polyester/synthetic (PS) or fiberglass (FG)] and outdoor ozone concentration
      (above/below the median, 67.6 microg/m(3)) with BRS. Using logistic regression
      models and general estimating equations, we estimated odds ratios (ORs) and 95%
      confidence intervals for the association of filter medium, ozone, and filter
      medium x ozone with BRS. Relative to FG + low ozone, PS alone or high ozone
      alone, were each significantly (P < 0.05) associated only with fatigue/difficulty
      concentrating (ORs = 1.93 and 1.54, respectively). However, joint exposure to
      both PS + high ozone, relative to FG + low ozone, had significant associations
      with lower and upper respiratory, cough, eye, fatigue, and headache BRS (ORs
      ranged from 2.26 to 5.90). Joint ORs for PS + high ozone for lower and upper
      respiratory and headache BRS were much greater than multiplicative, with
      interaction P-values <0.10. Attributable risk proportion (ARP) estimates indicate
      that removing both risk factors might, given certain assumptions, reduce BRS by
      26-62%. These findings suggest possible adverse health consequences from chemical
      interactions between outdoor ozone and PS filters in buildings. Results need
      confirmation before recommending changes in building operation. However, if
      additional research confirms causal relationships, ARP estimates indicate that
      appropriate filter selection may substantially reduce BRS in buildings,
      especially in high-ozone areas. PRACTICAL IMPLICATIONS: The results indicate that
      a better understanding of how filters interact with their environment is needed.
      While the mechanism is unknown and these findings need to be replicated, they
      indicate that the joint risk of BRS from polyester/synthetic filters and outdoor
      ozone above 67.6 microg/m(3) is much greater than the risk from each alone. These
      findings suggest potential reductions in BRS from appropriate selection of
      ventilation filter media or implementing strategies to reduce ozone entrained in
      building ventilation systems. If the relationships were found to be causal,
      filter replacement and ozone abatement should be undertaken.

PMID- 18333994
TI  - Outdoor ozone and building-related symptoms in the BASE study.
AB  - Reactions between ozone and indoor contaminants may influence human health and
      indoor air quality. The U.S. EPA Building Assessment Survey and Evaluation (BASE)
      study data were analyzed for associations between ambient ozone concentrations
      and building-related symptom (BRS) prevalence. Multiple logistic regression (MLR)
      models, adjusted for personal, workplace, and environmental variables, revealed
      positive relationships (P < 0.05) between ambient ozone concentrations and upper
      respiratory (UR), dry eyes, neurological and headache BRS (odds ratios ranged
      from 1.03 to 1.04 per 10 mug/m(3) increase in ambient ozone concentrations).
      Other BRS had marginally significant relationships with ambient ozone (P < 0.10).
      A linear dose-response in UR symptoms was observed with increasing ambient ozone
      (P = 0.03); most other symptoms showed similar but not statistically significant
      trends. Ambient ozone correlated with indoor concentrations of some aldehydes, a
      pattern suggesting the occurrence of indoor ozone chemistry. Coupled with the MLR
      ambient ozone-BRS analysis, this correlation is consistent with the hypothesis
      that ozone-initiated indoor reactions play an important role in indoor air
      quality and building occupant health. Replication with increased statistical
      power and with longitudinal data is needed. If the observed associations are
      confirmed as causal, ventilation system ozone removal technologies could reduce
      UR BRS prevalence when higher ambient ozone levels are present. PRACTICAL
      IMPLICATIONS: This paper provides strong statistical evidence that supports (but
      does not prove) the hypothesis that ozone entrained into buildings from the
      outdoor air is involved in increasing the frequency that occupants experience and
      a range of upper and lower respiratory, mucosal and neurological symptoms by as
      much as a factor of 2 when ambient ozone levels increase from those found in low
      ozone regions to those typical of high-ozone regions. Although replication is
      needed, the implication is that reducing the amount of ozone entrained into
      building ventilation systems, either by ambient pollution reduction or engineered
      gas-phase filtration, may substantially reduce the prevalence of these symptoms
      experienced by occupants.

PMID- 18333995
TI  - Patch clamp characterization of a non-selective cation channel of ER membranes
      purified from Beta vulgaris taproots.
AB  - The ER fraction from red beet taproot was purified on sucrose gradient and giant
      liposomes, suitable for patch clamping, were formed by dehydration-rehydration of
      the lipid film. Single-channel recordings on excised and attached patches
      revealed a large conductance (165 pS) cation (P(Cl-)/P(K+) < 0.03) channel with
      equal conductance and relative permeability for Na+ and K+. This non-selective
      cation channel was also highly permeable for Ca2+. We failed to detect any single
      channel currents activated by a direct application of d-myo-inositol 1,4,5
      trisphosphate, despite the fact that the ER membranes were native.

PMID- 18333996
TI  - A high-grain protein content locus on barley (Hordeum vulgare) chromosome 6 is
      associated with increased flag leaf proteolysis and nitrogen remobilization.
AB  - Leaf senescence and nitrogen remobilization from senescing tissues are two
      important factors determining grain protein content (GPC) in cereals. We compared
      near-isogenic barley (Hordeum vulgare L.) germplasm varying in the allelic state
      of a major GPC quantitative trait locus on chromosome 6, delineated by molecular
      markers HVM74 and ABG458 and explaining approximately 46% of the variability in
      this trait. High GPC was consistently associated with earlier whole-plant
      senescence. SDS-PAGE and immunoblot analysis of flag leaf proteins indicated
      earlier leaf protein [including ribulose-1,5-bisphosphate carboxylase/oxygenase
      (Rubisco)] degradation in high-GPC germplasm. This was accompanied by enhanced
      availability of ammonium and glutamine in developing kernels, suggesting
      increased phloem retranslocation of nitrogen. Based on previous microarray
      analysis, we performed a detailed expression study of six leaf genes, tentatively
      involved in plastidial proteolysis, vacuolar proteolysis, intermediary N
      metabolism and N transport. All of these were upregulated in high-GPC barley,
      mostly around 21 to 28 days past anthesis, prior to or around the time
      demonstrating maximal differences in leaf protein (including Rubisco) levels.
      Therefore, these genes represent potential targets to manipulate grain protein
      accumulation. It appears likely that their functional analysis will enhance our
      understanding of whole-plant N recycling. Additionally, earlier leaf
      (photosynthetic) protein degradation may lead to reduced N carbon assimilation in
      high-GPC germplasm, explaining past studies demonstrating a negative correlation
      between GPC and yield.

PMID- 18333997
TI  - Annual rainfall does not directly determine the carbon isotope ratio of leaves of
      Eucalyptus species.
AB  - Leaf carbon isotope discrimination (delta13C) was widely considered to directly
      reflect the rainfall environment in which the leaf developed, but recent
      observations have queried this. The relationship between delta13C and rainfall
      was explored in Eucalyptus species growing along a rainfall gradient in
      Australia. The leaves of 43 species of Eucalyptus and the closely related
      Corymbia species produced in 2003 were sampled in September 2004 at 50 sites and
      grouped into 15 locations along a rainfall gradient in southwest Western
      Australia. At 24 sites, the same species and same trees were sampled as in a
      study in September 2003 when leaves produced in 2002 were sampled. The rainfall
      in 2004 was on average 190 mm (range 135-270 mm) higher at all locations than in
      2003. In the leaves sampled in 2004, the mean carbon isotope discrimination
      (delta13C) across the 15 locations decreased 2.9 per thousand per 1000 mm of
      rainfall, the specific leaf area (SLA) increased by 2.9 m2 kg(-1) per 1000 mm of
      rainfall and the nitrogen (N) content decreased by 1.56 g m(-2) per 1000 mm of
      rainfall. In contrast, a comparison between the leaves produced in the drier 2002
      year compared with the wetter 2003 year showed that there was a strong
      correlation (r2= 0.85) between the SLA values between years and a trend for
      higher values with increasing SLA, but the values of delta(13)C were on average
      only 0.38 per thousand lower (more negative) at all locations in the wetter year,
      equivalent to a decrease of 2.0 per thousand per 1000 mm of rainfall. The results
      suggest that while there may be constitutive differences in leaf morphology, SLA
      and N content per unit area, increasing rainfall or cloudiness associated with
      higher rainfall increases SLA and decreases N content per unit area. We conclude
      that rainfall does not directly influence delta13C, but induces leaf
      morphological and physiological changes that affect the resultant delta13C.

PMID- 18333998
TI  - Low leaf hydraulic conductance associated with drought tolerance in soybean.
AB  - Lack of water is the most serious environmental constraint on agricultural
      production. More efficient use of water resources is a key solution for increased
      plant productivity in water-deficit environments. We examined the hydraulic
      characteristics of a 'slow wilting' phenotype in soybean (Glycine max Merr.), PI
      416937, which has been shown to have relatively constant transpiration rates
      above a threshold atmospheric vapor pressure deficit (VPD). The VPD response of
      PI 416937 was confirmed. Three experiments are reported to examine the hypothesis
      that the VPD response was a result of low hydraulic conductance in leaves as
      compared to two other soybean genotypes. Results are reported from experiments to
      measure transpiration response to VPD when xylem water potential was maintained
      at zero, leaf rehydration response and leaf carbon assimilation response to
      petiole cutting. Major interspecific differences in leaf hydraulic properties
      were observed. The observed low leaf hydraulic conductance in PI 416937 is
      consistent with an increased water use efficiency, and an increased water
      conservation by limiting transpiration rates under high evaporative conditions
      but allowing normal gas exchange rates under more moderate evaporative
      conditions.

PMID- 18333999
TI  - Antioxidant enzymatic activity is linked to waterlogging stress tolerance in
      citrus.
AB  - Soil flooding constitutes a seasonal factor that negatively affects plant
      performance and crop yields. In this work, the relationship between oxidative
      damage and flooding sensitivity was addressed in three citrus genotypes with
      different abilities to tolerate waterlogging. We examined leaf visible damage,
      oxidative damage in terms of malondialdehyde (MDA) concentration, leaf proline
      concentration, leaf and root ascorbate and glutathione contents and the
      antioxidant enzyme activities superoxide dismutase (EC 1.15.1.1), ascorbate
      peroxidase (EC 1.11.1.11), catalase (EC 1.11.1.6) and glutathione reductase (EC
      1.8.1.7). No differences in the extent of oxidative damage relative to controls
      were found among genotypes. However, a different ability to delay the apparition
      of oxidative damage was associated to a higher tolerance to waterlogging. This
      ability was linked to an enhanced activated oxygen species' scavenging capacity
      in terms of an increased antioxidant enzyme activity and higher content in polar
      antioxidant compounds. Therefore, the existence of a direct relationship between
      stress sensitivity and the early accumulation of MDA is proposed. In addition,
      data indicate that the protective role of proline has to be considered minimal as
      its accumulation was inversely correlated with tolerance to the stress. The
      positive antioxidant response in Carrizo citrange (Poncirus trifoliata L. Raf. x
      Citrus sinensis L. Osb.) and Citrumelo CPB 4475 (Poncirus trifoliata L. Raf. x
      Citrus paradisi L. Macf.) might be responsible for a higher tolerance to flooding
      stress, whereas in Cleopatra mandarin (Citrus reshni Hort. Ex Tan.), the early
      accumulation of MDA seems to be associated to an impaired ability for H2O2
      scavenging.

PMID- 18334000
TI  - Effects of long-term chilling on ultrastructure and antioxidant activity in
      leaves of two cucumber cultivars under low light.
AB  - Cucumber (Cucumis sativus L.) cv. Xintaimici (a chilling-resistant cultivar) and
      cv. Jinyan no. 4 (a chilling-sensitive cultivar) were subjected to two
      temperatures (15/15 and 25/18 degrees C) under low light (100 mumol m(-2) s(-1))
      to understand the relationship between ultrastructural changes and the
      antioxidant abilities caused by low temperature (15/15 degrees C). We also aimed
      to find indicators for chilling resistance that could be used on a routine basis
      in breeding programs of greenhouse crops. At the 15/15 degrees C treatment, the
      membranes of chloroplast, mitochondrion, ER and plasma were not significantly
      changed in Xintaimici, whereas they were seriously affected in Jinyan no. 4. This
      result was consistent with the changes of malonaldehyde in chilling-stressed
      cucumber leaves. The antioxidant activities were changed under low temperature
      according to cultivar-expected resistance, relating in part to the described
      ultrastructural changes. The activities of superoxide dismutase (EC 1.15.1.1) and
      guaiacol peroxidase (EC 1.11.1.7) increased in chilling-stressed leaves of both
      cultivars, but the two enzymes were not responsible for the difference between
      cucumber cultivars. At 15/15 degrees C, contents of GSH and activities of
      glutathione reductase (GR, EC 1.6.4.2) increased more in leaves of Xintaimici
      than in those of Jinyan no. 4, while catalase (CAT, EC 1.11.1.6) activities
      decreased less. GSH, GR and CAT were affected by low temperature and cultivars
      and correlated with the difference in ultrastructure between chilling-stressed
      cucumber cultivars. We propose that the three antioxidants might be therefore
      used as biochemical indicators to screen chilling-resistant cucumber cultivars.

PMID- 18334001
TI  - Boric acid and salinity effects on maize roots. Response of aquaporins ZmPIP1 and
      ZmPIP2, and plasma membrane H+-ATPase, in relation to water and nutrient uptake.
AB  - Under saline conditions, an optimal cell water balance, possibly mediated by
      aquaporins, is important to maintain the whole-plant water status. Furthermore,
      excessive accumulation of boric acid in the soil solution can be observed in
      saline soils. In this work, the interaction between salinity and excess boron
      with respect to the root hydraulic conductance (L(0)), abundance of aquaporins
      (ZmPIP1 and ZmPIP2), ATPase activity and root sap nutrient content, in the highly
      boron- and salt-tolerant Zea mays L. cv. amylacea, was evaluated. A
      downregulation of root ZmPIP1 and ZmPIP2 aquaporin contents were observed in NaCl
      treated plants in agreement with the L(0) measurements. However, in the H3BO3
      treated plants differences in the ZmPIP1 and ZmPIP2 abundance were observed. The
      ATPase activity was related directly to the amount of ATPase protein and Na+
      concentration in the roots, for which an increase in NaCl- and H3BO3+ NaCl
      treated plants was observed with respect to untreated and H3BO3-treated plants.
      Although nutrient imbalance may result from the effect of salinity or H3BO3
      alone, an ameliorative effect was observed when both treatments were applied
      together. In conclusion, our results suggest that under salt stress, the activity
      of specific membrane components can be influenced directly by boric acid,
      regulating the functions of certain aquaporin isoforms and ATPase as possible
      components of the salinity tolerance mechanism.

PMID- 18334002
TI  - Equivalent pore radii of hydrophilic foliar uptake routes in stomatous and
      astomatous leaf surfaces--further evidence for a stomatal pathway.
AB  - Foliar uptake pathways for hydrophilic solutes were studied by the analysis of co
      uptake of 15N-labelled urea, NH4+ or NO3- and 13C-labelled sucrose across leaf
      surfaces of various plant species. Uptake of N (y) and sucrose (x) were strongly
      correlated. Curvilinear regression revealed significantly positive intercepts
      with the y-axis indicating the involvement of a sucrose-excluding pathway
      consisting of small pores with radii <0.5 nm. Depending on plant species, N
      source, leaf side and aperture of stomata, these small pores accounted for 6-62%
      of total N uptake. Regression analysis revealed that in stomatous leaf surfaces
      of Vicia faba L., Coffea arabica L. and Prunus cerasus L., the remaining N uptake
      occurred via another pathway with an estimated average pore radius (r(P)) greater
      than 20 nm. This is two orders of magnitude greater than previous estimations of
      cuticular r(P), indicating that this pathway, which was only found in stomatous
      leaf surfaces, was probably not located in the cuticle but at the surfaces of the
      stomatal pores. In astomatous leaf surfaces of C. arabica and Populus x
      canadensis Moench, average r(P) was 2.0 and 2.4 nm, respectively, which is four
      to eight times larger than previous estimations of cuticular r(P). These results
      indicate that for polar solutes, the size exclusion limits of plant surfaces can
      be considerably larger than previously estimated. The far-reaching implications
      of these findings are discussed.

PMID- 18334003
TI  - Ultrastructural localization of acid phosphatase in arbusculate coils of
      mycorrhizal Phoenix canariensis roots.
AB  - Acid phosphatase (ACP) activity has been detected in roots of mycorrhizal and non
      mycorrhizal Phoenix canariensis. This enzyme was ultrastructurally localized in
      arbusculate coils for the first time. This localization was carried out using a
      cerium-based method, which minimizes non-specific precipitation. The ACP was
      localized in inter- and intracellular hyphae, in the fungal cytoplasm as well as
      at the interface and the fungal cell wall and the periarbuscular membrane
      limiting it. The novel localization of an ACP in the arbuscular mycorrhizal (AM)
      interface of arbusculate coils suggests that this enzyme may be involved in the
      phosphorus efflux from the mycorrhizal fungus to the host. The results presented
      in this article indicate that the role played by ACP in AM symbiosis may be more
      important than was previously thought and that arbusculate coils are highly
      relevant when considering nutrient transfer through AM symbiosis.

PMID- 18334004
TI  - Carbon monoxide-induced stomatal closure in Vicia faba is dependent on nitric
      oxide synthesis.
AB  - Recently, in animals, carbon monoxide (CO), like nitric oxide (NO), was
      implicated as another important physiological messenger or bioactive molecule.
      Previous researches indicate that heme oxygenase (HO)-1 (EC 1.14.99.3) catalyzes
      the oxidative conversion of heme to CO and biliverdin IXa (BV) with the
      concomitant release of iron. However, little is known about the physiological
      roles of CO in plant, especially in stomatal movement of guard cells. In the
      present paper, the regulatory role of CO during stomatal movement in Vicia faba
      was surveyed. Results indicated that, like sodium nitroprusside (SNP), CO donor
      hematin induced stomatal closure in dose- and time-dependent manners. These
      responses were also proved by the addition of gaseous CO aqueous solution with
      different concentrations, showing for the first time that CO and NO exhibit
      similar regulation role in the stomatal movement. Moreover, our data showed that
      2,4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO)/N(G)
      nitro-L-arginine-methyl ester (L-NAME) not only reversed stomatal closure by CO,
      but also suppressed the NO fluorescence induced by CO, implying that CO-induced
      stomatal closure probably involves NO/nitric oxide synthase (NOS) signal system.
      Additionally, the CO/NO scavenger hemoglobin (Hb) and CO-specific synthetic
      inhibitor zinc protoporphyrin IX (ZnPPIX), NO scavenger cPTIO and NOS inhibitor L
      NAME reversed the darkness-induced stomatal closure and NO fluorescence. These
      results show that, maybe like NO, the levels of CO in guard cells of V. faba is
      higher in dark than that in light, HO-1 and NOS are the enzyme systems
      responsible for generating endogenous CO and NO in darkness, respectively, and
      that CO being from HO-1 mediates darkness-induced NO synthesis in guard cells'
      stomatal closure of V. faba.

PMID- 18334005
TI  - Characterization of genes controlling stamen identity and development in a
      parthenocarpic tomato mutant indicates a role for the DEFICIENS ortholog in the
      control of fruit set.
AB  - The development of the ovary into a fruit depends on pollination and
      fertilization. It has been proposed that the restriction of ovary growth before
      pollination is because of the stamens acting as negative regulators. Accordingly,
      the silencing of genes responsible for stamen identity has been correlated with
      parthenocarpy in different species. The tomato (Solanum lycopersicum L.)
      parthenocarpic fruit (pat) mutation associates autonomous ovary development with
      homeotic transformation of the anthers and aberrancy of ovules in the ovary. In
      this study, we tested the hypothesis that stamen aberrations and parthenocarpy in
      pat are driven by cues coming from the altered expression of class B MADS box
      genes. The data showed that the Pat locus is not allelic to either of the two
      tomato mutations putatively involved in the B function, stamenless (sl)-2 and
      pistillate (pi) or to genes encoding class B transcription factors. Whereas pat
      pi double mutants were not recovered because of tight linkage, pat sl-2 double
      mutants showed mainly epistatic effects. The developmental regulation of the Sl
      DEFICIENS (DEF) gene in the wild-type (WT) at anthesis as well as its
      differential transcription in the pat ovary suggest that it plays a role in the
      control of ovary growth. Accordingly, when compared with the WT, the gene was
      also differentially expressed in the parthenocarpic fruit-2 (pat-2) mutant, that
      is not allelic to pat and has normal ovule development. Altogether the results
      indicate that in tomato SlDEF plays a role in the control of ovary growth and
      that the pat mutation is located upstream of this regulatory cascade.

PMID- 18334006
TI  - P53 and bcl-2 assessment in serous ovarian carcinoma.
AB  - The study objective was to determine the prognostic value of assessment of
      staining of p53 and bcl-2 in a well-selected group of serous ovarian carcinomas.
      Immunohistochemical detection was used to identify both p53 and bcl-2 positive
      tumors. One hundred thirty-two tumors were analyzed for positivity of staining,
      grade of staining intensity, and for p53 alone, percent expression rates. These
      were analyzed alongside traditional clinicopathologic parameters for their
      ability to predict overall survival (OS), disease-free survival (DFS), and
      response to chemotherapy (CR). Univariate COX analysis revealed percent p53
      expression (P = 0.012) and p53 grade (P = 0.01) to be significant predictors of
      DFS. Neither the p53 nor bcl-2 measurement parameters were found significant for
      OS or prediction of CR. On multivariate analysis, incorporating clinicopathologic
      parameters, p53 parameters did not retain independent significance for any
      outcome measure. As in primary reported studies, bcl-2 was not found to be of
      clear independent prognostic value in this group of ovarian tumors. If mutation
      of p53 and its consequent overexpression is an early event in ovarian
      tumorigenesis, then p53 assessment may prove useful prognostically in the
      assessment of either low-grade ovarian carcinomas, as a possible indicator for
      progression, or in early-stage ovarian tumors, as a marker of tumor aggression or
      likelihood of recurrence. p53 analysis of a larger group of stage I ovarian
      tumors would be desirable to further explain the potential association with DFS.

PMID- 18334007
TI  - A phase II, multicenter trial of weekly topotecan in patients with recurrent
      platinum-sensitive epithelial cancers of the ovary and peritoneum.
AB  - The purpose of this study was to evaluate the response rate and toxicity of
      weekly topotecan in patients with recurrent platinum-sensitive epithelial cancers
      of the ovary and peritoneum. Thirty-nine platinum-sensitive recurrent ovarian
      cancer patients received topotecan (4 mg/m(2)) intravenously day 1, day 8, day
      15, every 28 days. Colony-stimulating factors were excluded from the study.
      Clinical response was assessed by clinical, serologic, and radiographic measures
      at the conclusion of cycle four. Patients received 136 cycles of topotecan
      (median = 3; range 1-6) and were evaluated for response and toxicity. Median
      number of prior regimens was one. Grade 3/4 neutropenia developed in 3 (7.7%)
      patients. Grade 3 thrombocytopenia was seen in one (2.6%) patient, with no
      incidence of grade 4 thrombocytopenia. There was no evidence of grade 3 anemia,
      but one patient (2.6%) was associated with grade 4 anemia. There was no grade 3
      or 4 neuropathy. We encountered 18 dose reductions following less than or equal
      to grade 2 myelosuppression, necessitating the removal of eight (20.5%) patients
      prior to cycle four. Twenty-one (53.8%) patients were removed from the study due
      to disease progression. Following the completion of cycle four, four (10.3%)
      patients demonstrated stable disease and four (10.3%) patients exhibited a
      partial response. There were no complete responses. Median disease-free survival
      was 12 weeks. Weekly topotecan (4 mg/m(2)) demonstrated modest activity and was
      moderately well tolerated. However, the significant number of dose reductions and
      high incidence of patients who demonstrated disease progression suggests
      additional modifications with this specific regimen are necessary.

PMID- 18334008
TI  - The incidence of pelvic lymph node metastasis by FIGO staging for patients with
      adequately surgically staged endometrial adenocarcinoma of endometrioid
      histology.
AB  - The seminal Gynecologic Oncology Group study on surgical pathologic spread
      patterns of endometrial cancer demonstrated the risk of pelvic lymph node
      metastasis for clinical stage I endometrial cancer based on tumor grade and
      thirds of myometrial invasion. However, the FIGO staging system assigns surgical
      stage by categorizing depth of myometrial invasion in halves. The objective of
      this study was to determine the incidence of pelvic lymph node metastasis in
      endometrial cancer based on tumor grade and myometrial invasion as per the
      current FIGO staging system. We reviewed the records of all patients who
      underwent primary surgical staging for clinical stage I endometrial cancer at our
      institution between May 1993 and November 2005. To make the study cohort as
      homogeneous as possible, we included only cases of endometrioid histology. We
      also included only patients who had adequate staging, which was defined as a
      total hysterectomy with removal of at least eight pelvic lymph nodes. During the
      study period, 1036 patients underwent primary surgery for endometrial cancer. The
      study cohort was composed of the 349 patients who met study inclusion criteria.
      Distribution of tumor grade was as follows: grade 1, 80 (23%); grade 2, 182
      (52%); and grade 3, 87 (25%). Overall, 30 patients (9%) had pelvic lymph node
      metastasis. The incidence of pelvic lymph node metastasis in relation to tumor
      grade and depth of myometrial invasion (none, inner half, and outer half) was as
      follows: grade 1-0%, 0%, and 0%, respectively; grade 2-4%, 10%, and 17%,
      respectively; and grade 3-0%, 7%, and 28%, respectively. We determined the
      incidence of pelvic nodal metastasis in a large cohort of endometrial cancer
      patients of uniform histologic subtype in relation to tumor grade and a one-half
      myometrial invasion cutoff. These data are more applicable to current surgical
      practice than the previously described one-third myometrial invasion cutoff
      results.

PMID- 18334009
TI  - A cost comparison of two strategies for treating stage IB2 cervical cancer.
AB  - Patients with stage IB2 cervical cancer at our institution are treated primarily
      with definitive chemoradiation, or chemoradiation followed by adjuvant
      hysterectomy. We sought to compare the cost differences associated with these two
      strategies. We identified all patients with stage IB2 cervical cancer who
      received their entire treatment regimen at our institution between 1995 and 2004.
      All patients received a combination of chemotherapy, external beam radiation, and
      one brachytherapy procedure, followed by either a second brachytherapy procedure
      or a simple hysterectomy. We retrieved cost data associated with hospitalization
      for the completion of respective treatment, including pharmacy, laboratory and
      pathology, radiation, and operating room services, as well as the costs of
      supplies and room and board. We identified 46 patients with stage IB2 cervical
      cancer, 23 who received a second brachytherapy procedure and 23 who underwent
      simple hysterectomy. Patients displayed similar demographics and similar disease
      characteristics including initial tumor diameter and histology. The cost of care
      for adjuvant hysterectomy group was greater ($8,316.70 vs 5,508.70, P < 0.0001).
      Specific differences included higher operating room costs ($1520 vs 414, P <
      0.0001), pharmacy costs ($675 vs 342, P < 0.0001), and laboratory/pathology costs
      ($597 vs 89, P < 0.0001). We conclude that definitive chemoradiation appears to
      be associated with lower costs for management of stage IB2 cervical cancer when
      compared to simple adjuvant hysterectomy.

PMID- 18334010
TI  - Prognostic factors in women 45 years of age or younger with endometrial cancer.
AB  - The purpose of this study was to conduct a clinical and pathologic review of
      endometrial cancers diagnosed in women aged younger than 45 years to better
      identify the prognostic factors for this subgroup of women. We retrospectively
      evaluated the clinical history, treatment, and follow-up of patients with
      histologically confirmed endometrial cancer treated in Faculty Hospital Nitra,
      Slovakia from 1993 to 2003. Data were abstracted regarding tumor histology,
      grade, age, parity, stage, diabetes, use of oral contraceptives, body mass index
      (BMI), and survival. One hundred seventy-three patients with endometrioid
      histology were divided into two groups: younger group (age <or=45 years, n = 20)
      and older group (age >45, n = 153). Patients with high-risk histology (clear cell
      or serous papillary) were excluded from the study. Twenty patients less than or
      equal to 45 years of age received treatment for endometrial cancer: stage I, 16
      (80%); stage II, 2 (10%); stage III, 1 (5%); and stage IV, 1 (5%). Tumors were
      well differentiated in 12 (60%), moderately differentiated in 6 (30%), and poorly
      differentiated in 2 (10%). Age ranged from 28 to 45 years (mean 37), with mean
      BMI 35.8 +/- 9.4. At the end of study period, 17 (85%) were alive with no
      evidence of disease and 3 (15%) had died of recurrent disease. We conclude that
      patients less than or equal to 45 years of age have better survival compared to
      older patients. Deeper myometrial invasion was significantly associated with age
      greater than 45 years. Majority of young patients with endometrial cancer were
      obese and nulliparous.

PMID- 18334012
TI  - Characterization of a newly established uterine carcinosarcoma cell line
      featuring the sarcomatous phenotype of the tumor in vitro.
AB  - We describe the newly established cell line CS-99 derived from a uterine
      carcinosarcoma retaining features of the sarcomatous phenotype in vitro. CS-99
      cells exhibit a mesenchymal morphology with predominantly spindle-shaped cells at
      nonconfluence turning to pleomorphic appearance at confluence. The mesenchymal
      phenotype was evidenced immunohistochemically by strong vimentin and moderate SM
      actin, which was similar to the sarcomatous component of the primary tumor. P53
      was overexpressed in a subset of CS-99 cells. Epithelial membrane antigen was
      moderately expressed whereas other markers including pan CK, CK 5/6, CK 34,
      epidermal growth factor receptor, desmin, carcinoembryonic antigen, S100, KIT,
      ERBB2, and the hormone receptors, estrogen receptor and progesterone receptor
      revealed either weak or no specific staining in CS-99 cells. High self-renewal
      capacity corresponded to the population doubling time of 23 h in high passage. CS
      99 cells were able to develop three-dimensional tumor spheroids in vitro.
      Cytogenetic analysis and multicolor fluorescence in situ hybridization of CS-99
      demonstrated an almost stable karyotype including numerical changes +8, +18, and
      +20 and translocations, amongst others der(1)t(1;2), der(1)t(1;7), der(2)t(2;19),
      der(5)t(5;8), and der(5)t(5;14). Taken together, the cell line CS-99 exhibits
      strong growths dynamics and a complex but stable karyotype in higher passages,
      and can be further a useful in vitro model system for studying tumor biology of
      carcinosarcomas.

PMID- 18334011
TI  - Primary chemoprevention of endometrial hyperplasia with the peroxisome
      proliferator-activated receptor gamma agonist rosiglitazone in the PTEN
      heterozygote murine model.
AB  - PTEN mutations have been implicated in the development of endometrial hyperplasia
      and subsequent cancer. Peroxisome proliferator-activated receptor gamma (PPAR
      gamma) agonists have demonstrated antineoplastic and chemopreventive effects. The
      purpose of this study was to evaluate the effects of the PPAR-gamma agonist
      rosiglitazone on both PTEN wild type and PTEN null cell lines and in the PTEN
      heterozygote((+/-)) murine model. Hec-1-A (PTEN wild type) and Ishikawa (PTEN
      null) cells were treated with rosiglitazone. Thirty-five female PTEN(+/-) mice
      were genotyped and placed into one of four groups for treatment for 18 weeks: A)
      PTEN wild type with 4 mg/kg rosiglitazone, B) PTEN(+/-) mice with vehicle, C)
      PTEN(+/-) mice with 4 mg/kg rosiglitazone, and D) PTEN(+/-) mice with 8 mg/kg
      rosiglitazone. Proliferation and apoptosis were measured by bromodeoxyuridine
      (BrdU) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end
      labeling of DNA fragmentation sites assay. Rosiglitazone caused cell growth
      inhibition in both Hec-1-A and Ishikawa in a dose-dependent manner (P < 0.02 and
      P < 0.03, respectively). Rosiglitazone also induced apoptosis in both Hec-1-A (P
      < .001) and Ishikawa (P < .001) cells in a dose-dependent manner. In the murine
      model, rosiglitazone decreased proliferation of the endometrial hyperplastic
      lesions (B vs C; 39.7% vs 9.3% and B vs D; 39.7% vs 4.2%; P < 0.0001) and
      increased apoptosis of glandular endometrial epithelial cells (B vs C; 2.8% vs
      22.4%; P < 0.0001 and B vs D; 2.8% vs 30.2%; P = 0.003). PPAR-gamma agonist
      rosiglitazone inhibits proliferation and induces apoptosis in both PTEN intact
      and PTEN null cancer cell lines and in hyperplastic endometrial lesions in the
      PTEN(+/)(-)murine model.

PMID- 18334013
TI  - The risk of developing uterine sarcoma after tamoxifen use.
AB  - The treatment of breast cancer with tamoxifen results in an increased risk of
      uterine cancer. The objective of this study was to evaluate the association
      between tamoxifen use and the risk of developing uterine sarcomas and endometrial
      carcinomas in a historical cohort of women diagnosed with breast cancer in 1987
      1988. The medical records of all women diagnosed in Israel with breast cancer in
      the years 1987-1988 were sought. Clinical data, including use of hormone therapy,
      were extracted from oncology records. In 2004, patient identifiers were linked to
      the Israel Cancer Registry database to identify all uterine cancers that occurred
      within 15 years of the diagnosis of breast cancer. The records for 1507 breast
      cancer cases (84%) were retrieved. Among these cases, 32 uterine malignancies
      were identified; 11 occurred prior to the diagnosis of breast cancer and 21
      occurred during the follow-up period. Eight hundred seventy-five women in the
      cohort had used tamoxifen (59%). There were 17 uterine cancers observed among the
      875 exposed to tamoxifen (1.9%), compared to 4 uterine cancers among the 621
      women (0.6%) who did not use tamoxifen (odds ratio = 3.1; 95% CI: 1.0-9.1; P =
      0.04). There were four uterine sarcomas among the tamoxifen users, but none among
      nonusers (P = 0.15). Five of the 875 tamoxifen users (0.6%) died of uterine
      cancer, compared to no deaths among nonusers (P = 0.08). We conclude that in this
      national breast cancer cohort, tamoxifen use was associated with elevated risks
      of uterine cancer incidence and mortality. Uterine sarcomas appear to be
      overrepresented among women who use tamoxifen.

PMID- 18334014
TI  - Role of diaphragmatic surgery in 69 patients with ovarian carcinoma.
AB  - Diaphragmatic stripping or coagulation is a technique aiming to optimally
      cytoreduce ovarian cancer. We investigated the complications, the overall
      survival, and the relapse rate following this procedure. Records of 69 patients
      with diaphragmatic involvement who underwent debulking surgery between September
      1993 and December 2001 were reviewed. A total of 69 patients underwent
      diaphragmatic surgery as part of cytoreductive surgery for epithelial ovarian
      cancer. In 17 cases, the diaphragmatic tumors were stripped from the muscle, in
      22 cases coagulated, and in 30 cases stripped and coagulated. Postoperative
      complications were pleural effusion (41 cases, 3 needed a chest drain, 7 needed a
      pleural puncture, 1 needed both) and pneumothorax (4 cases, 1 needed a chest
      drain). In one case of bilateral pleural effusion, the patient developed
      pneumonia. In one case of pleural effusion on the right side, the patient needed
      a pleural puncture and developed a partial atelectasis of the middle lobe of the
      right lung. The median overall survival was 66 months in the stripping group
      compared with 49 months in the coagulation group. In 56 cases (81%), the patient
      developed a relapse, and the first site of relapse was the diaphragm in 11 cases
      (20%). We conclude that diaphragmatic resection is an important part of optimal
      debulking surgery with an acceptable morbidity.

PMID- 18334015
TI  - Cystic struma ovarii presenting as pseudo-Meigs' syndrome with elevated CA125
      levels. A case report and review of the literature.
AB  - Struma ovarii is a rare ovarian teratoma consisted predominantly of mature
      thyroid tissue. Although the vast majority of strumas are benign, they can
      present mimicking malignancy. We report a case of a postmenopausal woman who
      presented with a large pelvic mass, ascites, and high CA125 levels. Further
      investigation confirmed the existence of bilateral pleural effusions. The patient
      underwent laparotomy, and histology revealed a benign struma ovarii. Twelve
      months after the removal of the tumor, the patient remained disease free, with no
      clinical or radiologic evidence of effusion, and normal CA125 levels. This is
      only the fifth case in the English literature of a benign struma ovarii
      presenting as pseudo-Meigs' syndrome with elevated CA125. Struma ovarii should be
      included in the differential diagnosis of a pelvic mass that presents with
      ascites, hydrothorax, and elevated tumor markers.

PMID- 18334016
TI  - Treatment of aggressive angiomyxoma with aromatase inhibitor prior to surgical
      resection.
AB  - Aggressive angiomyxoma (AA) is a rare, locally infiltrating soft tissue tumor
      typically located in the genital tract of young, reproductive age women. Surgical
      excision has been the mainstay of treatment. Recently, gonadotropin-releasing
      hormone agonist therapy has been reported to decrease the size of estrogen
      receptor positive AA. We present the first case of a postmenopausal woman treated
      with an aromatase inhibitor to shrink the size of tumor prior to surgical
      resection.

PMID- 18334017
TI  - Careful adjustment of Epo non-viral gene therapy for beta-thalassemic anaemia
      treatment.
AB  - BACKGROUND: In situ production of a secreted therapeutic protein is one of the
      major gene therapy applications. Nevertheless, the plasmatic secretion peak of
      transgenic protein may be deleterious in many gene therapy applications including
      Epo gene therapy. Epo gene transfer appears to be a promising alternative to
      recombinant Epo therapy for severe anaemia treatment despite polycythemia was
      reached in many previous studies. Therefore, an accurate level of transgene
      expression is required for Epo application safety. The aim of this study was to
      adapt posology and administration schedule of a chosen therapeutic gene to avoid
      this potentially toxic plasmatic peak and maintain treatment efficiency. The
      therapeutic potential of repeated muscular electrotransfer of light Epo-plasmid
      doses was evaluated for anaemia treatment in beta-thalassemic mice. METHODS:
      Muscular electrotransfer of 1 microg, 1.5 microg, 2 microg, 4 microg or 6 microg
      of Epo-plasmid was performed in beta-thalassemic mice. Electrotransfer was
      repeated first after 3.5 or 5 weeks first as a initiating dose and then according
      to hematocrit evolution. RESULTS: Muscular electrotransfer of the 1.5 microg Epo
      plasmid dose repeated first after 5 weeks and then every 3 months was sufficient
      to restore a subnormal hematrocrit in beta-thalassemic mice for more than 9
      months. CONCLUSION: This strategy led to efficient, long-lasting and non-toxic
      treatment of beta-thalassemic mouse anaemia avoiding the deleterious initial
      hematocrit peak and maintaining a normal hematocrit with small fluctuation
      amplitude. This repeat delivery protocol of light doses of therapeutic gene could
      be applied to a wide variety of candidate genes as it leads to therapeutic effect
      reiterations and increases safety by allowing careful therapeutic adjustments.

PMID- 18334018
TI  - Isolation of soybean protein P34 from oil bodies using hydrophobic interaction
      chromatography.
AB  - BACKGROUND: Soybeans play a prominent role in allergologic research due to the
      high incidence of allergic reactions. For detailed studies on specific proteins
      it is necessary to have access to a large amount of pure substance. RESULTS: In
      this contribution, a method for purifying soybean (Glycine max) protein P34 (also
      called Gly m Bd 30 K or Gly m 1) using hydrophobic interaction chromatography is
      presented. After screening experiments using 1 mL HiTrap columns, Butyl Sepharose
      4 FF was selected for further systematic investigations. With this stationary
      phase, suitable operation conditions for two-step gradient elution using ammonium
      sulphate were determined experimentally. The separation conditions obtained in a
      small column could be scaled up successfully to column volumes of 7.5 and 75 mL,
      allowing for high product purities of almost 100% with a yield of 27% for the
      chromatographic separation step. Conditions could be simplified further using a
      onestep gradient, which gave comparable purification in a shorter process time.
      The identity of the purified protein was verified using in-gel digestion and mass
      spectrometry as well as immunological techniques. CONCLUSION: With the technique
      presented it is possible to produce, within a short timeframe, pure P34, suitable
      for further studies where an example antigen is needed.

PMID- 18334019
TI  - Exposure to diesel exhaust induces changes in EEG in human volunteers.
AB  - BACKGROUND: Ambient particulate matter and nanoparticles have been shown to
      translocate to the brain, and potentially influence the central nervous system.
      No data are available whether this may lead to functional changes in the brain.
      METHODS: We exposed 10 human volunteers to dilute diesel exhaust (DE, 300 mug/m3)
      as a model for ambient PM exposure and filtered air for one hour using a double
      blind randomized crossover design. Brain activity was monitored during and for
      one hour following each exposure using quantitative electroencephalography (QEEG)
      at 8 different sites on the scalp. The frequency spectrum of the EEG signals was
      used to calculate the median power frequency (MPF) and specific frequency bands
      of the QEEG. RESULTS: Our data demonstrate a significant increase in MPF in
      response to DE in the frontal cortex within 30 min into exposure. The increase in
      MPF is primarily caused by an increase in fast wave activity (beta2) and
      continues to rise during the 1 hour post-exposure interval. CONCLUSION: This
      study is the first to show a functional effect of DE exposure in the human brain,
      indicating a general cortical stress response. Further studies are required to
      determine whether this effect is mediated by the nanoparticles in DE and to
      define the precise pathways involved.

PMID- 18334020
TI  - The first case report of dental floss pick-related injury presenting with massive
      hemoptysis: a case report.
AB  - INTRODUCTION: A tracheobronchial foreign body is a rarely mentioned cause of
      massive hemoptysis. Although an aspirated toothpick is a well-known cause of
      traumatic injury to the respiratory tract, a similar device called a dental floss
      pick, which is much larger than a toothpick, has never been described as a
      tracheobronchial foreign body. CASE PRESENTATION: We report a case of massive
      hemoptysis in a 32-year-old man due to a dental floss pick in the left main
      bronchus. Flexible fiberoptic bronchoscopy was successful in removing the foreign
      body. CONCLUSION: Tracheobronchial foreign body can be a medical emergency
      requiring immediate intervention and massive hemoptysis may be the presenting
      symptom. Flexible fiberoptic bronchoscopy is recommended as the first-line
      treatment modality for tracheobronchial foreign body removal. A dental floss pick
      may present as a tracheobronchial foreign body and can reside in the airway
      asymptomatically for many years.

PMID- 18334021
TI  - Editor's note: new facial nerve section and new editorial board member.

PMID- 18334023
TI  - Quantification of specific bindings of biomolecules by magnetorelaxometry.
AB  - The binding reaction of the biomolecules streptavidin and anti-biotin antibody,
      both labelled by magnetic nanoparticles (MNP), to biotin coated on agarose beads,
      was quantified by magnetorelaxometry (MRX). Highly sensitive SQUID-based MRX
      revealed the immobilization of the MNP caused by the biotin-streptavidin
      coupling. We found that about 85% of streptavidin-functionalised MNP bound
      specifically to biotin-agarose beads. On the other hand only 20% of antibiotin
      antibody functionalised MNP were specifically bound. Variation of the suspension
      medium revealed in comparison to phosphate buffer with 0.1% bovine serum albumin
      a slight change of the binding behaviour in human serum, probably due to the
      presence of functioning (non heated) serum proteins. Furthermore, in human serum
      an additional non-specific binding occurs, being independent from the serum
      protein functionality.The presented homogeneous bead based assay is applicable in
      simple, uncoated vials and it enables the assessment of the binding kinetics in a
      volume without liquid flow. The estimated association rate constant for the MNP
      labelled streptavidin is by about two orders of magnitude smaller than the value
      reported for free streptavidin. This is probably due to the relatively large size
      of the magnetic markers which reduces the diffusion of streptavidin. Furthermore,
      long time non-exponential kinetics were observed and interpreted as agglutination
      of the agarose beads.

PMID- 18334022
TI  - Xylitol-supplemented nutrition enhances bacterial killing and prolongs survival
      of rats in experimental pneumococcal sepsis.
AB  - BACKGROUND: Xylitol has antiadhesive effects on Streptococcus pneumoniae and
      inhibits its growth, and has also been found to be effective in preventing acute
      otitis media and has been used in intensive care as a valuable source of energy.
      RESULTS: We evaluated the oxidative burst of neutrophils in rats fed with and
      without xylitol. The mean increase in the percentage of activated neutrophils
      from the baseline was higher in the xylitol-exposed group than in the control
      group (58.1% vs 51.4%, P = 0.03 for the difference) and the mean induced increase
      in the median strength of the burst per neutrophil was similarly higher in the
      xylitol group (159.6 vs 140.3, P = 0.04). In two pneumococcal sepsis experiments
      rats were fed either a basal powder diet (control group) or the same diet
      supplemented with 10% or 20% xylitol and infected with an intraperitoneal
      inoculation of S. pneumoniae after two weeks. The mean survival time was 48 hours
      in the xylitol groups and 34 hours in the control groups (P < 0.001 in log rank
      test). CONCLUSION: Xylitol has beneficial effects on both the oxidative killing
      of bacteria in neutrophilic leucocytes and on the survival of rats with
      experimental pneumococcal sepsis.

PMID- 18334024
TI  - Mannose-binding lectin deficiency is associated with early onset of polyarticular
      juvenile rheumatoid arthritis: a cohort study.
AB  - BACKGROUND: Mannose-binding lectin (MBL) is an innate immune protein. The aim of
      our study was to determine whether genetically determined MBL deficiency is
      associated with susceptibility to juvenile rheumatoid arthritis (JRA) and whether
      MBL2 genotypes are associated with JRA severity. METHODS: In a retrospective
      cohort study of 218 patients with polyarthritis (n = 67) and oligoarthritis (n =
      151), clinical and laboratory disease variables were obtained by clinical
      examination and chart reviews. Healthy Caucasian adults (n = 194) served as
      control individuals. MBL2 gene mutations were determined by Taqman analysis to
      identify genotypes with high, medium and low expression of MBL. Functional MBL
      plasma concentrations were measured using enzyme-linked immunosorbent assay.
      Associations between clinical and laboratory variables and MBL2 genotypes were
      determined by Kruskal-Wallis and chi2 tests. RESULTS: MBL2 genotype frequencies
      were similar in polyarthritis and oligoarthritis patients as compared with
      control individuals. MBL plasma concentrations were associated with the high,
      medium and low MBL genotype expression groups (P < 0.01). In polyarthritis
      patients, the presence of low-expressing (deficient) MBL2 genotypes was
      associated with early age at onset of disease (P = 0.03). In oligoarthritis
      patients, patients with low-expressing MBL2 genotypes were more often in
      remission (81%) than patients in the medium (54%) and high (56%) genotype groups
      (P = 0.02). The remaining clinical and laboratory variables, such as arthritis
      severity index, presence of radiographic erosions and antinuclear antibody
      positivity, were not associated with MBL2 genotypes. CONCLUSION: Genetically
      determined MBL deficiency does not increase susceptibility to JRA, but MBL
      deficiency is associated with a younger age at onset of juvenile polyarthritis.
      On the other hand, MBL-deficient children with juvenile oligoarthritis are more
      often in remission. Therefore, MBL appears to play a dual role in JRA.

PMID- 18334025
TI  - Systems biology-defined NF-kappaB regulons, interacting signal pathways and
      networks are implicated in the malignant phenotype of head and neck cancer cell
      lines differing in p53 status.
AB  - BACKGROUND: Aberrant activation of the nuclear factor kappaB (NF-kappaB) pathway
      has been previously implicated as a crucial signal promoting tumorigenesis.
      However, how NF-kappaB acts as a key regulatory node to modulate global gene
      expression, and contributes to the malignant heterogeneity of head and neck
      cancer, is not well understood. RESULTS: To address this question, we used a
      newly developed computational strategy, COGRIM (Clustering Of Gene Regulons using
      Integrated Modeling), to identify NF-kappaB regulons (a set of genes under
      regulation of the same transcription factor) for 1,265 genes differentially
      expressed by head and neck cancer cell lines differing in p53 status. There were
      748 NF-kappaB targets predicted and individually annotated for RELA, NFkappaB1 or
      cREL regulation, and a prevalence of RELA related genes was observed in over
      expressed clusters in a tumor subset. Using Ingenuity Pathway Analysis, the NF
      kappaB targets were reverse-engineered into annotated signature networks and
      pathways, revealing relationships broadly altered in cancer lines (activated
      proinflammatory and down-regulated Wnt/beta-catenin and transforming growth
      factor-beta pathways), or specifically defective in cancer subsets (growth
      factors, cytokines, integrins, receptors and intermediate kinases).
      Representatives of predicted NF-kappaB target genes were experimentally validated
      through modulation by tumor necrosis factor-alpha or small interfering RNA for
      RELA or NFkappaB1. CONCLUSION: NF-kappaB globally regulates diverse gene programs
      that are organized in signal networks and pathways differing in cancer subsets
      with distinct p53 status. The concerted alterations in gene expression patterns
      reflect cross-talk among NF-kappaB and other pathways, which may provide a basis
      for molecular classifications and targeted therapeutics for heterogeneous subsets
      of head and neck or other cancers.

PMID- 18334027
TI  - Bilateral undisplaced insufficiency neck of femur fractures associated with short
      term steroid use: a case report.
AB  - INTRODUCTION: We present an interesting and unusual case of a 61-year-old woman
      with bilateral, undisplaced, stress neck of femur fractures associated with short
      term steroid use. Insufficiency fractures of the neck of femur without preceding
      trauma have been described in the literature, although bilateral involvement is
      infrequent. These fractures have been associated with strenuous exercise,
      seizures, renal osteodystrophy, fluoride treatment, long-term corticosteroid use,
      amenorrhoea, abnormal anatomy and osteomalacia due to nutritional and/or hormonal
      factors. CASE PRESENTATION: The case we present differs from other published
      reports, in that the patient's symptoms developed acutely after only a short
      course of steroids and with no associated trauma or strenuous exercise. It is
      also the only case described where no operative intervention was required.
      CONCLUSION: Our case reiterates the importance of considering insufficiency or
      stress fractures in high-risk patients who present with musculoskeletal pain.
      Institution of bone protection should also be considered in these patients.
      Morbidity related to delayed treatment has been well documented, so a high level
      of clinical suspicion is imperative.

PMID- 18334026
TI  - Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins
      in ancestral eukaryotes and discovery of a novel Hint motif.
AB  - BACKGROUND: The Hedgehog (Hh) signaling pathway plays important roles in human
      and animal development as well as in carcinogenesis. Hh molecules have been found
      in both protostomes and deuterostomes, but curiously the nematode Caenorhabditis
      elegans lacks a bona-fide Hh. Instead a series of Hh-related proteins are found,
      which share the Hint/Hog domain with Hh, but have distinct N-termini. RESULTS: We
      performed extensive genome searches such as the cnidarian Nematostella vectensis
      and several nematodes to gain further insights into Hh evolution. We found six
      genes in N. vectensis with a relationship to Hh: two Hh genes, one gene with a Hh
      N-terminal domain fused to a Willebrand factor type A domain (VWA), and three
      genes containing Hint/Hog domains with distinct novel N-termini. In the nematode
      Brugia malayi we find the same types of hh-related genes as in C. elegans. In the
      more distantly related Enoplea nematodes Xiphinema and Trichinella spiralis we
      find a bona-fide Hh. In addition, T. spiralis also has a quahog gene like C.
      elegans, and there are several additional hh-related genes, some of which have
      secreted N-terminal domains of only 15 to 25 residues. Examination of other Hh
      pathway components revealed that T. spiralis - like C. elegans - lacks some of
      these components. Extending our search to all eukaryotes, we recovered genes
      containing a Hog domain similar to Hh from many different groups of protists. In
      addition, we identified a novel Hint gene family present in many eukaryote groups
      that encodes a VWA domain fused to a distinct Hint domain we call Vint. Further
      members of a poorly characterized Hint family were also retrieved from bacteria.
      CONCLUSION: In Cnidaria and nematodes the evolution of hh genes occurred in
      parallel to the evolution of other genes that contain a Hog domain but have
      different N-termini. The fact that Hog genes comprising a secreted N-terminus and
      a Hog domain are found in many protists indicates that this gene family must have
      arisen in very early eukaryotic evolution, and gave rise eventually to hh and hh
      related genes in animals. The results indicate a hitherto unsuspected ability of
      Hog domain encoding genes to evolve new N-termini. In one instance in Cnidaria,
      the Hh N-terminal signaling domain is associated with a VWA domain and lacks a
      Hog domain, suggesting a modular mode of evolution also for the N-terminal
      domain. The Hog domain proteins, the inteins and VWA-Vint proteins are three
      families of Hint domain proteins that evolved in parallel in eukaryotes.

PMID- 18334028
TI  - Conditional clustering of temporal expression profiles.
AB  - BACKGROUND: Many microarray experiments produce temporal profiles in different
      biological conditions but common cluster techniques are not able to analyze the
      data conditional on the biological conditions. RESULTS: This article presents a
      novel technique to cluster data from time course microarray experiments performed
      across several experimental conditions. Our algorithm uses polynomial models to
      describe the gene expression patterns over time, a full Bayesian approach with
      proper conjugate priors to make the algorithm invariant to linear
      transformations, and an iterative procedure to identify genes that have a common
      temporal expression profile across two or more experimental conditions, and genes
      that have a unique temporal profile in a specific condition. CONCLUSION: We use
      simulated data to evaluate the effectiveness of this new algorithm in finding the
      correct number of clusters and in identifying genes with common and unique
      profiles. We also use the algorithm to characterize the response of human T cells
      to stimulations of antigen-receptor signaling gene expression temporal profiles
      measured in six different biological conditions and we identify common and unique
      genes. These studies suggest that the methodology proposed here is useful in
      identifying and distinguishing uniquely stimulated genes from commonly stimulated
      genes in response to variable stimuli. Software for using this clustering method
      is available from the project home page.

PMID- 18334029
TI  - Ethnophytotherapeutical research in the high Molise region (Central-Southern
      Italy).
AB  - BACKGROUND: In the years 2003-2005 research was carried out concerning ethno
      medicine in the high Molise (central- southern Italy), a region that has been the
      object of very little investigation from the ethnobotanical point of view. Upper
      Molise is a continuation of the mountain profiles of the Abruzzi Appenines: a
      series of hills, steep slopes and deep fluvial valleys making communications
      difficult. Primordial traditions (e.g. harvest feasts) are typical of the region.
      METHODS: Field data were collected through open interviews in the field. These
      were conducted on both an individual and group level, fresh plants gathered from
      surrounding areas being displayed. In other cases, individual interviews were
      conducted by accompanying the person involved to the places where they perform
      their activities (for example, in the woods with woodcutters, kitchen gardens and
      fields with housewives, pastures with shepherds, etc.). In total 54 individuals
      were interviewed. RESULTS: Data of 70 taxa belonging to 39 families were
      gathered. Among the species, 64 are used in human therapy, 5 as insect
      repellents, 11 in veterinary medicine, 1 to keep eggs and cheeses and 4 for magic
      purposes. The most important findings in ethno-medicine relate to the lichen
      Lobaria pulmonaria (L.) Hoffm. (wounds) and to some vascular plant species:
      Asplenium trichomanes L. and Ceterach officinarum Willd. (to regularize
      menstruation), Cyclamen hederifolium (chilblains), Centaurium erythraea Rafn. and
      Pulmonaria apennina Cristof. & Puppi (bruises), while in the ethno-veterinary
      field, we have Valeriana officinalis L. (wounds sustained by mules). Also worthy
      of note, given the isolation of the area, is the number of plants used to protect
      foodstuffs from parasites, among which Allium sativum L. and Capsicum frutescens
      L. CONCLUSION: The research revealed a deep-rooted and widespread habit of
      husbanding the family's resources. Whilst isolation and snowfalls contributed to
      the widespread knowledge of means of conserving foodstuffs, they also led to the
      use of products easily available within each home. The values of E.I.
      (ethnobotanicity index) for the upper Molise region are considered amongst the
      highest in Italian areas. Nevertheless, like the values for other areas of Italy,
      they are lower than those of many Spanish areas, perhaps (and not only) because
      of the more rapid cultural erosion experienced in Italy.

PMID- 18334030
TI  - Period-2: a tumor suppressor gene in breast cancer.
AB  - Previous reports have suggested that the ablation of the Period 2 gene (Per 2)
      leads to enhanced development of lymphoma and leukemia in mice. Employing
      immunoblot analyses, we have demonstrated that PER 2 is endogenously expressed in
      human breast epithelial cell lines but is not expressed or is expressed at
      significantly reduced level in human breast cancer cell lines. Expression of PER
      2 in MCF-7 breast cancer cells significantly inhibited the growth of MCF-7 human
      breast cancer cells, and, when PER 2 was co-expressed with the Crytochrome 2 (Cry
      2) gene, an even greater growth-inhibitory effect was observed. The inhibitory
      effect of PER 2 on breast cancer cells was also demonstrated by its suppression
      of the anchorage-independent growth of MCF-7 cells as evidenced by the reduced
      number and size of colonies. A corresponding blockade of MCF-7 cells in the G1
      phase of the cell cycle was also observed in response to the expression of PER 2
      alone or in combination with CRY 2. Expression of PER 2 also induced apoptosis of
      MCF-7 breast cancer cells as demonstrated by an increase in PARP [poly (ADP
      ribose) polymerase] cleavage. Finally, our studies demonstrate that PER 2
      expression in MCF-7 breast cancer cells is associated with a significant decrease
      in the expression of cyclin D1 and an up-regulation of p53 levels.

PMID- 18334031
TI  - Expression in Escherichia coli, purification, refolding and antifungal activity
      of an osmotin from Solanum nigrum.
AB  - BACKGROUND: Heterologous protein expression in microorganisms may contribute to
      identify and demonstrate antifungal activity of novel proteins. The Solanum
      nigrum osmotin-like protein (SnOLP) gene encodes a member of pathogenesis-related
      (PR) proteins, from the PR-5 sub-group, the last comprising several proteins with
      different functions, including antifungal activity. Based on deduced amino acid
      sequence of SnOLP, computer modeling produced a tertiary structure which is
      indicative of antifungal activity. RESULTS: To validate the potential antifungal
      activity of SnOLP, a hexahistidine-tagged mature SnOLP form was overexpressed in
      Escherichia coli M15 strain carried out by a pQE30 vector construction. The urea
      solubilized His6-tagged mature SnOLP protein was affinity-purified by immobilized
      metal (Ni2+) affinity column chromatography. As SnOLP requires the correct
      formation of eight disulfide bonds, not correctly formed in bacterial cells, we
      adapted an in vitro method to refold the E. coli expressed SnOLP by using
      reduced:oxidized gluthatione redox buffer. This method generated biologically
      active conformations of the recombinant mature SnOLP, which exerted antifungal
      action towards plant pathogenic fungi (Fusarium solani f. sp.glycines,
      Colletotrichum spp., Macrophomina phaseolina) and oomycete (Phytophthora
      nicotiana var. parasitica) under in vitro conditions. CONCLUSION: Since SnOLP
      displays activity against economically important plant pathogenic fungi and
      oomycete, it represents a novel PR-5 protein with promising utility for
      biotechnological applications.

PMID- 18334032
TI  - Plaque complement activation and cognitive loss in Alzheimer's disease.
AB  - BACKGROUND: Complement activation is increased in Alzheimer's disease (AD), but
      its significance is unclear. The objective of this study was to determine the
      relationship between complement activation and cognition during the development
      of AD. METHODS: iC3b, C9, Bielschowsky, and Gallyas staining was performed on
      aged normal (n = 17), mild cognitively impaired (n = 12), and AD (n = 17-18)
      inferior temporal gyrus specimens. Plaques were counted in 10x fields with high
      numbers of Bielschowsky-stained plaques. One-way ANOVA was used to determine
      between-group differences for plaque counts and measures of cognitive function,
      and linear regression was used to evaluate global cognition as a function of
      Bielschowsky-stained plaques. Terms for iC3b- and C9-stained plaques were then
      added sequentially as additional predictors in a "mediation analysis" model.
      RESULTS: Complement was detected on plaques in all groups, and on neurofibrillary
      tangles only in AD specimens. iC3b, C9, and Bielschowsky-stained plaque counts
      increased 2.5- to 3-fold in AD vs. other groups (all p < or = 0.01). C9 staining
      was present on some diffuse plaques, as well as on neuritic plaques. Bielschowsky
      stained and complement-stained plaque counts were highly correlated, and were
      negatively correlated with cognitive measures. When the Bielschowsky plaque count
      was used as a predictor, its correlations with cognitive measures were
      statistically significant, but when iC3b and C9 plaque counts were added as
      additional predictors, these correlations were no longer significant. This loss
      of significance was attributed to multicollinearity, i.e., high correlations
      between Bielschowsky-stained and complement-stained plaque counts. CONCLUSION:
      Both early-stage (iC3b) and late-stage (C9) complement activation occurs on
      neocortical plaques in subjects across the cognitive spectrum; contrary to
      previous reports, C9 is present on some diffuse plaques. Because of high
      correlations between complement-stained and Bielschowsky-stained plaque counts,
      quantitative assessment of the extent to which complement activation may mediate
      the relationship between plaques and cognitive function could not be performed.
      Additional studies with animal models of AD (if late-stage complement activation
      can be demonstrated), or possibly a trial in AD patients with an inhibitor of
      late-stage complement activation, may be necessary to determine the significance
      of this process in AD.

PMID- 18334034
TI  - Diversity: a key feature of public health nutrition research.

PMID- 18334035
TI  - Out of the box: why do we all now seem to agree that obesity is a disease; and
      what's wrong with being overweight?

PMID- 18334033
TI  - Transient T cell depletion causes regression of melanoma metastases.
AB  - BACKGROUND: Cognate immunity against neoplastic cells depends on a balance
      between effector T cells and regulatory T (Treg) cells. Treg cells prevent immune
      attack against normal and neoplastic cells by directly suppressing the activation
      of effector CD4+ and CD8+ T cells. We postulated that a recombinant interleukin
      2/diphtheria toxin conjugate (DAB/IL2; Denileukin Diftitox; Ontak) may serve as a
      useful strategy to deplete Treg cells and break tolerance against neoplastic
      tumors in humans. METHODS: We administered DAB/IL2 (12 microg/kg; four daily
      doses; 21 day cycles) to 16 patients with metastatic melanoma and measured the
      effects on the peripheral blood concentration of several T cell subsets and on
      tumor burden. RESULTS: We found that DAB/IL2 caused a transient depletion of Treg
      cells as well as total CD4+ and CD8+ T cells (< 21 days). T cell repopulation
      coincided with the de novo appearance of melanoma antigen-specific CD8+ T cells
      in several patients as determined by flow cytometry using tetrameric MART-1,
      tyrosinase and gp100 peptide/MHC conjugates. Sixteen patients received at least
      one cycle of DAB/IL2 and five of these patients experienced regressions of
      melanoma metastases as measured by CT and/or PET imaging. One patient experienced
      a near complete response with the regression of several hepatic and pulmonary
      metastases coupled to the de novo appearance of MART-1-specific CD8+ T cells. A
      single metastatic tumor remained in this patient and, after surgical resection,
      immunohistochemical analysis revealed MART1+ melanoma cells surrounded by CD8+ T
      cells. CONCLUSION: Taken together, these data indicate that transient depletion
      of T cells in cancer patients may disrupt the homeostatic control of cognate
      immunity and allow for the expansion of effector T cells with specificity against
      neoplastic cells. Several T cell depleting agents are clinically available and
      this study provides strong rationale for an examination of their efficacy in
      cancer patients. TRIAL REGISTRATION: NCT00299689 (ClinicalTrials.gov Identifier).

PMID- 18334036
TI  - 1-Microgram-cosyntropin test for the evaluation of adrenal insufficiency in
      critically ill surgical patients.

PMID- 18334037
TI  - Fatal outcome during anaesthesia induction in a patient with amiodarone-induced
      thyrotoxicosis.

PMID- 18334038
TI  - Thoracic epidural anaesthesia in valvular cardiac surgery.

PMID- 18334039
TI  - Acute upper airway obstruction due to displacement of a Sengstaken-Blakemore
      tube.

PMID- 18334040
TI  - The use of esmolol to treat systolic anterior motion of the mitral valve after
      mitral valve repair.

PMID- 18334041
TI  - Argatroban therapy in patients with hepatic and renal impairment.

PMID- 18334042
TI  - An unusual fatal reaction to a test dose of aprotinin before elective
      thoracoabdominal aortic aneurysm repair.

PMID- 18334043
TI  - The relationship between total plasma carotenoids and risk factors for chronic
      disease among middle-aged and older men.
AB  - Individual plasma carotenoids have been associated with various chronic diseases
      but little is known about the relationship between total plasma carotenoids and
      risk factors for chronic diseases. In the Physicians' Health Study, we examined
      492 men free of CVD and cancer for the relationship between total plasma
      carotenoids (the sum of alpha-carotene, beta-carotene, lycopene, zeaxanthin,
      lutein and beta-cryptoxanthin) and a wide variety of factors that predict chronic
      disease. Multivariate linear and logistic regression was performed to calculate
      parameter estimates (95% CI) and OR (95% CI) for total plasma carotenoids. In
      linear regression models, BMI, hypertension, alcohol intake and plasma levels of
      each lipid parameter and a-tocopherol significantly predicted levels of total
      plasma carotenoids. Upon adjustment for multiple chronic disease risk factors,
      the OR for levels of total plasma carotenoids greater than or equal to the median
      (> or=1.301 micromol/l) was statistically significant for current smoking (OR
      0.21; 95% CI 0.06, 0.77), weekly alcohol ingestion (OR 2.30; 95% CI 1.06, 4.99),
      daily alcohol ingestion (OR 2.46; 95% CI 1.29, 4.67), each 100 mg/l increase in
      total cholesterol (OR 0.73; 95% CI 0.58, 0.91), LDL-cholesterol (OR 1.48; 95% CI
      1.17, 1.89) and HDL-cholesterol (OR 1.58; 95% CI 1.26, 1.99), each 100 mg/ml
      increase in intercellular adhesion molecule-1 (OR 0.70; 95% CI 0.53, 0.93) and
      each 10 micromol/l increase in alpha-tocopherol (OR 1.33; 95% CI 1.12, 1.57),
      using logistic regression. Few lifestyle and clinical risk factors appear to be
      related to levels of total plasma carotenoids; however, levels of biomarkers such
      as plasma lipids and alpha-tocopherol may be strongly related.

PMID- 18334044
TI  - Contribution of gut microbial lysine to liver and milk amino acids in lactating
      does.
AB  - The contribution of microbial amino acids through caecotrophy to tissue protein
      metabolism was investigated in lactating does. Attempts were made to vary
      microbial supply through a dietary antibiotic, Zn bacitracin, and to vary tissue
      demand through manipulation of litter size. Three groups of eight New Zealand
      does were fed different experimental diets from day 28 of pregnancy to day 26 of
      lactation. The control group received the basal diet formulated to meet
      requirements with grass hay, wheat, soybean meal and barley grain. The second (no
      antibiotic) group and the third (bacitracin; BAC) group ingested the basal diet
      supplemented with ammonium sulfate (5 g/kg), initially unlabelled (day 1 to day
      8) then labelled with 15N (day 9 to day 30), while the BAC diet was also
      supplemented throughout with antibiotic (Zn bacitracin; 100 mg/kg). From just
      after birth each group of does was subdivided into two groups, each of four
      females, with the litter size either five (LS5) or nine (LS9) pups. The 15N
      enrichment in liver, milk and caecal bacteria amino acids was determined by GC
      combustion-isotope ratio MS. All amino acids in bacterial protein were enriched
      with the (15 NH 4)2SO4 treatment, with lysine 15N enrichment significantly
      greater in caecal bacteria (0.23 (SE 0.0063) atom % excess (ape)) than in liver
      (0.04 (SE 0.0004) ape) or milk protein (0.05 (SE 0.0018) ape), confirming the
      double origin (bacterial and dietary) of tissue lysine. The contribution of
      microbes to tissue lysine was 0.23 (SE 0.006) when milk protein was used as
      reference.

PMID- 18334045
TI  - Spatial constraints underlying the retinal mosaics of two types of horizontal
      cells in cat and macaque.
AB  - Most types of retinal neurons are spatially positioned in non-random patterns,
      termed retinal mosaics. Several developmental mechanisms are thought to be
      important in the formation of these mosaics. Most evidence to date suggests that
      homotypic constraints within a type of neuron are dominant, and that heterotypic
      interactions between different types of neuron are rare. In an analysis of
      macaque H1 and H2 horizontal cell mosaics, Wassle et al. (2000) suggested that
      the high regularity index of the combined H1 and H2 mosaic might be caused by
      heterotypic interactions during development. Here we use computer modeling to
      suggest that the high regularity index of the combined H1 and H2 mosaic is a by
      product of the basic constraint that two neurons cannot occupy the same space.
      The spatial arrangement of type A and type B horizontal cells in cat retina also
      follow this same principle.

PMID- 18334047
TI  - Make meal time a family affair.

PMID- 18334048
TI  - Dietitians' attitudes, perceptions, and usage patterns for fresh-cut fruit and
      vegetables.
AB  - PURPOSE: New fresh-cut fruit and vegetable products are being developed
      worldwide. Nutrition educators' perceptions of these products were studied.
      METHODS: Professional dietitians in Nova Scotia were asked to complete a
      questionnaire on their use of fresh-cut produce. The questionnaire also elicited
      their attitudes and perceptions about the convenience, taste/quality,
      nutrition/health benefits, cost, and safety of fresh-cut fruit and vegetables.
      RESULTS: Sixty-three percent of respondents reported eating five to six servings
      of fruit and vegetables a day. This group most frequently consumed fresh-cut
      fruit as snacks or dessert, and vegetables in stir-fry dishes or salads or cooked
      with meals. In general, fresh-cut fruit and vegetables were perceived as
      convenient, safe, and nutritious. While approximately 50% of participants felt
      fresh-cut produce did not differ in taste from whole fresh produce, almost the
      same number considered whole fresh produce superior in taste. CONCLUSIONS:
      Dietitians have a generally positive perception of fresh-cut products; however,
      there is uncertainty about the nutritional value, cost/benefit, and use of the
      products. Dietitians require more information on the nutrient value of these
      products and on suggested alternative uses. Attention should be paid to
      developing fresh-cut products that have good sensory quality.

PMID- 18334049
TI  - A review of family meal influence on adolescents' dietary intake.
AB  - Recent concerns about adolescent nutrition and unhealthy weights have prompted an
      examination of the myriad influences on dietary intake during adolescence.
      Included here are a summary of the literature on family influence on dietary
      intake, specifically during adolescence and within the family context, a summary
      of family meal patterns, and a systematic review of the known influences of
      family meals on dietary intake. Because of the complexity of families in today's
      society, models were developed to depict the broad context of familial influences
      on adolescent nutritional behaviours and attitudes and to describe what is known
      and not known about family meal influences on adolescent dietary intake and
      quality. A systematic review of the literature revealed seven articles
      specifically related to adolescents, family meals, and dietary intake, which were
      analyzed for strength of evidence and plausibility. In spite of data collection
      methods relying on self-report, results suggested that family meals were
      associated with improved dietary intakes. Families in today's societies are
      complex. Nevertheless, parents have the potential to influence positively,
      through family meals, what food is provided, where it is provided (e.g., home,
      restaurant), and within what type of atmosphere it is provided.

PMID- 18334050
TI  - Moderate weight loss: a self-directed protocol for women.
AB  - This innovative, self-directed diet and physical activity program was designed to
      achieve moderate weight loss in women. Thirty-five overweight or obese
      hyperlipidemic women completed a 20-week weight loss study. The weight loss
      intervention consisted of a 20% decrease in energy intake through diet and a 10%
      increase in energy expenditure through physical activity. The diet consisted of
      50-60% carbohydrates, 20% protein, and 20-30% fat. A personal trainer prescribed
      physical activity regimens. A progress-tracking system and monthly group sessions
      were used to maintain participant motivation throughout the weight loss period.
      Participants lost an average of 11.7 +/- 2.5 kg (p<0.001). The pattern of weight
      loss was linear (p<0.001) throughout the study period. Average weight loss per
      week was 0.59 +/- 0.55 kg. This 20-week program, combining a structured self
      selected diet and independent preplanned physical activity with motivational
      strategies, resulted in weight loss comparable to that observed in more
      controlled interventions. The lower cost, ease of use, and outcome success make
      this approach potentially useful in a clinical setting.

PMID- 18334051
TI  - Should long-term care residents be supplemented with vitamin D?
AB  - The Health Canada recommendation of 600 IU of vitamin D daily for those over age
      70 may be inadequate to prevent deficiencies. A literature search was conducted
      to examine whether older people living in long-term care (LTC) facilities are at
      high risk for vitamin D deficiency and therefore should receive a minimum daily
      supplement of 800 IU. The search included the major databases; the search terms
      "elderly" and "vitamin D" were used. Articles primarily related to calcium were
      excluded. The results show that North American seniors generally consume a diet
      low in vitamin D and have limited sun exposure. The majority, particularly those
      living in LTC facilities, may have a vitamin D deficiency. Also contributing to
      deficiencies is an age-related decline in cutaneous production of vitamin D and
      altered metabolic processes responsible for converting vitamin D to its active
      form. In summary, research conducted in both Canada and the United States
      provides sufficient evidence to indicate that older people living in LTC
      facilities are at high risk for vitamin D deficiency and should receive a minimum
      daily supplement of 800 IU.

PMID- 18334052
TI  - Gaining entry-level clinical competence outside of the acute care setting.
AB  - Traditionally, an emphasis has been placed on dietetic interns' attainment of
      entry-level clinical competence in acute care facilities. The perceived risks and
      benefits of acquiring entry-level clinical competence within long-term and acute
      care clinical environments were examined. The study included a purposive sample
      of recent graduates and dietitians (n=14) involved in an integrated internship
      program. Study subjects participated in in-depth individual interviews. Data were
      thematically analyzed with the support of data management software QSR N6.
      Perceived risks and benefits were associated with receiving clinical training
      exclusively in either environment; risks in one area surfaced as benefits in the
      other. Themes that emerged included philosophy of care, approach to practice,
      working environment, depth and breadth of experience, relationships (both client
      and professional), practice outcomes, employment opportunities, and attitude.
      Entry-level clinical competence is achievable in both acute and long-term care
      environments; however, attention must be paid to identified risks. Interns who
      consider gaining clinical competence exclusively in one area can reduce risks and
      better position themselves for employment in either practice area by
      incorporating an affiliation in the other area into their internship program.

PMID- 18334053
TI  - Evaluation of a nutrition education component nested in the NutriSTEP Project.
AB  - PURPOSE: Parents' health literacy skills include food and nutrition knowledge, as
      well as the ability to read, comprehend, and use information related to their
      children's health. The evaluation of a nutrition education booklet within the
      NutriSTEP (Nutrition Screening Tool for Every Preschooler) Project was conducted.
      Parents' nutrition education needs and their sources of nutrition information
      were also assessed. METHODS: Eight dietitians from four provinces conducted in
      person interviews with a sample of 322 parents. Parents were asked their
      perception of the booklet and reported learning. Dietitians' written feedback on
      the booklet and their recorded comments and nutrition advice to parents were
      gathered. RESULTS: Collated feedback led to significant revisions to the booklet.
      Parents reported increased knowledge from the booklet; 38% wanted more
      information on nutrition, while 25% wanted to know more about preschoolers and
      physical activity. The top three sources of nutrition advice for this parent
      sample were physicians, dietitians, and public health units. CONCLUSIONS: Written
      materials must be evaluated with the target audience to improve readability and
      comprehension. Further nutrition education efforts should be targeted through
      parents' main sources of nutrition information. Further research is needed on
      nutrition education intervention effectiveness to promote positive health
      outcomes.

PMID- 18334054
TI  - Sublingual immunotherapy for latex allergy: tolerability and safety profile of
      rush build-up phase.
AB  - OBJECTIVE: Sublingual immunotherapy represents an efficient therapeutic tool for
      the management of latex allergic patients. Local and systemic adverse reactions
      are reported, and risk factors for those reactions are poorly understood. The aim
      of this study is to compare two different rush induction protocols (2-day and 3
      day) in terms of safety and tolerability and effectiveness in reaching the
      maintenance dose. METHODS: Twenty-three outpatients (F/M = 18:5; 5-64 years of
      age), with latex allergy were randomly assigned to: Group 1 (2-day) and Group 2
      (3-day). Adverse reactions were classified by their type and severity. RESULTS:
      Twenty-one subjects, 10 from Group 1 and 11 from Group 2, reached the maintenance
      dose, 70% of them without side effects. Seven adverse events were reported in
      Group 1: three were local (oral itching) and spontaneously remitted; four were
      systemic (Grade-2: two reactions; Grade-3: two reactions) and were effectively
      controlled with drugs. The protocol was interrupted in two cases because of
      recurrent reactions. No reactions were reported in Group 2. Age, gender, atopy,
      specific IgE, skin prick tests and sublingual challenge did not seem to influence
      the risk of side effects significantly. No significant modification of skin tests
      and specific IgE levels were reported in both groups. The cutaneous test turned
      negative in 16 patients, eight from Group 1 (80%) and eight from Group 2 (73%).
      The remaining patients (two from Group 1 and three from Group 2) showed a
      reduction of latex reactivity, in terms of symptom score (MIS: 2 vs. 0.5 in Group
      1, 3 vs. 1 in Group 2). CONCLUSIONS: This study confirms the safety of rush
      induction. The 3-day protocol was better tolerated than the 2-day. Significant
      risk factors for the occurrence of adverse reactions were not identified. Only
      the type of protocol but not patient-related parameters seemed predictive of side
      effects.

PMID- 18334055
TI  - Empathy: improving the quality of the genitourinary medicine consultation.
AB  - The interaction between patient and practitioner remains core to the provision of
      medical care. Physicians who display a warm, friendly and reassuring manner
      during their consultations are reported to be more effective in their delivery of
      care, with empathy, in particular, emerging as a key factor. This paper examines
      the concept of empathy and discusses how this may be achieved, with particular
      emphasis on the genitourinary medicine consultation.

PMID- 18334056
TI  - Do all patients attending genitourinary medicine services want to be seen within
      48 hours?
AB  - At a time of high capacity almost 40% of patients declined an appointment within
      48 hours. Data were collected prospectively on the reasons why, and the impact of
      demand exceeding capacity.

PMID- 18334057
TI  - Uptake of 48-hour access appointments in genitourinary medicine.
AB  - Timely access to genitourinary (GU) medicine services is important in the control
      of sexually transmitted infections (STIs). A target has been set that by March
      2008, 100% of patients will be offered a GU medicine appointment within 48 hours.
      Strategic Health Authorities have also been asked to plan for 95% of patients to
      be seen within 48 hours. We sought to identify why patients decline appointments
      offered within 48 hours by collecting prospective data over three months.
      Additional data was collected over 18 working days to identify if alternative
      options would be acceptable to decliners. Overall, 1577 patients contacted the
      clinic, 1524 (96.6%) were offered a 48-hours appointment, 1108 (72.7%) accepted
      it, 416 (27.3%) declined it and 66.3% citing work commitments as the reason. In
      118 patients, who declined the appointment offered; 43.2% indicated no
      alternative option was acceptable, 23.7% chose a Saturday appointment, which in
      78.6% would have exceeded 48 hours. Hence, 73 (61.9%) patients would not have
      accepted an appointment within 48 hours. The balance of public health control,
      mixed service provision and informed patient choice is discussed.

PMID- 18334058
TI  - Hepatitis B testing and vaccination in patients recently diagnosed with HIV
      infection.
AB  - The British HIV Association currently recommends vaccination against hepatitis B
      virus (HBV) for all susceptible HIV-infected individuals, therefore a
      retrospective analysis was performed on case notes from all patients diagnosed
      with HIV infection in our department for a one-year period from 1st August 2005;
      in each case HBV serological testing and vaccination status were recorded. Fifty
      one patients were diagnosed with HIV infection during the study period, however,
      serological testing for HBV infection had been undertaken in only 76% of
      susceptible patients by 12 months following their HIV diagnosis. At the time of
      analysis only 31% of patients were adequately vaccinated against HBV, with
      recorded HBV surface antibody titres of >100 IU/L. HBV remains a considerable
      cause of morbidity and mortality in HIV-infected individuals and this study
      suggests that prevention or detection of HBV infection requires increased
      vigilance on the part of physicians managing HIV-positive patients.

PMID- 18334059
TI  - Sexual risk behaviour and HAART: a comparative study of HIV-infected persons on
      HAART and on preventive therapy in Kenya.
AB  - Unprotected sex (UPS) among persons receiving highly active antiretroviral
      therapy (HAART) remains a concern because of the risk of HIV-transmission. A
      cross-sectional study comparing the sexual risk behaviour of 179 people living
      with HIV/AIDS (PLHA) receiving HAART with that of 143 PLHA receiving preventive
      therapy (PT) with cotrimoxazole/isoniazid was conducted in Mombasa, Kenya. Forty
      five percent of all participants were sexually active in the last six months.
      Participants receiving PT were more likely to report > or =2 partners (13% vs.1%;
      P = 0.006). Participants receiving PT reported more UPS with regular partners
      (odds ratio [OR]: 3.9; 95% confidence interval [CI]: 1.8-8.4) and also more
      sexually transmitted infections (STI) symptoms (OR: 1.7; 95% CI: 1.0-2.8; P =
      0.059). More than 40% of all participants did not know the HIV-status of regular
      partners. Therefore, HAART was not associated with increased sexual risk
      behaviours though considerable risk of HIV-transmission remains. HIV-care
      services need to emphasize partner testing and consistent condom use with all
      partners.

PMID- 18334060
TI  - Slips, breaks and 'falls': condom errors and problems reported by men attending
      an STD clinic.
AB  - The objective was to comprehensively assess the prevalence of condom-use errors
      and problems among male clients attending a public sexually transmitted disease
      (STD) clinic. Men (n = 278) attending an STD clinic completed an anonymous
      questionnaire. Seven errors and six problems were assessed. Summative scores were
      tested for associations with three key variables. Of 834 condom-protected events:
      19% were associated with 'fit and feel' problems, 15% involved breakage, 14%
      involved lost erection, 9% were associated with lost erection while applying
      condoms, 8% involved slippage during withdrawal and 7% involved slippage during
      sex. A mean of 6.4 errors/problems were observed. None of these summative
      variables (total errors, total problems or total of errors and problems) were
      significantly associated with age, minority status or whether men indicated they
      had ever been taught how to use condoms. Multiple types of condom-use errors and
      problems may be highly prevalent among high-risk men attending public STD
      clinics.

PMID- 18334061
TI  - Psychosocial determinants of HIV-related quality of life among HIV-positive
      military in Nigeria.
AB  - There is a paucity of research regarding the role played by psychosocial and HIV
      related factors on quality of life (QoL) among military in developing countries.
      On presentation to a military hospital-based HIV clinic, 125 air-force personnel,
      56 seropositive (none of whom had AIDS) and 69 seronegative were interviewed. At
      the interview, participants were assessed using the Medical Outcome QoL and other
      psychosocial measures. The overall QoL was less among seropositive compared with
      seronegative air-force personnel. Seropositive personnel also reported a greater
      number of negative life events and trauma symptoms (post-traumatic stress
      disorder, PTSD). Seronegative military personnel reported more sexual risk
      behaviours compared with seropositive personnel. Multivariate analysis showed
      that trauma symptoms (PTSD) were a significant contributor to QoL and explained
      of the variance in physical, mental, role and social functioning among HIV
      infected air-force personnel. Other variables that predicted QoL, but to a lesser
      extent, included age, number of negative life events and increased
      symptomatology. These findings highlight the importance of evaluation of QoL in
      HIV-infected military personnel.

PMID- 18334062
TI  - HIV infection and the pancreas: risk factors and potential management guidelines.
AB  - One thousand and eighty-one evaluable HIV-infected patients were assessed for
      pancreatic abnormalities in a prospective case-control study including the whole
      follow-up period of each patient (minimum 12 months). The 435 patients (40.2%),
      who experienced at least one episode of confirmed pancreatic laboratory
      abnormality had a longer duration of seropositivity, exposure to protease
      inhibitors, a more frequent immunodeficiency, AIDS, chronic liver and/or biliary
      disease and hypertriglyceridaemia, while no relation was found with
      antiretroviral administration, and the duration of type of nucleoside analogues,
      when compared with the 646 controls. High and prolonged laboratory alterations
      eventually associated with signs of organ involvement occurred in 166 cases
      (38.2%), and were related to the administration of didanosine, stavudine,
      lamivudine, pentamidine, cotrimoxazole or antitubercular/antimycobacterial
      therapy, cytotoxic chemotherapy, illicit substance or alcohol abuse,
      opportunistic infections, chronic liver and/or biliary disease, a protease
      inhibitor-based highly active antiretroviral therapy (HAART) and
      hypertriglyceridaemia (usually associated with HAART administration). No
      difference was noticed between the 46 patients with clinical and/or imaging
      evidence of pancreatic involvement and the 120 asymptomatic subjects. Although
      recurrences of enzyme alterations involved 69.6% of patients, only in 30.1% of
      cases did a change of the underlying antiretroviral or antimicrobial therapy
      become necessary. An acute, uncomplicated pancreatitis occurred in nine of the 46
      symptomatic subjects (19.6%). A two to four week gabexate and/or octreotide
      administration (performed in 79 cases of 166, 47.6%), achieved a significant
      laboratory, clinical and imaging cure or improvement in 82.3% of cases, with a
      better success rate of combined (gabexate mesilate plus octreotide) vs. single
      (gabexate mesilate or ocreotide) therapy. Reduced disease recurrences and a
      better tolerability of antiretroviral regimens, were also noticed.

PMID- 18334063
TI  - Human papillomavirus type-distribution in the cervix of Chinese women: a meta
      analysis.
AB  - The aim of the study was to determine human papillomavirus (HPV) type
      distribution in the cervix of Chinese women, and to estimate the potential future
      impact of HPV prophylactic vaccines for cervical cancer prevention in China. A
      total of 32 studies using polymerase chain reaction for HPV detection were
      included in the meta-analysis, including 2844 invasive cervical cancer (ICC), 820
      high-grade squamous intraepithelial lesions (HSIL), 432 low-grade squamous
      intraepithelial lesions (LSIL) and 2902 women with normal cytology/histology. The
      overall and type-specific HPV prevalence of 18 HPV types (HPV 6, 16, 18, 31, 33,
      35, 39, 45, 51, 52, 56, 58, 59, 66, 68, 70, 73 and 82 of different cervical
      stages) were estimated. Overall HPV prevalence was 83.7%, 66.2%, 61.3% and 11.2%
      in ICC, HSIL, LSIL and normal, respectively. HPV 16 was the predominant type in
      all cervical stages. Estimated HPV 16/18 positive fractions in ICC, HSIL, LSIL
      and normal were 69.7%, 45.5%, 32.23% and 4.6%, respectively. HPV-16/18 vaccine
      has the 69.7% potential prevention in ICC. HPV 58 and 52 were the priority HPV
      types in Chinese women.

PMID- 18334064
TI  - Syndromic approach to sexually transmitted infections in Tunisian women:
      bacteriological validation.
AB  - The World Health Organization emphasizes an integrated primary care approach
      using syndromic management of sexually transmitted infections. The objective of
      our study was to evaluate the quality of care of the syndromic management of
      sexually transmitted disease in women in Rabta hospital in Tunisia. Algorithms
      have been developed for: cervicitis due to Neisseria gonorrhoeae or Chlamydia
      (algorithm 3a), vaginitis due to Trichomonas vaginalis or Chlamydia trachomatis
      (algorithm 3b) and vaginitis due to Candida (algorithm 3c). A total of 116 women
      were enrolled in the study during February 2003 to April 2004. The prevalence of
      each bacterium was Chlamydia (10%), N. gonorrhoeae (1%), Treponema pallidum (1%),
      T. vaginalis (5%) and Candida (21%). Algorithm '3a' had a sensitivity of 45%, a
      specificity of 42% and positive predictive value (PPV) of 11.9%. Algorithm '3b'
      had a sensitivity of 35.7%, a specificity of 68.9% and PPV of 20.8%. Algorithm
      '3c' had a sensitivity of 12%, a specificity of 88% and PPV of 33.3%. To improve
      the sensitivity of the syndromic approach, we suggest improving the quality of
      history taking.

PMID- 18334065
TI  - Adolescents' reasons for using a microbicide-like product over time.
AB  - This study examined the reasons that adolescent girls used a product over time.
      Adolescent girls (n = 208; 14-21 years) participated in a six-month study in
      which they completed three face-to-face interviews and 24-weekly phone call
      interviews. Participants were given microbicide-like products (vaginal
      lubricants) and encouraged to use them with condoms when they had intercourse.
      Most of the reasons for use were endorsed by most of the adolescent girls, at
      some time during the study. Over time, the adolescents were significantly more
      likely to report the following reasons for use: did not think the product would
      leak out (z = 2.49; P < 0.01), the product felt comfortable (z = 2.41; P < 0.02)
      and the product was not messy to use (z = 3.11; P < 0.01). Although it appears
      that adolescents are interested in microbicides, they may worry about certain
      characteristics of the product. It will be important to develop anticipatory
      guidance that focuses on the experience of using the product, making sure
      adolescent girls continue to use over time.

PMID- 18334066
TI  - A retrospective clinical study of the treatment of high-grade anal dysplasia by
      infrared coagulation in a population of HIV-positive men who have sex with men.
AB  - HIV-positive men who have sex with men (MSM) are at high risk of developing human
      papillomavirus-associated anal squamous cell cancer. Similar to the management of
      cervical dysplasia, clinicians are treating high-grade anal dysplasia to prevent
      progression to cancer. Initial treatments such as cold scalpel excision and
      electrofulguration have shown limited efficacy in a HIV-positive population.
      Infrared coagulation (IRC) is an outpatient treatment for high-grade anal
      dysplasia. This retrospective clinical study reports on 68 HIV-positive MSM with
      78 biopsy proven high-grade anal lesions. Each lesion was treated with the IRC
      with re-biopsy of the treatment site a mean of 140 days later. Of the 74
      evaluable lesions; 39 had anal intraepithelial neoplasia (AIN) 1, 20 had AIN 2,
      seven had AIN 3, and eight had normal epithelium. The IRC showed 64% efficacy per
      treated lesion and shows promise as a treatment modality for high-grade anal
      dysplasia in this population.

PMID- 18334067
TI  - An audit of the interval to treatment of anogenital Chlamydia trachomatis at
      Scottish genitourinary medicine clinics.
AB  - Timely treatment of sexually transmitted infections can reduce complications and
      prevent onward transmission. Several audit standards exist in this area. We
      audited the timeliness of treatment of 538 episodes of chlamydia at 12 Scottish
      genitourinary medicine clinics against a national standard and against a local
      best practice target. Three clinics treated 95% of patients within two weeks and
      10 clinics treated 95% of patients within four weeks. All clinics treated 60% of
      patients within four weeks. Overall, all clinics performed well against published
      standards, but less well against the best practice target.

PMID- 18334068
TI  - A retrospective audit of the management and complications of pelvic inflammatory
      disease.
AB  - Our objective was to examine the management of pelvic inflammatory disease (PID)
      in Southend Hospital against the British Association for Sexual Health and HIV
      guidelines. In addition, we reviewed the Genito-Urinary (GU) Medicine and
      Gynaecology notes for patients who failed treatment for PID in GU medicine. This
      was to reveal their complications and subsequent management. Thirty of 249
      patients diagnosed with PID failed treatment. Chlamydia was found in 30% of these
      patients, gonorrhoea in 10%, with the rest being categorized into presumed
      anaerobic/other aetiology. Appropriate antibiotic regimens were used in 96.6% of
      patients and the 66.7% of contacts who were traced and treated. Eighteen of the
      30 patients had a laparoscopy. Findings were: confirmed PID in 5.6%;
      endometriosis in 27.8%, adhesions with no evidence of PID in 27.8%; and 38% had
      no abnormalities found. Laparoscopy has an important role in excluding other
      pathology in patients who have failed to respond to appropriate conservative
      management.

PMID- 18334069
TI  - Self-reported reasons among HIV-infected patients for missing clinic
      appointments.
AB  - Although adherence to clinic visits is important for successful clinical outcome
      in HIV treatment, little is known about the reasons patients with HIV miss
      appointments. We prospectively monitored the self-reported reasons for missed
      clinic appointments among HIV patients at a university hospital in South Korea
      from June through December 2006. Of the 1562 scheduled clinic visits, 131 (8%) of
      appointments were missed. Work schedule, forgetfulness and lack of motivation
      were the primary reasons given for missed appointments. Considering these factors
      when scheduling appointments may improve adherence to clinic attendance among HIV
      infected patients.

PMID- 18334070
TI  - An audit of completeness of HIV clinical histories: before and after introduction
      of an HIV proforma.
AB  - The completeness of a 'first consultation' human immunodeficiency virus (HIV)
      clinical history before and after the introduction of an HIV proforma was audited
      by a retrospective case notes review. Twenty key variables considered essential
      to every history were assessed. There was a significant improvement in the
      documentation of 14 of the 18 items for men and 14 of the 20 items for women post
      proforma with no deterioration in documentation of any of the variables. Our
      study supports the introduction of a structured 'first consultation' notes
      proforma for use during consultations with both newly diagnosed HIV-positive
      patients and those transferring their care from other centres.

PMID- 18334071
TI  - Transmission of Chlamydia and genital warts during sleepwalking.
AB  - A boy aged 15 years infected a girl of 13 years with Chlamydia and genital warts.
      The boy has been engaged in sexual activities for the last four years. There was
      no dispute that the boy had had sex with the girl. He was prosecuted but
      acquitted by the Court on the ground of 'defence of sleepwalking'. This is the
      first case where sexually transmitted infections like Chlamydia and genital warts
      have been transmitted sexually through sleepwalking. This case also raises the
      issues of underage sex and issues of confidentiality.

PMID- 18334072
TI  - Transmission of HIV-1 infection due to a fist fight.
AB  - We report a case of HIV-1 infection transmission caused by a fist fight between
      brothers. A 30-year-old Caucasian UK resident man developed 'flu-like illness
      with symptoms of lethargy and weakness. Persistent lymphadenopathy six months
      later lead to HIV antibody testing, which was positive. Of note, his 37-year-old
      brother, who was HIV antibody-positive since August 2000, was taking HAART
      (combivir and nevaripine) with CD4 350 x 106/L (16%) with viral load 4800
      copies/mL (log 2.58). A bloody fight had occurred between them four weeks prior
      to onset of symptoms. Phylogenetic analysis was undertaken. Analysis of the pol
      gene region indicated that samples from both brothers belonged to the subtype C
      clade of HIV-1, and that the sequences were closely related to one another.
      Exposure risk data are extremely useful in helping counsel patients prior to HIV
      testing but, as this case illustrates, does not cover all situations.

PMID- 18334073
TI  - Malignant melanoma masquerading as Kaposi's sarcoma.
AB  - A homosexual HIV-negative man was referred to the genitourinary medicine
      department with a histological diagnosis of Kaposi's sarcoma. Repeat biopsy
      confirmed that this was in fact malignant melanoma.

PMID- 18334074
TI  - Immune reconstitution syndrome associated with leprosy: two cases.
AB  - Few cases of leprosy as immune reconstitution syndrome have been reported in
      patients with HIV/AIDS. Two cases of leprosy as immune reconstitution syndrome in
      AIDS persons are described, and clinical features, diagnostic criteria and
      pathogenesis are discussed.

PMID- 18334075
TI  - Vitamin D intoxication: a cause of hypocalcaemia and acute renal failure in a HIV
      patient.
AB  - Hypercalcaemia in patients with HIV infection is usually associated with specific
      conditions such as lymphoma and granulomatous diseases. We described a case of
      severe hypercalcaemia consequent to vitamin D intoxication and secondary renal
      failure in a HIV patient under tenofovir using. Serum creatinine and calcium
      returned to near normal levels after vitamin D discontinuation, saline and
      furosemide administration. Some aspects of the drug-induced nephropathy are
      discussed.

PMID- 18334076
TI  - Lymphogranuloma venereum in the UK in 2003.
AB  - Lymphogranuloma venereum in the United Kingdom was detected in 2004, following
      the introduction of enhanced surveillance. This report describes a previously
      undiagnosed case, detected retrospectively in a sample obtained in 2003 from a
      male patient with high-risk behaviour, indicating that this previously rare
      disease in Europe, was present in the UK in 2003.

PMID- 18334077
TI  - Successful reversal of threatening carotid artery occlusion in HIV-associated non
      aneurysmal vasculitis.
AB  - We report a case of HIV-associated carotid vasculitis, causing cerebral
      infarction. Immediate corticosteroid treatment was followed by improvement, with
      radiological documentation of reversal of the vasculitic changes, preventing
      arterial occlusion. Vasculitis should be considered as a diagnosis in stroke in
      HIV and steroid treatment considered as a potentially life-saving intervention.

PMID- 18334078
TI  - Use of opt-out in a trial of chlamydia screening.

PMID- 18334079
TI  - Chaperones: getting the balance right.

PMID- 18334080
TI  - The changing face of sexually transmitted infections in pregnancy in Limerick,
      Ireland, over 18 years.

PMID- 18334081
TI  - Association between perioperative NSAID use and post-cardiothoracic surgery
      atrial fibrillation, blood transfusions, and cardiovascular outcomes: a nested
      cohort study from the AF Suppression Trials (AFIST) I, II and III.
AB  - BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use may reduce the
      incidence of post-cardiothoracic surgery (CTS) atrial fibrillation (AF). The
      cerebrovascular and cardiovascular safety of using NSAIDs for post-CTS AF has not
      been determined. OBJECTIVE: To evaluate whether NSAIDs could reduce the incidence
      of post-CTS atrial fibrillation without increasing patients' risk of stroke or
      myocardial infarction (MI). METHODS: Patients (n = 555) undergoing CTS from the
      Atrial Fibrillation Suppression Trials I, II and III were evaluated in this
      nested cohort study. Demographic, surgical and medication use characteristics
      were prospectively collected as part of the AFIST trials. Endpoints included post
      CTS atrial fibrillation, stroke, MI and the need for red blood cell transfusion.
      Multivariable logistic regression was used to control for potential confounders
      and calculate adjusted odds ratios with 95% confidence intervals. RESULTS: The
      population was 67.8 +/- 8.6 years old and 77.1% male with 127 (22.9%) patients
      receiving an NSAID postoperatively. Overall, 14.6% underwent valve surgery, 6.1%
      had prior AF, 12.6% had heart failure and 84.0% and 44.1% received postoperative
      beta-blockade and prophylactic amiodarone. NSAID use was associated with
      reductions in the adjusted odds of post-CTS atrial fibrillation (0.54 (0.32
      0.90)) and the need for RBC transfusions (0.63 (0.41-0.97)). No elevation in the
      odds of developing stroke (1.10 (0.21-5.66)) or MI (1.70 (0.40-7.10)) was
      observed. LIMITATIONS: Patients were not randomized to receive NSAIDs versus a
      control. We may not have had adequate power to evaluate stoke or MI in this
      analysis. CONCLUSIONS: NSAIDs decreased the odds of developing post-CTS atrial
      fibrillation, further supporting the hypothesis of inflammation as a trigger for
      post-CTS atrial fibrillation. The need for RBC transfusions was also reduced with
      NSAID use. We may have been underpowered to evaluate stroke or MI incidence, but
      the qualitative elevations in these variables suggest more safety data is needed
      before NSAIDs can be routinely recommended.

PMID- 18334082
TI  - In vitro disintegration and dissolution studies of once-weekly copies of
      alendronate sodium tablets (70 mg) and in vivo implications.
AB  - OBJECTIVE: The aim of this study was to evaluate the in vitro disintegration and
      dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada,
      Germany, the Netherlands, and the United Kingdom compared to the branded product
      (Fosamax). RESEARCH DESIGN AND METHODS: The disintegration and dissolution times
      were determined using the methods described in the United States Pharmacopeia 30
      (USP 30). The disintegration of four orally disintegrating tablets (non
      bisphosphonates) and branded film-coated risedronate sodium tablets were included
      for comparison. RESULTS: The mean disintegration times of the alendronic acid
      tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for
      Betapharm (Germany). The mean disintegration time of the branded product tablets
      ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets
      with very rapid disintegration times which are similar to those of orally
      disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with
      very rapid mean disintegration times are as follows: Pharmachemie (Netherlands),
      14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma
      (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s.
      Since there is no established disintegration time for alendronic acid tablets
      there can be no assurance that the copy tablets are equivalent to the branded
      product in terms of esophageal drug exposure. However, the in vitro
      disintegration times have not been correlated with in vivo disintegration and
      performance. The dissolution of all the bisphosphonate tablets was rapid with
      greater than 80% dissolved in 15 min and all products conformed to the USP 30
      specification. CONCLUSIONS: The dissolution of all alendronic acid tablets was
      rapid and complete and conformed to the established USP 30 specifications which
      should ensure adequate drug absorption from the copy products. However, copies of
      alendronic acid tablets are approved based on the results of single-dose
      bioavailability studies in healthy subjects and this is not adequate to establish
      similar disintegration characteristics.

PMID- 18334083
TI  - Construing stigmatized identities: a golden section study.
AB  - OBJECTIVES: In order to examine whether persons belonging to stigmatized groups
      are evaluated more negatively than others, this study employed the golden section
      hypothesis, which predicts that people organize their evaluations in a ratio of
      roughly 62% positive to 38% negative. METHOD: Surveys were administered to 154
      participants, with 143 surveys analysed. Participants rated nine different
      identities (business person, politician, lawyer, police officer, college
      professor, criminal, mental patient, homeless person, and self) along 12
      different bipolar dimensions (generous-stingy, pleasant-unpleasant, true-false,
      fair-unfair, active-passive, energetic-lethargic, sharp-dull, excitable-calm,
      strong-weak, bold-timid, hard-soft, and rugged-delicate). These dimensions had
      well-established positive and negative poles. RESULTS: Non-stigmatized identities
      were evaluated slightly more positively than the golden section hypothesis
      predicts, while stigmatized identities were rated in a 'reverse' golden section
      pattern. A criminal identity was rated more negatively than the golden section
      hypothesis predicts and the self more positively. Follow-up analyses suggested
      that the percentages of positive adjectives assigned to the self and non
      stigmatized others were consistent with a model that expands upon the golden
      section hypothesis. CONCLUSION: Stigmatized identities are rated using a reverse
      golden section ratio. This has implications for understanding how people construe
      stigmatized people. While the golden section hypothesis did not hold for non
      stigmatized identities, this may be because the data are better explained by a
      more refined model that is slightly different from the golden section.

PMID- 18334084
TI  - A rapid simple approach to screening pharmaceutical products using ultra
      performance LC coupled to time-of-flight mass spectrometry and pattern
      recognition.
AB  - The comparison of batches of pharmaceutical product or raw active pharmaceutical
      ingredients (API) for product release can be time consuming and tedious process.
      It often requires long analysis times and potentially several liquid
      chromatography-tandem mass spectrometry (LC-MS-MS) analytical runs to determine
      the identity of the impurities and their relationship to the active
      pharmaceutical ingredient. The combination of a high resolution (sub 2 microm
      porous particle) LC coupled to exact mass MS, principal components analysis (PCA)
      allowed for the rapid classification of batches of Simvastatin tablets according
      to their impurity profile. Evaluating the ultra-performance LC-MS exact mass data
      with PCA allowed for the impurities of Simvastatin to be easily detected and
      identified. This approach to impurity batch analysis should be applicable to many
      other forms of batch analysis, fermentation broths, food production, and API
      manufacturing.

PMID- 18334085
TI  - Pharmaceutical applications on columns packed with sub-2 microm particles.
AB  - During the last few years, there has been a great interest in the development of
      fast liquid chromatography. Among the reported approaches, the reduction of the
      particle size to attain sub-2microm diameter represents a good solution for
      achieving both increased separation power and faster analysis time. This paper
      demonstrates the chromatographic performance of such supports using plate-height
      curves and reveals the possibility for obtaining ultra-fast or highly efficient
      separations, according to the column geometry and system pressure limitations.
      The stability of these columns is initially evaluated using a system suitability
      experiment. The chromatographic performance remains stable in terms of retention,
      efficiency, and pressure for more than 1700 injections with pressure conditions
      ranging from 200 to 800 bar. Several fast and ultra-fast pharmaceutical
      applications are reported. In isocratic mode, a 5- to 10-fold reduction in
      analysis time is obtained with limited influence on efficiency and resolution.
      The run time is further reduced by 30-fold with the shorter available columns
      (i.e., 30 mm length). In gradient mode, the separation of a complex mixture
      containing an active pharmaceutical compound and related impurities is
      significantly improved with column length equal to 100 mm, to increase peak
      capacity and resolution.

PMID- 18334086
TI  - Evaluation of BEH C18, BEH HILIC, and HSS T3 (C18) column chemistries for the
      UPLC-MS-MS analysis of glutathione, glutathione disulfide, and ophthalmic acid in
      mouse liver and human plasma.
AB  - Glutathione (GSH), glutathione disulfide (GSSG), and ophthalmic acid (OA) are
      important biological oxidative stress biomarkers to be monitored in pathological
      and toxicological studies. With the advent of liquid chromatography tandem mass
      spectrometry (LC-MS-MS) technology, sensitive and selective analysis of these
      biomarkers in biological samples is now being performed routinely. Due to the
      hydrophilic and polar natures of GSH and its endogenous derivatives, achieving
      good retention, resolution, and peak shape is often a chromatographic challenge.
      In this study, three ultra-performance (UP) LC column chemistries (namely, BEH
      C18, BEH HILIC, and HSS T3 [C18]) are evaluated for the UPLC-MS-MS analysis of
      GSH, GSSG, and OA extracted from mouse liver and human plasma samples. The
      chromatographic parameters evaluated are retentivity, tailing factor, MS
      sensitivity, and resolution of the three analytes. Based on the optimized method
      for each column chemistry, our results indicate that the HSS T3 (C18) column
      chemistry affords the best retention and separation of these analytes when
      operated under the ultra high-pressure chromatographic conditions.

PMID- 18334087
TI  - Urinary excretion study of coenzyme Q10 in rats by ultra-performance liquid
      chromatography-mass spectrometry.
AB  - A method based on ultra-performance liquid chromatography mass spectrometry (UPLC
      MS) applying atmospheric pressure chemical ionization in the positive ion mode is
      developed for the determination of coenzyme Q10 (CoQ10) in rat urine. The assay
      involves the extraction of crude urine, fast liquid chromatography on a Waters
      Acquity UPLC BEH C18 column (1.7 microm, 1.0 x 50 mm), and selected ion
      monitoring detection using mass transition. The calibration range is found to be
      0.05-25 microg/mL, with the lower limit of quantitation of 0.05 microg/mL. Intra-
      and inter-day precision (relative standard deviation) for CoQ10 in rat urine
      range from 0.7% to 15%, and accuracy expressed in recovery rates in urine is
      between 83% and 118%. The recovery of this method is found to be between 80% and
      95% at three concentrations. The total cumulative recovery of CoQ10 is 1.16 +/-
      1.05% (percentage of dose intake, n = 4) from rat urine collected over 30 h after
      oral administration of the drug. The UPLC-MS method described allows the quick
      determination of CoQ10 in rat urine with good precision and accuracy. It is
      suitable for further excretion studies of CoQ10 in animals.

PMID- 18334088
TI  - Determination of Paclitaxel in Human Plasma by UPLC-MS-MS.
AB  - A sensitive and specific ultra-performance liquid chromatography-tandam mass
      spectrometry method for the quantitation of paclitaxel is established. A 200
      microL human plasma sample is spiked with 13C6-labeled paclitaxel as an internal
      standard and extracted with 1.3 mL of tert-butyl methyl ether. The
      chromatographic separation is achieved within 2 min on a C18 column with methanol
      0.1% aqueous formic acid (75:25, v/v) as a mobile phase at a flow rate of 0.4
      mL/min. Multiple reaction monitoring mass transitions of m/z 876.2 to 307.9 and
      882.2 to 313.9 are measured for paclitaxel and the internal standard,
      respectively. For paclitaxel at the concentrations of 1.021, 5.105, and 10.21
      microg/mL in human plasma, the extraction recoveries are 105.87%, 103.91%, and
      100.39%, respectively. The linear quantitation range of the method is 0.1021
      20.42 microg/mL in human plasma with a correlation coefficient greater than
      0.999. The intra- and inter-day accuracy for paclitaxel at 1.021, 5.105, and
      10.21 microg/mL levels in human plasma fell in the ranges of 95.01-99.23% and
      95.29-101.28%, and the intra- and inter-day precision were in the ranges of 6.37
      10.88% and 7.21-9.05%, respectively. This method is successfully applied to the
      determination of the half-life of paclitaxel in human plasma.

PMID- 18334090
TI  - Determination methods for biologically active compounds by ultra-performance
      liquid chromatography coupled with mass spectrometry: application to the analyses
      of pharmaceuticals, foods, plants, environments, metabonomics, and metabolomics.
AB  - This review summarizes the determination methods for biologically active
      compounds, such as pharmaceuticals, agrochemicals, and biogenic amines, by ultra
      performance liquid chromatography coupled with mass spectrometry. The typical
      applications using the method are also described in this study, together with the
      characteristics of the methods.

PMID- 18334089
TI  - Simultaneous determination of four water-soluble vitamins in fortified infant
      foods by ultra-performance liquid chromatography coupled with triple quadrupole
      mass spectrometry.
AB  - A novel ultra-performance liquid chromatography electrospray ionization tandem
      triple quadrupole mass spectrometry method for the simultaneous determination of
      four water-soluble vitamins, including vitamin B5 (VB5), vitamin B8 (VB8),
      vitamin B9 (VB9), and vitamin B12 (VB12) in fortified infant foods is developed
      and validated. A reverse phase UPLC separation system consisting of a Waters
      ACQUITY UPLC BEH C-18 column (2.1 mm x 100 mm i.d., 1.7 microm) and a binary
      gradient acetonitrile-water mobile phase is applied for the separation of the
      four water-soluble vitamins. Formic acid is spiked into the mobile phase to
      enhance the ionization efficiency. Tandem MS-MS analysis is performed in multi
      reaction monitoring mode (MRM). Product-ion traces at m/z 220.1 --> 89.9 for VB5,
      245.1 --> 227.1 for VB8, 442.3 --> 295.2 for VB9, and 678.9 --> 147.0 for VB12
      are used for quantitation of the corresponding vitamins, and traces at m/z 455.5 
      -> 308.0 are used for methotrexate (internal standard). Limits of quantitation
      (LOQs) are 0.016, 0.090, 0.020, and 0.019 microg/L for VB5, VB8, VB9, and VB12,
      respectively. Intra- and inter-day precisions for the determination of the four
      vitamins are better than 6.84% and 12.26% in relative standard deviations, and
      recoveries for the four vitamins are in the range of 86.0~101.5%. The developed
      approach is applied for the determination of the trace amounts of the vitamins in
      fortified milk powers and fortified rice powers.

PMID- 18334091
TI  - Ultrahigh-pressure liquid chromatography: fundamental aspects of compression and
      decompression heating.
AB  - Ultrahigh-pressure liquid chromatography is an emerging technique for carrying
      out rapid and highly efficient separations. Unfortunately, one of the simplifying
      assumptions made in conventional high-performance liquid chromatography,
      incompressibility of the mobile phase, is not valid when higher and higher
      pressures are used. Rather, both compression and decompression of the eluent must
      be considered in terms of both heating and changes in the solvent's structure.
      The first of these problems, eluent heating during the compression and
      decompression cycles, which occurs in the pump and column, respectively, are
      considered in terms of a combined first principle-empirical approach that is
      solved (i.e., an analytic solution obtained from the resulting integral equation)
      using 0.01 Bar pressure steps. The approach is used to estimate compression and
      decompression heating for methanol and water.

PMID- 18334092
TI  - Characteristics of superficially-porous silica particles for fast HPLC: some
      performance comparisons with sub-2-microm particles.
AB  - Columns of 2.7-microm fused-core (superficially porous) Type B silica particles
      allow very fast separations of small molecules at pressures available in most
      high-performance liquid chromatography instruments. These highly-purified
      particles with 1.7-microm solid silica cores and 0.5-microm-thick shells of 9 nm
      pores exhibit efficiencies that rival those of totally porous sub-2-microm
      particles but at one-half to one-third of the column back pressure. This
      presentation describes other operating features of fused-core particle columns,
      including sample loading characteristics and packed bed stability. The superior
      mass transfer (kinetic) properties of the fused-core particles result in much
      improved separation efficiency at higher mobile phase velocities, especially for
      > 600 molecular weight solutes.

PMID- 18334093
TI  - Options for rapid analysis of peptides and proteins, using wide-pore,
      superficially porous, high-performance liquid chromatography particles with
      unique bonded-phase ligands.
AB  - The large size and complexity of many proteins constrains the reversed-phase high
      performance liquid chromatography packings that are useful for their separation.
      Wide-pore, superficially porous, silica-based packings with solid 4.5-microm
      cores and a 0.25-microm porous outer layer (Poroshell) demonstrate a variety of
      characteristics that are beneficial for the separation of proteins. A shorter
      diffusion distance allows separations of large molecules at high linear
      velocities. This benefit over totally porous particles is clearly shown using
      separations of a peptide-protein standard. The structure and reduced surface area
      (4.5 m2/g) of these superficially porous particles simplifies interactions with
      its surface, resulting in improved peak shapes and resolution. Specialized
      bonding chemistries for low- and high-pH operation may be used to change band
      spacing and achieve atypical separations. These rapid analysis options are
      demonstrated using protein standards and very high molecular weight glycosylated
      proteins including intact monoclonal antibodies, IgM, alpha2-macroglobulin, and
      glycophorin. In liquid chromatography-mass spectrometry analysis of a myoglobin
      peptide digest, bidentate-C18-bonded superficially porous packings achieve
      complete runs in 4 min and demonstrate an elution pattern that is unique from
      that of material bonded with sterically protected C18 ligands.

PMID- 18334094
TI  - Monitoring stereoselective degradation of metolachlor in a constructed wetland:
      use of statistically valid enantiomeric and diastereomeric fractions as opposed
      to ratios.
AB  - Environmentally contaminated aqueous samples are examined for evidence of
      stereoselective degradation of metolachlor. The unique chemical structure of
      metolachlor, a chloroacetamide herbicide, consists of four stereoisomers due to
      axial and/or C-chirality. The degradation of metolachlor is monitored over time
      in agricultural runoff water that is applied to a subsurface flow constructed
      wetland. Metolachlor stereoisomers are isolated from aqueous samples by achiral
      reversed-phase solid-phase extraction and analyzed by normal-phase high
      performance liquid chromatography using a chiral stationary phase. The analyses
      of 64 post-application samples, collected over a period of four weeks, are
      reported. The samples are filtered (0.45 microm) prior to analysis and thereby
      represent metolachlor in solution and/or associated with dissolved organic
      carbon. Sixteen samples demonstrate total racemic metolachlor concentrations
      greater than 10 ppb. Of these 16 samples, one sample is determined statistically
      to demonstrate enantioselective degradation. Significant contributions made by
      this study include the evaluation of stereoselectivity based on mathematically
      derived fractions, rather than ratios, and statistical evaluation of precision
      establishing the variability resulting from chromatographic processes versus
      metabolic processes. The research demonstrates that distribution of metolachlor
      between the solid phase composed of chemical and/or biological particulates and
      the aqueous phase is not primarily stereoselective, and that stereoselectively
      enriched metolachlor does not dominate in the aqueous phase.

PMID- 18334095
TI  - On-line microdialysis coupled to analytical systems.
AB  - In vivo sampling of interstitial fluid using microdialysis (MD) fibers has become
      a standard and accepted procedure. The resulting small volume samples, often with
      low concentrations of the analyte of interest, present a particular challenge to
      analytical methods. Rapid developments of analytical techniques with high
      sensitivity accelerate their combination with MD. On-line MD-based analytical
      systems are receiving increasing attention because they can provide near real
      time data prior to the off-line system. The purpose of this review is to provide
      information for on-line MD-analytical systems. Special emphasis has been given to
      the main progression on methodologies of each method during recent years. The
      advantages, limitations, and adaptivity are also discussed. These methods include
      on-line MD-liquid chromatography, on-line MD-capillary electrophoresis, on-line
      MD-mass spectrometry, and on-line MD-biosensor.

PMID- 18334096
TI  - Optimization of an LC-MS method for the determination of artesunate and
      dihydroartemisinin plasma levels using liquid-liquid extraction.
AB  - Artesunate is a derivate of artemisinin, an antimalarial drug used for the
      treatment of malaria caused by Plasmodium falciparum and related parasites.
      Artesunate is hydrolyzed rapidly to dihydroartemisinin in vivo. It has been found
      that artemisinin and its derivatives may have neurotoxic effects. A method was
      developed to analyze human plasma samples for the contents of artesunate and
      dihydroartemisinin. The plasma samples are extracted with ethyl acetate,
      concentrated, and redissolved in water/acetonitrile. Analyses was performed with
      liquid chromatography-mass spectrometry using a binary gradient program with
      aquaeous formic acid and acetonitrile formic acid on a XTerra MS C18-column. The
      mass spectrometer was operated in the positive atmospheric pressure chemical
      ionization mode with single ion recording. The lower limits of detection were 10
      and 25 ng/mL plasma for DHA and artesunate, respectively. The method was
      validated according to the guidelines for validation of bioanalytical methods.

PMID- 18334098
TI  - Quantitation of seven low-dosage antipsychotic drugs in human postmortem blood
      using LC-MS-MS.
AB  - In forensic toxicology, antipsychotic drugs are of considerable interest because
      of their abuse potential and their involvement in intoxications and suicides. In
      recent years, several new drugs dosed at low levels have entered the market and
      have put further demands on assays used. The aim of this work was to develop a
      validated liquid chromatography-tandem mass spectrometry assay for the
      quantitation of the low-dosage antipsychotic drugs buspirone, fluphenazine,
      flupenthixol, perphenazine, risperidone, ziprasidone, and zuclopenthixol in human
      postmortem blood. After liquid-liquid extraction using methyl t-butyl ether,
      compounds were separated on a Zorbax SB-CN column. Calibration curves were linear
      in the range 0.8-100 microg/L (r > 0.998) for all drugs. Both within- and between
      day coefficients of variation were lower than 25% for all drugs at the LOQ, and
      extraction recoveries ranged between 58 and 112%. The possible presence of matrix
      effects was closely investigated. Fifty-four authentic samples were analyzed
      within the routine postmortem investigation, which resulted in the diagnosis of
      three fatal intoxications. Even though only a few intoxications were identified,
      the assay may present valuable information on suicidal deaths in psychotic
      patients where a true negative result implies noncompliance and a higher
      susceptibility for suicide. Without a sensitive enough method, this conclusion
      cannot be drawn. Therefore, we believe that antipsychotic drugs must be measured
      not only in toxic concentrations but also in therapeutic levels in postmortem
      cases.

PMID- 18334097
TI  - Accumulation, fractionation, and analysis of platinum in toxicologically affected
      tissues after cisplatin, oxaliplatin, and carboplatin administration.
AB  - Antitumoral Pt-containing drugs present side effects like nephrotoxicity and
      ototoxicity. Several systematic experiments have been carried out with Wistar
      rats treated with cisplatin, carboplatin, and oxaliplatin to study Pt-drugs
      accumulation and elimination, and Pt-biomolecule distribution in the cells and
      cytosols of ear, kidney, and liver. Inductively coupled plasma-mass spectrometry
      (ICP-MS) analysis shows a cisplatin accumulation capability between oxaliplatin
      (the highest) and carboplatin (the lowest). The maximum concentration of Pt in
      all the organs studied was achieved around the first week after cisplatin
      treatment. During the first 30 days, the elimination was very fast, decreasing in
      the subsequent 60 days in all the organs. Analysis of cytosols by liquid
      chromatography (LC)-ICP-MS showed an analogous behavior. In most samples, the
      distribution of the three drugs in the cellular and cytosolic fractions was
      similar for all the tissues. For kidney and ear, approximately 60% and 30%,
      respectively, of the metal accumulated was present in the cytosol, the cytosolic
      fractions smaller than 50 KDa being especially important. Cisplatin-biomolecule
      interaction strength under denaturing conditions was evaluated by LC-ICP-MS and
      showed a quite strong bond.

PMID- 18334099
TI  - Ethanol contamination leads to Fatty acid ethyl esters in hair samples.
AB  - The diagnosis of alcoholism is a topical subject of discussion; in fact, many
      studies have been published on the determination of biochemical markers useful to
      this target. Fatty acid ethyl esters (FAEE) are minor metabolites of ethanol, and
      their usefulness has been demonstrated by their detection in hair using a
      headspace solid-phase microextraction-gas chromatographic-mass spectrometric
      technique. Environmental contamination in the analysis of drugs of abuse is a
      well-known focus of discussion between scientists. In the same way, interference
      from the surroundings could be hypothesized in FAEE detection. To assess the
      influence of ethanol contamination, an in vitro experiment was performed, leaving
      hair in an atmosphere saturated with ethanol vapors for 15 days. The spontaneous
      production of FAEE was demonstrated by analyzing hair day by day. In fact, we
      observed a constant increase of ethyl myristate, palmitate, and stearate that
      reached very high concentrations at the end of the investigation. Although the
      experiment was managed in a stressed way and could not represent real life, its
      purpose was to focus the attention of researchers on the problem of hair
      contamination that can occur, for example, with ethanol-containing cosmetics.
      Therefore, care in interpretation must be taken into account, especially with
      such a volatile molecule.

PMID- 18334100
TI  - Cannabinoid concentrations in spot serum samples 24-48 hours after
      discontinuation of cannabis smoking.
AB  - A blood concentration of tetrahydrocannabinol (THC) in the low nanograms-per
      milliliter range is often claimed to result from drug use more than 24-48 h
      previously. The present investigation determined concentrations of cannabinoids
      in blood collected at least 24 h from smoking in an in-patient setting. During
      sampling, distinctive effects due to drug use could not be observed. The randomly
      collected samples from heavy (n = 16, > 1 joint/day), moderate (n = 15, < or = 1
      joint/day), and light (n = 6, < 1 joint/week) users of cannabis were analyzed for
      THC, 11-hydroxy-THC (OH-THC), and free 11-nor-9-carboxy-THC (THCCOOH) by gas
      chromatography-mass spectrometry as well as for glucuronidated THCCOOH by liquid
      chromatography-tandem mass spectrometry. THC was detectable in 9, 6, and 1
      samples from heavy, moderate, and light users, respectively. Although cannabinoid
      concentrations were overlapping between groups, there was a trend towards higher
      concentrations of both conjugated and free THCCOOH in regular users compared to
      occasional users. The present findings appear to indicate that low levels of THC,
      or of THC along with OH-THC, may not unequivocally prove a very recent use of
      cannabis.

PMID- 18334101
TI  - A comparison of methadone, oxycodone, and hydrocodone related deaths in Northeast
      Ohio.
AB  - Increases in methadone and oxycodone related deaths have been recently documented
      in the United States. In response to these reports, the authors investigated
      cases over a six-year period in which postmortem toxicological analyses revealed
      the presence of methadone, hydrocodone, and oxycodone. The study was designed to
      determine whether regional methadone-associated mortality in Cuyahoga County
      reflected national trends and more specifically, to distinguish methadone
      mortality from other commonly used opioid analgesics. All records of decedents
      that were found to be positive for methadone, hydrocodone, and/or oxycodone in
      1998-2003 were reviewed. The cause and manner of death and demographic
      information was compiled. The cases were divided into lethal intoxications and
      cases where a positive result was determined to be an incidental finding. Lethal
      intoxications as a result of only methadone, hydrocodone, or oxycodone were
      separated from polydrug intoxications. Thoroughout the study, an increase was
      observed in the number of positive cases. In contrast to recent national data,
      although the number of methadone-positive cases increased from 4 in 1998 to 18 in
      2003, this did not result in an increase in methadone overdoses [1 death in 1998
      (25%) to 4 deaths in 2003 (22%)]. Although the pharmacokinetic profiles differ,
      methadone, hydrocodone, and oxycodone lethal intoxications equally comprised 28
      29% of cases in which these drugs were detected. There was an overlap in the
      range of blood concentrations observed for the drug-related death groups and the
      incidental finding groups. However, mean and median concentrations in oxycodone
      and hydrocodone related deaths were more than two times greater than those in non
      drug-related deaths.

PMID- 18334102
TI  - Investigation of the first deaths in the United Kingdom involving the detection
      and quantitation of the piperazines BZP and 3-TFMPP.
AB  - Piperazines such as 1-benzylpiperazine (BZP), 1-(3
      trifluromethylphenyl)piperazine (3-TFMPP), and 1-(3-chlorophenyl)piperazine (3
      CPP) have become recent drugs of abuse. With stimulant effects comparable to
      amphetamines but with a lower potency and differential global scheduling status,
      they have been sold as a supposed legal alternative to "Ecstasy". A few non-fatal
      and fatal cases where BZP has been detected have been published and typically
      involve other drugs. However, toxicity involving BZP alone has also been
      reported. No case data currently exist for 3-TFMPP. The toxicological situation
      is complicated by the existence of positional isomers of TFMPP and CPP. This
      paper includes ultraviolet (UV) and liquid chromatography-mass spectrometry data
      for these isomers and indicates an advantage in using UV spectra to distinguish
      the structures. Consequently, the presence of BZP and 3-TFMPP has been confirmed
      in three fatalities (road traffic deaths and a fatal fall), with two cases
      involving both drugs. These are the first reported cases of 3-TFMPP in postmortem
      fluid. In all cases, other drugs and/or ethanol were found. BZP was found at
      concentrations of 0.71, < 0.50, and 1.39 mg/L and 3-TFMPP was found at
      concentrations of 0.05 and 0.15 mg/L in postmortem blood. Concentrations were
      also measured in urine. Although BZP and 3-TFMPP were not the direct cause of
      death, the toxicological findings presented in this paper may assist the
      interpretation of future cases involving these drugs where their significance may
      be more apparent.

PMID- 18334103
TI  - CYP2D6 ultrarapid metabolism and morphine/codeine ratios in blood: was it codeine
      or heroin?
AB  - The concentration ratio of morphine (Mor) over codeine (Cod) in opiate positive
      blood samples is used to discriminate between the use of illegal heroin (high
      ratios) and therapeutic codeine (low ratios). However, genetically caused CYP2D6
      ultra-rapid metabolism might lead to Mor/Cod comparable to heroin intake. A
      single oral dose of 30 mg codeine was administered to 11 CYP2D6 ultrarapid
      metabolizers (UMs) and 12 extensive metabolizers (EMs). Codeine and its morphine
      metabolites and Mor/Cod were quantified in plasma and urine by liquid
      chromatography with tandem mass spectrometry within 24 h after codeine intake.
      The Mor/Cod in plasma were below 1 for both UMs and EMs during the first 12 h.
      After 12 h, 9% of the 11 UM and none of the 12 EM had ratios > 1. In urine,
      Mor/Cod ratios were below one for all EMs and UMs during the first 12 h. Thus,
      CYP2D6 genotyping in general will not explain Mor/Cod ratios > 1 in plasma or
      urine, unless the time of drug intake is more than 24 h previous.

PMID- 18334104
TI  - An unusual trichloroethanol fatality attributed to sniffing trichloroethylene.
AB  - We report the death of a 28-year-old man due to sniffing a contact cement
      containing trichloroethylene. Initial testing revealed the presence of 80 mg/L
      trichloroethanol in cardiac blood, and the death was ruled as being due to
      trichloroethanol toxicity resulting from chloral hydrate ingestion. However,
      further investigation of the case revealed that the trichloroethanol resulted
      from trichloroethylene abuse. Subsequent targeted analysis for trichloroethylene,
      four months after the death, confirmed its presence in cardiac blood (1.1 mg/L),
      bile (4.5 mg/L), and liver (2.5 mg/kg). Trichloroethanol was initially detected
      during routine drug screening that employed gas chromatography (GC) using an HP-5
      column with electron capture detection and subsequently quantitated by GC using
      the same column as for the initial screen, but with flame-ionization detection
      (FID); ethchlorvynol was the internal standard. Trichloroethylene was quantitated
      by headspace GC with a Restek Rtx-BAC1 column and FID; 1,1,1-trichloroethane was
      the internal standard.

PMID- 18334105
TI  - A fatal intoxication from ingestion of 2-methyl-4-chlorophenoxyacetic acid
      (MCPA).
AB  - We report a fatal intoxication case by the ingestion of an herbicide, 2-methyl-4
      chlorophenoxyacetic acid (MCPA). A 23-year-old male was found dead in his car.
      The forensic autopsy revealed no remarkable morphological changes. However, in a
      toxicological screening test, MCPA was qualitatively detected from the extracts
      of stomach contents. Then MCPA in the extract of each body fluid and organ tissue
      was determined by gas chromatography-mass spectrometry with trimethylsilyl
      derivatization as follows (microg/g): 888.3 in the heart blood, 578.1 in the
      peripheral blood, 52.2 in the urine, 770.9 in the brain, 1362 in the right lung,
      1135 in the liver, 755.5 in the right kidney, and 10,200 in the stomach contents.
      These data strongly suggested that the male orally ingested MCPA. Moreover, p
      chloro-o-cresol (4-chloro-2-methylphenol) was also determined in the body fluids
      and organ tissues, suggesting a metabolite of MCPA. From these toxicological
      data, together with autopsy findings, the cause of his death was diagnosed as
      acute MCPA poisoning.

PMID- 18334106
TI  - A fatal case of bupropion (Zyban) overdose.
AB  - A sensitive and reproducible method for the identification and the quantitative
      determination of bupropion (BUP) and its major metabolites, hydroxybupropion (OH
      BUP) and threohydrobupropion (T-BUP), was developed in blood and urine. The three
      compounds were extracted with a solid-phase extraction procedure followed by LC
      ESI-MS-MS separation and quantification using decadeuterated lidocaine as
      internal standard. BUP and its metabolites were satisfactorily identified by
      multiple reactions monitoring detection. The limits of detection and
      quantification were determined at 5 and 10 microg/L, respectively, for each
      analyte. The intraday and interday coefficients of variability were lower than
      11.9% for BUP and its metabolites. This method was applied to the forensic case
      of a 35-year-old male who died after a suspected ingestion of 30 slow-release
      tablets of Zyban. As samplings were performed at least 72 h after the drug
      intake, BUP had disappeared from blood, but OH-BUP and T-BUP were present at the
      concentrations of 5.8 and 30.4 mg/L, respectively. In urine, concentrations
      ranged from 42.9 mg/L for BUP to 617 mg/L for T-BUP. These results agree with the
      hypothesis of a successful suicide attempt.

PMID- 18334107
TI  - Elimination half-lives of benzoylecgonine and MDMA in an apprehended driver.

PMID- 18334108
TI  - [Cancer incidence and mortality in Guangzhou City from 2000 to 2002].
AB  - BACKGROUND & OBJECTIVE: Population-based cancer registration has never been
      carried out before in Guangzhou. This study was to analyze the cancer incidence
      and mortality in Guangzhou and to provide references for prevention and treatment
      of cancer. METHODS: Data of cancer incidence and mortality during 2000--2002 were
      collected from Guangzhou Population-based Cancer Registry. Cancer incidence and
      mortality were calculated and analyzed. RESULTS: The crude cancer incidence
      during 2000--2002 in Guangzhou was 227.7 per 100,000 (257.0 per 100,000 in males
      and 196.5 per 100,000 in females)u the crude cancer mortality was 147.9 per
      100,000 (183.6 per 100,000 in males and 109.7 per 100,000 in females). The
      incidence of lung cancer ranked first followed by those of liver cancer,
      nasopharyngeal cancer, gastric cancer and colon cancer in males. Breast cancer
      was the leading cancer in females followed by those of lung cancer, liver cancer,
      colon cancer and nasopharyngeal cancer. The cancer incidence and mortality
      increased with age. CONCLUSION: Cancer incidence is high in Guangzhou, and the
      research for prevention and treatment of cancer should be enhanced.

PMID- 18334109
TI  - [Functions of V-val subtype of Epstein-Barr nuclear antigen 1].
AB  - BACKGROUND & OBJECTIVE: Epstein-Barr viral nuclear antigen 1 (EBNA1) plays a
      crucial role in the latency of Epstein-Barr virus (EBV). A close relation of V
      val subtype of EBNA1 with nasopharyngeal carcinoma (NPC) was suggested by its
      preference to infect NPC cells. This study was to investigate the functional
      difference between prototype and V-val EBNA1 in epithelial cell line HEK293.
      METHODS: The coding sequences of prototype and V-val EBNA1 were amplified by
      polymerase chain reaction and cloned into pGFP vector, then transfected into
      HEK293 cells respectively. The biological consequences of EBNA1 gene expression
      were examined. The transcriptional activation ability was compared between
      prototype and V-val subtype of EBNA1 using luciferase reporter system containing
      family of repeats (FR) sequence of EBV. RESULTS: Prototype and V-val EBNA1 showed
      no effect on cell proliferation, while the cloning efficiency of prototype EBNA1
      expressing cells was obviously lower than that of V-val EBNA1-expressing cells.
      No tumor formed in nude mice after injection of prototype or V-val EBNA1
      trasfected HEK293 cells. However, the luciferase activity was significantly
      higher in V-val EBNA1-expressing HEK293 cells than in prototype EBNA1-expressing
      HEK293 cells in transient transfection assay. CONCLUSION: Prototype and V-val
      EBNA1 have no direct transforming activity on cells, whereas the transactivation
      activity of V-val EBNA1 in FR-containing plasmid is significantly higher than
      that of prototype EBNA1.

PMID- 18334110
TI  - Circadian variation of plasma cortisol and whole blood reduced glutathione levels
      in nasopharyngeal carcinoma patients.
AB  - BACKGROUND & OBJECTIVE: Glutathione is involved in cellular protection against
      radiation damage and drug detoxification. This study was to investigate the
      circadian variation of plasma cortisol and whole blood reduced glutathione (GSH)
      levels in nasopharyngeal carcinoma (NPC) patients to provide references for
      chronotherapy for NPC. METHODS: A total of 13 NPC patients and 14 healthy
      volunteers were involved. Peripheral venous blood was sampled every 4 h during
      one 24-hour period starting at 12:00 am. The plasma cortisol concentration was
      determined by radioimmunoassay; the GSH concentration was determined by high
      performance liquid chromatography. RESULTS: Plasma cortisol levels of both groups
      displayed clear and similar circadian rhythms. The cortisol level peaked in both
      groups in the morning and was the lowest at mid-night. In both groups, GSH
      concentrations showed significant differences according to sampling time (ANOVA
      for Repeated Measures, F=5.18, P=0.02). By cosinor analysis, the circadian
      variation of the GSH level in NPC group was marginally statistically significant
      (Cosinor analysis, P=0.06) with the acrophase appeared at 05:02; the GSH level in
      control group displayed an obvious circadian rhythm and the acrophase appeared at
      07:44+/-01:56 (P<0.01). The rhythm-adjust mean value of glutathione was (19.60+/
      1.11) nmol/mg protein in NPC group and (8.95+/-0.46) nmol/mg protein in control
      group. CONCLUSIONS: The circadian rhythm of the plasma cortisol level is
      maintained in NPC patients, even in some patients at advanced stages. In NPC
      patients, GSH shows a trend of circadian variation which is similar to that in
      healthy controls. These results could be used to select special schedules for
      chrono-radiotherapy and chrono-chemotherapy for NPC patients.

PMID- 18334111
TI  - [Expression and significance of NKG2D ligands in 13 tumor cell lines].
AB  - BACKGROUND & OBJECTIVE: The interaction between NKG2D and its ligands plays a
      major role in immune surveillance against tumor. This study was to observe the
      expression and analyze the significance of NKG2D ligands in 13 tumor cell lines.
      METHODS: The mRNA expression of NKG2D ligands in K562, Raji, PG, Hep2, HepG2,
      HeLa, HT29, M21, MDA231, SGC7901, Caski, HL-60 and Jurkat cells was measured by
      reverse transcription-polymerase chain reaction (RT-PCR). The cytotoxicity of
      natural killer (NK) cells to the tumor cells at different effector-to-target cell
      (E:T) ratios were detected by MTT assay. The expression of MICA protein was
      measured by SABC immunohistochemistry and Western blot. RESULTS: The 13 tumor
      cell lines expressed different levels of NKG2D ligands. MICA was highly expressed
      in Hep2 cells, but not expressed in Caski, PG, HL-60 and Raji cells. The
      expression of MICA and MICB were positively correlated to the cytotoxicity of NK
      cells (r=0.851, P<0.001; r=0.652, P<0.05). Except for ULBP3, the expression of
      ULBP1, 2, 4 had no correlations to the cytotoxicity of NK cells. CONCLUSION:
      Among the 6 human NKG2D ligands, the expression of MICA is most intimate to the
      cytotoxicity of NK cells to tumor cells, and its expression level may determine
      the degree of immune response of NK cells to tumor.

PMID- 18334112
TI  - [125Iodine-induced radiation damage in the femoral arteries of rabbits].
AB  - BACKGROUND & OBJECTIVE: What damages 125Iodine (125I) seed implantation will do
      to normal tissue is an observation topic in clinic. This study was to investigate
      the impact of 125I seed implantation to the femoral arteries of rabbits. METHODS:
      A total of 30 healthy rabbits were divided into 3 groups. The femoral sheath in
      the hind leg at one side selected by random was opened and 10 125I seeds at 0.79
      0.85 mCi were implanted near the femoral artery according to the treatment
      planning system (TPS) before operation. In control group, 10 seeds without
      radioactivity were implanted. After 2 weeks, 2 months and 4 months, the rabbits
      were killed, the vessel wall nearest to the seeds was taken out and its
      morphologic changes were observed by gross examination, light microscopy and
      electron microscopy. RESULTS: In gross observation, the vessel segments of the
      legs with 125I seed implantation had no apparent abnormality. Under light
      microscope, a few exfoliative endothelial cells were observed. Under electron
      microscope, exfoliation of endothelial cells, degeneration of endothelial cells
      and smooth muscle cells were observed. The ratios of degenerative vessel
      endothelial cells to all vessel endothelial cells were 60%-70% in 2-week group,
      50% in 2-month group and 30% in 4-month group; the ratios of degenerative vessel
      smooth muscle cells to all vessel smooth muscle cells in the 3 groups were 50%,
      30% and 10%. CONCLUSION: 125I permanent implantation at 0.79-0.85 mCi mainly
      damages endothelial cells and smooth muscle cells of the normal vessels and this
      damnification is reversible.

PMID- 18334113
TI  - [Effects of survivin small interfering RNA on biological behaviors of bladder
      cancer T24 cells].
AB  - BACKGROUND & OBJECTIVE: Bladder cancer, a common tumor of urinary system, is
      related to genetic mutations that deregulate cell cycle and render tumor cells
      resistant to apoptosis. Survivin, a new member of the inhibitor-of-apoptosis
      (IAP) family, participates in the genesis of several human cancers, including
      bladder cancer, through inducing cell proliferation and inhibiting apoptosis.
      This study was to explore the effects of small interfering RNA (siRNA) targeting
      survivin on the biological behaviors of bladder cancer T24 cells. METHODS: A pair
      of survivin siRNA were designed and synthesized, and transfected into T24 cells
      with increasing concentrations (50-200 nmol/L) and injected in tumor-bearing mice
      at different doses (5 and 50 microg). The effects of survivin siRNA on the
      biological behaviors of T24 cells were assessed. RESULTS: Survivin siRNA
      efficiently down-regulated the expression of survivin mRNA. Its maximal effect
      was achieved at the concentration of 100 nmol/L, at which survivin expression
      level was down-regulated by 75.91%, the inhibition rate of cell proliferation was
      55.29% (P<0.01), and the apoptosis rate was significantly higher in siRNA
      transfected cells than in control cells (45.70% vs. 2.8%, P<0.01). Intratumoral
      injection of 50 microg survivin siRNA significantly inhibited the growth of
      bladder cancer in mice (P<0.01). CONCLUSIONS: Survivin siRNA could markedly
      inhibit survivin expression in T24 cells, induce cell apoptosis and inhibit the
      growth of transplanted tumor in mice. It might be a new gene therapy tool for
      bladder cancer.

PMID- 18334114
TI  - [Correlation of -31G/C polymorphisms of survivin promoter to tumorigenesis of
      gastric carcinoma].
AB  - BACKGROUND & OBJECTIVE: Survivin, a bifunctional protein that regulates cell
      division and suppresses apoptosis, may play an important role in tumorigenesis.
      This study was to determine the correlations of survivin gene 31-GC polymorphisms
      to the occurrence of gastric carcinoma and survivin mRNA expression. METHODS: The
      -31G/C single nucleotide polymorphism (SNP) of survivin promoter in peripheral
      blood samples from 96 gastric carcinoma patients and 67 healthy subjects was
      analyzed by polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP) and gene sequencing. Survivin mRNA expression in gastric carcinoma
      tissues was detected by real-time quantitative reverse transcription-polymerase
      chain reaction (RQ-RT-PCR). RESULTS: The genotype frequencies for -31G/G, -31G/C
      and -31C/C were 20.84%, 39.58% and 39.58% in gastric carcinoma patients, and
      46.26%, 41.80% and 11.94% in healthy subjects, respectively. The frequencies of
      survivin-31C allele and C/C genotype were significantly higher in gastric
      carcinoma patients than in healthy subjects [59.37% vs. 32.84%, Chi2 = 22.26,
      P<0.005, odds ratio (OR)=2.98, 95% confidence interval (CI)=1.96-4.51; 39.58% vs.
      11.94%, Chi2 =14.88, P<0.005, OR=4.83, 95% CI=2.91-8.03], but survivin mRNA was
      overexpressed with no significant difference in gastric cancer tissues subgrouped
      by genotypes. CONCLUSION: The -31C genotype of survivin promoter is associated
      with gastric cancer, and may be a risk factor of gastric carcinoma.

PMID- 18334115
TI  - [Proteinchip profiling of tumor markers in lung adenocarcinoma tissue from non
      smoking oriental female patients].
AB  - BACKGROUND & OBJECTIVE: Although lung cancer is largely attributable to tobacco
      smoking, more than half of the female patients with adenocarcinoma are non
      smokers in Hong Kong. This study dedicated to discover biomarkers for lung
      adenocarcinoma in non-smoking female patients with high-throughput proteinchip
      technology. METHODS: Protein profiles were generated from 29 specimens of primary
      lung cancers with matched adjacent non-cancer tissues using surface-enhanced
      laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS).
      RESULTS: Comparing the lung cancer and matched normal lung tissues from the non
      smoking female patients, 52 proteins with differential expression were
      discovered, with a percentage of difference ranging from 60% to 213% for the top
      ten biomarkers. Comparing the lung cancer tissues from the patients without
      smoking history and those with smoking history, 84 proteins with differential
      expression were found. The area under receiver operating characteristic curve
      (AUC) for the top ten biomarkers ranged from 0.82 to 0.89. Comparing lung cancer
      tissues from female and male patients, 69 proteins with differential expression
      were found. The AUC for the top ten biomarkers was ranged from 0.81 to 0.86.
      CONCLUSION: Using SELDI-TOF-MS, the biomarker candidates that are highly
      associated with non-smoking female patients with lung adenocarcinoma were
      filtered.

PMID- 18334116
TI  - [Serum proteomic spectra of esophageal squamous cell carcinoma patients analyzed
      with IMAC3 protein chip].
AB  - BACKGROUND & OBJECTIVE: Serum protein fingerprinting technology can help to
      identify the molecular changes related to esophageal carcinogenesis. This study
      was to screen serum markers and establish the predictive models that may be of
      help to serologic diagnosis of esophageal squamous cell carcinoma (ESCC).
      METHODS: Serum samples were collected from 68 ESCC patients and 44 age-and sex
      matched healthy subjects, and randomized into a training set (55 ESCC patients
      and 35 healthy subjects) and a blind testing set (13 ESCC patients and 9 healthy
      subjects). Serum samples were applied to immobilized metal affinity capture
      (IMAC3) proteinchip surfaces and tested by surface-enhanced laser
      desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS). The data
      were analyzed by Biomarker Wizard software to screen serum proteomic biomarkers.
      Decision classification tree models were established by bioinformatics. Double
      blind test was used to determine the sensitivity and specificity of the
      classification tree models. RESULTS: A total of 78 effective protein peaks were
      detected at the molecular range of 1.5 to 20 ku, among which 25 were
      significantly different between ESCC patients and healthy subjects (P<0.001). All
      the peptide pattern data were sampled randomly for 1,000 times using 3-cross
      validation approach, and 1,000 decision tree models were obtained. Twenty
      decision trees with the highest cross validation rate were chosen to construct
      the classification models which can differentiate ESCC patients from healthy
      subjects. With these decision trees, 18 samples were correctly forecasted from 22
      blind testing samples, with a sensitivity of 92.31% and a specificity of 66.67%.
      CONCLUSION: SELDI-TOF-MS technique combined with decision tree model can help to
      identify serum proteomic biomarkers related to ESCC and the predictive models can
      discriminate ESCC patients from healthy people effectively.

PMID- 18334117
TI  - [Application of SELDI-TOF serum proteome profiling in cervical squamous cell
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Up to now, there is no valid biomarker in early diagnosis
      of cervical cancer. Surface-enhanced laser desorption/ionization time-of-flight
      mass spectrometry (SELDI-TOF-MS) is a new technique used to identify biomarkers
      for cancers. This study was to screen new biomarkers and build diagnostic models
      for early diagnosis of cervical cancer by SELDI-TOF-MS. METHODS: SELDI-TOF-MS was
      used to detect the serum proteomic patterns of 91 patients with early stage
      cervical squamous cell carcinoma, 15 patients with cervical intraepithelial
      neoplasia III (CIN III), and 55 healthy women (control). The serum proteomic
      spectra were generated on weak cation exchange (WCX2) chips. Differences in
      protein peaks were analyzed using Biomarker Wizard software. The diagnostic model
      was built by Biomarker Patterns software and further valuated by a large-scale
      blind test. RESULTS: A total of 122 protein peaks were detected at the molecular
      range of 1.5 to 20 ku, among which 19 ones were significantly different between
      invasive cervical squamous cell carcinomas and controls (P<0.001). A diagnostic
      model consisting of 2 protein peaks at 3,977 m/z and 5,807 m/z was established.
      Its specificity was 83.78% (31/37) and its sensitivity was 97.29% (36/37). A
      sensitivity of 94.44% (51/54) and a specificity of 94.44% (17/18) in a large
      scale blind test were obtained. CONCLUSION: The diagnostic model consisting of 2
      protein peaks at 3,977 m/z and 5,807 m/z can discriminate cervical cancer
      patients from healthy women.

PMID- 18334118
TI  - [Effects of isatin on cell cycle arrest and apoptosis of neuroblastoma cell line
      SH-SY5Y].
AB  - BACKGROUND & OBJECTIVE: Isatin (ISA) is a natural material that exists in
      mammalian body fluids and tissues. ISA could inhibit the growth of tumors, but
      the mechanism remains unclear. This study aimed to explore the effects of ISA on
      the cell cycle and apoptosis of neuroblastoma cell line SH-SY5Y. METHODS:
      Fluorescent staining, flow cytometry, and Western blot were performed to analyze
      the cell cycle arrest and apoptosis of SH-SY5Y cells after treatment of ISA at
      different concentrations (0, 100, 200, 400 micromol/L). RESULTS: When treated
      with 400 micromol/L ISA for 48 h, SH-SY5Y cells showed typical apoptotic
      morphologic changes including chromatin condensation and DNA fragment. Along with
      the increase of ISA concentration, Bcl-2 expression was decreased, the ratio of
      Bcl-2 to Bax was significantly decreased (P<0.05). When treated with ISA (100,
      200, 400 micromol/L) for 48 h, the positive rates of activated Caspase-3 in SH
      SY5Y cells were significantly higher than that in control SH-SY5Y cells (19.28%,
      25.88%, and 33.43% vs. 10.58%, P<0.05). Moreover, inhibitor of caspase-activated
      DNase (ICAD), the substrate of Caspase-3, was degraded. In addition, the
      proportion of SH-SY5Y cells at G1 phase was significantly increased with an
      apparent G1 phase arrest when treated with ISA (100, 200, 400 micromol/L) for 48
      h. In the progress of cell cycle arrest induced by ISA, phosphorylated ERK and
      CDK1 expression were down-regulated (P<0.05). CONCLUSION: ISA can induce
      apoptosis and G1 phase arrest in SH-SY5Y cells, possibly by decreasing Bcl-2/Bax,
      activating Caspase-3 and down-regulating the expression of phosphorylated ERK and
      CDK1.

PMID- 18334119
TI  - [Clinical characteristics and prognosis of aged nasopharyngeal carcinoma
      patients: a report of 313 cases].
AB  - BACKGROUND & OBJECTIVE: Although there are many multi-center, large sample sized,
      randomized prospective or retrospective studies, most aged nasopharyngeal
      carcinoma (NPC) patients were excluded from these studies. This study was to
      explore clinical characteristics and prognoses of aged NPC patients. METHODS:
      Clinical data of 313 NPC patients older than 60 years, hospitalized in the
      Department of Nasopharyngeal Carcinoma of Cancer Center of Sun Yat-sen University
      from Jan. 1, 1998 to Dec. 31, 2001, were analyzed. Of the 313 patients, 265 were
      men and 48 were women; 295 patients received radiotherapy, 91 of which received
      chemotherapy; 18 patients received chemotherapy alone or no treatment. The
      survival rate was calculated by Kaplan-Meier method, and compared by log-rank
      test. Prognosis was analyzed by Cox regression model. RESULTS: The 1-, 3-, and 5
      year overall survival (OS) rates and cancer-specific survival (CSS) rates of the
      295 aged NPC patients underwent radiotherapy were 77.0%, 58.0%, 48.0% and 78.0%,
      60.0%, 53.0%, respectively. Clinical stage, T stage, N stage, involvement of the
      skull base, cranial nerve invasion, radiation dose on the nasopharynx,
      radiotherapeutic field and interval time were significant prognostic factors of
      survival(P<0.05), whereas only clinical stage was independent prognostic
      factor(P<0.01). Chemotherapy did not influent the prognosis of aged NPC patients
      (P=0.42). CONCLUSIONS: Radiotherapy is an effective way to cure aged NPC
      patients, while chemotherapy can not improve the efficacy. '92 Fuzhou staging can
      predict prognosis of aged NPC patients properly. Elderly NPC patients have worse
      survival rates than non-aged ones.

PMID- 18334120
TI  - [Long-term efficacy of prophylactic upper neck irradiation for stage N0
      nasopharyngeal carcinoma].
AB  - BACKGROUND & OBJECTIVE: Whether prophylactic irradiation should cover the whole
      neck or just the upper neck for nasopharyngeal carcinoma (NPC) patients, without
      neck lymph node metastasis (N0), remains controversial. This study was to assess
      the rationality of prophylactic upper neck irradiation for stage N0 NPC patients.
      METHODS: Clinical data of 432 stage N0 NPC patients were analyzed. All patients
      were treated with radical radiotherapy alone. The extent of prophylactic
      irradiation was limited to the upper neck of the patients. Median radiation doses
      were 70 Gy for the primary tumors, and 50 Gy for the upper necks. Kaplan-Meier
      method was used to analyze survival rates and neck recurrence rates. Log-rank
      test was used to compare neck recurrence rates in patients with or without
      nasopharyngeal recurrence. Cox proportional hazards model was used to evaluate
      the prognostic factors for neck control. RESULTS: Seventeen out of 432 patients
      had neck recurrence. The 5-year control rate of the neck was 96.06%. Among the 17
      patients with neck recurrence, 6 had concurrent nasopharyngeal relapse. The
      occurrence rates of neck recurrence alone were 0.93%(4/432) in the upper necks
      and 1.62% (7/432) in the lower necks (P=0.937). The neck recurrence rates were
      9.52% (6/63) and 2.98% (11/369) in patients with and without nasopharyngeal
      recurrence, respectively (P=0.002). Nasopharyngeal recurrence was the only
      independent prognostic factor for neck control. CONCLUSION: The overall neck
      recurrence rate is low for stage N0 NPC patients after receiving irradiation.
      Prophylactic upper neck irradiation is reasonable for stage N0 NPC patients.

PMID- 18334121
TI  - [Surgical treatment and long-term efficacy on stage T1-3N0 differentiated thyroid
      carcinoma].
AB  - BACKGROUND & OBJECTIVE: Whether to choose total thyroidectomy or lobectomy for
      the primary lesion of differentiated thyroid carcinoma (DTC) limited in one lobe
      is controversial. This study was to investigate the patterns of surgical
      treatment for stage T1-3N0 DTC, and observe the long-term efficacy. METHODS:
      Clinical data of 153 DTC patients, first treated at Cancer Center of Sun Yat-sen
      University from 1985 to 2000, were reviewed. The postoperative pathologic stage
      of these patients was T1-3N0. The multiple centricity of primary lesions,
      patterns of surgical treatment, and prognosis were analyzed. RESULTS: Of the 153
      DTC patients, 21 had cancer multifocality: 12 had multiple cancer foci in one
      lobe and 9 had cancer multifocality in both lobes. Ninety-two patients received
      unilateral lobectomy plus isthmectomy; 44 patients received ipsilateral subtotal
      lobectomy plus isthmectomy. Among the 9 patients who had cancer multifocality in
      both lobes, 7 received unilateral lobectomy plus isthmectomy with contralateral
      subtotal lobectmoy and 2 received bilateral subtotal lobectomy. Eight patients,
      whose primary lesions were at isthmus, underwent isthmectomy plus bilateral
      partial lobectomy. Regional lymph node metastasis appeared in 7 patients after
      initial operation: 6 in the neck and 1 in the upper mediastinum. Five patients
      had distant metastasis after operation. The 5-, 10-and 15-year survival rates of
      these 153 patients were 98.7%, 96.1% and 86.9%, respectively. Age, pathologic
      type, tumor size and distant metastasis affected the survival (P<0.05). The
      patients whose age was less than 45 years, tumor size was less than 4 cm,
      pathologic type was papillary or mixed carcinoma, and who had no distant
      metastasis had relatively good prognosis. Age and distant metastasis were
      independent prognostic factors. CONCLUSIONS: It is feasible to perform unilateral
      lobectomy or subtotal lobectomy plus isthmectomy for patients with stage T1-3N0
      DTC. The long-term outcomes of stage T1-3N0 DTC patients are relatively well.
      Age, pathologic type, tumor size and distant metastasis affect prognosis.

PMID- 18334122
TI  - [Application of central lymph node dissection to surgical operation for clinical
      stage n0 papillary thyroid carcinoma].
AB  - BACKGROUND & OBJECTIVE: The treatment for papillary thyroid carcinoma (PTC)
      without cervical lymph node metastasis (cN0) is controversial. This study was to
      explore a suitable method to dissect cervical lymph nodes for stage cN0 PTC
      patients. METHODS: Eighty-four stage cN0 PTC patients, diagnosed by B ultrasound
      or cervical MRI from 2005--2006, were randomly divided into two groups.
      Thyroidectomy and ipsilateral central lymph node dissection were performed in
      Group A, while only thyroidectomy was performed in Group B. Each group contained
      42 patients. Both groups took thyroxin tablets after operation. RESULTS: An
      average of 3 lymph nodes were found in each case of Group A, and the lymph node
      metastasis rate was 47.62%. The occurrence rates of complications were not
      significantly different between the two groups (P<0.05). CONCLUSIONS:
      Thyroidectomy plus ipsilateral central lymph node dissection is recommended for
      the treatment of stage cN0 PTC. It can also avoid damage of recurrent laryngeal
      nerve in re-dissection.

PMID- 18334123
TI  - [Treatment and prognosis of gingival carcinoma: a report of 116 cases].
AB  - BACKGROUND & OBJECTIVE: The treatment and prognosis of gingival carcinoma, a
      common oral carcinoma, have seldom been reported. This study was to explore
      appropriate therapies and analyze prognostic factors of gingival carcinoma.
      METHODS: Clinical data of 116 gingival carcinoma patients, treated at Cancer
      Center of Sun Yat-sen University from 1992 to 2003, were analyzed. Survival
      analyses were performed for patients who received surgery, radiotherapy, or
      surgery combined with chemotherapy or/and radiotherapy. The patients had been
      followed up for more than 3 years. RESULTS: One hundred patients received radical
      therapy. The overall 3-and 5-year survival rates were 52.7% and 41.8%. The 5-year
      survival rates were 50.3% in surgery alone group and 49.0% in combined treatment
      group, without significant difference. The 5-year survival rate of radiotherapy
      alone group was only 20.0%. For advanced gingival carcinoma, the recurrence rate
      was much lower in combined treatment group than in surgery alone group. Clinical
      stage and surgical margin status were predictors of survival. CONCLUSIONS:
      Surgery alone is appropriate for gingival carcinoma patients at an early stage;
      surgery combined with chemotherapy or/and radiotherapy is an adequate treatment
      for patients at advanced stages. Clinical stage and surgical margin status are
      important prognostic factors.

PMID- 18334124
TI  - [Childhood thyroid carcinoma: clinical analyses of 22 cases].
AB  - BACKGROUND & OBJECTIVE: Thyroid carcinoma is rarely occurred in children.
      Clinicopathologic characteristics, therapy and prognosis of childhood thyroid
      carcinoma patients are different from those of adult patients, and the treatment
      of this disease is controversial. This study was to explore the clinicopathologic
      characteristics, diagnosis and therapy of thyroid carcinoma in children. METHODS:
      Clinical data of 22 children under the age of 14, diagnosed as thyroid carcinoma
      between Jan. 1980 and Dec. 2000, were reviewed. RESULTS: According to UICC
      clinical and histopathologic classification(2002), 19 cases were classified as
      stageI (2 cases of T1-4N0M0 and 17 cases of T1-4N1M0) and 3 cases as stage II (T1
      4N1-4M1). Of the 22 patients, 8 (36.4%) had papillary carcinoma, 8 (36.4%) had
      follicular carcinoma, 5(22.7%) had mixed papillary-follicular carcinoma, and 1
      (4.5%) had medullary carcinoma. All patients had received operation and
      postoperative thyroxin therapy. Unilateral and bilateral neck dissection had been
      performed in 12 and 7 patients, respectively; 19 patients had cervical lymph node
      metastasis. The follow-up period was 6 to 26 years (median, 14.83 years). The 5
      and 10-year survival rates were 100% and 95.5%, respectively. CONCLUSIONS:
      Childhood thyroid carcinomas are mostly differentiated carcinomas, with high
      frequency of cervical lymph node metastases. The optimal treatment for thyroid
      carcinoma in children may improve the quality of life and decrease the incidence
      of complications.

PMID- 18334125
TI  - [Local Castleman's disease: a report of 17 cases with literature review].
AB  - BACKGROUND & OBJECTIVE: Castleman's disease (CD), also named angiofollicular
      lymph node hyperplasia or giant lymph node hyperplasia, is an uncommon reactive
      lymphadenopathy with unknown causes. This study was to report clinical features
      and therapeutic outcomes of 17 cases of local Castleman's disease (LCD), review
      literatures to improve the diagnosis and management of CD. METHODS: Clinical data
      of 17 LCD patients, treated in Cancer Center of Sun Yat-sen University from Aug.
      1995 to Jul. 2006, were reviewed. RESULTS: There were 3 cases with and 14 cases
      without clinical symptoms. A single lymph node or aggregation of multiple lymph
      nodes was observed in a single location. The longest diameters of involved lymph
      nodes ranged from 1.2 to 10.4 cm. The lesions were located in the neck (11
      cases), mediastinum (3 cases), lung (1 case), mesentery (1 case), adrenal region
      (1 case). Fifteen cases were hyaline vascular type, 1 case was plasma cell type
      and 1 case was mixed type; all were confirmed pathologically. One hyaline
      vascular type LCD patient had splenomegaly, hypoalbumin (25.6 g/L), hyperglobulin
      (80.0 g/L) and positive fecal occult blood. One plasma cell type LCD patient had
      anemia (95.0 g/L), positive urine protein and positive fecal occult blood. The
      other 15 patients had normal laboratory results. All patients underwent complete
      surgical resection. The duration of follow-up ranged from 1 to 129 months with a
      median of 25 months. Fifteen followed-up patients were all alive without
      recurrence. CONCLUSIONS: LCD patients mainly have lymphadenectasis in a single
      location, no clinical symptoms and normal laboratory results, with a majority of
      hyaline vascular type. Although CT is helpful for the diagnosis of LCD, the final
      diagnosis depends on pathologic examination. LCD patients can live long without
      recurrence after complete surgical resection of the tumor.

PMID- 18334126
TI  - [Efficacy of pulmonary resection for primary hepatocellular carcinoma patients
      with pulmonary metastasis].
AB  - BACKGROUND & OBJECTIVE: Pulmonary resection is considered as an active therapy
      for malignant tumor patients with pulmonary metastasis. This study was to
      evaluate the efficacy of pulmonary resection for primary hepatocellular carcinoma
      (HCC) patients with pulmonary metastasis. METHODS: Clinicpathologic data and
      outcomes of 12 HCC patients underwent pulmonary resection due to pulmonary
      metastasis were analyzed. RESULTS: Among the 12 patients, 9 had 1 or 2 pulmonary
      metastases, 1 of which had relapsed pulmonary metastasis after the first
      pulmonary resection; the other 3 patients who had 3 or more pulmonary metastases
      all recurred with pulmonary metastasis after the first pulmonary resection. The
      median survival time was 52 months after the first hepatectomy and 24 months
      after the first pulmonary resection. The overall 1-, 3-and 5-year survival rates
      were 100.0%,75.0% and 47.3% after the first hepatectomy, and 83.3%, 46.7% and
      21.0% after the first pulmonary resection, respectively. CONCLUSION: When
      intrahepatic recurrence is effectively controlled, HCC patients with 1 or 2
      pulmonary metastases might benefit from pulmonary resection and achieve prolonged
      survival.

PMID- 18334127
TI  - [Expression and clinical significance of EMS1 gene in gastric carcinoma].
AB  - BACKGROUND & OBJECTIVE: EMS1 (chromosome eleven, band q13, mammary tumor and
      squamous cell carcinoma-associated gene 1) is correlated to the genesis,
      progression, invasion and metastasis of some malignancies. This study was to
      investigate the expression of EMS1 protein in gastric carcinoma, and to explore
      its correlation to the carcinogenesis of gastric carcinoma. METHODS: The
      expression of EMS1 protein in 20 specimens of normal gastric mucosa, 38 specimens
      of intraepithelial neoplasia, and 146 specimens of gastric carcinoma was detected
      by immunohistochemistry. RESULTS: EMS1 protein was expressed in cytoplasm. The
      positive rate of EMS1 protein was significantly higher in gastric carcinoma than
      in intraepithelial neoplasia and normal gastric mucosa (89.7% vs. 68.4% and
      20.0%, P<0.001), and significantly higher in intraepithelial neoplasia than in
      normal gastric mucosa (P<0.001). The positive rate of EMS1 protein was
      significantly lower in the gastric carcinomas at early stages than in those at
      advanced stages (60.9% vs. 95.1%, P<0.001), and significantly higher in the
      gastric carcinomas with lymph node metastases than in those without lymph node
      metastases (96.8% vs. 77.0%, P<0.001). EMS1 protein expression had no
      correlations to sex, age, tumor differentiation and diameter. CONCLUSION: EMS1
      protein expression is related to the carcinogenesis, lymph node metastasis and
      clinical stage of gastric carcinoma.

PMID- 18334128
TI  - [Influence of patient setup error on planning risk volumes for nasopharyngeal
      carcinoma patients receiving intensity-modulated radiation therapy].
AB  - BACKGROUND & OBJECTIVE: Determination of planning risk volumes (PRVs) for an
      organ at risk greatly affects dose optimization in designing the intensity
      modulated radiation therapy (IMRT) regimen. Patient setup errors have been found
      to closely correlate to the definition of PRVs. This study was to investigate the
      safety margin for the organ at risk during IMRT planning for nasopharyngeal
      carcinoma (NPC) patients. METHODS: Nineteen NPC patients (stage T1-2N0M0) who
      received IMRT for the first time were studied. Repeated computed tomography (CT)
      scans were performed for the patients once a week during the whole treatment
      course. A total of 85 CT scan reports were obtained. Differences between patient
      positioning of each time and first treatment setup were caluculated by comparing
      the anatomical landmarks (that is, optical nerve, pituitary, spine, and parotid)
      on each CT scan image using Osiris software. RESULTS: The displacement of optical
      nerve and pituitary in X, Y, and Z directions were, in absolute values, (0.86+/
      0.53) mm, (0.84+/-0.68) mm, and (0.93+/-1.02)mm, respectively. The standard
      deviations (SDs) of systematic errors for the axial vector displacement were 0.83
      mm, 1.08 mm, and 1.21 mm, while the SDs of random errors were 0.85 mm, 0.83 mm
      and 1.14 mm. The displacement of spine and parotid in X, Y, and Z directions
      were, in absolute values, (0.98+/-0.74) mm, (1.25+/-0.88) mm, and (1.43+/-1.02)
      mm, respectively. The SDs of systematic errors for axial vector displacement were
      0.98 mm, 1.35 mm, and 1.87 mm, while the SDs of random errors were 1.02 mm, 1.46
      mm, and 1.54 mm. CONCLUSION: It is feasible to determine the size of a safety
      margin of IMRT for organs at risk using repeated CT scans for NPC patients.

PMID- 18334129
TI  - [Correlation of PI3K-Akt signal pathway to apoptosis of tumor cells].
AB  - PI3K-Akt signal pathway is an important intracellular signal transduction
      pathway. It plays important roles in cell apoptosis and survival by affecting the
      activity of downstream effector molecules, and it is closely associated with the
      development and progression of human tumors, therefore, PI3K and Akt might be
      potential targets for tumor therapy. This article reviewed recent progress on the
      composition, function, regulation and anti-apoptosis of PI3K-Akt signal pathway,
      and discussed its potential application to tumor gene therapy.

PMID- 18334131
TI  - Treatment options for Duchenne muscular dystrophy.
AB  - The main goal in the treatment of Duchenne muscular dystrophy (DMD) is to
      maintain ambulation for as long as possible and to anticipate and manage the
      associated complications, such as joint contractures, scoliosis, cardiomyopathy,
      respiratory insufficiency, and weight gain. Cognitive and behavioral symptoms
      occur in about one third of patients, and it is important to recognize and manage
      them promptly, developing an individualized plan at school and at home to
      maximize the patient's cognitive abilities. In the late phase of the disease,
      palliative care is of paramount importance. Corticosteroid therapy (prednisone
      and deflazacort) is the only effective pharmacologic treatment for DMD. Daily
      prednisone treatment increases muscle strength and function, improves pulmonary
      function, and significantly slows the progression of weakness. Deflazacort has a
      similar effect on muscle strength, but it is not available in the United States.
      Treatment with corticosteroid should be offered to all patients with DMD, but the
      beneficial effects and potential adverse effects should be fully discussed before
      treatment begins. The optimal dose of prednisone is 0.75 mg/kg per day, up to a
      maximum of 40 mg/d. If adverse effects occur, a decrease in dosage is
      appropriate. Monitoring of muscle function and adverse effects by a neurologist
      or neuromuscular specialist is strongly recommended. Physical and occupational
      therapists should be involved early in the treatment of patients with DMD to
      develop a program that includes heel cord stretching and exercise. In the later
      phases, these therapists can recommend adaptive equipment and maximize
      independence. Orthopedic consultation is important in monitoring and managing
      scoliosis and joint contractures in the nonambulatory phase of the disease.
      Pulmonary evaluation for ventilatory care is important; pulmonary consultation is
      essential when vital capacity declines. The use of assistive cough devices, nasal
      bilevel positive airway pressure, and tracheostomy must be discussed with
      patients and their families. For all patients with DMD, particularly those
      receiving prednisone, consultation with a dietitian is very helpful to control
      weight and maintain a healthy diet.

PMID- 18334130
TI  - Management of symptoms in amyotrophic lateral sclerosis.
AB  - The mainstay of treatment of amyotrophic lateral sclerosis (ALS) is management of
      symptoms. Health care providers involved in the care of ALS patients should be
      armed with the most current knowledge about symptomatic management of these
      patients so that an aggressive approach to controlling symptoms can be undertaken
      at the most appropriate time. Among the important modalities is noninvasive
      positive pressure ventilation, which has been shown to improve not only quality
      of life but also survival. Similarly, clinicians should consider earlier
      intervention with enteral feeding. Palliative care should begin soon after ALS is
      diagnosed.

PMID- 18334132
TI  - Charcot-Marie-Tooth disease.
AB  - The family of hereditary peripheral neuropathies that makes up Charcot-Marie
      Tooth disease (CMT) comprises some of the most common neuromuscular disorders.
      Over the past decade, understanding of the molecular basis of CMT has increased
      enormously. In addition, the neurophysiologic deficits and clinical problems
      associated with CMT are more clearly delineated, and the precise genetic cause of
      many types of CMT has now been determined. Advances in molecular biology and
      genetic manipulation techniques have allowed the development of animal models of
      some of these CMT types, allowing more productive scientific exploration of
      possible treatments. Recent treatment advances that have been effective in animal
      models include oral supplementation with curcumin and vitamin C (ascorbic acid),
      and the use of onapristone, a progesterone antagonist. Human trials with vitamin
      C are currently in progress. While ongoing molecular genetic research continues
      to identify more of the mutant genes and proteins that cause the various disease
      subtypes, clinical research should continue to focus on developing pharmaceutical
      and rehabilitative therapies to ameliorate nerve degeneration and ultimately
      improve function for patients with CMT. These patients optimally should be
      managed in a comprehensive, multidisciplinary setting involving neurologists,
      physiatrists, orthopedic surgeons, physical and occupational therapists, and
      orthotists. Treatment should be aimed at maximizing independence and quality of
      life.

PMID- 18334133
TI  - Diagnosis and treatment of multifocal motor neuropathy.
AB  - Multifocal motor neuropathy (MMN) is a unique disease mimicking motor neuron
      disease, but it is treatable with intravenous immunoglobulins. Anti-GM1 IgM
      antibody titers are not sensitive enough to predict the outcome. Electrodiagnosis
      is essential for the diagnosis of MMN. Conduction block has been suggested as the
      best diagnostic marker, but it is not found in all treatable cases. Activity
      dependent conduction changes, as revealed by comparing conduction before and
      after maximal voluntary contraction of the muscle, are a convenient and promising
      tool. Treatment options include various immunosuppressants (including
      cyclophosphamide), but there has not been ample evidence in favor of any of these
      agents in randomized controlled trials. Intravenous immunoglobulins remain the
      mainstay for treating MMN.

PMID- 18334134
TI  - Sedation in the neurologic intensive care unit.
AB  - Providing adequate sedation in the neurologic intensive care unit (ICU) depends
      on determination of proper goals for sedation, adequate assessment of the level
      of sedation, and appropriate choice of drug based on the patient's physiology.
      The management of sedation in the ICU will influence long-term outcome. Delirium,
      anxiety, and pain must be identified and treated separately. The use of protocols
      can improve compliance with published evidence-based recommendations. Propofol
      and dexmedetomidine may be used for rapidly titratable sedation, benzodiazepines
      for anxiolysis, neuroleptics for treatment of delirium, and opiates for
      analgesia. Unique aspects of patients with acute brain disease, such as elevated
      intracranial pressure or status epilepticus, require adaptation of sedative
      regimens. Processed EEG monitoring and volatile anesthetic agents have not yet
      proven beneficial or practical for use in the ICU.

PMID- 18334135
TI  - Acute treatment of cerebral venous and dural sinus thrombosis.
AB  - Management of thrombosis of the dural sinus and cerebral veins (CVT) includes
      treatment of the underlying condition, antithrombotic treatment, symptomatic
      treatment, and the prevention or treatment of complications. Intravenous heparin
      or subcutaneous low-molecular-weight heparin should be used in acute CVT to
      prevent thrombus propagation and pulmonary embolism and to increase the chances
      of recanalization. Anticoagulation is safe and can be used in patients with acute
      CVT who have intracranial hemorrhagic lesions. Endovascular thrombolysis (with or
      without mechanical thrombus disruption) is an experimental treatment to be used
      in experienced centers for severe cases or patients who fail to improve on
      anticoagulation. Local thrombolysis is not useful in patients with large infarcts
      and impending herniation. In patients with severe headache and papilledema,
      intracranial hypertension can be reduced and symptoms relieved through a
      therapeutic lumbar puncture. Hemicraniectomy may be lifesaving in patients with
      parenchymal lesions leading to herniation. In patients with acute seizures and
      supratentorial lesions, antiepileptic drugs should be prescribed. Prophylactic
      use of these drugs can also be considered for patients with one of these risk
      factors but should be avoided in patients with neither of them. To reduce the
      risk of recurrent deep venous thrombosis of the limbs, vitamin K antagonists are
      given for a variable period depending on the patient's inherent risk of
      thrombosis, aiming at an International Normalized Ratio of 2 to 3.5. If CVT is
      related to a transient risk factor (eg, pregnancy, infection), we recommend
      anticoagulants for 3 months. In patients with idiopathic CVT or CVT associated
      with "mild" thrombophilia, the period of anticoagulation must be extended to 6 to
      12 months. In patients with "severe" thrombophilia (eg, two or more prothrombotic
      abnormalities or antiphospholipid syndrome), anticoagulants should be given for
      life. Patients with persistent symptoms of increased intracranial hypertension,
      visual loss, or both can be treated with repeated lumbar punctures or a
      lumboperitoneal shunt. For the prevention of remote seizures, antiepileptic drugs
      are recommended for patients with seizures in the acute phase and for those who
      experience a seizure after the acute phase. These drugs can also be considered
      for patients without seizures who have supratentorial hemorrhagic lesions or
      motor deficits.

PMID- 18334136
TI  - Treatment of cerebellar masses.
AB  - Cerebellar masses are a heterogenous group of conditions that can cause
      compression of the aqueduct or fourth ventricle, resulting in obstructive
      hydrocephalus, brainstem compression, and upward/downward herniation as a direct
      result of mass effect. Untreated lesions can be fatal in a few hours, but prompt
      and appropriate treatment of the mass effect can produce very good outcomes.
      These patients should be closely followed in a critical care setting that has
      rapid access to neurosurgical expertise. Medical measures to decrease brain edema
      should be taken, including elevation of the head of the bed and avoidance of hypo
      osmolar solutions, hypercarbia, or hyperthermia. Osmotic diuretics should be
      initiated promptly in patients with clinical worsening and radiographic evidence
      of edema resulting in mass effect. However, medical measures should not delay
      surgical intervention, which should proceed as rapidly as possible when
      indicated. Cerebellar hemorrhages more than 3 cm in diameter and cerebellar
      hemispheric strokes involving more than one third of the hemisphere should be
      considered for early suboccipital craniotomy with decompression. Regardless of
      lesion size, neurologic deterioration and radiologic signs of obstructive
      hydrocephalus should call for emergency decompressive surgery with resection of
      hematoma or necrotic brain tissue. Ventriculostomy should be considered as a
      bridge to surgical decompression, given the theoretical concern of upward
      herniation mediated by supratentorial drainage in the face of an underlying
      posterior fossa mass lesion. Steroids are not indicated for cerebrovascular
      disease but should be used to treat vasogenic edema induced by tumor.
      Anticoagulation is reserved for cerebellar venous and dural sinus thrombosis.
      Specific treatments targeting the underlying pathology should be used
      aggressively: thrombolysis and endovascular interventions for eligible stroke
      patients, antibiotic therapy for abscesses, and radiotherapy, chemotherapy, or
      both for tumors.

PMID- 18334137
TI  - Treatment of paroxysmal sympathetic hyperactivity.
AB  - Episodes of paroxysmal sympathetic hyperactivity, sometimes referred to as
      autonomic storms, are not uncommon in patients with severe traumatic brain
      injury. Their distinctive characteristics include fever, tachycardia,
      hypertension, tachypnea, hyperhidrosis, and dystonic posturing. The episodes may
      be induced by stimulation or may occur spontaneously. Their pathophysiology has
      not been fully elucidated, but the manifestations clearly indicate activation or
      disinhibition of sympathoexcitatory areas. These spells are often confused with
      seizures, leading to unnecessary treatment with antiepileptic drugs. General
      principles in the management of paroxysmal sympathetic hyperactivity include
      adequate hydration, exclusion of mimicking conditions (infection, pulmonary
      embolism, hydrocephalus, epilepsy), effective analgesia, and avoidance of
      triggers, when identified. The most useful pharmacologic agents are morphine
      sulfate and nonselective beta-blockers (eg, propranolol). Intrathecal baclofen
      may be effective in refractory cases. Bromocriptine and clonidine are helpful in
      some patients, but their efficacy is less consistent. Early recognition and
      adequate treatment of paroxysmal sympathetic hyperactivity is important to avoid
      prolongation of the patient's stay in the intensive care unit and to enable
      recovering patients to participate without restrictions in rehabilitation
      therapy.

PMID- 18334138
TI  - [CONSORT for reporting randomized controlled trials in journal and conference
      abstracts: explanation and elaboration].
AB  - BACKGROUND: Clear, transparent, and sufficiently detailed abstracts of
      conferences and journal articles related to randomized controlled trials (RCTs)
      are important, because readers often base their assessment of a trial solely on
      information in the abstract. Here, we extend the CONSORT (Consolidated Standards
      of Reporting Trials) Statement to develop a minimum list of essential items,
      which authors should consider when reporting the results of a RCT in any journal
      or conference abstract. METHODS AND FINDINGS: We generated a list of items from
      existing quality assessment tools and empirical evidence. A three-round, modified
      Delphi process was used to select items. In all, 109 participants were invited to
      participate in an electronic survey; the response rate was 61%. Survey results
      were presented at a meeting of the CONSORT Group in Montebello, Canada, January
      2007, involving 26 participants, including clinical trialists, statisticians,
      epidemiologists, and biomedical editors. Checklist items were discussed for
      eligibility into the final checklist. The checklist was then revised to ensure
      that it reflected discussions held during and subsequent to the meeting. CONSORT
      for Abstracts recommends that abstracts relating to RCTs have a structured
      format. Items should include details of trial objectives; trial design (e.g.,
      method of allocation, blinding/masking); trial participants (i.e., description,
      numbers randomized, and number analyzed); interventions intended for each
      randomized group and their impact on primary efficacy outcomes and harms; trial
      conclusions; trial registration name and number; and source of funding. We
      recommend the checklist be used in conjunction with this explanatory document,
      which includes examples of good reporting, rationale, and evidence, when
      available, for the inclusion of each item. CONCLUSIONS: CONSORT for Abstracts
      aims to improve reporting of abstracts of RCTs published in journal articles and
      conference proceedings. It will help authors of abstracts of these trials provide
      the detail and clarity needed by readers wishing to assess a trial's validity and
      the applicability of its results.

PMID- 18334139
TI  - [Improving the quality of reporting Chinese herbal medicine trials: an elaborated
      checklist].
AB  - Abstract: In order to improve the quality of reporting Chinese herbal medicine
      (CHM) trials, an elaborated checklist was developed according to the basic
      characteristics of traditional Chinese medicine (TCM) and on the basis of the
      Reporting Randomized Controlled Trials of Herbal Interventions: An Elaborated
      CONSORT Statement. This checklist adopted the 22 items of the Herbal CONSORT
      Statement with some necessary elaboration and modification in the detailed
      contents of 11 items, among which, the items of Participants, Intervention,
      Control group and Outcomes were elaborated and modified accordingly to adapt TCM
      characteristics. Since the design and reporting of trials on Chinese proprietary
      medicine and herbal decoctions are different in some aspects, the checklist
      provided two sets of elaborated item 4 (interventions). We hope that authors,
      journal editors and peer reviewers find this checklist instructive.

PMID- 18334140
TI  - [Analysis of international application of complementary and alternative
      medicine].
AB  - Traditional Chinese medicine (TCM) is an important part of complementary and
      alternative medicine (CAM) in the world medical market. The basis of
      globalization of TCM was to make sure the current situation of CAM and the role
      that TCM plays. It will improve the application and reputation of TCM by
      analyzing the global usage rate, sort of diseases, social-demographic
      characteristics of users and medical economics of CAM.

PMID- 18334141
TI  - [A new opinion on detection methods for pulse shape and pulse force].
AB  - Pulse shape and pulse force are difficult to detect in pulse taking study. But
      the application of visualized technology extends the space acquisition of pulse
      taking information, and it is possible to realize the objective detection of
      pulse shape and pulse force. Rational research thoughts and strategies could be
      informed by combining image information and other data, and it is a necessary
      method in implementing the objective detection of pulse.

PMID- 18334142
TI  - [About "Xiang" in traditional Chinese medicine].
AB  - The "Xiang" in traditional Chinese medicine (TCM) contains various meanings such
      as phenomena, image and symbols. When we consider it as a thinking mode, "Xiang"
      permeates into all TCM aspects from natural phenomena, anatomical structures of
      human tissues to physiological functions as well as pathological manifestations
      of zang-fu organs. In addition, it may have profound but different connotations.
      The authors of this article analyzed the "Xiang" in TCM according to the "Xiang"
      of nature, "Xiang" of zang-organs, "Xiang" of spirit, "Xiang" of pulse (pulse
      conditions) and "Xiang" of tongue (tongue conditions).

PMID- 18334143
TI  - [Efficacy of hirudin in treating immunoglobulin A nephropathy with hematuria: a
      randomized controlled trial].
AB  - OBJECTIVE: To investigate the curative effects and side effects of hirudin in
      treating immunoglobulin A nephropathy (IgAN) with hematuria and minimal
      proteinuria in a short-term. METHODS: Two hundred and sixty-two histologically
      confirmed cases of IgAN with hematuria and minimal proteinuria from 1998 to 2007
      were randomly divided into hirudin-treated group (peroral administration of
      Maixuekang capsules) and dipyridamole-treated group (peroral administration of
      dipyridamole). In the two groups, contrast analysis of conformation and counts of
      erythrocytes in urine, urine protein quantitation in 24 hours, levels of serum
      creatinine (Scr) and creatinine clearance rate (Ccr), blood lipid, five items of
      blood clotting and side effects was performed. RESULTS: After six-month
      treatment, the anisotrophy rate and the counts of erythrocytes in urine, and the
      urine protein quantitation in 24 hours in hirudin-treated group were decreased
      distinctly as compared with pre-treatment (P<0.01) and dipyridamole-treated group
      (P<0.05). On the other hand, Ccr was increased obviously in hirudin-treated group
      as compared with pre-treatment and dipyridamole-treated group (P<0.01). The blood
      lipid was also ameliorated in hirudin-treated group, but there was no significant
      difference. The anticoagulation effect of hirudin was better than dipyridamole
      (P<0.01). Efficacy assessment showed that the total response rate, complete
      remission rate and predominance remission rate in hirudin-treated group were
      higher than those in dipyridamole-treated group. Few side effects were found in
      both groups, and the rate of adverse reaction in gastrointestinal tract was lower
      in hirudin-treated group as compared with that in dipyridamole-treated group
      (P<0.05). CONCLUSION: Compared with dipyridamole, hirudin has superiority in
      kidney protection and decreasing the anisotrophy rate, counts of erythrocytes in
      urine and the urine protein.

PMID- 18334144
TI  - [Efficacy and safety of Deanxit combined with Wuling Capsule in treating post
      stroke depression: a randomized controlled trial].
AB  - OBJECTIVE: To evaluate the safety and efficacy of Wuling Capsule combined with
      Deanxit in treating post-stroke depression (PSD). METHODS: One hundred and
      fourteen patients with PSD were randomly divided into Wuling Capsule-treated
      group (n=39), Deanxit-treated group (n=37) and Wuling Capsule plus Deanxit
      treated group (n=38). Patients in Wuling Capsule-treated group were administered
      with three Wuling Capsules three times a day, and patients in Deanxit-treated
      group were administered with Deanxit 10.5 mg twice daily, while patients in the
      Wuling Capsule plus Deanxit-treated group were administered with both Wuling
      Capsule and Deanxit. Patients in the three groups were all treated for six weeks.
      Treatment efficacy was evaluated with Hamilton Depression Scale (HAMD) and the
      side effects were evaluated with Treatment Emergent Symptom Scale (TESS) before
      treatment and after 2-, 4-, and 6-week treatment. The blood and urine routine
      examinations were performed, and the hepatorenal functions and electrocardiogram
      were examined as well. RESULTS: There was no statistical difference in the total
      efficacy rate between Wuling Capsule-treated group and Deanxit-treated group
      (64.1% vs 64.9%, P>0.05), but the total efficacy rate of Wuling Capsule plus
      Deanxit-treated group was higher than that of the monotherapy (89.5% vs 64.1%,
      89.5% vs 64.9%, P<0.05). There were no significant side effects in Wuling Capsule
      treated group, while the incidence of side effects was 9% in both groups
      administered with Deanxit. CONCLUSION: The efficacy of Wuling Capsule plus
      Deanxit is better than that of the monotherapy in treating PSD.

PMID- 18334145
TI  - [Clinical study of Yihuo Qingxia method in treating hyperlipoidemia-related
      severe acute pancreatitis in early stage].
AB  - OBJECTIVE: To investigate the therapeutic effect of Yihuo Qingxia method, a
      traditional Chinese medicine therapeutic method for replenishing qi to activate
      blood, clearing away heat and dredging intestines, in treating hyperlipoidemia
      related severe acute pancreatitis (SAP) in early stage. METHODS: One hundred and
      four patients with hyperlipoidemia-related SAP were divided into two groups:
      early group (admitted to hospital within 3 days after onset) and late group
      (admitted to hospital from 3 days to 7 days after onset). There were 52 cases in
      each group. All the patients were treated by Yihuo Qingxia method. RESULTS: There
      were no statistical differences in 48-hour Ranson scores, CT scores, 24-hour
      acute physiology and chronic heath evaluation II scores (APACHE II scores), and
      the levels of 24-hour serum triglyceride (TG) and serum glucose in the two groups
      (P>0.05). At the 10th day after onset, the serum TG level in early group was
      lower than that in late group (P<0.01). The incidences of acute respiratory
      distress syndrome, acute renal failure, hepatic inadequacy, congestive heart
      failure, shock, encephalopathy, infection and alimentary tract hemorrhage in
      early group were higher than those in late group (P<0.05). The mortality in early
      group was lower than that in the late group (P<0.05). The length of hospital stay
      in early group was shorter than that in late group (P<0.05). CONCLUSION: Yihuo
      Qingxia method has a good efficacy in treating hyperlipoidemia-related SAP in
      early stage.

PMID- 18334146
TI  - [Diagnostic value of assay of brain natriuretic peptide in patients with sepsis
      of blood-stasis syndrome].
AB  - OBJECTIVE: To explore the diagnostic value of brain natriuretic peptide (BNP)
      level in patients with sepsis of blood-stasis syndrome. METHODS: The prospective
      method of clinical diagnostic test and evaluation principles of diagnostic test
      were applied. One hundred and seventy-four patients with sepsis were divided into
      two groups: blood-stasis syndrome group and non blood-stasis syndrome group. The
      levels of serum BNP in two groups were detected. RESULTS: The level of BNP in
      sepsis patients was related to blood-stasis syndrome (P<0.01). BNP cut-off level
      was 150 ng/L, sensitivity was 85.3%, specificity was 81%, the maximum value of
      Youden index was 0.663, and the area under the receiver operating characteristic
      curve (ROC) value was (0.886+/-0.025). CONCLUSION: BNP can be used as an
      objective index of blood-stasis syndrome diagnosis for sepsis, and BNP with
      boundary value of 150 ng/L is an optimal biological index.

PMID- 18334147
TI  - [Effects of resveratrol on matrix metalloproteinase-9 expression in hepatoma
      cells].
AB  - OBJECTIVE: To observe the effects of resveratrol on proliferation of human
      hepatocellular carcinoma cell line SMMC-7721 cells and expression of matrix
      metalloproteinase-9 (MMP-9) in vitro. METHODS: SMMC-7721 cells were treated with
      different concentrations of resveratrol for 24, 48 and 72 h, respectively. The
      effect of resveratrol on proliferation of SMMC-7721 cells was assessed with
      methyl thiazolyl tetrazolium (MTT). The expression of MMP-9 mRNA was determined
      by reverse transcription polymerase chain reaction (RT-PCR). MMP-9 protein was
      identified by Western blot analysis. RESULTS: Resveratrol could inhibit the
      proliferation of SMMC-7721 cells with dose- and time-dependent effects. Moreover,
      both MMP-9 mRNA expression and MMP-9 protein production were markedly reduced
      after resveratrol treatment. CONCLUSION: Resveratrol can inhibit the
      proliferation of SMMC-7721 cells and down-regulate MMP-9 expression. It is
      presumed that resveratrol may suppress the invasion and metastasis of
      hepatocellular carcinoma.

PMID- 18334148
TI  - [Effects of arsenic trioxide on apoptosis and proliferation of human lung cancer
      cells under hypoxia].
AB  - OBJECTIVE: To observe the effects of different concentrations of arsenic trioxide
      (As(2)O(3)) on apoptosis and proliferation of human lung cancer cell line A549 in
      vitro under hypoxia and normoxia. METHODS: A549 cells were treated with 0, 1, 2,
      4 micromol/L As2O3 for 12, 24 and 48 h under hypoxia (5% O(2)) and normoxia (21%
      O(2)). The proliferative inhibition rate of A549 cells was measured with methyl
      thiazolyl tetrazolium assay, and the apoptotic rate of A549 cells was detected by
      Annexin V/propidium iodide (PI) double staining. RESULTS: Under normoxia and
      hypoxia, 1, 2, 4 micromol/L As(2)O(3) could significantly inhibit the
      proliferation of A549 cells and induce the apoptosis of A549 cells. The results
      depended on the drug concentration and action time. And the hypoxia couldn't
      influence the effects of As(2)O(3). CONCLUSION: As(2)O(3) can inhibit the
      proliferation and induce the apoptosis of A549 cells under hypoxia and normoxia.

PMID- 18334149
TI  - [Effects of ginsenoside and berberine on secretion of immunosuppressive cytokines
      in lung carcinoma cell line PG].
AB  - OBJECTIVE: To observe the effects of ginsenoside (Gs) and berberine (Ber), two
      kinds of active components of traditional Chinese herbal medicine, on
      transforming growth factor-beta1 (TGF-beta1) and prostaglandin E2 (PGE2) in PG
      cells. METHODS: Co-culture system of human lung carcinoma cell line PG and human
      T lymphocyte cell line Jurkat was established. PG cells were treated with Gs (100
      microg/ml) and Ber (10 mug/ml) for twenty-four hours, and then cocultured with
      Jurkat cells. After 24-hour coculture, the state of Jurkat cells was observed
      with inverted microscope. The viable count of Jurkat cells was detected by trypan
      blue staining after 6- and 24-hour coculture, and the apoptosis of Jurkat cells
      was evaluated by flow cytometry. PG cells were treated with 100, 50, 25 microg/ml
      Gs and 10, 5, 2.5 microg/ml Ber respectively, and the content of TGF-beta1 and
      PGE(2) in PG cells was detected by enzyme-linked immunosorbent assay (ELISA) and
      radioimmunoassay (RIA) method. RESULTS: After coculture with PG cells treated
      with Gs and Ber, the number of Jurkat cells was less than blank control group,
      and the apoptosis rates of Jurkat cells in Gs- and Ber-treated groups were higher
      than blank control group. Gs and Ber could promote the secretion of TGF-beta1 in
      PG cells, but could not change the level of PGE(2). CONCLUSION: Gs and Ber can
      promote the growth inhibition and apoptosis of Jurkat cells induced by PG cells,
      which may be related to the up-regulation of Gs and Ber on TGF-beta1 secretion in
      PG cells.

PMID- 18334151
TI  - [Amelioration effect of Zhenqing Capsule on peripheral neuropathy in type 1
      diabetic rats].
AB  - OBJECTIVE: To investigate the effects of Zhenqing Capsule (ZQC), a compound
      traditional Chinese herbal medicine, in treating type 1 diabetic rats with
      peripheral neuropathy. METHODS: Type 1 diabetes was induced by caudal vein
      injection of high-dose streptozotocin in 30 male Wistar rats. The thirty diabetic
      rats were randomly divided into three groups: ZQC-treated group, untreated group
      and aminoguanidine-treated group. Another group of 10 rats was taken as normal
      control. After 10-week treatment, the changes of body weight and fasting plasma
      glucose level were measured, and the serum MDA level and the changes of
      neurological electrophysiology were analyzed. The samples of sciatic nerve in
      diabetic rats were taken for morphological observation. RESULTS: The MDA level in
      type 1 diabetic rats was notably reduced in ZQC-treated group as compared with
      the untreated group (P<0.01). Compared with the untreated group, ZQC could
      improve the electrophysiology of sciatic nerve including conduction velocity
      (P<0.05), latency (P<0.01) and wave amplitude (P<0.05). The nerve myelin staining
      results showed that segmental demyelination of the nerve fibers in ZQC-treated
      group was not as serious as that in the untreated group. CONCLUSION: ZQC can
      obviously ameliorate the neurological electrophysiological function and the
      pathological changes of peripheral nerve in type 1 diabetic rats through the
      removal of free radical and resistance of lipid peroxidation.

PMID- 18334150
TI  - [Effects of Valerian on the level of 5-hydroxytryptamine, cell proliferation and
      neurons in cerebral hippocampus of rats with depression induced by chronic mild
      stress].
AB  - OBJECTIVE: To explore the effects of Valerian on the level of 5-hydroxytryptamine
      (5-HT), cell proliferation and neuron number in cerebral hippocampus of rats with
      depression induced by chronic mild stress. METHODS: Seventy rats were divided
      into 7 groups: normal control, untreated, negative control, positive control, and
      low-, medium- and high-dose Valerian-treated groups. There were 10 rats in each
      group. Except for the normal control group, depression was induced in rats by
      chronic mild stress. The depressive rats in the other six groups were
      intragastrically administered with sodium carboxymethycellulose, fluoxetine, and
      low, medium and high-dose Valerian, respectively for 3 weeks. After the
      treatment, the proliferating cells in the hippocampus were labeled by injecting
      bromodeoxyuridine (BrdU) in 7 groups. The content of 5-hydroxytryptamine (5-HT)
      in the hippocampus was detected by high-performance liquid chromatography (HPLC),
      and the number of hippocampal neurons was counted by morphometry. RESULTS:
      Compared with the normal control group, the levels of 5-HT in the hippocampus in
      the low- and medium-dose Valerian-treated groups were increased and recovered to
      normal level. After the administration of low-dose Valerian for 3 weeks, the
      number of BrdU positive cells and neurons in the hippocampus of the depressive
      rats were recovered to the normal status. CONCLUSION: Minidose Valerian may
      promote the level of 5-HT and cell proliferation in the hippocampus of the
      depressive rats, and may play a role in saving injured neurons of the
      hippocampus.

PMID- 18334152
TI  - [Preventive and therapeutic effects of Bushen Huoxue Recipe on autoimmune
      premature ovarian failure in mice].
AB  - OBJECTIVE: To investigate the preventive effect of Bushen Huoxue Recipe (BSHXR),
      a compound traditional Chinese herbal medicine, on autoimmune premature ovarian
      failure (POF) in mice. METHODS: Ovarian antigen was prepared with the ovarian
      tissue of female BALB/c mice. A mouse model of POF was established by
      immunization injection of the ovarian antigen of isotype female mice on multiple
      subcutaneous sites and two posterior soles. The POF mice were treated with BSHXR
      after the first and third immunization. The levels of follicle-stimulating
      hormone (FSH), luteinizing hormone (LH) and estradiol (E2) in peripheral blood
      were detected by enzyme linked immunosorbent assay. RESULTS: Lymphocyte
      infiltration was appeared in ovarian stroma of POF mice. The levels of FSH and LH
      were evaluated and the E(2) level was decreased significantly (P<0.05). BSHXR
      could reduce the increased levels of FSH and LH, increase the level of E(2) and
      the number of growing and mature follicles. The efficacy of early treatment was
      better than that of late treatment. CONCLUSION: BSHXR can recover ovarian
      function in POF mice mainly by regulating the indiscriminate hormone level, and
      BSHXR has preventive effect on autoimmune POF in mice.

PMID- 18334153
TI  - [Experimental study of Gukangling Decoction combined with technetium [99Tc]
      methylene diphosphonate injection in treating osteoporotic rabbits].
AB  - OBJECTIVE: To evaluate the advantage of Gukangling Decoction (GKLD), a compound
      traditional Chinese herbal medicine, combined with technetium [(99)Tc] methylene
      diphosphonate injection ((99)Tc-MDP) in treating osteoporosis in rabbits.
      METHODS: A rabbit model of osteoporosis was established by intramuscular
      injection of dexamethasone (DX). Fifty-six rabbits were divided into 8 groups:
      Group A, B, C, D, E, F, G and H. Rabbits in groups A and B were intramuscularly
      injected normal saline as normal control, groups C and D were untreated groups,
      rabbits in group E were treated by (99)-MDP, rabbits in group F were treated by
      aminodiphosphate, rabbits in group G were treated by GKLD, and rabbits in group H
      were treated by (99)-MDP and GKLD. Rabbits in groups A and C were executed to
      demonstrate the establishment of the rabbit model of osteoporosis at the 8th week
      of experiment. Rabbits in the other six groups were executed after 16-week
      experiment (8-week treatment), and then bone structure and cell shape were
      observed by electron microscope, X-ray, CT and emission computed tomography
      (ECT). Bone density, biomechanical parameters, the levels of bone specific
      alkaline phosphatase (BALP) and bone Gla protein (BGP) were measured too.
      RESULTS: After 8-week of intramuscular injection of DX, the bone trabecula in
      group A were regular and showed normal configuration, while the bone trabecula in
      group C were sparse, ruptured and showed damaged form. The bone density and
      biomechanical parameters in group A were higher than those in group C, indicating
      that the rabbit model of osteoporosis was established successfully. At the 9th
      week of experiment, the results of cell pathology in group D showed that the bone
      trabeculas were sparse, ruptured, defected or had hollow section, but the bone
      trabeculas in group B were regular and dense. The bone trabeculas in groups H and
      E were restored, and were thicker than those in group D. The bone quality in
      groups H and E was better than group D significantly, the bone quality in group F
      was better than group G, and the bone quality in group G was better than group D
      slightly. CONCLUSION: GKLD combined with (99)-MDP had superiority in treating
      osteoporosis of rabbits as compared with the respective single therapy.

PMID- 18334154
TI  - [Application of quality of life scale in evaluating the efficacy of gastric
      cancer treatment].

PMID- 18334155
TI  - [Development of research on the application of traditional Chinese herbal drugs
      in root canal disinfection].

PMID- 18334156
TI  - [How to use one-way analysis of variance correctly].

PMID- 18334157
TI  - [Discussion on English translation of commonly used sentences in traditional
      Chinese medicine: part three].

PMID- 18334158
TI  - [Report of the 10th Annual Meeting of the Chinese society of Clinical Oncology].
AB  - The 10th Annual Meeting of the Chinese Society of Clinical Oncology (CSCO) was
      held on 19-23 September 2007 in Harbin. The theme of this conference was "putting
      standard multidisciplinary cancer management into practice" and special reports
      of standard multidisciplinary management on various cancers were presented. Over
      3 500 clinical oncologists and scientists participated in the 2007 CSCO Annual
      Meeting where more than ten international top experts were invited to exchange
      valuable experiences with the delegates. The programs consisted of Education
      Session, Satellite Symposium and Meet the Professor Session. The latest research
      results were presented as oral presentations and posters at the congress. Several
      hotspots were particularly highlighted in this report, including innovative
      radiotherapy and chemotherapy methods, researches on molecular targets and
      clinical trials of targeted therapy, such as endostatin, volociximab, cetuximab,
      bevacizumab and temozolomide. The remarkable research results of anti-cancer
      Chinese medicine, cancer screening and prognosis were also introduced. This
      article tries to call the attention to some hot topics in the program that are
      both new and noteworthy, and it may serve as a highlight of this important
      international cancer research meeting for clinical oncologists and scientists.

PMID- 18334159
TI  - [Twenty years later...].

PMID- 18334160
TI  - [An anion transporter is essential for spermatozoa motility].

PMID- 18334161
TI  - [Hormone therapy and risk of venous thromboembolism: new insights from the ESTHER
      study].

PMID- 18334162
TI  - [Deleterious role of CD16 in sepsis].

PMID- 18334163
TI  - [A cigarette, an aromatic...and a cancer].

PMID- 18334164
TI  - [From mollusk to man: YKL-40, a novel mediator of severe asthma].

PMID- 18334165
TI  - [One, two, three...a thousand genomes?].

PMID- 18334166
TI  - [The "Snail" genes and renal diseases: what we learn from organogenesis].

PMID- 18334167
TI  - [What is new in the genetics of type 2 diabetes].

PMID- 18334168
TI  - [STAT3 mutation identified in patients with Hyper-IgE syndrome].

PMID- 18334169
TI  - [nAG, a molecular clue for nerve dependence of regeneration].

PMID- 18334170
TI  - [Entosis, a cell death process related to cell cannibalism between tumor cells].

PMID- 18334171
TI  - [Cellular origin of Ewing's tumor. A corner of the veil is lifted].

PMID- 18334174
TI  - [Ascidian embryos: from the birth of experimental embryology to the analysis of
      gene regulatory networks].
AB  - Ascidian embryos were the first animal embryos to be experimentally manipulated
      by Man at the end of the 19th century. The mosaic theory of development was born
      from these experiments and those carried out by Conklin 20 years later. These
      astonishing animals, some of which are eaten as delicacies in France and other
      countries, belong to the tunicates, which are the only animals to produce
      cellulose. They are, however, the closest living relatives to the vertebrates.
      Neglected throughout most of the 20th century, ascidians have recently come back
      in the limelight in the wake of the sequencing of the genomes of Ciona
      intestinalis and Ciona savignyi. These small, unduplicated genomes harbour 16,000
      to 20,000 genes and are 20 times smaller than the human genome. Ciona eggs can be
      microinjected and easily electroporated, which make this system suitable for the
      study of developmental gene regulatory networks.

PMID- 18334175
TI  - [Synchronization and genetic redundancy in circadian clocks].
AB  - A network of feedback loops constitutes the basis for circadian timing in
      mammals. Complex transcriptional, post-transcriptional and post-translational
      events are also involved in the ticking of circadian clocks, allowing them to run
      autonomously with their characteristic, near-24h period. Central to the molecular
      mechanism is the CLOCK/BMAL1 heterodimer of transcription factors. Recent data
      using Clock knock-out mice however suggest that CLOCK may not be as mandatory as
      initially suggested from data gathered in the Clock mutant mouse model. Indeed,
      it appears that the Clock homolog Npas2 is able to functionally compensate for
      Clock genetic ablation. Furthermore, real-time imaging techniques using different
      clock genes knock-out lines established on a PER2 ::Luc knock-in background now
      demonstrate that persistent rhythmicity in the suprachiasmatic nuclei likely
      arises as a consequence of combined genetic redundancy and strong intercellular
      coupling, the latter characteristic being likely weakened in peripheral tissues
      such as liver or lung. The present review aims at summarizing current knowledge
      of the molecular basis of circadian clocks and possible differences between
      central and peripheral clocks in light of recent findings in Clock knock-out
      mice.

PMID- 18334176
TI  - [The molecular bases for copper uptake and distribution: lessons from yeast].
AB  - Copper exists in two oxidation states, cuprous (Cu1+) and cupric (Cu2+), which,
      respectively, can donate or accept electrons. The fact that copper has two
      readily interconvertible redox states makes it a catalytic co-factor for many
      important enzymes. Over the past years, work in a number of laboratories has
      clearly demonstrated that studies in yeast have served as a springboard for
      identifying cellular components and processes involved in copper uptake and
      distribution. In several cases, it has been shown that mammalian proteins are
      capable of functionally replacing yeast proteins, thereby revealing their
      remarkable functional conservation. For high-affinity copper transport into
      cells, it has been shown that copper transporters of the Ctr family are required.
      Upon entering the cell, copper is partitioned to different proteins and into
      different compartments within the cell. Given the potential toxicity of copper,
      specialized proteins bind copper after it enters the cell and subsequently donate
      the bound copper to their corresponding recipient proteins. Three copper-binding
      proteins, Ccs1, Cox17, and Atx1, have been identified that serve as "copper
      chaperones" to deliver copper. double dagger.

PMID- 18334177
TI  - [Granulopoeisis and leukemogenesis: lessons from congenital neutropenia].
AB  - Congenital neutropenia are extremely rare diseases, defined by a permanent or
      cyclic decrease of blood neutrophils. Molecular basis of several congenital
      neutropenia has been recently determined, involving gene coding for the
      neutrophil elastase gene (ELA2), GFI1, WAS protein and mitochondrial HAX1
      protein. These mutations, dominant (ELA2, GFI1), X-linked (WAS) and autosomal
      recessive (HAX1), result in instability of the contents of the granules-
      particularly the neutrophil elastase- or in abnormalities of the cytoskeleton,
      and possibly, in an increased apoptosis. ELA2 mutations resulting both in
      profound and permanent neutropenia, and in cyclic--pseudo sinusoidal--neutropenia
      lead to consider that time pattern is very close in the two apparently distinct
      phenotypes. This observation suggests that temporal variations of neutrophils
      could be represented by non linear functions. Congenital neutropenia,
      specifically ELA2 mutated, are also characterized by a high rate of leukemia
      (about 15% at 20 years of age). Leukemia risk does not appear to be related to an
      oncogenic effect of ELA2 mutations, but much likely to the deepness of the
      neutropenia, and the intensity of G-CSF therapy.

PMID- 18334178
TI  - [Aberrant regulation of mRNA 3' untranslated region in cancers and inflammation].
AB  - Almost 10% of mammalian coding mRNAs contain in their 3' untranslated region a
      sequence rich in adenine and uridine residues known as AU-rich element (ARE).
      Many of them encode oncogenes (for instance c-Myc and c-Fos), cell cycle
      regulators (cyclin D1, A1, B1), cytokines (TNFalpha, IL2) and growth factors (GM
      CSF) which are overexpressed in cancer or inflammatory diseases due to increased
      mRNA stability and/or translation. AREs are recognized by a group of proteins,
      collectively called AUBPs which display various functions. For instance, HuR/ELAV
      is mainly known to protect ARE-containing mRNAs from degradation, while AUF1, TTP
      and KSRP act to destabilize their bound target mRNAs and TIA/TIAR to inhibit
      their translation. Alterations in ARE sequences or AUBP abundance, cellular
      localization or activity due to post-translational modifications such as
      phosphorylation can promote or enhance malignancy or perturb immune homeostasis.
      Here, c-myc and TNFalpha are chosen as examples to illustrate how altered 3' UTR
      gene regulation impacts on pathologies.

PMID- 18334179
TI  - [AMPK: a link between metabolism and reproduction?].
AB  - 5'AMP-activated protein kinase (AMPK) is a serine/threonine kinase that acts as a
      fuel gauge in regulating energy metabolism. It restores cellular ATP levels by
      switching on catabolic pathways and switching off anabolic pathways. Some
      evidence indicates that AMPK could be also implicated in reproductive functions
      such as granulosa cell steroidogenesis and nuclear oocyte maturation in several
      species. Some metabolic hormones such as leptin, resistin, adiponectin (three
      adipokines) and ghrelin may in part act through the AMPK signaling. These
      hormones are also involved in the control of the reproductive functions at the
      hypothalamus-pituitary-gonadal axis level in both male and female. Thus, AMPK
      could be one of the signaling pathways controlling the interactions between
      energy balance and reproduction. The reproductive system is tightly coupled with
      energy balance, and thereby metabolic abnormalities can lead to the development
      of some physiopathological situations such as the polycystic ovary syndrome
      (PCOS). Women with PCOS show altered fertility mostly associated with metabolic
      disorders such as insulin-resistance, hyperinsulinemia and/or dyslipidemia.
      Metformin, an insulin-sensitizer, is used for the treatment of women with PCOS.
      It restores subnormal fertility and energy balance. Recent studies show that AMPK
      is involved in the mechanism of action of metformin. Thus, it may be a
      therapeutic target. However, further investigations are necessary to elucidate
      the functions of AMPK in both metabolic and reproductive tissues.

PMID- 18334180
TI  - [[Inflammation and drug metabolism: NF-kappB and the CAR and PXR xeno-receptors].
AB  - Decreased drug metabolism, hyperbilirubinemia and intrahepatic cholestasis are
      frequently observed during inflammation. Additionally, it has long been
      appreciated that exposure to drug metabolism-inducing xenobiotics can impair
      immune function. The nuclear receptor CAR (constitutive androstane receptor or
      NR1I3) and PXR (pregnane X receptor, NR1I2) control phase I (cytochrome P450 2B
      and 3A), phase II (GSTA, UGT1A1), and transporter (MDR1, SLC21A6, MRP2) genes
      involved in drugs metabolism, bile acids and bilirubin clearance in response to
      xenobiotics. It is well known that inflammation, through the activation of NF
      kappaB pathway, leads to a decrease of CAR, PXR and RXRalpha expression and the
      expression of their target genes. In addition, a new study reveals the mutual
      repression between PXR and NF-kappaB signaling pathways, providing a molecular
      mechanism linking xenobiotic metabolism and inflammation.

PMID- 18334181
TI  - [Kinoids: a novel generation of specific immune therapy against cytokines].
AB  - The abnormal cytokine release in the stromal microenvironment of pathologic
      tissues, contributes to the pathogenesis of viral infections such as AIDS, cancer
      and auto-immune diseases. Neovacs developed therapeutic vaccines, named Kinoids,
      which induce anti-cytokine Antibodies. Kinoids are non toxic but immunogenic
      cytokine derivatives. Kinoid immunizations induce high titre of neutralizing Abs
      to the corresponding cytokine, is well tolerated and experimentally effective. In
      transgenic mice expressing huTNFalpha, the TNFalpha kinoid decreases clinical
      signs of Rheumatoid Arthritis and in mice challenged with syngenic CT26 tumor
      cell line huVEGF kinoid inhibits lung metastases. After validation by clinical
      trials, kinoid vaccines could represent a second generation of specific immune
      therapy to be used to combat ectopic cytokines.

PMID- 18334182
TI  - [Update on avian influenza. December 2007].

PMID- 18334183
TI  - [The statistical challenge of false positives with microarrays].

PMID- 18334184
TI  - [Ayurvedic medicine and Chinese traditional medicine: first molecular bases].

PMID- 18334185
TI  - [History of the origin of Huriet-Serusclat's law (December, 1988): protection of
      patients undergoing biomedical research].

PMID- 18334186
TI  - [Heaven only knows?].

PMID- 18334187
TI  - Women in science--passion and prejudice.

PMID- 18334188
TI  - Audience effects.

PMID- 18334189
TI  - Retinoic acid.

PMID- 18334190
TI  - The origins of behavioral genetics.
AB  - The passing of Seymour Benzer has inspired various retrospectives on his
      scientific career, and much attention has been paid to his inauguration of single
      gene mutant studies of behavior in the fruitfly Drosophila melanogaster. Studies
      of genes and behavior actually go back to the beginnings of genetics. The end of
      the era marked by Benzer's life offers a good opportunity to look back at the
      origins of the field he influenced so profoundly.

PMID- 18334191
TI  - The Price equation.

PMID- 18334192
TI  - Meaningful call combinations in a non-human primate.

PMID- 18334193
TI  - Sleep: dozy worms and sleepy flies.
AB  - Recent work on quiescent states in Caenorhabditis elegans suggests that worms
      exhibit behaviours reminiscent of satiety and sleep in mammals. At a molecular
      level, signalling through the EGF receptor and protein kinase G promotes
      quiescent states in both worms and flies, suggesting conserved mechanisms for
      sleep-like behaviours.

PMID- 18334194
TI  - Social evolution: reincarnation, free-riding and inexplicable modes of
      reproduction.
AB  - We like to believe that human societies are the most complex in the animal
      kingdom, with intricate family structures and a unique repertoire of
      sophisticated social interactions. A new study reveals an insect society so
      complex that we are forced to reconsider our role as conquerors of complexity.

PMID- 18334195
TI  - Evolutionary biology: genomic clues to original sex in fungi.
AB  - Sexual identity in fungi is conferred by a diverse group of transcription
      factors. Analysis of a Zygomycota genome, representing a basal branch within the
      fungi, indicates that HMG-domain proteins were present as ancestral sex
      determinants and suggests a mechanism for the evolution of eukaryotic sex
      chromosomes.

PMID- 18334196
TI  - Sexual behaviour: a receptor for sex control in Drosophila females.
AB  - Male Drosophila manipulate the sexual behaviour of their female mating partners
      by release of a Sex-peptide, but how does this work? A G-protein-coupled receptor
      has now been identified which acts in the female flies to detect male Sex-peptide
      and trigger increased egg laying and reduced sexual receptivity.

PMID- 18334197
TI  - Plasmid segregation: is a total understanding within reach?
AB  - Recent in vitro and in vivo studies of the proteins responsible for the active
      partitioning of bacterial plasmids suggest that it will be possible to develop a
      quantitative, molecular understanding of this form of DNA segregation.

PMID- 18334198
TI  - Animal navigation: the longitude problem.
AB  - Determining longitude is incredibly difficult--for humans. Are animals fooling us
      into thinking that they have bicoordinate maps? New experiments show that at
      least some creatures effortlessly solve the seemingly insoluble problem of
      longitude.

PMID- 18334199
TI  - Developmental psychology: a precursor of moral judgment in human infants?
AB  - Human infants evaluate social interactions well before they can speak, and show a
      preference for characters that help others over characters that are not
      cooperative or are hindering.

PMID- 18334200
TI  - Plant immunity: AvrPto targets the frontline.
AB  - Bacterial pathogens must suppress host defences to cause disease. New research
      shows that the Pseudomonas effector protein AvrPto does so by directly targeting
      plant transmembrane receptor kinases involved in bacterial perception.

PMID- 18334201
TI  - Trans-synaptic plasticity: presynaptic initiation, postsynaptic memory.
AB  - A novel mechanism of persistent facilitation induced by serotonin at Aplysia
      synapses depends upon rapid postsynaptic protein synthesis and increased
      responsiveness to glutamate; whereas the memory for this synaptic change is
      postsynaptic, the initiating signal may be an increase in spontaneous release of
      glutamate from the presynaptic terminals.

PMID- 18334202
TI  - High genetic variance in life-history strategies within invasive populations by
      way of multiple introductions.
AB  - Biological invasions represent major threats to biodiversity as well as large
      scale evolutionary experiments. Invasive populations have provided some of the
      best known examples of contemporary evolution [3-6], challenging the classical
      view that invasive species are genetically depauperate because of founder
      effects. Yet the origin of trait genetic variance in invasive populations largely
      remains a mystery, precluding a clear understanding of how evolution proceeds. In
      particular, despite the emerging molecular evidence that multiple introductions
      commonly occur in the same place, their contribution to the evolutionary
      potential of invasives remains unclear. Here, by using a long-term field survey,
      mtDNA sequences, and a large-scale quantitative genetic experiment on freshwater
      snails, we document how a spectacular adaptive potential for key ecological
      traits can be accumulated in invasive populations. We provide the first direct
      evidence that multiple introductions are primarily responsible for such an
      accumulation and that sexual reproduction amplifies this effect by generating
      novel trait combinations. Thus bioinvasions, destructive as they may be, are not
      synonyms of genetic uniformity and can be hotspots of evolutionary novelty.

PMID- 18334203
TI  - In vivo monitoring of circadian timing in freely moving mice.
AB  - In mammals, the principal circadian pacemaker driving daily physiology and
      behavioral rhythms is located in the suprachiasmatic nucleus (SCN) in the
      anterior hypothalamus. The neural output of SCN is essential for the circadian
      regulation of behavioral activity. Although remarkable progress has been made in
      revealing the molecular basis of circadian rhythm generation within the SCN, the
      output pathways by which the SCN exert control over circadian rhythms are not
      well understood. Most SCN efferents target the subparaventricular zone (SPZ),
      which resides just dorsal to the SCN. This output pathway has been proposed as a
      major component involved in the outflow for circadian regulation. We have
      examined the downstream pathway of the central clock by means of multiunit neural
      activity (MUA) in freely moving mice. SCN neural activity is tightly coupled to
      environmental photic input and anticorrelated with MUA rhythm in the SPZ. In
      Clock mutant mice exhibiting attenuated circadian locomotor rhythmicity, MUA
      rhythmicity in the SCN and SPZ is similarly blunted. These results suggest that
      the SPZ plays a functional role in relaying circadian and photic signals to
      centers involved in generating behavioral activity.

PMID- 18334204
TI  - Activity versus peroxisomal targeting of PerCR.

PMID- 18334205
TI  - A trigger squeezed.

PMID- 18334206
TI  - DNA-PKcs at 7 angstrom: insights for DNA repair.

PMID- 18334207
TI  - Terminal regions of beta-catenin come into view.

PMID- 18334208
TI  - Deubiquitination of Lys63-linkage by a CYLD UBP.

PMID- 18334210
TI  - Microscale fluorescent thermal stability assay for membrane proteins.
AB  - Systematic efforts to understand membrane protein stability under a variety of
      different solution conditions are not widely available for membrane proteins,
      mainly due to technical problems stemming from the presence of detergents
      necessary to keep the proteins in the solubilized state and the background that
      such detergents usually generate during biophysical characterization. In this
      report, we introduce an efficient microscale fluorescent stability screen using
      the thiol-specific fluorochrome N-[4-(7-diethylamino-4-methyl-3
      coumarinyl)phenyl]maleimide (CPM) for stability profiling of membrane proteins
      under different solution and ligand conditions. The screen uses the chemical
      reactivity of the native cysteines embedded in the protein interior as a sensor
      for the overall integrity of the folded state. The thermal information gained by
      thorough investigation of the protein stability landscape can be effectively used
      to guide purification and biophysical characterization efforts including
      crystallization. To evaluate the method, three different protein families were
      analyzed, including the Apelin G protein-coupled receptor (APJ).

PMID- 18334209
TI  - Mammalian DNA methyltransferases: a structural perspective.
AB  - The methylation of mammalian DNA, primarily at CpG dinucleotides, has long been
      recognized to play a major role in controlling gene expression, among other
      functions. Given their importance, it is surprising how many basic questions
      remain to be answered about the proteins responsible for this methylation and for
      coordination with the parallel chromatin-marking system that operates at the
      level of histone modification. This article reviews recent studies on, and
      discusses the resulting biochemical and structural insights into, the DNA
      nucleotide methyltransferase (Dnmt) proteins 1, 3a, 3a2, 3b, and 3L.

PMID- 18334211
TI  - Crystal structure of an intact type II DNA topoisomerase: insights into DNA
      transfer mechanisms.
AB  - DNA topoisomerases resolve DNA topological problems created during transcription,
      replication, and recombination. These ubiquitous enzymes are essential for cell
      viability and are highly potent targets for the development of antibacterial and
      antitumoral drugs. Type II enzymes catalyze the transfer of a DNA duplex through
      another one in an ATP-dependent mechanism. Because of its small size and
      sensitivity to antitumoral drugs, the archaeal DNA topoisomerase VI, a type II
      enzyme, is an excellent model for gaining further understanding of the
      organization and mechanism of these enzymes. We present the crystal structure of
      intact DNA topoisomerase VI bound to radicicol, an inhibitor of human topo II,
      and compare it to the conformation of the apo-protein as determined by small
      angle X-ray scattering in solution. This structure, combined with a wealth of
      experimental data gathered on these enzymes, allows us to propose a structural
      model for the two-gate DNA transfer mechanism.

PMID- 18334213
TI  - Regulation of enzyme localization by polymerization: polymer formation by the SAM
      domain of diacylglycerol kinase delta1.
AB  - The diacylglycerol kinase (DGK) enzymes function as regulators of intracellular
      signaling by altering the levels of the second messengers, diacylglycerol and
      phosphatidic acid. The DGK delta and eta isozymes possess a common protein
      protein interaction module known as a sterile alpha-motif (SAM) domain. In DGK
      delta, SAM domain self-association inhibits the translocation of DGK delta to the
      plasma membrane. Here we show that DGK delta SAM forms a polymer and map the
      polymeric interface by a genetic selection for soluble mutants. A crystal
      structure reveals that DGKSAM forms helical polymers through a head-to-tail
      interaction similar to other SAM domain polymers. Disrupting polymerization by
      polymer interface mutations constitutively localizes DGK delta to the plasma
      membrane. Thus, polymerization of DGK delta regulates the activity of the enzyme
      by sequestering DGK delta in an inactive cellular location. Regulation by dynamic
      polymerization is an emerging theme in signal transduction.

PMID- 18334212
TI  - Colicin N binds to the periphery of its receptor and translocator, outer membrane
      protein F.
AB  - Colicins kill Escherichia coli after translocation across the outer membrane.
      Colicin N displays an unusually simple translocation pathway, using the outer
      membrane protein F (OmpF) as both receptor and translocator. Studies of this
      binary complex may therefore reveal a significant component of the translocation
      pathway. Here we show that, in 2D crystals, colicin is found outside the porin
      trimer, suggesting that translocation may occur at the protein-lipid interface.
      The major lipid of the outer leaflet interface is lipopolysaccharide (LPS). It is
      further shown that colicin N binding displaces OmpF-bound LPS. The N-terminal
      helix of the pore-forming domain, which is not required for pore formation,
      rearranges and binds to OmpF. Colicin N also binds artificial OmpF dimers,
      indicating that trimeric symmetry plays no part in the interaction. The data
      indicate that colicin is closely associated with the OmpF-lipid interface,
      providing evidence that this peripheral pathway may play a role in colicin
      transmembrane transport.

PMID- 18334214
TI  - Molecular basis for peroxisomal localization of tetrameric carbonyl reductase.
AB  - Pig heart peroxisomal carbonyl reductase (PerCR) belongs to the short-chain
      dehydrogenase/reductase family, and its sequence comprises a C-terminal SRL
      tripeptide, which is a variant of the type 1 peroxisomal targeting signal (PTS1)
      Ser-Lys-Leu. PerCR is imported into peroxisomes of HeLa cells when the cells are
      transfected with vectors expressing the enzyme. However, PerCR does not show
      specific targeting when introduced into the cells with a protein transfection
      reagent. To understand the structural basis for peroxisomal localization of
      PerCR, we determined the crystal structure of PerCR. Our data revealed that the C
      terminal PTS1 of each subunit of PerCR was involved in intersubunit interactions
      and was buried in the interior of the tetrameric molecule. These findings
      indicate that the PTS1 receptor Pex5p in the cytosol recognizes the monomeric
      form of PerCR whose C-terminal PTS1 is exposed, and that this PerCR is targeted
      into the peroxisome, thereby forming a tetramer.

PMID- 18334215
TI  - Structural dynamics of an isolated voltage-sensor domain in a lipid bilayer.
AB  - A strong interplay between the voltage-sensor domain (VSD) and the pore domain
      (PD) underlies voltage-gated channel functions. In a few voltage-sensitive
      proteins, the VSD has been shown to function without a canonical PD, although its
      structure and oligomeric state remain unknown. Here, using EPR spectroscopy, we
      show that the isolated VSD of KvAP can remain monomeric in a reconstituted
      bilayer and retain a transmembrane conformation. We find that water-filled
      crevices extending deep into the membrane around S3, a scaffold conducive to
      transport of protons/cations, are intrinsic to the VSD. Differences in solvent
      accessibility in comparison to the full-length KvAP allowed us to define an
      interacting footprint of the PD on the VSD. This interaction is centered around
      S1 and S2 and suggests a rotation of 70 degrees -100 degrees relative to Kv1.2
      Kv2.1 chimera. Sequence-conservation patterns in Kv channels, Hv channels, and
      voltage-sensitive phosphatases reveal several near-universal features suggesting
      a common molecular architecture for all VSDs.

PMID- 18334217
TI  - Regulation of neurexin 1beta tertiary structure and ligand binding through
      alternative splicing.
AB  - Neurexins and neuroligins play an essential role in synapse function, and their
      alterations are linked to autistic spectrum disorder. Interactions between
      neurexins and neuroligins regulate inhibitory and excitatory synaptogenesis in
      vitro through a "splice-insert signaling code." In particular, neurexin 1beta
      carrying an alternative splice insert at site SS#4 interacts with neuroligin 2
      (found predominantly at inhibitory synapses) but much less so with other
      neuroligins (those carrying an insert at site B and prevalent at excitatory
      synapses). The structure of neurexin 1beta+SS#4 reveals dramatic rearrangements
      to the "hypervariable surface," the binding site for neuroligins. The splice
      insert protrudes as a long helix into space, triggers conversion of loop beta10
      beta11 into a helix rearranging the binding site for neuroligins, and rearranges
      the Ca(2+)-binding site required for ligand binding, increasing its affinity. Our
      structures reveal the mechanism by which neurexin 1beta isoforms acquire
      neuroligin splice isoform selectivity.

PMID- 18334216
TI  - Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and
      dynamics of splice insertion sequence 4.
AB  - Presynaptic neurexins (NRXs) bind to postsynaptic neuroligins (NLs) to form
      Ca(2+)-dependent complexes that bridge neural synapses. beta-NRXs bind NLs
      through their LNS domains, which contain a single site of alternative splicing
      (splice site 4) giving rise to two isoforms: +4 and Delta. We present crystal
      structures of the Delta isoforms of the LNS domains from beta-NRX1 and beta-NRX2,
      crystallized in the presence of Ca(2+) ions. The Ca(2+)-binding site is
      disordered in the beta-NRX2 structure, but the 1.7 A beta-NRX1 structure reveals
      a single Ca(2+) ion, approximately 12 A from the splice insertion site, with one
      coordinating ligand donated by a glutamic acid from an adjacent beta-NRX1
      molecule. NMR studies of beta-NRX1+4 show that the insertion sequence is
      unstructured, and remains at least partially disordered in complex with NL. These
      results raise the possibility that beta-NRX insertion sequence 4 may function in
      roles independent of neuroligin binding.

PMID- 18334218
TI  - Structure of the oligosaccharyl transferase complex at 12 A resolution.
AB  - Oligosaccharyl transferase (OT) catalyzes the transfer of a lipid-linked
      oligosaccharide to the nascent polypeptide emerging from the translocon.
      Currently, there is no structural information on the membrane-embedded OT
      complex, which consists of eight different polypeptide chains. We report a 12 A
      resolution cryo-electron microscopy structure of OT from yeast. We mapped the
      locations of four essential OT subunits through a maltose-binding protein fusion
      strategy. OT was found to have a large domain in the lumenal side of endoplasmic
      reticulum where the catalysis occurs. The lumenal domain mainly comprises the
      catalytic Stt3p, the donor substrate-recognizing Wbp1p, and the acceptor
      substrate-recognizing Ost1p. A prominent groove was observed between these
      subunits, and we propose that the nascent polypeptide from the translocon threads
      through this groove while being scanned by the Ost1p subunit for the presence of
      the glycosylation sequon.

PMID- 18334219
TI  - De novo backbone trace of GroEL from single particle electron cryomicroscopy.
AB  - In this work, we employ single-particle electron cryo-microscopy (cryo-EM) to
      reconstruct GroEL to approximately 4 A resolution with both D7 and C7 symmetry.
      Using a newly developed skeletonization algorithm and secondary structure element
      identification in combination with sequence-based secondary structure prediction,
      we demonstrate that it is possible to achieve a de novo Calpha trace directly
      from a cryo-EM reconstruction. The topology of our backbone trace is completely
      accurate, though subtle alterations illustrate significant differences from
      existing crystal structures. In the map with C7 symmetry, the seven monomers in
      each ring are identical; however, the subunits have a subtly different structure
      in each ring, particularly in the equatorial domain. These differences include an
      asymmetric salt bridge, density in the nucleotide-binding pocket of only one
      ring, and small shifts in alpha helix positions. This asymmetric conformation is
      different from previous asymmetric structures, including GroES-bound GroEL, and
      may represent a "primed state" in the chaperonin pathway.

PMID- 18334220
TI  - Mechanism of activation and inhibition of the HER4/ErbB4 kinase.
AB  - HER4/ErbB4 is a ubiquitously expressed member of the EGF/ErbB family of receptor
      tyrosine kinases that is essential for normal development of the heart, nervous
      system, and mammary gland. We report here crystal structures of the ErbB4 kinase
      domain in active and lapatinib-inhibited forms. Active ErbB4 kinase adopts an
      asymmetric dimer conformation essentially identical to that observed to be
      important for activation of the EGF receptor/ErbB1 kinase. Mutagenesis studies of
      intact ErbB4 in Ba/F3 cells confirm the importance of this asymmetric dimer for
      activation of intact ErbB4. Lapatinib binds to an inactive form of the ErbB4
      kinase in a mode equivalent to its interaction with the EGF receptor. All ErbB4
      residues contacted by lapatinib are conserved in the EGF receptor and HER2/ErbB2,
      which lapatinib also targets. These results demonstrate that key elements of
      kinase activation and inhibition are conserved among ErbB family members.

PMID- 18334221
TI  - Cryo-EM structure of the DNA-dependent protein kinase catalytic subunit at
      subnanometer resolution reveals alpha helices and insight into DNA binding.
AB  - The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) regulates the
      nonhomologous end joining pathway for repair of double-stranded DNA (dsDNA)
      breaks. Here, we present a 7A resolution structure of DNA-PKcs determined by cryo
      electron microscopy single-particle reconstruction. This structure is composed of
      density rods throughout the molecule that are indicative of alpha helices and
      reveals structural features not observed in lower resolution EM structures.
      Docking of homology models into the DNA-PKcs structure demonstrates that up to
      eight helical HEAT repeat motifs fit well within the density. Surprisingly,
      models for the kinase domain can be docked into either the crown or base of the
      molecule at this resolution, although real space refinement suggests that the
      base location is the best fit. We propose a model for the interaction of DNA with
      DNA-PKcs in which one turn of dsDNA enters the central channel and interacts with
      a resolved alpha-helical protrusion.

PMID- 18334223
TI  - A helical string of alternately connected three-helix bundles for the cell wall
      associated adhesion protein Ebh from Staphylococcus aureus.
AB  - The 1.1 MDa cell-wall-associated adhesion protein of staphylococci, Ebh, consists
      of several distinct regions, including a large central region with 52 imperfect
      repeats of 126 amino acid residues. We investigated the structure of this giant
      molecule by X-ray crystallography, circular dichroism (CD) spectrometry, and
      small-angle X-ray scattering (SAXS). The crystal structure of two repeats showed
      that each repeat consists of two distinct three-helix bundles, and two such
      repeats are connected along the long axis, resulting in a rod-like structure that
      is 120 A in length. CD and SAXS analyses of the samples with longer repeats
      suggested that each repeat has an identical structure, and that such repeats are
      connected tandemly to form a rod-like structure in solution, the length of which
      increased proportionately with the number of repeating units. On the basis of
      these results, it was proposed that Ebh is a 320 nm rod-like molecule with some
      plasticity at module junctions.

PMID- 18334222
TI  - Crystal structure of a full-length beta-catenin.
AB  - beta-catenin plays essential roles in cell adhesion and Wnt signaling, while
      deregulation of beta-catenin is associated with multiple diseases including
      cancers. Here, we report the crystal structures of full-length zebrafish beta
      catenin and a human beta-catenin fragment that contains both the armadillo repeat
      and the C-terminal domains. Our structures reveal that the N-terminal region of
      the C-terminal domain, a key component of the C-terminal transactivation domain,
      forms a long alpha helix that packs on the C-terminal end of the armadillo repeat
      domain, and thus forms part of the beta-catenin superhelical core. The existence
      of this helix redefines our view of interactions of beta-catenin with some of its
      critical partners, including ICAT and Chibby, which may form extensive
      interactions with this C-terminal domain alpha helix. Our crystallographic and
      NMR studies also suggest that the unstructured N-terminal and C-terminal tails
      interact with the ordered armadillo repeat domain in a dynamic and variable
      manner.

PMID- 18334224
TI  - A high-throughput, low-cost method for the preparation of "sequencing-ready"
      phage DNA template.
AB  - We have developed a simple and efficient protocol for the isolation of good
      quality recombinant phage DNA useful for all downstream processing, including
      automated sequencing. The overnight-grown phage particles were effectively
      precipitated (without any contaminating Escherichia coli DNA and other culture
      media components) by adjusting the pH of the culture medium to 5.2 with sodium
      acetate, followed by addition of ethanol to 25%. The phage DNA was selectively
      precipitated with ethanol in the presence of guanidinium thiocyanate under
      alkaline pH, resulting in uniform quality and quantity of phage DNA. The quality
      of the phage DNA preparation was demonstrated by DNA sequencing that provided an
      average read length of >700 bases (PHRED20 quality). This protocol for plating,
      picking, growing, and subsequent DNA purification of individual phage clones can
      be completely automated using any standard robotic platform. This protocol does
      not require any commercial kits and can be completed within 2h.

PMID- 18334225
TI  - Measurement of spermidine/spermine-N1-acetyltransferase activity by high
      performance liquid chromatography with N1-dansylnorspermine as the substrate.
AB  - We developed a nonradioactive assay to measure spermidine/spermine N(1)
      acetyltransferase (SSAT) activity by high-performance liquid chromatography
      (HPLC). N(1)-dansylnorspermine was prepared and evaluated as a substrate of
      acetylation with acetyl-CoA by SSAT in rat hepatoma (HTC) cells. Kinetic studies
      revealed that the K(m) values of N(1)-dansylnorspermine and acetyl-CoA were
      approximately 11 and 13 microM, respectively. When the assay method was applied
      to HTC cell samples, the SSAT activity, even at the control level, could easily
      be detected in as few as 20 microg protein of cell extract corresponding to 1 x
      10(5) cells per determination, and 100 samples could be analyzed overnight. Thus,
      our HPLC method is a rapid and sensitive assay for the measurement of SSAT
      activity.

PMID- 18334226
TI  - The response of bone to mechanical loading and disuse: fundamental principles and
      influences on osteoblast/osteocyte homeostasis.
AB  - Bone's response to increased or reduced loading/disuse is a feature of many
      clinical circumstances, and our daily life, as habitual activities change.
      However, there are several misconceptions regarding what constitutes loading or
      disuse and why the skeleton gains or loses bone. The main purpose of this article
      is to discuss the fundamentals of the need for bone to experience the effects of
      loading and disuse, why bone loss due to disuse occurs, and how it is the target
      of skeletal physiology which drives pathological bone loss in conditions that may
      not be seen as being primarily due to disuse. Fundamentally, if we accept that
      hypertrophy of bone in response to increased loading is a desirable occurrence,
      then disuse is not a pathological process, but simply the corollary of adaptation
      to increased loads. If adaptive processes occur to increase bone mass in response
      to increased load, then the loss of bone in disuse is the only way that
      adaptation can fully tune the skeleton to prevailing functional demands when
      loading is reduced. The mechanisms by which loading and disuse cause bone
      formation or resorption are the same, although the direction of any changes is
      different. The osteocyte and osteoblast are the key cells involved in sensing and
      communicating the need for changes in mass or architecture as a result of changes
      in experienced loading. However, as those cells are affected by numerous other
      influences, the responses of bone to loading or disuse are not simple, and alter
      under different circumstances. Understanding the principles of disuse and loading
      and the mechanisms underlying them therefore represents an important feature of
      bone physiology and the search for targets for anabolic therapies for skeletal
      pathology.

PMID- 18334227
TI  - Diterpene, 16-phyllocladanol enhances Th1 polarization induced by LPS-primed DC,
      but not TNF-alpha-primed DC.
AB  - 16-Phyllocladanol is diterpene isolated form the heartwood of Cryptomeria
      japonica. We demonstrate that the effect of 16-phyllocladanol on the phenotypic
      and functional maturation of human monocytes-derived DC in vitro. Human monocytes
      were exposed to 16-phyllocladanol alone, or in combination with LPS and
      thereafter co-cultured with naive T cells. The expression levels of CD83 and HLA
      DR on LPS-primed DC were enhanced by 16-phyllocladanol. 16-Phyllocladanol dose
      dependently augmented the T cell stimulatory capacity in an allo MLR to LPS
      primed DC and the production of IL-12p70 by LPS-primed DC. The cytokine
      production by 16-phyllocladanol-primed DC was not inhibited by anti-TLR2 and 4
      mAbs. IFN-gamma secretion from naive T cells co-cultured with DC differentiated
      with LPS was also augmented by 16-phyllocladanol. These results suggest that the
      enhancement of Th1 cells polarization to LPS-primed DC induced by 16
      phyllocladanol via the activation of IL-12p70 and independent on TLR2 or TLR4.

PMID- 18334228
TI  - Localization of plasma membrane and secretory calcium pumps in the mammary gland.
AB  - Until recently the mechanism for the enrichment of milk with calcium was thought
      to be almost entirely via the secretory pathway. However, recent studies suggest
      that a plasma membrane calcium ATPase, PMCA2, is the primary mechanism for
      calcium transport into milk, highlighting a major role for apical calcium
      transport. We compared the expression of the recently identified secretory
      calcium ATPase, SPCA2, and SPCA1, in the mouse mammary gland during development.
      SPCA2 levels increased over 35-fold during lactation with expression localized to
      luminal secretory cells, while SPCA1 increased only a modest 2-fold and was
      expressed throughout the cells of the mammary gland. We also observed major
      differences in the localization of PMCA2 and PMCA1. Our studies highlight the
      likely specific roles of PMCA2 and SPCA2 in lactation and indicate that calcium
      transport into milk is a complex interplay between apical and secretory pathways.

PMID- 18334229
TI  - Extracellular annexin A5: functions of phosphatidylserine-binding and two
      dimensional crystallization.
AB  - In normal healthy cells phosphatidylserine is located in the inner leaflet of the
      plasma membrane. However, on activated platelets, dying cells and under specific
      circumstances also on various types of viable leukocytes phosphatidylserine is
      actively externalized to the outer leaflet of the plasma membrane. Annexin A5 has
      the ability to bind in a calcium-dependent manner to phosphatidylserine and to
      form a membrane-bound two-dimensional crystal lattice. Based on these abilities
      various functions for extracellular annexin A5 on the phosphatidylserine
      expressing plasma membrane have been proposed. In this review we describe
      possible mechanisms for externalization of annexin A5 and various processes in
      which extracellular annexin A5 may play a role such as blood coagulation,
      apoptosis, phagocytosis and formation of plasma membrane-derived microparticles.
      We further highlight the recent discovery of internalization of extracellular
      annexin A5 by phosphatidylserine-expressing cells.

PMID- 18334230
TI  - Expression of phase I and phase II genes in mouse embryonic stem cells cultured
      in the presence of 2,3,7,8-tetrachlorodibenzo-para-dioxin.
AB  - Embryonic stem (ES) cells have features that resemble the pluripotent cells of
      peri-implantation embryos and have been used as an in vitro model to assess the
      effects of test substances on these stages of development. Here, for the first
      time, we report on the effects of the xenobiotic 2,3,7,8-tetrachlorodibenzo-para
      dioxin (TCDD) on mouse ES cells cultured with TCDD at concentrations ranging from
      0.0001 to 100 nM for 15 min to 48 h. TCDD effects were determined by analysing
      the induction of Cyp1A1, Cyp1A2, Cyp1B1 (phase I) and Nqo1, Gsta1, Ugt1a6 (phase
      II) genes. Cyp1A1 was the phase I gene most rapidly induced (4 h at 1 nM); Cyp1B1
      was induced at 48 h (1 nM), whereas Cyp1A2 expression was not affected. TCDD did
      not alter phase II gene expression, which remained at basal levels throughout the
      48 h of culture. We studied more accurately the expression of Cyp1A1, the
      earliest gene to respond to the presence of TCDD. We found that: 1) Cyp1A1 gene
      induction is dependent on the duration of exposure (precisely it is first induced
      after 3 h of culture at 1 nM, the minimum effective-dose); 2) Cyp1A1 induction
      requires the continuous presence of TCDD, being interrupted 4 h after removal of
      the xenobiotic; and 3) induced expression of CYP1A1 protein is dependent on TCDD
      concentration, the higher the concentration the earlier the production of the
      enzyme. Furthermore, after 48 h of treatment, TCDD did not promote either
      apoptosis or changes to the differentiation status of the ES cells. These results
      are the first important step to investigate the effects of dioxin on the very
      early stages of mammalian development.

PMID- 18334231
TI  - Chronic kidney disease in special populations.

PMID- 18334232
TI  - Clinical challenges in vulnerable CKD populations.

PMID- 18334234
TI  - Disparities in renal endowment: causes and consequences.
AB  - In humans, nephrogenesis is completed by 36 weeks of gestation. Thus, human
      kidney development is complete at the time of birth in full-term infants. Those
      infants born before 36 weeks of gestation are still undergoing nephrogenesis for
      several weeks after their preterm birth and, accordingly, may be exposed to
      medications that impact the kidney during its final stages of renal development.
      The ultimate nephron number (nephron endowment) may influence future response to
      kidney injury, should it occur. The concept that nephron number may strongly
      influence blood pressure as well as susceptibility to kidney disease in later
      life developed in parallel with that of perinatal programming, which holds that
      the perinatal milieu causes changes that permanently alter organ structure and
      function, preordaining adult physiology to some extent. Both concepts together
      may help elucidate, at least in part, the pathogenesis of not only primary but
      secondary hypertension. This article summarizes human data on nephron number and
      its evaluation and considers the circumstances, implication, and management of
      persons born with or acquiring a decreased complement of nephrons early in life.
      Insufficient data exist to predict outcome or guide management. However, a common
      sense approach of avoiding nephrotoxins and minimizing renal stress is indicated.

PMID- 18334233
TI  - Intrauterine growth restriction: fetal programming of hypertension and kidney
      disease.
AB  - The etiology of hypertension historically includes 2 components: genetics and
      lifestyle. However, recent epidemiologic studies report an inverse relationship
      between birth weight and hypertension suggesting that a suboptimal fetal
      environment may also contribute to increased disease in later life. Experimental
      studies support this observation and indicate that cardiovascular/kidney disease
      originates in response to fetal adaptations to adverse conditions during prenatal
      life.

PMID- 18334235
TI  - Geriatric hemodialysis rehabilitation care.
AB  - The 2 objectives of this review are to provide background information about
      functional status in older dialysis patients and to discuss the utility of
      geriatric dialysis rehabilitation. We performed a literature search using PubMed
      and MedLine. All relevant texts were reviewed for information on functional
      status and disability in the renal population and in the general population. Data
      pertaining to geriatric rehabilitation and geriatric dialysis rehabilitation were
      also reviewed. We show how disability and functional limitations are more
      prevalent in populations with advanced stages of chronic kidney disease (CKD)
      compared with those with only mild stages of CKD. We describe data showing that
      dedicated geriatric dialysis rehabilitation units, using interdisciplinary care
      models, result in more than 70% of patients meeting their rehabilitation goals
      and being successfully discharged home. Nephrologists increasingly will be faced
      with problems arising from functional decline. We conclude by offering
      suggestions for future changes that may help to stem the rising tide of dialysis
      disability.

PMID- 18334237
TI  - Maintaining quality of life at the end of life in the end-stage renal disease
      population.
AB  - The rapidly advancing age of incident dialysis patient has coincided with a
      rising mortality rate during the first year of dialysis. This is occurring
      despite a steady decline in mortality of prevalent patients. These statistics
      suggest that there is a subset of sick, elderly dialysis patients who will not
      survive the first 6 months of dialysis. It may be that these patients would be
      better served with a conservative, palliative approach that does not include
      initiation of dialysis. Even though hospice care is universally available to the
      Center for Medicare and Medicaid Services population, dialysis patients encounter
      many barriers to obtaining this benefit and have a hospice utilization rate only
      one quarter that of cancer patients. This article discusses the barriers to and
      goals of palliative care in the chronic kidney disease/end-stage renal disease
      population.

PMID- 18334238
TI  - Potential impact of Medicare Part D in the end-stage renal disease population.
AB  - Since 2006, end-stage renal disease (ESRD) patients enrolled in Medicare are also
      eligible to enroll in the voluntary prescription drug program, Medicare Part D,
      which is administered by private sector entities called prescription drug plans
      (PDPs) or Medicare Advantage Part D plans. Approximately 84% of ESRD patients
      should be eligible to receive Part D benefits based on Medicare coverage, but the
      percentage who lack adequate prescription coverage and are enrolled is unclear.
      Dually eligible (Medicare and Medicaid) ESRD patients were automatically enrolled
      in PDPs if they did not self-enroll. Many experienced problems after Part D
      implementation, including interruptions in prescription drug coverage, formulary
      issues, and difficulties when seeking appeals. Several key ESRD medications are
      not covered by Part D plans. Trade-name ESRD medications are often placed in
      higher formulary tiers requiring higher copayment. Enhanced plans covering more
      medications require higher premiums. ESRD patients have higher out-of-pocket
      expenses under Part D than general Medicare patients and are more likely to reach
      and go through the coverage gap and to reach catastrophic coverage. The
      complexities of Medicare Part D make problems inevitable; ESRD patients may be
      more vulnerable to these problems than the general Medicare population, but
      further data are needed.

PMID- 18334236
TI  - Cognitive impairment in the aging dialysis and chronic kidney disease
      populations: an occult burden.
AB  - The high burden of cognitive impairment in hemodialysis and chronic kidney
      disease (CKD) patients has only recently become recognized. Up to 70% of
      hemodialysis patients aged 55 years and older have moderate to severe chronic
      cognitive impairment, yet it is largely undiagnosed. Recent studies describe the
      strong graded relation between estimated glomerular filtration rate and cognitive
      function in CKD patients. The process of conventional hemodialysis may induce
      recurrent episodes of acute cerebral ischemia, which, in turn, may contribute to
      acute decline in cognitive function during dialysis. Thus, the worst time to
      communicate with dialysis patients may be during the hemodialysis session. Both
      symptomatic and occult, subclinical ischemic cerebrovascular disease appears to
      play a large role in a proposed model of accelerated vascular cognitive
      impairment in these populations. Severe cognitive impairment or dementia among
      hemodialysis patients is associated with an approximately 2-fold increased risk
      of both mortality and dialysis withdrawal. Predialysis cognitive screening and
      adding dementia to the list of comorbidities on Form 2728 would provide critical
      information regarding the benefit versus risks of receiving dialysis. It could
      also improve quality of care and outcomes by raising clinicians' awareness of the
      potential effects of cognitive impairment on medication, fluid, and dietary
      compliance and the ability to make advance directive decisions among dialysis
      patients. Although much remains to be learned regarding the pathophysiology of
      cognitive impairment in kidney disease, the public health implications of this
      substantial burden are immediate.

PMID- 18334239
TI  - Racial and ethnic differences in trends of end-stage renal disease: United
      States, 1995 to 2005.
AB  - End-stage renal disease (ESRD) disproportionately affects racial/ethnic minority
      populations in the United States, whereas the prevalence of ESRD risk factors
      such as diabetes continues to increase. Using data from the US Renal Data System,
      we examined trends in ESRD incidence, including ESRD caused by diabetes or
      hypertension. We determined the total number of persons in the United States by
      race/ethnicity who began treatment during 1995 to 2005 for ESRD and for ESRD with
      diabetes or hypertension as the primary diagnosis. Incidence rates were
      calculated by using census data and age-adjusted based on the 2000 US standard
      population. Joinpoint regression was used to analyze trends. Overall, during 1995
      to 2005, the age-adjusted ESRD incidence increased from 260.7 per million to
      350.9 per million, but the rate of increase slowed from 1998 to 2005. In the
      2000s, compared with the 1990s, the age-adjusted ESRD incidence has continued to
      increase but at a slower rate among whites and blacks and has decreased
      significantly among Native Americans, Asians, and Hispanics. The disparity gap in
      ESRD incidence between minority populations and whites narrowed during 1995 to
      2005. Continued interventions to reduce the prevalence of ESRD risk factors are
      needed to decrease ESRD incidence.

PMID- 18334240
TI  - Community-partnered approaches to enhance chronic kidney disease awareness,
      prevention, and early intervention.
AB  - There is a need to increase community involvement in addressing the growing
      burden of chronic kidney disease (CKD). Community-partnered participatory
      research (CPPR) is a collaborative approach that equitably involves academic,
      community, and professional partners in research, and the development of shared
      goals and of interventional programs to attain these goals. We present a case
      study of the processes, strategies, and activities concerning the interface of
      World Kidney Day goals and community-academic partnerships using a CPPR model
      focused on CKD. We show that CPPR methods can be used to (1) bring together
      community and academic leaders around goal sharing and research agenda
      development, (2) convene a community/professional conference aimed at knowledge
      transfer and data collection among partners, and (3) develop workgroups from a
      diverse group of participants to collaborate in community partnered strategies to
      reduce the burden of CKD. Participants included health care professionals,
      patients, faith-based professionals, government employees and officials,
      academics, caregivers, and community members. Follow-up workgroups developed
      action plans to address shared concerns. Using CPPR practices and principles, we
      were able to incorporate World Kidney Day objectives with community-derived goals
      to develop a community-partnered infrastructure, shared objectives, and
      workgroups to reduce the burden of chronic kidney disease.

PMID- 18334241
TI  - Chronic kidney disease risk reduction in a Hispanic population through pharmacist
      based disease-state management.
AB  - The purpose of this study was to evaluate the ability of a pharmacist-based
      disease-state management service to improve the care of indigent, predominately
      Spanish-speaking patients with diabetes mellitus and common comorbid conditions
      at high risk for the development of chronic kidney disease (CKD). Patients at
      high risk for developing CKD who have diabetes at a community health center were
      placed in a pharmacist-based disease state management service for CKD risk
      reduction. A residency-trained, bilingual, certified diabetes educator, with a
      PharmD served as the patient's provider using diagnostic, educational, and
      therapeutic management services under a medical staff approved collaborative
      practice agreement. Outcomes were assessed by using national standards of care
      for disease control and prevention screening. The impact on CKD was shown with a
      mean A1C decrease of 2% and improvement in the proportion of patients at target
      goals for blood pressure, A1C, and cholesterol levels and receiving aspirin and
      angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. A
      pharmacist-based disease-state management service for CKD risk reduction, care of
      diabetes, and frequently associated comorbid conditions improved compliance with
      national standards for diabetes care in a high-risk population.

PMID- 18334242
TI  - Reducing the burden of chronic kidney disease among American Indians.
AB  - American Indians (AIs) and Alaska Natives (ANs) have experienced a dramatic rise
      in type 2 diabetes and associated complications, including chronic kidney disease
      (CKD) over the past half century. At the end of 2005, the national prevalence of
      end-stage renal disease (ESRD) in AIs/ANs was 2.5 times greater than that for
      white Americans, with rates significantly higher among communities of the
      southwest United States. Evidence of CKD among AIs/ANs with diabetes includes
      abnormal protein excretion in 30% and estimated glomerular filtration rate (eGFR)
      <60 mL/min/m(2) in 17%. In order to address the growing burden of CKD, the Indian
      Health Service established the Kidney Disease Program to improve the screening of
      and the management of diabetics with CKD. Routine reporting of eGFR, yearly
      monitoring of protein excretion, utilization of renin-angiotensin system (RAS)
      antagonists, and aggressive control of blood pressure were implemented in
      association with enhanced patient and provider education. By 2006, 82% of
      hypertensive diabetics were receiving a RAS antagonist. Implementation of these
      efforts has been associated with a 31% decrease in ESRD incidence among AIs/ANs
      with diabetes. This program of improvements in CKD care implemented by a federal
      agency serving a high-risk population with limited resources may be a useful
      model for others.

PMID- 18334243
TI  - State approaches to stem toll of chronic kidney disease.
AB  - Two dozen states have undertaken initiatives to address chronic kidney disease
      (CKD), with the goal of facilitating early identification of CKD and intervention
      to prevent the progression of CKD and its comorbidities. Each state has
      approached this goal in a different fashion. The impact of these varying
      initiatives should be evaluated so as to guide policy development in other
      jurisdictions.

PMID- 18334244
TI  - Ethical issues in the care of vulnerable chronic kidney disease patients: the
      elderly, cognitively impaired, and those from different cultural backgrounds.
AB  - Numerous ethical issues such as the appropriate initiation or withdrawal of
      dialysis are inherent when one cares for patients with chronic kidney disease
      (CKD). Conflicts concerning decisions to withhold or withdraw dialysis often
      involve particularly vulnerable CKD patients such as the elderly, those with
      cognitive impairment, or those who come from different cultural backgrounds.
      Issues related to renal replacement therapy in vulnerable or special CKD
      populations will be explored within an ethical framework based on the principles
      of autonomy (self-determination), beneficence (to maximize good), nonmaleficence
      (to not cause harm), and justice (what is due or owed).

PMID- 18334245
TI  - Iron indices and vitamin D receptor polymorphisms in hemodialysis patients.
AB  - Cardiovascular disease caused by accelerated atherosclerosis is the major
      determinant of morbidity and mortality in chronic kidney disease patients.
      Vitamin D and its analogs provide survival benefit for hemodialysis (HD)
      patients. Vitamin D exerts its effects through the vitamin D receptor (VDR) that
      is coded for by a gene showing several polymorphisms that, in turn, are
      associated with a variety of diseases and differential responses to vitamin D. In
      this study, we evaluated the association between 4 VDR polymorphisms (ie, those
      identified by the restriction enzymes BsmI, ApaI, TaqI, and FokI) and iron
      indices (serum iron, transferrin, transferrin saturation, and ferritin) in 88
      hemodialysis patients routinely treated with vitamin D. The absence or presence
      of the BsmI, ApaI, TaqI, and FokI restriction sites were denominated B and b, A
      and a, T and t, F and f, respectively. Our results show that in HD patients with
      transferrin saturation <20%, the F allele was more frequent than in HD patients
      with transferrin saturation >20% (P = .03). This relationship may provide a link
      between VDR alleles and iron and nutritional markers, which are highly predictive
      variables of cardiovascular morbidity and mortality in hemodialysis patients.

PMID- 18334247
TI  - Abstracts of the International Bone and Mineral Society Davos Workshops: Bone
      Biology and Therapeutics. March 9-14, 2008. Davos, Switzerland.

PMID- 18334246
TI  - Self-efficacy and self-management behaviors in patients with chronic kidney
      disease.
AB  - Although past research has examined self-management among patients with end-stage
      renal disease (ESRD), little is known about self-management in patients with
      chronic kidney disease (CKD). In this cross-sectional survey (no intervention),
      174 patients with CKD (serum creatinine > or =1.7 mg/dL) completed self-reported
      measures of self-efficacy, physical and mental functioning, and self-management.
      The purpose of the study was to explore the association between patients'
      perceived self-efficacy and their self-management behaviors. Five types of self
      management behaviors were measured: communication with caregivers, partnership in
      care, self-care, self-advocacy, and medication adherence. Controlling for other
      relevant variables including age, education, diabetic status, hypertension, serum
      creatinine, physical functioning, and mental health functioning, higher perceived
      self-efficacy scores were associated with increased communication, partnership,
      self-care, and medication-adherence behaviors. In this study, patients' perceived
      self-efficacy was a more consistent correlate of self-management behavior than
      were demographic or health characteristics. Because self-management has been
      associated with positive patient outcomes, fostering self-management by
      supporting patient self-efficacy may have long-term benefits.

PMID- 18334249
TI  - Relationships between glycosaminoglycan and receptor binding sites in chemokines
      the CXCL12 example.
AB  - Chemokines are small proteins, promoting directional migration and activation of
      different cells through binding to specific receptors. Most chemokines also bind
      to heparan sulfate (HS), a family of complex and highly sulfated
      glycosaminoglycan (GAG) found at the cell surface and in the extracellular
      matrix. This class of molecules has recently emerged as critical regulators of
      many events involving cell response to the external environment. Binding to HS is
      thought to be functionally important. Current models suggested that HS ensures
      the correct positioning of chemokines within tissues and maintains haptotactic
      gradients of the proteins along cell surfaces, thus providing directional cues
      for migrating cells. On the chemokine surface, the GAG binding epitopes can be
      displayed on different areas, some of which overlap the receptor binding domain,
      while others are clearly separated. We review here some structural aspects of the
      interaction between GAGs or receptors and chemokines. In particular, we will
      address the case of CXCL12, a chemokine whose receptor binding site is distinct
      from the GAG binding site and whose different isoforms display different GAG
      binding abilities. This chemokine system thus offers an unprecedented opportunity
      to ascertain the importance of chemokine/GAG interaction in the regulation of
      cell migration.

PMID- 18334251
TI  - Disruption of Smad4 in neural crest cells leads to mid-gestation death with
      pharyngeal arch, craniofacial and cardiac defects.
AB  - TGFbeta/BMP signaling pathways are essential for normal development of neural
      crest cells (NCCs). Smad4 encodes the only common Smad protein in mammals, which
      is a critical nuclear mediator of TGFbeta/BMP signaling. In this work, we sought
      to investigate the roles of Smad4 for development of NCCs. To overcome the early
      embryonic lethality of Smad4 null mice, we specifically disrupted Smad4 in NCCs
      using a Cre/loxP system. The mutant mice died at mid-gestation with defects in
      facial primordia, pharyngeal arches, outflow tract and cardiac ventricles.
      Further examination revealed that mutant embryos displayed severe molecular
      defects starting from E9.5. Expression of multiple genes, including Msx1, 2, Ap-2
      alpha, Pax3, and Sox9, which play critical roles for NCC development, was
      downregulated by NCC disruption of Smad4. Moreover, increased cell death was
      observed in pharyngeal arches from E10.5. However, the cell proliferation rate in
      these areas was not substantially altered. Taken together, these findings provide
      compelling genetic evidence that Smad4-mediated activities of TGFbeta/BMP signals
      are essential for appropriate NCC development.

PMID- 18334252
TI  - The nucleosome remodeling factor (NURF) regulates genes involved in Drosophila
      innate immunity.
AB  - The Drosophila nucleosome remodeling factor (NURF) is an ISWI-containing
      chromatin remodeling complex that catalyzes ATP-dependent nucleosome sliding. By
      sliding nucleosomes, NURF has the ability to alter chromatin structure and
      regulate transcription. Previous studies have shown that mutation of Drosophila
      NURF induces melanotic tumors, implicating NURF in innate immune function. Here,
      we show that NURF mutants exhibit identical innate immune responses to gain-of
      function mutants in the Drosophila JAK/STAT pathway. Using microarrays, we
      identify a common set of target genes that are activated in both mutants. In
      silico analysis of promoter sequences of these defines a consensus regulatory
      element comprising a STAT-binding sequence overlapped by a binding-site for the
      transcriptional repressor Ken. NURF interacts physically and genetically with
      Ken. Chromatin immunoprecipitation (ChIP) localizes NURF to Ken-binding sites in
      hemocytes, suggesting that Ken recruits NURF to repress STAT responders. Loss of
      NURF leads to precocious activation of STAT target genes.

PMID- 18334250
TI  - Dendritic cells from HIV-1 infected individuals are less responsive to toll-like
      receptor (TLR) ligands.
AB  - We compared TLR responsiveness in PBMC from HIV-1-infected and uninfected
      individuals using the TLR agonists: TLR7 (3M-001), TLR8 (3M-002), and TLR7/8 (3M
      011). Activation and maturation of plasmacytoid dendritic cells (pDC) were
      measured by evaluating CD86, CD40, and CD83 expression and myeloid dendritic cell
      (mDC) activation was measured by evaluating CD40 expression. All agonists tested
      induced activation and maturation of pDC in PBMC cultures of cells from HIV+ and
      HIV- individuals. The TLR7 agonist induced significantly less pDC maturation in
      cells from HIV+ individuals. Quantitative assessment of secreted IFN-alpha and
      pro-inflammatory cytokines at the single cell level showed that pDC from HIV+
      individuals stimulated with TLR7 and TLR7/8 induced IFN-alpha. TLR8 and TLR7/8
      agonists induced IL-12 and COX-2 expression in mDC from HIV+ and HIV-
      individuals. Understanding pDC and mDC activation and maturation in HIV-1
      infection could lead to more rational development of immunotherapeutic strategies
      to stimulate the adaptive immune response to HIV-1.

PMID- 18334253
TI  - Upregulation of the let-7 microRNA with precocious development in lin-12/Notch
      hypermorphic Caenorhabditis elegans mutants.
AB  - The lin-12/Notch signaling pathway is conserved from worms to humans and is a
      master regulator of metazoan development. Here, we demonstrate that lin-12/Notch
      gain-of-function (gf) animals display precocious alae at the L4 larval stage with
      a significant increase in let-7 expression levels. Furthermore, lin-12(gf)
      animals display a precocious and higher level of let-7 gfp transgene expression
      in seam cells at L3 stage. Interestingly, lin-12(gf) mutant rescued the lethal
      phenotype of let-7 mutants similar to other known heterochronic mutants. We
      propose that lin-12/Notch signaling pathway functions in late developmental
      timing, upstream of or in parallel to the let-7 heterochronic pathway.
      Importantly, the human microRNA let-7a was also upregulated in various human cell
      lines in response to Notch 1 activation, suggesting an evolutionarily conserved
      cross-talk between let-7 and the canonical lin-12/Notch signaling pathway.

PMID- 18334254
TI  - Protective effects of ACE inhibitors on vascular endothelial dysfunction induced
      by exogenous advanced oxidation protein products in rats.
AB  - To explore detrimental effects of advanced oxidation protein products-bovine
      serum albumin (BSA) on endothelial function and compare the favorable effects of
      angiotensin-converting enzyme (ACE) inhibitors: captopril and enalapril. Male
      Sprague-Dawley rats were randomly divided into groups: control, advanced
      oxidation protein products-BSA, captopril (10, 20 mg/kg/day), enalapril (15
      mg/kg/day), and N(G)-nitro-l-arginine methyl ester (l-NAME, 300 mg/kg/day) plus
      captopril (20 mg/kg/day) groups. All animals were given advanced oxidation
      protein products-BSA (100 mg/kg/day, i.v.) except for control group (iv. equal
      volume of PBS). Rats in other groups were received different drugs
      intragastrically after advanced oxidation protein products-BSA administration.
      Endothelium-dependent relaxation of thoracic aorta was assayed. Content of
      nitrite/nitrate (NO), malondialdehyde (MDA), activities of glutathione peroxidase
      (GSH-Px), superoxide dismutase (SOD) and of ACE in Sera, as well as renal
      function index including blood urea nitrogen and creatinine were measured. After
      30 days, the endothelium-dependent relaxation of blood vessels in received
      advanced oxidation protein products-BSA rats was significantly impaired compared
      with control rats. The impairment was accompanied by decreases of serum NO,
      activity of GSH-Px and SOD. Administration of captopril and enalapril not only
      decreased damage of endothelium-dependent relaxation, but also reverse the
      changes of MDA levels, NO content and activity of SOD. The protective effect of
      captopril was abolished by L-NAME. Blood urea nitrogen and creatinine had no
      significant differences between various groups. ACE activities were decreased in
      high captopril and enalapril groups, but did not significantly change in other
      groups. The results suggested that captopril and enalapril have similar effects
      on endothelial dysfunction induced by advanced oxidation protein products-BSA,
      which indicated that protective effects of captopril are not related to
      sulfhydryl group.

PMID- 18334255
TI  - Alanine scanning mutagenesis of anti-TRAP (AT) reveals residues involved in
      binding to TRAP.
AB  - The trp RNA-binding attenuation protein (TRAP) regulates expression of the
      tryptophan biosynthetic (trp) genes in response to changes in intracellular
      levels of free l-tryptophan in many Gram-positive bacteria. When activated by
      binding tryptophan, TRAP binds to the mRNAs of several genes involved in
      tryptophan metabolism, and down-regulates transcription or translation of these
      genes. Anti-TRAP (AT) is an antagonist of TRAP that binds to tryptophan-activated
      TRAP and prevents it from binding to its RNA targets, and thereby up-regulates
      trp gene expression. The crystal structure shows that AT is a cone-shaped trimer
      (AT(3)) with the N-terminal residues of the three subunits assembled at the apex
      of the cone and that these trimers can further assemble into a dodecameric
      (AT(12)) structure. Using alanine-scanning mutagenesis we found four residues,
      all located on the "top" region of AT(3), that are essential for binding to TRAP.
      Fluorescent labeling experiments further suggest that the top region of AT is in
      close juxtaposition to TRAP in the AT-TRAP complex. In vivo studies confirmed the
      importance of these residues on the top of AT in regulating TRAP mediated gene
      regulation.

PMID- 18334256
TI  - Temporal and spatial changes of total and labile metal concentration in the
      surface sediments of the Vigo Ria (NW Iberian Peninsula): influence of
      anthropogenic sources.

PMID- 18334257
TI  - Physiological responses of the seagrass Posidonia oceanica as indicators of fish
      farm impact.
AB  - The development of aquaculture along the Mediterranean coastline degrades the
      marine environment, in particular Posidonia oceanica meadows, which, in extreme
      cases, show high mortality. Here we studied the effects of organic matter and
      nutrient input from the effluents of three fish farms, located along the
      Mediterranean coast, on P. oceanica physiology. For this purpose, we measured
      physiological variables such as total nitrogen (N) content, free amino acid (FAA)
      concentration and composition, N stable isotope ratio (delta 15N), total
      phosphorus (P) content and total non-structural carbohydrate (TNC) content in
      plant tissues and epiphytes affected by organic discharges (highly impacted
      stations: HI, and less impacted stations: LI) and compared these results with
      those obtained in references sites (control stations: C). For all the descriptors
      analyzed in P. oceanica epiphytes, the values recorded in the vicinity of cages
      were, in general, much higher than those in C. Leaves did not respond
      consistently in any case. Total N content and delta 15N in epiphytes together
      with the total P content in rhizomes and epiphytes were the physiological
      descriptors that showed the most consistent responses to fish farm effluents. On
      the basis of these observations, we conclude that fish farm activities strongly
      affect the physiological parameters of nearby P. oceanica meadows. We propose
      that changes in these physiological parameters may be useful indicators of marine
      environmental degradation in studies that monitor the effects of fish farming.

PMID- 18334258
TI  - Biologically active tetralones from New Caledonian Zygogynum spp.
AB  - Bioassay guided purification of the ethyl acetate extracts of the bark and leaves
      of five New Caledonian Zygogynum species (Winteraceae) led to the isolation and
      characterization of four phenyl-3-tetralones (3,4-dihydronaphthalen-1(2H)-one).
      Their structures were determined by various NMR techniques and chemical studies.
      The absolute configuration of the compounds was established by circular
      dichroism. The compounds showed binding affinity for peroxisome proliferator
      activated receptor-gamma (PPAR-gamma) and significant inhibitory activity against
      KB cancer cell line.

PMID- 18334259
TI  - Muscarinic receptor binding activity of polyoxygenated flavones from Melicope
      subunifoliolata.
AB  - The bark extract of Melicope subunifoliolata (Stapf) T.G. Hartley showed
      competitive muscarinic receptor binding activity. Six polymethoxyflavones
      [melibentin (1); melisimplexin (3); 3,3',4',5,7-pentamethoxyflavone (4);
      meliternatin (5); 3,5,8-trimethoxy-3',4',6,7-bismethylenedioxyflavone (6); and
      isokanugin (7)] and one furanocoumarin [5-methoxy-8-geranyloxypsoralen (2)] were
      isolated from the bark extract. Compounds 2 and 6 were isolated for the first
      time from M. subunifoliolata. The methoxyflavones (compounds 1, 3, 4, 5, 6, and
      7) show moderate inhibition in a muscarinic receptor binding assay, while the
      furanocoumarin (compound 2) is inactive. The potency of the methoxyflavones to
      inhibit [(3)H]NMS-muscarinic receptor binding is influenced by the position and
      number of methoxy substitution. The results suggest these compounds are probably
      muscarinic modulators, agonists or partial agonists/antagonists.

PMID- 18334260
TI  - Salmonella in free-living exotic and native turtles and in pet exotic turtles
      from SW Spain.
AB  - We screened 78 native and 94 exotic turtles from natural ponds and 39 exotic pet
      turtles for presence of Salmonella, resulting with infection rates of 6.61%,
      6.4%, and 5.1%, respectively. Concurrent shedding of multiple serotypes of the
      bacteria was only detected in one pet turtle. Eleven isolates were obtained in
      free-living turtles, including serotypes commonly found in reptiles and also the
      serotype Typhimurium, which is commonly related to human infections. In pet
      turtles, the five serotypes isolated were different to those isolated in free
      living turtles and had been reported to cause reptile-associated salmonellosis in
      humans. These results confirm the risk of transmission of Salmonella from free
      living and pet turtles to humans, demanding the necessity of regulation of pet
      turtle trade in Europe.

PMID- 18334261
TI  - Uptake of PAHs into polyoxymethylene and application to oil-soot (lampblack)
      impacted soil samples.
AB  - Polyoxymethylene (POM) is a polymeric material used increasingly in passive
      sampling of hydrophobic organic contaminants such as PAHs and PCBs in soils and
      sediments. In this study, we examined the sorption behavior of 12 PAH compounds
      to POM and observed linear isotherms spanning two orders of magnitude of aqueous
      concentrations. Uptake kinetic studies performed in batch systems for up to 54 d
      with two different volume ratios of POM-to-aqueous phase were evaluated with
      coupled diffusion and mass transfer models to simulate the movement of PAHs
      during the uptake process and to assess the physicochemical properties and
      experimental conditions that control uptake rates. Diffusion coefficients of PAHs
      in POM were estimated to be well correlated with diffusants' molecular weights as
      D(POM) proportional, variant(MW)(-3), descending from 2.3 x 10(-10) cm(2) s(-1)
      for naphthalene to 7.0 x 10(-11) cm(2) s(-1) for pyrene. The uptake rates for
      PAHs with log K(ow)<5.8 were controlled by the POM phase and the hydrophobicity
      of PAH compounds. For more hydrophobic PAH compounds, the aqueous boundary layer
      played an increasingly important role in determining the overall mass transfer
      rate. The POM partitioning technique was demonstrated to agree well with two
      other procedures for measuring PAH soil-water distribution coefficients in oil
      soot (lampblack) containing soil samples.

PMID- 18334262
TI  - Verification of dioxin formation in a catalytic oxidizer.
AB  - Emissions and inlet concentrations of polychlorinated dibenzo-p-dioxins and
      dibenzofurans (PCDD/PCDF) have been measured from a catalytic oxidizer and a
      thermal oxidizer. The catalyst inlet temperature was 427 degrees C. The thermal
      oxidizer operating temperature was 791 degrees C. Data of the toxic dioxin and
      furan congeners are reported. Important results of this field study are: (1) the
      catalytic oxidizer in this study produced an increase in PCDD/PCDF congener
      concentration of almost 10-fold from the inlet to the outlet (stack), thus
      verifying results of a previous study that evaluated only PCDD/PCDF emissions.
      All congeners increased from inlet to the stack. (2) The thermal oxidizer had
      little effect on PCDD/PCDF levels. There was a decrease in four of the congeners
      and an increase in 13 congeners. (3) Ambient air was the main source of
      PCDD/PCDFs in the stack emissions of the thermal oxidizer in this study.
      Laboratory investigations are needed to understand how PCDD/PCDFs are formed (and
      emitted) under conditions of this study.

PMID- 18334263
TI  - Impacts of charcoal characteristics on sorption of polycyclic aromatic
      hydrocarbons.
AB  - Sorption of three polycyclic aromatic hydrocarbons (PAHs, phenanthrene,
      anthracene and pyrene) on three charcoals and their precursor substance (sawdust)
      was studied. The charcoals obtained by heating at 400 degrees C for different
      periods were different in chemical composition and structure. Sorption
      characteristics were described by a Polanyi-Dubinin-Manes model combined with
      poly-parameter linear free energy relationships. The results revealed that though
      partition could not be neglected for sawdust and charcoal containing large
      sawdust residue, adsorption controlled the sorption of PAHs on matured charcoals,
      where pi-pi electron donor-acceptor (EDA) exerted as the main molecular-scale
      interactions. Charring elevated partition coefficients (K(oc)) of the three PAHs
      more than one order of magnitude, which ranged from 10(5.74) to 10(6.58) on
      charcoals (for PAHs at equilibrium concentration C(e)=0.005S(w)). Adsorption
      increased with the aromaticity of the charcoals, however, polar aromatic
      structure may stimulate sorption of PAHs due to the presence of pi-pi EDA
      interactions.

PMID- 18334264
TI  - Fluorotelomer alcohols induce hepatic vitellogenin through activation of the
      estrogen receptor in male medaka (Oryzias latipes).
AB  - Here we report on the in vivo estrogenic effects of two fluorotelomer alcohols,
      such as 1H,1H,2H,2H-perfluorooctan-1-ol (6:2 FTOH) and 1H,1H,2H,2H-perfluorodecan
      1-ol (8:2 FTOH), in male medaka (Oryzias latipes). An in vitro yeast two-hybrid
      assay indicated a significant, dose-dependent interaction between medaka estrogen
      receptor alpha (ERalpha) and coactivator TIF2 upon treatment with 6:2 FTOH, 8:2
      FTOH or 2,2,3,3,4,4,5,5,6,6,7,7,8,8,9,9,10,10,10-nonadecafluoro-1-decanol (NFDH).
      The relative ranks of tested chemicals on the estrogenic effects for medaka
      ERalpha descended in the order of estradiol-17beta (100)>>6:2 FTOH (0.16)>NFDH
      (0.016)>8:2 FTOH (0.0044). In contrast, no interaction with the ERalpha was
      observed upon treatment with perfluorooctane sulfonate (PFOS), perfluorooctanoic
      acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDA) or
      perfluoroundecanoic acid (PFUnDA). Expression analysis of hepatic vitellogenin
      (VTG) protein showed estrogenic potentials with, 6:2 FTOH and 8:2 FTOH,
      indicative of the induction of VTG synthesis in the livers of male medaka. We
      also investigated mRNA expression levels of two ER subtypes (ERalpha and beta)
      and two VTGs (VTG I and VTG II) in the livers of male medaka following exposure
      to FTOHs. Quantitative real-time polymerase chain reaction analyses revealed that
      hepatic ERalpha, VTG I, and VTG II mRNA responded rapidly to FTOHs such as 6:2
      FTOH and 8:2 FTOH after 8-h exposure, whereas no effects of these compounds on
      ERbeta mRNA transcription were observed. These results from both in vitro and in
      vivo assays strongly suggest that certain FTOHs, such as 6:2 FTOH and 8:2 FTOH,
      induce hepatic VTG through activation of ERalpha in male medaka.

PMID- 18334265
TI  - Photolysis of low concentration H2S under UV/VUV irradiation emitted from
      microwave discharge electrodeless lamps.
AB  - The photolysis of simulating low concentration of hydrogen sulfide malodorous gas
      was studied under UV irradiation emitted by self-made microwave discharge
      electrodeless lamps (i.e. microwave UV electrodeless mercury lamp (185/253.7 nm)
      and iodine lamp (178.3/180.1/183/184.4/187.6/206.2 nm)). Experiments results
      showed that the removal efficiency (eta H2S) of hydrogen sulfide was decreased
      with increasing initial H2S concentration and increased slightly with gas
      residence time; H2S removal efficiency was decreased dramatically with enlarged
      pipe diameter. Under the experimental conditions with pipe diameter of 36 mm, gas
      flow rate of 0.42 standard l s(-1), eta H2S was 52% with initial H2S
      concentration of 19.5 mg m(-3) by microwave mercury lamp, the absolute removal
      amount (ARA) was 4.30 microg s(-1), and energy yield (EY) was 77.3 mg kW h(-1);
      eta H2S was 56% with initial H2S concentration of 18.9 mg m(-3) by microwave
      iodine lamp, the ARA was 4.48 microg s(-1), and the EY was 80.5mg kW h(-1). The
      main photolysis product was confirmed to be SO4(2-) with IC.

PMID- 18334266
TI  - Predicting personal exposure of pregnant women to traffic-related air pollutants.
AB  - As epidemiological studies report associations between ambient air pollution and
      adverse birth outcomes, it is important to understand determinants of exposures
      among pregnant women. We measured (48-h, personal exposure) and modeled (using
      outdoor ambient monitors and a traffic-based land-use regression model) NO,
      NO(2), fine particle mass and absorbance in 62 non-smoking pregnant women in
      Vancouver, Canada on 1-3 occasions during pregnancy (total N=127). We developed
      predictive models for personal measurements using modeled ambient concentrations
      and individual determinants of exposure. Geometric mean exposures of personal
      samples were relatively low (GM (GSD) NO=37 ppb (2.0); NO(2)=17 ppb (1.6);
      'soot', as filter absorbance=0.8 10(-5) m(-1) (1.5); PM(2.2)=10 microg m(-3)
      (1.6)). Having a gas stove (vs. electric stove) in the home was associated with
      exposure increases of 89% (NO), 44% (NO(2)), 20% (absorbance) and 35% (fine PM).
      Interpolated concentrations from outdoor fixed-site monitors were associated with
      all personal exposures except NO(2). Land-use regression model estimates of
      outdoor air pollution were associated with personal NO and NO(2) only. The
      effects of outdoor air pollution on personal samples were consistent, with and
      without adjustment for other individual determinants (e.g. gas stove). These
      findings improve our understanding of sources of exposure to air pollutants among
      pregnant women and support the use of outdoor concentration estimates as proxies
      for exposure in epidemiologic studies.

PMID- 18334267
TI  - Increased procoagulant cell-derived microparticles (C-MP) in splenectomized
      patients with ITP.
AB  - BACKGROUND: Splenectomy is frequently employed for therapeutic and diagnostic
      purposes in various clinical disorders. However its long-term safety is not well
      elucidated. Although risk of infection by encapsulated organisms is widely
      recognized, less well-known are risks of thrombosis and cardiovascular disease.
      METHODS: We investigated levels of cell-derived microparticles (C-MP) in 23
      splenectomized ITP (ITP-S) and 53 unsplenectomized ITP patients (ITP-nS). Assay
      of C-MP derived from platelets (PMP), leukocytes (LMP), red cells (RMP) and
      endothelial cells (EMP) were performed by flow cytometry. Coagulation parameters
      included PT, aPTT and activities of FVIII, IX and XI. Results of all measures
      were compared between the two groups, ITP-S vs ITP-nS. RESULTS: Levels of all C
      MP were higher in ITP-S than ITP-nS but only RMP and LMP reached statistical
      significance (p = 0.0035 and p < 0.0001, respectively). The aPTT was
      significantly shorter in ITP-S (p = 0.029). Interestingly, correlation analysis
      revealed that RMP, but not other C-MP, were associated with shortening of aPTT (p
      = 0.024) as well as with increased activities of factors VIII (p = 0.023), IX (p
      = 0.021) and XI (p = 0.0089). CONCLUSIONS: RMP and LMP were significantly
      elevated in splenectomized compared to non-splenectomized ITP patients. This
      suggests that the spleen functions to clear procoagulant C-MP, and that elevation
      of C-MP might contribute to increased risk of thrombosis, progression of
      atherosclerosis and cardiovascular disease following splenectomy.

PMID- 18334268
TI  - Epigenetics--new frontiers in neuroendocrinology.

PMID- 18334269
TI  - Nitric oxide activation and reduction by heme-copper oxidoreductases and nitric
      oxide reductase.
AB  - The understanding of the dynamics and conformational control involved in the
      interplay between structure and function of nitric oxide reductase (Nor) and heme
      copper oxidoreductases in their function to convert nitric oxide (NO) to nitrous
      oxide (N2O) is of fundamental importance in bioenergetics. We have applied
      resonance Raman spectroscopy to investigate the NO ligation/deligation reactions
      and the extent of communication between the metal centers at the heme a3-CuB site
      of heme-copper oxidases and of the heme Fe-non-heme Fe in Nor. The present study
      provides information of the electronic and vibrational structure of
      intermediates, and thus, it forms the basis for an atomic-level description of
      the key steps in the N-N bond formation and the N-O bond cleavage mechanism. The
      present experiments provide evidence as to the validity of the proposed
      hypothesis of the common evolutionary origin of aerobic respiration and bacterial
      denitrification.

PMID- 18334270
TI  - Parental maltreatment and proximal risk factors using the Childhood Experience of
      Care & Abuse (CECA) instrument: a life-course study of adult chronic depression -
      5.
AB  - BACKGROUND: This is the final paper of a series concerning parental maltreatment
      and chronic depression in women. It extends the scope of the analysis to take
      account of proximal risk factors, present within at most six months of an onset.
      It deals with the contribution of factors influencing onset of a depressive
      episode as well as those related to whether this takes a chronic course. Once a
      two-stage model dealing with both sets of risk factors has been developed we
      explore how far distal factors (more than at least one year earlier) influence
      each stage. METHODS: Three studies are employed. All take account of parental
      maltreatment. Two prospective studies deal with proximal risk factors, and a
      retrospective one with distal and proximal factors. RESULTS: For the first stage
      of the model concerning onset the influence of parental maltreatment and its
      correlated risk factors (e.g. conduct problems) are almost entirely mediated by
      proximal factors (e.g. quality of core relationships). However, for the second
      stage concerning course parental maltreatment makes a direct contribution that is
      independent of all other risk factors. LIMITATIONS: The retrospective nature of
      some of the data may introduce bias (But see the second paper in the present
      series [Brown, G.W., Craig, T.K.J., Harris, T.O., Handley, R.V., Harvey, A.L.,
      2007b. Validity of retrospective measures of early maltreatment and depressive
      episodes using the Childhood Experience of Care & Abuse (CECA) instrument - a
      life-course study of adult chronic depression - 2. J. Affect. Dis., 103, 217
      224]). Only females have been considered. CONCLUSIONS: The influence of parental
      maltreatment on the onset of adult depression is largely indirect and the
      mechanisms involved are reasonably clear. However, the mechanisms involved in the
      substantial direct contribution of maltreatment to course are as yet unclear.
      Some interplay of maltreatment and early brain development is one of a number of
      interesting possibilities.

PMID- 18334271
TI  - Association of serotonin-1A and 2A receptor promoter polymorphisms with
      depressive symptoms and functional recovery in elderly persons after hip
      fracture.
AB  - BACKGROUND: Depression is common after hip fracture and is associated with poorer
      functional recovery. Polymorphisms of the serotonin 1a (5HTR1A) and 2a receptors
      (5HTR2A) are associated with depression; therefore, we examined their association
      with depressive symptoms and functional recovery after hip fracture. METHODS: 145
      elderly women were followed for 12 months after hip fracture. Depressive symptoms
      were measured with the 15-item Geriatric Depression Scale (GDS). Functional
      status was measured by Lower Extremity Physical and Instrumental Activity of
      Daily Living scales (LPADLs and IADLs). Time-adjusted general linear regression
      models compared mean GDS between those with and without risk alleles for 5HTR1A
      and 5HTR2A. RESULTS: Women with 1-2 copies of the 5HTR1A (-1019) G allele had
      higher GDS scores (Adjusted Mean Difference=0.59; 95% CI, 0.12-1.06), and poorer
      IADL scores (Adjusted Mean Difference=0.24; 95%CI -0.002 to 0.49), compared to
      those without this allele, controlling for potential confounders and 5HTR2A.
      Depressive symptoms partly accounted for poorer IADL recovery. Women with 1-2
      copies of the 5HTR2A (-1438) C allele did not have significantly higher GDS
      scores (Adjusted Mean Difference=0.34; 95%CI, -0.20 to 0.87) and had better IADL
      scores (Adjusted Mean Difference=-0.40; 95%CI -0.74 to 0.06) than those with A/A
      genotype. LIMITATIONS: The findings are limited by small sample size and the use
      of a screening scale to measure depression. CONCLUSIONS: The 5HTR1A (-1019) G
      allele is associated with increased depressive symptoms after hip fracture, which
      in turn accounts for poorer functional recovery. These results suggest a role for
      serotonergic genetic variation in elderly persons' resilience and recovery from
      medical events.

PMID- 18334272
TI  - Implications of the DSM's emphasis on sadness and anhedonia in major depressive
      disorder.
AB  - At least five symptoms must occur for a DSM diagnosis of major depressive
      disorder (MDD), one of which must be sadness or anhedonia. The present study is
      the first known investigation of the implications of the presence or absence of
      these prioritized symptoms on symptom expression and clinical characteristics
      among 564 young adults with MDD. Differences in symptom expression and clinical
      characteristics occurred among MDD participants with sadness relative to those
      without sadness as well as among MDD participants with anhedonia relative to
      those without anhedonia. Differential symptom expression could have important
      implications for the etiology, prevention, and treatment of MDD.

PMID- 18334273
TI  - Hypofractionated stereotactic radiotherapy for medically inoperable stage I non
      small cell lung cancer--report on clinical outcome and dose to critical organs.
AB  - We report 20 cases using hypofractionation stereotactic radiotherapy in medically
      inoperable stage I non-small cell lung cancer with dose escalation of 45-54 Gy
      prescribed at 85 or 90% isodose level in 3-4 fractions. Two-year local control
      and cancer-specific survival were 94.7 and 77.6%, respectively, with minimal
      toxicity. Though, large fraction size can be safely given to peripheral lung
      tumors, normal tissue tolerance to hypofractionated radiotherapy to esophagus,
      trachea, main bronchi, aorta and heart remains unknown. Therefore we also
      reported the maximum point doses to these critical organs to contribute
      information to extend this technique to more centrally located lung tumors in
      future.

PMID- 18334274
TI  - Application of active breathing control in 3-dimensional conformal radiation
      therapy for hepatocellular carcinoma: the feasibility and benefit.
AB  - BACKGROUND AND PURPOSE: To investigate the feasibility and effectiveness of
      utilizing active breathing coordinator (ABC) in 3DCRT for HCC. MATERIALS AND
      METHODS: A dosimetric comparison between the free-breathing (FB) plan and ABC
      plan in HCC 3DCRT was performed. Set-up errors and reproducibility of diaphragm
      position using ABC were measured, and patients' acceptance was also recorded.
      RESULTS: From April 2005 to February 2007, 28 HCC were irradiated with ABC and
      they tolerated ABC well. The mean dose to normal liver was reduced from 16.9Gy in
      FB plan to 14.3Gy in ABC plan. PTV for ABC and FB plans were 529cm(3) and
      781cm(3), respectively, and V(23) were reduced from 45% to 30%. The predicted
      incidences of radiation-induced liver disease by Lyman model were 1% and 2.5%,
      respectively, in favor of ABC plan. The systematic and random errors for the ABC
      and FB plans were 1.2mm vs. 4.7mm, 1.6mm vs. 3.5mm, and 1.8mm vs. 2.7mm,
      respectively, in cranio-caudal, anterior-posterior, and left-right directions.
      The average intrafraction reproducibility of diaphragm position in cranio-caudal
      direction was 1.6mm, and the interfraction, 6.7mm. CONCLUSIONS: The utilization
      of ABC in HCC 3DCRT is feasible, and can reduce liver irradiation.

PMID- 18334275
TI  - Non-invasive evaluation of liver fibrosis using transient elastography.
AB  - Transient elastography (TE, FibroScan) is a novel non-invasive method that has
      been proposed for the assessment of hepatic fibrosis in patients with chronic
      liver diseases, by measuring liver stiffness. TE is a rapid and user-friendly
      technique that can be easily performed at the bedside or in the outpatient clinic
      with immediate results and good reproducibility. Limitations include failure in
      around 5% of cases, mainly in obese patients. So far, TE has been mostly
      validated in chronic hepatitis C, with diagnostic performance equivalent to that
      of serum markers for the diagnosis of significant fibrosis. Combining TE with
      serum markers increases diagnostic accuracy and as a result, liver biopsy could
      be avoided for initial assessment in most patients with chronic hepatitis C. This
      strategy warrants further evaluation in other aetiological types of chronic liver
      diseases. TE appears to be an excellent tool for early detection of cirrhosis and
      may have prognostic value in this setting. As TE has excellent patient acceptance
      it could be useful for monitoring fibrosis progression and regression in the
      individual case, but more data are awaited for this application. Guidelines are
      needed for the use of TE in clinical practice.

PMID- 18334276
TI  - Towards more efficient testing strategies--analyzing the efficiency of toxicity
      data requirements in relation to the criteria for classification and labelling.
AB  - This contribution is based on the assumption that the aim of toxicity testing as
      required by chemicals legislation is to identify as many chemicals of concern to
      human health and the environment as possible, given a limited amount of resources
      allocated to testing. Based on this assumption we propose a method for the
      optimization of test systems for industrial chemicals, based on the calculation
      of efficiency ratios for tests and test systems. The efficiency ratio of a
      toxicity test depends on the monetary cost of performing the test and the
      probability that the test will identify a chemical of concern, as estimated by
      the rules for classification and warning labelling. Efficiency ratios are
      estimated based on the results of basic standardized toxicity testing for acute
      toxicity, subacute toxicity, irritation and sensitization of 1409 industrial
      chemicals notified in the European Union between 1994 and 2004. This careful
      evaluation of the regulatory consequences of testing indicated that many of these
      substances are classified based on short-term testing of acute toxicity,
      irritation and sensitization and that most of the substances classified due to a
      28-day study were also classified based on short-term testing. These results
      indicate that, within the classification and labelling system, it is currently
      more efficient to perform short-term testing of a larger number of substances
      rather than to perform subacute toxicity studies on substances already tested for
      acute toxicity.

PMID- 18334277
TI  - Radiocaesium contamination of beef in Croatia after the Chernobyl accident.
AB  - Long-term investigations of radiocaesium activity concentrations in beef in the
      Republic of Croatia are presented. The radiocaesium levels in beef decreased
      exponentially and the effective ecological half-life of 137Cs was estimated to be
      0.57+/-0.06 years for 1986-1990 period and 5.21+/-0.27 years for the 1991-2005
      period. For 1986-1990 period, the effective ecological half-life of 134Cs in was
      estimated to be about 0.69+/-0.05 while 134Cs activity concentrations after year
      1990 were below the detection limit of the instruments. The 134Cs:137Cs activity
      ratio in beef has been found to be similar to the ratio that has been observed in
      other foodstuffs and environmental samples. Radioecological sensitivity for beef
      meat, i.e., the transfer coefficient from fallout to sample was estimated to be
      1.15x 10(-2)Bqykg(-1)/(Bqm(-2)). For an adult member of Croatian population
      annual effective doses received by 134Cs and 137Cs intake due to consumption of
      beef are small, as per caput effective dose for the overall 1986-2005 period was
      estimated to be 24.6microSv. Consequently, after the Chernobyl accident beef
      consumption was not a critical pathway for the transfer of radiocaesium from
      fallout to humans in Croatia.

PMID- 18334278
TI  - In silico assessment of toxicity of heat-generated food contaminants.
AB  - Since the discovery of acrylamide in heat-treated carbohydrate-rich foods, many
      more heat-generated food contaminants have been identified in a variety of foods
      and models systems. A database of these contaminants, generated as a result of
      either lipid oxidation or the Maillard reaction, has recently been compiled under
      the HEATOX project. A large majority of the compounds has not been tested for
      potential adverse effects on human health, which makes it difficult to carry out
      adequate assessment of risks to an average consumer. This study used two in
      silico toxicity Expert Systems (Topkat and Derek for Windows), as a preliminary
      screening tool to identify potential toxicants among the heat-generated
      contaminants in foods or model systems. The methodology enabled prioritisation of
      the compounds on the basis of predicted toxicities, and identification of
      potential toxicants for targeted testing by standard laboratory procedures. A
      comparison between the predicted toxicities of selected compounds and the
      available experimental data indicated that the methodology can be reliably used
      for assessing toxicity of untested food contaminants.

PMID- 18334279
TI  - Bioactive properties and chemical composition of six walnut (Juglans regia L.)
      cultivars.
AB  - The chemical composition, antioxidant potential and antimicrobial activity were
      studied in six walnuts (Juglans regia L.) cultivars (cv. Franquette, Lara,
      Marbot, Mayette, Mellanaise and Parisienne) produced in Portugal. Concerning
      their chemical composition the main constituent of fruits was fat ranging from
      78.83% to 82.14%, being the nutritional value around 720kcal per 100g of fruits.
      Linoleic acid was the major fatty acid reaching the maximum value of 60.30% (cv.
      Lara) followed by oleic, linolenic and palmitic acids. The aqueous extracts of
      walnut cultivars were investigated by the reducing power assay, the scavenging
      effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals and beta-carotene
      linoleate model system. All the walnut extracts exhibited antioxidant capacity in
      a concentration-dependent manner being the lowest EC(50) values obtained with
      extracts of cv. Parisienne. Their antimicrobial capacity was also checked against
      gram positive (Bacillus cereus, Bacillus subtilis, Staphylococcus aureus) and
      gram negative bacteria (Pseudomonas aeruginosa, Escherichia coli, Klebsiella
      pneumoniae) and fungi (Candida albicans, Cryptococcus neoformans), revealing
      activity against the different tested microorganisms.

PMID- 18334280
TI  - Proteomics-based identification of autoantibody against heat shock protein 70 as
      a diagnostic marker in esophageal squamous cell carcinoma.
AB  - Detection of novel tumor-related antigens and autoantibodies in cancer patients
      is expected to facilitate the diagnosis of early-stage malignant tumor and
      establish effective new immunotherapies. The purpose of this study was to
      identify novel tumor antigens in an esophageal squamous cell carcinoma (ESCC)
      cell line (TE-2) and related autoantibodies in sera from patients with ESCC using
      a proteomics-based approach. TE-2 proteins were separated by two-dimensional
      polyacrylamide gel electrophoresis, followed by Western blot analysis in which
      sera from patients with ESCC, healthy controls and patients with other cancers
      were tested for primary antibodies. Positive spots were excised from silver
      stained gels and analyzed by matrix-assisted laser disorption/ionization time-of
      flight mass spectrometry (MALDI-TOF/TOF-MS). Sera from patients with ESCC yielded
      multiple spots, one of which was identified as heat shock protein 70 (Hsp70) by
      MALDI-TOF/TOF-MS. Concentrations of serum Hsp70 autoantibody were significantly
      higher for patients with ESCC (mean, 0.412+/-0.096 mg/ml) than for patients with
      gastric (0.236+/-0.112 mg/ml, P<0.001) or colon cancer (0.231+/-0.120 mg/ml,
      P<0.001) or healthy individuals (0.207+/-0.055 mg/ml, P<0.001) by enzyme-linked
      immunosorbent assay. We have identified an autoantibody against Hsp70 in ESCC
      patients. The proteomic approach implemented herein offers a powerful tool for
      identifying novel serum markers that may display clinical utility against cancer.

PMID- 18334281
TI  - E2F1 in gliomas: a paradigm of oncogene addiction.
AB  - Cancer arises as a result of a stepwise accumulation of genetic changes. One of
      these changes, deregulation of the Rb/E2F1 pathway resulting from alterations in
      members of the pathway, is a hallmark of all human cancers. These mutations
      promote tumor development by deregulating the E2F family of transcription
      factors, which results in uncontrolled cell cycle progression. The E2F1 protein
      functions as a transcription factor that enhances cell proliferation by binding
      to the promoter region of several genes, including those that are involved in
      cell cycle regulatory activities and DNA replication. It is now becoming clear
      that the role of E2F1 in regulating transcription and cell growth is also highly
      dependent on the cellular context. This complexity is also evident from analyses
      of perturbations in E2F-modulated tumor development. For example, deregulated
      E2F1 expression can either promote or inhibit tumorigenesis depending on the
      nature of the other oncogenic mutations that are present. This explains the
      ability of E2F1 to behave as both an oncogene and tumor suppressor gene. Here we
      focus on reviewing the most recent evidence supporting the "addiction" of gliomas
      to this versatile transcription factor. We also consider the clinical relevance
      of this by examining the role of E2F1 as a prognosis factor and as a target for
      the development of novel strategies.

PMID- 18334282
TI  - Expression of LAPTM4B-35: a novel marker of progression, invasiveness and poor
      prognosis of extrahepatic cholangiocarcinoma.
AB  - LAPTM4B was proven to overexpress in hepatocellular carcinoma and relate to
      differentiation. We immunohistochemically investigated the expression and
      potential clinicopathological and prognostic significance of LAPTM4B encoded
      protein, LAPTM4B-35, in extrahepatic cholangiocarcinoma (EHCC) for specimens from
      consecutive 81 patients. LAPTM4B-35 staining was positive in cancer tissues from
      59 patients (72.8%), including 12 with score 1, 22 with score 2 and 25 with score
      3. No positive staining was found in non-cancer epithelia. The staining score in
      cancer tissues was not only significantly associated with TNM staging,
      histological grade, perineural and lymph node invasion (P<0.05), but also of
      comprehensive prognostic implications, including integrated estimation with CA19
      9. These data established that LAPTM4B-35 positively expressed in a great portion
      of EHCC and might be a novel molecular maker of progression, invasiveness and
      poor prognosis.

PMID- 18334283
TI  - Improving prediction of "inevitable" surgery during non-surgical treatment of
      sciatica.
AB  - A randomized trial showed that surgery speeds up recovery of patients suffering
      sciatica for 6 weeks but prolonged conservative care yields similar results at
      one year. However 39% of this conservative care group ultimately underwent
      surgery after a mean period of 18.7 weeks. We evaluated variables to improve
      prediction of surgery in the conservatively treated cohort. Baseline data on 142
      patients enroled in the conservative treatment arm of a randomized trial were
      analyzed to select those that could contribute to the prediction of surgery. The
      actual occurrence of surgery was used as dependent outcome of interest. Variables
      measured at baseline included neurological examination results, the visual
      analogue scale for pain (VAS) and the Roland disability questionnaire (RDQ).
      Higher pain intensity and functional limitations at baseline were associated with
      an increased likelihood of surgery during follow-up. Mutually adjusted Odds
      Ratios of 1.7 (95% CI; 1.1-2.7) per 20mm incremental intensification of pain on
      the VAS score and 1.8 (95% CI; 1.2-2.9) per 3 points of deterioration of the RDQ
      score quantify the increasing chance of undergoing delayed surgery. Despite
      maximal efforts to the contrary, surgery could not be prevented for a
      considerable proportion of patients in a conservatively treated cohort. Compared
      to those with lower scores initially, patients with more intense leg pain or
      higher disability scores were at higher risk to undergo delayed surgery. The
      individual surgical decision process is facilitated by the use of pain and
      disability scales complemented by patient preferences.

PMID- 18334284
TI  - Hypoxia in prostate cancer: a powerful shield against tumour destruction?
AB  - Tumour hypoxia is progressively emerging as a common feature of prostate tumours
      associated with poor prognosis. While the molecular basis of disease progression
      is increasingly well documented, the potential role of hypoxia in these processes
      remains poorly evaluated. By dissecting the impact of hypoxia-inducible factor 1
      alpha on molecular responses, this review provides evidence for a powerful
      protecting role of oxygen deprivation against oxidative stress injury, androgen
      deprivation, chemotherapeutic and radiation cytotoxicity. We propose hypoxia as a
      potent tumour-induced shield against destruction and suggest its targeting may
      need to be routinely addressed in the management of prostate cancer.

PMID- 18334285
TI  - The "metabolovirus" model of hepatitis B virus suggests nutritional therapy as an
      effective anti-viral weapon.
AB  - Hepatitis B virus (HBV) is a small DNA virus that targets the liver almost
      exclusively. Chronic infection with HBV might lead to severe liver-related
      pathologies including chronic hepatitis, cirrhosis and hepatocellular carcinoma.
      Based on its enhancer composition, which links nutritional signals that control
      hepatic glucose and fat metabolism in the liver to HBV gene expression and
      replication, it appears that the virus has adopted a regulatory system that is
      unique to the major hepatic metabolic genes. This unique virus-host interaction,
      mediated by metabolic events in the liver, is designated by us the "metabolovirus
      model". We hypothesize that by mimicking the expression of key genes implicated
      in glucose homeostasis, HBV sophisticatedly exploits the host resources to ensure
      its persistence. Specifically, by recruiting transcription factors and
      coactivators common to essential hepatic metabolic genes the virus avoids a
      possible resistance by its host, on the one hand, and ensures a timely and proper
      response to changes in its environment in terms of metabolic milieu, on the other
      hand. Furthermore, by coupling its gene expression to the expression of hepatic
      metabolic genes that fluctuate during the day, we predict a fluctuating nature of
      HBV gene expression. This can serve the virus in its attempts to escape the host
      immune system in addition to other immune evading strategies adopted by the
      virus, such as the secretion of the e antigen. Based on our "metabolovirus
      model", we suggest new mechanisms to previously unexplained clinical phenomena,
      such as the observed diversity in disease severity between different geographical
      areas that differ in nutritional habits. Furthermore, given the up-regulatory
      effect of food deprivation on HBV gene expression and replication, we suggest
      that conditions of short-term starvation should be completely avoided by HBV
      infected individuals, and dietary recommendations such as the ingestion of
      complex carbohydrates before sleep should be adopted. Thus, our hypothesis sets
      the stage for viral manipulation by controlling food intake, and opens additional
      avenues towards food or nutritional therapy as an effective anti-HBV weapon.

PMID- 18334286
TI  - Molluscicidal activity against Oncomelania hupensis of Ginkgo biloba.
AB  - In search for molluscicidal active components, petroleum ether, ethyl acetate,
      ethanol, and water extracts from Ginkgo sarcotesta were evaluated against the
      snail Oncomelania hupensis. The bioassay-oriented showed that the activity
      concentrates in the petroleum ether extract (LD(50) 7.81 ppm). Ginkgolic acids,
      isolated from the petroleum ether extract, exhibited strong molluscicidal
      activity (LD(50) 1.49 ppm), gingkgolic acid C15:1 having the strongest
      molluscicidal activity.

PMID- 18334287
TI  - Glycation associated skin autofluorescence and skin elasticity are related to
      chronological age and body mass index of healthy subjects.
AB  - Glycation is the non-enzymatic reaction between reducing sugars and proteins that
      leads to the formation of advanced glycation end products (AGEs). In vivo skin
      autofluorescence (lambda(ex)/lambda(em)=370/440 nm) was used as a non-invasive
      clinical tool to study skin AGE accumulation in healthy panellists. Using
      multiple linear regression analysis, it was shown that for panellists below the
      age of 40, glycation associated in vivo skin fluorescence intensity increased as
      a function of chronological age and body mass index (BMI). Above the age of 40,
      the fluorescence was associated to age but not to BMI, suggesting that the effect
      of age became dominant over BMI. Since the accumulation of AGEs is expected to
      affect the biomechanical properties of the skin, in vivo skin elasticity data
      were gathered on a second panel. It was found that skin elasticity depended on
      age and BMI in a similar fashion as to what we observed for the skin fluorescence
      data. It is hypothesised that skin AGE accumulation contributes to the loss of
      skin elasticity in aged and/or overweight people.

PMID- 18334288
TI  - Mapping of macrophage elastase cleavage sites in insoluble human skin elastin.
AB  - Macrophage elastase (MMP-12) is a member of the family of matrix
      metalloproteinases (MMPs) and is active against multiple extracellular protein
      substrates such as elastin. Its effect on elastin is central to emphysema in the
      lung and photoaging of skin. Its expression in the skin increases on photodamaged
      skin and upon aging. Detecting and characterizing peptides cleaved in elastin,
      therefore, helps to understand such degradative disease processes in the skin and
      is also needed to assist in the rational design of agents that specifically
      inhibit the degradation. In this study, cleavage sites of MMP-12 in human skin
      elastin were extensively investigated. The peptides formed as a result of
      cleavages by this enzyme in the human skin elastin were characterized using mass
      spectrometry. A total of 41 peptides ranging from 4 to 41 amino acids were
      identified and 36 cleavage sites were determined. Amino acids encoded by exons 5,
      6, 26, 28-31 were particularly susceptible to cleavages by MMP-12 and none or
      very few cleavages were detected from domains encoded by the remaining exons. The
      amino acid preferences of the different subsites on the catalytic domain of MMP
      12 were analyzed.

PMID- 18334289
TI  - Effect of clay pretreatment on photofermentative hydrogen production from olive
      mill wastewater.
AB  - The aim of this paper was to gain further insight into the effect of the clay
      pretreatment process on photofermentative hydrogen production. This two-stage
      process involved a clay pretreatment step followed by photofermentation which was
      performed under anaerobic conditions with the illumination by Tungsten lamps.
      Rhodobacter sphaeroides O.U.001 was used for photofermentation. Higher amounts of
      color (65%), total phenol (81%) and chemical oxygen demand (31%) removal
      efficiencies were achieved after clay pretreatment process. During
      photofermentative hydrogen production with the effluent of clay pretreatment
      process, the main organic compounds resulting higher hydrogen production rates
      were found to be acetic, lactic, propionic, and butyric acids. Compared to
      photofermentation using raw olive mill wastewater ( 16LH2/LOMW), the amount of
      photofermentative hydrogen production was doubled by using the effluent of the
      clay pretreatment process (31.5LH2/LOMW). The reasons for the improvement of
      hydrogen production by clay treatment can be attributed to the high removal of
      the hardly biodegradable compounds such as phenols; minor removal of organic
      acids, sugars and amino acids that are known to enhance photofermentative
      hydrogen production; and the color depletion of raw OMW which might cause a
      shadowing effect on the photosynthetic bacteria.

PMID- 18334290
TI  - Evaluation of different substrates to support the growth of Typha latifolia in
      constructed wetlands treating tannery wastewater over long-term operation.
AB  - The aim of this study was to investigate the performance of horizontal subsurface
      flow constructed wetlands planted with Typha latifolia treating tannery
      wastewater under long-term operation. Two expanded clay aggregates (Filtralite
      MR3-8-FMR and Filtralite NR3-8-FNR) and a fine gravel-FG were used as substrate
      for the constructed wetland units plus one unit with FMR was left as an
      unvegetated control. The systems were subject to three hydraulic loadings, 18, 8
      and 6cmd(-1), and to periods of interruption in the feed. The relationship
      between the substrate, plant development and removal efficiency, especially of
      organic matter, was investigated. Organic loadings up to 1800kg BOD(5)ha(-1)d(-1)
      and 3849kg COD ha(-1)d(-1) were applied leading to mass removals of up to 652kg
      BOD(5)ha(-1)d(-1) and 1869kg COD ha(-1)d(-1), respectively. The three different
      substrates were adequate for the establishment of T. latifolia, although the clay
      aggregates allowed for higher plant propagation levels. The units with FNR and
      FMR achieved significantly higher COD and BOD5 removal when compared to the FG
      and to the unplanted units. The systems proved to be tolerant to high organic
      loadings and to interruptions in feed suggesting this technology as a viable
      option for the biological treatment of tannery wastewater.

PMID- 18334291
TI  - Comparison of pretreatment strategies of sugarcane baggase: experimental design
      for citric acid production.
AB  - Solid state fermentation was carried out to compare efficiency of acid, alkaline
      and urea pretreatment of sugarcane bagasse for production of citric acid using
      Aspergillus niger ATCC 9142. Plackett-Burman statistical design was used to
      evaluate significance of variables. Pretreatment of bagasse by urea was known as
      the most influential treatment to increase citric acid production (137.6g/kg of
      dry sugarcane bagasse and citric acid yield of 96% based on sugar consumed).
      Finally, up scaling was achieved to a 20L solid state fermentor in which humidity
      was constant in gas phase and urea-treated sugarcane bagasse. The produced acid
      concentration and yield in fermentor was 82.38g/kg of dry substrate and
      26.45g/kgday, respectively.

PMID- 18334292
TI  - Heavy metal adsorbents prepared from the modification of cellulose: a review.
AB  - A number of industries currently produce varying concentrations of heavy metal
      laden waste streams with significant consequences for any receiving environmental
      compartment. In recent years, increasing emphasis has been placed on
      environmental impact minimisation and resulting from this the range and
      capability of natural and prepared materials capable of heavy metal removal has
      seen steady development. In particular considerable work has been carried out on
      the use of both natural materials and their modifications. These natural
      materials, in many instances are relatively cheap, abundant in supply and have
      significant potential for modification and ultimately enhancement of their
      adsorption capabilities. This review paper reviews the current state of research
      on the use of the naturally occurring material cellulose, its modified forms and
      their efficacy as adsorbents for the removal of heavy metals from waste streams.
      Adsorbents based on direct modification of cellulose are evaluated initially and
      subsequently modifications resulting from the grafting of selected monomers to
      the cellulose backbone with subsequent functionalisation are assessed. The heavy
      metal adsorption capacities for these modified cellulose materials were found to
      be significant and levels of uptake were comparable, in many instances, to both
      other naturally occurring adsorbent materials and commercial ion exchange type
      resins. Many of the modified cellulose adsorbents proved regenerable and re
      usable over a number of adsorption/desorption cycles allowing recovery of the
      adsorbed heavy metal in a more concentrated form.

PMID- 18334293
TI  - Pyrimidine-based inhibitors of CaMKIIdelta.
AB  - Non-ATP competitive pyrimidine-based inhibitors of CaMKIIdelta were identified.
      Computational studies were enlisted to predict the probable mode of binding. The
      results of the computational studies led to the design of ATP competitive
      inhibitors with optimized hinge interactions. Inhibitors of this class possessed
      improved enzyme and cellular activity compared to early leads.

PMID- 18334294
TI  - Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 1: SAR of the aryl
      region.
AB  - A family of aryl-substituted maleimides was prepared and studied for their
      activity against calmodulin dependant kinase. Inhibitory activities against the
      enzyme ranged from 34nM to >20microM and were dependant upon both the nature of
      the aryl group and the hydrogen bond donating potential of the maleimide ring.
      Key interactions with the kinase ATP site and hinge region were found to be
      consistent with homology modeling predictions.

PMID- 18334296
TI  - Synthesis and study of antiviral and anti-radical properties of aminophenol
      derivatives.
AB  - A number of sterically-hindered o-aminophenol derivatives have been synthesized,
      and their antiviral activity in parallel with reactivity towards commonly
      encountered free-radical intermediates was investigated. Of the compounds tested,
      the highest activity in suppressing replication of Herpes simplex type l viruses
      was displayed by N-acyl and N-aryl derivatives of 4,6-di-tert-butyl-2
      aminophenol, which were able to interact with organic free radicals and, at the
      same time, manifested low reactivity towards reactive oxygen species.

PMID- 18334295
TI  - Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 2: SAR of the amine
      tether.
AB  - A family of aryl-substituted maleimides was prepared and studied for their
      activity against calmodulin-dependant kinase. Inhibitory activities against the
      enzyme ranged from 34nM to >20microM and were dependant upon both the nature of
      the aryl group and the tether joining the basic amine to the indolyl maleimide
      core. Key interactions with the kinase ATP site and hinge region, predicted by
      homology modeling, were confirmed.

PMID- 18334297
TI  - Spontaneous third ventriculostomy.
AB  - Spontaneous ventriculostomy (SV) is a rare condition where there is a spontaneous
      communication between the ventricle and the subarachnoid space as a result of
      hydrocephalus. Only four cases of SV through the floor of the third ventricle
      have been previously reported. Two further cases are presented and the literature
      reviewed.

PMID- 18334298
TI  - Targeting regions with highest lipid content on MR spectroscopy may improve
      diagnostic yield in stereotactic biopsy.
AB  - Gliomas are heterogeneous brain tumors and prognosis and treatment are dependent
      on the highest histological grade present. Stereotactic biopsy is associated with
      an inherent risk of sampling error. Magnetic resonance spectroscopy (MRS) uses
      clinical MR scanners to provide chemical in addition to conventional information.
      MRS studies in brain tumors have found increased levels of choline-containing
      compounds (Cho) and decreased levels of N-acetylaspartate (NAA), creatine (Cr)
      and phosphocreatine (PCr) which are all associated with increased grade of
      glioma. We propose the use of MRS-guided stereotactic biopsy of astrocytomas to
      increase diagnostic yield and reduce the sampling error rate. MRS was performed
      on two patients undergoing stereotactic biopsy for suspected astrocytoma.
      Spectral peak heights of the metabolites Cho at 3.2 parts per million (ppm)
      chemical shift, NAA at 2.0 ppm and lipid (Lip) at 1.2 ppm, were measured. Biopsy
      targets were selected from the voxels with the highest Cho/NAA and normalised
      against Cho levels in the contralateral normal tissue, as well as those with
      highest lipid content. The biopsies were taken and tissue diagnosis was obtained
      via standard histological techniques. Histological grade was found to be
      different in one case: the region with a high Lip/Cr and Cho/NAA ratios showed
      glioblastoma, whereas the region with high Cho/NAA but low Lip/Cr ratios showed
      anaplastic astrocytoma. The second patient had high Cho/NAA ratio but low Lip/Cr
      ratio in both targets and the histology revealed anaplastic astrocytoma in both
      samples. MRS is a useful biomedical imaging tool for diagnosing and grading
      astrocytomas. Targeting regions with highest lipid content can potentially
      improve the diagnostic yield and minimize sampling error in stereotactic biopsy.

PMID- 18334299
TI  - Tetramic and tetronic acids: an update on new derivatives and biological aspects.
AB  - Significant developments in the isolation of tetramic acids and tetronic acids,
      in the elucidation of their biosyntheses and their biological activities and in
      laboratory syntheses are reviewed with a focus on those derivatives with
      medicinal and pharmacological relevance. Important new members of the title
      compound families isolated since the year 2000 are covered as well as new
      biological aspects of some earlier congeners.

PMID- 18334300
TI  - Expanding the repertoire of small molecule transcriptional activation domains.
AB  - Molecules that can reconstitute the function of transcriptional activators hold
      enormous potential as therapeutic agents and as mechanistic probes. Previously we
      described an isoxazolidine bearing functional groups similar to natural
      transcriptional activators that up-regulates transcription 80-fold at 1 microM in
      cell culture. In this study, we analyze analogs of this molecule to define key
      characteristics of small molecules that function as transcriptional activation
      domains in cells. Conformational rigidity is an important contributor to function
      as is an overall amphipathic substitution pattern. Using these criteria, we
      identified additional molecular scaffolds with excellent (approximately 60-fold)
      activity as transcriptional activation domains. These results point the way for
      the creation of new generations of small molecules with this function.

PMID- 18334301
TI  - Mx1 causes resistance against influenza A viruses in the Mus spretus-derived
      inbred mouse strain SPRET/Ei.
AB  - Inbred SPRET/Ei mice, derived from Mus spretus, were found to be extremely
      resistant to infection with a mouse adapted influenza A virus. The resistance was
      strongly linked to distal chromosome 16, where the interferon-inducible Mx1 gene
      is located. This gene encodes for the Mx1 protein which stimulates innate
      immunity to Orthomyxoviruses. The Mx1 gene is defective in most inbred mouse
      strains, but PCR revealed that SPRET/Ei carries a functional allele. The Mx1
      proteins of M. spretus and A2G, the other major resistant strain derived from Mus
      musculus, share 95.7% identity. We were interested whether the sequence
      variations between the two Mx1 alleles have functional significance. To address
      this, we used congenic mouse strains containing the Mx1 gene from M. spretus or
      A2G in a C57BL/6 background. Using a highly pathogenic influenza virus strain, we
      found that the B6.spretus-Mx1 congenic mice were better protected against
      infection than the B6.A2G-Mx1 mice. This effect may be due to different Mx1
      induction levels, as was shown by RT-PCR and Western blot. We conclude that
      SPRET/Ei is a novel Mx1-positive inbred strain useful to study the biology of
      Mx1.

PMID- 18334302
TI  - Molecular packing in the feather keratin filament.
AB  - Avian feathers have a filament-matrix texture and X-ray diffraction studies show
      that the filament has a helical structure with four repeating units per turn.
      Each repeating unit consists of a pair of twisted beta-sheets related by a
      perpendicular diad, and the twist in the sheets is of opposite hand to that of
      the helix. Each sheet is believed to comprise a 32-residue segment of the feather
      keratin molecule, which contains around 100 residues, the remainder constituting
      the matrix. In the present contribution, the sequence of emu feather is mapped to
      the low-resolution model derived earlier from X-ray studies. This shows that the
      inner surface of the "beta-sandwich" is densely populated by hydrophobic residues
      and that the charged residues and cysteine residues lie on the outer surface. In
      addition, the inner residues in the repeating unit mesh neatly together in layers
      oriented perpendicular to the filament axis. Amino acid sequences from a range of
      avian and reptilian keratins were collected and a 32-residue segment
      corresponding to the filament framework could be identified in every case,
      supporting the notion that there is a common plan for the filament framework in
      all of these materials. The hairpin turns in the beta-sheet were also identified
      and shown to be unusually rich in proline residues and also of variable
      composition. Two variants of the mapping were found which have complimentary
      conformations of the hairpin turns and these are illustrated and discussed. Since
      feather keratin yields a fiber rather than a crystalline X-ray pattern refinement
      of the model is restricted to trial-and-error methods and the assumptions made in
      its derivation are critically examined and some possible modifications discussed.

PMID- 18334303
TI  - Evolution and phylogeny of the heterogeneous cytosolic SSU rRNA genes in the
      genus Plasmodium.
AB  - Unlike other eukaryotes, malaria parasites in the genus Plasmodium have
      structurally and functionally different paralogous copies of the cytosolic (cyto
      ) SSU rRNA (18S rRNA) gene that are expressed at different developmental stages.
      In P. falciparum, P. vivax, and P. berghei, A-type cyto-SSU rRNA is expressed in
      asexual stage, while S-type in sporozoite stage. A third type (O-type) has been
      described in P. vivax. It is expressed only in oocyst stage in the mosquito.
      Recently, it has been shown that the maintenance of heterogeneous cyto-SSU rRNAs
      in Plasmodium can be modeled as a birth-and-death process under strong purifying
      selection [Rooney, A.P., 2004. Mechanisms underlying the evolution and
      maintenance of functionally heterogeneous 18S rRNA genes in Apicomplexans. Mol.
      Biol. Evol. 21, 1704-1711]. In this study, we performed detailed phylogenetic
      analyses of Plasmodium cyto-SSU rRNAs with special emphasis on the evolution of
      multi-copy genes in simian Plasmodium species. We sequenced paralogous copies of
      the cyto-SSU rRNA genes from an African simian Plasmodium species, P. gonderi,
      and Asian simian Plasmodium species, P. fragile, P. coatneyi, P. inui, P.
      hylobati, P. fieldi, P. simiovale, and P. cynomolgi. Interestingly, all Asian
      simian Plasmodium species have a single S-type-like gene and several A-type-like
      genes. Alignment analysis demonstrated for the first time that an approximately
      50-residue insertion in the V7 variable region near the stem 43 is shared
      exclusively by the S-type-like sequences of the Asian simian Plasmodium species
      and the S- and O-type sequences of P. vivax. We comprehensively analyzed all cyto
      SSU rRNA sequences of the genus Plasmodium currently available in the database.
      Phylogenetic analyses of all publicly available cyto-SSU rRNA sequences for the
      genus Plasmodium clearly demonstrated that gene duplication events giving rise to
      A- and S-type-like sequences took place independently at least three times in the
      Plasmodium evolution, supporting the hypothesis that these genes evolve according
      to a birth-and-death model.

PMID- 18334304
TI  - Effects of pre-learning stress on memory for neutral, positive and negative
      words: Different roles of cortisol and autonomic arousal.
AB  - Stress can have enhancing or impairing effects on memory. Here, we addressed the
      effect of pre-learning stress on subsequent memory and asked whether neutral and
      emotionally valent information are differentially affected by specific stress
      components, autonomic arousal and stress-induced cortisol. Ninety-six healthy men
      and women underwent either a stressor (modified cold pressor test) or a control
      warm water exposure. During stress, participants showed comparable autonomic
      arousal (heart rate, blood pressure), while 60 percent showed an increase of
      cortisol (responders vs. 40 percent non-responders). Ten minutes after the cold
      pressor test neutral, positive and negative words were presented. Free recall was
      tested 1 and 24h later. Overall, positive and negative words were better recalled
      than neutral words. Stress enhanced the recall of neutral words independently of
      cortisol response. In contrast, the free recall of negative words was enhanced in
      cortisol responders in the 1-h but not 24-h test which might suggest different
      effects of cortisol on consolidation and reconsolidation processes. Recall for
      positive words was unaffected by stress-induced cortisol. To summarize, (i) pre
      learning stress can enhance memory for neutral words independently of cortisol
      and (ii) stress effects on memory for negative words appear to rely on stress
      induced cortisol elevations, the absence of this effect for positive words might
      be at least partly due to differences in arousal evoked by positive vs. negative
      words.

PMID- 18334305
TI  - Development of a MLST-biased SNP microarray for Candida albicans.
AB  - We have developed a single nucleotide polymorphism (SNP) detection microarray for
      the human pathogenic yeast, Candida albicans, consisting of synthetic
      oligonucleotides bound to microscope slides. The array consists of multiple
      replicates of 79 SNPs, derived from 19 discrete loci located on all eight
      chromosomes. These loci include seven genes consisting of 57 SNPs that comprise a
      multi-locus sequence typing (MLST) consensus scheme for the species. The
      remaining 22 SNPs are from 12 additional loci located at intervals on the
      remaining chromosomes. In order to include highly informative polymorphisms from
      the MLST set on the array we performed a linkage analysis of major genotypes
      between the two pairs of MLST-linked genes. In addition, we performed a matched
      set analysis for each SNP located within individual MLST loci. This analysis
      resulted in the reduction of informatively redundant mutations in the array for a
      large percentage of strains. We believe that a SNP array will be helpful in
      extending our knowledge of the epidemiology and genetics of C. albicans as a
      supplement to MLST typing.

PMID- 18334306
TI  - Movement-related cortical potentials in patients with Machado-Joseph disease.
AB  - OBJECTIVE: Movement-related cortical potentials (MRCP; nomenclature of MRCP
      components according to Shibasaki and Hallett (Shibasaki H, Hallett M. What is
      the Bereitschaftspotential? Clin Neurophysiol 2006;117:2341-56) were studied in
      patients with Machado-Joseph disease (MJD) to elucidate the pathophysiology of
      voluntary movement. METHODS: We studied nine genetically proven MJD patients and
      eight age-matched healthy subjects. Multi-channel electroencephalogram (EEG)
      recordings were obtained during self-paced fast extensions of the wrist. EEG
      epochs were time-locked to electromyography (EMG) onset or offset of the
      voluntary EMG burst and averaged. RESULTS: In the MJD patients, the early
      Bereitschaftspotential (early BP, -1500 to -500ms) was not affected but the late
      BP was reduced over the central midline area and contralaterally to the movement
      side. The amplitude of the fpMP, a post-movement MRCP component, was also
      reduced. In addition, the offset cortical potential in the first 500ms after EMG
      offset (Moff+500) was attenuated bilaterally over a wide cortical area.
      CONCLUSIONS: Findings suggest that cortical activations associated with the
      initiation and termination of a voluntary movement are impaired in MJD patients.
      SIGNIFICANCE: Abnormalities of pre- and post-movement MRCP components provide
      researchers with pathophysiological insight into voluntary motor dysfunction in
      MJD.

PMID- 18334307
TI  - Ameliorative missing value imputation for robust biological knowledge inference.
AB  - Gene expression data is widely used in various post genomic analyses. The data is
      often probed using microarrays due to their ability to simultaneously measure the
      expressions of thousands of genes. The expression data, however, contains
      significant numbers of missing values, which can impact on subsequent biological
      analysis. To minimize the impact of these missing values, several imputation
      algorithms including Collateral Missing Value Estimation (CMVE), Bayesian
      Principal Component Analysis (BPCA), Least Square Impute (LSImpute), Local Least
      Square Impute (LLSImpute), and K-Nearest Neighbour (KNN) have been proposed.
      These algorithms, however, exploit either only the global or local correlation
      structure of the data, which normally can lead to higher estimation errors. This
      paper presents an Ameliorative Missing Value Imputation (AMVI) technique which
      has ability to exploit global/local and positive/negative correlations in a given
      dataset by automatic selection of the optimal number of predictor genes k using a
      wrapper non-parametric method based on Monte Carlo simulations. The AMVI
      technique has CMVE strategy at its core because CMVE has demonstrated improved
      performance compared to both low variance methods like BPCA, LLSImpute, and high
      variance methods such as KNN and ZeroImpute, as CMVE exploits positive/negative
      correlations. The performance of AMVI is compared with CMVE, BPCA, LLSImpute, and
      KNN by randomly removing between 1% and 15% missing values in eight different
      ovarian, breast cancer and yeast datasets. Together with the standard NRMS error
      metric, the True Positive (TP) rate of the significant genes selection,
      biological significance of the selected genes and the statistical significance
      test results are presented to investigate the impact of missing values on
      subsequent biological analysis. The enhanced performance of AMVI was demonstrated
      by its lower NRMS error, improved TP rate, bio significance of the selected genes
      and statistical significance test results, when compared with the aforementioned
      imputation methods across all the datasets. The results show that AMVI adapted to
      the latent correlation structure of the data and proved to be an effective and
      robust approach compared with the trial and error methodology for selecting k.
      The results confirmed that AMVI can be successfully applied to accurately impute
      missing values prior to any microarray data analysis.

PMID- 18334308
TI  - Calorimetric study of extracellular tissue matrix degradation and instability
      after gamma irradiation.
AB  - Native extracellular tissue matrix (ECM) is increasingly used for tissue repair
      and regeneration. The kinetics of gamma irradiation damage on human dermis ECM
      was studied by differential scanning calorimetry (DSC). Dermis ECM was irradiated
      at a low-dose rate of 0.23 kGy h(-1) in order to study the progression of ECM
      damage as the gamma dose increased from 0 to 32 kGy. The study showed that the
      effect of gamma irradiation above 2 kGy was predominantly peptide chain scission.
      As the gamma dose increased, the stability of irradiated ECM decreased further,
      and multiple ECM domains of different stability were detected. Even a moderate
      gamma dose (7-12 kGy) could decrease the onset denaturation temperature of ECM to
      below body temperature. DSC analysis also showed partial and spontaneous protein
      denaturation in gamma-irradiated, rehydrated ECM at 37 degrees C. In vitro
      rehydration tests confirmed that a significant fraction of the irradiated ECM
      disintegrated into minute ECM fragments at 37 degrees C, although the irradiated
      ECM appeared to be normal at 4 degrees C and room temperature. DSC data were
      correlated well to effects of gamma irradiation on ECM microstructure, mechanical
      property and in vitro cell response reported earlier by us. A model was presented
      to describe the kinetics of gamma-irradiation-induced alterations of tissue ECM
      properties.

PMID- 18334309
TI  - Multifunctional implantable particles for skin tissue regeneration: preparation,
      characterization, in vitro and in vivo studies.
AB  - The transplantation of cell-polymer constructs has been developed as a novel
      approach to curing tissue defects. However, a number of methodological problems
      remain to be solved, including the loss of a proper cellular milieu, the
      relatively long period of culture time and the complexity of the application. The
      aim of the present article is to evaluate the feasibility of porous gelatin-based
      implantable particles as a novel strategy for delivery of cultured cells and
      bioactive molecules to correct dermal defects. For this purpose, implantable
      porous gelatin particles (100-230 microm) encapsulating proliferative growth
      factors were prepared and characterized, and their influence on fibroblasts was
      assessed. In vivo examinations were undertaken to observe guided dermal tissue
      regeneration after the transplantation of the implantable particles. Our results
      indicate the feasibility of transplanting multifunctional implantable particles
      as a culture substrate, as a protein transplantation vehicle or as a
      biodegradable implant for skin regeneration, thus giving an indication of the
      possible applications in tissue engineering.

PMID- 18334310
TI  - Spatial encoding using a code division technique for fast ultrasound imaging.
AB  - This paper describes a method for spatial encoding in synthetic transmit aperture
      ultrasound imaging. This allows several ultrasonic sources to be active
      simultaneously. The method is based on transmitting pseudorandom sequences to
      spatially encode the transmitters. The data can be decoded after only one
      transmission using the knowledge of the transmitted code sequences as opposed to
      other spatial encoding techniques, such as Hadamard or Golay encoding. This makes
      the method less sensitive to motion, and data can be acquired using fewer
      transmissions. The aim of this paper is to analyze the underlying theory and to
      test the feasibility in a physical system. The method has been evaluated in
      simulations using Field II in which the point-spread functions were simulated for
      different depths for a 7 MHz linear array transducer. A signal-to-noise ratio
      (SNR) simulation also was included in the study in which an improvement in SNR of
      approximately 1.5 dB was attained compared to the standard synthetic transmit
      aperture (STA) firing scheme. Considering the amount of energy transmitted, this
      value is low. A plausible explanation is given that is verified in simulation.
      The method also was tested in an experimental ultrasound scanner and compared to
      a synthetic transmit aperture ultrasound imaging scheme using a sinusoidal
      excitation. The performance of the proposed method was comparable to the
      reference with respect to axial and lateral resolution, but it displayed poorer
      contrast with sidelobe levels at approximately - 40 dB compared to the mainlobe.

PMID- 18334311
TI  - Displacement vector measurement using instantaneous ultrasound signal phase -
      multidimensional autocorrelation and doppler methods.
AB  - Two new methods of measuring a multidimensional displacement vector using an
      instantaneous ultrasound signal phase are described, i.e., the multidimensional
      autocorrelation method (MAM) and multidimensional Doppler method (MDM). A high
      measurement accuracy is achieved by combining either method with the lateral
      Gaussian envelope cosine modulation method (LGECMM) or multidirectional synthetic
      aperture method (MDSAM). Measurement accuracy is evaluated using simulated noisy
      echo data. Both methods yield accurate measurements comparable to that of our
      previously developed cross-spectrum phase gradient method (MCSPGM); however, they
      require less computational time (the order, MDM < MAM approximate, equals MCSPGM)
      and would provide realtime measurements. Moreover, comparisons of LGECMM and
      MDSAM performed by geometrical evaluations clarifies that LGECMM has potentials
      to yield more accurate measurements with less computational time. Both MAM and
      MDM can be applied to the measurement of tissue strain, blood flow, sonar data,
      and other target motions.

PMID- 18334312
TI  - Characterization of cell membrane response to ultrasound activated microbubbles.
AB  - Contrast agents for ultrasound imaging, composed of tiny gas microbubbles, have
      become a reality in clinical routine. They are extensively used in radiology for
      detection and characterization of various tumors and in cardiology for left
      ventricular opacification. Recent experimental studies showed that ultrasound
      waves in combination with contrast agent microbubbles increase transiently cell
      membrane permeability in a process known as sonoporation. This effect is thought
      to allow foreign molecules to enter the cell. In that context, we explored the
      cell membrane's responses to microbubbles' oscillations as the mechanism is not
      completely understood. Breast cancer cell line in combination with contrast
      microbubbles were used. Ultrasound was applied using a transducer of 1 MHz center
      frequency transmitting a 10-cycle burst of different acoustic pressures repeated
      every 100 mus. Patch-clamp technique in whole cell configuration was used to
      explore transmembrane ion exchange through the variations in membrane potential.
      To characterize the activated ion channels, the variations of the intracellular
      calcium (Ca(2+)) concentration were explored using a fluorescent marker. The
      results revealed that ultrasound stimulation induces a rapid hyperpolarization of
      cell membrane potential when the microbubble is in direct contact with the cell,
      but the potential returned to its initial value when ultrasound stimulation
      stopped. The change in cell membrane potential indicates the activation of
      specific ion channels and depends on the quality of microbubble adhesion to the
      cell membrane. Microbubbles were shown to induce a mechanical stretch activating
      BKca channels. Simultaneous Ca(2+) measurements indicate a slow and progressive
      Ca(2+) increase that is likely a consequence of BKca channels opening not a
      cause. These results demonstrate that microbubbles' oscillations under ultrasound
      activation entail modulation of cellular function and signaling by t- riggering
      the modulation of ionic transports through the cell membrane. Cells response to
      the mechanical stretch caused by gentle microbubble oscillations is characterized
      by the opening of BKca stretch channels and a Ca(2+) flux, which might
      potentially trigger other cellular responses responsible for membrane
      sonopermeabilization.

PMID- 18334313
TI  - Classification of simulated hyperplastic stages in the breast ducts based on
      ultrasound RF echo.
AB  - Visual inspection of ultrasound is diagnostically limited for characterizing
      breast tissue, in particular when it comes to visually detecting hyperplasia that
      forms in the ducts at its early formation (at submillimeter resolution) stages.
      It can, of course, be seen using biopsies. But this will not be done unless the
      areas have been flagged using noninvasive modalities. The aim of this paper is to
      draw to the attention of the medical community (albeit through simulations) that
      the continuous wavelet transform decomposition (CWTD) that was proven in vivo for
      tissue characterization before has the potential to flag out simulated
      hyperplasia data at submillimeter resolutions. And it might be an excellent
      candidate for detecting in vivo hyperplastic changes in the breast. To the best
      of our knowledge, this is the first attempt at studying the potential of
      detecting cell growth in breast ducts using ultrasound. The stochastic
      decomposition model (the CWTD) of the RF echo with its coherent and diffuse
      components, yields image parameters that correlate closely with the structural
      parameters of the (simulated) hyperplastic stages of the breast tissue. The
      discrimination power of the various parameters is studied under a host of
      conditions, such as varying resolution, depth, and coherent to diffuse energy
      ratio (CDR) values using a point-scatterer model simulator that mimics epithelium
      hyperplastic growth in the breast ducts. These are shown to be useful for
      detecting the various types of simulated hyperplastic data. Careful analysis
      shows that three parameters, in particular the number of coherent scatterers, the
      Rayleigh scattering degree, and the energy of the diffuse scatterers, are most
      sensitive to variations in the hyperplastic simulated data. And they show very
      high ability to discriminate between various stages of simulated hyperplasia,
      even in cases of low resolution and low CDR values. Using the area under the
      receiver operating characteristics (ROC) curve (A(z)) as the performance metric,
      values of A(z) > 0.942 are obtained when discriminating between stages for
      resolution <or= 0.4 mm, even for low CDR values. Then it drops below the 0.9
      range as the resolution exceeds the 0.4-mm range. A nonparametric segmentation
      method to extract ductal areas from breast scans is presented to be used as a pre
      step before classification of hyperplastic stages in breast ducts. This is a
      necessary step for segmenting the RF scan into ductal versus nonductal areas from
      breast scans. This is tested using breast tissue mimicking phantom data resulting
      values of A(z) > 0.948 for different duct densities.

PMID- 18334314
TI  - Broadband ultrasound attenuation in the calcaneal region: a comparative study of
      single-position versus scanning systems.
AB  - This work describes a system developed to measure the broadband ultrasound
      attenuation (BUA) in the calcaneal region. The patient's calcanei were inspected
      using a microcomputer-controlled X-Y axis displacement unit with two 500-kHz,
      central-frequency, ultrasound transducers. The transducers facing each other are
      submerged in a small water tank with a support for the patient's foot between
      them. The system allows data to be collected from a single position or by
      scanning the calcaneal region to obtain a BUA map. Tests were carried out on 201
      patients (110 using the single-position method, and 91 using the scanning
      method). The results were compared with those of densitometry tests performed
      using the dual energy X-ray absorptiometry (DEXA) technique (single position:
      r=0.50; P<0.0001; scanner: r=0.75; P<0.0001). It was concluded that the single
      position method is more susceptible to errors due to the difficulty in
      positioning the transducers relative to the calcaneus. The scanning method
      provides better results and can be used to screen patients before referring them
      for DEXA.

PMID- 18334315
TI  - Microcirculation volumetric flow assessment using high-resolution, contrast
      assisted images.
AB  - To improve the resolution of contrast-assisted imaging systems, we previously
      developed a 25-MHz microbubbles-destruction/replenishment imaging system with a
      spatial resolution of 160 X 160 microm. The goal of the present study was to
      propose a new approach for functionally evaluating the microvascular volumetric
      blood flow based on this high-frequency, ultrasound imaging system. The approach
      includes locating the perfusion area and estimating the blood flow velocity
      therein. Because the correlation changes between before and after microbubble
      destruction in two adjacent images, a correlated-based approach was introduced to
      detect the blood perfusion area. We also have derived a new sigmoid-based model
      for characterizing the microbubbles replenishment process. Two parameters derived
      from the sigmoid-based model - the rate constant and inflection time - were
      adopted to evaluate the blood flow velocity. This model was validated using both
      simulations and in vitro experiments for mean flow velocities ranging from 1 to
      10 mm/s, which showed that the model was in good agreement with simulated and
      measured microbubble-replenishment time-intensity curves. The results indicate
      that the actual flow velocity is highly correlated with the estimates of the rate
      constant and the reciprocal of the inflection time. B-mode imaging experiments
      for mean flow velocities ranging from 0.4 to 2.1 mm/s were used to assess the
      volumetric flow in the microcirculation. The results indicated the high
      correlation between the actual volumetric flow rate and the product of the
      estimated perfusion area and rate constant, and the reciprocal of the inflection
      time. We also found that the boundary of the microbubble destruction volume
      significantly affected estimations of the flow velocity. The perfusion area can
      be located, and the corresponding flow velocity can be estimated simultaneously
      in a one-stage, microbubble-destruction/replenishment process, which makes the
      assessment of the volumetric bloo- d flow in the microcirculation feasible using
      a real-time, high-frequency ultrasound system.

PMID- 18334316
TI  - A nonlinear propagation model-based phase calibration technique for membrane
      hydrophones.
AB  - A technique for the phase calibration of membrane hydrophones in the frequency
      range up to 80 MHz is described. This is achieved by comparing measurements and
      numerical simulation of a nonlinearly distorted test field. The field prediction
      is obtained using a finite-difference model that solves the nonlinear Khokhlov
      Zabolotskaya-Kuznetsov (KZK) equation in the frequency domain. The measurements
      are made in the far field of a 3.5 MHz focusing circular transducer in which it
      is demonstrated that, for the high drive level used, spatial averaging effects
      due to the hydrophone's finite-receive area are negligible. The method provides a
      phase calibration of the hydrophone under test without the need for a device
      serving as a phase response reference, but it requires prior knowledge of the
      amplitude sensitivity at the fundamental frequency. The technique is demonstrated
      using a 50-microm thick bilaminar membrane hydrophone, for which the results
      obtained show functional agreement with predictions of a hydrophone response
      model. Further validation of the results is obtained by application of the
      response to the measurement of the high amplitude waveforms generated by a modern
      biomedical ultrasonic imaging system. It is demonstrated that full deconvolution
      of the calculated complex frequency response of a nonideal hydrophone results in
      physically realistic measurements of the transmitted waveforms.

PMID- 18334317
TI  - Phase-based ultrasonic deformation estimation.
AB  - Deformation estimation is the foundation of emerging techniques for imaging the
      mechanical properties of soft tissues. We present theoretical analysis and
      experimental results from an investigation of phase-based ultrasonic deformation
      estimators. Numerous phase-based algorithm variants were tested quantitatively on
      simulated RF data from uniform scatterer fields, subject to a range of uniform
      strain deformations. Particular attention is paid to a new algorithm, weighted
      phase separation, the performance of which is demonstrated in application to in
      vivo freehand strain imaging. Good results support the theory that underlies the
      new algorithm, and more generally highlight the factors that should be considered
      in the design of high performance deformation estimators for practical
      applications. For context, note that this represents progress with an algorithm
      class that is suitable for real-time applications, yet has already been shown
      quantitatively to offer greater accuracy over a wide range of scanning conditions
      than adaptive companding methods based on correlation coefficient or sum of
      absolute differences.

PMID- 18334318
TI  - A study on the reconstruction of moderate contrast targets using the distorted
      born iterative method.
AB  - Previous tomographic methods using ultrasound for reconstructing sound speed and
      attenuation images suffered from convergence issues for targets with moderate
      speed of sound contrast. Convergence problems can be overcome by the use of the
      multiple frequency, distorted Born iterative method (DBIM). The implementation of
      DBIM for measurement configurations in which receiver positions are fixed was
      studied, and a novel regularization scheme was developed. The regularization
      parameter needed to stabilize the inversion process initially was found through
      the Rayleigh quotient iteration, then relaxed according to the relative residual
      error between the measured and estimated scattered fields. The DBIM was
      successfully stabilized for both full and partial receiver angular coverage
      without a significant loss in spatial resolution. The effects of variable density
      in the reconstructions were briefly explored through simulations. The ability to
      reconstruct targets with moderate contrast was validated through experimental
      measurements. Speed of sound profiles for balloons filled with saline in a
      background of water were reconstructed using multiple frequency DBIM techniques.
      The mean squared error for speed of sound reconstructions of the balloon phantoms
      with 16.4% sound speed contrast was 1.1%.

PMID- 18334319
TI  - Prediction of surface temperature rise of ultrasonic diagnostic array
      transducers.
AB  - Temperature rise at the surface of an ultrasound transducer used for diagnostic
      imaging is an important factor in patient safety and regulatory compliance. This
      paper presents a semianalytical model that is derived from first principles of
      heat transfer and is simple enough to be implemented in a commercial ultrasound
      scanner for real-time forecasting of transducer surface temperature. For modeling
      purposes, one-dimensional array transducers radiating into still air are
      considered. Promising experimental verification data are shown and practical
      implementation benefits of the model for thermal design and management of
      ultrasonic array transducers are discussed. In particular, the reduction in the
      amount of thermal characterization data required, compared to empirical models,
      shows promise.

PMID- 18334320
TI  - Self-heating study of bulk acoustic wave resonators under high RF power.
AB  - The present work first provides an experimental technique to study self-heating
      of bulk acoustic wave (BAW) resonators under high RF power in the gigahertz
      range. This study is specially focused on film bulk acoustic wave resonators and
      solidly mounted resonators processed onto silicon wafers and designed for
      wireless systems. Precisely, the reflection coefficient of a one-port device is
      measured while up to several watts are applied and power leads to electrical
      drifts of impedances. In the following, we describe how absorbed power can be
      determined from the incident one in real time. Therefore, an infrared camera held
      over the radio frequency micro electromechanical system (RF-MEMS) surface with an
      exceptional spatial resolution reaching up to 2 microm/pixels gives accurate
      temperature mapping of resonators after emissivity correction. From theoretical
      point of view, accurate three-dimensional (3-D) structures for finite-element
      modeling analyses are carried out to know the best materials and architectures to
      use for enhancing power handling. In both experimental and theoretical
      investigations, comparison is made between film bulk acoustic wave resonators and
      solidly mounted resonators. Thus, the trend in term of material, architecture,
      and size of device for power application such as in transmission path of a
      transceiver is clearly identified.

PMID- 18334321
TI  - Nonlinear interface between the piezoelectric harvesting structure and the
      modulating circuit of an energy harvester with a real storage battery.
AB  - This paper studies the performance of an energy harvester with a piezoelectric
      bimorph (PB) and a real electrochemical battery (ECB), both are connected as an
      integrated system through a rectified dc-dc converter (DDC). A vibrating PB can
      scavenge energy from the operating environment by the electromechanical coupling.
      A DDC can effectively match the optimal output voltage of the harvesting
      structure to the battery voltage. To raise the output power density of PB, a
      synchronized switch harvesting inductor (SSHI) is used in parallel with the
      harvesting structure to reverse the voltage through charge transfer between the
      output electrodes at the transition moments from closed-to open-circuit. Voltage
      reversal results in earlier arrival of rectifier conduction because the output
      voltage phases of any two adjacent closed-circuit states are just opposite each
      other. In principle, a PB is with a smaller, flexural stiffness under closed
      circuit condition than under open-circuit condition. Thus, the PB subjected to
      longer closed-circuit condition will be easier to be accelerated. A larger
      flexural velocity makes the PB to deflect with larger amplitude, which implies
      that more mechanical energy will be converted into an electric one. Nonlinear
      interface between the vibrating PB and the modulating circuit is analyzed in
      detail, and the effects of SSHI and DDC on the charging efficiency of the storage
      battery are researched numerically. It was found that the introduction of a DDC
      in the modulating circuit and an SSHI in the harvesting structure can raise the
      charging efficiency by several times.

PMID- 18334322
TI  - Methodology for developing a high-precision ultrasound flow meter and fluid
      velocity profile reconstruction.
AB  - This article reports the methodology used to develop a high-precision ultrasound
      transit time flow meter dedicated to liquid hydrocarbons. This kind of flow meter
      is designed for custody transfer applications requiring accuracy better than
      0.15% of reading. We focus here on certain specific points to achieve this
      accuracy. The transit time method needs to estimate accurately the time delay
      between signals received by a pair of transducers. In this study, we review
      different ways of estimating this time delay. We also propose a specific
      configuration of the flow meter paths. In particular, this configuration
      compensates for the swirl phenomenon, which has a significant impact on the
      accuracy of the flow meter. We also propose a theoretical parametric profile to
      reconstruct the fluid velocity profile in order to perform in situ diagnosis of
      the flow. The parameters of the model are estimated from the measurements of the
      flow meter. Simulations and experimental results showed that this method provides
      characterization of the flow in disturbed and undisturbed flow conditions.

PMID- 18334323
TI  - Numerical implementation of matching pursuit for the analysis of complex
      ultrasonic signals.
AB  - Matching pursuit has typically been applied to ultrasonic signal analysis for the
      purpose of identifying or estimating discrete echoes. In this paper, a specific
      numerical implementation of matching pursuit designed for ultrasonic signal
      decomposition is proposed, consisting of the selection of a coarse set of basis
      functions, the search method for finding the best matching basis function, and
      interpolation of the basis function parameters to achieve high resolution. In
      addition, the use of matching pursuit is applied to the analysis of complex
      ultrasonic signals by interpreting the matching basis functions as characteristic
      wavelets. Changes in parameters of these wavelets are related to changes in the
      structure. The efficiency of the numerical implementation method is evaluated,
      and the capability of the feature extraction method for complex ultrasonic
      signals is demonstrated on experimental data from an aluminum plate in the
      context of structural health monitoring.

PMID- 18334324
TI  - An adaptive recurrent radial basis function network tracking controller for a two
      dimensional piezo-positioning stage.
AB  - An adaptive recurrent radial basis function network (ARRBFN) tracking controller
      for a two-dimensional piezo-positioning stage is proposed in this study. First, a
      mathematical model that represents the dynamics of the two-dimensional piezo
      positioning stage is proposed. In this model, a hysteresis friction force that
      describes the hysteresis behavior of one-dimensional motion is used; and a
      nonconstant stiffness with the cross-coupling dynamic due to the effect of
      bending of a lever mechanism in x and y axes also is included. Then, according to
      the proposed mathematical model, an ARRBFN tracking controller is proposed. In
      the proposed ARRBFN control system, a recurrent radial basis function network
      (RRBFN) with accurate approximation capability is used to approximate an unknown
      dynamic function. The adaptive learning algorithms that can learn the parameters
      of the RRBFN on line are derived using Lyapunov stability theorem. Moreover, a
      robust compensator is proposed to confront the uncertainties, including
      approximation error, optimal parameter vectors, higher-order terms in Taylor
      series. To relax the requirement of the value of the lumped uncertainty in the
      robust compensator, an adaptive law is investigated to estimate the lumped
      uncertainty. Using the proposed control scheme, the position tracking performance
      is substantially improved and the robustness to uncertainties, including
      hysteresis friction force and cross-coupling stiffness, can be obtained as well.
      The tracking performance and the robustness to external load of the proposed
      ARRBFN control system are illustrated by some experimental results.

PMID- 18334325
TI  - Temperature-stable double SAW resonators.
AB  - The temperature stability of SAW resonators on quartz can be enhanced by means of
      double resonators. The turnover temperatures of the double resonators'
      components, called single resonators, are positioned above and below room
      temperature. As a consequence, the temperature coefficients of frequency of the
      1st order (TCF1) have opposite signs at room temperature, leading to the
      vanishing TCF1 of the double resonators. Frequently, different turnover
      temperatures are adjusted by different propagation directions on an ST cut of
      quartz. An overview of known and new methods for compensating the temperature
      coefficient of frequency of the 2nd order (TCF2) of two-port and one-port SAW
      double resonators is given. A concept by means of which temperature-stable
      circuits of single resonators are found is described. Two types of temperature
      stable double resonators found by applying that concept are treated in detail: 1)
      a two-port resonator composed of two cascaded two-port resonators and a coupling
      inductance, and 2) a one-port resonator comprising a series connection of one
      port resonators with an inductance in parallel with each single resonator. The
      substrates are 35.5 degrees rotY cuts of quartz. In both cases, the shift of
      resonance frequency within the temperature range from -30 degrees C to 70 degrees
      C is smaller than 20 ppm.

PMID- 18334326
TI  - Z-path SAW RFID tag.
AB  - Surface acoustic wave (SAW) radio-frequency identification (RFID) tags are soon
      expected to be produced in very high volumes. The size and cost of a SAW RFID tag
      will be key parameters for many applications. Therefore, it is of primary
      importance to reduce the chip size. In this work, we describe the design
      principles of a 2.4-GHz SAW RFID tag that is significantly smaller than earlier
      reported tags. We also present simulated and experimental results. The coded
      signal should arrive at the reader with a certain delay (typically about 1
      micros), i.e., after the reception of environmental echoes. If the tag uses a
      bidirectional interdigital transducer (IDT), space for the initial delay is
      needed on both sides of the IDT. In this work, we replace the bidirectional IDT
      by a unidirectional one. This halves the space required by the initial delay
      because all the code reflectors must now be placed on the same side of the IDT.
      We reduce tag size even further by using a Z-path geometry in which the same
      space in x-direction is used for both the initial delay and the code reflectors.
      Chip length is thus determined only by the space required by the code reflectors.

PMID- 18334327
TI  - Lead-free piezoelectric ceramic transducer in the donor-doped K1/2Na1/2NbO3 solid
      solution system.
AB  - Lead-based piezoelectric ceramics are suitable materials for noninvasive
      applications of ultrasound in medicine. However, the embedded therapeutic and
      diagnostic procedures require the use of lead-free piezoelectric materials as
      active elements in transducers. With this goal in mind, we investigated the
      substitution of Ba(2+) cations in a lead-free piezoelectric system of
      K(1/2)Na(1/2)NbO(3)-LiTaO(3)-LiSbO(3) (KNN-LT-LS) with perovskite structure. The
      Ba(2+) was added to the system as an A-site dopant in the range of 0-2 mol% in
      increments of 0.5 mol%. The addition of Ba(2+) improved the piezoelectric charge
      coefficient, d(33), and longitudinal coupling coefficient, k(33). The composition
      with 1 mol% Ba2+ had 36% and 58% higher d(33) and k(33), respectively, than the
      undoped composition. It appeared that the addition of Ba(2+) induced "soft"
      characteristics in this lead-free piezoelectric system. This was verified by the
      increase of remnant polarization along with the decline of coercive field. The
      Ba(2+) behaved as a grain growth inhibitor and caused a drastic reduction in
      polarization level (approximately 60%) when the grain size became smaller than
      approximately 1.5 microm. Incorporation of Ba(2+) up to 1.5 mol% increased the
      bulk resistivity of the KNN-LT-LS system and then reduced it drastically at
      higher dopant concentrations. The electron-hole compensation model fit well with
      the results obtained in this study and verified the A-site substitution of donor
      doped barium. KNN-LT-LS ceramics with 0 mol% and 1 mol% Ba(2+) were used to
      fabricate single-element ultrasonic transducers resonating at 5.5 MHz. The -6 dB
      fractional bandwidth and -20 dB pulse length of the probe made of doped ceramic
      were 50% and 1.68 micros, respectively. This indicated that this system could be
      considered as a candidate for invasive and/or embedded medical ultrasound
      applications.

PMID- 18334328
TI  - Estimation of the surface normal velocity of high frequency ultrasound
      transducers.
AB  - This paper is concerned with the characterization of the true locally resolved
      surface normal velocity of an assumed piston-type ultrasonic transducer. Instead
      of involving a very complicated direct pointwise measurement of the velocity
      distribution, an inverse problem is solved which yields a spatially discretized
      weighting vector for the surface normal velocity of the transducer. The study
      deals with a spherically focused high frequency transducer, which is driven in
      pulse-echo mode. As a means of posing the inverse problem, the active transducer
      surface is divided into annuli of equal surface so that for each annulus the
      spatial impulse response can be calculated. An acrylic glass plate acts as a
      simple structured target. The resulting ill-posed nonlinear inverse problem is
      solved with an iterative regularized Gauss-Newton algorithm. The solution of the
      inverse problem yields an estimated weight for the surface normal velocity for
      each annulus. Experimental results for a thin copper wire target are compared to
      simulation results for both uniform and estimated surface normal velocities.

PMID- 18334329
TI  - Synthetic axial acquisition-full resolution, low-cost C-scan ultrasonic imaging.
AB  - The synthetic axial acquisition (SAA) approach presented here is designed to
      produce C-scan images using low-cost, low bandwidth, front end electronics. We
      exploit plane wave transmission and shallow C-scan imaging of non-moving, or
      slowly moving, tissue regions. Between each transmit/receive cycle, the receive
      sampling trigger is offset by one sampling interval so that over a sequence of
      acquisitions a sufficiently long data record is synthesized to enable a high
      quality approximation to conventional delay and sum beamforming. FIELD II
      simulations were performed to model the next generation of our sonic window C
      scan imaging system using a 5 MHz center frequency, 50% bandwidth, and a 60x60
      fully sampled two-dimensional (2- D) array with a 0.3-mm element pitch. These
      simulations, which include analysis of the impact of target motion both parallel
      and perpendicular to the acoustic beam, indicate that SAA is robust with respect
      to target motion no faster than 10 mm/s. The impact of electronic noise on SAA
      also is considered.

PMID- 18334330
TI  - High-frame rate, full-view myocardial elastography with automated contour
      tracking in murine left ventricles in vivo.
AB  - Myocardial elastography is a novel method for noninvasively assessing regional
      myocardial function, with the advantages of high resolution and high precision.
      The purpose in this paper was to isolate the left ventricle from other structures
      for better displacement and strain visualization. Using a high-resolution (30
      MHz) ultrasound system and a retrospective electrocardiogram (ECG)-gating
      technique, an extremely high frame rate (up to 8 kHz) was previously shown
      achievable for full-view (12-mm times 12-mm) myocardial elastography in the
      murine left ventricle. In vivo experiments were performed in anesthetized normal
      and infarcted mice [one day after left anterior descending (LAD) coronary artery
      ligation]. Radio frequency (RF) signals of the left ventricle (LV) in the long
      axis view and the associated ECG were simultaneously acquired, with the ECG
      allowing gating of the RF signals. Incremental axial displacement of the
      myocardium was estimated using a one-dimensional (1-D) cross-correlation
      function. The cumulative displacement and strain then were calculated from the
      incremental displacement. In this paper, after manual selection of 40-50 points
      along the endo-and epicardial borders in the first frame of the cine-loop,
      myocardial contour was automatically tracked across the entire LV throughout a
      full cardiac cycle, which correctly determined the region of interest (ROI) for
      better interpretation. The cine-loop of the cumulative displacement and strain in
      one cardiac cycle, in both the normal and infarcted cases, showed that motion and
      deformation in the infarcted myocardium were significantly reduced, and that the
      infarcted region underwent thinning, rather than thickening, during systole. High
      precision of the displacement estimation, due to high frequency (30 MHz) and high
      frame rate (up to 8 kHz) available with this system, allowed for automated
      tracking of a manually-initialized myocardial contour over an entire cardiac
      cycle. High frame rate, full-view myocardial elastography with automated contour
      tracking could provide regional strain information of the LV throughout an entire
      cardiac cycle, and characterize normal as well as detect abnormal myocardial
      function, such as an infarction. The method of automated contour tracking can
      further enhance the capability of the elastographic technique with minimal user
      intervention while providing accurate functional information for the detection of
      disease throughout the entire cardiac cycle.

PMID- 18334331
TI  - Improved contrast ultrasound with tissue harmonic minimizing pulse.
AB  - We have computed predistorted pulses that minimize tissue harmonics to < -25 dB
      compared to fundamental over a 4-cm depth in the focal region using a Hankel
      transform-based algorithm. The results indicate their potential in achieving
      patient independent improvement in contrast with microbubbles using wideband
      ultrasonic transducers at high mechanical indices.

PMID- 18334332
TI  - A new method for estimation of elastic properties of sintered iron powder
      compacts from ultrasonic longitudinal velocity.
AB  - A new methodology has been proposed for estimation of elastic moduli of iron
      powder compacts solely based on longitudinal ultrasonic velocity. New
      correlations have been semianalytically derived between the elastic moduli and
      the longitudinal ultrasonic velocity. The moduli estimated on the basis of the
      suggested methodology agreed reasonably well with data reported for iron powder
      compacts in the literature. The proposed method can be a potent tool for quick
      and accurate, nondestructive estimation of elastic properties for porous
      materials through ultrasonic measurements.

PMID- 18334333
TI  - Phononic crystals based on LiNbO3 realized using domain inversion by electron
      beam irradiation.
AB  - We report in this paper about the realization of domain inversion in z-cut
      lithium niobate by electron beam irradiation in order to perform phononic
      crystals. The fabrication of these phononic crystals on z-cut LiNbO3, which is,
      in our case, a periodic repetition of voids and LiNbO3, was achieved by domain
      inversion followed by wet etching, taking advantage of the large difference in
      etching rate between z+ and z- faces. A pertinent choice of irradiation
      conditions such as accelerating voltage, beam current, and charge density was
      determined and optimized. Two-dimensional structures at the micrometer scale were
      then realized on z-cut LiNbO3. We demonstrate the achievement of hexagons with
      diameters between 2 microm and 18 microm, with a very important depth close to 30
      microm, which depends on the etching time and the hole size. The obtained
      structures, which exhibit a filling fraction varying from 1% to 64%, were
      characterized before etching by polarizing microscope to visualize the inverted
      domains. After HF etching, scanning electron microscopy was used to observe the
      obtained phononic structures. Taking into account the obtained filling fraction
      values and the size of created hexagons, the frequency band gap of these
      structures is expected at a range of 200 to 350 MHz. As expected in this
      frequency range, we have proven experimentally the existence of the phononic band
      gap on z-cut LiNbO3 by combination of a realized phononic crystal with a surface
      acoustic wave (SAW) device.

PMID- 18334334
TI  - Energy harvesting based on FE-FE transition in ferroelectric single crystals.
AB  - The pyroelectric properties of Pb(Zn(1/3)Nb(2/3))(0955)Ti(0.045)O(3) single
      crystals versus an electric field have been studied for energy harvesting in this
      paper. Two thermodynamic cycles (Stirling and Ericsson) were used for this
      purpose. By applying an electric field, a FE-FE transition was induced, abruptly
      increasing the polarization. This transition minimized the supplied energy and
      improved the harvested energy. By discharging the single crystal at a higher
      temperature, a gain of 1100% was obtained with the Stirling cycle at 1 kV/mm
      (gain is defined as harvested energy divided by supplied energy). The study
      revealed that Stirling cycles are more interesting for low electric fields. Based
      on experimental results, simulations were carried out to estimate energy
      harvesting in high electric fields to evaluate the performances of thin samples
      (single crystals or oriented thin films). At high electric fields, both cycles
      gave almost the same energy harvesting, but Ericsson cycles were more appropriate
      to control the voltage on the sample. The simulation led to a harvested energy of
      500 mJ/g for an applied electric field equal to 50 kV/mm. The efficiency with
      respect to Carnot was raised 20%.

PMID- 18334335
TI  - Influence of space-charge on hysteresis loop characteristics of ferroelectric
      thin films.
AB  - Hysteresis loops of Pb(Zr, Ti)O3 (PZT) thin films obtained by using a Sawyer
      Tower (ST) circuit are affected by many factors. This paper investigated the
      influence of space charge on the hysteresis loop of thin-film ferroelectrics,
      based on the model that polarization consists of two parts: linear and switching
      polarization. It is found that the space charge affects both the shape and offset
      of the ideal hysteresis loop. Further investigation shows that the practical
      hysteresis loop has a close relationship with the equivalent ST circuit
      parameters: the leakage resistance of the FE film, the equivalent input impedance
      of the measurement equipment, the signal source, and other similar parameters.
      The normally assumed symmetric hysteresis loop without any offset is obtained
      with an ST circuit when the output becomes stable. The hysteresis loop obtained
      at the initial stage of applied signal depends on the initial status of the FE
      film, and remnant polarization causes an initial offset that gradually
      disappears.

PMID- 18334336
TI  - A variational principle for the equations of viscopiezoelectricity.
AB  - The three-dimensional equations of linear viscopiezoelectricity and an
      accompanying electromechanical energy theorem are deduced, by the
      quasielectrostatic approximation, from the equations of viscoelectromagnetism and
      a generalized Poynting's theorem, respectively. For a viscopiezoelectric solid of
      volume V and bounding surface S, the internal energy, kinetic energy, and
      electric enthalpy densities as well as the variation of work done over S and the
      variation of energy dissipation in V are defined. A variational principle in
      terms of the defined functions is presented. It is shown that, from the
      principle, the equations of viscopiezoelectricity in V and the natural boundary
      conditions on S are obtained.

PMID- 18334337
TI  - Regularization of tissue shear modulus reconstruction using strain variance.
AB  - An effective setting method (that is, a method using the variances of strain
      tensor component measurements) is described for the properly spatially varied
      regularization parameters for our shear modulus reconstruction. At each position,
      the respective strain variances can be experimentally evaluated using plural
      field measurements or single field measurement, for example, when using all
      crosscorrelation- based methods, by using the Ziv-Zakai Lower Bound (ZZLB). The
      demonstrated regularization by the single field measurement using the cross
      spectrum phase gradient method (MCSPGM) in experiments confirms that the use of
      the axial strain variance estimated by the echo signal-to-noise ratio and
      correlations (the combined SNRc) effectively stabilizes the 1-D reconstruction on
      an agar phantom and a human in vivo liver carcinoma during interstitial microwave
      thermal treatment. The regularization yields a spatially uniform stability in
      reconstruction.

PMID- 18334338
TI  - Element shape design of 2-D CMUT arrays for reducing grating lobes.
AB  - Fully populated two-dimensional (2-D) arrays are needed to produce high quality
      ultrasonic volumetric images for real-time applications, but they present many
      challenges for their physical realization because of the large number of
      elements. In fact, lambda/2 and lambda minimum spacing between elements is
      required, respectively, for pyramidal and rectilinear scanning in order to avoid
      unwanted grating lobes (GLs). However, in past years, capacitive micromachined
      ultrasonic transducer (CMUT) technology has made possible the production of
      arrays with large flexibility in element shape and size. In this paper, this
      property is analyzed, and a new element shape, based on the concept of spatial
      interpenetration of adjacent elements, is proposed in order to design fully
      populated 2-D CMUT arrays with a low number of elements, whose beam
      characteristics are valid for volumetric imaging. Through the use of simulations,
      it is demonstrated that arrays with pitch larger than lambda (up to 3lambda) used
      for rectilinear scanning, have notably lower GLs than the equivalent standard
      arrays designed according to the classical squared element shape. As consequence,
      the proposed geometry has the advantage of reducing the number of elements (up to
      a factor of 9) and of enlarging the element size, implying an increase of the SNR
      relative to the single element. When beam steering is required, arrays can be
      designed with pitch equal to lambda, reducing the number of elements by a factor
      of 4 if the maximum steering angle is limited to +/-15 degrees .

PMID- 18334339
TI  - Elasticity reconstruction from displacement and confidence measures of a multi
      compressed ultrasound RF sequence.
AB  - Ultrasound elasticity imaging shows promise as a new way for early detection of
      cancers by assessing the elastic characteristics of soft tissue. So far the
      commonly used approach involves solving the so-called inverse elasticity problem
      of recovering elastic parameters from displacement measurements. We propose a
      finite-elementbased nonlinear scheme to estimate the elasticity distribution of
      soft tissue from multi-compressed ultrasound radio frequency (RF) data. An
      experimental ultrasound workstation has been developed to acquire multi
      compressed data. A composite probe was employed as the compression plate. The
      contact forces and torques were acquired at the same time as imaging. Axial
      displacements under different static loads are estimated from the RF data before
      and after deformation using a cross-correlation technique. The confidence of
      displacement estimates is employed as a weighting factor in solving the objective
      function describing the inverse elasticity reconstruction problem. A novel
      splitand- merge strategy is employed over the image sequence in which strain
      images are used to provide a priori knowledge of the relative stiffness
      distribution of the tissue to constrain the inverse problem solution. The
      experimental study has allowed us to investigate the performance of our approach
      in the controlled environment of simulated and phantom data. For a simulated
      single inclusion model with 5% axial displacement estimation error, the L2-error
      between the target and the reconstructed Young's modulus was found to be about
      1%. In vivo validation of the proposed method has been carried out and some
      preliminary results are presented.

PMID- 18334340
TI  - Integration of 2D CMUT arrays with front-end electronics for volumetric
      ultrasound imaging.
AB  - For three-dimensional (3D) ultrasound imaging, connecting elements of a two
      dimensional (2D) transducer array to the imaging system's front-end electronics
      is a challenge because of the large number of array elements and the small
      element size. To compactly connect the transducer array with electronics, we flip
      chip bond a 2D 16 x 16-element capacitive micromachined ultrasonic transducer
      (CMUT) array to a custom-designed integrated circuit (IC). Through-wafer
      interconnects are used to connect the CMUT elements on the top side of the array
      with flip-chip bond pads on the back side. The IC provides a 25-V pulser and a
      transimpedance preamplifier to each element of the array. For each of three
      characterized devices, the element yield is excellent (99 to 100% of the elements
      are functional). Center frequencies range from 2.6 MHz to 5.1 MHz. For pulse echo
      operation, the average - 6-dB fractional bandwidth is as high as 125%. Transmit
      pressures normalized to the face of the transducer are as high as 339 kPa and
      input-referred receiver noise is typically 1.2 to 2.1 mPa/pHz. The flip-chip
      bonded devices were used to acquire 3D synthetic aperture images of a wire-target
      phantom. Combining the transducer array and IC, as shown in this paper, allows
      for better utilization of large arrays, improves receive sensitivity, and may
      lead to new imaging techniques that depend on transducer arrays that are closely
      coupled to IC electronics.

PMID- 18334341
TI  - Narrowband shear wave generation by a Finite-Amplitude radiation force: The
      fundamental component.
AB  - A highly localized source of low-frequency shear waves can be created by the
      modulated radiation force resulting from two intersecting quasi-continuous-wave
      ultrasound beams of slightly different frequencies. In contrast to most other
      radiation force-based methods, these shear waves can be narrowband. Consequently,
      different frequency-dependent effects will not significantly affect their
      spectrum as they propagate within a viscoelastic medium, thereby enabling the
      viscoelastic shear properties of the medium to be determined at any given
      modulation frequency. This can be achieved by tracking the shear wave phase delay
      and change in amplitude over a specific distance. In this paper we explore the
      properties of short duration (dynamic) low-frequency shear wave propagation and
      study how the shear displacement field depends on the excitation conditions. Our
      investigations make use of the approximate Green's functions for viscoelastic
      media, and the evolution of such waves is studied in the spatiotemporal domain
      from a theoretical perspective. Although nonlinearities are included in our
      confocal source model, just the properties of the fundamental shear component are
      examined in this paper. We examine how the shear wave propagation is affected by
      the shear viscosity, the coupling wave, the spatial distribution of the force,
      the shear speed, and the duration of the modulated wave. A method is proposed for
      estimating the shear viscosity of a viscoelastic medium. In addition, it is shown
      how the Voigt model paremeters can be extracted from the frequency-dependent
      speed and attenuation.

PMID- 18334342
TI  - A harmonic cancellation technique for an ultrasound transducer excited by a
      switched-mode power converter.
AB  - The aim of this study is to evaluate the feasibility of using harmonic
      cancellation for a therapeutic ultrasound transducer excited by a switched-mode
      power converter without an additional output filter. A switching waveform without
      the third harmonic was created by cascading two switched-mode power inverter
      modules at which their output waveforms were pi/3 phase shifted from each other.
      A PSPICE simulation model for the power converter output stage was developed. The
      simulated results were in good agreement with the measurement. The waveform and
      harmonic contents of the acoustic pressure generated by a 1-MHz, self-focused
      piezoelectric transducer with and without harmonic cancellation have been
      evaluated. Measured results indicated that the acoustic third harmonicto-
      fundamental ratio at the focus was small (-48 dB) with harmonic cancellation,
      compared to that without harmonic cancellation (-20 dB). The measured acoustic
      levels of the fifth harmonic for both cases with and without harmonic
      cancellation also were small (-46 dB) compared to the fundamental. This study
      shows that it is viable to drive a piezoelectric ultrasound transducer using a
      switched-mode power converter without the requirement of an additional output
      filter in many high-intensity focused ultrasound (HIFU) applications.

PMID- 18334343
TI  - Viscoelastic property measurement in thin tissue constructs using ultrasound.
AB  - We present a dual-element concave ultrasound transducer system for generating and
      tracking of localized tissue displacements in thin tissue constructs on rigid
      substrates. The system is comprised of a highly focused PZT-4 5-MHz acoustic
      radiation force (ARF) transducer and a confocal 25-MHz polyvinylidene fluoride
      imaging transducer. This allows for the generation of measurable displacements in
      tissue samples on rigid substrates with thickness values down to 500 microm.
      Impulse-like and longer duration sine-modulated ARF pulses are possible with
      intermittent M-mode data acquisition for displacement tracking. The operations of
      the ARF and imaging transducers are strictly synchronized using an integrated
      system for arbitrary waveform generation and data capture with a shared timebase.
      This allows for virtually jitter-free pulse-echo data well suited for correlation
      based speckle tracking. With this technique we could faithfully capture the
      entire dynamics of the tissue axial deformation at pulse-repetition frequency
      values up to 10 kHz. Spatio-temporal maps of tissue displacements in response to
      a variety of modulated ARF beams were produced in tissue-mimicking elastography
      phantoms on rigid substrates. The frequency response was measured for phantoms
      with different modulus and thickness values. The frequency response exhibited
      resonant behavior with the resonance frequency being inversely proportional to
      the sample thickness. This resonant behavior can be used in obtaining high
      contrast imaging using magnitude and phase response to sinusoidally modulated ARF
      beams. Furthermore, a second order forced harmonic oscillator (FHO) model was
      shown to capture this resonant behavior. Based on the FHO model, we used the
      extended Kalman filter (EKF) for tracking the apparent modulus and viscosity of
      samples subjected to dc and sinusoidally modulated ARF. The results show that the
      stiffness (apparent modulus) term in the FHO is largely time-invariant and can be
      estimated robustly using the EKF. On the other hand, the damping (apparent
      viscosity) is time varying. These findings were confirmed by comparing the
      magnitude response of the FHO (with parameters obtained using the EKF) with the
      measured ones for different thin tissue constructs.

PMID- 18334344
TI  - The effect of phase cancellation on estimates of broadband ultrasound attenuation
      and backscatter coefficient in human calcaneus in vitro.
AB  - Broadband ultrasound attenuation (BUA) is a clinically proven indicator of
      osteoporotic fracture risk. BUA measurements are typically performed in
      throughtransmission with single-element phase sensitive (PS) receivers and
      therefore can be compromised by phase cancellation artifact. Phase-insensitive
      (PI) receivers suppress phase cancellation artifact. To study the effect of phase
      cancellation on BUA measurements, through-transmission measurements were
      performed on 16 human calcaneus samples in vitro using a two-dimensional receiver
      array that enabled PS and PI BUA estimation. The means plus or minus standard
      deviations for BUA measurements were 22.1 +/- 15.8 dB/MHz (PS) and 17.6 +/- 7.2
      dB/MHz (PI), suggesting that, on the average, approximately 20% of PS BUA values
      in vitro can be attributed to phase cancellation artifact. Therefore, although
      cortical plates are often regarded as the primary source of phase cancellation
      artifact, the heterogeneity of cancellous bone in the calcaneal interior may also
      be a significant source. Backscatter coefficient estimates in human calcaneus
      that are based on PS attenuation compensation overestimate 1) average magnitude
      of backscatter coefficient at 500 kHz by a factor of about 1.6 +/- 0.3 and 2)
      average exponent (n) of frequency dependence by about 0.34 +/- 0.12 (where
      backscatter coefficient is fit to a power law form proportional to frequency to
      the nth power).

PMID- 18334345
TI  - Ultrasonic scattering by a fluid cylinder of elliptic cross section, including
      viscous effects.
AB  - This paper analyzes acoustic scattering by a viscous compressible fluid cylinder
      of elliptic cross section submerged in an unbounded viscous nonheat-conducting
      compressible fluid medium. The classical method of eigenfunction expansion along
      with the appropriate wave field expansions and the pertinent boundary conditions
      are used to develop a solution in the form of infinite series involving Mathieu
      and modified Mathieu functions of complex arguments. The complications arising
      due to the nonorthogonality of angular Mathieu functions corresponding to
      distinct wave numbers in addition to the problems associated with the appearance
      of additional angular-dependent terms in the boundary conditions are all avoided
      in an elegant manner by expansion of the angular Mathieu functions in terms of
      transcendental functions and subsequent integration, leading to a linear set of
      independent equations in terms of the unknown scattering coefficients. A
      multiprecision code was developed for computing the Mathieu functions of complex
      argument in terms of complex Fourier coefficients that are themselves calculated
      by numerically solving appropriate sets of eigen-systems. The numerical results
      point to the imperative influence of fluid viscosity in notable reduction of
      pressure amplitudes at intermediate and high frequencies. They also reveal the
      central role of the cross sectional ellipticity in conjunction with the angle of
      incidence in altering the pressure directivities. Limiting cases are considered,
      and fair agreements with well-known solutions are obtained.

PMID- 18334346
TI  - Beam profile measurements using light refractive tomography.
AB  - A method for reconstructing the sound pressure profile from interferometer
      measurements using computed tomography is presented. In accordance with the term
      light diffraction tomography, in short we want to call the method light
      refractive tomography, because it is based on the sound pressure-induced
      refractive index change along the laser beam. We compare three tomographic
      reconstruction methods applicable to axisymmetric beam profiles, namely, the
      filtered back-projection, the Hankel Fourier method, and the onion peeling
      method, the latter based on Nestor and Olsens algorithm. Results are compared to
      hydrophone measurements. The performance of the tomographic algorithms are
      reflected by general considerations on the reconstruction of noise signals.

PMID- 18334347
TI  - DeltaE effect for polycrystalline ferromagnetic rods.
AB  - We performed experimental and computational studies of the acoustic transfer
      power coefficient for carbon steel cylindric bars placed in axial magnetic field.
      By experiment, the transmission coefficients of velocity were measured for
      ferromagnetic bars during the first magnetization curve below saturation. Using
      the magnetic and magnetostriction material measurements we obtained the profile
      of the magnetostriction along the distance for a ferromagnetic cylindrical rod
      placed in a magnetic field parallel with its axis. The data were compared with
      numerical results obtained by computer simulation, under the assumption of
      spatial dependent acoustic impedance and phase velocity, leading to the
      conclusion that the Young modulus is affected by the magnetoelastic interaction
      according to a linear decrease.

PMID- 18334348
TI  - Modeling for temperature compensation and temperature characterizations of BAW
      resonators at GHz frequencies.
AB  - This paper deals with the temperature dependence of electrical and physical
      features of various kinds of solidly mounted resonators (SMR). The presented bulk
      acoustic wave (BAW) devices are designed for the 2 GHz application. The
      temperature coefficient of frequency (TCF) is determined from measurements well
      above the temperature range defined for wireless telecommunication system
      specifications. Therefore, evolution of electromechanical coupling factors and
      quality factors at resonance and antiresonance are also monitored. Results of
      characterizations show the trend for a subsequent theoretical temperature
      compensation study by using analytical modeling. To improve accuracy of modeling,
      an attempt to extract temperature dependence of dielectric permittivity
      epsilon(33) and piezoelectric coefficient e(33) is made. Finally, a well-known
      analytical model is modified to take into account the temperature dependence of
      length, density, stiffness coefficient, dielectric permittivity, and
      piezoelectric coefficient. Modeling highlights the need to deposit a material
      with positive temperature coefficient of stiffness on the top electrode.
      Realistic thickness of such a layer is determined. At the same time, it is
      necessary to adjust piezoelectric and electrode thin film thicknesses for
      simultaneously keeping a constant antiresonance frequency, reaching a zero
      temperature coefficient of frequency for antiresonance, and minimizing the
      decrease in the coupling factor because of the mass-loading deposition.

PMID- 18334349
TI  - Calculations of Lamb wave band gaps and dispersions for piezoelectric phononic
      plates using mindlin's theory-based plane wave expansion method.
AB  - Based on Mindlin's piezoelectric plate theory and the plane wave expansion
      method, a formulation is proposed to study the frequency band gaps and dispersion
      relations of the lower-order Lamb waves in two-dimensional piezoelectric phononic
      plates. The method is applied to analyze the phononic plates composed of solid
      solid and airsolid constituents with square and triangular lattices,
      respectively. Factors that influence the opening and width of the complete Lamb
      wave gaps are identified and discussed. For solid/solid phononic plates, it is
      suggested that the filling material be chosen with larger mass density, proper
      stiffness, and weak anisotropic factor embedded in a soft matrix in order to
      obtain wider complete band gaps of the lower-order Lamb waves. By comparing to
      the calculated results without considering the piezoelectricity, the influences
      of piezoelectric effect on Lamb waves are analyzed as well. On the other hand,
      for air/solid phononic plates, a background material itself with proper
      anisotropy and a high filling fraction of air may favor the opening of the
      complete Lamb wave gaps.

PMID- 18334350
TI  - GHz frequency ZnO/Si SAW device.
AB  - The demand for high-frequency low-loss filters generates intensive research on
      innovative wave guide solutions. In this work, a GHz SAW device based on a ZnO/Si
      structure was fabricated using classical UV photolithography. The thickness of
      the piezoelectric thin film was optimized and a specific interdigital transducer
      structure was used to generate third and fifth harmonic guided waves at 2.5 GHz
      and 3.5 GHz, respectively, with an aluminum strip larger than 1 micrometer.
      Different modes have been measured and theoretically identified thanks to an
      advanced finite-element/boundary-elementbased model. Good agreement is found
      between theory and experiments. The high-frequency modes have been fully
      characterized, allowing for accurate design of SAW devices exploiting such modes.

PMID- 18334352
TI  - FEM-Based determination of real and complex elastic, dielectric, and
      piezoelectric moduli in piezoceramic materials.
AB  - We propose an enhanced iterative scheme for the precise reconstruction of
      piezoelectric material parameters from electric impedance and mechanical
      displacement measurements. It is based on finite-element simulations of the full
      three-dimensional piezoelectric equations, combined with an inexact Newton or
      nonlinear Landweber iterative inversion scheme. We apply our method to two
      piezoelectric materials and test its performance. For the first material, the
      manufacturer provides a full data set; for the second one, no material data set
      is available. For both cases, our inverse scheme, using electric impedance
      measurements as input data, performs well.

PMID- 18334351
TI  - Ultrasonic imaging using a computed point spread function.
AB  - An explicit point spread function (PSF) evaluator in the frequency domain is
      described for an ultrasonic transducer operating in the pulse-echo mode. The PSF
      evaluator employs the patch element model for transducer field determination and
      scattered field assessment from a small but finite "point" reflector. The PSF for
      a planar transducer in a medium has been evaluated in the near and the far field.
      The computed PSFs were used to deconvolve and restore surface images, obtained
      experimentally, of a single hole and a five-hole cluster in an Al calibration
      block. A calibration plot is arrived at for estimating, without the need for
      deconvolution, the actual diameters of circular reflectors from apparent
      diameters obtained experimentally for a single-medium imaging configuration. The
      PSF, when the transducer and the point reflector are in two media separated by a
      planar interface, was evaluated in the near and far field. The computed PSFs were
      used to deconvolve and restore subsurface images, obtained experimentally, of
      flat bottom holes (FBHs) in an Al calibration block. We show that the PSF, in the
      presence of a planar interface, can be obtained from a single-medium PSF model
      using an effective single-medium path length concept. The PSFs and modulation
      transfer functions (MTFs) are evaluated for spherical focused and annular
      transducers and compared with those for the planar transducer. We identify
      imaging distances to get better-resolved images when using planar, spherical
      focused, and annular transducers.

PMID- 18334353
TI  - Full Tensorial characterization of PZN-12%PT single crystal by resonant
      ultrasound spectroscopy.
AB  - An experimental setup based on the electrical excitation of a piezoelectric
      sample is proposed for resonant ultrasound spectroscopy measurements. The
      detection of the mechanical vibrations is performed by means of a laser
      interferometer. At the same time, the free vibrations of piezoelectric
      parallelepipeds of tetragonal and hexagonal symmetries are modeled taking into
      account the effect of the sample metalization. The paper presents the full
      elastic, piezoelectric and dielectric tensors of two PMN-34.5%PT ceramic and PZN
      12%PT single crystal cubes.

PMID- 18334354
TI  - Suitability of surface acoustic wave oscillators fabricated using low temperature
      grown AlN films on GaN/sapphire as UV sensors.
AB  - Epitaxial AlN films were prepared on GaN/sapphire using a helicon sputtering
      system at the low temperature of 300 degrees C. Surface acoustic wave (SAW)
      devices fabricated on AlN/GaN/sapphire exhibited superior characteristics
      compared with those made on GaN/sapphire. An oscillator using an
      AlN/GaN/sapphirebased SAW device is presented. The oscillation frequency
      decreased when the device was illuminated by ultraviolet (UV) radiation, and the
      downshift of the oscillation frequency increased with the illuminating UV power
      density. The results showed that the AlN/GaN/sapphire-layered structure SAW
      oscillators are suitable for visible blind UV detection and opened up the
      feasibility of developing remote UV sensors for different ranges of wavelengths
      on the III-nitrides.

PMID- 18334355
TI  - Narrow electrodes on YZ-LiNbOO3 as an alternative to etched grooves for
      dispersive delay lines.
AB  - Narrow, open-circuited aluminum electrodes can provide controllable, weak
      reflectivity necessary for many applications such as surface acoustic wave (SAW)
      tags and dispersive delay lines (DDLs). We show, using finiteand boundary element
      method (FEM-BEM) based simulations and experiments, that a reflectivity of 0.3%
      per wavelength can be achieved easily and controlled by varying the electrode
      width.

PMID- 18334356
TI  - A freestanding oscillator for resonant-ultrasound microscopy.
AB  - Resonant-ultrasound microscopy with a freestanding rod oscillator has been
      developed for mapping a material's elastic properties in a localized surface
      region, for the purpose of evaluating elastic stiffness through the resonance
      frequency of the oscillator contacting the specimen by its tip. A stronger
      biasing static magnetic field makes the ferritic steel oscillator plumb without
      any other mechanical support except tip-sample contact. For a noncontacting
      acoustical coupling, the longitudinal vibration of the oscillator is excited and
      detected with a surrounding solenoid coil by the magnetostrictive effect. This
      freestanding configuration realizes only a mechanical "point" contact between the
      oscillator and the sample surface, which yields accurate measurement of the local
      elastic stiffness. As an illustrated example, the new microscopy method is
      applied to an SCS- 6 SiCf/Ti-6Al-4V composite to visualize its elastic-stiffness
      distribution.

PMID- 18334357
TI  - Lee plate equations for electroded quartz crystal plates with the consideration
      of electrode density and stiffness.
AB  - Lee plate equations for high-frequency vibrations of piezoelectric plates have
      been established and improved over the last decades with the sole objective of
      obtaining the accurate prediction of frequency and mode shapes to aid crystal
      resonator design. The latest improvement includes extra terms related to
      derivatives of the flexural displacement to adjust the accuracy and consider
      electrodes for practical applications. As part of the efforts to make the
      equations applicable for resonator design with the improved frequency accuracy
      and consideration of electrodes, we derived Lee plate equations for electroded
      plates by changing the integration limits in the dimension reduction procedure to
      signify the dominant role of the crystal plate. By modifying the density terms in
      plate equations to include the contribution of both electrode stiffness and
      density, the accuracy of the thickness-shear vibration frequency of electroded
      plates is improved for commonly used electrode materials.

PMID- 18334358
TI  - Chirp-coded excitation imaging with a high-frequency ultrasound annular array.
AB  - High-frequency ultrasound (HFU, > 15 MHz) is an effective means of obtaining fine
      resolution images of biological tissues for applications such as opthalmologic,
      dermatologic, and small animal imaging. HFU has two inherent drawbacks. First,
      HFU images have a limited depth of field (DOF) because of the short wavelength
      and the low fixed F-number of conventional HFU transducers. Second, HFU can be
      used to image only a few millimeters deep into a tissue because attenuation
      increases with frequency. In this study, a five-element annular array was used in
      conjunction with a synthetic-focusing algorithm to extend the DOF. The annular
      array had an aperture of 10 mm, a focal length of 31 mm, and a center frequency
      of 17 MHz. To increase penetration depth, 8-micros, chirp-coded signals were
      designed, input into an arbitrary waveform generator, and used to excite each
      array element. After data acquisition, the received signals were linearly
      filtered to restore axial resolution and increase the SNR. To compare the
      chirpcoded imaging method with conventional impulse imaging in terms of
      resolution, a 25-microm diameter wire was scanned and the -6-dB axial and lateral
      resolutions were computed at depths ranging from 20.5 to 40.5 mm. The results
      demonstrated that chirp-coded excitation did not degrade axial or lateral
      resolution. A tissue-mimicking phantom containing 10-microm glass beads was
      scanned, and backscattered signals were analyzed to evaluate SNR and penetration
      depth. Finally, ex vivo ophthalmic images were formed and chirpcoded images
      showed features that were not visible in conventional impulse images.

PMID- 18334359
TI  - Selecting useful groups of features in a connectionist framework.
AB  - Suppose for a given classification or function approximation (FA) problem data
      are collected using l sensors. From the output of the ith sensor, ni features are
      extracted, thereby generating p = sigma li = 1 ni features, so for the task we
      have X subset Rp as input data along with their corresponding outputs or class
      labels Y subset Rc. Here, we propose two connectionist schemes that can
      simultaneously select the useful sensors and learn the relation between X and Y.
      One scheme is based on the radial basis function (RBF) network and the other uses
      the multilayered perceptron (MLP) network. Both schemes are shown to possess the
      universal approximation property. Simulations show that the methods can detect
      the bad/derogatory groups of features online and can eliminate the effect of
      these bad features while doing the FA or classification task.

PMID- 18334360
TI  - Global exponential stability of bidirectional associative memory neural networks
      with time delays.
AB  - In this paper, we consider delayed bidirectional associative memory (BAM) neural
      networks (NNs) with Lipschitz continuous activation functions. By applying
      Young's inequality and Hoelder's inequality techniques together with the
      properties of monotonic continuous functions, global exponential stability
      criteria are established for BAM NNs with time delays. This is done through the
      use of a new Lyapunov functional and an M-matrix. The results obtained in this
      paper extend and improve previous results.

PMID- 18334361
TI  - A class of complex ICA algorithms based on the kurtosis cost function.
AB  - In this paper, we introduce a novel way of performing real-valued optimization in
      the complex domain. This framework enables a direct complex optimization
      technique when the cost function satisfies the Brandwood's independent
      analyticity condition. In particular, this technique has been used to derive
      three algorithms, namely, kurtosis maximization using gradient update (KM-G),
      kurtosis maximization using fixed-point update (KM-F), and kurtosis maximization
      using Newton update (KM-N), to perform the complex independent component analysis
      (ICA) based on the maximization of the complex kurtosis cost function. The
      derivation and related analysis of the three algorithms are performed in the
      complex domain without using any complex-real mapping for differentiation and
      optimization. A general complex Newton rule is also derived for developing the KM
      N algorithm. The real conjugate gradient algorithm is extended to the complex
      domain similar to the derivation of complex Newton rule. The simulation results
      indicate that the fixed-point version (KM-F) and gradient version (KM-G) are
      superior to other similar algorithms when the sources include both circular and
      noncircular distributions and the dimension is relatively high.

PMID- 18334362
TI  - A hybrid technique for blind separation of non-gaussian and time-correlated
      sources using a multicomponent approach.
AB  - Blind inversion of a linear and instantaneous mixture of source signals is a
      problem often encountered in many signal processing applications. Efficient
      fastICA (EFICA) offers an asymptotically optimal solution to this problem when
      all of the sources obey a generalized Gaussian distribution, at most one of them
      is Gaussian, and each is independent and identically distributed (i.i.d.) in
      time. Likewise, weights-adjusted second-order blind identification (WASOBI) is
      asymptotically optimal when all the sources are Gaussian and can be modeled as
      autoregressive (AR) processes with distinct spectra. Nevertheless, real-life
      mixtures are likely to contain both Gaussian AR and non-Gaussian i.i.d. sources,
      rendering WASOBI and EFICA severely suboptimal. In this paper, we propose a novel
      scheme for combining the strengths of EFICA and WASOBI in order to deal with such
      hybrid mixtures. Simulations show that our approach outperforms competing
      algorithms designed for separating similar mixtures.

PMID- 18334363
TI  - Performing feature selection with multilayer perceptrons.
AB  - An experimental study on two decision issues for wrapper feature selection (FS)
      with multilayer perceptrons and the sequential backward selection (SBS) procedure
      is presented. The decision issues studied are the stopping criterion and the
      network retraining before computing the saliency. Experimental results indicate
      that the increase in the computational cost associated with retraining the
      network with every feature temporarily removed before computing the saliency is
      rewarded with a significant performance improvement. Despite being quite
      intuitive, this idea has been hardly used in practice. A somehow nonintuitive
      conclusion can be drawn by looking at the stopping criterion, suggesting that
      forcing overtraining may be as useful as early stopping. A significant
      improvement in the overall results with respect to learning with the whole set of
      variables is observed.

PMID- 18334364
TI  - Automatic cluster detection in Kohonen's SOM.
AB  - Kohonen's self-organizing map (SOM) is a popular neural network architecture for
      solving problems in the field of explorative data analysis, clustering, and data
      visualization. One of the major drawbacks of the SOM algorithm is the difficulty
      for nonexpert users to interpret the information contained in a trained SOM. In
      this paper, this problem is addressed by introducing an enhanced version of the
      Clusot algorithm. This algorithm consists of two main steps: 1) the computation
      of the Clusot surface utilizing the information contained in a trained SOM and 2)
      the automatic detection of clusters in this surface. In the Clusot surface,
      clusters present in the underlying SOM are indicated by the local maxima of the
      surface. For SOMs with 2-D topology, the Clusot surface can, therefore, be
      considered as a convenient visualization technique. Yet, the presented approach
      is not restricted to a certain type of 2-D SOM topology and it is also applicable
      for SOMs having an n-dimensional grid topology.

PMID- 18334365
TI  - Self-organizing radial basis function network for real-time approximation of
      continuous-time dynamical systems.
AB  - Real-time approximators for continuous-time dynamical systems with many inputs
      are presented. These approximators employ a novel self-organizing radial basis
      function (RBF) network, which varies its structure dynamically to keep the
      prescribed approximation accuracy. The RBFs can be added or removed online in
      order to achieve the appropriate network complexity for the real-time
      approximation of the dynamical systems and to maintain the overall computational
      efficiency. The performance of this variable structure RBF network approximator
      with both Gaussian RBF (GRBF) and raised-cosine RBF (RCRBF) is analyzed. The
      compact support of RCRBF enables faster training and easier output evaluation of
      the network than that of the network with GRBF. The proposed real-time self
      organizing RBF network approximator is then employed to approximate both linear
      and nonlinear dynamical systems to illustrate the effectiveness of our proposed
      approximation scheme, especially for higher order dynamical systems. The uniform
      ultimate boundedness of the approximation error is proved using the second method
      of Lyapunov.

PMID- 18334366
TI  - Two-microphone separation of speech mixtures.
AB  - Separation of speech mixtures, often referred to as the cocktail party problem,
      has been studied for decades. In many source separation tasks, the separation
      method is limited by the assumption of at least as many sensors as sources.
      Further, many methods require that the number of signals within the recorded
      mixtures be known in advance. In many real-world applications, these limitations
      are too restrictive. We propose a novel method for underdetermined blind source
      separation using an instantaneous mixing model which assumes closely spaced
      microphones. Two source separation techniques have been combined, independent
      component analysis (ICA) and binary time - frequency (T-F) masking. By estimating
      binary masks from the outputs of an ICA algorithm, it is possible in an iterative
      way to extract basis speech signals from a convolutive mixture. The basis signals
      are afterwards improved by grouping similar signals. Using two microphones, we
      can separate, in principle, an arbitrary number of mixed speech signals. We show
      separation results for mixtures with as many as seven speech signals under
      instantaneous conditions. We also show that the proposed method is applicable to
      segregate speech signals under reverberant conditions, and we compare our
      proposed method to another state-of-the-art algorithm. The number of source
      signals is not assumed to be known in advance and it is possible to maintain the
      extracted signals as stereo signals.

PMID- 18334367
TI  - A fault-tolerant regularizer for RBF networks.
AB  - In classical training methods for node open fault, we need to consider many
      potential faulty networks. When the multinode fault situation is considered, the
      space of potential faulty networks is very large. Hence, the objective function
      and the corresponding learning algorithm would be computationally complicated.
      This paper uses the Kullback-Leibler divergence to define an objective function
      for improving the fault tolerance of radial basis function (RBF) networks. With
      the assumption that there is a Gaussian distributed noise term in the output
      data, a regularizer in the objective function is identified. Finally, the
      corresponding learning algorithm is developed. In our approach, the objective
      function and the learning algorithm are computationally simple. Compared with
      some conventional approaches, including weight-decay-based regularizers, our
      approach has a better fault-tolerant ability. Besides, our empirical study shows
      that our approach can improve the generalization ability of a fault-free RBF
      network.

PMID- 18334368
TI  - An expectation-maximization method for spatio-temporal blind source separation
      using an AR-MOG source model.
AB  - In this paper, we develop a maximum-likelihood (ML) spatio-temporal blind source
      separation (BSS) algorithm, where the temporal dependencies are explained by
      assuming that each source is an autoregressive (AR) process and the distribution
      of the associated independent identically distributed (i.i.d.) innovations
      process is described using a mixture of Gaussians. Unlike most ML methods, the
      proposed algorithm takes into account both spatial and temporal information,
      optimization is performed using the expectation-maximization (EM) method, the
      source model is adapted to maximize the likelihood, and the update equations have
      a simple, analytical form. The proposed method, which we refer to as
      autoregressive mixture of Gaussians (AR-MOG), outperforms nine other methods for
      artificial mixtures of real audio. We also show results for using AR-MOG to
      extract the fetal cardiac signal from real magnetocardiographic (MCG) data.

PMID- 18334369
TI  - Exponential stability of discrete-time genetic regulatory networks with delays.
AB  - Discrete-time versions of the continuous-time genetic regulatory networks (GRNs)
      with SUM regulatory functions are formulated and studied in this letter.
      Sufficient conditions are derived to ensure the global exponential stability of
      the discrete-time GRNs with delays. An illustrative example is given to
      demonstrate the effectiveness of the obtained results.

PMID- 18334370
TI  - Wavelet basis function neural networks for sequential learning.
AB  - In this letter, we develop the wavelet basis function neural networks (WBFNNs).
      It is analogous to radial basis function neural networks (RBFNNs) and to wavelet
      neural networks (WNNs). In WBFNNs, both the scaling function and the wavelet
      function of a multiresolution approximation (MRA) are adopted as the basis for
      approximating functions. A sequential learning algorithm for WBFNNs is presented
      and compared to the sequential learning algorithm of RBFNNs. Experimental results
      show that WBFNNs have better generalization property and require shorter training
      time than RBFNNs.

PMID- 18334371
TI  - An improved algebraic criterion for global exponential stability of recurrent
      neural networks with time-varying delays.
AB  - This brief paper presents an M-matrix-based algebraic criterion for the global
      exponential stability of a class of recurrent neural networks with decreasing
      time-varying delays. The criterion improves some previous criteria based on M
      matrix and is easy to be verified with the connection weights of the recurrent
      neural networks with decreasing time-varying delays. In addition, the rate of
      exponential convergence can be estimated via a simple computation based on the
      criterion herein.

PMID- 18334372
TI  - A new criterion of delay-dependent asymptotic stability for Hopfield neural
      networks with time delay.
AB  - In this brief, the problem of global asymptotic stability for delayed Hopfield
      neural networks (HNNs) is investigated. A new criterion of asymptotic stability
      is derived by introducing a new kind of Lyapunov-Krasovskii functional and is
      formulated in terms of a linear matrix inequality (LMI), which can be readily
      solved via standard software. This new criterion based on a delay fractioning
      approach proves to be much less conservative and the conservatism could be
      notably reduced by thinning the delay fractioning. An example is provided to show
      the effectiveness and the advantage of the proposed result.

PMID- 18334373
TI  - Energy function and energy evolution on neuronal populations.
AB  - Based on the principle of energy coding, an energy function of a variety of
      electric potentials of a neural population in cerebral cortex is formulated. The
      energy function is used to describe the energy evolution of the neuronal
      population with time and the coupled relationship between neurons at the
      subthreshold and the suprathreshold states. The Hamiltonian motion equation with
      the membrane potential is obtained from the neuroelectrophysiological data
      contaminated by Gaussian white noise. The results of this research show that the
      mean membrane potential is the exact solution of the motion equation of the
      membrane potential developed in a previously published paper. It also shows that
      the Hamiltonian energy function derived in this brief is not only correct but
      also effective. Particularly, based on the principle of energy coding, an
      interesting finding is that in some subsets of neurons, firing action potentials
      at the suprathreshold and some others simultaneously perform activities at the
      subthreshold level in neural ensembles. Notably, this kind of coupling has not
      been found in other models of biological neural networks.

PMID- 18334374
TI  - On a neural approximator to ODEs.
AB  - The object of this brief is to present and analyze the training of a single-layer
      neural network in order to solve ordinary differential equations (ODEs).
      Properties of the approximator are derived and some examples of its application
      are shown.

PMID- 18334376
TI  - Modeling the forces of cutting with scissors.
AB  - Modeling forces applied to scissors during cutting of biological materials is
      useful for surgical simulation. Previous approaches to haptic display of scissor
      cutting are based on recording and replaying measured data. This paper presents
      an analytical model based on the concepts of contact mechanics and fracture
      mechanics to calculate forces applied to scissors during cutting of a slab of
      material. The model considers the process of cutting as a sequence of deformation
      and fracture phases. During deformation phases, forces applied to the scissors
      are calculated from a torque-angle response model synthesized from measurement
      data multiplied by a ratio that depends on the position of the cutting crack edge
      and the curve of the blades. Using the principle of conservation of energy, the
      forces of fracture are related to the fracture toughness of the material and the
      geometry of the blades of the scissors. The forces applied to scissors generally
      include high-frequency fluctuations. We show that the analytical model accurately
      predicts the average applied force. The cutting model is computationally
      efficient, so it can be used for real-time computations such as haptic rendering.
      Experimental results from cutting samples of paper, plastic, cloth, and chicken
      skin confirm the model, and the model is rendered in a haptic virtual
      environment.

PMID- 18334377
TI  - An improved PID switching control strategy for type 1 diabetes.
AB  - In order for an "artificial pancreas" to become a reality for ambulatory use, a
      practical closed-loop control strategy must be developed and validated. In this
      paper, an improved PID control strategy for blood glucose control is proposed and
      critically evaluated in silico using a physiologic model of Hovorka et al. [1].
      The key features of the proposed control strategy are: 1) a switching strategy
      for initiating PID control after a meal and insulin bolus; 2) a novel time
      varying setpoint trajectory; 3) noise and derivative filters to reduce
      sensitivity to sensor noise; and 4) a practical controller tuning strategy.
      Simulation results demonstrate that proposed control strategy compares favorably
      to alternatives for realistic conditions that include meal challenges, incorrect
      carbohydrate meal estimates, changes in insulin sensitivity, and measurement
      noise.

PMID- 18334378
TI  - Understanding perceptual boundaries in laparoscopic surgery.
AB  - Human perceptual capabilities related to the laparoscopic interaction paradigm
      are not well known. Its study is important for the design of virtual reality
      simulators, and for the specification of augmented reality applications that
      overcome current limitations and provide a supersensing to the surgeon. As part
      of this work, this article addresses the study of laparoscopic pulling forces.
      Two definitions are proposed to focalize the problem: the perceptual fidelity
      boundary, limit of human perceptual capabilities, and the Utile fidelity
      boundary, that encapsulates the perceived aspects actually used by surgeons to
      guide an operation. The study is then aimed to define the perceptual fidelity
      boundary of laparoscopic pulling forces. This is approached with an experimental
      design in which surgeons assess the resistance against pulling of four different
      tissues, which are characterized with both in vivo interaction forces and ex vivo
      tissue biomechanical properties. A logarithmic law of tissue consistency
      perception is found comparing subjective valorizations with objective parameters.
      A model of this perception is developed identifying what the main parameters are:
      the grade of fixation of the organ, the tissue stiffness, the amount of tissue
      bitten, and the organ mass being pulled. These results are a clear requirement
      analysis for the force feedback algorithm of a virtual reality laparoscopic
      simulator. Finally, some discussion is raised about the suitability of augmented
      reality applications around this surgical gesture.

PMID- 18334379
TI  - A model-predictive hypnosis control system under total intravenous anesthesia.
AB  - In ambulatory surgery, anesthetic drugs must be administered at a suitable rate
      to prevent adverse reactions after discharge from the hospital. To realize more
      appropriate anesthesia, we have developed a hypnosis control system, which
      administers propofol as an anesthetic drug to regulate the bispectral index
      (BIS), an electroencephalography (EEG)-derived index reflecting the hypnosis of a
      patient. This system consists of three functions: 1) a feedback controller using
      a model-predictive control method, which can adequately accommodate the effects
      of time delays; 2) a parameter estimation function of individual differences; and
      3) a risk control function for preventing undesirable states such as drug
      overinfusion or intraoperative arousal. With the approval of the ethics committee
      of our institute, 79 clinical trials took place since July 2002. The results show
      that our system can reduce the total amount of propofol infusion and maintain the
      BIS more accurately than anesthesiologist's manual adjustment.

PMID- 18334380
TI  - A fully automatic CAD-CTC system based on curvature analysis for standard and low
      dose CT data.
AB  - Computed tomography colonography (CTC) is a rapidly evolving noninvasive medical
      investigation that is viewed by radiologists as a potential screening technique
      for the detection of colorectal polyps. Due to the technical advances in CT
      system design, the volume of data required to be processed by radiologists has
      increased significantly, and as a consequence the manual analysis of this
      information has become an increasingly time consuming process whose results can
      be affected by inter- and intrauser variability. The aim of this paper is to
      detail the implementation of a fully integrated CAD-CTC system that is able to
      robustly identify the clinically significant polyps in the CT data. The CAD-CTC
      system described in this paper is a multistage implementation whose main system
      components are: 1) automatic colon segmentation; 2) candidate surface extraction;
      3) feature extraction; and 4) classification. Our CAD-CTC system performs at 100%
      sensitivity for polyps larger than 10 mm, 92% sensitivity for polyps in the range
      5 to 10 mm, and 57.14% sensitivity for polyps smaller than 5 mm with an average
      of 3.38 false positives per dataset. The developed system has been evaluated on
      synthetic and real patient CT data acquired with standard and low-dose radiation
      levels.

PMID- 18334381
TI  - Tracking the time-varying cortical connectivity patterns by adaptive multivariate
      estimators.
AB  - The directed transfer function (DTF) and the partial directed coherence (PDC) are
      frequency-domain estimators that are able to describe interactions between
      cortical areas in terms of the concept of Granger causality. However, the
      classical estimation of these methods is based on the multivariate autoregressive
      modelling (MVAR) of time series, which requires the stationarity of the signals.
      In this way, transient pathways of information transfer remains hidden. The
      objective of this study is to test a time-varying multivariate method for the
      estimation of rapidly changing connectivity relationships between cortical areas
      of the human brain, based on DTF/PDC and on the use of adaptive MVAR modelling
      (AMVAR) and to apply it to a set of real high resolution EEG data. This approach
      will allow the observation of rapidly changing influences between the cortical
      areas during the execution of a task. The simulation results indicated that time
      varying DTF and PDC are able to estimate correctly the imposed connectivity
      patterns under reasonable operative conditions of signal-to-noise ratio (SNR) ad
      number of trials. An SNR of five and a number of trials of at least 20 provide a
      good accuracy in the estimation. After testing the method by the simulation
      study, we provide an application to the cortical estimations obtained from high
      resolution EEG data recorded from a group of healthy subject during a combined
      foot-lips movement and present the time-varying connectivity patterns resulting
      from the application of both DTF and PDC. Two different cortical networks were
      detected with the proposed methods, one constant across the task and the other
      evolving during the preparation of the joint movement.

PMID- 18334382
TI  - Entropy-based optimization of wavelet spatial filters.
AB  - A new class of spatial filters for surface electromyographic (EMG) signal
      detection is proposed. These filters are based on the 2-D spatial wavelet
      decomposition of the surface EMG recorded with a grid of electrodes and inverse
      transformation after zeroing a subset of the transformation coefficients. The
      filter transfer function depends on the selected mother wavelet in the two
      spatial directions. Wavelet parameterization is proposed with the aim of signal
      based optimization of the transfer function of the spatial filter. The
      optimization criterion was the minimization of the entropy of the time samples of
      the output signal. The optimized spatial filter is linear and space invariant. In
      simulated and experimental recordings, the optimized wavelet filter showed
      increased selectivity with respect to previously proposed filters. For example,
      in simulation, the ratio between the peak-to-peak amplitude of action potentials
      generated by motor units 20 degrees apart in the transversal direction was 8.58%
      (with monopolar recording), 2.47% (double differential), 2.59% (normal double
      differential), and 0.47% (optimized wavelet filter). In experimental recordings,
      the duration of the detected action potentials decreased from (mean +/- SD) 6.9
      +/- 0.3 ms (monopolar recording), to 4.5 +/- 0.2 ms (normal double differential),
      3.7 +/- 0.2 (double differential), and 3.0 +/- 0.1 ms (optimized wavelet filter).
      In conclusion, the new class of spatial filters with the proposed signal-based
      optimization of the transfer function allows better discrimination of individual
      motor unit activities in surface EMG recordings than it was previously possible.

PMID- 18334383
TI  - Error-related EEG potentials generated during simulated brain-computer
      interaction.
AB  - Brain-computer interfaces (BCIs) are prone to errors in the recognition of
      subject's intent. An elegant approach to improve the accuracy of BCIs consists in
      a verification procedure directly based on the presence of error-related
      potentials (ErrP) in the electroencephalogram (EEG) recorded right after the
      occurrence of an error. Several studies show the presence of ErrP in typical
      choice reaction tasks. However, in the context of a BCI, the central question is:
      "Are ErrP also elicited when the error is made by the interface during the
      recognition of the subject's intent?"; We have thus explored whether ErrP also
      follow a feedback indicating incorrect responses of the simulated BCI interface.
      Five healthy volunteer subjects participated in a new human-robot interaction
      experiment, which seem to confirm the previously reported presence of a new kind
      of ErrP. However, in order to exploit these ErrP, we need to detect them in each
      single trial using a short window following the feedback associated to the
      response of the BCI. We have achieved an average recognition rate of correct and
      erroneous single trials of 83.5% and 79.2%, respectively, using a classifier
      built with data recorded up to three months earlier.

PMID- 18334384
TI  - EMG-based speech recognition using hidden markov models with global control
      variables.
AB  - It is well known that a strong relationship exists between human voices and the
      movement of articulatory facial muscles. In this paper, we utilize this knowledge
      to implement an automatic speech recognition scheme which uses solely surface
      electromyogram (EMG) signals. The sequence of EMG signals for each word is
      modelled by a hidden Markov model (HMM) framework. The main objective of the work
      involves building a model for state observation density when multichannel
      observation sequences are given. The proposed model reflects the dependencies
      between each of the EMG signals, which are described by introducing a global
      control variable. We also develop an efficient model training method, based on a
      maximum likelihood criterion. In a preliminary study, 60 isolated words were used
      as recognition variables. EMG signals were acquired from three articulatory
      facial muscles. The findings indicate that such a system may have the capacity to
      recognize speech signals with an accuracy of up to 87.07%, which is superior to
      the independent probabilistic model.

PMID- 18334385
TI  - Multiplicative correction of subject effect as preprocessing for analysis of
      variance.
AB  - The procedure of repeated-measures ANOVA assumes the linear model in which
      effects of both subjects and experimental conditions are additive. However, in
      electroencephalography and magnetoencephalography, there may be situations where
      subject effects should be considered to be multiplicative in amplitude. We
      propose a simple method to normalize such data by multiplying each subject's
      response by a subject-specific constant. This paper derives ANOVA tables for such
      normalized data. Present simulations show that this method performs ANOVA
      effectively including multiple comparisons provided that the data follows the
      multiplicative model.

PMID- 18334386
TI  - Fractional delay estimation for blind source separation and localization of
      temporomandibular joint sounds.
AB  - Temporomandibular joint (TMJ) sound sources are generated from the two joints
      connecting the lower jaw to the temporal bone. Such sounds are important
      diagnostic signs in patients suffering from temporomandibular disorder (TMD). In
      this study, we address the problem of source separation of the TMJ sounds. In
      particular, we examine patients with only one TMJ generating "clicks".
      Thereafter, we consider the TMJ sounds recorded from the two auditory canals as
      mixtures of clicks from the TMD joint and the noise produced by the other
      healthy/normal TMJ. We next exploit the statistical nonstationary nature of the
      TMJ signals by employing the degenerate unmixing estimation technique (DUET)
      algorithm, a time-frequency (T-F) approach to separate the sources. As the DUET
      algorithm requires the sensors to be closely spaced, which is not satisfied by
      our recording setup, we have to estimate the delay between the recorded TMJ
      sounds to perform an alignment of the mixtures. Thus, the proposed extension of
      DUET enables an essentially arbitrary separation of the sensors. It is also shown
      that DUET outperforms the convolutive Infomax algorithm in this particular TMJ
      source separation scenario. The spectra of both separated TMJ sources with our
      method are comparable to those available in existing literature. Examination of
      both spectra suggests that the click source has a better audible prominence than
      the healthy TMJ source. Furthermore, we address the problem of source
      localization. This can be achieved automatically by detecting the sign of our
      proposed mutual information estimator which exhibits a maximum at the delay
      between the two mixtures. As a result, the localized separated TMJ sources can be
      of great clinical value to dental specialists.

PMID- 18334387
TI  - Exploring the variability of single trials in somatosensory evoked responses
      using constrained source extraction and RMT.
AB  - This paper describes the theoretical background of a new data-driven approach to
      encephalographic single-trial (ST) data analysis. Temporal constrained source
      extraction using sparse decomposition identifies signal topographies that closely
      match the shape characteristics of a reference signal, one response for each ST.
      The correlations between these ST topographies are computed for formal
      Correlation Matrix Analysis (CMA) based on Random Matrix Theory (RMT). The RMT
      CMA provides clusters of similar ST topologies in a completely unsupervised
      manner. These patterns are then classified into deterministic set and noise using
      well established RMT results. The efficacy of the method is applied to EEG and
      MEG data of somatosensory evoked responses (SERs). The results demonstrate that
      the method can recover brain signals with time course resembling the reference
      signal and follow changes in strength and/or topography in time by simply
      stepping the reference signal through time.

PMID- 18334388
TI  - Fast nonlinear image reconstruction for scanning impedance imaging.
AB  - Scanning (electrical) impedance imaging (SII) is a novel high-resolution imaging
      modality that has the potential of imaging the electrical properties of thin
      biological tissues. In this paper, we apply the reciprocity principle to the
      modeling of the SII system and develop a fast nonlinear inverse method for image
      reconstruction. The method is fast because it uses convolution to eliminate the
      requirement of a numerical solver for the 3-D electrostatic field in the SII
      system. Numerical results show that our approach can accurately reveal the exact
      conductivity distribution from the measured current map for different 2-D
      simulation phantoms. Experiments were also performed using our SII system for a
      piece of butterfly wing and breast cancer cells. Two-dimensional current images
      were measured and corresponding quantitative conductivity images were restored
      using our approach. The reconstructed images are quantitative and reveal details
      not present in the measured images.

PMID- 18334389
TI  - Validation of finite element models of liver tissue using micro-CT.
AB  - In this work, we aim at validating some soft tissue deformation models using high
      resolution micro-computed tomography (Micro-CT) images. The imaging technique
      plays a key role in detecting the tissue deformation details in the contact
      region between the tissue and the surgical tool (probe) for small force loads and
      provides good capabilities of creating accurate 3-D models of soft tissues.
      Surgical simulations rely on accurate representation of the mechanical response
      of soft tissues subjected to surgical manipulations. Several finite-element
      models have been suggested to characterize soft tissues. However, validating
      these models for specific tissues still remain a challenge. In this study, ex
      vivo lamb liver tissue is chosen to validate the linear elastic model (LEM), the
      linear viscoelastic model (LVEM), and the neo-Hooke hyperelastic model (NHM). We
      find that the LEM is more applicable to lamb liver than the LVEM for smaller
      force loads (< 20 g) and that the NHM is closer to reality than the LVEM for the
      range of force loads from 5 to 40 g.

PMID- 18334390
TI  - Quantification of regional left ventricular dyssynchrony by magnetic resonance
      imaging.
AB  - Cardiac resynchronization therapy is an established treatment in patients with
      symptomatic heart failure and intraventricular conduction delay. Electrical
      dyssynchrony is typically adopted to represent myocardial activation
      dyssynchrony, which should be compensated by cardiac resynchronization therapy.
      One third of the patients, however, does not respond to the therapy. Therefore,
      imaging modalities aimed at the mechanical dyssynchrony estimation have been
      recently proposed to improve patient selection criteria. This paper presents a
      novel fully automated method for regional mechanical left ventricular
      dyssynchrony quantification in short-axis magnetic resonance imaging. The
      endocardial movement is described by time-displacement curves with respect to an
      automatically determined reference point. Different methods are proposed for time
      displacement curve analysis aimed at the regional contraction timing estimation.
      These methods were evaluated in two groups of subjects with (nine patients) and
      without (six patients) left bundle branch block. The contraction timing standard
      deviation showed a significant increase for left bundle branch block patients
      with all the methods. A novel method based on phase spectrum analysis may be
      however preferred due to a better specificity (99.7%) and sensitivity (99.0%). In
      conclusion, this method provides a valuable prognostic indicator for heart
      failure patients with dyssynchronous ventricular contraction and it opens new
      possibilities for regional timing analysis.

PMID- 18334391
TI  - A novel angiographic methodology for the quantification of angiogenesis.
AB  - The objective is to develop a method to quantify the dynamic information of
      contrast transport using angiography for investigating angiogenic treatments. In
      the rabbit hindlimb ischemia model, contrast media transport was examined for
      both arteries and the microvasculature. Time histories of image intensity were
      constructed and modeled. The differences in contrast transport quantified by the
      parameters of the mathematical model were statistically compared between animals
      treated with an adenoviral vector that expressed vascular endothelial growth
      factor and untreated animals. The data reveal that after one week of ischemia,
      treated animals have a statistical increase in the number of large vessels that
      convect blood more efficiently. This analysis further shows a statistically
      significant increase in the angiographic blush in the treated animals. A
      methodology is described that offers the capability of examining the number and
      geometry of large arteries, the dynamics of contrast transport, and the amount of
      angiographic blush that is related to microvascular density. In therapeutic
      angiogenesis, numerous techniques are used to measure variables such as the
      angiographic score, capillary density, and regional blood flow. The analysis
      presented herein can offer information of these variables, and is transferable
      from the laboratory to the clinical arena.

PMID- 18334392
TI  - Dynamics of MRI-Guided thermal ablation of VX2 tumor in paraspinal muscle of
      rabbits.
AB  - This study combines fast magnetic resonance imaging (MRI) and model simulation of
      tissue thermal ablation for monitoring and predicting the dynamics of lesion size
      for tumor destruction. In vivo experiments were conducted using radiofrequency
      (RF) thermal ablation in paraspinal muscle of rabbit with a VX2 tumor. Before
      ablation, turbo-spin echo (TSE) images visualized the 3-D tumor (necrotic core
      and tumor periphery) and surrounding normal tissue. MR gradient-recalled echo
      (GRE) phase and magnitude images were acquired repeatedly in 3.3 s at 30-s
      intervals during and after thermal ablation to follow tissue temperature
      distribution dynamics and lesion development in tumor and surrounding normal
      tissue. Final lesion sizes estimated from GRE magnitude, post-ablation TSE, and
      stained histologic images were compared. Model simulations of temperature
      distribution and lesion development dynamics closely corresponded to the
      experimental data from MR images in tumor and normal tissue. The combined use of
      MR image monitoring and model simulation has the potential for improving
      pretreatment planning and real-time prediction of lesion-size dynamics for
      guidance of thermal ablation of tumors.

PMID- 18334393
TI  - Multiple-instance learning algorithms for computer-aided detection.
AB  - Many computer-aided diagnosis (CAD) problems can be best modelled as a multiple
      instance learning (MIL) problem with unbalanced data, i.e., the training data
      typically consists of a few positive bags, and a very large number of negative
      instances. Existing MIL algorithms are much too computationally expensive for
      these datasets. We describe CH, a framework for learning a Convex Hull
      representation of multiple instances that is significantly faster than existing
      MIL algorithms. Our CH framework applies to any standard hyperplane-based
      learning algorithm, and for some algorithms, is guaranteed to find the global
      optimal solution. Experimental studies on two different CAD applications further
      demonstrate that the proposed algorithm significantly improves diagnostic
      accuracy when compared to both MIL and traditional classifiers. Although not
      designed for standard MIL problems (which have both positive and negative bags
      and relatively balanced datasets), comparisons against other MIL methods on
      benchmark problems also indicate that the proposed method is competitive with the
      state-of-the-art.

PMID- 18334394
TI  - Multiscale penalized weighted least-squares sinogram restoration for low-dose x
      ray computed tomography.
AB  - In this paper, we propose a novel multiscale penalized weighted least-squares
      (PWLS) method for restoration of low-dose computed tomography (CT) sinogram. The
      method utilizes wavelet transform for the multiscale or multiresolution analysis
      on the sinogram. Specifically, the Mallat-Zhong's wavelet transform is applied to
      decompose the sinogram to different resolution levels. At each decomposed
      resolution level, a PWLS criterion is applied to restore the noise-contaminated
      wavelet coefficients, where the penalty is adaptive to each resolution scale and
      the weight is updated by an exponential relationship between the data variance
      and mean at each scale and location. The proposed PWLS method is based on the
      observations that 1) noise in the CT sinogram after logarithm transform and
      calibration can be modeled as signal-dependent variables and the sample variance
      depends on the sample mean by an exponential relationship; and 2) noise reduction
      can be more effective when it is adaptive to different resolution levels. The
      effectiveness of the proposed multiscale PWLS method is validated by both
      computer simulations and experimental studies. The gain by multiscale approach
      over single scale means is quantified by noise-resolution tradeoff measures.

PMID- 18334395
TI  - Tethered capsule endoscopy, a low-cost and high-performance alternative
      technology for the screening of esophageal cancer and Barrett's esophagus.
AB  - Esophageal cancer is currently the fastest growing cancer in the United States.
      To help combat the recent rise in morbidity, our laboratory has developed a low
      cost tethered capsule endoscope system (TCE) aimed at improving early detection
      of esophageal cancer. The TCE contains a resonant fiberoptic laser scanner (1.6
      mm O.D.) which fits into 6.4-mm easy-to-swallow capsule at the distal tip. The
      tethered portion contains a single mode optical fiber multiplexed to three laser
      diodes at the proximal end. This design offers two main advantages over current
      endoscope technology. First, because of its small size, the TCE can be swallowed
      with minimal patient discomfort, thereby obviating sedation. Second, by imaging
      via directed laser light, the TCE is strategically positioned to employ several
      burgeoning laser-based diagnostic technologies, such as narrow-band,
      hyperspectral, and fluorescence imaging. It is believed that the combination of
      such imaging techniques with novel biomarkers of dysplasia will greatly assist in
      identifying precancerous conditions such as Barrett's esophagus (BE). As the
      probe is swallowed, the fiber scanner captures high resolution, wide-field color
      images of the gastroesophageal junction (500 lines at 0.05-mm resolution)
      currently at 15-Hz frame rate. Video images are recorded as the capsule is slowly
      retracted by its tether. Accompanying software generates panoramic images from
      the video output by mosaicing individual frames to aid in pattern recognition.
      This initial report describes the rationale for the unique TCE system design,
      results from preliminary testing in vitro and in vivo, and discussion on the
      merits of this new platform technology as a basis for developing a low-cost
      screening program for esophageal cancer.

PMID- 18334396
TI  - User-modulated impedance control of a prosthetic elbow in unconstrained,
      perturbed motion.
AB  - Humans use the agonist-antagonist structure of their muscles to simultaneously
      determine both the motion and the stiffness of their joints. Designing this
      feature into an artificial limb may prove advantageous. To evaluate the
      performance of an artificial limb capable of modulating its impedance, we have
      created a compact series elastic actuator that has the same size and similar
      weight as commercially available electric prosthetic elbows. The inherent
      compliance in series elastic actuators ensure their safety to the user, even at
      high speeds, while creating a high-fidelity force actuator ideally suited for
      impedance control. This paper describes three serial studies that build on each
      other. The first study presents modeling of the actuator to ensure stability in
      the range of impedance modulation and empirically tests the actuator to validate
      its ability to modulate impedance. The actuator is found to be stable and
      accurate over a wide range of impedances. In the second study, four subjects are
      tested in a preliminary experiment to answer basic questions necessary to
      implement user-modulated impedance control. Findings include the superiority of
      velocity control over position control as the underlying motion paradigm and the
      preference for high stiffness and non-negative inertia. Based on the findings of
      the second study, the third study evaluates the performance of 15 able-bodied
      subjects for two tasks, using five different impedance paradigms. Impedance
      modulation, speed, and error were compared across paradigms. The results indicate
      that subjects do not actively modulate impedance if it is near a preferred
      baseline. Fixed impedance and viscosity modulation provide the most accurate
      control.

PMID- 18334397
TI  - Dynamic current density of the disk electrode double-layer.
AB  - With applied potential, the current distribution at the surface of a disk
      electrode is spatially nonuniform and time dependent. This distribution is
      important to control in applications that desire a uniform current density
      profile or minimal corrosion. We examine the current density profile of a
      capacitive disk electrode subjected to a voltage-step using finite element
      analysis software to solve the system of partial differential equations. In
      detailed analyses we show quantitatively that the current density shifts from
      peripheral enhancement to near-uniformity following 1/2 of the lumped element
      time constant. As charging continues, the current density is slightly enhanced in
      the central region. We present curves for the evolution of local "time constants"
      as time progresses and calculate their effective values. The model is intended to
      be the basis of future work to control the corrosion profile of biologically
      implantable electrodes of arbitrary shape. Data suggest a means to control
      corrosion by retarding the edges of a stimulus pulse. Additionally, smaller
      electrodes may be more effective in fully utilizing surface area for charge
      transfer due to their shorter time constants.

PMID- 18334398
TI  - Painless drug delivery through microneedle-based transdermal patches featuring
      active infusion.
AB  - This paper presents the first microneedle-based transdermal patch with integrated
      active dispensing functionality. The electrically controlled system consists of a
      low-cost dosing and actuation unit capable of controlled release of liquid in the
      microliter range at low flow-rates and minimally invasive, side-opened,
      microneedles. The system was successfully tested in vivo by insulin
      administration to diabetic rats. Active infusion of insulin at 2 mul/h was
      compared to passive, diffusion-driven, delivery. Continuous active infusion
      caused significantly higher insulin concentrations in blood plasma. After a 3-h
      delivery period, the insulin concentration was five times larger compared to
      passive delivery. Consistent with insulin concentrations, actively administered
      insulin resulted in a significant decrease of blood glucose levels. Additionally,
      insertion and liquid injection was verified on human skin. This study shows the
      feasibility of a patch-like system with on-board liquid storage and dispensing
      capability. The proposed device represents a first step towards painless and
      convenient administration of macromolecular drugs such as insulin or vaccines.

PMID- 18334399
TI  - An automated carotid pulse assessment approach using Doppler ultrasound.
AB  - During cardiac arrest emergencies, lay rescuers are required to manually check
      the patient's carotid pulse after the delivery of defibrillation shocks to assess
      the cardiac resuscitation progress of the patient. As a more automated way of
      monitoring the resuscitation progress, a new Doppler-ultrasound-based carotid
      pulse assessment approach is presented in this paper. The method works by
      analyzing the temporal aperiodicity of Doppler shifts seen in the ultrasound
      echoes returned from the patient's carotid arteries. As a quantitative
      investigation with this method, we derived a new measure called the pulselessness
      indicator to assess whether a carotid pulse is absent based on the given Doppler
      information. To study the performance of the new carotid pulse checking method,
      we built a multi-channel CW Doppler prototype device to acquire Doppler data in
      vivo during cardiac arrest experiments conducted on five different swines and
      computed pulselessness indicator estimates with these data. Our results indicated
      that the Doppler-based pulse checking approach has good sensitivity and
      specificity: it had a pulselessness detection rate greater than 0.9 for a given
      false alarm rate of 0.05. As a further analysis, the prototype device was applied
      to other experiments where the swine had suffered cardiac arrest for over five
      minutes. It showed a consistent assessment performance on the monitoring of the
      swine's resuscitation progress after defibrillation and chest compressions.

PMID- 18334400
TI  - A high-precision contrast injector for small animal x-ray digital subtraction
      angiography.
AB  - The availability of genetically altered animal models of human disease for basic
      research has generated great interest in new imaging methodologies. Digital
      subtraction angiography (DSA) offers an appealing approach to functional imaging
      in small animals because of the high spatial and temporal resolution, and the
      ability to visualize and measure blood flow. The micro-injector described here
      meets crucial performance parameters to ensure optimal vessel enhancement without
      significantly increasing the total blood volume or producing overlap of enhanced
      structures. The micro-injector can inject small, reproducible volumes of contrast
      agent at high flow rates with computer-controlled timing synchronized to
      cardiopulmonary activity. Iterative bench-top and live animal experiments with
      both rat and mouse have been conducted to evaluate the performance of this
      computer-controlled micro-injector, a first demonstration of a new device
      designed explicitly for the unique requirements of DSA in small animals.
      Injection protocols were optimized and screened for potential physiological
      impact. For the optimized protocols, we found that changes in the time-density
      curves for representative regions of interest in the thorax were due primarily to
      physiological changes, independent of micro-injector parameters.

PMID- 18334401
TI  - Spatio-temporal reconstruction of bilateral auditory steady-state responses using
      MEG beamformers.
AB  - A rapidly growing number of neuromagnetic studies focus on the analysis of
      auditory steady-state responses (ASSR) in relation to a diverse array of factors
      including age, selective attention, and presence of psychopathology. The
      objectives of these studies require accurate spatio-temporal estimation of the
      underlying neural generators, a challenging task due to the relatively low signal
      strength and high correlation between bilateral auditory cortical sources. This
      paper evaluates the performance of two beamforming schemes that can potentially
      overcome such difficulties: 1) the linearly constrained minimum variance
      beamformer with partial sensor coverage (LCMV-PSC), and 2) the multiple
      constrained minimum-variance beamformer with coherent source region suppression
      (MCMV-CSRS). Simulation experiments are conducted to assess the impact of source
      parameters on the reconstruction accuracy. The results indicate that the LCMV-PSC
      method is prone to localization errors that essentially occur along medio-lateral
      directions, increase with source depth, and are associated to amplitude and phase
      distortions of the estimated time courses of activity. Comparatively, the MCMV
      CSRS method exhibits precise localization and minimal amplitude and phase
      distortion for a broad range of relative interferer's positions within the
      suppression region. The results from the numerical experiments are validated on
      real magnetoencephalographic (MEG) data collected from a 40-Hz ASSR paradigm.

PMID- 18334402
TI  - Array response kernels for EEG and MEG in multilayer ellipsoidal geometry.
AB  - We present forward modeling solutions in the form of array response kernels for
      electroencephalography (EEG) and magnetoencephalography (MEG), assuming that a
      multilayer ellipsoidal geometry approximates the anatomy of the head and a dipole
      current models the source. The use of an ellipsoidal geometry is useful in cases
      for which incorporating the anisotropy of the head is important but a better
      model cannot be defined. The structure of our forward solutions facilitates the
      analysis of the inverse problem by factoring the lead field into a product of the
      current dipole source and a kernel containing the information corresponding to
      the head geometry and location of the source and sensors. This factorization
      allows the inverse problem to be approached as an explicit function of just the
      location parameters, which reduces the complexity of the estimation solution
      search. Our forward solutions have the potential of facilitating the solution of
      the inverse problem, as they provide algebraic representations suitable for
      numerical implementation. The applicability of our models is illustrated with
      numerical examples on real EEG/MEG data of N20 responses. Our results show that
      the residual data after modeling the N20 response using a dipole for the source
      and an ellipsoidal geometry for the head is in average lower than the residual
      remaining when a spherical geometry is used for the same estimated dipole.

PMID- 18334403
TI  - Performance of prewhitening beamforming in MEG dual experimental conditions.
AB  - This paper presents an analysis on the performance of the prewhitening beamformer
      when applied to magnetoencephalography (MEG) experiments involving dual (task and
      control) conditions. We first analyze the method's robustness to two types of
      violations of the prerequisites for the prewhitening method that may arise in
      real-life two-condition experiments. In one type of violation, some sources exist
      only in the control condition but not in the task condition. In the other type of
      violation, some signal sources exist both in the control and the task conditions,
      and that they change intensity between the two conditions. Our analysis shows
      that the prewhitening method is very robust to these nonideal conditions. In this
      paper, we also present a theoretical analysis showing that the prewhitening
      method is considerably insensitive to overestimation of the signal-subspace
      dimensionality. Therefore, the prewhitening beamformer does not require accurate
      estimation of the signal subspace dimension. Results of our theoretical analyses
      are validated in numerical experiments and in experiments using a real MEG data
      set obtained during self-paced hand movements.

PMID- 18334404
TI  - Current distance relations for fiber stimulation with pointsources.
AB  - The following results are based on computer simulations and on activating
      function analysis. In the near field, denervated muscle fibers as well as nerve
      fibers with a sealed ending are easier to stimulate in the central region than
      with electrodes close to the end. When electrode-fiber distance is increased, the
      electrode location for optimal stimulation efficacy shifts from a central
      position to a region beyond the fiber end for cathodic stimulation and to a
      position above the terminating part of the fiber for anodic currents. The
      phenomenon becomes more pronounced with increasing distance between the electrode
      and fiber axis, because in the far field, the current-distance relation changes
      from quadratic to cubic, whereas stimulation at the fiber end obeys a rather
      constant quadratic law.

PMID- 18334405
TI  - Online electromyographic control of a robotic prosthesis.
AB  - This paper presents a two-part study investigating the use of forearm surface
      electromyographic (EMG) signals for real-time control of a robotic arm. In the
      first part of the study, we explore and extend current classification-based
      paradigms for myoelectric control to obtain high accuracy (92-98%) on an eight
      class offline classification problem, with up to 16 classifications/s. This
      offline study suggested that a high degree of control could be achieved with very
      little training time (under 10 min). The second part of this paper describes the
      design of an online control system for a robotic arm with 4 degrees of freedom.
      We evaluated the performance of the EMG-based real-time control system by
      comparing it with a keyboard-control baseline in a three-subject study for a
      variety of complex tasks.

PMID- 18334406
TI  - Microchannels as axonal amplifiers.
AB  - An implantable neural interface capable of reliable long-term high-resolution
      recording from peripheral nerves has yet to be developed. Device design is
      challenging because extracellular axonal signals are very small, decay rapidly
      with distance from the axon, and in myelinated fibres are concentrated close to
      nodes of Ranvier, which are around 1 mum long and spaced several hundred
      micrometers apart. We present a finite element model examining the electrical
      behavior of axons in microchannels, and demonstrate that confining axons in such
      channels substantially amplifies the extracellular signal. For example, housing a
      10-microm myelinated axon in a 1-cm-long channel with a 1000-microm(2) cross
      section is predicted to generate a peak extracellular voltage of over 10 mV.
      Furthermore, there is little radial signal decay within the channel, and a smooth
      axial variation of signal amplitude along the channel, irrespective of node
      location. Additional benefits include a greater extracellular voltage generated
      by large myelinated fibres compared to small unmyelinated axons, and the
      reduction of gain to unity at the end of the channel which ensures that there can
      be no crosstalk with electrodes in other channels nearby. A microchannel
      architecture seems well suited to the requirements of a peripheral nerve
      interface.

PMID- 18334407
TI  - BCI competition III: dataset II- ensemble of SVMs for BCI P300 speller.
AB  - Brain-computer interface P300 speller aims at helping patients unable to activate
      muscles to spell words by means of their brain signal activities. Associated to
      this BCI paradigm, there is the problem of classifying electroencephalogram
      signals related to responses to some visual stimuli. This paper addresses the
      problem of signal responses variability within a single subject in such brain
      computer interface. We propose a method that copes with such variabilities
      through an ensemble of classifiers approach. Each classifier is composed of a
      linear support vector machine trained on a small part of the available data and
      for which a channel selection procedure has been performed. Performances of our
      algorithm have been evaluated on dataset II of the BCI Competition III and has
      yielded the best performance of the competition.

PMID- 18334408
TI  - A multidimensional classification approach for the automated analysis of flow
      cytometry data.
AB  - We describe an automated multidimensional approach for the analysis of flow
      cytometry data based on pattern classification. Flow cytometry is a widely used
      technique both for research and clinical purposes where it has become essential
      for the diagnosis and follow up of a wide spectrum of diseases, such as HIV
      infection and neoplastic disorders. Flow cytometry data sets are composed of
      quite a large number of observations that can be viewed as elements of a n
      dimensional space. The aim of the analysis of such data files is typically to
      classify groups of cellular events as specific populations with biological
      meaning. Despite significant improvements in data acquisition capabilities of
      flow cytometers, data analysis is still based on bi-dimensional strategies which
      were defined a long time ago. These are strongly dependent on the expertise of an
      expert operator, this approach being relatively subjective and potentially
      leading to unreliable results. Automated analysis of flow cytometry data is an
      essential step to improve reproducibility of the results. The proposed automated
      analysis was implemented on peripherial blood lymphocyte subsets from 307 samples
      stained and prepared in an identical way and it was capable of identifying all
      cell subsets present in each sample studied that could also be detected in the
      same data files by an expert operator. A highly significant correlation was found
      between the results obtained by an expert operator using a conventional manual
      method of analysis and those obtained using the implemented automated approach.

PMID- 18334409
TI  - Heart rate detection from plantar bioimpedance measurements.
AB  - In this paper, a novel technique for heart rate measurement on a standing subject
      is proposed that relies on electrical impedance variations detected by a plantar
      interface with booth feet, such as those in some bathroom weighting scales for
      body composition analysis. Heart-related impedance variations in the legs come
      from arterial blood circulation and are below 500 mOmega. To detect them, we have
      implemented a system with a gain in excess of 600, and whose fully differential
      AC input amplifier has a gain of 4.5 and a common-mode rejection ratio (CMRR)
      higher than 90 dB at 10 kHz. Differential coherent demodulation based on
      synchronous sampling yields a signal-to-noise ratio (SNR) of about 54 dB . The
      system sensitivity is 610 mV/Omega. The technique has been demonstrated on 18
      volunteers, whose bioimpedance signal and ECG were simultaneously recorded. A
      Bland-Altman plot shows a mean bias of -0.2 ms between the RR time intervals
      obtained from these two signals, which is negligible. The technique is simple and
      user friendly and does not require any additional sensors or electrodes attached
      to the body, hence no conductive gel or skin preparation.

PMID- 18334410
TI  - Application of thermography for non-invasive diagnosis of thyroid gland disease.
AB  - In this paper, a computer-based prototype device was designed based on an
      economical noninvasive system that could detect and display the relative skin
      temperature variations present in human patients suffering from thyroid
      disorders. Such a system could be used to augment the normal procedures followed
      by the physician in diagnosing the thyroid to detect areas of hyperactivity
      within the gland. Because a hyperactive nodule is a center of increased blood
      flow and chemical activity, it might be also a center of heat production that is
      detectable by thermal sensing. This paper also presents a finite-element analysis
      (FEA) of a hot thyroid nodule that is used for investigating the temperature
      distribution in conjunction with the prototype. The instrumentation model built
      was based on actual dimensional human model for thyroid nodules obtained from
      various patients. A software program was written in Visual Basic to detect the
      temperature distribution around the hot spot. The software also incorporates
      means to minimize the thermal noise associated with the body temperature. The FEA
      utilizes the same boundary values used in the practical settings. This includes
      initial values of temperatures for the hot spot and its surroundings. The results
      of the finite-element simulation assisted in the selection of the solid state
      sensors that were used in the instrumentation of the thermographic system. The
      selected sensors were calibrated for their functionality and dynamic performance
      according to the specifications. The new noninvasive diagnostic technique was
      applied to patients having Graves' diseases at the Indiana University (IU)
      Hospital, and compared with the existing scheme that utilizes I Scan. The results
      of the new diagnostic method were in good agreement with the current existing
      method.

PMID- 18334411
TI  - Predictive haemodynamics in a one-dimensional human carotid artery bifurcation.
      Part II: Application to graft design.
AB  - A Bayesian surrogate modeling technique is proposed that may be able to predict
      an optimal bypass graft configuration for patients suffering with stenosis in the
      internal carotid artery (ICA). At the outset, this statistical technique is
      considered as a means for identifying key geometric parameters influencing
      haemodynamics in the human carotid bifurcation. This methodology uses a design of
      experiments (DoE) technique to generate candidate geometries for flow analysis. A
      pulsatile one dimensional Navier-Stokes solver incorporating fluid-wall
      interactions for a Newtonian fluid which predicts pressure and flow in the
      carotid bifurcation (comprising a stenosed segment in the internal carotid
      artery) is used for the numerical simulations. Two metrics, pressure variation
      factor (PVF) and maximum pressure (p(*)(m)) are employed to directly compare the
      global and local effects, respectively, of variations in the geometry. The values
      of PVF and p(*)(m) are then used to construct two Bayesian surrogate models.
      These models are statistically analyzed to visualize how each geometric parameter
      influences PVF and p(*)(m). Percentage of stenosis is found to influence these
      pressure based metrics more than any other geometric parameter. Later, we
      identify bypass grafts with optimal geometric and material properties which have
      low values of PVF on five test cases with 70%, 75%, 80%, 85%, and 90% stenosis in
      the ICA, respectively.5%, 80%, 85%, and 90% stenosis in the ICA, respectively.

PMID- 18334412
TI  - Dental magnetic attachment: toward third generation devices.
AB  - Toward realizing the performance of functional and versatile dental magnetic
      attachments in the third generation required for individual prosthesis, it is
      important to control retentive characteristics of the attachments. For this
      purpose, three new types of magnetic attachment, i.e., split-pole type with a
      slant magnetization, modified split-pole type, and cylinder type, have been
      developed and evaluated in terms of the restoring force as well as the retentive
      force. The new attachments are designed to have high corrosion resistance,
      combining magnetic and nonmagnetic stainless steels and microlaser welding
      similar to the usual cup-yoke and sandwich-yoke types. It has been found that the
      two split-pole types have stronger restoring force and the cylinder type has
      weaker restoring force in comparison with the usual magnetic attachments. The
      attachments can be used properly and selectively according to individual
      requirement on abutment state and denture retention. As a result, the newly
      developed attachments may provide flexible retention performance useful for more
      effective and extensive applications of a magnetic attachment.

PMID- 18334413
TI  - Continuous monitoring of sonomyography, electromyography and torque generated by
      normal upper arm muscles during isometric contraction: sonomyography assessment
      for arm muscles.
AB  - The aim of this study is to demonstrate the feasibility of using the continuous
      signals about the thickness and pennation angle changes of muscles detected in
      real-time from ultrasound images, named as sonomyography (SMG), to characterize
      muscles under isometric contraction, along with synchronized surface
      electromyography (EMG) and generated torque signals. The right biceps brachii
      muscles of seven normal young adult subjects were tested. We observed that
      exponential functions could well represent the relationships between the
      normalized EMG root-mean-square (RMS) and the torque, the RMS and the muscle
      deformation SMG, and the RMS and the pennation angle SMG for the data of the
      contraction phase, with exponent coefficients of 0.0341 +/- 0.0148 (Mean SD),
      0.0619 +/- 0.0273, and 0.0266 +/- 0.0076, respectively. In addition, the
      preliminary results also demonstrated linear relationships between the normalized
      torque and the muscle deformation as well as the pennation angle with the ratios
      of 9 .79 +/- 3.01 and 2.02 +/- 0.53, respectively. The overall mean R2 for the
      regressions was approximately 0.9 and the overall mean relative root mean square
      error (RRMSE) smaller than 15%. The potential values of SMG together with EMG to
      provide a more comprehensive assessment for the muscle functions should be
      further investigated with more subjects and more muscle groups.

PMID- 18334414
TI  - Validation and application of a computational model for wrist and hand movements
      using surface markers.
AB  - A kinematic model is presented based on surface marker placement generating
      wrist, metacarpal arch, fingers and thumb movements. Standard calculations are
      used throughout the model and then applied to the specified marker placement. A
      static trial involving eight unimpaired participants was carried out to assess
      inter-rater reliability. The standard deviations across the data were comparable
      to manual goniometers. In addition, a test-retest trial of ten unimpaired
      participants is also reported to illustrate the variability of movement at the
      wrist joint, metacarpal arch, and index finger as an example of model output when
      repeating the same task many times. Light and heavyweight versions of the tasks
      are assessed and characteristics of individual movement strategies presented. The
      participant trial showed moderate correlation in radial/ulnar deviation of the
      wrist (r = 0.65), and strong correlation in both metacarpal arch joints (r = 0.75
      and r = 0.85), the MCP (r = 0.79), and PIP (r = 0.87) joints of the index finger.
      The results indicate that individuals use repeated strategies of movement when
      lifting light and heavyweight versions of the same object, but showed no obvious
      repeated pattern of movement across the population.

PMID- 18334415
TI  - Penetration and precision of subsurface photodisruption in porcine skin tissue
      with infrared femtosecond laser pulses.
AB  - The surgical precision of photodisruption with ultrafast optical pulses depends
      on the accurate delivery of optical energy to sites of interest. As light
      penetration is limited in turbid tissues, localization and precision of
      subsurface breakdown highly depend on the interacting effects of increased power
      requirements and external focusing conditions. Infrared femtosecond breakdown
      extent in excised porcine skin tissue was investigated using a high-frequency
      ultrasonic technique which sensitively detected laser-induced bubbles. Using a
      focused laser source, optical parameters including laser fluence and focusing
      numerical aperture (NA) were controlled. Decreasing NA improved penetration,
      while increasing NA improved precision. At lower NA, penetrations of up to 1 mm
      could be achieved with a single laser excitation at the cost of an expanded
      breakdown region which reduced precision. Even at higher NA, however, maximum
      penetration reduced to 400 microm and precision was still limited with extended
      breakdown regions for focusing depths greater than 100 microm. Glycerol was used
      as an index matching material, which helped reduce scattering and improved
      penetration by 150 to 400 microm for all NAs. Nonetheless, multiple breakdown
      sites and the corresponding reduction in precision were observed even with
      glycerol treatment.

PMID- 18334416
TI  - A detector for a chronic implantable atrial tachyarrhythmia monitor.
AB  - Continuous long-term monitoring of atrial fibrillation (AF) and tachycardia (AT)
      is an unmet clinical need, which could be met with a chronically-implanted
      monitor. Improved therapeutic decisions based on accurate monitoring of
      parameters, such as daily AF/AT burden (hours/ day) may lead to improvements in
      clinical outcomes such as reduction in hospitalizations, symptoms, and strokes.
      This paper describes an AF/AT detector that detects AF as well as AT with an
      irregular ventricular response, and a supplementary AT detector for AT with more
      regular ventricular response. Seven databases with significant durations of AF,
      AT, and sinus rhythm were used to evaluate the performance of the detectors. All
      patient records with AF (N = 124) were detected by the AF/AT detector to have
      AF/AT burden with a mean, median, and 75 percentile of absolute error in burden
      detection of 8.8, 0, and 4 min, respectively. In patients having AF burden (= or
      > 10 min), the AF/AT detector was found to have burden accuracy within 20% of
      true burden in 96% of patients. The specificity was 94%, defined as follows: in
      patient records without AF/AT (N = 174), the percentage with AF/AT burden = or <
      10 min in the 24-h recordings. The AF/AT detector underestimatesAT burden, thus
      degrading performance, in patients with significant amounts of AT with more
      regular ventricular response. The supplementary AT detector reduces the
      underestimation of AT while overestimating burden in patients without a
      significant amount of AT. The detectors described here could be implemented in an
      implantable monitor for accurate long-term AF/AT monitoring.

PMID- 18334417
TI  - A quantitative method based on total relative change for dynamic electrical
      impedance tomography.
AB  - We proposed a new method based on total relative change (TRC) from measured
      boundary voltages to quantify the volume changes of fluid during electrical
      impedance tomography (EIT) monitoring. The results showed that TRC linearly
      correlated with the volume of infused saline solution into a phantom, and the
      slope of TRC changes was approximately linear with the infusion speed. A inserted
      copper tube at different positions did not affect TRC significantly. The linear
      relationship between TRC and volume change indicates that TRC could be a good
      quantitative index for dynamic EIT.

PMID- 18334418
TI  - Dynamic response of a human head to a foreign object impact.
AB  - This paper presents an analysis of a human head response to impact by a foreign
      object. The analysis is accomplished via an integration of a head-striker contact
      force function with a 3-D finite-element (FE) head model. The contact force
      function developed by the authors is used to estimate the contact force between
      the solid striker and the human head. An explicit FE solver, implemented with the
      contact force function, is employed to predict the human head response to the
      contact impact. The analysis is verified by comparing the present results with
      the experimental data published by others. Based on the present solution, the
      effects of the different impact conditions on the intracranial pressure of the
      head are investigated.

PMID- 18334419
TI  - Automatic classification of asymptomatic and osteoarthritis knee gait patterns
      using kinematic data features and the nearest neighbor classifier.
AB  - The aim of this work is to develop an automatic computer method to distinguish
      between asymptomatic (AS) and osteoarthritis (OA) knee gait patterns using 3-D
      ground reaction force (GRF) measurements. GRF features are first extracted from
      the force vector variations as a function of time and then classified by the
      nearest neighbor rule. We investigated two different features: the coefficients
      of a polynomial expansion and the coefficients of a wavelet decomposition. We
      also analyzed the impact of each GRF component (vertical, anteroposterior, and
      medial lateral) on classification. The best discrimination rate (91%) was
      achieved with the wavelet decomposition using the anteroposterior and the medial
      lateral components. These results demonstrate the validity of the representation
      and the classifier for automatic classification of AS and OA knee gait patterns.
      They also highlight the relevance of the anteroposterior and medial lateral force
      components in gait pattern classification.

PMID- 18334420
TI  - A comparative study of biomechanical simulators in deformable registration of
      brain tumor images.
AB  - Simulating the brain tissue deformation caused by tumor growth has been found to
      aid the deformable registration of brain tumor images. In this paper, we evaluate
      the impact that different biomechanical simulators have on the accuracy of
      deformable registration. We use two alternative frameworks for biomechanical
      simulations of mass effect in 3-D magnetic resonance (MR) brain images. The first
      one is based on a finite-element model of nonlinear elasticity and unstructured
      meshes using the commercial software package ABAQUS. The second one employs
      incremental linear elasticity and regular grids in a fictitious domain method. In
      practice, biomechanical simulations via the second approach may be at least ten
      times faster. Landmarks error and visual examination of the coregistered images
      indicate that the two alternative frameworks for biomechanical simulations lead
      to comparable results of deformable registration. Thus, the computationally less
      expensive biomechanical simulator offers a practical alternative for registration
      purposes.

PMID- 18334421
TI  - Gait simulation via a 6-DOF parallel robot with iterative learning control.
AB  - We have developed a robotic gait simulator (RGS) by leveraging a 6-degree of
      freedom parallel robot, with the goal of overcoming three significant challenges
      of gait simulation, including: 1) operating at near physiologically correct
      velocities; 2) inputting full scale ground reaction forces; and 3) simulating
      motion in all three planes (sagittal, coronal and transverse). The robot will
      eventually be employed with cadaveric specimens, but as a means of exploring the
      capability of the system, we have first used it with a prosthetic foot. Gait data
      were recorded from one transtibial amputee using a motion analysis system and
      force plate. Using the same prosthetic foot as the subject, the RGS accurately
      reproduced the recorded kinematics and kinetics and the appropriate vertical
      ground reaction force was realized with a proportional iterative learning
      controller. After six gait iterations the controller reduced the root mean square
      (RMS) error between the simulated and in situ; vertical ground reaction force to
      35 N during a 1.5 s simulation of the stance phase of gait with a prosthetic
      foot. This paper addresses the design, methodology and validation of the novel
      RGS.

PMID- 18334422
TI  - High-resolution high-speed panoramic cardiac imaging system.
AB  - A panoramic cardiac imaging system consisting of three high-speed CCD cameras has
      been developed to image the surface electrophysiology of a rabbit heart via
      fluorescence imaging using a voltage-sensitive fluorescent dye. A robust, unique
      mechanical system was designed to accommodate the three cameras and to adapt to
      the requirements of future experiments. A unified computer interface was created
      for this application - a single workstation controls all three CCD cameras,
      illumination, stimulation, and a stepping motor that rotates the heart. The
      geometric reconstruction algorithms were adapted from a previous cardiac imaging
      system. We demonstrate the system by imaging a polymorphic cardiac tachycardia.

PMID- 18334423
TI  - Automatic detection and imaging of ischemic changes during electrocardiogram
      monitoring.
AB  - A new electrocardiogram (ECG) monitor with automated ST analysis and display
      capability has been developed to assist healthcare professionals identify the
      site and severity of acute ischemic changes. The monitor displays the changes as
      a 3-D image of the heart in real time. The underpinning assumption is that images
      are easier to interpret than ECG traces. We describe here the features of two
      functions of the monitor, the ischemia detection and imaging function (IF). The
      ischemia detection function was validated using the European ST-T database, and
      was found to have a sensitivity of 85% and positive predictivity of 93%. Fifty
      doctors took part in the evaluation of the new IF and the results showed an
      increase in their median proficiency to diagnose ischemia from 50% to 100% and an
      increase in their certainty of the diagnosis from 65% to 80%. The time to reach a
      diagnosis for eight ECGs, dropped from 15 to 9 min.

PMID- 18334424
TI  - A comparison of two- and four-electrode techniques to characterize blood
      impedance for the frequency range of 100 Hz to 100 MHz.
AB  - Measurement setups that characterize the impedance of suspensions of blood over
      the wide frequency range of 100 Hz to 100 MHz are presented in this paper. The
      performance of the two- and four-electrode techniques have been compared and
      evaluated. By applying a combination of the two measurement techniques the best
      result is achieved when taking into account the main nonidealities, such as
      electrode polarization impedance and parasitic capacitances. It has been found
      that the conventional three-element model for the impedance of blood can be used
      for frequencies up to 1 MHz. For frequencies exceeding 1 MHz, an extended model
      is introduced where a constant phase angle element is used for modeling the cell
      membrane and a capacitor C(liq) is added for modeling the electrical capacitance
      of water in blood.

PMID- 18334425
TI  - Seamless warping of diffusion tensor fields.
AB  - To warp diffusion tensor fields accurately, tensors must be reoriented in the
      space to which the tensors are warped based on both the local deformation field
      and the orientation of the underlying fibers in the original image. Existing
      algorithms for warping tensors typically use forward mapping deformations in an
      attempt to ensure that the local deformations in the warped image remains true to
      the orientation of the underlying fibers; forward mapping, however, can also
      create "seams" or gaps and consequently artifacts in the warped image by failing
      to define accurately the voxels in the template space where the magnitude of the
      deformation is large (e.g., |Jacobian| > 1). Backward mapping, in contrast,
      defines voxels in the template space by mapping them back to locations in the
      original imaging space. Backward mapping allows every voxel in the template space
      to be defined without the creation of seams, including voxels in which the
      deformation is extensive. Backward mapping, however, cannot reorient tensors in
      the template space because information about the directional orientation of fiber
      tracts is contained in the original, unwarped imaging space only, and backward
      mapping alone cannot transfer that information to the template space. To combine
      the advantages of forward and backward mapping, we propose a novel method for the
      spatial normalization of diffusion tensor (DT) fields that uses a bijection (a
      bidirectional mapping with one-to-one correspondences between image spaces) to
      warp DT datasets seamlessly from one imaging space to another. Once the bijection
      has been achieved and tensors have been correctly relocated to the template
      space, we can appropriately reorient tensors in the template space using a
      warping method based on Procrustean estimation.

PMID- 18334426
TI  - Phonovibrography: mapping high-speed movies of vocal fold vibrations into 2-D
      diagrams for visualizing and analyzing the underlying laryngeal dynamics.
AB  - Endoscopic high-speed laryngoscopy in combination with image analysis strategies
      is the most promising approach to investigate the interrelation between vocal
      fold vibrations and voice disorders. So far, due to the lack of an objective and
      standardized analysis procedure a unique characterization of vocal fold
      vibrations has not been achieved yet. We present a visualization and analysis
      strategy which transforms the segmented edges of vibrating vocal folds into a
      single 2-D image, denoted Phonovibrogram (PVG). Within a PVG the individual type
      of vocal fold vibration becomes uniquely characterized by specific geometric
      patterns. The PVG geometries give an intuitive access on the type and degree of
      the laryngeal asymmetry and can be quantified using an image segmentation
      approach. The PVG analysis was applied to 14 representative recordings derived
      from a high-speed database comprising normal and pathological voices. We
      demonstrate that PVGs are capable to differentiate and quantify different types
      of normal and pathological vocal fold vibrations. The objective and precise
      quantification of the PVG geometry may have the potential to realize a novel
      classification of vocal fold vibrations.

PMID- 18334427
TI  - A novel method for the automatic grading of retinal vessel tortuosity.
AB  - Tortuosity is among the first alterations in the retinal vessel network to appear
      in many retinopathies, such as those due to hypertension. An automatic evaluation
      of retinal vessel tortuosity would help the early detection of such
      retinopathies. Quite a few techniques for tortuosity measurement and
      classification have been proposed, but they do not always match the clinical
      concept of tortuosity. This justifies the need for a new definition, able to
      express in mathematical terms the tortuosity as perceived by ophthalmologists. We
      propose here a new algorithm for the evaluation of tortuosity in vessels
      recognized in digital fundus images. It is based on partitioning each vessel in
      segments of constant-sign curvature and then combining together each evaluation
      of such segments and their number. The algorithm has been compared with other
      available tortuosity measures on a set of 30 arteries and one of 30 veins from 60
      different images. These vessels had been preliminarily ordered by a retina
      specialist by increasing perceived tortuosity. The proposed algorithm proved to
      be the best one in matching the clinically perceived vessel tortuosity.

PMID- 18334428
TI  - Analysis of tumor vascularity using three-dimensional power Doppler ultrasound
      images.
AB  - Tumor vascularity is an important factor that has been shown to correlate with
      tumor malignancy and was demonstrated as a prognostic indicator for a wide range
      of cancers. Three-dimensional (3-D) power Doppler ultrasound (PDUS) offers a
      convenient tool for investigators to inspect the signals of blood flow and
      vascular structures in breast cancer. In this paper, a new computer-aided
      diagnosis (CAD) system for quantifying Doppler ultrasound images based on 3-D
      thinning algorithm and neural network is proposed. We extracted the skeleton of
      blood vessels from 3-D PDUS data to facilitate the capturing of morphological
      changes. Nine features including vessel-to-volume ratio, number of vascular
      trees, length of vessels, number of branching, mean of radius, number of cycles,
      and three tortuosity measures, were extracted from the thinning result. Benign
      and malignant tumors can therefore be differentiated by a score computed by a
      multilayered perceptron (MLP) neural network using these features as parameters.
      The proposed system was tested on 221 breast tumors, including 110 benign and 111
      malignant lesions. The accuracy, sensitivity, specificity, and positive and
      negative predictive values were 88.69% (196/221), 91.89% (102/111), 85.45%
      (94/110), 86.44% (102/118), and 91.26% (94/103), respectively. The Az value of
      the ROC curve was 0.94. The results demonstrate a correlation between the
      morphology of blood vessels and tumor malignancy, indicating that the newly
      proposed method can retrieves a high accuracy in the classification of benign and
      malignant breast tumors.

PMID- 18334429
TI  - Multiscale vascular surface model generation from medical imaging data using
      hierarchical features.
AB  - Computational fluid dynamics (CFD) modeling of blood flow from image-based
      patient specific models can provide useful physiologic information for guiding
      clinical decision making. A novel method for the generation of image-based, 3-D,
      multiscale vascular surface models for CFD is presented. The method generates
      multiscale surfaces based on either a linear triangulated or a globally smooth
      nonuniform rational B-spline (NURB) representation. A robust local curvature
      analysis is combined with a novel global feature analysis to set mesh element
      size. The method is particularly useful for CFD modeling of complex vascular
      geometries that have a wide range of vasculature size scales, in conditions where
      1) initial surface mesh density is an important consideration for balancing
      surface accuracy with manageable size volumetric meshes, 2) adaptive mesh
      refinement based on flow features makes an underlying explicit smooth surface
      representation desirable, and 3) semi-automated detection and trimming of a large
      number of inlet and outlet vessels expedites model construction.

PMID- 18334430
TI  - Segmentation of rodent whole-body dynamic PET images: an unsupervised method
      based on voxel dynamics.
AB  - Positron emission tomography (PET) is a useful tool for pharmacokinetics studies
      in rodents during the preclinical phase of drug and tracer development. However,
      rodent organs are small as compared to the scanner's intrinsic resolution and are
      affected by physiological movements. We present a new method for the segmentation
      of rodent whole-body PET images that takes these two difficulties into account by
      estimating the pharmacokinetics far from organ borders. The segmentation method
      proved efficient on whole-body numerical rat phantom simulations, including 3-14
      organs, together with physiological movements (heart beating, breathing, and
      bladder filling). The method was resistant to spillover and physiological
      movements, while other methods failed to obtain a correct segmentation. The
      radioactivity concentrations calculated with this method also showed an excellent
      correlation with the manual delineation of organs in a large set of preclinical
      images. In addition, it was faster, detected more organs, and extracted organs'
      mean time activity curves with a better confidence on the measure than manual
      delineation.

PMID- 18334431
TI  - Intraoperative laparoscope augmentation for port placement and resection planning
      in minimally invasive liver resection.
AB  - In recent years, an increasing number of liver tumor indications were treated by
      minimally invasive laparoscopic resection. Besides the restricted view, two major
      intraoperative issues in laparoscopic liver resection are the optimal planning of
      ports as well as the enhanced visualization of (hidden) vessels, which supply the
      tumorous liver segment and thus need to be divided (e.g., clipped) prior to the
      resection. We propose an intuitive and precise method to plan the placement of
      ports. Preoperatively, self-adhesive fiducials are affixed to the patient's skin
      and a computed tomography (CT) data set is acquired while contrasting the liver
      vessels. Immediately prior to the intervention, the laparoscope is moved around
      these fiducials, which are automatically reconstructed to register the patient to
      its preoperative imaging data set. This enables the simulation of a camera flight
      through the patient's interior along the laparoscope's or instruments' axes to
      easily validate potential ports. Intraoperatively, surgeons need to update their
      surgical planning based on actual patient data after organ deformations mainly
      caused by application of carbon dioxide pneumoperitoneum. Therefore, preoperative
      imaging data can hardly be used. Instead, we propose to use an optically tracked
      mobile C-arm providing cone-beam CT imaging capability intraoperatively. After
      patient positioning, port placement, and carbon dioxide insufflation, the liver
      vessels are contrasted and a 3-D volume is reconstructed during patient
      exhalation. Without any further need for patient registration, the reconstructed
      volume can be directly augmented on the live laparoscope video, since prior
      calibration enables both the volume and the laparoscope to be positioned and
      oriented in the tracking coordinate frame. The augmentation provides the surgeon
      with advanced visual aid for the localization of veins, arteries, and bile ducts
      to be divided or sealed.

PMID- 18334432
TI  - A new method for registration-based medical image interpolation.
AB  - A new technique is presented for interpolating between grey-scale images in a
      medical data set. Registration between neighboring slices is achieved with a
      modified control grid interpolation algorithm that selectively accepts
      displacement field updates in a manner optimized for performance. A cubic
      interpolator is then applied to pixel intensities correlated by the displacement
      fields. Special considerations are made for efficiency, interpolation quality,
      and compression in the implementation of the algorithm. Experimental results show
      that the new method achieves good quality, while offering dramatic improvement in
      efficiency relative to the best competing method.

PMID- 18334433
TI  - A statistical model for point-based target registration error with anisotropic
      fiducial localizer error.
AB  - Error models associated with point-based medical image registration problems were
      first introduced in the late 1990s. The concepts of fiducial localizer error,
      fiducial registration error, and target registration error are commonly used in
      the literature. The model for estimating the target registration error at a
      position r in a coordinate frame defined by a set of fiducial markers rigidly
      fixed relative to one another is ubiquitous in the medical imaging literature.
      The model has also been extended to simulate the target registration error at the
      point of interest in optically tracked tools. However, the model is limited to
      describing the error in situations where the fiducial localizer error is assumed
      to have an isotropic normal distribution in R3. In this work, the model is
      generalized to include a fiducial localizer error that has an anisotropic normal
      distribution. Similar to the previous models, the root mean square statistic rms
      tre is provided along with an extension that provides the covariance Sigma tre.
      The new model is verified using a Monte Carlo simulation and a set of statistical
      hypothesis tests. Finally, the differences between the two assumptions, isotropic
      and anisotropic, are discussed within the context of their use in 1) optical tool
      tracking simulation and 2) image registration.

PMID- 18334434
TI  - Registered 3-D ultrasound and digital stereotactic mammography for breast biopsy
      guidance.
AB  - Large core needle biopsy is a common procedure used to obtain histological
      samples when cancer is suspected in diagnostic breast images. The procedure is
      typically performed under image guidance, with freehand ultrasound and
      stereotactic mammography (SM) being the most common modalities used. To utilize
      the advantages of both modalities, a biopsy device combining three-dimensional
      ultrasound (3DUS) and digital SM imaging with computer-aided needle guidance was
      developed. An implementation of a stereo camera method was applied to SM
      calibration, providing a target localization error of 0.35 mm. The 3-D
      transformation between the two imaging modalities was then derived, with a target
      registration error of 0.52 mm. Finally, the needle guidance error of the device
      was evaluated using tissue-mimicking phantoms, showing a sample mean and standard
      deviation of 0.44 +/- 0.22 and 0.49 +/- 0.27 mm for targets planned from 3DUS and
      SM images, respectively. These results suggest that a biopsy procedure guided
      using this device would successfully sample breast lesions at a size greater than
      or equal to the smallest typically detected in mammographic screening
      (approximately 2 mm).

PMID- 18334435
TI  - An analytical scatter correction for singles-mode transmission data in PET.
AB  - We present an analytical scatter correction, based upon the Klein-Nishina
      formula, for singles-mode transmission data in positron emission tomography (PET)
      and its implementation as part of an iterative image reconstruction algorithm. We
      compared our analytically-calculated scatter sinogram data with previously
      validated simulation data for a small animal PET scanner with 68 Ge (a positron
      emitter) and 57 Co (approximately 122-keV photon emitter) transmission sources
      using four different phantom configurations (three uniform water cylinders with
      radii of 25, 30, and 45 mm and a nonuniform phantom consisting of water, Teflon,
      and air). Our scatter calculation correctly predicts the contribution from single
      scattered (one incoherent scatter interaction) photons to the simulated sinogram
      data and provides good agreement for the percent scatter fraction (SF) per
      sinogram for all phantoms and both transmission sources. We then applied our
      scatter correction as part of an iterative reconstruction algorithm for PET
      transmission data for simulated and experimental data using uniform and
      nonuniform phantoms. For both simulated and experimental data, the reconstructed
      linear attenuation coefficients (mu-values-values) agreed with expected values to
      within 4% when scatter corrections were applied, for both the 68 Ge and 57 Co
      transmission sources. We also tested our reconstruction and scatter correction
      procedure for two experimental rodent studies (a mouse and rat). For the rodent
      studies, we found that the average mu-values for soft-tissue regions of interest
      agreed with expected values to within 4%. Using a 2.2-GHz processor, each scatter
      correction iteration required between 6-27 min of CPU time (without any code
      optimization) depending on the phantom size and source used. This extra
      calculation time does not seem unreasonable considering that, without scatter
      corrections, errors in the reconstructed mu-values were between 18%-45% depending
      on the phantom size and transmission source used.

PMID- 18334436
TI  - Analysis of Resolution and Noise Properties of Nonquadratically Regularized Image
      Reconstruction Methods for PET.
AB  - We present accurate and efficient methods for estimating the spatial resolution
      and noise properties of nonquadratically regularized image reconstruction for
      positron emission tomography (PET). It is well known that quadratic
      regularization tends to over-smooth sharp edges. Many types of edge-preserving
      nonquadratic penalties have been proposed to overcome this problem. However,
      there has been little research on the quantitative analysis of nonquadratic
      regularization due to its nonlinearity. In contrast, quadratically regularized
      estimators are approximately linear and are well understood in terms of
      resolution and variance properties. We derive new approximate expressions for the
      linearized local perturbation response (LLPR) and variance using the Taylor
      expansion with the remainder term. Although the expressions are implicit, we can
      use them to accurately predict resolution and variance for nonquadratic
      regularization where the conventional expressions based on the first-order Taylor
      truncation fail. They also motivate us to extend the use of a certainty-based
      modified penalty to nonquadratic regularization cases in order to achieve
      spatially uniform perturbation responses, analogous to uniform spatial resolution
      in quadratic regularization. Finally, we develop computationally efficient
      methods for predicting resolution and variance of nonquadratically regularized
      reconstruction and present simulations that illustrate the validity of these
      methods.

PMID- 18334437
TI  - 2-D locally regularized tissue strain estimation from radio-frequency ultrasound
      images: theoretical developments and results on experimental data.
AB  - In this paper, a 2-D locally regularized strain estimation method for imaging
      deformation of soft biological tissues from radio-frequency (RF) ultrasound (US)
      data is introduced. Contrary to most 2-D techniques that model the compression
      induced local displacement as a 2-D shift, our algorithm also considers a local
      scaling factor in the axial direction. This direction-dependent model of tissue
      motion and deformation is induced by the highly anisotropic resolution of RF US
      images. Optimal parameters are computed through the constrained maximization of a
      similarity criterion defined as the normalized correlation coefficient. Its value
      at the solution is then used as an indicator of estimation reliability, the
      probability of correct estimation increasing with the correlation value. In case
      of correlation loss, the estimation integrates an additional constraint, imposing
      local continuity within displacement and strain fields. Using local scaling
      factors and regularization increase the method's robustness with regard to
      decorrelation noise, resulting in a wider range of precise measurements. Results
      on simulated US data from a mechanically homogeneous medium subjected to
      successive uniaxial loadings demonstrate that our method is theoretically able to
      accurately estimate strains up to 17%. Experimental strain images of phantom and
      cut specimens of bovine liver clearly show the harder inclusions.

PMID- 18334438
TI  - A surface-based approach to quantify local cortical gyrification.
AB  - The high complexity of cortical convolutions in humans is very challenging both
      for engineers to measure and compare it, and for biologists and physicians to
      understand it. In this paper, we propose a surface-based method for the
      quantification of cortical gyrification. Our method uses accurate 3-D cortical
      reconstruction and computes local measurements of gyrification at thousands of
      points over the whole cortical surface. The potential of our method to identify
      and localize precisely gyral abnormalities is illustrated by a clinical study on
      a group of children affected by 22q11 Deletion Syndrome, compared to control
      individuals.

PMID- 18334439
TI  - A robust and accurate two-stage approach for automatic recovery of distal locking
      holes in computer-assisted intramedullary nailing of femoral shaft fractures.
AB  - It has been recognized that one of the most difficult steps in intramedullary
      nailing of femoral shaft fractures is the distal locking - the insertion of
      distal transverse interlocking screws, for which it is necessary to know the
      positions and orientations of the distal locking holes (DLHs) of the
      intramedullary nail (IMN). This paper presents a robust and accurate approach for
      solving this problem based on two calibrated and registered fluoroscopic images.
      The problem is formulated as a two-stage model-based optimal fitting process. The
      first stage, nail detection, automatically estimates the axis of the distal part
      of the IMN (DP-IMN) by iteratively fitting a cylindrical model to the images. The
      second stage, pose recovery, resolves the translations and the rotations of the
      DLHs around the estimated axis by iteratively fitting the geometrical models of
      the DLHs to the images. An iterative best matched projection point (IBMPP)
      algorithm is combined with random sample strategies to effectively and robustly
      solve the fitting problems in both stages. We designed and conducted
      comprehensive experiments to validate the robustness and the accuracy of the
      present approach. Our in vitro experiments show on average less than 14 s
      execution time on a Linux machine, a mean angular error of 0.48 degrees (std =
      0.21 degrees ), and a mean translational error of 0.09 mm (std = 0.041 mm). We
      conclude that the present approach is fast, robust, and accurate for distal
      locking applications.

PMID- 18334440
TI  - Surface Reconstruction for free-space 360 degrees fluorescence molecular
      tomography and the effects of animal motion.
AB  - Complete projection (360 degrees ) free-space fluorescence tomography of opaque
      media is poised to enable 3-D imaging through entire small animals in vivo with
      improved depth resolution compared to 360 degrees -projection fiber-based systems
      or limited-view angle systems. This approach can lead to a new generation of
      Fluorescence Molecular Tomography (FMT) performance since it allows high spatial
      sampling of photon fields propagating through tissue at any projection, employing
      nonconstricted animal surfaces. Herein, we employ a volume carving method to
      capture 3-D surfaces of diffusive objects and register the captured surface in
      the geometry of an FMT 360 degrees -projection acquisition system to obtain 3-D
      fluorescence image reconstructions. Using experimental measurements we evaluate
      the accuracy of the surface capture procedure by reconstructing the surfaces of
      phantoms of known dimensions. We then employ this methodology to characterize the
      animal movement of anaesthetized animals. We find that the effects of animal
      movement on the FMT reconstructed image were within system resolution limits
      (approximately 0.07 cm).

PMID- 18334441
TI  - Segmentation of the left ventricle of the heart in 3-D+t MRI data using an
      optimized nonrigid temporal model.
AB  - Modern medical imaging modalities provide large amounts of information in both
      the spatial and temporal domains and the incorporation of this information in a
      coherent algorithmic framework is a significant challenge. In this paper, we
      present a novel and intuitive approach to combine 3-D spatial and temporal (3-D +
      time) magnetic resonance imaging (MRI) data in an integrated segmentation
      algorithm to extract the myocardium of the left ventricle. A novel level-set
      segmentation process is developed that simultaneously delineates and tracks the
      boundaries of the left ventricle muscle. By encoding prior knowledge about
      cardiac temporal evolution in a parametric framework, an expectation-maximization
      algorithm optimally tracks the myocardial deformation over the cardiac cycle. The
      expectation step deforms the level-set function while the maximization step
      updates the prior temporal model parameters to perform the segmentation in a
      nonrigid sense.

PMID- 18334442
TI  - Perturbative refinement of the geometric calibration in pinhole SPECT.
AB  - The paper investigates the geometric calibration of a rotating gamma camera for
      pinhole (PH) single photon emission computed tomography (SPECT) imaging. Most
      calibration methods previously applied in PH-SPECT assume that the motion of the
      camera around the object belongs to a well-defined class described by a small
      number of geometric parameters, for instance seven parameters for a circular
      acquisition with a single pinhole camera. The proposed new method refines an
      initial parametric calibration by applying to each position of the camera a rigid
      body transformation that is determined to improve the fit between the measured
      and calculated projections of the calibration sources. A stable estimate of this
      transformation can be obtained with only three calibration sources by linearizing
      the equations around the position estimated by the initial parametric
      calibration. The performance of the method is illustrated using simulated and
      measured micro-SPECT data.

PMID- 18334443
TI  - Performance analysis of three-class classifiers: properties of a 3-D ROC surface
      and the normalized volume under the surface for the ideal observer.
AB  - Classification of a given observation to one of three classes is an important
      task in many decision processes or pattern recognition applications. A general
      analysis of the performance of three-class classifiers results in a complex 6-D
      receiver operating characteristic (ROC) space, for which no simple analytical
      tool exists at present. We investigate the performance of an ideal observer under
      a specific set of assumptions that reduces the 6-D ROC space to 3-D by
      constraining the utilities of some of the decisions in the classification task.
      These assumptions lead to a 3-D ROC space in which the true-positive fraction
      (TPF) can be expressed in terms of the two types of false-positive fractions
      (FPFs). We demonstrate that the TPF is uniquely determined by, and therefore is a
      function of, the two FPFs. The domain of this function is shown to be related to
      the decision boundaries in the likelihood ratio plane. Based on these properties
      of the 3-D ROC space, we can define a summary measure, referred to as the
      normalized volume under the surface (NVUS), that is analogous to the area under
      the ROC curve (AUC) for a two-class classifier. We further investigate the
      properties of the 3-D ROC surface and the NVUS for the ideal observer under the
      condition that the three class distributions are multivariate normal with equal
      covariance matrices. The probability density functions (pdfs) of the decision
      variables are shown to follow a bivariate log-normal distribution. By considering
      these pdfs, we express the TPF in terms of the FPFs, and integrate the TPF over
      its domain numerically to obtain the NVUS. In addition, we performed a Monte
      Carlo simulation study, in which the 3-D ROC surface was generated by empirical
      "optimal" classification of case samples in the multidimensional feature space
      following the assumed distributions, to obtain an independent estimate of NVUS.
      The NVUS value obtained by using the analytical pdfs was found to be in good
      agreemen- t with that obtained from the Monte Carlo simulation study. We also
      found that, under all conditions studied, the NVUS increased when the difficulty
      of the classification task was reduced by changing the parameters of the class
      distributions, thereby exhibiting the properties of a performance metric in
      analogous to AUC. Our results indicate that, under the conditions that lead to
      our 3-D ROC analysis, the performance of a three-class classifier may be analyzed
      by considering the ROC surface, and its accuracy characterized by the NVUS.

PMID- 18334444
TI  - Selecting and assessing quantitative early ultrasound texture measures for their
      association with cerebral palsy.
AB  - Cerebral palsy (CP) develops as a consequence of white matter damage (WMD) in
      approximately one out of every 10 very preterm infants. Ultrasound (US) is widely
      used to screen for a variety of brain injuries in this patient population, but
      early US often fails to detect WMD. We hypothesized that quantitative texture
      measures on US images obtained within one week of birth are associated with the
      subsequent development of CP. In this retrospective study, using images from a
      variety of US machines, we extracted unique texture measures by means of adaptive
      processing and high resolution feature enhancement. We did not standardize the
      images, but used patients as their own controls. We did not remove speckle, as it
      may contain information. To test our hypothesis, we used the "random forest"
      algorithm to create a model. The random forest classifier achieved a 72% match to
      the health outcome of the patients (CP versus no CP), whereas designating all
      patients as having CP would have resulted in 53% error. This suggests that
      quantitative early texture measures contain diagnostic information relevant to
      the development of CP.

PMID- 18334445
TI  - A novel vessel segmentation algorithm for pathological retina images based on the
      divergence of vector fields.
AB  - In this paper, a method is proposed for detecting blood vessels in pathological
      retina images. In the proposed method, blood vessel-like objects are extracted
      using the Laplacian operator and noisy objects are pruned according to the
      centerlines, which are detected using the normalized gradient vector field. The
      method has been tested with all the pathological retina images in the publicly
      available STARE database. Experiment results show that the method can avoid
      detecting false vessels in pathological regions and can produce reliable results
      for healthy regions.

PMID- 18334446
TI  - Simultaneous ultrasound and MRI system for breast biopsy: compatibility
      assessment and demonstration in a dual modality phantom.
AB  - Simultaneous capturing of ultrasound (US) and magnetic resonance (MR) images
      allows fusion of information obtained from both modalities. We propose an MR
      compatible US system where MR images are acquired in a known orientation with
      respect to the US imaging plane and concurrent real-time imaging can be achieved.
      Compatibility of the two imaging devices is a major issue in the physical setup.
      Tests were performed to quantify the radio frequency (RF) noise introduced in MR
      and US images, with the US system used in conjunction with MRI scanner of
      different field strengths (0.5 T and 3 T). Furthermore, simultaneous imaging was
      performed on a dual modality breast phantom in the 0.5 T open bore and 3 T close
      bore MRI systems to aid needle-guided breast biopsy. Fiducial based passive
      tracking and electromagnetic based active tracking were used in 3 T and 0.5 T,
      respectively, to establish the location and orientation of the US probe inside
      the magnet bore. Our results indicate that simultaneous US and MR imaging are
      feasible with properly-designed shielding, resulting in negligible broadband
      noise and minimal periodic RF noise in both modalities. US can be used for real
      time display of the needle trajectory, while MRI can be used to confirm needle
      placement.

PMID- 18334447
TI  - Intraoperative magnetic tracker calibration using a magneto-optic hybrid tracker
      for 3-D ultrasound-based navigation in laparoscopic surgery.
AB  - This paper describes a ultrasound (3-D US) system that aims to achieve augmented
      reality (AR) visualization during laparoscopic surgery, especially for the liver.
      To acquire 3-D US data of the liver, the tip of a laparoscopic ultrasound probe
      is tracked inside the abdominal cavity using a magnetic tracker. The accuracy of
      magnetic trackers, however, is greatly affected by magnetic field distortion that
      results from the close proximity of metal objects and electronic equipment, which
      is usually unavoidable in the operating room. In this paper, we describe a
      calibration method for intraoperative magnetic distortion that can be applied to
      laparoscopic 3-D US data acquisition; we evaluate the accuracy and feasibility of
      the method by in vitro and in vivo experiments. Although calibration data can be
      acquired freehand using a magneto-optic hybrid tracker, there are two problems
      associated with this method--error caused by the time delay between measurements
      of the optical and magnetic trackers, and instability of the calibration accuracy
      that results from the uniformity and density of calibration data. A temporal
      calibration procedure is developed to estimate the time delay, which is then
      integrated into the calibration, and a distortion model is formulated by zeroth
      degree to fourth-degree polynomial fitting to the calibration data. In the in
      vivo experiment using a pig, the positional error caused by magnetic distortion
      was reduced from 44.1 to 2.9 mm. The standard deviation of corrected target
      positions was less than 1.0 mm. Freehand acquisition of calibration data was
      performed smoothly using a magneto-optic hybrid sampling tool through a trocar
      under guidance by realtime 3-D monitoring of the tool trajectory; data
      acquisition time was less than 2 min. The present study suggests that our
      proposed method could correct for magnetic field distortion inside the patient's
      abdomen during a laparoscopic procedure within a clinically permissible period of
      time, as well as enabling an accurate 3-D US reconstruction to be obtained that
      can be superimposed onto live endoscopic images.

PMID- 18334448
TI  - A fast nonrigid image registration with constraints on the Jacobian using large
      scale constrained optimization.
AB  - This paper presents a new nonrigid monomodality image registration algorithm
      based on B-splines. The deformation is described by a cubic B-spline field and
      found by minimizing the energy between a reference image and a deformed version
      of a floating image. To penalize noninvertible transformation, we propose two
      different constraints on the Jacobian of the transformation and its derivatives.
      The problem is modeled by an inequality constrained optimization problem which is
      efficiently solved by a combination of the multipliers method and the L-BFGS
      algorithm to handle the large number of variables and constraints of the
      registration of 3-D images. Numerical experiments are presented on magnetic
      resonance images using synthetic deformations and atlas based segmentation.

PMID- 18334449
TI  - In vitro analysis of cisplatin functionalized magnetic nanoparticles in combined
      cancer chemotherapy and electromagnetic hyperthermia.
AB  - A novel platform has been developed for combined cancer chemotherapy and
      hyperthermia based on iron oxide magnetic nanoparticles functionalized with cis
      diamminedichloroplatinum(II) (cisplatin). The capabilities of this system for
      heating and controlled drug release were investigated, and the system was tested
      in vitro by the treatment of BP6 rat sarcoma cells, where we demonstrated a
      synergism between the effects of cisplatin-targetMAG nanoparticles and the
      application of electromagnetic field.

PMID- 18334450
TI  - FIB-nanostructured surfaces and investigation of Bio/nonbio interactions at the
      nanoscale.
AB  - A better understanding of the interactions between biological entities and
      nanostructures is of central importance for developing functionalized materials
      and systems such as active surfaces with adapted biocompatibility. There is clear
      evidence in literature that cells and proteins generally interact with nanoscale
      featured surfaces. Despite this quantity of information, little is known about
      the functional relationship between surface properties (i.e., roughness and
      nanostructuration) and biomolecules interaction. The main obstacle in the
      achievement of this goal is a technological one. Precise and straightforward
      control on surface modification at the nanometer level is required for
      understanding how nanostructuration influences interactions at bio/nonbio
      interface. In this paper, the authors describe the advantages of the focused ion
      beam (FIB) for surface nanostructuration of any material. The use of light
      transmitting substrates (especially glass) is often useful when studying the
      influence of surface morphology-in terms of shape and feature size-on bio/nonbio
      interactions by using traditional methods of biology and biotechnology. A simple
      methodology enabling a very efficient patterning of glass surfaces is thus
      described and validated: the enhancement of proteins interaction on FIB
      nanostructured glass surfaces is demonstrated via fluorescence assays and a
      relationship between the adsorbed protein concentration and the density of
      surface patterning is derived.

PMID- 18334451
TI  - Carbon nanotube fibers are compatible with Mammalian cells and neurons.
AB  - We demonstrate the biocompatibility of carbon nanotube fibers (CNFs) fabricated
      from single-wall carbon nanotubes. Produced by a particle-coagulation spinning
      process, CNFs are "hair-like" conductive microwires, which uniquely combine
      properties of porous nanostructured scaffolds, high-area electrodes, and
      permeable microfluidic conduits. We report that CNFs are nontoxic and support the
      attachment, spreading, and growth of mammalian cells and the extension of
      processes from neurons in vitro. Our findings suggest that CNF may be employed
      for an electrical interfacing of nerve cells and external devices.

PMID- 18334452
TI  - Construction and evaluation of an automated light directed protein-detecting
      microarray synthesizer.
AB  - We have designed, constructed, and evaluated an automated instrument that has
      produced high-density arrays with more than 30 000 peptide features within a 1.5
      cm(2) area of a glass slide surface. These arrays can be used for high throughput
      library screening for protein binding ligands, for potential drug candidate
      molecules, or for discovering biomarkers. The device consists of a novel fluidics
      system, a relay control electrical system, an optics system that implements Texas
      Instruments' digital micromirror device (DMD), and a microwave source for
      accelerated synthesis of peptide arrays. The instrument implements two novel
      solid phase chemical synthesis strategies for producing peptide and peptoid
      arrays. Biotin-streptavidin and DNP anti-DNP (dinitrophenol) models of antibody
      small molecule interactions were used to demonstrate and evaluate the
      instrument's capability to produce high-density protein detecting arrays. Several
      screening assay and detection schemes were explored with various levels of
      efficiency and assays with sensitivity of 10 nM were also possible.

PMID- 18334453
TI  - Functionalized solid lipid nanoparticles for transendothelial delivery.
AB  - The objectives of this study were to synthesize and characterize functionalized
      solid lipid nanoparticles (fSLN) to investigate their interaction with
      endothelial cell monolayers and to evaluate their transendothelial transport
      capabilities. fSLN bearing tetramethylrhodamine-isothiocyanate-labeled bovine
      serum albumin (TRITC-BSA) and Coumarin 6 were prepared using a single-step phase
      inversion process that afforded concurrent surface modification with a variety of
      macromolecules such as polystyrene sulfonate (PSS), poly-L-lysine (PLL), heparin
      (Hep), polyacrylic acid (PAA), polyvinyl alcohol, and polyethylene glycol (PEG).
      TRITC-BSA/Coumarin 6 encapsulated in fSLN with composite surface functionality
      (PSS-PLL and PSS-PLL-Hep) were also investigated. Size and surface charge of fSLN
      were analyzed using dynamic light scattering and transmission electron
      microscopy. Transport across bovine aortic endothelial cell (BAEC) monolayers was
      assessed spectrophotometrically using a transwell assay, and fSLN localization at
      the level of the cell and permeable support was analyzed using fluorescence
      microscopy. fSLN with tunable size and surface functionality were successfully
      produced, and had significant effects on cell localization and transport.
      Specifically, fSLN with PSS-PLL-Hep composite surface functionalization was
      capable of translocating 53.2 +/- 8.7 mug of TRITC-BSA within 4 h, with fSLN-PEG,
      fSLN-PAA, and fSLN-PSS exhibiting near-complete apical, paracellular, and
      cytosolic localization, respectively. Coumarin 6 was released by fSLN as
      indicated by dye labeling of BAEC membranes. We have developed a rapid process
      for the production of fSLN bearing low- and high-molecular-weight payloads of
      varying physicochemical properties. These findings have impications for drug
      delivery and bioimaging applications, since due to tunable surface chemistry,
      fSLN internalization and/or translocation across intact endothelial cell
      monolayers is possible.

PMID- 18334454
TI  - Distributed sequence alignment applications for the public computing
      architecture.
AB  - The public computer architecture shows promise as a platform for solving
      fundamental problems in bioinformatics such as global gene sequence alignment and
      data mining with tools such as the basic local alignment search tool (BLAST). Our
      implementation of these two problems on the Berkeley open infrastructure for
      network computing (BOINC) platform demonstrates a runtime reduction factor of
      1.15 for sequence alignment and 16.76 for BLAST. While the runtime reduction
      factor of the global gene sequence alignment application is modest, this value is
      based on a theoretical sequential runtime extrapolated from the calculation of a
      smaller problem. Because this runtime is extrapolated from running the
      calculation in memory, the theoretical sequential runtime would require 37.3 GB
      of memory on a single system. With this in mind, the BOINC implementation not
      only offers the reduced runtime, but also the aggregation of the available memory
      of all participant nodes. If an actual sequential run of the problem were
      compared, a more drastic reduction in the runtime would be seen due to an
      additional secondary storage I/O overhead for a practical system. Despite the
      limitations of the public computer architecture, most notably in communication
      overhead, it represents a practical platform for grid- and cluster-scale
      bioinformatics computations today and shows great potential for future
      implementations.

PMID- 18334455
TI  - Stochastic dynamic modeling of short gene expression time-series data.
AB  - In this paper, the expectation maximization (EM) algorithm is applied for
      modeling the gene regulatory network from gene time-series data. The gene
      regulatory network is viewed as a stochastic dynamic model, which consists of the
      noisy gene measurement from microarray and the gene regulation first-order
      autoregressive (AR) stochastic dynamic process. By using the EM algorithm, both
      the model parameters and the actual values of the gene expression levels can be
      identified simultaneously. Moreover, the algorithm can deal with the sparse
      parameter identification and the noisy data in an efficient way. It is also shown
      that the EM algorithm can handle the microarrary gene expression data with large
      number of variables but a small number of observations. The gene expression
      stochastic dynamic models for four real-world gene expression data sets are
      constructed to demonstrate the advantages of the introduced algorithm. Several
      indices are proposed to evaluate the models of inferred gene regulatory networks,
      and the relevant biological properties are discussed.

PMID- 18334456
TI  - Error tolerant DNA self-assembly using (2k - 1)x(2k - 1) snake tile sets.
AB  - DNA self-assembly has been advocated as a possible technique for bottom-up
      manufacturing of scaffolds for computing systems in the nanoscale region.
      However, self-assembly is affected by different types of errors (such as growth
      and facet roughening) that severely limit its applicability. Different methods
      for reducing the error rate of self-assembly using tiles as basic elements have
      been proposed. A particularly effective method relies on snake tile sets that
      utilize a square block of even size (i.e., 2k x 2k tiles, k = 2, 3, . . .). In
      this paper, an odd-sized square block [i.e., (2k - 1) x (2k - 1)] is proposed as
      basis for the snake tile set. Compared with other tile sets, the proposed snake
      tile sets achieve a considerable reduction in error rate at a very modest
      reduction in growth rate. Growth and facet roughening errors are considered and
      analytical results are presented to prove the reduction in error rate compared
      with an even-sized snake tile set. Simulation results are provided.

PMID- 18334457
TI  - Investigation of self-organizing oscillator networks for use in clustering
      microarray data.
AB  - The self-organizing oscillator network (SOON) is a comparatively new clustering
      algorithm that does not require the knowledge of the number of clusters. The SOON
      is distance based, and its clustering behavior is different to density-based
      algorithms in a number of ways. This paper examines the effect of adjusting the
      control parameters of the SOON with four different datasets; the first is a
      (communications) modulation dataset representing one modulation scheme under a
      variety of noise conditions. This allows the assessment of the behavior of the
      algorithm with data varying between highly separable and nonseparable cases. The
      main thrust of this paper is to evaluate its efficacy in biological datasets. The
      second is taken from microarray experiments on the cell cycle of yeast, while the
      third and the fourth represent two microarray cancer datasets, i.e., the lymphoma
      and the liver cancer datasets. The paper demonstrates that the SOON is a viable
      tool to analyze these problems, and can add many useful insights to the
      biological data that may not always be available using other clustering methods.

PMID- 18334458
TI  - Correlations between the experimental and numerical investigations on the
      mechanical properties of erythrocyte by laser stretching.
AB  - The deformation and mechanical properties of the erythrocytes are studied
      experimentally and numerically. For the experimental part, an osmotic swollen
      spherical erythrocyte was attached with a pair of silica beads, and then
      stretched at two opposite ends by a laser trap. The purpose of this experiment is
      to find the empirical correlation between the stretching force and the cell
      deformation in terms of the transverse strain, which is a measure of the change
      of radius in a spherical cell along its equator. Experimental results show the
      cell shape become more oblate, elliptic as the stretching force increases. On the
      numerical front, a physical model from the original work by Pamplona and
      Calladine for the lipsomes was extended to simulate the deformation of the cell
      membrane. Numerical analyses were performed to solve the nondimensionalized
      governing equations with proper boundary conditions imposed to simulate the
      experimental conditions. The simulated results indicate that at high tensile
      stiffness, the cell can deform into a spindle shape with negative curvature close
      to the ends of stretch. Finally, the experimental data and the simulated results
      were correlated through optimization by minimizing their discrepancy at various
      values of the shear stiffness. The optimal value of shear stiffness was found in
      the range of 2.35 approximately 4.29 10(-6) N.m(-1), which is comparable with
      those values reported in the literature.

PMID- 18334459
TI  - A combination of rough-based feature selection and RBF neural network for
      classification using gene expression data.
AB  - This paper presents a novel rough-based feature selection method for gene
      expression data analysis. It can find the relevant features without requiring the
      number of clusters to be known a priori and identify the centers that approximate
      to the correct ones. In this paper, we attempt to introduce a prediction scheme
      that combines the rough-based feature selection method with radial basis function
      neural network. For further consider the effect of different feature selection
      methods and classifiers on this prediction process, we use the NaIve Bayes and
      linear support vector machine as classifiers, and compare the performance with
      other feature selection methods, including information gain and principle
      component analysis. We demonstrate the performance by several published datasets
      and the results show that our proposed method can achieve high classification
      accuracy rate.

PMID- 18334461
TI  - Prospective evaluation of occlusive hydrocolloid dressing versus conventional
      gauze dressing regarding the healing effect after abdominal operations:
      randomized controlled trial.
AB  - OBJECTIVE: To compare occlusive hydrocolloid dressing (OHD; Karayahesive) and
      gauze dressing (GD) with regard to the cost and incidence of wound infection
      after abdominal surgery. METHODS: A total of 134 patients who underwent incisions
      were randomized to have their wounds dressed with either OHD or GD. OHD was left
      on until the sutures were removed, and GD was changed everyday postoperatively.
      The cost calculations represent the number of dressings required for each
      treatment group as determined by the frequency of required dressing changes and
      cost per dressing. RESULTS: There were no differences between the groups
      regarding the need for dressings to be changed or the incidence of infection. OHD
      was less expensive and complicated than GD, which needed to be changed everyday
      (p < 0.0001). CONCLUSION: The results suggest that OHD is less expensive to use
      than GD, and the risk of wound infection is not increased compared to GD.

PMID- 18334462
TI  - Laparoscopic intragastric approach for stromal tumours located at the posterior
      gastric wall.
AB  - Surgical resection is indicated for gastrointestinal stromal tumour (GIST).
      Laparoscopic resection with clear margins is effective in gastric GIST. However,
      GIST located in the posterior gastric wall with close proximity to the
      oesophagogastric junction poses special challenges. Laparoscopic intragastric
      resection offers a new approach to the management of these tumours. The surgical
      technique, our experience and a summary of the literature are presented.

PMID- 18334463
TI  - Serum lipoprotein(a) levels in patients with atherosclerotic peripheral vascular
      disease in Hospital Kuala Lumpur.
AB  - OBJECTIVE: The objective of this study was to determine the proportion of
      patients with atherosclerotic peripheral vascular disease (PVD) who had elevated
      lipoprotein(a) [Lp(a)] levels, as well as to determine the latter's significance
      as a risk factor for PVD in the local population. METHODS: This case-controlled
      study was conducted between June and October 2004 in the Department of Surgery,
      Kuala Lumpur Hospital. A total of 100 patients were recruited and divided into
      control and PVD groups. Patients were defined as having PVD if they were
      symptomatic, with ankle-brachial systolic index < 0.90, or by radiological
      evidence. Lp(a) concentrations were determined using immunoturbidometry.
      Absorbance of reaction precipitate was measured by spectrophotometry to give
      Lp(a) concentration in grams per litre (g/L). The reference value for normal
      Lp(a) levels was < or = 0.36 g/L. RESULTS: Mean Lp(a) levels for control and PVD
      groups were 0.29 g/L and 0.56 g/L, and median values were 0.17 g/L and 0.48 g/L,
      respectively. Elevated Lp(a) levels in the control group was 26% compared to 58%
      in the PVD group. Analysis with Pearson's chi-squared test achieved a significant
      p value of 0.001. Multivariate analysis showed that elevated Lp(a) levels
      contributed significantly to the probability of having PVD with an odds ratio of
      7.69. CONCLUSION: Elevated serum Lp(a) has a significant role as a risk factor
      for atherosclerotic PVD in the local population.

PMID- 18334464
TI  - Role of colour Doppler imaging in detecting prostate cancer.
AB  - OBJECTIVE: This prospective study was undertaken to evaluate the role of colour
      Doppler sonography in the assessment of prostate carcinoma. METHODS: Forty
      consecutive patients who were suspected of having prostate carcinoma with either
      raised prostate specific antigen or abnormal digital rectal examination were
      included in the study. Transrectal greyscale and colour Doppler sonography of the
      prostate was performed using a 5-9 MHz intracavitary probe. Needle biopsies were
      taken from areas that showed increased flow on colour Doppler. The results were
      correlated with the final diagnosis established on histopathological examination.
      RESULTS: Comparison of greyscale and colour Doppler sonography showed that the
      latter is more sensitive and specific in predicting the malignancy. The
      statistical parameters of colour Doppler versus grayscale sonography were:
      sensitivity 88.23 vs. 73.52, specificity 66.66 vs. 33.33, positive predictive
      value 93.75 vs. 85.18, and negative predictive value 50 vs. 22.22, respectively.
      CONCLUSION: Colour Doppler and greyscale sonography should be routinely performed
      to improve detection of prostate carcinoma and to target the lesion.

PMID- 18334465
TI  - Prognostic factors for upper tract transitional cell carcinoma: a retrospective
      review of 66 patients.
AB  - OBJECTIVE: We assessed the prognostic factors on recurrence and disease-specific
      survival of patients treated for upper tract transitional cell carcinoma (TCC).
      METHODS: Data on 66 patients who were treated for upper tract TCC in a single
      centre over a 13-year period were analysed. Mean follow-up time was 49.2 months.
      Fifty-five out of 66 (83.3%) underwent nephroureterectomy with excision of a
      bladder cuff. Four (6.1%) patients had nephrectomy alone while three (4.5%) had
      renal-sparing surgery. Four patients did not receive surgery due to advanced age
      and other comorbidities. Age, sex, tumour location, stage and grade were analysed
      as prognostic factors for disease recurrence and disease-specific survival using
      log rank univariate analysis. RESULTS: Disease recurrence occurred in 45 (68.2%)
      patients at a median time of 11.0 months. Recurrences were found in the bladder
      in 27.3%, the contralateral renal pelvis in 4.5%, local retroperitoneum in 19.7%,
      distant sites in 13.6%, with simultaneous local and distant metastases occurring
      in 3.0%. Tumour stage was the only significant prognostic factor for recurrence.
      Presence of extraurothelial recurrence, stage and grade were significant
      prognostic factors for disease-specific survival. CONCLUSION: Tumour stage was
      the most consistent predictor of both disease recurrence and survival. These
      findings would guide the need for any adjuvant chemoradiotherapy.

PMID- 18334466
TI  - Inflammatory myofibroblastic tumours of the spleen and liver.
AB  - Inflammatory myofibroblastic tumour (IMT) is a rare neoplasm. Generally, these
      lesions have a benign behaviour, but the possibility of malignant transformation
      exists. We report the rare case of a 43-year-old woman with metachronous IMTs in
      the spleen and the liver. The patient was treated with laparoscopic splenectomy
      and partial hepatectomy. The patient recovered uneventfully. This case emphasizes
      the difficulties in diagnosis and the possibility of a metachronous occurrence.

PMID- 18334467
TI  - Pleurobiliary fistula secondary to choledocholithiasis --- a rare entity.
AB  - Pleurobiliary fistula secondary to common bile duct obstruction due to stone is a
      very rare clinical entity. A 55-year-old female patient presented in the
      emergency department with features of septicaemia with left pleural effusion.
      Intercostal tube drainage drained 5 L of bile on the first day and around 500-600
      mL of bile each day subsequently. Magnetic resonance cholangiopancreaticography
      showed choledocholithiasis with pleurobiliary fistula. The patient underwent
      bilioenteric bypass and ligation of the fistulous tract with complete cure.

PMID- 18334468
TI  - Unusual cause of acute abdomen --- ruptured retroperitoneal paraganglioma.
AB  - Ruptured retroperitoneal paraganglioma is a rare cause of acute abdomen. Its
      clinical presentation and laparoscopic features have seldom been reported in the
      literature. Herein, we report a case of ruptured retroperitoneal paraganglioma
      that presented as acute abdomen, and its subsequent management.

PMID- 18334469
TI  - Transcatheter arterial embolization of spontaneous rectus sheath haematoma in a
      Chinese woman.
AB  - Spontaneous extraperitoneal haemorrhage is a rare but well-described complication
      of anticoagulation therapy. We report a case of spontaneous rectus sheath
      haematoma in a 69-year-old Chinese woman who had received low-molecular-weight
      heparin for pulmonary embolism. She presented with sudden onset of lower
      abdominal pain, hypotension and a tender lower abdominal mass after 1 week of
      anticoagulation therapy. Computed tomography revealed a huge right rectus sheath
      haematoma extending into the pelvis, and angiography demonstrated active contrast
      extravasation from the right inferior epigastric artery. Arterial embolization
      with Gelfoam was performed and succeeded in stopping the bleeding. Transcatheter
      arterial embolization can be an effective and safe modality to localize and treat
      the bleeder in spontaneous extraperitoneal haematoma for high-risk patients.

PMID- 18334470
TI  - Notice of retraction of "Effect of four crystalloid cardioplegias on immature
      rabbit hearts during global ischemia", Asian J Surg 2006;29(2):79-85.

PMID- 18334471
TI  - Ultrasound imaging techniques for the evaluation of cardiovascular therapies.
AB  - Cardiovascular disease remains a substantial cause of morbidity and mortality in
      the developed world, and is becoming an increasingly important cause of death in
      developing countries too. While current cardiovascular treatments can help to
      reduce this disease burden, a substantial number of patients still retain a high
      risk of experiencing a life-threatening cardiovascular event. Thus, the
      development of new therapies capable of reducing this residual risk remains an
      important healthcare objective. The time taken to bring new therapies to the
      patient in need is lengthened by the unavoidable requirement to demonstrate a
      statistically significant benefit in terms of clinical events beyond that
      achievable with current treatments. However, clinical trials utilizing surrogate
      endpoints-biomarkers of disease progression that manifest before potentially
      fatal cardiovascular events occur-have the potential to enhance the process of
      drug development by enabling a statistically sound assessment of the efficacy of
      new therapies several years in advance of the availability of data from clinical
      endpoint trials. Two vascular ultrasound imaging techniques, measurement of
      carotid intima-media thickness (CIMT) and intravascular ultrasound (IVUS) of the
      coronary arteries, are increasingly being used to assess novel cardiovascular
      therapies in surrogate endpoint trials forming integral components of larger
      trial programmes utilizing both surrogate and clinical endpoints. The rationale
      for the use of CIMT- and IVUS-based surrogates, with supporting evidence from
      historical and recent trials, is presented in this review article.

PMID- 18334472
TI  - Developing the utility of blood biomarker associations beyond population sample
      linkage to events in cardiovascular patients.

PMID- 18334473
TI  - Variation in the use of stress testing and outcomes in patients with non-ST
      elevation acute coronary syndromes: insights from GUSTO IIb.
AB  - AIMS: Non-invasive risk stratification of low- and intermediate-risk non-ST
      elevation acute coronary syndromes (NSTE ACS) patients has been recommended, but
      limited data exist about the variation in clinical practice of stress testing in
      these patients and the impact of such testing on their outcomes. METHODS AND
      RESULTS: Patients with NSTE ACS enrolled in the GUSTO IIb (Global Use of
      Strategies To Open occluded coronary arteries in acute coronary syndromes-IIb)
      trial (n = 8011) were analysed to evaluate patterns of stress testing in US and
      non-US patients and to further evaluate the clinical characteristics, procedure
      use, and outcomes of patients who underwent stress testing compared with those
      who did not. Stress testing was performed in 1878 (24%) patients. Compared with
      patients not undergoing stress testing, those undergoing stress testing had low
      risk characteristics and significantly lower death (0.6% vs. 4.8%), and death or
      myocardial infarction (MI, 3.9% vs. 11%) rates at 30 days. Stress testing was
      performed as often after as before coronary angiography. Importantly, stress
      testing was helpful in stratifying patients into low (equivocal or negative test)
      or high (positive test) risk groups (30 day death 3.1% vs. 5%). Stress testing
      was performed more often in non-US than US patients, and US patients were 3.5
      times more likely to undergo imaging as part of stress testing. However, the
      risks of 30-day death or MI; 6-month death, MI or revascularization; and 1-year
      death did not differ between US and non-US patients. CONCLUSION: Stress testing
      is commonly performed in low-risk NSTE ACS patients and provides modest
      additional prognostic information in this cohort. Significant geographical
      variation exists in the use of stress testing. Therefore, in the current practice
      environment where cardiac catheterization is often the first diagnostic modality
      used in patients with NSTE ACS, the role of non-invasive testing both before and
      after invasive procedure is in need of further study.

PMID- 18334474
TI  - Impact of collagen type I turnover on the long-term response to cardiac
      resynchronization therapy.
AB  - AIMS: We investigated whether collagen type I turnover influences the long-term
      response to cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Serum
      carboxy-terminal propeptide of procollagen type I or PICP (a marker of collagen
      type I synthesis) and carboxy-terminal telopeptide of collagen type I or CITP (a
      marker of collagen type I degradation) were measured in heart failure patients at
      baseline and after 1 year of CRT. Patients were categorized as responders or non
      responders if they increased the distance walked in 6 min by > or <10%,
      respectively. At baseline, the PICP:CITP ratio, an index of the degree of
      coupling between collagen type I synthesis and degradation was higher (P = 0.006)
      in responders than in non-responders. Whereas the PICP:CITP ratio decreased (P=
      0.000) after treatment in responders, it remained unchanged in non-responders.
      Thus, at 1-year, the PICP:CITP ratio was similar in the two groups of patients. A
      direct correlation (r = 0.289, P = 0.037) was found between the baseline
      PICP:CITP ratio and the change in the distance walked in 6 min in all patients.
      Receiver operating characteristics curves showed that a cut-off value of 14.4 for
      the PICP:CITP ratio provided 70% specificity and 63% sensitivity for the
      predicting response to CRT with a relative risk of 2.07 (95% confidence interval,
      0.98-4.39). CONCLUSION: Collagen type I turnover influences the long-term
      response to CRT. In addition, the ability of CRT to restore the balance between
      collagen type I synthesis and degradation is associated with a beneficial
      response.

PMID- 18334475
TI  - Risk factors for myocardial infarction in women and men: insights from the
      INTERHEART study.
AB  - AIMS: Coronary heart disease (CHD) is a leading cause of death among men and
      women globally. Women develop CHD about 10 years later than men, yet the reasons
      for this are unclear. The purpose of this report is to determine if differences
      in risk factor distributions exist between women and men across various age
      categories to help explain why women develop acute MI later than men. METHODS AND
      RESULTS: We used the INTERHEART global case-control study including 27 098
      participants from 52 countries, 6787 of whom were women. The median age of first
      acute MI was higher in women than men (65 vs. 56 years; P < 0.0001). Nine
      modifiable risk factors were associated with MI in women and men. Hypertension
      [2.95(2.66 -3.28) vs. 2.32(2.16-2.48)], diabetes [4.26(3.68-4.94) vs. 2.67(2.43
      2.94), physical activity [0.48(0.41-0.57) vs. 0.77(0.71-0.83)], and moderate
      alcohol use [0.41(0.34-0.50) vs. 0.88(0.82-0.94)] were more strongly associated
      with MI among women than men. The association of abnormal lipids, current
      smoking, abdominal obesity, high risk diet, and psychosocial stress factors with
      MI was similar in women and men. Risk factors associations were generally
      stronger among younger individuals compared to older women and men. The
      population attributable risk (PAR) of all nine risk factors exceeded 94%, and was
      similar among women and men (96 vs. 93%). Men were significantly more likely to
      suffer a MI prior to 60 years of age than were women, however, after adjusting
      for levels of risk factors, the sex difference in the probability of MI cases
      occurring before the age of 60 years was reduced by more than 80%. CONCLUSION:
      Women experience their first acute MI on average 9 years later than men. Nine
      modifiable risk factors are significantly associated with acute MI in both men
      and women and explain greater than 90% of the PAR. The difference in age of first
      MI is largely explained by the higher risk factor levels at younger ages in men
      compared to women.

PMID- 18334476
TI  - Should we abandon the common practice of withholding oral anticoagulation in
      paroxysmal atrial fibrillation?
AB  - AIMS: To assess the relation between the atrial fibrillation (AF) subtype and
      thrombo-embolic events. METHODS AND RESULTS: The observational Euro Heart Survey
      on AF (2003-04) enrolled 1509 paroxysmal, 1109 persistent, and 1515 permanent AF
      patients, according to the 2001 American College of Cardiology, American Heart
      Association, and the European Society of Cardiology guidelines definitions. A 1
      year follow-up was performed. Permanent AF patients had at baseline a worse
      stroke risk profile than paroxysmal and persistent AF patients. In paroxysmal AF,
      the risk for stroke, any thrombo-embolism, major bleeding and the combined
      endpoint of cardiovascular mortality, any thrombo-embolism, and major bleeding
      was comparable with persistent and permanent AF, in both univariable and
      multivariable analyses. Compared with AF patients without stroke, patients
      suffering from a stroke had a comparable frequency and duration of AF attacks,
      but tended to have a worse stroke risk profile at baseline. During 1 year
      following cardioversion, paroxysmal AF patients had a higher risk for stroke (P =
      0.029) and any thrombo-embolism (P = 0.001) than persistent AF patients.
      CONCLUSION: In the Euro Heart Survey, paroxysmal AF had a comparable risk for
      thrombo-embolic events as persistent and permanent AF. This observation
      strengthens the guideline recommendation not to consider the clinical AF subtype
      when deciding on anticoagulation.

PMID- 18334477
TI  - Atrial fibrillation subtypes, risk of stroke, and antithrombotic therapy.

PMID- 18334478
TI  - The structural basis for allosteric inhibition of a threonine-sensitive
      aspartokinase.
AB  - The commitment step to the aspartate pathway of amino acid biosynthesis is the
      phosphorylation of aspartic acid catalyzed by aspartokinase (AK). Most
      microorganisms and plants have multiple forms of this enzyme, and many of these
      isofunctional enzymes are subject to feedback regulation by the end products of
      the pathway. However, the archeal species Methanococcus jannaschii has only a
      single, monofunctional form of AK. The substrate l-aspartate binds to this
      recombinant enzyme in two different orientations, providing the first structural
      evidence supporting the relaxed regiospecificity previously observed with several
      alternative substrates of Escherichia coli AK ( Angeles, T. S., Hunsley, J. R.,
      and Viola, R. E. (1992) Biochemistry 31, 799-805 ). Binding of the nucleotide
      substrate triggers significant domain movements that result in a more compact
      quaternary structure. In contrast, the highly cooperative binding of the
      allosteric regulator l-threonine to multiple sites on this dimer of dimers leads
      to an open enzyme structure. A comparison of these structures supports a
      mechanism for allosteric regulation in which the domain movements induced by
      threonine binding causes displacement of the substrates from the enzyme,
      resulting in a relaxed, inactive conformation.

PMID- 18334479
TI  - Crystal structures of fission yeast histone chaperone Asf1 complexed with the
      Hip1 B-domain or the Cac2 C terminus.
AB  - The assembly of core histones onto eukaryotic DNA is modulated by several histone
      chaperone complexes, including Asf1, CAF-1, and HIRA. Asf1 is a unique histone
      chaperone that participates in both the replication-dependent and replication
      independent pathways. Here we report the crystal structures of the apo-form of
      fission yeast Asf1/Cia1 (SpAsf1N; residues 1-161) as well as its complexes with
      the B-domain of the fission yeast HIRA orthologue Hip1 (Hip1B) and the C-terminal
      region of the Cac2 subunit of CAF-1 (Cac2C). The mode of the fission yeast Asf1N
      Hip1B recognition is similar to that of the human Asf1-HIRA recognition,
      suggesting that Asf1N recognition of Hip1B/HIRA is conserved from yeast to
      mammals. Interestingly, Hip1B and Cac2C show remarkably similar interaction modes
      with Asf1. The binding between Asf1N and Hip1B was almost completely abolished by
      the D37A and L60A/V62A mutations in Asf1N, indicating the critical role of salt
      bridge and van der Waals contacts in the complex formation. Consistently, both of
      the aforementioned Asf1 mutations also drastically reduced the binding to Cac2C.
      These results provide a structural basis for a mutually exclusive Asf1-binding
      model of CAF-1 and HIRA/Hip1, in which Asf1 and CAF-1 assemble histones H3/H4
      (H3.1/H4 in vertebrates) in a replication-dependent pathway, whereas Asf1 and
      HIRA/Hip1 assemble histones H3/H4 (H3.3/H4 in vertebrates) in a replication
      independent pathway.

PMID- 18334480
TI  - ING2 as a novel mediator of transforming growth factor-beta-dependent responses
      in epithelial cells.
AB  - Members of the ING (inhibitor of growth) family of chromatin modifying proteins
      (ING1-ING5) have emerged as critical regulators of gene expression and cellular
      responses, suggesting that the ING proteins may impinge on specific signal
      transduction pathways and their mediated effects. Here, we demonstrate a role for
      the protein ING2 in mediating responses by the transforming growth factor (TGF)
      beta-Smad signaling pathway. We show that ING2 promotes TGF-beta-induced
      transcription. Both gain-of-function and RNA interference-mediated knockdown of
      endogenous ING2 reveal that ING2 couples TGF-beta signals to the induction of
      transcription and cell cycle arrest. We also find that the Smad-interacting
      transcriptional modulator SnoN interacts with ING2 and promotes the assembly of a
      protein complex containing SnoN, ING2, and Smad2. Knockdown of endogenous SnoN
      blocks the ability of ING2 to promote TGF-beta-dependent transcription, and
      conversely expression of SnoN augments ING2 enhancement of the TGF-beta response.
      Collectively, our data suggest that ING2 collaborates with SnoN to mediate TGF
      beta-induced Smad-dependent transcription and cellular responses.

PMID- 18334481
TI  - Isolated cytochrome c oxidase deficiency in G93A SOD1 mice overexpressing CCS
      protein.
AB  - G93A SOD1 transgenic mice overexpressing CCS protein develop an accelerated
      disease course that is associated with enhanced mitochondrial pathology and
      increased mitochondrial localization of mutant SOD1. Because these results
      suggest an effect of mutant SOD1 on mitochondrial function, we assessed the
      enzymatic activities of mitochondrial respiratory chain complexes in the spinal
      cords of CCS/G93A SOD1 and control mice. CCS/G93A SOD1 mouse spinal cord
      demonstrates a 55% loss of complex IV (cytochrome c oxidase) activity compared
      with spinal cord from age-matched non-transgenic or G93A SOD1 mice. In contrast,
      CCS/G93A SOD1 spinal cord shows no reduction in the activities of complex I, II,
      or III. Blue native gel analysis further demonstrates a marked reduction in the
      levels of complex IV but not of complex I, II, III, or V in spinal cords of
      CCS/G93A SOD1 mice compared with non-transgenic, G93A SOD1, or CCS/WT SOD1
      controls. With SDS-PAGE analysis, spinal cords from CCS/G93A SOD1 mice showed
      significant decreases in the levels of two structural subunits of cytochrome c
      oxidase, COX1 and COX5b, relative to controls. In contrast, CCS/G93A SOD1 mouse
      spinal cord showed no reduction in levels of selected subunits from complexes I,
      II, III, or V. Heme A analyses of spinal cord further support the existence of
      cytochrome c oxidase deficiency in CCS/G93A SOD1 mice. Collectively, these
      results establish that CCS/G93A SOD1 mice manifest an isolated complex IV
      deficiency which may underlie a substantial part of mutant SOD1-induced
      mitochondrial cytopathy.

PMID- 18334482
TI  - Redefining the role of metallothionein within the injured brain: extracellular
      metallothioneins play an important role in the astrocyte-neuron response to
      injury.
AB  - A number of intracellular proteins that are protective after brain injury are
      classically thought to exert their effect within the expressing cell. The
      astrocytic metallothioneins (MT) are one example and are thought to act via
      intracellular free radical scavenging and heavy metal regulation, and in
      particular zinc. Indeed, we have previously established that astrocytic MTs are
      required for successful brain healing. Here we provide evidence for a
      fundamentally different mode of action relying upon intercellular transfer from
      astrocytes to neurons, which in turn leads to uptake-dependent axonal
      regeneration. First, we show that MT can be detected within the extracellular
      fluid of the injured brain, and that cultured astrocytes are capable of actively
      secreting MT in a regulatable manner. Second, we identify a receptor, megalin,
      that mediates MT transport into neurons. Third, we directly demonstrate for the
      first time the transfer of MT from astrocytes to neurons over a specific time
      course in vitro. Finally, we show that MT is rapidly internalized via the cell
      bodies of retinal ganglion cells in vivo and is a powerful promoter of axonal
      regeneration through the inhibitory environment of the completely severed mature
      optic nerve. Our work suggests that the protective functions of MT in the central
      nervous system should be widened from a purely astrocytic focus to include
      extracellular and intra-neuronal roles. This unsuspected action of MT represents
      a novel paradigm of astrocyte-neuronal interaction after injury and may have
      implications for the development of MT-based therapeutic agents.

PMID- 18334483
TI  - The CB(2) cannabinoid receptor controls myeloid progenitor trafficking:
      involvement in the pathogenesis of an animal model of multiple sclerosis.
AB  - Cannabinoids are potential agents for the development of therapeutic strategies
      against multiple sclerosis. Here we analyzed the role of the peripheral CB(2)
      cannabinoid receptor in the control of myeloid progenitor cell trafficking toward
      the inflamed spinal cord and their contribution to microglial activation in an
      animal model of multiple sclerosis (experimental autoimmune encephalomyelitis,
      EAE). CB(2) receptor knock-out mice showed an exacerbated clinical score of the
      disease when compared with their wild-type littermates, and this occurred in
      concert with extended axonal loss, T-lymphocyte (CD4(+)) infiltration, and
      microglial (CD11b(+)) activation. Immature bone marrow-derived CD34(+) myeloid
      progenitor cells, which play a role in neuroinflammatory pathologies, were shown
      to express CB(2) receptors and to be abundantly recruited toward the spinal cords
      of CB(2) knock-out EAE mice. Bone marrow-derived cell transfer experiments
      further evidenced the increased contribution of these cells to microglial
      replenishment in the spinal cords of CB(2)-deficient animals. In line with these
      observations, selective pharmacological CB(2) activation markedly reduced EAE
      symptoms, axonal loss, and microglial activation. CB(2) receptor manipulation
      altered the expression pattern of different chemokines (CCL2, CCL3, CCL5) and
      their receptors (CCR1, CCR2), thus providing a mechanistic explanation for its
      role in myeloid progenitor recruitment during neuroinflammation. These findings
      demonstrate the protective role of CB(2) receptors in EAE pathology; provide
      evidence for a new site of CB(2) receptor action, namely the targeting of myeloid
      progenitor trafficking and its contribution to microglial activation; and support
      the potential use of non-psychoactive CB(2) agonists in therapeutic strategies
      for multiple sclerosis and other neuroinflammatory disorders.

PMID- 18334484
TI  - The mechanism of autocatalytic activation of plant-type L-asparaginases.
AB  - Plant l-asparaginases and their bacterial homologs, such as EcAIII found in
      Escherichia coli, form a subgroup of the N-terminal nucleophile (Ntn)-hydrolase
      family. In common with all Ntn-hydrolases, they are expressed as inactive
      precursors that undergo activation in an autocatalytic manner. The maturation
      process involves intramolecular hydrolysis of a single peptide bond, leading to
      the formation of two subunits (alpha and beta) folded as one structural domain,
      with the nucleophilic Thr residue located at the freed N terminus of subunit
      beta. The mechanism of the autocleavage reaction remains obscure. We have
      determined the crystal structure of an active site mutant of EcAIII, with the
      catalytic Thr residue substituted by Ala (T179A). The modification has led to a
      correctly folded but unprocessed molecule, revealing the geometry and molecular
      environment of the scissile peptide bond. The autocatalytic reaction is analyzed
      from the point of view of the Thr(179) side chain rotation, identification of a
      potential general base residue, and the architecture of the oxyanion hole.

PMID- 18334485
TI  - Culturing of human mesenchymal stem cells as three-dimensional aggregates induces
      functional expression of CXCR4 that regulates adhesion to endothelial cells.
AB  - Culture-expanded human mesenchymal stem cells (hMSCs) are increasingly used in a
      variety of preclinical and clinical studies. However, these cells have a low rate
      of engraftment to bone marrow or damaged tissues. Several laboratories have shown
      that during isolation and subculturing mesenchymal stem cells quickly lose the
      expression of CXCR4, the key receptor responsible for lymphocytes and
      hematopoietic stem cell homing. Here we show that culturing of hMSCs as three
      dimensional aggregates (hMSC spheroids) restores CXCR4 functional expression.
      Expression of CXCR4 inversely correlates with the secretion of SDF-1 by hMSCs.
      Cells from hMSC spheroids up-regulate expression of CD49b, the alpha2 integrin
      subunit, and suppress the expression of CD49d, the alpha4 integrin subunit.
      Transfer of cells from the spheroids back to a monolayer suppresses the
      expression of CXCR4 and CD49b and restores the expression of CD49d. Treatment of
      cells from the spheroids with SDF-1 leads to CXCR4 internalization and activation
      of ERK-1,2. Adhesion of hMSCs to human umbilical vein endothelial cells (HUVECs)
      was investigated. SDF-1, AMD-3100, or exposure of HUVECs to hypoxia did not
      affect adhesion of hMSCs from a monolayer to HUVECs. Adhesion of cells from hMSC
      spheroids to HUVECs was stimulated by SDF-1, AMD-3100, or by exposure of HUVECs
      to hypoxia. Stimulatory effects of hypoxia and addition of SDF-1 or AMD-3100 were
      not additive. Overall, our data indicate that the expression of CXCR4 by hMSCs
      regulates hMSC adhesion to endothelial cells.

PMID- 18334486
TI  - Tousled-mediated activation of Aurora B kinase does not require Tousled kinase
      activity in vivo.
AB  - The Aurora kinases comprise an evolutionarily conserved protein family that is
      required for a variety of cell division events, including spindle assembly,
      chromosome segregation, and cytokinesis. Emerging evidence suggests that once
      phosphorylated, a subset of Aurora substrates can enhance Aurora kinase activity.
      Our previous work revealed that the Caenorhabditis elegans Tousled-like kinase
      TLK-1 is a substrate and activator of the AIR-2 Aurora B kinase in vitro and that
      partial loss of TLK-1 enhances the mitotic defects of an air-2 mutant. However,
      given that these experiments were performed in vitro and with partial loss of
      function alleles in vivo, a necessary step forward in our understanding of the
      relationship between the Aurora B and Tousled kinases is to prove that TLK-1
      expression is sufficient for Aurora B activation in vivo. Here, we report that
      heterologous expression of wild-type and kinase-inactive forms of TLK-1
      suppresses the lethality of temperature-sensitive mutants of the yeast Aurora B
      kinase Ipl1. Moreover, kinase-dead TLK-1 associates with and augments the
      activity of Ipl1 in vivo. Together, these results provide critical and compelling
      evidence that Tousled has a bona fide kinase-independent role in the activation
      of Aurora B kinases in vivo.

PMID- 18334487
TI  - Protein phosphatase 2A negatively regulates integrin alpha(IIb)beta(3) signaling.
AB  - Integrin alpha(IIb)beta(3) activation is critical for platelet physiology and is
      controlled by signal transduction through kinases and phosphatases. Compared with
      kinases, a role for phosphatases in platelet integrin alpha(IIb)beta(3) signaling
      is less understood. We report that the catalytic subunit of protein phosphatase
      2A (PP2Ac) associates constitutively with the integrin alpha(IIb)beta(3) in
      resting platelets and in human embryonal kidney 293 cells expressing
      alpha(IIb)beta(3). The membrane proximal KVGFFKR sequence within the cytoplasmic
      domain of integrin alpha(IIb) is sufficient to support a direct interaction with
      PP2Ac. Fibrinogen binding to alpha(IIb)beta(3) during platelet adhesion decreased
      integrin-associated PP2A activity and increased the phosphorylation of a PP2A
      substrate, vasodilator associated phosphoprotein. Overexpression of PP2Ac(alpha)
      in 293 cells decreased alpha(IIb)beta(3)-mediated adhesion to immobilized
      fibrinogen. Conversely, small interference RNA mediated knockdown of endogenous
      PP2Ac(alpha) expression in 293 cells, enhanced extracellular signal-regulated
      kinase (ERK1/2) and p38 activation, and accelerated alpha(IIb)beta(3) adhesion to
      fibrinogen and von Willebrand factor. Inhibition of ERK1/2, but not p38
      activation, abolished the increased adhesiveness of PP2Ac (alpha)-depleted 293
      cells to fibrinogen. Furthermore, knockdown of PP2A(calpha) expression in bone
      marrow-derived murine megakaryocytes increased soluble fibrinogen binding induced
      by protease-activated receptor 4-activating peptide. These studies demonstrate
      that PP2Ac (alpha) can negatively regulate integrin alpha(IIb)beta(3) signaling
      by suppressing the ERK1/2 signaling pathway.

PMID- 18334488
TI  - Fat-specific protein 27 regulates storage of triacylglycerol.
AB  - FSP27 (fat-specific protein 27) is a member of the cell death-inducing DNA
      fragmentation factor-alpha-like effector (CIDE) family. Although Cidea and Cideb
      were initially characterized as activators of apoptosis, recent studies have
      demonstrated important metabolic roles for these proteins. In this study, we
      investigated the function of another member of this family, FSP27 (Cidec), in
      apoptosis and adipocyte metabolism. Although overexpression of FSP27 is
      sufficient to increase apoptosis of 293T and 3T3-L1 cells, more physiological
      levels of expression stimulate spontaneous lipid accumulation in several cell
      types without induction of adipocyte genes. Increased triacylglycerol is likely
      due to decreased beta-oxidation of nonesterified fatty acids. Altered flux of
      fatty acids into triacylglycerol may be a direct effect of FSP27 function, which
      is localized to lipid droplets in 293T cells and 3T3-L1 adipocytes. Stable
      knockdown of FSP27 during adipogenesis of 3T3-L1 cells substantially decreases
      lipid droplet size, increases mitochondrial and lipid droplet number, and
      modestly increases glucose uptake and lipolysis. Expression of FSP27 in
      subcutaneous adipose tissue of a human diabetes cohort decreases with total fat
      mass but is not associated with measures of insulin resistance (e.g. homeostasis
      model assessment). Together, these data indicate that FSP27 binds to lipid
      droplets and regulates their enlargement.

PMID- 18334489
TI  - Proteogenomics: needs and roles to be filled by proteomics in genome annotation.
AB  - While genome sequencing efforts reveal the basic building blocks of life, a
      genome sequence alone is insufficient for elucidating biological function. Genome
      annotation--the process of identifying genes and assigning function to each gene
      in a genome sequence--provides the means to elucidate biological function from
      sequence. Current state-of-the-art high-throughput genome annotation uses a
      combination of comparative (sequence similarity data) and non-comparative (ab
      initio gene prediction algorithms) methods to identify protein-coding genes in
      genome sequences. Because approaches used to validate the presence of predicted
      protein-coding genes are typically based on expressed RNA sequences, they cannot
      independently and unequivocally determine whether a predicted protein-coding gene
      is translated into a protein. With the ability to directly measure peptides
      arising from expressed proteins, high-throughput liquid chromatography-tandem
      mass spectrometry-based proteomics approaches can be used to verify coding
      regions of a genomic sequence. Here, we highlight several ways in which high
      throughput tandem mass spectrometry-based proteomics can improve the quality of
      genome annotations and suggest that it could be efficiently applied during the
      gene calling process so that the improvements are propagated through the
      subsequent functional annotation process.

PMID- 18334490
TI  - The CTX-M-15-producing Escherichia coli diffusing clone belongs to a highly
      virulent B2 phylogenetic subgroup.
AB  - OBJECTIVES: A clone of CTX-M-15-producing Escherichia coli has recently been
      reported to be spreading through Europe and Africa. The aim of this work was to
      thoroughly characterize this clone. MATERIALS AND METHODS: Representative
      isolates of this clone were subjected to multilocus sequence typing, O typing,
      virulence gene detection, adhesion assay on human cells, biofilm production assay
      and mouse lethality assay. RESULTS: The clone: (i) belongs to a unique B2
      phylogenetic subgroup encompassing the pyelonephritogenic diffusely adhering
      EC7372 strain; (ii) exhibits a specific O25b molecular subtype; (iii) is
      identical to the E. coli clone O25:H4-ST131 producing CTX-M-15; (iv) produces
      biofilm; and (v) is highly virulent in mice despite lacking classical
      extraintestinal pathogenicity islands (except for high pathogenicity island) and
      the afa/dra gene. CONCLUSIONS: The CTX-M-15-producing E. coli diffusing clone is
      associated with a high level of antibiotic resistance and with high virulence,
      showing that, under certain selective pressures, the previously observed trade
      off between resistance and virulence may not apply.

PMID- 18334491
TI  - Heterogeneity of susceptibility to fluoroquinolones in Bartonella isolates from
      Australia reveals a natural mutation in gyrA.
AB  - OBJECTIVES: Bartonella sp. are intracellular bacteria associated with an
      increasing number of clinical manifestations but with few published data on in
      vitro susceptibility testing of antibiotics. Our objective was to evaluate in
      vitro antibiotic susceptibilities of 20 new Bartonella isolates from animals in
      Australia. METHODS: MICs were determined using Etest assay on Columbia agar
      supplemented with 5% horse blood. The presence of mutations in the quinolone
      resistance-determining region (QRDR) of gyrA was searched for after PCR
      amplification and DNA sequencing using specific oligonucleotide primers. RESULTS:
      Bartonella isolates from Australia were susceptible to rifampicin, tetracyclines,
      beta-lactam and macrolide compounds but were resistant to vancomycin. We found
      heterogeneity of susceptibility for fluoroquinolones with ciprofloxacin being
      more effective (MICs from 0.06 to 0.5 mg/L) than ofloxacin (MICs from 0.5 to 4
      mg/L). This heterogeneity was linked to a natural mutation Ser-83-->Ala
      (Escherichia coli numbering) in the QRDR. Surprisingly, this mutation was also
      present in the QRDR of Bartonella henselae, Bartonella quintana and Bartonella
      bacilliformis. CONCLUSIONS: Etest is a sensitive and reliable assay for
      evaluation of antibiotic susceptibility in the genus Bartonella. The higher
      sensitivity of this method allowed us to detect heterogeneity of susceptibility
      among fluoroquinolones that was associated with natural mutation in the QRDR of
      the DNA gyrase. Because a high level of resistance to fluoroquinolones due to a
      second mutation may be obtained easily in vitro, we believe that fluoroquinolone
      compounds should be avoided for the treatment of any Bartonella-related diseases.

PMID- 18334492
TI  - Multidrug-resistant Providencia stuartii expressing extended-spectrum beta
      lactamase PER-1, originating in Kosovo.

PMID- 18334493
TI  - Novel structural analogues of piperine as inhibitors of the NorA efflux pump of
      Staphylococcus aureus.
AB  - OBJECTIVES: Evaluation of novel synthetic analogues of piperine as inhibitors of
      multidrug efflux pump NorA of Staphylococcus aureus. METHODS: A library of
      piperine-derived compounds was evaluated for their potential to inhibit ethidium
      bromide efflux in NorA-overexpressing S. aureus SA 1199B. The active compounds
      were then individually combined with ciprofloxacin to study the potentiation of
      ciprofloxacin's activity. RESULTS: Based on the efflux inhibition assay, a
      library of 200 compounds was screened. Three piperine analogues, namely SK-20, SK
      56 and SK-29, were found to be the most potent inhibitors of the NorA efflux
      pump. These inhibitors acted in a synergistic manner with ciprofloxacin, by
      substantially increasing its activity against both NorA-overexpressing and wild
      type S. aureus isolates. These analogues were 2- to 4-fold more potent than
      piperine at a significantly lower minimal effective concentration. Furthermore,
      these inhibitors also significantly suppressed the in vitro emergence of
      ciprofloxacin-resistant S. aureus. CONCLUSIONS: A newly identified class of
      compounds derived from a natural amide, piperine, is more potent than the parent
      molecule in potentiating the activity of ciprofloxacin through the inhibition of
      the NorA efflux pump. These molecules may prove useful in augmenting the
      antibacterial activities of fluoroquinolones in a clinical setting.

PMID- 18334494
TI  - Risk factors for nephrotoxicity associated with continuous vancomycin infusion in
      outpatient parenteral antibiotic therapy.
AB  - OBJECTIVES: Continuous vancomycin infusion is increasingly used for outpatient
      management of infections, but the relationship between vancomycin and
      nephrotoxicity is controversial. We investigated the risk factors associated with
      nephrotoxicity in this setting. METHODS: A retrospective cohort study of patients
      receiving continuous vancomycin infusion as outpatient parenteral antibiotic
      therapy (OPAT) was performed. The likelihood of developing nephrotoxicity (> or
      =50% increase in serum creatinine from baseline) was evaluated in relation to
      demographic variables, underlying co-morbidities, infectious disease diagnoses,
      concomitant drug exposures and vancomycin concentration. Logistic regression was
      used to determine the association of various variables. Classification and
      regression tree analysis was used to determine the most significant breakpoint
      for continuous variables. RESULTS: We examined 102 adult patients between January
      2004 and June 2007. The mean +/- SD age, baseline serum creatinine and steady
      state vancomycin concentration were 48.2 +/- 17.6 years, 78.0 +/- 32.5 micromol/L
      and 15.5 +/- 10.8 mg/L, respectively. The majority of the patients (66.7%) were
      treated for bone and joint infection. The cumulative incidence of nephrotoxicity
      was 15.7%. Nephrotoxicity was found to be associated with hypertension [odds
      ratio (OR) 5.302 (95% confidence interval (CI) 1.159-24.246), P = 0.031],
      exposure to aminoglycosides [OR 6.594 (95% CI 1.026-42.385), P = 0.047], loop
      diuretics [OR 8.123 (95% CI 1.449-45.528), P = 0.017], and steady-state
      vancomycin concentration > or =28 mg/L [OR 21.236 (95% CI 2.687-167.857), P =
      0.004]. CONCLUSIONS: We have identified independent risk factors for
      nephrotoxicity in patients receiving continuous infusion vancomycin in OPAT. A
      serum steady-state vancomycin concentration > or =28 mg/L markedly increases the
      risk.

PMID- 18334495
TI  - Supervising children during parental distractions.
AB  - OBJECTIVE: To examine the effects of parenting distractions on supervising
      behaviors in relation to child risky behaviors. METHODS: Forty preschool-aged
      children and their parents were randomly assigned to occupy a simulated home
      living room for 45 min with the parent involved in either (a) no planned
      distraction, (b) a telephone call distraction, (c) a TV show distraction, or (d)
      a computer assignment distraction. Parent and child behaviors were recorded and
      coded. RESULTS: Parent supervising behaviors were significantly intercorrelated
      but revealed no relation to risky child behavior. Children showed higher risky
      behavior during parental distractions and steadily over time when parent
      distractions occurred. Additionally, younger children were more likely to engage
      in risky behavior when compared to older children. CONCLUSIONS: Parents showed
      significant reductions in their ability to supervise children during
      distractions, limiting the ability to provide education or to take immediate
      action necessary to prevent or minimize possible injuries.

PMID- 18334496
TI  - Serum urea concentration and the risk of hepatotoxicity after paracetamol
      overdose.
AB  - BACKGROUND: Glutathione depletion increases the incidence of toxicity after
      paracetamol overdose. Risk factors for toxicity, including chronic ethanol excess
      and malnutrition, are associated with low serum urea concentrations. Therefore,
      we hypothesized that low serum urea concentration might itself be predictive of
      hepatotoxicity in patients that present to hospital after paracetamol overdose.
      METHODS: The present study prospectively collected data from 1085 patients
      attending the Emergency Department after paracetamol overdose. Hepatotoxicity was
      predefined by prothrombin time ratio >1.3 or alanine transaminase > or = 1000
      U/l. Serum urea concentrations were considered in a stepwise multiple regression
      analysis that included paracetamol dose, co-ingestion of ethanol and other drugs,
      serum concentration, N-acetylcysteine, interval to treatment, vomiting and serum
      creatinine. RESULTS: Median (IQR) serum urea concentrations were 3.3 mmol/l (2.7
      4.2 mmol/l) in those without risk factors, compared with 3.0 mmol/l (2.4-3.9
      mmol/l) in those with chronic excess ethanol intake (P < 0.001 by Mann Whitney
      test) and 2.5 mmol/l (1.9-2.8 mmol/l) in patients with other risk factors (P <
      0.001). Multivariate analysis found that serum urea concentrations were not
      independently associated with hepatotoxicity. CONCLUSION: Low serum urea
      concentration is not an independent risk factor for hepatotoxicity after
      paracetamol overdose.

PMID- 18334497
TI  - DXA scanning in clinical practice.
AB  - Dual-energy X-ray absorptiometry (DXA) is recognized as the reference method to
      measure bone mineral density (BMD) with acceptable accuracy errors and good
      precision and reproducibility. The World Health Organization (WHO) has
      established DXA as the best densitometric technique for assessing BMD in
      postmenopausal women and based the definitions of osteopenia and osteoporosis on
      its results. DXA allows accurate diagnosis of osteoporosis, estimation of
      fracture risk and monitoring of patients undergoing treatment. However, when DXA
      studies are performed incorrectly, it can lead to major mistakes in diagnosis and
      therapy. This article reviews the fundamentals of positioning, scan analysis and
      interpretation of DXA in clinical practice.

PMID- 18334498
TI  - Pulmonary actinomycosis in a patient with diffuse systemic sclerosis treated with
      infliximab.

PMID- 18334499
TI  - Incidence and clinical significance of left ventricular thrombus in tako-tsubo
      cardiomyopathy assessed with echocardiography.
AB  - BACKGROUND: Left ventricular (LV) thrombus is a known complication of tako-tsubo
      cardiomyopathy (TC). However, current literature almost exclusively consists of
      isolated case reports. The aim of this study was to determine the incidence and
      clinical significance of LV thrombus formation in TC. METHODS AND RESULTS: Over a
      33-month period 52 patients with TC were assembled into a database at our
      institution. A retrospective database search was performed to identify patients
      with LV thrombus among these patients. LV thrombus, by echocardiography, was
      discovered in four patients[(8%); 95% confidence interval 3-19%]. Thrombus was
      present at the time of diagnosis in three patients. In one patient thrombus was
      absent initially and developed later. The LV apex was the site of thrombus
      formation in two patients, but the true apex was spared in the other two. All
      four patients had elevated serum levels of C-reactive protein (CRP). Two patients
      also had thrombocytosis. Treatment with low molecular weight heparin (LMWH) led
      to resolution of thrombus in all cases. CONCLUSION: Our findings suggest that LV
      thrombus is a noteworthy complication in TC. It can occur both at initial
      presentation or at anytime later during the disease course. Elevated CRP levels
      and thrombocytosis may indicate a higher risk of thrombus formation.

PMID- 18334500
TI  - Evidence from nonrandomized studies: a case study on the estimation of causal
      effects.
AB  - Although randomized controlled trials are regarded as the gold standard for
      comparison of treatments, evidence from observational studies is still relevant.
      To cope with the problem of possible confounding in these studies, investigators
      need methods for analyzing their results which adjust for confounders and lead to
      unbiased estimation of the treatment effect. In this paper, the authors describe
      the main principles of three statistical methods for doing this. The first method
      is the classical approach of a multiple regression model including the effects of
      treatment and covariates. This considers the relation between prognostic factors
      and the outcome variable as a relevant criterion for adjustment. The second
      method is based on the propensity score, focusing on the relation between
      prognostic factors and treatment assignment. The third method is an ecologic
      approach using a grouped treatment variable, which may aid in avoiding
      confounding by indication. These approaches are applied to a partially randomized
      trial conducted in 720 German breast cancer patients between 1984 and 1997. The
      study had a comprehensive cohort study design that included recruitment of
      patients who had consented to participation but not to randomization because of a
      preference for one of the treatments. This design offers a unique opportunity to
      contrast results from the nonrandomized portion of a study with those for a
      randomized subcohort as a reference.

PMID- 18334501
TI  - The association between obesity and the prevalence of low back pain in young
      adults: the Cardiovascular Risk in Young Finns Study.
AB  - Both low back pain (LBP) and obesity are common public health problems, yet their
      relation remains controversial. The aim of this study was to investigate the
      associations between weight-related factors and the prevalence of LBP in young
      adults in Finland. Participants in the ongoing Cardiovascular Risk in Young Finns
      Study aged 24-39 years were included (N = 2,575). In 2001, 31.2% of men and 39.5%
      of women reported LBP with recovery within a month or recurrent or continuous
      pain during the preceding 12 months. For women only, those with higher body mass
      index, waist circumference, hip circumference, waist-to-hip ratio, serum leptin
      level, and C-reactive protein level showed an increased prevalence of LBP. With
      all weight-related factors in the model, only waist circumference was related to
      LBP in women. For women, the odds ratios of LBP were 1.2 (95% confidence
      interval: 0.8, 1.8) for a waist circumference of 80-87.9 cm and 1.8 (95%
      confidence interval: 1.0, 3.2) for a waist circumference of > or =88 cm compared
      with a waist circumference of <80 cm. This association was independent of C
      reactive protein, leptin, and adiponectin levels. The authors' findings in a
      relatively young population suggest that abdominal obesity may increase the risk
      of LBP in women.

PMID- 18334502
TI  - Mechanisms of organogenesis of primary lymphoid follicles.
AB  - Primary lymphoid follicles (PLFs) in secondary lymphoid tissue (SLT) of mammals
      are the backbone for the formation of follicular dendritic cell (FDC) networks.
      These are important for germinal center reactions during which affinity
      maturation creates optimized antibodies in adaptive immune responses. In the
      context of organogenesis, molecular requirements for the formation of follicles
      have been identified. The present study complements these findings with a
      simulation of the dynamics of the PLF formation, and a critical analysis of the
      relevant molecular interactions. In contrast to other problems of pattern
      formation, the homeostasis of cell populations in SLTs is not governed by a
      growth-death balance but by a flow equilibrium of migrating cells. The influx of
      cells into these tissues has been extensively studied. However, less information
      is available about the efflux of lymphocytes from SLTs. This study formulates the
      minimal requirements for cell efflux that guarantee a flow equilibrium and, thus,
      a stable PLF. The model predicts that in addition to already identified
      regulatory mechanisms, a negative regulation of the generation of FDCs is
      required. Furthermore, a comparison with data concerning the microanatomy of SLTs
      yields the conclusion that dynamical changes of the lymphatic endothelium during
      the formation of FDC networks are necessary to understand the genesis and
      maintenance of follicles.

PMID- 18334503
TI  - NK cells and NKT cells collaborate in host protection from methylcholanthrene
      induced fibrosarcoma.

PMID- 18334504
TI  - Implementing a service users' framework for cancer care in primary care: an
      action research study.
AB  - BACKGROUND: We previously facilitated the development of a service-user designed
      framework for providing proactive care for people with cancer in the community.
      OBJECTIVE: To validate this framework in clinical practice. METHODS: We used an
      action research approach, helping five diverse general practices in the South of
      Scotland to implement the care framework. The process and outcomes were evaluated
      using in-depth interviews (18 patients and their family carers and 49 health
      professionals), participant observation and an ongoing dialogue between the
      practices, the research team and the original user groups. RESULTS: Practices
      implemented the framework in a variety of ways. In general, they used their own
      customized cancer register to improve communication within the practice and began
      to offer proactive care from a diagnosis of cancer, not just when the disease
      became advanced. Local innovations included an intranet-based register,
      information sheets and regular multidisciplinary meetings. Patients, family
      carers and professionals suggested that the framework had helped achieve
      continuity of care, teamwork, proactive care and improved support and information
      for patients and carers. CONCLUSIONS: Proactive personalized care can be improved
      in primary care for patients with cancer and their family carers through flexible
      adoption of a framework to embrace key characteristics of good care, as perceived
      by patients and carers, throughout the illness. Practices can achieve this by
      choosing approaches suited to their setting, experiences, structure and
      resources.

PMID- 18334505
TI  - An induced mass spawn of the hermaphroditic lion-paw scallop, Nodipecten
      subnodosus: genetic assignment of maternal and paternal parentage.
AB  - The Pacific lion-paw scallop is commonly propagated for aquaculture by induced
      mass spawns of few individuals. Parentage of a mass spawn of this species has not
      been evaluated nor has the maternal and paternal contribution of each of these
      functional hermaphrodites to the progeny. Genotypes of 6 spawners and 374
      resulting progeny at 6 microsatellite loci were coupled with mitochondrial DNA
      sequencing to assign maternal and paternal parentage. After the identification of
      a high proportion of null alleles (9.7%), microsatellite data revealed that 51.7%
      of the progenies were full siblings, with a significant, unequal contribution of
      the 6 spawners to the progeny. Three progenies were the result of self
      fertilization. All spawners contributed paternally (though unequally); however, 2
      spawners were the maternal parents of all but 7 progenies resulting in a variance
      effective population size of 3.52. DNA sequencing confirmed 4 microsatellite
      mutations within 4476 alleles scored, all in the paternal germ line. With minor
      exception, the loci conformed to Mendelian rules of segregation when null alleles
      were accounted for, and 2 loci were found to be linked. These results lend
      insight to the genetic composition of induced mass spawns and provide a basis for
      the development of more effective spawning techniques.

PMID- 18334507
TI  - Mitochondrial DNA sequence phylogeny of 4 populations of the widely distributed
      cynomolgus macaque (Macaca fascicularis fascicularis).
AB  - We studied the mitochondrial DNA (mtDNA) polymorphism of 304 Macaca fascicularis
      fascicularis (M. f. fascicularis) individuals, representative of 4 cynomolgus
      macaque populations (Indochina, Indonesia, Philippines, and Mauritius). By
      sequencing a 590-bp fragment in the hypervariable II region of the D-loop region,
      we defined 70 haplotypes. The homologous region was also characterized in 22
      Chinese Macaca mulatta and 2 Macaca sylvanus. The phylogenetic analysis confirms
      the monophyly of M. f. fascicularis and defines 2 haplotype groups inside the M.
      f. fascicularis clade: one "insular," encompassing 6 Philippines, 2 Mauritius,
      and 31 Indonesian haplotypes, the other "continental" that contains all
      Indochinese and 6 Indonesian haplotypes. Continental and insular group divergence
      time was estimated to be approximately 10(6) years before present (BP). Among
      Indonesian haplotypes, some have a continental origin. This suggests either
      direct migration from mainland to Indonesia or that remnant lineages from an
      ancient population genetically close to the mainland (i.e., in the Sunda Shelf,
      <550 000 years BP) were subsequently brought southward to Indonesia. The low
      nucleotide diversity in the Philippines population suggests a bottleneck
      following colonization by Indonesian individuals, around 110 000 years BP. mtDNA
      and further observations of nuclear genetic data corroborate the mixed origin
      (Indonesian/continental) hypothesis of Mauritius individuals and a population
      bottleneck.

PMID- 18334506
TI  - Fitness of transgenic Anopheles stephensi mosquitoes expressing the SM1 peptide
      under the control of a vitellogenin promoter.
AB  - Three transgenic Anopheles stephensi lines were established that strongly inhibit
      transmission of the mouse malaria parasite Plasmodium berghei. Fitness of the
      transgenic mosquitoes was assessed based on life table analysis and competition
      experiments between transgenic and wild-type mosquitoes. Life table analysis
      indicated low fitness load for the 2 single-insertion transgenic mosquito lines
      VD35 and VD26 and no load for the double-insertion transgenic mosquito line VD9.
      However, in cage experiments, where each of the 3 homozygous transgenic
      mosquitoes was mixed with nontransgenic mosquitoes, transgene frequency of all 3
      lines decreased with time. Further experiments suggested that reduction of
      transgene frequency is a consequence of reduced mating success, reduced
      reproductive capacity, and/or insertional mutagenesis, rather than expression of
      the transgene itself. Thus, for transgenic mosquitoes released in the field to be
      effective in reducing malaria transmission, a driving mechanism will be required.

PMID- 18334508
TI  - Has research informed us on the practical drug treatment of schizophrenia?

PMID- 18334509
TI  - Gene expression in the etiology of schizophrenia.
AB  - Gene expression represents a fundamental interface between genes and environment
      in the development and ongoing plasticity of the human brain. Individual
      differences in gene expression are likely to underpin much of human diversity,
      including psychiatric illness. In the past decade, the development of microarray
      and proteomic technology has enabled global description of gene expression in
      schizophrenia. However, it is difficult on the basis of gene expression assays
      alone to distinguish between those changes that constitute primary etiology and
      those that reflect secondary pathology, compensatory mechanisms, or confounding
      influences. In this respect, tests of genetic association with schizophrenia will
      be instructive because changes in gene expression that result from gene variants
      that are associated with the disorder are likely to be of primary etiological
      significance. However, regulatory polymorphism is extremely difficult to
      recognize on the basis of sequence interrogation alone. Functional assays at the
      messenger RNA and/or protein level will be essential in elucidating the molecular
      mechanisms underlying genetic association with schizophrenia and are likely to
      become increasingly important in the identification of regulatory variants with
      which to test for association with the disorder and related traits. Once
      established, etiologically relevant changes in gene expression can be
      recapitulated in model systems in order to elucidate the molecular and
      physiological pathways that may ultimately give rise to the condition.

PMID- 18334510
TI  - Chronic autoimmune thyroiditis (Hashimoto's thyroiditis) in patients with MALT
      lymphoma.
AB  - BACKGROUND: Autoimmune diseases have been implicated in the genesis of MALT
      lymphoma of various localizations. The development of thyroidal MALT lymphoma has
      been described as an adverse event in patients suffering from long-standing
      chronic autoimmune thyroiditis (CAT, Hashimoto's thyroiditis). The percentage and
      possible association between CAT and extrathyroidal MALT lymphoma, however, have
      not been assessed so far. PATIENTS AND METHODS: A retrospective analysis of 80
      patients with MALT lymphoma diagnosed and treated at our institution identified a
      total of 13 patients (16%) with MALT lymphoma suffering from an underlying CAT.
      Patient characteristics including site of disease, stage, genetic changes and
      clinical course were assessed and evaluated. RESULTS: In total, 10 patients were
      female and 3 male, with the median age being 57 years (range: 31-80). Four
      patients suffered from thyroidal lymphoma and nine patients had extrathyroidal
      lymphoma (four gastric, two orbital, one small intestinal and two salivary gland
      lymphomas). Three patients had a long-standing history of CAT at diagnosis of
      MALT lymphoma, while CAT was discovered during staging and clinical work-up of
      MALT lymphoma in the remaining 10 patients. All 13 patients had localized
      disease, i.e. stage I or II. Only one of the four patients with gastric MALT
      lymphoma responded to antibiotic treatment against Helicobacter pylori infection.
      Genetic aberrations were detected in four patients, two of whom had a
      t(11;18)(q21;q21) translocation, one patient had trisomies 3 and 18 and one had
      trisomy 18. CONCLUSION: Our findings suggest that CAT is found in patients with
      not only thyroidal but also nonthyroidal MALT lymphoma. While the nature of our
      data does not allow for delineation of a direct association between CAT and
      development of extrathyroidal MALT lymphoma, further prospective studies on this
      issue are warranted.

PMID- 18334511
TI  - Renal safety profiles of ibandronate 6 mg infused over 15 and 60 min: a
      randomized, open-label study.
AB  - BACKGROUND: Clinical data show that a single, 15-min i.v. infusion of ibandronate
      6 mg does not significantly alter renal function. We evaluated the effect on
      renal function of repeated 15-min infusions of ibandronate 6 mg in women with
      breast cancer and bone metastases. PATIENTS AND METHODS: Patients were randomly
      assigned to i.v. ibandronate 6 mg every 3-4 weeks for < or =6 months, infusion
      over 15 min (n = 102) or 60 min (n = 28). The primary end point was the
      percentage of patients with increased serum creatinine of > or =44.2 micromol/l.
      Blood chemistry was assessed at each visit. RESULTS: Two per cent [2/101; 95%
      confidence interval (CI) 0.2-7.0] of patients in the 15-min infusion arm and no
      patients (0/26; 95% CI 0.0-13.2) in the 60-min infusion arm had increased serum
      creatinine that met the primary end point. There were no clinically relevant
      changes in serum creatinine, creatinine clearance, or N-acetyl-beta-d
      glucosaminidase, alpha(1)-microglobulin, or microalbuminuria. Most adverse events
      were mild or moderate. No clinically relevant changes were observed in vital
      signs, hematology, blood chemistry, or urine analysis. CONCLUSIONS: Ibandronate 6
      mg by 15-min infusion every 3-4 weeks appear to be consistent with those renal
      safety profiles of 60-min infusion.

PMID- 18334512
TI  - Defining prognosis for women with breast cancer and CNS metastases by HER2
      status.
AB  - BACKGROUND: The purpose of this retrospective study was to determine, in a cohort
      of patients with breast cancer and central nervous system (CNS) metastases, the
      effect of trastuzumab in patients with human epidermal growth factor receptor 2
      (HER2)-positive disease and to compare this with that of patients with HER2
      negative disease. METHODS: Five hundred and ninety-eight patients with invasive
      breast cancer, CNS metastases and known HER2 status were identified. Time to CNS
      metastases and survival after CNS metastases were estimated by the Kaplan-Meier
      method, and Cox models were fitted to determine the association between HER2
      status, trastuzumab treatment and outcomes after adjustment for other patient
      characteristics. RESULTS: In the multivariable model, patients with HER2-negative
      disease [Hazard ratio (HR) 1.50, 95% confidence interval (CI) 1.15-1.95, P =
      0.003] and patients with HER2-positive disease who did not receive trastuzumab
      (HR 2.13, 95% CI 1.51-3.00, P < 0.0001) had shorter times to CNS metastases
      compared with patients with HER2-positive disease who had received trastuzumab as
      first-line therapy for metastases. Furthermore, patients with HER2-negative
      disease (HR 1.66, 95% CI 1.31-2.12, P < 0.0001) and patients with HER2-positive
      disease who had never received trastuzumab (HR 1.34, 95% CI 0.78-2.30, P = 0.28)
      had an increased hazard of death compared with patients with HER2-positive
      disease who had received trastuzumab before or at the time of CNS metastases
      diagnosis. CONCLUSION: In our cohort of patients with breast cancer and CNS
      metastases, patients with HER2-positive disease treated with trastuzumab had
      longer times to development of and better survival from CNS metastases compared
      with patients with HER2-positive disease who had never received trastuzumab and
      patients with HER2-negative breast cancer.

PMID- 18334513
TI  - Enhanced recombinant protein productivity by genome reduction in Bacillus
      subtilis.
AB  - The emerging field of synthetic genomics is expected to facilitate the generation
      of microorganisms with the potential to achieve a sustainable society. One
      approach towards this goal is the reduction of microbial genomes by rationally
      designed deletions to create simplified cells with predictable behavior that act
      as a platform to build in various genetic systems for specific purposes. We
      report a novel Bacillus subtilis strain, MBG874, depleted of 874 kb (20%) of the
      genomic sequence. When compared with wild-type cells, the regulatory network of
      gene expression of the mutant strain is reorganized after entry into the
      transition state due to the synergistic effect of multiple deletions, and
      productivity of extracellular cellulase and protease from transformed plasmids
      harboring the corresponding genes is remarkably enhanced. To our knowledge, this
      is the first report demonstrating that genome reduction actually contributes to
      the creation of bacterial cells with a practical application in industry. Further
      systematic analysis of changes in the transcriptional regulatory network of
      MGB874 cells in relation to protein productivity should facilitate the generation
      of improved B. subtilis cells as hosts of industrial protein production.

PMID- 18334514
TI  - Sequence level analysis of recently duplicated regions in soybean [Glycine max
      (L.) Merr.] genome.
AB  - A single recessive gene, rxp, on linkage group (LG) D2 controls bacterial leaf
      pustule resistance in soybean. We identified two homoeologous contigs (GmA and
      GmA') composed of five bacterial artificial chromosomes (BACs) during the
      selection of BAC clones around Rxp region. With the recombinant inbred line
      population from the cross of Pureunkong and Jinpumkong 2, single-nucleotide
      polymorphism and simple sequence repeat marker genotyping were able to locate
      GmA' on LG A1. On the basis of information in the Soybean Breeders Toolbox and
      our results, parts of LG A1 and LG D2 share duplicated regions. Alignment and
      annotation revealed that many homoeologous regions contained kinases and proteins
      related to signal transduction pathway. Interestingly, inserted sequences from
      GmA and GmA' had homology with transposase and integrase. Estimation of
      evolutionary events revealed that speciation of soybean from Medicago and the
      recent divergence of two soybean homoeologous regions occurred at 60 and 12
      million years ago, respectively. Distribution of synonymous substitution
      patterns, K(s), yielded a first secondary peak (mode K(s) = 0.10-0.15) followed
      by two smaller bulges were displayed between soybean homologous regions. Thus,
      diploidized paleopolyploidy of soybean genome was again supported by our study.

PMID- 18334515
TI  - Classification of mass-spectrometric data in clinical proteomics using learning
      vector quantization methods.
AB  - In the present contribution we propose two recently developed classification
      algorithms for the analysis of mass-spectrometric data-the supervised neural gas
      and the fuzzy-labeled self-organizing map. The algorithms are inherently
      regularizing, which is recommended, for these spectral data because of its high
      dimensionality and the sparseness for specific problems. The algorithms are both
      prototype-based such that the principle of characteristic representants is
      realized. This leads to an easy interpretation of the generated classifcation
      model. Further, the fuzzy-labeled self-organizing map is able to process
      uncertainty in data, and classification results can be obtained as fuzzy
      decisions. Moreover, this fuzzy classification together with the property of
      topographic mapping offers the possibility of class similarity detection, which
      can be used for class visualization. We demonstrate the power of both methods for
      two exemplary examples: the classification of bacteria (listeria types) and
      neoplastic and non-neoplastic cell populations in breast cancer tissue sections.

PMID- 18334516
TI  - Macroscopic T-wave alternans during non-sustained ventricular tachycardia.

PMID- 18334517
TI  - Targeting the poor in times of crisis: the Indonesian health card.
AB  - This paper looks at targeting performance of the Indonesian health card programme
      that was implemented in August 1998 to protect access to health care for the poor
      during the Indonesian economic crisis. By February 1999, 22 million people had
      received a health card. The health card provided a user fee waiver for public
      health care. Targeting of the health card was pro-poor, but with considerable
      leakage to the non-poor. Utilization of the health card for outpatient care was
      also pro-poor, but conditional on ownership, the middle quintiles were more
      likely to use the card. Targeting of the health card followed a decentralized
      design combining geographic targeting with community-based targeting instruments.
      This design facilitated the rapid implementation of the programme, but targeting
      performance suffered from a lack of information on the regional impact of the
      crisis, while at local level not all barriers to accessing health care services
      were overcome by the health card. Indirect and direct costs of seeking health
      care seem to be the main deterrent to using the health card, and are higher in
      more remote areas. Micro-simulations show that geographic targeting can
      contribute considerably to improving targeting performance, but most of the
      targeting gains are to be made at the local level, with district programme
      management and public health care providers. This study highlights the need for
      adequate and up-to-date social welfare indicators. In addition, further research
      would need to focus on how local knowledge can be utilized for signalling poverty
      dynamics and local barriers to access.

PMID- 18334518
TI  - Age-related macular degeneration: diagnosis and management.
AB  - BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blind
      registration in Western Europe and the third leading cause of blindness
      worldwide. METHODS: The management of AMD is discussed with a review of current
      and new treatments. RESULTS: Although there is no treatment for advanced dry AMD
      (geographic atrophy), there have been considerable advances in the management of
      neovascular AMD (nAMD). Established therapies for nAMD include laser
      photocoagulation and photodynamic therapy (PDT), but these have largely been
      superseded by agents which block the action of vascular endothelial growth factor
      (anti-VEGF agents). Current preventative strategies involve cessation of smoking
      and use of specific nutritional supplements to reduce the risk of developing
      nAMD. CONCLUSIONS: There have been exciting advances in the treatment of nAMD and
      increased understanding of the genetics and pathogenic mechanisms involved will
      hopefully lead to the development of new therapies in the future.

PMID- 18334519
TI  - Adult congenital heart disease: a 2008 overview.
AB  - INTRODUCTION: During the past decades, health care of patients born with
      congenital heart disease (CHD) has improved substantially, leading to a growing
      population of adult survivors. SOURCE OF DATA: Using the recently published and
      relevant data on adult CHD (ACHD), we reviewed the most common congenital heart
      defects and discussed important related issues. AREAS OF AGREEMENT: Adults with
      CHD most often require specialized medical or surgical care in a tertiary centre.
      However, this population also need local follow-up; general practitioners and
      other specialists therefore have to face the complexity of their disease. AREAS
      OF CONTROVERSIES: Management of pregnancy, non-cardiac surgery, arrhythmias and
      endocarditis prophylaxis may be challenging in patients with CHD and should be
      adapted to their condition. GROWING POINTS: The present article summarizes key
      clinical information on ACHD for the benefit of physicians who are not
      specialized in this field. Areas timely for developing research Research efforts
      and education strategies are greatly needed in order to optimize the care of
      patients with ACHD.

PMID- 18334520
TI  - Serotonin syndrome following cardiac surgery.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat
      depression. We report a case of serotonin syndrome following cardiac surgery.
      This syndrome is rare in the cardiac literature. The clinical features, diagnosis
      and management of this unusual syndrome are described. In patients with
      polypharmacy, it is important to take cognisance of serotonergic antidepressants
      and anticipate their potential interactions with drugs used peri-operatively.
      Early recognition and treatment is important as this condition is potentially
      fatal.

PMID- 18334521
TI  - Aortic root motion remodeling after aortic valve replacement--implications for
      late aortic dissection.
AB  - Aortic root motion was previously identified as an additional risk factor for
      aortic dissection. This study analyzed if the magnitude of aortic root motion
      changed in patients after aortic valve replacement (AVR) and acute proximal
      aortic dissection. An institutional database (1984-2005) was used to measure the
      downward motion of the aortic root (perpendicular to the plane of the sinotubular
      junction) in contrast injections in 48 patients with aortic insufficiency (AI),
      aortic stenosis (AS) and proximal aortic dissection pre- and postoperatively,
      when available. Postoperative aortic root motion was significantly reduced after
      AVR for AI, while it was significantly increased after AVR for AS. By contrast,
      aortic root motion was unchanged when functional AI due to paravalvular leak was
      present post-AVR for AI. In patients with acute aortic dissection, both aortic
      root motion and aortic diameter were unchanged from pre-dissection. However, in
      patients who dissected again, aortic root motion was significantly smaller than
      pre-dissection, and the aortic diameter was significantly less than at first
      dissection. Removal of aortic stenosis was associated with increased aortic root
      motion, theoretically heightening the threat of dissection posed to the aortic
      wall by mechanical stress, although this was not confirmed by our study of
      dissection patients. Yet, mechanical principles command to include higher
      magnitude of aortic root motion during follow-up of patients after AVR as an
      additional risk factor for dissection.

PMID- 18334522
TI  - Does re-expansion pulmonary oedema exist?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was: does re-expansion pulmonary oedema exist?
      Altogether 233 papers were found using the reported search, of which 13
      represented the best evidence to answer the clinical question. The authors,
      journal, date and country of publication, patient group studied, study type,
      relevant outcomes and results of these papers are tabulated. We conclude that re
      expansion pulmonary oedema (REPO) does occur following re-expansion of a lung in
      pneumothorax and pleural effusion. The incidence of REPO following pneumothorax
      and effusion is between 0 and 1% in most studies. The British Thoracic Society
      guidelines suggest <1.5 l pleural fluid should be drained at a time. Provided no
      respiratory symptoms occur it is not unreasonable to drain larger volumes to
      dryness: caution should be taken to avoid high negative intrapleural pressures.
      Patients who appear to be at higher risk, which may warrant more gradual
      evacuation, are: those who have had large pneumothoraces; young patients;
      patients in whom the lung has been down for >7 days; and possibly those who need
      >3 l of pleural fluid drained.

PMID- 18334523
TI  - Inhibition of osteoclasts does not prevent joint ankylosis in a mouse model of
      spondyloarthritis.
AB  - OBJECTIVES: The relationship between inflammation, destruction and new tissue
      formation leading to ankylosis, determines the severity and prognosis of patients
      with SpA. Recent data in mice and men suggest that new cartilage and bone
      formation and subsequent ankylosis are uncoupled from chronic inflammation. These
      data challenge the hypothesis that inflammation and tissue damage trigger an
      excessive repair response in SpA. We tested whether inhibition of bone erosion by
      targeting osteoclasts, would prevent or influence joint ankylosis in a mouse
      model. METHODS: Male DBA/1 mice from different litters were caged together at the
      age of 8 weeks. Treatment with zoledronic acid (ZA) (100 ng/g) or placebo was
      started at the age of 10 weeks and administered every 2 weeks. Clinical incidence
      and severity of arthritis were evaluated twice a week until the age of 26 weeks.
      At this point, bone density measurements were performed, mice were sacrificed and
      severity of arthritis was evaluated by histology. RESULTS: Treatment with ZA did
      not affect incidence or clinical severity of arthritis in male DBA/1 mice. ZA
      treatment significantly increased bone mineral density and content as
      demonstrated by dual X-ray densitometry and peripheral quantitative CT. However,
      the treatment did not affect histomorphological appearance of arthritis or
      ankylosis. CONCLUSIONS: These data suggest that bone erosion at the enthesis does
      not necessarily precede entheseal ankylosis. Therefore, these observations
      further support the concept that inflammation and new tissue formation in SpA are
      at least partially uncoupled events and may be different therapeutic targets.

PMID- 18334524
TI  - BSPAR position statement on professionals working in paediatric rheumatology.

PMID- 18334525
TI  - UK experts call for national system to evaluate diagnostic tests.

PMID- 18334526
TI  - Oral bisphosphonates and atrial fibrillation.

PMID- 18334527
TI  - Use of bisphosphonates among women and risk of atrial fibrillation and flutter:
      population based case-control study.
AB  - OBJECTIVE: To assess the association between atrial fibrillation and flutter and
      use of bisphosphonates for osteoporosis among women. DESIGN: Population based
      case-control study, using medical databases from Denmark. SETTING: Northern
      Denmark. PARTICIPANTS: 13 586 patients with atrial fibrillation and flutter and
      68 054 population controls, all with complete hospital and prescription history.
      MAIN OUTCOME MEASURE: Adjusted relative risk of atrial fibrillation and flutter.
      RESULTS: 435 cases (3.2%) and 1958 population controls (2.9%) were current users
      of bisphosphonates for osteoporosis. Etidronate and alendronate were used with
      almost the same frequency among cases and controls. The adjusted relative risk of
      current use of bisphosphonates compared with non-use was 0.95 (95% confidence
      interval 0.84 to 1.07). New users had a relative risk of 0.75 (95% confidence
      interval 0.49 to 1.16), broadly similar to the estimate for continuing users
      (relative risk 0.96, 95% confidence interval 0.85 to 1.09). The relative risk
      estimates were independent of number of prescriptions and the position of the
      atrial fibrillation and flutter diagnosis in the discharge record, and were
      similar for inpatients and outpatients. CONCLUSION: No evidence was found that
      use of bisphosphonates increases the risk of atrial fibrillation and flutter.

PMID- 18334528
TI  - Plasma adiponectin levels and clinical outcomes among haemodialysis patients.
AB  - BACKGROUND: Adiponectin (ADPN) levels are consistently elevated among patients
      with advanced chronic kidney disease, but its relationship with cardiovascular
      outcomes in this population remains controversial. METHODS: We measured baseline
      and yearly plasma ADPN in 182 prevalent haemodialysis patients recruited to the
      Haemodialysis (HEMO) Study from two Boston centres. Plasma ADPN at baseline and
      during follow-up was studied in relation to prevalent cardiovascular disease
      (CVD) and cardiovascular and all-cause mortality. RESULTS: Baseline plasma ADPN
      levels were found to be approximately twofold higher than in the general
      population and correlated inversely with (log-transformed) CRP levels and (log
      transformed) body mass index (BMI). Levels measured over time showed a gradual
      increase (0.95 microg/mL, 95% CI = 0.12-1.78 microg/mL; P = 0.03) by year,
      although this difference became non-significant after adjustment for covariates.
      Baseline ADPN levels were lower among patients with pre-existing CVD (adjusted OR
      of 0.67; P = 0.03). They also predicted all-cause mortality (P < 0.01) and the
      composite outcome of 'cardiovascular events/cardiovascular mortality' (P < 0.01);
      levels measured over time predicted the composite outcome of 'cardiovascular
      events and all-cause mortality' (P < 0.01). These relationships were non-linear
      (quadratic) with the hazard for each outcome increasing in the lower and upper
      ranges of the distribution of ADPN, and strengthened after adjustment for
      baseline covariates including serum albumin, CVD and the flux and dialysis dose
      categorization of the HEMO study. CONCLUSIONS: In summary, low plasma levels of
      ADPN were associated with inflammation and pre-existing CVD; ADPN levels
      predicted cardiovascular and mortality outcomes, the relationship being
      extensively confounded by multiple patient-related factors.

PMID- 18334529
TI  - Indoxyl sulphate promotes aortic calcification with expression of osteoblast
      specific proteins in hypertensive rats.
AB  - BACKGROUND: Stage 5 chronic kidney disease (CKD) is associated with enhanced
      aortic calcification. The aim of this study was to determine if the
      administration of indoxyl sulphate (IS), a uraemic toxin, stimulates the
      progression of aortic calcification. METHODS: The rat groups consisted of (i)
      Dahl salt-resistant normotensive rats (DR) with intake of 0.3% salt, (ii) Dahl
      salt-sensitive hypertensive rats (DS) with intake of 2.0% salt and (iii) Dahl
      salt-sensitive hypertensive IS-administered rats (DS-IS) with intake of 2.0% salt
      and 200 mg/kg of IS in water. After 30 weeks, their aortic and kidney tissues
      were excised for histological and immunohistochemical analyses. RESULTS: Severe
      vascular calcification was observed by von Kossa staining in the arcuate aorta of
      all the DS-IS rats, but hardly in DS or DR rats. Immunohistochemistry
      demonstrated that osteopontin, core binding factor 1 (Cbfal), alkaline
      phosphatase (ALP), osteocalcin, IS and organic anion transporter (OAT) 3 were
      colocalized in the cells embedded in the aortic calcification area of DS-IS rats.
      Wall thickness was significantly increased in arcuate, thoracic and abdominal
      aortas of DS-IS rats compared with DS and DR rats. DS-IS rats showed
      significantly increased extent of glomerular hypertrophy, mesangial expansion,
      Masson's trichrome-positive tubulointerstitial area and glomerular and
      tubulointerstitial expression of transforming growth factor-ssl as compared with
      DS and DR rats. CONCLUSIONS: IS induced aortic calcification with expression of
      osteoblast-specific proteins and aortic wall thickening. IS is not only a
      nephrotoxin but also a vascular toxin, and may contribute to the progression of
      aortic calcification in stage 5 CKD patients.

PMID- 18334530
TI  - wuHMM: a robust algorithm to detect DNA copy number variation using long
      oligonucleotide microarray data.
AB  - Copy number variants (CNVs) are currently defined as genomic sequences that are
      polymorphic in copy number and range in length from 1000 to several million base
      pairs. Among current array-based CNV detection platforms, long-oligonucleotide
      arrays promise the highest resolution. However, the performance of currently
      available analytical tools suffers when applied to these data because of the
      lower signal:noise ratio inherent in oligonucleotide-based hybridization assays.
      We have developed wuHMM, an algorithm for mapping CNVs from array comparative
      genomic hybridization (aCGH) platforms comprised of 385 000 to more than 3
      million probes. wuHMM is unique in that it can utilize sequence divergence
      information to reduce the false positive rate (FPR). We apply wuHMM to 385K-aCGH,
      2.1M-aCGH and 3.1M-aCGH experiments comparing the 129X1/SvJ and C57BL/6J inbred
      mouse genomes. We assess wuHMM's performance on the 385K platform by comparison
      to the higher resolution platforms and we independently validate 10 CNVs. The
      method requires no training data and is robust with respect to changes in
      algorithm parameters. At a FPR of <10%, the algorithm can detect CNVs with five
      probes on the 385K platform and three on the 2.1M and 3.1M platforms, resulting
      in effective resolutions of 24 kb, 2-5 kb and 1 kb, respectively.

PMID- 18334531
TI  - Sequence homology and microhomology dominate chromosomal double-strand break
      repair in African trypanosomes.
AB  - Genetic diversity in fungi and mammals is generated through mitotic double-strand
      break-repair (DSBR), typically involving homologous recombination (HR) or non
      homologous end joining (NHEJ). Microhomology-mediated joining appears to serve a
      subsidiary function. The African trypanosome, a divergent protozoan parasite,
      relies upon rearrangement of subtelomeric variant surface glycoprotein (VSG)
      genes to achieve antigenic variation. Evidence suggests an absence of NHEJ but
      chromosomal repair remains largely unexplored. We used a system based on I-SceI
      meganuclease and monitored temporally constrained DSBR at a specific chromosomal
      site in bloodstream form Trypanosoma brucei. In response to the lesion, adjacent
      single-stranded DNA was generated; the homologous strand-exchange factor, Rad51,
      accumulated into foci; a G(2)M checkpoint was activated and >50% of cells
      displayed successful repair. Quantitative analysis of DSBR pathways employed
      indicated that inter-chromosomal HR dominated. HR displayed a strong preference
      for the allelic template but also the capacity to interact with homologous
      sequence on heterologous chromosomes. Intra-chromosomal joining was
      predominantly, and possibly exclusively, microhomology mediated, a situation
      unique among organisms examined to date. These DSBR pathways available to T.
      brucei likely underlie patterns of antigenic variation and the evolution of the
      vast VSG gene family.

PMID- 18334532
TI  - Mitogen-induced recruitment of ERK and MSK to SRE promoter complexes by ternary
      complex factor Elk-1.
AB  - Many eukaryotic genes are acutely regulated by extra-cellular signals. The c-fos
      serum response element (SRE) mediates transcriptional activation in response to
      mitogens through serum response factor (SRF)-dependent recruitment of Elk-1, a
      mitogen-activated protein kinase (MAPK)-responsive transcription factor. How
      subsequent events at SRE promoters stimulate initiation of transcription has yet
      to be fully resolved. Here we show that extra-cellular signal-regulated kinase
      (ERK) and mitogen and stress-activated kinase (MSK) are recruited to SRE promoter
      complexes in vitro and in vivo. Their recruitment in vitro correlates with Elk-1
      binding and for ERK the D domain/KIM of Elk-1 is specifically involved. In vivo,
      recruitment of ERK and MSK is stimulated by mitogens, correlates with histone H3
      phosphorylation and is impaired by Elk-1 knockdown. Immunocytochemistry and
      confocal microscopy reveal that ERK appears to associate to some extent with
      initiating rather than elongating RNA polymerase II. Taken together, our data add
      to the body of evidence implying that ERK and related MAPKs may fulfil a generic
      role at the promoters of acutely regulated genes.

PMID- 18334533
TI  - Real-time kinetics of restriction-modification gene expression after entry into a
      new host cell.
AB  - Most type II restriction-modification (R-M) systems produce separate restriction
      endonuclease (REase) and methyltransferase (MTase) proteins. After R-M system
      genes enter a new cell, protective MTase must appear before REase to avoid host
      chromosome cleavage. The basis for this apparent temporal regulation is not well
      understood. PvuII and some other R-M systems appear to achieve this delay by
      cotranscribing the REase gene with the gene for an autogenous transcription
      activator/repressor (the 'C' protein C.PvuII). To test this model, bacteriophage
      M13 was used to introduce the PvuII genes into a bacterial population in a
      relatively synchronous manner. REase mRNA and activity appeared approximately 10
      min after those of the MTase, but never rose if there was an inactivating pvuIIC
      mutation. Infection with recombinant M13pvuII phage had little effect on cell
      growth, relative to infection with parental M13. However, infection of cells pre
      expressing C.PvuII led to cessation of growth. This study presents the first
      direct demonstration of delayed REase expression, relative to MTase, when type II
      R-M genes enter a new host cell. Surprisingly, though the C and REase genes are
      cotranscribed, the pvuIIC portion of the mRNA was more abundant than the pvuIIR
      portion after stable establishment of the R-M system.

PMID- 18334534
TI  - The small RNA GlmY acts upstream of the sRNA GlmZ in the activation of glmS
      expression and is subject to regulation by polyadenylation in Escherichia coli.
AB  - In Escherichia coli the glmS gene encoding glucosamine 6-phosphate (GlcN-6-P)
      synthase GlmS is feedback regulated by GlcN-6-P in a pathway that involves the
      small RNA GlmZ. Expression of glmS is activated by the unprocessed form of GlmZ,
      which accumulates when the intracellular GlcN-6-P concentration decreases. GlmZ
      stabilizes a glmS transcript that derives from processing. Overexpression of a
      second sRNA, GlmY, also activates glmS expression in an unknown way. Furthermore,
      mutations in two genes, yhbJ and pcnB, cause accumulation of full-length GlmZ and
      thereby activate glmS expression. The function of yhbJ is unknown and pcnB
      encodes poly(A) polymerase PAP-I known to polyadenylate and destabilize RNAs.
      Here we show that GlmY acts indirectly in a way that depends on GlmZ. When the
      intracellular GlcN-6-P concentration decreases, GlmY accumulates and causes in
      turn accumulation of full-length GlmZ, which finally activates glmS expression.
      In glmZ mutants, GlmY has no effect on glmS, whereas artificially expressed GlmZ
      can activate glmS expression also in the absence of GlmY. Furthermore, we show
      that PAP-I acts at the top of this regulatory pathway by polyadenylating and
      destabilizing GlmY. In pcnB mutants, GlmY accumulates and induces glmS expression
      by stabilizing full-length GlmZ. Hence, the data reveal a regulatory cascade
      composed of two sRNAs, which responds to GlcN-6-P and is controlled by
      polyadenylation.

PMID- 18334535
TI  - Cognitive sequencing impairment in patients with focal or atrophic cerebellar
      damage.
AB  - Although cognitive impairment after cerebellar damage has been widely reported,
      the mechanisms of cerebro-cerebellar interactions are still a matter of debate.
      The cerebellum is involved in sequence detection and production in both motor and
      sensory domains, and sequencing has been proposed as the basic mechanism of
      cerebellar functioning. Furthermore, it has been suggested that knowledge of
      sequencing mechanisms may help to define cerebellar predictive control processes.
      In spite of its recognized importance, cerebellar sequencing has seldom been
      investigated in cognitive domains. Cognitive sequencing functions are often
      analysed by means of action/script elaboration. Lesion and activation studies
      have localized this function in frontal cortex and basal ganglia circuits. The
      present study is the first to report deficits in script sequencing after
      cerebellar damage. We employed a card-sequencing test, developed ad hoc, to
      evaluate the influence of the content to be sequenced. Stimuli consisted of sets
      of sentences that described actions with a precise logical and temporal sequence
      (Verbal Factor), sets of cartoon-like drawings that reproduced behavioural
      sequences (Behavioural Factor) or abstract figures (Spatial Factor). The
      influence of the lesion characteristics was analysed by grouping patients
      according to lesion-type (focal or atrophic) and lesion-side (right or left). The
      results indicated that patients with cerebellar damage present a cognitive
      sequencing impairment independently of lesion type or localization. A correlation
      was also shown between lesion side and characteristics of the material to be
      sequenced. Namely, patients with left lesions perform defectively only on script
      sequences based on pictorial material and patients with right lesions only on
      script sequences requiring verbal elaboration. The present data support the
      hypothesis that sequence processing is the cerebellar mode of operation also in
      the cognitive domain. In addition, the presence of right/left and
      pictorial/verbal differences is in agreement with the idea that cerebro
      cerebellar interactions are organized in segregated cortico-cerebellar loops in
      which specificity is not related to the mode of functioning, but to the
      characteristics of the information processed.

PMID- 18334536
TI  - Intrinsic neuronal properties control selective targeting of regenerating
      motoneurons.
AB  - Despite advances in microsurgical techniques, recovery of motor function after
      peripheral nerve injury is often poor because many regenerating axons reinnervate
      inappropriate targets. Consequently, surgical repair must include treatment
      strategies that improve motor axon targeting. Development of such treatments will
      require a better understanding of the molecular mechanisms governing selective
      motor axon targeting. This study used a well-established model of nerve
      transection and repair to examine (1) whether intrinsic differences exist between
      different pools of motoneurons after peripheral nerve injury, (2) if such
      differences regulate selective axon targeting, (3) if regenerating motor axons
      must express polysialic acid (PSA) in order to preferentially reinnervate muscle
      and (4) whether brief electrical stimulation improves regeneration accuracy
      because it increases PSA expression on regenerating axons. We found that
      different motor pools differentially express PSA after injury and that the
      capacity to re-express PSA appears to be an intrinsic neuronal property
      established during development. Second, motoneuron pools not up-regulating PSA
      did not preferentially reinnervate muscle after injury. Third, brief electrical
      stimulation of the proximal nerve stump immediately after injury only improved
      selective motor axon targeting if the motoneurons were capable of up-regulating
      PSA. Finally, the benefits of stimulation were completely abolished if PSA was
      removed from the regenerating axons. These results indicate that (1) intrinsic
      neuronal differences between motor pools must be considered in the development of
      treatments designed to improve axon targeting and (2) therapeutics aimed at
      increasing PSA levels on regenerating motor axons may lead to superior functional
      outcomes.

PMID- 18334537
TI  - Language processing within the striatum: evidence from a PET correlation study in
      Huntington's disease.
AB  - The role of sub-cortical structures in language processing, and more specifically
      of the striatum, remains controversial. In line with psycholinguistic models
      stating that language processing implies both the recovery of lexical information
      and the application of combinatorial rules, the striatum has been claimed to be
      involved either in the former component or in the latter. The present study
      reconciles these conflicting views by showing the striatum's involvement in both
      language processes, depending on distinct striatal sub-regions. Using PET
      scanning in a model of striatal disorders, namely Huntington's disease (HD), we
      correlated metabolic data of 31 early stage HD patients regarding different
      striatal sub-regions with behavioural scores on three rule/lexicon tasks drawn
      from word morphology, syntax and from a non-linguistic domain, namely arithmetic.
      Behavioural results reflected impairment on both processing aspects, while
      deficits predominated on rule application. Both correlated with the left striatum
      but involved distinct striatal sub-regions. We suggest that the left striatum
      encompasses linguistic and arithmetic circuits, which differ with respect to
      their anatomical and functional specification, comprising ventrally located
      regions dedicated to rule computations and more dorsal portions pertaining to
      lexical devices.

PMID- 18334538
TI  - Increased CSF-BACE 1 activity is associated with ApoE-epsilon 4 genotype in
      subjects with mild cognitive impairment and Alzheimer's disease.
AB  - The Apolipoprotein (ApoE) epsilon 4 allele is a major genetic risk factor of
      Alzheimer's disease, and may affect the production of amyloid beta (A beta(1
      42)). Recently, we have shown that beta-secretase (BACE 1) activity can be
      reliably detected within the brain and human CSF. Here, we have examined an
      association between the ApoE genotype and CSF-levels of BACE 1 activity in
      Alzheimer's disease and mild cognitive impairment (MCI). A total of 148 subjects
      were included: 60 Alzheimer's disease patients, 51 MCI subjects and 37 elderly
      healthy controls. The CSF-levels of A beta(1-42), BACE 1 activity and BACE
      protein were measured in all of these subjects. The differences between ApoE
      epsilon 4 carriers and ApoE-epsilon 4 non-carriers in these CSF-based measures
      were determined controlling for gender, age and MMSE score. The ApoE-epsilon 4
      genotype was associated with increased BACE 1 activity in both Alzheimer's
      disease (P = 0.03) and MCI (P = 0.04) subjects. Levels of A beta(1-42) were
      decreased in ApoE-epsilon 4 carriers in MCI (P = 0.004) but not Alzheimer's
      disease subjects. This study is the first to demonstrate the association between
      ApoE-epsilon 4 and CSF-BACE 1 activity in MCI and Alzheimer's disease subjects.
      The assessment of BACE 1 in CSF may provide a sensitive measure to detect in vivo
      alterations in the amyloidogenic processing potentially modified by the ApoE
      genotype.

PMID- 18334540
TI  - Survival and function of human thymic dendritic cells are dependent on autocrine
      Hedgehog signaling.
AB  - The Hedgehog (Hh) family of signaling molecules functions in the development of
      numerous tissues during embryogenesis and has also been involved in adult self
      renewing tissues. Recent results have demonstrated that the different components
      of the Hh signaling pathway are expressed in the human thymus. In this study, we
      investigate whether thymic dendritic cells (DCs) are cell targets for Hh
      signaling. Both components of the Hh receptor, Patched and Smoothened, as well as
      other Hh-binding proteins with modulating functions, are expressed by human
      thymic DCs. The expression of Gli1, Gli2, and Gli3 transcription factors suggests
      that the Hh signaling pathway is active in thymic DCs, and approximately one-half
      of thymic DCs produces Sonic Hh (Shh). The culture of thymic DCs with Shh
      protects them from apoptosis [similarly to CD40 ligand (CD40L)], and these
      antiapoptotic effects are related to an up-regulation of Bcl-2 and Bcl-X(L)
      protein expression. The addition of the Hh pathway inhibitor, cyclopamine,
      decreases DC viability and impairs their allostimulatory function in vitro. In
      addition, the blockade of the Hh signaling pathway by cyclopamine treatment
      abrogates the up-regulation of HLA-DR, CD86, CD80, and CD83 expression induced by
      CD40L on thymic DCs. Finally, we also show that after activation with CD40L
      thymic DCs down-regulate the expression of Hh receptor components as well as Shh
      production. Taken together, these results suggest that the survival and function
      of thymic DCs are regulated by an autocrine Hh signaling.

PMID- 18334539
TI  - Matrix metalloproteinase-7 (matrilysin) controls neutrophil egress by generating
      chemokine gradients.
AB  - Matrilysin [matrix metalloproteinase 7 (MMP7)] is induced by mucosal injury of
      many tissues. To assess function of this proteinase, we subjected wild-type and
      Mmp7(-/-) mice to acute colon injury. When matrilysin expression was increasing,
      73% of wild-type mice died, whereas only 32% of Mmp7(-/-) mice succumbed.
      Although re-epithelialization was delayed in Mmp7(-/-) mice, overall injury did
      not differ markedly between genotypes. We hypothesized that differences in acute
      inflammation caused increased mortality in wild-type mice. Indeed, whereas
      overall neutrophil influx into tissue was similar in wild-type and Mmp7(-/-)
      mice, their location and extent of migration differed between genotypes.
      Neutrophils were dispersed throughout the mucosa and within the lumen of wild
      type mice, but these leukocytes were largely confined to the submucosa in Mmp7(-/
      ) mice. The levels of neutrophil chemokines, keratinocyte-derived chemokine and
      MIP-2, increased in the colon tissue of both genotypes, but these factors were
      detected only in lumenal lavages of wild-type mice. Our findings indicate that
      matrilysin mediates beneficial and deleterious effects in response to injury. On
      one hand, it promotes re-epithelialization, but it also controls the
      transepithelial influx of neutrophils, which if excessive, can lead to tissue
      damage.

PMID- 18334541
TI  - TGF-beta1 and IFN-gamma stimulate mouse macrophages to express BAFF via different
      signaling pathways.
AB  - B cell-activating factor belonging to the TNF family (BAFF) is primarily
      expressed by macrophages and dendritic cells and stimulates the proliferation,
      differentiation, and survival of B cells and their Ig production. In the present
      study, we examined the pathways by which TGF-beta1 and IFN-gamma induce BAFF
      expression to see if TGF-beta1 and IFN-gamma regulate B cell differentiation via
      macrophages. We found that TGF-beta1 stimulated mouse macrophages to express BAFF
      and that a typical TGF-beta signaling pathway was involved. Thus, Smad3 and Smad4
      promoted BAFF promoter activity, and Smad7 inhibited it, and the BAFF promoter
      was shown to contain three Smad-binding elements. Importantly, TGF-beta1 enhanced
      the expression of membrane-bound and soluble forms of BAFF. IFN-gamma further
      augmented TGF-beta1-induced BAFF expression. IFN-gamma caused phosphorylation of
      CREB, and overexpression of CREB increased IFN-gamma-induced BAFF promoter
      activity. Furthermore, H89, a protein kinase A (PKA) inhibitor, abrogated the
      promoter activity. Neither Stat1alpha (a well-known transducing molecule of IFN
      gamma) nor AG490 (a JAK inhibitor) affected BAFF expression in response to IFN
      gamma. Taken together, these results demonstrate that TGF-beta1 and IFN-gamma up
      regulate BAFF expression through independent mechanisms, i.e., mainly Smad3/4 and
      PKA/CREB, respectively.

PMID- 18334542
TI  - Atherogenic diet-induced hepatitis is partially dependent on murine TLR4.
AB  - Diets high in cholesterol and cholate such as the Paigen diet have been used to
      study atherogenesis, lithogenesis, and proinflammatory microvascular changes
      induced by nutritional hypercholesterolemia. Although these diets lead to chronic
      hepatic inflammation and fibrosis, the early inflammatory changes have been
      poorly characterized. TLR4, a known receptor for LPS, is also a receptor for a
      variety of endogenous ligands and has been implicated in atheroma formation.
      Here, we specifically examined the early inflammatory response of the liver to
      the atherogenic (ATH) diet and the possible contribution of TLR4. Animals fed the
      high-cholesterol/cholate diet for 3 weeks developed a significant, predominantly
      mononuclear leukocyte infiltration in the liver, hepatic steatosis, elevated
      hepatic expression of MCP-1, RANTES, and MIP-2, and increased serum levels of
      liver enzymes. In TLR4-deleted animals, there was a 30% attenuation in the serum
      alanine transaminase levels and a 50% reduction in the leukocyte infiltration
      with a fourfold reduction in chemokine expression. In contrast, hepatic steatosis
      did not differ from wild-type controls. TLR2 deletion had no effect on diet
      induced hepatitis but increased the amount of steatosis. We conclude that the
      early inflammatory liver injury but not hepatic lipid loading induced by the ATH
      diet in mice is mediated in part by TLR4.

PMID- 18334543
TI  - Validation process and uncertainty budget: a recommended approach for performance
      verification.
AB  - Within its Occupational Radiation Protection Programme, the International Atomic
      Energy Agency (IAEA) initiated and funded many international and regional
      intercomparison exercises, with the aim of verifying performance of the
      individual monitoring service providers. An important component within the
      quality system is the validation and uncertainty budget of the method used. Each
      method must be validated. This validation process must provide evidence that the
      method can fulfil all requirements for its intended use. A method may be regarded
      as validated only when it fulfils all requirements established before the
      validation process. This paper reviews methods recommended for different types of
      measurement techniques in individual monitoring.

PMID- 18334544
TI  - Intercomparison on measurements of the quantity personal dose equivalent Hp(d) in
      mixed (neutron-gamma) fields--an IAEA project.
AB  - Within its occupational radiation protection programme, the International Atomic
      Energy Agency (IAEA) initiated and funded an international intercomparison
      exercise of personal dosemeters to determine the quantity personal dose
      equivalent in mixed neutron-photon radiation. The objectives of the
      intercomparison are to assess the capabilities of the dosimetry services in
      measuring the quantity Hp(10) in mixed neutron-gamma fields; to assist IAEA
      member states in achieving sufficiently accurate dosimetry; and, if necessary, to
      provide guidelines for improvements (not simply a test of the performance of the
      existing dosimetry service). The intercomparison is directed to passive
      dosemeters to determine, in mixed neutron-gamma radiation fields, either these
      two components separately or the total personal dose equivalent. The
      intercomparison consists of two phases: Phase I--Type-test intercomparison:
      irradiation in selected calibration fields and results used to improve dosimetric
      procedures of participating laboratories, where needed. Phase II--Simulated
      workplace field intercomparison: irradiation in radiation fields similar to those
      in workplaces as a final check of performance. The exercise revealed clear
      deficiencies in the methodology used by several laboratories and necessitated a
      detailed analysis of the existing discrepancies. This papers summaries the
      finding and conclusions for radiation fields similar to those found in nuclear
      industry.

PMID- 18334546
TI  - Ischaemic postconditioning protects isolated mouse hearts against
      ischaemia/reperfusion injury via sphingosine kinase isoform-1 activation.
AB  - AIMS: Sphingosine-1-phosphate (S1P) plays a vital role in cytoskeletal
      rearrangement, development, and apoptosis. Sphingosine kinase-1 (SphK1), the key
      enzyme catalyzing the formation of S1P, mediates ischaemic preconditioning.
      Ischaemic postconditioning (POST) has been shown to protect hearts against
      ischaemia/reperfusion injury (IR). To date, no studies have examined the role of
      SphK1 in POST. METHODS AND RESULTS: Wild-type (WT) and SphK1 null (KO) mouse
      hearts were subjected to IR (45 min of global ischaemia and 45 min of
      reperfusion) in a Langendorff apparatus. Left ventricular developed pressure
      (LVDP), maximum velocity of increase or decrease of LV pressure (+/-dP/dtmax),
      and LV end-diastolic pressure (LVEDP) were recorded. Infarction size was measured
      by 1% triphenyltetrazolium chloride staining. POST, consisting of 5 s of
      ischaemia and 5 s of reperfusion for three cycles after the index ischaemia,
      protected hearts against IR: recovery of LVDP and +/-dP/dtmax were elevated;
      LVEDP was decreased; infarction size (% of risk area) was reduced from 40 +/- 2%
      in the control group to 29 +/- 2% of the risk area in the POST group (P < 0.05, n
      = 4 per group). Phosphorylation of Akt and extracellular signal-regulated kinases
      detected by Western blotting was increased at 10 min of reperfusion. The
      protection induced by POST was abolished in KO hearts. Infarction size in KO
      hearts (57 +/- 5%) was not different from the KO control group (53 +/- 5% of risk
      area, n = 4, P = NS). CONCLUSIONS: A short period of ischaemic POST protected WT
      mouse hearts against IR. The cardiac protection induced by POST was abrogated in
      SphK1-KO mouse hearts. Thus, SphK1 is critical for successful ischaemic POST.

PMID- 18334547
TI  - Cardiac-directed parvalbumin transgene expression in mice shows marked heart rate
      dependence of delayed Ca2+ buffering action.
AB  - Relaxation abnormalities are prevalent in heart failure and contribute to
      clinical outcomes. Disruption of Ca2+ homeostasis in heart failure delays
      relaxation by prolonging the intracellular Ca2+ transient. We sought to speed
      cardiac relaxation in vivo by cardiac-directed transgene expression of
      parvalbumin (Parv), a cytosolic Ca2+ buffer normally expressed in fast-twitch
      skeletal muscle. A key feature of Parv's function resides in its Ca2+/Mg2+
      binding affinities that account for delayed Ca2+ buffering in response to the
      intracellular Ca2+ transient. Cardiac Parv expression decreased sarcoplasmic
      reticulum Ca2+ content without otherwise altering intracellular Ca2+ homeostasis.
      At high physiological mouse heart rates in vivo, Parv modestly accelerated
      relaxation without affecting cardiac morphology or systolic function. Ex vivo
      pacing of the isolated heart revealed a marked heart rate dependence of Parv's
      delayed Ca2+ buffering effects on myocardial performance. As the pacing frequency
      was lowered (7 to 2.5 Hz), the relaxation rates increased in Parv hearts.
      However, as pacing rates approached the dynamic range in humans, Parv hearts
      demonstrated decreased contractility, consistent with Parv buffering systolic
      Ca2+. Mathematical modeling and in vitro studies provide the underlying mechanism
      responsible for the frequency-dependent fractional Ca2+ buffering action of Parv.
      Future studies directed toward refining the dose and frequency-response
      relationships of Parv in the heart or engineering novel Parv-based Ca2+ buffers
      with modified Mg2+ and Ca2+ affinities to limit systolic Ca2+ buffering may hold
      promise for the development of new therapies to remediate relaxation
      abnormalities in heart failure.

PMID- 18334548
TI  - Systematic assessment of the human osteoblast transcriptome in resting and
      induced primary cells.
AB  - Osteoblasts are key players in bone remodeling. The accessibility of human
      primary osteoblast-like cells (HObs) from bone explants makes them a lucrative
      model for studying molecular physiology of bone turnover, for discovering novel
      anabolic therapeutics, and for mesenchymal cell biology in general. Relatively
      little is known about resting and dynamic expression profiles of HObs, and to
      date no studies have been conducted to systematically assess the osteoblast
      transcriptome. The aim of this study was to characterize HObs and investigate
      signaling cascades and gene networks with genomewide expression profiling in
      resting and bone morphogenic protein (BMP)-2- and dexamethasone-induced cells. In
      addition, we compared HOb gene expression with publicly available samples from
      the Gene Expression Omnibus. Our data show a vast number of genes and networks
      expressed predominantly in HObs compared with closely related cells such as
      fibroblasts or chondrocytes. For instance, genes in the insulin-like growth
      factor (IGF) signaling pathway were enriched in HObs (P = 0.003) and included the
      binding proteins (IGFBP-1, -2, -5) and IGF-II and its receptor. Another HOb
      specific expression pattern included leptin and its receptor (P < 10(-8)).
      Furthermore, after stimulation of HObs with BMP-2 or dexamethasone, the
      expression of several interesting genes and pathways was observed. For instance,
      our data support the role of peripheral leptin signaling in bone cell function.
      In conclusion, we provide the landscape of tissue-specific and dynamic gene
      expression in HObs. This resource will allow utilization of osteoblasts as a
      model to study specific gene networks and gene families related to human bone
      physiology and diseases.

PMID- 18334549
TI  - Differential trafficking of Kif5c on tyrosinated and detyrosinated microtubules
      in live cells.
AB  - Kinesin-1 is a molecular transporter that trafficks along microtubules. There is
      some evidence that kinesin-1 targets specific cellular sites, but it is unclear
      how this spatial regulation is achieved. To investigate this process, we used a
      combination of in vivo imaging of kinesin heavy-chain Kif5c (an isoform of
      kinesin-1) fused to GFP, in vitro analyses and mathematical modelling. GFP-Kif5c
      fluorescent puncta localised to a subset of microtubules in live cells. These
      puncta moved at speeds of up to 1 microm second(-1) and exchanged into cortically
      labelled clusters at microtubule ends. This behaviour depended on the presence of
      a functional motor domain, because a rigor-mutant GFP-Kif5c bound to microtubules
      but did not move along them. Further analysis indicated that the microtubule
      subset decorated by GFP-Kif5c was highly stable and primarily composed of
      detyrosinated tubulin. In vitro motility assays showed that the motor domain of
      Kif5c moved detyrosinated microtubules at significantly lower velocities than
      tyrosinated (unmodified) microtubules. Mathematical modelling predicted that a
      small increase in detyrosination would bias kinesin-1 occupancy towards
      detyrosinated microtubules. These data suggest that kinesin-1 preferentially
      binds to and trafficks on detyrosinated microtubules in vivo, providing a
      potential basis for the spatial targeting of kinesin-1-based cargo transport.

PMID- 18334550
TI  - The facultative heterochromatin of the inactive X chromosome has a distinctive
      condensed ultrastructure.
AB  - The mammalian inactive X chromosome (Xi) is a model for facultative
      heterochromatin. Increased DNA compaction for the Xi, and for facultative
      heterochromatin in general, has long been assumed based on recognition of a
      distinct Barr body using nucleic-acid staining. This conclusion has been
      challenged by a report revealing equal volumes occupied by the inactive and
      active X chromosomes. Here, we use light and electron microscopy to demonstrate
      in mouse and human fibroblasts a unique Xi ultrastructure, distinct from
      euchromatin and constitutive heterochromatin, containing tightly packed,
      heterochromatic fibers/domains with diameters in some cases approaching that of
      prophase chromatids. Significant space between these packed structures is
      observed even within condensed regions of the Xi. Serial-section analysis also
      reveals extensive contacts of the Xi with the nuclear envelope and/or nucleolus,
      with nuclear envelope association being observed in all cells. Implications of
      our results for models of Xi gene silencing and chromosome territory organization
      are discussed.

PMID- 18334551
TI  - Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for
      phosphoinositides in flagellar biogenesis.
AB  - Axonemes are microtubule-based organelles of crucial importance in the structure
      and function of eukaryotic cilia and flagella. Despite great progress in
      understanding how axonemes are assembled, the signals that initiate axoneme
      outgrowth remain unknown. Here, we identified phosphatidylinositol phosphates
      (phosphoinositides) as key regulators of early stages of axoneme outgrowth in
      Drosophila melanogaster spermatogenesis. In a study of phosphatidylinositol 4,5
      bisphosphate [PtdIns(4,5)P2] function in developing Drosophila male germ cells,
      we depleted PtdIns(4,5)P2 by expression of a potent phosphoinositide phosphatase.
      Phosphatase expression dramatically inhibited sperm tail formation and perturbed
      microtubule organization in a manner reversible by co-expression of a PtdIns 4
      phosphate 5-kinase. Depletion of PtdIns(4,5)P2 caused increased levels of basal
      body gamma-tubulin and altered the distribution of proteins known to be required
      for axoneme assembly. Examination of PtdIns(4,5)P2-depleted spermatids by
      transmission electron microscopy revealed defects in basal body docking to the
      nuclear envelope, and in axoneme architecture and integrity of the developing
      flagellar axoneme and axial sheath. Our results provide the first evidence that
      phosphoinositides act at several steps during flagellar biogenesis, coordinately
      regulating microtubule and membrane organization. They further suggest that
      phosphoinositides play evolutionarily conserved roles in flagella and cilia,
      across phyla and in structurally diverse cell types.

PMID- 18334552
TI  - Targeted transgenic expression of the mutation causing Hutchinson-Gilford
      progeria syndrome leads to proliferative and degenerative epidermal disease.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare human genetic disorder
      characterized by striking progeroid features. Clinical findings in the skin
      include scleroderma, alopecia and loss of subcutaneous fat. HGPS is usually
      caused by a dominant-negative mutation in LMNA, a gene that encodes two major
      proteins of the inner nuclear lamina: lamin A and lamin C. We have generated
      tetracycline-inducible transgenic lines that carry a minigene of human LMNA under
      the control of a tet-operon. Two mouse lines were created: one carrying the wild
      type sequence of LMNA and the other carrying the most common HGPS mutation.
      Targeted expression of the HGPS mutation in keratin-5-expressing tissues led to
      abnormalities in the skin and teeth, including fibrosis, loss of hypodermal
      adipocytes, structural defects in the hair follicles and sebaceous glands, and
      abnormal incisors. The severity of the defects was related to the level of
      expression of the transgene in different mouse lines. These transgenic mice
      appear to be good models for studies of the molecular mechanisms of skin
      abnormalities in HGPS and other related disorders.

PMID- 18334553
TI  - Dictyostelium MEGAPs: F-BAR domain proteins that regulate motility and membrane
      tubulation in contractile vacuoles.
AB  - PCH family proteins are fundamentally important proteins, linking membrane
      curvature events with cytoskeletal reorganisation. One group, the MEGAPs (also
      called srGAPs and WRPs) contain RhoGAP domains in addition to the F-BAR domain.
      We disrupted MEGAP1 and MEGAP2 in Dictyostelium both singly and in combination.
      We found a strong cytoskeletal phenotype in MEGAP1(-) cells and a subtle
      phototaxis defect in MEGAP2(-) slugs. MEGAP1(-)/2(-) cells have an overabundance
      of filopodia and slug motility and function are affected. The most dramatic
      changes, however, are on contractile vacuoles. MEGAP1(-)/2(-) cells empty their
      contractile vacuoles less efficiently than normal and consequently have three
      times the usual number. GFP-tagged MEGAP1 localises to tubules of the contractile
      vacuole network and when vacuoles start to empty they recruit cytosolic GFP
      MEGAP1. Mutants in the Saccharomyces homologues RGD1 and RGD2 also show abnormal
      vacuoles, implying that this role is conserved. Thus, MEGAP is an important
      regulator of the contractile vacuole network, and we propose that tubulation of
      the contractile vacuole by MEGAP1 represents a novel mechanism for driving
      vacuole emptying.

PMID- 18334554
TI  - The integrity of a lamin-B1-dependent nucleoskeleton is a fundamental determinant
      of RNA synthesis in human cells.
AB  - Spatial organisation of nuclear compartments is an important regulator of
      chromatin function, yet the molecular principles that maintain nuclear
      architecture remain ill-defined. We have used RNA interference to deplete key
      structural nuclear proteins, the nuclear lamins. In HeLa cells, we show that
      reduced expression of lamin B1, but not lamin A/C, severely inhibits RNA
      synthesis--first by RNA polymerase II and later by RNA polymerase I. Declining
      levels of transcription correlate with different morphological changes in major
      nuclear compartments, nucleoli and nuclear speckles. Ultimately, nuclear changes
      linked to the loss of synthetic activity result in expansion of the inter
      chromatin domain and corresponding changes in the structure and spatial
      organisation of chromosome territories, which relocate towards the nuclear
      periphery. These results show that a lamin B1-containing nucleoskeleton is
      required to maintain RNA synthesis and that ongoing synthesis is a fundamental
      determinant of global nuclear architecture in mammalian cells.

PMID- 18334555
TI  - PGE2-mediated podosome loss in dendritic cells is dependent on actomyosin
      contraction downstream of the RhoA-Rho-kinase axis.
AB  - Podosomes are dynamic adhesion structures found in dendritic cells (DCs) and
      other cells of the myeloid lineage. We previously showed that prostaglandin E2
      (PGE2), an important proinflammatory mediator produced during DC maturation,
      induces podosome disassembly within minutes after stimulation. Here, we
      demonstrate that this response is mediated by cAMP elevation, occurs downstream
      of Rho kinase and is dependent on myosin II. Whereas PGE2 stimulation leads to
      activation of the small GTPase RhoA, decreased levels of Rac1-GTP and Cdc42-GTP
      are observed. These results show that PGE2 stimulation leads to activation of the
      RhoA-Rho-kinase axis to promote actomyosin-based contraction and subsequent
      podosome dissolution. Because podosome disassembly is accompanied by de novo
      formation of focal adhesions, we propose that the disassembly/formation of these
      two different adhesion structures is oppositely regulated by actomyosin
      contractility and relative activities of RhoA, Rac1 and Cdc42.

PMID- 18334556
TI  - Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by
      TGF-beta1.
AB  - Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the
      pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal
      transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal
      kinase (JNK) has been demonstrated, the goal of this study was to elucidate
      whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse
      tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were
      comparatively evaluated for their ability to undergo EMT in response to TGF
      beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of
      mesenchymal mediators and a loss of epithelial markers, in conjunction with a
      loss of trans-epithelial resistance (TER). Significantly, TGF-beta1-mediated EMT
      was markedly blunted in epithelial cells lacking JNK1, while JNK2-/- MTEC
      underwent EMT in response to TGF-beta1 in a similar way to wild-type cells.
      Although Smad2/3 phosphorylation and nuclear localization of Smad4 were similar
      in JNK1-/- MTEC in response to TGF-beta1, Smad DNA-binding activity was
      diminished. Gene expression profiling demonstrated a global suppression of TGF
      beta1-modulated genes, including regulators of EMT in JNK1-/- MTEC, in comparison
      with wild-type cells. In aggregate, these results illuminate the novel role of
      airway epithelial-dependent JNK1 activation in EMT.

PMID- 18334557
TI  - Telomerase does not counteract telomere shortening but protects mitochondrial
      function under oxidative stress.
AB  - Telomerase is a ribonucleoprotein that counteracts telomere shortening and can
      immortalise human cells. There is also evidence for a telomere-independent
      survival function of telomerase. However, its mechanism is not understood. We
      show here that TERT, the catalytic subunit of human telomerase, protects human
      fibroblasts against oxidative stress. While TERT maintains telomere length under
      standard conditions, telomeres under increased stress shorten as fast as in cells
      without active telomerase. This is because TERT is reversibly excluded from the
      nucleus under stress in a dose- and time-dependent manner. Extranuclear
      telomerase colocalises with mitochondria. In TERT-overexpressing cells, mtDNA is
      protected, mitochondrial membrane potential is increased and mitochondrial
      superoxide production and cell peroxide levels are decreased, all indicating
      improved mitochondrial function and diminished retrograde response. We propose
      protection of mitochondria under mild stress as a novel function of TERT.

PMID- 18334559
TI  - The function of two closely related Rho proteins is determined by an atypical
      switch I region.
AB  - We show here that the encoded proteins of the two duplicated RHO1 genes from the
      filamentous fungus Ashbya gossypii, AgRHO1a and AgRHO1b have functionally
      diverged by unusual mutation of the conserved switch I region. Interaction
      studies and in vitro assays suggest that a different regulation by the two GTPase
      activating proteins (GAPs) AgLrg1 and AgSac7 contributes to the functional
      differences. GAP-specificity and protein function is determined to a large part
      by a single position in the switch I region of the two Rho1 proteins. In AgRho1b,
      this residue is a tyrosine that is conserved among the Rho-protein family,
      whereas AgRho1a carries an atypical histidine at the same position. Mutation of
      this histidine to a tyrosine changes GAP-specificity, protein function and
      localization of AgRho1a. Furthermore, it enables the mutated allele to complement
      the lethality of an AgRHO1b deletion. In summary, our findings show that a simple
      mutation in the switch I region of a GTP-binding protein can change its affinity
      towards its GAPs, which finally leads to a decoupling of very similar protein
      function without impairing effector interaction.

PMID- 18334558
TI  - Analysis of protein domains and Rett syndrome mutations indicate that multiple
      regions influence chromatin-binding dynamics of the chromatin-associated protein
      MECP2 in vivo.
AB  - The methyl-CpG-binding protein 2 (MECP2) serves both organizational and
      transcriptional functions in the nucleus, with two well-characterized domains
      integrally related to these functions. The recognition of methylated CpG
      dinucleotides is accomplished by the methyl-binding domain (MBD), and the
      transcriptional repression domain (TRD) facilitates protein-protein interactions
      with chromatin remodeling proteins. For each known function of MECP2, chromatin
      binding is a crucial activity. Here, we apply photobleaching strategies within
      the nucleus using domain-deleted MECP2 proteins as well as naturally occurring
      point mutations identified in individuals with the neurodevelopmental disorder
      Rett syndrome (RTT). These studies reveal that MECP2 is transiently associated
      with chromatin in vivo and confirm a central role for the MBD in directing the
      protein to heterochromatin. In addition, we report for the first time that the
      small region between the MBD and the TRD, known as the interdomain region (ID),
      stabilizes chromatin binding by MECP2 independently of the MBD. The TRD of MECP2
      also contributes towards chromatin binding, whereas the N- and C-termini do not.
      Some common RTT missense and nonsense mutations significantly affect binding
      kinetics, suggesting that alterations in chromatin binding can result in protein
      dysfunction and hence a disease phenotype.

PMID- 18334560
TI  - Epithelial cell-cell contacts regulate SRF-mediated transcription via Rac-actin
      MAL signalling.
AB  - Epithelial cell-cell junctions are specialised structures connecting individual
      cells in epithelial tissues. They are dynamically and functionally linked to the
      actin cytoskeleton. Disassembly of these junctions is a key event during
      physiological and pathological processes, but how this influences gene expression
      is largely uncharacterised. Here, we investigate whether junction disassembly
      regulates transcription by serum response factor (SRF) and its coactivator
      MAL/MRTF. Ca2+-dependent dissociation of epithelial integrity was found to
      correlate strictly with SRF-mediated transcription. In cells lacking E-cadherin
      expression, no SRF activation was observed. Direct evidence is provided that
      signalling occurs via monomeric actin and MAL. Dissociation of epithelial
      junctions is accompanied by induction of RhoA and Rac1. However, using
      clostridial cytotoxins, we demonstrate that Rac, but not RhoA, is required for
      SRF and target gene induction in epithelial cells, in contrast to serum
      stimulated fibroblasts. Actomyosin contractility is a prerequisite for signalling
      but failed to induce SRF activation, excluding a sufficient role of the Rho-ROCK
      actomyosin pathway. We conclude that E-cadherin-dependent cell-cell junctions
      facilitate transcriptional activation via Rac, G-actin, MAL and SRF upon
      epithelial disintegration.

PMID- 18334561
TI  - Teaching calcium-induced calcium release in cardiomyocytes using a classic paper
      by Fabiato.
AB  - This teaching paper utilizes the materials presented by Dr. Fabiato in his review
      article entitled "Calcium-induced release of calcium from the cardiac
      sarcoplasmic reticulum." In the review, supporting evidence of calcium-induced
      calcium release (CICR) is presented. Data concerning potential objections to the
      CICR theory are discussed as well. In closing, technical issues associated with
      the skinned cell model are mentioned. Based on this review article, teaching and
      learning points are put forth in this article to highlight two concepts: 1) the
      regulatory mechanisms of CICR in cardiomyocytes and 2) the recognition of
      contradicting hypotheses and limitations in experimental design. The first
      concept is certainly an important one for physiology students. The second concept
      is universally applicable to researchers in all fields of science. It is thus the
      aim of this article to cultivate a rewarding teaching and learning experience for
      both instructors and students.

PMID- 18334562
TI  - Teaching the physiology of adaptation to hypoxic stress with the aid of a classic
      paper on high altitude by Houston and Riley.
AB  - Many pathological conditions exist where tissues exhibit hypoxia or low oxygen
      tension. Hypoxic hypoxia arises when there is a reduction in the amount of oxygen
      entering the blood and occurs in healthy people at high altitude. In 1946,
      research sponsored by the United States Navy led to the collection and subsequent
      publication of masses of data demonstrating the physiological consequences and
      adaptations of ascent to high altitude. This article describes how a figure from
      a 1947 paper from the American Physiological Society Legacy collection (Houston
      CS, Riley RL. Respiratory and circulatory changes during acclimatization to high
      altitude. Am J Physiol 149: 565-588) may be used to allow students to review
      their understanding of some of the generalized effects of hypoxia on the body. In
      particular, this figure summarizes some of the adaptive responses that take place
      in the oxygen transport system as a consequence of prolonged hypoxia.

PMID- 18334563
TI  - Teaching the interrelationship between stress, emotions, and cardiovascular risk
      using a classic paper by Walter Cannon.
AB  - Classroom discussion of the classic article by Walter B. Cannon in 1914, entitled
      "The emergency function of the adrenal medulla in pain and the major emotions,"
      is an excellent tool to teach graduate students the interaction between stress,
      emotions, and cardiovascular function. Using this article, we are able to review
      important early research by Dr. Cannon, including discussion of his scientific
      methods and results and how they hold true today. This article outlines how this
      classic paper is used to allow students to explore basics principles of
      cardiovascular control during stress. The teaching points that are presented
      illustrate how students can be directed to understand the interrelationship
      between chronic stress and cardiovascular disease.

PMID- 18334564
TI  - Don't dump the didactic lecture; fix it.
AB  - Numerous articles have been published on the merits of active learning, and
      collectively they present a body of compelling evidence that these methods do
      enhance learning. In presenting arguments for active learning, it is often
      suggested that the traditional didactic lecture is more passive in nature and
      less effective as a teaching tool. However, a well organized lecture remains one
      of the most effective ways to integrate and present information from multiple
      sources on complex topics, such as those encountered in the teaching of
      physiology. This article presents an argument for enhancing lectures by
      incorporating active learning activities within their framework, and it is noted
      that engagement of the student is a key element making active learning activities
      work. Finally, suggestions are provided on the basis of the author's experience
      of things instructors can do to make lecture-based courses more engaging to
      students and, hence, promote learning.

PMID- 18334565
TI  - New ways of thinking about (and teaching about) intestinal epithelial function.
AB  - This article summarizes a presentation made at the Teaching Refresher Course of
      the American Physiological Society, which was held at the Experimental Biology
      meeting in 2007. The intestinal epithelium has important ion transport and
      barrier functions that contribute pivotally to normal physiological functioning
      of the intestine and other body systems. These functions are also frequently the
      target of dysfunction that, in turn, results in specific digestive disease
      states, such as diarrheal illnesses. Three emerging concepts are discussed with
      respect to ion transport: the complex interplay of intracellular signals that
      both activate and inhibit chloride secretion; the role of multiprotein complexes
      in the regulation of ion transport, taking sodium/hydrogen exchange as an
      example; and acute and chronic regulation of colonic sodium absorption, involving
      both sodium channel internalization and de novo synthesis of new channels.
      Similarly, recently obtained information about the molecular components of
      epithelial tight junctions and the ways in which tight junctions are regulated
      both in health and disease are discussed to exemplify ways to teach about
      intestinal barrier properties. Finally, both genetically determined intestinal
      diseases and those arising as a result of infections and/or inflammation are
      described, and these can be used as the means to enhance the basic and clinical
      relevance of teaching about intestinal epithelial physiology as well as the
      impact that the understanding of such physiology has had on associated
      therapeutics. The article also indicates, where relevant, how different
      approaches may be used effectively to teach related concepts to graduate versus
      medical/professional student audiences.

PMID- 18334566
TI  - Learning approaches of undergraduate medical students to physiology in a non-PBL-
      and partially PBL-oriented curriculum.
AB  - Melaka Manipal Medical College (Manipal Campus; Manipal, Karnataka, India)
      conducts the Bachelor of Medicine and Bachelor of Surgery program, for which the
      admission intakes are during the months of March and September. The present study
      was undertaken to study the differences in learning approaches to physiology of
      undergraduate medical students in a partially problem-based learning (PBL)- and
      non-PBL-oriented curriculum. PBL was introduced as a curricular reform for the
      September 2006 batch of students (partially PBL group), whereas it was not
      incorporated for the March 2006 batch of students (non-PBL group). Learning
      approaches to physiology of both groups of students were compared using the short
      inventory of approaches to learning. Mean scores for deep and strategic
      approaches were found to be significantly higher for the partially PBL group
      compared with the non-PBL group. The results of the present study support the
      earlier observation that PBL promotes a deep approach to learning.

PMID- 18334567
TI  - The use of multiple tools for teaching medical biochemistry.
AB  - In this work, we describe the use of several strategies employing the
      philosophies of active learning and problem-based learning (PBL) that may be used
      to improve the teaching of metabolic biochemistry to medical and nutritional
      undergraduate students. The main activities are as follows: 1) a seminar/poster
      system in a mini-congress format (using topics of applied biochemistry); 2) a
      true/false applied biochemistry exam (written by peer tutors); 3) a 9-h exam on
      metabolism (based in real publications); 4) the Advanced Biochemistry course
      (directed to peer tutors, where students learn how to read and criticize real
      medical papers); 5) experiments about nutrition and metabolism, using students as
      volunteers, and about free radicals (real science for students); 6) the BioBio
      blog (taking advantage of the "web age," this enhances out of class exchanges of
      information between the professor, students, and peer tutors); 7) student
      lectures on public health issues and metabolic disorders directed to the
      community and lay people; and 8) the BioBio quiz show. The main objective of
      these activities is to provide students with a more practical and interesting
      approach to biochemistry, such as the application of theoretical knowledge to
      real situations (diseases, experiments, media information, and scientific
      discoveries). In addition, we emphasize the importance of peer tutor activities
      for optimized learning of both students and peer tutors, the importance of a
      closer interaction between students and teaching staff, and the necessity to
      initiate students precociously in two broad fields of medical activity: "real"
      basic science and contact with the public (also helping students--future doctors
      and nutritionists--to be able to communicate with lay people). Most activities
      were evaluated by the students through written questionnaires and informal
      conversations, along various semesters, indicating good acceptance and approval
      of these methods. Good student scores in the biochemistry exams and seminars
      indicated that these activities are also working as valid educational tools.

PMID- 18334568
TI  - Student perceptions and use of an assessment rubric for a group concept map in
      physiology.
AB  - We previously reported how the opinions of second-year dentistry students and
      faculty members can be used to construct an assessment rubric to grade group
      based concept maps in physiology. This article describes the second phase of this
      study of the subsequent year's cohort. A case study approach was used to
      investigate how groups of students used the criteria to complete their complex
      concept maps. Students' opinions about the assessment task and newly constructed
      rubric were sampled. Opinions across groups were correlated to academic
      achievements in the course. Two groups of four students volunteered to be
      videorecorded during a 4-h workshop, during which they completed their maps. The
      mapping task was not generally favored by students. However, those students who
      did favor the task achieved higher academic grades. Most students favored the
      newly constructed assessment rubric, commenting that it was easy to understand,
      fair, and appropriate, but reported that extra guidance from tutors and other
      resources were required. Coded videorecordings of the two observation groups
      revealed complex interactions around the three criteria of content, logic and
      understanding, and presentation. Two broad patterns of working were identified.
      One group distributed their efforts more evenly across the criteria, whereas the
      other group completed their maps by addressing the criteria in stages. These
      findings clearly indicate the academic challenges and social complexity in how
      students work in groups to complete complex concept maps in physiology.

PMID- 18334569
TI  - Blood circulation laboratory investigations with video are less investigative
      than instructional blood circulation laboratories with live organisms.
AB  - Live organisms versus digital video of the organisms were used to challenge
      students' naive ideas and misconceptions about blood, the heart, and circulatory
      patterns. Three faculty members taught 259 grade 10 biology students in a
      California high school with students from diverse ethnolinguistic groups who were
      divided into 5 classes using microscopes (128 students) and 5 classes using
      digital video (131 students) to compare blood transport among invertebrates,
      fish, and humans. The "What Is Happening in this Class?" (WIHIC) questionnaire
      was used for assessment of microscope and video groups to detect students'
      perception of their learning environment following these teaching interventions.
      The use of microscopes had a clear effect on the perception of the investigative
      aspects of the learning environment that was not detected with the video
      treatment. Findings suggest that video should not replace investigations with
      live organisms.

PMID- 18334570
TI  - Teaching pulmonary gas exchange physiology using computer modeling.
AB  - Students often have difficulty understanding the relationship of O(2)
      consumption, CO(2) production, cardiac output, and distribution of ventilation
      perfusion ratios in the lung to the final arterial blood gas composition. To
      overcome this difficulty, I have developed an interactive computer simulation of
      pulmonary gas exchange that is web based and allows the student to vary multiple
      factors simultaneously and observe the final effect on the arterial blood gas
      composition (available at www.siumed.edu/medicine/pulm/vqmodeling.htm). In this
      article, the underlying mathematics of the computer model is presented, as is the
      teaching strategy. The simulation is applied to a typical clinical case drawn
      from the intensive care unit to demonstrate the interdependence of the above
      factors as well as the less-appreciated importance of the Bohr and Haldane
      effects in clinical pulmonary medicine. The use of a computer to vary the many
      interacting factors involved in the arterial blood gas composition appeals to
      today's students and demonstrates the importance of basic physiology to the
      actual practice of medicine.

PMID- 18334571
TI  - A blended approach to active learning in a physiology laboratory-based subject
      facilitated by an e-learning component.
AB  - Learning via online activities (e-learning) was introduced to facilitate existing
      face-to-face teaching to encourage more effective student preparation and then
      informed participation in an undergraduate physiology laboratory-based course.
      Active learning was encouraged by hypothesis formation and predictions prior to
      classes, with opportunities for students to amend their e-learning submissions
      after classes. Automatic or tutor feedback was provided on student submissions.
      Evaluation of the course was conducted via student questionnaires, individual
      student interviews, and analysis of student marks in examinations and of the e
      learning component. Student feedback on this entire subject in the university
      wide quality of teaching survey was very high by University of Melbourne
      standards and most encouraging for the first implementation of such a curriculum
      modification. Results from further detailed surveys of student interactions and
      engagement and correlation analysis between student responses were also very
      supportive of the effectiveness of the course. There were no significant
      differences between examination marks in the new course with e-learning and the
      previous year without e-learning. However, there was a significant correlation
      between assessment of student e-learning work and their final examination mark.
      Correlation analysis between various survey responses helped interpret results
      and strengthened arguments for e-learning and suggested future improvements for
      student use of e-learning. This mode of e-learning used to support face-to-face
      learning activities in the laboratory can be adapted for other disciplines and
      may assist students in developing a greater appreciation and a deeper approach
      for learning from their practical class experiences.

PMID- 18334572
TI  - Beyond the printed page: physiology education without a textbook?
AB  - Pedagogical innovations, ideas, and outcomes designed to enhance student learning
      in physiology courses are encouraged by our professional organizations and are
      actively discussed at conferences and in Advance in Physiological Education.
      Here, we report our experiment with freely available internet-based material as a
      substitute for the textbook for a single chapter on muscle physiology in a
      sophomore-level Human Physiology course. Student reactions to the textbookless
      curriculum were registered with the use of a questionnaire. Their responses
      indicated that they enjoyed the online material (animations, images, reviews,
      etc.), the emphasis on important concepts, and the variety of resources.
      Furthermore, students were almost unanimous in their praise for such pedagogical
      approaches to science education. Yet, students were reluctant to part with their
      textbooks. We believe that with subsequent iterations of this course we will be
      more successful at further separating the learning experience from the textbook.
      Reliance on freely available material may eventually relieve students from the
      burden of purchasing a costly textbook.

PMID- 18334573
TI  - IT-based activity in physiology education: an experience from a developing
      country.
AB  - Information technology (IT)-based components are included as active learning
      activities in medical curricula that have been shown to be more effective than
      most passive learning activities. In developing countries, these activities are
      not popular compared with developed countries. In this study, an IT-based
      assignment was carried out in physiology for undergraduates in Sri Lanka. We
      assessed certain basic IT capabilities before the assignment and found that the
      capability of using MS Word, e-mail, and the internet was limited to 68.3%,
      62.0%, and 49.2% of students, respectively, with 40.8% of students having some
      other IT capabilities. We found a considerable variation in IT capabilities among
      the students, which depended on IT learning at schools and the geographical
      locations where students came from. The main source of IT knowledge for students
      was an introductory IT course given in the medical school with the second source
      being private IT learning centers. Response to the IT-based assignment was very
      poor. The reasons for poor participation included a lack of time due to parallel
      subjects, poor IT knowledge, and poor IT resource availability. However, students
      were willing to have optional IT-based components and were aware that IT
      knowledge is important for medical students as well as doctors. This study shows
      the importance of improving IT knowledge in students and the need of improving IT
      resources in medical schools. With these improvements, physiology education can
      be enriched with more interactive IT-based learning activities, which help
      students to acquire knowledge more efficiently and effectively in developing
      countries like Sri Lanka.

PMID- 18334574
TI  - Hybrid lecture-online format increases student grades in an undergraduate
      exercise physiology course at a large urban university.
AB  - Hybrid courses allow students additional exposure to course content that is not
      possible in a traditional classroom environment. This exposure may lead to an
      improvement in academic performance. In this report, I describe the transition of
      a large undergraduate exercise physiology course from a traditional lecture
      format to a hybrid lecture-online format. A total of 658 final grades
      (traditional = 346, hybrid = 312) was used to evaluate the effect of course
      format on academic performance. The hybrid online portion was delivered using
      WebCT Vista, enhanced with various instructional technologies. The hybrid lecture
      portion was enhanced with an in-class response system. PowerPoint files were used
      to distribute in-class lectures in both formats of the course. Final student
      grades were 9.9% higher (83% of the increase due to an increase in the exam
      grade) when the course was administered in a hybrid format (P = 0.01), which
      translated to a one letter grade increase on a standard grading scale. Transition
      from a traditional lecture format to a hybrid format significantly enhanced
      student learning; presumably, this increase is due to the fact that students were
      able to increase their exposure to course content via access to material on
      WebCT.

PMID- 18334575
TI  - The journey of a sandwich: computer-based laboratory experiments about the human
      digestive system in high school biology teaching.
AB  - Teaching high school students about the digestive system can be a challenge for a
      teacher when s/he wants to overcome rote learning of facts without a deeper
      understanding of the physiological processes inside the alimentary tract. A
      series of model experiments illustrating the journey of a sandwich was introduced
      into teaching high school biology. Using a computer equipped with a commercially
      available data-acquisition system and a couple of sensors, it was possible to
      illustrate the basic underlying physical and chemical principles of digestion to
      the students. Students were able to investigate, through hands-on activities, the
      chewing force of the jaws, importance of the mechanical breakdown of food,
      enzymatic activity of pepsin and amylase, antibacterial activity of hydrochloric
      acid, and importance of the villi for absorption. Students found the experiments
      interesting and helpful for understanding the digestive process. Furthermore, the
      results from testing indicated that the students had a deeper understanding of
      the physiological processes.

PMID- 18334576
TI  - Teaching cardiac autonomic function dynamics employing the Valsalva (Valsalva
      Weber) maneuver.
AB  - In this report, a brief history of the Valsalva (Valsalva-Weber) maneuver is
      outlined, followed by an explanation on the use of this approach for the
      evaluation of cardiac autonomic function based on underlying heart rate changes.
      The most important methodological and interpretative aspects of the Valsalva
      Weber maneuver are critically updated, and some guidelines are established for
      simple application of the maneuver in a teaching or research laboratory setting.
      These include the hemodynamic and cardiac autonomic mechanisms involved,
      technical aspects such as the intensity and duration of the expiratory straining,
      frequency of maneuver sessions, training and posture of the individuals tested,
      different time- and grade change-dependent indexes of heart interval variation,
      and clinical application of the maneuver.

PMID- 18334577
TI  - The ultimate goal in neural regulation of cardiovascular function revisited.

PMID- 18334578
TI  - Identification of DIO2 as a new susceptibility locus for symptomatic
      osteoarthritis.
AB  - Osteoarthritis [MIM 165720] is a common late-onset articular joint disease for
      which no pharmaceutical intervention is available to attenuate the cartilage
      degeneration. To identify a new osteoarthritis susceptibility locus, a genome
      wide linkage scan and combined linkage association analysis were applied to 179
      affected siblings and four trios with generalized osteoarthritis (The GARP
      study). We tested, for confirmation by association, 1478 subjects who required
      joint replacement and 734 controls in a UK population. Additional replication was
      tested in 1582 population-based females from the Rotterdam study that contained
      94 cases with defined hip osteoarthritis and in 267 Japanese females with
      symptomatic hip osteoarthritis and 465 controls. Suggested evidence for linkage
      in the GARP study was observed on chromosome 14q32.11 (log of odds = 3.03, P =
      1.9 x 10(-4)). Genotyping tagging single-nucleotide polymorphisms covering three
      important candidate genes revealed a common coding variant (rs225014; Thr92Ala)
      in the iodothyronine-deiodinase enzyme type 2 (D2) gene (DIO2 [MIM 601413]) which
      significantly explained the linkage signal (P = 0.006). Confirmation and
      replication by association in the additional osteoarthritis studies indicated a
      common DIO2 haplotype, exclusively containing the minor allele of rs225014 and
      common allele of rs12885300, with a combined recessive odds ratio of 1.79, 95%
      confidence interval (CI) 1.37-2.34 with P = 2.02 x 10(-5) in female cases with
      advanced/symptomatic hip osteoarthritis. The gene product of this DIO2 converts
      intracellular pro-hormone-3,3',5,5'-tetraiodothyronine (T4) into the active
      thyroid hormone 3,3',5-triiodothyronine (T3) thereby regulating intracellular
      levels of active T3 in target tissues such as the growth plate. Our results
      indicate a new susceptibility gene (DIO2) conferring risk to osteoarthritis.

PMID- 18334579
TI  - Calpain 3 is a modulator of the dysferlin protein complex in skeletal muscle.
AB  - Muscular dystrophies comprise a genetically heterogeneous group of degenerative
      muscle disorders characterized by progressive muscle wasting and weakness. Two
      forms of limb-girdle muscular dystrophy, 2A and 2B, are caused by mutations in
      calpain 3 (CAPN3) and dysferlin (DYSF), respectively. While CAPN3 may be involved
      in sarcomere remodeling, DYSF is proposed to play a role in membrane repair. The
      coexistence of CAPN3 and AHNAK, a protein involved in subsarcolemmal
      cytoarchitecture and membrane repair, in the dysferlin protein complex and the
      presence of proteolytic cleavage fragments of AHNAK in skeletal muscle led us to
      investigate whether AHNAK can act as substrate for CAPN3. We here demonstrate
      that AHNAK is cleaved by CAPN3 and show that AHNAK is lost in cells expressing
      active CAPN3. Conversely, AHNAK accumulates when calpain 3 is defective in
      skeletal muscle of calpainopathy patients. Moreover, we demonstrate that AHNAK
      fragments cleaved by CAPN3 have lost their affinity for dysferlin. Thus, our
      findings suggest interconnectivity between both diseases by revealing a novel
      physiological role for CAPN3 in regulating the dysferlin protein complex.

PMID- 18334580
TI  - The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice
      Guideline.
AB  - OBJECTIVE: The objective of the study was to develop clinical practice guidelines
      for the diagnosis of Cushing's syndrome. PARTICIPANTS: The Task Force included a
      chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine
      Society, five additional experts, a methodologist, and a medical writer. The Task
      Force received no corporate funding or remuneration. CONSENSUS PROCESS: Consensus
      was guided by systematic reviews of evidence and discussions. The guidelines were
      reviewed and approved sequentially by The Endocrine Society's CGS and Clinical
      Affairs Core Committee, members responding to a web posting, and The Endocrine
      Society Council. At each stage the Task Force incorporated needed changes in
      response to written comments. CONCLUSIONS: After excluding exogenous
      glucocorticoid use, we recommend testing for Cushing's syndrome in patients with
      multiple and progressive features compatible with the syndrome, particularly
      those with a high discriminatory value, and patients with adrenal incidentaloma.
      We recommend initial use of one test with high diagnostic accuracy (urine
      cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone
      suppression test). We recommend that patients with an abnormal result see an
      endocrinologist and undergo a second test, either one of the above or, in some
      cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with
      concordant abnormal results should undergo testing for the cause of Cushing's
      syndrome. Patients with concordant normal results should not undergo further
      evaluation. We recommend additional testing in patients with discordant results,
      normal responses suspected of cyclic hypercortisolism, or initially normal
      responses who accumulate additional features over time.

PMID- 18334581
TI  - Evidence for insulin suppression of baseline luteinizing hormone in women with
      polycystic ovarian syndrome and normal women.
AB  - CONTEXT: In women with polycystic ovarian syndrome (PCOS), the relationship of
      insulin to LH secretion and responses to GnRH remains unresolved. A rigorous
      analytical examination of this relationship has not been performed. OBJECTIVE:
      Our objective was to determine the relationship of basal LH secretion and
      responses to GnRH, insulin, and other endocrine variables in normal and PCOS
      women. DESIGN: In PCOS and normal women, mean composite 12-h LH secretion was
      analyzed for correlating factors. LH responses to varying doses of GnRH during a
      fixed rate of insulin infusion and LH responses to a fixed dose of GnRH during
      varying doses of insulin infusion were analyzed for contributing factors.
      PATIENTS AND SETTING: Eighteen PCOS and 21 normal women underwent studies of
      frequent blood sampling and GnRH stimulation before and during insulin infusion
      at the General Clinical Research Center, University of California, San Diego.
      MAIN OUTCOME MEASURES: Group mean composite 12-h LH levels were assessed with
      respect to other endocrine variables. In addition, LH responses to GnRH with or
      without insulin infusion were assessed. RESULTS: In normal women, insulin
      negatively predicted mean LH. In PCOS, the combined effect of body mass index
      (negative) and testosterone (positive) predicted LH. The best predictor of LH was
      body mass index and insulin combined. Basal LH and LH responses to GnRH were
      unaltered by insulin infusion in normal women. These measures were reduced during
      insulin infusion in PCOS women. CONCLUSIONS: In PCOS, insulin infusion suppresses
      pituitary response to GnRH. In normal women, insulin negatively correlates with
      mean LH and suppresses GnRH response at a high infusion rate.

PMID- 18334582
TI  - Gender of pediatric recombinant human growth hormone recipients in the United
      States and globally.
AB  - BACKGROUND: Gender disparities were found in reports of early pediatric
      recombinant human GH (rhGH) use in the United States. With rhGH entering its
      third decade, we sought to examine U.S. gender-based treatment patterns and how
      these patterns compare with that of other countries. METHODS: All children
      entered in the Pfizer International Growth Study, a database designed to document
      long-term outcomes and safety of Genotropin (Pfizer, New York, NY), were
      categorized by gender, location, date and age of therapy initiation, and
      diagnosis. Measures of national health status, health care expenditure, general
      economic indices, and mean adult heights were also compared. RESULTS: Throughout
      the past 20 yr, the United States had an almost 2:1 male to female ratio overall.
      The gender ratio depended on the specific indication and age. There was no
      consistent relation to geographical region, pediatric population size, or density
      of pediatric endocrinologists. Male predominance was seen in Asia (mostly Japan),
      the United States, and Europe/Australia/New Zealand (65, 64, and 55%,
      respectively), but not the rest of the world (47%), where rhGH was prescribed
      less frequently. In the countries with the greatest rhGH use, the gender ratios
      depended on the specific indications but did not correlate with mean adult
      height, national health care measures, or general economic indices. CONCLUSIONS:
      Male predominance among U.S. pediatric rhGH recipients persists, especially for
      indications without a clear organic etiology. Global differences in gender ratios
      suggest that factors other than biology are at play. We speculate that social and
      cultural pressures and the health care systems' permissiveness toward paying for
      rhGH therapy contribute to these international differences.

PMID- 18334583
TI  - Adipokine protein expression pattern in growth hormone deficiency predisposes to
      the increased fat cell size and the whole body metabolic derangements.
AB  - CONTEXT: GH deficiency (GHD) in adults is associated with central adiposity,
      dyslipidemia, and insulin resistance. OBJECTIVE: The objective of the study was
      to test the hypothesis that GHD might change the spectrum of adipokines and thus
      influence the adipose tissue and the whole-body metabolic and inflammatory status
      leading to development of insulin resistance. DESIGN: This was a single-center
      observational study with a cross-sectional design. PARTICIPANTS AND METHODS:
      Protein arrays were used to characterize adipokines expressed in the sc adipose
      tissue obtained from young GHD adults and compared with age-, gender-, and body
      mass index (BMI)-matched group of healthy individuals. All subjects underwent an
      oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and magnetic
      resonance imaging examination. RESULTS: Presence of abdominal obesity, enlarged
      adipocytes, increased circulating high-sensitivity C-reactive protein, impaired
      glucose tolerance, and decreased insulin action were found in GHD. Changes in
      adipokine protein expression due to GHD were highly dependent on the obesity
      phenotype. Lean GHD individuals (BMI approximately 23 kg/m(2)) had decreased
      protein levels for stem cell factor and epithelial growth factor, indicating a
      possible defect in adipocyte differentiation and proliferation. Decrease of
      vascular endothelial growth factor, stromal cell-derived factor, angiopoietin-2,
      and brain-derived neurotrophic factor advocated for attenuated angiogenesis and
      neurogenesis. Presence of obesity (BMI approximately 31 kg/m(2)) eliminated these
      inhibitory effects. However, adipose tissue expansion in GHD individuals was
      paralleled by an elevation of adipose tissue proinflammatory cytokines (IL-1beta,
      interferon-gamma) and chemoattractants (interferon-inducible T cell alpha
      chemoattractant, monocyte chemotactic protein-2, monocyte chemotactic protein-3,
      eotaxin). CONCLUSION: Our data demonstrate that GHD modulates adipokine and
      cytokine protein expression pattern, which might influence the adipose tissue
      growth and differentiation and predispose to tissue hypoxia, inflammation, and a
      defect in the whole-body insulin action.

PMID- 18334584
TI  - Beneficial effects of propylthiouracil plus L-thyroxine treatment in a patient
      with a mutation in MCT8.
AB  - CONTEXT: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a
      distinct X-linked phenotype of severe psychomotor retardation and consistently
      elevated T(3) levels. Lack of MCT8 transport of T(3) in neurons could explain the
      neurological phenotype. OBJECTIVE: Our objective was to determine whether the
      high T(3) levels could also contribute to some critical features observed in
      these patients. RESULTS: A 16-yr-old boy with severe psychomotor retardation and
      hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed
      puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter),
      and elevated serum free T(3) (FT(3)) level (11.3 pmol/liter), without FT(4) and
      TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral
      overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU)
      and then PTU plus levothyroxine (LT(4)) was tested. After PTU (200 mg/d), serum
      FT(4) was undetectable, FT(3) was reduced (3.1 pmol/liter) with high TSH levels
      (50.1 mU/liter). Serum SHBG levels were reduced (72 nmol/liter). While PTU
      prescription was continued, high LT(4) doses (100 microg/d) were needed to
      normalize serum TSH levels (3.18 mU/liter). At that time, serum FT(4) was normal
      (16.4 pmol/liter), and FT(3) was slightly high (6.6 pmol/liter). Tachycardia was
      abated (84 beats/min), weight gain was 3 kg in 1 yr, and SHBG was 102 nmol/liter.
      CONCLUSIONS: 1) When thyroid hormone production was reduced by PTU, high doses of
      LT(4) (3.7 microg/kg.d) were needed to normalize serum TSH, confirming that
      mutation of MCT8 is a cause of resistance to thyroid hormone. 2) High T(3) levels
      might exhibit some deleterious effects on adipose, hepatic, and cardiac levels.
      3) PTU plus LT(4) could be an effective therapy to reduce general adverse
      features, unfortunately without benefit on the psychomotor retardation.

PMID- 18334585
TI  - Effect of low-dose oral contraceptives on metabolic risk factors in African
      American women.
AB  - CONTEXT: The effect of oral contraceptive pill (OCP) use on cardiovascular risk
      in African-American women is unknown. OBJECTIVE: Our objective was to examine in
      African-American women the effect of OCP use on insulin resistance, glucose
      intolerance, and triglycerides (TGs). DESIGN: This was a cross-sectional study.
      SETTING: The study was conducted at the National Institutes of Health Clinical
      Research Center. PARTICIPANTS: A total of 104 healthy nondiabetic African
      American women [21 OCP users, 83 controls, age mean +/- sd, 34.7 +/- 7.6 yr, body
      mass index (BMI) 31 +/- 8.4 kg/m(2)] was included in the study. INTERVENTIONS:
      Subjects had oral glucose tolerance tests, insulin-modified frequently sampled iv
      glucose tolerance tests, and fasting lipid profiles. Insulin resistance was
      determined by the insulin sensitivity index (S(I)). MAIN OUTCOME MEASURES:
      Insulin resistance, glucose tolerance status, and TG levels were determined.
      RESULTS: Fasting glucose did not differ between OCP users and controls (P =
      0.27). In contrast, compared with controls, 2-h glucose (135 +/- 23 vs.120 +/- 25
      mg/dl; P = 0.01) and fasting TGs (73 +/- 31 vs.57 +/- 27 mg/dl; P = 0.02) were
      higher in OCP users. OCP users tended to be more insulin resistant than controls
      (S(I): 2.51 +/- 2.01 vs. 3.46 +/- 2.09; P = 0.09). Multiple regression analysis
      revealed that BMI, age, and OCP use were significant determinants of 2-h glucose
      (adjusted R(2) = 0.37; P < 0.001) and TG levels (adjusted R(2) = 0.21; P <
      0.001). As BMI was a determinant of both 2-h glucose and TGs, participants were
      divided into nonobese and obese groups, and the analyses repeated. Among the
      nonobese women, the OCP users were more insulin resistant (S(I): 2.91 +/- 1.58
      vs. 4.35 +/- 1.88; P = 0.03) and had a higher prevalence of glucose intolerance
      than controls (odds ratio 5.7; 95% confidence interval 1.4-24; P = 0.01).
      CONCLUSION: In African-American women, OCP use is associated with an increase in
      markers of cardiovascular risk manifested by increased insulin resistance,
      glucose intolerance, and elevated TGs.

PMID- 18334586
TI  - Treatment of advanced adrenocortical carcinoma with erlotinib plus gemcitabine.
AB  - CONTEXT: Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis.
      In advanced disease, mitotane given as monotherapy or combined either with
      etoposide, doxorubicin, and cisplatin or with streptozotocin is the recommended
      first-line therapy. However, many patients have progressive disease despite
      treatment with these regimens. OBJECTIVE: Our objective was to evaluate the
      efficacy of the epidermal growth factor receptor inhibitor erlotinib plus
      gemcitabine as salvage therapy in ACC patients with very advanced ACC.
      DESIGN/SETTING: The study consisted of case series collected from different
      centers (primary care and referral centers) in Germany in 2006-2007. PATIENTS AND
      INTERVENTION: Patients registered with the German ACC Registry with progressive
      ACC after two to four previous systemic therapies were offered treatment with
      erlotinib and gemcitabine. Oral erlotinib (100 mg/d) was administered on a daily
      basis and gemcitabine (800 mg/m(2)) iv every 14 d. MAIN OUTCOME MEASURE: We
      evaluated tumor response according to response evaluation criteria in solid
      tumors (RECIST) criteria after 12 wk of treatment. RESULTS: Ten patients have
      been treated with erlotinib and gemcitabine. Only one in 10 patients experienced
      a minor response (progression-free survival 8 months), whereas eight patients had
      progressive disease at the first staging. One patient had to stop therapy after
      the first administration of gemcitabine due to cerebral seizure. Nine of 10
      patients had died after a median of 5.5 months after treatment initiation. In
      addition to the seizure, one patient experienced severe pneumonia (grade III),
      and in one, gemcitabine administration had been delayed due to prolonged
      neutropenia. All other adverse events were mild (grade I-II). CONCLUSIONS:
      Salvage chemotherapy using erlotinib plus gemcitabine has very limited to no
      activity in patients with very advanced ACC.

PMID- 18334587
TI  - Plasma osteopontin increases after bariatric surgery and correlates with markers
      of bone turnover but not with insulin resistance.
AB  - CONTEXT: Osteopontin (OPN) is a multifunctional protein involved in bone
      metabolism, cardiovascular disease, diabetes, and obesity. OPN levels are
      elevated in the plasma and adipose tissue of obese subjects, and are decreased
      with diet-induced weight loss. OBJECTIVE: We investigated the effect of bariatric
      surgery on plasma OPN concentrations in morbidly obese patients. SETTING: The
      study was performed at a university hospital. SUBJECTS: We investigated 40 obese
      patients aged 43.1 +/- 1.8 yr, scheduled to undergo bariatric surgery. Roux-en-Y
      gastric bypass (RYGB) was performed in 30 subjects (27 females, three males), and
      laparoscopic adjustable gastric banding (LAGB) in 10 subjects (eight females, two
      males). STUDY DESIGN: All patients were studied before and 1 yr (10.3-14.8
      months) after the intervention. MAIN OUTCOME MEASURES: OPN, leptin, C-reactive
      protein, insulin, the homeostatic model assessment insulin resistance index,
      calcium, 25-hydroxyvitamin D, C telopeptide, and osteocalcin were determined.
      RESULTS: Both bariatric procedures significantly reduced body weight, body mass
      index, insulin, leptin, and C-reactive protein 1 yr after surgery. Plasma OPN
      increased from 31.4 +/- 3.8 to 52.8 +/- 3.7 ng/ml after RYGB (P < 0.001) and from
      29.8 +/- 6.9 to 46.4 +/- 10.6 ng/ml after LAGB (P = 0.042). Preoperative OPN
      correlated with age, insulin, the homeostatic model assessment insulin resistance
      index, and postoperative OPN. Postoperative OPN correlated with C telopeptide and
      osteocalcin. CONCLUSIONS: One year after RYGB and LAGB, plasma OPN levels
      significantly increased and correlated with biomarkers of bone turnover. Unlike
      other proinflammatory cytokines, OPN does not normalize but increases further
      after bariatric surgery.

PMID- 18334588
TI  - Associations of serum sex hormone-binding globulin and sex hormone concentrations
      with hip fracture risk in postmenopausal women.
AB  - CONTEXT: Endogenous estradiol, testosterone, and SHBG may influence the risk of
      hip fracture. DESIGN AND METHODS: From the Women's Health Initiative
      Observational Study, 39,793 eligible postmenopausal women did not have a previous
      hip fracture and were not using estrogen or other bone-active therapies. Of
      these, 400 who had a first-time nonpathological hip fracture (median follow-up, 7
      yr) were matched to 400 controls by age, ethnicity, and baseline blood draw date.
      Estradiol, testosterone, and SHBG were measured in banked baseline serum.
      RESULTS: Compared with women in the lowest tertiles, those with bioavailable
      testosterone in the highest tertile had a lower risk [odds ratio (OR) = 0.62; 95%
      confidence interval (CI) = 0.44-0.88]; those with bioavailable estradiol in the
      highest tertile had a lower risk (OR = 0.44; 95% CI = 0.29-0.66), and those with
      SHBG in the highest tertile had a higher risk (OR = 1.90; 95% CI = 1.31-2.74) of
      hip fracture. In models with all three hormones and potential confounders, high
      SHBG remained a strong independent risk factor (OR = 1.76; 95% CI = 1.12-2.78),
      high bioavailable testosterone remained protective (OR = 0.64; 95% CI = 0.40
      1.00), but estradiol no longer was associated (OR = 0.72; 95% CI = 0.42-1.23).
      CONCLUSIONS: High serum SHBG is associated with an increased risk of subsequent
      hip fracture and high endogenous testosterone with a decreased risk, independent
      of each other, serum estradiol concentration, and other putative risk factors.
      But endogenous estradiol has no independent association with hip fracture.

PMID- 18334589
TI  - Evidence for acyl-ghrelin modulation of growth hormone release in the fed state.
AB  - CONTEXT: The timing and frequency of GH secretory episodes is regulated by GHRH
      and somatostatin. This study provides evidence for amplification of these GH
      pulses by endogenous acyl-ghrelin. DESIGN: Blood was sampled every 10 min for
      26.5 h during a fed admission with standardized meals and also during the final
      24 h of a 61.5-h fast. GH secretion profiles were derived from deconvolution of
      10-min sampling data, and full-length acyl-ghrelin levels were measured using a
      newly developed two-site sandwich assay. SETTING: The study was conducted at a
      university hospital general clinical research center. PARTICIPANTS: Participants
      included eight men with mean (+/- sd) age 24.5 +/- 3.7 yr (body mass index 24 +/-
      2.1 kg/m(2)). RESULTS: Correlations were computed between amplitudes of
      individual GH secretory events and the average acyl-ghrelin concentration in the
      60-min interval preceding each GH burst. In the fed state, the peak correlations
      were positive for all subjects and significantly higher than in the fasting state
      when acyl-ghrelin levels declined [mean (+/- sem): 0.7 (0.04) vs. 0.29 (0.08), P
      = 0.017]. In addition, long-term fasting was associated with an increase in the
      GH secretory pulse mass and amplitude but not frequency [fed vs. fasting pulse
      mass: 0.22 (0.05) vs. 0.44 (0.06) microg/liter, P = 0.002; amplitude: 5.2 (1.3)
      vs. 11.8 (1.9) microg/liter/min, P = 0.034; pulses per 24 h: 19.4 (0.5) vs. 22.0
      (1.4), P = 0.1]. CONCLUSION: Our data support the hypothesis that under normal
      conditions in subjects given regular meals endogenous acyl-ghrelin acts to
      increase the amplitude of GH pulses.

PMID- 18334590
TI  - Changes over 14 years in androgenicity and body mass index in a biracial cohort
      of reproductive-age women.
AB  - BACKGROUND: Body mass index (BMI) is directly related to testosterone (total T
      and free T) and inversely to SHBG cross-sectionally, but little is known about
      how changes in body fat and androgen markers affect each other over time.
      METHODS: Participants included 969 White and Black women from the Coronary Artery
      Risk Development in Young Adults (CARDIA) cohort, who were ages 18-30 at entry
      into the study and were pre- or perimenopausal 16 yr later at the time of the
      CARDIA Women's Study (CWS). Total T and SHBG were assayed from specimens drawn at
      the CWS examination and stored serum from the yr 2 and 10 CARDIA exams. Free T
      was calculated based on total T and SHBG. BMI and waist circumference were
      measured at yr 2, 10, and 16. RESULTS: Despite clinically significant increases
      in BMI and waist circumference, total T and free T tended to decline, whereas
      SHBG remained relatively constant. BMI and waist circumference were directly
      correlated with free T and inversely correlated with SHBG in cross-sectional
      analyses. In longitudinal, multivariable analyses, an annualized increase in BMI
      was inversely related to a concurrent annualized decrease in SHBG (beta = -0.79
      ng/dl, and se = 0.22 in Blacks; beta = -1.07 ng/dl; and se = 0.31 in Whites).
      However, early increases in BMI were not related to later decreases in SHBG.
      CONCLUSION: Increases in adiposity are closely tied to decreases in SHBG, but
      changes in BMI and SHBG may occur concurrently rather than sequentially.

PMID- 18334591
TI  - Relationship of serum antimullerian hormone concentration to age at menopause.
AB  - BACKGROUND: Serum antimullerian hormone (AMH) levels are highly correlated with
      antral follicle counts, while being menstrual cycle independent and easily
      measurable. However, AMH, unlike antral follicle counts, has not been tested as
      yet as a predictor of reproductive status. By relating AMH levels to the age
      distribution of reproductive events like onset of menopause, we tested this
      hypothesis. METHODS: AMH levels were measured in 144 fertile normal volunteers
      and used to determine an estimate of mean AMH as a function of age. Data on the
      onset of menopause were obtained from the population-based Prospect-European
      Prospective Investigation into Cancer and Nutrition [Prospect-EPIC] cohort.
      Estimation of an AMH threshold to predict menopause was done by maximum
      likelihood using the observed (Prospect-EPIC) distribution of age at menopause
      and the predictive distribution from this AMH threshold. Predictions of age at
      menopause follow from an individual woman's AMH relative to percentiles of the
      distribution of AMH for a given age, and the corresponding percentiles of the
      predictive distribution of age at menopause. RESULTS: There was good conformity
      between the observed distribution of age at menopause and that predicted from
      declining AMH levels. CONCLUSIONS: The similarity between observed and predictive
      distributions of age at menopause supports the hypothesis that AMH levels are
      related to onset of menopause. Results of this study suggest that AMH is able to
      specify a woman's reproductive age more realistically than chronological age
      alone.

PMID- 18334592
TI  - Insulin-sensitizing effects of exercise on adiponectin and retinol-binding
      protein-4 concentrations in young and middle-aged women.
AB  - CONTEXT: Exercise training enhances insulin sensitivity. Changes in retinol
      binding protein-4 (RBP4) and adiponectin levels are linked to insulin resistance.
      OBJECTIVE: We tested whether the insulin-sensitizing effect of exercise is
      associated with age-related changes in circulating RBP4 and adiponectin levels in
      women. DESIGN, SUBJECTS, AND INTERVENTION: We studied 36 healthy young (22.4 +/-
      2.8 yr) and 38 middle-aged (59.8 +/- 5.9 yr) women. All subjects performed 60 min
      of aerobic exercise three times per week for 10 wk at about 70% maximal exercise
      capacity. RESULTS: After a 10-wk training program, maximal exercise capacity was
      significantly increased in both young and middle-aged women, suggesting increased
      oxidative capacity. Insulin sensitivity was also improved, as indicated by
      decreases in plasma insulin levels and homeostasis model assessment for insulin
      resistance index. Serum adiponectin and RBP4 concentrations were increased and
      decreased more in older than younger women, respectively (P < 0.01).
      Concurrently, circulating transthyretin levels were also decreased in older
      subjects in response to exercise training. The older women showed higher
      correlations between changes in adiponectin or RBP4 levels and obesity indices or
      metabolic parameters than the younger group. When subjects showing increasing
      adiponectin or decreasing RBP4 levels were classified as responders, there were
      higher correlations between these changes in responders than in nonresponders.
      CONCLUSIONS: We conclude that the mechanism for the insulin-sensitizing effects
      of exercise could involve increased adiponectin and reduced RBP4 levels in
      exercise-trained women. These data suggest that alterations in circulating RBP4
      and adiponectin levels could play an important role in regulating insulin
      sensitivity.

PMID- 18334593
TI  - Doping test results dependent on genotype of uridine diphospho-glucuronosyl
      transferase 2B17, the major enzyme for testosterone glucuronidation.
AB  - CONTEXT: Testosterone abuse is conventionally assessed by the urinary
      testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered
      suspicious. The large variation in testosterone glucuronide (TG) excretion and
      its strong association with a deletion polymorphism in the uridine diphospho
      glucuronosyl transferase (UGT) 2B17 gene challenge the accuracy of the T/E ratio
      test. OBJECTIVE: Our objective was to investigate whether genotype-based cutoff
      values will improve the sensitivity and specificity of the test. DESIGN: This was
      an open three-armed comparative study. PARTICIPANTS: A total of 55 healthy male
      volunteers with either two, one, or no allele [insertion/insertion,
      insertion/deletion, or deletion/deletion (del/del)] of the UGT2B17 gene was
      included in the study. INTERVENTION: A single im dose of 500 mg testosterone
      enanthate was administered. MAIN OUTCOME MEASURES: Urinary excretion of TG after
      dose and the T/E ratio during 15 d were calculated. RESULTS: The degree and rate
      of increase in the TG excretion rate were highly dependent on the UGT2B17
      genotype with a 20-fold higher average maximum increase in the
      insertion/insertion group compared with the del/del group. Of the del/del
      subjects, 40% never reached the T/E ratio of 4.0 on any of the 15 d after the
      dose. When differentiated cutoff levels for the del/del (1.0) and the other
      genotypes (6.0) were applied, the sensitivity increased substantially for the
      del/del group, and false positives in the other genotypes were eliminated.
      CONCLUSIONS: Consideration of the genetic variation in disposition of androgens
      will improve the sensitivity and specificity of the testosterone doping test.
      This is of interest not only for combating androgen doping in sports, but also
      for detecting and preventing androgen abuse in society.

PMID- 18334594
TI  - Accuracy of diagnostic tests for Cushing's syndrome: a systematic review and
      metaanalyses.
AB  - CONTEXT: The diagnosis of Cushing's syndrome (CS) requires the use of tests of
      unregulated hypercortisolism that have unclear accuracy. OBJECTIVE: Our objective
      was to summarize evidence on the accuracy of common tests for diagnosing CS. DATA
      SOURCES: We searched electronic databases (MEDLINE, EMBASE, Web of Science,
      Scopus, and citation search for key articles) from 1975 through September 2007
      and sought additional references from experts. STUDY SELECTION: Eligible studies
      reported on the accuracy of urinary free cortisol (UFC), dexamethasone
      suppression test (DST), and midnight cortisol assays vs. reference standard in
      patients suspected of CS. DATA EXTRACTION: Reviewers working in duplicate and
      independently extracted study characteristics and quality and data to estimate
      the likelihood ratio (LR) and the 95% confidence interval (CI) for each result.
      DATA SYNTHESIS: We found 27 eligible studies, with a high prevalence [794 (9.2%)
      of 8631 patients had CS] and severity of CS. The tests had similar accuracy: UFC
      (n = 14 studies; LR+ 10.6, CI 5.5-20.5; LR- 0.16, CI 0.08-0.33), salivary
      midnight cortisol (n = 4; LR+ 8.8, CI 3.5-21.8; LR- 0.07, CI 0-1.2), and the 1-mg
      overnight DST (n = 14; LR+ 16.4, CI 9.3-28.8; LR- 0.06, CI 0.03-0.14). Combined
      testing strategies (e.g. a positive result in both UFC and 1-mg overnight DST)
      had similar diagnostic accuracy (n = 3; LR+ 15.4, CI 0.7-358; LR- 0.11, CI 0.007
      1.57). CONCLUSIONS: Commonly used tests to diagnose CS appear highly accurate in
      referral practices with samples enriched with patients with CS. Their performance
      in usual clinical practice remains unclear.

PMID- 18334595
TI  - Visceral adiposity without overweight in children born small for gestational age.
AB  - CONTEXT: Children born small for gestational age (SGA) tend to develop catch-up
      growth in infancy and become overweight by the age of 6 yr. Weight control is
      advocated as a preventive measure, but it is unknown whether such control
      suffices to prevent visceral fat excess and hypoadiponectinemia. SETTING: The
      study was performed at a university hospital. STUDY POPULATION AND DESIGN: A
      total of 64 children (32 matched pairs) aged 6 yr, of whom 32 were born
      appropriate for gestational age and 32 were born SGA, and had subsequently
      developed spontaneous catch-up growth were included in the study; matching was
      performed for gender, height, weight, and, thus, body mass index. MAIN OUTCOMES:
      Fasting insulin, IGF-I, high molecular weight adiponectin, leptin, visfatin, and
      lean and fat mass were calculated by absorptiometry, and abdominally sc and
      visceral fat by magnetic resonance imaging. RESULTS: After strict matching, SGA
      children had a total lean mass, total fat mass, leptinemia, and visfatinemia
      comparable to those in the appropriate for gestational age children, but they
      still had higher fasting insulin and IGF-I levels (P < 0.01), much lower high
      molecular weight adiponectin levels (P < 0.0001), and a striking shift from
      abdominally sc to visceral fat (P < 0.0001). Fasting insulin (r = 0.52; P <
      0.00001) was a major determinant of visceral fat in boys and girls, explaining
      28% of its variance. CONCLUSIONS: SGA children tend to be viscerally adipose and
      hypo-adiponectinemic, even if they are not overweight. Therefore, measures beyond
      weight control seem to be needed to allow most SGA children to normalize their
      body composition and endocrine-metabolic homeostasis.

PMID- 18334596
TI  - Enhancement of vascular endothelial function by recombinant human thyrotropin.
AB  - CONTEXT: The cardiovascular consequences of thyroid diseases are attributed to
      the altered secretion of thyroid hormones. The possibility that TSH also affects
      the cardiovascular system has been poorly explored. Endothelial cells and
      vascular smooth muscle cells possess TSH receptors. OBJECTIVE: The study was
      designed to determine whether TSH exerts any effect on vascular homeostasis.
      SUBJECTS AND METHODS: Two different double-blind, controlled studies were
      performed, one in eight healthy volunteers and the other in six thyroidectomized
      patients. Recombinant human (rh) TSH (or saline) was infused intrabrachially (1
      mU/min) to raise TSH to severe hypothyroidism levels (approximately 100
      microU/ml). Endothelium-dependent and -independent vasodilation was tested by
      intraarterial infusion of acetylcholine and sodium nitroprusside, respectively,
      and forearm blood flow was measured by plethysmography. RESULTS: Endothelium
      dependent vasodilation was potentiated by rhTSH (P < 0.05 for the treatment
      effect; general linear model). The dynamics of the response was also profoundly
      affected by rhTSH because the dose-response curve was much steeper than in
      controls (P < 0.02 for the interaction between TSH and acetylcholine). rhTSH had
      no effect on endothelium-independent vasodilation (P = NS for both treatment and
      interaction). During rhTSH infusion, free T(3) levels increased slowly from 2.3
      +/- 0.2 to 3.6 +/- 0.2 pg/ml. In thyroidectomized patients, rhTSH potentiated
      endothelium-mediated vasodilation to an extent similar to that of healthy
      subjects (P = 0.05 for the treatment effect and P = 0.01 for the interaction),
      without affecting the response to nitroprusside. In these patients, thyroid
      hormones remained unchanged during rhTSH infusion. CONCLUSIONS: rhTSH exerts
      marked effects on the resistance vessels by enhancing endothelial-mediated
      vasodilation, independent of changes in thyroid hormone concentration.

PMID- 18334597
TI  - Potent, selective and cell penetrant inhibitors of SF-1 by functional ultra-high
      throughput screening.
AB  - The steroidogenic factor 1 (SF-1, also known as NR5A1) is a transcription factor
      belonging to the nuclear receptor superfamily. Whereas most of the members of
      this family have been extensively characterized, the therapeutic potential and
      pharmacology of SF-1 still remains elusive. Described here is the identification
      and characterization of selective inhibitory chemical probes of SF-1 by a
      rational ultra-high-throughput screening (uHTS) strategy. A set of 64,908
      compounds from the National Institute of Health's Molecular Libraries Small
      Molecule Repository was screened in a transactivation cell-based assay employing
      a chimeric SF-1 construct. Two analogous isoquinolinones, ethyl 2-[2-[2-(2,3
      dihydro-1,4-benzodioxin-7-ylamino)-2-oxoethyl]-1-oxoisoquinolin-5
      yl]oxypropanoate (SID7969543) and ethyl 2-[2-[2-(1,3-benzodioxol-5-ylmethylamino)
      2-oxoethyl]-1-oxoisoquinolin-5-yl]oxypropanoate and (SID7970631), were identified
      as potent submicromolar inhibitors, yielding IC(50) values of 760 and 260 nM. The
      compounds retained their potency in a more physiologic functional assay employing
      the full-length SF-1 protein and its native response element, yielding IC(50)
      values of 30 and 16 nM, respectively. The selectivity of these isoquinolinones
      was confirmed via transactivation-based functional assays for RAR-related orphan
      receptor A (RORA), Herpes simplex virus transcriptional activator protein Vmw65
      (VP16), and liver receptor homolog 1 (LRH-1). Their cytotoxicity, solubility,
      permeability and metabolic stability were also measured. These isoquinolinones
      represent valuable chemical probes to investigate the therapeutic potential of SF
      1.

PMID- 18334598
TI  - The nuclear factor-kappa B pathway regulates cytochrome P450 3A4 protein
      stability.
AB  - We have previously observed that CYP3A4 protein levels are suppressed by
      inhibition of the proteasome in primary cultured hepatocytes. Because this result
      is opposite of what would be expected if CYP3A4 were degraded by the proteasome,
      it seemed likely that there might be another protein susceptible to proteasomal
      degradation that regulated CYP3A4 expression. In this study, we evaluated whether
      the nuclear factor-kappaB (NF-kappaB) pathway was involved in that process. Our
      model system used an adenovirus system to express CYP3A4 protein in HepG2 cells,
      which are derived from human cancer cells. Similar to results in primary
      hepatocytes, the inhibition of the proteasome with N-benzoyloxycarbonyl (Z)-Leu
      Leu-leucinal (MG132) suppresses CYP3A4 protein levels. We also found that MG132
      treatment had a broad affect on the NF-kappaB pathway, including down-regulation
      of NF-kappaB DNA binding activity and IkappaB kinase (IKK)alpha levels and up
      regulation of IKKbeta and inhibitory kappaB levels. Treatment of the HepG2 cells
      with several structurally distinct NF-kappaB inhibitors also suppressed CYP3A4
      protein levels. When the HepG2 cells were treated with cycloheximide, a general
      inhibitor of protein synthesis, the loss of CYP3A4 protein was accelerated by
      cotreatment with either proteasome or NF-kappaB inhibitors. These results
      indicate that NF-kappaB activity regulated CYP3A4 protein stability, and they
      suggest that the NF-kappaB pathway was responsible for the decrease in CYP3A4
      protein levels that resulted from the proteasomal inhibition.

PMID- 18334599
TI  - Primary peripheral T cells become susceptible to 2,3,7,8-tetrachlorodibenzo-p
      dioxin-mediated apoptosis in vitro upon activation and in the presence of
      dendritic cells.
AB  - Although the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on T
      cells in vivo have been well characterized, attempts to reproduce these findings
      in vitro have not been successful. In the current study, we examined whether
      activation or the presence of dendritic cells (DCs) would make primary naive T
      cells from C57BL/6 mice susceptible to TCDD-induced apoptosis in vitro. Although
      nonactivated primary T cells cultured with 10 to 1000 nM TCDD were relatively
      resistant to apoptosis, they became sensitive to apoptosis upon activation with
      concanavalin A (ConA). Moreover, ConA-activated T cells cultured in the presence
      of DCs showed highest levels of TCDD-induced apoptosis. Likewise, primary T cells
      from OT.II.2a mice cultured with specific ovalbumin peptide and syngeneic DCs
      showed higher levels of apoptosis compared with similar nonactivated T cells. T
      cell activation led to up-regulation of aryl hydrocarbon receptor (AhR), Fas, and
      Fas-ligand (FasL) expression. In addition, DC maturation and culture with TCDD
      caused significant induction of FasL. TCDD-mediated apoptosis in activated
      peripheral T cells was AhR-dependent. Analysis of why nonactivated T cells are
      more resistant, whereas activated T cells are sensitive to TCDD-induced apoptosis
      revealed that TCDD treatment of activated but not nonactivated T cells led to
      down-regulation of cellular FLICE inhibitory protein (c-FLIP), an inhibitor of
      apoptosis. Moreover, down-regulation of c-FLIP using small interfering RNA in
      nonactivated T cells made them sensitive to TCDD-induced apoptosis. The current
      study demonstrates for the first time that TCDD can induce apoptosis in vitro in
      peripheral T cells upon activation and in the presence of DCs and that this may
      be mediated by down-regulation of c-FLIP.

PMID- 18334600
TI  - Covalent binding of the nitroso metabolite of sulfamethoxazole is important in
      induction of drug-specific T-cell responses in vivo.
AB  - Immune-mediated drug hypersensitivity reactions (IDHRs) represent a significant
      problem due to their unpredictable and severe nature, as well as the lack of
      understanding of the pathogenesis. Sulfamethoxazole (SMX), a widely used
      antibiotic, has been used as a model compound to investigate the underlying
      mechanism of IDHRs because it has been associated with a relatively high
      incidence of hypersensitivity. Previous studies by others showed that
      administration of 4-(nitroso)-N-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide (SMX
      NO), the reactive metabolite of SMX, to rats resulted in the generation of SMX
      specific antibodies and ex vivo splenocyte proliferative responses, as well as
      haptenation of skin keratinocytes, circulating peripheral blood mononuclear
      cells, and splenocytes. The objective of the present study was to further
      investigate SMX-NO-protein binding in relationship to its immunogenicity. In
      female DBA/1 mice treated with SMX-NO, varying degrees of SMX-NO-dependent T-cell
      responses and SMX-NO-protein adduct formation were observed in the spleen and in
      inguinal, brachial, and axillary lymph nodes. The data suggested a tissue
      specific threshold of SMX-NO dosage that triggers the detection of adducts and
      immune response. Furthermore, serum albumin and immunoglobulin were identified as
      protein targets for SMX-NO modification. It seemed that these adducts were formed
      in the blood, circulated to lymphoid tissues, and initiated SMX-NO-dependent
      immune responses. Collectively, these data revealed a causal link between the
      deposition of SMX-NO-protein adducts in a lymphoid tissue and the induction of
      immune response in that tissue. Our findings also suggest that the immunogenicity
      of SMX-NO is determined by the immunogenic nature of the hapten, rather than
      special characteristics of the adducted protein.

PMID- 18334601
TI  - Kavalactones protect neural cells against amyloid beta peptide-induced
      neurotoxicity via extracellular signal-regulated kinase 1/2-dependent nuclear
      factor erythroid 2-related factor 2 activation.
AB  - One hallmark of Alzheimer's disease is the accumulation of amyloid beta-peptide
      (AP), which can initiate a cascade of oxidative events that may result in
      neuronal death. Because nuclear factor erythroid 2-related factor 2 (Nrf2) is the
      major regulator for a battery of genes encoding detoxifying and antioxidative
      enzymes via binding to the antioxidant response element (ARE), it is of great
      interest to find nontoxic activators of Nrf2 rendering neuronal cells more
      resistant to AP toxicity. Using ARE-luciferase assay and Western blot, we provide
      evidence that the kavalactones methysticin, kavain, and yangonin activate Nrf2
      time- and dose-dependently in neural PC-12 and astroglial C6 cells and thereby up
      regulate cytoprotective genes. Viability and cytotoxicity assays demonstrate that
      Nrf2 activation is able to protect neural cells from amyloid beta-(1-42) induced
      neurotoxicity. Down-regulation of Nrf2 by small hairpin RNA as well as
      extracellular signal-regulated kinase 1/2 inhibition abolishes cytoprotection. We
      further give evidence that kavalactone-mediated Nrf2 activation is not dependent
      on oxidative stress production. Our results demonstrate that kavalactones
      attenuate amyloid beta-peptide toxicity by inducing protective gene expression
      mediated by Nrf2 activation in vitro. These findings indicate that the use of
      purified kavalactones might be considered as an adjunct therapeutic strategy to
      combat neural demise in Alzheimer disease and other oxidative stress-related
      diseases.

PMID- 18334602
TI  - Outcomes with stroke and lateropulsion: a case-matched controlled study.
AB  - BACKGROUND AND OBJECTIVE: Lateropulsion after stroke has not been tracked using a
      case-matched controlled study and a standardized lateropulsion scale. Matched
      pairs of patients with stroke, with and without lateropulsion, were compared for
      functional outcomes and discharge destination following inpatient rehabilitation.
      METHODS: A retrospective chart review of patients with ischemic stroke at an
      inpatient rehabilitation hospital matched 36 pairs of patients with versus
      without lateropulsion. Scores of 2 or greater on the Burke Lateropulsion Scale
      identified lateropulsion. Matching criteria were side of stroke, sex, age,
      admission motor Functional Independence Measure (FIM), and interval poststroke.
      FIM efficiency (change in total FIM/length of stay) and discharge destination
      were analyzed with Wilcoxon signed-ranks tests. RESULTS: FIM efficiency and
      discharge FIM scores were lower in the lateropulsion group. Groups had similar
      mean lengths of stay. Post-hoc analyses showed that only patients with
      lateropulsion and right brain damage had significantly different FIM efficiency
      and discharge FIM scores. Lower extremity weakness was greater in the
      lateropulsion group at discharge; patients with right brain damage accounted for
      this difference. Patients with lateropulsion required more dependent living
      situations at discharge, especially if they had right brain damage. CONCLUSIONS:
      Patients with lateropulsion following stroke have a lower FIM efficiency and more
      dependency at discharge when compared with matched controls with equal functional
      limitations. Secondary analyses show worse outcomes for the subgroup of patients
      with right hemisphere stroke; lateropulsion and greater leg weakness may account
      for differences. Patients with lateropulsion may require longer rehabilitation to
      reach outcome goals.

PMID- 18334603
TI  - Reinvestment and falls in community-dwelling older adults.
AB  - BACKGROUND: Falls are common in older adults and have many adverse consequences.
      In an attempt to prevent further incidents, elder fallers may consciously monitor
      and control their movements. Ironically, conscious movement control may be one
      factor that contributes to disruption of automaticity of walking, increasing the
      likelihood of subsequent falls. OBJECTIVE: The Movement Specific Reinvestment
      Scale (MSRS), which aims to measure the propensity for movement-related self
      consciousness and for conscious processing of movement, was used to try to
      discriminate elder fallers from non-fallers. METHODS: Fifty-two volunteer older
      adults, aged 65 or above, participated. In addition to the 10-item MSRS,
      participants completed the Mini-Mental State Examination questionnaire, Timed "Up
      & Go" test, and Four Word Short-Term Memory test. Demographics including age,
      gender, and history of falling were collected. RESULTS: Elder fallers scored
      significantly higher than non-fallers on both the movement self-consciousness and
      conscious motor processing components of the MSRS. Logistic regression revealed a
      significant association between the MSRS (conscious motor processing component)
      and "faller or non-faller" status. CONCLUSIONS: Elder fallers may have a higher
      propensity to consciously control their movements. The MSRS shows potential as a
      clinical tool with which to predict falls in the elderly, as well as to gain
      insight into the perception of safety during walking in any impaired patient.

PMID- 18334604
TI  - Human adenovirus type 52: a type 41 in disguise?

PMID- 18334605
TI  - Beta-cell replication is the primary mechanism subserving the postnatal expansion
      of beta-cell mass in humans.
AB  - OBJECTIVE: Little is known about the capacity, mechanisms, or timing of growth in
      beta-cell mass in humans. We sought to establish if the predominant expansion of
      beta-cell mass in humans occurs in early childhood and if, as in rodents, this
      coincides with relatively abundant beta-cell replication. We also sought to
      establish if there is a secondary growth in beta-cell mass coincident with the
      accelerated somatic growth in adolescence. RESEARCH DESIGN AND METHODS: To
      address these questions, pancreas volume was determined from abdominal computer
      tomographies in 135 children aged 4 weeks to 20 years, and morphometric analyses
      were performed in human pancreatic tissue obtained at autopsy from 46 children
      aged 2 weeks to 21 years. RESULTS: We report that 1) beta-cell mass expands by
      severalfold from birth to adulthood, 2) islets grow in size rather than in number
      during this transition, 3) the relative rate of beta-cell growth is highest in
      infancy and gradually declines thereafter to adulthood with no secondary
      accelerated growth phase during adolescence, 4) beta-cell mass (and presumably
      growth) is highly variable between individuals, and 5) a high rate of beta-cell
      replication is coincident with the major postnatal expansion of beta-cell mass.
      CONCLUSIONS: These data imply that regulation of beta-cell replication during
      infancy plays a major role in beta-cell mass in adult humans.

PMID- 18334606
TI  - Use of anticoagulation in elderly patients with atrial fibrillation who are at
      risk for falls.
AB  - OBJECTIVE: To evaluate data addressing use of anticoagulation in elderly patients
      with atrial fibrillation (AF), in particular those at risk of falls. DATA
      SOURCES: Primary literature was identified through PubMed MEDLINE (1966-December
      2007) and EMBASE (1980-December 2007) using the search terms anticoagulation,
      warfarin, aspirin, elderly, falls, older persons, atrial fibrillation, bleeding,
      education, stroke, and use. Additional references were obtained through review of
      references from articles obtained. STUDY SELECTION AND DATA EXTRACTION: Clinical
      studies evaluating warfarin and aspirin efficacy in AF, as well as studies
      evaluating anticoagulation and falls, elderly patients, and bleeding were
      considered for inclusion. Selection emphasis was placed on randomized studies of
      AF and those evaluating anticoagulation and falls. DATA SYNTHESIS: Uncertainties
      over the optimal treatment for elderly patients with AF still exist. Variance in
      the guidelines is reflected in current practice, as some discrepancies are
      present. Warfarin is underprescribed in elderly patients, with only about 50% of
      eligible patients receiving therapy. Falls are most often cited as the reason for
      not using anticoagulants in an elderly patient. Three risk-benefit analyses have
      been performed, and all found that despite risks associated with warfarin, its
      benefits outweigh its risks even in patients who fall. Warfarin should be used
      rather than aspirin or no therapy in elderly patients at risk of falls.
      Anticoagulation education has been shown to reduce the risk of bleeding in the
      elderly and should be a vital part of warfarin management. CONCLUSIONS: The risk
      of falls alone should not automatically disqualify a person from being treated
      with warfarin. While falls should not dictate anticoagulant choice, assessment
      and management of fall risk should be an important part of anticoagulation
      management. Efforts should be made to minimize fall risk.

PMID- 18334607
TI  - Vernakalant in the management of atrial fibrillation.
AB  - OBJECTIVE: To review the pharmacology and clinical evidence of the use of
      vernakalant in the management of atrial fibrillation (AF). DATA SOURCES: Peer
      reviewed articles published in the English language were identified from MEDLINE
      and Current Contents databases (both 1966-March 5, 2008) using the search terms
      RSD 1235 and vernakalant. Citations from available articles and recent meeting
      abstracts were reviewed for additional references. During the preparation of this
      article, vernakalant was being reviewed by the Food and Drug Administration
      (FDA). Therefore, information posted on the FDA Web site was also evaluated.
      STUDY SELECTION AND DATA EXTRACTION: Phase 2 and Phase 3 clinical studies of both
      intravenous and oral vernakalant were reviewed. The design and results of the
      studies were critically evaluated. DATA SYNTHESIS: Vernakalant is a sodium and
      ultra-rapid potassium channel blocker with atrial selective effects. In 2
      clinical studies evaluating use of intravenous vernakalant in cardioversion of
      patients with recent-onset AF, vernakalant improved the chance of restoration of
      normal sinus rhythm (combined results 51% vs 3.8% with placebo; p < 0.001). In
      postoperative AF, intravenous vernakalant also improved the chance of restoration
      of normal sinus rhythm (45% vs 15% with placebo; p = 0.0002). Early Phase 2
      studies demonstrated that oral vernakalant 300 mg or 600 mg twice daily
      successfully maintained sinus rhythm compared with placebo. No proarrhythmias
      relating to vernakalant have been reported to date. Common adverse effects
      include dysgeusia, sneezing, and paresthesia. CONCLUSIONS: Vernakalant is a new
      atrial-selective antiarrhythmic agent. Phase 3 clinical trials of the intravenous
      formulation and early Phase 2 studies of the oral formulation demonstrated
      vernakalant to be efficacious and safe in converting recent-onset AF to sinus
      rhythm. Further studies are needed to explore the efficacy and safety of
      vernakalant use in patients with severe heart failure and AF, as well as its
      relative efficacy and safety compared with other antiarrhythmic agents,
      especially with long-term use.

PMID- 18334608
TI  - Myostatin, activin receptor IIb, and follistatin-like-3 gene expression are
      altered in adipose tissue and skeletal muscle of obese mice.
AB  - Myostatin (MSTN) is a secreted growth inhibitor expressed in muscle and adipose.
      We sought to determine whether expression of MSTN, its receptor activin RIIb
      (ActRIIb), or its binding protein follistatin-like-3 (FSTL3) are altered in
      subcutaneous or visceral adipose or in skeletal muscle in response to obesity.
      MSTN and ActRIIb mRNA levels were low in subcutaneous (SQF) and visceral fat (VF)
      from wild-type mice but were 50- to 100-fold higher in both SQF and VF from ob/ob
      compared with wild-type mice. FSTL3 mRNA levels were increased in SQF but
      decreased in VF in ob/ob compared with wild-type mice. Moreover, MSTN mRNA levels
      were twofold greater in tibialis anterior (TA) from ob/ob mice, whereas ActRIIb
      and FSTL3 mRNA levels were unchanged. MSTN mRNA levels were also increased in TA
      and SQF from mice on a high-fat diet. Injection of ob/ob mice with recombinant
      leptin caused FSTL3 mRNA levels to decrease in both VF and SQF in ob/ob mice;
      MSTN and ActRIIb mRNA levels tended to decrease only in VF. Finally, MSTN mRNA
      levels and promoter activity were low in adipogenic 3T3-L1 cells, but an MSTN
      promoter-reporter construct was activated in 3T3-L1 cells by cotransfection with
      the adipogenic transcription factors SREBP-1c, C/EBPalpha, and PPARgamma. These
      results demonstrate that expression of MSTN and its associated binding proteins
      can be modulated in adipose tissue and skeletal muscle by chronic obesity and
      suggest that alterations in their expression may contribute to the changes in
      growth and metabolism of lean and fat tissues occurring during obesity.

PMID- 18334609
TI  - The selective serotonin reuptake inhibitor sertraline enhances counterregulatory
      responses to hypoglycemia.
AB  - Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed for
      patients with comorbid diabetes and depression. Clinical case studies in diabetic
      patients, however, suggest that SSRI therapy may exacerbate hypoglycemia. We
      hypothesized that SSRIs might increase the risk of hypoglycemia by impairing
      hormonal counterregulatory responses (CRR). We evaluated the effect of the SSRI
      sertraline on hormonal CRR to single or recurrent hypoglycemia in nondiabetic
      rats. Since there are time-dependent effects of SSRIs on serotonin
      neurotransmission that correspond with therapeutic action, we evaluated the
      effect of 6- or 20-day sertraline treatment on hypoglycemia CRR. We found that 6
      day sertraline (SERT) treatment specifically enhanced the epinephrine response to
      a single bout of hypoglycemia vs. vehicle (VEH)-treated rats (t = 120: VEH, 2,573
      +/- 448 vs. SERT, 4,202 +/- 545 pg/ml, P < 0.05). In response to recurrent
      hypoglycemia, VEH-treated rats exhibited the expected impairment in epinephrine
      secretion (t = 60: 678 +/- 73 pg/ml) vs. VEH-treated rats experiencing first-time
      hypoglycemia (t = 60: 2,081 +/- 436 pg/ml, P < 0.01). SERT treatment prevented
      the impaired epinephrine response in recurrent hypoglycemic rats (t = 60: 1,794
      +/- 276 pgl/ml). In 20-day SERT-treated rats, epinephrine, norepinephrine, and
      glucagon CRR were all significantly elevated above VEH-treated controls in
      response to hypoglycemia. Similarly to 6-day SERT treatment, 20-day SERT
      treatment rescued the impaired epinephrine response in recurrent hypoglycemic
      rats. Our data demonstrate that neither 6- nor 20-day sertraline treatment
      impaired hormonal CRR to hypoglycemia in nondiabetic rats. Instead, sertraline
      treatment resulted in an enhancement of hypoglycemia CRR and prevented the
      impaired adrenomedullary response normally observed in recurrent hypoglycemic
      rats.

PMID- 18334610
TI  - Cross-talk between estrogen and leptin signaling in the hypothalamus.
AB  - Obesity, characterized by enhanced food intake (hyperphagia) and reduced energy
      expenditure that results in the accumulation of body fat, is a major risk factor
      for various diseases, including diabetes, cardiovascular disease, and cancer. In
      the United States, more than half of adults are overweight, and this number
      continues to increase. The adipocyte-secreted hormone leptin and its downstream
      signaling mediators play crucial roles in the regulation of energy balance.
      Leptin decreases feeding while increasing energy expenditure and permitting
      energy-intensive neuroendocrine processes, such as reproduction. Thus, leptin
      also modulates the neuroendocrine reproductive axis. The gonadal steroid hormone
      estrogen plays a central role in the regulation of reproduction and also
      contributes to the regulation of energy balance. Estrogen deficiency promotes
      feeding and weight gain, and estrogen facilitates, and to some extent mimics,
      some actions of leptin. In this review, we examine the functions of estrogen and
      leptin in the brain, with a focus on mechanisms by which leptin and estrogen
      cooperate in the regulation of energy homeostasis.

PMID- 18334611
TI  - Effect of acute physiological hyperinsulinemia on gene expression in human
      skeletal muscle in vivo.
AB  - This study was undertaken to test the hypothesis that short-term exposure (4 h)
      to physiological hyperinsulinemia in normal, healthy subjects without a family
      history of diabetes would induce a low grade inflammatory response independently
      of glycemic status. Twelve normal glucose tolerant subjects received a 4-h
      euglycemic hyperinsulinemic clamp with biopsies of the vastus lateralis muscle.
      Microarray analysis identified 121 probe sets that were significantly altered in
      response to physiological hyperinsulinemia while maintaining euglycemia. In
      normal, healthy human subjects insulin increased the mRNAs of a number of
      inflammatory genes (CCL2, CXCL2 and THBD) and transcription factors (ATF3,
      BHLHB2, HES1, KLF10, JUNB, FOS, and FOSB). A number of other genes were
      upregulated in response to insulin, including RRAD, MT, and SGK. CITED2, a known
      coactivator of PPARalpha, was significantly downregulated. SGK and CITED2 are
      located at chromosome 6q23, where we previously detected strong linkage to
      fasting plasma insulin concentrations. We independently validated the mRNA
      expression changes in an additional five subjects and closely paralleled the
      results observed in the original 12 subjects. A saline infusion in healthy,
      normal glucose-tolerant subjects without family history of diabetes demonstrated
      that the genes altered during the euglycemic hyperinsulinemic clamp were due to
      hyperinsulinemia and were unrelated to the biopsy procedure per se. The results
      of the present study demonstrate that insulin acutely regulates the levels of
      mRNAs involved in inflammation and transcription and identifies several candidate
      genes, including HES1 and BHLHB2, for further investigation.

PMID- 18334612
TI  - Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2
      diabetes.
AB  - We examined the contributions of insulin secretion, glucagon suppression,
      splanchnic and peripheral glucose metabolism, and delayed gastric emptying to the
      attenuation of postprandial hyperglycemia during intravenous exenatide
      administration. Twelve subjects with type 2 diabetes (3 F/9 M, 44 +/- 2 yr, BMI
      34 +/- 4 kg/m2, Hb A(1c) 7.5 +/- 1.5%) participated in three meal-tolerance tests
      performed with double tracer technique (iv [3-3H]glucose and oral [1
      14C]glucose): 1) iv saline (CON), 2) iv exenatide (EXE), and 3) iv exenatide plus
      glucagon (E+G). Acetaminophen was given with the mixed meal (75 g glucose, 25 g
      fat, 20 g protein) to monitor gastric emptying. Plasma glucose, insulin,
      glucagon, acetaminophen concentrations and glucose specific activities were
      measured for 6 h post meal. Post-meal hyperglycemia was markedly reduced (P <
      0.01) in EXE (138 +/- 16 mg/dl) and in E+G (165 +/- 12) compared with CON (206 +/
      15). Baseline plasma glucagon ( approximately 90 pg/ml) decreased by
      approximately 20% to 73 +/- 4 pg/ml in EXE (P < 0.01) and was not different from
      CON in E+G (81 +/- 2). EGP was suppressed by exenatide [231 +/- 9 to 108 +/- 8
      mg/min (54%) vs. 254 +/- 29 to189 +/- 27 mg/min (26%, P < 0.001, EXE vs. CON] and
      partially reversed by glucagon replacement [247 +/- 15 to 173 +/- 18 mg/min
      (31%)]. Oral glucose appearance was 39 +/- 4 g in CON vs. 23 +/- 6 g in EXE (P <
      0.001) and 15 +/- 5 g in E+G, (P < 0.01 vs. CON). The glucose retained within the
      splanchnic bed increased from approximately 36g in CON to approximately 52g in
      EXE and to approximately 60g in E+G (P < 0.001 vs. CON). Acetaminophen((AUC)) was
      reduced by approximately 80% in EXE vs. CON (P < 0.01). We conclude that
      exenatide infusion attenuates postprandial hyperglycemia by decreasing EGP (by
      approximately 50%) and by slowing gastric emptying.

PMID- 18334613
TI  - Acute and chronic ethanol consumption differentially impact pathways limiting
      hepatic protein synthesis.
AB  - This review identifies the various pathways responsible for modulating hepatic
      protein synthesis following acute and chronic alcohol intoxication and describes
      the mechanism(s) responsible for these changes. Alcohol intoxication induces a
      defect in global protein synthetic rates that is localized to impaired
      translation of mRNA at the level of peptide-chain initiation. Translation
      initiation is regulated at two steps: formation of the 43S preinitiation complex
      [controlled by eukaryotic initiation factors 2 (eIF2) and 2B (eIF2B)] and the
      binding of mRNA to the 40S ribosome (controlled by the eIF4F complex). To date,
      alcohol-induced alterations in eIF2 and eIF2B content and activity are best
      investigated. Ethanol decreases eIF2B activity when ingested either acutely or
      chronically. The reduced eIF2B activity most likely is a consequence of twofold
      increased phosphorylation of the alpha-subunit of eIF2 on Ser(51) following acute
      intoxication. The increase in eIF2alpha phosphorylation after chronic alcohol
      consumption is the same as that induced by acute ethanol intoxication, and
      protein synthesis is not further reduced by long-term alcohol ingestion despite
      additional reduced expression of initiation factors and elongation factors.
      eIF2alpha phosphorylation alone appears sufficient to maximally inhibit hepatic
      protein synthesis. Indeed, pretreatment with Salubrinal, an inhibitor of
      eIF2alpha(P) phosphatase, before ethanol treatment does not further inhibit
      protein synthesis or increase eIF2alpha phosphorylation, suggesting that acute
      ethanol intoxication causes maximal eIF2alpha phosphorylation elevation and
      hepatic protein synthesis inhibition. Ethanol-induced inhibition of hepatic
      protein synthesis is not rapidly reversed by cessation of ethanol consumption. In
      conclusion, sustained eIF2alpha phosphorylation is a hallmark of excessive
      alcohol intake leading to inhibition of protein synthesis. Enhanced
      phosphorylation of eIF2alpha represents a unique response of liver to alcohol
      intoxication, because the ethanol-induced elevation of eIF2alpha(P) is not
      observed in skeletal muscle or heart.

PMID- 18334614
TI  - Acceptance-enhanced behavior therapy (AEBT) for trichotillomania and chronic skin
      picking: exploring the effects of component sequencing.
AB  - This pilot study examined the utility of acceptance-enhanced behavior therapy
      (AEBT) for trichotillomania (TTM) and chronic skin picking (CSP) and the impact
      of altering treatment sequence on overall treatment efficacy. Participants
      referred to a TTM and CSP specialty clinic were assessed by an independent
      evaluator within separate, nonconcurrent, multiple-baseline designs across
      participants. The first group of three participants received habit-reversal
      training (HRT) followed by acceptance and commitment therapy (ACT), and the
      second group of two participants received ACT followed by HRT. Results indicated
      that AEBT greatly reduced pulling/picking for all five participants and that the
      order in which ACT and HRT were implemented made little or no difference in short
      term treatment outcome. Conclusions, limitations, and future areas of research
      are discussed.

PMID- 18334615
TI  - Pharyngeal pressure value using two continuous positive airway pressure devices.
AB  - The aim of the study was to measure the difference between the set continuous
      positive airway pressure (CPAP) value and the pharyngeal pressure reading during
      CPAP in premature infants with mild respiratory distress syndrome, using two
      different devices: hood CPAP and the conventional nasal system. The preliminary
      results suggest that hood CPAP may produce more stable pharyngeal pressure than
      the conventional nasal device.

PMID- 18334616
TI  - Developmental care: does it make a difference?
AB  - The term "Developmental Care" has been applied to a wide range of interventions.
      These may be centred on the nursing management of the infant, their environment
      or family-based interventions. The short-term targets of reducing infant stress
      and promoting stability have led to hopes that long-term neurodevelopmental
      outcomes may be improved by some or all of these practices. Thus far the paucity
      of large clinical trials consistently demonstrating positive outcomes has
      resulted in cynicism among many clinicians. However, the generally positive
      experiences of those units which have adopted many of these practices have
      contributed to the spread of these interventions in neonatal units. The emergence
      of large well-conducted clinical trials may provide the evidence to support or
      refute the outcome-based assumptions of developmental care.

PMID- 18334617
TI  - Cortical vision, MRI and developmental outcome in preterm infants.
AB  - OBJECTIVES: To test two measures of visual cortical function in the first year of
      life as early markers of functionally significant brain damage in infants born
      preterm: orientation-reversal visual event-related potentials (OR-VERP) and a
      behavioural test of cortically controlled visual attention-fixation shifts under
      competition (FS). Also to examine how these measures relate to (1) perinatal
      brain insults identified by MRI, and (2) later neurodevelopmental status.
      PATIENTS AND METHODS: After neonatal and term-age-equivalent MRI, 26 preterm
      infants (<32 weeks of gestational age, mean 28.1 weeks) were given the OR-VERP
      and FS tests before 12 months post-term age and a neurodevelopmental assessment
      (Griffiths Scales) at 2 years. MRI scans examined for parenchymal lesions,
      intraventricular haemorrhage, ventricular dilatation and diffuse excessive high
      signal intensity were classified into three categories of severity. Cortical
      visual test results were compared across these categories and examined as
      predictors of developmental status at 2 years. RESULTS: 26 infants were studied.
      13/25 infants showed significant OR-VERP responses. 12/26 showed normal FS
      performance. On both tests, the proportion of infants meeting these criteria
      decreased significantly with MRI severity. As predictors of Griffiths
      developmental quotient < or =80, the FS test had a sensitivity of 100%, a
      specificity of 61%, and positive and negative predictive values of 50% and 100%,
      respectively; corresponding values for OR-VERP were 86%, 65%, 50% and 92% .
      CONCLUSIONS: Visual cortical tests can provide early indicators of the functional
      impact of perinatal brain damage in the preterm infant.

PMID- 18334618
TI  - A systematic forward genetic analysis identified components of the Chlamydomonas
      circadian system.
AB  - The molecular bases of circadian clocks have been studied in animals, fungi,
      bacteria, and plants, but not in eukaryotic algae. To establish a new model for
      molecular analysis of the circadian clock, here we identified a large number of
      components of the circadian system in the eukaryotic unicellular alga
      Chlamydomonas reinhardtii by a systematic forward genetic approach. We isolated
      105 insertional mutants that exhibited defects in period, phase angle, and/or
      amplitude of circadian rhythms in bioluminescence derived from a luciferase
      reporter gene in their chloroplast genome. Simultaneous measurement of circadian
      rhythms in bioluminescence and growth rate revealed that some of these mutants
      had defects in the circadian clock itself, whereas one mutant had a defect in a
      specific process for the chloroplast bioluminescence rhythm. We identified 30
      genes (or gene loci) that would be responsible for rhythm defects in 37 mutants.
      Classification of these genes revealed that various biological processes are
      involved in regulation of the chloroplast rhythmicity. Amino acid sequences of
      six genes that would have crucial roles in the circadian clock revealed features
      of the Chlamydomonas clock that have both partially plant-like and original
      components.

PMID- 18334619
TI  - The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a
      potential 1p36 tumor suppressor.
AB  - VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a
      developmental apoptotic pathway that is activated when nerve growth factor (NGF)
      becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl
      hydroxylase as a downstream effector. Germline mutations of these genes cause
      familial pheochromocytoma and other neural crest-derived tumors. Using an
      unbiased shRNA screen we found that the kinesin KIF1Bbeta acts downstream from
      EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF
      becomes limiting. KIF1Bbeta maps to chromosome 1p36.2, which is frequently
      deleted in neural crest-derived tumors including neuroblastomas. We identified
      inherited loss-of-function KIF1Bbeta missense mutations in neuroblastomas and
      pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma,
      arguing that KIF1Bbeta is a pathogenic target of these deletions.

PMID- 18334620
TI  - Tel2 mediates activation and localization of ATM/Tel1 kinase to a double-strand
      break.
AB  - The kinases ATM and ATR (Tel1 and Mec1 in the yeast Saccharomyces cerevisiae)
      control the response to DNA damage. We report that S. cerevisiae Tel2 acts at an
      early step of the TEL1/ATM pathway of DNA damage signaling. We show that Tel1 and
      Tel2 interact, and that even when Tel1 protein levels are high, this interaction
      is specifically required for Tel1 localization to a DNA break and its activation
      of downstream targets. Computational analysis revealed structural homology
      between Tel2 and Ddc2 (ATRIP in vertebrates), a partner of Mec1, suggesting a
      common structural principle used by partners of phoshoinositide 3-kinase-like
      kinases.

PMID- 18334621
TI  - Sports medicine rendezvous: connecting Everest, muscle strain and sudden cardiac
      death.

PMID- 18334622
TI  - The early management of muscle strains in the elite athlete: best practice in a
      world with a limited evidence basis.

PMID- 18334623
TI  - Pistorius ineligible for the Olympic Games: the right decision.

PMID- 18334630
TI  - A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons.
AB  - Neurodegenerative diseases and noxious stimuli to the brain enhance transcription
      of serum- and glucocorticoid-induced kinase-1 (SGK1). Here, we report that the
      SGK1 gene encodes a brain-specific additional isoform, SGK1.1, which exhibits
      distinct regulation, properties, and functional effects. SGK1.1 decreases
      expression of the acid-sensing ion channel-1 (ASIC1); thereby, SGK1.1 may limit
      neuronal injury associated to activation of ASIC1 in ischemia. Given that neurons
      express at least two splice isoforms, SGK1 and SGK1.1, driven by distinct
      promoters, any changes in SGK1 transcript level must be examined to define the
      isoform induced by each stimulus or neurological disorder.

PMID- 18334631
TI  - Phenylalanine-427 of anthrax protective antigen functions in both pore formation
      and protein translocation.
AB  - The protective antigen (PA) moiety of anthrax toxin forms a heptameric pore in
      endosomal membranes of mammalian cells and translocates the enzymatic moieties of
      the toxin to the cytosol of these cells. Phenylalanine-427 (F427), a solvent
      exposed residue in the lumen of the pore, was identified earlier as being crucial
      for the transport function of PA. The seven F427 residues were shown in
      electrophysiological studies to form a clamp that catalyzes protein translocation
      through the pore. Here, we demonstrate by a variety of tests that certain F427
      mutations also profoundly inhibit the conformational transition of the heptameric
      PA prepore to the pore and thereby block pore formation in membranes. Lysine,
      arginine, aspartic acid, or glycine at position 427 strongly inhibited this
      acidic pH-induced conformational transition, whereas histidine, serine, and
      threonine had virtually no effect on this step, but inhibited translocation
      instead. Thus, it is possible to inhibit pore formation or translocation
      selectively, depending on the choice of the side chain at position 427; and the
      net inhibition of the PA transport function by any given F427 mutation is the
      product of its effects on both steps. Mutations inhibiting either or both steps
      elicited a strong dominant-negative phenotype. These findings demonstrate the
      dual functions of F427 and underline its central role in transporting the
      enzymatic moieties of anthrax toxin across membranes.

PMID- 18334632
TI  - A new influenza virus virulence determinant: the NS1 protein four C-terminal
      residues modulate pathogenicity.
AB  - The virulence of influenza virus is a multigenic trait. One determinant of
      virulence is the multifunctional NS1 protein that functions in several ways to
      defeat the cellular innate immune response. Recent large-scale genome sequence
      analysis of avian influenza virus isolates indicated that four C-terminal
      residues of the NS1 protein is a PDZ ligand domain of the X-S/T-X-V type and it
      was speculated that it may represent a virulence determinant. To test this
      hypothesis, by using mice as a model system, the four C-terminal amino acid
      residues of a number of influenza virus strains were engineered into the A/WSN/33
      virus NS1 protein by reverse genetics and the pathogenicity of the viruses
      determined. Viruses containing NS1 sequences from the 1918 H1N1 and H5N1 highly
      pathogenic avian influenza (HPAI) viruses demonstrated increased virulence in
      infected mice compared with wt A/WSN/33 virus, as characterized by rapid loss of
      body weight, decreased survival time, and decreased mean lethal dose.
      Histopathological analysis of infected mouse lung tissues demonstrated severe
      alveolitis, hemorrhaging, and spread of the virus throughout the entire lung. The
      increase in pathogenicity was not caused by the overproduction of IFN, suggesting
      the NS1 protein C terminus may interact with PDZ-binding protein(s) and modulate
      pathogenicity through alternative mechanisms.

PMID- 18334633
TI  - Human embryonic stem cell microenvironment suppresses the tumorigenic phenotype
      of aggressive cancer cells.
AB  - Embryonic stem cells sustain a microenvironment that facilitates a balance of
      self-renewal and differentiation. Aggressive cancer cells, expressing a
      multipotent, embryonic cell-like phenotype, engage in a dynamic reciprocity with
      a microenvironment that promotes plasticity and tumorigenicity. However, the
      cancer-associated milieu lacks the appropriate regulatory mechanisms to maintain
      a normal cellular phenotype. Previous work from our laboratory reported that
      aggressive melanoma and breast carcinoma express the embryonic morphogen Nodal,
      which is essential for human embryonic stem cell (hESC) pluripotency. Based on
      the aberrant expression of this embryonic plasticity gene by tumor cells, this
      current study tested whether these cells could respond to regulatory cues
      controlling the Nodal signaling pathway, which might be sequestered within the
      microenvironment of hESCs, resulting in the suppression of the tumorigenic
      phenotype. Specifically, we discovered that metastatic tumor cells do not express
      the inhibitor to Nodal, Lefty, allowing them to overexpress this embryonic
      morphogen in an unregulated manner. However, exposure of the tumor cells to a
      hESC microenvironment (containing Lefty) leads to a dramatic down-regulation in
      their Nodal expression concomitant with a reduction in clonogenicity and
      tumorigenesis accompanied by an increase in apoptosis. Furthermore, this ability
      to suppress the tumorigenic phenotype is directly associated with the secretion
      of Lefty, exclusive to hESCs, because it is not detected in other stem cell
      types, normal cell types, or trophoblasts. The tumor-suppressive effects of the
      hESC microenvironment, by neutralizing the expression of Nodal in aggressive
      tumor cells, provide previously unexplored therapeutic modalities for cancer
      treatment.

PMID- 18334634
TI  - Advantages of a single-cycle production assay to study cell culture-adaptive
      mutations of hepatitis C virus.
AB  - The JFH1 strain of hepatitis C virus (HCV) is unique among HCV isolates, in that
      the wild-type virus can traverse the entire replication cycle in cultured cells.
      However, without adaptive mutations, only low levels of infectious virus are
      produced. In the present study, the effects of five mutations that were selected
      during serial passage in Huh-7.5 cells were studied. Recombinant genomes
      containing all five mutations produced 3-4 logs more infectious virions than did
      wild type. Neither a coding mutation in NS5A nor a silent mutation in E2 was
      adaptive, whereas coding mutations in E2, p7, and NS2 all increased virus
      production. A single-cycle replication assay in CD81-deficient cells was
      developed to study more precisely the effect of the adaptive mutations. The E2
      mutation had minimal effect on the amount of infectious virus released but
      probably enhanced entry into cells. In contrast, both the p7 and NS2 mutations
      independently increased the amount of virus released.

PMID- 18334635
TI  - Profound functional and signaling changes in viable inflammatory neutrophils
      homing to cystic fibrosis airways.
AB  - Blood neutrophils recruited to cystic fibrosis (CF) airways are believed to be
      rapidly killed by resident bacteria and to passively release elastase and other
      toxic by-products that promote disease progression. By single-cell analysis, we
      demonstrate that profound functional and signaling changes readily occur within
      viable neutrophils recruited to CF airways, compared with their blood
      counterparts. Airway neutrophils have undergone conventional activation, as shown
      by decreased intracellular glutathione, increased lipid raft assembly, surface
      mobilization of CD11b+ and CD66b+ granules, and increased levels of the
      cytoskeleton-associated phospho-Syk kinase. Unexpectedly, they also mobilize to
      the surface CD63+ elastase-rich granules, usually confined intracellularly, and
      lose surface expression of CD16 and CD14, both key receptors in phagocytosis.
      Furthermore, they express CD80, major histocompatibility complex type II, and the
      prostaglandin D2 receptor CD294, all normally associated with other lineages,
      which reflects functional reprogramming. This notion is reinforced by their
      decreased total phosphotyrosine levels, mirroring a postactivated stage, and
      increased levels of the phospho-S6 ribosomal protein, a key anabolic switch.
      Thus, we identified a subset of neutrophils within CF airways with a viable but
      dysfunctional phenotype. This subset provides a possible therapeutic target and
      indicates a need to revisit current paradigms of CF airway disease.

PMID- 18334636
TI  - P-Rex2 regulates Purkinje cell dendrite morphology and motor coordination.
AB  - The small GTPase Rac controls cell morphology, gene expression, and reactive
      oxygen species formation. Manipulations of Rac activity levels in the cerebellum
      result in motor coordination defects, but activators of Rac in the cerebellum are
      unknown. P-Rex family guanine-nucleotide exchange factors activate Rac. We show
      here that, whereas P-Rex1 expression within the brain is widespread, P-Rex2 is
      specifically expressed in the Purkinje neurons of the cerebellum. We have
      generated P-Rex2(-/-) and P-Rex1(-/-)/P-Rex2(-/-) mice, analyzed their Purkinje
      cell morphology, and assessed their motor functions in behavior tests. The main
      dendrite is thinned in Purkinje cells of P-Rex2(-/-) pups and dendrite structure
      appears disordered in Purkinje cells of adult P-Rex2(-/-) and P-Rex1(-/-)/P-Rex2(
      /-) mice. P-Rex2(-/-) mice show a mild motor coordination defect that
      progressively worsens with age and is more pronounced in females than in males. P
      Rex1(-/-)/P-Rex2(-/-) mice are ataxic, with reduced basic motor activity and
      abnormal posture and gait, as well as impaired motor coordination even at a young
      age. We conclude that P-Rex1 and P-Rex2 are important regulators of Purkinje cell
      morphology and cerebellar function.

PMID- 18334637
TI  - p72 DEAD box RNA helicase is required for optimal function of the zinc-finger
      antiviral protein.
AB  - The zinc-finger antiviral protein (ZAP) specifically inhibits the replication of
      many viruses by preventing the accumulation of viral mRNAs in the cytoplasm. ZAP
      directly binds to the viral mRNAs and recruits the RNA exosome to degrade the
      target RNA. In the present study, we identified the p72 DEAD box RNA helicase,
      but not the highly similar RNA helicase p68, as a ZAP-interacting protein. The
      binding domain of ZAP was mapped to its N-terminal portion, whereas both the N-
      and C-terminal domains of p72 bound to ZAP. Overexpression of the C-terminal
      domain of p72 reduced ZAP's activity, whereas overexpression of the full-length
      p72 enhanced ZAP's activity. The RNA helicase activity was required for p72 to
      promote ZAP-mediated RNA degradation. Depletion of p72 by RNAi also reduced ZAP's
      activity but did not affect tristetraprolin-mediated RNA degradation. We conclude
      that p72 is required for the optimal activity of ZAP, and we propose that p72
      helps to restructure the ZAP-bound target mRNA for efficient degradation.

PMID- 18334638
TI  - Plants can use protein as a nitrogen source without assistance from other
      organisms.
AB  - Nitrogen is quantitatively the most important nutrient that plants acquire from
      the soil. It is well established that plant roots take up nitrogen compounds of
      low molecular mass, including ammonium, nitrate, and amino acids. However, in the
      soil of natural ecosystems, nitrogen occurs predominantly as proteins. This
      complex organic form of nitrogen is considered to be not directly available to
      plants. We examined the long-held view that plants depend on specialized
      symbioses with fungi (mycorrhizas) to access soil protein and studied the woody
      heathland plant Hakea actites and the herbaceous model plant Arabidopsis
      thaliana, which do not form mycorrhizas. We show that both species can use
      protein as a nitrogen source for growth without assistance from other organisms.
      We identified two mechanisms by which roots access protein. Roots exude
      proteolytic enzymes that digest protein at the root surface and possibly in the
      apoplast of the root cortex. Intact protein also was taken up into root cells
      most likely via endocytosis. These findings change our view of the spectrum of
      nitrogen sources that plants can access and challenge the current paradigm that
      plants rely on microbes and soil fauna for the breakdown of organic matter.

PMID- 18334639
TI  - Mycobacterial persistence requires the utilization of host cholesterol.
AB  - A hallmark of tuberculosis is the ability of the causative agent, Mycobacterium
      tuberculosis, to persist for decades despite a vigorous host immune response.
      Previously, we identified a mycobacterial gene cluster, mce4, that was
      specifically required for bacterial survival during this prolonged infection. We
      now show that mce4 encodes a cholesterol import system that enables M.
      tuberculosis to derive both carbon and energy from this ubiquitous component of
      host membranes. Cholesterol import is not required for establishing infection in
      mice or for growth in resting macrophages. However, this function is essential
      for persistence in the lungs of chronically infected animals and for growth
      within the IFN-gamma-activated macrophages that predominate at this stage of
      infection. This finding indicates that a major effect of IFN-gamma stimulation
      may be to sequester potential pathogens in a compartment devoid of more commonly
      used nutrients. The unusual capacity to catabolize sterols allows M. tuberculosis
      to circumvent this defense and thereby sustain a persistent infection.

PMID- 18334640
TI  - The protracted Holocene extinction of California's flightless sea duck (Chendytes
      lawi) and its implications for the Pleistocene overkill hypothesis.
AB  - Bones of the flightless sea duck (Chendytes lawi) from 14 archaeological sites
      along the California coast indicate that humans hunted the species for at least
      8,000 years before it was driven to extinction. Direct (14)C dates on Chendytes
      bones show that the duck was exploited on the southern California islands as
      early as approximately 11,150-10,280 calendar years B.P., and on the mainland by
      at least 8,500 calendar years B.P. The youngest direct date of 2,720-2,350
      calendar years B.P., combined with the absence of Chendytes bones from hundreds
      of late Holocene sites, suggests that the species was extinct by approximately
      2,400 years ago. Although the extinction of Chendytes clearly resulted from human
      overhunting, its demise raises questions about the Pleistocene overkill model,
      which suggests that megafauna were driven to extinction in a blitzkrieg fashion
      by Native Americans approximately 13,000 years ago. That the extermination of
      Chendytes was so protracted and archaeologically visible suggests that, if the
      terminal Pleistocene megafauna extinctions were primarily the result of human
      exploitation, there should also be a long and readily detectable archaeological
      record of their demise. The brief window now attributed to the Clovis culture (
      approximately 13,300-12,900 B.P.) seems inconsistent with an overhunting event.

PMID- 18334641
TI  - Bardet-Biedl syndrome proteins are required for the localization of G protein
      coupled receptors to primary cilia.
AB  - Primary cilia are ubiquitous cellular appendages that provide important yet not
      well understood sensory and signaling functions. Ciliary dysfunction underlies
      numerous human genetic disorders. However, the precise defects in cilia function
      and the basis of disease pathophysiology remain unclear. Here, we report that the
      proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are
      required for the localization of G protein-coupled receptors to primary cilia on
      central neurons. We demonstrate a lack of ciliary localization of somatostatin
      receptor type 3 (Sstr3) and melanin-concentrating hormone receptor 1 (Mchr1) in
      neurons from mice lacking the Bbs2 or Bbs4 gene. Because Mchr1 is involved in the
      regulation of feeding behavior and BBS is associated with hyperphagia-induced
      obesity, our results suggest that altered signaling caused by mislocalization of
      ciliary signaling proteins underlies the BBS phenotypes. Our results also provide
      a potential molecular mechanism to link cilia defects with obesity.

PMID- 18334642
TI  - The dual mode of action of bistramide A entails severing of filamentous actin and
      covalent protein modification.
AB  - This study provides comprehensive characterization of the mode of action of
      bistramide A and identifies structural requirements of bistramide-based compounds
      that are responsible for severing actin filaments and inhibiting growth of cancer
      cells in vitro and in vivo. We rationally designed and assembled a series of
      structural analogs of the natural product, including a fluorescently labeled
      conjugate. We used TIRF microscopy to directly observe actin filament severing by
      this series of small molecules, which established that the combination of the
      spiroketal and the amide subunits was sufficient to enable rapid actin filament
      disassembly in vitro. In addition, we demonstrated that the enone subunit of
      bistramide A is responsible for covalent modification of the protein in vitro and
      in A549 cells, resulting in further increase in the cytotoxicity of the natural
      product. Our results demonstrate that bistramide A elicits its potent
      antiproliferative activity by a dual mechanism of action, which entails both
      severing of actin filaments and covalent sequestration of monomeric actin in the
      cell.

PMID- 18334643
TI  - Experience is required for the maintenance and refinement of FM sweep selectivity
      in the developing auditory cortex.
AB  - Frequency modulated (FM) sweeps are common components of vocalizations, including
      human speech. How developmental experience shapes neuronal selectivity for these
      important signals is not well understood. Here, we show that altered
      developmental experience with FM sweeps used in echolocation by the pallid bat
      leads to either a loss of sideband inhibition or millisecond delays in the timing
      of inhibitory inputs, both of which lead to a reduction in rate and direction
      selectivity in auditory cortex. FM rate selectivity develops in an experience
      independent manner, but requires experience for subsequent maintenance. Direction
      selectivity depends on experience for both development and maintenance. Rate and
      direction selectivity are affected by experience over different time periods
      during development. Altered inhibition may be a general mechanism of experience
      dependent plasticity of selectivity for vocalizations.

PMID- 18334644
TI  - Possible involvement of SINEs in mammalian-specific brain formation.
AB  - Retroposons, such as short interspersed elements (SINEs) and long interspersed
      elements (LINEs), are the major constituents of higher vertebrate genomes.
      Although there are many examples of retroposons' acquiring function, none has
      been implicated in the morphological innovations specific to a certain taxonomic
      group. We previously characterized a SINE family, AmnSINE1, members of which
      constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We
      proposed that this family acquired genomic functionality or was exapted after
      retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci
      and refined 124 total loci, two of which were further analyzed. Using a mouse
      enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene
      FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8
      expression in two regions of the developing forebrain, namely the diencephalon
      and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression
      in the diencephalon controls patterning of thalamic nuclei, which act as a relay
      center of the neocortex, suggesting a role for FGF8 in mammalian-specific
      forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp
      from the gene SATB2, controls gene expression in the lateral telencephalon, which
      is thought to be a signaling center during development. These results suggest
      important roles for SINEs in the development of the mammalian neuronal network, a
      part of which was initiated with the exaptation of AmnSINE1 in a common mammalian
      ancestor.

PMID- 18334646
TI  - Long-term enhancement of skeletal muscle mass and strength by single gene
      administration of myostatin inhibitors.
AB  - Increasing the size and strength of muscles represents a promising therapeutic
      strategy for musculoskeletal disorders, and interest has focused on myostatin, a
      negative regulator of muscle growth. Various myostatin inhibitor approaches have
      been identified and tested in models of muscle disease with varying efficacies,
      depending on the age at which myostatin inhibition occurs. Here, we describe a
      one-time gene administration of myostatin-inhibitor-proteins to enhance muscle
      mass and strength in normal and dystrophic mouse models for >2 years, even when
      delivered in aged animals. These results demonstrate a promising therapeutic
      strategy that warrants consideration for clinical trials in human muscle
      diseases.

PMID- 18334645
TI  - Crystal structure of the [2Fe-2S] oxidative-stress sensor SoxR bound to DNA.
AB  - The [2Fe-2S] transcription factor SoxR, a member of the MerR family, functions as
      a bacterial sensor of oxidative stress such as superoxide and nitric oxide. SoxR
      is activated by reversible one-electron oxidation of the [2Fe-2S] cluster and
      then enhances the production of various antioxidant proteins through the soxRS
      regulon. In the active state, SoxR and other MerR family proteins activate
      transcription from unique promoters, which have a long 19- or 20-bp spacer
      between the -35 and -10 operator elements, by untwisting the promoter DNA. Here,
      we show the crystal structures of SoxR and its complex with the target promoter
      in the oxidized (active) state. The structures reveal that the [2Fe-2S] cluster
      of SoxR is completely solvent-exposed and surrounded by an asymmetric environment
      stabilized by interaction with the other subunit. The asymmetrically charged
      environment of the [2Fe-2S] cluster probably causes redox-dependent
      conformational changes of SoxR and the target promoter. Compared with the
      promoter structures with the 19-bp spacer previously studied, the DNA structure
      is more sharply bent, by approximately 1 bp, with the two central base pairs
      holding Watson-Crick base pairs. Comparison of the target promoter sequences of
      the MerR family indicates that the present DNA structure represents the activated
      conformation of the target promoter with a 20-bp spacer in the MerR family.

PMID- 18334647
TI  - A rapid upward shift of a forest ecotone during 40 years of warming in the Green
      Mountains of Vermont.
AB  - Detecting latitudinal range shifts of forest trees in response to recent climate
      change is difficult because of slow demographic rates and limited dispersal but
      may be facilitated by spatially compressed climatic zones along elevation
      gradients in montane environments. We resurveyed forest plots established in 1964
      along elevation transects in the Green Mountains (Vermont) to examine whether a
      shift had occurred in the location of the northern hardwood-boreal forest ecotone
      (NBE) from 1964 to 2004. We found a 19% increase in dominance of northern
      hardwoods from 70% in 1964 to 89% in 2004 in the lower half of the NBE. This
      shift was driven by a decrease (up to 76%) in boreal and increase (up to 16%) in
      northern hardwood basal area within the lower portions of the ecotone. We used
      aerial photographs and satellite imagery to estimate a 91- to 119-m upslope shift
      in the upper limits of the NBE from 1962 to 2005. The upward shift is consistent
      with regional climatic change during the same period; interpolating climate data
      to the NBE showed a 1.1 degrees C increase in annual temperature, which would
      predict a 208-m upslope movement of the ecotone, along with a 34% increase in
      precipitation. The rapid upward movement of the NBE indicates little inertia to
      climatically induced range shifts in montane forests; the upslope shift may have
      been accelerated by high turnover in canopy trees that provided opportunities for
      ingrowth of lower elevation species. Our results indicate that high-elevation
      forests may be jeopardized by climate change sooner than anticipated.

PMID- 18334648
TI  - A human intracranial study of long-range oscillatory coherence across a frontal
      occipital-hippocampal brain network during visual object processing.
AB  - Visual object-recognition is thought to involve activation of a distributed
      network of cortical regions, nodes of which include the lateral prefrontal
      cortex, the so-called lateral occipital complex (LOC), and the hippocampal
      formation. It has been proposed that long-range oscillatory synchronization is a
      major mode of coordinating such a distributed network. Here, intracranial
      recordings were made from three humans as they performed a challenging visual
      object-recognition task that required them to identify barely recognizable
      fragmented line-drawings of common objects. Subdural electrodes were placed over
      the prefrontal cortex and LOC, and depth electrodes were placed within the
      hippocampal formation. Robust beta-band coherence was evident in all subjects
      during processing of recognizable fragmented images. Significantly lower
      coherence was evident during processing of unrecognizable scrambled versions of
      the same. The results indicate that transient beta-band oscillatory coupling
      between these three distributed cortical regions may reflect a mechanism for
      effective communication during visual object processing.

PMID- 18334649
TI  - Isoform-specific monoubiquitination, endocytosis, and degradation of
      alternatively spliced ErbB4 isoforms.
AB  - Endocytosis and subsequent lysosomal degradation serve as a well characterized
      mechanism to fine-tune and down-regulate EGFR signaling. However, other members
      of the EGFR/ErbB receptor family have been reported to be endocytosis-impaired.
      Here we demonstrate that endocytosis of ErbB4 is regulated in an isoform-specific
      manner: CYT-1 isoforms were efficiently endocytosed whereas CYT-2 isoforms were
      endocytosis-impaired. CYT-1 isoforms in endocytic vesicles colocalized with Rab5
      and Rab7 indicating trafficking via early endosomes to late endosomal/lysosomal
      structures. A PPXY motif within the CYT-1-specific sequence that lacks from CYT-2
      was necessary both for ubiquitination and endocytosis of CYT-1 isoforms and
      provided a binding site for a WW domain-containing ubiquitin ligase Itch. Itch
      catalyzed ubiquitination of ErbB4 CYT-1, promoted its localization into
      intracellular vesicles, and stimulated degradation of ErbB4 CYT-1. Dominant
      negative Itch suppressed ErbB4 CYT-1 endocytosis and degradation. These data
      indicate that ErbB4 isoforms differ in endocytosis and degradation by a mechanism
      mediated by CYT-1-specific PPXY motif interacting with a WW domain-containing E3
      ubiquitin ligase.

PMID- 18334650
TI  - Understanding the social context of the Schelling segregation model.
AB  - A recent article [Vinkovic D, Kirman A (2006) Proc Natl Acad Sci USA 103:19261
      19265] showing that the Schelling model has a physical analogue extends our
      understanding of the model. However, prior research has already outlined a
      mathematical basis for the Schelling model and simulations based on it have
      already enhanced our understanding of the social dynamics that underlie the
      model, something that the physical analogue does not address. Research in social
      science has provided a formal basis for the segregative outcomes resulting from
      the residential selection process and simulations have replicated relevant
      spatial outcomes under different specifications of the residential dynamics. New
      and increasingly detailed survey data on preferences demonstrates the
      embeddedness of the Schelling selection process in the social behaviors of
      choosing alternative residential compositions. It also demonstrates that, in the
      multicultural context, seemingly mild preferences for living with similar
      neighbors carry the potential to be strong determinants for own race selectivity
      and residential segregation.

PMID- 18334651
TI  - Manipulation of the mechanical properties of a virus by protein engineering.
AB  - In a previous study, we showed that the DNA molecule within a spherical virus
      (the minute virus of mice) plays an architectural role by anisotropically
      increasing the mechanical stiffness of the virus. A finite element model
      predicted that this mechanical reinforcement is a consequence of the interaction
      between crystallographically visible, short DNA patches and the inner capsid
      wall. We have now tested this model by using protein engineering. Selected amino
      acid side chains have been truncated to specifically remove major interactions
      between the capsid and the visible DNA patches, and the effect of the mutations
      on the stiffness of virus particles has been measured using atomic force
      microscopy. The mutations do not affect the stiffness of the empty capsid;
      however, they significantly reduce the difference in stiffness between the DNA
      filled virion and the empty capsid. The results (i) reveal that intermolecular
      interactions between individual chemical groups contribute to the mechanical
      properties of a supramolecular assembly and (ii) identify specific protein-DNA
      interactions as the origin of the anisotropic increase in the rigidity of a
      virus. This study also demonstrates that it is possible to control the mechanical
      properties of a protein nanoparticle by the rational application of protein
      engineering based on a mechanical model.

PMID- 18334652
TI  - Unique SMAD1/5/8 activity at the phalanx-forming region determines digit
      identity.
AB  - The zone of polarizing activity is the primary signaling center controlling
      anterior-posterior patterning of the amniote limb bud. The autopodial interdigits
      (IDs) are secondary signaling centers proposed to determine digit identity by
      acting on the cells of the digital ray. Here, we focus on events accompanying
      digital fate determination and define a region of the digital ray that expresses
      Sox9 and Bmpr1b and is phosphorylated-SMAD1/5/8 (p-SMAD1/5/8) positive. We name
      this region the phalanx-forming region (PFR), and show that the PFR cells arise
      from the distal subridge mesenchyme of digital ray. This phalanx-forming cell
      lineage is subsequently committed to the cartilage lineage; the fate of these
      cells is initially labile but becomes fixed as they are incorporated into the
      condensed cartilage of the digit primordium. Using an in vivo reporter assay, we
      establish that each digital PFR has a unique p-SMAD1/5/8 activity signature. In
      addition, we show that changes in this activity correlate with the identity of
      the digit that forms after experimental manipulation, supporting the idea that
      threshold signaling levels can lead to different developmental outcomes in a
      morphogenetic field. Our data define the molecular profile of the PFR, and we
      propose a model for understanding formation and variation of digits during
      autopodial development.

PMID- 18334653
TI  - Holocene underkill.

PMID- 18334654
TI  - The "Goldilocks factor" in food webs.

PMID- 18334655
TI  - Elevated alpha-fetoprotein and a pancreatic tumour.

PMID- 18334656
TI  - Making sense of oesophageal contents.

PMID- 18334657
TI  - The significance of the gut barrier in disease.

PMID- 18334658
TI  - Genetic factors predicting response to interferon treatment for viral hepatitis
      C.

PMID- 18334659
TI  - An unusual case of ascites.

PMID- 18334660
TI  - A puzzling cause of melaena.

PMID- 18334661
TI  - An unusual ultrasound diagnosis of right lower quadrant abdominal pain.

PMID- 18334662
TI  - Colon cancer stem cells.

PMID- 18334664
TI  - Adalimumab-induced lupus erythematosus in Crohn's disease patients previously
      treated with infliximab.

PMID- 18334666
TI  - Heme oxygenase-mediated increases in adiponectin decrease fat content and
      inflammatory cytokines tumor necrosis factor-alpha and interleukin-6 in Zucker
      rats and reduce adipogenesis in human mesenchymal stem cells.
AB  - Adiponectin, an abundant adipocyte-derived plasma protein that modulates vascular
      function in type 2 diabetes, has been shown to provide cytoprotection to both
      pancreatic and vascular systems in diabetes. Therefore, we examined whether up
      regulation of heme oxygenase (HO)-1 ameliorates the levels of inflammatory
      cytokines and influences serum adiponectin in Zucker fat (ZF) rats. ZF rats
      displayed a decrease in both HO activity and HO-1 and HO-2 protein levels and an
      increase in tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 compared
      with Zucker lean (ZL) rats. Treatment of ZF animals with 2 mg/kg cobalt
      protoporphyrin IX (CoPP) increased protein levels of HO-1 and HO activity, but HO
      2 was unaffected. The increase in HO-1 was associated with a decrease in
      superoxide levels (p < 0.05) and an increase in plasma adiponectin (p < 0.005),
      compared with untreated ZF rats. CoPP treatment decreased visceral and s.c. fat
      content, and it reduced weight gain (p < 0.01). In addition, the inflammatory
      cytokines TNF-alpha and IL-6 were decreased (p < 0.04 and p < 0.008,
      respectively). Treatment of human bone marrow-derived adipocytes cultured with
      CoPP resulted in an increase in HO-1 and a decrease in superoxide levels. Up
      regulation of HO-1 caused adipose remodeling, smaller adipocytes, and increased
      adiponectin secretion in the culture medium of human bone marrow-derived
      adipocytes. In summary, this study demonstrates that the antiobesity effect of HO
      1 induction results in an increase in adiponectin secretion, in vivo and in
      vitro, a decrease in TNF-alpha and IL-6, and a reduction in weight gain. These
      findings highlight the pivotal role and symbiotic relationship of HO-1 and
      adiponectin in the modulation of the metabolic syndrome phenotype.

PMID- 18334667
TI  - Long-term but not short-term p38 mitogen-activated protein kinase inhibition
      improves cardiac function and reduces cardiac remodeling post-myocardial
      infarction.
AB  - p38 mitogen-activated protein kinase (p38 MAPK) inhibition exerts beneficial
      effects on left ventricular (LV) remodeling and dysfunction. p38 MAPK activity is
      transiently increased soon after myocardial infarction (MI), suggesting brief
      inhibition may afford the same benefit as long-term inhibition. We examined
      chronic 12-week p38 MAPK inhibition compared with short-term (7-day) inhibition,
      and then we discontinued inhibition after MI. Post-MI rats at day 7 received
      either vehicle, 4-[4-(4-fluorophenyl)-1-(3-phenylpropyl)-5-(4-pyridinyl)-1H
      imidazol-2-yl]-3-butyn-1-ol (RWJ67657; RWJ) for 12 weeks (long term; LT-RWJ), RWJ
      for 1 week and discontinued for 11 weeks (1-week RWJ), or continuous ramipril for
      12 weeks. In separate groups of animals, 24 h after MI, vehicle or RWJ was
      administered for 7 days. Cardiac function was assessed by echocardiography and
      hemodynamic measurements. Percentage of fractional shortening improved after LT
      RWJ and ramipril, but not after 1-week RWJ treatment. Likewise, LV contractility
      and maximal first derivative of left ventricular pressure (dP/dt(max)) was
      improved (12.5 and 14.4%) and LV end diastolic pressure (LVEDP) was reduced (49.4
      and 54.6%) with both treatments. Functional outcomes were accompanied by
      regression of interstitial collagen I and alpha-smooth muscle actin expression in
      LV noninfarct, border, and infarct regions with LT-RWJ and ramipril treatment.
      Hypertrophy was reduced in noninfarct (18.3 and 12.2%) and border regions (16.3
      and 12.0%) with both treatments, respectively. Animals receiving RWJ 24 h after
      MI for 7 days showed similar improvements in fractional shortening, dP/dt(max),
      LVEDP, including reduced fibrosis and hypertrophy. In vitro experiments confirmed
      a dose-dependent reduction in hypertrophy, with RWJ following tumor necrosis
      factor-alpha stimulation. Continuous but not short-term p38 MAPK blockade
      attenuates post-MI remodeling, which is associated with functional benefits on
      the myocardium.

PMID- 18334668
TI  - The AGL62 MADS domain protein regulates cellularization during endosperm
      development in Arabidopsis.
AB  - Endosperm, a storage tissue in the angiosperm seed, provides nutrients to the
      embryo during seed development and/or to the developing seedling during
      germination. A major event in endosperm development is the transition between the
      syncytial phase, during which the endosperm nuclei undergo many rounds of mitosis
      without cytokinesis, and the cellularized phase, during which cell walls form
      around the endosperm nuclei. The molecular processes controlling this phase
      transition are not understood. In agl62 seeds, the endosperm cellularizes
      prematurely, indicating that AGL62 is required for suppression of cellularization
      during the syncytial phase. AGL62 encodes a Type I MADS domain protein that
      likely functions as a transcription factor. During seed development, AGL62 is
      expressed exclusively in the endosperm. During wild-type endosperm development,
      AGL62 expression is strong during the syncytial phase and then declines abruptly
      just before cellularization. By contrast, in mutant seeds containing defects in
      some FERTILIZATION-INDEPENDENT SEED (FIS) class Polycomb group genes, the
      endosperm fails to cellularize and AGL62 expression fails to decline. Together,
      these data suggest that AGL62 suppresses cellularization during the syncytial
      phase of endosperm development and that endosperm cellularization is triggered
      via direct or indirect AGL62 inactivation by the FIS polycomb complex.

PMID- 18334669
TI  - General detoxification and stress responses are mediated by oxidized lipids
      through TGA transcription factors in Arabidopsis.
AB  - 12-oxo-phytodienoic acid and several phytoprostanes are cyclopentenone oxylipins
      that are formed via the enzymatic jasmonate pathway and a nonenzymatic, free
      radical-catalyzed pathway, respectively. Both types of cyclopentenone oxylipins
      induce the expression of genes related to detoxification, stress responses, and
      secondary metabolism, a profile clearly distinct from that of the cyclopentanone
      jasmonic acid. Microarray analyses revealed that 60% of the induction by
      phytoprostanes and 30% of the induction by 12-oxo-phytodienoic acid was dependent
      on the TGA transcription factors TGA2, TGA5, and TGA6. Moreover, treatment with
      phytoprostanes and 12-oxo-phytodienoic acid inhibited cell division and root
      growth, a property also shared by jasmonic acid. Besides being potent signals,
      cyclopentenones and other lipid peroxidation products are reactive electrophiles
      that can covalently bind to and damage proteins. To this end, we show that at
      least two of the induced detoxification enzymes efficiently metabolize
      cyclopentenones in vitro. Accumulation of two of these metabolites was detectable
      during Pseudomonas infection. The cyclopentenone oxylipin gene induction profile
      resembles the defense response induced by a variety of lipophilic xenobiotics.
      Hence, oxidized lipids may activate chemosensory mechanisms of a general broad
      spectrum detoxification network involving TGA transcription factors.

PMID- 18334670
TI  - Keratinocyte growth factor and androgen blockade work in concert to protect
      against conditioning regimen-induced thymic epithelial damage and enhance T-cell
      reconstitution after murine bone marrow transplantation.
AB  - Myeloablative conditioning results in thymic epithelial cell (TEC) injury, slow T
      cell reconstitution, and a high risk of opportunistic infections. Keratinocyte
      growth factor (KGF) stimulates TEC proliferation and, when given preconditioning,
      reduces TEC injury. Thymocytes and TECs express androgen receptors, and exposure
      to androgen inhibits thymopoiesis. In this study, we have investigated whether
      TEC stimulation via preconditioning treatment with KGF and leuprolide acetate
      (Lupron), 2 clinically approved agents, given only before conditioning would
      circumvent the profound TEC and associated T-cell deficiency seen in allogeneic
      bone marrow transplant (BMT) recipients. Only combined treatment with KGF plus
      leuprolide acetate normalized TEC subset numbers and thymic architecture.
      Thymopoiesis and thymic output were supranormal, leading to the accelerated
      peripheral reconstitution of naive CD4 and CD8 T cells with a broad Vbeta
      repertoire and decreased homeostatic T-cell proliferation. Combined therapy
      facilitated T:B cooperativity and enabled a B-cell humoral response to a CD4 T
      cell-dependent neoantigen challenge soon after BMT. In vivo antigen-specific CD8
      T-cell responses and clearance of a live pathogen was superior with combined
      versus individual agent therapy. Thus, KGF combined with androgen blockade
      represents a novel approach to restore thymic function and facilitates the rapid
      recovery of peripheral T-cell function after allogeneic BMT.

PMID- 18334671
TI  - Beyond the increasing complexity of the immunomodulatory HLA-G molecule.
AB  - Human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility
      complex (MHC) class I molecule that functions as an immunomodulatory molecule
      capable of protecting fetal tissues from the maternal immune system. The
      relevance of HLA-G in other contexts was investigated soon afterward. Numerous
      studies have sought (and some have shown) the relevance of HLA-G in pathologic
      conditions, such as transplantation, autoimmunity, and cancer and hematologic
      malignancies. One of the main goals of the current research on HLA-G is now to
      use it in the clinic, either for diagnosis or as a therapeutic tool/target. For
      this, precise knowledge on the nature and functions of HLA-G is critical. We
      highlight here what we consider are recent key basic findings on the
      immunomodulatory function of HLA-G. These strengthen the case for considering HLA
      G as clinically relevant.

PMID- 18334672
TI  - Twenty-five-year follow-up among survivors of childhood acute lymphoblastic
      leukemia: a report from the Childhood Cancer Survivor Study.
AB  - Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late
      effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n =
      5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with
      the general population and a sibling cohort (n = 3899). Cumulative mortality of
      5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483)
      and second neoplasms (SNs; n = 89) were the major causes of death. Among 185
      survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple
      chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and
      severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings.
      Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was
      21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4]
      for irradiated and nonirradiated survivors, respectively). Survivors reported
      more adverse general and mental health, functional impairment, and activity
      limitations compared with siblings (P < .001). Rates of marriage, college
      graduation, employment, and health insurance were all lower compared with sibling
      controls (P < .001). Long-term survivors of childhood ALL exhibit excess
      mortality and morbidity. Survivors who received radiation therapy as part of
      their treatment or had a leukemia relapse are at greatest risk for adverse
      outcomes.

PMID- 18334673
TI  - Targeting NF-kappaB in Waldenstrom macroglobulinemia.
AB  - The nuclear factor-kappaB (NF-kappaB) path-way has been implicated in tumor B
      cell survival, growth, and resistance to therapy. Because tumor cells overcome
      single-agent antitumor activity, we hypothesized that combination of agents that
      target differentially NF-kappaB pathway will induce significant cytotoxicity.
      Therapeutic agents that target proteasome and Akt pathways should induce
      significant activity in B-cell malignancies as both pathways impact NF-kappaB
      activity. We demonstrated that perifosine and bortezomib both targeted NF-kappaB
      through its recruitment to the promoter of its target gene IkappaB using
      chromatin immunoprecipitation assay. This combination led to synergistic
      cytotoxicity in Waldenstrom macroglobulinemia (WM) cells that was mediated
      through a combined reduction of the PI3K/Akt and ERK signaling pathways, found to
      be critical for survival of WM cells. Moreover, a combination of these drugs with
      the CD20 monoclonal antibody rituximab further increased their cytotoxic
      activity. Thus, effective WM therapy may require combination regimens targeting
      the NF-kappaB pathway.

PMID- 18334674
TI  - Heparanase regulates retention and proliferation of primitive Sca-1+/c-Kit+/Lin-
      cells via modulation of the bone marrow microenvironment.
AB  - Heparanase is involved in tumor growth and metastasis. Because of its unique
      cleavage of heparan sulfate, which binds cytokines, chemokines and proteases, we
      hypothesized that heparanase is also involved in regulation of early stages of
      hematopoiesis. We report reduced numbers of maturing leukocytes but elevated
      levels of undifferentiated Sca-1(+)/c-Kit(+)/Lin(-) cells in the bone marrow (BM)
      of mice overexpressing heparanase (hpa-Tg). This resulted from increased
      proliferation and retention of the primitive cells in the BM microenvironment,
      manifested in increased SDF-1 turnover. Furthermore, heparanase overexpression in
      mice was accompanied by reduced protease activity of MMP-9, elastase, and
      cathepsin K, which regulate stem and progenitor cell mobilization. Moreover,
      increased retention of the progenitor cells also resulted from up-regulated
      levels of stem cell factor (SCF) in the BM, in particular in the stem cell-rich
      endosteum and endothelial regions. Increased SCF-induced adhesion of primitive
      Sca-1(+)/c-Kit(+)/Lin(-) cells to osteoblasts was also the result of elevation of
      the receptor c-Kit. Regulation of these phenomena is mediated by
      hyperphosphorylation of c-Myc in hematopoietic progenitors of hpa-Tg mice or
      after exogenous heparanase addition to wildtype BM cells in vitro. Altogether,
      our data suggest that heparanase modification of the BM microenvironment
      regulates the retention and proliferation of hematopoietic progenitor cells.

PMID- 18334675
TI  - The proapoptotic and antimitogenic protein p66SHC acts as a negative regulator of
      lymphocyte activation and autoimmunity.
AB  - The ShcA locus encodes 3 protein isoforms that differ in tissue specificity,
      subcellular localization, and function. Among these, p66Shc inhibits TCR coupling
      to the Ras/MAPK pathway and primes T cells to undergo apoptotic death. We have
      investigated the outcome of p66Shc deficiency on lymphocyte development and
      homeostasis. We show that p66Shc(-/-) mice develop an age-related lupus-like
      autoimmune disease characterized by spontaneous peripheral T- and B-cell
      activation and proliferation, autoantibody production, and immune complex
      deposition in kidney and skin, resulting in autoimmune glomerulonephritis and
      alopecia. p66Shc(-/-) lymphocytes display enhanced proliferation in response to
      antigen receptor engagement in vitro and more robust immune responses both to
      vaccination and to allergen sensitization in vivo. The data identify p66Shc as a
      negative regulator of lymphocyte activation and show that loss of this protein
      results in breaking of immunologic tolerance and development of systemic
      autoimmunity.

PMID- 18334676
TI  - Lenalidomide induces complete and partial remissions in patients with relapsed
      and refractory chronic lymphocytic leukemia.
AB  - This study investigated the activity of lenalidomide in patients with
      relapsed/refractory chronic lymphocytic leukemia (CLL). Lenalidomide was given at
      10 mg daily with dose escalation up to 25 mg daily. Three patients (7%) achieved
      a complete response (CR), one a nodular partial remission, and 10 patients a
      partial remission (PR), for an overall response (OR) rate of 32%. Treatment with
      lenalidomide was associated with an OR rate of 31% in patients with 11q or 17p
      deletion, of 24% in patients with unmutated V(H), and of 25% in patients with
      fludarabine-refractory disease. The most common toxicity was myelosuppression,
      and the median daily dose of lenalidomide tolerated was 10 mg. Plasma levels of
      angiogenic factors, inflammatory cytokines, and cytokine receptors were measured
      at baseline, day 7, and day 28. There was a dramatic increase in median
      interleukin (IL)-6, IL-10, IL-2, and tumor necrosis factor receptor-1 levels on
      day 7, whereas no changes were observed in median vascular endothelial growth
      factor levels (20 patients studied). According to our experience, lenalidomide
      given as a continuous treatment has antitumor activity in heavily pretreated
      patients with CLL.

PMID- 18334677
TI  - Transgenic expression of JAK2V617F causes myeloproliferative disorders in mice.
AB  - The JAK2(V617F) mutation was found in most patients with myeloproliferative
      disorders (MPDs), including polycythemia vera, essential thrombocythemia, and
      primary myelofibrosis. We have generated transgenic mice expressing the mutated
      enzyme in the hematopoietic system driven by a vav gene promoter. The mice are
      viable and fertile. One line of the transgenic mice, which expressed a lower
      level of JAK2(V617F), showed moderate elevations of blood cell counts, whereas
      another line with a higher level of JAK2(V617F) expression displayed marked
      increases in blood counts and developed phenotypes that closely resembled human
      essential thrombocythemia and polycythemia vera. The latter line of mice also
      developed primary myelofibrosis-like symptoms as they aged. The transgenic mice
      showed erythroid, megakaryocytic, and granulocytic hyperplasia in the bone marrow
      and spleen, displayed splenomegaly, and had reduced levels of plasma
      erythropoietin and thrombopoietin. They possessed an increased number of
      hematopoietic progenitor cells in peripheral blood, spleen, and bone marrow, and
      these cells formed autonomous colonies in the absence of growth factors and
      cytokines. The data show that JAK2(V617F) can cause MPDs in mice. Our study thus
      provides a mouse model to study the pathologic role of JAK2(V617F) and to develop
      treatment for MPDs.

PMID- 18334678
TI  - Economic evaluation of continuing care interventions in the treatment of
      substance abuse: recommendations for future research.
AB  - The chronic and relapsing nature of substance abuse points to the need for
      continuing care after a primary phase of treatment. This article reviews the
      economic studies of continuing care, discusses research gaps, highlights some of
      the challenges of conducting rigorous economic evaluations of continuing care,
      and offers research guidelines and recommendations for future economic studies in
      this emerging field. Rigorous economic evaluations are needed by health care
      providers and policy makers to justify the allocation of scarce resources to
      continuing care interventions. The adoption of cost-effective continuing care
      services can reduce long-term consequences of addiction, thereby potentially
      increasing overall social welfare.

PMID- 18334679
TI  - Patient attitudes towards twin pregnancies and SET: a questionnaire study.

PMID- 18334680
TI  - The cover. Half-tide, Annisquam River.

PMID- 18334681
TI  - A piece of my mind. The only thing that matters.

PMID- 18334682
TI  - Improvements needed in management of temporomandibular joint disorders.

PMID- 18334683
TI  - FDA warns of adverse events linked to smoking cessation drug and antiepileptics.

PMID- 18334684
TI  - New evidence-based guidelines focus on treatment of children with asthma.

PMID- 18334685
TI  - Primary care screening for dementia and mild cognitive impairment.

PMID- 18334686
TI  - Primary care screening for dementia and mild cognitive impairment.

PMID- 18334687
TI  - Organ transplantation and Chagas disease.

PMID- 18334688
TI  - Plasma anandamide concentration and pregnancy outcome in women with threatened
      miscarriage.

PMID- 18334689
TI  - Comparison of strategies for sustaining weight loss: the weight loss maintenance
      randomized controlled trial.
AB  - CONTEXT: Behavioral weight loss interventions achieve short-term success, but re
      gain is common. OBJECTIVE: To compare 2 weight loss maintenance interventions
      with a self-directed control group. DESIGN, SETTING, AND PARTICIPANTS: Two-phase
      trial in which 1032 overweight or obese adults (38% African American, 63% women)
      with hypertension, dyslipidemia, or both who had lost at least 4 kg during a 6
      month weight loss program (phase 1) were randomized to a weight-loss maintenance
      intervention (phase 2). Enrollment at 4 academic centers occurred August 2003
      July 2004 and randomization, February-December 2004. Data collection was
      completed in June 2007. INTERVENTIONS: After the phase 1 weight-loss program,
      participants were randomized to one of the following groups for 30 months:
      monthly personal contact, unlimited access to an interactive technology-based
      intervention, or self-directed control. Main Outcome Changes in weight from
      randomization. RESULTS: Mean entry weight was 96.7 kg. During the initial 6-month
      program, mean weight loss was 8.5 kg. After randomization, weight regain
      occurred. Participants in the personal-contact group regained less weight (4.0
      kg) than those in the self-directed group (5.5 kg; mean difference at 30 months, 
      1.5 kg; 95% confidence interval [CI], -2.4 to -0.6 kg; P = .001). At 30 months,
      weight regain did not differ between the interactive technology-based (5.2 kg)
      and self-directed groups (5.5 kg; mean difference -0.3 kg; 95% CI, -1.2 to 0.6
      kg; P = .51); however, weight regain was lower in the interactive technology
      based than in the self-directed group at 18 months (mean difference, -1.1 kg; 95%
      CI, -1.9 to -0.4 kg; P = .003) and at 24 months (mean difference, -0.9 kg; 95%
      CI, -1.7 to -0.02 kg; P = .04). At 30 months, the difference between the personal
      contact and interactive technology-based group was -1.2 kg (95% CI -2.1 to -0.3;
      P = .008). Effects did not differ significantly by sex, race, age, and body mass
      index subgroups. Overall, 71% of study participants remained below entry weight.
      CONCLUSIONS: The majority of individuals who successfully completed an initial
      behavioral weight loss program maintained a weight below their initial level.
      Monthly brief personal contact provided modest benefit in sustaining weight loss,
      whereas an interactive technology-based intervention provided early but transient
      benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00054925.

PMID- 18334690
TI  - Universal screening for methicillin-resistant Staphylococcus aureus at hospital
      admission and nosocomial infection in surgical patients.
AB  - CONTEXT: Experts and policy makers have repeatedly called for universal screening
      at hospital admission to reduce nosocomial methicillin-resistant Staphylococcus
      aureus (MRSA) infection. OBJECTIVE: To determine the effect of an early MRSA
      detection strategy on nosocomial MRSA infection rates in surgical patients.
      DESIGN, SETTING, AND PATIENTS: Prospective, interventional cohort study conducted
      between July 2004 and May 2006 among 21 754 surgical patients at a Swiss teaching
      hospital using a crossover design to compare 2 MRSA control strategies (rapid
      screening on admission plus standard infection control measures vs standard
      infection control alone). Twelve surgical wards including different surgical
      specialties were enrolled according to a prespecified agenda, assigned to either
      the control or intervention group for a 9-month period, then switched over to the
      other group for a further 9 months. INTERVENTIONS: During the rapid screening
      intervention periods, patients admitted to the intervention wards for more than
      24 hours were screened before or on admission by rapid, multiplex polymerase
      chain reaction. For both intervention (n=10 844) and control (n=10 910) periods,
      standard infection control measures were used for patients with MRSA in all wards
      and consisted of contact isolation of MRSA carriers, use of dedicated material
      (eg, gown, gloves, mask if indicated), adjustment of perioperative antibiotic
      prophylaxis of MRSA carriers, computerized MRSA alert system, and topical
      decolonization (nasal mupirocin ointment and chlorhexidine body washing) for 5
      days. MAIN OUTCOME MEASURES: Incidence of nosocomial MRSA infection, MRSA
      surgical site infection, and rates of nosocomial acquisition of MRSA. RESULTS:
      Overall, 10 193 of 10 844 patients (94%) were screened during the intervention
      periods. Screening identified 515 MRSA-positive patients (5.1%), including 337
      previously unknown MRSA carriers. Median time from screening to notification of
      test results was 22.5 hours (interquartile range, 12.2-28.2 hours). In the
      intervention periods, 93 patients (1.11 per 1000 patient-days) developed
      nosocomial MRSA infection compared with 76 in the control periods (0.91 per 1000
      patient-days; adjusted incidence rate ratio, 1.20; 95% confidence interval, 0.85
      1.69; P = .29). The rate of MRSA surgical site infection and nosocomial MRSA
      acquisition did not change significantly. Fifty-three of 93 infected patients
      (57%) in the intervention wards were MRSA-free on admission and developed MRSA
      infection during hospitalization. CONCLUSION: A universal, rapid MRSA admission
      screening strategy did not reduce nosocomial MRSA infection in a surgical
      department with endemic MRSA prevalence but relatively low rates of MRSA
      infection. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN06603006.

PMID- 18334691
TI  - Minimally interrupted cardiac resuscitation by emergency medical services for out
      of-hospital cardiac arrest.
AB  - CONTEXT: Out-of-hospital cardiac arrest is a major public health problem.
      OBJECTIVE: To investigate whether the survival of patients with out-of-hospital
      cardiac arrest would improve with minimally interrupted cardiac resuscitation
      (MICR), an alternate emergency medical services (EMS) protocol. DESIGN, SETTING,
      AND PATIENTS: A prospective study of survival-to-hospital discharge between
      January 1, 2005, and November 22, 2007. Patients with out-of-hospital cardiac
      arrests in 2 metropolitan cities in Arizona before and after MICR training of
      fire department emergency medical personnel were assessed. In a second analysis
      of protocol compliance, patients from the 2 metropolitan cities and 60 additional
      fire departments in Arizona who actually received MICR were compared with
      patients who did not receive MICR but received standard advanced life support.
      INTERVENTION: Instruction for EMS personnel in MICR, an approach that includes an
      initial series of 200 uninterrupted chest compressions, rhythm analysis with a
      single shock, 200 immediate postshock chest compressions before pulse check or
      rhythm reanalysis, early administration of epinephrine, and delayed endotracheal
      intubation. MAIN OUTCOME MEASURE: Survival-to-hospital discharge. RESULTS: Among
      the 886 patients in the 2 metropolitan cities, survival-to-hospital discharge
      increased from 1.8% (4/218) before MICR training to 5.4% (36/668) after MICR
      training (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.1-8.9). In the
      subgroup of 174 patients with witnessed cardiac arrest and ventricular
      fibrillation, survival increased from 4.7% (2/43) before MICR training to 17.6%
      (23/131) after MICR training (OR, 8.6; 95% CI, 1.8-42.0). In the analysis of MICR
      protocol compliance involving 2460 patients with cardiac arrest, survival was
      significantly better among patients who received MICR than those who did not
      (9.1% [60/661] vs 3.8% [69/1799]; OR, 2.7; 95% CI, 1.9-4.1), as well as patients
      with witnessed ventricular fibrillation (28.4% [40/141] vs 11.9% [46/387]; OR,
      3.4; 95% CI, 2.0-5.8). CONCLUSIONS: Survival-to-hospital discharge of patients
      with out-of-hospital cardiac arrest increased after implementation of MICR as an
      alternate EMS protocol. These results need to be confirmed in a randomized trial.

PMID- 18334692
TI  - Does this patient have bacterial peritonitis or portal hypertension? How do I
      perform a paracentesis and analyze the results?
AB  - CONTEXT: Abdominal paracenteses are performed in patients with ascites, most
      commonly to assess for infection or portal hypertension and to manage refractory
      ascites. OBJECTIVES: To systematically review evidence for paracentesis methods
      that may decrease risk of adverse events or improve diagnostic yield and to
      determine the accuracy of ascitic fluid analysis for spontaneous bacterial
      peritonitis or portal hypertension. DATA SOURCES: Relevant English-language
      studies from Medline (1966-April 2007) and EMBASE (1980-April 2007). STUDY
      SELECTION: Paracentesis studies evaluating interventions (use of preprocedure
      coagulation parameters, needle type, insertion location, ultrasound guidance,
      bedside inoculation into blood culture bottles, and use of plasma expanders in
      therapeutic taps) for reducing adverse events or improving the diagnostic yield,
      and studies assessing the accuracy of ascitic fluid biochemical analyses for
      spontaneous bacterial peritonitis or portal hypertension. DATA EXTRACTION: For
      technique studies, data on intervention and outcome; and for diagnostic studies,
      data on parameters for diagnosing spontaneous bacterial peritonitis and portal
      hypertension (ie, ascitic fluid white blood cell and polymorphonuclear leukocyte
      [PMN] count, ascitic fluid pH, blood-ascitic fluid pH gradient, and serum-ascites
      albumin gradient). DATA SYNTHESIS: Thirty-seven studies met inclusion criteria: 2
      showed that obtaining preprocedure coagulation was likely unnecessary prior to
      paracentesis; 1 showed the 15-gauge, 3.25-inch needle-cannula results in less
      multiple peritoneal punctures [P = .05] and termination due to poor fluid return
      [P = .02] vs a 14-gauge needle in therapeutic paracentesis; 1 showed immediate
      inoculation of culture bottles improves diagnostic yield vs delayed (from 77% to
      100% [95% CI for the difference, 5.3%-40.0%]); 9 evaluated therapeutic
      paracentesis, performed with or without albumin or nonalbumin plasma expanders,
      and found no consistent effect on morbidity or mortality; 16 showed the accuracy
      of biochemical analysis of ascitic fluid in patients suspected of having
      spontaneous bacterial peritonitis to increase the likelihood of spontaneous
      bacterial peritonitis (PMN count >250 cells/microL [summary likelihood ratio
      {LR}, 6.4] 95% CI, 4.6-8.8; ascitic fluid leukocyte count >1000 cells/microL
      [summary LR, 9.1] 95% CI, 5.5-15.1; pH < 7.35 [summary LR, 9.0] 95% CI, 2.0-40.6;
      or a blood-ascitic fluid pH gradient > or = 0.10 [LR, 11.3] 95% CI, 4.3-29.9) and
      other levels lowered the likelihood (PMN count < or = 250 cells/microL [summary
      LR, 0.2] 95% CI, 0.11-0.37; or a blood-ascitic fluid pH gradient < 0.10 [summary
      LR, 0.12] 95% CI, 0.02-0.77); and 4 showed the diagnostic accuracy of the serum
      ascites albumin gradient lowers the likelihood of portal hypertension (< 1.1 g/dL
      [summary LR, 0.06] 95% CI, 0.02-0.20). CONCLUSIONS: Ascitic fluid should be
      inoculated into blood culture bottles at the bedside. Spontaneous bacterial
      peritonitis is more likely at predescribed parameters of ascitic PMN count or
      blood-ascitic fluid pH, and portal hypertension is less likely below a
      predescribed serum-ascites albumin gradient.

PMID- 18334693
TI  - Instant mobile communication, efficiency, and quality of life.

PMID- 18334694
TI  - The science of improvement.

PMID- 18334695
TI  - Reinventing type 2 diabetes: pathogenesis, treatment, and prevention.

PMID- 18334696
TI  - Progress in resuscitation: an evolution, not a revolution.

PMID- 18334697
TI  - Preventing MRSA infections: finding it is not enough.

PMID- 18334698
TI  - JAMA patient page. Abdominal paracentesis.

PMID- 18334699
TI  - Judah Folkman leaves expanding legacy.

PMID- 18334700
TI  - Personal genetic tests facing scrutiny.

PMID- 18334701
TI  - Electronic health records help recruit trial participants and track drug safety.

PMID- 18334702
TI  - Dietary intervention trial reports no effect on survival after breast cancer.

PMID- 18334703
TI  - Enhancing cancer registry data to promote rational health system design.

PMID- 18334704
TI  - Stat bite: Percentage of U.S. physicians using electronic health records.

PMID- 18334705
TI  - Adjuvant chemotherapy for gastric cancer or not: a dilemma?

PMID- 18334707
TI  - Solid cancer incidence in atomic bomb survivors exposed in utero or as young
      children.
AB  - BACKGROUND: In utero exposure to radiation is known to increase risks of
      childhood cancers, and childhood exposure is associated with increased risks of
      adult-onset cancers. However, little is known about whether in utero exposure to
      radiation increases risks of adult-onset cancers. METHODS: Solid cancer incidence
      rates were examined among survivors of the atomic bombings of Hiroshima and
      Nagasaki who were in utero (n = 2452) or younger than 6 years (n = 15388) at the
      time of the bombings. Poisson regression was used to estimate and compare the
      levels and temporal patterns of the radiation-associated excess risks of first
      primary solid cancers among these survivors at ages 12-55. All statistical tests
      were two-sided. RESULTS: There were 94 eligible cancers in the in utero group and
      649 in the early childhood group. The excess relative risk (ERR) increased with
      dose for both in utero (age 50, ERR = 1.0 per Sv, 95% confidence interval [CI] =
      0.2 to 2.3 per Sv) and early childhood (age 50, ERR = 1.7 per Sv, 95% CI = 1.1 to
      2.5 Sv) exposures. The ERR declined (P = .046) with increasing attained age in
      the combined cohort. Excess absolute rates (EARs) increased markedly with
      attained age among those exposed in early childhood but exhibited little change
      in the in utero group. At age 50, the estimated EARs per 10,000 person-years per
      Sv were 6.8 (95% CI = <0 to 49) for those exposed in utero and 56 (95% CI = 36 to
      79) for those exposed as young children. CONCLUSIONS: Both the in utero and early
      childhood groups exhibited statistically significant dose-related increases in
      incidence rates of solid cancers. The apparent difference in EARs between the two
      groups suggests that lifetime risks following in utero exposure may be
      considerably lower than for early childhood exposure, but further follow-up is
      needed.

PMID- 18334708
TI  - Association of a common AKAP9 variant with breast cancer risk: a collaborative
      analysis.
AB  - Data from several studies have suggested that polymorphisms in A-kinase anchoring
      proteins (AKAPs), which are key components of signal transduction, contribute to
      carcinogenesis. To evaluate the impact of AKAP variants on breast cancer risk, we
      genotyped six nonsynonymous single-nucleotide polymorphisms that were predicted
      to be deleterious and found two (M463I, 1389G>T and N2792S, 8375A>G) to be
      associated with an allele dose-dependent increase in risk of familial breast
      cancer in a German population. We extended the analysis of AKAP9 M463I, which is
      in strong linkage disequilibrium with AKAP9 N2792S, to 9523 breast cancer
      patients and 13770 healthy control subjects from seven independent European and
      Australian breast cancer studies. All statistical tests were two-sided. The
      collaborative analysis confirmed the association of M463I with increased breast
      cancer risk. Among all breast cancer patients, the combined adjusted odds ratio
      (OR) of breast cancer for individuals homozygous for the rare allele TT
      (frequency = 0.19) compared with GG homozygotes was 1.17 (95% confidence interval
      [CI] = 1.08 to 1.27, P = .0003), and the OR for TT homozygotes plus GT
      heterozygotes compared with GG homozygotes was 1.10 (95% CI = 1.04 to 1.17, P =
      .001). Among the combined subset of 2795 familial breast cancer patients, the
      respective ORs were 1.27 (95% CI = 1.12 to 1.45, P = .0003) and 1.16 (95% CI =
      1.06 to 1.27, P = .001).

PMID- 18334706
TI  - Adjuvant chemotherapy in completely resected gastric cancer: a randomized phase
      III trial conducted by GOIRC.
AB  - BACKGROUND: Complete surgical resection of gastric cancer is potentially
      curative, but long-term survival is poor. METHODS: Patients with histologically
      proven adenocarcinoma of the stomach of stages IB, II, IIIA and B, or IV (T4N2M0)
      and treated with potentially curative surgery were randomly assigned to follow-up
      alone or to intravenous treatment with four cycles (repeated every 21 days) of
      PELF (cisplatin [40 mg/m(2), on days 1 and 5], epirubicin [30 mg/m(2), days 1 and
      5], L-leucovorin [100 mg/m(2), days 1-4], and 5-fluorouracil [300 mg/m(2), days 1
      4] in a hospital setting. Frequencies and severity of adverse events were
      determined. Overall survival (OS) and disease-free survival (DFS) were compared
      between the treatment arms using Kaplan-Meier analysis and a Cox proportional
      hazards regression model. All statistical tests were two-sided. RESULTS: From
      January 1995 through September 2000, 258 patients were randomly assigned to
      chemotherapy (n = 130) or surgery alone (n = 128). Patient characteristics were
      well balanced between the two arms. Among those who received chemotherapy, grade
      3 or 4 toxic effects including vomiting, mucositis, and diarrhea were experienced
      by 21.1%, 8.4%, and 11.8% of patients, respectively. Leucopenia, anemia, and
      thrombocytopenia of grade 3 or 4 were experienced by 20.3%, 3.3%, and 4.2% of
      patients, respectively. After a median follow-up of 72.8 months, 128 patients
      (49.6%) experienced recurrence and 139 (53.9%) deaths were observed, one toxicity
      related. Relative to treatment with surgery alone, adjuvant chemotherapy did not
      increase disease-free survival (hazard ratio [HR] of recurrence = 0.92; 95%
      confidence interval [CI] = 0.66 to 1.27) or overall survival (HR of death = 0.90;
      95% CI = 0.64 to 1.26). CONCLUSIONS: Our results failed to provide proof of an
      effect of adjuvant chemotherapy with PELF on overall survival or disease-free
      survival. The estimated effect of chemotherapy (10% reduction in the hazard of
      death or relapse) is modest and consistent with the results of meta-analyses of
      adjuvant chemotherapy without platinum agents.

PMID- 18334709
TI  - Association between cyclooxygenase-2 expression in atypical hyperplasia and risk
      of breast cancer.
AB  - BACKGROUND: The cyclooxygenase-2 (COX-2) enzyme, which is induced by inflammatory
      and mitogenic stimuli, plays a protumorigenic role in several human cancers. COX
      2 is overexpressed in invasive and in situ breast cancers. Atypical hyperplasia
      in breast tissue, although benign, is associated with a high risk of breast
      cancer. We investigated whether COX-2 overexpression in atypical hyperplasia is
      associated with the risk of subsequent breast cancer. METHODS: COX-2 expression
      was assessed immunohistochemically in archival sections from 235 women with
      atypia whose biopsy specimens were obtained at the Mayo Clinic from January 1,
      1967, through December 31, 1991. COX-2 expression was scored as 0 (negative), 1+
      (weak), 2+ (moderate), or 3+ (strong). Risk factor information and follow-up for
      breast cancer events were obtained via a study questionnaire and the medical
      records. All statistical tests were two-sided. RESULTS: Forty-one (17%) of the
      235 women developed breast cancer during a median follow-up of 15 years. Moderate
      (category 2+) or strong (category 3+) COX-2 expression was identified in 71 (30%)
      and 34 (14%) of the 235 samples, respectively. The risk for developing breast
      cancer, relative to a control population (the Iowa Surveillance, Epidemiology,
      and End Results registry), increased with increasing COX-2 expression (relative
      risk [RR] = 2.63, 95% confidence interval [CI] = 1.56 to 4.15, for those with
      negative or weak COX-2 expression; RR = 3.56, 95% CI = 1.94 to 5.97, for those
      with moderate expression; and RR = 5.66, 95% CI = 2.59 to 10.75, for those with
      strong expression; P = .07). Overexpression of COX-2 was statistically
      significantly associated with the type of atypia (lobular vs ductal, P < .001),
      number of foci of atypia in the biopsy (P = .02), and older age at time of biopsy
      (>45 years, P = .01). CONCLUSIONS: COX-2 appears to be a biomarker that further
      stratifies breast cancer risk among women with atypia and may be a relevant
      target for chemoprevention strategies.

PMID- 18334710
TI  - Specialized care and survival of ovarian cancer patients in The Netherlands:
      nationwide cohort study.
AB  - BACKGROUND: There is much debate on the necessity of regionalization of ovarian
      cancer care. We investigated the association between hospital type and survival
      of patients with ovarian cancer in The Netherlands. METHODS: A retrospective,
      population-based cohort study was performed on all Dutch patients diagnosed with
      ovarian cancer from January 1, 1996, through December 31, 2003. We used data from
      the Netherlands Cancer Registry that were linked to mortality data from the
      Statistics Netherlands database to obtain the date and cause of death. Five-year
      relative survival ratios, defined as the ratio of the observed survival in the
      patient population to the expected survival of women in the general population
      with the same age, were determined for the total population and for groups
      stratified by tumor stage and/or hospital type. The association between hospital
      type and disease-specific survival was analyzed by use of multivariable Cox
      regression analyses. RESULTS: We analyzed data from 8621 women with epithelial
      ovarian cancer, of whom 3482 (40%) were treated in general hospitals, 3510 (41%)
      were treated in semispecialized hospitals, and 1557 (18%) were treated in
      specialized hospitals. Five-year relative overall survival ratios of patients
      treated in general, semispecialized, and specialized hospitals were 38.0% (95%
      confidence interval [CI] = 36.0% to 39.9%), 39.4% (95% CI = 37.5% to 41.4%), and
      40.3% (95% CI = 37.4% to 43.1%), respectively; median survival of patients aged
      50-75 years was 36 months (interquartile range [IQR] = 13 to >54 months), 37
      months (IQR = 14 to >54 months), and 38 months (IQR = 15 to >55 months),
      respectively. Age and cancer stage were associated with the relationship between
      hospital type and ovarian cancer-specific survival but histologic tumor type,
      grade, year of diagnosis, and socioeconomic status were not. Among patients with
      early-stage ovarian cancer, treatment in semispecialized and specialized
      hospitals was associated with lower risks of ovarian cancer-specific mortality
      than treatment in general hospitals. Among patients with stage I-IIA disease who
      were aged 50-75 years, risk of ovarian cancer-specific mortality was 30% and 42%
      lower after treatment in semispecialized and specialized hospitals, respectively,
      than in general hospitals (for semispecialized hospitals, hazard ratio [HR] =
      0.70, 95% CI = 0.53 to 0.93; for specialized hospitals, HR = 0.58, 95% CI = 0.38
      to 0.87). Among patients with advanced ovarian cancer, hospital type was not
      associated with survival. CONCLUSION: Hospital type was statistically
      significantly associated with survival among Dutch ovarian cancer patients with
      early-stage ovarian cancer: Patients who were treated in specialized and
      semispecialized hospitals survived longer than patients treated in general
      hospitals.

PMID- 18334711
TI  - Distinct risk factor profiles for human papillomavirus type 16-positive and human
      papillomavirus type 16-negative head and neck cancers.
AB  - BACKGROUND: High-risk types of human papillomavirus (HPV), including HPV-16,
      cause a subgroup of head and neck squamous cell carcinomas (HNSCCs). We examined
      whether the risk factors for HPV-16-positive HNSCCs are similar to those for HPV
      16-negative HNSCCs in a hospital-based case-control study. METHODS: Case subjects
      (n = 240) diagnosed with HNSCC at the Johns Hopkins Hospital from 2000 through
      2006 were stratified by tumor HPV-16 status as determined by in situ
      hybridization. Two control subjects (n = 322) without cancer were individually
      matched by age and sex to each HPV-16-positive and HPV-16-negative case subject.
      Data on risk behaviors were obtained by use of audio computer-assisted self
      interview technology. Multivariable conditional logistic regression models were
      used to estimate the odds ratios (ORs) for HPV-16-positive HNSCC and HPV-16
      negative HNSCC associated with risk factors. All statistical tests were two
      sided. RESULTS: HPV-16 was detected in 92 of 240 case subjects. HPV-16-positive
      HNSCC was independently associated with several measures of sexual behavior and
      exposure to marijuana but not with cumulative measures of tobacco smoking,
      alcohol drinking, or poor oral hygiene. Associations increased in strength with
      increasing number of oral sex partners (P(trend) = .01) and with increasing
      intensity (joints per month, P(trend) = .007), duration (in years, P(trend) =
      .01), and cumulative joint-years (P(trend) = .003) of marijuana use. By contrast,
      HPV-16-negative HNSCC was associated with measures of tobacco smoking, alcohol
      drinking, and poor oral hygiene but not with any measure of sexual behavior or
      marijuana use. Associations increased in strength with increasing intensity
      (cigarettes per day), duration, and cumulative pack-years of tobacco smoking (for
      all, P(trend) < .001), increasing years of heavy alcohol drinking (> or = 15
      years of 14 drinks per week; P(trend) = .03), and increasing number of lost teeth
      (P(trend) = .001). Compared with subjects who neither smoked tobacco nor drank
      alcohol, those with heavy use of tobacco (> or = 20 pack-years) and alcohol had
      an increased risk of HPV-16-negative HNSCC (OR = 4.8, 95% confidence interval
      [CI] = 1.8 to 12) but not of HPV-16-positive HNSCC (OR = 0.67, 95% CI = 0.29 to
      1.9). CONCLUSIONS: HPV-16-positive HNSCCs and HPV-16-negative HNSCCs have
      different risk factor profiles, indicating that they should be considered to be
      distinct cancers.

PMID- 18334712
TI  - Re: Design of phase II cancer trials using a continuous endpoint of change in
      tumor size: application to a study of sorafenib and erlotinib in non-small cell
      lung cancer.

PMID- 18334713
TI  - Re: C-reactive protein and risk of breast cancer.

PMID- 18334714
TI  - Matrix elasticity, cytoskeletal tension, and TGF-beta: the insoluble and soluble
      meet.
AB  - Soluble growth factors are potent regulators of normal and pathological
      processes. Mechanical factors are emerging as similarly important, but there has
      been no obvious mechanism linking the different factors. A recent report now
      demonstrates that cell-generated mechanical tension results in release of active
      transforming growth factor-beta from stiff extracellular matrix, providing a
      mechanism for differentiation and maintenance of myofibroblasts in processes like
      fibrosis. More broadly, the work suggests that matrix stiffness could regulate
      the equilibrium between storage and release of a host of matrix-bound growth
      factors.

PMID- 18334717
TI  - Comparing mesenchymal stromal cells from different human tissues: bone marrow,
      adipose tissue and umbilical cord blood.
AB  - Mesenchymal stromal cells (MSC) are currently in focus because of their clinical
      potential in cell therapy and tissue engineering. As yet bone marrow represents
      the main source of MSC for both experimental and clinical studies. However, it is
      speculated that the clinical value might be diminished as both the number of MSC
      and their differentiation capacity decline with age. Alternatively, MSC have been
      successfully isolated from nearly every tissue attempted so far. Our work is
      focused on comparing MSC derived from human adult bone marrow, lipoaspirate as
      well as cord blood in terms of being alternatives containing high precursor
      frequencies and youngest adult cells. Applying identical culture conditions,
      major differences were observable in the frequencies and expansion potential,
      whereas basic biological features were comparable. Since all three tissues have
      been shown to contain multipotential cells we consider aspects such as isolation
      efficacy, frequency and expansion potential may more likely affect MSC clinical
      exploitation.

PMID- 18334716
TI  - Genotype-by-diet effects on co-variation in Lp-PLA2 activity and LDL-cholesterol
      concentration in baboons fed an atherogenic diet.
AB  - Both lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity, a biomarker
      of inflammation, and concentration of its primary associated lipoprotein, LDL,
      are correlated with adverse coronary outcomes. We previously reported a
      quantitative trait locus (QTL) corresponding to HSA2p24.3-p23.2 with pleiotropic
      effects on Lp-PLA(2) activity and LDL-cholesterol (LDL-C) concentration in
      baboons fed a basal diet. Here, our goal was to locate pleiotropic QTLs
      influencing both traits in the same baboons fed a high-cholesterol, high-fat
      (HCHF) diet, and to assess whether shared genetic effects on these traits differ
      between diets. We assayed Lp-PLA(2) activity and LDL-C concentration in 683
      baboons fed the HCHF diet. We used a bivariate maximum likelihood-based variance
      components approach in whole-genome linkage screens to locate a QTL [logarithm of
      odds (LOD) = 3.13, genome-wide P = 0.019] corresponding to HSA19q12-q13.2 with
      pleiotropic effects on Lp-PLA(2) activity and LDL-C levels in the HCHF diet. We
      additionally found significant evidence of genetic variance in response to diet
      for Lp-PLA(2) activity (P = 0.0017) and for LDL-C concentration (P = 0.00001),
      revealing a contribution of genotype-by-diet interaction to covariation in these
      two traits. We conclude that the pleiotropic QTLs detected at 2p24.3-p23.2 and
      19q12-q13.2 on the basal and HCHF diets, respectively, exert diet-specific
      effects on covariation in Lp-PLA(2) activity and LDL-C concentration.

PMID- 18334715
TI  - Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease--a
      review.
AB  - Gangliosides are expressed in the outer leaflet of the plasma membrane of the
      cells of all vertebrates and are particularly abundant in the nervous system.
      Ganglioside metabolism is closely associated with the pathology of Alzheimer's
      disease (AD). AD, the most common form of dementia, is a progressive degenerative
      disease of the brain characterized clinically by progressive loss of memory and
      cognitive function and eventually death. Neuropathologically, AD is characterized
      by amyloid deposits or "senile plaques," which consist mainly of aggregated
      variants of amyloid beta-protein (Abeta). Abeta undergoes a conformational
      transition from random coil to ordered structure rich in beta-sheets, especially
      after addition of lipid vesicles containing GM1 ganglioside. In AD brain, a
      complex of GM1 and Abeta, termed "GAbeta," has been found to accumulate. In
      recent years, Abeta and GM1 have been identified in microdomains or lipid rafts.
      The functional roles of these microdomains in cellular processes are now
      beginning to unfold. Several articles also have documented the involvement of
      these microdomains in the pathogenesis of certain neurodegenerative diseases,
      such as AD. A pivotal neuroprotective role of gangliosides has been reported in
      in vivo and in vitro models of neuronal injury, Parkinsonism, and related
      diseases. Here we describe the possible involvement of gangliosides in the
      development of AD and the therapeutic potentials of gangliosides in this
      disorder.

PMID- 18334718
TI  - Clinical grade production of mesenchymal stem cells.
AB  - Mesenchymal Stem Cells (MSCs) are multipotent adult stem cells having an
      immunosuppressive effect. These characteristics lead to an increasing use of MSC
      in graft process or for regenerative medicine. For the clinical uses of MSCs,
      standards are needed. The clinical grade production necessitates adhering to good
      manufacturing practices (GMP) to insure the delivery of a "cell drug" that is
      safe, reproducible and efficient. All parts of the process must be defined: the
      starting material (tissue origin, separation or enrichment procedures), cell
      density in culture, and medium (fetal calf serum (FCS) or human serum, cytokines
      with serum-free medium for target). But to reach the GMP goal, cells have to be
      cultured in as close to a closed system as possible. Analytical methods are
      needed to assay the active compound and impurities. At a minimum, quality control
      (QC) of cells must consider the phenotype, functional potential, microbiological
      safety, and ensure the cultured cells remain untransformed. Finally, quality
      assurance system (QA) procedures specific to the production of MSCs as a cell
      drug must be determined and implemented.

PMID- 18334719
TI  - Cell therapy: a challenge in modern medicine.
AB  - Cell therapies are unique in that the active component consists of living cells,
      which are difficult to define in their pharmacologic characteristics, and which
      produce variable and largely unknown amounts of bioactive molecules. Thus, the
      definition of the composition of a cellular product, mechanisms of action,
      pharmacokinetics, toxicity and efficacy assessment represent challenges never
      previously faced by traditional pharmacology. A pressing need for a routine use
      of cell therapies in the clinic is the development of quality controls for
      efficacy on the basis of clinically relevant potency assays, with prospective
      validation in human clinical trials. This review will focus on cell-based
      protocols for joint surface repair. In particular, we will present the case of
      autologous chondrocyte implantation as an example of advanced tissue engineering
      technology in the clinic, with the assumption that many issues discussed can be
      extrapolated to other cell-based approaches in regenerative medicine.

PMID- 18334720
TI  - Chimerism analysis following nonmyeloablative stem cell transplantation using a
      new cell subset separation method: Robosep.
AB  - Chimerism analysis has become an important tool to manage patients in the peri
      transplant period of allogenic stem cell transplantation. During this period,
      cells of donor and host origin can coexist and increasing proportion of cells of
      host origin is considered as a recurrence of the underlying disease. We currently
      performed chimerism analysis on separate peripheral blood cell subsets,
      lymphocytes and granulocytes. To improve our isolation method, a new automated
      device from Stem Cell Technology Roboseptrade mark was tested and compared to our
      manual separation technique. The results obtained on T cell purification showed
      an improvement of the purity (98.42% with Robosep vs. 92.42% with the manual
      technique Rosettesep) and of the recovery (63.43% with Robosep and 38% with
      Rosettesep). The results were significantly improved on patient samples with less
      than 10% CD3 positive cells (purity: 90% vs. 44.44%; recovery: 73.79% vs.
      43.98%). Granulocytes separation was based on CD15 expression. The results showed
      an improvement of the purity with Robosep (96.90% vs. 86.20% with the manual
      technique Polymorphprep) but the recovery was impaired (35.2% vs. 52.30%). Using
      a myeloid (CD66/CD33) cocktail, recovery was improved with the Robosep device
      (64.04% with the myeloid cocktail vs. 22.4% with the CD15 cocktail). Our data
      demonstrated that Robosep allowed a performant cell purification in the early
      period post-transplantation even for populations representing less than 10% of
      the peripheral blood cells.

PMID- 18334721
TI  - Cell therapy for severe chronic heart failure: the Luxembourg experience.
AB  - Intracoronary infusion of autologous bone marrow cells (CTX) has been shown to
      improve myocardial function in post infarct patients and in patients with chronic
      ischemic cardiomyopathy. Whether CTX affects exercise-induced changes in cardiac
      deformation and mitral regurgitation (MR) in patients with end stage heart
      failure has not been studied. In this small pilot study, eleven patients with
      chronic ischemic cardiomyopathy, ejection fraction (EF) <25%, no inducible
      ischemia and heart failure class NYHA III underwent CTX. Symptom-limited bicycle
      exercise echocardiography was performed pre- and 4 months post CTX and maximum
      systolic strain (msyepsilon), peak systolic strain rate (psysr) and effective
      regurgitant orifice of MR (ERO) were determined. There were no complications
      related to the procedure. The overall clinical benefit of CTX was limited with a
      trend towards improvement (NYHA 3.0+/-0.1 pre and 2.7+/-0.2 post CTX, p=0.06).
      The EF did not improve after CTX. The wall motion score index (WMSI) did not
      change at rest but decreased significantly during exercise (1.48+/-0.16 vs.
      1.44+/-0.17, p=0.01). In conclusion, CTX may improve cardiac deformation and MR
      during exercise in patients with severe chronic heart failure when viable areas
      are targeted.

PMID- 18334722
TI  - Collagen-based biomaterials and cartilage engineering. Application to
      osteochondral defects.
AB  - Articular cartilage has a limited capacity for self-repair after trauma. Besides
      the conventional surgical techniques for repairing such defects, treatments
      involve implantation of autologous cells in suspension or within a variety of
      cell carrying scaffolds such as hyaluronic acid, alginate, agarose/alginate,
      fibrin or collagen. For the repair of full-thickness osteochondral defects,
      tissue engineers started to design single- or bi-phased scaffold constructs often
      containing hydroxyapatite-collagen composites, usually used as a bone substitute.
      The purpose of this study was to compare the behavior of bovine chondrocytes
      cultured in collagen-based scaffolds containing or not hydroxyapatite and cross
      linked following two different methods. Calf chondrocytes seeded within Hemotese
      and Collapat II sponges (SYMATESE biomaterials), chemically cross-linked with
      glutaraldehyde or EDC/NHS, were maintained up to one month in culture. The cells
      exhibited a similar behavior in the four scaffolds regarding proliferation level,
      deposition of glycosaminoglycans in the scaffolds and gene expression of types I,
      II and X collagens, aggrecan, MMP-1, -13 and the integrin subunits alpha10 and
      alpha11.

PMID- 18334723
TI  - Effect of alginate culture and mechanical stimulation on cartilaginous matrix
      synthesis of rat dedifferentiated chondrocytes.
AB  - To investigate whether the application of alginate culture and mechanical
      stimulation will improve the synthesis of cartilaginous matrix in
      dedifferentiated chondrocytes, rat chondrocytes underwent dedifferentiation upon
      serial monolayer culture up to passage 6, and then were encapsulated in 2%
      alginate gel and subject to static culture. After 28 days culture in static, the
      beads were exposed to 48 h of mechanical stimulation with continuous agitation.
      The sGAG content in alginate bead was measured by alcian blue staining. The
      expression of collagen protein was detected using immunofluorescence. After 28
      days culture in alginate bead, the dedifferentiated chondrocytes remained round
      in shape and re-synthesized the chondrocyte-specific matrix. Compared with static
      culture, mechanical stimulation induced statistically increases in the production
      of glycosaminoglycan (p< or =0.01), as well as in the synthesis of collagen type
      II protein (p< or =0.05). On the contrary, no positive expression of collagen
      type I protein was observed at the end of culture. Our results demonstrated that
      both of alginate culture and mechanical stimulation help to restore chondrocyte
      phenotype and promotes the synthesis of cartilaginous matrix.

PMID- 18334724
TI  - Cartilage tissue engineering by collagen matrix associated bone marrow derived
      mesenchymal stem cells.
AB  - In this study we compared the in vitro formation of cartilaginous grafts composed
      of collagen type I hydrogel with both ovine primary articular chondrocytes (AC)
      and bone marrow derived mesenchymal stem cells (MSC). During 4 weeks of culture,
      aggregate properties were quantitatively verified, cell viability and the
      expression of cartilage markers were assayed. Different microscopic techniques
      indicated a subdivision of MSC based scaffolds into a central construct region
      with uniformly distributed stem cells with low levels of apoptosis, and
      peripheral layers of proliferative cells, which undergo differentiation.
      Immunohistochemical staining and quantitative measurements of sulfated
      glycosaminoglycans (s-GAG) of MSC hydrogels showed a significant increase in
      matrix deposition, mainly in outer areas. Furthermore, semi-quantitative RT-PCR
      of MSC specimens reflected a constant collagen type I activity with enhanced
      collagen type II, aggrecan and Sox9 expression which would suggest hyaline-like
      cartilage formation. We propose the application of MSC seeded grafts for the
      repair of focal cartilage lesions.

PMID- 18334725
TI  - Effect of cyclic stretching and TGF-beta on the SMAD pathway in fibroblasts.
AB  - Tissue engineering requires the response of the cells to different stimuli
      inducing the synthesis of the extracellular matrix (ECM). It was been shown that
      mechanical and biochemical stimuli acted on the synthesis of ECM, particularly
      type I and III collagens. Growth factors implied in transduction pathways are
      multiple, but the main is TGF-beta. Member of the transforming growth factor-beta
      (TGF-beta) family bind to type II and type I serine/threonine kinase receptors,
      which initiate intracellular signals through activation of SMADs proteins.
      Nevertheless, the effects of mechanical stress of this pathway remain unknown.
      The aim of this work was to study the pathway of TGF-beta via the SMADs proteins
      under mechanical (stretching) and biochemical (TGF-beta) stimulations. Endogenous
      SMADs expression and its modulation by biochemical and mechanical stimulations
      were evaluated by both flow cytometry and confocal microscopy. Our results
      demonstrate that 10 ng of TGF-beta and stretching (5%, 1 Hz) applied during 15
      min induced a negative feed back loop which blocks the signalling pathway to
      control TGF-beta activity. This inhibition effect was raised after 1 h of
      stimulation. Nevertheless, these preliminary studies should be continued by study
      of expression and localization of inhibitory SMADs (SMAD7).

PMID- 18334726
TI  - Variations in the characteristics of keratocytes in culture in relation to their
      location in human cornea.
AB  - To reconstruct artificial stroma close to corneal stroma, it is necessary to use
      keratocytes with high proliferative potential that maintain the keratocyte
      phenotype as characterised by CD34. To select such cells, we tested the
      proliferative potential and characterised the keratocytes isolated from 4
      different areas of the human cornea: superior perilimbal, inferior perilimbal,
      superior central and inferior central. Keratocytes isolated from these different
      areas had significantly different growth rates (p<0.05), as measured by
      population doublings: superior perilimbal (42.59+/-11.78) > inferior perilimbal
      (38.23+/-12.67) > superior central (35.69+/-8.07) > inferior central (25.35+/
      7.63). Their clonogenic potential evolved in the same order. Moreover, CD34
      labelling gave higher levels in the central areas in relation to the perilimbal
      areas. We found the best location for isolating keratocytes for stromal
      reconstruction. The superior perilimbal area had the greatest capacity for
      proliferation, as well as the best clonogenic potential and the average CD34
      level (70%) remained high.

PMID- 18334727
TI  - In vitro effects of diacerein on NO production by chondrocytes in response to
      proinflammatory mediators.
AB  - Osteoarthritis (OA) is a progressive joint disease which represents a combination
      of several disorders leading to cartilage degradation. The production of nitric
      oxide (NO) by iNOS, which is stimulated by proinflammatory mediators, is involved
      in cartilage catabolism and should therefore be considered a potential target for
      therapeutic interventions. Diacerein is a slow-acting drug that may slow down the
      breakdown of cartilage and relieve pain and swelling. Diacerhein, in contrast to
      an NSAID, is a potent inhibitor of IL-1beta induced NO production by chondrocytes
      and cartilage. This effect appeared to result from iNOS transcriptional and/or
      post-transcriptional events, maybe by the inhibition of the NF-kappaB
      transcription factor. This paper presents results on the influence of Diacerein
      on NO production.

PMID- 18334728
TI  - Mechanical and structural assessment of cortical and deep cytoskeleton reveals
      substrate-dependent alveolar macrophage remodeling.
AB  - The sensitivity of alveolar macrophages to substrate properties has been
      described in a recent paper (Fereol et al., Cell Motil. Cytoskel. 63 (2006), 321
      340). It is presently re-analyzed in terms of F-actin structure (assessed from 3D
      reconstructions in fixed cells) and mechanical properties (assessed by Magnetic
      Twisting Cytometry experiments in living cells) of cortical and deep cytoskeleton
      structures for rigid plastic (Young Modulus: 3 MPa) or glass (70 MPa) substrates
      and a soft (approximately 0.1 kPa) confluent monolayer of alveolar epithelial
      cells. The cortical cytoskeleton component (lowest F-actin density) is
      represented by the rapid and softer viscoelastic compartment while the deep
      cytoskeleton component (intermediate F-actin density) is represented by the slow
      and stiffer compartment. Stiffness of both cortical and deep cytoskeleton is
      significantly decreased when soft confluent monolayer of alveolar epithelial
      cells replace the rigid plastic substrate while F-actin reconstructions reveal a
      consistent actin cytoskeleton remodeling observable on both cytoskeleton
      components.

PMID- 18334729
TI  - Aneuploidy and high expression of p53 and Ki67 is associated with neoplastic
      progression in Barrett esophagus.
AB  - Unless detected at an early stage, esophageal adenocarcinoma (EAC) has a poor
      prognosis. Changes in cellular DNA content and expression levels of p53 and Ki67
      in Barrett esophagus (BE) are associated with the development EAC and might serve
      as markers to identify EAC at an early stage. The aim of this study was to
      examine the presence of these three markers in various steps of neoplastic
      progression in BE towards EAC. Dysplasia was graded in 212 biopsy sets taken
      during follow-up upper endoscopy in 27 patients in whom ultimately high-grade
      dysplasia (HGD) or EAC was detected. Ploidy status was determined by flow
      cytometry, whereas Ki67 and p53 expression were determined by
      immunohistochemistry. Smoothing splines were used to analyze trends in time. We
      found an increasing fraction of Ki67 overexpression and, to a lesser extent,
      abnormal DNA content in biopsies closer to the time-point of detecting HGD/EAC in
      BE, suggesting the potential value of these biomarkers in identifying patients at
      increased risk of progression towards HGD/EAC. Accumulation of p53 was seen
      several years before development of HGD/EAC, and may therefore be an early marker
      in BE at a stage when dysplasia is not yet detected. A prospective follow-up
      study is needed to confirm these findings.

PMID- 18334730
TI  - Complete mutation screening and haplotype characterization of BRCA1 gene in
      Tunisian patients with familial breast cancer.
AB  - Breast cancer, the most commonly diagnosed cancer in women, is the second leading
      cause of cancer death in women worldwide. To investigate the contribution of
      BRCA1 gene mutations to familial breast cancer in Tunisia, 32 unrelated patients
      who had at least one first degree relative affected with breast and/or ovarian
      cancer were analysed. BRCA1 mutation analysis was performed by DNA sequencing of
      all BRCA1 exons. We identified four different BRCA1 frameshift mutations:
      c.4041delAG, c.2551delG and c.5266dupC already been described and one novel
      mutation, c.211dupA, observed in two unrelated families. C.5266dupC has
      previously been found among Jewish Ashkenazi and Eastern European populations.
      Our study describes it in Arabic/Berber population. Five out of thirty two
      familial cases had deleterious BRCA1 mutations. Fifteen additional cases carried
      unclassified variants (UV) or single nucleotide polymorphisms (SNPs). Our study
      is the first molecular investigation on the role of BRCA1 in hereditary breast
      cancer in North Tunisia.

PMID- 18334731
TI  - The degree of readiness of selected biomarkers for the early detection of
      hepatocellular carcinoma: notes from a recent workshop.
AB  - This opinion piece evaluates the degree of readiness of 13 candidate biomarkers
      or panels of biomarkers for the early detection of hepatocellular carcinoma
      (HCC), or for the staging of liver fibrosis. As candidate biomarkers for the
      early detection of disease are identified, it is important to understand where
      they are in the developmental pipeline and how they might be employed. HCC is a
      growing public health problem, and its early detection is believed to be
      important in its management. Current detection methods are limited in usefulness
      or practicality, and there is a need for better methods to diagnose liver
      disease. Therefore, a number of candidate biomarkers, considered to be attractive
      because of their advanced stage of development or inherent scientific value, were
      evaluated for specificity and sensitivity for detection of liver disease. Study
      design, confirmatory evidence and assay practicality associated with each of the
      biomarkers are considered. The comments in this review reflect the authors'
      opinions and are based on a recent workshop convened by the Hepatitis B
      Foundation of America and the US National Cancer Institute's Early Detection
      Research Network. It is emphasized that only a selected set of biomarkers was
      considered; thus, this review is not comprehensive and not intended to review all
      candidate HCC biomarkers.

PMID- 18334732
TI  - Glycoforms of CA125 antigen as a possible cancer marker.
AB  - CA125, a coelomic epithelium-related antigen, is expressed in both normal and
      pathological conditions. In this study, we compared the glycosylation of CA125
      antigen from amniotic fluid and the ovarian carcinoma cell line OVCAR-3, in order
      to detect possible differences as a specific marker of their origin. Antigens
      from both sources were radiolabelled and subsequently subjected to the affinity
      chromatography, using plant lectins differing in carbohydrate specificity as
      ligands. A common chromatographic scheme was applied to all columns, i.e. they
      were eluted with: a) washing buffer to wash out non-bound and low-affinity bound
      fractions, b) a solution of inhibitory sugar and c) a low pH buffer, to release
      the high affinity bound fractions. CA125 antigen from each source was found to be
      heterogeneous in respect to the existence of multiple glycoforms, with O-linked
      glycan chains predominating. However, the binding patterns of both N- and O
      linked glycan-reactive lectins indicated distinct differences in carbohydrate
      composition between CA125 antigen isolated from amniotic fluid and OVCAR-3 cell
      line. The observed specificites of CA125-oligosaccharide chains might be of
      special importance from the biomedical aspect, in terms of their possible use for
      clinical evaluation of gynecological functions in health and disease.

PMID- 18334733
TI  - Soluble cytokeratin-19 and E-selectin biomarkers: their relevance for lung cancer
      detection when tested independently or in combinations.
AB  - OBJECTIVES: Determination of tumor biomarkers in serum has been proposed as an
      alternative and noninvasive way of establishing diagnosis for lung cancer. The
      aim of this study was to assess the combined use of Cyfra 21-1; the soluble
      fragment of cytokeratin 19, and soluble E-selectin; endothelial adhesion
      molecule, for improving the accuracy of diagnosing and screening lung cancer.
      MATERIALS AND METHODS: Serum Cyfra 21-1 and sE-selectin were determined using
      electrochemiluminescent immunoassay and enzyme linked immunosorbent assay,
      respectively, in 52 patients with histologically proven lung cancer, 40 patients
      with benign lung diseases and 50 healthy volunteers. RESULTS: Both markers were
      significantly increased in lung cancer patients as compared to healthy, for
      benign lung diseases Cyfra 21-1 perform well than sE-selectin. Sensitivities of
      Cyfra 21-1 and sE-selectin at 95th percentiles of the normal group were 96.2% and
      92.3%, while at 95th percentiles of the benign lung diseases were 57.7% and 5%,
      respectively. In ROC curves, the diagnostic power for the detection of lung
      cancer was similar for Cyfra 21-1 and sE-selectin; however, when compared with
      benign lung diseases, Cyfra 21-1 was superior to sE-selectin. The highest
      sensitivity (99.8%) was reported when the two markers were combined. CONCLUSION:
      Cyfra 21-1 and sE-selectin show good performance in detecting lung cancer from
      normal groups, however, Cyfra 21-1 was superior to sE-selectin in discriminating
      lung cancer from benign lung diseases.

PMID- 18334734
TI  - Transcriptionally less active prodynorphin promoter alleles are associated with
      temporal lobe epilepsy: a case-control study and meta-analysis.
AB  - We performed an association study in a population of patients with Mesial
      Temporal Lobe Epilepsy (TLE) with Hippocampal Sclerosis (MTEHS) together with a
      systematic revision of the literature to investigate the role of
      transcriptionally less active polymorphic alleles of Prodynorphin (PDYN) gene in
      this pathology. We included 102 patients with a diagnosis of MTEHS and 86 healthy
      controls. The positive antecedent of family history for epileptic events defined
      a TLE subgroup with familial predisposition for epileptic disorders. The PDYN
      promoter polymorphism was genotyped by means of a PCR assay. For meta-analysis,
      we identified case-control association studies between TLE and PDYN by searching
      PUBMED. The pooled OR was estimated using a fixed effects model under dominant
      and co-dominant heredity models. No differences in genotypic and allelic
      frequencies were found between cases and controls (p=0.61) in our population,
      neither in the whole cohort nor in the analysis limited to TLE with familial
      predisposition (p=0.71). The Meta-Analysis included 591 TLE patients and 1117
      healthy controls. We found an association between L allele (p=0.003; OR=1.40; IC
      95=1.12-1.74) and a modestly higher risk to develop TLE in the group of patients
      with familial predisposition. Therefore, functional allelic variants in the PDYN
      promoter might modify the risk to develop TLE in subjects with familial
      predisposition.

PMID- 18334735
TI  - Elevation in peripheral blood circulating tumor cell number correlates with
      macroscopic progression in UICC stage IV colorectal cancer patients.
AB  - AIMS: Cytokeratin(CK) based real-time RT-PCR assays (QRT-PCR) are now available
      for peripheral blood circulating tumor cell (CTC) evaluations in colorectal
      cancer(CRC) patients. Results are non-existent for the application of these
      techniques to the determination of progression and therapy response in Dukes
      stage D CRC patients. PATIENTS AND METHODS: Each month 30 ml peripheral blood of
      30 Dukes D patients (17 with progression) were drawn. CEA, CA19-9, CA72-A and TPA
      M determinations were made. CK20, thymidilate synthase(TS) QRT-PCR was performed,
      as well. Buffy coat was used for immunmagnetic cancer cell isolation and CTC
      counting. Correlation between elevated CTC and macroscopic progression within 3
      months was determined by Chi2 test. RESULTS: Microscopic CTC single cell,
      doublet, cluster number were found in correlation with CK20 QRT-PCR results (p<
      0.01). There was a significant increase in microscopic CTC number, CK20 and
      decrease in TS QRT-PCR levels (p< 0.05) in the peripheral blood of the non
      responder as compared to responder patients. Elevation of the CTC was in
      significant correlation with macroscopic progression of the disease in 3 months
      (p< 0.01). CONCLUSIONS: CTC number reflects the chemotherapeutic sensitivity of
      CRC patients. Elevation of circulating tumor cell number in peripheral blood is
      in correlation with macroscopic progression.

PMID- 18334736
TI  - Detection of membrane fluidity in submitochondrial particles of platelets and
      erythrocyte membranes from Mexican patients with Alzheimer disease by
      intramolecular excimer formation of 1,3 dipyrenylpropane.
AB  - It has been suggested that mitochondrial dysfunction and defects in membrane
      structure could be implied in AD pathogenesis. The aim of the present work was
      the study of membrane fluidity in submitochondrial platelet particles and
      erythrocyte membranes from Mexican patients. Blood samples were obtained from 30
      patients with Alzheimer disease and 30 aged-matched control subjects. Membrane
      fluidity determinations were done using a very low concentration of the
      fluorescent dipyrenylpropane probe incorporated in both types of membranes. This
      probe is able to give excimer and monomer fluorescence, therefore it can be used
      to monitor fluidity changes in biological membranes. The data obtained showed
      that in submitochondrial particles from AD patients, the excimer to monomer
      fluorescent intensity ratio was lower (0.231 +/- 0.008) than aged-matched control
      subjects (0.363 +/- 0.014). Therefore, membrane fluidity was lower in AD samples.
      On the other hand, we found similar membrane fluidity in erythrocytes from AD
      patients and aged-matched controls: the fluorescent intensity ratios were 0.312
      +/- 0.03 and 0.305 +/- 0.033, respectively. In addition, lipid peroxidation in
      submitochondrial particles and erythrocyte membranes was higher in AD samples
      than in aged-matched controls. These data suggest that submitochondrial platelet
      particles are more sensitive to oxidative stress than erythrocyte membranes.

PMID- 18334737
TI  - An increase in N-Ras expression is associated with development of hormone
      refractory prostate cancer in a subset of patients.
AB  - Protein expression of H, K and N-Ras was assessed in hormone sensitive and
      hormone refractory prostate tumour pairs from 61 patients by
      immunohistochemistry. Expression of H-Ras and K- Ras was not associated with any
      known clinical parameters. In contrast an increase in N-Ras membrane expression
      in the transition from hormone sensitive to hormone refractory prostate cancer
      was associated with shorter time to relapse (p=0.01) and shorter disease specific
      survival (p=0.008). In addition, patients with an increase in N-Ras membrane
      expression had lower levels of PSA at relapse (p=0.02) and expression correlated
      with phosphorylated MAP kinase (p=0.010) and proliferation index (Ki67, p=0.02).
      These results suggest that in a subgroup patients N-Ras expression is associated
      with development of hormone refractory prostate cancer via activation of the MAP
      kinase cascade.

PMID- 18334738
TI  - Polymorphisms of the fibrinogen-beta gene are related to 2-hour glucose level
      after oral glucose tolerance test in Hong Kong Chinese.
AB  - Fibrinogen, an acute phase protein, is an important inflammatory marker that is
      associated with cardiovascular diseases. We studied the association of three
      common human fibrinogen-beta gene (FGB) variants, -455G>A, -249C>T, and -148C>T
      with glycemic parameters in 265 non-diabetic Hong Kong Chinese subjects. Both FGB
      variants, -455G>A and -148C>T were in complete linkage disequilibrium and were
      associated with higher levels of plasma fibrinogen and 2-h glucose after a 75-g
      oral glucose load (p<0.01). Carriers of FGB AC-haplotype, comprising the two
      nucleotide variants at positions -455 and -249, had higher fibrinogen level (2.64
      +/- 0.65 vs 2.42 +/- 0.52 g/L, p=0.002) and 2-h glucose after a 75-g oral glucose
      load (5.87 +/- 1.14 vs 5.47 +/- 1.22 g/L, p=0.006). The associations were
      significant in men, but not women. In stepwise multiple regression analysis, AC
      haplotype was independently associated with plasma fibrinogen level and 2-h
      glucose (p=0.002 and 0.010 respectively). This suggests that fibrinogen may play
      a role in the development of impaired glucose tolerance.

PMID- 18334739
TI  - C-338A polymorphism of the endothelin-converting enzyme (ECE-1) gene and the
      susceptibility to sporadic late-onset Alzheimer's disease and coronary artery
      disease.
AB  - The human endothelin-converting enzyme (ECE) is involved in beta-amyloid
      synthesis and regulation of the endothelin-1 (ET-1) vasoconstricting peptide. We
      investigated the distribution of the C-338A polymorphism of the ECE-1b gene in
      sporadic late-onset Alzheimer's disease (LOAD) and in coronary artery disease
      (CAD) to verify its role in the onset of these two complex diseases. Two cohorts
      of 458 Italian Caucasian LOAD patients and 165 CAD patients were examined for the
      C-338A polymorphism and compared with respective control samples (260 and 106
      subjects, respectively) . The A allele was less present in LOAD patients than in
      controls, but an at limits statistically significant difference was achieved only
      in subjects aged less than 80 years, where only the AA genotypes appeared to have
      a protective role against the onset of the sporadic LOAD. For the overall CAD
      sample the pattern was similar and significant differences were observed only in
      subjects non carrying the apolipoprotein E (APOE) e*4 allele, where the A allele
      carrying genotypes had a protective role against the onset of the disease.

PMID- 18334740
TI  - Mast cells, TGF-beta1 and alpha-SMA expression in IgA nephropathy.
AB  - IgA nephropathy (IgAN) is a kidney disease with a varying renal prognosis.
      Recently, many studies have demonstrated that renal alpha-smooth muscle actin
      (alpha-SMA) and transforming growth factor (TGF-beta1) expression, as well
      interstitial mast cell infiltrates could represent a prognostic marker in several
      renal diseases. The aim of our study was to analyze the prognostic value of mast
      cell, TGF-beta1 and alpha-SMA expression in IgAN. A survey of the medical records
      and renal biopsy reports of 62 patients with a diagnosis of IgAN followed-up from
      1987 to 2003 was performed. The mean follow-up time was 74.7 +/- 50.0 months. The
      immunohistochemical studies were performed using a monoclonal antibody anti-human
      mast cell tryptase, a polyclonal antibody anti-human TGF-beta1, and a monoclonal
      antibody anti-human alpha-SMA. An unfavorable clinical course of IgAN was related
      to interstitial mast cell infiltrates and alpha-SMA expression in the
      tubulointerstitial area. Expression of glomerular TGF-beta1 and alpha-SMA, and
      interstitial TGF-beta1 is not correlated with clinical course in IgAN. In
      conclusion, the increased number of mast cells and higher alpha-SMA expression in
      the tubulointerstitial area may be predictive factors for the poor prognosis of
      patients with IgAN.

PMID- 18334741
TI  - Determination of glutamic acid decarboxylase (GAD65) in pancreatic islets and its
      in vitro and in vivo degradation kinetics in serum using a highly sensitive
      enzyme immunoassay.
AB  - Glutamic acid decarboxylase GAD65 autoantibodies (GADA) are an established marker
      for autoimmune diabetes. Recently, the autoantigen GAD65 itself was proposed as
      biomarker of beta-cell loss for prediction of autoimmune diabetes and graft
      rejection after islet transplantation. Therefore, the GAD65 content in pancreatic
      islets of different species and its serum degradation kinetics were examined in
      this study using a sensitive immunoassay. GAD65 was found in quantities of 78
      (human), 43.7 (LEW.1A rat) and 37.4 (BB/OK rat) ng per 1,000 islets,
      respectively, but not in mouse islets. The in vitro half-life of porcine GAD65
      and human recombinant GAD65 ranged from 1.27 to 2.35 hours at 37 degrees C in
      human serum, plasma and blood, and was unaffected by presence of GAD65
      autoantibodies. After injecting 2,000 ng recombinant human GAD65 into LEW.1A
      rats, the in vivo half-life was 2.77 hours. GAD65 was undetectable after 24 hours
      in these animals, and for up to 48 hours following diabetes induction by
      streptozotocin in LEW.1A rats. Estimated from these data, at least 13 islets in
      rat and 1,875 in human must be simultaneously destroyed to detect GAD65 in
      circulation. These results should be taken into consideration in further studies
      aimed at examining the diagnostic relevance of GAD65.

PMID- 18334742
TI  - Production of effective luteinizing hormone antisera by two immunization methods.
AB  - This paper addresses the production of effective luteinizing hormone antisera by
      two different immunization methods; the traditional and modified methods. The
      main difference between these two methods is in the immunization procedure. In
      the modified method, an additional injection of emulsion with complete Freund's
      adjuvant and only one booster are applied at the third and 28th day from the
      first injection, respectively. The results of the study indicated the possibility
      of producing the antiseria using the modified method in short time and better
      quality than those produced by the traditional methods. The details of both
      methods are presented together with the results obtained from the antibodies
      detection. Comparison between these two methods is also presented along with
      discussions.

PMID- 18334743
TI  - A recombinant human monoclonal anti-R7V antibody as a potential therapy for HIV
      infected patients in failure of HAART.
AB  - The construction of a recombinant antibody directed against the cellular epitope
      R7V acquired by HIV during the viral budding has been realized. The c-DNAs
      encoding the variable regions of the anti-R7V antibody have been cloned from B
      lymphocytes of a non-progressor patient. Two transfer vectors containing complete
      coding sequences for heavy and light chains of this antibody were constructed and
      a recombinant baculovirus was generated by a double recombination between
      baculovirus DNA and the two transfer vectors. Insect cells infected with this
      baculovirus produced a complete human anti-R7V immunoglobulin. This recombinant
      antibody, specific to the R7V peptide, recognizes and neutralizes all clades of
      HIV1 including resistant viruses, opening new perspectives in anti-HIV therapy.

PMID- 18334744
TI  - Cocktails of human anti-cancer antibodies show a synergistic effect in nude mouse
      tumor xenografts.
AB  - A panel of four natural human monoclonal IgG antibodies derived from B
      lymphocytes isolated from regional draining lymph nodes of cancer patients has
      been developed and characterized. The four human antibodies are termed, RM1, RM2,
      RM3, and RM4. The immunoreactivity of this panel of four human antibodies is
      restricted to tumor cells. Individually, these human MAbs show tumor targeting
      and are effective in inhibiting tumor growth in nude mouse xenograft models. When
      used in combination the antibodies show an additive effect in slowing down the
      progression of tumors in xenograft models suggesting that cocktails of antibodies
      may be useful in the clinic.

PMID- 18334745
TI  - A human antibody against anthrax protective antigen protects rabbits from lethal
      infection with aerosolized spores.
AB  - ALXN4100, a fully human antibody that binds to the protective antigen of anthrax
      toxin, was generated from a Fab isolated from a phage display library and was
      analyzed for its pharmacokinetic properties in rabbits and then used to protect
      rabbits from challenge with a lethal aerosol dose of Bacillus anthracis spores
      (approximately 322X LD(50)). All rabbits receiving 15 or 40 mg/kg of antibody 24
      hours before challenge survived; survival of rabbits receiving 4 mg/kg either
      subcutaneously or intravenously was 80 or 90%, respectively. Susceptibility to
      anthrax disease appeared to be correlated with serum antibody concentration. This
      study indicates that ALXN4100 has the potential to be useful for prophylaxis of
      anthrax disease in humans.

PMID- 18334746
TI  - APAAP complex: production and usage in immunocytochemical and immunohistochemical
      staining.
AB  - BACKGROUND: The affinity of antibody to antigen, in addition to providing the
      possibility of measuring the antigen in tissue extracts through methods such as
      RIA (Radioimmunoassay) and EIA (Enzymimmunoassay) and possibility of isolating
      and analyzing dispersed cell colonies using flowcytometry, makes it possible to
      determine the site of antigen in tissues (Immunohistochemistry) or in cells
      (Immunocytochemistry). OBJECTIVE: Production of APAAP complexes and comparing
      them with similar foreign products to determine the site of antigen in tissues or
      in cells. METHODS: Secreted antibodies of the two hybridomas (A(1)G(9)G(3) and
      A(1)G(8)F(7) produced in our laboratory) were concentrated, purified and
      characterized. Then the monoclonal antibodies were mixed with alkaline
      phosphatase enzyme (ALP) to use in immunocytochemistry (ICC) and
      immunohistochemistry (IHC) staining. RESULTS: Both of the cell colonies had the
      potentiality of producing anti- alkaline phosphatase monoclonal antibody with
      high affinity. The complex from mAb and enzyme - for the third phase of APAAP
      technique - was very effective and its sensitivity was comparable to that of the
      similar foreign kit. CONCLUSION: Considering the high affinity of the mAb of the
      two hybridomas and the stability of the complex resulted from mixing mAb and the
      enzyme ALP for a long time, it is possible to use the obtained APAAP complex in
      the immunocyto (or histo) chemistry - as the third phase.

PMID- 18334747
TI  - Generation, characterization and biological activity of CCL2 (MCP-1/JE) and CCL12
      (MCP-5) specific antibodies.
AB  - The human CCL2 chemokine is implicated in many chronic inflammatory conditions.
      In the mouse, there are two CCL2 homologues, CCL2 (MCP-1/JE) and CCL12 (MCP-5).
      Both are potent monocyte chemoattractants and bind to and activate the same
      receptor, CCR2. The overlapping activities of these chemokines complicate the
      design of mouse model studies that are intended to mimic human disease. To study
      the roles of CCL2 and CCL12, we generated neutralizing antibodies specific to
      each chemokine. Consistent with binding and affinity analyses, the antibodies
      specifically inhibited CCL2- or CCL12- mediated Ca(2+) mobilization in THP-1
      cells. When tested in nude mice bearing human PANC-1 pancreatic tumor cells in
      Matrigel plugs, CCL2 and CCL12 antibodies potently inhibited tumor angiogenesis,
      indicating that both CCL2 and CCL12 may contribute to tumor angiogenesis.

PMID- 18334748
TI  - Generation and characterization of a therapeutic human antibody to melanoma
      antigen TYRP1.
AB  - TYRP1 (tyrosinase-related protein 1) is a melanoma antigen expressed in
      melanosomes and on the surface of melanoma cells. Previous studies have shown
      that mouse antibodies to TYRP1 localized to melanomas in vivo and inhibited tumor
      growth and metastasis. Here, we describe the characterization of a novel fully
      human anti-TYRP1 MAb (20D7) generated by immunizing HuMAb mice (Medarex). 20D7
      recognized recombinant and native human TYRP1 by Western blotting and ELISA, and
      native TYRP1 in melanoma cells as determined by flow cytometry analysis. 20D7
      cross-reacted with mouse TYRP1. The binding affinity to human TYRP1 for the human
      MAb was in the low nM range as determined by surface plasmon resonance kinetics.
      20D7 can bind to human and mouse Fc receptor and induce a strong ADCC response
      against human melanoma cells in vitro. The antitumor activity of 20D7 was tested
      in human melanoma xenografts and mouse metastatic melanoma models in athymic nude
      mice. Growth of s.c. human melanoma tumors and metastatic nodules of murine B16
      tumor were significantly suppressed by 20D7 compared to human IgG control. These
      results suggest that human anti-TYRP1 MAb may be a potent therapeutic for the
      treatment of malignant melanoma.

PMID- 18334749
TI  - Cumulative updating of approved biopharmaceuticals.
AB  - By definition, biopharmaceuticals includes the recombinant therapeutics proteins,
      monoclonal antibody and nucleic acid based-products used for medical purposes,
      which produce through the biotechnology. It has grown enormously during last 25
      years, even that each four pharmaceuticals product contains one biopharmaceutical
      product. This class of therapeutical generates in excess of $50 billion in sales
      annually. About 150 biopharmaceuticals have now received the medical approval.
      Actually, this white dimension is supported with strong R&D. The cost-estimated
      of total R&D per single biopharmaceutical approved molecule will reach $1318
      million. The majority of these materials are development and producing in
      mammalian cell line (70%), prokaryotic systems (15%), and yeast (5%),
      respectively. Few products are animal-derived, however the rest are completely
      from human-genes or humanized.

PMID- 18334750
TI  - Optimal seeding concentrations of hybridomas and other novel strategies to
      enhance antibody yield.

PMID- 18334751
TI  - Isolation and characterization of human antibodies targeting human aspartyl
      (asparaginyl) beta-hydroxylase.
AB  - Over-expression of the enzyme human aspartyl (asparaginyl) beta-hydroxylase
      (HAAH) has been detected in a variety of cancers. It is proposed that upon
      cellular transformation, HAAH is overexpressed and translocated to the tumor cell
      surface, rendering it a specific surface antigen for tumor cells. In this work,
      twelve human single-chain Fv fragments (scFv) against HAAH were isolated from a
      human non-immune scFv library displayed on the surface of yeast. Five of the
      twelve were reformatted as human IgG1. Two of the five IgGs, 6-22 and 6-23,
      showed significant binding to recombinant HAAH in ELISA, tumor cell lines, and
      tumor tissues. The apparent dissociation constants of 6-22 and 6-23 IgG were 1.0
      +/- 0.2 nM and 20 +/- 10 nM respectively. These two antibodies were shown to
      target different domains of HAAH, with 6-22 targeting the catalytic domain of
      HAAH and 6-23 targeting the N-terminal non-catalytic domain of HAAH. 6-22 IgG was
      further characterized, as it had high affinity and targeted the catalytic domain.
      6-22 IgG alone does not exhibit significant cytotoxicity toward the tumor cells.
      However, 6-22 internalizes into tumor cells and can therefore be employed to
      deliver cytotoxic moieties. A goat anti-human IgG-saporin conjugate was delivered
      into tumor cells by 6-22 IgG and hence elicited cytotoxicity toward the tumor
      cells in vitro. These tumor-binding human antibodies can potentially be used in
      both diagnosis and immunotherapy targeting HAAH-expressing tumor cells.

PMID- 18334753
TI  - Proteomic 2-D DIGE profiling of APP23 transgenic mice brain from pre-plaque and
      plaque phenotypes.
AB  - Alzheimer's disease is the most prevalent form of dementia associated with aging
      in the human population for which there is no biomarker for accurate and
      effective diagnosis at its early stage or monitoring of disease progression. In
      this study, we used 2-D DIGE to identify Alzheimer's disease-related proteins in
      the brains of APP23 mice used as a model for studying cerebral amyloidosis.
      Protein expression profiles in the brain of 2- and 24-month old female transgenic
      mice, displaying pre-plaque and plaque phenotypes, respectively, and 24-month old
      wild-type mice were compared to identify if changes at the protein level could be
      implicated in the early molecular events leading to cerebral amyloidosis. Seven
      such proteins were identified including kinesin heavy chain, dihydropyrimidinase
      related protein 2, beta-tubulin, two isomers of 3-phosphoglycerate dehydrogenase,
      ubiquinol cytochrome c reductase, and heat shock protein 84. The dysregulation of
      these proteins may have implications on pathways such as the mitochondrial
      respiratory chain, axonal transport, axon guidance, L-Serine biosynthesis and
      cytoskeletal reorganization, and thereby may represent events that precede and
      participate in the formation of senile plaque. Other detected protein changes
      were observed only in the plaque phenotype, and so are likely to be a consequence
      of plaque deposition and/or associated with neurodegenerative/repair processes.
      These proteins provide a basis for further dissecting the early mechanisms of
      Alzheimer's disease, and exploring their implications as relevant biomarker
      candidates of incipient Alzheimer's disease and progression in man.

PMID- 18334752
TI  - C-terminal cleavage of the amyloid-beta protein precursor at Asp664: a switch
      associated with Alzheimer's disease.
AB  - In addition to the proteolytic cleavages that give rise to amyloid-beta (Abeta),
      the amyloid-beta protein precursor (AbetaPP) is cleaved at Asp664
      intracytoplasmically. This cleavage releases a cytotoxic peptide, APP-C31,
      removes AbetaPP-interaction motifs required for signaling and internalization,
      and is required for the generation of AD-like deficits in a mouse model of the
      disease. Although we and others had previously shown that Asp664 cleavage of
      AbetaPP is increased in AD brains, the distribution of the Asp664-cleaved forms
      of AbetaPP in non-diseased and AD brains at different ages had not been
      determined. Confirming previous reports, we found that Asp664-cleaved forms of
      AbetaPP were increased in neuronal cytoplasm and nuclei in early-stage AD brains
      but were absent in age-matched, non-diseased control brains and in late-stage AD
      brains. Remarkably, however, Asp664-cleaved AbetaPP was prominent in neuronal
      somata and in processes in entorhinal cortex and hippocampus of non-diseased
      human brains at ages <45 years. Our observations suggest that Asp664 cleavage of
      AbetaPP may be part of the normal proteolytic processing of AbetaPP in young (<45
      years) human brain and that this cleavage is down-regulated with normal aging,
      but is aberrantly increased and altered in location in early AD.

PMID- 18334754
TI  - Nutritional biomarkers in Alzheimer's disease: the association between
      carotenoids, n-3 fatty acids, and dementia severity.
AB  - Carotenoids are fat-soluble antioxidants that may protect polyunsaturated fatty
      acids, such as n-3 fatty acids from oxidation, and are potentially important for
      Alzheimer's disease (AD) prevention and treatment. Fasting plasma carotenoids
      were measured in 36 AD subjects and 10 control subjects by HPLC. Correlations
      between plasma carotenoid levels, red blood cell (RBC) n-3 fatty acids, and
      dementia severity were examined in AD patients. Moderately severe AD patients
      (MMSE=16-19) had much lower plasma levels of two major carotenoids: lutein and
      beta-carotene, compared to mild AD patients (MMSE=24-27) or controls. Among AD
      patients, variables (lutein, beta-carotene, RBC docosahexaenoic acid (DHA) and
      LDL-cholesterol) were significantly correlated with MMSE. A lower MMSE score was
      associated with lower lutein, beta-carotene and RBC DHA levels, and a higher LDL
      cholesterol level. These variables explained the majority of variation in
      dementia severity (55% of variance in MMSE). Lutein, beta-carotene and beta
      cryptoxanthin were positively correlated with RBC DHA in AD patients. The
      association between higher carotenoids levels and DHA and higher MMSE scores,
      supports a protective role of both types of nutrients in AD. These findings
      suggest targeting multiple specific nutrients, lutein, beta-carotene, and DHA in
      strategies to slow the rate of cognitive decline.

PMID- 18334755
TI  - Is Alzheimer's disease a synaptic disorder?
AB  - BACKGROUND: In Alzheimer's disease (AD), the common symptom is loss of memory.
      Learning and memory are associated with amoeboid movements of synaptic endings.
      Docosahexaenoic acid (DHA) is a major lipid constituent of synaptic end sites.
      Minor changes in the fluidity of phospholipidic membranes have a dramatic impact
      on the function of synapses, where membrane fluidity may influence the
      neurotransmitter receptor activity. METHOD: Studies pertaining to the role of DHA
      as a neuroprotective agent was reviewed. RESULTS: Here we will show a conceptual
      framework for the role of DHA in the prevention of AD. The DHA content has been
      shown to be decreased in the brain and plasma of patients affected by AD. Aspirin
      triggers the generation of DHA-derived mediators that are themselves
      neuroprotective. CONCLUSION: Adequate dietary intakes of the neuroprotective DHA
      (and aspirin?) may slow down the progression of AD. An essential reserve of
      synapses from early development is needed.

PMID- 18334756
TI  - Increased levels of magnetic iron compounds in Alzheimer's disease.
AB  - A study of the magnetic properties of superior temporal gyrus brain tissue from
      11 Alzheimer's disease (AD) and 11 age-matched control subjects demonstrates an
      exponential correlation between the concentrations of the Fe;{2+}-ion-containing
      iron oxide, magnetite (Fe{3}O{4}), and the fraction of those particles that are
      smaller than 20 nm in diameter. These data provide circumstantial evidence in
      favor of their genesis within the 8 nm diameter cores of the iron storage protein
      ferritin. We also show, for the first time, that the total concentration of
      biogenic magnetite is generally higher in the AD brain (in some cases as much as
      15 times greater than controls) and that there are gender-based differences, with
      AD female subjects having significantly higher concentrations than all other
      groups. These results provide insights which may guide current efforts to develop
      iron-based MRI diagnosis of AD.

PMID- 18334757
TI  - Cognitive performance correlates with cortical isopeptide immunoreactivity as
      well as Alzheimer type pathology.
AB  - BACKGROUND: Protein cross-linking and aggregation are important molecular
      processes in Alzheimer's disease (AD), and tissue transglutaminase (tTG)
      catalyzes protein cross-linking. OBJECTIVES: To measure tTG, tTG enzyme activity
      and isopeptide, which is the product of tTG, in brain and to relate them to
      cognitive scores. METHODS: tTG and isopeptide levels were measured in frontal
      gray matter of 10 normal (NCI), 10 mild cognitive impairment (MCI) and 9 AD
      brains from the Religious Orders Study. tTG enzymatic activity was measured with
      a fluorescence assay. RESULTS: tTG protein and enzyme activity were highest in
      AD, but not significantly greater than MCI or NCI. In contrast, isopeptide
      immunoreactivity in formic acid extracts was significantly greater in AD than NCI
      and MCI. The level of insoluble formic acid extractable isopeptide correlated
      with several measures of cognitive function, including word generation and
      perceptual speed. Multiple linear regression analyses indicated that insoluble
      isopeptide immunoreactivity could be accounted for by a combination of factors in
      the formic acid extract, including Abeta, ubiquitin and tau. CONCLUSIONS:
      Accumulation of insoluble proteins with isopeptide bonds correlates with
      cognitive impairment. The relationship of isopeptide to other proteins that are
      also enriched in formic acid extracts suggests that several substrates of tTG may
      play a role in the pathogenesis of AD.

PMID- 18334758
TI  - S-adenosyl methionine: a natural therapeutic agent effective against multiple
      hallmarks and risk factors associated with Alzheimer's disease.
AB  - Recent preclinical and clinical findings demonstrate that dietary supplementation
      with S-adenosyl methionine alleviates a variety of risk factors and hallmarks
      associated with Alzheimer's disease. These findings support and extend prior
      studies, some of which are decades old, and support the notion that nutritional
      supplementation may represent an important augmentation for therapy in
      Alzheimer's disease.

PMID- 18334759
TI  - Co-localization and distribution of cerebral APP and SP1 and its relationship to
      amyloidogenesis.
AB  - Alzheimer's disease is characterized by amyloid-beta peptide (Abeta)-loaded
      plaques in the brain. Abeta is a cleavage fragment of amyloid-beta protein
      precursor (APP) and over production of APP may lead to amyloidogenesis. The
      regulatory region of the APP gene contains consensus sites recognized by the
      transcription factor, specificity protein 1 (SP1), which has been shown to be
      required for the regulation of APP and Abeta. To understand the role of SP1 in
      APP biogenesis, herein we have characterized the relative distribution and
      localization of SP1, APP, and Abeta in various brain regions of rodent and
      primate models using immunohistochemistry. We observed that overall distribution
      and cellular localization of SP1, APP, and Abeta are similar and neuronal in
      origin. Their distribution is abundant in various layers of neocortex, but
      restricted to the Purkinje cell layer of the cerebellum, and the pyramidal cell
      layer of hippocampus. These findings suggest that overproduction of Abeta in vivo
      may be associated with transcriptional pathways involving SP1 and the APP gene.

PMID- 18334760
TI  - Activation of the amyloidogenic route by NGF deprivation induces apoptotic death
      in PC12 cells.
AB  - Nerve growth factor (NGF) exerts a trophic, antiapoptotic action on several
      neuronal targets, including the clonal cell line PC12. In the current study, we
      demonstrate that withdrawal of this neurotrophin from PC12 differentiated cells
      causes overproduction of amyloid-beta (Abeta) peptides, which are the most toxic
      protein fragments directly implicated in the development of Alzheimer disease
      (AD), concomitantly with cell death by apoptosis. Abeta production and apoptotic
      death, occurring after withdrawal from NGF-differentiated PC12 cells, are
      completely inhibited by beta- and gamma-secretase inhibitors and by antibodies
      directed against Abeta peptides, favouring maintenance of PC12 morphology and
      neuritic network. These peptides are partially released and largely deposited as
      aggregates only soluble with strong detergent treatment generally employed to
      dissolve senile plaques. Furthermore, partial silencing of APP mRNA, by siRNA,
      reduces not only the extent of Abeta production but also apoptotic death. Abeta
      production and apoptosis are also induced in differentiated PC12 cells by kinase
      inhibitors of Trk-A, the high affinity receptor of NGF and, in this case, the co
      incubation with beta- and gamma-secretase inhibitors totally revert apoptosis.

PMID- 18334761
TI  - Memantine treatment in patients with mild to moderate Alzheimer's disease:
      results of a randomised, double-blind, placebo-controlled 6-month study.
AB  - Memantine is a moderate affinity, uncompetitive NMDA receptor antagonist
      currently approved for the treatment of moderate to severe Alzheimer's disease
      (AD). A 24-week, double-blind, placebo-controlled, study (Study 99679) conducted
      in Europe evaluated the efficacy and tolerability of 20 mg/day memantine in
      patients with mild to moderate AD. Patients were randomised to either memantine
      or placebo in a 2:1 ratio. Efficacy was primarily assessed as change from
      baseline in ADAS-cog and CIBIC-plus score. Of 470 patients randomised and treated
      (memantine, n=318; placebo, n=152), 85% and 91% completed the study. Memantine
      treated patients showed statistically significant improvement relative to placebo
      at weeks 12 and 18, and numerical superiority at week 24 on both efficacy scales.
      The lack of significance at week 24 was attributed to an unexpectedly high
      placebo response. Memantine was well tolerated with an adverse event profile
      similar to placebo. The data presented support the efficacy of memantine in mild
      to moderate AD.

PMID- 18334762
TI  - Publishing in the field of brain plasticity, repair and rehabilitation: an
      emerging neuroscience niche journal.
AB  - The journal Restorative Neurology and Neuroscience (RNN) is now published in its
      25th volume since its inception in 1989. RNN focuses on the emerging field of
      brain plasticity, repair and rehabilitation, including original and review papers
      both in basic research (animal experiments, in vitro studies) and in the clinical
      domain, including brain imaging studies. During the last decade RNN has
      experienced a steady progress in its reference value and scientific impact. The
      ISI-impact factor has risen from 1.117 (1997) to 2.862 (2006). This places the
      journal at the 81st rank among all 200 neuroscience journals, i.e. 60% of all
      neuroscience journals have a lower impact factor. When compared to other journals
      in the field of rehabilitation, RNN ranks number 1. Causes for this positive
      development are, among others: (1) the field of neuroplasticity, regeneration,
      recovery and rehabilitation is an emerging field in medicine and therefore the
      number of publications and their citation rate overall increases, (2) the special
      issues strategy, (3) a top level editorial board, and (4) the quality of papers
      submitted to RNN continuously improves as RNN is gaining increasing acceptance in
      the scientific community. Thus, in the space of neuroscience in general, and
      rehabilitation in particular, RNN has become a visible, high impact journal and a
      leading source of original scientific information pertaining to brain plasticity
      , rehabilitation and repair. RNN is likely to gain more momentum as the field
      matures further.

PMID- 18334763
TI  - Predicting improvement in the upper paretic limb after stroke: a longitudinal
      prospective study.
AB  - PURPOSE: A number of longitudinal studies show that about one third of all
      patients regain dexterity following a stroke. However, the determinants of
      improvement of upper limb function are largely unknown. The aim of the present
      study was to investigate the longitudinal relationship of functional change in
      the upper paretic limb and change in time-dependent covariates in order to
      develop a multivariable regression model to predict improvement in dexterity.
      METHODS: Based on 18 repeated measurements over time during the first post-stroke
      year, 101 stroke patients with first-ever ischemic middle cerebral artery strokes
      were investigated. Baseline characteristics as well as longitudinal information
      from Action Research Arm Test (ARAT), Fugl-Meyer arm and hand score (FM-arm and
      FM-hand), Motricity Index arm and leg score (MI-arm and MI-leg), letter
      cancellation task (LCT), Fugl-Meyer balance score (FM-balance) and progress of
      time were obtained prospectively. Outcome constituted of change scores on the
      ARAT over first year post stroke. Adjoining measurements of time-dependent
      variables were used to calculate time-dependent changes producing change scores.
      RESULTS: In total 1570 of the 1717 change scores were available for longitudinal
      regression analysis. The regression model shows that FM-hand change scores was
      the most important relative factor in predicting improvement on ARAT
      (standardized beta=0.357; p<0.001) followed by change scores on FM-arm
      (beta=0.007; p<0.001), whereas progress of time was significantly negatively
      associated with improvement on ARAT (beta=-0.001; p<0.001). CONCLUSIONS:
      Functional improvement of the upper paretic limb is mainly determined by
      improvement of the paretic hand, followed by synergistic independent movement of
      the paretic arm. Progress of time itself is an independent covariate that is
      negatively associated with upper limb function suggesting that most pronounced
      improvements occur earlier after stroke.

PMID- 18334764
TI  - Improvement of dexterity by single session low-frequency repetitive transcranial
      magnetic stimulation over the contralesional motor cortex in acute stroke: a
      double-blind placebo-controlled crossover trial.
AB  - PURPOSE: Increasing evidence suggests that the contralesional motor cortex (M1)
      inhibits the ipsilesional M1 in stroke patients. This inhibition could impair
      motor function of the affected hand. We investigated if inhibitory 1~Hz
      repetitive transcranial magnetic stimulation (rTMS) over the contralesional M1
      improved motor performance of the affected hand in acute stroke. METHODS: A
      double-blind study of real versus placebo rTMS was conducted. Twelve patients
      early after subcortical stroke (mean: 7 days) received 1200 stimuli of real and
      placebo rTMS in a crossover design. The sequence of stimulations was
      counterbalanced across subjects. Stimulus intensity was subthreshold (90% of
      motor threshold at rest). Motor function was tested by grip strength recordings
      and Nine Hole Peg Test (NHPT) executions before and after each rTMS session.
      RESULTS: Compared to sham stimulation, real rTMS improved NHPT results but not
      grip strength in the affected hand. No change of performance was observed for the
      unaffected hand. NHPT baseline repetitions in a subgroup of patients indicated
      stable motor performance prior to the rTMS sessions. CONCLUSIONS: The study
      suggests that therapeutic rTMS applications over the contralesional hemisphere
      are feasible in acute stroke patients and can transiently improve dexterity of
      the affected hand. RTMS may become an additional tool for early
      neurorehabilitation.

PMID- 18334765
TI  - Environmental enrichment improves functional and neuropathological indices
      following stroke in young and aged rats.
AB  - PURPOSE: Aging is associated with a temporally dysregulated cellular response to
      ischemia as well as poor functional recovery. While environmental enrichment has
      been shown to improve the behavioral outcome of stroke in young animals, the
      effect of an enriched environment on behavioral and neuropathological recovery in
      aged animals is not known. METHODS: Focal cerebral ischemia was produced by
      electrocoagulation of the right middle cerebral artery in 3 month- and 20 month
      old male Sprague-Dawley rats. The functional outcome was assessed in
      neurobehavioral tests conducted over a period of 28 days following surgery. Brain
      tissue was then immunostained for proliferating astrocytes and the infarct and
      scar tissue volumes were measured. RESULTS: Aged rats showed more severe
      behavioral impairments and diminished functional recovery compared to young rats.
      Most infarcted animals had disturbances of sensorimotor function, with recovery
      beginning later, progressing more slowly, and reaching a lower functional
      endpoint in aged animals. However, the enriched environment significantly
      improved the rate and extent of recovery in aged animals. Correlation analysis
      revealed that the beneficial effect of the enriched environment on recovery, both
      in young and aged rats, correlated highly with a reduction in infarct size, in
      the number of proliferating astrocytes, and in the volume of the glial scar.
      CONCLUSIONS: These results suggest that temporally modulating astrocytic
      proliferation and the ensuing scar formation might be a fruitful approach to
      improving functional recovery after stroke in aged rats.

PMID- 18334766
TI  - The novel substituted pyrimidine, KP544, reduces motor deficits in the R6/2
      transgenic mouse model of Huntington's disease.
AB  - PURPOSE: The purpose of this study was to test the potential therapeutic effects
      of the substituted pyrimidine, KP544, which has been shown to amplify the effects
      of nerve growth factor in vitro, on motor deficits in the R6/2 transgenic mouse
      model of Huntington's disease (HD). METHODS: Young, female R6/2 mice were given
      daily oral intubation of either 10 mg/kg KP544 or vehicle (0.5% methylcellulose)
      at 6 weeks of age and tested from postnatal weeks 8 through 12 on a battery of
      motor tasks, including assessments of clasping (drawing of the limbs to the torso
      when suspended by the tail), motor coordination on the rotarod, and spontaneous
      motor activity in the open-field. Following testing, the mice were sacrificed and
      the brains were sectioned and stained with cresyl violet for histological
      examination. RESULTS: KP544 treatment decreased balance deficits on the rotarod
      task, reduced clasping, delayed the onset of hypoactivity, and reduced
      enlargement of the lateral ventricles in R6/2 mice. CONCLUSION: These results
      suggest that KP544 can reduce motor deficits and anatomical alterations in R6/2
      mice. Further research into the use of KP544 as a potential pharmacotherapy HD is
      warranted.

PMID- 18334767
TI  - Five days versus a lifetime: intense associative vocabulary training generates
      lexically integrated words.
AB  - PURPOSE: The best predictor of successful language therapy in both the acute and
      chronic stages after stroke is the treatment intensity, i.e., number of hours
      trained per week. Associative learning should be particularly suited for intense
      training because it places low demands on (executive) cognitive functions. It is
      as of yet unresolved, however, whether associative training is a valid language
      learning approach. It could merely produce superficial associations of acoustic
      visual information, which remain outside lexical and conceptual networks.
      METHODS: We here examined if five days of associative training in a miniature
      vocabulary are sufficient for an integration of novel words into the learner's
      mental lexicon. Twelve healthy subjects were trained 20 min daily for five
      consecutive days simply by frequent couplings of object pictures with novel
      words. RESULTS: Correct responses for couplings of novel words and object names
      increased from a chance level of 50 percent on day 1 to >90 percent accuracy on
      day 5. Prior to and immediately after the vocabulary training, a cross-modal
      semantic priming test was administered to determine the degree of lexical
      integration of the novel words into the language system already in situ.
      CONCLUSIONS: Results show that learned novel words had acquired semantic
      characteristics, which were comparable to words of subjects' native language
      acquired over a lifetime. Thus, comprehensive integration of the novel words into
      existing conceptual and lexical networks occurred after just five days of
      training. This lays the foundation for probing associative training approaches in
      aphasia therapy, with the hope of increasing therapy efficiency.

PMID- 18334768
TI  - Mental practice improves hand function after hemiparetic stroke.
AB  - PURPOSE: In a multiple baseline design, we tested the hypothesis that imagery of
      finger movements is a specific strategy to improve hand function. METHODS: The
      effect of mental training of sequential finger movements (n=6) on hand function
      was compared to the repetitive execution of the same movements (n=6) and
      conventional physical therapy (n=5) in 17 patients after their first hemiparetic
      stroke. The behavioral outcome measures consisted of peak force of the pinch grip
      using a force transducer and manipulation functions of the upper extremity
      (Jebsen-test). In addition, activities of daily living (Barthel Index) were
      acquired to describe the population. RESULTS: Mental training resulted in an
      increase in the peak force of the pinch grip and generalized in a better
      functionality of the upper extremity (Jebsen-test). This effect was similar to
      the repetitive execution of the movements and superior to conventional
      physiotherapy. CONCLUSIONS: Our results suggest that the control of finger
      movements benefits from mental training of sequential finger movements and, thus,
      may be employed as a strategy in post-stroke rehabilitation.

PMID- 18334769
TI  - Early pubertal female rats are more resistant than males to 6-hydroxydopamine
      neurotoxicity and behavioural deficits: a possible role for trophic factors.
AB  - PURPOSE: The infusion of 6-hydroxydopamine (6-OHDA) into the nigrostriatal
      pathway in rats is commonly used to produce an animal model of Parkinson's
      disease (PD). However, most studies use male adult animals only. The present
      study focused on possible gender differences in vulnerability to 6-OHDA during
      the early pubertal period when the effects exerted by gonadal steroid hormones
      are unpronounced. METHODS: Young Sprague-Dawley rats, 35 days of age, were given
      a low vs. a higher dose of 6-OHDA in the medial forebrain bundle (MFB). Control
      rats received equivalent saline infusions. At 14 days post-surgery the rats were
      evaluated for forelimb akinesia. RESULTS: For the higher dose of 6-OHDA the
      female rats were less impaired than males in making adjustment steps in response
      to a weight shift and in a vibrissae-evoked forelimb placing test. Tyrosine
      hydroxylase (TH) immunoreactivity was significantly higher for the female rats.
      CONCLUSION: Early gender differences in cell survival factors and/or other
      promoters of neuroplasticity may have contributed to the beneficial outcome in
      the females. For example, NGF was found to be higher in the female rats following
      administration of DA neurotoxin. It is unclear whether gonadal steroids are
      involved, and if so, whether female hormones are protective or whether male
      hormones are prodegenerative. Determining the mechanisms for the improved outcome
      in the young female rats may lead to potential treatment strategies in PD.

PMID- 18334770
TI  - Supraspinal inputs reduce corticomotor excitability during passive movement:
      evidence from a pure sensory stroke.
AB  - Corticomotor excitability is reduced during rhythmic passive movement compared to
      rest, but it is not known whether the mechanism is purely segmental or includes a
      supraspinal pathway. To determine how interruption of sensory projections at a
      supraspinal level affects corticomotor excitability during passive movement, we
      measured the amplitude of motor evoked potential (MEP) during 1 Hz cyclic index
      finger movements in a patient with a brainstem and thalamus lesion that resulted
      in a pure sensory stroke. Measurements of MEP amplitude and proprioception were
      made 14 and 64 days post-stroke. In the first study, when subjective position
      sense was reduced for the index finger, MEP amplitude was significantly increased
      during passive movement compared to rest (4.6+/-0.2 SEM mV vs. 4.0+/-0.2 mV;
      p=0.0281). However in the second study, when position sense had returned to
      normal, MEP amplitude was significantly reduced during movement compared to rest
      (6.2+/-0.3 mV vs. 6.6+/-0.1 mV; p=0.0224). These observations provide evidence
      that supraspinal sensory pathways are involved in reducing corticomotor
      excitability during rhythmic passive movement.

PMID- 18334771
TI  - Axonal rearrangement without reexpression of a growth associated marker: evidence
      from the compression of the retinotectal system in adult goldfish.
AB  - PURPOSE: Growing axons express a number of proteins associated with axonal growth
      which are thought to be critical for regeneration and sprouting. Whether these
      proteins are expressed during injury-induced axonal remodeling is tested in this
      paper. METHODS: The posterior half of the adult goldfish tectum was removed
      leaving the anterior half intact. This causes optic fibers from nasal retina,
      which project to posterior tectum, to displace temporal fibers from the anterior
      remnant and form a compressed retinotopic projection of the entire retina onto
      the anterior tectum. Immunohistochemistry using an antibody shown here to
      recognize growing and regenerating fibers in goldfish was used to monitor optic
      fibers. RESULTS: As expected, surgery induced reactivity in the axotomized nasal
      axons peaking at 1 month which returned to normal at 2 months when compression
      was completed. Unexpectedly, axons from temporal retina showed no detectable
      reactivity even though they were induced to grow anteriorly by the invading nasal
      fibers. CONCLUSIONS: Extensive axonal remodeling and synaptic rearrangement can
      occur without reentering the growth state associated with axonal growth and
      regeneration.

PMID- 18334772
TI  - The Excite Trial: relationship of intensity of constraint induced movement
      therapy to improvement in the wolf motor function test.
AB  - PURPOSE: To examine the relationship between change scores on the log mean Wolf
      Motor Function Test (lmWMFT) and the intensity of supervised Constraint Induced
      Movement Therapy (CIMT) in participants with subacute and chronic stroke.
      METHODS: A retrospective analysis of data from 169 EXCITE participants who
      received CIMT either immediately after randomization or one year later was
      undertaken. During waking hours, participants wore a restraining mitt on the less
      affected extremity. The lmWMFT was administered before and after the two week
      treatment block. RESULTS: Significant relationships were seen between the
      intensity of training and functional score in the immediate, lower functional
      group for whom more training in adaptive task practice resulted in poorer
      outcomes (p=0.01) and in the immediate, higher functioning group for whom more
      training in repetitive task practice resulted in poorer outcomes (p=0.02). Female
      participants in the immediate group showed less progress in lmWMFT scores with
      greater amounts of total training (p=0.01). Functional level, gender, and
      concordance did not modify any other relationship. Both higher functioning
      participants who trained within the normal ratio (N=50) and who were exposed to
      more than the prescribed adaptive task practice (N=11) experienced a significant
      improvement in the lmWMFT score (p=0.03 and p=0.02, respectively) compared to
      those higher functioning participants who experienced excessive repetitive task
      practice. CONCLUSION: Applying CIMT to a large sample of participants with stroke
      resulted in directionally inappropriate but significant relationships between
      intensity and lmWMFT scores in the immediate but not the delayed group. Our data
      also suggest that functional improvements observed in the EXCITE Trial might be
      attributable to training components other than the designated ratio of training
      approaches (adaptive and repetitive task practice).

PMID- 18334773
TI  - Recovery of visual field defects: a large clinical observational study using
      vision restoration therapy.
AB  - PURPOSE: In small experimental trials, vision restoration therapy (VRT), a home
      based rehabilitation method, has shown to enlarge the visual field and improve
      reaction times in patients with lesion involving the CNS. We now evaluated the
      outcome of VRT in a large sample of clinical patients and studied factors
      contributing to subjective and objective measures of visual field alterations.
      METHODS: Clinical observational analysis of visual fields of 302 patients before
      and after being treated with computer-based vision restoration therapy for a
      period of 6 months at eight clinical centers in central Europe. The visual field
      defects were due to ischemia, hemorrhage, head trauma, tumor removal or anterior
      ischemic optic neuropathy. Primary outcome measure was a visual field assessment
      with super-threshold perimetry. Additionally, conventional near-threshold
      perimetry, eye movements and subjective reports of daily life activities were
      assessed in a subset of the patients. RESULTS: VRT improved patients' ability to
      detect super-threshold stimuli in the previously deficient area of the visual
      field by 17.2% and these detection gains were not significantly correlated with
      eye movements. Notable improvements were seen in 70.9% of the patients. Efficacy
      was independent of lesion age and etiology, but patients with larger areas of
      residual vision at baseline and patients>65 years old benefited most.
      Conventional perimetry validated visual field enlargements and patient
      testimonials confirmed the improvement in every day visual functions.
      CONCLUSIONS: VRT improves visual functions in a large clinical sample of patients
      with visual field defects involving the CNS, confirming former experimental
      studies.

PMID- 18334774
TI  - Effects of single versus combinatorial treatment strategies on beta II-tubulin
      gene expression in axotomized hamster rubrospinal motoneurons.
AB  - PURPOSE: betaII-tubulin, a regeneration-associated gene, is upregulated in
      injured peripheral neurons, but significantly less so in injured central neurons.
      Using a hamster dorsal spinal cord injury (SCI), the ability of single versus
      combinatorial treatment strategies to alter betaII-tubulin mRNA expression in
      rubrospinal motoneurons (RSMN) was examined. We have shown that systemic
      testosterone propionate (TP) treatment in combination with peripheral nerve
      grafting into a SCI site produces a peripheral-like pattern of betaII-tubulin
      mRNA expression in injured RSMN. In the present study, selected single- and
      combinatorial-therapy strategies were tested for their ability to promote a
      sustained upregulation of betaII-tubulin mRNA levels in injured RSMN. METHODS:
      Single treatments of olfactory ensheathing cells (OEC), brain-derived
      neurotrophic factor (BDNF), or Schwann cells (SC) vs combinatorial treatments
      (SC+TP, OEC+TP, and OEC+BDNF) were administered to hamsters following a dorsal
      SCI. Quantitative in situ hybridization in conjunction with a betaII-tubulin cDNA
      probe was accomplished. RESULTS: All of the single-therapy treatments tested were
      able to prevent the downregulation of betaII-tubulin mRNA that occurred a week
      after injury alone, but only BDNF maintained high levels of betaII-tubulin mRNA.
      In contrast, all combinatorial treatments tested maintained the upregulation of
      betaII-tubulin mRNA expression in injured RSMN 1 week post-SCI. CONCLUSIONS:
      Targeting both intrinsic and extrinsic components of CNS injury can re-program
      elements of the molecular response of injured central motoneurons.

PMID- 18334775
TI  - Electrical stimulation prior to delayed reinnervation does not enhance recovery
      in muscles of rats.
AB  - PURPOSE: Prolonged denervation of skeletal muscles results in atrophy and poor
      recovery of motor function following delayed reinnervation. Electrical
      stimulation reduces denervation atrophy. We hypothesized that electrical
      stimulation of denervated extensor digitorum longus (EDL) muscles during a
      prolonged period between nerve axotomy and opportunity for reinnervation by
      motoneurons after nerve-repair would enhance the recovery of muscle mass, force
      and motor-function. METHODS: The EDL muscles of rats were denervated for 3.5
      months by peroneal nerve axotomy, then repaired with an end-to-end neurorrhaphy,
      and allowed to recover for 6.5 months. During the period of denervation, some of
      the rats received a protocol of electrical stimulation that had previously been
      shown to dramatically attenuate the effects of denervation atrophy through 4
      months. Other experimental groups included unoperated control muscles, denervated
      muscles, and axotomy followed immediately by nerve-repair. Final evaluations
      included walking track analysis, maximum force measured in situ by indirect
      stimulation of the nerve, and muscle mass. RESULTS: The hypothesis was not
      supported. Electrical stimulation during the period of denervation did not
      enhance recovery of muscle mass, force or motor function. CONCLUSION: The primary
      factors that inhibited reinnervation and recovery following delayed reinnervation
      were not alleviated by the electrical stimulation during the period of muscle
      denervation.

PMID- 18334776
TI  - Plasma viscosity, an early cardiovascular risk factor in women with subclinical
      hypothyroidism.
AB  - OBJECTIVE: It is controversial, if subclinical hypothyroidism increases
      cardiovascular risk. Plasma viscosity is a hemorheological parameter, which is
      accepted as an early cardiovascular risk factor. We investigated the alterations
      in plasma viscosity in women with subclinical hypothyroidism. DESIGN: 40 female
      patients with subclinical hypothyroidism and 31 age- and weight-matched healthy
      women were included. Free thyroxine (FT4), thyroid stimulating hormone (TSH),
      lipid parameters, fibrinogen, C-reactive protein (CRP) levels, hematocrit and
      plasma viscosity were measured in all subjects. MAIN OUTCOME: Plasma viscosity,
      total cholesterol and low density lipoprotein were significantly increased and
      high density lipoprotein was significantly decreased in patients with subclinical
      hypothyroidism. No significant correlation was found among the parameters.
      CONCLUSION: Increased plasma viscosity in patients' group suggests that
      cardiovascular risk might be increased in patients with subclinical
      hypothyroidism. As far as we could reach, this is the first study concerning
      plasma viscosity in subclinical hypothyroidism.

PMID- 18334777
TI  - Role of plasma viscosity and plasma homocysteine level on hyperinsulinemic obese
      female subjects.
AB  - Obesity is associated with atherosclerotic risk factors, including reduced blood
      flow, endothelial dysfunction, lipid disorders and hyperinsulinemia. In recent
      years, several studies have demonstrated that elevated homocysteine is a risk
      factor for atherosclerosis. This study was aimed at determining whether any
      relationship between plasma viscosity and homocysteine levels in patients with
      normo and hyperinsulinemic obese patients. Obese women (n=75) and healthy, age
      matched non-obese women (n=70) was included in our study. Plasma viscosity, tHcy,
      insulin level, total-C, LDL-C, HDL-C, triglyceride and glucose level were
      significantly higher in obese subjects than in non-obese subjects. Obese subjects
      were also divided into two groups, according to the basal insulin levels as normo
      and hyper insulinemic. Hyperinsulinemic obese subjects had significantly higher
      PV level compared with normoinsulinemic subjects. When correlation analyses were
      performed normoinsulinemic obese subjects, significant correlations were found
      between PV and total-C (r: 0.776) and insulin level (r: 0.752), BMI (r: 0.580),
      HOMA-IR (r: 0.510). PV was positively correlated with total-C (r: 0.485), insulin
      level (r: 0.624), BMI (r: 0.624) and HOMA-IR ratio (r: 0.707), in
      hyperinsulinemic obese subjects. Hcy was positively correlated BMI in both
      groups. In conclusion that, it is point out that elevated homocysteine and
      increased PV are two factors that may act separately and probably do not affect
      each other.

PMID- 18334778
TI  - Preventive effects of genistein on leukocyte adhesion in femur venules and on
      bone-loss induced in ovariectomized female rats.
AB  - This study was aimed to examine effects of genistein on leukocyte adhesion in
      femur microcirculation in relation to bone-loss induced in ovariectomized female
      rats. Sixty-four female Wistar rats were divided into 4 groups: sham (daily
      treated with vehicle; DMSO, sc; 100 microl/day), ovariectomized rat treated with
      vehicle (OVX(veh)), 17beta-estradiol treated-ovariectomized rat (OVX(E2), 5
      microg/kg/day, s.c.) and genistein treated-ovariectomized rat (0.25 mg/kg/day,
      s.c.; OVX(gen)). One and three weeks after the ovariectomy, blood flow perfusion
      (BF) in femur tissue was measured using laser Doppler flowmetry. Leukocyte
      adhesion in femur venules (15-30 microm in diameter) of each group was evaluated
      by intravital fluorescence videomicroscopy. The bone mineral content (BMC) was
      measured and expressed in terms of ratio of ash-to-dry matter weight. Serum
      osteocalcin and alkaline phosphatase levels were determined using
      chemiluminescence immunoassay. In both one and three week-OVX(veh), leukocyte
      adhesion increased significantly, compared to their age-matched sham groups, but
      it decreased significantly in OVX(gen), compared to OVX(veh) (p<0.05). In three
      week-OVX(gen), both BF and BMC increased significantly, but osteocalcin and
      alkaline phosphatase levels decreased, compared to those of three week-OVX(veh).
      In conclusion, genistein supplementation could effectively prevent bone-loss and
      microvascular endothelial dysfunction induced by estrogen deficiency.

PMID- 18334779
TI  - Flow-dependent accumulation of LDL in co-cultures of endothelial and smooth
      muscle cells in the presence of filtration flow through the cell layer.
AB  - To elucidate the roles of blood flow and transmural filtration flow in localized
      LDL accumulation in vascular walls, we studied the effects of flow velocity on
      LDL concentration at the cell surface and LDL uptake by co-cultures of vascular
      endothelial cells (ECs) and smooth muscle cells using a parallel-plate flow cell
      with or without filtration flow. Co-cultures were prepared on porous membranes.
      In the presence of filtration flow through the cell layer, the LDL concentration
      at the cell surface increased when the perfusion velocity was decreased (shear
      stress was decreased from 1.5 to 0.2 Pa). In the absence of filtration flow, LDL
      concentration remained unchanged despite changes in flow velocity. LDL uptake by
      the cells was proportional to its surface concentration that varied inversely
      with flow velocity. Therefore, in the presence of filtration flow, LDL
      accumulation was greater under conditions of low shear stress (0.2 Pa) than with
      high shear stress (1.5 Pa). In contrast, in the absence of filtration flow, LDL
      uptake was almost proportional to the magnitude of shear stress. These results
      suggest that shear stress-induced biological responses of ECs and transmural
      filtration flow, both play important roles in localized LDL accumulation in
      vascular walls.

PMID- 18334780
TI  - Hemorheology and heart rate variability: is there a relationship?
AB  - The aim of the present study was to test the relationships between hemorheology
      and autonomic nervous system (ANS) activity in 23 sickle cell trait (SCT)
      carriers and 17 control subjects. Hemorheological parameters were assessed at
      rest. Nocturnal ANS activity was calculated from heart rate variability indices.
      Impairment was observed in both domains in SCT carriers as they showed higher
      blood viscosity, higher red blood cell rigidity and a lower index of oxygen
      supply to tissues, as well as lower ANS activity. The index of oxygen supply to
      tissues was positively correlated with some of the indices of parasympathetic
      activity and global ANS activity. Negative correlations were found between blood
      viscosity and the very low frequency of the spectrum (VLF) that contains partial
      parasympathetic activity and between red blood cell rigidity and the percentage
      of differences between adjacent normal RR intervals more than 50 ms (PNN50),
      which also describes parasympathetic activity. These results support the
      hypothesis that autonomic nervous system equilibrium is affected by perturbations
      in blood rheology. Mechanisms have yet to be elucidated.

PMID- 18334781
TI  - Studies of whole blood coagulation by oscillatory shear, thromboelastography and
      free oscillation rheometry.
AB  - We report studies of the coagulation of samples of whole human blood by
      oscillatory shear techniques, including Fourier Transform Mechanical Spectroscopy
      (FTMS). These techniques are used herein to identify the Gel Point of coagulating
      blood in terms of the Chambon-Winter Gel Point criterion which provides a
      rheometrical basis for detecting the establishment of an incipient clot. A
      comparison of the results of FTMS with those obtained from measurements involving
      a Thromboelastograph (TEG) and a Free Oscillation Rheometer (FOR) indicate that
      the latter techniques are not capable of detecting the incipient clot, whose
      establishment occurs several minutes prior to TEG or FOR-based assessments of
      clot formation time. The results of the present study suggest that FTMS is a
      useful tool in blood clotting research, being capable of providing a global
      coagulation profile in addition to detecting the instant of incipient clot
      formation.

PMID- 18334782
TI  - Changes in acral blood flux under local application of ropivacaine and lidocaine
      with and without an adrenaline additive: a double-blind, randomized, placebo
      controlled study.
AB  - Vascular effects of local anesthetics are especially important in dermatological
      surgery. In particular, adequate perfusion must be ensured in order to offset
      surgical manipulations during surgical interventions at the acra. However, the
      use of adrenaline additives appears fraught with problems when anesthesia affects
      the terminal vascular system, particularly during interventions at the fingers,
      toes, penis, outer ears, and tip of the nose. We studied skin blood flux at the
      fingerpads via laser Doppler flowmetry over the course of 24 hours in a
      prospective, double-blind, randomized, placebo-controlled study with 20
      vascularly healthy test persons following Oberst's-method anesthetic blocks. In
      each case, 6 ml ropivacaine (7.5 mg/ml) (A), lidocaine 1% without an additive
      (B), and lidocaine 1% with an adrenaline additive (1:200,000) (C) was used
      respectively as a verum. Isotonic saline solution was injected as a placebo (D).
      Measurements were carried out with the aid of a computer simultaneously at D II
      and D IV on both hands. Administration of (A) led to increased blood flux
      (+155.2%); of (B) initially to a decrease of 27%; of (C) to a reduction of 55%
      which was reversible after 40 minutes and of (D) to no change.(A) resulted in
      sustained vasodilatation which was still demonstrable after 24 h. (B) had notably
      less vasodilative effect, although comparison with (D) clearly showed that (B) is
      indeed vasodilative. (C) resulted in only a passing decrease in perfusion; this
      was no longer measurable when checked after 6 and 24 h. This transient inadequacy
      of blood flux also appeared after administration of (D). These tests show that
      adrenaline additive in local anesthesia does not decrease blood flow more than
      55% for a period of 16 min. Following these results an adrenaline additive can be
      safely used for anesthetic blocks at the acra in healthy persons.

PMID- 18334783
TI  - AUTOPILOT-BT: a system for knowledge and model based mechanical ventilation.
AB  - A closed-loop system (AUTOPILOT-BT) for the control of mechanical ventilation was
      designed to: 1) autonomously achieve goals specified by the clinician, 2)
      optimize the ventilator settings with respect to the underlying disease and 3)
      automatically adapt to the individual properties and specific disease status of
      the patient. The current realization focuses on arterial oxygen saturation
      (SpO(2)), end-tidal CO(2) pressure (P(et)CO(2)), and positive end-expiratory
      pressure (PEEP) maximizing respiratory system compliance (C(rs)). The "AUTOPILOT
      BT" incorporates two different knowledge sources: a fuzzy logic control
      reflecting expert knowledge and a mathematical model based system that provides
      individualized patient specific information. A first evaluation test with respect
      to desired end-tidal-CO(2)-level was accomplished using an experimental setup to
      simulate three different metabolic CO(2) production rates by means of a physical
      lung simulator. The outcome of ventilator settings made by the "AUTOPILOT-BT"
      system was compared to those produced by clinicians. The model based control
      system proved to be superior to the clinicians as well as to a pure fuzzy logic
      based control with respect to precision and required settling time into the
      optimal ventilation state.

PMID- 18334784
TI  - Interference of neodymium magnets with cardiac pacemakers and implantable
      cardioverter-defibrillators: an in vitro study.
AB  - Permanent magnets may interfere with the function of cardiac pacemakers and
      implantable cardioverter-defibrillators (ICDs). Neodymium-iron-boron (NdFeB)
      magnets have become widely available in recent years and are incorporated in
      various articles of daily life. We conducted an in-vitro study to evaluate the
      ability of NdFeB magnets for home and office use to cause interference with
      cardiac pacemakers and ICDs. The magnetic fields of ten NdFeB magnets of
      different size and shape were measured at increasing distances beginning from the
      surface until a field-strength (B-field) value of 0.5 mT was reached.
      Furthermore, for each magnet the distance was determined at which a sample
      pacemaker switched from magnet mode to normal mode. Depending on the size and
      remanence of individual magnets, a B-field value of 0.5 mT was found at distances
      ranging from 1.5 cm to 30 cm and a value of 1 mT at distances from 1 cm to 22 cm.
      The pacemaker behavior was influenced at distances from 1 cm to 24 cm. NdFeB
      magnets for home and office use may cause interference with cardiac pacemakers
      and ICDs at distances up to 24 centimeters. Patient education and product
      declarations should include information about the risk associated with these
      magnets.

PMID- 18334785
TI  - Configuration of anchorage holes affects cemented fixation of the acetabular
      component in total hip replacement: an in vitro study.
AB  - Although surgical fixation techniques are major contributing factors to the
      survivorship of total hip replacements, they vary considerably among orthopaedic
      surgeons. We investigated the effect of the following configuration of anchorage
      holes on the stability of acetabular component fixation: 3 x 12 mm, 3 x 6 mm, 6 x
      6 mm, and 12 x 6 mm. The reconstructed acetabulae were tested to torque failure,
      whilst being subjected to a compressive load of 2.1 KN. Higher torque to failure
      values were obtained for specimens with three 12 mm anchorage holes, compared
      with six or more 6 mm anchorage holes and were in line with our computer
      simulation results. We propose that the longevity of cemented total hip
      replacements could be improved by drilling a few large anchorage holes.

PMID- 18334786
TI  - A spheroidal control volume for the quantitative measurement of regurgitant flow
      by cardiac MRI.
AB  - PURPOSE: We sought to show that a spheroidally shaped control volume (CV), formed
      from a minimal MRI data set, can be used to measure regurgitant flow through a
      defective cardiac valve consistently and accurately under a variety of flow
      conditions. MATERIALS AND METHODS: Using a pulsatile flow pump and phantoms
      simulating severe valvular regurgitation, we acquired 31 scans of two or three
      radially oriented slices, using a variety of flow waveforms and regurgitant
      volumes of 12 to 55 ml. Data sets included high- and low-resolution scans, and
      variable-rate sparse sampling was also applied to reduce the scan time. An oblate
      spheroid was placed in the pump chamber opposite the jet and fit as tightly as
      possible to isomagnitude velocity contours at 25% of the velocity encoding limit.
      RESULTS: Normalized regurgitant volumes (NRVs) expressed as a percentage of the
      pump setting were obtained from the product of the spheroid surface area with the
      velocities normal to it. Mean +/- SD NRV values were 96.8 +/- 6.6% for all scans.
      Imaging times in the breath-hold range were obtained using reduced resolution and
      variable-rate sparse sampling approaches without significant degradation in
      accuracy. CONCLUSION: In our preliminary findings, the spheroidal CV method
      showed clear potential for the development of a robust, clinically feasible
      technique for the measurement of regurgitant volume.

PMID- 18334787
TI  - Tissue-level failure accumulation in vertebral cancellous bone: a theoretical
      model.
AB  - Vertebral compression fractures are a potentially severe injury, which is
      characteristic to osteoporotic elderly. Despite being a significant healthcare
      problem, the etiology of compression fractures is not fully understood, and there
      are no biomechanical models in the literature that describe the development of
      these fractures based on cancellous bone failure accumulation. The objective of
      this study was therefore to develop a computational model of tissue-level failure
      accumulation in vertebral cancellous bone, which eventually leads to compression
      fractures. The model predicts the accumulated percentage of broken trabeculae
      delta in a vertebral region of interest (ROI) over 60 years, by employing Euler's
      theory for elastic buckling. The accumulated failure delta is calculated as
      function of the daily activity characteristics and rate of annual bone loss
      (RABL) with aging. An RABL of unity represents the normal bone loss attributed to
      aging per se, whereas RABL>1 is assumed to represent pathological bone metabolism
      such as osteoporosis. Simulations were conducted for a range of RABLs, to
      determine the effect of changes in bone metabolism on the accumulation of bone
      failure. Results showed that bone failure rapidly increased with RABL. Generally,
      trabecular failure was shown to become more severe for RABL>4. Total failure was
      exhibited at RABL=7.5 for the central ROI, and at RABL=8.5 for the sub-endplate
      ROI. We concluded that vertebral compression fractures advance monotonically
      between the age of 50-55 years and 70 years, and may accelerate thereafter if
      RABL is high (~8). Additionally, the model identified weight lifting as the
      action that most dramatically accelerated the destruction of osteoporotic spinal
      cancellous bone. The present biomechanical model is useful for understanding the
      etiology of compression fractures, and potentially, depending on further
      experimental characterization of RABL, for considering the effects of medications
      that influence bone metabolism on patient prognosis.

PMID- 18334788
TI  - Analysis of mechanical interaction between human gluteal soft tissue and body
      supports.
AB  - Pressure sores are the most common complication associated with patient
      immobilization. They develop through sustained localized tissue strain and
      stress, primarily caused by body supports. Modifying support design can reduce
      the risk and extent of pressure sore development with computational simulations
      helping to provide insight into tissue stress-strain distribution. Appropriate
      material parameters for human soft tissue and support material, as well as
      precise anatomical modelling, are indispensable in this process. A finite element
      (FE) model of the human gluteal region based on magnetic resonance imaging (MRI)
      data has been developed. In vivo human gluteal skin/fat and muscle long-term
      material parameters as well as open-cell polyurethane foam support long-term
      material parameters have been characterised. The Ogden form for slightly
      compressible materials was employed to describe human gluteal soft tissue
      behaviour. Altering support geometries and support materials, effects on human
      gluteal soft tissue could be quantified. FE-analysis indicated maximal tissue
      stress at the muscle-bone interface, not at the skin. Shear strain maxima were
      found in the muscle layer near the fat-muscle interface. Maximum compressive
      stress magnitude at the sacral bone depended strongly on the behaviour of the
      pelvic diaphragm musculature. We hypothesize that the compliance of the muscles
      forming the pelvic diaphragm govern the relative motion of the buttock tissue to
      the adjacent bone structure under compression, thus influencing tissue stress
      magnitudes.

PMID- 18334789
TI  - Trends in human birth weight across two successive generations.
AB  - OBJECTIVE: To determine the correlation between parental and offspring
      birthweight (BW) in India. METHODS: The study involved two birth cohorts of
      successive generations. The parental cohort comprised of 472 fathers and 422
      mothers from an earlier study. Details of their anthropometry at birth and in
      adulthood were available. 1525 children born to them comprised the offspring
      cohort. BW was obtained from hospital records for the offspring cohort. Odds
      ratios and regression coefficients were calculated to estimate the risks of a low
      birth weight (LBW) parent producing a LBW baby and quantitate the effects after
      adjusting for confounders. RESULTS: A LBW mother had a 2.8 times risk (95%CI 1.2
      6.4) of delivering a LBW baby (p=0.02) and a LBW father was twice as likely to
      produce a LBW baby (OR 2.2; 95%CI 1.0 - 4.8; p=0.05). Every 100g increase in
      maternal BW was associated with an increase in offspring BW of 14 g; the
      equivalent figure for paternal BW was 18.1g (p< 0.001 for both). Between the
      generations, the incidence of LBW decreased from 19.7% to 17.2% (p=0.1). Mean BW
      increased in males (2846 g vs 2861 g; p=0.59) but not in females (2790 g vs 2743
      g; p=0.08). CONCLUSION: Both maternal and paternal BW are strong determinants of
      offspring BW. The effect of mothers' BW on offspring BW is weaker than that seen
      in developed nations. Stronger intrauterine constraint exhibited by Indian women
      secondary to a higher prevalence of growth restriction in utero may be
      responsible. Paternal effects may be governed by paternal genes inherited by the
      offspring.

PMID- 18334790
TI  - Transcutaneous bilirubin in predicting hyperbilirubinemia in term neonates.
AB  - OBJECTIVE: To assess the utility of 24 and 48 hours transcutaneous bilirubin
      (TcB) index for predicting subsequent significant hyperbilirubinemia in healthy
      term neonates. METHODS: TcB indices were obtained for healthy, breastfed, term
      AGA newborns at 24 +/- 2, 48 +/- 2 and subsequently at intervals of 24 hours.
      Neonates with illness, on treatment and positive Direct Coomb's test were
      excluded. Serum bilirubin levels were obtained whenever indicated. Neonates
      having serum bilirubin > or = 17 mg/dL were considered as significant
      hyperbilirubinemia. The 24 and 48 hour TcB indices, as risk predictors for such
      hyperbilirubinemia were determined. RESULTS: Study included 461 healthy term
      neonates. The mean birth weight was 2949 (+/- 390) gm and mean gestation of 38.6
      (+/- 1.1) weeks. Eight one (17.6%) had significant hyperbilirubinemia. Of 461,
      135 (29.3%) had TcB index. CONCLUSION: The 24 and 48 hour TcB indices are
      predictive for subsequent significant hyperbilirubinemia and can guide clinician
      in early discharge of healthy term newborns.

PMID- 18334791
TI  - Problems related to menstruation amongst adolescent girls.
AB  - OBJECTIVE: To study the types and frequency of problems related to menstruation
      in adolescent girls and the effect of these problems on daily routine. METHODS:
      Girls in the age group 13-19 years who had had menarche for at least one year at
      the time of study. 198 adolescent girls have been studied. Data was collected by
      personal interviews on a pre-tested, semi-structured questionnaire. The questions
      covered menstrual problems, regularity of menses in last three cycles of
      menstruation and the effect of these problems on the daily routine. Analysis was
      done using SPSS version 12. Percentages were calculated for drawing inferences.
      RESULTS: More than a third (35.9%) of the study subjects were in the age group 13
      15 years followed by 17-19 years, 15-17 years respectively. Mean age of study
      participants was calculated to be 16.2 years. Dysmenorrhea (67.2%) was the
      commonest problem and (63.1%) had one or the other symptoms of Pre-menstrual
      syndrome (PMS). Other related problems were present in 55.1% of study subjects.
      Daily routine of 60% girls was affected due to prolonged bed rest, missed social
      activities/commitments, disturbed sleep and decreased appetite. 17.24% had to
      miss a class and 25% had to abstain from work. Mothers and friends were the most
      common source of information on the issue. CONCLUSION: Screen adolescent girls
      for menstruation related problems and provide them with counseling services and
      relevant information on possible treatment options. Besides, there is a need to
      emphasize on designing menstrual health programmes for adolescents.

PMID- 18334792
TI  - Celiac disease in children with short stature.
AB  - OBJECTIVE: The aim of the present study was to determine the prevalence of celiac
      disease in children with short stature. METHODS: In all children with short
      stature (height more than 2 SD below the mean for age and sex) and normal
      physical examination, attending Motahary pediatric clinic in Shiraz, Iran, from
      2003 till 2005, work-ups were made to find a cause for their short stature and of
      course their serum was assayed for IgG anti-tissue transglutaminase (TTG)
      antibody by ELISA test, as a marker for CD. RESULTS: There were 26 girls and 46
      boys with mean age of 9.8 years. Routine work-up showed microcytic hypochromic
      anemia in four children (5.6%) and giardiasis in five (6.9%). GH stimulation test
      revealed GH deficiency in five children (6.9%). Elevated IgG anti-TTG antibody
      level was detected in two children (2.8%). Duodenal biopsies of these children
      were in favor of celiac disease. CONCLUSION: Although, the prevalence of CD in
      this study was not significantly different (P value = 0.14) from the prevalence
      rate in healthy blood donors in Iran, the findings emphasize the fact that CD
      must be considered in a child with short stature, especially if the height is
      more than 3 SD below the mean for sex and age, even in the absence of
      gastrointestinal symptoms. In conclusion, the measurement of anti-TTG antibody
      should be included in the diagnostic evaluation of children with short stature.

PMID- 18334793
TI  - NPHS2 mutations.
AB  - OBJECTIVE: To uncover the frequency and the spectrum of NPHS2 mutations in
      Egyptian children with non familial steroid-resistant nephrotic syndrome (SRNS).
      METHODS: Sixteen patients were screened by PCR-single-strand conformation
      polymorphism analysis of NPHS2 gene followed by direct sequencing. RESULTS: NPHS2
      mutations were evident in four patients (25%) who were bearing four novel
      mutations including two frame shift mutations (R238fs and P45fs) and two missense
      mutations (I136L and F216Y). There were no phenotypic or histological
      characteristics of patients bearing NPHS2 mutations, apart from the earlier onset
      of the disease, compared to those who were not bearing mutations. CONCLUSION:
      NPHS2 mutations are prevalent in Egyptian children with non-familial SRNS and
      this may in part explain the less favorable prognosis reported in these patients.

PMID- 18334794
TI  - Asthma in patients with atopic dermatitis.
AB  - OBJECTIVE: This cross-sectional study was designed to estimate the frequency of
      asthma in patients with atopic dermatitis (AD), and its related factors. METHODS:
      The study population consisted of 236 patients with AD who were referred to
      Children Medical Center in 1997-2002 and their diagnosis was based on Hanifin &
      Rajka criteria. Severity of AD was categorized based on Severity Scoring of
      Atopic Dermatitis (SCORAD) index. Asthma was diagnosed with medical history and
      clinical examination (three or more episodes of wheezing and/or dyspnea and/or
      cough after 1 year old). The patients were divided in two groups according to
      having or not having asthma. RESULTS: The mean age of patients with AD was
      38.67+/-2.68 month and the mean age at onset of asthma was 20+/-2.5 month. The
      frequency of asthma in AD patients was 27.5%. The mean of SCORAD in nonasthmatic
      patients was 52.27 +/- 2.52 and in asthmatic patients was 56.2+/- 4.2 (P= 0.4).
      The mean of duration of breastfeeding in asthmatic patients was 12.2+/-1.6 month
      and in non-asthmatic patients was 11.16+/-6.3 month (P = 0.87). There was no
      significant difference between asthmatic patients and others in serum IgE levels
      (P = 0.65) and blood eosinophil count. (P = 0.49). CONCLUSION: These results
      confirmed that development of asthma in patients with AD is more than normal
      population and AD can be a significant predisposing factor to developing asthma
      but the causative factors are not clear.

PMID- 18334795
TI  - Spectrum of primary immune deficiency at a tertiary care hospital.
AB  - OBJECTIVE: To report various primary immune deficiencies diagnosed in children at
      a tertiary care hospital, their clinical manifestations and laboratory profile.
      METHODS: Case records of children diagnosed to have primary immunodeficiency
      disorders over a period of 24 months at a tertiary care hospital in northern
      India were evaluated. RESULTS: Twenty-seven children (M: F=3.5: 1) with mean age
      of 5.4 +/- 4.6 yrs (2 mo-16 yr) were diagnosed to have primary immunodeficiency.
      Thirteen children had chronic granulomatous disease (CGD), 4 had severe combined
      immunodeficiency (SCID), 4 had hypogammaglobulinemia, 2 had Ataxia
      telangiectasia, and one each had DiGeorge syndrome, Wiskott Aldrich syndrome,
      hyper IgM syndrome and leukocyte adhesion defect. Common mode of presentation
      were recurrent/ persistent pneumonia in 19, recurrent/ persistent diarrhea in 10,
      deep seated abscesses in 8, allergy in 3, disseminated tuberculosis infection in
      2, extensive fungal infections in 2 and 1 each of disseminated cytomegalovirus
      (CMV) infection, disseminated BCG disease, otitis media and meningitis. Family
      history of sibling deaths was elicited in 2 families. Infectious agents were
      isolated in 16 cases. CONCLUSION: From a single center 27 patients with primary
      immune deficiency could be identified by chart review, suggesting need for high
      index of suspicion for diagnosis of primary immune deficiency in India. Though
      the exact prevalence is not known there is need to make a registry to document
      the magnitude of problem of these disorders.

PMID- 18334796
TI  - Seizures in the newborn.
AB  - Seizures in the newborn period constitute a medical emergency. Subtle seizures
      are the commonest type of neonatal seizures, other types being clonic, tonic, and
      myoclonic. Myoclonic seizures carry the worst prognosis in terms of long-term
      neurodevelopmental outcome. Hypoxic-ischemic encephalopathy is the most common
      cause of neonatal seizures. Multiple etiologies often co-exist in neonates and
      hence it is essential to rule out conditions such as hypoglycemia, hypocalcemia,
      and meningitis before initiating specific therapy. A comprehensive approach for
      management of neonatal seizures has been described.

PMID- 18334797
TI  - Jaundice in the newborns.
AB  - Hyperbilirubinemia is the commonest morbidity in the neonatal period and 5-10% of
      all newborns require intervention for pathological jaundice. Neonates on
      exclusive breast-feeding have a different pattern and degree of jaundice as
      compared to artificially fed babies. Latest guidelines from the American Academy
      of Pediatrics (AAP) for management of jaundice in a normal term newborn have been
      included in the protocol. Separate guidelines have been provided for the
      management of jaundice in sick term babies, preterm and low birth weight babies,
      for hemolytic jaundice and prolonged hyperbilirubinemia.

PMID- 18334798
TI  - Hypocalcemia in the newborn.
AB  - Healthy term babies undergo a physiological nadir in serum calcium levels by 24
      48 hours of age. The nadir may be related to the delayed response of parathyroid
      and calcitonin hormones in a newborn. This nadir may drop to hypocalcemic levels
      in high-risk neonates including infants of diabetic mothers, preterm infants and
      infants with perinatal asphyxia. The early onset hypocalcemia which presents
      within 72 hours, requires treatment with calcium supplementation for at least 72
      hours. In contrast, late onset hypocalcemia usually presents after 7 days and
      requires long term therapy. Ionized calcium is crucial for many biochemical
      processes and total serum calcium is a poor substitute for the diagnosis of
      hypocalcemia.

PMID- 18334799
TI  - Four limb phocomelia.

PMID- 18334800
TI  - Management of infants with intra-uterine growth restriction.
AB  - Intra-uterine growth restriction (IUGR) contributes to almost two-thirds of LBW
      infants born in India. Poor nutritional status and frequent pregnancies are
      common pre-disposing conditions in addition to obstetric and medical problems
      during pregnancy. Growth restriction may be symmetrical or asymmetrical depending
      on the time of insult during pregnancy. The pathological insult in an
      asymmetrical IUGR occurs during the later part of the pregnancy and has a brain
      sparing effect. Common morbidities are more frequent in < 3rd percentile group as
      compared to 3rd-10th percentile group. Guidelines for management of IUGR neonates
      in these two groups have been provided in the protocol.

PMID- 18334801
TI  - Post-resuscitation management of asphyxiated neonates.
AB  - Inspite of major advances in monitoring technology and knowledge of fetal and
      perinatal medicine, perinatal asphyxia is one of the significant causes of
      mortality and long term morbidity. Data from National Neonatal Perinatal Database
      suggests that perinatal asphyxia contributes to almost 20% of neonatal deaths in
      India. "Failure to initiate or sustain respiration after birth" has been defined
      as criteria for the diagnosis of asphyxia by WHO. Perinatal asphyxia results in
      hypoxic injury to various organs including kidneys, lungs and liver but the most
      serious effects are seen on the central nervous system. Levene's classification
      is a useful clinical tool for grading the severity of hypoxic ischemic
      encephalopathy. Good supportive care is essential in the first 48 hours after
      asphyxia to prevent ongoing brain injury in the penumbra region. Strict
      monitoring and prompt correction is needed for common problems including
      temperature maintenance, blood sugars, blood pressure and oxygenation.
      Phenobarbitone is the drug of choice for the treatment of convulsions.

PMID- 18334802
TI  - Caffey disease with raised immunoglobulin levels and thrombocytosis.
AB  - Infantile cortical hyperostosis (Caffey disease) is characterized by radiological
      evidence of cortical hyperostosis, soft tissue swellings, fever and irritability.
      We report a case of Caffey disease highlighting its presentation with
      thrombocytosis and high serum immunoglobulin level to alert physicians to use
      steroids cautiously in view of the known thrombocythemic effect of the drug.
      Raised Immunoglobulin also suggests that this syndrome could be infectious in
      origin.

PMID- 18334803
TI  - Infantile masturbation and paroxysmal disorders.
AB  - A recurrent paroxysmal presentation in children leads to different diagnoses and
      among them are neurologic and cardiac etiologies. Infantile masturbation is not a
      well known entity and cannot be differentiated easily from other disorders. Aim
      of this study is to elucidate and differentiate this condition from epileptic
      seizures. We report 3 cases of 10 to 30 mth old girls of infantile masturbation
      that their symptoms initiated at 2, 3 and 8 mth of age. These present with
      contraction and extension of lower extremities, scissoring of legs, perspiration,
      changing face color. In 2 cases body rocking and legs rubbing initiated then
      there after. Masturbation is one of the paroxysmal non-epileptic conditions of
      early infancy and is in differential diagnosis of epileptic seizures.

PMID- 18334804
TI  - Hypophosphatasia associated with pseudotumor cerebri and respiratory
      insufficiency.
AB  - We report a 3-month-old male with infantile hypophosphatasia who later developed
      Pseudotumor cerebri. At the age of 3 months, he was referred to our hospital
      because of pneumonia and respiratory insufficiency. He had short extremities, and
      radiographs of the bones were consistent with lack of metaphyseal mineralization
      and bowed lower extremities. Vomiting and bulging fontanelle developed 3 months
      after admission, and CSF opening pressure was notably high at 430 mm/H2O.
      Hypophosphatasia is a very rare cause of pseudotumor cerebri. This report is the
      first case where PTC is associated with hypophosphatasia and responded well to
      corticosteroid therapy.

PMID- 18334805
TI  - Fraser-cryptophthalmos syndrome with colonic atresia.
AB  - Fraser cryptophthalmos syndrome is a severe genetic disorder comprising of
      cryptophthalmos, syndactyly and genitourinary abnormalities. Gastrointestinal
      malformations are also increasingly being described. We describe a neonate with
      this syndrome having colonic atresia leading to cecal rupture and
      pneumoperitoneum.

PMID- 18334806
TI  - Infected chylothorax caused by Escherichia coli in a non- immunocompromised
      child.

PMID- 18334807
TI  - Prognostic value of direct bilirubin in neonatal hyperbilirubinemia.

PMID- 18334808
TI  - [Concerning the individual, subjective and integrative in complementary
      medicine].

PMID- 18334809
TI  - Acupuncture: specific and non-specific effects.

PMID- 18334810
TI  - An updated systematic review with meta-analysis for the clinical evidence of
      silymarin.
AB  - BACKGROUND: The potential benefit of silymarin (special extract from the fruits
      of Silybum marianum) in the treatment of liver diseases remains a controversial
      issue. METHODS: For this systematic review electronic databases identified 65
      papers for the search terms silymarin, silibinin, silicristin or milk thistle and
      clinical trial. Only 19 complied with the criteria'double-' or 'single-blind'.
      These publications were analysed from a clinical point of view and meta-analytic
      calculations were performed. RESULTS: The clinical evidence ofa therapeutic
      effect of silymarin in toxic liver diseases is scarce. There is no evidence of a
      favourable influence on the evolution of viral hepatitis, particularly hepatitis
      C. In alcoholic liver disease, comparing with placebo, aspartate aminotransferase
      was reduced in the silymarin-treated groups (p = 0.01) while alkaline phosphatase
      was not. In liver cirrhosis, mostly alcoholic, total mortality was 16.1% with
      silymarin vs. 20.5% with placebo (n.s.); liver-related mortality was 10.0% with
      silymarin vs. 17.3% with placebo(p = 0.01). CONCLUSIONS: Based on the available
      clinical evidence it can be concluded - concerning possible risks /probable
      benefits - that it is reasonable to employ silymarin as a supportive element in
      the therapy of Amanita phalloides poisoning but also (alcoholic and grade Child
      'A') liver cirrhosis. A consistent research programme, consolidating existing
      evidence and exploring new potential uses,would be very welcome.

PMID- 18334811
TI  - [Adjuvant simultaneous mistletoe chemotherapy in breast cancer--influence on
      immunological parameters, quality of life and tolerability].
AB  - INTRODUCTION: The objective of this feasibility study was to identify suitable
      surrogate parameters for a randomized confirmative trial with mistletoe treatment
      in patients with breast cancer. Tolerability,quality of life, hematological and
      immunological parameters were evaluated during postoperative chemotherapy.
      PATIENTS AND METHODS: This prospective open 2-armed non-randomized study compared
      33 patients with primary breast cancer during adjuvant chemotherapy (CMF or EC)
      and simultaneous treatment with Iscador M 5 mg spezial (IM spez) with 33 controls
      without mistletoe. Before and 14 days after chemotherapy hematology, lymphocyte
      subpopulations, stimulability of lymphozytes and quality of life(EORTC QLQ-C30,
      BR23) were assessed. RESULTS: Although there was a slight increase in
      thrombocytes within normal values (p =0.01), no clinically important laboratory
      parameter was favorable in the mistletoe group during the trial. There was no
      difference in immuno suppression due to chemotherapy. We found a lower frequency
      of nausea/vomiting and systemic therapy side effects (EORTC)during add-on-therapy
      with mistletoe (p = 0.02 each). Glucocorticoidco treatment in the mistletoe group
      was less frequent (p = 0.006), as well. In general, the add-on-therapy was well
      tolerated, taking into account that dose reduction was often necessary at the
      beginning of the chemotherapy because of large local reactions at the site of the
      injections. Therefore, blinding seems impossible if treatment with mistletoe and
      chemotherapy is started more or less simultaneously. CONCLUSIONS: Reductions in
      quality of life seem to be smaller during add-on-therapy with mistletoe.
      Laboratory parameters showed no difference compared to the control group. Quality
      of life and reduction of glucocorticoid cotreatment should be further evaluated.

PMID- 18334812
TI  - [Rxtrinsic determinants for using complementary medical therapies].
AB  - BACKGROUND: Numerous studies have explored intrinsic factors that influence the
      use of complementary and alternative medicine (CAM). Extrinsic determinants of
      patients' choice of therapy have seldom been explored. OBJECTIVE: This study
      analyzes the effects of extrinsic determinants on the first-time use of CAM.
      Furthermore, it analyzes how extrinsic determinants influence the choice of
      particular CAM methods and the frequency of CAM use. MATERIALS AND METHODS: The
      analysis bases on a data set generated by a survey using standardized
      questionnaires. 31.8% out of a1,000-patient sample responded. 86.6% of the
      respondents were aged 21-60 years, 79.5% were female. The analysis employs
      descriptive statistics, univariate tests and multivariate fractional logit
      models. RESULTS: Recommendations by friends and family are the strongest
      determinant of first time use of CAM. The strongest determinant of the choice ofa
      particular therapy is its perceived efficacy. Patients with as trong preference
      for effective therapies use CAM more frequently(OR 1.687; 90% CI 1.040-3.378). In
      particular, these patients use phytotherapy (1.787; 1.040-3.372),
      homeopathy(2.282; 1.161-10.806) and traditional Chinese medicine(TCM) (2,386;
      1,421-4,396) more frequently. Patients with a strong preference for physicians'
      recommendations use manipulative therapies more frequently (1,610; 1,177
      2,374),and energetic therapies less frequently (0,451; 0.261-0,693). Patients
      valuing high-profile therapies (0,714; 0.585-0,883)and expert recommendations
      (0,608; 0.508-0,732) use CAM less frequently. Socio-demographic characteristics
      do not affect the total usage of CAM. CONCLUSION: The usage pattern of CAM does
      not only depend on intrinsic factors. It is also determined by extrinsic factors.

PMID- 18334813
TI  - A review of the literature in applied and specialised kinesiology.
AB  - INTRODUCTION: Kinesiology is a diagnostic, therapeutic complementary therapy
      utilising subtle change in manual muscle testing results to evaluate the body's
      energetic balance and select healing modalities. Anecdotal evidence suggests
      kinesiology is helpful, therefore we wished to critically review the literature.
      AIMS: (1) To ascertain if diagnostic accuracy including inter-examiner
      reliability has been established. (2) To review whether there is evidence for its
      therapeutic effectiveness. (3) To critically assess the quality of relevant
      studies. METHODS: Electronic databases were searched. Diagnostic accuracy studies
      were analysed and scored for methodological quality and quality of reporting
      using the quality assessment tool for studies of diagnostic accuracy included in
      systematic reviews (QUADAS) and the Standards for Reporting of Diagnostic Studies
      (STARD). Clinical studies were analysed for methodological quality using the
      JADAD scale and for quality of reporting using the Consolidated Standards of
      Reporting Trials (CONSORT). RESULTS: 22 original relevant studies were
      identified. Their methodology was poor. Items reported on QUADAS scored 1-11 out
      of a possible 14, STARD scores were between 6-13 out of 25, JADAD scores were all
      0 out of 5 and CONSORT 4-6 out of 22. Consequently, we were unable to answer any
      of our research questions. CONCLUSION: There is insufficient evidence for
      diagnostic accuracy within kinesiology, the validity of muscle response and the
      effectiveness of kinesiology for any condition. The standards of reporting were
      low. We recommend a pragmatic study of the effectiveness of kinesiology as the
      most appropriate initial step to determine whether kinesiology has any clinical
      value.

PMID- 18334814
TI  - FGF2 signaling in mouse embryonic fibroblasts is crucial for self-renewal of
      embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) can be maintained undifferentiated
      (pluripotent) or differentiated to basically all functional cell types, depending
      on the culture conditions used. Culture of hESCs in the presence of medium
      conditioned by mouse embryonic fibroblasts (MEFs) can be used to keep hESCs
      undifferentiated. This observation suggests that MEFs produce factors required
      for the pluripotency of hESCs. The data presented here show that fibroblast
      growth factor 2 (FGF2) treatment of MEFs is crucial for the production of these
      factors. To identify the potential factors that are expressed in the presence of
      FGF2 in MEFs, a global expression profile analysis using microarrays was
      performed. This analysis indicated that 17 secreted factors are downregulated in
      the absence of FGF2. These factors include several ligands for known signaling
      receptors, extracellular proteases and components of the extracellular matrix,
      that may all be involved in signaling events. Surprisingly, we found that
      selective blocking of extracellular signal-regulated kinase (ERK) signaling by
      the MAPK/ERK kinase (MEK) inhibitor U0126 affected the expression of only some of
      the FGF2-regulated genes, suggesting FGF2-induced pathways that are independent
      of ERK signaling. It has been shown recently that activation of Activin/Nodal
      signaling and inhibition of bone morphogenetic protein signaling are required for
      the maintenance of pluripotency. Accordingly, among the 17 FGF2-regulated genes
      we found inhibin beta B that can lead to the assembly of Activin B and gremlin 1
      that codes for an antagonist of bone morphogenetic proteins. This study
      identifies potentially important factors involved in the maintenance of
      pluripotency in hESCs and may allow the development of defined culture conditions
      without contaminating material from animal cells.

PMID- 18334815
TI  - Serum lipids and postprandial glucose and insulin levels in hyperlipidemic
      subjects after consumption of an oat beta-glucan-containing ready meal.
AB  - BACKGROUND/AIMS: To investigate whether a daily intake of a nutrient-balanced
      ready meal containing 4 g of oat beta-glucans lowers total cholesterol (T-C) and
      low-density-lipoprotein cholesterol (LDL-C) in hyperlipidemic subjects and to
      evaluate its effect on postprandial glucose and insulin concentrations. METHODS:
      A parallel, placebo-controlled trial was carried out in 43 healthy men and women
      with elevated serum cholesterol levels. During the 3-week run-in period, all
      subjects consumed daily a ready-meal soup, low in energy and fat and high in
      fiber but without oat beta-glucans. Subjects were then randomly assigned for the
      following 5-week intervention period to either continue consumption of the
      control soup or an equal soup supplemented with beta-glucan. RESULTS: Consumption
      of the beta-glucan-enriched ready meal decreased T-C (0.22 +/- 0.41 mmol/l) and
      LDL-C (0.16 +/- 0.36 mmol/l), but the reductions were not significantly lower
      compared with control. After a meal with beta-glucan soup, neither postprandial
      glucose nor insulin concentrations were significantly different from those after
      a control soup. CONCLUSION: A daily dose of 4 g of oat beta-glucans incorporated
      into a healthy ready meal did not significantly lower T-C and LDL-C compared with
      an equal ready meal without beta-glucans. Thus, if a food product fulfils general
      healthy dietary recommendations it may not necessarily be a candidate for
      supplementation with beta-glucans.

PMID- 18334816
TI  - Wetter and better? Changes in associations between drunkenness and other problem
      behaviors among Norwegian youth.
AB  - BACKGROUND/AIMS: The consumption of alcohol and the frequency of intoxication
      among Norwegian youth increased significantly from 1992 to 2002, and we thus
      asked what, if anything, can be expected to happen to rates of other problem
      behaviors when heavy drinking becomes more widespread? Do such aggregate level
      changes in alcohol use imply that individual level associations between
      drunkenness and behavioral deviance change as well? METHOD: School-based surveys
      of 16- to 19-year-old Norwegians that were carried out in 1992 (n = 4,744,
      response rate 97%) and 2002 (n = 5,458, response rate 92%). RESULTS: Contrary to
      rates of drunkenness, the level of theft/pilfering declined from 1992 to 2002,
      while rates of aggressive behavior and school misconduct remained unchanged. We
      assumed that heavy-drinking adolescents were relatively less deviant with regard
      to non-violent problem behaviors when the youth culture was relatively 'wet'
      (2002) as compared to the period when it was much 'drier' (1992) and revealed
      that this was the case. However, the link between drunkenness and aggressive
      behavior was equally strong at both assessments. CONCLUSION: Differential
      temporal trends in the associations between drunkenness and various problem
      behaviors may reflect variations with respect to the etiological significance of
      alcohol use on such behaviors.

PMID- 18334817
TI  - Spreading or concentrating drinking occasions--who is most at risk?
AB  - AIMS: (a) To compare acute negative consequences for people who drink a given
      amount of alcohol on few occasions (concentrators) per week in comparison with
      the consequences for people who drink the same amount on more days in a week
      (spreaders). (b) To investigate whether these associations are cross-culturally
      stable. METHODS: Analysis is based on general population surveys of adults
      conducted in 7 European countries. RESULTS: It appeared that more drinking
      occasions in many countries lead to more consequences independent of the volume
      consumed. Risky single-occasion drinking was to be associated with higher risks
      for immediate health consequences and legal problems, accidents and fights. Among
      older respondents the same frequency pattern appeared, with the exception of
      immediate health consequences among women. Hence, more regular drinking seemed to
      have more beneficial effects on older individuals compared to younger ones, which
      may be related to the different drinking situation: younger people mostly
      drinking outside the home. Amongst the younger people, frequent drinking seemed
      to be associated with more acute consequences. Cultural and methodological
      variations must be taken into account. CONCLUSION: Even so, it is concluded that
      the credibility of these findings is strengthened by differences in the methods
      of the surveys.

PMID- 18334818
TI  - Mortality in opioid-maintained patients after release from an addiction clinic.
AB  - AIM: To investigate the mortality rate in a cohort of 269 opioid-dependent
      patients and the outcome of survivors meeting DSM-IV criteria for opioid
      dependence. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients enrolled
      in synthetic opioid maintenance therapy during a time frame from 1998 to 1999
      originally at the Addiction Clinic and then discharged to general practitioners.
      METHODS: Structured interviews (Europ-ASI), urinalysis at time of interview as
      well as autopsy findings from deceased patients. RESULTS: After six mailings,
      information from 147 (54.6%) patients was gained. 85 patients (31.6%) were
      interviewed. From these 76.5% (n = 65) were still enrolled in maintenance
      therapy, 18.8% (n = 16) were drug-free and 4.7% (n = 4) relapsed. From 29
      fatalities, 37.9% died of intoxication with illicit substances, 34.5% related to
      AIDS and 27.6% of somatic complications. The Standardized Mortality Ratio (SMR)
      was 29.13 (95% CI = 19.27-44.04). A higher lifetime frequency of hospitalization,
      less working days and a lack of social relationships were factors associated with
      high mortality. CONCLUSIONS: The study confirms the high mortality rate in this
      patient group and supports the importance of maintenance therapy. Although great
      efforts were undertaken in locating patients, about 45% of the target group could
      not be located.

PMID- 18334819
TI  - Route of administration of illicit drugs among remand prison entrants.
AB  - AIMS: To describe the self-reported routes of administration of illicit drugs
      among subjects entering a remand prison and the different drugs used by this
      population. METHODS: A cross-sectional study, with a sample of 770 subjects, was
      conducted in Geneva (Switzerland). Participants were assessed with the semi
      structured interview from the Council of Europe Pompidou Group multi-city study.
      RESULTS: 428 (55.6%) subjects admitted to having used illicit drugs during the 3
      months prior to entry. Amongst these illicit drug users, 54.7% took several
      drugs. Injectable drugs (heroin, cocaine or illicit benzodiazepines) were taken
      by 75.7% of drug users but the majority (84.1%) declared that they had not
      injected drugs during the 3 months prior to entering prison. 68 subjects (8.8% of
      the total sample) declared that they had injected drugs during the 3 months prior
      to entering prison, either alone or in association with other methods.
      CONCLUSION: By extrapolation it is possible to suggest that about 200 intravenous
      drug users entered the remand prison in Geneva in 1 year. This confirms the need
      for prison health services to implement a policy of treatment, prevention and
      education adapted to patterns of drug use in the local context.

PMID- 18334820
TI  - Quality of life in patients receiving opioid maintenance therapy. A comparative
      study of slow-release morphine versus methadone treatment.
AB  - BACKGROUND/AIMS: In recent years, quality of life (QoL) assessments have proved
      useful for evaluating and comparing drug treatment programs. To compare QoL of
      patients maintained on methadone versus slow-release morphine, a prospective,
      randomized, double-blind, double-dummy, cross-over study was conducted. METHODS:
      Over two 7-week study phases, participants received either oral slow-release
      morphine capsules followed by methadone oral solution or vice versa. QoL status
      was assessed at baseline, week 7, and week 14 using the German version of the
      Lancashire Quality of Life Profile. RESULTS: No statistically significant
      difference was found between methadone and slow-release morphine in any QoL
      domain. A significant time effect for nearly all QoL domains was observed after
      14 weeks of opioid medication, independent of the chosen drug (general well
      being, p < 0.001; mental health, p = 0.001; general state of health, p = 0.018;
      leisure time at home, p = 0.034; leisure time out of the home, p = 0.008).
      Furthermore, this study revealed that even short-term maintenance yields
      significantly higher QoL scores in the important domain of general well-being.
      CONCLUSION: These results indicate that slow-release morphine has effects
      comparable to methadone on patient-reported QoL data and is thus a promising
      option for treatment of opioid-dependent subjects.

PMID- 18334821
TI  - Partner effects and bidirectional parent-child effects in family alcohol use.
AB  - INTRODUCTION: The current study investigated partner effects and bidirectional
      parent-child effects in family alcohol use. METHODS: A full family, longitudinal
      design was used to test the hypotheses. Participants were 428 families, including
      mothers, fathers, and 2 children. Associations were measured over two waves with
      a 2-year interval, by means of structural equation modeling. RESULTS: Whereas
      alcohol use of the younger children was affected by alcohol use of both parents,
      alcohol use of the older children was only affected by alcohol use of mother.
      Moreover, although the effects were small, alcohol use of older children affected
      later alcohol use of both parents. CONCLUSIONS: Associations between alcohol use
      of parents and children seem to be bidirectional. Future studies are needed to
      find out whether these findings are incidental or structural. If the effects are
      structural, potential underlying reciprocal processes within the family play a
      role in the development of adolescent alcohol use.

PMID- 18334822
TI  - Pregnancy and birth under maintenance treatment with diamorphine (heroin): a case
      report.
AB  - BACKGROUND: Heroin-assisted treatment (HAT) is a new form of treatment for heroin
      dependent patients not responding to conventional interventions such as methadone
      maintenance treatment. No pregnancies or births under HAT have been reported
      until now. CASE: The pregnancy course of a 31-year-old severely dependent multi
      morbid woman receiving HAT and the birth of a healthy baby after premature
      delivery is described. HAT helped to reduce the use of illicit substances both
      before and during pregnancy. The neonatal abstinence syndrome was clinically well
      compensated. CONCLUSION: HAT seems to be feasible in pregnant women and normal
      birth is possible under HAT, which therefore may act as a harm reduction measure
      for polydrug-using pregnant women not responding to methadone maintenance
      treatment.

PMID- 18334823
TI  - Serum fetuin-a concentration and endothelial dysfunction in chronic kidney
      disease.
AB  - BACKGROUND: Defective endothelial function, an initial step in the development of
      atherosclerotic plaque, is prevalent in moderate to advanced chronic kidney
      disease (CKD). In this study, the investigators hypothesized that fetuin-A, a
      calcification inhibitor, is a novel risk factor for the development of
      endothelial dysfunction in patients. METHODS: 198 nondiabetic patients with a
      mean age of 44.0 +/- 12.4 years and with different stages of CKD were studied. In
      addition to a detailed metabolic panel, flow-mediated dilatation assessed by high
      resolution brachial ultrasonography was performed to determine endothelial
      dysfunction. Carotid intima-media thickness was also estimated by
      ultrasonography. Serum fetuin-A concentrations were determined by using a human
      ELISA method. RESULTS: Endothelial dysfunction was observed in all stages (1-5)
      of CKD and worsened in parallel to the reduction in estimated glomerular
      filtration rate. Serum fetuin-A concentrations were also found to be decreased in
      all but stage 1 CKD. On multiple regression analysis, endothelial dysfunction was
      independently associated with fetuin-A (beta = 0.745, p < 0.001) and intact
      parathyroid hormone concentrations (beta = -0.216, p < 0.001). CONCLUSION: These
      data in a selected cohort of CKD patients indicate that fetuin-A may be one of
      the contributing factors for the development of endothelial dysfunction in CKD
      patients.

PMID- 18334824
TI  - The third World Kidney Day: looking back and thinking forward.

PMID- 18334825
TI  - Hospitalizations for incident stroke in Shunde District, Foshan, South China.
AB  - BACKGROUND/AIM: Stroke is a leading cause of mortality and morbidity in China.
      Accurate diagnosis of stroke type requires advanced imaging techniques. However,
      CT scan and MRI were not widely used in China until the middle 1990s. We estimate
      the stroke incidence based on stroke hospitalizations in Shunde District, Foshan,
      south China. METHODS: Stroke hospitalization rates were calculated for different
      age strata using the number of cases observed and the population size of Shunde
      in 2005 and 2006. RESULTS: The age-adjusted hospitalization rates (per 100,000
      person-years) for all strokes were 57.4 overall, 65.1 for males and 50.0 for
      females, standardized according to Segi's world population. CONCLUSION: The
      stroke incidence appeared to be lower in Shunde than those reported for other
      parts of China.

PMID- 18334826
TI  - Incidence and prevalence of amyotrophic lateral sclerosis in Uruguay: a
      population-based study.
AB  - OBJECTIVE: To determine the incidence and prevalence of amyotrophic lateral
      sclerosis (ALS) in the Republic of Uruguay. METHODS: The study was performed in
      Uruguay (3,241,003 inhabitants) during a 2-year period (2002-2003). To ensure
      complete case ascertainment, multiple sources of information were used, including
      all the neurologists, other medical specialties, general physicians,
      neurophysiology laboratories, hospital medical records and death certificates.
      ALS diagnosis was based on El Escorial criteria. Although all patients with motor
      neuron disease were enrolled in the follow-up, only probable and definite cases
      are included in the study. RESULTS: Between January 1st, 2002, and December 31st,
      2003, 89 new patients were diagnosed with probable or definite ALS. The mean
      annual incidence rate was 1.37 per 100,000 persons. The incidence was higher for
      men (1.95) than for women (0.84) with a male to female ratio of 2:1. For both,
      the incidence increased throughout the years showing a peak in the 65-74 age
      group among men and the 55-64 age group among women. Mean age at onset of ALS
      disease was 58.7 years. The estimated mean annual incidence for ALS calculated by
      the capture recapture method was 1.42 (95% CI, 1.13-1.72). On December 31st,
      2002, the crude prevalence was 1.9 per 100,000 inhabitants. CONCLUSIONS: ALS
      incidence is within a narrow range across countries despite the genetic,
      environmental and socioeconomic differences when similar prospective design,
      diagnosis criteria and data analyses are applied.

PMID- 18334827
TI  - Evaluating the quality of longitudinal statistical applications in original
      publications on Alzheimer's disease.
AB  - BACKGROUND/AIMS: To evaluate the quality of longitudinal statistical applications
      in published studies on Alzheimer's disease (AD). METHODS: A 21-item instrument,
      the Quality of Longitudinal AD Studies (QLADS), was developed by the research
      team (4 biostatisticians, 1 neuroepidemiologist, and 1 neurologist). All items
      were extensively discussed within the team for content validity. After pilot
      testing on 5 publications, the instrument was revised and tested for reliability
      with a sample of 40 published longitudinal AD studies randomly sampled from
      MEDLINE. RESULTS: Item-specific test-retest reliability coefficients for QLADS
      ranged from 0.53 to 1.00 with the associated standard error (SE) ranging from
      0.02 to 0.13. The test-retest reliability for the overall score over the 21 items
      was high (intraclass correlation coefficient (ICC) = 0.94, 95% CI 0.90, 0.97).
      Item-specific inter-rater reliability coefficients for QLADS ranged from 0.46 to
      1.00 with the associated SE ranging from 0.07 to 0.18. The inter-rater
      reliability for the overall score was also high (ICC = 0.87, 95% CI 0.77, 0.93).
      CONCLUSIONS: This study indicates that the quality of longitudinal statistical
      applications in AD publications can be reliably assessed.

PMID- 18334828
TI  - Incidence of hospital-treated traumatic brain injury in the Oslo population.
AB  - BACKGROUND: The aim of this prospective, population-based study is to present the
      incidence of hospital-treated traumatic brain injury (TBI) in Oslo, Norway, and
      to describe the severity of brain injuries and outcome of the patients' acute
      medical care. METHODS: Data were obtained from hospital admission registers and
      medical records from May 2005 to May 2006. The initial severity of TBI was
      measured by the Glasgow Coma Scale. The region is urban with a population of
      534,129. RESULTS: The 445 patients identified represent an annual incidence of
      83.3/100,000. The median age was 29 years. The male:female ratio was 1.8:1.0. The
      highest incidence of TBI hospitalizations was found in the elderly males and the
      youngest children. The most common causes of TBI were falls (51%) and transport
      accidents (29.7%). Intracranial lesions were found more often in the elderly. The
      case fatality rate was 2.0/100 hospitalized patients and was highest in the
      elderly. CONCLUSIONS: The incidence of hospital-treated TBI in this study is
      considerably lower than that found in previous studies from Norway and
      Scandinavia. Despite the apparent decline in TBI hospitalization rates, our
      findings should also draw attention to the need for more effective preventive
      programmes related to falls. Studies that assess long-term consequences of TBI in
      elderly patients are also needed.

PMID- 18334829
TI  - A randomized phase II trial of pemetrexed plus irinotecan (ALIRI) versus
      leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of
      locally advanced or metastatic colorectal cancer.
AB  - BACKGROUND: This multicenter, randomized trial compared overall response rate
      between pemetrexed plus irinotecan (ALIRI) and leucovorin-modulated 5
      fluorouracil plus irinotecan (FOLFIRI) in patients with advanced colorectal
      cancer. Secondary objectives included overall and progression-free survival,
      duration of response, toxicities, and biomarkers. PATIENTS AND METHODS: ALIRI
      patients received pemetrexed 500 mg/m(2) and irinotecan 350 mg/m(2) with vitamin
      supplementation on day 1 of each 21-day cycle. FOLFIRI patients received
      irinotecan 180 mg/m(2) on days 1, 15, 29; on days 1, 2, 15, 16, 29, 30, patients
      received leucovorin 200 mg/m(2), bolus 5-fluorouracil 400 mg/m(2), and 5
      fluorouracil 600 mg/m(2) as 22-hour infusion. RESULTS: Of 132 patients randomly
      assigned, 130 patients (64 = ALIRI, 66 = FOLFIRI) received > or =1 dose of
      treatment. Response rates (ALIRI = 20.0%, FOLFIRI = 33.3%) were not significantly
      different between arms (p = 0.095). Progression-free survival was 5.7 months for
      ALIRI and 7.7 months for FOLFIRI (p < 0.001). Neutropenia, fatigue, diarrhea,
      nausea, and vomiting were the major toxicities. There were 5 drug-related deaths
      (ALIRI = 4, FOLFIRI = 1). Biomarker analysis failed to reveal that any of the 18
      preselected genes were clearly associated with tumor response. CONCLUSIONS:
      Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI
      arm. Progression-free survival on FOLFIRI was significantly longer compared to
      ALIRI. Potential biomarkers capable of predicting response to either regimen in
      advanced or metastatic colorectal carcinoma need further characterization.

PMID- 18334830
TI  - Prognostic factors and prognostic index for chemonaive and gemcitabine-refractory
      patients with advanced pancreatic cancer.
AB  - BACKGROUND: Gemcitabine monotherapy is the cornerstone of the treatment of
      patients suffering from advanced pancreatic cancer (PC). For a few years, new
      chemotherapeutic agents and combinations have been under validation. The use of
      such treatment makes it necessary to determine factors that could predict
      survival time. PATIENTS AND METHODS: To identify factors that predict survival
      time in chemonaive patients with advanced PC and after gemcitabine failure, a
      retrospective analysis was performed on patients with advanced PC coming from
      phase II and III studies and treated with gemcitabine-based first-line
      chemotherapy. RESULTS: Ninety-nine patients (median age 66 years, range 27-87)
      suffering from pathologically proven unresectable or metastatic adenocarcinoma of
      the pancreas were reviewed. Median overall survival time for the whole population
      was 251 days and progression-free survival in first- and second-line treatment
      was 108 and 67 days, respectively. The Cox regression analysis identified
      aspartate transaminase >53 IU/l, weight loss > or =10% and Karnofsky performance
      status <90 as significant independent negative prognostic factors in first-line
      and CA 19-9 >400 IU/ml and albumin < or =3.5 mg/dl in second-line chemotherapy. A
      prognostic index was calculated from the regression coefficients for each
      independent prognostic factor and used to classify the patients in 3 different
      groups with good, intermediate and poor prognosis. The prognosis index in
      chemonaive and gemcitabine-refractory patients was (Karnofsky performance status
      x 0.52) + (weight loss x 1.10) + (aspartate transaminase x 0.82) and (albumin x
      1.40) + (CA 19-9 x 0.74), respectively. CONCLUSIONS: Predictive factors could be
      identified in first- and second-line treatments, although they require
      prospective validation before they could be used in the design and analysis of
      future clinical trials.

PMID- 18334831
TI  - Colorectal cancer or colon and rectal cancer? Clinicopathological comparison
      between colonic and rectal carcinomas.
AB  - AIMS: The aim of this study was to compare features of colon and rectal cancers
      such as prognosis, clinicopathological features and tumor markers, namely
      carcinoembryonic antigen (CEA), matrix metalloproteinase (MMP)-2 and p27(kip1).
      METHODS: Two hundred and thirty patients with stage I-III colon or rectal cancer
      were retrospectively assessed with the endpoint of recurrence or metastasis after
      curative operation. CEA, MMP-2 and p27(kip1) were studied by immunohistochemistry
      in cancer tissues of all patients. RESULTS: The disease-free 3-year survival rate
      after operation of the total 230 patients was 63.0%. The prognosis of colon
      cancer was significantly better than that of rectal cancer (70.6 vs. 57.0%; p =
      0.017), especially for stage III (p = 0.0059). Multivariate analysis also
      demonstrated that tumor location in the colon or rectum, differentiation, venous
      invasion and the expression of CEA were independent factors for prognosis. The
      hazard of recurrence and metastasis in rectal cancer was 1.564 times that in
      colon cancer. In both groups, there were no statistical differences in age,
      gender, tumor size, tumor gross type, mucin production, tumor differentiation,
      venous invasion, MMP-2 and p27(kip1). CONCLUSION: We investigated prognosis,
      clinicopathological factors, oncogenes and tumor suppressor gene production in
      colon and rectal cancers. The prognosis of colon cancer is better than that of
      rectal cancer, especially for stage III. This study shows some differences
      between colon and rectal cancer.

PMID- 18334832
TI  - Large institutional experience with dose-intensive chemotherapy and stem cell
      support in the management of sarcoma patients.
AB  - BACKGROUND: The prognosis of patients with advanced sarcoma remains poor. Whether
      high-dose chemotherapy with stem cell support improves the long-term outcome for
      these patients or not is controversial. METHODS: We present a large institutional
      experience of sarcoma patients treated with this therapy option. Thirty-eight
      patients with bone (n = 17) and soft tissue sarcomas (n = 21) were included.
      Apart from haematological complications, no WHO grade III-IV complications were
      observed. One patient died due to cardiac arrest after transplantation. RESULTS:
      Following chemotherapy and/or surgery, but prior to high-dose chemotherapy,
      diagnoses were made of: no evidence of disease (NED; n = 12), partial remission
      (n = 17), stable disease (n = 3) and progressive disease (PD; n = 6). Six
      patients died within 8 months due to PD, in 18 patients disease recurred and led
      to death and 13 patients are alive with/without disease. Median progression-free
      survival was 19.1 months (range: 0-121) for all patients, and 48.8 months (range:
      3-121) for 12 patients with NED. CONCLUSION: A subgroup of patients with NED
      before high-dose chemotherapy gained survival benefit. Therefore, we emphasize
      the value of high-dose chemotherapy as a treatment option for younger patients
      with a good performance status in partial or complete remission.

PMID- 18334833
TI  - Pathobiology - exploring the basis of disease.

PMID- 18334834
TI  - siRNA targeting against EGFR, a promising candidate for a novel therapeutic
      application to lung adenocarcinoma.
AB  - OBJECTIVE: To understand the molecular pathogenesis of lung cancer and to
      establish a novel therapeutic application, we examined the genetic alterations in
      lung cancer, and studied the effects of gefitinib and siRNA-mediated knockdown of
      EGFR on lung cancer. METHODS: We analyzed mutations in EGFR, KRAS, TP53, and
      ERBB2 in 198 surgically resected lung cancer specimens. We then analyzed the
      effects of gefitinib and siRNA treatment on lung adenocarcinoma cell lines.
      RESULTS: Mutations in EGFR were found only in adenocarcinoma (35 of 106
      adenocarcinoma), mainly in females (73%). Mutually exclusive mutations of EGFR
      and KRAS genes were observed. Mutations of EGFR were well associated with a
      positive response to gefitinib. Cells with EGFR mutations were very sensitive to
      gefitinib as well as siRNA-mediated knockdown of EGFR, those with KRAS mutations
      responded poorly, and those without mutations of KRAS and EGFR showed moderate
      responses to both treatments. CONCLUSIONS: Our present results imply that (1)
      mutation analyses of EGFR and KRAS provide valuable information about whether or
      not to apply treatments targeting against EGFR and the selection of dosage for
      such treatments, and (2) siRNA-mediated knockdown is effective in lung
      adenocarcinomas with EGFR mutation, probably in those with resistance to
      gefitinib by acquired mutation in EGFR.

PMID- 18334835
TI  - Thrombospondin 1 and its mimetic peptide ABT-510 decrease angiogenesis and
      inflammation in a murine model of inflammatory bowel disease.
AB  - OBJECTIVE: Vascular abnormalities and expression of proangiogenic factors have
      been repeatedly reported in inflammatory bowel disease (IBD). Thrombospondin 1
      (TSP-1) is a protein well known for its antiangiogenic and anti-inflammatory
      properties. Using the dextran sulfate sodium (DSS) model, the role of TSP-1 in
      IBD has been investigated in vivo. METHODS: TSP-1-deficient mice (TSP-1-/-) and
      WT mice were treated with DSS for 7 days. Disease activity indices,
      myeloperoxidase activity (MPO) and histology were analyzed. Microvascular density
      (MVD) was quantified using immunohistochemistry (IMH) with CD31 antibody. TGF
      beta(1), basic FGF, VEGF, TNF-alpha and MMPs protein levels were evaluated by IMH
      and enzyme-linked immunoabsorbent assay (ELISA). Mice were treated with ABT-510
      (Abbott Laboratories), an antiangiogenic TSP peptide, using miniosmotic pumps for
      7 days. RESULTS: TSP-1(-/-) mice had a worse clinical outcome and exhibited
      severe signs of rectal bleeding compared to the WT controls. The TSP-1-/- mice
      showed a higher level of crypt damage and deeper lesions. The grade of
      inflammation and the levels of MPO activity were also significantly higher in
      colons of TSP-1-/- mice. TSP-1-/- mice displayed higher MVD in focal areas of the
      colon after only 3 days of DSS treatment. Furthermore, clinical severity of the
      colitis and angiogenesis was significantly diminished when mice was treated with
      ABT-510. CONCLUSIONS: These findings directly link TSP-1 as a protective factor
      in IBD and suggest antiangiogenesis treatment, including compounds such as ABT
      510 as an adjuvant therapy for IBD.

PMID- 18334836
TI  - Negative regulators of angiogenesis in inflammatory bowel disease: thrombospondin
      in the spotlight.
AB  - Angiogenesis is the growth of new blood vessels. In the two major forms of
      inflammatory bowel disease (IBD), Crohn's disease and ulcerative colitis, robust
      angiogenesis exists, and its blockade may have therapeutic potential, as shown in
      animal models of experimental intestinal inflammation. While abundant literature
      is available on the positive regulators of intestinal pathological angiogenesis,
      e.g. VEGF, b-FGF, IL-8, CD40 and CD40L, almost no data exist on negative
      regulators. Thrombospondin-1 is a negative regulator of angiogenesis, and it
      plays a new role in IBD-associated angiogenesis. In addition, recombinant
      thrombospondin-1 may inhibit pathological angiogenesis and may offer a new
      therapeutic approach to intestinal inflammation.

PMID- 18334837
TI  - Large-scale analysis of cell cycle regulators in urothelial bladder cancer
      identifies p16 and p27 as potentially useful prognostic markers.
AB  - AIMS: We investigated the value of multiple cell cycle markers for their
      prognostic impact on overall survival and recurrence-free survival in urothelial
      carcinoma (UC). METHODS: A tissue microarray consisting of 99 UCs was evaluated
      for the expression of p53, p16, p21, p27, cyclin D1, cyclin E , Bcl-2, Ki-67 and
      PCNA. Statistical analysis was performed applying Kaplan-Meier and Cox regression
      models using receiver operator characteristic curves for determination of
      markers' cutoffs. RESULTS: Expression above the cutoffs of Ki-67, p53 and p27,
      particularly in high-grade and early-stage UC, was associated with worse overall
      survival, while expression of p16 indicated a better outcome in low-grade and low
      stage tumors. Recurrence-free survival was better in patients with high-grade UC
      expressing PCNA, p16 and cyclin E, and low-grade UC expressing Bcl-2 above the
      cutoffs, but worse in all tumors with high Ki-67. CONCLUSION: Cell cycle
      deregulation in UC is complex and the prognostic value of the various involved
      proteins should be differentially regarded with respect to this complexity and
      other tumor characteristics such as grade and stage. Our results point towards
      the role of p16- and p27-associated pathways in tumor progression and indicate
      that, by using standardized approaches for tissue antigen expression, evaluation
      and cutoff determination, single potentially useful prognostic markers could be
      identified.

PMID- 18334838
TI  - Do different disorders in cell cycle regulation account for different biological
      behavior of urothelial and sinonasal inverted papillomas?
AB  - OBJECTIVE: It was the aim of this study to assess the expression of selected cell
      cycle regulation genes in urothelial and sinonasal inverted papillomas (IP).
      METHODS: Archived surgically resected specimens from 18 urothelial and 19
      sinonasal IP were studied immunohistochemically for p16, p53, cyclin D1 and Ki67.
      Staining results were semiquantified and compared between IP and adjacent control
      mucosa (CM). RESULTS: p53 expression did not differ between sinonasal and
      urothelial IP. Although there was a trend of higher p53 expression in IP compared
      with the adjacent CM in sinonasal and urothelial specimens, this trend failed to
      be statistically significant. p16 expression was significantly higher in
      urothelial IP and CM in comparison with their sinonasal counterparts, but did not
      differ significantly between IP and its adjacent CM either in urothelial or
      sinonasal specimens. There were no significant differences in the mean scores for
      cyclin D1 or Ki67. CONCLUSION: The changes in p53 expression seen in both types
      of IP compared with adjacent CM suggest that sinonasal and urothelial IP may
      share some common ground in terms of their evolution. Although p16 appears not to
      be directly involved in the development of sinonasal or urothelial IP, the
      differing recurrence patterns of sinonasal versus urothelial IP may be
      attributable in part to different p16 expression.

PMID- 18334839
TI  - Spatial and phenotypic characterization of vascular remodeling in a mouse model
      of asthma.
AB  - Asthma is a chronic inflammatory disease characterized by airway wall remodeling
      in which vascular remodeling is thought to be a main contributor. Vascular
      endothelial growth factor (VEGF) is known as a major regulator of angiogenesis
      and enhancer of vascular permeability. Here, we define the spatial nature of
      vascular remodeling and the role of VEGF and its receptors (Flt-1 and Flk-1) in
      the allergic response in mice (A/J) susceptible to the development of allergen
      induced airway hyperresponsiveness using morphometric and quantitative
      approaches. Increased vascularity, vasodilatation, and endothelial cell
      proliferation were found in the tracheal and bronchial walls in the early and
      late phases of asthma. Vascular changes were observed not only in small vessels
      but also in larger vessels. In contrast to normal control, lung tissue from the
      asthma model showed dual expression for CD31 and von Willebrand factor in the
      endothelial cells and alpha-smooth muscle actin and desmin in the mural cells of
      the vessels, suggesting a phenotypic and functional transformation. The mRNA
      levels of VEGF isoforms, VEGF(164) and VEGF(188), were significantly increased in
      the tracheal and lung tissue, respectively. In addition, the mRNA level of VEGF
      receptor Flk-1 was significantly increased in the trachea. These results
      establish the existence of vascular remodeling in the airways in a mouse model of
      allergic asthma and support a key role for the expression of unique VEGF isoform
      genes as mediators of structural changes.

PMID- 18334840
TI  - Pediatric extradural spinal tumors.
AB  - We have reviewed 16 children with extradural spinal tumors, both benign and
      malignant, treated from 1998 to 2006 in Sanjay Gandhi Postgraduate Institute of
      Medical Sciences, Lucknow, India. The duration of symptomatology, clinical signs,
      radiological investigations, surgical approach, outcome and histopathological
      variation from the Western world was noted and evaluated. The age of these
      children ranged from 3 to 20 years. There were 11 boys and 5 girls. The duration
      of symptoms was 2-18 months, relatively longer in benign (mean 9.5 months) than
      malignant (mean 4.2 months) tumors. The follow-up ranged from 3 to 72 months and
      patients were graded preoperatively and postoperatively with the McCormick
      Functional Grading System. There was significant improvement in grade III-V
      patients, i.e. 74% of patients were grade III-IV at presentation, and only 35% at
      the last follow-up. There was deterioration from grade III to grade IV in 2
      patients (PNET + metastatic adenocarcinoma) and 2 patients (neuroblastoma +
      Ewing's sarcoma) maintained their grades of IV and V, respectively. There was a
      wide range of histological variants seen in our series and the patients were
      treated primarily with a suitable surgical approach and adjuvant
      chemoradiotherapy, wherever indicated.

PMID- 18334841
TI  - Setting sun eye in normal healthy infants.
AB  - BACKGROUND: The setting sun eye is a common sign associated with severe disorders
      signifying intracranial hypertension. Rarely it can be observed in a healthy
      infant. We conducted this study to evaluate and follow setting sun eye in normal
      infants without any obvious intracranial diseases. METHODS: A cross-sectional
      study was conducted in the Children's Hospital Medical Center in Tehran from June
      2001 to 2006. The study included 15 healthy infants who were referred to the
      neurosurgery clinic for setting sun eye. All were evaluated with brain imaging,
      and laboratory tests including at least thyroid function tests, and serum calcium
      and phosphorus. The cases were followed by regular outpatient visits until the
      age of 2 years. RESULTS: They were 3-8 months old at the time of referring to the
      outpatient clinic. Setting sun eye was observed by the mother in all cases and
      confirmed during their visit to the clinic. All had normal brain imaging and
      normal laboratory tests (thyroid function and electrolytes). Setting sun eye
      disappeared gradually during the follow-up period with a range of 2-8 months
      after detection by the mother. CONCLUSION: Despite the fact that setting sun eye
      is a grave sign, most commonly accompanied by other neurological signs and
      symptoms suggesting serious diseases, it might be observed as a sole finding in a
      totally normal infant with inconclusive brain imaging and laboratory tests. We
      found that this type of setting sun eye has a benign course and will disappear
      without any intervention several months after its detection (commonly before the
      age of 2 years without any intervention).

PMID- 18334842
TI  - Diagnosis and management of large occipitocervical cephaloceles: a 10-year
      experience.
AB  - BACKGROUND/AIMS: Cephaloceles are common malformations of the central nervous
      system. However, the great majority of clinical experiences in large
      occipitocervical cephaloceles have not been reported previously. The purpose of
      this report is to investigate the pathogenetic factors involved in the
      development of cranial dysraphism and to analyze the clinical and pathological
      factors that influence the outcome in patients. METHODS: Three hundred and twenty
      infants with craniospinal dysraphism and 12 with large occipitocervical
      cephaloceles were admitted to our institution in a 10-year interval between 1995
      and 2005. Infants with cephaloceles, including newborns and 5 within the first
      year of life, were all operated by two authors in our institution, and they were
      analyzed retrospectively. RESULTS: The sex predilection was limited to
      occipitocervical cephaloceles, where 8 of the 12 cases were females.
      Hydrocephalus was present in 25% of the patients at the time of diagnosis.
      Clinical presentation was most often consistent with hydrocephalus, focal
      neurological findings being a less prominent feature. Associated congenital
      anomalies were present in 50% of the children. Contemporary neuroimaging
      techniques including computed tomography and magnetic resonance imaging
      facilitated the diagnosis. Patients were initially managed by posterior fossa or
      cervical region exploration, followed by sac excision. Three cases died in the
      early postoperative period, and the surgical mortality in this series was 25%.
      They were the ones with the largest encephaloceles and microcephaly. The mean
      follow-up time was 3.4 years. The overall mortality rate for the whole series was
      33.3% (4/12). The size of the cephaloceles and the presence or absence of neural
      tissue in the sac largely determines the outcome for patients with
      occipitocervical cephaloceles. CONCLUSION: Infants with lesions greater than 50
      mm in diameter, containing a significant amount of neural tissue, have an
      extremely poor prognosis, especially if associated with microcephaly.

PMID- 18334843
TI  - Surgery without assistance in newborns and infants with hydrocephalus and neural
      tube defects.
AB  - Standard neurosurgical procedures for hydrocephalus and open neural tube defects
      in newborns and infants under 6 months of age were performed by a single
      neurosurgeon on his own without the help of an assistant or scrub nurse. The
      objective of this study was to assess the outcome of these procedures in terms of
      operating time, the presence of bacterial infection, and wound healing. Between
      2001 and 2004, a total of 126 procedures were performed on 82 patients under 6
      months of age. We observed 1 bacterial and 2 fungal infections. Two infections
      had already been detected at the beginning of the surgical procedure in
      cerebrospinal fluid (CSF) specimens obtained from children with Candida
      ventriculitis. The other infection occurred after leakage of CSF from a
      myelomeningocele 10 days after initial surgery. Our study suggests that excellent
      results can be achieved in standard neurosurgical procedures without assistance
      even in high-risk newborns and infants if resource or other constraints require
      such an unconventional approach.

PMID- 18334844
TI  - Head injury in children due to cricket ball scenario in developing countries.
AB  - OBJECTIVES: The aim of the study was the assessment of head injury caused by
      cricket ball injury in children. In underdeveloped countries, this is
      particularly important due to the absence of safety precautions. The study was
      undertaken to increase the public awareness of the need to reduce the morbidity
      related to this sport. METHODS: This was a prospective study in which all the
      children <18 years who had sustained head injury due to cricket balls were
      enrolled. RESULTS: The study included 27 children, 26 males and 1 female. Out of
      these 21 cases of head injury were due to hard plastic cricket balls and the rest
      were due to conventional cricket balls. In 25 patients, CT scan was done, which
      revealed a lesion in 21 of them. Six patients required surgery, 3 for extradural
      hematoma, 1 for acute subdural hematoma, 1 for contusion and 1 for compound
      depressed fracture. One death occurred in our series. There was no significant
      difference in the nature of injury sustained by either plastic or conventional
      cricket balls. CONCLUSION: Head injury due to cricket balls can lead to serious
      consequences even if an innocuous plastic ball is used in place of a conventional
      cricket ball. Public awareness apart from safety measures is required so that
      helmets are worn during playing. Change in the nature of the balls may bring a
      reduction in the severity of head injury.

PMID- 18334845
TI  - Unusual case of leptomeningeal dissemination of a diffuse pontine high-grade
      astrocytoma in a child.
AB  - A 12-year-old girl was seen in our hospital and diagnosed with diffuse pontine
      glioma. Treatment with radiotherapy was suggested, but the parents rejected this
      plan and took the child to another hospital where partial resection of the tumor
      was performed. The histological diagnosis was anaplastic astrocytoma. Returning
      to our hospital, the parents agreed to radiotherapy which was given in a total
      dose of 54 Gy. However, 3 months after completion of radiotherapy, the child
      developed widespread leptomeningeal dissemination of her disease and died 12
      months after the initial diagnosis. Since no effective curative methods of
      treatment exist for patients with diffuse pontine gliomas and surgical
      intervention is obsolete in this situation and may facilitate leptomeningeal
      dissemination of the disease, further innovative methods of treatment are needed
      to improve the bleak prognosis of these patients.

PMID- 18334846
TI  - Gliomatosis cerebri--an uncommon neuroepithelial tumor in children with
      oligodendroglial phenotype.
AB  - Gliomatosis cerebri(GC) is a highly aggressive, rare form of neuroepithelial
      tumor. Due to the diffuse nature of the tumor, its pathological grade is not
      conclusively established unless a biopsy is carried out from multiple sites. The
      tumor typically infiltrates the cortex in the subpial plane and also insinuates
      in the perineuronal space and around the Virchow-Robin spaces with relative
      preservation of the underlying brain parenchyma. Most of the previously reported
      cases of GC are astrocytic in nature. In this study, we report 2 pediatric
      patients of GC with oligodendroglial morphology on histopathological examination.
      In view of the rarity of the oligodendroglial phenotype of gliomatosis cerebri as
      well as the rare occurrence in children, we report these 2 cases.

PMID- 18334847
TI  - Sensitivity of mesenchymal stem cells and their progeny to medicines used for the
      treatment of hematoproliferative diseases.
AB  - BACKGROUND/AIMS: The influence of cytostatic medicines on mesenchymal stem cells
      (MSC) and their progeny, fibroblastic colony-forming units (CFU-F), was
      investigated. METHODS: Mice were treated with busulfan, cyclophosphamide,
      cytarabine, methotrexate and bortezomib, as used in clinical practice. MSC and
      CFU-F were analyzed 3 days and 6 weeks after the treatment termination. To
      estimate MSC numbers, the ectopic foci formation method was used. Briefly, a
      donor bone marrow plug was transplanted under the renal capsule of a syngeneic
      animal, leading to ectopic foci formation. The systemic response of the
      hematopoietic microenvironment to these drugs was studied using the same method
      applied to recipients pretreated with the medicines. RESULTS: CFU-F concentration
      was halved in the bone marrow of mice treated with busulfan, methotrexate and
      cyclophosphamide, and was not restored for the next 6 weeks. Proliferative
      potential and differentiation abilities of MSC were not affected by these
      medicines. The enlargement of foci size in mice treated with cytostatic agents
      was not conditioned by MSC, but by more mature stromal precursor cells.
      CONCLUSIONS: Cytostatic medicines affect stromal precursors in 2 ways: they
      decrease CFU-F concentration in the 'steady-state' bone marrow, while stimulating
      growth of the stromal microenvironment during its de novo formation. MSC are not
      sensitive to the cytostatic agents used.

PMID- 18334848
TI  - The effectiveness of voice therapy for teachers with dysphonia.
AB  - OBJECTIVE: An incorrect voice emission is a risk factor for developing
      occupational voice disorders. The study aimed at assessing the effectiveness of
      voice therapy in female teachers with dysphonia. METHODS: The study comprised 133
      subjects with voice disorders, taking part in a vocal training programme. A
      reference group for the present study included 53 teachers with dysphonia.
      Questionnaire surveys, phoniatric examination and videostroboscopic evaluation
      were conducted at initial and control examination. RESULTS: In the study group,
      an improvement after the vocal training was noted in most of the reported
      symptoms and also in some quantitative parameters of phoniatric examinations
      compared to the findings for the reference group. The number of patients who
      assessed their voice as normal increased significantly after the vocal training
      (2.3 vs. 46.6%). A significant increase in the mean maximum phonation time, from
      13.3 to 16.6 s, was observed. The same applied to voice frequency range (increase
      from 171 to 226.8 Hz). CONCLUSIONS: The outcomes of vocal training, such as a
      subjective improvement of voice quality and an increase in the quantitative
      parameters (prolonged maximum phonation time, extended voice range) seem to be
      important parameters for monitoring the effectiveness of training in correct
      voice emission.

PMID- 18334849
TI  - Patient self-perceptions of swallowing difficulties as compared to expert ratings
      of videofluorographic studies.
AB  - BACKGROUND/AIMS: Research investigating the relationship between subjective and
      objective assessment of dysphagia in patients with various diagnoses has yielded
      conflicting results. The goal of this study is to investigate the reliability of
      patient self-perceptions of swallowing difficulties compared to expert ratings of
      videofluorographic studies considering three medical diagnostic categories:
      neurological disorders, structural deficits and general medical diagnoses.
      METHODS: One hundred and three patients who were referred for videofluorographic
      swallow evaluation were included in the study. Face-to-face interviews with
      patients were conducted before their videofluorographic studies. The correlation
      between patient self-perceptions and expert ratings of the videofluorographic
      studies was established by comparing the results of patients' self-reports with
      the results of the videofluorographic studies. RESULTS: The correlation between
      patient self-perceptions of swallowing difficulties and expert ratings of the
      videofluorographic studies varied greatly depending on the patients' medical
      diagnoses. The correlation was mild in patients with neurological disorders,
      moderate in patients with structural deficits and high in patients with general
      medical diagnoses. CONCLUSION: The results of this study demonstrated that
      patient self-perceptions of swallowing difficulties should be used as one of the
      criteria, but not the only one, in making referrals for further swallowing
      evaluation, especially in patients with neurological disorders.

PMID- 18334850
TI  - Progressive changes in hepatoma cells stably transfected with hepatitis B virus X
      gene.
AB  - OBJECTIVE: The aim of this study is to investigate the molecular mechanism of
      hepatocellular carcinoma (HCC) development induced by hepatitis B virus X protein
      (HBx). METHODS: We previously established a H7402-X cell line that constitutively
      expresses HBx protein. In the present study, H7402-X gene expression profiles and
      proteins were examined using cDNA microarrays and Western blot analysis.
      Apoptosis was induced by adriamycin in H7402-X cells. The transcriptional
      activities of NF-kappaB and AP-1 were examined using a luciferase reporter gene.
      RESULTS: The DNA expression profiles identified candidate genes showing aberrant
      expression in cells overexpressing HBx. Western blot analysis showed that cyclin
      D, cyclin E, survivin, Bcl-2, and PCNA were up-regulated, whereas p27 was down
      regulated in H7402-X cells. Treatment with RNAi targeting HBx mRNA led to the
      down-regulation of these genes. H7402-X cells were resistant to adriamycin
      induced apoptosis. Luciferase reporter gene analysis revealed that HBx induces
      the transcriptional activities of NF-kappaB and AP-1. CONCLUSION: Our data
      provide additional insight into cellular targets of HBx, which allows a better
      understanding of HBx function and the progressive changes during HBx-mediated
      hepatocarcinogenesis.

PMID- 18334851
TI  - Phase II study of a combination of irinotecan and S-1 in patients with advanced
      gastric cancer (OGSG0002).
AB  - BACKGROUND/AIMS: To investigate the efficacy and safety of the combination
      therapy of irinotecan (CPT-11) plus S-1 in patients with advanced gastric cancer
      at the dose recommended by a previous phase I study. METHODS: A total of 23
      patients received 80 mg/m(2) of CPT-11 on days 1 and 15, and S-1 at a dose level
      set on the basis of the body surface area (BSA): 40 (BSA <1.25 m(2)), 50 (BSA >
      or =1.25 to <1.5 m(2)) or 60 mg (BSA > or =1.5 m(2)) b.i.d. was given from days 1
      21. RESULTS: The overall response rate was 47.8% (11 of 23, 95% confidence
      interval, CI: 27.4-68.2%). The median time to progression (TTP) was 210 days (95%
      CI: 145-322 days) and the median survival time was 394 days (95% CI: 241-484
      days). The incidence of grade 3 or 4 hematological and non-hematological toxicity
      was 17.4 and 8.7%. The most common hematological toxicity was anemia and the most
      common non-hematological toxicity was diarrhea. CONCLUSION: The combination
      therapy of CPT-11 and S-1 provided prolonged TTP with low toxicity, and the
      results warrant a further phase III study to define the efficacy in improvement
      of survival in patients with advanced gastric cancer.

PMID- 18334852
TI  - Gene expression of fructosamine 3 kinase in patients with colorectal cancer.
AB  - OBJECTIVE: Spontaneous non-enzymatic reaction of protein amino groups with
      glucose and other reducing sugars, known as glycation or Maillard reaction, has
      long been considered irreversible and inevitably followed by slow conversion of
      fructosamines and advanced glycation end products. Instead, recent identification
      of fructosamine 3 kinase (FN3K) has unveiled that fructosamines can be
      physiologically repaired, so that the FN3K enzyme could be considered a new form
      of protein repair. METHODS: Thirty-one consecutive patients with colorectal
      cancer were enrolled in the study. FN3K gene expression was determined using
      quantitative RT-PCR. RESULTS: The mean level of FN3K gene expression was
      significantly lower in cancer tissue than in the corresponding normal colorectal
      mucosa, and FN3K gene was under-expressed most particularly in the tumours
      located on the left side of the colon. CONCLUSIONS: Low mRNA levels of this
      enzyme in colon cancer tissue with respect to normal surrounding mucosa suggests
      that neoplastic cells have lost a protective enzymatic system. Reduced FN3K gene
      expression may be important in the pathogenesis and progression of colorectal
      cancer.

PMID- 18334853
TI  - Phase II study of a 3-week schedule of irinotecan combined with cisplatin in
      previously untreated extensive-stage small-cell lung cancer.
AB  - BACKGROUND: Irinotecan has been introduced to improve the treatment of small-cell
      lung cancer (SCLC). We conducted a trial involving a 3-week schedule of
      irinotecan combined with cisplatin (IP) to validate the efficacy and toxicity of
      this regimen in patients with previously untreated extensive-stage SCLC (ES
      SCLC). PATIENTS AND METHODS: Twenty-eight patients with previously untreated ES
      SCLC were enrolled in the study between January 2003 and December 2005.
      Irinotecan 60 mg/m(2) was administered intravenously on days 1 and 8 in
      combination with cisplatin 60 mg/m(2) on day 1 every 21 days. RESULTS: Twenty
      eight patients were followed until July 2007. The median follow-up time was 15.6
      months. The actual dose intensities (DIs) of cisplatin and irinotecan were 97.7
      and 92.2%, respectively. Among the 28 ES-SCLC patients, the objective response
      rate was 89.3% (25 patients). The major grade 3/4 hematological toxicity was
      neutropenia (26.9% of cycles). Grade 3/4 non-hematological toxicities were rare.
      The median progression-free and overall survival times were 8.7 and 16.5 months,
      with a 1-year survival rate of 66.6% and 2-year survival rate of 22.2%.
      CONCLUSION: The 3-week schedule of IP was feasible and showed a high DI of
      irinotecan and decreased toxicity.

PMID- 18334854
TI  - Retinoid receptor alpha and Beta expression in serous ovarian tumors.
AB  - The expression of retinoid acid receptors alpha (RARalpha) and beta (RARbeta) and
      estrogen receptor alpha (ERalpha) was assessed by immunohistochemistry and
      Western blotting in normal ovaries, serous cystadenoma (n = 20), serous
      borderline (n = 14), and serous ovarian cancer (n = 47) and was correlated in
      cancer cases with stage, grade, progress-free survival (PFS), and survival.
      RARalpha was increasingly expressed in benign cystadenomas, borderline, and low
      stage and advanced-stage neoplasms (p < 0.001). In stage III, G3 serous
      carcinoma, increased RARalpha expression was an independent prognostic factor
      associated with lower chemoresponse to first-line chemotherapy (taxol and
      carboplatin) and shorter PFS (p < 0.002).RARbeta and ERalpha expression did not
      correlate with RARalpha tumor characteristics or PFS and survival.

PMID- 18334855
TI  - Review of the treatment of trigeminal neuralgia with gamma knife radiosurgery.
AB  - BACKGROUND: Trigeminal neuralgia is a debilitating condition caused by
      compression of the trigeminal nerve, ganglions, or divisions. Gamma knife
      radiosurgery has been increasingly used in the treatment of trigeminal neuralgia
      as a non-invasive alternative to microvascular decompression and rhizotomies.
      METHODS: We reviewed the medical literature regarding outcomes, time course, and
      prognostic factors for successful pain control in gamma knife radiosurgery. The
      dosimetry, target, complications of treatment, as well as perceived quality of
      life in treatment were also reviewed. RESULTS AND CONCLUSION: The growing body of
      literature suggests that the low rates of complications of gamma knife
      radiosurgery, coupled with the high success rates and patient satisfaction, allow
      it to be increasingly used as primary intervention for trigeminal neuralgia for
      appropriate patients.

PMID- 18334856
TI  - Clinical cases where lesion therapy was chosen over deep brain stimulation.
AB  - Deep brain stimulation (DBS) surgery has become the gold standard for treatment
      of select refractory cases of Parkinson disease and essential tremor. Despite the
      usefulness of DBS surgery in many cases, there remain situations where lesion
      therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable
      alternative to DBS. We reviewed the University of Florida Institutional Review
      Board-approved database for movement disorders surgery and identified 286 DBS
      leads placed in 189 patients as well as 4 additional patients who had lesion
      therapy. In these 4 cases we reviewed the clinical presentations that resulted in
      a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy
      represents a viable alternative and has several important advantages, including a
      decreased need for access to specialists and clinical follow-up, improved
      affordability, and a lower infection risk.

PMID- 18334857
TI  - Comparison of atlas- and magnetic-resonance-imaging-based stereotactic targeting
      of the subthalamic nucleus in the surgical treatment of Parkinson's disease.
AB  - AIMS: To assess the variability of the subthalamic nucleus (STN) size,
      orientation and target coordinates from direct visualization on high-resolution
      magnetic resonance (MR) images in patients undergoing surgical intervention for
      Parkinson's disease. METHODS: Sixty-six patients with Parkinson's disease were
      included in this study. The STN was visualized directly on high-resolution MR
      images, the size and orientation in both coronal and axial planes were recorded,
      as were the coordinates of the dorsolateral STN target in relation to the
      anterior-posterior commissural (AC-PC) line. The same STN target was defined in
      the Schaltenbrand atlas and atlas-based coordinates in proportion to the
      patient's AC-PC dimension were calculated. MR-imaging-based STN target
      coordinates were compared with the corresponding atlas-based coordinates.
      RESULTS: Marked variation of STN size and orientation was observed. A significant
      difference was demonstrated on comparing left- and right-sided x and y
      coordinates. The comparison between MR-imaging-based and atlas-derived target
      coordinates demonstrated a significant difference in all directions except the
      left y coordinate. CONCLUSIONS: This study demonstrates the substantial
      individual variability of STN size, orientation and target coordinates and a
      significant difference between target coordinates obtained by direct visual
      targeting on MR images and those obtained by indirect targeting based on atlases.

PMID- 18334858
TI  - Assessment of contact location in subthalamic stimulation for Parkinson's disease
      by co-registration of computed tomography images.
AB  - AIMS: To study the validity of a co-registration method for postimplantation
      computed tomography (CT) images for localizing the location of an intracranial
      deep brain stimulator. METHODS: Three-dimensional reconstruction images of
      postimplantation CTs were co-registered with preoperative CTs by stereotactic
      planning software and used to localize 18 leads in the subthalamic nuclei of 10
      patients with Parkinson's disease. Our conventional method using superimposition
      of sagittal postimplantation magnetic resonance (MR) images were employed as a
      comparison. RESULTS: The co-registered CT images separately visualized four
      individual contacts; on the other hand, the MR superimposition method
      demonstrated the leads as a group of no MR signal areas. Although laterality of
      the distal contact did not differ between two methods, the distal contact was
      located more anteriorly and inferiorly by the MR superimposition method than by
      the CT co-registration method. CONCLUSION: The CT co-registration method is
      superior to MR in visualizing deep brain stimulation contacts and resolves
      problems of MR safety in patients treated with a neurostimulator.

PMID- 18334859
TI  - Ventral intermediate thalamic stimulation in complex tremor syndromes.
AB  - BACKGROUND/AIMS: We report on deep brain stimulation (DBS) in the ventral
      intermediate part of the thalamus in 4 patients with complex tremor syndromes, 2
      classified as Holmes tremor (HT) and 2 as thalamic tremor (TT). RESULTS: Three
      out of 4 patients showed intraoperative improvement and underwent DBS
      implantation. One patient with TT without intraoperative improvement was not
      provided with an implant. A sustained beneficial effect was present after a
      follow-up ranging from 20 months to 7 years, although there was partial
      persistence of the intentional tremor and of proximal myoclonic-dystonic
      movements. The mean global clinical impression score was 2. In 1 HT patient the
      benefit persisted after battery failure. CONCLUSION: The study confirms that
      ventral intermediate thalamic DBS can provide long-term efficacy for HT and TT.
      While the patients experienced considerable and lasting functional improvement,
      the effect was incomplete and not all elements of their complex movement
      disorders were equally suppressed.

PMID- 18334860
TI  - Direct localization of subthalamic nucleus supplemented by single-track
      electrophysiological guidance in deep brain stimulation lead implantation:
      techniques and clinical results.
AB  - BACKGROUND/AIMS: In subthalamic nucleus (STN) deep brain stimulation (DBS) lead
      implantation, it is still controversial whether it is more appropriate to employ
      indirect or direct methods in magnetic resonance imaging (MRI)-based tentative
      targeting and to select single- or multiple-track recording in
      electrophysiological definitive targeting. The efficacy of single-track
      electrophysiological recording through direct targeting was compared with the
      conventional indirect targeting methods in light of the identified STN thickness
      and clinical results. METHODS: The identified mean STN thickness, pre- and 6
      month postoperative Unified Parkinson's Disease Rating Scale (UPDRS), dose change
      of L-dopa and dopaminergic agonists were compared in indirect (midcommissural
      point-based, 44 procedures) and direct (image-based, 44 procedures) targeting
      methods. RESULTS: The identified mean STN thickness was significantly greater in
      the group employing direct methods. For evaluation of the UPDRS, a significant
      scale improvement was noted in part 2 OFF for both groups. Significant scale
      improvements occurred in parts 3 and 4 in the group employing the direct method.
      Both groups revealed significant L-dopa dose reduction with the tendency towards
      a greater reduction in the group employing the direct method. CONCLUSION: MRI
      based direct targeting supplemented by single-track recording could be justified
      as a standard for DBS lead implantation to achieve better clinical results.

PMID- 18334861
TI  - Long-term chronic stimulation of internal capsule in poststroke pain and
      spasticity. Case report, long-term results and review of the literature.
AB  - This report describes the long-term follow-up of chronic stimulation of the
      posterior limb of the internal capsule (IC) adjacent to the sensory thalamus in
      an elderly patient who suffered pain and spasticity in the left leg due to
      stroke. Both pain and motor symptoms ameliorated during 5 years of deep brain
      stimulation. Our case report suggests the possibility to stimulate a more precise
      representation of the inferior limbs within the IC and thalamus. We propose that
      chronic stimulation of the IC might be an effective surgical option to motor
      cortex stimulation when the pain and spasticity are referred to the lower limbs.

PMID- 18334862
TI  - An insight into the mechanistic role of Beclin 1 and its inhibition by
      prosurvival Bcl-2 family proteins.
AB  - A multiprotein complex composed of Beclin 1, PI(3)KC3 and UVRAG promotes
      autophagosome formation, while this activity is suppressed by a cohort of
      antiapoptotic Bcl-2 family members. Recently, we showed that a viral Bcl-2 of
      murine gamma-herpesvirus 68, known as M11, binds to Beclin 1 with markedly high
      affinity in comparison with cellular Bcl-2 or Bcl-X(L) that interacts with Beclin
      1 weakly.(1) Furthermore, the binding affinity directly correlated with the
      potency of inhibition of autophagosome formation in cells. Herein, we present
      additional data showing that Beclin 1 forms a large homo-oligomer, and this
      oligomerization is partly disrupted by the binding of M11. Oligomerized Beclin 1
      is proposed to serve as a platform enabling a concerted action of many molecules
      of the associating proteins, including Bif-1 that could be directly involved in
      autophagosome biogenesis on membranes owing to its BAR domain.

PMID- 18334863
TI  - Transporter pumps and imatinib: a cause of pharmacokinetic resistance?

PMID- 18334865
TI  - Issues to consider in cognitive-behavioural therapy for irritable bowel syndrome.
AB  - [table: see text] Physical, psychological and social factors interact in IBS.
      Evidence for the efficacy of CBT in its management is available. The cognitive
      behavioural model can also be used to inform medical care for IBS. In designing
      and evaluating a cognitive-behavioural intervention, it is important to consider
      the particular strategies included, the goals being worked towards, the selection
      of patients to whom the intervention is offered and how far it is tailored to
      their needs. Other important factors are the skills of the therapist, the setting
      in which therapy is delivered and whether it is offered together with medication.

PMID- 18334866
TI  - Is acid relevant in the genesis of dyspeptic symptoms associated with nonerosive
      reflux disease?
AB  - [table: see text] A consistent subset of patients with NERD suffers from symptoms
      centered in the upper part of the abdomen that are more characteristic of
      functional dyspepsia than reflux disease. The cause of this overlap is still
      unclear, but acid has been implicated as one of the possible common
      pathophysiological factors responsible for these two categories of upper
      gastrointestinal (GI) symptoms. Many physiological investigations and the modest
      success of proton pump inhibitors in resolving dyspeptic symptoms associated with
      typical reflux syndrome seem to support the concept that functional dyspepsia and
      NERD are two separate entities, which need to be treated with different drugs.

PMID- 18334867
TI  - Cost-effectiveness of cognitive behaviour therapy in addition to mebeverine for
      irritable bowel syndrome.
AB  - OBJECTIVES: Irritable bowel syndrome is often treated in primary-care settings,
      and it has a relatively large economic impact. Cognitive behaviour therapy (CBT)
      in addition to mebeverine has been shown to be effective in the short term,
      compared with treatment with mebeverine alone. This study assesses the impact
      that CBT in addition to mebeverine has on resource use, and its cost
      effectiveness. METHODS: Participants were recruited from general practices: those
      with ongoing symptoms were randomly allocated either to remain just on mebeverine
      or to receive CBT in addition to mebeverine. Service use and lost employment were
      measured at baseline and at the 3-month, 6-month and 12-month follow-ups. The net
      benefit approach was used for combining the data on therapy costs and symptoms.
      RESULTS: The mean additional cost of CBT was pound 308. No significant impact of
      CBT on the use of other services or on lost employment was noted. The cost per
      clinically important reduction in symptoms was pound 220 by the end of treatment,
      pound 171 at the 3-month follow-up, pound 1027 at the 6-month follow-up and pound
      3080 at the 12-month follow-up, for CBT in addition to mebeverine compared with
      mebeverine alone. CONCLUSIONS: CBT in addition to mebeverine seems to have
      reasonable cost-effectiveness in the short-term treatment of irritable bowel
      syndrome, but not beyond 3 months.

PMID- 18334868
TI  - Correlation between oesophageal acid exposure and dyspeptic symptoms in patients
      with nonerosive reflux disease.
AB  - BACKGROUND & AIMS: Oesophageal acidification induces dyspeptic symptoms in
      healthy individuals. This study aimed to evaluate the correlation between
      oesophageal acid exposure and dyspeptic symptoms in patients with nonerosive
      reflux disease. METHODS: A total of 68 patients with dominant symptoms of
      heartburn, negative upper gastrointestinal endoscopy and concomitant dyspeptic
      symptoms participated in the study. The severity of dyspepsia and reflux-related
      symptoms was evaluated, and 24-h gastro-oesophageal pH-monitoring study was
      performed in all patients at baseline and after 4 weeks of therapy with
      esomeprazole 40 mg. RESULTS: Oesophageal basal acid exposure was pathological in
      43 patients and normal in 25 patients, with a similar prevalence and severity of
      individual dyspeptic symptoms in the two groups. A significant correlation
      between reflux and dyspepsia scores was observed in the subgroup of patients with
      normal, but not in those with abnormal pHmetry (r=0.4, P=0.04 and r=0.2 P=0.07,
      respectively). After esomeprazole, a reduction in severity of dyspepsia (>or=50%
      with respect to baseline) was observed, independent of improvement of reflux
      associated symptoms. Improvement in dyspepsia was, however, similar in patients
      with normal and abnormal basal acid exposure (14/25 vs. 33/43, respectively,
      P=NS). CONCLUSION: Dyspeptic symptoms coexist in a subset of nonerosive reflux
      disease patients, but prevalence and severity of the symptoms seems to be
      independent of oesophageal acid exposure.

PMID- 18334869
TI  - Healthcare seeking in gastro-oesophageal reflux disease: a qualitative study.
AB  - BACKGROUND: Gastro-oesophageal reflux disease (GORD) is a common problem in the
      community, and many patients do not seek medical attention despite potential
      morbidity and the availability of effective therapeutic interventions. The
      factors which determine healthcare seeking in GORD are not well understood. AIM:
      To examine the symptom experience and health and illness beliefs in people with
      GORD, who had either been diagnosed with the condition, or were dealing with the
      symptoms themselves. METHODS: A total of 12 focus groups and 65 face-to-face
      interviews were conducted in the USA, UK, France and Germany, and involved 164
      participants, who had either been diagnosed with GORD or were identified as
      having GORD in the community, using a random digit dialling telephone method.
      Transcripts of focus groups and interviews were analysed thematically, using a
      constant comparative approach, to identify key factors associated with healthcare
      seeking. RESULTS: Patients' descriptions of GORD symptoms were often vivid, with
      the use of unexpected imagery and unusual beliefs about causality. We were able
      to identify four factors associated with healthcare seeking for GORD which were:
      the characteristics of symptoms (intensity and control), the perceived
      seriousness of symptoms, interference by symptoms with daily life and views about
      medicines and the medical profession. CONCLUSION: Patients with GORD, using both
      self care and formal medical care, have a surprising range of ideas about the
      causes and best treatments of their symptoms. Physicians' awareness of these
      beliefs, coupled with an understanding of the factors associated with healthcare
      seeking for GORD, is likely to be important in enhancing clinical management and
      in patient and public education.

PMID- 18334870
TI  - Human leucocyte antigen and TNFalpha polymorphism association in microscopic
      colitis.
AB  - OBJECTIVES: Coeliac disease (CD) is common in patients with microscopic colitis
      (MC). The human leucocyte antigen (HLA)-DR3-DQ2 haplotype is strongly associated
      with CD, and there is evidence for an association with MC. We analysed the
      genetic background of MC by assessing the haplotypes of HLA-DR3-DQ2 and HLA-DR4
      DQ8. In addition, TNFalpha gene polymorphism (-308) associated with
      susceptibility to several autoimmune diseases was studied. METHODS: Eighty
      patients with MC including 29 with collagenous colitis (CC) and 51 with
      lymphocytic colitis (LC) were typed for HLA-DR3-DQ2, and HLA-DR4-DQ8 molecule
      encoding genes using either an allele-specific PCR, or hybridization with
      sequence-specific oligonucleotides. Duodenal biopsies (N=78) confirmed the
      diagnosis of CD in 15 (18.8%) patients. TNFalpha(308) alleles were analyzed in 78
      patients with MC (27 with CC and 51 with LC). A control group of 3627 patients
      was used in the HLA study and 178 patients in the TNFalpha study. RESULTS: HLA
      DR3-DQ2 haplotype was more frequent in patients with MC (43.8%) including both
      subgroups (LC, 44.8%; CC, 43.1%; P<0.001), and MC with CD (86.7%; P<0.001) and
      without CD (33.3%; P=0.003), compared with the controls (18.1%). Similarly, the
      TNF2 carrier rate was higher in MC (46.2%; P<0.001) including both CC (44.4%;
      P=0.031) and LC (47.1%; P=0.001), and both MC patients with CD (66.7%; P=0.001)
      and without CD (39.3%; P=0.019), compared with the controls (23%). CONCLUSION:
      Both CC and LC are associated with the HLA-DR3-DQ2 haplotype and with TNF2 allele
      carriage. These associations are present also in MC patients without CD. The
      shared predisposing HLA-DR3-DQ2 haplotype and the high prevalence of CD in
      patients with MC suggest an epidemiological overlap, and probably some
      similarities in the pathogenesis of CD and MC.

PMID- 18334871
TI  - Platelet-leucocyte aggregates form in the mesenteric vasculature in patients with
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: Inflammation and thrombosis are closely related processes,
      which may play a role in the pathogenesis, as well as complications, of
      inflammatory bowel disease (IBD). Platelet activation and platelet-leucocyte
      aggregation are increased and platelet aggregation is known to occur in the
      mesenteric vasculature in IBD. The aims of this study were to test the hypotheses
      that platelet-leucocyte aggregation, platelet activation and neutrophil
      activation occur in the mesenteric vessels of patients with ulcerative colitis
      (UC). PATIENTS AND METHODS: Platelet-leucocyte aggregates (PLAs), platelet
      activation (P-selectin expression) and neutrophil activation (L-selectin
      expression, which decreases on neutrophil activation) were assessed flow
      cytometrically in mesenteric arterial, and venous blood sampled in eight patients
      with UC and eight controls with colonic carcinoma undergoing intestinal
      resections. RESULTS: In the patients with UC, the number of PLAs in the
      mesenteric vein exceeded that in the artery, the median rise being 38% (P=0.02).
      In UC, arterial PLA numbers were 0.17 (0.02-0.32) (median, range) x 10(9)/l
      versus venous 0.26 (0.09-1.6) x 10(9)/l (P=0.02). The median percentage increase
      was 45%. Mesenteric PLA formation did not occur in patients with colonic
      carcinoma [arterial 0.06 (0.03-0.49) x 10(9)/l vs. venous 0.05 (0.02-0.35) x
      10(9)/l; P=0.55]. The median percentage change was +45% for UC patients and -5%
      for controls. No arteriovenous gradient was observed in P-selectin expression,
      but L-selectin expression (arbitrary units), increased in the mesenteric
      vasculature of the UC patients [arterial 839 (503-995), venous 879 (477-1035);
      P=0.03] and fell in those with colonic carcinoma [arterial 900 (660-959), venous
      850 (546-957); P=0.04]. The median percentage change was +4% for UC and -7% for
      controls. CONCLUSION: The finding of increased numbers of PLAs in the venous
      mesenteric circulation supports the hypothesis that activated vascular
      endothelium stimulates PLA formation in UC.

PMID- 18334872
TI  - Real-time PCR quantification analysis of five mucosal transcripts in patients
      with Crohn's disease.
AB  - OBJECTIVES: Crohn's disease has a genetic background. Onset of the clinical
      manifestations, however, is suggested to be triggered by environmental factors.
      Microarray analysis has shown that the expression of transcripts aldolase B,
      elafin, MST-1, simNIPhom and SLC6A14 are altered in patients with ulcerative
      colitis. The primary aim of this study was to explore the expressions of these
      five transcripts in macroscopically inflamed and noninflamed mucosa in patients
      with Crohn's disease. METHODS: Mucosal specimens obtained from colon in
      consecutive patients with Crohn's disease (n=23) and controls (n=67) undergoing
      colonoscopy were analyzed using real-time PCR technique. RESULTS: The expressions
      of the transcripts aldolase B, elafin, simNIPhom and SLC6A14 were increased,
      whereas the expression of MST-1 was decreased in noninflamed rectal mucosa in
      patients with Crohn's disease compared with controls. The expression of aldolase
      B was increased and the expressions of elafin and simNIPhom were decreased in
      inflamed colonic mucosa compared with noninflamed rectal mucosa in patients with
      Crohn's disease. No correlation, between the clinical activity of Crohn's disease
      (Mayo score <or=5 vs. >or=6) and transcript expression was detected. CONCLUSION:
      The mucosal transcript pattern in Crohn's disease may, based on the known
      biological function of the transcripts, explain some of the typical features of
      Crohn's disease and indicate a possible pathophysiological role of microbes. Our
      results may thereby contribute to the understanding of the pathogenesis and
      manifestations of Crohn's disease.

PMID- 18334873
TI  - Cancer in patients with ulcerative colitis, Crohn's disease and coeliac disease:
      record linkage study.
AB  - OBJECTIVE: The objective of this study was to determine the risk of cancers in
      cohorts of patients with ulcerative colitis, Crohn's disease, or coeliac disease,
      compared with the risk in a control cohort. METHOD: The method used was the
      analysis of a linked statistical database of hospital and mortality data in an
      area in southern England. RESULTS: Rate ratios for cancer (excluding cases
      occurring within the first year of follow-up), compared with the value of 1 in
      the control cohort, were 1.25 [95% confidence interval (CI), 1.13-1.39] in
      patients with ulcerative colitis, 1.27 (95% CI, 1.11-1.45) with Crohn's disease,
      and 1.16 (95% CI, 0.94-1.43) with coeliac disease. In patients with ulcerative
      colitis or Crohn's disease, there was a significantly high risk of cancer of the
      colon [2.22 (95% CI, 1.71-2.83) and 1.64 (95% CI, 1.09-2.39), respectively]. In
      patients with ulcerative colitis there was a significantly high risk of cancer of
      the rectum [1.84 (95% CI, 1.27-2.58)]. In patients with ulcerative colitis or
      Crohn's disease, who did not undergo partial or total colectomy for it, the rate
      ratios for colon cancer were, respectively, 5.52 (95% CI, 4.39-6.71) and 4.81
      (95% CI, 3.52-6.47). In ulcerative colitis, there was an elevated risk of cancer
      of the rectum, liver and ovary. The rate ratio for lung cancer was low, but of
      borderline significance [0.72 (95% CI, 0.50-0.98)]. In Crohn's disease, the rate
      ratio was high for cancer of the cervix [2.63 (95% CI, 1.12-5.29)]. In patients
      with coeliac disease, the high-risk cancer was non-Hodgkin's lymphoma [rate ratio
      3.28 (95% CI, 1.49-6.28)]. CONCLUSION: All three diseases carry an increased risk
      of cancer overall when the first year cases are included, though fairly modest in
      scale, and the increased risk seen in coeliac disease reduces when first year
      cases are excluded. Each has a distinctive pattern of individual high-risk
      cancers.

PMID- 18334874
TI  - Significantly elevated Helicobacter pylori density and different genotype
      distribution in erosions as compared with normal gastric biopsy specimen detected
      by quantitative real-time PCR.
AB  - BACKGROUND AND AIM: Determination of the local densities of Helicobacter pylori
      and its genotypic variations in gastric biopsy specimens by using novel real-time
      PCR-based methods could support the precise diagnosis and understanding of H.
      pylori infections. METHODS: Serial dilutions of H. pylori (0.016-16
      microg/microl), control, bacterial, and human DNA samples were prepared. Fresh
      frozen gastric biopsy specimens were taken from 103 patients, and the DNA was
      isolated. Quantitative determination of the ureaseA gene using hybridization
      probes with parallel evaluation of an internal human control gene (beta-globin)
      was performed by real-time PCR. CagA and VacA s1 genotypic characterizations were
      also performed. The data were compared with urea breath test (UBT), histology,
      and serological testing. RESULTS: The presence of H. pylori could be detected by
      ureaseA-fluorescence energy transfer (53%), UBT (51%), serological testing (48%),
      and histology (52%) when compared with the gold standard (54%). A significant
      correlation was found between the quantitative real-time ureaseA/beta-globin
      ratio-based H. pylori frequency and the UBT results (P<0.01). Significantly
      increased bacterial density was found in the erosions when compared with the
      healthy part of the antrum and corpus (P<0.01). Real-time PCR VacA s1 results
      were in significant correlation (P<0.01) with those of serological tests, but
      CagA results were not. The genomic profiles (VAC/GAC) were different in 13.7% of
      the cases, which involved three different locations in the stomach. CONCLUSION:
      Real-time PCR was the most reliable method for H. pylori diagnosis. Furthermore,
      quantification and genotyping could also be performed using this technique. The
      density of H. pylori was significantly increased in macroscopic erosions.

PMID- 18334875
TI  - Enhanced gastric IL-18 mRNA expression in Helicobacter pylori-infected children
      is associated with macrophage infiltration, IL-8, and IL-1 beta mRNA expression.
AB  - OBJECTIVE: To investigate IL-18 mRNA expression in the gastric mucosa in
      Helicobacter pylori-infected children and its association with macrophage
      infiltration, IL-8, and IL-1 beta mRNA expression. METHODS: From 39 children,
      blood samples were taken for IL-1 beta gene polymorphism analysis and antral
      biopsies were obtained for histology (including macrophage immunostaining),
      culture and semiquantitative analysis of IL-18, IL-8, IL-1 beta, and CD14 mRNA
      expression by reverse transcription-PCR (RT-PCR). RT-PCR was used for H. pylori
      ureA and cagA mRNA detection in gastric tissue. RESULTS: H. pylori-infected
      patients had significantly higher IL-18, IL-8, and IL-1 beta transcript levels
      and macrophage numbers in the antral mucosa than H. pylori-negative children. IL
      1 beta-511/31 gene polymorphism had no impact on gastric IL-1 beta mRNA levels.
      IL-18 mRNA expression correlated with mRNA expression of IL-8 and IL-1 beta, and
      transcript levels of all three cytokines were associated with macrophage
      infiltration and CD14 mRNA expression in the gastric tissue. Significant
      correlation was also observed between macrophage numbers and histological
      parameters of gastritis. CONCLUSION: These results suggest that interleukin(IL)
      18 and macrophages may have an important function in gastric inflammatory
      response to H. pylori infection in children. IL-18, and possibly CD14 receptor
      signalling pathway, may be involved in macrophage activation and subsequent IL-8
      and IL-1 beta release.

PMID- 18334876
TI  - Estimating the future health burden of chronic hepatitis B and the impact of
      therapy in Spain.
AB  - BACKGROUND: Chronic hepatitis B virus (HBV) infection can lead to fatal
      complications and death. Only a relatively small proportion of patients actually
      receive medication, and the majority requires long-term antiviral therapy that
      can result in the emergence of resistant strains of HBV. The study aimed to
      estimate the future burden of chronic hepatitis B in Spain over the next 20
      years, the impact of current lamivudine treatment and the emergence of drug
      resistant HBV. METHODS: We constructed a hypothetical cohort of people with
      active chronic HBV infection in Spain in 2005, and 'followed' the cohort for 20
      years. The cohort was stratified with respect to factors that affect prognosis
      (i.e. hepatitis B e-antigen and histology-defined status). To estimate the
      burden, Markov mathematical simulation was performed based on three scenarios:
      natural history, treatment with antiviral drug (lamivudine) and treatment with a
      hypothetical drug with identical profiles to lamivudine but to which there is no
      resistance. RESULTS: We estimated that in 2005 there were around 111,000
      individuals suffering from active chronic HBV infection. If the cohort is not
      treated, by the year 2025 there will be about 60,000 events of morbidity and
      40,000 cases of liver-related deaths, with 1.84 billion euro expected to be
      consumed in providing care for the cohort. Treating 35% of the cohort with
      lamivudine will reduce the morbidity and mortality by 19 and 15%, respectively;
      whereas the hypothetical drug will reduce the morbidity and mortality by 27 and
      24%. The cumulative cost savings resulting from the use of lamivudine and the
      hypothetical drug, respectively, are 160 and 300 million euro. Antiviral
      resistance accounts for a reduction of about one-third in the potential benefit
      of treatment, and almost a half of the potential cost saving. CONCLUSION: Chronic
      hepatitis B will pose a great burden in the future if the individuals with active
      disease are left untreated. Effective antiviral therapy and treatment coverage
      have substantial impact in reducing the future burden; however, antiviral
      resistance decreases treatment benefit considerably.

PMID- 18334877
TI  - Immune cells in primary gastrointestinal stromal tumors.
AB  - INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are the most common
      mesenchymal tumors of the gastrointestinal tract. They are regarded as having
      relatively uniform histology, although their potential for malignant behavior
      varies. Despite a strong promoting role of tumor-infiltrating innate immune cells
      in neoplastic progression, the presence of immune cells in GISTs has not yet been
      studied. METHODS: A total of 47 untreated, c-kit-positive primary GISTs were
      immunohistochemically analyzed to distinguish histiocytic and dendritic cells
      (DCs) (KIM-1P, fascin, and CD68) from cells of lymphoplasmacellular origin (CD3,
      CD20, and CD56). Furthermore, the gene expression of proinflammatory cytokines
      was characterized by real-time, reverse transcription-PCR analysis of total RNA
      extracted from frozen tissue samples. RESULTS: KIM-1P+ cells were the dominant
      immune cells (851+/-295 cells/mm2) and were scattered among the tumor cells. Most
      of the KIM-1P+ cells showed cellular projections characteristic of DCs. Fascin
      positivity identified a subgroup of DCs. In comparison to KIM-1P+ cells, there
      were significantly fewer CD68+ macrophages (196+/-217 cells/mm2). CD3+ T cells
      were the dominant lymphocytes (201+/-331 cells/mm2), whereas B cells (60+/-126
      cells/mm2) were few. On transcriptional level, a concomitant gene expression of
      cytokines for the classical acute phase cytokines TNF-alpha and IL-6 was missing,
      thus supporting the rather innate status of immune cells. CONCLUSION: GISTs
      contain, beside T lymphocytes, a high number of monocyte-derived cells, which we
      suggest are, at least in part, immature DCs. Together with the lack of gene
      expression of inflammatory cytokines in tumor tissue our results point to a
      possible 'symbiotic relationship' between the tumor and the local immune cells.

PMID- 18334878
TI  - Prevalence of gastrointestinal symptoms in patients with chronic obstructive
      pulmonary disease.
AB  - BACKGROUND: Symptoms of gastro-oesophageal reflux disease (GERD) have previously
      been shown to be of importance in patients with asthma. Limited data, however,
      exist on the prevalence of GERD in patients with chronic obstructive pulmonary
      disease (COPD), and information about the occurrence of the total burden of
      gastrointestinal (GI) symptoms in these patients is lacking. METHODS: A total of
      113 patients with COPD completed four self-administered questionnaires: the
      Gastrointestinal Symptom-Rating Scale (GSRS), ROME II modular questionnaires
      (criteria for irritable bowel syndrome), the Psychological General Well-Being
      index (PGWB), and the Hospital Anxiety and Depression scale. Eighty-two patients
      with chronic renal failure (CRF) and 2000 healthy individuals from the general
      Swedish population served as controls. RESULTS: The total GSRS score in patients
      with COPD was 2.12 (1.92-2.28) which was significantly higher than the score from
      the general population of 1.96 (1.81-2.12). No significant difference between
      COPD and CRF patients was, however, observed, in any of the GSRS dimensions.
      Patients in the COPD group had lower total PGWB scores compared both with CRF
      patients 90 (78-104) vs. 98 (83-113) (P<0.05) and with the general population 103
      (102-104) (P<0.001). A negative correlation between the GSRS and PGWB scores (r=
      0.49; P<0.001) was observed in patients with COPD. Sixteen (14%) of the patients
      with COPD fulfilled the Rome II criteria for irritable bowel syndrome.
      CONCLUSION: The prevalence of GI symptoms is higher in patients with COPD than in
      healthy individuals, but not higher than in CRF patients. The GI symptoms are
      associated with impairments in psychological well-being, and they require
      diagnostic workups to explore different treatment options in these patients.

PMID- 18334879
TI  - Prospective pilot evaluation of a new needle prototype for endoscopic
      ultrasonography-guided fine-needle aspiration: comparison of cytology and
      histology yield.
AB  - OBJECTIVES: Endoscopic ultrasonography (EUS) with the adjunct of EUS-guided fine
      needle aspiration has become an important diagnostic modality in
      gastroenterologic oncology. EUS-guided fine needle aspiration mainly relies on
      cytology; data are scarce that compare cytology and histology. While testing a 22
      gauge prototype needle, we prospectively compared the yield for both. METHODS:
      Forty-two consecutive patients (27 male, 15 female; mean age 59.2 years, range:
      17-90 years) were included. In each patient we aimed to make two needle passes,
      and if the material acquired appeared insufficient macroscopically (no in-room
      cytopathology was available), further passes were done. The material was sent for
      cytological and histological assessment. RESULTS: A median number of two passes
      (range: 2-3) were uneventfully performed for pancreatic lesions (n=30),
      mediastinal and other lymph nodes/masses (n=8) and various other lesions (n=4)
      and yielded adequate material for cytology, histology or at least one of the two
      investigations in 62, 67 and 74% of patients, respectively. No false positive
      results were found (specificity 100%). Sensitivities were 58.6 and 65.5%,
      respectively, for cytology and histology alone; combined assessment increased
      sensitivity to 79.3%. When adjusted values were calculated, based only on those
      cases with adequate material, sensitivity was 89.5% for cytology and 85.7% for
      histology, and increased to 100% with combined assessment. CONCLUSION: The new
      needle achieves sensitivities similar to those previously reported with no
      significant differences in sensitivity between cytology and histology. More
      effective tissue acquisition methods must be sought to improve overall results.

PMID- 18334880
TI  - Unusual manifestation of brucellosis: liver abscess and pancytopenia caused by
      Brucella melitensis.
AB  - Brucellosis is a zoonosis with a worldwide distribution, and still endemic in
      Greece. Although hepatic involvement is common, cholecystitis and hepatic
      abscesses represent rare complications of the disease. Hematological
      manifestations of brucellosis include various abnormalities such as anemia and
      leucopenia, but the disease rarely presents with pancytopenia. We present a case
      of liver abscess and pancytopenia caused by Brucella melitensis in a 54-year-old
      worker who consumed unpasteurized dairy products. The patient was admitted twice
      to our hospital and finally diagnosed as suffering from a gallbladder empyema
      complicated by a liver abscess, for which he underwent surgery. Blood cultures
      drawn on his second admission isolated Brucella melitensis. Repeated serum
      agglutination testing for brucella turned out negative.

PMID- 18334881
TI  - Diagnosis of megacystis-microcolon intestinal hypoperistalsis syndrome with
      aplastic desmosis in adulthood: a case report.
AB  - Megacystis-microcolon intestinal hypoperistalsis syndrome (MMHIS or Berdon
      syndrome) is an autosomal-recessive disorder characterized by chronic intestinal
      obstruction. Although the disease is often diagnosed in female infants we
      describe a man with late diagnosis in adulthood. Our patient presented soon after
      birth with intestinal obstruction and developed short bowel syndrome after
      multiple intestinal resections. Of note, the connective tissue net within the
      muscle layers of the intestinal wall was absent ('aplastic desmosis'). This case
      illustrates the variable clinical features of MMHIS and aplastic desmosis, which
      might delay the correct diagnosis of a severe disorder.

PMID- 18334882
TI  - Symptomatic hypocalcemia after sodium phosphate preparation in an adult with
      asymptomatic hypoparathyroidism.
AB  - Sodium phosphate is widely used as a bowel cleansing preparation. Its use is,
      however, not without risk. It can induce serious adverse effects like
      hypocalcemia, hyperphosphatemia and renal failure. In this case, a 75-year-old
      woman without known contraindications developed hypocalcemic tetany,
      hyperphosphatemia and renal failure after oral sodium phosphate. Asymptomatic
      hypoparathyroidism owing to previous thyroid surgery was identified as a new
      contributing risk factor for this complication.

PMID- 18334884
TI  - Liver disease in pregnancy and its influence on maternal and fetal mortality: a
      prospective study from Chennai, Southern India.

PMID- 18334883
TI  - Ciliated hepatic foregut cyst discovered after kidney transplantation in a
      hepatitis C virus-infected patient: a report of one case and review of the
      literature.
AB  - Ciliated hepatic foregut cyst (CHFC) is a rare liver lesion derived from the
      embryonic foregut. In most cases, CHFC remains asymptomatic but some malignant
      transformations have been reported. Typical imaging features usually lead to
      diagnosis using ultrasonography, computed tomography scan examination or MRI.
      When the diagnosis remains uncertain, a fine needle aspiration with cytology is
      appropriate. The presence of ciliated epithelial cells with hepatocytes and
      mucous cells on aspiration cytology is enough to assess the diagnosis. Surgery is
      recommended when there is uncertain diagnosis or malignant lesion suspicion. We
      report herein, the case of a CHFC discovered in a hepatitis C virus-infected
      patient following a renal transplantation. To eliminate a lymphoma or a liver
      tumor arising because of patient's immunosuppression status, a surgical resection
      of the lesion was performed. The surgical outcome was uneventful. Regarding this
      case, embryogenesis, morphological characteristics and treatment of the lesions
      are discussed.

PMID- 18334885
TI  - Acute hepatitis following assumption of a herbal remedy.

PMID- 18334886
TI  - Chlamydia infection as risk factor for pediatric biliary tract disease.

PMID- 18334887
TI  - Right ventricular outflow tract reconstruction: valved conduit of choice and
      clinical outcomes.
AB  - BACKGROUND: The valved conduit of choice in right ventricular outflow tract
      (RVOT) reconstruction provides a challenge for cardiac surgeons. The present
      study collected data regarding the clinical outcome of valved conduits for RVOT
      reconstruction, so as to explore various options of ideal conduits in clinical
      practice. METHODS: English language articles on valved conduits for RVOT
      reconstruction were retrieved from the MEDLINE database with respect to the
      commonly used homograft, stented xenograft and stentless xenograft, and the
      occasionally used autologous tissue valved conduit as well. Clinical outcomes of
      each conduit were outlined with respect to their early and late mortalities,
      conduit failure, conduit reoperation, reoperation-free interval, actuarial
      freedom from reoperation, and survival rates. Conduit-related complications, risk
      factors and pathological findings of the valved conduits were summarized.
      RESULTS: Conduit failure was defined as the need for reoperation for conduit
      stenosis or extrinsic compression, conduit regurgitation, or anastomotic
      dehiscence. The conduit failure rates at 2 years were 9-55%, 35% and 25% for
      homograft, stented xenograft and stentless xenograft conduits, respectively. The
      5-year actuarial freedoms from reoperation were 87-98.2% for homograft, 37% for
      Hancock, 81-92% for Carpentier-Edwards, 78% for Contegra, and 82.95% for LabCor,
      respectively. The result for Hancock at 5 years appeared to be disappointing,
      although it did prove promising, and was 79.5% at 10 years and 65.8% at 15 years.
      Autologous pericardial valved conduits for RVOT reconstruction showed superb
      properties, and the autologous monocusp pulmonary artery conduit functioned well
      early postoperatively, but data for long-term follow-up are lacking. CONCLUSION:
      Conduit failure and explant is inevitable. This phenomenon is worse with a longer
      follow-up. Mechanisms involved in conduit failure are unknown, even though they
      were accounted for by calcification and extensive intimal proliferation, and
      somatic outgrowth. Homografts are commonly used and have experienced a long
      history. The pulmonary homograft is the most commonly used RVOT conduit,
      especially in small children, due to its excellent characteristics. The newly
      developed Contegra conduit has become popular due to its availability in full
      sizes and the acceptable results obtained at intermediate follow-up. The Hancock
      conduit can function sufficiently well for as long as 5-10 years, and early valve
      failure is relatively rare. It is admissible to use the Hancock conduit as an
      interim measure for future conduit reoperation due to its adequate function until
      subsequent operation. The application of an autologeous tissue valved conduit
      should be considered when other alternatives are not available.

PMID- 18334888
TI  - Cardiopulmonary bypass as an adjunct for the noncardiac surgeon.
AB  - The use of cardiopulmonary bypass (CPB) in noncardiac surgical settings has been
      increasingly developed and has greatly benefited noncardiac surgeon. A few years
      after the advent of CPB as well as profound hypothermic circulatory arrest in the
      early years, it was employed by neurosurgeons in cerebrovascular surgery and by
      general thoracic surgeons in carinal tumor resection. Indications for CPB were
      extended and modified year after year. It has facilitated not only the surgical
      management by surgeons of lesions that cannot be managed safely and effectively
      by conventional techniques, or conventional techniques carry significant risks to
      the patient, but also the preservation of the viability of multiple organ
      procurement, the practice of isolated limb perfusion for the treatment of
      malignancies of the extremities, and emergent cardiopulmonary resuscitation.
      Owing to the complications arising from CPB and profound hypothermic circulatory
      arrest, such as postoperative bleeding, coagulopathy, and neurologic deficits,
      efforts have been made to avoid these common hazards. Thus, innovative techniques
      including extracorporeal membrane oxygenation, percutaneous cardiopulmonary
      support, venovenous bypass, normothermic CPB, and minimally invasive approaches
      have emerged and played an important role as alternatives of standard CPB in
      decreasing morbidity and mortality and improving survival.

PMID- 18334889
TI  - Is there an association between depression and cardiovascular mortality or sudden
      death?
AB  - The results of many studies and recent meta-analyses strongly suggest that
      depression is a risk factor for total and cardiovascular mortality, both in the
      general population and in patients with known heart disease. By contrast, the
      association between depression and sudden death or cardiac arrest has received
      little attention. This issue has been investigated in three recent studies; two
      were carried out in the general population and showed depression to be a
      independent risk factor for sudden death. The other study was carried out in
      patients with acute myocardial infarction (AMI); the adjusted relative risk (RR)
      of sudden death was significantly increased in depressed patients but, after
      adjustment for dyspnea/fatigue (a common symptom for heart disease and
      depression), the RR was no longer statistically significant. However, when the
      cognitive-affective depressive symptoms were examined separately from the somatic
      ones (dyspnea/fatigue, etc.), there was a clear trend for an association between
      cognitive-affective symptoms and sudden death. Because a risk factor can be
      defined as 'independent' only in a multivariate analysis in which variables are
      dichotomized, the presence of common symptoms between heart disease and
      depression represents a very difficult problem. However, taken together, the
      results of studies carried out in the general population and in patients with AMI
      strongly suggest that depression is a significant risk factor for sudden death.

PMID- 18334890
TI  - Early adenosine receptor activation ameliorates spinal cord reperfusion injury.
AB  - OBJECTIVES: Adenosine receptor activation at reperfusion has been shown to
      ameliorate ischemia-reperfusion injury of the spinal cord, but the effects of
      therapy given in response to ischemic injury are unknown. We hypothesized that
      adenosine receptor activation with ATL-146e would produce similar protection from
      ischemic spinal cord injury, whether given at reperfusion or in a delayed
      fashion. METHODS: Twenty-two New Zealand white rabbits were divided into three
      groups. All three groups, including the ischemia-reperfusion group (IR, n = 8),
      underwent 45 min of infrarenal aortic occlusion. The early treatment group
      (early, n = 8) received 0.06 mug/kg/min of ATL-146e for 3 h beginning 10 min
      prior to reperfusion. The delayed treatment group (delayed, n = 6) received ATL
      146e starting 1 h after reperfusion. After 48 h, hind limb function was graded
      using the Tarlov score. Finally, lumbar spinal cord neuronal cytoarchitecture was
      evaluated. RESULTS: Hemodynamic parameters were similar among the groups. Hind
      limb function at 48 h was significantly better in the early group (3.5 +/- 1.0)
      compared to the IR group (0.625 +/- 0.5, P < or = 0.01). There was a trend
      towards better hind limb function in the early group compared to the delayed
      group (2.4 +/- 1.1, P = 0.08). Hind limb function was similar between delayed and
      IR groups. Hematoxylin-eosin spinal cord sections demonstrated preservation of
      viable motor neurons in the early group compared to the delayed and IR groups.
      CONCLUSIONS: Early therapy with ATL-146e provided better protection in this
      study; therefore, therapy should not be delayed until there is evidence of
      ischemic neurological deficit. This study suggests that adenosine receptor
      activation is most effective as a preventive strategy at reperfusion for optimal
      protection in spinal cord ischemia-reperfusion injury.

PMID- 18334891
TI  - Congenital heart disease in live-born children: incidence, distribution, and
      yearly changes in the Campania Region.
AB  - OBJECTIVES: Congenital heart disease (CHD), the most common cardiac malformation
      in the fetal and neonatal period, represents a heterogeneous group of defects
      with little known cause. The aim of this study was to investigate the incidence
      rate (IR) of CHD without spontaneous resolution in the first year of life, the
      age at diagnosis, the most common type of CHD, and the IR changes in severe and
      nonsevere CHD during the study period. METHODS: From January 1997 to December
      2002, 4559 live births with CHD (diagnosed until December 2004) were enrolled in
      the Campania Region. Number of live-born children by month was derived from
      national registries. RESULTS: About 70% of CHD patients were diagnosed within the
      first year of life. The overall mean regional IR of CHD was 11.1 (confidence
      interval 10.8-11.4) patients per 1000 live-born children. The overall mean IR of
      CHD was significantly different in the five provinces of the Campania Region, but
      the annual IR remained stable in each of them throughout the study period. The
      relative risk in live-born children and residents in the areas with an elevated
      IR of CHD was higher for nonsevere CHD, but of low significance for severe CHD.
      At least one-third of CHD patients had atrial septal defects. CONCLUSIONS: We
      described the highest IR of CHD from one of the largest samples used up to now
      for this purpose (410 181 live-born children), but we think that this value could
      be higher (poor surveillance in some areas). Moreover, this study increases the
      awareness that CHD patients with a few symptoms are frequently underdiagnosed in
      areas with inadequate health services and that by an improved availability of
      pediatric echocardiographic assesments seem warranted. Eight years of
      surveillance and an increasing attention of both pediatricians and cardiologists
      to mild CHD in some provinces allowed us to demonstrate that, despite previous
      reports, the most common CHD in our region was atrial septal defect.

PMID- 18334893
TI  - Women and peripheral arterial disease: same disease, different issues.
AB  - OBJECTIVES: Atherosclerosis is a multifactorial disease and, thus, its clinical
      manifestations are likely to present gender-specific differences with respect to
      their development, course, symptom complexes and prognosis. The present study
      aimed to examine sex differences in peripheral arterial disease (PAD) and its
      clinical correlates. METHODS: PAD severity, quality of life (assessed by ST-22),
      cardiovascular risk factors, inflammatory profile and comorbidity were assessed
      in 163 men and 68 women who were consecutively diagnosed with PAD at three
      Italian University vascular centres. RESULTS: Compared to men, women showed a
      higher prevalence of critical limb ischemia (P = 0.018), but had a less impaired
      quality of life (assessed by ST-22), and were less likely to have a history of
      lower extremity revascularization. Furthermore, women tended to be older (P =
      0.058), and more likely to present hypercholesterolemia (P = 0.053), diabetes
      mellitus (P = 0.001), body mass index > or = 30 kg/m2 (P = 0.003) and metabolic
      syndrome (P = 0.001). Conversely, C-reactive protein plasma levels were similar
      in the two groups. No gender-specific difference was observed in cardiovascular
      comorbidity; however, the condition showing the strongest association with
      coronary artery disease was diabetes mellitus in women (odds ratio = 4.96, P =
      0.021), and smoking in men (odds ratio = 2.66, P = 0.008). CONCLUSION: In PAD,
      there are several sex differences in baseline characteristics, especially with
      respect to the weight and significance of cardiovascular risk factors. Knowledge
      of these differences may help achieve optimal gender-specific cardiovascular risk
      prevention.

PMID- 18334892
TI  - Impact of acute renal failure following percutaneous coronary intervention on
      long-term mortality.
AB  - BACKGROUND: Acute renal failure (ARF) following percutaneous coronary
      intervention (PCI) has been shown to be associated with a worse outcome. Whether
      this event should be considered as a marker of disease severity or an independent
      contributor to mortality is still unclear. METHODS: In a multicenter, prospective
      cohort study we investigated the predictive variables and the impact of
      postprocedural ARF on 2-year all-cause mortality in 2860 consecutive patients
      (50% with stable angina and 50% with non-ST-elevation acute coronary syndromes)
      undergoing PCI. Serum creatinine determinations were made immediately before and
      24 h after PCI. ARF was defined as an increase in serum creatinine of > or =0.5
      mg/dl over baseline. RESULTS: One hundred and six patients (3.7%) experienced
      ARF. At logistic regression analysis, ARF was associated with pre-existing low
      values of estimated glomerular filtration rate, reduced left ventricular ejection
      fraction, hypertension, and prior coronary bypass surgery. Mortality data at 2
      years were available for all patients: 119 patients (4.16%) had died, 3.9% of
      those without and 11.3% of those with ARF (univariate hazard ratio 3.16; 95%
      confidence interval 1.68-5.94; P = 0.0004). At Cox regression analysis, the
      significant predictors of mortality were age, ejection fraction, preprocedural
      estimated glomerular filtration rate, PCI failure, atrial fibrillation, diabetes
      mellitus, and fluoroscopy time. In this comprehensive mortality model, ARF
      maintained a borderline statistical significance (hazard ratio 1.83, 95%
      confidence interval 0.98-3.44; P = 0.06). CONCLUSIONS: ARF following PCI occurs
      almost exclusively in patients with chronic kidney disease or left ventricular
      dysfunction. These risk factors are also among the most powerful predictors of
      long-term mortality and are likely to explain most of the association between
      postprocedural ARF and long-term mortality. After correction for clinical
      determinants, however, postprocedural ARF maintains a clinically significant
      impact on mortality that must be taken into account for benefit vs. risk
      evaluation of PCI in individual patients.

PMID- 18334894
TI  - Patch size, shape and orientation affect geometrical outcomes of surgical
      anterior ventricular restoration.
AB  - OBJECTIVES: To verify whether the use of a small, oval-shaped patch limits the
      trend toward re-dilatation compared to endoventricular circular patch plasty and
      leads to different geometrical and functional results in surgical anterior
      restoration. METHODS: Thirty-seven patients with ischemic cardiomyopathy after
      anterior myocardial infarction end-systolic volume index of > or =45 ml/m2,
      ejection fraction of < or =35%, and no combined mitral procedures, underwent
      surgical anterior ventricular restoration between January 2000 and April 2003: 18
      patients (group 1) were operated on using the endoventricular circular patch
      plasty technique (mean patch area 9.6 cm2) and 19 patients (group 2) received a
      small, obliquely oriented, oval-shaped patch (mean patch area 6.2 cm2). Ten
      geometrical parameters were studied preoperatively and at least 6 and 12 months
      after surgery. Data were analyzed using repeated-measures ANOVA, chi2, paired and
      unpaired Student's t-test, and binary logistic regression. RESULTS: Group 1
      showed a worsening over time in systolic and diastolic longitudinal length, end
      diastolic volume (P < 0.001), end-diastolic volume index (P = 0.006), end
      systolic volume (P = 0.005), and end-systolic volume index (P = 0.03). Group 2
      showed an improvement in percentage of akinesia and wall motion score index (P <
      0.001) and a worsening only in end-systolic diameter (P = 0.03) and end-diastolic
      volume (P = 0.04). At 12-month follow-up, ANOVA revealed that the oval patch
      positively influenced end-diastolic volume (P = 0.03), end-systolic volume (P =
      0.03), and end-systolic volume index (P = 0.05), and group 2 had a significantly
      higher number of patients with an end-systolic volume index of <45 ml/m2 (P =
      0.01). CONCLUSION: The use of a small, narrow, obliquely oriented, oval patch may
      help to prevent adverse ventricular remodeling over time.

PMID- 18334895
TI  - Drug-eluting stents for the treatment of coronary lesions in cardiac transplant
      vasculopathy: acute and mid-term clinical and angiographic outcomes.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) is the major cause of graft
      failure and death in cardiac transplant recipients after transplantation. We
      aimed to evaluate the clinical and angiographic outcomes of patients with
      evidence of CAV who were treated percutaneously with drug-eluting stents (DES
      PCI). METHODS: Between December 2002 and September 2005, we reviewed the baseline
      procedural characteristics and the clinical outcome of consecutive cardiac
      transplanted recipients with evidence of CAV treated with DES-PCI, eligible for
      at least 9 months of follow-up. RESULTS: Fifteen consecutive patients received a
      total of 18 coronary DESs. Total treated lesions were 20; 12 (60%) involved the
      left anterior descending artery. CAV was focal in nine patients, diffuse in five
      patients, and mixed in only one patient. Mean time interval from transplantation
      to DES implantation was 126 +/- 44 months. Angiographic and procedural success
      was 100%. There were no adverse in-hospital events. During follow-up (17.9 +/-
      8.4 months), two patients died of noncardiac cause. Six patients required a new
      percutaneous intervention for a repeat revascularization rate of 40%: one patient
      underwent target lesion revascularization because of in-DES restenosis, one
      patient had target vessel revascularization because of a new coronary lesion
      proximal to the stent. Finally, four more patients underwent repeat DES-PCI in a
      coronary vessel other than the treated one. CONCLUSIONS: Although DES
      implantation seems to be associated with a high procedural success rate and a low
      restenosis rate, the repeat revascularization rate due to CAV progression remains
      in nearly half of our study patients.

PMID- 18334896
TI  - Very very late thrombosis of a sirolimus-eluting stent: does suboptimal stent
      expansion take its toll even after three years?
AB  - We report the case of a 55-year-old man who underwent coronary angiography in
      2004 for early angina following anterior ST-elevation myocardial infarction.
      Angiography disclosed a critical stenosis in the proximal left anterior
      descending artery and significant stenoses in the right coronary artery and first
      obtuse marginal branch, treated with two paclitaxel-eluting stents and a
      sirolimus-eluting stent, respectively. After completion of a six-month
      thienopyridine course and while still being on lifelong aspirin, in 2007 he was
      readmitted for lateral ST-elevation myocardial infarction: angiography revealed
      stent thrombosis beginning at the proximal edge of the sirolimus-eluting stent
      implanted in the first obtuse marginal branch. Intravascular ultrasound was
      performed after thrombectomy but before balloon dilation showing suboptimal stent
      expansion and a thrombus partially adhering to the sirolimus-eluting stent. The
      procedure was then successfully completed with the implantation of another
      sirolimus-eluting stent. This clinical vignette suggests that suboptimal drug
      eluting stent deployment may be associated with stent thrombosis well after the
      traditional time frame of subacute thrombosis.

PMID- 18334897
TI  - Coronary embolism following valve surgery.
AB  - A 55-year-old man experienced chest pain on the seventh day after valve surgery.
      Coronary angiography showed embolic occlusion of the left anterior descending
      coronary artery. The lesion was treated successfully with thrombectomy using the
      angiojet rheolytic thrombectomy system, resulting in rapid mechanical
      thrombolysis and removal via the effluent lumen of the catheter. Thrombolysis in
      Myocardial Infarction 3 flow was restored.

PMID- 18334898
TI  - Thrombectomy for thrombus removal, filters for whatever else.
AB  - Although effective in reducing the total embolic burden, many current
      thrombectomy devices might not be able to prevent the liberation of plaque
      components, which have been shown to be a potential contributor to the
      development of no-reflow during primary percutaneous coronary intervention.

PMID- 18334900
TI  - Infective endocarditis: diagnostic issues and practical clinical approach based
      on echocardiography.

PMID- 18334899
TI  - Simultaneous subacute coronary drug-eluting stent thrombosis in two different
      vessels of a patient with factor V Leiden mutation.
AB  - We review the case of a 46-year-old man who underwent elective percutaneous
      coronary intervention and stenting of the left anterior descending artery and
      right coronary artery with two sirolimus- and paclitaxel-eluting stents. Four
      days after angioplasty, he was readmitted with cardiogenic shock due to acute
      anterior and inferior myocardial infarction. Coronary angiography revealed
      subacute thrombosis of both stents, and balloon dilation was performed
      successfully thereafter. The follow-up investigations revealed that the patient
      was a carrier of factor V Leiden. We hereby discuss the importance of factor V
      Leiden as the most common cause of hypercoagulable state and its probable role in
      acute and subacute coronary stent thrombosis in drug-eluting stents.

PMID- 18334901
TI  - Transcatheter ductal stenting in critical neonatal Ebstein's anomaly.
AB  - BACKGROUND: Symptomatic neonatal Ebstein's anomaly shows a very poor outcome,
      most frequently due to duct-dependent pulmonary circulation caused by functional
      pulmonary valve atresia. In this setting, percutaneous ductal stenting using high
      flexibility coronary stents might be a highly cost-effective alternative to
      systemic-to-pulmonary shunt. METHODS: Three newborns (age 4.7 +/- 2.9 days;
      weight 3.0 +/- 0.3 kg) with critical, duct-dependent tricuspid valve Ebstein's
      anomaly and functional pulmonary atresia unresponsive to prostaglandin infusion
      and multidrug vasodilator therapy, underwent duct stabilization with high
      flexibility, open-cell stents as an alternative to surgical palliation. Their
      echocardiographic picture predicted a very high mortality rate. In two cases, the
      ductus arteriosus was recanalized using a combined pharmacological (local
      prostaglandin infusion) and mechanical (hydrophilic coronary guide-wire
      manipulation) approach. RESULTS: Stent implantation increased duct diameter from
      0.5 +/- 0.7 to 3.2 +/- 0.2 mm (P < 0.0001), resulting in a significant rise in
      oxygen saturation from 67 +/- 9 to 92 +/- 4% (P < 0.00001). After the procedure,
      the patients were quickly weaned from mechanical ventilation and discharged after
      16 +/- 7 days. Uneventful spontaneous ductal closure ensued in two patients in a
      few months, and percutaneous oxygen saturation was 87 +/- 3% at the last follow
      up session (12 +/- 10 months). CONCLUSIONS: In critical newborns with severe,
      duct-dependent Ebstein's anomaly unresponsive to medical therapy, ductal stenting
      could be a reliable, safe and cost-effective alternative to either long-term
      prostaglandin treatment or surgical palliation, in view of lower-risk corrective
      surgery at older age. This option may also be attempted successfully within a few
      days of spontaneous ductal closure using a combined pharmacological and
      mechanical approach.

PMID- 18334902
TI  - PulseCath, a new short-term ventricular assist device: our experience in off-pump
      coronary artery bypass graft surgery.
AB  - We utilized a new ventricular assist device, the PulseCath catheter, to perform
      an off-pump bypass procedure in a patient with low ejection fraction. The 21 Fr
      PulseCath catheter, driven by a standard intra-aortic balloon pump console, can
      generate a pulsatile flow of 2-3 l/min. The PulseCath coupled with an intra
      aortic balloon pump device is an important tool for left ventricular assistance.

PMID- 18334903
TI  - Dynamic thrombosis associated with bare-metal stent malapposition in a patient
      with hyperhomocysteinemia.

PMID- 18334904
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy as a cause of sudden
      infant death.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy is a rarely described
      cause of sudden death among infants. We report the case of a 4-month-old male
      infant who died suddenly in his sleep. Postmortem examination revealed the
      presence of arrhythmogenic right ventricular dysplasia/cardiomyopathy.

PMID- 18334905
TI  - Three-dimensional rotational digital angiography in catheter-based congenital
      heart disease interventions.

PMID- 18334906
TI  - A case of poststernotomy pseudoaneurysm of the left internal thoracic artery.

PMID- 18334907
TI  - New advances in the treatment of schizophrenia. Introduction.

PMID- 18334908
TI  - Safety profile of iloperidone: a pooled analysis of 6-week acute-phase pivotal
      trials.
AB  - Iloperidone, a mixed D2/5-HT2 antagonist, is currently in clinical development
      for the treatment of schizophrenia. This article assesses the short-term safety
      of iloperidone using a pooled analysis of 3 phase 2, short-term acute
      schizophrenia studies conducted between 1998 and 2002 (N = 1943). Patients
      exposed to 3 dose ranges of iloperidone, another antipsychotic, or placebo were
      compared on rates of serious adverse events (SAEs), adverse events (AEs),
      extrapyramidal symptoms, akathisia, prolactin, weight and metabolic parameters,
      QTc, and other standard safety parameters. The most common treatment-related AEs
      observed with iloperidone were dizziness, headache, dry mouth, nausea, and
      insomnia. Discontinuation due to AEs was 4.8% for iloperidone, 7.6% for
      haloperidol, 6.2% for risperidone, and 4.8% for placebo. Iloperidone groups
      showed better overall performance on the Extrapyramidal Symptom Rating Scale and
      Barnes Akathisia Scale than risperidone or haloperidol groups. Patients taking
      iloperidone experienced a mild weight increase (range, 1.5-2.1 kg) similar to
      that of risperidone (1.5 kg), whereas those on haloperidol and placebo showed
      mean weight loss (-0.1 kg and -0.3 kg, respectively). QTc interval significantly
      increased across all iloperidone groups (least squares mean change from baseline
      to end point, 2.9-9.1 msec) and for haloperidol (5.0 msec). No significant QTc
      changes occurred in the risperidone or placebo groups. Iloperidone was associated
      with no change from baseline in total cholesterol, mild elevation in serum
      glucose, and slight decrease in triglycerides. Prolactin levels decreased with
      iloperidone and increased significantly with risperidone and haloperidol. These
      short-term trials suggest that iloperidone has a reassuring safety profile in
      many of the areas that are of potential concern, including relatively low dropout
      rates because of AEs, low extrapyramidal symptoms, akathisia, and prolactin
      elevation, and a modest short-term effect on weight gain.

PMID- 18334909
TI  - Four-week, double-blind, placebo- and ziprasidone-controlled trial of iloperidone
      in patients with acute exacerbations of schizophrenia.
AB  - Iloperidone is a mixed D2/5-HT2 antagonist in development for treatment of
      schizophrenia. This trial aimed to evaluate the efficacy and safety of a fixed
      dose of iloperidone in patients with acute exacerbations of schizophrenia. This
      randomized, placebo-controlled, multicenter study comprised a 1-week titration
      period and a 3-week double-blind maintenance period. Eligible patients (n = 593)
      were randomized to iloperidone 24 mg/d, ziprasidone 160 mg/d as an active
      control, or placebo. Primary efficacy variable was change from baseline in the
      Positive and Negative Syndrome Scale Total (PANSS-T) score, using a mixed-effects
      model repeated measures analysis. Iloperidone demonstrated significant reduction
      versus placebo on the PANSS-T score (P< 0.01). Significant improvement versus
      placebo was also demonstrated with ziprasidone (P < 0.05). Compared with
      ziprasidone, iloperidone was associated with lower rates of many adverse events
      (AEs) that are particularly troublesome with antipsychotics, including sedation,
      somnolence, extrapyramidal symptoms, akathisia, agitation, and restlessness;
      iloperidone was associated with higher rates of weight gain, tachycardia,
      orthostatic hypotension, dizziness, and nasal congestion as reported as an AE.
      Most AEs were mild to moderate. A similar amount of QT prolongation was observed
      with both active treatments, although no patient had a treatment-emergent
      postbaseline corrected QT interval of 500 msec or greater. The incidence of
      clinically relevant changes in laboratory parameters was comparable between
      iloperidone and ziprasidone. Iloperidone was associated with a low incidence of
      extrapyramidal symptoms. Overall, there was improvement in akathisia with
      iloperidone treatment. Iloperidone treatment was effective, safe, and well
      tolerated in patients with acute exacerbation of schizophrenia.

PMID- 18334910
TI  - Long-term efficacy and safety of iloperidone: results from 3 clinical trials for
      the treatment of schizophrenia.
AB  - This research compared the long-term efficacy and safety of iloperidone with
      those of haloperidol in individuals with schizophrenia. Data were pooled from 3
      prospective multicenter studies, each with 6-week stabilization followed by 46
      week double-blind maintenance phases. Patients were randomized to iloperidone 4
      to 16 mg/d or haloperidol 5 to 20 mg/d. Patients included in this analysis
      completed the initial 6-week phase with at least 20% reduction in Positive and
      Negative Syndrome Scale (PANSS) total score at weeks 4 and 6, had 7-item Clinical
      Global Impressions of Change (CGI-C) scores less than 4, received 1 or more doses
      of long-term phase medication, and had 1 or more efficacy/safety assessments
      during the long-term phase. The primary efficacy variable was time to relapse,
      defined as a 25% or more increase in PANSS total score, including at least a 10
      point change; discontinuation because of lack of efficacy; aggravated psychosis
      with hospitalization; or 2-point increase in the 7-item CGI-C after week 6. Of
      1644 patients randomized and 1326 completing the 6-week phase, 473 (iloperidone,
      n = 359; haloperidol, n = 114) were included in the long-term efficacy analysis,
      and 489 (iloperidone, n = 371; haloperidol, n = 118) in the safety analysis.
      Iloperidone was equivalent to haloperidol in time to relapse. The most common
      adverse events were insomnia (18.1%), anxiety (10.8%), and schizophrenia
      aggravated (8.9%) with iloperidone, and insomnia (16.9%), akathisia (14.4%),
      tremor (12.7%), and muscle rigidity (12.7%) with haloperidol. The Extrapyramidal
      Symptoms Rating Scale scores improved with iloperidone and worsened with
      haloperidol. Metabolic changes were minimal for both groups. Mean changes in
      Fridericia's QT interval correction were 10.3 msec (iloperidone) and 9.4 msec
      (haloperidol) at end point. Iloperidone demonstrated long-term efficacy
      equivalent to haloperidol and a favorable long-term safety profile, potentially
      making this agent a suitable option as maintenance therapy for schizophrenia.

PMID- 18334911
TI  - Efficacy of iloperidone in the treatment of schizophrenia: initial phase 3
      studies.
AB  - Iloperidone is an atypical antipsychotic in development for the treatment of
      schizophrenia. This report examines efficacy results from three 6-week,
      randomized, double-blind, placebo- and active comparator-controlled studies in
      patients with schizophrenia or schizoaffective disorder. Multiple doses of
      iloperidone were studied. Active comparators (haloperidol 15 mg/d, or risperidone
      4-8 mg/d) were included to confirm trial validity. The primary protocol-defined
      efficacy variable in Study 1 was change from baseline to end point in Positive
      and Negative Syndrome Scale total scores; in Studies 2 and 3, it was change in
      the Positive and Negative Syndrome Scale-derived Brief Psychiatric Rating Scale
      scores. Results were assessed through analysis of covariance using last
      observation carried forward in the intent-to-treat population. In total, 1943
      patients were randomized. At least 1 iloperidone dosing group in each study
      demonstrated significantly better efficacy than placebo (Study 1, iloperidone 12
      mg/d [P = 0.047]; Study 2, 4-8 mg/d [P = 0.012] and 10-16 mg/d [P = 0.001]; and
      Study 3, 20-24 mg/d [P = 0.010]). Active controls were also significantly more
      effective than placebo in each trial, thus validating the trials. Additional
      analysis in patients who received active treatment for at least 2 weeks indicated
      comparable efficacy score reductions at 6 weeks for patients receiving
      iloperidone 20 to 24 mg/d versus those receiving haloperidol or risperidone. Risk
      for motor-related adverse events (eg, akathisia and extrapyramidal symptoms) was
      lower with iloperidone than with risperidone and haloperidol and was generally
      similar to placebo. These trials indicate that iloperidone is effective for the
      treatment of schizophrenia.

PMID- 18334912
TI  - Apolipoprotein E genotypes are associated with lipid-lowering responses to statin
      treatment in diabetes: a Go-DARTS study.
AB  - BACKGROUND: Apolipoprotein E (APOE) genotypes have been associated with
      variations in plasma-lipid levels and with response to statins, although the
      influence of APOE on the response to statins remains controversial, especially in
      patients with diabetes. We sought to evaluate the association of the APOE
      genotype with the low-density lipoprotein cholesterol (LDLc)-lowering response to
      statins, in a large population-based cohort of patients with diabetes. METHODS
      AND RESULTS: A total of 1383 patients, commencing statins between 1990 and 2006,
      were identified from the Genetics of Diabetes Audit and Research in Tayside
      Scotland database. Statin response was determined both by the minimum LDLc
      achieved, and by the failure of the patients to reach a clinical target LDLc (<
      or =2 mmol/l). APOE genotype and potential confounding covariates were entered
      into the linear and logistic regression models. RESULTS: We found an association
      of APOE genotypes with both baseline and treatment responses. E2 homozygotes
      achieved lower LDLc levels (mean 0.6; confidence interval: 0.1-1.1 mmol/l) than
      E4 homozygotes (mean 1.7; confidence interval: 1.4-1.9 mmol/l; P=2.96 x 10).
      Minimum LDLc was associated by a linear trend with genotype. This relationship
      remained statistically significant after adjustment for baseline LDLc, adherence,
      duration, dose, smoking, and age. None of the E2 homozygotes failed to reach the
      target LDLc, compared with 32% of the E4 homozygotes (P=5.3 x 10). CONCLUSION:
      This study demonstrates the potential clinical value of the APOE genotype as a
      robust marker for LDLc responses to statin drugs, which might contribute to the
      identification of a particularly drug-resistant subgroup of patients. This marker
      provides information over and above baseline lipid levels.

PMID- 18334913
TI  - Synergistic effect of apolipoprotein E epsilon4 and butyrylcholinesterase K
      variant on progression from mild cognitive impairment to Alzheimer's disease.
AB  - OBJECTIVE: To evaluate the synergistic effects of the apolipoprotein E (APOE)
      epsilon4 and butyrylcholinesterase K-variant (BCHE-K) alleles on progression to
      Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI).
      METHODS: This was a post-hoc exploratory analysis from a 3-4-year, randomized,
      placebo-controlled study of rivastigmine in participants with MCI (InDDEx study).
      Participants who consented to genetic testing were included in the current
      analyses. The incidence of progression to AD, cognitive decline and changes in
      MRI brain volumes were investigated in participants from the placebo arm of the
      InDDEx study. RESULTS: Of the 1018 participants in the overall study, 464 were
      successfully genotyped for both APOE and butyrylcholinesterase. Of these, 68
      (14.7%) carried > or =1 APOE epsilon4 and > or =1 BCHE-K allele. The presence of
      APOE epsilon4 was associated with a significantly higher incidence of progression
      to AD whereas the presence of BCHE-K had no independent effect on progression. A
      synergistic effect of the combined presence of APOE epsilon4 and BCHE-K on the
      time to clinical diagnosis of AD and on MRI brain volumes was seen. Progression
      to AD and hippocampal volumetric loss was greatest in participants who carried
      both APOE epsilon4 and BCHE-K alleles and lowest in BCHE-K carriers without the
      APOE epsilon4 allele. CONCLUSION: In MCI, the risk of cognitive decline,
      hippocampal volumetric loss and progression to AD seems to be the greatest in
      individuals who carry at least one copy of both the BCHE-K and APOE epsilon4
      alleles.

PMID- 18334914
TI  - Common ATP-binding cassette B1 variants are associated with increased digoxin
      serum concentration.
AB  - BACKGROUND AND OBJECTIVE: Digoxin is a known substrate of ATP-binding cassette B1
      (ABCB1/MDR1). The results of studies on the association between ABCB1
      polymorphisms and digoxin kinetics, however, remain contradictory. Almost all
      studies were small and involved only single dose kinetics. The goal of this study
      was to establish ABCB1 genotype effect on digoxin blood concentrations in a large
      cohort of chronic digoxin users in a general Dutch European population. METHODS:
      Digoxin users were identified in the Rotterdam Study, a prospective population
      based cohort study of individuals aged 55 years and above. Digoxin blood levels
      were gathered from regional hospitals and laboratories. ABCB1 single nucleotide
      polymorphisms (SNPs) 1236C-->T, 2677G-->T/A, and 3435C-->T were assessed on
      peripheral blood DNA using Taqman assays. We studied the association between the
      ABCB1 genotypes and haplotypes, and digoxin blood levels using linear regression
      models adjusting for potential confounders. RESULTS: Digoxin serum levels and DNA
      were available for 195 participants (56.4% women, mean age 79.4 years). All three
      ABCB1 variants were significantly associated with serum digoxin concentration
      (0.18-0.21 microg/l per additional T allele). The association was even stronger
      for the 1236-2677-3435 TTT haplotype allele [0.26 mug/l (95% CI 0.14-0.38)], but
      absent for other haplotypes (CGC allele considered referent), suggesting an
      interaction of SNPs in a causal haplotype instead of individual SNP effects.
      CONCLUSION: We found that the common ABCB1 1236C-->T, 2677G-->T, and 3435C-->T
      variants and the associated TTT haplotype were associated with higher digoxin
      serum concentrations in a cohort of elderly European digoxin users in the general
      population.

PMID- 18334915
TI  - Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular
      concentration in transplant recipients.
AB  - OBJECTIVE: The expression on lymphocytes of P-glycoprotein, an efflux transporter
      encoded by the ABCB1 gene, might influence cyclosporine intracellular
      concentration. METHODS: ABCB1 genotypes, cyclosporine intracellular and blood
      concentrations were determined in 64 stable renal, liver or lung transplant
      recipients. RESULTS: Cyclosporine intracellular concentration correlated
      moderately with blood concentration (r=0.30, P<0.00005). The ABCB1 1199A carriers
      presented a 1.8-fold decreased cyclosporine intracellular concentration (P=0.04),
      whereas the 3435T carriers presented a 1.7-fold increase (P=0.02) as well as a
      1.2-fold increased blood concentration (P=0.04). In contrast, ABCB1 61A>G,
      1236C>T and 2677G>T polymorphisms did not influence cyclosporine intracellular
      and blood concentrations. CONCLUSION: This is the first report demonstrating that
      ABCB1 polymorphisms influence cyclosporine intracellular concentration.
      Interestingly, its influence on intracellular concentration is significantly
      higher than on blood concentration (P<0.002). This may therefore modulate
      cyclosporine immunosuppressive activity.

PMID- 18334916
TI  - Pathway-based association analysis of genome-wide screening data suggest that
      genes associated with the gamma-aminobutyric acid receptor signaling pathway are
      involved in neuroleptic-induced, treatment-resistant tardive dyskinesia.
AB  - OBJECTIVE: Neuroleptic-induced tardive dyskinesia (TD) is an involuntary movement
      disorder that develops in patients who have undergone long-term treatment with
      antipsychotic medications, and its etiology is unclear. In this study, a genome
      wide association screening was done to identify the pathway(s) in which genetic
      variations influence susceptibility to neuroleptic-induced TD. METHODS: Screening
      with Sentrix Human-1 Genotyping BeadChip (Illumina, San Diego, California, USA)
      was done for 50 Japanese schizophrenia patients with treatment-resistant TD and
      50 Japanese schizophrenia patients without TD. A total of 40 573 single
      nucleotide polymorphisms that were not in linkage disequilibrium with each other
      and were located in the exonic and intronic regions of 13 307 genes were
      analyzed. After gene-based corrections, P values for allelic associations were
      subjected to canonical pathway-based analyses with Ingenuity Pathway Analysis
      software (Ingenuity Systems, Inc., Redwood City, California, USA). RESULTS: Eight
      genes (ABAT, ALDH9A1, GABRA3, GABRA4, GABRB2, GABRAG3, GPHN, and SLC6A11)
      contained polymorphisms with gene-based corrected allelic P values of less than
      0.05. They were aggregated significantly in 33 genes belonging to the gamma
      aminobutyric acid (GABA) receptor signaling pathway (P=0.00007, corrected
      P=0.01). Associations were replicated in an independent sample of 36 patients
      with TD and 136 patients without TD for polymorphisms in SLC6A11 (GABA
      transporter 3) (P=0.0004 in the total sample), GABRB2 (beta-2 subunit of GABA-A
      receptor) (P=0.00007 in the total sample), and GABRG3 (gamma-3 subunit of GABA-A
      receptor) (P=0.0006 in the total sample). CONCLUSION: The results suggest that
      the GABA receptor signaling pathway may be involved in genetic susceptibility to
      treatment-resistant TD, at least in a subgroup of Japanese patients with
      schizophrenia. The present results suggest that benzodiazepines may be considered
      as possible treatment option for TD.

PMID- 18334917
TI  - Sterol regulatory element binding protein 1 interacts with pregnane X receptor
      and constitutive androstane receptor and represses their target genes.
AB  - OBJECTIVE: Sterol regulatory element binding protein 1 (SREBP-1) is a lipogenic
      transcription factor of the basic helix-loop-helix family. SREBP-1 binds to
      sterol regulatory elements (SREs) in the promoter of lipogenic genes and induces
      fatty acid and triglyceride synthesis. Decreased drug clearance has been observed
      in obese and other dyslipidemic rodents as well as in diabetic, obese or overfed
      rodents. A hallmark of these conditions is increased expression of SREBP-1 in the
      liver. We therefore searched for a possible link between regulation of
      cytochromes P450 (CYPs) and SREBP-1. METHODS: We combined gene expression
      analysis, lipid analysis, effects of high levels of SREBP-1 in hepatocyte
      cultures to characterize the effects and protein interaction and chromatin
      immunoprecipitation assays to define the underlying mechanism. Finally, mice were
      fed a diet enriched in cholesterol to demonstrate the relevance of our data in
      vivo. By analyzing gene expression and lipids in cholesterol-fed mice or
      transfection of recombinant SREBP-1 in hepatocyte cultures the effect on CYPs was
      characterized. By use of protein interaction assays and chromatin
      immunoprecipitation the underlying mechanism was defined. RESULTS: We observed
      that SREBP-1 represses drug-mediated induction of hepatic CYPs, mainly members of
      the 2B and the 3A subfamilies. These drugs induce transcription of CYPs and other
      drug metabolizing enzymes via activation of the nuclear receptors pregnane X
      receptor (PXR) and constitutive androstane receptor (CAR). Here we report that
      the activation of SREBP-1 by insulin or cholesterol in mouse liver and primary
      human hepatocytes inhibits the transcriptional effects in PXR and CAR. Our
      results suggest that SREBP-1 functions as a non-DNA binding inhibitor and blocks
      the interaction of PXR and CAR with cofactors such as steroid receptor
      coactivator 1. Consequently, mRNA induction of CYPs by drugs and other
      xenochemicals is impaired. CONCLUSION: We conclude that PXR and CAR respond to
      lipid accumulation by direct interaction with SREBP-1 and show that drug
      metabolism and lipid metabolism are interconnected within a complex network of
      transcriptional regulators.

PMID- 18334918
TI  - CYP3A5 genotype is not associated with a higher risk of acute rejection in
      tacrolimus-treated renal transplant recipients.
AB  - OBJECTIVE: Patients expressing the tacrolimus-metabolizing enzyme, cytochrome
      P450 (CYP) 3A5, require more tacrolimus to reach target concentrations. We
      studied the influence of the CYP3A5(*)3 allele, which results in the absence of
      CYP3A5 protein, on tacrolimus dose and exposure, as well as the incidence of
      biopsy-proven acute rejection (BPAR) after renal transplantation. METHODS: A
      total of 136 patients participating in a prospective, randomized-controlled
      clinical trial with the primary aim of comparing the efficacy of a fixed-dose
      versus a concentration-controlled mycophenolate mofetil immunosuppressive
      regimen, were genotyped for CYP3A5(*)3. The patients described herein,
      participated in a pharmacogenetic substudy and were all treated with
      mycophenolate mofetil, corticosteroids and tacrolimus. Tacrolimus predose
      concentrations (C(0)) were measured on day 3 and 10, and month 1, 3, 6 and 12.
      RESULTS: Compared with CYP3A5(*)3/(*)3 individuals (n=110), patients carrying at
      least one CYP3A5(*)1 (wild-type) allele (CYP3A5 expressers; n=26) had a lower
      tacrolimus C(0) on day 3 only (16.6 versus 12.3 ng/ml, respectively), whereas
      dose-corrected tacrolimus C(0) were significantly lower in the latter group at
      all time points. After day 3, the overall daily tacrolimus dose was 68% higher in
      CYP3A5 expressers (P<0.001). The incidence of BPAR was comparable between CYP3A5
      expressers and nonexpressers (8 versus 16%, respectively; P=0.36). CONCLUSION: We
      conclude that patients expressing CYP3A5 need more tacrolimus to reach target
      concentrations and have a lower tacrolimus exposure shortly after
      transplantation. This delay in reaching target concentrations, however, did not
      result in an increased incidence of early BPAR and therefore, genotyping for
      CYP3A5 is unlikely to improve short-term transplantation outcome.

PMID- 18334919
TI  - High arsenic metabolic efficiency in AS3MT287Thr allele carriers.
AB  - OBJECTIVES: Epidemiological data indicate the existence of wide interindividual
      differences in arsenic metabolism. It has recently been shown that
      arsenic(III)methyltransferase (AS3MT) enzyme catalyses the methylation of
      arsenite and monomethylarsonous acid (MMA). Thus, genetic variations in the AS3MT
      gene could explain, at least partly, the interindividual variation in the
      response to arsenic exposure. In an earlier study, we have demonstrated that the
      AS3MT Met(287)Thr (C/T) polymorphism affected the urinary arsenic profile in a
      Chilean group of men (n=50) occupationally exposed to arsenic. METHODS: To
      confirm, the influence of the Met(287)Thr polymorphism in the metabolism of
      arsenic, a total of 207 Chilean men working at the copper industry were genotyped
      and their urinary profiles determined. RESULTS: The results confirm that
      Met(287)Thr polymorphism does influence arsenic metabolism in this population.
      Those carriers of the variant ((287)Thr) had a higher methylation efficiency,
      excreting 4.63% more MMA in urine (P=0.0007) and presenting a 2.98 times higher
      odd of excreting levels of MMA over the standard (P=0.011) than the participants
      homozygous for the normal allele. CONCLUSION: We can conclude that individuals
      with the (287)Thr variant display increased arsenic methylation; thus, those
      participants might be at increased risk for the toxic and genotoxic effects of
      arsenic exposure.

PMID- 18334920
TI  - Influence of genetic polymorphisms on intestinal expression and rifampicin-type
      induction of ABCC2 and on bioavailability of talinolol.
AB  - OBJECTIVES: To evaluate whether ABCC2 gene polymorphisms are associated with
      expression and/or function of the efflux pump. METHODS: We investigated the
      allele frequency of ABCC2 -24C>T, -23G>A, c.1249G>A, c.1446C>G, c.1457C>T,
      c.2302C>T, c.2366C>T, c.3542G>T, c.3561G>A, c.3563T>A, c.3972C>T, c.4348G>A, and
      4544G>A in 374 nonrelated German healthy volunteers and determined the impact on
      duodenal mRNA and protein content of ABCC2. For functional analysis, the
      disposition of intravenously (30 mg) and orally administered talinolol (100 mg)
      was measured among 31 individuals. Moreover, the effects of rifampicin-type
      induction (600 mg, 8 days) of duodenal ABCC2 were quantified in 22 participants
      with regard to genetic polymorphisms. RESULTS: The allele frequencies were 18.3%
      (-24T), 21.1% (1249A), 1.4% (1446G), 0.1% (3542T), 4.5% (3563A), 34.2% (3972T),
      and 4.4% (4544A); carriers of -23G>A, 1457C>T, 2302C>T, 2366C>T, 3561G>A, and
      4348G>A were not identified. The -24T allele was in strong linkage with 3972T,
      and 3563A with 4544A, whereas 1249A was weakly linked with other variant alleles.
      None of the single nucleotide polymorphisms investigated influenced significantly
      intestinal ABCC2 mRNA and protein content. The variant ABCC2 1249G>A (V417I),
      however, was associated with lower oral bioavailability (P=0.001), and increased
      residual clearance of intravenous talinolol (P=0.021). Intestinal ABCC2 mRNA and
      protein expression were upregulated by rifampicin treatment, a genetic influence
      could be detected in only four cases heterozygote for 3563T>A or 4544G>A.
      CONCLUSION: The 1249G>A (V417I) polymorphism is obviously associated with higher
      activity of the intestinal transporter.

PMID- 18334921
TI  - Changes in consensus arylamine N-acetyltransferase gene nomenclature.
AB  - Changes in consensus arylamine N-acetyltransferase (NAT) gene nomenclature
      determined at the 2007 International NAT Workshop include: (1) Alleles in all
      species except mouse and rat are all uppercase. For mouse and rat, the first
      letter is upper case followed by lower case. (2) The nomenclature system is now
      species-specific. Thus, NAT2(*)1 (chicken), NAT2(*)2 and NAT2(*)3 (rabbit),
      Nat2(*)8 Nat2(*)9, Nat2(*)22 and Nat2(*)23 (mouse), NAT2(*)15, NAT2(*)16A and
      NAT2(*)16B (Syrian hamster), and NAT2(*)20, NAT2(*)21A and NAT2(*)21B (rat) are
      retired and renumbered within a species. A species modifier incorporated into the
      allele designation is written in upper case Roman font, e.g., (MOUSE)Nat1(*)1 is
      now the reference Nat1 allele in mouse; and (3) The NAT website also can now be
      accessed at a webalias address: http://N
      acetyltransferasenomenclature.louisville.edu. New NAT alleles should continue to
      be submitted to the NAT Nomenclature Committee for inclusion on the website to
      ensure proper categorization and to continue consistency in nomenclature.

PMID- 18334922
TI  - The Arg16Gly variant of the beta2-adrenergic receptor predisposes to hypoglycemia
      unawareness in type 1 diabetes mellitus.
AB  - Hypoglycemia unawareness has been linked to desensitization of the beta2
      adrenergic receptor. Desensitization of the beta2-adrenergic receptor (ADRB2) is
      genetically determined by the Arg16Gly variant of this receptor. We tested the
      hypothesis that hypoglycemia unawareness is more common among patients homozygous
      for the Gly16 variant. We performed genotyping of the A265G (Arg16Gly)
      polymorphism in the ADRB2 gene in 85 patients with type 1 diabetes and classified
      them according to hypoglycemia awareness status. A total of 45 patients (53%)
      were homozygous for Gly16, 32 patients (38%) were heterozygous and eight patients
      (9%) were homozygous for Arg16. Hypoglycemia unawareness was 3.4-fold more common
      among patients homozygous for Gly16 than among patients with other variants of
      the Arg16Gly polymorphism (P=0.014). We conclude that patients with type 1
      diabetes who carry two alleles of the Gly16 variant of ADRB2 are at increased
      risk of developing hypoglycemia unawareness. Future studies are required to
      confirm these results in larger, independent populations.

PMID- 18334923
TI  - The incidence of peripheral nerve injury in extremity trauma.
AB  - OBJECTIVE: To examine the incidence of peripheral nerve injury within 90 days of
      a limb trauma diagnosis in patients who have presented to the hospital or
      outpatient clinic. DESIGN: This study is a retrospective, descriptive study that
      uses the 1998 MarketScan Commercial Claims and Encounters Database (The MEDSTAT
      Group) to track peripheral nerve injuries in extremity trauma. We selected our
      sample by using ICD9 codes for limb trauma during the first 9 mos of 1998. Nerve
      injuries within 90 days after limb trauma were the main outcome measure. Finally,
      we report how the rates of trauma and accompanying nerve injuries were contrasted
      by gender and age group, using univariate and bivariate statistics. All data
      analyses were conducted using Stata 9.0 statistical software. RESULTS: Out of 16
      million insureds in the database, 220,593 (1.4%) were diagnosed with limb trauma.
      Eighty-three percent of the patients were less than 55 yrs old, and 50% were
      male. The total incidence of nerve injuries within 90 days of upper- or lower
      limb trauma was 1.64%. The type of extremity trauma with the highest incidence of
      nerve injury within 90 days of the diagnosis was a crush injury at 1.9%.
      Approximately 50% of our sample was selected because of a dislocation, which had
      an associated nerve injury prevalence of 1.46%. CONCLUSIONS: When looking at the
      population sampled, rates for peripheral nerve injury in people incurring limb
      trauma are low. Crush injuries seem to have the highest rate of associated nerve
      injury. Further studies are needed to observe outcomes for people with nerve
      damage after trauma.

PMID- 18334924
TI  - [Emerging therapy in rheumatoid arthritis].
AB  - Rheumatoid arthritis (RA) is a chronic disease leading to disability. The
      inflammatory process resulting from autoimmunization involves mainly small joints
      of the hands and feet, but also can involve all joints and internal organs.
      Progress in immunology has caused an increase in understanding the RA
      pathogenesis, resulting in new methods of treatment. The breakthrough in RA
      therapy was initiated by TNF- alpha inhibitors, introduced during the last 10
      years. TNF- alpha inhibitors were the first medications allowing improvement of
      disease outcome. However, more than half of patients do not achieve ACR50
      improvement criteria, remission is rare, and the treatment is associated with
      side effects. Therefore, new and better drugs are being sought. In this review,
      new preparations for RA treatment currently under preclinical and clinical
      examination are described.

PMID- 18334925
TI  - Serum and peritoneal evaluation of vitamin D-binding protein in women with
      endometriosis.
AB  - INTRODUCTION: Vitamin D-binding protein (also called DBP or Gc-globulin) is
      recognized as a multifunctional protein involved in the action scavenger system,
      the transport of vitamin D sterols, and the modulation of immune and inflammatory
      responses. This study evaluated total serum and peritoneal concentrations of
      vitamin D-binding protein in women with endometriosis, known as an inflammation
      associated disease. MATERIALS/METHODS: The total concentration of DBP was
      measured with an enzyme-linked immunosorbent assay (ELISA) using a polyclonal
      antibody raised in a goat immunized with human DBP. Serum and peritoneal fluid
      were collected from women with endometriosis (n=26) and from patients with benign
      gynecological conditions serving as a control group (n=17). RESULTS: In general,
      the vitamin D-binding protein concentration was higher in serum than in
      peritoneal fluid. Women with endometriosis had higher serum but lower peritoneal
      levels of DBP compared with the control group; however, no significance was
      noted. When the endometriosis group was divided with regard to severity, an
      insignificantly higher serum level of DBP was observed in advanced endometriosis
      compared with the mild form of the disease, whereas the peritoneal concentration
      was not dependent on disease severity. CONCLUSIONS: It is concluded that serum
      and peritoneal DBP concentrations are not affected in women with endometriosis;
      however, based on the latest published data, it is possible that both the serum
      and peritoneal concentrations of vitamin D-binding protein may be dependent on Gc
      genotype, which results in differential modulation of monocyte/macrophage
      activity.

PMID- 18334926
TI  - [The Rho protein family and its role in the cellular cytoskeleton].
AB  - Proteins of the Rho protein family (RhoA, Rac1, Cdc42) work as molecular switches
      in the regulation of many cellular processes. They are involved in cell
      migration, cell-cycle control, apoptosis, and the regulation of gene
      transcription. Rho proteins show their activity mainly in the cell's cytoskeleton
      by taking part in the reorganization of microfilaments and microtubules. In
      recent years, significant progress has been made in understanding the biochemical
      and genetic nature of many processes controlled by Rho proteins. Although there
      are still seveal unknowns and hypothesizes which require confirmation, newer and
      more precise experimental results allow us to better understand these processes.
      It has also been suggested to use Rho family proteins in the therapy of some
      diseases. The purpose of this study was to characterize the significance of Rho
      processes in the cellular cytoskeleton.

PMID- 18334927
TI  - Hypoxia-regulated components of the U4/U6.U5 tri-small nuclear riboprotein
      complex: possible role in autosomal dominant retinitis pigmentosa.
AB  - PURPOSE: High oxygen consumption and cyclical changes related to dark-adaptation
      are characteristic of the outer retina. Oxygenation changes may contribute to the
      selective vulnerability of the retina in retinitis pigmentosa (RP) patients,
      especially for those forms involving genes with global cellular functions. Genes
      coding for components of the U4/U6.U5 tri small nuclear ribonucleoprotein (tri
      snRNP) complex of the spliceosome stand out, because mutations in four genes
      cause RP, i.e., RP9 (PAP1), RP11 (PRPF31), RP13 (PRPF8), and RP18 (PRPF3), while
      there is no degeneration outside the retina despite global expression of these
      genes. With the assumption that variable oxygenation plays a role in RP forms
      related to pre-mRNA splicing and the retina and brain are similar, we searched a
      data collection of ischemia-hypoxia regulated genes of the brain for oxygen
      regulated genes of the U4/U6.U5 tri-snRNP complex. METHODS: A database of
      ischemia-hypoxia response (IHR) genes in the brain was generated from gene
      expression profiling studies [n=24]. Public databases (NCBI) were searched for RP
      genes with global function that are expressed in the brain. From the IHR gene
      list, we extracted genes that were directly related to retinal degeneration
      through a listed mutation (OMIM, Retnet, RISN). The database was then examined
      for indirect links to RP forms affecting the U4/U6.U5 tri-snRNP complex by
      searching for IHR genes contributing to this complex. Potential expression of
      matched genes in the retina was ascertained using NEIBank. Immunohistochemistry
      was used to localize a selected protein of the U4/U6.U5 tri-snRNP complex in
      cynomolgus monkey and human retina specimens. RESULTS: The approach identified
      genes that cause retinal degeneration (CNGB1, SEMA4A, RRG4) or developmental
      changes (SOX2) when mutated. One IHR gene, Pim1, is the immediate binding partner
      for PAP1 (RP9). Three IHR genes linked the U4/U6.U5 tri-snRNP complex to
      regulation by oxygenation: PRPF4; SART1, also known as 110 kDa SR-related protein
      of the U4/U6.U5 tri-snRNP or as hypoxia associated factor (HAF); and LSM8, U6
      snRNA-associated Sm-like protein. The 110 kDa SR-related protein was localized in
      all retinal cells including photoreceptors. CONCLUSIONS: Regulation by changes in
      oxygenation within the U4/U6.U5 tri-snRP complex could be particularly important
      for photoreceptors where oxygen consumption follows a circadian rhythm. If the
      U4/U6.U5 tri-snRP complex is already impaired by mutations in any of the four
      genes causing RP, it may be unable to follow properly the physiological demands
      of oxygenation which are mediated by the four hypoxia-regulated proteins emerging
      in this study. Selective vulnerability may involve complex combinations of widely
      expressed genes, specific cellular functions and local energy availability.

PMID- 18334928
TI  - Analysis of LOXL1 polymorphisms in a United States population with
      pseudoexfoliation glaucoma.
AB  - PURPOSE: To identify if recently described LOXL1 (lysyl oxidase-like 1)
      polymorphisms are associated with pseudoexfoliation glaucoma (XFG) in a United
      States (U.S.) Caucasian patient population. METHODS: Individuals with XFG were
      identified using standard clinical examination techniques. TaqMan allelic
      discrimination assays were used to genotype 13 single nucleotide polymorphisms
      (SNPs) that tag LOXL1 in Caucasian individuals. The coding region of exon 1 that
      includes the previously associated SNP, rs1048661, was sequenced. Allele and
      genotype frequencies were compared between cases and unrelated controls. RESULTS:
      Fifty affected individuals and 235 control individuals were recruited into this
      study. We replicated the previously reported association of three SNPs
      (rs1048661, rs2165241, and rs3825942) in our independent XFG population (single
      SNP p-values were 0.001-0.02). The risk alleles at these three and several other
      intragenic SNPs are part of an extended XFG-associated LOXL1 haplotype with a
      frequency of 32.0% in XFG patients and 21.6% in controls. CONCLUSIONS: We have
      performed an analysis of LOXL1 and XFG in a United States patient population and
      have confirmed the strong association previously reported for Icelandic and
      Swedish samples. However, due to the high frequency of risk alleles in non-XFG
      individuals, this association should not form the basis of a diagnostic test for
      XFG. It is likely that additional genetic or environmental factors modulate the
      penetrance of LOXL1 susceptibility alleles.

PMID- 18334929
TI  - Effect of circulation on the disposition and ocular tissue distribution of 20 nm
      nanoparticles after periocular administration.
AB  - PURPOSE: Our previous studies indicated that while 20 nm particles are rapidly
      cleared from the periocular space of the rat following posterior subconjunctival
      injection, 200 nm particles persisted for at least two months. To understand
      faster clearance of 20 nm particles, the purpose of this study was to determine
      transscleral permeability and in vivo disposition in the presence and absence of
      circulation. Further, it was the purpose of this study to simulate sustained
      retinal drug delivery after periocular administration of rapidly cleared and
      slowly cleared nanoparticles. METHODS: The permeability of 20 and 200 nm
      particles over 24 h was examined across isolated bovine sclera and sclera-choroid
      RPE with or without a surfactant (Tween 20, 0.1% w/v) added to the preparation.
      The in vivo disposition of nanoparticles was performed using Sprague Dawley rats.
      The rats, either dead or alive, were administered with 400 microg of the
      nanoparticles in the periocular space, and the particle disposition in the eye
      tissues was assessed 6 h later. To evaluate the role of the reticulo-endothelial
      system and lymphatic circulation, isolated liver, spleen, and cervical, axillary,
      and mesenteric lymph nodes were analyzed using confocal microscopy. Mathematical
      simulations with Berkeley Madonna were used to evaluate the effect of
      nanoparticle size on retinal drug levels following periocular administration.
      Celecoxib was used as the model drug and the finalized pharmacokinetic model from
      a previous study was used with some modifications for the simulation. RESULTS:
      Transport of 20 nm particles across sclera in the presence and absence of the
      surfactant were 0.1%+/-0.07% and 0.46%+/-0.06%, respectively. These particles did
      not permeate across the sclera-choroid-RPE in 24 h. There was no quantifiable
      transport for 200 nm particles across the sclera or the sclera-choroid-RPE. In
      live animals, the 20 nm particles were undetectable in any of the ocular tissues
      except in the sclera-choroid following periocular administration; however, in
      dead animals, the particle concentrations in the sclera-choroid were 19 fold
      higher than those in live animals, and particles were detectable in the retina as
      well as vitreous. The retention of 20 nm particles at the site of administration
      was two fold higher in the dead animals. In live animals, the particles were
      clearly detectable in the spleen and to a very low extent in the liver as well.
      The particles were also detected in the cervical, axillary, and mesenteric lymph
      nodes of the live animals. Simulations with two particles (20 nm and 200 nm) with
      different clearance rates demonstrated that the retinal drug levels were affected
      by particle clearance. Larger nanoparticles sustained retinal drug delivery
      better than smaller nanoparticles. With an increase in drug release rate from the
      particles, these differences diminish. CONCLUSIONS: The 20 nm particles are
      transported across the sclera to a minor degree; however, there is no significant
      transport across the sclera-choroid-RPE. Periocular circulation (blood and
      lymphatic) plays an important role in the clearance of the 20 nm particles. The
      higher particle levels in the ocular tissues in the post-mortem studies indicate
      a dynamic physiologic barrier to the entry of particles into the ocular tissues
      after periocular administration. The particle size of the delivery system can
      play an important role in the observed retinal drug levels after periocular
      administration. Slow release nanoparticles with low clearance by blood and
      lymphatic circulations are suitable for prolonged transscleral drug delivery to
      the back of the eye.

PMID- 18334930
TI  - A novel de novo PAX6 mutation in an Ashkenazi-Jewish family with aniridia.
AB  - PURPOSE: To report a novel de novo PAX6 mutation in an Ashkenazi-Jewish family
      with autosomal dominant aniridia. METHODS: A mother and her daughter of Ashkenazi
      Jewish origin were diagnosed with aniridia. Blood samples were drawn from family
      members and DNA was analyzed by direct sequencing and microsatellite marker
      analysis. RESULTS: The index patient and her daughter were affected with aniridia
      accompanied by congenital cataract, nystagmus, and glaucoma. A heterozygous PAX6
      frameshift mutation in exon 6 (c.577_578insG, insG@Gly72) was identified in the
      affected individuals and not in any of the unaffected family members including
      the parents of the index patient. Microsatellite analysis revealed that the index
      patient inherited the disease haplotype from her unaffected father. A sequence
      analysis of human PAX6 expressed sequence tags revealed the identification of
      spliced transcripts initiating from introns 4, 6, 7, 8, and 11. CONCLUSIONS: A
      novel de novo frameshift mutation in PAX6, which presumably occurred in the
      paternal gamete, was found in a family with autosomal dominant aniridia. The
      location of the mutation suggests that only full-length PAX6 isoforms would be
      disrupted, indicating that the normal expression of shorter, paired-less, protein
      isoforms cannot prevent manifestation of the disease.

PMID- 18334931
TI  - Tear lipocalin is the major endonuclease in tears.
AB  - PURPOSE: Human endonucleases are integral to apoptosis in which unwanted or
      potentially harmful cells are eliminated. The rapid turnover of ocular surface
      epithelium and microbial colonization of the eyelids are continual sources of DNA
      in tears. Here, we determine the principal sources of endonuclease activity in
      tears. METHODS: Endonucleases in human tears were identified after Sephadex G100
      gel filtration. DNA hydrolyzing activity was measured by the conversion pUC19
      plasmid DNA to its circular form in agarose gels. Fractions with endonuclease
      activity were further isolated using a combination ConA-Sepharose DNA, oligo (dT)
      cellulose, and anion exchange chromatographies. The molecular weights of the DNA
      hydrolyzing proteins were estimated in zymograms and by calibration of size
      exclusion chromatography. DNase activities were characterized for activity at a
      variety of pH and ion concentrations as well as in the presence of inhibitors
      including NiCl(2), ZnCl(2), G-actin, and aurintricarboxylic acid (ATA). To
      determine the mode of hydrolysis, the cleaved ends of the DNA digested by tear
      DNases were analyzed by 3' and 5' end labeling using either terminal
      deoxynucleotidyl transferase or polynucleotide kinase with or without
      pretreatment with alkaline phosphatase. RESULTS: Tear lipocalin (TL) accounts for
      over 75% of the DNA catalytic activity in tears while a second endonuclease,
      approximately 34 kDa, is responsible for less than 24% of the activity. Both are
      Mg(2+) dependent enzyme endonucleases that are enhanced by Ca(2+), active at
      physiologic pH, inhibited by aurintricarboxylic acid, and catalyze hydrolysis of
      DNA to produce 3'-OH/5'P ends. However, the two enzymes can be distinguished by
      the inhibitory effect of NiCl(2) and the sizes of the cleaved DNA fragments.
      CONCLUSIONS: Two magnesium dependent extracellular endonucleases were identified
      in tears that are different from other major human extracellular nucleases. TL is
      the principal endonuclease in human tear fluid. Tear endonucleases have unique
      characteristics that differ from other known human endonucleases.

PMID- 18334932
TI  - Isolation and distribution of rabbit keratocyte precursors.
AB  - PURPOSE: To isolate multipotent precursors from the rabbit corneal stroma and to
      compare the distribution and proliferative capacity of keratocyte precursors
      obtained from the central and peripheral regions of the corneal stroma. METHODS:
      The rabbit corneal stroma was divided into a peripheral region (6.0-10.0 mm in
      diameter) and a central region (6.0 mm in diameter). A sphere-forming assay was
      then performed to isolate precursors from the stroma of each region. To promote
      differentiation, isolated sphere colonies were plated in wells with a medium
      containing fetal bovine serum. Expression of various markers by the sphere
      colonies and their progeny was examined using immunocytochemistry and/or reverse
      transcription polymerase chain reaction (RT-PCR). RESULTS: The rate of primary
      sphere formation by cells from the peripheral stroma (51.4+/-10.1/10,000 cells)
      was significantly higher than by cells from the central stroma (35.9+/-3.0/10,000
      cells; p=0.00021). Secondary sphere formation rate was significantly higher in
      the peripheral stroma (45.6+/-6.4/10,000 cells) than in the central stroma
      (33.4+/-2.1/10,000 cells; p=0.00002). Cells from the spheres were positive for
      CD34 and nestin. Their progeny showed a keratocyte-like spindle shape and
      expressed vimentin, alpha-smooth muscle actin, and two neural differentiation
      markers (microtubule-associated protein-2 and neuron-specific enolase).
      Expression of nestin and vimentin was confirmed by RT-PCR. CONCLUSIONS: Our
      findings demonstrate that both the peripheral and central regions of the corneal
      stroma contain a significant number of precursors, but the peripheral stroma has
      more precursors with a stronger proliferative capacity than that of cells from
      the central stroma.

PMID- 18334934
TI  - Culture and characterization of oral mucosal epithelial cells on human amniotic
      membrane for ocular surface reconstruction.
AB  - PURPOSE: To culture oral mucosal epithelial cells on deepithelialized human
      amniotic membrane without the use of feeder cells and to compare the
      characteristics of cultured oral cells with cultured limbal and conjunctival
      epithelial cells for use in ocular surface reconstruction. METHODS: Oral biopsies
      were obtained from healthy volunteers after informed consent and were cultured on
      deepithelialized amniotic membrane for three to four weeks. Confluent cultures of
      limbal, oral, and conjunctival cells were subjected to characterization of
      markers of stem cells and of epithelial differentiation by reverse-transcription
      polymerase chain reaction (RT-PCR) and by immunohistochemistry. Ultrastructural
      studies were also performed using electron microscopy. RESULTS: A sheet of
      healthy, stratified oral epithelial cells was obtained within three to four weeks
      of culture. Electron microscopy demonstrated that the cells formed gap junctions
      and desmosomes. RT-PCR analysis showed that cultured oral epithelial cells
      expressed markers of epithelial differentiation such as cytokeratin K3, K4, K13,
      K15 and connexin 43. The cells also expressed stem cell markers of epithelial
      cells such as DeltaN isoforms of p63 as well as p75, a marker for stem cells of
      oral epithelium. The cells did not express cytokeratin K12 or Pax-6, an eye
      specific transcription factor. CONCLUSIONS: Oral epithelial cells can be cultured
      as explants on deepithelialized amniotic membrane without using feeder cells.
      Characterization showed that these cells maintain the phenotypic characteristics
      of oral epithelial cells and that the culture is a heterogeneous population of
      differentiated cells and stem cells. We find the cultured oral epithelial cells
      usable for ocular surface reconstruction in patients having bilateral ocular
      surface diseases.

PMID- 18334933
TI  - Expression of senescence-related genes in human corneal endothelial cells.
AB  - PURPOSE: To investigate the expression of p16(INK4a), p21(WAF1/CIP1), p27(KIP1),
      and p53 in human corneal endothelial cell (HCEC) senescence ex vivo at various
      donor ages. METHODS: Residual corneal tissues obtained after penetrating
      keratoplasty were used in this study. Age, death-to-preservation interval, and
      preservation-to-surgery interval of the donors were recorded. Corneal endothelial
      cell survival and density were evaluated by trypan blue and alizarin red staining
      immediately after keratoplasty. Fresh frozen sections of donor corneas at various
      ages (18, 33, 54, and 68 years) were immunostained in situ. Total RNA extracted
      from age groups of 20, 30, 40, 50, and 60 years was evaluated by reverse
      transcriptase polymerase chain reaction (PCR) to reveal the expression of the
      senescence-related genes, p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53, in
      HCECs. Total RNA extracted from 20-, 24-, 26-, 30-, 50-, 55-, 56-, and 60-year
      old donor groups was subjected to real-time PCR analysis for measurement of gene
      expression. The results of the young (< or =30 years) and the old (> or = 50
      years) were compared by the unpaired t-test. Ex vivo senescence of HCECs from the
      donors at various ages (9, 17, 23, 57, 65, and 67 years) was observed by
      senescence-associated beta-galactosidase activity (SA-beta-Gal) staining at pH
      6.0. RESULTS: The mean endothelial cell density of the donor corneas was
      2,391.4+/-84.6 cells/mm(2), and the survival rate of the endothelial cells was
      84.4%+/-5.3%. Hematoxylin and eosin staining showed normal structures of the
      corneal epithelium, stroma, and endothelium. The expression and nuclear
      localization of p16(INK4a), p21(WAF1/CIP1), p27(KIP1), and p53 in HCECs were
      confirmed by immunohistochemistry in situ. Reverse transcriptase PCR examination
      showed positive target bands of each gene at each age group. An age-related
      increase in p16(INK4a) expression was observed by real-time PCR (p=0.014). There
      was no significant difference in the expression levels of p21(WAF1/CIP1),
      p27(KIP1), and p53 between the young and old donors (p=0.875, 0.472, and 0.430,
      respectively). Strong SA-beta-Gal activity was observed in the endothelial cells
      of the old donors while there was weak and little-to-no blue staining in the
      endothelia from the young. CONCLUSIONS: The population of HCECs exhibiting
      senescence-like characteristics increases with age. p16(INK4a), p21(WAF1/CIP1),
      p27(KIP1), and p53 are expressed in HCECs despite donor ages. The p16(INK4a)
      signal pathway might play a key role in the process of senescence in HCECs.

PMID- 18334935
TI  - Distribution of bovine and rabbit lens alpha-crystallin products by MALDI imaging
      mass spectrometry.
AB  - PURPOSE: To develop a general tissue preparation protocol for MALDI (Matrix
      Assisted Laser Desorption Ionization) imaging mass spectrometry of ocular lens
      tissue, and to compare the spatial distributions of alpha-crystallin and its
      modified forms in bovine and rabbit lenses. METHODS: Frozen bovine and rabbit
      lenses were cryosectioned equatorially at -20 degrees C into 12 microm-thick
      tissue sections. Lens sections were mounted onto conductive glass slides by
      ethanol soft-landing to maintain tissue integrity. An ethanol/xylene washing
      procedure was applied to each section before matrix application to facilitate
      uniform matrix crystal formation across the entire tissue section. Molecular
      images of both alpha-crystallin subunits and their modified forms were obtained
      from mass spectral data acquired at 100 microm steps across both whole rabbit and
      half bovine lens sections. RESULTS: Distinct spatial patterns for the two
      subunits of alpha-crystallin and their modified forms were observed in the rabbit
      and bovine lens sections. While alphaA-crystallin was extensively degraded in the
      lens core of both species, rabbit lenses exhibited a greater degree of larger
      molecular weight truncation products. In contrast, alphaB-crystallin degradation
      was limited in both species. Interestingly, phosphorylation of alphaA- and alphaB
      crystallin was most abundant in the middle cortex of both species. CONCLUSIONS:
      An improved method for investigating the spatial distribution of alpha-crystallin
      in the ocular lens by MALDI imaging mass spectrometry has been developed. The
      localization of multiple degradation products and specific regions of alpha
      crystallin phosphorylation in bovine and rabbit lenses gives new insight into the
      program of lens fiber cell differentiation and normal lens function.

PMID- 18334936
TI  - Localization of TGF-beta type II receptor and ED-A fibronectin in normal
      conjunctiva and failed filtering blebs.
AB  - PURPOSE: The cytokine transforming growth factor-beta (TGF-beta), and the ED-A
      splice variant of the extracellular matrix protein fibronectin modulate wound
      healing and scar formation. To further elucidate their possible role in filtering
      bleb scarring after glaucoma surgery in human eyes in vivo, we studied the cell
      type specific localization of TGF-beta receptors and the presence of ED-A
      fibronectin in sections of normal conjunctiva and scarred filtering blebs.
      METHODS: Cryosections of normal conjunctiva (four patients) and scarred filtering
      blebs (seven patients) were studied by double-label immunofluorescence.
      Antibodies against PECAM-1 and prolyl-4-hydroxylase allowed for specification of
      vascular endothelial cells and activated fibroblasts, respectively. TGF-beta
      receptor type II (TGF-beta-RII), alpha-smooth muscle actin, O-linked
      sialoglycoprotein, fibronectin and the ED-A fibronectin splice-variant were also
      detected using specific antibodies. Labeled sections were viewed with a confocal
      laser scanning microscope. RESULTS: Vascular endothelial cells expressed TGF-beta
      RII in both normal and scarred tissue. TGF-beta-RII was sparsely detected in the
      fibroblasts of normal conjunctiva while it was strongly expressed in most
      fibroblasts of the scarred filtering blebs. Similarly, ED-A fibronectin was not
      detected in the extracellular matrix of normal conjunctiva but abundantly present
      in scarred filtering blebs. CONCLUSIONS: Filtering bleb scarring is associated
      with an abundant expression of TGF-beta receptors in activated fibroblasts and
      the deposition of the fibrogenic ED-A fibronectin splice-variant. These data
      support the concept of targeting TGF-beta signaling to prevent scar formation
      after filtering glaucoma surgery.

PMID- 18334937
TI  - Epigallocatechin gallate protects against oxidative stress-induced mitochondria
      dependent apoptosis in human lens epithelial cells.
AB  - PURPOSE: Oxidative stress has long been recognized as an important mediator of
      apoptosis in lens epithelial cells and also plays an important role in the
      pathogenesis of cataracts. (-)-Epigallocatechin gallate (EGCG), the most abundant
      component in green tea, has potent antioxidant activity. The goals of this study
      were to determine the protective effect of EGCG against H(2)O(2)-induced
      apoptotic death and the possible mechanisms involved in human lens epithelial
      (HLE) cells. METHODS: HLEB-3, a human lens epithelial cell line, was exposed to
      various concentrations of H(2)O(2) and EGCG and subsequently monitored for cell
      death by the MTT assay and flow cytometric analysis using Annexin V and PI. The
      effect of EGCG in protecting HLE cells from cell death was determined by various
      assays after the cells were exposed to H(2)O(2). The ability of EGCG to block the
      accumulation of intracellular reactive oxygen species and the loss of
      mitochondrial membrane potential (Deltapsim) induced by H(2)O(2) was examined
      with dichlorofluorescein (DCF) fluorescence and 5,5',6,6'-tetrachloro-1,1',3,3'
      tetrathylbenzimidazol carbocyanine iodide (JC-1). The expression of cytochrome c,
      caspase-9, caspase-3, and Bcl-2 family proteins was measured by western blotting.
      The changed expression of the mitogen activated protein kinase (MAPK) and Akt
      pathways was also detected by western blot. RESULTS: In the present study, EGCG
      protected against cell death caused by H(2)O(2) in HLEB-3 cells. EGCG reduced the
      H(2)O(2)-induced generation of reactive oxygen species (ROS), the loss of
      mitochondrial membrane potential (Deltapsim), and the release of cytochrome c
      from the mitochondria into the cytosol. EGCG inhibited the H(2)O(2)-stimulated
      increase of caspase-9 and caspase-3 expression and the decrease of the Bcl-2/Bax
      ratio. Moreover, EGCG attenuated the reduced activation and expression of ERK,
      p38 MAPK, and Akt induced by H(2)O(2). CONCLUSIONS: These findings suggest that
      EGCG protects HLE cells from the mitochondria-mediated apoptosis induced by
      H(2)O(2) through the modulation of caspases, the Bcl-2 family, and the MAPK and
      Akt pathways.

PMID- 18334938
TI  - Oxygen and blood flow: players in the pathogenesis of glaucoma.
AB  - The increase of IOP in POAG is due an increased resistance of aqueous outflow
      through the trabecular meshwork (TM). The exact mechanisms leading to the
      corresponding changes in the TM are not yet known. We know, however, that all
      risk factors for arteriosclerosis are also risk factors for an increase in IOP.
      RESULTS: The association between IOP increase and these factors is relatively
      weak but nevertheless significant. Similar to the pathogenesis of
      arteriosclerosis, oxidative stress plays a role in the development of TM damage.
      Even less is known about the pathogenesis of glaucomatous optic neuropathy (GON).
      Obviously the risk factors for arteriosclerosis play a role via increasing the
      IOP. When corrected for IOP, however, these factors only play a minor role. In
      contrast, factors associated with disturbed autoregulation, in particular a
      systemic primary vascular dysregulation (PVD), increase the risk for GON. This is
      best observed in normal tension glaucoma patients. An insufficient autoregulation
      increases the chance for an unstable ocular perfusion and thereby an unstable
      oxygen supply. This, in turn, leads to oxidative stress. The concentration of
      superoxide (O(2)(-)) within the axons of the optic nerve head increases. If
      neighboring astrocytes are activated, either by mechanical or by ischemic stress,
      in excess produced nitric oxide (NO) molecules diffuse also into the axons and
      fuse with oxygen. The resulting peroxynitrat (ONOO(-)) diffuses within the axons
      towards the retina and the lateral geniculate nucleus and induces apoptosis.

PMID- 18334939
TI  - Cyclic GMP in the pig vitreous and retina after experimental retinal detachment.
AB  - PURPOSE: Earlier studies have revealed a decreased level of cGMP in vitreous
      fluid obtained from patients with a retinal detachment. To further investigate
      this phenomenon, we developed an experimental retinal detachment model in pigs.
      METHODS: Experimental unilateral retinal detachments were induced in pig eyes by
      subretinal injection of 0.25% sodium hyaluronate. Fourteen days later the
      vitreous and retinas were analyzed for cGMP expression. Following enucleation,
      the retinas were incubated in the presence of a nonselective phosphodiesterase
      inhibitor (IBMX), and the particulate guanylyl cyclase stimulator atrial
      natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium
      nitroprusside (SNP). cGMP was visualized in retinal wholemounts by
      immunochemistry combined with a computer based stereology system. cGMP levels in
      vitreous were determined by ELISA. RESULTS: The mean vitreous cGMP level in pig
      eyes with a retinal detachment (1.45 pmol/ml) was significantly lower compared to
      the mean level of cGMP in healthy pig eyes (4.61 pmol/ml; p=0.028 was considered
      significant). In the inner retina, ANP as well as SNP induced cGMP
      immunoreactivity in both detached and healthy retinas. After incubation with ANP,
      cGMP could also be detected in the outer nuclear layer of the detached retina,
      whereas this was not the case in the normal retina. CONCLUSIONS: Experimental
      retinal detachment in the pig eye leads to a decrease of cGMP levels in vitreous
      similar to that observed in clinical studies. This model may be helpful to
      analyze the mechanisms involved in cGMP dynamics following retinal detachment.

PMID- 18334940
TI  - UV-A-induced structural and functional changes in human lens deamidated alphaB
      crystallin.
AB  - PURPOSE: To determine comparative effects of ultraviolet (UV)-A irradiation on
      structural and functional properties of wild type (WT) alphaB-crystallin and its
      three deamidated mutant proteins (alphaB-Asn78Asp, alphaB-Asn146Asp, and alphaB
      Asn78/146Asp). METHODS: Three deamidated mutants previously generated from
      recombinant WT alphaB-crystallin, using a site-specific mutagenesis procedure as
      previously described [32], were used. The WT alphaB-crystallin and its three
      deamidated species were exposed to UV-A light (320-400 nm) at intensities of 20
      or 50 J/cm(2). The UV-A-unexposed and UV-A-exposed preparations were examined for
      their chaperone activity, and their activities were correlated with the UV-A
      induced structural changes. The structural properties studied included
      dimerization and degradation, intrinsic tryptophan (Trp) fluorescence, ANS (8
      anilino-1-naphthalenesulfate)-binding, far ultraviolet circular dichroism (UV-CD)
      spectral analysis, molecular sizes by dynamic light scattering, and oxidation of
      Trp and methionine (Met) residues. RESULTS: The WT alphaB-crystallin and its
      three deamidated mutant proteins showed enhanced dimerization to 40 kDa species
      and partial degradation with increasing doses during UV-A-exposure. Compared to
      the deamidation of asparagines (Asn) 78 residue to aspartic acid (Asp) or both
      Asn78 and Asn146 residues to Asp, the deamidation of Asn146 residue to Asp
      resulted in a greater loss of chaperone activity. The UV-A-induced loss of
      chaperone activity due to structural changes was studied. The ANS-binding data
      suggested that the alphaB-Asn146Asp mutant protein had a relatively compact
      structure and an increase in surface hydrophobic patches compared to WT and two
      other deamidated proteins. Similarly, UV-A-exposure altered the Trp
      microenvironment in the deamidated mutant proteins compared to the WT alphaB
      crystallin. Far-UV CD spectral analyses showed almost no changes among WT and
      deamidated species on UV-A-exposure except that the alphaB-Asn146Asp mutant
      protein showed maximum changes in the random coil structure relative to WT alphaB
      crystallin and two other deamidated proteins. The UV-A-exposure also resulted in
      the aggregation of WT and the three deamidated mutant proteins with species of
      greater mass compared to the non-UV-A exposed species. Among the four spots
      recovered after two-dimensional (2D)-gel electrophoresis from WT and the three
      deamidated species, the Met and Trp residues of alphaB-Asn146Asp mutant showed
      maximum oxidation after UV-A exposure, which might account for its greater loss
      in chaperone activity compared to WT alphaB-crystallin and two other deamidated
      species. CONCLUSIONS: After UV-A-exposure, the deamidated alphaB-Asn146Asp mutant
      protein showed a complete loss of chaperone activity compared to WT alphaB and
      alphaB-Asn78Asp and alphaB-Asn78/146Asp deamidated species. Apparently, this loss
      of chaperone activity was due to oxidative changes leading to its greater
      structural alteration compared to other alphaB-species.

PMID- 18334941
TI  - Hypericin inhibits pathological retinal neovascularization in a mouse model of
      oxygen-induced retinopathy.
AB  - PURPOSE: Ocular neovascularization is a leading cause of blindness in ischemic
      retinopathies. Hypericin is an active ingredient in the medical herb St. John's
      Wort (SJW). Because hypericin inhibits intracellular signaling pathways that are
      believed to participate in the regulation of angiogenesis, we investigated the
      actions of hypericin and SJW in retinal neovascularization, using a mouse model
      of oxygen-induced retinopathy (OIR). METHODS: C57BL/6 neonatal mice were exposed
      to a 75% concentration of oxygen from postnatal day 7 (P7) to P12 and returned to
      room air from P12 to P17 to induce retinal neovascularization. SJW (15
      mg/kg/day), hypericin (15, 45, or 135 mug/kg/day), or vehicle was given by gavage
      once a day for five days from P12 to P17. To quantify the area of retinal
      neovascularization and vasoobliteration, we stained retinas with isolectin B4 at
      P17. Phosphorylation of extracellular signal-regulated kinase (ERK) in ischemic
      retinas was determined by western blot analysis. To estimate retinal
      vascularization, we stained retinas with isolectin B4 at P7 after treatment with
      SJW, hypericin, or vehicle from P3 to P7. RESULTS: Gavage administration of
      hypericin or SJW significantly inhibited the degree of retinal
      neovascularization, but did not affect the area of retinal vasoobliteration in a
      mouse model of OIR. Both SJW and hypericin had no effect on normal
      vascularization over the treatment time course. Treatment with SJW or hypericin
      reduced phosphorylation of ERK in the retina. CONCLUSIONS: These data suggest
      that hypericin and SJW reduce pathological retinal neovascularization and that
      administration of these agents could have clinical utility for treatment of
      ischemic retinopathies.

PMID- 18334942
TI  - Molecular analysis of ABCA4 and CRB1 genes in a Spanish family segregating both
      Stargardt disease and autosomal recessive retinitis pigmentosa.
AB  - PURPOSE: Stargardt disease (STGD), characterized by central visual impairment, is
      the most common juvenile macular dystrophy. All recessively inherited cases are
      thought to be due to mutations in the ABCA4 gene. Early-onset autosomal recessive
      retinitis pigmentosa (arRP) is a severe retinal degeneration that presents before
      the patient is ten years old. It has been associated with mutations in different
      genes, including CRB1. The aim of this study was to determine the genetic causes
      for two different retinal dystrophies, STGD and early-onset arRP, both
      segregating in one Spanish family. METHODS: Mutational analyses were performed
      using the ABCR400 and Leber congenital amaurosis (LCA) genotyping microarrays.
      Additional scanning for mutations was conducted by denaturing high performance
      liquid chromatography (dHPLC); results were confirmed by direct sequencing.
      RESULTS: A patient, who exhibited a STGD phenotype, was found to be homozygous
      for the p.Asn1805Asp (c.5413A>G) mutation in ABCA4. However, his affected sister,
      who had the arRP phenotype, was found to be heterozygous for this allele; no
      other sequence change could be found in ABCA4. Analysis using the LCA chip
      revealed the p.Cys948Tyr mutation in CRB1 in heterozygous state. A second
      mutation (p.Trp822ter) was found in the CRB1 gene in the affected female by
      denaturing high performance liquid chromatography (dHPLC) and direct sequencing.
      CONCLUSIONS: Two distinct retinal dystrophies with mutations affecting two
      different genes cosegregated in this family. The presence of two different
      phenotypes associated with mutations in two distinct genes in one single family
      must be considered especially when dealing with retinal dystrophies which bear
      high carrier frequencies in general population.

PMID- 18334943
TI  - Radiation cataracts: mechanisms involved in their long delayed occurrence but
      then rapid progression.
AB  - PURPOSE: This study was directed to assess the DNA damage and DNA repair response
      to X-ray inflicted lens oxidative damage and to investigate the subsequent
      changes in lens epithelial cell (LEC) behavior in vivo that led to long delayed
      but then rapidly developing cataracts. METHODS: Two-month-old C57Bl/6 female mice
      received 11 Grays (Gy) of soft x-irradiation to the head only. The animals' eyes
      were examined for cataract status in 30 day intervals by slit lamp over an 11
      month period post-irradiation. LEC migration, DNA fragment, free DNA retention,
      and reactive oxygen species (ROS) presence were established in the living lenses
      with fluorescent dyes using laser scanning confocal microscopy (LSCM). The extent
      and removal of initial LEC DNA damage were determined by comet assay.
      Immunohistochemistry was used to determine the presence of oxidized DNA and the
      response of a DNA repair protein in the lenses. RESULTS: This treatment resulted
      in advanced cortical cataracts that developed 5-11 months post-irradiation but
      then appeared suddenly within a 30 day period. The initially incurred DNA strand
      breaks were repaired within 30 min, but DNA damage remained as shown 72 h post
      irradiation by the presence of the DNA adduct, 8-hydroxyguanosine (8-OHG), and a
      DNA repair protein, XRCC1. This was followed months later by abnormal behavior by
      LEC descendant cells with abnormal differentiation and migration patterns as seen
      with LSCM and fluorescent dyes. CONCLUSIONS: The sudden development of cortical
      cataracts several months post-irradiation coupled with the above findings
      suggests an accumulation of damaged descendants from the initially x-irradiated
      LECs. As these cells migrate abnormally and leave acellular lens surface sites,
      eventually a crisis point may arrive for lens entry of environmental O(2) with
      resultant ROS formation that overwhelms protection by resident antioxidant
      enzymes and results in the coagulation of lens proteins. The events seen in this
      study indicate the retention and transmission of progenitor cell DNA damage in
      descendant LEC. The cellular and molecular events parallel those previously
      reported for LSCM observations in age-related cataracts.

PMID- 18334944
TI  - Keratocyte phenotype is enhanced in the absence of attachment to the substratum.
AB  - PURPOSE: Keratocytes, mesenchymal cells populating the corneal stroma, secrete
      the unique transparent connective tissue of the cornea as well as opaque scar
      tissue after injury. Previous studies identified factors mediating keratocyte
      phenotype in vitro, particularly the expression of the keratan sulfate
      proteoglycans, which are essential for vision. Whereas earlier work emphasized
      effects of cytokines, the current study examines the effects of substratum
      attachment on keratocyte phenotype. METHODS: Primary keratocytes from collagenase
      digestion of bovine corneas were cultured on tissue-culture plastic or on poly (2
      hydroxyethylmethacrylate)(polyHEMA)-coated, non-adhesive surfaces. Secreted
      proteoglycans from culture media and cell-associated proteins were characterized
      using western blotting or isotopic labeling. Gene expression was characterized
      with quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).
      Secreted matrix was examined with immunostaining. RESULTS: We observed that
      virtually all primary keratocytes participate in the formation of spheroidal
      aggregates, remaining viable for at least four weeks in vitro. Spheroid
      keratocytes secrete more keratan sulfate and keratocan than attached cells in the
      same culture medium. In spheroids, keratocytes accumulate substantial matrix in
      intercellular spaces, including keratan sulfate, lumican, keratocan, and
      collagens V and VI. The unattached cells undergo limited cell division and do not
      differentiate into myofibroblasts in response to transforming growth factor beta
      (TGFbeta), which is based on the expression of extra domain A (EDA) fibronectin
      and alpha-smooth muscle actin. Similarly, the platelet derived growth factor, a
      cytokine initiating the fibroblastic phenotype in attached keratocytes, had a
      limited effect on the spheroid-associated keratocytes. Ascorbate-2-phosphate was
      the only agent stimulating keratan sulfate secretion in the spheroid keratocytes.
      CONCLUSIONS: These results provide a new paradigm for understanding signals that
      regulate extracellular matrix secretion. For primary keratocytes, the alteration
      of the cellular environment in terms of cell-cell and cell-matrix interactions
      mediates and can override signals from soluble cytokines in influencing matrix
      expression and also in adopting other aspects of the fibroblastic and
      myofibroblastic phenotypes found in healing wounds.

PMID- 18334945
TI  - Endothelial nitric oxide synthase gene T-786C and 27-bp repeat gene polymorphisms
      in retinopathy of prematurity.
AB  - PURPOSE: Retinopathy of prematurity (ROP), which is associated with abnormal
      retinal vessel development, is the leading cause of visual loss in preterm
      infants. Endothelial nitric oxide synthase (eNOS) is believed to play a central
      role in both retinal angiogenesis and vasculogenesis. The aim of this study was
      to investigate functional genetic polymorphisms of eNOS in the pathogenesis of
      ROP. METHODS: eNOS T(-786)C and 27-bp repeat (eNOS, b: wild-type, a: mutant)
      genotypes were determined using allele-specific polymerase chain reaction in 105
      low birth weight (LBW) preterm infants treated for ROP (treated group). A control
      group was set up and composed of 127 LBW infants with stage 1 or 2 ROP that did
      not not require treatment (untreated group). RESULTS: The genotype distribution
      of eNOS 27-bp repeat polymorphism was found to significantly differ (p=0.015)
      between the two groups, whereas the genotype distribution of eNOS T(-786)C did
      not differ (p=0.984) between the groups. There was no difference in the
      distribution of either the "a" allele (p=0.153) nor of the C allele (p=0.867) in
      a groups comparison. Multiple logistic regression analysis revealed that male
      gender (p=0.046) and eNOS aa genotype (p=0.047 versus ab genotype and p=0.022
      versus bb genotype) were significantly associated severe ROP that required
      treatment. The haplotype estimations based on the detected genotype distributions
      showed that the prevalence of aT and bT haplotypes was significantly increased in
      the group treated for ROP. CONCLUSIONS: Functional eNOS 27-bp repeat polymorphism
      might be associated with the risk of severe ROP, however we found no association
      between the eNOS T(-786)C and the pathogenesis of ROP.

PMID- 18334946
TI  - A novel mutation in GJA8 associated with jellyfish-like cataract in a family of
      Indian origin.
AB  - PURPOSE: To identify the underlying genetic defect in a three-generation family
      with five members affected with dominant bilateral congenital cataract and
      microcornea. METHODS: Detailed family history and clinical data were recorded.
      Mutation screening in the candidate genes, CRYAA, CRYBB1, MAF, GJA3, and GJA8,
      was performed by bidirectional sequencing of the amplified products. RESULTS:
      Affected individuals had a jellyfish-like cataract in association with
      microcornea. Sequencing of GJA8 (connexin 50) showed a novel, heterozygous c.134G
      ->C change that resulted in the substitution of a highly conserved tryptophan by
      serine (p.W45S). This sequence change segregated completely with the disease
      phenotype and was not observed in 108 ethnically matched controls (216
      chromosomes). However, an identical substitution has previously been described in
      GJA3 (connexin 46) leading to autosomal dominant nuclear cataract without
      microcornea. CONCLUSIONS: This is a novel mutation identified in the first
      transmembrane domain (M1) of GJA8. These findings further expand the mutation
      spectrum of connexin 50 (Cx50) in association with congenital cataract and
      microcornea.

PMID- 18334947
TI  - Association of non-synonymous single nucleotide polymorphisms in the LOXL1 gene
      with pseudoexfoliation syndrome in India.
AB  - PURPOSE: In the Icelandic and Swedish populations, pseudoexfoliation syndrome
      (XFS) and pseudoexfoliation glaucoma (XFG) has been significantly associated with
      LOXL1 exon 1 polymorphisms - allele G of rs1048661 (R141L) and allele G of
      rs3825942 (G135D). In this study, we looked at the association of rs1048661 and
      rs3825942 in a southern Indian population. METHODS: Fifty-two cases with XFS
      (including XFG) and 97 matched controls that had thorough glaucoma evaluations
      were included in the study. Exon 1 of the LOXL1 gene with the single nucleotide
      polymorphisms (SNPs) were amplified and sequenced. For statistical significance,
      Pearson's Chi(2) test was performed. The HAPLOVIEW program v4.0 was used to
      determine the Hardy-Weinberg equilibrium and haplotype association. RESULTS: In
      our study population, there was a significant association of allele G of
      rs3825942 with XFS (p=0.0001) and genotype GG (p=0.000305) with XFS. CONCLUSIONS:
      Out of the two non-synonymous SNPs in exon 1 of the LOXL1 gene, rs3825942 has a
      significant association with XFS cases in the patients of the southern Indian
      population. To the best of our knowledge, this is the first Asian study
      replicating the European studies.

PMID- 18334948
TI  - Mass spectrometry-based proteomic analyses of contact lens deposition.
AB  - PURPOSE: The purpose of this report is to describe the contact lens deposition
      proteome associated with two silicone hydrogel contact lenses and care solutions
      using a mass spectrometric-based approach. METHODS: This was a randomized,
      controlled, examiner-masked crossover clinical trial that included 48
      participants. Lenses and no-rub care solutions evaluated included galyfilcon A
      (Acuvue Advance, Vistakon Inc., Jacksonville, FL), lotrafilcon B (O2 Optix, CIBA
      Vision Inc., Duluth, GA), AQuify (CIBA Vision Inc.), and ReNu MoistureLoc (Bausch
      and Lomb Inc., Rochester, NY). After two weeks of daily wear in each lens
      solution combination, the left lens was removed by the examiner (using gloves and
      forceps) and placed in a protein precipitation buffer (acetone). The precipitate
      was quantitated for total protein concentration (per lens), and proteins were
      then identified using liquid chromatography tandem mass spectrometry (nano-LC
      MS/MS) and peptide sequencing. RESULTS: Between 7.32 and 9.76 microg/lens of
      protein was observed on average from each lens-solution combination. There were
      19 total unique proteins identified across the two lens materials, and six
      proteins were identified in all four lens-solution combinations including
      lipocalin, lysozyme, lacritin, lactoferrin, proline rich 4, and Ig Alpha.
      Lotrafilcon B was associated with 15 individual proteins (across both care
      solutions), and 53% of these proteins were observed in at least 50% of the
      analyses. Galyfilcon A was associated with 13 individual proteins, and 38.5% of
      these proteins were observed in at least 50% of the analyses. There were three
      unique proteins identified from galyfilcon A and four unique proteins identified
      from lotrafilcon B. CONCLUSIONS: The total amount of proteins identified from
      silicone hydrogel materials is much less than the amount from traditional soft
      lens materials. For the most part, the deposition proteome across these lenses is
      similar, although the different polymer characteristics might be associated with
      some variability in observance of the less frequently identified proteins.

PMID- 18334949
TI  - Proteomic analysis of aqueous humor from patients with myopia.
AB  - PURPOSE: The mechanism of axial elongation in the myopic eyeball remains to be
      elucidated. It is known that the expression profile for some proteins in the
      aqueous humor (AH) changes in some diseases. Accordingly, determinations of these
      AH proteins may serve to understand their potential role in this pathogenesis. To
      identify the possible mechanism in myopia development, a proteomic analysis of
      the AH composition from high myopic eyes (patients) was performed and compared
      with that of the AH composition from non-myopic cataract eyes (controls).
      METHODS: Total protein concentration in AH was determined by the Bradford method,
      and separation profiles were analyzed by two-dimensional (2D) gel
      electrophoresis. Protein in gel was determined by silver stain, and the
      separation profiles were analyzed to assess spot density changes between myopia
      and non-myopia patients. These spots in gel were isolated and identified by mass
      spectrometry. RESULTS: The total protein concentration in AH with high myopia was
      significantly greater than that of non-myopia. A total of six spots were
      significantly increased in 2D gels from high myopia. The spots were derived from
      albumin, transthyretin, and a vitamin D-binding protein. CONCLUSIONS: The protein
      composition in AH was significantly different between myopia and non-myopia. The
      identified proteins could be a potential biomarker for high myopia development
      and may play a role in the mechanisms of myopia ocular axial elongation.

PMID- 18334950
TI  - The influence of visible light exposure on cultured RGC-5 cells.
AB  - PURPOSE: To determine the effects of visible light on normal or metabolically
      compromised cultured rat RGC-5 cells. METHODS: Cultured RGC-5 cells were exposed
      to different durations as well as intensities of optical radiation, filtered to
      exclude wavelengths below 400 nm. Some cells were also subjected to metabolic
      compromise by depriving them of serum (serum deprivation; SD). Treated cells were
      assayed for cell viability using the 3,(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) reduction assay, for DNA breakdown by terminal
      deoxynucleotidyl transferase (TdT)-mediated d-UTP-linked nick end labeling
      (TUNEL), apoptotic protein activation by immunoblotting, and the production of
      reactive oxygen species (ROS) with dihydroethidium. A subset of cells was treated
      with 100 pM rotenone as an alternative means to induce metabolic stress; this was
      to determine that the influence of light on compromised cells was not specific to
      serum-deprivation alone. RESULTS: Exposure to the light for 48 h activated both
      caspase-3 and Bcl-associated X-protein (Bax) in cultured RGC-5 cells.
      Furthermore, light (1000 or 4000 lux), SD, and rotenone caused minor but
      significant decreases in cellular MTT reduction. SD and light also led to
      cellular DNA breakdown, although only light caused ROS production. Light (48 h)
      significantly exacerbated the effect of SD on MTT reduction and DNA cleavage.
      Furthermore, the antioxidant, trolox, significantly blunted the detrimental
      influence of light on cell viability, increase in TUNEL-positive cells, and the
      generation of ROS. CONCLUSIONS: Exposure to light was slightly, but
      significantly, harmful to healthy RGC-5 cells alone, but was much more toxic to
      those cells that were energetically compromised. Continuous light exposure can
      therefore detrimentally affect metabolically stressed RGC-5 cells. This may have
      implications for some ocular retinopathies such as glaucoma.

PMID- 18334952
TI  - Identification of differentially expressed genes in carp rods and cones.
AB  - PURPOSE: Rods and cones differ in their photoresponse characteristics,
      morphology, and susceptibilities to certain diseases. To contribute to the
      studies at the molecular level of these differences, we tried to identify genes
      expressed preferentially in rods or cones. METHODS: From purified carp rods and
      cones, we extracted their RNA and obtained corresponding cDNA pools (rod cDNA and
      cone cDNA). We employed the suppression subtractive hybridization method to
      identify the genes expressed preferentially in rods or cones. Cone cDNA was
      subtracted from rod cDNA to obtain cDNA, which ideally contained cDNA expressed
      preferentially in rods (R/c cDNA). Similarly, rod cDNA was subtracted from cone
      cDNA to obtain C/r cDNA. With differential array screening, we screened candidate
      genes that were expressed mainly or exclusively in rods or cones. The nucleotide
      sequences of the positive genes were determined. In some of them, their mRNA
      localizations were confirmed by in situ hybridization. RESULTS: R/c cDNA
      contained genes already known to code rod specific proteins, such as cGMP gated
      channel, transducin beta1, and rhodopsin. In sharp contrast, C/r cDNA contained
      genes that code proteins of which functions are mostly unknown. Among them, N-myc
      downregulated gene 1-like (NDRG1L) and aryl hydrocarbon receptor 2 (AhR2) were
      most abundant, and by in situ hybridization, they were proven to be expressed
      specifically in cones. CONCLUSIONS: Using purified rods and cones, we identified
      mRNAs expressed preferentially in rods or cones. Of particular interest is the
      specific expression of NDRG1L and AhR2 in cones.

PMID- 18334951
TI  - Neutralizing antibody to VEGF reduces intravitreous neovascularization and may
      not interfere with ongoing intraretinal vascularization in a rat model of
      retinopathy of prematurity.
AB  - PURPOSE: To study the effects of a neutralizing antibody to vascular endothelial
      growth factor (VEGF), given as an intravitreous injection, on intravitreous
      neovascularization (IVNV) and ongoing vascular development of avascular retina in
      a rat model relevant to human retinopathy of prematurity. METHODS: Newborn
      Sprague-Dawley rats were exposed to oxygen fluctuations alternating between 50%
      O(2) and 10% O(2) every 24 h. At postnatal day (p)12, rat pups received
      intravitreous injections of a neutralizing antibody to VEGF or control nonimmune
      rat IgG in one eye and were returned to oxygen cycling until p14, at which time
      they were placed into room air. At p18 (time of maximal IVNV) or p25 (time point
      in regression), animals were sacrificed. Their retinas were dissected, flat
      mounted, and stained with Alexa-isolectin for fluorescence microscopy. IVNV was
      measured as number of clock hours involved in injected VEGF antibody and control
      eyes. Mean clock hours of IVNV, avascular/total retinal areas and capillary
      densities within vascularized retinas were determined in injected eyes of control
      and treatment groups. Mean clock hours of IVNV in fellow noninjected eyes from
      control and treatment groups were analyzed by Student's t-tests to assess
      possible crossover effects from systemic absorption of antibody. Eyes from p13
      rat pups were sectioned for immunohistochemistry or analyzed for VEGF receptor 2
      (VEGFR2) phosphorylation by western blot. Free retinal VEGF at p13, one day
      following injections, was measured by ELISA. RESULTS: Neutralizing antibody to
      VEGF at 25 ng and 50 ng caused a modest but significant inhibition of IVNV
      compared to IgG injected controls at p18, but only the 50 ng dose decreased IVNV
      compared to control at p25 (one-way ANOVA p=0.003; posthoc Bonferroni t-test
      p=0.003). Neither dose caused a significant difference in avascular/total retinal
      area at p18 compared to control. However, at p25, the 50 ng dose caused a
      significant reduction in avascular/total retinal area compared to the 25 ng dose
      (ANOVA p=0.038; posthoc Student's t-test p=0.038). There was no difference in
      avascular/total retinal area between IgG and the 25 ng dose. At p13, qualitative
      analysis of immunohistochemical sections of retina showed the 50 ng dose of VEGF
      antibody reduced VEGFR2 phosphorylation within the retina and around blood
      vessels. Also at p13, there was a significant increase in free intraretinal VEGF
      protein in eyes that had been treated with 50 ng dose of VEGF antibody compared
      to IgG injected control (Student's t-test p=0.042). There were no differences in
      capillary densities in the vascularized retinas between eyes injected with the 50
      ng dose of VEGF antibody and IgG control. There was also no difference in weight
      gain between treated and control groups. CONCLUSIONS: Neutralizing antibody to
      VEGF at a 50 ng dose caused a significant and sustained reduction in IVNV without
      interfering with ongoing retinal vascularization in a rat model of ROP, whereas a
      lower dose of antibody did not. These data also suggest that compensatory
      regulatory mechanisms may lead to increased VEGF concentration after
      intravitreous injection of a neutralizing antibody to VEGF. Further study is
      necessary for safety and for determination of drug dose of VEGF antibody, since
      dose of treatment appears important and may vary among infants with severe ROP.
      In this study, survival of already developed retinal capillaries did not appear
      affected. Neutralizing VEGF by an intravitreous injection of antibody may offer a
      treatment consideration for severe ROP, which fails current standard of care
      management.

PMID- 18334953
TI  - Mutation G61C in the CRYGD gene causing autosomal dominant congenital coralliform
      cataracts.
AB  - PURPOSE: We sought to identify the genetic defect in a four-generation Chinese
      family with autosomal dominant congenital coralliform cataracts and demonstrate
      the functional analysis of a candidate gene in the family. METHODS: Family
      history data were recorded. Clinical and ophthalmologic examinations were
      performed on affected and unaffected family members. All the members were
      genotyped with microsatellite markers at loci considered to be associated with
      cataracts. Two-point LOD scores were calculated using the Linkage software after
      genotyping. A mutation was detected by direct sequencing, using gene-specific
      primers. Wild-type and mutant proteins were analyzed with online software.
      RESULTS: Affected members of this family had coralliform cataracts. Linkage
      analysis was obtained at markers, D2S72 (LOD score [Z]=3.31, recombination
      fraction [theta]=0.0) and D2S1782 (Z=3.01, theta=0.0). Haplotype analysis
      indicated that the cataract gene was closely linked to these two markers.
      Sequencing the gammaD-crystallin gene (CRYGD) revealed a G>T transversion in exon
      2, which caused a conservative substitution of Gly to Cys at codon 61 (P.G61C).
      This mutation co-segregated with the disease phenotype in all affected
      individuals and was not observed in any of the unaffected or 100 normal,
      unrelated individuals. Bioinformatic analyses showed that a highly conserved
      region was located around Gly61. Data generated with online software revealed
      that the mutation altered the protein's stability, solvent-accessibility, and
      interactions with other proteins. CONCLUSIONS: This is the first reported case of
      a congenital coralliform cataract phenotype associated with the mutation of
      Gly61Cys (P.G61C) in the CRYGD gene; it demonstrates a possible mechanism of
      action for the mutant gene.

PMID- 18334954
TI  - A penetrating ocular injury can affect the induction of anterior chamber
      associated immune deviation.
AB  - PURPOSE: To determine the effect of penetrating ocular injury on the induction of
      anterior chamber-associated immune deviation (ACAID). METHODS: An injection of 5
      mul ovalbumin (OVA, 20 mg/ml) into the anterior chamber (AC) of female BALB/c
      mice was performed to induce ACAID. A penetrating ocular injury was induced via
      the limbus on OVA-inoculated eyes at 24 h, 48 h, 72 h, and 120 h following AC
      injection. The mice receiving an OVA inoculation without the ocular injury served
      as the AC-injection group. Delayed type hypersensitivity (DTH) was examined to
      evaluate the induction of ACAID. The levels of transforming growth factor (TGF)
      beta1, interleukin (IL)-10, and interferon (IFN)-gamma produced by splenocytes
      were detected by enzyme-linked immunosorbent assays (ELISA). The frequency of
      CD4(+)CD25(+)Foxp3(+)T cells in the splenocytes was detected by flow cytometry.
      RESULTS: A significantly decreased DTH response was observed in the AC-injection
      group as well as in mice that received a penetrating injury at 72 h and 120 h
      following AC-injection of OVA. The levels of TGF-beta1 and IL-10 produced by
      splenocytes of mice in the AC-injection group and in the 72-h and 120-h group
      were significant higher than those in the 24-h and 48-h group. However, the
      levels of IFN-gamma produced by splenocytes of the AC-injection group and the 72
      h and 120-h group were significantly lower than those in the 24-h and 48-h group.
      An increased frequency of CD4(+)CD25(+)Foxp3(+)T cells was found in the AC
      injection group and the 72-h and 120-h group. CONCLUSIONS: Penetrating ocular
      injury preformed shortly (24 h-48 h) after an AC injection of an antigen was able
      to abrogate ACAID and was associated with a decreased production of TGF-beta1 and
      IL-10, an increased production of IFN-gamma, and a decreased expression of
      CD4(+)CD25(+)Foxp3(+)T cells.

PMID- 18334955
TI  - Common MFRP sequence variants are not associated with moderate to high hyperopia,
      isolated microphthalmia, and high myopia.
AB  - PURPOSE: The membrane-type frizzled-related protein (MFRP) gene is selectively
      expressed in the retinal pigment epithelium and ciliary body, and mutations of
      this gene cause nanophthalmos. The MFRP gene may not be essential for retinal
      function but has been hypothesized to play a role in ocular axial length
      regulation. The involvement of the MFRP gene in moderate to high hyperopic,
      isolated microphthalmic/anophthalmic, and high myopic patients was tested in two
      phases: a mutation screening/sequence variant discovery phase and a genetic
      association study phase. METHODS: Eleven hyperopic, ten
      microphthalmic/anophthalmic, and seven non-syndromic high-grade myopic patients
      of varying ages and 11 control subjects participated in the mutation screening
      phase. Sixteen primer pairs were designed to amplify the 13 exons of the MFRP
      gene including intron/exon boundaries. Polymerase chain reactions were performed,
      and amplified products were sequenced using standard techniques. Normal and
      affected individual DNA sequences were compared alongside the known reference
      sequence (UCSC genome browser) for the MFRP gene. The genetic association study
      included 146 multiplex non-syndromic high-grade myopia families. Seventeen
      intragenic and flanking single nucleotide polymorphisms (SNPs) were chosen for
      the MFRP gene and genotyped in the large data set using the Taqman allelic
      discrimination assay. The family-based association Pedigree Disequilibrium Test
      (PDT) and GenoPDT were performed. RESULTS: The average spherical refractive error
      of the hyperopic patient cohort was +4.21 diopters (D; range +2.00 to +9.25 D)
      and of the myopic patient cohort was -12.36 D (range -8.25 to -14.50 D). A total
      of 16 SNPs were identified by direct sequencing. No significant association was
      determined between the 16 MFRP gene SNPs and the moderate to high hyperopia,
      microphthalmia/anophthalmia affection status, and high myopia. Family based
      association analysis did not reveal any association between the 17 SNPs genotyped
      in the larger family data set for any refractive error type. CONCLUSIONS:
      Sequence variants of the MFRP gene do not appear to be associated with either the
      less severe forms of hyperopia, extreme forms of limited eye growth and
      development, or high myopia. These results indicate that the MFRP gene may not
      play a role in regulating ocular axial length in these phenotypes.

PMID- 18334956
TI  - Comparative study on the cytotoxic effects of benzalkonium chloride on the Wong
      Kilbourne derivative of Chang conjunctival and IOBA-NHC cell lines.
AB  - PURPOSE: The Wong-Kilbourne derivative of Chang conjunctiva-derived cell line has
      been widely used for toxicological and functional in vitro studies on the ocular
      surface. The common reserve to this cell line is the reported contamination with
      HeLa cells. Thus, the IOBA-NHC spontaneously immortalized conjunctival epithelial
      cell line has been recently developed and did not show other cell type
      contamination. Our purpose was to determine whether both cell lines would be
      equally suitable for in vitro toxicological studies. Therefore, we compared in
      these two cell types the toxic effects of the preservative, benzalkonium chloride
      (BAC); its toxicity has been often reported on conjunctival in vivo and in vitro
      models. METHODS: The necrotic, apoptotic, and oxidative effects of BAC were
      evaluated on Chang and IOBA-NHC cell lines using microplate cytofluorometry tests
      (neutral red, 2,7- dichlorofluorescein diacetate dye [H(2)DCF-DA], hydroethidine,
      and Yopro-1), flow cytometry (Annexin V/7-AAD and DNA content tests), and
      standard immunofluorescence stainings. Cells were exposed to five concentrations
      of BAC (10(-2)%, 5.10(-3)%, 10(-3)%, 10(-4)%, and 10(-5)%) for two incubation
      times: 15 min of treatment and 15 min of treatment followed by 24 h of cell
      recovery in complete medium. RESULTS: All parameters of toxicity increased in a
      BAC dose-dependent manner on both cell lines. CONCLUSIONS: The comparison of BAC
      toxicity on both cell lines supported the use of IOBA-NHC and Chang cells for
      toxicological in vitro studies. Drawbacks of both cell lines have to be known and
      considered in studies performed on these cell lines.

PMID- 18334958
TI  - Investigation of the human tear film proteome using multiple proteomic
      approaches.
AB  - PURPOSE: The purpose of this work was to examine the tear film proteome using a
      combination of one-dimensional (1D) and two dimensional (2D) gel electrophoresis
      and mass spectrometry-based techniques and to explore the effect of the tear
      collection methods on the tear proteome. METHODS: Tear samples from eight normal
      non-contact lens wearing human subjects collected by Drummond glass
      microcapillary and Schirmer strips were subjected to 1D-sodium dodecyl sulfate
      polyacrylamide gel electrophoresis (SDS-PAGE), 2D-SDS-PAGE, and 2D LC-MS/MS
      (Multidimensional protein identification technology - MudPIT). Bands or cores
      from the 1D- and 2D-SDS-PAGE were cut, digested with trypsin, and analyzed by
      tandem mass spectrometry for identification by the generation of sequence tags.
      RESULTS: In total (across sampling and proteomic methods), 97 unique proteins
      were observed, and a significant number of the spots/bands in the PAGE were from
      posttranslational modifications. Fifty-four unique proteins were identified from
      proteins extracted from the Schirmer strips in comparison to 13 unique proteins
      identified from capillary tubes, and 30 unique proteins were identified by both
      collection methods. Secreted (serum) proteins were predominantly observed from
      tears collected by capillary whereas a combination of cellular and serum proteins
      were identified from tear film collected by Schirmer strips. CONCLUSIONS:
      Overall, these results suggest that the tear film collection and the proteomic
      method impacts the proteins present in the tear film and that care should be
      exercised in choosing a tear collection method to best correlate to the
      experiment being conducted or the hypothesis that is being tested.

PMID- 18334957
TI  - Robust hypoxia-selective regulation of a retinal pigment epithelium-specific
      adeno-associated virus vector.
AB  - PURPOSE: To develop an hypoxia-regulated retinal pigment epithelium (RPE)
      specific adeno-associated virus (AAV) gene transfer platform that exploits
      hypoxia as a physiologic trigger for an early antiangiogenic treatment strategy
      directed at arresting neovascularization in the eye. METHODS: Tissue-specific and
      hypoxia-regulated expression vectors were constructed with tandem combinations of
      hypoxia responsive elements and aerobically silenced elements (HRSE) that
      together induce gene expression in hypoxia and suppress it in normoxia. For RPE
      specific expression, the HRSE and a (6x) HRE (hypoxia responsive element)
      oligomer were ligated upstream of the Rpe65 promoter in a pGL3 firefly luciferase
      plasmid (pGL3-HRSE-6xHRE-Rpe65). The cell specificity of this novel hybrid
      promoter was tested in human RPE (ARPE-19), human glioblastoma, rat C6 glioma,
      mouse hippocampal neurons, and human embryonic kidney cell lines. Expression of
      all cell types in normoxia, and following 40 h hypoxia, was analyzed by dual
      luciferase assay. After confirmation of its tissue-specificity and hypoxia
      inducibility, the hybrid promoter construct was integrated into a replication
      deficient AAV delivery system and tested for cell-selectivity and hypoxia
      inducible green fluorescent protein (GFP) reporter expression. RESULTS: The HRSE
      6xHRE-Rpe65 promoter was highly selective for RPE cells, strongly induced in
      hypoxia, and similar in activation strength to the cytomegalovirus (CMV)
      promoter. The AAV.HRSE.6xHRE.Rpe65 vector induced robust GFP expression in
      hypoxic ARPE-19 cells, but elicited no GFP expression in hypoxia in other cell
      types or in normoxic ARPE-19 cells. CONCLUSIONS: The hypoxia-regulated,
      aerobically-silenced RPE-targeting vector forms a platform for focal
      autoregulated delivery of antiangiogenic agents in hypoxic regions of the RPE.
      Such autoinitiated therapy provides a means for early intervention in choroidal
      neovascularization, when it is most sensitive to inhibition.

PMID- 18334959
TI  - Identification of a novel splice-site mutation in the Lebercilin (LCA5) gene
      causing Leber congenital amaurosis.
AB  - PURPOSE: Leber congenital amaurosis (LCA) is one of the most common causes of
      hereditary blindness in infants. To date, mutations in 13 known genes and at two
      other loci have been implicated in LCA causation. An examination of the known
      genes highlights several processes which, when defective, cause LCA, including
      photoreceptor development and maintenance, phototransduction, vitamin A
      metabolism, and protein trafficking. In addition, it has been known for some time
      that defects in sensory cilia can cause syndromes involving hereditary blindness.
      More recently evidence has come to light that non-syndromic LCA can also be a
      "ciliopathy." METHODS: Here we present a homozygosity mapping analysis in a
      consanguineous sibship that led to the identification of a mutation in the
      recently discovered LCA5 gene. Homozygosity mapping was done using Affymetrix 10K
      Xba I Gene Chip and a 24.5cM region on chromosome 6 (6q12- q16.3) was identified
      to be significantly homozygous. The LCA5 gene on this region was sequenced and
      cDNA sequencing also done to characterize the mutation. RESULTS: A c.955G>A
      missense mutation in the last base of exon 6 causing disruption of the splice
      donor site was identified in both the affected sibs. Since there is a second
      consensus splice donor sequence 5 bp into the adjacent intron, this mutation
      results in a transcript with a 5 bp insertion of intronic sequence, leading to a
      frameshift and premature truncation. CONCLUSIONS: We report a missense mutation
      functionally altering the splice donor site and leading to a truncated protein.
      This is the second report of LCA5 mutations causing LCA. It may also be
      significant that one affected child died at eleven months of age due to asphyxia
      during sleep. To date the only phenotype unambiguously associated with mutations
      in this gene is LCA. However the LCA5 gene is known to be expressed in
      nasopharynx, trachea and lungs and was originally identified in the proteome of
      bronchial epithelium ciliary axonemes. The cause of death in this child may
      therefore imply that LCA5 mutations can in fact cause a wider spectrum of
      phenotypes including respiratory disease.

PMID- 18334960
TI  - Mesenchymal cells from limbal stroma of human eye.
AB  - PURPOSE: Mesenchymal stem cells (MSC) are self-renewing, multipotent cells that
      are present in many adult tissues, including bone marrow, trabecular bone,
      adipose, and muscle. The presence of such cells of mesenchymal origin and their
      role during the wound healing of ocular injuries are currently being explored by
      many studies worldwide. In this study, we aimed to report the presence of
      mesenchymal cells resembling bone marrow-derived cells (MSC-BM) in the limbus of
      the human eye. METHODS: Fresh limbal tissues obtained from human subjects
      undergoing limbal biopsy for ocular surface reconstruction were used to establish
      limbal mesenchymal cell (MC-L) cultures. The spindle cell outgrowths observed in
      extended limbal epithelial cultures (LECs) and from deepithelialized limbal
      tissues were serially passaged using a human corneal epithelial (HCE) medium,
      which contained epidermal growth factor (EGF) and insulin, and supplemented with
      fetal bovine serum (FBS). MSC cultures were established from human bone marrow
      samples using Dulbecco's Modified Eagles Medium (DMEM) supplemented with FBS. The
      mesenchymal cells from both extended limbal cultures (MC-L) and bone marrow (MSC
      BM) were characterized by morphology and immunophenotyping using epithelial,
      mesenchymal, hematopoietic, and endothelial markers using fluorescent-activated
      cell sorting (FACS). Selective markers were further confirmed by immunostaining
      and reverse transcription polymerase chain reaction (RT-PCR). Stromal cells of
      both origins (limbal and bone marrow-derived) were also evaluated for colony
      forming ability and population doubling. Attempts were made to differentiate
      these into adipocytes and osteocytes using conditioned medium. RESULTS: Spindle
      cells from extended limbal epithelial cultures as well as de-epithelialized human
      limbal tissues appeared elongated and fibroblast-like with oval vesicular nuclei.
      Both MC-L and MSC-BM showed colony forming ability in 14 days of plating. MC-L
      showed a population doubling of 22.95 while in MSC-BM, it was 30.98.
      Immunophenotyping of these cells by FACS and immunocytochemistry showed that the
      MC-L were positive for mesenchymal markers and negative for epithelial and
      hematopoietic markers similar to MSC-BM. The MC-L phenotype has thus been defined
      as MC-L(CD105, CD106, CD54, CD166, CD90, CD29, CD71, pax -6 +/ p75, SSEA1, Tra-1
      61, Tra-1-81, CD31, CD34, CD45, CD11a, CD11c, CD14, CD138, Flk1, Flt1, VE
      Cadherin -). The profile was further confirmed by RT-PCR. These cells also showed
      differentiation into adipocytes and osteocytes. CONCLUSIONS: We demonstrated the
      presence of mesenchymal cells in the human limbus, similar to the bone marrow
      derived MSC-BM. This presence suggests that these cells are unique to the adult
      stem cell niche.

PMID- 18334961
TI  - Expression of K6W-ubiquitin in lens epithelial cells leads to upregulation of a
      broad spectrum of molecular chaperones.
AB  - PURPOSE: Accumulation and precipitation of abnormal proteins are associated with
      many age-related diseases. The ubiquitin-proteasome pathway (UPP) is one of the
      protein quality control mechanisms that selectively degrade damaged or obsolete
      proteins. The other arm of the protein quality control mechanism is molecular
      chaperones, which bind to and help refold unfolded or misfolded proteins. We
      previously showed that the molecular chaperones and the UPP work in a competitive
      manner in eliminating the denatured proteins. To further investigate the
      interaction between the two protein quality control mechanisms, we determined the
      effects of the impairment of the UPP on the expression of molecular chaperones in
      human lens epithelial cells (HLEC). METHODS: K6W-ubiquitin, a dominant negative
      inhibitor of the UPP, was expressed in confluent HLEC via an adenoviral vector.
      The mRNA levels of cytoplasmic and endoplasmic reticulum (ER) chaperones were
      determined by real-time reverse transcription polymerase chain reaction (RT-PCR).
      Protein levels for these chaperones were determined by western blotting. RESULTS:
      Expression of K6W-ubiquitin in HLEC increased the expression of a broad spectrum
      of molecular chaperones. Among the heat-shock proteins, mRNA for alphaB
      crystallin, Hsp70, and Hsp90 increased 27 fold, 21 fold, and twofold,
      respectively, in response to K6W-ubiquitin expression. Among the ER chaperones
      and ER stress related factors, mRNA levels of protein disulfide isomerase, Grp75,
      Grp78, Grp94, and the CAAT/enhancer binding protein homologous protein (CHOP)
      increased from 1.7 fold to 3.7 fold. The mRNA for Hsp60 also increased 1.6 fold
      in response to the expression of K6W-ubiquitin. The expression pattern of these
      chaperones in response to the expression of K6W ubiquitin is similar to that
      obtained when cells were treated with proteasome inhibitors or heat-shock.
      CONCLUSIONS: It appears that the upregulation of these chaperones is related to
      the elevated levels of abnormal proteins in the cells. These findings support our
      hypothesis that the molecular chaperones and the UPP may back each other up in
      the process of protein quality control. The upregulation of molecular chaperones
      in response to the expression of a dominant negative ubiquitin may compensate for
      the impairment of the UPP in the degradation of abnormal proteins.

PMID- 18334962
TI  - Presence of myocilin sequence variants in Japanese patients with open-angle
      glaucoma.
AB  - PURPOSE: To examine the myocilin (MYOC) gene for mutations in Japanese patients
      with primary open-angle glaucoma (POAG) and to determine the phenotypes of the
      patients with the mutations. METHODS: One-hundred thirty-eight unrelated Japanese
      patients with POAG were studied. Genomic DNA was extracted from leukocytes of
      peripheral blood, and the three coding exons including the intron-exon boundaries
      were amplified by polymerase chain reaction (PCR) and directly sequenced bi
      directionally. RESULTS: Two sequence variants were identified, one novel non
      synonymous amino acid change (p.Gln297His) and one reported synonymous amino acid
      change (p.Ala363Thr). These mutations were not detected in the 118 ethnically
      matched controls. p.Gln297His was found in a 70-year-old man, who developed POAG
      at a late age, and his intraocular pressure was high. p.Ala363Thr was found in
      two cases, and both patients developed POAG at an early age and had high
      intraocular pressures that responded poorly to medical treatment. CONCLUSIONS:
      Two non-synonymous variants, p.Gln297His and p.Ala363Thr, indicate that they are
      involved in the pathogenesis of POAG. p.Ala363Thr has been found in another
      Japanese population and would be useful in genetic testing.

PMID- 18334963
TI  - Glutathione S-transferase M1 and T1 polymorphisms in Arab glaucoma patients.
AB  - PURPOSE: Glutathione S-transferases (GSTs) are a family of enzymes that
      inactivate xenobiotics and endogenous end products formed as secondary
      metabolites during oxidative stress. In humans, GSTT1 and GSTM1 deletion
      genotypes (T0M1, T1M0, and T0M0) are associated with a variety of pathologic
      processes including certain ophthalmologic diseases. METHODS: We compared the
      prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by
      multiplex polymerase chain reaction, in 107 Arab patients with glaucoma (49 with
      primary open-angle glaucoma, 29 with pseudoexfoliation glaucoma, and 29 with
      primary angle-closure glaucoma) to 120 age, sex, and ethnically matched controls.
      RESULTS: All three GST polymorphisms were significantly more common in the entire
      glaucoma group (p<0.0167) than in controls. However, when patients were
      stratified by glaucoma type, the deletion genotype, T0M0, was not particularly
      associated with any type of glaucoma tested. The T1MO genotype was more common
      among patients with each type of glaucoma than among controls whereas T0M1
      genotype was more common among pseudoexfoliation glaucoma (PEG) and primary open
      angle glaucoma (POAG) patients than controls. CONCLUSIONS: The overall results
      indicate a possible variable association between various GSTT1 and GSTM1
      genotypes and glaucoma in this population. Decreased GST function might interfere
      with the metabolism of oxidative intermediates and exacerbate the direct or
      indirect damaging effects of oxidative stress on the optic nerve. It is possible
      that these GST polymorphisms may be risk factors for glaucoma.

PMID- 18334964
TI  - Influence of timing (pre-puberty or skeletal maturity) of ovariohysterectomy on
      mRNA levels in corneal tissues of female rabbits.
AB  - PURPOSE: Corneal thickness and curvature are reported to be influenced by
      hormonal changes associated with menstrual cycle, pregnancy, or menopause.
      However, the molecular mechanisms leading to these alterations are not clearly
      understood. The present study focuses on gene expression patterns (mRNA levels)
      in corneal tissues following surgically induced menopause in an animal model. The
      impact of lower hormone levels on mRNA levels in corneal tissues after pre
      puberty ovariohysterectomy (OVX) was compared to that in skeletally mature adult
      animals. METHODS: Skeletally mature adult female rabbits were either left
      unoperated (control) or were subjected to OVX at 54 weeks of age using an
      approved protocol. The central (approximately 6 mm) and the peripheral corneal
      tissues were harvested from normal and OVX rabbits eight weeks after surgery. In
      a second study, young sexually immature rabbits at eight weeks of age were
      subjected to OVX and corneal tissues were collected when the animals were 22 and
      32 weeks of age. In both experiments, RNA was isolated from corneal tissues and
      RT-PCR was used to assess mRNA levels for several relevant molecules. RESULTS:
      When mature animals were examined eight weeks after OVX, mRNA levels for
      molecules such as the estrogen receptor, decorin, collagen I, collagen V, and
      several growth factors were found to be significantly decreased in central
      corneal tissues. Interestingly, no corresponding changes in mRNA levels were
      observed for these same molecules in peripheral corneal tissues. When young, pre
      pubertal animals were subjected to OVX, mRNA levels were found to be mainly
      unchanged for the OVX animals at 22 weeks of age i.e., after 14 weeks of low
      hormone conditions. However, significant decreases in mRNA levels for a similar
      subset of molecules were observed when the animals were at least 32 weeks of age,
      i.e., after 24 weeks of a low hormone environment. Examination of peripheral
      corneal tissues did not show significant changes in mRNA levels due to OVX at
      either 22 or 32 weeks of age except for collagens I and V at 32 weeks of age.
      CONCLUSIONS: These results indicate significant alterations in mRNA levels in the
      central corneal tissues of rabbits following OVX. Interestingly, peripheral
      corneal tissues show very little alteration in mRNA levels for the same
      molecules. Furthermore, OVX had a more rapid impact on mRNA levels in mature
      animals than in skeletally immature animals. Thus, loss of hormone producing
      tissues during growth and maturation apparently delayed the impact of hormone
      removal compared to loss after maturity had been attained and growth stimuli are
      likely absent. Therefore, specific areas of the cornea are more responsive to
      hormone levels than others. The impact of the loss of hormones is influenced by
      the maturation state of the rabbit, but mRNA levels for a similar subset of genes
      are affected by OVX in both age groups.

PMID- 18334965
TI  - Axonal regeneration after optic nerve crush in Nogo-A/B/C knockout mice.
AB  - PURPOSE: The axonal regeneration of retinal ganglion cells (RGCs) after optic
      nerve (ON) crush was investigated both in vivo and in vitro on Nogo-A/B/C
      knockout mice. METHODS: The study used 20 Nogo-A/B/C knockout mice in the
      experimental group, and 20 C57BL/6 mice in the control group. Partial ON injury
      was induced by using a specially designed ON clip to pinch the ON 1 mm behind the
      mouse eyeball with 40 g pressure for 9 s. The left ON was injured in both groups,
      but the right ON was left untouched in the control group. Nogo-A/B/C mRNA was
      studied by in situ hybridization in both groups. GAP-43 was studied by
      immunofluorescence staining on frozen sections. RGCs were purified and cultured
      in DMEM medium containing B-27. Cells were then immunostained with both Thy1.1
      and GAP-43 antibodies. The axonal growth of RGCs was calculated by a computerized
      image analyzer. RESULTS: GAP-43 expression was significantly higher in the
      experimental group than in the control group (p<0.01). GAP-43 antibody binding
      was demonstrated in the axons of cultured RGCs. Axonal growth was significantly
      more active at every observed time point in the experimental group than in the
      control group (F=43.25, 32.16; p<0.01). CONCLUSIONS: Nogo genes play an
      inhibitive role in the axonal regeneration after ON injury, while Nogo-knockout
      is an effective way to eliminate this inhibition and accelerate axonal
      regeneration.

PMID- 18334966
TI  - A novel connexin 50 (GJA8) mutation in a Chinese family with a dominant
      congenital pulverulent nuclear cataract.
AB  - PURPOSE: To identify the genetic cause responsible for the autosomal dominant
      hereditary cataract in a Chinese family. METHODS: A whole family of a proband who
      has a dominant congenital pulverulent nuclear cataract was recruited into
      Zhongnan Hospital. The lenses of patients were observed by a slit-lamp
      microscope, and the lenses of the proband's mother were analyzed by scanning
      electron microscopy. Mutation screening was performed in the cataract candidate
      genes coding for crystallins and connexin 50 by sequencing of polymerase chain
      reaction (PCR) products amplified from blood leukocyte DNA samples of eight
      family members. The identified mutation was then investigated in other
      participated family members, 200 normal controls, and 40 senile cataract patients
      by the restriction fragment length polymorphism (RFLP) method. RESULTS: The
      structure of the lens opacities of the proband's mother is puffy, and the fibers
      are tangled under a scanning electron microscope. A novel C>T transition at
      nucleotide position 827 was determined in the connexin 50 (GJA8) gene. This
      mutation led to a serine (S) to phenylalanine (F) amino acid substitution in
      amino acid position 276 where the secondary structure prediction suggested a
      helix replaced by a sheet. And the mutation was neither found in the 200 controls
      nor in the 40 senile cataract patients. CONCLUSIONS: A novel GJA8 gene mutation
      was found to be associated with hereditary cataract in a Chinese congenital
      cataract family.

PMID- 18334967
TI  - A role for aquaporin-4 during induction of form deprivation myopia in chick.
AB  - PURPOSE: Aquaporins (AQP) form a family of specialized water channels known to
      transport water across cell membranes and reduce osmotic gradients. The isoform
      AQP4 is highly expressed in the astroglia of the brain and Muller cells in the
      retina. In the brain, AQP4 play a role in the control of cerebral edema by
      shunting excess fluid into blood vessels and by upregulating during conditions of
      hyperosmolarity. Thus, on the basis of the hyperosmolarity seen across the retina
      and choroid of hatchling chickens made myopic by form deprivation (FD), we
      predicted an upregulation of retinal AQP4 expression during induction of myopia.
      METHODS: Two-day-old hatchling chicks were monocularly form-deprived for 48, 72,
      or 96 h, and then after biometric assessment, the eyes of these animals and the
      normal controls of the same age were enucleated. Retinal tissue was prepared
      either for western blot analysis to show the presence of the AQP4 protein in the
      chick retina or for immunolocalization using polyclonal AQP4 antibodies to
      determine regional distribution and intensity of labeling during the induction of
      form deprivation myopia (FDM). RESULTS: As expected, ultrasonography demonstrated
      that all post hatchling eyes showed rapid elongation with occluded eyes
      elongating faster than fellow eyes or normal controls and becoming progressively
      more myopic with the duration of visual deprivation. Western blot analyses
      revealed an approximately 30 kDa band immunoreactive for AQP4 protein and
      confirmed the presence of AQP4 in chicks. Immunohistochemical staining showed the
      greatest positive immunoreactivity for antibodies to AQP4 in the inner retina
      along the vitreoretinal interface, nerve fiber layer, ganglion cell layer, and
      inner plexiform layer in all animals. The control eyes showed relatively constant
      levels of AQP4 expression until day 5 after which the level appeared to decrease.
      By comparison, positive AQP4 immunoreactivity in the nerve fiber layer increased
      significantly over the first 48 h in form-deprived eyes and in fellow eyes and
      then decreased over the next 48 h but not to the level of expression in the
      normal untreated eyes. CONCLUSIONS: This is the first study to demonstrate the
      presence of AQP4 protein in the chick retina and to associate AQP4 expression in
      the inner retina with the initiation of form deprivation and the period of
      fastest axial elongation. This increased expression of AQP4 channels near the
      vitread border during the time of rapid growth suggests a role for AQP4 as a
      conduit for movement of retinal fluid into the vitreous in form-deprived chicks.

PMID- 18334968
TI  - A case of polyomavirus-associated nephropathy presenting late after
      transplantation.
AB  - BACKGROUND: A 36-year-old white female, who had received a deceased-donor kidney
      transplant for end-stage renal disease secondary to reflux nephropathy 8 years
      previously, was referred to a transplant clinic for evaluation following an
      increase in her serum creatinine level from 123.8 micromol/l to 185.6 micromol/l
      (1.4 mg/dl to 2.1 mg/dl) over the preceding 9 months. Her immunosuppression
      regimen included mycophenolate mofetil, ciclosporin and prednisone, with
      ciclosporin trough levels ranging from 100 ng/ml to 150 ng/ml, as detected by
      fluorescence polarization immunoassay, over the preceding year. The following
      possible causes of subacute renal failure were ruled out: post-obstructive
      nephropathy, altered hemodynamics (hypotension and renal artery stenosis), and
      toxicity from medications other than calcineurin inhibitors. Potential etiologies
      such as acute T-cell-mediated rejection, acute and chronic antibody-mediated
      rejection, polyomavirus-associated nephropathy, and calcineurin inhibitor
      nephrotoxicity were considered. INVESTIGATIONS: Physical examination, urine and
      blood analysis, analysis of human leukocyte antigen antibodies by flow cytometry
      (Luminex, Luminex Corporation, Austin, TX), ultrasound of the transplanted
      kidney, polymerase chain reaction assay for the detection of BK virus in the
      serum, and biopsy of the transplanted kidney with staining for simian virus 40
      antigen. DIAGNOSIS: Polyomavirus-associated nephropathy with advanced
      nephrosclerosis and moderate to marked hyaline arteriolosclerosis. MANAGEMENT:
      Reduction of immunosuppression by discontinuation of mycophenolate mofetil, dose
      reduction of ciclosporin, and initiation of leflunomide.

PMID- 18334969
TI  - Adapting the modification of diet in renal disease equation for Japanese
      patients.

PMID- 18334970
TI  - Urinary tract infection in the renal transplant patient.
AB  - Urinary tract infection (UTI) is the most common type of bacterial infection
      contracted by recipients of renal allografts in the post-transplantation period.
      Fungi and viruses can also cause UTIs, but infections caused by these organisms
      are less common than those caused by bacteria. Both the lower and upper urinary
      tract (encompassing grafted or native kidneys) can be affected. Factors that
      might contribute to the development of UTIs include excessive immunosuppression,
      and instrumentation of the urinary tract (e.g. urethral catheters and ureteric
      stents). Antimicrobials are the mainstays of treatment and should be accompanied
      by minimization of immunosuppression when possible. The use of long-term
      antimicrobial prophylaxis is controversial, however, as it might increase the
      likelihood of infective organisms becoming resistant to treatment. There are
      conflicting data on the associations of post-transplantation UTI with graft and
      patient survival.

PMID- 18334971
TI  - Screening history of women with cervical cancer: a 6-year study in Aarhus,
      Denmark.
AB  - To identify possible weaknesses in cervical screening in Aarhus County, 10 years
      after the programme was introduced, screening histories were examined. A major
      problem for the screening programme was that 31% of women were never screened and
      61% under-screened, the latter group being significantly dominated by older women
      and high-stage tumours.

PMID- 18334972
TI  - Activity of lapatinib a novel HER2 and EGFR dual kinase inhibitor in human
      endometrial cancer cells.
AB  - In this study, we explore the therapeutic potential of lapatinib a selective
      inhibitor of both the EGFR and HER2 tyrosine kinases for the treatment of
      endometrial cancer. The effect of lapatinib on tumour cell growth and receptor
      activation was studied in a panel of human endometrial cancer cell lines.
      Candidate molecular markers predicting sensitivity were assessed by baseline gene
      expression profiling, ELISA, and western blot analyses. Multiple drug
      effect/combination index (CI) isobologram analysis was used to study the
      interactions between chemotherapeutic drugs and lapatinib. Concentration
      dependent anti-proliferative effects of lapatinib were seen in all endometrial
      cancer cell lines tested, but varied significantly between individual cell lines
      (IC(50) range: 0.052-10.9 micromol). HER2 overexpression or increased expression
      of EGFR was significantly associated with in vitro sensitivity (P=0.024 or 0.011,
      respectively). Lapatinib exerts growth inhibition in a PTEN-independent manner.
      Sensitive cell lines also exhibited increased expression of EGFR ligands or HER3.
      In contrast, lapatinib-resistant cell lines exhibited high androgen receptor (AR)
      levels or epithelial-to-mesenchymal transition (post-EMT) features. In
      endometrial cancer cells, at a wide range of clinically achievable drug
      concentrations, additive and synergistic interactions were observed for lapatinib
      plus carboplatin, paclitaxel, docetaxel, and doxorubicin. These observations
      provide a clear biologic rational to test lapatinib as a single agent or in
      combination with chemotherapy in endometrial cancer with HER2 overexpression.
      Expression of EGFR, its ligands, HER3, AR, and post-EMT markers warrant further
      evaluation to help define patients with HER2-nonoverexpressing endometrial cancer
      most likely to benefit from lapatinib.

PMID- 18334973
TI  - HLA-associated susceptibility to childhood B-cell precursor ALL: definition and
      role of HLA-DPB1 supertypes.
AB  - Childhood B-cell precursor (BCP) ALL is thought to be caused by a delayed immune
      response to an unidentified postnatal infection. An association between BCP ALL
      and HLA class II (DR, DQ, DP) alleles could provide further clues to the identity
      of the infection, since HLA molecules exhibit allotype-restricted binding of
      infection-derived antigenic peptides. We clustered >30 HLA-DPB1 alleles into six
      predicted peptide-binding supertypes (DP1, 2, 3, 4, 6, and 8), based on amino
      acid di-morphisms at positions 11 (G/L), 69 (E/K), and 84 (G/D) of the DPbeta(1)
      domain. We found that the DPbeta11-69-84 supertype GEG (DP2), was 70% more
      frequent in BCP ALL (n=687; P<10(-4)), and 98% more frequent in cases diagnosed
      between 3 and 6 years (P<10(-4)), but not <3 or >6 years, than in controls. Only
      one of 21 possible DPB1 supergenotypes, GEG/GKG (DP2/DP4) was significantly more
      frequent in BCP ALL (P=0.00004) than controls. These results suggest that
      susceptibility to BCP ALL is associated with the DP2 supertype, which is
      predicted to bind peptides with positively charged, nonpolar aromatic residues at
      the P4 position, and hydrophobic residues at the P1 and P6 positions. Studies of
      peptide binding by DP2 alleles could help to identify infection(s) carrying these
      peptides.

PMID- 18334974
TI  - Is duloxetine safe and effective for the treatment of overactive bladder?

PMID- 18334975
TI  - Is androgen suppression therapy associated with early onset of fatal myocardial
      infarction?

PMID- 18334976
TI  - A case of iliac-artery-ureteral fistula managed with a combined endoscopic
      approach.
AB  - BACKGROUND: A 66-year-old man presented to hospital with gross hematuria and
      clots. He had previously undergone surgical repair of a right iliac artery
      aneurysm with placement of a vascular prosthesis at the same hospital, which had
      resulted in iliac urethral stricture that required the placement of a right
      ureteral stent. He had attended repeatedly for recurrent ureteral stent
      replacement, with the most recent replacement having occurred 1 month before the
      current presentation. INVESTIGATIONS: Ultrasonography, cystography, retrograde
      pyelography and provocative arteriography via a percutaneous right femoral
      arterial approach. DIAGNOSIS: An iliac-artery-ureteral fistula between the right
      ureter and a pseudoaneurysm of the right common iliac artery. MANAGEMENT: The
      patient underwent placement of a covered, self-expandable vascular stent with
      angioplasty balloon, which resulted in complete exclusion of the pseudoaneurysm
      and fistula and resolution of the patient's hematuria. A pigtail catheter was
      placed in the right ureter for 5 days and replaced with a double-J ureteral stent
      on day 6 after exclusion of the pseudoaneurysm; the patient was discharged from
      hospital on the same day. Color-Doppler ultrasonography of the right iliac
      vessels performed 2 months later showed patency of the right iliac artery. The
      patient's ureteral stent has been replaced every 2 months since his discharge
      without recurrence of hematuria.

PMID- 18334977
TI  - Should adults with suspected bacterial meningitis receive adjunctive
      dexamethasone?

PMID- 18334978
TI  - Mechanisms of disease: aquaporin-4 antibodies in neuromyelitis optica.
AB  - Neuromyelitis optica (NMO) is a rare CNS inflammatory disorder that predominantly
      affects the optic nerves and spinal cord. Recent serological findings strongly
      suggest that NMO is a distinct disease rather than a subtype of multiple
      sclerosis. In NMO, serum antibodies, collectively known as NMO-IgG,
      characteristically bind to cerebral microvessels, pia mater and Virchow-Robin
      spaces. The main target antigen for this immunoreactivity has been identified as
      aquaporin-4 (AQP4). The antibodies are highly specific for NMO, and they are also
      found in patients with longitudinally extensive transverse myelitis without optic
      neuritis, which is thought to be a precursor to NMO in some cases. An antibody
      mediated pathogenesis for NMO is supported by several observations, including the
      characteristics of the AQP4 antibodies, the distinct NMO pathology--which
      includes IgG and complement deposition and loss of AQP4 from spinal cord lesions-
      and emerging evidence of the beneficial effects of B-cell depletion and plasma
      exchange. Many aspects of the pathogenesis, however, remain unclear.

PMID- 18334979
TI  - Migraine in adolescents: towards an easy-to-use screening tool.

PMID- 18334980
TI  - Is teriparatide or alendronate the best treatment for glucocorticoid-induced
      osteoporosis?

PMID- 18334981
TI  - Surgery Insight: orthopedic treatment options in rheumatoid arthritis.
AB  - Longstanding rheumatoid arthritis (RA) leads to disability, caused mainly by
      joint destruction. The current goals of surgical intervention are to restore
      function and quality of life, prevent joint deterioration, relieve pain, and
      correct deformity. A number of different surgical treatment options are available
      to patients with RA, including synovectomy, arthrodesis, joint replacement, and
      soft tissue and special hand surgery; nonoperative management is also important.
      Decision-making and timing for orthopedic intervention are complex issues because
      of polyarticular involvement. Functional impairment, pain, and the subsequent
      loss of quality of life and inability to work have become the main considerations
      for surgical reconstruction. Early referral for orthopedic treatment can lead to
      improved functional benefit for patients with RA. The decision for orthopedic
      intervention should be established by an interdisciplinary team that includes
      rheumatologists and orthopedic surgeons experienced in the surgery of RA.
      Priority should be given to the joint that causes the greatest disability and
      pain. Disease progression and pharmaceutical treatment options should be taken
      into consideration when establishing an orthopedic intervention protocol.

PMID- 18334982
TI  - Canadian recommendations for the management of spondyloarthritis address many
      different levels of patient care.

PMID- 18334983
TI  - Thymol and related alkyl phenols activate the hTRPA1 channel.
AB  - BACKGROUND AND PURPOSE: Thymol, a major component of thyme and oregano, has
      medical uses in oral care products as an astringent and antibiotic. Its
      distinctive sharp odour and pungent flavour are considered aversive properties.
      The molecular basis of these aversive properties is not well understood.
      EXPERIMENTAL APPROACH: The ability of thymol to activate human transient receptor
      potential channel A1 (hTRPA1) expressed in stably transfected human embryonic
      kidney 293 (HEK293) cells was measured by membrane potential and calcium
      sensitive dyes in a fluorescence-imaging plate reader (FLIPR) assay. Direct
      activation of hTRPA1 currents was measured by whole-cell voltage clamp recording.
      Intracellular calcium changes were measured using fura-2 dye. The FLIPR assay was
      also used to measure membrane potential changes elicited by thymol after
      pretreatment with camphor, a known TRPA1 inhibitor. The ability of related alkyl
      phenols to activate hTRPA1 was also determined. KEY RESULTS: Thymol potently
      activated a membrane potential response and intracellular calcium increase in
      hTRPA1-expressing HEK293 cells in a concentration-dependent manner. Activation by
      thymol desensitized hTRPA1 to further exposure to thymol or the known ligand
      allyl isothiocyanate (AITC). The related phenols 2-tert-butyl-5-methylphenol, 2,6
      diisopropylphenol (propofol) and carvacrol also activated hTRPA1. Phenols with
      less bulky carbon substitutions and lower logP values were less potent in
      general. The response to thymol was blocked by camphor. CONCLUSIONS AND
      IMPLICATIONS: These results suggest a role for hTRPA1 activation in the reported
      pungent and aversive properties of some of these pharmaceutically important
      phenols.

PMID- 18334984
TI  - Gene therapy of beta(c)-deficient pulmonary alveolar proteinosis (beta(c)-PAP):
      studies in a murine in vivo model.
AB  - Pulmonary alveolar proteinosis (PAP) due to deficiency of the common beta-chain
      (beta(c)) of the interleukin-3 (IL-3)/IL-5/granulocyte-macrophage colony
      stimulating factor (GM-CSF) receptors is a rare monogeneic disease characterized
      by functional insufficiency of pulmonary macrophages. Hematopoietic stem cell
      gene therapy for restoring expression of beta(c)-protein in the hematopoietic
      system may offer a curative approach. Toward this end, we generated a retroviral
      construct expressing the murine beta(c) (mbeta(c)) gene and conducted
      investigations in a murine model of beta(c)-deficient PAP. Functional correction
      of mbeta(c) activity in mbeta(c)(-/-) bone marrow (BM) cells was demonstrated by
      restoration of in vitro colony formation in response to GM-CSF. In addition, in a
      murine in vivo model of mbeta(c)-deficient PAP mbeta(c) gene transfer to
      hematopoietic stem cells not only restored the GM-CSF-sensitivity of
      hematopoietic progenitor cells but also, within a period of 12 weeks, almost
      completely reversed the morphologic features of surfactant accumulation. These
      results were obtained despite modest transduction levels (10-20%) and, in
      comparison to wild-type mice, clearly reduced beta(c) expression levels were
      detected in hematopoietic cells. Therefore, our data demonstrating genetic and
      functional correction of mbeta(c)(-/-) deficiency in vitro as well as in a murine
      in vivo model of PAP strongly suggest gene therapy as a potential new treatment
      modality in beta(c)-deficient PAP.

PMID- 18334985
TI  - Physiological promoters reduce the genotoxic risk of integrating gene vectors.
AB  - The possible activation of cellular proto-oncogenes as a result of clonal
      transformation is a potential limitation in a therapeutic approach involving
      random integration of gene vectors. Given that enhancer promiscuity represents an
      important mechanism of insertional transformation, we assessed the enhancer
      activities of various cellular and retroviral promoters in transient transfection
      assays, and also in a novel experimental system designed to measure the
      activation of a minigene cassette contained in stably integrating retroviral
      vectors. Retroviral enhancer-promoters showed a significantly greater potential
      to activate neighboring promoters than did cellular promoters derived from human
      genes, elongation factor-1alpha (EF1alpha) and phosphoglycerate kinase (PGK).
      Self-inactivating (SIN) vector design reduced but did not abolish enhancer
      interactions. Using a recently established cell culture assay that detects
      insertional transformation by serial replating of primary hematopoietic cells, we
      found that SIN vectors containing the EF1alpha promoter greatly decrease the risk
      of insertional transformation. Despite integration of multiple copies per cell,
      activation of the crucial proto-oncogene Evi1 was not detectable when using SIN
      EF1alpha vectors. On the basis of several quantitative indicators, the decrease
      in transforming activity was highly significant (more than tenfold, P < 0.01)
      when compared with similarly designed vectors containing a retroviral enhancer
      promoter with or without a well-characterized genetic insulator core element. In
      this manner, the insertional biosafety of therapeutic gene vectors can be greatly
      enhanced and proactively evaluated in sensitive cell-based assays.

PMID- 18334986
TI  - Systemic microdystrophin gene delivery improves skeletal muscle structure and
      function in old dystrophic mdx mice.
AB  - Restoring dystrophin expression in the muscles of patients with Duchenne muscular
      dystrophy (DMD) may halt or reverse the degenerative wasting and weakness that
      causes premature death. However, the therapeutic efficacy of an intervention may
      be limited by the extent of disease progression prior to treatment. In this
      study, we considered the potential for ameliorating the pathology in a mouse
      model of advanced-stage muscular dystrophy by systemic administration of
      recombinant adeno-associated viral (rAAV6) vectors encoding a microdystrophin
      expression construct. The treatment of 20-month-old mdx mice restored body-wide
      expression of a dystrophin-based protein in striated musculature. In aged mice
      that received treatment, the resultant dystrophin expression was associated with
      improved hindlimb and respiratory muscle morphology and function, concomitant
      with reduced muscle fiber degeneration. The findings demonstrate that an
      established dystrophic state remains amenable to improvement with appropriate
      intervention and, by some measures, may even achieve benefits similar to those
      observed with intervention early in disease progression. The capacity to
      ameliorate the pathology in an animal model of advanced-stage muscular dystrophy
      suggests that interventions ultimately proven to exert a therapeutic effect in
      young patients may offer benefits to older patients or those with advanced
      conditions of progressive muscular dystrophy.

PMID- 18334987
TI  - Transduction of full-length dystrophin to multiple skeletal muscles improves
      motor performance and life span in utrophin/dystrophin double knockout mice.
AB  - Duchenne muscular dystrophy (DMD) is a fatal, progressive, muscle-wasting disease
      caused by defects in the dystrophin. No viral vector except the helper-dependent
      adenovirus vector (HDAdv) can package 14-kilobase (kb) full-length dystrophin
      complementary DNA (cDNA), and HDAdv is considerably safer than old-generation
      adenovirus vectors because of the large-size deletion in its genome. We have
      generated HDAdv that carries myc-tagged murine full-length dystrophin cDNA (HDAdv
      myc-mFLdys). We injected it into multiple proximal muscles of 7-day-old
      utrophin/dystrophin double knockout mice (dko mice) (which typically show
      symptoms quite similar to human DMD) because the proximal muscles are affected in
      DMD patients. Eight weeks after the injections, the transduced dystrophin was
      widely expressed, and we found a significant reduction in centrally nucleated
      myofibers and the restoration of the dystrophin-associated proteins, beta
      dystroglycan (beta-DG) and alpha-sarcoglycan (alpha-SG), as well as neuronal
      nitric oxide synthase (nNOS). The injected dko mice also showed an increase in
      body weight, an improvement in motor performance, and a prolongation of life
      span. Using HDAdv, we could treat DMD model mice even by transferring the
      therapeutic gene into multiple skeletal muscles. Our results suggest that
      multiple intramuscular administrations of HDAdv carrying full-length dystrophin
      cDNA may reduce symptoms and compensate for lost functions in DMD patients.

PMID- 18334988
TI  - Comparison of zinc finger nucleases for use in gene targeting in mammalian cells.
AB  - Homologous recombination is a technique used for performing precise genomic
      manipulations, and this makes it potentially ideal for gene therapy. The rate of
      spontaneous homologous recombination in human cells has been too low to be used
      experimentally or therapeutically but, by inducing a DNA double-strand break
      (DSB) in the target gene this rate can be stimulated. Zinc finger nucleases
      (ZFNs) are synthetic fusion proteins that can induce DSBs at specific sequences
      of DNA and stimulate gene targeting. Although the success of ZFNs in this
      application has been demonstrated, several issues remain. First, an optimal,
      generalized method of making effective and safe ZFNs needs to be determined.
      Second, a systematic method of evaluating the efficiency and safety of ZFNs is
      needed. We compared the gene-targeting efficiencies and cytotoxicity of ZFNs made
      using modular-assembly and ZFNs made using a bacterial 2-hybrid (B2H) selection
      based method, in each case targeting the same single site. We found that a ZFN
      pair made using the B2H strategy is more efficient at stimulating gene targeting
      and less toxic than a pair made using modular-assembly. We demonstrate that a
      pair of three-finger B2H ZFNs is as efficient at stimulating gene targeting as
      ZFNs with more fingers, and induce similar or lower rates of toxicity.

PMID- 18334989
TI  - Genetic complementation of human muscle cells via directed stem cell fusion.
AB  - Duchenne muscular dystrophy (DMD) is caused by mutations in the X chromosome
      linked DMD gene, which encodes the sarcolemma-stabilizing protein-dystrophin.
      Initial attempts at DMD therapy deployed muscle progenitor cells from healthy
      donors. The utilization of these cells is, however, hampered by their
      immunogenicity, while those from DMD patients are scarce and display limited ex
      vivo replication. Nonmuscle cells with myogenic capacity may offer valuable
      alternatives especially if, to allow autologous transplantation, they are
      amenable to genetic intervention. As a paradigm for therapeutic gene transfer by
      heterotypic cell fusion we are investigating whether human mesenchymal stem cells
      (hMSCs) can serve as donors of recombinant DMD genes for recipient human muscle
      cells. Here, we show that forced MyoD expression in hMSCs greatly increases their
      tendency to participate in human myotube formation turning them into improved DNA
      delivery vehicles. Efficient loading of hMSCs with recombinant DMD was achieved
      through a new tropism-modified high-capacity adenoviral (hcAd) vector directing
      striated muscle-specific synthesis of full-length dystrophin. This study
      introduces the principle of genetic complementation of gene-defective cells via
      directed cell fusion and provides an initial framework to test whether transient
      MyoD synthesis in autologous, gene-corrected hMSCs increases their potential for
      treating DMD and, possibly, other muscular dystrophies.

PMID- 18334990
TI  - A comprehensive platform for ex vivo T-cell expansion based on biodegradable
      polymeric artificial antigen-presenting cells.
AB  - Efficient T-cell stimulation and proliferation in response to specific antigens
      is a goal of immunotherapy against infectious disease and cancer. Manipulation of
      this response can be accomplished by adoptive immunotherapy involving the
      infusion of antigen-specific T-cell populations expanded ex vivo with antigen
      presenting cells. We mimicked physiological antigen presentation on a
      biodegradable microparticle constructed from poly(lactide-co-glycolide) (PLGA), a
      polymer system whose safety has been established for use in humans. These
      particles present a high density of adaptor elements for attaching both
      recognition ligands and co-stimulatory ligands to a biodegradable core
      encapsulating the cytokine interleukin-2 (IL-2). We demonstrate the utility of
      this system in efficient polyclonal and antigen-specific T-cell stimulation and
      expansion, showing that sustained release of IL-2 in the vicinity of T-cell
      contacts dramatically improves the stimulatory capacity of these acellular
      systems, as compared to the effect of exogenous addition of cytokine. This
      results in a 45-fold enhancement in T-cell expansion. In addition, this mode of
      antigen presentation skews the expansion toward the CD8(+) T-cell phenotype. This
      comprehensive acellular platform, capable of delivering recognition, co
      stimulatory, and cytokine signals, represents a promising new technology for
      artificial antigen presentation.

PMID- 18334991
TI  - The role of allografting in adults with acute leukaemia.

PMID- 18334992
TI  - Allogeneic transplantation for ALL in adults.
AB  - Allogeneic transplantation is an effective treatment for adult patients with high
      risk ALL, including patients in first or second remission. Although only a few
      studies have evaluated the optimal transplant regimens, the data would suggest
      that a TBI-based regimen results in better disease control. Although not as
      potent as it is in other hematologic malignancies, the GVL effect is an important
      component of achieving cure of ALL. Because of the toxicity of the fully ablative
      regimen, reduced-intensity transplants are being explored in older patients with
      ALL when the prognosis is especially poor with standard chemotherapy.

PMID- 18334993
TI  - Brief exposure to hyperoxia depletes the glial progenitor pool and impairs
      functional recovery after hypoxic-ischemic brain injury.
AB  - Patterns of hypoxic-ischemic brain injury in infants and children suggest
      vulnerability in regions of white matter development, and injured patients
      develop defects in myelination resulting in cerebral palsy and motor deficits.
      Reperfusion exacerbates the oxidative stress that occurs after such injuries and
      may impair recovery. Resuscitation after hypoxic-ischemic injury is routinely
      performed using 100% oxygen, and this practice may increase the oxidative stress
      that occurs during reperfusion and further damage an already compromised brain.
      We show that brief exposure (30 mins) to 100% oxygen during reperfusion worsens
      the histologic injury in young mice after unilateral brain hypoxia-ischemia,
      causes an accumulation of the oxidative metabolite nitrotyrosine, and depletes
      preoligodendrocyte glial progenitors present in the cortex. This damage can be
      reversed with administration of the antioxidant ebselen, a glutathione peroxidase
      mimetic. Moreover, mice recovered in 100% oxygen have a more disrupted pattern of
      myelination and develop a static motor deficit that mimics cerebral palsy and
      manifests itself by significantly worse performance on wire hang and rotorod
      motor testing. We conclude that exposure to 100% oxygen during reperfusion after
      hypoxic-ischemic brain injury increases secondary neural injury, depletes
      developing glial progenitors, interferes with myelination, and ultimately impairs
      functional recovery.

PMID- 18334994
TI  - Toward safer thrombolytic agents in stroke: molecular requirements for NMDA
      receptor-mediated neurotoxicity.
AB  - Current thrombolytic therapy for acute ischemic stroke with tissue-type
      plasminogen activator (tPA) has clear global benefits. Nevertheless, evidences
      argue that in addition to its prohemorrhagic effect, tPA might enhance
      excitotoxic necrosis. In the brain parenchyma, tPA, by binding to and then
      cleaving the amino-terminal domain (ATD) of the NR1 subunit of N-methyl-D
      aspartate (NMDA) glutamate receptors, increases calcium influx to toxic levels.
      We show here that tPA binds the ATD of the NR1 subunit by a two-sites system
      (K(D)=24 nmol/L). Although tenecteplase (TNK) and reteplase also display two
      sites binding profiles, the catalytically inactive mutant TNKS478A displays a one
      site binding profile and desmoteplase (DSPA), a kringle 2 (K2) domain-free
      plasminogen activator derived from vampire bat, does not interact with NR1.
      Moreover, we show that in contrast to tPA, DSPA does not promote excitotoxicity.
      These findings, together with three-dimensional (3D) modeling, show that a
      critical step for interaction of tPA with NR1 is the binding of its K2 domain,
      followed by the binding of its catalytic domain, which in turn cleaves the NR1
      subunit at its ATD, leading to a subsequent potentiation of NMDA-induced calcium
      influx and neurotoxicity. This could help design safer new generation
      thrombolytic agents for stroke treatment.

PMID- 18334997
TI  - Multifunctional deadenylase complexes diversify mRNA control.
AB  - Dynamic changes of the lengths of mRNA poly(A) tails are catalysed by diverse
      deadenylase enzymes. Modulating the length of the poly(A) tail of an mRNA is a
      widespread means of controlling protein production and mRNA stability. Recent
      insights illuminate the specialized activities, biological functions and
      regulation of deadenylases. We propose that the recruitment of multifunctional
      deadenylase complexes provides unique opportunities to control mRNAs and that the
      heterogeneity of the deadenylase complexes is exploited to control translation
      and mRNA stability.

PMID- 18334999
TI  - Effects of development and enculturation on number representation in the brain.
AB  - A striking way in which humans differ from non-human primates is in their ability
      to represent numerical quantity using abstract symbols and to use these 'mental
      tools' to perform skills such as exact calculations. How do functional brain
      circuits for the symbolic representation of numerical magnitude emerge? Do neural
      representations of numerical magnitude change as a function of development and
      the learning of mental arithmetic? Current theories suggest that cultural number
      symbols acquire their meaning by being mapped onto non-symbolic representations
      of numerical magnitude. This Review provides an evaluation of this contention and
      proposes hypotheses to guide investigations into the neural mechanisms that
      constrain the acquisition of cultural representations of numerical magnitude.

PMID- 18334998
TI  - Intake of household salt in a Danish population.
AB  - OBJECTIVE: To quantify the intake of household salt and its contribution to the
      total salt intake in a Danish population. METHODS: Eighty-seven healthy
      individuals (37 men and 50 women), aged 20-55 years, recruited from the area of
      Copenhagen, completed the study. Total salt intake was estimated from the mean
      urinary excretion of sodium in four 24-h collections. Household salt, added to
      the food by the volunteers, was assessed using a lithium-marker technique.
      RESULTS: Total salt intake was 10.6+/-3.3 g day(-1) (mean+/-s.d.) in men and
      7.1+/-2.3 g day(-1) in women. Median intake of household salt was 1.0 g day(-1)
      in men and 0.5 g day(-1) in women, corresponding to 10.2 and 8.7% of total salt
      intake in men and women, respectively. A significant difference between sexes was
      found regarding total salt intake (P<0.0001), but no difference was found if
      total salt intake was measured per energy intake. No significant difference was
      found between sexes regarding intake of household salt, and neither the
      educational level nor the age was associated to either total salt intake or
      intake of household salt. CONCLUSION: These findings support the assertion that
      the total salt intake in the Danish population is above the recommended intake
      and that the salt intake cannot be sufficiently lowered simply by lowering the
      use of household salt. Focus needs to be addressed to salt added during the
      processing or manufacture of foods, as this is the greatest source of salt intake
      at least in this group of healthy volunteers.

PMID- 18335000
TI  - Mesenchymal stem cells for graft-versus-host disease: a double edged sword?

PMID- 18335002
TI  - Predictors of personal air concentrations of chloroform among US adults in NHANES
      1999-2000.
AB  - Volunteer studies suggest that showering/bathing with chlorinated tap water
      contributes to daily chloroform inhalation exposure for the majority of US
      adults. We used data from the 1999-2000 US National Health and Nutrition
      Examination Survey (NHANES) and weighted multiple linear regression to test the
      hypothesis that personal exposure microevents such as showering or spending time
      at a swimming pool would be significantly associated with chloroform levels in 2
      3 day personal air samples. The NHANES data show that eight of 10 US adults are
      exposed to detectable levels of chloroform. Median (1.13 microg/m(3)), upper
      percentile (95th, 12.05 microg/m(3)), and cancer risk estimates were similar to
      those from recent US regional studies. Significant predictors of log personal air
      chloroform in our model (R(2)=0.34) included age, chloroform concentrations in
      home tap water, having no windows open at home during the sampling period,
      visiting a swimming pool during the sampling period, living in a mobile
      home/trailer or apartment versus living in a single family (detached) home, and
      being Non-Hispanic Black versus Non-Hispanic White, although the race/ethnicity
      estimates appear influenced by several outlying observations. Reported showering
      activity was not a significant predictor of personal air chloroform, possibly due
      to the wording of the NHANES shower question. The NHANES measurements likely
      underestimate true inhalation exposures since subjects did not wear sampling
      badges while showering or swimming, and because of potential undersampling by the
      passive monitors. Research is needed to quantify the potential difference.

PMID- 18335003
TI  - Assessing exposure to allied ground troops in the Vietnam War: a comparison of
      AgDRIFT and Exposure Opportunity Index models.
AB  - The AgDRIFT aerial dispersion model is well validated and closely related to the
      AGDISP model developed by the USDA Forest Service to determine on- and off-target
      deposition and penetration of aerially applied pesticide through foliage of
      trees. The Exposure Opportunity Index (EOI) model was developed to estimate
      relative exposure of ground troops in Vietnam to aerially applied herbicides. We
      compared the output of the two models to determine whether their predictions were
      in substantial agreement, but found a total lack of concordance. While the
      AgDRIFT model estimated that ground-level deposition through foliage was reduced
      more than 20 orders of magnitude at less than 1 km from the flight line, the EOI
      model predicted deposition declines less than one order of magnitude 4 km from
      the flight line. Interestingly the EOI model predicts a four-fold variability in
      EOI on the flight line, where exposure should be essentially invariant because
      the spray apparatus is designed to apply herbicide at a constant rate. We believe
      that the EOI model cannot be used to provide individual exposure estimates for
      the purpose of conducting epidemiologic studies. Moreover, evaluation of the
      position data for both herbicide spray swaths and troop locations, together with
      the actual patterns of spray deposition predicted by the AgDRIFT model, suggests
      that precise individual-level exposure assessments for ground troops in Vietnam
      are impossible. However, we suggest that well-validated tools like AgDRIFT can be
      used to estimate exposure to groups of individuals.

PMID- 18335004
TI  - An in vitro method to study the effects of hematopoietic regulators during immune
      and blood cell development.
AB  - In adults, hematopoiesis occurs in bone marrow (BM) through a complex process
      with differentiation of hematopoietic stem cells (HSCs) to immune and blood
      cells. Human HSCs and their progenitors express CD34. Methods on hematopoietic
      regulation are presented to show the effects of the chemokine, stromal-derived
      growth factor (SDF)-1I and the neuropeptide, substance P (SP). SDF-1I production
      in BM stroma causes interactions with HSCs, thereby retaining the HSCs in regions
      close to the endosteum, at low oxygen. Small changes in SDF-1I levels stimulate
      HSC functions through direct and indirect mechanisms. The indirect method occurs
      by SP production, which stimulates CD34+ cells, supported by ligand-binding
      studies, long-term culture-initiating cell assays for HSC functions, and
      clonogenic assays for myeloid progenitors. These methods can be applied to study
      other hematopoietic regulators.

PMID- 18335005
TI  - Possible Biomechanical Origins of the Long-Range Correlations in Stride Intervals
      of Walking.
AB  - When humans walk, the time duration of each stride varies from one stride to the
      next. These temporal fluctuations exhibit long-range correlations. It has been
      suggested that these correlations stem from higher nervous system centers in the
      brain that control gait cycle timing. Existing proposed models of this phenomenon
      have focused on neurophysiological mechanisms that might give rise to these long
      range correlations, and generally ignored potential alternative mechanical
      explanations. We hypothesized that a simple mechanical system could also generate
      similar long-range correlations in stride times. We modified a very simple
      passive dynamic model of bipedal walking to incorporate forward propulsion
      through an impulsive force applied to the trailing leg at each push-off. Push-off
      forces were varied from step to step by incorporating both "sensory" and "motor"
      noise terms that were regulated by a simple proportional feedback controller. We
      generated 400 simulations of walking, with different combinations of sensory
      noise, motor noise, and feedback gain. The stride time data from each simulation
      were analyzed using detrended fluctuation analysis to compute a scaling exponent,
      a. This exponent quantified how each stride interval was correlated with previous
      and subsequent stride intervals over different time scales. For different
      variations of the noise terms and feedback gain, we obtained short-range
      correlations (alpha < 0.5), uncorrelated time series (alpha = 0.5), long-range
      correlations (0.5 < alpha < 1.0), or Brownian motion (alpha > 1.0). Our results
      indicate that a simple biomechanical model of walking can generate long-range
      correlations and thus perhaps these correlations are not a complex result of
      higher level neuronal control, as has been previously suggested.

PMID- 18335007
TI  - The 6-plus-person lift transfer technique compared with other methods of spine
      boarding.
AB  - CONTEXT: To achieve full spinal immobilization during on-the-field management of
      an actual or potential spinal injury, rescuers transfer and secure patients to a
      long spine board. Several techniques can be used to facilitate this patient
      transfer. OBJECTIVE: To compare spinal segment motion of cadavers during the
      execution of the 6-plus-person (6+) lift, lift-and-slide (LS), and logroll (LR)
      spine-board transfer techniques. DESIGN: Crossover study. SETTING: Laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Eight medical professionals (1 woman, 7 men) with
      5 to 32 years of experience were enlisted to help carry out the transfer
      techniques. In addition, test conditions were performed on 5 fresh cadavers (3
      males, 2 females) with a mean age of 86.2 +/- 11.4 years. MAIN OUTCOMES
      MEASURE(S): Three-dimensional angular and linear motions initially were recorded
      during execution of transfer techniques, initially using cadavers with intact
      spines and then after C5-C6 spinal segment destabilization. The mean maximal
      linear displacement and angular motion obtained and calculated from the 3 trials
      for each test condition were included in the statistical analysis. RESULTS:
      Flexion-extension angular motion, as well as anteroposterior and distraction
      compression linear motion, did not vary between the LR and either the 6+ lift or
      LS. Compared with the execution of the 6+ lift and LS, the execution of the LR
      generated significantly more axial rotation (P = .008 and .001, respectively),
      more lateral flexion (P = .005 and .003, respectively), and more medial-lateral
      translation (P = .003 and .004, respectively). CONCLUSIONS: A small amount of
      spinal motion is inevitable when executing spine-board transfer techniques;
      however, the execution of the 6+ lift or LS appears to minimize the extent of
      motion generated across a globally unstable spinal segment.

PMID- 18335008
TI  - The combined tool approach for face mask removal during on-field conditions.
AB  - CONTEXT: An effective approach to emergency removal of the face mask (FM) from a
      football helmet should include successful removal of the FM and limitation of
      both the time required and the movement created during the process. Current
      recommendations and practice are to use a cutting tool to remove the FM.
      Researchers recently have suggested an alternate approach that combines the use
      of a cordless screwdriver and a cutting tool. This combined tool approach has not
      been studied, and FM removal has not been studied in a practical setting.
      OBJECTIVE: To investigate the effectiveness and speed of using a combined tool
      approach to remove the FMs from football helmets during on-field conditions
      throughout the course of a football season. DESIGN: Randomized multigroup design.
      SETTING: Practice field of 1 National Collegiate Athletic Association Division II
      football college. PATIENTS OR OTHER PARTICIPANTS: Eighty-four members of 1
      football team. INTERVENTION(S): We used a battery-operated screwdriver for FM
      removal and resorted to using a cutting tool as needed. MAIN OUTCOME MEASURE(S):
      We tracked FM removal success and failure and trial time and compared results
      based on helmet characteristics, weather variables, and the seasonal timing of
      the removal trial. RESULTS: Of the 84 players, 76 were available for data
      collection trials. Overall, 98.6% (75/76) of FM removal trials were successful
      and resulted in a mean removal time of 40.09 +/- 15.1 seconds. We found no
      differences in FM removal time throughout the course of the season. No
      differences in effectiveness or trial time were found among helmet
      characteristics, weather variables, or the timing of the trial. CONCLUSIONS:
      Combining the cordless screwdriver and cutting tool provided a fast and reliable
      means of on-field FM removal in this Division II setting. Despite the excellent
      overall result, 1 FM was not removed in a timely manner. Therefore, we recommend
      that athletic trainers practice helmet removal to be prepared should FM removal
      fail.

PMID- 18335009
TI  - Patellar taping, patellofemoral pain syndrome, lower extremity kinematics, and
      dynamic postural control.
AB  - CONTEXT: Patellar taping has been a part of intervention for treatment of
      patellofemoral pain syndrome (PFPS). However, research on the efficacy of
      patellar taping on lower extremity kinematics and dynamic postural control is
      limited. OBJECTIVE: To evaluate the effects of patellar taping on sagittal-plane
      hip and knee kinematics, reach distance, and perceived pain level during the Star
      Excursion Balance Test (SEBT) in individuals with and without PFPS. DESIGN:
      Repeated-measures design with 2 within-subjects factors and 1 between-subjects
      factor. SETTING: The University of Toledo Athletic Training Research Laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Twenty participants with PFPS and 20 healthy
      participants between the ages of 18 and 29 years. INTERVENTION(S): The
      participants performed 3 reaches of the SEBT in the anterior direction under tape
      and no-tape conditions on both legs. MAIN OUTCOME MEASURE(S): The participants'
      hip and knee sagittal-plane kinematics were measured using the electromagnetic
      tracking system. Reach distance was recorded by hand and was normalized by
      dividing the distance by the participants' leg length (%MAXD). After each taping
      condition on each leg, the participants rated the perceived pain level using the
      10-cm visual analog scale. RESULTS: The participants with PFPS had a reduction in
      pain level with patellar tape application compared with the no-tape condition (P
      = .005). Additionally, participants with PFPS demonstrated increased %MAXD under
      the tape condition compared with the no-tape condition, whereas the healthy
      participants demonstrated decreased %MAXD with tape versus no tape (P = .028). No
      statistically significant differences were noted in hip flexion and knee flexion
      angles. CONCLUSIONS: Although patellar taping seemed to reduce pain and improve
      SEBT performance of participants with PFPS, the exact mechanisms of these
      phenomena cannot be explained in this study. Further research is warranted to
      investigate the effect of patellar taping on neuromuscular control during dynamic
      postural control.

PMID- 18335010
TI  - Muscle stiffness and spinal stretch reflex sensitivity in the triceps surae.
AB  - CONTEXT: Greater musculotendinous stiffness may enhance spinal stretch reflex
      sensitivity by improving mechanical coupling of the muscle spindle and the
      stretch stimulus. This heightened sensitivity would correspond with a shorter
      latency and higher-amplitude reflex response, potentially enhancing joint
      stability. OBJECTIVE: To compare spinal stretch reflex latency and amplitude
      across groups that differed in musculotendinous stiffness. DESIGN: Static group
      comparisons. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Forty
      physically active individuals (20 men, 20 women). INTERVENTION(S): We verified a
      sex difference in musculotendinous stiffness and compared spinal stretch reflex
      latency and amplitude in high-stiffness (men) and low-stiffness (women) groups.
      We also evaluated relationships between musculotendinous stiffness and spinal
      stretch reflex latency and amplitude, respectively. MAIN OUTCOME MEASURE(S):
      Triceps surae musculotendinous stiffness and soleus spinal stretch reflex latency
      and amplitude were assessed at 30% of a maximal voluntary isometric plantar
      flexion contraction. RESULTS: The high-stiffness group demonstrated significantly
      greater stiffness (137.41 +/- 26.99 N/cm) than the low-stiffness group did (91.06
      +/- 20.10 N/cm). However, reflex latency (high stiffness = 50.11 +/- 2.07
      milliseconds, low stiffness = 48.26 +/- 2.40 milliseconds) and amplitude (high
      stiffness = 0.28% +/- 0.12% maximum motor response, low stiffness = 0.31% +/-
      0.16% maximum motor response) did not differ significantly across stiffness
      groups. Neither reflex latency (r = .053, P = .746) nor amplitude (r = .073, P =
      .653) was related significantly to musculotendinous stiffness. CONCLUSIONS: A
      moderate level of pretension (eg, 30%) likely eliminates series elastic slack;
      thus, a greater change in force per unit-of-length change (ie, heightened
      stiffness) would have minimal effects on coupling of the muscle spindle and the
      stretch stimulus and, therefore, on spinal stretch reflex sensitivity. It appears
      unlikely that differences in musculotendinous stiffness influenced spinal stretch
      reflex sensitivity when initiated from a moderate level of pretension.
      Consequently, differences in musculotendinous stiffness did not appear to
      influence dynamic joint stability with respect to reflexive neuromuscular
      control.

PMID- 18335011
TI  - Ankle bracing, plantar-flexion angle, and ankle muscle latencies during inversion
      stress in healthy participants.
AB  - CONTEXT: Ankle braces may enhance ankle joint proprioception, which in turn may
      affect reflexive ankle muscle activity during a perturbation. Despite the common
      occurrence of plantar-flexion inversion ankle injuries, authors of previous
      studies of ankle muscle latencies have focused on inversion stresses only.
      OBJECTIVE: To examine the latency of the peroneus longus (PL), peroneus brevis
      (PB), and tibialis anterior (TA) muscles in response to various degrees of
      combined plantar-flexion and inversion stresses in braced and unbraced
      asymptomatic ankles. DESIGN: Repeated measures. SETTING: University biomechanics
      laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty-eight healthy females and 12
      healthy males (n = 40: mean age = 23.63 years, range = 19 to 30 years; height =
      172.75 +/- 7.96 cm; mass = 65.53 +/- 12.0 kg). INTERVENTION(S): Participants were
      tested under 2 conditions: wearing and not wearing an Active Ankle T1 brace while
      dropping from a custom-made platform into 10 degrees , 20 degrees , and 30
      degrees of plantar flexion and 30 degrees of inversion. MAIN OUTCOME MEASURE(S):
      The time between platform drop and the onset of PL, PB, and TA electromyographic
      activity was measured to determine latencies. We calculated a series of 2-way
      analyses of variance to determine if latencies were different between the
      conditions (braced and unbraced) and among the plantar-flexion angles (alpha =
      .05). RESULTS: No interaction was found between condition and plantar-flexion
      angle. No significant main effects were found for condition or plantar-flexion
      angle. Overall means for braced and unbraced conditions were not significantly
      different for each muscle tested. Overall means for angle for the PL, PB, and TA
      were not significantly different. CONCLUSIONS: Reflexive activity of the PL, PB,
      or TA was unaffected by the amount of plantar flexion or by wearing an Active
      Ankle T1 brace during an unanticipated plantar-flexion inversion perturbation.

PMID- 18335012
TI  - Assessment tools for identifying functional limitations associated with
      functional ankle instability.
AB  - CONTEXT: Assessment tools should identify functional limitations associated with
      functional ankle instability (FAI) by discriminating unstable from stable ankles.
      OBJECTIVE: To identify assessment tools that discriminated FAI from stable ankles
      and determine the most accurate assessment tool for discriminating between FAI
      and stable ankles. DESIGN: Case-control study. SETTING: Research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Fifteen individuals with FAI and 15 healthy
      individuals; participants with unilateral FAI reported "giving-way" sensations
      and ankle sprains, whereas healthy participants did not. INTERVENTION(S):
      Participants answered 12 questions on the Ankle Joint Functional Assessment Tool
      (AJFAT). They also performed a single-leg jump landing, which required them to
      jump to half their maximum jump height, land on a single leg, and stabilize
      quickly on a force plate. MAIN OUTCOME MEASURE(S): Receiver operating
      characteristic curves determined cutoff scores for discriminating between ankle
      groups for AJFAT total score and resultant vector (RV) time to stabilization.
      Accuracy values for discriminating between groups were determined by calculating
      the area under the receiver operating characteristic curves. RESULTS: The cutoff
      score for discriminating between FAI and stable ankles was > or =26 (sensitivity
      = 1, specificity = 1) and > or =1.58 seconds (sensitivity = 0.67, specificity =
      0.73) for the AJFAT total score and RV time to stabilization, respectively. The
      area under the curve for the AJFAT was 1.0 (asymptotic significance <.05),
      whereas the RV time to stabilization had an area under the curve of 0.72
      (asymptotic significance <.05). CONCLUSIONS: The AJFAT was an excellent
      assessment tool for discriminating between ankle groups, whereas RV time to
      stabilization was a fair assessment tool. Although both assessments discriminated
      between ankle groups, the AJFAT more accurately discriminated between groups than
      the RV time to stabilization did. Future researchers should confirm these
      findings using a prospective research design.

PMID- 18335013
TI  - Eccentric plantar-flexor torque deficits in participants with functional ankle
      instability.
AB  - CONTEXT: Inversion ankle sprains can lead to a chronic condition called
      functional ankle instability (FAI). Limited research has been reported regarding
      isokinetic measures for the plantar flexors and dorsiflexors of the ankle.
      OBJECTIVE: To examine the isokinetic eccentric torque measures of the ankle
      musculature in participants with stable ankles and participants with functionally
      unstable ankles during inversion, eversion, plantar flexion, and dorsiflexion.
      DESIGN: Case-control study. SETTING: Athletic training research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Twenty participants with a history of "giving
      way" were included in the FAI group. Inclusion criteria for the FAI group
      included a history of at least 1 ankle sprain and repeated episodes of giving
      way. Twenty participants with no prior history of ankle injury were included in
      the control group. INTERVENTION(S): Isokinetic eccentric torque was assessed in
      each participant. MAIN OUTCOME MEASURE(S): Isokinetic eccentric testing was
      conducted for inversion-eversion and plantar-flexion-dorsiflexion movements. Peak
      torque values were standardized to each participant's body weight. The average of
      the 3 trials for each direction was used for statistical analysis. RESULTS: A
      significant side-by-group interaction was noted for eccentric plantar flexion
      torque (P < .01). Follow-up t tests revealed a significant difference between the
      FAI limb in the FAI group and the matched limb in the control group.
      Additionally, a significant difference was seen between the sides of the control
      group (P = .03). No significant interactions were identified for eccentric
      inversion, eversion, or dorsiflexion torques (P > .05). CONCLUSIONS: A deficit in
      plantar flexion torque was identified in the functionally unstable ankles. No
      deficits were identified for inversion, eversion, or dorsiflexion torque.
      Therefore, eccentric plantar flexion strength may be an important contributing
      factor to functional ankle instability.

PMID- 18335014
TI  - Thermoregulatory influence of a cooling vest on hyperthermic athletes.
AB  - CONTEXT: Athletic trainers must have sound evidence for the best practices in
      treating and preventing heat-related emergencies and potentially catastrophic
      events. OBJECTIVE: To examine the effectiveness of a superficial cooling vest on
      core body temperature (T(c)) and skin temperature (T(sk)) in hypohydrated
      hyperthermic male participants. DESIGN: A randomized control design with 2
      experimental groups. SETTING: Participants exercised by completing the heat
      stress trial in a hot, humid environment (ambient temperature = 33.1 +/- 3.1
      degrees C, relative humidity = 55.1 +/- 8.9%, wind speed = 2.1 +/- 1.1 km/hr)
      until a T(c) of 38.7 +/- 0.3 degrees C and a body mass loss of 3.27 +/- 0.1% were
      achieved. PATIENTS OR OTHER PARTICIPANTS: Ten healthy males (age = 25.6 +/- 1.6
      years, mass = 80.3 +/- 13.7 kg). INTERVENTION(S): Recovery in a thermoneutral
      environment wearing a cooling vest or without wearing a cooling vest until T(c)
      returned to baseline. MAIN OUTCOME MEASURE(S): Rectal T(c), arm T(sk), time to
      return to baseline T(c), and cooling rate. RESULTS: During the heat-stress trial,
      T(c) significantly increased (3.6%) and, at 30 minutes of recovery, T(c) had
      decreased significantly (2.6%) for both groups. Although not significant, the
      time for return to baseline T(c) was 22.6% faster for the vest group (43.8 +/-
      15.1 minutes) than for the no-vest group (56.6 +/- 18.0 minutes), and the cooling
      rate for the vest group (0.0298 +/- 0.0072 degrees C/min) was not significantly
      different from the cooling rate for the no-vest group (0.0280 +/- 0.0074 degrees
      C/min). The T(sk) during recovery was significantly higher (2.1%) in the vest
      group than in the no-vest group and was significantly lower (7.1%) at 30 minutes
      than at 0 minutes for both groups. CONCLUSIONS: We do not recommend using the
      cooling vest to rapidly reduce elevated T(c). Ice-water immersion should remain
      the standard of care for rapidly cooling severely hyperthermic individuals.

PMID- 18335015
TI  - Reliability and validity of an instrument to describe burnout among collegiate
      athletic trainers.
AB  - CONTEXT: The existing investigations of professional burnout among certified
      athletic trainers (ATs) were conducted before 2000. Since 2000, several
      educational and legal changes have redefined the job duties and responsibilities
      of the AT working in collegiate athletics. OBJECTIVE: To develop an instrument to
      determine factors that contribute to burnout in ATs employed within the
      collegiate athletics setting. DESIGN: Descriptive study. SETTING: National
      Collegiate Athletic Association (NCAA) Division I-A universities. PATIENTS OR
      OTHER PARTICIPANTS: Instrument design experts and ATs employed in various NCAA
      Division I-A athletic programs. MAIN OUTCOME MEASURE(S): The Athletic Training
      Burnout Inventory (ATBI) included the Maslach Burnout Inventory (18 items) plus
      45 new items to address established factors that lead to burnout and to address
      workload issues specific to athletic training. We initially developed 3
      constructs (emotional exhaustion and depersonalization, level of stress, and
      level of organizational support) and included them in the 2 field tests and first
      pilot test of the ATBI. For the second pilot test, the instrument comprised 4
      constructs: emotional exhaustion and depersonalization, administrative
      responsibility, time commitment, and organizational support. The 2 field tests
      were conducted to establish face and content validity of the ATBI. Reliability
      analyses were conducted twice on the 2 separate pilot tests using a Cronbach
      alpha set a priori at .70 and an item-to-total correlation. RESULTS: The second
      pilot test of the ATBI with the 4 constructs was determined reliable (emotional
      exhaustion and depersonalization, alpha = .85; administrative responsibility,
      alpha = .82; time commitment, alpha = .86; and organizational support, alpha =
      .80); however, some items within 2 constructs appeared suspect with low item-to
      total correlations (<0.25). CONCLUSIONS: The second administration of the ATBI
      produced an acceptable response rate. All 4 constructs were reliable; however,
      the suspect items within the constructs need further investigation. Researchers
      need to evaluate the conceptual worth of these items to the entire instrument.

PMID- 18335016
TI  - Choosing a career in athletic training: exploring the perceptions of potential
      recruits.
AB  - CONTEXT: The success of any academic program, including athletic training,
      depends upon attracting and keeping quality students. Therefore, understanding
      potential recruits' perceptions of athletic training is important. OBJECTIVE: To
      (1) gain insight regarding undergraduate students' decisions to enter or not
      enter an athletic training education program (ATEP), and (2) examine potential
      athletic training recruits' perceptions of the roles and responsibilities of
      certified athletic trainers. DESIGN: We used a descriptive study employing a
      grounded theory approach to explore perceptions of the athletic training
      profession by college students with various levels of interest in athletic
      training. SETTING: Athletic training education program from a National Collegiate
      Athletic Association Division I research-intensive university. PATIENTS OR OTHER
      PARTICIPANTS: Forty-six undergraduate students (23 interested in applying to an
      ATEP and 23 who were aware of but not interested in applying to an ATEP). MAIN
      OUTCOME MEASURE(S): Data from in-depth, semi-structured interviews were
      transcribed and analyzed using open, axial, and selective coding procedures.
      Member checks and peer-debriefing techniques were used to ensure trustworthiness
      of the study. RESULTS: Three contributing factors appeared to influence the
      recruitment of students to a career in athletic training: (1) a strong
      affiliation to a sports/team model, (2) initial exposure at the high school
      level, and (3) an incomplete understanding of athletic training. CONCLUSIONS:
      Awareness of how students are recruited into ATEPs is important information for
      our profession. Educators and administrators must create a comprehensive
      recruitment strategy using factors that influence potential recruits' decisions
      to enter the athletic training profession, specifically their association with
      sports and their experiences during high school.

PMID- 18335019
TI  - Alternatives for heart transplantation?

PMID- 18335020
TI  - Left ventricular assist device: a functional comparison with heart
      transplantation.
AB  - BACKGROUND: A growing number of patients with end-stage heart failure undergo
      implantation of ventricular assist devices as a bridge to heart transplantation.
      OBJECTIVES: In this study we investigated whether functional and haemodynamic
      recovery after implantation is sufficient to warrant the use of them as long-term
      alternative to heart transplantation. METHODS: We compared peak VO(2) of a group
      of patients three months after implantation of a ventricular assist device and
      three months after heart transplantation. Furthermore, we analysed the degree of
      haemodynamic recovery, by comparing plasma levels of BNP and creatinine before
      and after implantation of the device. RESULTS: After implantation of a
      ventricular assist device, exercise capacity improved considerably; three months
      after implantation peak VO(2) was 20.0+/-4.9 ml/kg/min (52% of predicted for age
      and gender). After heart transplantation exercise capacity improved even further;
      24.0+/-3.9 ml/ kg/min (62% of predicted for age and gender) (p<0.001). In the
      three months after implantation, BNP plasma levels decreased from 570+/-307
      pmol/l to 31+/-25 pmol/l and creatinine levels decreased from 191+/-82 mumol/l to
      82+/-25 mumol/l, indicating significant unloading of the ventricles and
      haemodynamic recovery. CONCLUSION: With regard to functional and haemodynamic
      recovery, the effect of implantation of a ventricular assist device is sufficient
      to justify its use as an alternative to heart transplantation. (Neth Heart J
      2008;16:41-6.).

PMID- 18335017
TI  - National athletic trainers' association position statement: preventing,
      detecting, and managing disordered eating in athletes.
AB  - OBJECTIVE: To present recommendations for the prevention, detection, and
      comprehensive management of disordered eating (DE) in athletes. BACKGROUND:
      Athletes with DE rarely self-report their symptoms. They tend to deny the
      condition and are often resistant to referral and treatment. Thus, screenings and
      interventions must be handled skillfully by knowledgeable professionals to obtain
      desired outcomes. Certified athletic trainers have the capacity and
      responsibility to play active roles as integral members of the health care team.
      Their frequent daily interactions with athletes help to facilitate the level of
      medical surveillance necessary for early detection, timely referrals, treatment
      follow-through, and compliance. RECOMMENDATIONS: These recommendations are
      intended to provide certified athletic trainers and others participating in the
      health maintenance and performance enhancement of athletes with specific
      knowledge and problem-solving skills to better prevent, detect, and manage DE.
      The individual biological, psychological, sociocultural, and familial factors for
      each athlete with DE result in widely different responses to intervention
      strategies, challenging the best that athletics programs have to offer in terms
      of resources and expertise. The complexity, time intensiveness, and expense of
      managing DE necessitate an interdisciplinary approach representing medicine,
      nutrition, mental health, athletic training, and athletics administration in
      order to facilitate early detection and treatment, make it easier for symptomatic
      athletes to ask for help, enhance the potential for full recovery, and satisfy
      medicolegal requirements. Of equal importance is establishing educational
      initiatives for preventing DE.

PMID- 18335021
TI  - Contrast-enhanced versus non-enhanced three-dimensional echocardiography of left
      ventricular volumes.
AB  - BACKGROUND: In three-dimensional echocardiography (3DE), individual endocardial
      trabeculae are not clearly visible necessitating left ventricular (LV) volumes to
      be measured by tracing the innermost endocardial contour. Ultrasound contrast
      agents aim to improve endocardial definition, but may delineate the outermost
      endocardial contour by filling up intertrabecular space. Although measurement
      reproducibility may benefit, there may be a significant influence on absolute LV
      volume measurements. METHODS: Twenty patients with a recent myocardial infarction
      and good ultrasound image quality underwent 3DE using the TomTec Freehand method
      before and during continuous intravenous contrast infusion. LV volumes were
      measured offline using TomTec Echo-Scan software. RESULTS: The use of contrast
      enhancement increased end-diastolic (110+/-35 vs. 144+/-53 ml; p<0.01) and end
      systolic volume measurements (68+/-31 vs. 87+/-45 ml; p<0.01) significantly
      compared with non-contrast; the ejection fraction remained unchanged (40+/-13 vs.
      41+/-14%, p=NS). Measurement reproducibility did not improve significantly,
      however. CONCLUSION: Volumes measured by 3DE are significantly larger when
      ultrasound contrast is used. Possibly, intertrabecular space comprises a
      substantial part of the LV cavity. In the presence of an adequate apical acoustic
      window, ultrasound contrast does not improve LV volume measurement
      reproducibility. (Neth Heart J 2008;16:47-52.).

PMID- 18335022
TI  - Remote monitoring in implantable defibrillator therapy.
AB  - The major device manufacturers have introduced systems for remote patient
      monitoring. These remote monitoring systems promise more efficient patient
      management, especially in today's clinical setting with the growing number of
      defibrillator implantations. The aim of this article is to present the role of
      remote patient monitoring in implantable cardioverter-defibrillator follow-up,
      its potential benefits and its barriers to widespread diffusion. (Neth Heart J
      2008;16:53-6.).

PMID- 18335023
TI  - Hypothyroidism as the cause of atrioventricular block in an elderly patient.
AB  - Syncope is a common problem in the older patient. Sometimes syncope is caused by
      extreme bradycardia secondary to atrioventricular (AV) block. We describe a case
      in which a 90-year-old woman presented with complete AV block due to severe
      hypothyroidism. After suppletion with levothyroxine, AV conduction was restored.
      (Neth Heart J 2008;16:57-9.).

PMID- 18335024
TI  - Ruptured sinus Valsalva aneurysm, a rare cause of heart failure.

PMID- 18335025
TI  - Direct isolation, culture and transplant of mouse skeletal muscle derived
      endothelial cells with angiogenic potential.
AB  - BACKGROUND: Although diseases associated with microvascular endothelial
      dysfunction are among the most prevalent illnesses to date, currently no method
      exists to isolate pure endothelial cells (EC) from skeletal muscle for in vivo or
      in vitro study. METHODOLOGY: By utilizing multicolor fluorescent-activated cell
      sorting (FACS), we have isolated a distinct population of Sca-1(+), CD31(+),
      CD34(dim) and CD45(- )cells from skeletal muscles of C57BL6 mice.
      Characterization of this population revealed these cells are functional EC that
      can be expanded several times in culture without losing their phenotype or
      capabilities to uptake acetylated low-density lipoprotein (ac-LDL), produce
      nitric oxide (NO) and form vascular tubes. When transplanted subcutaneously or
      intramuscularly into the tibialis anterior muscle, EC formed microvessels and
      integrated with existing vasculature. CONCLUSION: This method, which is highly
      reproducible, can be used to study the biology and role of EC in diseases such as
      peripheral vascular disease. In addition this method allows us to isolate large
      quantities of skeletal muscle derived EC with potential for therapeutic
      angiogenic applications.

PMID- 18335026
TI  - Osteopontin and systemic lupus erythematosus association: a probable gene-gender
      interaction.
AB  - Osteopontin (SPP1) is an important bone matrix mediator found to have key roles
      in inflammation and immunity. SPP1 genetic polymorphisms and increased
      osteopontin protein levels have been reported to be associated with SLE in small
      patient collections. The present study evaluates association between SPP1
      polymorphisms and SLE in a large cohort of 1141 unrelated SLE patients [707
      European-American (EA) and 434 African-American (AA)], and 2009 unrelated
      controls (1309 EA and 700 AA). Population-based case-control association analyses
      were performed. To control for potential population stratification, admixture
      adjusted logistic regression, genomic control (GC), structured association
      (STRAT), and principal components analysis (PCA) were applied. Combined analysis
      of 2 ethnic groups, showed the minor allele of 2 SNPs (rs1126616T and rs9138C)
      significantly associated with higher risk of SLE in males (P = 0.0005, OR = 1.73,
      95% CI = 1.28-2.33), but not in females. Indeed, significant gene-gender
      interactions in the 2 SNPs, rs1126772 and rs9138, were detected (P = 0.001 and P
      = 0.0006, respectively). Further, haplotype analysis identified rs1126616T
      rs1126772A-rs9138C which demonstrated significant association with SLE in general
      (P = 0.02, OR = 1.30, 95%CI 1.08-1.57), especially in males (P = 0.0003, OR =
      2.42, 95%CI 1.51-3.89). Subgroup analysis with single SNPs and haplotypes also
      identified a similar pattern of gender-specific association in AA and EA. GC,
      STRAT, and PCA results within each group showed consistent associations. Our data
      suggest SPP1 is associated with SLE, and this association is especially stronger
      in males. To our knowledge, this report serves as the first association of a
      specific autosomal gene with human male lupus.

PMID- 18335028
TI  - Laterality and flight: concurrent tests of side-bias and optimality in flying
      tree swallows.
AB  - Behavioural side-bias occurs in many vertebrates, including birds as a result of
      hemispheric specialization and can be advantageous by improving response times to
      sudden stimuli and efficiency in multi-tasking. However, behavioural side-bias
      can lead to morphological asymmetries resulting in reduced performance for
      specific activities. For flying animals, wing asymmetry is particularly costly
      and it is unclear if behavioural side-biases will be expressed in flight; the
      benefits of quick response time afforded by side-biases must be balanced against
      the costs of less efficient flight due to the morphological asymmetry side-biases
      may incur. Thus, competing constraints could lead to context-dependent expression
      or suppression of side-bias in flight. In repeated flight trials through an
      outdoor tunnel with obstacles, tree swallows (Tachycineta bicolor) preferred
      larger openings, but we did not detect either individual or population-level side
      biases. Thus, while observed behavioural side-biases during substrate-foraging
      and copulation are common in birds, we did not see such side-bias expressed in
      obstacle avoidance behaviour in flight. This finding highlights the importance of
      behavioural context for investigations of side-bias and hemispheric laterality
      and suggests both proximate and ultimate trade-offs between species-specific
      cognitive ecology and flight biomechanics.

PMID- 18335027
TI  - Association analysis of the FTO gene with obesity in children of Caucasian and
      African ancestry reveals a common tagging SNP.
AB  - Recently an association was demonstrated between the single nucleotide
      polymorphism (SNP), rs9939609, within the FTO locus and obesity as a consequence
      of a genome wide association (GWA) study of type 2 diabetes in adults. We
      examined the effects of two perfect surrogates for this SNP plus 11 other SNPs at
      this locus with respect to our childhood obesity cohort, consisting of both
      Caucasians and African Americans (AA). Utilizing data from our ongoing GWA study
      in our cohort of 418 Caucasian obese children (BMI>or=95th percentile), 2,270
      Caucasian controls (BMI<95th percentile), 578 AA obese children and 1,424 AA
      controls, we investigated the association of the previously reported variation at
      the FTO locus with the childhood form of this disease in both ethnicities. The
      minor allele frequencies (MAF) of rs8050136 and rs3751812 (perfect surrogates for
      rs9939609 i.e. both r(2) = 1) in the Caucasian cases were 0.448 and 0.443
      respectively while they were 0.391 and 0.386 in Caucasian controls respectively,
      yielding for both an odds ratio (OR) of 1.27 (95% CI 1.08-1.47; P = 0.0022).
      Furthermore, the MAFs of rs8050136 and rs3751812 in the AA cases were 0.449 and
      0.115 respectively while they were 0.436 and 0.090 in AA controls respectively,
      yielding an OR of 1.05 (95% CI 0.91-1.21; P = 0.49) and of 1.31 (95% CI 1.050
      1.643; P = 0.017) respectively. Investigating all 13 SNPs present on the Illumina
      HumanHap550 BeadChip in this region of linkage disequilibrium, rs3751812 was the
      only SNP conferring significant risk in AA. We have therefore replicated and
      refined the association in an AA cohort and distilled a tag-SNP, rs3751812, which
      captures the ancestral origin of the actual mutation. As such, variants in the
      FTO gene confer a similar magnitude of risk of obesity to children as to their
      adult counterparts and appear to have a global impact.

PMID- 18335029
TI  - Control of muscle mitochondria by insulin entails activation of Akt2-mtNOS
      pathway: implications for the metabolic syndrome.
AB  - BACKGROUND: In the metabolic syndrome with hyperinsulinemia, mitochondrial
      inhibition facilitates muscle fat and glycogen accumulation and accelerates its
      progression. In the last decade, nitric oxide (NO) emerged as a typical
      mitochondrial modulator by reversibly inhibiting citochrome oxidase and oxygen
      utilization. We wondered whether insulin-operated signaling pathways modulate
      mitochondrial respiration via NO, to alternatively release complete glucose
      oxidation to CO(2) and H(2)O or to drive glucose storage to glycogen.
      METHODOLOGY/PRINCIPAL FINDINGS: We illustrate here that NO produced by
      translocated nNOS (mtNOS) is the insulin-signaling molecule that controls
      mitochondrial oxygen utilization. We evoke a hyperinsulinemic-normoglycemic non
      invasive clamp by subcutaneously injecting adult male rats with long-lasting
      human insulin glargine that remains stable in plasma by several hours. At a
      precise concentration, insulin increased phospho-Akt2 that translocates to
      mitochondria and determines in situ phosphorylation and substantial cooperative
      mtNOS activation (+4-8 fold, P<.05), high NO, and a lowering of mitochondrial
      oxygen uptake and resting metabolic rate (-25 to -60%, P<.05). Comparing in vivo
      insulin metabolic effects on gastrocnemius muscles by direct electroporation of
      siRNA nNOS or empty vector in the two legs of the same animal, confirmed that in
      the silenced muscles disrupted mtNOS allows higher oxygen uptake and complete (U
      (14)C)-glucose utilization respect to normal mtNOS in the vector-treated ones
      (respectively 37+/-3 vs 10+/-1 micromolO(2)/h.g tissue and 13+/-1 vs 7.2+/-1
      micromol (3)H(2)O/h.g tissue, P<.05), which reciprocally restricted glycogen
      synthesis by a half. CONCLUSIONS/SIGNIFICANCE: These evidences show that after
      energy replenishment, insulin depresses mitochondrial respiration in skeletal
      muscle via NO which permits substrates to be deposited as macromolecules; at
      discrete hyperinsulinemia, persistent mtNOS activation could contribute to
      mitochondrial dysfunction with insulin resistance and obesity and therefore, to
      the progression of the metabolic syndrome.

PMID- 18335030
TI  - Quantitative trait loci for bone lengths on chromosome 5 using dual energy X-Ray
      absorptiometry imaging in the Twins UK cohort.
AB  - Human height is a highly heritable and complex trait but finding important genes
      has proven more difficult than expected. One reason might be the composite
      measure of height which may add heterogeneity and noise. The aim of this study
      was to conduct a genome-wide linkage scan to identify quantitative trait loci
      (QTL) for lengths of spine, femur, tibia, humerus and radius. These were
      investigated as alternative measures for height in a large, population-based twin
      sample with the potential to find genes underlying bone size and bone diseases.
      3,782 normal Caucasian females, 18-80 years old, with whole body dual energy X
      ray absorptiometry (DXA) images were used. A novel and reproducible method,
      linear pixel count (LPC) was used to measure skeletal sizes on DXA images.
      Intraclass correlations and heritability estimates were calculated for lengths of
      spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and
      dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000
      DZ twin subjects. All skeletal sites excluding spine were highly correlated.
      Intraclass correlations showed results for MZ twins to be significantly higher
      than DZ twins for all traits. Heritability results were as follows: spine, 66%;
      femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable
      evidence of highly suggestive linkage on chromosome 5 for spine (LOD score = 3.0)
      and suggestive linkage for femur (LOD score = 2.19) in the regions of 105cM and
      155cM respectively. We have shown strong heritability of all skeletal sizes
      measured in this study and provide preliminary evidence that spine length is
      linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be
      more useful than traditional height measures to uncover novel genes. Replication
      and further fine mapping of this region is ongoing to determine potential genes
      influencing bone size and diseases affecting bone.

PMID- 18335031
TI  - The impact of the human DNA topoisomerase II C-terminal domain on activity.
AB  - BACKGROUND: Type II DNA topoisomerases (topos) are essential enzymes needed for
      the resolution of topological problems that occur during DNA metabolic processes.
      Topos carry out an ATP-dependent strand passage reaction whereby one double helix
      is passed through a transient break in another. Humans have two topoII isoforms,
      alpha and beta, which while enzymatically similar are differentially expressed
      and regulated, and are thought to have different cellular roles. The C-terminal
      domain (CTD) of the enzyme has the most diversity, and has been implicated in
      regulation. We sought to investigate the impact of the CTD domain on activity.
      METHODOLOGY/PRINCIPLE FINDINGS: We have investigated the role of the human topoII
      C-terminal domain by creating constructs encoding C-terminally truncated
      recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha
      tail chimeric proteins. We then investigated function in vivo in a yeast system,
      and in vitro in activity assays. We find that the C-terminal domain of human
      topoII isoforms is needed for in vivo function of the enzyme, but not needed for
      cleavage activity. C-terminally truncated enzymes had similar strand passage
      activity to full length enzymes, but the presence of the opposite C-terminal
      domain had a large effect, with the topoIIalpha-CTD increasing activity, and the
      topoIIbeta-CTD decreasing activity. CONCLUSIONS/SIGNIFICANCE: In vivo
      complementation data show that the topoIIalpha C-terminal domain is needed for
      growth, but the topoIIbeta isoform is able to support low levels of growth
      without a C-terminal domain. This may indicate that topoIIbeta has an additional
      localisation signal. In vitro data suggest that, while the lack of any C-terminal
      domain has little effect on activity, the presence of either the topoIIalpha or
      beta C-terminal domain can affect strand passage activity. Data indicates that
      the topoIIbeta-CTD may be a negative regulator. This is the first report of in
      vitro data with chimeric human topoIIs.

PMID- 18335032
TI  - DICER-LIKE2 plays a primary role in transitive silencing of transgenes in
      Arabidopsis.
AB  - Dicer-like (DCL) enzymes play a pivotal role in RNA silencing in plants,
      processing the long double-stranded RNA (dsRNA) that triggers silencing into the
      primary short interfering RNAs (siRNAs) that mediate it. The siRNA population can
      be augmented and silencing amplified via transitivity, an RNA-dependent RNA
      polymerase (RDR)-dependent pathway that uses the target RNA as substrate to
      generate secondary siRNAs. Here we report that Arabidopsis DCL2-but not DCL4-is
      required for transitivity in cell-autonomous, post-transcriptional silencing of
      transgenes. An insertion mutation in DCL2 blocked sense transgene-induced
      silencing and eliminated accumulation of the associated RDR-dependent siRNAs. In
      hairpin transgene-induced silencing, the dcl2 mutation likewise eliminated
      accumulation of secondary siRNAs and blocked transitive silencing, but did not
      block silencing mediated by primary siRNAs. Strikingly, in all cases, the dcl2
      mutation eliminated accumulation of all secondary siRNAs, including those
      generated by other DCL enzymes. In contrast, mutations in DCL4 promoted a
      dramatic shift to transitive silencing in the case of the hairpin transgene and
      enhanced silencing induced by the sense transgene. Suppression of hairpin and
      sense transgene silencing by the P1/HC-Pro and P38 viral suppressors was
      associated with elimination of secondary siRNA accumulation, but the suppressors
      did not block processing of the stem of the hairpin transcript into primary
      siRNAs. Thus, these viral suppressors resemble the dcl2 mutation in their effects
      on siRNA biogenesis. We conclude that DCL2 plays an essential, as opposed to
      redundant, role in transitive silencing of transgenes and may play a more
      important role in silencing of viruses than currently thought.

PMID- 18335033
TI  - Screen for localized proteins in Caulobacter crescentus.
AB  - Precise localization of individual proteins is required for processes such as
      motility, chemotaxis, cell-cycle progression, and cell division in bacteria, but
      the number of proteins that are localized in bacterial species is not known. A
      screen based on transposon mutagenesis and fluorescence activated cell sorting
      was devised to identify large numbers of localized proteins, and employed in
      Caulobacter crescentus. From a sample of the clones isolated in the screen,
      eleven proteins with no previously characterized localization in C. crescentus
      were identified, including six hypothetical proteins. The localized hypothetical
      proteins included one protein that was localized in a helix-like structure, and
      two proteins for which the localization changed as a function of the cell cycle,
      suggesting that complex three-dimensional patterns and cell cycle-dependent
      localization are likely to be common in bacteria. Other mutants produced
      localized fusion proteins even though the transposon has inserted near the 5' end
      of a gene, demonstrating that short peptides can contain sufficient information
      to localize bacterial proteins. The screen described here could be used in most
      bacterial species.

PMID- 18335034
TI  - Transcriptional regulation of PIK3CA oncogene by NF-kappaB in ovarian cancer
      microenvironment.
AB  - PIK3CA upregulation, amplification and mutation have been widely reported in
      ovarian cancers and other tumors, which strongly suggests that PIK3CA is a
      promising therapeutic target. However, to date the mechanisms underlying PIK3CA
      regulation and activation in vivo is still unclear. During tumorigenesis, host
      tumor interactions may play a critical role in editing the tumor. Here, we report
      a novel mechanism through which the tumor microenvironment activates the PIK3CA
      oncogene. We show that PIK3CA upregulation occurs in non-proliferating tumor
      regions in vivo. We identified and characterized the PIK3CA 5' upstream
      transcriptional regulatory region and confirmed that PIK3CA is transcriptionally
      regulated through NF-kappaB pathway. These results offer a new mechanism through
      which the tumor microenvironment directly activates oncogenic pathways in tumor
      cells.

PMID- 18335035
TI  - SirT1 regulates energy metabolism and response to caloric restriction in mice.
AB  - The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well
      established roles in lifespan determination and response to caloric restriction.
      We have studied mice carrying two null alleles for SirT1, the mammalian
      orthologue of sir2, and found that these animals inefficiently utilize ingested
      food. These mice are hypermetabolic, contain inefficient liver mitochondria, and
      have elevated rates of lipid oxidation. When challenged with a 40% reduction in
      caloric intake, normal mice maintained their metabolic rate and increased their
      physical activity while the metabolic rate of SirT1-null mice dropped and their
      activity did not increase. Moreover, CR did not extend lifespan of SirT1-null
      mice. Thus, SirT1 is an important regulator of energy metabolism and, like its
      orthologues from simpler eukaryotes, the SirT1 protein appears to be required for
      a normal response to caloric restriction.

PMID- 18335036
TI  - Origins of spatial working memory deficits in schizophrenia: an event-related
      FMRI and near-infrared spectroscopy study.
AB  - Abnormal prefrontal functioning plays a central role in the working memory (WM)
      deficits of schizophrenic patients, but the nature of the relationship between WM
      and prefrontal activation remains undetermined. Using two functional neuroimaging
      methods, we investigated the neural correlates of remembering and forgetting in
      schizophrenic and healthy participants. We focused on the brain activation during
      WM maintenance phase with event-related functional magnetic resonance imaging
      (fMRI). We also examined oxygenated hemoglobin changes in relation to memory
      performance with the near-infrared spectroscopy (NIRS) using the same spatial WM
      task. Distinct types of correct and error trials were segregated for analysis.
      fMRI data indicated that prefrontal activation was increased during WM
      maintenance on correct trials in both schizophrenic and healthy subjects.
      However, a significant difference was observed in the functional asymmetry of
      frontal activation pattern. Healthy subjects showed increased activation in the
      right frontal, temporal and cingulate regions. Schizophrenic patients showed
      greater activation compared with control subjects in left frontal, temporal and
      parietal regions as well as in right frontal regions. We also observed increased
      'false memory' errors in schizophrenic patients, associated with increased
      prefrontal activation and resembling the activation pattern observed on the
      correct trials. NIRS data replicated the fMRI results. Thus, increased frontal
      activity was correlated with the accuracy of WM in both healthy control and
      schizophrenic participants. The major difference between the two groups concerned
      functional asymmetry; healthy subjects recruited right frontal regions during
      spatial WM maintenance whereas schizophrenic subjects recruited a wider network
      in both hemispheres to achieve the same level of memory performance. Increased
      "false memory" errors and accompanying bilateral prefrontal activation in
      schizophrenia suggest that the etiology of memory errors must be considered when
      comparing group performances. Finally, the concordance of fMRI and NIRS data
      supports NIRS as an alternative functional neuroimaging method for psychiatric
      research.

PMID- 18335037
TI  - The hippo pathway promotes Notch signaling in regulation of cell differentiation,
      proliferation, and oocyte polarity.
AB  - Specification of the anterior-posterior axis in Drosophila oocytes requires
      proper communication between the germ-line cells and the somatically derived
      follicular epithelial cells. Multiple signaling pathways, including Notch,
      contribute to oocyte polarity formation by controlling the temporal and spatial
      pattern of follicle cell differentiation and proliferation. Here we show that the
      newly identified Hippo tumor-suppressor pathway plays a crucial role in the
      posterior follicle cells in the regulation of oocyte polarity. Disruption of the
      Hippo pathway, including major components Hippo, Salvador, and Warts, results in
      aberrant follicle-cell differentiation and proliferation and dramatic disruption
      of the oocyte anterior-posterior axis. These phenotypes are related to defective
      Notch signaling in follicle cells, because misexpression of a constitutively
      active form of Notch alleviates the oocyte polarity defects. We also find that
      follicle cells defective in Hippo signaling accumulate the Notch receptor and
      display defects in endocytosis markers. Our findings suggest that the interaction
      between Hippo and classic developmental pathways such as Notch is critical to
      spatial and temporal regulation of differentiation and proliferation and is
      essential for development of the body axes in Drosophila.

PMID- 18335038
TI  - Hsp110 chaperones regulate prion formation and propagation in S. cerevisiae by
      two discrete activities.
AB  - The cytosolic chaperone network of Saccharomyces cerevisiae is intimately
      associated with the emergence and maintenance of prion traits. Recently, the
      Hsp110 protein, Sse1, has been identified as a nucleotide exchange factor (NEF)
      for both cytosolic Hsp70 chaperone family members, Ssa1 and Ssb1. We have
      investigated the role of Sse1 in the de novo formation and propagation of
      [PSI(+)], the prion form of the translation termination factor, Sup35. As
      observed by others, we find that Sse1 is essential for efficient prion
      propagation. Our results suggest that the NEF activity is required for
      maintaining sufficient levels of substrate-free Ssa1. However, Sse1 exhibits an
      additional NEF-independent activity; it stimulates in vitro nucleation of
      Sup35NM, the prion domain of Sup35. We also observe that high levels of Sse1, but
      not of an unrelated NEF, very potently inhibit Hsp104-mediated curing of
      [PSI(+)]. Taken together, these results suggest a chaperone-like activity of Sse1
      that assists in stabilization of early folding intermediates of the Sup35 prion
      conformation. This activity is not essential for prion formation under conditions
      of Sup35 overproduction, however, it may be relevant for spontaneous [PSI(+)]
      formation as well as for protection of the prion trait upon physiological Hsp104
      induction.

PMID- 18335039
TI  - The phylogeny of the four pan-American MtDNA haplogroups: implications for
      evolutionary and disease studies.
AB  - Only a limited number of complete mitochondrial genome sequences belonging to
      Native American haplogroups were available until recently, which left America as
      the continent with the least amount of information about sequence variation of
      entire mitochondrial DNAs. In this study, a comprehensive overview of all
      available complete mitochondrial DNA (mtDNA) genomes of the four pan-American
      haplogroups A2, B2, C1, and D1 is provided by revising the information scattered
      throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The
      phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub
      haplogroups but suggest that the ancestral Beringian population(s) contributed
      only six (successful) founder haplotypes to these haplogroups. The derived clades
      are overall starlike with coalescence times ranging from 18,000 to 21,000 years
      (with one exception) using the conventional calibration. The average of about
      19,000 years somewhat contrasts with the corresponding lower age of about 13,500
      years that was recently proposed by employing a different calibration and
      estimation approach. Our estimate indicates a human entry and spread of the pan
      American haplogroups into the Americas right after the peak of the Last Glacial
      Maximum and comfortably agrees with the undisputed ages of the earliest
      Paleoindians in South America. In addition, the phylogenetic approach also
      indicates that the pathogenic status proposed for various mtDNA mutations, which
      actually define branches of Native American haplogroups, was based on
      insufficient grounds.

PMID- 18335040
TI  - Fetuin-A induces cytokine expression and suppresses adiponectin production.
AB  - BACKGROUND: The secreted liver protein fetuin-A (AHSG) is up-regulated in hepatic
      steatosis and the metabolic syndrome. These states are strongly associated with
      low-grade inflammation and hypoadiponectinemia. We, therefore, hypothesized that
      fetuin-A may play a role in the regulation of cytokine expression, the modulation
      of adipose tissue expression and plasma concentration of the insulin-sensitizing
      and atheroprotective adipokine adiponectin. METHODOLOGY AND PRINCIPAL FINDINGS:
      Human monocytic THP1 cells and human in vitro differenttiated adipocytes as well
      as C57BL/6 mice were treated with fetuin-A. mRNA expression of the genes encoding
      inflammatory cytokines and the adipokine adiponectin (ADIPOQ) was assessed by
      real-time RT-PCR. In 122 subjects, plasma levels of fetuin-A, adiponectin and, in
      a subgroup, the multimeric forms of adiponectin were determined. Fetuin-A
      treatment induced TNF and IL1B mRNA expression in THP1 cells (p<0.05). Treatment
      of mice with fetuin-A, analogously, resulted in a marked increase in adipose
      tissue Tnf mRNA as well as Il6 expression (27- and 174-fold, respectively). These
      effects were accompanied by a decrease in adipose tissue Adipoq mRNA expression
      and lower circulating adiponectin levels (p<0.05, both). Furthermore, fetuin-A
      repressed ADIPOQ mRNA expression of human in vitro differentiated adipocytes
      (p<0.02) and induced inflammatory cytokine expression. In humans in plasma,
      fetuin-A correlated positively with high-sensitivity C-reactive protein, a marker
      of subclinical inflammation (r = 0.26, p = 0.01), and negatively with total- (r =
      -0.28, p = 0.02) and, particularly, high molecular weight adiponectin (r = -0.36,
      p = 0.01). CONCLUSIONS AND SIGNIFICANCE: We provide novel evidence that the
      secreted liver protein fetuin-A induces low-grade inflammation and represses
      adiponectin production in animals and in humans. These data suggest an important
      role of fatty liver in the pathophysiology of insulin resistance and
      atherosclerosis.

PMID- 18335041
TI  - Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial
      virus.
AB  - BACKGROUND: Bronchiolitis caused by the respiratory syncytial virus (RSV) in
      infants less than two years old is a growing public health concern worldwide, and
      there is currently no safe and effective vaccine. A major component of RSV
      nucleocapsid, the nucleoprotein (N), has been so far poorly explored as a
      potential vaccine antigen, even though it is a target of protective anti-viral T
      cell responses and is remarkably conserved between human RSV A and B serotypes.
      We recently reported a method to produce recombinant N assembling in homogenous
      rings composed of 10-11 N subunits enclosing a bacterial RNA. These nanoparticles
      were named sub-nucleocapsid ring structure (N SRS). METHODOLOGY AND PRINCIPAL
      FINDINGS: The vaccine potential of N SRS was evaluated in a well-characterized
      and widely acknowledged mouse model of RSV infection. BALB/c adult mice were
      immunized intranasally with N SRS adjuvanted with the detoxified E. coli
      enterotoxin LT(R192G). Upon RSV challenge, vaccinated mice were largely protected
      against virus replication in the lungs, with a mild inflammatory lymphocytic and
      neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited
      strong local and systemic immunity characterized by high titers of IgG1, IgG2a
      and IgA anti-N antibodies, antigen-specific CD8(+) T cells and IFN-gamma
      producing CD4(+) T cells. CONCLUSIONS/SIGNIFICANCE: This is the first report of
      using nanoparticles formed by the recombinant nucleocapsid protein as an
      efficient and safe intra-nasal vaccine against RSV.

PMID- 18335042
TI  - Prospects for malaria eradication in sub-Saharan Africa.
AB  - BACKGROUND: A characteristic of Plasmodium falciparum infections is the gradual
      acquisition of clinical immunity resulting from repeated exposures to the
      parasite. While the molecular basis of protection against clinical malaria
      remains unresolved, its effects on epidemiological patterns are well recognized.
      Accumulating epidemiological data constitute a valuable resource that must be
      intensively explored and interpreted as to effectively inform control planning.
      METHODOLOGY/PRINCIPAL FINDING: Here we apply a mathematical model to clinical
      data from eight endemic regions in sub-Saharan Africa. The model provides a
      quantitative framework within which differences in age distribution of clinical
      disease are assessed in terms of the parameters underlying transmission. The
      shorter infectious periods estimated for clinical infections induce a regime of
      bistability of endemic and malaria-free states in regions of mesoendemic
      transmission. The two epidemiological states are separated by a threshold that
      provides a convenient measure for intervention design. Scenarios of eradication
      and resurgence are simulated. CONCLUSIONS/SIGNIFICANCE: In regions that support
      mesoendemic transmission, intervention success depends critically on reducing
      prevalence below a threshold which separates endemic and malaria-free regimes.

PMID- 18335043
TI  - Molecular mapping of movement-associated areas in the avian brain: a motor theory
      for vocal learning origin.
AB  - Vocal learning is a critical behavioral substrate for spoken human language. It
      is a rare trait found in three distantly related groups of birds-songbirds,
      hummingbirds, and parrots. These avian groups have remarkably similar systems of
      cerebral vocal nuclei for the control of learned vocalizations that are not found
      in their more closely related vocal non-learning relatives. These findings led to
      the hypothesis that brain pathways for vocal learning in different groups evolved
      independently from a common ancestor but under pre-existing constraints. Here, we
      suggest one constraint, a pre-existing system for movement control. Using
      behavioral molecular mapping, we discovered that in songbirds, parrots, and
      hummingbirds, all cerebral vocal learning nuclei are adjacent to discrete brain
      areas active during limb and body movements. Similar to the relationships between
      vocal nuclei activation and singing, activation in the adjacent areas correlated
      with the amount of movement performed and was independent of auditory and visual
      input. These same movement-associated brain areas were also present in female
      songbirds that do not learn vocalizations and have atrophied cerebral vocal
      nuclei, and in ring doves that are vocal non-learners and do not have cerebral
      vocal nuclei. A compilation of previous neural tracing experiments in songbirds
      suggests that the movement-associated areas are connected in a network that is in
      parallel with the adjacent vocal learning system. This study is the first global
      mapping that we are aware for movement-associated areas of the avian cerebrum and
      it indicates that brain systems that control vocal learning in distantly related
      birds are directly adjacent to brain systems involved in movement control. Based
      upon these findings, we propose a motor theory for the origin of vocal learning,
      this being that the brain areas specialized for vocal learning in vocal learners
      evolved as a specialization of a pre-existing motor pathway that controls
      movement.

PMID- 18335044
TI  - Nucleotide sequence variation within the PI3K p85 alpha gene associates with
      alcohol risk drinking behaviour in adolescents.
AB  - BACKGROUND: While the phosphatidylinositol 3-kinase (PI3K)-dependent signaling
      pathway is typically known to regulate cell growth and survival, emerging
      evidence suggest a role for this pathway in regulating the behavioural responses
      to addictive drugs. METHODOLOGY/PRINCIPAL FINDINGS: To investigate whether PI3K
      contributes to patterns of risky alcohol drinking in human, we investigated
      genetic variations in PIK3R1, encoding the 85 kD regulatory subunit of PIK, in
      145 family trios consisting of 15-16 year old adolescents and their parents.
      Screening for mutations in exons, exon-intron boundaries and regulatory
      sequences, we identified 14 single nucleotide polymorphisms (SNPs) in the PIK3R1
      gene region from exon 1 to the beginning of the 3' untranslated region (UTR).
      These SNPs defined haplotypes for the respective PIK3R1 region. Four haplotype
      tagging (ht)SNPs (rs706713, rs2302975, rs171649 and rs1043526), discriminating
      all haplotypes with a frequency >or=4.5% were identified. These htSNPs were used
      to genotype adolescents from the "Mannheim Study of Risk Children" (MARC).
      Transmission disequilibrium tests in these adolescents and their parents
      demonstrated sex-specific association of two SNPs, rs2302975 and rs1043526, with
      patterns of risky alcohol consumption in male adolescents, including lifetime
      prevalence of drunkenness (p = 0.0019 and 0.0379, respectively) and elevated
      maximum amount of drinking (p = 0.0020 and 0.0494, respectively), as a measure
      for binge drinking pattern. CONCLUSIONS/SIGNIFICANCE: Our findings highlight a
      previously unknown relevance of PIK3R1 genotypes for alcohol use disorders and
      might help discriminate individuals at risk for alcoholism.

PMID- 18335045
TI  - A novel non-lens betagamma-crystallin and trefoil factor complex from amphibian
      skin and its functional implications.
AB  - BACKGROUND: In vertebrates, non-lens betagamma-crystallins are widely expressed
      in various tissues, but their functions are unknown. The molecular mechanisms of
      trefoil factors, initiators of mucosal healing and being greatly involved in
      tumorigenesis, have remained elusive. PRINCIPAL FINDINGS: A naturally existing 72
      kDa complex of non-lens betagamma-crystallin (alpha-subunit) and trefoil factor
      (beta-subunit), named betagamma-CAT, was identified from frog Bombina maxima skin
      secretions. Its alpha-subunit and beta-subunit (containing three trefoil factor
      domains), with a non-covalently linked form of alphabeta(2), show significant
      sequence homology to ep37 proteins, a group of non-lens betagamma-crystallins
      identified in newt Cynops pyrrhogaster and mammalian trefoil factors,
      respectively. betagamma-CAT showed potent hemolytic activity on mammalian
      erythrocytes. The specific antiserum against each subunit was able to neutralize
      its hemolytic activity, indicating that the two subunits are functionally
      associated. betagamma-CAT formed membrane pores with a functional diameter about
      2.0 nm, leading to K(+) efflux and colloid-osmotic hemolysis. High molecular
      weight SDS-stable oligomers (>240-kDa) were detected by antibodies against the
      alpha-subunit with Western blotting. Furthermore, betagamma-CAT showed multiple
      cellular effects on human umbilical vein endothelial cells. Low dosages of
      betagamma-CAT (25-50 pM) were able to stimulate cell migration and wound healing.
      At high concentrations, it induced cell detachment (EC(50) 10 nM) and apoptosis.
      betagamma-CAT was rapidly endocytosed via intracellular vacuole formation. Under
      confocal microscope, some of the vacuoles were translocated to nucleus and
      partially fused with nuclear membrane. Bafilomycin A1 (a specific inhibitor of
      the vacuolar-type ATPase) and nocodazole (an agent of microtuble depolymerizing),
      while inhibited betagamma-CAT induced vacuole formation, significantly inhibited
      betagamma-CAT induced cell detachment, suggesting that betagamma-CAT endocytosis
      is important for its activities. CONCLUSIONS/SIGNIFICANCE: These findings
      illustrate novel cellular functions of non-lens betagamma-cyrstallins and action
      mechanism via association with trefoil factors, serving as clues for
      investigating the possible occurrence of similar molecules and action mechanisms
      in mammals.

PMID- 18335046
TI  - Positive feedback and noise activate the stringent response regulator rel in
      mycobacteria.
AB  - Phenotypic heterogeneity in an isogenic, microbial population enables a subset of
      the population to persist under stress. In mycobacteria, stresses like nutrient
      and oxygen deprivation activate the stress response pathway involving the two
      component system MprAB and the sigma factor, SigE. SigE in turn activates the
      expression of the stringent response regulator, rel. The enzyme polyphosphate
      kinase 1 (PPK1) regulates this pathway by synthesizing polyphosphate required for
      the activation of MprB. The precise manner in which only a subpopulation of
      bacterial cells develops persistence, remains unknown. Rel is required for
      mycobacterial persistence. Here we show that the distribution of rel expression
      levels in a growing population of mycobacteria is bimodal with two distinct peaks
      corresponding to low (L) and high (H) expression states, and further establish
      that a positive feedback loop involving the mprAB operon along with stochastic
      gene expression are responsible for the phenotypic heterogeneity. Combining
      single cell analysis by flow cytometry with theoretical modeling, we observe that
      during growth, noise-driven transitions take a subpopulation of cells from the L
      to the H state within a "window of opportunity" in time preceding the stationary
      phase. It is these cells which adapt to nutrient depletion in the stationary
      phase via the stringent response. We find evidence of hysteresis in the
      expression of rel in response to changing concentrations of PPK1. Hysteresis
      promotes robustness in the maintenance of the induced state. Our results provide,
      for the first time, evidence that bistability and stochastic gene expression
      could be important for the development of "heterogeneity with an advantage" in
      mycobacteria and suggest strategies for tackling tuberculosis like targeting
      transitions from the low to the high rel expression state.

PMID- 18335047
TI  - A novel Campylobacter jejuni sequence type from a culture-negative patient in the
      Gambia.
AB  - The introduction of molecular diagnostic methods is crucial for improved
      understanding of the aetiology and epidemiology of bacterial infections in
      communities in resource poor settings. A blood sample from a 7 month old patient
      diagnosed with malaria in 2001 in a Gambian outpatient clinic was reported as
      culture negative after it was subjected to traditional bacterial culture
      protocols. We re-addressed the analysis of the blood sample from this case more
      recently (after 6.5 years in archival storage) in pilot work establishing 16S
      rRNA PCR in our molecular laboratory. Initial 16S rRNA PCR results confirmed the
      presence of bacterial DNA in the sample. 16S rRNA sequence analysis identified
      the organism as Campylobacter spp. In light of the molecular evidence we
      successfully grew the organism using appropriate culture conditions and
      subsequently biochemically confirmed that the isolate was Campylobacter jejuni.
      PCR and DNA sequencing of a set of seven C. jejuni housekeeping genes and in
      silico Multilocus Sequence Typing (MLST) analysis revealed that the isolate
      exhibits a novel sequence type (ST) of C. jejuni (ST 2928) and belongs to ST-443
      clonal complex. This study demonstrates the potential for molecular tools to
      enhance the diagnosis of bacterial infections, which remain a major killer
      globally, not least in children in the developing world. Improvements in
      diagnostics are needed, and will be important not only for sick individuals but
      also for populations, where better measures of disease burden will contribute
      significantly to the improvement of public health policy.

PMID- 18335048
TI  - Circulating matrix metalloproteinase-9 is associated with cardiovascular risk
      factors in a middle-aged normal population.
AB  - BACKGROUND: Elevated levels of circulating matrix metalloproteinase-9 (MMP-9)
      have been demonstrated in patients with established coronary artery disease
      (CAD). The aim of this study was to analyse levels of MMP-9 in a population free
      from symptomatic CAD and investigate their associations with cardiovascular (CV)
      risk factors, including C-reactive protein (CRP). METHODS: A cross-sectional
      study was performed in a population based random sample aged 45-69 (n = 345, 50%
      women). MMP-9 levels were measured in EDTA-plasma using an ELISA-method. CV risk
      factors were measured using questionnaires and standard laboratory methods.
      RESULTS: Plasma MMP-9 was detectable in all participants, mean 38.9 ng/mL (SD
      22.1 ng/mL). Among individuals without reported symptomatic CAD a positive
      association (p<0.001) was seen, for both men and women, of MMP-9 levels regarding
      total risk load of eight CV risk factors i.e. blood pressure, dyslipidemia,
      diabetes, obesity, smoking, alcohol intake, physical activity and fruit and
      vegetable intake. The association was significant also after adjustment for CRP,
      and was not driven by a single risk factor alone. In regression models adjusted
      for age, sex, smoking, alcohol intake and CRP, elevated MMP-9 levels were
      independently positively associated with systolic blood pressure (p = 0.037),
      smoking (p<0.001), alcohol intake (p = 0.003) and CRP (p<0.001). The correlation
      coefficient between MMP-9 and CRP was r = 0.24 (p<0.001). CONCLUSIONS: In a
      population without reported symptomatic CAD, MMP-9 levels were associated with
      total CV risk load as well as with single risk factors. This was found also after
      adjustment for CRP.

PMID- 18335049
TI  - Haptic guidance improves the visuo-manual tracking of trajectories.
AB  - BACKGROUND: Learning to perform new movements is usually achieved by following
      visual demonstrations. Haptic guidance by a force feedback device is a recent and
      original technology which provides additional proprioceptive cues during visuo
      motor learning tasks. The effects of two types of haptic guidances-control in
      position (HGP) or in force (HGF)-on visuo-manual tracking ("following") of
      trajectories are still under debate. METHODOLOGY/PRINCIPALS FINDINGS: Three
      training techniques of haptic guidance (HGP, HGF or control condition, NHG,
      without haptic guidance) were evaluated in two experiments. Movements produced by
      adults were assessed in terms of shapes (dynamic time warping) and kinematics
      criteria (number of velocity peaks and mean velocity) before and after the
      training sessions. Trajectories consisted of two Arabic and two Japanese-inspired
      letters in Experiment 1 and ellipses in Experiment 2. We observed that the use of
      HGF globally improves the fluency of the visuo-manual tracking of trajectories
      while no significant improvement was found for HGP or NHG.
      CONCLUSION/SIGNIFICANCE: These results show that the addition of haptic
      information, probably encoded in force coordinates, play a crucial role on the
      visuo-manual tracking of new trajectories.

PMID- 18335050
TI  - The anti-proliferative effects of the CHFR depend on the forkhead associated
      domain, but not E3 ligase activity mediated by ring finger domain.
AB  - The CHFR protein comprises fork head associated- (FHA) and RING-finger (RF)
      domain and is frequently downregulated in human colon and gastric cancers up to
      50%. The loss of CHFR mRNA expression is a consequence of promoter methylation,
      suggesting a tumor suppressor role for this gene in gastrointestinal
      carcinogenesis. In terms of the biological functions of CHFR, it has been shown
      to activate cell cycle checkpoint when cells are treated with microtubule
      depolymerizing agents. Furthermore, CHFR was reported to have E3 ligase activity
      and promote ubiquitination and degradation of oncogenic proteins such as Aurora A
      and polo-like kinase 1. However, molecular pathways involved in the tumor
      suppressive function of CHFR are not yet clear since the two established roles of
      this protein are likely to inhibit cell growth. In this study, we have identified
      that the FHA domain of CHFR protein is critical for growth suppressive
      properties, whereas the RF and cysteine rich domains (Cys) are not required for
      this function. In contrast, the RF and Cys domains are essential for E3 ligase
      activity of CHFR. By the use of a cell cycle checkpoint assay, we also confirmed
      that the FHA domain of CHFR plays an important role in initiating a cell cycle
      arrest at G2/M, indicating a functional link exists between the anti
      proliferative effects and checkpoint function of this tumor suppressor protein
      via this domain. Collectively, our data show that the checkpoint function of the
      FHA domain of CHFR is a core component of anti-proliferative properties against
      the gastrointestinal carcinogenesis.

PMID- 18335051
TI  - Human skeletal muscle mitochondrial uncoupling is associated with cold induced
      adaptive thermogenesis.
AB  - BACKGROUND: Mild cold exposure and overfeeding are known to elevate energy
      expenditure in mammals, including humans. This process is called adaptive
      thermogenesis. In small animals, adaptive thermogenesis is mainly caused by
      mitochondrial uncoupling in brown adipose tissue and regulated via the
      sympathetic nervous system. In humans, skeletal muscle is a candidate tissue,
      known to account for a large part of the epinephrine-induced increase in energy
      expenditure. However, mitochondrial uncoupling in skeletal muscle has not
      extensively been studied in relation to adaptive thermogenesis in humans.
      Therefore we hypothesized that cold-induced adaptive thermogenesis in humans is
      accompanied by an increase in mitochondrial uncoupling in skeletal muscle.
      METHODOLOGY/PRINCIPAL FINDINGS: The metabolic response to mild cold exposure in
      11 lean, male subjects was measured in a respiration chamber at baseline and mild
      cold exposure. Skeletal muscle mitochondrial uncoupling (state 4) was measured in
      muscle biopsies taken at the end of the respiration chamber stays. Mild cold
      exposure caused a significant increase in 24h energy expenditure of 2.8% (0.32
      MJ/day, range of -0.21 to 1.66 MJ/day, p<0.05). The individual increases in
      energy expenditure correlated to state 4 respiration (p<0.02, R(2) = 0.50).
      CONCLUSIONS/SIGNIFICANCE: This study for the first time shows that in humans,
      skeletal muscle has the intrinsic capacity for cold induced adaptive
      thermogenesis via mitochondrial uncoupling under physiological conditions. This
      opens possibilities for mitochondrial uncoupling as an alternative therapeutic
      target in the treatment of obesity.

PMID- 18335052
TI  - Conservation patterns of HIV-1 RT connection and RNase H domains: identification
      of new mutations in NRTI-treated patients.
AB  - BACKGROUND: Although extensive HIV drug resistance information is available for
      the first 400 amino acids of its reverse transcriptase, the impact of
      antiretroviral treatment in C-terminal domains of Pol (thumb, connection and
      RNase H) is poorly understood. METHODS AND FINDINGS: We wanted to characterize
      conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF.
      Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal
      domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil,
      and analyzed 510 thumb and connection domain and 450 RNase H domain sequences
      collected from public HIV sequence databases, together with their treatment
      status and histories. Drug-naive and NRTI-treated datasets were compared for
      intra- and inter-group conservation, and differences were determined using
      Fisher's exact tests. One third of RT C-terminal residues were found to be
      conserved among group M variants. Three mutations were found exclusively in NRTI
      treated isolates. Nine mutations in the connection and 6 mutations in the RNase H
      were associated with NRTI treatment in subtype B. Some of them lay in or close to
      amino acid residues which contact nucleic acid or near the RNase H active site.
      Several of the residues pointed out herein have been recently associated to NRTI
      exposure or increase drug resistance to NRTI. CONCLUSIONS: This is the first
      comprehensive genotypic analysis of a large sequence dataset that describes NRTI
      related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the
      conservation of RT C-terminal domains may pave the way to more rational drug
      design initiatives targeting those regions.

PMID- 18335053
TI  - Topological analysis of MAPK cascade for kinetic ErbB signaling.
AB  - Ligand-induced homo- and hetero-dimer formation of ErbB receptors results in
      different biological outcomes irrespective of recruitment and activation of
      similar effector proteins. Earlier experimental research indicated that cells
      expressing both EGFR (epidermal growth factor receptor) and the ErbB4 receptor
      (E1/4 cells) induced E1/4 cell-specific B-Raf activation and higher extracellular
      signal-regulated kinase (ERK) activation, followed by cellular transformation,
      than cells solely expressing EGFR (E1 cells) in Chinese hamster ovary (CHO)
      cells. Since our experimental data revealed the presence of positive feedback by
      ERK on upstream pathways, it was estimated that the cross-talk/feedback pathway
      structure of the Raf-MEK-ERK cascade might affect ERK activation dynamics in our
      cell system. To uncover the regulatory mechanism concerning the ERK dynamics, we
      used topological models and performed parameter estimation for all candidate
      structures that possessed ERK-mediated positive feedback regulation of Raf. The
      structure that reliably reproduced a series of experimental data regarding signal
      amplitude and duration of the signaling molecules was selected as a solution. We
      found that the pathway structure is characterized by ERK-mediated positive
      feedback regulation of B-Raf and B-Raf-mediated negative regulation of Raf-1.
      Steady-state analysis of the estimated structure indicated that the amplitude of
      Ras activity might critically affect ERK activity through ERK-B-Raf positive
      feedback coordination with sustained B-Raf activation in E1/4 cells. However,
      Rap1 that positively regulates B-Raf activity might be less effective concerning
      ERK and B-Raf activity. Furthermore, we investigated how such Ras activity in
      E1/4 cells can be regulated by EGFR/ErbB4 heterodimer-mediated signaling. From a
      sensitivity analysis of the detailed upstream model for Ras activation, we
      concluded that Ras activation dynamics is dominated by heterodimer-mediated
      signaling coordination with a large initial speed of dimerization when the
      concentration of the ErbB4 receptor is considerably high. Such characteristics of
      the signaling cause the preferential binding of the Grb2-SOS complex to
      heterodimer-mediated signaling molecules.

PMID- 18335054
TI  - PAX4 enhances beta-cell differentiation of human embryonic stem cells.
AB  - BACKGROUND: Human embryonic stem cells (HESC) readily differentiate into an
      apparently haphazard array of cell types, corresponding to all three germ layers,
      when their culture conditions are altered, for example by growth in suspension as
      aggregates known as embryoid bodies (EBs). However, this diversity of
      differentiation means that the efficiency of producing any one particular cell
      type is inevitably low. Although pancreatic differentiation has been reported
      from HESC, practicable applications for the use of beta-cells derived from HESC
      to treat diabetes will only be possible once techniques are developed to promote
      efficient differentiation along the pancreatic lineages. METHODS AND FINDINGS:
      Here, we have tested whether the transcription factor, Pax4 can be used to drive
      the differentiation of HESC to a beta-cell fate in vitro. We constitutively over
      expressed Pax4 in HESCs by stable transfection, and used Q-PCR analysis,
      immunocytochemistry, ELISA, Ca(2+) microfluorimetry and cell imaging to assess
      the role of Pax4 in the differentiation and intracellular Ca(2+) homeostasis of
      beta-cells developing in embryoid bodies produced from such HESC. Cells
      expressing key beta-cell markers were isolated by fluorescence-activated cell
      sorting after staining for high zinc content using the vital dye, Newport Green.
      CONCLUSION: Constitutive expression of Pax4 in HESC substantially enhances their
      propensity to form putative beta-cells. Our findings provide a novel foundation
      to study the mechanism of pancreatic beta-cells differentiation during early
      human development and to help evaluate strategies for the generation of purified
      beta-cells for future clinical applications.

PMID- 18335056
TI  - Ovulation order mediates a trade-off between pre-hatching and post-hatching
      viability in an altricial bird.
AB  - Simultaneously dependent siblings often compete for parentally provided
      resources. This competition may lead to mortality, the probability of which may
      be a function, in part, of the individual offspring's production order. In birds,
      serial ovulation followed by hatching asynchrony of simultaneous dependents leads
      to differences in post-hatching survival that largely depend on ovulation
      (laying) order. This has led to the widespread assumption that early-laid eggs
      are of greater value and therefore should possess different maternally
      manipulated characteristics than later-laid eggs. However, this perspective
      ignores the potential effect of laying order on pre-hatching viability, an effect
      which some studies suggest should offset the effect of laying order on post
      hatching viability. I examined the relationship between laying order and hatching
      and fledging probability in wild, free-living Lincoln's sparrows (Melospiza
      lincolnii). In broods with complete hatching success, first-laid and therefore
      first-hatched offspring had the highest probability of fledging, and fledging
      probability declined with increasing laying order. However, first-laid eggs were
      less likely than later-laid eggs to hatch. This effect of laying order on pre
      hatching viability seemed to offset that on post-hatching viability, and,
      consistently, maternal investment in egg size varied little if at all with
      respect to laying order. These results suggest that ovulation order mediates a
      trade-off between pre-hatching and post-hatching viability and should encourage a
      re-evaluation of the solitary role post-embryonic survival often plays when
      researchers make assumptions about the value of propagules based on the order in
      which they are produced.

PMID- 18335055
TI  - Decreased expression of Sprouty2 in the dorsolateral prefrontal cortex in
      schizophrenia and bipolar disorder: a correlation with BDNF expression.
AB  - BACKGROUND: Current theories on the pathophysiology of schizophrenia suggest
      altered brain plasticity such as decreased neural proliferation and migration,
      delayed myelination, and abnormal synaptic modeling, in the brain of subjects
      with schizophrenia. Though functional alterations in BDNF, which plays important
      role in neuroplasticity, are implicated in many abnormalities found in
      schizophrenia, the regulatory mechanism(s) involved in the abnormal signaling of
      BDNF in schizophrenia is not clear. The present study investigated whether
      Sprouty2, a regulator of growth factor signaling, is abnormally expressed in
      schizophrenia, and is associated with the changes in BDNF mRNA in this disorder.
      The potential effect of antipsychotic drugs on Sprouty2 expression was tested in
      adult rats. METHODS AND FINDINGS: Sprouty2 and BDNF gene expression were analyzed
      in dorsolateral prefrontal cortex samples from the Stanley Array Collection.
      Quantitative real-time PCR analysis of RNA in 100 individuals (35 with
      schizophrenia, 31 with bipolar disorder, and 34 psychiatrically normal controls)
      showed significantly decreased expression of Sprouty2 and BDNF in both
      schizophrenia and bipolar disorder. Moreover, a significant correlation between
      these two genes existed in control, schizophrenia and bipolar subjects. Long-term
      treatment with antipsychotic drugs, haloperidol and olanzapine, showed
      differential effects on both Sprouty2 and BDNF mRNA and protein levels in the
      frontal cortex of rats. CONCLUSION: These findings demonstrating decreased
      expression of Sprouty2 associated with changes in BDNF, suggest the possibility
      that these decreases are secondary to treatment rather than to factors that are
      significant in the disease process of either schizophrenia and/or bipolar
      disorder. Further exploration of Sprouty2-related signal transduction pathways
      may be helpful to design novel treatment strategies for these disorders.

PMID- 18335057
TI  - A naturally occurring plant cysteine protease possesses remarkable toxicity
      against insect pests and synergizes Bacillus thuringiensis toxin.
AB  - When caterpillars feed on maize (Zea maize L.) lines with native resistance to
      several Lepidopteran pests, a defensive cysteine protease, Mir1-CP, rapidly
      accumulates at the wound site. Mir1-CP has been shown to inhibit caterpillar
      growth in vivo by attacking and permeabilizing the insect's peritrophic matrix
      (PM), a structure that surrounds the food bolus, assists in digestion and
      protects the midgut from microbes and toxins. PM permeabilization weakens the
      caterpillar defenses by facilitating the movement of other insecticidal proteins
      in the diet to the midgut microvilli and thereby enhancing their toxicity. To
      directly determine the toxicity of Mir1-CP, the purified recombinant enzyme was
      directly tested against four economically significant Lepidopteran pests in
      bioassays. Mir1-CP LC(50) values were 1.8, 3.6, 0.6, and 8.0 ppm for corn
      earworm, tobacco budworm, fall armyworm and southwestern corn borer,
      respectively. These values were the same order of magnitude as those determined
      for the Bacillus thuringiensis toxin Bt-CryIIA. In addition to being directly
      toxic to the larvae, 60 ppb Mir1-CP synergized sublethal concentrations of Bt
      CryIIA in all four species. Permeabilization of the PM by Mir1-CP probably
      provides ready access to Bt-binding sites on the midgut microvilli and increases
      its activity. Consequently, Mir1-CP could be used for controlling caterpillar
      pests in maize using non-transgenic approaches and potentially could be used in
      other crops either singly or in combination with Bt-toxins.

PMID- 18335058
TI  - Rural-urban differences in maternal responses to childhood fever in South East
      Nigeria.
AB  - BACKGROUND: Childhood fevers due to malaria remain a major cause of morbidity and
      mortality among under-five children in Nigeria. The degree of vulnerability
      perceived by mothers will affect their perception of the severity and threat of
      their child's fever and the patterns of health care use. This study was
      undertaken to compare maternal responses to childhood fever in urban and rural
      areas of Enugu, south east Nigeria. METHODOLOGY/PRINCIPAL FINDINGS: Data was
      collected with pre-tested interviewer-administered questionnaires from 276 and
      124 urban and rural households respectively. In each household, only one woman
      aged 15-49 years who had lived in each of the urban and rural communities for at
      least one year and had at least one child less than 5 years old was interviewed.
      Malaria was mentioned as the commonest cause of childhood fevers. Rural mothers
      were more likely to recognize danger signs and symptoms than urban mothers. Rural
      mothers use more of informal than formal health services, and there is more home
      management of the fever with urban than rural mothers. Chloroquine, ACT, SP and
      Paracetamol are the main drugs given at home for childhood fevers, but the rural
      mothers were more likely to use leftover drugs from previous treatment to treat
      the fevers than urban mothers. The urban respondents were also more likely to use
      a preventive measure. Urban mothers sought actions faster than rural mothers and
      the total cost of treatment was also higher in urban areas.
      CONCLUSIONS/SIGNIFICANCE: Both urban and rural mothers are aware that malaria is
      the major cause of childhood fevers. Although rural mothers recognize childhood
      fever and danger signs better than urban mothers, the urban mothers' responses to
      fever seem to be better than that for rural mothers. These responses and
      differences may be important for geographical targeting by policy makers for
      malaria interventions.

PMID- 18335059
TI  - Cardiomyocyte formation by skeletal muscle-derived multi-myogenic stem cells
      after transplantation into infarcted myocardium.
AB  - BACKGROUND: Cellular cardiomyoplasty for myocardial infarction has been developed
      using various cell types. However, complete differentiation and/or trans
      differentiation into cardiomyocytes have never occurred in these transplant
      studies, whereas functional contributions were reported. METHODS AND RESULTS:
      Skeletal muscle interstitium-derived CD34(+)/CD45(-) (Sk-34) cells were purified
      from green fluorescent protein transgenic mice by flowcytometory. Cardiac
      differentiation of Sk-34 cells was examined by in vitro clonal culture and co
      culture with embryonic cardiomyocytes, and in vivo transplantation into a nude
      rat myocardial infarction (MI) model (left ventricle). Lower relative expression
      of cardiomyogenic transcription factors, such as GATA-4, Nkx2-5, Isl-1, Mef2 and
      Hand2, was seen in clonal cell culture. However, vigorous expression of these
      factors was seen on co-culture with embryonic cardiomyocytes, together with
      formation of gap-junctions and synchronous contraction following sphere-like
      colony formation. At 4 weeks after transplantation of freshly isolated Sk-34
      cells, donor cells exhibited typical cardiomyocyte structure with formation of
      gap-junctions, as well as intercalated discs and desmosomes, between donor and
      recipient and/or donor and donor cells. Fluorescence in situ hybridization (FISH)
      analysis detecting the rat and mouse genomic DNA and immunoelectron microscopy
      using anti-GFP revealed donor-derived cells. Transplanted Sk-34 cells were
      incorporated into infarcted portions of recipient muscles and contributed to
      cardiac reconstitution. Significant improvement in left ventricular function, as
      evaluated by transthoracic echocardiography and micro-tip conductance catheter,
      was also observed. CONCLUSIONS AND SIGNIFICANCE: Skeletal muscle-derived
      multipotent Sk-34 cells that can give rise to skeletal and smooth muscle cells as
      reported previously, also give rise to cardiac muscle cells as multi-myogenic
      stem cells, and thus are a potential source for practical cellular
      cardiomyoplasty.

PMID- 18335060
TI  - Mitigation measures for pandemic influenza in Italy: an individual based model
      considering different scenarios.
AB  - BACKGROUND: Individual-based models can provide the most reliable estimates of
      the spread of infectious diseases. In the present study, we evaluated the
      diffusion of pandemic influenza in Italy and the impact of various control
      measures, coupling a global SEIR model for importation of cases with an
      individual based model (IBM) describing the Italian epidemic.
      METHODOLOGY/PRINCIPAL FINDINGS: We co-located the Italian population (57 million
      inhabitants) to households, schools and workplaces and we assigned travel
      destinations to match the 2001 census data. We considered different R(0 )values
      (1.4; 1.7; 2), evaluating the impact of control measures (vaccination, antiviral
      prophylaxis -AVP-, international air travel restrictions and increased social
      distancing). The administration of two vaccine doses was considered, assuming
      that first dose would be administered 1-6 months after the first world case, and
      different values for vaccine effectiveness (VE). With no interventions,
      importation would occur 37-77 days after the first world case. Air travel
      restrictions would delay the importation of the pandemic by 7-37 days. With an
      R(0 )of 1.4 or 1.7, the use of combined measures would reduce clinical attack
      rates (AR) from 21-31% to 0.3-4%. Assuming an R(0) of 2, the AR would decrease
      from 38% to 8%, yet only if vaccination were started within 2 months of the first
      world case, in combination with a 90% reduction in international air traffic,
      closure of schools/workplaces for 4 weeks and AVP of household and school/work
      close contacts of clinical cases. Varying VE would not substantially affect the
      results. CONCLUSIONS: This IBM, which is based on country-specific demographic
      data, could be suitable for the real-time evaluation of measures to be undertaken
      in the event of the emergence of a new pandemic influenza virus. All preventive
      measures considered should be implemented to mitigate the pandemic.

PMID- 18335061
TI  - Transcriptomic analyses reveal novel genes with sexually dimorphic expression in
      the zebrafish gonad and brain.
AB  - BACKGROUND: Our knowledge on zebrafish reproduction is very limited. We generated
      a gonad-derived cDNA microarray from zebrafish and used it to analyze large-scale
      gene expression profiles in adult gonads and other organs. METHODOLOGY/PRINCIPAL
      FINDINGS: We have identified 116638 gonad-derived zebrafish expressed sequence
      tags (ESTs), 21% of which were isolated in our lab. Following in silico
      normalization, we constructed a gonad-derived microarray comprising 6370 unique,
      full-length cDNAs from differentiating and adult gonads. Labeled targets from
      adult gonad, brain, kidney and 'rest-of-body' from both sexes were hybridized
      onto the microarray. Our analyses revealed 1366, 881 and 656 differentially
      expressed transcripts (34.7% novel) that showed highest expression in ovary,
      testis and both gonads respectively. Hierarchical clustering showed correlation
      of the two gonadal transcriptomes and their similarities to those of the brains.
      In addition, we have identified 276 genes showing sexually dimorphic expression
      both between the brains and between the gonads. By in situ hybridization, we
      showed that the gonadal transcripts with the strongest array signal intensities
      were germline-expressed. We found that five members of the GTP-binding septin
      gene family, from which only one member (septin 4) has previously been implicated
      in reproduction in mice, were all strongly expressed in the gonads.
      CONCLUSIONS/SIGNIFICANCE: We have generated a gonad-derived zebrafish cDNA
      microarray and demonstrated its usefulness in identifying genes with sexually
      dimorphic co-expression in both the gonads and the brains. We have also provided
      the first evidence of large-scale differential gene expression between female and
      male brains of a teleost. Our microarray would be useful for studying gonad
      development, differentiation and function not only in zebrafish but also in
      related teleosts via cross-species hybridizations. Since several genes have been
      shown to play similar roles in gonadogenesis in zebrafish and other vertebrates,
      our array may even provide information on genetic disorders affecting gonadal
      phenotypes and fertility in mammals.

PMID- 18335062
TI  - Attainment of brown adipocyte features in white adipocytes of hormone-sensitive
      lipase null mice.
AB  - BACKGROUND: Hormone-sensitive lipase (HSL) is expressed predominantly in adipose
      tissue, where it plays an important role in catecholamine-stimulated hydrolysis
      of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad
      substrate specificity and besides acylglycerides it hydrolyzes cholesteryl
      esters, retinyl esters and lipoidal esters. Despite its role in fatty acid
      mobilization, HSL null mice have been shown to be resistant to diet-induced
      obesity. METHODOLOGY/PRINCIPAL FINDINGS: Following a high-fat diet (HFD) regimen,
      energy expenditure, measured using indirect calorimetry, was increased in HSL
      null mice. White adipose tissue of HSL null mice was characterized by reduced
      mass and reduced protein expression of PPARgamma, a key transcription factor in
      adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to
      be positively correlated to the differentiation state of the adipocyte. The
      protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of
      brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice
      compared to wildtype littermates. Transmission electron microscopy revealed an
      increase in the size of mitochondria of white adipocytes of HSL null mice. The
      mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes,
      while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to
      wildtype littermates. Basal oxygen consumption was increased almost 3-fold in
      white adipose tissue of HSL null mice and was accompanied by increased uncoupling
      activity. CONCLUSIONS: These data suggest that HSL is involved in the
      determination of white versus brown adipocytes during adipocyte differentiation
      The exact mechanism(s) underlying this novel role of HSL remains to be
      elucidated, but it seems clear that HSL is required to sustain normal expression
      levels of pRb and RIP140, which both promote differentiation into the white,
      rather than the brown, adipocyte lineage.

PMID- 18335063
TI  - The orexigenic effect of ghrelin is mediated through central activation of the
      endogenous cannabinoid system.
AB  - INTRODUCTION: Ghrelin and cannabinoids stimulate appetite, this effect possibly
      being mediated by the activation of hypothalamic AMP-activated protein kinase
      (AMPK), a key enzyme in appetite and metabolism regulation. The cannabinoid
      receptor type 1 (CB1) antagonist rimonabant can block the orexigenic effect of
      ghrelin. In this study, we have elucidated the mechanism of the putative ghrelin
      cannabinoid interaction. METHODS: The effects of ghrelin and CB1 antagonist
      rimonabant in wild-type mice, and the effect of ghrelin in CB1-knockout animals,
      were studied on food intake, hypothalamic AMPK activity and endogenous
      cannabinoid content. In patch-clamp electrophysiology experiments the effect of
      ghrelin was assessed on the synaptic inputs in parvocellular neurons of the
      hypothalamic paraventricular nucleus, with or without the pre-administration of a
      CB1 antagonist or of cannabinoid synthesis inhibitors. RESULTS AND CONCLUSIONS:
      Ghrelin did not induce an orexigenic effect in CB1-knockout mice.
      Correspondingly, both the genetic lack of CB1 and the pharmacological blockade of
      CB1 inhibited the effect of ghrelin on AMPK activity. Ghrelin increased the
      endocannabinoid content of the hypothalamus in wild-type mice and this effect was
      abolished by rimonabant pre-treatment, while no effect was observed in CB1-KO
      animals. Electrophysiology studies showed that ghrelin can inhibit the excitatory
      inputs on the parvocellular neurons of the paraventricular nucleus, and that this
      effect is abolished by administration of a CB1 antagonist or an inhibitor of the
      DAG lipase, the enzyme responsible for 2-AG synthesis. The effect is also lost in
      the presence of BAPTA, an intracellular calcium chelator, which inhibits
      endocannabinoid synthesis in the recorded parvocellular neuron and therefore
      blocks the retrograde signaling exerted by endocannabinoids. In summary, an
      intact cannabinoid signaling pathway is necessary for the stimulatory effects of
      ghrelin on AMPK activity and food intake, and for the inhibitory effect of
      ghrelin on paraventricular neurons.

PMID- 18335064
TI  - Global identification of Myc target genes reveals its direct role in
      mitochondrial biogenesis and its E-box usage in vivo.
AB  - The Myc oncoprotein is a transcription factor involved in a variety of human
      cancers. Overexpression of Myc is associated with malignant transformation. In
      normal cells, Myc is induced by mitotic signals, and in turn, it regulates the
      expression of downstream target genes. Although diverse roles of Myc have been
      predicted from many previous studies, detailed functions of Myc targets are still
      unclear. By combining chromatin immunoprecipitation (ChIP) and promoter
      microarrays, we identified a total of 1469 Myc direct target genes, the majority
      of which are novel, in HeLa cells and human primary fibroblasts. We observed
      dramatic changes of Myc occupancy at its target promoters in foreskin fibroblasts
      in response to serum stimulation. Among the targets of Myc, 107 were nuclear
      encoded genes involved in mitochondrial biogenesis. Genes with important roles in
      mitochondrial replication and biogenesis, such as POLG, POLG2, and NRF1 were
      identified as direct targets of Myc, confirming a direct role for Myc in
      regulating mitochondrial biogenesis. Analysis of target promoter sequences
      revealed a strong preference for Myc occupancy at promoters containing one of
      several described consensus sequences, CACGTG, in vivo. This study thus sheds
      light on the transcriptional regulatory networks mediated by Myc in vivo.

PMID- 18335065
TI  - Expression of human nPTB is limited by extreme suboptimal codon content.
AB  - BACKGROUND: The frequency of synonymous codon usage varies widely between
      organisms. Suboptimal codon content limits expression of viral, experimental or
      therapeutic heterologous proteins due to limiting cognate tRNAs. Codon content is
      therefore often adjusted to match codon bias of the host organism. Codon content
      also varies between genes within individual mammalian species. However, little
      attention has been paid to the consequences of codon content upon translation of
      host proteins. METHODOLOGY/PRINCIPAL FINDINGS: In comparing the splicing
      repressor activities of transfected human PTB and its two tissue-restricted
      paralogs-nPTB and ROD1-we found that the three proteins were expressed at widely
      varying levels. nPTB was expressed at 1-3% the level of PTB despite similar
      levels of mRNA expression and 74% amino acid identity. The low nPTB expression
      was due to the high proportion of codons with A or U at the third codon position,
      which are suboptimal in human mRNAs. Optimization of the nPTB codon content, akin
      to the "humanization" of foreign ORFs, allowed efficient translation in vivo and
      in vitro to levels comparable with PTB. We were then able to demonstrate that all
      three proteins act as splicing repressors. CONCLUSIONS/SIGNIFICANCE: Our results
      provide a striking illustration of the importance of mRNA codon content in
      determining levels of protein expression, even within cells of the natural host
      species.

PMID- 18335066
TI  - T helper 1-inducing adjuvant protects against experimental
      paracoccidioidomycosis.
AB  - Immunostimulatory therapy is a promising approach to improving the treatment of
      systemic fungal infections such as paracoccidioidomycosis (PCM), whose drug
      therapy is usually prolonged and associated with toxic side effects and relapses.
      The current study was undertaken to determine if the injection of a T helper (Th)
      1-stimulating adjuvant in P. brasiliensis-infected mice could have a beneficial
      effect on the course of experimental PCM. For this purpose, mice were infected
      and treated with complete Freund's adjuvant (CFA), a well-established Th1
      experimental inductor, or incomplete Freund's adjuvant (IFA - control group) on
      day 20 postinfection. Four weeks after treatment, the CFA-treated mice presented
      a mild infection in the lungs characterized by absence of epithelioid cell
      granulomas and yeast cells, whereas the control mice presented multiple sites of
      focal epithelioid granulomas with lymphomonocytic halos circumscribing a high
      number of viable and nonviable yeast cells. In addition, CFA administration
      induced a 2.4 log reduction (>99%) in the fungal burden when compared to the
      control group, and led to an improvement of immune response, reversing the
      immunosuppression observed in the control group. The immunotherapy with Th1
      inducing adjuvant, approved to be used in humans, might be a valuable tool in the
      treatment of PCM and potentially useful to improve the clinical cure rate in
      humans.

PMID- 18335067
TI  - Infections with immunogenic trypanosomes reduce tsetse reproductive fitness:
      potential impact of different parasite strains on vector population structure.
AB  - The parasite Trypanosoma brucei rhodesiense and its insect vector Glossina
      morsitans morsitans were used to evaluate the effect of parasite clearance
      (resistance) as well as the cost of midgut infections on tsetse host fitness.
      Tsetse flies are viviparous and have a low reproductive capacity, giving birth to
      only 6-8 progeny during their lifetime. Thus, small perturbations to their
      reproductive fitness can have a major impact on population densities. We measured
      the fecundity (number of larval progeny deposited) and mortality in parasite
      resistant tsetse females and untreated controls and found no differences. There
      was, however, a typanosome-specific impact on midgut infections. Infections with
      an immunogenic parasite line that resulted in prolonged activation of the tsetse
      immune system delayed intrauterine larval development resulting in the production
      of fewer progeny over the fly's lifetime. In contrast, parasitism with a second
      line that failed to activate the immune system did not impose a fecundity cost.
      Coinfections favored the establishment of the immunogenic parasites in the
      midgut. We show that a decrease in the synthesis of Glossina Milk gland protein
      (GmmMgp), a major female accessory gland protein associated with larvagenesis,
      likely contributed to the reproductive lag observed in infected flies.
      Mathematical analysis of our empirical results indicated that infection with the
      immunogenic trypanosomes reduced tsetse fecundity by 30% relative to infections
      with the non-immunogenic strain. We estimate that a moderate infection prevalence
      of about 26% with immunogenic parasites has the potential to reduce tsetse
      populations. Potential repercussions for vector population growth, parasite-host
      coevolution, and disease prevalence are discussed.

PMID- 18335068
TI  - Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta
      analysis of comparative trials.
AB  - BACKGROUND: Neurocysticercosis, infection of the brain with larvae of Taenia
      solium (pork tapeworm), is one of several forms of human cysticercosis caused by
      this organism. We investigated the role of albendazole and praziquantel in the
      treatment of patients with parenchymal neurocysticercosis by performing a meta
      analysis of comparative trials of their effectiveness and safety. METHODS AND
      PRINCIPAL FINDINGS: We performed a search in the PubMed database, Cochrane
      Database of Controlled Trials, and in references of relevant articles. Six
      studies were included in the meta-analysis. Albendazole was associated with
      better control of seizures than praziquantel in the pooled data analysis, when
      the generic inverse variance method was used to combine the incidence of seizure
      control in the included trials (patients without seizures/[patients x years at
      risk]) (156 patients in 4 studies, point effect estimate [incidence rate ratio] =
      4.94, 95% confidence interval 2.45-9.98). In addition, albendazole was associated
      with better effectiveness than praziquantel in the total disappearance of cysts
      (335 patients in 6 studies, random effects model, OR = 2.30, 95% CI 1.06-5.00).
      There was no difference between albendazole and praziquantel in reduction of
      cysts, proportion of patients with adverse events, and development of
      intracranial hypertension due to the administered therapy. CONCLUSIONS: A
      critical review of the available data from comparative trials suggests that
      albendazole is more effective than praziquantel regarding clinically important
      outcomes in patients with neurocysticercosis. Nevertheless, given the relative
      scarcity of trials, more comparative interventional studies--especially
      randomized controlled trials--are required to draw a safe conclusion about the
      best regimen for the treatment of patients with parenchymal neurocysticercosis.

PMID- 18335070
TI  - Early-life arsenic exposure: methylation capacity and beyond.

PMID- 18335069
TI  - Decision tree algorithms predict the diagnosis and outcome of dengue fever in the
      early phase of illness.
AB  - BACKGROUND: Dengue is re-emerging throughout the tropical world, causing frequent
      recurrent epidemics. The initial clinical manifestation of dengue often is
      confused with other febrile states confounding both clinical management and
      disease surveillance. Evidence-based triage strategies that identify individuals
      likely to be in the early stages of dengue illness can direct patient
      stratification for clinical investigations, management, and virological
      surveillance. Here we report the identification of algorithms that differentiate
      dengue from other febrile illnesses in the primary care setting and predict
      severe disease in adults. METHODS AND FINDINGS: A total of 1,200 patients
      presenting in the first 72 hours of acute febrile illness were recruited and
      followed up for up to a 4-week period prospectively; 1,012 of these were
      recruited from Singapore and 188 from Vietnam. Of these, 364 were dengue RT-PCR
      positive; 173 had dengue fever, 171 had dengue hemorrhagic fever, and 20 had
      dengue shock syndrome as final diagnosis. Using a C4.5 decision tree classifier
      for analysis of all clinical, haematological, and virological data, we obtained a
      diagnostic algorithm that differentiates dengue from non-dengue febrile illness
      with an accuracy of 84.7%. The algorithm can be used differently in different
      disease prevalence to yield clinically useful positive and negative predictive
      values. Furthermore, an algorithm using platelet count, crossover threshold value
      of a real-time RT-PCR for dengue viral RNA, and presence of pre-existing anti
      dengue IgG antibodies in sequential order identified cases with sensitivity and
      specificity of 78.2% and 80.2%, respectively, that eventually developed
      thrombocytopenia of 50,000 platelet/mm(3) or less, a level previously shown to be
      associated with haemorrhage and shock in adults with dengue fever. CONCLUSION:
      This study shows a proof-of-concept that decision algorithms using simple
      clinical and haematological parameters can predict diagnosis and prognosis of
      dengue disease, a finding that could prove useful in disease management and
      surveillance.

PMID- 18335071
TI  - Air pollution and birth weight in Connecticut and Massachusetts.

PMID- 18335073
TI  - Contribution of dental amalgam to urinary mercury excretion in children.

PMID- 18335076
TI  - Uncertainties in the relationship between tibia lead and cumulative blood lead
      index.

PMID- 18335078
TI  - Cancer and TCDD: the mitochondrial connection.

PMID- 18335080
TI  - Toxicity testing takes stock.

PMID- 18335081
TI  - Hard data for hard water.

PMID- 18335082
TI  - Dairy paradox.

PMID- 18335084
TI  - Synthetic turf: health debate takes root.

PMID- 18335085
TI  - Chemical reaction: the U.S. response to REACH.

PMID- 18335086
TI  - Dust storm fallout.

PMID- 18335087
TI  - Life after lindane in California.

PMID- 18335088
TI  - Prenatal lead exposure in mice.

PMID- 18335089
TI  - Taking a bite out of amalgam concerns?

PMID- 18335090
TI  - Fertility and markers of male reproductive function in Inuit and European
      populations spanning large contrasts in blood levels of persistent
      organochlorines.
AB  - OBJECTIVE: We synthesized the main findings from an international epidemiologic
      study on the impact of biopersistent organic pollutants (POPs) on human
      reproductive function. DATA SOURCES AND EXTRACTION: We used a database with
      interview and biological data from 2,269 women and their spouses, and 18
      published core papers. DATA SYNTHESIS: The study did not provide direct evidence
      of hormone-like activity of the polychlorinated biphenyl (PCB) congener CB-153
      and the main dichlorodiphenyltrichloroethane (DDT) metabolite, 1,1-dichloro-2,2
      bis(p-chlorophenyl)ethylene (p,p'-DDE), as serum concentrations of these
      compounds were not consistently related to either endogenous or exogenous hormone
      activity in serum. Nevertheless several links bewteen POP exposure and biomarkers
      of male reproductive function were identified. First, an association between high
      CB-153 serum levels and low sperm counts was detected within a subgroup of men
      with short androgen receptor CAG repeat length. Second, a relationship between
      increased CB-153 serum concentrations and decreased sperm motility was seen in
      all four studied regions, and indications of reduced neutral alpha-glucosidase
      activity in seminal plasma point to a post-testicular effect. Third, damage of
      sperm chromatin integrity was considerably less frequent in Greenlandic Inuits
      compared with that in European groups, and only in the latter was impairment of
      sperm chromatin integrity related to POPs. Despite these effects, fertility in
      terms of time taken to conceive was not related to POPs except in Inuits. A
      likely explanation of the latter was not identified. CONCLUSIONS: POPs may
      interfere with male reproductive function without major impact on fertility. The
      data do not provide direct evidence for endocrine disruption, hence other
      mechanisms should also be considered.

PMID- 18335091
TI  - Phytostabilization of mine tailings in arid and semiarid environments--an
      emerging remediation technology.
AB  - OBJECTIVE: Unreclaimed mine tailings sites are a worldwide problem, with
      thousands of unvegetated, exposed tailings piles presenting a source of
      contamination for nearby communities. Tailings disposal sites in arid and
      semiarid environments are especially subject to eolian dispersion and water
      erosion. Phytostabilization, the use of plants for in situ stabilization of
      tailings and metal contaminants, is a feasible alternative to costly remediation
      practices. In this review we emphasize considerations for phytostabilization of
      mine tailings in arid and semiarid environments, as well as issues impeding its
      long-term success. DATA SOURCES: We reviewed literature addressing mine closures
      and revegetation of mine tailings, along with publications evaluating plant
      ecology, microbial ecology, and soil properties of mine tailings. DATA
      EXTRACTION: Data were extracted from peer-reviewed articles and books identified
      in Web of Science and Agricola databases, and publications available through the
      U.S. Department of Agriculture, U.S. Environmental Protection Agency, and the
      United Nations Environment Programme. DATA SYNTHESIS: Harsh climatic conditions
      in arid and semiarid environments along with the innate properties of mine
      tailings require specific considerations. Plants suitable for phytostabilization
      must be native, be drought-, salt-, and metal-tolerant, and should limit shoot
      metal accumulation. Factors for evaluating metal accumulation and toxicity issues
      are presented. Also reviewed are aspects of implementing phytostabilization,
      including plant growth stage, amendments, irrigation, and evaluation.
      CONCLUSIONS: Phytostabilization of mine tailings is a promising remedial
      technology but requires further research to identify factors affecting its long
      term success by expanding knowledge of suitable plant species and mine tailings
      chemistry in ongoing field trials.

PMID- 18335092
TI  - Compound cytotoxicity profiling using quantitative high-throughput screening.
AB  - BACKGROUND: The propensity of compounds to produce adverse health effects in
      humans is generally evaluated using animal-based test methods. Such methods can
      be relatively expensive, low-throughput, and associated with pain suffered by the
      treated animals. In addition, differences in species biology may confound
      extrapolation to human health effects. OBJECTIVE: The National Toxicology Program
      and the National Institutes of Health Chemical Genomics Center are collaborating
      to identify a battery of cell-based screens to prioritize compounds for further
      toxicologic evaluation. METHODS: A collection of 1,408 compounds previously
      tested in one or more traditional toxicologic assays were profiled for
      cytotoxicity using quantitative high-throughput screening (qHTS) in 13 human and
      rodent cell types derived from six common targets of xenobiotic toxicity (liver,
      blood, kidney, nerve, lung, skin). Selected cytotoxicants were further tested to
      define response kinetics. RESULTS: qHTS of these compounds produced robust and
      reproducible results, which allowed cross-compound, cross-cell type, and cross
      species comparisons. Some compounds were cytotoxic to all cell types at similar
      concentrations, whereas others exhibited species- or cell type-specific
      cytotoxicity. Closely related cell types and analogous cell types in human and
      rodent frequently showed different patterns of cytotoxicity. Some compounds
      inducing similar levels of cytotoxicity showed distinct time dependence in
      kinetic studies, consistent with known mechanisms of toxicity. CONCLUSIONS: The
      generation of high-quality cytotoxicity data on this large library of known
      compounds using qHTS demonstrates the potential of this methodology to profile a
      much broader array of assays and compounds, which, in aggregate, may be valuable
      for prioritizing compounds for further toxicologic evaluation, identifying
      compounds with particular mechanisms of action, and potentially predicting in
      vivo biological response.

PMID- 18335093
TI  - Particle size distribution of airborne microorganisms and pathogens during an
      Intense African dust event in the eastern Mediterranean.
AB  - BACKGROUND: The distribution of microorganisms, and especially pathogens, over
      airborne particles of different sizes has been ignored to a large extent, but it
      could have significant implications regarding the dispersion of these
      microorganisms across the planet, thus affecting human health. OBJECTIVES: We
      examined the microbial quality of the aerosols over the eastern Mediterranean
      region during an African storm to determine the size distribution of
      microorganisms in the air. METHODS: We used a five-stage cascade impactor for
      bioaerosol collection in a coastal city on the eastern Mediterranean Sea during a
      north African dust storm. Bacterial communities associated with aerosol particles
      of six different size ranges were characterized following molecular culture
      independent methods, regardless of the cell culturability (analysis of 16S rRNA
      genes). RESULTS: All 16S rDNA clone libraries were diverse, including sequences
      commonly found in soil and marine ecosystems. Spore-forming bacteria such as
      Firmicutes dominated large particle sizes (> 3.3 microm), whereas clones
      affiliated with Actinobacteria (found commonly in soil) and Bacteroidetes (widely
      distributed in the environment) gradually increased their abundance in aerosol
      particles of reduced size (< 3.3 microm). A large portion of the clones detected
      at respiratory particle sizes (< 3.3 microm) were phylogenetic neighbors to human
      pathogens that have been linked to several diseases. CONCLUSIONS: The presence of
      aerosolized bacteria in small size particles may have significant implications to
      human health via intercontinental transportation of pathogens.

PMID- 18335094
TI  - Outcomes of the California ban on pharmaceutical lindane: clinical and ecologic
      impacts.
AB  - INTRODUCTION: There are increasing concerns over the presence and implications of
      pharmaceutical agents in water. In 2002, California banned pharmaceutical use of
      lindane because of concerns about water quality, as lindane treatment for head
      lice and scabies was found to be a significant factor adversely affecting
      wastewater quality. OBJECTIVES: In this article we describe the effects the ban
      has had on wastewater quality, unintentional exposures, and clinical practice.
      This is the first time that a pharmaceutical has been outlawed to protect water
      quality. As such, this ban provides a rare opportunity to evaluate the possible
      or potential outcomes of future public health interventions aimed at reducing
      pharmaceutical water contamination. METHODS: We compiled data on lindane in
      wastewater treatment plant effluent for several large plants in California and
      one outside of California. Data on exposures to lindane were obtained from
      records of the California Poison Control System. We assessed the impact on
      clinical practice via a survey of 400 pediatricians RESULTS: Wastewater treatment
      plant monitoring showed that lindane declined in California after the ban.
      Similarly, unintentional exposure calls declined. Most physicians were aware of
      the ban (81%) and had used lindane previously (61%), but they did not notice any
      difficulties with the ban (78%). CONCLUSIONS: The California experience suggests
      that elimination of pharmaceutical lindane produced environmental benefits, was
      associated with a reduction in reported unintentional exposures, and did not
      adversely affect head lice and scabies treatment. This ban serves as a model for
      governing bodies considering limits on the use of lindane or other
      pharmaceuticals.

PMID- 18335095
TI  - Urinary concentrations of triclosan in the U.S. population: 2003-2004.
AB  - BACKGROUND: Triclosan is a synthetic chemical with broad antimicrobial activity
      that has been used extensively in consumer products, including personal care
      products, textiles, and plastic kitchenware. OBJECTIVES: This study was designed
      to assess exposure to triclosan in a representative sample > or = 6 years of age
      of the U.S. general population from the 2003-2004 National Health and Nutrition
      Examination Survey (NHANES). METHODS: We analyzed 2,517 urine samples using
      automated solid-phase extraction coupled to isotope dilution-high-performance
      liquid chromatography-tandem mass spectrometry. RESULTS: We detected
      concentrations of total (free plus conjugated) triclosan in 74.6% of samples at
      concentrations of 2.4-3,790 microg/L. The geometric mean and 95th percentile
      concentrations were 13.0 microg/L (12.7 microg/g creatinine) and 459.0 microg/L
      (363.8 mug/g creatinine), respectively. We observed a curvilinear relation
      between age and adjusted least square geometric mean (LSGM) concentrations of
      triclosan. LSGM concentrations of triclosan were higher in people in the high
      household income than in people in low (p < 0.01) and medium (p = 0.04) income
      categories. CONCLUSIONS: In about three-quarters of urine samples analyzed as
      part of NHANES 2003-2004, we detected concentrations of triclosan. Concentrations
      differed by age and socioeconomic status but not by race/ethnicity and sex.
      Specifically, the concentrations of triclosan appeared to be highest during the
      third decade of life and among people with the highest household incomes.

PMID- 18335096
TI  - In utero and lactational exposures to low doses of polybrominated diphenyl ether
      47 alter the reproductive system and thyroid gland of female rat offspring.
AB  - BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are capable of disrupting
      thyroid hormone homeostasis. PBDE-47 (2,2',4,4'-tetrabromodiphenyl ether) is one
      of the most abundant congeners found in human breast adipose tissue and maternal
      milk samples. OBJECTIVES: We evaluated the effects of developmental exposure to
      low doses of PBDE-47 on the female reproductive system. METHODS: Pregnant Wistar
      rats were administered vehicle (peanut oil) or PBDE-47 [140 or 700 microg/kg body
      weight (bw)] on gestation day (GD) 6, or 5 mg 6-n-propyl-2-thiouracil (PTU)/L in
      the drinking water from GD7 through postnatal day (PND) 21. RESULTS: In female
      offspring sacrificed on PND38, there was a significant decrease in ovarian weight
      after exposure to PTU or 140 microg/kg PBDE-47. Alterations in folliculogenesis
      were apparent: we observed a decrease in tertiary follicles and serum estradiol
      concentrations in the offspring exposed to either PTU or 700 microg/kg PBDE-47.
      PTU exposure also resulted in a decrease in primordial follicles. On PND100,
      persistent effects on the thyroid glands included histologic and morphometric
      changes after exposure to either PTU or PBDE-47. No relevant changes in
      reproductive indices were observed after mating the exposed F1 females with
      nontreated males. CONCLUSIONS: Administration of PBDE-47 at doses relevant to
      human exposure led to changes in the rat female reproductive system and thyroid
      gland.

PMID- 18335097
TI  - Nutritional status has marginal influence on the metabolism of inorganic arsenic
      in pregnant Bangladeshi women.
AB  - BACKGROUND: The interindividual variation in metabolism of inorganic arsenic
      (iAs), involving methylation via one-carbon metabolism, has been well documented,
      but the reasons remain unclear. OBJECTIVES: In this population-based study we
      aimed to elucidate the effect of nutrition on As methylation among women in
      Matlab, Bangladesh, where people are chronically exposed to iAs via drinking
      water. METHODS: We studied effects of macronutrient status using body mass index
      (BMI) among 442 women in early pregnancy (gestational week 8), and effects of
      micronutrient status (plasma folate, vitamin B12, zinc, ferritin, and selenium)
      among 753 women at gestational week 14. Arsenic metabolites in urine were
      measured by HPLC combined with hydride generation inductively coupled plasma mass
      spectrometry. RESULTS: The median concentration of As in urine was 97 microg/L
      (range, 5-1,216 microg/L, adjusted by specific gravity). The average proportions
      of iAs, monomethylarsonic acid, and dimethylarsinic acid in urine in gestational
      week 8 were 15%, 11%, and 74%, respectively. Thus, the women had efficient As
      methylation in spite of being poorly nourished (one-third had BMIs < 18.5 kg/m2)
      and having elevated As exposure, both of which are known to decrease As
      methylation. The metabolism of iAs was only marginally influenced by
      micronutrient status, probably because women, especially in pregnancy and with
      low folate intake, have an efficient betaine-mediated remethylation of
      homocysteine, which is essential for an efficient As methylation. CONCLUSIONS: In
      spite of the high As exposure and prevalent malnutrition, overall As methylation
      in women in early pregnancy was remarkably efficient. The As exposure level had
      the greatest impact on As methylation among the studied factors.

PMID- 18335098
TI  - Low phytoestrogen levels in feed increase fetal serum estradiol resulting in the
      "fetal estrogenization syndrome" and obesity in CD-1 mice.
AB  - BACKGROUND: Although estrogenic chemicals can disrupt development of the
      reproductive system, there is debate about whether phytoestrogens in soy are
      beneficial, benign, or harmful. OBJECTIVES: We compared reproductive and
      metabolic characteristics in male and female mice reared and maintained on non
      soy low-phytoestrogen feed or soy-based high-phytoestrogen feed. METHODS: The low
      phytoestrogen diet was non-soy PMI 5K96 (verified casein diet), and the high
      phytoestrogen diet consisted of soy-based PMI 5008 during pregnancy and lactation
      and soy-based PMI 5001 maintenance feed after weaning. RESULTS: In fetuses whose
      mothers consumed the low-phytoestrogen PMI 5K96 feed, we found a paradoxical
      significant elevation in endogenous serum estradiol, which was associated
      postnatally with adverse reproductive outcomes referred to as the "fetal
      estrogenization syndrome (FES)". In females, this syndrome included early puberty
      and increased uterine responsiveness to estrogen, and in males, it included
      reduced testis, epididymis, and seminal vesicle size, but an enlarged prostate.
      The low-phytoestrogen-fed males and females were lighter at birth, but, between
      weaning and adulthood, they became obese and developed abnormally high serum
      leptin levels; these males, but not females, showed impaired glucose regulation.
      CONCLUSIONS: Removing phytoestrogens from mouse feed produces an obese phenotype
      consistent with metabolic syndrome, and the associated reproductive system
      abnormalities are consistent with FES due to elevated endogenous fetal estradiol.
      Laboratory rodents may have become adapted to high-phytoestrogen intake over many
      generations of being fed soy-based commercial feed; removing all phytoestrogens
      from feed leads to alterations that could disrupt many types of biomedical
      research.

PMID- 18335099
TI  - Hypertension and exposure to noise near airports: the HYENA study.
AB  - BACKGROUND: An increasing number of people are exposed to aircraft and road
      traffic noise. Hypertension is an important risk factor for cardiovascular
      disease, and even a small contribution in risk from environmental factors may
      have a major impact on public health. OBJECTIVES: The HYENA (Hypertension and
      Exposure to Noise near Airports) study aimed to assess the relations between
      noise from aircraft or road traffic near airports and the risk of hypertension.
      METHODS: We measured blood pressure and collected data on health, socioeconomic,
      and lifestyle factors, including diet and physical activity, via questionnaire at
      home visits for 4,861 persons 45-70 years of age, who had lived at least 5 years
      near any of six major European airports. We assessed noise exposure using
      detailed models with a resolution of 1 dB (5 dB for United Kingdom road traffic
      noise), and a spatial resolution of 250 x 250 m for aircraft and 10 x 10 m for
      road traffic noise. RESULTS: We found significant exposure-response relationships
      between night-time aircraft as well as average daily road traffic noise exposure
      and risk of hypertension after adjustment for major confounders. For night-time
      aircraft noise, a 10-dB increase in exposure was associated with an odds ratio
      (OR) of 1.14 [95% confidence interval (CI), 1.01-1.29]. The exposure-response
      relationships were similar for road traffic noise and stronger for men with an OR
      of 1.54 (95% CI, 0.99-2.40) in the highest exposure category (> 65 dB; p(trend) =
      0.008). CONCLUSIONS: Our results indicate excess risks of hypertension related to
      long-term noise exposure, primarily for night-time aircraft noise and daily
      average road traffic noise.

PMID- 18335100
TI  - Phthalate diesters and their metabolites in human breast milk, blood or serum,
      and urine as biomarkers of exposure in vulnerable populations.
AB  - BACKGROUND: Phthalates may pose a risk for perinatal developmental effects. An
      important question relates to the choice of suitable biological matrices for
      assessing exposure during this period. OBJECTIVES: This study was designed to
      measure the concentrations of phthalate diesters or their metabolites in breast
      milk, blood or serum, and urine and to evaluate their suitability for assessing
      perinatal exposure to phthalates. METHODS: In 2001, 2-3 weeks after delivery, 42
      Swedish primipara provided breast milk, blood, and urine samples at home. Special
      care was taken to minimize contamination with phthalates (e.g., use of a special
      breast milk pump, heat treatment of glassware and needles, addition of phosphoric
      acid). RESULTS: Phthalate diesters and metabolites in milk and blood or serum, if
      detected, were present at concentrations close to the limit of detection. By
      contrast, most phthalate metabolites were detectable in urine at concentrations
      comparable to those from the general population in the United States and in
      Germany. No correlations existed between urine concentrations and those found in
      milk or blood/serum for single phthalate metabolites. Our data are at odds with a
      previous study documenting frequent detection and comparatively high
      concentrations of phthalate metabolites in Finnish and Danish mothers' milk.
      CONCLUSIONS: Concentrations of phthalate metabolites in urine are more
      informative than those in milk or serum. Furthermore, collection of milk or blood
      may be associated with discomfort and potential technical problems such as
      contamination (unless oxidative metabolites are measured). Although urine is a
      suitable matrix for health-related phthalate monitoring, urinary concentrations
      in nursing mothers cannot be used to estimate exposure to phthalates through milk
      ingestion by breast-fed infants.

PMID- 18335101
TI  - Neonatal exposure to low doses of diazinon: long-term effects on neural cell
      development and acetylcholine systems.
AB  - BACKGROUND: The developmental neurotoxicity of organophosphate pesticides
      involves mechanisms other than their shared property of cholinesterase
      inhibition. OBJECTIVES: We gave diazinon (DZN) to newborn rats on postnatal days
      1-4, using doses (0.5 or 2 mg/kg) spanning the threshold for barely detectable
      cholinesterase inhibition. METHODS: We then evaluated the lasting effects on
      indices of neural cell number and size, and on functional markers of
      acetylcholine (ACh) synapses (choline acetyltransferase, presynaptic high
      affinity choline transporter, nicotinic cholinergic receptors) in a variety of
      brain regions. RESULTS: DZN exposure produced a significant overall increase in
      cell-packing density in adolescence and adulthood, suggestive of neuronal loss
      and reactive gliosis; however, some regions (temporal/occipital cortex, striatum)
      showed evidence of net cell loss, reflecting a greater sensitivity to neurotoxic
      effects of DZN. Deficits were seen in ACh markers in cerebrocortical areas and
      the hippocampus, regions enriched in ACh projections. In contrast, there were no
      significant effects in the midbrain, the major locus for ACh cell bodies. The
      striatum showed a unique pattern, with robust initial elevations in the ACh
      markers that regressed in adulthood to normal or subnormal values. CONCLUSIONS:
      These results indicate that developmental exposures to apparently nontoxic doses
      of DZN compromise neural cell development and alter ACh synaptic function in
      adolescence and adulthood. The patterns seen here differ substantially from those
      seen in earlier work with chlorpyrifos, reinforcing the concept that the various
      organophosphates have fundamentally different effects on the developmental
      trajectories of specific neurotransmitter systems, unrelated to their shared
      action as cholinesterase inhibitors.

PMID- 18335102
TI  - Direct, continuous monitoring of air pollution by transgenic sensor mice
      responsive to halogenated and polycyclic aromatic hydrocarbons.
AB  - BACKGROUND: The aryl hydrocarbon receptor (AhR, also called the dioxin receptor)
      plays crucial roles in toxicologic responses of animals to environmental
      pollutants, especially to halogenated and polycyclic aromatic hydrocarbons. To
      achieve direct, continuous risk assessment of air pollution using biological
      systems, we generated transgenic sensor mice that produce secreted alkaline
      phosphatase (SEAP) under the control of AhR. METHODS: To characterize responses
      of the mice to AhR agonists, sensor mice were orally administered 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), benzo[a]pyrene
      (B[a]P), or beta-naphthoflavone (BNF), and serum levels of SEAP were evaluated.
      To monitor air pollution caused by cigarette smoke, we placed the mice each day
      in an experimental smoking room, and evaluated activity of serum SEAP for up to 4
      days. Activation of AhR in individual organs was also examined by reverse
      transcription-polymerase chain reaction (RT-PCR) analysis of SEAP. RESULTS: In
      response to oral exposure to TCDD, sensor mice exhibited dramatic and sustained
      activation of AhR. The mice also responded sensitively to 3MC, B[a]P, and BNF.
      Activation of AhR was dose dependent, and the liver was identified as the main
      responding organ. After exposure to the smoking environment, sensor mice
      consistently exhibited transient, reversible activation of AhR. RT-PCR analysis
      of SEAP revealed that activation of AhR occurred predominantly in the lung.
      CONCLUSION: We are the first laboratory to demonstrate successfully direct,
      comprehensive monitoring of air pollution using genetically engineered mammals.
      The established system would be useful for real risk assessment of halogenated
      and polycyclic aromatic hydrocarbons in the air, especially in smoking
      environments.

PMID- 18335103
TI  - Low-level human equivalent gestational lead exposure produces sex-specific motor
      and coordination abnormalities and late-onset obesity in year-old mice.
AB  - BACKGROUND: Low-level developmental lead exposure is linked to cognitive and
      neurological disorders in children. However, the long-term effects of gestational
      lead exposure (GLE) have received little attention. OBJECTIVES: Our goals were to
      establish a murine model of human equivalent GLE and to determine dose-response
      effects on body weight, motor functions, and dopamine neurochemistry in year-old
      offspring. METHODS: We exposed female C57BL/6 mice to water containing 0, 27
      (low), 55 (moderate), or 109 ppm (high) of lead from 2 weeks prior to mating,
      throughout gestation, and until postnatal day 10 (PN10). Maternal and litter
      measures, blood lead concentrations ([BPb]), and body weights were obtained
      throughout the experiment. Locomotor behavior in the absence and presence of
      amphetamine, running wheel activity, rotarod test, and dopamine utilization were
      examined in year-old mice. RESULTS: Peak [BPb] were < 1, < or = 10, 24-27, and 33
      42 microg/dL in control, low-, moderate- and high-dose GLE groups at PN0-10,
      respectively. Year-old male but not female GLE mice exhibited late-onset obesity.
      Similarly, we observed male-specific decreased spontaneous motor activity,
      increased amphetamine-induced motor activity, and decreased rotarod performance
      in year-old GLE mice. Levels of dopamine and its major metabolite were altered in
      year-old male mice, although only forebrain utilization increased. GLE-induced
      alterations were consistently larger in low-dose GLE mice. CONCLUSIONS: Our novel
      results show that GLE produced permanent male-specific deficits. The nonmonotonic
      dose-dependent responses showed that low-level GLE produced the most adverse
      effects. These data reinforce the idea that lifetime measures of dose-response
      toxicant exposure should be a component of the neurotoxic risk assessment
      process.

PMID- 18335104
TI  - The effect of ambient air pollution during early pregnancy on fetal ultrasonic
      measurements during mid-pregnancy.
AB  - BACKGROUND: Over the past decade there has been mounting evidence that ambient
      air pollution during pregnancy influences fetal growth. OBJECTIVES: This study
      was designed to examine possible associations between fetal ultrasonic
      measurements collected from 15,623 scans (13-26 weeks gestation) and ambient air
      pollution during early pregnancy. METHODS: We calculated mothers' average monthly
      exposures over the first 4 months of pregnancy for the following pollutants:
      particulate matter < 10 microm aerodynamic diameter (PM10), ozone, nitrogen
      dioxide, and sulfur dioxide. We examined associations with fetal femur length
      (FL), biparietal diameter (BPD), head circumference (HC), and abdominal
      circumference (AC). Final analyses included scans from only those women within 2
      km of an air pollution monitoring site. We controlled for long-term trend,
      season, temperature, gestation, mother's age, socioeconomic status, and fetal
      sex. RESULTS: A reduction in fetal AC was associated with O3 during days 31-60 [
      1.42 mm; 95% confidence interval (CI), -2.74 to -0.09], SO2 during days 61-90 (
      1.67 mm; 95% CI, -2.94 to -0.40), and PM10 during days 91-120 (-0.78 mm; 95% CI, 
      1.49 to -0.08). Other results showed a reduction in BPD (-0.68 mm; 95% CI, -1.09
      to -0.27) associated with SO2 during days 0-30, a reduction in HC (-1.02 mm; 95%
      CI, -1.78 to -0.26) associated with PM10 during days 91-120, and a reduction in
      FL associated with PM10 during days 0-30 (-0.28 mm; 95% CI, -0.48 to -0.08) and
      91-120 (-0.23; 95% CI, -0.42 to -0.04). CONCLUSION: We found strong effects of
      ambient air pollution on ultrasound measures. Future research, including more
      individually detailed data, is needed to confirm our results.

PMID- 18335105
TI  - Temporal variation in the association between benzene and leukemia mortality.
AB  - BACKGROUND: Benzene is a human carcinogen. Exposure to benzene occurs in
      occupational and environmental settings. OBJECTIVE: I evaluated variation in
      benzene-related leukemia with age at exposure and time since exposure. METHODS: I
      evaluated data from a cohort of 1,845 rubber hydrochloride workers. Benzene
      exposure-leukemia mortality trends were estimated by applying proportional
      hazards regression methods. Temporal variation in the impact of benzene on
      leukemia rates was assessed via exposure time windows and fitting of a multistage
      cancer model. RESULTS: The association between leukemia mortality and benzene
      exposures was of greatest magnitude in the 10 years immediately after exposure
      [relative rate (RR) at 10 ppm-years = 1.19; 95% confidence interval (CI), 1.10
      1.29]; the association was of smaller magnitude in the period 10 to < 20 years
      after exposure (RR at 10 ppm-years = 1.05; 95% CI, 0.97-1.13); and there was no
      evidence of association > or = 20 years after exposure. Leukemia was more
      strongly associated with benzene exposures accrued at > or = 45 years of age (RR
      at 10 ppm-years = 1.11; 95% CI, 1.04-1.17) than with exposures accrued at younger
      ages (RR at 10 ppm-years = 1.01; 95% CI, 0.92-1.09). Jointly, these temporal
      effects can be efficiently modeled as a multistage process in which benzene
      exposure affects the penultimate stage in disease induction. CONCLUSIONS: Further
      attention should be given to evaluating the susceptibility of older workers to
      benzene-induced leukemia.

PMID- 18335106
TI  - Effect of inhaled carbon ultrafine particles on reactive hyperemia in healthy
      human subjects.
AB  - BACKGROUND: Ultrafine particles (UFP) may contribute to the cardiovascular
      effects of exposure to particulate air pollution, partly because of their
      relatively efficient alveolar deposition and potential to enter the pulmonary
      vascular space. OBJECTIVES: This study tested the hypothesis that inhalation of
      elemental carbon UFP alters systemic vascular function. METHODS: Sixteen healthy
      subjects (mean age, 26.9 +/- 6.5 years) inhaled air or 50 microg/m3 elemental
      carbon UFP by mouthpiece for 2 hr, while exercising intermittently. Measurements
      at preexposure baseline, 0 hr (immediately after exposure), 3.5 hr, 21 hr, and 45
      hr included vital signs, venous occlusion plethysmography and reactive hyperemia
      of the forearm, and venous plasma nitrate and nitrite levels. RESULTS: Peak
      forearm blood flow after ischemia increased 3.5 hr after exposure to air but not
      UFP (change from preexposure baseline, air: 9.31 +/- 3.41; UFP: 1.09 +/- 2.55
      mL/min/100 mL; t-test, p = 0.03). Blood pressure did not change, so minimal
      resistance after ischemia (mean blood pressure divided by forearm blood flow)
      decreased with air, but not UFP [change from preexposure baseline, air: -0.48 +/-
      0.21; UFP: 0.07 +/- 0.19 mmHg/mL/min; analysis of variance (ANOVA), p = 0.024].
      There was no UFP effect on pre-ischemia forearm blood flow or resistance, or on
      total forearm blood flow after ischemia. Venous nitrate levels were significantly
      lower after exposure to carbon UFP compared with air (ANOVA, p = 0.038). There
      were no differences in venous nitrite levels. CONCLUSIONS: Inhalation of 50
      microg/m3 carbon UFP during intermittent exercise impairs peak forearm blood flow
      during reactive hyperemia in healthy human subjects.

PMID- 18335107
TI  - Antigen sensitization influences organophosphorus pesticide-induced airway
      hyperreactivity.
AB  - BACKGROUND: Recent epidemiologic studies have identified organophosphorus
      pesticides (OPs) as environmental factors potentially contributing to the
      increase in asthma prevalence over the last 25 years. In support of this
      hypothesis, we have demonstrated that environmentally relevant concentrations of
      OPs induce airway hyperreactivity in guinea pigs. OBJECTIVES: Sensitization to
      allergen is a significant contributing factor in asthma, and we have shown that
      sensitization changes virus-induced airway hyperreactivity from an eosinophil
      independent mechanism to one mediated by eosinophils. Here, we determine whether
      sensitization similarly influences OP-induced airway hyperreactivity. METHODS:
      Nonsensitized and ovalbumin-sensitized guinea pigs were injected subcutaneously
      with the OP parathion (0.001-1.0 mg/kg). Twenty-four hours later, animals were
      anesthetized and ventilated, and bronchoconstriction was measured in response to
      either vagal stimulation or intravenous acetylcholine. Inflammatory cells and
      acetylcholinesterase activity were assessed in tissues collected immediately
      after physiologic measurements. RESULTS: Ovalbumin sensitization decreased the
      threshold dose for parathion-induced airway hyperreactivity and exacerbated
      parathion effects on vagally induced bronchoconstriction. Pretreatment with
      antibody to interleukin (IL)-5 prevented parathion-induced hyperreactivity in
      sensitized but not in nonsensitized guinea pigs. Parathion did not increase the
      number of eosinophils in airways or the number of eosinophils associated with
      airway nerves nor did it alter eosinophil activation as assessed by major basic
      protein deposition. CONCLUSIONS: Antigen sensitization increases vulnerability to
      parathion-induced airway hyperreactivity and changes the mechanism to one that is
      dependent on IL-5. Because sensitization to allergens is characteristic of 50% of
      the general population and 80% of asthmatics (including children), these findings
      have significant implications for OP risk assessment, intervention, and treatment
      strategies.

PMID- 18335108
TI  - Meeting report: batch-to-batch variability in estrogenic activity in commercial
      animal diets--importance and approaches for laboratory animal research.
AB  - We report information from two workshops sponsored by the National Institutes of
      Health that were held to a) assess whether dietary estrogens could significantly
      impact end points in experimental animals, and b) involve program participants
      and feed manufacturers to address the problems associated with measuring and
      eliminating batch-to-batch variability in rodent diets that may lead to
      conflicting findings in animal experiments within and between laboratories. Data
      were presented at the workshops showing that there is significant batch-to-batch
      variability in estrogenic content of commercial animal diets, and that this
      variability results in differences in experimental outcomes. A combination of
      methods were proposed to determine levels of total estrogenic activity and levels
      of specific estrogenic constituents in soy-containing, casein-containing, and
      other soy-free rodent diets. Workshop participants recommended that researchers
      pay greater attention to the type of diet being used in animal studies and choose
      a diet whose estrogenic activity (or lack thereof) is appropriate for the
      experimental model and end points of interest. Information about levels of
      specific phytoestrogens, as well as estrogenic activity caused by other
      contaminants and measured by bioassay, should be disclosed in scientific
      publications. This will require laboratory animal diet manufacturers to provide
      investigators with information regarding the phytoestrogen content and other
      estrogenic compounds in commercial diets used in animal research.

PMID- 18335109
TI  - Renal effects of dental amalgam in children: the New England children's amalgam
      trial.
AB  - BACKGROUND: Mercury is nephrotoxic and dental amalgam is a source of mercury
      exposure. METHODS: Children 6-10 years of age (n = 534) with two or more
      posterior teeth with caries but no prior amalgam restorations, were randomized to
      one of two treatments--amalgam or resin composite (white fillings)--used for
      caries treatment during 5 years of follow-up. The primary outcome was change in
      IQ, but important secondary outcomes were effects on markers of glomerular and
      tubular kidney function: urinary excretion of albumin, alpha-1-microglobulin
      (A1M), gamma-glutamyl transpeptidase (gamma-GT), and N-acetyl-beta-d
      glucosaminidase (NAG). These markers were measured on several occasions during
      the trial, together with urinary mercury and covariates. We evaluated the results
      using repeated-measures analyses. RESULTS: There were no significant differences
      between treatment groups in average levels of renal biomarkers, nor significant
      effects of number of dental amalgams on these markers. There was, however, a
      significantly increased prevalence of microalbuminuria (MA) among children in the
      amalgam group in years 3-5 (adjusted odds ratio 1.8; 95% confidence interval, 1.1
      2.9). Most of these cases are likely to be temporary MA, but 10 children in the
      amalgam group had MA in both years 3 and 5, versus 2 children in the composite
      group (p = 0.04). There were no differences in the occurrence of high levels of
      renal tubular markers (A1M, gamma-GT, or NAG). CONCLUSIONS: The increase in MA
      may be a random finding, but should be tested further. The results did not
      support recent findings in an observational study of an effect of low-level
      mercury on tubular biomarkers in children.

PMID- 18335110
TI  - Polybrominated diphenyl ethers (PBDEs) and bioaccumulative hydroxylated PBDE
      metabolites in young humans from Managua, Nicaragua.
AB  - OBJECTIVE: Our aim was to investigate exposure to polybrominated diphenyl ethers
      (PBDEs) in a young urban population in a developing country, with focus on
      potentially highly exposed children working informally as scrap scavengers at a
      large municipal waste disposal site. We also set out to investigate whether
      hydroxylated metabolites, which not hitherto have been found retained in humans,
      could be detected. METHODS: We assessed PBDEs in pooled serum samples obtained in
      2002 from children 11-15 years of age, working and sometimes also living at the
      municipal waste disposal site in Managua, and in nonworking urban children. The
      influence of fish consumption was evaluated in the children and in groups of
      women 15-44 years of age who differed markedly in their fish consumption.
      Hydroxylated PBDEs were assessed as their methoxylated derivates. The chemical
      analyses were performed by gas chromatography/mass spectrometry, using authentic
      reference substances. RESULTS: The children living and working at the waste
      disposal site showed very high levels of medium brominated diphenyl ethers. The
      levels observed in the referent children were comparable to contemporary
      observations in the United States. The exposure pattern was consistent with dust
      being the dominating source. The children with the highest PBDE levels also had
      the highest levels of hydroxylated metabolites. CONCLUSIONS: Unexpectedly, very
      high levels of PBDEs were found in children from an urban area in a developing
      country. Also, for the first time, hydroxylated PBDE metabolites were found to
      bioaccumulate in human serum.

PMID- 18335111
TI  - Glutathione S-transferase P1, maternal smoking, and asthma in children: a
      haplotype-based analysis.
AB  - BACKGROUND: Glutathione S-transferase P1 (GSTP1) plays a role in a spectrum of
      respiratory diseases; however, the effects of sequence variation across the
      entire locus in asthma pathogenesis have yet to be determined. OBJECTIVES: This
      study was designed to investigate whether sequence variations in the GSTP1 coding
      and promoter regions are associated with asthma and wheezing outcomes and to
      determine whether variants affect susceptibility to maternal smoking. METHODS:
      Four haplotype tagging SNPs were selected that accounted for 83% of the common
      haplotypic variation in GSTP1. The associations of GSTP1 variants with asthma and
      wheezing were assessed among white children in the Children's Health Study (CHS).
      RESULTS: The Ile105Val allele and a SNP in the upstream promoter region (SNP1:
      rs6591255, putative transcription factor 1 binding site) were associated with
      asthma and wheezing outcomes, an association observed in two cohorts of the CHS
      recruited in different years. Haplotypes that included both the promoter SNP
      (i.e., rs6591255) and the 105 Val variant were associated with an increased risk
      for asthma in non-Hispanic whites. Using SNP- and haplotype-based approaches, the
      effect of maternal smoking on wheezing was largest in children with the Ile105Val
      allele. CONCLUSIONS: Variants in both the promoter and coding regions of the
      GSTP1 locus may contribute to the occurrence of childhood asthma and wheezing and
      may increase susceptibility to adverse effects of tobacco-smoke exposure.

PMID- 18335112
TI  - Pilot studies of estrogen-related physical findings in infants.
AB  - BACKGROUND: Soy formula containing estrogenic isoflavones is widely used in the
      United States. Infants consuming soy formula exclusively have high isoflavone
      exposures. We wanted to study whether soy formula prolonged the physiologic
      estrogenization of newborns, but available quantitative descriptions of the
      natural history of breast and genital development are inadequate for study
      design. OBJECTIVE: We piloted techniques for assessing infants' responses to the
      withdrawal from maternal estrogen and gathered data on breast and genital
      development in infants at different ages. METHODS: We studied 37 boys and 35
      girls, from term pregnancies with normal birth weights, who were < 48 hr to 6
      months of age, and residents of Philadelphia, Pennsylvania, during 2004-2005. One
      third of the children of each sex and age interval were exclusively fed breast
      milk, soy formula, or cow-milk formula. Our cross-sectional study measured breast
      adipose tissue, breast buds, and testicular volume; observed breast and genital
      development; and collected vaginal wall cells and information on vaginal
      discharge. We assessed reliability of the measures. RESULTS: Breast tissue was
      maximal at birth and disappeared in older children, consistent with waning
      maternal estrogen. Genital development did not change by age. Breast-milk
      secretion and withdrawal bleeding were unusual. Vaginal wall cells showed maximal
      estrogen effect at birth and then reverted; girls on soy appeared to show
      reestrogenization at 6 months. CONCLUSIONS: Examination of infants for plausible
      effects of estrogens is valid and repeatable. Measurement of breast tissue and
      characterization of vaginal wall cells could be used to evaluate exposures with
      estrogen-like effects.

PMID- 18335113
TI  - Modeling studies of potato nucleoside triphosphate diphosphohydrolase NTPDase1:
      an insight into the catalytic mechanism.
AB  - Nucleoside triphosphate diphosphohydrolase--NTPDase1 (apyrase, EC 3.6.1.5) was
      modeled based on sequence homology. The single polypeptide chain of apyrase is
      folded into two domains. The putative catalytic site with the apyrase conserved
      regions (ACR 1-5) is located between these two domains. Modeling confirmed that
      apyrase belongs to the actin superfamily of proteins. The amino acids interacting
      with the nucleoside triphosphate substrate and probably involved in the catalyzed
      hydrolysis were identified. The proposed two-step catalytic mechanism of
      hydrolysis involves Thr127 and Thr55 as potential nucleophilic factors
      responsible for the cleavage of the Pgamma and Pbeta anhydride bonds,
      respectively. Their action seems to be assisted by Glu170 and Glu78 residues,
      respectively. The presence of two nucleophiles in the active site of apyrase
      explains the differences in the hydrolytic activity between apyrases and other
      enzymes belonging to the NTPDase family.

PMID- 18335114
TI  - Current opinion on drug-induced oral reactions: a comprehensive review.
AB  - AIM: The aim of this comprehensive review is to present an update to our previous
      review about drug-induced oral reactions. All drugs that may cause adverse
      effects in the mouth and related structures are reviewed. BACKGROUND: Every drug
      can produce untoward consequences even when used according to standard or
      recommended methods of administration. Adverse drug reactions can involve every
      organ and system of the body and are frequently mistaken for signs of underlying
      disease. The mouth and associated structures can also be affected by many drugs
      or chemicals. Good oral health including salivary function is very important in
      maintaining whole body health. Drug reactions can be categorized as to the parts
      of the oral complex such as the oral mucosa and tongue, periodontal tissues,
      dental structures, salivary glands, cleft lip and palate, muscles, and nerves.
      REVIEW RESULTS: This review suggests the number of drugs and chemicals that can
      produce adverse or toxic reactions in the oral cavity are on the rise. An updated
      listing of offending drugs is provided along with current strategies for dealing
      with adverse reactions. CONCLUSION: Clinicians must constantly update their
      knowledge of drugs used by their patients. Attention must be paid to their toxic
      and unwanted effects that in many cases may be similar to characteristics of
      common diseases. CLINICAL SIGNIFICANCE: Dentists and specialists of oral diseases
      should be aware of adverse drug oral reactions for better diagnosis of oral
      diseases, administration of drugs, and patient compliance during drug therapy.

PMID- 18335115
TI  - Dental caries in relation to salivary factors in Saudi population groups.
AB  - AIMS: The aim of this cross-sectional study was to register caries trends in
      relation to some risk factors such as oral hygiene, salivary level of
      streptococcus mutans (SM), lactobacilli (LB), yeast, salivary flow rate,
      buffering capacity, pH, and fluoride level among different age groups of a Saudi
      population. The study also aimed at determining which of the salivary factors
      correlate significantly to caries. METHODS AND MATERIALS: A random sample of 312
      subjects belonging to age groups six-11, 12-17, and 18-40 years were selected
      from patients attending the screening dental clinics of the Faculty of Dentistry,
      King Abdulaziz University in Jeddah, Saudi Arabia. Patients were examined
      clinically to measure the caries experience using decayed, missing, and filled
      teeth (DMFT) and oral hygiene levels using the Green and Vermillion method.
      Resting and stimulated saliva were collected to determine flow rate, fluoride,
      pH, buffering capacity as well as salivary level of SM, LB and yeast. RESULTS:
      The mean DMFT was 7.59. Females as well as the older age group of patients were
      more affected than males and younger patients. The only salivary factor showing a
      significant relationship to caries was pH. Counts of SM and LB correlated
      positively with DMFT scores. Significant higher plaque scores were present among
      the highest caries level group. CONCLUSION: The results stress the importance of
      screening for caries risk factors. The screening starts with simple clinical
      observations, expanding to a diversified pattern of tests to assess the pH level
      and SM and LB counts designed to target high-risk subjects who should be given
      the most intensive caries preventive measures.

PMID- 18335116
TI  - Caries prevalence, severity, and pattern in preschool children.
AB  - AIM: To determine caries prevalence, severity, and pattern in preschool children
      of Riyadh, Saudi Arabia. METHODS AND MATERIALS: A total of 789 randomly selected
      preschool children, 379 (48%) male and 410 (52%) female, with mean age of 4.7 (SD
      0.5) years were examined for dental caries using World Health Organization (WHO)
      diagnostic criteria. RESULTS: The overall caries prevalence among the sample was
      74.8%. The mean decayed, missing, and filled (dmft) score was 6.1 (SD 3.9) with a
      decay component of 4.66, a missing component of 0.54, and a filled component of
      0.92. There was no significant difference (p>.05) in caries prevalence and
      severity in relation to gender of the children. However, the caries prevalence
      and severity were significantly higher (p<.05) among children from government
      preschools as compared to those from private preschools. Among the posterior
      teeth, mandibular second molars (54.3%), and among anterior teeth, maxillary
      central incisors (27.9%) had the highest caries prevalence. Among the molars,
      caries prevalence was generally high in lower molars while among the anterior
      teeth, upper teeth generally had a higher caries prevalence. The majority of the
      children (50.3%) had both posterior and anterior tooth caries, 42.2% had
      posterior tooth caries only, while very few (7.5%) children had only anterior
      tooth caries. CONCLUSION: Caries prevalence and severity are very high in the
      study population, and most children have posterior tooth caries. CLINICAL
      SIGNIFICANCE: Early measures such as fissure sealants, topical fluoride
      applications (as early as safely possible), and dietary fluoride supplements
      (where indicated) are needed to prevent caries of deciduous molars in high caries
      populations.

PMID- 18335117
TI  - Short-term evaluation of resin sealing and rebonding on amalgam microleakage: an
      SEM observation.
AB  - AIMS: The aim of this study was to evaluate the effect of two different sealing
      agents on the microleakage of Class V amalgam restorations with and without resin
      rebonding. METHODS AND MATERIALS: Sixty extracted premolars were divided into six
      groups with ten teeth in each group. Class V cavity preparations were prepared on
      the facial surfaces of each tooth with the coronal margins placed in enamel and
      apical margins in cementum (dentin). The preparations in three groups were
      treated with Copalite, Scotchbond Multi-Purpose (SBMP), and no sealing agent,
      respectively. The other three groups received the same sealing agents in
      conjunction with a rebonding process. This arrangement of specimens provided for
      a comparison of the groups with and without a rebonding procedure. Amalgam was
      used as the restorative material. Specimens were thermocycled, stained, and
      sectioned. Microleakage was graded (0-3) using a stereomicroscope at 40x
      magnification. A scanning electron microscope (SEM) was used along with a high
      resolution elemental analysis. Data were analyzed with Kruskal-Wallis, Mann
      Withney, and Wilcoxon pair wise statistical tests (alpha=.05). RESULTS: The
      bonded amalgam groups demonstrated significantly less microleakage, whereas the
      unsealed groups showed the highest microleakage (P=0.001). A significant
      difference between the mean rank of the microleakage of enamel and dentin margins
      was observed (P=0.037). Insignificant, lower microleakage was observed in groups
      receiving a rebonding procedure (P=0.085). CONCLUSION: Copalite and a multi-step
      adhesive system had a significant effect on microleakage of Class V amalgam
      restorations. The influence of the multi-step adhesive system was significantly
      greater than Copalite. The rebonding of the amalgam restorations did not have a
      significant effect on microleakage.

PMID- 18335118
TI  - The effect of topical application of pure honey on radiation-induced mucositis: a
      randomized clinical trial.
AB  - AIM: Radiation-induced mucositis is an early effect of head and neck
      radiotherapy. Mucositis can cause ulcers, and patients may experience pain and
      dysphasia which need treatment. The aim of this study is to evaluate the effect
      of pure natural honey on radiation induced mucositis. METHODS AND MATERIALS: In
      this randomized single blind (examiner blind) clinical trial 40 patients with
      head and neck cancer requiring radiation to the oropharyngeal mucosa were
      randomly assigned to two groups. Twenty patients assigned to the study group
      received honey, while both the study and control groups received standard head
      and neck radiation therapy based on a standard protocol. In the study group
      patients were instructed to take 20 ml of honey 15 minutes before radiation
      therapy, then again at intervals of 15 minutes and six hours after radiation. In
      the control group patients were instructed to rinse with 20 ml of saline before
      and after radiation. Patients were evaluated weekly for progression of mucositis
      using the Oral Mucositis Assessing Scale (OMAS). Data were analyzed using the
      independent t-test, Mann-Whitney, and Friedman tests. RESULTS: A significant
      reduction in mucositis among honey-received patients compared with controls
      (p=0.000) occurred. CONCLUSION: Within the limits of this study the results
      showed the application of natural honey is effective in managing radiation
      induced mucositis. CLINICAL SIGNIFICANCE: Natural honey is a product with rich
      nutritional qualities that could be a pleasant, simple, and economic modality for
      the management of radiation mucositis.

PMID- 18335119
TI  - Arthroscopy vs. open-joint surgery for the management of internal derangement of
      the temporomandibular joint: a retrospective study comparing female subjects from
      two centers.
AB  - AIM: The aim of this retrospective study was to assess the treatment outcome of
      arthroscopy and open-joint surgery in the management of internal derangement of
      the temporomandibular joint (TMJ). BACKGROUND: Apart from pain being the major
      complaint in patients with temporomandibular joint disorders (TMDs), a variety of
      function-related symptoms are reported including joint noises, locking, limited
      movement, and alterations in occlusion. Surgical management procedures of
      internal derangement of the TMJ vary widely at present. The criteria for the
      assessment of successful outcome of the treatment are also variable. METHODS AND
      MATERIALS: The retrospective study was carried out at two centers in Paris and
      Beirut. Sixty-two female patients with an age range of 35.1 years (28 had
      arthroscopy and 34 had open surgery) were included in the study. The patients
      were followed-up for 12 months. A standardized questionnaire and visual analogue
      scale (VAS) was developed and used for the assessment of pain and mandibular
      range of motion. A chi-square test was used to observe the significance of
      difference among both groups. CONCLUSION: Within the limitations of this study,
      it was concluded arthroscopic surgery appeared to be safe with pain reduction and
      increased mandibular range of motion for 80% of the patients. Further research is
      needed on a larger prospective sample to assess the comparison of both techniques
      in terms of enhanced quality of life among the study population. CLINICAL
      SIGNIFICANCE: Arthroscopic surgery appears to be a safe, minimally invasive, and
      effective method for treating internal derangements of the TMJ.

PMID- 18335120
TI  - Staining potential of calcium hydroxide and monochlorophenol following removal of
      AH26 root canal sealer.
AB  - AIM: The focus of this study was to examine the staining potential of calcium
      hydroxide (Ca(OH)2) on tooth structure following the removal of AH26 root canal
      sealer. METHODS AND MATERIALS: Fifty maxillary anterior teeth were prepared and
      obturated with AH26 and gutta percha. The sealers were then removed 24 hours
      later and the teeth were randomly divided into two groups. Ca(OH)2 was then
      placed in the root canals of the first group of teeth as a medicament and
      camphorated monochlorophenol (CMCP) was placed in the second group of teeth after
      the filling material was removed. The color of the external tooth surfaces was
      determined before tooth preparation and two weeks after the placement of the
      medicaments. The Z test was used for statistical analysis. RESULTS: All
      experimental teeth showed varying degrees of coronal discoloration with the
      Ca(OH)2 group showing more discoloration than the CMCP group (p<0.05).
      CONCLUSION: Using Ca(OH)2 as a medicament after removing AH26 caused progressive
      discoloration of the teeth, whereas using CMCP caused only slight discoloration.
      CLINICAL SIGNIFICANCE: To avoid staining of the treated tooth, AH26 root canal
      sealer must be completely removed from the dentin walls before using a
      medicament.

PMID- 18335121
TI  - Dental age assessment of 8.5 to 17 Year-old Saudi children using Demirjian's
      method.
AB  - AIM: The aim of this study was to assess the dental age in Saudi children aged
      8.5 to 17 years using the Demirjian method. METHODS AND MATERIALS: Four hundred
      ninety panoramic radiographs of boys and girls were reviewed retrospectively. All
      children were placed in the age group closest to their chronological age. The
      dental age was scored on all seven left mandibular teeth by one examiner.
      RESULTS: Both boys and girls in age groups nine to 14 years showed advanced
      dental age compared to their chronological age which was found to be
      statistically significant except in age groups nine and 13 years. Saudi boys were
      0.3 years and Saudi girls 0.4 years ahead, on average, of French-Canadian
      children as analyzed by the Demirjian method. CONCLUSION: The standard values for
      French-Canadian children provided by Demirjian vary slightly for application to
      Saudi children. As a result, new graphs and tables were produced to convert these
      maturity scores, calculated by the Demirjian method, to the dental age for Saudi
      children.

PMID- 18335122
TI  - Saliva composition and functions: a comprehensive review.
AB  - AIM: The aim of this study was to perform a literature review about the
      composition and functions of saliva as well as describe the factors that
      influence salivary flow (SF) and its biochemical composition. BACKGROUND: Saliva
      represents an increasingly useful auxiliary means of diagnosis. Sialometry and
      sialochemistry are used to diagnose systemic illnesses, monitoring general
      health, and as an indicator of risk for diseases creating a close relation
      between oral and systemic health. REVIEW: This review provides fundamental
      information about the salivary system in terms of normal values for SF and
      composition and a comprehensive review of the factors that affect this important
      system. CONCLUSION: Since several factors can influence salivary secretion and
      composition, a strictly standardized collection must be made so the above
      mentioned exams are able to reflect the real functioning of the salivary glands
      and serve as efficient means for monitoring health. CLINICAL SIGNIFICANCE: Since
      many oral and systemic conditions manifest themselves as changes in the flow and
      composition of saliva the dental practitioner is advised to remain up-to-date
      with the current literature on the subject.

PMID- 18335123
TI  - Increase in utilization of dental sealants.
AB  - AIM: The purpose of this review is to explore how to increase utilization of
      dental sealants to reach the national 50% sealant objective as stated in the
      Healthy People 2010 document. BACKGROUND: Dental decay is the most common chronic
      childhood disease. A simple, cost-effective preventive measure to manage this
      disease is through sealant application. REVIEW: Although dental sealants are
      effective in reducing the risk of having dental decay, their rate of utilization
      among children and adolescents is below the objective set forth by the Healthy
      People 2010 document. This is related to the lack of public awareness, patient
      education, and inadequate reimbursement for sealants served by third-party
      insurers. CONCLUSION: Dental decay is the most common chronic childhood disease.
      Dental sealants are a simple, cost-effective preventive measure to manage this
      disease. In order to meet the national 50% sealant objective of the Healthy
      People 2010 document, public awareness and the education of consumers about the
      benefit of having dental sealants must be improved. Third-party insurers must
      improve the benefits for subscribers seeking dental sealant services. Using these
      approaches, the utilization of dental sealants will improve the oral health among
      the next generation of Americans.

PMID- 18335124
TI  - Review of over-the-counter treatments for aphthous ulceration and results from
      use of a dissolving oral patch containing glycyrrhiza complex herbal extract.
AB  - AIM: The aim of this article is to present a review of over-the-counter (OTC)
      treatment strategies used for aphthous ulcerations and to provide results from
      the use of an herbal extract containing glycyrrhiza. BACKGROUND: Aphthous
      ulceration, a disease of the intra-oral mucosa, is a common condition of unknown
      etiology that is often self-managed by OTC (no prescription required) medication.
      REVIEW: Preparations currently on the market can be divided into several
      categories: local anesthetic agents, oxygenating agents, mouth rinses, and
      barriers - further subdivided into paste coverings such as gels or dissolvable or
      non-dissolvable adhesive patches containing plant extract or synthetic drugs.
      Other strategies include herbs, hematinic replacement, or off-label OTC drug
      applications. While many OTC treatments are available and accepted for use with
      aphthous ulceration, a review of the literature via a number of published
      research search engines suggests that to date there are no randomized controlled
      studies to demonstrate OTC preparations do more than manage symptoms. Exceptions
      include OTC cyanoacrylate products and CankerMelts GX patches which include
      glycyrrhiza (licorice) extract. The use of CankerMelts has been shown to alter
      the course of the condition by reducing lesion duration, size, and pain. SUMMARY:
      The results of the studies reviewed here suggest CankerMelts GX discs may be as
      effective as amlexanox (which must be prescribed) in reducing pain and speeding
      healing. In addition it can be applied by the patient without the adverse events
      associated with cyanoacrylate formulations.

PMID- 18335125
TI  - Human histologic evaluation of a six-year-old threaded implant retrieved from a
      subject with osteoporosis.
AB  - AIM: The aim of this case report was to present the evaluation of the bone-to
      implant contact in an implant retrieved from a subject with osteoporosis after
      six years of load. BACKGROUND: Systemic conditions associated with osteoporosis
      have been postulated to contribute to the severity of alveolar bone loss. The
      increase in human life expectancy, the increased number of elderly subjects who
      are partially or totally edentulous, and the use of dental implants for oral
      habilitation in subjects with osteoporosis has raised several questions. REPORT:
      A 68-year-old woman with postmenopausal osteoporosis received a prosthetic
      evaluation of an implant-supported restoration. Histologically, the peri-implant
      bone appeared healthy. The peri-implant bone appeared in close contact with the
      implant surface, whereas marrow spaces could be detected in other areas along
      with prominently stained cement lines. The mean of bone-to-implant contact was
      62.51+1.96. CONCLUSION: The results of the evaluation of the dental implant
      reported here suggest the presence of osteoporosis may not be a contra-indication
      for implant placement at least after osseointegration has already been
      established.

PMID- 18335126
TI  - Treatment of painful post-traumatic peripheral neuropathy with capsaicin in an
      edentulous patient with extreme resorption in the mental region: a case report.
AB  - AIM: The aim of this report is to present a clinical case of extensive alveolar
      resorption in the mental region of the mandible of a complete denture wearer for
      which capsaicin was used for alleviation and remission of post-traumatic painful
      peripheral neuropathy. BACKGROUND: Resorption of the residual ridge occurs in a
      chronic and progressive manner, altering the configuration of the ridge and the
      mucosa covering it and subsequently compromising the stability of the complete
      denture prosthesis. Individual variability associated with such factors as
      gender, age, edentulous period, nutrition, excessive load and compression on the
      ridge, parafunctional habits, occlusal instability, and maladaptation of the
      prosthesis may have a role in the rate and manner of bone loss. REPORT: A 62-year
      old woman, edentulous at the age of 30, presented with complaints of pain and
      spontaneous "electrical shocks" in the mucosa under her mandibular complete
      denture. The pain increased while chewing approximately two years ago due to the
      pressure of this denture on her supporting tissues. The patient indicated the
      level of pain corresponded to a score of ten out of ten on the Visual Analogical
      Scale (VAS). Treatment included denture replacement and topical application of
      capsaicin gel using a custom tray technique. SUMMARY: The review of the
      literature and the results obtained from the management of this case have served
      to emphasize how much neuropathic pain research has demonstrated the complexity
      of its neurophysiologic mechanism due to the lack of association with any somatic
      manifestation. During the fabrication of a new lower denture the topical
      application of capsaicin was shown to be effective in the relief and remission of
      the painful symptoms of the neuropathy as of this writing.

PMID- 18335127
TI  - Recurrent Trichosporon asahii glossitis: a case report.
AB  - AIM: This case report aims at describing an infection of the tongue as a
      manifestation of a Trichosporon asahii infection, its association with bronchial
      asthma and steroid administration, and to present a review of the literature
      pertaining to its antifungal susceptibility profile. BACKGROUND: Trichosporon
      asahii has been reported to be associated with a wide spectrum of clinical
      manifestations, ranging from superficial infection to severe disseminated
      diseases, particularly in immunocompromised patients. CASE REPORT: A 36-year-old
      male asthmatic patient with recurrent glossitis presented with a chief complaint
      of burning sensation and two red areas on the dorsum of the tongue of three
      months duration. The glossitis was associated with Trichosporon asahii, which had
      a reduced susceptibility to some azole antifungal agents. SUMMARY: Trichosporon
      asahii is an emerging fungal pathogen which may cause a wide range of clinical
      manifestations. More reports on its various clinical presentations in the oral
      environment need to be made available in the literature. To date there is a
      paucity of data on its prevalence, pathogenesis, and antifungal resistance
      mechanism.

PMID- 18335128
TI  - Treatment of a patient with oligodontia: a case report.
AB  - AIM: The aim of this report is to describe the management of a 16-year-old
      patient with oligodontia including six permanent teeth. BACKGROUND: Oligodontia
      is agenesis of six teeth or more, excluding third molars. The etiology of
      congenital absence of teeth is believed to be involved in heredity or
      developmental anomalies. It can be isolated or as part of a syndrome. There are a
      number of options available to restore space generated by missing teeth. Dental
      treatment can vary depending on the severity of the disease and generally
      requires a multidisciplinary approach. Treatment options include orthodontic
      therapy, implants, adhesive techniques, and removable prostheses. REPORT: A 16
      year-old male patient with oligodontia affecting six permanent teeth received
      conservative care that met his and his parent's expectations. The existing
      primary teeth were restored to resemble permanent teeth in order to achieve a
      favorable esthetic result using direct composite resin. The restorative treatment
      was provided for the psychosocial comfort of the young patient. The loss of teeth
      in young patients can cause esthetic, functional, and psychological problems
      particularly if the teeth of the anterior region are involved. SUMMARY: Adhesive
      techniques and new restorative materials represent current options in the
      management of the dental rehabilitation of young patients with oligodontia.

PMID- 18335129
TI  - Treatment considerations for a patient with hypohidrotic ectodermal dysplasia: a
      case report.
AB  - AIM: This clinical report describes the oral rehabilitation of a 6-year-old male
      ectodermal dysplasia (ED) patient diagnosed with hypodontia. BACKGROUND: ED is a
      hereditary disease characterized by a congenital dysplasia of one or more
      ectodermal structures and their accessory appendages. Common manifestations
      include defective hair follicles and eyebrows, frontal bossing with prominent
      supraorbital ridges, nasal bridge depression, and protuberant lips. Intraorally,
      most common findings are anadontia or hypodontia, conical teeth, and generalize
      spaces. The patient may suffer from dry skin, hyperthermia, and unexplained high
      fever as a result of deficiency of sweat glands. REPORT: A six-year-old boy who
      exhibited many of the manifestations of ED as well as behavioral problems and a
      severe gag reflex. The treatment was designed to improve his appearance and oral
      functions and included the fabrication of several removable prostheses and acid
      etched composite resin restorations during his growth and development. SUMMARY:
      Young patients with ED need to be evaluated early by a dental professional to
      determine the oral ramifications of the condition. When indicated, appropriate
      care needs to be rendered throughout the child's growth cycle to maintain oral
      functions as well as to address the esthetic needs of the patient. This clinical
      report demonstrates that removable partial dentures associated with direct
      composite restorations can be a reversible and inexpensive method of treatment
      for young ED patients.

PMID- 18335130
TI  - Inflammatory fibrous hyperplasia treated with a modified vestibuloplasty: a case
      report.
AB  - AIM: The purpose of this report is to present a case of surgical and prosthetic
      treatment of a woman with inflammatory fibrous hyperplasia (IFH) and her
      evaluation during a six month period. BACKGROUND: IFH is a benign pathology,
      prevalent in female patients, and principally associated with ill-fitting
      prosthetic devices in need of adjustment. It is common for patients to require
      surgical removal of the hyperplastic tissue and fabrication of a new prosthesis.
      CASE REPORT: A 55-year-old female with a history of smoking presented with a
      chief complaint of missing the scheduled adjustment of her maxillary complete
      denture and the presence of moveable tissue under the denture. Surgical excision
      of the hyperplastic tissue followed with fixation of the prosthesis for six
      months to guide the healing of the soft tissue and to reshape the contours of the
      maxillary supporting tissues. SUMMARY: Surgical removal of hyperplasic soft
      tissue is a routine procedure, and the fixation of the prosthesis for the support
      of tissue during healing improves intraoral conditions for the fabrication of a
      new prosthesis in the future.

PMID- 18335131
TI  - Regional odontodysplasia: report of a case in the mandible crossing the midline.
AB  - AIM: This report presents an unusual case of regional odontodysplasia (RO) in the
      mandible which crosses the midline along with its clinical management.
      BACKGROUND: RO is an uncommon, nonhereditary unilateral developmental anomaly
      involving the dental hard tissues, most frequently affecting the maxillary teeth.
      REPORT: RO was diagnosed in a 12-year-old. The dysplastic teeth were the
      mandibular canines, lateral incisors, central incisors, and the right premolars.
      The treatment was extraction of the affected teeth followed by provisory
      prosthetic rehabilitation. SUMMARY: The etiology of RO remains obscure. In this
      case a possible association with pre-natal trauma is suspected. The literature is
      not unanimous as to the management of RO. Nevertheless, the presence of a dental
      abscess is an indication for extraction. Since general bone quality is not
      affected, a provisory prosthesis was fabricated as the patient waits for future
      implant rehabilitation. The executed treatment met the expectations of the
      patient and her mother as it improved the patient's masticatory function,
      esthetics, and quality of life. CLINICAL SIGNIFICANCE: The general practitioner
      must be prepared to deal with different situations in the dental office. The
      diagnosis of RO relies mainly on clinical and radiographic findings, and its
      treatment depends on the affected teeth, the severity of the dysplasia, the
      presence of infection, and the patient's age.

PMID- 18335132
TI  - AAOMP case challenge: a mass of the tuberosity.
AB  - A 72-year-old male presented with a raised lesion in the area of the maxillary
      right tuberosity. The patient had become aware of the lesion only recently when
      his upper complete denture would not seat properly.

PMID- 18335133
TI  - Towards the rational design of platinum(II) and gold(III) complexes as antitumour
      agents.
AB  - Metal complexes afford an opportunity for the discovery of new antitumour drugs
      with truly novel mechanisms of action. Various tactics and some new concepts have
      been employed to improve the physico-chemical and biological properties of metal
      complexes. Recent advances in this area demonstrate a bright prospect for the
      utilization of metal complexes in cancer chemotherapy. The theme of this article
      focuses on the approaches towards the rational design of platinum(II) and
      gold(III) complexes with antitumour properties based on the updated understanding
      of the mechanism of action of these compounds. The complexes summarized in this
      work include monofunctional platinum(II) complexes, multinuclear platinum(II)
      complexes, hybrid and targeted platinum(II) complexes, and gold(III) complexes.
      Most of them violate the established structure-activity relationships and
      demonstrate different reactivities from cisplatin and thereby show some potential
      for the prevention of detoxification.

PMID- 18335134
TI  - Nanofabrication with metal containing dendrimers.
AB  - Dendrimers are versatile building blocks for "bottom-up" nanofabrication because
      they combine molecular structure and nanoscale dimensions. Moreover, dendrimers
      can be functionalized at their numerous peripheral end groups, in their core,
      along their branches, and in the voids of their interior. This Frontier
      highlights the potential of metal containing dendrimers for nanofabrication.

PMID- 18335135
TI  - Immobilization of a hexaphyrin(1.0.1.0.0.0) derivative onto a tentagel-amino
      resin and its use in uranyl cation detection.
AB  - The synthesis of an isoamethyrin derivative containing two CH(2)CH(2)CO(2)CH(3)
      moieties in the beta-pyrrolic positions and its use in the colorimetric detection
      of the uranyl cation after immobilization onto a solid support is reported.

PMID- 18335136
TI  - Excitation energy flow control in {Ru(2,2'-bipyridine)2}-{pyridylporphyrin}2
      systems.
AB  - The direction of excitation energy migration is reversed in a system composed of
      {Ru(bpy)(2)}-{pyridylporphyrin}(2) by the addition of a Zn(2+) ion. The Zn(2+)
      system shows an excitation-wavelength dependent emission.

PMID- 18335137
TI  - Coordination molecular hats binding acetonitrile via C-H...pi interactions.
AB  - The [M(3)L(3)](3+) metallo-macrocycles with syn, syn, syn conformation, self
      assembled from crown ether functionalized 1,10-phenanthroline Pd(II) nitrates
      with naphthanoimidazole, bind a solvent CH(3)CN within the naphthanoimidazolate
      built cavity through C-H...pi interactions in the crystalline state.

PMID- 18335138
TI  - An unusual trigonal D3 assembly composed of molybdate anions and multiply bonded
      dimolybdenum units.
AB  - Oxidation of the molybdate-linked pair having two quadruply bonded Mo(2)(4+)
      units, [Mo(2)(DAniF)(3)](2)(micro(2)-MoO(4)), (DAniF = N,N'-di-(p
      anisyl)formamidinate) leads to the formation of a species consisting of three
      oxidized Mo(2)(5+) units connected by two micro(3)-MoO(4)(2-) dianions,
      {[Mo(2)(DAniF)(3)](3)(micro(3)-MoO(4))(2)}(2+). This cation displays overall D(3)
      point group symmetry due to a slight twisting of the three Mo(2)(5+) units about
      the threefold symmetry axis. This distortion removes all mirror symmetry but
      preserves all C(2) axes orthogonal to the unique C(3) axis. Cyclic voltammetry of
      {[Mo(2)(DAniF)(3)](3)(micro(3)-MoO(4))(2)}(2+) in CH(2)Cl(2) reveals three
      reversible one-electron redox processes, corresponding to successive reduction of
      each of the three Mo(2)(5+) units, with DeltaE(1/2) separations of 0.36 V and
      0.41 V.

PMID- 18335139
TI  - Borane reaction chemistry. Alkyne insertion reactions into boron-containing
      clusters. Products from the thermolysis of [6,9-(2-HC[triple bond]C-C5H4N)2
      arachno-B10H12].
AB  - The stirring of [ortho-(HC[triple bond]C)-C(5)H(4)N] with [nido-B(10)H(14)] in
      benzene affords [6,9-{ortho-(HC[triple bond]C)-C(5)H(4)N}(2)-arachno-B(10)H(12)]
      1 in 93% yield. In the solid state, 1 has an extended complex three-dimensional
      structure involving intramolecular dihydrogen bonding, which accounts for its low
      solubility. Thermolysis of 1 gives the known [1-(ortho-C(5)H(4)N)-1,2-closo
      C(2)B(10)H(11)] 2 (13%), together with new [micro-5(N),6(C)-(NC(5)H(4)-ortho
      CH(2))-nido-6-CB(9)H(10)] 3 (0.4%), [micro-7(C),8(N)-(NC(5)H(4)-ortho-CH(2))-nido
      7-CB(10)H(11)] (0.4%) , 4 binuclear [endo-6'-(closo-1,2-C(2)B(10)H(10))-micro
      (1(C),exo-6'(N))-(ortho-C(5)H(4)N)-micro-(exo-8'(C),exo-9'(N))-(ortho
      (CH(2)CH(2))-C(5)H(4)N)-arachno-B(10)H(10)] (0.5%) 5, and [exo-6(C)-endo-6(N)
      (ortho-(CH[double bond]CH)-C(5)H(4)N)-exo-9(N)-(ortho-(HC[triple bond]C)
      C(5)H(4)N)-arachno-B(10)H(11)] 6. An improved solvent-free route to 2 is also
      presented. This set of compounds features an increasing cluster incorporation of
      the ethynyl moiety, initially by an effective internal hydroboration, affording
      an arachno to nido and then a nido to arachno:closo sequence of cluster geometry.
      An alternative low-temperature route to internal hydroboration is demonstrated in
      the room temperature reaction of [closo-B(11)H(11)][N(n)Bu(4)](2) with CF(3)COOH
      and [ortho-(HC[triple bond]C)-C(5)H(4)N], which gives [micro-1(C),2(B)-[ortho
      C(5)H(4)N-CH(2)]-closo-1-CB(11)H(10)] 7 (40%) in which one carbon atom is
      incorporated into the cluster; a similar reaction with [ortho-(N[triple bond]C)
      C(5)H(4)N] affords [N(n)Bu(4)][7-(ortho-N[triple bond]C-C(5)H(4)N)-nido
      B(11)H(12)], 8 (68%) and stirring [ortho-(N[triple bond]C)-C(5)H(4)N] with [nido
      B(10)H(14)] quantitatively affords the cyano analogue of 1, [6,9-{ortho-(N[triple
      bond]C)-C(5)H(4)N}(2)-arachno-B(10)H(12)] 9. All compounds were characterised by
      single-crystal X-ray diffraction analysis and NMR spectroscopy.

PMID- 18335140
TI  - Synthesis of nickel complexes with bidentate N,O-type ligands and application in
      the catalytic oligomerization of ethylene.
AB  - The dinuclear complexes [Ni(micro-Cl){(4,5-dihydro-4,4-dimethyloxazol-2
      yl)methanol}](2)Cl(2) and [Ni(micro-Cl){(pyridin-2-yl)methanol}](2)Cl(2) 16 have
      been synthesized in high yields by reaction of NiCl(2) with 2 mol. equiv. of the
      ligands 4,5-dihydro-4,4-dimethyloxazol-2-yl)methanol 13 or (pyridin-2-yl)methanol
      15, respectively. The reaction of NiCl(2) with 3 mol. equiv. of 15 afforded in
      high yield the mononuclear, octahedral mer-[Ni{(pyridin-2-yl)methanol}(3)Cl(2)]
      complex 18. The reaction of 16 with NaH led to the deprotonation of one of the
      pyridine alcohol ligands to form [Ni{(pyridin-2-yl)methanol}{(pyridin-2
      yl)methanolate}Cl] 21 in which the metal is coordinated by one pyridine alcohol
      and one pyridine alcoholate ligand. The crystal structures of the dinuclear,
      chloride-bridged octahedral complexes in 14.C(6)H(12) and in 16.3CH(2)Cl(2) and
      of the mononuclear, octahedral complex 18 in 18.CH(2)Cl(2) have been determined
      by X-ray diffraction. In the latter case, intermolecular OH...Cl bonding
      interactions generate a centrosymmetric pseudo-dimer. Complexes 14, 16, and 21
      have been tested in ethylene oligomerization with AlEtCl(2) (Al/Ni ratios of 2, 4
      or 6) or MAO (50, 100 or 200 equiv.) as co-catalysts under 10 bar of ethylene and
      yielded mostly dimers and trimers. Complex 16 in the presence of 6 equiv. of
      AlEtCl(2) proved to be the most active system with a turnover frequency (TOF) up
      to 187 500 C(2)H(4) (mol Ni h)(-1). Complex 16 with 200 equiv. of MAO was also
      the most active, with TOF up to 104 300 C(2)H(4) (mol Ni h)(-1) under 30 bar of
      ethylene.

PMID- 18335141
TI  - Synthesis and structural variations of substituted phenylamide complexes of the
      heavy alkaline earth metals calcium, strontium and barium.
AB  - Starting material KN(H)C(6)H(3)-2,6-F(2) was prepared via a transamination
      reaction from KNH(2) and 2,6-F(2)C(6)H(3)NH(2) in THF and crystallized from 1,4
      dioxane (diox) as the three-dimensional polymer [(diox)(1.5)K{N(H)-2,6
      F(2)C(6)H(3)}.diox(0.5)](infinity) (1). The metathesis reaction of (THF)(4)CaI(2)
      with KN(Me)Ph in THF yields monomeric (THF)(4)Ca[N(Me)Ph](2) (2) with a nearly
      linear N-Ca-N moiety of 179.84(8) degrees . The metathesis reaction of
      (THF)(4)CaI(2) with KN(H)Mes yields trinuclear (THF)(6)Ca(3)[N(H)Mes](6) (3) with
      a linear Ca(3) fragment and bridging 2,4,6-trimethylphenylamido groups. The
      reaction of 1 with (THF)(4)CaI(2) gives dinuclear (THF)(5)Ca(2)[N(H)-2,6
      F(2)C(6)H(3)](4).2THF (4) with three bridging and one terminally bound 2,6
      difluorophenylamide. A similar reaction of (THF)(5)SrI(2) with KN(H)-2,6
      F(2)C(6)H(3) yields dinuclear (THF)(6)Sr(2)[N(H)-2,6-F(2)C(6)H(3)](3)I.THF (5) in
      which the iodide anion binds terminally. This iodide ligand cannot be substituted
      as easily by excess KN(H)-2,6-F(2)C(6)H(3). The metathesis reaction of
      (THF)(5)BaI(2) with KN(H)-2,6-F(2)C(6)H(3) leads to the formation of
      [(THF)(2)Ba{N(H)-2,6-F(2)C(6)H(3)}(2)](infinity) (6) which crystallizes as a one
      dimensional polymer with bridging 2,6-difluorophenylamide anions and additional
      Ba-F-bonds.

PMID- 18335142
TI  - Synthesis, crystal structures and magnetic properties of tricyanomethanide
      containing copper(II) complexes.
AB  - The preparation, crystal structures and magnetic properties of the copper(II)
      complexes of formula [Cu(pyim)(tcm)(2)](n) (1), [Cu(bpy)(tcm)(2)](n) (2),
      [Cu(4)(bpz)(4)(tcm)(8)] (3), {[Cu(terpy)(tcm)].tcm}(n) (4) and
      {[Cu(2)(tppz)(tcm)(4)].3/2H(2)O}(n) (5) [pyim = 2-(2-pyridyl)imidazole, tcm =
      tricyanomethanide, bpy = 2,2'-bipyridine, bpz = 2,2'-bipyrazine, terpy =
      2,2':6',2''-terpyridine and tppz = 2,3,5,6-tetrakis(2-pyridyl)pyrazine] are
      reported. Complexes, 1, 2 and 4 are uniform copper(II) chains with single- (1 and
      4) and double-(2) micro-1,5-tcm bridges with values of the intrachain copper
      copper separation of 7.489(1) (1), 7.520(1) and 7.758(1) (2) and 7.469(1) A (4).
      Each copper atom in 1, 2 and 4 is five-coordinate with bidentate pyim (1)/bpy (2)
      and tridentate terpy (4) ligands and nitrile-nitrogen atoms from bridging (1,2
      and 4) and terminal (1) tcm groups building a distorted square pyramidal
      surrounding. The structure of 3 is made up of neutral centrosymmetric rectangles
      of (2,2'-bipyrazine)copper(II) units at the corners, the edges being built by
      single- and double-micro-1,5-tcm bridges with copper-copper separations of
      7.969(1) and 7.270(1) A, respectively. Five- and six-coordinated copper atoms
      with distorted square pyramidal and elongated octahedral environments occur in .
      Compound 5 is a neutral copper(II) chain with regular alternating bis-tridentate
      tppz and double micro-1,5-tcm bridges, the intrachain copper-copper distances
      being 6.549(7) and 7.668(1) A, respectively. The two crystallographically
      independent copper atoms in 5 have an elongated octahedral geometry with three
      tppz nitrogen atoms and a nitrile-nitrogen atom from a bridging tcm group in the
      equatorial positions, and two nitrile nitrogen atoms from a terminal and a
      bridging tcm ligand occupying the axial sites. The investigation of the magnetic
      properies of 1-5 in the temperature range 1.9-295 K has shown the occurrence of
      weak ferro- [J = +0.11(1) cm(-1) (2)] and antiferromagnetic interactions [J = 
      0.093(1) (1), -0.083(1) (4), -0.04(1) and 1.21(1) cm(-1) (3)] across the micro
      1,5-tcm bridges and intermediate antiferromagnetic coupling [-J = 37.4(1) cm(-1)
      (5)] through bis-tridentate tppz. The values of the magnetic interactions are
      analyzed through simple orbital symmetry considerations and compared with those
      previously reported for related systems.

PMID- 18335143
TI  - Structural chemistry of (PPh4)2M(WS4)2 materials.
AB  - In this paper we discuss the structural chemistry of (PPh(4))(2)M(WS(4))(2) (M =
      Co, Ni, Zn) materials. For M = Ni we and others have been unable to grow single
      crystals and we report the structure determination from powder diffraction. The
      material is triclinic (P1, a = 9.3730(2), b = 12.4951(3), c = 12.5189(3) A, alpha
      = 65.814(1), beta = 83.751(1), gamma = 69.571(1) degrees at T = 293 K). It
      contains square-planar coordination around Ni. For M = Zn we have isolated two
      polymorphs. We describe new analysis of the complex superstructure and diffuse
      scattering observed in the tetragonal polymorph (I4, a = 18.723(4), c = 13.563(4)
      A at T = 120 K) and the bulk preparation of a monoclinic (P2(1)/c, a =
      18.6397(4), b = 15.3693(5), c = 18.9822(5) A, beta = 109.239(2) degrees at T =
      293 K) polymorph isostructural with the M = Co material.

PMID- 18335144
TI  - Porphyrin complexes containing coordinated BOB groups: synthesis, chemical
      reactivity and the structure of [BOB(tpClpp)]2+.
AB  - The reactions of boron halides with free base porphyrins under conditions where
      partial hydrolysis of the boron halides can occur give diboron porphyrin
      complexes containing BOB moieties in which each boron is bonded to two porphyrin
      nitrogen atoms. BF(3).OEt(2) with H(2)(por) gives B(2)OF(2)(por) (por = tpp, ttp,
      tpClpp, oep) which has an asymmetric structure in which one boron lies in the
      porphyrin plane (B(ip)) while the other lies above it (B(oop)). BCl(3).MeCN with
      H(2)(por) gives B(2)O(2)(BCl(3))(2)(por) which contains a four-membered B(2)O(2)
      ring and is stable only in the presence of excess BCl(3). BBr(3) with
      Li(2)(tpClpp) gives the dicationic complex [B(2)O(tpClpp)](2+) as its [BBr(4)](-)
      salt, and is the first example of a boron porphyrin containing three-coordinate
      boron to be structurally characterised. B(2)O(2)(BCl(3))(2)(por) can be
      chromatographed on basic alumina to give the hydroxyboron complex
      B(2)O(OH)(2)(por), which is deduced from its NMR spectra and DFT calculations to
      have a structure analogous to B(2)OF(2)(por). The OH protons are shifted upfield
      to near delta -4 (B(oop)-OH) and -10 (B(ip)-OH) by the diamagnetic porphyrin ring
      current. The reaction of either B(2)O(2)(BCl(3))(2)(por) or B(2)O(OH)(2)(por)
      (por = ttp, tpClpp) with alcohols (ROH, R = Et, 4-C(6)H(4)CH(3)) gives
      B(2)O(OR)(2)(por), which can in turn be converted to B(2)O(OR)(OH)(por) by
      repeated chromatography. The reaction of PhBCl(2) with H(2)(por) (por = ttp,
      tpClpp) gives B(2)O(Ph)(OH)(por) which has been characterised by spectroscopy in
      concert with DFT calculations. It is a further example of the B(2)OF(2)(por)
      structural type, in which the phenyl group is coordinated to the out-of-plane
      boron and the OH group to the in-plane boron, as are its derivatives
      B(2)O(Ph)(X)(tpClpp) (X = F, OEt). Steric drivers for the facile hydrolysis of
      haloboron porphyrins relative to their dipyrromethene and expanded porphyrin
      counterparts are discussed.

PMID- 18335145
TI  - Amidinate-carboxylate complexes of dimolybdenum and ditungsten:
      M2(O2CR)2((NiPr)2CR')2. Preparations, molecular and electronic structures and
      reactions.
AB  - The compounds M(2)(O(2)CMe)(4) and the lithium amidinates Li[(N(i)Pr)(2)CR] react
      to give the new compounds trans-M(2)(O(2)CMe)(2)[(N(i)Pr)(2)CR](2) where M = Mo
      or W and R = Me (M = Mo only), -C[triple bond]C(t)Bu, -C[triple bond]CPh and 
      C[triple bond]C-Fc where Fc = 1-ferrocenyl. The limitations of this type of
      reaction are described based on steric considerations together with the
      preparation and characterization of the compound Mo(2)(micro-O(2)C-9
      anthracene)(2)[eta(2)-(N(i)Pr)(2)CMe](2). The electronic structures of the bis
      amidinate-bis-carboxylate M(2) complexes are described based on model compounds
      employing density functional theory and are correlated with the experimental
      observations of their physicochemical properties and in particular their observed
      electronic absorption spectra which show intense MLCT absorption bands.
      Preliminary studies of the reactions of these bis-amidinate-bis-carboxylate
      complexes in the preparation of 1-D oligomers are also described along with the
      preparation and molecular structures of the compounds [Li(N(i)Pr)(2)CR.THF](2)
      where R = 2-thienyl or -C[triple bond]C-Ph. The kinetic lability of these new
      M(2)-containing compounds toward ligand exchange is also noted.

PMID- 18335146
TI  - Macropolyhedral boron-containing cluster chemistry. The reversible disassembly
      and reassembly of the hexagonal pyramidal {B7} feature in the [S2B18H19]- anion.
AB  - The [S(2)B(18)H(19)](-) anion 1, from syn-B(18)H(22) 2 with NaH and elemental
      sulfur, has an unusual arachno-type eleven-vertex {SB(10)} subcluster that has an
      open hexagonal pyramidal {B(7)} structural feature. This is conjoined, with two
      boron atoms in common, to a second {SB(10)} subcluster of conventional nido
      eleven-vertex geometry. Protonation of 1 forms neutral [S(2)B(18)H(20)] 4.
      Subsequent deprotonation of 4 yields the fluxional [S(2)B(18)H(19)](-) anion 5,
      which is isomeric with 1. Neutral 4and anion 5 do not have the {B(7)} hexagonal
      pyramidal feature. Neutral 4 consists of conventional nido eleven-vertex {SB(10)}
      and arachno ten-vertex {SB(9)} subclusters conjoined with a single spiro boron
      atom in common. Anion 5 is closely related to 4, but with an additional inter
      boron intercluster link. Anion 5 spontaneously reverts to anion 1 over a few
      hours at room temperature, remarkable in that the open {B(7)} hexagonal pyramid
      is regenerated. DFT B3LYP/6-31G* calculations suggest definitive structures for 4
      and 5 that are substantiated by agreement between observed NMR delta((11)B)
      values and boron nuclear shielding as calculated by the GIAO approach on the DFT
      calculated structures. Extension of this approach additionally defines transition
      states and intermediates for the fluxionality of 5, and also for the reassembly
      of the starting anion 1, together with its {B(7)} feature, from fluxional 5. The
      fluxionality of 5 involves the inter-subcluster transfer of a {BH} unit. The
      reassembly of 1 from 5 involves a DSD rearrangement and two successive hydrogen
      atom hops. Confidence in the application of this method to these large
      macropolyhedral assemblies is afforded in the first instance by good agreement
      between delta((11)B)(OBS) and delta((11)B)(CALC) for the structurally
      characterised original anion 1, the only species amongst these to be
      crystallographically established.

PMID- 18335147
TI  - A new series of dinuclear Au(I) complexes linked by diethynylpyridine groups.
AB  - A series of novel digold complexes incorporating ethynyl pyridine derivatives as
      a spacer unit, [(R(3)P)Au(C[triple bond]C)X(C[triple bond]C)Au(PR(3))] (R = Ph, X
      = 2,5-pyridine (1); R = Cy (cyclohexane), X = 2,5-pyridine (2); R = Ph, X = 2,6
      pyridine (3); R = Ph, X = 2,5'-bipyridine (4); R = Ph, X = 2,6'-bipyridine (5)),
      has been synthesised. All the complexes have been characterised spectroscopically
      and the structures determined by single-crystal X-ray crystallography. The
      central (C[triple bond]C)(X)(C[triple bond]C) unit is essentially linear for
      complexes 1, 2 and 4 and kinked for complexes 3 and 5, but only in 1, with the
      shortest spacer group and the less bulky phosphine ligand, is there evidence of
      d(10)...d(10) Au...Au interactions (Au-Au 3.351(2) A). The solution UV/visible
      absorption and emission spectra for all the complexes are similar to those of the
      free ligands suggesting that the spectra are dominated by pi-pi* ligand-centred
      transitions and this is confirmed by DFT calculations.

PMID- 18335148
TI  - Transitional cell carcinoma of the upper ureter metastatic to the thoracic spine
      presenting as a spinal cord compression.
AB  - We performed a left nephroureterectomy for a gentleman with transitional cell
      carcinoma of the upper ureter. Histological analysis revealed it to be a T1
      lesion, but to be highly mitotically active. The gentleman defaulted on adjuvant
      therapy and defaulted on follow-up. He represented with symptoms of acute spinal
      cord compression and magnetic resonance imaging demonstrated a lesion at T6/7.
      Neurosurgical resection of the lesion showed it to be a metastatic deposit from
      the ureteric primary. Despite surgical debulking and subsequent radiotherapy to
      the lesion, the patient died secondary to metastatic complications. This case
      report is of interest to the surgeon as it demonstrates both the high metastatic
      potential of upper tract carcinomas and educates the surgeon on the presentation
      of acute spinal cord compression.

PMID- 18335149
TI  - Essential type II mixed cryoglobulinemia causing pyoderma gangrenosum-like
      ulcers.
AB  - A 47-year-old, otherwise healthy woman presented with multiple deep ulcers
      located primarily on her lower extremities that presented 6 days ago as blisters.
      A biopsy revealed livedoid vasculopathy, without any evidence of vasculitis.
      Extensive laboratory workup was positive only for type II cryoglobulins.

PMID- 18335150
TI  - [Chemosensitivity test on brain tumors].
AB  - During last 50 years chemotherapy has played a very important part in the cancer
      treatment. However, success or failures of news drugs in one particular cancer
      its difficult to predict. In vitro chemosensitivity is an attractive method for
      knowing about responses of a tumor to ChT treatment and assess the best dose in
      the patient with cancer. OBJECTIVE: To know brain tumors sensitivity against
      antineoplastic drugs. METHODS: Five different drugs (carmustin, camptotecin,
      taxol, hydroxyurea and tamoxifen) were tested on short-term cultures from 7
      patients with Glioblastoma multiforme, 15 patients with meningiomas and one
      patient with meduloblastoma. For testing chemosensitivity we used MTT assay, and
      we measured optic density by spectophotometry to 450 nm. RESULTS. A total of 49
      measurement were done, getting 44 valid dose-result curves. For each drug we used
      from 10-2 M to 10-12 M gap, and IC50 result was representative of tumor
      sensitivity to the drug. CONCLUSION: our data support MTT assays like valid
      method for measuring in vitro chemosensitivity in brain tumors to news drugs.

PMID- 18335151
TI  - [Surgical treatment for spontaneous intracerebral haemorrhage. Part I:
      supratentorial haematomas].
AB  - Spontaneous intracerebral haematoma (SICH) represents one the most severe
      subtypes of ictus. However, and despite a high incidence, medical treatment is
      almost limited to life support and to control intracranial hypertension and
      indications of surgical treatment are poorly defined. The aim of this paper was
      to review the evidence supporting surgical evacuation of SICH. Ten clinical
      trials and five meta-analyses studying the results of surgical treatment on this
      pathology were found on English literature. These studies considered all
      together, failed to show a significant benefit of surgical evacuation in patients
      with SICH considered as a whole. However, a subgroup of these patients has been
      considered to potentially present a better outcome after surgical treatment.
      Current recommendations on supratentorial intra-cerebral haemorrhage state that
      young patients with lobar haematomas causing deterioration on the level of
      consciousness should be operated on. Patients suffering from putaminal haematomas
      and fitting with the same criteria of age and neurological deterioration could
      also benefit from surgery, at least on terms of survival. Deep neurological
      deterioration with GCS<5, thalamic location, severe functional deterioration on
      basal condition or advanced age precluding an adequate functional outcome, have
      been traditionally considered criteria contraindicating surgery. Given the
      absence of strong scientific evidence to indicate surgery, this measure should be
      taken on a tailored manner, and taking into account the social-familiar
      environment of the patient, that will strongly condition his/her future quality
      of life.

PMID- 18335152
TI  - [Intracranial hemorrhage due to aneurysms and arteriovenous malformations during
      pregnancy and puerperium].
AB  - INTRODUCTION: Subarachnoid hemorrhage for aneurysms and arteriovenous
      malformations is most frequent during pregnancy and puerperium. We analyzed
      behavior and management of this patients and the effect on it of our Maternal
      Health Program. PATIENTS AND METHODS: There were 437 pregnancy and 717 puerperal
      complicated patients between january 1996 to december 2005, 41 maternal deaths of
      all causes and 14 indirect maternal deaths. There were operated on 454 patients
      with intracranial aneurysms and arteriovenous malformations in this period.
      Pregnant patients and fetus were evaluated to select mode of delivery. A
      specialized medical team managed precociously these patients. Vascular lesions
      were clipped by microsurgical methods. Anesthetic management considered pregnancy
      and fetal complexities. We did not use endovascular methods. Postoperative
      management was performed on intensive care unit. RESULTS: There were eight
      pregnant and puerperal patients with subarachnoid hemorrhage due to aneurysms and
      arteriovenous malformations. 2% of all patients were operated on by this cause.
      Six harboured intracranial aneurysms and two arteriovenous malformations. We
      performed seven surgical procedures, five for aneurysms and two for
      malformations. There was a delivery rate of 2.1 and seven normal newborn. Four
      patients achieved a complete neurological recovery, two a partial recovery and
      there were two deceased. This cause constituted 14% of all indirect maternal
      deaths. CONCLUSION: A precocious clinical diagnosis, neuroimaging studies and
      interdisciplinary management that involve intensive therapy, obstetric attention
      and neurovascular surgical treatment determined an increment in the diagnosis of
      these lesions that require opportune microsurgical or endovascular treatment to
      prevent maternal death and fetal damage.

PMID- 18335153
TI  - [Lumbar post-laminectomy syndrome: II. Pain management using neuro-modulation
      techniques].
AB  - The application of neuro-modulation techniques in general is currently gaining
      acceptance in various aspects of medicine. Neuro-modulation is defined as:
      "Therapeutical interventions using implantable devices to modify the functioning
      of central, peripheral and autonomic nervous systems". Following lumbar disc
      surgery, or lumbar spine surgery in general, several chronic pain syndromes can
      result, either in the lumbar region and/or in the lower limbs. The current status
      is for the application of surgery to the degenerative spine (degenerative disc
      disease and lumbar stenosis) for the relief of chronic pain. A review of the
      methodology of evidence based medicine, show that the instrumented and fusion
      techniques are not the answered despite 20 years of the use of these techniques
      following failure of surgery for the relief of back pain syndrome. Neuro
      modulation techniques represent a step in the right direction for the management
      of these chronic pain syndromes. Frequently they enable the resolution of chronic
      pain following spine surgery without having to resort to repeat surgery. We
      describe here the different neuro-modulation techniques (spinal cord stimulation,
      spinal drug infusions) which can be used in the case of back surgery failure, and
      we describe technical aspects and "tricks of the trade" for the correct
      implantation of the devices used in techniques. Neuro-modulation techniques are
      applied to the management of chronic pain following disc surgery and represent a
      valid alternative to repeat surgery and/or arthrodesis (instrumented or not).
      Neurosurgeons are again called to play active roles in the field of neuro
      modulation for the treatment.

PMID- 18335154
TI  - Can facet joint infiltrative analgesia reduce postoperative pain in degenerative
      lumbar disc surgery?
AB  - OBJECTIVE: Perioperative analgesia effects the postoperative course of pain. The
      purpose of this study was to evaluate its possible relation with the consumption
      of dolantine and analgesics and the facet-induced pain and postoperative pain
      score in degenerative disc surgery. METHODS: We employed perioperative intra- and
      perifacet bupivacaine infiltration technique to reduce the postoperative pain
      after lumbar disc surgery. The study was randomized and observer blinded
      enrolling 40 American Society of Anesthesiologists physical status class I-II
      patients scheduled for elective degenerative lumbar disc surgery. The patients
      were divided into two groups of 20 of which Group 1 underwent injection of
      bupivacaine into the subcutaneous and muscular layers around the incision site,
      while Group 2 underwent additional intra- and perifacetal joint infiltration.
      Postoperatively, the patients were provided with a programmed patient-controlled
      pump which was only activated on demand to infuse dolantine for the next 24
      hours. In the postanesthesia care unit the delay for analgesia and the dose of
      dolantine used were recorded. RESULTS: There was no statistical significance
      between these two groups regarding postoperative visual analoque scale scores.
      The time before the first analgesic request was significantly longer in facet
      group (p= 0,006). The cumulative dolantine dose was also significantly lower in
      the facet group (p= 0,001). CONCLUSION: The results indicate that facet joint
      infiltrative analgesia may have an effect on the postoperative analgesic
      requirement and reduce the dolantine consumption.

PMID- 18335155
TI  - Cavernomas in children with brain tumors: a late complication of radiotherapy.
AB  - BACKGROUND: Delayed complications of radiation therapy comprise cerebral atrophy,
      radionecrosis and induction of tumors. Recent reports indicate the possibility of
      the "de-novo" formation of intracranial cavernomas in patients submitted to
      radiation therapy to the brain. OBJECTIVES: To report three children, two with
      medulloblastomas and one with a pineal germinoma, treated with radiotherapy that
      developed intracerebral cavernous hemangiomas some years after treatment. With
      this work, we aim to draw attention to this occurrence in the neurosurgical
      community. RESULTS: The patients were two girls and one boy with ages comprised
      between 2.5 and 7 years (mean 5.2 years). The average interval from irradiation
      to the appearance of cavernoma was of 5.3 years (range 5-6 years). The lesions
      were found during the routine neuroimaging studies performed for the follow-up of
      their primary neoplasms. No patient showed signs or symptoms related to the
      cavernomas. However, the three children will need both clinical and neuroimaging
      surveillance to monitor the evolution of these incidentally discovered lesions.
      CONCLUSIONS: Intracranial cavernomas can occur years after cerebral radiation
      therapy. In spite of previous reports that show a high incidence of bleeding
      lesions, cavernomas may be found incidentally during the neuroimaging
      surveillance studies that are performed to children with brain tumors previously
      treated with radiotherapy. In these cases, a conservative attitude seems to be
      advisable, reserving surgery only for those lesions that grow or bleed.

PMID- 18335156
TI  - Bilateral frontal epidural abscess.
AB  - DESCRIPTION: A 19-year-old male with periorbital painful swelling, headache and
      vomiting was admitted to our clinic. Because of the diagnosis of sinusitis he had
      received medical treatment in another center two months before, consisting of
      antibiotics and analgesics. However as a result of valid persistence of the
      patients' complaints, brain CT and MR imaging were required; showing bilateral
      epidural abscess. The patient was operated upon through a coronal incision and
      bifrontal craniotomy, draining both abscesses and removing their membranes.
      CONCLUSION: Epidural abscess constitute 5-25% of all the localized intracranial
      infections. Microorganism colonization may be produced by contiguous infection,
      hematogenous spread, open cranial trauma or as a consequence of neurosurgical
      intervention. Sinusitis is one of the most relevant causes of epidural abscesses,
      mostly in the frontal region. Bilateral occurrence is rare. In this paper a case
      of bilateral epidural abscess is pre-sent. Diagnosis criteria and treatment
      approaches are reviewed.

PMID- 18335157
TI  - [Claudio Galeno and the lateral ventricles].
AB  - Galen of Pergamon is considered one of the fathers of occidental medicine.
      Because of cultural and religious precepts at his time, many authors hypothesize
      that the anatomical concepts of Galen were derived from dissection of monkeys. In
      this paper, the authors analyzed the ventricular system, according to the
      anatomic and functional concepts described by Galen's early work. Knowing that
      his work was derived and or influenced from other preceding anatomists and
      physicians (specially Hipocrates of Cos), we present our investigation in two
      parts. In the first part, we present the influences of previous religious,
      philosophic, medical and anatomical theories over the galenic work. The
      "pregalenic era" can be divided in three periods: 1) the pretecnic era (ending in
      VI BC) in which the man have only a rudimentary knowledge of human anatomy, 2)
      the hellenistic science (from VI to III BC) and 3) the period comprised between
      III BC to Galenic period. In each of the three periods, we analyzed the
      neuroanatomic knowledge of the most important cultures.

PMID- 18335158
TI  - Video-supported analysis of Beggiatoa filament growth, breakage, and movement.
AB  - A marine Beggiatoa sp. was cultured in semi-solid agar with opposing oxygen
      sulfide gradients. Growth pattern, breakage of filaments for multiplication, and
      movement directions of Beggiatoa filaments in the transparent agar were
      investigated by time-lapse video recording. The initial doubling time of cells
      was 15.7 +/- 1.3 h (mean +/- SD) at room temperature. Filaments grew up to an
      average length of 1.7 +/- 0.2 mm, but filaments of up to approximately 6 mm were
      also present. First breakages of filaments occurred approximately 19 h after
      inoculation, and time-lapse movies illustrated that a parent filament could break
      into several daughter filaments within a few hours. In >20% of the cases,
      filament breakage occurred at the tip of a former loop. As filament breakage is
      accomplished by the presence of sacrificial cells, loop formation and the
      presence of sacrificial cells must coincide. We hypothesize that sacrificial
      cells enhance the chance of loop formation by interrupting the communication
      between two parts of one filament. With communication interrupted, these two
      parts of one filament can randomly move toward each other forming the tip of a
      loop at the sacrificial cell.

PMID- 18335159
TI  - Accuracy of perfusion-CT in predicting malignant middle cerebral artery brain
      infarction.
AB  - BACKGROUND: We performed a prospective study on patients with middle cerebral
      artery(MCA) ischemic stroke to evaluate the accuracy of perfusion-CT imaging(PCT)
      to predict the development of malignant brain infarction (MBI). METHODS: 106
      patients(women 37 %, mean age 65 years)underwent native cranial computed
      tomography (CCT), CT angiography(CTA) and PCT after a median of 2 h after stroke
      onset. We assessed the patency of the MCA and the area of tissue ischemia
      (AIT)according to cerebral blood flow(CBF), cerebral blood volume (CBV) and time
      to-peak (TTP)maps. Optimum sensitivity, specificity,positive (PPV) and negative
      predictive values (NPV) were calculated for the end-point MBI (= midline shift >
      5 mm or decompressive surgery) by means of receiver operating
      characteristics(ROC). RESULTS: 20 patients (19 %)developed a MBI. In these
      patients,a larger AIT was found in all perfusion maps as compared to the
      remaining patients (p < 0.001). All perfusion maps had a very high NPV (95.4-98.4
      %), a high sensitivity (85-95 %) and specificity (71.6-77.9 %) and only a
      moderate PPV (44-47.4 %). Best prediction was found for CBF maps with AIT of >
      27.9 % of the hemisphere. CONCLUSION: PCT allows the discrimination of patients
      without a relevant risk for MBI from those having a 50 % risk of MBI development.
      Due to the high sensitivity and specificity, PCT is a reliable tool in detecting
      MBI. Because of PCT's better availability, it is the method of choice at present
      for an early risk stratification of acute stroke patients.

PMID- 18335160
TI  - Neurotrophin and neuropeptide expression in mouse brain is regulated by knockout
      of the norepinephrine transporter.
AB  - Neurotrophins [e.g. nerve growth factor (NGF), brain-derived neurotrophic factor
      (BDNF) and neurotrophin-3 (NT-3)] and neuropeptides such as corticotropin
      releasing factor (CRF) are reported to contribute to the action of
      antidepressants (ADs). Norepinephrine transporter (NET) knockout (NETKO) mice
      represent a model of chronic AD treatment. In the present study, we examined
      brain-region-specific regulations of NT-3, NGF, BDNF and CRF at the mRNA and
      protein level in NET wild-type (NETWT) and NETKO mice by means of quantitative
      real-time PCR (qPCR) and two-site enzyme-linked immunosorbent assays (ELISAs),
      respectively. NETKO-induced changes were detected for NT-3 in olfactory bulb,
      brainstem and whole brain at the mRNA and for olfactory bulb at the protein
      level, for NGF mRNA and protein in olfactory bulb, cerebellum and brainstem and
      for CRF mRNA and protein in the hippocampus. In contrast, BDNF levels remained
      unaltered. Our results suggest that NETKO mice represent a useful model to
      examine gene regulation of downstream targets potentially involved in the action
      of ADs. We could delineate NT-3, NGF and CRF as being regulated in distinct brain
      regions by KO of the NET.

PMID- 18335161
TI  - Impact of endurance exercise on levodopa-associated cortisol release and force
      increase in patients with Parkinson's disease.
AB  - Levodopa (LD) application improves motor symptoms and reduces cortisol levels in
      patients with Parkinson's disease (PD). Endurance exercise enhances cortisol
      release in proportion to the intensity of the effort and thus may counteract the
      LD associated cortisol decrease. We measured levels of cortisol and LD over an 1
      h long interval following administration of soluble 200 mg LD/50 mg benserazide
      with concomitant maximal grip strength assessment in 16 PD patients under cued
      conditions during rest and endurance exercise. The motor response, the plasma
      levels of cortisol and LD did not significantly differ between both conditions.
      Cortisol concentrations significantly decreased even during exercise. Grip
      strength only significantly went up during rest. Endurance exercise did not
      counteract the LD associated decreased cortisol release. Since cortisol improves
      muscle function, the lack of increase in maximal grip strength following LD
      administration during exercise may contribute to reduced exercise capacity, which
      is reported by PD patients.

PMID- 18335162
TI  - Comprehensive analysis of polymorphisms throughout GAD1 gene: a family-based
      association study in schizophrenia.
AB  - Studies suggest that GAD1 gene is a functional candidate susceptibility gene for
      schizophrenia. In order to investigate the contribution of GAD1 gene to the
      etiology of schizophrenia in Chinese, we carried out a family-based association
      study between GAD1 gene and schizophrenia in 235 Chinese Han family trios. The
      GAD1 gene is comprehensively analyzed using a systematic mutation scan and the
      following-up association studies between common SNPs and schizophrenia in both
      single-locus and haplotype levels. Altogether, we have found 17 variants
      including 10 SNPs in 5'-flanking regions, 4 SNPs and one novel in-del in intronic
      regions and 2 SNPs (one novel SNP) in the 3'-untranslated region (UTR). Using the
      transmission disequilibrium test of the 9 common SNPs out of 17 variants,
      Significant evidence of SNP rs3791878-G allele in 5'-flanking region of GAD1 was
      preferentially transmitted to both the all offsprings of the trios (P = 0.0063,
      respectively; odds ratio = 1.83; 95% confidence interval: 1.26-2.65) and the male
      offsprings the trios (P = 0.0045, respectively; odds ratio = 2.21; 95% confidence
      interval: 1.37-3.56). Haplotype analysis suggested that rs3762556(C)-rs3791878(G)
      rs6755102(C) is the major risky haplotype preferentially transmitted in both all
      the trios and male-offspring trios (Global P = 0.016 and 0.012, respectively).
      The gender-dependent of the risk of SNP rs3791878 suggest the complexity of GAD1
      gene in schizophrenia. Given that the switch from G to T in SNP rs3791878 might
      cause the loss of ARNT and XBP1 transcriptional factor binding sites using a
      bioinformatics approach, our positive findings of this SNP support the hypothesis
      that the abruption of GAD1 gene is important to the risk of schizophrenia.

PMID- 18335163
TI  - Loss of thalamic serotonin transporters in early drug-naive Parkinson's disease
      patients is associated with tremor: an [(123)I]beta-CIT SPECT study.
AB  - In vitro studies revealed serotonin transporter (5-HTT) decline in Parkinson's
      disease (PD). Yet, few studies investigated thalamic 5-HTT in vivo and its effect
      on PD heterogeneity. We analyzed thalamic [(123)I]beta-CIT binding (mainly
      reflecting 5-HTT binding) in 32 drug-naive PD patients and 13 controls with
      SPECT. Twenty-six patients were examined twice (17 months apart). Based on UPDRS
      scores, we identified subgroups of patients with moderate/severe tremor (PD(T))
      and without tremor (PD(WT)) at the time of clinical diagnosis. Additionally,
      depressive symptoms were evaluated using the Beck Depression Inventory (BDI) at
      baseline. Mean thalamic specific to non-specific [(123)I]beta-CIT binding ratio
      was lower in patients when compared to controls, and further decreased during
      follow-up. At baseline, average thalamic ratio was significantly lower in the
      PD(T) than in the PD(WT) subgroup. No correlation was found between BDI scores
      and thalamic binding ratios. Our findings show decline of [(123)I]beta-CIT
      binding to thalamic 5-HTT in PD and its possible contribution to tremor onset.

PMID- 18335164
TI  - Metabolic activity of Siberian permafrost isolates, Psychrobacter arcticus and
      Exiguobacterium sibiricum, at low water activities.
AB  - The Siberian permafrost is an extreme, yet stable environment due to its
      continuously frozen state. Microbes maintain membrane potential and respiratory
      activity at average temperatures of -10 to -12 degrees C that concentrate solutes
      to an aw=0.90 (5 osm), The isolation of viable Psychrobacter arcticus sp. 273-4
      and Exiguobacterium sibiricum sp. 255-15 from ancient permafrost suggests that
      these bacteria have maintained some level of metabolic activity for thousands of
      years. Permafrost water activity was simulated using 1/2 TSB+2.79 m NaCl (5 osm)
      at and cells were held at 22 and 4 degrees C. Many cells reduced cyano
      tetrazolium chloride (CTC) indicating functioning electron transport systems.
      Increased membrane permeability was not responsible for this lack of electron
      transport, as more cells were determined to be intact by LIVE/DEAD staining than
      were reducing CTC. Low rates of aerobic respiration were determined by the slope
      of the reduced resazurin line for P. arcticus, and E. sibiricum. Tritiated
      leucine was incorporated into new proteins at rates indicating basal level
      metabolism. The continued membrane potential, electron transport and aerobic
      respiration, coupled with incorporation of radio-labeled leucine into cell
      material when incubated in high osmolarity media, show that some of the
      population is metabolically active under simulated in situ conditions.

PMID- 18335165
TI  - A novel metabolic network leads to enhanced citrate biogenesis in Pseudomonas
      fluorescens exposed to aluminum toxicity.
AB  - Aluminum (Al), an environmental toxin, is known to have a negative impact on
      various biological systems. However, some microbes have devised intricate
      mechanisms to combat the toxic influence of this trivalent metal. In this study,
      Pseudomonas fluorescens grown in malate invoked a unique metabolic shift to
      promote the synthesis of citrate, a metabolite involved in the sequestration of
      Al. Electrophoretic and spectrophotometric assays revealed several malate
      metabolizing enzymes including malate dehydrogenase (MDH) and malic enzyme (ME)
      displayed increases in activity and expression in the Al-treated cells. Whereas
      pyruvate dehydrogenase (PDH) also showed increased activity and expression in the
      Al-stressed cultures, phosphoenolpyruvate carboxykinase (PEPCK) displayed a
      marked diminution in the Al-treated cells. The upregulation of citrate synthase
      (CS) coupled with the diminished activities of aconitase (ACN) and NAD-isocitrate
      dehydrogenase (NAD-ICDH) appeared to be instrumental in the accumulation of
      citrate. HPLC experiments revealed high levels of citrate in the Al-stressed
      cultures. Thus, an Al-enriched environment provoked a metabolic shift in P.
      fluorescens dedicated to the conversion of malate to citrate.

PMID- 18335166
TI  - Characterization of a cryptic plasmid from a Greenland ice core Arthrobacter
      isolate and construction of a shuttle vector that replicates in psychrophilic
      high G+C Gram-positive recipients.
AB  - Over 60 Greenland glacial isolates were screened for plasmids and antibiotic
      resistance/sensitivity as the first step in establishing a genetic system.
      Sequence analysis of a small, cryptic, 1,950 bp plasmid, p54, from isolate GIC54,
      related to Arthrobacter agilis, showed a region similar to that found in theta
      replicating Rhodococcus plasmids. A 6,002 bp shuttle vector, pSVJ21, was
      constructed by ligating p54 and pUC18 and inserting a chloramphenicol acetyl
      transferase (CAT) cassette conferring chloramphenicol resistance. Candidate Gram
      positive recipients were chosen among glacial isolates based on phylogenetic
      relatedness, relatively short doubling times at low temperatures, sensitivity to
      antibiotics, and absence of indigenous plasmids. We developed an electroporation
      protocol and transformed seven isolates related to members of the Arthrobacter,
      Microbacterium, Curtobacterium, and Rhodoglobus genera with pSVJ21. Plasmid
      stability was demonstrated by successive transformation into Escherichia coli and
      four Gram-positive isolates, growth without antibiotic, and plasmid re-isolation.
      This shuttle vector and our transformation protocol provide the basis for genetic
      experiments with different high G+C Gram-positive hosts to study cold adaptation
      and expression of cold-active enzymes at low temperatures.

PMID- 18335167
TI  - Oxalate nephropathy with a granulomatous lesion due to excessive intake of
      peanuts.
AB  - A 65-year-old Japanese male developed renal dysfunction, showing proteinuria and
      marked urinary excretion of beta2-microglobulin. He had consumed approximately
      100-200 g peanuts and 750-1,000 ml beer every day for two or three months. He had
      previously been treated for hypertension with an angiotensin-converting enzyme
      inhibitor, enalapril. He then visited his primary-care doctor with mild fever,
      and renal dysfunction with mild diabetes mellitus were diagnosed. He was referred
      to our hospital, and because no diabetic retinopathy was observed by
      ophthalmological tests, renal biopsy examination was performed to clarify renal
      dysfunction. Renal biopsy specimens showed intimal thickening in the small
      arteries and interstitial nephritis with a granulomatous lesion, accompanied by
      oxalate crystals under polarized light. Glomeruli were unremarkable without any
      immunoglobulin deposition, and nodular lesions. Because he daily consumed a large
      amount of peanuts, oxalate nephropathy due to excessive intake of peanuts was
      strongly suspected. This case revealed that unusual food habits, including nuts,
      can cause oxalate nephropathy, and that close examination by renal biopsy was
      useful for clarifying the etiology of the unknown renal damage.

PMID- 18335168
TI  - Particle tracking to reveal gelation of hectorite dispersions.
AB  - Passive microrheological techniques using particle tracking have been developed
      for the study of the gelation of hectorite suspensions. By following the Brownian
      motion of the particles, it is possible to determine the increasing caging of the
      particles with time, as the system gels. Since only the Brownian motion is
      followed, the gelation process itself should not be affected by the measurement.
      As gelation proceeds the increasing heterogeneity of the particle environments
      can be monitored by a variety of measures, including kurtosis. An effective
      viscosity can be extracted from the measurements and used to indicate the
      gelation process.

PMID- 18335169
TI  - Gastrointestinal ulceration as a possible side effect of bevacizumab which may
      herald perforation.
AB  - Chemotherapy plus bevacizumab is currently considered as the standard 1st line
      treatment of advanced colorectal cancer (ACC). Whereas GI perforation is a known
      side effect of bevacizumab, the development of GI ulcers has not been reported.
      We identified 18 patients with ACC who participated in a phase III multicentre
      trial which included chemotherapy and bevacizumab, who developed a GI ulcer (n =
      6), perforation (n = 8) or both (n = 4). The risk of developing a symptomatic GI
      ulcer or perforation was 1.3% and 1.6%, respectively. Central review of the
      histology specimens showed ulceration and/or granulation tissue with
      neovascularisation. The majority (89%) of events developed early during
      treatment. Given these observations, as well as the relationship between VEGF and
      mucosal injury healing, we suggest that GI ulcers may occur as a side effect of
      treatment with bevacizumab and may herald perforation.

PMID- 18335171
TI  - Arsenic and fluoride in the groundwater of Mexico.
AB  - Concentrations of arsenic and fluoride above Mexican drinking water standards
      have been detected in aquifers of various areas of Mexico. This contamination has
      been found to be mainly caused by natural sources. However, the specific
      processes releasing these toxic elements into groundwater have been determined in
      a few zones only. Many studies, focused on arsenic-related health effects, have
      been performed at Comarca Lagunera in northern Mexico. High concentrations of
      fluoride in water were also found in this area. The origin of the arsenic there
      is still controversial. Groundwater in active mining areas has been polluted by
      both natural and anthropogenic sources. Arsenic-rich minerals contaminate the
      fractured limestone aquifer at Zimapan, Central Mexico. Tailings and deposits
      smelter-rich fumes polluted the shallow granular aquifer. Arsenic contamination
      has also been reported in the San Antonio-El Triunfo mining zone, southern Baja
      California, and Santa Maria de la Paz, in San Luis Potosi state. Even in the
      absence of mining activities, hydrogeochemistry and statistical techniques showed
      that arsenopyrite oxidation may also contaminate water, as in the case of the
      Independencia aquifer in the Mexican Altiplano. High concentrations of arsenic
      have also been detected in geothermal areas like Los Azufres, Los Humeros, and
      Acoculco. Prevalence of dental fluorosis was revealed by epidemiological studies
      in Aguascalientes and San Luis Potosi states. Presence of fluoride in water
      results from dissolution of acid-volcanic rocks. In Mexico, groundwater supplies
      most drinking water. Current knowledge and the geology of Mexico indicate the
      need to include arsenic and fluoride determinations in groundwater on a routine
      basis, and to develop interdisciplinary studies to assess the contaminant's
      sources in all enriched areas.

PMID- 18335170
TI  - Characterization of the mechanism of zidovudine uptake by rat conditionally
      immortalized syncytiotrophoblast cell line TR-TBT.
AB  - PURPOSE: To characterize the uptake mechanism of zidovudine (AZT), a nucleoside
      reverse transcriptase inhibitor, in syncytiotrophoblast cells using the TR-TBT
      18d-1 cell line previously established by our group. MATERIALS AND METHODS: The
      effects of several transporter inhibitors on the initial and steady-state apical
      uptake of AZT by TR-TBT 18d-1 were characterized, in order to identify the
      transporter(s) involved. RESULTS: Initial uptake of AZT was sodium-independent
      and saturable; the K(m) value was about 16 microM. Nitrobenzylthioinosine
      (NBMPR), probenecid and cimetidine each had little effect on the saturable AZT
      uptake, indicating that well characterized transporters, such as organic anion
      transporters (OATs and OATPs), organic cation transporters (OCTs) and
      equilibrative nucleoside transporters (ENTs), are not involved. However,
      thymidine and 2'-deoxyuridine strongly inhibited AZT uptake. These results
      suggest that an unidentified nucleoside uptake transporter is responsible for the
      uptake of AZT. Cyclosporin A, Ko143 and probenecid had little effect on AZT
      accumulation by TR-TBT 18d-1 cells, suggesting that transporter-mediated efflux
      of AZT is not substantial. CONCLUSION: Our results indicate that saturable AZT
      uptake into TR-TBT 18d-1 is mediated by a so-far-unidentified transporter.

PMID- 18335172
TI  - Saharan dust clouds and human health in the English-speaking Caribbean: what we
      know and don't know.
AB  - Dust clouds travel across the Atlantic to the Americas and the Caribbean Islands.
      This long-range transport of dust leads to clouds that are enriched with small
      particles less than 10 microm aerodynamic diameter (PM10) which can reach human
      airways. The dust clouds also bring pollen, microbes, insects and chemicals, all
      of which could potentially have a negative impact on human health. This has led
      to a small number of retrospective studies being conducted on the islands of
      Barbados and Trinidad to look at possible associations between dust cover and
      acute asthma admissions to Emergency Rooms. The results have been conflicting.
      This review examines these studies, offers possible explanations for the
      differences in results, and suggests that there is a need for a prospective
      Caribbean-wide study to assess fully any relationship between African dust clouds
      and human respiratory and cardiovascular diseases.

PMID- 18335173
TI  - Occurrence and problems of high fluoride waters in Turkey: an overview.
AB  - Endemic dental fluorosis was first observed in Turkey in Isparta Province,
      located in the SW of Anatolia, with mottled enamel related to the high levels of
      fluoride (1.5-4.0 ppm) in drinking waters, about 55 years ago. The origin of
      fluoride was attributed to the contents of minerals in volcanic rocks, consisting
      of pyroxene, hornblende, biotite, fluorapatite and glassy groundmass minerals. It
      was also reported about 35 years ago that severe dental and skeletal fluorosis
      has been observed in human beings and livestock in Dogubeyazit and Caldiran
      areas, located around Tendurek Volcano in eastern Turkey, where natural waters
      contained fluoride levels between 2.5 and 12.5 ppm. It was hypothesised that
      fluoride, which might be transported by fumaroles or escaped from devitrified
      lavas, could be held on the surface of some minerals and then exchanged with OH(
      ) in ground waters with high pH at the foothills of the young Tendurek Volcano.
      Endemic dental and skeletal fluorosis was also observed in the inhabitants in
      Kizilcaoren Village of Beylikova Town in Eskisehir Province situated in the
      midwest of Turkey, where the fluoride content of the drinking waters ranged from
      3.9 to 4.8 ppm. The origin of high fluoride in the natural waters was related to
      the fluorspar deposits, occurring in the catchment area near the village. During
      the survey in the Gullu Village of Esme-Usak, located in south-midwest of Turkey,
      it was observed that most of the inhabitants born and raised in the village and
      aged between 10 and 30 years, showed mild to moderate levels of mottled enamel.
      The fluoride contents of the deep well waters used for drinking in the village,
      varied from 0.7 to 2.0 ppm. Amorphous microscopic fluorite existing in the
      Pliocene lake limestones was considered as a possible origin of fluoride in the
      waters.

PMID- 18335174
TI  - Visual outcomes and graft survival following corneal transplants: the need for an
      Irish National Corneal Transplant Registry.
AB  - PURPOSE: To evaluate visual outcomes and corneal graft survival at 12 months
      postoperatively, and to demonstrate the need for an Irish National Corneal
      Transplant Registry. METHODS: Retrospective, single surgeon, single center,
      analysis of 44 consecutive corneal transplants was performed between 2001 and
      2005. RESULTS: Forty-four eyes of 41 patients underwent penetrating keratoplasty
      (n = 37), lamellar keratoplasty (n = 6) or limbal graft (n = 1). Indications for
      surgery (%) were keratoconus 45.45%; bullous keratopathy 2.7%; graft failure 9%;
      Fuchs endothelial dystrophy 2 4.5%; Irido corneal endothelial syndrome 2.27% and
      tectonic 15.9%. Visual outcome at 1 year (%) were as follows: improved by one or
      more Snellen lines (79.5%); disimproved by one or more Snellen lines (9%);
      unchanged (11.5%). Graft survival at 1 year was 93%. DISCUSSION: Although our
      findings compare favourably with those of the Australian Corneal Graft Registry,
      there is no Irish Corneal Transplant Registry with which to compare our results.

PMID- 18335175
TI  - A novel fully enzymatic method for determining glucose and 1,5-anhydro-D-glucitol
      in serum of one cuvette.
AB  - The aim of the study was to set up a novel fully enzymatic method for screening
      glucose and 1,5-anhydro-D-glucitol (1,5-AG) in one cuvette. We have determined
      glucose and 1,5-AG, based on glucokinase (GK) converting glucose to G6P, a
      compound that can be catalyzed ultimately into 6-PGA by G-6PD and its coenzyme
      NADP(+), and then calculated glucose concentration according to absorbance
      variety. Furthermore, pyranose oxidase was used to oxidize 1,5-AG with the
      formation of 1, 5-anhydro-fructose and H(2)O(2). Measurement was done according
      to Trinder's reaction principle. The mean within-run and day-to-day precision
      (CV) of this method for glucose was 0.88% and 1.4%, and also that for 1,5-AG was
      1.05% and 1.94%, respectively. The mean recovery rate of two targets was 100.2%
      and 101.6%, respectively. The correlation (R(2)) between the results of 1,5-AG
      obtained with our proposed method (y) and those obtained with LanaAG method (x)
      was 0.999 (y=1.002x-0.675 micromol/l; n=86), and the correlation (R(2)) of
      glucose between the results obtained with our GK method (y) and those obtained
      with recommendatory hexokinase method (x) was 0.9999 (y=1.0043x+0.1229 mmol/l;
      n=86). The reference range (95%) of serological glucose and 1,5-AG was 3.7 to 5.7
      mmol/l (4.70+/-0.51 mmol/l) and 83.1 to 240.7 micromol/l (161.9+/-40.2
      micromol/l), respectively; and there was no difference with age and sex (P>0.05).
      This newly developed method was dependable and steady-going, with analysis
      automatization, and allows quicker and easier measurement of serum glucose and
      1,5-AG in one identical reaction cuvette in-phase than previously described
      methods.

PMID- 18335176
TI  - Idiopathic retroperitoneal fibrosis: a rare disease to be treated by an
      internist.

PMID- 18335179
TI  - [Multicentric randomised controlled trials in Germany: overview and interim
      analysis 1 year after inclusion of in the rubric "Clinical Trials"].
AB  - BACKGROUND: For 1 year now, German surgical multicentric randomised controlled
      trials (MRCT) in Germany may be included under the heading "Clinical Trials" in
      our monthly updated trial list. MATERIAL AND METHODS: Quantitative and
      qualitative analysis of MRCT presented in the trial list was performed to give an
      overview and interim statement 1 year after implementation of the journal heading
      "Clinical Trials". RESULTS: In 1 year, the study list increased from four to
      eleven MRCT and the numbers of randomized patients from 396 to 1511. The MRCT
      show distinct differences regarding funding sources and reimbursement for
      participating centres per patient included. The study protocols of four of 11
      MRCT were published in scientific journals. CONCLUSION: The new regular heading
      gives important details about ongoing surgical trials in Germany. The steady
      growth of trials and recruited patients demonstrates the practicability of
      randomized controlled trials in surgery.

PMID- 18335180
TI  - [Short biography of Professor Martin Allgower: M.D. FACS (Hon), FRCS (Hon), ASA
      (Hon), 1917-2007].

PMID- 18335181
TI  - [Results of sigma resection in acute complicated diverticulitis : method and time
      of surgical intervention].
AB  - BACKGROUND: The aim of this study was to check the results of laparoscopic
      sigmoid resection for sigmoid diverticular disease with respect to stage of
      inflammation and time of surgical intervention. PATIENTS AND METHODS: All
      patients were divided into four groups: uncomplicated (Group 1) vs complicated
      diverticular disease (Group 2), and depending on surgical intervention in early
      elective (4-8 days, Group A) vs late elective sigmoid resection (4-6 weeks, Group
      B). RESULTS: At total of 244 patients underwent laparoscopically-assisted
      resection during the examination period. Differences in favor of Group 1 were
      found in duration of surgery (153 min vs 167 min), postoperative wound infections
      (3.55% vs 15.5%), and postoperative hospitalization period (12.2 days vs 14.6
      days). Group A had more conversions (7.8% vs 0.9%), more minor complications
      (25.9% vs 12.9%), and more wound infections (16.4% vs 4.6%) than Group B.
      CONCLUSIONS: Laparoscopic sigmoid resection can be performed in cases of
      complicated diverticulitis without significantly increasing their overall
      morbidity. Because of the lower complication rate, we recommend that patients
      with acute sigmoid diverticulitis receive initial antibiotic treatment and then
      undergo late elective laparoscopic sigmoid resection.

PMID- 18335182
TI  - [Peritonitis: attempt to evaluate therapeutic surgical options].
AB  - The choice of optimal concept in the therapy of severe peritonitis is essential
      to outcome. In approximately 10-15% of patients suffering severe peritonitis,
      single-stage surgery is not sufficient and additional operative therapy is
      required. Different therapeutic strategies such as the open-package procedure,
      staged abdominal repair, and on-demand relaparotomy have been developed for these
      situations. However, it is difficult to compare the effectiveness of each regimen
      because stratification tools are lacking. This paper describes advantages and
      disadvantages of the various therapeutic options in peritonitis and their
      clinical implementation.

PMID- 18335183
TI  - [Antimicrobial and antimycotic therapy of intra-abdominal infections].
AB  - Antimicrobial chemotherapy is a cornerstone in the treatment of intra-abdominal
      infections (IAI). The initiation of initial antibiotic therapy must immediately
      follow the diagnosis of IAI. Selection of the antimicrobial agent is based on the
      expected pathogenic bacterial spectrum as a calculated empirical therapy. It is
      impossible to give general recommendations concerning the selection of a certain
      class of antimicrobial chemotherapeutics, since all available clinical trials
      were designed to prove noninferiority to the comparator product. Nevertheless
      several societies developed guidelines and recommendations based on the multitude
      of clinical trials investigating antimicrobial chemotherapeutics. The antibiotic
      therapy of postoperative peritonitis has to be implemented according to the
      patient's risk profile (antibiotic pretreatment, multiresistant pathogens,
      hospital epidemiology). The development of invasive peritoneal mycoses is rare.
      The therapy should be guided by the results of the microbiological work-up of the
      intraperitoneal cultures.

PMID- 18335184
TI  - [Pharmacology and clinical relevance of vasopressin antagonists].
AB  - As vasopressin receptors are found in many different tissues, vasopressin
      antagonists may benefit the treatment of numerous disorders. Effects of
      vasopressin via V1(a) and V2 receptors are closely implicated in a variety of
      water-retaining diseases and cardiovascular diseases, including heart failure,
      hyponatremia, hypertension, renal diseases, syndrome of inappropriate
      antidiuretic hormone secretion, cirrhosis, and ocular hypertension. Furthermore,
      V1(a) vasopressin antagonists might be useful in cerebral ischemia and stroke,
      Raynaud's disease, dysmenorrhoea and tocolytic treatment. V1(b) selective
      vasopressin antagonists are discussed in terms of their usefulness in the
      treatment of emotional and psychiatric disorders. The vaptans are vasopressin
      receptor antagonists with V1(a) (relcovaptan) or V2 (tolvaptan, lixivaptan,
      satavaptan) selectivity or non-selective activity (conivaptan). Conivaptan is the
      first vaptan which has been approved by the FDA for the treatment of euvolemic
      hyponatremia. For further indications such as congenital heart failure, studies
      are going on.

PMID- 18335185
TI  - Involvement of (pro)renin receptor in the glomerular filtration barrier.
AB  - (Pro)renin receptor-bound prorenin not only causes the generation of angiotensin
      II via the nonproteolytic activation of prorenin, it also activates the
      receptor's own intracellular signaling pathways independent of the generated
      angiotensin II. Within the kidneys, the (pro)renin receptor is not only present
      in the glomerular mesangium, it is also abundant in podocytes, which play an
      important role in the maintenance of the glomerular filtration barrier. Recent in
      vivo studies have demonstrated that the overexpression of the (pro)renin receptor
      to a degree similar to that observed in hypertensive rat kidneys leads to slowly
      progressive nephropathy with proteinuria. In addition, the handle region peptide,
      which acts as a decoy peptide and competitively inhibits the binding of prorenin
      to the receptor, is more beneficial than an angiotensin-converting enzyme
      inhibitor with regard to alleviating proteinuria and glomerulosclerosis in
      experimental animal models of diabetes and essential hypertension. Thus, the
      (pro)renin receptor may be upregulated in podocytes under hypertensive conditions
      and may contribute to the breakdown of the glomerular filtration barrier.

PMID- 18335186
TI  - Analysis of human MDM4 variants in papillary thyroid carcinomas reveals new
      potential markers of cancer properties.
AB  - A wild-type (wt) p53 gene characterizes thyroid tumors, except for the rare
      anaplastic histotype. Because p53 inactivation is a prerequisite for tumor
      development, alterations of p53 regulators represent an alternative way to impair
      p53 function. Indeed, murine double minute 2 (MDM2), the main p53 negative
      regulator, is overexpressed in many tumor histotypes including those of the
      thyroid. A new p53 regulator, MDM4 (a.k.a. MDMX or HDMX) an analog of MDM2,
      represents a new oncogene although its impact on tumor properties remains largely
      unexplored. We estimated levels of MDM2, MDM4, and its variants, MDM4-S
      (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary
      thyroid carcinomas (PTC), characterized by wt tumor protein 53, in comparison to
      matched contra-lateral lobe normal tissue. Further, we evaluated the association
      between expression levels of these genes and the histopathological features of
      tumors. Quantitative real-time polymerase chain reaction revealed a highly
      significant downregulation of MDM4 mRNA in tumor tissue compared to control
      tissue (P<0.0001), a finding confirmed by western blot on a subset of 20 tissue
      pairs. Moreover, the tumor-to-normal ratio of MDM4 levels for each individual was
      significantly lower in late tumor stages, suggesting a specific downregulation of
      MDM4 expression with tumor progression. In comparison, MDM2 messenger RNA (mRNA)
      and protein levels were frequently upregulated with no correlation with MDM4
      levels. Lastly, we frequently detected overexpression of MDM4-S mRNA and presence
      of the aberrant form, MDM4-211 in this tumor group. These findings indicate that
      MDM4 alterations are a frequent event in PTC. It is worthy to note that the
      significant downregulation of full-length MDM4 in PTC reveals a novel status of
      this factor in human cancer that counsels careful evaluation of its role in human
      tumorigenesis and of its potential as therapeutic target.

PMID- 18335187
TI  - PLZF and the (pro)renin receptor.
AB  - For many years, angiotensin II with its respective receptors was considered to be
      the only effector molecule within the renin-angiotensin system. Nevertheless,
      several studies indicated that renin (the enzyme catalyzing the generation of
      angiotensin I) and its enzymatically inactive precursor prorenin may have an
      angiotensin-II-independent (patho)physiological significance. In 2002, a specific
      (pro)renin receptor ((P)RR)) which increases the enzymatic activity of its
      ligands and induces an intrinsic activity upon ligand binding has been published.
      Recently, our group has demonstrated a novel (P)RR signal transduction pathway
      involving direct protein-protein interaction between the (P)RR and the
      transcription factor promyelocytic zinc finger protein (PLZF) and the nuclear
      translocation of PLZF upon renin stimulation. Downstream effects of (P)RR
      activation by renin included repression of the (P)RR itself and induction of the
      p85alpha subunit of the phosphatidylinositol-3 kinase (PI3K-p85alpha) as well as
      an increase in proliferation and a decrease in apoptotic activity. Various animal
      models demonstrated that inhibition of prorenin binding to the (P)RR can prevent
      or even abolish the development of cardiac fibrosis and diabetic nephropathy via
      angiotensin-II-independent mechanisms. Additional studies that verify these
      remarkable findings are needed. Moreover, the potency of aliskiren (the first
      orally active renin inhibitor in the market) to interfere with a putatively
      detrimental binding of (pro)renin to the (P)RR is of particular interest and has
      to be elucidated.

PMID- 18335188
TI  - Enhanced functionality of T cell receptor-redirected T cells is defined by the
      transgene cassette.
AB  - The transfer of T cell receptor (TCR) genes allows to endow T cells with a new
      antigen specificity. For clinical applications of TCR-redirected T cells,
      efficient functional expression of the transgenic TCR is a key prerequisite.
      Here, we compared the influence of the transgene cassette on the expression and
      function of the murine TCR P14 (recognizing a LCMV gp33 epitope) and the human
      TCR WT-1 (recognizing an epitope of the tumor-associated antigen WT-1). We
      constructed different vectors, in which TCRalpha- and beta-chain genes were
      either (a) linked by an internal ribosomal entry site (IRES), (b) combined by a
      2A peptide, or (c) introduced into two individual retroviral constructs. While in
      a TCR-deficient T cell line TCR P14 was expressed equally well by all constructs,
      we found that IRES- but not 2A-employing TCR expression is hampered in a TCR
      bearing cell line and in primary murine T cells where the transgenic TCR has to
      compete with endogenous TCR chains. Similarly, 2A-linked TCR WT-1 genes yielded
      highest expression and function as measured by tetramer binding and peptide
      specific IFN-gamma secretion. Differences in expression were independent of copy
      number integration as shown by real-time PCR. Thus, linking TCRalpha- and beta
      chain genes by a 2A peptide is superior to an IRES for TCR expression and T cell
      function.

PMID- 18335189
TI  - Impaired spatial memory and altered dendritic spine morphology in angiotensin II
      type 2 receptor-deficient mice.
AB  - Mental retardation is the most frequent cause of serious handicap in children and
      young adults. Mutations in the human angiotensin II type 2 receptor (AT2) have
      been implicated in X-linked forms of mental retardation. We here demonstrate that
      mice lacking the AT2 receptor gene are significantly impaired in their
      performance in a spatial memory task and in a one-way active avoidance task. As
      no difference was observed between the genotypes in fear conditioning, the
      detected deficit in spatial memory may not relate to fear. Notably, receptor
      knockout mice showed increased motility in an activity meter and elevated plus
      maze. Importantly, these mice are characterized by abnormal dendritic spine
      morphology and length, both features also found to be associated with some cases
      of mental retardation. These findings suggest a crucial role of AT2 in normal
      brain function and that dysfunction of the receptor has impact on brain
      development and ultrastructural morphology with distinct consequences on learning
      and memory.

PMID- 18335190
TI  - The Crohn's disease susceptibility gene DLG5 as a member of the CARD interaction
      network.
AB  - Discs large homolog 5 (DLG5), a member of the membrane-associated guanylate
      kinase (MAGUK) family of scaffolding proteins, has been associated with Crohn's
      disease (CD), but its role in the pathogenesis of this inflammatory bowel disease
      is disputed. Here, we used sequence comparisons and phylogenies to analyse the
      DLG5 gene and its protein product. We identified a 5' exon, which codes for an N
      terminal caspase recruitment domain (CARD) and experimentally confirmed its
      expression in colonic tissue. DLG5 shares this new domain with nucleotide-binding
      oligomerisation domain containing 2 (NOD2); the first CD susceptibility factor
      identified in genetic studies. An extensive phylogenetic analysis redefines the
      family organisation of the MAGUK proteins: DLG5 is closely related to CARD10,
      CARD11 and CARD14, CARD-containing proteins which initiate pro-inflammatory
      NFkappaB signalling, but not to DLG1-4, previously considered the closest related
      proteins. Therefore, we suggest renaming DLG5 to correctly annotate the gene in
      its phylogenetic and functional context. Our study provides evidence that the
      scaffolding protein DLG5 belongs to the CARD protein family. Thus, DLG5 likely
      acts in the regulation of NFkB activation or caspase activation as part of host
      defence mechanisms. As there is substantial crosstalk between CARD-mediated
      pathways, both CD susceptibility genes, NOD2 and DLG5, may interact functionally
      to contribute to CD risk.

PMID- 18335191
TI  - [Adherence to neurologic treatment. Lessons from multiple sclerosis].
AB  - In light of increasing prevalence rates of chronic conditions and a growing
      elderly population, patients' nonadherence to medical regimes reflects a
      significant problem in modern health care. In the past, patients were primarily
      held responsible for problematic adherence. Over the past decades this attitude
      has changed dramatically, and it is now acknowledged that lack of adherence
      reflects a problem requiring different approaches and interventions on many
      different levels. Here we highlight central aspects and consequences of adherence
      problems in long-term therapy. Factors affecting treatment motivation in multiple
      sclerosis patients are summarized focusing on neurologic treatment issues, and
      specific intervention strategies for patients, doctors, and nurses are discussed.

PMID- 18335192
TI  - [Current situation and future perspectives of digital mammography].
AB  - Digital mammography has extensively replaced conventional film screen mammography
      and is now the standard in combination with soft copy reading in clinical as well
      as screening mammography. Large international multicenter studies demonstrate an
      equivalent or superior detection rate of breast cancers by digital in comparison
      to conventional mammography especially in dense breasts, premenopausal and
      perimenopausal women and women less than 50 years old. Computer-aided detection
      (CAD) is important for the experienced investigator (increased specificity).
      Digital mammography also offers further options, such as tomosynthesis, digital
      contrast-enhanced mammography and the combination of digital mammography and
      ultrasound. The future in breast diagnosis will be the fusion of images from
      different digital systems.

PMID- 18335193
TI  - [Stromal tumor of the prostate of uncertain malignant potential. A diagnostic
      rarity].
AB  - Stromal tumor of the prostate of uncertain malignant potential (STUMP) is an
      extremely rare entity. The clinical symptoms are nonspecific for this tumor. An
      abnormal digital rectal examination or an elevated prostate-specific antigen
      level is possible but not obligatory. The tumor has a high recurrence rate and
      could develop a sarcomatous dedifferentiation. Therapy varies from a wait-and-see
      approach to a radical prostatectomy. We report the case of a 74-year-old patient
      with a STUMP. Based on the case, the clinical, diagnostic, and therapeutic
      aspects of this rare tumor are discussed.

PMID- 18335194
TI  - [Overview and evolving strategies of ventral hernia repair].
AB  - Incisional hernias occur in 5-10% of patients who have undergone laparotomy and
      are associated with high morbidity and significant socioeconomic costs.
      Techniques for reinforcing and/or replacing the abdominal wall with alloplastic
      meshes have reduced the recurrence rate in comparison to suture techniques from
      about 40% to less than 10%. A number of mesh types and surgical repair procedures
      are available, namely the onlay, inlay, sublay, underlay, and intraperitoneal
      onlay mesh (IPOM) techniques. Evolving strategies include precise criteria for
      incorporating patient body type, risk factors for recurrence, hernia morphology,
      and the available biomaterials into the planning of the surgical approach. The
      authors herein present an overview of the current surgical trends, focusing on
      mesh reinforcement (sublay technique) and mesh replacement (IPOM technique).
      Additionally, they review a classification of incisional hernias that is self
      explanatory, practicable in routine clinical practice, and based on the
      cornerstones of morphology, hernia size, and risk factors for recurrence.
      Evidence for the indications and limitations of the main surgical repair
      techniques are illustrated and discussed.

PMID- 18335195
TI  - [Relevance of hospitals participating in the DRG calculation for the development
      of the G-DRG system].
AB  - Since the G-DRG system was established for remuneration of inpatient treatment,
      hospitals may offer the cost data of their cases as a database for the
      calculation of new DRGs. Therefore, the DRGs will be only as good as the cost
      data offered. These hospitals must be interested in offering perfect data, since
      this is the only option to optimize the DRG system.

PMID- 18335196
TI  - [Laser vaporization of the prostate: all as it should be?].
AB  - Laser vaporization of the prostate currently occupies a prominent place among the
      surgical options for treatment of benign prostatic syndrome. Particularly the so
      called GreenLight laser vaporization with the KTP (80 W) or LBO (120 W) laser has
      become remarkably widespread throughout the world. There are already 100 of these
      GreenLight laser systems in use in Germany alone. The introduction of a separate
      DRG for "laser vaporization" is expected to further increase the significance of
      this surgical technique. The aim of this study is to evaluate laser vaporization
      as a whole and to identify possible differences between the different lasers.

PMID- 18335197
TI  - [Nephrectomy, donor nephrectomy, and partial kidney resection: indications for
      robot-assisted renal surgery].
AB  - Laparoscopic renal surgery in experienced hands is an alternative to open
      surgery, although the technical difficulty of, for example, intracorporeal
      suturing and concerns over warm ischemia time for partial nephrectomy are
      limitations. Previous work has demonstrated that suturing with the robotic da
      Vinci system is easier compared with laparoscopy. The purpose of this report was
      to evaluate the feasibility of robot-assisted da Vinci renal surgery. In our
      study, the learning curve, complication rate, and operative time were short and
      the intraoperative technical movements were intuitive with the da Vinci Surgical
      System. In our opinion, robot-assisted surgery will allow urologists to perform
      complex procedures with great precision, confidence, and excellent results in
      renal surgery.

PMID- 18335198
TI  - [Robot-assisted laparoscopic radical cystectomy].
AB  - Recent reports have demonstrated that robot-assisted laparoscopic cystectomy is
      technically feasible. However, wide-spread acceptance of this promising technique
      is limited due to long operating times and lacking long-term data especially on
      oncological outcome. After establishing robot-assisted laparoscopic prostatectomy
      (n=250) we report technical and functional results of a large series of patients
      undergoing laparoscopic cystectomy with the da Vinci surgical system (DVSS).27
      patients (24 males) underwent laparoscopic radical cystectomy with the DVSS
      (Intuitive Surgical) between Jan 2004 and Dec 2006. Indications for cystectomy
      were muscle-invasive transitional cell carcinoma (TCC) or leiomyosarcoma of the
      urinary bladder (n=24) and bladder shrinking following prior radiotherapy for TCC
      (n=3). A pelvic lymphadenectomy was routine part of the procedure. Urinary
      diversions were ilieal conduits (n=19) and ileal neobladders (n=8). Mean
      operating time was 340 minutes (range 150-450) with a mean blood loss of 301 mL
      (range 50-550). The mean number of lymph nodes retrieved during lymphadenectomy
      was 23. Surgical margins were negative except in one case. After a mean follow-up
      of 10.2 months, 2 perioperative (anastomotic leakage, adhesions) and 3
      postoperative complications (ileus, intestinal fistula) occurred. 6/7 patients
      reported satisfying erectile function following nerve-sparing surgery. Day-time
      continence was completely restored after a mean 3.5 months in 7/8 patients.Robot
      assisted laparoscopic cystectomy is a safe procedure. Satisfying functional and
      oncological short-term results can be achieved within acceptable operating time
      limits.

PMID- 18335199
TI  - Fine mapping and candidate gene analysis of hwh1 and hwh2, a set of complementary
      genes controlling hybrid breakdown in rice.
AB  - Hybrid breakdown (HB), a phenomenon of reduced viability or fertility accompanied
      with retarded growth in hybrid progenies, often arises in the offspring of
      intersubspecific hybrids between indica and japonica in rice. We detected HB
      plants in F8 recombinant inbred lines derived from the cross between an indica
      variety, Milyang 23, and a japonica variety, Tong 88-7. HB plants showed retarded
      growth, with fewer tillers and spikelets. Genetic analysis revealed that HB was
      controlled by the complementary action of two recessive genes, hwh1 and hwh2,
      originating from each of both parents, which were fine-mapped on the short arm of
      chromosome 2 and on the near centromere region of the long arm of chromosome 11,
      respectively. A comparison of the sequences of candidate genes among both parents
      and HB plants revealed that hwh1 encoded a putative glucose-methanol-choline
      oxidoreductase with one amino acid change compared to Hwh1 and that hwh2 probably
      encoded a putative hexose transporter with a six amino acid insertion compared to
      Hwh2. Investigation of the distribution of these alleles among 54 japonica and
      indica cultivars using candidate gene-based markers suggested that the two loci
      might be involved in developing reproductive barriers between two subspecies.

PMID- 18335200
TI  - Genomic amplification of the Gret1 retroelement in white-fruited accessions of
      wild vitis and interspecific hybrids.
AB  - Retrotransposons are retrovirus-related mobile sequences that have the potential
      to replicate via RNA intermediates and increase the genome size by insertion into
      new sites. The retroelement, Gret1, has been identified as playing a key role in
      generating fruit color variation in cultivated grape (Vitis vinifera L.) due to
      its insertion into the promoter of VvMybA1. Fruit color variation is an important
      distinguishing feature of cultivated grapes and virtually no fruit color
      variation is observed in wild grape species. The presence and relative copy
      number of Gret1 was assessed using quantitative PCR on 22 different Vitis
      species, only four of which (plus interspecific hybrids) are known to contain
      white accessions. Gret1 copy number was observed to vary by species as well as by
      color within species and was significantly higher in white-fruited accessions
      across all taxa tested. Additionally, genomic regions surrounding Gret1 insertion
      were sequenced in white V. vinifera, hybrid, V. labrusca, V. aestivalis, and V.
      riparia accessions.

PMID- 18335201
TI  - Quantitative trait loci for slow-rusting resistance in wheat to leaf rust and
      stripe rust identified with multi-environment analysis.
AB  - Rust diseases are a major cause of yield loss in wheat worldwide, and are often
      controlled through the incorporation of resistance genes using conventional
      phenotypic selection methods. Slow-rusting resistance genes are expressed
      quantitatively and are typically small in genetic effect thereby requiring
      multiple genes to provide adequate protection against pathogens. These effects
      are valuable and are generally considered to confer durable resistance. Therefore
      an understanding of the chromosomal locations of such genes and their biological
      effects are important in order to ensure they are suitably deployed in elite
      germplasm. Attila is an important wheat grown throughout the world and is used as
      a slow-rusting donor in international spring wheat breeding programs. This study
      identified chromosomal regions associated with leaf rust and stripe rust
      resistances in a cross between Attila and a susceptible parent, Avocet-S,
      evaluated over 3 years in the field. Genotypic variation for both rusts was large
      and repeatable with line-mean heritabilities of 94% for leaf rust resistance and
      87% for stripe rust. Three loci, including Lr46/Yr29 on chromosome 1BL, were
      shown to provide resistance to leaf rust whereas six loci with small effects
      conferred stripe rust resistance, with a seventh locus having an effect only by
      epistasis. Disease scoring over three different years enabled inferences to be
      made relating to stripe rust pathogen strains that predominated in different
      years.

PMID- 18335202
TI  - Nuclear and cytoplasmic genetic diversity in weed beet and sugar beet accessions
      compared to wild relatives: new insights into the genetic relationships within
      the Beta vulgaris complex species.
AB  - Hybridization between cultivated species and their wild relatives is now widely
      considered to be common. In the Beta vulgaris complex, the sugar beet seed
      multiplication areas have been the scene of inadvertent pollination of sugar beet
      seed bearers by wild ruderal pollen donors, generating a weedy form of beet which
      infests sugar beet fields in European countries. Up to now, investigations of
      evolutionary dynamics of genetic diversity within the B. vulgaris complex were
      addressed using few genetical markers and few accessions. In this study, we
      tackled this issue using a panel of complementary markers: five nuclear
      microsatellite loci, four mitochondrial minisatellite loci and one chloroplastic
      PCR-RFLP marker. We sampled 1,640 individuals that illustrate the actual
      distribution of inland ruderal beets of South Western France, weed beets and wild
      sea beets of northern France as well as the diversity of 35 contemporary European
      diploid cultivars. Nuclear genetic diversity in weed beets appeared to be as high
      as those of ruderal beets and sea beets, whereas the narrowness of cultivar
      accessions was confirmed. This genetic bottleneck in cultivars is even more
      important in the cytoplasmic genome as only one haplotype was found among all
      sugar beet cultivars. The large majority of weed beet populations also presented
      this unique cytoplasmic haplotype, as expected owing to their maternal cultivated
      origin. Nonetheless, various cytoplasmic haplotypes were found within three
      populations of weed beets, implying wild-to-weed seed flows. Finally, our
      findings gave new insights into the genetical relationships between the
      components of the B. vulgaris complex: (1) we found a very strong genetic
      divergence between wild sea beet and other relatives, which was unexpected given
      the recent evolutionary history and the full cross-compatibility of all taxa and
      (2) we definitely confirmed that the classification into cultivated, wild,
      ruderal and weed forms according to their geographical location, phenotype or
      their domesticated status is clearly in accordance with genetic clustering
      despite the very recent domestication process of sugar beet.

PMID- 18335203
TI  - QTL for phytosterol and sinapate ester content in Brassica napus L. collocate
      with the two erucic acid genes.
AB  - Improving oil and protein quality for food and feed purposes is an important goal
      in rapeseed (Brassica napus L.) breeding programs. Rapeseed contains
      phytosterols, used to enrich food products, and sinapate esters, which are
      limiting the utilization of rapeseed proteins in the feed industry. Increasing
      the phytosterol content of oil and lowering sinapate ester content of meal could
      increase the value of the oilseed rape crop. The objective of the present study
      was to identify quantitative trait loci (QTL) for phytosterol and sinapate ester
      content in a winter rapeseed population of 148 doubled haploid lines, previously
      found to have a large variation for these two traits. This population also
      segregated for the two erucic acid genes. A close negative correlation was found
      between erucic acid and phytosterol content (Spearman's rank correlation, r(s) = 
      0.80**). For total phytosterol content, three QTL were detected, explaining 60%
      of the genetic variance. The two QTL with the strongest additive effects were
      mapped on linkage groups N8 and N13 within the confidence intervals of the two
      erucic acid genes. For sinapate ester content four QTL were detected, explaining
      53% of the genetic variance. Again, a close negative correlation was found
      between erucic acid and sinapate ester content (r(s) = -0.66**) and the QTL with
      the strongest additive effects mapped on linkage groups N8 and N13 within the
      confidence intervals of the two erucic acid genes. The results suggests, that
      there is a pleiotropic effect of the two erucic acid genes on phytosterol and
      sinapate ester content; the effect of the alleles for low erucic acid content is
      to increase phytosterol and sinapate ester content. Possible reasons for this are
      discussed based on known biosynthetic pathways.

PMID- 18335204
TI  - A Kir6.2 mutation causing severe functional effects in vitro produces neonatal
      diabetes without the expected neurological complications.
AB  - AIMS/HYPOTHESIS: Heterozygous activating mutations in the pancreatic ATP
      sensitive K+ channel cause permanent neonatal diabetes mellitus (PNDM). This
      results from a decrease in the ability of ATP to close the channel, which thereby
      suppresses insulin secretion. PNDM mutations that cause a severe reduction in ATP
      inhibition may produce additional symptoms such as developmental delay and
      epilepsy. We identified a heterozygous mutation (L164P) in the pore-forming
      (Kir6.2) subunit of the channel in three unrelated patients and examined its
      functional effects. METHODS: The patients (currently aged 2, 8 and 20 years)
      developed diabetes shortly after birth. The two younger patients attempted
      transfer to sulfonylurea therapy but were unsuccessful (up to 1.1 mg kg(-1) day(
      1)). They remain insulin dependent. None of the patients displayed neurological
      symptoms. Functional properties of wild-type and mutant channels were examined by
      electrophysiology in Xenopus oocytes. RESULTS: Heterozygous (het) and homozygous
      L164P K(ATP) channels showed a marked reduction in channel inhibition by ATP.
      Consistent with its predicted location within the pore, L164P enhanced the
      channel open state, which explains the reduction in ATP sensitivity. HetL164P
      currents exhibited greatly increased whole-cell currents that were unaffected by
      sulfonylureas. This explains the inability of sulfonylureas to ameliorate the
      diabetes of affected patients. CONCLUSIONS/INTERPRETATION: Our results provide
      the first demonstration that mutations such as L164P, which produce a severe
      reduction in ATP sensitivity, do not inevitably cause developmental delay or
      neurological problems. However, the neonatal diabetes of these patients is
      unresponsive to sulfonylurea therapy. Functional analysis of PNDM mutations can
      predict the sulfonylurea response.

PMID- 18335205
TI  - [Total knee arthroplasty - GPs' views in Germany: a questionnaire-based study].
AB  - To assess general knowledge and individual views of general practitioners (GPs)
      on total knee arthroplasty (TKA), we conducted a questionnaire-based survey
      involving 170 GPs in Germany. Eighty-one GPs returned the questionnaire. They
      treat a mean of 10.6+/-8.3 patients with TKA. General knowledge can be estimated
      as good. Compared with the data in the literature, GPs assessed the rate of
      satisfied patients as lower and the risk for revision surgery as higher. The mean
      risk of potential complications (infection, instability, persistent pain) in
      association with TKA was estimated correctly. Seventy-eight percent of GPs
      consider an allergic reaction to the implant or bone cement as problematic. The
      number of cases per year, personal experience with the surgeon, and - less
      important - local accessibility are important factors for GPs when recommending
      an operating centre to a patient.A broad spectrum of individual responses
      indicates the need to improve the information transfer between orthopaedic
      surgeons and referring GPs.

PMID- 18335206
TI  - Gastric diverticulum: a rare cause of hemorrhagic shock.

PMID- 18335207
TI  - Survival curve and factors related to drainage during the first 24 h after total
      knee arthroplasty.
AB  - Routine use of drains in total knee arthroplasty (TKA) is controversial. The aim
      of this study is to define the hourly risk of bleeding in the first 24 h
      following TKA using a survival study, to detect factors that might modify this
      risk, and establish a predictive model. In a retrospective study including 112
      knees, patients with a coagulation disorder, platelet disease, or anticoagulation
      treatment were excluded. The risk factors studied included anesthesia score of
      the American society of anesthesiologists (ASA), proteinemia, total volume of
      fluid drained, and the use of low molecular weight heparin. The Kaplan-Meier
      test, Mantel-Haenszel test, and Cox regression analysis were used for the
      statistical calculations. The results indicate that the drains used in TKA can be
      removed within the first 18 h with a high degree of safety and low risk of
      persistent bleeding. The evolution of postoperative bleeding was independent of
      the factors studied.

PMID- 18335208
TI  - Chondrolysis after partial lateral meniscectomy in athletes.
AB  - Rapid chondrolysis after partial arthroscopic lateral meniscectomy has been
      seldom reported in literature. Considering the relatively high number of partial
      lateral meniscectomy performed, we cannot understand why this complication is so
      rare. The purpose of this paper is to report a series of athletes developing a
      chondrolysis associated with posterolateral corner laxity after a partial lateral
      meniscectomy and attempt to hypothesize the pathogenesis of this devastating
      complication. Five male professional soccer players of Italian championship with
      a mean age of 26.8 years underwent a partial lateral meniscectomy because of a
      traumatic lateral meniscus tear. Patients showed a slight varus knee and there
      were clinical signs compatible with a meniscal tear. No other pathological sign
      were found. An MRI scan confirmed these findings. After surgery patients were
      unable to resume sport activities because of swelling and knee pain during
      training sessions. At a mean time of 8 months (range 6-12 months) from surgery
      patients were re-examined and a new MRI scan was performed. Clinical examination
      revealed a slight swelling of the knee and signs of posterolateral corner laxity.
      MRI scan revealed intra-articular fluid and pathological findings of knee
      posterolateral corner associated with a thinning of the articular cartilage.
      Arthroscopy showed free cartilagineous debris floating into the knee and a high
      grade of cartilage damage on the lateral compartment. The evaluation of lateral
      compartment, ruled-out a new tear of the meniscal remnant and showed a positive
      drive-trough sign with knee in the Fig. 4 positioning. All patients had an open
      re-tensioning of the posterior meniscofemoral capsule, and in one case, an
      augmentation of the popliteal tendon using a free semi-tendinous graft was also
      done. This surgery gave a complete resolution of symptoms and patients resumed
      sports activities without any restriction after a period between 4 and 5 months.
      Based on this experience we hypothesize that partial lateral meniscectomy may
      have a role in causing a subtle rotatory instability that combined with high
      stress of sports activity can dramatically increase the susceptibility of joint
      to chondrolysis, Varus knee seems to be a possible predisposing factor. Open
      surgery addressing the insufficiency of lateral or posterolateral corner has been
      found to be effective in improving knee function and resolve patients symptoms at
      a short-term follow-up.

PMID- 18335209
TI  - Feasibility of using solid sampling graphite furnace atomic absorption
      spectrometry for preparation of spiked filter papers with Cu and Zn as standards
      for direct solid analysis.
AB  - An approach was developed for the preparation of cryogenic ground spiked filter
      papers with Cu and Zn for use as synthetic calibrating standards for direct solid
      microanalysis. Solid sampling graphite furnace atomic absorption spectrometry was
      used to evaluate the microhomogeneity and to check the applicability of the
      synthetic calibrating standards for the direct determination of Cu and Zn in
      vegetable certified reference materials. The found concentrations presented no
      statistical differences at the 95% confidence level. The homogeneity factors
      ranged from 2.7 to 4.2 for Cu and from 6.4 to 11.5 for Zn.

PMID- 18335210
TI  - Novel application of modified multiwalled carbon nanotubes as a solid phase
      extraction adsorbent for the determination of polyhalogenated organic pollutants
      in aqueous solution.
AB  - This paper describes a novel application of pristine and chemically modified
      multiwalled carbon nanotubes (MWCNTs) as the packing materials for the
      determination of different polyhalogenated organic pollutants, pentachlorophenol,
      2,4,5-trichlorophenol, 3,3',4,4'-tetrachlorobiphenyl and 2,2',5,5'
      tetrabromobiphenyl, from aqueous solution based on solid phase extraction. The
      modified MWCNTs were characterized using different techniques and the results
      revealed the successful modification of the MWCNTs with octadecyl amine and
      poly(ethylene glycol), separately. Factors that maybe influence the
      preconcentration efficiency, such as sample flow rate, adsorbent mass, sample pH
      and sample volume, were studied. Desorption of the target analytes was studied
      using different solvents and the results showed that acetone was the best solvent
      for all the analytes compared with methanol and hexane. All the results indicated
      that the proposed method could be used for the simultaneous determination of
      different pollutants in environmental water samples at trace levels.

PMID- 18335211
TI  - Certification of methylmercury in cod fish tissue certified reference material by
      species-specific isotope dilution mass spectrometric analysis.
AB  - A new cod fish tissue certified reference material, NMIJ CRM 7402-a, for
      methylmercury analysis was certified by the National Metrological Institute of
      Japan in the National Institute of Advanced Industrial Science and Technology
      (NMIJ/AIST). Cod fish was collected from the sea close to Japan. The cod muscle
      was powdered by freeze-pulverization and was placed into 600 glass bottles (10 g
      each), which were sterilized with gamma-ray irradiation. The certification was
      carried out using species-specific isotope dilution gas chromatography
      inductively coupled plasma mass spectrometry (SSID-GC-ICPMS), where (202)Hg
      enriched methylmercury (MeHg) was used as the spike compound. In order to avoid
      any possible analytical biases caused by nonquantitative extraction, degradation
      and/or formation of MeHg in sample preparations, two different extraction methods
      (KOH/methanol and HCl/methanol extractions) were performed, and one of these
      extraction methods utilized two different derivatization methods (ethylation and
      phenylation). A double ID method was adopted to minimize the uncertainty arising
      from the analyses. In order to ensure not only the reliability of the analytical
      results but also traceability to SI units, the standard solution of MeHg used for
      the reverse-ID was prepared from high-purity MeHg chloride and was carefully
      assayed as follows: the total mercury was determined by ID-ICPMS following aqua
      regia digestion, and the ratio of Hg as MeHg to the total Hg content was
      estimated by GC-ICPMS. The certified value given for MeHg is 0.58 +/- 0.02 mg kg(
      1) as Hg.

PMID- 18335212
TI  - Electroanalytical performance of a terbium(III)-selective sensor based on a
      neutral ionophore in environmental and medicinal samples.
AB  - A new highly selective terbium(III) electrode was prepared with a polymeric film
      doped using S-2-benzothiazolyl-2-amino-alpha-(methoxyimino)-4-thiazolethiol
      acetate as an electroactive material, benzyl acetate (BA) as a plasticizer, and
      potassium tetrakis(4-chlorophenyl) borate (KTpClPB) as an anionic site in the
      percentage ratio 3.17:1.58:63.4:31.7 (ionophore-KTpClPB-BA-PVC, w/w). The
      electrode exhibited a linear response with a near Nernstian slope of 19.5
      mV/decade within the concentration range 1.5 x 10(-7)-1.0 x 10(-2) M terbium
      ions, with a working pH range from 2.0 to 8.0, and a fast response time of 10 s
      and presented satisfactory reproducibility. The limit of detection was 9.3 x 10(
      8) M. The results show that this electrode can be used in ethanol media up to 30%
      (v/v) concentration without interference. It can be used for 3 months without any
      considerable divergence in the potentials. Selectivity coefficients for
      terbium(III) with respect to many cations were investigated. The electrode is
      highly selective for terbium(III) ions over a large number of monovalent,
      bivalent, and trivalent cations. This shows the valuable property of the proposed
      electrode. The stability constant of the ionophore towards Tb(3+) ions was
      determined with the sandwich membrane method. It was successfully used as an
      indicator electrode in potentiometric determination of terbium(III) ions with
      EDTA and in direct determination in tap water and binary mixtures with
      quantitative results. The utility of the proposed electrode was also determined
      in the presence of ionic and nonionic surfactants and in the presence of fluoride
      ions in four pharmaceutical (mouthwash) preparations. [figure: see text]

PMID- 18335213
TI  - Microtechnologies for membrane protein studies.
AB  - Despite the rapid and enormous progress in biotechnologies, the biochemical
      analysis of membrane proteins is still a difficult task. The presence of the
      large hydrophobic region buried in the lipid bilayer membrane (transmembrane
      domain) makes it difficult to analyze membrane proteins in standard assays
      developed for water-soluble proteins. To handle membrane proteins, the lipid
      bilayer membrane may be used as a platform to sustain their functionalities.
      Relatively slow progress in developing micro total analysis systems (microTAS)
      for membrane protein analysis directly reflects the difficulty of handling lipid
      membranes, which is a common problem in bulk measurement technologies.
      Nonetheless, researchers are continuing to develop efficient and sensitive
      analytical microsystems for the study of membrane proteins. Here, we review the
      latest developments, which enable detection of events caused by membrane
      proteins, such as ion channel current, membrane transport, and receptor/ligand
      interaction, by utilizing microfabricated structures. High-throughput and highly
      sensitive detection systems for membrane proteins are now becoming a realistic
      goal. Although most of these systems are still in the early stages of
      development, we believe this field will become one of the most important
      applications of microTAS for pharmaceutical and clinical screenings as well as
      for basic biochemical research.

PMID- 18335214
TI  - Recent advances in electric analysis of cells in microfluidic systems.
AB  - Microfluidics offers an ideal platform to integrate cell-based assays with
      electric measurements. The technological advances in microfluidics,
      microelectronics, electrochemistry, and electrophysiology have greatly inspired
      the development of microfluidic/electric devices that work with a low number of
      cells or single cells. The applications of these microfluidic systems range from
      the detecting of cell culture density to the probing of cellular functions at the
      single-cell level. In this review, we introduce the recent advances in the
      electric analysis of cells on a microfluidic platform, specifically related to
      the quantification and monitoring of cells in static solution, on-chip patch
      clamp measurement, and examination of flowing cells. We also point out future
      directions and challenges in this field.

PMID- 18335215
TI  - Lichens biomonitoring as feasible methodology to assess air pollution in natural
      ecosystems: combined study of quantitative PAHs analyses and lichen biodiversity
      in the Pyrenees Mountains.
AB  - The air quality in the Aragon valley, in the central Pyrenees, has been assessed
      by evaluation of lichen biodiversity and mapped by elaboration of the Index of
      Air Purity (IAP) based on observations of the presence and abundance of eight
      kinds of lichen with different sensitivity to air pollution. The IAP values
      obtained have been compared with quantitative analytical measures of 16 PAHs in
      the lichen Evernia prunastri, because this species was associated with a wide
      range of traffic exposure and levels of urbanization. Analyses of PAHs were
      carried out by the DSASE method followed by an SPE clean-up step and GC-MS
      analysis. The concentration of total PAHs found in lichen samples from the Aragon
      valley ranged from 692 to 6420 ng g(-1) and the PAHs profile showed predominance
      of compounds with three aromatic rings. The influence of the road traffic in the
      area has been shown because values over the median concentration of PAHs (>1092
      ng g(-1)), percentage of combustion PAHs (>50%), and equivalent toxicity (>169)
      were found in lichens collected at places exposed to the influence of traffic.
      The combination of both methods suggests IAP as a general method for evaluating
      the air pollution referenced to PAHs because it can be correlated with the
      content of combustion PAHs and poor lichen biodiversity can be partly explained
      by the air pollution caused by specific PAHs.

PMID- 18335216
TI  - Protein engineering of hydrogenase 3 to enhance hydrogen production.
AB  - The large subunit (HycE, 569 amino acids) of Escherichia coli hydrogenase 3
      produces hydrogen from formate via its Ni-Fe-binding site. In this paper, we
      engineered HycE for enhanced hydrogen production by an error-prone polymerase
      chain reaction (epPCR) using a host that lacked hydrogenase activity via the hyaB
      hybC hycE mutations. Seven enhanced HycE variants were obtained with a novel
      chemochromic membrane screen that directly detected hydrogen from individual
      colonies. The best epPCR variant contained eight mutations (S2T, Y50F, I171T,
      A291V, T366S, V433L, M444I, and L523Q) and had 17-fold higher hydrogen-producing
      activity than wild-type HycE. In addition, this variant had eightfold higher
      hydrogen yield from formate compared to wild-type HycE. Deoxyribonucleic acid
      shuffling using the three most-active HycE variants created a variant that has 23
      fold higher hydrogen production and ninefold higher yield on formate due to a 74
      amino acid carboxy-terminal truncation. Saturation mutagenesis at T366 of HycE
      also led to increased hydrogen production via a truncation at this position;
      hence, 204 amino acids at the carboxy terminus may be deleted to increase
      hydrogen production by 30-fold. This is the first random protein engineering of a
      hydrogenase.

PMID- 18335217
TI  - Quantification of dopaminergic neurotransmission SPECT studies with 123I-labelled
      radioligands. A comparison between different imaging systems and data acquisition
      protocols using Monte Carlo simulation.
AB  - PURPOSE: (123)I-labelled radioligands are commonly used for single-photon
      emission computed tomography (SPECT) imaging of the dopaminergic system to study
      the dopamine transporter binding. The aim of this work was to compare the
      quantitative capabilities of two different SPECT systems through Monte Carlo (MC)
      simulation. METHODS: The SimSET MC code was employed to generate simulated
      projections of a numerical phantom for two gamma cameras equipped with a parallel
      and a fan-beam collimator, respectively. A fully 3D iterative reconstruction
      algorithm was used to compensate for attenuation, the spatially variant point
      spread function (PSF) and scatter. A post-reconstruction partial volume effect
      (PVE) compensation was also developed. RESULTS: For both systems, the correction
      for all degradations and PVE compensation resulted in recovery factors of the
      theoretical specific uptake ratio (SUR) close to 100%. For a SUR value of 4, the
      recovered SUR for the parallel imaging system was 33% for a reconstruction
      without corrections (OSEM), 45% for a reconstruction with attenuation correction
      (OSEM-A), 56% for a 3D reconstruction with attenuation and PSF corrections (OSEM
      AP), 68% for OSEM-AP with scatter correction (OSEM-APS) and 97% for OSEM-APS plus
      PVE compensation (OSEM-APSV). For the fan-beam imaging system, the recovered SUR
      was 41% without corrections, 55% for OSEM-A, 65% for OSEM-AP, 75% for OSEM-APS
      and 102% for OSEM-APSV. CONCLUSION: Our findings indicate that the correction for
      degradations increases the quantification accuracy, with PVE compensation playing
      a major role in the SUR quantification. The proposed methodology allows us to
      reach similar SUR values for different SPECT systems, thereby allowing a reliable
      standardisation in multicentric studies.

PMID- 18335218
TI  - Bisphosphonates induce apoptosis in CLL cells independently of MDR phenotype.
AB  - PURPOSE: The anti-tumoral activity of bisphosphonates (BPs) has been reported in
      leukemia. In this study, we attempted to evaluate the apoptotic effects of the
      BPs pamidronate (PAM) and zoledronic acid (ZOL) in chronic lymphocytic leukemia
      (CLL) samples, and to correlate it with clinical parameters and multidrug
      resistance (MDR) phenotype (P-glycoprotein and multidrug resistance-related
      protein expression and/or their functional activity). RESULTS: Both BPs were able
      to induce apoptosis significantly. No correlation was observed between BP-induced
      apoptosis and clinical parameters or MDR phenotype. CONCLUSION: Our data suggest
      that concurrent or sequential administration of BPs with conventional
      chemotherapeutic drugs may have significant therapeutic potential for CLL
      patients.

PMID- 18335219
TI  - Cisplatin plus weekly CPT-11/docetaxel in advanced esophagogastric cancer: a
      phase I study with pharmacogenetic assessment of XPD, XRCC3 and UGT1A1
      polymorphisms.
AB  - PURPOSE: A multicenter phase I trial to establish the recommended dose of CPT
      11/docetaxel plus cisplatin in advanced esophagogastric cancer patients and to
      correlate the efficacy and toxicity with genetic polymorphisms in DNA repair
      genes (XPD and XRCC3) and the UGT1A1 gene. METHODS: Four dose levels with a fixed
      dose of cisplatin (60 mg/m(2)), day 1, and dose-escalation of CPT-11 (50-70
      mg/m(2)) and docetaxel (25-30 mg/m(2)), days 1 and 8, every 3 weeks were planned.
      Polymorphisms of XPD (Asp312Asn and Lys751Gln), XRCC3 (Thr241Met) and UGT1A1*28
      were examined in baseline peripheral blood. RESULTS: Twenty-eight patients were
      included at three different dose levels. Dose-limiting toxicities were febrile
      neutropenia and diarrhea; the recommended dose was established at CPT-11 60
      mg/m(2) and docetaxel 25 mg/m(2) plus cisplatin 60 mg/m(2). Objective response
      was observed in 13 patients (50%). Median time to progression was 6.6 months, and
      median survival was 11.3 months. Median time to progression was 9.7 months for
      patients harboring the XRCC3 Met241Met genotype versus 8.4 months for patients
      with Thr241Met and 3.1 months for those with Thr241Thr (P = .04). CONCLUSIONS:
      CPT-11/docetaxel plus cisplatin is active in patients with advanced
      esophagogastric cancer. XRCC3 Met241Thr polymorphisms could be a useful marker to
      predict prognosis in patients treated with a cisplatin-based chemotherapy.
      However, these results are required to be confirmed with a great number of
      patients.

PMID- 18335220
TI  - Leukocytapheresis for the treatment of refractory Henoch-Schonlein purpura
      resistant to both prednisolone and intravenous immunoglobulin therapy.

PMID- 18335221
TI  - Radical prostatectomy for high-risk prostate cancer.
AB  - OBJECTIVES: Consensus recommendations for the identification and treatment of men
      whose apparent organ confined prostate cancer has high risk features are lacking.
      Despite ongoing refinements in surgical technique and improvements in morbidity
      and functional outcomes, the tradition of steering high-risk patients away from
      radical prostatectomy (RP) remains steadfast. METHODS: We performed a medical
      literature search in English using MEDLINE/PubMed that addressed high risk
      prostate cancer. We analyzed the literature with respect to the historical
      evolution of this concept, current risk stratification schemes and treatment
      guidelines and related short and long term outcomes following RP. RESULTS:
      Contemporary evidence suggest that patients classified with high-risk prostate
      cancer by commonly used definitions do not have a uniformly poor prognosis after
      RP. Many cancers categorized clinically as high risk are actually pathologically
      confined to the prostate, and most men with such cancers who undergo RP are alive
      and free of additional therapy long after surgery. RP in the high-risk setting
      appears to be associated with a similar morbidity as in lower-risk patients.
      CONCLUSION: Men with clinically localized high-risk prostate cancer should not be
      categorically disqualified from local definitive therapy with RP. With careful
      attention to surgical technique, cancer control rates should improve further, and
      adverse effects on quality of life after RP should continue to decrease.

PMID- 18335222
TI  - Tumor vaccines in renal cell carcinoma.
AB  - INTRODUCTION: Although most vaccines target foreign infectious agents,
      therapeutic cancer vaccines target both well-established and metastatic tumor
      cells expressing tumor antigens. Active immunotherapy is intended to enhance or
      activate the immunosurveillance of an individual through a therapeutic vaccine.
      Renal cell carcinoma (RCC) is one of the most immunoresponsive cancers in humans,
      which in turn makes it an ideal candidate for immune based therapies. METHOD:
      Several types of therapeutic vaccines have been tested and applied in the
      clinical setting and can be divided into cell-based vaccines including direct
      application of inactivated autologous tumor cells, gene modified tumor cell
      based, dendritic cell-based (expressing RCC derived tumor antigens), and non-cell
      based vaccines. This review will examine the current status of cell-based vaccine
      immunotherapy and focuses on non-cell-based vaccine strategies. CONCLUSION:
      Recent advances in molecular targeting therapy have introduced a battery receptor
      tyrosine kinase (RTK) and mTOR inhibitors that provide promising treatment
      options, however, the tolerability of tumor vaccines and the success of clinical
      effectiveness in selected populations combined with recent advances in cellular
      therapies warrant the continued exploration of novel methods of tumor vaccine
      therapies in the clinical setting.

PMID- 18335225
TI  - Intestinal evisceration through the anus caused by fragile rectal wall.

PMID- 18335224
TI  - Activity of paclitaxel in metastatic squamous anal carcinoma.

PMID- 18335223
TI  - [Mucous membrane pemphigoid with ocular involvement. Part I: Clinical
      manifestations, pathogenesis and diagnosis].
AB  - Mucous membrane pemphigoid is a subepidermal blistering autoimmune disorder
      characterized by predominant involvement of mucous membranes and the presence of
      autoantibodies against proteins of the dermal-epidermal junction. Lesions most
      frequently develop in the oral cavity followed, in descending order of frequency,
      by conjunctiva, nasopharynx, the anogenital region, skin, larynx, and oesophagus.
      When the lesions are restricted to the conjunctiva, the term ocular pemphigoid
      may be applied. Cicatrization of the plica is considered a pathognomonic sign in
      early disease. Recurrent conjunctival inflammation results in subepithelial
      fibrosis, which leads to fornix shortening, symblepharon formation and subsequent
      trichiasis and entropion. Even in the absence of conjunctival inflammation,
      ankyloblepharon may occur. In end stage disease, limbal stem cell deficiency,
      tear deficiency, and lid malpositions may occur and result in a total
      keratinization of the ocular surface. The diagnosis is based on clinical findings
      and the detection of linear deposits of IgG and/or IgA and/or C3 at the dermal
      epidermal junction by direct immunofluorescence microscopy of a perilesional
      biopsy. Autoantibodies (against type XVII and VII collagen, laminin 5 and 6,
      alpha6beta4 integrin, BP230) have been detected in patient serum. In the case of
      ocular involvement, preferential reactivity against beta4 integrin has been
      described.

PMID- 18335226
TI  - Comparison of multiple dose GnRH antagonist and minidose long agonist protocols
      in poor responders undergoing in vitro fertilization: a randomized controlled
      trial.
AB  - OBJECTIVE: To investigate the efficacy of gonadotropin releasing hormone
      antagonist (GnRH) in poor responders undergoing in vitro fertilization. STUDY
      DESIGN: Ninety-six patients with poor ovarian response in previous treatment
      cycles were prospectively randomized into two groups. Forty-four patients were
      stimulated with GnRH antagonist multidose protocol and 45 patients received a
      standard long agonist protocol. Ovarian response was evaluated by transvaginal
      ultrasound and hormonal parameters. Cycle characteristics and treatment outcomes
      were statistically compared between groups. RESULTS: There was significantly
      reduced duration of stimulation and consumption of gonadotrophins in the
      antagonist group when compared to the agonist group. The estradiol concentrations
      on the day of human chorionic gonadotropin (hCG) injection, the number of oocytes
      retrieved, and the number of embryos transferred were similar for both groups. In
      the antagonist group, eight (18.1%) ongoing pregnancies were achieved and in the
      agonist group, ten (22.2%) clinical pregnancies were achieved but the difference
      was not statistically significant. CONCLUSION: The present study was not powered
      to detect clinically relevant differences between two protocols in outcomes such
      as pregnancy rate, with confidence.

PMID- 18335227
TI  - Juvenile cystic adenomyosis mimicking uterine malformation: a case report.
AB  - Cystic adenomyosis is a rare form of adenomyosis mostly seen in middle aged
      women. We report a case of cystic adenomyosis in a juvenile patient presenting
      with severe dysmenorrhea refractory to any given medication. The patient
      initially was diagnosed as uterus bicornis with an obstructed rudimentary horn.
      Surgical exploration and excision of the cystic mass relieved the symptoms of the
      patient.

PMID- 18335228
TI  - An unusual presentation of endometrial cancer: a case report and literature
      review.
AB  - BACKGROUND: The purpose of this case report is to describe the failure of
      standard diagnostic work up in the presence of an advanced stage endometrial
      cancer and briefly review the literature about the efficacy of the currently
      utilized diagnostic tools in the evaluation of women with postmenopausal bleeding
      (PMB). CASE: A 71-year-old normal weight lady presented with an unprovoked PMB.
      Initial evaluation consisted of pelvic ultrasound followed by office hysteroscopy
      and directed endometrial biopsy. Biopsy was negative but her symptom persisted,
      so she had a repeat hysteroscopy with dilatation and curettage (D&C) in the
      operating room. The D&C histology was again negative but elevated CA 125 and a
      suspicious looking intramural "fibroid" on ultrasound and MRI prompted our advice
      for hysterectomy. At the time of surgery, a stage III C endometrial cancer was
      found. CONCLUSION: A high level of vigilance is required in the evaluation of
      women presenting with symptoms suspicious for endometrial cancer. When these
      symptoms persist despite negative initial work up, continuing evaluation and
      sometimes intervention are required on the part of the clinician.

PMID- 18335229
TI  - Impact of hormone replacement therapy on the histologic subtype of breast cancer.
AB  - OBJECTIVE: Postmenopausal hormone replacement therapy (HRT) is associated with an
      increase in breast cancer risk, which correlates to the duration of HRT use. We
      wanted to investigate a possible association between HRT use and the risk of a
      histologic subtype of breast cancer. PATIENTS AND METHODS: From 1995 until 2004,
      497 cases of primary ductal, lobular or ductulolobular breast cancer in
      postmenopausal women were diagnosed at the Department of Gynecology and
      Obstetrics, University Hospital Basel, Switzerland. The data was derived from
      patient's records. HRT ever use was defined as HRT use for > or =6 months.
      RESULTS: Of the 99 cases of lobular cancer 72.7% were invasive lobular cancers,
      21.2% were invasive ductulolobular cancers and 6.1% were lobular cancers in situ.
      Of the 398 cases of ductal cancer, 90.5% were invasive ductal cancers and 9.5%
      were ductal cancers in situ. Totally 144 women were HRT ever users, and 341 women
      were HRT never users. HRT status could not be defined in 12 women. HRT ever use
      was associated with an increased risk for lobular cancer (OR 1.67; 95% CI 1.02
      2.73). Also, menopause due to bilateral oophorectomy was associated with an
      increased risk for lobular cancer (OR 2.42; 95% CI 1.06-5.54). CONCLUSIONS: There
      is evidence that HRT as well as menopause due to bilateral oophorectomy may be
      associated with an increased risk for lobular cancer. This association is of
      major clinical relevance, since lobular breast cancer is more difficult to
      diagnose clinically and radiologically than ductal breast cancer.

PMID- 18335231
TI  - Anesthesia machine as a cause of intraoperative "code red" in the labor and
      delivery suite.
AB  - Fire is a rare but potentially disastrous operating room misadventure. I herein
      describe the first reported case of a fire in the labor and delivery suite, which
      also happens to be the first case of a fire caused by malfunctioning anesthesia
      machine.

PMID- 18335230
TI  - Vulvar pilonidal sinuses: treatment of a rare cause of vulvar pain.
AB  - It is hoped that if cases of vulvar pilonidal sinus (PS) are known to readers of
      this article, they will be called to the writer's attention and that further
      studies of the origin and cause of these anterior pathologic developments will
      result. A delay in diagnosis and treatment of this relatively harmless condition
      can lead to complications like abscess formation. Early diagnosis, complete
      excision and elimination of the anatomical factor that cause accumulation of hair
      fragments are followed by an excellent prognosis.

PMID- 18335232
TI  - Mre11 nuclease and C-terminal tail-mediated DDR functions are required for
      initiating yeast telomere healing.
AB  - Mre11 is a central factor in creating an optimal substrate for telomerase loading
      and elongation. We have used a G2/M synchronized telomere-healing assay as a tool
      to separate different functions of Mre11 that are not apparent in null alleles.
      An analysis of healing efficiencies of several mre11 alleles revealed that both
      nuclease and C-terminal mutations led to a loss of healing. Interestingly, trans
      complementation of the 49 amino acid C-terminal deletion (DeltaC49) and the D16A
      mutant, deficient in nuclease activity and partially defective in MRX complex
      formation, restores healing. DeltaC49 provokes Rad53 phosphorylation after
      treatment with the radiomimetic agent MMS exclusively through the Tel1 pathway,
      suggesting that a Tel1-mediated function is initiated through the C-terminal
      tail.

PMID- 18335233
TI  - Ultra-high-resolution dual-source CT for forensic dental visualization
      discrimination of ceramic and composite fillings.
AB  - Dental identification is the most valuable method to identify human remains in
      single cases with major postmortem alterations as well as in mass casualties
      because of its practicability and demanding reliability. Computed tomography (CT)
      has been investigated as a supportive tool for forensic identification and has
      proven to be valuable. It can also scan the dentition of a deceased within
      minutes. In the present study, we investigated currently used restorative
      materials using ultra-high-resolution dual-source CT and the extended CT scale
      for the purpose of a color-encoded, in scale, and artifact-free visualization in
      3D volume rendering. In 122 human molars, 220 cavities with 2-, 3-, 4- and 5-mm
      diameter were prepared. With presently used filling materials (different
      composites, temporary filling materials, ceramic, and liner), these cavities were
      restored in six teeth for each material and cavity size (exception amalgam n =
      1). The teeth were CT scanned and images reconstructed using an extended CT
      scale. Filling materials were analyzed in terms of resulting Hounsfield units
      (HU) and filling size representation within the images. Varying restorative
      materials showed distinctively differing radiopacities allowing for CT-data-based
      discrimination. Particularly, ceramic and composite fillings could be
      differentiated. The HU values were used to generate an updated volume-rendering
      preset for postmortem extended CT scale data of the dentition to easily visualize
      the position of restorations, the shape (in scale), and the material used which
      is color encoded in 3D. The results provide the scientific background for the
      application of 3D volume rendering to visualize the human dentition for forensic
      identification purposes.

PMID- 18335234
TI  - Protective role of NHE-3 inhibition in rat renal transplantation undergoing acute
      rejection.
AB  - Acute rejection in renal transplantation disturbs solute and volume maintenance
      in humans accompanied by delayed graft function and poor prognosis. We recently
      reported that decreased expression and function of Na+/H+ exchanger type 3 (NHE
      3) in proximal tubules and epithelial Na+ channels and aquaporin 2 in collecting
      ducts are major mechanisms involved in Na+ and water imbalances shortly after
      transplantation in rat undergoing acute rejection. We performed kidney
      transplantations in rats with bilaterally nephrectomized recipients with acute
      rejection and, in addition, systemically administered a specific inhibitor of NHE
      3 (NHE-I). NHE inhibition in acute renal failure was shown to improve tubular
      function and recovery. The aim of this therapy was to reduce energy consumption
      of the graft and preserve NHE-3 function. Imbalances in electrolyte excretion
      declined in NHE-I-treated animals and NHE-3 activity was preserved. Observed NHE
      I-dependent changes in electrolyte excretion, polyuria, and reduced protein
      reabsorption in the acute postoperative phase are predictors of favorable graft
      outcome in humans.

PMID- 18335235
TI  - Enzymatic breakdown of raffinose oligosaccharides in pea seeds.
AB  - Both alkaline and acidic alpha-galactosidases (alpha-D: -galactoside
      galactohydrolases, E.C.3.2.1.22) isolated from various plant species have been
      described, although little is known about their co-occurrence and functions in
      germinating seeds. Here, we report on the isolation of two cDNAs, encoding for
      alpha-galactosidases from maturing and germinating seeds of Pisum sativum. One
      was identified as a member of the acidic alpha-galactosidase of the family 27
      glycosyl hydrolase cluster and the other as a member of the family of alkaline
      alpha-galactosidases, which are highly homologous to seed imbibition proteins
      (SIPs). PsGAL1 transcripts, encoding for the ACIDIC alpha-GALACTOSIDASE, were
      predominately expressed during seed maturation and acidic enzyme activities were
      already present in dry seeds, showing little changes during seed germination.
      Compartmentation studies revealed that acidic alpha-galactosidases were located
      in protein storage vacuoles (PSVs). PsAGA1, encoding for the ALKALINE alpha
      GALACTOSIDASE, was only expressed after radicle protrusion, when about 50% of
      RFOs have already been broken down. RFO breakdown was markedly decreased when the
      translation of the alkaline enzyme was inhibited, providing evidence that PsAGA1
      indeed functioned in RFO degradation. Based on these data, we present an
      integrated model of RFO breakdown by two sequentially active alpha-galactosidases
      in pea seeds.

PMID- 18335236
TI  - Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures.
AB  - Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid
      (SA), is a commonly used drug that has a dual role in animal organisms as an anti
      inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases
      (COXs), which catalyze prostaglandins production. It is known that ASA serves as
      an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme.
      Here, we provide evidences that ASA also behaves as an agent inducing programmed
      cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a
      similar way than the well-established PCD-inducing agent H(2)O(2), although the
      induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA
      is herein shown to be a more efficient PCD-inducing agent than salicylic acid.
      ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and
      biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of
      mitochondrial membrane potential, cytochrome c release from mitochondria and
      induction of caspase-like activity. However, the ASA effect can be partially
      reverted by jasmonic acid. Taking together, these results reveal the existence of
      common features in ASA-induced animal apoptosis and plant PCD, and also suggest
      that there are similarities between the pathways of synthesis and function of
      prostanoid-like lipid mediators in animal and plant organisms.

PMID- 18335237
TI  - Helicobacter pylori-infection-associated CpG island hypermethylation in the
      stomach and its possible association with polycomb repressive marks.
AB  - Helicobacter pylori infection can induce CpG island (CGI) hypermethylation in
      gastric mucosa. Recently, genes occupied by Polycomb proteins in embryonic stem
      cells were shown to be vulnerable to aberrant DNA hypermethylation in cancers. To
      explore the relationship between H. pylori infection and DNA methylation changes
      in neoplastic and non-neoplastic stomach, we analyzed 25 CGIs and repetitive DNA
      elements from 82 chronic gastritis and 69 gastric carcinomas. Twenty-three CGIs
      showed significantly higher methylation levels in H. pylori-negative gastric
      carcinoma (n = 28) than in H. pylori-negative chronic gastritis (n = 39; P <
      0.05), indicating cancer-associated methylation. Eight CGIs exhibited
      significantly higher methylation levels in H. pylori-positive chronic gastritis
      (n = 43) than in H. pylori-negative chronic gastritis (n = 39; P < 0.05). Six
      CGIs showed both cancer-associated and H. pylori-associated hypermethylation. Six
      (75%) of the eight H. pylori-associated hypermethylated genes contained at least
      one of three repressive marks (Suzl2 occupancy, Eed occupancy, histone H3 K27
      trimethylation), whereas 31% of the remaining cancer-associated hypermethylated
      genes had at least one mark. The findings suggest that H. pylori infection
      strongly induces CGI hypermethylation in gastric epithelial cells and that
      susceptibility to H. pylori-induced DNA hypermethylation may be determined by
      Polycomb repressive marks in stem or progenitor cells.

PMID- 18335239
TI  - Clinical features and prognoses of 23 patients with chronic granulomatous disease
      followed for 21 years by a single hospital in Japan.
AB  - In this paper, we examined the details of severe infections, treatment
      efficacies, and the prognoses of 23 Japanese patients with chronic granulomatous
      disease (CGD). We described the mean ages at diagnosis and follow-up, which were
      2.8 years (range, 0.7-10 years) and 14.9 years (range, 0.2-28.4 years),
      respectively. There were three deaths, two from Aspergillus pneumonia and one
      from liver abscess. Eighteen of the 23 patients (78%) had a complete loss of
      gp91phox, and three had p22-phox and one had p67phox deficiencies. Aspergillus
      species were found in 45% of 174 severe infections. The mean height and weight of
      the 20 surviving patients were -0.8 +/- 1.3SD and -1.9 +/- 1.9SD below the means
      for age, respectively. Short stature and underweight (below the 10th percentile
      of the means) for age were seen in 22% and 17% of the patients, respectively.
      This growth retardation reflects the severity of the disease. At 20 years of age,
      there was 87% survival. Ongoing prophylaxis with trimethoprim-sulfamethoxazole
      (TMP-SMX) or antifungal drugs was given in 16 and 11 patients, respectively.
      Interferon-gamma (IFN-gamma) was given once a week to 14 patients. Four patients
      underwent hematopoietic stem cell transplantation (HSCT) and are currently well.
      There were infections observed in three of 21 identified related carriers of X
      linked CGD. A carrier with a liver abscess had 5% normal neutrophils during the
      acute phase of infection, which returned to 40% normal neutrophils after
      recovery. The high survival rate in this hospital results from regular follow-up
      and prophylaxis with TMP-SMX and anti-fungal drugs beginning at the time of
      diagnosis, along with treatment with weekly IFN-gamma.

PMID- 18335238
TI  - Outbreaks of human coronavirus in a pediatric and neonatal intensive care unit.
AB  - Human coronavirus 229E (HCoV) has been recently recognized as a potential agent
      of nosocomial viral respiratory infections (NRVI) in high-risk infants. We have
      confirmed this as fact through the study of a 1-year period of HCoV outbreaks
      occurring during a prospective survey of NRVI in a paediatric and neonatal
      intensive care unit (PNICU) using new molecular techniques for HCoV detection.
      Nasal samples obtained at admission and weekly thereafter for all hospitalised
      children, as well as monthly nasal samples from staff, were analysed using
      immunofluorescence for respiratory syncytial virus (RSV), influenza viruses A and
      B, paramyxoviruses 1, 2, 3 and adenoviruses. RT-PCR was used for HCoV detection.
      During the year 1998, 43 HCoV-related NRVI were detected in 152 neonates
      (incidence 28.3%), and 7 HCoV-related NRVI were found in 92 children (incidence
      7.6%). Three HCoV-related outbreaks were observed (February, August and
      December), associated with a high prevalence of HCoV infection in the staff.
      During the August outbreak, 50% to 78% of hospitalised neonates and children were
      infected. Seventy-five percent of hospitalised preterm neonates with a
      gestational age less than 32 weeks and 52.4% of staff members were infected. Risk
      factors for NRVI in neonates were birth weight, gestational age, ventilation,
      oxygenation and hospitalisation length. Ninety-two percent of infected preterm
      neonates were symptomatic, mainly with bradycardia and respiratory worsening.
      These data provide additional evidence for a possibly significant role of HCoV in
      NRVI in a PNICU. The role of staff or hospitalised children in spreading HCoV is
      hypothesised.

PMID- 18335240
TI  - Expression and localization of growth hormone and its receptors in the chicken
      ovary during sexual maturation.
AB  - Roles of pituitary growth hormone (GH) in female reproduction are well
      established. Autocrine and/or paracrine actions of GH in the mammalian ovary have
      additionally been proposed, although whether the ovary is an extra-pituitary site
      of GH expression in the laying hen is uncertain. This possibility has therefore
      been assessed in the ovaries of Hy-Line hens before (between 10-16 weeks of age)
      and after (week 17) the onset of egg laying. Reverse transcription/polymerase
      chain reaction (RT-PCR) analysis has consistently detected a full-length (690 bp)
      pituitary GH cDNA in ovarian stroma from 10 weeks of age, although GH expression
      is far lower than that in the pituitary gland or hypothalamus. GH mRNA is also
      present in small (>1-4 mm diameter) follicles after their ontogenetic appearance
      at 14 weeks of age and in all other developing follicles after 16 weeks of age
      (>4-30 mm diameter). Immunoreactivity for GH is similarly present in the ovarian
      stroma from 10 weeks of age and in small (<4 mm diameter) and large (>4-30 mm)
      follicles from 14 and 16 weeks of age, respectively. The relative intensity of GH
      staining in the ovarian follicles is consistently greater in the granulosa cells
      than in the thecal cells and is comparable with that in the follicular
      epithelium. A 321-bp fragment of GH receptor (GHR) cDNA, coding for the
      intracellular domain of the receptor, has also been detected by RT-PCR in the
      ovary and is present in stromal tissue by 10 weeks of age, in small follicles (<4
      mm diameter) by 14 weeks of age, and in larger follicles (>4-30 mm diameter) from
      16 weeks. GHR immunoreactivity has similarly been detected, like GH, in the
      developing ovary and in all follicles and is more intense in granulosa cells than
      in the theca interna or externa. The expression and location of the GH gene
      therefore parallels that of the GHR gene during ovarian development in the laying
      hen, as does the appearance of GH and GHR immunoreactivity. These results support
      the possibility that GH has autocrine and/or paracrine actions in ovarian
      function prior to and after the onset of lay in hens.

PMID- 18335241
TI  - Extracellular-regulated kinase activation regulates replication of Mycobacterium
      avium intracellularly in primary human monocytes.
AB  - Mycobacterium avium-intracellulare (MAI) is a ubiquitous environmental pathogen
      that causes disseminated infection in immunocompromised patients, such as those
      with human immunodeficiency virus, interleukin-12 deficiency, or interferon-gamma
      receptor mutation. Colony morphotypes are associated with MAI pathogenicity. Our
      previous studies have reported that smooth-transparent (SmT) morphotypes are more
      virulent and induce less cytokine (interleukin-1beta and tumor necrosis factor
      alpha) production by human monocytes than the smooth-domed (SmD) morphotypes.
      Mitogen-activated protein (MAP) kinases such as extracellular-regulated kinase
      (ERK) are activated by the phagocytosis of particle antigens in macrophages, and
      this ERK activation subsequently influences cytokine expression and the control
      of intracellular pathogen growth. The influence of MAP kinase activation on MAI
      replication in human monocytes was examined. Peripheral blood monocytes isolated
      from healthy subjects by Ficoll-Hypaque sedimentation were infected with virulent
      SmT or avirulent SmD MAI without or with MAP kinase inhibitors. MAP kinase
      activities were determined by in vitro kinase assay, intracellular MAI growth by
      CFU assay, and cytokines by enzyme-linked immunosorbent assay. MAI infection
      induced ERK and p38 activation. Inhibition of ERK by PD98059, but not p38,
      significantly increased intracellular MAI growth. Tumor necrosis factor-alpha
      release and interleukin-1beta production in response to MAI were reduced by MAP
      kinase inhibition. p38 inhibition tended to reduce cytokine production more
      substantially. These data suggest that ERK activation limits intra-monocytic MAI
      replication and enhances monocytic cytokine release, whereas p38 activation
      influences only cytokine release. The effect of MAP kinases on MAI growth might
      thus be mediated by the modulation of cytokine production.

PMID- 18335243
TI  - Survival, excitability, and transfection of retinal neurons in an organotypic
      culture of mature zebrafish retina.
AB  - Over the last 20 years, the zebrafish has become an important model organism for
      research on retinal function and development. Many retinal diseases do not become
      apparent until the later stages of life. This means that it is important to be
      able to analyze (gene) function in the mature retina. To meet this need, we have
      established an organotypic culture system of mature wild-type zebrafish retinas
      in order to observe changes in retinal morphology. Furthermore, cell survival
      during culture has been monitored by determining apoptosis in the tissue. The
      viability and excitability of ganglion cells have been tested at various time
      points in vitro by patch-clamp recordings, and retinal functionality has been
      assessed by measuring light-triggered potentials at the ganglion cell site. Since
      neurogenesis is persistent in adult zebrafish retinas, we have also monitored
      proliferating cells during culture by tracking their bromodeoxyuridine uptake.
      Reverse genetic approaches for probing the function of adult zebrafish retinas
      are not yet available. We have therefore established a rapid and convenient
      protocol for delivering plasmid DNA or oligonucleotides by electroporation to the
      retinal tissue in vitro. The organotypic culture of adult zebrafish retinas
      presented here provides a reproducible and convenient method for investigating
      the function of drugs and genes in the retina under well-defined conditions in
      vitro.

PMID- 18335242
TI  - Analysis of obstetric complications and uterine connective tissue in tenascin-X
      deficient humans and mice.
AB  - Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein.
      Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos
      syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS.
      EDS patients appear to have a higher risk of several complications during
      pregnancy, such as pelvic instability, premature rupture of membranes, and
      postpartum hemorrhage. Here, we present a study of genitourinary and obstetric
      complications in TNX-deficient women of reproductive age. We have found
      complications, such as uterus prolapses, that are in agreement with previous
      findings in other EDS types. In TNX knockout (KO) mice, we have observed mild
      pregnancy-related abnormalities. Morphological and immunohistological analysis of
      uterine tissues has not revealed obvious quantitative or spatial differences
      between TNX KO and wildtype mice with respect to collagen types I, III, V, and
      XII or elastic fibers. We conclude that TNX-deficient women are at risk of
      obstetric complications, but that TNX KO mice show only a mild phenotype.
      Furthermore, we show that TNX is involved in the stability of elastic fibers
      rather than in their initial deposition.

PMID- 18335245
TI  - Macrophage colony-stimulating factor is indispensable for repopulation and
      differentiation of Kupffer cells but not for splenic red pulp macrophages in
      osteopetrotic (op/op) mice after macrophage depletion.
AB  - We previously reported that macrophage colony-stimulating factor (M-CSF, CSF-1)
      played important roles in the process of the repopulation of Kupffer cells after
      their elimination by administration of liposome-entrapped dichloromethylene
      diphosphonate (lipo-MDP). In this study, we examined the repopulation of Kupffer
      cells and splenic red pulp macrophages in osteopetrotic (op/op) mice defective in
      the production of functional M-CSF and their littermate mice by using the lipo
      MDP model. In untreated op/op mice, numbers of F4/80-positive Kupffer cells in
      the liver and F4/80-positive splenic red pulp macrophages were reduced.
      Repopulation of Kupffer cells and splenic macrophages was observed in littermate
      (op/+) mice liver by 14 days after depletion. However, in op/op mice,
      repopulation of Kupffer cells was not observed in Kupffer-cell-depleted op/op
      mice until 56 days after depletion, whereas splenic red pulp macrophages
      repopulated and recovered to the level of control op/op mice by 10 days after
      depletion. Single injection of M-CSF was effective for the induction of the
      repopulation of Kupffer cells, and daily administration of M-CSF induced
      remarkable repopulation and maturation of Kupffer cells and proliferation of
      macrophage precursor cells in the liver of Kupffer-cell-depleted op/op mice.
      These results suggest that Kupffer cells are completely M-CSF-dependent tissue
      macrophages, whereas splenic red pulp macrophages are composed of M-CSF-dependent
      macrophages and M-CSF-independent macrophages. This mouse model provides a useful
      tool for the study of effects of growth factor on Kupffer cell differentiation in
      vivo.

PMID- 18335244
TI  - Early markers of regeneration following ductal ligation in rat submandibular
      gland.
AB  - Rat submandibular glands can recover their function and secretory protein content
      following ductal ligation-induced atrophy. Morphological studies have established
      that following ligation, deligation of the gland allows the regeneration of new
      salivary gland tissue. However, little is known about changes happening during
      early regeneration following intra-oral duct ligation, which does not damage the
      parasympathetic nerves. Glands that had been 2 weeks ligated or 2 weeks ligated +
      3 days deligated were compared. Tissue was prepared for histological,
      immunohistochemical (SMG-B and Ki-67) and immunocytochemical analyses (smooth
      muscle actin, aquaporin 5). Haematoxylin and eosin staining of deligated glands
      showed that some acini regained their cytoplasmic volume; moreover, the loss of
      Alcian blue/periodic acid-Schiff's staining from the lumen of ducts suggested
      successful deligation. The deligated gland was characterized by atypical acinar
      ductal branched structures, which were less frequent in the ligated gland and
      rarely seen in normal unoperated tissue. Myoepithelial cells were also
      investigated since changes in their morphology reflected changes in the acini
      morphology not readily detected by conventional staining. Actin staining revealed
      the presence of some shrunken acini in the atrophic tissue, whereas they had
      regained their normal morphology in the deligated gland suggesting that the acini
      were recovering. Some acini during deligation regained aquaporin 5 expression,
      which had decreased during atrophy. SMG-B protein, located in the pro-acinar cell
      during gland development and usually found in the intercalated duct cells in the
      adult, was detected in the newly formed acini of the deligated gland. This study
      suggests that morphological markers of regeneration appear as early as 3 days
      following ligation removal.

PMID- 18335246
TI  - Toxoneuron nigriceps parasitization delays midgut replacement in fifth-instar
      Heliothis virescens larvae.
AB  - We have analyzed the effects of Toxoneuron nigriceps parasitization on the midgut
      development of its host Heliothis virescens. In parasitized H. virescens larvae,
      the midgut epithelium undergoes a complete replacement, which is qualitatively
      not different to that observed in synchronous unparasitized larvae, with similar
      temporal profiles of cell death and metabolic activity. However, the whole gut
      replacement process is significantly delayed in parasitized larvae, with complete
      differentiation of the new gut epithelium being observed 4 days later than in
      unparasitized controls. The administration of juvenile hormone before commitment
      and of 20-hydroxyecdysone (20E) after commitment delays and fosters,
      respectively, the replacement process of the midgut epithelium; moreover, the
      injection of 20E into developmentally arrested and 20E-deficient host last-instar
      larvae parasitized by T. nigriceps immediately triggers regular gut development.
      These hormone-based experiments suggest that endocrine alterations in the larval
      host, induced by T. nigriceps parasitism, are responsible for the temporal
      alterations in the gut replacement process. The role of this parasitoid-induced
      developmental change in the host regulation process is discussed.

PMID- 18335248
TI  - Selection on spur shape in Impatiens capensis.
AB  - Rapid speciation within some plant families has been attributed to the evolution
      of floral spurs and to the effect of spur length on plant reproductive success.
      The flowers of Impatiens capensis (jewelweed) possess a long, curved spur in
      which nectar is produced and stored. Spur length and curvature varies among
      plants within one population. Here I document that spur shape is variable in
      natural populations, variation within plants is less than variation among plants,
      and spur shape is correlated with components of female and male reproductive
      success. The apparent natural selection is weakly directional in 1 of 2 years,
      with greatest seed production and pollen removal occurring in flowers with the
      greatest spur curvature. Bee pollinator visit length is longest at flowers with
      highly curved spurs, and they leave less nectar in these spurs than in flowers
      with straighter spurs. Spur angle evolution may be limited, at least in part, by
      opposing selection by nectar-robbers who prefer to visit flowers with greater
      spur curvature. Other factors that might contribute to the maintenance of spur
      angle variation are temporal variation in the strength of selection and potential
      genetic correlations of spur shape with other traits under selection.

PMID- 18335247
TI  - Involvement of growth hormone-insulin-like growth factor I system in cranial
      remodeling during halibut metamorphosis as indicated by tissue- and stage
      specific receptor gene expression and the presence of growth hormone receptor
      protein.
AB  - The role of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the
      tissue remodeling associated with the transition of a symmetrical larva to an
      asymmetrical juvenile during flatfish metamorphosis is unknown. In order to
      investigate the potential role of these hormones in the remodeling of cranial
      bone and soft tissue that accompanies eye migration during metamorphosis of
      Atlantic halibut (Hippoglossus hippoglossus) larvae, tissue-specific gene
      expression was monitored by in situ hybridization for Atlantic halibut type I
      growth hormone receptor (hhGHR), type II hhGHR, and insulin-like growth factor-I
      receptor (hhIGF-IR). Polyclonal antibody generated against the extracellular
      domain of type I hhGHR was used for the immunohistochemical localization of type
      I GHR protein. Type I hhGHR, type II hhGHR, and hhIGF-IR mRNA were expressed in
      fibroblasts, frontal bone osteocytes, and dorsal chondrocytes at the onset of
      metamorphosis (stage 8), during metamorphic climax (stage 9), and in fully
      metamorphosed juveniles (stage 10). Type I GHR protein showed similar expression
      patterns to those of type I hhGHR mRNA, except in chondrocytes in which little
      GHR protein was detected. The localization of GHR and IGF-IR transcripts and GHR
      protein in cranial structures that undergo remodeling is intriguing and suggests
      that, in addition to thyroid hormones, the GH-IGF-I system is involved in
      morphological transformations during metamorphosis in Atlantic halibut.

PMID- 18335249
TI  - Small and large wetland fragments are equally suited breeding sites for a ground
      nesting passerine.
AB  - Large habitat fragments are generally thought to host more species and to offer
      more diverse and/or better quality habitats than small fragments. However, the
      importance of small fragments for population dynamics in general and for
      reproductive performance in particular is highly controversial. Using an
      information-theoretic approach, we examined reproductive performance and
      probability of local recruitment of color-banded reed buntings Emberiza
      schoeniclus in relation to the size of 18 wetland fragments in northeastern
      Switzerland over 4 years. We also investigated if reproductive performance and
      recruitment probability were density-dependent. None of the four measures of
      reproductive performance (laying date, nest failure probability, fledgling
      production per territory, fledgling condition) nor recruitment probability were
      found to be related to wetland fragment size. In terms of fledgling production,
      however, fragment size interacted with year, indicating that small fragments were
      better reproductive grounds in some years than large fragments. Reproductive
      performance and recruitment probability were not density-dependent. Our results
      suggest that small fragments are equally suited as breeding grounds for the reed
      bunting as large fragments and should therefore be managed to provide a habitat
      for this and other specialists occurring in the same habitat. Moreover, large
      fragments may represent sinks in specific years because a substantial percentage
      of all breeding pairs in our study area breed in large fragments, and
      reproductive failure in these fragments due to the regularly occurring floods may
      have a much stronger impact on regional population dynamics than comparable
      events in small fragments.

PMID- 18335250
TI  - Swan foraging shapes spatial distribution of two submerged plants, favouring the
      preferred prey species.
AB  - Compared to terrestrial environments, grazing intensity on belowground plant
      parts may be particularly strong in aquatic environments, which may have great
      effects on plant-community structure. We observed that the submerged macrophyte,
      Potamogeton pectinatus, which mainly reproduces with tubers, often grows at
      intermediate water depth and that P. perfoliatus, which mainly reproduces with
      rhizomes and turions, grows in either shallow or deep water. One mechanism behind
      this distributional pattern may be that swans prefer to feed on P. pectinatus
      tubers at intermediate water depths. We hypothesised that when swans feed on
      tubers in the sediment, P. perfoliatus rhizomes and turions may be damaged by the
      uprooting, whereas the small round tubers of P. pectinatus that escaped herbivory
      may be more tolerant to this bioturbation. In spring 2000, we transplanted P.
      perfoliatus rhizomes into a P. pectinatus stand and followed growth in plots
      protected and unprotected, respectively, from bird foraging. Although swan
      foraging reduced tuber biomass in unprotected plots, leading to lower P.
      pectinatus density in spring 2001, this species grew well both in protected and
      unprotected plots later that summer. In contrast, swan grazing had a dramatic
      negative effect on P. perfoliatus that persisted throughout the summer of 2001,
      with close to no plants in the unprotected plots and high densities in the
      protected plots. Our results demonstrate that herbivorous waterbirds may play a
      crucial role in the distribution and prevalence of specific plant species.
      Furthermore, since their grazing benefitted their preferred food source, the
      interaction between swans and P. pectinatus may be classified as ecologically
      mutualistic.

PMID- 18335251
TI  - Antifungal skin bacteria, embryonic survival, and communal nesting in four-toed
      salamanders, Hemidactylium scutatum.
AB  - We examined a novel hypothesis for the maintenance of communal nesting in the
      salamander, Hemidactylium scutatum, namely that communal nests are more likely
      than solitary nests to be associated with cutaneous antifungal bacteria, which
      can inhibit fungal infections of embryos. A communal nest contains eggs of two or
      more females of the same species. The nesting behavior of H. scutatum females and
      survival of embryos were determined by frequent nest surveys at three ponds. For
      communal nests, embryonic survival tended to be higher and catastrophic nest
      failure was lower. Pure bacterial cultures of resident species were obtained from
      the salamanders' skins by swabbing and tested against a fungal pathogen of
      embryos (Mariannaea sp.) in laboratory assays. We found that 27% of females had
      skin bacteria inhibitory to Mariannaea sp. Communal nests were more likely to
      have at least one female with antifungal bacteria than were solitary nests. Using
      a culture-independent assay (denaturing gradient gel electrophoresis of 16S rRNA
      gene fragments), we found that bacterial species on females and embryos were more
      similar to each other than they were to bacterial species found in soil within
      the nest, suggesting that females transmitted skin bacteria to embryos. The
      presence of anti-Mariannaea skin bacteria identified from the laboratory assays
      did not prevent fungal presence in field nests. However, once a nest was visibly
      infected with fungi, presence of anti-Mariannaea bacteria was positively
      correlated with survival of embryos. Microbe transmission is usually thought to
      be a cost of group living, but communal nesting in H. scutatum may facilitate the
      transmission of antifungal bacteria to embryos.

PMID- 18335252
TI  - Therapeutic strategies to slow chronic kidney disease progression.
AB  - Childhood chronic kidney disease commonly progresses toward end-stage renal
      failure, largely independent of the underlying disorder, once a critical
      impairment of renal function has occurred. Hypertension and proteinuria are the
      most important independent risk factors for renal disease progression. Therefore,
      current therapeutic strategies to prevent progression aim at controlling blood
      pressure and reducing urinary protein excretion. Renin-angiotensin-system (RAS)
      antagonists preserve kidney function not only by lowering blood pressure but also
      by their antiproteinuric, antifibrotic, and anti-inflammatory properties.
      Intensified blood pressure control, probably aiming for a target blood pressure
      below the 75th percentile, may exert additional renoprotective effects. Other
      factors contributing in a multifactorial manner to renal disease progression
      include dyslipidemia, anemia, and disorders of mineral metabolism. Measures to
      preserve renal function should therefore also comprise the maintenance of
      hemoglobin, serum lipid, and calcium-phosphorus ion product levels in the normal
      range.

PMID- 18335253
TI  - A new approach to the diagnosis of children's urolithiasis based on the Bonn Risk
      Index.
AB  - Published data on the association between calcium oxalate (CaOx) crystallization
      and kidney stone disease in children are scarce. The aims of this study were to
      determine CaOx crystallization using the Bonn Risk Index (BRI) in children with
      urolithiasis in comparison to healthy controls, to evaluate the relationships
      between BRI and urinary parameters, such as pH, calciuria, oxaluria and
      citraturia, and to assess the association between BRI and the size of renal
      stones. We compared the BRI in 142 Caucasian children and adolescents (76 girls,
      66 boys) aged 3-18 years with kidney stones and 210 healthy age- and sex-matched
      controls without urolithiasis. Urinary ionized calcium ([Ca2+]) was measured
      using a selective electrode, while the onset of spontaneous crystallization was
      determined using a photometer and titration with 40 mmol/L ammonium oxalate (Ox2
      ). The calculation of the BRI value was based on the Ca2+:Ox2- ratio. High
      resolution renal ultrasonography was carried out to estimate the size of the
      renal stones. The BRI values were 15-fold higher in children with renal stones
      than in healthy children without stones. The same trend was shown by BRI/kg body
      weight (tenfold greater in children with renal stones than in healthy children
      without stones), BRI/per 1.73 m2 body surface (13-fold greater) and BRI/body mass
      index (23-fold greater). No association was observed between BRI and the diameter
      of stones. Children with kidney stones, both males and females, had an increased
      BRI compared with subjects without urolithiasis. High BRI suggests an association
      with lower urinary pH, hypercalciuria, hyperoxaluria or hypocitraturia, which are
      all risk factors of kidney stones. An increased BRI in children, although
      unrelated to renal stone size, reflects the risk of calcium oxalate
      crystallization and may indicate early metabolic disorders leading to
      urolithiasis.

PMID- 18335254
TI  - Intensified hemodialysis regimens: neglected treatment options for children and
      adolescents.
AB  - During recent years, the importance of intensified dialysis regimens has gathered
      increasing interest, especially after the Hemodialysis (HEMO) Study Group
      reported that a higher dose of thrice-weekly hemodialysis failed to improve
      clinical outcomes. Long nocturnal hemodialysis (three to six times per week) or
      short daily hemodialysis are the currently used forms of intensified dialysis.
      There is substantial evidence for cardiovascular and quality-of-life improvements
      as well as financial benefits with intensified hemodialysis. Preliminary
      experience with daily hemodialysis and hemodiafiltration in children has been
      reported. Given the continuing shortage of donor organs for kidney
      transplantation, the increasing incidence of end-stage renal disease (ESRD) and
      recognition of the deleterious effects of long-lasting ESRD, growth retardation,
      and poor social rehabilitation, more intensified dialysis regimens are a much
      needed therapeutical option in both adults and children.

PMID- 18335255
TI  - Non-invasive evaluation of voiding function in asymptomatic primary school
      children.
AB  - This study aimed to evaluate the voiding characteristics of primary school
      children by using questionnaires and non-invasive diagnostic tools. The voiding
      characteristics of 212 healthy children in two primary schools were evaluated
      with ultrasound for bladder wall thickness (BWT) in association with the
      Pediatric Lower Urinary Tract Symptom Score (PLUTSS), familial questionnaire,
      uroflowmetry (UF) and urinalysis. Most of the children (70%) had achieved urinary
      and fecal continence between the ages of 18 months and 36 months. Twenty-five per
      cent of healthy children void fewer than four times or more than seven times per
      day. Ninety percent of children had a PLUTSS within normal ranges (< 9). Fifteen
      percent of patients had a uroflowmetric pattern other than bell-shaped. The peak
      and average flow rates were higher in girls. Enuresis nocturna was detected in
      10% of children. None of the children had documented urinary tract infection. The
      average BWT from posterior wall at full bladder in healthy children was 1.1 mm.
      The anterior and posterior BWT measurements before and after micturition were
      found to be thicker in boys. Regarding the UF pattern, in post-voiding
      measurements in children with abnormal UF pattern, the bladder walls were
      thicker. Non-invasive tests in non-symptomatic children showed a range of
      variability, and these deviations should be kept in mind during the evaluation of
      voiding characteristics of a child. The symptom scoring system, with the high
      sensitivity and specificity rates it possesses, is one of the promising tools for
      this purpose.

PMID- 18335256
TI  - Feasibility study of the Montreal Cognitive Assessment (MoCA) in patients with
      brain metastases.
AB  - GOAL OF WORK: Detection of cognitive impairment in patients with brain metastases
      is important for both patient management and clinical trials. The most commonly
      used cognitive screen, the Mini Mental State Examination (MMSE), though
      convenient, is not sensitive in these patients. More sensitive tools are less
      convenient and, therefore, uncommonly used. Therefore, a practical and sensitive
      tool is needed. The Montreal Cognitive Assessment (MoCA) is a good candidate,
      shown to be sensitive in detecting mild cognitive impairment in the pre-dementia
      setting. This study is the first to explore the MoCA in cancer patients and is
      aimed at determining the feasibility of administering the MoCA in brain tumor
      patients. The secondary objective is to explore the relationship between MoCA and
      MMSE scores. PATIENTS AND METHODS: Forty patients with brain metastases being
      treated with whole brain radiotherapy were prospectively accrued from January to
      May 2007. All patients were administered both the MoCA and MMSE. MAIN RESULTS:
      The MoCA was completed in 10 min in 88% of patients. 92% of all the patients
      found the MoCA to be only mildly or not at all inconvenient. Eighty percent of
      the patients were deemed cognitively impaired by the MoCA compared with 30% by
      the MMSE (p < 0.0001). Of the 28 patients with a normal MMSE, 71% had cognitive
      impairment according to the MoCA. Overall, 50% of the patients had an abnormal
      MoCA, yet normal MMSE. CONCLUSION: The MoCA was well tolerated and provided
      additional information over the MMSE, justifying further validation studies of
      the MoCA in brain tumor patients.

PMID- 18335257
TI  - Attitudes toward active euthanasia among medical students at two German
      universities.
AB  - AIM: There has been an ongoing debate about a legalisation of active euthanasia
      (AE) in Germany. Palliative care education in German medical schools seeks to
      foster and cultivate a negative attitude toward AE, but little is known about its
      effectiveness in this respect. The aim of this study was to assess attitudes
      toward AE among students with and without palliative medicine tuition (PMT).
      METHODS: The link to an anonymised online questionnaire was sent out to 1,092
      third, fifth and sixth year medical students (YMS) in August-November 2006 at two
      German universities: university one (U1) with compulsory and additional optional
      PMT and university two (U2) without any PMT. Thirteen questions addressed active,
      passive or indirect euthanasia and physician-assisted suicide (statistic: mean +/
      SD (range), Wilcoxon, Whitney U Test, significance p < 0.05). RESULTS: Response
      rate was 17.5%; 59.2% of the questionnaires were returned from U1 and 40.8% from
      U2; 28.3% of the students were male. Whereas 50% of third YMS at U1 and 36.7% at
      U2 favoured a legalisation of AE, this was true for 22.4% sixth YMS at U1 and
      35.7% at U2. At U1, the number of students who would want to make use of AE for
      themselves decreased considerably (70%-44.9%) but less at U2; main reasons were
      'unbearable suffering' and 'circumstances that lack dignity'. Of all students,
      21.1% at U1 and 37.2% at U2 could imagine to perform AE in patients, even though
      72.6% at U1 and 78.2% at U2 think its legalisation would promote misuse.
      CONCLUSIONS: The high proportion of pro-AE attitudes gives reason to reconsider
      both 'standard' and palliative medicine tuition for medical students.

PMID- 18335258
TI  - Effects of educational intervention on nurses' knowledge, attitudes, and
      behavioral intentions toward supplying artificial nutrition and hydration to
      terminal cancer patients.
AB  - INTRODUCTION: This study aimed to investigate the effects of educational
      intervention on nurses' knowledge, attitudes, and behavioral intentions regarding
      supplying artificial nutrition and hydration (ANH) to terminal cancer patients.
      MATERIALS AND METHODS: A quasi-experimental design was adopted. A structured
      questionnaire evaluated the effects of educational intervention. From April to
      June 2005, 88 nurses were enrolled in the gastroenterology, general surgery, and
      intensive care unit of Taipei Veterans General Hospital in Taiwan. The nurses
      were randomly assigned into experimental and control groups in equal numbers (44
      nurses in each group). After the experimental and control groups completed the
      pretest, the experimental group participated in a 50-min lecture. Both groups
      received a post-test 2 weeks after the lecture. RESULTS: This study showed that
      prior to educational intervention, nurses have possessed experiences of ANH use
      in routine caring for terminal cancer patients. However, due to the lack of
      knowledge about supplying ANH to terminal cancer patients, the nurses trended
      toward the negative behavioral intention, although they realized the burdens of
      ANH in these patients. After educational intervention, mean scores of knowledge,
      attitudes and behavioral intentions of the experimental group increased
      significantly (z = -5.255, p < 0.001; t = -5.191, p < 0.001; z = -3.274, p <==
      0.001). Mean score changes of knowledge and attitude between these two groups
      reached significant differences (t = -7.306, p < 0.001; t = -4.165, p < 0.001),
      but no significant difference was observed in the mean score change of behavioral
      intention (z = -1.943, p > 0.05). CONCLUSION: The educational intervention
      remarkably improved nurses' knowledge and attitudes regarding supplying terminal
      cancer patients with ANH. As for the changes in the behavioral intentions, it
      requires long-term moral and ethical training and communication. The results of
      this research emphasized the importance of educational interventions, which
      should be considered seriously in future reference nursing education program.

PMID- 18335259
TI  - Comfort in the last 2 weeks of life: relationship to accessing palliative care
      services.
AB  - INTRODUCTION: Specialised palliative care services (SPCS) aim to address the
      needs of patients and caregivers confronting life-limiting illnesses but only
      half of the potential cohort are referred. Randomised controlled trials of SPCS
      provision can no longer be ethically justified so there is a need to develop new
      methods to evaluate the net impact of SPCS for the whole community, not just for
      those who access SPCS. The aim of this study was to assess whether perceived
      comfort in the last 2 weeks of life was associated with accessing SPCS. METHODS:
      This study utilised a whole-of-population random survey (n = 4,366) in South
      Australia. A total of 802 respondents had someone close to them die within the
      last 5 years due to a terminal illness, and they had the complete data. A
      subsequent question was asked whether SPCS had been accessed. Perceived comfort
      levels for those who had used SPCS were compared with those who did not by using
      stereotype logistic regression, weighted to a standardised population. RESULTS:
      Higher levels of comfort of the deceased having been assessed 'very comfortable'
      was associated with the use of SPCS (p = 0.04; odds ratio, 1.78; 95% confidence
      interval, 1.02-3.08). For people who accessed SPCS, 13.3% were reported as 'very
      comfortable' compared with 8.0% without SPCS. Almost one half of respondents
      (48.4%) reported that the deceased was considered 'uncomfortable' or 'very
      uncomfortable', irrespective of SPCS access. DISCUSSION: While this study
      provides further incremental evidence of benefit from access to SPCS, there is
      much that still needs to be done to improve care for the whole community at the
      end of life.

PMID- 18335260
TI  - A mixed-method evaluation of nurse-led community-based supportive cancer care.
AB  - GOALS OF WORK: The study purpose was to evaluate a nurse-led supportive care
      clinical case management program in the community using multi-methods to
      delineate care processes prior to outcome evaluation. MATERIALS AND METHODS:
      Multiple data sources including program service records, chart reviews and
      interviews with nurses and key interdisciplinary informants were used to identify
      population served (coverage and reach), processes of care (implementation), and
      providers' perceptions of the effectiveness of the nurse-led program (reaction).
      MAIN RESULTS: The program provided care to over 700 cancer patients in a 1-year
      period. Nurse-led support interventions were focused on direct care inclusive of
      teaching/coaching for symptom management, counseling and support, and
      mobilization of services through system navigation based on an initial
      comprehensive assessment of supportive care needs. CONCLUSIONS: Nurse-led models
      of supportive care have the potential to reduce unmet supportive care needs,
      improve continuity of care, and overall health-related quality of life that
      should be tested in future trials.

PMID- 18335261
TI  - Discrepancies of MRI findings between recumbent and upright positions in
      atlantoaxial lesion. Report of two cases.
AB  - Two cases of atlantoaxial (A-A) instability that showed different MRI findings
      between supine and upright positions are presented. The upright MRI represented
      the findings corresponding to their symptoms. In A-A lesions, conventional MR
      images taken in the supine position do not always explain the pathophysiological
      consequences. The MR images taken in the upright position disclose the actual
      spinal pathophysiology with gravitational effects.

PMID- 18335263
TI  - Obstructive rectal intramural hematoma caused by a foreign body.
AB  - Intramural hematoma of the alimentary tract is a rare condition, which usually
      results from blunt injury. It can spontaneously occur in patients with
      coagulopathy or on anticoagulants. Although it may be seen anywhere in the
      alimentary tract, duodenum is the most common site of the intestinal intramural
      hematomas. Intramural hematoma caused by a foreign body is rarely seen. Patients
      with intramural hematoma are usually encountered with obstructive symptoms after
      an isolated injury. Intramural hematomas are often self-limited at the site of
      occurrence and can be managed conservatively. They rarely cause progressive
      obstruction and need surgical drainage. In this article, we report a 51-year-old
      male patient with foreign body used for masturbation causing rectal intramural
      hematoma and perforation at the rectosigmoid junction. Because of the intestinal
      perforation, the patient was managed surgically. In the diagnosis of intramural
      hematoma of the alimentary tract, beside the clinical history and physical
      examination, the findings at imaging modalities such as conventional radiography,
      ultrasonography, and computed tomography are often useful. Patients with rectal
      intramural hematoma usually do not give diagnostic clues to the physicians in the
      clinical history. Therefore, radiologists must be familiar with the imaging
      findings. In this article, we aimed to present a patient with rectal intramural
      hematoma caused by foreign body and obliterating the rectal lumen.

PMID- 18335262
TI  - Differential expression of alpha-synuclein, parkin, and synphilin-1 isoforms in
      Lewy body disease.
AB  - Alpha-synuclein, parkin, and synphilin-1 are proteins mainly involved in the
      pathogenesis of Lewy body (LB) diseases. mRNAs of all three undergo alternative
      splicing, so that the existence of various isoforms has been described. Since
      increasing evidence supports the importance of differential isoform-expression
      changes in disease development, we have established isoform-expression profiles
      in frontal cortices of LB disease brains in comparison with those of Alzheimer
      disease (AD) and control frontal cortices. The differential expression of four
      alpha-synuclein, seven parkin, and four synphilin-1 isoforms was ascertained by
      the use of isoform-specific primers and relative expression analysis with
      SybrGreen and beta-actin as an internal standard. The establishment of isoform
      expression profiles revealed that these are disease specific. Moreover, isoform
      expression deregulation of mainly one gene in each disease could be observed. All
      four alpha-synuclein isoforms were affected in the case of the pure form of
      dementia with LB, most parkin transcript variants in common LB disease, and all
      synphilin-1 isoforms in Parkinson disease. Only minor involvement was detected in
      AD. Finally, the existence of a proprietary isoform-expression profile in common
      LB disease indicates that this disease develops as a result of its own molecular
      mechanisms, and so, at the molecular level, it does not exactly share changes
      found in pure dementia with LB and AD. In conclusion, isoform-expression profiles
      in LB diseases represent additional evidence for the direct involvement of
      isoform-expression deregulation in the development of neurodegenerative
      disorders.

PMID- 18335264
TI  - Low-grade urinary albumin excretion in normotensive/non-diabetic obstructive
      sleep apnea patients.
AB  - Previous studies have indicated that high levels of urinary albumin excretion
      (UAE) are associated with an increased incidence of cardiovascular morbidity and
      mortality. This study examined the association between UAE and obstructive sleep
      apnea syndrome (OSAS). The study included 35 newly diagnosed OSAS patients and 11
      nonapneic controls. Subjects with diabetes mellitus, hypertension, a history of
      renal failure, cardiac failure, coronary heart disease, collagen tissue disease,
      high serum creatinine, and urinary infection, and who use angiotensin-converting
      enzyme inhibitors and were women were excluded from the study. A single void
      morning urine sample at the baseline examination was used to measure UAE. There
      were no significant differences in the age, body mass index (BMI), and smoking
      habits of the OSAS patients and controls. UAE of the OSAS group was significantly
      higher than that of the control group (23.3 +/- 6.1 microg/min vs. 6.5 +/- 2.1
      microg/min, respectively; P = 0.002). UAE was positively correlated to length of
      time spent at an oxygen saturation of <90% (r = 0.503, P = 0.002) and BMI (r =
      0.361, P = 0.033). Regression analyses (r (2) = 0.504, P < 0.0001) showed that
      the length of time spent at an oxygen saturation of <90% (P < 0.0001) was risk
      factor for UAE, independent of age and BMI. Our study supports the notion that
      low-grade UAE is associated with non-hypertensive/non-diabetic OSAS, independent
      of age and BMI. Low-grade UAE may be a marker for subclinical vascular damage
      that predisposes OSAS patients to future cardiovascular disease.

PMID- 18335265
TI  - From aquatic to terrestrial food webs: decrease of the docosahexaenoic
      acid/linoleic acid ratio.
AB  - Fatty acid composition of the adipose tissue of six carnivorous mammalian species
      (European otter Lutra lutra, American mink Mustela vison, European Mink Mustela
      lutreola, European polecat Mustela putorius, stone marten Martes foina and
      European wild cat Felis silvestris) was studied. These species forage to
      differing degrees in aquatic and terrestrial food webs. Fatty acid analysis
      revealed significant differences in polyunsaturated fatty acid composition
      between species. More specifically, our results underline a gradual significant
      decrease in the docosahexaenoic acid (DHA)/linoleic acid (LNA) ratio of carnivore
      species as their dependence on aquatic food webs decreases. In conclusion, the
      use of the DHA/LNA ratio in long-term studies is proposed as a potential proxy of
      changes in foraging behaviour of semi-aquatic mammals.

PMID- 18335266
TI  - Hepatic and adipose tissue depot-specific changes in lipid metabolism in Late
      onset Obese (LOB) rats.
AB  - Transgenic Late-onset OBesity (LOB) rats slowly develop a male-specific,
      autosomal dominant, obesity phenotype with a specific increase in peri-renal
      white adipose tissue (WAT) depot and preserved insulin sensitivity (Bains et al.
      in Endocrinology 145:2666-2679, 2004). To better understand the remarkable
      phenotype of these rats, the lipid metabolism was investigated in male LOB and
      non-transgenic (NT) littermates. Total plasma cholesterol (C) levels were normal
      but total plasma triacylglycerol (TAG) (2.8-fold) and hepatic TAG content (25%)
      was elevated in LOB males. Plasma VLDL-C and VLDL-TAG levels were higher while
      plasma apoB levels were 60% lower in LOB males. Increased hepatic TAG secretion
      explained the increased VLDL levels in LOB males. The hepatic gene expression of
      FAS, SCD-1, mitochondrial (mt)GPAT, and DGAT2 was up-regulated in both old obese
      and young non-obese LOB rats. Lipoprotein lipase (LPL) activity in heart and
      epididymal white adipose tissue (WAT) was unchanged, while LPL activity was
      increased in peri-renal WAT (30%) and decreased in soleus muscle (40%). Moreover,
      FAS, SCD-1 and DGAT2 gene expression was increased in peri-renal, but not in
      epididymal WAT. Basal lipolysis was reduced or unchanged and beta-adrenergic
      stimulated lipolysis was reduced in WAT from both old obese and young non-obese
      LOB rats. To summarize, the obese phenotype of LOB male rats is associated with
      increased hepatic TAG production and secretion, a shift in LPL activity from
      skeletal muscle to WAT, reduced lipolytic response in WAT depots and a specific
      increase in expression of genes responsible for fatty acid and TAG synthesis in
      the peri-renal depot.

PMID- 18335267
TI  - Inhibition of serum cholesterol oxidation by dietary vitamin C and selenium
      intake in high fat fed rats.
AB  - Cholesterol oxidation products (COPs) have been considered as specific in vivo
      markers of oxidative stress. In this study, an increased oxidative status was
      induced in Wistar rats by feeding them a high-fat diet (cafeteria diet). Another
      group of animals received the same diet supplemented with a combination of two
      different antioxidants, ascorbic acid (100 mg/kg rat/day) and sodium selenite
      (200 microg/kg rat/day) and a third group fed on a control diet. Total and
      individual COPs analysis of the different diets showed no differences among them.
      At the end of the experimental trial, rats were sacrificed and serum cholesterol,
      triglycerides and COPs were measured. None of the diets induced changes in rats
      body weight, total cholesterol and triglycerides levels. Serum total COPs in rats
      fed on the high-fat diet were 1.01 microg/ml, two times the amount of the control
      rats (0.47 microg/ml). When dietary antioxidant supplementation was given, serum
      total COPs concentration (0.44 microg/ml) showed the same levels than those of
      the rats on control diet. 7beta-hydroxycholesterol, formed non-enzymatically via
      cholesterol peroxidation in the presence of reactive oxygen species, showed
      slightly lower values in the antioxidant-supplemented animals compared to the
      control ones. This study confirms the importance of dietary antioxidants as
      protective factors against the formation of oxysterols.

PMID- 18335268
TI  - Structural importance of the acyl group in substrate specificity of purified
      bovine lysophospholipase D.
AB  - The structural importance of the acyl group in lysophosphatidylcholine (LPC) as
      substrate of purified bovine lysophospholipase D (lysoPLD) was investigated.
      Among LPCs with saturated acyl chains, the K(m) value decreased according to the
      length of the acyl chain (C12-C16) up to the palmitoyl group, while the V(m)
      value showed no remarkable change. But, the extension of the acyl size to C18, as
      observed with 1-stearoyl LPC (K(m), 8.5 mM), rather resulted in a remarkable
      increase in the K(m) value. Meanwhile, the introduction of one double bond in the
      C18 saturated acyl chain led to a remarkable reduction in the K(m) value, as
      observed with 1-oleoyl LPC (K(m), 0.48 mM). Furthermore, 1-linoleoyl LPC (K(m),
      56 microM) with two double bonds exhibited a smaller K(m) value than 1-oleoyl
      LPC, suggesting that the unsaturation degree might be important in augmenting the
      binding affinity of LPCs. A similar phenomenon was also observed with 1
      arachidonoly LPC (K(m), 79 microM) or 1-docosahexaenoyl LPC (K(m), 36 microM).
      Overall, the order of catalytic efficiency (V(m)/K(m) value) of those LPCs seemed
      to be affected by the K(m) value rather than the V(m) value, which differed by at
      most threefold among LPC derivatives. Next, the introduction of a hydroperoxide
      group into 1-linoleoyl-LPC or 1-arachidonoyl LPC led to a further reduction in
      K(m) values (1-hydroperoxylinoleoyl LPC, 26 microM; 1-hydroperoxyarachidonoyl
      LPC, 33 microM), accompanied by a further increase in the V(m)/K(m) values.
      Additionally, phosphatidylcholines (PCs) with an oxidized acyl chain at sn-2
      position were found to be efficient as 1-palmitoyl LPC as substrates of lysoPLD.
      Taken together, the catalytic efficiency of LPCs or oxidized PCs as substrates of
      lysoPLD seems to be determined by the property of the acyl chain, length of the
      acyl chain, unsaturation degree and oxidation status.

PMID- 18335269
TI  - Molecular mechanism of age-specific hepatic lipid accumulation in PPARalpha (+/
      ):LDLR (+/-) mice, an obese mouse model.
AB  - This study aimed to clarify the molecular mechanisms of age-specific hepatic
      lipid accumulation accompanying hyperinsulinemia in a peroxisome proliferator
      activated receptor alpha (PPARalpha) (+/-):low-density lipoprotein receptor
      (LDLR) (+/-) mouse line. The hepatic fat content, protein amounts, and mRNA
      levels of genes involved in hepatic lipid metabolism were analyzed in 25-, 50-,
      75- and 100-week-old mice. Severe fatty liver was confirmed only in 50- and 75
      week-old mice. The hepatic expression of proteins that function in lipid
      transport and catabolism did not differ among the groups. In contrast, the mRNA
      levels and protein amounts of lipogenic enzymes, including acetyl-coenzyme A
      carboxylase-1, fatty acid synthase, and glycerol-3-phosphate acyltransferase,
      enhanced in the mice with fatty liver. Elevated mRNA and protein levels of
      lipoprotein lipase and fatty acid translocase, which are involved in hepatic
      lipid uptake, were also detected in mice with fatty liver. Moreover, both protein
      and mRNA levels of sterol regulatory element-binding protein-1 (SREBP-1), a
      transcription factor regulating lipid synthesis, had age-specific patterns
      similar to those of the proteins described above. Therefore, the age-specific
      fatty liver found in the PPARalpha (+/-):LDLR (+/-) mouse line is probably caused
      by age-specific expression of SREBP-1 and its downstream lipogenic genes,
      coordinated by the increased uptake of lipids. All of these factors might be
      affected by age-specific changes in serum insulin concentration.

PMID- 18335270
TI  - Conjugated linoleic acids and CLA-containing phospholipids inhibit NO formation
      in aortic endothelial cells.
AB  - This study examined the effects of five CLA isomers and the non-conjugated LA on
      nitric oxide (NO) production, an important modulator of vasodilation,
      inflammation, and cytotoxicity. Bovine aortic endothelial cells (BAECs) were
      pretreated with pure CLAs (c9, c11-, c9, t11-, t9, t11-, t10, c12-, c11, c13-CLA)
      and the non-conjugated c9, c12-analog, then stimulated by the ionophore A23187
      followed by fluorescence monitoring of NO production. CLAs (5 microM) decreased
      NO formation in the range of 20-40% relative to non-fatty acid-treated controls
      with the t9, t11- and t10, c12-CLAs being the most effective. The inhibitory
      effect of either of these CLAs was not time dependent over a 120 min time
      interval. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) play crucial
      roles in membrane structure and cell signaling. Since CLAs are usually esterified
      in these phospholipids (PLs), the effects of three CLA-containing PLs and 2
      linoleoyl-PC on NO production by A23187-stimulated BAECs were also examined. c9,
      t11-CLA-PC and 2-linoleoyl-PC dose-dependently inhibited NO production over a 60
      1,000 microM concentration range whereas c9, c11-CLA-PC and c9, t11-CLA-PE were
      ineffective. Both c9, t11-CLA-PC and linoleoyl-PC exhibited a time-dependent
      decrease in NO production from 5 to 120 min. The results of the present study
      suggest that the influence of several C18 polyunsaturated fatty acids
      incorporated into cellular phospholipids on the A23187-induced formation of NO by
      BAECs is strongly dependent on the positional and geometric nature of the double
      bonds.

PMID- 18335273
TI  - Surgical experience with pancreatic and peripancreatic neuroendocrine tumors:
      Review of 125 patients.
AB  - Neuroendocrine tumors of the pancreas and peripancreatic area are rare entities
      with a wide spectrum of clinical presentation. This study retrospectively reviews
      the patients who underwent surgery for these tumors at The Johns Hopkins Hospital
      from 1949 to 1996, inclusive There were 125 patients (65 males and 60 females)
      whose mean age was 51 +/- 1 years Fifty-eight patients (48%) had nonfunctional
      tumors, whereas 64 (52%) had functional tumors 35 (55%) insulinomas, 23 (36%)
      gastrmomas, three (5%) VIP-omas, two (3 %) glucagonomas, and one (1%) ACTHorna
      All patients with functional tumors presented with appropriate signs and symptoms
      of hormonal excess, 86% of patients with nonfunctional tumors presented with
      weight loss, abdominal pain, or jaundice Preoperauve computed tomography (CT)
      correctly localized the tumor in 66 (76%) of 87 patients, angiography in 45 (58%)
      of 78 patients, and CT plus angiography in 54 (79%) of 68 patients Tumors were
      benign in 60 patients (48%), malignant m 65 patients (52%), and were located in
      the head, neck, or uncinate process of the pancreas in 54, body in 14, tail in
      18, and duodenum in eight The most common operative procedures performed were 50
      pancreaacoduodenectomies (40%), 39 distal pancreatectomies (31%), and 21 tumor
      enucleations (17%) Nine synchronous hepatic resections were performed for
      metastases Of the evaluable patients, 46 (43%) had postoperative complications,
      the most common of which were pancreatic fistula (16%), wound infection (15%),
      and delayed gastric emptying (8%) There were three in-hospital deaths (2 8%) With
      a mean follow-up of 55 +/-6 months, there have been 30 additional deaths, 23 of
      which were related to disease progression The overall 2-, 5-, and 10-year
      actuarial survival rates were 82%, 65%, and 47%, respectively The 5-year survival
      for patients with functional tumors was 77% compared to 52% for those with
      nonfunctional tumors (P = 0 025), the 5-year survival for patients with benign
      tumors was 91% compared to 49% for those with malignant tumors (P = 0 0004) By
      univanate analysis the most powerful predictor of poor outcome for patients with
      malignant tumors (n = 60) was positive surgiad margins (P = 0 006) This single
      institution experience documents low mortality and moderate morbidity for
      patients treated operatively for pancreatic and penpancreaac neuroendocrine
      tumors The most favorable outcomes are observed in patients with benign
      functional tumors and in those with completely resected malignant tumors.

PMID- 18335274
TI  - Practice guidelines for patients with gastrointestinal surgical diseases.
AB  - CONCLUSIONS: The rauonale for practice gmdehnes has been elucidated It is hoped
      that these guldehnes will result in changes in chnlcal care Perhaps the origin of
      these guldehnes may be a cnucal factor m whether they become widely accepted. Our
      purpose in developing guldehnes for gastrolntesunal surgical disorders is to
      promulgate reformation that is needed to evaluate patients with diseases that
      require surgery and to provide mformatlon concerning expected outcomes following
      specific operattve procedures As pracuce patterns and technology evolve, these
      guldehnes will need to be changed accordingly.

PMID- 18335275
TI  - Applying modern error theory to the problem of missed injuries in trauma.
AB  - BACKGROUND: Modern theory of human error has helped reduce the incidence of
      adverse events in commercial aviation. It remains unclear whether these lessons
      are applicable to adverse events in trauma surgery. Missed injuries in a large
      metropolitan surgical service were prospectively audited and analyzed using a
      modern error taxonomy to define its applicability to trauma. METHODS: A
      prospective database of all patients who experienced a missed injury during a 6
      month period in a busy surgical service was maintained from July 2006. A missed
      injury was defined as one that escaped detection from primary assessment to
      operative exploration. Each missed injury was recorded and categorized. The
      clinical significance of the error and the level of physician responsible was
      documented. Errors were divided into planning or execution errors, acts of
      omission or commission, or violations, slips, and lapses. RESULTS: A total of
      1,024 trauma patients were treated by the surgical services over the 6-month
      period from July to December 2006 in Pietermaritzburg. Thirty-four patients
      (2.5%) with missed injuries were identified during this period. There were 29 men
      and 5 women with an average age of 29 years (range: 21-67 years). In 14 patients,
      errors were related to inadequate clinical assessment. In 11 patients errors
      involved the misinterpretation of, or failure to respond to radiological imaging.
      There were 9 cases in which an injury was missed during surgical exploration.
      Overall mortality was 27% (9 patients). In 5 cases death was directly
      attributable to the missed injury. The level of the physicians making the error
      was consultant surgeon (4 cases), resident in training (15 cases), career medical
      officer (2 cases), referring doctor (6 cases). CONCLUSIONS: Missed injuries are
      uncommon and are made by all grades of staff. They are associated with increased
      morbidity and mortality. Understanding the pattern of these errors may help
      develop error-reduction strategies. Current taxonomies help in understanding the
      error process, but efforts must be made to develop innovative mechanisms that
      reduce the potential for error.

PMID- 18335276
TI  - High success rate of parathyroid reoperation may be achieved with improved
      localization diagnosis.
AB  - INTRODUCTION: Because of the difficulty of reoperative parathyroid surgery,
      preoperative imaging studies have been increasingly adopted. We report the use of
      consistently applied localization diagnosis to yield high success rates in
      parathyroid reoperations. METHODS: Parathyroid reoperation was performed after
      previous parathyroid surgery in 144 patients with nonmalignant
      hyperparathyroidism (HPT) between 1962 and 2007. From the year 2000, 46 patients
      who underwent parathyroid reoperation and 14 patients who were subjected to
      thyroid surgery before primary parathyroid operation were investigated with
      sestamibi scintigraphy (MIBI), 11C-methionine PET/CT (met-PET), surgeon-performed
      ultrasound (US), US-guided fine-needle aspiration biopsy (US-FNA), and selective
      venous sampling (SVS) with rapid PTH (Q-PTH) analyses. When imaging was
      considered adequate, additional studies were generally not obtained. RESULTS:
      Reversal of hypercalcemia was achieved by reoperation in 134 of 144 (93%) of all
      patients with previous parathyroid surgery. In patients operated from year 2000,
      MIBI had 90% sensitivity and 88% predictive value, met-PET 79% sensitivity and
      87% predictive value, and US 72% sensitivity and 93% predictive value. SVS with Q
      PTH analyses provided accurate localization or regionalization in 11 of 11
      recently selected patients. Q-PTH analyses in fine-needle aspirations verified
      parathyroid origin of excised specimens, and intraoperative Q-PTH helped decide
      when operations could be terminated. In patients subjected to the algorithm of
      imaging procedures, reversal of hypercalcemia and apparent cure was obtained
      after the reoperation in 45 of 46 patients with previous parathyroid surgery,
      implying a success rate of 98%, and in all patients with previous thyroid
      surgery. CONCLUSIONS: Reoperative parathyroid surgery is challenging. Results can
      be improved by consistently applied sensitive methods of preoperative imaging,
      and reoperative procedures may then achieve nearly the same success rates as
      primary operations.

PMID- 18335277
TI  - Role for limited neck exploration in young adults with apparently sporadic
      primary hyperparathyroidism.
AB  - BACKGROUND: The risk of multiglandular disease (MGD) dictates the extent of
      exploration in patients with primary hyperparathyroidism (PHPT). Historically,
      young patients with PHPT were more likely to have MGD, but the existing
      literature is sparse and conflicting. We hypothesized that young adults (ages 16
      40 years) without familial PHPT have a disease process similar to that in older
      patients. METHODS: A 22-year retrospective chart review was performed on patients
      who underwent neck exploration for PHPT at our tertiary care center. Altogether,
      708 charts were reviewed for demographics, family history, laboratory values,
      operative findings, pathology, and outcomes. RESULTS: As a group, young adults
      comprised 14.0% of the total population and were more likely to have preexisting
      familial disorders of PHPT (p < 0.01), therapeutic failure (p < 0.01), failure to
      identify an abnormal parathyroid at operation (p < 0.01), and higher reoperative
      rates (p = 0.02); they were less likely to have single-gland disease (p = 0.04).
      Young adults without a family history of the disease demonstrated no disease
      differences except for a higher rate of symptoms (p < 0.01). Additional analysis
      found that patients with a family history of hypercalcemia, a sole family member
      with PHPT, or nephrolithiasis ("possible" family history) were more likely to
      have MGD (relative risk 2.0). CONCLUSIONS: In this largest single-institution
      study of young adults with sporadic PHPT, we conclude that sporadic PHPT in young
      adults represents a disease entity similar to that in older patients, with no
      increased risk for MGD, and hence they can be managed with a similar surgical
      approach. Further studies are needed to assess the role of a "possible" family
      history as a risk factor for MGD.

PMID- 18335278
TI  - Assessment of the role of chemotaxis and biofilm formation as requirements for
      colonization of roots and seeds of soybean plants by Bacillus amyloliquefaciens
      BNM339.
AB  - This article correlates colonization with parameters, such as chemotaxis, biofilm
      formation, and bacterial growth, that are believed to be connected. We show here,
      by using two varieties of soybean plants that seeds axenically produced exudates,
      induced a chemotactic response in Bacillus amyloliquefaciens, whereas root
      exudates did not, even when the exudates, also collected under axenic conditions,
      were concentrated up to 200-fold. Root exudates did not support bacterial cell
      division, whereas seed exudates contain compounds that support active cell
      division and high cell biomass at stationary phase. Seed exudates of the two
      soybean varieties also induced biofilm formation. B. amyloliquefaciens colonized
      both seeds and roots, and plant variety significantly affected bacterial root
      colonization, whereas it did not affect seed colonization. Colonization of roots
      in B. amyloliquefaciens occurred despite the lack of chemotaxis and growth
      stimulation by root exudates. The data presented in this article suggest that
      soybean seed colonization, but not root colonization, by B. amyloliquefaciens is
      influenced by chemotaxis, growth, and biofilm formation and that this may be
      caused by qualitative changes of the composition of root exudates.

PMID- 18335279
TI  - Ageing and hepatic steatosis exacerbate ischemia/reperfusion-accelerated
      outgrowth of colorectal micrometastases.
AB  - BACKGROUND: Ischemia/reperfusion (I/R) injury is frequently encountered during
      hepatic surgery. We recently showed that I/R accelerates the outgrowth of pre
      established colorectal micrometastases. The aim of this study was to assess the
      influence of ischemia time, gender, age, and liver steatosis on the accelerated
      outgrowth of colorectal metastases following I/R. METHODS: Five days after tumor
      cell inoculation, mice were subjected to 20, 30 or 45 min of left lobar I/R. To
      assess the influence of age, gender, and liver steatosis on I/R-accelerated tumor
      growth, we compared old with young mice, male with female mice, and mice with
      healthy livers with mice with steatotic livers. Endpoints were extent of tissue
      necrosis and tumor growth. RESULTS: With increasing ischemia times, tissue
      necrosis and I/R-accelerated tumor growth increased, with a significant
      stimulatory effect at 30 and 45 min of ischemia. I/R-stimulated outgrowth of
      micrometastases was further increased by 33% in aged mice and by 42% in steatotic
      livers and was associated with increased tissue necrosis. In female mice tissue
      necrosis had decreased by 47% and tumor growth was reduced in both control and
      clamped liver lobes. The stimulatory effect of I/R on metastasis outgrowth was
      similar in male and female mice. CONCLUSIONS: I/R-accelerated outgrowth of
      colorectal micrometastases largely depends on the duration of the ischemic
      period, with a safe upper limit of 20 min in mice. The stimulatory effects of I/R
      on tumor growth are exacerbated in aged mice and in steatotic livers.

PMID- 18335280
TI  - Random plasma glucose in serendipitous screening for glucose intolerance:
      screening for impaired glucose tolerance study 2.
AB  - BACKGROUND: With positive results from diabetes prevention studies, there is
      interest in convenient ways to incorporate screening for glucose intolerance into
      routine care and to limit the need for fasting diagnostic tests. OBJECTIVE: The
      aim of this study is to determine whether random plasma glucose (RPG) could be
      used to screen for glucose intolerance. DESIGN: This is a cross-sectional study.
      PARTICIPANTS: The participants of this study include a voluntary sample of 990
      adults not known to have diabetes. MEASUREMENTS: RPG was measured, and each
      subject had a 75-g oral glucose tolerance test several weeks later. Glucose
      intolerance targets included diabetes, impaired glucose tolerance (IGT), and
      impaired fasting glucose(110) (IFG(110); fasting glucose, 110-125 mg/dl, and 2 h
      glucose < 140 mg/dl). Screening performance was measured by area under receiver
      operating characteristic curves (AROC). RESULTS: Mean age was 48 years, and body
      mass index (BMI) was 30.4 kg/m(2); 66% were women, and 52% were black; 5.1% had
      previously unrecognized diabetes, and 24.0% had any "high-risk" glucose
      intolerance (diabetes or IGT or IFG(110)). The AROC was 0.80 (95% CI 0.74-0.86)
      for RPG to identify diabetes and 0.72 (0.68-0.75) to identify any glucose
      intolerance, both highly significant (p < 0.001). Screening performance was
      generally consistent at different times of the day, regardless of meal status,
      and across a range of risk factors such as age, BMI, high density lipoprotein
      cholesterol, triglycerides, and blood pressure. CONCLUSIONS: RPG values should be
      considered by health care providers to be an opportunistic initial screening test
      and used to prompt further evaluation of patients at risk of glucose intolerance.
      Such "serendipitous screening" could help to identify unrecognized diabetes and
      prediabetes.

PMID- 18335281
TI  - Validation of screening questions for limited health literacy in a large VA
      outpatient population.
AB  - OBJECTIVES: Previous studies have shown that a single question may identify
      individuals with inadequate health literacy. We evaluated and compared the
      performance of 3 health literacy screening questions for detecting patients with
      inadequate or marginal health literacy in a large VA population. METHODS: We
      conducted in-person interviews among a random sample of patients from 4 VA
      medical centers that included 3 health literacy screening questions and 2
      validated health literacy measures. Patients were classified as having
      inadequate, marginal, or adequate health literacy based on the Short Test of
      Functional Health Literacy in Adults (S-TOFHLA) and the Rapid Estimate of Adult
      Literacy in Medicine (REALM). We evaluated the ability of each of 3 questions to
      detect: 1) inadequate and the combination of "inadequate or marginal" health
      literacy based on the S-TOFHLA and 2) inadequate and the combination of
      "inadequate or marginal" health literacy based on the REALM. MEASUREMENTS AND
      MAIN RESULTS: Of 4,384 patients, 1,796 (41%) completed interviews. The
      prevalences of inadequate health literacy were 6.8% and 4.2%, based on the S
      TOHFLA and REALM, respectively. Comparable prevalences for marginal health
      literacy were 7.4% and 17%, respectively. For detecting inadequate health
      literacy, "How confident are you filling out medical forms by yourself?" had the
      largest area under the Receiver Operating Characteristic Curve (AUROC) of 0.74
      (95% CI: 0.69-0.79) and 0.84 (95% CI: 0.79-0.89) based on the S-TOFHLA and REALM,
      respectively. AUROCs were lower for detecting "inadequate or marginal" health
      literacy than for detecting inadequate health literacy for each of the 3
      questions. CONCLUSION: A single question may be useful for detecting patients
      with inadequate health literacy in a VA population.

PMID- 18335282
TI  - Preoperative psychological testing--another form of prejudice.
AB  - Preoperative psychological screening of bariatric surgery candidates has become
      routine, and a significant proportion of patients have their surgery deferred as
      a consequence. If psychological testing is being used as a form of preoperative
      triage, both patients and surgeons are entitled to know whether there is
      sufficient evidence to justify its use in this way. We define the argument for
      psychological screening as consisting of four premises (p1-p4) and a conclusion
      (C) as follows: (p1) A significant minority of obese patients will not be
      successful in losing weight following bariatric surgery-the "failure" group; (p2)
      A significant minority of patients will exhibit abnormal psychological profiles
      during preoperative testing; (p3) The majority of individuals referred to in (p2)
      will be found in group (p1) i.e., abnormal psychological profiles identified
      preoperatively predict less favorable weight loss outcomes postoperatively; (p4)
      Identifying patients with adverse psychological profiles preoperatively would
      allow either exclusion of those at high risk of failure or provide a more secure
      rationale for targeted pre- and postoperative support; (C) Psychological
      screening should be part of the routine preoperative assessment for patients
      undergoing obesity surgery. We reviewed the literature to find evidence to
      support the premises and show that (p1) can be justified but that (p2) is
      problematic and can only be accepted in a heavily qualified version. We find no
      evidence for (p3) and since (p4) and (C) are predicated on (p3), the argument
      clearly fails. There is no evidence to suggest that preoperative psychological
      screening can predict postoperative outcomes and no justification for using such
      testing as a means of discriminating between candidates presenting themselves for
      bariatric surgery.

PMID- 18335296
TI  - Developmental dysplasia of the hip : editorial comment.

PMID- 18335295
TI  - Markers of bone and calcium metabolism following gastric bypass and laparoscopic
      adjustable gastric banding.
AB  - BACKGROUND: Several studies have suggested that morbid obesity is associated with
      vitamin D deficiency and elevated parathyroid hormone (PTH). Studies have also
      suggested that there is an increase in vitamin D deficiency, bone resorption, and
      elevated PTH after gastric bypass surgery. Few studies have evaluated markers of
      bone and calcium metabolism after laparoscopic adjustable gastric banding or
      compared these results to those after gastric bypass. METHODS: Data on all
      patients undergoing primary gastric bypass (GBP; n = 979) and laparoscopic
      adjustable gastric banding (LAGB; n = 269) procedures at a tertiary-referral
      center from June 1996 through March 2005 were reviewed from a prospective
      database. Only patients with 25OH vitamin D levels available were included in
      this study (n = 534; GBP = 403, LAGB = 131). All patients were advised to take at
      least 1,200 mg calcium and 800-1,200 IU of vitamin D daily before and subsequent
      to their operation. Markers for bone metabolism [25OH Vitamin D, corrected serum
      calcium, alkaline phosphatase (AP), and PTH] were evaluated preoperatively and 3,
      6, 12, and 24 months postoperatively. An analysis of variance and chi-square were
      performed to determine differences between the operative groups. Linear
      regression analysis was performed to evaluate the relationship between
      preoperative body mass index (BMI) and 25OH vitamin D and PTH levels and between
      percent excess weight loss and 25OH vitamin D and PTH after surgery. RESULTS:
      Sixty-four percent of all patients presented with vitamin D deficiency (<20
      ng/ml) and 14% presented with elevated PTH preoperatively. Mean 25OH vitamin D
      levels and AP levels increased significantly after GBP surgery (vitamin D, 17 to
      25 ng/ml 12 months post-op; AP, 80 to 90 IU/L 24 months post-op). Corrected
      calcium levels remained within normal limits and showed no change over time after
      both procedures. AP levels significantly increased from 76 IU/l preoperatively to
      82 IU/l 6 months after LAGB surgery and then decreased to 59 IU/l 24 months after
      LAGB surgery. Linear regression analysis of preoperative vitamin D, PTH, and BMI
      values showed a significant positive relationship between initial BMI and PTH (r
      = 0.29) and a significant negative relationship between vitamin D and initial BMI
      (r = -0.19). A significant positive linear relationship between vitamin D and
      percent excess weight loss was evident 12 and 24 months after GBP surgery (r =
      0.39 and 0.57, respectively). A negative relationship was evident between PTH and
      vitamin D 6 months after GBP surgery (r = -0.35) and 12 months after LAGB surgery
      (r = -0.61). CONCLUSIONS: These findings suggest that morbid obesity is
      associated with vitamin D deficiency, and elevated PTH and with adequate
      supplementation, GBP, and particularly LAGB, patients can improve their bone
      metabolism abnormalities related to obesity. Furthermore, adequate
      supplementation for GBP patients may attenuate the increased risk for bone loss
      associated with malabsorption from the bypass.

PMID- 18335297
TI  - The limbus and the neolimbus in developmental dysplasia of the hip.
AB  - The limbus and the neolimbus are both pathological lesions that form in response
      to a developmentally dislocated hip. An understanding of these structures is
      integral to treatment of developmental dysplasia of the hip (DDH). Yet, we
      believe the current peer-reviewed orthopaedic literature and orthopaedic
      textbooks commonly fail to correctly use or define these terms. The neolimbus is
      best defined as a hypertrophied ridge of fibrocartilage in the superolateral
      region of the acetabulum caused by pressure from the dislocated hip on this
      region. The limbus is the labrum that is hypertrophied with fibrous and
      fibrocartilaginous overgrowth, and is a potential block to concentric reduction
      of a dysplastic hip. We review the early and current literature in an attempt to
      clarify the use of the terms limbus and neolimbus and provide an overview of the
      importance and treatment of these abnormal structures associated with DDH. LEVEL
      OF EVIDENCE: Level V, therapeutic study. See the Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 18335298
TI  - Weightbearing anteroposterior pelvic radiographs are recommended in DDH
      assessment.
AB  - Neutral pelvic positioning during recording of anteroposterior pelvic radiographs
      has been recommended for precise interpretation of acetabular deformities.
      Because the effect of pelvic positioning is controversial in the literature, we
      asked whether the weightbearing position would alter radiographic
      interpretations. We obtained sets of supine and weightbearing anteroposterior
      pelvic radiographs of 31 patients with developmental dysplasia of the hip and
      measured pelvic tilt, acetabular version, center edge angle, acetabular index,
      joint space width and femoral head translation. For both genders the pelvis
      extended when patients were repositioned from supine to weightbearing but
      extension was more pronounced in women compared with men. The number of patients
      with apparent acetabular retroversion was reduced from 11 supine to four when
      weightbearing. The center edge angle, acetabular index, joint space width and
      femoral head translation were similar in both views. We recommend weightbearing
      anteroposterior pelvic radiographs be obtained to assess DDH given the
      differences in pelvic flexion-extension and interpretations of acetabular
      version. LEVEL OF EVIDENCE: Level III, diagnostic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18335299
TI  - How are outcomes affected by combining the Pemberton and Salter osteotomies?
AB  - The Pembersal operation combines features of the Pemberton and Salter
      osteotomies. Results have usually been reported in patients with dysplasia but
      without frank dislocation. We asked if the following factors influence the
      outcome of the Pembersal operation in patients with dislocated hips: triradiate
      cartilage damage causing early closure; the acetabular index improvement; and the
      age of the patient at time of operation. We assessed triradiate cartilage damage,
      a modified McKay clinical classification, acetabular index, center-edge angles,
      Reimers index, acetabular depth-to-width ratios, Severin classification and
      Tonnis grading of 33 patients (44 hips) have been evaluated in this retrospective
      study. The mean age at surgery was 5 years (range, 1.5-14 years). The minimum
      followup was 5 years (mean, 10.5 years; range, 5-17 years). Preoperatively, three
      (7%) hips were Tonnis Grade 2, 10 (23%) were Grade 3, and 31 (70%) were Grade 4.
      Eight (18%) hips were Severin Class 1, 32 (73%) Class 2, and four (9%) were Class
      3. According to McKay's criteria satisfactory results with a rate of 76% were
      obtained. Premature closure of the triradiate cartilage occurred in eight (18%)
      hips and postoperative avascular necrosis of the femoral head in three (6%) hips.
      Satisfactory clinical and radiographic improvements in the aforementioned
      parameters can be obtained by Pembersal osteotomy. LEVEL OF EVIDENCE: Level IV,
      therapeutic case series. See the Guidelines for Authors for a complete
      description of levels of evidence.

PMID- 18335300
TI  - No detectable major changes in gait analysis after soft tissue release in DDH.
AB  - The iliopsoas and adductor tendons are often soft tissue barriers obstructing
      relocation of the femoral head into the acetabulum and are frequently released to
      obtain reduction. We assessed whether posteromedial soft tissue release including
      sectioning of the adductor longus and iliopsoas tendons would lead to alterations
      in joint angles and moments of the hip joint or other major changes in the gait
      pattern. We conducted 3-D quantitative gait analysis of 10 patients (mean age,
      8.1 years) who had unilateral and surgically treated DDH before the age of 18
      months. The mean single support time was shorter in the unaffected side of the
      patients than in the healthy control group. Mean pelvic excursions in both
      frontal and sagittal planes and maximum knee extension at stance of the affected
      and unaffected sides were higher in the patients than in the control group. Peak
      hip flexion moment during swing phase was somewhat reduced, and the hip moment
      crossover point from extension to flexion was slightly delayed in both the
      affected and unaffected sides. We could not identify an explanation for the
      slight deviations due to limited data. However, sectioning of the adductor longus
      and iliopsoas tendons in DDH patients under 18 months old did not appear to lead
      to major objective clinical gait alterations. LEVEL OF EVIDENCE: Level II,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18335301
TI  - Endoscopy-assisted periacetabular osteotomy: a preliminary cadaveric study.
AB  - Periacetabular osteotomy has been recommended for reconstructing symptomatic
      dysplastic hips in adolescents and young adults, but requires substantial
      incisions and exposure. To minimize large incisions, we asked whether
      periacetabular osteotomy could be performed with a mini-incision under direct
      endoscopic control. We used five fresh-frozen cadaver pelves and developed curved
      guides and osteotomes for the osteotomy. We were able to perform a periacetabular
      osteotomy under endoscopic and image intensifier control and to fix the osteotomy
      with two cannulated screws. We identified no damage to vital structures or
      intraarticular fracture in any of the five cadavers we subsequently dissected. We
      believe periacetabular osteotomy may be performed with a mini-incision under
      direct endoscopic control. Our preliminary observations suggest the approach
      might be explored in limited prospective clinical trials by experienced
      individuals.

PMID- 18335302
TI  - Detection of polymolecular associations in hydrophobized chitosan derivatives
      using fluorescent probes.
AB  - The microenvironment formed by lauroyl and stearoyl derivatives of chitosan in
      solution has been studied using two fluorescent probes, pyrene and nabumetone.
      Existence or not of microdomains formed by polymolecular associations, the
      inherent hydrophobicity of them in aqueous solution, and the influence of degree
      of substitution (DS) of derivatives were investigated by emission properties of
      pyrene and strengthened by the photophysical behavior of nabumetone.
      Additionally, the ratio between the fluorescence intensities of first
      (approximately 372 nm) to the third (approximately 384 nm) bands of the emission
      spectrum of pyrene was used to determine the critical aggregation concentration
      (CAC). In a previous work, it was already reported the characterization of
      chitosan derivatives by three spectroscopic techniques ((13)C-NMR, (1)H-NMR and
      infrared), as well as data on the solubility and swelling-index of them. In
      addition of that, the new results show that the investigated lauroyl and stearoyl
      derivatives of chitosan are expected to be potential models for applications in
      the medical field.

PMID- 18335303
TI  - Fluorescence properties of dibenzofluorescein in aqueous solution.
AB  - The deprotonation of dibenzofluorescein (DBFL), a long wavelength fluorescence
      probe, results in the simultaneous occurrence of neutral form, monoanion and
      dianion under physiological conditions. The fluorescence properties of the former
      two cannot be measured directly because they are always coexistent with some
      other species. By measuring the fluorescence under various pHs we computed the
      fluorescence parameters for each species involved in the prototropic equilibria
      of DBFL, including each species' emission spectrum, excitation spectrum, emission
      and excitation maximum, fluorescence quantum yield and lifetime. It was found
      that the monoanion is the most fluorescent chromospheres (Phif=0.66, compared to
      Phif=0.25 for dianion, 0.18 for cation and 0.0 for the neutral form). Together
      with the computed pKas, we are able to suggest that the monoanion plays a major
      role under physiological conditions when DBFL is used as a fluorescence probe,
      contrary to the assumption in literature.

PMID- 18335304
TI  - Interaction among cadmium sulfide nanoparticles, acridine orange, and
      deoxyribonucleic acid in fluorescence spectra and a method for deoxyribonucleic
      acid determination.
AB  - Some studies on quantum dots (QD) as donors that enhance the fluorescence of a
      dye as an acceptor through fluorescence resonance energy transfer (FRET) have
      been reported. However, in the present work we discovered that CdS quantum dots
      sharply quenched the fluorescence of acridine orange (AO). Also, DNA enhanced the
      fluorescent signals of AO quenched by CdS. The extents of enhancement were in
      good proportion to the DNA concentrations. Based on this, a sensitive method was
      employed to determine DNA with both good selectivity and sensitivity. The
      calibration curve was linear over 60-4,000 ng mL(-1) and the determination limit
      (3sigma) was 4.39 ng mL(-1).

PMID- 18335305
TI  - Diagnostic trilemma: isorhythmic AV dissociation mimicking intermittent
      preexcitation and acute inferior myocardial infarction.
AB  - In this case report, we present a patient with intermittent isorhythmic
      atrioventricular dissociation mimicking two different electrocardiographic
      entities: ventricular preexcitation pattern and recurrent acute inferior
      myocardial infarction.

PMID- 18335306
TI  - Evaluation of the female sexual function index in a population based sample from
      Finland.
AB  - The factor structure and reliability of the Female Sexual Function Index (FSFI)
      was evaluated in a Finnish population based sample of 2,081 women, age 33-43
      years. In addition, associations between female sexual function and age,
      psychological distress, alcohol use, hormone based contraceptives, child sexual
      abuse (CSA), and adult sexual abuse were examined. The results supported a six
      factor solution for the FSFI with high internal consistencies, in line with
      earlier research in clinical populations. Psychological distress was positively
      associated with every dimension of the FSFI except desire problems. Age was
      associated with fewer pain problems. Alcohol use was associated with every
      dimension of the FSFI, but the direction of the association depended on if it was
      drinking in general or in connection to intercourse. More drinking in general was
      related to fewer sexual function problems while drinking in connection to
      intercourse was related to more sexual function problems. No significant
      correlation was found between adult sexual abuse and sexual function but between
      CSA and lubrication, satisfaction, and pain problems. Usage of oral contraceptive
      pill was not significantly associated with sexual function. The use of hormone
      based intrauterine systems was significantly associated with less pain and more
      desire, arousal, and satisfaction. In conclusion, the study supports use of the
      FSFI for assessing sexual function not only in clinical samples but also in
      population based samples. The associations found between sexual function and
      other important variables showed the complexity of sexual function.

PMID- 18335307
TI  - Peripherally presented emotional scenes: a spatiotemporal analysis of early ERP
      responses.
AB  - Recent findings from event-related potentials (ERPs) studies provided strong
      evidence that centrally presented emotional pictures could be used to assess
      affective processing. Moreover, several studies showed that emotionally charged
      stimuli may automatically attract attention even if these are not consciously
      identified. Indeed, such perceptive conditions can be compared to those typical
      of the peripheral vision, particularly known to have low spatial resolution
      capacities. The aim of the present study was to characterize at behavioral and
      neural levels the impact of emotional visual scenes presented in peripheral
      vision. Eighteen participants were asked to categorize neutral and unpleasant
      pictures presented at central (0 degrees ) and peripheral eccentricities (-30 and
      +30 degrees ) while ERPs were recorded from 63 electrodes. ERPs were analysed by
      means of spatio-temporal principal component analyses (PCA) in order to evaluate
      influences of the emotional content on ERP components for each spatial position
      (central vs. peripheral). Main results highlight that affective modulation of
      early ERP components exists for both centrally and peripherally presented
      pictures. These findings suggest that, for far peripheral eccentricities as for
      central vision, the brain engages specific resources to process emotional
      information.

PMID- 18335308
TI  - Motor commands of facial expressions: the bereitschaftspotential of posed smiles.
AB  - Electroencephalographic (EEG) premotor potentials with negative polarity like the
      Bereitschaftspotential (BP) are known to precede self-paced voluntary movements
      of the limbs and other body parts. This is however the first report of such
      premotor potentials before posed smiles. Scalp EEG was recorded in 16 healthy
      participants performing self-paced unilateral and bilateral smiles and unilateral
      finger movements. Amplitudes over six central electrodes and voltage
      distributions over the entire scalp were compared across conditions at time of
      EMG-onset, thus focusing on the late BP. Results show the presence of a premotor
      potential before posed smiles with a later onset, symmetrical bilateral
      distribution, and smaller amplitude at time of movement-onset, compared to finger
      movements. Future studies should investigate the BP before various types of
      emotional and non-emotional facial expressions.

PMID- 18335309
TI  - Affective prime and target picture processing: an ERP analysis of early and late
      interference effects.
AB  - Viewing emotionally arousing compared to neutral pictures is associated with
      differential electrophysiological activity in early ("early posterior
      negativity", EPN), as well as later time-windows ("late positive potential",
      LPP). A previous study revealed that the EPN is reduced when the preceding prime
      picture was emotional. The present study explored whether sequential interference
      effects are specific for early processing stages or extend to later processing
      stages. Dense sensor ERPs were measured while subjects viewed a continuous stream
      of pleasant, neutral, and unpleasant pictures, presented for 660 ms each.
      Previous results were replicated in that emotional pictures were associated with
      enlarged EPN and LPP amplitudes compared to neutral pictures. Furthermore, the
      EPN to emotional and neutral pictures was reduced when preceded by pleasant prime
      pictures. The novel finding was that emotional compared to neutral prime pictures
      were associated with reduced LPP amplitudes to the subsequently presented picture
      irrespective of its emotional valence (pleasant, neutral, unpleasant). These
      results demonstrate sustained interference effects in serial picture
      presentations discussed within a framework of resource competition among
      successive pictures.

PMID- 18335310
TI  - Neuromagnetic activity during recognition of emotional pictures.
AB  - Recently studied 'old' stimuli lead to larger frontal and parietal ERP responses
      than 'new' stimuli. The present experiment investigated the neuromagnetic
      correlates (MEG) of this 'old-new' effect and its modulation by emotional
      stimulus content. Highly arousing pleasant, highly arousing unpleasant and un
      arousing neutral photographs were presented to the participants with the
      instruction to memorize them. They were later re-presented together with new
      photographs in an old-new decision task. In line with previous ERP studies, a
      long-lasting old-new effect (350-700 ms) was found. Independently, an emotion
      effect also occurred, as reflected in a, particularly left temporal, activity
      increase for emotional pictures between 450 and 580 ms. Moreover, only for the
      pleasant pictures did the early part of the old-new effect, which is thought to
      reflect familiarity based recognition processes, interact with picture content:
      The old-new effect for pleasant pictures in frontal regions was larger than the
      one for neutral or unpleasant pictures between 350 and 450 ms. In parallel,
      subjects' responses were accelerated towards and biased in favour of classifying
      pleasant pictures as old. However, when false alarm rate was taken into account,
      there was no significant effect of emotional content on recognition accuracy. In
      sum, this MEG study demonstrates an effect of particularly pleasant emotional
      content on recognition memory which may be mediated by a familiarity based
      process.

PMID- 18335311
TI  - Protection of respiratory chain enzymes from ischaemic damage in adult rat brain
      slices.
AB  - The effect of aglycaemic hypoxia (AH) on the activity of the mitochondrial
      respiratory chain complexes was measured in superfused adult cortical brain
      slices. After 15 min of AH the activity of complex II-III was significantly
      reduced (by 45%) with no change in complex I or IV. Following 30 min of
      reperfusion the activities of complex II-III and IV were significantly reduced
      (by 45% and 20% respectively). These reductions in enzyme activity were abolished
      by removing the external calcium or by the addition of N omega-nitro-L-arginine
      (LNNA) or an analogue of superoxide dismutase (SOD) manganese [III] tetrakis 4
      benzoic acid porphyrin (Mn-TBAP). These data suggest that a reactive oxygen
      species (ROS) such as peroxynitrite is involved in the reduction of mitochondrial
      complex activities following AH.

PMID- 18335312
TI  - Localization of the extracellular matrix protein SC1 coincides with
      synaptogenesis during rat postnatal development.
AB  - SC1 is an extracellular matrix protein that belongs to the SPARC family of
      matricellular molecules. This anti-adhesive protein localizes to synapses in the
      adult rat brain and has been postulated to modulate synapse shape. In this study,
      increased levels of SC1 were detected from postnatal days 10-20, with a peak at
      postnatal day 15, a period of intense synaptogenesis. During this time, increased
      colocalization of SC1 with the synaptic marker synaptophysin was observed in
      synapse-rich regions of the cerebellum and the cerebral cortex. These findings
      indicate that the pattern of SC1 localization coincided with synaptogenesis
      during rat postnatal development.

PMID- 18335313
TI  - Effects of Abeta1-42 on the subunits of KATP expression in cultured primary rat
      basal forebrain neurons.
AB  - ATP-sensitive potassium channels (KATP) play a crucial role in coupling metabolic
      energy to the membrane potential of cells, thereby functioning as cellular
      "metabolic sensors." Recent evidence has showed a connection between the amyloid
      neurotoxic cascade and metabolic impairment. With regard to their neuroprotection
      in other neuronal preparations, KATP channels may mediate a potential
      neuroprotective role in Alzheimer's disease (AD). To investigate the effects of
      Abeta1-42 on the subunits of KATP expression in cultured primary rat basal
      forebrain cholinergic neurons, primary rat basal forebrain neurons were cultured
      and evaluated. The subunits of KATP: Kir6.1, Kir6.2, SUR1 and SUR2 expressing
      changes were observed by double immunofluorescence and immunoblotting when the
      neurons were exposed to Abeta1-42(2 microM) for different time (0, 24, 72 h). We
      found a significant increase in the expression of Kir6.1 and SUR2 in the cultured
      neurons being exposed to Abeta1-42 for 24 h, while Kir6.2 and SUR1 showed no
      significant change. However, after being treated with Abeta1-42 for 72 h, the
      expression of the four subunits was all increased significantly compared with the
      control. These findings suggest that being exposed to Abeta1-42 for different
      time (24 and 72 h) induces differential regulations of KATP subunits expression
      in cultured primary rat basal forebrain cholinergic neurons. The change in
      composition of KATP may contribute to resist the toxicity of Abeta1-42.

PMID- 18335314
TI  - Astrocytes protect against copper-catalysed loss of extracellular glutathione.
AB  - Glutathione (GSH) is one of the major antioxidants in the brain. GSH is secreted
      by astrocytes and this extracellular GSH is used by neurones to maintain and
      increase their intracellular GSH levels. For efficient GSH trafficking between
      astrocytes and neurones, GSH needs to be maintained in the reduced form. In model
      systems, GSH trafficking has been shown to be essential for neuroprotection
      against a variety of stress conditions. Previously we and others have shown that
      GSH and thiols are unstable in cell culture media and are easily oxidised. In the
      present study it is shown that nanomolar concentrations of copper (II) ions can
      cause decay of GSH in cell culture media. Increased free or redox active copper
      has been implicated in a variety of diseases and degradation of extracellular GSH
      is a possible mechanism by which it exerts its harmful effects. Rat astrocytes, a
      human astrocytoma cell line and astrocyte-conditioned media, in the absence of
      cells, are able to retard this copper-catalysed decay of GSH and maintain GSH in
      its reduced form. The protective effect of astrocytes appears to be a combination
      of copper removing and antioxidant mechanisms. The importance of these protective
      mechanisms is discussed with regards to neurodegenerative diseases.

PMID- 18335315
TI  - Daily intake of high dietary fiber slows accelerated colonic transit induced by
      restrain stress in rats.
AB  - BACKGROUND: Stress and central corticotropin releasing factor (CRF) are
      contributing factors to the pathogenesis of irritable bowel syndrome (IBS). It
      has been shown that restraint stress and central CRF stimulate colonic motility
      in rats. Short-chain fatty acids (SCFAs) are produced by bacterial fermentation
      from dietary fibers. It is controversial whether daily intake of dietary fiber is
      beneficial for patients with diarrhea-predominant IBS. We studied whether dietary
      fiber intake affects colonic transit and motility stimulated by restraint stress
      and central CRF in rats. METHODS: Corn starch is digested almost completely in
      the small intestine, while potato starch shows substantial resistance to alpha
      amylase and its consumption leads to stimulation of large-bowel fermentation.
      Four weeks after a corn starch, potato starch, or usual diet (rat chow), colonic
      transit and motility stimulated by restraint stress and intracisternal (ic)
      injection of CRF were studied. Fecal concentration of SCFAs in the cecum was
      measured by high-performance liquid chromatography (HPLC). RESULTS: Four-week
      treatment with potato starch diet significantly increased cecal concentrations of
      SCFAs, compared to treatment with corn starch diet. Accelerated colonic transit
      induced by stress and ic injection of CRF (1 microg) were significantly
      attenuated in rats receiving potato starch diet compared to rats receiving corn
      starch diet. The incidence of unformed stool (diarrhea) induced by stress and CRF
      was also reduced in rats receiving potato starch diet compared to rats receiving
      corn starch diet and usual diet. CONCLUSION: It is suggested that daily intake of
      a high-fiber diet may prevent stress- and CRF-induced acceleration of colonic
      transit and diarrhea. This study may contribute to treatment for the patients of
      diarrhea-predominant IBS.

PMID- 18335316
TI  - Hydrogel-based microsensors for wireless chemical monitoring.
AB  - We report fabrication and characterization of a new hydrogel-based microsensor
      for wireless chemical monitoring. The basic device structure is a high
      sensitivity capacitive pressure sensor coupled to a stimuli-sensitive hydrogel
      that is confined between a stiff porous membrane and a thin glass diaphragm. As
      small molecules pass through the porous membrane, the hydrogel swells and
      deflects the diaphragm which is also the movable plate of the variable capacitor
      in an LC resonator. The resulting change in resonant frequency can be remotely
      detected by the phase-dip technique. Prior to hydrogel loading, the sensitivity
      of the pressure sensor to applied air pressure was measured to be 222 kHz/kPa
      over the range of 41.9-51.1 MHz. With a pH-sensitive hydrogel, the sensor
      displayed a sensitivity of 1.16 MHz/pH for pH 3.0-6.5, and a response time of 45
      minutes.

PMID- 18335317
TI  - Single-cell tumor dormancy model of uveal melanoma.
AB  - BACKGROUND: Ocular melanoma is easily treated by the removal of the eye or
      through plaque radiotherapy. However, after removal or control of the primary
      tumor, patients can develop fatal liver metastases up to 20 years later. It has
      been reported that difficulties in imaging single cells and the propensity for
      tumor cells to replicate rapidly in animal models account for the deficit of
      single-cell tumor dormancy models. METHODS: In this paper, we performed two
      animal experiments using green fluorescent-labeled uveal melanoma cells in nude
      mice. Cells were injected via tail-vein and the experiments ran 20 and 42 days,
      respectively. Labeled cells were imaged in vivo via skin-flap and epifluorescent
      microscopy. RESULTS: The first experiment exemplified the feasibility of a single
      cell tumor dormancy model; cells were present in multiple organs post-injection,
      but persisted solely in the liver for the duration of the experiment. The second
      experiment, demonstrating the presence and viability of these single, metastatic
      seeds 6 weeks after injection. CONCLUSION: Due to the inherent difficulties in
      establishing single-celled tumor dormancy models, few exist. In this paper, we
      have successfully developed a single-cell dormancy model of uveal melanoma, a
      disease that, in patients, epitomizes tumor dormancy. This model has the
      potential to reveal the mechanisms behind dormancy, identify patients at high
      risk for metastatic development, and develop new serum biomarkers for
      micrometastasis detection.

PMID- 18335318
TI  - Surface electrodes are not sufficient to detect neurotonic discharges:
      observations in a porcine model and clinical review of deltoid electromyographic
      monitoring using multiple electrodes.
AB  - OBJECTIVE: In order to define the preferred electromyographic monitoring method
      during spine surgery, (1) a porcine model of neurotonic generation after lumbar
      root compression was developed and (2) intraoperative use of deltoid muscle
      intramuscular needle, subdermal needle, and surface electrodes was
      retrospectively reviewed. METHODS: In pigs, an array of intramuscular needle,
      subdermal needle, and surface electrode derivations was differentially amplified
      at identical gain and filter settings. Nerve root compression generated
      neurotonic discharges whose amplitudes were compared at each derivation.
      Clinically, 25 deltoid muscles in 13 patients were simultaneously monitored
      (during cervical spine surgery at the C4-C5 level) with surface, subdermal
      needle, and intramuscular needle electrode pairs, differentially amplified at
      identical gain and filter settings. Non-repeating neurotonic discharges were
      assigned, by amplitude and morphology, to best derivation (intramuscular,
      subdermal, surface or combination); coincident amplitudes were measured at the
      maximum deflection among the three derivations. Actual voltage detected between
      clinical methods was analyzed with Friedman's test and any detection versus none
      by general estimating equations(GEE) using SAS. The advantage of two needles over
      one in detection of any voltage was assessed using McNemar's test. RESULTS:
      Compressed porcine lumbar roots generated neurotonics which were identifiable at
      intramuscular sites only. Clinically, 31 neurotonics were identified: 20/31 at
      intramuscular, 5/31 at subdermal, and 6/31 equally well at intramuscular and
      subdermal derivations. Intramuscular detected neurotonics better than subdermal
      derivations (z = 2.9, P < .004). No voltage was recorded at the surface in 16/31
      neurotonics. For detection of any voltage, intramuscular was better than
      subdermal (z = -1.5, P = .04) or surface electrodes (z = -2.7, P < .001).
      CONCLUSIONS: Electromyographic moni- toring of spine surgery should not be done
      by surface electrodes. Because sensitive neurotonic detection requires near field
      recording, intramuscular electrodes are preferred. Monitoring of a myotome at
      particularly increased risk may suggest multiple intramuscular electrodes.

PMID- 18335319
TI  - Advances in concepts and methods for the marine environment: implications for
      policy.
AB  - Science-based indicators aimed at measuring the sustainability of human
      activities on the environment have become of prime importance in the policy
      arena. At the international level, the Commission on Sustainable Development and
      the Convention on Biological Diversity and other Multilateral Environmental
      Agreements have recognised the need to develop a set of scientific indicators
      related to changes in biodiversity and other environmental issues able to direct
      policy decisions. In the marine realm, the study of the effects of both 'top
      down' extractive activities such as fishing is more and more dealt with, in
      conjunction with 'bottom-up' activities such as nutrient loading and the effects
      on biogeochemical cycles, marine geochemistry and ecosystem structure and
      functioning of other pollutants and contaminants. 'Conventional' approaches such
      as the identification of taxa, model organisms and related methodologies will
      continue playing a key role for the monitoring of human-induced changes in the
      marine environment. On the other hand, newly developed disciplines such as
      genomics, proteomics and biodiversity informatics are increasingly looked at as a
      source of information and applications that can respond to questions and concerns
      by the policy community such as the need to adapt to global and climate change in
      the marine environment so as to mitigate its societal implications.

PMID- 18335320
TI  - Gene concepts and genethics: beyond exceptionalism.
AB  - The discursive explosion that was provoked by the new genetics could support the
      impression that the ethical and social problems posed by the new genetics are
      somehow exceptional in their very nature. According to this view we are faced
      with special ethical and social problems that create a challenge so fundamental
      that the special label of genethics is needless to justify. The historical
      account regarding the evolution of the gene concepts could serve us to highlight
      the limits of what we know about genes and what we can do with genes. The
      widespread notion about the exceptionality of genetic knowledge and its
      applicative possibilities is hardly justifiable and leads to misunderstandings
      regarding the conceptualization of the ethical and social problems we might face.
      Following a more realistic interpretation of the role of genes in human life we
      might avoid a whole set of fictive dilemmas and counterproductive regulatory
      efforts in bioethics. Bioethical discourse should move from the gene-centered
      scientific discourse toward the more sophisticated and complex discourses where
      human development represented as a matter of complex interactions between genomes
      and environments, between genes, educational factors, nutritional regimes, and
      other different developmental resources. If a gene is seen as one among the
      different developmental resources that are shaping a given human trait then both
      genethics and genetic exceptionalism could hardly be represented as a justified
      approach in discussing the ethical and social problems of genetics.

PMID- 18335322
TI  - Serum pro-inflammatory cytokines in physiological and pre-eclamptic pregnancies.
AB  - BACKGROUND: Pre-eclampsia is a heterogeneous syndrome ranging from mild
      hypertension and proteinuria to severe pre-eclampsia with complications, which
      can also be associated with an enhanced maternal inflammatory response. METHODS:
      Tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL
      6) and interferon-gamma (IFN-gamma) were evaluated by multiplexed sandwich enzyme
      linked immunosorbent assay in 14 pre-eclamptic women, 57 normotensive pregnant
      women (20 in the first, 20 in the second and 17 in the third trimester) and 21
      non-pregnant women. RESULTS: The concentration of serum TNF-alpha was lower than
      the sensitivity limit of the assay in all groups. The prevalence of measurable IL
      1 and IL-6 values, but not that of IFN-gamma, increased significantly in the
      second and third trimesters of pregnancy. However, the percentage of subjects
      with higher or detectable values of pro-inflammatory cytokines was statistically
      different between pre-eclamptic women and those in the second and third trimester
      of physiological pregnancy. CONCLUSIONS: Results of this study do not support
      standard screening for pro-inflammatory cytokines (TNF-alpha, IL-1, IL-6 and IFN
      gamma) in pre-eclampsia.

PMID- 18335321
TI  - Heat shock proteins in animal neoplasms and human tumours--a comparison.
AB  - Heat shock proteins (HSPs) are implicated in all phases of cancer from
      proliferation, impaired apoptosis and sustained angiogenesis to invasion and
      metastasis. The presence of abnormal HSP levels in several human tumours suggests
      that these proteins could be used as diagnostic and/or prognostic markers, whilst
      the direct correlation between HSP expression and drug resistance in neoplastic
      tissues means they could also be used to predict cancer response to specific
      treatment. HSPs have also been successfully targeted in clinical trials modifying
      their expression or chaperone activity. Preliminary studies in veterinary
      medicine have also demonstrated the presence of altered HSP expression in
      neoplasms, and the study of carcinogenesis and the role of HSPs in animal models
      will surely be an additional source of information for clinical cancer research.

PMID- 18335323
TI  - Serum insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, leptin
      concentrations and insulin resistance in benign and malignant epithelial ovarian
      tumors in postmenopausal women.
AB  - AIMS: The aims of the present study were to determine the serum concentrations of
      insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein
      3 (IGFBP-3) and leptin and insulin resistance in benign and malignant epithelial
      ovarian tumors, and to discuss the use of these markers in benign-malignant tumor
      differentiation. METHODS: Forty-seven postmenopausal women with ovarian tumor and
      31 age-matched, postmenopausal, healthy controls were included in this study.
      Insulin resistance index by homeostasis model assessment (HOMA score) and fasting
      blood glucose (FBG), serum IGF-I, IGFBP-3, leptin and CA-125 concentrations were
      determined in all patients preoperatively. The results were evaluated according
      to postoperative histopathology results. RESULTS: According to postoperative
      histopathology results, the patients were divided into malignant (n = 23), benign
      (n = 24) and control (n = 31) groups. There were no differences among the groups
      in relation to age, body mass index, FBG and HOMA score (p > 0.05). Serum
      concentrations of CA-125 were elevated in the malignant group compared with the
      benign ovarian tumor and control groups (p < 0.05). In contrast, serum IGF-I
      concentrations were significantly decreased in patients with malignant and benign
      ovarian tumors compared with controls (p < 0.05). Serum IGFBP-3 concentrations
      were also found to be lower in women with malignant ovarian tumors than in women
      with benign tumors (p < 0.05). Serum leptin did not differ among patients with
      malignant-benign tumors and controls (p > 0.05). CONCLUSION: Serum leptin and
      HOMA score have not been found to be valid indicators in ovarian tumors. However,
      the present data suggest that low concentrations of IGF-I and IGFBP-3 could be a
      reliable marker to differentiate benign from malignant ovarian tumors. Further
      experimental studies are warranted to understand the impact of the IGF-I system
      in ovarian carcinogenesis.

PMID- 18335325
TI  - The effect of oral contraceptives on aromatase expression in the eutopic
      endometrium of patients with endometriosis.
AB  - OBJECTIVE: To determine the effect of oral contraceptives containing gestodene on
      aromatase expression in the endometrium of patients diagnosed with endometriosis.
      PATIENTS AND METHODS: Endometrial biopsies were taken at the time of laparoscopy
      in 40 patients with endometriosis, 16 of whom were using an oral contraceptive
      containing gestodene at the time of laparoscopy. The remaining 24 patients were
      receiving no form of treatment for endometriosis. Endometrial biopsies taken from
      23 patients with normal echographic signs and no symptoms were used as controls.
      Aromatase expression was evaluated in endometrial samples using
      immunohistochemistry. RESULTS: In the untreated, symptomatic endometriosis
      patients, aromatase expression was detected during the proliferative phase in 92%
      of cases, while in the symptom-free control patients aromatase was expressed in
      only 9% of cases. In patients with endometriosis who were using oral
      contraceptives, there were significantly fewer cases of positive endometria
      compared with the untreated patients with endometriosis (6%). CONCLUSION: Oral
      contraceptives containing gestodene are effective in decreasing aromatase
      expression in the eutopic endometrium of patients with endometriosis.

PMID- 18335326
TI  - The World Health Organization defines hormone replacement therapy as
      carcinogenic: is this plausible?
AB  - In June 2005 the World Health Organization's International Agency for Research on
      Cancer (IARC) classified combined hormone contraception and menopausal therapy as
      carcinogenic in humans. The IARC's function is to identify potential carcinogens
      associated with nutrition, environment and pharmaceutical products. They do not
      produce risk-benefit analyses for any country or population. Their conclusions
      are highly controversial in that no proof is presented for a causal relationship
      of estrogens with reproductive cancer, be it plausibility according to mechanisms
      of action or experimental evidence in an animal model. Equating natural compounds
      like estradiol with defined carcinogens like asbestos, tobacco smoke as well as
      indispensable drugs such as aspirin and tamoxifen is of no substantial clinical
      relevance. Thus, there are no new reasons to change current management principles
      with combination hormone contraception and therapy.

PMID- 18335327
TI  - beta(3)-adrenergic receptor polymorphism and metabolic syndrome in postmenopausal
      women.
AB  - OBJECTIVES: Some studies indicate that the Trp64Arg polymorphism in the gene
      encoding the beta(3)-adrenergic receptor (ADRB3) is associated with obesity,
      insulin resistance and earlier onset of type 2 diabetes mellitus. The aim of the
      present study was to evaluate the frequency of ADRB3 polymorphism and its
      association with metabolic syndrome in postmenopausal women. METHODS: We
      performed the study on 284 randomly chosen postmenopausal women, aged 50-60
      years, who were then selected to the study. Measurements of anthropometric
      parameters and biochemical estimations such as lipid profile, glucose and insulin
      level in serum were carried out using commercial kits. ADRB3 genotyping was
      performed by polymerase chain reaction and mini-sequencing. RESULTS: The
      frequency of the Trp64/Arg64 genotype in the investigated population was 13%, and
      of the Trp64/Trp64 genotype, 85%. The Arg64/Arg64 genotype was present in only 2%
      of women. Metabolic syndrome was recognized in 22% of women bearing Trp64/Arg64
      genotype and in 14% of women bearing Trp64/Trp64 genotype, without a
      statistically significant difference between the two groups (p > 0.05 in the
      chi(2) test). Women bearing the Trp64/Arg64 genotype had lower serum levels of
      high-density lipoprotein cholesterol (HDL-C) than Trp64/Trp64 genotype women
      (63.2 +/- 13.0 vs. 71.4 +/- 17.4 mg/dl). Both groups did not differ in any other
      investigated parameter. CONCLUSION: Trp64Arg polymorphism of the beta(3)
      adrenergic receptor gene is not related to metabolic syndrome in postmenopausal
      Polish women; however, it seems to be associated with decreased HDL-C levels.

PMID- 18335328
TI  - Myo-inositol administration positively affects hyperinsulinemia and hormonal
      parameters in overweight patients with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate the effects the administration of myo-inositol (MYO) on
      hormonal parameters in a group of PCOS patients. DESIGN: Controlled clinical
      study. SETTING: PCOS patients in a clinical research environment. PATIENTS: 20
      overweight PCOS patients were enrolled after informed consent. INTERVENTIONS: All
      patients underwent hormonal evaluations and an oral glucose tollerance test
      (OGTT) before and after 12 weeks of therapy (Group A (n = 10): myo-inositol 2 gr.
      plus folic acid 200 mug every day; Group B (n = 10): folic acid 200 mug every
      day). Ultrasound examinations and Ferriman-Gallwey score were also performed.
      MAIN OUTCOME MEASURES: Plasma LH, FSH, PRL, E2, 17OHP, A, T, glucose, insulin, C
      peptide concentrations, BMI, HOMA index and glucose-to-insulin ratio. RESULTS:
      After 12 weeks of MYO administration plasma LH, PRL, T, insulin levels and LH/FSH
      resulted significantly reduced. Insulin sensitivity, expressed as glucose-to
      insulin ratio and HOMA index resulted significantly improved after 12 weeks of
      treatment. Menstrual cyclicity was restored in all amenorrheic and
      oligomenorrheic subjects. No changes occurred in the patients treated with folic
      acid. CONCLUSIONS: Myo-inositol administration improves reproductive axis
      functioning in PCOS patients reducing the hyperinsulinemic state that affects LH
      secretion.

PMID- 18335329
TI  - A comparison of the effects of clomiphene citrate and the aromatase inhibitor
      letrozole on superovulation in Asian women with normal ovulatory cycles.
AB  - OBJECTIVE: To compare the effect of the aromatase inhibitor letrozole and
      clomiphene citrate (CC) on superovulation in women with normal ovulation.
      METHODS: A cross-over randomized study of 22 women with normal ovulation, divided
      randomly into two equal cohorts, was carried out. Each group of 11 women was
      randomly allocated to take letrozole or CC for one cycle. After washing out for
      one cycle, the alternative drug was administered in the subsequent cycle. The
      number and size of mature follicles, endometrial thickness, and estradiol and
      progesterone levels were monitored. RESULTS: The number of mature follicles and
      estradiol levels on ovulation day were significantly lower in the letrozole group
      than the CC group (p < 0.05 for both). However, no differences between the two
      groups in endometrial thickness and pattern were observed. Progesterone levels
      showed ovulation in all cycles. CONCLUSIONS: The administration of 50 mg CC on
      days 3-5 was superior to 2.5 mg letrozole for superovulation induction in women
      with normal ovulation.

PMID- 18335330
TI  - A steroid-cell tumor of the ovary resulting in massive androgen excess early in
      the gonadol steroidogenic pathway.
AB  - We describe the case of a 35-year-old woman with an ovarian steroid-cell tumor
      secreting markedly elevated levels of testosterone (28.3 nmol/l),
      dehydroepiandrosterone sulfate (19.7 mumol/l), androstenedione (>34.7 nmol/l) and
      17-hydroxyprogesterone (100.5 nmol/l) into plasma. We could find no report within
      the literature of androgens at the levels described in this patient. Herein we
      review the literature and discuss the possible endocrine etiology of the excess
      androgens observed in this case. We also discuss the differential diagnosis,
      investigation and interpretation of androgens of adrenal and ovarian origin.

PMID- 18335331
TI  - Prevalence of nonclassic adrenal hyperplasia (NCAH) in hyperandrogenic women.
AB  - OBJECTIVE: The clinical symptoms of nonclassic adrenal hyperplasia (NCAH) are
      identical with polycystic ovary syndrome (PCOS). The aim of our study was to
      determine the prevalence of nonclassic adrenal hyperplasia (21-hydroxylase
      deficiency) in hyperandrogenic women, its biochemical, endocrine and clinical
      characteristics and to compare them with parameters of patients with ovarian
      hyperandrogenism. METHODS: Since 1999, 298 patients with elevation of at least
      one androgen and manifestation of one of the clinical androgenic symptoms
      (oligo/amenorrhea, hirsutism or acne) have been identified in our database. A
      diagnosis of NCAH was considered when the basal or stimulated 17
      hydroxyprogesterone was elevated. RESULTS: Only eight patients were identified as
      having 21- hydroxylase deficient NCAH in the whole group of 298 hyperandrogenic
      women. Hirsutism and acne were found only in three, two patients, five of them
      had oligo/amenorrhea. Seven patients had both elevated basal and stimulated 17
      hydroxyprogesterone, while in one case only elevation of stimulated level was
      found. All of the NCAH patients had elevated concentrations of testosterone, six
      DHEA, lower SHBG was found in four patients. Surprisingly, none of the NCAH
      patients had increased DHEAS. CONCLUSION: In our study, the prevalence of NCAH in
      hyperandrogenic women was 2.68%. Their leading symptom was oligomenorrhea, skin
      androgenic disorders were a minor clinical problem. None of the NCAH patients had
      an elevated DHEAS, the androgen dominantly produced by the adrenal glands.

PMID- 18335332
TI  - Pharmacological investigations of the unique herbal formula Menoprogen in rats:
      estrogenic activity and mechanism.
AB  - The present study aimed to evaluate the pharmacological effects of Menoprogen in
      the management of menopausal symptoms for aged female rats. Menoprogen was
      supplemented to a group of elderly female rats for 8 weeks. Subsequently,
      histopathological examinations were conducted in the isolated uterine and ovary
      tissues and pituitary glands of the rats. Serum levels of estradiol (E(2)),
      progesterone (P), follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
      were determined. The ultrastructure of the rat ovarian granulocytes was analyzed.
      The histopathological examinations revealed no statistical difference in the
      quantity of follicles in the ovary and of acidophil and basophil cells in the
      anterior pituitary gland of the Menoprogen-fed rats versus healthy normal rats.
      Moreover, the cellular morphogenesis was in a healthy state for the Menoprogen
      fed rats. Menoprogen significantly increased the levels of serum E(2) and P but
      reduced FSH and LH levels. The electron microscopic analysis showed that
      Menoprogen significantly retarded apoptosis of the ovarian granulocytes of the
      rats. Further investigation of Menoprogen for the alternative treatment of
      menopausal symptoms is warranted.

PMID- 18335333
TI  - A spontaneous and severe case of ovarian hyperstimulation syndrome after
      delivery.
AB  - Ovarian hyperstimulation syndrome (OHSS) is almost exclusively associated with
      ovulation induction with gonadotropins or, occasionally, clomiphene citrate.
      Severe ovarian hyperstimulation after delivery has never been reported
      previously. Herein we report a case of OHSS after delivery by Cesarean section.
      The left ovary was subjected to wedge section and three-quarters of the tissue
      was removed. A cyst on the right ovary was enucleated and fluid within the cysts
      was sucked away. The patient was treated by intravenous albumin infusion.

PMID- 18335334
TI  - Oxalates in some Indian green leafy vegetables.
AB  - The soluble and total oxalate contents of 11 leafy vegetables grown in India were
      determined. Spinach, purple and green amaranth and colocasia contained high
      levels of total oxalates, which ranged from 5,138.0 +/- 37.6 mg/100 g dry matter
      up to 12,576.1 +/- 107.9 mg/100 g dry matter. Seven other leafy vegetables
      (curry, drumstick, shepu, fenugreek, coriander, radish and onion stalks)
      contained only insoluble oxalate, which ranged from 209.0 +/- 5.0 mg/100 g dry
      matter to 2,774.9 +/-18.4 mg/100 g dry matter. In vitro digestion of the samples
      showed that the gastric available oxalate was 10% lower than the values obtained
      from acid extraction and that intestinal available oxalate was 20% lower than the
      values obtained following hot water extraction. The percentage calcium bound in
      the insoluble oxalate fraction of the dried leafy vegetables ranged from 3.3% to
      86.7% of the total calcium. Addition of four different sources of calcium (low
      fat milk, whole milk, calcium carbonate and calcium sulphate) resulted in a range
      of 32-100% reductions of intestinal available oxalate in the mixture.

PMID- 18335335
TI  - Two new compounds from Ixeris sonchifolia.
AB  - Two new compounds, named as sonchifolactone E (1) and sonchifolinin B (2), have
      been isolated from the whole plant of Ixeris sonchifolia, along with one known
      compound, sonchifolatone A (3). Their structures and stereochemistry were
      determined by spectroscopic methods.

PMID- 18335336
TI  - Speciosaperoxide, a new triterpene acid, and other terpenoids from Chaenomeles
      speciosa.
AB  - Investigation on the EtOH extract of the fruits of Chaenomeles speciosa led to
      the isolation of a new triterpene acid bearing an unusual hydroperoxyl substitute
      group at C-11, speciosaperoxide (1), along with six known triterpenoids, 3beta
      acetoxyurs-11-en-13beta,28-olide (2), 3-O-acetyl ursolic acid (3), oleanolic acid
      (4), ursolic acid (5), masilinic acid (6), and tormentic acid (7), and three
      known norsesquiterpenoids, roseoside (8), vomifoliol (9) and (6S,7E,9R)-6,9
      dihydroxy-4,7-megastigmadien-3-one 9-O-[beta-d-xylopyranosyl (1 --> 6)
      glucopyranoside] (10). Their structures were elucidated on the basis of
      spectroscopic data and comparison with reference data. Besides compound 1,
      compounds 2, 8-10 were obtained from this genus for the first time. None of these
      compounds exhibited inhibitory activity against T-and B-lymphocyte proliferation.

PMID- 18335337
TI  - Anti-hepatotoxic activity of cichotyboside, a sesquiterpene glycoside from the
      seeds of Cichorium intybus.
AB  - The seeds of Cichorium intybus L. (Asteraceae) afforded a new guaianolide
      sesquiterpene glycoside, cichotyboside, which was characterized as 2alpha, 6beta,
      7beta, 15-tetrahydroxy-1 (10), 4 (5)-diene-guaian-9alpha, 12-olide-7-O-beta
      caffoyl-15-O-beta-D-glucoside (1) by means of spectral methods. Cichotyboside (1)
      exhibited a significant anti-hepatotoxic activity against CCl4 induced toxicity
      in Wistar rats, wherein it reduced the elevated levels of liver enzymes such as
      serum glutamate oxaloacetate transaminase (SGOT) by 52 units/ml; SGPT 38
      units/ml; ALKP 24.97 units/ml and 7.54 g/dl, 5.48 g/dl increase in total protein
      and albumin, respectively. It was observed that cichotyboside (1) decreased the
      level of ALKP comparable with that of standard drug silymarin, exhibiting an 88%
      decrease in comparison to silymarin (92%) and increased the level of total
      albumin 85% in comparison to silymarin (89%) against intoxicated control.
      Whereas, the levels of SGOT and SGPT were also decreased considerably in
      comparison to standard and intoxicated control.

PMID- 18335338
TI  - One new bufadienolide from Chinese drug "Chan'Su".
AB  - A new bufadienolide named 16beta-acetoxy-bufarenogin (1), together with six known
      bufadienolides, namely, 11alpha,12beta-dihydroxy-bufalin (2), bufotalin (3),
      hellebrigenin (4), desacetylbufotalin (5), gamabufotalin (6), and resibufagin (7)
      were isolated from Chan'Su. Of these, 2 was a new natural product. Their
      structures were elucidated by spectral methods. The cytotoxic activities in vitro
      of these compounds have been assayed against HeLa cell line. They all showed
      strong cytotoxic activities.

PMID- 18335339
TI  - Three new lignan glycosides from Mananthes patentiflora.
AB  - Three new lignan glycosides, mananthosides I-K (1-3), were isolated from the
      ethanolic extract of the aerial part of Mananthes patentiflora. The structure
      elucidation of these compounds was mainly established on the basis of 1D NMR, 2D
      NMR and HR-MS spectroscopic analysis.

PMID- 18335340
TI  - Ether-soluble resin glycosides from the roots of Ipomoea batatas.
AB  - Two new resin glycosides, batataosides I (1) and II (2), and five known
      compounds, friedelin (3), scopoletin (4), octadecyl caffeate (5), beta
      sistosterol (6) and daucosterol (7), were isolated from the roots of Ipomoea
      batatas. Their structures have been determined based on the chemical and spectral
      data. Batataosides I and II have novel structures because the core simonic acid B
      was esterised with cinnamic acid for the first time, and three different
      substituent esterification groups in one resin glycoside is scarce. The absolute
      configuration of the aglycone was elucidated to be S by Mosher's method.

PMID- 18335341
TI  - Brominated derivatives from the Chinese sponge Pseudoceratina sp.
AB  - Chemical examination of the marine sponge Pseudoceratina sp. resulted in the
      isolation and characterization of two new dibromotyrosine-derived metabolites (1
      2), and a new histamine-derived alkaloid (3), along with eight known
      dibromotyrosine based products. Their structures were elucidated on the basis of
      IR, 1D and 2D NMR, and MS spectral data analyses.

PMID- 18335342
TI  - Three new triterpenoid saponins from the seeds of Aesculus turbinata.
AB  - Three new triterpenoid saponins, named isoescins VIIa (1), VIa (2), and VIIIa
      (3), were isolated from the seeds of Aesculus turbinata and identified by
      spectroscopic analysis and chemical hydrolysis. Their structures were established
      as 21beta-O-tigloyl-28-O-acetylprotoaescigenin 3beta-O-[beta-d-galactopyranosyl(1
      --> 2)][beta-d-glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid
      (Isoescin VIIa, 1), 21beta-O-(2-methylbutyryl)-28-O-acetylprotoaescigenin 3beta-O
      [beta-d-glucopyranosyl(1 --> 2)] [beta-d-glucopyranosyl(1 --> 4)]-beta-d
      glucopyranosiduronic acid (Isoescin VIa, 2), and 21beta-O-angeloyl-28-O
      acetylbarringtogenol C 3beta-O-[beta-d-glucopyranosyl(1 --> 2)] [beta-d
      glucopyranosyl(1 --> 4)]-beta-d-glucopyranosiduronic acid (Isoescin VIIIa, 3).

PMID- 18335343
TI  - Two new compounds from Cynanchum amplexicaule.
AB  - A new phenolic glycoside, sinapic acid 4-O-beta-d-(6'-sinapoyl)glucopyranoside
      (1) and a new sucrose ester, 6,6'-di-O-sinapoylsurcose (3), were isolated from
      the roots of Cynanchum amplexicaule (Sieb. et Zucc.), along with two known
      compounds, 6-O-[E]-sinapoyl-d-glucopyranoside (2) and sibricose A1 (4). Their
      structures were elucidated on the basis of both chemical and spectroscopic
      methods.

PMID- 18335344
TI  - A potent anti-HIV polyphenol from Salvia yunnanensis.
AB  - A new polyphenol, designated as salvianolic acid N, was isolated from the aqueous
      extracts of the roots of Salvia yunnanensis. Its chemical structure was
      elucidated as 3-(3,4-dihydroxylphenyl)-2-[(E)-3-(1,8,9-trihydroxyl
      dibenzo[b,f]oxpin-3-yl)acryloxloxy]propanoic acid (1) on the basis of NMR and MS
      spectral analyses. The new polyphenol inhibited both HIV-1 IN in vitro and also
      reduced HIV-1 p24 antigen in MT-4 cell lines.

PMID- 18335345
TI  - Two new prenylated coumarins from Spiranthes sinensis (Pers.) Ames.
AB  - Two new prenylated coumarins, sinensins A and B, have been isolated from the
      roots of Spiranthes sinensis (Pers.) Ames. Their structures were elucidated as 5
      gamma, gamma-dimethylallyl-8-[2-(2,6-dihydroxyphenyl)-3-dimethyl-but-2-enyol]
      umbelliferon (1) and 4,6-di(gamma, gamma-dimethylallyl)-8-lavandulyl-umbelliferon
      (2) on the basis of spectroscopic analysis.

PMID- 18335346
TI  - Two new triterpenoid saponins from the carpophore of Xanthoceras sorbifolia
      Bunge.
AB  - Two new triterpenoid saponins (1, 2) and a known sapogenin (3) were isolated from
      the dried carpophore of Xanthoceras sorbifolia Bunge. (Sapindaceae), and their
      structures were established as 3-O-beta-d-glucopyranosyl, 28-O-[alpha-l-rhamnosyl
      (1 --> 2)]-beta-d-glucopyranosyl 16-deoxybarrin-gtogenol C (1), 3-O-[beta-d
      glucopyranosyl(1 --> 6)] 3'-angeloyl)-beta-d-glucopyranosyl, 28-O-[alpha-l
      rhamnosyl(1 --> 2)]-beta-d-glucopyranosyl 16-deoxybarringtogenol C (2), 16
      deoxybarringtogenol C (3), by spectral and chemical methods. Compounds 1 and 2
      were found to have activity of inhibiting the proliferation of two human tumour
      cell lines while compound 3 was inactive.

PMID- 18335347
TI  - Triterpene saponins from Lysimachia christinae.
AB  - Seven triterpene saponins were isolated from Lysimachia christinae and identified
      as lysichriside A (1), lysichriside B (2), primulanin (3), lysikokianoside 1 (4),
      anagallisin C (5), ardisiacrispin A (6), and ardisicrenoside B (7). Compounds 1
      and 2 are new triterpene saponins, compounds 3, 5, and 7 were isolated from this
      genus, and compounds 4 and 6 were isolated from this species for the first time.
      Their structures were elucidated by means of 1D and 2D NMR experiments.

PMID- 18335349
TI  - Thermal effect of illumination on microsurgical transfer of free flaps:
      experimental study and clinical implications.
AB  - The light source of a modern operating microscope gives a clear operative field,
      but the possibility of thermal impairment by the strong light is substantial. We
      aimed to elucidate the potential risk of such strong light on transfer of free
      flaps and the optimal application of light. First, the thermal effect of
      clinically used microsurgical illumination was examined by direct irradiation of
      a thermometer. Secondly, the thermal influence on living tissue of microsurgical
      light was evaluated using a model of vascularised and non-vascularised pedicled
      groin flaps in rats. Thirdly, the influence of strong light on the transfer of
      free flaps was investigated using a model of a free groin flap in rats. Fourthly,
      histological alteration was investigated by a light microscopy and scanning
      electron microscopy. With direct irradiation of a thermometer, temperatures
      reached values in excess of 80 degrees C with maximal xenon light illumination
      from 20 cm. The mode of illumination significantly influenced the results of free
      flaps. Prolonged irradiation of the vascular pedicle in particular resulted in an
      increase in the number of failures, supposedly caused by venous occlusion. Bright
      illumination contributed to efficient microvascular procedures, but we confirmed
      its potential risk. Our findings may benefit all surgeons engaged in transfer of
      free flaps, as potential impairment caused by excessive operative irradiation is
      prevented simply by recognition of its harm.

PMID- 18335350
TI  - von Langenbeck procedures at 8 months or Wardill at 18 months for primary repair
      of cleft palate in adult Swedish patients with unilateral complete cleft lip and
      palate: a study of facial growth.
AB  - The purpose of this study was to compare facial growth in patients with
      unilateral complete cleft lip and palate (UCLP) in whom the palate was repaired
      with the von Langenbeck procedure at 8 months (L-8), or the Wardill procedure at
      18 months (W-18). A total of 151 unaffected subjects were used as a reference
      series. Sixty-one adult patients, 34 in the L-8 group and 27 in the W-18 group,
      were investigated clinically and with lateral skull radiography and also filled
      out a questionnaire about their dental condition. Multiple linear regression was
      used to analyse the effects of the surgical strategy, sex, and the presence of a
      velopharyngeal flap on several dependent variables indicating sagittal jaw
      relations, vertical jaw relations, and inclination of incisors. The UCLP group
      was characterised by a short (n-sp) and retrusive maxilla (s-n-ss) and a
      retrusive mandible for women (s-n-sm), larger maxillary inclination (NSL/NL),
      more retroclined lower incisors (IL(I)/ML), shorter upper facial heights (n-sp)
      and normal total face height (n-gn) than the reference group. In the UCLP group
      there were significant differences between men and women in mandibular
      prognathism (s-n-sm), maxillary/mandibular relations (ss-n-sm), maxillary
      inclination (NSL/NL), total anterior facial height (n-gn), and upper anterior
      facial height (n-sp). Lateral crossbite was found in 20% of the UCLP group. The
      prevalence was similar in the L-8 and W-18 groups. Almost 80% of the patients in
      the UCLP group considered that their dental condition was good. The choice of
      surgical strategy had no significant influence on the variables measured on
      facial morphology.

PMID- 18335351
TI  - Survival and function in patients with tumours of the head and neck operated on
      and reconstructed with free flaps.
AB  - From 1983 to 2003, 131 patients were operated on in the head and neck region with
      139 free flaps. They were operated on using a team approach of ear, nose, and
      throat surgeons and plastic surgeons, and sometimes maxillofacial surgeons. The
      tumours were squamous cell carcinoma (SCC) 104 (80%), salivary gland cancer 13
      (10%), sarcoma 5 (4%), basal cell carcinoma 4 (3%), and others 4 (3%). The
      staging of the primary intraoral SCC tumours (n=79) was 42% in stage II, 28% in
      stage III, and 30% in stage IV. The survival of patients with primary oral SCC
      was compared with a previously treated previous series that gave an increase in
      tumour-related five-year survival from 48% to 58%. Most flaps were radial forearm
      flaps (73%). Fifteen percent were vascularised bone transfers. A questionnaire
      was sent to patients who had had oral/oropharyngeal tumours to measure function
      and satisfaction, to which 47/49 responded. The results including ability to chew
      and swallow; speech was good, with a median score of 0.78 (range 1-0).

PMID- 18335352
TI  - Management of haemangiomas of infancy: a retrospective analysis and a treatment
      protocol.
AB  - Haemangiomas of infancy are common benign endothelial neoplasms that affect
      roughly 1:10 children. Treatment is indicated in complicated cases. We have
      evaluated treatment in a multidisciplinary setting. The charts of all affected
      patients between 1985 and 2000 were reviewed. The personal details,
      complications, indications for treatment, and outcome, were evaluated. Treatment
      was started in 77 of the 282 cases reviewed. Ulceration and bleeding were the
      most common complications and were successfully treated when indicated in 29/39
      patients (74%) with wound dressings and antibiotics. Systemic steroids were given
      to 18 patients, usually for block of the visual fields and respiratory
      impairment. A good or moderate result was obtained in 16/18 patients. Twelve
      patients required operation. Based on our results and those of others, we propose
      a protocol for treatment.

PMID- 18335353
TI  - Incomplete excision of basal cell carcinoma in the subunits of the nose.
AB  - Reconstructive procedures after resection of nasal basal cell carcinoma (BCC)
      vary depending on the subunit involved. The aim of the present study was to
      assess the influence of the location of the BCC on the rate of incomplete
      excisions, so we made a retrospective analysis of all nasal BCC excised at our
      hospital between 2002 and 2005. The incomplete excision rate was 24/148 (16%).
      More incomplete excision occurred on the alae (n=13) when compared to the dorsum
      (n=2) of the nose (p<0.05). Eight two-staged procedures resulted in incomplete
      resection, whereas 9 (6%) frozen section analyses were false-negative. BCC were
      most likely to be incompletely excised on the nasal tip and alae, and both
      subunits required more elaborate reconstructions. This, however, was not the
      result of poor estimation of the extent of the tumour and reluctance to excise
      more challenging areas widely for reconstruction, but to the method chosen to
      eradicate the tumour.

PMID- 18335354
TI  - Miniabdominoplasty for the treatment of aesthetic defects after Pfannenstiel
      incisions.
AB  - We describe the miniabdominoplasty technique adopted in patients with
      unfavourable aesthetic defects after Pfannenstiel incisions and give our results
      from 32 patients. Eligibility criteria were cutaneous ptosis after Pfannenstiel
      incisions, and skin elastic enough to do the miniabdominoplasty. Exclusion
      criteria were obese or previously fat subjects in whom the operation was not
      possible. The technique is based on the combination of a miniabdominoplasty done
      obliquely up to the fascia, and liposuction. We operated on 32 patients from
      September 2005 to May 2006. We saw no postoperative bleeding, haematoma, or
      seroma. Thirty-one patients had a good final result. In one case postoperative
      asymmetry required secondary remodelling, which was done under local anaesthesia
      as an outpatient. After six months follow-up we recorded no asymmetry or change
      in body shape. We use the miniabdominoplasty technique for the correction of
      cosmetic abnormalities after Pfannenstiel incisions. It is feasible and safe,
      with a short operating time, and gives good aesthetic results and few
      postoperative complications. Further studies, with more patients, are now
      required to validate these results.

PMID- 18335355
TI  - Testicular prosthetic implants in boys and teenagers with primary or secondary
      anorchism.
AB  - From 1989 to 2005, 13 patients aged between 5 and 18 years had testicular
      prostheses implanted at the Department of Plastic and Reconstructive Surgery,
      University Hospital, Malmo, Sweden. The most common indication for surgery was
      aplastic or vanishing testes. In 13 patients and 19 operations 7 unilateral and
      12 bilateral testicular prostheses were implanted. Each prosthesis was implanted
      through an inguinal skin incision, inserted digitally, and fixed with purse
      string sutures. Some years after the primary implant three of the patients have
      had a second operation in which the small prosthesis was exchanged for an adult
      one. There was only one minor postoperative complication, a superficial wound
      infection. No patient required reoperation. All patients were happy with the
      results of surgery at the follow-up. We recommend this operation for implantation
      of testicular prostheses.

PMID- 18335356
TI  - Suspected case of primary malignant melanoma of the parotid gland.
AB  - A patient presented with malignant melanoma of the parotid gland with no obvious
      primary lesions, which was treated by total parotidectomy with excision of skin.
      Despite radiotherapy for brain metastases and combination chemotherapy for lung
      and lymph node metastases, she died 13 months after the initial operation.

PMID- 18335357
TI  - Chest wall deformity after tissue expansion.
AB  - There have been few reports about skeletal changes beneath a tissue expander in
      breast reconstruction. We present one, and surgeons should be cautious about the
      possibility of skeletal deformities in patients who are osteoporotic and
      postmenopausal who require prolonged tissue expansion.

PMID- 18335358
TI  - Mirror therapy in a patient with a fractured wrist and no active wrist extension.
AB  - We report a patient in whom mirror therapy, training moving both hands while
      watching the reflection of the present or good hand in a parasaggital mirror - a
      method used for phantom limb and stroke patients - was extremely useful after a
      fractured wrist with good passive, but no active, extension.

PMID- 18335359
TI  - 'Governance of' and 'Governance by': implementing a clinical governance framework
      in an area mental health service.
AB  - OBJECTIVE: A framework developed to promote the understanding and application of
      clinical governance principles in an area mental health service is described. The
      framework is operationalized through systems, processes, roles and
      responsibilities. METHODS: The development of an explicit and operationalizable
      framework for clinical governance arose from the authors' experiences in leading
      and managing mental health services. There is a particular emphasis on
      improvement of quality of care and patient safety. The framework is informed by
      recent developments in thinking about clinical governance, including key
      documents from Australia and the United Kingdom. RESULTS: The operational nature
      of the framework allows for key components of clinical governance to be described
      explicitly, communicated effectively, and continually tested and improved.
      Further consideration and assessment of the value of differing approaches to this
      task are required. For example, a general, illustrative approach to raise
      clinician awareness can be contrasted with prescriptive and specified approaches
      which progressively encompass the many functions and processes of a mental health
      service. CONCLUSIONS: Mental health clinicians and managers can be guided by a
      framework that will ensure safe, high quality and continually improving processes
      of care.

PMID- 18335360
TI  - An outline of the planned work of the Royal Australian and New Zealand College of
      Psychiatrists' Board of Education.
AB  - OBJECTIVE: The aim of this paper is to inform College Fellows, trainees and other
      stakeholders about the structure, principles and functioning of the new Board of
      Education. CONCLUSION: The educational activities of the College are likely to
      evolve and to be developed over the next 5 years by a process taking account of
      the views of key stakeholders. In the short term, there will be no changes to
      training or examination processes which would disadvantage trainees.

PMID- 18335361
TI  - Pre-pubertal paediatric bipolar disorder: a controversy from America.
AB  - OBJECTIVE: The aim of this paper was to explore the rapid rise in the diagnosis
      of bipolar disorder (BD) in the paediatric, particularly pre-pubertal, age group,
      in the USA over the past decade and to look at associated controversies.
      CONCLUSIONS: There has been a very marked rise in the diagnosis of BD among pre
      pubertal children, and to a lesser extent adolescents, in the USA since the mid
      1990s. The rise appears to have been driven by a reconceptualizing of clusters of
      emotional and behavioural symptoms in the paediatric age group by some academic
      child psychiatry departments, most notably in St Louis, Boston and Cincinnati.
      There is controversy in both the academic literature and public media centring on
      diagnostic methods, epidemiological studies, adverse effects of medication
      including media-reported fatalities, and pharmaceutical company influence. With
      some exceptions, the traditional view of BD as being very rare prior to puberty
      and uncommon in adolescence appears accepted beyond the USA, though whether this
      is changing is as yet uncertain, and thus there are implications for Australian
      and New Zealand child and adolescent psychiatry.

PMID- 18335363
TI  - A cross-sectional survey of the frequency and characteristics of delusions in
      acute psychiatric wards.
AB  - OBJECTIVE: The aim of this paper was to ascertain the frequency and
      characteristics of delusions across several acute psychiatric wards. METHOD: A
      survey of the files of all 160 acute psychiatric inpatients aged 18-65 years
      within Western Sydney was conducted. Patients recorded as currently delusional
      were compared to non-delusional psychotic patients on demographic data,
      diagnoses, reason for admission, mode of admission, length of hospital stay,
      legal status, and treatments. RESULTS: More than one-half of all patients in the
      acute psychiatric wards were recorded as being delusional. Persecutory delusions
      were found in 80% of delusional patients, and multiple delusions were common.
      Most delusions were steady in course, and 40% lasted longer than 6 months.
      Patients with delusions received a diagnosis of schizophrenia in 67% of the
      cases, while 72% of patients with schizophrenia were recorded as having
      delusions. Almost 90% of delusional patients were detained involuntarily.
      Antipsychotic medications were the mainstay of treatment for delusional patients,
      and 30% were treated with more than one antipsychotic. Non-pharmacological
      strategies for managing delusions were not used. CONCLUSIONS: Delusions are
      commonly seen in acute psychiatric wards. There may be a relationship between the
      presence of delusions, severity of illness and treatment resistance. This
      highlights the need for a broad and more effective approach to management.

PMID- 18335364
TI  - Implementing smoke-free policies in mental health inpatient units: learning from
      unsuccessful experience.
AB  - OBJECTIVE: The aim of this paper is to describe the introduction, trial and
      termination of a smoke-free policy in an acute mental health unit of a regional
      hospital, and to consider factors that may contribute to the success of such
      policies in other settings. METHODS: This analysis is based on key informant
      interviews and review of correspondence related to the trial, and examination of
      the relevant incident-reporting database. RESULTS: Planning for implementation is
      described. The trial itself was terminated after 6 weeks due to perceived
      increases in aggression by patients towards staff working in the high dependency
      unit. Staff perceived that these episodes were directly related to these patients
      not being allowed to smoke. While there was an increase in events during the
      trial relating to two seriously ill individuals, examination of formal incident
      reports over a period of 2 years suggests little change in the overall number of
      incidents. CONCLUSIONS: Despite clear public health benefits, implementation of a
      smoke-free policy may have untoward behavioural effects in institutional mental
      health settings. In addition, staff expectations and perceptions are critical.
      Salient factors appear to be preparation of staff and patients, appropriate
      training, avoidance of exceptions and inconsistency, considering alternatives to
      smoking to fill the gap created by the policy, and a culture of critical
      evaluation in practice. Such processes will facilitate understanding and
      cooperation so that mental health services are able to participate in important
      policy processes with implications for the health of patients and staff.

PMID- 18335365
TI  - Motivations for self-injury in an adolescent inpatient population: development of
      a self-report measure.
AB  - OBJECTIVE: The aim of this study was to develop and pilot an instrument for the
      assessment of self-injury in adolescent inpatients. METHODS: The Self-Injury
      Motivation Scale was modified for use in adolescents. Thirty-eight consenting
      adolescent inpatients with a history of self-injury completed the Self-Injury
      Motivation Scale-Adolescent version (SIMS-A) and the Self-Injury Interview (SII)
      to collect information about a range of factors associated with self-injury,
      other clinical variables and demographic details. RESULTS: The SIMS-A was
      acceptable to this adolescent sample and motivations for self-injury were similar
      to those of adults using the original SIMS scale. Adolescents were, however, more
      likely to use self-injury for communicating to/influencing others compared to
      adults. The participants most frequently reported self-injury by hitting, cutting
      and burning. The clinical diagnosis most frequently associated with self-injury
      was major depression. Females reported earlier onset, higher frequency and
      multiple methods of self-injury compared to males. Distraction from emotional
      pain was the most common motivation for self-injury in both males and females.
      CONCLUSIONS: This pilot study suggests the SIMS-A is a useful self-report measure
      to assist clinicians and adolescent patients to understand a behaviour that may
      be associated with shame, guilt or other difficult emotions for the adolescent.
      Results also support the contention that there are often multiple and conflicting
      motivations for self-injury. Self-injury in this population was more common and
      severe in female adolescents compared to males, while clinical depression was a
      risk factor for self-injury in both males and females. The small sample size of
      adolescent inpatients is an important limitation of this pilot study, and
      research using the SIMS-A in larger samples is warranted.

PMID- 18335366
TI  - Psychiatry's problem child: PTSD in the forensic context: (part 1).
AB  - OBJECTIVE: The aim of this paper was to consider some of the recent literature
      that has raised questions about the prevalence of, and problems with, post
      traumatic stress disorder (PTSD) in the forensic context and whether it is a
      failure by experts to consider adequately Criterion A (1), which leads them into
      error and results in a skewed picture of the prevalence of PTSD in litigation.
      METHOD: The nature of the stressor criterion for PTSD from DSM-III to DSM-IV-TR,
      and recent literature relating to problems with the manner in which that stressor
      criterion is applied in forensic contexts, are considered. RESULTS: It becomes
      clear that, notwithstanding that the class of persons who can suffer PTSD after a
      particularly traumatic event has widened since it was included in the DSM-III,
      the nature of the stressor required before a diagnosis of PTSD can be made has
      remained fairly constant. CONCLUSIONS: Whether it is because PTSD is commonly
      associated with receiving a benefit (e.g. through post-war disability benefits,
      victims of crime compensation or because of a desire to use it as an ideological
      weapon), PTSD has become a ubiquitous presence in the forensic context,
      notwithstanding objective (i.e. non-forensic) clinical studies which refer to its
      rarity. It is clear now that PTSD symptoms can be readily simulated when the
      simulator is seeking a benefit. It is also becoming clear that some psychiatrists
      are not being as rigorous in the forensic context as they might be in a clinical
      context. Thus, with discussion now underway regarding DSM-V, it may be timely to
      reconsider the utility of PTSD as a clinical condition.

PMID- 18335367
TI  - Psychiatry's problem child: PTSD in the forensic context (part 2).
AB  - OBJECTIVE: The aim of this paper was to consider whether the Courts in their
      application of Criterion A for post-traumatic stress disorder (PTSD) in the civil
      forensic context are in harmony or in conflict with psychiatry. METHOD: Discussed
      are five cases from the civil forensic jurisdiction that considered plaintiffs'
      submissions that, as a consequence of some wrong, they suffered PTSD. RESULTS:
      The Courts have been quite consistent in their approach to PTSD--where there has
      been conflicting expert evidence as to whether a plaintiff has PTSD, the stressor
      which brings about this disorder must be extreme (i.e. objectively life
      threatening). CONCLUSIONS: The Courts have been consistent in their application
      of Criterion A and, as such, are consistent with what the DSM-IV-TR requires
      before the diagnosis can be made. Such an approach ensures that merely unpleasant
      events, irrespective of how subjectively upsetting they may be, do not qualify
      for the diagnosis of PTSD. Psychiatrists, therefore, have an enormous
      responsibility when they provide expert evidence in relation to psychiatric
      issues that arise in legal matters.

PMID- 18335368
TI  - Are Australian men with psychosis spending more time homeless?
AB  - OBJECTIVE: The objective of this study was to determine if homeless men with
      psychosis using emergency accommodation services are spending more time homeless.
      METHOD: A 12-month accommodation history was collected from all men with
      psychosis referred to mental health services using two emergency accommodation
      services in inner Melbourne over a 5-year period. RESULTS: Of the 241 men
      referred with psychosis, 200 (81%) were able to provide a full accommodation
      history. In 2001 the mean total days spent in crisis accommodation was 27.0 days
      and in 2005 the mean number of days was 60.9. Over the 5 years, increasing time
      was spent homeless in the 12 months prior to assessment, most commonly in
      emergency accommodations. CONCLUSIONS: Australian men with psychosis using
      emergency accommodation are spending an increasing amount of time homeless.

PMID- 18335369
TI  - First-episode psychosis in rural, coastal and remote Australian communities.
AB  - OBJECTIVE: The aim of this study was to investigate access to care and service
      delivery for first-episode psychosis (FEP) in rural, coastal and remote regions.
      METHOD: Routine clinical outcome data were analysed for patients aged 10-25 years
      who presented to mental health services in either a rural, coastal or remote
      region of New South Wales over a 3-year period. RESULTS: The results showed rural
      region FEP patients travelled significantly further to access services than non
      FEP patients. Remote region FEP patients were older and more likely to be male
      and Aboriginal than non-FEP patients. Alcohol and drug problems were
      significantly more likely for FEP than non-FEP patients across all regions.
      Utilization of mental health services was more frequent for FEP than non-FEP
      children and adolescents. CONCLUSION: The study highlights the importance of
      identification of FEP, particularly in the 10-18-year age group, where cognitive
      problems are likely to adversely affect schooling as well as be detrimental to
      social relationships. Service provision for FEP youth in rural areas requires
      innovation and coordination of limited resources, including better provision of
      training and ongoing clinical supervision.

PMID- 18335370
TI  - Acute treatment response and its predictors in patients with first-episode
      psychosis in Iran.
AB  - OBJECTIVE: The aim of this paper was to investigate the acute treatment response
      and its predictors in a sample of patients with first-episode psychosis admitted
      to a psychiatric hospital in Iran. METHOD: A total of 163 patients with first
      episode psychosis were treated with antipsychotics and other medications as
      prescribed by their treating psychiatrists. Sociodemographic and premorbid data
      at baseline and clinical data at both baseline and discharge (6+/-1 weeks after
      admission) were collected. RESULTS: Patients showed a response rate of 71.4% for
      negative symptoms, 91.5% for positive symptoms and 67.5% for functioning. Those
      having a positive family history and less severe negative symptoms at baseline
      were less likely to respond in terms of negative symptoms. Higher premorbid and
      lower baseline functioning as well as acute onset were associated with the
      treatment response. CONCLUSIONS: Acute treatment response of first-episode
      psychosis in a clinical sample of a developing country seems to be higher than
      that of developed countries. However, predictors of response are comparable.

PMID- 18335372
TI  - The 'youth model' in mental health services.

PMID- 18335379
TI  - [Long-term outcome for very preterm neonates].

PMID- 18335381
TI  - [Advances and restraints in cardiology].

PMID- 18335382
TI  - [Predictive value of NT-pro-BNP for the non-cardiologist. A study on 573
      hospitalized patients with cardiovascular disease].
AB  - BACKGROUND: B-type natriuretic peptides are excellent markers of cardiac function
      and are strong prognostic parameters in patients with coronary heart disease and
      heart failure. We examined the diagnostic and prognostic value of natriuretic
      peptides in a heterogeneous group of patients of a cardiological university
      hospital. METHODS: NT-pro-BNP was assessed in 573 inpatients (66 % male, median
      age 66 years) and association with demographic and cardiological parameters, in
      hospital course as well as the combined endpoint of death, heart failure
      hospitalization and stroke was analyzed during a median follow-up time of 1117
      days. RESULTS: NT-pro-BNP was significantly associated with age, diastolic blood
      pressure, renal function, previous myocardial infarction, arterial occlusive
      disease, atrial fibrillation, NYHA class and left-ventricular dysfunction.
      Differentiation of distinct cardiac diseases by NT-pro-BNP was not possible. NT
      pro-BNP identified patients with a length of hospital stay of more than 12 days
      with a sensitivity of 88,2 % and a negative predictive value of 97 %. Supramedian
      NT-pro-BNP values (> 300 pg/ml) indicated a relative risk for the combined
      endpoint of 7,5 (95 % CI 4,1 - 13,8) compared to inframedian NT-pro-BNP values.
      Prognostic value of NT-pro-BNP was independent of and stronger than demographic
      and cardiological risk markers. CONCLUSION: NT-pro-BNP is a strong and
      independent predictor of in-hospital course and long-term outcome in inpatients
      with cardiovascular disease. NT-pro-BNP assessment allows a risk-adapted patient
      management for non-cardiologists.

PMID- 18335383
TI  - [Surgical treatment of the hypereosinophilic syndrome with cardiac involvement
      (Loffler's endocarditis)].
AB  - HISTORY AND LABORATORY FINDINGS: A 38-year-old woman presented for further
      treatment of heart failure with NYHA class III symptoms and the idiopathic
      eosinophilia syndrome. Differential blood count had previously revealed an
      eosinophilia of 19%, which had fallen to normal under immunosuppression .
      INVESTIGATIONS: Echocardiography demonstrated echo-rich material in the left
      ventricular (LV) apex, severe mitral regurgitation and a restriction pattern in
      the transmitral flow profile. Magnetic resonance imaging (MRI) additionally
      showed a parietal thrombus sitting on the echo-rich mass in the LV apex.
      TREATMENT AND COURSE: Surgical LV endocardial resection and allogenic mitral
      valve replacement were performed. At follow-up (currently four years after the
      operation) the patient reported marked improvement of symptoms. Echocardiography
      and MRI demonstrated a normal configuration of the LV apex. CONCLUSION: While
      endomyocardial fibrosis usually has a poor prognosis, this case illustrates hat
      surgical treatment of an associated mitral regurgitation can in selected cases be
      successful.

PMID- 18335384
TI  - [Pace-maker syndrome].

PMID- 18335385
TI  - [The clotting system in the reperfused coronary circulation].

PMID- 18335386
TI  - [Coronary artery stenosis 2008: what are the indications for surgery?].

PMID- 18335387
TI  - [Coronary artery stenosis 2008: what are the indications for stent implantation
      and what kind of stent?].

PMID- 18335388
TI  - [Acute intervention for ST-segment elevation myocardial infarction (STEMI):
      treatment in Germany].

PMID- 18335389
TI  - [Acute intervention for ST-segment elevation myocardial infarction (STEMI):
      treatment in Europe].

PMID- 18335390
TI  - [Pathophysiology of myocardial reperfusion injury].
AB  - Rapid interventional restoration of coronary blood flow is the most effective
      therapy to limit infarct size in today}s cardiology. The early phase of
      reperfusion represents, however, a window of therapeutic opportunities largely
      unused in the clinic. Experimentally it has been clearly shown that the
      modalities of reperfusion have a substantial impact on infarct size, since
      reperfusion itself can damage the myocardium (reperfusion injury). The major
      cause for acute injury of the cardiomyocytes in reperfusion is their
      hypercontracture. Cytosolic Ca (2+) overload and malfunction of cell organelles,
      i. e. sarcoplasmic reticulum and mitochondria, determine the pathophysiology of
      reperfusion injury. The underlying mechanisms can be influenced in the first
      minutes of reperfusion by activation of protective signalling pathways
      (reperfusion therapy). First clinical studies confirm the efficacy of acute
      reperfusion therapy.

PMID- 18335391
TI  - [Cardiological options for acute protection of the reperfused myocardium].

PMID- 18335392
TI  - [The procedure of echocardiographic tests].

PMID- 18335393
TI  - A comparison of the levels of hepatocyte growth factor in serum in patients with
      type 1 diabetes mellitus with different stages of diabetic retinopathy.
AB  - INTRODUCTION: The aim of this study was to evaluate the blood concentration of
      hepatocyte growth factor (HGF) in patients at various stages of retinopathy. We
      hypothesised that the high level of HGF found in diabetic patients may be an
      important marker of retinopathy progression and that HGF level may be an index of
      the risk of proliferative retinopathy. MATERIAL AND METHODS: The participants in
      the study were 76 patients with type 1 diabetes mellitus. Of these, 35 patients
      were without retinopathy and formed Group 1. Of the remaining 41 patients with
      retinopathy, 20 patients had non-proliferative diabetic retinopathy (NPDR) and
      formed Group 2, while 21 patients had proliferative diabetic retinopathy (PDR)
      and formed Group 3. We evaluated the concentration of HGF In the peripheral blood
      by an enzyme-linked immunosorbent assay. RESULTS: Mean serum concentrations of
      HGF in the control group were significantly lower than in the type 1 diabetic
      patients. We found a significant increase in HGF serum concentrations in diabetic
      patients with PDR compared with the control group. Mean serum HGF concentrations
      were significantly higher in diabetic subjects with PDR than in diabetic patients
      without retinopathy. CONCLUSION: HGF concentration is increased in patients with
      type 1 diabetes mellitus with proliferative retinopathy, and concentrations
      increase with the progression of retinopathy, suggesting that HGF plays a role in
      the pathogenesis of proliferative diabetic retinopathy.

PMID- 18335394
TI  - [The possibility of prevention of type 2 diabetes].
AB  - INTRODUCTION: The aim of this study was to examine usefulness of oral glucose
      tolerance test (OGTT) in clinical evaluation of different glucose metabolism
      disturbances in subjects with at least one risk factor of type 2 diabetes. We
      compared the effectiveness of non-pharmacological and pharmacological prevention
      and treatment regiments on metabolic control in these individuals. MATERIAL AND
      METHODS: The study involved 130 patients, with the following characteristics: age
      between 18 to 76 years, mean body mass index (BMI) - 31.82 +/- 7.24 kg/m(2), and
      presence of at least one of the risk factor of type 2 diabetes. Glucose
      metabolism disturbances were diagnosed according to World Health Organization
      (WHO) criteria. Non-pharmacological regiments were applied for 3 months for
      patients with impaired glucose tolerance (IGT) and type 2 diabetes. Patients,
      whose still met criteria for type 2 diabetes during OGTT after non
      pharmacological treatment were scheduled for pharmacological interventions. These
      patients were assigned at random to two groups, that were treated with either
      metformin or acarbose. The measurements of total cholesterol (TC), HDL
      cholesterol , LDL-cholesterol, trigliceryde (TG), glucose, HbA(1c) and/or OGGT
      were performed during each visit. We also assessed risk factors for type 2
      diabetes in these subjects. RESULTS: The prevalence of abnormal glucose tolerance
      in subjects with at least one of the risk factor of diabetes type 2 was near 40%.
      OGTT in these subjects increased the possibility of diagnosis diabetes type 2 and
      IGT. Hypertension (81%), hypercholesterolemia (71.4%), hypertriglicerydemia
      (71.4%) and obesity (66.7%) were the most frequent risk factors observed. There
      were no differences in biochemical measurements between these groups of patients.
      CONCLUSIONS: Individuals with at least one risk factor of type 2 diabetes should
      have screening test to diagnose glucose intolerance. Both non-pharmacological and
      pharmacological intervention was effective in normalization of glucose OGTT in
      patients with diabetes type 2 and IGT in newly diagnosed with disease patients.

PMID- 18335395
TI  - The effect of weight loss on inflammation in obese women with polycystic ovary
      syndrome.
AB  - INTRODUCTION: The aim of the present study was to evaluate the effect of modest
      weight reduction on serum concentrations of tumour necrosis factor alpha (TNF
      alpha), TNF soluble receptors (sTNFRs) and interleukin-6 (IL-6) in obese women
      with polycystic ovary syndrome (PCOS). MATERIAL AND METHODS: The study group
      consisted of 15 obese women with PCOS (mean age 28.5 +/- 7.7 years). Serum
      concentrations of TNF-alpha, sTNFRs and IL-6, insulin, FSH, LH, DHEAS,
      androstendione, total and free testosterone, cortisol, 17OH-progesterone,
      oestradiol and sex hormone binding globulin (SHBG), glucose, total cholesterol,
      HDL cholesterol and triglycerides were measured before treatment and after 10%
      weight loss. All patients were advised to follow a 1000-1200 kcal diet with a
      limited intake of simple carbohydrate and animal fats and to exercise regularly
      (30 min, 3 times a week). Body composition was measured by bioimpedance. Serum
      concentrations of TNF-alpha, sTNFRs and IL-6 were determined by enzyme linked
      immunosorbent assay (ELISA). Plasma insulin, FSH, LH, DHEAS, androstendione,
      total and free testosterone, cortisol, 17OH-progesterone, oestradiol and SHBG
      were measured by a commercial RIA. Blood glucose, total cholesterol, HDL
      cholesterol and triglycerides were measured by an enzymatic procedure. RESULTS:
      We observed no differences in serum concentrations of TNF-alpha, sTNFRs or IL-6
      after treatment. CONCLUSIONS: It seems that more than a modest weight reduction
      is necessary to obtain a decrease in serum concentrations of proinflammatory
      cytokines and an improvement in ovarian function in obese women with polycystic
      ovary syndrome.

PMID- 18335396
TI  - The effect of weight loss on serum concentrations of FAS and tumour necrosis
      factor alpha in obese women.
AB  - INTRODUCTION: Apoptosis can influence both adipose tissue mass and its
      distribution. The suprafamily of tumour necrosis factor (TNF) receptors stimulate
      apoptosis. The aim of the study was to assess serum concentrations of tumour
      necrosis factor alpha (TNF-alpha), TNF soluble receptors (sTNFRs) and FAS in
      obese subjects and to examine the changes in these parameters after weight loss.
      MATERIAL AND METHODS: The study group consisted of 23 obese women without
      additional disease aged 36.6 +/- 10.9 years. These were examined before and after
      three-month weight reduction treatment consisting of a diet of 1000 kcal/day and
      physical exercise. The control group comprised 17 lean healthy women aged 40.3 +/
      5.5 years. Blood samples were taken in the morning after an overnight fast.
      Serum concentrations of TNF-alpha, sTNFRs and FAS were measured by enzyme linked
      immunosorbent assay (ELISA). Serum concentrations of insulin were measured by
      RIA. Serum concentrations of glucose, total cholesterol, HDL cholesterol and
      triglycerides were measured by an enzymatic procedure. RESULTS: The mean weight
      loss over the three-month treatment was 11.4 +/- 3.1 kg. Following weight loss,
      serum TNF-alpha concentrations decreased significantly (7.3 +/- 3.0 vs. 5.4 +/-
      1.6 pg/ml; p < 0.005) and concentrations of sTNFRs increased significantly
      (1222.6 +/- 211.8 vs. 1325.6 +/- 261.6 pg/ml; p < 0.05 and 1881.5 +/- 337.2 vs.
      2057.4 +/- 358.7 pg/ml; p < 0.05 respectively). However, no changes in serum
      concentrations of FAS were observed after weight loss. CONCLUSION: We observed
      increased serum concentrations of TNF-alpha but not of FAS in obese women. The
      concentrations of TNF decreased and those of sTNFRs increased after weight loss.
      However, the weight reduction therapy did not change serum concentrations of FAS.

PMID- 18335397
TI  - [Dispositional optimism and acceptance of illness among a group of individuals
      with Graves-Basedow's disease].
AB  - INTRODUCTION: Dispositional optimism is a general tendency to positively perceive
      the world and one's own future. We can consider what kind of connection with
      ability to cope with difficulties. One situation which is very stressful for an
      individual is an illness, particularly a chronic one. The aim of the paper was to
      define the connection between dispositional optimism and acceptance of illness
      among the group with Graves-Basedow disease. This is autoimmunizational illness
      and diseases of this kind are particularly sensitive to the influence of
      psychological factors, as there are many connections between the immune system
      and the human psyche. MATERIAL AND METHODS: The study group consisted of 59
      individuals with Graves-Basedow disease, 50 women and 9 men and 55 of healthy
      ones, 49 women and 6 men according to age, sex and a level of education. The
      patients filled out three psychological questionnaires: The Life Orientation Test
      Revised (LOT-R), The Acceptance of Illness Scale (AIS) and The Personal
      Questionnaire. RESULTS: of the study in question indicate a lack of differences
      between individuals with Graves-Basedow disease and healthy ones concerning the
      level of dispositional optimism. There no differences in the level of
      dispositional optimism as regards of criterion of health: by the levels of
      hormones TSH, fT3 and fT4, complications and a time of duration of disease.
      Instead, if they suffer additionally from others diseases, they have a lower
      level of dispositional optimism. There exist a connection between intensification
      of level of dispositional optimism and acceptance of illness among testing group.
      CONCLUSIONS: The dispositional optimism as a supply of individual helps her or
      his in adaptation to difficulty situation, which is a chronic disease. It is a
      reason way it is worth to help of patients to grow it stronger.

PMID- 18335398
TI  - [The main reasons behind variability in detection of prolactin and causes of true
      or apparent discordance with clinical state].
AB  - Both the "hook" effect and macroprolactinaemia, are the main reasons behind the
      discrepancy of serum prolactin level results in various laboratories. They can
      cause the diagnostic dilemmas or even completely faulty diagnosis resulting with
      undertaking of unnecessary investigations and/or an inappropriate method of
      treatment. Therefore, a review article on this matters may be of some help for
      clinical practice.

PMID- 18335399
TI  - [Acquired von Willebrand's disease in the course of severe primary hypothyroidism
      in a patient with autoimmune polyglandular syndrome type 3].
AB  - The case of a 20-year old female, who had been followed because of von Willebrand
      disease (vWD) was presented in this paper . She had a past history of menorrhagia
      and bleeding after dental procedures and the activity of von Willebrand factor
      (vWF) was decreased. Because of suggestive clinical features, the workup for
      hypothyroidism was performed and the patient was found to have severe
      hypothyroidism due to Hashimoto thyroiditis. After the institution of replacement
      therapy with levothyroxine, von Willebrand factor activity returned to normal
      range and symptoms of von Willebrand disease disappeared. Based on these
      findings, the diagnosis of acquired von Willebrand syndrome (AvWS) due to
      hypothyroidism was made. The development of myasthenia led to the final diagnosis
      of autoimmune polyglandular syndrome type 3 (APS) with myasthenia gravis and
      vitiligo.

PMID- 18335400
TI  - [Diagnostic and therapeutic guidelines for gastrointestinal neuroendocrine tumors
      (recommended by the Polish Network of Neuroendocrine Tumors)].
AB  - We have recently observed an increased interest in gastro-entero-pancreatic
      neuroendocrine tumors (GEP NET). They are rare cancer types and therefore
      collaborative effort of specialists in various disciplines of medicine is
      necessary to work out the diagnostic and therapeutic guidelines. In this
      publication we present general guidelines of the Polish Network of Neuroendocrine
      Tumors for the management of patients with GEP NET, developed at the Round Table
      Conference which took place in Kliczkow near Wroclaw in November 2007. In the
      subsequent parts of this publication, we present the rules of diagnostic and
      therapeutic management of: - endocrine tumors of the stomach and duodenum
      (including gastrinoma); - pancreatic endocrine tumors; - neuroendocrine tumors of
      the small intestine and the appendix; - neuroendocrine tumors of the colon. We
      hope that the proposed guidelines by Polish and foreign experts representing
      various disciplines of medicine, including endocrinology, gastroenterology,
      surgery, oncology, nuclear medicine and pathomorphology, will become a useful
      tool in the diagnostics and treatment of these patients.

PMID- 18335401
TI  - [Endocrine tumors of the stomach and duodenum (including gastrinoma) - management
      guidelines (recommended by the Polish Network of Neuroendocrine Tumors)].
AB  - The neuroendocrine tumors of the stomach and duodenum constitute only minority of
      neoplasms in this localisation. However due to their clinical behaviour and/or
      hormonal syndromes they pose diagnostic and therapeutic challenge. They display
      distinct phenotypes, regarding their pathogenesis, pathology and clinical course.
      Herein we present Polish guidelines for biochemical, pathological and
      localisation diagnosis, and discuss therapeutic approaches, considering
      endoscopic and surgical treatment, pharmacological and radionuclide therapy.

PMID- 18335402
TI  - [Pancreatic endocrine tumors - management guidelines (recommended by the Polish
      Network of Neuroendocrine Tumors)].
AB  - Pancreatic endocrine tumors (PETs) are rare neoplasms of this organ. The majority
      of PETs are tumors without hormonal activity. In this publication, we present the
      diagnostic and therapeutic guidelines for the management of these tumors proposed
      by the Polish Network of Neuroendocrine Tumors. These guidelines refer to
      biochemical and location diagnostics, including scintygraphy of somatostatin
      receptors, endoscopic ultrasonography and other anatomical and functional imaging
      methods. High importance is attached to correct histopathological diagnosis which
      determines further management of patients with PETs. Antitumor therapy requires
      multidirectional procedure, and therefore the rules of surgical treatment,
      biotherapy, chemotherapy and peptide receptor radionuclide therapy are discussed.

PMID- 18335403
TI  - [Neuroendocrine tumors of the small intestine and the appendix - management
      guidelines (recommended by The Polish Network of Neuroendocrine Tumors)].
AB  - Polish recommendations regarding management of patients suffering from
      neuroendocrine tumors of small intestine and appendix are presented. Small
      intestine, especially ileum represent most common origin of these tumors.
      Majority of them are well differentiated and grow slowly. Rarely, they are less
      differentiated with fast growth and poor prognosis. Symptoms are atypical,
      diagnosis could be often accidental. In 4-10% of patients typical symptoms of
      carcinoid syndrome are present. Chromogranin A is useful in the laboratory
      diagnostics, and urinary excretion of 5-hydroxyindoloacetic acid is helpful for
      the diagnostics and monitoring of the disease. Histopathological diagnostics was
      extensively described. Ultrasound, colonoscopy, capsule endoscopy, baloon
      enteroscopy, computed tomography, magnetic resonance and somatostatin analogs
      scintigraphy could be used for the visualization. The treatment of choice in the
      neuroendocrine tumors of small intestine and appendix is radical or palliative
      surgery, if possible using endoscopy. Pharmacotherapy consists of biotherapy and
      chemotherapy. The crucial in biotherapy is somatostatin analogs application,
      possible in symptomatic treatment of hormonally functioning tumors. This is
      treatment of choice in carcinoid crisis. Interferon alfa could be applied because
      of the same indications as somatostatin analogs, except for carcinoid crisis.
      Chemotherapy is less successful in disseminated or locally advanced intestinal
      neuroendocrine tumors, so radioisotope therapy should be considered in each case
      of unresectable tumor.

PMID- 18335404
TI  - [Neuroendocrine tumors of the colon - management guidelines (recommended by The
      Polish Network of Neuroendocrine Tumors)].
AB  - The neuroendocrine tumors (NET) of the colon are rare with a rising incidence due
      to an increased number of diagnostic examination including screening colonoscopy.
      According to distinct prognosis and treatment these tumors are classified as
      colonic or rectal NET. This paper provides the consensus guidelines for
      management of patients with these neoplasms recommended by the Polish
      Neuroendocrine Tumor Network Group. Furthermore the epidemiology and clinical
      presentation are described.

PMID- 18335406
TI  - The structure of acquired aural cholesteatoma as revealed by scanning electron
      microscopy.
AB  - The structural features of cells, their surfaces and the extracellular matrix
      were investigated in acquired aural cholesteatoma. Cholesteatomas surgically
      removed from 30 patients were examined by a scanning electron microscope (SEM).
      The predominant part of a cholesteatoma was composed of stratified squamous
      epithelium, showing extensive chaotic desquamation. The surface sculpture of the
      keratinocytes and corneocytes varied from parallel ridges, irregular microplicae
      and mirovilli, to flat grooves and pits and a completely smooth surface.
      Sheetlike lamellar structures, probably representing an intercellular lipid
      forming permeability barrier, were also observed. Small crystals located in the
      perimatrix were observed in one case. According to the SEM observations,
      cholesteatoma epithelium is characterised by abnormal and uncoordinated
      keratinisation, with a predominance of the advanced stages of the process.

PMID- 18335407
TI  - Myostatin and its precursor protein are increased in the skeletal muscle of
      patients with Type-II muscle fibre atrophy.
AB  - Preferential atrophy of Type-II muscle fibres occurs in several clinical
      situations, including cachexia, muscle disuse, chronic glucocorticoid treatment,
      remote neoplasia, and sometimes as an aspect of recent-denervation. For the
      patient, the Type-II atrophy itself might be unfavourable (as a glucocorticoid
      side-effect) or favourable (survivalistic via the muscle-alanine liver
      gluconeogenesis pathway in starvation). The cellular mechanisms underlying Type
      II fibre atrophy are unclear. Myostatin (Mstn) is physiologically a negative
      regulator of muscle mass and strength. In this study we evaluated a possible role
      of Mstn in Type-II fibre atrophy in human muscle. Mstn and Mstn precursor protein
      (MstnPP) were studied in 10-muscle biopsies containing Type-II fibre atrophy and
      in 17 disease and normal control muscle biopsies. When comparison was made with
      normal control fibres, we found the following: 1) by immunocytochemistry,
      diffusely increased Mstn/MstnPP in the atrophic Type-II muscle fibres; 2) by
      immunoblots, Mstn/MstnPP increased individually; 3) by RT-PCR, no increase in
      MstnPP mRNA. In conclusion, our results a) suggest that Mstn/ /MstnPP might play
      a role in the pathogenic cascade of Type-II muscle fibre atrophy; b) broaden our
      previously-described associations of Mstn in human muscle pathology, and c) could
      possibly lead to clinical prevention when Type-II muscle fibre atrophy is
      unfavourable, for instance in glucocorticoid therapy.

PMID- 18335408
TI  - Early trabeculation and closure of the interventricular foramen in staged human
      embryos.
AB  - Internal differentiation of the ventricles was studied in staged serially
      sectioned human embryos of developmental stages 13-19 (postovulatory days 32-46).
      At stage 13 the trabeculation of both ventricles was advanced and the muscular
      part of the interventricular septum well marked. Dorsal and ventral endocardial
      cushions were fused and the atrioventricular canal was divided into two parts. In
      embryos at stage 18 the membranous interventricular septum was developing and the
      interventricular foramen was obliterated. At stage 19 the membranous part of the
      interventricular septum was becoming more cellular in structure.

PMID- 18335409
TI  - Morphometric alterations of the rat spleen following formaldehyde exposure.
AB  - Formaldehyde is commonly used in the production of various industrial and medical
      products. At room temperature formaldehyde easily evaporates. Exposure to
      formaldehyde can be hazardous to human health. Studies show that the vapour can
      be the cause of clinical symptoms such as throat, eye, skin and nasal irritation.
      It can also decrease the production of IgM in the spleen cells. This study was
      designed to determine the morphometric changes to the spleen in rats when samples
      were exposed to formaldehyde for 18 weeks. A total of 28 albino Wistar rats aged
      6-7 postnatal weeks were divided into the following three case groups according
      to their exposure to formaldehyde: E1 (2 h/day, 2 days/week), E2 (2 h/day, 4
      days/week), E3 (4 h/day, 4 days/week) and one control group. When the exposure
      period had expired the animals were anaesthetised with chloroform. After cervical
      dislocation, the abdomen was dissected and spleen specimens were taken. These
      were sectioned and stained with the haematoxylin and eosin technique for
      morphometric study. Data was obtained from an Olympus light microscope and then
      analysed with SPSS (version 11.5) and one-way ANOVA test. The white pulp area and
      diameter and the marginal zone diameter were greater in group E3 than those in
      the other groups. The germinal centre area and diameter and the diameter of the
      periarterial lymphoid sheaths (PALS) were greater in group E2 than in other
      groups, although there was no significant difference between groups in the area
      of white pulp and the PALS diameter (p<0.05). This study showed that formaldehyde
      vapour can cause morphometric changes in the white pulp of the spleen in rats.

PMID- 18335410
TI  - Immunoexpression of constitutive and inducible cyclo-oxygenase isoforms in the
      rat foetal and maternal digestive tract.
AB  - Cyclo-oxygenase (COX), which catalyses the conversion of arachidonic acid to
      prostaglandin endoperoxide and prostanoids, is widely expressed in mammalian
      organs. The aim of the study was to evaluate the immunoexpression of the
      constitutive and inducible cyclo-oxygenase isoforms (COX-1 and COX-2
      respectively) in the oesophagus, stomach and the small and large bowels of
      untreated rat dams and foetuses on gestational day 21. The localisation of the
      COX isoforms was similar in the maternal and foetal organs, although the
      intensity of the reaction for COX-2 was stronger in the foetuses. Cytoplasmic COX
      1 immunostaining was found in myocytes of the muscularis propria, muscularis
      mucosae and the blood vessels. It was also positive in the endothelial cells,
      scattered stromal cells of the lamina propria and the ganglion cells of the nerve
      plexus in the bowels. Apart from the keratinised layer, a strong reaction was
      revealed in the stratified squamous epithelium of the oesophagus and forestomach.
      Negative or weakly positive staining was found in the mucus-secreting cells
      covering the surface, gastric pits and pyloric glands, as well as in the parietal
      cells and the chief cells. Weakly positive COX-1 immunostaining was observed in
      epithelial cells of the small intestine crypts, but in some cases enterocytes and
      goblet cells covering villi were also positive. In the colonic mucosa weak COX-1
      staining was typical of the absorptive, and goblet cells. The COX-2
      immunostaining was nuclear and/or cytoplasmic. An inconsistent positive reaction
      was seen in the muscle of the muscularis mucosae, muscularis propria and the
      blood vessels. Positive staining was also found in scattered stromal cells of the
      lamina propria and adventitia and the ganglion cells. Weak nuclear staining was
      found in the stratified squamous epithelium of the oesophagus and forestomach.
      Unlike the strong foetal reactivity in the epithelial cells of the glandular
      stomach, a negative or weakly positive reaction was seen in the maternal parietal
      and/or mucous-secreting surface stomach cells. Some epithelial cells of the
      crypts both in the small and large bowel were also COX-2 positive. In conclusion,
      constitutive and inducible COX isoforms were detected in the digestive tract of
      pregnant female and in foetuses. COX-1 was the predominant isoform in both the
      adult and foetal organs.

PMID- 18335411
TI  - Local differences in the position of the mental foramen.
AB  - The mental foramen has been reported to vary in position in different ethnic
      groups. Repeated failures during injections and operative procedures involving
      the mental foramen suggest the presence of local differences in a given
      population. The aim of the present study was to investigate possible local
      differences of the mental foramen in Eastern Anatolian individuals in the Turkish
      population. The present investigation is based on the examination of 70 adult
      mandibles. The study consisted of three measurements, to include the relations of
      the mental foramen to the following: 1) the lower teeth; 2) the body of mandible;
      3) the mandibular symphysis and posterior border of the ramus of the mandible.
      The most common position of the foramen was in line with the longitudinal axis of
      the second premolar tooth (relation IV), at the midpoint of the mandibular body
      height and at 1/3.5 of the distance from the mandibular symphysis to the
      posterior border of the ramus. Local differences of the mental foramen may occur
      in a population. Prior to surgery knowledge of the most common location of the
      foramen peculiar to a local population may enable effective mental block
      anaesthesia to be provided.

PMID- 18335412
TI  - Assessment of body mass index and hand anthropometric measurements as independent
      risk factors for carpal tunnel syndrome.
AB  - The goal of this study was to clarify the role of body mass index (BMI) (weight
      divided by square of height; kg/m2) and hand anthropometric measurements as
      independent risk determinants in the development of carpal tunnel syndrome (CTS)
      and their relationship to the severity of CTS. A total of 131 patients with
      clinical symptoms of CTS and 131 normal subjects were enrolled, of whom 121 were
      female both in the CTS cases and the controls. All cases were
      electrodiagnostically confirmed and assigned to three severity groups. BMI, wrist
      ratio, shape index, digit index and hand length/height ratio were measured in all
      participants. Mean values for each item were compared between cases and controls
      and severity subgroups. A logistic regression analysis was performed to determine
      independent CTS risk factors. The mean values of BMI, wrist ratio and shape index
      were significantly higher in all CTS patients and females compared to controls,
      whereas in males only BMI and wrist ratio were higher. The patients in the mild
      severity subgroup had a significantly lower age and wrist ratio. BMI, wrist ratio
      and shape index were found to be independent risk factors of CTS development in
      all patients and females. Our study showed BMI, wrist ratio and shape index as
      independent risk factors for CTS. These findings are of potential anatomical and
      clinical importance and outline the risk factors of anatomical malfunction of the
      wrist in CTS.

PMID- 18335413
TI  - Distribution of macrophages in the human fallopian tubes: an immunohistochemical
      and electron microscopic study.
AB  - The fallopian tubes are essential for the normal transport of gametes,
      fertilisation and early embryonic development and transport. Their locomotive
      force is mainly due to the contractility of the smooth muscle cells, as well as
      to the ciliary activity of the tubal epithelium. Steroid hormones such as
      oestradiol and progesterone mediate changes in tubal morphology, in particular
      the tubal epithelium. It is well known that macrophages participate in the immune
      system, but recent studies have shown that they also play other roles under
      physiological conditions. They are known to be a source of prostaglandins of the
      E series, which influence the contractility of the uterine tube. Lymphocytes in
      the tubal mucosa can be involved in the process of immune tolerance, which could
      enable sperms and blastocysts to be transported through the oviduct under normal
      conditions without the activation of local immune mechanisms. Most of the
      evidence for mucosal immune responses in the female reproductive tract is related
      to the vagina, with less information available for the uterus. The less known
      segment in this regard is the oviduct, which prompted us to review and summarise
      the current state of knowledge of the immune system at the level of the human
      oviduct. The present study was therefore undertaken to examine the distribution
      and morphological properties of macrophages in the endosalpingeal stroma and
      smooth muscle layer of the human fallopian tubes. Thirty fresh fallopian tubes
      were examined, taken at the proliferative (7 cases) and secretory (12 cases)
      phases of the menstrual cycle, and during the postmenopausal period (11 cases).
      Sections were stained by immunocytochemistry with a primary antibody (CD 68) and
      were used for counting the macrophages. Ultrathin sections were stained with lead
      citrate and uranyl acetate and studied by means of electron microscopy to asses
      the ultrastructure of the macrophages. A significant difference was observed
      between reproductive and postmenopausal women in the number of macrophages
      (p<0.05). This study may help to clarify the possible role of macrophages of the
      uterine tubes in some cases of infertility in females.

PMID- 18335414
TI  - Morphometric features of the right atrioventricular orifice in adult human
      hearts.
AB  - The normal data of the tricuspid valve complex is of great clinical importance in
      the light of progress in cardiosurgery and the development of novel operating
      techniques. A range of measurements for the right atrioventricular orifice in 96
      human adult hearts was examined by means of anatomical dissection, inspection,
      examination, and statistical analyses. The length of the attachment of the
      anterior leaflet increased significantly between group I (aged 18-40 years) and
      group II (aged 41-64 years) in women only. In men there were no significant
      differences in this parameter between any of the three age groups. In addition,
      the attachment length of the posterior leaflet in women increased statistically
      in the second age group. In men, in contrast, the attachment length of the
      posterior leaflet did not increase significantly between the first and second age
      groups and became significantly larger only in oldest age group, consisting of
      men aged over 65. No statistically significant differences between the three age
      groups were found for the attachment length of the septal leaflet (p>0.05). In
      female hearts significant increases in the frontal and sagittal dimensions of the
      tricuspid valve orifice were observed between the second age group and the group
      aged over 65. In male hearts both the frontal and sagittal dimensions increased
      significantly with advanced age. The right atrioventricular orifice expressed as
      the ellipse area was statistically greater than the triangular area (p<0.01) in
      each age group. It should be noticed that both areas increased significantly
      during ageing. This study has demonstrated that the shape of the right
      atrioventricular orifice evolves during life, from a triangular shape to a more
      elliptical shape.

PMID- 18335415
TI  - The subscapular artery and the thoracodorsal branch: an anatomical study.
AB  - The motive for this research was the use of the muscles of the scapular region in
      transposition, transplantation and reparative surgery and the need for more
      detailed knowledge of the blood supply to these muscles. In addition, the
      subscapular arterial tree may be used as a source of microvascular grafts to
      replace damaged or diseased portions of arteries, particularly in the hand and
      forearm. The research was conducted on 60 sides of corpses of adults of both
      sexes. It was noticed that the subscapular artery was present in 96.7% of cases
      and originated laterally to the pectoralis minor muscle in 76.7% of cases. The
      average calibre was 5.0 mm, and in 73.2% of cases it measured between 4.0 and 5.9
      mm. The average length was 18.0 mm, ranging from 10.0 to 29.9 mm (76.7%). It
      presented in its course important relations with the axillary nerve (69%) and
      with the radial nerve (82.8%). Its branches were collateral (subscapular muscle -
      61.3%) and terminal (except for the circumflex scapular artery), leading to the
      following muscles: serratus anterior (43.9%), latissimus dorsi (27.6%), and
      subscapular (23.3%). The thoracodorsal artery, one of the terminal branches, most
      frequently showed a calibre of between 2.0 and 3.9 mm (70.3%), collateral
      branches in 85.0%, was mainly distributed to the subscapular muscle (36.7%) and
      to the serratus anterior muscle (29.0%) and had terminal branches to the
      following muscles: latissimus dorsi (44.1%), serratus anterior (40.5%) and the
      subscapular (12.5%). The serratus anterior muscle received one branch in 39.5%
      and two branches in 41.9%, while the latissimus dorsi muscle received one branch
      in 66.7% and two branches in 23.1%.

PMID- 18335416
TI  - The prevalence of accessory heads of the flexor pollicis longus and the flexor
      digitorum profundus muscles in Egyptians and their relations to median and
      anterior interosseous nerves.
AB  - Entrapment neuropathy in the forearm is not uncommon. Surgical interference for
      nerve decompression should be preceded by accurate diagnosis of the exact cause
      and site of the nerve entrapment. The aim of the present study was to investigate
      the prevalence of accessory heads of the flexor pollicis longus and flexor
      digitorum profundus muscles (FPLah) and (FDPah) in Egyptians and their
      topographical relationship with both the median nerve and its anterior
      interosseous branch. A total of 42 upper limbs of embalmed cadavers, 36 from
      males and 6 from females, were examined to elucidate the prevalence of both the
      FPLah and the FDPah muscles, their origin, insertion, nerve supply and
      morphology. The distribution of these two muscles in the right and left male and
      female upper limbs and their relationship to the anterior interosseous and median
      nerves were recorded. The total lengths of both accessory muscles and the lengths
      of their fleshy bellies and tendons were also measured. The FPLah was found to be
      present more frequently (61.9%) than it was absent, whereas the FDPah was
      observed in only 14.24% of the specimens examined. The combination of the
      accessory muscles in the same forearm was noticed in 9.52% of cases. As regards
      side, the FPLah appeared in 77.7% of the right forearms and in 50% of the left,
      while the FDPah was found in only 25% of the left forearms. The accessory muscles
      showed no single morphology, as the FPLah appeared fusiform in 53.8%, slender in
      30.8% and voluminous fusiform in 15.4%, while the FDPah was slender in 66.6% and
      triangular in 33.3% of specimens. The FPLah arose mainly from the under surface
      of flexor digitorum superficialis, while the FDPah took its origin from the under
      surface of flexor digitorum superficialis or from the medial epicondyle. The
      insertion of the FPLah was mainly into the upper third of the FPL tendon, while
      the FDPah tendon joined the tendons of the flexor digitorum profundus muscle to
      the index or middle and ring fingers. The FPLah was found between the median
      nerve anteriorly and the anterior interosseous nerve posteriorly. Both FPLah and
      FDPah took their nerve supply mainly from the anterior interosseous nerve and,
      less frequently, from the median nerve. The mean values of the total lengths of
      FPLah and FDPah were 74.66 mm and 208.33 mm, respectively. Cadaveric dissection
      in this study confirmed the prevalence of the FPLah and FDPah in Egyptians and
      demonstrated the relationship of the FPLah to the median nerve and its anterior
      interosseous branch. These findings may provide the surgeon with information for
      the differential diagnosis of the causes and sites of anterior interosseous nerve
      syndrome and entrapment neuropathy of the median nerve in the forearm

PMID- 18335417
TI  - The clinical anatomy of the cephalic vein in the deltopectoral triangle.
AB  - Identification and recognition of the cephalic vein in the deltopectoral triangle
      is of critical importance when considering emergency catheterization procedures.
      The aim of our study was to conduct a cadaveric study to access data regarding
      the topography and the distribution patterns of the cephalic vein as it relates
      to the deltopectoral triangle. One hundred formalin fixed cadavers were examined.
      The cephalic vein was found in 95% (190 right and left) specimens, while in the
      remaining 5% (10) the cephalic vein was absent. In 80% (152) of cases the
      cephalic vein was found emerging superficially in the lateral portion of the
      deltopectoral triangle. In 30% (52) of these 152 cases the cephalic vein received
      one tributary within the deltopectoral triangle, while in 70% (100) of the
      specimens it received two. In the remaining 20% (38) of cases the cephalic vein
      was located deep to the deltopectoral fascia and fat and did not emerge through
      the deltopectoral triangle but was identified medially to the coracobrachialis
      and inferior to the medial border of the deltoid. In addition, in 4 (0.2%) of the
      specimens the cephalic vein, after crossing the deltopectoral triangle, ascended
      anterior and superior to the clavicle to drain into the subclavian vein. In these
      specimens a collateral branch was observed to communicate between the cephalic
      and external jugular veins. In 65.2% (124) of the cases the cephalic vein
      traveled with the deltoid branch of the thoracoacromial trunk. The length of the
      cephalic vein within the deltopectoral triangle ranged from 3.5 cm to 8.2 cm with
      a mean of 4.8+/-0.7 cm. The morphometric analysis revealed a mean cephalic vein
      diameter of 0.8+/-0.1 cm with a range of 0.1 cm to 1.2 cm. The cephalic vein is
      relatively large and constant, usually allowing for easy cannulation.

PMID- 18335418
TI  - Screening for thoracoabdominal aortic aneurysms in patients with aortoiliac
      atherosclerosis: a preliminary study.
AB  - Thoracoabdominal aortic aneurysms (TAAs) usually present with rupture and carry a
      high morbidity and mortality rate. Early detection of TAAs with screening methods
      and elective surgical repair could potentially diminish these complications. The
      present study was aimed at screening for TAA in patients with angiography-proven
      aortoiliac atherosclerosis (n=43). A group of patients without aortoiliac
      atherosclerosis was used as controls (n=15). Age, sex and aortic diameter at the
      level of the T12 vertebra were recorded. The subjects were divided into two age
      categories, the first made up of those aged less than 65 years and the second
      those aged 65 years or more. A T12 aortic diameter greater than 35 mm was used to
      indicate TAA. Statistical analyses were performed by independent t-test and
      general linear model with age category, sex and atherosclerosis as factors. The
      mean T12 aortic diameters were greater in patients with atherosclerosis than in
      the control group (25.2+/-5.0 vs. 22.9+/-2.4 mm; p=0.034). Two out of 43 patients
      (4.7%) with aortoiliac atherosclerosis had TAA, while no one in the control group
      had TAA. A general linear model showed that the interaction of age category and
      sex significantly affected the T12 aortic diameter [F (1.49)=4.044, p=0.050].
      Post hoc (LSD) tests revealed that male patients aged over 65 had greater T12
      aortic diameters than other patients. We conclude that patients with aortoiliac
      atherosclerosis may be at greater risk for developing TAA. Ageing and male sex
      may also be associated with thoracoabdominal aortic enlargement.

PMID- 18335422
TI  - Generalized nonaqueous sol-gel synthesis of different transition-metal niobate
      nanocrystals and analysis of the growth mechanism.
AB  - A general nonaqueous route for the synthesis of phase-pure transition-metal
      niobate (InNbO(4), MnNb(2)O(6), and YNbO(4)) nanocrystals was developed based on
      the one-pot solvothermal reaction of niobium chloride and the corresponding
      transition-metal acetylacetonates in benzyl alcohol at 200 degrees C. All samples
      were carefully characterized by XRD, TEM, HRTEM, and energy-dispersive X-ray
      (EDX) analysis. The crystallization mechanism of these niobate nanocrystals
      points to a two-step pathway. First, metal hydroxide crystals and amorphous
      niobium oxide are formed. Second, metal niobate nanocrystals are generated from
      the intermediates by a dissolution-recrystallization mechanism. The reaction
      mechanisms, that is, the processes responsible for the oxygen supply for oxide
      formation, were found to be rather complex and involve niobium-mediated ether
      elimination as the main pathway, accompanied by solvolysis of the acetylacetonate
      ligands and benzylation reactions.

PMID- 18335423
TI  - Conformational constraint in protein ligand design and the inconsistency of
      binding entropy.
AB  - It is an accepted practice in ligand design to introduce conformational
      constraint with the expectation of improving affinity, justified by the
      theoretical possibility that an unfavorable change in binding entropy will be
      reduced. This rationale of minimizing the entropic penalty through imposing
      structural constraints upon a ligand, however, has been voiced more often than
      verified. Here we examine three modified cyclic peptides, along with multiple
      versions of their linear control analogs, and determine their thermodynamic
      parameters when binding the same host, the third PDZ domain (PDZ3) of the
      mammalian postsynaptic density-95 (PSD-95) protein. To begin a two-stage
      investigation, the initial evaluation involved solution binding studies with
      isothermal titration calorimetry (ITC), which provided the changes in Gibbs free
      energy (DeltaG), enthalpy (DeltaH), and entropy (TDeltaS) upon formation of the
      protein-ligand complex. In the second stage, a selected macrocycle along with two
      matched linear controls were subjected to more rigorous analysis by ITC, which
      included (1) change in heat of buffer ionization (DeltaH(ion)) titrations, to
      examine the role of proton transfer events; (2) change in heat capacity
      (DeltaC(p)) determinations, to indirectly probe the nature of the binding
      surface; and (3) osmotic stress experiments, to evaluate desolvation effects and
      quantitate water release. Together, these demonstrate that the entropic
      relationship between a macrocyclic ligand and a linear counterpart can be a
      complex one that is difficult to rationalize. Further, the addition of constraint
      can, counterintuitively, lead to a less favorable change in binding entropy. This
      underscores the need to use matched linear control ligands to assure that
      comparisons are made in a meaningful manner.

PMID- 18335424
TI  - Structural insights into the elastin mimetic (LGGVG)6 using solid-state 13C NMR
      experiments and statistical analysis of the PDB.
AB  - Elastin is a crosslinked hydrophobic protein found in abundance in vertebrate
      tissue and is the source of elasticity in connective tissues and blood vessels.
      The repeating polypeptide sequences found in the hydrophobic domains of elastin
      have been the focus of many studies that attempt to understand the function of
      the native protein on a molecular scale. In this study, the central residues of
      the (LGGVG)(6) elastin mimetic are targeted. Using a combination of a statistical
      analysis based on structures in the Brookhaven Protein Data Bank (PDB), 1D cross
      polarization magic-angle-spinning (CPMAS) NMR spectroscopy, and 2D off-magic
      angle-spinning (OMAS) spin-diffusion experiments, it is determined that none of
      the residues are found in a singular regular, highly ordered structure. Instead,
      like the poly(VPGVG) elastin mimetics, there are multiple conformations and
      significant disorder. Furthermore, the conformational ensembles are not
      reflective of proteins generally, as in the PDB, suggesting that the structure
      distributions in elastin mimetics are unique to these peptides and are a salient
      feature of the functional model of the native protein.

PMID- 18335425
TI  - Delivery of peptides to the brain: emphasis on therapeutic development.
AB  - Peptides and regulatory proteins hold great promise as therapeutic agents for the
      central nervous system (CNS). However, the blood-brain barrier (BBB) is a major
      obstacle to the delivery of these potential therapeutics to their site of action.
      We concentrate here on the vascular BBB, which is comprised of the capillary bed
      of the brain specially modified to prevent the production of a plasma
      ultrafiltrate. For many peptides and proteins, this physical barrier is
      reinforced by enzymatic activities at the BBB, CNS, and peripheral tissues, short
      half-lives and large volumes of distribution in the blood, binding proteins in
      blood, and brain-to-blood efflux systems. Nevertheless, there are pathways
      through which substances can cross. Small, lipid soluble substances cross by the
      nonsaturable mechanism of transmembrane diffusion, but even water-soluble
      peptides can cross to some degree. Many endogenous peptides and regulatory
      proteins cross the BBB by way of selective, saturable transport systems. For
      enzymatically resistant substances with long circulating half-lives and small
      volumes of distribution, such as antibodies, erythropoietin, and enzymes,
      substances can enter the CNS in therapeutic amounts through the residual leak of
      the BBB, termed the extracellular pathways. Recent examples show that the BBB
      transporters for peptides and regulatory substances are modifiable. This provides
      both a therapeutic opportunity and the potential for disease to arise from BBB
      dysfunctions. In the last case, the BBB itself is a therapeutic target.

PMID- 18335426
TI  - Crystal structures of peptide enantiomers and racemates: probing conformational
      diversity in heterochiral Pro-Pro sequences.
AB  - Multiple conformational states in heterochiral diproline sequences have been
      characterized in the solid state by the determination of the crystal structures
      of seven tripeptides in enantiomeric and racemic forms. The sequences of the type
      Piv-DPro-LPro-DXxx-NHMe (D-L-D) [DXxx=DVal 1, DLeu 3, and DPhe 5] and their
      corresponding enatiomeric L-D-L sequences [LXxx=LVal 2, LLeu 4, and LPhe 6] have
      been investigated. Single crystals have been obtained for the pure enantiomers 1,
      2, 3, 4 and for the racemates 1/2, 3/4, and 5/6. For Xxx=Leu, mirror image
      conformations (type II/II' beta-turns) at Pro-Leu segment are obtained. For
      Xxx=Val, a LPro-DPro type II beta-turn in 2 and an open/extended structure is
      obtained in the solvated form of the enantiomer 1. For Xxx=Phe, suitable crystals
      could not be obtained for enatiomeric peptides. The racemate 5/6 revealed a cis
      peptide bond between the diproline segment with the absence of any intramolecular
      hydrogen bonds. Crystal structures of enantiomers and racemates prove useful in
      characterizing the multiple conformational states that are accessible to Pro-Pro
      segments.

PMID- 18335427
TI  - B12-retro-riboswitches: guanosyl-induced constitutional switching of B12
      coenzymes.
AB  - Complete B12 derivatives are natural "molecular switches" as a result of the
      coordinative switch ("base on" or "base off") of the natural nucleotide base.
      Certain predesigned B12-nucleotide conjugates were shown recently to behave as
      "retro riboswitches", in which the nucleotide environment modified the
      equilibrium between these two isomeric B12 structures. In contrast, the "reverse"
      situation has been discovered in natural B12 riboswitches, in which the binding
      of coenzyme B12 induces a conformational switch in the RNA species. The first
      (predesigned) B12-retro-riboswitches were DNA conjugates of methylcobalamin. We
      describe herein two representative B12-retro-riboswitches, in which an appended
      (RNA) nucleotide is used to destabilize the base-on form and induce the base-on
      to base-off switch. Through use of heterogeneous solid-phase synthetic methods,
      Co(beta)-cyanocobalamin-(3''-->2')-2''-methoxyguaninyl-3''-ate was prepared first
      as the crucial covalent RNA conjugate of vitamin B12. This cyanocorrinoid opened
      the door to two organometallic B12-nucleotide conjugates, which were made by
      electrosynthetic means: the cyanocorrinoid was cleanly methylated or adenosylated
      at the cobalt center to furnish covalent RNA conjugates of the organometallic B12
      cofactors methylcobalamin and coenzyme B12, respectively. At room temperature,
      aqueous solutions of both of these organometallic RNA-B12 conjugates exhibited
      properties indicative of significant weakening of the axial (Co--N) bond (of
      their base-on forms) and of an enhanced formation of the base-off species. The
      base-on to base-off switch was studied by UV/Vis and NMR spectroscopic studies,
      which showed that the switch was very temperature-dependent and was accentuated
      with increasing temperatures. Thermodynamic data of the two organometallic RNA
      B12 conjugates revealed an important contribution of entropic effects to the
      observed base-on to base-off switch. The two organometallic RNA-B12 conjugates
      thus acted as B12-retro-riboswitches and allowed the observation of a temperature
      dependent reverse switch in the B12 cofactor moiety, induced by the appended
      nucleotide moiety. This behavior may be of interest in the "RNA-world"
      hypothesis, in which (simple) B12 derivatives are thought to act as possible
      catalytic enhancers ("cofactors") in RNA-based "B12 ribozymes".

PMID- 18335428
TI  - Engineering nanorafts of calixarene polyphosphonates.
AB  - The water-soluble calix[4]arene bearing p-substituted phosphonic acid groups is
      accessible in five steps in overall 62 % yield, with the hydrogen-bonding prowess
      of the acidic groups dominating its self-assembly processes. These include the
      formation of 3.0(3) nm and 20(2) nm nanorafts of the calixarene in water using
      spinning disc processing, stabilized by acetonitrile, and nanorafts in the gas
      phase (<or=20 molecules). The 20(2) nm particles transform into 3.0(3) nm
      particles prior to crystallization into a compact bilayer, whereas
      crystallization in the presence of large organic molecules gives an expanded
      bilayer interposed by layers of water molecules.

PMID- 18335429
TI  - Tin-oxo clusters based on aryl arsonate anions.
AB  - Reactions of Ph(3)SnOH or Ph3SnCl with aryl arsonic acids RAsO3H2, where R=C6H5
      (1), 2-NH2C6H4 (2), 4-NH2C6H4 (3), 2-NO2C6H4 (4), 3-NO2C6H4 (5), 4-NO2C6H4 (6), 3
      NO2-4-OHC6H3 (7), 2-ClC6H4 (8) and 2,4-Cl2C6H3 (9), gave 18 Sn-O cluster
      compounds. These compounds can be classified into four types: type A:
      [{(PhSn)3(RAsO3)3(mu3-O)(OH)(R'O)2}2Sn] (R=C6H5, 2-NH2C6H4, 4-NH2C6H4, 2-NO2C6H4,
      3-NO2C6H4, 2-ClC6H4, 2,4-Cl2C6H3, and 3-NO2-4-OHC6H3; R'=Me or Et); type B:
      [{(PhSn)3(RAsO3)(2)(RAsO3H)(mu3-O)(R'O)2}2] (R=4-NO2C6H4, R'=Me); type C:
      [{(PhSn)3(RAsO3)3(mu3-O)(R'O)3}2Sn] (R=2,4-Cl2C6H3, R'=Me); type D: [{Sn3Cl3(mu3
      O)(R'O)3}(2)(RAsO3)4] (R=2-NO2C6H4 and 4-NO2-C6H4; R'=Me or Et). Structures of
      types A and B contain [Sn3(mu3-O)(mu2-OR')2] building blocks, while in types C
      and D the stannoxane cores are built from two [Sn3(mu3-O)(mu2-OR')3] building
      blocks. The reactions proceeded with partial or complete dearylation of the
      triphenyltin precursor. These various structural forms are realized by subtle
      changes in the nature of the organotin precursors and aryl arsonic acids. The
      syntheses, structures, and structural interrelationship of these
      organostannoxanes are discussed.

PMID- 18335430
TI  - Nonpolar dihydrogen bonds--on a gliding scale from weak dihydrogen interaction to
      covalent H-H in symmetric radical cations [HnE-H-H-EHn]+.
AB  - The electronic structures and bonding patterns for a new class of radical
      cations, [HnE-H-H-EHn]+ (EHn=element hydride, E=element of Groups 15-18), have
      been investigated by applying quantum-chemical methods. All structures
      investigated give rise to symmetric potential energy minimum structures. We
      envisage clear periodic trends. The H--H bond length is shorter for elements
      toward the bottom of the periodic table of elements, and a short H--H bond
      corresponds to accumulation of electron density in the central H--H region. All
      [HnE-H-H-EHn]+ of Groups 15-17 are thermodynamically unstable towards loss of
      either H2 or H. The barriers for these dissociations are rather low. The Group 18
      congeners, except E=Xe, appear to be global minima of the respective potential
      energy surfaces. The findings are discussed in terms of H2 bond activation, and a
      general mechanistic scheme for the standard reduction process 2H+ + 2e(-) --> H2
      is given. Finally, it is proposed that some of the symmetric radical cations are
      likely to be observed in mass spectrometric or matrix isolation experiments.

PMID- 18335431
TI  - The effect of the environment on the mechanical properties of medical grade
      silicones.
AB  - Silicone spacers have been in use as replacement joints in the human hand for
      over 30 years. Since they were first used there has been a number of designs all
      of which have had problems with fracture. This may be due to a defect in the
      material caused during implantation, or by bony intrusions within the arthritic
      hand after implantation. The aim of this research was to investigate the effect
      of the environment on the mechanical properties of medical grade silicones used
      for human implantation. The materials were subjected to static tensile testing
      after various forms of ageing. The environmental conditions included temperatures
      of 37 and 80 degrees C and the environments of Ringer's solution, distilled
      water, and air. The environmental conditions employed resulted in reduced
      mechanical strength with ageing time of the silicones. This research supports the
      view that failure of silicone implants in the hand could be partly attributed to
      the effects of environmental ageing of the material.

PMID- 18335432
TI  - Nanophase separation of polymers exposed to simulated bonding conditions.
AB  - Under in vivo conditions, there is little control over the amount of water left
      on the tooth during dentin bonding. As a result, it is possible to leave the
      dentin surface so wet that the adhesive actually undergoes physical separation
      into hydrophobic- and hydrophilic-rich phases. Using tapping mode atomic force
      microscopy/PhaseImaging technique, nanosized phases with worm-like features were
      found on the surface of model HEMA/BisGMA dentin adhesives cured in the presence
      of varying concentrations of water. The phase contrast became evident with the
      increase of water concentration in the initial adhesive formulation and varied
      with the ratio of hydrophilic/hydrophobic composition. Oversaturated water
      droplets of variable sizes may accumulate as micro-voids within the hydrophilic
      and hydrophobic polymer phases. The phase domains were also identified following
      ethanol-etching in combination with SEM/AFM techniques.

PMID- 18335433
TI  - Antimicrobial activity and local release characteristics of chlorhexidine
      diacetate loaded within the dental copolymer matrix, ethylene vinyl acetate.
AB  - In vitro results are presented for a novel oral drug-delivery system ultimately
      intended for treatment of oral infections in immunocompromised patients. Test
      samples of ethylene vinyl acetate copolymer (EVA) containing chlorhexidine
      diacetate (CDA) showed desirable antimicrobial properties and steady, slow
      release into aqueous and other media after an initial burst of drug release in
      the first day of liquid exposure. By washing away this initial burst, the
      proposed mouthguard device should be capable of sustained delivery of locally
      effective CDA concentrations far below systemically toxic levels. A prolonged
      room temperature shelf-life of at least 1 year, and effectivity against a wide
      range of oral bacteria and Candida species was demonstrated. Drug loaded films
      showed a top-to-bottom asymmetry in drug release, but good lateral homogeneity,
      and a linear relationship between initial CDA loading concentration (from 0.63 to
      10 wt %) and days 3-14 release rates in a static aqueous environment. The EVA
      matrix containing CDA appears to possess many suitable properties for localized
      oral delivery of sustained antimicrobial activity.

PMID- 18335434
TI  - Effect of porosity and pore size on microstructures and mechanical properties of
      poly-epsilon-caprolactone- hydroxyapatite composites.
AB  - The influence of variant pore-size and porosity on the microstructure and the
      mechanical properties of poly-epsilon-caprolactone (PCL) and hydroxyapatite (HA)
      composite were examined for an optimal scaffold in bone tissue engineering. Three
      various amounts of sodium chloride (NaCl, as porogens) with two distinct particle
      size ranges (212-355 mum and 355-600 mum) were blended into PCL and HA mixture,
      followed by a leaching technique to generate PCL-HA scaffolds with various pores
      and porosity. The porosities of the scaffolds were correlated with the porogen
      size and concentration. The morphological properties of the resulting scaffolds
      were assessed by micro-computerized tomography (muCT), scanning electron
      microscopy (SEM), and energy dispersive X-ray analysis (EDX). Extensive PCL-HA
      pore interconnections with thinner pore walls were present in scaffolds with
      higher concentration (4:1 w/w) and larger particulate of porogen used in the
      fabrication process. Embedding of HA particles in the scaffold resulted in rough
      surfaces on the composites. Instron actuator testing indicated that the tensile
      strengths and Young's moduli of scaffolds were influenced by both the porosities
      and pore sizes of the scaffold. It was apparent that increasing the concentration
      of porogen compromised the mechanical properties; and a larger porogen particle
      size led to increased tensile strength but a reduction in Young's modulus.
      Overall, the data indicated that modification of the concentration and particle
      size of porogen altered the porous features and mechanical strength of HA-PCL
      scaffolds. This provided means to manipulate the properties of biocompatible cell
      supporting scaffolds for use as bone graft substitutes.

PMID- 18335435
TI  - The role of hydroxyapatite as solid signal on performance of PCL porous scaffolds
      for bone tissue regeneration.
AB  - Highly porous composites made up of biodegradable poly-epsilon-caprolactone (PCL)
      and stoichiometric hydroxyapatite (HA) particles have been developed as substrate
      for bone-tissue regeneration. The processing technique consists of phase
      inversion and particulate (salt crystals) leaching. Three different HA contents
      (13, 20 and 26 vol %) in PCL-based composite were considered in this study. Pore
      microstructure with fully interconnected network and pore sizes ranging around a
      few hundred of mum (macroporosity) was obtained as a result of salt particles
      removal by leaching process. Several microns (microporosity) porosity was also
      created through phase inversion of polymer solution. Total porosity up to 95% was
      achieved. Human marrow stromal cells (MSC) were seeded onto porous PCL-based
      composites for 1-5 weeks and cultured in osteogenic medium. MSC were able to
      adhere and grow on PCL-based substrates with a plateau at 3-4 weeks. However, the
      small effect of bioactive signals on the biological response evaluated in MSC
      cell culture suggests a prior role of topography on the biological response.
      Importantly, the presence of HA as a bioactive solid signal determines an
      increase of mechanical properties. On the overall, the results indicated that
      porous PCL-based composites are potential candidate for bone substitution with
      beneficial influence on structural characteristics by solid signal addition.

PMID- 18335436
TI  - Selection of a practical assay for the determination of the entire range of
      acetyl content in chitin and chitosan: UV spectrophotometry with phosphoric acid
      as solvent.
AB  - The rapidly expanding use of chitomaterials in biomedical applications demands
      accurate and precise analytical methods to determine physico-chemical
      characteristics, especially the acetyl content of the sample. The analytical
      methods available for the determination of the acetyl content of the biomaterials
      are quite different in efficiency, accuracy and precision. Out of 22 analytical
      methods reviewed, XRD, DSC, FTIR (KBr pellet), solid state (13)C CP/MAS NMR, and
      acid hydrolysis-HPLC and the spectrophotometry assay using phosphoric acid as
      solvent (PUV) were selected in this study. The validity and applicability of
      these methods were investigated with a wide range of chitin and chitosan samples
      varying acetyl content, preparation methods, and sources. The XRD, DSC, and FTIR
      (KBr pellet) methods showed poor accuracy with the samples of diverse
      preparations and sources. The PUV method was modified and accuracy of the method
      was examined against absolute methods: solid state (13)C CP/MAS NMR and acid
      hydrolysis-HPLC methods. The correlations between these three methods were >0.9.
      Therefore, the PUV method was selected as the most generally acceptable method
      based on its accuracy, reliability, simplicity, and instrument availability.

PMID- 18335437
TI  - Fabrication and characteristic analysis of a poly(propylene fumarate) scaffold
      using micro-stereolithography technology.
AB  - Scaffold fabrication for regenerating functional human tissues has an important
      role in tissue engineering, and there has been much progress in research on
      scaffold fabrication. However, current methods are limited by the mechanical
      properties of existing biodegradable materials and the irregular structures that
      they produce. Recently, several promising biodegradable materials have been
      introduced, including poly(propylene fumarate) (PPF). The development of micro
      stereolithography allows the fabrication of free-form 3D microstructures as
      designed. Since this technology requires a low-viscosity resin to fabricate fine
      structures, we reduced the viscosity of PPF by adding diethyl fumarate. Using our
      system, the curing characteristics and material properties of the resin were
      analyzed experimentally. Then, we fabricated waffle shape and 3D scaffolds
      containing several hundred regular micro pores. This method controlled the pore
      size, porosity, interconnectivity, and pore distribution. The results show that
      micro-stereolithography has big advantages over conventional fabrication methods.
      In addition, the ultimate strength and elastic modulus of the fabricated
      scaffolds were measured, and cell adhesion to the fabricated scaffold was
      observed by growing seeded cells on it. These results showed that the PPF/DEF
      scaffold is a potential bone scaffold for tissue engineering.

PMID- 18335438
TI  - Facial augmentation with porous polyethylene (Medpor)--histological evidence of
      intense foreign body reaction.
AB  - In a previous study by our group evaluating the clinical use of Medpor implants
      as augmentation material in the facial skeleton, we examined cases with
      unexpected intense foreign body reaction and focal disintegration of the implant
      material. The present study evaluates the histological findings in the largest
      series of explanted Medpor samples from human beings so far. Altogether 10
      samples were harvested during revision surgery due to aesthetic contouring or due
      to infection. The average time from implantation to removal of the implants was
      8.1 months. Paraffin embedding was employed for improved histological analysis.
      Chronic inflammation and foreign body giant cell reaction were seen in all cases.
      Intracytoplasmatic phagocytosis of disintegrated pieces of Medpor was seen as
      well as focal destruction of the material. From the histological point of view it
      is no longer justified to regard Medpor as an immunologically inert material.
      Nevertheless the reaction does not seem to be severe enough to compromise the
      stability and volume of the implant from a clinical point of view.

PMID- 18335439
TI  - Evaluation of a flexible collagen surgical patch for reinforcement of a fascial
      defect: Experimental study in a sheep model.
AB  - There is a need for a surgical mesh that can be used in general surgical
      procedures for reinforcement or repair of soft tissue. Collagen based surgical
      meshes may possess the appropriate qualities. In this study, the potential of a
      collagen product BioBlanket Surgical Mesh to facilitate soft tissue repair in an
      ovine fascial defect model in vivo was evaluated. BioBlanket Surgical Mesh
      facilitated soft tissue repair in an ovine fascial defect model in vivo.
      Superficial fascial surgical sites were evaluated grossly, histologically, and
      mechanically at 6 and 12 week time points. BioBlanket Surgical Mesh and the
      predicate device Restore Orthobiologic Implant both performed favorably when
      implanted in superficial fascial defects compared with the negative control empty
      defect.

PMID- 18335440
TI  - An internet database for the classification and dissemination of information
      about hazardous chemicals and occupational diseases.
AB  - BACKGROUND: The amount of information about hazardous agents in the workplace
      exceeds the capacity of human memory. There is a need to accurately represent or
      map this scientific knowledge for digital storage and retrieval. METHODS: A
      relational database of hazardous chemicals and occupational diseases was
      constructed by first collecting and sifting through the large volume of
      information. The information was indexed with a controlled vocabulary and
      documented with references to the scientific literature. RESULTS: The evolving
      database is available on the website of the National Library of Medicine. It
      enables users to browse categories and query by pick lists. Users can drill down
      to find specific information that may be useful for intervention and prevention.
      CONCLUSIONS: The large amount of information needed to support decisions
      concerning occupational exposures and diseases can be distilled, classified, and
      summarized in a relational database and disseminated by means of the World Wide
      Web to assist in the prevention of work-related diseases.

PMID- 18335441
TI  - Iron chelates of 2,2'-bidipyrrin: stable analogues of the labile iron bilins.
AB  - A unique series of halogenidoiron(III) complexes of the open-chain tetrapyrrolic
      ligand 2,2'-bidipyrrin (bpd) ([FeX(bdp)] X=F, Cl, Br, I) was prepared from simple
      pyrrolic and bipyrrolic precursors and iron chloride by a one-pot
      condensation/metalation strategy, followed by salt metathesis with CsF, LiBr, or
      NaI. Crystallographic analysis revealed that in all cases the 2,2'-bidipyrrin
      ligand is forced to reside in a helical conformation when bound to the iron atom.
      Whereas the extremely sensitive fluorido derivative was isolated as a CsF adduct
      and forms 1D polymeric chains in the solid state, the more stable chlorido,
      bromido, and iodido derivatives crystallize as discrete monomeric molecules with
      a distorted pentacoordinate iron(III) ion in an intermediate spin ground state.
      Magnetic susceptibility measurements and Mossbauer data of the compounds are in
      agreement with this interpretation. In solution, however, all the compounds are
      pentacoordinate with the iron atom in the high-spin (S=5/2) state and dynamic
      with respect to helix inversion. In the presence of air, the iron chelates react
      stepwise with the nucleophiles methanol and imidazolate at the tetrapyrrole
      terminal alpha,omega-positions, presumably through the hexacoordinate species
      [Fe(bdp)(MeOH)2]+ and [Fe(im)2-(bdp)](-), respectively. The successive increase
      of strain at these positions results in increasingly labile intermediates that
      spontaneously release the iron ion from the mono- or disubstituted tetrapyrrole
      ligands.

PMID- 18335442
TI  - Three-dimensional mesoporous gallosilicate with Pm3n symmetry and its unusual
      catalytic performances.
AB  - Three-dimensional, mesoporous-cage-type, GaSBA-1 materials with different
      n(Si)/n(Ga) ratios have been successfully prepared for the first time by using a
      low hydrochloric acid to silicon (n(HCl)/n(Si)) molar ratio in the synthesis gel
      by templating with cetyltriethylammonium bromide as the structure-directing agent
      in a highly acidic medium. The obtained materials have been unambiguously
      characterized in detail by several sophisticated techniques including X-ray
      diffraction (XRD), N(2) adsorption, high-resolution transmission electron
      microscopy, high-resolution scanning electron microscopy, energy dispersive
      spectroscopy, elemental mapping, and (29)Si magic-angle-spinning NMR
      spectroscopy. XRD and nitrogen adsorption results reveal that the structures of
      the GaSBA-1 materials resemble that of SBA-1, which possesses a cubic, three
      dimensional, cage-type structure with open windows. In addition, the specific
      surface area and the specific pore volume of the GaSBA-1 materials are much
      higher than those of the SBA-1 silica, which are very important for the catalytic
      applications. The amount of Ga cation in the SBA-1 silica framework has been
      found to play a critical role in controlling the morphology and the pore diameter
      of the materials. Finally, the catalytic activity in the tert-butylation of
      phenol with tert-butanol as the alkylating agent has been investigated and the
      results are compared with those of other mesoporous catalysts such as AlMCM-41,
      FeMCM-41, FeAl-MCM-41, and FeSBA-1. Moreover, the effect of various reaction
      parameters such as the reaction temperature, reactant feed ratio, and time-on
      stream on the phenol conversion in the tert-butylation of phenol over GaSBA-1
      catalysts has been demonstrated. Among the catalysts examined, GaSBA-1(17), in
      which the number in the parenthesis denotes the n(Si)/n(Ga) ratio, showed
      remarkable activity with a high conversion of phenol and selectivity to 4-tert
      butylphenol; it was found to be superior over other mesoporous catalysts used in
      the study.

PMID- 18335443
TI  - Controllable synthesis of VSB-5 microspheres and microrods: growth mechanism and
      selective hydrogenation catalysis.
AB  - Nanoporous VSB-5 nickel phosphate molecular sieves with relatively well
      controllable sizes and morphology of microspheres assembled from nanorods were
      synthesized at 140 degrees C over a short time in the presence of
      hexamethylenetetramine (HMT) by a facile hydrothermal method. The pH value,
      reaction time, and ratio of HMT to NaHPO2.H2O crucially influence the morphology
      and quality of the final products. By adjusting the pH value of the initial
      reaction solution, the morphology changes from disperse rods to microspheres
      assembled from rods and finally to a large quantity of fibers, and the diameters
      of the VSB-5 rods can be varied. The catalytic activity of VSB-5 in selective
      hydrogenation of several unsaturated organic compounds was tested. Nickel(II) in
      VSB-5 can selectively catalyze hydrogenation of C=C in trans-cinnamaldehyde and 3
      methylcrotonaldehyde. In addition, since nitrobenzene (NB) and 2
      chloronitrobenzene could be reduced to aniline (AN) and 2-chloroaniline with high
      selectivity, VSB-5 could have potential applications in synthesizing dyes,
      agrochemicals, and pharmaceuticals.

PMID- 18335444
TI  - Photo gel-sol/sol-gel transition and its patterning of a supramolecular hydrogel
      as stimuli-responsive biomaterials.
AB  - In a focused library of glycolipid-based hydrogelators bearing fumaric amide as a
      trans-cis photoswitching module, several new photoresponsive supramolecular
      hydrogelators were discovered, the gel-sol/sol-gel transition of which was pseudo
      reversibly induced by light. Studying the optimal hydrogel by NMR spectroscopy
      and various microscopy techniques showed that the trans-cis photoisomerization of
      the double bond of the fumaric amide unit effectively caused assembly or
      disassembly of the self-assembled supramolecular fibers to yield the macroscopic
      hydrogel or the corresponding sol, respectively. The entanglement of the
      supramolecular fibers produced nanomeshes, the void space of which was roughly
      evaluated to be 250 nm based on confocal laser scanning microscopy observations
      of the size-dependent Brownian motion of nanobeads embedded in the supramolecular
      hydrogel. It was clearly shown that such nanomeshes become a physical obstacle
      that captures submicro- to micrometer-sized substrates such as beads or bacteria.
      By exploiting the photoresponsive property of the supramolecular nanomeshes, we
      succeeded in off/on switching of bacterial movement and rotary motion of bead
      tethered F(1)-ATPase, a biomolecular motor protein, in the supramolecular
      hydrogel. Furthermore, by using the photolithographic technique, gel-sol
      photopatterning was successfully conducted to produce sol spots within the gel
      matrix. The fabricated gel-sol pattern not only allowed regulation of bacterial
      motility in a limited area, but also off/on switching of F1-ATPase rotary motion
      at the single-molecule level. These results demonstrated that the photoresponsive
      supramolecular hydrogel and the resulting nanomeshes may provide unique
      biomaterials for the spatiotemporal manipulation of various biomolecules and live
      bacteria.

PMID- 18335445
TI  - Complexation of L-lactate with boronic acids: a solution and holographic
      analysis.
AB  - Boronic acids have been used as receptors for the detection of diols and alpha
      hydroxy acids. The incorporation of 3-acrylamide phenyl boronic acid (3-APB) into
      a hydrogel generates a suitably responsive and fully reversible holographic
      sensor for L-lactate. However, it was also found that the use of 3-APB resulted
      in the sensor being responsive towards a number of other compounds containing two
      hydroxy groups. This report details the further investigation into the reaction
      between L-lactate and three boronic acid-based receptors, both in the holograms
      and in solution, in order to establish the mechanism of binding. A novel boronate
      receptor is proposed based on this understanding.

PMID- 18335446
TI  - A new photothermal therapeutic agent: core-free nanostructured Au x Ag1-x
      dendrites.
AB  - A new class of Au(x)Ag(1-x) nanostructures with dendrite morphology and a hollow
      interior were synthesized by using a replacement reaction between Ag dendrites
      and an aqueous solution of HAuCl(4). The Ag nanostructured dendrites were
      generated by the reaction of AgNO(3) with ascorbic acid in a methanol/water
      system. The dendrites resemble a coral shape and are built up of many stems with
      an asymmetric arrangement. Each stem is approximately 400 nm in length and 65 nm
      in diameter. The bimetallic composition of Au(x)Ag(1-x) can be tuned by the
      addition of different amounts of HAuCl(4) to the Ag dendritic solution. The
      hollowing process resulted in tubular structures with a wall thickness of 10.5 nm
      in Au(0.3)Ag(0.7) dendrites. The UV/Vis spectra indicate that the strongest NIR
      absorption among the resulting hollow Au(x)Ag(1-x) dendrites was in
      Au(0.3)Ag(0.7). The MTT assay was conducted to evaluate the cytotoxicity of Ag
      dendrites, hollow Au(0.06)Ag(0.94) and Au(0.3)Ag(0.7) dendrites, and Au nanorods.
      It was found that hollow Au(0.06)Ag(0.94) and Au(0.3)Ag(0.7) dendrites exhibited
      good biocompatibility, while both Ag dendrites and Au nanorods showed dose
      dependent toxicity. Because of absorption in the NIR region, hollow
      Au(0.3)Ag(0.7) dendrites were used as photothermal absorbers for destroying A549
      lung cancer cells. Their photothermal performance was compared to that of Au
      nanorod photothermal therapeutic agents. As a result, the particle concentration
      and laser power required for efficient cancer cell damage were significantly
      reduced for hollow Au(0.3)Ag(0.7) dendrites relative to those used for Au
      nanorods. The hollow Au(0.3)Ag(0.7) nanostructured dendrites show potential in
      photothermolysis for killing cancer cells.

PMID- 18335447
TI  - Development of in situ electrochemical scanning electron microscopy with ionic
      liquids as electrolytes.
AB  - We report that ionic liquids (ILs) can be observed by electron microscopy without
      any charging of the liquid. Based on this, we present an in situ electrochemical
      scanning electron microscopy (in situ ECSEM) system. The key technology that
      enables in situ ECSEM is that charges can be removed from an IL by grounding it
      with a Pt wire, even if the IL is in an insulating glass cell. As a first
      demonstration, we describe the redox reaction of a polypyrrole (PPy) film
      accompanied by changes in its thickness when it is polarized by the film
      deposited Pt electrode in the IL. Furthermore, energy-dispersive X-ray
      fluorescence (EDX) analysis can be employed for the electrode polarized in the
      IL. The component analysis by EDX of PPy in an IL containing K+ as a marker,
      reveals doping of electrolyte cations into the PPy film upon the latter's
      reduction and dedoping of cations from the film upon oxidation.

PMID- 18335448
TI  - Photochromic, thermochromic, and fluorescent spirooxazines and naphthopyrans: a
      spectrokinetic and thermodynamic study.
AB  - The photochromic and thermochromic behavior of four commercially available
      Reversacol dyes are presented. The compounds studied belong to the class of
      spirooxazines and naphthopyrans, which are typically thermoreversible
      photochromic molecules. On stimulation with UV light, these compounds become
      colored and exhibit spectra which extend over the whole visible region.
      Increasing the temperature causes spontaneous coloration (thermochromism).
      Herein, absorption and fluorescence spectra, molar absorption coefficients of the
      colorless and colored forms, fluorescence and photochemical quantum yields, and
      kinetic parameters of thermal bleaching (rate constant, frequency factor, and
      activation energy) are determined in acetonitrile solution. The thermal ground
      state reaction is exhaustively described in terms of thermodynamic parameters
      (equilibrium constant, free energy, enthalpy, and entropy). Temperature effects
      on photochemical and thermal colorabilities are evaluated. The results indicate
      that the two spirooxazines are good photochromes below room temperature, whereas
      they are efficient thermochromic compounds above room temperature. Naphthopyrans
      are better photochromes but worse thermochromic compounds than spirooxazines.

PMID- 18335449
TI  - Re: A rebuttal: secret ties to industry and conflicting interests in cancer
      research, March, 2007; 50(3):227-233.

PMID- 18335450
TI  - The frontal bone skull post for image guided surgery of the nasopharynx.
AB  - BACKGROUND AND OBJECTIVES: To describe the use of the mastoid skull post of a
      surgical image guidance system for image guided surgery and intraoperative
      navigation of the nasopharynx. This adaptation overcomes the limitations of a
      headset frame or head clamp and can be applied to open and closed surgery of the
      nasal cavities, sinuses, orbits, midface and anterior skull base. METHODS: A
      sterile mastoid skull post of a surgical image guidance system was securely
      screwed into the outer table of the frontal bone and a passive reference frame
      fixed to it. The position of the reference frame relative to the patient's head
      remained constant during surgery. RESULTS: Between August 2002 and November 2006,
      22 patients underwent a surgical nasopharyngectomy using an image guidance system
      and frontal bone skull post. No surgical complications or complications of the
      frontal bone skull post occurred. CONCLUSION: Using the skull post of a surgical
      image guidance system anchored to the frontal bone to carry a passive reference
      frame provides real-time visual information about the relationship of relevant
      anatomy to the surgical field on a fully mobile head in open or closed procedures
      of the midface and anterior skull base while accuracy and sterility are
      maintained.

PMID- 18335451
TI  - Long-term pancreatic endocrine function following pancreatoduodenectomy with
      pancreaticogastrostomy.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate long-term
      pancreatic endocrine function following pancreatoduodenectomy with
      pancreaticogastrostomy. METHODS: Records of 52 patients who had survived for
      three or more years following pancreatoduodenectomy with pancreaticogastrostomy
      were studied retrospectively. Serum HbA(1c) levels had been measured prior to and
      at 3- to 6-month intervals after surgery. RESULTS: Three of 42 patients with
      normal preoperative serum HbA(1c) levels (<or=5.8%), and five of 10 patients with
      elevated preoperative serum HbA(1c) levels (>5.8%) showed deterioration of
      glucose tolerance. Five of these eight patients developed a pancreatic fistula
      postoperatively. However, the average serum HbA(1c) levels of patients with
      normal preoperative serum HbA(1c) levels have remained within the normal range
      for 3-10 years after surgery. CONCLUSIONS: Pancreatic endocrine function was
      maintained for a long-term period after pancreatoduodenectomy with
      pancreaticogastrostomy. Impaired glucose tolerance appeared to be associated with
      postoperative pancreatic fistula formation.

PMID- 18335452
TI  - Are buccal cancers in India and Canada any different?
AB  - BACKGROUND AND OBJECTIVE: To compare the treatment outcomes of squamous cell
      carcinoma (SCC) of buccal mucosa in India and Canada. METHODS: We compared the
      outcome of 169 patients with SCC of buccal mucosa treated at Tata Memorial
      Hospital (TMH), India with 64 matched patients from Cancer Care Manitoba (CCMB),
      Canada. Overall and cause specific survivals for the two geographical groups were
      calculated by Kaplan-Meir method and compared using log rank test. Cox regression
      analysis was used to see impact of independent variables. RESULTS: At 5 years,
      CCMB patients had lower over all survival (57.4% vs. 67.1%; P = 0.002) than TMH
      ones but similar cause specific survival (76.4% vs. 74.2%; P = 0.690). Age had an
      independent influence on both over all and cause specific survival. After
      adjusting for the age confounding in the Cox proportional hazard model there was
      no difference in the overall survival of the two groups (HR = 0.84; 95% CI =
      0.51, 1.40; P = 0.509). Radiated patients had three times higher risk of dying of
      disease than surgically treated ones (HR = 3.03; 95% CI = 1.64, 5.60; P < 0.001).
      CONCLUSIONS: There was no difference in the cause specific survival between the
      two groups. Apparent difference in the overall survival was due to the difference
      in the age of presentation.

PMID- 18335453
TI  - Impact of systemic inflammation on outcome following resection for intrahepatic
      cholangiocarcinoma.
AB  - AIMS: To analyse the results and prognostic factors affecting disease-free and
      overall survival following potentially curative resection for intrahepatic
      cholangiocarcinoma (IHCC). METHODS: Patients undergoing resection for IHCC from
      January 1996 to December 2006 were included. Data analysed included demographics,
      clinical and histopathology data. RESULTS: Twenty-seven patients were identified
      with a median age of 57 (32-84) years. The 1-, 3- and 5-year overall and disease
      free survival rates were 74%, 16% and 16%, and 44%, 15% and 15%, respectively. On
      univariate analysis, age <65 years, female gender, neutrophil to lymphocyte ratio
      (NLR) >or= 5, micro-vascular invasion and lymph node involvement were predictors
      of poorer overall survival. Multivariate analysis did not identify any
      independent predictors of overall survival. A NLR >or= 5 was the only adverse
      predictor of disease-free survival. The median disease-free survival of patients
      with NLR >or= 5 was 6 months compared to 18 months for those with NLR < 5. There
      was a significant association between patients with a NLR >or= 5 and larger
      tumour size, satellite lesions, micro-vascular invasion and lymph node
      involvement. CONCLUSION: Long-term outcome following resection of IHCC is poor. A
      pre-operative NLR >or= 5 was an adverse predictor of disease-free survival and
      was associated with an aggressive tumour biology profile.

PMID- 18335455
TI  - Developments in perforator imaging for the anterolateral thigh flap: CT
      angiography and CT-guided stereotaxy.
AB  - INTRODUCTION: The anterolateral thigh flap is an increasingly popular
      reconstructive option despite uncertainty in its perforator anatomy. Perforators
      are not always present, vary in size and intramuscular course, and have variable
      cutaneous courses and supply. As such, preoperative imaging has become favored.
      METHODS: The current study describes the preliminary use of two new modalities
      for preoperative imaging: computed tomography (CT) Angiography and CT-guided
      stereotaxy. These have been utilized in the preoperative imaging of two patients
      undergoing ALT flap reconstruction. Each patient underwent each of these
      techniques combined with Doppler ultrasound, the previous standard modality. The
      size, location, and course of perforators were explored and compared with
      operative findings. RESULTS: Both techniques are technically feasible, highly
      accurate, and provide more information to the surgeon than ultrasound.
      CONCLUSION: CT Angiography and CT-guided stereotaxy are useful adjuncts to
      Doppler ultrasound for imaging perforators prior to ALT flaps. A larger study is
      suggested to quantify the accuracy of these techniques.

PMID- 18335456
TI  - Synchronous reconstruction of the floor of mouth and chin with a single skin
      island fibular free flap.
AB  - OBJECTIVES: The goal this presentation is to: 1) Review the reconstructive
      options for anterior mandible through-and-through composite defects and 2)
      Instruct the audience in the application of the double-skin paddle fibular flap
      in selected patients. METHODS: Case presentation with review of the literature.
      RESULTS: A 70-year old male with an anterior floor of mouth squamous cell
      carcinoma underwent composite resection that included resection of a 5-cm ovoid
      component of overlying chin skin. The defect was reconstructed with a fibular
      osteocutaneous flap with a double skin paddle technique. CONCLUSIONS: Several
      reconstructive options have been described in the literature for extended oral
      cavity defects including the use of multiple free flaps, combinations of regional
      and distant flaps, and sequential reconstruction. This case report reviews the
      use of a single flap reconstruction of these defects for selected patients.

PMID- 18335457
TI  - Late free-flap salvage with catheter-directed thrombolysis.
AB  - INTRODUCTION: Despite high success rates with free-tissue transfer, flap loss
      continues to be a devastating event. Flap salvage is often successful if vascular
      complications are recognized and treated early. However, delayed presentation of
      flap compromise is an ominous predictor of flap loss. Late free-flap salvage has
      been described with poor long-term results. Catheter-directed thrombolysis (CDT)
      has only been described in context with free-tissue transfer in a case of distal
      bypass salvage. OBJECTIVES: The authors examined the efficacy of highly selective
      CDT in late salvage of free-flaps with vascular compromise. METHODS: Two patients
      underwent highly selective CDT after delayed presentation (>5 days) of flap
      compromise. Patient 1 is a 59-year-old woman who underwent delayed breast
      reconstruction with a free TRAM flap and presented with arterial thrombosis 12
      days postoperatively. Patient 2 is a 53-year-old man who underwent fibular
      osteocutaneous free-flap reconstruction of a floor of mouth defect who developed
      venous thrombosis 6 days postoperatively. Patient 2 underwent two attempted
      operative anastamotic revisions with thrombectomies and local thrombolysis prior
      to CDT. RESULTS: The average time of presentation was 9 days, with the average
      time to CDT being 9.5 days. Patient 1 had an arterial thrombosis, whereas Patient
      2 had a venous thrombosis. Both patients underwent successful thrombolysis after
      super-selective angiograms. Continuous infusions of thrombolytic agents were used
      in both patients for approximately 24 h. Average length of stay postCDT was 7
      days with no perioperative complications. Long-term follow-up demonstrated
      complete flap salvage with no soft tissue loss. CONCLUSION: Despite extremely
      delayed presentation, aggressive CDT was successful in both breast, and head and
      neck reconstructions with excellent long-term flap results. CDT appears to be a
      useful modality in managing difficult cases of free-flap salvage.

PMID- 18335458
TI  - The galectin family and digestive disease.
AB  - The soluble-type lectins or galectins constitute a family of proteins defined by
      shared consensus amino acid sequence and affinity for beta-galactose-containing
      oligosaccharides. These molecules are widely distributed in the animal kingdom;
      to date, 15 mammalian galectins have been described but more are likely to be
      discovered. These proteins are involved in many biological processes including
      cell-cell and cell-matrix adhesion, growth regulation, signaling, and cytokine
      secretion. Over the last decade, a vast amount of reports has shown the
      importance of several galectins in the development and progression of
      malignancies in the digestive tract, mainly colorectal cancers. More recent data
      indicate that some of these molecules are also involved in inflammatory bowel
      diseases. This review focuses on the current knowledge of galectin expression and
      putative functions in the oesophagus, stomach, small intestine, and colon. It
      also highlights that the rapid accumulation of research data promises future
      scenarios in which individual members of the galectin family and/or their ligands
      will be used as diagnostic and therapeutic modalities for neoplastic as well as
      inflammatory disorders. However, the concretization of these potential modalities
      requires substantial improvements in terms of standardization of galectin
      expression evaluation together with prospective validation of the present data.

PMID- 18335459
TI  - Recent developments in the molecular discrimination of formae speciales of
      Fusarium oxysporum.
AB  - Rapid and reliable detection and identification of potential plant pathogens is
      required for taking appropriate and timely disease management measures. For many
      microbial species of which all strains generally are plant pathogens on a known
      host range, this has become quite straightforward. However, for some fungal
      species this is quite a challenge. One of these is Fusarium oxysporum
      Schlechtend:Fr., which, as a species, has a very broad host range, while
      individual strains are usually highly host-specific. Moreover, many strains of
      this fungus are non-pathogenic soil inhabitants. Thus, with regard to effective
      disease management, identification below the species level is highly desirable.
      So far, the genetic basis of host specificity in F. oxysporum is poorly
      understood. Furthermore, strains that infect a particular plant species are not
      necessarily more closely related to each other than to strains that infect other
      hosts. Despite these difficulties, recently an increasing number of studies have
      reported the successful development of molecular markers to discriminate F.
      oxysporum strains below the species level.

PMID- 18335460
TI  - Factors influencing the association between active ingredient and adjuvant in the
      leaf deposit of adjuvant-containing suspoemulsion formulations.
AB  - BACKGROUND: For an oil adjuvant to enhance uptake of a particulate active
      ingredient (AI), it is hypothesised that closer association between the two
      should result in higher uptake. Accordingly, factors important for the spray
      deposit size on grapevine leaves have been investigated for a series of model
      suspoemulsion formulations containing colloidal crystalline AI or fluorescent
      pigment particles and an emulsion of an oil adjuvant with different degrees of
      wetting and different spray volumes. RESULTS: Low spray volumes (<100 L ha(-1))
      produced small deposits with high particle-adjuvant association. Complementary
      uptake studies showed increased uptake with decreasing deposit size, in agreement
      with the above hypothesis. Higher spray volumes produced larger deposits that
      consisted of annuli formed by pinning of the contact line by particles. Low
      surfactant concentrations favoured particles in the annulus and adjuvant
      separated in the centre. Intermediate surfactant concentrations produced annuli
      containing both particles and adjuvant, while with high surfactant concentrations
      the deposits were large with few annuli. CONCLUSIONS: Small deposits result in
      high AI-adjuvant association. With larger deposits, annulus structures allow for
      enhanced AI-adjuvant association (5-20 times greater). The formation of annuli
      appears to be important in enhancing the biodelivery of particulate AIs in
      adjuvant-containing suspoemulsion formulations at intermediate spray volumes.

PMID- 18335461
TI  - Whole-cell matrix-assisted laser desorption/ionization mass spectrometry for
      rapid identification of bacteriocin/lantibiotic-producing bacteria.
AB  - The potential of whole-cell matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) mass spectrometry (MS) for the discovery of microorganisms
      that produce lantibiotics and/or bacteriocins in the mass range 3-5 kDa is
      demonstrated. Cells of the antibiotic-producing model strain Bacillus subtilis
      ATCC 6633 were grown on Landy agar plates, and prepared with a 9:1 mixture of 2,5
      dihydroxybenzoic acid and 2-hydroxy-5-methoxybenzoic acid (DHBs) as matrix using
      the bottom-layer method. Time-course analyses showed that cells grown for 1-2
      days on agar plates gave the best results in terms of intensity of the
      bacteriocin/lantibiotic signals. Even after storage of matrix-crystal-embedded
      cells for several days high-resolution spectra (>10,000) could be obtained. To
      verify the applicability of this technique, different Bacillus wild-type and gene
      deletion mutant cells were analyzed. In most of the cases the known antibiotic
      phenotype of the producer could be corroborated by whole-cell MALDI-TOFMS,
      particularly for the lantibiotics subtilin and ericin. The preparation recipe for
      whole-cell analysis by MALDI-TOF was also highly sensitive for hydrophobic
      lipopeptide antibiotics like surfactin, mycosubtilin, fengycin, and bacillomycin
      in the lower mass range (1-1.5 kDa).

PMID- 18335462
TI  - Characterization of fatty acid esters of okadaic acid and related toxins in blue
      mussels (Mytilus edulis) from Norway.
AB  - Marine algal toxins of the okadaic acid group can occur as fatty acid esters in
      blue mussels, and are commonly determined indirectly by transformation to their
      parent toxins by alkaline hydrolysis. Some data are available regarding the
      identity of the fatty acid esters, mainly of palmitic acid (16:0) derivatives of
      okadaic acid (OA), dinophysistoxin-1 (DTX1) and dinophysistoxin-2 (DTX2). Other
      fatty acid derivatives have been described, but with limited mass spectral data.
      In this paper, the mass spectral characterization of the [M-H](-) and [M+Na](+)
      ions of 16 fatty acid derivatives of each of OA, DTX1 and DTX2 is presented. The
      characteristic fragmentation of [M+Na](+) ions of OA analogues provided a useful
      tool for identifying these, and has not been described previously. In addition, a
      set of negative ion multiple reaction monitoring (MRM) methods was developed for
      direct determination of 16 fatty acid esters of OA, 16 fatty acid esters of DTX1
      and 16 fatty acid esters of DTX2 in shellfish extracts. The MRM methods were
      employed to study the profiles of fatty acid esters of OA analogues in blue
      mussels and to compare these with fatty acid ester profiles reported for other
      groups of marine algal toxins.

PMID- 18335463
TI  - Sensitive detection of phosphopeptides by matrix-assisted laser
      desorption/ionization mass spectrometry: use of alkylphosphonic acids as matrix
      additives.
AB  - Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been
      one of the most powerful tools for analyzing protein phosphorylation. However, it
      is frequently difficult to detect phosphopeptides with high sensitivity by MALDI
      MS. In our investigation of matrix/matrix-additive substances for improving the
      phosphopeptide ion response in MALDI-MS, we found that the addition of low
      concentration alkylphosphonic acid to the matrix/analyte solution significantly
      enhanced the signal of phosphopeptides. In this study, the combination of
      methanediphosphonic acid and 2,5-dihydroxybenzoic acid gave the best results. In
      addition to enhancing the signal of the phosphopeptides, alkylphosphonic acid
      almost completely eliminated the signals of sodium and potassium ion adducts. We
      report herein sensitive detection of phosphopeptides by MALDI-MS with the use of
      alkylphosphonic acids as matrix additives.

PMID- 18335464
TI  - Rapid identification of differentiation markers from whole epithelial cells by
      matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry and
      statistical analysis.
AB  - Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry
      (MALDI-TOFMS) was applied to identify markers for cellular differentiation. The
      differentiation of a human colon epithelial carcinoma T84 cell line was monitored
      over a period of 28 days by transepithelial electrical resistance (TER)
      measurements, alkaline phosphatase (AP) assay, and MALDI-TOF mass spectral
      fingerprints combined with statistical analysis. MALDI-MS generated specific mass
      spectral fingerprints characteristic of cell differentiation. Twenty-two ions
      were selected as diagnostic signals of fully differentiated T84 cells. Ten
      protein ion signals, detected by MALDI-MS and validated by statistical analysis,
      were proposed as T84 cell differentiation markers. Among these signals, ubiquitin
      was identified as a T84 cell differentiation marker by nanospray liquid
      chromatography/tandem mass spectrometry (nanoLC/MS/MS). Moreover, depending on
      the concentration of the cells seeded on the growth support, it was possible to
      predict the timing of the exponential phase and of cellular differentiation by
      MALDI-MS-derived marker ions. MALDI-TOFMS was compared to other methods for the
      determination of cellular differentiation: TER measurements are rapid but yield
      limited information as to the cellular differentiation state. AP assays are more
      specific for the differentiation state but take more time. By contrast, MALDI-MS
      has been found to be a fast, sensitive and precise method for cell
      differentiation assessment and provides the opportunity for multiplexing and high
      throughput. Moreover, the consumable costs per assay are very low.

PMID- 18335465
TI  - Hydrolysis of thioesters in an ion trap.
AB  - The alkenyldiarylmethanes are a class of non-nucleoside reverse transcriptase
      inhibitors that are currently being developed as potential antivirals for the
      treatment of HIV infection and AIDS. As part of our continuing investigations on
      the alkenyldiarylmethanes, a series of thioester analogues were prepared in an
      effort to improve upon the metabolic stability of the parent lead compound.
      Hydrolysis of the thioester moieties was consistently observed during ion trap
      electrospray ionization (ESI) mass spectrometry to the extent that the parent
      molecular ion was weak in intensity or simply could not be detected. The same
      hydrolysis observations were also made when the analogues were analyzed by ion
      trap electron impact (EI) ionization, indicating the hydrolysis event was the
      result of the ion trap and not ionization technique. Ion-trap-mediated hydrolysis
      has been observed previously in prior alkenyldiarylmethane studies and prevented
      characterization of certain intermediates; thus, we wished to investigate whether
      modifying instrument parameters and protocols affected the instrument-mediated
      hydrolysis event. Unfortunately, varying the maximum injection time and the
      number of microscans performed, independent of each other, had little effect on
      the intensities of the parent ions [MH(+)] or the hydrolysis products] MH(+) 
      HSCH(3)].

PMID- 18335466
TI  - Rapid analysis of alpha-dicarbonyl compounds by laser desorption/ionization mass
      spectrometry using 9-(3,4-diaminophenyl)acridine (DAA) as a reactive matrix.
AB  - A rapid, sensitive and selective method has been developed for the analysis of
      alpha-dicarbonyls using a readily ionizable compound, 9-(3,4
      diaminophenyl)acridine (DAA), as a reactive matrix (derivatizing agent and
      ionization efficiency enhancer), by reactive matrix laser desorption/ionization
      time-of-flight mass spectrometry (RM-LDI-TOF MS). The reaction between the DAA
      and alpha-dicarbonyls resulted exclusively in formation of vacuum-stable
      dicarbonyl-quinoxaline acridine derivatives that were found to possess excellent
      ionization efficiency in positive ion mode, without the need to use an additional
      matrix. The alpha-dicarbonyls used as test compounds included methylglyoxal,
      dimethylglyoxal, and diphenylglyoxal. Both one-pot and rapid on-plate chemical
      modification approaches were employed with no extraction or purification
      necessary. The approach is particularly suitable for high-throughput analysis.
      The method was found to be selective and specific, with alpha-dicarbonyls
      unequivocally identified, even in complex matrices, e.g. beer. The figures of
      merit: relative standard deviation (RSD) 6.9-17%, (n = 4); limit of detection
      (LOD) < or =0.3 ng mL(-1) for the three standards tested using the one-pot
      derivatization method; and a good linear calibration curve using an internal
      standard derivatized in situ (R(2) > or = 0.979), demonstrate the applicability
      of the technique and its utility in improving the sensitivity and precision of
      the LDI analysis of small molecules.

PMID- 18335467
TI  - Detergent-free biotin switch combined with liquid chromatography/tandem mass
      spectrometry in the analysis of S-nitrosylated proteins.
AB  - High-throughput proteomic analysis based on a biotin switch combined with liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) enables simultaneous
      identification of S-nitrosylated sites and their cognate proteins in complex
      biological mixtures, which is a great help in elucidating the functions and
      mechanisms of this redox-based post-translational modification. However,
      detergents such as sodium dodecyl sulfate (SDS) and Triton X-100 adopted in these
      systems, which are hard to fully remove in the subsequent MS-based analyses, can
      suppress the peptide signals and influence the SNO-Cys site identification and
      the reproducibility of the experiments. Here we developed a detergent-free biotin
      switch method, which applied urea to replace detergents, and successfully
      combined it with LC/MS/MS in the analysis of S-nitrosylated proteins. With this
      approach, 44 SNO-Cys sites were specified on 35 distinct proteins in S
      nitrosoglutathione (GSNO)-treated HeLa cell extracts of proteins with good
      reproducibility. The LC/MS performance was greatly improved as analyzed with
      Pep3D and the amount of samples for analysis reduced from 40 mg used in the
      literature to 3-5 mg. For S-nitrosylated targets detected both in the control
      sample and in the GSNO-treated sample, extracted ion chromatography (XIC) was
      employed to estimate the quantitative change of S-nitrosylation (S-nitrosation),
      which facilitates the judgment on 'accept or reject' of the identified targets.

PMID- 18335468
TI  - Thigh muscle function in stroke patients revealed by velocity-encoded cine phase
      contrast magnetic resonance imaging.
AB  - Current methods of clinical assessment of muscle coordination and function after
      stroke do not provide information on deep muscles. The objective of this study
      was to examine how stroke affects both superficial and deep muscles' coordination
      and whether muscle function improves after rehabilitation. Muscle function,
      coordination, and activity of quadriceps femoris (QF) and hamstrings were
      evaluated in 10 stroke patients with mild hemiparesis and in 6 controls using
      velocity-encoded cine phase-contrast magnetic resonance imaging (VE-PC MRI),
      surface electromyography (sEMG), and maximal voluntary isometric contraction
      torque (MVC). At baseline, the peak muscle velocity of the rectus femoris (RF)
      and the ratio between the peak velocities of the RF and vasti were lower in the
      affected limb (AL) of stroke patients than in controls. Co-contraction of
      agonists and antagonists was higher in the AL than in controls. Muscle activity
      measured by sEMG showed similar behavior. After rehabilitation, the activity
      ratio of hamstrings and adductors to QF decreased slightly toward normal so there
      were no significant differences between the AL and controls. Impaired biarticular
      RF muscle function in stroke patients is the limiting factor during knee
      extension-flexion movements. After rehabilitation, improved functional
      performance was partly explained by the fact that the activities of the RF and
      vasti became more synchronized. VE-PC MRI can provide quantitative in vivo
      measurements of both superficial and deep muscles, and the information acquired
      after stroke can be utilized to render therapy more efficient and individually
      tailored.

PMID- 18335469
TI  - Sporadic bulbospinal muscle atrophy with facial-onset sensory neuropathy.
AB  - We report a case of idiopathic severe facial-onset sensorimotor neuropathy with
      no evidence of Kennedy's disease, familial amyotrophic lateral sclerosis,
      amyloidosis, Tangier disease, sarcoidosis, chronic basilar meningitis, or
      Sjogren's syndrome. Clinical and neurophysiological features of this patient
      resemble those of four recently reported patients who were affected with facial
      onset sensorimotor neuropathy (FOSMN), a probably novel disease. The present
      report provides information about a further patient with FOSMN in order to better
      characterize the clinical and laboratory features of this disease.

PMID- 18335470
TI  - Benefits of interval-training on fatigue and functional capacities in Charcot
      Marie-Tooth disease.
AB  - Exercise intolerance and undue fatigue are common complaints in patients with
      Charcot-Marie-Tooth (CMT) disease. Reduced physical ability is due directly to
      the disease, but it is also due to physical deconditioning. The aim of this study
      was to test whether 24 weeks of interval-training exercise (ITE) cycling can
      significantly improve physiological, neuromuscular, and functional capacities and
      alleviate fatigue in CMT patients. Eight CMT patients (4 CMT1A and 4 CMT2)
      participated in ITE for 3 nonconsecutive days per week. Cardiovascular fitness,
      muscle strength, fatigue resistance, and functional capacities were measured
      before and after 12 weeks of supervised hospital training and again after another
      12 weeks of unsupervised home training. Training was well tolerated. There were
      significant improvements in cardiorespiratory capacities, isokinetic concentric
      strength, and functional ability measurements. All patients experienced an
      improvement in their self-reported visual analogic scale for fatigue and pain
      during training. However, there was no significant change in their isometric
      force production and indices of fatigue resistance after training. Although the
      improvement in exercise tolerance may be due in part to reversal of the
      deconditioning effect of their related sedentary lifestyle, this clinical trial
      suggests that ITE can benefit CMT patients especially in their functional
      performance and subjective perception of pain and fatigue. Moreover, the
      improvement observed at the end of the first supervised period ITE was maintained
      after the second unsupervised home period, although there was no further
      improvement in performance and tolerance.

PMID- 18335471
TI  - Myotilin overexpression enhances myopathology in the LGMD1A mouse model.
AB  - Missense mutations in the myotilin gene cause limb-girdle muscular dystrophy type
      1A (LGMD1A). We set out to examine the effect of overexpression of wild-type
      myotilin in an LGMD1A mouse model by crossing wild-type and mutant transgenic
      mice. Compared to single-transgenic mutant mice, double-transgenic mice
      overexpressing myotilin showed more severe muscle degeneration, enhanced
      myofibrillar aggregation, and earlier onset of aggregation. These data suggest
      that strategies aimed at lowering total myotilin levels in LGMD1A patients may be
      an effective therapeutic approach.

PMID- 18335472
TI  - Quantification of biogenic amines in human plasma based on the derivatization
      with N-hydroxy-succinimidyl fluorescein-O-acetate by high-performance liquid
      chromatography.
AB  - An HPLC method for the determination of biogenic amines based on the precolumn
      derivatization with N-hydroxysuccinimidyl fluorescein-O-acetate (SIFA) has been
      developed. The derivatization was performed at 45 degrees C for 30 min in borate
      buffer (pH 8.0). The derivatives were separated on a ZORBAX Eclipse XDB-C8 column
      (150 mm x 4.6 mm id; 5 mum) and monitored by fluorescence detection (excitation,
      469 nm; emission, 512 nm). The LODs (S/N = 3) for spermine, spermidine,
      putrescine, cadaverine, and phenethylamine were 0.4, 0.2, 0.3, 0.5, and 0.4 nM,
      respectively. The developed method has been successfully applied to the
      determination of biogenic amines in human plasma of three healthy volunteers and
      four cancer patients. Average recoveries for plasma samples ranged from 94 to
      106% and coefficients of variation ranged from 1.8 to 4.6%. Deproteinization of
      plasma was accomplished with ACN to precipitate interfering substances and the
      centrifuged supernatant was used directly for analysis.

PMID- 18335473
TI  - Sensitive detection of tumor marker CA15-3 in human serum by capillary
      electrophoretic immunoassay with chemiluminescence detection.
AB  - A new and sensitive non-competitive immunoassay (IA) for tumor marker
      carbohydrate antigen 15-3 (CA15-3) by CE coupling with ECL detection has been
      developed. This method is based on luminol-H(2)O(2 )reaction catalyzed by
      horseradish peroxidase (HRP). The optimum CE separation and CL detection
      conditions were investigated. After the non-competitive immunoreaction, the free
      HRP-labeled CA15-3 antibody (Ab*) and the bound Ab*-antigen (Ab*-Ag) complex were
      separated in a separation capillary and then catalyzed the CL reaction of luminol
      and H(2)O(2 )in a reaction capillary following the separation capillary. The
      calibration curve based on the peak areas of Ab*-Ag complex plotted against the
      concentrations of CA15-3 is in the range of 0-250 U/mL with a correlation
      coefficient of 0.9983 and the detection limit is 0.035 U/mL (S/N = 3). The
      response for five consecutive injections of 125 U/mL CA15-3 resulted in RSDs of
      0.83% and 3.1% for the migration time and the peak area, respectively. The method
      was successfully used for the quantification of CA15-3 in human sera obtained
      from healthy persons and from patients with breast cancer.

PMID- 18335474
TI  - Separation of ternary systems of hydrophilic ionic liquid with miscible organic
      compounds by RPLC with refractive index detection.
AB  - A rapid and simple analytical method was developed for the simultaneous and
      quantitative determination and separation of hydrophilic imidazolium ionic
      liquids (ILs) (1-butyl-3-methylimidazolium chloride, [C(4)mim]Cl; 1-hexyl-3
      methylimidazolium chloride, [C(6)mim]Cl; 1-octyl-3-methylimidazolium chloride,
      [C(8)mim]Cl; 1-allyl-3-methylimidazolium chloride, [Amim]Cl; or 1-allyl-3
      methylimidazolium bromide, [Amim]Br) with miscible ethyl acetate and EtOH and
      their mixtures using reverse phase liquid chromatography coupled with refractive
      index detection (RPLC-RI). The influence of 60 to 100% (volume percentage)
      methanol in the mobile phase on the IL systems ([C(4)mim]Cl, [C(6)mim]Cl,
      [C(8)mim]Cl, [Amim]Br, or [Amim]Cl)-ethyl acetate-EtOH was investigated. The
      optimum mobile phase for the system [C(8)mim]Cl-ethyl acetate-EtOH, [C(4)mim]Cl
      ethyl acetate-EtOH, [Amim]Br-ethyl acetate-EtOH and [Amim]Cl-ethyl acetate-EtOH
      was methanol/water (60:40, v/v), and methanol/water (70:30, v/v) for [C(6)mim]Cl
      ethyl acetate-EtOH. Under optimum mobile phase conditions for each system, the
      RSD of the retention time ranged from 0.02 to 0.04%, and the RSDs of the peak
      area percent ranged from 0.23 to 1.85%, which showed good reproducibility of the
      RPLC-RI method. The RPLC-RI method can determine IL, ethyl acetate, and EtOH
      simultaneously in 5 min, and the analytes, especially IL, can be eluted
      completely. The results show that the RPLC-RI method can be used to separate and
      determine ILs in mixtures with organic compounds simultaneously and
      quantitatively.

PMID- 18335475
TI  - A quantitative peptide structure vs. retention relationship study.
AB  - The quantitative relationship between the TLC retention parameters of 28 short
      peptides and their physicochemical characteristics was calculated using linear
      regression analysis. It was established that surface parameters exert a
      significant impact on the retention of peptides and the ratio of non-polar
      surface area/polar surface area exerts the highest influence on the retention.
      This result may be due to the fact that peptides turn towards the apolar surface
      of the stationary phase with their non-polar substructures while the polar
      molecular parts point into the hydrophilic mobile phase.

PMID- 18335476
TI  - First ex-vivo MRI co-localization of two LIPOCEST agents.
AB  - One of the major advantages of the CEST methodology deals with the possibility of
      visualizing more probes in the same MR image voxels. This is a unique property
      within the contrast media that act on the (1)H-NMR signal of water protons, and
      it might considerably improve the potential of the technique. In addition to
      displaying sufficiently different resonance frequencies of their mobile protons,
      it is also important that the CEST agents designed for this application are
      highly sensitive. LIPOCEST agents represent the most sensitive class of CEST
      systems developed so far. On this basis, two LIPOCEST samples, a spherical one
      and an osmotically shrunken nonspherical one, endowed with markedly different
      resonance frequencies of their intraliposomal water protons, 3 ppm and 15 ppm,
      respectively, were prepared and tested both in vitro and in ex-vivo on a bovine
      muscle used as tissue-surrogate. The response of the two agents did not interfere
      each other, thus allowing the multiple visualization of the two agents present at
      nanomolar concentrations in the same image voxels.

PMID- 18335477
TI  - Efficient stem cell labeling for MRI studies.
AB  - Iron oxide particles are especially suited for cell tracking experiments due to
      their extraordinarily molar relaxivity as compared with other paramagnetic
      nuclei. We have compared different iron oxide particles (Sinerem, Endorem and
      magnetic microspheres) for their suitability to label embryonic stem cells (D3
      cell line). In addition to detectability thresholds, particular attention has
      been paid to the evaluation of long-term stability of the labelling procedure (up
      to 4 weeks) as well as to toxic and other adverse effects on cell viability.
      Comparative studies were performed using neural progenitor cells (C17.2) and
      dendritic cells. The present study indicates strong dependence of the label
      efficiency and stability on the iron oxide particles and cell lines in use.

PMID- 18335478
TI  - A dual CT-MR dendrimer contrast agent as a surrogate marker for convection
      enhanced delivery of intracerebral macromolecular therapeutic agents.
AB  - The feasibility of using Gd dendrimer-based macromolecules (Gd-G8 dendrimer) as a
      dual CT and MR contrast agent for monitoring convection-enhanced delivery of
      therapy in the brain is evaluated both in vitro and in vivo with optimal dosing
      established. In vitro CT attenuation values of the Gd-based agents (
      approximately 6.0 HU mM(-1)) were approximately 1.6 times greater than iodine
      based agents and the attenuation of the Gd-DTPA was comparable to Gd-G8
      dendrimer. Visible enhancement was observed on both CT and MR using Gd-G8
      dendrimer over a range of 23-78 mM; however, a concentration of at least 47 mM in
      Gd was required for adequate delineation of the injection site on both CT and MR.
      MR offers greater sensitivity than CT in estimating the volume of distribution
      (V(d)) and effectively quantified the agent's concentration and diffusion using
      T(1) mapping at much lower concentrations of Gd (<10 mM in [Gd]).

PMID- 18335479
TI  - Imaging of angiogenesis using Cadence contrast pulse sequencing and targeted
      contrast agents.
AB  - OBJECTIVES: Low-power multipulse contrast ultrasound imaging provides a promising
      tool to quantify angiogenesis noninvasively when used with contrast agents
      targeted to vascular markers expressed by the angiogenic endothelium. Targeted
      ultrasound contrast agents, with a diameter on the order of micrometers, cannot
      extravasate and therefore are targeted solely to receptors expressed by the
      vascular endothelium. The aim of this study was to evaluate the potential of a
      low-power multipulse imaging sequence, Cadence(TM) contrast pulse sequencing
      (CPS), combined with targeted contrast agents to quantify angiogenesis. MATERIAL
      AND METHODS: Targeted microbubbles were prepared by conjugating echistatin via
      biotin-avidin linkage to the surface of a phospholipid microbubble shell. The
      density of echistatin present on the shell was confirmed with flow-cytometry and
      quantified by total fluorescence. The binding of targeted microbubbles was
      evaluated in vitro by quantifying the adherence of targeted microbubbles to rat
      aortic endothelial cells, compared with control (nontargeted) microbubbles. The
      circulation time and adherence of targeted microbubbles was evaluated in vivo in
      a Matrigel model in rats and compared with control microbubbles using CPS in
      addition to a destructive ultrasound pulse. RESULTS: Using only the low-power CPS
      pulse, the echo intensity produced in the neovasculature of the Matrigel pellet
      was significantly greater with targeted microbubbles than with the control
      contrast agent (p < 0.001). Combining CPS with the destructive pulse, the
      processed image was significantly different in intensity (p < 0.001) and spatial
      extent between targeted and control agents (p < 0.001). When the morphology of
      the histological sample and ultrasound image correlated, the microvessel density
      count and the percentage of the circular area enhanced by ultrasound were
      correlated (p < 0.05). CONCLUSION: Low-power multipulse imaging in combination
      with targeted echistatin-bearing microbubbles facilitated a noninvasive,
      quantitative evaluation of early angiogenesis during real-time imaging. The
      addition of high-intensity destructive pulses facilitated estimation of the
      spatial extent of angiogenesis.

PMID- 18335481
TI  - Tissue Doppler imaging for detecting onset of muscle activity.
AB  - Tissue Doppler imaging (TDI) is typically used to image and quantify tissue
      motion. We investigated whether this method would serve as a viable alternative
      to surface electromyography (EMG) in providing a reliable and valid measure of
      the onset of muscle activity. Ten healthy subjects performed maximal knee
      extension exercises at 0 degrees /s (isometric), 60 degrees /s, 120 degrees /s,
      180 degrees /s, and 240 degrees /s (5 times each, on each side), using an
      isokinetic dynamometer. Simultaneous EMG and TDI velocity (superimposed on motion
      mode ultrasound cine-loops) recordings were made from vastus lateralis. All tests
      were repeated 1 week later. There was a good correlation between the onset times
      determined with TDI velocity and EMG: r = 0.78 (day 1), and r = 0.80 (day 2)
      (each P < 0.001). The mean difference (and SD) in muscle onset time between the
      two methods (TDI minus EMG) was -20.3 +/- 31.0 ms (day 1) and -17.4 +/- 27.2 ms
      (day 2). TDI represents a reliable and valid measure of detecting onset of muscle
      activity. The mean difference between EMG and TDI onset times (approximately 20
      ms) is likely explained by electromechanical delay. TDI represents a viable
      method for measuring the onset of muscle activity; it may offer a non-invasive
      alternative to fine-wire EMG for use with small or deep muscles.

PMID- 18335482
TI  - Pilot study of granulocyte colony stimulating factor (G-CSF)-mobilized peripheral
      blood stem cells in amyotrophic lateral sclerosis (ALS).
AB  - Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of upper and
      lower motor neurons in the brain, brainstem, and spinal cord. It has been
      proposed that bone marrow (BM)-derived cells might supply motor neurons and other
      cells with a cellular milieu more conducive to survival in ALS. Direct injection
      of stem cells in ALS is problematic because of the large expanse of the neuraxis
      that would need to be injected. We reasoned that transiently increasing the
      number of circulating hematopoietic stem cells might be a useful therapeutic
      approach. However, agents stimulating the activation and mobilization of
      hematopoietic stem cells may have adverse effects such as activation of
      microglial cells. We conducted a small pilot trial of the collection and
      reinfusion of granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral
      blood stem cells (PBSC) in ALS patients and found no adverse effects, paving the
      way for a properly powered therapeutic trial with an optimized regimen of G-CSF.

PMID- 18335483
TI  - Maximal versus submaximal intensity stimulation with variable patterns.
AB  - It is essential to determine optimal parameters of stimulation to maintain muscle
      force during neuromuscular electrical stimulation (NMES). Protocols that increase
      in frequency and include doublets can prolong force output over time. However,
      stimulation intensity level could differentially affect muscle force output
      during variable-frequency NMES. We compared three intermittent stimulation
      patterns at maximal and submaximal intensities of stimulation of the median
      nerve: (1) a constant 20-HZ pattern; (2) 90 s at 20 HZ followed by a 90-s
      increase from 20 to 40 HZ; and (3) 90 s at 20 HZ followed by 90 s of doublets at
      20 HZ. At submaximal intensities, the doublet pattern produced the highest
      overall force-time integral (FTI). At maximal intensities, the doublet pattern
      produced the lowest FTI and the increasing frequency pattern produced the least
      amount of fatigue. Thus, double-pulse stimulation was more effective during
      submaximal than maximal intensity NMES. These data demonstrate that intensity
      level must be taken into consideration when programming frequency patterns for
      NMES devices.

PMID- 18335484
TI  - Fast generation of nonresonant and resonant optical rotatory dispersion curves
      with the help of circular dichroism calculations and Kramers-Kronig
      transformations.
AB  - It can be computationally expensive to compute smooth, well resolved, optical
      rotation (OR) dispersion (ORD) curves from first principles theory. Instead of
      computing the OR at a large number of frequency points, similar results can be
      obtained by combined use of a computed circular dichroism (CD) spectrum along
      with a few OR calculations by using subtractive Kramers-Kronig transformations.
      We have tested various subtractive schemes for simulated (analytical) CD/ORD and
      for time-dependent density functional computations for dimethyloxirane, fenchone,
      and [4]triangulane. Nonresonant ORD can be obtained with as few as two OR and one
      CD calculation. For resonant ORD we found that between 7 and 15 OR computations
      plus the CD spectrum were typically sufficient, depending on the number of
      excitations within the frequency window of interest.

PMID- 18335485
TI  - Calculation of conformational energies and optical rotation of the most simple
      chiral alkane.
AB  - Quantum chemical calculations have been performed to investigate the conformer
      distribution of 4-ethyl-4-methyloctane and its optical rotation. With the
      reference methods MP2 and SCS-MP2, the energies of seven conformers are found
      within a range of about 1.5 kcal mol(-1). It is demonstrated that the relative
      energies cannot be reliably predicted with conventional GGA or hybrid density
      functionals, Hartree-Fock, semiempirical AM1, and classical force field (MM3)
      calculations. An empirical dispersion correction to GGA (PBE-D), hybrid (B3LYP
      D), or double hybrid (B2PLYP-D) functionals corrects these errors and results in
      very good agreement with the reference energies. Optical rotations have been
      calculated for all seven conformers at the TDDFT(BHLYP/aTZV2P) level. The
      computed macroscopic rotation is derived from a classical Boltzmann average. The
      result (1.9-3.2 deg dm(-1) (g/mL)(-1)) is very close to the experimental value of
      0.2 deg dm(-1) (g/mL)(-1) for the (R)-enantiomer and has the right sign. Because
      six conformers are significantly populated at room temperature and the rotations
      of individual conformers differ in sign and magnitude, the calculated average
      rotation is rather sensitive to the conformer population used. From the
      electronic structure point of view, this example emphasizes the effect of long
      range dispersion effects for the evaluation of population averaged quantities in
      large molecules. Computations based on free enthalpies are in worse agreement
      with experiment that is attributed to artefacts of the harmonic approximation
      used to compute the vibrational entropy terms.

PMID- 18335486
TI  - Re: Rahner et al. Coexisting somatic promoter hypermethylation and pathogenic
      MLH1 germline mutation in Lynch syndrome. J Pathol 2008; 214: 10-16.

PMID- 18335488
TI  - Vagal tone and temperament as predictors of emotion regulation strategies in
      young children.
AB  - We examined indices of vagal tone and two dimensions of temperament as predictors
      of emotion regulation (ER) strategies among children (n = 54, ages 4-7) of
      mothers with a history of depression and control mothers. Children's (adaptive
      and maladaptive) ER strategies were observed during a delay of gratification
      (frustration) task in one protocol. In a separate and independent protocol, vagal
      tone was assessed during rest (baseline), during emotional challenge (reactivity)
      and post-challenge (recovery) and mothers rated their children's temperament
      (effortful control, negative affectivity). Lower vagal recovery and higher
      negative affectivity were associated with maladaptive ER responses to
      frustration. However, vagal tone and temperament were not associated with
      adaptive ER responses and maternal depression status did not affect the results.
      Overall, the findings are consistent with models of vagal tone and temperament as
      markers of individual differences in ER.

PMID- 18335489
TI  - Intra-individual variability in infancy: structure, stability, and nutritional
      correlates.
AB  - Intra-individual variability (IIV) refers to relatively stable differences
      between individuals in the degree to which they show behavioral fluctuations over
      relatively short time periods. Using temperament as a conceptual framework the
      structure, stability, and biological roots of IIV were assessed over the first
      year of life. Biological roots were defined by maternal and infant nutrition. The
      sample was 249 Peruvian neonates, followed from the second trimester of pregnancy
      through the first 12 months of life. Maternal anthropometry, diet, iron status,
      and fetal growth were assessed prenatally. Neonatal anthropometry and iron status
      were assessed at birth. Degree of exclusive breastfeeding was assessed at 3 and 6
      months, infant anthropometry was assessed at 3, 6, and 12 months, infant dietary
      intake was assessed at 6 and 12 months and infant iron status was tested at 12
      months. Individual differences in IIV at 3, 6, and 12 months were derived from a
      residual standard deviation score based on infant behaviors measured using the
      Louisville Temperament Assessment Procedure. Principal components analysis
      indicated that individual differences in IIV were defined by two components at 3,
      6, and 12 months. There was modest stability between IIV components assessed at 3
      and 12 months. Reduced levels of IIV at 3 months were predicted by higher
      maternal weight and higher fetal weight gains in the first and second trimesters
      of pregnancy. Higher levels of IIV at 3 months were predicted by higher levels of
      maternal hemoglobin during pregnancy and higher levels of neonatal ferritin.

PMID- 18335491
TI  - Role and regulation of human XRCC4-like factor/cernunnos.
AB  - In mammalian cells, non-homologous end joining (NHEJ) is the major double strand
      break (DSB) repair mechanism during the G(1) phase of the cell cycle. It also
      contributes to DSB repair during the S and G(2) phases. Ku heterodimer, DNA PKcs,
      XRCC4 and DNA Ligase IV constitute the core NHEJ machinery, which joins directly
      ligatable ends. XRCC4-like factor/Cernunnos (XLF/Cer) is a recently discovered
      interaction partner of XRCC4. Current evidence suggests the following model for
      the role of XLF/Cer in NHEJ: after DSB induction, the XRCC4-DNA Ligase IV complex
      promotes efficient accumulation of XLF/Cer at DNA damage sites via constitutive
      interaction of the XRCC4 and XLF/Cer head domains and dependent on components of
      the DNA PK complex. Ku alone can stabilise the association of XLF/Cer with DNA
      ends. XLF/Cer stimulates ligation of complementary and non-complementary DNA ends
      by XRCC4-DNA Ligase IV. This activity involves the carboxy-terminal DNA binding
      region of XLF/Cer and could occur via different, non-exclusive modes: (i)
      enhancement of the stability of the XRCC4-DNA Ligase IV complex on DNA ends by
      XLF/Cer, (ii) modulation of the efficiency and/or specificity of DNA Ligase IV by
      binding of XLF/Cer to the XRCC4-DNA Ligase IV complex, (iii) promotion of the
      alignment of blunt or other non-complementary DNA ends by XLF/Cer for ligation.
      XLF/Cer promotes the preservation of 3' overhangs, restricts nucleotide loss and
      thereby promotes accuracy of DSB joining by XRCC4-DNA Ligase IV during NHEJ and
      V(D)J recombination.

PMID- 18335490
TI  - Timing of fetal exposure to stress hormones: effects on newborn physical and
      neuromuscular maturation.
AB  - The purpose of the study was to determine the specific periods during pregnancy
      in which human fetal exposure to stress hormones affects newborn physical and
      neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and
      31 weeks' gestation. Levels of placental corticotropin-releasing hormone (CRH)
      and maternal cortisol were determined from plasma. Newborns were evaluated with
      the New Ballard Maturation Score. Results indicated that increases in maternal
      cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were
      significantly associated with decreases in infant maturation among males (even
      after controlling for length of gestation). Results also suggested that increases
      in maternal cortisol at 31 weeks were associated with increases in infant
      maturation among females, although these results were not significant after
      controlling for length of gestation. Findings suggest that stress hormones have
      effects on human fetal neurodevelopment that are independent of birth outcome.

PMID- 18335492
TI  - Weak hand preference in children with down syndrome is associated with language
      deficits.
AB  - This study explores associations between language ability and hand preference in
      children with Down syndrome. Compared to typically developing children of the
      same age, children with Down syndrome showed weaker hand preference, were less
      consistent in the hand they used and also less willing to reach to extreme
      positions in contralateral space. Within the group of children with Down
      syndrome, those who showed a stronger or more consistent hand preference had
      better language and memory skills. This association could not be explained by
      differences in non-verbal cognitive ability or hearing loss. These findings are
      discussed within the theory of neurolinguistic development proposed by Locke
      [Locke (1997). Brain & Language, 58, 265-326].

PMID- 18335493
TI  - Physiological responses to social and cognitive challenges in 8-year olds with a
      history of prenatal cocaine exposure.
AB  - Cocaine-exposed infants have been found to have altered arousal responses but
      little is known about such responses in later childhood. Physiological responses
      to stressors were used to assess the arousal modulation of school-aged, cocaine
      exposed children (n = 73) and two contrast groups, socioeconomically-matched
      controls (n = 58) and children with behavioral disturbance (n = 35). The
      behaviorally disturbed group had the highest heart rate across conditions but
      demonstrated a pattern of hyporesponsiveness to the stressors. They had the
      smallest decrement in skin conductance response at baseline and the least
      recovery of skin conductance response following exposure to stressors. Cocaine
      exposed children demonstrated greater acceleratory responses to the stressors as
      indexed by their skin conductance level and were intermediate between the
      socioeconomically-matched controls and children with behavioral disturbance in
      recovery of skin conductance response following stressors. Altered arousal
      responses associated with prenatal cocaine exposure persisted into middle
      childhood but were different from those found in behaviorally disturbed children.

PMID- 18335494
TI  - Marked for life? Effects of early cage-cleaning frequency, delivery batch, and
      identification tail-marking on rat anxiety profiles.
AB  - Daily handling of preweanling rats reduces their adult anxiety. Even routine cage
      cleaning, involving handling, reduces adult anxiety compared with controls. Cage
      cleaning regimes differ between animal breeders, potentially affecting rodent
      anxiety and experimental results. Here, 92 adult male rats given different cage
      cleaning rates as pups, were compared on plus-maze, hyponeophagia,
      corticosterone, and handling tests. They were pair-housed and half were tail
      marked for identification. Anxiety/stress profiles were unaffected by cage
      cleaning frequency, suggesting that commercial-typical differences in husbandry
      contribute little variance to adult rat behavior. However, delivery batch
      affected some elevated plus-maze measures. Also, tail-marked rats spent three
      times longer on the plus-maze open arms than their unmarked cagemates, suggesting
      reduced anxiety, yet paradoxically they showed greater chromodacryorrhoea
      responses to handling, implying increased aversion to human contact. A follow-up
      study showed that rats avoided the odor released from the marker pen used. Thus,
      apparently trivial aspects of procedure can greatly affect experimental results.

PMID- 18335495
TI  - Development of object concepts in macaque monkeys.
AB  - One of the most interesting questions in cognitive development is how we acquire
      and mentally represent knowledge about objects. We investigated the development
      of object concepts in macaque monkeys. Monkeys viewed trajectory occlusion movies
      in which a ball followed a linear path that was occluded for some portion of the
      display while their point of gaze was recorded with a corneal-reflection eye
      tracker. We analyzed the pattern of eye movements as an indicator of object
      representation. A majority of eye movements of adult monkeys were anticipatory,
      implying a functional internal object representation that guided oculomotor
      behavior. The youngest monkeys lacked this strong internal representation of
      objects. Longitudinal testing showed that this ability develops over time
      providing compelling evidence that object concepts develop similarly in monkeys
      and humans. Therefore, the macaque monkey provides an animal model with which to
      examine neural mechanisms underlying the development of object representations.

PMID- 18335497
TI  - Developmental expression of NMDA and AMPA receptor subunits in vestibular nuclear
      neurons that encode gravity-related horizontal orientations.
AB  - We examined the expression profile of subunits of ionotropic glutamate receptors
      [N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole
      proprionate (AMPA)] during postnatal development of connectivity in the rat
      vestibular nucleus. Vestibular nuclear neurons were functionally activated by
      constant velocity off-vertical axis rotation, a strategy to stimulate otolith
      organs in the inner ear. These neurons indicated Fos expression as a result. By
      immunodetection for Fos, otolith-related neurons that expressed NMDA/AMPA
      receptor subunits were identified as early as P7, and these neurons were found to
      increase progressively up to adulthood. Although there was developmental
      invariance in the percentage of Fos-immunoreactive neurons expressing the NR1,
      NR2A, GluR1, or GluR2/3 subunits, those expressing the NR2B subunit decreased
      from P14 onward, and those expressing the GluR4 subunit decreased in adults.
      These double-immunohistochemical data were corroborated by combined immuno
      /hybridization histochemical data obtained from Fos-immunoreactive neurons
      expressing NR2B mRNA or GluR4 mRNA. The staining of both NR2B and GluR4 in the
      cytoplasm of these neurons decreased upon maturation. The percentage of Fos
      immunoreactive neurons expressing the other ionotropic glutamate receptor
      subunits (viz. NR1, NR2A, GluR1, and GluR2/3) remained relatively constant
      throughout postnatal maturation. Triple immunofluorescence further demonstrated
      coexpression of NR1 and NR2 subunits in Fos-immunoreactive neurons. Coexpression
      of NR1 subunit with each of the GluR subunits was also observed among the Fos
      immunoreactive neurons. Taken together, the different expression profiles of
      ionotropic glutamate receptor subunits constitute the histological basis for
      glutamatergic neurotransmission in the maturation of central vestibular
      connectivity for the coding of gravity-related horizontal head movements.

PMID- 18335498
TI  - Integrated analytical strategies for the study of phosphorylation and
      glycosylation in proteins.
AB  - The post-translational modification (PTM) of proteins is a common biological
      mechanism for regulating protein localization, function, and turnover. The direct
      analysis of modifications is required because they are not coded by genes, and
      thus are not predictable. Different MS-based proteomic strategies are used for
      the analysis of PTMs, such as phosphorylation and glycosylation, and are composed
      of a structural simplification step of the protein followed by specific isolation
      step to extract the classes of modified peptides (also called "sub-proteomes")
      before mass spectrometry. This specific isolation step is necessary because PTMs
      occur at a sub-stoichiometric level and signal suppression of the modified
      fractions in the mass spectrometer occurs in the presence of the more-abundant
      non-modified counterpart. The request of innovative analytical strategies in PTM
      studies is the capability to localize the modification sites, give detailed
      structural information on the modification, and determine the isoform composition
      with increased selectivity, sensitivity, and throughput. This review focuses on
      the description of recent integrated analytical systems proposed for the analysis
      of PTMs in proteins, and their application to profile the glycoproteome and the
      phosphoproteome in biological samples. Comments on the difficulties and
      usefulness of the analytical strategies are given.

PMID- 18335499
TI  - High-resolution genomic and expression analyses of copy number alterations in
      breast tumors.
AB  - Analysis of recurrent DNA amplification can lead to the identification of cancer
      driver genes, but this process is often hampered by the low resolution of
      existing copy number analysis platforms. Fifty-one breast tumors were profiled
      for copy number alterations (CNAs) with the high-resolution Affymetrix 500K SNP
      array. These tumors were also expression-profiled and surveyed for mutations in
      selected genes commonly mutated in breast cancer (TP53, CDKN2A, ERBB2, KRAS,
      PIK3CA, PTEN). Combined analysis of common CNAs and mutations revealed putative
      associations between features. Analysis of both the prevalence and amplitude of
      CNAs defined regions of recurrent alteration. Compared with previous array
      comparative genomic hybridization studies, our analysis provided boundaries for
      frequently altered regions that were approximately one-fourth the size, greatly
      reducing the number of potential alteration-driving genes. Expression data from
      matched tumor samples were used to further interrogate the functional relevance
      of genes located in recurrent amplicons. Although our data support the importance
      of some known driver genes such as ERBB2, refined amplicon boundaries at other
      locations, such as 8p11-12 and 11q13.5-q14.2, greatly reduce the number of
      potential driver genes and indicate alternatives to commonly suggested driver
      genes in some cases. For example, the previously reported recurrent amplification
      at 17q23.2 is reduced to a 249 kb minimal region containing the putative driver
      RPS6KB1 as well as the putative oncogenic microRNA mir-21. High-resolution copy
      number analysis provides refined insight into many breast cancer amplicons and
      their relationships to gene expression, point mutations and breast cancer subtype
      classifications. This article contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 18335500
TI  - Relationship between age and activity varies by sex in titi monkeys (Callicebus
      cupreus).
AB  - Motor activity increases during development and typically peaks before
      reproductive maturity. Males may become more active than do females, and this sex
      difference in activity may be a mechanism contributing to sex-biased dispersal.
      The generality of the link between sex differences in activity and sex
      differences in dispersal would be strengthened with evidence of greater female,
      as compared to male, activity during development in a species with a female bias
      in dispersal. Titi monkeys are a good model for such an investigation because
      subadult females leave their natal group at an earlier age than do subadult
      males. This study examines whether developing female titi monkeys become more
      active with age than do developing male titi monkeys. Locomotor activity of 13
      female and 8 male captive titi monkeys was measured as they matured from initial
      ambulatory independence (6 months of age) to reproductive maturity (24 months).
      Increased activity of females was associated most strongly with increasing age.
      Increased activity of males, however, was associated most strongly with repeated
      testing. Compared to maturing males, greater activity of maturing females may
      underlie the earlier dispersal of female titi monkeys that has been reported.

PMID- 18335501
TI  - The effects of early isolation on sexual behavior and c-fos expression in naive
      male Long-Evans rats.
AB  - Previous findings have demonstrated that the maternal environment is important
      for the development of male sexual behavior. The present study examined the
      effects of complete early life isolation and replacement 'stroking' stimulation
      on male sexual behavior and neural activation as seen by Fos immunoreactivity
      (Fos-IR). Animals were either artificially reared (AR) with minimal (AR-MIN) or
      maximal (AR-MAX) body simulation, or maternally reared (MR). In adulthood,
      animals were either given an exposure to an estrous female (EXP) or left
      undisturbed (NoEXP). No significant effects of early development were found in
      sexual behavior; however differences in activation in response to this exposure
      were observed. AR-MIN animals showed lower Fos-IR in the medial preoptic area and
      the ventromedial hypothalamus compared to MR animals. AR-MAX animals were not
      significantly different from either condition. These findings demonstrate that
      although there are no differences in the quality of the first copulatory exposure
      between AR and MR animals, the brain's response to this exposure differs in sites
      within the brain that subserve sexual behavior.

PMID- 18335502
TI  - Enriched environment restores impaired hippocampal long-term potentiation and
      water maze performance induced by developmental lead exposure in rats.
AB  - Lead (Pb2+) exposure in children can induce long lasting deficits in cognitive
      function and has been modeled in experimental animals. Based on previous studies
      which demonstrated that learning impairments resulting from developmental Pb2+
      exposure were reversible if the animals were provided with an enriched
      environment, here, we asked if environmental enrichment (EE) could also reverse
      long-term potential (LTP) impairment induced by lead. Rats drank 1,500 ppm lead
      acetate (PbAc) solution or distilled water throughout gestation and lactation.
      After weaning at postnatal Day 22, one half of the control and lead-exposed male
      offspring were given the environmental enrichment treatment through all the
      experiments until tested. Electrophysiological and Morris water maze test were
      performed at 8 weeks of age. The result showed that the impaired learning ability
      induced by lead could be reversed by EE. Furthermore, our results revealed that
      EPSP LTP and PS LTP impairments induced by lead were also reversible by EE
      experience.

PMID- 18335503
TI  - TGF-beta inhibits prolactin-induced expression of beta-casein by a Smad3
      dependent mechanism.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor,
      affecting cell proliferation, apoptosis, and extracellular matrix homeostasis. It
      also plays critical roles in mammary gland development, one of which involves
      inhibition of the expression of milk proteins, such as beta-casein, during
      pregnancy. Here we further explore the underlying signaling mechanism for it. Our
      results show that TGF-beta suppresses prolactin-induced expression of beta-casein
      mRNA and protein in primary mouse mammary epithelial cells, but its effect on
      protein expression is more evident. We also find out that this inhibition is not
      due to the effect of TGF-beta on cell apoptosis. Furthermore, inhibition of TGF
      beta type I receptor kinase activity by a pharmacological inhibitor SB431542 or
      overexpression of dominant negative Smad3 substantially restores beta-casein
      expression. By contrast, inhibition of p38 and Erk that are known to be activated
      by TGF-beta does not alleviate the inhibitory effect of TGF-beta. These results
      are consistent with our other observation that Smad but not MAPK pathway is
      activated by TGF-beta in mammary epithelial cells. Lastly, we show that prolactin
      induced tyrosine phosphorylation of Jak2 and Stat5 as well as serine/threonine
      phosphorylation of p70S6K and S6 ribosomal protein are downregulated by TGF-beta,
      although the former event requires considerably long exposure to TGF-beta. We
      speculate that these events might be involved in repressing transcription and
      translation of beta-casein gene, respectively. Taken together, our results
      demonstrate that TGF-beta abrogates prolactin-stimulated beta-casein gene
      expression in mammary epithelial cells through, at least in part, a Smad3
      dependent mechanism.

PMID- 18335504
TI  - The 10-Mb paracentric inversion of chromosome arm 2p in activating MSH2 and
      causing hereditary nonpolyposis colorectal cancer: re-annotation and mutational
      mechanisms.

PMID- 18335506
TI  - A PCR/restriction digestion assay for the detection of the transcript variants 1
      and 2 of POU5F1.
AB  - POU5F1 has two alternatively spliced transcripts: a long (variant 1, NM_002701)
      and a short (variant 2, NM_203289) transcript. Only variant 1 is a key regulator
      of pluripotency. Hence, it is important to be able to distinguish this transcript
      from variant 2 and from the many pseudogenes present in the genome. Previous
      studies on the expression of POU5F1 were, however, usually carried out without
      considering the existence of the two transcripts and the pseudogenes which could
      be the source of false positive RT-PCR amplification. Here, we establish an RT
      PCR/restriction digestion analysis to distinguish variant 1 of POU5F1 from
      variant 2 and all its currently known pseudogenes. Variant 1 has ApaI and Tsp45I
      restriction sites, which are not present in the pseudogenes or in variant 2.
      Thus, ApaI- and Tsp45I- digestions of POU5F1 PCR fragment, amplified with primers
      flanking these sites, are sufficient to identify the true variant 1 of POU5F1. To
      study the expression of variant 2 of POU5F1, two forward primers in the 5'-region
      that are not present in variant 1 were combined with reverse primers located in
      exon 3 of POU5F1 common to both transcripts. The assay was applied on 10 samples
      from peripheral blood leukocytes and commercially available ready-cDNAs from
      leukocytes and testis. We found that only variant 2 was expressed in leukocytes
      and testis and that the extracted RNA was not completely DNA free, despite DNAse
      treatment. This trace amount of DNA is a source of false positive RT-PCR
      amplifications. This article contains Supplementary Material available at
      http://www.interscience.wiley.com/jpages/1045-2257/suppmat.

PMID- 18335505
TI  - Identification of PAX3-FKHR-regulated genes differentially expressed between
      alveolar and embryonal rhabdomyosarcoma: focus on MYCN as a biologically relevant
      target.
AB  - Rhabdomyosarcoma is a family of myogenic soft tissue tumors subdivided into two
      main subtypes: alveolar (ARMS) and embryonal (ERMS). ARMS is characterized by a
      frequent 2;13 chromosomal translocation that creates a PAX3-FKHR fusion
      transcription factor. To identify downstream targets of PAX3-FKHR, we introduced
      an inducible form of PAX3-FKHR into human RD ERMS cells. Microarray analysis
      identified 39 genes (29 upregulated and 10 downregulated) that are modulated by
      PAX3-FKHR in RD cells and differentially expressed between ERMS and PAX3-FKHR
      positive ARMS tumors. Functional annotation demonstrated that genes involved in
      regulation of transcription and development, particularly neurogenesis, are
      represented in this group. MYCN was one notable neural-related transcription
      factor-encoding gene identified in this set, and its regulation by PAX3-FKHR was
      further confirmed at the RNA and protein levels. The findings of cycloheximide
      inhibition and time-course studies are consistent with the hypothesis that the
      PAX3-FKHR protein acts directly on the MYCN gene at the transcriptional level.
      Functional studies established that MYCN cooperates with PAX3-FKHR to enhance
      oncogenic activity. In conclusion, we identified a selected set of biologically
      relevant genes modulated by PAX3-FKHR, and demonstrated that PAX3-FKHR
      contributes to the expression of MYCN and in turn MYCN collaborates with PAX3
      FKHR in tumorigenesis.

PMID- 18335507
TI  - Effects of corticosterone deficiency and its replacement on Leydig cell
      steroidogenesis.
AB  - Clinical and experimental studies have shown the adverse effects of
      glucocorticoid deficiency/metyrapone treatment on testicular Leydig cell
      testosterone production. However, molecular mechanisms that underlie the effects
      of glucocorticoid deficiency on Leydig cell steroidogenesis are not yet
      determined. Therefore, the present study was designed to assess the mechanism of
      this phenomenon. Following metyrapone-induced corticosterone deficiency, serum
      testosterone, and Leydig cell 14C-glucose oxidation were decreased. StAR mRNA and
      protein levels were significantly increased in Leydig cells of corticosterone
      deficient animals. mRNA levels and the specific activities of P(450)scc and
      17beta-HSD were decreased by corticosterone deficiency, whereas the activity and
      mRNA of 3beta-HSD were increased. Simultaneous administration of corticosterone
      prevented its deficiency-induced changes in Leydig cells. Our results show that
      metyrapone-induced corticosterone deficiency impairs Leydig cell testosterone
      production by decreasing the activities of steroidogenic enzymes and their mRNA
      expression and glucose oxidation.

PMID- 18335508
TI  - Sonography in first trimester bleeding.
AB  - Vaginal bleeding is the most common cause of presentation to the emergency
      department in the first trimester. Approximately half of patients with first
      trimester vaginal bleeding will lose the pregnancy. Clinical assessment is
      difficult, and sonography is necessary to determine if a normal fetus is present
      and alive and to exclude other causes of bleeding (eg, ectopic or molar
      pregnancy). Diagnosis of a normal intrauterine pregnancy not only helps the
      physician in terms of management but also gives psychologic relief to the
      patient. Improved ultrasound technology and high-frequency endovaginal
      transducers have enabled early diagnosis of abnormal and ectopic pregnancies,
      decreasing maternal morbidity and mortality. The main differential considerations
      of first trimester bleeding are spontaneous abortion, ectopic pregnancy, or
      gestational trophoblastic disease. This article reviews the causes of first
      trimester bleeding and the sonographic findings, including normal features of
      first trimester pregnancy.

PMID- 18335509
TI  - Four-dimensional sonography with B-flow imaging and spatiotemporal image
      correlation for visualization of the fetal heart.
AB  - PURPOSE: To use B-flow imaging with 4-dimensional (4D) sonography and
      spatiotemporal image correlation (STIC) in the evaluation of normal fetal heart
      and congenital heart disease during pregnancy. METHOD: Volume data sets of the
      fetal heart were acquired with automated transverse and longitudinal sweeps of
      the anterior chest wall. We studied 13 normal fetuses and 2 fetuses with
      congenital heart disease (1 double-outlet right ventricle and 1 hypoplastic left
      heart syndrome) at gestation ages ranging from 13 to 39 weeks using
      transabdominal 4D B-flow sonography with STIC (4D BF-STIC). RESULTS: 4D BF-STIC
      demonstrated dynamic angiographic features in both normal and abnormal fetal
      hearts. 4D BF-STIC images could not be obtained in 2 normal fetuses at 18.1 and
      33.1 weeks because of the high fetal heart rate and inappropriate fetal position.
      In normal fetal heart, characteristic hemodynamic changes in both atria and
      ventricles were clearly demonstrated in systole and diastole. 4D BF-STIC also
      allowed visualization of the relationship, size, and course of the outflow
      tracts, thus helping the examiner to better understand the relationships between
      the vessels. In a case of hypoplastic left heart syndrome, dramatic hemodynamic
      changes including the right atrium, right ventricle, and pulmonary artery were
      evident. In a case of double-outlet right ventricle with ventricular septal
      defect, left-to-right shunt flow through a ventricular septal defect was clearly
      shown, as were great arteries originating in parallel from the right ventricle.
      CONCLUSION: 4D BF-STIC provides a means of real-time 3-dimensional evaluation of
      fetal intracardiac and extracardiac hemodynamics in the second and third
      trimesters. This novel technique assists in the evaluation of fetal cardiac
      hemodynamics and may play an important role in future fetal cardiac research and
      in the evaluation of congenital heart disease in the fetus.

PMID- 18335510
TI  - Internal jugular vein valve incompetence in COPD and primary pulmonary
      hypertension.
AB  - PURPOSE: Under physiologic conditions, intact internal jugular vein valves
      (IJVVs) efficiently prevent retrograde venous flow during intrathoracic pressure
      increase. Chronically elevated central venous pressure found in patients with
      chronic obstructive pulmonary disease (COPD) and primary pulmonary hypertension
      (PPH) might lead to IJVV incompetence (IJVVI). The aim of this study was to
      analyze the prevalence of IJVVI in patients with COPD and PPH using duplex
      sonography (DUS). METHOD: We included 30 COPD patients, 5 PPH patients, and 100
      healthy controls in the study. IJVVI was diagnosed if retrograde jugular blood
      flow was seen on DUS during a Valsalva maneuver. Retrograde venous flow intensity
      was evaluated and graded according to extent and duration of reflux. RESULTS:
      IJVVI was found in 18 (60%) COPD patients and in all 5 (100%) PPH patients, which
      was significantly different from the controls (27%; p < 0.005). The intensity of
      venous retrograde flow correlated with the pulmonary artery pressure. CONCLUSION:
      Compared with healthy controls, COPDand PPH patients demonstrated a
      significantlygreater prevalence of IJVVI, which seems to be caused by the
      elevated central venous pressure. These patients may be at higher risk to develop
      central nervous system diseases related to cerebral outflow obstruction.

PMID- 18335511
TI  - Abdominal aortic wall motion of healthy and hypertensive subjects: evaluation of
      tissue Doppler velocity imaging.
AB  - PURPOSE: To investigate the potential clinical application of tissue Doppler
      imaging (TDI) for motion measurement of the aortic wall in healthy and
      hypertensive adults. METHOD: We used TDI to examine 53 hypertensive and 29 sex
      matched healthy adults. Maximum velocity of the first and second systolic wall
      expansion peaks (S1, S2), maximum velocity of early (D) and end (E) diastolic
      retraction velocity peaks, pulse wave transmit time (PWTT), and stiffness index
      (beta) of the abdominal aorta were measured and compared as for factors
      influencing vascular compliance, including age, sex, and blood pressure. RESULTS:
      Compared with the healthy subjects, the wall motion waveform of hypertensive
      patients showed absent E, mixed S1 and S2 peaks, and blunted S1. S1 and D were
      lower in hypertensive than in healthy subjects. Shortened PWTT and increased
      indicated increased aortic stiffness in both male and female hypertensive subects
      when compared with controls. Age, diastolic blood pressure (DBP) and sex were the
      significant independent factors modulating S1, while DBP and age were the
      significant independent factors modulating D. PWTT was independently influenced
      by age and systolic blood pressure. CONCLUSION: This study provides evidence that
      abdominal aortic wall motion measurement with TDI could demonstrate qualitative
      and quantitative wall motion features differentiating hypertensive from healthy
      adults. Wall motion velocity and PWTT could reflect abdominal aortic compliance
      changes related to age, sex, and blood pressure.

PMID- 18335512
TI  - A Doppler waveform index to characterize hepatic vein velocity pattern and
      evaluate hepatic fibrosis.
AB  - PURPOSE: To describe a Doppler waveform index representing the hepatic vein flow
      velocity pattern and to examine its relationship to the degree of hepatic
      fibrosis. METHODS: Doppler waveforms were obtained in 66 patients scheduled for
      percutaneous liver needle biopsy and categorized as normal (with a retrograde
      flow phase) or abnormal (without retrograde flow). Waveforms were also
      characterized using a hepatic vein waveform index (HVWI): (maximum - minimum
      velocity)/(maximum velocity). Biopsy specimens were graded for fibrosis. RESULTS:
      There was a highly significant decrease in HVWI with increasing fibrosis score in
      the biopsy (p < 0.001, Jonckheere trend test). The biopsy showed cirrhosis in 14
      of 29 patients (48%) with absent retrograde flow and 5 of 37 patients (14%) with
      a normal flow pattern. Using HVWI as the criterion, cirrhosis was present in 13
      of 21 (62%) patients with HVWI < 0.75, in 6 of 31 (19%) patients with 0.75 < HVWI
      < 1.50, and in none of 14 (0%) patients with HVWI > 1.50. CONCLUSIONS: HVWI is
      inversely correlated to the degree of liver fibrosis and may be more efficient
      than the presence or absence of retrograde flow in diagnosing and grading hepatic
      fibrosis.

PMID- 18335513
TI  - Thickening of the gastric wall on transabdominal sonography: a sign of gastric
      cancer.
AB  - PURPOSE: To determine the value of a thickened gastric wall detected during
      transabdominal sonography (TAS) in the diagnosis of gastric cancer. METHOD: This
      prospective study comprised 312 patients who underwent both TAS and endoscopy.
      Transverse TAS scanning was performed using a 3.5-MHz curved transducer to
      measure gastric wall thickness in the antrum and body of the stomach. Based on
      endoscopic and histologic findings, we classified the patients into 3 groups:
      normal or benign disease (BD), early gastric cancer (EGC), and advanced gastric
      cancer (AGC). TAS findings were then compared. RESULTS: The thickness of the
      gastric wall was 4.9 +/- 1.6 mm in 262 patients with BD, 5.6 +/- 2.4 mm in
      21patients with EGC, and 10.3 +/- 4.7 mm in 29 patients with AGC (p < 0.01). A
      gastric wall thickness of greater than 7 mm had a 75.0% sensitivity, 92.6%
      specificity, 50.0% positive predictive value, and 97.4% negative predictive value
      in the diagnosis of AGC. CONCLUSION: Although not suitable as a screening method
      for gastric cancer, a thickening of the gastric wall of >7 mm may be a marker for
      AGC.

PMID- 18335514
TI  - Timing of Doppler examination for the detection of arteriovenous fistula after
      percutaneous renal biopsy.
AB  - Percutaneous renal biopsy is frequently performed, and postbiopsy arteriovenous
      fistula (AVF) formation is not uncommon. In most cases, it is asymptomatic and
      remains undiagnosed, because Doppler examination is not performed routinely. We
      describe 2 cases of postbiopsy AVF of the kidney that were detected 61 and 17
      months after renal biopsy, respectively. The subsequent superselective
      transcatheter arterial embolization was successful in both cases. An undetected
      AVF of the kidney can progress and lead to serious consequences. A follow-up
      Doppler examination of the kidney soon after renal biopsy and 6 months later is
      recommended for early detection of nonresolving AVFs to prevent further
      complications.

PMID- 18335515
TI  - A phase I/IItrial of MYO-029 in adult subjects with muscular dystrophy.
AB  - OBJECTIVE: Myostatin is an endogenous negative regulator of muscle growth and a
      novel target for muscle diseases. We conducted a safety trial of a neutralizing
      antibody to myostatin, MYO-029, in adult muscular dystrophies (Becker muscular
      dystrophy, facioscapulohumeral dystrophy, and limb-girdle muscular dystrophy).
      METHODS: This double-blind, placebo-controlled, multinational, randomized study
      included 116 subjects divided into sequential dose-escalation cohorts, each
      receiving MYO-029 or placebo (Cohort 1 at 1 mg/kg; Cohort 2 at 3 mg/kg; Cohort 3
      at 10 mg/kg; Cohort 4 at 30 mg/kg). Safety and adverse events were assessed by
      reported signs and symptoms, as well as by physical examinations, laboratory
      results, echocardiograms, electrocardiograms, and in subjects with
      facioscapulohumeral dystrophy, funduscopic and audiometry examinations.
      Biological activity of MYO-029 was assessed through manual muscle testing,
      quantitative muscle testing, timed function tests, subject-reported outcomes,
      magnetic resonance imaging studies, dual-energy radiographic absorptiometry
      studies, and muscle biopsy. RESULTS: MYO-029 had good safety and tolerability
      with the exception of cutaneous hypersensitivity at the 10 and 30 mg/kg doses.
      There were no improvements noted in exploratory end points of muscle strength or
      function, but the study was not powered to look for efficacy. Importantly,
      bioactivity of MYO-029 was supported by a trend in a limited number of subjects
      toward increased muscle size using dual-energy radiographic absorptiometry and
      muscle histology. INTERPRETATION: This trial supports the hypothesis that
      systemic administration of myostatin inhibitors provides an adequate safety
      margin for clinical studies. Further evaluation of more potent myostatin
      inhibitors for stimulating muscle growth in muscular dystrophy should be
      considered.

PMID- 18335516
TI  - An innovative molybdenum column liner for oxygen and hydrogen stable isotope
      analysis by pyrolysis.
AB  - The most widely used method for pyrolysing samples for hydrogen or oxygen
      isotopic analysis involves heating them to greater than 1300 degrees C in a
      helium stream passed through a glassy carbon tube in an alumina casing. There are
      a number of difficulties with this. Glassy carbon tubes are expensive and
      interaction between the carbon tube and the outer casing produces unwanted carbon
      monoxide by reduction of the alumina at high temperatures. The latter effect is
      overwhelming if temperatures of 1400 degrees C or greater are used for pyrolysis.
      We experimented with lining alumina casings with pure molybdenum sheet. It is
      relatively cheap, conforms well to the interior of the reactor tube (to avoid
      carrier and sample bypassing of the carbon pack), resists high temperatures and
      neither oxidises excessively nor absorbs the gases. The main disadvantages are
      that silver sample cups must be used and that the molybdenum degrades over time
      by formation of the carbide. We can maintain sharp peaks, high precision and good
      accuracy over more than 700 solid samples for both hydrogen and oxygen. The
      reactors last longer for water injections. The molybdenum in the columns does not
      contribute greatly to memory effects. The precision of analysis is dependent on
      other factors as well as the pyrolysis column, but for oxygen we typically
      achieve approximately <0.2 per thousand (sucrose), <0.25 per thousand (water) and
      <0.25 per thousand (leaf), sometimes using only a linear correction of drift,
      after dividing the run into 1 to 3 segments.

PMID- 18335518
TI  - Nonmotor symptoms in Parkinson's disease: investigating early-phase onset of
      behavioral dysfunction in the 6-hydroxydopamine-lesioned rat model.
AB  - To investigate the psychiatric symptoms accompanying the early phases of
      Parkinson's disease (PD), we injected adult rats with 10.5 microg 6
      hydroxydopamine (6-OHDA) bilaterally into the dorsal striatum. The resulting
      neurodegeneration led, 12 weeks after injection, to a mild (36%) reduction of
      striatal dopamine. We tested the behavioral response of sham and 6-OHDA-lesioned
      animals at different time points after injection to evaluate the onset and
      progression of behavioral abnormalities. The results showed that such a mild
      reduction of dopamine levels was associated with a decrease in anxiety-like
      behavior, an increase in "depression"-like behavior, and a marked change in
      social behavior. Learning and memory abilities were not affected. Overall, the PD
      rat model used here displays behavioral alterations having face validity with
      psychiatric symptoms of the pathology and thus appears to be a valuable tool for
      investigating the neural bases of the early phases of PD.

PMID- 18335517
TI  - Manganese potentiates nuclear factor-kappaB-dependent expression of nitric oxide
      synthase 2 in astrocytes by activating soluble guanylate cyclase and
      extracellular responsive kinase signaling pathways.
AB  - Inflammatory activation of glial cells is associated with neuronal injury in
      several degenerative movement disorders of the basal ganglia, including manganese
      neurotoxicity. Manganese (Mn) potentiates the effects of inflammatory cytokines
      on nuclear factor-kappaB (NF-kappaB)-dependent expression of nitric oxide
      synthase 2 (NOS2) in astrocytes, but the signaling mechanisms underlying this
      effect have remained elusive. It was postulated in the present studies that
      direct stimulation of cGMP synthesis and activation of mitogen-activated protein
      (MAP) kinase signaling pathways underlies the capacity of Mn to augment NF-kappaB
      dependent gene expression in astrocytes. Exposure of primary cortical astrocytes
      to a low concentration of Mn (10 microM) potentiated expression of NOS2 mRNA and
      protein along with production of NO in response to interferon-gamma (IFNgamma)
      and tumor necrosis factor-alpha (TNFalpha), which was prevented by overexpression
      of dominant negative IkappaB alpha. Mn also potentiated IFNgamma- and TNFalpha
      induced phosphorylation of extracellular response kinase (ERK), p38, and JNK, as
      well as cytokine-induced activation of a fluorescent NF-kappaB reporter construct
      in transgenic astrocytes. Activation of ERK preceded that of NF-kappaB and was
      required for maximal activation of NO synthesis. Independently of
      IFNgamma/TNFalpha, Mn-stimulated synthesis of cGMP in astrocytes and inhibition
      of soluble guanylate cyclase (sGC) abolished the potentiating effect of Mn on MAP
      kinase phosphorylation, NF-kappaB activation, and production of NO. These data
      indicate that near-physiological concentrations of Mn potentiate cytokine-induced
      expression of NOS2 and production of NO in astrocytes via activation of sGC,
      which promotes ERK-dependent enhancement of NF-kappaB signaling.

PMID- 18335519
TI  - Role of protein kinase Cdelta in paraquat-induced glial cell death.
AB  - Paraquat (1,1'-dimethyl-4,4'-bipyridinium) is structurally similar to the
      neurotoxin 1-methyl-4-phenyl-4-phenylpyridium ion (MPP+), the active metabolite
      of the parkinsonism-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
      (MPTP), which can induce the parkinsonism property in rodents, nonhuman primates,
      and human. In contrast to the neurotoxic effects of paraquat, little is known
      about its effects on glial cells. Here, we examined the mechanisms of paraquat
      toxicity in glial cells in culture. Paraquat treatment also reduced the viability
      of C6 glial cells in primary astrocyte cultures, and cell death was mostly
      apoptotic in nature. PKCdelta played a central role in the paraquat-induced glial
      cell death: (1) the PKCdelta-specific inhibitor rottlerin blocked paraquat
      induced glial cell death; (2) paraquat induced tyrosine and threonine
      phosphorylation of PKCdelta; and (3) transfection of the dominant-negative mutant
      of PKCdelta attenuated paraquat toxicity. PKCdelta was also involved in the
      generation of reactive oxygen species (ROS), which mediated the paraquat
      toxicity. The nicotinamide adenine dinucleotide phosphate (reduced form) oxidase
      (NADPH oxidase) inhibitor diphenyleneiodonium blocked the paraquat-induced ROS
      production and subsequent cell death, indicating the involvement of NADPH oxidase
      in the cytotoxic action of paraquat in glia. PKCdelta was also important in glial
      cell death induced by MPP+ but not in that induced by rotenone. Last, Rac1
      appeared to antagonize paraquat toxicity in glia. These results indicate a
      gliotoxic effect of paraquat and an opposing role of PKCdelta and Rac1 in
      paraquat-induced glial cell death.

PMID- 18335520
TI  - Advanced glycation end products induce in vitro cross-linking of alpha-synuclein
      and accelerate the process of intracellular inclusion body formation.
AB  - Cross-linking of alpha-synuclein and Lewy body formation have been implicated in
      the dopaminergic neuronal cell death observed in Parkinson's disease (PD); the
      mechanisms responsible, however, are not clear. Reactive oxygen species and
      advanced glycation end products (AGEs) have been found in the intracellular,
      alpha-synuclein-positive Lewy bodies in the brains of both PD as well as
      incidental Lewy body disease patients, suggesting a role for AGEs in alpha
      synuclein cross-linking and Lewy body formation. The aims of the present study
      were to determine 1) whether AGEs can induce cross-linking of alpha-synuclein
      peptides, 2) the progressive and time-dependent intracellular accumulation of
      AGEs and inclusion body formation, and 3) the effects of extracellular or
      exogenous AGEs on intracellular inclusion formation. We first investigated the
      time-dependent cross-linking of recombinant human alpha-synuclein in the presence
      of AGEs in vitro, then used a cell culture model based on chronic rotenone
      treatment of human dopaminergic neuroblastoma cells (SH-SY5Y) over a period of 1
      4 weeks, in the presence of different doses of AGEs. Cells (grown on coverslips)
      and cell lysates, collected at the end of every week, were analyzed for the
      presence of intracellular reactive oxygen species, AGEs, alpha-synuclein
      proteins, and intracellular alpha-synuclein- and AGE-positive inclusion bodies by
      using immunocytochemical, biochemical, and Western blot techniques. Our results
      show that AGEs promote in vitro cross-linking of alpha-synuclein, that
      intracellular accumulation of AGEs precedes alpha-synuclein-positive inclusion
      body formation, and that extracellular AGEs accelerate the process of
      intracellular alpha-synuclein-positive inclusion body formation.

PMID- 18335521
TI  - Transient 5-(4-phenylbutoxy)psoralen (PAP-1) treatment dissociates developing
      pathologies in autoimmune optic neuritis into two distinct pathology profiles.
AB  - Discovery of treatments to protect axonal function of neurons and prevent
      permanent disability associated with progressive multiple sclerosis (MS) has
      faced the uphill challenge of assessing relatively small changes in accumulated
      axon damage within a background environment that is disorganized by CNS
      inflammation. We hypothesized that transient immunosuppression after initiation
      of MS-like autoimmune mechanisms would disassociate development of MS-like
      myelinated axon pathology from development of CNS inflammation in a rat model of
      autoimmune optic neuritis (AON). A rat model of myelin oligodendrocyte
      glycoprotein peptide-induced AON was transiently treated (on days 3-7 after
      antigen exposure) with 5-(4-phenylbutoxy)psoralen (PAP-1), an immunomodulatory
      drug previously shown specifically to suppress proliferation of effector memory T
      cells and immunoglobulin class-switched B-cells. Thirteen days after antigen
      exposure, optic nerves were harvested for quantitative assessment of 12 MS
      associated pathologies using microfluorimetry. With one exception, the
      immunoreactivities (-ir) for eight markers of MS-like neuroinflammation and
      immune infiltration were significantly reduced (P < 0.05) by transient PAP-1
      treatment, often to levels significantly below those detected in normal control
      rat optic nerves. With one exception, four immunoreactive markers of MS-like
      myelinated axon pathology were detected at levels indicating increased
      axon/myelin pathology compared with vehicle-treated rats with AON (P < 0.05).
      These data suggest the conclusion that early causative mechanisms in CNS
      autoimmunity initiate signaling mechanisms that diverge into two separate
      pathways, one that is strongly associated with inflammatory responses and one
      that is associated predominantly with disturbed axon-myelin interactions and
      impaired fast axonal transport.

PMID- 18335522
TI  - Adult human spinal cord harbors neural precursor cells that generate neurons and
      glial cells in vitro.
AB  - Adult human and rodent brains contain neural stem and progenitor cells, and the
      presence of neural stem cells in the adult rodent spinal cord has also been
      described. Here, using electron microscopy, expression of neural precursor cell
      markers, and cell culture, we investigated whether neural precursor cells are
      also present in adult human spinal cord. In well-preserved nonpathological post
      mortem human adult spinal cord, nestin, Sox2, GFAP, CD15, Nkx6.1, and PSA-NCAM
      were found to be expressed heterogeneously by cells located around the central
      canal. Ultrastructural analysis revealed the existence of immature cells close to
      the ependymal cells, which display characteristics of type B and C cells found in
      the adult rodent brain subventricular region, which are considered to be stem and
      progenitor cells, respectively. Completely dissociated spinal cord cells
      reproducibly formed Sox2(+) nestin(+) neurospheres containing proliferative
      precursor cells. On differentiation, these generate glial cells and gamma
      aminobutyric acid (GABA)-ergic neurons. These results provide the first evidence
      for the existence in the adult human spinal cord of neural precursors with the
      potential to differentiate into neurons and glia. They represent a major interest
      for endogenous regeneration of spinal cord after trauma and in degenerative
      diseases.

PMID- 18335523
TI  - Folic acid deficiency increases delayed neuronal death, DNA damage, platelet
      endothelial cell adhesion molecule-1 immunoreactivity, and gliosis in the
      hippocampus after transient cerebral ischemia.
AB  - Folic acid deficiency increases stroke risk. In the present study, we examined
      whether folic acid deficiency enhances neuronal damage and gliosis via oxidative
      stress in the gerbil hippocampus after transient forebrain ischemia. Animals were
      exposed to a folic acid-deficient diet (FAD) for 3 months and then subjected to
      occlusion of both common carotid arteries for 5 min. Exposure to an FAD increased
      plasma homocysteine levels by five- to eightfold compared with those of animals
      fed with a control diet (CD). In CD-treated animals, most neurons were dead in
      the hippocampal CA1 region 4 days after ischemia/reperfusion, whereas, in FAD
      treated animals, this occurred 3 days after ischemia/reperfusion. Immunostaining
      for 8-hydroxy-2'-deoxyguanosine (8-OHdG) was performed to examine DNA damage in
      CA1 neurons in both groups after ischemia, and it was found that 8-OHdG
      immunoreactivity in both FAD and CD groups peaked at 12 hr after reperfusion,
      although the immunoreactivity in the FAD group was much greater than that in the
      CD group. Platelet endothelial cell adhesion molecule-1 (PECAM-1; a final
      mediator of neutrophil transendothelial migration) immunoreactivity in both
      groups increased with time after ischemia/reperfusion: Its immunoreactivity in
      the FAD group was much higher than that in the CD group 3 days after
      ischemia/reperfusion. In addition, reactive gliosis in the ischemic CA1 region
      increased with time after ischemia in both groups, but astrocytosis and
      microgliosis in the FAD group were more severe than in the CD group at all times
      after ischemia. Our results suggest that folic acid deficiency enhances neuronal
      damage induced by ischemia.

PMID- 18335524
TI  - ER stress is involved in Abeta-induced GSK-3beta activation and tau
      phosphorylation.
AB  - Intracellular neurofibrillary tangles, one of the characteristic hallmarks of
      Alzheimer's disease (AD), are mainly composed of hyperphosphorylated tau. The
      abnormal tau phosphorylation seems to be related to altered activity of kinases
      such as glycogen synthase kinase-3beta (GSK-3beta). Tau pathology is thought to
      be a later event during the progression of the disease, and it seems to occur as
      a consequence of amyloid-beta (Abeta) peptide accumulation. The aim of this work
      was to investigate whether soluble Abeta1-42, particularly oligomers that
      correspond to the neurotoxic species involved early in the development of AD,
      triggers tau phosphorylation by a mechanism involving activation of tau-kinase
      GSK-3beta. Several studies suggest that GSK-3beta plays a central role in
      signaling the downstream effects of endoplasmic reticulum (ER) stress. Therefore,
      the involvement of ER Ca(2+) release in GSK-3beta activation and tau
      phosphorylation induced by Abeta1-42 oligomers was evaluated using dantrolene, an
      inhibitor of Ca(2+) release through channels associated with ER ryanodine
      receptors. We observed that Abeta1-42 oligomers increase tau phosphorylation and
      compromises cell survival through a mechanism mediated by GSK-3beta activation.
      We also demonstrated that oligomeric Abeta1-42 induces ER stress and that ER
      Ca(2+) release is involved in oligomer-induced GSK-3beta activation and tau
      phosphorylation. This work suggests that GSK-3beta can be a promising target for
      therapeutic intervention in AD.

PMID- 18335525
TI  - Immune or inflammatory response by the host brain suppresses neuronal
      differentiation of transplanted ES cell-derived neural precursor cells.
AB  - Embryonic stem (ES) cells are a promising donor source for transplantation
      therapy, but several problems must be solved before they can be clinically
      useful. One of these is the host immune reaction to allogeneic grafts. In this
      article, we examine the effect of the host immune reaction on survival and
      differentiation of grafted ES cell-derived neural precursor cells (NPCs). We
      induced NPCs from mouse ES cells by stromal cell-derived inducing activity and
      then transplanted them into mouse brains with or without administering the
      immunosuppressant cyclosporine A (CsA). Two and 8 weeks following
      transplantation, the accumulation of host-derived microglia/macrophages and
      lymphocytes was observed around the graft. This effect was reduced by CsA
      treatment, although no significant difference in graft volume was observed. These
      data suggest that an immune response occurs in allografts of ES cell-derived
      NPCs. Intriguingly, however, the ratio of neurons to astrocytes in the graft was
      higher in immunosuppressed mice. Because inflammatory or immune cells produce
      various cytokines, we examined the effect of IL-1beta, IL-6, IFN-gamma, and TNF
      alpha on the differentiation of NPCs in vitro. Only IL-6 promoted glial cell
      fate, and this effect could be reversed by the addition of an IL-6 neutralizing
      antibody. These results suggest that allogeneic ES cell-derived NPCs can cause an
      immune response by the host brain, but it is not strong enough to reject the
      graft. More important, activated microglia and lymphocytes can suppress neuronal
      differentiation of grafted NPCs in vivo by producing cytokines such as IL-6.

PMID- 18335526
TI  - Prevalence of genes for aminoglycoside-modifying enzymes in Staphylococcus
      epidermidis isolates from orthopedic postsurgical and implant-related infections.
AB  - Staphylococcus epidermidis, a main etiologic agent of implant-related infections,
      is showing increasing resistance to several antibiotic substances, among them the
      aminoglycosides, a class of drugs playing a relevant role in current medical
      protocols to prevent and treat clinical infections. Here we investigated the
      prevalence of aac(6')-Ie-aph(2''), aph(3')-IIIa, and ant(4') genes, encoding for
      the three forms of aminoglycoside-modifying enzymes (AME), responsible for
      resistance to aminoglycoside antibiotics, in 70 clinical isolates of S.
      epidermidis from orthopedic postsurgical and implant-related infections. In
      addition, ermA and ermC, the two most common staphylococcal genes conferring
      antibiotic resistance to macrolides, lincosamides, and streptogramin B (MLS(B))
      were included in this investigation. All isolates were characterized by automated
      ribotyping, so that the presence of antibiotic resistance determinants was
      investigated in strains exhibiting different ribopatterns. Interestingly,
      combinations of coexisting AME genes appeared to be typical of specific
      ribopatterns. The aac(6')-Ie-aph(2'') gene was the most prevalent AME gene, being
      observed in 44% of the isolates. As far as the determinants for MLS(B)
      antibiotics are concerned, the ermC gene was observed in 33% of the isolates,
      while ermA was detected in a single isolate. These results provide a detailed
      characterization in terms of antibiotic resistance determinants of clones of S.
      epidermidis frequently isolated from implant orthopedic infections, providing
      useful indications for more effectual future strategies of infection
      prevention/eradication based on the incorporation of antibiotic drugs in
      biomaterials.

PMID- 18335527
TI  - p53 reaction to apoptosis induced by hydroxyapatite nanoparticles in rat
      macrophages.
AB  - The effects and mechanism of hydroxyapatite (HAP) nanoparticles (NPs) on the
      induction of cytotoxicity and apoptosis in rat macrophages was evaluated by
      testing the antiproliferative effect of HAP NPs with agar overlay and direct
      contact methods. The apoptotic phenotype of the macrophages was observed by
      transmission electron microscopy (TEM), and the variation of transcription and
      expression of a cell apoptosis related gene (p53) was determined by
      semiquantitative RT-PCR and western blotting. The results showed that a dose
      dependent proliferative inhibition of macrophages was induced by HAP NPs (30-80
      nm) at concentrations between 20 and 200 microg/mL. The characteristic
      morphological changes of apoptosis were observed in macrophages after treatment
      with HAP NPs for 24 h. Furthermore, p53 mRNA levels significantly increased when
      macrophages were incubated with 200 microg/mL HAP NPs (p < 0.01). Western blot
      analysis showed that 100 microg/mL HAP NPs upregulated p53. The conclusion is
      that HAP NPs can induce p53 expression through phosphorylation, which promotes
      downstream genes and finally results in cell apoptosis. Moreover, p53 may be one
      of the ideal indictors to evaluate the biological safety of ceramic
      nanoparticles.

PMID- 18335528
TI  - Processing, characterization, and in vitro/in vivo evaluations of powder
      metallurgy processed Ti-13Nb-13Zr alloys.
AB  - This article presents details of processing, characterization and in vitro as
      well as in vivo evaluations of powder metallurgy processed Ti-13Nb-13Zr samples
      with different levels of porosity. Sintered samples were characterized for
      density, crystalline phases (XRD), and microstructure (SEM and EDX). Samples
      sintered at 1000 degrees C showed the highest porosity level ( approximately
      30%), featuring open and interconnected pores ranging from 50 to 100 mum in
      diameter but incomplete densification. In contrast, samples sintered at 1300 and
      1500 degrees C demonstrated high densification with 10% porosity level
      distributed in a homogeneous microstructure. The different sintering conditions
      used in this study demonstrated a coherent trend that is increase in temperature
      lead to higher sample densification, even though densification represents a
      drawback for bone ingrowth. Cytotoxicity tests did not reveal any toxic effects
      of the starting and processed materials on surviving cell percentage. After an 8
      week healing period in rabbit tibias, the implants were retrieved, processed for
      nondecalcified histological evaluation, and then assessed by backscattered
      electron images (BSEI-SEM) and EDX. Bone growth into the microstructure was
      observed only in samples sintered at 1000 degrees C. Overall, a close relation
      between newly formed bone and all processed samples was observed.

PMID- 18335529
TI  - Retention and biodistribution of microspheres injected into ischemic myocardium.
AB  - Intramyocardial injection of therapeutic agents may enhance heart repair after
      infarction. Incomplete retention of intramyocardial injections has been reported,
      but modes of loss are undefined. We determined the fate of neutron-activated
      microspheres injected into acutely ischemic rat myocardium using saline, Pluronic
      F127, or Matrigel as vehicle. Twenty minutes after injection in saline, 63% +/-
      12% of 10-mum microspheres was retained in the heart. Similar retention was
      observed after 6 days. Injection site leakage accounted for 14% +/- 5% of the
      microspheres, whereas exit via coronary veins resulted in 11.2% +/- 9.5%
      collecting in the lungs. Microspheres distribution to other organs was minimal.
      Retention of 40-mum microspheres was similar to that observed with the 10-mum
      microspheres. Pluronic F127 and Matrigel reduced immediate leakage to 4% +/- 1%
      and 2% +/- 1%, respectively. Surprisingly, microsphere retention in the heart was
      not improved at 20 min using either gelling vehicle, suggesting that leakage
      occurs over a prolonged period. Thus, most injected particles are retained in the
      ischemic rat heart following direct injection, but significant fractions are lost
      from the injection site and through coronary veins. Gelling agents reduced short
      term leakage, but failed to enhance longer-term retention. Hydrogels with stiffer
      mechanical properties might enhance retention and reduce variability.

PMID- 18335530
TI  - Immunohistochemical identification of MMP-2 and MMP-9 in human dentin:
      correlative FEI-SEM/TEM analysis.
AB  - Matrix metalloproteinases (MMPs) are a family of peptidases trapped within
      mineralized dentin matrix and involved with degradation of the extracellular
      matrix components in hybrid layers and caries. Despite their identification
      through indirect evidences and biochemical assays, MMP-2 and -9 have not been
      localized within the human dentin extracellular organic matrix. Thus, this study
      aimed to assess the localization and distribution of MMP-2 and -9 in human dentin
      organic matrix by employing a correlative field emission in-lens-scanning
      electron microscopy (FEI-SEM) and transmission electron microscopy (TEM)
      immunohistochemical approach. Dentin specimens were submitted either to a
      preembedding or to a postembedding immunolabeling technique using primary
      monoclonal antibodies anti-MMP-2 and anti-MMP-9 and exposed to a secondary
      antibody conjugated with gold nanoparticles. MMP-2 and -9 labelings were
      identified in the demineralized dentin matrix as highly electron-dense gold
      particles dispersed on the collagen fibrils. Correlative FEI-SEM/TEM observations
      confirmed that MMP-2 and MMP-9 are endogenous components of the human dentin
      organic matrix and revealed the three-dimensional relationship between these
      proteinases and the collagen fibrils, showing that both antibodies yielded a
      similar labeling pattern. In conclusion, the results of the study contribute to
      reveal distinct distribution pattern of gelatinases and support the hypothesis
      that these enzymes are intrinsic constituents of the dentin organic matrix after
      decalcification.

PMID- 18335531
TI  - Effects of fabrication parameters on viscoelastic shear modulus of 2,3
      dialdehydecellulose membranes--potential scaffolds for vocal fold lamina propria
      tissue engineering.
AB  - Porous 2,3-dialdehydecellulose (2,3-DAC) membranes were investigated for use as a
      synthetic scaffold for engineering vocal fold-like tissues. Two criteria of this
      application are (i) the viscoelastic shear properties of the scaffold should be
      controllable in the range of vocal fold tissues and (ii) scaffolds should remain
      biomechanically stable to withstand vibrational stresses in a bioreactor. Porous
      2,3-DAC membranes were fabricated from methylolcellulose by water-induced
      cellulose regeneration, with or without sodium chloride leaching, followed by
      periodate oxidation. They were freeze-dried and ethylene oxide-sterilized.
      Different degrees of oxidation were obtained on reacting with sodium
      metaperiodate for different time points. Rheological studies were performed to
      investigate the effect of freeze-drying, porosity, degree of oxidation,
      sterilization, and incubation time on elastic and viscous shear moduli, G' and
      G'', respectively, for frequencies 0.01-10 Hz. Freeze drying increased G' and
      G'', while increased porosity and degree of oxidation reduced G' and G''.
      Sterilization had no effect on viscoelasticity. When incubated in Dulbecco's
      minimum essential medium at 37 degrees C, membranes with 6-7% and 19-20%
      oxidation disintegrated after 7 and 3 days, respectively, while membranes with 3
      4% oxidation showed little viscoelastic change over a period of 42 days. The
      upper frequency limit of rheologic measurement was a limitation of the study and
      should be addressed in future investigations.

PMID- 18335532
TI  - Metal-on-metal bearings in total hip arthroplasties: Influence of cobalt and
      chromium ions on bacterial growth and biofilm formation.
AB  - Metal-on-metal (MOM) bearings involving cobalt-chromium (Co-Cr) alloys in total
      hip arthroplasties are becoming more and more popular due to their low wear.
      Consequences of corrosion products of Co-Cr alloys are for the most part unclear,
      and the influence of cobalt and chromium ions on biofilm formation has never been
      studied. Therefore, the aim of this study was to evaluate how Co-Cr ions affect
      bacterial growth, biofilm formation, and architecture. A collection of clinically
      isolated and commercially available bacterial strains were exposed to Co-Cr
      concentrations as found in serum and above as found in adjacent tissue.
      Planktonic growth of bacteria was inhibited by concentrations of 200,000/93,000
      microg/L Co-Cr. Co-Cr concentrations up to 20/9.3 microg/L as reported to occur
      in serum revealed no consistent influence on biofilm formation, but higher
      concentrations of 200,000/93,000 microg/L significantly reduced Staphylococcus
      aureus and CNS biofilm formation. As indicated by confocal laser scanning
      microscopy, no dead bacteria were encountered in the biofilms, and the metal ion
      concentrations used must be classified as growth-inhibiting and not bactericidal.
      Long-term clinical data on infection rates for Co-Cr MOM-bearings are not yet
      available, but the current results suggest that Co-Cr ions may yield these
      prostheses less prone to biofilm formation and subsequent infection.

PMID- 18335533
TI  - Effects of gold coating on experimental implant fixation.
AB  - Insertions of orthopedic implants are traumatic procedures that trigger an
      inflammatory response. Macrophages have been shown to liberate gold ions from
      metallic gold. Gold ions are known to act in an antiinflammatory manner by
      inhibiting cellular NF-kappaB-DNA binding and suppressing I-kappa B-kinase
      activation. The present study investigated whether gilding implant surfaces
      augmented early implant osseointegration and implant fixation by its modulatory
      effect on the local inflammatory response. Ion release was traced by
      autometallographic silver enhancement. Gold-coated cylindrical porous coated
      Ti6Al4V implants were inserted press-fit in the proximal part of tibiae in nine
      canines and control implants without gold inserted contralateral. Observation
      time was 4 weeks. Biomechanical push-out tests showed that implants with gold
      coating had approximately 50% decrease in mechanical strength and stiffness.
      Histomorphometrical analyses showed gold-coated implants had a decrease in
      overall total bone-to-implant contact of 35%. Autometallographic analysis
      revealed few cells loaded with gold close to the gilded implant surface. The
      findings demonstrate that gilding of implants negatively affects mechanical
      strength and osseointegration because of a significant effect of the released
      gold ions on the local inflammatory process around the implant. The possibility
      that a partial metallic gold coating could prolong the period of satisfactory
      mechanical strength, however, cannot be excluded.

PMID- 18335534
TI  - Surface-initiated atom-transfer radical polymerization of 3-O-methacryloyl
      1,2:5,6-di- O-isopropylidene-alpha- D-glucofuranoside onto gold surface.
AB  - A sugar-containing polymer was grown on gold surface by surface-initiated atom
      transfer radical polymerization (SI-ATRP) of methacrylate monomer, 3-O
      methacryloyl-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranoside (MAIpGIc), using
      1,4,8,11-tetraaza-1,4,8,11-tetramethylcyclotetradecane (Me(4)Cyclam) as ligand, 2
      bromopropionyl moiety attached on the gold surface as initiator, and Copper(I)
      bromide as catalyst, respectively, in tetrahydrofuran (THF) medium. The resultant
      sugar film was characterized by polarized infrared external reflectance
      spectroscopy (PIERS), X-ray photoelectron spectroscopy (XPS), atomic force
      microscopy (AFM), field emission scanning electron microscopy (FE-SEM),
      ellipsometry, and contact angle goniometry. The IR peaks characteristics of
      poly(3-O-methacryloyl-alpha,beta-D-glucopyranoside) (PMAGlc), broad O--H stretch
      at approximately 3400 cm(-1), and C==O ester stretch at approximately 1748 cm(-1)
      observed in PIERS spectra demonstrate the formation of PMAGlc on the gold
      surface. The AFM and SEM images show the polymer growth away from the gold
      surface without visible domain boundaries, and it further confirms the formation
      of sugar coating. The method described in the article would be beneficial in many
      areas, such as pathogen detection and biosensors, considering the biological
      importance of carbohydrate polymers.

PMID- 18335535
TI  - The bone-derived collagen containing mineralized matrix for the loading of
      collagen-binding bone morphogenetic protein-2.
AB  - Bone tissue-derived biomaterials have often been applied for bone repair because
      of their similarity to human bone in structure and composition. When combined
      with growth factors, they could accelerate bone formation. Here, we explore a
      collagen containing mineralized bone-derived matrix (CCMBM) from bovine bone
      tissues, which not only maintains proper mechanical strength but also binds to
      the collagen-binding recombinant human collagen-binding bone morphogenetic
      protein-2 (CBD-BMP(2)). By analyzing its morphology and composition, we found
      that CCMBM was porous and mainly composed of calcium compounds. CCMBM could
      provide mechanical support for bone injury repair. It also showed good
      biocompatibility and proper degradation rate that would be helpful for bone
      regeneration. In addition, the intentionally preserved collagen allowed the
      specific binding of CBD-BMP(2) to CCMBM, and resulted in significantly increased
      osteogenesis in vivo. The results indicated that the combination of CCMBM with
      collagen-binding BMP(2) could be emerged into an effective medical device for
      bone repair.

PMID- 18335536
TI  - Histopathology of the three implanted degradable biopolymers in rabbit eye.
AB  - New straightforward applications of new biopolymers are needed in glaucoma
      surgery. The aim of this study was to compare biocompatibility of three
      biomaterials in rabbit eyes after deep sclerectomy; a collagen implant (AquaFlow)
      represented the "gold standard". A blend of 85:15 poly(L-lactide-co-glycolide)
      and 70:30 poly(L-lactide-co-1,3-trimethylene carbonate) copolymers in a molar
      ratio of 70:30 (Bio-1 = Inion GTR membrane) and poly(DL-lactide-co-glycolide with
      molar compositions of 50:50 (Bio-2) and 85:15 (Bio-3) were inserted into rabbits
      eyes. Bio-1, Bio-2 or Bio-3 caused very mild eye irritation or tissue response
      which was comparable to that of the collagen implant. The biodegradation time of
      Bio-1, Bio-2, and Bio-3 implants was over one year, 3 months and 6 months,
      respectively. Implant mapping by Fourier transform infrared (FTIR) microscopy
      revealed a heterogeneous distribution of degradation products throughout Bio-1,
      Bio-2, and Bio-3. All implants were surrounded by a very fine tissue capsule
      which was not visible after total degradation of the implants. The FTIR spectrum
      of tissue capsule around Bio-1 was almost identical to that around Bio-2 whereas
      significant differences were observed in the spectrum of the tissue capsule
      around Bio-3. Despite some differences in tissue response, all tested implants
      represent biologically acceptable materials for drainage devices in glaucoma
      surgery.

PMID- 18335537
TI  - Differential projections from the vestibular nuclei to the flocculus and uvula
      nodulus in pigeons (Columba livia).
AB  - The pigeon vestibulocerebellum is divided into two regions based on the responses
      of Purkinje cells to optic flow stimuli: the uvula-nodulus responds best to self
      translation, and the flocculus responds best to self-rotation. We used retrograde
      tracing to determine whether the flocculus and uvula-nodulus receive differential
      mossy fiber input from the vestibular and cerebellar nuclei. From retrograde
      injections into the both the flocculus and uvula-nodulus, numerous cells were
      found in the superior vestibular nucleus (VeS), the cerebellovestibular process
      (pcv), the descending vestibular nucleus (VeD), and the medial vestibular nucleus
      (VeM). Less labeling was found in the prepositus hypoglossi, the cerebellar
      nuclei, the dorsolateral vestibular nucleus, and the lateral vestibular nucleus,
      pars ventralis. In the VeS, the differential input to the flocculus and uvula
      nodulus was distinct: cells were localized to the medial and lateral regions,
      respectively. The same pattern was observed in the VeD, although there was
      considerable overlap. In the VeM, the majority of cells labeled from the
      flocculus were in rostral margins on the ipsilateral side, whereas labeling from
      uvula-nodulus injections was distributed bilaterally throughout the VeM. Finally,
      from injections in the flocculus but not the uvula-nodulus, moderate labeling was
      observed in a paramedian area, adjacent to the medial longitudinal fasciculus. In
      summary, there were clear differences with respect to the projections from the
      vestibular nuclei to functionally distinct parts of the vestibulocerebellum.
      Generally speaking, the mossy fibers to the flocculus and uvula-nodulus arise
      from regions of the vestibular nuclei that receive input from the semicircular
      canals and otolith organs, respectively.

PMID- 18335538
TI  - Cyclic AMP concentration and protein kinase A (PKA) gene expression at different
      developmental stages of the polychaete Hydroides elegans.
AB  - The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) showed
      inductive effect on larval settlement of the polychaete Hydroides elegans. It has
      been suggested that IBMX triggers larval settlement by elevating the cellular
      adenosine 3',5'-cyclic monophosphate (cAMP) level in this species. To test this
      hypothesis, we first examined cAMP-level changes in both the competent (CL) and
      attached larvae (AL) and then characterized the cAMP-dependent protein kinase in
      H. elegans, which is the major mediator of cAMP action. Tissue extracts of the
      larvae were assayed for cAMP by enzyme immunoassay; the results showed that IBMX
      increased cAMP production up to approximately two-folds in the CL. However, there
      was no significant difference in the cAMP concentration between the CL and AL
      that were not treated with IBMX. The catalytic subunit of protein kinase A gene
      from H. elegans (designated HePKAc) was cloned, and its expression in different
      developmental stages of H. elegans was examined using quantitative real-time
      polymerase chain reaction. The gene expression level in the pre-competent
      trochophore larvae was the lowest, increased in the CL, reached the highest in
      the larvae undergoing normal and IBMX-induced metamorphosis, and then decreased
      in the adult stage. In situ hybridization results showed that HePKAc expressed
      mainly around eye regions and along body fragments of the CL and AL. Our results
      indicated that the IBMX-induced cAMP changes and the cAMP-dependent protein
      kinase gene may mediate larval development and settlement of H. elegans.

PMID- 18335539
TI  - Bulbospinal neurons implicated in mesopontine-induced anesthesia are
      substantially collateralized.
AB  - Microinjection of pentobarbital or other gamma-aminobutyric acid type A receptor
      (GABA(A)-R) active anesthetics into a brainstem region in the rat that we have
      called the mesopontine tegmental anesthesia area (MPTA) induces a general
      anesthesia-like state that includes suppression of locomotor activity, loss of
      the righting reflex, atonia, antinociception, and apparent loss of consciousness.
      The suppression of muscle tone and of nocifensive spinal reflexes suggests a
      direct or indirect effect at the level of the spinal cord itself, an inference
      supported by anterograde tracing from the MPTA area. We have now used single and
      double retrograde tracing to characterize this bulbospinal pathway further. The
      MPTA contains the majority of all bulbospinal neurons present at mesopontine
      levels (65.8%). Many of these neurons, although not all, appear to have a highly
      collateralized projection pattern within the spinal cord. About 40% of the MPTA
      neurons that project to the lumbar spinal cord also have collaterals at cervical
      levels, and about 60% of those with projections to the ventral horn also have
      projections to the dorsal horn (at cervical levels). However, the large majority
      projects either ipsilaterally or contralaterally. Relatively few ( approximately
      13%) send collaterals to both sides of the spinal cord. The pattern of
      connectivity revealed appears to be consistent with a system designed primarily
      to modulate motor and sensory functions globally, over the entire neuraxis,
      rather than regionally or segmentally.

PMID- 18335540
TI  - Diversity in mammalian chiasmatic architecture: ipsilateral axons are deflected
      at glial arches in the prechiasmatic optic nerve of the eutherian Tupaia
      belangeri.
AB  - Permanent ipsilaterally projecting axons approach the chiasmatic midline in
      rodents but are confined to lateral parts of the optic chiasm in marsupials.
      Hence, principally different mechanisms were thought to underlie axon pathway
      choice in eutherian (placental) and marsupial mammals. First evidence of
      diversity in eutherian chiasmatic architecture came from studies in the newborn
      and adult tree shrew Tupaia belangeri (Jeffery et al. [1998] J. Comp. Neurol.
      390:183-193). Here, as in marsupials, ipsilaterally projecting axons do not
      approach the midline. The present study aims to clarify how the developing tree
      shrew chiasm is organized, how glial cells are arranged therein, and the extent
      to which the tree shrew chiasm is similar to that of marsupials or other
      eutherians. By using routinely stained serial sections as well as
      immunohistochemistry with antibodies against glial fibrillary acidic protein,
      vimentin, and medium-molecular-weight neurofilament protein, we investigated
      chiasm formation from embryonic day 18 (E18) to birth (E43). From E22 onward,
      ipsilaterally projecting axons diverged from contralaterally projecting axons in
      prechiasmatic parts of the optic nerve. They made sharp turns when arriving at
      glial arches found at the transition from the optic nerve to the chiasm. Thus,
      during the ingrowth period of axons, Tupaia belangeri and marsupials have
      specialized glial arrays in common, which probably help to deflect ipsilaterally
      projecting axons to lateral parts of the chiasm. Our observations provide new
      evidence of diversity in eutherian chiasmatic architecture and identify Tupaia
      belangeri as an appropriate animal model for studies on the mechanisms underlying
      axon guidance in the developing chiasm of higher primates.

PMID- 18335541
TI  - MBNL1 associates with YB-1 in cytoplasmic stress granules.
AB  - The muscleblind-like (MBNL) protein family is thought to be involved in the
      molecular mechanism of myotonic dystrophy (DM). Although it has been shown to
      have splicing activity, a broader function in cellular RNA metabolism has been
      implicated. In this study, we attempted to find the binding proteins of MBNL1 in
      order to elucidate its physiological function. First, we performed a GST pull
      down assay using GST-MBNL1-6xHis as bait. Several proteins were identified,
      including YB-1, a multifunctional DNA/RNA-binding protein, and DDX1, a DEAD box
      RNA helicase. MBNL1 formed an RNP complex with YB-1 and DDX1 in binding assays.
      YB-1 also showed a weak but significant effect on alpha-actinin splice site
      selection. Interestingly, in response to stress, MBNL1 moved to cytoplasmic
      stress granules, where it colocalized with YB-1, which was previously reported to
      be a component of stress granules. We found that DDX1 also colocalized with MBNL1
      at stress granules. These results provide new insight into the dynamics of MBNL1
      in response to stress, and they suggest a role for MBNL1 in mRNA metabolism in
      the cytoplasm.

PMID- 18335542
TI  - Retrograde Wallerian degeneration of cranial corticospinal tracts in cervical
      spinal cord injury patients using diffusion tensor imaging.
AB  - Diffusion tensor imaging (DTI) has the potential to reveal disruption of white
      matter microstructure in chronically injured spinal cords. We quantified
      fractional anisotropy (FA) and mean diffusivity (MD) to demonstrate retrograde
      Wallerian degeneration (WD) of cranial corticospinal tract (CST) in cervical
      spinal cord injury (SCI). Twenty-two patients with complete cervical SCI in the
      chronic stage were studied with DTI along with 13 healthy controls. Mean FA and
      MD values were computed for midbrain, pons, medulla, posterior limb of internal
      capsule, and corona radiata. Significant reduction in the mean FA and increase in
      MD was observed in the cranial CST in patients with SCI compared with controls,
      suggesting retrograde WD. Statistically significant inverse FA and MD changes
      were noted in corona radiata, indicating some restoration of spared white matter
      tracts. Temporal changes in the DTI metrics suggest progressing degeneration in
      different regions of CST. These spatiotemporal changes in DTI metrics suggest
      continued WD in injured fibers along with simultaneous reorganization of spared
      white matter fibers, which may contribute to changing neurological status in
      chronic SCI patients.

PMID- 18335543
TI  - Implications of antiinflammatory properties of the anticonvulsant drug
      levetiracetam in astrocytes.
AB  - There is accumulating evidence that epileptic activity is accompanied by
      inflammatory processes. In the present study, we evaluated the effect of
      levetiracetam (Keppra), an anticonvulsant drug with decisive antiepileptic
      features, with regard to its putative antiinflammatory potential. We previously
      established an in vitro cell culture model to mimic inflammatory conditions:
      Primary astrocytic cultures of newborn rats were cocultured with 30% (M30)
      microglial cells. Alternatively, cocultures containing 5% microglia (M5) were
      incubated with the proinflammatory mediator, the cytokine interleukin-1beta (IL
      1beta), and lipopolysaccharide (LPS), a potent bacterial activator of the immune
      system. For the M30 cocultures, we observed reduced expression of connexin 43
      (Cx43), the predominant gap junction protein. Impaired functional dye coupling
      and depolarized membrane resting potential (MRP) were monitored in M30 cocultures
      as well as in M5 cocultures treated with IL-1beta and LPS. We could show that the
      Cx43 expression, the coupling property, and the membrane resting potential on
      which we focused our inflammatory coculture model were normalized to
      noninflammatory level under treatment with levetiracetam (Keppra). Cumulatively,
      our results provide evidence for antiinflammatory properties of levetiracetam in
      seizure treatment.

PMID- 18335544
TI  - Activation of phenotypically distinct neuronal subpopulations in the anterior
      subdivision of the rat basolateral amygdala following acute and repeated stress.
AB  - The effects of acute and repeated stress on expression of the early immediate
      gene c-fos in the basolateral amygdala have previously been reported; however,
      characterization of which neuronal subpopulations are activated by these stimuli
      has not been investigated. This question is of considerable relevance, insofar as
      the basolateral amygdala houses a heterogeneous population of neurons, including
      those of gamma-aminobutyric acid (GABA)-ergic and glutamatergic phenotypes that
      may be subcategorized based on their expression of various calcium-binding
      proteins, including parvalbumin, calbindin, calretinin, and the calcium-sensitive
      enzyme calcium/calmodulin-dependent kinase II. Characterization of these
      subpopulations has revealed unique differences in their physiology, synaptology,
      and morphology, suggesting that each distinct phenotype may have profound effects
      on the local circuitry of the amygdala. Therefore, we examined the effects of
      acute and repeated restraint stress on expression of the immediate early gene c
      fos in neurons containing parvalbumin, calbindin, calretinin, or
      calcium/calmodulin-dependent kinase II in the basolateral amygdala. Double-label
      immunohistochemistry revealed that acute restraint stress activated a proportion
      of parvalbumin-, calbindin-, or calcium/calmodulin-dependent kinase II-positive
      neurons. Prior exposure to repeated restraint stress markedly attenuated acute
      stress mediated activation of these neuronal populations, although not equally.
      Expression of c-Fos protein was not detected in calretinin-positive neurons in
      any experimental group. These results demonstrate that distinct neuronal
      phenotypes in the basolateral amygdala are activated by acute restraint stress
      and that prior repeated restraint stress differentially affects this response.

PMID- 18335545
TI  - Identity of myelinated cutaneous sensory neurons projecting to nocireceptive
      laminae following nerve injury in adult mice.
AB  - It is widely thought that, after peripheral injury, some low-threshold
      mechanoreceptive (LTMR) afferents "sprout" into pain-specific laminae (I-II) of
      the dorsal horn and are responsible for chronic pain states such as mechanical
      allodynia. Although recent studies have questioned this hypothesis, they fail to
      account for a series of compelling results from single-fiber analyses showing
      extensive projections from large-diameter myelinated afferents into nocireceptive
      layers after nerve injury. Here we show that, in the thoracic spinal cord of
      naive adult mouse, all myelinated nociceptors gave rise to terminal projections
      throughout the superficial dorsal horn laminae (I-II). Most (70%) of these fibers
      had large-diameter axons with recurving flame-shaped central arbors that
      projected throughout the dorsal horn laminae I-V. This morphology was reminiscent
      of that attributed to sprouted LTMRs described in previous studies. After
      peripheral nerve axotomy, we found that LTMR afferents with narrow, uninflected
      somal action potentials did not sprout into superficial laminae of the dorsal
      horn. Only myelinated noiceptive afferents with broad, inflected somal action
      potentials were found to give rise to recurving collaterals and project into
      superficial "pain-specific" laminae after axotomy. We conclude that the
      previously undocumented central morphology of large, myelinated cutaneous
      nociceptors may very well account for the morphological findings previously
      thought to require sprouting of LTMRs.

PMID- 18335546
TI  - Crystal-like structure in urine sediment.

PMID- 18335547
TI  - Adenolipoma of the thyroid gland: report of a case with diagnosis by fine-needle
      aspiration cytology.
AB  - Adenolipomas are rare benign neoplasms composed of mature adipose tissue and
      thyroid follicles. The preoperative fine-needle aspiration cytology of such
      lesion has rarely been cited. Approximately 12 cases have been reported in the
      literature worldwide, diagnosed solely on histopathology. A 65-year-old woman
      presented with a 4-month history of a thyroid nodule. A FNA cytology specimen
      showed a few benign follicular cells with adipose tissue. Right lobectomy was
      performed and the specimen revealed a solid yellowish mass measuring 3 x 2.5 cm.
      Microscopic findings showed a solid tumor predominantly composed of mature
      adipose tissue intermixed with thyroid follicles. The pathological diagnosis was
      adenolipoma of the thyroid gland. The presence of adipose tissue is a common
      finding within the cytologic specimen, especially in obese individuals or with
      inadequate sampling. But suspicion may be possible if excess amounts of adipose
      tissue are present in the submitted sample.

PMID- 18335548
TI  - Disseminated subcutaneous nocardiosis caused by Nocardia farcinica diagnosed by
      FNA biopsy and 16S ribosomal gene sequencing.
AB  - Nocardia is an infrequent but significant cause of infections in the
      immunocompromised host. Clinical syndromes are varied and ranges from pulmonary,
      disseminated, cutaneous, and CNS involvement. Here we describe a case of
      disseminated subcutaneous nodules in a patient with multiple myeloma caused by
      Nocardia farcinica. The diagnosis was made by FNA biopsy which revealed gram
      positive filamentous bacilli in background of acute inflammation on smears. This
      was confirmed by 16S ribosomal gene sequencing. Prompt identification of N.
      farcinica is important because of its intrinsic resistance to broad spectrum
      cephalosporins and high risk of dissemination.

PMID- 18335549
TI  - Bronchial carcinoid tumor: cytologic features on ThinPrep and a diagnostic
      pitfall in bronchial brushings and washings.

PMID- 18335550
TI  - Cytologic features of meningiomas on crush preparations: a review.
AB  - Meningiomas are rarely subjected to aspiration, however, since they may occur
      outside the central nervous system, it is important to recognize their cytologic
      features. The goal of this study was to examine the cytologic features of
      meningiomas in crush preparations and cytologic imprints prepared at the time of
      frozen section. A total of 97 cases of meningiomas evaluated intraoperatively by
      frozen section with concomitant crush preparation and cytologic imprint were
      reviewed to assess their cytologic features. The cytologic features of
      meningiomas identified in our study are cohesive syncitial clusters of cells with
      ill-defined boundaries. The nuclei are oval and may be eccentrically placed,
      along with small central nucleoli. The cytologic features may not reflect the
      histologic subtype. The psammomatous variant can however be easily recognized in
      touch preps/imprints. The presence of nuclear anaplasia, macronucleoli, mitotic
      activity, and sheet-like growth may suggest an atypical meningioma. In
      conclusion, the cytologic features identified would be helpful in diagnosis of
      meningiomas, especially in unusual locations.

PMID- 18335551
TI  - Utility of thin-layer preparations in endometrial cytology: immunocytochemical
      expression of PTEN, beta-catenin and p53 for benign endometrial lesions.
AB  - This article focuses on the characteristic features of morphology and molecular
      biology of PTEN, beta-catenin, and p53 immunocytochemistry in normal endometrium
      (proliferative, secretory, and atrophic) and endometrial glandular and stromal
      breakdown (EGBD) using thin-layer specimens. During a 6-month period, 120
      endometrial samples were collected directly using the Uterobrush and a thin-layer
      specimen was prepared. Immunocytochemical expression of PTEN, beta-catenin, and
      p53 were investigated using 30 cases each of proliferative endometrium (PE),
      secretory endometrium (SE), atrophic endometrium (AE), and EGBD.PTEN expression
      of normal endometrial glandular epithelial cells changes with the hormonal
      status; PE produce very high expression, SE creates attenuation or disappearance
      of PTEN expression and AE diminished more in comparison with SE. PTEN expression
      of EGBD showed a tendency towards attenuation compared with PE, but showed high
      expression in comparison with SE and AE. As for the immunoreactivity of beta
      catenin, in all phases (PE, SE, AE, and EGBD), it was observed in the cytoplasm
      of glandular epithelial cells, but not nuclei, and showed strong membranous
      staining. As for the p53 immunoreactivity, p53 positivity was not observed in the
      glandular epithelial cells in all phases (PE, SE, AE, and EGBD) with the
      exception of some metaplastic cells. The presence of p53 immunoreactivity of a
      weak, low ratio in metaplastic cells was unexpected. In the current study, the
      expression manner of PTEN, beta-catenin, and p53 immunocytochemistry was observed
      in the normal endometrium (PE, SE, and AE) and EGBD.

PMID- 18335552
TI  - Fine-needle aspiration cytodiagnosis of endometriosis in cesarean section scar
      and rectus sheath mass lesions -- a study of seven cases.
AB  - The diagnosis of endometriosis is usually established by a biopsy. Since
      endometriotic lesions can present as a mass lesion, it seems feasible to
      investigate them by the noninvasive method of fine-needle aspiration cytology
      (FNAC). In this study, seven cases (5 from a cesarean scar and 2 from rectus
      sheath) are presented in which FNAC was indicative of endometriosis. The aspirate
      was obtained using a disposable 10 ml syringe and 22 gauge needle. The material
      was collected as syringe and needle washings in a cytology container in which 30%
      ethyl alcohol was present. From half of this material, filter preparations were
      made on size 3 mum filters and stained by Papanicolaou method, while the
      remaining aspirate was spun and a cell block was made from the sediment and
      sections cut and stained with hematoxylin-eosin stain. In all cases the cytologic
      preparations showed tubular structures indicative of endometrial tissue and
      stromal cells indicative of endometriosis. This was further confirmed on
      examination of cell blocks, which showed histologic features of endometriosis
      characterized by endometrial glands separated by endometrial stroma and rare
      siderophages. The seven cases described are interesting, since the
      cytohistological finding in FNAC sample and cell block not only were indicative
      of the diagnosis of endometriosis, but also obviated the need for an invasive
      surgical procedure.

PMID- 18335553
TI  - Cytologic features of endocervical glandular lesions: comparison of SurePath,
      ThinPrep, and conventional smear specimen preparations.
AB  - The cytologic features of endocervical neoplasia have been well-described for
      conventional and ThinPrep, but not for SurePath, methods. This study is designed
      to ascertain if cytological features are similar in SurePath specimens.
      Conventional, ThinPrep and SurePath specimens with either endocervical
      adenocarcinoma in situ or invasive endocervical adenocarcinoma were evaluated for
      architectural and cytological features previously described for endocervical
      neoplasia. A generalized linear model was used to assess the differences of
      ordinal multinomial data. Of 18 evaluated, the only features showing statistical
      differences were architectural: large groups of cells and single cells were more
      frequent in SurePath preparations and conventional smears. Feathering was more
      frequently noted in conventional smears. Individual cytological features were
      identical across all groups. Mitoses and apoptotic debris were seen with equal
      frequency in all preparations. The architectural and cytologic features of
      endocervical glandular neoplasia in liquid-based specimens show only subtle
      architectural differences when compared with conventional smears. Keeping these
      differences in mind, virtually the same criteria can be used to identify
      endocervical glandular lesions in all three specimen types.

PMID- 18335554
TI  - Diagnosing mycobacterial lymphadenitis in children using fine needle aspiration
      biopsy: cytomorphology, ZN staining and autofluorescence -- making more of less.
AB  - Although the incidence of TB has stabilized or declined in most world regions, it
      is increasing in Africa, Southeast Asia, and the Eastern Mediterranean, fuelled
      by the HIV pandemic. More than 4,000 people died daily from TB-related illnesses
      in 2005. TB is a major cause of childhood morbidity and mortality in these
      developing countries, and there is an urgent need for rapid and definitive
      modalities for mycobacterial diagnosis in children. This prospective study in
      Tygerberg Hospital, Cape Town, South Africa, evaluates the ability of fine needle
      aspiration biopsy (FNAB) to diagnose mycobacterial lymphadenitis in children,
      using cytomorphology, autofluorescence on Papanicolaou stained smears, Ziehl
      Nielsen (ZN) staining and/or culture. FNABs were performed on 200 children, and
      25 (12.5%) aspirates were inadequate. Cultures were positive in 79/175 (45%);
      Mycobacterium tuberculosis was identified in 61 and Mycobacterium bovis BCG in 18
      cases. Using culture as the gold standard, the concordance of the different
      techniques was as follows: cytomorphology 70%, ZN staining 73%, and
      autofluorescence 68%. Using an alternative gold standard (culture positive and/or
      suggestive cytomorphology plus positive autofluorescence or ZN smear), the "true"
      diagnostic performance of the various techniques was as follows: cytomorphology
      sensitivity 78%, specificity 91%, positive predictive value (PPV) 93%, ZN
      staining - sensitivity 62%%, specificity 97%, PPV 97%; autofluorescence
      sensitivity 67%, specificity 97%, PPV 97%; and culture-sensitivity 75%,
      specificity 100%, and PPV 100%. FNAB was shown to provide a rapid and definitive
      diagnosis in the majority of cases of suspected tuberculous lymphadenitis in
      children, based on cytomorphology and identification of the organism.

PMID- 18335555
TI  - Plasmablastic lymphoma involving breast: a case diagnosed by fine-needle
      aspiration and core needle biopsy.
AB  - Plasmablastic lymphoma (PBL) is a rare lymphoma originating from B-cells with
      terminal differentiation. Most common anatomic site involved by PBL is the oral
      cavity. Involvement of other body sites has only rarely been reported. Herein, we
      report a rare case of EBV-negative PBL involving the breast of an HIV positive 47
      year-old woman. The patient presented with decreased vision and photophobia.
      During physical examination, she was found to have bilateral breast masses and
      multiple lymphadenopathy. Fine-needle aspiration of one of the breast masses
      showed large malignant cells with plasmacytoid features. Immunohistochemical
      studies performed on the core biopsy showed that the tumor cells were positive
      for common leukocyte antigen CD45 and plasma cell marker CD138, but negative for
      the pan-B cell markers CD20 and CD79a. Molecular genetic studies showed clonal
      rearrangement of the immunoglobulin kappa light chain gene. This is the first
      case of PBL involving the breast reported in English cytological literature.

PMID- 18335556
TI  - Intrapancreatic accessory spleen: mimic of pancreatic endocrine tumor diagnosed
      by endoscopic ultrasound-guided fine-needle aspiration biopsy.
AB  - Intrapancreatic accessory spleen forms a well-defined nodule within the tail of
      the pancreas and is commonly mistaken by imaging studies as a neuroendocrine
      tumor. We report three cases of intrapancreatic accessory spleen diagnosed by
      endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) biopsy. Imaging
      studies showed well-circumscribed nodules in the tail of the pancreas. Two
      lesions were clinically suspicious for pancreatic neuroendocrine tumors and one
      appeared to be a cyst. EUS-guided FNA revealed predominantly small lymphocytes
      with a subset of histiocytes, conspicuous eosinophils, and plasma cells. There
      was also characteristic CD8 positive immunostaining of endothelial cells in cell
      block sections. We report the first series of accessory spleen in the pancreas
      diagnosed by EUS-guided FNA with the aid of CD8 immunostaining of splenic sinus
      endothelial cells.

PMID- 18335557
TI  - How accurate is cytological diagnosis of cervical glandular lesions?
AB  - Gynecological cytology has some inaccurate morphological categorization and poor
      interobserver reproducibility especially for glandular lesions. Liquid-based
      cytology (LBC) preparations are presumed to reduce artifacts that interfere in
      diagnosis performance, but its value to correctly identify glandular alterations
      has not been sufficiently reported. The objective of this study was to compare
      the diagnostic performance and interobserver agreement of LBC and conventional
      Pap smear to identify histologically confirmed glandular lesions according to
      five cytologists. Sensitivity ranged from 55.8 to 73.1% and 32.7 to 48.1% for Pap
      smear and LBC, respectively. Specificity ranged from 66.1 to 87.1% and 69.4 to
      94.4%, respectively. In general, agreement between pairs of cytologists was poor
      with kappa-values around 0.45. In conclusion, relying entirely on cervical
      cytology to rule out glandular lesions may be risky. The use of HPV DNA test
      alone or combined to screening glandular lesions may contribute to minimize the
      limitations of both conventional and LBC preparations to diagnose glandular
      abnormalities.

PMID- 18335558
TI  - Back to basics: validation of automated as compared to manual slide staining in
      the cytopathology laboratory.
AB  - Regulatory agencies on laboratory accreditation require that a laboratory
      validate and document an instrument's functionality in its own specific
      environment, including the capability of the instrument to replace existing
      processes. Instruments without manufacturer-provided validation protocols must
      still undergo validation with documentation of the specific method used. This
      study was performed to validate the Sakura Tissue-Tek DRS 2,000 automated slide
      stainer.

PMID- 18335559
TI  - Immunocytochemical typing of primary tumors on fine-needle aspiration cytologies
      of lymph nodes.
AB  - The aim of this study was to analyze the role of immunocytochemistry as an
      ancillary method on routine FNACs of enlarged lymph nodes, using different
      markers. In a validating cohort study all patients had confirmatory histological
      and/or clinical follow-up. 10 FNACs were analyzed for the differentiation of Non
      Hodgkin Lymphoma (NHL) from metastatic carcinoma (MC), 30 cases to identify the
      sites of metastatic unknown primary tumors and 16 cases were checked to confirm
      clinical suspicion of a specific MC. Accuracy to differentiate NHL from MC was
      100%, 92.3% to identify a primary tumor site of MC, and 100% to confirm a
      clinical suspicion of a specific MC. In 7 cases, the site of the primary tumor
      remained clinically unknown. Application of immunocytochemical markers on the
      same slide used for microscopic diagnosis is a useful tool in the routine
      assessment of FNACs of lymph nodes.

PMID- 18335560
TI  - Parathyroid hormone assay in fine-needle aspirate is useful in differentiating
      inadvertently sampled parathyroid tissue from thyroid lesions.
AB  - To assess the utility of chemical analysis for parathyroid hormone in the rinse
      (PTH-r) obtained via fine-needle aspiration (FNA) in the setting of inadvertently
      sampled parathyroid tissue or lesions (PTL) during "thyroid" or "neck" FNA, the
      authors review their experience at a large, tertiary care academic medical
      center. All cases of inadvertent sampling of PTL during "thyroid" or "neck" FNA
      were identified by computer search. The cytologic and histologic material was
      reviewed and pertinent clinical data including patient demographics, serum
      calcium, intact serum PTH (PTH-s), and intact PTH-r was recorded. The cytologic
      interpretations and histologic diagnoses were also recorded. Of 3,521 cases of
      total thyroid and neck FNA during the study 21 (0.59%) cases of histologically
      confirmed sampling of PTL were identified. In all 10 cases with PTH-r the level
      was markedly elevated (range 248-240,075 pg/mL) and in every case PTH-r/PTH-s was
      elevated (range 3.67-458.3). In all 10 cases with PTH-r the cytologic diagnosis
      was PTL or included PTL in the differential. In 4/11 cases without PTL-r
      diagnoses of thyroid neoplasm or suspicious for thyroid neoplasm were rendered,
      each resulting in thyroidectomy. PTH-r has utility in differentiating PTL from
      thyroid lesions in the setting of inadvertent sampling of PTL during thyroid or
      neck FNA. Cellular specimens with features not typical for thyroid lesions should
      be triaged for PTL-r. Routine use of PTH-r will result in appropriate triage of
      patients to less aggressive excisional biopsies rather than unnecessary
      thyroidectomy.

PMID- 18335561
TI  - Giant-cell containing neoplasms of the pancreas: an aspiration cytology study.
AB  - Giant-cell containing neoplasms of the pancreas are rare with few reports
      documenting their cytologic appearance. Giant-cell containing neoplasms of the
      pancreas have been divided into two subtypes corresponding to the osteoclastic
      giant-cell tumor of the pancreas and the pleomorphic giant-cell carcinoma of the
      pancreas. Despite the better prognosis reported in some series for osteoclastic
      giant-cell tumors, the most recent edition of the World Health Organization
      classification lumps the two entities into a single category designated as
      undifferentiated carcinoma with osteoclast-like giant cells. Smears obtained from
      osteoclastic giant-cell tumors show numerous giant-cells with clustered
      overlapping, bland appearing nuclei containing prominent nucleoli consistent with
      an osteoclast-type multinucleated giant-cell. These neoplasms contain a second
      population of mononuclear cells showing more marked nuclear atypia. Pleomorphic
      giant-cell carcinomas are characterized by anaplastic giant-cells displaying
      marked nuclear pleomorphism. The mononuclear component is also pleomorphic with
      markedly atypical epithelioid and spindle shaped cells. In three reported cases,
      a tumor contained a mixture of the two cell patterns. Thus, undifferentiated
      carcinoma with osteoclast-like giant cells and pleomorphic giant cell carcinoma
      may represent a morphologic spectrum with pure osteoclast-like giant-cell tumors
      at one end and pleomorphic giant-cell carcinoma at the other. Fine-needle
      aspiration specimens from pure osteoclast-like giant-cell tumors will contain a
      population of bland multinucleated osteoclastic-like giant-cells that differ
      markedly from the anaplastic giant-cells of pleomorphic giant-cell carcinoma. The
      difference in the appearance of the giant-cells aids in distinction of the two
      neoplasms. When in pure form, the two neoplasms may follow different clinical
      courses.

PMID- 18335562
TI  - Nuclear factor I gene expression in the developing forebrain.
AB  - Three members of the Nuclear Factor I (Nfi) gene family of transcription factors;
      Nfia, Nfib, and Nfix are highly expressed in the developing mouse brain. Nfia and
      Nfib knockout mice display profound defects in the development of midline glial
      populations and the development of forebrain commissures (das Neves et al. [1999]
      Proc Natl Acad Sci U S A 96:11946-11951; Shu et al. [2003] J Neurosci 23:203-212;
      Steele-Perkins et al. [2005] Mol Cell Biol 25:685-698). These findings suggest
      that Nfi genes may regulate the substrate over which the commissural axons grow
      to reach targets in the contralateral hemisphere. However, these genes are also
      expressed in the cerebral cortex and, thus, it is important to assess whether
      this expression correlates with a cell-autonomous role in cortical development.
      Here we detail the protein expression of NFIA and NFIB during embryonic and
      postnatal mouse forebrain development. We find that both NFIA and NFIB are
      expressed in the deep cortical layers and subplate prenatally and display dynamic
      expression patterns postnatally. Both genes are also highly expressed in the
      developing hippocampus and in the diencephalon. We also find that principally
      neither NFIA nor NFIB are expressed in callosally projecting neurons postnatally,
      emphasizing the role for midline glial cell populations in commissure formation.
      However, a large proportion of laterally projecting neurons express both NFIA and
      NFIB, indicating a possible cell-autonomous role for these transcription factors
      in corticospinal neuron development. Collectively, these data suggest that, in
      addition to regulating the formation of axon guidance substrates, these genes
      also have cell-autonomous roles in cortical development.

PMID- 18335563
TI  - Morphology and physiology of vibratory interneurons in the thoracic ganglia of
      the southern green stinkbug Nezara viridula (L.).
AB  - The central processing mechanisms of vibratory signals in small plant-dwelling
      insects that rely primarily on substrate-borne vibratory communication are still
      largely unknown. To elucidate the neural mechanisms involved in vibratory
      signaling, the vibration-sensitive interneurons in thoracic ganglia of the
      southern green stinkbug, Nezara viridula, were investigated
      electrophysiologically by single-cell recordings and staining. Ten types of
      interneurons were described and divided into four categories, based on their
      gross morphology. The cell body of the L-shaped CG-AC neurons is located in the
      metathoracic neuromere of the central ganglion, and the axon ascends
      contralaterally. This group comprises five types of neurons differing in their
      fine structure and functional properties. CG-AB neurons are dorsal unpaired
      median (DUM) neurons with cell bodies in the mesothoracic neuromere of the
      central ganglion and two axons that ascend bilaterally into the prothoracic
      ganglion. Group CG-L includes three types of local neurons limited to the central
      ganglion. With ipsilateral dendritic arborizations and contralateral axonal
      branching, their gross morphology is similar to that of cricket omega cells.
      Interneuron PTG-DC, with the cell body in the prothoracic ganglion (PTG) and a
      contralaterally descending axon, conveys information received by the sensory
      organs of the front contralateral leg to the neuropil regions of the ipsilateral
      middle and hind legs. Based on their frequency tuning and acceleration
      sensitivity, the vibratory interneurons fall into two groups: the low-frequency
      units are tuned to 50 Hz and the middle frequency units to 200 Hz, with their
      acceleration thresholds at 10(-1) m/s(2) and 5 x 10(-3) m/s(2), respectively.
      Their function is discussed with relevance to the vibratory communication of N.
      viridula.

PMID- 18335564
TI  - Lethal vascular leak syndrome after denileukin diftitox administration to a
      patient with cutaneous gamma/delta T-cell lymphoma and occult cirrhosis.
AB  - Denileukin diftitox (Ontak) is an immunotoxin used in the treatment of cutaneous
      T-cell lymphomas. Vascular leak syndrome is a known complication of this therapy,
      although the syndrome is most often self-limited. We report the case of a patient
      with cutaneous gamma/delta (gammadelta) T-cell lymphoma and previous undiagnosed
      liver disease treated with denileukin diftitox. Just 4 days after initiating drug
      therapy, the patient developed profound vascular leak syndrome characterized by a
      rapid fall in his previously normal serum albumin to levels below the limit of
      detection. The patient then quickly deteriorated into rhabdomyolysis and eventual
      death. To our knowledge, this is the first report of a death directly related to
      denileukin diftitox therapy. The purpose of this case is to increase awareness
      and improve management of patients who are treated with denileukin diftitox with
      resulting vascular leak syndrome leading to hypoalbuminemia.

PMID- 18335565
TI  - Extracorporeal photopheresis: Lighting the way to immunomodulation.
AB  - Photopheresis, initially established as an effective treatment of cutaneous T
      cell lymphoma, has in recent years also been used to treat chronic graft vs. host
      disease, heart transplant rejection, and several other conditions requiring
      immunosuppression. Despite reported beneficial results of this procedure in
      treatment of various conditions, randomized controlled clinical trials are
      lacking for the majority of suggested indications. Furthermore, the mechanisms of
      action of this procedure are still unclear. Deeper understanding of the molecular
      basis of photopheresis-based immunomodulation will allow better selection of
      patients to be treated and will facilitate development of novel, minimally toxic
      immunomodulatory treatments.

PMID- 18335566
TI  - The use of hierarchical models for estimating relative risks of individual
      genetic variants: an application to a study of melanoma.
AB  - For major genes known to influence the risk of cancer, an important task is to
      determine the risks conferred by individual variants, so that one can
      appropriately counsel carriers of these mutations. This is a challenging task,
      since new mutations are continually being identified, and there is typically
      relatively little empirical evidence available about each individual mutation.
      Hierarchical modeling offers a natural strategy to leverage the collective
      evidence from these rare variants with sparse data. This can be accomplished when
      there are available higher-level covariates that characterize the variants in
      terms of attributes that could distinguish their association with disease. In
      this article, we explore the use of hierarchical modeling for this purpose using
      data from a large population-based study of the risks of melanoma conferred by
      variants in the CDKN2A gene. We employ both a pseudo-likelihood approach and a
      Bayesian approach using Gibbs sampling. The results indicate that relative risk
      estimates tend to be primarily influenced by the individual case-control
      frequencies when several cases and/or controls are observed with the variant
      under study, but that relative risk estimates for variants with very sparse data
      are more influenced by the higher-level covariate values, as one would expect.
      The analysis offers encouragement that we can draw strength from the aggregating
      power of hierarchical models to provide guidance to medical geneticists when they
      offer counseling to patients with rare or even hitherto unobserved variants.
      However, further research is needed to validate the application of asymptotic
      methods to such sparse data.

PMID- 18335568
TI  - On effect-measure modification: Relationships among changes in the relative risk,
      odds ratio, and risk difference.
AB  - It is well known that the presence or absence of effect-measure modification
      depends upon the chosen measure. What is perhaps more disconcerting is that a
      positive change in one measure may be accompanied by a negative change in
      another. Therefore, research demonstrating that an effect is 'stronger' in one
      population when compared with another, but based on only one measure, for
      example, the odds ratio, may be difficult to interpret for researchers interested
      in another measure. The present article investigates relationships among changes
      in the relative risk, odds ratio, and risk difference from one stratum to
      another. Monte Carlo integration shows that the three measures change in the same
      direction for 78 or 89 per cent of the volume of the geometric space defined by
      the four underlying proportions, depending on whether the strata are presumed to
      share the same direction of effect or not. Analytic results are presented
      concerning necessary and sufficient conditions for the measures to change in
      opposite directions. In general, the conditions are seen to be quite complicated,
      though they do give way to some interesting results. For example, when exposure
      increases risk but all risks are less than 0.5, it is impossible for the relative
      risk and risk difference to change in the same direction but opposite to that of
      the odds ratio. Both data-analytic and hypothetical examples are presented to
      demonstrate circumstances under which the measures change in opposite directions.

PMID- 18335569
TI  - Statistical methods in HIV/AIDS.

PMID- 18335571
TI  - Current awareness in prenatal diagnosis.

PMID- 18335570
TI  - [Papillomaviruses, at the time of vaccination].

PMID- 18335572
TI  - Floods hamper health-care delivery in southern Africa.

PMID- 18335573
TI  - New York moves to tackle shortage of primary-care doctors.

PMID- 18335574
TI  - AJO History of Ophthalmology series. Glaucoma in ophthalmologists.

PMID- 18335575
TI  - Abstracts of the Third Annual Academic Surgical Congress of the Association for
      Academic Surgery and the Society of University Surgeons. February 13-15, 2008.
      Huntington Beach, California, USA.

PMID- 18335576
TI  - MAM 2008. Abstracts of the Molecular Approaches to Malaria Conference. February 3
      7, 2008. Lorne, Victoria, Australia.

PMID- 18335577
TI  - Journal of Law and Medicine. Consolidated Index to Volumes 1-14. 1993-2007.

PMID- 18335578
TI  - Abstracts of the 23rd Congress of the European Committee for Treatment and
      Research in Multiple Sclerosis and the 12th Annual Conference of Rehabilitation
      in Multiple Sclerosis. October 11-14, 2007. Prague, Czech Republic.

PMID- 18335579
TI  - Inhibition of glucagon-signaling and downstream actions by interleukin 1beta and
      tumor necrosis factor alpha in cultured primary rat hepatocytes.
AB  - In cultured rat hepatocytes, glucagon increased the phosphoenolpyruvate
      carboxykinase (PCK1) mRNA by increasing cellular cAMP concentrations. The
      proinflammatory cytokines rhIL1beta and rhTNF alpha impaired the increase both in
      cAMP and PCK1 mRNA. Glucose formation from glycogen stimulated by glucagon was
      also attenuated by the cytokines, very likely due to the attenuation of the cAMP
      increase. Treatment of hepatocytes with the phosphodiesterase inhibitor IBMX or
      the inhibitory G-protein (G i) inactivating compound pertussis toxin did not
      abolish the inhibition of the glucagon-stimulated increase in cAMP by the
      cytokines indicating that phosphodiesterase and G i were not involved. The
      activation of adenylate cyclase by forskolin enhanced cAMP and PCK1 mRNA. Again,
      rhIL1beta and rhTNF alpha attenuated the increase in PCK1 mRNA, however, not that
      in cAMP. The stimulation of PCK1 mRNA increase with the nonhydrolyzable cAMP
      analogue CPT-cAMP was inhibited by rhIL1beta and rhTNF alpha indicating
      interference independent of changes in cAMP levels. It is concluded that
      rhIL1beta and rhTNF alpha inhibited glucagon-stimulated signal transduction at
      the site of cAMP formation. In addition, glucagon-stimulated PCK1 mRNA was
      attenuated independent of cAMP formation very likely on the transcriptional
      and/or post-transcriptional level.

PMID- 18335580
TI  - Effects of continuous low-carbohydrate diet after long-term exercise on GLUT-4
      protein content in rat skeletal muscle.
AB  - Stimulation of AMPK and decreased glycogen levels in skeletal muscle have a deep
      involvement in enhanced insulin action and GLUT-4 protein content after exercise
      training. The present study examined the chronic effects of a continuous low
      carbohydrate diet after long-term exercise on GLUT-4 protein content, glycogen
      content, AMPK, and insulin signaling in skeletal muscle. Rats were divided
      randomly into four groups: normal chow diet sedentary (N-Sed), low carbohydrate
      diet sedentary (L-Sed), normal chow diet exercise (N-Ex), and low carbohydrate
      diet exercise (L-Ex) groups. Rats in the exercise groups (N-Ex and L-Ex) were
      exercised by swimming for 6 hours/day in two 3-hour bouts separated by 45 minutes
      of rest. The 10-day exercise training resulted in a significant increase in the
      GLUT-4 protein content (p<0.01). Additionally, the GLUT-4 protein content in L-Ex
      rats was increased by 29% above that in N-Ex rats (p<0.01). Finally, the glycogen
      content in skeletal muscle of L-Ex rats was decreased compared with that of N-Ex
      rats. Taken together, we suggest that the maintenance of glycogen depletion after
      exercise by continuous low carbohydrate diet results in the increment of the GLUT
      4 protein content in skeletal muscle.

PMID- 18335581
TI  - Season of birth and chess expertise.
AB  - The origin of talent and expertise is currently the subject of intense debate,
      with explanations ranging from purely biological to purely environmental. This
      report shows that the population of expert chess players in the northern
      hemisphere shows a seasonal pattern, with an excess of births in late winter and
      early spring. This effect remains when taking into account the distribution of
      births in the population at large, using statistics from the European Union
      member countries. A similar pattern has been found with schizophrenia, and the
      possible link between these two phenomena is discussed.

PMID- 18335582
TI  - Kinetic properties of Ca2+/calmodulin-dependent phosphodiesterase isoforms
      dictate intracellular cAMP dynamics in response to elevation of cytosolic Ca2+.
AB  - Multiply regulated adenylyl cyclases (AC) and phosphodiesterases (PDE) can yield
      complex intracellular cAMP signals. Ca2+-sensitive ACs have received far greater
      attention than the Ca2+/calmodulin-dependent PDE (PDE1) family in governing
      intracellular cAMP dynamics in response to changes in the cytosolic Ca2+
      concentration ([Ca2+]i). Here, we have stably expressed two isoforms of PDE1,
      PDE1A2 and PDE1C4, in HEK-293 cells to determine whether they exert different
      impacts on cellular cAMP. Fractionation and imaging showed that both PDEs
      occurred mainly in the cytosol. However, PDE1A2 and PDE1C4 differed considerably
      in their ability to hydrolyze cAMP and in their susceptibility to inhibition by
      the non-selective PDE inhibitor, IBMX and the PDE1-selective inhibitor, MMX.
      PDE1A2 had an approximately 30-fold greater Km for cAMP than PDE1C4 and yet was
      more susceptible to inhibition by IBMX and MMX than was PDE1C4. These differences
      were mirrored in intact cells when thapsigargin-induced capacitative Ca2+ entry
      (CCE) activated the PDEs. Mirroring their kinetic properties, PDE1C4 was active
      at near basal cAMP levels, whereas PDE1A2 required agonist-triggered levels of
      cAMP, produced in response to stimulation of ACs. The effectiveness of IBMX and
      MMX to inhibit PDE1A2 and PDE1C4 in functional studies was inversely related to
      their respective affinities for cAMP. To assess the impact of the two isoforms on
      cAMP dynamics, real-time cAMP measurements were performed in single cells
      expressing the two PDE isoforms and a fluorescent Epac-1 cAMP biosensor, in
      response to CCE. These measurements showed that prostaglandin E1-mediated cAMP
      production was markedly attenuated in PDE1C4-expressing cells upon induction of
      CCE and cAMP hydrolysis occurred at a faster rate than in cells expressing PDE1A2
      under similar conditions. These results prove that the kinetic properties of PDE
      isoforms play a major role in determining intracellular cAMP signals in response
      to physiological elevation of [Ca2+]i and thereby provide a rationale for the
      utility of diverse PDE1 species.

PMID- 18335583
TI  - Malignant tumors of the maxilla: virtual planning and real-time rehabilitation
      with custom-made R-zygoma fixtures and carbon-graphite fiber-reinforced polymer
      prosthesis.
AB  - BACKGROUND: Oral cancer is a mutilating disease. Because of the expanding
      application of computer technology in medicine, new methods are constantly
      evolving. This project leads into a new technology in maxillofacial
      reconstructive therapy using a redesigned zygoma fixture. PURPOSE: Previous
      development experiences showed that the procedure was time-consuming and painful
      for the patients. Frequent episodes of sedation or general anesthetics were
      required and the rehabilitation is costly. The aim of our new treatment goal was
      to allow the patients to wake up after tumor surgery with a functional
      rehabilitation in place. MATERIALS AND METHODS: Stereolithographic models were
      introduced to produce a model from the three-dimensional computed tomography
      (CT). A guide with the proposed resection was fabricated, and the real-time
      maxillectomy was performed. From the postoperative CT, a second
      stereolithographic model was manufactured and in addition, a stent for the
      optimal position of the implants. Customized zygoma implants were installed (R
      zygoma, Integration AB, Goteborg, Sweden). A fixed construction was fabricated by
      using a new material based on poly(methylacrylate) reinforced with
      carbon/graphite fibers and attached to the implants. On the same master cast, a
      separate obturator was fabricated in permanent soft silicon. RESULTS: The result
      of this project showed that it was possible to create a virtual plan
      preoperatively to apply during surgery in order for the patient to wake up
      functionally rehabilitated. CONCLUSION: From a quality-of-life perspective, it is
      an advantage to be rehabilitated fast. By using new computer technology, pain and
      discomfort are less and the total rehabilitation is faster, which in turn reduces
      days in hospital and thereby total costs.

PMID- 18335584
TI  - Myeloperoxidase as a measure of polymorphonuclear leukocyte response in
      inflammatory status around immediately and delayed loaded dental implants: a
      randomized controlled clinical trial.
AB  - BACKGROUND: As well as gingival crevicular fluid (GCF), peri-implant sulcus fluid
      (PISF) may have a potential diagnostic value for the early identification of
      metabolic and destructive processes. PURPOSE: The aim of this study was to
      analyze the potential impact of inflammation and loading on PISF myeloperoxidase
      (MPO) levels, in comparison with GCF. MATERIALS AND METHODS: A total of 220
      sites, dental implant (immediately [IL] or delayed loaded [DL]), and natural
      tooth, either healthy/noninflamed or gingivitis/inflamed, were classified.
      Clinical parameters were recorded, and GCF/PISF samples were obtained. GCF/PISF
      MPO levels were spectrophotometrically determined. RESULTS: Clinical parameters
      demonstrated increases with the presence of gingival/peri-implant inflammation.
      Total MPO levels were higher at inflamed tooth and implant sites compared to
      noninflamed/healthy sites (p < .05). Although they did not reach a significance
      level, inflamed IL sites had higher total MPO levels than inflamed DL sites (p =
      .401). Gingival index and total MPO levels exhibited significant correlations (p
      < .05). CONCLUSION: Using implants and natural teeth in the same study design,
      the findings of the present study support the close relationship between MPO
      production and inflammation, and may speculate a potential for loading of dental
      implants, contributing to the MPO content of PISF.

PMID- 18335585
TI  - Molecular targets and cancer therapeutics. 19th annual AACR-NCI-EORTC conference
      October 22-26, 2007, San Francisco, California, USA.

PMID- 18335586
TI  - Eurofile. Private-public drive to cut delays in drug development.

PMID- 18335587
TI  - Novel trial designs for novel agents. Interview by Helen Saul.

PMID- 18335588
TI  - [Classification on ingional hernias].

PMID- 18335589
TI  - [System and regional antioxidan therapy by complicated diabetic foot].

PMID- 18335590
TI  - [Surgical treatment of giant aneurysm of internal jugular vein].

PMID- 18335591
TI  - [Successful treatment of patient with Fournier's phlegmon].

PMID- 18335592
TI  - [Features of "damage control" surgical tactics in severe abdominal trauma].

PMID- 18335593
TI  - [Damage control: what's new?].

PMID- 18335594
TI  - [Using of cadaver donors in clinical transplantation of kidney].

PMID- 18335595
TI  - [Surgical hystotopography of complicated duodenal ulcers. Krasnodar 2006; 297].

PMID- 18335596
TI  - [Laparoscopic removal of intraabdominal foreign body].

PMID- 18335597
TI  - [Primary-multiple synchronous cancer of stomach, thyroid and mammary glands].

PMID- 18335598
TI  - [Postnecrotic cyst of pancreas complicated with obstructive jaundice and bleeding
      into duodenum].

PMID- 18335599
TI  - [Giant ovarian cystoma].

PMID- 18335600
TI  - [Gunshot wound of head].

PMID- 18335601
TI  - [Risk factors of neurological complications in the surgery of thoracoabdominal
      aorta aneurysms].

PMID- 18335602
TI  - [Clinical and morphological aspects of chronic appendicitis].

PMID- 18335603
TI  - [Gastroduodenal bleedings at the patients with severe thermal burns].

PMID- 18335604
TI  - [History of small bowel plasty of oesophagus. To 100 years of Roux-Gertsen
      operation. Part I].

PMID- 18335605
TI  - [Nuchal cord between 37 and 42 completed weeks of gestation--diagnosis and
      prognostic value].
AB  - OBJECTIVES: To investigate the ability of transabdominal ultrasound to detect
      nuchal cord(s) between 37 and 42 completed weeks of gestation (w.g.) and to
      assess its prognostic value in relation with the perinatal outcome. METHODS:
      Transabdominal ultrasound examination using gray-scale and color Doppler imaging
      was performed in 86 singleton pregnancies between 37 and 42 completed w.g. in a
      prospective study. In 36 cases the presence of nuchal cord(s) was suspected.
      Nuchal cords were classified as with one, two or three loops. The outcome of
      labor and delivery was obtained from hospital records. RESULTS: The sensitivity
      of ultrasound for the presence of single-loop nuchal cord was 68.1%, while the
      specificity, positive and negative predictive value was 77.2%, 53.5% and 86.3%,
      respectively. CONCLUSIONS: The sensitivity and specificity of transabdominal
      ultrasound in diagnosing single-loop nuchal cord between 37 and 42 w.g. is
      relatively high. However, the detection rate for multiple loops of nuchal cord is
      even higher. Single-loop nuchal cords are not associated with increased risk of
      Cesarean section or vaginal instrumental delivery.

PMID- 18335606
TI  - [Partial mole in 18 weeks of gestation].
AB  - Partial mole is a form of gestational trophoblastic disease which occasionally
      progresses to the second trimester of pregnancy and may be associated with
      serious medical complications. We present a case report of a partial mole
      diagnosed in 18 weeks of gestation associated with severe fetal polymalformation
      sequence.

PMID- 18335607
TI  - [Sclerodermia, pregnancy and delivery].

PMID- 18335608
TI  - The medical education of generation Rx.
AB  - Psychodynamically trained psychiatrists have much to add to the education of all
      medical students, not only those who will enter Psychiatry. Aspects of the
      treatment dyad, including the formation of durable bonds between physician and
      patient, as well as the management of the manifestations of transference and
      countertransference are several of the areas of particular expertise of
      psychodynamically oriented clinicians. These principles enhance the professional
      training of the next generation of clinicians, researchers, and medical
      educators. In addition, the multiple meanings of illness for physicians and
      patients, both conscious and unconscious, can be fruitfully explored using
      psychoanalytic principles. Such an understanding can lead to greater satisfaction
      with the evaluation and treatment of illness for patients and their families, who
      are, after all, ourselves. Enlightened self-interest, then, should guide our
      increased participation in medical education.

PMID- 18335609
TI  - Childhood in World War II: German psychoanalysts remember.
AB  - The dynamic and developmental issues confronted by a generation of German
      psychoanalysts who were born between 1930 and 1945 are studied through a
      questionnaire and follow-up interviews. These individuals grew up in a society
      that, due to the collective guilt of its adults, either superimposed general self
      idealization or self-acquittal with respect to those who were identified as
      perpetrators of this trauma, or would not address or process the trauma, at all.
      In addition, these psychoanalysts, in their responses, perceived their own
      training analysts, part of the older generation, to have unconsciously, or
      perhaps even consciously, participated in the collective guilt or self
      idealization process.

PMID- 18335610
TI  - Psychodynamic concepts inherent in a biopsychosocial model of care of traumatic
      injuries.
AB  - The psychological issues facing medical and surgical patients suffering from
      traumatic injuries are numerous and varied. These injuries may occur in the
      settings of armed conflict, terrorist attack, natural disaster, or accident. The
      goal of preventing or decreasing significant and disabling psychiatric
      comorbidity can be the objective and assignment of a Psychiatry Consultation
      Liaison Service (PCLS) within the hospital setting. A comprehensive trauma
      consultation service could be designed to assist the entire medical complex in
      its response to various events. The needs of the patient, the patient's primary
      support group, and the medical staff must be considered in the development of a
      treatment strategy for the setting of a traumatic event. This article describes
      the integration of a Preventive Medical Psychiatry Service (PMP) at Walter Reed
      Army Medical Center (WRAMC) into a traditional PCLS. The PMP model is built upon
      the biopsychosocial model and psychodynamic developmental concepts.

PMID- 18335611
TI  - Combat veterans: impressions of an analytic observer in a non-analytic setting.
AB  - The hallmark presentation of combat trauma-nightmares, waking hallucinations,
      intrusive traumatic memories, and extreme affective reactions to environmental
      triggers-may best be conceptualized as part of an adaptive mechanism intended to
      protect the individual against a repetition of trauma. Combat veterans
      continuously must cope with the extreme affects that combat induced. Fear, rage,
      guilt, and grief predominate. Their mental and emotional life is complicated by a
      conscience split between war zone and civilian morality and by the special group
      dynamics of combat. Optimal clinical understanding of combat-related trauma,
      whether in a psychoanalytic or general mental health setting, requires an
      awareness of the interaction of the personal dynamics of each individual with the
      specific characteristics of their combat situation.

PMID- 18335612
TI  - Aftermath: the implicit processes of integrating traumatic experience in the
      poetry of Siegfried Sassoon.
AB  - The creation of narratives often allows individuals to bear witness to traumatic
      events. This study looked at connections between the processing of traumatic,
      affect laden experience and levels of symbolization and symmetry within the
      context of poetic expression. The sample for this pilot study is composed of
      selected works by Siegfried Sassoon (1886-1967), a British soldier-poet of the
      Great War. The language of the poems reflected the deepening trauma of the war
      experience by showing a progression toward paranoid (concrete)/symmetrical
      experiences. As the years passed and the poet was able to process the memory of
      the events, the poetry reflected a more balanced shift toward integration of
      depressive (symbolic)/asymmetrical experience. In terms of affect, the most
      significant changes were seen after Sassoon left the front and witnessed the
      flagrant dichotomy between civilian and military life. The results suggest a way
      in which traumatic events are processed. The routine horror and brutality of the
      Western Front initially lay outside of the realm of language and symbols and were
      thus highly concrete and unprocessed experiences. Time, place, and identity
      collapsed in on itself, leading to the increase of symmetrical experience, while
      the extreme "us versus them experience" of the trenches can be seen in the
      balance of asymmetrical experience. The study has implications for the treatment
      of war trauma, suggesting that writing provides a vehicle through which events
      can be processed and an internal sense of balance can be approached.

PMID- 18335613
TI  - Organ donation law in Pakistan: an overview of the current situation.

PMID- 18335614
TI  - [Persistent neonatal hypoglycaemia caused by arterial positioning of the
      umbilical venous catheter].

PMID- 18335615
TI  - Super sleuths. UF clinicians and researchers make the oral-systemic health
      connection.

PMID- 18335616
TI  - UF experts fashion prosthetic ears for young son of Olympic medalist.

PMID- 18335617
TI  - Teaching is a satisfying segue from private practice.

PMID- 18335618
TI  - Dentist of the year. Buckenheimer has always felt sense of giving.

PMID- 18335619
TI  - Case of the month. Verrucous carcinoma.

PMID- 18335620
TI  - [Relationships of microbial biomass carbon and nitrogen with particle composition
      and nitrogen mineralization potential in calcareous soil].
AB  - Taking 25 surface soil samples of calcareous soil with greater difference in
      fertility on Loess Plateau as test materials, this paper studied the
      relationships of soil microbial biomass carbon (B(C)) and nitrogen (B(N)) with
      soil nitrogen mineralization potential (N(0)), total nitrogen (TN), organic
      carbon (OC), and particle composition. The results showed that B(C) and B(N) had
      significant positive correlations with TN and OC, suggesting that B(C) and B(N)
      were highly related with soil fertility and could be used as biological indices
      of soil quality. B(C) and B(N) were highly correlated with N(0), with the
      correlation coefficient being 0.741 and 0.665, respectively (P < 0.01). B(C),
      B(N), TN, OC and N(0) all had significant positive correlations with physical
      clay (< 0.01 mm) but negative correlations with physical sand (> 0.01 mm), and
      had significant positive correlations with the ratio of physical clay to physical
      sand, indicating that soil organic matter was mainly combined with physical clay
      to form soil organic-mineral complexes.

PMID- 18335621
TI  - A radical women's rights and peace activist: Margarethe Lenore Selenka, initiator
      of the first worldwide women's peace demonstration in 1899.

PMID- 18335622
TI  - Maori health and Heaton Rhodes as minister of public health, 1912-1915.

PMID- 18335623
TI  - [Medical discourse and the invention of the homosexual: Spain, 1840-1915].

PMID- 18335624
TI  - A unique partnership: William and Lawrence Bragg and the 1915 Nobel Prize in
      Physics.

PMID- 18335625
TI  - Pay for performance--where are the nurse practitioners?

PMID- 18335626
TI  - [Human capital and economic development in Brescia: the instructional system from
      unification to the first postwar period].

PMID- 18335627
TI  - The imagined hausfrau: national identity, domesticity, and colonialism in
      Imperial Germany.

PMID- 18335628
TI  - Paris and London in the nineteenth century.

PMID- 18335629
TI  - Social thought and social action in the German empire.

PMID- 18335630
TI  - [Report from the Chief Editor's department].

PMID- 18335631
TI  - Ecstasies of the young: sexuality, the youth movement, and moral panic in Germany
      on the eve of the First World War.

PMID- 18335632
TI  - Education policy and the question of child labour: the Lancashire cotton industry
      and R.D. Denman's Bill of 1914.

PMID- 18335633
TI  - [Introductory comment: about the efficiency of CME].

PMID- 18335634
TI  - Product development of branded, packaged household goods in Britain, 1870-1914:
      Colman's, Reckitt's, and Lever Brothers.

PMID- 18335635
TI  - [Readers' letters concerning F. Keller et al: "Financial incentives and
      dialysis"].

PMID- 18335636
TI  - [Readers' letters concerning F. Keller et all: "Financial incentives and
      dialysis"].

PMID- 18335637
TI  - [Readers' letters concerning F, Keller et al: "Financial incentives and
      dialysis"].

PMID- 18335638
TI  - Making sense of mutation requires knowledge management.

PMID- 18335639
TI  - Interventing with domestic violence offenders. Introduction.

PMID- 18335640
TI  - Smokeless tobacco and some tobacco-specific N-nitrosamines.

PMID- 18335641
TI  - [The lethal alcohol intoxications and deaths due to severe drunkenness in North
      Slovakia regions (1994-1996, 2003-2005): a medicolegal comparative study].
AB  - The authors performed the complex analysis of the mortuary files (since 1994 to
      1996 and 2003 to 2005) with particular focusing on the cases of deaths caused by
      alcohol intoxication, and the cases of deaths where an alcohol played the
      dominating role, in the northern regions of Slovak republic. Based on the
      analysis mentioned, authors point out the continuous rise of alcohol abuse,
      followed by the fatal consequences for human beings. The authors are to express
      the urgent need of public discussion concerning the alcohol consumption in
      Slovakia; the phenomenon being widely tolerated by the society, thus leading to
      the number of social tragedies even in 21st century.

PMID- 18335642
TI  - [Paternity testing based on the analysis of DNA and its revision].
AB  - Paternity testing is nowadays mostly based on the analysis of DNA short tandem
      repeats (STR). Number and selection of STR loci differ according to
      identification kit producers and also particular laboratories. This article
      refers a revision of formerly excluded paternity. The cause of the mismatch was
      revealed by the enlargement of STR loci panel and reciprocal evaluation of
      samples and paternity was on the contrary confirmed. Different possibilities of
      failures, their consequences and preventions are also discussed.

PMID- 18335643
TI  - [Prior exposure of the entrance wound region from clothing in suicides].
AB  - According to an old empiric rule related to suicidal gunshot wound still in use,
      suicides will rarely shoot through their clothing, but will put it aside to
      expose the nude skin. A bullet defect in victim's clothing was often interpreted
      as a suspicious finding. In our article, which is based on retrospective
      consecutive study of gunshot fatalities from 1980 to 2004, where all autopsies
      were performed in Department of Legal Medicine in Hradec Kralove, there were 38
      cases with suicidal gunshot wound of trunk. In file of 38 cases only 3 victims
      exposed the entrance wound region from their clothing (relative frequency of only
      8%). Thus a bullet defect in clothing should not be interpreted as an absolute
      criterium, which could exclude the possibility of suicide or suggest homicide or
      an accident. But in case when gunshot victim has bared the region of the entrance
      wound from textile can this finding be interpreted as a typical indication for
      suicide.

PMID- 18335644
TI  - Clarification: 510k is premarket notification; it provides no patent or FDA
      approval.

PMID- 18335645
TI  - Early improvement in rhytides and skin laxity following treatment with a
      combination fractional laser emitting two wavelengths sequentially.
AB  - BACKGROUND: Carbon dioxide laser resurfacing remains the gold standard for the
      treatment of photoaged skin. Today, however, fewer patients will tolerate the
      postoperative downtime associated with the use of this device. Fractional
      photothermolysis was designed to overcome the disadvantages associated with
      ablative resurfacing. Prototype fractional lasers (Fraxel, Reliant Technologies
      Inc.) have required the use of blue tracking dye to give evenly spaced
      microtreatment zones, and treatments are associated with moderate levels of
      discomfort because of microtreatment zone depths reaching nearly 1000 microm.
      Newer technologies have evolved that do not require tracking dye, and are less
      painful than older prototypes because microtreatment zones are more superficial
      (100 to 300 microm) than that of the Fraxel laser. Newer devices offer advances
      in treating facial rhytides and skin laxity through the use of 2 laser
      wavelengths (1320 nm/1440 nm) emitted sequentially through a specialized
      diffractive lens array that produces high-intensity microtreatment zones
      surrounded by deeper low level heating. OBSERVATIONS: One to 3 treatments with
      this combination fractional laser device were performed on 16 Caucasian females
      with static periocular rhytides or skin laxity affecting the nasolabial crease.
      There was a 3-week period between treatments. Improvement was noted in both areas
      after a small number of treatments. CONCLUSION: The technology behind fractional
      lasers is rapidly evolving, and new devices offer significant advances over older
      prototypes.

PMID- 18335646
TI  - Reductions in thigh and infraumbilical circumference following treatment with a
      novel device combining ultrasound, suction, and massage.
AB  - Liposuction is the gold standard of body contouring procedures. Many patients,
      however, will not tolerate the invasiveness and subsequent recovery time
      associated with this procedure, despite the likelihood of superior results.
      Consequently, patients opt for minimally invasive forms of body contouring that
      require several treatments, have fewer associated side effects, and afford more
      modest improvements. The MedSculpt device is one such modality that combines
      computerized massage, vacuum suction, and ultrasound with a continuous sinusoidal
      pulse delivered at a frequency of 3 Hz. The efficacy of this device was assessed
      in the reduction of thigh and abdominal circumferences. Five patients were
      included in this pilot study. A total of 12 treatments were performed on a
      semiweekly basis to 2 abdomens and 3 pairs of thighs. Photographs and
      circumferential measurements of each area were obtained prior to, and at the
      conclusion of, the treatment course. The treatments were well tolerated and
      without side effects. The mean reduction in thigh circumference was 2.25 cm or
      4%, with a 5 cm reduction in 1 subject. Although limited improvement was seen in
      supraumbilical circumference, the mean reduction in infraumbilical circumference
      was 6.5 cm or 7.3%, with a 10 cm reduction in 1 subject. Mild improvement in skin
      tone, texture, and the appearance of cellulite was observed in all study
      participants. The results observed after 12 treatments were similar to or better
      than those seen with other minimally invasive, body contouring devices.

PMID- 18335647
TI  - Fractional photothermolysis.

PMID- 18335648
TI  - Dermabrasion in our practice.
AB  - Dermabrasion is a technique of facial resurfacing that allows the physician to
      sculpt the skin surface by surgically abrading, or planing the contours of the
      skin. User technique, device settings, and the combination of dermabrasion with
      other skin resurfacing treatments enable the physician to treat a wide variety of
      skin defects.

PMID- 18335649
TI  - A clinical study of topical Pyratine 6 for improving the appearance of
      photodamaged skin.
AB  - OBJECTIVE: Pyratine 6 has been shown to have antiaging effects in human skin
      cells. The purpose of this study is to determine the cosmetic efficacy and
      tolerance of topical Pyratine 6 (0.10%) over 12 weeks for improving the baseline
      clinical signs and symptoms of photodamaged facial skin. METHODS: A single-arm
      longitudinal study with observations at 2, 4, 8, and 12 weeks was conducted.
      Forty healthy women with mild to moderate signs of photodamaged facial skin
      applied Pyratine 6 twice daily for 12 weeks. Efficacy and safety were evaluated
      by clinical observations, digital photography, transepidermal water loss (TEWL),
      skin capacitance, and silicon replicas at each time point. RESULTS: Topical
      Pyratine 6 achieved significant improvement from baseline in roughness and skin
      moisture content after 2 weeks. After 4 weeks, significant improvement in fine
      wrinkles, mottled hyperpigmentation, and TEWL were observed. Improvements in most
      parameters were maintained throughout the remaining weeks of the study. For most
      silicon replica parameters, changes were consistent with increased skin
      smoothing. Facial erythema was reduced at 2 weeks and further reduced at 4, 8,
      and 12 weeks. Adverse effects were minimal and transient. CONCLUSIONS: Treatment
      with Pyratine 6 over 12 weeks improves roughness and skin moisturization in 2
      weeks compared to baseline and mottled hyperpigmentation and fine wrinkles in 4
      weeks compared to baseline. Reduction in facial erythema occurs as early as 2
      weeks. Adverse effects are minimal and transient.

PMID- 18335650
TI  - Photopneumatic technology for the treatment of acne vulgaris.
AB  - OBJECTIVE: Treatment of acne vulgaris with light sources necessitates multiple
      targets including Propionibacterium acnes and sebaceous glands. Traditional light
      sources such as blue light capitalize on P acnes bacteria as targets while
      infrared lasers and radiofrequency devices target the sebaceous gland. A novel
      device combining vacuum and a unique broadband light source was designed to
      combine multiple targets for the effective treatment of acne. The objective of
      this study was to demonstrate the safety and efficacy of a novel device that uses
      a combination of broadband light and pneumatic energy for the treatment of acne
      vulgaris. METHODS: In a retrospective multicenter study, clinical data were
      collected from 56 patients with mild to severe acne. Patients had been treated 2
      to 4 times with a portable photopneumatic device (Aesthera PPx, Aesthera
      Corporation, Pleasanton, CA) that delivers broadband light (400 to 1200 nm) to
      the treatment site via a hand piece. For 11 of the 56 patients, 3 independent
      physicians blinded to the study treatment or duration evaluated PPx efficacy by
      comparing photographs taken before and after PPx treatment. RESULTS: For the 56
      patients, the median physician-rated clearance increased from 50% after a single
      treatment to 90% after the fourth treatment, whereas the median patient-rated
      clearance improved from 50% after a single treatment to 78% after the fourth
      treatment. On a 4-point scale, both physician-rated and patient-rated median
      overall satisfaction levels increased from a 3 after a single treatment, to 4
      after the second, third, and fourth treatments. Clinically significant adverse
      events were not observed. For the 11 patients evaluated by photography, the
      median papule and pustule lesion counts decreased from 8 to 3 and from 2 to 0,
      respectively. Median acne severity (Burton scale) decreased from 4 before
      treatment to 2 after the final treatment, and the median improvement was 4.5
      (scale 1-5). The median erythema rating decreased from 2 before treatment to 1
      after the final treatment (scale 1-4). Adverse events were limited to mild
      erythema. The median acne clearance was 3 (scale 1-4). CONCLUSION: Photopneumatic
      technology provides a safe and effective treatment of mild to severe acne
      vulgaris.

PMID- 18335651
TI  - Visible light photopatch testing of common photocontactants in female filipino
      adults with and without melasma: a cross-sectional study.
AB  - BACKGROUND: Although consistently associated with sun exposure, melasma is common
      among sun-shy Filipino women who generally prefer to have lighter skin, use skin
      lighteners, regularly practice sun avoidance, and are more exposed to indoor
      lights. OBJECTIVE: To determine presence/absence of photocontact dermatitis in
      melasma/no-melasma patients using photopatch testing (PhPT) with standard
      photocontactants and an indoor visible light (VL) source. DESIGN: Cross-sectional
      study: random population of 40 female patients aged 30-55 years, 20 with and 20
      without melasma. The PhPT included 67 photocontactant allergens: 59 from
      Chemotechnique Diagnostics (24 fragrance, 22 North American photopatch, 13
      plants) and 8 cosmetic allergens from Skin Sciences Laboratory Inc. (Pasig,
      Philippines) in sets of paired test patches. One of the pairs was irradiated with
      a 500-watt tungsten halogen lamp as the VL source; the other was the
      nonirradiated control. The standard protocols of the North American Contact
      Dermatitis Group (NACDG) was used to examine the nonirradiated control patches
      after 48 and 72 hours, the DAPT (German/ Austrian/ Swiss Photopatch Study Group)
      was used to examine the VL-irradiated patches, and both protocols were used to
      interpret relevance of the readings as to the presence or absence of contact
      dermatitis (CD) or photocontact dermatitis (PhCD). RESULTS: Fifty-five percent of
      patients in the melasma group (N = 11/20) had 29 positive (+) PhPT reactions to
      VL-irradiated allergens (11 fragrances, 11 North American, 7 plants). In the no
      melasma group, none had (+) PhPT. This association is highly significant (P =
      0.00 using 2-tailed Fischer's exact test), such that compared to a (-) PhPT, a
      (+) PhPT has 12.67 times more likelihood to develop melasma (P = 0.05: 1.402
      114). All 29 (+) PhPT were decrescendo type, replaced by pigmentation observed up
      to 7 days suggesting phototoxic reactions, and all had (+) clinical relevance
      establishing phototoxic low-energy VL-PhCD. CONCLUSION: Melasma worsens with sun
      exposure, but this study shows that the low energy of artificial indoor VL is
      enough to react with photocontactants followed by a pigmentation response that
      may account for its clinical appearance as a mostly noninflammatory slowly
      evolving facial pigmentation.

PMID- 18335652
TI  - Treatment of hyperkeratosis with Kerafoam emollient foam (30% urea) to assess
      effectiveness and safety within a clinical setting: a case study report.
AB  - Ten patients enrolled in a single center, observational, prospective, open-label
      case study to assess the effectiveness and safety of a 28 day regimen with
      Kerafoam 30% urea emollient foam for treatment of hyperkeratosis. Clinician
      assessments of skin condition were recorded at baseline, day 14, and day 28. In
      addition, patients' ratings of the treatment impact on quality of life and skin
      condition, as well as overall satisfaction with the product were obtained. Key
      results demonstrated significant improvements in clinicians' ratings of skin
      condition at the day 14 and day 28 visits compared to baseline and significant
      improvements in patients' ratings of quality of life. No adverse events were
      reported and all patients completed the 28-day treatment regimen. Patient and
      clinician evaluations of the 30% urea emollient foam product were extremely
      favorable.

PMID- 18335653
TI  - Case reports: lisinopril-induced erythroderma in an 85-year-old male.
AB  - An 85-year-old male presented with a case of erythroderma secondary to lisinopril
      ingestion without a previous history of skin disease. While ACE inhibitors have
      been shown to elicit psoriatic erythroderma in previous cases, to our knowledge
      this is the first case report of iatrogenic erythroderma secondary to lisinopril
      in a patient without dermatologic comorbidities.

PMID- 18335654
TI  - Folliculotropic mycosis fungoides responding to bexarotene gel.
AB  - Folliculotropic mycosis fungoides (FMF) is an uncommon and potentially aggressive
      form of cutaneous T cell lymphoma (CTCL). Phototherapy, radiotherapy, and
      systemic chemotherapy are the most commonly employed treatment options, but may
      have limited success and common adverse reactions. Bexarotene gel is a topical
      retinoid X receptor (RXR) agonist with activity on the follicular unit that has
      not been previously reported in the management of FME The case of a 73-year-old
      male with FMF that responded to bexarotene gel is presented.

PMID- 18335655
TI  - Treatment approaches for advanced cutaneous melanoma.
AB  - Advanced melanoma has a poor prognosis, and standard adjuvant treatment offers
      little survival advantage. Current efforts are aimed at combining chemotherapy
      and novel immunomodulators, which these include melanoma vaccines, cytokines and
      anti-CTLA4 antibodies. Hundreds of combination therapies are currently in trials.
      All advanced melanoma patients should be considered for enrollment in a trial for
      their own benefit as well as for the advancement of melanoma treatment. Thus far,
      no single investigative approach stands out as highly effective, however, they
      all hold promise with rare patients showing durable responses. Most treatment
      protocols are evaluating combinations of adjuvant therapies, hoping to achieve a
      synergistic effect. Ongoing research into the biology of melanoma continues to
      suggest new drug targets that will block tumor progression or enhance host
      response. Until the day that an effective treatment for advanced melanoma is
      found, prevention and early detection will remain paramount in combating this
      deadly malignancy.

PMID- 18335656
TI  - Musical links to medicine.

PMID- 18335657
TI  - Medicine, music and the mind.

PMID- 18335658
TI  - A historical perspective on placebo.

PMID- 18335659
TI  - Medical deaths in pregnancy.

PMID- 18335660
TI  - Academic vice president, Royal College of Physicians.

PMID- 18335661
TI  - Evaluation of a dedicated short-stay unit for acute medical admissions.
AB  - The number of acute medical admissions to hospital continues to rise although not
      all need a prolonged stay. At the Queen Elizabeth Hospital, Gateshead, a short
      stay unit (SSU) was developed specifically for such patients. Admissions to SSU
      over the first three weeks of 2006 were assessed. A total of 209 patients were
      admitted to SSU (10 patients a day). This accounted for 35% of all admissions
      through the medical assessment unit (MAU). Of these, 149 (71%) went home within
      48 hours and a further 14 (7%) went home from SSU within 72 hours. The mean
      length of stay was 33 hours and the overall length of stay across the MAU (4.6
      days) was significantly lower than the corresponding period a year earlier (5.5
      days) (p = 0.02). The mean daily number of medical patients staying on non
      medical wards was also lower during the study period than in 2005 (11 v 38; p =
      0.015). Readmission rates and percentage bed occupancy did not change. This paper
      shows that the introduction of an SSU helps to identify and treat those patients
      with more minor illness who can often be discharged home at an earlier stage.

PMID- 18335662
TI  - The acute medical take: an outpatient specialty.
AB  - The traditional model of acute medical care involves the admission of patients to
      hospital to be assessed by a consultant and facilitate access to investigation
      and treatment. This model has, however, led to a number of problems. Firstly,
      there is high bed occupancy which restricts access and increases the risk of
      healthcare-acquired infection. Secondly, only limited training opportunities are
      offered for junior medical staff in this setting. Thirdly, patients often receive
      care from a 'generalist' rather than a 'specialist' although there is increasing
      evidence that the most appropriate specialist provides the best patient care.
      Many medical emergencies could be managed in the outpatient (ambulatory) setting
      if the appropriate facilities were available including staff, environment and
      access to investigations. Emergency outpatient clinics can provide gold standard
      emergency care by providing structure to the acute take, ensuring access to the
      most appropriate specialist and training opportunities for junior medical staff.

PMID- 18335663
TI  - Hepatology: a personal story.
AB  - When I first began my career in hepatology in October 1959, investigative and
      treatment measures for patients with liver disease were limited. It was not until
      the discovery of hepatitis B virus in 1967 and hepatitis C virus in 1989 that the
      specialty began to expand, particularly with the development of effective
      antiviral therapy. Phenomenal advances in the knowledge of immune reactions also
      led to advances in our understanding and treatment of autoimmune disorders
      affecting the liver and in the continued development of liver transplantation--a
      major success story. The new liver support devices are currently showing promise
      but on the negative side is the rising prevalence of alcohol-related liver
      disease and non-alcoholic fatty liver disease.

PMID- 18335664
TI  - Mucosal lymphocytes in the pathogenesis of the hepatic complications of
      inflammatory bowel disease.

PMID- 18335665
TI  - Recent developments in targeting liver fibrosis.

PMID- 18335666
TI  - How does the brain process music?
AB  - The organisation of the musical brain is a major focus of interest in
      contemporary neuroscience. This reflects the increasing sophistication of tools
      (especially imaging techniques) to examine brain anatomy and function in health
      and disease, and the recognition that music provides unique insights into a
      number of aspects of nonverbal brain function. The emerging picture is complex
      but coherent, and moves beyond older ideas of music as the province of a single
      brain area or hemisphere to the concept of music as a 'whole-brain' phenomenon.
      Music engages a distributed set of cortical modules that process different
      perceptual, cognitive and emotional components with varying selectivity. 'Why'
      rather than 'how' the brain processes music is a key challenge for the future.

PMID- 18335667
TI  - Self-poisoning: current trends and practice in a U.K. teaching hospital.
AB  - The epidemiology of deliberate self-poisoning presentations to the emergency
      department (ED) of Ninewells Hospital was reviewed over a six-month period. The
      results were related to previously published Scottish data. During the six month
      period, 530 patients presented (2.1% of total). There was a female preponderance
      with over 65% of patients aged less than 40 years. Patients lived more commonly
      in areas of higher deprivation. The drugs most commonly involved were paracetamol
      (39.25%) and antidepressants (35.1%). Of the presentatons 80.2% required no
      treatment apart from basic observations. Only 1.51% received activated charcoal
      and no gastric lavages were performed. Of the presentations, 75.6% were
      discharged after observation in the ED, 8.9% were admitted to a psychiatric
      hospital and 5.5% were admitted to general medicine department. Deliberate self
      poisoning continues to be a major cause of hospital admissions in Scotland. In
      Tayside, it is predominantly a problem of the young and socially deprived.
      Consistent with recent national trends, paracetamol was the most common drug
      relating to overdose. The use of an ED observation ward is supported as a vast
      majority of patients are admitted for less than 24 hours and require no active
      treatment.

PMID- 18335668
TI  - Recent developments in acute coronary syndromes.
AB  - Coronary artery disease is the leading cause of death in the UK with a high
      clinical, social and economic burden. The management of acute coronary syndromes
      is rapidly evolving and clinicians are constantly challenged with incorporating
      new clinical pathways and guidelines into their practices. It is important for
      clinicians to have a sound working knowledge of acute coronary syndromes, and be
      updated on the emerging evidence to guide therapy and improve outcomes in these
      patients.

PMID- 18335669
TI  - Ethical planning for an influenza pandemic.
AB  - A U.K. Pandemic Influenza Contingency Plan was developed in 2006 but little
      research has since been carried out as to how ethically acceptable it will be to
      society. A survey containing two hypothetical scenarios was distributed to 1,018
      hospital staff. The survey considered their attitudes to the professional and
      ethical responsibilities of healthcare workers, and to resource allocation on the
      intensive care unit (ICU). Of those distributed, 406 (40%) surveys were returned.
      During a pandemic, 320 (79%) healthcare professionals would continue to work and
      339 (83%) felt it would be unprofessional for doctors to leave work. Only 218
      (54%) chose the same patient for the last ICU bed. Most staff surveyed felt they
      should (professionally) and would (voluntarily) work during a pandemic despite
      high personal risk. A wide diversity of opinion existed regarding resource
      allocation of ICU beds. These ethical issues require open debate to ensure U.K.
      pandemic plans are ethically acceptable and practically applicable.

PMID- 18335670
TI  - The contribution of a pharmacy admissions service to patient care.
AB  - The aim of this study was to determine the impact of two specialised admissions
      pharmacists on an acute medical admissions ward. For a one-week period,
      contributions made to the medical post-take ward round (PTWR), the number of drug
      histories taken and interventions made as a result, and the availability of
      medication needed on discharge were documented. An average of 1.1 contributions
      per patient were made on the PTWR; a large proportion of these concerned
      therapeutic choice. Pharmacists also intervened to stop medication due to adverse
      drug reactions in 12% (n=10) of contributions. Fifty-two drug histories were
      checked by a pharmacist, resulting in 61 interventions (1.1 interventions per
      patient). The majority of interventions resulted from the unintentional omission
      of a regular medication (65%, n=39). Only 24% (n=29) of items needed on discharge
      had to be dispensed in pharmacy and 33% (n=41) were available as patients' own
      drugs.

PMID- 18335671
TI  - The impact of patenting on DNA diagnostic practice.
AB  - Patents on genes often cover the gene sequence and the link between a disease and
      mutations in a gene, rather than a technology for the identification of mutations
      per se. Normally, patents are important for encouraging the development of new
      diagnostic tools and kits, but there is evidence that they can have severely
      deleterious effects on the delivery of genetic services. The difference largely
      depends on the licensing policy of the patent holder. This article describes
      different ways in which patents are used in this context and how the effects may
      be mitigated.

PMID- 18335672
TI  - Practice-based commissioning: implications for secondary care.
AB  - General practitioner (GP) practice-based commissioning (PBC) is a much debated
      politically driven NHS innovation at a time of ongoing change. Unlike GP
      fundholding it is envisaged that PBC will involve all GP practices by 2008. A
      possible outcome is that some current secondary care services may be commissioned
      in primary care in the form of local enhanced services or intermediate clinics
      and run by GPs with special interests. Examples where this has occurred are
      diabetes and anticoagulation. Similarly, private providers may be commissioned.
      Inevitably there will be an impact on hospital services through a possible
      reduction in funding and consultants being subcontracted to provide services in
      primary care. Issues such as clinical governance and cost-effectiveness, however,
      require evaluation to determine the potential effect on the working relationships
      and so the interface between generalists and specialists.

PMID- 18335673
TI  - The Mental Capacity Act 2007 and capacity assessments: a guide for the non
      psychiatrist.
AB  - The Mental Capacity Act 2007 affects doctors in all areas of practice. The act
      recognises that capacity is a 'balance of probability rather than certainty', and
      based on this it attempts to 'maximise capacity' in an individual, so to
      facilitate a decision-making process. The act comprises five key principles as
      well as a test to determine lack of capacity. It also alludes to areas such as
      consent by proxy, restraint and capacity, and regulations regarding clinical
      research. This paper provides a brief background into the fundamental tenets of
      the act as well as a simple scheme for assessing capacity in hospital inpatients.
      It also looks at what physicians should be aware of and what will be required of
      them, particularly from a medico-legal perspective.

PMID- 18335674
TI  - Chronic spinal cord injury: management of patients in acute hospital settings.
AB  - Spinal cord injury (SCI) is a lifelong condition affecting over 40,000 people in
      the UK. When an individual with established SCI is admitted to hospital for a
      procedure or because of illness, hospital teams need to manage both the acute
      condition and the spinal cord injury. These guidelines aim to assist in their
      assessment and management to avoid the common problems of hospital-acquired
      morbidity in this potentially vulnerable group of people. Key steps are: gaining
      an understanding of the common patho-physiological consequences of SCI; listening
      to the person and their family who are often expert in managing the condition;
      and maintaining close contact with the individual's regular team/specialist
      spinal cord injury centre.

PMID- 18335675
TI  - The mystery and the paradox of scientific medicine.

PMID- 18335676
TI  - Developing concepts in allodynic pain.

PMID- 18335677
TI  - Complementary and alternative medicine.

PMID- 18335678
TI  - Epidemiology and clinical presentation.

PMID- 18335679
TI  - Investigation and management of the poisoned patient.

PMID- 18335680
TI  - Toxins that affect the cardiovascular system.

PMID- 18335681
TI  - Analgesics.

PMID- 18335682
TI  - Recreational drug toxicity.

PMID- 18335683
TI  - Never say die?

PMID- 18335684
TI  - Serotonin syndrome secondary to fluoxetine precipitated by radiation induced
      cerebral vasculopathy.

PMID- 18335686
TI  - College comment on 'Thousands starving in U.K. hospitals'.

PMID- 18335685
TI  - Editorial: 'Thousands starving in U.K. hospitals'; letter 1.

PMID- 18335687
TI  - Lesson of the month.

PMID- 18335688
TI  - Impact of a European working time directive-compliant working pattern on delivery
      of medical specialty teaching for senior house officers in a teaching hospital.

PMID- 18335689
TI  - The diagnosis of recurrent venous thrombosis--can a risk stratified approach at
      initial presentation be helpful?

PMID- 18335690
TI  - Complementary and alternative medicine: is it right for our patients (or us)?

PMID- 18335691
TI  - What's the significance of evidenced-based practice? Do we really need levels of
      evidence?

PMID- 18335692
TI  - Sacral nerve neuromodulation (InterStim). Part I: Review of the InterStim system.
AB  - Sacral nerve neuromodulation is accepted technology for patients with refractory
      urge incontinence, urinary frequency syndrome, and chronic urinary retention.
      This treatment consists of an implantable lead and neurostimulator (battery)
      using light electrical pulses to stimulate the sacral nerve controlling the
      bladder and other muscles that control urinary function. This article reviews the
      indications for neuromodulation as well as patient selection and testing phases
      associated with this technology.

PMID- 18335693
TI  - Sacral nerve neuromodulation (InterStim). Part II: Review of programming.
AB  - While it is not critical for health care providers to know everything about the
      InterStim (sacral nerve neuromodulation) equipment and programming, Part II of
      this series will increase the provider's knowledge about InterStim therapy by
      describing the equipment, delineating patient education needs, and discussing the
      art of programming. This article will assist the provider in trouble shooting the
      system and provide some insight into the patient's therapy.

PMID- 18335694
TI  - Sacral nerve neuromodulation (InterStim). Part III: Case studies.
AB  - Part III of this sacral nerve neuromodulation (InterStim therapy) series
      describes two case studies. This article coalesces all the concepts associated
      with InterStim therapy, including criteria for patient selection, education,
      surgery, programming, and return visits. The first case study describes a woman
      with urgency-frequency and urinary incontinence. The second case study discusses
      a woman with a diagnosis of urinary retention. These case studies provide the
      reader with successful outcomes with InterStim and its use as a viable treatment
      option when patients meet the selection criteria.

PMID- 18335695
TI  - Test-retest reliability of the Urge-Urinary Distress Inventory and Female Sexual
      Function Index in women with multiple sclerosis.
AB  - Test-retest reliability of the Urge-Urinary Distress Inventory (U-UDI) and the
      Female Sexual Function Index (FSFI) was assessed in women with multiple sclerosis
      (MS) because it was undetermined whether or not either instrument would yield
      reliable and valid results in this population. Data from this study suggest that
      these tools can be reliably used to assess community-dwelling women with mild
      gait disability and MS-associated symptoms of urinary distress and sexual
      dysfunction.

PMID- 18335696
TI  - 'I'd rather just go on as I am'--pelvic floor care preferences of frail, elderly
      women in residential care.
AB  - Little is known about how frail, elderly women in assisted living and long-term
      care facilities view pelvic floor dysfunctions and treatments. Twenty-five
      residents reflect on these issues, and quality of life.

PMID- 18335697
TI  - Unintentional transurethral Foley catheterization of the right renal pelvis.
AB  - This case study describes a 23-year-old woman who had an unintentional blind
      placement of a 16 Fr Foley catheter into her right ureter with inflation of the
      balloon in the right renal pelvis. Pertinent medical history/presentation,
      clinical interactions, and clinical implications are discussed.

PMID- 18335698
TI  - Effects of a modified yeast supplement on cold/flu symptoms.
AB  - A yeast-based product (EpiCor, a dried Saccharomyces cerevisiae fermentate) was
      compared to placebo to determine effects on the incidence and duration of cold
      and flu-like symptoms in healthy subjects recently vaccinated for seasonal
      influenza. In a 12-week, randomized, double-blind, placebo-controlled clinical
      trial, 116 participants received daily supplementation with 500 mg of EpiCor or
      placebo for 12 weeks. Data collected included periodic in-clinic examinations and
      serologic evaluations at baseline, 6- and 12-weeks. Subjects also utilized a
      standardized self-report symptom diary during the study. Participants receiving
      the yeast-based product had significantly fewer symptoms and significantly
      shorter duration of symptoms when compared with subjects taking a placebo.

PMID- 18335699
TI  - Predicting urinary tract infections in a urogynecology population.
AB  - A retrospective chart review was performed on all new patients presenting to a
      urogynecology clinic. Urine dipsticks, symptoms, and cultures were evaluated to
      identify urinary tract infections. The most sensitive result was for the
      combination of nitrites or leukocytes (59%) without significant change in
      specificity (95%) for either result individually. The addition of the
      statistically significant symptoms did not improve the outcome. Based on these
      findings, it was determined that no combination of dipstick and/or symptoms
      adequately predicted an infection to the point that a recommendation to dispense
      with the need for a culture in this urogynecology population could be made.

PMID- 18335700
TI  - Adding to the evidence base: a critique of 'predicting urinary tract infections
      in a urogynecology population'.

PMID- 18335701
TI  - Traditional Vietnamese health and healing.
AB  - Approximately 1.2 million Vietnamese live in the United States. Health care
      providers need to understand that this population differs greatly from other
      cultures depending on gender, religion, generation, reason for migration, enclave
      identity, educational level, and language preference. This article will explore
      the history, communication practices, biocultural ecology, and health care
      principles among this population.

PMID- 18335702
TI  - Brewer's/baker's yeast (Saccharomyces cerevisiae) and preventive medicine: Part
      II.
AB  - Yeast is the term generally applied to a unicellular fungus, and there are
      hundreds of species now identified. One of the most notable and well-known
      species of yeast in health and wellness is known as Saccharomyces cerevisiae,
      which is also known by its more common names, brewer's yeast or baker's yeast.
      Typically, brewer's yeast is used as a protein supplement, energy booster, immune
      enhancer, or other vehicle where other compounds can be inserted to create a
      commercialized health product. For example, one of the most notable positive
      findings was the encouraging results from a large randomized trial of adults
      recently vaccinated for seasonal influenza who also received an over-the-counter
      daily adjuvant modified brewer's yeast-based product (EpiCor) to prevent colds
      and flu symptoms. The modified yeast-based product significantly reduced the
      incidence and duration of this common condition. Yeast-based technology is also
      being used as a molecular mechanistic model of caloric restriction (CR) with the
      goal of improving the human life span. The current and potential impact of yeast
      based technology in medicine is encouraging and should receive more attention,
      but the recent preliminary positive results of CR in humans may be in part due to
      what has been already learned from brewer's yeast.

PMID- 18335703
TI  - The Walter C. Randall Lecture. Facing the dark side: research misconduct and
      strategies to improve self regulation.

PMID- 18335704
TI  - A role for scientists in evolution education.

PMID- 18335705
TI  - Selecting your first postdoctoral position.

PMID- 18335706
TI  - Riding a bus while seated in a wheelchair: A pilot study of attitudes and
      behavior regarding safety practices.
AB  - A total of 283 wheelchair-seated bus riders responded to a 35-item Web-based
      survey investigating their experiences on public, fixed-route buses. The survey
      addressed the use of wheelchair tiedowns and occupant restraint systems (WTORS),
      the attitudes and behaviors of wheelchair users toward the use of this equipment,
      and the transit experience. Results indicate that consistent use of four-point
      tiedown and occupant restraint systems is fairly low. Only 33.2% of the
      participants reported always securing their wheelchair, and 62.2% reported using
      occupant restraints consistently. A preference for fixed-route over para-transit
      was related to larger city size. Implementation of transit agency policy
      regarding WTORS was found to be inconsistent. Easier-to-use WTORS and improved
      operator training in larger transit agencies would likely increase the correct
      use of safety equipment and improve wheelchair users' bus-riding experiences.

PMID- 18335707
TI  - Motor vehicle transportation use and related adverse events among persons who use
      wheelchairs.
AB  - For the 2.2 million people who use wheelchairs in the United States,
      transportation is often needed for independence in the community. The purpose of
      this study was to investigate the characteristics of transportation use in a
      population of wheelchair users and to examine the motor vehicle crash involvement
      and injury frequency of these users. Responses were collected from 596
      individuals from June 2002 to November 2003. Approximately 20% of the sample
      population was involved in a motor vehicle crash in the previous 3 years,
      resulting in a rate of 3.6 accidents/incidents per 100,000 miles traveled.
      Crashes were defined as any motor vehicle accident that the person was involved
      in during the previous 3 years. Persons who did not transfer from their
      wheelchair were more likely to be involved in a crash than those individuals who
      transferred to vehicle seats. Eighteen percent of the population reported
      involvement in a non-crash-related incident during the previous 3 years.
      Passengers reported a greater frequency of non-crash-related injuries than did
      drivers. The results of this study provide documentation of transportation use
      and safety in people who use wheelchairs. It provides insight into the risk of
      crash and injury in this population.

PMID- 18335708
TI  - Wheelchair tiedown and occupant restraint system issues in the real world and the
      virtual world: combining qualitative and quantitative research approaches.
AB  - The Americans with Disabilities Act requires that transit providers accommodate
      passengers who use "common wheelchairs" when traveling in a motor vehicle.
      Wheelchair tiedown and occupant restraint systems are commonly used to secure
      wheelchairs and restrain occupants in fixed-route and demand route transit
      vehicles. Throughout the 17 years since the Americans with Disabilities Act has
      been in effect, transit providers have complained about the usability of
      wheelchair tiedown and occupant restraint systems, and improper securement has
      been linked to injuries among wheelchair users during "nonimpact incidents." This
      research study explored the use of wheelchair tiedown and occupant restraint
      systems in actual practice and the potential risks of misuse to wheelchair-seated
      individuals. The qualitative research conducted in this study revealed that
      improper wheelchair securement (i.e. using less than four tiedown straps) can be
      fairly common practice in fixed-route transit. In addition, preliminary computer
      simulations show that improper wheelchair securement in emergency driving
      conditions may place wheelchair occupants at a greater risk of injury. It should
      be noted, however, that this is a pilot study and has its limitations. For
      example, qualitative data were gathered from one metropolitan area transit
      provider across a limited range of vehicle and wheelchair types. Additionally,
      the computer simulation model used in this study was originally validated for
      impact situations.

PMID- 18335709
TI  - Bus dynamics for mobility-aid securement design.
AB  - Mobility-aid securement on large urban transit buses has been designed without an
      adequate knowledge of either the accelerations that are likely to occur in normal
      operations or the maximum accelerations that are possible short of an impact
      accident. These normal operation accelerations are important because they are the
      source of motion and corresponding sense of insecurity on the part of the
      passenger when riding in a mobility-aid on a bus. This paper describes the
      equipment and procedures used to measure the distribution of accelerations to be
      expected on large buses in normal transit service and the maximum accelerations
      possible during extreme maneuvering for six different sizes and types of transit
      buses. Included in the tests were low-floor buses of different lengths, a high
      floor bus, a 40-ft (12.2-m) low-floor double-decker bus, and a 60-ft (18.3-m) low
      floor articulated bus. During in-service tests, the accelerations were generally
      a function of the driver. In maneuvering tests, the mechanics of the bus design
      were the controlling factors. The results show that, in general, normal driving
      accelerations were typically less than 0.2 g in all directions and very rarely
      greater than 0.4 g. In the event of an emergency-driving situation, forward and
      turning accelerations may reach 0.4 g and stopping may result in 0.8 g.

PMID- 18335710
TI  - Towards the next generation of wheelchair securement--development of a
      demonstration UDIG-compatible wheelchair docking device.
AB  - The main purpose of this study was to demonstrate that an auto-docking device
      (ADD) could be produced that would meet the requirements for the universal
      interface contained in the evolving International Standard Organization (ISO10542
      3) standard and also meet Americans with Disabilities Act (ADA) regulations
      within the United States. A secondary purpose was to produce a practical design
      that directly addressed the most pressing securement deficiencies being
      experienced by transit users and providers that had promise of transfer to
      commercial availability. ADD development has demonstrated that a standards
      compatible ADD can be produced that meets the rigorous crash test requirements of
      ISO10542-3. Follow-up in-vehicle testing indicated the need for design refinement
      in order to prevent movement of an occupied manual wheelchair in excess of the 2
      in. maximum requirement stipulated in the 1990 ADA. A user focus group provided
      feedback on the utility of the overall universal auto-docking concept, as well as
      guidance for improvement to control interfaces that would be located in the
      wheelchair and driver stations. The partnership with Kinedyne Inc., a
      manufacturer of securement devices, provided the industry-based focus that
      resulted in the cost containment and marketing expertise necessary to make the
      ADD a viable commercial product.

PMID- 18335711
TI  - Development and validation of a frontal impact 6-year-old occupant and wheelchair
      computer model.
AB  - Many children with disabilities use their wheelchair as a vehicle seat when
      traveling. To date, few studies have focused on pediatric wheelchair users in
      transit. A computer model representing a manual pediatric wheelchair seated with
      a Hybrid III 6-year-old anthropomorphic test device subjected to a 20-g/48-kph
      (30-mph) frontal crash was developed in MADYMO. The wheelchair was secured using
      a 4-point tiedown system, and the occupant was restrained using a 3-point belt
      system. The time history profiles of the computer model were tuned to those of
      the sled tests. The peak value for key variables was compared between the sled
      tests and the model. To evaluate model variable time histories, Pearson's
      correlation coefficients (r) between the sled test and the model outcome measures
      were determined. The correlation coefficients ranged from .86 to .95, with an
      average r of .91. This indicates that there are "high" correlations between the
      model and sled tests across all variables. The pediatric wheelchair model
      developed and validated in this study will provide a foundation for studying the
      response of a manual pediatric wheelchair in frontal impacts and associated
      injury risks for pediatric wheelchair users.

PMID- 18335712
TI  - Toward development of effective custom child restraint systems in motor vehicles.
AB  - Traveling safely in motor vehicles can be challenging for many families who have
      young children with physical disabilities. Harnesses, simple adaptations, and
      special child restraint systems are available, but sometimes these devices do not
      adequately meet the unique postural support requirements of children with complex
      seating needs. Faced with no alternative, parents may choose to use the custom
      seating system from a wheeled mobility device to support their children in the
      family car. Transporting children in this way can increase the risk of motor
      vehicle-related injury because custom seating systems are not designed to meet
      the requirements of federal motor vehicle safety regulations. We studied whether
      assistive technology suppliers could build custom child restraint systems that
      met the crashworthiness requirements of a safety standard for production child
      restraint systems. We provided technical instructions to 10 suppliers from
      different parts of North America so they could each build a custom restraint
      system using a transit frame that we designed. This approach allowed suppliers to
      make custom seats that could be attached to the transit frame using special
      connection hardware. We crash tested the 10 custom child restraint systems to
      evaluate the effectiveness of our transit frame design and fabrication
      instructions. Six custom restraint systems met the dynamic performance
      requirements of the stringent Canada Motor Vehicle Safety Standard 213.3. The
      remaining four systems did not meet the compliance criteria due to the failure of
      postural belt assemblies or seat securement hardware. We recommend that future
      research include similar effectiveness studies to support the introduction of
      technical requirements for adaptive seating systems that improve occupant safety
      and are practical for wheelchair users, their families, and assistive technology
      professionals to implement.

PMID- 18335713
TI  - The effect of glycosaminoglycan depletion on the friction and deformation of
      articular cartilage.
AB  - Glycosaminoglycans (GAGs) have been shown to be responsible for the interstitial
      fluid pressurization of articular cartilage and hence its compressive stiffness
      and load-bearing properties. Contradictory evidence has been presented in the
      literature on the effect of depleting GAGs on the friction properties of
      articular cartilage. The aim of this study was to investigate the effect of
      depleting GAGs on the friction and deformation characteristics of articular
      cartilage under different tribological conditions. A pin-on-plate machine was
      utilized to measure the coefficient of friction of native and chondroitinase ABC
      (CaseABC)-treated articular cartilage under two different models: static (4 mm/s
      start-up velocity) and dynamic (4 mm/s sliding velocity; 4 mm stroke length)
      under a load of 25 N (0.4 MPa contact stress) and with phosphate-buffered saline
      as the lubricant. Indentation tests were carried out at 1 N and 2 N loads (0.14
      MPa and 0.28 MPa contact stress levels) to study the deformation characteristics
      of both native and GAG-depleted cartilage samples. CaseABC treatment rendered the
      cartilage tissue soft owing to the loss of compressive stiffness and a sulphated
      sugar assay confirmed the loss of GAGs from the cartilage samples. CaseABC
      treatment significantly increased (by more than 50 per cent) the friction levels
      in the dynamic model (p < 0.05) at higher loading times owing to the loss of
      biphasic lubrication. CaseABC treatment had no effect on friction in the static
      model in which the cartilage surfaces did not have an opportunity to recover
      fluid because of static loading unlike the cartilage tissue in the dynamic model,
      in which translation of the cartilage surfaces was involved, ensuring effective
      biphasic lubrication. Therefore the depletion of GAGs had a smaller effect on the
      coefficient of friction for the static model. Indentation tests showed that GAG
      depleted cartilage samples had a lower elastic modulus and higher permeability
      than native tissue. These results corroborate the role of GAGs in the compressive
      and friction properties of articular cartilage and emphasize the need for
      developing strategies to control GAG loss from diseased articular cartilage
      tissue.

PMID- 18335714
TI  - Strain pattern following surface replacement of the hip.
AB  - The aim is to compare the strain pattern in intact and resurfaced femurs using
      validated third-generation composite femurs and rosette strain gauges. The
      rosette strain gauges were applied to an intact and a resurfaced third-generation
      composite femur at three sites: the narrowest part of the lateral surface of the
      neck, the narrowest part of the medial surface of the neck, and the medial
      surface at the level of the lesser trochanter. The maximum and minimum principal
      strains were calculated at axial loads of 600, 800, and 1000 N. Further tests
      were carried out with an additional abductor load. The maximum principal strains
      in the resurfaced femur were approximately 50 per cent higher in the lateral
      surface of the neck and about 25 per cent higher in the lesser trochanteric
      region than in the intact femur. Inclusion of the abductor force decreased the
      strains in both the intact and the resurfaced femurs, particularly at the lateral
      surface of the femoral neck. Increased strain at the lateral surface of the
      femoral neck following hip resurfacing could be a cause of neck fracture,
      particularly if there are other predisposing factors such as notching of the
      femoral neck and/or abductor dysfunction. Meticulous repair of the abductors is
      warranted if a lateral approach is used.

PMID- 18335715
TI  - Particle attrition of alpha-tricalcium phosphate: effect on mechanical, handling,
      and injectability properties of calcium phosphate cements.
AB  - Calcium phosphate bone cements are currently used in a range of applications;
      however, their low compressive strength and brittle failure mechanics have
      limited their widespread application. The aim of this study was to improve the
      mechanical performance of the calcium phosphate cement by means of particle
      reduction of the powder components involved. alpha-Tricalcium phosphate (alpha
      TCP) powder was produced and subsequently reacted with water to form a calcium
      deficient hydroxyapatite in the form of a biocompatible and resorbable cement. It
      was postulated that the reduction of the alpha-TCP particle size would result in
      a faster-setting reaction and stronger cement. Three milling techniques were
      explored and their methods optimized. The techniques included the traditional
      ball-milling technique and two newer techniques, namely cryogenic and planetary
      milling. Particle size analysis through laser diffraction and scanning electron
      microscopy was conducted. Compressive strength, setting times and injectability
      characteristics of the curing cement were determined. It was observed that all
      three techniques were efficient methods of particle reduction and the mechanical,
      setting and injectability properties were significantly improved by the reduction
      in particle size of the alpha-TCP powder. However, agglomerations of alpha
      tricalcium phosphate resulted in a reduction in compressive strength and
      injectability after prolonged milling periods, irrespective of milling technique.

PMID- 18335716
TI  - Tibiofemoral cartilage thickness distribution and its correlation with
      anthropometric variables.
AB  - The objective of this study was to determine tibiofemoral cartilage thickness
      distribution, and to investigate the relationship between cartilage geometry and
      anthropometric variables. In this study, 20 magnetic resonance examinations of
      the knee from normal individuals were reconstructed to provide three-dimensional
      models of the knee joint, including bony and cartilage surfaces. Three regions
      were defined on the articular surface, and the cartilage thickness distribution
      along each of these was determined. Statistically significant differences between
      femoral and tibial regions were examined using the paired Student t test in
      Microsoft Excel. Correlations were investigated using the correlation tool in
      Microsoft Excel. The average tibial cartilage thickness was found to be 2.76 mm
      and the average femoral cartilage thickness was 2.75 mm. Significant correlations
      exist between the tibia cartilage thickness and body height (R = 0.60; P < 0.05)
      and weight (R = 0.64; P < 0.05). Significant correlations exist between the
      femoral cartilage volume and the body height (R = 0.736; P < 0.01) and weight (R
      = 0.855; P < 0.01). It is suggested that the distribution and correlations of
      cartilage distribution indicate adaptation in response to mechanical loading.
      Information regarding cartilage thickness and volume distribution as found in
      this study may be useful in diagnosing and monitoring cartilage loss in patients
      with degenerative joint disease.

PMID- 18335717
TI  - Determination of muscle fatigue using dynamically embedded signals.
AB  - This paper explores a new method of analysing muscle fatigue within the muscles
      predominantly used during microsurgery. The captured electromyographic (EMG) data
      retrieved from these muscles are analysed for any defining patterns relating to
      muscle fatigue. The analysis consists of dynamically embedding the EMG signals
      from a single muscle channel into an embedded matrix. The muscle fatigue is
      determined by defining its entropy characterized by the singular values of the
      dynamically embedded (DE) matrix. The paper compares this new method with the
      traditional method of using mean frequency shifts in the EMG signal's power
      spectral density. Linear regressions are fitted to the results from both methods,
      and the coefficients of variation of both their slope and point of intercept are
      determined. It is shown that the complexity method is slightly more robust in
      that the coefficient of variation for the DE method has lower variability than
      the conventional method of mean frequency analysis.

PMID- 18335718
TI  - A novel approach to the prediction of musculotendon paths.
AB  - One of the most important aspects of the modelling of musculoskeletal systems is
      the determination of muscle moment arms which are dependent upon the paths of the
      muscles. These paths are often required to wrap around passive structures that
      can be modelled as simple geometric shapes. A novel technique for the prediction
      of the paths of muscles modelled as strings when wrapping around smooth
      analytical surfaces is presented. The theory of geodesics is used to calculate
      the shortest path of the string on the surface and a smoothness constraint is
      used to determine the correct solutions for the string path between insertions.
      The application of the technique to tapered cylinders and ellipsoids is presented
      as an extension of previous work on right-circular cylinders and spheres. The
      technique is assessed with reference to a particular biomechanical scenario;
      string lengths and moment arms are calculated and compared with alternative
      approximate methods. This illustrates the potential of the technique to provide
      more accurate muscle moment arm predictions.

PMID- 18335719
TI  - Towards a standard in assessment of bone cutting for total knee replacement.
AB  - Arthroplasty outcome is influenced by the 'quality' of bone preparation for
      implant insertion. Surgeons face increasing choices of technique and
      instrumentation, yet clinical scoring methods assess the overall outcome and
      patient satisfaction but not the bone cuts directly. 'Quality management' of bone
      reshaping is needed to evaluate different bone cutting methods and computer
      assisted orthopaedic surgery (CAOS) systems. Analyses and experiments in this
      study were formulated for measurement and computation of four quantitative
      characteristics of bone preparation 'quality' and produced a highly condensed
      index for each. These represented (a) surface finish of cuts, (b) implant
      fit/looseness possible with the cut shape, (c) implant location/misalignment, and
      (d) accuracy of individual planar cuts. Assessment of synthetic bone cuts
      verified the robustness of the method for wide application in arthroplasty
      intraoperatively, in vitro and for comparing navigation systems.

PMID- 18335720
TI  - The effects of trochlear groove geometry on patellofemoral joint stability--a
      computer model study.
AB  - The effect of the variation in the femoral groove geometry on patellofemoral
      joint stability was studied using a two-dimensional transverse plane model with
      deformable articular surfaces. The femoral and patellar bony structures were
      modelled as rigid bodies with their profiles expressed by splines. The articular
      cartilage was discretized into compression springs, distributed along the femoral
      and patellar profiles, based on the rigid-body spring model. The medial and
      lateral retinacula were modelled as linear tensile springs, and the quadriceps
      muscles and patellar tendon as strings with known tension. The anatomical data
      were obtained from the transverse plane magnetic resonance images of a normal
      knee flexed at 20 degrees and from the literature. A dynamic analysis approach
      was employed to solve the governing equations of the model, i.e. three static
      equilibrium equations of the patella and a constraint equation for each cartilage
      spring, explicitly. The results of the model suggest that alteration of the
      sulcus angle from 139 degrees to 169 degrees causes a lateral shift and tilt of
      less than 3 mm and 4 degrees. This effect increased slightly with increasing
      total quadriceps force, however, to significantly more than 7 mm and 18 degrees
      respectively when the medial retinaculum was released. It was suggested that this
      might be the combined effect of the medial retinaculum deficiency and trochlear
      dysplasia that is responsible for patellar subluxation and, particularly,
      dislocation disorders.

PMID- 18335721
TI  - Experimental set-up and sensory glove interface for microsurgery.
AB  - One of the most fundamental prerequisites for successful microsurgery is
      thoughtful and adequate training. A combination of knowledge, technical skill,
      and decision making directly influences the surgical outcome. This study aims to
      analyse microsurgical hand coordinations quantitatively and to study the utility
      of a sensory glove interface in identifying the hand coordination patterns during
      microsurgery. A sensory glove interface used to measure the angular flexion
      extension movements of the major interphalangeal joints of the hand, the grasp
      pressure, and the relative hand movements has been developed. Experiments of two
      suturing techniques were conducted with five experienced microsurgeons, and
      microsurgery practice was examined. The custom sensory glove interface required
      both signal conditioning and amplification which was directly interfaced with a
      custom-designed LABView software code. The sensory glove interface was calibrated
      using regression techniques and the set-up was validated using the Bland-Altman
      correlation technique. The hand coordination patterns were analysed using
      principal-component analysis. Pareto plots showing the contribution of the
      principal components were analysed. The contributions of the first two sensory
      data components have also been compared with hand coordination studies. The
      temporal variations provided new insights into the underlying synergetic
      mechanisms and in particular the relation between different suture techniques on
      grasp pressure.

PMID- 18335722
TI  - Reality-augmented virtual fluoroscopy for computer-assisted diaphyseal long bone
      fracture osteosynthesis: a novel technique and feasibility study results.
AB  - In this paper, a novel technique to create a reality-augmented virtual
      fluoroscopy for computer-assisted diaphyseal long bone fracture osteosynthesis
      and feasibility study results are presented. With this novel technique,
      repositioning of bone fragments during closed fracture reduction and
      osteosynthesis can lead to image updates in the virtual imaging planes of all
      acquired images without any radiation. The technique is achieved with a two-stage
      method. After acquiring a few (normally two) calibrated fluoroscopic images and
      before fracture reduction, the first stage, data preparation, interactively
      identifies and segments the bone fragments from the background in each image.
      After that, the second stage, image updates, repositions the fragment projection
      on to each virtual imaging plane in real time during fracture reduction and
      osteosynthesis using an OpenGL-based texture warping. Combined with a
      photorealistic virtual implant model rendering technique, the present technique
      allows the control of a closed indirect fracture osteosynthesis in the real world
      through direct insight into the virtual world. The first clinical study results
      show the reduction in the X-ray radiation to the patient as well as to the
      surgical team, and the improved operative precision, guaranteeing more safety for
      the patient. Furthermore, based on the experiences gained from this clinical
      study, two technical enhancements are proposed. One focuses on eliminating the
      user interactions with automated identifications and segmentations of bone
      fragments. The other focuses on providing non-photorealistic implant
      visualization. Further experiments are performed to validate the effectiveness of
      the proposed enhancements.

PMID- 18335723
TI  - Finite element analysis of a subtrochanteric fractured femur with dynamic hip
      screw, dynamic condylar screw, and proximal femur nail implants--a comparative
      study.
AB  - Selection of the correct type of implant for fracture fixation has become a very
      interesting problem in the orthopaedic community. The present work studies the
      biomechanical behaviour of the femur with three different implant configurations
      for simple transverse subtrochanteric fracture and the intact femur using finite
      element analysis. The implants considered in this study are as follows: dynamic
      hip screw (DHS), dynamic condylar screw (DCS), and proximal femur nail (PFN). The
      modelling software Unigraphics and finite element simulation software ANSYS are
      used for the present analysis. The three implants are compared for deflection,
      stress, and strains. The simulation also includes modelling of the cortical
      defect near the fracture. An estimation of the critical depth of the cortical
      defect based on the von Mises stress is obtained using this study on the DHS
      implant. The displacement and principal stress on the proximal femur have been
      compared for all the implant models. The stresses on the cortical screws for DCS
      and DHS implants have also been compared. The result shows that the DHS and DCS
      implants behave in a similar way to the intact femur compared with the PFN
      implant.

PMID- 18335724
TI  - The use of acellular matrices for the tissue engineering of cardiac valves.
AB  - Tissue-engineering approaches to cardiac valve replacement have made considerable
      advances over recent years and it is likely that this application will realize
      clinical success in the near future. Research in this area has been driven by the
      inadequacy of the currently available cardiac valve prostheses for younger
      patients who require multiple reoperations as they grow and develop. Tissue
      engineering has the potential to provide a valve capable of the same growth,
      repair, and regeneration as a natural valve and could improve outcomes for
      patients of all ages. Owing to the function and physical environment of the
      cardiac valve, the development of tissue-engineered replacements is unusual in
      that the biomechanical properties of the construct must dominate the biological
      properties in order for the valve to be functional at the time of implantation.
      As a result of this, conventional tissue-engineering scaffolds based on
      biodegradable polymers or collagen may not at present be suitable in this
      situation because of their initial limited strength. Research into the use of
      acellular xenogeneic and allogeneic matrices for tissue-engineered heart valves
      has consequently become extremely popular since the biomechanical properties of
      the valve can potentially be preserved with an optimal decellularization
      technique that removes the cells without damaging the matrix. A number of
      acellular scaffolds have already been tested clinically both unseeded and
      preseeded with cells and these have met with variable results. This article
      reviews the concepts involved and the advantages and disadvantages of the
      different approaches to tissue engineering a living cardiac valve.

PMID- 18335725
TI  - Smooth surface micro finite element modelling of a cancellous bone analogue
      material.
AB  - Tetrahedral finite element meshes with smooth surfaces can be created from
      computed tomography scans of cancellous bone in order to evaluate its mechanical
      properties. Image processing before creation of the mesh can affect the accuracy
      of determined mechanical properties. For a cancellous bone analogue, threshold,
      mesh density and surface smoothing parameters used in mesh generation were varied
      and the mechanical properties predicted by the resulting meshes were compared to
      experimental results. This study has shown that threshold selection is vital for
      accurate determination of volume fraction and resulting mechanical properties.

PMID- 18335726
TI  - A history of the Academy of Gold Foil Operators: Chapter II.

PMID- 18335727
TI  - Comparative clinical evaluation of different treatment approaches using a
      microfilled resin composite and a compomer in Class III cavities: two-year
      results.
AB  - This study evaluated the 24-month clinical performance of a microfilled composite
      using a one-bottle bonding system and a compomer that uses one-bottle bonding
      systems, which include a non-rinse conditioner or 36% phosphoric acid gel in
      Class III cavities. Each patient received three restorations due to primary
      caries of the anterior teeth, resulting in a total of 96 restorations. Three
      types of restoration/adhesive combinations were used: a microfilled resin
      composite (Filtek A110) with a one-bottle bonding system (Single Bond); a
      polyacid-modified resin composite (compomer) (Dyract AP) with a filled one-bottle
      bonding system (Prime & Bond NT) using 36% phosphoric acid pretreatment and a
      polyacid-modified resin composite (compomer) (Dyract AP) with a filled one-bottle
      bonding system (Prime & Bond NT) using a non-rinse conditioner (NRC) and a self
      priming pretreatment. At baseline and one- and two-year recalls, color match,
      marginal discoloration, wear or loss of anatomical form, caries, marginal
      adaptation and surface texture of the restorations were evaluated by two
      experienced, calibrated examiners using the modified Ryge criteria. After two
      years, one restoration from each group had a rating of Charlie (C) for both color
      match and marginal discoloration and needed to be replaced. Therefore, the
      failure rate was 3.6% (success rate: 96.4%) for each group at the end of two
      years. Statistical analysis showed no significant differences among the three
      groups in color match, marginal discoloration, wear or loss of anatomical form,
      marginal adaptation and surface texture after two years. Also, no statistically
      significant differences were determined for each group with respect to color
      match, marginal discoloration, wear or loss of anatomical form, marginal
      adaptation and surface texture at the end of two years.

PMID- 18335728
TI  - Clinical evaluation of in-office dental bleaching treatments with and without the
      use of light-activation sources.
AB  - This study clinically evaluated the alteration of color, color stability, dental
      sensitivity and gingival irritation on patients undergoing dental bleaching using
      varying bleaching methods and light-activation sources. According to pre
      established criteria, 40 patients were selected and randomly divided into four
      groups (n=10): Group 1--35% Hydrogen Peroxide (HP); Group 2--35% HP plus Halogen
      Curing Light XL 3000 (3M/ESPE); Group 3--35% HP plus Demetron LED (Kerr) and
      Group 4--35% HP plus LED/LASER (Bio-art). For all groups, there were two sessions
      of bleaching with 35% HP, with a one week break between sessions. At each
      bleaching session, three applications of the bleaching gel were used. Two methods
      of shade evaluation were performed before and after the first week, second week,
      first month and after six months of the bleaching treatment. These methods were
      VITA Easyshade Spectrophotometer and Vita Classical Shade Guide. Statistical
      analysis using ANOVA demonstrated equality between the participating groups when
      evaluating the group and time variables. The In-Office dental bleaching
      treatments of vital teeth with 35% HP did not prove to be more effective when
      light sources were used. There was no difference in color stability between
      groups until the sixth month of evaluation.

PMID- 18335729
TI  - Cytotoxicity of composite materials polymerized with LED curing units.
AB  - The proper intensity and illumination time of a curing light is of great
      importance for the complete polymerization of resin composites and long-lasting
      resin composite restorations. Inadequately cured resin composites can have a
      cytotoxic effect on pulp tissue by releasing unreacted monomers. This study
      determined whether there is any difference in cytotoxicity between composite
      materials illuminated with different curing modes of LED curing units. Thin
      layers of two composite materials were polymerized using three different modes of
      the Bluephase C8 LED curing unit: a high intensity mode (HIP-800 mW/cm2, 20
      seconds), a soft-start mode (SOF-650 mW/cm2 first 5 seconds, 800 mW/cm2 next 25
      seconds) and a low intensity mode (LOP-650 mW/cm2, 30 seconds). Lymphocyte
      cultures were treated with both polymerized and unpolymerized composites using
      one of the modes stated above. Cells were analyzed using the trypan blue
      exclusion test, the acridine orange/ethidium bromide dying technique and an
      alkaline comet assay. Significant cytotoxicity was observed for 120 mg of
      unpolymerized composites and those polymerized with the HIP polymerization mode.
      A significant level of DNA damage was detected for 120 mg of unpolymerized
      composites. However, curing via the LOP program exhibited the lowest
      genotoxicity. Longer curing time with lower intensity results in less
      cytotoxicity than shorter curing exposure using a higher intensity of light
      emitted from the curing light source.

PMID- 18335730
TI  - Leakage pathway of Class V cavities restored with different flowable resin
      composite restorations.
AB  - This study investigated the leakage pathway of facial and lingual Class V
      cavities restored with different flowable resin composites bonded with one
      bonding agent by examining the resin/dentin interface. Forty Class V cavities
      were etched with 37% phosphoric acid gel; Single Bond dental adhesive was
      applied, then the cavities were randomly divided into four groups (n=10). Three
      groups were restored with one of three flowable resin composites (Grandio Flow,
      Filtek Flow and Admira Flow). The fourth group was restored with Z250 (hybrid
      resin composite) to serve as a control. The specimens were then placed in 50% w/v
      silver nitrate solution for 24 hours and immersed in a photodeveloping solution
      for eight hours. Thereafter, the specimens were sectioned bucco-lingually,
      polished, mounted on stubs, gold sputter coated and examined by scanning electron
      microscope. Silver particle penetration length with and without gap formation was
      measured directly on the scanning electron microscope monitor and calculated as a
      percentage of the total length of the cut dentin surface that was penetrated by
      silver nitrate. The data were analyzed with one-way ANOVA and Tukey HSD test. The
      groups restored with Filtek Flow and Admira Flow showed a microleakage pattern
      where silver nitrate penetration was observed with gap formation at the
      tooth/restoration interface and Filtek Flow recorded significantly higher leakage
      than Admira Flow. Grandio Flow showed similar marginal adaptation to Z250 resin
      composite with no gap formation at the interface. However, silver ions had
      penetrated beneath the resin-impregnated layer in cavities restored with Grandio
      Flow and Z250, indicating nanoleakage occurred. This study suggests that
      volumetric shrinkage in resin composites remains a problem. Although some new
      technologies are trying to solve the problem of composite shrinkage, the bonding
      system used in this study did not achieve perfect sealing at the
      restoration/dentin interface. This might affect durability of the bond to dentin.

PMID- 18335731
TI  - Fracture resistance and gap formation of MOD restorations: influence of
      restorative technique, bevel preparation and water storage.
AB  - This in vitro study evaluated the effect of technique, use of a bevel and thermal
      cycling on the fracture resistance and gap formation of resin composite MOD
      restorations. Fracture resistance was measured on standard MOD cavities prepared
      in 100 upper premolars that were stored for 24 hours and 6 months with 1000
      thermal cycles. Subgroups (n=10) were: beveled or non-beveled preparations and
      direct restorations (Adper Single Bond/Filtek Z250) and indirect restorations
      (prepolymerized Filtek Z250 cemented with Rely XARC). Ten sound teeth and 10
      specimens with MOD preparations without restorations served as the positive and
      negative controls, respectively. The specimens were subjected to axial
      compression in a universal testing machine at a crosshead speed of 0.5 mm/minute.
      Failure patterns were analyzed by stereomicroscopy (40x). To evaluate gap
      presence or absence, proximal box cavities were prepared in 24 human third molars
      that were restored as described above. The specimens were evaluated under SEM
      examination after 24 hours and six months. Data were statistically analyzed by
      ANOVA and multiple comparison tests at the 0.05 level of significance. After 24
      hours, the beveled restorations exhibited higher fracture strength values than
      the non-beveled restorations, and all groups showed resistance similar or
      superior to sound teeth. After six months, the highest fracture resistance was
      obtained for beveled inlays and the lowest values were observed for direct
      restorations with butt joints. Thermal cycling decreased fracture resistance in
      the majority of the groups. The main fracture pattern observed was cohesive
      failure in the material, but adhesive failures increased over time, especially in
      the non-beveled restorations. Under SEM examination, no difference was observed
      among the groups after 24 hours. However, after six months, the beveled
      restorations exhibited no gap formation. It was concluded that storage with
      thermal cycling decreased fracture resistance, bevels improved fracture
      resistance and, in general, indirect restorations were not superior to direct
      restorations.

PMID- 18335732
TI  - The influence of one-step polishing systems on the surface roughness and
      microhardness of nanocomposites.
AB  - OBJECTIVES: This in vitro study evaluated the surface roughness and microhardness
      of nanocomposites that contain nanoparticles and a microhybrid composite finished
      and polished with two different one-step polishing systems and a conventional
      multi-step polishing system. METHODS AND MATERIALS: The materials evaluated were
      Filtek Supreme XT, Grandio, Ceram X, Aelite Aesthetic Enamel, Tetric EvoCeram and
      Filtek Z250. A total of 240 specimens (10-mm in diameter, 2 mm thick) were
      fabricated for both tests (n=120 each test) in a plexiglass mold covered with a
      Mylar strip. After polymerization, five specimens per group received no polishing
      treatment and served as the control for both tests. For each composite group
      (n=15), the specimens were randomly divided into three polishing systems: PoGo,
      OptraPol and Sof-Lex. All polishing systems were applied according to the
      manufacturers' instructions after being ground wet with 1200 grid silicon carbide
      paper. The surface roughness values were determined using a profilometer. The
      microhardness measurements were performed using a digital microhardness tester
      (load 500 g; dwell time 15 seconds). The data were analyzed using the one-way
      ANOVA test at a significance level of 0.05 for both tests. Multiple comparison
      was performed with the Duncan Multiple Range test. RESULTS: The smoothest
      surfaces were achieved under Mylar strips in all composite groups (p<0.05). There
      were no statistically significant differences between polishing systems in the
      Filtek Supreme XT, Ceram X, Aelite Aesthetic Enamel and Grandio groups for
      surface roughness (p>0.05). In the Tetric EvoCeram group, Sof-Lex exhibited the
      highest roughness values. No statistically significant differences were evaluated
      between polishing systems (p>0.05); whereas, the surfaces under Mylar Strip
      showed statistically significant lower values than the polished surfaces in terms
      of microhardness (p<0.05). CONCLUSION: One-step polishing systems may be
      successfully used for polishing nanocomposites.

PMID- 18335733
TI  - Adhesion to Er:YAG laser-prepared dentin after long-term water storage and
      thermocycling.
AB  - This in vitro study evaluated the microtensile bond strength of a resin composite
      to Er:YAG-prepared dentin after long-term storage and thermocycling. Eighty
      bovine incisors were selected and their roots removed. The crowns were ground to
      expose superficial dentin. The samples were randomly divided according to cavity
      preparation method (I-Er:YAG laser and II-carbide bur). Subsequently, an etch &
      rinse adhesive system was applied and the samples were restored with a resin
      composite. The samples were subdivided according to time of water storage
      (WS)/number of thermocycles (TC) performed: A) 24 hours WS/no TC; B) 7 days
      WS/500 TC; C) 1 month WS/2,000 TC; D) 6 months WS/12,000 TC. The teeth were
      sectioned in sticks with a cross-sectional area of 1.0-mm2, which were loaded in
      tension in a universal testing machine. The data were subjected to two-way ANOVA,
      Scheffe and Fisher's tests at a 5% level. In general, the bur-prepared group
      displayed higher microtensile bond strength values than the laser-treated group.
      Based on one-month water stbrage and 2,000 thermocycles, the performance of the
      tested adhesive system to Er:YAG-laser irradiated dentin was negatively affected
      (Group IC), while adhesion of the bur-prepared group decreased only within six
      months of water storage combined with 12,000 thermocycles (Group IID). It may be
      concluded that adhesion to the Er:YAG laser cavity preparation was more affected
      by the methods used for simulating degradation of the adhesive interface.

PMID- 18335734
TI  - Evaluation of the cervical integrity during occlusal loading of Class II
      restorations.
AB  - There are many concerns regarding the clinical behavior of packable composite
      restorations in Class II cavities, particularly when those restorations are
      subjected to axial mechanical loads. This study evaluated microleakage in vitro
      in proximal vertical "slot"-type cavities with walls located in enamel and
      dentin, filled with packable composite, associated or not associated with a
      flowable composite, a reinforced light-curing glass-ionomer or a compomer, after
      being submitted to occlusal load cycling. These preparations were subjected to
      either occlusal load cycling or no occlusal load cycling. Eighty human molars
      with enamel and dentin margins were treated with standardized cavity preparations
      (proximal vertical "slot" preparations). After completing the filling process
      using a packable composite (Filtek P60) with or without a cervical increment of
      flowable composite (Filtek flow), light-curing glass-ionomer (Vitremer) or
      compomer (Dyract AP), the molars were separated into two groups: control (without
      occlusal loading) and test, in which 4,000 one-second cycles of 150 N occlusal
      loading were applied. All 80 teeth were submitted to a microleakage test, then
      evaluated utilizing silver nitrate dye penetration. Significant statistical
      differences (Wilcoxon test, p<0.05) in the amount of leakage in enamel and dentin
      were found in both the control and test groups. After a paired comparison of the
      control and test groups, a significant statistical difference was found at the
      enamel level (Mann-Whitney test, p<0.05). In dentin, the only statistically
      significant difference found was the relation to the flow material. The Kruskal
      Wallis test did not detect any statistically significant difference in the amount
      of leakage among the four materials studied, with a 5% level of significance for
      both enamel and dentin. Based on this data, it was concluded that restorations
      with margins located in dentin had greater microleakage than those restorations
      with margins located in enamel. When the samples were submitted to occlusal
      loading, they were negatively influenced, which increased microleakage values in
      enamel and dentin. There was no statistically significant difference among the
      four tested materials, when comparing their performance.

PMID- 18335735
TI  - Effect of antibacterial varnishes applied to root dentin on shear bond strength
      of tooth-colored restorative materials.
AB  - This study investigated the effect of certain varnishes on the bond strength of
      different tooth-colored restorative materials applied to root dentin. One-hundred
      and eighty tooth slabs, including mesial and distal surfaces, were attained
      through dividing the teeth, then embedding them in methylmethacrylate. The root
      surfaces were ground flat through cementum, exposing the dentin. The samples were
      then randomly divided into three main groups: Group 1: Cervitec; Group 2: Fluor
      Protector and Group 3: No applications (control). Cervitec and Fluor Protector
      were applied to the root dentin surfaces according to the manufacturer's
      instructions. All the samples were kept in artificial saliva for six months. Each
      main group was subdivided into five groups of 12 teeth each: Group A: Flowable
      Resin Composite (Grandio Flow); Group B: Microhybrid Resin Composite (Artemis);
      Group C: Polyacid Modified Resin Composite (Dyract Extra); Group D: Resin
      Modified Glass Ionomer Cement (Vitremer) and Group E: Conventional Glass-Ionomer
      Cement (Ionofil Molar). Restorative materials were applied to the root dentin
      surfaces using a cylindrical mold. After thermocycling (1000 cycles, 5 degrees
      C/55 degrees C, dwell time 30 seconds), the shear bond strength of the restored
      samples was determined by a universal testing machine (Zwick Test Machine, Zwick
      GmbH & Co, Ulm, Germany) at a 5 mm/minute crosshead speed. Failure mode was
      determined under a stereomicroscope. The data were evaluated statistically by
      using one-way Analysis of Variance and Duncan tests (p< or =0.05). In the
      fluoride varnish group, all of the restorative materials except for Ionofil
      Molar, showed lower bond strengths when compared to the control group (p<0.05).
      In the Cervitec group, Artemis and Dyract Extra showed lower bond strengths;
      whereas, Ionofil Molar showed a higher bond strength than the control group
      (p<0.05). The highest percentage of cohesive fracture was observed in Artemis and
      Dyract Extra in the control group.

PMID- 18335736
TI  - Effect of pre-heating resin composite on restoration microleakage.
AB  - Improving the adaptation of resin composites during placement is necessary to
      increase durability and reduce microleakage. Flowable resin liners have been
      introduced to improve adaptation in composite restorations. In addition, a device
      that lowers the viscosity of regular dental composites has been introduced
      (Calset, AdDent Inc, Danbury, CT, USA). This device lowers the viscosity of
      composites by preheating them to 54.4 degrees C, which should lead to improved
      adaptation. This study compared microleakage in Class II composite restorations
      prepared using: 1) preheated resin composite, 2) unheated composite and 3) a
      flowable liner followed by unheated composite. Class II cavities were prepared on
      the mesial and distal surfaces of extracted third molars. Ten preparations were
      restored with resin composite (Esthet-X, Dentsply, York, PA, USA) for each of the
      following four techniques: Control (Esthet-X with Prime & Bond NT, Dentsply),
      Flowable (f) (as Control but used Esthet-X Flow liner), Preheated (p) (as Control
      but with preheating composite to 54.4 degrees C) and Delay (d) (as Preheated but
      followed by a 15-second delay before curing). The teeth were restored, finished,
      stored in distilled water for 24 hours, then thermocycled between water bath
      temperatures of 5 degrees C and 55 degrees C with a one-minute dwell time for
      1000 cycles. Tooth apices were sealed with epoxy and varnish was applied to
      within 1 mm of the restoration margins. The teeth were placed in 0.5% basic
      fuschin dye for 24 hours, rinsed, then embedded in self-curing resin. The
      embedded teeth were sectioned mesiodistally with a slow-speed diamond saw,
      providing multiple sections per restoration. Microleakage was rated by two
      evaluators using a 0-4 ordinal scale at the occlusal and cervical margins of each
      restoration and light microscopy (40x). The data were analyzed with Kruskal
      Wallis ANOVA and pairwise testing with the Sign test (alpha=0.05). No statistical
      differences were observed among materials at the occlusal margin. However, at the
      cervical margin, the preheated samples P showed statistically lower microleakage
      than the controls and all other treatments. The D samples showed higher
      microleakage than the P and F samples. Ranked sum scores for the cervical were D
      (4516), C (3974), F (2756) and P (1958). There was a statistically greater amount
      of leakage at the cervical margins compared to the occlusal p<0.05. Preheating
      the composite resulted in significantly less microleakage at the cervical margins
      compared to the flowable liner and control. Delaying light curing of the
      preheated composite for 15 seconds (D) was counterproductive and led to increased
      microleakage.

PMID- 18335737
TI  - Durability of enamel bonding using two-step self-etch systems on ground and
      unground enamel.
AB  - This study examined the early and long-term microtensile bond strengths (MTBS)
      and interfacial enamel gap formation (IGW) of two-step self-etch systems to
      unground and ground enamel. Resin composite (Filtek Z250) buildups were bonded to
      proximal enamel surfaces (unground, bur-cut or SiC-treated enamel) of third
      molars after the application of four self-etch adhesives: a mild (Clearfil SE
      Bond [SE]), two moderate (Optibond Solo Plus Self-Etch Primer [SO] and AdheSE
      [AD]) and a strong adhesive (Tyrian Self Priming Etchant + One Step Plus [TY])
      and two etch-and-rinse adhesive systems (Single Bond [SB] and Scotchbond Multi
      Purpose Plus [SBMP]). Ten tooth halves were assigned for each adhesive. After
      storage in water (24 hours/37 degrees C), the bonded specimens were sectioned
      into beams (0.9 mm2) and subjected to microTBS (0.5 mm/minute) or interfacial gap
      width measurement (stereomicroscope at 400x) either immediately (IM) or after 12
      months (12M) of water storage. The data were analyzed by three-way repeated
      measures ANOVA and Tukey's test (alpha=0.05). No gap formation was observed in
      any experimental condition. The microTBS in the Si-C paper and diamond bur groups
      were similar and greater than the unground group only for the moderate self-etch
      systems (SO and AD). No reductions in bond strength values were observed after 12
      months of water storage, regardless of the adhesive evaluated.

PMID- 18335738
TI  - Microtensile dentin and enamel bond strengths of recent self-etching resins.
AB  - In this study, the microtensile bond strengths of resin composites to dentin and
      enamel produced by recently introduced self-etching resins were determined.
      Included were two adhesives with self-etching primers, Clearfil SE (Kuraray) and
      Peak SE (Ultradent), four self-etching adhesives, Optibond All-In-One (Kerr),
      Clearfil S3 (Kuraray), Adper Prompt L-Pop (3M ESPE) and iBond (Heraeus Kulzer)
      and, as a positive control, PQ1 (Ultradent), an etch-and-rinse adhesive. Each
      product was evaluated using the same hybrid resin composite, Z250 (3M ESPE).
      Testing was performed after 48 hours using a "non-trimming" microtensile test at
      a crosshead speed of 0.6 mm/minute. Sample size was five teeth per group, with
      the value for each tooth calculated by averaging the bond strengths of seven
      beams derived from it. Mean values in MPa (SD) for dentin were: Clearfil SE 81.6
      (3.5),a Peak SE 80.3 (9.9),a PQ1 73.4 (4.9),a,b Optibond All-In-One 64.4 (5.9),b
      Clearfil S3 62.5 (2.2),b,c iBond 51.0 (4.0)c and Prompt L-Pop 33.9 (6.4).d Mean
      values in MPa (SD) for enamel were: PQ1 55.6 (2.5),a Clearfil SE 54.1 (5.4),a
      Prompt L-Pop 54.0 (5.4),a Peak SE 51.8 (1.5),a,b Clearfil S3 44.3 (5.2),b,c
      Optibond All-In-One 40.1 (2.1)c,d and iBond 33.8 (3.3).d (Values for each
      substrate with the same letter were not significantly different, one-way ANOVA,
      Tukey-Kramer Multiple Comparison Test, p<0.05.) Compared to the positive control,
      PQ1, only adhesives with self-etching primers, Clearfil SE and Peak SE, were as
      effective in bonding to both enamel and dentin. With the exception of Prompt L
      Pop, scanning electron micrographs of the etched enamel surface produced by self
      etching products indicated far less surface topography than conventional etching,
      even for self-etching primer systems producing the same bond strengths as the
      etch-and-rinse adhesive.

PMID- 18335739
TI  - Microleakage in overflared root canals restored with different fiber reinforced
      dowels.
AB  - This study evaluated microleakage in overflared root canals restored with four
      different types of adhesively-luted fiber-reinforced dowels: DT Light Post (LP),
      Glassix (GL), Ribbond (RB) and StickTech Post (ST). Forty non-carious, single
      rooted mandibular human premolars with straight root canals were prepared using a
      step-back technique and obturated with gutta-percha using lateral condensation.
      The restored roots were randomly divided into four groups (n=10). The root canals
      were overprepared, creating an overflared dowel space, and each dowel was
      adhesively luted using a total-etched adhesive (Single Bond) and dual
      polymerizing luting agent (RelyX ARC). All specimens were thermal cycled 1000
      times between 5 degrees C and 55 degrees C and stored in 2% methylene-blue
      solution for one week. The teeth were cut horizontally into three consecutive
      sections: apical (A), middle (M) and coronal (C). Each section was digitally
      photographed from the occlusal direction under a stereomicroscope. The images
      were transferred to a PC and stored in TIFF format. For each image, dye
      penetration was estimated as the ratio of methylene-blue-infiltrated surface
      divided by total dentin surfaces. The data were compared and statistically
      analyzed using the Kruskal-Wallis test (p<.05). The Mann-Whitney U test was used
      to compute multiple pairwise comparisons to determine differences between the
      experimental groups (p=.083). Dentin-luting agent fiber-reinforced dowel (FRD)
      interfaces were evaluated under a scanning electron microscope. Scanning electron
      microscopy (SEM) showed detachment of the luting resin from the dentin surface in
      varying degrees in all specimens evaluated. All groups showed considerable
      leakage at the sections evaluated. Significant differences were demonstrated
      between LP-RB for the apical and middle sections and between GL-RB, LP-RB and ST
      RB for the coronal sections (p<.0083). Among the FRDs evaluated, the individually
      shaped polyethylene-reinforced dowel (Ribbond) showed the least overall leakage.

PMID- 18335740
TI  - A simple method of preventing hypersensitivity in contra-lateral teeth during
      restorative procedures.

PMID- 18335741
TI  - Stain vs caries.

PMID- 18335742
TI  - [Otologic manifestations of Wegener's granulomatosis].
AB  - OBJECTIVE: To evaluate the clinical features, pathologic diagnosis and laboratory
      test of otologic manifestation in Wegener's granulomatosis (WG). METHODS:
      Fourteen eases of WG with ear involvement were reviewed. The clinical course,
      method of treatment and outcomes in all cases were evaluated. Diagnosis of WG was
      made when the patients had clinical findings, clear histologic findings and a
      positive titer of antineutrophil cytoplasmic autoantibodies (ANCA). RESULTS In
      all 14 cases, the most frequent finding was chronic otitis media Sensorineural
      hearing loss was present in 1 case and facial nerve paralysis was present in 2
      cases separately. There were 5 patients whose otologic manifestations were the
      primary involvement of WG. Fourteen cases had positive histologic diagnosis of WC
      while 13 cases were confirmed positive for ANCA. All patients were treated with
      glucocorticoids, immunosuppressive drugs, and finally got marked improvement.
      CONCLUSIONS: WG should he included in the differential diagnosis in cases of
      atypical inflammatory states of the ear, facial nerve paralysis and sensorineural
      hearing loss. Early diagnosis was made basing on the histologic findings and a
      positive titer of ANCA. Appropriate treatment were important to improve the
      otologic manifestations of WG.

PMID- 18335743
TI  - [Effect of multi-technique of intact canal and scute rebuilding in treatment of
      middle ear cholesteatoma].
AB  - OBJECTIVE: To assess the results of multi-technique with intact canal and scute
      rebuild operation for middle ear cholesteatoma. METHODS: Analysis of 113 cases
      (males 60, females 53, with mean 42.7 years old), of which with double ears of 11
      cases, and totally 124 ears (11 ears for one review, an ear for third time
      review, and totally 137 operations) was retrospectively performed. Ten cases less
      than 19 years old were operated from September 2001 to January 2006 for middle
      ear cholesteatoma as well as ossiculoplasty with intact canal and scute rebuild
      etc multi-technique. All cases were followed up for a mean (36.58 +/- 20.47)
      months. RESULTS: There were 118 ears (95.2%) without cholesteatoma recurrence.
      Six ears were found cholesteatoma recurrence. Other 6 post-operation ears with
      drum re-perforation and hearing drop were re-operated. The pre-operation air-bone
      gap (ABG, average of 0.5, 1, 2 kHz) of 124 ears, with in initial 112 ears, was
      (33. 61 +/- 12.35) dB, while that of post-operation ABG was (13.58 +/- 9. 27) dB,
      by partnership t test, t = 18.35, P < 0.01. The pre-operation ABG in reviewed 12
      ears at the first pre-operation was (38.83 +/- 12.43) dB, but post-operation ABG
      (10.38 +/- 8.99) dB, by partnership t test, t = 5.38, P = 0.00022. The ABG
      closure to within 20 dB was tested in 100 ears while ABG over 20 dB but air
      conduct (AC) in 40 dB was in 6 ears, and then as succeed was in 106 ears (85.5%).
      ABG closure within 10 dB was in 50 ears and though ABG over 10 dB but ABG reduced
      over 30 dB was in 9 ears (59/124, 47.6%) as which as best result. Bone conduct
      (BC) threshold was tested of 21 ears (16.93%) with raise 1-9 dB, of 42 ears
      (33.9%) with no change and of 61 ears (49.2%) with descend 1-28 dB. Of 10 cases
      less than 19 years old post-operation ABG was (8.80 +/- 5.27) dB, which indicated
      that all cases was as succeed. CONCLUSIONS: Using intact canal and scute rebuild
      etc multi-technique a normal canal, hearing improvement and very low recurrent
      could be gained for middle ear cholesteatoma, especially in juvenile and
      children. The multi-technique should be almost no damage for hearing bone
      conduct.

PMID- 18335744
TI  - [Etiological factor analysis of facial nerve paralysis due to chronic
      inflammation of middle ear].
AB  - OBJECTIVE: To discuss the etiological factors of facial nerve paralysis due to
      chronic inflammation of middle ear. METHODS: This retrospective research included
      41 patients operated for facial nerve paralysis due to chronic inflammation of
      middle ear. Careful exploration was made in facial canal in order to identify
      pathological tissue involvement. Pathological examination was performed in all
      operative specimens. RESULTS: Four intact fallopian canals were observed. There
      was a defect on the fallopian canal in 37 patients (90%) and it was most commonly
      located on the tympanic segment of the canal (89%). Pathological report was
      cholesteatoma, granulation and tuberculosis, which was found in 24 cases (59%) 14
      cases (34%) and 3 cases (7%), respectively. CONCLUSIONS: Facial nerve paralysis
      due to chronic inflammation of middle ear was frequently relevant with
      cholesteatoma,the tympanic segment of the fallopian canal was most location to be
      involved in. Its major factor was the infection spreading along the nerve tissue,
      but not atrophy due to compression. The defect on the fallopian canal was not
      necessary for infection diffusion.

PMID- 18335745
TI  - [Frequency of SLC26A4 IVS7-2A > G mutation in patients with severe to profound
      hearing loss from different area and ethnic group in China].
AB  - OBJECTIVE: To carry out molecular epidemiology study of SLC26A4 IVS7-2 A > G
      mutation in large Chinese deaf population and to provide evidence for fast
      screening and gene diagnosis of enlarged vestibular aqueduct syndrome (EVAS).
      METHODS: A total of 1979 patients with non-syndromic hearing loss(NSHL) underwent
      questionnaire and PCR for IVSA > G mutation detection of SLC26A4 gene. RESULTS:
      All 245 patients (12.38%) with homozygotes and heterozygotes IVS7-2 A > G
      mutation were found among the 1979 NSHL It showed statistically significant
      difference among north and northeast, northwest, east and southeast, southwest
      and central area in China. (chi2 = 34.4899, P < 0.05). Carrier frequency of the
      central area (27.52%) was notably higher than southwest area (6.69%). The IVS7-2
      A > G mutation was most frequently found in Han deaf groups (13.88%). Tibetan,
      Hui, and other western minorities were lower than Han deaf population (chi2 =
      35.4456, P < 0.05). CONCLUSIONS: A high SLC26A4 IVS7-2 A > G mutation frequency
      for deafness in Chinese patients was found. Detection of the pathogenic mutations
      was bringing the possibility to detect EVAS at an early stage. Moreover, it might
      help to establish diverse diagnostic strategies toward differently ethical deaf
      population in different region of China.

PMID- 18335746
TI  - [Spiral computed tomography analysis of fronto-ethmoidal cells in normal
      subjects].
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of
      frontoethmoidal cells in normal Chinese subjects. METHODS: Two hundred and two
      Chinese subjects without symptoms of frontal sinus disease were undergone spiral
      computed tomography (CT). The multiplanar reconstruction images were evaluated
      using a standard triplanar reconstruction protocol on a computer workstation.
      RESULTS: There were 121 males and 81 females. The mean age was (39.4 +/- 13.5)
      years. Of all the frontal cells identified in 159 sides (39.4%) of frontal
      recesses, the prevalence of type I, type II, type III and type cells were 24.3%
      (98 sides), 6.9% (28 sides), 8.2% (33 sides) and 0% (0 side) respectively.
      Suprabulbar cell, supraorbital ethmoid cells, and frontal bulbar cell were
      identified in 148 sides (36.6%) Jian-hu, 22 sides (5.4%), and 36 sides (8.9%)
      respectively. While the interfrontal septal cells was found in 25 patients
      (12.4%). The prevalence of agger nasi cell was 94. 1% (380 sides). Two hundred
      and forty-four uncinate processes (60.4%) had one superior attachment for each
      uncinate process; the other 160 uncinate processes (39.6%) had two superior
      attachments for each uncinate process. The single superior attachment of the
      uncinate process into the surrounding structures was identified to have the
      following distribution: 53.0% (n=214) to the lamina papyracea, 5.2% (n=21) to the
      middle turbinate, 2.2% (n=9) to the skull base. Most of the uncinate process' two
      superior attachments were either into the lamina papyracea and the skull base
      (27.5%, n=111) or into the lamina papyracea and the middle turbinate (8.7%,
      n=35). The other 14 uncinate processes (3.5%) superiorly attached to the skull
      base and the middle turbinate. The prevalence of recessus terminalis was 89.1%
      (n=360). CONCLUSION: The result demonstrated the normal frontal recess
      pneumatization patterns in normal Chinese.

PMID- 18335747
TI  - [Bacteriological study on adult chronic sinusitis operated after endoscopic sinus
      surgery].
AB  - OBJECTIVE: To explore the bacteria isolated from middle nasal meatus, maxillary
      sinus, ethmoid sinus and postoperative cavity of patients with chronic
      rhinosinusitis and their characteristics of antibiotic resistance. METHODS:
      Eighty-seven patients with chronic rhinosinusitis were operated on by ESS to
      obtain the pus specimen for bacterial culture and antibiotic susceptibility test,
      before and 1 month, 3 months and 6 months after operation. RESULTS: Totally 645
      strains (26 species) of bacteria were detected in 464 specimens [total positive
      rate was 78.9% (366/464)], in which aerobic bacteria was 95.3% (615/645). Gram
      negative bacteria and gram positive bacteria were 51.2% (330/645) and 48.8%
      (315/645), respectively. There was supernumerary tendency in detectable rate of
      gram negative bacteria isolated from postoperative groups. The main pathogens of
      postoperative patients were gram negative bacteria, with Enterobacter aerogenes,
      Pseudomonas aeruginosa and Hemophilus influenza occupying the first 3 places. The
      detectable rate of multiple drug resistance bacteria in postoperative group was
      much higher than preoperative groups, in which gram negative bacteria was the
      most, especially for Pseudomonas aeruginosa. There was significant difference in
      beta-lactamase detectable rate of the bacteria isolated from the delayed recovery
      group and the preoperative group (chi2 = 4.85, P < 0.05), Enterobacteriaceae
      occupied the first place among the beta-lactamase detectable bacteria isolated
      from the delayed recovery group. There was no significant difference in
      detectable rate of kinds of bacteria isolated from recovery group and control
      group. CONCLUSIONS: The main pathogens of patients with chronic rhinosinusitis
      are multiple drug resistance gram negative bacteria after operation, in which
      Pseudomonas aeruginosa occupies the first place. Gram negative bacteria are
      becoming the main opportunity pathogenic bacteria, which shows antibiotic
      resistance. microbial population of postoperative cavity from recovery group are
      becoming balanced.

PMID- 18335748
TI  - [Relationship of lingual region upper airway stricture and lingua-palate position
      type in obstructive sleep apnea hypopnea syndrome patients].
AB  - OBJECTIVE: To explore the relationship ol lingual region upper airway stricture
      and lingua-palate position type in obstructive sleep apnea hypopnea syndrome
      (OSAHS) patients. METHODS: One hundred patients with OSAHS were included in the
      study and divided into 4 groups by lingua-palate age, AHI, BMI and lowest SaO2,
      the dimensions and area of lingual region airway, the thickness of
      retropharyngeal and lateral pharyngeal tissue, the tongue width, tongue length
      and tongue area were compared among four groups. The multinomial step regression
      process was performed with SPSS software to explore the effects of lingua-palate
      position type on lingual region upper airway stricture. RESULTS: There were no
      statistical difference of age, BMI, AHI and lowest pulse oxygen among four groups
      OSAHS patients (P > 0.05). And the CT results showed: starting from type I to
      type IV, the area, coronal and arrowe diameter of lingual region upper airways
      were decreasing, tongue length, tongue area and the percentage of lingual region
      airway stricture were increasing, the percentage of lingual region airway
      stricture were 0/25, 3/39, 7/22, 14/14, respectively (P < 0.05). The multinomial
      step regression analysis showed that the area of lingual airway was the most
      important factor of lingua-palate position type, the unstandardized coefficient
      was -0.39, and standardized coefficient was -0.545. CONCLUSIONS: The study
      suggests that there is evident correlation between lingual region airway
      stricture and lingua-palate position type, and lingual region airway stricture
      can be roughly determined by lingua-palate position type.

PMID- 18335749
TI  - [Level VI and II-V cervical lymph node metastasis in differentiated thyroid
      carcinoma].
AB  - OBJECTIVE: To explore the characters of the cervical lymph node metastasis in
      differentiated thyroid carcinoma, and to provide evidence for proper surgery of
      differentiated thyroid carcinoma. METHODS: From 1984 to 2000, 99 cases with
      differentiated thyroid carcinoma were performed thyroidectomy and neck
      dissection. The patients were followed up. A retrospective analysis was
      performed. Results In 99 cases with differentiated thyroid carcinoma, there were
      61 papillary carcinoma, 13 papillary and follicular mixed carcinoma, 25
      follicular carcinoma. According to 2002 UICC TNM classification, 60 cases were
      staged I, 1 case staged II, 5 cases staged III, 33 cases staged IV. Lobectomy and
      isthmectomy was performed in 80 cases, lobectomy was resected and opposite
      subtotal lobectomy in 15 cases, total thyroidectomy in 4 cases. One hundred and
      four neck dissection were performed in 99 cases (5 cases were bilateral neck
      dissection ). Among them, 66 (68 sides) were radical neck dissection, 33 (36
      sides) were modified neck dissection. Pathological results showed that lymph
      nodes were positive in 86 sides of 83 cases. The rate of cervical lymph node
      metastasis was 83.8% (83/99). The positive rates of lymph node were 37.5%
      (39/104) in level VI and 76.9% (80/104) in II-V, which was statistically
      different (chi2 = 33.01, P < 0.01). The cervical lymph node metastasis in lateral
      area (level II-V) and that in VI had not relationship (chi2 = 2.08, P > 0.05).
      Ten and 15 year survival rates of all 99 cases were 88.3% and 84.5% respectively.
      CONCLUSIONS: The occurrence of lymph node metastasis in level VI and level II was
      different and no relationship .One can not judge whether lateral neck metastasis
      by the lymph node statue in level VI only . Although they all had good prognosis,
      patients with positive nodes in level VI were not worse than that in lateral neck
      (II-V).

PMID- 18335750
TI  - [Endoscopic thyroidectomy via chest and breasts approach in 500 cases].
AB  - OBJECTIVE: To discuss the method, the safety, the advantages and disadvantages of
      endoscopic thyroidectomy via chest and breasts. METHODS: From Mar. 2002 to Dec.
      2006, endoscopic thyroidectomy via anterior chest and breast approach was
      performed in 500 patients, including 76 cases of Grave's disease (1 case had an
      opened operation history), 111 cases of thyroid adenoma, 291 cases of nodular
      goiter (10 cases have 1-2 opened thyroidectomy history, 2 cases secondary of
      hyperthyroidism), and 22 cases of thyroid carcinoma. RESULTS: The endoscopic
      thyroidectomy was successfully carried out in 492 cases, including tumor
      enucleation in 50 cases, partial lobectomy in 210 cases, subtotal thyroidectomy
      in 212 cases (including 73 cases of Graves' disease), and lobectomy in 16 cases
      of thyroid carcinoma. The operative time length ranged from 40 to 270 min (mean
      74.5 min). Mean operative blood loss was 5.5 ml (3-250 ml), no cases underwent
      blood transfusion. The drainage was taken out in the second or third days
      postoperatively. Postoperative hospital stay ranged from 3 to 8 days (mean 4.2
      days). There were some complications including subcutaneous bleeding (3 cases),
      burn of the epidermal (1 case), inflammation of the incision (2 cases),
      subcutaneous bruising (3 cases), subcutaneous effusion (6 cases), thyroid crisis
      (1 case), and temporarily hoarseness of 2 cases. There were no complications such
      as permanence damage to recurrent laryngeal nerve or parathyroid glands. The
      complication rate was 3.6% (18/492). The hospital charges ranged from 7600 to
      13,500 RM yuan. The average cost of endoscopic thyroidectomy was 10,510 RM yuan,
      in contrast to 5700 RM yuan for the open thyroidectomy patients. The post
      operative following-up was 3 to 57 months (mean 27 months). All the patients were
      satisfied with the cosmetic results and the same curative effects as conventional
      surgery were obtained. However, 3 cases of nodular goiter, 1 case of thyroid
      carcinoma, and 1 case of Grave's disease were recurrence. The operations were
      converted into open surgery in 8 cases. The 22 cases with carcinoma were survival
      until now. CONCLUSIONS: Endoscopic thyroidectomy is a safe and effective method
      of thyroid surgery. Since all the minimal incisions are on concealed parts of the
      body, the obvious cosmetic effect of this method is guaranteed. Some
      disadvantages such as complications and more costs are needed to be improve.

PMID- 18335751
TI  - [Duration-tuning of the neurons in the inferior colliculus of guinea pigs and the
      role of gamma-aminobutyric acid mediated inhibition].
AB  - OBJECTIVE: To evaluate duration tuning in the inferior colliculus (IC) of guinea
      pigs and the role of GABA-mediated inhibition on this tuning. METHODS: Totally 23
      healthy albino guinea pigs of either sex were employed in this study. After
      anesthesia, spikes of neurons in inferior colliculus were recorded using five
      barrel glass-pipettes. The characteristic frequency was determined by recording
      iso-intensity response curves at moderate intensity level (40-70 dB SPL) and
      duration tuning was measured with signals of fixed intensity and varied
      durations. GABA-A receptor antagonist, bicuculline, was applied to neurons by
      means of in vivo micro-iontophoresis through one channel in the five-barrel glass
      pipettes. RESULTS: IC neurons of guinea pigs, especially for those who showed
      sustained temporal response pattern, showed stronger duration tuning in their
      transient response peak to signal onset. Among 207 neurons recorded, totally 93
      neurons were found to show clear duration selectivity. The duration selectivity
      was eliminated or turned to be weaker in most of the neurons in which the effect
      of bicuculline was observed successfully. CONCLUSIONS: Unlike what was reported
      in bats, duration selectivity may be a transient process for most of IC neurons
      in guinea pigs. Duration selectively of IC neurons in the guinea pig was also
      largely dependent on the GABAergic inhibition.

PMID- 18335752
TI  - [Gene rearrangement analysis of papillary thyroid carcinoma].
AB  - OBJECTIVE: To investigate the characteristics of RET/PTC and H47PTEN
      rearrangement and the association between gene rearrangement and
      clinicopathological properties of thyroid carcinoma. METHODS: Rearrangement of
      RET/PTC-1, RET/PTC-2, RET/PTC-3, ELKS-RET and H4-PTEN (H4/PTEN and PTEN/H4) was
      analyzed in 139 thyroid tumor tissues by using RT-PCR and sequencing. RESULTS:
      Twelve RET/PTC-1, 6 RET/PTC-3, 6 H4/PTEN and 7 PTEN/H4 were detected in 126
      papillary thyroid carcinomas. In 3 cases, both RET/PTC and H4-PTEN were
      identified simultaneously. However, repeated experiments did not give the same
      results of H4-PTEN rearrangement. The overall frequency of rearrangement was
      21.4% (27/126). The patients with gene rearrangement were younger (P = 0.02) and
      had a higher frequency of lymph node involvement (P = 0.02). High frequency of
      lateral neck lymph node involvement was detected in RET/PTC positive PTC (P <
      0.01). PTEN/H4 rearrangement could also be detected in medullary thyroid
      carcinoma (2/5). CONCLUSIONS: H4-PTEN rearrangement can occur simultaneously with
      RET/PTC rearrangement in PTC. High predisposition to gene rearrangement is a
      characteristic of PTC. The patients of PTC with gene rearrangement are younger
      and have a higher frequency of lymph node involvement.

PMID- 18335754
TI  - [A case of foreign bodies in parapharyngeal space].

PMID- 18335753
TI  - [Identification of tumor-associated proteins in laryngeal squamous cell carcinoma
      by proteomics].
AB  - OBJECTIVE: To establish two-dimensional electrophoresis profiles from human
      laryngeal squamous cell carcinoma tissue and paired normal tumor-adjacent mucosa
      epithelia tissue, and to identify differential expression proteins. METHODS: The
      total proteins of human laryngeal squamous carcinoma tissue and paired normal
      tumor-adjacent mucosa epithelia tissue were separated by immobilized pH gradient
      based two-dimensional gel electrophoresis (2-DE). The differential expression
      proteins were analyzed using image analysis software, then identified using mass
      spectrometry and database searching. RESULTS: Well-resolved, reproducible 2-DE
      patterns of laryngeal squamous cell carcinoma and adjacent normal mucosa
      epithelial were obtained. Differential protein spots were defined as spots in 2
      DE gels. Thirteen proteins were preliminarily identified, naming which 10
      proteins were upregulated in laryngeal cancer tissue. Such as cofilin-1, nuclear
      body protein SP140, GRP94, HSP 90, GSTP1-1, superoxide dismutase [Mn],
      cyclophilin A, proteasome activator complex subunit 2, apolipoprotein A-I
      precursor, CaM-like protein and so on. There were 3 proteins downregulated in
      laryngeal cancer tissue, which were fatty acid-binding protein, calgranulin A and
      calgranulin B. CONCLUSIONS: Thirteen proteins which are associated with the
      tumorigenesis of the laryngeal squamous cell carcinoma were characterized. These
      extensive protein variations indicate that multiple protein molecules should be
      simultaneously targeted as an effective strategy to counter the disease. It is
      better for understanding of the oncogenesis and pathogenesis in a global way,
      which in turn is a basis-for the rational designs of diagnostic and therapeutic
      methods.

PMID- 18335755
TI  - [Experimental study of baculovirus-mediated transfection of spiral ganglion cells
      in rats].
AB  - OBJECTIVE: To study the feasibility and the characteristics of recombinant
      baculovirus as spiral ganglion cells (SGC) gene transfer vector. METHODS: After
      the generation of baculovirus- green fluorescent protein( Bac-GFP) according to
      Bac-to-Bac baculovirus expression system, SGC were infected by Bac-GFP with
      different multiplicities of infection (MOI) and different concentrations of
      sodium butyrate. The transfection cell rate and mean fluorescence strength (MFS)
      were detected by fluorescence microscopy and flow cytometry. Toxicity effects of
      recombinant baculovirus vectors and sodium butyrate on SGC were determined by
      spectroscopic measurement of 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5
      diphenytetrazoliumromide (MTF). RESULTS: Baculovirus was able to infect primary
      SGC cultures. The dose-response characteristics of Bac-GFP were determined on
      SGC, and the expression level could be up-regulated by sodium butyrate. Infection
      with Bac-GFP in the absence or presence of sodium butyrate (< or =10 mmol/L) was
      considered to be non-cytotoxic to primary SGC. GFP had been expressed in SGC at 6
      h post-infection and the highest numbers of cells expressing GFP were observed at
      approximately 48 h post-infection. CONCLUSIONS: Baculovirus is a novel and
      promising tool for gene transferring into the cochlear nervous system both for
      studies of the function of foreign genes and the development of gene therapy
      strategies.

PMID- 18335756
TI  - [Diagnostic value in canalis nasolacrimalis fracture of multi-slice CT].

PMID- 18335757
TI  - [Expression of cystathionine gamma-lyase in cochlear spinal modiolar artery of
      rats].

PMID- 18335758
TI  - [Surgical repair of secondary local defect after auricular reconstruction].

PMID- 18335759
TI  - [Infantile pulmonary alveolar proteinosis: a case report].

PMID- 18335760
TI  - [Transnasal-transsphenoidal endoscopic surgery of craniopharyngioma].

PMID- 18335761
TI  - [Three cases with tuberculosis of thyroid gland].

PMID- 18335762
TI  - [A patient with secretory otitis media treated with cochlear implant and canal
      wall removal and reconstruction].

PMID- 18335763
TI  - [Summary of the second conference of members of the eighth Editorial Board of
      Chinese Journal of Otorhinolaryngology Head and Neck Surgery].

PMID- 18335764
TI  - [Contemporary treatment for recurrent respiratory papillomatosis].

PMID- 18335765
TI  - [Clinical application of surgical approach and operation space establishment in
      neck endoscopy].

PMID- 18335766
TI  - [Diagnosis and treatment of differentiated thyroid carcinoma].

PMID- 18335768
TI  - Quality reporting. Reducing the nurse burden.

PMID- 18335767
TI  - HFMA peer review. An essential tool for quality assessment.

PMID- 18335769
TI  - Creating a successful CNO-CFO partnership.

PMID- 18335770
TI  - Healthcare system-owned collection agencies.

PMID- 18335771
TI  - Increasing downstream revenue and market vis with spine centers.

PMID- 18335772
TI  - Focused financing breathes new life into aging CAH.

PMID- 18335774
TI  - Adopting supply chain best practices from across the industry.

PMID- 18335773
TI  - And now, for the million-dollar question. How much can we afford to spend?

PMID- 18335775
TI  - Vendor listing.

PMID- 18335776
TI  - Pumping up the workout. New routines are putting fun into being fit.

PMID- 18335777
TI  - From scandal to stardom: how Merck healed itself.

PMID- 18335778
TI  - Healthcare reform.

PMID- 18335779
TI  - Pharmacological thromboembolic prophylaxis for medical patients in a tertiary
      care, teaching community hospital: room for improvement.
AB  - Venous Thrombembolism (VTE) is a potentially lethal complication in hospitalized
      patients. Studies indicate that pharmacological prophylaxis may reduce the
      incidence of VTE. However, the use of VTE prophylaxis remains unclear. We aimed
      to retrospectively assess whether medically ill hospitalized patients with
      established risk factors receive pharmacological VTE prophylaxis in our 912-bed
      community-based tertiary care teaching hospital between 1997 and 2003. We
      randomly selected a sample of 350 medically ill (non surgical) hospitalized
      patients with risk factors for VTE. A total of 164 of 321 patients (51.1%)
      received pharmacological VTE prophylaxis. Patients with a platelet count of
      greater than or equal to 278 K/cu mm, a weight of 146 to 184 lbs, or a weight >
      or = 185 lbs were found more likely to receive prophylaxis. Patients with cancer
      as well as other diagnoses (compared to MI patients) were less likely to receive
      prophylaxis. We conclude that there continues to be a significant
      underutilization of VTE prophylaxis in this patient population. Strategies for
      identifying patients at risk for VTE and implementing appropriate protocols to
      ensure that these patients receive prophylaxis are necessary.

PMID- 18335780
TI  - Ureteropelvic junction obstruction in association with autosomal dominant
      polycystic kidney disease: a case report in a trauma patient.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is a common cause of cystic
      renal disease and can predispose to renal insufficiency. Although typically
      diagnosed and discussed in the pediatric population, ureteropelvic junction
      obstruction may also make patients prone to renal dysfunction and failure. These
      two disease processes can coexist in the same patient, which may, in turn,
      complicate their management. We present the case of an adult patient with known
      ADPKD who suffered a traumatic fall and subsequent retroperitoneal bleed, and was
      also diagnosed with a UPJ obstruction of the left kidney on the basis of
      pathological analysis of the specimen at the time of nephrectomy.

PMID- 18335781
TI  - Percutaneous transfemoral endovascular repair of popliteal artery aneurysms.
AB  - Popliteal artery aneurysms are the hallmark of peripheral aneurysms, accounting
      for 70%, and are commonly bilateral in 50% to 75% of patients. The prevalence and
      incidence of popliteal artery aneurysms are not precisely known. The presence of
      a popliteal aneurysm is a marker of risk to limb and life because 33% to 43% are
      associated with an abdominal aortic aneurysm. Ligation and bypass reconstruction
      has long been the "gold standard" for the treatment of popliteal aneurysms.
      Recently, endoluminal repair with a percutaneously delivered stent-graft has
      become a valid alternative to open repair. In this study, we illustrate two cases
      of a total of four patients with popliteal artery aneurysms treated with
      percutaneous stent graft placement and discuss overall management of these
      aneurysms. The other two patients had a successful early outcome (30 days), but
      long-term follow-up is still lacking.

PMID- 18335782
TI  - Surgical rescue and restoration of renal function in an anuric renal failure
      patient: a case report.
AB  - We present a case of anuric renal failure in a forty-nine year old woman
      secondary to bilateral renal artery occlusion that responded favorably to
      surgical revascularization. The patient presented with a three day history of
      diminished to absent urine output. The patient's BUN and creatinine were 52 mg/dL
      and 9.3 mg/dL, respectively. The patient remained anuric and required
      hemodialysis. Chronic atherosclerotic occlusion of both renal arteries with
      reconstitution of the renal arteries via collateral support was seen on
      angiography. Twenty-six days after presentation, the patient had aortorenal
      artery bypass using a saphenous vein graft. Postoperatively the patient had
      excellent diuresis with the creatinine improving to a nadir of 1.5 mg/dL. This
      case is a demonstration that the kidneys can remain viable with subacute renal
      artery occlusion in the presence of adequate collateral blood flow. Surgical or
      transcatheter renal revascularization should be considered in appropriate
      patients.

PMID- 18335783
TI  - Adult diagnosed Dandy Walker malformation presenting as an acute brainstem event-
      a case report and review of the literature.
AB  - The Dandy Walker Malformation (DWM) is an infrequent condition seen in pediatric
      patients. Adult presentation of DWM is extremely rare. This condition usually
      presents in childhood with hydrocephalus and cerebellar signs and symptoms. This
      case describes a woman with an undiagnosed DWM who was asymptomatic until the age
      of 56 when she developed the acute onset of headache, nausea, vomiting, and
      diplopia. Her history and physical exam were consistent with an acute brainstem
      infarct. MRI revealed the underlying malformation. The clinical and radiological
      findings are discussed as well as their implications and possible etiologies.

PMID- 18335784
TI  - The physician as public health officer.

PMID- 18335785
TI  - A vibrant, healing environment.

PMID- 18335786
TI  - Changes on the horizon. How the latest government measures affect the mobility
      industry.

PMID- 18335787
TI  - When wounds are hard to heal. The challenge of treating chronic wounds.

PMID- 18335788
TI  - Facility-based equipment and capital expenditures. 2008 a roundtable. Decision
      makers discuss their purchasing strategies.

PMID- 18335789
TI  - Diathermy: comeback, or new technology? An electrically induced therapy modality
      enjoys a resurgence.

PMID- 18335790
TI  - RightSizing. Maintaining a fluid practice--despite the next reorganization.

PMID- 18335791
TI  - CMS implements severity-based DRG system for 2008. Medicare issues a new
      diagnosis-based tier to coding system.

PMID- 18335792
TI  - Molecular profiling of tumours by immunohistochemistry.

PMID- 18335793
TI  - Spectrum of histological features in non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has become an Important
      entity globally, including in India and other Asian countries. Morphological
      evaluation of a liver biopsy is necessary for the diagnosis, staging and possibly
      management of this disease. However, the spectrum of changes in the liver, their
      evolution, Interrelationships and implications are incompletely understood. We
      aimed to study the spectrum of histological abnormalities in NAFLD. METHODS: The
      study material was drawn from a pool of 80 liver biopsies diagnosed in our
      laboratory as NAFLD, 67 retrieved retrospectively from our records and 13
      obtained prospectively with complete clinical data. After comprehensive
      histological assessment, a detailed analysis was done of 32 of those categorized
      as definitive NAFLD on the basis of a dependable history of no alcohol Intake and
      seronegativity for hepatitis virus B and C Infections. RESULTS: Fatty change was
      preferentially seen in acinar zones 2 and 3, more so in the former. Steatotic
      cells varied in size; some large ones were non-spherical. Steatosis alone was
      present in more than a quarter of the cases and steatosis along with inflammation
      was present in half. The magnitude of steatosis correlated with inflammation,
      while both these seemed to correlate with hepatocyte Injury and fibrosis.
      CONCLUSION: A proportion of patients with NAFLD show only hepatic steatosis. An
      Increasing grade of steatosis is associated with greater Inflammation, hepatocyte
      injury and acinar fibrosis. Preferential involvement of acinar zone 2 by
      steatosis, the morphology of the steatotic cells, and nature and location of
      inflammation are important in the diagnosis of NAFLD and its differentiation from
      other causes of fatty liver.

PMID- 18335794
TI  - Obesity in Indian children: time trends and relationship with hypertension.
AB  - BACKGROUND: Limited data are available from India regarding the distribution and
      profile of childhood obesity and hypertension. We examined the time trends in
      childhood obesity in a representative sample of schoolchildren from Ernakulam
      District, Kerala and determined the relationship of obesity with blood pressure.
      METHODS: We used a stratified random cluster sampling method to select the
      children. Anthropometric data were collected from 24 842 students, 5-16 years of
      age, during 2003-04. Blood pressure and anthropometric data were collected from
      20 263 students during 2005-06. Overweight and obesity were defined by body mass
      index for gender and age. Gender, age and height were considered for determining
      hypertension. RESULTS: The proportion of overweight children increased from 4.94%
      of the total students in 2003 to 6.57% in 2005 (OR: 1.36; 95% CI: 1.25-1.47; p <
      0.0001). The increase was significant in both boys and girls. The proportion of
      overweight children was significantly higher in urban regions and in private
      schools, and the rising trend was limited to private schools. Systolic or
      diastolic incident hypertension was found in 17.34% of overweight children versus
      10.1% of the remaining students (OR: 1.87; 95% CI: 1.60-2.17; p < 0.0001).
      CONCLUSION: Childhood obesity showed an increasing trend in a short period of 2
      years. Hypertension was common in overweight children. The results suggest the
      need for greater public awareness and prevention programmes on childhood obesity
      and hypertension.

PMID- 18335795
TI  - Are we really making motherhood safe? A study of provision of iron supplements
      and emergency obstetric care in rural Maharashtra.
AB  - BACKGROUND: The Government of India launched the National Rural Health Mission
      (NRHM) in 2005 to improve healthcare delivery and strengthen the public health
      system. Prevention and management of anaemia during pregnancy and access to
      quality emergency obstetric care services are important factors in reducing
      maternal mortality, which is a priority goal in the NRHM. We studied the ground
      realities specific to the availability of maternity services in the public health
      system of Maharashtra. METHODS: The study was done in the rural areas of
      Ahmednagar district in Maharashtra in 2006. Data regarding the number and place
      of deliveries, and details regarding iron supplements received and used were
      collected from 14 primary health centres selected by a stratified random method.
      Data regarding the number of caesarean section operations conducted in 3 selected
      rural hospitals and the availability of iron supplements at the district
      headquarters were also obtained. Three questionnaires were used in the format
      prescribed under the Right to Information Act of the Government of India, 2005.
      RESULTS: No iron supplement was available during the entire year in 21% of
      primary health centres. Iron supplements were available for 1-4 months, 5-8
      months and 9-11 months, in 4, 3 and 4 primary health centres, respectively. The
      district headquarters did not receive supplies of iron supplements during the
      year from higher authorities. No caesarean sections were done in any of the
      selected rural hospitals during 2006. The proportion of deliveries that took
      place in primary health centres and subcentres, at home, and at private
      healthcare facilities was 1:1.5:5. CONCLUSION: Essential supplies such as iron
      supplements are in short supply and emergency obstetric care services are
      nonexistent in the public health system in our study area. The NRHM needs to
      address the ground realities to make motherhood safe.

PMID- 18335796
TI  - Renal thrombotic microangiopathy and cerebral venous thrombosis in a young man.
AB  - We report a patient of primary catastrophic antiphospholipid syndrome who
      presented with rapidly progressive renal failure and seizures. He was detected to
      have thrombotic microangiopathy on kidney biopsy and deep cerebral venous
      thrombosis. The patient was successfully managed with anticoagulants, steroids,
      plasmapheresis and cyclophosphamide.

PMID- 18335797
TI  - Newly diagnosed multiple myeloma: allograft or autograft?

PMID- 18335798
TI  - Hepatitis A vaccine versus immunoglobulin for post-exposure prophylaxis.

PMID- 18335799
TI  - Treatment of diabetes mellitus: beyond glycaemic control.

PMID- 18335800
TI  - Health information management: an introduction to disease classification and
      coding.
AB  - Morbidity and mortality data constitute an important component of a health
      information system and their coding enables uniform data collation and analysis
      as well as meaningful comparisons between regions or countries. Strengthening the
      recording and reporting systems for health monitoring is a basic requirement for
      an efficient health information management system. Increased advocacy for and
      awareness of a uniform coding system together with adequate capacity building of
      physicians, coders and other allied health and information technology personnel
      would pave the way for a valid and reliable health information management system
      in India. The core requirements for the implementation of disease coding are: (i)
      support from national/institutional health administrators, (ii) widespread
      availability of the ICD-10 material for morbidity and mortality coding; (iii)
      enhanced human and financial resources; and (iv) optimal use of informatics. We
      describe the methodology of a disease classification and codification system as
      also its applications for developing and maintaining an effective health
      information management system for India.

PMID- 18335801
TI  - Non-payment of private hospital bills of dying patients.

PMID- 18335802
TI  - A Federal election is due before the end of 2007.

PMID- 18335803
TI  - Rising trend of non-communicable diseases in low socioeconomic areas.

PMID- 18335804
TI  - Medical education in India: the way forward.

PMID- 18335805
TI  - Newer insights into renal regulation of water homeostasis.
AB  - The regulation of high osmolality is an important driving force for water
      reabsorption and urinary concentration--the key functions of the kidney for
      maintaining optimum body fluid volume. New evidence shows that transcription
      factor tonicity responsive enhancer binding protein (TonEBP) and calcineurin
      nuclear factor of activated T cells through cross-talk enhance Aquaporin 2 (AQP2)
      expression. AQP2 is the predominant vasopressin regulated water channel of the
      kidney collecting duct and is essential for urinary concentration. The
      serine/threonine phosphatase calcineurin is an important signaling molecule
      involved in kidney development and function. One potential target of calcineurin
      action is the water channel AQP2. The nuclear factor of activated T cells (NFAT)
      family has recently been expanded by the discovery of a new member, NFAT 5, or
      Ton EBP. Ton EBP is the only known mammalian transcription factor that regulates
      gene expression in response to hypertonicity. This review examines the importance
      of AQP2, calcineurin, NFATc and TonEBP in the renal regulation of water
      homeostasis.

PMID- 18335806
TI  - Detection of anti-Haemonchus contortus antibodies in sheep by dot-ELISA with
      immunoaffinity purified fraction of ES antigen during prepatency.
AB  - Haemonchosis is a very common disease in small ruminants caused by H. contortus,
      a blood sucking parasite causing anaemia that may be fatal particularly to young
      animals. Therefore, detection of the infection during prepatent period is
      important for early treatment. Excretory-Secretory (ES) protein of H. contortus
      was purified through immunoaffinity chromatography. Dot -ELISA was performed with
      crude ES antigen as well as immunoaffinity purified fraction (F-1) with
      experimental and natural sera of sheep infected with H. contortus. Solid dot
      formation took place with 4 day, 1, 2 and 3 weeks post infection sera. Dot
      formation did not take place with negative control serum and uninfected control
      animal serum. When crude ES antigens was reacted to natural sheep sera having H.
      contortus infection, 60% sera samples showed solid dot formation whereas in F-1
      fraction 75% of the sera samples showed solid dot indicating purified fraction
      was a more potent antigen. Crude ES and F-1 were also fractionated through SDS
      PAGE. ES antigen revealed polypeptides in the range of 10 to 200 kDa of which 26,
      32, 60 and 120 kDa were found more prominent. F-1 fraction on SDS-PAGE analysis
      revealed only four polypeptides of 26, 32, 60, and 120 of which 60 and 120 kDa
      were found to be most prominent. Results indicate that the purified fraction of
      ES antigen may be utilized for early diagnosis of haemonchosis. Further studies
      on cross antigenicity of this fraction with other nematode and trematode needs to
      be conducted.

PMID- 18335807
TI  - Pathological studies on Bovine papilloma virus-fern interaction in hamsters.
AB  - Early pathological changes of Bovine papilloma virus (BPV-2)-fern (Pteridium
      aquilinum and Onychium contiguum fern) interaction in hamsters were studied. In
      bracken-exposed cattle, BPV induces malignancy in gastrointestinal and urinary
      bladder mucosa. Cutaneous warts were transmitted successfully in hamsters
      approximately after 3 months post inoculation while urinary bladder tumour of
      enzootic bovine haematuria cases were not transmitted. Histologically, tumour was
      diagnosed as fibroma. Onychium produced more pronounced effects than bracken fern
      which was characterized by significant reduction in body weight and testicular
      atrophy. BPV-fern interaction was not appreciable during early period of tumour
      induction and requires long-term studies for 12 to 18 months.

PMID- 18335808
TI  - Lycopene ameliorates thermal hyperalgesia and cold allodynia in STZ-induced
      diabetic rat.
AB  - Peripheral neuropathy is one of the common complications of diabetes mellitus. It
      is frequently associated with debilitating pain. The present study was designed
      to investigate effect of Lycopene, a carotenoid found in tomatoes, on
      hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats.
      After 4-weeks of STZ injection, diabetic mice exhibited a significant thermal
      hyperalgesia cold allodynia, hyperglycemia and loss of body weights as compared
      with control rats. Chronic treatment of lycopene for 4 weeks significantly
      attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the
      role of antioxidant such as lycopene as an adjuvant therapy in the treatment of
      diabetic neuropathy.

PMID- 18335809
TI  - Efficiency of propolis extract against mitochondrial stress induced by
      antineoplasic agents (doxorubicin and vinblastin) in rats.
AB  - To assess the oxidative stress and mitochondrial dysfunction associated with
      disease, toxic process and aging, in vivo and in vitro preventive effect of
      propolis extract against mitochondrial oxidative stress induced by two anticancer
      drugs (doxorubicin and vinblastin) have been investigated in female wistar rat
      using liver and heart mitochondria. The results show that doxorubicin and
      vinblastin altered mitochondrial functions as observed by a decrease in
      respiratory control value, an activation of swelling and overproduction of
      superoxide anion. Myocardial tissue from doxorubicin treated rats showed a marked
      increase in malondialdehyde production, a depletion of reduced glutathione
      contents and an inhibition of catalase and superoxide dismutase activities.
      Similar results were also observed in liver tissue. Pretreatment of rats with
      propolis extract (100 mg/kg/day po) (10(-4) M ip) administered 4 days prior to
      doxorubicin (20 mg/kg) and/or vinblastin (2 mg/kg) injection, substantially
      reduced the peroxidative damage in myocardium and hepatic tissues and markedly
      restored the tissues catalase and SOD activities. The results strongly suggest
      that propolis extract protects heart and liver tissues from oxidative stress by
      protecting the mitochondria.

PMID- 18335810
TI  - In vitro antiviral activity of plant extracts on goatpox virus replication.
AB  - Four plants having known medicinal properties were screened for inhibition of
      goatpox virus (GTPV) replication in vitro. Of the 4 plants, extract of Acacia
      arabica (Babul) and Eugenia jambolana (Jamun) leaves had inhibition (%) 99.70 and
      99.92 at their maximum non toxic concentrations, 99.93 +/- 0.38 and 1999.73 +/-
      0.50 microg/ml, respectively in all cytopathic effect (CPE) inhibition assays.
      Inhibition of GTPV virus replication was further confirmed by PCR and SYBR Green
      based quantitative real-time QPCR assays specific for GTPV. Results indicated
      that the extract of Acacia arabica and Eugenia jambolana leaves inhibited GTPV
      replication in vitro.

PMID- 18335811
TI  - Anti-microfilarial activity of methanolic extract of Vitex negundo and Aegle
      marmelos and their phytochemical analysis.
AB  - In the present study, methanolic extracts of roots of Vitex negundo L. and
      extracts of leaves of Vitex negundo L., Ricinus communis L. and Aegle marmelos
      Corr. were explored for possible antifilarial effect against Brugia malayi
      microfilariae. It was observed that among the herbal extracts, root extract of
      Vitex negundo L. and leaves extract of Aegle marmelos Corr. at 100 ng/ml
      concentration showed complete loss of motility of microfilariae after 48 hr of
      incubation. Thin layer chromatography of the extracts revealed the presence of
      alkaloids, saponin and flavonoids in the roots of Vitex negundo L. and coumarin
      in the leaves of Aegle marmelos Corr.

PMID- 18335812
TI  - Ameliorative effect of Partysmart in rat model of alcoholic liver disease.
AB  - Present study was designed to investigate the effect of polyherbal formulation
      PartySmart in experimental model of alcoholic liver disease in male Wistar strain
      rats. Alcohol plus fish oil were administered to animals for 8 weeks to induce
      liver injury. PartySmart was administered at doses of 250 and 500 mg/kg body
      weight. After 8 weeks, parameters such as liver weight, liver function serum
      markers alanine transaminase (ALT), aspartate transaminase (AST) and alkaline
      phosphatase (ALP) and lipid peroxidation were studied. Livers from all the groups
      were subjected for histological evaluation. Treatment with PartySmart at the dose
      of 500 mg/kg body weight showed significant reduction in the levels of serum ALT,
      AST and ALP with a decrease in liver weight as compared to ethanol-fed rats. A
      significant decrease was also observed in malondialdehyde levels following
      treatment with PartySmart at 500 mg/kg body weight. Histological profile of liver
      tissue in PartySmart-treated animals showed lesser vacuolar degeneration and
      intactness of hepatic architecture along with improved glycogen deposition as
      demonstrated by PAS staining. PartySmart ameliorated alcohol-induced liver injury
      by preventing cell membrane disturbances, reduction of oxidative stress by free
      radical scavenging and antioxidant activity and normalization of altered
      intracellular redox status. Thus, PartySmart can be beneficial in the treatment
      of alcohol-induced liver damage.

PMID- 18335813
TI  - Nutritional regulation of actinomycin-D production by a new isolate of
      Streptomyces sindenensis using statistical methods.
AB  - Production of actinomycin-D, by an isolate, S. sindenensis, was optimized by
      statistical methods. Fructose peptone and NaNO3 were found to be critical for
      antibiotic production. In the second step, their concentrations were optimized
      with Central Composite Design and Response Surface Methodology. Fructose, peptone
      and NaNO3 at 2.55, 0.309 and 0.114% respectively gave approximately 261% higher
      yield (289 mg/l). Cultivation in fermentor at 600 rpm agitation and 1.5 vvm
      aeration with optimized medium gave 3.56 folds higher yield (365 mg/l) as
      compared to the yields in shake flasks using normal production medium (80 mg/l).

PMID- 18335814
TI  - Current topics in oral pathology.

PMID- 18335815
TI  - The 2007 AHA guidelines: issues and discussion concerning clinical dental
      practice.

PMID- 18335816
TI  - Tissue biomarkers for diagnosis & management of oral squamous cell carcinoma.
AB  - Squamous cell carcinoma (SCC) accounts for more than 90% of malignancies of the
      oral cavity and oropharynx. Globally, SCC is one of the top ten cancers with a
      predilection for older males. In the U.S., SCC accounts for more deaths annually
      than cervical cancer, malignant melanoma or Hodgkin's lymphoma and costs about 2
      billion dollars in treatment expenses. The 5-year survival rate is less than 50%,
      a prognosis that is poorer than that of breast cancer or melanoma.2 Significant
      numbers of patients develop local recurrence, second primary tumors and distant
      metastases. Patients presenting with late stage disease resulting in poor
      survival, are common; in part due to inadequate screening protocols and access to
      care issues. In the following review article, the risk factors, current screening
      protocols, treatment options and biomarkers for diagnosis and prognosis of SCC,
      will be discussed.

PMID- 18335817
TI  - The future of oral pathology practice.
AB  - Oral and maxillofacial pathology (OMP) may be viewed as a specialty of dentistry,
      which addresses the diagnosis and treatment of diseases of the oral and perioral
      regions. Consensus definitions may be found in the accreditation standards for
      OMP as published by the American Dental Association, and in the Constitution and
      Bylaws of the American Academy of Oral and Maxillofacial Pathology (AAOMP). These
      sources describe roles for OMP in laboratory diagnosis (histopathology), and
      clinical practice. Eversole recognizes these divisions of OMP in his discussion
      of evidence-based practice, noting that oral medicine shares with OMP
      responsibilities in the care of patients with oral disease. Broadly viewed, all
      clinical disciplines and specialties of dentistry provide services in disease
      diagnosis and treatment. However, Eversole makes a distinction between the
      diagnostic and treatment services provided throughout dentistry, and those
      offered by OMP, excluding from OMP those primarily focused on dental caries,
      diseases of the periodontium, missing teeth and tooth structure, and dental
      misalignment. The focus of this essay addresses the future of OMP practice.

PMID- 18335818
TI  - Osteonecrosis of the jaws and bisphosphonates.

PMID- 18335819
TI  - Evaluation of the dry mouth patient.
AB  - This paper examines the questions "who is the dry mouth patient and how is the
      dry mouth patient evaluated"? It reviews the clinical features of dry mouth. It
      presents current treatment options for dry mouth care.

PMID- 18335820
TI  - Expanding the activities of the D. Walter Cohen Middle East Center for Dental
      Education beyond its boundaries: Turkey and Dubai.

PMID- 18335821
TI  - Driven out by Hitler.

PMID- 18335828
TI  - [A wound, wound healing ... and many ways to achieve this].

PMID- 18335829
TI  - [Dying in the hospital].

PMID- 18335830
TI  - [Evolution of the management of dying in the hospital].

PMID- 18335831
TI  - [Dying in the hospital. Medical and legal obstacles].

PMID- 18335832
TI  - [Management of fetal and perinatal deaths].

PMID- 18335833
TI  - [Best practices in the mortuary].

PMID- 18335834
TI  - [Specimen collection has a scientific goal].

PMID- 18335835
TI  - [Corneal harvesting in heart arrest].

PMID- 18335836
TI  - [Donation of the body to science].

PMID- 18335837
TI  - [Transportation of a body without a coffin].

PMID- 18335838
TI  - [The mortuary practice profession].

PMID- 18335839
TI  - [Embalming, or the process of preserving the body].

PMID- 18335840
TI  - [Respecting funeral rites].

PMID- 18335841
TI  - [Death and caring for the family].

PMID- 18335842
TI  - [Dying in the hospital].

PMID- 18335843
TI  - [10/10 Rights and infection control hygiene].

PMID- 18335844
TI  - [9/10 The emergency crash cart].

PMID- 18335845
TI  - Some reflections on ibuprofen.

PMID- 18335846
TI  - Ibuprofen: a journey from prescription to over-the-counter use.
AB  - Ibuprofen was the first non-aspirin non-steroidal antiinflammatory drug (NSAID)
      to be approved for over-the-counter (OTC) use and is widely considered to be the
      best tolerated drug of its class. Low-dose, OTC ibuprofen has been used for pain
      relief for over 30 years without any obvious major health issues. However, there
      is no clear differentiation between the OTC and prescription doses of ibuprofen,
      and their respective effects. Adverse reactions to ibuprofen appear to be dose
      and duration dependent, and this may be the reason for the observed tolerability
      of the drug at OTC doses. OTC ibuprofen is at least as effective as aspirin and
      more effective than paracetamol. The tolerability concerns associated with higher
      dose NSAIDs currently do not apply to low-dose, short-term use of ibuprofen for
      common pain. Ibuprofen is associated with the least risk of GI complications
      compared with other NSAIDs and is considered relatively benign in overdose. This
      review will aim to distinguish the safety of OTC or non-prescription use of
      ibuprofen from its prescription use.

PMID- 18335847
TI  - Ibuprofen and cardiovascular safety: where do we stand?

PMID- 18335848
TI  - Ibuprofen and gastrointestinal safety: a dose-duration-dependent phenomenon.
AB  - In summary, scientific evidence demonstrates that the rate of serious GI adverse
      events associated with the use of NSAIDs is comparatively low depending on the
      definition used, serious GI adverse events occur in 1% of patients each year and
      occurs in the use of high doses with long-term treatment in chronic conditions.
      At OTC doses, the incidence of GI adverse events in both adults and children
      receiving ibuprofen has been shown to be similar to that of paracetamol. Even at
      prescription doses of ibuprofen, upper GI bleeding is infrequent, and is usually
      associated with long-term use. Of all the NSAIDs, ibuprofen appears to have one
      of the best GI tolerability profiles.

PMID- 18335849
TI  - Ibuprofen and asthma in paediatric populations: clinical concern or clinical
      reality?

PMID- 18335850
TI  - Use of ibuprofen in paediatric populations.

PMID- 18335851
TI  - Social movement. Pull together.

PMID- 18335852
TI  - Changing of the guards.

PMID- 18335853
TI  - The doctorate in clinical laboratory science: enhanced quality for healthcare.

PMID- 18335854
TI  - Transfusion therapy for autoimmune hemolytic anemia patients: a laboratory
      perspective.
AB  - Patients presenting with autoimmune hemolytic anemias create inherent challenges
      to those tasked with providing compatible blood for transfusion therapy. These
      patients have developed autoantibodies against their own red cell surface
      antigens. Because these antigens are usually high-incidence, these patients will
      typically demonstrate panagglutination when their serum is exposed to most
      commercially procured screening red blood cells. This makes the identification of
      clinically significant alloantibodies difficult for laboratory personnel.
      Transfusion history, patient phenotype availability, and previous antibody
      records all impact the testing methods. The end goal is to identify clinically
      significant alloantibodies in order to provide antigen negative, compatible red
      blood cells, which reduces the risk of transfusion related reactions. It is
      imperative to understand the laboratory results and the techniques available that
      guide the investigative process.

PMID- 18335855
TI  - Wake up! Your PDQ is due!

PMID- 18335856
TI  - Rheumatoid factor and anti-CCP autoantibodies in rheumatoid arthritis: a review.
AB  - For many years, laboratory diagnosis of rheumatoid arthritis has relied on the
      detection of rheumatoid factor. A new assay that detects antibodies to
      citrullinated peptides, called the anti-CCP assay, has demonstrated a comparable
      sensitivity but a much higher specificity than the RF test. This paper reviews RF
      and anti-CCP in rheumatoid arthritis and examines the usefulness of each
      autoantibody in RA testing.

PMID- 18335857
TI  - Teaching method validation in the clinical laboratory science curriculum.
AB  - With the Clinical Laboratory Improvement Amendment's (CLIA) final rule, the
      ability of the Clinical Laboratory Scientist (CLS) to perform method validation
      has become increasingly important. Knowledge of the statistical methods and
      procedures used in method validation is imperative for clinical laboratory
      scientists. However, incorporating these concepts in a CLS curriculum can be
      challenging, especially at a time of limited resources. This paper provides an
      outline of one approach to addressing these topics in lecture courses and
      integrating them in the student laboratory and the clinical practicum for direct
      application.

PMID- 18335858
TI  - A survey of quality indicator use in the clinical laboratory.
AB  - OBJECTIVE: A survey of clinical laboratories was conducted to capture information
      about quality indicators in use within the state of Arizona. This information was
      then used to determine which quality indicators are applicable across the
      spectrum of clinical laboratories making them suitable for benchmarking
      laboratory performance. The objectives of this study were also to heighten
      awareness of benchmarking practices for clinical laboratory managers and
      laboratory quality assurance personnel, to develop objective methods of quality
      monitoring for performance improvement, and to encourage collaboration between
      laboratories and accreditation agencies. METHODS: A review of the current
      literature was conducted to assess the status of benchmarking within the clinical
      laboratory. Data were also obtained from the Centers for Medicare & Medicaid
      Services (CMS) about all licensed clinical laboratories in Arizona. A mail survey
      was then created and conducted to investigate the use of clinical laboratory
      quality indicators in Arizona. SETTING AND PARTICIPANTS: A paper survey was
      mailed to a representative sample of clinical laboratory managers included in the
      CMS licensed laboratories listing for the state of Arizona. MAIN OUTCOME
      MEASURES: The selected sample was surveyed by mail and validation testing of the
      survey was conducted using the t-test. The compiled survey data is also presented
      in the form of histograms. RESULTS: Applying the t-test to the sample vs.
      population data proved that the sample was not a very good representation of the
      population and a better selection method should be used in future studies. Of the
      319 of 3198 clinical laboratories randomly selected to receive the survey, 21
      (6.58% of the sample or 0.66% of the population) responded with completed
      surveys. The information received from the respondents revealed a relationship
      between test volume and the number of indicators being monitored by clinical
      laboratories, the preference of indicators being monitored by those laboratories,
      the size of the laboratories where the majority of benchmarking is occurring, and
      a link between accrediting agencies and benchmarking activities. CONCLUSION: The
      survey proved that quality indicators are used for quality improvement purposes
      within the clinical laboratory; although it also showed that the industry still
      does not have a standardized approach to the use of quality indicators for
      benchmarking performance against other laboratories.

PMID- 18335859
TI  - Finding the knowledge in information.

PMID- 18335860
TI  - Searching MEDLINE via PubMed.
AB  - As the volume of biomedical literature has increased, so have the number and
      complexity of databases that index it. Learning to conduct an efficient
      literature search in an online database is an essential skill for today's
      clinical laboratory scientist. This article describes basic and advanced
      strategies for searching PubMed and the use of specialized features including
      MyNCBI.

PMID- 18335861
TI  - Searching the biomedical literature: research study designs and critical
      appraisal.
AB  - Two essential issues to consider when assessing the validity of research studies
      are the strengths and weaknesses of the study design and quality of methodology.
      This paper reviews study designs commonly used in clinical research, including
      case reports, cross-sectional studies, case-control studies, cohort studies,
      randomized controlled trials, reviews, and meta-analyses. It concludes with an
      outline for assessing study quality.

PMID- 18335862
TI  - A survey of scholarly literature databases for clinical laboratory science.
AB  - This article reviews the use of journal literature databases including CINAHL,
      EMBASE, and Web of Science; summarizing databases including Cochrane Database of
      Systematic Reviews, online textbooks, and clinical decision-support tools; and
      the Internet search engines Google and Google Scholar. The series closes with a
      practical example employing a cross-section of the knowledge and skills gained
      from all three articles.

PMID- 18335863
TI  - 'Something must be done'.

PMID- 18335864
TI  - Scottish review flawed.

PMID- 18335865
TI  - Breastfeeding friendly.

PMID- 18335866
TI  - An induction programme for health visitors.
AB  - Bradford South and West PCT developed a comprehensive induction programme for
      newly-qualified health visitors in order to enhance the support offered to these
      practitioners. This study examined the experiences of a group of health visitors
      who have undergone this programme and compared it with the experiences of health
      visitors who did not receive a structured induction. The data were collected by
      means of two focus groups and were analysed using framework analysis. The
      findings indicated that the induction programme was very valuable to newly
      qualified health visitors, as well as those new to the PCT. Health visitors who
      had taken part in the programme felt privileged to have had this opportunity. The
      programme helped them adjust to their new roles and made the transference to
      personal accountability easier. The provision of peer support and preceptorship
      enhanced learning and effective decision-making, and encouraged reflection. The
      health visitors who had not received a structured induction felt they had been at
      a distinct disadvantage and welcomed the new programme. There was a consensus of
      opinion that the induction programme would have a positive impact on the
      recruitment and retention of health visitors and should continue to be developed.

PMID- 18335867
TI  - Health visiting and community matrons: progress in partnership.
AB  - Since primary care services face their biggest challenges in the reorganisation
      of the NHS, a major theme for future service delivery is the effective management
      of clients with long-term conditions. Nationally, PCTs are committed to preparing
      experienced, senior nurses as community matrons, who will lead integrated health
      and social care for people with multiple long-term conditions and reduce hospital
      admissions. This paper discusses how health visitors can influence and support
      the development of local long-term condition services and the importance of
      health visitors working with community matrons to share their experiences and
      skills for the benefit of both patients and professionals.

PMID- 18335868
TI  - The expectations of families and patterns of participation in a Trailblazer Sure
      Start.
AB  - The aim of this case study was to evaluate the local impact of an innovative Sure
      Start located in the east of England. The evaluation addressed the expectations
      of parents/carers for themselves and their children, and the extent to which Sure
      Start contributed to their achievement. A distinction was made between regular
      users and families that did not engage with services. Methods included individual
      interviews, events data linkage, goal attainment scales for parents and children
      and group review with stakeholders. The participants were 67 local families (160
      individuals), all of whom had at least one child born between August 2001 and
      April 2004. An exploration of the utilisation of services over time and consumer
      engagement with services showed that the programme became more effective at
      engaging families. The role of community practitioners in the early promotion of
      Sure Start became apparent. Certain entry points, such as a home visit by a
      health visitor, were associated with more contacts, and more sustained pathways
      through the programme. Families that were actively engaged with Sure Start
      identified a range of benefits, especially greater social inclusion. The
      expectations of families who were 'active users' of Sure Start services matched
      the aims of Sure Start, and were being met.

PMID- 18335869
TI  - The Children's Plan.

PMID- 18335870
TI  - Head lice.

PMID- 18335871
TI  - CNN code of conduct.
AB  - It is important that a CNN understands their employer's local policies,
      procedures and clinical protocols. To enable a CNN to practise, they must be
      appropriately trained, have clinical supervision and work in partnership with
      others. A CNN must maintain client confidentiality, and act accordingly with all
      partnership communications. A CNN has a duty of care to themselves, the clients,
      colleagues and the employer.

PMID- 18335872
TI  - Dismay at NMC change for SCPHNs.

PMID- 18335873
TI  - Ideology of integrated working.

PMID- 18335874
TI  - New pay arrangements for working unsocial hours.

PMID- 18335875
TI  - Skin-deep cases.

PMID- 18335876
TI  - A 2-year-old boy with fever and altered mental status.

PMID- 18335877
TI  - Painful plantar papules and nodules in a child. Palmoplantar eccrine hidradenitis
      (PEH).

PMID- 18335878
TI  - A 12-year-old girl with irritated earlobes.

PMID- 18335879
TI  - One disease, multiple manifestations.

PMID- 18335880
TI  - A 17-month infant with a calf lesion and generalized hypotonia.

PMID- 18335881
TI  - Alternatives for fragrance-allergic children.
AB  - In 2007 "fragrances" were named "allergen of the year" by the American Contact
      Dermatitis Society to highlight the importance of this group of allergens.
      Because fragrance allergy in children is a real problem that is potentially
      avoidable by substituting products free of these sensitizing chemicals (see
      Table, page 103), action toward awareness and prevention is imperative.

PMID- 18335882
TI  - Avoiding paraphenylenediamine exposure in children.
AB  - Although the allergenic potential of PPD is well known, it was chosen by the
      American Contact Dermatitis Society as the 2006 "allergen of the year" in order
      to increase awareness of new patterns of exposure and increasing sensitization.
      Temporary tattoos are a vehicle of contact with PPD that is particularly relevant
      to children. They are a risk not only in the United States, but in many
      international locations frequented by American tourist families. Adolescents
      dyeing their hair are also at risk. With this in mind, measures should be taken
      to increase awareness and avoid the unnecessary usage of PPD in children.

PMID- 18335883
TI  - [Anti-TNF agents, the class of drugs that promotes treatment for Crohn disease].

PMID- 18335884
TI  - [Acid related diseases progress in 2007].
AB  - The treatment of reflux disease did not changed. PPI treatment remains the first
      line treatment and surgery a second line treatment. The effect of surgery in
      reflux disease reduces and, after ten years, a part of the operated patients
      needs PPI again. The triple therapy is the treatment of choice of Helicobacter
      pylori infection. Patients with persistent Helicobacter pylori infection, after a
      first treatment, should be treated with a sequential treatment. PPI are effective
      in the prevention of gastroduodenal lesions and in the treatment of dyspeptic
      symptoms during NSAID treatment. IPP should be given to all patients presenting
      dyspeptic symptoms under NSAID or COX-2 administration.

PMID- 18335885
TI  - [Main therapeutic advances in IBD in 2007].
AB  - In 2008 three biological agents against TNFalpha will be available. The
      combination of infliximab with azathioprine is no longer recommended, as
      hepatosplenic lymphomas with a particularly bad prognosis have been associated
      with this combined therapy. Regular maintenance therapy with infliximab is as
      effective in preventing the development of anti-infliximab antibodies as co
      administration of this anti-TNFalpha agent with an immunomodulator. The benefit
      of regular maintenance therapy is probably linked to the presence of residual
      trough levels of infliximab between perfusions.

PMID- 18335886
TI  - [Highlights in hepatology].
AB  - This review highlights new treatment options in chronic hepatitis B, issues
      related to antiviral resistance and current recommendations for the monitoring of
      patients on treatment. We also discuss post-exposure prophylaxis of hepatitis A,
      treatment duration in chronic hepatitis C and recent studies exploring
      vaccination against hepatitis E and pioglitazone for nonalcoholic
      steatohepatitis. Finally, we will briefly comment new findings in alcoholic
      hepatitis as well as acetaminophen hepatotoxicity and summarize revised criteria
      for the diagnosis and management of hepatorenal syndrome.

PMID- 18335887
TI  - [Liver transplantation: new organ allocation system in Switzerland].
AB  - This article describes the new organ allocation system for liver transplantation
      introduced in Switzerland on July 1, 2007. In its newly adopted transplantation
      law, Switzerland chose the MELD score (Model for end-stage liver disease), based
      on three laboratory values: total bilirubin, serum creatinine and INR. Advantages
      and limitations of the MELD score are discussed. Finally the West Switzerland
      joint liver transplantation program is briefly introduced.

PMID- 18335888
TI  - [Colorectal cancer screening: follow-up of patients with adenomatous and
      colorectal cancer].
AB  - The different methods of colorectal cancer screening are discussed. Our
      recommendations had not changed: we recommend as colorectal cancer screening a
      colonoscopy at the age of 50 years in all healthy persons with average risk for
      colorectal cancer. A 2007 interdisciplinary consensus conference revised the
      Swiss recommendations for the follow-up of patients with operated colorectal
      cancer or after polypectomy.

PMID- 18335889
TI  - [Surgery].
AB  - 2007 was marked by a growing trend towards minimal invasive surgery and enhanced
      recovery, especially in visceral surgery. In comparison to the laparoscopic
      revolution in the eighties, Natural orifice transluminal endoscopic surgery
      (NOTES) must be watched on closely, and will probably have to be taken into
      account in a near future. Minimal invasive procedures in oesophageal cancer
      surgery have proved both efficient and oncologically safe. Implementation of Fast
      track protocols now permits a much faster patient's return to normal daily
      activity. In hepatobiliary and pancreatic surgery, multidisciplinary efforts have
      been done to better select patients, widen the indications and increase
      efficiency.

PMID- 18335891
TI  - [Secret defences].

PMID- 18335890
TI  - [What's new in ENT for the practionner in 2007?].
AB  - Importance of biofims, detected on adenoids. Incidence of post-tonsillectomy
      hemorage increased in summer and winter, interst of a systematic hearing
      screening in newborns, proven interst of nasal irrigation in cases of rhino
      sinusitis, correlation between obesity and nasal obstruction, interst of nasal
      evaluation in cases of Wegener, importance of reffe-red otalgia with normal
      eardrum as an indicator for ENT tumors, observation of neurinomas inpatients over
      65 years, higher and earlier recurrence of T3T4 tumors, while T1T2 tumors of the
      upper aerodigestive tract reccur mostly in the 4th year. Therapeutic impact of
      18FDG-PET/CT in the management of iodine-negative recurrence of differentiated
      thyroid carcinoma, interest of parotid gland biopsy in the diagnosis of patients
      with primary Sjogren's syndrome.

PMID- 18335892
TI  - [Sad dilemmas in contemporary knowledge].

PMID- 18335893
TI  - [Should one hunt down the irrelevance of birth?].

PMID- 18335894
TI  - [France as called on by soap and handkerchiefs].

PMID- 18335895
TI  - [France is lacking in discussion].

PMID- 18335896
TI  - Critical time for critical care.

PMID- 18335897
TI  - Now and then: human ventilators, mechanical students and the birth of paediatric
      intensive care.

PMID- 18335898
TI  - Medically stable children in PICU: better at home.
AB  - A number of medically stable children and young people with complex care needs,
      and in particular those requiring long-term ventilation, are spending
      inappropriately long periods of time in acute hospital settings waiting for
      discharge packages to be formulated. Apart from the impact this has on
      availability of inpatient beds for other children, specifically intensive care
      beds, the hospital environment can be detrimental to the well being of the
      child/young person and family. Discharging these children home requires complex
      multi-agency care packages to be established, with a high degree of co-ordinated
      multi-agency working, planning and commissioning that must be continued in the
      long term. UK governments need to set realistic standards for timely discharge of
      children with complex care needs once they are deemed medically fit. To achieve
      these standards there needs to be additional investment in community children's
      nursing and transitional care units, improved data collection and a UK-wide
      framework for commissioning of services for children and families with complex
      care needs.

PMID- 18335899
TI  - Weaning from sedation: don't ignore the score.
AB  - The use of sedation and analgesia in critically ill children is necessary for
      clinical management but can result in undesirable side effects such as physical
      dependence, tolerance and withdrawal symptoms. Weaning from sedation aims to
      prevent such unpleasant effects. Regular scoring of signs and symptoms of
      withdrawal is an essential part of the weaning regime, allowing the clinician to
      assess whether reduced doses are causing withdrawal symptoms. However, there are
      wide variations in whether and how scoring systems are used. This variation may
      be the result of high workload, other external pressures, traditional ways of
      working or other factors. Strategies such as an easily accessible scoring flow
      chart, a poster display, improved staff induction or other measures could help to
      improve safety and quality in sedation management.

PMID- 18335900
TI  - Baby on the move: issues in neonatal transport.
AB  - The 2003 review of UK neonatal services led to wide-ranging changes including the
      centralisation of intensive care into level 3 units, the geographical
      organisation of neonatal care into 'networks', and the setting up of dedicated
      network transport teams. Despite these changes, neonatal transport continues to
      be problematic. Approaches to neonatal transportation are not yet standardised
      and this presents logistical problems for staff. Risks need to be considered and
      managed effectively to ensure safety for all involved. Although algorithms are in
      use for general stabilisation of the neonates, more guidance is required for
      effective stabilisation and management of infants with complex/surgical
      conditions. Staff involved in transport need to understand how neonatal
      physiology may be altered during transportation. They should also consider the
      legal implications of neonatal transport which are likely to remain unclear until
      the law is challenged in some way.

PMID- 18335901
TI  - Reflections on student nurse placements in the PICU.
AB  - Student placements in the paediatric intensive care unit (PICU) have a number of
      benefits including the recruitment of staff to this specialty, students' learning
      of important observational skills and reenforcing the knowledge and skills of
      existing staff. However, the combination of critically ill children and large
      amounts of complex equipment can be daunting for the student nurse commencing a
      clinical placement in PICU. Careful induction, ongoing mentoring and
      opportunities to explore issues help to overcome students' fears of being unable
      to cope, and support the application of theory to practice in this challenging
      environment.

PMID- 18335902
TI  - Vital signs.

PMID- 18335903
TI  - Advanced nursing practice in paediatric critical care.
AB  - Following the successful implementation of High Dependency Care: a model for
      development at King's College hospital in 2005, the authors wished to consider
      the addition of a fourth tier to the model. A review of the clinical environment
      was undertaken and it was suggested that the introduction of an advanced nurse
      practitioner could contribute to the education and continuation of the outreach
      service detailed in the model, as well as to the improvement of critical care
      services and career development opportunities for nurses within the unit. A
      survey was undertaken to identify the views of medical and nursing staff about
      essential roles and responsibilities of advanced nurse practitioners in this
      area. This would then direct the development of a teaching and competency
      programme that could promote advanced practice in the critical care environment.
      There was no consensus on the tasks advanced nurse practitioners can undertake,
      the appropriate mentors in the clinical environment, the level of education they
      must achieve, nor the time in which this should be completed. There was confusion
      about the qualifications required for advanced nursing practice, mentorship and
      training. However, there was support for this role and respondents confirmed the
      view that advanced nursing practiced would be beneficial in patient care
      delivery.

PMID- 18335904
TI  - Accounting for care: Healthcare Resource Groups for paediatric critical care.
AB  - Healthcare Resource Groups are a way of grouping patients in relation to the
      amount of healthcare resources they consume. They are the basis for
      implementation of Payment by Results by the Department of Health in England. An
      expert working group was set up to define a dataset for paediatric critical care
      that would in turn support the derivation of Healthcare Resource Groups. Three
      relevant classification systems were identified and tested with data from ten
      PICUs, including data about diagnoses, number of organ systems supported,
      interventions and nursing activity. Each PICU provided detailed costing for the
      financial year 2005/2006. Eighty-three per cent of PICU costs were found to be
      related to staff costs, with the largest cost being nursing costs. The Nursing
      Activity Score system was found to be a poor predictor of staff resource use, as
      was the adult HRG model based on the number of organ systems supported. It was
      decided to develop the HRGs based on a 'levels of care' approach; 32 data items
      were defined to support HRG allocation. From October 2007, data have been
      collected daily to identify the HRGs for each PICU patient and are being used by
      the Department of Health to estimate reference costs for PICU services. The data
      can also be used to support improved audit of PICU activity nationally as well as
      comparison of workload across different units and modelling of staff requirements
      within a unit.

PMID- 18335905
TI  - The theory-practice gap: ECMO research example.
AB  - AIM: The time taken for research findings to enter clinical practice can be very
      lengthy. A contributing factor is the time lag between the research literature
      identifying the issue, and medical and nursing texts discussing it. The example
      of ECMO (Extracorporeal Membrane Oxygenation) is used to examine this issue,
      specifically the extent to which relevant nursing journals and textbooks discuss
      the effects of ECMO on medication. METHOD: A systematic review of papers
      identifying the problem (pharmacokinetics in ECMO patients) and the dissemination
      of this to clinicians was undertaken. Publications used by those exploring the
      problem were most likely to be found in Medline, and those disseminating to
      nurses in CINAHL. Textbooks on neonatal nursing and paediatric intensive care
      with sections on ECMO were also explored. RESULTS: There are several studies that
      show drug delivery is altered in patients receiving ECMO, dating back to 1989.
      Only three papers likely to be accessed by clinicians were found to address the
      effect of ECMO on drug delivery. Two of the textbooks addressed these issues but
      it took eight years from the issue being first raised to any medical or nursing
      text discussing it. CONCLUSION: Nurses will most likely not be aware of the
      latest research in their area if they rely on textbooks. Advanced education that
      gives critical appraisal and literature-searching skills, such as found in
      master's courses, should help the clinical nurse employ evidence based practice.

PMID- 18335906
TI  - Pi and sigma-phenylethynyl radicals and their isomers o-, m-, and p
      ethynylphenyl: structures, energetics, and electron affinities.
AB  - Molecular structures, energetics, vibrational frequencies, and electron
      affinities are predicted for the phenylethynyl radical and its isomers. Electron
      affinities are computed using density functional theory, -namely, the BHLYP,
      BLYP, B3LYP, BP86, BPW91, and B3PW91 functionals-, employing the double-zeta plus
      polarization DZP++ basis set; this level of theory is known to perform well for
      the computation of electron affinities. Furthermore, ab initio computations
      employing perturbation theory, coupled cluster with single and double excitations
      [CCSD], and the inclusion of perturbative triples [CCSD(T)] are performed to
      determine the relative energies of the isomers. These higher level computations
      are performed with the correlation consistent family of basis sets cc-pVXZ (X =
      D, T, Q, 5). Three electronic states are probed for the phenylethynyl radical. In
      C2v symmetry, the out-of-plane (2B1) radical is predicted to lie about 10
      kcal/mol below the in-plane (2B2) radical by DFT methods, which becomes 9.4
      kcal/mol with the consideration of the CCSD(T) method. The energy difference
      between the lowest pi and sigma electronic states of the phenylethynyl radical is
      also about 10 kcal/mol according to DFT; however, CCSD(T) with the cc-pVQZ basis
      set shows this energy separation to be just 1.8 kcal/mol. The theoretical
      electron affinities of the phenylethynyl radical are predicted to be 3.00 eV
      (B3LYP/DZP++) and 3.03 eV (CCSD(T)/DZP++//MP2/DZP++). The adiabatic electron
      affinities (EAad) of the three isomers of phenylethynyl, that is, the ortho-,
      meta-, and para-ethynylphenyl, are predicted to be 1.45, 1.40, and 1.43 eV,
      respectively. Hence, the phenylethynyl radical binds an electron far more
      effectively than the three other radicals studied. Thermochemical predictions,
      such as the bond dissociation energies of the aromatic and ethynyl C-H bonds and
      the proton affinities of the phenylethynyl and ethynylphenyl anions, are also
      reported.

PMID- 18335907
TI  - Correlation of transverse and rotational diffusion coefficient: a probe of
      chemical composition in hydrocarbon oils.
AB  - Measurements of relaxation time and diffusion coefficient by nuclear magnetic
      resonance are well-established techniques to study molecular motions in fluids.
      Diffusion measurements sense the translational diffusion coefficients of the
      molecules, whereas relaxation times measured at low magnetic fields probe
      predominantly the rotational diffusion of the molecules. Many complex fluids are
      composed of a mixture of molecules with a wide distribution of sizes and chemical
      properties. This results in correspondingly wide distributions of measured
      diffusion coefficients and relaxation times. To first order, these distributions
      are determined by the distribution of molecular sizes. Here we show that
      additional information can be obtained on the chemical composition by measuring
      two-dimensional diffusion-relaxation distribution functions, a quantity that
      depends also on the shape and chemical interactions of molecules. We illustrate
      this with experimental results of diffusion-relaxation distribution functions on
      a series of hydrocarbon mixtures. For oils without significant amounts of
      asphaltenes, the diffusion-relaxation distribution functions follow a power-law
      behavior with an exponent that depends on the relative abundance of saturates and
      aromatics. Oils with asphaltene deviate from this trend, as asphaltene molecules
      act as relaxation contrast agent for other molecules without affecting their
      diffusion coefficient significantly. In waxy oils below the wax appearance
      temperature a gel forms. This is reflected in the measured diffusion-relaxation
      distribution functions, where the restrictions due to the gel network reduce the
      diffusion coefficients without affecting the relaxation rates significantly.

PMID- 18335908
TI  - Metastability of MCM-41 and Al-MCM-41.
AB  - The apparent stability of MCM-41 and Al-MCM-41 in water was appraised in a series
      of solubility experiments. MCM-41 is a siliceous, mesoporous material of
      hexagonal symmetry and exceptionally high surface area first synthesized in 1992.
      The dissolution experiments were carried out at several solid/water ratios:
      1/200, 1/100, and 1/75. Results indicated that MCM-41 and Al-MCM-41 are more
      soluble than amorphous silica at ambient temperatures. Using standard
      thermodynamic data, a minimum Gibbs free energy of formation of -847.9 kJ/mol for
      MCM-41 was calculated compared to -848.85 kJ/mol for amorphous silica and -856.3
      kJ/mol for quartz. X-ray diffraction (XRD) analyses of recovered solids indicated
      a progressive loss of crystallinity in MCM-41 and Al-MCM-41 over the 79 day
      dissolution experiment. BET nitrogen surface area analyses of recovered solids
      revealed no appreciable change in the surface area of either material after 79
      days of reaction in water. Field emission scanning electron microscope (SEM)
      images taken of the 79 day MCM-41 sample showed some degradation of the initial
      structure-fine, worm-like particles.

PMID- 18335909
TI  - Theoretical study of hydrogen abstraction and sulfur insertion in the reaction
      H2S + S.
AB  - The reaction of H2S + S has been characterized at the multireference
      configuration interaction level with the geometries optimized using the aug-cc
      pVTZ basis set and the single-point energy calculated using the aug-cc-pV(Q+d)Z
      basis set. As in the analogous reaction of H2 + S, the presence of an intersystem
      crossing enables products (SH + SH) to be formed on the singlet surface through S
      insertion, which bypasses the triplet barrier (19.1 kJ mol-1 relative to SH + SH)
      of the H abstraction route. This provides theoretical evidence for SH + SH
      formation without barrier beyond endothermicity at sufficiently low temperatures.
      The H abstraction route, however, is expected to be competitive at higher
      temperatures due to a much higher Arrhenius pre-exponential factor (6.9 x 10(14)
      cm3 mol-1 s-1 derived from TST calculation) than that of S insertion channel (3.7
      x 10(13) cm3 mol-1 s-1, derived by a least-squares fit to the measurements). With
      a slightly higher transition-state barrier than that of the H abstraction
      channel, the production of S2 + H2 is less favored due to proceeding via
      intersystem crossing and insertion. While the formation of HSS + H is
      energetically unfavorable relative to SH + SH, recombination channels producing
      H2SS or the more stable HSSH are expected to occur under collisional
      stabilization conditions at high pressures.

PMID- 18335910
TI  - Radiation-induced decomposition of PETN and TATB under extreme conditions.
AB  - We conducted a series of experiments investigating decomposition of secondary
      explosives PETN and TATB at varying static pressures and temperatures using
      synchrotron radiation. As seen in our earlier work, the decomposition rate of
      TATB at ambient temperature slows systematically with increasing pressure up to
      at least 26 GPa but varies little with pressure in PETN at ambient temperature up
      to 15.7 GPa, yielding important information pertaining to the activation complex
      volume in both cases. We also investigated the radiation-induced decomposition
      rate as a function of temperature at ambient pressure and 26 GPa for TATB up to
      403 K, observing that the decomposition rate increases with increasing
      temperature as expected. The activation energy for the TATB reaction at ambient
      temperature was experimentally determined to be 16 +/- 3 kJ/mol.

PMID- 18335911
TI  - Photoinduced energy and electron-transfer processes in porphyrin-perylene
      bisimide symmetric triads.
AB  - The photophysics of two symmetric triads, (ZnP)2PBI and (H2P)2PBI, made of two
      zinc or free-base porphyrins covalently attached to a central perylene bisimide
      unit has been investigated in dichloromethane and in toluene. The solvent has
      been shown to affect not only quantitatively but also qualitatively the
      photophysical behavior. A variety of intercomponent processes (singlet energy
      transfer, triplet energy transfer, photoinduced charge separation, and
      recombination) have been time-resolved using a combination of emission
      spectroscopy and femtosecond and nanosecond time-resolved absorption techniques
      yielding a very detailed picture of the photophysics of these systems. The
      singlet excited state of the lowest energy chromophore (perylene bisimide in the
      case of (ZnP)2PBI, porphyrin in the case of (H2P)2PBI) is always quantitatively
      populated, besides by direct light absorption, by ultrafast singlet energy
      transfer (few picosecond time constant) from the higher energy chromophore. In
      dichloromethane, the lowest excited singlet state is efficiently quenched by
      electron transfer leading to a charge-separated state where the porphyrin is
      oxidized and the perylene bisimide is reduced. The systems then go back to the
      ground state by charge recombination. The four charge separation and
      recombination processes observed for (ZnP)2PBI and (H2P)2PBI in dichloromethane
      take place in the sub-nanosecond time scale. They obey standard free-energy
      correlations with charge separation lying in the normal regime and charge
      recombination in the Marcus inverted region. In less polar solvents, such as
      toluene, the energy of the charge-separated states is substantially lifted
      leading to sharp changes in photophysical mechanism. With (ZnP)2PBI, the electron
      transfer quenching is still fast, but charge recombination takes place now in the
      nanosecond time scale and to triplet state products rather than to the ground
      state. Triplet-triplet energy transfer from the porphyrin to the perylene
      bisimide is also involved in the subsequent deactivation of the triplet manifold
      to the ground state. With (H2P)2PBI, on the other hand, the driving force for
      charge separation is too small for electron-transfer quenching, and the
      deactivation of the porphyrin excited singlet takes place via intersystem
      crossing to the triplet followed by triplet energy transfer to the perylene
      bisimide and final decay to the ground state.

PMID- 18335912
TI  - Theoretical comparison of ketene dimerization in the gas and liquid phase.
AB  - We present the first theoretical comparison between ketene dimerization in gas
      phase and ketene dimerization in solution. Density functional theory (DFT)
      calculations on the ketene dimerization were carried out considering the
      following product dimers: diketene (d-I), 1,3-cyclobutanedione (d-II), 2,4
      dimethylene-1,3-dioxetane (d-III), and 2-methyleneoxetan-3-one (d-IV). All
      structures were optimized at the PW86x+PBEc/DZP level of theory. Based on these
      geometries, a total of 58 meta and hybrid functionals were used to evaluate the
      heat of dimerization. The MPW1K functional was found to fit the experimental data
      best and subsequently used in the final analyses for all energy calculations. It
      was found on both kinetic and thermodynamic grounds that only d-I and d-II are
      formed during ketene dimerization in gas phase and solution. In gas phase, d-I is
      favored over d-II by 2 kcal/mol. However, the dimerization barrier for d-I is 1
      kcal/mol higher than for d-II. Solvation makes dimerization more favorable. On
      the enthalpic surface this is due to a favorable interaction between the dimer
      dipole moment and solvent molecules. The dimer is stabilized further on the Gibbs
      energy surface by an increase of the dimerization entropy in solution compared to
      gas phase. The species d-I remains the most stable dimer in solution by 1
      kcal/mol. Kinetically, the dimerization barriers for the relevant species d-I and
      d-II are cut in half by solvation, due to both favorable dimer-dipole/solvent
      interactions (DeltaH++, DeltaG++) and an increase in the activation entropies
      (DeltaS++). While the dimerization barrier for d-II is lowest for the gas phase
      and toluene, the barrier for d-I formation becomes lowest for the more polar
      solvent acetone by 1 kcal/mol as d-I dimerization has the most polar transition
      state.

PMID- 18335913
TI  - Gas production in the radiolysis of poly(vinyl chloride).
AB  - The yields of H2 and Cl- were determined in the radiolysis of deaerated, aerated,
      and water mixtures of poly(vinyl chloride) (PVC) powders with gamma-rays and 5
      MeV He ions. H2 yields with gamma-rays are low at about 0.25 molecule/100 eV and
      they double with He ion radiolysis indicating a second order formation process.
      The production of H2 in the gamma-radiolysis of water-PVC mixtures is much
      greater than expected from the weight fraction of the components and is due to
      acidification of the aqueous phase by the evolution of HCl from the polymer. Cl-
      yields in the gamma-radiolysis of PVC with number average weights of 22,000,
      47,000, and 99,000 Daltons are 19.6, 33.8, and 32.5 atoms/100 eV. Cl-
      continuously evolves from the polymer for days following radiolysis. The
      extremely large yields suggest that a chain process involving radicals stabilized
      on the polymeric chain are responsible. Reflectance UV/vis and infrared
      spectroscopy show subtle changes in the PVC with radiolysis while UV/vis
      absorption spectra clearly indicate the formation of polyenes with 1 to 11 units.
      Cl- formation is probably initiated by Cl radical production followed by an
      electron rearrangement mechanism along the PVC chain to produce more Cl- and
      polyenes.

PMID- 18335914
TI  - Ionization of imidazole in the gas phase, microhydrated environments, and in
      aqueous solution.
AB  - Hydration of neutral and cationic imidazole is studied by means of ab initio and
      molecular dynamics calculations, and by photoelectron spectroscopy of the neutral
      species in a liquid microjet. The calculations show the importance of long range
      solvent polarization and of the difference between the structure of water
      molecules in the first shell around the neutral vs cationic species for
      determining vertical and adiabatic ionization potentials. The vertical ionization
      potential of neutral imidazole of 8.06 eV calculated using a nonequilibrium
      polarizable continuum model agrees well with the value of 8.26 eV obtained
      experimentally for an aqueous solution at pH 10.6.

PMID- 18335915
TI  - On the uptake of ammonia by the water/vapor interface.
AB  - The passage of a single ammonia molecule from an infinitely dilute gas through
      the water/vapor interface is studied by constrained molecular dynamics
      simulations. The free energy of the system as a function of the distance between
      the ammonia and the interface has a minimum in the interfacial region. It is
      found that the preference of the ammonia for the interface is mainly due the
      disruption of the solvent structure caused by the ammonia in the bulk region,
      which results in an increase of the solvent internal energy.

PMID- 18335916
TI  - CO activation on the late lanthanide dimers: matrix infrared spectra of the
      Ln2[eta2(mu2-C, O)]x (Ln = Tb, Dy, Ho, Er, Lu; x = 1, 2) molecules.
AB  - Reactions of laser-ablated late lanthanide atoms (Tb, Dy, Ho, Er, Tm, Yb, and Lu)
      with dilute carbon monoxide molecules in solid argon have been investigated using
      matrix-isolation infrared spectroscopy. The Ln2[eta2(mu2-C, O)]x (Ln = Tb, Dy,
      Ho, Er, Lu; x = 1, 2) molecules are observed upon sample annealing, whereas no
      product is observed for Tm and Yb. The C-O stretching frequencies in these
      dilanthanide carbonyls range from 1100 to 1300 cm-1, far below the value of free
      CO in the gas phase (2143.5 cm-1), implying that the C-O bonds are highly
      activated. Density functional theory calculations have been performed on these
      products. These Ln2[eta2(mu2-C, O)]x molecules are predicted to have planar
      structures, which carry asymmetrically bridging CO moieties that are tilted to
      the side.

PMID- 18335917
TI  - Aggregate properties of sodium deoxycholate and dimyristoylphosphatidylcholine
      mixed micelles.
AB  - Mixed micelles of the phospholipid dimyristoylphosphatidylcholine (DMPC) and bile
      salts of sodium deoxycholate (NaDC) were investigated by a combination of
      techniques, including time-resolved fluorescence quenching (TRFQ), electron spin
      resonance (ESR), viscometry, pulsed-gradient spin-echo NMR (PGSE-NMR), and
      surface tensiometry. Aggregation numbers, and bimolecular collision rate
      constants of guest molecules confined in the micelles (by TRFQ), interfacial
      hydration index and microviscosity, (by ESR), axial ratio (from solution
      viscosity), micelle self-diffusion coefficient (by PGSE-NMR), and the critical
      micelle concentrations (from surface tension) were determined for various molar
      compositions defined by the ratio R identical with [NaDC]/[DMPC] and
      concentrations ([NaDC]+[DMPC]). The data interpretation showed the micelles to be
      polydisperse rods. Aggregate properties depend on the ratio, R and reveal
      behavior unlike that in micelles of surfactants with aliphatic nonpolar chains.
      With increase in concentration from [NaDC] = 0.010 M to [NaDC] = 0.200 M, the
      hydration index and the aggregation number exhibit non-monotonic variations.
      Formulation of a polar shell model for cylindrical micelles yielded a set of
      nonlinear equations for the structural features of the micelle. The solutions
      give the microstructural description of the mixed micelle that includes the
      length, diameter, number of water molecules in the hydration shell, and the
      monomer organization in the micelle.

PMID- 18335918
TI  - Molecular and morphological characterization of bis benzimidazo perylene films
      and surface-enhanced phenomena.
AB  - Thin solid films of bis benzimidazo perylene (AzoPTCD) were fabricated using
      physical vapor deposition (PVD) technique. Thermal stability and integrity of the
      AzoPTCD PVD films during the fabrication ( approximately 400 degrees C at 10(-6)
      Torr) were monitored by Raman scattering. Complementary thermogravimetric results
      showed that thermal degradation of AzoPTCD occurs at 675 degrees C. The growth of
      the PVD films was established through UV-vis absorption spectroscopy, and the
      surface morphology was surveyed by atomic force microscopy (AFM) as a function of
      the mass thickness. The AzoPTCD molecular organization in these PVD films was
      determined using the selection rules of infrared absorption spectroscopy
      (transmission and reflection-absorption modes). Despite the molecular packing, X
      ray diffraction revealed that the PVD films are amorphous. Theoretical
      calculations (density functional theory, B3LYP) were used to assign the
      vibrational modes in the infrared and Raman spectra. Metallic nanostructures,
      able to sustain localized surface plasmons (LSP) were used to achieve surface
      enhanced resonance Raman scattering (SERRS) and surface-enhanced fluorescence
      (SEF).

PMID- 18335919
TI  - Characterization of EVA/clay nanocomposite membranes and its pervaporation
      performance.
AB  - Pervaporation separation of chlorinated hydrocarbon/acetone mixtures has been
      investigated using nanoclay modified poly(ethylene-co-vinyl acetate) films. The
      results have been compared with the unfilled poly(ethylene-co-vinyl acetate)
      films. The nanoclay modified membranes were characterized by X-ray diffraction
      technique. The dispersion of layered silicates in the polymer matrix was analyzed
      using transmission electron microscopy. The nanoclay showed excellent dispersion
      in the polymer matrix. The effect of free volume on the pervaporation performance
      was investigated by positron annihilation lifetime spectroscopy. Poly(ethylene-co
      vinyl acetate) nanocomposite membrane showed high selectivity because of the
      plateletlike morphology and high aspect ratio of layered silicates. The nano clay
      content and the swelling effects on pervaporation performance of nano composite
      membranes have been investigated in detail.

PMID- 18335920
TI  - An aggregation-volume-bias Monte Carlo investigation on the condensation of a
      Lennard-Jones vapor below the triple point and crystal nucleation in cluster
      systems: an in-depth evaluation of the classical nucleation theory.
AB  - The aggregation-volume-bias Monte Carlo based simulation technique, which has led
      to our recent success in vapor-liquid nucleation research, was extended to the
      study of crystal nucleation processes. In contrast to conventional bulk-phase
      techniques, this method deals with crystal nucleation events in cluster systems.
      This approach was applied to the crystal nucleation of Lennard-Jonesium under a
      wide range of undercooling conditions from 35% to 13% below the triple point. It
      was found that crystal nucleation in these model clusters proceeds initially via
      a vapor-liquid like aggregation followed by the formation of crystals inside the
      aggregates. The separation of these two stages of nucleation is distinct except
      at deeper undercooling conditions where the crystal nucleation barrier was found
      to diminish. The simulation results obtained for these two nucleation steps are
      separately compared to the classical nucleation theory (CNT). For the vapor
      liquid nucleation step, the CNT was shown to provide a reasonable description of
      the critical cluster size but overestimate the barrier heights, consistent with
      previous simulation studies. On the contrary, for the crystal nucleation step,
      nearly perfect agreement with the barrier heights was found between the
      simulations and the CNT. For the critical cluster size, the comparison is more
      difficult as the simulation data were found to be sensitive to the definition of
      the solid cluster, but a stringent criterion and lower undercooling conditions
      generally lead to results closer with the CNT. Additional simulations at
      undercooling conditions of 40% or above indicate a nearly barrierless transition
      from the liquid to crystalline-like structure for sufficiently large clusters,
      which leads to further departure of the barrier height predicted by the CNT from
      the simulation data for the aggregation step. This is consistent with the latest
      experimental results on argon that show an unusually large underestimation of the
      nucleation rate by the CNT toward deep undercooling conditions.

PMID- 18335921
TI  - Largely improved tensile properties of chitosan film via unique synergistic
      reinforcing effect of carbon nanotube and clay.
AB  - In this work, a great synergistic effect of 2D clay platelets and 1D carbon
      nanotubes (CNTs) on reinforcing chitosan matrix has been observed for the first
      time. With incorporation of 3 wt % clay and 0.4 wt % CNTs, the tensile strength
      and Young's modulus of the nanocomposites are significantly improved by about 171
      and 124%, respectively, compared with neat chitosan. This could be understood as
      due to the formation of much jammed fillers network with 1D CNTs and 2D clay
      platelets combined together, as indicated by rheological measurement. Our work
      demonstrates a good example for the preparation of high performance polymer
      nanocomposites by using nanofillers of different dimension together.

PMID- 18335922
TI  - Structures and energetics of base flipping of the thymine dimer depend on DNA
      sequence.
AB  - The cis,syn-cyclobutane pyrimidine dimer (CPD) is a photoinduced DNA lesion
      leading to a significant distortion of the DNA structure. Its repair by DNA
      photolyase requires a flip of the damaged base into an extrahelical position.
      This base flip is expected to be sequence-dependent, but the structures and
      energetics as a function of the bases 3' and 5' to the CPD lesion are unknown.
      Eight-nanosecond MD simulations of four different hexadecamer duplexes with the
      CPD were performed for the flipped-in and flipped-out structures. Analysis of
      these results indicates clear sequence-dependent differences. Significant
      disruptions of the base pairs to the 3' side of the CPD are observed for the
      flipped-out structures with adjacent A-T pairs, whereas those with G-C pairs
      adjacent show no such distortions. The conformational spaces occupied by these
      two duplexes are significantly different. The structural differences correlate
      well with the free energy differences for base flipping calculated using the
      previously established 2D potential of mean force (PMF) method. The energy
      differences for base flipping in duplexes containing A, T, G, and C pairs
      adjacent to the CPD were found to be 6.25-6.5, 5.25-5.5, 7.25-7.5, and 6.5-6.75
      kcal/mol, respectively. These energy differences of up to 2 kcal/mol should be
      large enough to be detected experimentally using sensitive probes.

PMID- 18335923
TI  - Effect of dual fullerenes on lifetimes of charge-separated States of
      subphthalocyanine-triphenylamine-fullerene molecular systems.
AB  - Photoinduced intramolecular electron-transfer events of the newly synthesized
      subphthalocyanine-triphenylamine-fullerene triad (SubPc-TPA-C60) and
      subphthalocyanine-triphenylamine-bisfullerene tetrad (SubPc-TPA-(C(60))(2)) were
      studied. The geometric and electronic structures of the triad were probed by ab
      initio B3LYP/3-21G method, which predicts SubPc-TPA(*+)-C(60)(*-) as a stable
      charge-separated state. The photoinduced events via the excited singlet state of
      SubPc were monitored by time-resolved emission measurements as well as transient
      absorption techniques. Efficient charge-separations via the excited states of
      SubPc were observed with the rates of approximately 10(10) s(-)1. Compared with
      the SubPc-TPA dyad, a long-lived charge-separated state was observed for the
      SubPc-TPA-C(60) triad with the lifetime of the radical ion pairs (tau(RIP)) of
      670 ns in benzonitrile. Interestingly, further charge stabilization was achieved
      in the charge-separated state of SubPc-TPA-(C(60))(2), in which the tau(RIP) was
      found to be 1050 ns in benzonitrile.

PMID- 18335924
TI  - Enhancement of reaction specificity at interfaces.
AB  - A realistic picture of a cell is that of a highly viscous, condensed gel-like
      substance, crowded with macromolecules that are mostly anchored to membranes and
      to intricate networks of cytoskeletal elements. Theoretical and experimental
      approaches to investigating crowding have not considered the role of diffusion
      through a crowded medium in affecting the selectivity and specificity of
      reactions. Such diffusion is especially important when one considers interfaces,
      where at least one reactant must move through the medium and reach the interface.
      Here, we address this issue by directly investigating how diffusion through a gel
      medium affects the competition between a single specific reaction and a large
      number of weak nonspecific interactions, a process that is typical of reactions
      occurring at interfaces. We present an approach for achieving orientation
      controlled interactions based on the configuration-dependent diffusion rate of
      the reacting molecule through a gel medium. The effectiveness of the method is
      demonstrated by the high selectivity obtained both in the adsorption of DNA to a
      surface and in DNA hybridization to preadsorbed single-strand oligomer on a
      surface.

PMID- 18335925
TI  - Polyaniline based nucleic acid sensor.
AB  - Twenty-bases long NH2-modified DNA and PNA probes specific to a pathogen
      (Mycobacterium tuberculosis) were covalently immobilized onto a polyaniline
      (PANI)/Au electrode to detect nucleic acid hybridization with complementary, one
      base mismatch and noncomplementary targets within 30 s using Methylene Blue. The
      PNA-PANI/Au electrode exhibits improved specificity (1000 times) and detection
      limit (0.125 x 10(-18) M) as compared to that of the DNA-PANI/Au electrode (2.5 x
      10(-18) M). These PNA-PANI/Au electrodes can be utilized for detection of
      hybridization with the complementary sequence in 5 min sonicated M. tuberculosis
      genomic DNA within 1 min of hybridization time. These DNA-PANI/Au and PNA-PANI/Au
      electrodes can be used 6-7 and 13-15 times, respectively.

PMID- 18335926
TI  - Chronoamperometry and cyclic voltammetry at conical electrodes, microelectrodes,
      and electrode arrays: theory.
AB  - The finite difference method is used to simulate chronoamperometry, linear sweep
      voltammetry, and cyclic voltammetry at conical electrodes and microelectrodes.
      Techniques for the numerical simulation of these processes at microdiscs are
      adapted and extended to accurately model diffusion to the electroactive cone
      surface. Simulated results are analyzed, and trends are rationalized in terms of
      the cone apex angle, alpha. The diffusion domain approximation is used to extend
      the theory to regular and random arrays of conical electrodes.

PMID- 18335927
TI  - The degree of structural protection at the edge beta-strands determines the
      pathway of amyloid formation in globular proteins.
AB  - The assembly of proteins into highly organized fibrillar aggregates is a key
      process in biology, biotechnology, and human disease. It has been shown that
      proteins retain a small, yet significant propensity to aggregate when they are
      folded into compact globular structures, and this may be physiologically
      relevant, particularly when considering that proteins spend most of their
      lifespan into such compact states. Proteins from the acylphosphatase-like
      structural family have been shown to aggregate via different mechanisms, with
      some members forming native-like aggregates as a first step of their aggregation
      process and others requiring unfolding as a first necessary step. Here we use the
      acylphosphatase from Sulfolobus solfataricus to show that assembly of folded
      protein molecules into native-like aggregates is prevented by single-point
      mutations that introduce structural protections within one of the most flexible
      region of the protein, the peripheral edge beta-strand 4. The resulting mutants
      do not form native-like aggregates, but can still form thioflavin T-binding and
      beta-structured oligomers, albeit more slowly than the wild-type protein. The
      kinetic data show that formation of the latter species proceeds via an
      alternative mechanism that is independent of the transient formation of native
      like aggregates.

PMID- 18335928
TI  - Mechanisms of inter- and intramolecular communication in GPCRs and G proteins.
AB  - This study represents the first attempt to couple, by computational experiments,
      the mechanisms of intramolecular and intermolecular communication concerning a
      guanidine nucleotide exchange factor (GEF), the thromboxane A2 receptor (TXA2R),
      and the cognate G protein (Gq) in its heterotrimeric GDP-bound state. Two-way
      pathways mediate the communication between the receptor-G protein interface and
      both the agonist binding site of the receptor and the nucleotide binding site of
      the G protein. The increase in solvent accessibility in the neighborhoods of the
      highly conserved E/DRY receptor motif, in response to agonist binding, is
      instrumental in favoring the penetration of the C-terminus of Gqalpha in between
      the cytosolic ends of H3, H5, and H6. The arginine of the E/DRY motif is
      predicted to be an important mediator of the intramolecular and intermolecular
      communication involving the TXA2R. The receptor-G protein interface is predicted
      to involve multiple regions from the receptor and the G protein alpha-subunit.
      However, receptor contacts with the C-terminus of the alpha5-helix seem to be the
      major players in the receptor-catalyzed motion of the alpha-helical domain with
      respect to the Ras-like domain and in the formation of a nucleotide exit route in
      between the alphaF-helix and beta6/alpha5 loop of Gqalpha. The inferences from
      this study are of wide interest, as they are expected to apply to the whole
      rhodopsin family, given also the considerable G protein promiscuity.

PMID- 18335929
TI  - Preparation of microscopic and planar oil-water interfaces that are decorated
      with prescribed densities of insoluble amphiphiles.
AB  - Langmuir monolayers (monolayers of insoluble molecules formed at the surface of
      water), and associated Langmuir-Blodgett/Schaefer monolayers prepared by transfer
      of Langmuir films to the surfaces of solids, are widely used in studies aimed at
      understanding the physicochemical properties of biological and synthetic
      molecules at interfaces. In this article, we report a general and facile
      procedure that permits transfer of Langmuir monolayers from the surface of water
      onto microscopic and planar interfaces between oil and aqueous phases. In these
      experiments, a metallic grid supported on a hydrophobic solid is used to form oil
      films with thicknesses of 20 mum and interfacial areas of 280 mum x 280 mum.
      Passage of the supported oil films through a Langmuir monolayer is shown to lead
      to quantitative transfer of insoluble amphiphiles onto the oil-water interfaces.
      The amphiphile-decorated oil-water interfaces hosted within the metallic grids
      (i) are approximately planar, (ii) are sufficiently robust mechanically so as to
      permit further characterization of the interfaces outside of the Langmuir trough,
      (iii) can be prepared with prescribed and well-defined densities of amphiphiles,
      and (iv) require only approximately 200 nL of oil to prepare. The utility of this
      method is illustrated for the case of the liquid crystalline oil 4-pentyl-4'
      cyanobiphenyl (5CB). Transfer of monolayers of either dilauroyl- or
      dipalmitoylphosphatidylcholine (DLPC and DPPC, respectively) to the nematic 5CB
      aqueous interface is demonstrated by epifluorescence imaging of fluorescently
      labeled lipid and polarized light imaging of the orientational order within the
      thin film of nematic 5CB. Interfaces prepared in this manner are used to reveal
      key differences between the density-dependent phase properties of DLPC and DPPC
      monolayers formed at air-water as compared to that of nematic 5CB-aqueous
      interfaces. The methodology described in this article should be broadly useful in
      advancing studies of the interfacial behavior of synthetic and biological
      molecules at liquid-liquid interfaces.

PMID- 18335930
TI  - Conversion of anisotropically phase-segregated Pd/gamma-Fe2O3 nanoparticles into
      exchange-coupled fct-FePd/alpha-Fe nanocomposite magnets.
AB  - Exchange-coupled fct-FePd/alpha-Fe nanocomposite magnets were fabricated by
      converting anisotropically phase-segregated Pd/gamma-Fe2O3 nanoparticles via the
      interfacial atom diffusion. The magnetically hard fct-FePd phases formed by the
      interdiffusion between alpha-Fe and fcc-Pd phases nearly preserve their sizes at
      the nanometer scale because they are surrounded by the alpha-Fe matrix. The VSM
      measurements reveal that the exchange coupling between the soft and hard phases
      has been realized.

PMID- 18335932
TI  - Pressure-induced polymerization of diiodobutadiyne in assembled cocrystals.
AB  - Diiodobutadiyne forms cocrystals with bis(pyridyl)oxalamides in which the diyne
      alignment is near the ideal parameters for topochemical polymerization to the
      ordered conjugated polymer, poly(diiododiacetylene) (PIDA). Nonetheless, previous
      efforts to induce polymerization in these samples via heat or irradiation were
      unsuccessful. We report here the successful ordered polymerization of
      diiodobutadiyne in these cocrystals, by subjecting them to high external pressure
      (0.3-10 GPa). At the lower end of the pressure range, the samples contain
      primarily monomer, as demonstrated by X-ray diffraction studies, but some
      polymerization does occur, leading to a pronounced color change from colorless to
      blue and to the development of intense Raman peaks at 962, 1394, and 2055 cm-1,
      corresponding to the poly(diacetylene). At higher pressures, the samples turn
      black and contain primarily polymer, as determined by solid-state NMR and Raman
      spectroscopy. Both density functional theory calculations (B3LYP/LanL2DZ) and
      comparisons to authentic samples of PIDA have confirmed the data analysis.

PMID- 18335931
TI  - On the nature of antimicrobial activity: a model for protegrin-1 pores.
AB  - We conducted over 150 ns of simulation of a protegrin-1 octamer pore in a lipid
      bilayer composed of palmitoyloleoyl-phosphatidylethanolamine (POPE) and
      palmitoyloleoyl-phosphatidylglycerol (POPG) lipids mimicking the inner membrane
      of a bacterial cell. The simulations improve on a model of a pore proposed from
      recent NMR experiments and provide a coherent understanding of the molecular
      mechanism of antimicrobial activity. Although lipids tilt somewhat toward the
      peptides, the simulated protegrin-1 pore more closely follows the barrel-stave
      model than the toroidal-pore model. The movement of ions is investigated through
      the pore. The pore selectively allows negatively charged chloride ions to pass
      through at an average rate of one ion every two nanoseconds. Only two events are
      observed of sodium ions crossing through the pore. The potential of mean force is
      calculated for the water and both ion types. It is determined that the chloride
      ions move through the pore with ease, similarly to the water molecules with the
      exception of a zone of restricted movement midway through the pore. In bacteria,
      ions moving through the pore will compromise the integrity of the transmembrane
      potential. Without the transmembrane potential as a countermeasure, water will
      readily flow inside the higher osmolality cytoplasm. We determine that the
      diffusivity of water through a single PG-1 pore is sufficient to cause fast cell
      death by osmotic lysis.

PMID- 18335933
TI  - Tandem Rh(i)-catalyzed [(5+2)+1] cycloaddition/aldol reaction for the
      construction of linear triquinane skeleton: total syntheses of (+/-)-hirsutene
      and (+/-)-1-desoxyhypnophilin.
AB  - A tandem reaction involving a Rh(I)-catalyzed two-component [(5+2)+1]
      cycloaddition and an aldol condensation has been developed to construct the
      tricyclo[6.3.0.02,6]undecane skeleton and its heteroatom-imbedded analogues.
      Meanwhile, this method has been successfully applied to natural product synthesis
      for the first time. The present strategy enables a straightforward approach to
      the natural linear triquinane skeleton, as demonstrated by concise and step
      economical syntheses of hirsutene and 1-desoxy-hypnophilin, whereby the linear
      triquinane core is diastereoselectively established in one manipulation with
      correct placement of all stereocenters, including two quarternary centers. This
      first application of the Rh(I)-catalyzed [(5+2)+1] cycloaddition in natural
      product synthesis highlights the efficiency of this methodology for constructing
      complex fused ring systems.

PMID- 18335934
TI  - PASADENA hyperpolarization of succinic acid for MRI and NMR spectroscopy.
AB  - We use the PASADENA (parahydrogen and synthesis allow dramatically enhanced
      nuclear alignment) method to achieve 13C polarization of approximately 20% in
      seconds in 1-13C-succinic-d2 acid. The high-field 13C multiplets are observed as
      a function of pH, and the line broadening of C1 is pronounced in the region of
      the pK values. The 2JCH, 3JCH, and 3JHH couplings needed for spin order transfer
      vary with pH and are best resolved at low pH leading to our use of pH
      approximately 3 for both the molecular addition of parahydrogen to 1-13C-fumaric
      acid-d2 and the subsequent transfer of spin order from the nascent protons to C1
      of the succinic acid product. The methods described here may generalize to
      hyperpolarization of other carboxylic acids. The C1 spin-lattice relaxation time
      at neutral pH and 4.7 T is measured as 27 s in H2O and 56 s in D2O. Together with
      known rates of succinate uptake in kidneys, this allows an estimate of the
      prospects for the molecular spectroscopy of metabolism.

PMID- 18335935
TI  - Near-infrared light activated release of nitric oxide from designed photoactive
      manganese nitrosyls: strategy, design, and potential as NO donors.
AB  - Two new manganese complexes derived from the pentadentate ligand N,N-bis(2
      pyridylmethyl)amine-N-ethyl-2-quinoline-2-carboxamide, PaPy2QH, where H is
      dissociable proton), namely, [Mn(PaPy2Q)(NO)]ClO4 (2) and [Mn(PaPy2Q)(OH)]ClO4
      (3), have been synthesized and structurally characterized. The Mn(III) complex
      [Mn(PaPy2Q)(OH)]ClO4 (3), though insensitive to dioxygen, reacts with nitric
      oxide (NO) to afford the nitrosyl complex [Mn(PaPy2Q)(NO)]ClO4 (2) via reductive
      nitrosylation. This diamagnetic {Mn-NO}6 nitrosyl exhibits nuNO at 1725 cm-1 and
      is highly soluble in water, with lambdamax at 500 and 670 nm. Exposure of
      solutions of 2 to near-infrared (NIR) light (810 nm, 4 mW) results in bleaching
      of the maroon solution and detection of free NO by an NO-sensitive electrode. The
      quantum yield of 2 (Phi = 0.694 +/- 0.010, lambdairr = 550 nm, H2O) is much
      enhanced over the first generation {Mn-NO}6 nitrosyl derived from analogous
      polypyridine ligand, namely, [Mn(PaPy3)(NO)]ClO4 (1, Phi = 0.385 +/- 0.010,
      lambdairr = 550 nm, H2O), reported by this group in a previous account. Although
      quite active in the visible range (500-600 nm), 1 exhibits very little
      photoactivity under NIR light. Both 1 and 2 have been incorporated into sol-gel
      (SG) matrices to obtain nitrosyl-polymer composites 1.SG and 2.SG. The NO
      donating capacities of the polyurethane-coated hybrid materials 1.HM and 2.HM
      have been determined. 2.HM has been used to transfer NO to reduced myoglobin with
      780 nm light. The various strategies for synthesizing photosensitive metal
      nitrosyls have been discussed to establish the merits of the present approach.
      The results of the present study confirm that proper ligand design is a very
      effective way to isolate photoactive manganese nitrosyls that could be used to
      deliver NO to biological targets under the control of NIR light.

PMID- 18335936
TI  - De novo design of strand-swapped beta-hairpin hydrogels.
AB  - De novo designed peptides, capable of undergoing a thermally triggered beta
      strand-swapped self-assembly event leading to hydrogel formation were prepared.
      Strand-swapping peptide 1 (SSP1) incorporates an exchangeable beta-strand domain
      composed of eight residues appended to a nonexchangeable beta-hairpin domain. CD
      shows that, at pH 9 and temperatures less than 35 degrees C, this peptide adopts
      a random coil conformation, rendering it soluble in aqueous solution. On heating
      to 37 degrees C or greater, SSP1 adopts a beta-hairpin that displays an
      exchangeable beta-strand region. The exchangeable strand domain participates in
      swapping with the exchangeable domain of another peptide, affording a strand
      swapped dimer. These dimers further assemble into fibrils that define the
      hydrogel. A second peptide (SSP2) containing an exchangeable strand composed of
      only four residues was also studied. Microscopy and scattering data show that the
      length of the exchangeable domain directly influences the fibril nanostructure
      and can be used as a design element to construct either twisted (SSP1) or
      nontwisted (SSP2) fibril morphologies. CD, FTIR, and WAXS confirm that both
      peptides adopt beta-sheet secondary structure when assembled into fibrils. Fibril
      dimensions, as measured by TEM, AFM, and SANS indicate a fibril diameter of 6.4
      nm, a height of 6.0 nm, and a pitch of 50.4 nm for the twisted SSP1 fibrils. The
      nontwisted SSP2 fibrils are 6.2 nm in diameter and 2.5 nm in height. Oscillatory
      rheology, used to measure bulk hydrogel rigidity, showed that the gel composed of
      the nontwisted fibrils is more mechanically rigid (517 Pa at 6 rad/s) than the
      gel composed of twisted fibrils (367 Pa at 6 rad/s). This work demonstrates that
      beta-strand-swapping can be used to fabricate biomaterials with tunable fibril
      nanostructure and bulk hydrogel rheological properties.

PMID- 18335937
TI  - Unusually weak metal-hydrogen bonds in HV(CO)4(P-P) and their effectiveness as
      H(*) donors.
AB  - The V-H bonds in HV(CO)4(P-P) are unusually weak (55 to 58 kcal/mol). They
      transfer H* to styrene more rapidly than CpCr(CO)3H does and are effective
      stoichiometric reagents for the cyclization of appropriate 1,6-dienes.

PMID- 18335938
TI  - Attaining control by design over the hydrolytic stability of Fe-TAML oxidation
      catalysts.
AB  - The iron(III) complexes of tetra amidato macrocyclic ligands (TAMLs) ([Fe{1-X1-2
      X2C6H2-4,5-(NCOCMe2NCO)2CR2}(OH2)]- , 1: X1 = X2 = H, R2 = Me2 (a), R2 = (CH2)2
      (b); X1 = X2 = Cl, R2 = F2 (c), etc.), which the proton is known to demetalate at
      pH < 3, are also subject to catalyzed demetalation by Bronsted acid buffer
      components at pH 4-9 such as H2PO4-, HSO3-, and CH3CO2H, HO2CCH2CO2-. Buffers
      based on pyridine (py) and tris(hydroxymethyl)aminomethane (TRIS) are
      catalytically inactive. Where reactions proceed, the products are demetalated
      TAMLs and iron species of variable composition. Pseudo-first-order rate constants
      for the demetalation (kobs) are linear functions of the acid concentrations, and
      the effective second-order rate constants k1,eff have a hyperbolic dependence on
      [H+] (k1,eff = a1[H+]/(b1+[H+]). The rate of demetalation of 1a in H2PO4-/HPO42-
      buffer is appreciable, but the kobs values for 1b and 1c are immeasurably low,
      showing that the rates are strongly affected by the CR2 or "tail" fragments,
      which are known to potently affect the TAML basicity. The reactivities of 1
      depend insignificantly on the aromatic ring or "head" group of 1. The proposed
      mechanism involves precoordination of the acidic buffer species followed by
      hydrolysis. The demetalating abilities of buffer species depend on their
      structures and acidities. Thus, although pyridine-2-carboxylic (picolinic) acid
      catalyzes the demetalation, its 3- and 4-isomers (nicotinic and isonicotininc
      acids) are inactive. The difference is rationalized to result from the ability
      that only coordinated picolinic acid has to deliver a proton to an amidato
      nitrogen in an intramolecular manner. The reaction order in picolinic acid equals
      one for 1a and two for 1b. For 1b, "inactive" pyridine and nicotinic acid speed
      up the demetalation in the presence of picolinic acid, suggesting that the second
      order arises from the axial binding of two pyridine molecules, one of which must
      be picolinic acid. The binding of pyridine- and imidazole-type ligands was
      confirmed by UV/vis equilibrium measurements and X-ray crystallography. The
      implications of these mechanistic findings for designing superior Fe-TAML
      oxidation catalysts and catalyst formulations are discussed using the results of
      DFT calculations.

PMID- 18335939
TI  - Cyclic peptide inhibitors of staphylococcal virulence prepared by Fmoc-based
      thiolactone peptide synthesis.
AB  - Virulence factor production in Staphylococcus aureus is largely under the control
      of the accessory gene regulator (agr) quorum sensing system. There are four agr
      groups, all of which exhibit bacterial interference: each agr type synthesizes a
      cyclic autoinducing peptide (AIP) with a distinct sequence that activates its
      cognate AgrC receptor and inhibits activation of others. To better understand
      inhibitory AIP-AgrC interactions, we aimed to identify the minimal molecular
      determinants required to inhibit both non-cognate and cognate receptors. This
      minimization of the AIP pharmacophore also may have therapeutic relevance as the
      use of native AIPs to block virulence of non-cognate agr strains can prevent the
      establishment of an infection in vivo. We synthesized and evaluated the
      inhibitory activities of 10 AIP derivatives based on a truncated AIP analogue
      that inhibits all four agr types. To carry out the rapid, parallel synthesis of
      these peptides, we employed a new linker for Fmoc-based thioester peptide
      synthesis. Our results identify key structural elements that are necessary for
      AgrC inhibition and reveal key differences between non-cognate and cognate
      inhibitory requirements.

PMID- 18335940
TI  - Light-controlled supramolecular helicity of a liquid crystalline phase using a
      helical polymer functionalized with a single chiroptical molecular switch.
AB  - Control over the preferred helical sense of a poly(n-hexyl isocyanate) (PHIC) by
      using a single light-driven molecular motor, covalently attached at the polymer's
      terminus, has been accomplished in solution via a combination of photochemical
      and thermal isomerizations. Here, we report that after redesigning the
      photochromic unit to a chiroptical molecular switch, of which the two states are
      thermally stable but photochemically bistable, the chiral induction to the
      polymer's backbone is significantly improved and the handedness of the helical
      polymer is addressable by irradiation with two different wavelengths of light.
      Moreover, we show that the chiral information is transmitted, via the
      macromolecular level of the polyisocyanate, to the supramolecular level of a
      lyotropic cholesteric liquid crystalline phase consisting of these stiff, rodlike
      polymers. This allows the magnitude and sign of the supramolecular helical pitch
      of the liquid crystal film to be fully controlled by light.

PMID- 18335941
TI  - Stereoretentive synthesis and chemoselective amide-forming ligations of C
      terminal peptide alpha-ketoacids.
AB  - C-Terminal peptide cyanosulfur ylides are readily converted to C-terminal peptide
      alpha-ketoacids, poised for chemoselective amide-forming reactions with
      hydroxylamines. These easily prepared and bench stable ylides are quickly and
      selectively oxidized with aqueous Oxone without the need for protection of most
      peptide side chains and with minimal epimerization. This approach offers the
      first method for preparing enantiomerically enriched, side chain unprotected
      alpha-ketoacids.

PMID- 18335942
TI  - Site-specific prodrug release using visible light.
AB  - Using a photosensitization-singlet oxygenation-dioxetane cleavage strategy, a
      photodynamic prodrug system has been developed, whereby drugs bearing carbonyl
      groups can first be attached to a photosensitizer to give a photosensitizer-drug
      complex and then released from the complex upon visible light irradiation.
      Visible light, which has good penetration through tissue, generates singlet
      oxygen via the photosensitizer, which then releases the prodrug when and where
      required. With this system, drug mimics and methyl esters of NSAIDs have been
      successfully incorporated with photosensitizers related to verteporfin and then
      released by visible light illumination in high to quantitative yields within
      minutes.

PMID- 18335943
TI  - Reactivity of mononuclear alkylperoxo copper(II) complex. O-O bond cleavage and C
      H bond activation.
AB  - A detailed reactivity study has been carried out for the first time on a new
      mononuclear alkylperoxo copper(II) complex, which is generated by the reaction of
      copper(II) complex supported by the bis(pyridylmethyl)amine tridentate ligand
      containing a phenyl group at the 6-position of the pyridine donor groups and
      cumene hydroperoxide (CmOOH) in CH3CN. The cumylperoxo copper(II) complex thus
      obtained has been found to undergo homolytic cleavage of the O-O bond and induce
      C-H bond activation of exogenous substrates, providing important insights into
      the catalytic mechanism of copper monooxygenases.

PMID- 18335944
TI  - Room-temperature Suzuki-Miyaura couplings in water facilitated by nonionic
      amphiphiles.
AB  - Use of a dilute aqueous solution containing a nonionic amphiphile allows
      efficient Suzuki-Miyaura cross-couplings of arylboronic acids with a wide array
      of aryl halides and pseudohalides, including sterically hindered and lipophilic
      substrates, in most cases at room temperature.

PMID- 18335945
TI  - Heck couplings at room temperature in nanometer aqueous micelles.
AB  - A nonionic amphiphile such as Triton X-100 or the vitamin E-based PTS, both of
      which form nanomicelles in water, promotes Heck cross-couplings of non-water
      soluble partners at ambient temperatures. These are the first examples of Heck
      reactions conducted in water (as the only solvent) at room temperature.

PMID- 18335946
TI  - Synthesis of water-soluble poly(p-phenyleneethynylene) in neat water under
      aerobic conditions via Suzuki-Miyaura polycondensation using a diborylethyne
      synthon.
AB  - We report the synthesis, structure, and characterization of a novel ethyne
      synthon, 1,2-bis(4',4',5',5'-tetramethyl[1',3',2']dioxaborolan-2'-yl)ethyne
      (B2C2). We demonstrate the utility of B2C2 in the Suzuki-Miyaura polycondensation
      reaction, synthesizing a water-soluble poly(p-phenyleneethynylene) from [2,5
      diiodo-1,4-bis(3-propoxy-sulfonicacid)benzene] sodium salt in neat water under an
      aerobic atmosphere.

PMID- 18335947
TI  - Olefin cross-metathesis reactions at room temperature using the nonionic
      amphiphile "PTS": just add water.
AB  - The first examples of unsymmetrical olefin cross-metathesis reactions in water,
      involving water-insoluble substrates, at room temperature and using commercially
      available catalysts are reported. The key to success is to include small
      percentages of the nonionic, vitamin E-based amphiphile "PTS". The nanometer
      micelles formed accommodate water-insoluble substrates, along with a readily
      available Ru-based metathesis catalyst. Reactions proceed at ambient temperatures
      with high efficiency and very high E-selectivity, and products are easily
      isolated.

PMID- 18335948
TI  - A dearomatizing, thionium ion cyclization for the synthesis of functionalized,
      azaspirocyclic cyclohexadienones.
AB  - Thionium ions, generated by the addition of thiols to N-benzylglyoxamides,
      undergo a dearomatizing spirocyclization. The alkyl or arylsulfanyl group
      introduced during the thionium ion cyclization can act as a synthetic handle and
      a stereochemical control element during modifications of the azaspirocyclic
      frameworks (R(F) = CH(2)CH(2)C(8)F(17)).

PMID- 18335949
TI  - Total synthesis of (+/-)-mersicarpine.
AB  - The first total synthesis of the indole alkaloid mersicarpine is reported. Key
      steps include a beta-dicarbonyl radical cyclization, as well as an oxidation of
      the benzopyrrole moiety to establish the masked 1,2-dicarbonyl functionality. An
      X-ray crystal structure and discussion of the 1H NMR behavior of the natural
      product are also presented.

PMID- 18335950
TI  - Synthesis and structure of 1,4-dipiperazino benzenes: chiral terphenyl-type
      peptide helix mimetics.
AB  - The terphenyl structure has been proven to be an ideal scaffold mimicking side
      chain functionalities of peptidic alpha-helices. The synthesis of 1,4
      dipiperazino benzenes, using stepwise transition metal-catalyzed N-arylation of
      chiral piperazines to a central benzene core is reported. The structure
      determination by X-ray crystallography reveals a geometrical arrangement of the
      hydrophobic side chains resembling the orientation of key i, i + 3, and i + 7
      positions in a peptidic alpha-helix or in terphenyl helix mimetics.

PMID- 18335951
TI  - Aziridination of aliphatic alkenes catalyzed by N-heterocyclic carbene copper
      complexes.
AB  - A copper-catalyzed aziridination of aliphatic alkenes promoted by N-heterocyclic
      carbene ligands is described. The readily available catalyst IPrCu(DBM) can
      catalyze aziridination of a variety of aliphatic alkenes using alkenes as the
      limiting reagents.

PMID- 18335952
TI  - Scale-up of Agrobacterium-mediated transient protein expression in bioreactor
      grown Nicotiana glutinosa plant cell suspension culture.
AB  - The reporter gene beta-glucuronidase was transiently expressed in a 51-L
      bioreactor-grown plant cell suspension culture of Nicotiana glutinosa at a yield
      of approximately 1.1 mg through co-culture with an auxotrophic strain of
      Agrobacterium tumefaciens. The three order of magnitude scale-up involved the
      investigation of factors contributing to transient expression including the
      timing of Agrobacterium inoculation relative to the plant cell growth phase,
      plant tissue culture hormonal triggers and plant cell cycle synchronization. The
      co-culture process was simplified to facilitate implementation in a pilot-scale
      bioreactor. At the shake flask scale it was determined that elevated
      concentrations of oxygen in the headspace were detrimental to transient
      expression levels and the addition of acetosyringone to the co-culture had a
      negligible effect. The bacterial preparation process was also streamlined,
      permitting the direct transfer of the Agrobacterium culture from a bench-scale
      fermentor to the pilot-scale plant cell culture bioreactor. Increasing expression
      levels and overcoming batch-to-batch variability despite extensive procedure
      systemization remain the major technical hurdles.

PMID- 18335953
TI  - Toward development of artificial viruses for gene therapy: a comparative
      evaluation of viral and non-viral transfection.
AB  - Problems related to the safety and efficacy of gene therapies have checked the
      enthusiasm once surrounding this field, though it remains a promising approach
      for the treatment of numerous diseases. Despite the high transfection
      efficiencies attainable using viral vectors, manufacturing difficulties, safety
      concerns, and limitations related to targeting and plasmid size have prompted
      considerable research into the development of non-viral vectors. Non-viral
      vectors demonstrate low toxicity, low immunogenicity, and ease of manufacture.
      However, they have not yet achieved the transfection efficiencies displayed by
      viruses. The inability to explain or predict transfection efficiencies results,
      in part, from insufficient understanding of the intracellular processes involved
      in gene delivery. Increasingly, research has been undertaken to probe the
      processes involved in overcoming the major obstacles to vector-mediated
      transfection: (1) internalization, (2) intracellular trafficking, (3) escape to
      the cytosol, (4) nuclear translocation, and (5) gene transcription/expression.
      This paper reviews and compares the pathways and techniques involved in
      successful viral and non-viral transfection. In addition, this review provides
      evidence that non-viral vector development has been pursued successfully thus
      far, producing systems capable of evading almost all major obstacles to
      transfection. Evaluating the abilities of non-viral and viral vectors to overcome
      specific cellular barriers reveals that the greatest advantage of viral vectors
      may be related to viral DNA, which is transcribed considerably more efficiently
      than plasmid DNA. Further study in this area should enable the development of non
      viral vectors that transfect as efficiently as viral vectors.

PMID- 18335954
TI  - Biofuels from microalgae.
AB  - Microalgae are a diverse group of prokaryotic and eukaryotic photosynthetic
      microorganisms that grow rapidly due to their simple structure. They can
      potentially be employed for the production of biofuels in an economically
      effective and environmentally sustainable manner. Microalgae have been
      investigated for the production of a number of different biofuels including
      biodiesel, bio-oil, bio-syngas, and bio-hydrogen. The production of these
      biofuels can be coupled with flue gas CO2 mitigation, wastewater treatment, and
      the production of high-value chemicals. Microalgal farming can also be carried
      out with seawater using marine microalgal species as the producers. Developments
      in microalgal cultivation and downstream processing (e.g., harvesting, drying,
      and thermochemical processing) are expected to further enhance the cost
      effectiveness of the biofuel from microalgae strategy.

PMID- 18335955
TI  - Advancing biocatalysis through enzyme, cellular, and platform engineering.
AB  - Biocatalysis offers opportunities for highly selective chemical reactions with
      high turnover rates under relatively mild conditions. Use of whole-cell or multi
      enzyme systems enables transformations of complexity unmatched by nonbiological
      routes. However, advantages of biocatalysis are frequently compromised by poor
      enzymatic performance under non-native reaction conditions, the absence of
      enzymes with desired substrate or reaction specificities, and low metabolic
      fluxes or competing pathways. During the 234th National Meeting of the American
      Chemical Society, these issues were addressed in the "Advances in Biocatalysis"
      sessions. Protein engineering and metabolic pathway engineering were used to
      develop efficient enzymes and whole-cell catalysts. Novel strategies for the use
      of enzymes at solid interfaces and in nonaqueous environments were discussed, and
      efficient biotransformation platforms were demonstrated. These advances broaden
      the applications of biocatalysis in biofuels, pharmaceuticals, fine chemicals,
      and human health.

PMID- 18335956
TI  - Liposomal encapsulation of yeast alcohol dehydrogenase with cofactor for
      stabilization of the enzyme structure and activity.
AB  - Yeast alcohol dehydrogenase (YADH) with its cofactor nicotinamide adenine
      dinucleotide (NAD+) could be stably encapsulated in liposomes composed of POPC (1
      palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine). The YADH- and NAD+-containing
      liposomes (YADH-NADL) were 100 nm in mean diameter. The liposomal YADH and NAD+
      concentrations were 2.3 mg/mL and 3.9 mM, respectively. A synergistic effect of
      the liposomal encapsulation and the presence of NAD+ was examined on the thermal
      stability of YADH at 45 and 50 degrees C. The enzyme stability of the YADH-NADL
      was compared to the stabilities of the liposomal YADH (YADHL) containing 3.3
      mg/mL YADH without NAD+ as well as the free YADH with and without NAD+. Free YADH
      was increasingly deactivated during its incubation at 45 degrees C for 2 h with
      decrease of the enzyme concentration from 3.3 to 0.01 mg/mL because of the
      dissociation of tetrameric YADH into its subunits. At that temperature, the
      coexistence of free NAD+ at 3.9 mM improved the stability of free YADH at 2.3
      mg/mL through forming their thermostable complex, although the stabilization
      effect of NAD+ was lowered at 50 degrees C. The turbidity measurements for the
      above free YADH solution with and without NAD+ revealed that the change in the
      enzyme tertiary structure was much more pronounced at 50 degrees C than at 45
      degrees C even in the presence of NAD+. This suggests that YADH was readily
      deactivated in free solution due to a decrease in the inherent affinity of YADH
      with NAD+. On the other hand, both liposomal enzyme systems, YADH-NADL and YADHL,
      showed stabilities at both 45 and 50 degrees C much higher than those of the
      above free enzyme systems, YADH/NAD+ and YADH. These results imply that the
      liposome membranes stabilized the enzyme tertiary and thus quaternary structures.
      Furthermore, the enzyme activity of the YADH-NADL showed a stability higher than
      that of the YADHL with a more remarkable effect of NAD+ at 50 degrees C than at
      45 degrees C. This was considered to be because even at 50 degrees C the
      stabilization effect of lipid membranes on the tertiary and quaternary structures
      of the liposomal YADH allowed the enzyme to form its thermostable complex with
      NAD+ in liposomes.

PMID- 18335957
TI  - Synthesis and stereochemistry of long-chain quinoxaline metallocyclophanes.
AB  - Condensation of 1,2-diamino-4,5-bis(n-alkoxy)arenes with an oligopyridyl-type
      alpha-diketone afforded a series of long-chain pyridine-quinoxaline hybrids.
      These were evaluated for their ability to self-assemble with tetrahedral Cu(I)
      and Ag(I) to form dimeric, double-decker amphiphillic complexes having a
      flattened metallocyclophane topology. Detailed NOESY and T1 relaxation time
      experimentation showed that the configuration of the dicopper(I) complexes
      corresponds to inversion (meso) symmetry, which leads to an extended molecular
      shape, wherein the alkoxy chains of the individual ligand components lie on
      opposite sides of the metallocyclophane core, as opposed to the same side.
      Preliminary measurements show that the disilver(I) complexes having nC12H25 and
      nC18H37 chains exhibit reversible melting processes and undergo two endothermic
      transitions each, at 189/237 and 59/80 degrees C, respectively.

PMID- 18335958
TI  - Novel C2-symmetric macrocycles bearing diamide-diester groups: synthesis and
      enantiomeric recognition for primary alkyl ammonium salts.
AB  - We synthesized a series of novel macrocycles with diamide-diester groups (S,S)-1,
      (S,S)-2, (S,S)-3, and (R,R)-1, derived from dimethyloxalate and amino alcohols by
      high dilution technique, and evaluated enantiomeric recognition properties of
      these macrocycles toward primary alkyl ammonium salts by 1H NMR titration. Taking
      into account the host employed, important differences were observed in the Ka
      values of (R)-Am and (S)-Am for (S,S)-1 and (R,R)-1 hosts, KS/KR = 5.55 and KR/KS
      = 3.65, Delta Delta Go = 0.43 and -0.32 kJ mol-1, respectively. There seems a
      general tendency for the host to include the guests with the same absolute
      configuration.

PMID- 18335959
TI  - New building block for polyhydroxylated piperidine: total synthesis of 1,6
      dideoxynojirimycin.
AB  - (3R,4S)-3-Hydroxy-4-N-allyl-N-Boc-amino-1-pentene 10, an important precursor for
      the synthesis of polyhydroxylated piperidines, has been achieved as a single
      diastereomer without racemization via vinyl Grignard addition to N-Boc-N-allyl
      aminoaldehyde 9, which was derived from an enantiopure natural amino acid. Having
      forged a tetrahydropyridine ring scaffold 13 from 10 in 85% yield via RCM using
      Grubbs II catalyst, we were able to effect its stereodivergent dihydroxylation,
      via a common epoxide intermediate to yield a range of interesting hydroxylated
      piperidines, including ent-1,6-dideoxynojirimycin (ent-1,6-dDNJ) 1 (28% overall
      yield) and 5-amino-1,5,6-trideoxyaltrose 2 (29% over all yield) in excellent dr.
      To the best of our knowledge, our synthesis of ent-1,6-dDNJ 1 is the most
      expeditious to date.

PMID- 18335960
TI  - Multiple homo- and hetero-functionalizations of alpha-cyclodextrin through
      oriented deprotections.
AB  - Introduction of one or more functions on a cyclodextrin in a regioselective
      manner is a complex task. The discovery of a blueprint strategy involving
      regioselective deprotection reactions of fully protected cyclodextrins, instead
      of functionalization of native cyclodextrins, allowed us to propose an efficient
      alternative to reach this goal. In this paper, we have applied previously
      delineated strategies, based on steric decompression, to duplicate our
      deprotection reaction, using a combination of mono- or di-deprotections to access
      cyclodextrins with two, three and five points of attachment for one, two or three
      different new functions. The patterns of multi-functionalization delineated here
      are not accessible by any other methods. Indeed, it is the first time ever a
      cyclodextrin bearing four different groups is synthesized in a completely
      controlled manner. This work paves the way to the use of cyclodextrins as multi
      functional macrocyclic scaffolds, a use they have long been meant for, but lack
      of reliable functionalization methods hindered this development.

PMID- 18335961
TI  - Conformational properties, chiroptical spectra, and molecular self-assembly of
      2,3-piperazinodiones and their dithiono analogues.
AB  - A family of chiral cyclic oxamides was prepared by the condensation of optically
      active 1,2-diamines with diethyl oxalate. Thionation of the products with
      Lawesson's reagent afforded a series of chiral 2,3-piperazinedithiones. Molecular
      geometries of the title compounds were studied with the use of quantum mechanical
      DFT calculations and were compared to the X-ray crystallographic results. The
      heterocyclic six-membered ring adopted a half-chair conformation with the C-5
      substituent preferably at the equatorial position, whereas a substitution at the
      nitrogen atoms resulted in domination of the axial form in the conformational
      equilibrium. The opposite helicity of the twisted oxamide chromophore in the
      axial and equatorial conformers led to the opposite signs of the Cotton effects
      corresponding to two pi-pi* electronic transitions. The CD signs can be predicted
      by a simple helicity rule. The same rule is valid for 2,3-piperazinodithiones,
      where a substitution of sulfur for oxygen in the carbonyl groups results in
      bathochromic shifts of the absorption and CD bands. The crystal packing analysis
      of several 2,3-piperazinodiones revealed that strong NH...O=C intermolecular
      hydrogen-bonding interactions generating the chain motif resulted in the
      formation of 3-D networks as well as with the use of the cyclic hydrogen-bond
      motif tape structures.

PMID- 18335962
TI  - One-pot enol silane formation-Mukaiyama aldol-type addition to dimethyl acetals
      mediated by TMSOTf.
AB  - Various ketones, esters, amides, and thioesters add in high yield to dimethyl
      acetals in the presence of silyl trifluoromethanesulfonates and an amine base.
      Acetals derived from aryl, unsaturated, and aliphatic aldehydes are all effective
      substrates. The reaction proceeds in a single reaction flask, with no
      purification of the intermediate enol silane necessary.

PMID- 18335963
TI  - Regioselective palladium cross-coupling of 2,4-dihalooxazoles: convergent
      synthesis of trisoxazoles.
AB  - A regioselective Suzuki-Miyaura cross-coupling of 2,4-dihalooxazoles followed by
      a Stille coupling has been successfully developed. The procedure affords
      convergent syntheses of trisoxazoles in high yield and in a minimum number of
      steps.

PMID- 18335964
TI  - Relation between packing density and thermal transitions of alkyl chains on
      layered silicate and metal surfaces.
AB  - Self-assembled layers of alkyl chains grafted onto the surfaces of layered
      silicates, metal, and oxidic nanoparticles are utilized to control interactions
      with external media by tuning the packing density of the chains on the surface,
      head group functionality, and chain length. Characterization through experiment
      and simulation shows that the orientation of the alkyl layers and reversible
      phase transitions on heating are a function of the cross-sectional area of the
      alkyl chains in relation to the available surface area per alkyl chain. On even
      surfaces, a packing density less than 0.2 leads to nearly parallel orientation of
      the alkyl chains on the surface, a high degree of conformational disorder, and no
      reversible melting transitions. A packing density between 0.2 and 0.75 leads to
      intermediate inclination angles, semicrystalline order, and reversible melting
      transitions on heating. A packing density above 0.75 results in nearly vertical
      alignment of the surfactants on the surface, a high degree of crystalline
      character, and absence of reversible melting transitions. Curved surfaces can be
      understood by the same principle, taking into account a local radius of curvature
      and a distance-dependent packing density on the surface. In good approximation,
      this simple model is independent from the length of the alkyl chains (a minimum
      length of C10 is required to form sufficiently distinctive patterns), the
      chemical nature of the surface, and of the surfactant head group. These
      structural details primarily determine the functionality of alkyl modified
      surfaces and the temperature of thermal transitions.

PMID- 18335965
TI  - 2D self-organization of core/shell Co(hcp)/Co nanocrystals.
AB  - In this paper we report the preparation of ordered hexagonal 2D arrays of
      core/shell Cohcp/CoO nanocrystals. A full structural investigation has been
      carried out using high-resolution transmission electron microscopy, electron
      diffraction, and electron energy-loss spectroscopy.

PMID- 18335966
TI  - Evaluation of interaction forces between profilin and designed peptide probes by
      atomic force microscopy.
AB  - We evaluated the binding affinity of peptide probes for profilin (protein) using
      force curve measurement techniques and atomic force microscopy (AFM). The peptide
      probes designed and synthesized for this investigation were H-A3GP5GP5GP5G-OH
      (1), H-A3GP5G-OH (2), H-A3G7-OH (3), and H-A3G-OH (4). Each peptide probe was
      immobilized on a cantilever tip, and the interaction force to profilin,
      immobilized on a mica substrate, was examined by force curve measurements. The
      retraction forces obtained showed a sequence-dependent affinity of the peptide
      probe for profilin. The retraction force for peptide probe 1 was the largest of
      the four probes examined, and it confirmed that peptide probe 1 has high affinity
      for profilin. The single molecular retraction force between peptide probe 1 and
      profilin was estimated to be 96 pN, as determined by Gaussian fitting to the
      histogram of the retraction forces.

PMID- 18335967
TI  - A single-dipole model of surface relief grating formation on azobenzene polymer
      films.
AB  - A new model that keeps track of the dynamics of single dipoles is suggested for
      the photoinduced formation of a surface relief grating on azobenzene polymer
      films by two optical fields. Interfering optical fields provide a single dipole
      of an azobenzene molecule with two dynamical resources: rotation of the molecule
      caused by the torque, leading to an induced dipole, and its subsequent migration
      because of the electric force. Explicit development of the induced dipole of the
      molecule and its real-time migration, which depend on the details of the optical
      fields such as polarization and wavelength, can be understood self-consistently
      within the model.

PMID- 18335968
TI  - Simple fabrication of metallic colloidal doublets having electrical connectivity.
AB  - A method is described for fabricating metallic colloidal doublets of gold-gold,
      silver-silver, and gold-silver. Individual gold and silver spheres of micrometer
      diameter were synthesized by the aggregation of nanoparticles. Then, by
      controlling aggregation using ionic strength, yields of doublets above 20% were
      obtained by the salting-quenching technique. The gold-gold and silver-silver
      homodoublets were very stable mechanically, even in sonication; the gold-silver
      heterodoublets were slightly less stable than the homodoublets in sonication.
      Electrical connectivity between the gold-silver heterodoublets was verified by
      observing the autoelectrophoresis of gold-silver doublets in 3% hydrogen peroxide
      solution. The generality of the salting out and quenching technique is
      demonstrated here, and the finding that the particles are electrically connected
      will be of great significance in a number of applications.

PMID- 18335969
TI  - Quantum dot self-assembly for protein detection with sub-picomolar sensitivity.
AB  - A novel approach to sensitive and rapid antigen detection is described. In the
      presence of a specific antigen, quantum dot-antibody conjugates rapidly self
      assemble into agglomerates that are typically more than 1 order of magnitude
      larger than their individual components. The size distribution of the
      agglomerated colloids depends on, among other things, the relative concentration
      of quantum dot conjugates and antigen molecules. Quantum dot agglomerates
      mediated by antigen recognition were characterized by measuring their light
      scattering and fluorescence characteristics in an unmodified flow cytometer.
      Protein antigens angiopoietin-2 and mouse IgG were detected to sub-picomolar
      concentrations using this method. This simple technique enables the potential
      simultaneous detection of multiple antigenic biomarkers directly from
      physiological media and could be used for early detection and frequent screening
      of cancers and other diseases.

PMID- 18335970
TI  - Controllable preparation of nanoparticles by drops and plugs flow in a
      microchannel device.
AB  - Well controlled two-liquid-phase flows in a T-junction microchannel device have
      been realized. The system of H2SO4 and BaCl2, respectively, in two phases to form
      BaSO4 nanoparticles was used as a probe to characterize the microscale two-phase
      flow and transport conditions of a system with interphase mass transfer and
      chemical reaction. Nanoparticles with narrow size and good dispersibility were
      produced through drops or plugs flow in the microdevice. As a novel work, the
      influence of mass transfer and chemical reaction on interfacial tension and flow
      patterns was discussed based on the experiments. At the same time, the effect of
      the two-phase flow patterns on the nanoparticle size was also discussed. It was
      found that the increase of the amount of mass transfer and chemical reaction
      could change the flow patterns from plugs flow to drops flow. The drop diameter
      or plug length could be changed in a wide range. Accordingly, a new parameter of
      mu(0)u(c)/gamma(0)/Q(d) was defined to distinguish the flow patterns. The
      prepared nanoparticles ranged in size from 10 to 40 nm. Apparently, the particle
      size decreased with the increase of the drop diameter or plug length. Reasons
      were discussed based on the mass transfer direction and speed in drops and plugs
      flow patterns.

PMID- 18335972
TI  - Nanoalloys: from theory to applications of alloy clusters and nanoparticles.

PMID- 18335974
TI  - 5-tert-butyl-N-pyrazol-4-yl-4,5,6,7-tetrahydrobenzo[d]isoxazole-3-carboxamide
      derivatives as novel potent inhibitors of Mycobacterium tuberculosis pantothenate
      synthetase: initiating a quest for new antitubercular drugs.
AB  - Pantothenate synthetase (PS) is one of the potential new antimicrobial targets
      that may also be useful for the treatment of the nonreplicating persistent forms
      of Mycobacterium tuberculosis. In this Letter we present a series of 5- tert
      butyl- N-pyrazol-4-yl-4,5,6,7-tetrahydrobenzo[ d]isoxazole-3-carboxamide
      derivatives as novel potent Mycobacterium tuberculosis PS inhibitors, their in
      silico molecular design, synthesis, and inhibitory activity.

PMID- 18335975
TI  - Pharmacological exploitation of the peroxisome proliferator-activated receptor
      gamma agonist ciglitazone to develop a novel class of androgen receptor-ablative
      agents.
AB  - On the basis of our finding that the peroxisome proliferator-activated receptor
      gamma (PPARgamma) agonist ciglitazone at high doses was able to mediate PPARgamma
      independent transcriptional repression of androgen receptor (AR) in a tumor cell
      specific manner, we used Delta2CG, a PPARgamma-inactive analogue of ciglitazone,
      to conduct lead optimization to develop a novel class of AR-ablative agents.
      Structure-activity analysis indicates a high degree of flexibility in realigning
      Delta2CG's structural moieties without compromising potency in AR repression, as
      evidenced by the higher AR-ablative activity of the permuted isomer 9 [( Z)-5-(4
      hydroxybenzylidene)-3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione]. Further
      modifications of 9 gave rise to 12 [( Z)-5-(4-hydroxy-3
      trifluoromethylbenzylidene)-3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione],
      which completely inhibited AR expression in LNCaP cells at low micromolar
      concentrations. This AR down-regulation led to growth inhibition in LNCaP cells
      through apoptosis induction. Moreover, the role of AR repression in the
      antiproliferative effect of compound 12 was validated by the differential
      inhibition of cell viability between androgen-responsive and androgen
      nonresponsive cells.

PMID- 18335976
TI  - Benzodioxoles: novel cannabinoid-1 receptor inverse agonists for the treatment of
      obesity.
AB  - The application of the evolutionary fragment-based de novo design tool TOPology
      Assigning System (TOPAS), starting from a known CB1R (CB-1 receptor) ligand,
      followed by further refinement principles, including pharmacophore compliance,
      chemical tractability, and drug likeness, allowed the identification of
      benzodioxoles as a novel CB1R inverse agonist series. Extensive multidimensional
      optimization was rewarded by the identification of promising lead compounds,
      showing in vivo activity. These compounds reversed the CP-55940-induced
      hypothermia in Naval Medical Research Institute (NMRI) mice and reduced body
      weight gain, as well as fat mass, in diet-induced obese Sprague-Dawley rats.
      Herein, we disclose the tools and strategies that were employed for rapid hit
      identification, synthesis and generation of structure-activity relationships,
      ultimately leading to the identification of (+)-[( R)-2-(2,4-dichloride-phenyl)-6
      fluoro-2-(4-fluoro-phenyl)-benzo[1,3]dioxol-5-yl]-morpholin-4-yl-methanone ( R)
      14g . Biochemical, pharmacokinetic, and pharmacodynamic characteristics of ( R)
      14g are discussed.

PMID- 18335977
TI  - Quantifying the relationships among drug classes.
AB  - The similarity of drug targets is typically measured using sequence or structural
      information. Here, we consider chemo-centric approaches that measure target
      similarity on the basis of their ligands, asking how chemoinformatics
      similarities differ from those derived bioinformatically, how stable the ligand
      networks are to changes in chemoinformatics metrics, and which network is the
      most reliable for prediction of pharmacology. We calculated the similarities
      between hundreds of drug targets and their ligands and mapped the relationship
      between them in a formal network. Bioinformatics networks were based on the BLAST
      similarity between sequences, while chemoinformatics networks were based on the
      ligand-set similarities calculated with either the Similarity Ensemble Approach
      (SEA) or a method derived from Bayesian statistics. By multiple criteria,
      bioinformatics and chemoinformatics networks differed substantially, and only
      occasionally did a high sequence similarity correspond to a high ligand-set
      similarity. In contrast, the chemoinformatics networks were stable to the method
      used to calculate the ligand-set similarities and to the chemical representation
      of the ligands. Also, the chemoinformatics networks were more natural and more
      organized, by network theory, than their bioinformatics counterparts: ligand
      based networks were found to be small-world and broad-scale.

PMID- 18335978
TI  - Generation of new synthetic scaffolds using framework libraries selected and
      refined via medicinal chemist synthetic expertise.
AB  - With the expansion in the application of library methods in medicinal chemistry
      and chemical biology there is a growing need for improved technology for the
      design of novel templates that are well suited for the synthesis of libraries
      targeted toward specific subsets of protein families. In this report, we
      delineate an improved stepwise general method that is well suited for this
      purpose. This process uses virtual framework libraries to identify frameworks
      that rigidly match specific aspects of a ligand's bioactive conformation. The
      resulting frameworks can then be ranked and sequentially modified by a
      combination of computational scripts and human derived expertise, in order to
      develop rational proposals for new combinatorial templates or new sets of
      potential ligands.

PMID- 18335979
TI  - Binuclear iron carbonyl nitrosyls: bridging nitrosyls versus bridging carbonyls.
AB  - The iron carbonyl nitrosyls Fe 2(NO) 2(CO) n ( n = 7, 6, 5, 4, 3) have been
      studied by density functional theory (DFT) using the B3LYP and BP86 methods, for
      comparison of their predicted structures with those of isoelectronic cobalt
      carbonyl derivatives. The lowest energy structures for Fe 2(NO) 2(CO) 7 and Fe
      2(NO) 2(CO) 6 have two NO bridges, and the lowest energy structure for Fe 2(NO)
      2(CO) 5 has a single NO bridge with metal-metal distances (BP86) of 3.161, 2.598,
      and 2.426 A, respectively, corresponding to the formal metal-metal bond orders of
      zero, one, and two, respectively, required for the favored 18-electron
      configuration for the iron atoms. The heptacarbonyl Fe 2(NO) 2(CO) 7 is
      thermodynamically unstable with respect to CO loss to give Fe 2(NO) 2(CO) 6. The
      favored structures for the more highly unsaturated Fe 2(NO) 2(CO) 4 and Fe 2(NO)
      2(CO) 3 also have bridging NO groups but avoid iron-iron bond orders higher than
      two by formal donation of five electrons from bridging NO groups with relatively
      short Fe-O distances. The lowest energy structures of the unsaturated Fe 2(NO)
      2(CO) n derivatives ( n = 5, 4, 3) are significantly different from the
      isoelectronic cobalt carbonyls Co 2(CO) n +2 owing to the tendency for Fe 2(NO)
      2(CO) n to form structures with bridging NO groups and metal-metal formal bond
      orders no higher than two.

PMID- 18335973
TI  - Carbonic anhydrase as a model for biophysical and physical-organic studies of
      proteins and protein-ligand binding.

PMID- 18335980
TI  - Selectivity of thiolate ligand and preference of substrate in model reactions of
      dissimilatory nitrate reductase.
AB  - Complexes analogous to the active site of dissimilatory nitrate reductase from
      Desulfovibrio desulfuricans are synthesized. The hexacoordinated complexes [PPh
      4][Mo (IV)(PPh 3)(SR)(mnt) 2] (R = -CH 2CH 3 ( 1), -CH 2Ph ( 2)) released PPh 3
      in solution to generate the active model cofactor, {Mo (IV)(SR)(mnt) 2} (1-),
      ready with a site for nitrate binding. Kinetics for nitrate reduction by the
      complexes 1 and 2 followed Michaelis-Menten saturation kinetics with a faster
      rate in the case of 1 ( V Max = 3.2 x 10 (-2) s (-1), K M = 2.3 x 10 (-4) M) than
      that reported earlier ( V Max = 4.2 x 10 (-3) s (-1), K M = 4.3 x 10 (-4) M) (
      Majumdar, A. ; Pal, K. ; Sarkar, S. J. Am. Chem. Soc. 2006, 128, 4196- 4197 ).
      The oxidized molybdenum species may be reduced back by PPh 3 to the starting
      complex, and a catalytic cycle involving [Bu 4N][NO 3] and PPh 3 as the oxidizing
      and reducing substrates, respectively, is established with the complexes 1 and 2.
      Isostructural complexes, [Et 4N][Mo (IV)(PPh 3)(X)(mnt) 2] (X = -Br ( 3), -I (
      4)) did not show any reductive activity toward nitrate. The selectivity of the
      thiolate ligand for the functional activity and the cessation of such activity in
      isostructural halo complexes demonstrate the necessity of thiolate coordination.
      Electrochemical data of all these complexes correlate the ability of the
      thiolated species for such oxotransfer activity. Compounds 1 and 2 are capable of
      reducing substrates like TMANO or DMSO, but after the initial 15-20% conversion,
      the product trimethylamine or dimethylsulfide formed interacts with the active
      parent complexes 1 and 2 thereby slowing down further oxo-transfer reaction
      similar to feedback type reactions. From the functional nitrate reduction, the
      molybdenum species finally reacts with the nitrite formed leading to
      nitrosylation similar to the NO evolution reaction by periplasmic nitrate
      reductase from Pseudomonas dentrificans. All these complexes ( 1- 4) are
      characterized structurally by X-ray, elemental analysis, electrochemistry,
      electronic, FT-IR, mass and (31)P NMR spectroscopic measurements.

PMID- 18335981
TI  - Synthesis, morphology, structure, and magnetic characterization of layered cobalt
      hydroxyisocyanates.
AB  - New layered pink cobalt hydroxyisocyanates have been prepared by controlled
      hydrolysis of aqueous solutions of CoCl2.6H2O. Co(OH)(1.4)(NCO) 0.6.0.6H 2O ( 1)
      is formed when urea is used as the hydrolysis agent and mannitol as the
      stabilizer, while Co(OH)(1.25)(NCO)(0.75).0.2H2O ( 2) is formed when the
      hydrolysis agent is changed to hexamethylenetetramine and NaOCN is added to the
      solution. IR spectroscopy of 1 and 2 indicates that the OCN (-) is N-bonded to Co
      (2+). The X-ray powder data for 1 could be indexed using an intergrowth model
      consisting of both rhombohedral ( R3 m (166); a = 3.2031(1) A, c = 23.6876(11) A,
      hydrotalcite-like, 3 R 1) and hexagonal ( P 63/ mmc (194); a = 3.2005(2) A, c =
      15.8303(5) A, Manasseite-like, 2H1) polytypes. Rietveld refinement of the X-ray
      powder data was performed using a two polytype model and 30% random substitution
      of the OH (-) ions by OCN (-). Although it is less crystalline, the XRD data for
      2 can be indexed using a rhombohedral-symmetry cell with unit cell parameters, a
      = 3.158 A and c = 21.57 A. Both 1 and 2 exhibit magnetically ordered ground
      states with a saturation magnetization of ca. 2.0 mu B. The magnetization data is
      consistent with 3D ferromagnetic ordering of edge-share octahedral-Co (2+) layers
      with effective spin S' = 1/2.

PMID- 18335982
TI  - Synthesis, redox, and amphiphilic properties of responsive salycilaldimine
      copper(II) soft materials.
AB  - Hydrolysis of the asymmetric pyridine- and phenol-containing ligand HL (1) (2
      hydroxy-4-6-di- tert-butylbenzyl-2-pyridylmethyl)imine) led to the use of bis
      (3,5-di -tert-butyl-2-phenolato-benzaldehyde)copper(II), [Cu (II)(L (SAL)) 2] (
      1) as a precursor for bis-(2,4-di- tert-butyl-6-octadecyliminomethyl
      phenolato)copper(II), [Cu (II)(L (2)) 2] ( 3), bis-(2,4-di- tert-butyl-6
      octadecyl aminomethyl-phenolato)copper(II), [Cu (II)(L (2A)) 2] ( 3'), and bis
      (2,4-di- tert-butyl-6-[(3,4,5-tris-dodecyloxy-phenylimino)-methyl]
      phenolato)copper(II), [Cu (II)(L (3)) 2] ( 4). These complexes exhibit
      hydrophilic copper-containing head groups, hydrophobic alkyl and alkoxo tails,
      and present potential as precursors for redox-responsive Langmuir-Blodgett films.
      All systems were characterized by means of elemental, spectrometric,
      spectroscopic, and electrochemical techniques, and their amphiphilic properties
      were probed by means of compression isotherms and Brewster angle microscopy. Good
      redox activity was observed for 3 with two phenoxyl radical processes between 0.5
      and 0.8 V vs Fc (+)/Fc, but this complex lacks amphiphilic behavior. To attain
      good balance between redox response and amphiphilicity, increased core
      flexibility in 3' and incorporation of alkoxy chains in 4 were attempted. Film
      formation with collapse at 14 mN.m (-1) was observed for the alkoxy-derivative
      but redox-response was seriously compromised. Core flexibility improved Langmuir
      film formation with a higher formal collapse and showed excellent cyclability of
      the ligand-based processes.

PMID- 18335983
TI  - Reactivity and spectroscopy of the {Ru(DMAP)5} fragment: an {Ru(NH3)5} analogue.
AB  - Reaction of trans-Ru(DMSO)4Cl2 with DMAP (DMAP = 4-dimethylaminopyridine) yields
      the yellow [Ru(DMAP)6](2+) cation in good yield. The crystal and molecular
      structure of [Ru(DMAP)6]Cl2.6CH3CH2OH was determined by X-ray diffraction
      methods. The complex crystallizes in the trigonal R3 space group with a = b =
      16.373(1), c = 20.311(1) A, gamma = 120 degrees , and Z = 3 molecules per unit
      cell. The reaction of [Ru(DMAP)6](2+) in aerobic water gives the red
      [Ru(III)(DMAP)5(OH)](2+) cation. This complex shows a chemical behavior similar
      to [Ru(III)(NH3)5Cl](2+) and allows the preparation of a family of
      [Ru(DMAP)5L](n+) complexes. Their electronic properties indicate that the
      {Ru(II)(DMAP)5} fragment is a weaker pi-donor than {Ru(II)(NH 3)5}. Our density
      functional theory (DFT) calculations show that in {Ru(II)(DMAP)5} the DMAP
      ligands can compete for the pi electron density of the ruthenium making the
      fragment a weaker pi-donor.

PMID- 18335984
TI  - Effect of water on the catalytic oxidation of catechols.
AB  - A dinuclear copper(II) complex derived from a new water-soluble pentadentate
      Schiff base backbone ligand has been prepared and characterized in solution and
      in the solid state. The complex has been found to accelerate the aerobic
      oxidation of 3,5-di- tert-butylcatechol (DTBC) into 3,5-di- tert-butylquinone
      (DTBQ) by 5 orders of magnitude, compared to the background reaction in aqueous
      methanol (k(cat)/k(non) = 160,000) at 30 degrees C. The transformation of the
      model substrate is considerably slower in pure methanol (k(cat)/k(non) = 60,000)
      under otherwise identical conditions. In-depth investigation of the catalytically
      active species revealed different structures for the copper(II) complex in
      methanol and in methanol/water mixtures.

PMID- 18335985
TI  - Inelastic electron interaction with chloroform clusters embedded in helium
      droplets.
AB  - The inelastic electron interaction (ionization/attachment) with chloroform
      embedded in helium droplets has been studied utilizing a two-sector field mass
      spectrometer. Positive mass spectra have been recorded at the electron energy of
      70 eV and are compared with previous results in the gas phase and with other
      systems embedded in helium droplets. Moreover, the negative ion mass spectrum has
      been recorded at the electron energy of 1.5 eV. Both negative and positive mass
      spectra show that chloroform clusters are easily formed by embedding single
      molecules in the helium droplets. Moreover, for anions appearing in the mass
      spectrum, the ion yield has been determined as function of the electron energy.
      While no parent anion of chloroform can be observed in the gas phase, the present
      cluster environment allows the stabilization of the transient negative ion. The
      influence of the helium droplet upon the ionization or attachment process of the
      embedded chloroform is discussed.

PMID- 18335986
TI  - A doorway state leads to photostability or triplet photodamage in thymine DNA.
AB  - Ultraviolet irradiation of DNA produces electronic excited states that
      predominantly eliminate the excitation energy by returning to the ground state
      (photostability) or following minor pathways into mutagenic photoproducts
      (photodamage). The cyclobutane pyrimidine dimer (CPD) formed from
      photodimerization of thymines in DNA is the most common form of photodamage. The
      underlying molecular processes governing photostability and photodamage of
      thymine-constituted DNA remain unclear. Here, a combined femtosecond broadband
      time-resolved fluorescence and transient absorption spectroscopies were employed
      to study a monomer thymidine and a single-stranded thymine oligonucleotide. We
      show that the protecting deactivation of a thymine multimer is due to an
      ultrafast single-base localized stepwise mechanism where the initial excited
      state decays via a doorway state to the ground state or proceeds via the doorway
      state to a triplet state identified as a major precursor for CPD photodamage.
      These results provide new mechanistic characterization of and a dynamic link
      between the photoexcitation of DNA and DNA photostability and photodamage.

PMID- 18335987
TI  - Engineering strength, porosity, and emission intensity of nanostructured CdSe
      networks by altering the building-block shape.
AB  - The effect of primary particle shape on the porosity, mechanical strength, and
      luminescence intensity of metal chalcogenide aerogels was probed by comparison of
      CdSe aerogels prepared from spherical and rod-shaped particles. Rod-shaped
      particles yield aerogels with polymeric morphologies in contrast to the colloidal
      morphology obtained from spherical particles. Relative to the colloidal
      analogues, the polymeric CdSe aerogels exhibit twice the surface area, a doubling
      of the complex viscosity for 5 wt % aerogel-PDMS composites, and a 25-fold
      increase in emission intensity. Altering the shape of the building block from
      which nanostructured networks are assembled is an effective way to tune the basic
      properties of metal chalcogenide semiconducting aerogels.

PMID- 18335988
TI  - Large differences in secondary metal-arene interactions in the transition-metal
      dimers ArMMAr (Ar = terphenyl; M = Cr, Fe, or Co): implications for Cr-Cr
      quintuple bonding.
AB  - Quantum mechanical calculations, using both CASPT2 and DFT methods, for the model
      systems (MeMMMe, PhMMPh, (MeMMMe)(C6H6)2, Ar(S)MMAr(S), Ar (#)MMAr(#); M = Cr,
      Fe, Co; Ar(S) = C6H4-2(C6H5), Ar(#) = C6H3-2,6(C6H3-2,6-Me2)2) are described.
      These studies were undertaken to provide a multireference description of the
      metal-metal bond in the simple dimers MeMMMe and PhMMPh (M = Cr, Fe, Co) and to
      determine the extent of secondary metal-arene interaction involving the flanking
      aryl rings of the terphenyl ligands in quintuply bonded Ar'CrCrAr' (Ar' = C6H3
      2,6(C6H3-2,6-Pr(i)2)2). We show that in the Cr-Cr species the Cr-arene
      interaction is a feeble one that causes only a small weakening of the quintuple
      bond. In sharp contrast, in the analogous Fe and Co species strong eta(6)-arene
      interactions that preclude significant metal-metal bonding are predicted.

PMID- 18335989
TI  - Switching between supramolecular dimer and nonthreaded supramolecular self
      assembly of stilbene amide-alpha-cyclodextrin by photoirradiation.
AB  - 3-trans-Stilbene amide-alpha-cyclodextrin (3-trans-Sti-alpha-CD) formed a double
      threaded dimer in aqueous solutions. In contrast, the photoisomerization of the
      stilbene moiety in 3-Sti-alpha-CD from trans to cis leads to the structural
      changes from the double-threaded dimer to nonthreaded supramolecular assemblies
      in aqueous solutions. The structures of these supramolecular complexes have been
      found to be controllable by photoirradiation.

PMID- 18335990
TI  - The different photoisomerization efficiency of azobenzene in the lowest n pi* and
      pi pi* singlets: the role of a phantom state.
AB  - Azobenzene E<==>Z photoisomerization, following excitation to the bright S(pi
      pi*) state, is investigated by means of ab initio CASSCF optimizations and
      perturbative CASPT2 corrections. Specifically, by elucidating the S(pi pi*)
      deactivation paths, we explain the mechanism responsible for azobenzene
      photoisomerization, the lower isomerization quantum yields observed for the S(pi
      pi*) excitation than for the S1(n pi*) excitation in the isolated molecule, and
      the recovery of the Kasha rule observed in sterically hindered azobenzenes. We
      find that a doubly excited state is a photoreaction intermediate that plays a
      very important role in the decay of the bright S(pi pi*). We show that this
      doubly excited state, which is immediately populated by molecules excited to S(pi
      pi*), drives the photoisomerization along the torsion path and also induces a
      fast internal conversion to the S1(n pi*) at a variety of geometries, thus
      shaping (all the most important features of) the S(pi pi*) decay pathway and
      photoreactivity. We reach this conclusion by determining the critical structures,
      the minimum energy paths originating on the bright S(pi pi*) state and on other
      relevant excited states including S1(n pi*), and by characterizing the conical
      intersection seams that are important in deciding the photochemical outcome. The
      model is consistent with the most recent time-resolved spectroscopic and
      photochemical data.

PMID- 18335992
TI  - Electrogenerated chemiluminescence of a spirobifluorene-linked bisanthracene: a
      possible simultaneous, two-electron transfer.
AB  - We report the electrogenerated chemiluminescence (ECL) of 2,2'-bis(10
      phenylanthracen-9-yl)-9,9'-spirobifluorene (spiro-FPA), a dichromophoric molecule
      composed of two phenylanthracenes linked by a spirobifluorene moiety (PA-X-PA).
      The results are compared to those for 9,10-diphenylanthracene (DPA), a related
      molecule with a single chromophore. Cyclic voltammetry (CV) of spiro-FPA shows
      two reversible, closely spaced, one-electron transfers on both reduction and
      oxidation, occurring at E(o)(1,red) = -2.02, E(o)(2,red) = -2.07 V vs SCE and
      E(o)(1,ox) = 1.14, E(o)(2,ox) = 1.20 V vs SCE. The potentials for each pair are
      close enough to appear as a single peak in CV, indicating that the
      spirobifluorene moiety interrupts conjugation between the redox centers. The
      potentials observed are similar to those of DPA, which shows E(o)(red) = -2.06 V
      vs SCE and E(o)(ox) = 1.15 V vs SCE. The absorbance spectrum of spiro-FPA shows
      lambda(max,abs) = 377 nm, with 377 = 25,700 M(-1) s(-1), while DPA exhibited
      lambda(max,abs) = 374 nm, with 374 = 13,800 M(-1) s(-1), demonstrating that spiro
      FPA has twice the available chromophores as DPA. Photoluminescence (PL) data for
      spiro-FPA shows lambda(max,PL) = 434 nm, with Phi(PL) = 0.74, while DPA
      fluoresces at 420 nm with Phi(PL) = 0.91; thus, there is greater solvent or
      structural relaxation in the spiro-FPA excited state, which may account for the
      greater internal conversion. Unlike DPA, the ECL spectrum of spiro-FPA exhibits
      long-wavelength emission not observed in the PL. We attribute this emission to
      excimers formed during annihilation ECL. Steric hindrance prevents DPA from
      forming excimers, even in ECL, but spiro-FPA annihilation can occur between pairs
      of di-ions (PA(*-)-X-PA(*-) and PA(*+)-X-PA(*+)), which are electrostatically
      more strongly attracted to one another than the mono-ions. This greater
      electrostatic attraction may be sufficient to overcome the steric hindrance to
      excimer formation. Lowering the electrolyte concentration decreases the
      electrostatic shielding of the ions from one another; thus, the increase in
      longer wavelength ECL accompanying a decrease in electrolyte concentration
      supports the role of the di-ions in excimer formation. Additionally, simulations
      show, consistent with experiment, a more rapid decrease in excimer concentration
      than in excited monomer concentration as a function of time after each potential
      pulse. This is probably due to the greater number of scavenging reactions
      available for di-ions. The simulations are confirmed experimentally when lower
      potential pulsing frequencies yield lower relative excimer emission. Since an
      excited state created by one-electron transfer between two di-ions should be
      rapidly quenched via electron transfer by the other PA moiety, the existence of
      excimers suggests the possibility of simultaneous, two-electron transfer to
      generate the excimer.

PMID- 18335991
TI  - Mild synthesis of a family of planar triazinium cations via proton-assisted
      cyclization of pyridyl containing azo compounds and studies on DNA intercalation.
AB  - An efficient synthesis of a family of heteroaromatic triazinium compounds, [2a]X
      [2g]X (X = Cl, ClO4, NO3, and HSO4), from 2-(arylazo)pyridines via proton
      catalyzed heterocyclization is described. Characterization of the compounds is
      made by different spectroscopic, electrochemical techniques, as well as single
      crystal structure determination of the triflate salt of a representative
      compound, [2a]CF3SO3. The bond parameters indicate that the tricyclo compound,
      2a(+), is planar and aromatic with a N-N bond length of 1.275(6) A. These
      exhibited fluorescence with an emission maximum in the range of 540-535 nm with
      moderate quantum yields. The triazinium salts can be reduced in two successive
      one-electron steps as probed by cyclic voltammetry and coulometry. The
      paramagnetic radical intermediate 2a(*) is distinguished by a sharp and intense
      EPR spectrum. Fluorescence spectroscopy, circular dichroism, cyclic voltammetry,
      viscosity measurements, together with DNA melting studies have been used to
      characterize the binding of 2a(+) with calf thymus DNA. The emission quenching of
      the compound by [Fe(CN)6](4-) decreased when bound to DNA. As determined by a MTT
      assay, 2a(+) exhibited significant cytotoxicity at a higher concentration range
      of 1 mg/mL to 1 microg/mL; however, the % survival ratio increased with dilution.
      Cellular uptake studies of the referenced compound were followed by FACS
      analysis.

PMID- 18335993
TI  - Alterations of flavonoid biosynthesis in young grapevine (Vitis vinifera L.)
      leaves, flowers, and berries induced by the dioxygenase inhibitor prohexadione
      Ca.
AB  - Prohexadione-Ca is a structural mimic of 2-oxoglutarate, and according to this
      property, it is able to inhibit dioxygenase enzymes, which require 2-oxoglutarate
      as a cosubstrate. Such enzymes are involved in flavonoid biosynthesis; therefore,
      prohexadione-Ca treatment leads to alterations in the flavonoid metabolism in
      grapevine tissues. Because of the fact that phenolic compounds often are
      responsible for enhanced plant resistance, modification of phenylpropanoid
      metabolism using elicitation can be considered as a new potential strategy in
      plant protection. The phenolic compounds were analyzed by high-performance liquid
      chromatography combined with chemical reaction detection. Tissue treatment
      induced the accumulation of unusual flavonoids, which were identified as
      derivatives of pentahydroxyflavanone, eriodictyol, and luteoliflavan.
      Concentrations of constitutive flavonoids were also affected by the bioregulator
      treatment. The alterations of the flavonoid profiles are discussed with respect
      to substrate preferences of relevant enzymes.

PMID- 18335994
TI  - Analysis of chlorothalonil and three degradates in sediment and soil.
AB  - A method has been developed for the simultaneous extraction of chlorothalonil and
      three of its degradates (4-hydroxy-2,5,6-trichloroisophthalonitrile, 1-carbamoyl
      3-cyano-4-hydroxy-2,5,6-trichlorobenzene, and 1,3-dicarbamoyl-2,4,5,6
      tetrachlorobenzene) from soils and sediments; the compounds were extracted using
      sonication with acetone and isolation of the parent compound and matrix
      interferences from the degradates by solid phase extraction (SPE). The
      chlorothalonil fraction underwent further coextracted matrix interference removal
      with Florisil. The degradates were derivatized with N, O-bis(trimethylsilyl)
      trifluoroacetamide (BSTFA) and chlorotrimethylsilane (TMCS). All compounds were
      analyzed by gas chromatography-mass spectrometry (GC-MS). Recoveries on a spiked
      (20 and 200 microg kg (-1)) sediment ranged from 80% to 91% with calculated
      limits of detection of 1-5 microg kg (-1) dry weight sediment. An additional 20
      sediment samples were collected in watersheds from the Southeastern United States
      where chlorothalonil is used widely on peanuts and other crops. None of the
      target compounds were detected. Laboratory fortified recoveries of chlorothalonil
      and its degradates in these environmental sediment samples ranged from 75% to
      89%.

PMID- 18335995
TI  - Mechanism and inhibition of saFabI, the enoyl reductase from Staphylococcus
      aureus.
AB  - Approximately one-third of the world's population carries Staphylococcus aureus.
      The recent emergence of extreme drug resistant strains that are resistant to the
      "antibiotic of last resort", vancomycin, has caused a further increase in the
      pressing need to discover new drugs against this organism. The S. aureus enoyl
      reductase, saFabI, is a validated target for drug discovery. To drive the
      development of potent and selective saFabI inhibitors, we have studied the
      mechanism of the enzyme and analyzed the interaction of saFabI with triclosan and
      two related diphenyl ether inhibitors. Results from kinetic assays reveal that
      saFabI is NADPH-dependent, and prefers acyl carrier protein substrates carrying
      fatty acids with long acyl chains. On the basis of product inhibition studies, we
      propose that the reaction proceeds via an ordered sequential ternary complex,
      with the ACP substrate binding first, followed by NADPH. The interaction of NADPH
      with the enzyme has been further explored by site-directed mutagenesis, and
      residues R40 and K41 have been shown to be involved in determining the
      specificity of the enzyme for NADPH compared to NADH. Finally, in preliminary
      inhibition studies, we have shown that triclosan, 5-ethyl-2-phenoxyphenol (EPP),
      and 5-chloro-2-phenoxyphenol (CPP) are all nanomolar slow-onset inhibitors of
      saFabI. These compounds inhibit the growth of S. aureus with MIC values of 0.03
      0.06 microg/mL. Upon selection for resistance, three novel safabI mutations,
      A95V, I193S, and F204S, were identified. Strains containing these mutations had
      MIC values approximately 100-fold larger than that of the wild-type strain,
      whereas the purified mutant enzymes had K i values 5-3000-fold larger than that
      of wild-type saFabI. The increase in both MIC and K i values caused by the
      mutations supports the proposal that saFabI is the intracellular target for the
      diphenyl ether-based inhibitors.

PMID- 18335996
TI  - Trapping a folding intermediate of the alpha-helix: stabilization of the pi
      helix.
AB  - We report the design, synthesis, and characterization of a short peptide trapped
      in a pi-helix configuration. This high-energy conformation was nucleated by a
      preorganized pi-turn, which was obtained by replacing an N-terminal
      intramolecular main chain i and i + 5 hydrogen bond with a carbon-carbon bond.
      Our studies highlight the nucleation parameter as a key factor contributing to
      the relative instability of the pi-helix and allow us to estimate fundamental
      helix-coil transition parameters for this conformation.

PMID- 18335997
TI  - Neogenin interacts with hemojuvelin through its two membrane-proximal fibronectin
      type III domains.
AB  - Hemojuvelin is a recently identified iron-regulatory protein that plays an
      important role in affecting the expression of hepcidin, a key iron regulatory
      hormone. Although the underlying mechanism of this process is not clear, several
      hemojuvelin-binding proteins, including the cell surface receptor neogenin and
      bone morphogenetic protein (BMP) cytokines, have been identified. The ectodomain
      of neogenin is composed of four immunoglobulin-like (Ig) domains followed by six
      fibronectin type III-like (FNIII) domains. Here we report expression of soluble
      versions of hemojuvelin and neogenin for biochemical characterization of their
      interaction and the interaction of HJV with BMP-2. Hemojuvelin normally undergoes
      an autocatalytic cleavage, and as in vivo, recombinant hemojuvelin exists as a
      mixture of cleaved and uncleaved forms. Neogenin binds to cleaved and noncleaved
      hemojuvelin, as verified by its binding to an uncleaved mutant hemojuvelin. We
      localized the hemojuvelin binding site on neogenin to the membrane-proximal fifth
      and sixth FNIII domains and the juxtamembrane linker and showed that a fragment
      containing only this region binds 2-3 orders of magnitude more tightly than the
      entire neogenin ectodomain. Binding to the most membrane-proximal region of
      neogenin may play a role in regulating the levels of soluble and membrane-bound
      forms of hemojuvelin, which in turn would influence the amount of free BMP-2
      available for binding to its receptors and triggering transcription of the
      hepcidin gene. Our finding that BMP-2 and neogenin bind simultaneously to
      hemojuvelin raises the possibility that neogenin is part of a multiprotein
      complex at the hepatocyte membrane involving BMP, its receptors, and hemojuvelin.

PMID- 18335998
TI  - Semisynthesis of S-desoxybrevetoxin-B2 and brevetoxin-B2, and assessment of their
      acute toxicities.
AB  - Brevetoxins are neurotoxins associated with blooms of marine algae such as
      Karenia brevis and can accumulate in the marine food chain, causing intoxication
      of marine animals and people consuming seafood. Brevetoxin-B2 ( 5) is a toxic
      metabolite produced in shellfish exposed to algae that contain brevetoxin-B ( 1).
      S-Desoxybrevetoxin-B2 ( 4) has been proposed as a cometabolite produced during
      this transformation, and while LC-MS analyses suggest its presence in shellfish,
      it has not yet been isolated and characterized. Studies on these materials are
      severely constrained by the difficulty of obtaining and purifying them from
      natural sources. We have developed a convenient one-pot conversion of
      commercially available brevetoxin-B ( 1) into S-desoxybrevetoxin-B2 ( 4), and a
      simple method for converting 4 into brevetoxin-B2 ( 5). Full NMR and mass
      spectral characterization of 4 and 5 confirmed their structures and showed that
      the ratio of diastereoisomers in the synthetic 4 and 5 was similar to that
      observed in naturally contaminated shellfish. The LD 50 values for 4, 5, and
      dihydrobrevetoxin-B ( 6) by ip injection in mice were 211, 400, and 250
      microg/kg, respectively. The methodology for synthesis of brevetoxin metabolites
      should greatly facilitate toxicological, biochemical and immunochemical studies
      of these substances, as well as the production of analytical standards.

PMID- 18335999
TI  - Magnetic proteinase K reactor as a new tool for reproducible limited protein
      digestion.
AB  - As an aid to differentiating between the prion proteins Prp(c) and PrP(Sc), the
      preparation and use of immobilized Proteinase K (PK) is described. An
      accumulation of PrP(Sc) in the central nervous system is the one of the causes of
      neurodegenerative disease. Current routine diagnosis is based on the postmortem
      detection of the distinct neuropathological lesion profiles of CNS and by the
      presence of the PK-resistant core of the prion protein isolated from brain
      lysates. An assay with PK immobilized to magnetic -COOH micro- and nanoparticles
      can offer a convenient as well as economic method. The individual immobilization
      steps were verified by measuring the zeta potential of the particles. The
      stability of the newly developed PK magnetic reactor, observed during kinetics
      measurements, was highly satisfactory. The calculated values of the apparent
      Michaelis constant (4.25 mM for native enzyme and 1.28 mM for immobilized enzyme)
      were determined from Lineweaver-Burk plots. Human growth hormone was digested
      using the newly prepared magnetic PK reactor and MALDI-TOF-MS analysis of the
      digests showed satisfactory efficiency. Controlled digestion of PrP(c) from the
      Mov mouse cell line was demonstrated with Western blot detection.

PMID- 18336000
TI  - Self-assembled cationic nanogels for intracellular protein delivery.
AB  - An effective intracellular protein delivery system with self-assembled cationic
      nanogels is reported. Interaction of proteins with self-assembled nanogels of
      cationic cholesteryl group-bearing pullulans (CHPNH 2) was investigated by
      dynamic light scattering (DLS), transmission electron micrograph (TEM),
      fluorescence resonance energy transfer (FRET), and fluorescence correlation
      spectroscopy (FCS). The cationic nanogels strongly interacted with bovine serum
      albumin (BSA) and formed monodispersed nanoparticels (<50 nm). The complex more
      effectively internalized into HeLa cells than cationic liposomes and a protein
      transduction domain (PTD) based carrier even in the presence of serum. The higher
      efficiency of the nanogel carrier is probably due to the formation of colloidally
      stable nanoparticles with the protein. The enzymatic activity of beta
      galactosidase (beta-Gal) was retained after internalization into cells. The
      nanogel carrier promoted nuclear delivery of a GFP-conjugated nuclear
      localization signal and Tat as a PTD (Tat-NLS-GFP). A blocking experiment with
      chemical inhibitors revealed the possible involvement of macropinocytosis in the
      uptake of the nanogel complex. After cellular uptake, the complex of the nanogel
      protein was dissociated and the protein was released inside the cell. Such a self
      assembled cationic nanogel system should create opportunities for novel
      applications of protein delivery.

PMID- 18336001
TI  - Synthesis, chaperoning, and metabolism of proteins are regulated by NT-3/TrkC
      signaling in the medulloblastoma cell line DAOY.
AB  - The human medulloblastoma cell line DAOY was transfected with Tropomyosin
      receptor kinase (TrkC), a marker for good prognostic outcome. Following TrkC
      activation by its ligand neurotrophin-3, protein extracts from DAOY cells were
      run on 2DE with subsequent MALDI-TOF-TOF analysis and quantification in order to
      detect downstream effectors. Protein levels of translational, splicing,
      processing, chaperone, protein handling, and metabolism machineries were shown to
      depend on neurotrophin-3-induced TrkC activation probably representing
      pharmacological targets.

PMID- 18336002
TI  - New insight into stimulus-induced plasticity of the olfactory epithelium in Mus
      musculus by quantitative proteomics.
AB  - The olfactory system is exposed to a plethora of chemical compounds throughout an
      organism's lifespan. Anticipation of stimuli and construction of appropriate
      neural filters present a significant challenge. This may be addressed via
      modulation of the protein composition of the sensory epithelium in response to
      environmental conditions. To reveal the mechanisms governing these changes, we
      employed a comprehensive quantitative proteomics strategy. Two groups of juvenile
      mice were treated with either pulsed or continuous application of octanal. After
      20 days of treatment, we performed a behavioral study and conducted
      electrophysiological recordings from the olfactory epithelium (OE). Both treated
      groups demonstrated peripheral desensitization to octanal; however, only the
      'continuous' group exhibited habituation. To obtain novel insight into the
      molecular mechanisms underpinning the peripheral desensitization to octanal, the
      OE proteomes of octanal-treated mice versus control were quantitatively analyzed
      using two-dimensional difference gel electrophoresis. We identified several
      significantly regulated proteins that were functionally classified as calcium
      binding proteins, cytoskeletal proteins, and lipocalins. The calcium-binding
      proteins and cytoskeletal proteins were up-regulated in the 'pulsed' group,
      whereas in the 'continuous' group, four lipocalins were significantly down
      regulated. Uniquely, the lipocalin odorant-binding protein Ia was drastically
      down-regulated in both groups. The identified proteins reflect changes throughout
      the entire OE, corresponding to changes in neuronal, non-neuronal, and
      pericellular processes. We report the regulation of several promising candidates
      for the investigation of odorant-induced changes of the OE. Among these proteins
      are different lipocalins, which seem to play a crucial role in the regulation of
      the sensitivity of the olfactory system.

PMID- 18336003
TI  - A proteomic analysis of the plasma glycoproteins of a MCF-7 mouse xenograft: a
      model system for the detection of tumor markers.
AB  - In this study, we report a plasma proteomic analysis of a mouse MCF7 xenograft,
      using a novel platform named M-LAC (multilectin affinity chromatography), in an
      attempt to identify putative serum biomarkers of tumor presence and response to
      therapy. The use of the M-LAC platform enabled us to focus on secreted proteins
      as well as remove interference from serum albumin and other nonglycosylated
      proteins. The study focused on the MCF7 human xenograft tumor model which enabled
      us to distinguish tumor proteins (human peptide sequences) from host-derived
      murine proteins, potentially discriminating tumor- versus supporting tissue
      derived markers. A large set of murine proteins was identified in this study,
      including several signaling molecules such as EGFR, interleukin-6 receptor,
      protein-kinase C, and phosphatidylinositol kinase which changed in plasma levels
      relative to tumor-free animals. We also detected in the samples with maximal
      tumor growth a number of human tumor-derived proteins linked to cell signaling,
      immune response, and transcriptional regulation. This is the first report where
      tumor-derived peptides could be detected in the serum of a xenograft model. We
      conclude that the M-LAC approach may be used to detect plasma proteins of
      potential biological significance in tumor-bearing animals and warrants further
      study in terms of increasing the sensitivity of the method for the
      characterization of low level tumor markers and to explore the applicability of
      these markers for human studies.

PMID- 18336004
TI  - A "tagless" strategy for identification of stable protein complexes genome-wide
      by multidimensional orthogonal chromatographic separation and iTRAQ reagent
      tracking.
AB  - Tandem affinity purification is the principal method for purifying and
      identifying stable protein complexes system-wide in whole cells. Although highly
      effective, this approach is laborious and impractical in organisms where genetic
      manipulation is not possible. Here, we propose a novel "tagless" strategy that
      combines multidimensional separation of endogenous complexes with mass
      spectrometric monitoring of their composition. In this procedure, putative
      protein complexes are identified based on the comigration of collections of
      polypeptides through multiple orthogonal separation steps. We present proof-of
      principle evidence for the feasibility of key aspects of this strategy. A
      majority of Escherichia coli proteins are shown to remain in stable complexes
      during fractionation of a crude extract through three chromatographic steps. We
      also demonstrate that iTRAQ reagent-based tracking can quantify relative
      migration of polypeptides through chromatographic separation media. LC MALDI MS
      and MS/MS analysis of the iTRAQ-labeled peptides gave reliable relative
      quantification of 37 components of 13 known E. coli complexes: 95% of known
      complex components closely co-eluted and 57% were automatically grouped by a
      prototype computational clustering method. With further technological
      improvements in each step, we believe this strategy will dramatically improve the
      efficiency of the purification and identification of protein complexes in cells.

PMID- 18336005
TI  - Ten-membered lactones from Phomopsis sp., an endophytic fungus of Azadirachta
      indica.
AB  - Four new 10-membered lactones ( 1- 4) and one known one ( 5) were isolated from
      the broth extract of an endophytic fungus, Phomopsis sp., obtained from the stem
      of Azadirachta indica. Their structures were assigned by analysis of
      spectroscopic data, and the structures of 1 and 4 were also confirmed by X-ray
      analysis. Compounds 1- 5 were tested for antifungal activity against several
      plant pathogens. Compound 4 demonstrated antifungal activity in the MIC value
      range 31.25-500 microg/mL.

PMID- 18336006
TI  - Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and
      monoamine oxidase inhibitory activities.
AB  - Two new xanthone glycosides, corymbiferin 3-O-beta-D-glucopyranoside (1) and
      swertiabisxanthone-I 8'-O-beta- d-glucopyranoside (2), were isolated from
      Gentianella amarella ssp. acuta, along with eight known xanthones:
      triptexanthoside C, veratriloside, corymbiferin 1-O-glucoside, swertianolin,
      norswertianolin, swertiabisxanthone-I, bellidin, and bellidifolin, four of them
      identified for the first time in G. amarella ssp. acuta. The isolation was
      conducted mainly by centrifugal partition chromatography, and the structures of
      the isolated compounds were established on the basis of spectrometric data
      including 2D NMR and mass spectrometry. Xanthones were weakly active against
      acetylcholinesterase (AChE), except triptexanthoside C, which inhibited AChE with
      an IC(50) of 13.8 +/- 1.6 microM. Some compounds were active against monoamine
      oxidases (MAO): bellidin and bellidifolin showed interesting inhibitory activity
      of MAO A, while swertianolin, the 8-O-glucopyranoside form of bellidifolin, gave
      93.6% inhibition of MAO B activity at 10(-5) M.

PMID- 18336007
TI  - Optimization of Pr3+, Tb3+, and Sm3+ co-doped (Y0.65Gd0.35)BO3:Eu0.05(3+) VUV
      phosphors through combinatorial approach.
AB  - A combinatorial approach was used to systematically investigate the effect of
      trace Pr(3+), Tb(3+), or Sm(3+) on the VUV photoluminescence of Eu(3+) in the
      Pr(3+), Tb(3+), or Sm(3+) co-doped (Y(0.65)Gd(0.35))BO(3):E(3+)(0.05). We found
      that Pr(3+) and Tb(3+)increases the VUV photoluminescent efficiency, while Sm(3+)
      decreases the efficiency. The optimized composition was identified to be between
      7 x 10(-6) and 3 x 10(-4), and the corresponding efficiency improvement is about
      15%. Scale-up experiments confirmed the results in the combinatorial materials
      libraries.

PMID- 18336008
TI  - Point defect configurations of supersaturated Au atoms inside Si nanowires.
AB  - Aberration-corrected scanning transmission electron microscopy (STEM) is used to
      reveal individual Au atom configurations inside Si nanowires grown by Au
      catalyzed vapor-liquid-solid (VLS) molecular beam epitaxy (MBE). We identify a
      substitutional and three distinct interstitial configurations, one of which has
      not been previously identified. We confirm the stability of the observed point
      defect configurations by density functional theory (DFT) calculations. The
      observed number densities of the various configurations are in accord with their
      calculated formation energies. The concentration of Au atoms is larger than the
      solubility limit, but the effect may be caused by the STEM beam.

PMID- 18336009
TI  - Microstructural investigation of magnetic CoFe2O4 nanowires inside carbon
      nanotubes by electron tomography.
AB  - Magnetic nanowires of CoFe 2O4 were casted inside the channel of multiwall carbon
      nanotubes by mild chemical synthesis. A detailed investigation of these nanowires
      was performed using mainly the electron tomography technique; this study provides
      a complete characterization of their microstructure in terms of the spatial
      organization and the size distribution of individual particles forming the
      nanowire as well as its residual porosity. In particular, we have shown that the
      size of the CoFe 2O4 monocrystalline particles is closely dependent on the
      location of the particle within the nanotube, i.e., small particles close to the
      tube tip (5 nm) and bigger particles inside the tube channel (15 nm). As the
      theoretical critical size for superparamagnetic relaxation in CoFe 2O4 is
      estimated within the range of 4-9 nm, the size distribution obtained by 3D-TEM
      agrees with the Mossbauer study that suggests the presence of two different
      magnetic components inside the nanowire. We have shown also that, by using this
      preparation method and for this internal diameter of nanotube, the CoFe 2O4
      nanowire exhibits a continuous structure along the tube, has a residual porosity
      of 38%, and can fill the tube at only 50%, parameters which influence in a
      significant manner the magnetic behavior of this system.

PMID- 18336011
TI  - Structure-function relationships in high-density docosylsilane bonded stationary
      phases by Raman spectroscopy and comparison to octadecylsilane bonded stationary
      phases: effects of common solvents.
AB  - The effects of common solvents on alkyl chain conformational order in a series of
      high-density C22 stationary phases with surface coverage ranging from 3.61 to
      6.97 micromol/m2 are investigated by Raman spectroscopy. Conformational order is
      evaluated using the intensity ratio of the antisymmetric and symmetric nu(CH2)
      modes as well as the frequencies at which these Raman bands are observed.
      Solvents studied include methanol-d4, acetonitrile-d3, water-d2, toluene-d8,
      chloroform-d. and benzene-d6. Alkyl chain conformational order and, hence,
      solvation of the stationary phase, is dependent on the Gibbs free energy change
      for these molecules at infinite dilution in hexadecane (DeltaG(o)HD), as well as
      stationary-phase properties (polymerization method and surface coverage). In
      general, polar solvents increase slightly the conformational order of these C22
      stationary phases, while nonpolar solvents decrease conformational order. A
      comparison is made between C22 and C18 bonded-phase systems to further understand
      the role of alkyl chain length on solvent-stationary phase interactions. The
      change in alkyl chain conformational order induced by solvent is also compared to
      that induced by temperature, which provides insight into the effect of
      chromatographic conditions on stationary-phase shape selectivity, an important
      application of these materials.

PMID- 18336010
TI  - Monoclonal behavior of molecularly imprinted polymer nanoparticles in capillary
      electrochromatography.
AB  - A new approach based on miniemulsion polymerization is demonstrated for synthesis
      of molecularly imprinted nanoparticles (MIP-NP; 30-150 nm) with "monoclonal"
      binding behavior. The performance of the MIP nanoparticles is characterized with
      partial filling capillary electrochromatography, for the analysis of rac
      propranolol, where (S)-propranolol is used as a template. In contrast to previous
      HPLC and CEC methods based on the use of MIPs, there is no apparent tailing for
      the enantiomer peaks, and baseline separation with 25,000-60,000 plate number is
      achieved. These effects are attributed to reduction of the MIP site heterogeneity
      by means of peripheral location of the core cross-linked NP and to MIP-binding
      sites with the same ordered radial orientation. This new MIP approach is based on
      the substitution of the functional monomers with a surfactant monomer, sodium N
      undecenoyl glycinate (SUG) for improved inclusion in the MIP-NP structure and to
      the use of a miniemulsion in the MIP-NP synthesis. The feasibility of working
      primarily with aqueous electrolytes (10 mM phosphate with a 20% acetonitrile at
      pH 7) is attributable to the micellar character of the MIP-NPs, provided by the
      inclusion of the SUG monomers in the structure. To our knowledge this is the
      first example of "monoclonal" MIP-NPs incorporated in CEC separations of drug
      enantiomers.

PMID- 18336012
TI  - Amine-capped ZnS-Mn2+ nanocrystals for fluorescence detection of trace TNT
      explosive.
AB  - Mn2+-doped ZnS nanocrystals with an amine-capping layer have been synthesized and
      used for the fluorescence detection of ultratrace 2,4,6-trinitrotoluene (TNT) by
      quenching the strong orange Mn2+ photoluminescence. The organic amine-capped
      nanocrystals can bind TNT species from solution and atmosphere by the acid-base
      pairing interaction between electron-rich amino ligands and electron-deficient
      aromatic rings. The resultant TNT anions bound onto the amino monolayer can
      efficiently quench the Mn2+ photoluminescence through the electron transfer from
      the conductive band of ZnS to the lowest unoccupied molecular orbital (LUMO) of
      TNT anions. The amino ligands provide an amplified response to the binding events
      of nitroaromatic compounds by the 2- to approximately 5-fold increase in
      quenching constants. Moreover, a large difference in quenching efficiency was
      observed for different types of nitroaromatic analytes, dependent on the affinity
      of nitro analytes to the amino monolayer and their electron-accepting abilities.
      The amine-capped nanocrystals can sensitively detect down to 1 nM TNT in solution
      or several parts-per-billion of TNT vapor in atmosphere. The ion-doped
      nanocrystal sensors reported here show a remarkable air/solution stability, high
      quantum yield, and strong analyte affinity and, therefore, are well-suited for
      detecting the ultratrace TNT and distinguishing different nitro compounds.

PMID- 18336013
TI  - Implementation and performance evaluation of a database of chemical formulas for
      the screening of pharmaco/toxicologically relevant compounds in biological
      samples using electrospray ionization-time-of-flight mass spectrometry.
AB  - Electrospray ionization (ESI)-time-of-flight (TOF) MS enables searching a wide
      number of pharmaco/toxicologically relevant compounds (PTRC) in biosamples.
      However, the number of identifiable PTRC depends on extension of reference
      database of chemical formulas/compound names. Previous approaches proposed in
      house or commercial databases with limitations either in PTRC number or content
      (e.g., few metabolites, presence of non-PTRC). In the frame of development of a
      ESI-TOF PTRC screening procedure, a subset of PubChem Compound as reference
      database is proposed. Features of this database (approximately 50,500 compounds)
      are illustrated, and its performance evaluated through analysis by capillary
      electrophoresis (CE)-ESI-TOF of hair/blood/urine collected from subjects under
      treatment with known drugs or by comparison with reference standards. The
      database is rich in parent compounds of pharmaceutical and illicit drugs,
      pesticides, and poisons and contains many metabolites (including about 6000 phase
      I metabolites and 180 glucuronides) and related substances (e.g., impurities,
      esters). The average number of hits with identical chemical formula is 1.82 +/-
      2.27 (median = 1, range 1-39). Minor deficiencies, redundancies, and errors have
      been detected that do not limit the potential of the database in identifying
      unknown PTRC. The database allows a much broader search for PTRC than other
      commercial/in-house databases of chemical formulas/compound names previously
      proposed. However, the probability that a search retrieves different PTRC having
      identical chemical formula is higher than with smaller databases, and additional
      information (anamnestic/circumstantial data, concomitant presence of parent drug
      and metabolite, selective sample preparation, liquid chromatographic retention,
      and CE migration behavior) must be used in order to focus the search more
      tightly.

PMID- 18336014
TI  - Pd(II) phthalocyanine-sensitized triplet-triplet annihilation from rubrene.
AB  - Upconverted yellow singlet fluorescence from rubrene (5,6,11,12
      tetraphenylnapthacene) was generated from selective excitation (lambdaex = 725
      nm) of the red light absorbing triplet sensitizer palladium(II)
      octabutoxyphthalocyanine, PdPc(OBu)8, in vacuum degassed toluene solutions using
      a Nd:YAG/OPO laser system in concert with gated iCCD detection. The data are
      consistent with upconversion proceeding from triplet-triplet annihilation (TTA)
      of rubrene acceptor molecules. The TTA process was confirmed by the quadratic
      dependence of the upconverted delayed fluorescence intensity with respect to
      incident light, measured by integrating the corresponding kinetic traces as a
      function of the incident excitation power. In vacuum degassed toluene solutions,
      the red-to-yellow upconversion process is stable under continuous long wavelength
      irradiation and is readily visualized by the naked eye even at modest laser
      fluence (0.6 mJ/pulse). In aerated solutions, however, selective excitation of
      the phthalocyanine sensitizer leads to rapid decomposition of rubrene into its
      corresponding endoperoxide as evidenced by UV-vis (in toluene), 1H NMR (in d6
      benzene), and MALDI-TOF mass spectrometry, consistent with the established
      reactivity of rubrene with singlet dioxygen. The upconversion process in this
      triplet sensitizer/acceptor-annihilator combination was preliminarily
      investigated in solid polymer films composed of a 50:50 mixture of an
      ethyleneoxide/epichlorohydrin copolymer, P(EO/EP). Films that were prepared under
      an argon atmosphere and maintained under this inert environment successfully
      achieve the anticipated quadratic incident power dependence, whereas air exposure
      causes the film to deviate somewhat from this dependence. To the best of our
      knowledge, the current study represents the first example of photon upconversion
      using a phthalocyanine triplet sensitizer, furthering the notion that anti-Stokes
      light-producing sensitized TTA appears to be a general phenomenon as long as
      proper energy criteria are met.

PMID- 18336015
TI  - Mechanochemical effect in the iron(III) spin crossover complex [Fe(3-MeO
      salenEt2]PF6 as studied by heat capacity calorimetry.
AB  - Magnetic and thermal properties of the iron(III) spin crossover complex [Fe(3MeO
      salenEt)(2)]PF(6) are very sensitive to mechanochemical perturbations. Heat
      capacities for unperturbed and differently perturbed samples were precisely
      determined by adiabatic calorimetry at temperatures in the 10-300 K range. The
      unperturbed compound shows a cooperative spin crossover transition at 162.31 K,
      presenting a hysteresis of 2.8 K. The anomalous enthalpy and entropy contents of
      the transition were evaluated to be Delta(trs)H = 5.94 kJ mol(-1) and Delta(trs)S
      = 36.7 J K(-1) mol(-1), respectively. By mechanochemical treatments, (1) the
      phase transition temperature was lowered by 1.14 K, (2) the enthalpy and entropy
      gains at the phase transition due to the spin crossover phenomenon were
      diminished to Delta(trs)H = 4.94 kJ mol(-1) and Delta(trs)S = 31.1 J K(-1) mol(
      1), and (3) the lattice heat capacities were larger than those of the unperturbed
      sample over the whole temperature range. In spite of different mechanical
      perturbations (grinding with a mortar and pestle and grinding in a ball-mill),
      two sets of heat capacity measurements provided basically the same results. The
      mechanochemical perturbation exerts its effect more strongly on the low-spin
      state than on the high-spin state. It shows a substantial increase of the number
      of iron(III) ions in the high-spin state below the transition temperature. The
      heat capacities of the diamagnetic cobalt(III) analogue [Co(3MeO
      salenEt)(2)]PF(6) also were measured. The lattice heat capacity of the iron
      compounds has been estimated from either the measurements on the cobalt complex
      using a corresponding states law or the effective frequency distribution method.
      These estimations have been used for the evaluation of the transition anomaly.

PMID- 18336016
TI  - Solvatochromic shift of donor-acceptor substituted bithiophene in solvents of
      different polarity: quantum chemical and molecular dynamics simulations.
AB  - The dependence of excitation energies of the solvatochromic dye, 5-dimethylamino
      5'-nitro-2,2'-bithiophene (Me(2)N-2T-NO(2)) on the solvent polarity is
      demonstrated by time-dependent density functional theory (TD-DFT) calculations in
      combination with molecular dynamics (MD) simulations. Three kinds of solvation
      models, namely, the continuum dielectric model, the discrete approach, and the
      combined discrete/continuum strategy, are employed to calculate the lowest dipole
      allowed excitation energies of Me(2)N-2T-NO(2) in seven solvents with the
      dielectric constant, epsilon, ranging from 2.23 to 111.00. Our calculations
      demonstrate the limitations of the continuum dielectric model in predicting the
      solvatochromic shift of Me(2)N-2T-NO(2) in very polar solvents with epsilon > 35.
      The accuracy of the explicit solvent model is largely limited by the size of
      supermolecular cluster. The combined discrete/continuum solvent model gives a
      satisfactory description of the bathochromic shift of Me(2)N-2T-NO(2) with
      increasing solvent polarity, in agreement with the experimental observations.

PMID- 18336017
TI  - Formation of ice-like water structure on the surface of an antifreeze protein.
AB  - Antifreeze proteins (AFPs) are found in different species from polar, alpine, and
      subarctic regions where they serve to inhibit ice crystal growth by adsorption to
      ice surfaces. Computational methods have the power to investigate the antifreeze
      mechanism in atomic detail. Molecular dynamics simulations of water under
      different conditions have been carried out to test our water model for
      simulations of biological macromolecules in extreme conditions: very low
      temperatures (200 K) and at the ice/liquid water interface. We show that the
      flexible F3C water model reproduces properties of water in the solid phase (ice
      I(h)), the supercooled liquid phase, and at the ice/liquid water interface.
      Additionally, the hydration of the type III AFP from ocean pout was studied as a
      function of temperature. Hydration waters on the ice-binding surface of the AFP
      were less distorted and more tetrahedral than elsewhere on the surface. More ice
      like hydrating water structures formed on the ice-binding surface of the protein
      such that it created an ice-like structure in water within its first hydration
      layer but not beyond, suggesting that this portion of the protein has high
      affinity for ice surfaces.

PMID- 18336018
TI  - Solvation of copper(II) sulfate in binary water/N,N-dimethylformamide mixtures:
      from the solution to the gas phase.
AB  - The solvation of copper(II) sulfate in binary mixtures of water and N,N
      dimethylformamide (DMF) is studied by a combined approach using electrochemical
      studies in solution and a mass spectrometric assay of the solvated ions formed
      from these solutions upon electrospray ionization (ESI). In the condensed phase,
      the limiting transference numbers (t(+/-)(o)) and the apparent ion association
      constants (K(A)'s) of CuSO(4) have been determined in water/DMF solutions at 20
      degrees C. The t(+)(o) values decrease with increasing DMF content, demonstrating
      a gradual solvation of Cu(2+) by DMF molecules. The association constants
      indicate that aggregation becomes more pronounced as the DMF content increases.
      In order to achieve complementary insight, the intrinsic interactions among the
      ions and solvent molecules are investigated in gas-phase experiments of the
      CuSO(4)/water/DMF system using ESI mass spectrometry. Under the conditions used,
      the dications [Cu(DMF)(n)](2+) (n = 3-6), [Cu(2)(DMF)(n)SO(4)](2+) (n = 2-7), and
      [Cu(3)(DMF)(n)(SO(4))(2)](2+) (n = 2-7), and the monocations [Cu(OH)(DMF)(n)](+),
      [Cu(DMF)(n)(HSO(4))](+) (both, n = 1-3), and [Cu(DMF)(n)](+) (n = 1, 2), are
      formed as the leading copper-containing cations. Likewise, polynuclear copper
      clusters observed in the anion ESI spectra support partial aggregation occurring
      in solution. The gas-phase studies clearly support the conclusions that (i) DMF
      is a highly preferred ligand for CuII in comparison to water and that (ii) DMF
      supports ion association for which the mass spectrometric data suggest the
      formation of polynuclear copper clusters.

PMID- 18336019
TI  - Photoelectrochemical detection of oxidative DNA damage induced by Fenton reaction
      with low concentration and DNA-associated Fe2+.
AB  - The metal ion dependent decomposition of hydrogen peroxide, the so-called Fenton
      Reaction, yields hydroxyl radicals that can cause oxidative DNA damage both in
      vitro and in vivo. We have previously reported a photoelectrochemical sensor for
      the detection of oxidative DNA damage induced by an Fe(2+)-mediated Fenton
      Reaction, using a DNA intercalator as a photoelectrochemical signal reporter
      (Liang, M.; Guo, L.-H. Environ. Sci. Technol. 2007, 41, 658). The intercalator
      binds less to the damaged DNA in the sensor film than the native form, resulting
      in a reduction in the measured photocurrent. In this report, some mechanistic
      aspects of the sensor were investigated. It was found that Fe(2+) alone (without
      the coexistence of H(2)O(2)) suppressed the photocurrent of the intercalator
      bound to the DNA film in a pH-dependent manner. Similar pH dependence was
      observed for the zeta potential of the tin oxide nanoparticle colloid used in the
      preparation of the semiconductor electrode, leading to the hypothesis that the
      metal ion binds to the surface oxide groups on the electrode and quenches the
      photoelectrochemical response. At pH 3, the quenching effect was reduced
      substantially to permit the detection of DNA damage by as low as 10 muM Fe(2+)
      and 40 microM H(2)O(2), a concentration that is within the physiologically
      relevant range. It was also found that Fe2+ ions associated with the DNA in the
      sensor film and participated in the DNA damage reaction, a mechanism that has
      been implicated in previous studies on metal carcinogenesis.

PMID- 18336020
TI  - Organic n-channel transistors based on core-cyanated perylene carboxylic diimide
      derivatives.
AB  - Five core-cyanated perylene carboxylic diimides end-functionalized with fluorine
      containing linear and cyclic substituents have been synthesized and employed in
      the fabrication of air-stable n-channel organic thin-film field-effect
      transistors with carrier mobilities up to 0.1 cm2/Vs. The relationships between
      molecular structure, thin-film morphology, substrate temperature during vacuum
      deposition, transistor performance, and air stability have been investigated. Our
      experiments led us to conclude that the role of the fluorine functionalization in
      the air-stable n-channel operation of the transistors is different than
      previously thought.

PMID- 18336021
TI  - Effective shielding of triplet energy transfer to conjugated polymer by its dense
      side chains from phosphor dopant for highly efficient electrophosphorescence.
AB  - To examine the quenching of a triplet exciton by low triplet energy (E(T))
      polymer hosts with different chain configurations for high E(T) phosphor guests,
      the quenching rate constant measurements were carried out and analyzed by the
      standard Stern-Volmer equation. We found that an effective shielding of triplet
      energy transfer from a high E(T) phosphor guest to a low E(T) polymer host is
      possible upon introducing dense side chains to the polymer to block direct
      contact from the guest such that the possibility of Dexter energy transfer
      between them is reduced to a minimum. Together with energy level matching to
      allow charge trapping on the guest, high device efficiency can be achieved. The
      extent of shielding for the systems of phenylene-based conjugated structures from
      iridium complexes follows the sequence di-substituted (octoxyl chain) in the para
      position (dC8OPPP) is greater than monosubstituted (mC8OPPP) and the PPPs with
      longer side chains are much higher than a phenylene tetramer (P4) with two short
      methyl groups. Further, capping the dialkoxyl-susbstituents with a carbazole (Cz)
      moiety (CzPPP) provides enhanced extent of shielding. Excellent device efficiency
      of 30 cd/A (8.25%) for a green electrophosphorescent device can be achieved with
      CzPPP as a host, which is higher than that of dC8OPPP as host (15 cd/A). The
      efficiency is higher than those of high E(T) conjugated polymers, poly(3,6
      carbazole) derivatives, as hosts (23 cd/A). This observation suggests a new route
      for molecular design of electroluminescent polymers as a host for a
      phosphorescent dopant.

PMID- 18336023
TI  - Solute-induced perturbations of solvent-shell molecules observed using
      multivariate Raman curve resolution.
AB  - Raman spectral features associated with the reorganization of solvent molecules
      around a solute are obtained using multivariate curve resolution. Spectra
      collected from solutions of variable concentration are resolved into unperturbed
      and perturbed components assuming only that the spectra and concentrations of
      each component are non-negative (with no peak-fitting or constraints on the
      shapes of either the perturbed or unperturbed spectral features). The
      capabilities of the method are demonstrated using solutions of acetonitrile,
      acetone, and pyridine in water as well as acetonitrile and cyclohexane in 1,2
      dichloroethane (DCE). The results reveal vibrational spectra of solvation-shell
      molecules that are perturbed by each solute. The perturbed solvent-shell water
      molecules are found to have different OH stretch bands (of higher frequency and
      narrower width than bulk water), and the gauche-trans equilibrium of solvent
      shell DCE molecules are perturbed in opposite directions by the polar and
      nonpolar solutes.

PMID- 18336024
TI  - Mechanisms of catalyst poisoning in palladium-catalyzed cyanation of haloarenes.
      remarkably facile C-N bond activation in the [(Ph3P)4Pd]/[Bu4N]+ CN- system.
AB  - Reaction paths leading to palladium catalyst deactivation during cyanation of
      haloarenes (eq 1) have been identified and studied. Each key step of the
      catalytic loop (Scheme 1) can be disrupted by excess cyanide, including ArX
      oxidative addition, X/CN exchange, and ArCN reductive elimination. The catalytic
      reaction is terminated via the facile formation of inactive [(CN)4Pd]2-,
      [(CN)3PdH]2-, and [(CN)3PdAr]2-. Moisture is particularly harmful to the
      catalysis because of facile CN- hydrolysis to HCN that is highly reactive toward
      Pd(0). Depending on conditions, the reaction of [(Ph3P)4Pd] with HCN in the
      presence of extra CN- can give rise to [(CN)4Pd]2- and/or the remarkably stable
      new hydride [(CN)3PdH]2- (NMR, X-ray). The X/CN exchange and reductive
      elimination steps are vulnerable to excess CN- because of facile phosphine
      displacement leading to stable [(CN)3PdAr]2- that can undergo ArCN reductive
      elimination only in the absence of extra CN-. When a quaternary ammonium cation
      such as [Bu4N]+ is used as a phase-transfer agent for the cyanation reaction, C-N
      bond cleavage in the cation can occur via two different processes. In the
      presence of trace water, CN- hydrolysis yields HCN that reacts with Pd(0) to give
      [(CN)3PdH]2-. This also releases highly active OH- that causes Hofmann
      elimination of [Bu4N]+ to give Bu3N, 1-butene, and water. This decomposition mode
      is therefore catalytic in H2O. Under anhydrous conditions, the formation of a new
      species, [(CN)3PdBu]2-, is observed, and experimental studies suggest that
      electron-rich mixed cyano phosphine Pd(0) species are responsible for this
      unusual reaction. A combination of experimental (kinetics, labeling) and
      computational studies demonstrate that in this case C-N activation occurs via an
      S(N)2-type displacement of amine and rule out alternative 3-center C-N oxidative
      addition or Hofmann elimination processes.

PMID- 18336025
TI  - Lithium enolates of simple ketones: structure determination using the method of
      continuous variation.
AB  - The method of continuous variation in conjunction with 6Li NMR spectroscopy was
      used to characterize lithium enolates derived from 1-indanone, cyclohexanone, and
      cyclopentanone in solution. The strategy relies on forming ensembles of homo- and
      heteroaggregated enolates. The enolates form exclusively chelated dimers in
      N,N,N',N'-tetramethylethylenediamine and cubic tetramers in tetrahydrofuran and
      1,2-dimethoxyethane.

PMID- 18336026
TI  - Identifying and alleviating electrochemical side-reactions in light-emitting
      electrochemical cells.
AB  - We demonstrate that electrochemical side-reactions involving the electrolyte can
      be a significant and undesired feature in light-emitting electrochemical cells
      (LECs). By direct optical probing of planar LECs, comprising Au electrodes and an
      active material mixture of {poly[2-methoxy-5-(2-ethylhexyloxy)-1,4
      phenylenevinylene] (MEH-PPV) + poly(ethylene oxide) (PEO) + KCF3SO3}, we show
      that two direct consequences of such a side-reaction are the appearance of a
      "degradation layer" at the negative cathode and the formation of the light
      emitting p-n junction in close proximity to the cathode. We further demonstrate
      that a high initial drive voltage and a high ionic conductivity of the active
      material strongly alleviate the extent of the side reaction, as evidenced by the
      formation of a relatively centered p-n junction, and also rationalize our
      findings in the framework of a general electrochemical model. Finally, we show
      that the doping concentrations in the doped regions at the time of the p-n
      junction formation are independent of the applied voltage and relatively balanced
      at approximately 0.11 dopants/MEH-PPV repeat unit in the p-type region and
      approximately 0.15 dopants/MEH-PPV repeat unit in the n-type region.

PMID- 18336027
TI  - An ICT-based approach to ratiometric fluorescence imaging of hydrogen peroxide
      produced in living cells.
AB  - We present the synthesis, properties, and biological applications of Peroxy
      Lucifer 1 (PL1), a new fluorescent probe for imaging hydrogen peroxide produced
      in living cells by a ratiometric response. PL1 utilizes a chemoselective boronate
      based switch to detect hydrogen peroxide by modulation of internal charge
      transfer (ICT) within a 1,8-naphthalimide dye. PL1 features high selectivity for
      hydrogen peroxide over similar reactive oxygen species, including superoxide, and
      nitric oxide, and a 65 nm shift in emission from blue-colored fluorescence to
      green-colored fluorescence upon reaction with peroxide. Two-photon confocal
      microscopy experiments in live macrophages show that PL1 can ratiometrically
      visualize localized hydrogen peroxide bursts generated in living cells at immune
      response levels.

PMID- 18336028
TI  - Mechanism of reversible alkyne coupling at zirconocene: ancillary ligand effects.
AB  - The mechanism of reversible alkyne coupling at zirconium was investigated by
      examination of the kinetics of zirconacyclopentadiene cleavage to produce free
      alkynes. The zirconacyclopentadiene rings studied possess trimethylsilyl
      substituents in the alpha-positions, and the ancillary Cp2, Me2C(eta(5)-C5H4)2,
      and CpCp* (Cp* = eta(5)-C5Me5) bis(cyclopentadienyl) ligand sets were employed.
      Fragmentation of the zirconacyclopentadiene ring in Cp2Zr[2,5-(Me3Si)2-3,4-Ph2C4]
      with PMe3, to produce Cp2Zr(eta(2)-PhC[triple bond]CSiMe3)(PMe3) and free
      PhC[triple bond]CSiMe3, is first-order in initial zirconacycle concentration and
      zero-order in incoming phosphine (k(obs) = 1.4(2) x 10(-5) s(-1) at 22 degrees
      C), and the activation parameters determined by an Eyring analysis (DeltaH(double
      dagger) = 28(2) kcal mol(-1) and DeltaS(double dagger) = 14(4) eu) are consistent
      with a dissociative mechanism. The analogous reaction of the ansa-bridged complex
      Me2C(eta(5)-C5H4)2Zr[2,5-(Me3Si)2-3,4-Ph2C4] is 100 times faster than that for
      the corresponding Cp2 complex, while the corresponding CpCp* complex reacts 20
      times slower than the Cp2 derivative. These rates appear to be largely influenced
      by the steric properties of the ancillary ligands.

PMID- 18336029
TI  - Structural versatility of anion-pi interactions in halide salts with
      pentafluorophenyl substituted cations.
AB  - A series of pentafluorophenyl substituted ammonium, iminium, amidinium, and
      phosphonium halides are presented which show extensive anion-pi interactions.
      Hereby, the well-known anion-donor-pi-acceptor as well as "eta6" anion-pi-complex
      type interactions are observed. The latter is supported by fixation of the anion
      on top of the aromatic system through hydrogen bonding. This arrangement was
      investigated by theoretical methods showing a highly attractive anion-pi
      interaction. In addition an eta2-type coordination of the anions to only two C
      atoms of the electron-deficient ring system is described.

PMID- 18336031
TI  - Oxyfunctionalization of calixarene quinone rings.
AB  - The epoxidation of quinone rings of calixquinones represents a valid route for
      the introduction of oxygenated functionalities into the de-tert-butylated
      calixarene walls originating cis-diepoxy-p-dione moieties. Carbonyl reduction of
      these systems leads to hybrid calixarenes containing dianhydroinositol moieties
      (calixinositols) belonging to the calixcyclitols family. The regio- and
      stereochemistry of these derivatives was determined by 2D NMR studies, in
      conjunction with MM3 calculations and X-ray crystallography.

PMID- 18336032
TI  - Lewis acid-catalyzed one-pot, three-component route to chiral 3,3'-bipyrroles.
AB  - 3,3'-Bipyrroles 3 could be synthesized using a double Michael addition reaction
      involving diaroyl acetylene 1 and the appropriate 1,3-dicarbonyls 2 using
      ammonium acetate as a nitrogen source. The axial chirality of bipyrrole was
      anticipated from the X-ray crystal structure and DFT calculations and confirmed
      by separating the racemates on a chiral column and subsequent CD spectra of the
      enantiomers. The absolute configuration of the enantiomers was achieved by
      theoretical CD spectra calculation using the ZINDO method.

PMID- 18336033
TI  - Visible near-infrared chemosensor for mercury ion.
AB  - A visible near-infrared chemosensor (MCy-1) for mercury ions was successfully
      devised and characterized. A large red-shift (122 nm) of the absorption maximum
      of MCy-1 was observed. An important feature for the new chemosensor is its high
      selectivity towards mercury ions over the other competitive species, making the
      "naked-eye" detection of mercury ions possible.

PMID- 18336034
TI  - Asymmetric synthesis of corsifuran A by an enantioselective oxazaborolidine
      reduction.
AB  - Corsifuran A has been prepared in an enantiomerically pure form for the first
      time by an asymmetric reduction procedure, allowing confirmation of the absolute
      stereochemistry of the natural product as (R).

PMID- 18336035
TI  - Stereospecific construction of a trans-1,4-diphosphacyclohexane skeleton.
AB  - trans-1,4-Diphosphacyclohexanes were successfully synthesized by the
      stereospecific intramolecular coupling reaction of the optically active
      bisphosphine. This is a new route for the construction of the trans-1,4
      diphosphacyclohexane skeleton. A cis isomer was also prepared along with the
      trans isomer from a mixture of rac- and meso-bisphosphines. The coordinated
      boranes were easily removed to afford the corresponding 1,4
      diphosphacyclohexanes.

PMID- 18336036
TI  - Catalytic asymmetric synthesis of allylic thiol derivatives.
AB  - The palladium(II) complex [(Rp,S)-COP-Cl]2 and its enantiomer catalyze the
      rearrangement of linear prochiral O-allyl carbamothioates under mild conditions
      to provide branched S-allyl carbamothioates in high yield and high enantiomeric
      purity.

PMID- 18336037
TI  - Epoxy-annulations by reactions of alpha-amido ketones with vinyl sulfonium salts.
      Reagent versus substrate control and kinetic resolution.
AB  - Diphenyl vinyl sulfonium salt and chiral amido-ketones undergo highly
      diastereoselective epoxy-annulation reactions in good yield. The use of a chiral
      vinyl sulfonium salt dominates the stereochemical outcome of the annulation
      reaction (reagent control is greater than substrate control), and this has
      allowed the kinetic resolution of racemic amido-ketones to be achieved.

PMID- 18336038
TI  - Diastereoselective syntheses of chroman spiroketals via [4 + 2] cycloaddition of
      enol ethers and o-quinone methides.
AB  - A variety of chroman spiroketals are synthesized via inverse-demand [4 + 2]
      cycloaddition of enol ethers and ortho-quinone methides (o-QMs). Low temperature
      o-QM generation in situ allows for the kinetic, diastereoselective construction
      of these motifs, providing entry to a number of unusual chroman spiroketal
      natural products.

PMID- 18336039
TI  - Relative rotational motion between alpha-Cyclodextrin Derivatives and a stiff
      axle molecule.
AB  - Novel [2]rotaxanes bearing alpha-cyclodextrin (alpha-CD) derivatives and a
      diphenylacetylene axis molecule with trinitrobenzene as a bulky stopper have been
      prepared to investigate the relative rotary movement of a ring relative to an
      axis molecule and that of an axis molecule in a ring by NMR techniques.
      [2]Rotaxanes 2 and 3 were composed of alpha-CD derivatives (2: 6-phenyl-amide
      alpha-CD; 3: 6-stilbene-amide-alpha-CD). The protons of alpha-CDs in rotaxanes
      were thoroughly assigned by the two-dimensional NMR techniques (TOCSY, COSY,
      ROESY, HMQC, and HMBC). The protons of alpha-CD in rotaxane 1 did not show
      splitting, whereas the resonance peak shifts and splitting for the corresponding
      protons of alpha-CD derivatives in rotaxanes 2 and 3 were observed by the
      shielding and deshielding effects from a diphenylacetylene axis molecule. The
      splitting of resonance peaks was closely related to the rotary movements of alpha
      CDs and an axis molecule. We supposed that alpha-CD in rotaxane 1 rotates freely
      around a diphenylacetylene axis molecule, and vice versa, whereas the rotary
      movement of alpha-CD derivatives and the axis molecules of rotaxanes 2 and 3 were
      restricted by the steric repulsion between the substituent group of alpha-CD and
      the stopper group of an axis molecule. To estimate the relative rotary movement
      of CDs and an axis molecule in rotaxanes, the rotational correlation time (tauc)
      of rotaxanes was measured by 13C NMR. The results indicate that the corresponding
      rotary movement of the modified alpha-CD and the axis molecules in rotaxanes 2
      and 3 depends on the size of the substituent group.

PMID- 18336040
TI  - Reactivity of fullerene epoxide: preparation of fullerene-fused thiirane,
      tetrahydrothiazolidin-2-one, and 1,3-dioxolane.
AB  - The epoxide moiety in the fullerene-mixed peroxide C60(O)(OOtBu)4 1 reacts
      readily with aryl isocyanates ArNCS (Ar = Ph, Naph) to form both the thiirane
      derivative C60(S)(OOtBu)4 and fullerene-fused tetrahydrothiazolidin-2-one. The
      reaction of 1 with trimethylsilyl isothiocyanate TMSNCS yields the isothiocyanate
      derivative C60(NCS)(OH)(OOtBu)4, the isothiocyanate and hydroxyl moieties of
      which could be converted to a fullerene-fused tetrahydrothiazolidin-2-one ring
      with alumina quantitatively. Treating 1 with BF3.Et2O yields the fullerene-fused
      [1,3,2]-dioxoborolane derivative C60(O2BOH)(OOtBu)4. In the presence of aldehyde
      or acetone, BF3.Et2O catalyzes the conversion of epoxide to fullerene-fused 1,3
      dioxolane derivatives. The products are characterized by spectroscopic data. Two
      of the compounds are also characterized by single-crystal X-ray analysis.

PMID- 18336041
TI  - "Click-fluors": modular fluorescent saccharide sensors based on a 1,2,3-triazole
      ring.
AB  - A carbohydrate sensing "click-fluor" is reported which displays a nontypical
      binding preference with sample saccharides. That a fluorescent sensor is
      generated as a result of triazole formation (click reaction), rather than simply
      bringing the sensor and reporter units together via a triazole linkage, and the
      potential applicability of the wide range of easily accessible acetylene units
      means a simple strategy for the development of modular fluorescent sensor arrays
      for rapid screening of target saccharides will be available.

PMID- 18336042
TI  - Metalated nitriles: internal 1,2-asymmetric induction.
AB  - Alkylations of conformationally constrained acyclic nitriles containing vicinal
      dimethyl groups and an adjacent phenyl group or trisubstituted alkene are
      exceptionally diastereoselective. Probing the alkylation stereoselectivity with a
      series of C- and N-metalated nitriles implicates a reactive conformation in which
      an sp2-hybridized substituent projects over the metalated nitrile to avoid
      allylic strain. Steric screening thereby directs the electrophilic attack to the
      face of the metalated nitrile opposite the projecting substituent. Excellent
      stereoselectively is maintained in a diverse range of alkylations that
      efficiently install quaternary centers, even with isopropyliodide in which a
      contiguous array of tertiary-quaternary-tertiary stereocenters is created!
      Screening the conformational requirements with a series of acyclic nitriles and
      esters reveals the key structural requirements for high selectivity while
      providing a robust, predictive model that accounts for comparable ester
      alkylations affording the opposite diastereomer! The intensive survey of
      metalated nitrile alkylations identifies the key structural features required for
      high 1,2-asymmetric induction, addresses the long-standing challenge of
      asymmetric alkylations with acylic metalated nitriles, and provides a versatile
      method for installing hindered quaternary centers with excellent stereocontrol.

PMID- 18336043
TI  - A concise synthesis of ent-Cholesterol.
AB  - ent-Cholesterol was synthesized in 16 steps from commercially available (S)
      citronellol. The overall yield for the synthesis was 2.0%. This route is amenable
      to gram-scale preparation of ent-cholesterol. Isotopic incorporation near the end
      of the synthesis was achieved using labeled methyl iodide. This synthesis is the
      most practical to date and will make ent-cholesterol more readily available to
      use as a probe of the function and metabolism of cholesterol.

PMID- 18336044
TI  - Water-soluble calix[4]resorcinarenes with hydroxyproline groups as chiral NMR
      solvating agents.
AB  - Water-soluble calix[4]resorcinarenes containing 3- and 4-hydroxyproline, d
      nipecotic acid, (S)-2-(methoxymethyl)pyrrolidine, (S)-2-pyrrolidine methanol, and
      (S,S)-(+)-2,4-bis(methoxymethyl)pyrrolidine substituents are synthesized and
      evaluated as chiral NMR solvating agents. The derivatives with the hydroxyproline
      groups are especially effective at causing enantiomeric discrimination in the
      spectra of water-soluble cationic and anionic compounds with pyridyl, phenyl, and
      bicyclic aromatic rings. Binding studies show that mono- and ortho-substituted
      phenyl rings associate within the cavity of the calix[4]resorcinarenes, as do
      naphthyl rings with mono-, 2,3-, and 1,8-substitution patterns. Anthracene
      derivatives with an amino or sulfonyl group at the 1-position bind within the
      cavity, as well. Aromatic resonances of the substrates exhibit substantial
      upfield shifts because of shielding from the aromatic rings of the
      calix[4]resorcinarene. The effectiveness of the reagents at producing chiral
      recognition in 1H NMR spectra is demonstrated with sodium mandelate, the sodium
      salt of tryptophan, and doxylamine succinate. While no one reagent is
      consistently the most effective, the calix[4]resorcinarenes with trans-4
      hydroxyproline and trans-3-hydroxyproline moieties generally produce the largest
      nonequivalence in the 1H NMR spectra of the substrates.

PMID- 18336045
TI  - Synthesis and characterization of a novel dialdehyde and cyclic anhydride.
AB  - The acid treatment of a ruthenabenzene yielded an unusual dialdehyde.
      Interestingly, this dialdehyde has notable anti-oxidative properties and resists
      even nitric acid. This stability is confirmed by chemical and electrochemical
      experiments. In addition, a stable cyclic anhydride is synthesized from the
      dialdehyde via an environmentally friendly electrochemical method.

PMID- 18336046
TI  - Predictive molecular thermodynamic models for liquid solvents, solid salts,
      polymers, and ionic liquids.

PMID- 18336047
TI  - Binding of nonsteroidal anti-inflammatory drugs to DPPC: structure and
      thermodynamic aspects.
AB  - The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the phase
      transition and phase properties of 1,2-dipalmitoylphosphatidylcholine (DPPC) has
      been investigated in both 2D (monolayers at the air/water interface) and 3D
      (multilayers in lipid/water dispersions) model systems. The 2D membrane models
      have been characterized by means of pressure-area isotherms and grazing incidence
      X-ray diffraction (GIXD) measurements. Differential scanning calorimetry (DSC)
      and simultaneous small- and wide-angle X-ray diffraction have been applied to
      lipid aqueous dispersions. All NSAIDs studied altered the main transition
      temperature of the gel to liquid-crystalline phase transition, with the
      arylacetic acid derivatives (acemetacin and indomethacin) showing the largest
      effects. A comparison of the results reveals distinct structural features of the
      membrane models after interaction with the NSAID. All drugs induced perturbations
      in the lipid liquid-crystalline phase, suggesting a major change in the hydration
      behavior of DPPC. Again, the largest effects on the structural parameters are
      found for the arylacetic acid derivatives. The results obtained in the different
      model systems give indications of the role of the membrane/NSAID interactions
      that might also be important for NSAID gastric injury.

PMID- 18336048
TI  - Lipid nanotube formation from streptavidin-membrane binding.
AB  - A novel transformation of giant lipid vesicles to produce nanotubular structures
      was observed upon the binding of streptavidin to biotinylated membranes. Unlike
      membrane budding and tubulation processes caused by proteins involved with
      endocytosis and vesicle fusion, streptavidin is known to crystallize at near the
      isoelectric point (pI 5 to 6) into planar sheets against biotinylated films. We
      have found, however, that at neutral pH membranes of low bending rigidity
      (<10kT), such as 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC),
      spontaneously produce tubular structures with widths ranging from micrometers to
      below the diffraction limit (<250 nm) and lengths spanning up to hundreds of
      micrometers. The nanotubes were typically held taut between surface-bound
      vesicles suggesting high membrane tension, yet the lipid nanotubes exhibited a
      fluidic nature that enabled the transport of entrained vesicles. Confocal
      microscopy confirmed the uniform coating of streptavidin over the vesicles and
      nanotubes. Giant vesicles composed of lipid membranes of higher bending energy
      exhibited only aggregation in the presence of streptavidin. Routes toward the
      development of these highly curved membrane structures are discussed in terms of
      general protein-membrane interactions.

PMID- 18336049
TI  - Complex pattern formation by adhesion-controlled anisotropic wrinkling.
AB  - We report complex pattern formation and shape control in the confinement-induced
      wrinkling that occurs when a poly(dimethylsiloxane) (PDMS) mold is placed on a
      bilayer of metal and polymer and then heated. Various complex structures that are
      different from the mold pattern form through the self-organization of wrinkles.
      These complex structures could be inverted in shape by manipulating the work of
      adhesion at the interface between the mold and the metal surface. Convex wrinkles
      result when the work of adhesion is relatively large. However, inverted concave
      wrinkles emerge when it is relatively small. The ratio of the mold period to the
      intrinsic wrinkling wavelength is another factor that determines the shape. The
      ability to tailor the shape of a surface is expected to have a broad range of
      applications in electro-optics and microfluidics.

PMID- 18336050
TI  - Direct imaging of aligned neurofilament networks assembled using in situ dialysis
      in microchannels.
AB  - We report a technique to produce aligned neurofilament networks for direct
      imaging and diffraction studies using in situ dialysis in a microfluidic device.
      The alignment is achieved by assembling neurofilaments from protein subunits
      confined within microchannels. Resulting network structure was probed by
      polarized optical microscopy and atomic force microscopy, which confirmed a high
      degree of protein alignment inside the microchannels. This technique can be
      expanded to facilitate structural studies of a wide range of filamentous proteins
      and their hierarchical assemblies under varying assembly conditions.

PMID- 18336052
TI  - Clinical pharmacokinetics and pharmacodynamics of desloratadine, fexofenadine and
      levocetirizine : a comparative review.
AB  - Second-generation histamine H(1) receptor antagonists were developed to provide
      efficacious treatment of allergic rhinitis (AR) and chronic idiopathic urticaria
      (CIU) while decreasing adverse effects associated with first-generation agents.
      When comparing the efficacy and safety profiles of the newest second-generation
      antihistamines - desloratadine, fexofenadine and levocetirizine - many
      pharmacological and clinical criteria must be considered. Most importantly, these
      elements should not be evaluated separately but, rather, as parts of a puzzle
      that create a whole picture. As a class, second-generation antihistamines are
      highly selective for the H(1) receptor. Some bind to it with high affinity,
      although there is marked heterogeneity among the various compounds. They have a
      limited effect on the CNS, and clinical studies have noted almost no significant
      drug-drug interactions in the agents studied. No major cytochrome P450 inhibition
      has been reported with desloratadine, fexofenadine and levocetirizine, and the
      bioavailability of desloratadine is minimally affected by drugs interfering with
      transporter molecules. Of the second-generation antihistamines, desloratadine has
      the greatest binding affinity for the H(1) receptor. The use of desloratadine,
      fexofenadine and levocetirizine is not associated with clinically relevant
      antimuscarinic effects. Desloratadine and fexofenadine do not impair cognitive or
      psychomotor functioning and are comparable with placebo in terms of somnolence.
      Based on these pharmacological characteristics, as well as clinical endpoints
      such as symptom scores, quality-of-life surveys, inflammatory cell counts and
      investigators' global evaluations, we conclude that desloratadine, fexofenadine
      and levocetirizine are all efficacious treatments for AR and CIU. However,
      differences among the antihistamines in relation to a lack of significant
      interaction with drug transporter molecules and somnolence in excess of placebo
      may provide some advantages for the overall profile of desloratadine compared
      with fexofenadine and levocetirizine.

PMID- 18336053
TI  - Facilitation of drug evaluation in children by population methods and modelling.
AB  - The pharmacokinetics and pharmacodynamics of drugs are different in adult and
      paediatric populations, the latter being particularly heterogeneous. These
      differences in pharmacokinetics and pharmacodynamics justify specific studies but
      raise a number of ethical and practical issues. The main practical difficulties
      to circumvent while performing clinical studies in children are the invasiveness
      of the procedures and the obstacles to patient recruitment. The invasiveness
      related to pain/anxiety and blood loss precludes the performance of classical
      pharmacokinetic studies in children in many instances, particularly in neonates
      and infants. Population approaches, which rely on pharmacokinetic-pharmacodynamic
      modelling, are particularly appealing in paediatric populations because these
      models can cope with sparse data. The relevance of population approaches to
      investigation of the dose-concentration-effect relationships and to
      qualitative/quantitative assessment of factors that may explain interindividual
      variability has already been emphasized. The aims of this review are to summarize
      the currently available literature on population pharmacokinetic-pharmacodynamic
      studies in children and to discuss a number of recent methodological developments
      that may facilitate the evaluation of drugs in this population by alleviating
      invasiveness and, subsequently, facilitating recruitment of patients. The present
      survey confirms that population approaches in paediatrics have already reached a
      large audience and that they are mostly used for analysis of sparse data.
      However, pharmacokinetic-pharmacodynamic studies in children are still scarce.
      New classes of models may extend the scope of the use of population models in
      paediatrics. Kinetic-pharmacodynamic models, where use of the term 'kinetic'
      rather than 'pharmacokinetic' emphasizes the absence of pharmacokinetic data, are
      indirect models where the (unobserved) drug kinetics are described by a single
      compartment involving a single rate constant. These models, which alleviate the
      need for blood samples used for the measurement of drug concentration, may be
      very useful in paediatric studies. Physiological and physiopathological models
      also have potential applications but require further development. Because the
      number of measurements in a single individual needs to be limited in children, it
      is crucial to optimize the design of the experiment in order to avoid inaccurate
      and unreliable results. In this review, formal optimization and simulation to
      evaluate a design are presented, and specific problems raised by the application
      of these techniques in paediatrics are addressed. Finally, the related technique
      of clinical trial simulation and its applications are presented and discussed.

PMID- 18336054
TI  - Identification of intestinal loss of a drug through physiologically based
      pharmacokinetic simulation of plasma concentration-time profiles.
AB  - BACKGROUND AND OBJECTIVE: Despite recent advances in understanding of the role of
      the gut as a metabolizing organ, recognition of gut wall metabolism and/or other
      factors contributing to intestinal loss of a compound has been a challenging task
      due to the lack of well characterized methods to distinguish it from first-pass
      hepatic extraction. The implications of identifying intestinal loss of a compound
      in drug discovery and development can be enormous. Physiologically based
      pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple,
      reliable and cost-effective way to understand the mechanisms underlying
      pharmacokinetic processes. The purpose of this article is to demonstrate the
      application of PBPK simulations in bringing to light intestinal loss of orally
      administered drugs, using two example compounds: verapamil and an in-house
      compound that is no longer in development (referred to as compound A in this
      article). METHODS: A generic PBPK model, built in-house using MATLAB software and
      incorporating absorption, metabolism, distribution, biliary and renal elimination
      models, was employed for simulation of concentration-time profiles. Modulation of
      intrinsic hepatic clearance and tissue distribution parameters in the generic
      PBPK model was done to achieve a good fit to the observed intravenous
      pharmacokinetic profiles of the compounds studied. These optimized clearance and
      distribution parameters are expected to be invariant across different routes of
      administration, as long as the kinetics are linear, and were therefore employed
      to simulate the oral profiles of the compounds. For compounds with reasonably
      good solubility and permeability, an area under the concentration-time curve for
      the simulated oral profile that far exceeded the observed would indicate some
      kind of loss in the intestine. RESULTS: PBPK simulations applied to compound A
      showed substantial loss of the compound in the gastrointestinal tract in humans
      but not in rats. This accounted for the lower bioavailability of the compound in
      humans than in rats. PBPK simulations of verapamil identified gut wall
      metabolism, well established in the literature, and showed large interspecies
      differences with respect to both gut wall metabolism and drug-induced delays in
      gastric emptying. CONCLUSIONS: Mechanistic insights provided by PBPK simulations
      can be very valuable in answering vital questions in drug discovery and
      development. However, such applications of PBPK models are limited by the lack of
      accurate inputs for clearance and distribution. This article demonstrates a
      successful application of PBPK simulations to identify and quantify intestinal
      loss of two model compounds in rats and humans. The limitation of inaccurate
      inputs for the clearance and distribution parameters was overcome by optimizing
      these parameters through fitting intravenous profiles. The study also
      demonstrated that the large interspecies differences associated with gut wall
      metabolism and gastric emptying, evident for the compounds studied, make animal
      model extrapolations to humans unreliable. It is therefore important to do PBPK
      simulations of human pharmacokinetic profiles to understand the relevance of
      intestinal loss of a compound in humans.

PMID- 18336055
TI  - Evaluation of a generic physiologically based pharmacokinetic model for lineshape
      analysis.
AB  - BACKGROUND AND OBJECTIVE: The mechanistic framework of physiologically based
      pharmacokinetic (PBPK) models makes them uniquely suited to hypothesis testing
      and lineshape analysis, which help provide valuable insights into mechanisms that
      contribute to the observed concentration-time profiles. The aim of this article
      is to evaluate the utility of PBPK models for simulating oral lineshapes by
      optimizing clearance and distribution parameters through fitting observed
      intravenous pharmacokinetic profiles. METHODS: A generic PBPK model, built in
      house using MATLAB software and incorporating absorption, metabolism,
      distribution, biliary and renal elimination models, was employed for simulation
      of the concentration-time profiles of nine marketed drugs with diverse
      physicochemical and pharmacokinetic profiles and absorption rates determined
      solely by transcellular or paracellular permeability and solubility. The model is
      based on easily available physicochemical properties of compounds such as the log
      P, acid dissociation constant and solubility, and in vitro pharmacokinetic data
      such as Caco-2 permeability, the fraction of the compound unbound in plasma, and
      microsomal or hepatocyte intrinsic clearance. Clearance and distribution
      parameters optimized through simulation of intravenous profiles were used to
      simulate their corresponding oral profiles, which are determined by a multitude
      of parameters, both compound-dependent and physiological. Comparison of the
      simulated and observed oral profiles was done using goodness-of-fit parameters
      such as the reduced chi(2) statistic. Fold errors were calculated for the area
      under the plasma concentration-time curve (AUC), maximum plasma concentration
      (C(max)) and time to reach the C(max) (t(max)), to assess the accuracy of
      predictions. RESULTS: The approach of predicting the oral profiles by optimizing
      the clearance and distribution parameters using the observed intravenous profile
      seemed to perform well for the nine compounds chosen for the study. The mean fold
      error for oral pharmacokinetic parameters, such as the C(max), t(max) and AUC,
      and for lineshape simulation was within 2-fold. CONCLUSIONS: The validation of
      the generic PBPK model built in-house demonstrated that as long as the absorption
      profile of a compound is determined solely by solubility and paracellular or
      transcellular permeability, the PBPK simulations of oral profiles using optimized
      parameters from intravenous simulations provide reasonably good agreement with
      the observed profile with respect to both the lineshape fit and prediction of
      pharmacokinetic parameters. Therefore, any lineshape mismatch between PBPK
      simulated and observed oral profiles can be interpreted suitably to gain
      mechanistic insights into the pharmacokinetic processes that have resulted in the
      observed lineshape. A strategy has been proposed to identify involvement of
      carrier-mediated transport; clearance saturation; enterohepatic recirculation of
      the parent compound; extra-hepatic, extra-gut elimination; higher in vivo
      solubility than predicted in vitro; drug-induced gastric emptying delays; gut
      loss and regional variation in gut absorption.

PMID- 18336056
TI  - Pharmacokinetic study of mycophenolate mofetil in patients with systemic lupus
      erythematosus and design of Bayesian estimator using limited sampling strategies.
AB  - BACKGROUND: Monitoring of the area under the plasma concentration-time curve
      (AUC) of mycophenolic acid (MPA) has been developed for individual dose
      adjustment of mycophenolate mofetil (MMF) in renal allograft recipients. MMF is
      currently used as an off-label drug in the treatment of systemic lupus
      erythematosus (SLE), but factors of its exposition may be different in these
      patients and need to be determined for therapeutic drug monitoring (TDM)
      purposes. OBJECTIVE: The aim of the study was to develop a maximum a posteriori
      probability (MAP) Bayesian estimator of MPA exposition in patients with SLE, with
      the objective of TDM based on a limited sample strategy. METHODS: Twenty adult
      patients with SLE given a stable 1 g/day, 2 g/day or 3 g/day dose of MMF orally
      for at least 10 weeks were included in the study. MPA was measured by high
      performance liquid chromatography (HPLC) coupled to a photodiode array detector
      (11 plasma measurements over 12 hours post-dose per patient). Free MPA
      concentrations were measured by HPLC with fluorescence detection. Two different
      one-compartment models with first-order elimination were tested to fit the data:
      one convoluted with a double gamma distribution to describe secondary
      concentrations peaks, and one convoluted with a triple gamma distribution to
      model a third, later peak. RESULTS: A large interindividual variability in MPA
      concentration-time profiles was observed. The mean maximum plasma concentration,
      trough plasma concentration, time to reach the maximum plasma concentration and
      AUC from 0 to 12 hours (AUC(12)) were 13.6 +/- 8.4 microg/mL, 1.4 +/- 1.2
      microg/mL, 1.1 +/- 1.2 hours and 32.2 +/- 17.1microg . h/mL, respectively. The
      mean free fraction of MPA was 1.7%. The one-compartment model with first-order
      elimination convoluted with a triple gamma distribution best fitted the data.
      Accurate Bayesian estimates of the AUC(12) were obtained using three blood
      samples collected at 40 minutes, 2 hours and 3 hours, with a coefficient of
      correlation (R) = 0.95 between the observed and predicted AUC(12) and with a
      difference of <20% in 16 of the 20 patients. CONCLUSION: A specific
      pharmacokinetic model was built to accurately fit MPA blood concentration-time
      profiles after MMF oral dosing in SLE patients, which allowed development of an
      accurate Bayesian estimator of MPA exposure that should allow MMF monitoring
      based on the AUC(12) in these patients. The predictive value of targeting one
      specific or different AUC values on patients' outcome using this estimator in SLE
      will need to be evaluated.

PMID- 18336057
TI  - Use of smoking cessation therapies in individuals with psychiatric illness : an
      update for prescribers.
AB  - Individuals with mental illness are particularly disadvantaged by their use of
      tobacco, spending as much as 40% of their income on cigarettes. They also have
      increased mortality from cardiovascular and respiratory disorders. The most
      effective interventions to help psychiatric patients stop smoking are similar to
      those that are effective in the general population. These include psychological
      treatments, nicotine replacement therapy (NRT), bupropion and nortriptyline, at
      least in the short term. Most studies agree that these gains can be achieved in
      the absence of significant adverse effects in terms of psychological morbidity.
      Effects diminish over time, but these findings also apply to the general
      population. The best long-term results have come from extended prescription and
      psychological interventions, and apply equally to patients with and without a
      history of psychiatric disorder, such as major depression. In spite of this,
      clinicians are not fully exploiting opportunities to help psychiatric patients
      stop smoking. It is not possible to plan a programme to help individuals stop
      smoking in mental health settings unless factors such as demographics, diagnosis
      and concurrent medication are taken into account.

PMID- 18336058
TI  - Assessing the efficacy of treatments for ADHD : overview of methodological
      issues.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common and impairing
      psychiatric condition that affects significant numbers of children, adolescents
      and adults. Clinicians in a variety of practice settings (hospital, outpatient,
      residential, research) strive to diagnose, treat and monitor ADHD in an efficient
      and evidence-based manner. Tools that facilitate the gathering and interpretation
      of information from a variety of sources can effectively augment a diagnostic
      assessment, and can also be useful for longitudinal monitoring. Multiple
      assessment tools are available, with varying degrees of psychometric validity,
      clinical utility and overall feasibility (time and cost). This review provides an
      overview of several available ADHD rating scales and continuous performance
      tests, and offers a discussion of potential strengths and weaknesses of the
      instruments. While these tools do not in and of themselves make a diagnosis of
      ADHD, they can certainly assist in the diagnostic assessment, be crucial in
      assessing the efficacy of medications in clinical trials, and be a useful adjunct
      in the clinical management of ADHD.

PMID- 18336060
TI  - Pregnancy outcome after in utero exposure to valproate : evidence of dose
      relationship in teratogenic effect.
AB  - BACKGROUND: Valproate is a first-line antiepileptic agent and is also used in the
      treatment of bipolar disorder and migraine. It is a known human teratogen. The
      objective of the study was to evaluate the teratogenic risk of valproate.
      METHODS: All callers who contacted the Israeli Teratology Information Service
      (TIS) between 1994 and 2004 for information about gestational exposure to
      valproate were enrolled in the study. After the expected date of delivery, these
      women were followed up by telephone interview about their pregnancy outcome using
      a structured questionnaire. Data obtained from women who contacted the TIS about
      valproate exposure during pregnancy were then compared with data obtained from
      callers who were counselled for nonteratogenic exposures over the same timeframe.
      The main outcome measure was the rate of major congenital anomalies. RESULTS: The
      outcomes of 154 valproate-exposed pregnancies (96.1% at least in the first
      trimester) were compared with those of 1315 pregnancies of women in the TIS
      database who were counselled for nonteratogenic exposures. The rate of major
      anomalies (some multiple) in the valproate group exposed in the first trimester
      was higher compared with controls after exclusion of genetic or cytogenetic
      anomalies (8 of 120 [6.7%] vs 31 of 1236 [2.5%], p = 0.018, relative risk [RR] =
      2.66, 95% CI 1.25, 5.65). There were no cases of neural tube defect in the
      valproate-exposed group. Five of the eight major anomalies in the valproate group
      were cardiovascular, two of eight were mentally retarded, two of five male
      infants with major anomalies had hypospadias and three of eight were suspected of
      having fetal valproate syndrome. A daily dose > or =1000 mg was associated with
      the highest teratogenic risk (7 of 32 [21.9%] vs 31 of 1236 [2.5%], RR = 8.72,
      95% CI 4.16, 18.30). In the subgroup exposed to polytherapy there was a 4-fold
      increase in the rate of major anomalies compared with controls. All major
      anomalies were in the group treated for epilepsy. CONCLUSION: When valproate
      treatment cannot be avoided in the first trimester of pregnancy, the lowest
      effective dose should be prescribed, preferably as monotherapy, to minimize its
      teratogenic risk.

PMID- 18336061
TI  - Intramuscular aripiprazole : a review of its use in the management of agitation
      in schizophrenia and bipolar I disorder.
AB  - An intramuscular formulation of the atypical antipsychotic aripiprazole (Abilify)
      has been developed and is approved in the EU for use in agitation and disturbed
      behaviour associated with schizophrenia. In the US, it is approved for the
      treatment of agitation associated with schizophrenia or bipolar I disorder (manic
      or mixed). In large, well designed trials, intramuscular aripiprazole was an
      effective and generally well tolerated treatment for agitation associated with
      schizophrenia, schizoaffective disorder, schizophreniform disorder or bipolar I
      disorder. Intramuscular aripiprazole was more effective than placebo in these
      patient populations and was noninferior to intramuscular haloperidol in those
      with agitation associated with schizophrenia and its related disorders.
      Aripiprazole is associated with a low risk for extrapyramidal symptoms (EPS),
      cardiac effects, hyperprolactinaemia, weight gain and other metabolic
      disturbances. Head-to-head trials comparing intramuscular aripiprazole with other
      intramuscular atypical antipsychotics are required before the relative position
      of each of these agents can be fully determined. In the meantime, intramuscular
      aripiprazole, with its favourable tolerability profile, is a valuable treatment
      option for agitation in patients with schizophrenia, schizoaffective disorder,
      schizophreniform disorder or bipolar I disorder.

PMID- 18336059
TI  - Current management of pain associated with multiple sclerosis.
AB  - While pain is a common problem in patients with multiple sclerosis (MS), it is
      not frequently mentioned by patients and a more direct approach is required in
      order to obtain information about pain from patients. Many patients with MS
      experience more than one pain syndrome; combinations of dysaesthesia, headaches
      and/or back or muscle and joint pain are frequent. For each pain syndrome a clear
      diagnosis and therapeutic concept needs to be established. Pain in MS can be
      classified into four diagnostically and therapeutically relevant categories: (i)
      neuropathic pain due to MS (pain directly related to MS); (ii) pain indirectly
      related to MS; (iii) MS treatment-related pain; and (iv) pain unrelated to MS.
      Painful paroxysmal symptoms such as trigeminal neuralgia (TN), or painful tonic
      spasms are treated with antiepileptics as first choice, e.g. carbamazepine,
      oxcarbazepine, lamotrigine, gabapentin, pregabalin, etc. Painful 'burning'
      dysaesthesias, the most frequent chronic pain syndrome, are treated with TCAs
      such as amitriptyline, or antiepileptics such as gabapentin, pregabalin,
      lamotrigine, etc. Combinations of drugs with different modes of action can be
      particularly useful for reducing adverse effects. While escalation therapy may
      require opioids, there are encouraging results from studies regarding
      cannabinoids, but their future role in the treatment of MS-related pain has still
      to be determined. Pain related to spasticity often improves with adequate
      physiotherapy. Drug treatment includes antispastic agents such as baclofen or
      tizanidine and in patients with phasic spasticity, gabapentin or levetiracetam
      are administered. In patients with severe spasticity, botulinum toxin injections
      or intrathecal baclofen merit consideration. While physiotherapy may ameliorate
      malposition-induced joint and muscle pain, additional drug treatment with
      paracetamol (acetaminophen) or NSAIDs may be useful. Moreover, painful pressure
      lesions should be avoided by using optimally adjusted aids. Treatment-related
      pain associated with MS can occur with subcutaneous injections of interferon-beta
      or glatiramer acetate, and may be reduced by optimizing the injection technique
      and by local cooling. Systemic (particularly 'flu-like') adverse effects of
      interferons, e.g. myalgias, can be reduced by administering paracetamol,
      ibuprofen or naproxen. A potential increase in the frequency of pre-existing
      headaches after starting treatment with interferons may require optimization of
      headache attack therapy or even prophylactic treatment. Pain unrelated to MS,
      such as back pain or headache, is common in patients with MS and may deteriorate
      as a result of the disease. In summary, a careful analysis of each pain syndrome
      will allow the design of the appropriate treatment plan using various medical and
      nonmedical options (multimodal therapy), and will thus help to improve the
      quality of life (QOL) of the patients.

PMID- 18336062
TI  - Exploring the developmental overnutrition hypothesis using parental-offspring
      associations and FTO as an instrumental variable.
AB  - BACKGROUND: The developmental overnutrition hypothesis suggests that greater
      maternal obesity during pregnancy results in increased offspring adiposity in
      later life. If true, this would result in the obesity epidemic progressing across
      generations irrespective of environmental or genetic changes. It is therefore
      important to robustly test this hypothesis. METHODS AND FINDINGS: We explored
      this hypothesis by comparing the associations of maternal and paternal pre
      pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry
      (DXA)-determined fat mass measured at 9 to 11 y (4,091 parent-offspring trios)
      and by using maternal FTO genotype, controlling for offspring FTO genotype, as an
      instrument for maternal adiposity. Both maternal and paternal BMI were positively
      associated with offspring fat mass, but the maternal association effect size was
      larger than that in the paternal association in all models: mean difference in
      offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI
      0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13
      (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001.
      The stronger maternal association was robust to sensitivity analyses assuming
      levels of non-paternity up to 20%. When maternal FTO, controlling for offspring
      FTO, was used as an instrument for the effect of maternal adiposity, the mean
      difference in offspring fat mass z-score per 1 standard deviation maternal BMI
      was -0.08 (95% CI: -0.56 to 0.41), with no strong statistical evidence that this
      differed from the observational ordinary least squares analyses (p = 0.17).
      CONCLUSIONS: Neither our parental comparisons nor the use of FTO genotype as an
      instrumental variable, suggest that greater maternal BMI during offspring
      development has a marked effect on offspring fat mass at age 9-11 y.
      Developmental overnutrition related to greater maternal BMI is unlikely to have
      driven the recent obesity epidemic.

PMID- 18336063
TI  - Global transcript profiles of fat in monozygotic twins discordant for BMI:
      pathways behind acquired obesity.
AB  - BACKGROUND: The acquired component of complex traits is difficult to dissect in
      humans. Obesity represents such a trait, in which the metabolic and molecular
      consequences emerge from complex interactions of genes and environment. With the
      substantial morbidity associated with obesity, a deeper understanding of the
      concurrent metabolic changes is of considerable importance. The goal of this
      study was to investigate this important acquired component and expose obesity
      induced changes in biological pathways in an identical genetic background.
      METHODS AND FINDINGS: We used a special study design of "clonal controls," rare
      monozygotic twins discordant for obesity identified through a national registry
      of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male,
      six female; white), with a mean +/- standard deviation (SD) age 25.8 +/- 1.4 y
      and a body mass index (BMI) difference 5.2 +/- 1.8 kg/m(2). Sequence analyses of
      mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed
      no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was
      reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of
      the adipose tissue transcription profiles exposed significant down-regulation of
      mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line
      with this finding, serum levels of insulin secretion-enhancing BCAAs were
      increased in obese male co-twins (9% increase, p = 0.025). Lending clinical
      relevance to the findings, in both sexes the observed aberrations in
      mitochondrial amino acid metabolism pathways in fat correlated closely with liver
      fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of
      acquired obesity in these healthy young adults. CONCLUSIONS: Our findings
      emphasize a substantial role of mitochondrial energy- and amino acid metabolism
      in obesity and development of insulin resistance.

PMID- 18336064
TI  - The impact of monitoring HIV patients prior to treatment in resource-poor
      settings: insights from mathematical modelling.
AB  - BACKGROUND: The roll-out of antiretroviral treatment (ART) in developing
      countries concentrates on finding patients currently in need, but over time many
      HIV-infected individuals will be identified who will require treatment in the
      future. We investigated the potential influence of alternative patient management
      and ART initiation strategies on the impact of ART programmes in sub-Saharan
      Africa. METHODS AND FINDINGS: We developed a stochastic mathematical model
      representing disease progression, diagnosis, clinical monitoring, and survival in
      a cohort of 1,000 hypothetical HIV-infected individuals in Africa. If individuals
      primarily enter ART programmes when symptomatic, the model predicts that only 25%
      will start treatment and, on average, 6 life-years will be saved per person
      treated. If individuals are recruited to programmes while still healthy and are
      frequently monitored, and CD4(+) cell counts are used to help decide when to
      initiate ART, three times as many are expected to be treated, and average life
      years saved among those treated increases to 15. The impact of programmes can be
      improved further by performing a second CD4(+) cell count when the initial value
      is close to the threshold for starting treatment, maintaining high patient follow
      up rates, and prioritising monitoring the oldest (> or = 35 y) and most immune
      suppressed patients (CD4(+) cell count < or = 350). Initiating ART at higher
      CD4(+) cell counts than WHO recommends leads to more life-years saved, but
      disproportionately more years spent on ART. CONCLUSIONS: The overall impact of
      ART programmes will be limited if rates of diagnosis are low and individuals
      enter care too late. Frequently monitoring individuals at all stages of HIV
      infection and using CD4 cell count information to determine when to start
      treatment can maximise the impact of ART.

PMID- 18336065
TI  - Further evidence that exclusive breast-feeding reduces mother-to-child HIV
      transmission compared with mixed feeding.

PMID- 18336066
TI  - Determining origins and causes of childhood obesity via Mendelian randomization
      analysis.

PMID- 18336067
TI  - Observational research, randomised trials, and two views of medical science.

PMID- 18336068
TI  - Creatine kinase-mediated ATP supply fuels actin-based events in phagocytosis.
AB  - Phagocytosis requires locally coordinated cytoskeletal rearrangements driven by
      actin polymerization and myosin motor activity. How this actomyosin dynamics is
      dependent upon systems that provide access to ATP at phagosome microdomains has
      not been determined. We analyzed the role of brain-type creatine kinase (CK-B),
      an enzyme involved in high-energy phosphoryl transfer. We demonstrate that
      endogenous CK-B in macrophages is mobilized from the cytosolic pool and
      coaccumulates with F-actin at nascent phagosomes. Live cell imaging with XFP
      tagged CK-B and beta-actin revealed the transient and specific nature of this
      partitioning process. Overexpression of a catalytic dead CK-B or CK-specific
      cyclocreatine inhibition caused a significant reduction of actin accumulation in
      the phagocytic cup area, and reduced complement receptor-mediated, but not Fc
      gammaR-mediated, ingestion capacity of macrophages. Finally, we found that
      inhibition of CK-B affected phagocytosis already at the stage of particle
      adhesion, most likely via effects on actin polymerization behavior. We propose
      that CK-B activity in macrophages contributes to complement-induced F-actin
      assembly events in early phagocytosis by providing local ATP supply.

PMID- 18336069
TI  - A putative cation channel, NCA-1, and a novel protein, UNC-80, transmit neuronal
      activity in C. elegans.
AB  - Voltage-gated cation channels regulate neuronal excitability through selective
      ion flux. NALCN, a member of a protein family that is structurally related to the
      alpha1 subunits of voltage-gated sodium/calcium channels, was recently shown to
      regulate the resting membrane potentials by mediating sodium leak and the firing
      of mouse neurons. We identified a role for the Caenorhabditis elegans NALCN
      homologues NCA-1 and NCA-2 in the propagation of neuronal activity from cell
      bodies to synapses. Loss of NCA activities leads to reduced synaptic transmission
      at neuromuscular junctions and frequent halting in locomotion. In vivo calcium
      imaging experiments further indicate that while calcium influx in the cell bodies
      of egg-laying motorneurons is unaffected by altered NCA activity, synaptic
      calcium transients are significantly reduced in nca loss-of-function mutants and
      increased in nca gain-of-function mutants. NCA-1 localizes along axons and is
      enriched at nonsynaptic regions. Its localization and function depend on UNC-79,
      and UNC-80, a novel conserved protein that is also enriched at nonsynaptic
      regions. We propose that NCA-1 and UNC-80 regulate neuronal activity at least in
      part by transmitting depolarization signals to synapses in C. elegans neurons.

PMID- 18336070
TI  - Boosting virology in Brazil.

PMID- 18336071
TI  - Postmitotic specification of Drosophila insulinergic neurons from pioneer
      neurons.
AB  - Insulin and related peptides play important and conserved functions in growth and
      metabolism. Although Drosophila has proved useful for the genetic analysis of
      insulin functions, little is known about the transcription factors and cell
      lineages involved in insulin production. Within the embryonic central nervous
      system, the MP2 neuroblast divides once to generate a dMP2 neuron that initially
      functions as a pioneer, guiding the axons of other later-born embryonic neurons.
      Later during development, dMP2 neurons in anterior segments undergo apoptosis but
      their posterior counterparts persist. We show here that surviving posterior dMP2
      neurons no longer function in axonal scaffolding but differentiate into
      neuroendocrine cells that express insulin-like peptide 7 (Ilp7) and innervate the
      hindgut. We find that the postmitotic transition from pioneer to insulin
      producing neuron is a multistep process requiring retrograde bone morphogenetic
      protein (BMP) signalling and four transcription factors: Abdominal-B, Hb9, Fork
      Head, and Dimmed. These five inputs contribute in a partially overlapping manner
      to combinatorial codes for dMP2 apoptosis, survival, and insulinergic
      differentiation. Ectopic reconstitution of this code is sufficient to activate
      Ilp7 expression in other postmitotic neurons. These studies reveal striking
      similarities between the transcription factors regulating insulin expression in
      insect neurons and mammalian pancreatic beta-cells.

PMID- 18336072
TI  - A role for parasites in stabilising the fig-pollinator mutualism.
AB  - Mutualisms are interspecific interactions in which both players benefit.
      Explaining their maintenance is problematic, because cheaters should outcompete
      cooperative conspecifics, leading to mutualism instability. Monoecious figs
      (Ficus) are pollinated by host-specific wasps (Agaonidae), whose larvae gall
      ovules in their "fruits" (syconia). Female pollinating wasps oviposit directly
      into Ficus ovules from inside the receptive syconium. Across Ficus species, there
      is a widely documented segregation of pollinator galls in inner ovules and seeds
      in outer ovules. This pattern suggests that wasps avoid, or are prevented from
      ovipositing into, outer ovules, and this results in mutualism stability. However,
      the mechanisms preventing wasps from exploiting outer ovules remain unknown. We
      report that in Ficus rubiginosa, offspring in outer ovules are vulnerable to
      attack by parasitic wasps that oviposit from outside the syconium. Parasitism
      risk decreases towards the centre of the syconium, where inner ovules provide
      enemy-free space for pollinator offspring. We suggest that the resulting gradient
      in offspring viability is likely to contribute to selection on pollinators to
      avoid outer ovules, and by forcing wasps to focus on a subset of ovules, reduces
      their galling rates. This previously unidentified mechanism may therefore
      contribute to mutualism persistence independent of additional factors that invoke
      plant defences against pollinator oviposition, or physiological constraints on
      pollinators that prevent oviposition in all available ovules.

PMID- 18336073
TI  - Phenotypic mismatches reveal escape from arms-race coevolution.
AB  - Because coevolution takes place across a broad scale of time and space, it is
      virtually impossible to understand its dynamics and trajectories by studying a
      single pair of interacting populations at one time. Comparing populations across
      a range of an interaction, especially for long-lived species, can provide insight
      into these features of coevolution by sampling across a diverse set of conditions
      and histories. We used measures of prey traits (tetrodotoxin toxicity in newts)
      and predator traits (tetrodotoxin resistance of snakes) to assess the degree of
      phenotypic mismatch across the range of their coevolutionary interaction.
      Geographic patterns of phenotypic exaggeration were similar in prey and
      predators, with most phenotypically elevated localities occurring along the
      central Oregon coast and central California. Contrary to expectations, however,
      these areas of elevated traits did not coincide with the most intense
      coevolutionary selection. Measures of functional trait mismatch revealed that
      over one-third of sampled localities were so mismatched that reciprocal selection
      could not occur given current trait distributions. Estimates of current locality
      specific interaction selection gradients confirmed this interpretation. In every
      case of mismatch, predators were "ahead" of prey in the arms race; the converse
      escape of prey was never observed. The emergent pattern suggests a dynamic in
      which interacting species experience reciprocal selection that drives arms-race
      escalation of both prey and predator phenotypes at a subset of localities across
      the interaction. This coadaptation proceeds until the evolution of extreme
      phenotypes by predators, through genes of large effect, allows snakes to, at
      least temporarily, escape the arms race.

PMID- 18336074
TI  - Laparoscopy-assisted ureter interposition by ileum.
AB  - PURPOSE: To report our experience with the laparoscopic approach to managing
      ileal ureter substitution for extensive ureteral stenosis. PATIENTS AND METHODS:
      Two patients, one man and one woman, ages 38 and 51 years, respectively,
      underwent laparoscopic ileal substitution between March 2004 and December 2005
      because of extensive ureteral stenosis after stone disease management. A three
      port technique was used. The ileal segment was managed extracorporeally through a
      McBurney incision. Pyeloileal or ileoureteral anastomosis was performed
      intracorporeally. Follow-up included clinical evaluation, nuclear renography,
      intravenous urography. and serum chemistry analysis. RESULTS: There were no
      complications, and there was minimal blood loss. Mean operative time was 195
      minutes (range 180-210 min). Both patients remain without any symptoms or
      complaints at a median of 18.5 months follow-up (range 8-29 months).
      Postoperative pyelography verified adequate excretion from the renal unit.
      Nuclear renography showed no evidence of loss of renal function. No evident
      variations of preoperative and postoperative serum chemistry values were noted.
      None of the patients had any complaint or symptoms of urinary-tract infection or
      urolithiasis. CONCLUSIONS: The laparoscopic approach appears to be a safe and
      effective alternative to open surgery for ileal ureter substitution.
      Extracorporeal management of the ileal segment would appear advantageous because
      it reduces operative time and morbidity.

PMID- 18336075
TI  - 3D Axon structure extraction and analysis in confocal fluorescence microscopy
      images.
AB  - The morphological properties of axons, such as their branching patterns and
      oriented structures, are of great interest for biologists in the study of the
      synaptic connectivity of neurons. In these studies, researchers use triple
      immunofluorescent confocal microscopy to record morphological changes of neuronal
      processes. Three-dimensional (3D) microscopy image analysis is then required to
      extract morphological features of the neuronal structures. In this article, we
      propose a highly automated 3D centerline extraction tool to assist in this task.
      For this project, the most difficult part is that some axons are overlapping such
      that the boundaries distinguishing them are barely visible. Our approach combines
      a 3D dynamic programming (DP) technique and marker-controlled watershed algorithm
      to solve this problem. The approach consists of tracking and updating along the
      navigation directions of multiple axons simultaneously. The experimental results
      show that the proposed method can rapidly and accurately extract multiple axon
      centerlines and can handle complicated axon structures such as cross-over
      sections and overlapping objects.

PMID- 18336076
TI  - Sensitivity derivatives for flexible sensorimotor learning.
AB  - To learn effectively, an adaptive controller needs to know its sensitivity
      derivatives--the variables that quantify how system performance depends on the
      commands from the controller. In the case of biological sensorimotor control, no
      one has explained how those derivatives themselves might be learned, and some
      authors suggest they are not learned at all but are known innately. Here we show
      that this knowledge cannot be solely innate, given the adaptive flexibility of
      neural systems. And we show how it could be learned using forms of information
      transport that are available in the brain. The mechanism, which we call implicit
      supervision, helps explain the flexibility and speed of sensorimotor learning and
      our ability to cope with high-dimensional work spaces and tools.

PMID- 18336077
TI  - Can spike coordination be differentiated from rate covariation?
AB  - There has been a long and lively debate on whether rate covariance and temporal
      coordination of spikes, regarded as potential origins for correlations in
      cortical spike signals, fulfill different roles in the cortical code. In this
      context, studies that report spike coordination have often been criticized for
      ignoring fast nonstationarities, which would result in wrongly assigned spike
      coordination. The underlying hypothesis of this critique is that spike
      coordination is essentially identical to rate covariation, only on a shorter
      timescale. This study investigates the validity of this critique. We provide a
      decomposition for the cross-correlation function of doubly stochastic point
      processes, where each of the components corresponds precisely to the concepts of
      dependence under investigation. This allows us to correct the correlation
      function for rate effects, which implies that spike coordination and rate
      covariation are statistically separable concepts of dependence. Furthermore, we
      present direct and intuitive model implementations of the discussed concepts and
      illustrate that their difference is not a matter of timescale. Analysis of data
      generated by our models and analytical description of the relevant estimators
      reveals, however, that spike coordination dramatically influences the accuracy of
      rate covariance estimation. As a consequence, extreme parameter combinations can
      lead to situations where the concept of dependence cannot be identified
      empirically. However, for a wide range of parameters, the concept of dependence
      underlying a given data set can be identified regardless of its timescale.

PMID- 18336078
TI  - Spike train probability models for stimulus-driven leaky integrate-and-fire
      neurons.
AB  - Mathematical models of neurons are widely used to improve understanding of
      neuronal spiking behavior. These models can produce artificial spike trains that
      resemble actual spike train data in important ways, but they are not very easy to
      apply to the analysis of spike train data. Instead, statistical methods based on
      point process models of spike trains provide a wide range of data-analytical
      techniques. Two simplified point process models have been introduced in the
      literature: the time-rescaled renewal process (TRRP) and the multiplicative
      inhomogeneous Markov interval (m-IMI) model. In this letter we investigate the
      extent to which the TRRP and m-IMI models are able to fit spike trains produced
      by stimulus-driven leaky integrate-and-fire (LIF) neurons. With a constant
      stimulus, the LIF spike train is a renewal process, and the m-IMI and TRRP models
      will describe accurately the LIF spike train variability. With a time-varying
      stimulus, the probability of spiking under all three of these models depends on
      both the experimental clock time relative to the stimulus and the time since the
      previous spike, but it does so differently for the LIF, m-IMI, and TRRP models.
      We assessed the distance between the LIF model and each of the two empirical
      models in the presence of a time-varying stimulus. We found that while lack of
      fit of a Poisson model to LIF spike train data can be evident even in small
      samples, the m-IMI and TRRP models tend to fit well, and much larger samples are
      required before there is statistical evidence of lack of fit of the m-IMI or TRRP
      models. We also found that when the mean of the stimulus varies across time, the
      m-IMI model provides a better fit to the LIF data than the TRRP, and when the
      variance of the stimulus varies across time, the TRRP provides the better fit.

PMID- 18336079
TI  - Temporal dynamics of rate-based synaptic plasticity rules in a stochastic model
      of spike-timing-dependent plasticity.
AB  - In a recently proposed, stochastic model of spike-timing-dependent plasticity, we
      derived general expressions for the expected change in synaptic strength, DeltaS
      n, induced by a typical sequence of precisely n spikes. We found that the rules
      DeltaS n, n >or= 3, exhibit regions of parameter space in which stable,
      competitive interactions between afferents are present, leading to the activity
      dependent segregation of afferents on their targets. The rules DeltaS n, however,
      allow an indefinite period of time to elapse for the occurrence of precisely n
      spikes, while most measurements of changes in synaptic strength are conducted
      over definite periods of time during which a potentially unknown number of spikes
      may occur. Here, therefore, we derive an expression, DeltaS(t), for the expected
      change in synaptic strength of a synapse experiencing an average sequence of
      spikes of typical length occurring during a fixed period of time, t. We find that
      the resulting synaptic plasticity rule Delta S(t) exhibits a number of remarkable
      properties. It is an entirely self-stabilizing learning rule in all regions of
      parameter space. Further, its parameter space is carved up into three distinct,
      contiguous regions in which the exhibited synaptic interactions undergo different
      transitions as the time t is increased. In one region, the synaptic dynamics
      change from noncompetitive to competitive to entirely depressing. In a second
      region, the dynamics change from noncompetitive to competitive without the second
      transition to entirely depressing dynamics. In a third region, the dynamics are
      always noncompetitive. The locations of these regions are not fixed in parameter
      space but may be modified by changing the mean presynaptic firing rates. Thus,
      neurons may be moved among these three different regions and so exhibit different
      sets of synaptic dynamics depending on their mean firing rates.

PMID- 18336080
TI  - Temporal coding: assembly formation through constructive interference.
AB  - Temporal coding is studied for an oscillatory neural network model with
      synchronization and acceleration. The latter mechanism refers to increasing
      (decreasing) the phase velocity of each unit for stronger (weaker) or more
      coherent (decoherent) input from the other units. It has been demonstrated that
      acceleration generates the desynchronization that is needed for self-organized
      segmentation of two overlapping patterns. In this letter, we continue the
      discussion of this remarkable feature, giving also an example with several
      overlapping patterns. Due to acceleration, Hebbian memory implies a frequency
      spectrum for pure pattern states, defined as coherent patterns with decoherent
      overlapping patterns. With reference to this frequency spectrum and related
      frequency bands, the process of pattern retrieval, corresponding to the formation
      of temporal coding assemblies, is described as resulting from constructive
      interference (with frequency differences due to acceleration) and phase locking
      (due to synchronization).

PMID- 18336081
TI  - Adaptive integration in the visual cortex by depressing recurrent cortical
      circuits.
AB  - Neurons in the visual cortex receive a large amount of input from recurrent
      connections, yet the functional role of these connections remains unclear. Here
      we explore networks with strong recurrence in a computational model and show that
      short-term depression of the synapses in the recurrent loops implements an
      adaptive filter. This allows the visual system to respond reliably to
      deteriorated stimuli yet quickly to high-quality stimuli. For low-contrast
      stimuli, the model predicts long response latencies, whereas latencies are short
      for high-contrast stimuli. This is consistent with physiological data showing
      that in higher visual areas, latencies can increase more than 100 ms at low
      contrast compared to high contrast. Moreover, when presented with briefly flashed
      stimuli, the model predicts stereotypical responses that outlast the stimulus,
      again consistent with physiological findings. The adaptive properties of the
      model suggest that the abundant recurrent connections found in visual cortex
      serve to adapt the network's time constant in accordance with the stimulus and
      normalizes neuronal signals such that processing is as fast as possible while
      maintaining reliability.

PMID- 18336082
TI  - Oscillations and spiking pairs: behavior of a neuronal model with STDP learning.
AB  - In a biologically plausible but computationally simplified integrate-and-fire
      neuronal population, it is observed that transient synchronized spikes can occur
      repeatedly. However, groups with different properties exhibit different periods
      and different patterns of synchrony. We include learning mechanisms in these
      models. The effects of spike-timing-dependent plasticity have been known to play
      a distinct role in information processing in the central nervous system for
      several years. In this letter, neuronal models with dynamical synapses are
      constructed, and we analyze the effect of STDP on collective network behavior,
      such as oscillatory activity, weight distribution, and spike timing precision. We
      comment on how information is encoded by the neuronal signaling, when synchrony
      groups may appear, and what could contribute to the uncertainty in decision
      making.

PMID- 18336083
TI  - Recoding patterns of sensory input: higher-order features and the function of
      nonlinear dendritic trees.
AB  - Here analytical and simulation results are presented characterizing the recoding
      arising when overlapping patterns of sensor input impinge on an array of model
      neurons with branched thresholded dendritic trees. Thus, the neural units
      employed are intended to capture the integrative behavior of pyramidal cells that
      sustain isolated Na(+) or NMDA spikes in their branches. Given a defined set of
      sensor vectors, equations were derived for the probability of firing of both
      branches and neurons and for the expected overlap between the neural firing
      patterns triggered by two afferent patterns of given overlap. Thus, both the
      sparseness of the neural representation and the orthogonalization of overlapping
      vectors were computed. Simulations were then performed with an array of 1000
      neurons comprising 30,000 branches to verify the analytical results and confirm
      their applicability to systems (which include any practicable artificial system)
      in which the combinatorically possible branches and neurons are severely
      subsampled. A means of readout and a measure of discrimination performance were
      provided so that the accuracy of discrimination among overlapping sensor vectors
      could be optimized as a function of neuron structure parameters. Good performance
      required both orthogonalization of the afferent patterns, so that discrimination
      was accurate and free of interference, and maintenance of a minimum level of
      neural activity, so that some neurons fired in response to each sensor pattern.
      It is shown that the discrimination performance achieved by arrays of neurons
      with branched dendritic trees could not be reached with single-compartment units,
      regardless of how many of the latter are used. The analytical results furnish a
      benchmark against which to measure further enhancements in the performance of
      subsequent simulated systems incorporating local neural mechanisms which, while
      often less amenable to closed-form analysis, are ubiquitous in biological neural
      circuitry.

PMID- 18336084
TI  - An interview with David Newman, D.Phil. interviewed by Vicki Glaser.

PMID- 18336085
TI  - Optimization and utilization of the SureFire phospho-STAT5 assay for a cell-based
      screening campaign.
AB  - The family of signal transducers and activators of transcription (STATs) consists
      of seven transcription factors that respond to a variety of cytokines, hormones,
      and growth factors. STATs are activated by tyrosine phosphorylation, which
      results in their dimerization and translocation into the nucleus where they exert
      their effect on transcription of regulated target genes. The phosphorylation of
      STATs is mediated mainly by Janus kinases (JAKs). The JAK/STAT pathway plays a
      critical role in hematopoietic and immune cell function. Here we focus on one
      member of the STAT family, STAT5. STAT5 is phosphorylated by several JAKs,
      including Jak3, Jak2, and Tyk2, in response to interleukin-2, erythropoietin
      (EPO), and interleukin-22, respectively. Activation of STAT5 is essential to T
      cell development and has been associated with hematologic malignancies.
      Therefore, the ability to assess STAT5 phosphorylation is important for discovery
      efforts targeting these indications. The assay formats available to detect
      phosphorylated STAT5 (pSTAT5) are relatively low throughput and involve lengthy
      protocols. These formats include western blot analysis, enzyme-linked
      immunosorbent assay (ELISA), and flow cytometry. The SureFire (Perkin Elmer,
      Waltham, MA) pSTAT5 assay is a homogeneous assay that utilizes AlphaScreen
      (Perkin Elmer) technology to detect pSTAT5 in cell lysates. We have used this
      assay format to evaluate EPO-induced STAT5 phosphorylation in HEL cells and
      successfully complete a small-scale screening campaign to identify inhibitors of
      this event. The results obtained in these studies demonstrate that the SureFire
      pSTAT5 assay is a robust, reliable assay format that is amenable to high
      throughput screening (HTS) applications.

PMID- 18336086
TI  - ATLAS--a high-throughput affinity-based screening technology for soluble
      proteins: technology application using p38 MAP kinase.
AB  - Abstract: A general affinity-based screening assay for discovery of lead
      compounds binding to potential protein drug targets that is based upon protein
      thermal unfolding and aggregation is described. ATLAS (Any Target Ligand Affinity
      Screen) (Anadys Pharmaceuticals, Inc., San Diego, CA) is a simple, homogeneous,
      and high-throughput affinity-based screening technology that can identify
      compounds that bind and protect the target protein from thermal unfolding,
      denaturation, and subsequent aggregation. ATLAS detection of thermally unfolded
      and aggregated hexahistidine [(His)6]-tagged proteins uses time-resolved
      fluorescence resonance energy transfer between two anti-(His)6 antibodies,
      labeled with either a donor or acceptor fluorophore, that are simultaneously
      bound to the aggregated protein. The ATLAS assay is simple to perform and easily
      automated for screening large compound libraries. The technology is applicable to
      lead discovery for soluble proteins of known and unknown functions, and
      particularly for proteins that are difficult to assay functionally. The ATLAS
      technology has been evaluated using p38 mitogen-activated protein (MAP) kinase as
      the target protein. Known inhibitors of p38 MAP kinase were examined by ATLAS and
      a functional assay; the results showed good correlation between the two methods.

PMID- 18336087
TI  - Identification of ligand binding by protein stabilization: comparison of ATLAS
      with biophysical and enzymatic methods.
AB  - ATLAS (Any Target Ligand Affinity Screen) (Anadys Pharmaceuticals, Inc., San
      Diego, CA) is a homogeneous, affinity-based high-throughput screening technology
      based on protein thermal denaturation and the ability of ligands to bind and
      stabilize the target protein from unfolding. To further understand the assay
      sensitivity for the identification of ligands that bind to soluble protein
      targets, firefly luciferase was chosen to characterize the technology. Luciferase
      is a multidomain protein with a complex unfolding pathway. Binding of ATP results
      in a stabilizing conformational rearrangement of the domains. Using luciferase to
      characterize the ATLAS technology allowed us to evaluate the generality of the
      screening method for the identification of ligand binding to any target.
      Luciferase inhibitors identified from functional screens were used to assess the
      capability of ATLAS to rank order inhibitors. Comparison of the ATLAS 50%
      effective concentration with other biophysical and biochemical methods offered
      insight into optimizing ATLAS assay conditions to maximize sensitivity to
      compound binding and protein stabilization. The results show the importance of
      characterizing the thermal unfolding and aggregation behavior of the protein to
      allow the ATLAS screen to be optimally designed.

PMID- 18336088
TI  - Evaluation of dynamic mass redistribution technology for pharmacological studies
      of recombinant and endogenously expressed g protein-coupled receptors.
AB  - The Epic cell assay technology (Corning Inc., Corning, NY) uses a resonant
      waveguide grating optical biosensor to measure cellular response to ligands
      manifested through dynamic mass redistribution (DMR) of cellular contents. The
      DMR measurement is a noninvasive, label-free assay that can be used to assess the
      pharmacological properties of compounds. In this study, a panel of 12 compounds
      was evaluated against two G protein-coupled receptor (GPCR) targets in
      recombinant expressed cell lines using the Corning Epic system in 384-well
      microplates. The evaluation was performed in a double-blinded fashion such that
      the identity and properties of both the GPCR targets and compounds were unknown
      to the researchers at the time of the study. Analysis of the DMR response from
      cell stimulation was used to identify compounds that functioned as agonists or
      antagonists and to evaluate the associated efficacy and potency. DMR results were
      shown to have good agreement with data obtained from cyclic AMP and calcium flux
      assays for compounds evaluated. A further analysis was performed and successfully
      identified the signaling pathways that the two GPCRs activated. In addition, the
      DMR measurement was able to detect responses from an endogenous receptor in these
      cells. The Epic DMR technology provides a generic platform amenable to
      pharmacological evaluation of cellular responses to GPCR activation in a label
      free live cell assay format.

PMID- 18336089
TI  - An automated liquid chromatography-mass spectrometry process to determine
      metabolic stability half-life and intrinsic clearance of drug candidates by
      substrate depletion.
AB  - An automated process is described for the detailed assessment of the in vitro
      metabolic stability properties of drug candidates in support of pharmaceutical
      property profiling. Compounds are incubated with liver microsomes using a robotic
      liquid handler. Aliquots are taken at various time points, and the resulting
      samples are quantitatively analyzed by liquid chromatography-mass spectrometry
      utilizing ion trap mass spectrometers to determine the amount of compound
      remaining. From these data metabolism rates can be calculated. A high degree of
      automation is achieved through custom software, which is employed for instrument
      setup, data processing, and results reporting. The assay setup is highly
      configurable, allowing for any combination of up to six user-selected time
      points, variable substrate concentration, and microsomes or other biologically
      active media. The data, based on relative substrate depletion, affords an
      estimate of metabolic stability through the calculation of half-life (t(1/2)) and
      intrinsic clearance, which are used to differentiate and rank order drug leads.
      In general, t(1/2) is the time necessary for the metabolism, following first
      order kinetics, of 50% of the initial compound. Intrinsic clearance is the
      proportionality constant between rate of metabolism of a compound and its
      concentration at the enzyme site. Described here is the setup of the assay, and
      data from assay test compounds are presented.

PMID- 18336091
TI  - Flow-assisted surgical cerebral revascularization.
AB  - Extracranial-intracranial bypass surgery has advanced from a mere technical feat
      to a procedure requiring careful patient selection and a justifiable decision
      making paradigm. Currently available technologies for flow measurement in the
      perioperative and intraoperative setting allow a more structured and analytical
      approach to decision making. The purpose of this report is to review the use of
      flow measurement in cerebral revascularization, presenting algorithms for flow
      assisted surgical planning, technique, and surveillance.

PMID- 18336092
TI  - [Twenty years means nothing...!].

PMID- 18336093
TI  - [Is Kt/V the dialysis dose best indicator?].

PMID- 18336094
TI  - [K-DOQI guidelines for calcium and phosphorus metabolism in chronic kidney
      disease: outcomes, compliance and new drugs for treatment].

PMID- 18336095
TI  - [Magnesium in chronic kidney disease].

PMID- 18336096
TI  - [The transition of epithelial cells to fibromyoblasts. Mechanisms involved and
      its possible relationship with renal fibrosis].

PMID- 18336097
TI  - [Reality and future in the treatment of advanced chronic renal disease].

PMID- 18336098
TI  - [Alterations in bone mineral metabolism in patients with calcium kidney stone
      disease and polymorphism of vitamin D receptor. Preliminary results].
AB  - Bone health, within calcium kidney stone disease is a matter of controversy. On
      the other hand, some genetic studies have shown an association between some
      Vitamin D receptor polymorphisms and calcium kidney stone disease. MAIN
      OBJECTIVE: To study the possible association between calcium kidney stone disease
      with bone metabolism and some Vitamin D receptor polymorphisms. PATIENTS AND
      METHODS: This is a case-control study, with seventy-two subjects of both genders
      divided into two groups: Group I: cases, composed by 51 patients suffering from
      calcium kidney stone disease. Twenty-four of them had no hypercalciuria, 16 had
      absortive hypercalciuria and 11 had renal hypercalciuria. Group II: controls,
      composed by 21 people, without either urolithiasis or hypercalciuria. We
      performed a complete study including biochemical markers of bone mineral
      remodelling, bone mineral density (BMD) was estimated both in the lumbar spine
      (L2-L4) and femoral neck, and also VDR polymorphism for the loci b, a and t.
      RESULTS: Patients with urolithiasis had lower values of BMD both in the lumbar
      spine and femoral neck, compared to controls. Z-score were lower in the lumbar
      spine and femoral neck (p =0,045 y 0,031, respectively). Those patients with
      absorptive hypercalciuria had higher BMD in the femoral neck than those with
      renal hypercalciuria and non-hypercalciuria. Because they had more weight and
      height all the statistical study was performed alter adjusting by these two
      variables and statistical significance was then only stated between patients with
      hypercalciuria and without it. Patients with urolithiasis had higher values of
      1,25 (OH)2 vitamin D (p=0,002), and lower of PTH (p=0,049), without any
      relationship to hypercalciuria and its subtypes. Seventy six percent of the
      patients had a daily calcium intake lower than 800 mg/day. The distribution of
      VDR alleles in patients with urolithiasis was similar to controls, although after
      grouping genotypes, a lower distribution of BB and tt polymorphisms were observed
      in patients suffering from urolithiasis. CONCLUSIONS: Calcium kidney stone
      disease by itself produces a decrease in BMD, more intense in femoral neck,
      independently the presence or absence of hypercalciuria. Patients suffering from
      urolitihiasis have higher values of 1,25 (OH)2 vitamin D than non-hypercalciuric
      patients and lower values of PTH probably due to a low dietary calcium intake. In
      our population studied there is no relationship between VDR polymorphisms and the
      presence of calcium kidney stone disease. Because the reduced number of patients
      of our study, more studies are needed to obtain definitely conclusions.

PMID- 18336099
TI  - [Our experience in primary hyperaldosteronism].
AB  - The aim of this paper is to analyze the ways of appearance, clinical
      characteristics, diagnosis and treatment related to patients suffering from
      primary hyperaldosteronism (HA1 masculine) in external nephrology consultation
      since their opening. METHODOLOGY: a retrospective study was carried out, checking
      out all HA1 masculine diagnosed patients of clinical records from 1981-2005.
      RESULTS: 35 patients were diagnosed, with an average age of 50 and a predominance
      of men (82%). The main reason for starting the HA1 masculine study was persistent
      hypertension; other reasons were hypertension and hypopotassemia (34%). Sixteen
      of the cases were adenomas (7 classic adenomas and 9 renin-dependents) and
      fourteen of them were hyperplasia (10 bilateral hyperplasias and 4 primary
      adrenals hyperplasia). Five cases were excluded because they were waiting for
      complementary tests. For location diagnosis, gammagrafia I131cholesterol was the
      test showing more agreement with final diagnosis, and then RMN and TAC. In eight
      of the cases, an adrenal vein sampling was made. Ten of sixteen adenomas suffered
      a surgery performance. The result showed standardization of tensional levels,
      without any treatment in 60% of the cases. The rest of them are currently treated
      with spironolactone under an appropriate tensional control. Gynecomastia was the
      most usual adverse effect found. CONCLUSION: Contrary to other published papers,
      we found out a male predominance in our database. A similar incidence of adenomas
      e hyperplasias was obtained. The most usual way of appearance was persistent
      hypertension to treatment. Adenomas surgery does not imply healing results,
      though it achieves a better tensional levels control, using less drugs and
      diminishing aldosterone levels. It implies a descent in myocardic and vascular
      toxicity.

PMID- 18336100
TI  - [Synaptopodin immunoexpression in steroid-responsive and steroid-resistant
      minimal change disease and focal segmental glomerulosclerosis].
AB  - BACKGROUND AND OBJECTIVES: Synaptopodin is protein of podocytes, and a part of
      the actin-based contractile apparatus of foot-processes. Recently, proteins
      expressed by the podocyte were found to be important for the integrity of the
      glomerular filtration barrier. Podocytes are injured in many forms of
      glomerulopathies, including minimal change disease (MCD) and focal segmental
      glomerulosclerosis (FSGS). The study was undertaken to determinate if
      synaptopodin immunoexpression in renal tissue specimens differs between patients
      with steroid-responsive MCD, steroid-resistant MCD, and FSGS. METHODS:
      Synaptopodin immunoexpression was evaluated by immunoperioxidase staining with a
      mouse anti-human monoclonal antibody in 12 renal biopsy specimens in patients
      with steroid-responsive MCD, 10 renal tissues in steroid-resistant MCD, and in 14
      renal biopsy specimens in patients with FSGS. As a control 10 tissue specimens of
      the kidneys removed because of trauma were used. Synaptopodin expression was
      quantified as a percentage of glomerular tuft by computerized image analysis
      system. RESULTS: In normal controls synaptopodin immunoexpression was seen in
      podocytes along the glomerular basement membrane in a finely linear pattern. No
      changes were found in synaptopodin immunoexpression in steroid-responsive MCD
      versus controls. In patients with steroid-resistant MCD and FSGS a granular
      pattern of synaptopodin immunoexpression was seen. Areas of sclerosis in patients
      with FSGS did not demonstrate synaptopodin expression. Statistical analysis
      showed significantly diminished synaptopodin immunoexpresion in glomeruli in
      patients with steroid-resistant MCD and FSGS as compared with steroid-responsive
      MCD group and controls. Moreover, in renal tissues in patients with FSGS the
      immunoexpression of synaptopodin was decreased in comparison with renal biopsies
      in patients with steroid-resistant MCD. IN CONCLUSIONS: our results suggest that
      abnormal distribution and reduced expression of synaptopodin may be associated
      with poor response to steroid therapy in MCD and FSGS.

PMID- 18336101
TI  - [Occult renal failure in primary care. A women's problem?].
AB  - BACKGROUND: Chronic renal failure is becoming a public health problem. The
      estimation of glomerular filtration rate (GFR) using the MDRD-4 equation is
      important to find out patients with impaired renal function. The aim of this
      study was to determinate the rate of patients took care in Primary Care with
      "occult" renal failure, defined as a GFR less than 60 mL/min/1.73m2, and serum
      creatinine levels in the normal range of the laboratory (< 1.3 mg/dL for men, and
      < 1.2 mg/dL for women). METHODS: Patients over 18 years-old took cared in Primary
      Care of the health area of Plasencia (Caceres), who were measured serum
      creatinine level between March to July 2006. We estimated GFR using MDRD-4
      formula and classified the level of kidney function according to the NKF-DOQI
      guidelines. RESULTS: We estimated GFR in 13.784 analyses. In 1.042 the GFR was
      less than 60 mL/min/1.73m2, from 960 patients (6.96%). Mean age 76.8 years (range
      40-98 years). 418 keep normal serum creatinine levels (43.5%). CONCLUSION: Renal
      impairment seems to be prevalent in the general population took care in Primary
      Care. An elevated rate of patients with renal failure present serum creatinine
      levels in the laboratory normal range, "occult" renal failure. The systematic
      estimation of GFR using MDRD formula is necessary to detect this patients with
      renal impairment.

PMID- 18336102
TI  - [Multidetector row CT in assessment of coronary artery calcification on
      hemodialisis].
AB  - Vascular calcification is a strong predictor of cardiovascular and all-cause
      mortality. Coronary artery calcification is more frequent, more extensive and
      progresses more rapidly in CKD than in general population. They are also
      considered a marker of coronary heart disease, with high prevalence and
      functional significance. It suggests that detection and surveillance may be
      worthwhile in general clinical practice. New non-invasive image techniques, like
      Multi-detector row CT, a type of spiral scanner, assess density and volume of
      calcification at multiple sites and allow quantitative scoring of vascular
      calcification using calcium scores analogous to those from electron-beam CT. We
      have assessed and quantified coronary artery calcification with 16 multidetector
      row CT in 44 patients on hemodialysis and their relationship with several
      cardiovascular risk factors. Coronary artery calcification prevalence was of 84 %
      with mean calcium score of 1580 +/- 2010 ( r 0-9844) with calcium score > 400 in
      66% of patients. It was usually multiple, affecting more than two vessels in more
      than 50%. In all but one patient, left anterior descending artery was involved
      with higher calcium score level at right coronary artery. Advanced age, male,
      diabetes, smoking, more morbidity, cerebrovascular disease previous, and calcium
      binders phosphate and analogous vitamin D treatment would seem to be associated
      with coronary artery calcification. Coronary artery calcification is very
      frequent and extensive, usually multiple and associated to modifiable risk
      factors in hemodialysis patients. Multi-detector-row CT seems an effective,
      suitable, readily applicable method to assess and quantify coronary artery
      calcification.

PMID- 18336103
TI  - [Sclerosing encapsulating peritonitis: a latent threat. Changes of posture in
      surgery treatment].
AB  - Sclerosing Encapsulating Peritonitis (SEP) is a rare but serious complication of
      continuous ambulatory peritoneal dialysis (CAPD) with a high morbi-mortality. We
      describe our experience with patients was diagnostic of SEP, their
      characteristics in CAPD and their clinic evolution after diagnosis. 190 CAPD
      patients were follow-up during 17 years. Eight patients (4.2%) developed SEP.
      Average age 45+/-14 years (range 29-64 years), four was male. Time in CAPD was
      72+/-29 months (range 24-120 months). All patients have peritonitis previously
      (mean 3+/-1). We observe a change in peritoneum characteristics (D/P Cr 4), with
      an average of 0.6+/-0.1 at one year of CAPD, versus 0.82+/-0.08 at the end of
      CAPD, with statistic significance (p<0.001). There are increases in use of
      hypertonic bags: 53%+/-28 at beginning versus 91%+/-27 at end, with statistic
      significance (p<0.009). All patients show tendency to hyperphosphoremia (mean
      6.7+/-0.7 mg/dl), with product calcium-phosphorus 68.4+/-8.3. Five patients
      (62.5%) have a previous renal transplant, one lost due to early graft thrombosis
      and two lost due to acute rejection. Six patients (75%) have a previous abdominal
      surgery, although was extra peritoneal in all cases. The diagnosis of SEP was
      clinic suspicion in all cases, suggestive radiological data (intestinal handle
      group) and laparoscopy showing SEP (cocoon) with histological confirmation
      (fibrosis and peritoneal calcification) in four cases. The treatment was medical
      in six cases associated with surgery in four of them. The medical treatment was
      tamoxifen and/or corticosteroids, associated with total parenteral nutrition in
      two patients and enteral nutrition in one. Surgery in six patients: three as
      urgent surgery (all died) and three as programme surgery (two live still).
      Etiology of died was: three for sepsis, one for peritonitis after bowel
      perforation, one for severe problems of nutrition. The average survival of three
      patients alive was 38+/-17 months, two of them had programme surgery, and one
      with functioning transplant we opt for conservative treatment. The actuarial
      survival at 24 months was 51%. CONCLUSION: The SEP is a serious entity with high
      mortality. Although our short experience doesn't can indicate a concrete
      treatment, our personal impression is that early surgery associated with
      corticosteroids treatment may improve the prognostic.

PMID- 18336104
TI  - [How can we improve symptomatic hypotension in hemodialysis patients: cold
      dialysis vs isothermic dialysis].
AB  - BACKGROUND: Symptomatic hypotension is the most frequent acute complication
      affecting patients during chronic hemodialysis treatment sessions. Many reports
      have demonstrated that the use of cool dialysate has a protective effect on blood
      pressure during hemodialysis treatments. In the present study, we investigated
      whether preventing the hyperthermic response had favourable effects on
      hemodynamic stability during the hemodialysis procedure while affording good
      tolerance to patients. METHODS: We investigated the effect of thermal control of
      dialysate on hemodynamic stability in hypotension-prone patients in our center.
      Patients were eligible for the study if they had symptomatic hypotensive episodes
      (> 3/12session/ month) during the screening phase. The study was designed with
      two phases for the same selected patients and two treatment arms, each phase
      lasting 4 weeks. In the first phase, we adjusted dialysate temperature on 36
      masculineC for 12 sessions (cold dialysis) and in the second phase we used a
      device allowing the regulation of thermal balance (Blood Temperature Monitor;
      Fresenius Medical Care, Bad Homberg, Germany), that keep body temperature
      unchanged (isothermic dialysis). RESULTS: Nine HD patients were enrolled and
      completed the study. During the screening phase the mean ultrafiltration was 4 1%
      of dry weight, and blood pressure decreased from 9916 to 8016 mm Hg (p<0.001). In
      5.01.7 sessions of 12 treatments were complicated by hypotension. In the first
      and second phase we observed a decrease of complicated treatments with
      symptomatic hypotension (5.01.7 versus 2.71.6 y 2.81.7; p<0.01). Both procedures:
      Cold dialysis and Isothermic dialysis was well tolerated by patients. CONCLUSION:
      Results show that active control of body temperature can significantly improve
      intradialytic tolerance in hypotension-prone patients.

PMID- 18336105
TI  - [Clinical and analytical changes in hemodialysis without acetate].
AB  - BACKGROUND: the purpose of this study was to evaluate blood acetate levels and
      its correlation with clinical and analytical changes in hemodialysis patients
      treated with standard bicarbonate dialysate compared to treatment with acetate
      free bicarbonate dialysate. METHODS: fourteen patients on hemodialysis (11 male)
      with mean age of 61 15 years, were treated with conventional bicarbonate
      dialysate for 1 month and then switched to acetate-free bicarbonate dialysate for
      another month. Blood samples were drawn at the third session of first and fourth
      week of each type of dialysis. RESULTS: Pre-dialysis blood acetate levels were
      similar in both groups, whereas post-dialysis blood acetate levels were higher in
      patients treated with conventional bicarbonate dialysate (0.48+/- 0.64 vs. 0.18+/
      0.23 mmol/L, p=0.024). Moreover, both periods had similar percentage of patients
      with pre-dialysis blood acetate levels in the pathologic range, whereas this
      percentage was higher in post-dialysis samples from patients treated with
      conventional bicarbonate dialysate respect to acetate-free dialysate (67% vs.
      21%, p=0.001). Serum levels of interleukin-6 were statistically higher in the
      period with conventional bicarbonate dialysate (31.7+/- 24.7 vs. 18.7+/- 10.3
      pg/ml, p=0.014), even though other inflammatory markers such as LBP, TNF- and CRP
      failed to increase in the same period. We didn't found significant differences in
      the other parameters studied except for the changes in serum concentrations of
      sodium, chloride and bicarbonate. CONCLUSIONS: Acetate-free bicarbonate dialysate
      does not expose patients to a big amount of acetate and allows that the majority
      of patients finished hemodialysis with blood acetate levels in the physiologic
      ranges. Acetate-free dialysate was safe and well tolerated by our hemodialysis
      patients, although clinical advantages derived from its use should be evaluated
      in long-term prospective studies.

PMID- 18336106
TI  - [Multiple sclerosis and nephrotic syndrome in minimal change disease].
AB  - The coinciding suffering of two or more autoimmune diseases has been occasionally
      reported during the last years. We report a multiple sclerosis case in a young
      male patient who presented minimal-change nephrotic syndrome with frequent
      relapses seven months later. New relapses have been prevented with cyclosporine
      therapy in a dose of 3,8 mg/kg bw/day associated to prednisone 10 mg/day during
      eighteen months. Documentation and investigation of such cases will help to the
      best understanding of the immunopathogenesis of those diseases.

PMID- 18336107
TI  - [Giant renal arteriovenous malformation: a suspicious bruit].
AB  - Arteriovenous (AV) malformations remain relatively rare clinical lesions
      consisting in abnormal shunts between the arterial and venous vascular systems.
      Both,congenital or acquired fistulas, are unusual causes of renal or heart
      failure. Congenital AV fistulas usually present with hematuria, while acquired
      ones are more likely to present with hemodynamic changes, such as hypertension,
      cardiomegaly and congestive heart failure. Here we present a 61 year-old woman
      studied before by probable pulmonary arteriovenous fistula and referred to
      nephrologist with a six-month history of dyspnea and peripheral edema. Physical
      examination was remarkable for an apical systolic ejective murmur as well as
      another bruit over the right pulmonary base. Blood tests showed a sCr of 1.7
      mg/dl with normal urinalysis. On imaging, renal duplex ultrasound showed a
      pulsatile hiliar mass on the right kidney with an arterial flow of 300 cm/sec
      that was identified as a giant AV fistula on MRA. An echocardiogram revealed
      severe pulmonary hypertension with a cardiopulmonary output of 12,9 l/min that
      doubled the systemic one (6,49 l/min). In view of the large size of the AV
      fistula occupying the majority of the parenchyma, endovascular approach was
      turned down and a laparoscopic nephrectomy was performed successfully. There was
      an immediate clinical improvement and 45 days after the procedure, a control
      echocardiogram showed normalization of the cardiopulmonary parameters with
      minimal changes in glomerular filtration rate.

PMID- 18336108
TI  - [Heparin immune thrombocytopenia in a hemodialysis patient. A case report.
      Literature review].
AB  - Heparin-induced thrombocytopenia (HIT) is an important side effect of heparin
      therapy associated with significant morbidity and mortality if unrecognized. The
      platelet count typically falls below 150,000/ll 5-14 days after heparin is
      started. Thrombosis is the major clinical complication. We present the case gives
      a patient that develops a deep vein thrombosis ilio-femoral left, with
      trombocytopenia, one week after beginning treatment with haemodialysis in which
      Ac anti heparin is detected by test PaGIA (Particle Gel Inmuno Assay.

PMID- 18336109
TI  - [Nephrotic syndrome associated with minimal-change glomerulonephritis and chronic
      lymphocytic leukaemia].

PMID- 18336110
TI  - [Total calcification in a nonfunctioning transplanted kidney].

PMID- 18336111
TI  - [Immunoglobulin therapy and IgA nephropathy].

PMID- 18336112
TI  - The periodicity of vascular access thrombosis revisited: TIS the season.

PMID- 18336113
TI  - [Subacute renal failure as a form of presentation of Al-amyloidosis].

PMID- 18336114
TI  - [Encapsulating sclerosing peritonitis].

PMID- 18336115
TI  - [Diagnosis of interstitial nephropathy caused by BK virus in renal
      transplantation. Therapeutic management with cidofovir plus probenecid].

PMID- 18336116
TI  - [Inferior vena cava thrombosis in patient with IgA glomerulonephritis].

PMID- 18336117
TI  - [Nephrotic syndrome in bone marrow transplantation].

PMID- 18336118
TI  - [Severe gastrointestinal involvement caused by late CMV: the importance of early
      treatment].

PMID- 18336119
TI  - [Calculating glomerular filtration].

PMID- 18336121
TI  - [Goals for Nefrologia in a new era].

PMID- 18336122
TI  - [When and how to treat patients with membranous glomerulonephritis?].

PMID- 18336123
TI  - [Fabry's disease: a form of chronic renal disease that may be diagnosed and
      treated].

PMID- 18336124
TI  - [Uremic calcifying ateriolopathy (calciphylaxis) with metabolic syndrome and
      diabetes mellitus. The current perspective].

PMID- 18336125
TI  - [Post-surgery fluid therapy: the debate on tonicity is still open].

PMID- 18336126
TI  - [Hemodialysis dose. Difficulty in measuring it].

PMID- 18336127
TI  - [Placing the elderly undergoing hemodialysis in the spotlight].

PMID- 18336128
TI  - [Calciphylaxis: fatal complication of cardiometabolic syndrome in patients with
      end stage kidney disease].
AB  - Calciphylaxis characterized by schemic skin ulceration due to subcutaneous small
      arterioles calcification, is a rare disease but usually fatal. Disorders of
      calcium metabolism and vascular calcifications are common in dialysis patients
      but calciphylaxis prevalence is low in patients with end stage renal disease. So
      we proposed other emergent factors implicated in calciphylaxis development.
      METHODS: We studied retrospective 8 patients who developed calciphylaxis in our
      service from january 2001 to december 2006. RESULTS: All patients were female
      with mean age at diagnosis 68.5+/-6.7 years. All patients were receiving
      hemodialysis therapy and 6 patients had been receiving hemodialysis less than
      four months. Six patients had diabetes mellitus type II and all patients were
      obese (BMI >25 kg/m2). All patients had metabolic syndrome (APTIII) with bad
      control hypertension and 6 (75%) were receiving anticoagulation therapy with
      warfarin. Patients didn t have severe alterations of calcium metabolism, all had
      product calcium-phosphorus <55. All patients developed low blood pressure at the
      beginning of dialysis treatment (98.3+/-22.7/60+/-18,29 mmHg). 7 patients present
      proximal lesions in fatty regions like abdomen and thighs. Histopathologic
      examination reveals calcium deposits in arteriole-sized and small vessels with
      vascular thrombosis. Prognosis was poor, seven patients died secondary to a
      sepsis originated in infected cutaneous ulcers. CONCLUSIONS: calciphylaxis is a
      disease with poor prognosis and high mortality, without specific treatment
      actually. Female gender, obesity associated with diabetes mellitus and
      cardiometabolic syndrome, anticoagulant therapy with warfarin and low blood
      pressure associated with hemodialysis therapy, are risk factors to develop
      calciphylaxis, in absence of severe disorders of calcium metabolism. In these
      patients is important to avoid hypotension episodes during dialysis, dialysis
      hypotension appears to be an important risk factor who promotes ischemia of
      subcutaneous adipose tissue.

PMID- 18336129
TI  - [Fluid therapy in surgical patients: composition and influences on the internal
      milieu].
AB  - Intravenous fluids administration is the usual practice in the postoperative
      period. Nonetheless, consensus about the more appropriate fluid reposition recipe
      is still insufficient. OBJECTIVE: To study the type of intravenous reposition
      used in Surgical Units and its impact on the internal milieu. PATIENTS AND
      METHODS:  DESIGN: prospective study of 112 patients with scheduled surgery,
      receiving only intravenous fluids. METHODS: biochemical study on postoperative
      fluids management in uncomplicated surgery. Principal variables: 1. Water and
      electrolytes administrated. 2. Differences in sodium/water balances before
      surgery vs first day after surgery. 3. Symptoms related to hyponatremia. RESULTS:
      Median P[Na] before and after surgery was 139.9+/-2.9 and 137.7+/-3.7,
      respectively (p<0.01). Fourteen patients (12.5%) had P[Na]<135, and 12 of them
      had a reduction of more than 6 mmol/L; accordingly, twenty-six patients (23.2%)
      had an increased free-water retention (p<0.05). Relevantly, they did not receive
      a higher amount of free-water and the proportion of isotonic saline/free water
      varied from <1 to >3. As possible mechanism of free-water accumulation: the
      postoperative P[Na] was lower in the patients who had a negative free-water
      clearance >or= -1 L (136.7+/-4.1 vs 138.5+/-3.2 mmol/L, p 0.015). CONCLUSION: The
      present study provides new information about the intravenous fluids prescribed in
      postoperative patients, ie, different proportions saline/water are basically
      equivalent with respect to inducing symptomatic hyponatremia. The mean value of
      the relation saline/water is 2:1. Hypotonic fluids input is not clearly related
      to more intense hyponatremia; the latter appears to depend more on a reduced
      capacity of the kidney to generate sufficient free water output.

PMID- 18336130
TI  - [Kt as control and follow-up of the dose at a hemodialysis unit].
AB  - To ensure our patients are receiving an adequate dose in every dialysis session
      there must be a target to achieve this in the short or medium term. The
      incorporation during the last years of the ionic dialysance (ID) in the monitors,
      has provided monitoring of the dialysis dose in real time and in every dialysis
      session. Lowrie y cols., recommend monitoring the dose with Kt, recommending at
      least 40 L in women and 45 L in men or individualizing the dose according to the
      body surface area. The target of this study was to monitor the dose with Kt in
      every dialysis session for 3 months, and to compare it with the monthly blood
      test. 51 patients (58% of our hemodialysis unit), 32 men and 19 women, 60.7+/-14
      years old, in the hemodialysis programme for 37.7+/-52 months, were dialysed with
      a monitor with IC. The etiology of their chronic renal failure was: 3 tubulo
      interstitial nephropathy, 9 glomerulonephritis, 12 vascular disease, 7 polycystic
      kidney disease, 7 diabetic nephropathy and 13 unknown. 1,606 sessions were
      analysed during a 3 month period. Every patient was treated with the usual
      parameters of dialysis with 2.1 m2 cellulose diacetate (33.3%), 1.9 m2
      polisulfone (33.3%) or 1.8 m2 helixone, dialysis time of 263+/-32 minutes, blood
      flow of 405+/-66, with dialysate flow of 712+/-138 and body weight of 66.7+/-14
      kg. Initial ID, final ID and Kt were measured in each session. URR and Kt/V were
      obtained by means of a monthly blood test. The initial ID was 232+/-41 ml/min,
      the final ID was 197+/-44 ml/min, the mean of Kt determinations was 56.6+/-14 L,
      the mean of Kt/V was 1.98+/-0.5 and the mean of URR was 79.2+/-7%. Although all
      patients were treated with a minimum recommended dose of Kt/V and URR when we
      used the Kt according to gender, we observed that 31% of patients do not get the
      minimum dose prescribed (48.1+/-2.4 L), 34.4% of the men and 26.3% of the women.
      If we use the Kt individualized for the body surface area, we observe that 43.1%
      of the patients do not get the minimum dose prescribed with 4.6+/-3.4 L less than
      the dose prescribed. We conclude that the monitoring of dialysis dose with the Kt
      provides a better discrimination detecting that between 30 and 40% of the
      patients perhaps do not get an adequate dose for their gender or body surface
      area.

PMID- 18336131
TI  - [Epidemiological study on chronic renal failure elderly patients on
      hemodialysis].
AB  - Hemodialysis shows an increased prevalence in elderly patients, a population
      which often presents poor nutrition, high prevalence of cardiovascular,
      neurological and osteoarticular diseases and psycho-social problems. The
      objective of this epidemiological, cross-sectional and multicenter study, in
      patients older than 65 years (n 625) and >75 years (n 558) from 29 Spanish
      medical institutions was to perform an epidemiological analysis It included
      demographic information, as well as data regarding chronic renal failure,
      functional and psychological abilities (Katz Index, Lawton and Karnofsky Scales),
      dialysis logistics and clinical parameters. The study analyzed data from 1,183
      patients (678 female), mean age 75.4+/-5.5 years; mean duration of dialysis 4.3+/
      5.1 years (57.7% were referred by the GP: general practitioner). The most
      frequent etiologies were diabetic nephropathy (21.2%) and vascular renal disease
      (20.9%). The main comorbilites were high blood pressure (75.6%), Diabetes
      Mellitus (32.9%) and vascular (29.0%) and osteoarticular (27.3%) diseases. The
      great majority of patients lived at their family home (85.0%), travelled to their
      dialysis units alone (80.8%) and by ambulance (56.7%), and it took them less than
      an hour to arrive (87.5%). Over 75% of patients were fully functional (79.4%
      under 75 years and 71.6% over 75); meanwhile 10.5% were partially impaired and
      13,8% severely impaired. Karnofsky performance scale scored less than 70 in 59.4%
      of the patients. Analytical parameters rated Hb >or= 11 g/dL for 81.7% of
      patients; ferritin >or= 100 ng/dL for 98.5%; PTH 150-300 pg/mL for 31.9%; albumin
      >3.5 g/dL for 75.6%; and serum phosphor <5.5 mg/dL for 70.6%. For the dialysis
      Kt/V the mean value was 1.4+/-0.3 with a mean duration of dialysis session of
      11.7+/-4.0 hours/week. High permeability membranes were used in 52.3% of patients
      and internal arteriovenous fistula in 74.0%. Around 75% of elderly patients on
      hemodialysis fulfill age-suitable daily living activities and display adequate
      dialysis quality parameters.

PMID- 18336132
TI  - [Irbesartan in hypertensive non-diabetic advanced chronic kidney disease.
      Comparative study with ACEI].
AB  - Angiotensin-converting enzyme inhibitors (ACEI) have proved an antihypertensive
      and renoprotective effect with reduction of proteinuria in diabetic and non
      diabetic nephropathy, but not exempt of side effects in advanced chronic kidney
      disease (ACKD) patients. Angiotensin receptor blockers (ARB) have emerged as
      antiproteinuric, renoprotective and cardioprotective therapy. Only a few reports
      have been published studying ARB effects on non-diabetic ACKD patients. Our aim
      is to study Irbesartan (ARB) on non-diabetic ACKD patients and compare its
      effects with ACEI. PATIENTS AND METHODS: Forty three non-diabetic patients at
      ACKD stage IV NKF-DOQI (CrCl <30 ml/min) were enrolled in a prospective study.
      Group I: 21 received Irbesartan monodose 150-300 mg/day (63+/-17 y/o, 12 F, 9
      M,ClCr 22.1+/-8 ml/m.), Group II: 22 received ACEI (65+/-13 y/o, 8 F, 14 M, CrCl
      22.3+/-7 ml/m). Parameters studied: blood pressure (BP), pulse pressure (PP),
      renal function (CrCl), proteinuria (in patients with proteinuria >or= 0.5 g/d),
      serum K+ and serum uric acid, at month 0, 3, 6, 9 and 12. RESULTS: At 12 months,
      BP was controlled in 57% of Group I vs 39% of Group II. Mean systolic BP was
      decreased from 154/85 to 138/77 in G I, and from 146/85 to 133/77 in GII, with a
      decrease in 10.7% of mean BP in GI and 8.5% in GII (NS). Irbesartan reduced PP in
      7.2% vs 8.3% with ACEI (NS). CrCl reduction with Irbesartan was 0.23 vs 0.21
      ml/min/month with ACEI (NS). The antiproteinuric effect was higher with
      Irbesartan (from 2.1 to 1.3 g/day) vs. ACEI (from 1.35 to 1.33 gr /day), being
      statistically significant the reduction percentage between the two groups (p >or=
      0.041). Serum K+ level do not change in Irbesartan group and increased 10% in
      ACEI group (p<0.001). Uric acid was decreased by Irbesartan in 17% and increased
      in 4% by ACEI (p<0.001). CONCLUSIONS: Irbesartan in non-diabetics patients with
      advanced chronic renal disease, compared with ACEI showed similar blood pressure
      control and similar effect on chronic kidney disease progression, with higher
      antiproteinuric effect. On the other side, Irbesartan showed a reduction of serum
      uric acid, and did not increase serum K+ levels.

PMID- 18336133
TI  - [Safety and effectiveness of nicotinic acid in the management of patients with
      chronic renal disease and hyperlipidemia associated to hyperphosphatemia].
AB  - OBJECTIVE: To establish if the nicotinic acid in patients with chronic renal
      disease reduce significantly and with security the levels of lipids and serum
      phosphate in refractory patients to the classical management. DESIGN:
      Observational study Place: Renal Unity RTS Ltda Caldas Santa Sofia Hospital.
      PATIENTS: All the patients with chronic renal disease in dialysis therapy to whom
      the classical treatment for their hyperlipidaemia and hyperphosphatemia didn't
      manage a satisfactory reduce of their serum levels. METHODS: It was identified
      that those patients who in the 3 previous months to the intervention hadn't
      presented changes in the lipids profile even though they received low fats diet
      and a lipid lowering therapies (statin o fibric acid derivates). It was
      determined in them whether they presented levels of serum phosphorus greater than
      5.5 mg/dl even though having received nutritional recommendations and treatment
      with oral phosphate binding agents (Aluminum hydroxide, Calcium salts or
      Sevelamer). In them it was proceeded to administrate nicotinic acid via oral at
      night until a doses of 1,000 milligrams was reached (preceded of 100 mgs of
      acetylsalicylic acid 1 hour before) during a period of 8 months, observing its
      therapeutical effectivity and security profile to improve the lipids profile and
      reduce the serum phosphorus. RESULTS: 9 patients complied with the requirements,
      average time in dialysis 34 months, 3 in hemodialysis and 6 in peritoneal
      dialysis. All patients started with 500 mgs and 3 months later correctly
      tolerated the dose of 1,000 mgs. Between the evaluated variables, the most
      important changes were: the phosphorus reduced reaching a significant value at
      eight months: initial 6.46+/-0.53, four months 4.37+/-0.63 (p>0.05) and eight
      months 3.94+/-0.76 (p<0.01); the product Ca x P obtained important reductions at
      four and eight months; the total Cholesterol and Triglyceride was significant
      reduced at all periods, not being so for the LDL, although the HDL elevated to
      significant values at eight months. There were no significant modifications in
      the LDL cholesterol, intact PTH, hemoglobin, platelet count, hepatic function
      tests (AST, ALT and Bilirubin), coagulation tests (TTP and TP), uric acid,
      glycemic control, albumin, creatinine, BUN, % transferring saturation, ferritin,
      folic acid and Vitamin B12. No patient presented collateral or clinical effects
      of importance, being the adherence to the medicament 100%. CONCLUSIONS: The
      nicotinic acid is efficient, very well tolerated and economical in comparison
      with others drugs, which makes it ideal for the treatment of patients with
      hyperlipidaemia and refractory hyperphosphatemia to the classical treatments.

PMID- 18336134
TI  - [Physiotherapy during hemodialysis: results of a progressive resistance-training
      programme].
AB  - During the last decades, aerobic exercise programs have shown beneficial effects
      on quality of life of End Stage Renal Disease (ESRD) patients, but there is still
      little evidence on the benefits of resistance training programmes. The aim of
      this study was to analyze the effects of a short strengthening exercise program
      for ESRD during hemodialysis on exercise and functional capacity and on quality
      of life. METHODS: 16 hemodialysis patients were assigned, according to their own
      election, to exercise (N>or=8) or control group (N>or=8). The experimental group
      performed a 6-month duration intradialytic exercise program supervised by a
      physiotherapist, consisting of a battery of isometric and isotonic exercises for
      the lower limbs. Control group remained sedentary. A graded exercise test
      (Naughton protocol), functional measurements (<<6 minutes walking test>> 6MWT and
      'sit to stand to sit tests' STS-10 and STS-60), and the SF-36, to assess quality
      of life were measured pre and post intervention in the experimental group, while
      the control group only completed the SF-36 questionnaire. RESULTS: Considering
      the experimental group, both time and METS increased after the intervention,
      although it was not significant. Meters measured in the 6MWT significantly
      increased after the intervention (399.57+/-39.56 meters pre-intervention;
      471.71+/-70.63 meters post-intervention p<0.01). Both time on the STS-10 (22.52+/
      4.77 seconds pre-intervention; 17.71+/-1.79 seconds post-intervention p<0.05) and
      repetitions on the STS-60 (28.57+/-5.12 repetitions pre-intervention; 31.42+/
      2.443 repetitions post-intervention p<0.05) significantly improved after the
      intervention. After training, the mental component scale of the SF-36
      significantly increased in the experimental group compared to baseline (41.74+/
      9.25 before; 50.61+/-12.13 after, p<0.05), while the control group showed a
      significant decrease (48.19 +/- 16.1 before; 33.7+/- 13.8 after, p<0.05).
      Comparison between groups also showed a significant difference in the mental
      component scale after the intervention (p<0.05). CONCLUSION: It is concluded that
      a strengthening exercise program during hemodialysis improves the functional
      capacity of ESRD patients (walking and standing from a seat) and improves the
      mental component of quality of life perceived by dialysis patients.

PMID- 18336135
TI  - [Prognostic significance of hemoperitoneum in peritoneal dialysis].
AB  - According to previous reviews, hemoperitoneum episodes appear in 6.1-8.4% of the
      peritoneal dialysis patients, and they are severe in a 20% of them. Due to the
      absence of severe hemoperitoneum in our peritoneal dialysis program, we
      retrospectively reviewed hemoperitoneum non-related with abdominal surgery or
      catheter placing. We analyzed its incidence, etiology, prognostic and clinical
      outcome, as well as the possible effect of recurrent hemoperitoneum on peritoneal
      function. A total of 132 patients were treated in our centre during a period of
      173 months. Mean age at the beginning of peritoneal dialysis was 59+/-17.1 years,
      43.2% were females, and 22.8% of them were menstruating women. Twenty-two
      patients had at least one hemoperitoneum episode during follow-up, with an
      incidence of 17%. The mean time interval between the start of peritoneal dialysis
      and the first hemoperitoneum episode was 0.66+/-0.94 years (range: 0.01-3.20
      years). 73% were women. Most cases (59%) were due to menstruation. Remarkably,
      all the menstruating women presented hemoperitoneum at least once with a high
      incidence of recurrent episodes. The other hemoperitoneum episodes were mainly of
      unknown etiology (32% of patients), being this one the main cause in males. We
      only observed two more cases: a male who presented hemoperitoneum related to
      dicumarinic overdose and a female who presented hemoperitoneum due to mesenteric
      ischemia. All the 22 patients had a favourable outcome, except for the woman with
      mesenteric ischemia, what represented an incidence of 4.5% of severe
      hemoperitoneum. No significant association was found between episodes of
      hemoperitoneum and aspirin treatment, dicumarinic treatment or the presence of
      coagulopathy. There was no association either between recurrent hemoperitoneum
      and the number of peritonitis episodes, peritoneal function or technique
      survival. In conclusion, hemoperitoneum is a common and usually benign problem in
      peritoneal dialysis patients, frequently due to retrograde menstruation, and no
      deleterious long-term effects were found in patients with recurrent
      hemoperitoneum.

PMID- 18336136
TI  - [Axillary catheter for hemodialysis, an alternative vascular access].
AB  - OBJECTIVE: To establish if the implantation of catheters for hemodialysis in
      axillary veins is an acceptable alternative in patients with Acute or Chronic
      Renal Failure (ARF o CRF) with limitations for other type of central catheter.
      PLACE: Manizales City Hospital's Intensive Care Units and ambulatory procedure
      rooms of the Renal Unity RTS Ltda Caldas Subsidiary, Santa Sofia Hospital and
      Infantile Hospital. PATIENTS: All the patients with ARF or CRF, who required
      hemodialysis therapy, but that their pathology of base or the depletion of their
      classical access routes, required the implantation of catheters bilumenes by non
      conventional routes, during a period of 10 years that was extended from may 1997
      to may 2007. METHODS: Those patients with ARF or CRF that required tracheostomy
      as support for ventilation due to their base illness; and those with ARF or CRF
      in whom the ambulatory or intra-hospital implantation of a central catheter for
      hemodialysis was not possible were carefully identified. The implantation of a
      double lumen central catheter for hemodialysis in axillary vein by palpation or
      anatomical guide was offered as an alternative to both the patients and their
      families. The procedure was practiced to those that accepted and gave their
      written consent; radiologically confirming its location; establishing their
      functionability at the time, as well as the complications associated to the
      procedure and it permanency. RESULTS: 27 procedures were practiced in 26
      patients. Average age: 54.6 years; 9 women and 17 men. 7 of them had ARF and 19
      CRF. In two patients the axillary vein puncture was not possible. Of the 25
      axillary catheters that were implanted, 1 was permanent and 24 transitory. The
      technique was used by anatomical references in 16 patients and by palpation in 8.
      In the patients 15 left axillary veins were canalized unlike the remaining 10
      that were right axillary veins. 18 patients presented impossibility of obtaining
      an alternative central venous access (different to femoral) and 7 patients
      required tracheostomy. The radiological location was satisfactorily confirmed in
      24 procedures (96%). The amount of time the catheters were used was an average of
      68.6 days; 6 patients died with the catheter in use. The main cause for the
      catheter's removal was the transference to peritoneal dialysis. The axillary
      artery was accidentally punctured in 3 patients, one of whom presented a soft
      tissue hematoma without a major hemodynamics repercussion; this had a spontaneous
      resolution in a few weeks. The venous canalization was not possible in 3
      patients. CONCLUSIONS: The implantation of bilumenes catheters for hemodialysis
      in patients with ARF or CRF is a relatively safe alternative to consider when
      other classical routes have totally spent or the patients present tracheostomy.

PMID- 18336137
TI  - Mycophenolate mofetil in chronic glomerular diseases.

PMID- 18336138
TI  - [Systemic AA amyloidosis induced by benign neoplasms].
AB  - Amyloidosis is a systemic disorder characterized by the extracellular tissue
      deposition of insoluble, toxic aggregates in bundles of beta-sheet fibrillar
      proteins. These deposits are typically identified on the bases of their apple
      green birrefringence under a polarized light microscope after staining with Congo
      red, and by the presence of rigid, nonbranching fibrils 8 to 10 nm in diameter on
      electron microscopy. The type of amyloid fibril unit can be further defined by
      immunohistology or by immunoelectron microscopy. It has been described at least
      25 different human protein precursors of amyloid fibrils, which will describe its
      corresponding amyloid disease. The most common types of amyloidosis are AL
      (primary) and AA (secondary) types; the former, is the most frequent and is due
      to deposition of proteins derived from immunoglobulin light chain fragments,
      occurring alone or in association with multiple myeloma. The later (AA), is
      caused by deposition of fibrils composed of fragments of the acute phase reactant
      serum amyloid A (SAA) and complicates chronic diseases with ongoing or recurring
      inflammation, namely; rheumatoid arthritis (RA), juvenile chronic polyarthritis,
      ankylosing spondylitis, familial periodic fever syndromes (Familial Mediterranean
      Fever), chronic infections and furthermore, some neoplasms (mainly renal cell
      carcinoma and Hodgkin's disease). Despite its less frequent association, some
      benign neoplasms can subsequently complicate to AA amyloidosis, therefore, an
      early diagnose and successful treatment may lead indeed, to regression of the
      amyloid disease. Herein, we present two cases of AA amyloidosis, both of them
      caused by 2 different benign neoplasms: 1. A 34 year-old woman, after chronic
      oral contraceptive use, developed an hepatic adenoma (fig. 1) which finally lead
      to AA amyloidosis with primary kidney presentation (pure nephrotic syndrome)
      (table 1). Post-surgical complications yield to acute renal failure from which
      unfortunately could not be recovered. After being on hemodialysis therapy during
      10 months she received a first renal allograft without any complication. 2. A 20
      year old woman, was diagnosed of AA amyloidosis after a renal biopsy (fig. 2)
      because of nephrotic syndrome (table 1). Further investigation lead to the
      finding of a hialyne-vascular type Castleman's disease located in the
      retroperitoneum (fig. 2). Despite surgical resection and medical treatment
      (colchicine) she developed progressive renal failure requiring initialization of
      hemodialysis therapy. After 6 years being on hemodialysis, she received a first
      renal allograft which is currently functioning after one year of follow- up.
      Although other chronic inflammatory diseases complicate more frequently to AA
      amyloidosis, benign tumors have to be taken into account as a potential
      ethiological cause for secondary amyloidosis.

PMID- 18336139
TI  - [Control of hypertension refractory to medical management by means of short daily
      hemodialysis].
AB  - Hypertension is a very frequent complication in patients in hemodialysis. A high
      percentage of the patients on standard hemodialysis remain hypertense in spite of
      intensive pharmacologic treatment. We presented the case of a hypertense patient
      with difficult control in spite of antihypertensive treatment with five drugs and
      several secondary complications. The change to a short daily hemodialysis was
      successful to hypertension control and allowed a gradual suspension of drugs.

PMID- 18336140
TI  - [Efficacy of rasburicase therapy in obstructive renal failure secondary to
      urolithiasis: a novel therapeutic option].
AB  - The overall incidence of nephrolithiasis-related acute and chronic renal failure
      is poorly known and surely underestimated. However, obstructive nephropathy
      represents a potentially curable form of kidney disease that often requires for
      managing an instrumentation of urinary tract. Rasburicase is an enzyme that
      transforms uric acid to allantoin, a compound more water soluble that will be
      excreted by the kidney more easily. Rasburicase has been proven to be an
      effective therapy for prevention of tumour lysis syndrome. But it also represents
      an interesting new option in managing hyperuricemia in patients with severe
      tophaceous gout. We administered rasburicase intravenously (0.20 mg/kg/day, for 2
      days) in 2 adults with acute obstructive nephropathy from renal calculi, which
      was receiving temporary haemodialysis. Rasburicase produced a sharp polyuria 12
      18 hours after its administration accompanied with a fast reduction of serum
      creatinine levels, that returned to normal range without further dialysis. If we
      suppose that rasburicase can pass through glomerular filter by its relatively low
      molecular weight, it could dissolve tubular uric acid crystals in acute renal
      failure associated to tumour lysis syndrome, providing the restoration of renal
      function. But we also could postulate that rasburicase can act in urinary tract,
      fragmentating renal calculi, promoting relief of obstructive uropathy and the
      resolution of renal failure. We suggest rasburicase should be tried in this new
      indication to prove its potential efficacy.

PMID- 18336141
TI  - [Acute renal failure in a case of nephrotic syndrome secondary to focal and
      segmental glomerulosclerosis].
AB  - Nephrotic syndrome is infrequently complicated with appearance of acute renal
      failure and minimal change disease is the glomerulopathy more usually involved.
      Pathogenesis is unclear and three possible mechanisms it has been proposed to
      explain the decrease of glomerular filtration rate: a severe reduction of
      glomerular permeability, the presence of acute tubular necrosis or an increased
      intrarenal pressure related with interstitial oedema. Here we present a 36 years
      old-male with a nephrotic syndrome caused by focal and segmental
      glomerulosclerosis who developed an anuric acute renal failure. Renal function
      did not change despite oedema removal with haemodialysis and only after
      corticosteroid and cyclophosphamide therapy introduction we observed a rapid
      recovery of urinary output and resolution of acute renal failure. Renal biopsy
      did not show signs of tubular damage or obstruction with proteins nor significant
      interstitial oedema. Therefore, in this case we think acute renal failure was
      caused by a severe reduction in glomerular ultrafiltration rate and steroids were
      the effective treatment that allowed recovery of renal function.

PMID- 18336143
TI  - [Comments to the proposal for the use of indicators from the group of quality
      management of the SEN].

PMID- 18336144
TI  - [AA amyloidosis due to renal cell carcinoma in a horseshoe kidney].

PMID- 18336145
TI  - [Emphysematous cystitis in a patient with renal transplant].
AB  - We describe a renal transplant patient who developed an abdominal pain in the
      hypogastrium area and a urinary tract infection. An abdominal RX, and later, a
      computerized tomography showed an air collection in the bladder wall.
      Emphysematous cystitis is a rare complication of the urinary tract infection,
      more frequently in patients with diabetes mellitus. It is important to treat it
      since the beginning, so we can avoid several complications.

PMID- 18336146
TI  - [Effect of macrobiotic diet on the progression of diabetic nephropathy: report of
      a case].

PMID- 18336147
TI  - [Acute renal failure due to carnitine palmitoyl transferase deficiency].

PMID- 18336148
TI  - [Acute post-streptococcal glomerulonephritis in the elderly].

PMID- 18336149
TI  - [Hemoperitoneum and endocarditis].
AB  - The incidence of hemoperitoneum varies from 6% to 57% in premenopausal women.
      Bloody peritoneal dialysate may be the result of the peritoneal dialysis
      procedure or may be due to factors unrelated to renal disease. The Libman-Sacks
      endocarditis was described for the first time in 1924, is characterized for
      verrucous lesions in the surfaces valves and has been intimately associated with
      the presence of antiphospholipid antibodies. We send a case of a patient in
      program of Dialysis peritoneal that presented an Libman-Sacks endocarditis and
      hemoperitoneum.

PMID- 18336150
TI  - [Late-onset hemothorax after left jugular vein catheterization for hemodialysis].

PMID- 18336151
TI  - [Renal failure secondary to lymphoplasmocytic lymphoma-Walndesntrom's
      macroglobulinemia].

PMID- 18336152
TI  - [Intoxication with Averrhoa carambola in a patient on chronic dialysis].

PMID- 18336153
TI  - [Penis necrosis as an unusual manifestation of calciphylaxis in uremia].

PMID- 18336154
TI  - [Chyloperitoneum and amyloidosis].
AB  - Chyloperitoneum is very infrequent in peritoneal dialysis. It has been described
      in patients diagnosed of systemic amyloidosis. We present the case of a patient
      in program of peritoneal dialysis, with familial amyloidosis type Andrade disease
      that presented intermittent and recidivante chyloperitoneum.

PMID- 18336155
TI  - [Postpartum hemolytic uremic syndrome: a rare entity and a treatment challenge].
AB  - Hemolytic uremic syndrome (HUS) is a rare entity that in 7% of cases has been
      related to oral contraceptives, pregnancy and puerperium, In this clinical
      setting prognosis is worse and renal replacement therapy is usually needed.
      Different authors agree that plamapheresis is the treatment of choice, and has
      improved patient survival to 80-90%. We describe a case of a young woman that 10
      days postpartum developed thrombocytopenia, microangiopathic hemolytic anemia and
      acute renal failure with nephrotic range proteinuria. With the suspicion of HUS
      she was started on plasmapheresis initially stopped due to an anaphylactic
      reaction to plasma and finally due to hyperhidratation with acute pulmonary edema
      needing mechanical ventilation. Renal biopsy confirmed the diagnosis. Clinical
      course was complicated with refractory hypertension and infectious complications
      In conclusion postpartum HUS is a rare clinical entity , that forces a
      differential diagnosis with hypertensive complications of pregnancy. It is
      associated to multiple complications difficult to handle during follow-up.
      Plasmapheresis treatment adds complexity to clinical care but is the only
      treatment of proven efficacy in order to improve survival and renal prognosis.

PMID- 18336190
TI  - Apoptotic pathways as targets for therapeutic intervention.

PMID- 18336191
TI  - p53: a guide to apoptosis.
AB  - Approximately 50% of sporadic human tumors harbor somatic mutations in the p53
      gene locus, while germ line mutations confer a high familial risk and are
      associated with Li-Fraumeni Syndrome patients. The p53 tumor suppressor protein
      is often referred to as the "guardian of the genome" since its response to DNA
      damage or checkpoint failure gives rise to a series of anti-proliferative
      responses. One of the most important functions of p53 is its ability to induce
      apoptosis, while disruption of this route can promote tumor progression and chemo
      resistance. Besides its ability to promote apoptosis through transcription
      dependent mechanisms, p53 may also be able to activate apoptosis independent of
      transcriptional regulation. Therefore, to ensure normal cell growth, p53 levels
      and activity are tightly regulated. Upon diverse forms of cellular stress the
      steady state levels and transcriptional activity of p53 are considerably
      increased. The stabilization and activation of p53 are a result of hindered
      inhibition by its negative regulators, e.g. Mdmx (also known as Mdm4) and Mdm2,
      while on the other hand activators such as HIPK2 and DYRK2 enhance the p53
      response. The continually increasing understanding of the mechanisms of
      regulation of p53 may provide the basis for new drug designs that could
      eventually lead to therapeutics to reactivate p53 in cancers.

PMID- 18336193
TI  - Targeting IAP (inhibitor of apoptosis) proteins for therapeutic intervention in
      tumors.
AB  - Apoptosis, or programmed cell death, is a cell suicide process with a major role
      in development and homeostasis in vertebrates and invertebrates. Dysregulation of
      apoptosis leading to early cell death or the absence of normal cell death
      contributes to a number of disease conditions including neurodegenerative
      diseases and cancer. Inhibition of apoptosis enhances the survival of cancer
      cells and facilitates their escape from immune surveillance and cytotoxic
      therapies. Inhibitor of apoptosis (IAP) proteins, a family of anti-apoptotic
      regulators that block cell death in response to diverse stimuli through
      interactions with inducers and effectors of apoptosis are among the principal
      molecules contributing to this phenomenon. IAP proteins are expressed in the
      majority of human malignancies at elevated levels and play an active role in
      promoting tumor maintenance through the inhibition of cellular death and
      participation in signaling pathways associated with malignancies. Herein, the
      role of IAP proteins in cancer and strategies toward targeting IAP proteins for
      therapeutic intervention will be discussed.

PMID- 18336192
TI  - Targeting cell death in tumors by activating caspases.
AB  - Cytotoxic approaches to killing tumor cells, such as chemotherapeutic agents,
      gamma-irradiation, suicide genes or immunotherapy, have been shown to induce cell
      death through apoptosis. The intrinsic apoptotic pathway is activated following
      treatment with cytotoxic drugs, and these reactions ultimately lead to the
      activation of caspases, which promote cell death in tumor cells. In addition,
      activation of the extrinsic apoptotic pathway with death-inducing ligands leads
      to an increased sensitivity of tumor cells toward cytotoxic stimuli, illustrating
      the interplay between the two cell death pathways. In contrast, tumor resistance
      to cytotoxic stimuli may be due to defects in apoptotic signaling. As a result of
      their importance in killing cancer cells, a number of apoptotic molecules are
      implicated in cancer therapy. The knowledge gleaned from basic research into
      apoptotic pathways from cell biological, structural, biochemical, and biophysical
      approaches can be used in strategies to develop novel compounds that eradicate
      tumor cells. In addition to current drug targets, research into molecules that
      activate procaspase-3 directly may show the direct activation of the executioner
      caspase to be a powerful therapeutic strategy in the treatment of many cancers.

PMID- 18336194
TI  - Ubiquitylation and cancer development.
AB  - Ubiquitylation is an essential cellular process, and yet many cancer cells appear
      to be more reliant upon it than normal cells as they are surprisingly sensitive
      to proteasome inhibitors (PI) and proteasome inhibitor drugs are well tolerated
      in vivo. Several reviews have suggested that specific protein targets account for
      PI induced cell death, but fail to adequately explain why cancer cells are more
      sensitive than normal cells to PIs. We review the evidence for these models,
      focusing primarily on inducers of cell death including p53 and the pro-apoptotic
      Bcl-2 Homology proteins (BH3 proteins) and propose an additional hypothesis; that
      a tumour cell's abnormal physiology makes it particularly reliant upon the
      proteasome. This hypothesis is well supported in the case of Multiple Myelomas,
      that may produce large amounts of antibodies and are therefore under considerable
      ER strain and in turn particularly reliant upon the proteasome to clear the large
      numbers of misfolded proteins. We propose that other cell types, tumor or non
      tumour, that are already under ER stress, or its equivalent, maybe particularly
      susceptible to proteasome inhibitors.

PMID- 18336195
TI  - Tumor necrosis factor: renaissance as a cancer therapeutic?
AB  - Since the discovery of tumor necrosis factor (TNF)-alpha, researchers have
      pursued many approaches to harness the potency of TNF-alpha and TNF superfamily
      members to treat human cancers. Several ligands of the TNF superfamily, including
      TNF-alpha, lymphotoxin, FAS ligand (FasL), and APO2 ligand/TNF-related apoptosis
      inducing ligand (Apo2L/TRAIL) have been tested in various stages of clinical
      research for their anti-tumor efficacy. Moreover, several antibodies to TNF
      receptor (TNFR) superfamily members are now being explored as cancer
      therapeutics. Due to the toxicity associated with delivering TNF-alpha
      systemically at clinically relevant doses, more targeted methods are now seen as
      a likely alternative to provide a localized therapeutically effective dose of TNF
      alpha. In this review we revisit historical attempts to use TNF-alpha to treat
      human cancer, and put this into the context of more recent targeted strategies to
      circumvent TNF-alpha's systemic toxicity. We will attempt to integrate the
      results of pre-clinical and clinical trials with a concise synopsis of the TNF
      alpha signaling network, with the goal of reconciling our understanding of how
      the cell biology and tumor biology mechanistically relate.

PMID- 18336196
TI  - Modulation of TRAIL-induced apoptosis by HDAC inhibitors.
AB  - Triggering apoptosis, the cell's intrinsic death program, is a promising approach
      for cancer therapy. TNF-related apoptosis-inducing ligand (TRAIL), a member of
      the TNF superfamily of death inducing ligands, is of special interest for cancer
      therapy, since TRAIL has been shown to predominantly kill cancer cells, while
      sparing normal cells. However, since many cancers fail to undergo apoptosis in
      response to TRAIL treatment, TRAIL-based combination therapies have been
      developed for cancer-cell specific sensitization towards TRAIL. Chromatin
      remodelling plays an important role in gene regulation and aberrant architecture
      of the chromatin has been implicated in tumor formation and progression. In
      recent years, HDAC inhibitors (HDACI) that reverse aberrant epigenetic changes
      have emerged as a potential strategy to sensitize cancer cells for TRAIL-induced
      apoptosis. Synergistic tumor cell death has been reported in a variety of human
      cancers using different HDACI together with TRAIL. Here, recent advances in the
      understanding of the molecular events that underlie the synergistic interaction
      of HDACI and TRAIL are discussed as well as how this knowledge can be translated
      into the design of cancer-selective novel therapeutics.

PMID- 18336197
TI  - Application of proteome analysis to the assessment of prognosis and response
      prediction in clinical oncology.
AB  - In Europe more than 3 million individuals develop a malignancy annually. Despite
      recent progress in screening, diagnosis and therapy of most cancers, prognosis
      remains poor and only a minority of patients are cured. This owes to the fact
      that most cancers are diagnosed in advanced stages and due to the fact that
      treatment options for most cancers are limited. While there has been a
      substantial improvement in systemic therapy for many cancers it remains difficult
      to assess the potential responsiveness of the cancers towards these newly
      developed drugs, which include small molecules and monoclonal antibodies.
      Therefore various strategies have been developed in order to assess the prognosis
      and predict the expected tumor response in order to individualize the treatment,
      thereby offering the patient a tailored therapy which accounts for the tumor- and
      patient-specific morphological and molecular characteristics of the disease. This
      review summarizes recent efforts, challenges and limitations of proteome analysis
      in the assessment of prognosis and response-prediction in human cancers.

PMID- 18336198
TI  - Natural and synthetic agents targeting inflammation and angiogenesis for
      chemoprevention of prostate cancer.
AB  - Prostate cancer is the most common cancer in men and one of the leading causes of
      cancer-related deaths in Western countries. The extraordinary biological
      heterogeneity, the increasing incidence of this disease, and the presence of
      putative premalignant conditions make prostate cancer a crucial pathology to
      study and test pharmacological or nutritional chemopreventive strategies. It has
      been demonstrated that the incidence of prostate cancer is lower in Asian people,
      and that it increases in Asian men living in Western countries; these data point
      to a pivotal role of diet in the onset of prostate cancer. A large amount of work
      has been done in investigating chemopreventive properties of dietary compounds
      widely used in Asian countries (i.e. soy, soybeans, green tea, fish) in respect
      of the oxidants- and meat-rich diet typical of Western people, particularly of
      central and northern Europe. Some dietary products appear promising as chemo
      preventive agents for prostate cancer, because they display both anti-oxidant and
      anti-inflammatory activity - and inflammation is crucial for the aetiology of
      adeno-carcinoma of the prostate. There is increasing evidence for close
      correlation between inflammation, the microenvironment and tumour-associated neo
      angiogenesis causing the adverse outcomes of prostate cancer. It may thus be
      useful to develop new strategies to couple the treatment of inflammation-related
      prostate cancer and the generation of angiopreventive or antiinflammatory
      molecules to prevent this disease. The search for compounds with few or no
      adverse effects - particularly cardiovascular - as compared with the agents
      currently in use is therefore of greatest relevance.

PMID- 18336199
TI  - Novel monoclonal antibodies for the treatment of chronic lymphocytic leukemia.
AB  - For many years, alkylating agents and purine nucleoside analogs (PNA) have been
      considered the drug of choice for treatment of chronic lymphocytic leukemia
      (CLL). More recently the introduction of monoclonal antibodies (mAb), especially
      rituximab directed against CD20 and alemtuzumab directed against CD52, has
      renewed interest in CLL therapy. Over the last few years, several new mAbs
      directed against lymphoid cells have been developed and investigated in
      preclinical studies and clinical trials. Some of them are highly active in CLL.
      New mAbs directed against CD20 include human mAb ofatumumab (HuMax CD20), IMMU
      106 (hA20) which has a >90% humanized framework and GA-101, a novel third -
      generation fully humanized and optimized mAb. These agents are highly cytotoxic
      against B-cell lymphoid cells and are evaluated in CLL. Lumiliximab (anti-CD23
      mAb) is a genetically engineered macaque-human immunoglobulin (Ig) A1. This
      antibody showed high activity and good tolerability in phase I clinical trial and
      is evaluated in phase I/II clinical trials as a single agent and in combination.
      Epratuzumab is a humanized anti-CD22 mAb currently used in clinical trials for
      treatment of non-Hodgkin lymphoma and autoimmune disorders. Further studies are
      needed to elucidate the role of this agent in CLL. Apolizumab (HU1D10) is a
      humanized IgG1 antibody specific for a polymorphic determinant found on the HLA
      DRbeta chain. Preclinical and early clinical studies suggest that this mAb has
      some activity in CLL. HCD122 (CHIR-12.12) and SGN-40 are anti-CD40 mAbs which
      induce cytotoxicity against CLL cells. Phase I study has shown a favorable safety
      profile and some activity of HCD122 in pretreated CLL patients. Immunotoxins,
      especially BL22, LMP-2 and denileukin diftitox, are also being evaluated in
      lymphoid malignancies and seem to be active in CLL. Finally, antiangiogenic mAbs,
      especially bevacimzumab, have a potential therapeutic role in this disease. In
      this review, new mAbs, potentially useful in CLL are presented.

PMID- 18336201
TI  - Cominatorial chemistry & high throughput screening. Editorial from Guest Editors.

PMID- 18336202
TI  - The baculovirus display technology--an evolving instrument for molecular
      screening and drug delivery.
AB  - High throughput screening is a core technology in drug discovery. During the past
      decade, several strategies have been developed to screen (poly)peptide libraries
      for diverse applications including disease diagnosis and profiling, imaging, as
      well as therapy. The recently established baculovirus display vector system
      (BDVS) represents a eukaryotic screening platform that combines the positive
      attributes of both cell and virus-based display approaches, allowing presentation
      of complex polypeptides on cellular and viral surfaces. Compared to microbial
      display systems, the BDVS has the advantage of correct protein folding and post
      translational modifications similar to those in mammals, facilitating expression
      and analysis of proteins with therapeutic interest. The applicability of the
      system is further expanded by the availability of genetically engineered insect
      cell lines capable of performing e.g. mammalianized glycosylation in combination
      with high level of expression. In addition to insect cells, baculovirus can
      mediate delivery and expression of heterologous genes in a broad spectrum of
      primary and established mammalian cells. Currently, a variety of baculovirus
      based assays aiming at routine high throughput identification of agents targeting
      cell surface receptors or studies on ligand-receptor interactions are under
      construction. Here, the advancements and future prospects of the baculovirus
      display technologies with emphasis on molecular screening and drug delivery
      applications using insect cell display, mammalian cell display, and virion
      display are described.

PMID- 18336203
TI  - Retroviral display and high throughput screening.
AB  - Retroviruses distinguish themselves from all other mammalian viruses by their
      abilities to infect and propagate in mammalian cells without causing a cytopathic
      effect and to stably integrate their genetic information into the genome of the
      host cell. These unique properties make them an ideal platform for the display
      and directed evolution of proteins in a mammalian cell environment. This review
      will describe the essentials about retrovirus biology and then discuss in detail
      display and screening strategies that have been developed during the past 15
      years of retroviral display technology.

PMID- 18336204
TI  - Library selection approaches to engineering enhanced retroviral and lentiviral
      vectors.
AB  - Retroviral and lentiviral based gene delivery vectors have been used in numerous
      pre-clinical studies and clinical trials due to their advantages, including
      stable and prolonged expression of therapeutic transgenes and minimal immune
      responses against the vector. Despite such advantages, however, retroviral
      vectors also have several limitations for gene therapy applications. For example,
      they can suffer from a lack of efficient or targeted gene delivery to key cell
      types. In addition, retroviral vector stability can be compromised by their
      envelope proteins. This review briefly describes how such limitations have been
      overcome by recently developed library selection approaches that borrow a lesson
      from nature: the ability of evolution to generate biomolecules with novel
      function. These library selection approaches are based on the construction of
      retroviral libraries where the sequences encoding natural viral components are
      partially randomized using a variety of methods in order to generate diverse
      libraries that can be selected to create improved or novel functions. These high
      throughput, library-based approaches provide a strong complement to rational
      engineering of viral components for the rapid development of efficient and safe
      retroviral and lentiviral vector systems for gene therapy.

PMID- 18336205
TI  - Artificial evolution with adeno-associated viral libraries.
AB  - After attracting the attention of the scientific community due to a number of
      favourable characteristics that make it an attractive vector for human gene
      therapy [1,2], AAV has been thoroughly investigated in the past two decades.
      Standard technologies for the manipulation of the viral genome and for efficient
      packaging and purification protocols have paved the road for trial and error
      manipulation by educated guesses to study viral infectious biology by reverse
      genetics and to generate improved vectors for human gene transfer. However,
      despite remarkable progress, our limited knowledge of molecular mechanisms
      implicated in virus-cell interactions has been a limiting factor. Combinatorial
      engineering and high-throughput selection techniques hold the potential to boost
      technological improvement by offering the possibility to screen large numbers of
      randomly generated clones by appropriate selection protocols. These approaches
      not only require lesser knowledge of viral biology, but can also be employed as
      valuable tools to investigate molecular mechanisms that drive the infection
      process. In this review we recapitulate the rationale for employment of
      combinatorial methods in AAV vector development and the accomplishments achieved
      so far, discussing current limitations and interesting developments that are in
      sight.

PMID- 18336207
TI  - Peptide aptamer libraries.
AB  - Peptide aptamers are molecules that bind to protein targets and are able to
      interfere with their functions. In the past, important achievements have been
      made using such peptide aptamers in different approaches and for various
      purposes. Peptide aptamers are comprised of a variable peptide region of 8 to 20
      amino acids in length, which is displayed by a scaffold protein. An overview of
      the numerous scaffold proteins that have been investigated for their suitability
      to present peptide aptamers will be given. To identify peptide aptamers
      efficiently and specifically binding to a predetermined target, two eukaryotic
      systems have been used in multiple studies: a modified version of the Gal4 yeast
      two-hybrid system and the optimized LexA interaction trap system. The two yeast
      systems are compared and the design of high-complexity peptide aptamer libraries
      for these systems is described. Although the yeast-two-hybrid system is based on
      intracellular interactions mammalian screens, performed in cell culture
      experiments, are sometimes preferred or required. We will give an overview of the
      mammalian selection systems available, which are based on the expression of
      peptide aptamers in retroviral or lentiviral vectors. We will show that the
      isolation and use of peptide aptamers as inhibitors of individual signaling
      components represents a new challenge for drug development.

PMID- 18336206
TI  - A decade of yeast surface display technology: where are we now?
AB  - Yeast surface display has become an increasingly popular tool for protein
      engineering and library screening applications. Recent advances have greatly
      expanded the capability of yeast surface display, and are highlighted by cell
      based selections, epitope mapping, cDNA library screening, and cell adhesion
      engineering. In this review, we discuss the state-of-the-art yeast display
      methodologies and the rapidly expanding set of applications afforded by this
      technology.

PMID- 18336208
TI  - Rational design, selection and specificity of artificial transcription factors
      (ATFs): the influence of chromatin in target gene regulation.
AB  - Artificial Transcription Factors (ATFs) are engineered DNA-binding proteins
      designed to bind specific sequences of DNA. ATFs made of Zinc Finger (ZF) domains
      have been developed to regulate specific genes and phenotypes both in cells and
      whole organisms. Recently, an emerging application of engineered DNA-binding
      domains include the specific editing of the genome, the ability to specifically
      cut, recombine, modify DNA and image protein-nucleic acid interactions in living
      cells. In this review we will summarize the techniques used for the rational
      design, screening and functional selection of ZF proteins in mammalian cell
      systems and their applications in areas of biotechnology, functional genomics and
      molecular therapeutics. The in vivo specificity of the engineered ATFs will be
      discussed, with particular emphasis on epigenetic modifications influencing ATF
      DNA interactions.

PMID- 18336209
TI  - High throughput screening of gene functions in mammalian cells using reversely
      transfected cell arrays: review and protocol.
AB  - Reversely transfected cell microarrays (RTCM) have been introduced as a method
      for parallel high throughput analysis of gene functions in mammalian cells.
      Hundreds to thousands of different recombinant DNA or RNA molecules can be
      transfected into different cell clusters at the same time on a single glass slide
      with this method. This allows either the simultaneous overexpression or--by using
      the recently developed RNA interference (RNAi) techniques--knockdown of a huge
      number of target genes. A growing number of sophisticated detection systems have
      been established to determine quantitatively the effects of the transfected
      molecules on the cell phenotype. Several different cell types have been
      successfully used for this procedure. This review summarizes the presently
      available knowledge on this technique and provides a laboratory protocol.

PMID- 18336210
TI  - "Spirit" of high throughput screening.

PMID- 18336211
TI  - Discovery of novel targets with high throughput RNA interference screening.
AB  - High throughput technologies have the potential to affect all aspects of drug
      discovery. Considerable attention is paid to high throughput screening (HTS) for
      small molecule lead compounds. The identification of the targets that enter those
      HTS campaigns had been driven by basic research until the advent of genomics
      level data acquisition such as sequencing and gene expression microarrays. Large
      scale profiling approaches (e.g., microarrays, protein analysis by mass
      spectrometry, and metabolite profiling) can yield vast quantities of data and
      important information. However, these approaches usually require painstaking in
      silico analysis and low-throughput basic wet-lab research to identify the
      function of a gene and validate the gene product as a potential therapeutic drug
      target. Functional genomic screening offers the promise of direct identification
      of genes involved in phenotypes of interest. In this review, RNA interference
      (RNAi) mediated loss-of-function screens will be discussed and as well as their
      utility in target identification. Some of the genes identified in these screens
      should produce similar phenotypes if their gene products are antagonized with
      drugs. With a carefully chosen phenotype, an understanding of the biology of RNAi
      and appreciation of the limitations of RNAi screening, there is great potential
      for the discovery of new drug targets.

PMID- 18336212
TI  - Impact of novel screening technologies on ion channel drug discovery.
AB  - Ion channels are a large superfamily of membrane proteins that pass ions across
      membranes. They are critical to diverse physiological functions in both excitable
      and nonexcitable cells and underlie many diseases. As a result, they are an
      important target class which is proven to be highly "druggable". However, for
      high throughput screening (HTS), ion channels are historically difficult as a
      target class due to their unique molecular properties and the limitations of
      assay technologies that are HTS-amendable. In this article, we describe the
      background of ion channels and current status and challenges for ion channel drug
      discovery, followed by an overview of both conventional and newly emerged ion
      channel screening technologies. The critical impact of such new technologies on
      current and future ion channel drug discovery is also discussed.

PMID- 18336213
TI  - High throughput screening for orphan and liganded GPCRs.
AB  - GPCRs had significant representation in the drug discovery portfolios of most
      major commercial drug discovery organizations for many years. This is due in part
      to the diverse biological roles mediated by GPCRs as a class, as well as the
      empirical discovery that they have proven relatively tractable to the development
      of small molecule therapeutics. Publication of the human genome sequence in 2001
      confirmed GPCRs as the largest single gene superfamily with more than 700
      members, furthering the already strong appeal of addressing this target class
      using efficient and highly parallelized platform approaches. The GPCR research
      platform implemented at Amgen is used as a case study to review the evolution and
      implementation of available assays and technologies applicable to GPCR drug
      discovery. The strengths, weaknesses, and applications of assay technologies
      applicable to G alpha s, G alpha i and G alpha q-coupled receptors are described
      and their relative merits evaluated. Particular consideration is made of the role
      and practice of "de-orphaning" and signaling pathway characterization as a pre
      requisite to establishing effective screens. In silico and in vitro methodology
      developed for rapid, parallel high throughput hit characterization and
      prioritization is also discussed extensively.

PMID- 18336214
TI  - High-content analysis in preclinical drug discovery.
AB  - High-Content Analysis (HCA) has developed into an established tool and is used in
      a wide range of academic laboratories and pharmaceutical research groups. HCA is
      now routinely proving to be effective in providing functionally relevant results.
      It is essential to select the appropriate HCA application with regard to the
      targeted compound's cellular function. The cellular impact and compound
      specificity as revealed by HCA analysis facilitates reaching definitive
      conclusions at an early stage in the drug discovery process. This technology
      therefore has the potential to substantially improve the efficiency of
      pharmaceutical research. Recent advances in fluorescent probes have significantly
      boosted the success of HCA. Auto-fluorescent proteins which minimally hinder the
      functioning of the living cell have been playing a decisive role in cell biology
      research. For companies the severely restricted license conditions regarding auto
      fluorescent proteins hamper their general use in pharmaceutical research. This
      has opened the field for other solutions such as self-labeling protein
      technology, which could potentially replace the well established methods that
      utilize auto-fluorescent proteins. In addition, direct labeling techniques have
      improved considerably and may supersede many of the approaches based on fusion
      proteins. Following sample preparation, treated cells are imaged and the
      resulting multiple fluorescent signals are subjected to contextual and
      statistical analysis. The extraordinary advantage of HCA is that it enables the
      large-scale and simultaneous quantification and correlation of multiple
      phenotypic responses and physiological reactions using sophisticated software
      solutions that permit assay-specific image analysis. Hence, HCA once more has
      demonstrated its outstanding potential to significantly support establishing
      effective pharmaceutical research processes in order to both advance research
      projects and cut costs.

PMID- 18336215
TI  - Back to basics: label-free technologies for small molecule screening.
AB  - Small molecule high-throughput screening in drug discovery today is dominated by
      techniques which are dependent upon artificial labels or reporter systems. While
      effective, these approaches can be affected by certain experimental limitations,
      such as conformational restrictions imposed by the selected label or compound
      fluorescence/quenching. Label-free approaches potentially address many of these
      issues by allowing researchers to investigate more native systems without
      fluorescence- or luminescence-based readouts. However, due to throughput and
      expense constraints, label-free methods have been largely relegated to a
      supporting role as the basis of secondary assays. In this review, we describe
      recent improvements in impedance-based, optical biosensor-based, automated patch
      clamp and mass spectrometry technologies that have enhanced their ease of use and
      throughput and, hence, their utility for primary screening of small- to medium
      sized compound libraries. The ultimate maturation of these techniques will enable
      drug discovery researchers to screen large chemical libraries against minimally
      manipulated biological systems.

PMID- 18336217
TI  - High throughput screening informatics.
AB  - High throughput screening (HTS), an industrial effort to leverage developments in
      the areas of modern robotics, data analysis and control software, liquid handling
      devices, and sensitive detectors, has played a pivotal role in the drug discovery
      process, allowing researchers to efficiently screen millions of compounds to
      identify tractable small molecule modulators of a given biological process or
      disease state and advance them into high quality leads. As HTS throughput has
      significantly increased the volume, complexity, and information content of
      datasets, lead discovery research demands a clear corporate strategy for
      scientific computing and subsequent establishment of robust enterprise-wide
      (usually global) informatics platforms, which enable complicated HTS work flows,
      facilitate HTS data mining, and drive effective decision-making. The purpose of
      this review is, from the data analysis and handling perspective, to examine key
      elements in HTS operations and some essential data-related activities supporting
      or interfacing the screening process, and outline properties that various
      enabling software should have. Additionally, some general advice for corporate
      managers with system procurement responsibilities is offered.

PMID- 18336216
TI  - High throughput screening for neurodegeneration and complex disease phenotypes.
AB  - High throughput screening (HTS) for complex diseases is challenging. This stems
      from the fact that complex phenotypes are difficult to adapt to rapid, high
      throughput assays. We describe the recent development of high throughput and high
      content screens (HCS) for neurodegenerative diseases, with a focus on inherited
      neurodegenerative disorders, such as Huntington's disease. We describe, among
      others, HTS assays based on protein aggregation, neuronal death, caspase
      activation and mutant protein clearance. Furthermore, we describe high-content
      screens that are being used to prioritize hits identified in such HTS assays.
      These assays and screening approaches should accelerate drug discovery for
      neurodegenerative disorders and guide the development of screening approaches for
      other complex disease phenotypes.

PMID- 18336218
TI  - Recent advances in high throughput screening for ADME properties.
AB  - With the increase in the numbers of molecules synthesized in a typical drug
      discovery program, as well as the large amount of information utilized in the
      selection of a drug candidate, there is a need for a plethora of drug metabolism
      and pharmacokinetic (DMPK) information to be regularly generated in discovery.
      Over the past decade, many in vitro, and even in vivo, DMPK screens have been
      developed and routinely deployed to generate this information in support of drug
      discovery efforts. In the past few years, newer methods, or adaptations to
      methods, have been published, and this review attempts to summarize these
      advances. In particular, advances have been reported for experimental approaches
      to metabolic clearance, CYP inhibition, in vivo exposure, and distribution, as
      well as in silico determinations of absorption, distribution, metabolism, and
      excretion (ADME) properties. Bioanalytical approaches aimed at optimizing analyte
      method development, sample preparation, and analyte detection, have also been
      reported. Future advances will further improve the ability to make decisions on
      molecules earlier in drug discovery.

PMID- 18336219
TI  - Omics: an approach for drug targets.

PMID- 18336220
TI  - Clonetics.
AB  - Work on human immortalized cell lines is not considered research on human
      subjects, but does involve biohazards. It has also been estimated that about 80%
      of human cell lines are the kind of cells that they are expected. Cells that are
      cultured directly from a subject are referred to as primary cells. Clonetics is
      the term can be used to describe Human Immortalized Cell Lines. Using Clonetics,
      the process of drug discovery and development can be accelerated. It is expected
      to contribute to drug development in metabolic diseases. These can be
      successfully used in many medical treatments.

PMID- 18336221
TI  - Species scaling and extrapolation.
AB  - The various scaling methodologies and molecular features analysis were applied to
      new dataset to predict human pharmacokinetics studies. Whereas the predictive
      accuracies demonstrated across all of the various methodologies were lower for
      this higher clearance compound dataset, scaling from species continued to be an
      accurate methodology, and human volume of distribution was similarly well
      predicted regardless of scaling methodology. Also, extrapolation is the method
      for constructing new data points given a set of discrete data points. Methods
      estimate is reasonably reliable for short times, but for longer times, the
      estimate is liable to become less accurate. Species Scaling and Extrapolation are
      useful for acquiring toxicological data- epidemiological and experimental study.
      Animal studies help us to understand toxicity characteristics of a chemical
      before human exposure is allowed, whereas the epidemiological method generally
      does not. Species scaling and extrapolation from animals is necessary in many
      cases which helps in dealing with the so-called human risks more properly.

PMID- 18336222
TI  - Oncogenomics.
AB  - The rapid developments in the field of genomics and proteomics are expected to
      lead to a further increase in the potential for early diagnosis, the fine-tuning
      of prognostic features of specific tumors and the detection of cancer
      predisposition. Oncogenomics has identified new drug targets for genotype
      specific treatments and provided strategies to validate these targets and to
      develop drugs. With the potential need to stratify patients by genotype, clinical
      testing of targeted drugs has become more complicated while expectations of
      patients, investors, and funding agencies have become accelerated. Oncogenomics
      has progressed logically from molecular profiling to model systems, cancer
      pharmacology and clinical trials. Oncogenomics covers cutting-edge issues such as
      array-based diagnostics, pharmacogenomics, pharmacoproteomics and molecularly
      targeted therapeutics includes discussions of ethical, legal, and social issues
      related to cancer genomics and clinical trials.

PMID- 18336223
TI  - Pharmacogenomics.
AB  - Pharmacogenetics is the intersection of the fields of pharmacology and genetics.
      Simply stated, pharmacogenetics is the study of how genetic variations affect the
      ways in which people respond to drugs. These variations can manifest themselves
      as differences in the drug targets or as differences in the enzymes that
      metabolize drugs. A difference in the target will usually lead to differences in
      how well the drug works, whereas differences in metabolizing enzymes can result
      in differences in either efficacy or toxicity. It's also possible that genes not
      directly involved in a particular pathway could end up being predictive of
      clinical outcomes. Although pharmacogenomics has the potential to radically
      change the way health care is provided, it is only in its infancy. In the future,
      pharmacogenomics could find uses along the entire drug discovery and development
      timeline, all the way from target discovery and validation to late-stage clinical
      trials. Beyond that, pharmacogenomics tests could find their way into the
      doctor's office as a means to get the right medicine to the right patient at the
      right time. While genetics and genomics are often used synonymously,
      pharmacogenetics is more focused in scope than and is viewed as a subset of
      pharmacogenomics, which encompasses factors beyond those that are inherited.

PMID- 18336224
TI  - Proteomics: technologies for protein analysis.
AB  - Proteomics technologies have produced an abundance of drug targets, which is
      creating a bottleneck in drug development process. There is an increasing need
      for better target validation for new drug development and proteomic technologies
      are contributing to it. Identifying a potential protein drug target within a cell
      is a major challenge in modern drug discovery; techniques for screening the
      proteome are, therefore, an important tool. Major difficulties for target
      identification include the separation of proteins and their detection. These
      technologies are compared to enable the selection of the one by matching the
      needs of a particular project. There are prospects for further improvement, and
      proteomics technologies will form an important addition to the existing genomic
      and chemical technologies for new target validation. Proteomics is applicable for
      protein analysis and bioinformatics based analysis gives the comprehensive
      molecular description of the actual protein component. Bioinformatics is being
      increasingly used to support target validation by providing functionally
      predictive information mined from databases and experimental datasets using a
      variety of computational tools. This review is focused on key technologies for
      proteomics strategy and their application in protein analysis.

PMID- 18336225
TI  - Microarray: an approach for current drug targets.
AB  - Microarrays are a powerful tool has multiple applications both in clinical and
      cellular and molecular biology arenas. Early assessment of the probable
      biological importance of drug targets, pharmacogenomics, toxicogenomics and
      single nucleotide polymorphisms (SNPs). A list of new drug candidates along with
      proposed targets for intervention is described. Recent advances in the knowledge
      of microarrays analysis of organisms and the availability of the genomics
      sequences provide a wide range of novel targets for drug design. This review
      gives different process of microarray technologies; methods for comparative gene
      expression study, applications of microarrays in medicine and pharmacogenomics
      and current drug targets in research, which are relevant to common diseases as
      they relate to clinical and future perspectives.

PMID- 18336226
TI  - Epigenomics.
AB  - 'Epigenomics' can be termed as the study of the effects of chromatin structure,
      including the higher order of chromatin folding and attachment to the nuclear
      matrix, packaging of DNA around nucleosomes, covalent modifications of histone
      tails and DNA methylation. This has evolved to include any process that alters
      gene activity without changing the DNA sequence, and leads to modifications that
      can be transmitted to daughter cells. It also leads to a better knowledge of the
      changes in the regulation of genes and genomes that occur in major psychosis. It
      may also aid in understanding why the same gene sequence may predispose an
      individual to schizophrenia or bipolar disorder and in other cases does not, and
      elucidate the molecular mechanisms of how harmful; environmental factors interact
      with the genome. Results from the work may further lead to new diagnostics and
      effective therapies.

PMID- 18336227
TI  - Blood stage parasites: sufficient to induce protective immunity.
AB  - Merozoites are the surface antigens and variant antigens expressed on the surface
      of malaria-infected erythrocytes (including PfEMP1) are both targets of
      protective antibody responses. The mechanism of the modified immune response was
      observed after subpatent infections. Subpatently infected mice had increased
      antigen-specific T-cell responses; they were not better protected than patently
      infected mice. The study of human volunteers, the absence of detectable malaria
      specific antibodies probably reflects the extremely low parasite doses used for
      immunization. Induction of this type of immunity by immunizing with low doses of
      purified antigens from whole parasites may be an alternative but highly effective
      vaccine strategy.

PMID- 18336228
TI  - RNAi--a tool for target finding in new drug development.
AB  - RNAi (RNA interference) refers to the introduction of homologous double stranded
      RNA (dsRNA) to specifically target a gene's product, resulting in null or
      hypomorphic phenotypes. Long double-stranded RNAs (dsRNAs; typically >200 nt) can
      be used to silence the expression of target genes in a variety of organisms and
      cell types (e.g., worms, fruit flies, and plants). The long dsRNAs enter a
      cellular pathway that is commonly referred to as the RNA interference (RNAi)
      pathway. RNAi is being considered as an important tool not only for functional
      genomics, but also for gene-specific therapeutic activities that target the mRNAs
      of disease-related genes. RNAi plays a very important role in endogenous cellular
      processes, such as heterochromatin formation, developmental control and serves as
      an antiviral defense mechanism. RNAi has shown great potential for use as a tool
      for target finding in new drug development, molecular biological discovery,
      analysis and therapeutics. RNAi pathway is involved in post-transcription
      silencing, transcriptional silencing and epigenetic silencing as well as its use
      as a tool for forward genetics and therapeutics.

PMID- 18336229
TI  - Transcriptomics.
AB  - Transcriptomics, a genome-wide measurement of mRNA expression levels based on DNA
      microarray technology is one of the prominent fields of study. This is the term
      given to the set of all transcripts or messenger RNA (mRNA) molecules produced in
      cells. It can also be applied to the specific subset of transcripts present in a
      particular cell or the total set of transcripts in a given organism.
      Transcriptomics has evolved from a variety of already present technologies and
      areas. These areas include proteomics, genomics, and environmental science.

PMID- 18336230
TI  - Toxicogenomics.
AB  - Toxicogenomics is defined as an integration of genomics (transcriptomics,
      proteomics and metabolomics) and toxicology. It is a scientific field that
      studies how the genome is involved in responses to environmental stressors and
      toxicants. It combines studies of mRNA expression, cell and tissue-wide protein
      expression and metabonomics to understand the role of gene-environment
      interactions in disease. One of the important aspects of toxicogenomics research
      is the development and application of bioinformatics tools and databases in order
      to facilitate the analysis, mining, visualizing and sharing of the vast amount of
      biological information being generated in this field. This rapidly growing area
      promises to have a large impact on many other scientific and medical disciplines
      as scientists could now generate complete descriptions of how components of
      biological systems work together in response to various stresses, drugs, or
      toxicants.

PMID- 18336231
TI  - Kinomics.
AB  - Kinomics is derived from the word kinome that is the kinase part of the proteome.
      Kinomics is a merger between genomics and proteomics. Defining the kinase
      complement of the human genome, the kinome, has provided an excellent starting
      point for understanding the scale of the problem. This approach combines the
      understanding of small molecules and targets, and thereby assists the researcher
      in finding new targets for existing molecules or understanding selectivity and
      poly-pharmacology of molecules in related targets. Deciphering the complex
      network of phosphorylation-based signaling is necessary for a thorough and
      therapeutically applicable understanding of the functioning of a cell in
      physiological and pathological states.

PMID- 18336232
TI  - Physiomics.
AB  - Physiomics is that branch of omics that uses large scale databases and
      experimental databases along with computer algorithms to study the physiological
      phenotypes of genes, proteins and their relationships. It deals with studying the
      physiome, the total integration of genome, proteome and metabolome, from cells to
      organisms. It is a very useful branch that has been actively used in studying
      drug development, various interactions and biosensor as well as biochip
      development.

PMID- 18336233
TI  - Cytomics.
AB  - Cytomics is the branch of omics that takes into account the various bioinformatic
      techniques for understanding the functions and molecular architecture of the
      cytome. Cytomics, the multi-molecular cytometric analysis of the cellular
      heterogeneity of cytomes, access a maximum of information on the apparent
      molecular cell phenotype as it results from cell genotype and exposure. This has
      been done using various cytometrical procedures including microscopic techniques
      allowing the various components of a cell to be visualized as they interact in
      vivo.

PMID- 18336234
TI  - Murine atherosclerosis. Part III.
AB  - In this comprehensive collection of reviews of various aspects of atherosclerosis
      and atherosclerosis biology in mouse models, the first issue dealt with risk
      factors such as diet, genetics, gender, obesity, diabetes, hypertension,
      metabolic syndrome and acute inflammation. The second issue was devoted to many
      putative mechanisms contributing to atherosclerosis. Among the topics reviewed
      were: the interaction of modified lipoproteins with Toll-like receptors
      influencing atherosclerosis; the role of oxidative stress in the stimulating
      atherogenesis; the family of lipases (hepatic, lipoprotein, endothelial) produced
      by a variety of atherosclerosis relevant cells and capable of influencing
      lipoprotein homeostasis; the recruitment of blood cells to the vessel wall during
      atherogenesis; the central role of monocyte derived foam cells in
      atherosclerosis; the cytokines produced by the variety of cell types among innate
      and adaptive immune systems that influence atherosclerosis; the role of nuclear
      receptors in regulating lipoprotein metabolism and macrophage biology; the
      important effects of apoptosis of cells of the atherosclerotic lesions
      particularly in influencing the fate of these lesions; and the role of the
      adaptive immune system in regulating lipoprotein homeostasis and atherogenesis.

PMID- 18336236
TI  - Natural antibodies in murine atherosclerosis.
AB  - Natural antibodies are preformed antibodies that are present even in naive germ
      free mice in the absence of any exogenous antigenic exposure. Consistent with
      their specificities for microbial antigens, natural antibodies play an important
      non-redundant role in the first line defense against bacterial and viral
      infections. On the other hand natural antibodies have also been shown to have
      specificities for self antigens, and therefore have been proposed to provide
      important homeostatic "house-keeping" functions. Many of the recognized self
      antigens may in fact be stress-induced self-antigens, such as oxidation-specific
      epitopes that accumulate during atherogenesis as well as in many other
      inflammatory settings, and natural antibodies could protect from the impact of
      the pathological accumulation of these self-antigens. In this review we will
      discuss the specific example of the prototypic natural antibody T15/EO6, which is
      increased in atherosclerotic mice and mediates atheroprotection, and discuss the
      potential role of natural antibodies in atherogenesis in general.

PMID- 18336235
TI  - Lipoprotein size and susceptibility to atherosclerosis--insights from genetically
      modified mouse models.
AB  - High plasma levels of the apo-B-containing lipoproteins are casually implicated
      in the pathogenesis of atherosclerosis. This finding, backed by decades of animal
      and human studies, has sparked interest in defining which classes of apo-B
      containing lipoprotein particles are most atherogenic. Although small LDL
      particles and larger remnant lipoproteins both appear to be atherogenic, it has
      been difficult to discern which particles are the most atherogenic. Here, we
      summarize several mouse models that have provided insights into this issue. The
      influence of lipoprotein size on susceptibility to atherosclerosis was examined
      by studying the phenotypes of two strains of mice with virtually identical levels
      of plasma cholesterol--Ldlr(-/-)Apob(100/100) and Apoe(-/-) Apob(100/100) mice.
      The Ldlr(-/-) Apob(100/100) mice, where the cholesterol is in small LDL
      particles, had far more atherosclerosis than Apoe(-/-) Apob(100/100) mice, where
      virtually all of the cholesterol was in larger, VLDL-sized particles. Another
      intriguing animal model is the Gpihbp1-deficient mouse. GPIHBP1 is an endothelial
      cell platform for lipolysis, and mice lacking this protein have an accumulation
      of large, triglyceride-rich lipoproteins. Defining the extent of atherosclerosis
      in these mice should provide new insights into the atherogenicity of large,
      triglyceride-rich lipoproteins.

PMID- 18336237
TI  - Atheroprotective effects of HDL: beyond reverse cholesterol transport.
AB  - The risk of atherosclerosis is inversely related to circulating levels of high
      density lipoprotein (HDL) cholesterol. Notably, in large-scale epidemiologic
      studies, this association is independent of plasma levels of low density
      lipoprotein cholesterol levels. Pharmacologic agents, such as fibrates and niacin
      that increase HDL cholesterol levels have been associated with decreased
      cardiovascular events and beneficial effects on the coronary and carotid
      arteries. Furthermore, there is evidence that the risk of restenosis following
      vascular interventions is inversely related to HDL levels. This review considers
      the available data from mainly murine models on potential mechanisms by which HDL
      may exert these anti-atherogenic effects, namely through its role in reverse
      cholesterol transport, its effects on endothelial cells, and its anti
      inflammatory/anti-oxidant activities. In addition to discussing a role for HDL in
      retarding atherosclerosis progression, we will also review how HDL may play a
      role in promoting regression of atherosclerotic lesions.

PMID- 18336238
TI  - Apo A-1 mimetic peptides as atheroprotective agents in murine models.
AB  - The mouse has proven to be an excellent model for testing apolipoprotein mimetic
      peptides as agents to treat a variety of vascular inflammatory conditions
      including atherosclerosis, cognitive dysfunction associated with arteriole
      inflammation, chronic rejection of transplanted hearts, and scleroderma. The
      mechanism of action appears to relate to the ability of these peptides to
      preferentially bind pro-inflammatory oxidized lipids and is independent of the
      chirality of the peptides since peptides synthesized from either D- or L-amino
      acids appear to be equally effective.

PMID- 18336239
TI  - Progression and disruption of advanced atherosclerotic plaques in murine models.
AB  - The innominate artery is a predilection site for atherosclerotic lesion formation
      in hyperlipidemic mice. The lesions at this site in chow-fed apo E-/- mice
      progress from fatty streaks through stages that include atheroma with large
      necrotic areas, fibro-fatty nodules containing chondrocyte-like cells and highly
      calcified, acellular plaques. The advanced lesions in the innominate arteries of
      the apo E-/- mice exhibit a reproducible frequency of intra-plaque hemorrhage
      that occurs primarily as a result of fissures through lateral fatty streaks that
      form adjacent to or on top of the established plaques. However, this plaque
      disruption is not equivalent to plaque rupture in human lesions where there is
      rupture of well formed fibrous caps. The plaque disruption in the lesions of the
      chow-fed apo E-/- mice also do not lead to formation of occlusive thrombi, the
      predominant marker of plaque rupture in humans. Thus, although the lesions in the
      innominate arteries of hyperlipidemic mice progress to very advanced stages of
      the disease, they are not, in our opinion a model in which to study the
      mechanisms of plaque rupture in humans. The advanced lesions in the innominate
      arteries of the apo E-/- mice may however be adequate models for studying
      vascular fibrosis and calcification.

PMID- 18336240
TI  - Myocardial infarction following atherosclerosis in murine models.
AB  - The most widely used mouse models for atherosclerosis are LDL receptor knockout
      (KO) mice and apolipoprotein E (apoE) KO mice fed standard chow diets or lipid
      supplemented diets. Unfortunately, these do not usually exhibit myocardial
      infarction or other features of human cardiovascular disease such as occlusive
      coronary artery disease, cardiac dysfunction and/or reduced lifespan. Surgical
      models of myocardial infarction are successfully used for drug testing analyses
      during acute ischemia, but do not allow investigation of underlying mechanisms
      related to atherosclerotic coronary artery disease. Recently, experts in the
      pharmaceutical industry as well as some at the US Food and Drug Administration
      have identified inadequate animal models as being one of the major hurdles in
      drug discovery and development. There is an important need for additional well
      characterized, genetically manipulable, small animal models that mimic many
      features of human coronary heart disease (CHD), which would provide investigators
      in academia and in the pharmaceutical industry with a better system to unravel
      the pathophysiology of atherosclerotic CHD and to evaluate pre-clinical drug
      candidates. Here we will review recently developed mouse models of occlusive CHD,
      focusing on mice lacking expression of the HDL receptor, SR-BI in the context of
      reduced expression of apoE.

PMID- 18336241
TI  - Murine models of atherosclerotic calcification.
AB  - Vascular calcification is associated with increased cardiovascular morbidity and
      mortality and has long been associated with advanced atherosclerotic lesions.
      While vascular calcification is considered a surrogate marker for
      atherosclerosis, the mechanisms that link the two are poorly understood. The
      consensus of recent research is that active regulatory processes govern vascular
      calcification, and much focus has been placed on elucidating the phenomenon of
      atherosclerotic calcification. Building upon extensive in vitro work and the
      previous development of atherosclerotic murine models, several groups have
      developed murine models of atherosclerotic calcification. From imposing chronic
      renal failure to developing double-knockout mice, this recent work has provided
      insight into the pathophysiology of mineralized matrix formation in
      atherosclerotic lesions, as well as development of potential therapies to prevent
      or inhibit progression of calcified plaque. The aim is to briefly review current
      understanding of the molecular basis for atherosclerotic calcification and to
      discuss some murine models that may be useful in advancing knowledge of its
      mechanisms.

PMID- 18336242
TI  - The hemostasis system in murine atherosclerosis.
AB  - Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that
      progresses in discrete stages and involves a number of cell types and effector
      molecules. The potential importance of the coagulation, anticoagulation, and
      fibrinolytic systems in atherosclerosis is based on the observation that fibrin
      deposits and fibrin degradation products are resident in atherosclerotic plaques.
      A number of investigations have been conducted to probe the relationships between
      components of the hemostasis system and atherosclerosis; and these types of
      studies proliferated after the availability of mice genetically manipulated to
      emphasize the impact of genes of interest. In order to summarize recent progress
      in this area, this review is focused on mice lacking individual hemostasis genes
      and their contributions to steps of the atherosclerotic process.

PMID- 18336243
TI  - Vessel graft atherosclerosis in murine models.
AB  - The use of animal models in the study of arteriosclerosis is essential for better
      understanding of the pathogenesis, improvement in diagnosis, prevention and
      therapy of the diseases in humans. Recently numerous investigators started to use
      mouse models to study the pathogenesis of cardiovascular diseases. This species
      is particularly valuable which is believed to have some advantages over other
      strains, because of the availability of well-defined genetic systems of
      transgenic and knockout mice. Concomitantly, we have established the mouse models
      for vein grafts and transplant arteriosclerosis. By using these models, we have
      learned much knowledge concerning the pathogenesis of the disease and possible
      therapeutic intervention has been gained. One of most important findings is that
      proteins or molecules influencing apoptosis, inflammation or proliferation of
      vascular smooth muscle cells or endothelial cells, have been found to enhance or
      inhibit neointimal lesion formation in knockout or mutant mice in these models.
      Furthermore, the findings on the origins of endothelial and smooth muscle cells
      in lesions of vein graft and transplant atherosclerosis provided basic
      information that have challenged the traditional hypothesis. Using these models,
      it has also been demonstrated that stem cells identified in blood and bone marrow
      as well as the vasculature contribute to the atherosclerotic lesion formation,
      supporting the importance of murine models of vessel grafts in understanding the
      mechanisms of the vascular diseases. The present review updates the progress of
      the research in this field, by summarizing data of using mouse models of vessel
      grafts, and provides a perspective analysis on the future directions.

PMID- 18336244
TI  - Intimal hyperplasia in murine models.
AB  - The most commonly used procedures to induce arterial injury in mice are carotid
      artery ligation with cessation of blood flow and mechanically-induced denudation
      of endothelium in the carotid or the femoral arteries. Both procedures result in
      neointimal hyperplasia after two to three weeks. A survey of various inbred
      strains of mice shows that strain-specific differences in susceptibility to
      injury-induced neointimal hyperplasia are different than those for susceptibility
      to diet-induced atherosclerosis, with strains identified as susceptible to both
      neointimal hyperplasia and atherosclerosis, resistant to both, susceptible to
      atherosclerosis but resistant to neointimal hyperplasia, or resistant to
      atherosclerosis but susceptible to neointimal hyperplasia. Inflammatory cells
      such as T and B lymphocytes, which are contributory to atherosclerosis, are
      protective against injury-induced neointimal hyperplasia. In contrast, the
      infiltration of monocytes into the site of injury and their differentiation to
      macrophages favor neointimal hyperplasia similar to their pathogenic role in
      atherosclerosis. The regulatory role of lymphocytes and macrophages in neointimal
      hyperplasia is related to the production of cytokines such as interferon-gamma
      and tumor necrosis factor-alpha, respectively. Interestingly, inducible nitric
      oxide synthase (iNOS) activity appears to inhibit neointimal hyperplasia in the
      endothelial denudation model but contributes to neointimal hyperplasia when
      arterial injury is induced by periadventitial cuff placement. The difference
      appears to be due to the time required for endothelial recovery and the
      participation of inflammatory cells. Thus, although arterial injury-induced
      neointimal hyperplasia results in similar vascular occlusion as progressive
      atherosclerosis, the pathology and mechanism of the two disease processes are
      quite different.

PMID- 18336245
TI  - Prospects for the therapeutic application of lentivirus-based gene therapy to HIV
      1 infection.
AB  - Highly active antiretroviral therapy is not sufficient to fully control HIV
      replication and problems of side effects and escape mutation have emerged.
      Current prophylactic and therapeutic vaccine strategies appear to be unable to
      confer full protection. However, given the rapid recent progress made in RNA
      interference and lentivirus technologies, it may soon be possible to develop
      effective gene therapies against HIV infection. We describe here the recent
      progress made in the lentivirus-based HIV-1-targeting RNAi system and the
      possibility that this system can be used to generate an anti-HIV-1 gene therapy.
      We speculate that this system would be most useful if it would be used in a
      coordinated manner with vaccines that can initiate and maintain potent anti-HIV
      immunity.

PMID- 18336246
TI  - Gemini surfactants: a new family of building blocks for non-viral gene delivery
      systems.
AB  - Gemini surfactants provide a significant opportunity in the development of new
      non-viral delivery systems designed for gene therapy applications. This review
      summarizes the wide range of gemini surfactant structures that have been employed
      for DNA transfection in vitro. A general observation is that those structures
      capable of inducing a wide variety of polymorphic structures (lamellar,
      hexagonal, or cubic phases) demonstrate higher transfection efficiencies. Those
      compounds whose structures result in pH-dependent changes in aggregate structure
      similarly show higher levels of transfection. In vivo transfection using gemini
      surfactants has been demonstrated in only three cases, and in a recent study the
      transfection was linked to a specific therapeutic response.

PMID- 18336247
TI  - Gene therapy for rheumatoid arthritis: recent advances.
AB  - The treatment of rheumatoid arthritis (RA) in the last decade has made enormous
      advances with the use of biological therapies. However, these therapies have
      serious limitations such as the expense, side-effects, and the requirement for
      repeated injections, each of which can potentially be obviated by gene therapy. A
      gene therapy approach for the treatment of RA has the potential to stably deliver
      a gene product or multiple products in a target-specific, disease-inducible
      manner. There are many studies investigating gene therapy in RA, the majority of
      which have been designed to test proof-of-principle in an animal model. With an
      abundance of animal studies that have established much promise, the field is now
      at the early stage of moving towards human trials, where patient benefit needs to
      overshadow associated risks, especially since RA is publicly perceived as a non
      life-threatening disease. Here, we provide an overview that focuses on advances
      in the application of gene therapy to RA over the last five years, including:
      novel targets and approaches; the viral and non-viral applications most likely to
      succeed in the clinic; advances in our understanding of the contralateral effect;
      the latest successes with anti-inflammatory cytokines; and a review of
      advancements towards clinical trials.

PMID- 18336248
TI  - Applications of gene therapy to the treatment of chronic pain.
AB  - Chronic pain is a highly prevalent condition that impacts adversely on individual
      quality of life, imposes substantial costs on the healthcare system and a
      considerable burden on society. Advances in the understanding of pain mechanisms
      have opened the way for the development of new treatment strategies. The
      continuous delivery of short-lived potent bioactive molecules to sensory nerves,
      spinal cord or meninges--achieved by directed gene transfer--offers the
      possibility to selectively interrupt nociceptive neurotransmission or to
      interfere with the plastic changes in the nervous system underlying the
      development or persistence of chronic pain. In this review we describe advances
      in the use of non-viral and viral vector-based gene transfer for the treatment of
      pain, with a special focus on the use of recombinant non-replicating herpes
      simplex virus-based vectors and the prospects for clinical trials.

PMID- 18336249
TI  - Potential of gene therapy for restoration of endocrine thymic function in thymus
      deficient animal models.
AB  - The aim of the present article is to discuss the potential of gene therapy for
      thymic hormones as a novel therapeutic strategy to treat dyshomeostatic
      conditions associated with congenital athymia or hypofunction of the endocrine
      thymus. Recent studies using an adenoviral vector harboring a synthetic gene for
      the thymic peptide thymulin are reviewed. This adenoviral vector was injected
      intramuscularly in thymectomized and nude mice as well as in thymectomized rats.
      Transduced myocytes acted as an ectopic source of thymulin thus restoring
      circulating thymulin levels to normal values. This restorative effect was long
      lasting (several months) even though an adenoviral vector was used. In the rat
      brain, adenovirally-mediated delivery of the synthetic gene for thymulin achieved
      longer expression than in the case of adenovirally-delivered reporter genes,
      which is consistent with the reported antiinflammatory activity of thymulin in
      the brain. Furthermore, neonatal thymulin gene therapy in nude female mice was
      able to prevent the pituitary and ovarian alterations that typically occur in
      this mutant after puberty. Neonatal thymulin gene therapy in nude mice was able
      to prevent some of the alterations in lipid metabolism that develop during adult
      life in congenitally athymic mice. We conclude that the availability of the above
      biotechnological tools should boost basic studies on the molecular biology of
      thymulin and should also allow an assessment of the potential of gene therapy to
      restore circulating thymulin levels in thymodeficient animal models and
      eventually, in humans.

PMID- 18336250
TI  - Baculoviral vectors for gene delivery: a review.
AB  - Baculovirus has emerged as a novel vector for in vivo and in vitro gene delivery.
      In addition, the applications of baculovirus-mediated gene transfer have been
      explosively expanded to drug screening, eucaryotic gene display, cancer therapy
      and tissue engineering, etc. The capability of baculovirus viral envelope for
      protein/peptide display also renders itself a potential vaccine delivery
      platform. This paper reviews the history, factors influencing baculovirus
      mediated gene delivery and emerging in vitro, in vivo and ex vivo applications.
      Efforts aimed at overcoming current existing bottlenecks and recent progresses in
      addressing the safety concerns are particularly emphasized.

PMID- 18336251
TI  - Immunomodulation via targeted inhibition of antigen receptor signal transduction.
AB  - Coronary artery vasculopathy (CAV), characterized by diffuse concentric coronary
      artery intimal thickening with fibrosis, remains a significant complication
      impeding long term engraftment in heart transplantation. The pathophysiologic
      processes driving CAV are not well understood, however T cell mediated cellular
      immunity and cytokines have been implicated. The inability to prevent CAV may be
      related in part to a limited spectrum of inhibition that that current
      immunosuppressive therapies exhibit against second messenger pathways elicited by
      T cell receptor (TCR) activation and dose limiting toxicities. Therefore,
      considering that antigen specific T cell activation is initiated at the TCR,
      including alloresponses involving direct and indirect antigen presentation,
      targeting the proximal kinases involved in this process may provide novel
      therapeutic options for controlling rejection. Src family kinases (SFK),
      particularly p56(lck) (Lck) and p59(fyn) (Fyn), are intimately associated with
      the earliest signaling events through the TCR and could provide targets for
      immunomodulatory agents. Such targeted inhibition of TCR signaling may institute
      a novel approach for diminishing the T cell mediated response associated with
      CAV. In this review we discuss therapeutic agents that have been shown to inhibit
      SFK and the rationale for investigating the potential application of these agents
      in heart transplantation.

PMID- 18336252
TI  - Adiponectin and its role in cardiovascular diseases.
AB  - Studies performed during the last decade indicate that adipose tissue is not only
      a site of triglyceride storage but also an active endocrine organ which secretes
      many biologically active mediators referred to as "adipokines". In contrast to
      many adipokines which are overproduced in obese individuals and exert deleterious
      effects on insulin sensitivity, lipoprotein metabolism and cardiovascular system,
      such as leptin, tumor necrosis factor-alpha, plasminogen activator inhibitor-1,
      resistin, etc., adiponectin seems to be a unique adipokine which is produced in
      lower amounts in obese than in lean subjects and possesses predominantly
      beneficial activities, i.e. increases insulin sensitivity, stimulates fatty acid
      oxidation, inhibits inflammatory reaction and induces endothelium-dependent
      nitric oxide-mediated vasorelaxation. Adiponectin binds two receptors, AdipoR1
      and AdipoR2. Adiponectin knockout mice exhibit various manifestations of the
      metabolic syndrome such as insulin resistance, glucose intolerance,
      hyperlipidemia, impaired endothelium-dependent vasorelaxation and hypertension,
      as well as augmented neointima formation after vascular injury. Clinical studies
      indicate that plasma adiponectin concentration is lower in patients with
      essential hypertension and ischemic heart disease. Raising endogenous adiponectin
      level or increasing the sensitivity to this hormone may be a promising
      therapeutic strategy for patients with metabolic and cardiovascular diseases.
      Among currently used drugs, thiazolidinediones (peroxisome proliferator activated
      receptor gamma agonists) are most effective in elevating adiponectin level.

PMID- 18336253
TI  - Reduction of myocardial ischemia-reperfusion injury with pre- and
      postconditioning: molecular mechanisms and therapeutic targets.
AB  - Reduction of infarct size as well as alleviation of other ischemia- and
      reperfusion-associated injuries are the goals of primary importance in
      cardiology. One of the remedies is considered to be myocardial preconditioning
      (PreCon) referred usually to as an increased myocardial tolerance to prolonged
      ischemia following brief ischemic or non-ischemic challenge. In this review,
      PreCon stimuli tested to date are considered including a number of mildly noxious
      factors applied either locally to the myocardium or systemically. Recently, one
      more mode of heart protection against reperfusion injury termed postconditioning
      (PostCon) has been developed. On the basis of ample evidence published, along
      with our findings, a detailed comparative analysis of PreCon and PostCon is
      presented, with special emphasis on the cellular, molecular, and pharmacological
      aspects of the topic as well as clinical applications, both implemented and
      awaiting practical approval.

PMID- 18336254
TI  - Receptor subtype abundance as a tool for effective intracellular signalling.
AB  - The regulation of heart function is one of the essentials for the survival of
      organism. Therefore, the effective mechanisms of regulation can minimize the
      energy requirements and improve the ability to react to different needs on time
      and appropriately. Two receptor types, beta-adrenoceptors and muscarinic
      receptors, with almost antagonistic function, are "basic regulators" of the heart
      parameters. It is relevant to mention that beside the main adrenoceptors and
      muscarinic receptors subtypes (beta(1)- and M(2)-subtype), other minor subtypes
      that regulate heart function, i.e. beta-, beta-adrenoceptors, alpha(1)
      adrenoceptors and minor subtypes of muscarinic receptors (M(1), M(3) and M(5))
      are present in the heart. In this regard is intriguing that just two
      catecholamines (adrenaline, noradrenaline) have many "targets"--receptors that
      differ so much in the functional consequences of their activation: while beta(1)-
      and beta(2)-adrenoceptors cause cardiostimulation, beta(3)-adrenoceptors are
      responsible for cardioinhibition and alpha(1)-adrenoceptors contribute to
      enhanced inotropy. Similarly, some data show that other muscarinic receptors than
      M(2) muscarinic subtype, are expressed in the heart and these minor subtype(s)
      can contribute to the heart regulation in similar way as beta(3)-adrenoceptors to
      the catecholamine action. Taken together, regulation of heart function through
      different receptor subtypes and using homologous and heterologous regulation can
      represent an effective tool for coping with permanently changing environmental
      conditions.

PMID- 18336255
TI  - Mast cells and inflammatory heart disease: potential drug targets.
AB  - Inflammation underlies the pathogenesis of many common cardiovascular diseases
      (CVD) such as myocardial infarction, atherosclerosis, myocarditis and dilated
      cardiomyopathy. Allergic disorders like allergic rhinitis and asthma, both
      chronic inflammatory conditions, have recently been linked to increased CVD and
      death. Studies have found that increased IgE levels, eosinophilia, positive skin
      prick tests, self-reported asthma and enzymes that regulate leukotriene synthesis
      (5-lipoxygenase) predict a high risk for atherosclerosis, stroke and myocardial
      infarction. Mast cells (MCs), cells involved in the pathogenesis of allergy and
      asthma, are emerging as key players in the regulation of inflammation and
      fibrosis in the heart and vasculature. Our laboratory has found that MC numbers
      are increased in mice susceptible to developing chronic dilated cardiomyopathy.
      The fibrosis associated with chronic heart disease is increased by MC
      degranulation. MCs can also act as antigen-presenting cells increasing
      inflammation in the heart through Toll-like receptor-4 signaling and increased
      proinflammatory cytokine production. Similar inflammatory mechanisms are observed
      for myocarditis and atherosclerosis. Many of the drugs currently used to reduce
      heart disease act on mediators/ pathways downstream of MC degranulation. An
      improved understanding of the role of MCs in regulating inflammation and fibrosis
      will enable researchers and clinicians to better treat heart disease.

PMID- 18336256
TI  - Advances in the structural understanding of Vif proteins.
AB  - The multidomain HIV-1 Vif protein recruits several cellular partners to achieve
      neutralization of the antiviral activity of APOBEC3 proteins. Vif neutralizes
      APOBEC3G and APOBEC3F predominantly by forming an E3 ubiquitin ligase with
      Cullin5, ElonginB and ElonginC that targets these proteins for degradation by the
      ubiquitin-proteasome pathway. Vif associates with the Cullin5-ElonginB-ElonginC
      complex by binding directly to ElonginC via its SOCS-box motif and to Cullin5 via
      hydrophobic residues within a zinc-binding region formed by a conserved HCCH
      motif. The HIV-1 Vif-Cullin5-ElonginBC complex is then able to ubiquitinate the
      APOBEC3G factor bound to Vif by its N-terminal domain. In this review, we
      summarize the current knowledge about the structural determinants of Vif that
      allow it to interact with cellular and viral partners.

PMID- 18336257
TI  - Patients' characteristics and clinical implications of suboptimal CD4 T-cell
      gains after 1 year of successful antiretroviral therapy.
AB  - To describe characteristics and prognosis of patients with suboptimal
      immunological response to combined antiretroviral therapy (CART). Using data from
      a multicenter cohort study, we selected patients who initiated CART and showed
      suboptimal CD4-T cell response (defined as <50 cells/L increase) after 1 year of
      therapy, despite sustained virological suppression. Characteristics of those
      patients were compared with subjects who showed optimal immunological response.
      Of 650 patients with virological suppression, 108 (16.6%) showed suboptimal CD4-T
      cell response. Independent predictors of suboptimal response were previous
      injection drug use (OR, 1.85; 95% CI, 1.12-2.98) and age at CART initiation (OR,
      1.04 per year increase; 95%CI, 1.01-1.06). Hepatitis C virus coinfection was not
      associated with impaired immunological response. As compared with patients with
      optimal immunological response, those with suboptimal response had a higher
      mortality rate (3.22 versus 0.71 per 100 person-years; p=.001), but a similar
      rate of new AIDS-defining events. In patients with sustained virological
      suppression with CART, previous injection drug use, but not hepatitis C virus
      coinfection, and older age at initiation of therapy were associated with
      suboptimal CD4 T-cell responses. Patients with suboptimal response had a higher
      mortality over time, mainly due to diseases other than AIDS-defining events.

PMID- 18336258
TI  - Continuous crossover(s) events of HIV-1 CRF01_AE and B subtype strains in
      Malaysia: evidence of rapid and extensive HIV-1 evolution in the region.
AB  - The Asian HIV epidemic appears to be complex, characterized by the prevalence of
      multiple subtypes and circulating recombinant forms with gradual replacement of
      pure HIV-1 subtypes in several geographical regions. The main objectives of the
      present study are to identify and analyse the full-length viral genomes of three
      unique recombinant forms (URFs); the HIV-1 isolates 07MYKLD47, 07MYKLD48 and
      07MYKLD49 from Malaysia. Long-range polymerase chain reaction (PCR) amplification
      of seven overlapping reading frames was used to derive near full-length HIV-1
      genomes. Detailed phylogenetic and bootscanning analyses were performed to
      determine phylogenetic associations and subtypic assignments. We further
      confirmed the mosaic composition of these CRF01_AE/B inter-subtype recombinant
      forms, which are composed of B-subtype fragment(s) in the backbone of CRF01_AE.
      Both 07MYKLD47 and 07MYKLD48 have an insertion of B subtype (880 bp and 532 bp)
      in the gag-pol and gp41-env gene regions, respectively. Whereas the isolate
      07MYKLD49 has three B-subtype fragments inserted in different gene region along
      the genome; one each in the gag-pol (1862 bp) and pol-vif (1935 bp) regions, and
      a short B-subtype insertion (541 bp) in the 5' LTR-gag region. This highlights
      the public health relevance of newly emerging second generation HIV-1 recombinant
      forms and their dispersal, along with their rapid and continuous evolution in the
      region.

PMID- 18336259
TI  - Nef and TNFalpha are coplayers that favor HIV-1 replication in monocytic cells
      and primary macrophages.
AB  - The human immunodeficiency virus (HIV) Nef protein is myristoylated and plays a
      critical role in AIDS pathogenesis by enhancing viral replication, survival of
      the virus within infected cells and by facilitating its spread in vivo. We
      observed that, in the promonocytic cell line U937, myristoylated exogenous Nef
      protein activates NF-kappaB and AP-1, whereas unmyristoylated exogenous Nef
      protein does not. Using methyl-beta-cyclodextrin (MbetaC) treatment, we observed
      that the activation of NF-kappaB and AP-1 by exogenous Nef protein is mediated
      primarily via lipid rafts both in U937 cells and in primary human macrophages. In
      agreement with this observation, exogenous Nef protein colocalized with GM1
      ganglioside, a major component of lipid rafts, in U937 cells as detected by
      confocal microscopy. Since tumor necrosis factor alpha (TNFalpha) activates NF
      kappaB and AP-1, we investigated the role of exogenous Nef protein in TNFalpha
      stimulated U937 cells and primary macrophages. We observed that exogenous Nef and
      TNFalpha synergistically activate NF-kappaB and AP-1 in U937 cells and primary
      macrophages resulting in enhanced stimulation of the HIV-1 long terminal repeat
      (LTR), and subsequently in enhanced viral replication in both chronically
      infected promonocytic U1 cells and acutely HIV-1-infected primary macrophages.
      Both enhanced LTR stimulation and viral replication following treatment with
      exogenous Nef and TNFalpha were mediated via lipid rafts. Therefore, our results
      indicate that exogenous Nef protein and enhanced TNFalpha production detected in
      HIV-infected subjects could synergize to fuel the progression of the disease via
      lipid raft-dependent stimulation of the HIV-1 provirus present in such cellular
      reservoirs as mononuclear phagocytes.

PMID- 18336260
TI  - Impact of residues in the nonnucleoside reverse transcriptase inhibitor binding
      pocket on HIV-1 reverse transcriptase heterodimer stability.
AB  - Previous studies have demonstrated that nonnucleoside reverse transcriptase (RT)
      inhibitors (NNRTIs) act as chemical enhancers of human immunodeficiency virus
      type 1 (HIV-1) RT dimerization. In the current study, we sought to define the
      role of key residues (101, 103, 108, 181, 188, 190, 225 and 318) in the NNRTI
      binding pocket on HIV-1 RT heterodimer stability. Thirteen mutant RTs were
      constructed and evaluated for p66/p51 RT heterodimer formation using the well
      established yeast two-hybrid assay. We found that the mutations K101A, P225H,
      Y318F and Y318W decreased RT heterodimer stability whereas K103N, V108I, V108W,
      Y181C, Y188L, G190A, G190E, G190W and P225W increased RT heterodimer stability.
      While these results demonstrate that residues that comprise the NNRTI-binding
      pocket contribute to the stability of p66/p51 HIV-1 RT, they did not suggest any
      obvious correlation between RT dimer stability and the extent of NNRTI
      resistance. Remarkably, mutations at residue G190 (A, E, W) in the p66 RT subunit
      were found to dramatically increase heterodimer stability. Notably, the G190W
      mutation increased RT dimer stability almost to the same extent as did 5 microM
      efavirenz. In light of these findings, we characterized the in vitro activity of
      recombinant RT expressing mutations at G190 in the p66 subunit only and compared
      them with a wild-type enzyme complexed with efavirenz. We found that while
      mutations at G190 had a significant effect on both the DNA polymerase and
      ribonuclease H activity of the enzyme, their phenotypic effects did not mirror
      those induced by efavirenz-binding to RT.

PMID- 18336261
TI  - Relationship between HIV-RNA load in blood and semen in antiretroviral-naive and
      experienced men and effect of asymptomatic sexually transmissible infections.
AB  - We assessed the correlation between HIV-RNA viral load in blood (BPVL) and
      seminal plasma (SPVL) in a cross-sectional cohort of 119 asymptomatic,
      antiretroviral-naive and experienced HIV-1 subjects (BPVL < 50 copies/mL for
      minimum 12 months and stable on one drug regimen). The cohort was divided into 3
      groups: 2 according to the non nucleoside reverse transcriptase inhibitor (NNRTI)
      and protease inhibitor (PI) used, and 1 untreated group. At the initial visit,
      subjects were screened for gonorrhoea, chlamydia and syphilis. Blood was
      collected for CD4 count, BPVL, and general biochemistry and haematology. Semen
      was collected concurrently and SPVL determined by the NucliSens HIV-1 QT PCR
      (BioMerieux, Boxtel, The Netherlands). At a subsequent visit, a second semen
      sample was obtained and SPVL was repeated for 10 subjects on ART. All NNRTI
      subjects (n = 36, mean treatment 33 months +/- 14) and PI subjects (n = 45, mean
      treatment 31 months +/- 25) had BPVL < 50 copies/mL and SPVL < 250 copies/mL at
      baseline and with repeat sampling. 9/119 subjects (8%) had an asymptomatic STI; 4
      cases in the treated groups and 5 in the untreated group. Treated subjects were
      less likely to have an STI than untreated subjects. In conclusion, asymptomatic
      STIs had no effect on BPVL or SPVL in either treated group and SPVL remains
      undetectable over time. STIs minimally increase, or do not increase, SPVL in
      untreated patients. Our data supports the role of ART in lowering the risk of
      sexual transmission of HIV-1.

PMID- 18336262
TI  - A re-look at recent statistics on mortality in the context of HIV/AIDS with
      particular reference to South Africa.
AB  - Since the outbreak of the HIV epidemic in the 1980s, various organisations and
      researchers have produced statistics on HIV/AIDS including HIV prevalence,
      incidence, number of AIDS cases, AIDS-related mortality as well as life
      expectancy at birth in the context of HIV/AIDS. Until recently HIV-prevalence
      statistics as well as models projecting the impact of HIV/AIDS utilised HIV
      prevalence statistics based on women attending antenatal clinics as population
      based prevalence statistics were non-existent. Among others, the extrapolation of
      HIV-prevalence statistics from surveillance sites to the general population has
      been questioned. Recent statistics on HIV-prevalence from population-based
      surveys strongly suggest that HIV-prevalence in many countries may not be as high
      as earlier estimated and projected. In addition, model estimates of HIV/AIDS
      prevalence and impact on mortality often use conventional model life tables such
      as the Coale-Demeny Regional, UN, and Brass standard life tables, which in the
      case of South Africa give female life expectancy at birth plummeting from about
      65 years in the mid-1990s to around 49-50 years in 2005. The standard life tables
      often employed in these estimates do not take account of the 'hump' in the
      mortality curve due to AIDS-related deaths as these standard mortality schedules
      were developed prior to the HIV/AIDS epidemic. Given this background, this paper
      provides a critical look at recent statistics on infant mortality rates and life
      expectancies at birth in the context of HIV/AIDS in parts of Southern and Eastern
      Africa with particular reference to South Africa.

PMID- 18336263
TI  - Photopheresis in HIV-1 infected patients utilizing benzoporphyrin derivative
      (BPD) verteporfin and light.
AB  - An ex vivo trial utilizing photopheresis with Benzoporphyrin Derivative as the
      photoactive compound, identified the minimum energy levels of light and
      concentrations of BPD that eradicated both cell-free and cell-associated HIV-1
      infectivity without destroying the virus particles or infected leukocytes.
      Leukocytes remained viable with altered chemokine/cytokine expression. Apoptosis
      was induced in a minority of CD4 but not CD8 positive cells with a statistically
      significant increase in cytolytic T-cell activity. In the 24 week clinical trial
      in 7 HIV-1 infected patients, three who had rapidly rising viral loads prior to
      initiating therapy stabilized. Two had a sustained greater than 0.5 log decrement
      and 5 had stable plasma viral loads (less than a 0.5 log increment or decrement)
      with varied effects on absolute CD4 and CD8 positive lymphocytes counts. One
      achieved a greater than 1 log decrement in HIV-1 plasma viral load and
      undetectable in vivo cell-free and cell-associated HIV-1 infectivity with an
      increased in vitro lymphocyte mitogen stimulation index. Under amended protocol,
      5 additional 12 month courses were administered to three additional patients and
      two of the previous enrollees. Area under the curve for viral load showed a
      significant decrease from pre- to post-therapy (p 0.007). No associated
      toxicities were observed.

PMID- 18336264
TI  - Adherence to highly active antiretroviral therapy in HIV-infected inmates.
AB  - Adherence to highly active antiretroviral therapy (HAART) has been scarcely
      studied in correctional settings. Our study aims to evaluate the relationship
      between adherence and virological outcome and to determine factors related to
      adherence in correctional settings. A cross-sectional retrospective study was
      performed in Topas prison (Salamanca, Spain). 50 inmates starting HAART were
      studied. Adherence was estimated through a self-report questionnaire and
      variables related to adherence (covering individual factors, the illness itself
      and the therapeutic regimen) were recorded. HIV-RNA levels and CD4 lymphocyte
      count were measured before starting therapy and six months after. Statistical
      analysis was performed using univariate and multivariate methods. 21 inmates
      (42%) were considered adherent and 29 (58%) were non-adherent. Adherence to
      treatment, as measured by our questionnaire, was the only significant and
      independent factor associated with an undetectable viral load at six months of
      therapy. Five variables were significantly associated with adherence to
      treatment, four of them as predictor factors for good adherence: an active
      occupation inside prison, the absence of HIV-related symptoms, a good or average
      acceptance of treatment, and a higher academic background; previous injection
      drug use as a risk factor for HIV transmission was associated with non-adherence.
      A simple self-report questionnaire may be useful for assessing adherence in
      prison inmates. Recognizing variables associated with adherence is essential to
      identify prisoners at high risk of being non-adherents in order to develop
      strategies for improving compliance.

PMID- 18336265
TI  - Antiretroviral therapy voluntarily taken at half-dosage, but fully effective
      after 6-10 years: a provocative issue for adherence requirements: case report.
AB  - Aim of our report is to discuss some key adherence features in the real world, by
      reporting two exceptional patients, who deliberately took all antiretroviral
      medications at half-dosage compared with standard prescriptions, and maintained a
      fully stable and sustained virological and immunological response after 6-10
      consecutive years. The potential causes and consequences of this apparent
      misconduct of our patients on drug tolerability, resistance development,
      compliance monitoring, direct drug delivery, and health care providers behavior,
      are discussed.

PMID- 18336266
TI  - Impact of occult HBV infection in HIV/HCV co-infected patients: HBV-DNA detection
      in liver specimens and in serum samples.
AB  - Prevalence and impact of occult HBV infection in HIV positive patients is
      controversial. The aims of this study were to determine the prevalence of occult
      HBV infection and its impact on histological and virological parameters. 52
      HIV/HCV (but HBsAg-negative) co-infected patients, 29 HBsAg and anti-HCV negative
      chronic hepatitis, and 20 HBsAg positive chronic hepatitis controls were studied.
      DNA was extracted from frozen biopsies and amplified with primers for S, C and X
      regions, and for (ccc) HBV-DNA. Sera were tested for HBV-DNA with two
      quantitative assays (Cobas Amplicor HBV Monitor, and the real-time COBAS (r)
      Taqman HBV Test, Roche Diagnostics, UK). Occult HBV infection was detected in 7
      (13.4%) liver biopsies of the study group, and in none case of the non viral
      chronic hepatitis group (p=0.04). All serum samples were HBV-DNA negative with
      Cobas Amplicor HBV monitor assay, while 3 cases were found positive with real
      time PCR. Statistical analysis didn't show any impact of occult HBV infection on
      liver histology, CD4+ cells count, HIV and HCV load, and ALT levels. Occult B
      infection is relatively frequent in HIV/HCV co-infected patients, and is
      underestimated by common HBV-DNA serological assays. However, it doesn't seem to
      exert a relevant impact.

PMID- 18336267
TI  - Preclinical and clinical studies of novel breast cancer drugs targeting molecules
      involved in protein kinase C signaling, the putative metastasis-suppressor gene
      Cap43 and the Y-box binding protein-1.
AB  - Breast cancer is a common cause of tumors in women. The development of effective
      adjuvant therapies using drugs such as anthracyclines, taxanes, and aromatase
      inhibitors has improved the survival of breast cancer patients. Molecular cancer
      therapeutics are also attracting attention, and targeted molecular therapies,
      such as trastuzumab, have already contributed to effective new treatments for
      breast cancer. Other candidate targeted molecular therapies for breast cancer,
      including erlotinib, gefitinib, lapatinib, bevacizumab, and celecoxib, are
      currently undergoing clinical evaluation, and promising results are expected. The
      current review provides an up-to-date summary of the preclinical and clinical
      development of these drugs for breast cancer. In particular, we focus on
      therapies targeting protein kinase C (PKC) signaling, the putative metastasis
      suppressor gene Cap43/N-myc downstream-regulated gene 1 (NDRG1)/differentiation
      related gene-1 (Drg-1), and the Y-box binding protein-1 (YB-1). The PKC signaling
      pathway is widely considered to be a promising target for the development of
      novel therapeutics. Cap43 expression is significantly modulated by estrogen
      and/or anti-estrogens in breast cancer cells that are positive for estrogen
      receptor-alpha (ER-alpha). Cap43 is therefore of particular interest as a
      molecular indicator of the therapeutic efficacy of anti-estrogenic agents in
      breast cancer. The nuclear expression of YB-1 plays an essential role in the
      acquisition of malignant characteristics by breast cancer cells, through
      epidermal growth factor receptor 2 (HER2)-Akt-dependent pathways. Basic research
      investigating the key selective molecular changes that sustain breast cancer
      growth and progression, as demonstrated for PKC, Cap43, and YB-1, is allowing the
      development of specific targeted molecular diagnostics and therapeutics.

PMID- 18336268
TI  - MAPKs as mediators of cell fate determination: an approach to neurodegenerative
      diseases.
AB  - Neurodegenerative diseases do affect glial or neuronal cells in both the
      peripheral and central nervous systems. Although they are characterized by
      different features and a different onset, all the neurodegenerative diseases
      share the final steps that lead to cell death by apoptosis. Apoptosis occurs also
      during developmental neurogenesis. Neuron survival and differentiation depend on
      specific neurotrophic factors released by their targets. During degenerative
      diseases the loss of neuronal or glial cells is responsible for the disease's
      progression. Current therapies are focused on counteracting the degenerative
      events by acting on the molecular mechanisms involved in cellular death, or by
      the exogenous administration of pro-survival factors. The presence in many areas
      of both the peripheral and central nervous systems of niches of neural
      progenitors which can differentiate, under specific conditions, into neurons or
      glial cells opens up new therapeutic perspectives. The Mitogen-Activated Protein
      Kinase (MAPK) family, that includes ERK1/2, JNK/SAPK, p38 and ERK5, is involved
      in the survival, proliferation and differentiation of nervous cells. Some of the
      MAPKs promote the differentiation towards the neuron lineage, others towards the
      glial one. The MAPKs are also involved in apoptosis and may, therefore, play a
      role in neurodegeneration. This dual role of MAPKs may make it possible to design
      alternative and/or synergistic approaches to the treatment of degenerative
      diseases, either by using specific inhibitors of the MAPKs involved in apoptosis,
      or by increasing the activation of the MAPKs involved in neuronal survival and
      differentiation. The increased activation of pro-differentiative MAPKs can lead
      to the replacement of damaged neurons by undifferentiated progenitors and the
      slowing down of the disease's progression.

PMID- 18336269
TI  - Adaptor protein 3BP2 and cherubism.
AB  - The adaptor protein 3BP2 (c-Abl Src homology 3 domain-binding protein-2, also
      referred to SH3BP2) is known to play a regulatory role in signaling from
      immunoreceptors. In mast cells, 3BP2 is rapidly tyrosine phosphorylated by the
      aggregation of the high affinity IgE receptor and the overexpression of its SH2
      domain results in the dramatic suppression of IgE-mediated tyrosine
      phosphorylation of PLC-alpha, Ca2+ mobilization and degranulation. 3BP2 is a
      substrate of the protein-tyrosine kinase Syk, which phosphorylates it on Tyr174,
      Tyr183, and Tyr446 (in the mouse protein). Phosphorylation of Tyr183 promotes the
      activation of Rac1 through the interaction with the SH2 domain of Vav1.
      Phosphorylation of Tyr446 induces the binding to the SH2 domain of the upstream
      protein-tyrosine kinase Lyn and enhances its kinase activity. Thus, 3BP2 has a
      positive regulatory role in IgE-mediated mast cell activation. In lymphocytes,
      engagement of T cell or B cell receptors triggers tyrosine phosphorylation of
      3BP2. Suppression of the 3BP2 expression by siRNA results in the inhibition of T
      cell or B cell receptor-mediated activation of NFAT. Genetic analyses reveal that
      3BP2 is required for the proliferation of B cells and B cell receptor signaling.
      Point mutations of the 3BP2 gene cause the rare human inherited disorder
      cherubism, characterized by excessive bone resorption in the jaw bones. These
      mutations include substitution and deletion mutations of 3BP2. "Cherubism" mice
      exhibit increased myeloid cell responses to M-CSF and RANKL leading to the
      activation of osteoclasts. Further analysis could demonstrate that inhibition of
      3BP2 might have therapeutic potential.

PMID- 18336270
TI  - Proteomics and cardiovascular disease: an update.
AB  - Proteomics has unraveled important questions in the biology of cardiovascular
      disease and holds even greater promise for the development of novel diagnostic
      and prognostic biomarkers. This approach may establish early detection
      strategies, and monitor responses to therapies. Technological advances (most
      notably blue native polyacrylamide gel electrophoresis, electrospray ionization,
      matrix-assisted laser desorption/ionization (MALDI), analysis of MALDI-derived
      peptides in Time-of-Flight (TOF) analyzers, and multidimensional protein
      identification technology (MudPIT) and bioinformatics for data handling and
      interpretation allow a large-scale identification of peptide sequence and post
      translational modifications. Moreover, combination of proteomic biomarkers with
      clinical phenotype, metabolite changes, and genetic haplotype information is
      promising for the physician assessment of individual cardiovascular risk profile.

PMID- 18336271
TI  - Synthetic small molecule Cdc25 phosphatases inhibitors.
AB  - Inhibition of Cdc25 phosphatases is a strategy for the discovery and development
      of novel anticancer agents targeting the cell cycle. A number of potent small
      molecule Cdc25 inhibitors have been identified. They are derived from different
      chemical classes; the most potent and selective derivatives are quinones. The
      electrophilic properties of quinones suggest the possibility of inducing a
      sulphydryl arylation of a cysteine in the enzyme active site. It is also possible
      that inhibition is due to redox cycling activity and production of ROS. Thus,
      oxidation of the thiolate form of cysteine occurs, leading to inactivation of
      enzymatic activity. Many of these inhibitors are active on all three Cdc25
      phosphatases, cause cell cycle arrest and inhibit the growth of several human
      tumor cell lines. The possibility of toxicities induced by ROS, prompted the
      search for non-quinoid antagonists. It is not yet clear how these compounds bind
      within the enzyme's active site. Generally, electrophilic moieties able to trap
      the catalytic cysteine play an important role. Another strategy for identifying
      Cdc25 inhibitors is the development of compounds able to interact with the
      conserved loop region instead of phosphate.. In this review a summary of the most
      interesting Cdc25 inhibitors is given together with their biological activity.
      SAR studies concerning the importance of some structural features will be
      described.

PMID- 18336272
TI  - Inflammatory markers in SIRS, sepsis and septic shock.
AB  - Despite great advancement in the understanding of the pathophysiology and in the
      development of novel therapeutic approaches, mortality of sepsis still remains
      unacceptably high. Adequate laboratory diagnostics represents a major requirement
      for the improvement of this situation. For a better understanding of the
      immunological dysregulation in this disease, several markers are now available
      for routine diagnostics in the clinical laboratory. They include the cytokines
      interleukin (IL) -6, IL-8, procalcitonin and the LPS-binding protein (LBP). These
      novel markers will be compared to the conventional procedure of diagnosing
      inflammatory and infectious disease, such as measurements of C-reactive protein
      (CRP) as a major acute phase protein and differential blood counting. Important
      questions addressed in this review are the usefulness of these markers for early
      diagnosis, their role as prognostic markers and in the risk assessment of
      patients. Furthermore, we will discuss whether these parameters are to
      differentiate between systemic inflammatory response syndrome (SIRS) and sepsis
      at its different degrees. In the case of an infectious nature of the disease, it
      is important to differentiate between viral or bacterial origin and to monitor
      the responsiveness of antibiotic therapies. The literature was analysed with
      focus on the evidence for diagnostic and analytical performance. For this purpose
      international definition and staging criteria were used in context of criteria
      for assay performance including sensitivity, specificity, negative and positive
      predictive values, ROC analysis and other analytical criteria.

PMID- 18336273
TI  - Pulmonary coagulopathy as a new target in lung injury--a review of available pre
      clinical models.
AB  - Despite recent advances in supportive care, acute lung injury (ALI) and its more
      severe form acute respiratory distress syndrome (ARDS) are clinical entities with
      high morbidity and high mortality. In systemic inflammation, like sepsis,
      uncontrolled host defense can lead to systemic activation of coagulation on the
      one hand, and attenuation of fibrinolysis on the other. In ALI/ARDS similar but
      local disturbances in fibrin turnover occur, leading to excessive alveolar fibrin
      deposition compromising pulmonary integrity and function. Therapies in patients
      with sepsis have specifically focused on coagulation disturbances. Evidence from
      preclinical and clinical investigations suggests pharmacologically targeting
      pulmonary "coagulopathy" could be of benefit to patients with ALI/ARDS as well.
      Recent animal studies have demonstrated that administration of heparins,
      activated protein C (APC), Antithrombin (AT), Tissue factor-Factor VIIa (TF
      FVIIa) pathway inhibitors, plasminogen activators (PA) and thrombomodulin (TM)
      can attenuate pulmonary coagulopathy and reduce lung injury and/or improve
      oxygenation. Some of these studies have also shown anti-inflammatory effects of
      treatment targeting at coagulation. To date there are no published studies that
      have specifically studied the effects of anticoagulants on ALI/ARDS however there
      are on-going clinical trials. A solid base has to be provided by preclinical
      studies to justify clinical studies on new pharmacologic therapies for ALI/ARDS.
      In this systematic literature review we give an overview of the models for
      ALI/ARDS that have been used so far on the topic of pulmonary coagulopathy and
      focus on the pharmacological interventions that have been evaluated with these
      models. Finally, the applicability of the different approaches for future
      research on this subject will be discussed.

PMID- 18336274
TI  - Flow cytometry study of leukocyte function: analytical comparison of methods and
      their applicability to clinical research.
AB  - Perturbations in the redox-based network of cellular regulatory mechanisms have
      been associated with oxidative-related diseases such as diabetes mellitus. In
      these situations the redox state of cellular redox systems becomes persistently
      shifted toward oxidation that may result in a sequence of pathophysiological
      events. Innate and adaptive immune responses depend on the production of reactive
      oxygen species and ATP synthesis, which are tightly regulated by the
      mitochondrial transmembrane potential. Mitochondrial hyperpolarisation is a key
      mechanism of T-cell life, apoptosis and autoimmunity. The NADPH oxidase of the
      phagocytic cells of the immune system generates reactive oxygen metabolites
      during the respiratory burst, but activated B cells also possess NADPH oxidase
      and reactive oxidants could play regulatory roles in immune function. Cellular
      thiol levels and the thiol reduction-oxidation process modulate the oxidative
      metabolism in the cells, transcriptional factor activation of gene expression,
      lymphocyte proliferation and death. Flow cytometry allows directly characterising
      and analysing several parameters and functions of intact living cells in a few
      seconds. Fluorescent lipophilic cations have been used for the measurement of the
      mitochondrial transmembrane potential. Evaluation of reactive oxygen
      intermediates generation in neutrophils may be obtained by use of oxidation
      sensitive probes. The dye resazurin has been used to quantify mitochondrial
      activity since considered to act as an intermediate electron acceptor in the
      electron transport chain between the final reduction of oxygen and cytochrome
      oxidase. The fluorescence emitted by 5-chloromethyl fluorescein acetate stained
      cells reflects the total level of free intracellular thiol. In this review we
      will discuss the possible importance and consequences of evaluating these redox
      parameters in diabetes pathophysiology. Moreover, we will provide perspectives
      concerning the varieties of analytical procedures that are capable of measuring
      them. The advantages and disadvantages of each of these methods are critically
      discussed particularly in view of their clinical application.

PMID- 18336275
TI  - Granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation
      and its clinical usefulness.
AB  - In 1980, Espey proposed a famous hypothesis that mammalian ovulation is
      comparable to an inflammatory reaction and many researches have proved the
      validity of his hypothesis in the last three decades. For example, interleukin
      (IL)-1beta, IL-6, tumor necrosis factor (TNF)- alpha, granulocyte-macrophage
      colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF)
      and other inflammatory cytokines presence was proven in the preovulatory
      follicle. Since granulocyte is the major leukocyte and it plays a very important
      role during inflammation, the importance of granulocyte and its related cytokine,
      granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation
      is easily predictable. G-CSF is one of the hemopoietic cytokines and it has
      strong positive effects on granulocytes. G-CSF increases the number of
      granulocytes and it improves the function of granulocytes. In this review, the
      participation of leukocytes in the ovulation mechanism is demonstrated first.
      Second, the participation of G-CSF is shown in comparison with the above
      mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as
      a medicine without severe side effects in the field of oncology, the clinical
      application of G-CSF for the treatment of an ovulation disorder, luteinized
      unruptured follicle (LUF), will be discussed.

PMID- 18336276
TI  - Potential biochemical events associated with initiation of labor.
AB  - Much of our understanding and knowledge of human parturition has been blurred by
      conjecture and extrapolation. The limited available data on human parturition
      reflect the inability to directly experiment with pregnant human subjects. In
      spite of this obvious impediment and the scarcity of longitudinal data on
      fundamental physiological changes in human pregnancy, recent reports have
      generated a better understanding of the synchronous activities leading to labor.
      The purpose of this review was to organize, in an evidence-based format, the
      current understanding of maternal physiologic phenomena leading from uterine
      quiescence to uterine labor activity. Recent discoveries have prompted a revision
      of pre-existing classical theories on the initiation of parturition, such as the
      progesterone block theory or the prostaglandins stimulation of the uterotonic
      action of oxytocin. The presence in the circulation of extrahypothalamic
      corticotrophin-releasing hormone (CRH) produced by the placenta and myometrium is
      an inciting unique feature of primate pregnancy and a promising field for
      research. The concept of anatomical regionalization in labor promotion, including
      the cervical physiological inflammatory reaction, is also discussed in the
      review, especially in support of the strong link between inflammatory activation
      and onset of preterm labor. Understanding the intimate chain of events leading to
      parturition is critical, and elucidating the interplay of signals and processes
      that initiate normal labor may help us to understand the abnormal variant,
      spontaneous preterm labor, and devise efficacious interventions against it.

PMID- 18336277
TI  - Biomarkers in the exhaled breath condensate of healthy adults: mapping the path
      towards reference values.
AB  - The need for non-invasive assessment of airway inflammation is imperative, since
      inflammatory airway diseases, such as asthma and COPD, are characterized by
      variation in their clinical presentation throughout their course. Exhaled breath
      condensate (EBC) collection represents a rather appealing method that can be used
      to conveniently and noninvasively collect a wide range of volatile and non
      volatile molecules from the respiratory tract, without affecting airway function
      or inflammation. Although promising, EBC is currently used only as a research
      tool, due to the lack of appropriate standardization and the absence of reference
      values. The large number of measurable biomarkers and the diversity of the used
      methodologies are some of the points that hamper its wide clinical application.
      This review focuses mainly on the presentation of normal values of the most
      widely studied EBC markers as reported by investigators that have used healthy
      subjects as controls or as a basic study population. These biomarkers include
      hydrogen peroxide, NO-related products, arachidonic acid metabolites and pH. From
      those biomarkers, the only one with established reference values in healthy
      subjects is EBC pH, whereas the majority of the rest need further refinement and
      standardization of the methodologies used. Different subpopulations and the
      effect of various factors on healthy subjects are also reported, in an effort to
      delineate future directions that may lead to the establishment of reference
      values.

PMID- 18336278
TI  - Malignant mesothelioma resistance to apoptosis: recent discoveries and their
      implication for effective therapeutic strategies.
AB  - Malignant Mesothelioma is an aggressive and fatal type of tumor. The incidence of
      mesothelioma has increased in the past 30 years and is now common as male cancers
      of the liver, bone and bladder, especially in Europe and Australia. The main risk
      factor is asbestos exposure even if other co-factor, such as simian virus 40
      (SV40) could be implied in its etiology. Unfortunately, its incidence is expected
      to continue to increase for the next decades, also in rapidly industrializing
      countries, such as India, where it is not recognised as an occupational disease.
      Furthermore, some disastrous events, such as the World Trade Center Disaster, may
      contribute to increase future risk for mesothelioma. The treatment-resistant
      phenotype of mesothelioma is largely due to its ability to escape from the highly
      regulated apoptotic machinery. The understanding of the molecular mechanisms
      responsible of the malignant mesothelioma resistance to apoptosis is now
      advancing, allowing developing new therapeutic strategies to change the natural
      history and improve survival of patients. This review gives an overview of the
      main anti-apoptotic strategies devised by malignant mesothelioma and the
      therapeutic implication and opportunities for this cancer.

PMID- 18336279
TI  - The role of 11beta-hydroxysteroid dehydrogenase in metabolic disease and
      therapeutic potential of 11beta-hsd1 inhibitors.
AB  - Glucocorticoids play an essential role in the regulation of multiple
      physiological processes, including energy metabolism, maintenance of blood
      pressure and stress responses, as well as cognitive functions. On a tissue
      specific level, glucocorticoid action is controlled by 11beta-hydroxysteroid
      dehydrogenase enzymes. The type 1 enzyme (11beta-HSD1) is a NADP(H)-dependent
      bidirectional enzyme in vitro and reduces cortisone to active cortisol in vivo.
      11beta-HSD1 is expressed in many tissues including the liver, adipose and
      skeletal muscles. Chronically elevated local glucocorticoid action as a result of
      increased 11beta-HSD1 activity has been associated with the metabolic syndrome,
      which is characterized by obesity, insulin resistance, type 2 diabetes and
      cardiovascular complications. Recent studies indicate that the inhibition of
      11beta-HSD1 mitigates the adverse effects of excessive glucocorticoid levels on
      metabolic parameters and provides promising opportunities for the development of
      therapeutic interventions. This review discusses recently disclosed 11beta-HSD1
      inhibitors and their potential for the treatment of metabolic disorders.

PMID- 18336280
TI  - Nicotinamide adenine dinucleotide based therapeutics.
AB  - Nicotinamide adenine dinucleotide (NAD), generally considered a key component
      involved in redox reactions, has been found to participate in an increasingly
      diverse range of cellular processes, including signal transduction, DNA repair,
      and post-translational protein modifications. In recent years, medicinal chemists
      have become interested in the therapeutic potential of molecules affecting
      interactions of NAD with NAD-dependent enzymes. Also, enzymes involved in de novo
      biosynthesis, salvage pathways, and down-stream utilization of NAD have been
      extensively investigated and implicated in a wide variety of diseases. These
      studies have bolstered NAD-based therapeutics as a new avenue for the discovery
      and development of novel treatments for medical conditions ranging from cancer to
      aging. Industrial and academic groups have produced structurally diverse
      molecules which target NAD metabolic pathways, with some candidates advancing
      into clinical trials. However, further intensive structural, biological, and
      medical studies are needed to facilitate the design and evaluation of new
      generations of NAD-based therapeutics. At this time, the field of NAD
      therapeutics is most likely at a stage similar to that of the early successful
      development of protein kinase inhibitors, where analogs of ATP (a more widely
      utilized metabolite than NAD) began to show selectivity against target enzymes.
      This review focuses on key representative opportunities for research in this
      area, which extends beyond the scope of this article.

PMID- 18336281
TI  - Therapeutic potential of group III metabotropic glutamate receptors.
AB  - Metabotropic glutamate (mGlu) receptors have received much attention, driven by a
      strong belief in the potential of these modulatory glutamate receptors as drug
      targets. So far, major drug discovery programs have largely focused on group I
      (mGlu1 and 5) and II (mGlu2 and 3) mGlu receptors, which have been implicated in
      neuropathological and various psychiatric disorders. The four group III
      representatives (mGlu4, mGlu6, mGlu7 and mGlu8) are less understood, mainly due
      to the paucity of specific compounds. Recent advances in the identification of
      selective or specific compounds, and the generation of transgenic animals have,
      however, revealed important insights into the potential role of group III
      receptors in the pathophysiology of neurological and mood disorders. Activation
      of the mGlu4 receptor seems to be beneficial for treating Parkinson-like symptoms
      and a potential role in the treatment of mood disorders is slowly growing.
      Similarly, genetic inactivation studies and usage of relatively selective
      agonists strongly support the involvement of the mGlu8 receptor for anxiety
      disorders. In contrast, controversial data have been obtained for the mGlu7
      receptor. While mGlu7 receptor-deficient animals show an anxiolytic profile in
      several in vivo readouts, the first selective allosteric agonist AMN082 has also
      been reported to improve anxiety-like behaviour despite activating the stress
      axis. The least investigated receptor remains the mGlu6 receptor, which is mostly
      based on its predominant expression in the retina.

PMID- 18336282
TI  - Polyelectrolyte multilayer films: from physico-chemical properties to the control
      of cellular processes.
AB  - Polyelectrolyte multilayer films have been well characterized for almost two
      decades and there is now a growing interest for the development of biomimetic
      films that could be used in vitro or in vivo to control cellular behaviors. In
      this review, the important properties of multilayer films designed for
      cell/surface interactions will be highlighted. The first part will deal with the
      physico-chemical properties of polypeptide and polysaccharide multilayer films,
      including their growth, swellability, stability and mechanical properties. In the
      second part, we will focus on important properties influencing cellular
      behaviors: i) film biodegradability, ii) film mechanical properties, iii) film
      bioactivity achieved by either the intrinsic properties of the film components or
      the insertion of small peptides, proteins, or DNA. In particular, films thicker
      than one micron are particularly well suited for loading bioactive molecules due
      to their reservoir capacities.

PMID- 18336283
TI  - The role of oxytocin in neuropsychiatric disorders.
AB  - Oxytocin (OT) is a neurohypophysial hormone synthesized in the paraventricular
      and supraoptic nuclei of the hypothalamus. Although OT-like substances have been
      identified in all vertebrates, OT has been found only in mammals where it plays a
      major role in the onset and maintaining of behaviors which are typical of these
      animals, such as labour and lactation. Recently, several data have suggested the
      involvement of OT in the formation of infant attachment, maternal behavior, pair
      bonding and, more generally, in linking social signals with cognition, behaviors
      and reward. The aim of this paper was to review critically the role of OT in the
      regulation of different physiological functions and complex behaviors, as well as
      its possible involvement in the pathophysiology of some neuropsychiatric
      disorders. MEDLINE and PubMed (1972-2007) databases were searched for English
      language articles by using the following keywords: oxytocin, physiology,
      cognitive functions, attachment, psychopathology, psychiatric disorders. Papers
      were examined that addressed the following aspects of the OT system: synthesis
      and localization, receptors, physiology: In addition, latest findings showing
      abnormalities of OT and OT system in several neuropsychiatric disorders,
      including autism, obsessive-compulsive disorder, eating disorders, addiction,
      schizophrenia, post-traumatic stress disorder and Prader-Willy syndrome, will be
      also discussed together with the possible clinical use of OT or its analogues
      and/or antagonists.

PMID- 18336284
TI  - Platensimycin: a promising antimicrobial targeting fatty acid synthesis.
AB  - Platensimycin was recently discovered by Merck Research Laboratories and has
      created considerable interest given its potent antibacterial activity and mode of
      action. The use of RNA gene-silencing techniques and screening libraries of
      natural products allowed Merck to find this antibiotic which may have otherwise
      been missed using conventional methods. Interestingly, platensimycin has shown
      good activity against a panel of Gram positive organisms which included various
      resistant strains. Platensimycin works by inhibiting beta-ketoacyl synthases I/II
      (FabF/B) which are key enzymes in the production of fatty acids required for
      bacterial cell membranes. So far, a number of groups have explored synthetic
      strategies for platensimycin and this work has subsequently lead to the synthesis
      of active analogues. Given its mode of action, it is intriguing as to why Merck
      themselves patented only a single compound and have not apparently sought to
      generate further libraries. This review will discuss the origins of
      platensimycin, its mechanism of action, synthetic schemes and where the future
      may take us following this fascinating discovery.

PMID- 18336285
TI  - A possible placental factor for preeclampsia: sFlt-1.
AB  - Despite its clinical importance, the mechanism of preeclampsia is unclear;
      however, many believe placental pathology might be related to maternal systemic
      disease. If this is true, a factor which mediates information from the placenta
      to the maternal circulation can be hypothesized. Among a variety of such reported
      factors, soluble fms-like tyrosine kinase-1 (sFlt1) will be the focus of this
      review. The hypoxic placenta, which is commonly found in preeclampsia, produces
      sFlt1; furthermore, animal experiments suggest its over-expression leads to
      preeclampsia-like symptoms.

PMID- 18336286
TI  - Lung transplantation: the role of azithromycin in the management of patients with
      bronchiolitis obliterans syndrome.
AB  - Bronchiolitis obliterans syndrome (BOS) is the leading cause of death in lung
      transplant recipients (LTR). BOS is thought to result from chronic
      immunologic/inflammatory insults leading to peri-bronchiolar leukocyte
      infiltration, with a subsequent exuberant tissue re-modelling and fibro
      obliteration of the luminal space of the allograft airways. Diagnosis is based on
      functional criteria and severity is graded on the degree of Forced Expiratory
      Volume in 1 second (FEV1) impairment. Current strategies to improve pulmonary
      function once BOS is established have demonstrated little or no impact on disease
      progression and re-transplantation remains the only therapeutic option. Among the
      alternative treatments which have been attempted in the last few years, long-term
      azithromycin treatment seems to be the most promising therapeutic device for BOS
      treatment. Azithromycin is a macrolide antibiotic, endowed with a broad spectrum
      of anti-inflammatory/immunomodulatory activities. Long-term oral azithromycin
      therapy can significantly improve FEV1 in about 42% of patients with established
      BOS. Moreover, reduced neutrophilia, chemokine release and bacterial
      exacerbations have been demonstrated. These observations suggest that the drug
      can down-regulate pulmonary inflammation, even if the precise underlying
      mechanisms still need to be determined.

PMID- 18336287
TI  - Expression, regulation and function of asporin, a susceptibility gene in common
      bone and joint diseases.
AB  - Asporin is an extracellular matrix protein that belongs to the small leucine-rich
      repeat proteoglycan (SLRP) family of proteins. It is unique among SLRPs in that
      it lacks a glycosaminoglycan attachment site and contains an asparatic acid (D)
      repeat at its amino terminus. Its biological role has been unclear, but recent
      genetic studies have demonstrated association between asporin and various bone
      and joint diseases, including osteoarthritis, rheumatoid arthritis and lumbar
      disc disease. Each of these common diseases presents a substantial medical,
      social and economical burden to societies worldwide. This paper reviews recent
      progress in the study of asporin, focusing on its expression, regulation and
      function as well as its role in the molecular pathogenesis of common bone and
      joint diseases. Asporin is found primarily in regions surrounding skeletal tissue
      and is up-regulated in disease states. It binds to various growth factors,
      including TGF-beta and BMP-2, and negatively regulates their activity. By
      inhibiting binding of TGF-beta1 to its type II receptor, asporin forms a
      functional feedback loop with TGF-beta1 and regulates its chondrogenic potential.
      As an extracellular, tissue-specific protein, asporin represents a promising
      target for phamacogenomic approaches to common bone and joint diseases.

PMID- 18336288
TI  - Apoptosis, necrosis and autophagy: from mechanisms to biomedical applications.

PMID- 18336289
TI  - To die or not to die: that is the autophagic question.
AB  - Macroautophagy (commonly referred to as autophagy) is the process by which intact
      organelles and/or large portions of the cytoplasm are engulfed within double
      membraned autophagic vacuoles for degradation. Whereas basal levels of autophagy
      ensure the physiological turnover of old and damaged organelles, the massive
      accumulation of autophagic vacuoles may represent either an alternative pathway
      of cell death or an ultimate attempt for cells to survive by adapting to stress.
      The activation of the autophagic pathway beyond a certain threshold may promote
      cell death directly, by causing the collapse of cellular functions as a result of
      cellular atrophy (autophagic, or type II, cell death). Alternatively, autophagy
      can lead to the execution of apoptotic (type I) or necrotic (type III) cell death
      programs, presumably via common regulators such as proteins from the Bcl-2
      family. On the other hand, limited self-eating can provide cells with metabolic
      substrates to meet their energetic demands under stressful conditions, such as
      nutrient deprivation, or favor the selective elimination of damaged (and
      potentially dangerous) organelles. In these instances, autophagy operates as a
      pro-survival mechanism. The coordinate regulation of these opposite effects of
      autophagy relies upon a complex network of signal transducers, most of which also
      participate in non-autophagic signaling cascades. Thus, autophagy occupies a
      crucial position within the cell's metabolism, and its modulation may represent
      an alternative therapeutic strategy in several pathological settings including
      cancer and neurodegeneration. Here, we present a general outline of autophagy
      followed by a detailed analysis of organelle-specific autophagic pathways and of
      their intimate connections with cell death.

PMID- 18336290
TI  - Autophagy: for better or for worse, in good times or in bad times.
AB  - Autophagy is a bulk cytosolic degradative process which in the last few years has
      become a key pathway for the advancement of molecular medicine. Autophagy
      (cellular self-eating) has several implications in human disorders involving
      accumulation of cytosolic protein aggregates such as Alzheimer, Parkinson,
      Huntington diseases, as well as in myopathies caused by deficient lysosomal
      functions and in cancer. Moreover, autophagy affects intracellular microorganism
      lifespan, acting either as a cellular defense mechanism or, on the contrary,
      promoting pathogen replication. Furthermore, autophagy also participates in
      antigen presentation, as a part of the adaptive immune response. Therefore,
      autophagy association with cell survival or cell death would depend on cell
      nutrition conditions, presence of cell intruders, and alterations in oncogene or
      suppressor gene expression. In this review we will focus on the wide spectra of
      disease-related topics where autophagy is involved, particularly, in those
      processes concerning microorganism infections.

PMID- 18336291
TI  - Regulation of Bcl-2 family proteins by posttranslational modifications.
AB  - Like many proteins, function and abundance of Bcl-2 family proteins are
      influenced by posttranslational modifications. These modifications include
      phosphorylation, proteolytic cleavage, ubiquitination, and proteosomal
      degradation. These modifications, depending on cellular context and the proteins
      involved, can result either in a promotion of inhibition of apoptosis. Many of
      these modifications are governed by the activity of enzymes. As modulation of
      enzymatic activity can be achieved fairly efficiently using small molecules,
      understanding the effects of posttranslational modifications may allow for the
      therapeutic inhibition or promotion of apoptosis.

PMID- 18336292
TI  - Ca2+ signaling, mitochondria and cell death.
AB  - In the complex interplay that allows different signals to be decoded into
      activation of cell death, calcium (Ca2+) plays a significant role. In all
      eukaryotic cells, the cytosolic concentration of Ca2+ ions ([Ca2+]c) is tightly
      controlled by interactions among transporters, pumps, channels and binding
      proteins. Finely tuned changes in [Ca2+]c modulate a variety of intracellular
      functions ranging from muscular contraction to secretion, and disruption of Ca2+
      handling leads to cell death. In this context, Ca2+ signals have been shown to
      affect important checkpoints of the cell death process, such as mitochondria,
      thus tuning the sensitivity of cells to various challenges. In this contribution,
      we will review (i) the evidence supporting the involvement of Ca2+ in the three
      major process of cell death: apoptosis, necrosis and autophagy (ii) the complex
      signaling interplay that allows cell death signals to be decoded into
      mitochondria as messages controlling cell fate.

PMID- 18336293
TI  - Mitochondrial dynamics: to be in good shape to survive.
AB  - Mitochondria are essential organelles of all eukaryotic cells that play a key
      role in several physiological processes and are involved in the pathology of many
      diseases. These organelles form a highly dynamic network, which results from
      continuous fusion and fission processes. Importance of these processes is
      underlined by inherited human diseases caused by mutations in two mitochondrial
      pro-fusion genes: Charcot-Marie-Tooth disease, caused by mutations in Mitofusin 2
      gene and ADOA due to mutations in OPA1. During apoptosis, the mitochondrial
      network is disintegrated and the outer mitochondrial membrane permeabilized,
      which results in the release of several apoptogenic proteins, including
      cytochrome c. Although modulating mitochondrial fusion and fission machineries
      has been reported to influence the apoptotic response to various stimuli, it is
      still unclear whether fission is absolutely required for apoptosis. In this
      review, we present the latest progress in the field of mitochondrial dynamics
      with a particular emphasis on its implication in apoptosis and in diseases.

PMID- 18336294
TI  - Unique biology of Mcl-1: therapeutic opportunities in cancer.
AB  - Accumulating evidence suggests that Mcl-1 plays a critical pro-survival role in
      the development and maintenance of both normal and malignant tissues. Regulation
      of Mcl-1 expression occurs at multiple levels, allowing for either the rapid
      induction or elimination of the protein in response to different cellular events.
      This suggests that Mcl-1 can play an early role in response to signals directing
      either cell survival or cell death. Deregulation of pathways regulating Mcl-1
      that result in its over-expression likely contribute to a cell's inability to
      properly respond to death signals possibly leading to cell immortalization and
      tumorigenic conversion. Correspondingly, Mcl-1 has been shown to be up-regulated
      in numerous hematological and solid tumor malignancies. Moreover, this up
      regulation appears to be a factor in the resistance of some cancer types to
      conventional cancer therapies. Mechanisms that abrogate the pro-survival function
      of Mcl-1 either by diminishing its levels or inactivating its functional BH3
      groove have shown promise for the combinational treatment with existing cancer
      therapies and as single agents in certain malignancies. Here we review the
      various pathways that regulate Mcl-1 expression and describe agents that are
      currently under development to modulate Mcl-1 activity for therapeutic benefit in
      oncology.

PMID- 18336295
TI  - The Bax Inhibitor-1 (BI-1) family in apoptosis and tumorigenesis.
AB  - The signaling pathways that determine the fate of a cell regarding death or
      survival depend on a large number of regulatory proteins. The Bax Inhibitor-1 (BI
      1) family is a highly preserved family of small transmembrane proteins located
      mostly in the endoplasmic reticulum (ER). Although most members of this family
      are still not characterized an antiapoptotic effect has been described for BI-1,
      Lifeguard (LFG), and the Golgi anti-apoptotic protein (GAAP). The cytoprotective
      activity has been associated to the control of ion homeostasis and ER stress but
      includes other cell death stimuli as well. Recent data describes multiple
      interactions between the proteins of the BI-1 family and the Bcl-2 family either
      stimulating the antiapoptotic function of Bcl-2 or inhibiting the proapoptotic
      effect of Bax. The potent cell death suppression makes this protein family an
      interesting target for the development of new drugs and gene therapeutic
      approaches for diseases caused by apoptotic dysregulation, such as cancer.

PMID- 18336296
TI  - Histone deacetylase inhibitors.

PMID- 18336297
TI  - Chemical origins of isoform selectivity in histone deacetylase inhibitors.
AB  - Histones undergo extensive posttranslational modifications that affect gene
      expression. Acetylation is a key histone modification that is primarily regulated
      by two enzymes, one of which is histone deacetylase (HDAC). The activity of HDAC
      causes transcriptional silencing of DNA. Eleven distinct zinc-dependent histone
      deacetylase isoforms have been identified in humans. Each isoform has a unique
      structure and function, and regulates a unique set of genes. HDAC is responsible
      for the regulation of many genes involved in cancer cell proliferation, and it
      has been implicated in the pathogenesis of many neurological conditions. HDAC
      inhibitors are known to be very effective anti-cancer agents, and research has
      shown them to be potential treatments for many other conditions. Histone
      deacetylase inhibitors modify the expression of many genes, and it is possible
      that inhibition of one isoform could cause epigenetic changes that are beneficial
      to treatment of a disease, while inhibition of another isoform could cause
      contradictory changes. Selective HDAC inhibitors will be better able to avoid
      these types of situations than non-specific inhibitors, and may also be less
      toxic than pan-HDAC inhibitors. Many potent pan-HDAC inhibitors have already been
      developed, leaving the development of selective inhibitors at the forefront of
      HDAC drug development. Certain structural moieties may be added to HDAC
      inhibitors to give isoform selectivity, and these will be discussed in this
      review. This review will focus on the applications of selective HDAC inhibitors,
      inhibitors reported to show selectivity, and the relationship between inhibitor
      structure and selectivity.

PMID- 18336298
TI  - Isoform-selective histone deacetylase inhibitors.
AB  - Histone deacetylases (HDACs) catalyze the deacetylation of the acetylated lysine
      residues of histones and non-histone proteins, and are involved in various
      fundamental life phenomena, such as gene expression and cell cycle progression.
      Thus far, eighteen HDAC family members have been identified and they can be
      divided into two categories, i.e., zinc-dependent enzymes (HDAC1-11) and NAD(+)
      dependent enzymes (SIRT1-7). Some of the HDAC isoforms have important roles in
      cell functions, and are associated with various disease states, including cancer.
      Therefore, isoform-selective HDAC inhibitors are of great interest, not only as
      tools for probing the biological functions of the isoforms, but also as candidate
      therapeutic agents with few side effects. In this review, we cover isoform
      selective HDAC inhibitors, including their biochemical and pharmacological
      functions.

PMID- 18336299
TI  - From natural products to small molecule ketone histone deacetylase inhibitors:
      development of new class specific agents.
AB  - Histone deacetylases (HDACs) are one of two counteracting enzyme families whose
      activity controls the acetylation state of lysine protein residues, notably those
      contained in the N-terminal extensions of the core histones. Deregulation of the
      acetylation state of specific lysine residues has been implicated in a multitude
      of biologic processes, notably cancer, where HDACs are known to be involved in
      the control of cell cycle progression, cell survival and differentiation. HDAC
      inhibitors are being developed as anti-neoplastic agents. Nature has led the way
      in the development of these compounds, with trichostatin A being the first
      hydroxamic acid HDAC inhibitor identified. Likewise, the disulfide depsipeptide
      Romidepsin is currently in clinical trials, while an array of cyclic
      tetrapeptides HDAC inhibitors have been reported. Rational drug design has
      allowed these cyclic tetrapeptide to be transformed into equally potent small
      molecule inhibitors selective for either class I or class II HDACs. While acyclic
      alkyl ketones have been demonstrated to be selective HDAC 1, 2 and 3 inhibitors
      with efficacy in xenograft models, trifluoromethyl ketones have been shown to be
      selective inhibitors for class II HDACs and recently have been revealed to bind
      in the active site of the enzyme in their hydrated form.

PMID- 18336300
TI  - Fibrate-associated adverse effects beyond muscle and liver toxicity.
AB  - Fibrate derivatives have a 40-year history in the management of dyslipidemia.
      Although this class of drugs is generally well tolerated, several safety issues
      have arisen from their use. In the present article we review the literature
      describing side effects associated with the use of fibrates except for those that
      are liver and muscle related. These effects are less well known but are
      clinically relevant.

PMID- 18336301
TI  - Inhibitors of NAD+ dependent histone deacetylases (sirtuins).
AB  - Histone deacetylases (HDACs) are enzymes that deacetylate acetyl lysines in
      histones and various non-histone proteins. Three classes of histone deacetylases
      have been described in humans: class I, II and IV were shown to be zinc dependent
      amidohydrolases and eleven subtypes are known today (HDAC1-11). Class III enzymes
      depend in their catalysis on NAD+ with the subsequent formation of nicotinamide
      and O acetyl-ADP ribose. Based on the homology to the yeast histone deacetylase
      Sir2p the NAD+-dependent deacetylases have been termed sirtuins and seven members
      (SIRT1-7) have been described in humans. Whereas class I and II HDACs have been
      identified as valid anticancer targets and clinical studies of their inhibitors
      as new anticancer agents are under way much less is known about the consequences
      of class III histone deacetylase inhibition. Sirtuins have been linked to ageing
      and overexpression of sirtuins leads to a prolonged lifespan in yeast. Lately,
      sirtuin activity has been tied to the pathogenesis of HIV, cancer and
      neurodegenerative disease. In the last two years several reports of new sirtuin
      inhibitors have emerged. Additionally, sirtuin activators have been identified
      and have been implicated as potential drugs for the amelioration of metabolic
      diseases. Thus, the field of sirtuin biology can be investigated with these new
      tools which will allow in turn to assess the therapeutic potential of those
      compounds. We will present an overview over sirtuins and their available
      inhibitors and activators.

PMID- 18336302
TI  - Computational analysis of the interaction between ligand-receptor pairs.
AB  - Understanding the interactions between protein receptor-ligand pairs is of great
      pharmaceutical interest for structure-based drug design. It has become apparent
      that identifying interesting ligand-receptor pairs by computational techniques
      can offer new insights into functional studies of uncharacterized proteins. More
      importantly, the matching protein families of ligands and their receptors make it
      possible more easily to identify the ligands of orphan receptors. Unfortunately,
      there are few literature reports of the problem of ligand-receptor pairs
      systematically. In this paper, we will focus on current silico approaches that
      have been applied for protein ligand-receptor pair prediction. More specifically
      examples of chemokine receptor-ligand pairs are provided to illustrate the
      successful application of computational methods for protein ligand-receptor pair
      research, in particular for current bottlenecks and future directions of this
      field are discussed finally.

PMID- 18336303
TI  - Role of toll-like receptors in immune responses to chlamydial infections.
AB  - Chlamydiae are important human pathogens which are leading causative agents for a
      variety of disease conditions including ocular, respiratory and sexually
      transmitted diseases, thus causing significant morbidity worldwide. Many of the
      human diseases caused by Chlamydia species are considered to be
      immunopathologically mediated. Toll like receptors (TLRs) have emerged as one of
      the major components of the immune system. Recognition of pathogen associated
      molecular patterns (PAMPs) by TLRs results in the activation of signaling events
      that induce the expression of effector molecules such as cytokines and chemokines
      which control the activation of adaptive immune responses. The precise immune
      mechanisms involved in resistance or pathogenesis to chlamydial infection,
      especially in the TLR signaling and downstream events during the innate phase of
      infection initiating the adaptive immune responses remains largely unknown. This
      review focuses on elaborating the current knowledge on the role of TLRs in immune
      responses to chlamydial infection. Although chlamydial components like
      lipopolysaccharide (LPS) and chlamydial heat shock protein 60 (cHSP60) are
      recognized by TLR4, the intact organisms stimulates the innate immune cells
      through TLR2, which also plays an important role as a PRR for Chlamydia. While
      the individual role of different TLRs such as TLR2, TLR4 and TLR9 in chlamydial
      infection is becoming delineated, studies have demonstrated the essential role of
      the TLR adapter molecule MyD88 in the generation of immune responses to Chlamydia
      infection. Given that there is no effective vaccine available for Chlamydia till
      date, a better understanding of the immunological and molecular mechanisms
      mediated by TLRs will greatly aid in possibly exploiting these molecules as
      immunotherapeutic targets.

PMID- 18336304
TI  - Carbonic anhydrases as drug targets.
AB  - Carbonic anhydrases (CAs), the metalloenzymes that catalyze the conversion
      between carbon dioxide and bicarbonate, continue to be surprising targets, as
      many exciting new discoveries related to them emerge constantly. This is indeed
      unprecedented as these are quite "old" enzymes, which were discovered in 1933,
      and thoroughly investigated since then as drug targets. Furthermore, their
      inhibitors are in clinical use since the 50s. However, in the last years, a host
      of interesting reports were made regarding the catalytic/inhibition mechanism as
      well as isolation/characterization of new isozymes belonging to this family, as
      well as of CAs of non-vertebrate origin.

PMID- 18336305
TI  - Carbonic anhydrases--an overview.
AB  - Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes all over the
      phylogenetic tree, with at least 4 distinct gene families encoding for them. At
      least 16 different alpha-CA isoforms were isolated in mammals, where these
      enzymes play crucial physiological roles. Representatives of the beta-delta-CA
      family are highly abundant in plants, diatoms, eubacteria and archaea. These
      enzymes are efficient catalysts for the reversible hydration of carbon dioxide to
      bicarbonate, but at least the alpha-CAs possess a high versatility, being able to
      catalyze different other hydrolytic processes The catalytic mechanism of the
      alpha-CAs is understood in detail: the active site consists of a Zn(II) ion co
      ordinated by three histidine residues and a water molecule/hydroxide ion. The
      latter is the active species, acting as a potent nucleophile. For beta- and gamma
      CAs, the zinc hydroxide mechanism is valid too, although at least some beta-class
      enzymes do not have water directly coordinated to the metal ion. CAs are
      inhibited by two classes of compounds: the metal complexing anions and the
      sulfonamides and their isosteres (sulfamates, sulfamides etc.) possessing the
      general formula RXSO(2)NH(2) (R = aryl; hetaryl; perhaloalkyl; X = nothing, O or
      NH). At least 25 clinically used drugs/agents in clinical development show
      applications as diuretics and antiglaucoma drugs, anticonvulsants, with some
      compounds being developed as anticancer agents/diagnostic tools for tumors,
      antiobesity agents, and antimicrobials/antifungals (inhibitors targeting CAs from
      pathogenic organisms such as Helicobacter pylori, Mycobacterium tuberculosis,
      Plasmodium falciparum, Candida albicans, etc). Several important physiological
      and physio-pathological functions are played by CA isozymes present in organisms
      all over the phylogenetic tree, related to respiration and transport of
      CO(2)/bicarbonate between metabolizing tissues and the lungs, pH and CO(2)
      homeostasis, electrolyte secretion in a variety of tissues/organs, biosynthetic
      reactions, such as the gluconeogenesis and ureagenesis among others (in animals),
      CO(2) fixation (in plants and algae), etc. The presence of these ubiquitous
      enzymes in so many tissues and in so different isoforms, represents an attractive
      goal for the design of inhibitors or activators with biomedical applications.

PMID- 18336306
TI  - Design of zinc binding functions for carbonic anhydrase inhibitors.
AB  - Zinc ion plays a crucial role in the protein's functions and is linked to a
      variety of physiological processes. It constitutes an essential component of
      numerous enzymes especially carbonic anhydrase (CAs, EC 4.2.1.1), a
      pharmaceutically-important metalloprotein which catalyses efficiently the
      reversible hydration of carbon dioxide to bicarbonate with discharge of a proton.
      The potential therapeutic applications of selective carbonic anhydrase inhibitors
      has become an important challenge over the last few years, as some isoforms of
      this enzyme on the 16 described in higher vertebrates have been found to be
      involved in important pathologies such as cancer, obesity and ophthalmologic
      diseases. Coordination of the inhibitor with the zinc ion present in the active
      site is an important determinant which has to be taken into consideration for the
      design of isozyme-specific and organ-selective inhibitors. Besides the well known
      sulfonamide function, others zinc binding groups have been described constituting
      a new platform for the development of novel pharmacological agents. In this
      review, recent studies on the discovery of new zinc binding function will be
      discussed.

PMID- 18336307
TI  - The alpha and beta classes carbonic anhydrases from Helicobacter pylori as novel
      drug targets.
AB  - Helicobacter pylori (H. pylori) successfully resides in the human stomach in
      highly acidic conditions, causing a variety of gastroduodenal lesions, including
      gastric ulcer, gastric cancer and MALT lymphoma. For acid acclimation of H.
      pylori, two types of enzymes, urease and carbonic anhydrase (CA), play a central
      role. They cooperatively function to maintain neutral pH in the bacterial
      cytoplasm and periplasm. The genome project of H. pylori identified two different
      classes of CA with different subcellular localization: a periplasmic alpha-class
      CA (hp alphaCA) and a cytoplasmic beta-class CA (hp betaCA). These two CAs are
      catalytically efficient with almost identical activity to that of the human
      isoform CA I for the CO(2) hydration reaction, and highly inhibited by many
      sulfonamides/sulfamates, including acetazolamide, ethoxzolamide, topiramate and
      sulpiride, all clinically used drugs. Furthermore, certain CA inhibitors, such as
      acetazolamide and methazolamide, were shown to inhibit the bacterial growth in
      vitro. Since the efficacy of eradication therapies currently employed has been
      decreasing due to drug resistance and side effects of the commonly used drugs,
      the dual inhibition of alpha- and/or beta-CAs of H. pylori could be applied as an
      alternative therapy in patients with H. pylori infection or for the prevention of
      gastroduodenal diseases provoked by this widespread pathogen.

PMID- 18336308
TI  - The alpha-carbonic anhydrase from the malaria parasite and its inhibition.
AB  - Plasmodium falciparum is the protozoan parasite responsible for the majority of
      life-threatening cases of human malaria, causing more than one million deaths a
      year. The global emergence of drug-resistant malarial parasites necessitates
      identification and characterization of novel drug targets. At present, alpha
      carbonic anhydrase (CA) genes are identified in limited numbers of parasites in
      both protozoa and helminthes, however, the malarial genes are found in four
      species of Plasmodium. The CA gene of P. falciparum encodes an alpha-carbonic
      anhydrase enzyme possessing catalytic properties distinct of that of the human
      host CA I and II isozymes. P. falciparum native and recombinant enzymes have been
      prepared. A library of aromatic sulfonamides, most of which were Schiff's bases
      derived from sulfanilamide/homosulfanilamide/4-aminoethyl-benzenesulfonamide and
      substituted-aromatic aldehydes, or ureido-substituted sulfonamides are very good
      inhibitors for P. falciparum enzyme with K(i) values in the range of 80 nM-0.50
      microM. The 4-(3,4-dichlorophenylureido-ethyl)-benzenesulfonamide is the most
      effective antimalarial activity against growth of P. falciparum in vitro with an
      IC(50) of 2 microM. The structure of the groups substituting the aromatic-ureido-
      or aromatic-azomethine fragment of the molecule and the length of the parent
      sulfonamide (i.e., from sulfanilamide to 4-aminoethylbenzenesulfonamide) from
      which the Schiff's base obtained, are the critical parameters for the enzyme
      inhibitory activities of these aromatic sulfonamide derivatives, both against the
      malarial as well as human enzymes. This review provides further support that the
      CA may have essential roles in the parasite metabolism. Thus, the aromatic
      sulfonamide CA inhibitors may have potential for development of novel
      antimalarial drugs.

PMID- 18336309
TI  - Diuretics: from classical carbonic anhydrase inhibitors to novel applications of
      the sulfonamides.
AB  - The widely clinically used benzothiadiazines and high ceiling diuretics, such as
      hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone,
      chlorthalidone, indapamide, furosemide and bumetanide, contain SO(2)NH(2)
      moieties acting as an effective zinc-binding function in carbonic anhydrases
      (CAs, EC 4.2.1.1) inhibitors. These drugs were launched in a period when only
      isoform CA II was known and considered physiologically/pharmacologically
      relevant. Although acting as moderate-weak inhibitors of CA II, all these drugs
      considerably inhibit other CA isozymes known nowadays to be involved in critical
      physiologic processes, among the 16 CAs present in vertebrates. Some low
      nanomolar (or even subnanomolar) inhibitors against such isoforms were recently
      detected, such as metholazone against CA VII, XII and XIII, chlorthalidone
      against CA VB, VII, IX, XII and XIII, indapamide against CA VII, IX, XII and
      XIII, furosemide against CA I, II and XIV, and bumethanide against CA IX and XII.
      The X-ray crystal structure of the CA II-indapamide adduct was also reported
      recently, revealing interesting aspects useful for the drug design of CA
      inhibitors. It has also been proposed that the recently observed beneficial
      effect of indapamide for the treatment of patients with hypertension and type 2
      diabetes might be due to its potent inhibition of CA isoforms present in kidneys
      and blood vessels, which would thus explain both the blood pressure lowering
      effects as well as organ-protective activity of the drug. Thus, these old drugs
      may be useful as leads for new applications.

PMID- 18336310
TI  - The development of topically acting carbonic anhydrase inhibitors as antiglaucoma
      agents.
AB  - Inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms present in the eyes
      (CA I, II, IV and XII), with sulfonamides such as acetazolamide, methazolamide,
      ethoxzolamide and dichlorophenamide, is still widely used for the systemic
      treatment of glaucoma. The mechanism of action of these drugs consists in
      inhibition of CA isozymes present in ciliary processes of the eye, with the
      consequent reduction of bicarbonate and aqueous humour secretion, and of elevated
      intraocular pressure (IOP) characteristic of this disease. As isoforms CA
      II/IV/XII are present in many other tissues/organs, generally, systemic CAIs
      possess undesired side effects such as numbness and tingling of extremities;
      metallic taste; depression; fatigue; malaise; weight loss; decreased libido;
      gastrointestinal irritation; metabolic acidosis; renal calculi and transient
      myopia. For avoiding these side effects, recently, topically effective CAIs have
      been developed in the last 10 years, with two drugs available clinically:
      dorzolamide and brinzolamide. Both these drugs are applied topically as water
      solutions/suspensions, alone or in combination with other agents (beta-blockers,
      prostaglandin derivatives, etc) and produce a consistent and prolonged reduction
      of IOP. Furthermore, recent reports show both the systemically as well as
      topically acting sulfonamide CAIs to be effective in the treatment of macular
      edema, macular degeneration disease, or diabetic retinopathy, for which
      pharmacological treatment is unavailable up to now. Much research is in act in
      the search of more effective topically acting CAIs, free of the inconveniences
      and side effects of the presently available drugs. For achieving this goal, two
      recently reported strategy, the tail approach and its variant, the sugar-tail
      approach, were extensively applied for the synthesis of large numbers of
      derivatives possessing desired physico-chemical properties. Many such new
      sulfonamides showed promising antiglaucoma activity in animal models of the
      disease.

PMID- 18336311
TI  - Are carbonic anhydrase inhibitors suitable for obtaining antiobesity drugs?
AB  - Obesity is widespread disease both in the developed and developing world, which
      currently affects over 300 million individuals worldwide and is associated with
      premature mortality and chronic morbidity. Although diet, physical activity and
      behavioral modifications should theoretically help in controlling this condition,
      very often these strategies are insufficient to normalize the multiple risks
      associated with this condition. Thus, pharmacological interventions for the
      treatment of this disease are essential. Paradoxically, the currently available
      drugs for the treatment of obesity are very few, their mechanism of action is
      hardly understood and their side effects are generally quite serious. Therefore,
      novel effective anti-obesity drugs possessing different mechanisms of action are
      needed. In this review we describe in detail a possible new approach for the
      treatment and prophylaxis of this disease based on the inhibition of Carbonic
      Anhydrases (CAs, EC 4.2.1.1), enzymes involved in several steps of de novo
      lipogenesis. In particular, we summarize here a series of kinetic and structural
      studies recently reported on Topiramate (TPM) and Zonisamide (ZNS), two
      antiepileptic drugs showing strong CA inhibitory properties, that were shown to
      induce persistent weight loss in obese patients. On the basis of the reviewed
      studies we suggest that the use of TPM and ZNS as lead molecules for the design
      of CA inhibitors targeting isozymes involved in lipogenesis could represent the
      beginning of a very promising approach for the treatment of obesity.

PMID- 18336312
TI  - Anticonvulsant sulfonamides/sulfamates/sulfamides with carbonic anhydrase
      inhibitory activity: drug design and mechanism of action.
AB  - The marketed antiepileptic drugs can not solve entirely the problem of seizure in
      patients suffering from refractory epilepsies. Therefore, new anticonvulsant
      compounds structurally and pharmacologically different of the currently
      prescribed drugs are needed. Carbonic anhydrase (CA) inhibitors are known to act
      as anticonvulsant since several decades while the link between CA and seizure is
      not straightforward. However, the recent discovery that several CA isozymes are
      expressed in brain and the better knowledge of their physiological/pathological
      role, lead to the emergence of new CA inhibitors with anticonvulsant effect
      including: analogues of acetazolamide, analogues of topiramate, aromatic or
      heterocyclic sulfonamides incorporating valproyl or adamantyl moieties. Different
      strategies are developed for the design of new more selective CA inhibitors with
      anticonvulsant properties.

PMID- 18336313
TI  - Recent advances in research on the most novel carbonic anhydrases, CA XIII and
      XV.
AB  - The carbonic anhydrase (CA) enzyme family consists of thirteen active isozymes in
      mammals. The most recently characterized members of this family are cytosolic CA
      XIII and membrane-bound CA XV. This article describes recent advances in the CA
      family, especially CA XIII and XV. We have also included catalytic activity data
      on human CA XIII and mouse CA XV. Additionally, the inhibition constants of
      acetazolamide toward these isozymes were determined to be k(cat) = 1.5 x 10(5) s(
      1), k(cat)/K(M) = 1.1 x 10(7) M(-1) s(-1) and K(I) = 16 nM for human CA XIII and
      k(cat) = 4.7 x 10(5) s(-1), k(cat)/K(M) = 3.3 x 10(7) M(-1) s(-1) and K(I) = 72
      nM for mouse CA XV. Although the activity of CA XIII is the second lowest
      reported thus far for any of the human CAs, it may have a role in maintaining the
      acid-base balance in the kidney and the gastrointestinal and reproductive tracts.
      CA XV is an exceptional enzyme, as it seems to be active in numerous species,
      such as rodents, birds and fish, but is absent from humans and chimpanzees. Mouse
      CA XV is a moderately active enzyme, suggesting that it may play a physiological
      role at least in the kidney. It is likely that other isozymes have substituted
      for this protein in humans. In addition to the novel data on CA XIII and XV, we
      present the catalytic activities as well as inhibition constants of acetazolamide
      for all mammalian CA isozymes in this review.

PMID- 18336314
TI  - Carbonic anhydrase inhibition: insight into non-COX-2 pharmacological effect of
      some coxibs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most commonly used
      medications for the treatment of pain and inflammation, but numerous well
      described adverse drug reactions (ADRs) limit their use. These drugs act via the
      inhibition of cyclooxygenase (COX) enzyme of which at least two isoforms were
      described: COX-1 which plays important roles in homeostatic processes such as
      thrombogenesis and homeostasis of the gastrointestinal tract and kidneys and COX
      2 expressed in pathological conditions such as inflammation or cancer
      proliferation. Selective COX-2 inhibitors or "coxibs" were initially developed as
      a therapeutic strategy to avoid not only the gastrointestinal but also the renal
      and cardiovascular side effects of non specific NSAIDs. However, this class of
      drug did not fulfill all their promises. Indeed, numerous unexpected side effects
      have limited their use and some of them have been withdrawn or suspended from the
      market for different safety reasons including cardiovascular, hepatic and skin
      adverse reactions. For instance, cardiovascular warnings have been applied to the
      whole class of coxibs and more recently for all classical NSAIDs as well.
      However, differences in the chemical structures should be taken into
      consideration in order to discriminate between coxibs and the development of some
      ADRs of which renal events and hypertension. The aim of this paper is to focus on
      the differences in chemical structures of all marketed COX-2 inhibitors and their
      unexpected effects on carbonic anhydrase in order to provide non-COX-2
      mechanistic insights into some of the differences observed between coxibs.

PMID- 18336315
TI  - Cancer-associated carbonic anhydrases and their inhibition.
AB  - Cells of the growing tumor tissue are exposed to physiological stresses connected
      with insufficient delivery of oxygen (hypoxia) and accumulation of acidic
      products of the glycolytic metabolism (acidosis). Adaptation to these
      microenvironmental stresses involves remodeling of the cellular expression
      program mediated by hypoxia-inducible factor (HIF), which activates broad array
      of genes functionally involved in angiogenesis, anaerobic glycolysis, de
      adhesion, invasion etc. This leads to increased aggressiveness of tumors,
      metastatic spread and poor response to therapy. Genes coding for transmembrane
      carbonic anhydrase (CA) isoforms IX and XII are induced in response to low oxygen
      as a part of the hypoxic transcriptome. Moreover, CA IX is a direct target of HIF
      and serves as a surrogate marker of hypoxia and prognostic indicator. Its
      expression is strongly linked to different types of tumors with the HIF pathway
      activated due to genetic defect or physiological hypoxia. CA IX (and possibly
      also CA XII) is participates in pH regulation, which is important for survival of
      hypoxic cells. Both enzymes are therefore promising therapeutic molecules
      targetable by inhibitors of CA activity. Some of these sulfonamide compounds and
      their derivatives are capable to block CA-mediated pH regulation in hypoxia. This
      review summarizes research data related to distribution, regulation and
      functional aspects of CA IX and CA XII, and describes emerging possibilities for
      clinical exploitation of CA inhibitors as imaging tools and anticancer drugs.

PMID- 18336316
TI  - Fluorescence- and spin-labeled carbonic anhydrase inhibitors.
AB  - Carbonic anhydrase IX (hCA IX) is a membrane-associated glycoprotein that is
      observed in many tumor tissues and is strongly overexpressed by hypoxia
      conditions. Hypoxia is a clinically important tumor parameter and this enzyme can
      play an important role as a potential marker of hypoxic tumor and as a
      therapeutic target too. In the last years, Carbonic Anhydrase IX Inhibitors which
      possess fluorescent probe were largely used for visualize hypoxic tumor cell
      lines and for understanding the biological roles of hCA IX in acidification of
      the external matrix. Here we resume the development pathways of such compounds
      from the design to the final biological evaluation. Furthermore, spin-labeled
      CAIs were included to have a complete overview of the potentiality of this enzyme
      as marker of hypoxic tumors.

PMID- 18336317
TI  - Carbonic anhydrase activation and the drug design.
AB  - The activation mechanism of Carbonic Anhydrase was recently explained using
      kinetic, spectroscopic and X-ray techniques. It has been demonstrated that the
      activators molecules (CAAs) bind at the entrance of the enzyme active-site
      facilitating the rate-determining step of CA catalytic cycle. Drug design studies
      have been performed in order to obtain strong CAAs belonging to several chemical
      classes: amino acids, azoles, amine and their derivatives, etc. Structure
      activity correlations of different activators are discussed for the most studied
      Carbonic Anhydrase isozymes: isoform I and II. The physiological relevance of CA
      activation and the possible application of CAAs in Alzheimer's disease and for
      other memory therapies are also treated.

PMID- 18336318
TI  - The beta and gamma classes of carbonic anhydrase.
AB  - There are currently five (alpha, beta, gamma, delta, zeta) classes of carbonic
      anhydrases (CA's) of which the alpha-class from mammalian sources has been
      studied to a much greater extent compared to the other four classes. Yet, CA's
      other than the alpha-class are widely distributed in Nature and play important
      roles in human health, the global carbon cycle, and industrial applications. In
      aerobic prokaryotes, beta-class CA's are implicated in maintaining internal pH
      and CO(2)/bicarbonate balances required for biosynthetic reactions. In anaerobic
      prokaryotes, beta-class CA's are implicated in the transport of CO(2) and
      bicarbonate across the cytoplasmic membrane that regulates pH and facilitates
      acquisition of substrates and product removal required for growth. In
      phototrophic organisms, beta-class CA's are particularly important for transport
      and concentration of CO(2) and bicarbonate for photosynthesis. The delta- and
      zeta-classes are proposed to function in marine diatoms to concentrate CO(2) for
      photosynthesis. Physiological roles for the gamma-class are not as well
      documented; however, the active site architecture and catalytic mechanism is well
      understood as are patterns of inhibition by sulfonamides and anions.

PMID- 18336319
TI  - Recent progress and future directions in protein-protein docking.
AB  - This article gives an overview of recent progress in protein-protein docking and
      it identifies several directions for future research. Recent results from the
      CAPRI blind docking experiments show that docking algorithms are steadily
      improving in both reliability and accuracy. Current docking algorithms employ a
      range of efficient search and scoring strategies, including e.g. fast Fourier
      transform correlations, geometric hashing, and Monte Carlo techniques. These
      approaches can often produce a relatively small list of up to a few thousand
      orientations, amongst which a near-native binding mode is often observed.
      However, despite the use of improved scoring functions which typically include
      models of desolvation, hydrophobicity, and electrostatics, current algorithms
      still have difficulty in identifying the correct solution from the list of false
      positives, or decoys. Nonetheless, significant progress is being made through
      better use of bioinformatics, biochemical, and biophysical information such as
      e.g. sequence conservation analysis, protein interaction databases, alanine
      scanning, and NMR residual dipolar coupling restraints to help identify key
      binding residues. Promising new approaches to incorporate models of protein
      flexibility during docking are being developed, including the use of molecular
      dynamics snapshots, rotameric and off-rotamer searches, internal coordinate
      mechanics, and principal component analysis based techniques. Some investigators
      now use explicit solvent models in their docking protocols. Many of these
      approaches can be computationally intensive, although new silicon chip
      technologies such as programmable graphics processor units are beginning to offer
      competitive alternatives to conventional high performance computer systems. As
      cryo-EM techniques improve apace, docking NMR and X-ray protein structures into
      low resolution EM density maps is helping to bridge the resolution gap between
      these complementary techniques. The use of symmetry and fragment assembly
      constraints are also helping to make possible docking-based predictions of large
      multimeric protein complexes. In the near future, the closer integration of
      docking algorithms with protein interface prediction software, structural
      databases, and sequence analysis techniques should help produce better
      predictions of protein interaction networks and more accurate structural models
      of the fundamental molecular interactions within the cell.

PMID- 18336320
TI  - Activation, exposure and penetration of virally encoded, membrane-active
      polypeptides during non-enveloped virus entry.
AB  - Host cell entry by influenza and other enveloped viruses is well characterized,
      however, the manner in which non-enveloped viruses deliver their genome across
      host cell membranes in the absence of membrane fusion remains unresolved. The
      discovery of short, membrane altering, amphipathic or hydrophobic sequences in
      several non-enveloped virus capsid proteins such as the gamma (gamma) peptide of
      nodaviruses and tetraviruses, VP4 and the N-terminal region of VP1 of
      picornaviruses, micro1N of reoviruses, and protein VI of adenoviruses suggests
      that these small peptides facilitate breaching of the host membrane and the
      delivery of the viral genome into the host cell. In spite of conspicuous
      differences in entry among non-enveloped virions, the short stretches of membrane
      active regions are associated with similar, entry-related events including: I)
      proteolytic cleavage of a precursor capsid protein resulting in increased dynamic
      character and/or accessibility of these peptides; II) structural changes in the
      virus capsid triggered by receptor binding and/or low pH in entry compartments,
      resulting in peptide exposure; III) externalized peptides interact with host
      membranes and disrupt them, facilitating delivery of the viral genome inside the
      host cell. Here we discuss the membrane alteration activity in non-enveloped
      viruses with reference to the gamma peptide of nodaviruses. Virtually all of the
      characteristics of gamma are shared by analogous peptides in other non-enveloped
      viruses, making it a simple prototype for comparative purposes.

PMID- 18336321
TI  - Proteins as networks: usefulness of graph theory in protein science.
AB  - The network paradigm is based on the derivation of emerging properties of studied
      systems by their representation as oriented graphs: any system is traced back to
      a set of nodes (its constituent elements) linked by edges (arcs) correspondent to
      the relations existing between the nodes. This allows for a straightforward
      quantitative formalization of systems by means of the computation of mathematical
      descriptors of such graphs (graph theory). The network paradigm is particularly
      useful when it is clear which elements of the modelled system must play the role
      of nodes and arcs respectively, and when topological constraints have a major
      role with respect to kinetic ones. In this review we demonstrate how nodes and
      arcs of protein topology are characterized at different levels of definition: 1.
      Recurrence matrix of hydrophobicity patterns along the sequence 2. Contact matrix
      of alpha carbons of 3D structures 3. Correlation matrix of motions of different
      portion of the molecule in molecular dynamics. These three conditions represent
      different but potentially correlated reticular systems that can be profitably
      analysed by means of network analysis tools.

PMID- 18336322
TI  - Lantibiotic immunity.
AB  - Lantibiotics are a diverse family of bacterially synthesized antimicrobial
      peptides produced by gram-positive bacteria. They usually have a broad spectrum
      of targets, often including closely related strains. The production of
      lantibiotics must thus be coupled with a mechanism by which the producing strain
      can protect itself from the lethal action of its own antimicrobial compound. This
      mechanism is referred to as immunity. Lantibiotic immunity is usually provided by
      one, or both, of two methods i.e. by a specific immunity peptide (designated
      LanI) and/or a specialised ABC transporter system (designated LanFE(G)).
      Significantly, although the specific immunity peptides function in a similar
      manner, there is very little homology between them. This is reflected in the
      specific nature of the immunity provided. Finally, of equal importance is the
      manner in which these immunity determinants are regulated such that their
      expression is timed to occur with, or immediately prior to, lantibiotic
      production to ensure successful self-protection.

PMID- 18336323
TI  - NMR of membrane-associated peptides and proteins.
AB  - In living cells, membrane proteins are essential to signal transduction, nutrient
      use, and energy exchange between the cell and environment. Due to challenges in
      protein expression, purification and crystallization, deposition of membrane
      protein structures in the Protein Data Bank lags far behind existing structures
      for soluble proteins. This review describes recent advances in solution NMR
      allowing the study of a select set of peripheral and integral membrane proteins.
      Surface-binding proteins discussed include amphitropic proteins, antimicrobial
      and anticancer peptides, the HIV-1 gp41 peptides, human alpha-synuclein and
      apolipoproteins. Also discussed are transmembrane proteins including bacterial
      outer membrane beta-barrel proteins and oligomeric alpha-helical proteins. These
      structural studies are possible due to solubilization of the proteins in membrane
      mimetic constructs such as detergent micelles and bicelles. In addition to
      protein dynamics, protein-lipid interactions such as those between arginines and
      phosphatidylglycerols have been detected directly by NMR. These examples
      illustrate the unique role solution NMR spectroscopy plays in structural biology
      of membrane proteins.

PMID- 18336324
TI  - Homology-free prediction of functional class of proteins and peptides by support
      vector machines.
AB  - Protein and peptide sequences contain clues for functional prediction. A
      challenge is to predict sequences that show low or no homology to proteins or
      peptides of known function. A machine learning method, support vector machines
      (SVM), has recently been explored for predicting functional class of proteins and
      peptides from sequence-derived properties irrespective of sequence similarity,
      which has shown impressive performance for predicting a wide range of protein and
      peptide classes including certain low- and non- homologous sequences. This method
      serves as a new and valuable addition to complement the extensively-used
      alignment-based, clustering-based, and structure-based functional prediction
      methods. This article evaluates the strategies, current progresses, reported
      prediction performances, available software tools, and underlying difficulties in
      using SVM for predicting the functional class of proteins and peptides.

PMID- 18336325
TI  - Structure, function and biological relevance of prolyl oligopeptidase.
AB  - A group of serine peptidases, the prolyl oligopeptidase family, cannot hydrolyze
      proteins and peptides containing more than 30 residues. The crystal structure of
      prolyl oligopeptidase (POP) has shown that the enzyme is composed of a peptidase
      domain with an alpha/beta hydrolase fold and a seven-bladed beta-propeller
      domain. This domain covers the catalytic triad and excludes large, structured
      peptides from the active site. The mechanism of substrate selection has been
      reviewed, along with the binding mode of the substrate and the catalytic
      mechanism, which differ from that of the classical serine peptidases in several
      features. POP is essentially a cytosolic enzyme and has been shown to be involved
      in a number of biological processes, but its precise function is still unknown.
      Many reports addressed experimentally the possible role of POP in cognitive and
      psychiatric processes, its involvement in the inositol phosphate signaling
      pathway, and its ability to metabolize bioactive peptides. Inhibitors were
      designed to reveal the cellular functions of POP and to treat neurological
      disorders. Other studies concerned the cellular localization of POP, its presumed
      interaction with the cytoskeletal elements, and its involvement in
      peptide/protein transport/secretion processes. The possible role of POP in
      Alzheimer disease is an intriguing issue, which is still debated. Recently,
      recombinant bacterial POPs have been investigated as potential therapeutics for
      celiac sprue, an autoimmune disease of small intestine caused by the intake of
      gluten proteins.

PMID- 18336326
TI  - Synthesis and cytotoxicity studies of new morpholino-functionalised and N
      heteroaryl-substituted titanocene anticancer drugs.
AB  - From the carbolithiation of 6-morpholino fulvene (3) and different lithiated
      nitrogen containing heterocycles (2-N-methylimidazolyl, 2-N-(N,N
      dimethylamino)methyl-imidazolyl, and 2-N-methylindolyl), the corresponding
      lithium cyclopentadienide intermediate (4a-c) was formed. These three lithiated
      intermediates underwent a transmetallation reaction with TiCl(4) resulting in
      morpholino-functionalised titanocenes 5a-c. When these titanocenes were tested
      against LLC-PK cells, the IC(50) values obtained were of 24, 36, and 41 microM
      respectively. The most cytotoxic titanocene in this paper (5a) with an IC(50)
      value of 24 microM is found to be almost ten times less cytotoxic than cis
      platin, which showed an IC(50) value of 3.3 microM when tested on the epithelial
      pig kidney LLC-PK cell line, and approximately 2 times less cytotoxic than its
      dimethylamino-functionalised analogue. Encouragingly however, the IC(50) value
      obtained for titanocene 5a is approximately 100 times better than titanocene
      dichloride itself.

PMID- 18336327
TI  - Photoperiod and testosterone modulate growth and melanogenesis of s91 murine
      melanoma.
AB  - In vivo and in vitro assays were performed with S91 murine melanoma cells aiming
      to investigate the effects of testosterone and photoperiod on tumor growth and
      melanogenesis (tyrosinase activity). In vivo assays were performed by inducing
      melanoma tumors in castrated mice receiving increasing concentrations of
      testosterone and submitted to varying photoperiod regimens. The results
      demonstrated that the increase of melanin content was higher in animals submitted
      to the longest days, thus demonstrating the importance of photoperiod length in
      melanin synthesis. Increase in tumor growth and protein content was observed in
      testosterone-treated animals submitted to 12L:12D; in testosterone-treated
      animals submitted to 4L:20D and 20L:4D tumor growth was significantly smaller. In
      S91 cultured cells, testosterone increased cell proliferation and reduced
      tyrosinase activity in a dose-dependent manner. Radioactive binding assays
      demonstrated that the hormone was acting through low affinity testosterone
      receptors, since the presence of aromatase inhibitor did not affect the binding
      assay in a statistically significant way, and all the in vitro experiments were
      performed in the presence of the inhibitor. Our in vivo data added to the in
      vitro results corroborate the hypothesis that S91 melanoma cells directly respond
      to testosterone and that this effect is modulated by light.

PMID- 18336328
TI  - Cytotoxic and apoptogenic activity of a methanolic extract from the marine
      invertebrate Ciona intestinalis on malignant cell lines.
AB  - Marine invertebrates provide a series of natural products with different
      biological activities. Several of these compounds and their derivatives showed a
      potent anticancer effect. Tunicates represent an important source of bioactive
      agents, leading to the isolation of ecteinascidin-743 (ET-743), a compound
      isolated from the Caribbean sea squirt Ecteinascidia turbinata with a potent
      cytotoxic activity against a variety of tumours in vitro and in vivo. Current
      phase II clinical trials against soft tissue sarcomas in Europe and the United
      States indicate that ET-743 represents a highly promising anticancer agent.
      Another example is aplidine from the Mediterranean tunicate Aplidium albicans,
      with a broad spectrum activity against various types of cancers, such as
      colorectal, lymphoma, thyroid and renal cancers. In the present work, we
      reported, for the first time, that a partially purified methanolic extract
      prepared from the ascidian Ciona intestinalis inhibited cell proliferation in
      human cell lines of different origin, including Caco2, HPB-ALL, U-937 and HL-60
      and induced early apoptotic events, such as caspase-3 activation and
      internucleosomal DNA degradation. We suggest the presence in the Ciona
      intestinalis extract of bioactive compounds possessing anticancer activity.

PMID- 18336329
TI  - Quantitative structure-activity relationships for commercially available
      inhibitors of COX-2.
AB  - Quantitative structure activity relationship (QSAR) studies of selective COX-2
      inhibitors of commercial interest (drugs in market and on clinical trials) were
      performed. The COX-2 inhibitory activity (pIC(50)=-logIC(50)) of these twelve
      compounds was correlated with nineteen descriptors including steric, electronic
      and constitutional parameters. pIC(50) activity showed high positive correlation
      with both volume and HOMO (Highest occupied molecular orbital). A Biparametric
      model was developed that included both these descriptors. The predictive
      capability (q(2)= 0.66) of this equation was satisfactory. So it can be used to
      design newer templates or modify existing templates. Volume is an important
      parameter for the selective COX-2 inhibitory activity, because the secondary
      pocket in the active site of this enzyme is bigger than the active site of COX-1
      enzyme (by 17%). HOMO is a measure of the nucleophilicity of the molecule and a
      molecule with high HOMO energy is ready to donate its electrons and thus is more
      reactive than molecule with low values. Binding studies were performed between
      the COX-2 enzyme and these molecules. The inhibitory activity increased with
      decrease in binding energy (or interaction energy) between the compounds with the
      COX-2 enzyme (with a correlation coefficient = -0.65). Calculated Log BBB (Blood
      Brain barrier), Log P (octonol water partition) and HBD (hydrogen bond donor)
      values were in the acceptable range (i.e., BBB = -1 to 0.3; LogP= 0 to 5; HBD <
      5).

PMID- 18336330
TI  - Inhibitory feature of the proprotein convertases prosegments.
AB  - The proprotein convertases (PCs) are serine proteases involved in various
      physiological processes and their overactivity or inactivity has been linked to
      different disorders. PCs are responsible for the proteolytic processing of
      various polypeptide precursors. Here, we discuss the effect of their N-terminal
      prosegments on various PC substrates processing and functions.

PMID- 18336331
TI  - Synthesis and pharmacological profile of a series of 1-substituted-2-carbonyl
      derivatives of Diphenidol: novel M4 muscarinic receptor antagonists.
AB  - Novel 2-carbonyl analogues of diphenidol (1) - bearing lipophylic 1-substituents
      (2) - were synthesized starting from previously investigated diphenidol
      derivatives acting as M(2)-selective muscarinic antagonists. These compounds were
      tested for receptor binding affinity versus human muscarinic M(1)-M(5) receptors
      stably expressed in CHO-K1 cells. Their activity in functional assays carried out
      on CHO-K1 cells expressing human M(4) receptors (CHO-hM(4)) and on classical
      models of M(1)-M(3) receptors, in guinea pig and rabbit tissue preparations, was
      also evaluated. Compound 2d showed an affinity of pK(i) = 7.73 at the human M(4)
      receptor subtype with selectivity ratios ranging from 31-fold (M(4)/M(5)) to 60
      fold (M(4)/M(2)). Interestingly this compound, in CHO-hM(4) cells, blocked the
      inhibition of forskolin-activated cAMP accumulation produced by carbachol
      (IC(50)= 61 nM) whereas it was a weak muscarinic antagonist in functional tests
      carried out in guinea-pig and rabbit tissue expressing M(1) (pK(b) = 5.96), M(2)
      (pK(b) = 6.43) and M(3) (pK(b) = 6.09) receptors. In conclusion, the
      modifications performed in this work on reference compounds led us to obtain
      surprisingly a M(4) selective antagonist. Considering the therapeutic indications
      for M(4) selective antagonists, compound 2d may serve as a novel lead compound
      for further optimization.

PMID- 18336332
TI  - Synthesis and endothelin receptor binding affinity of a novel class of 2
      substituted-4-aryl-3-quinolinecarboxylic acid derivatives.
AB  - The 21-amino acid peptide endothelin-1 (ET-1) is the predominant isoform of the
      endothelin peptide family, which includes ET-2, and ET-3. These peptides display
      a variety of physiological activities including vasoconstriction and the
      stimulation of cell proliferation in tissues both within and outside of the
      cardiovascular system. They exert their actions via activation of two distinct
      receptor subtypes, ET(A) and ET(B), belonging to the G protein-coupled receptor
      (GPCR) superfamily. Ligands of these receptors have received numerous citations
      in the recent pharmaceutical literature. In particular receptor antagonists, both
      ET(A)- and ET(B)-selective, as well as non-selective, have been described due to
      their wide therapeutic potential. As a part of our program toward the development
      of selective ET(A) ligands we have designed and we now report new molecules based
      on 2-substituted-4-aryl-3-quinolinecarboxylic acid moiety. Binding profile for
      some compounds (40, 44, 46, and 47) of this class showed a reasonable affinity
      and selectivity for ET(A) receptors.

PMID- 18336333
TI  - Comparative antiviral (HIV) photoactivity of metalized meso-
      tetraphenylsulfonated porphyrins.
AB  - We have carried out the study of the photochemical properties of a series of
      synthetic meso-tetraphenylsulfonated porphyrins (TPPMS4) bonded to several metal
      ions such as: Cu(II), Zn(II), Pd(II), Mn(II), Fe(III), Ni(II) and Co(II) for the
      optimization of their clinical applications as antiviral agents against the human
      immunodeficiency virus (HIV-1) as well as the study of the in vitro antiviral
      photoinactivation mechanisms with future application in blood sterilization. A
      selective inhibition has been determined in the viral growth (HIV-1) when this is
      irradiated in the presence of the complex TPPFeS4 and TPPMnS4 (photosensitizer
      mediated Type I reaction) as well as in the 1O2-mediated (Type II reaction) in
      the presence of TPPPdS4 and TPPZnS4, remaining cellular viability unaltered in
      each case.

PMID- 18336334
TI  - Synthesis of some thiophene, imidazole and pyridine derivatives exhibiting good
      anti-inflammatory and analgesic activities.
AB  - A series of thiophene derivatives 1a-d & 2a-c were synthesized by condensation of
      5-nitro-2-thiophene carboxaldehyde with mono and diamines respectively. Various
      imidazole derivatives 3a-c were obtained by condensing 4-(2-ethylamino)-1H
      imidazole with 4-acetylpyridine, 2-acetylpyridine and 4-acetylbenzonitrile
      respectively. Pyridine derivatives 4a-e were synthesized by condensing 2
      hydrazino-pyridine with various carbonyl compounds; 5a-c by condensing 2, 6
      pyridine dicarbonyl dichloride with various aryl sulfonylhydrazides; 6, 7 by
      condensing 2, 6-dialdehyde pyridine with 2-hydrazinopyridine and
      anthranilonitrile respectively and compound 8 by condensing 2, 5-thiophene
      dialdehyde with hydrazinopyridine. All the compounds were characterized by IR,
      (1)HNMR, Mass spectra and elemental analysis. Compounds 1a-d; 2a-c; 3a-c; 4a-e;
      5a-c, 6, 7 and 8 were screened for anti-inflammatory and analgesic activities.
      Compounds 1b and 2c exhibited good anti-inflammatory (26.5% and 33.4% at 50mg/kg
      p.o. respectively) and 3a, 3c good analgesic (100% and 75% at 100 mg/kg p.o.
      respectively) activities.

PMID- 18336335
TI  - Photoreactive DNA probes as a tool for studying the translesion synthesis system
      in Mammalian cell extracts.
AB  - Translesion synthesis (TLS) is one of the DNA damage tolerance strategies that
      has evolved to enable orga-nisms to replicate their genome despite the presence
      of unrepaired damage. TLS complexes are dynamic systems composed of DNA
      polymerases and associated protein factors. Therefore, it is hard to study these
      assembles by X-ray analysis or other instrumental methods. Here, we have
      suggested applying the photoaffinity labeling technique for studying the TLS
      system in nuclear/cellular extracts. As a tool we proposed to use partial DNA
      duplexes containing base-substituted photoreactive deoxynucleotides at the 3' end
      of primer opposite to DNA damage at the template strand. We demonstrated that
      photoreactive dNTPs can be potentially used to synthesize photoreactive DNA
      probes mimicking the DNA intermediates of the first stage of translesion
      synthesis by specialized DNA polymerases. We used synthetic apurinic/apyrimidinic
      site (AP-site) - tetrahydrofuran (THF) and 8 oxoguanine as damages in +1 position
      of the template strand with respect to 3' end of primer. Activity of human DNA
      polymerases beta and lambda was exploited for construction of photoreactive DNAs
      using photo derivatives of dNTPs. The kinetic parameters of the elongation
      reaction in model systems were estimated. Using photoaffinity crosslinking we
      found that only a few proteins in the bovine testis nuclear extract were strongly
      labeled by TLS probes.

PMID- 18336336
TI  - In vitro leishmanicidal activity of 3-substituted isocoumarins: synthesis and
      structure activity relationship.
AB  - Twenty-five 3-substituted isocoumarins were synthesized using cutting edge
      microwave-assisted technology in high yields. The syntheses of different
      isocoumarins were carried out in a single step by the direct condensation of
      homophthalic acid with aryol and acyl chlorides under the solvent-free conditions
      without any solid support. The structures of all the synthesized compounds were
      characterized using different spectroscopic techniques including UV, IR, (1)HNMR
      and EIMS and purity was confirmed by CHN analysis. All the synthesized compounds
      were tested for in vitro leishmanicidal activity. Compounds 3a, 3b, 3g, 3l, 3m,
      3r, 3t, 3w, 3x, and 3y displayed potential in vitro leishmanicidal activity with
      IC(50) values in the range of 0.56-84.38 microg/ml, whereas standard inhibitors
      amphotericine B have IC(50) = 0.24 microg/ml. The compounds 3b, 3g, 3m, 3t, 3w,
      3x, and 3y having IC(50) values 27.86, 28.88, 36.49, 34.37, 28.68, 0.89 and 0.56
      microg/ml, respectively, were most active among the present series while
      remaining others were found less active. The compound 3x and 3y can act as
      potential lead molecules for further development of isocoumarin-based new drugs
      for the treatment of leishmaniasis.

PMID- 18336337
TI  - Prediction of distribution of neutral, acidic and basic structurally diverse
      compounds between blood and brain by the nonlinear methodology.
AB  - The methodology for predicting the distribution of compounds between Blood and
      Brain, i.e. their brain/blood partition coefficients (logBB values), was studied
      using a nonlinear regression analysis in this work. The equations were
      established on the basis of the different states (neutral, cationic and anionic)
      of the compounds distributing into the three dominating composition (lipid,
      protein and water) of the brain. The equations bear strong fitting and predictive
      power for the distribution of compounds (total set: n=160, r=0.906, s=0.326;
      training set: n=139, r=0.908, s=0.320; testing set: n=21, r=0.903, s=0.297), and
      can describe the distribution of the different states of the compounds in three
      compositions of brain. The compounds in the dataset contained many different
      types, such as drug molecules, small structure-simple molecules, carboxylic acids
      and also alkaloids. Therefore the equations were very useful and instructional
      for the prediction of the compound distribution into the brain and blood.
      Finally, the percentages of the amount of a compound in lipid, protein and water
      in brain were calculated using the model, such subdivision will be very useful in
      drug research and discovery. By an analysis of the percentages a conclusion can
      be obtained that a well distributed drug is mainly affected by distribution of
      lipid and protein.

PMID- 18336338
TI  - Anti-tubercular and anti-inflammatory activities of azetidin-2-one derivatives
      and their effects on the activity of Phospholipase A2.
AB  - The title compounds have been synthesized and tested for structure activity
      relationship for Phospholipase A2 (PLA2) [E.C. 3.1.1.4] enzyme inhibition. The in
      vitro anti-tubercular, PLA(2) enzyme inhibitory activities of azetidin-2-one
      derivatives and in vivo anti-inflammatory studies using mice are highlighted. The
      analogues of azetidin-2-one were prepared based on the initial activity against
      Mycobacterium tuberculosis (Mtb). Certain azetidin-2-one analogues described
      herein showed moderate to good anti-tubercular activity. In particular, two
      compounds (4f) and (4g) exhibited MIC values of 1.56 and 0.78 microg/mL
      respectively against the Mtb H(37)Rv strain. Chloro substitution on aryloxy acid
      apparently enhanced the antimycobacterial activity and also PLA2 inhibition in
      the azetidin-2-one series described herein. The ability of azetidin-2-one
      analogues as anti-inflammatory agents has also been determined. The results show
      some correlation between anti-inflammatory, anti-tubercular activity and
      expression of PLA2 enzyme.

PMID- 18336339
TI  - Relationship between drugs and functional activity of various mammalian P
      glycoproteins (ABCB1).
AB  - P-glycoprotein (Pgp, ABCB1) is an efflux transporter for a variety of amphipathic
      agents that can affect the pharmacokinetics of drugs. In order to extrapolate
      transport and pharmacokinetic data of the drug candidates obtained from in vitro
      and animal models to those in humans, it is important to understand the
      functional differences of Pgps from various mammalian species including human,
      monkey, dog, rat, and mouse. Here, we review differences/similarities in the
      properties of Pgp from numerous mammalian species commonly used in preclinical
      studies and discuss their relevance to the pharmacokinetics of potential drug
      molecules.

PMID- 18336340
TI  - Malaria combination therapies: advantages and shortcomings.
AB  - Drug combination therapies have been devised to delay the development and spread
      of resistant malaria parasites. However, poor design often leads to ineffective
      combinations. Here, the properties of various drug combinations are reviewed in
      relationship to drug resistance and their pharmacokinetic compatibility.

PMID- 18336341
TI  - How the parts organize in the whole? A top-down view of molecular descriptors and
      properties for QSAR and drug design.
AB  - Sometimes the complexity of a system, or the properties derived from it, do
      depend neither on the individual characteristics of the components of the system
      nor on the nature of the physical forces that hold them together. In such cases
      the properties derived from the "organization" of the system given by the
      connectivity of its elements can be determinant for explaining the structure of
      such systems. Here we explore the necessity of accounting for these structural
      characteristics in the molecular descriptors. We show that graph theory is the
      most appropriate mathematical theory to account for such molecular features. We
      review a method (TOPS-MODE) that is able to transform simple molecular
      descriptors, such as logP, polar surface area, molar refraction, charges, etc.,
      into series of descriptors that account for the distribution of these
      characteristics (hydrophobicity, polarity, steric effects, etc) across the
      molecule. We explain the mathematical and physical principles of the TOPS-MODE
      method and develop three examples covering the description and interpretation of
      skin sensitisation of chemicals, chromosome aberration produced by organic
      molecules and drug binding to human serum albumin.

PMID- 18336342
TI  - Pharmacological neuroprotective therapy for acute spinal cord injury: state of
      the art.
AB  - After spinal cord injury, a number of destructive events developed immediately
      after the primary insult increase tissue damage. Several therapeutic approaches
      are directed to neutralize these phenomena. The present manuscript revises
      diverse pharmacological treatments used to promote neuroprotection, both in
      clinical and experimental acute spinal cord injuries.

PMID- 18336343
TI  - Cytidine deaminases as a weapon against retroviruses and a new target for
      antiviral therapy.
AB  - APOBEC3G (apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G) was
      identified as an anti-HIV-1 (human immunodeficiency virus type 1) cellular factor
      in target CD4 T cells. It is a member of the APOBEC family of cytidine deaminases
      consisting of APOBEC1, APOBEC2, APOBEC3 (A to H), and AID (activation induced
      deaminase). During reverse transcription, it deaminates dC to dU in nascent minus
      strand viral DNA, resulting in G-to-A hypermutation in the plus strand DNA to
      inhibit the replication of HIV-1. On the contrary, HIV-1 Vif protein counteracts
      this enzyme by the ubiquitin-proteasome pathway to enable HIV-1 replicate in
      target cells. Vif forms an E3 ligase complex with cellular proteins including
      Cullin5, ElonginB, and ElonginC (Vif-BC-Cul5) and functions as a substrate
      recognition subunit of the complex to target APOBEC3G for ubiquitin-proteasome
      dependent degradation in virus-producing cells. APOBEC3G has also been shown to
      have a broad antiviral activity on a wide variety of viruses which include not
      only retroviruses such as other lentiviruses, murine leukemia virus (MLV), and
      human T-cell leukemia virus type 1 (HTLV-1) but also other viruses such as
      hepatitis B virus (HBV) and adeno-associated virus. Furthermore, other members of
      the APOBEC family also show a broad antiviral activity, but target virus
      specificities vary among APOBEC members. On the other hand, viruses have their
      own mechanisms to escape from APOBEC. These expanding evidences suggest that the
      APOBEC family of cytidine deaminases plays an important role in antiviral innate
      immunity and might be a novel target for an antiviral therapy. Here we review the
      present understanding of APOBEC3 proteins as an antiviral innate immunity and
      battles between APOBEC3 and viruses.

PMID- 18336344
TI  - Inhibition of orotidine 5'-monophosphate decarboxylase and its therapeutic
      potential.
AB  - Orotidine 5'-monophosphate decarboxylase (ODCase) is among the most proficient
      enzymes, and catalyzes the decarboxylation of OMP to UMP. An overview of ODCase
      and various proposals for its catalytic mechanism of decarboxylation are briefly
      presented here. A number of inhibitors of ODCase and new developments in the X
      ray structures of ODCases from different species are discussed in the context of
      their therapeutic potential against cancer and infectious diseases. Latest
      discoveries in the inhibition of ODCase, for example using the novel C6
      substitutions on the uridine, open new doors for drug discovery targeting
      parasitic diseases such as malaria.

PMID- 18336345
TI  - Strategies for in vivo siRNA delivery in cancer.
AB  - A better understanding of the mechanisms involved in small interference RNA
      (siRNA) gene silencing opens new horizons for the development of the targeted
      therapy of malignant and benign diseases. As a research tool, siRNA has proven to
      be highly effective in silencing specific genes and modulating intracellular
      signaling pathways. However, systemic delivery of siRNA has been more problematic
      due to degradation and poor cellular uptake. In order to overcome these
      limitations, a variety of strategies are being developed including new delivery
      vehicles and chemical modifications. Here, we review potential approaches for the
      systemic delivery of siRNA for cancer treatment.

PMID- 18336346
TI  - HPLC as a tool in medicinal chemistry for the monitoring of tricyclic
      antidepressants in biofluids.
AB  - HPLC is discussed as an essential tool in medicinal chemistry for the monitoring
      of tricyclic antidepressants in biofluids, providing clinicians with efficient
      fast and reliable methods to define individual optimum therapeutic concentrations
      in treatment of depressions. Additional information on mechanism of action,
      structure activity relationship and metabolism is provided.

PMID- 18336347
TI  - The structure activity relationship of discodermolide analogues.
AB  - The marine polyketide discodermolide is a member of a class of natural products
      that stabilize microtubules. Many analogues have been synthesized suggesting that
      few changes can be made to the internal carbon backbone. Both ends of the
      molecule, however, can be modified. The majority of analogues have been generated
      via modification of the lactone region. This suggests that significant
      simplifications can be made in this region provided that the lactone moiety is
      maintained.

PMID- 18336348
TI  - Glycolipid stimulators for NKT cells bearing invariant V alpha 19-J alpha 33 TCR
      alpha chains.
AB  - Attempts have been made to find specific antigens for a novel NKT cell subset
      bearing invariant V alpha 19-J alpha 33 TCR alpha chains (V alpha 19 NKT cell).
      Comprehensive examinations revealed substantial antigenic activity in synthetic
      alpha-mannosylceramide (ManCer) that was presented by MR1. Structural
      modification of the sphingosine moiety of alpha-ManCer improved antigenic
      activity to enhance either Th1 or Th2 -promoting cytokine production by V alpha
      19 NKT cells. Such alpha-ManCer analogues will be useful for developing new
      therapies as immunomodulators.

PMID- 18336349
TI  - Low molecular weight inhibitors of the protease anthrax lethal factor.
AB  - Anthrax Lethal Factor (LF) is a zinc-dependent metalloprotease that together with
      the protective antigen constitute the anthrax lethal toxin, the most prominent
      virulence factor of the disease anthrax. This review summarizes the current
      knowledge on anthrax toxicity and defense in relation to LF. Particular emphasis
      is placed on the structural aspects of LF, the properties of its substrates and
      the achievements in the design of low molecular weight inhibitors of the
      catalytic activity of the metalloenzyme.

PMID- 18336350
TI  - Host defense peptides and the new line of defence against multiresistant
      infections.
AB  - Increasing antibiotic resistance has led to an urgent need for new therapeutic
      approaches. Host defense peptides are known to be antimicrobial and have revealed
      broad immunomodulatory functions for both innate and adaptive immunity. This
      review will focus on the role of host defense peptides in infection and immune
      response and discuss its potential and limitations as a future therapeutical
      agent.

PMID- 18336351
TI  - Conformational studies suggest that the double stranded beta helix scaffold
      provides an optimal balance between protein stability and function.
AB  - Proteins with the double stranded beta-helix (DSBH, also known as cupin) fold
      perform a diverse range of functions. In this study, Bacillus subtilis
      quercetinase was used as a model system to understand the conformational
      determinants of functional diversity within the cupin fold. Controlled
      proteolysis experiments revealed that this enzyme is active, thermo-stable and
      maintains its quaternary arrangement even after substantial (ca 33 %) cleavage of
      the protein. The results presented in this manuscript thus show that the DSBH
      scaffold offers a novel balance between protein stability and function by
      locating the active site and substrate recognition features in the most stable
      region of the protein.

PMID- 18336352
TI  - Normal cytochrome C oxidase activity in prion protein gene-deficient mice.
AB  - Cytochrome c oxidases of prion protein (PrP) gene-deficient (Prnp(-/-)) and
      Prnp(+/+) mice were examined in vivo and in vitro. Non-invasive near-infrared
      spectra revealed that oxidation of copper and heme a+a(3) in cytochrome c oxidase
      of Prnp(-/-) mice was similar to that in Prnp(+/+) mice. Biochemical analysis of
      mitochondrial fractions also supported the results. PrP might not be involved in
      regulation of cytochrome c oxidase.

PMID- 18336353
TI  - Stability and biological activity of human intestinal trefoil factor produced by
      Pichia pastoris.
AB  - Intestinal trefoil factor (ITF), a member of the trefoil factor family, plays an
      important role in protecting the epithelial layer of the intestinal tract from
      damage and repairing epithelium after injury. In the present study, we expressed
      recombinant hITF by Picha pastoris expression system in shake flasks to 50mg/L.
      rhITF was purified up to 95% by ammonium sulfate precipitation, Ni-NTA affinity
      chromatography and ultrafiltration. In conditions simulating intestinal tract
      environment, rhITF was shown to exhibit resistance to proteases, heat, acid and
      alkali. In addition, rhITF was found to be biologically active in an in vitro
      restitution model. This study lays the foundation for the commercial production
      of rhITF and provides theoretical evidence for the oral use of rhITF.

PMID- 18336354
TI  - Designing of substrates and inhibitors of bovine alpha-chymotrypsin with
      synthetic phenylalanine analogues in position P(1).
AB  - The primary specificity residue of a substrate or an inhibitor, called the P(1)
      residue, is responsible for the proper recognition by the cognate enzyme. This
      residue enters the S(1) pocket of the enzyme and establishes contacts (up to 50%)
      inside the proteinase substrate cavity, strongly affecting its specificity. To
      analyze the influence on bovine alpha-chymotrypsin substrate activity, aromatic
      non-proteinogenic amino acid residues in position P(1) with the sequence Ac-Phe
      Ala-Thr-X-Anb(5,2)-NH(2) were introduced: L-pyridyl alanine (Pal), 4
      nitrophenylalanine - Phe(p-NO(2)), 4-aminophenylalanine - Phe(p-NH(2)), 4
      carboxyphenylalanine Phe(p-COOH), 4-guanidine phenylalanine - Phe(p-guanidine), 4
      methyloxycarbonyl-phenylalanine - Phe(p-COOMe), 4-cyanophenylalanine - Phe(p-CN),
      Phe, Tyr. The effect of the additional substituent at the phenyl ring of the Phe
      residue was investigated. All peptides contained an amide of 5-amino-2
      nitrobenzoic acid, which served as a chromophore. Kinetic parameters (k(cat),
      K(M) and k(cat)/K(M)) of the peptides synthesized with bovine alpha-chymotrypsin
      were determined. The highest value of the specificity constant k(cat)/K(M),
      reaching 6.0 x 10(5) [M(-1)xs(-1)], was obtained for Ac-Phe-Ala-Thr-Phe(p-NO(2))
      Anb(5,2)-NH(2). The replacement of the acetyl group with benzyloxycarbonyl moiety
      yielded a substrate with the value of k(cat) more than three times higher.
      Peptide aldehydes were synthesized with selected residues (Phe, Pal, Tyr, Phe(p
      NO(2)) in position P(1) and potent chymotrypsin inhibitors were obtained. The
      dissociation constant (K(i)) with the experimental enzyme determined for the most
      active peptide, Tos-Phe-Ala-Thr-Phe(p-NO(2))-CHO, amounted to 1.12 x 10(-8) M.

PMID- 18336355
TI  - Surfactin isoforms from Bacillus subtilis HSO121: separation and
      characterization.
AB  - Natural surfactin is a mixture of cyclic lipopeptides built from variants of a
      heptapeptide and a beta-hydroxy fatty acid. A biosurfactant-producing strain,
      Bacillus subtilis HSO121, was isolated from the production water of an oil field.
      The strain was able to produce eight surfactin isoforms which have been isolated
      by acid-precipitation followed by extraction into methanol. A novel procedure for
      the purification of surfactin was achieved. It consists of a solid-phase
      extraction on C(18) gel followed by reversed-phase high performance liquid
      chromatography using Prep. HiQ sil C18W, column. The surfactin isoforms were
      eluted by linear acetonitrile gradient from 80-100%. The peaks were analyzed by
      TLC on silica gel, and after acid hydrolysis their amino acid compositions were
      determined by HPLC analysis. Eight isoforms of surfactin had nearly the same
      amino acid composition and appeared a single spot in TLC. According to the R(f)
      values with the amino acid composition, these peaks belong to the surfactin group
      of lipopeptides. Infrared analysis of the purified samples also revealed a
      pattern similar to that of surfactin. This is a very effective method for
      isolating and fractionating lipopeptides, of the same or different nature.

PMID- 18336356
TI  - Effects of a chitin binding vicilin from Erythrina velutina seeds on bean bruchid
      pests (Callosobruchus maculatus and Zabrotes subfasciatus).
AB  - Erythrina velutina vicilin, EvV, is a dimeric glycoprotein with Mr of 124.6 kDa.
      EvV was tested for anti-insect activity against bean bruchid larvae. EvV had
      LD(50) of 0.10% and ED(50) of 0.14% for Z. subfasciatus and LD(50) of 0.26% and
      ED(50) of 0.19% for C. maculatus. EvV was not digested by bean larvae enzymes
      until 12 h of incubation, and at 24 h EvV was more resistant to Z. subfasciatus
      enzymes.

PMID- 18336357
TI  - Structure-activity relationships of the dimeric analogues of endomorphin-2 with
      different lengths of spacers.
AB  - In the present study, seven novel dimeric analogues of endomorphin-2 with longer
      spacers were designed and synthesized. Through dimerization, their affinity for
      delta-opioid receptor was mostly increased, especially the delta-opioid receptor
      preferred dimeric analogue, DEM(12). The results were confirmed by the in vitro
      bioassay. The structure-activity relationships were also discussed.

PMID- 18336358
TI  - T and B-cell epitopes prediction of Iranian saffron (Crocus sativus) profilin by
      bioinformatics tools.
AB  - Plant profilins form a well-known panallergen family responsible for cross
      sensitization between plant foods and pollens. We sought to map T and B-cell
      epitopes on the Iranian Crocus sativus profilin by bioinformatics tools. The
      predicted peptides are useful for further vaccine development.

PMID- 18336359
TI  - Predicting subcellular localization with AdaBoost Learner.
AB  - Protein subcellular localization, which tells where a protein resides in a cell,
      is an important characteristic of a protein, and relates closely to the function
      of proteins. The prediction of their subcellular localization plays an important
      role in the prediction of protein function, genome annotation and drug design.
      Therefore, it is an important and challenging role to predict subcellular
      localization using bio-informatics approach. In this paper, a robust predictor,
      AdaBoost Learner is introduced to predict protein subcellular localization based
      on its amino acid composition. Jackknife cross-validation and independent dataset
      test were used to demonstrate that Adaboost is a robust and efficient model in
      predicting protein subcellular localization. As a result, the correct prediction
      rates were 74.98% and 80.12% for the Jackknife test and independent dataset test
      respectively, which are higher than using other existing predictors. An online
      server for predicting subcellular localization of proteins based on AdaBoost
      classifier was available on http://chemdata.shu. edu.cn/sl12.

PMID- 18336360
TI  - A docking modelling rationally predicts strong binding of bisphenol A to estrogen
      related receptor gamma.
AB  - A computer-aided docking study was carried out to quickly clarify the binding
      structure of the ligand-receptor complex between bisphenol A (BPA), a well-known
      endocrine disruptor, and estrogen-related receptor gamma (ERRgamma). The
      resulting complex indicated that BPA binds to the ligand-binding pocket of
      ERRgamma without any disruptions of the activation conformation.

PMID- 18336361
TI  - Stabilization of beta-propeller phytase by introducing Xaa-->Pro and Gly-->Ala
      substitutions at consensus positions.
AB  - Phytases play important roles in agricultural and feed industries. In this study,
      the stability of a beta-propeller phytase, PhyL, from Bacillus licheniformis was
      successfully improved by introducing Xaa-->Pro and Gly-->Ala substitutions at
      consensus positions. Our results suggest that Gly-->Ala substitution is a more
      promising strategy to improve protein stability.

PMID- 18336362
TI  - Recent advances and perceptions in studies of heterodimerization between G
      protein-coupled receptors.
AB  - G protein coupled-receptors (GPCR) have been shown to form heterodimers or
      heterooligomers with various biochemical and/or pharmacological activity that are
      distinct from those of the corresponding monomers or homomers. Recent in vitro
      and in vivo experimental data have also shown novel functional roles of several
      orphan GPCRs as modulatory units of heterodimers and potentials for development
      of heterodimer-selective clinical agents. In this review, we summarize essential
      and latest knowledge as to GPCR heterodimerizations and the current issues to be
      solved in the near future.

PMID- 18336363
TI  - Linear-polarized IR-spectroscopic and structural elucidation of glycyl-L
      phenylalanyl-glycine hydrochloride monohydrate.
AB  - As a part of our spectroscopic and structural elucidation of small peptides,
      their salts and metal complexes, the polarized IR-spectroscopic and structural
      elucidation of the protonated form of glycyl-(L)-phenylalanyl-glycine as
      hydrochloride monohydrate (H-Gly-Phe-Gly-OHxHClxH(2)O) is reported. The obtained
      structure of the protonated tripeptide is supported by quantum chemical ab initio
      calculations at UHF level of theory and 6-31++G, showing only one stable
      conformer with two intermolecular NH(3)(+)OH(2) and (C=O)OHOH(2) hydrogen bonds.
      The N(terminus) amide O=C-N-H amide fragment is flat trans-configured with a
      dihedral angle value of 179.0(7)degrees, while the corresponding group at
      C(terminus) is with transoide-configurated and value of the dihedral angle of
      151.1(3)degrees, respectively. In addition data of (1)H- and (13)C magnetic
      resonance spectroscopy (NMR), thermogravimetry (TGA), differential scanning
      calorimetry (DSC) and high performed liquid chromatography (HPLC) with tandem
      mass spectrometry (HPLC-MS/MS) as presented.

PMID- 18336364
TI  - Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified
      citrullinated vimentin antibodies in rheumatoid arthritis.
AB  - Several autoantibodies found in RA are directed to epitopes in citrullinated
      proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We
      tested the value a newly developed ELISA for the detection of antibodies against
      a genetically modified citrullinated vimentin (anti-MCV) in comparison with an
      anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA
      (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were
      enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/-
      6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects
      (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti
      MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP
      level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In
      patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV
      level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was
      11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with
      active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV
      level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum
      anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10
      U/ml. According to these results; In patients with RA, the mean serum anti-MCV
      and anti-CCP levels were significantly high compared to patients with AS and
      healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean
      serum anti-MCV and anti- CCP levels were significantly higher in active patients
      with RA than in inactive patients with RA patients (p=0.001 and p=0.001
      respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP
      levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09
      and p=0.222 respectively). The mean serum anti-MCV levels were correlated with
      DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001),
      serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen
      joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As
      a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and
      combined use of anti-MCV and RF may be more useful prognostic factor than either
      method alone, RF and anti-CCP.

PMID- 18336365
TI  - Purification, crystallization and preliminary analysis of hemoglobin from rabbit
      (Oryctolagus cuniculus).
AB  - Hemoglobin (Hb) is a tetrameric protein, which contains four heme prosthetic
      groups, and each one is associated with a polypeptide chain. Herein, we report
      the rabbit hemoglobin which has intrinsically high oxygen affinity and possess
      highest sequence identity with human hemoglobin. The purified hemoglobin has been
      tried to crystallize in different crystallization conditions owing to its
      formation of various crystal systems. The rabbit Hb crystals were grown using PEG
      3,350 as the precipitant at 18 degrees C. The crystals of rabbit Hb belongs to
      triclinic space group P1 with one molecule (alpha2beta2) in the asymmetric unit.

PMID- 18336366
TI  - Association between PPARalpha gene polymorphisms and myocardial infarction.
AB  - PPARalpha (peroxisome-proliferator-activated receptor alpha) regulates the
      expression of genes that are involved in lipid metabolism, tissue homoeostasis
      and inflammation. Consistent rodent and human studies suggest a link between
      PPARalpha function and cardiovascular disease, qualifying PPARalpha [PPARA in
      HUGO (Human Genome Organisation) gene nomenclature] as a candidate gene for
      coronary artery disease. In the present study, we comprehensively evaluated
      common genetic variations within the PPARalpha gene and assessed their
      association with myocardial infarction. First, we characterized the linkage
      disequilibrium within the PPARalpha gene in an initial case-control sample of 806
      individuals from the Regensburg Myocardial Infarction Family Study using a panel
      of densely spaced SNPs (single nucleotide polymorphisms) across the gene. Single
      SNP analysis showed significant association with the disease phenotype [OR (odds
      ratio)=0.74, P=0.012, 95% CI (confidence interval)=0.61-0.94 for rs135551].
      Moreover, we identified a protective three-marker haplotype with an association
      trend for myocardial infarction (OR=0.76, P=0.067, 95% CI=0.56-1.02).
      Subsequently, we were able to confirm the single SNP and haplotype association
      results in an independent second case-control cohort with 667 cases from the
      Regensburg Myocardial Infarction Family Study and 862 control individuals from
      the WHO (World Health Organization) MONICA (Monitoring of Trends and Determinants
      in Cardiovascular Disease) Augsburg project (OR=0.87, P=0.046, 95% CI=0.72-0.99
      for rs135551 and OR=0.80, P=0.034, 95% CI=0.65-0.98 for the three-marker
      haplotype respectively). From these cross-sectional association results, we
      provide evidence that common variations in the PPARalpha gene may influence the
      risk of myocardial infarction in a European population.

PMID- 18336367
TI  - Characterization of an ideal amphipathic peptide as a procoagulant agent.
AB  - On the basis of previous evidence that amphipathic helical peptides accelerate
      Factor IXa activation of Factor X [Blostein, Rigby, Furie, Furie and Gilbert
      (2000) Biochemistry 39, 12000-12006], the present study was designed to assess
      the procoagulant activity of an IAP (ideal amphipathic peptide) of Lys(7)Leu(15)
      composition. The results show that IAP accelerates Factor X activation by Factor
      IXa in a concentration-dependent manner and accelerates thrombin generation by
      Factor Xa with a comparable peptide- and substrate-concentration-dependence. A
      scrambled helical peptide with the same amino acid composition as IAP, but with
      its amphipathicity abolished, eliminated most of the aforementioned effects. The
      Gla (gamma-carboxyglutamic acid)-rich domain of Factor X is required for IAP
      activity, suggesting that this peptide behaves as a phospholipid membrane. This
      hypothesis was confirmed, using fluorescence spectroscopy, by demonstrating
      direct binding between IAP and the Gla-rich domain of Factor X. In addition, the
      catalytic efficiencies of the tenase and prothrombinase enzymatic complexes,
      containing cofactors Factor VIIIa and Factor Va respectively, are enhanced by
      IAP. Finally, we show that IAP delays clot lysis in vitro. In summary, these
      observations demonstrate that IAP not only enhances essential procoagulant
      reactions required for fibrin generation, but also inhibits fibrinolysis,
      suggesting a potential role for IAP as a haemostatic agent.

PMID- 18336368
TI  - Role of Chlamydia pneumoniae in atherosclerosis.
AB  - Cardiovascular disease, resulting from atherosclerosis, is a leading cause of
      global morbidity and mortality. Genetic predisposition and classical
      environmental risk factors explain much of the attributable risk for
      cardiovascular events in populations, but other risk factors for the development
      and progression of atherosclerosis, which can be identified and modified, may be
      important therapeutic targets. Infectious agents, such as Chlamydia pneumoniae,
      have been proposed as contributory factors in the pathogenesis of
      atherosclerosis. In the present review, we consider the experimental evidence
      that has accumulated over the last 20 years evaluating the role of C. pneumoniae
      in atherosclerosis and suggest areas for future research in this field.

PMID- 18336369
TI  - Killer cells in chronic obstructive pulmonary disease.
AB  - COPD (chronic obstructive pulmonary disease) is a treatable and preventable
      disease state, characterized by progressive airflow limitation that is not fully
      reversible. It is a current and growing cause of mortality and morbidity
      worldwide, with the WHO (World Health Organization) projecting that total deaths
      attributed to COPD will increase by more than 30% in the next 10 years. The
      pathological hallmarks of COPD are destruction of the lung parenchyma (pulmonary
      emphysema), inflammation of the central airways (chronic bronchitis) and
      inflammation of the peripheral airways (respiratory bronchiolitis). The
      destructive changes and tissue remodelling observed in COPD are a result of
      complex interactions between cells of the innate and adaptive immune systems. The
      focus of the present review is directed towards the role of CD8(+) T-lymphocytes,
      NK (natural killer) cells and NKT cells (NK T-cells). These three classes of
      killer cell could all play an important part in the pathogenesis of COPD. The
      observed damage to the pulmonary tissue could be caused in three ways: (i) direct
      cytotoxic effect against the lung epithelium mediated by the activities of
      perforin and granzymes, (ii) FasL (Fas ligand)-induced apoptosis and/or (iii)
      cytokine and chemokine release. The present review considers the role of these
      killer cells in COPD.

PMID- 18336370
TI  - Periodontal disease: associations with diabetes, glycemic control and
      complications.
AB  - OBJECTIVE: This report reviews the evidence for adverse effects of diabetes on
      periodontal health and periodontal disease on glycemic control and complications
      of diabetes. DESIGN: MEDLINE search of the English language literature identified
      primary research reports published on (a) relationships between diabetes and
      periodontal diseases since 2000 and (b) effects of periodontal infection on
      glycemic control and diabetes complications since 1960. RESULTS: Observational
      studies provided consistent evidence of greater prevalence, severity, extent, or
      progression of at least one manifestation of periodontal disease in 13/17 reports
      reviewed. Treatment and longitudinal observational studies provided evidence to
      support periodontal infection having an adverse effect on glycemic control,
      although not all investigations reported an improvement in glycemic control after
      periodontal treatment. Additionally, evidence from three observational studies
      supported periodontal disease increasing the risk for diabetes complications and
      no published reports refuted the findings. CONCLUSION: The evidence reviewed
      supports diabetes having an adverse effect on periodontal health and periodontal
      infection having an adverse effect on glycemic control and incidence of diabetes
      complications. Further rigorous study is necessary to establish unequivocally
      that treating periodontal infections can contribute to glycemic control
      management and to the reduction of the burden of diabetes complications.

PMID- 18336371
TI  - Periodontal disease and diabetes.

PMID- 18336372
TI  - Molecular identification of bacteria on the tongue dorsum of subjects with and
      without halitosis.
AB  - AIM: Compare the microbial profiles on the tongue dorsum in patients with
      halitosis and control subjects in a UK population using culture-independent
      techniques. MATERIALS AND METHODS: Halitosis patients were screened according to
      our recently developed recruitment protocol. Scrapings from the tongue dorsum
      were obtained for 12 control subjects and 20 halitosis patients. Bacteria were
      identified by PCR amplification, cloning and sequencing of 16S rRNA genes.
      RESULTS: The predominant species found in the control samples were Lysobacter
      type species, Streptococcus salivarius, Veillonella dispar, unidentified oral
      bacterium, Actinomyces odontolyticus, Atopobium parvulum and Veillonella atypica.
      In the halitosis samples, Lysobacter-type species, S. salivarius, Prevotella
      melaninogenica, unidentified oral bacterium, Prevotella veroralis and Prevotella
      pallens were the most commonly found species. For the control samples, 13-16 (4.7
      5.8%) of 276 clones represented uncultured species, whereas in the halitosis
      samples, this proportion increased to 6.5-9.6% (36-53 of 553 clones). In the
      control samples, 22 (8.0%) of 276 clones represented potentially novel
      phylotypes, and in the halitosis samples, this figure was 39 (7.1%) of 553
      clones. CONCLUSIONS: The microflora associated with the tongue dorsum is complex
      in both the control and halitosis groups, but several key species predominate in
      both groups.

PMID- 18336373
TI  - Immunohistochemical study of fibroblasts and mast cells in chronic submandibular
      sialadenitis.
AB  - AIM: To further our understanding of the processes involved in fibrosis that
      occurs in chronic submandibular sialadenitis by investigating the distribution of
      myofibroblasts, CD34-positive fibroblasts and tryptase-containing mast cells.
      MATERIALS AND METHODS: Thirty specimens of chronic submandibular sialadenitis
      with varying degrees of fibrosis and five normal submandibular glands were
      examined immunohistochemically for the presence of CD34, alpha-smooth-muscle
      actin, desmin and tryptase. RESULTS: Myofibroblasts were not demonstrated by the
      techniques for alpha-smooth-muscle-actin or desmin. CD34-positive fibroblasts
      were found around normal and moderately atrophic acini, but were not found around
      extremely atrophic acini and duct-like structures or in periductal and
      interlobular fibrous tissue. Tryptase-containing mast cells were found around
      vessels in normal submandibular glands. They were found in increased numbers in
      chronic submandibular sialadenitis, particularly in glands with widespread
      fibrosis, in which they were found in the fibrous tissue, and in which the
      increase was statistically significant. CONCLUSIONS: The results of this
      investigation suggest that tryptase-containing mast cells are likely to be
      involved in the fibrosis of chronic submandibular sialadenitis, but
      myofibroblasts and CD34-positive fibroblasts are not.

PMID- 18336374
TI  - Clinical oral malodor measurement with a portable sulfide monitor.
AB  - OBJECTIVE: The aim of this study was to evaluate the clinical ability of
      Breathtron by comparing it with other malodor measurement procedures: the
      organoleptic test (OT) and gas chromatography (GC). SUBJECTS AND METHODS:
      Patients were 475 patients who visited a fresh breath clinic. Oral malodor was
      measured with the OT, GC, and Breathtron. Correlation analysis and two linear
      regression analyses were conducted to examine the relationship of the Breathtron
      values with OT scores and volatile sulfide compound (VSC) concentrations by GC:
      i.e. the regression of Breathtron on OT and the regression of Breathtron on total
      VSCs by GC. Receiver operating characteristics (ROC) analysis was conducted to
      investigate the sensitivity and specificity of Breathtron. RESULTS: The
      Breathtron values were significantly correlated with OT and VSCs by GC. In the
      regression analysis, predicted Breathtron values were 199.3 and 520.1 ppb for OT
      scores 1 and 2, and reasonably close to total VSCs by GC between 550 and 750 ppb.
      The ROC analysis demonstrated that Breathtron is a useful and valuable adjunct
      measurement tool. CONCLUSIONS: Breathtron is a simple, rapid and reliable
      appliance for screening oral malodor if an appropriate malodor threshold level is
      chosen.

PMID- 18336375
TI  - Updates on bisphosphonates and potential pathobiology of bisphosphonate-induced
      jaw osteonecrosis.
AB  - Osteonecrosis of the jaws is a major complication associated with long-term use
      of bisphosphonates. While osteonecrosis can arise from other precipitating
      conditions, bisphosphonate-induced jaw osteonecrosis (BJON) is highly associated
      with long-term administration of pamidronate (Aredia) and zoledronic acid
      (Zometa), which are two intravenous bisphosphonate formulations. The underlying
      pathogenesis of BJON and its site-specific presentation still remain to be fully
      elucidated. This review will discuss clinically available bisphosphonates,
      current opinions, pathogenesis, and management guidelines for bisphosphonate
      induced jaw osteonecrosis.

PMID- 18336377
TI  - Challenging times in a challenging world.

PMID- 18336378
TI  - The revisit of 2004 tsunami in Thailand: characteristics of wounds.
AB  - The name, tsunami that was unknown to most Thai people, had hit west southern
      coast of Thailand on 26 December 2004. Following the disaster, prices have been
      paid and many lessons have been learnt. The current report provides a historical
      background of the incident, which was reviewed by documents, brief discussion and
      observation. Data of the patients from three hospitals involved in the management
      were collected and reviewed. Some of the illustrations were from the operating
      rooms of Takuapa, Surat Thani and Songklanagarind hospitals. There were totally
      2311 patients. Of these, 45% were males and 40% were multinationals. Nearly 40%
      suffered from salted water aspiration, while 2% developed complication associated
      with near drowning. The most common orthopaedic-related injury were minor [559
      patients (24%)] and major wounds [586 (25%)]. Around 7% sustained fracture
      dislocation. Lower extremity fractures were more common. The characteristics of
      wounds associated with the tsunami were severe contamination, multiple sites and
      organ involvement. Another characteristic was the early development and spreading
      of infection. The lessons proposed by the study are that minor wound should be
      left open, small penetrating wound should be thoroughly explored and observed and
      lacerated wounds need emergency dressing, debridement and subsequent cleansing
      procedures. Re-evaluation and closed surveillance of the seriously injured
      patients are mandatory to eliminate the complicated infection and life
      threatening conditions. Medical record of any disastrous event should be
      completed by health care professionals. The model and reporting system should be
      internationalised.

PMID- 18336379
TI  - Vacuum-assisted closure of a large palmar defect after debriding a midpalmar
      tuberculous abscess.
AB  - A rare case of tuberculous deep palmar abscess of the hand was treated with
      radical excisional debridement, resulting in a large palmar skin and soft tissue
      defect that was successfully closed with a vacuum dressing followed by split skin
      grafting. Vacuum dressings are useful adjuncts to treat large soft tissue defects
      in patients who are unsuitable for complex reconstruction. The moist wound
      environment prevents desiccation of exposed vital structures and decreases pain,
      allowing early mobilisation in the hand. The wound granulates and contracts
      rapidly, allowing earlier skin grafting or faster healing by secondary intention.
      The closed system vacuum dressing is particularly useful in managing debrided
      tuberculous soft tissue infections. The dressing is perfectly sealed and requires
      less frequent changing, decreasing contamination and transmission of tuberculosis
      to other patients and health care staff, while minimising the risk of secondary
      nosocomial bacterial infection of the wound.

PMID- 18336380
TI  - Prospective clinical study of a new adhesive gelling foam dressing in pressure
      ulcers.
AB  - This prospective, non comparative study evaluated the safety and effectiveness of
      an adhesive gelling foam dressing in pressure ulcer management. Twenty-three
      subjects with exuding pressure ulcers were recruited from seven centres in the
      USA and Canada. Study treatment included an adhesive gelling foam dressing,
      optional tape/roll bandaging and mandatory pressure-reducing/relieving devices.
      Subjects were followed until ulcer healing, for up to 28 days, or on patient
      withdrawal from the study, whichever came first. Dressings were changed at least
      once every 7 days. Mean percentage change in ulcer area from baseline to final
      measurement was -13%. Investigators reported healing or subjective improvement of
      ulcer condition in 61% of patients. Mean dressing wear time was 4.2 days.
      Subjects found the dressing was comfortable, soothing and cushioning in situ at
      80%, 64% and 70% of dressing changes, respectively. Subjects reported pain
      severity of none or mild for every dressing change. Fourteen subjects experienced
      adverse events, including seven subjects with study-related maceration, erythema,
      wound enlargement, blister or infection. A regimen including an adhesive gelling
      foam dressing proved to be safe and effective for managing exudate, protecting
      the surrounding skin, minimising pain and supporting healing of pressure ulcers
      with exudate.

PMID- 18336381
TI  - Induction of MMP-1, MMP-3 and TIMP-1 in normal dermal fibroblasts by chronic
      venous leg ulcer wound fluid*.
AB  - In the wound bed of chronic venous leg ulcers, an imbalance of matrix
      metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may
      cause excessive proteolysis and impair wound granulation. Soluble mediators in
      the wound environment may be responsible for this imbalance. The in vitro effect
      of wound fluid from venous leg ulcers on dermal fibroblast production of MMP-1,
      MMP-3 and TIMP-1 was compared with the effect of acute wound fluid from two
      different sources: fluid from post-mastectomy axillary drains and fluid from skin
      graft donor sites. Significantly higher MMP-1 and MMP-3 levels were induced by
      chronic venous leg ulcer wound fluid compared with both types of acute wound
      fluid (P < 0.005). Chronic venous ulcer wound fluid reduced TIMP-1 protein levels
      significantly more than acute graft fluid (P < 0.05). Venous ulcer wound fluid
      significantly increased MMP-1 and MMP-3 production in dermal fibroblasts and
      reduced TIMP-1 production, confirming that mediators in the leg ulcer
      microenvironment can potentially induce excessive proteolysis in the ulcer dermis
      by altering the balance between MMPs and TIMPs. Inflammatory mediators including
      interleukin-1beta and tumour necrosis factor-alpha can induce these MMPs. Further
      work is required to confirm the factors responsible for the induction of a high
      MMP and low TIMP profile in fibroblasts by venous ulcer wound fluid.

PMID- 18336382
TI  - Laser in the treatment of hypertrophic burn scars.
AB  - This prospective study looked at the outcome of laser (light amplification by
      stimulated emission of radiation) treatment for hypertrophic scarring. Dermatrade
      mark K laser (a set of combined lasers erbium:yttrium aluminium garnet/carbon
      dioxide, qualified as a class IV laser) was used. Between 21 June 2000 and 19
      November 2002, at the Siemianowice Burn Center, Poland, 592 interventions, using
      laser, were performed on N= 327 patients (220 women and 107 men, aged between 3
      and 80 years). The majority of cases [N= 223 (68.9%)] were patients with post
      burn hypertrophic scars, and 104 cases (31.8%) had various types of hypertrophic
      scars. Evaluation took place using an adapted Vancouver Scar Scale and digital
      photographs as well as the patient's opinion. It was noted that after laser
      treatment, satisfactory results were achieved in 72% of cases. The scars had
      become less red (192/327 scored no redness at the end of the study versus 92/327
      upon initial), less raised (272/327 scored a flat scar versus 72/327 upon
      initial) and demonstrated an improved viscoelasticity (192/327 scored a soft skin
      versus 62/327 upon initial). Laser treatment did not improve contractures in post
      burn hypertrophic scars. Results were not confirmed using objective measurement
      tools, as these were not available to us.

PMID- 18336383
TI  - Uropathogenic Escherichia coli (UPEC) strains may carry virulence properties of
      diarrhoeagenic E. coli.
AB  - To analyze whether Escherichia coli strains that cause urinary tract infections
      (UPEC) share virulence characteristics with the diarrheagenic E. coli (DEC)
      pathotypes and to recognize their genetic diversity, 225 UPEC strains were
      examined for the presence of various properties of DEC and UPEC (type of
      interaction with HeLa cells, serogroups and presence of 30 virulence genes). No
      correlation between adherence patterns and serogroups was observed. Forty-five
      serogroups were found, but 64% of the strains belonged to one of the 12
      serogroups (O1, O2, O4, O6, O7, O14, O15, O18, O21, O25, O75, and O175) and
      carried UPEC virulence genes (pap, hly, aer, sfa, cnf). The DEC genes found were:
      aap, aatA, aggC, agg3C, aggR, astA, eae, ehly, iha, irp2, lpfA(O113), pet, pic,
      pilS, and shf. Sixteen strains presented aggregative adherence and/or the aatA
      sequence, which are characteristics of enteroaggregative E. coli (EAEC), one of
      the DEC pathotypes. In summary, certain UPEC strains may carry DEC virulence
      properties, mostly associated to the EAEC pathotype. This finding raises the
      possibility that at least some faecal EAEC strains might represent potential
      uropathogens. Alternatively, certain UPEC strains may have acquired EAEC
      properties, becoming a potential cause of diarrhoea.

PMID- 18336384
TI  - Cryptococcus neoformans activates bone marrow-derived conventional dendritic
      cells rather than plasmacytoid dendritic cells and down-regulates macrophages.
AB  - Induction of IL-12 and IL-23 is essential for protective immunity against
      Cryptococcusneoformans. The contribution of dendritic cells vs. macrophages to IL
      12/23 production in response to C. neoformans infection is unclear. Activation of
      conventional bone marrow-derived dendritic cells (BMDC), plasmacytoid BMDC, and
      bone marrow-derived macrophages (BMMPhi) was assessed by analyzing cytokine
      responses and the expression of MHC-II, CD86, and CD80 in each cell type.
      Cryptococcus neoformans induced the release of IL-12/23p40 by BMDC, but not by
      BMMPhi, in a TLR2- and TLR4-independent but MyD88-dependent manner. Conventional
      BMDC rather than plasmacytoid BMDC up-regulated MHC-II and CD86, while BMMPhi
      down-regulated MHC-II and CD86 in response to C. neoformans. The up-regulation of
      MHC-II and CD86 on BMDC required MyD88. Our data point to conventional DC as
      critical IL-12/23-producing antigen-presenting cells during cryptococcosis.

PMID- 18336385
TI  - Immunological factors in pregnancy wastage: fact or fiction.
AB  - Whether maternal immune effector mechanisms with the exception of anti
      phospholipid antibodies cause pregnancy loss, and whether effective treatment is
      possible are subjects of controversy. Hence, in this study the current literature
      was searched and critically reviewed. In both animals and humans, similar immune
      effector mechanisms are linked to pregnancy failure. Several levels of evidence
      indicate that treatments such as aspirin + heparin, intravenous immunoglobulins,
      corticosteroids, and transfer of allogeneic blood cells bearing paternal antigens
      may improve the live birth rate. Combination therapy appears promising, but
      better diagnosis of subgroups responsive to specific therapies is critical. There
      are fallacies and flaws in the logic of previous arguments against immunological
      mechanisms and therapeutic interventions. In order to select patients most likely
      to benefit from known treatments, more extensive immunological testing is
      required. It is also important to determine the karyotype of all failing embryos.

PMID- 18336386
TI  - Immune regulation at the interface during early steps of murine implantation:
      involvement of two new cytokines of the IL-12 family (IL-23 and IL-27) and of
      TWEAK.
AB  - PROBLEM: An important subset of implantation defects/early abortion seems to be
      linked with a deregulation of the interleukin (IL)-12/IL-15/IL-18 system as well
      as tumor necrosis factor (TNF)- and natural killer (NK)-controlled/mediated
      networks at the decidual placental interface, both in case of deficient or excess
      expression. The presence of TNF in high amounts in the pre/peri-implantation
      uterus and its pivotal role during pregnancy are difficult to reconcile with its
      abortive effects in ongoing pregnancy. We therefore searched for regulators of
      the IL-12/IL-18 family of cytokines as well as for antagonist(s) of TNF with
      potentially selective effects on implantation. METHOD OF STUDY: We first used
      Swiss mice to verify the presence in the murine reproductive tract of 'new
      members' of the IL-12 family of cytokines, IL-23 and IL-27, as well as of tumor
      necrosis factor-like WEAK inducer of apoptosis (TWEAK), described as acting with
      TNF as Yin and Yang of innate immunity in murine placenta/ decidua at days 0
      12.5. We then compared expression by RT-PCR in the CBA x DBA/2, and CBA x BALB/c
      murine mating combinations. Finally, we performed in vivo neutralization
      experiments of TWEAK and IL-27. RESULTS: Immunohistochemistry (IHC) studies
      showed that IL-23, IL-27, and TWEAK were expressed at the interface. For RT-PCR,
      IL-23 expression peaked at day 9.5 in the non-aborting mating combination, a peak
      absent in the aborting one, and thus difficult to explain except by invoking a
      feed back on EB13 (Epstein-Barr virus-induced gene 3 cytokine). Most important,
      an immediate post-mating IL-27 hyper expression was seen in the CBA x DBA/2
      mating compared to CBA x BALB/c one. The difference in expression resurged and
      was statistically very significant by days 6.5-9.5, compatible with an early
      activation of inflammation on day 0.5 which would then peak again in the
      'resorption window' where takes place the early NK/mph activation described by
      Baines et al. A significant TWEAK expression was present in both strains from
      days 0.5 to 4.5 peaking in both cases in the first days when it is known that
      intra uterine TNF also reaches high levels as a component of post-mating
      inflammation. However, it was lower from day 1.5 in the abortion-prone CBA x
      DBA/2 mating combination, and almost absent by days 6.5-9.5 when compared to the
      non-aborting CBA x BALB/c mating combination. In both mating combinations,
      neutralization of TWEAK-enhanced resorption rates, but surprisingly so did IL-27
      neutralization. CONCLUSION: TWEAK is likely offering protection against the
      deleterious effects of TNF in implantation explaining embryo survival in a TNF
      rich environment, and equal number of implants in both strains. However, there is
      a clear difference of protection in abortion-prone mating peaking in the
      abortion/resorption window but starting early, and therefore possible links with
      the prevention of abortion in CBA x DBA/2 matings by interfering with complement
      activation as recently described by Girardi et al. are discussed, as well as
      consequences for our current view of feto-maternal 'seed and soil' interplay. The
      apparently paradoxical effects of IL-27 neutralization are also discussed.

PMID- 18336387
TI  - Role of mu-calpain in human decidua for recurrent miscarriage.
AB  - PROBLEM: Earlier, we showed that calpain activated by increasing intracellular
      calcium ion concentration in endometrial cells, causes endometrial dysfunction
      for implantation and early pregnancy. In the present study, we investigated the
      existence and distribution of calpains, calpastatin, integrin beta3 and alpha
      fodrin in decidua from patients with recurrent miscarriage. METHOD OF STUDY:
      Deciduae were surgically collected from 29 patients with recurrent miscarriage
      and 20 healthy women with informed consent. Immunohistochemistry, sodium dodecyl
      sulphate-polyacrylamide gel electrophoresis, and western blot analysis were
      performed. RESULTS: Staining of mu-calpain, m-calpain, calpastatin, integrin
      beta3 and alpha-fodrin were observed in the cytoplasm of stromal and epithelial
      cells in decidua using immunohistochemistry. No significant differences were
      observed in staining patterns. Western blot analysis showed no significant
      differences in expression of m-calpain, calpastatin and alpha-fodrin, whereas mu
      calpain was significantly higher and integrin beta3 was lower in subject.
      CONCLUSION: The results suggest that cleavage of integrin beta3 by mu-calpain may
      have an adverse effect on the mechanism of early pregnancy.

PMID- 18336388
TI  - Interleukin 6-174 G/C promoter polymorphism and pregnancy complications: results
      of a prospective cohort study in 1626 pregnant women.
AB  - PROBLEM: To investigate the frequency of the interleukin-6 (IL-6) -174 G/C single
      nucleotide polymorphism (SNP) in women with intrauterine fetal death (IUFD), pre
      eclampsia (PE), preterm delivery (PD), and small for gestational age (SGA)
      infants. METHOD OF STUDY: In a prospective cohort study, DNA from 1626
      consecutive pregnant women was analyzed for IL-6 -174 G/C. Women who developed at
      least one of the predefined pregnancy complications were used as cases and
      compared with women without pregnancy complications. RESULTS: Of 1626 women, 259
      (15.9%) developed at least one pregnancy complication. IL-6 -174 G/C allele
      frequencies and genotype distributions were not significantly different between
      cases and controls. Similarly, no statistically significant difference in IL-6 
      174 G/C genotype distribution in women with IUFD, PE, PD <34 weeks, PD >34 weeks
      and SGA infants <10th percentile was observed. CONCLUSION: IL-6 -174 G/C is not a
      genetic marker for identifying women at increased risk of common pregnancy
      complications.

PMID- 18336389
TI  - Th1 and Th2 in human IVF pregnancy with allogenic fetus.
AB  - PROBLEM: Positive obstetric outcome of allogenic in vitro fertilization (IVF)
      pregnancies makes interesting the subject of additional regulatory mechanisms
      after oocyte donation. METHOD OF STUDY: Eighty eight women: 23 donation of
      oocytes (DO), 33 IVF, 32 natural conception (NC) were studied in first trimester
      of pregnancy. Intracellular production of cytokines and chemokine receptors
      expression were studied by flow cytometry. RESULTS: Intracellular production of
      interferon-gamma (IFN-gamma), interleukin (IL)-4, tumor necrosis factor-alpha by
      CD4 T lymphocytes in DO women was higher than in IVF and NC women. Ratio IFN
      gamma/IL-4 in DO was lower than in IVF. We found higher expression of chemokine
      receptor CCR4 but not CXCR3 on CD4 T cells in DO compared with IVF and NC. Ratio
      CXCR3/CCR4 in DO was lower than in NC. CONCLUSION: Hyperactivation of T helper 1
      (Th1) and T helper 2 (Th2) by allogenic fetus is specific for DO pregnancy.
      Preferable activation of Th2 and relative suppression of Th1 chemokine expression
      reflect additional regulatory counteractive mechanism(s).

PMID- 18336390
TI  - Superficial implantation in pigs is associated with decreased numbers and
      redistribution of endometrial NK-cell populations.
AB  - PROBLEM: We evaluated implantation-associated quantitative changes in endometrial
      and peripheral natural killer (NK)-cell populations of pigs. METHOD OF STUDY:
      Natural killer cell populations were investigated in 10, 15, 20, 30 and 40 days
      pregnant and non-pregnant (NP) sows by flow cytometry, immunohistochemistry and
      morphometry. RESULTS: The number of endometrial CD16(+) NK cells significantly
      declined at attachment phase of implantation and remained relatively low over the
      course of implantation. The CD16(+) NK cells in situ showed implantation-phase
      dependent density and localization. Prior to implantation, they substantially
      resided in the subepithelial stroma. As implantation advances, the density of NK
      cells into subepithelial stroma decreased while that of NK cells into glandular
      layer increased, suggesting implantation-induced re-location far from the
      attached conceptus. The number of CD56(+) lymphocytes was the greatest at pre
      attachment phase of implantation, dropped at the time of attachment and increased
      up to end of early pregnancy period. The CD3(-) CD8(+) NK-cell number decreased
      significantly when the definitive placenta is established. No significant
      differences in the numbers of peripheral blood CD16(+), CD56(+) and CD3(-) CD8(+)
      NK cells between pregnant and NP animals as well as relative to the implantation
      phase were observed. CONCLUSION: Superficial and adeciduate implantation of pigs
      is associated with decreased numbers of endometrial NK-cell populations and
      specific spatiotemporal profile of classical NK cells.

PMID- 18336391
TI  - Ovarian cancer in the proteomics era.
AB  - Ovarian cancer presents a diagnostic challenge because of its subtle clinical
      presentation and elusive cell of origin. Two new technologies of proteomics have
      advanced the dissection of the underlying molecular signaling events and the
      proteomic characterization of ovarian cancer: mass spectrometry and protein array
      analysis. Mass spectrometry can provide a snapshot of a proteome in time and
      space, with sensitivity and resolution that may allow identification of the
      elusive "needle in the haystack" heralding ovarian cancer. Proteomic profiling of
      tumor tissue samples can survey molecular targets during treatment and quantify
      changes using reverse phase protein arrays generated from tumor samples captured
      by microdissection, lysed and spotted in serial dilutions for high-throughput
      analysis. This approach can be applied to identify the optimal biological dose of
      a targeted agent and to validate target to outcome link. The evolution of
      proteomic technologies has the capacity to advance rapidly our understanding of
      ovarian cancer at a molecular level and thus elucidate new directions for the
      treatment of this disease.

PMID- 18336392
TI  - Management of retroperitoneal lymph nodes in advanced ovarian cancer.
AB  - Autopsy studies have demonstrated a very high incidence of positive
      retroperitoneal lymph nodes in patients with advanced ovarian cancer, but the
      clinical management of these nodes has only recently been investigated. Several
      institutional studies had suggested an advantage to systematic removal of pelvic
      and paraaortic nodes in patients whose tumor was optimally cytoreduced in the
      peritoneal cavity. However, the only randomized prospective study revealed a 7
      month benefit in progression-free survival for patients having systematic
      lymphadenectomy, but no benefit in terms of overall survival. Unless a future
      randomized trial shows evidence to the contrary, removal of clinically normal
      nodes should not be considered part of the standard care for patients with
      advanced ovarian cancer. Bulky nodes should be removed as part of the surgical
      aim of removing all macroscopic residual disease.

PMID- 18336393
TI  - Timing of debulking surgery in advanced ovarian cancer.
AB  - It is clear that primary debulking remains the standard of care within the
      treatment of advanced ovarian cancer (FIGO stage III and IV). This debulking
      surgery should be performed by a gynecological oncologist without any residual
      tumor load, or so-called "optimal debulking." Over the last decades, interest in
      the use of neoadjuvant chemotherapy together with an interval debulking has
      increased. Neoadjuvant therapy can be used for patients who are primarily
      suboptimally debulked due to an extensive tumor load. In this situation, based on
      the randomized European Organization for Research and Treatment of Cancer
      Gynaecological Cancer Group trial, interval debulking by an experienced surgeon
      improves survival in some patients who did not undergo optimal primary debulking
      surgery. Based on the GOG 152 data, interval debulking surgery does not seem to
      be indicated in patients who underwent primarily a maximal surgical effort by a
      gynecological oncologist. Neoadjuvant chemotherapy can also be used as an
      alternative to primary debulking. In retrospective analyses, neoadjuvant
      chemotherapy followed by interval debulking surgery does not seem to worsen
      prognosis compared to primary debulking surgery followed by chemotherapy.
      However, we will have to wait for the results of future randomized trials to know
      whether neoadjuvant chemotherapy followed by interval debulking surgery is a good
      alternative to primary debulking surgery in stage IIIc and IV patients. Open
      laparoscopy is probably the most valuable tool for evaluating the operability
      primarily or at the time of interval debulking surgery.

PMID- 18336394
TI  - Pharmacologic principles of intraperitoneal chemotherapy for the treatment of
      ovarian cancer.
AB  - Intraperitoneal therapy has now been demonstrated in multiple randomized trials
      to improve the outcome of chemotherapy for patients with optimally debulked or
      small volume ovarian carcinoma. This article reviews the basic pharmacologic
      principles that underlie the use of intraperitoneal therapy and identifies the
      key factors that determine the pharmacologic advantage of this route of
      administration. These include the relative peritoneal and plasma clearances and
      elements of tumor vascular permeability and blood flow that limit the penetration
      of drug entering tumor nodules by free-surface diffusion. New information about
      how cisplatin and carboplatin are transported into ovarian carcinoma cells points
      to novel strategies for further improving the therapeutic effectiveness of
      intraperitoneal chemotherapy.

PMID- 18336395
TI  - National Cancer Institute-United States strategy regarding intraperitoneal
      chemotherapy for ovarian cancer.
AB  - On the basis of three large randomized phase III trials, the National Cancer
      Institute (NCI) issued a Clinical Announcement in January 2006 recommending that
      women with optimally debulked stage III ovarian cancer and their physicians
      consider a combination of intravenous (IV) and intraperitoneal (IP) chemotherapy.
      The combination of IV and IP chemotherapy is associated with a clinically
      significant benefit in survival, although it does also confer an increased risk
      of toxicity compared to IV chemotherapy alone. The NCI Clinical Announcement was
      issued as part of a broader educational campaign, designed in conjunction with
      professional societies, cancer centers, Clinical Trials Cooperative Groups, and
      cancer advocacy organizations. The further development of IP chemotherapy in
      ovarian cancer requires additional clinical and translational research.

PMID- 18336396
TI  - Can carboplatin replace cisplatin for intraperitoneal use?
AB  - Intraperitoneal (IP) chemotherapy is theoretically a feasible route for treating
      ovarian cancer. It is possible to expose tumor tissue disseminated peritoneal
      surface to extremely high concentration of anticancer agents. Three large-scale,
      randomized trials conducted in the US have demonstrated a significant improvement
      of progression survival and/or overall survival in IP chemotherapy arm over
      intravenous arm. Despite these favorable results, IP chemotherapy has not been
      accepted as standard care. One of the reasons for this is the use of cisplatin,
      which has been replaced by the less toxic platinum agent, carboplatin, when
      administered intravenously. In this review article, we discuss why IP
      chemotherapy using carboplatin has been ignored and its future potential.

PMID- 18336397
TI  - Strategies to examine new compounds for intraperitoneal use in ovarian cancer.
AB  - The results of three large well-designed randomized trials demonstrating the
      favorable impact of primary cisplatin-based chemotherapy on survival in small
      volume residual advanced ovarian cancer has stimulated considerable interest in
      exploration of this route of drug delivery for other antineoplastic agents. A
      number of relevant properties of both the drugs and the peritoneal cavity need to
      be considered in preclinical evaluation such that future clinical development
      will focus on strategies that have a realistic potential for being safe and
      effective when they enter the clinical arena.

PMID- 18336398
TI  - What is the optimal approach to the administration of intraperitoneal
      chemotherapy in ovarian cancer?
AB  - Three well-designed and conducted randomized phase 3 trials have revealed that
      the intraperitoneal administration of cisplatin-based chemotherapy as primary
      treatment of small-volume residual advanced ovarian cancer improves both
      progression-free and overall survivals compared to an all intravenous cisplatin
      based regimen. Based on very reasonable extrapolations from existing evidence
      based data, a number of possible "options" can be proposed that use the
      intraperitoneal route for delivery of chemotherapy in this clinical setting.

PMID- 18336399
TI  - Maintenance chemotherapy in advanced ovarian cancer: the US experience.
AB  - The somewhat controversial results of a Southwest Oncology Group/Gynecologic
      Oncology Group phase 3 randomized trial have revealed that a maintenance strategy
      consisting of 12 cycles of single-agent paclitaxel (175 mg/m(2) over 3 h every 28
      days), delivered to women with advanced ovarian cancer who have achieved a
      clinically defined complete response to primary platinum-paclitaxel chemotherapy,
      significantly improves progression-free survival compared to delivery of three
      cycles of the same treatment regimen. While it is not possible to provide a
      definitive statement regarding the impact of this management approach on overall
      survival, in an exploratory analysis, patients who initiated this study with a
      baseline CA-125 level <or=10 units/mL and were treated with the 12-cycle
      maintenance program experienced a statistically significant improvement in
      survival. An ongoing Gynecologic Oncology Group trial in the United States will
      hopefully provide a definitive answer to the question of the impact of this novel
      strategy on outcome in ovarian cancer.

PMID- 18336400
TI  - Radiation therapy and biological compounds for consolidation therapy in advanced
      ovarian cancer.
AB  - Consolidation therapy is used in order to maximize the benefit of first-line
      therapy and to improve the progression-free and overall survival of patients. In
      women with advanced epithelial ovarian cancer, tested maintenance and
      consolidation strategies following first-line chemotherapy include high-dose
      chemotherapy, radiation therapy, intraperitoneal radionuclides including those
      linked to an antibody, and biological and immunologic agents. This review focuses
      on the current understanding of the benefit of radiation therapy and biological
      agents used as consolidation in women with advanced ovarian cancer. Whole
      abdominal radiation has given promising results only in the subgroup of patients
      with pathologic complete response. However, this treatment modality is associated
      with considerable intestinal toxicity. Single treatment with intraperitoneal
      radionuclides, either alone (32P) or in combination with an antibody (90Y
      muHMFG1) has not improved survival. Biological agents used for consolidation
      include, eg, alpha- and gamma-interferon, tanomastat, a matrix metalloprotease
      inhibitor and oregovomab, a murine antibody that targets CA125. Randomized trials
      with these agents have not demonstrated any significant improvement in the
      overall survival of ovarian cancer patients. Currently, two ongoing studies (GOG
      218, ICON7) are examining the potential of bevacizumab in the maintenance therapy
      of advanced epithelial ovarian cancer. Evaluation of new agents is indicated in
      order to achieve long-term disease-free survival in these patients. Toxicity and
      ease of administration must be reflected against the benefits of therapy.

PMID- 18336401
TI  - First-line randomized trials: revisiting the Ptolemaic universe.
AB  - Epithelial ovarian cancer is initially a chemosensitive neoplasm, with overall
      response rates to systemic platinum-based therapy exceeding 80% in conjunction
      with cytoreductive surgery. However, long-term survival remains poor due to
      eventual tumor recurrence and emergence of drug resistance. While platinum
      (cisplatin or carboplatin) and taxanes remain at the core of primary treatment,
      there has been increased interest in the evaluation of doublet and triplet
      combinations with diverse cytotoxic agents, including docetaxel, topotecan,
      gemcitabine, and PEG-liposomal doxorubicin. This has been prompted by single
      agent activity in the setting of recurrent platinum-resistant disease and
      encouraging data from nonrandomized phase I-II trials. As a result, beginning in
      1998, the international cooperative groups collaborated on a series of phase III
      trials to improve long-term outcomes through the development of new platinum
      based combinations. More than 10,000 women have been randomized on these trials,
      and preliminary data from several studies have been reported. Although final data
      are pending, there is not currently any evidence to recommend adopting a new two-
      or three-drug combination, and carboplatin with paclitaxel remains the standard
      regimen of choice. Rapid developments in molecular-targeted therapy are
      challenging our paradigm for future clinical trials, and our priorities need to
      be carefully considered.

PMID- 18336402
TI  - Lessons learned from a decade of clinical trials of high-dose chemotherapy in
      ovarian cancer.
AB  - Ovarian cancer is one of the most chemosensitive solid tumors and therefore a
      good example to explore high-dose chemotherapy (HDC). Interest in pursuing this
      treatment arose in the late 1980s following the success of HDC in treating
      hematological cancers and improvements in supportive care with peripheral blood
      stem cells. Experience from phase II trials and analysis of Bone Marrow
      Transplant Registry data led to the launch of several randomized phase III trials
      in the late 1990 s. Initial enthusiasm for this treatment was in part due to the
      preliminary positive data emerging from HDC in breast cancer. Five randomized
      trials of HDC in ovarian cancer have been conducted and all experienced
      difficulty in recruitment. Their different designs and results are reviewed, as
      well as some of the lessons that have been learned about HDC in solid tumors in
      the last decade.

PMID- 18336403
TI  - Second-line randomized trials in epithelial ovarian cancer.
AB  - Important issues in the treatment of patients with recurrent ovarian cancer (ROC)
      are 1) to delay the time to symptomatic disease, 2) to reduce symptoms in case of
      symptomatic disease, 3) to optimize quality of life, and 4) to prolong overall
      survival. However, response assessment and recording of treatment-induced side
      effects in general get most attention. The likelihood of response to chemotherapy
      is directly proportional to the length of time between the end of primary
      chemotherapy and the date of recurrence. Also, the aggressiveness of the
      recurrence seems related to the prior biological pace of disease progression. For
      these reasons different disease categories have been identified, ie,
      platinum/taxane-refractory disease (progressive during first-line stabilization
      as best response), persistent disease (partial response to first-line therapy),
      platinum/taxane-resistant disease (clinical complete response [CCR] or no
      evidence of disease [NED] to/after first line and relapse <6 months), and
      platinum/taxane-sensitive disease (CCR or NED to/after first line and relapse >6
      months). Randomized trials in these different categories did not show a benefit
      of maintenance or consolidation therapies after first-line therapy but did show
      differences in tolerability and efficacy (in platinum/taxane-sensitive disease)
      of different single agents and indicated that in specific circumstances
      combination chemotherapy is superior to single-agent chemotherapy. However, in
      all circumstances other aspects such as toxicity (and earlier experienced
      toxicity), clinical condition, convenience of administration, costs, and patient
      preference should be considered in the final selection of treatment.

PMID- 18336404
TI  - Ten years of "Optimal Therapy in Advanced Ovarian Cancer. Update" meeting.
AB  - The International Symposium on Advanced Ovarian Cancer: Optimal Therapy was
      founded by Dr. Andres Poveda and Prof. Jan B. Vermorken, and each edition has
      been directed by them. The 6th edition was held on March 2, 2007. This symposium
      is organized every other year by GEICO (Grupo Espanol de Investigacion de Cancer
      de Ovario/Spanish Ovarian Cancer Research Group), under the auspices of the
      Spanish Society of Medical Oncology (SEOM), the Gynecologic Cancer Intergroup
      (GCIG), and the European Society of Medical Oncology (ESMO) Educational Committee
      for its Medical Oncology Recertification Approval (ESMO/MORA) Program. One
      hundred and fifty people attended the symposium's 1st edition, held in 1996.
      Since then, the interest in this meeting has increased. Last year, almost three
      hundred people coming not only from Spain but also from Europe, North and Latin
      America, Asia, and Australia were present in the symposium. This is a great
      challenge for us. Some important international cooperative groups from Europe,
      America, and Australia collaborate with this symposium, such as GOG, NCIC, EORTC,
      AGO, Scottish Group, ICON, GINECO, NSGO, ANZGOG, and others.

PMID- 18336405
TI  - Future opportunities of the Gynecological Cancer Intergroup.
AB  - The Gynecologic Cancer Intergroup (GCIG) is an international collaboration of
      cooperative clinical trials groups who conduct randomized phase III clinical
      trials in the population of women affected by gynecologic cancer. This
      collaboration amongst 18 member groups allows for rapid accrual of women to such
      trials with outcomes that are rapidly generated and readily generalizable to a
      broad population. Future considerations should include studies in prevention and
      translational research through improved processes and new global partnerships.

PMID- 18336406
TI  - Addressing unanswered questions in ovarian cancer trial methodology: follow-up of
      the 2004 Baden-Baden Gynecologic Cancer Intergroup meeting.

PMID- 18336407
TI  - Metabolic response of the gastrointestinal tract and serum parameters of rabbits
      to diets containing chicory flour rich in inulin.
AB  - A 36-day experiment carried out on 54-day-old rabbits addressed the analysis of
      physiological properties of diets supplemented with chicory roots flour. Twenty
      four rabbits were allocated in individual cages to three treatments, in which
      they were fed each diet with the chicory flour at 0, 25 and 50 g/kg (control,
      ChF(2.5) and ChF(5) groups respectively). The chicory preparation administered at
      a higher dose, lowered ileal pH and viscosity, and evoked increased hydration of
      ileal and caecal digesta, compared to the control treatment (p </= 0.05). The
      ChF(2.5) group was characterized by the highest increase in the bulk of digesta
      and concentration of protein in the caecum (p < 0.05 vs. control). The lowest
      colonic pH was found in the ChF(5) group (p </= 0.05 vs. control). Compared to
      the control group, both chicory treatments effectively (p </= 0.05) diminished
      the activity of the potentially harmful bacterial enzymes beta-glucosidase and
      beta-glucuronidase in the caecal and colonic digesta. The ChF(2.5) group was
      characterized by a significantly higher volatile fatty acids (VFA) pool size in
      the caecum, whereas rabbits fed the ChF(5)diet had the highest colonic VFA pool
      size (p </= 0.05 vs. control). The lowest level of triglycerides and total
      cholesterol, at concurrently the highest proportion of high-density lipoprotein
      (HDL) fraction in the HDL/total cholesterol profile, were recorded in the plasma
      of rabbits fed the ChF(5) diet. In conclusion, the chicory flour rich in inulin,
      exerted positive effects on the rabbit gastrointestinal tract physiology and
      would be a potential source of functional feed additives.

PMID- 18336408
TI  - Effects of variety, cropping year, location and fertilizer application on
      nutritive value of durum wheat straw.
AB  - This study was carried out to assess the effects of variety, year, location and
      level of fertilizer application on chemical composition and in sacco dry matter
      (DM) degradability of durum wheat straw as well as to understand the relationship
      between straw quality and agronomic traits of the crop and to assess the
      possibilities of selecting wheat varieties that combine high grain yield with
      desirable straw quality. Two local (Arendeto and Tikur sinde) and two improved
      (Boohai and Gerardo) varieties of durum wheat (Triticum turgidum Desf.) were used
      in the experiment. The four varieties were grown at two locations (Akaki and
      Ejere) in the years 2001/2002 and 2002/2003 in 5 x 5 m plots in three
      replications. Diammonium phosphate and urea fertilizers were applied at four
      levels (0/0, 32/23, 41/23 and 64/46 kg/ha of nitrogen/phosphorus). Straw quality
      was assessed based on chemical composition and in sacco DM degradability.
      Correlation of straw quality with grain and straw yield and with other agronomic
      characteristics of the crop was determined. The potential utility index (a
      measure that integrates grain and digestible straw yield) was used for ranking of
      the varieties. The local varieties had higher crude protein (CP) and lower
      neutral detergent fibre contents and higher digestibility than the improved
      varieties. The cropping year and location had significant effect on CP content
      and degradability of the straw, which could be due to climatic variation.
      However, the fertilizer level did not have any significant effect on straw
      quality except that the CP content of the straw tended to increase with
      increasing level of fertilizer application. Based on the potential utility index
      the varieties ranked, in a decreasing order, as Tikur sinde > Arendeto > Gerardo
      > Boohai and the ranking was consistent across years and locations. Except the CP
      content, straw quality was not negatively correlated with grain and straw yield.
      This indicates that there is a possibility of selecting varieties of wheat that
      combine high grain and straw yield with desirable straw quality.

PMID- 18336409
TI  - Chromium nanoparticle exhibits higher absorption efficiency than chromium
      picolinate and chromium chloride in Caco-2 cell monolayers.
AB  - This study was conducted to determine whether chromium nanoparticle (CrNano)
      exhibited higher absorption efficiency and possessed unique absorption mechanism
      in comparison to chromium picolinate (CrPic) and chromium chloride (CrCl(3)), as
      was postulated by previous reports. Twenty-one-day-old Caco-2 cell monolayers
      grown on semipermeable membranes in Snapwell tissue culture bichambers were
      incubated with CrNano, CrPic or CrCl(3) to examine their transport and uptake
      respectively. In the concentration range of 0.2-20 micromol/l, transport of
      CrNano, CrPic and CrCl(3) across Caco-2 monolayers both in apical-to-basolateral
      and basolateral-to-apical direction was concentration-, and time-dependent, and
      temperature independent. The apparent permeability coefficient (P(app)) of CrNano
      was between 5.89 and 7.92 x 10(-6) cm/s and that of CrPic and CrCl(3) was between
      3.52 and 5.31 x 10(-6) cm/s and between 0.97 and 1.37 x 10(-6) cm/s respectively.
      Uptake of CrNano, CrPic and CrCl(3) by both apical and basolateral membranes was
      concentration- and time-dependent. Uptake of CrNano by apical membrane was
      significantly (p < 0.05) decreased when the incubation temperature was reduced
      from 37 degrees C to 4 degrees C. The transport efficiency of CrNano, CrPic and
      CrCl(3) after incubation for 120 min at 37 degrees C was 15.83% +/- 0.76%, 9.08%
      +/- 0.25% and 2.11% +/- 0.53% respectively. The uptake efficiency of CrNano,
      CrPic and CrCl(3) was 10.08% +/- 0.76%, 4.73% +/- 0.60% and 0.88% +/- 0.08%
      respectively. It was concluded that the epithelial transport of CrNano, CrPic and
      CrCl(3) across the Caco-2 cell monolayers was mainly via passive transport
      pathways. In addition, CrNano exhibited considerably higher absorption efficiency
      than both CrPic and CrCl(3) in Caco-2 cell monolayers.

PMID- 18336410
TI  - A comparative study of nutrients utilization, alkaline phosphatase activity and
      creatinine concentration in the serum of sheep and goats fed diets based on olive
      leaves.
AB  - The aim of this study was to compare, in goats and wethers, the nutritive
      utilization of diets including olive leaves (OL) and the possible detrimental
      effect of that by-product. Three different diets were studied: OL, OL plus
      polyethylene glycol (PEG) (OLP) and OL supplemented with barley [164 g/kg dry
      matter (DM)] and faba beans (59 g/kg DM) (OLSUP). Apparent digestibility of
      nutrients and energy and nitrogen balances were determined along with creatinine
      concentrations and alkaline phosphatase (ALP) activity in the serum. The apparent
      digestibility of OL was low and similar in goats and wethers (54.4% and 53.5%,
      22.2% and 21.6% and, 47.7% and 46.6% for DM, crude protein and neutral detergent
      fibre in goats and wethers, respectively). The addition of PEG did not improve (p
      > 0.05) digestibility of OL, although a slightly beneficial effect on the
      digestion of structural carbohydrates was observed (up to 8.4% and 7.10% in goats
      and wethers, respectively). The supplementation of OL with barley and faba beans
      increased (p < 0.001) the apparent digestibility of nutrients and the energy
      value. The consumption of the OL led to high ALP activity in the serum. Despite
      the higher sensitivity of wethers to Cu levels, our results show a similar
      digestive use of OL by wethers and goats and suggest the need of further
      comparative investigations focusing on the effect of the presence of high Cu
      levels in the by-product on the animal health.

PMID- 18336411
TI  - Dietary crude protein has minimal effect on the activity of selected enzymes of
      methionine catabolism in kittens fed diets near-limiting in methionine.
AB  - Previous experiments have shown that increasing the dietary crude protein (CP) of
      cats does not increase urea cycle enzymes or alanine amino transferase as occurs
      in rats. Also when an essential amino acid (EAA) is limiting in a diet for
      growing kittens, the kittens do not exhibit an amino acid imbalance when other
      EAAs are added to the diet. To study the metabolic basis for these observations
      which are different from that found in omnivores and herbivores, the hypothesis
      that increased dietary CP decreases methionine catabolism, so more is spared for
      growth, was tested. Fifteen male kittens were randomly assigned to one of three
      dietary treatments. Each diet contained 2.5 g l-methionine/kg diet and 200, 300
      or 500 g CP/kg diet. The livers and kidneys were removed and assayed for
      methionine transaminase (MTA), cystathionase (CASE) and cystathionine synthase
      (CS). Free amino acid concentrations were determined in liver, kidney and plasma.
      The 300 and 500 g CP/kg groups had significantly greater kidney weights and body
      weight gains than the 200 g CP/kg group. Hepatic MTA activity was lower in the
      300 than the 200 or 500 g CP/kg groups (p < 0.05). Renal MTA and CASE activities
      were 35% and 50% greater, respectively, for the 500 g CP/kg group than for the
      200 g CP/kg diet group (p < 0.05). Renal CS activities for the 300 and 500 g
      CP/kg groups were 29% (p > 0.05) and 38% (p < 0.05) greater, respectively, than
      the 200 g CP/kg group. Cyst(e)ine concentrations were lower in the livers of the
      500 g CP/kg group than the 200 g CP/kg group (p < 0.05). Cystathionine was lower
      in plasma and kidney from the 500 g CP/kg diet group than from the 200 g CP/kg
      diet group (p < 0.05). It was concluded that the metabolic basis for the
      increased growth of kittens fed diets marginally limiting in methionine, with
      increasing concentrations of dietary CP, was not mediated through decreased
      enzyme activity associated with the catabolism of methionine, but was the result
      of an increase in food (methionine) intake.

PMID- 18336412
TI  - Effects of maize grain and lucerne particle size on ruminal fermentation,
      digestibility and performance of cows in midlactation.
AB  - This study evaluated the effects of, and interactions between, maize grain
      particle size (MPS) and lucerne particle size (LPS) on dry matter intake, milk
      production, milk composition, ruminal fermentation, microbial yield, chewing
      activity and nutrient digestibility in midlactation cows. Four multiparous
      Holstein cows with ruminal cannulas were assigned randomly to a 4 x 4 Latin
      square design, averaged 595 kg (SD = 52) of body weight and 121 days in milk (SD
      = 21) at the start of the experiment. Experimental periods were 21 days in length
      (14 days of treatment adaptation and 7 days of data collection). All diets were
      fed as total mixed ration and were formulated to meet or exceed the requirements
      of a 600 kg multiparous cow producing 20 kg milk/day with 4.0% fat. The ratio of
      concentrate to forage was 39:61 (dry matter basis). Treatments were arranged in a
      2 x 2 factorial design; two levels of LPS (2.54 and 6.22 mm) were combined with
      concentrates based on either ground maize grain (711 mum) or cracked maize grain
      (1755 mum). Maize grain and LPS did not affect milk production and milk fat
      percentage. Milk protein percentage increased when MPS was decreased (p = 0.04).
      Milk urea nitrogen was lower for cows fed ground maize grain compared with
      cracked maize grain (118-134 mg/l, p = 0.05). Estimated microbial N supply
      increased 41.9 g/day for ground maize grain compared with cracked maize grain.
      Cows fed long lucerne (LL) hay spent more time ruminating compared with cows fed
      short lucerne (SL) hay ranging from 293 to 336 min/day (p < 0.001). Total time
      spent chewing by cows increased from 505 to 574 min/day (p = 0.002) for SL and LL
      respectively. Based on the results from this study, midlactation cows can be fed
      diets that contain ground maize grain and SL hay without leading to negative
      effects on ruminal pH and nutrient digestibility.

PMID- 18336413
TI  - Effects of ethylenediaminetetraacetic acid on phytate phosphorus utilization and
      efficiency of microbial phytase in broiler chicks.
AB  - Previous studies have suggested that organic acids may improve P utilization in
      animals. To evaluate the ability of ethylenediaminetetraacetic acid (EDTA) to
      improve phytate P utilization and the possible synergistic effect between EDTA
      and microbial phytase (MP) an experiment was conducted using 360 Ross 308 broiler
      chicks. The experiment was carried out using a completely randomized design with
      a 3*2 factorial arrangement (0, 0.1 and 0.2% EDTA and 0 and 500 IU MP). Four
      replicate of 15 chicks per each were fed dietary treatments including (i) P
      deficient basal diet [0.2% available phosphorus (aP)] (NC); (ii) NC + 500 IU MP
      per kilogram of diet; (iii) NC + 0.1% EDTA per kilogram of diet; (iv) NC + 0.1%
      EDTA and 500 IU MP per kilogram of diet; (v) NC + 0.2% EDTA per kilogram; and
      (vi) NC + 0.2% EDTA + 500 IU MP per kilogram of diet. Weight gain (WG), feed
      efficiency and serum Ca, P and alkaline phosphatase (ALP) were assessed. Addition
      of 0.2% EDTA to low aP diets resulted in significantly lower feed consumption
      (FC) and WG, but 0.1% EDTA did not depress WG compared to NC. Phytase
      supplementation of P-deficient diets significantly improved WG and feed
      efficiency, but it had no effect on FC. Microbial phytase supplementation
      significantly decreased ALP concentration. Results obtained in our study suggest
      no synergistic effect between phytase and EDTA in broiler chicks.

PMID- 18336414
TI  - Mineral balance in horses fed two supplemental silicon sources.
AB  - Numerous studies suggest that silicon (Si) supplementation is beneficial for
      mineral metabolism and bone health. Mineral balance studies have not been
      performed in horses to determine how these supplements affect absorption of other
      minerals. The purpose of these studies was to investigate the effects of two
      different Si supplements on mineral absorption and retention in horses. Eight
      geldings were randomly placed in one of two groups: control (CO) or supplemental
      Si, which was provided by one of two supplements. The first, sodium aluminium
      silicate (SA), contains a bioavailable form of Si and is high in aluminium (Al).
      The second supplement contains oligomeric orthosilicic acid (OSA). All horses
      received textured feed and ad libitum access to hay. Supplemented horses received
      either 200 g of SA or 28.6 ml of OSA per day. Following a 10-day adaptation
      period, the horses underwent a 3-day total collection. Blood samples were taken
      on days 0 and 13. The two balance studies were conducted 4 months apart to reduce
      carryover effects. Intakes of Al and Si were greater with SA supplementation (p <
      0.05). Sodium aluminium silicate increased faecal and urinary Si excretion (p <
      0.05). Calcium retention and apparent digestion were increased by SA (p < 0.05).
      It also maintained plasma Si compared with the CO which tended to have a decrease
      in plasma Si (p = 0.08). Supplemental OSA increased retention of Ca and B (p <
      0.05) and apparent digestion of B (p < 0.01). Orthosilicic acid tended to
      increase Si retention (p = 0.054), apparent digestion (p < 0.065), and also
      increased plasma Si. Both supplements were able to alter Ca retention and B
      metabolism, however, only OSA was able to alter Si retention, digestibility and
      plasma concentration. Orthosilicic acid, an Si supplement without substantial Al,
      appears to be a viable option for Si supplementation as it increased Si retention
      and digestibility.

PMID- 18336415
TI  - The absorption, tissue distribution and excretion of enteraly administered alpha
      ketoglutarate in rats.
AB  - The absorption, tissue distribution and excretion of enteral alpha-ketoglutarate
      (AKG) was studied in four experiments. Six male Sprague Dawley rats were used to
      investigate the excretion of AKG in urine and faeces. Thirty rats, randomly
      assigned to five groups, were used to investigate the distribution of AKG in body
      tissues. They were gavaged with AKG enriched with 3 muCi/kg BW of (14)C uniformly
      marked AKG. Fourteen male Sprague Dawley rats were used to study the absorption
      of AKG (duodenum vs. ileum). Intestinal recovery of NaAKG vs. CaAKG was
      investigated in 36 rats. There was no significant excretion of non-metabolized
      AKG in the urine and faeces. There was no significant difference in the systemic
      levels of AKG when comparing the proximal to distal small intestine infusion. Up
      to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach,
      0.5, 1 and 2 h after gavage; the jejunal recovery achieved a maximum of 3%, 30
      min after gavage, and was not detectable 2 h later. There was a relatively high
      distribution of (14)C-AKG in the tissues (e.g. liver, brain, bones, skin,
      muscles), 3 h after gavage, up to 70% of the administered dose. In conclusion,
      the high rate of retention of the carbon from AKG allows the postulation that
      there is a non-energetic mode of metabolism of intragastrically administered AKG.
      After conversion to final metabolites, AKG penetrates into all tissues and organs
      of rats, including the bone tissue. Intestinal absorption of AKG does not depend
      on the type of AKG salt administered.

PMID- 18336416
TI  - Effects of feeding yeast and propionibacteria to dairy cows on milk yield and
      components, and reproduction*.
AB  - To determine the effect of supplemental feeding of Diamond V-XP yeast (XPY) alone
      or in combination with propionibacteria strain P169 on milk production, milk
      components, body weight, days to first and second ovulation, plasma insulin, and
      plasma and milk glucose, 31 primiparous and multiparous (MP) Holstein cows were
      fed one of three dietary treatments between 2 weeks prepartum to 30 weeks
      postpartum: (i) control (n = 10), fed a corn silage-based total mixed ration
      (TMR); (ii) XPY (n = 11), fed control TMR plus XPY (at 56 g/head/day); and (iii)
      P169+XPY (n = 10), received control TMR plus XPY plus P169 (at 6 x 10(11)
      cfu/head/day). After parturition, daily milk weights were recorded, and milk
      samples were collected twice weekly for milk component analyses. Daily
      uncorrected milk, solids-corrected milk, and 4% fat-corrected milk production for
      MP cows fed P169+XPY was 9-16% greater than control MP cows, but these increases
      were only evident during mid lactation (9-30 weeks). The percentage of milk fat
      was 8-18% greater in control than XPY and P169+XPY groups. Milk lactose
      percentage in MP cows fed P169+XPY was 3-5% greater than in control and XPY MP
      cows. Primiparous and MP cows fed P169+XPY had 28-32% greater milk glucose levels
      than control and XPY-fed cows. Diurnal plasma glucose concentration was not
      affected by diet in MP cows. Plasma insulin levels in MP cows fed P169+XPY were
      30-34% greater than in other groups of MP cows. Milk glucose and plasma insulin
      responses to P169+XPY feeding suggest that P169+XPY might have enhanced
      gluconeogenesis and increased glucose uptake by the mammary gland in Holstein
      cows. Thus, a combined feed supplement of P169 and XPY may hold potential as a
      natural feed alternative to hormones and antibiotics to enhance lactational
      performance.

PMID- 18336417
TI  - The effect of dietary l-carnitine supplementation on pulmonary hypertension
      syndrome mortality in broilers exposed to low temperatures.
AB  - Oxidative stress is involved in the development of pulmonary hypertension
      syndrome (PHS) in broilers. l-Carnitine has an antiperoxidative effect and
      supplemental l-carnitine has been revealed to increase broiler heart weight. The
      present study was conducted to evaluate the effect of an addition of 100 mg/kg l
      carnitine to the basal diets on PHS mortality in cold-exposed broilers. Two
      hundred and forty mixed-sex broilers were equally assigned to three groups. The
      control group was reared in normal temperatures throughout the experiment.
      Starting on day 14 continuing until the end of the experiment, the other two
      groups were subjected to a step-down temperature programme (by lowering the
      temperature 1-2 degrees C per day down to 12-14 degrees C) with or without l
      carnitine added to the basal diets. Cold exposure increased the right/total
      ventricle ratio (RV/TV) and plasma malondialdehyde (MDA), reduced superoxide
      dismutase (SOD) and led to pulmonary vascular remodelling in birds without
      feeding additional l-carnitine. Supplemental l-carnitine reduced plasma MDA,
      increased SOD, inhibited remodelling and postponed the occurrence of PHS for 1
      week in cold-exposed broilers; nevertheless, it did not significantly influence
      the cumulative PHS mortality (p > 0.05). On days 24 and 32, birds fed
      supplemental l-carnitine had lower RV/TV and higher total ventricle/body weight
      (p < 0.05) but unchanged right ventricle/body weight ratios (p > 0.05) compared
      to their cold-exposed counterparts, indicating an increase in left ventricle
      weight. However, from day 39 on, their RV/TV ratios were suddenly increased (p <
      0.05). It was suggested that the l-carnitine-induced increase in left heart
      weight might partially account for the postponed occurrence of pulmonary
      hypertension in the early stage by elevating cardiac output, which might, in
      turn, lead to the resulting increase in pulmonary pressure. In view of its
      complex effects on cardiopulmonary haemodynamics, l-carnitine supplementation may
      be impractical for reducing PHS.

PMID- 18336418
TI  - Dietary nucleotides protect thymocyte DNA from damage induced by cyclophosphamide
      in mice.
AB  - The effects of dietary nucleotides on thymocyte DNA damages induced by
      cyclophosphamide (CP) in mice were examined. First, phase I experiment was
      conducted to determine the optimal timing of detecting thymocyte DNA damages
      induced by CP (150 mg/kg body weight) in mice. Thymocyte DNA damages was
      determined at 6, 12, 18, 24 h by single-cell gel electrophosphoresis assay (comet
      assay) after intraperitoneal injection of CP. The levels of DNA damage at 6, 12,
      18, 24 h were all significantly higher than that of the control group (p < 0.01).
      The highest level of DNA damage appeared at 18 h and then decreased at 24 h.
      Therefore, 18 h was selected to determine DNA damages induced by CP in subsequent
      experiments. In phase II experiment, 30 male KunMing mice were divided into three
      treatments: negative control (NC), positive control (PC) and nucleotides group
      (NG). Mice in NC and PC were fed nucleotide-free diet, and mice in NG were fed
      nucleotide-supplemented diet (supplemented with 0.25% nucleotides, a mixture
      containing equal amounts of AMP, CMP, GMP and UMP). Mice in PC and NG groups were
      injected with CP (150 mg/kg body weight) at 21 days. DNA damage in thymocytes was
      evaluated at 18 h after CP treatment. The results indicate that dietary
      nucleotides do not affect the weights of the thymus and the spleen, or their
      organ indices (p > 0.05), but significantly decrease the percentage of comet
      cells and comet tail sizes (p < 0.01). This study demonstrates that dietary
      nucleotides could reduce the level of thymocyte DNA damage induced by CP in mice.

PMID- 18336419
TI  - Abstracts of the American Academy of Veterinary Nutrition (AAVN), 6 June 2007,
      Seattle, Washington, USA.

PMID- 18336420
TI  - New author guidelines - clinical trials and conflict of interest.

PMID- 18336421
TI  - Analysis of gene transcript profiling and immunobiology in Shetland sheepdogs
      with dermatomyositis.
AB  - Dermatomyositis (DM) is a canine and human inflammatory disease of the skin and
      muscle that is thought to be autoimmune in nature. In dogs, DM occurs most often
      in the rough collie and Shetland sheepdog. Characteristic skin lesions typically
      develop on the face, ears, tail, and distal extremities. The severity of lesions
      varies and is thought to increase with stressful stimuli. Previous studies in the
      collie suggest that DM is inherited in an autosomal dominant fashion with
      incomplete penetrance. The work presented here concerns gene transcripts
      profiling and immunobiology of DM in the Shetland sheepdog. Gene transcript
      profiles were generated for affected and normal skin using a canine-specific
      oligonucleotide array having 49,929 probe sets. Two-hundred and eight-five gene
      transcripts, many of which are involved in immune function, were found to be
      differentially regulated in these tissues. Also reported are Western blot,
      immunohistochemistry, and immunofluorescence analyses which showed that staining
      patterns with sera from normal and affected dogs are quite similar. While our
      work suggests that canine DM is a disease that may be immune mediated, it did not
      detect the production of specific disease-associated autoantibodies.

PMID- 18336422
TI  - Gene (mRNA) expression in canine atopic dermatitis: microarray analysis.
AB  - Genes potentially involved in the pathology of canine atopic dermatitis (AD) were
      identified using gene expression microarrays. Total RNA extracted from skin
      biopsies was hybridized to an Agilent Technologies custom-designed 22K canine
      array. The arrays were analysed using Genedata Analyst software. Data were
      corrected for multiple hypothesis testing and tested for significance using the
      National Institute on Aging array analysis tool. For comparison, data were
      divided into separate groups: lesional atopic (n = 16), nonlesional atopic (n =
      17) and healthy controls (n = 9). Fifty-four genes were differentially expressed
      at a significance level of 0.05 in canine AD compared to healthy controls.
      Sixteen genes were differentially expressed in both nonlesional and lesional
      atopic skin, 26 genes only in nonlesional skin and 12 only in lesional skin.
      These genes were associated with innate immune and inflammatory responses, cell
      cycle, apoptosis, barrier formation and transcriptional regulation. The most
      dysregulated gene in lesional skin was S100A8, which showed an almost 23-fold
      increase in expression. This is a pro-inflammatory cytokine located in the
      epidermal differentiation complex. Microarray analysis is a novel technique in
      canine AD. Significant changes in gene expression were identified in atopic skin.
      These were relevant to skin barrier formation and the immune response, suggesting
      that they both participate in AD. Gene expression restricted to lesional skin may
      be involved in inflammatory changes, whereas those shared or restricted to
      nonlesional skin may reflect the atopic phenotype. Investigating gene
      polymorphisms in the targets identified in this study will help improve our
      understanding of the genetic basis of this disease.

PMID- 18336423
TI  - Assessment of cross-reactivity among five species of house dust and storage
      mites.
AB  - In vitro cross-reactivity among two house dust (Dermatophagoides farinae, D.
      pteronyssinus) and three storage (Acarus siro, Tyrophagus putrescentiae,
      Lepidoglyphus destructor) mites was examined in 20 mite-sensitive dogs with
      natural occurring atopic dermatitis (group A), 13 high-IgE beagles experimentally
      sensitized to D. farinae (group B), and five healthy beagles (group C).
      Intradermal testing (IDT) and serology for allergen-specific IgE demonstrated
      that co-sensitization for all possible pairs of the five mites was generally 45%
      or higher among group A dogs. In the same dogs, enzyme-linked immunosorbent assay
      cross-inhibition results indicated that each one of D. farinae, A. siro and T.
      putrescentiae was a strong inhibitor of all the remaining mites, whereas D.
      pteronyssinus was a strong inhibitor of L. destructor. A high number of positive
      IDT and serology test results for D. pteronyssinus, A. siro, T. putrescentiae and
      L. destructor were recorded among group B dogs. No conclusive evidence of
      exposure to these mites was found upon analysis of dust samples from their
      environment and their food for the presence of mites and guanine. Also, the
      number of positive test results was generally higher among group B than among
      group C dogs. Enzyme-linked immunosorbent assay cross-inhibition revealed that D.
      farinae was a strong inhibitor of D. pteronyssinus, A. siro and T. putrescentiae.
      Collectively, these results demonstrated extensive in vitro cross-reactivity
      among house dust and/or storage mites that can explain false-positive results
      upon testing of dust mite-sensitive dogs with atopic dermatitis.

PMID- 18336424
TI  - Spaying-induced coat changes: the role of gonadotropins, GnRH and GnRH treatment
      on the hair cycle of female dogs.
AB  - Although spaying can result in qualitative hair coat changes in dogs, the
      influence of spaying on the hair growth cycle has never been described. The study
      aims were to examine the effect of spaying and gonadotropin-releasing hormone
      (GnRH) treatment on canine hair coat, cycle stages of hair follicles, plasma
      gonadotropin concentrations and mRNA transcription of luteinizing hormone (LH)
      and GnRH receptors in hair follicles. Fifteen female dogs were examined before
      and 1 year after spaying and 24 spayed dogs before and after GnRH treatment.
      Spaying resulted in increased plasma gonadotropin concentrations and increased
      anagen : telogen ratio of hair follicles, but only 20% of the dogs developed coat
      changes. No differences were found in mRNA transcription of LH and GnRH
      receptors. GnRH treatment resulted in reduced plasma gonadotropin concentrations
      and improvement of coat changes in 79% of patients. This was associated with an
      increase in catagen hair follicles without changes in the anagen : telogen ratio.
      The present study demonstrated that spaying had an effect on the anagen : telogen
      ratio of hair follicles. Spaying-induced coat changes did not correlate with the
      anagen : telogen ratio. GnRH treatment reduced gonadotropin concentrations and
      reversed coat changes in some dogs, but had no effect on the hair growth cycle
      other than increasing the number of catagen hair follicles. A weak positive
      correlation between the plasma LH concentration and the anagen : telogen ratio
      was noted; however, our data did not suggest a direct receptor-mediated hormonal
      effect on the hair follicle. The present study did not identify the
      pathomechanism of spaying-induced coat changes.

PMID- 18336425
TI  - Symmetrical onychomadesis in Norwegian Gordon and English setters.
AB  - This study reports the condition onychomadesis affecting multiple claws in
      Norwegian Gordon and English setters. Medical records of and claw biopsies from
      18 Gordon and four English setters with onychomadesis of multiple claws were
      obtained from July 2005 to January 2007. Only dogs with symmetrical onychomadesis
      and no signs of concurrent disease were included. Histopathological features
      varied between dogs, but typically included interface dermatitis with
      subepidermal cleft formation, pigment incontinence, basal cell vacuolization and
      necrosis, spongiosis and lymphocytic exocytosis, a lymphocytic, plasmacytic
      subepidermal inflammation, and fibroplasia. In two dogs, histopathological signs
      of a superficial infection were present. The age of onset of disease varied
      between 2 and 7 years with a mean of 3.9 years, and was not correlated with
      vaccination time. Six of the affected dogs also had siblings with the disease.
      Due to the close relationship of the affected dogs, pedigree map analysis was not
      possible. Three dogs were euthanized because of the disease and two had regrowth
      of normal claws. Seventeen dogs had persistent onychodystrophy that typically was
      nonpainful during therapy which in most dogs consisted of fatty acid
      supplementation or prednisolone.

PMID- 18336426
TI  - Investigation of aural bacterial and fungal flora following otitis in captive
      okapi (Okapia johnstoni).
AB  - Ten cases of otitis in nine captive okapi were observed at a captive zoological
      institution. Duration of clinical signs ranged from 3 days to 7 months. Two
      individuals each had a recurrence. A variety of fungi and bacteria were isolated
      from the aural canals of healthy okapi and their environments. Numerous different
      bacterial and fungal pathogens were cultured. Surveys investigating the
      occurrence of ear disease and related environmental factors from 15 other
      institutions that house okapi revealed otitis was only seen at one institution.
      While it appears that many bacterial and fungal pathogens are found in the okapi
      ear canal, it is suspected that environmental conditions, such as fungal load,
      air and hay quality, humidity, and temperature may be predisposing factors
      leading to ear infections in this species.

PMID- 18336427
TI  - Prevalence and clinical signs of avipoxvirus infection in falcons from the Middle
      East.
AB  - The prevalence, cutaneous manifestations and concurrent clinical signs of
      avipoxvirus infection in 3706 falcons in two Middle Eastern countries are
      reported. Diagnosis was based on evidence of typical 'dry' skin lesions on
      featherless parts of the body and microscopic detection of Bollinger bodies in
      epithelial cells. Avipoxvirus was isolated from one representative case. Overall
      prevalence of cutaneous changes due to avipoxvirus infection did not differ
      significantly between Kuwait (2.7%) and Dubai (2.3%), although pox lesions were
      more prevalent on the feet of birds from Kuwait (67.4% vs. 50%) and more common
      on the eyelids of birds from Dubai (45.6% vs. 30.4%). Foot lesions were always
      present in birds with multiple infection sites. Some birds from Dubai had severe
      infection associated with weight loss, anorexia, lethargy, vomiting, central
      nervous system involvement and ultimately death.

PMID- 18336429
TI  - Pemphigus foliaceus-like drug reaction in a dog.

PMID- 18336430
TI  - Health care reform 2008.

PMID- 18336432
TI  - On risks of abortion.

PMID- 18336435
TI  - On the care of HIV-positive pregnant women.

PMID- 18336436
TI  - Evidence-based recommendations for depressive symptoms in postpartum women.
AB  - Postpartum depression is a serious health issue affecting 13% of women from
      diverse cultures. Despite the well-documented consequences of postpartum
      depression, it remains difficult to identify, and diverse practices relate to its
      prevention and treatment. Evidence-based interventions are essential to improve
      both maternal and infant health outcomes associated with pregnancy. This article
      describes the development process of an evidence-based practice guideline for
      postpartum depression and highlights the practice recommendations related to the
      confirmation, prevention, and treatment of depressive symptoms in postpartum
      mothers.

PMID- 18336437
TI  - Sexually transmitted infection/HIV risk reduction interventions in clinical
      practice settings.
AB  - African American women, particularly those who live in inner-city areas,
      experience disproportionately high rates of sexually transmitted infections
      including HIV. As there are currently no preventive vaccines for HIV and most
      sexually transmitted infections, prevention efforts must focus on behavioral risk
      reduction. Thus, culturally tailored interventions for African American women are
      needed to reduce their incidence of sexually transmitted infections including
      HIV. One place to intervene with inner-city African American women is in primary
      care settings. Primary care settings have the potential to reach a wide range of
      women, including those who may not proactively seek sexually transmitted
      infection/HIV prevention services. However, in order to be feasible for use in
      clinical settings, sexually transmitted infection/HIV risk reduction
      interventions must be brief and easily adapted for use with diverse clients in
      varied practice environments. To date, few brief sexually transmitted
      infection/HIV prevention interventions have been designed for use with African
      American women in primary care settings. Only one of these, the "Sister to
      Sister: Respect Yourself! Protect Yourself! Because You Are Worth It!"
      intervention, has demonstrated effectiveness in reducing sexual risk behaviors
      and sexually transmitted infection incidence. This article describes this 20
      minute, one-on-one nurse-led intervention for African American women and
      discusses considerations for its implementation in primary care and other
      clinical settings.

PMID- 18336438
TI  - Microarray technology applied to the complex disorder of preeclampsia.
AB  - Preeclampsia is a life-threatening perinatal complication with unknown etiology.
      Microarray technology has characterized global gene expression in complex
      disorders such as preeclampsia. Nursing research and future practice may
      incorporate findings from microarray analyses to identify susceptibility to and
      prevent disease, to diagnose early, and to design and monitor personalized
      therapies. This overview of microarray technology, with emphasis on how it can
      inform genomics of preeclampsia, may provide concepts to improve future maternal
      neonatal nursing care.

PMID- 18336439
TI  - Developmental origins theory from prematurity to adult disease.
AB  - Developmental Origins Theory has received little coverage in the nursing
      literature, even though it has received much attention in other sciences. The
      theory proposes that prenatal stress provokes adaptive changes in endocrine and
      metabolic processes that become permanently programmed and impact later adult
      health. This paper reviews the theory and describes the primary neuroendocrine
      mechanism of hypothalamic-pituitary-adrenal axis function. Supporting research
      evidence in preterm infant and adult samples is presented. Through knowledge of
      the theory and the long-term sequelae for preterm infants, nurses will have a
      different theoretical perspective and growing evidence to consider in their care
      for pregnant women and infants.

PMID- 18336440
TI  - Mind-body interventions during pregnancy.
AB  - OBJECTIVE: To examine published evidence on the effectiveness of mind-body
      interventions during pregnancy on perceived stress, mood, and perinatal outcomes.
      DATA SOURCES: Computerized searches of PubMed, Cinahl, PsycINFO, and the Cochrane
      Library. STUDY SELECTION: Twelve out of 64 published intervention studies between
      1980 and February 2007 of healthy, adult pregnant women met criteria for review.
      DATA EXTRACTION AND SYNTHESIS: Studies were categorized by type of mind-body
      modality used. Progressive muscle relaxation was the most common intervention.
      Other studies used a multimodal psychoeducation approach or a yoga and meditation
      intervention. The research contained methodological problems, primarily absence
      of a randomized control group or failure to adequately control confounding
      variables. Nonetheless, there was modest evidence for the efficacy of mind-body
      modalities during pregnancy. Treatment group outcomes included higher
      birthweight, shorter length of labor, fewer instrument-assisted births, and
      reduced perceived stress and anxiety. CONCLUSIONS: There is evidence that
      pregnant women have health benefits from mind-body therapies used in conjunction
      with conventional prenatal care. Further research is necessary to build on these
      studies in order to predict characteristics of subgroups that might benefit from
      mind-body practices and examine cost effectiveness of these interventions on
      perinatal outcomes.

PMID- 18336441
TI  - Effects of obesity on pregnancy.
AB  - OBJECTIVES: To examine physiologic and psychological outcomes associated with
      maternal obesity in pregnancy and patterns of pregnancy weight gain. To identify
      effective interventions for maternal obesity. DATA SOURCES AND STUDY SELECTION:
      Search of obesity and pregnancy research conducted over the past 10 years using
      CIHAHL, Medline ERIC, and PyscInfo databases. Studies including the following
      keywords were included in the review: obesity, weight gain, body image, pregnancy
      weight gain, pregnancy obesity complications, preeclampsia and gestational
      diabetes. Articles were included based on scientific merit and research outcomes.
      DATA SYNTHESIS AND CONCLUSIONS: Maternal obesity is a serious condition that
      significantly impacts not only mothers' health but also the health and future of
      their children. It is paramount that all levels of health care providers be aware
      of consequences of obesity and be knowledgeable of effective interventions. No
      effective long-term interventions have been demonstrated to prevent or control
      obesity during pregnancy. The paucity of published results of pregnancy and
      postpartum interventions to address weight gain in pregnancy suggests the need
      for more community and individualized based intervention studies, especially
      focusing on long-term effects.

PMID- 18336442
TI  - Understanding sexual abstinence in urban adolescent girls.
AB  - OBJECTIVES: To gain insight into the context of sexual abstinence and identify
      potential determinants of abstinence in this population. DESIGN: Four focus
      groups. PARTICIPANTS AND SETTING: Twenty-four, predominantly African American
      (88%) girls aged 14 to 19 years were recruited from urban health centers and
      youth development programs in Rochester, New York, between September and December
      2006. DATA ANALYSIS: Content analysis was used to analyze the four verbatim
      transcripts. Using analytic induction, groups were compared and contrasted at the
      micro (within-group) and macro (between-group) levels to identify themes.
      RESULTS: Four themes were identified that provided insight into how and why these
      girls remain abstinent despite being in sexually active social climates. They
      focused on the following: self-respect (I'm worth it), impact of mothers (Mama
      says ... think before you let it go), influence of boys and other peers (Boys
      will be boys), and potential negative consequences of sex (Hold on, there's a
      catch). CONCLUSIONS: Developing interventions to maintain abstinence, delay onset
      of sexual activity, and promote protected first and subsequent sexual contact in
      abstinent girls are key to decreasing future sexual risk. These findings suggest
      opportunities to develop HIV prevention strategies tailored to the needs of
      abstinent girls.

PMID- 18336443
TI  - Symptoms described by African American women evaluated for preterm labor.
AB  - OBJECTIVE: To describe symptoms, self-care for symptoms, and lay consultations of
      African American women later diagnosed with a likelihood of preterm labor (PTL).
      DESIGN: Qualitative descriptive study. SETTING: Two sites within the United
      States, one urban and one suburban high-risk maternity referral center.
      PARTICIPANTS: Twenty-five African American women presenting for emergent care and
      subsequently diagnosed as "rule out PTL." Five of the women later delivered
      before 37 weeks gestation, of whom 4 had a preterm low-birthweight infant
      (<or=2,500 g). MAIN OUTCOME MEASURE: Women's symptoms, self-care for symptoms,
      and lay consultations prior to seeking care for PTL. RESULTS: The most common
      reason for seeking care was due to "pains," and the second most common was
      "cramping," with most women (n = 17) seeking care within 4 to 24 hours of first
      experiencing symptoms. Importantly, 15 of the women first contacted
      friends/family members before seeking care. CONCLUSIONS: In African American
      women, implications about PTL teaching include adding the word "pain" as another
      teaching descriptor and targeting education to individuals whom the patient
      considers to be significant such as a close friend or family member.

PMID- 18336444
TI  - Midlife women's attitudes toward physical activity.
AB  - OBJECTIVE: To explore attitudes toward physical activity among a multiethnic
      group of midlife women. DESIGN: A qualitative cross-sectional study using an
      online forum. RECRUITMENT SETTINGS: Internet communities/groups for midlife women
      and for ethnic minorities. PARTICIPANTS: A multiethnic group of 15 midlife women.
      INSTRUMENTS: Ten online forum topics on attitudes toward physical activity and
      seven on ethnic-specific contexts. DATA ANALYSIS: Thematic analysis, involving
      line-by-line coding, categorization, and theme extraction. RESULTS: Six themes
      across all ethnic groups emerged from the data analysis process, although there
      were some ethnic differences in details related to each theme. The themes were
      (a) gendered experience, (b) physical activity as all body movements, (c) no time
      for physical activity, (d) environment matters, (e) health concerns made me do
      it, and (f) need a companion. CONCLUSIONS: Nurses need to consider and further
      investigate the influence of women's multiple roles, cultural factors, and
      environmental factors on physical activity in order to promote physical activity
      of midlife women.

PMID- 18336445
TI  - Current resources for evidence-based practice, March/April 2008.

PMID- 18336446
TI  - The impact of violence in the nursing workplace and women's lives.

PMID- 18336447
TI  - Recent and past intimate partner abuse and HIV risk among young women.
AB  - OBJECTIVE: To examine the associations between past intimate partner abuse
      experienced during adolescence (verbal and physical), recent intimate partner
      abuse (verbal, physical, and sexual), and HIV risk (as indicated by lack of
      condom use) for sexually active young adult women in relationships with male
      partners. DESIGN: Secondary data analysis of waves II and III of the National
      Longitudinal Study of Adolescent Health (Add Health). SETTING: The Add Health
      Study is a longitudinal, in-home survey of a nationally representative sample of
      adolescents. SAMPLE: Analyses involved 2,058 sexually active young adult women.
      MAIN OUTCOME MEASURES: HIV risk was measured by consistent condom use over the
      past 12 months. RESULTS: Physical and verbal abuse experienced in adolescence
      were associated with physical/verbal abuse experienced in young adulthood. Young,
      sexually active women experiencing no abuse in their relationships were more
      likely to consistently use condoms in the past 12 months than were their abused
      counterparts. CONCLUSION: A causal pathway may exist between prior abuse, current
      abuse, and HIV risk.

PMID- 18336448
TI  - Physical injury from intimate partner violence: measurement strategies and
      challenges.
AB  - Physical injury that occurs as a result of intimate partner violence needs to be
      treated to relieve pain, promote healing, and prevent infection. Detection of
      physical injury is an important component of the forensic examination because of
      its role in criminal justice proceedings. Better detection and measurement
      techniques are needed to quantify physical injuries and advance the science. This
      article addresses current practices of injury identification, challenges in
      injury measurement, and future directions for research.

PMID- 18336449
TI  - Incivility and bullying in the workplace and nurses' shame responses.
AB  - Incivility and bullying in the workplace are intimidating forces that result in
      shame responses and threaten the well-being of nurses. Some nurses are accustomed
      to tolerating behaviors that are outside the realm of considerate conduct and are
      unaware that they are doing so. These behaviors affect the organizational
      climate, and their negative effects multiply if left unchecked. Interventions for
      incivility and bullying behaviors are needed at both individual and
      administrative levels.

PMID- 18336450
TI  - Secondary traumatic stress in nurses who care for traumatized women.
AB  - Each year, thousands of women experience violence, and many of these are
      survivors of intimate partner violence. Each year, thousands of nurses provide
      physical and emotional care to these women. Nurses and employers need to
      recognize that exposures to traumatized women place nurses at risk for the
      development of secondary traumatic stress disorder. This article describes
      secondary traumatic stress, its risk factors, and its consequences. Workplace
      interventions and policies are recommended to reduce the avoidance, numbness,
      intrusive imagery, and other negative symptoms associated with secondary
      traumatic stress disorder.

PMID- 18336451
TI  - 12th Andrology Symposium/5th Symposium of the Hessian Center for Reproductive
      Medicine and EAA Center Giessen.

PMID- 18336452
TI  - Hidden pathogens uncovered: metagenomic analysis of urinary tract infections.
AB  - Urinary tract infections (UTIs) are the most common kidney and urologic diseases
      in industrial nations and are usually caused through faecal contamination of the
      urinary tract. In this study, we have examined 1449 urine specimens both by
      culture and by PCR. The majority of UTIs examined were caused by Escherichia coli
      (35.15%), followed by miscellaneous bacteria (23.03%), and by Enterococcus
      faecalis (19.39%). A large fraction of fastidious and anaerobic bacteria (22.43%)
      was not detected under culture conditions but only by using PCR. This group of
      bacteria evade the standard culture conditions used in routine diagnostic
      laboratories examining urine specimens. The molecular approach used broad-range
      16S rDNA PCR, denaturing high-performance liquid chromatography analysis,
      sequencing, and bioinformatic analysis to uncover these 'hidden' pathogens and is
      recommended in particular when examining leukocyte esterase-positive and culture
      negative urinary tract specimens.

PMID- 18336453
TI  - Sexually transmitted infections: impact on male fertility.
AB  - The impact of sexually transmitted diseases (STD) on male fertility is strongly
      dependent on the local prevalence of the STDs. In Western countries STD
      infections are of minor relevance. In other regions, i.e. Africa or South East
      Asia, the situation appears to be different. Acute urethritis could not be
      associated with male infertility. Chronic infections (gonorrhoea) can cause
      urethral strictures and epididymo-orchitis. Chlamydia trachomatis and Neisseria
      gonorrhoea can be transmitted to the female partner and cause pelvic inflammatory
      disease with tubal obstruction. Ureaplasma urealyticum may impair spermatozoa
      (motility, DNA condensation). Trichomonas vaginalis has, if any, only minor
      influence on male fertility. The relevance of viral infections (HPV, HSV) for
      male infertility is not resolved. Any STD increases the chances of transmission
      of the human immunodeficiency virus (HIV). The HIV infection is associated with
      infectious semen and the risk of virus transmission. Semen quality deteriorates
      with the progression of immunodeficiency. Special counselling of serodiscordant
      couples is needed. STDs should be treated early and adequately to prevent late
      sequelae for both men and women.

PMID- 18336454
TI  - Diagnosis and therapy of acute prostatitis, epididymitis and orchitis.
AB  - Acute genitourinary infections represent an important problem in daily urological
      practice. Standardised diagnostic procedures and therapeutic guidelines, as far
      as they exist, are mandatory to minimise the risk for severe sequelae and to
      optimise the therapeutic outcome. The present overview details diagnostic steps,
      therapeutic guidelines and the management of potential sequelae of acute
      prostatitis, acute epididymitis and acute orchitis. Acute prostatitis does not
      seem to represent a major diagnostic and therapeutic problem as long as prostatic
      abscess formation is absent. In acute epididymitis the development of epididymo
      orchitis is unpredictable despite adequate therapy and is of particular concern
      to andrologists because of its potential significance for male fertility. In
      contrast to these diseases, acute primary orchitis is a rare event, mostly
      occurring as mumps orchitis, without standardised treatment guidelines.

PMID- 18336455
TI  - Tuberculous epididymo-orchitis and prostatitis: a case report.
AB  - The worldwide prevalence of tuberculosis (TB) is still high, remaining almost
      unchanged over the past century. The genitourinary tract belongs to one of the
      most common sites of extrapulmonary TB. Although rare, epididymal TB may be the
      only clinically evident location of infection. We present an unusual case of
      tuberculous epididymitis and prostatitis, demonstrating the need for insistent
      diagnostic procedures to confirm diagnosis. The treatment of choice is primarily
      medical, consisting of a combination of three or four anti-TB drugs, sometimes
      combined with surgery.

PMID- 18336456
TI  - Chronic orchitis: a neglected cause of male infertility?
AB  - Infection and inflammation of the male reproductive tract are accepted as
      important aetiological factors of infertility. With regard to their impact on
      male reproductive function, orchitis and epididymo-orchitis due to local or
      systemic infection as well as noninfectious aetiological factors are of
      particular concern. There is clinical and pathological evidence that chronic
      inflammatory conditions of the testes can disrupt spermatogenesis and
      irreversibly alter both sperm number and quality. In the majority of patients,
      however, diagnosis is hampered by an asymptomatic course of the disease and
      unspecific clinical signs. Hence, respective epidemiological data are scarce. On
      the other hand, systematic histopathological work-up of testicular biopsies from
      infertile men indicates a high prevalence of inflammatory reactions. A
      characteristic pattern of inflammatory lesions with focal or multifocal,
      predominantly peritubular lymphocyte infiltration and concomitant damage of
      seminiferous tubules is seen in chronic orchitis of various origins. This
      supports the concept that induction of testicular inflammation is associated with
      a T-cell-mediated autoimmune response, i.e. disruption of the immune privilege.
      Moreover, despite the patchy distribution of the lesions, testicular volume and
      score counts for spermatogenesis may be significantly reduced. In conclusion,
      asymptomatic inflammatory reactions in the testis should not be neglected as an
      underlying cause or co-factor of male infertility. However, definitive diagnosis
      of chronic asymptomatic orchitis still requires testicular biopsy and guidelines
      for the therapeutic management are not yet available.

PMID- 18336457
TI  - Chronic epididymitis: impact on semen parameters and therapeutic options.
AB  - Chronic inflammatory conditions of the genital tract are frequently encountered
      in male fertility problems. The diagnosis, however, is hampered by a mostly
      asymptomatic course of the disease as well as inappropriate definitions and
      unspecific diagnostic criteria. With regard to their impact on male reproductive
      function, epididymitis seems to be more relevant than inflammation/infection of
      the prostate and/or seminal vesicles. Chronic epididymitis may result in reduced
      sperm count and motility. Impaired sperm motility because of epididymal
      dysfunction is frequently associated with an atypical staining behaviour of sperm
      tails. In many cases of chronic epididymitis, the number of leukocytes in the
      ejaculate is below the threshold of 10(6) per ml; therefore, consideration of
      additional markers of inflammation such as granulocyte elastase, pro-inflammatory
      cytokines (e.g. interleukin-6 or 8) or reactive oxygen species is helpful for
      establishing the diagnosis. Besides changes in the conventional sperm parameters,
      alterations in DNA integrity have been observed. Positive effects of
      antiphlogistic/antibiotic treatment on semen quality have been reported; however,
      controlled prospective studies are still lacking.

PMID- 18336458
TI  - Infections of the genitourinary tract and refertilisation operations.
AB  - Infections of the urinary tract are the aetiological reasons for primary
      infertility in up to 9% of infertile men. Taking into account that post-operative
      infection following vasovasostomy can lead to closure of the realigned deferent
      duct, special consideration should be given to consultation and treatment of
      vasovasostomy patients. In this paper, the influence of infection on operating
      procedures in infertility is described.

PMID- 18336459
TI  - Chronic bacterial prostatitis (NIH type II): diagnosis, therapy and influence on
      the fertility status.
AB  - In only approximately 10% of men with symptoms of chronic prostatitis/chronic
      pelvic pain syndrome bacterial infection of the prostate can be demonstrated by
      the Meares and Stamey 4-glass or the pre- and post-prostate massage (PPM) two
      glass test. Chronic bacterial prostatitis is mainly caused by Gram-negative
      uropathogens. The role of Gram-positives, atypicals and anaerobes is still
      debatable. For treatment, fluoroquinolones are considered the drugs of choice
      because of their favourable pharmacokinetic properties and their antimicrobial
      spectrum. As relapse and re-infection are a major problem in chronic bacterial
      prostatitis, only the results of studies with a follow up period of at least 6
      months are meaningful. Analysing the concentrations of various fluoroquinolones
      in prostatic and seminal fluid as well as in prostatic tissue, it becomes,
      however, obvious that fluoroquinolones differ not only in plasma concentrations,
      but also in their penetration ability to these sites. Nevertheless, the
      concentrations at the site of infection of most fluoroquinolones with this
      indication should be sufficient for the treatment of chronic bacterial
      prostatitis caused by susceptible pathogens. On the other hand, male accessory
      gland infection has been linked to male infertility. However, there is still a
      lack of evidence showing that bacterial prostatitis would have a negative impact
      on sperm quality.

PMID- 18336460
TI  - Acute bacterial prostatitis and chronic prostatitis/chronic pelvic pain syndrome:
      andrological implications.
AB  - There is a consensus on the diagnostic management of bacterial prostatitis (acute
      and chronic). In chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) the
      diagnostic approach remains unclear, because inflammatory and noninflammatory
      CP/CPPS might be one entity with varying findings over time. The WHO definition
      of male accessory gland infection does not differentiate between prostatitis,
      epididymitis, and other inflammatory alterations of the urethral compartment. The
      definition therefore cannot be further accepted as a rational tool for the
      diagnosis of prostatitis and related diseases in urological andrology. Therapy in
      infectious prostatitis is standardised and antibiotics are the primary agents.
      Andrological implications are well defined, side-effects are minimal. CP/CPPS
      therapy has the goal to reduce pelvic pain. However, treatment regimens are not
      as standardised. Andrological side-effects are well defined and mainly due to the
      functional background of these agents.

PMID- 18336461
TI  - Male accessory gland infection.
AB  - Male accessory gland infection (MAGI) is a consequence of canalicular spreading
      of agents via urethra, prostate gland, seminal vesicles, deferent duct,
      epididymis and testis. Haematogenous infections are rare. The main infectious
      agents are Neisseria gonorrhoeae and Chlamydia trachomatis, and also
      enterobacteriae at a lesser frequency. Characteristic symptoms of MAGI are
      leukocytospermia, enhanced concentration of cytokines and reactive oxygen
      species. As complications, obstruction of the ductus epididymidis and/or another
      duct section, impairment of spermatogenesis in orchitis, impairment of sperm
      function, and dysfunctions of the male accessory glands may occur. Reduction of
      male fertility is a rare consequence. The treatment has to consider specific
      antibiotics.

PMID- 18336462
TI  - Urogenital infections in reproductive medicine.
AB  - Urogenital infections with Chlamydia trachomatis belong to the most prevalent
      sexually-transmitted bacterial diseases. In women, they can cause chronic
      salpingitis with subsequent tubal infertility and ectopic pregnancies. In men, C.
      trachomatis can cause urethritis, prostatitis and epididymitis. Urogenital
      infections can be symptomatic or asymptomatic. Symptomatic urogenital infections
      might impair male fertility. In vitro, C. trachomatis affects sperm motility and
      viability. However, there is no clear evidence that asymptomatic urogenital
      infections have an adverse effect on male fertility. Because C. trachomatis can
      be sexually transmitted and lead to female infertility, it is also of
      significance in male infertility work-up. Because of their high sensitivity,
      nucleic acid amplification tests should be used to examine first-void urine
      specimens. Both partners should be treated. The role of Ureaplasma urealyticum in
      reproductive medicine has been discussed controversially. There is no evidence
      that U. urealyticum has a significant impact on female or male infertility.

PMID- 18336463
TI  - Haematospermia: diagnosis and treatment.
AB  - Men perceive a bloody ejaculate as an alarming physical symptom and often seek
      the help of urologists for explanation and treatment. After a complete urological
      step-by-step examination including imaging studies and flexible cystoscopy,
      malignancy or another significant disease can be ruled out in the majority of
      cases. However, many of these cases of haematospermia may still remain idiopathic
      and thus unsatisfactory for both the patient and his physician. The following
      paper reviews the aetiology, the diagnostic work-up escalation and the treatment
      options of haematospermia.

PMID- 18336464
TI  - Urogenital infections and male sexuality: effects on ejaculation and erection.
AB  - The relation of urogenital infections and sexual dysfunction in men was largely
      neglected in the past but has attracted increasing interest recently. Despite
      direct anatomical and physiological interactions of the pelvic structures, an
      adverse effect of chronic prostatitis on quality of life and well-being should be
      considered to be another crucial point for any sexual disorder. Erectile
      dysfunction, premature ejaculation and painful ejaculation are the leading sexual
      symptoms in urogenital infections. On the other hand, chronic prostatitis has
      been found with a high frequency especially in men presenting with secondary
      premature ejaculation and the importance of a careful physical and
      microbiological examination of the prostate before any pharmacologic or
      psychosexual therapy for sexual disorder should be considered.

PMID- 18336465
TI  - The issue of prostate cancer evaluation in men with elevated prostate-specific
      antigen and chronic prostatitis.
AB  - Elevated levels of prostate-specific antigen (PSA) in men may result from a
      variety of causes, such as prostate cancer, benign prostatic hyperplasia, acute
      urinary tract infection, and bacterial prostatitis. In recent years, several
      studies have also demonstrated a relationship between chronic prostatitis/chronic
      pelvic pain syndrome and increased PSA levels. However, asymptomatic patients are
      not routinely screened for this diagnosis before transrectal biopsy is performed
      to rule out prostate cancer. These asymptomatic men with elevated PSA levels
      frequently have evidence of inflammation when their expressed prostatic
      secretions are examined, or on their prostate biopsy specimens. This raises the
      problem of appropriate evaluation in the presence of chronic prostatitis and
      elevated PSA levels--not only in prostate cancer screening programmes, but also
      in cancer-negative biopsy findings. Evidence from the literature indicates that
      antimicrobial treatment may lower the PSA levels to what is considered the normal
      range. Despite that, general recommendations for the practical management are
      lacking and undetected prostate cancer in men with chronic prostatitis remains a
      difficult issue.

PMID- 18336466
TI  - Proliferative inflammatory atrophy: a background lesion of prostate cancer?
AB  - Proliferative inflammatory atrophy (PIA) belongs to the atrophic lesions that
      frequently occur in the prostate. The location of PIA in the periphery of the
      gland near to prostate carcinoma or even showing direct transition to malignant
      or pre-malignant epithelia suggested a connection between PIA and prostate
      cancer. Further findings in PIA, such as imbalance between proliferation and
      apoptosis and detection of molecular-biological abnormalities specific for
      oxidative stress or malignancy, supported this hypothesis. Recently,
      epidemiological studies including large cohorts of patients have been undertaken
      in order to investigate the causal connection between PIA and prostate carcinoma.
      The current understanding of PIA allows us to consider it as a benign lesion with
      certain genetic instability which can degenerate into prostate intraepithelial
      neoplasia or carcinoma, provided that the balance between anti-carcinogens and
      carcinogens is perturbed. To evaluate the role of PIA as a precursor lesion of
      prostate cancer, further examinations of genetic or epigenetic aberrations are
      required.

PMID- 18336467
TI  - p21(Cip1) expression is increased in ambient oxygen, compared to estimated
      physiological (5%) levels in rat muscle precursor cell culture.
AB  - OBJECTIVE: While it is common practice to culture cells in the presence of
      ambient oxygen (approximately 21% O2), O2 level observed in the physiological
      environment is often much lower. Previous efforts to culture a variety of
      different stem cells, including muscle precursor cells (MPC), under O2 conditions
      that better mimic in vivo conditions have resulted in enhanced proliferation. In
      the present study, we hypothesized that 20% O2 in culture represents a sufficient
      stimulus to cause increased expression of two key negative regulators of the cell
      cycle Cip/Kip family of cyclin-dependent kinase inhibitors, p21(Cip1) and
      p27(Kip1), in MPCs. MATERIALS AND METHODS: MPCs were isolated from Fischer 344 x
      Brown Norway F(1) hybrid male rats and O2 was adjusted in culture using a tri-gas
      incubator. RESULTS: 5-Bromo-2'-deoxyuridine incorporation, cell number and
      nuclear proliferating cell nuclear antigen expression were all decreased after 48
      h culture in 20% O2, compared to 5% O2. Twenty per cent O2 had no effect on
      either p27(Kip1) promoter activity or protein expression. Although p21(Cip1)
      promoter activity remained unchanged between 5% and 20% O2, there were
      significant increases in both p21(Cip1) mRNA and protein expression. Furthermore,
      20% O2 caused an increase in p21(Cip1) mRNA stability and p53 transcription
      factor activity. CONCLUSION: These findings are considered important because they
      reveal p21(Cip1) as a critical regulatory protein that needs to be considered
      when interpreting proliferation data from MPCs studied in culture. In addition,
      O2-dependent regulation of MPC proliferation is relevant to conditions, including
      sarcopenia, heart failure, cancer and muscular dystrophy, where increased
      oxidative stress exists.

PMID- 18336468
TI  - Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth
      muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent
      kinases.
AB  - OBJECTIVE: Platelet-activating factor (PAF) is implicated in pathogenesis of
      persistent pulmonary hypertension of the neonate (PPHN); PAF is a mitogen for
      lung fibroblasts. PAF's role in pulmonary vascular smooth muscle cell (PVSMC)
      proliferation and in hypoxia-induced pulmonary vein (PV) remodelling has not been
      established and mechanisms for PAF's cell-proliferative effects are not well
      understood. We investigated involvement of PAF and PAF receptors in PVSMC
      proliferation. MATERIALS AND METHODS: Cells from pulmonary arteries (SMC-PA) and
      veins (SMC-PV) were serum starved for 72 h in 5% CO2 in air (normoxia). They were
      cultured for 24 h more in normoxia or 2% O(2) (hypoxia) in 0.1% or 10% foetal
      bovine serum with 5 microCi/well of [(3)H]-thymidine, with and without 10 nm PAF.
      Nuclear factor-kappa B (NF-kappaB), CDK2 and CDK4 protein expression, and their
      roles in cell proliferation control were studied. RESULTS: PAF and hypoxia
      increased SMC-PA and SMC-PV proliferation. WEB2170 inhibited PAF-induced cell
      proliferation while lyso-PAF had no effect. SMC-PV proliferated more than SMC-PA
      and PAF plus hypoxia augmented NF-kappaB protein expression. NF-kappaB inhibitory
      peptide attenuated PAF-induced cell proliferation by 50% and PAF increased CDK2
      and CDK4 protein expression. The data show that hypoxia and PAF up-regulate PVSMC
      proliferation via PAF receptor-specific pathway involving NF-kappaB, CDK2 and
      CDK4 activations. CONCLUSION: They suggest that in vivo, in foetal lung low
      oxygen environment, where PAF level is high, proliferation of PVSMC will occur
      readily to modulate PV development and that failure of down-regulation of PAF
      effects postnatally may result in PPHN.

PMID- 18336469
TI  - Short-period hypoxia increases mouse embryonic stem cell proliferation through
      cooperation of arachidonic acid and PI3K/Akt signalling pathways.
AB  - Hypoxia plays important roles in some early stages of mammalian embryonic
      development and in various physiological functions. This study examined the
      effect of arachidonic acid on short-period hypoxia-induced regulation of G(1)
      phase cell-cycle progression and inter-relationships among possible signalling
      molecules in mouse embryonic stem cells. Hypoxia increased the level of hypoxia
      inducible factor-1alpha (HIF-1alpha) expression and H2O2 generation in a time
      dependent manner. In addition, hypoxia increased the levels of cell-cycle
      regulatory proteins (cyclin D(1), cyclin E, cyclin-dependent kinase 2 (CDK2) and
      CDK4). Maximum increases in the level of these proteins and retinoblastoma
      phosphorylation were observed after 12-24 h of exposure to hypoxic conditions,
      and then decreased. Alternatively, the level of the CDK inhibitors, p21(Cip1) and
      p27(Kip1) were decreased. These results were consistent with the results of [3H]
      thymidine incorporation and cell counting. Hypoxia also increased the level of
      [3H]-arachidonic acid release and inhibition of cPLA(2) reduced hypoxia-induced
      increase in levels of the cell-cycle regulatory proteins and [3H]-thymidine
      incorporation. The level of cyclooxygenase-2 (COX-2) was also increased by
      hypoxia and inhibition of COX-2 decreased the levels of cell-cycle regulatory
      proteins and [3H]-thymidine incorporation. Indeed, the percentage of cells in S
      phase, levels of cell cycle regulatory proteins, and [3H]-thymidine incorporation
      were further increased in hypoxic conditions with arachidonic acid treatment
      compared to normoxic conditions. Hypoxia-induced Akt and mitogen-activated
      protein kinase (MAPK) phosphorylation was inhibited by vitamin C (antioxidant,
      10(-3) M). In addition, hypoxia-induced increase of cell-cycle regulatory protein
      expression and [(3)H]-thymidine incorporation were attenuated by LY294002 (PI3K
      inhibitor, 10(-6) M), Akt inhibitor (10(-6) M), rapamycin (mTOR inhibitor, 10(-9)
      M), PD98059 (p44/42 inhibitor, 10(-5) M), and SB203580 (p38 MAPK inhibitor, 10(
      6) M). Furthermore, hypoxia-induced increase of [(3)H]-arachidonic acid release
      was blocked by PD98059 or SB203580, but not by LY294002 or Akt inhibitor. In
      conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G(1)
      phase cyclins D(1) and E, and CDK 2 and 4, in mouse embryonic stem cells through
      the cooperation of PI3K/Akt/mTOR, MAPK and cPLA(2)-mediated signal pathways.

PMID- 18336470
TI  - Transforming growth factor-beta1 regulates the fate of cultured spinal cord
      derived neural progenitor cells.
AB  - OBJECTIVES: We have evaluated the physiological roles of transforming growth
      factor-beta1 (TGF-beta1) on differentiation, migration, proliferation and anti
      apoptosis characteristics of cultured spinal cord-derived neural progenitor
      cells. METHODS: We have used neural progenitor cells that had been isolated and
      cultured from mouse spinal cord tissue, and we also assessed the relevant
      reaction mechanisms using an activin-like kinase (ALK)-specific inhibitory system
      including an inhibitory RNA, and found that it involved potential signalling
      molecules such as phosphatidylinositol-3-OH kinase (PI3K)/Akt and mitogen
      activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2).
      RESULTS AND CONCLUSIONS: Transforming growth factor-beta1-mediated cell
      population growth was activated after treatment and was also effectively blocked
      by an ALK41517-synthetic inhibitor (4-(5-benzo(1,3) dioxol-5-yl-4-pyridine-2-yl
      1H-imidazole-2-yl) benzamide (SB431542) and ALK siRNA, thereby indicating the
      involvement of SMAD2 in the TGF-beta1-mediated growth and migration of these
      neural progenitors cells (NPC). In the present study, TGF-beta1 actively induced
      NPC migration in vitro. Furthermore, TGF-beta1 demonstrated extreme anti
      apoptotic behaviour against hydrogen peroxide-mediated apoptotic cell death. At
      low dosages, TGF-beta1 enhanced (by approximately 76%) cell survival against
      hydrogen peroxide treatment via inactivation of caspase-3 and -9. TGF-beta1
      treated NPCs down-regulated Bax expression and cytochrome c release; in addition,
      the cells showed up-regulated Bcl-2 and thioredoxin reductase 1. They also had
      increased p38, Akt and ERK1/2 phosphorylation, showing the involvement of both
      the PI3K/Akt and MAPK/ERK1/2 pathways in the neuroprotective effects of TGF
      beta1. Interestingly, these effects operate on specific subtypes of cells,
      including neurones, neural progenitor cells and astrocytes in cultured spinal
      cord tissue-derived cells. Lesion sites of spinal cord-overexpressing TGF-beta1
      mediated prevention of cell death, cell growth and migration enhancement activity
      have been introduced as a possible new basis for therapeutic strategy in
      treatment of neurodegenerative disorders, including spinal cord injuries.

PMID- 18336471
TI  - Are progenitor cells pre-programmed for sequential cell cycles not requiring
      cyclins D and E and activation of Cdk2?
AB  - OBJECTIVES: Based on studies of unicellular organisms or cultured mammalian
      cells, the generally accepted model of cell-cycle regulation has been developed
      in which sequential (scheduled) expression of cyclins D, E, A and B and
      activation of Cdk2 and Cdk1 takes place. It is assumed that the same model is
      applicable both in vivo and in vitro. MATERIALS AND METHODS: In the present
      study, we compared proliferating marrow cells freshly isolated from healthy
      individuals with proliferating lymphocytes in cultures. RESULTS: We demonstrate
      that during progression of freshly collected human bone marrow cells through
      G(1), S and G(2)/M, only Cdk1 combined with cyclins A and B(1) was distinctly
      present and active, and its activity gradually increased. In contrast, in vitro
      growing mitogen-stimulated lymphocytes had perfectly scheduled sequential
      expression of all four cyclins and Cdk1 and Cdk2 activities. CONCLUSION: Our
      findings demonstrate that the pattern of cyclin expression and Cdk activity in
      bone marrow in vivo is distinctly different from the one observed for normal
      cells in vitro. Because proliferating bone marrow cells are predominantly
      expanding populations of committed progenitors, it is likely that during the
      expansion phase their cell-cycle progression is pre-programmed, being driven
      solely by Cdk1 combined either with cyclin A or with cyclin B(1). Expansion of
      progenitor cells thus may not require the early steps of cell-cycle regulation,
      associated with triggering progression by availability of growth factors and
      mitogens.

PMID- 18336472
TI  - Conjugated linoleic acids differentially alter polyp number and diameter in the
      Apc(min/+) mouse model of intestinal cancer.
AB  - OBJECTIVE: Dietary conjugated linoleic acids (CLA) have had many health benefits
      claimed for them, including antineoplastic actions. MATERIALS AND METHODS: The
      effects of the predominant forms of CLA, namely the c9t11 and t10c12 isomers, or
      a mixture of these on polyp development, were investigated in the Apc(Min/+)
      mouse. CLAs have also been linked to altered rates of cell renewal and cell
      proliferation so this was also studied, as was a further means of increasing
      tissue mass, namely crypt fission. RESULTS: The stomach and small intestine were
      significantly heavier in the t10c12, and in the mixture-treated groups (P <
      0.001). Crypt fission was increased in the middle small intestine by the t10c12
      diet while colonic weight was reduced by c9t11 provision and crypts were 20%
      shorter. The t10c12 and the mixture significantly reduced polyp number in the
      proximal small intestine but they increased polyp diameter in the middle and
      distal small intestine, to an extent that the polyp burden was significantly
      increased at these sites. All CLAs significantly reduced polyp number in the
      colon, but the mixture significantly increased polyp diameter in the colon.
      CONCLUSION: Increased polyp diameter associated with t10c12 diet and especially
      with the mixture is a cause of concern, as this is the commercially available
      form. The naturally occurring isomer, c9t11 decreased colonic polyp number and
      did not increase diameter, suggesting that this natural isomer is the most likely
      to be protective.

PMID- 18336473
TI  - Human plasma accelerates immortalization of B lymphocytes by Epstein-Barr virus.
AB  - OBJECTIVE: Serum and plasma contain species-specific factors that modulate cell
      population growth and function, and that are required for proliferation of most
      cell cultures. Foetal calf serum (FCS) is the most common source of these growth
      factors. We studied the effect of human plasma (HP) on the immortalization
      process of B lymphocytes by Epstein-Barr virus (EBV) was studied. MATERIALS AND
      METHODS: The effect of HP as compared to FCS was done through assessment of cell
      proliferation. RESULTS: It was found that HP (autologous and non-autologous
      plasma) is more effective than FCS in generating lymphoblastoid cell lines,
      regardless of EBV status of the donors: 65% of HP-supplemented cultures developed
      into lymphoblastoid cell lines by 7-14 culture days, as compared to 16% of
      cultures with FCS. In addition, 6% of HP-supplemented cultures did not achieve
      becoming lymphoblastoid cell lines by day 35 in comparison to 94% of cultures
      with FCS. The higher proliferative effect of HP was not altered by heat
      inactivation or filtration. HP maintained its proliferative activity at 4 degrees
      C over 8 months, thus indicating that HP contains a stable growth factor(s),
      which accelerates B-lymphocyte immortalization. CONCLUSION: The results support
      other studies that recommend the use of autologous plasma for tissue culture,
      mainly in the case of autologous transplantation. Furthermore, the use of HP
      allows preparation of lymphoblastoid cell lines from a small amount of peripheral
      blood in a shorter period of time and with a higher rate of success.

PMID- 18336474
TI  - Influence of supramammary lymph node extract on in vitro cell proliferation.
AB  - OBJECTIVES: Experiments were conducted to evaluate whether or not bovine
      supramammary lymph node extract (LNE) could support cell proliferation when it
      was substituted for bovine growth serum (BGS) in cell culture media. MATERIALS
      AND METHODS: Two different preparations of LNE were tested. The first yielded
      protein concentration of 3 mg/mL and the second contained 27 mg/mL protein. Three
      cell lines (MDA-MB-435, MAC-T and 1C6) were used in serum starvation assays to
      evaluate LNE. Cell proliferation assays were used to determine growth stimulation
      in the presence of LNE, and short-term or rapid adaptation cultures were
      evaluated for LNE effects on cell survival. RESULTS: Heat-inactivated preparation
      1 supported cell proliferation as well as or better (12-39%) than BGS following 2
      days of serum starvation in culture. The second lymph node preparation provided a
      stimulatory effect (263-702% greater than BGS across all cell lines) following
      serum starvation at 2.7 and 5.4 mg/mL protein supplementation. A gradual
      adaptation process with lymph node supplementation into media maintained cell
      population growth on a short-term basis. However, once cells were trypsinized or
      scraped and re-seeded into 2.7 mg/mL LNE protein containing media, cells were
      unable to re-adhere, leaving them detached, and eventually appearing to be dead.
      CONCLUSIONS: Substitution of BGS with LNE protein dramatically stimulated cells
      to proliferate, but did not allow for rapid cell population growth adaptation in
      vitro.

PMID- 18336475
TI  - Establishment of a gastric epithelial progenitor cell line from a transgenic
      mouse expressing the simian virus 40 large T antigen gene in the parietal cell
      lineage.
AB  - OBJECTIVE: In this study the gastric mucosa of transgenic mice expressing the
      simian virus 40 large T antigen gene in the parietal cell lineage is used to
      establish and characterize a new epithelial progenitor cell line. In these mice,
      proliferation and amplification of preparietal cells preclude their maturation
      into acid-secreting parietal cells leading to achlorohydria, hyperplasia,
      dysplasia and eventually gastric adenocarcinoma. MATERIALS AND METHODS:
      Enzymatically dispersed gastric epithelial cells were cultured, cloned and
      screened using immunohistochemical methods, for expression of a variety of
      biomarkers of differentiated pit, parietal, enteroendocrine and neck/zymogenic
      cells. RESULTS: A biomarker-deficient cell line whose ultrastructural features
      resembled those of mouse gastric epithelial progenitor cells was established.
      Treatment with either hydrocortisone or oestrogen significantly enhanced
      proliferation of these cells, whereas retinoic acid inhibited their growth. No
      change in differentiation was detected with any of these treatments; however,
      when these cells were injected subcutaneously into nude mice, they proliferated
      to form tumours and undergo partial differentiation towards parietal cell
      lineage. CONCLUSION: This mouse gastric epithelial progenitor cell line could be
      useful as an in vitro model to study growth properties, proliferation and
      differentiation of a subpopulation of gastric epithelial progenitor cells and
      also to study gastric carcinogenesis.

PMID- 18336476
TI  - Assessment of the potential of progenitor stem cells extracted from human
      peripheral blood for seeding a novel vascular graft material.
AB  - OBJECTIVE: A novel nanocomposite has recently been developed based on polyhedral
      oligomeric silsesquioxane attached by direct reaction onto a urethane segment, as
      a potential vascular graft material; its trade name is UCL-Nano. The UCL-Nano has
      been demonstrated to have similar viscoelastic properties to the walls of a
      natural artery, to be resistant to degradation and to be able to sustain
      endothelial cell seeding. Human peripheral blood contains both circulating
      endothelial cells and endothelial progenitor cells, which may be suitable for
      conduit seeding. The aim of this study was to develop a system with the potential
      to deliver an endothelial cell-seeded bypass graft in a realistic time frame.
      MATERIALS AND METHODS: Endothelial progenitor cells and circulating endothelial
      cells were isolated from human peripheral blood and were characterized by
      fluorescent-activated cell sorting, reverse transcriptase-polymerase chain
      reaction and immunohistochemistry. Isolated cells were seeded on nanocomposite
      and were maintained in culture for 35 days. RESULTS: The UCL-Nano was
      successfully seeded with cells and a confluent cell layer was achieved after 14
      day culture. Cells remained viable and confluent on the nanocomposite for 35
      days. CONCLUSION: In conclusion, these results suggest that this process has
      potential both for a realistic and achievable two-stage seeding process for
      vascular bypass grafts and for the potential development of a device, with the
      aim of achieving in situ seeding once implanted.

PMID- 18336477
TI  - Stromal cell-derived factor-1 promotes bone marrow-derived cells differentiation
      to cardiomyocyte phenotypes in vitro.
AB  - OBJECTIVE: Recent studies have demonstrated the potential of bone marrow-derived
      cells (BMDC) to differentiate into cardiomyocytes. Up-regulation of stromal cell
      derived factor-1 (SDF-1), a member of the chemokine CXC subfamily, mediating
      recruitment of BMDC has been documented in infarcted myocardium; however, it
      remains unknown whether SDF-1 plays a role in cardiomyogenesis of BMDC. MATERIALS
      AND METHODS: Adherent BMDCs were cultured with SDF-1, or specific inhibitor for
      PI3K, CXCR4 or Akt with SDF-1, respectively. After 2 weeks, mRNAs and proteins
      from BMDCs were examined. RESULTS: Two weeks after supplementation with SDF-1,
      either murine or human adherent BMDC cultured in vitro expressed cardiac specific
      mRNAs (NKX2.5, atrial natriuretic factor and heavy chain beta-myosin) and
      proteins (troponin I and heavy chain cardiac myosin), and expression levels were
      partly decreased by combined treatment of CXCR4, PI3K or Akt inhibitor, with SDF
      1. CONCLUSIONS: The novel findings suggest that beyond its role in mobilization
      and homing of BMDC, SDF-1 can promote BMDC to give rise to cardiomyocyte
      phenotypes in vitro, and the SDF-1/CXCR4/PI3K/Akt pathway may be one of the
      molecular mechanisms regulating cardiomyogenesis.

PMID- 18336478
TI  - Collagens, stromal cell-derived factor-1alpha and basic fibroblast growth factor
      increase cancer cell invasiveness in a hyaluronan hydrogel.
AB  - OBJECTIVE: Beyond to control of cell migration, differentiation and
      proliferation, the extracellular matrix (ECM) also contributes to invasiveness of
      human cancers. As the roles of hyaluronan (HA) and collagens in this process are
      still controversial, we have investigated their involvement in cancer
      pathogenesis. MATERIALS AND METHODS: With this aim in view, we developed a three
      dimensional matrix, as reticulate HA hydrogel alone or coated with different
      collagens, in which cells could invade and grow. RESULTS: We show that cancer
      cells, which were non-invasive in a single HA hydrogel, acquired this capacity in
      the concomitant presence of type I or III collagens. Both types of ECM compound,
      HA and collagens, possess the capacity to stimulate production of metalloprotease
      2, recognized otherwise as a factor for poor cancer prognosis. HA-provoked
      cellular invasiveness resulted from CD44-mediated increase in cytosolic [Ca2+]
      and its subsequent hydrolysis due to ADAM (a disintegrin and metalloprotease)
      proteolytic activity. Interestingly, this mechanism seemed to be absent in non
      invasive cancer cell lines. CONCLUSION: Furthermore, using basic fibroblast
      growth factor and stromal cell-derived factor-1alpha, we also show that this
      three-dimensional reticulate matrix may be considered as a valuable model to
      study chemokinetic and chemotactic potentials of factors present in tumour
      stroma.

PMID- 18336479
TI  - Imaging of cell trafficking and metastases of paediatric rhabdomyosarcoma.
AB  - OBJECTIVE: The aim of this study was to establish a preclinical mouse model to
      study metastases of paediatric rhabdomyosarcoma at the macroscopic and cellular
      levels, with different imaging methods. EXPERIMENTAL DESIGN: The alveolar
      rhabdomyosarcoma cell line Rh30 was stably transfected with the red fluorescent
      protein (DsRed2) then was xenotransplanted (intravenous injection [n = 8], and
      footpad injection [n = 8]) into nude mice (NMRI nu/nu). Macroscopic imaging of
      metastases was performed using DsRed2-fluorescence and flat-panel volumetric
      computed tomography scan. In a further series of animals (n = 8), in vivo cell
      trafficking of rhabdomyosarcoma cells using cellular imaging with an Olympus
      OV100 variable-magnification small-animal imaging system was used. RESULTS:
      Metastases in the pelvis, thoracic wall and skin were visualized by fluorescence
      imaging. Pelvic metastases were found after tail vein injection and at other
      metastatic sites after footpad injection. Flat-panel volumetric computed
      tomography scan data allowed highly specific analysis of contrast between tumour
      and surrounding tissue. Correlation between fluorescence and flat-panel
      volumetric computed tomography scan imaging data was observed. Single-cell
      imaging visualized tumour cells in the vessels and demonstrated the arrest of
      tumour cells at vessel junctions followed by extravasation of the tumour cells.
      CONCLUSION: We established a model for visualization of experimental metastatic
      invasion and describe relevant tools for imaging childhood rhabdomyosarcoma
      metastases at the macroscopic and cellular levels. Imaging of cell trafficking
      visualized the behaviour of tumour cells and development of metastases by
      accumulation and extravasation of rhabdomyosarcoma cells.

PMID- 18336481
TI  - Safety in anaesthesia: reporting incidents and learning from them.

PMID- 18336482
TI  - Safety in anaesthesia: a study of 12,606 reported incidents from the UK National
      Reporting and Learning System.
AB  - The incident reporting database at the National Patient Safety Agency was
      interrogated on the nature, frequency and severity of incidents related to
      anaesthesia. Of 12,606 reports over a 2-year period, 2842 (22.5%) resulted in
      little harm or a moderate degree of harm, and 269 (2.1%) resulted in severe harm
      or death, with procedure or treatment problems generating the highest risk. One
      thousand and thirty-five incidents (8%) related to pre-operative assessment, with
      harm occurring in 275 (26.6%), and 552 (4.4%) related to epidural anaesthesia,
      with harm reported in 198 (35.9%). Fifty-eight occurrences of anaesthetic
      awareness were also examined. This preliminary analysis is not authoritative
      enough to warrant widespread changes of practice, but justifies future
      collaborative approaches to reduce the potential for harm and improve the
      submission, collection and analysis of incident reports. Practitioners,
      departments and professional bodies should consider how the information can be
      used to promote patient safety and their own defensibility.

PMID- 18336483
TI  - The effect of bolus administration of remifentanil on QTc interval during
      induction of sevoflurane anaesthesia.
AB  - Stimulation of the sympathetic nervous system associated with tracheal intubation
      causes corrected QT (QTc) interval prolongation. We postulated that the use of
      remifentanil during induction of anaesthesia might prevent this. Sixty
      unpremedicated, ASA grade 1 patients were selected and randomly allocated to
      receive either saline (group S), remifentanil 0.5 microg x kg(-1) (group R 0.5)
      or remifentanil 1.0 microg x kg(-1) (group R1.0) 1 min before laryngoscopy. The
      QTc interval was significantly prolonged immediately following intubation in
      group S and group R0.5, but it remained stable in group R1.0, compared with the
      QTc interval just before laryngoscopy. It is concluded that the administration of
      remifentanil 1.0 microg x kg(-1) before intubation can prevent the prolongation
      of the QTc interval associated with tracheal intubation during induction of
      anaesthesia with sevoflurane.

PMID- 18336484
TI  - Effects of methylene blue on propofol requirement during anaesthesia induction
      and surgery.
AB  - Delayed emergence from anaesthesia and neurological disturbances have been
      reported in patients undergoing parathyroidectomy who received methylene blue
      (MB) pre-operatively. We hypothesised that MB would decrease propofol
      requirements. The Bispectral index (BIS) and a target-controlled infusion of
      propofol were used in two groups of 11 matched patients. Patients in one group
      were pretreated with MB. During induction, clinical sedation scores and BIS
      values were significantly lower at the predicted effect-site propofol
      concentration of 2 microg x ml(-1) in the MB compared with the control group.
      Intra-operatively, although similar BIS values were achieved in the two groups,
      patients pretreated with MB required a mean 50% lower dose of propofol compared
      with controls. In view of these findings, care should be taken to ensure an
      adequate depth of anaesthesia by titrating the administration of anaesthetic
      agents whenever MB is infused peri-operatively.

PMID- 18336485
TI  - The rate of alveolar-capillary uptake of sevoflurane and nitrous oxide following
      anaesthetic induction.
AB  - The rate of anaesthetic gas uptake from the breathing system has been extensively
      measured, but this does not reflect the true rate of early gas uptake by
      pulmonary blood, which drives inhalational induction of anaesthesia. In eight
      patients undergoing coronary bypass surgery, we measured the rate of alveolar
      capillary uptake of anaesthetic gases up to 30 min following introduction of 0.5%
      sevoflurane and 33% nitrous oxide using the reverse Fick method, in which blood
      partial pressures were measured using a headspace equilibration technique.
      Simultaneous measurements of gas uptake from the breathing system were made by
      indirect calorimetry. Measured rates of sevoflurane and nitrous oxide uptake from
      the breathing system agreed well with previously described formulae when adjusted
      for inspired concentration. The time course of alveolar-capillary gas uptake
      followed a characteristic rising curve peaking at 3-4 min and then exponentially
      declining, and for nitrous oxide was significantly higher than previously
      estimated.

PMID- 18336486
TI  - Unanticipated difficult airway management in anaesthetised patients: a
      prospective study of the effect of mannequin training on management strategies
      and skill retention.
AB  - This prospective study on a medium-fidelity simulator (SimMan, Laerdal Medical
      Corporation, Wappingers Falls, NY, USA) examined the management of unanticipated
      difficult airway by 21 anaesthetists and the effect of training in this context.
      There were two scenarios investigated: 'cannot intubate, can ventilate' (CI) and
      'cannot intubate, cannot ventilate' (CICV). Following initial evaluation,
      volunteers underwent training in the 'Difficult Airway Society' (DAS) algorithms
      and associated technical skills. At 6-8 weeks and 6-8 months, performance was
      compared with the initial evaluation. There was a more structured approach
      following training (p < 0.05), which was sustained at 6-8 months, but only for
      the CICV scenario (p < 0.01). In CI, use of standard and intubating laryngeal
      mask airway increased following training (p = 0.021). This was sustained over
      time (p = 0.01). In both scenarios there was a reduced incidence of equipment
      misuse (p < 0.0005), which was sustained over time (p < 0.0001). We conclude that
      simulation-based training significantly improves performance for at least 6-8
      weeks. Training should be repeated at intervals of 6 months or less.

PMID- 18336487
TI  - Laryngoscopy force in the sniffing position compared to the extension-extension
      position.
AB  - Laryngoscopy is sometimes easier with the patient's head and neck in the
      extension-extension position (head extension with the neck extended by the head
      section of the table bent down at 30 degrees) rather than the classical 'sniffing
      the morning air' position. We therefore tested the hypothesis that the axial
      force required for laryngoscopy is less in the extension-extension than the
      sniffing position. We measured the force axial to the handle of a Macintosh 3
      laryngoscope in 20 subjects under general anaesthesia who had been given
      neuromuscular blocking drugs. Measurement of force was made in the sniffing
      position and the extension-extension position. The mean (SD) axial force required
      in the extension-extension position was lower than in the sniffing position (19.6
      (7.8) N versus 23.6 (8.6) N, p = 0.04). In the setting of routine tracheal
      intubation, less force is required when the patient is in the extension-extension
      position than in the sniffing position.

PMID- 18336488
TI  - Retention of drug administration skills after intensive teaching.
AB  - We have identified deficiencies in medical students' drug administration skills,
      and we attempted to address them with interactive online teaching modules and
      simulated critical incident scenarios. Short-term improvements have been evident
      with this intensive effort, but medium-term retention of skills has not been
      measured. A drug administration lecture, an online module and a simulated
      emergency scenario were offered to final year clinical students. None of the
      teaching was compulsory but participation was recorded, along with students'
      simulator performances and marks in an objective structured practical examination
      9 months later. A poor simulator score predicted a poor performance in the later
      examination. Participation in the simulated scenario only significantly improved
      examination scores when supplemented by online teaching (p = 0.002). Intensive
      drug administration teaching using an online module and high fidelity simulation
      improves drug administration skills in the medium term. Students found simulation
      much more engaging than online teaching.

PMID- 18336489
TI  - Availability of lipid emulsion in obstetric anaesthesia in the UK: a national
      questionnaire survey.
AB  - There is evidence that administration of lipid emulsion improves outcome in
      cardiovascular collapse secondary to local anaesthetic toxicity. We sent a
      questionnaire to the lead consultant anaesthetist in every consultant-led labour
      ward in the UK asking about local guidelines for treatment of cardiac arrest, and
      whether or nor lipid emulsion was available on the labour ward and included in
      the guideline. We received replies from 195 (86%) labour wards. One hundred and
      seven (55%) reported having a guideline for the treatment of cardiovascular
      collapse secondary to local anaesthetic toxicity. Of these guidelines, lipid
      emulsion was included in 78 (40%). Lipid emulsion was readily available on 95
      labour wards (49%). Of the remaining units, there were plans to make lipid
      available in the near future in 46 (46%). Of the 95 labour wards where lipid
      emulsion was readily available, 80 (84%) had a recommended dose regimen for its
      administration. Around three-quarters of labour wards in the UK either have lipid
      emulsion available or plan to obtain it. This uptake should ideally be 100%.

PMID- 18336490
TI  - Peri-operative anaesthetic management of cytoreductive surgery with hyperthermic
      intraperitoneal chemotherapy.
AB  - Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a
      long and complex procedure with significant blood and fluid loss during debulking
      and important pathophysiological alterations during the HIPEC phase. We performed
      a retrospective analysis of 78 consecutive patients undergoing cytoreductive
      surgery with HIPEC at a university hospital. Our data demonstrate large intra
      operative fluid turnover, with 51% of patients requiring a blood transfusion.
      During HIPEC, airway pressure and central venous pressure increased with a lower
      oxygenation ratio as a result of increased intra-abdominal pressure with the
      closed abdomen technique. As a consequence of the raised body temperature, heart
      rate, end tidal carbon dioxide and arterial lactate levels increased with a
      slight metabolic acidosis. Peri-operative analysis of routine clotting parameters
      revealed disturbances of the coagulation status. For pain management, 72% of
      patients received supplementary thoracic epidural analgesia with consequential
      peri-operative opioid sparing and a reduced duration of postoperative
      ventilation.

PMID- 18336491
TI  - Metabolic acidosis in the critically ill: part 2. Causes and treatment.
AB  - The correct identification of the cause, and ideally the individual acid,
      responsible for metabolic acidosis in the critically ill ensures rational
      management. In Part 2 of this review, we examine the elevated (corrected) anion
      gap acidoses (lactic, ketones, uraemic and toxin ingestion) and contrast them
      with nonelevated conditions (bicarbonate wasting, renal tubular acidoses and
      iatrogenic hyperchloraemia) using readily available base excess and anion gap
      techniques. The potentially erroneous interpretation of elevated lactate
      signifying cell ischaemia is highlighted. We provide diagnostic and therapeutic
      guidance when faced with a high anion gap acidosis, for example pyroglutamate, in
      the common clinical scenario 'I can't identify the acid--but I know it's there'.
      The evidence that metabolic acidosis affects outcomes and thus warrants
      correction is considered and we provide management guidance including
      extracorporeal removal and fomepizole therapy.

PMID- 18336492
TI  - In vitro evaluation of the CeVOX continuous central venous oxygenation monitoring
      system.
AB  - We investigated the in vitro performance of the CeVOX system for continuous
      monitoring of central venous oxygen saturation by spectrophotometry (Pulsion
      Medical Systems, Munich, Germany). Oxygen inflow into the system was varied, and
      oxygen saturation values measured by CeVOX were documented. Blood samples were
      simultaneously taken to assess oxygen saturation by co-oximetry, and values were
      compared by Bland-Altman analysis. Sixty-six data pairs were obtained at CeVOX
      and co-oximetry values of 16-99% and 5.5-100%, respectively. Overall, CeVOX
      values only slightly overestimated co-oximetry values (mean bias +2.4%), but
      limits of agreement (2 SD of bias) were wide (-11.8 to +16.6%). Saturation
      measured by CeVOX underestimated that measured by co-oximetry at higher oxygen
      concentrations and overestimated it at lower oxygen concentrations. There was a
      nearly linear correlation of the mean bias, suggesting a systematic error. We
      conclude that the current version of the CeVOX system does not reliably reflect
      oxygen saturation.

PMID- 18336493
TI  - Measurement of tracheal wall pressure: a comparison of three different in vitro
      techniques.
AB  - We compared three different tracheal wall pressure measuring techniques in vitro.
      Using a high-volume, low-pressure, cuffed tracheal tube with an internal diameter
      of 7.5 mm and a model trachea, the pressure difference technique, the wall
      pressure membrane technique and the microchip sensor probe technique with and
      without lubrication were studied. Wall pressures were measured after sequential
      injections of 0.5 ml of air into the cuff at cuff pressures ranging from 0 to 50
      mmHg. The coefficient of variance was largest for the microchip sensor probe
      technique with lubrication (29%) and without lubrication (214%), and was lower
      for the wall pressure membrane technique (22%) and the pressure difference
      technique (19%). The wall pressure membrane and pressure difference techniques
      provided comparable results. The microchip sensor probe technique considerably
      underestimated wall pressure. These findings have an impact on the interpretation
      of published data on tracheal or pharyngeal wall pressure using the microchip
      sensor probe technique.

PMID- 18336494
TI  - Subarachnoid haematoma after spinal anaesthesia mimicking transient radicular
      irritation: a case report and review.
AB  - I report a patient with a spinal subarachnoid haematoma after difficult spinal
      anaesthesia who presented with symptoms of radicular irritation, and who
      recovered with conservative management. Subarachnoid haematoma is rare after
      spinal anaesthesia; a literature review found nine cases. In the majority of
      these cases, spinal anaesthesia had been difficult and unsuccessful. Other risk
      factors included antiplatelet and anticoagulant therapy, and direct spinal cord
      trauma. All the previous cases required decompressive laminectomy.

PMID- 18336495
TI  - Traumatic haemorrhage into an occult phaeochromocytoma: presentation and
      management in a patient with septic shock.
AB  - Phaeochromocytomas can have a variety of presentations; however, traumatic
      haemorrhage into a phaeochromocytoma is a rare presentation. Diagnosing and
      managing a critically ill, septic patient with a phaeochromocytoma can be very
      challenging. We report a case of a 57-year-old man, with a previously undiagnosed
      phaeochromocytoma, who presented initially with bowel perforation following an
      assault. Following a laparotomy for bowel resection and anastomosis, whilst on
      the intensive care unit, he developed paroxysmal severe hypertension overlying
      septic shock. Phaeochromocytoma was confirmed using a computed tomography scan
      and urinary assay of metanephrines and catecholamines. We managed the
      haemodynamic instability using labetalol and noradrenaline infusions. As his
      septic state improved he was started on conventional therapy and following
      control of his symptoms over the next few weeks, he underwent an uncomplicated
      right sided adrenalectomy. He made a full recovery.

PMID- 18336496
TI  - Intubation training in the real world.

PMID- 18336497
TI  - Intubation training in the real world.

PMID- 18336498
TI  - Intubation training in the real world.

PMID- 18336500
TI  - Calculating the volume of the oxygen reservoir bag for the Triservice anaesthetic
      apparatus.

PMID- 18336501
TI  - Hypertension and general anaesthesia: guidance for general practitioners and
      results of a questionnaire.

PMID- 18336502
TI  - Use of propofol in patients with food allergies.

PMID- 18336504
TI  - Nerve damage following the use of an i-gel supraglottic airway device.

PMID- 18336505
TI  - Tips for intubation with the Pentax-AWS Rigid Indirect Laryngoscope in morbidly
      obese patients.

PMID- 18336506
TI  - An unusual adverse reaction to tramadol.

PMID- 18336507
TI  - Length of spinal needles.

PMID- 18336508
TI  - Nasogastric tubes again. Another insertion tip: the throat pack.

PMID- 18336509
TI  - Glycaemic control in critically ill patients with myotonic dystrophy.

PMID- 18336515
TI  - Shortness of breath during dialysis--a role of bicarbonate in dialysis fluid?
AB  - Occasionally dialysis patients show symptoms that indicate intolerance in the way
      dialysis is delivered. This paper describes two cases of transient shortness of
      breath during the initial treatments after starting online haemodiafiltration
      (HDF). Our actions to deal with these symptoms focused on reducing the
      bicarbonate gain during the first phase of the dialysis treatment. As the
      symptoms gradually disappeared we hypothesise that the bicarbonate concentration
      in the dialysis fluid may play an important role for the development of shortness
      of breath and hypoxemia during HDF treatments.

PMID- 18336516
TI  - Relation of demographic, clinic and biochemical parameters to peritonitis in
      peritoneal dialysis.
AB  - The relation of various demographic, clinical and biochemical parameters of
      peritoneal dialysis patients with peritonitis and other infections was evaluated.
      The age, gender, peritoneal dialysis (PD) period, educational status,
      peritonitis, exit site score, serum albumin, C-reactive protein (CRP), and
      triglyceride levels at the beginning and the last visit were recorded. Mean age
      of 32 patients was 45.1 years; PD period was 13.1 months. Albumin level was
      inversely proportional to the frequency of peritonitis. Patients with peritonitis
      had albumin levels that were lower at the last visit, and were independent of the
      CRP values at the start of PD and during follow-up. Significant correlation was
      detected between females and exit site scores. There was significant correlation
      between educational status and peritonitis. Albumin level at first visit was a
      factor that reduced the likelihood of peritonitis, and low levels obtained during
      follow-up constituted a risk for peritonitis. It was also shown that peritonitis
      risk tended to decrease inversely with education level.

PMID- 18336517
TI  - Haemodialysis for children under the age of two years.
AB  - Less than 10% of children under 2 years old with end-stage renal failure in
      Europe and in the United States of America are treated with haemodialysis. For
      small children, peritoneal dialysis is often the preferred treatment.
      Haemodialysis is chosen for a very small number of children, and is only used in
      some selected centres because of its highly complex technique, the difficulties
      related to vascular access, and the need to have a skilled and experienced
      nursing and medical team. With the technological development of recent years, the
      quality of dialysis treatment offered to paediatric patients has improved
      considerably and haemodialysis is presently considered to be a safe and efficient
      treatment for acute or chronic paediatric renal impairment. However, because a
      successful renal transplant continues to be linked to a better quality of life
      for children with terminal chronic renal impairment, dialysis ought to be
      regarded as a temporary treatment method, while waiting for a renal transplant.

PMID- 18336518
TI  - The use of intradialytic parenteral nutrition in acutely ill haemodialysed
      patients.
AB  - BACKGROUND: Protein/caloric malnutrition is a problem in chronically
      haemodialysed patients, and is an independent risk factor for increased mortality
      in these patients. OBJECTIVES: To assess the safety and efficiency of
      intradialytic parenteral nutritional (IDPN) as nutritional support in acutely ill
      haemodialysis patients. METHODS: Twenty-two haemodialysis patients received IDPN
      after either major surgical or medical illnesses. Parameters measured included
      possible complications of IDPN, dialysis adequacy, patients' weight, protein
      catabolic rate (PCR) and serum levels of albumin, pre-albumin, creatinine,
      cholesterol, c-reactive protein (c-RP) and haemoglobin. After the end of the
      study all patients were followed-up for a further 6 months. RESULTS: Patients
      received IDPN for 1.5-48 months. Eighteen patients received IDPN <6 months. IDPN
      was safe for all patients. Throughout this period dialysis remained adequate.
      Weight loss in all patients ceased after approximately 2 months of IDPN. PRC,
      serum albumin, pre-albumin, cholesterol and creatinine levels all increased
      significantly. c-RP dropped from 77+/-86 mg/l to 9+/-10 mg/l. CONCLUSIONS: IDPN
      can be safely used in haemodialysed patients who are acutely ill and are unable
      to meet daily nutritional requirements with an oral intake. All studied
      parameters of nutrition and inflammation improved significantly while patients
      were treated with IDPN.

PMID- 18336519
TI  - Information topics important to chronic kidney disease patients: a systematic
      review.
AB  - It is essential to identify the information topics that are important to chronic
      kidney disease (CKD) patients to provide 'appropriate' information that will
      improve their knowledge, promote independence and encourage them to self-manage
      their illness. This paper, through a systematic review, explores the existing
      body of evidence on the information needs of CKD patients to identify information
      topic areas important to these patients and highlight factors that influence a
      patient's information needs.

PMID- 18336520
TI  - Nurse stress in hospital and satellite haemodialysis units.
AB  - AIM: To explore nurse stress in both in-centre hospital haemodialysis and
      satellite haemodialysis unit in an Australian city's health service. METHOD:
      Focus groups from both in-centre and satellite dialysis units were undertaken
      followed by questionnaires generated by the focus group data. RESULTS: In-centre
      nursing staff rated the busyness of the unit as the maximum stress and stated
      that they felt this high level of stress on a daily basis. The most notable
      stressor for the staff at the satellite unit related to patient behaviour and the
      perceived unrealistic expectations of the patient followed by patients arriving
      unwell at the unit. CONCLUSION: Nurses suffer stress on a daily basis in both in
      centre and satellite dialysis units. The major stressors differ from in-centre to
      satellite dialysis units.

PMID- 18336521
TI  - Noise and acoustics in renal units and hospitals [corrected].
AB  - The quality of the patient's life while in the hospital setting is important and
      hence the quality of the hospital environment is equally important. The effect of
      noise on health varies depending upon the susceptibility of the individual, but
      can include higher blood pressure, stress and annoyance in staff, and can erode
      quality of care. This paper ascertains what the noise levels are in a typical
      renal unit and considers the potential effects on staff and patients. The quality
      of the hospital environment plays an important part in treating patients
      effectively and efficiently. The use of acoustic design principles can reduce the
      level and impact of noise and, in doing so, improve the quality of care and the
      patient experience.

PMID- 18336522
TI  - New ways to approach the recruitment crisis in renal nursing in New South Wales,
      Australia.
AB  - As a strategy to counter the current crisis in staff recruitment and retention in
      dialysis nursing, a new model of care was designed to introduce Enrolled Nurses
      (EN) into what was previously almost exclusively a Registered Nurse (RN)
      workforce. The programme comprises training in medication administration
      conducted at the Technical and Further Education (TAFE) centre, training in
      dialysis procedures in the haemodialysis unit and clinical placement in the renal
      ward. Successful participants were recognised as Endorsed Enrolled Nurses, able
      to undertake extended roles in renal nursing care. A descriptive study was
      conducted. Nurses reported a high level of comfort, frequency, preparedness,
      confidence, competence and control. An audit of patient adverse events was also
      undertaken. Findings indicated no significant difference in patient admission
      rates, infection rates, and medication or procedure errors. In this article, the
      authors describe the design, implementation and evaluation of an educational
      programme for EN practicing in specialised haemodialysis services.

PMID- 18336523
TI  - The auxiliary table for GFR estimation according to the MDRD formula.
AB  - The best overall index of renal function is considered to be glomerular
      filtration rate (GFR) and the gold standard for its assessment is renal inulin
      clearance (Cin) Unfortunately, Cin cannot be routinely used in daily practice due
      to its complexity as a test. The most often used ones are the Cockcroft-Gault
      (CG) formula and the recently developed Modification of Diet in Renal Disease
      (MDRD) prediction equation. Calculation of MDRD (estimated GFR) according to this
      formula is simple but it requires a computer program. The following table is
      prepared for parts of the world where the computer program is not available as
      yet.

PMID- 18336524
TI  - Acceptance and rejection of dialysis--the need for patient evaluation.

PMID- 18336525
TI  - Cleavage and conformational changes of tau protein follow phosphorylation during
      Alzheimer's disease.
AB  - Phosphorylation, cleavage and conformational changes in tau protein all play
      pivotal roles during Alzheimer's disease (AD). In an effort to determine the
      chronological sequence of these changes, in this study, using confocal
      microscopy, we compared phosphorylation at several sites
      (Ser(199/202/396/404/422)-Thr(205) and the second repeat domain), cleavage of tau
      (D(421)) and the canonical conformational Alz-50 epitope. While all of these
      posttranslational modifications are found in neurofibrillary tangles (NFTs) at
      all stages of the disease, we found significantly higher numbers of phospho-tau
      positive NFTs when compared with cleaved tau (P = 0.006 in Braak III; P = 0.002
      in Braak IV; P = 0.012 in Braak V) or compared with the Alz-50 epitope (P <
      0.05). Consistent with these findings, in a double transgenic mice model (Tet/GSK
      3beta/VLW) overexpressing the enzyme glycogen synthase kinase-3beta (GSK-3beta)
      and tau with a triple FTDP-17 mutation (VLW) with AD-like neurodegeneration,
      phosphorylation at sites Ser(199/202)-Thr(205) was greater than truncated tau.
      Taken together, these data strongly support the notion that the conformational
      changes and truncation of tau occur after the phosphorylation of tau. We propose
      two probable pathways for the pathological processing of tau protein during AD,
      either phosphorylation and cleavage of tau followed by the Alz-50 conformational
      change or phosphorylation followed by the conformational change and cleavage as
      the last step.

PMID- 18336526
TI  - Bone repair in mandibular body osteotomy after using 2.0 miniplate system-
      histological and histometric analysis in dogs.
AB  - The objective of this study was to evaluate the bone repair along a mandibular
      body osteotomy after using a 2.0 miniplate system. Nine adult mongrel dogs were
      subjected to unilateral continuous defect through an osteotomy between the
      mandibular 3rd and 4th premolars. Two four-hole miniplates were placed in
      accordance with the Arbeitgeimeinschaft fur Osteosynthesefragen Manual.
      Miniplates adapted to the alveolar processes were fixed monocortically with 6.0
      mm-length titanium alloy self-tapping screws, whereas miniplates placed near the
      mandible bases were fixed bicortically. At 2, 6 and 12 weeks, three dogs were
      sacrificed per period, and the osteotomy sites were removed, divided into three
      thirds (Tension Third, TT; Intermediary Third, IT; Compression Third, CT) and
      prepared for conventional and polarized light microscopy. At 6 weeks, while the
      CT repaired faster and showed bone union by woven bone formation, the TT and IT
      exhibited a ligament-like fibrous connective tissue inserted in, and connecting,
      newly formed woven bone overlying the parent lamellar bone edges. At 12 weeks,
      bone repair took place at all thirds. Histometrically, proportions of newly
      formed bone did not alter at TT, IT and CT, whereas significantly enhanced bone
      formation was observed for the 12-week group, irrespective of the third. The
      results demonstrated that although the method used to stabilize the mandibular
      osteotomy allowed bone repair to occur, differences in the dynamics of bone
      healing may take place along the osteotomy site, depending on the action of
      tension and compression forces generated by masticatory muscles.

PMID- 18336527
TI  - Secretion of collagen I and tenascin is modulated by laminin-111 in 3D culture of
      human adenoid cystic carcinoma cells.
AB  - Adenoid cystic carcinoma is a frequent malignant salivary gland neoplasm with
      high levels of recurrence and metastasis. This neoplasm expresses prominent
      extracellular matrix (ECM). We are studying regulatory mechanisms underlying
      secretion of ECM molecules in adenoid cystic carcinoma. We have previously
      demonstrated that laminin modulates the phenotype of a human adenoid cystic
      carcinoma (CAC2) cell line. Thus, this molecule would be a good candidate to
      regulate secretion of ECM molecules in these cells. Here we analysed the role
      played by laminin-111 [formerly laminin-1; Aumailley et al. (2005). Matrix Biol.
      24, 326] stimulating secretory activity of CAC2 cells. Three-dimensional cultures
      of cells in laminin-111 (treated) or agarose (controls) were studied by light and
      electron microscopy. Ultrastructural analysis of CAC2 cells grown within laminin
      111 showed pseudocysts filled with secretory-like material. Cells exhibited
      prominent and dilated endoplasmic reticulum and coated and uncoated vesicles.
      Ultrastructural findings suggested that laminin-111 induced secretory activity in
      CAC2 cells. We further investigated this point by light microscopy,
      immunofluorescence and confocal microscopy. Histochemistry showed periodic acid
      Schiff (PAS)-positive diastase-resistant material in CAC2 cells treated by
      laminin-111. This material could represent laminin-induced secretion of ECM
      molecules. We searched for collagen I and tenascin in CAC2 cells treated by
      laminin-111. Confocal microscopy and immunoblot showed that laminin-111 enhanced
      secretion of collagen I and tenascin in CAC2 cells. We suggest that laminin-111
      modulates secretion of collagen I and tenascin in cells derived from human
      adenoid cystic carcinoma.

PMID- 18336528
TI  - Expression and arrangement of extracellular matrix proteins in the lungs of mice
      infected with Paracoccidioides brasiliensis conidia.
AB  - Extracellular matrix (ECM) proteins are important modulators of migration,
      differentiation and proliferation for the various cell types present in the
      lungs; they influence the immune response as well as participate in the adherence
      of several fungi including Paracoccidioides brasiliensis. The expression,
      deposition and arrangement of ECM proteins such as laminin, fibronectin,
      fibrinogen, collagen and proteoglycans in the lungs of mice infected with P.
      brasiliensis conidia has been evaluated in this study, together with the elastic
      fibre system. Lungs of BALB/c mice infected with P. brasiliensis conidia were
      analysed for the different ECM proteins by histological and immunohistochemical
      procedures at different times of infection. In addition, laser scanning confocal
      microscopy and scanning electron microscopy were used. During the early periods,
      the lungs of infected animals showed an inflammatory infiltrate composed mainly
      of polymorphonuclear neutrophils (PMNs) and macrophages, while during the later
      periods, mice presented a chronic inflammatory response with granuloma formation.
      Re-arrangement and increased expression of all ECM proteins tested were observed
      throughout all studied periods, especially during the occurrence of inflammatory
      infiltration and formation of the granuloma. The elastic fibre system showed an
      elastolysis process in all experiments. In conclusion, this study provides new
      details of pulmonary ECM distribution during the course of
      paracoccidioidomycosis.

PMID- 18336529
TI  - Enhanced proliferation of aortal smooth muscle cells treated by 1,25(OH)2D3 in
      vitro coincides with impaired formation of elastic fibres.
AB  - Elastin is the major extracellular matrix component synthesized, secreted and
      deposited by vascular smooth muscle cells (SMCs) in the arterial media and thus
      plays an important role in vascular homeostasis. Results of our previous studies
      showed that 1alpha,25-dihydroxycholecalciferol [1,25(OH)(2)D(3)-calcitriol]
      accelerates proliferation of SMCs and modulates their growth in vitro. The aim of
      this study was to find ultrastructural support for the idea that 1,25(OH)(2)D(3)
      calcitriol affects elastic fibre formation due to accelerated proliferation of
      aortal SMCs in vitro. SMCs exposed 10 days to supraphysiological concentration
      (10 nM) of calcitriol in primary culture were examined by fluorescence and
      transmission electron microscopy. Morphological studies revealed that calcitriol
      altered elastin maturation by favouring accumulation of immature rather than
      fully processed elastic fibres. A substantial decrease in the amorphous elastin
      deposition and abnormal accumulation of microfibrillar component, in thickened
      multilayer culture, were observed. These studies suggest that 1,25(OH)(2)D(3)
      affect formation of elastic fibres due to enhanced proliferation of SMCs in
      culture.

PMID- 18336530
TI  - Dysregulation of matrix metalloproteinases and their tissue inhibitors is related
      to abnormality of left ventricular geometry and function in streptozotocin
      induced diabetic minipigs.
AB  - This study aimed to characterize matrix metalloproteinases (MMPs) and their
      tissue inhibitors (TIMPs) in relation to changes in left ventricle (LV) geometry
      and function in a porcine model with streptozotocin (STZ)-induced diabetes. In 15
      Chinese Guizhou minipigs with STZ-induced diabetes (diabetic group) and 15 age
      matched normal controls (control group), Doppler tissue imaging was performed at
      6 months of diabetes. Serum MMP-2, -9, TIMP-1, -4 and B-type natriuretic peptide
      (BNP) were determined. Expression of MMPs, TIMPs, urokinase type-plasminogen
      activator (uPA), its receptor (uPAR) and plasminogen activator inhibitor-1 (PAI
      1) in aortic intima and LV myocardium was evaluated, with gelatinolytic
      activities of tissue MMP-2, -9 accessed by zymography. Left ventricle end
      diastolic septum thickness (P < 0.05) and mass (P < 0.05) were increased, whereas
      peak systolic mitral annulus velocity (Sm, P < 0.001), LV systolic (P = 0.01) and
      diastolic strain (P < 0.001) were significantly decreased in diabetic group than
      in controls. Diabetic group showed higher expression of TIMP-1, -4 in aortic
      intima and LV myocardium (P < 0.01 or P < 0.05), with increased collagen content
      and elevated serum BNP level (P = 0.004) and lower gelatinolytic activities of
      tissue MMP-2, -9 (all P < 0.05). Semi-quantitative RT-PCR of those diabetic
      tissues revealed elevated mRNA levels of major TIMPs, uPA, uPAR and PAI-1.
      Reduction of serum MMP-2 and -9 levels was observed in diabetic group vs. control
      group (both P < 0.05). This study features elevated levels of TIMP-1, -4, uPA,
      uPAR and PAI-1, and decreased activities of MMP-2, -9 in aorta and myocardium in
      STZ-induced diabetic minipigs, indicating that MMP-TIMP dysregulation is
      associated with LV hypertrophy, cardiac dysfunction and increased cardiovascular
      fibrosis in diabetes.

PMID- 18336531
TI  - The haemotoxicity of azathioprine in repeat dose studies in the female CD-1
      mouse.
AB  - Azathioprine (AZA) is a cytotoxic immunosuppressive drug used in the prevention
      of rejection in organ transplants and the treatment of auto-immune diseases.
      However, AZA is haemotoxic causing significant bone marrow depression. The
      present studies were to characterize the haemotoxicity of AZA in the female CD-1
      mouse. In Experiment 1, a dose-ranging study, with AZA gavaged daily for 10 days,
      clinical evidence of toxicity was evident at 125 mg/kg and above. Experiment 2
      was a dose-response study with AZA gavaged daily for 10 days at 40-120 mg/kg. At
      day 1 after the final dose, AZA induced a dose-related pancytopaenia, reduced
      femoral marrow cellularity, increases in serum levels of the cytokine fms-like
      tyrosine kinase 3 ligand, reduction in granulocyte-monocyte colony-forming units
      and erythroid colonies, and increased bone marrow apoptosis. Histology
      demonstrated hepatocyte hypertrophy, thymic atrophy, reduced splenic
      extramedullary haemopoiesis, and reduced cellularity of sternal bone marrow. In
      Experiment 3, AZA was dosed for 10 days at 100 mg/kg with autopsies at 1, 3, 9,
      22, 29, 43 and 57 days postdosing. At 1, 3 and 9 days, haematological parameters
      reflected changes in Experiment 2. At 22/29 days, many blood parameters were
      returning towards normal; at 43/57 days, most parameters compared with controls.
      However, there was some evidence of a persistent (i.e. residual/late-stage) mild
      reduction in RBC and erythroid progenitor cell counts at day 43/57. We conclude
      that the CD-1 mouse provides an acceptable model for the haemotoxicity of AZA in
      man.

PMID- 18336532
TI  - Serum FLT-3 ligand in a busulphan-induced model of chronic bone marrow hypoplasia
      in the female CD-1 mouse.
AB  - The concentration of the cytokine fms-like tyrosine kinase-3 ligand (FL) is
      elevated in the plasma of patients treated with chemotherapy or radiotherapy for
      malignant conditions. In addition, plasma FL is increased in patients with bone
      marrow failure resulting from stem-cell defects (e.g. aplastic anaemia). Our goal
      in the present study was to measure the concentration of serum FL in mice treated
      with the chemotherapeutic agent busulphan (BU) to induce bone marrow depression
      and relate changes in FL to effects on haemopoiesis. Female CD-1 mice were
      treated with BU (9.0 mg/kg) or vehicle by intraperitoneal injection on 10
      occasions over 21 days. Animals were autopsied on days 1, 23, 72, 119 and 177
      postdosing. A full blood count was performed, and serum prepared for FL analysis.
      Femoral marrow cell suspensions were prepared to assess the total femoral
      nucleated cell count (FNCC) and the number of committed haemopoietic progenitor
      cells (CFU-C). On days 1 and 23 postdosing, significant decreases were evident in
      many peripheral blood parameters; the FNCC and CFU-C were also reduced in BU
      treated mice, in conjunction with increases in serum FL levels. On days 72, 119
      and 177 postdosing, several peripheral blood and bone marrow parameters remained
      reduced and the concentration of serum FL continued to be significantly
      increased. Linear regression analysis demonstrated significant correlations
      between the concentration of serum FL in BU-treated mice and peripheral blood and
      bone marrow parameters; this suggests the possible use of serum FL as a potential
      biomarker for drug-induced bone marrow injury.

PMID- 18336533
TI  - How free of tobacco smoke are 'smoke-free' homes?
AB  - The risks of exposure to environmental tobacco smoke (ETS) are well established
      and 'harm reduction' strategies such as smoking outside to protect infants and
      children from exposure to ETS have been advocated for some time. The aim of this
      study was to assess the validity of self-reported smoking levels in residential
      settings. The participants were families (n = 92) randomly selected from lower
      socioeconomic areas of Perth, Western Australia. Each household was monitored for
      vapor phase nicotine and particulates with an aerodynamic diameter of < or = 10
      microm (PM(10)). Of the 42% (39) households who reported that someone smoked
      cigarettes at home, only four (4%) said that smoking occurred inside the house.
      There was a 'moderate' agreement between parental-reported tobacco smoking and
      levels of nicotine (kappa = 0.55, P < 0.01). There were significant differences
      in the median levels of air nicotine (P < 0.01) and PM(10) (P < 0.05) between
      households in which smoking was reported as only occurring outside, and the smoke
      free households. PRACTICAL IMPLICATIONS: The study outcome suggests that a
      strategy based on the separation of children and smoking activity is inadequate
      to protect the former from ETS at home, and that health professionals should give
      parents unambiguous advice to give up smoking in order to make their homes a
      completely smoke-free environment.

PMID- 18336534
TI  - Particle loading rates for HVAC filters, heat exchangers, and ducts.
AB  - The rate at which airborne particulate matter deposits onto heating, ventilation,
      and air-conditioning (HVAC) components is important from both indoor air quality
      (IAQ) and energy perspectives. This modeling study predicts size-resolved
      particle mass loading rates for residential and commercial filters, heat
      exchangers (i.e. coils), and supply and return ducts. A parametric analysis
      evaluated the impact of different outdoor particle distributions, indoor emission
      sources, HVAC airflows, filtration efficiencies, coils, and duct system
      complexities. The median predicted residential and commercial loading rates were
      2.97 and 130 g/m(2) month for the filter loading rates, 0.756 and 4.35 g/m(2)
      month for the coil loading rates, 0.0051 and 1.00 g/month for the supply duct
      loading rates, and 0.262 g/month for the commercial return duct loading rates.
      Loading rates are more dependent on outdoor particle distributions, indoor
      sources, HVAC operation strategy, and filtration than other considered
      parameters. The results presented herein, once validated, can be used to estimate
      filter changing and coil cleaning schedules, energy implications of filter and
      coil loading, and IAQ impacts associated with deposited particles. PRACTICAL
      IMPLICATIONS: The results in this paper suggest important factors that lead to
      particle deposition on HVAC components in residential and commercial buildings.
      This knowledge informs the development and comparison of control strategies to
      limit particle deposition. The predicted mass loading rates allow for the
      assessment of pressure drop and indoor air quality consequences that result from
      particle mass loading onto HVAC system components.

PMID- 18336535
TI  - Association between polymorphisms in the prostate-specific antigen (PSA) promoter
      and release of PSA.
AB  - Variations in serum prostate-specific antigen (PSA) have been ascribed to A/G
      nucleotide polymorphisms located at -158 bp (rs266882) and -4643 bp (rs925013),
      relative to the transcription start site within the promoter of the PSA gene. PSA
      is also an androgen receptor target (AR) gene and polymorphisms in AR gene are
      known to affect AR function. Our objective was to compare the impact of these A/G
      polymorphisms separately or in combination with AR CAG micro satellite on
      regulation of PSA secretion into seminal plasma and blood in young men. Leukocyte
      DNA was extracted from 291 conscripts and genotyping performed with the Sequenom
      Mass Array System. PSA was measured with an immunofluorometric assay. Linear
      regression analysis was used to test the association of polymorphism frequencies
      with serum and seminal plasma levels of PSA. PSA gene polymorphisms at -158 bp or
      -4643 bp did not alone influence total PSA (tPSA) levels in seminal plasma or in
      blood. Homozygotes for the A-allele at -158 bp in combination with CAG > 22 had
      significantly higher serum levels of tPSA than subjects carrying the G-allele (p
      = 0.01). In conclusion, the PSA gene polymorphisms did not importantly influence
      the levels of tPSA in seminal plasma or in blood. tPSA in serum was influenced by
      interactions between PSA promoter variants and AR CAG polymorphism.

PMID- 18336536
TI  - Rates of orchiopexies in Sweden: 1977-1991.
AB  - Cryptorchidism is a known risk factor for testicular cancer and the secular
      increase in testicular cancer incidence might have been paralleled by a similar
      increase in cryptorchidism. Data on trends in prevalence of cryptorchidism are
      however conflicting and decreases have recently been reported. To analyse Swedish
      trends in rates of orchiopexy, we used the Swedish Hospital Discharge Register to
      identify all cases of orchiopexy carried out for cryptorchidism between 1977 and
      1991, that is, before the era of outpatient orchiopexies in Sweden. Observed
      trends were analysed in 5-year age groups. The estimated average annual per cent
      changes (EAPCs) and the years in which the EAPC significantly changed were
      estimated using Joinpoint Regression. Finally, we estimated the cumulative
      incidence of orchiopexy by birth cohort. Among boys aged less than 10, the
      orchiopexy rate started to decrease in the early 1980s. EAPCs were -2.88 (95%
      confidence interval (CI): -5.48, -0.21) among boys aged 5-9 and -6.63 among those
      aged 0-4 (95% CI: -8.84, -4.37). Among subjects aged at least 10, the rate
      decreased over the whole study period. Although the use of orchiopexy rates to
      measure prevalence of cryptorchidism has limitations, our findings may suggest
      that cryptorchidism prevalence decreased in Sweden starting from the early 1980s.

PMID- 18336537
TI  - The hypothalamus-pituitary-testis axis in boys during the first six months of
      life: a comparison of cryptorchidism and hypospadias cases with controls.
AB  - It is inconclusive whether the feedback mechanisms of the hypothalamus-pituitary
      testis (HTP) axis are already established in the first 6 months of life, partly
      due to the dramatic changes in HPT-axis hormone levels over this period.
      Moreover, it is unclear whether these hormone levels are aberrant in boys with
      cryptorchidism or hypospadias, and therefore predictive for future fertility. We
      studied the regulation mechanisms of the HTP axis, and the effect of age, in boys
      1-6 months of age. Secondly, we studied testicular function - as reflected by HPT
      hormones - in newborns with cryptorchidism or hypospadias. Sera from a population
      sample of infants with cryptorchidism (n = 43), hypospadias (n = 41) and controls
      (n = 113) were analyzed for inhibin B, anti-Mullerian hormone (AMH),
      testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and
      sex hormone binding globulin (SHBG). LH, testosterone, non-shbg-bound
      testosterone (NSBT), and AHM levels showed significant age-related trends. After
      age-correction, a negative correlation between FSH and inhibin B was observed (r
      = -0.43). The only significant group-differences were lower testosterone and NSBT
      levels in cryptorchidism cases, with a mean testosterone of 1.8 and 2.6 nmol/L
      and a mean NSBT of 0.48 and 0.70 nmol/L for cryptorchidism cases and controls,
      respectively. The higher levels of LH, testosterone, and NSBT in boys born pre
      term or with a low birthweight indicate that abnormal prenatal development may
      determine postnatal testis function. Our results support the hypothesis that the
      inhibin B - FSH feedback loop is already functional before puberty. The lower
      testosterone and NSBT levels indicate that disturbed Leydig cell function can
      already be detected early after birth in cryptorchid boys.

PMID- 18336538
TI  - Infliximab in severe active ankylosing spondylitis with spinal ankylosis.
AB  - BACKGROUND: Infliximab is an anti-tumour necrosis factor monoclonal antibody,
      which significantly improves pain, stiffness and functional disability outcomes
      in patients with active ankylosing spondylitis. There are limited data available
      on the efficacy of this treatment for the subgroup with established spinal
      ankylosis. AIM: To compare the treatment response of infliximab in active severe
      ankylosing spondylitis for patients with and without radiographic evidence of
      spinal ankylosis in the clinical practice setting. METHODS: Twenty-seven patients
      with mean Bath Ankylosing Spondylitis Disease Activity Index of 8.7, all HLA-B27
      positive, with 11 (41%) having spinal ankylosis, were studied for 54 weeks. The
      qualification for initial and ongoing infliximab treatment was defined by the
      Australian Pharmaceutical Benefit Schedule (PBS), and 5 mg/kg of infliximab was
      given at 0 week (baseline), repeated at 2 and 6 weeks and every 6 weeks
      thereafter. At each time point, PBS-mandated and international consensus response
      measures were completed. Disease activity and outcome measures for spinal
      ankylosis subgroup and those who did not have spinal ankylosis were cross
      sectionally compared at baseline and 1 year. RESULTS: Patients with spinal
      ankylosis tended to be older (P = 0.01). Although the subgroup with spinal
      ankylosis had higher baseline activity scores, the only significant difference
      between the subgroups was the degree of morning stiffness (P = 0.04). By 54
      weeks, all patients including the subgroup with spinal ankylosis fulfilled the
      PBS criteria for continuation of treatment. Majority of patients including the
      subgroup with spinal ankylosis achieved the various international consensus
      response measures. Patients with spinal ankylosis also experienced significant
      improvements in health-related quality of life, with majority returning to full
      time employment by 1 year. CONCLUSION: In real-life clinical practice, patients
      with established disease with spinal ankylosis and high levels of inflammation
      and disease activity can achieve a major clinical response with infliximab.

PMID- 18336539
TI  - Methionine loading does not enhance the predictive value of homocysteine serum
      testing for all-cause mortality or major adverse cardiac events.
AB  - BACKGROUND: Hyperhomocysteinaemia is independently associated with
      atherosclerotic disease. Methionine loading could improve the predictive value of
      hyperhomocysteinaemia by detecting mild disturbances in enzyme activity. The aims
      of this study were to determine the beneficial effect of methionine loading on
      the predictive value of homocysteine testing for long-term mortality and major
      adverse cardiac events (MACE). METHODS: In an observational study, 1122 patients
      with suspected or known vascular disease, underwent homocysteine testing, which
      was measured fasting and again 6 h after methionine loading.
      Hyperhomocysteinaemia was defined as a fasting level > or =15 micromol/L and post
      methionine loading level > or =45 micromol/L or an increase of > or =30
      micromol/L above fasting levels. Primary end-points were death and MACE.
      Multivariate Cox regression analysis was used, adjusting for all cardiac risk
      factors. RESULTS: During follow up (mean 8.9 +/- 3.4 years), 98 patients died
      (8.7%), 86 had a MACE (7.7%), 579 patients had normal tests, 134 patients had
      only fasting hyperhomocysteinaemia, 226 only post-methionine
      hyperhomocysteinaemia and 183 patients had both. In multivariate analysis,
      overall survival and MACE-free survival were significantly worse for those with
      fasting hyperhomocysteinaemia, with hazard ratios of 1.86 (95% confidence
      interval (CI) 1.20-2.87) and 2.24 (95%CI 1.41-3.53), respectively. The addition
      of hyperhomocysteinaemia after methionine loading did not significantly increase
      the risk of death or MACE, with hazard ratios of 0.97 (95%CI 0.52-1.81) and 0.89
      (95%CI 0.47-1.69), respectively. CONCLUSION: The presence of post-methionine
      hyperhomocysteinaemia did not significantly alter risk of death or MACE in
      patients with normal or increased fasting homocysteine levels, respectively. In
      conclusion, methionine loading does not improve the predictive value of
      homocysteine testing with regard to long-term mortality or MACE.

PMID- 18336540
TI  - Autologous stem cell transplantation in diffuse scleroderma: impact on hand
      structure and function.
AB  - BACKGROUND: The aim of the study was to assess the structural and functional
      effects of autologous stem cell transplantation (ASCT) on scleroderma finger
      clawing. METHODS: Using photocopies of hands of five scleroderma patients who
      underwent ASCT using photocopies of hands. Functional assessments used a
      standardized questionnaire. RESULTS: Pre-ASCT, synovitis and tenosynovitis were
      present in five and four patients, respectively. Modified Rodnan hand skin scores
      ranged from 6-12/12. Following pulsed chemotherapy, synovitis resolved.
      Tenosynovitis often did not. Post-ASCT, skin scores fell in four patients (range
      0-6/12). Hand tenosynovitis resolved. With disease remission hand function
      globally improved. Functional improvement, noted early (+3 months) and
      continuously (+12 months) in disease remitters, occurred in all areas of
      function. Greatest hand-functional improvement related to paid employment,
      followed by self-care and hygiene, home-care activities and least by
      hobbies/sports. The second to fifth metacarpophalangeal width was reproducible
      and independent of ASCT therapy. In contrast, hand length and measures of
      abducted finger span (first to fifth fingertip and second to fifth fingertip
      distance) improved. Finger abduction (abducted first to fifth fingertips/second
      to fifth metacarpophalangeal width) was a more sensitive discriminator of finger
      clawing than hand length or hand length/second to fifth metacarpophalangeal
      width. CONCLUSION: ASCT improved hand scleroderma over 12 months and resolved
      previously refractory tenosynovitis. ASCT was unnecessary to treat scleroderma
      synovitis. ASCT secondarily improved hand function (paid employment, followed by
      self-care, home care, then by sport/hobbies). Loss of finger abduction was a more
      sensitive measure of finger clawing than apparent loss of hand length.

PMID- 18336541
TI  - Prevalence of the JAK2-V617F mutation in Taiwanese patients with chronic
      myeloproliferative disorders.
AB  - BACKGROUND: The Janus kinase-2 (JAK-2) V617F mutation has been recently reported
      in patients with myeloproliferative disorders (MPD), which is believed to
      underlie growth factor hypersensitivity displayed by haematopoietic progenitors
      in these disorders. However, its frequency has been rarely determined in
      Taiwanese patients. METHODS: The frequency of JAK2-V617F mutation in patients
      with polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis
      (IMF) was determined in the DNA from the peripheral blood leucocytes of 108
      patients by genomic polymerase chain reaction and restriction enzyme-based assay.
      RESULTS: The JAK2-V617F mutation could be detected in 28 of 33 polycythaemia vera
      patients (85%), 29 of 49 essential thrombocythaemia patients (59%) and 2 of 6 IMF
      patients (33%), but was not detected in 11 patients with myelodysplastic syndrome
      or another 10 with other haematological diseases. The presence of the JAK2
      mutation was associated with specific MPD disease subtypes (P = 0.007), longer
      disease duration (P = 0.005), splenomegaly (P = 0.019), a higher white blood cell
      count (P = 0.002) and a higher haemoglobin level (P = 0.036). However, the
      overall risk of thrombosis or bleeding was not affected by the presence of the
      JAK2 mutation (32 vs 17%; P = 0.22). CONCLUSION: The JAK2-V617F mutation can be
      frequently detected in the Taiwanese patients with MPD disorders and therefore
      should be incorporated into the initial evaluation of patients suspected of MPD.

PMID- 18336542
TI  - Provision of information on regulatory authorities' websites.
AB  - BACKGROUND: Several organizations have raised concerns about the excessive
      secrecy maintained by regulatory authorities around the world, in particular in
      the European Union, France, UK, Canada and Australia. However, limited research
      has assessed the provision of information by regulatory authorities. This study
      aimed to assess the type and availability of information provided on the
      regulatory authorities' websites. METHODS: Regulatory authorities' websites in
      six countries (USA, Canada, UK, France, Australia and New Zealand) and at the
      European level (European Medicines Evaluation Agency) were surveyed by two
      reviewers between October 2005 and March 2006. The survey instrument included 16
      criteria organized in 3 domains: information on marketed drugs, information on
      assessment of drugs and information on drug safety. RESULTS: There was a great
      variability in the level of information provided. Several medicine agencies did
      not provide basic information on marketed drugs, such as the summary of products'
      characteristics. Information on registration dossiers was scant on most websites
      except that of the US Food and Drug Administration. The European Medicines
      Evaluation Agency, the French agency and the Canadian agency released public
      assessment reports that contained only summarized information of registration
      data. Only one country, Canada, provided full access to pharmacovigilance data.
      The periodic safety update reports that companies have to provide regularly to
      regulatory authorities were not available in any country. CONCLUSION: Information
      on which regulatory authorities base their decisions for licensing new drugs and
      the rationales behind these decisions were often not publicly available.

PMID- 18336543
TI  - Association between waist-to-hip ratio and chronic kidney disease in the elderly.
AB  - BACKGROUND: To compare the anthropometric indices of obesity and identify which
      index serves as a better discriminator in the chronic kidney disease (CKD) for
      the elderly. METHODS: Participants of a 1-day health check, older than 60 years,
      in our hospital from 2003 to 2005 were enrolled. CKD was defined as estimated
      glomerular filtration rate by modification of diet in renal disease formula less
      than 60 mL/min per 1.73 m(2). Indices of obesity include body mass index, waist
      circumference, waist-to-hip ratio (WHR) and waist-to-height ratio. Traditional
      risk factors including diabetes, hypertension and metabolic syndrome were also
      taken into consideration. The accuracy of indices of obesity in predicting CKD
      was measured by area under the receiver operating characteristic curve (AUC).
      Association between risk factors was estimated by multivariate logistic
      regression. RESULTS: We studied 984 participants (537 men and 447 women) with a
      mean age of 66.7 +/- 5.3 years. A total of 161 (16.4%) participants was found
      having CKD. In the indices of obesity, WHR showed best diagnostic accuracy in
      predicting CKD (AUC: 0.58). A WHR cut-off value of 0.88 had a sensitivity of
      68.9% and a specificity of 45.4%. The odds ratios were significant for WHR,
      hypertension and diabetes (P = 0.025, P < 0.001 and P = 0.033). CONCLUSION: In
      indices of obesity, WHR is better than body mass index, bodyweight and waist
      circumferences in predicting CKD in elder Taiwanese. Furthermore, the association
      of WHR and CKD is independent of hypertension and diabetes.

PMID- 18336544
TI  - Synergistic premalignant effects of chronic ethanol exposure and insulin receptor
      substrate-1 overexpression in liver.
AB  - AIM: Insulin receptor substrate, type 1 (IRS-1) transmits growth and survival
      signals, and is overexpressed in more than 90% of hepatocellular carcinomas
      (HCCs). However, experimental overexpression of IRS-1 in the liver was found not
      to be sufficient to cause HCC. Since chronic alcohol abuse is a risk factor for
      HCC, we evaluated potential interactions between IRS-1 overexpression and chronic
      ethanol exposure by assessing premalignant alterations in gene expression.
      METHODS: Wild-type (wt) or IRS-1 transgenic (Tg) mice, constitutively
      overexpressing the human (h) transgene in the liver, were pair-fed isocaloric
      liquid diets containing 0% or 24% ethanol for 8 weeks. The livers were used for
      histopathologic study and gene expression analysis, focusing on insulin, insulin
      like growth factor (IGF) and wingless (WNT)-Frizzled (FZD) pathways, given their
      known roles in HCC. RESULTS: In wt mice, chronic ethanol exposure caused
      hepatocellular microsteatosis with focal chronic inflammation, reduced expression
      of proliferating cell nuclear antigen (PCNA) and increased expression of IGF-I
      and IGF-I receptor. In hIRS-1 Tg mice, chronic ethanol exposure caused hepatic
      micro- and macrosteatosis, focal chronic inflammation, apoptosis and disordered
      lobular architecture. These effects of ethanol in hIRS-1 Tg mice were associated
      with significantly increased expression of IGF-II, insulin, IRS-4, aspartyl
      asparaginyl beta hydroxylase (AAH), WNT-1 and FZD 7, as occurs in HCC.
      CONCLUSION: In otherwise normal liver, chronic ethanol exposure mainly causes
      liver injury and inflammation with impaired DNA synthesis. In contrast, in the
      context of hIRS-1 overexpression, chronic ethanol exposure may serve as a
      cofactor in the pathogenesis of HCC by promoting expression of growth factors,
      receptors and signaling molecules known to be associated with hepatocellular
      transformation.

PMID- 18336545
TI  - Mucoepidermoid carcinoma of the liver: report of a rare case and review of the
      literature.
AB  - Although a mucoepidermoid carcinoma is sometimes seen as a neoplasm originating
      from the salivary glands, its origination from the liver is rare. A review of the
      medical literature in the English language disclosed only 16 cases originating
      from the hepatic system. The case explored here is that of an 81-year-old female,
      without any significant medical history, who was referred to our hospital for
      elevated liver function tests. Computed tomography (CT) showed a huge tumor, 10
      cm in diameter, in the right lobe of the liver. The central part of the tumor was
      consistently un-enhanced, suggesting a large necrotic area. The liver tumor was
      diagnosed as mucoepidermoid carcinoma by a percutaneous biopsy. Despite
      chemotherapy with radiation therapy, the tumor showed very aggressive malignancy,
      resulting in early mortality. We herein report on a rare case of primary
      mucoepidermoid carcinoma of the liver with pulmonary and lymph node metastasis,
      confirmed by autopsy, and review the literature.

PMID- 18336546
TI  - Liver transplantation for factor XI deficiency: cure before diagnosis.

PMID- 18336547
TI  - Bifidobacterium microbiota and parameters of immune function in elderly subjects.
AB  - Faecal and serum samples were collected over a period of 6 months from 55
      institutionalized elderly subjects, who were enrolled in a double-blind placebo
      controlled study. Participants were randomized in one of the three treatment
      groups: intervention (two probiotic Bifidobacterium longum strains: 2C and 46),
      placebo and commercial control (Bifidobacterium lactis Bb-12). The faecal
      Bifidobacterium microbiota was characterized by genus and species-specific PCR.
      Serum levels of the cytokines IL-10, tumor necrosis factor (TNF)-alpha and
      transforming growth factor (TGF)-beta1 were determined by enzyme-linked
      immunosorbent assay. Each participant harboured on average approximately three
      different bifidobacterial species. The most frequently detected species were B.
      longum, Bifidobacterium adolescentis and Bifidobacterium bifidum. Depending on
      the treatment, the intervention resulted in specific changes in the levels of
      certain Bifidobacterium species, and positive correlations were found between the
      different species. Negative correlations were observed between the levels of
      Bifidobacterium species and the pro-inflammatory cytokine TNF-alpha and the
      regulatory cytokine IL-10. The presence of faecal B. longum and Bifidobacterium
      animalis correlated with reduced serum IL-10. The anti-inflammatory TGF-beta1
      levels were increased over time in all three groups, and the presence of
      Bifidobacterium breve correlated with higher serum TGF-beta1 levels. This
      indicates that modulation of the faecal Bifidobacterium microbiota may provide a
      means of influencing inflammatory responses.

PMID- 18336548
TI  - Strain selection for improvement of Bradyrhizobium japonicum competitiveness for
      nodulation of soybean.
AB  - A Bradyrhizobium japonicum USDA 110-derived strain able to produce wider halos in
      soft-agar medium than its parental strain was obtained by recurrent selection. It
      was more chemotactic than the wild type towards mannitol and three amino acids.
      When cultured in minimal medium with mannitol as a single carbon-source, it had
      one thick subpolar flagellum as the wild type, plus several other flagella that
      were thinner and sinusoidal. Root adsorption and infectivity in liquid media were
      50-100% higher for the selected strain, but root colonization in water
      unsaturated vermiculite was similar to the wild type. A field experiment was then
      carried out in a soil with a naturalized population of 1.8 x 10(5) soybean
      nodulating rhizobia g of soil(-1). Bradyrhizobium japonicum strains were
      inoculated either on the soybean seeds or in the sowing furrows. Nodule
      occupation was doubled when the strains were inoculated in the sowing furrows
      with respect to seed inoculation (significant with P<0.05). On comparing strains,
      nodule occupation with seed inoculation was 6% or 10% for the wild type or
      selected strains, respectively, without a statistically significant difference,
      while when inoculated in the sowing furrows, nodule occupation increased to 12%
      and 22%, respectively (differences significant with P<0.05).

PMID- 18336549
TI  - Isolation and characterization of an operon involved in sulfate and sulfite
      metabolism in Sinorhizobium fredii.
AB  - A gene cluster ORFabcd from a Sinorhizobium fredii HN01 mutant strain HSMRalpha
      was isolated. We showed that it was an operon involved in sulfur metabolism.
      Functional studies revealed that, except for ORFb, the three genes ORFa, ORFc and
      ORFd were involved in sulfite reduction. ORFa and ORFc were similar to the cysG
      and cysI from Sinorhizobium meliloti 1021 and Rhizobium etli CFN 42,
      respectively. ORFd encodes a conserved hypothetical protein in other bacteria. We
      demonstrate here, for the first time, that it was a new locus involved in sulfate
      assimilation in S. fredii HN01 and we designated it as cysII.

PMID- 18336550
TI  - A combined stress response analysis of Spirulina platensis in terms of global
      differentially expressed proteins, and mRNA levels and stability of fatty acid
      biosynthesis genes.
AB  - Changes in gene expression play a critical role in enhancing the ability of
      cyanobacteria to survive under cold conditions. In the present study, Spirulina
      platensis cultures were grown at the optimal growth temperature, in the light,
      before being transferred to dark conditions at 22 degrees C. Two dimensional
      differential gel electrophoresis was then performed to separate differentially
      expressed proteins that were subsequently identified by MS. Among all
      differentiated proteins identified, a protein involved in fatty acid
      biosynthesis, (3R)-hydroxymyristoyl-[acyl-carrier-protein]-dehydratase encoded by
      fabZ, was the most up-regulated protein. However, the fatty-acid desaturation
      proteins were not significantly differentiated. This raised the question of how
      the unsaturated fatty acid, especially gamma-linolenic acid, content in the cells
      in the cold-dark shift remained stable compared with that of the cold shift.
      Thus, a study at the transcriptional level of these desaturase genes, desC, desA
      and desD, and also of the fabZ gene was conducted. The results indicated that in
      the dark, where energy is limited, mRNA stability was enhanced by exposure to low
      temperatures. The data demonstrate that when the cells encounter cold stress with
      energy limitation, they can maintain their homeoviscous adaptation ability via
      mRNA stability.

PMID- 18336551
TI  - Highly polymorphic variable-number tandem repeats loci for differentiating
      Beijing genotype strains of Mycobacterium tuberculosis in Shanghai, China.
AB  - The PCR-based variable-number tandem repeats (VNTR) typing method is a very
      promising tool for the molecular epidemiological study of Mycobacterium
      tuberculosis. The discriminatory power of the VNTR loci that were optimized in
      many previous studies has not been evaluated in Shanghai, an area where Beijing
      genotype strains dominate. In the present study, we first performed a literature
      search to identify VNTR loci that were at least 45 bp in length. Second, we
      determined the Hunter-Gaston discriminatory index (HGI) values of each of the 45
      VNTR loci that we identified, using Beijing genotype strains from a 'test set' of
      isolates from a population with low migration in Chongming Island, Shanghai,
      China. Third, we optimized two sets of VNTR loci, which we named VNTR-7 and VNTR
      16. The HGI value of VNTR-7 was slightly lower than that of IS6110 restriction
      fragment length polymorphisms (RFLP), and the HGI values of VNTR-16 and IS6110
      RFLP were comparable. Our results suggest that VNTR-7, followed by VNTR-16 and
      IS6110 RFLP, can be used routinely as a tool to discriminate between M.
      tuberculosis isolates in population-based epidemiologic studies of M.
      tuberculosis transmission in Shanghai, China.

PMID- 18336552
TI  - The Saccharomyces cerevisiae Wss1 protein is only present in mother cells.
AB  - The Saccharomyces cerevisiae WSS1 (Weak Suppressor of Smt3) gene has initially
      been identified as a multicopy suppressor of a mutation in SMT3 encoding the
      small ubiquitin-like modifier. Later, multiple functions related to DNA
      replication and repair have been found for WSS1. Here, we report the subcellular
      location of the Wss1 protein. Fluorescence microscopy of strains expressing a
      Wss1p-green fluorescent protein (GFP) fusion shows that the protein is present in
      a single sharp spot near the nuclear membrane, distinct from the spindle pole
      bodies and nucleolus. In dividing cells, the spot is exclusively present in the
      mother cell, suggesting a mother cell-specific function of WSS1.

PMID- 18336553
TI  - Complete nucleotide sequence of a virulence plasmid of Salmonella enterica
      serovar Dublin and its phylogenetic relationship to the virulence plasmids of
      serovars Choleraesuis, Enteritidis and Typhimurium.
AB  - The complete nucleotide sequence of pOU1113 (pSDVu), one of the two types of
      virulence plasmids of Salmonella enterica serovar Dublin, was determined. It
      contained 80 156 bp with 53.8 mol% G+C content. Approximately 70 genes could be
      discerned. Compared with pSTV, the virulence plasmid of serovar Typhimurium,
      pOU1113 was shorter owing to a missing region amounting to c. 10 kb; furthermore,
      except for a unique 10 849-bp region, the nucleotide as well as deduced amino
      acid sequences of pOU1113 were nearly identical to the corresponding regions of
      three S. enterica virulence plasmids, namely pSCV (virulence plasmid of
      Choleraesuis), pSTV and pSEV (virulence plasmids of Enteritidis), confirming
      their close phylogenetic relationship. Comparative analysis indicated that these
      virulence plasmids appeared to have descended by deletion from a relatively large
      plasmid to smaller ones, with some recombination events occurring over time. From
      a biological and evolutionary point of view, if the decreasing sizes of pOU1113
      and pSCV truly reflect a process in which the virulence plasmid has been shedding
      unnecessary genes during evolution, our data suggest that some genes in the
      missing region, such as the pef and tra operons, could have a minimal role in
      maintaining the survival of the bacteria in their environmental niche.

PMID- 18336554
TI  - Endophytic colonization of olive roots by the biocontrol strain Pseudomonas
      fluorescens PICF7.
AB  - Confocal microscopy combined with three-dimensional olive root tissue sectioning
      was used to provide evidence of the endophytic behaviour of Pseudomonas
      fluorescens PICF7, an effective biocontrol strain against Verticillium wilt of
      olive. Two derivatives of the green fluorescent protein (GFP), the enhanced green
      and the red fluorescent proteins, have been used to visualize simultaneously two
      differently fluorescently tagged populations of P. fluorescens PICF7 within olive
      root tissues at the single cell level. The time-course of colonization events of
      olive roots cv. Arbequina by strain PICF7 and the localization of tagged bacteria
      within olive root tissues are described. First, bacteria rapidly colonized root
      surfaces and were predominantly found in the differentiation zone. Thereafter,
      microscopy observations showed that PICF7-tagged populations eventually
      disappeared from the root surface, and increasingly colonized inner root tissues.
      Localized and limited endophytic colonization by the introduced bacteria was
      observed over time. Fluorescent-tagged bacteria were always visualized in the
      intercellular spaces of the cortex region, and no colonization of the root xylem
      vessels was detected at any time. To the best of our knowledge, this is the first
      time this approach has been used to demonstrate endophytism of a biocontrol
      Pseudomonas spp. strain in a woody host such as olive using a nongnotobiotic
      system.

PMID- 18336555
TI  - Diversity and spatio-temporal distribution of ammonia-oxidizing Archaea and
      Bacteria in sediments of the Westerschelde estuary.
AB  - The diversity and spatio-temporal distribution of ammonia-oxidizing Archaea (AOA)
      and Bacteria (AOB) were investigated along a salinity gradient in sediments of
      the Westerschelde estuary. Sediment samples were collected from three sites with
      different salinities, and at six time points over the year. Denaturing gradient
      gel electrophoresis of PCR-amplified 16S rRNA and amoA gene fragments was used to
      identify the AOA and AOB present. Members of the AOA were mainly belonging to the
      Crenarchaeota Group 1, which were found at all sites, while members of the genus
      Nitrosomonas, which were abundant at the brackish sites, and of the genus
      Nitrosospira, which were present in early spring at the marine sites, were found
      to be the dominant AOB. Statistical analysis indicated that salinity and
      temperature were the main factors controlling the diversity and distribution of
      both AOA and AOB. Variability in net primary production rates was also correlated
      with species composition of both groups, but changes in the nitrite concentration
      only to the distribution of the AOA.

PMID- 18336556
TI  - Genetic diversity in strains of the genus Anabaena isolated from planktonic and
      benthic habitats of the Gulf of Finland (Baltic Sea).
AB  - Late summer cyanobacterial blooms in the Baltic Sea contain Anabaena sp. together
      with Nodularia spumigena and Aphanizomenon flos-aquae. Although Anabaena is
      common especially in the Gulf of Finland, very little is known about its genetic
      diversity. Here we undertook a molecular phylogenetic study of 68 Anabaena
      strains isolated from the brackish Gulf of Finland. We sequenced the 16S rRNA
      genes from 54 planktonic and 14 benthic Anabaena strains, and rbcL and rpoC1
      genes from a subset of these strains. Phylogenetic trees showed that Anabaena
      strains, from both planktonic and benthic habitats, were genetically diverse.
      Although the Anabaena strains were morphologically diverse, in our study only one
      genetically valid species was found to exist in the plankton. Evolutionary
      distances between benthic Anabaena strains were greater than between planktonic
      strains, suggesting that benthic habitats allow for the maintenance of greater
      genetic diversity than planktonic habitats. A number of novel lineages containing
      only sequences obtained in this study were compiled in the phylogenetical
      analyses. Thus, it seemed that novel lineages of the genus Anabaena may be
      present in the Baltic Sea. Our results demonstrate that the Baltic Sea Anabaena
      strains show surprisingly high genetic diversity.

PMID- 18336557
TI  - Ecological advantages from light adaptation and heterotrophic-like behavior in
      Synechococcus harvested from the Gulf of Trieste (Northern Adriatic Sea).
AB  - A preliminary study was carried out on a picocyanobacterial mixed culture
      harvested from the Gulf of Trieste (Northern Adriatic) and identified as
      Synechococcus spp. both by transmission electron microscopy observations,
      biliprotein composition and molecular analyses. Absorption and fluorescence
      spectra revealed phycourobilin and phycoerythrobilin chromophores, suggesting the
      presence of both CU- and C-phycoerythrin, besides phycocyanobilin chromophores
      typical for phycocyanins and allophycocyanins. Both biliprotein analyses and
      molecular identification indicated the presence of at least two Synechococcus
      subgroups presumably differing either in phycoerythrin type or in physiological
      traits. Among the exoenzymatic activities acting on different substrates, only
      aminopeptidase showed high hydrolysis rates and the uptake of organic molecules
      was positive for leucine but not for thymidine. The protein carbon mobilized was
      high compared with the leucine incorporation rates, resulting in low percentages
      of newly mobilized carbon utilized by cultures. The organic carbon incorporated
      as leucine was compared with the photosynthetically produced one, and the balance
      between the phototrophic- and heterotrophic-like processes was c. 3 : 1. Our
      findings suggest that the Synechococcus heterotrophy plays an important role in
      cell's metabolism, and that the photoheterotrophic behavior, together with their
      chromatic adaptation capability, might represent the key for the absolute
      dominance of this genus in the Adriatic Sea.

PMID- 18336558
TI  - Effects of chronic treatment with valproate and oxcarbazepine on ovarian
      folliculogenesis in rats.
AB  - PURPOSE: We aimed to define the morphologic effects of valproate (VPA) and
      oxcarbazepine (OXC) on ovarian folliculogenesis in rats. METHODS: Forty female
      wistar rats (21-24 days old and weighted between 46.4 and 55.3 g) were divided
      equally into 4 experimental groups, which were applied tap water (control group),
      300 mg/kg/day VPA, 100 mg/kg/day OXC, and both VPA and OXC via gavage for 90
      days. Ovaries of the rats on proestrous and diesterous phase of estrous cycle
      according to daily vaginal smear were taken out and placed in a fixation
      solution. Immunohistochemical and apoptosis (TUNEL) staining protocols were
      applied. RESULTS: The number of follicles decreased and that of corpora lutea
      increased significantly in OXC, VPA, and OXC+VPA treated groups compared with
      control group (p < 0.05). The number of TUNEL positive ovarian follicles was 1.40
      +/- 0.52 in control group, but it significantly increased to 3.50 +/- 0.53, 3.50
      +/- 0.53, and 4.90 +/- 0.88 in VPA, OXC, and VPA+OXC groups (p < 0.0001). The
      increase in the number of TUNEL positive granulosa cells was also significant for
      OXC and VPA+OXC groups (p < 0.0001). Immunohistochemical HSCORE decreased for TGF
      beta 1 and IGF1 staining and increased for P53 staining in all drug groups
      compared with control group (p < 0.001). Intensity of P53 labeling increased,
      while intensity of TGF beta 1, IGF-1, and GDF-9 immunoreactivity decreased
      significantly in all drug groups compared with control group (p < 0.001).
      CONCLUSION: Long-term treatment with VPA or OXC from prepuberty to adulthood
      causes apoptosis and deterioration of folliculogenesis in rat ovarian follicles.

PMID- 18336559
TI  - Seizures in multiple sclerosis.
AB  - Seizures have long been recognized to be part of the disease spectrum of multiple
      sclerosis (MS). While they occur in only a minority of patients with MS,
      epileptic seizures can have serious consequences. The treatment of MS can be
      epileptogenic, and antiepileptic treatment can conversely worsen the symptoms of
      MS. In this article we present an overview of the current literature on the
      epidemiology, clinical presentation, pathology, imaging, prognosis and treatment
      of epileptic seizures in MS.

PMID- 18336560
TI  - Estimating the incidence of first unprovoked seizure and newly diagnosed epilepsy
      in the low-income urban community of Northern Manhattan, New York City.
AB  - PURPOSE: To estimate the incidence and mortality associated with first unprovoked
      seizure or newly diagnosed epilepsy in a low-income, predominantly Hispanic
      community in Northern Manhattan, New York City. METHODS: We performed a
      population-based study to determine the incidence of first unprovoked seizure or
      newly diagnosed epilepsy. Participants were Northern Manhattan residents seen at
      area hospitals and nursing homes between 2003 and 2005. Cumulative probability of
      mortality and standardized mortality ratios (SMRs) were also calculated. RESULTS:
      Among 209 incident cases identified, 123 (58.9%) presented with an incident
      single unprovoked seizure. A total of 138 (66.0%) participants were Hispanic and
      94 (45.0%) had a median household income under $15,000/year. The overall age and
      sex-adjusted incidence of all unprovoked seizures was 41.1 (95%CI = 35.4-46.8)
      per 100,000 person-years. Higher incidence was observed in low-income groups.
      Incidence among Hispanics was similar to that of non-Hispanic whites and non
      Hispanic blacks. The cumulative probability of mortality was 17% (95%CI = 12-24%)
      by 3 years after diagnosis and was significantly greater in females and in those
      with an identified etiology. SMRs were significantly increased for all groups
      with respect to age, Hispanic ethnicity, middle and high income, partial seizure
      type, and remote symptomatic etiology. Idiopathic/cryptogenic and progressive
      symptomatic etiologies, low income, gender, and non-Hispanic ethnicity were not
      associated with a significantly increased SMR. CONCLUSION: Incidence of first
      unprovoked seizure or newly diagnosed epilepsy did not differ by race-ethnicity.
      Although lower income was associated with higher incidence, higher income was
      associated with an increased SMR. Future research should examine reasons for
      differential incidence by income.

PMID- 18336561
TI  - Ten testicular trapdoors.
AB  - Testicular pathology is difficult and there are a number of areas where
      diagnostic errors may lead to inappropriate treatment. We therefore describe ten
      areas of testicular pathology which may cause diagnostic confusion for
      pathologists: ten testicular trapdoors.

PMID- 18336562
TI  - Alkaptonuria--a review of surgical and autopsy pathology.
AB  - Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase
      that leads to the widespread deposition of polymeric homogentisic acid, and
      clinical symptoms from degeneration of joints and the aortic valve. Pathological
      descriptions are few and mainly those of late-stage changes related to joint or
      valve failure. In this review, the macroscopic and histopathological changes in
      the tissues in alkaptonuria are illustrated by the detailed autopsy study of a 74
      year-old female who died from disseminated ovarian carcinoma. The pathology is
      discussed in the context of the literature and in relation to potential
      pathogenic mechanisms of tissue damage. This review highlights the heterogeneity
      of some of the manifestations. In symptomatic patients, degenerative changes in
      synovial and intervertebral joints are usually well advanced, while early changes
      include diffuse cartilage pigmentation and chondrocyte necrosis. The initial
      stage of pigment deposition in the cardiovascular system may be influenced by
      intravascular pressure and flow disturbances, whereas more intense pigmentation
      affects fibrolipid components of atheromatous plaques. Pigmentation of the aortic
      and mitral valve cusps and valve rings is a result of intracellular and
      extracellular pigment deposition and is associated with calcification and
      clinically significant aortic stenosis.

PMID- 18336563
TI  - Abundance and composition of ammonia-oxidizing bacteria and ammonia-oxidizing
      archaea communities of an alkaline sandy loam.
AB  - The abundance and composition of soil ammonia-oxidizing bacteria (AOB) and
      ammonia-oxidizing archaea (AOA) communities under different long-term (17 years)
      fertilization practices were investigated using real-time polymerase chain
      reaction and denaturing gradient gel electrophoresis (DGGE). A sandy loam with pH
      (H(2)O) ranging from 8.3 to 8.7 was sampled in years 2006 and 2007, including
      seven fertilization treatments of control without fertilizers (CK), those with
      combinations of fertilizer nitrogen (N), phosphorus (P) and potassium (K): NP,
      NK, PK and NPK, half chemical fertilizers NPK plus half organic manure (1/2OMN)
      and organic manure (OM). The highest bacterial amoA gene copy numbers were found
      in those treatments receiving N fertilizer. The archaeal amoA gene copy numbers
      ranging from 1.54 x 10(7) to 4.25 x 10(7) per gram of dry soil were significantly
      higher than those of bacterial amoA genes, ranging from 1.24 x 10(5) to 2.79 x
      10(6) per gram of dry soil, which indicated a potential role of AOA in
      nitrification. Ammonia-oxidizing bacteria abundance had significant correlations
      with soil pH and potential nitrification rates. Denaturing gradient gel
      electrophoresis patterns revealed that the fertilization resulted in an obvious
      change of the AOB community, while no significant change of the AOA community was
      observed among different treatments. Phylogenetic analysis showed a dominance of
      Nitrosospira-like sequences, while three bands were affiliated with the
      Nitrosomonas genus. All AOA sequences fell within cluster S (soil origin) and
      cluster M (marine and sediment origin). These results suggest that long-term
      fertilization had a significant impact on AOB abundance and composition, while
      minimal on AOA in the alkaline soil.

PMID- 18336564
TI  - Activation of dopamine D1-like receptors in nucleus accumbens is critical for the
      acquisition, but not the expression, of nutrient-conditioned flavor preferences
      in rats.
AB  - The present study investigated the role of dopamine neurotransmission within the
      nucleus accumbens (NAc) in flavor preference learning induced by the postoral
      consequences of carbohydrates. In Experiment 1, rats fitted with a gastric
      catheter were trained with a flavor (CS+) paired with intragastric (IG) infusions
      of 8% glucose and a different flavor (CS-) paired with IG water infusions. The
      CS+ preference was then evaluated in two-bottle preference tests following
      bilateral injection of the dopamine D1-like receptor antagonist SCH23390 into the
      NAc shell at total doses of 0, 12, 24 and 48 nmol. SCH23390 produced dose-related
      reductions in CS+ intake but did not block the CS+ preference except at the
      highest dose, which also greatly suppressed the CS intakes. In Experiment 2, new
      rats were injected daily in the NAc shell with either saline or SCH23390 (12
      nmol), 10 min prior to training sessions with CS+ with IG glucose and CS- with IG
      water. In the two-bottle preference tests, the drug-treated rats, unlike the
      control rats, did not significantly prefer the CS+ (61 vs. 83% preference). In
      Experiment 3, new rats were trained with the same procedures as Experiment 2,
      except that brain injections were in the NAc core. In contrast to control rats,
      SCH-treated rats failed to prefer the CS+ to the CS- in two-bottle tests (55% vs.
      89% preference). These results demonstrate that D1-like receptors in the NAc
      shell and core are greatly involved in the acquisition, but less so in the
      expression, of a flavor preference conditioned by postingestive effects of
      glucose.

PMID- 18336565
TI  - Forebrain dopamine depletion impairs motor behavior in lamprey.
AB  - The structure of the basal ganglia appears to be conserved throughout vertebrate
      evolution, with characteristic cellular and transmitter components in each area,
      and the same types of afferent input. As described in rodents and primates,
      depletion of the striatal dopamine results in characteristic motor deficits. To
      explore if this role of the basal ganglia in modulating motor function was
      present early in vertebrate evolution, we investigated here the effects of
      striatal dopamine depletion in the lamprey, a cyclostome, which diverged from the
      main vertebrate line around 560 million years ago. The lamprey striatum contains
      the same cellular elements as found in mammals, and receives the same types of
      input, including a prominent dopamine innervation. We show here that MPTP (1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 100 mg/kg i.p.), a neurotoxin,
      depletes forebrain and striatal dopamine levels in lamprey to 15% of control
      values, and has profound effects on motor performance. Twenty-four and 48 h after
      MPTP injection, lampreys demonstrated marked reductions in spontaneous swimming
      and the duration of each swimming episode. Impairments in the ability to initiate
      movements were shown by a decreased rate of initiation. Furthermore, the
      initiation and maintenance of locomotion induced by olfactory mucosa stimulation
      was severely impaired, as was the coordination of different motor tasks. These
      deficits were ameliorated by the dopamine agonist apomorphine. The motor deficits
      arising after striatal dopamine depletion are thus qualitatively similar in
      cyclostomes and mammals. The role of the dopamine innervation of the striatum
      thus appears to be conserved throughout vertebrate evolution.

PMID- 18336566
TI  - Enhancement of long-range EEG coherence by synchronous bifocal transcranial
      magnetic stimulation.
AB  - Interregional coupling of distant brain regions can be measured by
      electroencephalographic (EEG) coherence reflecting the spatial-temporal
      correlation between two oscillatory signals. It has been suggested that this
      coherence in activity is a signature of functional integration of multimodal
      neuronal networks. Repetitive transcranial magnetic stimulation (rTMS) is a well
      established technique for non-invasive cortical stimulation. Its modulating
      effects outlast the train of stimulation and affect behavior. In the present
      study, we tested the hypothesis that cortico-cortical coherence between distant
      brain areas can be selectively enhanced by synchronous bifocal rTMS. Cortico
      cortical coherence was assessed in 16 healthy human subjects before and after
      three trains of synchronous high-frequency (10 Hz) rTMS to the left primary motor
      cortex and the visual cortex at the occipital pole simultaneously. Stimulation of
      the left M1 alone served as the control condition. Coherence and spectral power
      were measured between these areas on the stimulated and the homologue
      contralateral side. Synchronous bifocal rTMS induced an increase of interregional
      coupling in the alpha and lower beta band on the stimulated side without effects
      on spectral power. These data indicate that synchronous bifocal rTMS is a
      feasible technique for selective modulation of interregional EEG coherence.
      Furthermore, they raise the hypothesis that interventional enhancement of long
      range coherence may effectively modulate interregional integration with
      behavioral consequences.

PMID- 18336567
TI  - Developmental regulation of the morphology of mouse retinal horizontal cells by
      visual experience.
AB  - Visual deprivation during development alters the normal refinement of
      connections, neurotransmitter expression and physiological function in the
      retina. We investigated the effects of different forms of visual experience on
      the anatomy of retinal neurons in the mouse. Although it is generally assumed
      that outer retinal cells are not affected morphologically by visual experience,
      we found changes in the outer retinas of animals reared with light but no
      contrast. In postnatal day 30 animals reared in control, dark and high-contrast
      environments, horizontal-cell processes ramified normally in the outer plexiform
      layer. However, in postnatal day 30 no-contrast-reared retinas, horizontal-cell
      processes emerged from the outer plexiform layer and ramified in the inner
      nuclear layer. Similar sprouting processes of horizontal cells were found in a
      mouse model of retinitis pigmentosa. In conclusion, our data show that a lack of
      contrast during development alters the morphology of horizontal cells and may
      thus affect normal visual processing. This effect may be relevant for young
      patients with cloudy vision (e.g. cataract).

PMID- 18336568
TI  - Electroconvulsive seizure restores neurogenesis and hippocampus-dependent fear
      memory after disruption by irradiation.
AB  - Ongoing neurogenesis in the adult hippocampus is thought to play a role in
      learning and memory processes, and in response to antidepressant treatments. Low
      doses of irradiation (IRR) produce a significant long-lasting inhibitory effect
      on hippocampal neurogenesis that correlates with long-lasting behavioral
      deficits. Here we report that electroconvulsive seizure (ECS), which robustly
      increases adult neurogenesis in naive animals, also reverses the disruption of
      neurogenesis produced by IRR exposure. Moreover, we find that vascular
      endothelial growth factor (VEGF) is an essential mediator of this effect.
      Expression of VEGF in the granule cell layer (GCL) of the hippocampus is
      decreased by IRR, and ECS administration reverses this deficit in VEGF. There is
      a corresponding alteration in the number of endothelial cells, which express
      VEGF, in the hippocampal GCL following IRR and ECS. We also find that blockade of
      VEGF signaling attenuates ECS-induced proliferation, and VEGF infusion partially
      restores proliferation in irradiated animals. To examine the functional
      consequences of IRR and ECS on neurogenesis, hippocampus-dependent contextual
      fear conditioning was assessed. We found that following disruption by IRR, ECS
      restores contextual learning to baseline levels at time points consistent with
      its effects on neurogenesis. These findings demonstrate that ECS, in part via
      induction of VEGF, can reverse long-term neurogenesis deficits resulting from
      IRR, and that these effects have functional consequences on hippocampus-dependent
      fear memory.

PMID- 18336569
TI  - L-type calcium channels are involved in fast endocytosis at the mouse
      neuromuscular junction.
AB  - We used fluorescence microscopy of FM dyes-labeled synaptic vesicles and
      electrophysiological recordings to examine the functional characteristics of
      vesicle recycling and study how different types of voltage-dependent Ca(2+)
      channels (VDCCs) regulate the coupling of exocytosis and endocytosis at mouse
      neuromuscular junction. Our results demonstrate the presence of at least two
      different pools of recycling vesicles: a high-probability release pool (i.e. a
      fast destaining vesicle pool), which is preferentially loaded during the first 5
      s (250 action potentials) at 50 Hz; and a low-probability release pool (i.e. a
      slow destaining vesicle pool), which is loaded during prolonged stimulation and
      keeps on refilling after end of stimulation. Our results suggest that a fast
      recycling pool mediates neurotransmitter release when vesicle use is minimal
      (i.e. during brief high-frequency stimulation), while vesicle mobilization from a
      reserve pool is the prevailing mechanism when the level of synaptic activity
      increases. We observed that specific N- and L-type VDCC blockers had no effect on
      evoked transmitter release upon low-frequency stimulation (5 Hz). However, at
      high-frequency stimulation (50 Hz), L-type Ca(2+) channel blocker increased FM2
      10 destaining and at the same time diminished quantal release. Furthermore, when
      L-type channels were blocked, FM2-10 loading during stimulation was diminished,
      while the amount of endocytosis after stimulation was increased. Our experiments
      suggest that L-type VDCCs promote endocytosis of synaptic vesicles, directing the
      newly formed vesicles to a high-probability release pool where they compete
      against unused vesicles.

PMID- 18336570
TI  - Dissociation of the morphological correlates of stress-induced anxiety and fear.
AB  - Chronic stress is a powerful modulator of emotional behaviour. Previous studies
      have shown that distinct neuronal pathways modulate different emotional
      behaviours: while the amygdala plays a key role in fear-conditioned-to-cue
      stimuli, the bed nucleus of stria terminalis (BNST) is implicated in anxiety
      behaviour and responses to contextual stimuli. In addition, the BNST is directly
      involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. In
      the present study, we assessed anxiety (measured in the elevated-plus maze and
      acoustic startle apparatus) and fear-conditioned responses to light stimuli in
      rats that had been exposed to either chronic unpredictable stress or
      corticosterone for 28 days; thereafter, stereological estimates of the BNST and
      amygdaloid complex were performed, followed by three-dimensional morphometric
      dendritic analysis. Results show that chronic stress induces hyperanxiety without
      influencing fear conditioning or locomotion and exploratory activity. Stress
      induced hyperanxiety was correlated with increased volumes of the BNST but not of
      the amygdala. Dendritic remodelling was found to make a significant contribution
      to the stress-induced increase in BNST volume, primarily due to changes in the
      anteromedial area of the BNST, an area strongly implicated in emotional behaviour
      and in the neuroendocrine control of the stress response. Importantly, all of the
      effects of stress were recapitulated by exogenous corticosterone. In conclusion,
      this study shows that chronic stress impacts on BNST structure and function; its
      findings pertain to the modulation of emotional behaviour and the maladaptive
      response to stress.

PMID- 18336571
TI  - The neural dynamics of timed motor tasks: evidence from a synchronization
      continuation paradigm.
AB  - Distinct processing that integrates an accurate time scale is necessary for
      optimal motor behaviour. In the present study, corticocortical interactions as
      determined by EEG coherence were assessed in a synchronization-continuation
      paradigm during which subjects initially performed tapping movements in synchrony
      with external cues, followed by internal pacing of the target interval when the
      metronome was switched off. Unimanual and bimanual tasks were executed, and
      continuation of tapping was conducted with the same or different effector(s). The
      data showed an increased degree of mesial-central connectivity in the unpaced as
      compared to paced performance that was independent of task complexity, pointing
      to a general intensified demand of temporal processing when external cues are
      unavailable. When switching temporal information between effectors, coherence
      increased across the motor network. This increase depended upon preceding task
      complexity, and was most prominent for interhemispheric connections when
      performing unimanual tasks following bimanual pacing. Overall the data illustrate
      that timing of skilled actions can easily be transferred between effectors,
      although increased neural resources are required to conform to the temporal and
      motor constraints.

PMID- 18336572
TI  - Personality-dependent dissociation of absolute and relative loss processing in
      orbitofrontal cortex.
AB  - A negative outcome can have motivational and emotional consequences on its own
      (absolute loss) or in comparison to alternative, better, outcomes (relative
      loss). The consequences of incurring a loss are moderated by personality factors
      such as neuroticism and introversion. However, the neuronal basis of this
      moderation is unknown. Here we investigated the neuronal basis of loss processing
      and personality with functional magnetic resonance imaging in a choice task. We
      separated absolute and relative financial loss by sequentially revealing the
      chosen and unchosen outcomes. With increasing neuroticism, activity in the left
      lateral orbitofrontal cortex (OFC) preferentially reflected relative rather than
      absolute losses. Conversely, with increasing introversion, activity in the right
      lateral OFC preferentially reflected absolute rather than relative losses. These
      results suggest that personality affects loss-related processing through the
      lateral OFC, and propose a dissociation of personality dimension and loss type on
      the neuronal level.

PMID- 18336573
TI  - Calcium-independent phospholipase A2 mediates proliferation of human promonocytic
      U937 cells.
AB  - We have investigated the possible involvement of two intracellular phospholipases
      A(2), namely group VIA calcium-independent phospholipase A(2) (iPLA(2)-VIA) and
      group IVA cytosolic phospholipase A(2) (cPLA(2)alpha), in the regulation of human
      promonocytic U937 cell proliferation. Inhibition of iPLA(2)-VIA activity by
      either pharmacological inhibitors such as bromoenol lactone or methyl arachidonyl
      fluorophosphonate or using specific antisense technology strongly blunted U937
      cell proliferation. In contrast, inhibition of cPLA(2)alpha had no significant
      effect on U937 proliferation. Evaluation of iPLA(2)-VIA activity in cell cycle
      synchronized cells revealed highest activity at G(2)/M and late S phases, and
      lowest at G(1). Phosphatidylcholine levels showed the opposite trend, peaking at
      G(1) and lowest at G(2)/M and late S phase. Reduction of U937 cell proliferation
      by inhibition of iPLA(2)-VIA activity was associated with arrest in G(2)/M and S
      phases. The iPLA(2)-VIA effects were found to be independent of the generation of
      free arachidonic acid or one of its oxygenated metabolites, and may work through
      regulation of the cellular level of phosphatidylcholine, a structural lipid that
      is required for cell growth/membrane expansion.

PMID- 18336574
TI  - Engineering triterpene production in Saccharomyces cerevisiae-beta-amyrin
      synthase from Artemisia annua.
AB  - Using a degenerate primer designed from triterpene synthase sequences, we have
      isolated a new gene from the medicinal plant Artemisia annua. The predicted
      protein is highly similar to beta-amyrin synthases (EC 5.4.99.-), sharing amino
      acid sequence identities of up to 86%. Expression of the gene, designated AaBAS,
      in Saccharomyces cerevisiae, followed by GC/MS analysis, confirmed the encoded
      enzyme as a beta-amyrin synthase. Through engineering the sterol pathway in S.
      cerevisiae, we explore strategies for increasing triterpene production, using
      AaBAS as a test case. By manipulation of two key enzymes in the pathway, 3
      hydroxy-3-methylglutaryl-CoA reductase and lanosterol synthase, we have improved
      beta-amyrin production by 50%, achieving levels of 6 mg.L(-1) culture. As we have
      observed a 12-fold increase in squalene levels, it appears that this strain has
      the capacity for even higher beta-amyrin production. Options for further
      engineering efforts are explored.

PMID- 18336575
TI  - Identification of critical residues of subunit H in its interaction with subunit
      E of the A-ATP synthase from Methanocaldococcus jannaschii.
AB  - The boomerang-like H subunit of A(1)A(0) ATP synthase forms one of the peripheral
      stalks connecting the A(1) and A(0) sections. Structural analyses of the N
      terminal part (H1-47) of subunit H of the A(1)A(0) ATP synthase from
      Methanocaldococcus jannaschii have been performed by NMR spectroscopy. Our
      initial NMR structural calculations for H1-47 indicate that amino acid residues 7
      44 fold into a single alpha-helical structure. Using the purified N- (E1-100) and
      C-terminal domains (E101-206) of subunit E, NMR titration experiments revealed
      that the N-terminal residues Met1-6, Lys10, Glu11, Ala15, Val20 and Glu24 of H1
      47 interact specifically with the N-terminal domain E1-100 of subunit E. A more
      detailed picture regarding the residues of E1-100 involved in this association
      was obtained by titration studies using the N-terminal peptides E1-20, E21-40 and
      E41-60. These data indicate that the N-terminal tail E41-60 interacts with the N
      terminal amino acids of H1-47, and this has been confirmed by fluorescence
      correlation spectroscopy results. Analysis of (1)H-(15)N heteronuclear single
      quantum coherence (HSQC) spectra of the central stalk subunit F in the presence
      and absence of E101-206 show no obvious interaction between the C-terminal domain
      of E and subunit F. The data presented provide, for the first time, structural
      insights into the interaction of subunits E and H, and their arrangement within
      A(1)A(0) ATP synthase.

PMID- 18336576
TI  - ATPase activity of RecD is essential for growth of the Antarctic Pseudomonas
      syringae Lz4W at low temperature.
AB  - RecD is essential for growth at low temperature in the Antarctic psychrotrophic
      bacterium Pseudomonas syringae Lz4W. To examine the essential nature of its
      activity, we analyzed wild-type and mutant RecD proteins with substitutions of
      important residues in each of the seven conserved helicase motifs. The wild-type
      RecD displayed DNA-dependent ATPase and helicase activity in vitro, with the
      ability to unwind short DNA duplexes containing only 5' overhangs or forked ends.
      Five of the mutant proteins, K229Q (in motif I), D323N and E324Q (in motif II),
      Q354E (in motif III) and R660A (in motif VI) completely lost both ATPase and
      helicase activities. Three other mutants, T259A in motif Ia, R419A in motif IV
      and E633Q in motif V exhibited various degrees of reduction in ATPase activity,
      but had no helicase activity. While all RecD proteins had DNA-binding activity,
      the mutants of motifs IV and V displayed reduced binding, and the motif II mutant
      showed a higher degree of binding to ssDNA. Significantly, only RecD variants
      with in vitro ATPase activity could complement the cold-sensitive growth of a
      recD-inactivated strain of P. syringae at 4 degrees C. These results suggest that
      the requirement for RecD at lower temperatures lies in its ATP-hydrolyzing
      activity.

PMID- 18336577
TI  - Controlled, comparative study of relation between volume changes and interface
      pressure under short-stretch bandages in leg lymphedema patients.
AB  - BACKGROUND: Pressure loss under short-stretch bandages (SSBs) is a well-known
      phenomenon and is thought to be related to bandage relaxation and poor quality of
      application. AIM: The aim was to demonstrate that therapeutically intended volume
      reduction of the compressed leg is the most important cause for the loss of
      bandage pressure. DESIGN: This was an experimental, controlled comparative study.
      METHODS: In 20 patients suffering from lymphedema of the lower extremities and in
      9 healthy persons, lower leg volume was measured by water displacement. After
      application of a pressure measurement device (Kikuhime) at the B1 region, SSBs
      were applied on one leg according to a standard protocol. Volume and pressure
      measurements were performed at 0, 2, and 24 hours in supine as well as standing
      positions. RESULTS: A significant reduction of leg volume is already achieved 2
      hours after bandage application, both in lymphedema patients and in normal
      controls. A further volume decrease of the lymphedematous legs is observed in the
      following 24 hours after application of a new bandage (-290 mL). The volume
      reduction is associated with a significant loss of bandage pressure from initial
      values over 60 mmHg by 37 and 48% in controls and lymphedema patients,
      respectively. CONCLUSIONS: Inelastic, multilayer, multicomponent compression
      bandages lead to an immediate reduction of leg volume, both in lymphedematous and
      in normal legs. This therapeutically intended volume reduction seems to be the
      main reason for the fast decrease of the subbandage pressure. This study was
      supported by Lohmann & Rauscher, Ltd. Germany.

PMID- 18336578
TI  - Stretch marks: treatment using the 1,064-nm Nd:YAG laser.
AB  - BACKGROUND: Striae are frequent skin lesions that cause considerable aesthetic
      concern. The 1,064-nm long-pulsed Nd:YAG laser has been used to promote an
      increase in dermal collagen and is known to be a laser that has a high affinity
      for vascular chromophores. OBJECTIVE: This study aims to verify the efficacy of
      the long-pulsed Nd:YAG laser in the treatment of immature striae. MATERIALS AND
      METHODS: Twenty patients who had immature striae, i.e., red striae, were treated
      using the 1,064-nm long-pulsed Nd:YAG laser. The analysis of treatment efficacy
      was performed by the comparison between the images taken before and after each
      treatment session as well as through a subjective assessment carried out by the
      patients themselves. RESULTS: Results were considered satisfactory to both
      patients and doctors. A higher number of patients (55%) considered the results
      excellent when compared to the same assessment made by the doctor (40%).
      CONCLUSION: The clinical improvement of immature striae can be obtained with the
      use of the 1,064-nm long-pulsed Nd:YAG laser. The low incidence of side effects
      makes this laser a good alternative in the treatment of these common skin
      lesions.

PMID- 18336579
TI  - Neural activity-dependent regulation of gene expression in developing and mature
      neurons.
AB  - Neurons can change their gene expression patterns according to the inputs they
      have received. This activity-dependent gene regulation mechanism plays an
      important role in the formation of neural circuits during development. Further,
      by regulating the synaptic plasticity, this mechanism may function as an
      essential one for each organism to adapt flexibly to its environment. This review
      summarizes our current knowledge about the activity-dependent gene regulation
      mechanism in neurons, focusing on the transcription factors and signaling
      pathways involved in this mechanism.

PMID- 18336580
TI  - Neuronal stem/progenitor cells in the vertebrate eye.
AB  - We acquire information from the outside world through our eyes which contain the
      retina, the photosensitive component of the central nervous system. Once the
      adult mammalian retina is damaged, the retinal neuronal death causes a severe
      loss of visual function. It has been believed that the adult mammalian retina had
      no regenerative capacity. However, the identification of neuronal progenitor
      cells in the retina sheds some light on cellular therapies for damaged retinal
      regeneration. In this review, we highlight three potential stem/progenitor cells
      in the eye, the ciliary body epithelium cells, the iris pigmented epithelium
      cells, and Muller glia. In order to make them prime candidates for the possible
      treatment of retinal diseases, it is important to understand their basic
      characters. In addition, we discuss the key signaling molecules that function
      extracellularly and determine whether neuronal progenitors remain quiescent,
      proliferate, or differentiate. Finally, we introduce a secreted protein,
      Tsukushi, which is a possible candidate as a niche molecule for retinal
      stem/progenitor cells.

PMID- 18336581
TI  - Determinative roles of FGF and Wnt signals in iris-derived lens regeneration in
      newt eye.
AB  - Total regeneration of experimentally excised lens from the dorsal part of the
      iris-pigmented epithelium of newts has been a key model of tissue regeneration
      via cells originating from a foreign tissue. Due to the strict spatial
      restriction of the lens origin in the newt iris, it has often been assumed that
      only the dorsal iris cells are endowed with an intrinsic potential to give rise
      to lens tissues. However, our reinvestigation of the process revealed completely
      different mechanisms underlying lens regeneration and its spatial restriction,
      comprising the following two steps: (i) Fibroblast growth factor (FGF) 2
      dependent proliferation of iris-pigmented epithelium and activation of early lens
      genes (Pax6, Sox2, MafB) over the entire circumference of the iris; and (ii)
      dorsal iris-restricted activation of the canonical Wnt signals (involving Wnt2b
      and Frizzeld4) that leads to localized expression of late lens genes (Prox1,
      Sox1, beta-crystallin). Injection of FGF2 into normal eyes specifically elicited
      the second lens development from the dorsal iris, and the administration of
      recombinant Wnt3a to the cultured iris-pigmented epithelium caused even ventral
      iris-derived lens development. Thus, it is concluded that the regulation of FGF2
      and Wnt signals is a determinative of the iris-derived lens regeneration in the
      newt eye.

PMID- 18336582
TI  - Analysis of the expression and function of Wnt-5a and Wnt-5b in developing and
      regenerating axolotl (Ambystoma mexicanum) limbs.
AB  - Urodele amphibians are unique adult vertebrates because they are able to
      regenerate body parts after amputation. Studies of urodele limb regeneration, the
      key model system for vertebrate regeneration, have led to an understanding of the
      origin of blastema cells and the importance of positional interactions between
      blastema cells in the control of growth and pattern formation. Progress is now
      being made in the identification of the signaling pathways that regulate
      dedifferentiation, blastema morphogenesis, growth and pattern formation. Members
      of the Wnt family of secreted proteins are expressed in developing and
      regenerating limbs, and have the potential to control growth, pattern formation
      and differentiation. We have studied the expression of two non-canonical Wnt
      genes, Wnt-5a and Wnt-5b. We report that they are expressed in equivalent
      patterns during limb development and limb regeneration in the axolotl (Ambystoma
      mexicanum), and during limb development in other tetrapods, implying conservation
      of function. Our analysis of the effects of ectopic Wnt-5a expression is
      consistent with the hypothesis that canonical Wnt signaling functions during the
      early stages of regeneration to control the dedifferentiation of stump cells
      giving rise to the regeneration-competent cells of the blastema.

PMID- 18336583
TI  - Novel genes involved in canonical Wnt/beta-catenin signaling pathway in early
      Ciona intestinalis embryos.
AB  - We report here characterization of five genes for novel components of the
      canonical Wnt/beta-catenin signaling pathway. These genes were identified in the
      ascidian Ciona intestinalis through a loss-of-function screening for genes
      required for embryogenesis with morpholinos, and four of them have counterparts
      in vertebrates. The five genes we studied are as follows: Ci-PGAP1, a Ciona
      orthologue of human PGAP1, which encodes GPI (glycosylphosphatidylinositol)
      inositol-deacylase, Ci-ZF278, a gene encoding a C2H2 zinc-finger protein, Ci
      C10orf11, a Ciona orthologue of human C10orf11 that encodes a protein with
      leucine-rich repeats, Ci-Spatial/C4orf17, a single counterpart for two human
      genes Spatial and C4orf17, and Ci-FLJ10634, a Ciona orthologue of human FLJ10634
      that encodes a member of the J-protein family. Knockdown of each of the genes
      mimicked beta-catenin knockdown and resulted in suppression of the expression of
      beta-catenin downstream genes (Ci-FoxD, Ci-Lhx3, Ci-Otx and Ci-Fgf9/16/20) and
      subsequent endoderm formation. For every gene, defects in knockdown embryos were
      rescued by overexpression of a constitutively active form, but not wild-type, of
      Ci-beta-catenin. Dosage-sensitive interactions were found between Ci-beta-catenin
      and each of the genes. These results suggest that these five genes act upstream
      of or parallel to Ci-beta-catenin in the Wnt/beta-catenin signaling pathway in
      early Ciona embryos.

PMID- 18336584
TI  - The eye in focus: accommodation and presbyopia.
AB  - Current understanding of the anatomy, function and performance of the
      accommodative system of the young, adult human eye is outlined. Most major
      current models of the accommodative mechanism are based on Helmholtz's original
      ideas but, despite of a growing volume of related research, uncertainty continues
      over the relative contributions made to the overall mechanism by different ocular
      structures. The changes with age are then discussed. Although the amplitude of
      accommodation decreases steadily from later childhood, the speed and accuracy of
      the system within the available amplitude are little impaired until the age of
      about 40, when the amplitude falls below that needed for normal near work. A
      review of the available evidence on age-related change in the lens, capsule,
      ciliary body and other relevant ocular structures confirms that geometric and
      viscoelastic lenticular changes play major roles in the progressive loss of
      accommodation. Other factors may also contribute in an, as yet, unquantified way
      and a full understanding of the origins of presbyopic change remains elusive.

PMID- 18336585
TI  - Prognostic significance of foetal-like tyrosine kinase 3 mutation in Egyptian
      children with acute leukaemia.
AB  - The foetal like tyrosine kinase 3 mutation (Flt3) gene encodes a tyrosine kinase
      receptor that regulates proliferation and differentiation of haematopoietic stem
      cells. In children with acute myelogenous leukaemia (AML), internal tandem
      duplication of the Flt3 gene (Flt3/ITD) was previously reported and correlated to
      poor prognosis. Limited data are available about childhood acute lymphoblastic
      leukaemia (ALL). We analysed bone marrow specimens from 55 newly diagnosed acute
      leukaemia cases including 30 AML and 25 ALL by genomic PCR for the presence of
      Flt3/ITD and correlated its presence with clinical outcome. Tandem duplication
      was found in 6/30(20%) AML cases: 2/8 M1, 1/8 M2, 2/6 M3, 1/6 M4 with loss of
      heterozygosity (LOH) in two cases. Four of the cases with duplication were males
      and the other two cases were females. Complete remission was achieved in 16.6% of
      cases with duplication vs. 45.8% in cases without duplication. Failure to achieve
      induction remission was noted in 50% of cases with duplication vs. 29.1% in cases
      without duplication. FLt3/ITD was not found in ALL cases. Lineage restriction
      analysis revealed that Flt3/ITD was not present in lymphocytes, suggesting a lack
      of stem cell involvement for this mutation. Flt3/ITD was the most significant
      prognostic factor as declared by multivariate analysis. Patients with Flt3/ITD
      appear to be refractory to primary induction therapy, and for those who achieve
      remission, there is a high rate of relapse and death so there may be an
      association between this type of mutation and patient outcome.

PMID- 18336586
TI  - A novel locus for dHMN with pyramidal features maps to chromosome 4q34.3-q35.2.
AB  - The distal hereditary motor neuropathy (dHMN) is a rare genetically and
      clinically heterogeneous disorder characterized by weakness and wasting of distal
      limb muscles in absence of overt sensory abnormalities. Recently, pyramidal signs
      have been also described in some patients with dominant or recessive dHMN, and
      two different loci have been identified in families affected by dHMN complicated
      with pyramidal dysfunction. We investigated an Italian family affected by an
      autosomal dominant dHMN complicated by pyramidal signs in order to map a new gene
      locus. The disease maps to a novel locus in a 26-cM region flanked by D4S1552 and
      D4S2930 on chromosome 4q34.3-35.2. Three candidate genes (SNX25, CASP3 and
      TUBB4Q) located in the critical region were screened for the presence of
      mutations by heteroduplex analysis. No mutations have been detected in the
      analyzed genes. In conclusion, the new private genetic locus we reported further
      confirms the wide heterogeneity of dHMN.

PMID- 18336587
TI  - A re-examination of the chromosome 8p22-8p23.1 region in Kabuki syndrome.

PMID- 18336588
TI  - Intrahepatic endothelial and Kupffer cells involved in immunosuppressive
      cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis.
AB  - During acute viral hepatitis, the intrahepatic tolerance sustained by
      immunosuppressive cytokines such as interleukin (IL)-4, IL-10, transforming
      growth factor (TGF)-beta and prostaglandin E2 (PGE2), produced by Kupffer cells
      (KC), liver sinusoidal endothelial cells (LSEC), natural killer (NK) T cells and
      natural regulatory T cells may be disturbed. NK cells are recruited normally in
      the liver and produce interferon (IFN)-gamma to control viral replication. The
      use of mouse hepatitis virus type 3 (MHV3) attenuated variants showing selected
      tropisms for KC or LSEC have allowed determining their roles in the disturbances
      of immune tolerance during viral hepatitis. Groups of C57BL/6 mice were infected
      with the pathogenic L2-MHV3 (KC+, LSEC+), low attenuated 51.6-MHV3 (KC+, LSEC-)
      or high attenuated CL12-MHV3 (KC-, LSEC-) variants for the first 3 days. Results
      showed that IL-10, TGF-beta and PGE2 production in the liver decreased in L2-MHV3
      infected mice and increased in 51.6-MHV3- and CL12-MHV3-infected mice. The ratio
      of IFN-gamma/IL-4 in liver decreased in L2-MHV3-infected mice, while it was not
      (or low) altered in mice infected with the attenuated MHV3 variant mice.
      Phenotypic analysis of intrahepatic mononuclear cells revealed that apoptotic NK
      and NK T cells increased in mice infected with the L2-MHV3, but were minor in
      51.6-MHV3- and CL12-MHV3-infected mice. The numbers of CD4+ forkhead box P3+
      cells increased in the livers from low pathogenic CL12-MHV3 and YAC-MHV3-infected
      mice. These results indicate that viral permissivity of KC and LSEC is involved
      in the decrease of IL-10 and PGE2, while KC may play an additional role in the
      apoptosis of NK and NK T cells during acute viral hepatitis.

PMID- 18336589
TI  - Involvement of innate immunity in the pathogenesis of intestinal Behcet's
      disease.
AB  - The involvement of excessive T helper 1 (Th1) cell functions in the pathogenesis
      of Behcet's disease (BD) has been reported. We therefore studied Toll-like
      receptor (TLR)-expressing cells, which play important roles in innate immunity in
      patients with BD. Peripheral blood mononuclear cells (PBMC) of BD and healthy
      controls, and tissue specimens of intestinal BD and Crohn's disease (CD) were
      analysed for messenger RNA (mRNA) and protein expressions by reverse
      transcription-polymerase chain reaction and immunostaining respectively. PBMC of
      BD expressed TLR-2 and TLR-4 mRNA almost comparable with healthy controls.
      Intestinal lesions of BD expressed TLR-2 and TLR-4 mRNA consistently. In
      contrast, TLR-4 mRNA was expressed preferentially and TLR-2 mRNA was expressed
      less frequently in CD lesions. In intestinal samples of BD, TLR-2 and TLR-4 mRNA
      were detected in ileocaecal ulcer lesions, but not in unaffected sites of the
      same sample, indicating the association of the TLR expression with the disease
      manifestation of intestinal BD. TLR-2-expressing cells which were simultaneously
      cluster of distribution (CD)68-positive produced interleukin (IL)-12 in the
      lesions, indicating the participation of TLR-2-expressing cells in the Th1 skewed
      responses in vivo. As a possible ligand of TLR-2, in BD self-heat shock protein
      60 was expressed in peripheral blood lymphocytes and intestinal tissues.
      Collectively, TLR-2-expressing cells as well as TLR-4-expressing cells
      accumulated in the intestinal lesions of BD. IL-12 produced by TLR-2-expressing
      cells may contribute to the induction of Th1-dominant immune responses in
      intestinal BD.

PMID- 18336590
TI  - Innate lymphocyte and dendritic cell cross-talk: a key factor in the regulation
      of the immune response.
AB  - Dendritic cells (DC) are specialized in the presentation of antigens and the
      initiation of specific immune responses. They have been involved recently in
      supporting innate immunity by interacting with various innate lymphocytes, such
      as natural killer (NK), NK T or T cell receptor (TCR)-gammadelta cells. The
      functional links between innate lymphocytes and DC have been investigated widely
      and different studies demonstrated that reciprocal activations follow on from
      NK/DC interactions. The cross-talk between innate cells and DC which leads to
      innate lymphocyte activation and DC maturation was found to be multi-directional,
      involving not only cell-cell contacts but also soluble factors. The final outcome
      of these cellular interactions may have a dramatic impact on the quality and
      strength of the down-stream immune responses, mainly in the context of early
      responses to tumour cells and infectious agents. Interestingly, DC, NK and TCR
      gammadelta cells also share similar functions, such as antigen uptake and
      presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and
      NK T cells have the ability to kill DC. This review will focus upon the different
      aspects of the cross-talk between DC and innate lymphocytes and its key role in
      all the steps of the immune response. These cellular interactions may be
      particularly critical in situations where immune surveillance requires efficient
      early innate responses.

PMID- 18336591
TI  - Inhibition of casein kinase 2 enhances the death ligand- and natural kiler cell
      induced hepatocellular carcinoma cell death.
AB  - Recent studies have shown that the inhibition of casein kinase 2 (CK2) sensitizes
      many cancer cells to Fas ligand- and tumour necrosis factor-related apoptosis
      inducing ligand (TRAIL)-induced apoptosis. However, it has not been demonstrated
      directly whether CK2 inhibition can also enhance the cytotoxicity of natural
      killer (NK) cells, which actually use the death ligands to kill cancer cells in
      vivo. To address whether NK cell-mediated cancer cell death is affected by the
      inhibition of CK2, we first checked whether the death ligand-induced apoptosis of
      hepatocellular carcinoma cells (HCCs) and HeLa were affected by CK2 inhibition.
      We then investigated the effect of CK2 inhibition on NK cytotoxicity against HCCs
      and HeLa cells and its mechanistic features. Inhibition of CK2 by emodin
      increased the apoptotic cell death of HepG2, Hep3B and HeLa when the cancer cell
      lines were treated with a soluble form of recombinant TRAIL or an agonistic
      antibody of Fas. This phenomenon appeared to be correlated with the expression
      level of death receptors on the cancer cell surface. More interestingly, the
      inhibition of CK2 also greatly increased the NK cell-mediated cancer cell
      killing. The NK cytotoxicity against the cancer cells increased about twofold
      when the target cells were pretreated with a specific CK2 inhibitor, emodin or
      4,5,6,7-tetrabromobenzotriazole. Furthermore, the increase of the NK cytotoxicity
      against cancer cells by CK2 inhibition was granule-independent and mediated
      possibly by the death ligands on the NK cell surface. This suggests that CK2
      inhibitors could be used to enhance the cytotoxicity of NK cells and consequently
      increase host tumour immunity.

PMID- 18336592
TI  - CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13),
      ameliorates allergic airway inflammation.
AB  - Airway inflammation is characterized by selective recruitment of mononuclear and
      granulocytic cells. This recruitment is mediated by the action of chemotactic
      cytokines, such as chemokines. A number of chemokines and their receptors have
      been identified and proposed as potential therapeutic agents in allergic airway
      inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13),
      a CC chemokine that has been associated with allergic inflammatory diseases such
      as asthma and allergic rhinitis. To investigate alternative therapeutic agents to
      alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic
      peptides were designed and tested for their ability to modulate in vitro and in
      vivo chemokine-mediated functions. Our results show that one of these peptides,
      CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using
      monocytic cell lines. In addition, we found that CDIP-2 significantly reduced
      peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin
      induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered
      as part of a novel group of anti-inflammatory agents based on chemokine-derived
      synthetic peptides.

PMID- 18336593
TI  - Regulation of galectin-3 function in mucosal fibroblasts: potential role in
      mucosal inflammation.
AB  - Recently we identified galectin-3 (gal-3), which is secreted by colonic
      epithelial cells (CEC), to be a strong activator of colonic lamina propria
      fibroblasts (CLPF). Modulation of CLPF function may play a role during stricture
      and fistula formation in inflammatory bowel disease (IBD). Therefore, we
      investigated further the expression of gal-3 and effects on CLPF. The aim of this
      study is to perform a direct comparison of gal-3 between tissue from healthy
      controls and from patients with either Crohn's disease (CD) or ulcerative colitis
      (UC). CEC, CLPF and intestinal macrophages (IMAC) were isolated from control and
      IBD colonic tissue. Interleukin-8 secretion as a readout of CLPF activation was
      quantified by enzyme-linked immunosorbent assay. Gal-3 in cell cultures and
      tissue samples was evaluated by Western blot, immunofluorescence and
      immunohistochemistry. CLPF-migration was assayed in the 48-well modified Boyden
      chamber. Gal-3 expression was found in all segments of the colon. In the terminal
      ileum, less gal-3 was found compared with the colon. Immunohistochemistry and
      immunofluorescence revealed a homogenous distribution of gal-3 in CEC and IMAC of
      control mucosa and UC. However, significantly less gal-3 was found in IMAC from
      CD patients. In CD fistulae and stenoses, gal-3 expression was reduced
      significantly and barely detectable. In co-incubation studies lactose reduced
      significantly the CLPF-stimulatory potential of gal-3, indicating that the C
      terminal domain of gal-3 is responsible for CLPF activation. Gal-3 stimulated
      CLPF migration in CLPF derived from fistulae. In conclusion, gal-3 expression is
      down-regulated in CD-fistulae and stenoses as well as in IMAC in CD patients. Gal
      3 induces migration of CLPF derived from fistulae. Its role for stricture and
      fistula formation warrants further investigation.

PMID- 18336594
TI  - Secretory immunoglobulin A (IgA) responses in IgA nephropathy patients after
      mucosal immunization, as part of a polymeric IgA response.
AB  - Secretory immunoglobulin A (SIgA), although generated at mucosal surfaces, is
      also found in low concentrations in the circulation. Recently, SIgA was
      demonstrated in mesangial deposits of patients with immunoglobulin A nephropathy
      (IgAN), suggesting a role in the pathogenesis. This finding is in line with the
      belief that high molecular weight (HMW) immunoglobulin A (IgA) is deposited in
      the kidney. However, there is little information on the size distribution of
      antigen-specific IgA in circulation upon mucosal challenge. In this study we
      measured antigen-specific IgA, including SIgA, in serum following challenge of
      IgAN patients and controls via intranasal vaccination with a neoantigen, cholera
      toxin subunit B (CTB). We size-fractionated serum and nasal washes to study the
      size distribution of total IgA, SIgA and CTB-specific IgA. Finally, we compared
      the size distribution of antigen-specific IgA after mucosal immunization with the
      distribution upon systemic immunization. A significant induction of antigen
      specific SIgA was detectable in serum of both patients with IgAN and controls
      after mucosal immunization with CTB. Independent of the route of immunization, in
      both groups the antigen-specific IgA response was predominantly in the polymeric
      IgA fractions. This is in contrast to total IgA levels in serum that are
      predominantly monomeric. We conclude that mucosal challenge results in antigen
      specific SIgA in the circulation, and that the antigen-specific IgA response in
      both IgAN patients and in controls is of predominantly HMW in nature. No
      differences between IgAN patients and controls were detected, suggesting that the
      size distribution of antigen-specific IgA in the circulation is not disturbed
      specifically in IgAN patients.

PMID- 18336595
TI  - Mannan-binding lectin MBL2 gene polymorphism in chronic hepatitis C: association
      with the severity of liver fibrosis and response to interferon therapy.
AB  - Hepatitis C virus (HCV) is a major cause of hepatic disease and of liver
      transplantation worldwide. Mannan-binding lectin (MBL), encoded by the MBL2 gene,
      can have an important role as an opsonin and complement activating molecule in
      HCV persistence and liver injury. We assessed the MBL2 polymorphism in 102 Euro
      Brazilian patients with moderate and severe chronic hepatitis C, paired for
      gender and age with 102 HCV seronegative healthy individuals. Six common single
      nucleotide polymorphisms in the MBL2 gene, three in the promoter (H/L, X/Y and
      P/Q) and three in exon 1 (A, the wild-type, and B, C or D also known as O) were
      evaluated using real-time polymerase chain reaction with fluorescent
      hybridization probes. The concentration of MBL in plasma was measured by enzyme
      linked immunosorbent assay. The frequency of the YA/YO genotype was significantly
      higher in the HCV patients compared with the controls (P = 0.022). On the other
      hand, the genotypes associated with low levels of MBL (XA/XA, XA/YO and YO/YO)
      were decreased significantly in the patients with severe fibrosis (stage F4),
      when compared with the patients with moderate fibrosis (stage F2) (P = 0.04) and
      to the control group (P = 0.011). Furthermore, MBL2 genotypes containing X or O
      mutations were found to be associated with non-responsiveness to pginterferon and
      ribavirin treatment (P = 0.023). MBL2 polymorphisms may therefore be associated
      not only with the development of chronic hepatitis C, but also with its clinical
      evolution and response to treatment.

PMID- 18336596
TI  - Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes
      docetaxel-refractory prostate cancer PC-3 cells to chemotherapy.
AB  - OBJECTIVES: To characterize changes in secretory clusterin (sCLU) expression in
      prostate cancer cells after treatment with docetaxel and to determine whether
      sCLU knockdown can re-introduce chemosensitivity in a docetaxel-resistant,
      androgen-independent human prostate cancer model. PATIENTS AND METHODS: A tissue
      microarray was constructed for 84 radical prostatectomy (RP) specimens from a
      multicentre Phase II trial of neoadjuvant combined androgen ablation and
      docetaxel (CUOG-P01a) and assessed for changes in the expression of the
      cytoprotective chaperone sCLU. The human prostate cancer cell line PC-3 was
      repeatedly exposed to docetaxel chemotherapy in vitro, and a docetaxel-resistant
      cell subline (PC-3dR) was developed and analysed. RESULTS: sCLU levels were
      significantly higher in RP specimens treated with neoadjuvant combined androgen
      ablation and docetaxel than in untreated specimens. Similarly, sCLU expression
      increased 2.5-fold in the newly developed docetaxel-refractory PC-3dR cell line
      compared with parental PC-3 cells. There was a dose-dependent and sequence
      specific decrease in sCLU levels in PC-3dR cells using OGX-011, an antisense
      oligonucleotide against human sCLU. OGX-011 and small-interference RNA both
      chemosensitized PC-3dR cells to docetaxel and mitoxantrone in vitro and apoptotic
      rates in PC-3dR cells were significantly increased when OGX-011 was combined with
      docetaxel. In vivo, growth of PC-3dR xenografts in nude mice was synergistically
      inhibited by OGX-011 combined with paclitaxel or mitoxantrone (by 76% and 44%
      compared with their mismatch controls, respectively). CONCLUSION: The present
      findings indicate that targeted knockdown of sCLU enhances the effects of
      cytotoxic chemotherapy in docetaxel-refractory cells, and provide preclinical
      proof of principle for clinical trials testing OGX-011 in second-line
      chemotherapy regimens for patients with docetaxel-refractory prostate cancer.

PMID- 18336597
TI  - Hypermethylation of the thrombospondin-1 gene is associated with poor prognosis
      in penile squamous cell carcinoma.
AB  - OBJECTIVE: To evaluate the presence of human papillomavirus (HPV) infection, the
      methylation status in the promoter region of thrombospondin-1 (TSP-1), RAS
      association domain family 1A (RASSF1-A) and p16 genes, and the expression of TSP
      1, CD31, p16 and p53 proteins in patients diagnosed with penile cancer, and the
      possible associations between these variables and clinical and pathological
      features. PATIENTS AND METHODS: HPV types, gene promoter hypermethylation and
      protein expression were analysed by reverse line blot, methylation-specific
      polymerase chain reaction, and immunohistochemistry, respectively, in 24 penile
      squamous cell carcinomas. RESULTS: HPV infection was detected in 11 of 24 cases
      (46%), and TSP-1, RASSF1-A and p16 genes were hypermethylated in 46%, 42% and 38%
      of the tumours, respectively. TSP-1 hypermethylation was associated with
      unfavourable histological grade (grade 3; P = 0.033), vascular invasion (P =
      0.023), weak expression of TSP-1 protein (P = 0.041), and shorter overall
      survival (P = 0.04). TSP-1 expression was not associated with microvessel
      density. However, RASSF1-A hypermethylation was more frequent in T1 tumours (P =
      0.01), and p16 hypermethylation was not associated with any of the tested
      variables except for absence of p16 expression (P = 0.022). CONCLUSION: In
      summary, the epigenetic inactivation of TSP-1 and RASSF1-A genes is associated
      with pathological variables and seems to be of prognostic significance in penile
      cancer.

PMID- 18336598
TI  - Microsatellite analysis of allelic imbalance in tumour and blood from patients
      with prostate cancer.
AB  - OBJECTIVE: To investigate whether a high frequency of allelic imbalance (AI) is
      associated with clinicopathological variables of patients with prostate cancer.
      PATIENTS AND METHODS: We analysed loss of heterozygosity (LOH) and microsatellite
      (MS) instability (MSI) on circulating plasma DNA in a polymerase chain reaction
      (PCR)-based MS study of 230 patients with prostate cancer and 43 with benign
      prostatic hyperplasia (BPH) using a panel of 13 polymorphic MS markers. RESULTS:
      The overall incidence of AI was significantly higher in primary tumours (34%)
      than in blood plasma samples from patients with prostate cancer (11%). Although
      LOH (2.0%) and MSI (1.5%) were also found in BPH plasma samples, their
      frequencies were low. AI identified in plasma samples from patients with prostate
      cancer could be retrieved in 63% of the paired tumour samples. The highest
      concordance of AI and retention of heterozygosity between tumour and plasma
      samples was 83% at the marker D8S360. There were high frequencies of LOH at the
      markers THRB, D7S522 and D8S137 in both types of specimens. The markers D11S898
      and D11S1313 on the chromosome arm 11q showed frequent MSI. The comparison with
      established risk factors showed significant associations of an increase in
      prostate volume with AI at the combined markers D6S474/D7S522 in tumour tissues
      and at D7S522 in plasma samples (P < 0.04). In the primary tumours there was a
      further correlation of LOH at D11S1313 with increasing tPSA value (P = 0.005).
      The combination of total prostate-specific antigen (PSA) and % free PSA was
      associated with LOH at THRB in plasma samples. CONCLUSIONS: Plasma-based MS
      analysis may have clinical value for the molecular staging of prostate cancer.

PMID- 18336599
TI  - Scintigraphic renal function after unilateral pyeloplasty in children: a
      systematic review.
AB  - OBJECTIVE: To systematically review previous reports and thus determine the
      functional outcome after pyeloplasty in children with unilateral hydronephrosis
      due to pelvi-ureteric junction obstruction, and the possible variables that could
      affect it. METHODS: We searched Medline/PubMed, Embase, and Web of Science for
      articles in English published from 1966 to 2007, using both 'medical subject
      headings' and 'free text' protocols. Abstracts, full texts, and bibliographies of
      pertinent papers were reviewed to select studies of scintigraphic renal function
      before and after pyeloplasty. The postoperative change in scintigraphic renal
      function was assessed in relation to presentation (antenatal vs postnatal),
      timing of surgery (early vs delayed), age at surgery, and preoperative
      ultrasonography (US) and scintigraphic findings. RESULTS: Thirty-six studies
      (2.1% of the initial search) were eventually selected for review. Studies were
      generally of poor scientific quality and very heterogeneous in their indications
      for surgery and follow-up protocols. Postoperative function showed a wide
      variability. Symptomatic patients diagnosed postnatally seemed to have a greater
      chance of functional improvement after surgery than asymptomatic patients
      diagnosed antenatally. The chance of improvement seemed also to be greater in
      patients with moderately rather than severely impaired preoperative function.
      Otherwise, the improvement seemed unrelated to the age at surgery, the
      preoperative US findings, or the excretion pattern on renal scintigraphy. Of
      patients having delayed surgery >97.5% had preserved function afterward.
      CONCLUSIONS; Patients with moderately impaired preoperative function and those
      diagnosed postnatally because of symptoms are those with the greatest likelihood
      of having a functional improvement after surgery.

PMID- 18336600
TI  - Robotic and laparoscopic partial nephrectomy: a matched-pair comparison from a
      high-volume centre.
AB  - OBJECTIVES: To evaluate the relative merits of robotically assisted partial
      nephrectomy (RPN), using a matched-pair analysis, with laparoscopic PN (LPN).
      PATIENTS AND METHODS: Between July 2006 and August 2007, 12 patients had RPN for
      tumour; the outcomes were compared retrospectively with 12 matched patients who
      had LPN. Patients were matched for age, gender, body mass index, American Society
      of Anesthesiologists score, tumour side, size and location, and the specific
      technique used (early vs conventional unclamping). Operative measures evaluated
      included operative time, estimated blood loss, warm ischaemia time (WIT), and
      number of ports used. Outcomes measured included serum creatinine and estimated
      glomerular filtration rate before and after surgery, length of hospital stay,
      transfusion rate, operative and 30-day complication rate, and surgical margin
      status. RESULTS: Overall there were no differences in perioperative variables
      (WIT, estimated blood loss, surgery time, length of stay) between the groups.
      Fewer ports were used during LPN. Renal functional outcomes, transfusion rate and
      complication rates were comparable. Two RPN cases required conversion to standard
      LPN. A subset analysis of six patients in each group who had early unclamping
      showed a 7-min shorter WIT with LPN (14 vs 21 min, P = 0.05), despite larger
      tumours being treated with LPN (3 vs 2.4 cm, P < 0.01) in this subset.
      CONCLUSIONS: RPN is a developing procedure, and is technically feasible and safe,
      albeit with a longer warm WIT than LPN. Further experience is necessary to
      determine the relative merits of RPN.

PMID- 18336601
TI  - Penile and scrotal Paget's disease: 130 Chinese patients with long-term follow
      up.
AB  - OBJECTIVES: To report a retrospective series of 130 Chinese patients with
      penoscrotal extramammary Paget's diseases (EMPD), with a long-term follow-up, and
      thus improve the diagnosis and therapy of this disease. PATIENTS AND METHODS: The
      history, clinical presentation, pathology, treatment, and prognosis of 130
      patients were analysed. All cases were confirmed by skin biopsy, and then the
      patients had local wide resection to remove the involved skin and subcutaneous
      tissue. The large defective wound was reconstructed using a split-thickness skin
      graft or local flap. RESULTS: Forty-five patients were evaluated by frozen
      section biopsy of the margins during surgery, five of whom had positive margins
      and then had an extended resection immediately. Most of these patients had local
      skin or adjacent scrotal flaps to cover their skin defects. Of the 130 patients,
      81 had a mean (range) follow-up of 3.2 (0.5-10) years after surgery. Five of nine
      patients with positive margins and three (4%) of 72 with negative margins had
      tumour recurrence. Five patients died from metastatic disease. CONCLUSIONS:
      Penoscrotal EMPD needs be differentiated from other chronic dermatitis. A 3 cm
      surgical margin should be sufficient and frozen-section pathological examinations
      are necessary for some complicated conditions. Skin grafts or local flaps are
      good for large skin defects.

PMID- 18336602
TI  - Understanding the elements of overactive bladder: questions raised by the EPIC
      study.
AB  - OBJECTIVES: To compare the prevalence of frequency and nocturia and the bother
      they impose in a population-based sample of men and women using current
      International Continence Society (ICS) definitions of lower urinary tract
      symptoms (LUTS) and commonly used alternative definitions of these LUTS to
      emphasize the importance of standardizing the definitions when evaluating
      overactive bladder (OAB) syndrome; we also describe the spectrum of LUTS and
      bother they impose in this population with OAB. SUBJECTS AND METHODS: Several
      validated disease-specific measures were used in a population-based, cross
      sectional telephone survey of adults aged >or=18 years in five countries. The
      population with OAB was defined as those participants who answered 'yes' to
      questions about urgency or urgency urinary incontinence according to ICS
      standards. The prevalence of daytime frequency and nocturia within the OAB
      population was examined using two different criteria for each symptom. Frequency
      was defined using the current ICS definition (i.e. subject's perception of
      whether they urinated too often during the day) or more than eight daytime voids.
      Nocturia was defined according to the ICS definition of having to wake once or
      more per night to void and using the threshold of waking twice or more per night
      to urinate. Urinary symptom bother within the OAB population was compared using
      the different criteria for frequency and nocturia. RESULTS: In all, 1434
      participants (502 men and 932 women) were classified as having OAB; 31% of men
      and 25% of women with OAB had daytime frequency consistent with the ICS
      definition. The ICS-defined frequency identified a population with a varied
      distribution of reported daytime voiding frequencies; most respondents reported
      frequencies below the threshold of nine daytime voids. The ICS-defined daytime
      frequency was reported as bothersome by more than half of the OAB population (46%
      of men, 66% of women). Of the OAB population, approximately 75% reported one or
      more nocturia episodes per night, and approximately 40% reported two or more per
      night. The proportion of the OAB population that was bothered by nocturia
      increased markedly as the number of nocturia episodes increased. Among those with
      OAB, the most prevalent combination of OAB symptoms was urgency and nocturia.
      More than half of those with OAB reported urgency combined with three or more
      other LUTS (including voiding and postmicturition symptoms), and the number of
      LUTS reported increased with age. The proportion of the population reporting
      symptom bother increased as the number of reported LUTS in that population
      increased. CONCLUSIONS: The ICS definitions for daytime frequency as 'the
      subject's perception of urinating too often' and for nocturia as 'one or more
      episodes per night' adequately described bladder symptoms within the OAB
      population when assessed by the level of symptom bother. Urgency was uncommon in
      isolation and did not alone impose as high a level of bother as when combined
      with other LUTS. In this population, the most predominant manifestation of OAB
      was a combination of urgency with one or more other OAB symptoms. Symptom bother
      became more common as the number of symptoms reported increased. LUTS other than
      the defining symptoms of OAB were also highly prevalent within the OAB
      population.

PMID- 18336603
TI  - Components of the plasminogen activator system and their complexes in renal cell
      and bladder cancer: comparison between normal and matched cancerous tissues.
AB  - OBJECTIVE: To analyse and compare the concentration of plasminogen activator
      (PA), urokinase-type PA (uPA), tissue-type PA (tPA), PA inhibitor (PAI)-1 and PAI
      2, and the complexes uPA-PAI-1 and tPA-PAI-1 and calculated uPA and tPA
      uncomplexed with PAI-1 ('free') in urothelial cell carcinoma and matched benign
      urothelium, and in renal cell carcinoma (RCC) and matched benign renal tissue.
      PATIENTS AND METHODS: Tissue samples were obtained during cystectomy (33
      patients) and nephrectomy (55), and specific enzyme-linked immunosorbent assays
      were used to assess the PA components in extracts of these tissues. RESULTS:
      Tissue levels of uPA-PAI-1 and tPA-PAI-1, but also PAI-1 itself, were greater in
      tumorous bladder and kidney tissue than in matched normal tissue (by 1.5-7.8
      times). Free tPA was clearly lower in tumour tissue (by 0-0.12-fold). In bladder
      cancer, but not in RCC, levels of uPA (15.8-fold) and free uPA (16.4-fold) were
      greater in tumour tissue. Free uPA levels were less in RCC (0.41-fold). For both
      normal bladder and kidney tissue, there was no clear correlation between uPA-PAI
      1 complex and either component. However, the formation of tPA-PAI-1 complexes in
      normal bladder and kidney tissue was primarily determined by PAI-1.
      Interestingly, in tumour tissues there was a strong, significant correlation
      between complex levels and both components. CONCLUSION: RCC and bladder cancer
      show distinct profiles of components of the PA system. This study provides a
      basis for further studies into both the (patho)physiological role of the PA
      system in these tumours, and into a possible relation with tumour progression and
      prognosis, and as target for therapy.

PMID- 18336604
TI  - Antibiotics for transrectal ultrasonography-guided prostate biopsy: are we
      practising evidence-based medicine?

PMID- 18336605
TI  - Infections after prostate biopsy and antibiotic resistance.

PMID- 18336606
TI  - Changes in muscle, fat and bone mass after 36 weeks of maximal androgen blockade
      for prostate cancer.
AB  - OBJECTIVE: To assess the effects of androgen deprivation therapy (ADT) on whole
      body and regional muscle, fat and bone mass in men with prostate cancer without
      metastatic bone disease. PATIENTS AND METHODS: Seventy-two men aged 44-88 years
      underwent spine, hip and whole-body dual-energy X-ray absorptiometry scans at
      baseline and after 36 weeks of ADT. The change in whole-body and regional lean
      mass (LM), fat mass (FM), and bone mineral content and density (BMD) were
      determined. In addition, the prostate specific antigen (PSA), serum testosterone
      and haemoglobin levels were measured, and the level of physical activity and
      fatigue assessed using the European Organisation for Research and Treatment of
      Cancer Quality of Life Questionnaire-30. RESULTS: The upper limb, lower limb,
      trunk and whole-body LM decreased by a mean (sem) of 5.6 (0.6)%, 3.7 (0.5)%, 1.4
      (0.5)% and 2.4 (0.4)% (P < 0.01), respectively, while FM increased by 20.7
      (3.3)%, 18.7 (2.7)%, 12.0 (2.5)% and 13.8 (2.3)% (P < 0.001). Hip, spine, whole
      body and upper limb BMD decreased by 1.9 [corrected] (0.3)% [corrected], 3.3
      [corrected] (0.4)%, 1.6 [corrected] (0.3)% and 1.3 (0.3%) (P < 0.001), but not
      lower limb BMD. Serum testosterone, PSA and haemoglobin levels decreased by 93.3
      (0.4)%, 98.2 (0.5)%, and 8.8 (0.9)% (P < 0.001), respectively. In addition,
      physical activity levels decreased and levels of fatigue increased. CONCLUSION:
      After 36 weeks of ADT there was a significant decrease in whole-body and regional
      LM and bone mass, while whole-body and regional FM increased in older men with
      prostate cancer. Strategies to counteract changes in soft tissue and bone mass
      during ADT should be formulated to minimize the risk of sarcopenia, osteoporosis
      and obesity.

PMID- 18336607
TI  - Renal cell carcinoma metastatic to the stomach: single-centre experience and
      literature review.
AB  - OBJECTIVES: To investigate the incidence, clinical presentation and therapy of
      gastric metastases, an uncommon finding, in a large group of patients with renal
      cell carcinoma (RCC). PATIENTS AND METHODS: We systematically searched the
      computerized RCC database of our institute, covering 2082 patients (1180 men and
      902 women) who had surgery between January 1984 and September 2005, to identify
      those with a synchronous and/or metachronous diagnosis of cancer in gastric
      biopsies or resection specimens. The histopathological slides of both renal and
      gastric cancer probes, and the clinical presentation, treatment and outcome of
      affected patients, were reassessed. RESULTS: Twelve patients with primary gastric
      cancer, one with local RCC recurrence affecting the antrum and five with clear
      cell RCC (three men and two women; mean age 73 years, range 65-83) with
      haematogenous cancer spread to the stomach were detected. The mean (range) time
      to gastric metastasis was 6.9 (1.7-13.1) years. There were metastases to other
      organs, most often the lung, in all patients. Three patients presented with
      symptoms of gastrointestinal bleeding, which was successfully controlled by local
      endoscopic therapy. Four patients died from disease at 3-19 months after
      diagnosis. One patient is still alive with disease after approximately 2 years.
      CONCLUSIONS: Gastric metastasis in patients with RCC appears to be a late event
      in the course of the disease. Most patients show concomitant tumour spread to
      other organs, and the outcome is generally poor. The use of targeted drugs might
      offer a new perspective for affected patients.

PMID- 18336608
TI  - The prognostic role of the pathological T2 subclassification for prostate cancer
      in the 2002 Tumour-Nodes-Metastasis staging system.
AB  - OBJECTIVE: To evaluate the prognostic role of the 2002 Tumour-Nodes-Metastasis
      (TNM) pT2 subclassification for biochemical recurrence (BCR) after radical
      prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: The 1997 TNM
      staging system is based on one subdivision for organ-confined prostate tumours
      (T2a, unilateral; T2b, bilateral involvement). The 2002 TNM staging system
      subdivides unilateral involvement into T2a (half of one lobe or less) and T2b
      (more than one half of one lobe), while bilateral involvement is classified as
      T2c. In all, 542 patients were treated with RP at our institute; the RP specimens
      were completely embedded and histopathologically evaluated for Gleason grade,
      tumour volume and anatomical extent, and were staged according to the 2002 TNM
      staging criteria. Patients were followed for a median of 39.5 months. BCR was
      defined as two subsequent increasing prostate-specific antigen (PSA) levels of
      >0.10 ng/mL. Kaplan-Meier and proportional hazards regression analyses were used
      to evaluate the univariable and multivariable prognostic effect of tumour stage.
      RESULTS: According to the 2002 TNM staging system, 360 specimens were found to
      have pT2 tumours; 79 (22%) of the RP specimens were staged as pT2a and 281 (78%)
      as pT2c; no pT2b specimens were identified. Patients with unilateral involvement
      (pT2a) had a 5-year risk of BCR of 13%, while those with bilateral involvement
      (pT2c) had a risk of 23% (log rank test, P = 0.056). Patients with pT2c disease
      were more likely to have a larger tumour volume (Mann-Whitney U-test P < 0.001)
      and positive surgical margins (Fishers' exact test, P = 0.001)than those with
      pT2a tumours. Mann-Whitney U-tests showed no differences between the groups for
      preoperative PSA levels (P = 0.167). Also, the RP Gleason score was no different
      between groups (Pearson chi-square, P = 0.807). In the multivariable analyses,
      positive surgical margins appeared to increase the risk of BCR (hazard ratio 4.4,
      95% confidence interval 2.5-7.9); pT2c vs pT2a had only a marginally
      (insignificant) additional effect (1.3, 0.6-2.7). CONCLUSION: The absence of a
      true unilateral pathological T2b tumour in a series of 360 pT2 RP specimens
      questions the relevance of substaging unilateral disease. The limited differences
      in BCR and in pathological features of unilateral vs bilateral pT2 prostate
      cancer justify modifying the TNM staging system to one with no subclassification
      of pT2 disease, or at most as only one subdivision into unilateral (T2a) and
      bilateral (T2b) disease, combining the T2b and T2c substages.

PMID- 18336609
TI  - Can the International Index of Erectile Function distinguish between organic and
      psychogenic erectile function?
AB  - OBJECTIVE: To define the ability of the International Index of Erectile Function
      (IIEF) to differentiate between organic and psychogenic erectile dysfunction
      (ED). PATIENTS AND METHODS: Patients presenting for the evaluation and treatment
      of ED who had penile duplex Doppler ultrasonography (DUS) completed the IIEF
      questionnaire. Accepted ranges of the IIEF EF domain were used to grade baseline
      severity (severe, moderate and mild < or =11, 11-17, 18-25, respectively).
      Accepted criteria were used to define normality on DUS (peak systolic velocity
      >30 cm/s and end-diastolic velocity <5 cm/s). Patients with documented Peyronie's
      disease, hypogonadism and a history of radical prostatectomy were excluded.
      RESULTS: In all, 112 patients were enrolled, with a mean (sd) age and duration of
      ED of 56 (16) and 2 (0.6) years, respectively. The vascular risk-factor profile
      included diabetes in 15%, hypertension in 26% and hyperlipidaemia in 20%. The
      baseline severity of ED was mild, moderate and severe in 28%, 41% and 32% men,
      respectively. All patients had normal testosterone levels. Patients also with a
      normal DUS were diagnosed with psychogenic ED, in 50%, 13% and 17% of men with
      mild, moderate and severe ED by the IIEF, respectively. No patient with venous
      leak had mild ED, and 62% of men with venous leak had severe ED. CONCLUSIONS:
      These results indicate that the IIEF is not completely accurate in
      differentiating between organic and psychogenic ED, and that almost a fifth of
      men in this study population with severe ED by the IIEF had normal erectile
      haemodynamics. These data have potential ramifications for evaluating the
      baseline severity of ED in trials of erectogenic agents.

PMID- 18336610
TI  - Microarray analysis of bladder smooth muscle from patients with myelomeningocele.
AB  - OBJECTIVE: To examine whether gene profiles can provide a molecular evaluation of
      the quality and therapeutic potential in patients with myelomeningocele (MM), by
      comparing genetic profiles of smooth muscle cells (SMCs) from healthy bladders
      and bladders from patients, to identify genes that are over- and under-expressed
      in MM bladder SMCs. MATERIAL AND METHODS: Bladder SM biopsies were obtained from
      'healthy' subjects undergoing bladder surgery for vesico-ureteric reflux and from
      patients with a neurogenic bladder secondary to MM. Bladder SMCs were expanded in
      vitro and total RNA was isolated and hybridized to gene chips to evaluate the
      differential expression levels of 22 283 genes. Differentially expressed genes
      were identified by two methods. In the first analysis, we directly compared raw
      data sets of healthy SMCs to those derived from patients with MM. In the second
      analysis, we indirectly compared healthy SMCs and MM SMCs to a reference file, to
      create a genetic signature of genes that are over- and under-expressed in MM
      SMCs. RESULTS: The direct analysis identified 240 genes that were over-expressed
      and 104 that were under-expressed in MM SMCs. Gene ontology classifications were
      used to identify biological themes and pathways. Genes that were over-expressed
      in MM SMCs were involved in development: mesenchyme homeobox 2 (-fold change,
      9.3); bone morphogenic protein 6 (4.0); fibroblast growth factor 2 (4.8); inhibin
      A (4.2), cartilage oliogomeric matrix protein (9.97); collagen 11A (6); collagen
      5A2 (3) and collagen 1A1 (2.18). The indirect analysis identified 665 genes that
      were over-expressed and 1343 that were under-expressed in MM SMCs. Pathway-based
      analysis of these genetic signatures showed an over-expression of genes involved
      in muscle development and focal adhesion/extracellular matrix interactions. Genes
      that were under-expressed in MM SMCs were mapped to muscle contraction,
      transmission of nerve impulses, and cell-cell adhesion pathways. CONCLUSION: Our
      results are consistent with previous studies showing that MM bladders have an
      excess of extracellular matrix deposition, improper contraction, and are
      developmentally immature relatively to healthy SMCs. The clinical implication of
      microarray analysis of MM SMCs is that it provides potential targets that could
      induce muscle differentiation and inhibit extracellular matrix production.

PMID- 18336611
TI  - Examining lower urinary tract symptom constellations using cluster analysis.
AB  - OBJECTIVE: To gain a better understanding of how patients experience lower
      urinary tract symptoms (LUTS) and to determine whether particular symptoms
      cluster together, as LUTS seldom occur alone. SUBJECTS AND METHODS: A secondary
      analysis of a cross-sectional, population-based survey of adults in Sweden,
      Italy, Germany, UK and Canada was undertaken to examine the presence of LUTS
      groups. Of the 19,165 telephone surveys, 13,519 respondents reported at least one
      LUTS and were included in the analysis. All respondents were asked about the
      presence of 14 LUTS (International Prostate Symptom Score plus seven additional
      LUTS). K-means cluster analyses, a statistical method for sorting objects into
      groups so that similar objects are grouped together, was used to identify groups
      of people based on their symptoms. Men and women were analysed separately. A
      split-half random sample was selected from the dataset so that exploratory
      analyses could be conducted in one half and confirmed in the second. On model
      confirmation, the sample was analysed in its entirety. RESULTS: Included in this
      analysis were 5014 men (mean age 49.8 years; 95% white) and 8505 women (mean age
      50.4 years; 96% white). Among both men and women, six distinct symptom cluster
      groups were identified and the symptom patterns of each cluster were examined.
      For both, the largest cluster consisted of respondents with minimal symptoms
      (i.e. reporting essentially one symptom), 56% of men and 57% of women. The
      remaining five clusters for men and women were labelled based on their
      predominant symptoms. For men, the clusters were nocturia of twice or more per
      night (12%); terminal dribble (11%); urgency (10%); multiple symptoms (9%); and
      postvoid incontinence (5%). For women, the clusters were nocturia of twice or
      more per night (12%); terminal dribble (10%); urgency (8%); stress incontinence
      (8%); and multiple symptoms (5%). The multiple-symptom groups had several and
      varied LUTS, were older, and had more comorbidities. Clusters of terminal dribble
      and male postvoid incontinence had a lower prevalence of all other LUTS, but were
      fairly common (11% and 5% of men). CONCLUSIONS: This analysis provides an
      empirical approach to examining the presentation of multiple LUTS and suggests it
      is possible to identify subgroups of patients with LUTS based on their symptom
      presentation. These analyses need to be replicated to evaluate the clinical
      relevance of these findings.

PMID- 18336612
TI  - Early results of bladder-cancer screening in a high-risk population of heavy
      smokers.
AB  - OBJECTIVE: To report first results of an early bladder-cancer detection
      programme, and to evaluate the detection rate and the diagnostic value of the
      tests used. SUBJECTS AND METHODS: Urine samples of 183 screened subjects with a
      history of smoking of > or =40 pack-years were collected for analysis with a
      urinary dipstick test for haematuria, the nuclear matrix protein-22 test
      (BladderChek, Matritech, Inc., Newton, MA, USA), voided urine cytology and a
      molecular cytology test (UroVysion, Abbott Molecular Inc., Des Plaines, IL, USA).
      Participants with at least one positive test result had a further evaluation
      including cystoscopy and radiological imaging. The subjects' risk factors, test
      results and histological findings were analysed. RESULTS: In all, 75 subjects had
      at least one positive test result and were evaluated further; abnormal
      histological findings were detected in 18 (24% of those who had cystoscopy, 9.8%
      of the original 183), 15 of those in the urinary bladder, with pTaG1 (one),
      carcinoma in situ (two), dysplastic lesions (11) and one an inverted papilloma.
      In the upper urinary tract, two urothelial tumours (pTaG1 and pTxN2G3) and one
      renal cell carcinoma (pT1G2) were detected by computed tomography. In summary,
      six of 183 subjects (3.3%) had a histologically confirmed malignant tumour and
      another 12 (6.6%) were identified with a possible pre-cancerous lesion of the
      urinary tract. The urinary dipstick, BladderChek, cytology and UroVysion detected
      (i.e. were true-positive in) nine (50%), one (6%), seven (39%) and 11 (61%) of
      the 18 tumours found, while they failed to detect nine (50%), 17 (94%), 11 (61%)
      and seven (39%) of these lesions, respectively. Omitting the urine dipstick test,
      the BladderChek, cytology or UroVysion from the test setting could have spared
      40, five, two or one subjects(s) from unnecessary invasive interventions;
      however, three, none, two or six lesions, would have been missed. More positive
      screening tests per subject was associated with a higher probability of a (pre)
      malignant lesion. CONCLUSION: Screening a high-risk group with a history of
      smoking of > or =40 pack-years showed a significant proportion (3.3%) with
      malignancy. These first results are encouraging and warrant continuation of the
      screening programme. In this series the most efficient screening tool was the
      combination of UroVysion, cytology and urinary dipstick testing. Of special
      scientific interest will be the follow-up of those patients with a possible pre
      cancerous lesion.

PMID- 18336613
TI  - Management of advanced prostate cancer: can we improve on androgen deprivation
      therapy?
AB  - Gonadotrophin-releasing hormone (GnRH) agonists are currently the mainstay in the
      management of advanced prostate cancer. Used either as monotherapy or combined
      with antiandrogens, GnRH agonists suppress serum testosterone levels and thus
      slow the growth of the tumour cells that depend on testosterone for growth. GnRH
      agonists have largely replaced orchidectomy in the management of advanced
      prostate cancer, because patients are reluctant to undergo surgical castration.
      However, can we do better in androgen-deprivation therapy? There is some evidence
      to suggest that GnRH agonists do not achieve the level of testosterone
      suppression attained with orchidectomy, or as rapidly, factors which could be
      expected to affect overall survival. Together, these observations highlight the
      need to develop newer agents that can achieve rapid, profound and sustained
      testosterone suppression, equivalent to that with orchidectomy. Preliminary data
      for the GnRH blocker, degarelix, suggest that this new agent might overcome the
      shortcomings associated with GnRH agonists. Further clinical data are therefore
      awaited with much interest.

PMID- 18336615
TI  - Biomechanical analysis of penile erections: penile buckling behaviour under axial
      loading and radial compression.
AB  - OBJECTIVE: To characterize the biomechanics of erectile function, as contrary
      reports have modelled the penis as an isotropic material and state that only
      axial buckling tests can effectively predict penile rigidity; that assumption is
      questioned and an alternative structure proposed and validated. METHODS: Three
      experimental physical cylindrical models of diameters 1.9, 2.54 and 3.81 cm were
      fabricated and the relationship between axial loading and radial compression was
      measured for cylindrical pressures of 8-20 kPa. A finite element analysis (FEA)
      computer model of the penis was constructed to simulate the response of the
      corpora cavernosa to axial and radial loading for differing diameters and lengths
      of the penile shaft. The stresses developed in the tunica albuginea of the
      corporal bodies of the penis during buckling were assessed using a mathematical
      analysis. RESULTS: From the analysis of surface stresses under variable axial
      loading, as the angle of an applied load changes on an isotropic shaft, the
      magnitude of surface stresses varies up to 50 kPa, and for a pressure vessel the
      magnitude of surface stresses varies up to 100 kPa. The FEA model showed that
      nodal displacements were greatest around a ring under radial compression, and for
      the axially loaded model displacements were greatest at the vessel tip under the
      force gauge. All displacements were 0.1-1.0 mm. There was an exponential
      relationship between internal pressure and the axial force required to cause
      buckling in a thin-walled pressure vessel. There was a nearly constant
      relationship between circumferential displacement and internal pressure under
      uniform radial compression. The displacement values on the FEA analysis were
      approximately equal outside of the areas of high stress which were under the load
      of the external device (compressive ring or force gauge) in both cases. Physical
      modelling shows that when a pressurized vessel is under either axial or radial
      load the internal pressure increases. Vessels at high internal pressure require
      more force to cause buckling than vessels at lower internal pressure. The
      circumferential displacement of a vessel under radial compression is higher in
      vessels of lower internal pressure and less in vessels of high internal pressure.
      The size of a vessel also contributes to its ability to be buckled. Smaller
      vessels buckle under smaller load, but the ratio of force required to buckle vs.
      diameter of the cylinder remained constant. CONCLUSIONS: The computer simulations
      show that with slight deviations from perfectly aligned axial loading the
      stresses felt on the walls of cylindrical columns vary considerably, whether they
      are isotropic beams or pressurized vessels. The material properties of the
      tissues within the corpora cause it to behave as a thin-walled pressurized
      vessel, in which the hoop stress and axial stress have a constant relationship
      independent of the length to diameter ratio rather than as an isotropic beam
      where this relationship varies. Patient discomfort and high operator dependency
      further contribute to the inconsistencies of axial loading methods to determine
      penile buckling. Based on the constant relationship between hoop stress and axial
      stress in thin-walled pressurized vessels this study confirms the validity and
      desirability of using radial compression methods to assess penile rigidity in
      lieu of axial loading methods.

PMID- 18336614
TI  - The potential of hormones and selective oestrogen receptor modulators in
      preventing voiding dysfunction in rats.
AB  - OBJECTIVE: To investigate whether oestrogen, selective oestrogen receptor
      modulators (SERMs), and growth hormone (GH) can prevent the development of
      voiding dysfunction in a postpartum postmenopausal rat model of voiding
      dysfunction. MATERIALS AND METHODS: Immediately after spontaneous delivery, nine
      primiparous Sprague-Dawley rats served as uninjured controls (sham group) and 54
      underwent intravaginal balloon dilation. On day 7, the 54 subject rats underwent
      bilateral ovariectomy. A week later, six treatment groups of nine rats were
      randomized to receive: normal saline (injured control group), 17beta-oestradiol
      (E(2)), raloxifene, levormeloxifene, GH, or GH + E(2). The treatment groups
      received daily subcutaneous injections for 3 weeks. The effects of hormone
      treatment were examined by conscious cystometry at the end of the study. Voiding
      dysfunction was defined to include overactive bladder and sphincter deficiency.
      RESULTS: The sham rats had a mean (sd) voiding frequency of 3 (0.87) times in 10
      min and a bladder capacity of 0.43 (0.13) mL with smooth cystometry curves. The
      number of rats in each treatment group (each group contained nine rats) that had
      voiding dysfunction was as follows: E(2), three; raloxifene, six;
      levormeloxifene, four; and controls, four (P > 0.05 among the groups). Only one
      rat in the GH-treated group and no rats in the GH + E(2)-treated group had
      voiding dysfunction, which was significantly less in the GH + E(2)-treated group
      than in the controls (P = 0.041). CONCLUSION: This functional data suggest that
      the development of voiding dysfunction can be prevented by short-term
      administration of GH and GH + E(2) in our rat model. SERMs and E(2) alone seem to
      have no therapeutic effect.

PMID- 18336616
TI  - A comprehensive analysis of transcript signatures of the phosphatidylinositol-3
      kinase/protein kinase B signal-transduction pathway in prostate cancer.
AB  - OBJECTIVE: To assess the gene activities of various important members of the
      phosphatidylinositol 3 kinase (PIK3)/protein kinase B (PKB/Akt) pathway (involved
      in the promotion and regulation of cellular metabolism, proliferation and
      apoptosis) for alterations in prostate carcinoma. PATIENTS, SUBJECTS AND METHODS:
      Using quantitative real-time reverse-transcription polymerase chain reaction, we
      analysed the transcript levels of 12 genes involved in the PIK3/PKB pathway in
      microdissected tumour tissues from 20 patients with varying stages of prostate
      cancer, assessing differences from adjacent normal tissues and from a pool of
      prostate tissues from healthy controls. RESULTS: In cancer samples with a high
      Gleason grade, the PIK3/PKB pathway was principally affected by marked decreases
      in expression over almost all the investigated stages of the pathway. These
      changes were in effectors of the pathway, especially PIK3 p85 alpha (PIK3R1) and
      integrin-linked kinase, and the pathway target fork-head box protein (FOXO)-1A,
      while the transcript quantities of regulators, e.g. phosphatase/tensin homologue
      (PTEN), were decreased in a smaller proportion of the patients. Transcript
      amounts of FOXO-1A and FOXO-3A were significantly higher in normal tumour
      adjacent tissues than in the healthy controls. CONCLUSIONS: Down-regulation of
      the PIK3/PKB pathway by repression of involved effector and regulator genes at
      all stages of the molecular pathway could represent a marker for the formation of
      highly de-differentiated prostate cancers from low-grade tumour foci. Also, parts
      of the pathway are deviant in normal tumour-adjacent tissue; this might represent
      a reaction to neighbouring tumours or be a sign of pre-cancerous biological
      alterations.

PMID- 18336617
TI  - The longitudinal relationship between the systemic inflammatory response,
      circulating T-lymphocytes, interleukin-6 and -10 in patients undergoing
      immunotherapy for metastatic renal cancer.
AB  - OBJECTIVE: To examine the longitudinal relationship between the systemic
      inflammatory response, circulating T-lymphocyte subpopulations, interleukin-6 and
      -10 in patients undergoing immunotherapy for metastatic renal cancer, as the
      inflammation-based Glasgow Prognostic Score (GPS) provides additional prognostic
      information in patients with advanced renal cancer, but the basis of the
      relationship between the systemic inflammatory response and poorer survival is
      not clear, and nor is the effect of immunotherapy on related variables. PATIENTS
      AND METHODS: The study included 23 patients with metastatic renal cancer and
      starting immunotherapy. Samples of blood were drawn for routine laboratory
      analysis and to quantify cytokines using enzyme-linked immunosorbent assays
      before immunotherapy, and repeated after 2 weeks of treatment. RESULTS: Most
      patients had a good performance status, favourable or intermediate Memorial
      Sloane-Kettering Cancer Center (MSKCC) risk scores, and with elevated C-reactive
      protein (>10 mg/L), GPS (1 or 2), interleukin-6 (>4 pg/mL) and interleukin-10
      (>10 pg/mL). Patients who completed one cycle of immunotherapy were more likely
      to have a normal MSKCC (P < 0.05) or GPS (P < 0.05) scores, whilst the percentage
      of lymphocytes was lower (P < 0.05). The MSKCC and the GPS scores did not alter
      significantly during one cycle of immunotherapy. Similarly, leukocyte counts,
      CD4+ and CD8+ T-lymphocytes, interleukin-6 and -10 concentrations did not change
      significantly. CONCLUSIONS: The pretreatment systemic inflammatory response and
      its related lymphopenia are important in determining the tolerance to
      immunotherapy in patients with metastatic renal cancer. Immunotherapy is not
      associated with changes in circulating T-lymphocytes, nor the systemic
      inflammatory response.

PMID- 18336618
TI  - Closing the loop in fishery management: the importance of instituting regular
      independent management review.

PMID- 18336619
TI  - Where's the conservation in conservation genetics?

PMID- 18336620
TI  - Evaluating biodiversity conservation around a large Sumatran protected area.
AB  - Many of the large, donor-funded community-based conservation projects that seek
      to reduce biodiversity loss in the tropics have been unsuccessful. There is,
      therefore, a need for empirical evaluations to identify the driving factors and
      to provide evidence that supports the development of context-specific
      conservation projects. We used a quantitative approach to measure, post hoc, the
      effectiveness of a US$19 million Integrated Conservation and Development Project
      (ICDP) that sought to reduce biodiversity loss through the development of
      villages bordering Kerinci Seblat National Park, a UNESCO World Heritage Site in
      Indonesia. We focused on the success of the ICDP component that disbursed a total
      of US$1.5 million through development grants to 66 villages in return for their
      commitment to stop illegally clearing the forest. To investigate whether the ICDP
      lowered deforestation rates in focal villages, we selected a subset of non-ICDP
      villages that had similar physical and socioeconomic features and compared their
      respective deforestation rates. Village participation in the ICDP and its
      development schemes had no effect on deforestation. Instead, accessible areas
      where village land-tenure had been undermined by the designation of selective
      logging concessions tended to have the highest deforestation rates. Our results
      indicate that the goal of the ICDP was not met and, furthermore, suggest that
      both law enforcement inside the park and local property rights outside the park
      need to be strengthened. Our results also emphasize the importance of
      quantitative approaches in helping to inform successful and cost-effective
      strategies for tropical biodiversity conservation.

PMID- 18336621
TI  - Antihypertensive treatment in elderly hypertensives without a history of stroke
      and the risk of cognitive disorders.
AB  - OBJECTIVES: The role of the antihypertensive therapy in preventing cognitive
      disorders in elderly persons without a history of stroke is a matter of debate.
      This review focuses on the pathogenesis of the cognitive disorders in elderly
      hypertensives and on the risk factors of their occurrence. METHODS: Relevant
      papers were identified by searches in PubMed from 1946 until October 2007, using
      the key words 'vascular risk factors', 'vascular cognitive impairment', 'vascular
      dementia', 'neuroimaging in hypertension' and 'antihypertensive treatment'.
      RESULTS: Blood pressure lowering in elderly patients with long-standing
      hypertension below a certain critical level may increase the risk of cerebral
      hypoperfusion and cognitive decline, particularly in cases with additional
      vascular risk factors. Cerebral white matter lesions have been found in the
      majority of elderly hypertensives. They have been shown to correlate with
      cognitive disorders. CONCLUSIONS: Appropriate neuropsychological assessment and
      follow-up of the cognitive functions could be considered with the aim to
      individualize the antihypertensive therapy and slow down cognitive decline.
      Prospective studies are needed to confirm such a treatment strategy.

PMID- 18336622
TI  - Sequelae following sural nerve biopsy in type 1 diabetic subjects.
AB  - OBJECTIVES: To detect post-operative sequelae of sural nerve biopsy. MATERIALS
      AND METHODS: A questionnaire mailed to type 1 diabetic patients (n = 24;
      male/female 23/1; reply n = 23) 2 years after biopsy. RESULTS: Type 1 diabetic
      patients (age 56 [11]; median [interquartile range]) had a long duration of
      diabetes (DM; 20 [19] years) and all had neuropathy. Three out of 24 patients
      developed infection (two superficial and one deep) and one had a post-operative
      bleeding. Less frequent pain among the patients were reported from one centre.
      About one-third or more of the patients still complained of pain, mostly mild, in
      the biopsy area and paraesthesia in the foot 2 years after surgery. More than two
      thirds of the patients were reluctant for further biopsy; a crucial information
      in drug trial planning. CONCLUSIONS: Sequelae of a sural nerve biopsy occur in
      type 1 DM. The risk for wound infections should be considered.

PMID- 18336623
TI  - Prevalence of CT-detected cerebral abnormalities in an elderly Swedish population
      sample.
AB  - OBJECTIVE: To measure the prevalence of computed tomography (CT)-detected
      cerebral lesions in a population-based sample of elderly persons living in
      Goteborg, Sweden. METHODS: Cerebral CT-scans were performed in the case of 466
      women (mean age 74.3 +/- 5.1 years) and 191 70-year-old men. A single rater
      assessed white matter lesions (WML) using four different scales, lacunar lesions,
      large infarcts, cortical atrophy, and basal ganglia calcifications. RESULTS:
      White matter lesions frequency assessed by different scales ranged between 54.5%
      and 68.5%. Lacunar lesions were detected in 46.7% (30.1% had lacunes >5 mm) and
      cerebral infarcts in 3.0% of participants. Overall, 72.8% of participants
      evidenced cerebral vascular abnormalities. Severe cortical atrophy was more
      common in temporal (6.4%) and frontal (6.7%) lobes, than in parietal (1.7%) and
      occipital (1.1%) lobes. Basal ganglia calcifications were found in 38.7% of
      participants. WML, lacunar lesions, large infarcts, and degree of cortical
      atrophy correlated positively with age. More lacunes, basal ganglia
      calcifications, and occipital lobe atrophy were associated with male gender.
      CONCLUSIONS: Vascular and other brain lesions are very common on CT-scan in an
      elderly population, but large vascular lesions are rare. This study provides the
      first reference for the prevalence of CT-detected abnormalities in an elderly
      Swedish population.

PMID- 18336624
TI  - Pallidal deep brain stimulation in the treatment of Meige syndrome.
AB  - BACKGROUND: Pallidal deep brain stimulation (DBS) of globus pallidus internus
      (Gpi) has emerged as an effective treatment for dystonia. The experience is
      however limited concerning focal dystonias and to date only a few cases of
      pallidal DBS in the treatment of Meige syndrome have been published.
      METHODS/RESULTS: We here present a patient with Meige syndrome in whom unilateral
      pallidal DBS failed to improve the axial symptoms, but bilateral stimulation
      resulted in a major improvement. The Burke-Fahn-Marsden score (BFM) improved by
      71.5% and the patient's blepharospasm was abolished. CONCLUSIONS: The results
      suggest bilateral pallidal DBS may be an effective treatment for Meige syndrome.

PMID- 18336625
TI  - The effects of methylprednisolone and mitoxantrone on CCL5-induced migration of
      lymphocytes in multiple sclerosis.
AB  - OBJECTIVES: Chemokines are involved in migration of inflammatory cells to the
      central nervous system (CNS) in multiple sclerosis (MS). The aim of this study
      was the analysis of the impact of MS treatment on CCL5-induced migration of
      leukocyte subpopulations. MATERIAL AND METHODS: Migration of lymphocytes and
      monocytes from blood of MS patients treated with methylprednisolone (MP) or
      mitoxantrone (MTX) was analysed in a chemotaxis chamber. RESULTS: CCL5-induced
      migration of lymphocytes from untreated MS patients was significantly increased
      over controls. The treatment of MS with MP and MTX reduced this chemotaxis. The
      plasma level of CCL5 was increased in MS patients before treatment and was also
      significantly decreased in the treatment of MS with MP and MTX. CONCLUSIONS: This
      observation supports the hypothesis that in MS, chemokine CCL5 may induce
      migration of leukocytes to the CNS and suggests that treatment of the disease
      with MP and MTX may reduce this migration.

PMID- 18336626
TI  - Diagnostic yield of cerebral imaging in patients with acute confusion.
AB  - OBJECTIVE: Acute confusion (AC) is a frequent reason for hospital admission in
      elderly patients. Although in majority of cases the cause is a systemic disorder
      (e.g., dehydration or septicaemia), patients are frequently subjected to cerebral
      imaging. This study was undertaken to find clinical predictors of normal cerebral
      computed tomography (CCT) or magnetic resonance imaging (MRI) scans in AC.
      METHODS: Retrospective study of 294 patients admitted with AC of unknown origin,
      of whom 178 received cerebral imaging. RESULTS: The rate of pathological imaging
      studies was 14%. The best single predictor of a normal brain scan was the absence
      of focal signs. Patients without focal abnormalities and either fever or
      dehydration had a probability of 0.96 of having a normal CCT or MRI. In demented
      patients without focal signs, the predictive value for a normal brain scan was
      0.98, and if either patients with drowsiness were excluded or the existence of
      fever or dehydration was added as a selection criterion, all patients had normal
      scans. CONCLUSIONS: Patients with AC without focal signs and with either evidence
      for a medical aetiology of delirium or prediagnosed dementia are at a very low
      risk of having focal lesions in their CCT or MRI.

PMID- 18336627
TI  - Neuromyelitis optica: a distinct demyelinating disease of the central nervous
      system.
AB  - OBJECTIVES: We review and discuss the pathogenesis, epidemiology, diagnosis as
      well as recent advances in the treatment of NMO. We also highlight areas of
      future research. METHODS: A review was carried out on reports drawn from MEDLINE
      until 2007. RESULTS: Neuromyelitis optica (NMO) is a relative uncommon
      demyelinating disease of the central nervous system (CNS) that preferentially
      affects the optic nerves and spinal cord. NMO follows an unpredictable course,
      being either monophasic or relapsing. The relapsing form of NMO primarily affects
      women with onset varying from childhood to adults in their 40s or elderly. Until
      recently, NMO was considered to be a variant of multiple sclerosis. However, in
      contrast to multiple sclerosis, NMO attacks are not mediated by T cells but
      rather by B cells and NMO-immunoglobulin G antibodies that target aquaporin-4.
      Humoral immune mechanisms, including complement activation plays an important
      role in the pathogenesis of NMO. At present, parenteral corticosteroids are
      widely employed as first-line treatment of optic neuritis and myelitis attacks,
      whereas therapeutic plasmapheresis is applied in the case of corticosteroids
      failure. Various strategies for the prevention of NMO relapses have been employed
      in small case series with modest activity. CONCLUSION: Recent advances in the
      clinical, neuroimaging, laboratory and pathological hallmarks have established
      that NMO is a distinct demyelinating disease of the CNS.

PMID- 18336628
TI  - Stereological characteristics of the equine accessory nerve.
AB  - Stereological techniques have been increasingly employed for assessment and
      characterization of neuromuscular diseases in humans and animals. As an adjunct
      to histopathology, morphometrical algorithms provide quantitative evidence of the
      peripheral nerve composition, thereby shedding light on its fibre characteristics
      and basic electrophysiological properties. In the horse, stereological
      investigations already have focussed on the recurrent laryngeal, deep peroneal
      and lateral palmar nerves (LPN). Of these, only the latter is suitable for taking
      biopsies in clinical settings, however, it does not contain any motor fibres and
      Ia-afferents. On account of its virtually mixed fibre qualities, most researchers
      today recommend the cervical branch of the equine accessory nerve (AN) for
      harvesting diagnostic samples. Thus, the present study was carried out to gain
      morphometrical proof of the AN composition and to obtain stereological base
      values in healthy individuals using state-of-the-art technology. All parameters
      were compared to the common peroneal nerve (CPN), known to harbour all myelinated
      fibre classes. As this second biopsy site is located farther distally to the
      neuro-axis, attention was paid to possible length-dependent features. Taken
      together, digital image analysis could be accurately applied on all AN samples.
      Stereology supported the histological and clinical evidence that the AN contains
      all myelinated fibre types. The huge range and scatter of fibre counts and
      density (3351-17,812/mm(2)) per fascicle were comparable to that measured in the
      equine common peroneal, deep peroneal, lateral palmar and recurrent laryngeal
      nerves. Similar to those, fibre diameter distribution was bimodal with slow Abeta
      and Agamma-mechanoceptor afferents outnumbering large myelinated Aalpha-fibres
      by a factor of about 1.5. With a g-ratio at 0.55 +/- 0.001, the overall degree of
      myelination in the AN is highly consistent and insignificantly ranges between
      that of the equine common peroneal and LPNs. Apart from this subtle deviation, a
      statistically relevant difference between the more proximal AN and the distal CPN
      could not be documented. By obtaining morphometrical standard parameters and even
      more sophisticated distribution indices, stereology is a valuable tool for
      detection of subtle changes that are likely to escape from the investigators'
      eyes. The AN serves as a reliable source for advanced peripheral nerve research
      and should be accompanied by farther distal nerve probes for assessment of
      neuropathies that present with a proximodistal gradient.

PMID- 18336629
TI  - Effects of developmental exposure to ethanol on Caenorhabditis elegans.
AB  - BACKGROUND: We investigated the effects of chronic ethanol exposure on physical
      development, reproduction, and life expectancy of Caenorhabditis elegans, a
      microscopic nematode worm. It has a small nervous system of 302 neurons and a
      short lifespan of 2 to 3 weeks. METHODS: In this study, the worms were
      chronically exposed to varying concentrations of ethanol for different periods of
      their life: for their entire lifespan, during larval development only, and during
      adulthood only. In addition, the worms were exposed to ethanol acutely during
      different stages of embryonic development. RESULTS: Chronic exposure to ethanol
      during larval development temporarily delayed physical growth, slowed
      development, delayed the onset of reproductive maturity, and decreased both
      reproductive fecundity and longevity. Chronic exposure to ethanol beginning when
      worms completed development and reached reproductive maturity resulted in reduced
      C. elegans body length, decreased reproductive fecundity, and life expectancy.
      Finally, acute embryonic exposure of C. elegans eggs to high concentrations of
      ethanol at different stages of development resulted in a lower probability of
      exposed eggs hatching into larval worms depending on when eggs were exposed
      during development. Furthermore, some of the worms that did hatch displayed
      distinct physical dysmorphologies as a consequence of acute ethanol exposure
      during embryonic development. CONCLUSIONS: These data suggest that exposing C.
      elegans to ethanol during critical development periods results in characteristic
      phenotypic outcomes. Thus, C. elegans offers a novel model for exploring the
      mechanisms by which ethanol exposure affects development.

PMID- 18336630
TI  - Alteration in G proteins and prolactin levels in pituitary after ethanol and
      estrogen treatment.
AB  - BACKGROUND: Chronic administration of ethanol increases plasma prolactin levels
      and enhances estradiol's mitogenic action on the lactotropes of the pituitary
      gland. The present study was conducted to determine the changes in the pituitary
      levels of G proteins during the tumor development following alcohol and ethanol
      treatments. METHODS: Using ovariectomized Fischer-344 female rats, we have
      determined ethanol and estradiol actions at 2 and 4 weeks on pituitary weight and
      pituitary cell contents of prolactin, Gs. Gq11, Gi1, Gi2, and Gi3 proteins.
      Western blots were employed to measure protein contents. RESULTS: Ethanol
      increased basal and estradiol-enhanced wet weight and the prolactin content in
      the pituitary in a time-dependent manner. Chronic exposure of estradiol increased
      the levels of Gs protein in the pituitary. Unlike estradiol, ethanol exposure did
      not show significant effect on the basal level of Gs protein, but moderately
      increased the estradiol-induced levels of this protein. Estradiol exposure
      enhanced Gq11 protein levels in the pituitary after 2 and 4 weeks, while ethanol
      treatment failed to alter these protein levels in the pituitary in control
      treated or estradiol-treated ovariectomized rats. In the case of Gi1, estradiol
      but not ethanol increased the level of this protein at 4 weeks of treatment.
      However, estradiol and ethanol alone reduced the levels of both Gi2 and Gi3
      proteins at 2 and 4 weeks of treatment. Ethanol also significantly reduced the
      estradiol-induced Gi2 levels at 4 weeks and Gi3 level at 2 and 4 weeks.
      CONCLUSIONS: These results confirm ethanol's and estradiol's growth-promoting and
      prolactin stimulating actions on lactotropes of the pituitary and further provide
      evidence that ethanol and estradiol may control lactotropic cell functions by
      altering expression of specific group of G proteins in the pituitary.

PMID- 18336631
TI  - Acute alcohol intoxication increases REDD1 in skeletal muscle.
AB  - BACKGROUND: The mechanism by which acute alcohol (EtOH) intoxication decreases
      basal muscle protein synthesis via inhibition of the Ser/Thr kinase mammalian
      target of rapamycin (mTOR) is poorly defined. In this regard, mTOR activity is
      impaired after over expression of the regulatory protein REDD1. Hence, the
      present study assessed the ability of REDD1 as a potential mediator of the EtOH
      induced decrease in muscle protein synthesis. METHODS: The effect of acute EtOH
      intoxication on REDD1 mRNA and protein was determined in striated muscle of rats
      and mouse myocytes using an RNase protection assay and Western blotting,
      respectively. Other components of the mTOR signaling pathway were also assessed
      by immunoblotting. For comparison, REDD1 mRNA/protein was also determined in the
      muscle of rats chronically fed an alcohol-containing diet for 14 weeks. RESULTS:
      Intraperitoneal (IP) injection of EtOH increased gastrocnemius REDD1 mRNA in a
      dose- and time-dependent manner, and these changes were associated with
      reciprocal decreases in the phosphorylation of 4E-BP1, which is a surrogate
      marker for mTOR activity and protein synthesis. No change in REDD1 mRNA was
      detected in the slow-twitch soleus muscle or heart. Acute EtOH produced
      comparable increases in muscle REDD1 protein. The EtOH-induced increase in
      gastrocnemius REDD1 was independent of the route of EtOH administration (oral vs.
      IP), the nutritional state (fed vs. fasted), gender, and age of the rat. The
      nonmetabolizable alcohol tert-butanol increased REDD1 and the EtOH-induced
      increase in REDD1 was not prevented by pretreatment with the alcohol
      dehydrogenase inhibitor 4-methylpyrazole. In contrast, REDD1 mRNA and protein
      were not increased in the isolated hindlimb perfused with EtOH or in C2C12
      myocytes incubated with EtOH, under conditions previously reported to decrease
      protein synthesis. Pretreatment with the glucocorticoid receptor antagonist RU486
      failed to prevent the EtOH-induced increase in REDD1. Finally, the EtOH-induced
      increase in REDD1 was not associated with altered formation of the TSC1*TSC2
      complex or the phosphorylation of TSC2 which is down stream in the REDD1 stress
      response pathway. In contradistinction to the changes observed with acute EtOH
      intoxication, REDD1 mRNA/protein was not changed in gastrocnemius from chronic
      alcohol-fed rats despite the reduction in 4E-BP1 phosphorylation. CONCLUSIONS:
      These data indicate that in fast-twitch skeletal muscle (i) REDD1 mRNA/protein is
      increased in vivo by acute EtOH intoxication but not in response to chronic
      alcohol feeding, (ii) elevated REDD1 in response to acute EtOH appears due to the
      production of an unknown secondary mediator which is not corticosterone, and
      (iii) the EtOH-induced decrease in protein synthesis can be dissociated from a
      change in REDD1 suggesting that the induction of this protein is not responsible
      for the rapid decrease in protein synthesis after acute EtOH administration or
      for the development of alcoholic myopathy in rats fed an alcohol-containing diet.

PMID- 18336632
TI  - Ethanol inhibits functional activity of the human intestinal dipeptide
      transporter hPepT1 expressed in Xenopus oocytes.
AB  - BACKGROUND: The pathological effects of high alcohol (ethanol) consumption on
      gastrointestinal and hepatic systems are well recognized. However, the effects of
      ethanol intake on gastric and intestinal absorption and transport systems remain
      unclear. The present study investigates the effects of ethanol on the human
      peptide transporter 1 (hPepT1) which mediates the transport of di-and tripeptides
      as well as several orally administered peptidomimetic drugs such as beta-lactam
      antibiotics (e.g., penicillin), angiotensin-converting enzyme inhibitors, the
      anti-neoplastic agent bestatin, and prodrugs of acyclovir. METHODS: Xenopus
      oocytes were injected with hPepT1 cRNA and incubated for 3 to 10 days. Currents
      induced by glycyl-sarcosine (Gly-Sar), Ala-Ala (dipeptides), penicillin and
      enalapril measured in the presence or absence of ethanol were determined using an
      8-channel 2-electrode voltage clamp system, with a membrane potential of -70 mV
      and 11 voltage steps of 100 milliseconds (from +50 mV to -150 mV in -20 mV
      increments). RESULTS: Ethanol (200 mM) inhibited Gly-Sar and Ala-Ala currents by
      42 and 30%, respectively, with IC(50)s of 184 and 371 mM, respectively. Ethanol
      reduced maximal transport capacity (I(max)) of hPepT1 for Gly-Sar without
      affecting Gly-Sar binding affinity (K(0.5) and Hill coefficient). Penicillin- and
      enalapril-induced currents were significantly less than those induced by
      dipeptides and were not inhibited by ethanol. CONCLUSION: Ethanol significantly
      reduced transport of dipeptides via a reduction in transport capacity, rather
      than competing for binding sites in hPepT1. Ethanol inhibition or alteration of
      transport function may be a primary causative factor contributing to both the
      nutritional deficits as well as the immunological deficiencies that many
      alcoholics experience including alcohol liver disease and brain damage.

PMID- 18336633
TI  - Secular trends in the lifetime prevalence of alcohol dependence in the United
      States: a re-evaluation.
AB  - BACKGROUND: U.S. epidemiologic surveys have consistently found higher lifetime
      prevalence of alcohol dependence among younger subjects than among older groups.
      Because lifetime prevalence is cumulative, such patterns are suggestive of strong
      secular trends; i.e., more-recently born subjects have developed more disease in
      a shorter period of time than their elders. However, it remains unclear whether
      such patterns truly reflect secular trends or are confounded by age-dependent
      factors such as differential recall, differential mortality, and other effects.
      METHODS: Using data from 2 large, national epidemiological surveys, a repeated
      cross-sectional analysis was conducted to compare lifetime prevalence of alcohol
      dependence across temporally adjacent birth cohorts surveyed at the same age,
      thus enabling estimates of cross-cohort differences while controlling for age
      related factors. RESULTS: In contrast with results from single cross-sectional
      analyses, there were few significant cross-cohort differences among groups of men
      compared at similar ages. On the other hand, women born between 1954 and 1963
      were at 1.2-fold higher odds for lifetime drinking, and those who drank were at
      1.5-fold higher odds for lifetime alcohol dependence, compared with the
      immediately preceding birth cohort (1944 to 1953). The 1944 to 1953 cohort was
      also at elevated odds for lifetime drinking compared with their predecessors
      (1934 to 1943). These results were largely due to changes among White and
      Hispanic women. CONCLUSIONS: These results suggest that there have been
      substantial secular increases in drinking and alcohol dependence among women, but
      not men. Analyses of single cross-sectional studies may tend to over-estimate
      secular trends by failing to account for age-dependent effects. Nonetheless,
      secular increases in drinking and alcohol dependence among women are evident
      after taking age-related factors into account.

PMID- 18336634
TI  - Maternal risk factors for fetal alcohol syndrome and partial fetal alcohol
      syndrome in South Africa: a third study.
AB  - OBJECTIVES: This is a third exploration of risk factors for the two most severe
      forms of fetal alcohol spectrum disorders (FASD), fetal alcohol syndrome (FAS)
      and Partial FAS (PFAS), in a South African community with the highest reported
      prevalence of FAS in the world. METHODS: In a case control design, interview and
      collateral data concerning mothers of 72 first grade children with FAS or PFAS
      are compared with 134 randomly selected maternal controls of children from the
      same schools. RESULTS: Significant differences were found between the mothers of
      FASD children and controls in socio-economic status, educational attainment, and
      a higher prevalence of FASD among rural residents. The birth order of the index
      children, gravidity, and still birth were significantly higher among mothers of
      FASD children. Mothers of children with a FASD are less likely to be married and
      more likely to have a male partner who drank during the index pregnancy. Current
      and gestational alcohol use by mothers of FASD children is bingeing on weekends,
      with no reduction in drinking reported in any trimester in 75 to 90% of the
      pregnancies that resulted in an FAS child or during 50 to 87% of PFAS-producing
      pregnancies. There was significantly less drinking among the controls in the
      second and third trimesters (11 to 14%). Estimated peak blood alcohol
      concentrations (BAC)s of the mothers of PFAS children range from 0.155 in the
      first trimester to 0.102 in the third, and for mothers of FAS children the range
      is from 0.197 to 0.200 to 0.191 in the first, second, and third. Smoking
      percentage during pregnancy was significantly higher for mothers of FASD children
      (82 to 84%) than controls (35%); but average quantity smoked is low in the 3
      groups at 30 to 41 cigarettes per week. A relatively young average age of the
      mother at the time of FAS and PFAS births (28.8 and 24.8 years respectively) is
      not explained by early onset of regular drinking (mean = 20.3 to 20.5 years of
      age). But the mean years of alcohol consumption is different between groups,
      16.3, 10.7, and 12.1 years respectively for mothers of FAS, FASD, and drinking
      controls. Mothers of FAS and PFAS children were significantly smaller in height
      and weight than controls at time of interview. The child's total dysmorphology
      score correlates significantly with mother's weight (-0.46) and BMI (-0.39).
      Bivariate correlations are significant between the child's dysmorphology and
      known independent demographic and behavioral maternal risk factors for FASD:
      higher gravidity and parity; lower education and income; rural residence; drinks
      consumed daily, weekly, and bingeing during pregnancy; drinking in all
      trimesters; partner's alcohol consumption during pregnancy; and use of tobacco
      during pregnancy. Similar significant correlations were also found for most of
      the above independent maternal risk variables and the child's verbal IQ, non
      verbal IQ and behavioral problems. CONCLUSIONS: Maternal data in this population
      are generally consistent with a spectrum of effects exhibited in the children.
      Variation within the spectrum links greater alcohol doses with a greater severity
      of effects among children of older and smaller mothers of lower socio economic
      status in their later pregnancies. Prevention is needed to address known maternal
      risk factors for FASD in this population.

PMID- 18336635
TI  - Naltrexone and cognitive behavioral therapy for the treatment of alcohol
      dependence: do sex differences exist?
AB  - BACKGROUND: Sex differences in regards to pharmacotherapy for alcoholism is a
      topic of concern following publications suggesting naltrexone, one of the longest
      approved treatments of alcoholism, is not as effective in women as in men. This
      study was conducted by combining 2 randomized placebo controlled clinical trials
      utilizing similar methodologies and personnel in which the data was amalgamated
      to evaluate sex effects in a reasonable sized sample. METHODS: A total of 211
      alcoholics (57 female and 154 male) were randomized to the naltrexone/cognitive
      behavorial thearpy (CBT) or placebo/CBT arm of the 2 clinical trials analyzed.
      Baseline variables were examined for differences between sex and treatment groups
      via ANOVA for continuous variable or chi-squared test for categorical variables.
      All initial outcome analysis was conducted under an intent-to-treat analysis
      plan. Effect sizes for naltrexone over placebo were determined by Cohen's D (d).
      RESULTS: The effect size of naltrexone over placebo for the following outcome
      variables was similar in men and women [% days abstinent (PDA) d = 0.36, % heavy
      drinking days (PHDD) d = 0.36, and total standard drinks (TSD) d = 0.36]. Only
      for men were the differences significant secondary to the larger sample size (PDA
      p = 0.03; PHDD p = 0.03; TSD p = 0.04). There were a few variables (GGT at week
      12 change from baseline to week-12: men d = 0.36, p = 0.05; women d = 0.20, p =
      0.45 and drinks per drinking day: men d = 0.36, p = 0.05; women d = 0.28, p =
      0.34) where the naltrexone effect size for men was greater than women. In women,
      naltrexone tended to increase continuous abstinent days before a first drink
      (women d = 0.46, p = 0.09 and men d = 0.00, p = 0.44). CONCLUSIONS: The effect
      size of naltrexone over placebo appeared similar in women and men in our hands
      suggesting the findings of sex differences in naltrexone response might have to
      do with sample size and/or endpoint drinking variables rather than any inherent
      pharmacological or biological differences in response.

PMID- 18336636
TI  - Restraint stress and ethanol consumption in two mouse strains.
AB  - BACKGROUND: This study examined the interaction between restraint stress and
      ethanol drinking in mice that consume low and high amounts of ethanol. METHODS:
      Two strains of mice (129SVEV and C57BL/6J) underwent 1 hour of restraint stress
      twice per day for 4 days in the presence of a CRF-1 receptor antagonist, a
      glucocorticoid receptor antagonist or vehicle. Ethanol preference and consumption
      were assessed using a two bottle choice design. In another study, mice were
      implanted with pellets containing corticosterone; ethanol preference and
      consumption were assessed using a two bottle choice design. RESULTS: Restraint
      stress significantly increased ethanol preference and consumption in 129SVEV mice
      but not in C57BL/6J mice. Then 129SVEV mice underwent the identical stress
      procedure; however, mice received either the CRF-1 receptor antagonist, R121919
      (15 or 20 mg/kg, ip) or vehicle 30 minutes prior to stress. R121919 did not block
      the stress-induced change in ethanol preference despite causing a significant
      blunting in the HPA axis. Negative results were also obtained using the CRF-1
      receptor antagonist, Antalarmin (20 mg/kg, ip). In another study, 129SVEV mice
      were administered either the glucocorticoid receptor antagonist Mifepristone (25,
      50 or 100 mug/kg, ip) or vehicle under the same procedure. Mifepristone did not
      alter ethanol preference. Moreover, the three receptor antagonist did not alter
      nonstress ethanol consumption either. In the last study, both mouse strains
      underwent active or sham adrenalectomy, then pellets containing corticosterone or
      placebo were implanted and preference for ethanol versus water was tested.
      Corticosterone administration decreased ethanol consumption in a strain-dependent
      manner. CONCLUSION: These data show the restraint model for stress can modestly
      increase ethanol consumption in 129SVEV mice but not in C57BL/6J mice.
      Pharmacologic manipulation of CRF and corticosterone did not blunt baseline or
      stress-induced change in ethanol preference nor did administration of
      corticosterone mimic the effects of restraint stress on ethanol consumption.
      These findings suggest the mechanism responsible for increasing ethanol
      consumption in this model is independent of the HPA axis and extra-hypothalamic
      CRF.

PMID- 18336637
TI  - Early ethanol consumption predicts relapse-like behavior in adolescent male rats.
AB  - BACKGROUND: Alcohol abuse disorders emerge over time with repeated consumption of
      ethanol, but not all ethanol drinkers develop these disorders. There are pre
      existing characteristics that indicate which drinkers are most likely to abuse
      alcohol. Adolescence, novelty seeking, and high stress reactivity are among the
      characteristics of the most vulnerable individuals. In addition, an individual's
      response to his or her first exposure to the drug influences future consumption.
      We assessed an array of behavioral and hormonal characteristics in adolescent (28
      day-old) male rats before exposure to ethanol, and then determined which rats
      were most prone to high levels of alcohol drinking. METHODS: The assessments
      consisted of measures of anxiety (elevated plus maze), response to novelty (open
      field locomotion, novel object exploration), and circulating corticosterone
      levels after mild restraint and after the elevated plus maze task. After this
      test battery, the rats were placed in lickometer cages nightly (5 pm to 9 am) for
      evaluation of fluid consumption. Rats were first habituated to the cages with
      water in the lickometer bottles, and then given 10% (v/v) ethanol for 3 nights as
      the only available fluid. After this forced ethanol exposure, the rats were
      allowed to choose between 8% ethanol and water for 10 consecutive nights. After 2
      nights of abstinence, the rats were again placed in the lickometer cages and
      given a choice between 8% ethanol and water to assess ethanol consumption in
      response to alcohol deprivation, a measure of relapse-like behavior. RESULTS:
      Ethanol consumption on the third day of forced consumption was significantly
      correlated with ethanol consumption on days 8 to 10 of the choice phase, which in
      turn was significantly correlated to relapse-like consumption. Preference for
      ethanol was also significantly correlated with early consumption. Novel object
      exploration, open field activity, open arm time in the elevated plus maze,
      initial water consumption, and circulating corticosterone levels did not
      significantly predict deprivation-stimulated consumption. CONCLUSIONS: These
      results suggest that consumption during early exposure to ethanol establishes a
      pattern leading to development of increased alcohol consumption and preference in
      adolescent male rats. In addition, they represent an animal model of the well
      described observation that humans who consume large quantities of ethanol during
      early exposure are the most likely to repeat heave drinking behavior.
      Furthermore, early consumption is distinct from novelty seeking, anxiety, and
      stress hormone levels which are also thought to contribute to vulnerability to
      alcoholism.

PMID- 18336638
TI  - Surrogate alcohols and their metabolites modify histone H3 acetylation:
      involvement of histone acetyl transferase and histone deacetylase.
AB  - BACKGROUND: Ethanol increases histone H3 acetylation in the rat liver. However,
      the effect of other carbon chain length alcohols, consumed as surrogate alcohols
      and used in industry, on H3 acetylation is unknown. Hence, we investigated the
      effect of these alcohols on histone H3 acetylation, cell toxicity and HAT and
      HDAC activity. METHODS: Primary cultures of rat hepatocytes were incubated with
      selected concentration (40 mM) of different chain length alcohols with or without
      inhibitors of alcohol metabolizing enzymes. Cells were also treated with low
      concentration (2.5 mM) of 1-propanol or 1-butanol or isopentanol, with or without
      40 mM ethanol for 24 hours. Effects of the metabolites of these alcohols were
      also studied. Cytotoxicity was determined by lactate dehydrogenase (LDH) release
      and mitochondrial activity (MTT assay). The degree of histone H3 acetylation at
      specific lysine residues were monitored by western bloting using site specific
      antibodies. Histone acetyltransferase (HAT) and histone deacetylase (HDAC)
      activities were measured by enzyme-linked immunosorbent assay (ELISA) and
      colorimetric assay respectively. RESULTS: Alcohols with increasing carbon chain
      length exhibited a variable effect on the ratio of acetylated lys9 histone H3 to
      beta-actin. A graded increase (methanol < ethanol < 1-propanol < 1-butanol)
      followed by a gradual decrease (1-butanol > 1-pentanol > 1-hexanol > 1-octanol)
      in the ratio was observed. Other lysine sites were not affected. HAT activation
      also corresponded to the acetylation profile. These alcohols or their metabolites
      did not significantly alter HDAC activity in the hepatocytes. Low concentration
      (2.5 mM) of 1-propanol alone did not affect acetylation, but sensitized the
      ethanol induced H3 acetylation at lysine 9 (H3AcK9). 1-Butanol and isopentanol
      also increased the response of ethanol induced H3AcK9. Alcohol metabolizing
      inhibitors attenuated ethanol and propanol induced increase in H3AcK9. Carboxylic
      acid metabolites of these alcohols also increased HAT activity and histone H3
      acetylation at lysine 9. Propionate and butyrate modestly inhibited HDAC activity
      in an in vitro assay. CONCLUSIONS: Surrogate alcohols modulate H3AcK9 via
      increasing HAT activity and this is dependent on their metabolism. Furthermore,
      alcohol metabolites also increased H3AcK9, but in contrast, exhibit both HAT
      activation and HDAC inhibition.

PMID- 18336639
TI  - The -308 TNFalpha gene polymorphism in severe acute alcoholic hepatitis:
      identification of a new susceptibility marker.
AB  - BACKGROUND: This study investigated whether genetic polymorphisms in the tumor
      necrosis factor alpha (TNFalpha) gene's promoter region play a role in severe
      acute alcoholic hepatitis (AAH). METHODS: One-hundred and fifty patients (58 AAH
      patients, 45 cirrhosis group free-AAH, 47 healthy group) were genotyped for 3
      TNFalpha polymorphisms (-238, -308, -863) using a polymerase chain reaction
      restriction fragment length polymorphism technique. Serum TNFalpha levels were
      determined. RESULTS: The TNFalpha-308 allele A frequency was significantly lower
      in AAH group (0.09), than cirrhosis (0.28) (p < 0.001), and healthy groups (p <
      0.001). The TNFalpha-308 A/G, A/A genotypes were significantly lower in AAH
      group, than cirrhosis (p = 0.005), and healthy groups (p < 0.001). For AAH group,
      there were no clinical, biological, and serum TNFalpha differences between the 
      308 G/G and A/G, A/A genotype patients, apart higher transaminase in the former
      group (p = 0.02). AAH and cirrhosis groups did not differ for the frequency of
      TNFalpha-238, -863 polymorphisms. The specific genotype did not appear to have
      any influence on the therapeutic response following corticotherapy or
      posttreatment 6-month survival. In the AAH group, nonsurvivors had higher
      TNFalpha levels than survivors (7.9 +/- 8.8 vs. 3.3 +/- 1.6 pg/ml, p = 0.01).
      CONCLUSIONS: These results attest to the involvement of TNFalpha-related genetic
      factors in susceptibility to AAH.

PMID- 18336640
TI  - Fingerprint profile of alcohol-associated heart failure in human hearts.
AB  - BACKGROUND: Excessive alcohol consumption is recognized as a cause of left
      ventricular dysfunction and leads often to alcohol-induced heart failure. It is
      thought that 36% of all cases of dilated cardiomyopathy are due to excessive
      alcohol intake. In addition, since chronic alcohol-consumption is a social
      behavior that is not always clearly self-reported clinically, it has been
      difficult to diagnose alcohol-induced heart failure versus heart failure due to
      idiopathic dilated cardiomyopathy (IDCM). Interestingly, both diseases are
      associated with left ventricular dysfunction and congestive heart failure.
      METHODS: We have created a human heart failure cDNA array for IDCM from
      nonfailing and failing human hearts. The array contains 1,143 heart specific
      oligonucleotide probes. This array was used to screen RNA samples from transplant
      recipients and organ donors with alcohol-related heart failure. RESULTS: Our
      study shows that alcohol-induced heart failure has a "specific fingerprint"
      profile of de-regulated genes. This profile can differentiate patients with pure
      alcohol-induced heart failure from patients with heart failure from IDCM with
      alcohol as a complicating or contributing factor. Furthermore, the pattern of
      gene de-regulation suggests a pivotal role for changes in matrix, cytoskeletal,
      and structural proteins in the development of clinical heart failure resulting
      from excessive alcohol consumption. CONCLUSIONS: We report for the first time a
      genomic "fingerprint" profile of de-regulated genes associated with human alcohol
      induced heart failure. We conclude that the pathogenesis of alcohol-induced heart
      failure in humans is likely related to changes in architectural (e.g.
      cytoskeletal), matrix, and/or structural proteins. The reversibility of the
      disease upon cessation of alcohol consumption makes this a likely pathogenetic
      mechanism. Nevertheless, there is a point at which extracellular as well as
      cellular changes result in irreversible heart failure.

PMID- 18336641
TI  - Vitamin D and child health: some emerging issues.

PMID- 18336642
TI  - Dietary aspects of pregnant women in rural areas of Northern India.
AB  - The aim of this article is to document the current dietary profile of pregnant
      women in rural areas of Delhi. In order to explore the diet the combination of
      quantitative (24-h recall method) and qualitative methods (food frequency method)
      were used. The mean intake of macronutrients and micronutrients, namely, iron,
      folic acid and Vitamin C which play an important role in the pathophysiology of
      nutritional anaemia during pregnancy was calculated from the foodstuffs, using
      Nutritive Value of Indian Foods. The preferences and avoidance of various foods
      by the pregnant women were also elicited. The data were analysed using Epi Info
      3.4. The intake of calories, protein, iron, folic acid and Vitamin C was found to
      be less than the recommended dietary allowance in 100%, 91.2%, 98.2%, 99.1% and
      65.8% of pregnant women respectively. Folic acid intakes were significantly lower
      in younger, primiparous and poorly educated women from low-income families.
      Vitamin C intake was lower among non-Hindus only. The overall data suggested the
      presence of food gap rather than isolated deficiency of any particular nutrient.

PMID- 18336643
TI  - Variation in breastfeeding behaviours, perceptions, and experiences by
      race/ethnicity among a low-income statewide sample of Special Supplemental
      Nutrition Program for Women, Infants, and Children (WIC) participants in the
      United States.
AB  - The objective of this study was to examine how breastfeeding behaviours,
      perceptions and experiences vary by race/ethnicity among a low-income sample in
      the USA. Bilingual interviewers conducted a cross-sectional telephone survey of
      767 white, African American or Hispanic mothers who received the Special
      Supplemental Nutrition Program for Women, Infants, and Children (WIC). Rates of
      breastfeeding initiation and duration varied by race/ethnicity. Hispanic mothers
      were more likely to initiate breastfeeding than African American (91% vs. 65%) or
      white (61%) mothers. Hispanic mothers breastfed longer (mean 5 months) than
      either African American (mean 3.5 months) or white (mean 3 months) mothers. The
      most common reason for not breastfeeding was fear of difficulty or pain during
      breastfeeding (35.6%). Among mothers who did not initiate breastfeeding, African
      American and white mothers were more likely than Hispanic mothers to report
      perceptions of breastfeeding difficulty or pain, and Hispanic mothers were more
      likely than African American and white mothers to report perceptions of infant
      breast rejection. The most common reason reported for breastfeeding cessation was
      not having enough milk (23.4%). Hispanic mothers were more likely than African
      American and white mothers to cite perceptions of milk insufficiency and infant
      breast refusal than concerns regarding breast discomfort or pain. African
      American mothers were more likely than white mothers to report cessation to
      return to work. In conclusion, while breastfeeding initiation rates approach
      Healthy People 2010 goals, breastfeeding duration remains far below these goals.
      Race/ethnicity differences in experiences related to breastfeeding cessation
      suggest that culturally sensitive breastfeeding interventions are necessary.

PMID- 18336644
TI  - Breast or bottle? Eating disordered childbearing women and infant-feeding
      decisions.
AB  - Debates about infant-feeding methods have intensified in recent years with
      increasing pressures on women living in industrialized nations to breastfeed
      their infants. This paper, based on a qualitative study of 16 childbearing women
      with a pre-existing eating disorder living in the north of England, examines
      participants' motivations for, and understandings of, infant-feeding decisions
      and practices. In this study, a small number of participants reported being
      'desperate' to formula feed in order to resume practices underpinning their
      eating disorder and thereby to shed the weight accumulated during pregnancy.
      These participants anticipated an early return to restrictive eating, heavy
      exercise regimes and/or bingeing/purging behaviours. Most participants, however,
      reported being 'desperate' to breastfeed because this implied 'good' mothering
      and prolonged the time during which they could consume 'naughty' treats. Women
      who opted to breastfeed generally believed this would accelerate weight loss.
      This study contributes to research on the subjective experiences of a particular
      group of women living with chronic illnesses and problematic relationships with
      their bodies. Negotiating individual transitions to motherhood required
      participants to confront their own, often longstanding, disrupted eating patterns
      and to make important decisions about infant-feeding methods. Findings from this
      study raise questions about some of the assumptions underpinning infant-feeding
      activities and articulate some of the complexities surrounding these issues. By
      highlighting ways in which women may compromise their own well-being by
      prioritizing their baby's needs, for example by persisting with breastfeeding
      when they were 'desperate' to re-engage with their disordered eating practices,
      an individualized cost-benefit framing is outlined.

PMID- 18336645
TI  - Social networks and infant feeding in Oaxaca, Mexico.
AB  - The health benefits of delaying the introduction of complementary foods to
      infants' diets are widely known. Many studies have shown that mothers with the
      support of close social network members are more compliant with medical
      recommendations for infant feeding. In our study, we examine the effects of a
      broader spectrum of network members (40 people) on mothers' infant feeding
      decisions. The survey was conducted in Oaxaca, Mexico as part of a follow-up to a
      nationwide Mexican Social Security Institute survey of infant health. Sixty
      mothers were interviewed from a stratified random sample of the original
      respondents. Multivariate tests were used to compare the efficacy of network
      level variables for predicting the introduction of 36 foods into infants' diets,
      when compared with respondent-level variables. The study yields four findings.
      First, network-level variables were better predictors of the timing of food
      introduction than socio-demographic variables. Second, mothers with more
      indigenous networks delayed the introduction of some grains (oatmeal, cereal,
      noodle soup, rice) and processed pork products (sausage and ham) to the infant's
      diet longer than mothers with less indigenous networks. Third, mothers who had
      stronger ties to their networks delayed the introduction of rice and processed
      pork products (sausage and ham) to the infant's diet longer than mothers who had
      weaker ties to their networks. Fourth, mothers who heeded the advice of distant
      network members introduced some grains (rice and cereal) earlier than mothers who
      did not heed the advice of distant network members.

PMID- 18336646
TI  - No difference indicated in electroencephalographic power spectral analysis in 3-
      and 6-month-old infants fed soy- or milk-based formula.
AB  - Increasing concern has been recently raised on the possible effects of soy
      derived phyto-oestrogens on the development of cognitive functions in infants.
      However, limited studies have been conducted to date, and no data have been made
      available for determining whether infant soy formula can affect normal
      development of the human brain. We compared electroencephalographic (EEG)
      spectral power derived from high-density recordings of infants fed milk-based or
      soy formula (46 fed milk-based formula and 39 fed soy formula) at 3 and 6 months
      of age. The spectral parameters included absolute power, relative power and
      spectral edge frequency (SEF) at 85%, 90% and 95% levels. The frequency domain
      contained four bands (0.1-3, 3-6, 6-9 and 9-12 Hz). EEG signals were collected
      from eight brain areas in each hemisphere. The results showed that the highest
      spectral power was mainly distributed in the low-frequency bands and was
      predominant in the frontal and anterior temporal areas. None of the spectral
      variables significantly differed between the soy- and milk-fed infants (anova,
      all P > 0.2). However, significant effects were indicated on the SEFs for factors
      of sex, age and brain area (all P < 0.01). Hemispheric differences in the
      absolute and relative power were also indicated. Our results suggest that the EEG
      power spectral development of soy-fed infants does not differ from that of
      infants fed milk-based formula. In addition, EEG spectral development appears
      more advanced in female than in male infants at 6 months.

PMID- 18336647
TI  - Intakes from non-breastmilk foods for stunted toddlers living in poor urban
      villages of Phnom Penh, Cambodia, are inadequate.
AB  - In Cambodia, the energy and nutrient densities of the traditional rice-based
      complementary diets used for infant feeding are very low. Whether the adequacy
      improves after the first year of life is uncertain. Therefore, we examined the
      feeding practices and the energy and nutrient intakes from non-breastmilk foods
      (NBMFs) of two groups: partially breastfed (PBF) (n = 41) and non-breastfed (NBF)
      (n = 210) stunted toddlers aged 12-42 months from poor villages in Phnom Penh,
      Cambodia. Intakes of NBMFs were estimated from 24-h recalls and a specially
      constructed Cambodian food composition table. All the toddlers were breastfed
      initially, but more than 50% received complementary foods before 6 months of age
      (mainly rice porridge). Many PBF toddlers received mixed feeding and were often
      bottle-fed diluted sweetened condensed milk. Unresponsive feeding was widespread.
      Inappropriate snacks, such as crisps, were the major source of energy, calcium,
      iron, zinc and vitamin A from NBMFs for the PBF group, and energy and iron for
      the NBF group. The snacks were often purchased and consumed without any adult
      supervision. For both groups, intakes of energy, calcium, iron and zinc were
      consistently below recommendations, as a result of the low micronutrient density
      of NBMFs and the small amounts fed per feeding. Increasing intakes of animal
      source foods and dark-green and yellow fruits and vegetables would enhance
      micronutrient densities, although this may be neither feasible nor sufficient to
      overcome the existing deficits. Instead, the feasibility of micronutrient
      fortification of the rice-based diets of Cambodian toddlers should be explored.

PMID- 18336650
TI  - 2nd International Symposium on Alcoholic Liver and Pancreatic Diseases and
      Cirrhosis, 18-19 October 2007, Kobe, Japan. Preface.

PMID- 18336651
TI  - Fat paradox of steatohepatitis.
AB  - Alcoholic and non-alcoholic steatohepatitis (ASH and NASH) constitute two major
      types of chronic liver disease with worldwide prevalence and are histologically
      indistinguishable with shared pathogenetic mechanisms. More importantly, they
      have synergistic interactions for liver pathology. Comparative studies on ASH and
      NASH have been hampered by the use of different animal models with confounding
      variables, particularly those with extreme genetic, toxic, and malnutrition
      etiologies. The mouse intragastric model circumvents these problems and
      reproduces the natural course and etiological background of ASH and NASH.
      Further, our recent work reproduces a profound synergism between the two in the
      model. Intracellular accumulation of neural lipids is a hallmark biochemical
      feature of ASH and NASH. Although impaired lipid oxidation and export may
      contribute to this pathological change, enhanced lipogenic regulation is
      frequently encountered, as characterized by induction of lipogenic or adipogenic
      transcription factors (peroxisome proliferator-activated receptor [PPAR gamma],
      liver X receptor alpha[LXR alpha], sterol-regulatory element-binding protein-1c
      [SREBP-1c]). In contrast, we have recently defined transdifferentiation of
      hepatic stellate cells (HSC), a pivotal event in liver fibrogenesis, as an
      'antilipogenic' or 'anti-adipogenic' phenomenon. Thus, there is an apparent
      paradox between hepatocytes and HSC in steatohepatitis in terms of the outcome of
      lipogenic regulation. Our recent work suggests that defective insulin signaling
      in activated HSC may be responsible for this paradox. Further, activated Wnt
      signaling is implicated in 'anti-adipogenic' stellate cell transdifferentiation
      in liver fibrogenesis.

PMID- 18336652
TI  - Epigenetic regulation of hepatic stellate cell activation.
AB  - Activation of hepatic stellate cells (HSC) to a myofibroblast-like phenotype is
      the pivotal event in liver fibrosis. In uninjured liver, HSC are quiescent and
      non-dividing, but upon liver injury these cells undergo a dramatic change in
      phenotype which generates activated myofibroblast-like HSC. The change in
      phenotype is underpinned by a global change in gene expression with hundreds of
      genes being up- or downregulated. Molecular events that orchestrate changes in
      gene expression take place at the level of chromatin packaging which is altered
      through three main processes: histone modifications, DNA methylation, and
      silencing by non-coding RNAs. The present review focuses on the epigenetic
      regulation of HSC activation.

PMID- 18336654
TI  - Pancreatic stellate cells: molecular mechanism of pancreatic fibrosis.
AB  - Pancreatic stellate cells (PSC) are known to play a crucial role in pancreatic
      fibrogenesis in chronic pancreatitis and in the desmoplastic reaction of
      pancreatic cancer. When PSC are stimulated by oxidative stress, the phenotype of
      quiescent fat-storing cells converts to myofibroblast-like activated PSC that
      then produce extracellular matrix (ECM), adhesion molecules, and various
      chemokines in response to inflammatory cytokines, chemokines, and growth factors.
      Platelet-derived growth factor (PDGF) is a potent stimulator of PSC
      proliferation, and transforming growth factor-beta, PDGF, and basic fibroblast
      growth factor stimulate ECM synthesis by PSC. As induction of acinar cell
      apoptosis and necrosis is a major mechanism in the pathogenesis of mild to severe
      acute pancreatitis, the rapid removal of apoptotic acinar cells may be helpful in
      preventing the release of toxic intracellular materials, preventing further
      progression of the inflammation, and restoring normal tissue homeostasis.
      Although PSC are not professional phagocytes, we have demonstrated that PSC
      engulf apoptotic polymorphonuclear neutrophils (PMN) and necrotic acinar cells.
      Apoptotic PMN are ingested into the cytoplasm of the PSC, and troglitazone
      induces a dose-dependent increase in both phagocytic activity and expression of
      CD36, which is a representative scavenger receptor for phagocytic function.
      Engulfment of necrotic acinar cells by PSC induced PSC death and inhibited PSC
      activation in an in vitro study, suggesting that engulfment of necrotic acinar
      cells by PSC may inhibit the progression of fibrogenesis. These findings suggest
      that engulfment of damaged cells by PSC may be one of the mechanisms that prevent
      the progression of pancreatitis and restore tissue homeostasis.

PMID- 18336653
TI  - Innate immunity and alcoholic liver fibrosis.
AB  - The hepatic innate immune system consists of predominant innate immunity, which
      plays an important role in innate defense against infection and tumor
      transformation. Emerging evidence suggests that innate immunity also contributes
      to liver injury, repair, and fibrosis. The present review summarizes the recent
      findings on the role of innate immunity in liver fibrosis. In general, Kupffer
      cells stimulate liver fibrosis via production of reactive oxygen species and pro
      inflammatory cytokines, whereas natural killer (NK) cells inhibit liver fibrosis
      by directly killing activated hepatic stellate cells and production of gamma
      interferon (IFN-gamma). Complement components, interferons, and Toll-like
      receptors have also been shown to regulate liver fibrosis. Recent evidence also
      suggests that modulation of innate immunity by alcohol plays an important role in
      the pathogenesis of alcoholic liver fibrosis. These include alcohol amplification
      of the profibrotic effects of Kupffer cells and suppression of the antifibrotic
      effects of NK/IFN-gamma.

PMID- 18336655
TI  - Transforming growth factor-beta and hepatocyte transdifferentiation in liver
      fibrogenesis.
AB  - Currently, hepatic stellate cells (HSC) are thought to be the major fibrotic
      precursor cells that transdifferentiate to fibrogenic, extracellular matrix
      producing myofibroblasts in inflammatory liver tissue upon transforming growth
      factor-beta (TGF-beta) signaling, whereas hepatocytes are thought to respond with
      apoptosis to this cytokine. Starting out from in vitro experiments with primary
      hepatocyte cultures and immortalized AML-12 cells, TGF-beta signaling in this
      cell type was assessed and apoptosis was found to be only a minor effect.
      Instead, hepatocytes undergo epithelial mesenchymal transition (EMT), a
      physiological process in embryogenesis and of relevance for cancerous cell
      transformation. In injured liver, however, this process contributes to the
      promotion of fibrosis. Already after a few days of culture, hepatocytes lose
      their epithelial honeycomb-like shape towards a fibroblast-like phenotype. We
      could demonstrate by microarray analysis that stimulation of hepatocytes with TGF
      beta regulates the expression of genes involved in EMT and fibrosis. Among these
      were, for example, Snail, a known mediator of EMT, and connective tissue growth
      factor (CTGF), a strong inducer of fibrosis. In a mouse model, hepatocyte
      specific overexpression of Smad7 was able to blunt a fibrogenic response after
      CCl(4) intoxication. These results emphasize the dynamic nature of liver
      fibrosis, challenge the paradigm of HSC as a crucial source of liver
      myofibroblasts and hint towards a prominent role for hepatocytes in liver
      fibrogenesis.

PMID- 18336656
TI  - French National Research Program on alcohol.

PMID- 18336657
TI  - Dissection of endoplasmic reticulum stress signaling in alcoholic and non
      alcoholic liver injury.
AB  - Accumulation of unfolded or malfolded proteins induces endoplasmic reticulum (ER)
      stress which elicits a complex network of interacting and parallel responses that
      dampen the stress. The ER stress response in the liver is controlled by intrinsic
      feedback effectors and is initially protective. However, delayed or insufficient
      responses or interplay with mitochondrial dysfunction may turn physiological
      mechanisms into pathological consequences including apoptosis, fat accumulation
      and inflammation all of which have an important role in the pathogenesis of liver
      disorders such as genetic mutations, viral hepatitis, insulin resistance,
      ischemia/reperfusion injury, and alcoholic and non-alcoholic steatosis. In both
      alcohol and non-alcohol-induced ER stress, a common candidate is
      hyperhomocysteinemia. Betaine supplementation and/or expression of betaine
      homocysteine methyltransferase (BHMT) promote removal of homocysteine and
      alleviate ER stress, fatty accumulation and apoptosis in cultured hepatocytes and
      mouse models. The rapidity and magnitude of homocysteine-induced activation of
      each of the main ER resident transmembrane sensors including inositol requiring
      enzyme 1 (IRE-l alpha), activating transcription factor 6 (ATF-6) and RNA
      activated protein kinase (PKR)-like ER kinase (PERK) appear different in
      different experimental models. Dissection and differentiation of ER stress
      signaling may reveal clues on the specific importance of the ER stress response
      in contributing to liver injury and thus provide better strategies on prevention
      and treatment of liver disease.

PMID- 18336658
TI  - Quantifying the risk for alcohol-use and alcohol-attributable health disorders:
      present findings and future research needs.
AB  - The aim of the present review was to: (i) highlight epidemiological and other
      studies that have generated important data on the harmful patterns of drinking
      that increase the risk for chronic diseases, including alcohol dependence, and on
      the mechanisms by which alcohol produces and, in some instances, may protect
      against damage; and (ii) discuss a conceptual basis for quantifying risk criteria
      for alcohol-induced chronic disease based on the quantity, frequency, and pattern
      of drinking. The relationship between heavy drinking and risk for adverse health
      conditions such as alcoholic liver disease (ALD), dementia, and alcohol
      dependence is well known. However, not everyone who drinks chronically develops
      ALD or dementia, and the major risk factors for disease development and the
      mechanisms by which this occurs have remained unclear. Large-scale, general
      population-based studies have provided the evidence by which quantifying the
      frequency of a pattern of high-risk drinking can be related directly to risk and
      the severity of alcohol dependence. Cellular and molecular biology studies have
      identified the major pathways of alcohol metabolism and how genetics and the
      environment can interact in some individuals to further increase the risk of
      organ damage. Extant databases should allow scientists and clinicians jointly to
      develop the framework for quantifying the drinking patterns that increase the
      risk of alcohol-induced organ pathologies, to develop clinical practice
      guidelines, such as those used to diagnose other common complex diseases (e.g.
      diabetes and hypertension), and to propose future studies for refining such
      guidelines. Attention must be paid to comorbid conditions such as hepatitis B and
      C infections, HIV, obesity, and environmental exposures other than alcohol.
      Developing trait and state biomarkers is critical to the process of discovery and
      to fulfilling the promise of personalized medicine.

PMID- 18336659
TI  - Mitochondrial mechanisms of death responses in pancreatitis.
AB  - Pancreatitis is a severe and frequently lethal disorder, a major cause of which
      is alcohol abuse. Parenchymal cell death is a major complication of pancreatitis.
      In experimental models of acute pancreatitis, acinar cells have been shown to die
      through both necrosis and apoptosis, the two principal pathways of cell death.
      The severity of experimental acute pancreatitis correlates directly with the
      extent of necrosis and inversely with apoptosis. Thus, understanding the
      regulation of apoptosis and necrosis is becoming exceedingly important in
      investigations of the pathogenesis and treatment of pancreatitis. Over the past
      decade, the mitochondria have emerged as a master regulator of cell death in
      various physiological and pathological processes. Release of mitochondrial
      cytochrome c into the cytosol is a central event in apoptosis, whereas
      mitochondrial depolarization resulting in ATP depletion leads to necrosis. The
      present review focuses on the mitochondrial mechanisms of death responses in
      pancreatitis, with emphasis on mitochondrial membrane permeabilization and its
      role in the balance between apoptosis and necrosis in acute pancreatitis, and
      alcohol's effects on death responses of pancreatitis.

PMID- 18336660
TI  - Ca2+-induced pancreatic cell death: roles of the endoplasmic reticulum, zymogen
      granules, lysosomes and endosomes.
AB  - Alcohol induces Ca(2+)-dependent intracellular trypsinogen activation in the
      apical granular area via non-oxidative metabolites, such as fatty acid ethyl
      esters and fatty acids. Intracellular trypsinogen activation is a crucial
      initiating event in the development of acute pancreatitis, but the specific
      organelle in which this process takes place has been unknown. Recent data
      demonstrate that the Ca(2+)-dependent trypsinogen activation occurs in
      postexocytotic endocytic vacuoles. These vacuoles are acid due to a bafilomycin
      sensitive vacuolar H(+) ATPase and have a very Ca(2+)-permeable membrane. Acid
      endocytic structures, together with lysosomes, zymogen granules and elements of
      the endoplasmic reticulum, also play an important role in the physiological
      Ca(2+) signal generation that normally regulates enzyme and fluid secretion from
      the exocrine pancreas.

PMID- 18336661
TI  - Protein kinase C in the pancreatic acinar cell.
AB  - Pathological activation of selective signaling molecules within the pancreatic
      acinar cell mediates the development of acute pancreatitis. Some of the key early
      acinar cell events include activation of proteases, inhibition of apical
      secretion, and elaboration of inflammatory mediators. Previous studies have shown
      that supraphysiological concentrations of cholecystokinin (CCK) that can cause
      pancreatitis in vivo, also initiate these pathological responses in dispersed
      groups of acinar cells (acini). Protein kinase C (PKC) regulates many cellular
      events and a role for this family of signaling molecules has been described in
      some of the pathological responses of pancreatitis. Notably, ethanol can activate
      specific PKC isoforms and sensitize the acinar cells to the pathological effects
      of CCK. Our preliminary studies in isolated pancreatic acini and a cell-free
      reconstitution system suggest that PKC can mediate protease activation in the
      acinar cell. These findings may be relevant to the pathogenesis of pancreatitis
      from alcohol and other etiologies.

PMID- 18336662
TI  - Heat shock proteins in pancreatic diseases.
AB  - Heat shock proteins (HSPs) are chaperone proteins that protect living cells
      against injury-inducing stimuli. Dysregulated expression of HSPs has been
      observed in various disease conditions including cancer. Using knock-out and
      transgenic animal approach, as well as standard, methods of heat shock protein 70
      (HSP70) induction (i.e. thermal stress and arsenite administration), it has been
      shown that HSP70 protects against cell injury and acinar necrosis in experimental
      model of pancreatitis in animals. Animals in which HSP70 is induced prior to
      cerulein administration in a cerulein model of pancreatitis have reduced severity
      of pancreatitis, as demonstrated by lower serum amylase, lesser acinar necrosis
      on histology and decreased neutrophilic infiltration, suggesting that HSP70 is
      protective against cell death. Similar to the protective role of HSP70 in a
      pancreatitis model, HSP70 overexpression has been observed in pancreatic cancer
      and is believed to protect cancer cells from cell death. HSP70 is overexpressed
      both at mRNA and protein levels in pancreatic cancer cell lines as compared to
      normal pancreatic ductal cells. On a more clinical note, HSP70 is present in
      great abundance in pancreatic cancer clinical specimens as compared to normal
      pancreatic margins. Inhibition of HSP70 expression in pancreatic cancer cells
      leads to caspase-dependent apoptotic cell death and is a novel therapeutic
      modality for pancreatic cancer. Triptolide is a pharmacological agent which
      highly effective inhibiting HSP70 expression in pancreatic cancer cells and thus
      induces cell death. Moreover, triptolide is highly efficacious in reducing growth
      as well as locoregional spread of pancreatic tumors in an orthotopic model of
      pancreatic cancer and has tremendous potential as a novel therapeutic agent.

PMID- 18336663
TI  - Impaired receptor-mediated endocytosis: its role in alcohol-induced apoptosis.
AB  - Hepatocyte apoptosis, inflammation, and fibrosis are prominent features of liver
      disease in general and of alcoholic liver injury in particular. Although the link
      between these processes remains unclear, one universal characteristic of liver
      injury is the induction of hepatocellular damage, which results in the generation
      of apoptotic bodies. Work from our laboratory over the last several years has
      studied the effect of ethanol administration on the process of apoptosis and a
      role for altered endocytosis in alcoholic apoptosis. We initially focused our
      research on the hepatocyte by examining endocytosis using the asialoglycoprotein
      receptor (ASGP-R) pathway as a model and we identified multiple ethanol-induced
      impairments in receptor function. We also showed that uptake of apoptotic bodies
      is impaired in hepatocytes isolated from ethanol-fed animals compared to
      controls, and that this impairment is linked to altered ASGP-R function. Recent
      work from our laboratory is examining a link between ethanol-impaired ASGP-R
      function, apoptotic body accumulation, and inflammation in the liver. We are
      particularly interested in data showing that factors produced by Kupffer cells
      incubated with apoptotic bodies can lead to production of tumor necrosis factor
      alpha and interleukin-6, and that this effect is exacerbated in the setting of
      alcohol administration. In addition, we have preliminary data showing that media
      from Kupffer cell cultures incubated with apoptotic bodies can induce hepatocyte
      killing. The goal of our future work is to show that inadequate removal of
      apoptotic cells, in part via altered receptor-mediated endocytosis, plays a role
      in the course of pathogenesis of alcoholic liver injury.

PMID- 18336664
TI  - Mechanisms for the anti-inflammatory effects of adiponectin in macrophages.
AB  - Adiponectin is an adipokine with potent anti-inflammatory properties. The
      development of alcoholic liver disease is thought to involve increased pro
      inflammatory activity, mediated in part by the activation of hepatic macrophages
      (Kupffer cells). Chronic ethanol feeding sensitizes hepatic macrophages to
      activation by lipopolysaccharide (LPS), leading to increased production of
      reactive oxygen species and tumor necrosis factor-alpha (TNF-alpha). Adiponectin
      can normalize Toll-like receptor-4 (TLR-4) mediated signaling in hepatic
      macrophages after ethanol feeding, likely contributing to the hepatoprotective
      effect of adiponectin in the progression of alcoholic liver disease. However, the
      mechanisms by which adiponectin suppress TLR-4 mediated responses are not well
      understood. Using the macrophage-like cell line, RAW264.7, we have investigated
      the molecular mechanisms by which adiponectin suppresses LPS-stimulated TNF-alpha
      production. Globular adiponectin (gAcrp)-mediated desensitization of LPS
      stimulated responses in RAW264.7 macrophages was dependent on the production of
      the anti-inflammatory cytokine interleukin (IL)-10. gAcrp initially increased TNF
      alpha expression in RAW264.7 macrophages; this TNF-alpha then contributed to
      increased expression of IL-10. This initial gAcrp-mediated increase in TNF-alpha
      production by macrophages was mediated via activation of ERK1/2-->Egr-1 and
      nuclear factor (NF)-kappaB-dependent mechanisms. gAcrp-stimulated IL-10
      expression was also dependent on the phosphorylation of cAMP response element
      binding protein and the cAMP response element in the IL-10 promoter. In summary,
      these studies reveal a complex, integrated response of macrophages to gAcrp.
      gAcrp initially activated signaling pathways considered to be pro-inflammatory,
      with a subsequent increase in the expression of the potent, anti-inflammatory
      cytokine, IL-10. Increased IL-10 expression was ultimately required for the
      suppression of TLR4-mediated signaling by gAcrp.

PMID- 18336665
TI  - New role of plasminogen activator inhibitor-1 in alcohol-induced liver injury.
AB  - Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen
      activators, thereby playing a major role in fibrinolysis. Whereas
      hyperfibrinolysis is common in alcoholic cirrhosis, hypofibrinolysis (driven
      mostly by elevated levels of PAI-1) is common during the development of alcoholic
      liver disease (ALD). However, whether or not PAI-1 plays a causal role in the
      development of ALD has been unclear. The role of PAI-1 was therefore investigated
      in models of early (steatosis), intermediate (inflammation/necrosis) and late
      (fibrosis) stages of alcoholic liver disease. For example, hepatic steatosis
      caused by both acute and chronic ethanol was blunted by inhibiting PAI-1
      activation. This effect of inhibiting PAI-1 appears to be mediated, at least in
      part, by an increase in very low-density lipoprotein (VLDL) synthesis in the
      absence of PAI-1. The results from that study also indicated that PAI-1 plays a
      critical role in both acute and chronic hepatic inflammation. Lastly, knocking
      out PAI-1 potently protected against experimental hepatic fibrosis; the mechanism
      of this protective effect appears to be mediated predominantly by extracellular
      matrix (ECM) resolution by matrix metalloproteases, which are indirectly
      inhibited by PAI-1. In summary, targeting PAI-1 protects against all three stages
      of ALD in model systems. The mechanisms by which PAI-1 contributes to these
      disease stages appear to not only involve the 'classical' function of PAI-1 (i.e.
      in mediating fibrinolysis), but also other functions of this protein. These data
      support a role of PAI-1 in the initiation and progression of ALD, and suggest
      that PAI-1 may be a useful target for clinical therapy to halt or blunt disease
      progression.

PMID- 18336666
TI  - Treatment of severe forms of alcoholic hepatitis: where are we going?
AB  - Alcoholic hepatitis (AH) is observed in approximately 20% of heavy drinkers. The
      treatment of AH remains one of the main challenges to clinicians involved in the
      management of severe alcoholic liver disease. Corticosteroids improved the short
      term survival of patients with severe AH. Nevertheless, the efficacy of
      corticosteroids is still considered controversial for some authors.
      Pentoxifylline may be considered an alternative to corticosteroids. Early
      identification of subjects with substantial risk of death according to the Lille
      model will improve management of patients suffering from severe AH and will aid
      in the design of future studies for alternative therapies. Alternative therapies
      are required to improve the prognosis of patients with a severe form of AH.
      Progress in understanding the pathogenesis of AH is opening up an exciting new
      era and is lending impetus to future evaluation of new drugs targeting the tumor
      necrosis factor pathways.

PMID- 18336667
TI  - Individual susceptibility to alcoholic pancreatitis.
AB  - The observation that only a minority of heavy drinkers develop pancreatitis has
      prompted an intensive search for a trigger factor/cofactor/susceptibility factor
      that may precipitate a clinical attack. Putative susceptibility factors examined
      so far include diet, smoking, amount and type of alcohol consumed, the pattern of
      drinking and lipid intolerance. In addition, a range of inherited factors have
      been assessed including blood group antigens, human leukocyte antigen serotypes,
      alpha-1-antitrypsin phenotypes and several genotypes. The latter group comprises
      mutations/polymorphisms in genes related to alcohol-metabolizing enzymes,
      detoxifying enzymes, pancreatic digestive enzymes, pancreatic enzyme inhibitors,
      cystic fibrosis and cytokines. Disappointingly, despite this concerted research
      effort, no clear association has been established between the above factors and
      alcoholic pancreatitis. Experimentally, the secretagogue cholecystokinin (CCK)
      has been investigated as a candidate 'trigger' for alcoholic pancreatitis.
      However, the clinical relevance of CCK as a trigger factor has to be questioned,
      as it is difficult to envisage a situation in humans where abnormally high levels
      of CCK would be released into the circulation to trigger pancreatitis in
      alcoholics. In contrast, bacterial endotoxemia is a candidate cofactor that does
      have relevance to the clinical situation. Plasma lipopolysaccharide (LPS, an
      endotoxin) levels are significantly higher in drinkers (either after chronic
      alcohol intake or a single binge) compared to non-drinkers. We have recently
      shown that alcohol-fed animals challenged with otherwise innocuous doses of LPS
      exhibit significant pancreatic injury. Moreover, repeated LPS exposure in alcohol
      fed rats leads to progressive injury to the gland characterized by significant
      pancreatic fibrosis. These studies support the concept that endotoxin may be an
      important factor in the initiation and progression of alcoholic pancreatitis.
      Scope remains for further studies examining proteins related to cellular anti
      oxidant defenses, minor cystic fibrosis (CF) mutations and trans-heterozygosity
      involving a combination of mutations of different genes (such as CFTR alterations
      combined with SPINK1 or PRSS1 variants), as potential triggers of alcoholic
      pancreatitis.

PMID- 18336668
TI  - Association analysis among polymorphisms of the various genes and chronic
      alcoholic pancreatitis.
AB  - Chronic and excessive consumption of alcohol is an important factor responsible
      for the onset of pancreatitis. However, the incidence of chronic pancreatitis in
      heavy drinkers differs in individuals, suggesting that these individual
      differences may involve various genetic and environmental factors. In the present
      study, we investigated an association of alcoholic pancreatitis with
      polymorphisms of the various genes related to metabolism of the oxidative
      compounds. We analyzed polymorphisms of NADPH-quinone oxidoreductase 2 (NQO2),
      multidrug resistance 1 (MDR1), alcohol dehydrogenase 1B (ADH1B) and lipoprotein
      lipase (LPL). The subjects consisted of 53 patients with chronic alcoholic
      pancreatitis (AlCP), 54 alcoholic patients without pancreatic dysfunction (Alc),
      and 42 healthy individuals. DNA samples were prepared from the peripheral blood
      of all subjects, and the genetic mutations were analyzed by polymerase chain
      reaction and restriction fragment length polymorphism methods. The ADH1B gene
      frequencies were significantly different between healthy controls and Alc
      patients (P < 0.001), and also between AlCP and Alc patients (P < 0.05). However,
      no significant difference was found between healthy controls and AlCP patients.
      The gene frequencies of MDR1 (3435C > T) and MDR1 (2677G > A/T) of patients with
      AlCP or Alc were different when compared with healthy controls, although the
      difference was not significant. The NQO2 and LPL genes showed no relation with
      Alc and AlCP patients. The ADH1B*1 gene frequency in AlCP was significantly lower
      compared with Alc. We speculate that the ADH1B*1 gene may function by reducing
      vulnerability to the onset of alcoholic pancreatitis. Other genes analyzed in the
      present study lacked association with AlCP.

PMID- 18336669
TI  - S-Adenosylmethionine in cell growth, apoptosis and liver cancer.
AB  - S-Adenosylmethionine (SAMe), the principal biological methyl donor, is
      synthesized from methionine and ATP in a reaction catalyzed by methionine
      adenosyltransferase (MAT). In mammals, two genes (MAT1A and MAT2A), encode for
      two homologous MAT catalytic subunits, while a third gene MAT2beta, encodes for
      the beta-subunit that regulates MAT2A-encoded isoenzyme. Normal liver expresses
      MAT1A, whereas extrahepatic tissues express MAT2A. MAT2A and MAT2 beta are
      induced in human hepatocellular carcinoma (HCC), which facilitate cancer cell
      growth. Patients with cirrhosis of various etiologies, including alcohol, have
      decreased hepatic MAT activity and SAMe biosynthesis. Consequences of hepatic
      SAMe deficiency as illustrated by the Mat1a knock-out mouse model include
      increased susceptibility to steatosis and oxidative liver injury, spontaneous
      development of steatohepatitis and HCC. Predisposition to HCC can be partly
      explained by the effect of SAMe on growth. Thus, SAMe inhibits the mitogenic
      effect of growth factors such as hepatocyte growth factor and, following partial
      hepatectomy, a fall in SAMe level is required for the liver to regenerate. During
      liver regeneration, the fall in hepatic SAMe is transient. If the fall were to
      persist, it would favor a proliferative phenotype and, ultimately, development of
      HCC. Not only does SAMe control liver growth, it also regulates apoptosis.
      Interestingly, SAMe is anti-apoptotic in normal hepatocytes but pro-apoptotic in
      liver cancer cells. In liver cancer cells but not in normal human hepatocytes,
      SAMe can selectively induce Bcl-x(S), an alternatively spliced isoform of Bcl
      x(L) that promotes apoptosis. This should make SAMe an attractive agent for both
      chemoprevention and treatment of HCC.

PMID- 18336670
TI  - Dysregulation of systemic iron metabolism in alcoholic liver diseases.
AB  - Alcoholic liver diseases (ALD) are frequently associated with iron overload.
      Until recently, the effects of ethanol in hepatic iron uptake and intestinal iron
      absorption have not been clarified in detail. Two possible mechanisms for iron
      overload are the uptake of iron into hepatocytes in a specific manner through the
      increased expression of transferrin receptor (TfR) 1; and increased intestinal
      iron absorption by the lowering of hepcidin. It is worthwhile to examine whether
      a similar mechanism is present in the development of steatosis and non-alcoholic
      steatohepatitis (NASH). Hepatocytes have several iron uptake pathways. Ethanol
      increases transferrin (Tf)-mediated uptake via a receptor-dependent manner, but
      downregulates the non-Tf-bound iron uptake. According to immunohistochemical
      study, TfR1 was increased in hepatocytes in 80% of hepatic tissues of patients
      with ALD, but was not detected in normal hepatic tissues. In an experimental
      model, ethanol exposure to the primary cultured-hepatocytes in the presence of
      iron increased TfR1 expression and (59)Fe-labeled Tf uptake. In patients with
      ALD, intestinal iron absorption is increased by oral iron uptake assay. The
      regulatory hormone for iron homeostasis, hepcidin is downregulated in ethanol
      loaded mice liver. As well as ALD, a similar mechanism was present in the mouse
      model fed with a high-fat diet, a model of the initial phenomenon of steatosis.
      The common mechanism for hepatic iron deposition and the triggering role of iron
      may be present in the development of ALD and non-alcoholic fatty liver
      disease/NASH.

PMID- 18336671
TI  - SPINK1, ADH2, and ALDH2 gene variants and alcoholic chronic pancreatitis in
      Japan.
AB  - The serine protease inhibitor Kazal type 1 (SPINK1) is a potent antiprotease and
      an important inactivation factor of intrapancreatic trypsin activity. Loss of
      function by the SPINK1 mutations leads to decreased inhibitory capacity. The
      significance of SPINK1 mutations in alcoholic chronic pancreatitis (CP) in Japan
      and its functional role remain unclear. The aim of the present study was to
      clarify the incidence of SPINK1, alcohol dehydrogenase 2 (ADH2) and aldehyde
      dehydrogenase 2 (ALDH2) variants in CP patients in Japan. One hundred and 86
      patients with CP, and 527 healthy volunteers were enrolled. Mutational analyses
      were performed by polymerase chain reaction-restriction fragment length
      polymorphism and direct sequencing. Serum pancreatic secretory trypsin inhibitor
      (PSTI) level was measured by radioimmunoassay. The frequencies of N34S and IVS3 +
      2T > C in the SPINK1 gene were significantly higher in patients with non
      alcoholic CP (12.9% and 8.6%, respectively) than in normal subjects (0.37% and
      0%). In total, 18 of 93 (19.4%) patients with non-alcoholic CP had at least one
      SPINK1 mutation. Concerning alcoholic CP, we found IVS3 + 2T > C in a small
      number of patients (3.9%). Serum PSTI concentration was decreased in patients
      with the IVS3 + 2T > C mutation. The frequency of the ADH2*2 allele in the
      alcoholic CP group was significantly higher than that in alcoholics without
      pancreatitis. The frequency of the ALDH2*2 allele was significantly low in
      patients with alcoholic CP compared with healthy controls. In conclusion, SPINK1
      mutations were associated with non-alcoholic CP. Furthermore, we revealed the
      amount of wild-type PSTI was decreased in patients with IVS3 + 2T > C mutation.
      Variants of alcohol-metabolizing enzymes appeared in the relation to alcoholic
      CP.

PMID- 18336672
TI  - Molecular basis for the synergy between alcohol and hepatitis C virus in
      hepatocarcinogenesis.
AB  - Overwhelming lines of epidemiological evidence have indicated that persistent
      infection with hepatitis C virus (HCV) is a major risk for the development of
      hepatocellular carcinoma (HCC). In addition, heavy alcohol use has been linked
      with earlier progression to HCC in chronic hepatitis C patients. However, in the
      pathogenesis of HCV-associated HCC, it still remains controversial as to whether
      the virus plays a direct or an indirect role, and as to how alcohol operates in
      the acceleration of HCC development. Several studies using transgenic mouse
      models, in which the core protein of HCV has an oncogenic potential, indicate
      that HCV is directly involved in hepatocarcinogenesis, although other factors
      such as continuous inflammation or environmental factors seem also to play a
      role. The downstream events of the HCV core protein expression in the transgenic
      mouse HCC model are segregated into two pathways. One is the augmented production
      of oxidative stress in the absence of inflammation along with the attenuation of
      some scavenging systems in the putative preneoplastic stage with steatosis in the
      liver. The other pathway is the alteration in cellular gene expression and
      intracellular signaling, including the mitogen-activated protein kinase cascade.
      The combination of these pathways would explain the unusually high incidence and
      multicentric nature of HCC development in HCV infection. In addition, alcohol
      feeding in this animal model further activated the two pathways synergistically
      with HCV, leading to an earlier development of HCC. Such a synergy would reveal
      the molecular basis for the acceleration of HCC development by alcohol in HCV
      infection.

PMID- 18336673
TI  - Cholesterol and sphingolipids in alcohol-induced liver injury.
AB  - The pathogenesis of alcohol-induced liver disease (ALD) is still poorly
      understood. One of the clues to its progression relates to the alcohol-mediated
      susceptibility of hepatocytes to cell death by reactive oxygen species (ROS) and
      inflammatory cytokines. Tumor necrosis factor alpha (TNF) has been considered a
      key ALD mediator with acidic sphingomyelinase (ASMase)-mediated ceramide
      generation playing a critical role. TNF receptor 1 and 2 knock-out mice or
      ASMase(-/-) mice exhibit resistance to alcohol-mediated fatty liver and cell
      death. Furthermore, alcohol feeding has been shown to sensitize hepatocytes to
      TNF due to the limitation of mitochondrial glutathione (mGSH) through impaired
      import of GSH from the cytosol due to altered membrane order parameter caused by
      mitochondrial cholesterol increase. Selective pharmacological depletion of mGSH
      sensitizes hepatocytes to TNF-mediated cell death, which reproduces the
      observations found with alcohol feeding. TNF signaling analyses in hepatocytes
      with or without mGSH depletion indicate that mGSH prevents cardiolipin
      peroxidation (CLOOH) formation by TNF-induced ROS via ASMase and that CLOOH
      cooperates with oligomerized Bax to cause mitochondrial outer membrane
      permeabilization through destabilization of the lipid bilayer via increased
      bilayer-to-inverted hexagonal phase transitions. Thus, activation of ASMase and
      cholesterol-mediated mGSH depletion both collaborate to promote alcohol-induced
      TNF-mediated hepatocellular damage, suggesting novel therapeutic opportunities in
      ALD.

PMID- 18336674
TI  - Alcohol, cofactors and the genetics of hepatocellular carcinoma.
AB  - Heavy alcohol consumption, chronic infection with the hepatitis B virus (HBV) or
      the hepatitis C virus (HCV), tobacco smoking, and diabetes are risk factors for
      hepatocellular carcinoma (HCC). In the Los Angeles Non-Asian HCC Study, heavy
      alcohol intake was shown to exhibit synergistic effects with viral hepatitis
      (HBV, HCV) and diabetes in the causation of HCC among individuals with joint
      exposures. Although chronic infection with HBV is recognized as the most
      important causal factor for HCC in humans, only a minority of HBV carriers
      eventually develop HCC, suggesting the presence of important cofactors in HBV
      related HCC. In the Guangxi/China HCC Study, a 20-fold difference in HCC risk was
      observed between individuals possessing the least versus the most favorable
      cytokine genotypes for hepatitis B viral clearance. Experimental studies have
      indicated an important role for one-carbon metabolism in HCC development. In both
      the Los Angeles and Guangxi studies, low-activity genotypes (reduced enzymatic
      activities) of methylenetetrahydrofolate reductase (MTHFR) and high-activity
      genotypes (enhanced enzymatic activities) of thymidylate synthase (TYMS), both of
      which discourage the misincorporation of uracil into DNA, were shown to be
      associated with a reduced risk for HCC.

PMID- 18336675
TI  - Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex.
AB  - Alcohol is a well-known risk factor for liver damage and is one of the major
      causes of liver disease worldwide. Chronic intake of alcohol, over a certain
      limit, inevitably leads to hepatic steatosis. If the injury persists, steatosis
      with concomitant tumor necrosis factor-alpha and other cytokines, progresses to
      steatohepatitis, fibrosis and finally cirrhosis. Among the multiple factors
      involved in the process of alcohol-induced liver injury, a crucial role is played
      by oxidative stress. Several mechanisms during ethanol metabolism result in
      reactive oxygen species (ROS) production. Although the main site of ethanol
      metabolism is hepatocytes, other mechanisms are involved in alcohol-induced liver
      injury. Specifically, in the ROS production activity, an important role is played
      by the NADPH oxidase complex. NADPH oxidase is expressed in hepatocytes, hepatic
      stellate cells and Kupffer cells in the liver. Studying NADPH oxidase gives new
      insights into alcohol-induced liver damage and provides new direction for future
      therapeutic strategies.

PMID- 18336676
TI  - The impact of public or private schools on smoking prevalence among adolescents
      in 2 countries.

PMID- 18336677
TI  - School-based obesity interventions: a literature review.
AB  - BACKGROUND: Childhood obesity is an impending epidemic. This article is an
      overview of different interventions conducted in school settings so as to guide
      efforts for an effective management of obesity in children, thus minimizing the
      risk of adult obesity and related cardiovascular risk. METHODS: PubMed and OVID
      Medline databases were searched for school-based obesity interventions with
      anthropometric measures in children and adolescents between the ages of 7 and 19
      years from June 1986 to June 2006. Studies were reviewed by duration, type of
      intervention, and defined qualitative and quantitative measures, resulting in a
      yield of 51 intervention studies. RESULTS: The interventions ranged from 4 weeks
      in length to as long as 8 continuing years. In total, 15 of the intervention
      studies exclusively utilized physical activity programs, 16 studies exclusively
      utilized educational models and behavior modification strategies, and 20 studies
      utilized both. In addition, 31 studies utilized exclusively quantitative
      variables like body mass indices and waist-to-hip ratios to measure the efficacy
      of the intervention programs, and another 20 studies utilized a combination of
      quantitative and qualitative measures that included self-reported physical
      activity and attitude toward physical activity and the tested knowledge of
      nutrition, cardiovascular health, and physical fitness. A total of 40 studies
      achieved positive statistically significant results between the baseline and the
      follow-up quantitative measurements. CONCLUSIONS: No persistence of positive
      results in reducing obesity in school-age children has been observed. Studies
      employing long-term follow-up of quantitative and qualitative measurements of
      short-term interventions in particular are warranted.

PMID- 18336678
TI  - Biscuits, sausage, gravy, milk, and orange juice: school breakfast environment in
      4 rural Appalachian schools.
AB  - BACKGROUND: The purpose of this study was to assess the school breakfast
      environment in rural Appalachian schools to inform school environment
      intervention and policy change. METHODS: A total of 4 rural schools with fourth-
      and fifth-grade students in East Tennessee were assessed. A cross-sectional
      descriptive examination of the school food environment where food service
      managers submitted school menus, production sheets, and vendor bid sheets as part
      of the dietary data collection protocol for a school-based nutrition intervention
      study. The school breakfast environment was characterized in terms of calories,
      fat, saturated fat, and fiber from foods served on a per person basis using menus
      entered into Nutrient Data Systems for Research and production sheets for amounts
      of each food item served. Food items were grouped by the meal components of the
      School Breakfast Program (SBP) and ranked according to the items served most
      frequently. RESULTS: Total fat provided slightly less than half the calories
      (43%); 15% of calories were from saturated fat. The top-ranked foods for each
      meal component were biscuits, sausage, 2% milk, orange juice, and gravy.
      CONCLUSIONS: Results suggest that clearer policies or regulations for the SBP are
      warranted to support policy efforts to promote childhood health. These should
      include technical assistance and provision of resources for school food service
      managers to provide low-fat meal options. Further research is needed to determine
      whether what is offered at school breakfast is actually consumed and how that
      might affect children's weight because of the high fat content.

PMID- 18336679
TI  - Children's perceptions of parental attitude affecting breakfast skipping in
      primary sixth-grade students.
AB  - BACKGROUND: Breakfast skipping is an international public health concern. This
      study investigated the prevalence of breakfast skipping among primary sixth-grade
      students in Hong Kong and the impact of students' perceptions of parental
      attitudes on breakfast skipping. METHODS: A total of 426 students aged 10-14
      years in 4 local schools participated in this cross-sectional study and completed
      a questionnaire adapted from an earlier study in Queensland. Breakfast skipping
      was defined as having missed any food or beverage (except water) between waking
      and the commencement of morning school classes at least 1 school day during the
      past week. Multiple logistic regression analyses were performed to explore the
      potential risk factors of breakfast skipping. RESULTS: Of the 426 students, 130
      (30.5%, 95% confidence interval [CI]: 26.1-34.9) reported skipping breakfast for
      at least 1 day in a school week. Multiple logistic regression analyses showed
      that breakfast skipping was associated with lack of perceived parental emphasis
      on breakfast (odds ratio [OR] = 3.67, 95% CI: 1.75-7.68) and not believing that
      breakfast consumption could help concentration in class (OR = 3.82, 95% CI: 1.86
      7.87). CONCLUSIONS: This study suggested that breakfast consumption habits could
      stem from the students' beliefs and perceptions. Thus, working with students,
      parents, and schools to build up positive knowledge and beliefs about breakfast
      consumption might be useful.

PMID- 18336680
TI  - Diet quality and academic performance.
AB  - BACKGROUND: Although the effects of nutrition on health and school performance
      are often cited, few research studies have examined the effect of diet quality on
      the academic performance of children. This study examines the association between
      overall diet quality and academic performance. METHODS: In 2003, 5200 grade 5
      students in Nova Scotia, Canada, and their parents were surveyed as part of the
      Children's Lifestyle and School-performance Study. Information on dietary intake,
      height, and weight and sociodemographic variables were linked to results of a
      provincial standardized literacy assessment. Diet Quality Index-International was
      used to summarize overall diet quality. Multilevel regression methods were used
      to examine the association between indicators of diet quality and academic
      performance while adjusting for gender and socioeconomic characteristics of
      parents and residential neighborhoods. RESULTS: Across various indicators of diet
      quality, an association with academic performance was observed. Students with
      decreased overall diet quality were significantly more likely to perform poorly
      on the assessment. Girls performed better than boys as did children from
      socioeconomically advantaged families. Children attending better schools and
      living in wealthy neighborhoods also performed better. CONCLUSIONS: These
      findings demonstrate an association between diet quality and academic performance
      and identify specific dietary factors that contribute to this association.
      Additionally, this research supports the broader implementation and investment in
      effective school nutrition programs that have the potential to improve student
      access to healthy food choices, diet quality, academic performance, and, over the
      long term, health.

PMID- 18336681
TI  - A pilot study to examine the effects of a nutrition intervention on nutrition
      knowledge, behaviors, and efficacy expectations in middle school children.
AB  - BACKGROUND: This was a pilot study to determine the impact of the Michigan Model
      (MM) Nutrition Curriculum on nutrition knowledge, efficacy expectations, and
      eating behaviors in middle school students. METHODS: The study was conducted in a
      large metropolitan setting and approved by the Institutional Review Board. The
      participants for this study were divided into an intervention group (n = 407) and
      a control group (n = 169). An MM instructor trained health teachers in the use of
      the curriculum, and the teacher subsequently taught the curriculum to students in
      the intervention group. A valid and reliable questionnaire was used to determine
      pre-post differences. It consisted of 3 subscales assessing eating habits,
      nutrition knowledge, and efficacy expectations toward healthy eating. Subscale
      scores were analyzed using a 2 groups (intervention vs control) x 2 times (pre vs
      post) analysis of variance. RESULTS: The intervention group increased their
      nutrition knowledge at post. There was also a significant main effect for groups
      in the subscales "Eating Behaviors" and "Efficacy Expectations Regarding Healthy
      Eating." Subsequent post hoc analysis revealed that the intervention group was
      significantly more likely to eat fruits and vegetables and less likely to eat
      junk food than the control group. Students in the intervention group also felt
      more confident that they could eat healthy. CONCLUSIONS: The results of this
      pilot study suggest that the MM Nutrition Curriculum delivered by trained
      professionals resulted in significant positive changes in both nutrition
      knowledge and behaviors in middle school children. Further research needs to be
      conducted to determine the long-term impact.

PMID- 18336682
TI  - Associations of health risk behaviors with school absenteeism. Does having
      permission for the absence make a difference?
AB  - BACKGROUND: Nearly 10% of students enrolled in US public schools are absent
      daily. Although previous research has shown associations of school absenteeism
      with participation in risk behaviors, it is unclear if these associations vary by
      whether the absence was excused. The purpose of this study was to examine the
      associations of health risk behaviors with being absent from school with and
      without permission among high school students. METHODS: During spring 2004,
      questionnaires similar to the Youth Risk Behavior Survey questionnaire were
      completed by 4517 ninth- and eleventh-grade students. Responses to items
      assessing frequency of school absences during the past 30 days for any reason and
      without permission were combined to create a variable coded as absent on: 0 days;
      > or =1 day, all with permission (WP); and > or =1 day, at least 1 day without
      permission (WOP). Logistic regression analyses controlling for gender, grade, and
      race/ethnicity examined the association of risk behaviors with absenteeism.
      RESULTS: Controlling for demographic variables, compared to students who were
      absent 0 days, students who were absent WP had significantly higher odds of
      engaging in 25 of 55 risk behaviors examined and students who were absent WOP had
      significantly higher odds of engaging in 43 of the 55 behaviors. Students who
      were absent WOP also had approximately twice the odds of engaging in risk
      behaviors compared to students who were absent WP. CONCLUSIONS: School
      absenteeism, with and without permission, is associated with risk behaviors.
      Schools should recognize absenteeism for any reason as a warning sign for a
      variety of risk behaviors.

PMID- 18336683
TI  - Inexpensive and time-efficient hand hygiene interventions increase elementary
      school children's hand hygiene rates.

PMID- 18336684
TI  - An analysis of the doctor-patient relationship using Patch Adams.

PMID- 18336686
TI  - A perspective on chronic illness.

PMID- 18336687
TI  - Living with chronic illness: a phenomenological study of the health effects of
      the patient-provider relationship.
AB  - PURPOSE: To understand the patient-healthcare provider (HCP) relationship from
      the lived experience of women with chronic disease and determine how this
      relationship affects women's health. DATA SOURCES: Narrative accounts of 25
      women's relationships with HCPs in repeated group and individual interviews were
      audio-taped and transcribed verbatim. Interpretive phenomenology was used to
      explore the data using three interconnected modes of paradigm cases, exemplars,
      and themes. CONCLUSIONS: Women with chronic disease believed their health was
      significantly affected by their relationships with HCPs. They experienced a
      greater sense of well-being and security in connected relationships and had more
      confidence and motivation to manage their illness. IMPLICATIONS FOR PRACTICE:
      This research suggests that for women with chronic disease, relationships with
      HCPs that are connected, and characterized by partnership, and personableness
      result in the women feeling better in many dimensions. The context of today's
      healthcare system often pushes the nurse practitioner (NP) to provide care more
      attuned to medical issues, leaving little time for the development of connected
      relationships. In spite of this pressure, NPs need to strive to develop
      relationships with patients that are intersubjective/connected.

PMID- 18336688
TI  - The illness beliefs, perceptions, and practices of Filipino Americans with
      hypertension.
AB  - PURPOSE: The purpose of this study was to describe the illness beliefs,
      perceptions, and practices of Filipino Americans (FAs) with hypertension (HTN) to
      reveal their explanatory models (EMs) of the illness. DATA SOURCES: Audiotapes
      and transcripts of focus group interviews and observational notes were subjected
      to content analysis. Medical records and related empirical studies provided
      supporting data. CONCLUSIONS: In general, the EMs of FAs with HTN correspond to
      the biomedical model in relation to causes, consequences, and treatment of HTN.
      However, in spite of this biomedical knowledge, FAs with HTN have difficulty
      maintaining the required lifestyle changes and adhering to the medication regimen
      to control their illness. IMPLICATIONS FOR PRACTICE: It is important for NPs to
      assess the EMs of FAs with HTN, including their use of traditional folk remedies
      and practitioners of folk medicine. The challenge is to provide cardiovascular
      health promotion and education in a culturally sensitive, congruent, and tailored
      manner to FAs with HTN to help them control their illness.

PMID- 18336689
TI  - Implications of the biology of weight regulation and obesity on the treatment of
      obesity.
AB  - PURPOSE: The purposes of this article are to provide a brief review of the
      complex biology of weight regulation and obesity, to explain some of the effects
      of diet and exercise on the biology of weight regulation and obesity, and to
      propose a coherent way to assess and treat people related to weight and obesity.
      DATA SOURCES: Scientific publications, clinical guidelines, and government
      sources. CONCLUSIONS: Obesity is a complex problem requiring an understanding of
      how interventions interact with the biology of weight regulation in people who
      are obese. Promoting health in obese people requires a focus on improving insulin
      sensitivity. IMPLICATIONS FOR PRACTICE: Helping individuals maintain normal
      weight throughout life is important in order to keep the long- and short-term
      weight signals in balance and reflective of true energy requirements. Exercise is
      associated with loss of total and abdominal adipose tissue and improved insulin
      sensitivity. Diets inducing gradual weight loss are less likely to stimulate
      appetite. Diets should include antioxidants to neutralize the increase in free
      radical production associated with obesity and exercise. Other interventions in
      the treatment of obesity may include treating sleep deficits and the dysregulated
      endocannabinoid system.

PMID- 18336690
TI  - Cost-efficient treatment for uninsured or underinsured patients with
      hypertension, depression, diabetes mellitus, insomnia, and gastroesophageal
      reflux.
AB  - PURPOSE: As the number of uninsured and underinsured patients in the United
      States continues to rise, savvy nurse practitioners (NPs) must balance quality of
      care with cost of drugs. This article reviews evidence-based treatments in light
      of prescribing the most cost-efficient medications. DATA SOURCES: Searches of
      electronic databases including MEDLINE, MEDLINEPlus, EBSCO, PubMed, CINAHL,
      Clinical Pharmacology, Biomedical Reference Collection--Basic, Health Source-
      Consumer Edition, Health Source--Nursing/Academic Edition, Ovid, and the Cochrane
      Library Online. CONCLUSIONS: As the role of NP continues to evolve, it is
      important for NPs to establish themselves as economically conscious healthcare
      providers, striking a delicate balance between providing quality and cost
      efficient care. An NP's familiarity with cost-efficient treatment options for
      common diagnoses such as hypertension, depression, diabetes mellitus, insomnia,
      and gastroesophageal reflux disorders can help ease the economic burden uninsured
      and underinsured patients endure, especially with respect to prescription drugs,
      and improve compliance with medication regimens. IMPLICATIONS FOR PRACTICE: NPs
      should acquire knowledge on how to best treat uninsured or underinsured patients
      in the most cost-efficient manner. Knowledge of prescription drug cost is one
      tool an NP can use to encourage patient compliance, improving the overall health
      of uninsured or underinsured individuals.

PMID- 18336691
TI  - Health goals among primary care patients.
AB  - PURPOSE: To identify individuals' health goals and describe their preferences in
      attaining those goals and to explore associations of type of goals with
      individual characteristics. DATA SOURCES: In a descriptive study, 60 adult
      patients from primary care clinics completed written questionnaires anonymously.
      Content analyses and frequencies were used to summarize data. CONCLUSIONS: Health
      promotion interventions could be more effective if they were customized, in part,
      to individuals' health goals. There are few evidence-based descriptions of
      individuals' own health goals and their preferences in how to pursue them.
      Participants in this study shared common goals to get in shape, lose weight, and
      change consumption. Participants preferred to meet initially with practitioners
      to obtain advice and to connect subsequently by telephone for monitoring.
      IMPLICATIONS: Participants did want to improve their health. More specific
      understanding of such goals and preferences is needed to guide future
      interventions. Findings can inform clinicians and guide researchers in how to
      design health behavior interventions.

PMID- 18336692
TI  - Alliance not compliance: coaching strategies to improve type 2 diabetes outcomes.
AB  - PURPOSE: To explore strategies for improving patient outcomes in type 2 diabetes.
      DATA SOURCES: The literature related to type 2 diabetes management, behavior
      change, communication, diabetes self-management, and coaching. CONCLUSIONS: The
      strategies currently suggested for improving patient outcomes, e.g., increasing
      provider adherence to evidence-based management guidelines, streamlining practice
      systems, and promoting patient lifestyle changes through intensive education,
      have produced mixed outcomes. Of the many complexities involved in managing type
      2 diabetes, motivating patients to change behavior may be the most challenging. A
      suggestion for improving patient self-management of type 2 diabetes is to use
      coaching communication within a framework of behavior change in the context of
      the primary care encounter between nurse practitioners (NPs) and their patients.
      IMPLICATIONS FOR PRACTICE: Given the varied outcomes of current strategies,
      coaching by NPs may provide a feasible alternative for improving patient outcomes
      in type 2 diabetes. Coaching communication can be implemented during office
      visits as an intervention without cost. To effectively implement this approach,
      however, practicing NPs and NP students need more formal education in this
      expected but underdeveloped NP role competency. NPs are called upon to contribute
      to the body of knowledge needed to validate the merits of coaching for their
      patients.

PMID- 18336693
TI  - Implementation and outcomes of group medical appointments in an outpatient
      specialty care clinic.
AB  - PURPOSE: To describe the outcomes of a nurse practitioner (NP)-facilitated group
      medical appointment (GMA) intervention for chronic obstructive pulmonary disease
      (COPD) clients in a pulmonary practice in the Midwest. DATA SOURCES: Medical
      records from a convenience sample of six established pulmonary patients in a
      Midwest specialty clinic who received care in a group format were retrospectively
      audited. Outcome measures included examination of changes in the utilization of
      healthcare services, exercise tolerance, and use of nonpharmacological and
      pharmacological interventions pre- and postparticipation in the GMA program.
      CONCLUSIONS: NP-facilitated GMAs are feasible and can help improve health
      outcomes. Results showed a significant increase in exercise tolerance measured by
      6-min walk distance. Anecdotally, patient and provider response to the GMA was
      very positive. IMPLICATIONS FOR PRACTICE: The GMA format is an innovative
      solution for the management of chronic disease patients that is comprehensive,
      time efficient, reimbursable, and well suited to NP practice. GMAs can be
      implemented in most practice settings.

PMID- 18336695
TI  - Trends in organ donation and transplantation in the United States, 1997-2006.

PMID- 18336696
TI  - Organ donation and utilization in the United States, 1997-2006.
AB  - Deceased organ donation has increased rapidly since 2002, coinciding with
      implementation of the Organ Donation Breakthrough Collaborative. The increase in
      donors has resulted in a corresponding increase in the numbers of kidney, liver,
      lung and intestinal transplants. While transplants for most organs have
      increased, discard and nonrecovery rates have not improved or have increased,
      resulting in a decrease in organs recovered per donor (ORPD) and organs
      transplanted per donor (OTPD). Thus, the expansion of the consent and recovery of
      incremental donors has frequently outpaced utilization. Meaningful increases in
      multicultural donation have been achieved, but donations continue to be lower
      than actual rates of transplantation and waiting list registrations for these
      groups. To counteract the decline in living donation, mechanisms such as paired
      donation and enhanced incentives to organ donation are being developed. Current
      efforts of the collaborative have focused on differentiating ORPD and OTPD
      targets by donor type (standard and expanded criteria donors and donors after
      cardiac death), utilization of the OPTN regional structure and enlisting centers
      to increase transplants to match increasing organ availability.

PMID- 18336697
TI  - Pediatric transplantation in the United States, 1997-2006.
AB  - This article represents the sixth annual review of the current state of pediatric
      transplantation in the United States from the Scientific Registry of Transplant
      Recipients (SRTR). It presents updated trends, discussion of analyses presented
      during the year by the SRTR to the committees of the Organ Procurement and
      Transplantation Network (OPTN) and discussion of important issues currently
      facing pediatric organ transplantation. Unless otherwise stated, the statistics
      in this article are drawn from the reference tables of the 2007 OPTN/SRTR Annual
      Report. In this article, pediatric patients are defined as candidates, recipients
      or donors aged 17 years or less. Data for both graft and patient survival are
      reported as unadjusted survival, unless otherwise stated (adjusted patient and
      graft survival are available in the reference tables). Short-term survival (3
      month and 1 year) reflects outcomes for transplants performed in 2004 and 2005; 3
      year survival reflects transplants from 2002 to 2005; and 5-year survival reports
      on transplants performed from 2000 to 2005. Details on the methods of analysis
      employed may be found in the reference tables themselves or in the technical
      notes of the 2007 OTPN/SRTR Annual Report, both available online at
      http://www.ustransplant.org.

PMID- 18336698
TI  - Kidney and pancreas transplantation in the United States, 1997-2006: the HRSA
      Breakthrough Collaboratives and the 58 DSA Challenge.
AB  - Growth in the number of active patients on the kidney transplant waiting list has
      slowed. Projections based on the most recent 5-year data suggest the total
      waiting list will grow at a rate of 4138 registrations per year, whereas the
      active waiting list will increase at less than one-sixth that rate, or 663
      registrations per year. The last 5 years have seen a small trend toward improved
      unadjusted allograft survival for living and deceased donor kidneys. Since 2004
      the overall number of pancreas transplants has declined. Among pancreas
      recipients, those with simultaneous kidney-pancreas transplants experienced the
      highest pancreas graft survival rates. In response to the ongoing shortage of
      deceased donor organs, the US Health Resources and Services Administration
      launched the Organ Donation Breakthrough Collaborative in September 2003 and the
      Organ Transplantation Breakthrough Collaborative (OTBC) in October 2005. The 58
      DSA Challenge is prominent among the goals adopted by the OTBC. Its premise: were
      each of the 58 existing donation service areas to increase the number of kidney
      transplants performed within their boundaries by 10 per month, an additional 7000
      transplants over current annual levels would result. Such an increase could
      potentially eliminate the national kidney transplantation waiting list by 2030.

PMID- 18336699
TI  - Liver and intestine transplantation in the United States, 1997-2006.
AB  - Liver transplantation in 2006 generally resembled previous years, with fewer
      candidates waiting for deceased donor liver transplants (DDLT), continuing a
      trend initiated with the implementation of the model for end-stage liver disease
      (MELD). Candidate age distribution continued to skew toward older ages with fewer
      children listed in 2006 than in any prior year. Total transplants increased due
      to more DDLT with slightly fewer living donor liver transplants (LDLT). Waiting
      list deaths and time to transplant continued to improve. In 2006, there also were
      fewer DDLT for patients with MELD <15, fewer pediatric Status 1A/B transplants
      and more transplants from donation after cardiac death (DCD) donors. Adjusted
      patient and graft survival rates were similar for LDLT and DDLT. This article
      also contains in-depth analyses of transplantation for hepatocellular carcinoma
      (HCC). Recipients with HCC had lower adjusted 3-year posttransplant survival than
      recipients without HCC. HCC recipients who received pretransplant ablative
      treatments had superior adjusted 3-year posttransplant survival compared to HCC
      recipients who did not. Intestinal transplantation continued to slowly increase
      with the largest number of candidates on the waiting list since 1997. Survival
      rates have increased over time. Small children waiting for intestine grafts
      continue to have the highest waiting list mortality.

PMID- 18336700
TI  - Heart and lung transplantation in the United States, 1997-2006.
AB  - This article highlights trends in heart and lung transplantation between 1997 and
      2006, drawing on data from the OPTN and SRTR. The total number of candidates
      actively awaiting heart transplantation declined by 45% over the last decade,
      dropping from 2414 patients in 1997 to 1327 patients in 2006. The overall death
      rates among patients awaiting heart transplantation declined over the same
      period. The distribution of recipients among the different status groups at the
      time of heart transplantation changed little between the inception of the new
      classification system in 1999 and 2005. Deaths in the first year after heart
      transplantation have steadily decreased. At the end of 2006, 2885 candidates were
      awaiting a lung transplant, up 10% from the 1997 count. The median time-to
      transplant for listed patients decreased by 87% over the decade, dropping from
      1053 days in 1997 to 132 days in 2006. Selection for listing and transplantation
      has shifted toward more urgent patients since the May 2005 implementation of a
      new lung allocation system based on survival benefit and urgency rather than
      waiting time. Only 31 heart-lung transplants were performed in 2006, down from a
      high of 62 in 1997.

PMID- 18336701
TI  - Transplants in Foreign Countries Among Patients Removed from the US Transplant
      Waiting List.
AB  - Transplant tourism, where patients travel to foreign countries specifically to
      receive a transplant, is poorly characterized. This study examined national data
      to determine the minimum scope of this practice. US national waiting list removal
      data were analyzed. Waiting list removals for transplant without a corresponding
      US transplant in the database were reviewed via a data validation query to
      transplant centers to identify foreign transplants. Additionally, waiting list
      removal records with text field entries indicating a transplant abroad were
      identified. We identified 373 foreign transplants (173 directly noted; 200 from
      data validation); most (89.3%) were kidney transplants. Between 2001 and 2006,
      the annual number of waiting list removals for transplant abroad increased. Male
      sex, Asian race, resident and nonresident alien status and college education were
      significantly and independently associated with foreign transplant. Recipients
      from 34 states, plus the District of Columbia, received foreign transplants in 35
      countries, led by China, the Philippines and India. Transplants in foreign
      countries among waitlisted candidates in the US are increasingly performed. The
      data reported here represent the minimum number of cases and the full extent of
      this practice cannot be determined using existing data. Additional reporting
      requirements are needed.

PMID- 18336702
TI  - Calculating life years from transplant (LYFT): methods for kidney and kidney
      pancreas candidates.
AB  - The Organ Procurement and Transplantation Network (OPTN) Kidney Committee is
      considering a proposal for a new deceased donor kidney allocation system. Among
      the components under consideration is a strategy to rank candidates in part by
      the estimated incremental years of life that are expected to be achieved with a
      transplant from a specific available deceased donor, computed as the difference
      in expected median lifespan with that transplant compared with remaining on
      dialysis. This concept has been termed life years from transplant or LYFT. Median
      lifespans could be calculated, based on objective medical criteria, for each
      candidate when a deceased donor kidney becomes available, based on Cox regression
      models using current candidate and donor medical information. The distribution of
      the calculated LYFT scores for an average nonexpanded criteria donor kidney is
      similar across candidate sex, race/ethnicity, insurance status and, with the
      exception of diabetes, diagnosis. LYFT scores tend to be higher for younger
      candidates and lower for diabetics receiving a kidney-alone rather than a
      simultaneous kidney-pancreas transplant. Prioritizing candidates with higher LYFT
      scores for each available kidney could substantially increase total years of life
      among both transplant candidates and recipients. LYFT is also a powerful metric
      for assessing trends in allocation outcomes and for comparing alternative
      allocation systems.

PMID- 18336703
TI  - SRTR program-specific reports on outcomes: a guide for the new reader.
AB  - Differences in outcomes indeed exist among transplant programs and organ
      procurement organizations (OPO). A growing set of tools are available from the
      Scientific Registry of Transplant Recipients (SRTR) to measure and assess these
      outcomes in the different phases of the transplant process. These tools are not
      intended to compare two individual programs, rather to help identify programs
      whose practices may need further scrutiny, to be either avoided, corrected or
      emulated. To understand which differences in outcomes might be due to underlying
      differences in populations served and which might be due to differences in
      treatment, it is important to compare outcomes to 'risk-adjusted' expected
      values. Further, it is important to recognize and assess the role that random
      chance may play in these outcomes by considering the p-value or confidence
      interval of each estimate. We present the reader with a basic explanation of
      these tools and their interpretation in the context of reading the SRTR Program
      Specific Reports. We describe the intended audience of these reports, including
      patients, monitoring and process improvement bodies, payers and others such as
      the media. Use of these statistics in a way that reflects a basic understanding
      of these concepts and their limitations is beneficial for all audiences.

PMID- 18336704
TI  - Philosophy and palliative care.

PMID- 18336705
TI  - Human nature: a foundation for palliative care.
AB  - The Aristotelian-Thomist philosopher holds that human intellectual knowledge is
      possible because of the order in the world and natural human capacities. It is
      the position of this paper that there is a shared human form or nature that
      unites all humanity as members of the same kind. Moral treatment is due to every
      human being because they are human, and is not based upon expression of
      abilities. Humans have substantial dynamic existence in the world, an existence
      which overflows in expressive relationships. As both patient and health
      professional are human, human nature forms the natural foundation of health care.
      This paper looks towards human nature for moral guidance. The therapeutic
      relationship is seen as a part of the interpersonal moral space formed by human
      relationality, which tends towards community - in this case, the healthcare
      system. The therapeutic relationship is also a source of moral responsibility, as
      illness makes the patient vulnerable, while knowledge and nursing capacities
      generate in the nurse a duty to care. Nursing theory serves to connect
      philosophical reflection and nursing practice. Imogene King's conceptual system
      and theory of Goal Attainment is the theory that follows from the perspective of
      human person being presented. This synthesis of philosophy and theory is
      developed with the goal of shedding light on healthcare decisions in palliative
      care. The article concludes with the acknowledgement that the complexity of
      contextualized individual decisions requires the insight and discipline of the
      moral practitioner, and provides some thoughts on how education, development, and
      refinement transform an individual into a nurse.

PMID- 18336706
TI  - The dying person: an existential being until the end of life.
AB  - This article explores the experience of death from the perspective of existential
      philosophy, for the purpose of finding ways to humanize end-of-life nursing care.
      A person in his or her final days is seen by the caregiver as a being seeking the
      continual creation of his human becoming, from the experience of sickness to
      death. From the moment the torment of suffering begins, a person needs a presence
      of humanistic professionalism that embraces the values of the nursing profession.

PMID- 18336707
TI  - A conversation on diverse perspectives of spirituality in nursing literature.
AB  - Spirituality has long been considered a dimension of holistic palliative care.
      However, conceptualizations of spirituality are in transition in the nursing
      literature. No longer rooted within religion, spirituality is increasingly being
      defined by the universal search for meaning, connectedness, energy, and
      transcendence. To be human is to be spiritual. Some have argued that the concept
      of spirituality in the nursing literature has become so generic that it is no
      longer meaningful. A conceptualization that attempts to be all-encompassing of
      what it means to live a human life has a tendency to render invisible the
      differences that make life meaningful. For palliative patients in particular, a
      generic approach may obscure and relativize the important values and beliefs that
      inform the critical questions that many patients grapple with at end of life. A
      different approach to conceptualizing spirituality can be achieved through the
      use of typologies. Rather than obscuring difference, categories are constructed
      to illuminate how spirituality is understood within a diverse society and how
      those understandings might influence patient-provider relationships. What follows
      in this article is a dialogue illustrating one typology of spirituality
      constructed from a review of selected nursing literature. The hypothetical
      narrator and three participants, representing the positions of theism, monism,
      and humanism, discuss their understandings of spirituality and religion, and how
      those understandings influence the intersections between nursing ontology,
      epistemology, and spiritual care.

PMID- 18336708
TI  - Palliative care for people with Alzheimer's disease.
AB  - The task of aligning the philosophical and clinical perspectives on ethics is a
      challenging one. Clinical practice informs philosophy, not merely by supplying
      cases, but through shaping and testing philosophical concepts in the reality of
      the clinical world. In this paper we explore several aspects of the relationship
      between the philosophical and the clinical within a framework of palliative care
      for people living with Alzheimer's disease. We suggest that health professionals
      have a moral obligation to question previous assumptions concerning the quality
      of life among people with Alzheimer's, and to address the question: does the
      concept of palliative care properly embrace people with severe dementia? We
      propose an ethic of palliative care for people with Alzheimer's that is based,
      not on the traditionally understood principle of autonomy, but on the need to
      listen to those living with the disease, acknowledging their profound loss of
      cognitive abilities, with a focus on preventing and relieving suffering, and
      improving the individual's quality of life.

PMID- 18336709
TI  - Human understanding in dialogue: Gadamer's recovery of the genuine.
AB  - In this paper, the notion of the genuine as it relates to conversation is
      explored based on the work of H. G. Gadamer in his major work, Truth and Method
      (1989). The application of the genuine to human interaction and understanding in
      the context of qualitative research is examined. In addition, possible outcomes
      of the researcher's philosophical hermeneutic position, as exemplified through
      the use of the genuine conversation in her work, are discussed. Both the problem
      as well as the productivity of self-application and prejudice are addressed
      through the lens of the genuine conversation. We then illustrate the character of
      interviewing and interpretation of text as research practices that can be
      informed by Gadamer's philosophical hermeneutics while resisting methodology as a
      necessary feature of research inquiry.

PMID- 18336710
TI  - A reply to 'Spirituality and nursing: a reductionist approach' by John Paley.

PMID- 18336715
TI  - International philosophy of Nursing Conference 2007. Conference review.

PMID- 18336716
TI  - Sustained virological and biochemical responses to lamivudine and adefovir
      dipivoxil combination in a chronic hepatitis B infection despite mutations
      conferring resistance to both drugs.
AB  - BACKGROUND: Sequential monotherapies of nucleotide analogs used in chronic
      hepatitis B treatment can lead to the selection of a resistance mutation to each
      antiviral drug. CASE PRESENTATION: A patient with chronic hepatitis B was
      successively treated with lamivudine monotherapy, lamivudine-adefovir dual
      therapy, adefovir monotherapy and again with an adefovir-lamivudine dual therapy.
      Lamivudine-associated mutations (rtL180M and rtM204V/I) followed by adefovir
      associated mutations (rtN236T and rtA181V) emerged during the two monotherapy
      regimens. Despite the presence of rtM204V/I, rtA181V, and rtN236T mutations at
      the beginning of the second dual therapy, sustained biochemical and virological
      responses have been observed thus far after 23 months. CONCLUSION: This case
      illustrates that rtM204V/I, rtA181V, and rtN236T resistance mutations can coexist
      in a patient but do not preclude the recycling of lamivudine and adefovir in
      combination therapy, when no other therapeutic choices are available.

PMID- 18336717
TI  - Functional diversification of duplicate genes through subcellular adaptation of
      encoded proteins.
AB  - BACKGROUND: Gene duplication is the primary source of new genes with novel or
      altered functions. It is known that duplicates may obtain these new functional
      roles by evolving divergent expression patterns and/or protein functions after
      the duplication event. Here, using yeast (Saccharomyces cerevisiae) as a model
      organism, we investigate a previously little considered mode for the functional
      diversification of duplicate genes: subcellular adaptation of encoded proteins.
      RESULTS: We show that for 24-37% of duplicate gene pairs derived from the S.
      cerevisiae whole-genome duplication event, the two members of the pair encode
      proteins that localize to distinct subcellular compartments. The propensity of
      yeast duplicate genes to evolve new localization patterns depends to a large
      extent on the biological function of their progenitor genes. Proteins involved in
      processes with a wider subcellular distribution (for example, catabolism)
      frequently evolved new protein localization patterns after duplication, whereas
      duplicate proteins limited to a smaller number of organelles (for example, highly
      expressed biosynthesis/housekeeping proteins with a slow rate of evolution)
      rarely relocate within the cell. Paralogous proteins evolved divergent
      localization patterns by partitioning of ancestral localizations
      ('sublocalization'), but probably more frequently by relocalization to new
      compartments ('neolocalization'). We show that such subcellular reprogramming may
      occur through selectively driven substitutions in protein targeting sequences.
      Notably, our data also reveal that relocated proteins functionally adapted to
      their new subcellular environments and evolved new functional roles through
      changes of their physico-chemical properties, expression levels, and interaction
      partners. CONCLUSION: We conclude that protein subcellular adaptation represents
      a common mechanism for the functional diversification of duplicate genes.

PMID- 18336718
TI  - The Rho-activating CNF1 toxin from pathogenic E. coli: a risk factor for human
      cancer development?
AB  - Nowadays, there is increasing evidence that some pathogenic bacteria can
      contribute to specific stages of cancer development. The concept that bacterial
      infection could be involved in carcinogenesis acquired a widespread interest with
      the discovery that H. pylori is able to establish chronic infections in the
      stomach and that this infection is associated with an increased risk of gastric
      adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Chronic infections
      triggered by bacteria can facilitate tumor initiation or progression since,
      during the course of infection, normal cell functions can come under the control
      of pathogen factors that directly manipulate the host regulatory pathways and the
      inflammatory reactions.Renowned publications have recently corroborated the
      molecular mechanisms that link bacterial infections, inflammation and cancer,
      indicating certain strains of Escherichia coli as a risk factor for patients with
      colon cancer. E. coli is a normal inhabitant of the human intestine that becomes
      highly pathogenic following the acquisition of virulence factors, including a
      protein toxin named cytotoxic necrotizing factor 1 (CNF1). This toxin permanently
      activates the small GTP-binding proteins belonging to the Rho family, thus
      promoting a prominent polymerization of the actin cytoskeleton as well as a
      number of cellular responses, including changes in protein expression and
      functional modification of the cell physiology. CNF1 is receiving an increasing
      attention as a putative factor involved in transformation because of its ability
      to: (i) induce COX2 expression, an immediate-early gene over-expressed in some
      type of cancers; (ii) induce a long-lasting activation of the transcription
      factor NF-kB, a largely accepted marker of tumor cells; (iii) protect epithelial
      cells from apoptosis; (iv) ensue the release of pro-inflammatory cytokines in
      epithelial and endothelial cells; and (v) promote cellular motility. As cancer
      may arise through dysfunction of the same regulatory systems, it seems likely
      that CNF1-producing E. coli infections can contribute to tumor development.This
      review focuses on the aspects of CNF1 activity linked to cell transformation with
      the aim of contributing to the identification of a possible carcinogenic agent
      from the microbial world.

PMID- 18336719
TI  - Walking a mile in their patients' shoes: empathy and othering in medical
      students' education.
AB  - One of the major tasks of medical educators is to help maintain and increase
      trainee empathy for patients. Yet research suggests that during the course of
      medical training, empathy in medical students and residents decreases. Various
      exercises and more comprehensive paradigms have been introduced to promote
      empathy and other humanistic values, but with inadequate success. This paper
      argues that the potential for medical education to promote empathy is not easy
      for two reasons: a) Medical students and residents have complex and mostly
      unresolved emotional responses to the universal human vulnerability to illness,
      disability, decay, and ultimately death that they must confront in the process of
      rendering patient care b) Modernist assumptions about the capacity to protect,
      control, and restore run deep in institutional cultures of mainstream biomedicine
      and can create barriers to empathic relationships. In the absence of appropriate
      discourses about how to emotionally manage distressing aspects of the human
      condition, it is likely that trainees will resort to coping mechanisms that
      result in distance and detachment. This paper suggests the need for an
      epistemological paradigm that helps trainees develop a tolerance for imperfection
      in self and others; and acceptance of shared emotional vulnerability and
      suffering while simultaneously honoring the existence of difference. Reducing the
      sense of anxiety and threat that are now reinforced by the dominant medical
      discourse in the presence of illness will enable trainees to learn to emotionally
      contain the suffering of their patients and themselves, thus providing a
      psychologically sound foundation for the development of true empathy.

PMID- 18336720
TI  - Midlife diagnosis of Refsum disease in siblings with retinitis pigmentosa -- the
      footprint is the clue: a case report.
AB  - INTRODUCTION: Refsum disease is a potentially lethal and disabling condition
      associated with retinitis pigmentosa in which early treatment can prevent some of
      the systemic manifestations. CASE PRESENTATION: We present the cases of two
      brothers with a diagnosis of retinitis pigmentosa from childhood in whom Refsum
      disease was subsequently diagnosed midlife, after routine enquiry into hand and
      feet abnormalities. Subsequent treatment through dietary modification stabilised
      visual impairment and has prevented development of neurological complications to
      date. CONCLUSION: It is therefore important to consider the diagnosis of Refsum
      disease in any patient with autosomal recessive or simplex retinitis pigmentosa,
      and to enquire about the presence of "unusual" feet or hands in such patients.

PMID- 18336721
TI  - The CORONIS Trial. International study of caesarean section surgical techniques:
      a randomised fractional, factorial trial.
AB  - BACKGROUND: Caesarean section is one of the most commonly performed operations on
      women throughout the world. Rates have increased in recent years - about 20-25%
      in many developed countries. Rates in other parts of the world vary widely.A
      variety of surgical techniques for all elements of the caesarean section
      operation are in use. Many have not yet been rigorously evaluated in randomised
      controlled trials, and it is not known whether any are associated with better
      outcomes for women and babies. Because huge numbers of women undergo caesarean
      section, even small differences in post-operative morbidity rates between
      techniques could translate into improved health for substantial numbers of women,
      and significant cost savings. DESIGN: CORONIS is a multicentre, fractional,
      factorial randomised controlled trial and will be conducted in centres in
      Argentina, Ghana, India, Kenya, Pakistan and Sudan. Women are eligible if they
      are undergoing their first or second caesarean section through a transverse
      abdominal incision. Five comparisons will be carried out in one trial, using a 2
      x 2 x 2 x 2 x 2 fractional factorial design. This design has rarely been used,
      but is appropriate for the evaluation of several procedures which will be used
      together in clinical practice. The interventions are:* Blunt versus sharp
      abdominal entry* Exteriorisation of the uterus for repair versus intra-abdominal
      repair* Single versus double layer closure of the uterus* Closure versus non
      closure of the peritoneum (pelvic and parietal)* Chromic catgut versus
      Polyglactin-910 for uterine repairThe primary outcome is death or maternal
      infectious morbidity (one or more of the following: antibiotic use for maternal
      febrile morbidity during postnatal hospital stay, antibiotic use for
      endometritis, wound infection or peritonitis) or further operative procedures; or
      blood transfusion. The sample size required is 15,000 women in total; at least
      7,586 women in each comparison. DISCUSSION: Improvements in health from
      optimising caesarean section techniques are likely to be more significant in
      developing countries, because the rates of postoperative morbidity in these
      countries tend to be higher. More women could therefore benefit from improvements
      in techniques. TRIAL REGISTRATION: The CORONIS Trial is registered in the Current
      Controlled Trials registry. ISCRTN31089967.

PMID- 18336722
TI  - Living alone is a risk factor for mortality in men but not women from the general
      population: a prospective cohort study.
AB  - BACKGROUND: During the past decades a rising trend of living alone can be
      observed in the population especially in urban areas. Living alone is considered
      a psychosocial risk factor. We studied the relationship between living alone,
      cardiovascular risk factors and mortality. METHODS: We analysed data from the
      population-based MONICA/KORA cohort study including 3596 men and 3420 women of at
      least one of three surveys carried out between 1984 and 1995 in the region of
      Augsburg, Germany. They were between 45 and 74 years old and were followed-up
      until 31 December 2002. During follow-up 811 men and 388 women died. Cox
      proportional hazards analysis was used to examine the association between living
      alone and mortality. RESULTS: Altogether 260 men (7%) and 620 women (18%) were
      living alone at baseline. Men, who lived alone, were less well educated, had
      fewer children and friends, and they smoked significantly more than other men.
      Women, living alone, were also significantly more often current smokers and had
      less children and friends, but they were more often better educated than
      cohabitating women. The latter group showed a higher proportion of obese and
      hypertensive women. Men living alone had a twofold risk to die after
      multivariable adjustment (hazard ratio = 1.96; p < 0.0001; 95% confidence
      interval 1.56-2.46). This was not the case for women. CONCLUSION: Living alone is
      an independent risk factor for mortality in men. It is unclear whether living
      alone causes an increased mortality or whether predisposition for increased
      mortality is responsible for men living alone.

PMID- 18336723
TI  - The impact of home cleaning on quality of life for homes with asthmatic children.
AB  - Treatment with common household bleach containing hypochlorite destroys dust
      mites and denatures protein allergens. The purpose of this study was to determine
      if home use of hypochlorite products results in lowered exposure to bacteria,
      fungi, and protein allergens and improved quality of life (QOL) for asthmatic
      persons in the home. Asthmatic and nonasthmatic households containing at least
      three persons (between 2 and 17 years of age) were recruited. Households were
      supplied one of three sets of cleaning products (regular products, some
      containing hypochlorite; regular products plus three additional products with
      dilute hypochlorite; control, no products). Participants were supplied with
      cleaning instructions and asthma education. The control group was instructed to
      clean as usual. Participants completed general health and QOL questionnaires.
      Asthmatic participants completed an additional asthma QOL questionnaire. Families
      participated in the study for 8 weeks and completed the full set of questions
      every 2 weeks. Homes were visited at the beginning of the study and twice
      thereafter at monthly intervals. Samples evaluated were surface bacteria, viable
      and nonviable airborne spores, and dust antigen content. Reductions in surface
      bacteria, airborne fungal spores, and dust antigen levels were achieved.
      Significant improvement in general health parameters was seen for the asthmatic
      product groups over the control group. Significant improvement in general QOL and
      asthma-specific QOL was seen in the asthmatic group. Emphasis on cleaning and
      cleaning education combined with hypochlorite-based cleaning supplies resulted in
      significantly improved QOL for families with asthmatic children.

PMID- 18336724
TI  - Expression of survivin and enhanced polypogenesis in nasal polyps.
AB  - BACKGROUND: The pathogenesis of nasal polyps still is not clear. This disease is
      believed to be inflammation related. Previous research has indicated that
      apoptosis in inflammatory cells is an important factor in the resolution of
      inflammation. Survivin is regarded as a novel member of the group of inhibitors
      of apoptosis proteins. It is overexpressed in a number of tumor types. The
      objective of this study was to investigate the expression of the survivin gene in
      human nasal polyps. METHODS: We investigated the expression of survivin in nasal
      polyps of adult patients with chronic rhinosinusitis. Specimens of nasal polyps
      were harvested during endonasal sinus surgery (n=22), and the normal mucosa
      surrounding the nasal polyp tissues or inferior turbinate tissues served as
      control (n=7). Immunohistochemical staining, reverse transcription polymerase
      chain reaction (RT-PCR), and Western blotting were performed for detecting the
      expression of survivin in the nasal polyps. RESULTS: This study has clearly shown
      that immunoreactivity of survivin significantly increased in the nasal polyp
      compared with nasal mucosa specimens surrounding nasal polyps (p<0.001). The
      higher expression of survivin Western blotting and RT-PCR also was observed in
      the nasal polyp but not in normal nasal mucosa. CONCLUSION: With a markedly
      increased expression of survivin in nasal polyps at both the mRNA and the protein
      levels, we believe the elevated expression of survivin might play an important
      role of development in nasal polyps.

PMID- 18336725
TI  - Allergic inflammation and adipocytokines.

PMID- 18336726
TI  - Autoimmunity and parasites.

PMID- 18336727
TI  - Recombinant allergens promote expression of aminopeptidase-n (CD13) on basophils
      in allergic patients.
AB  - IgE-dependent activation of basophils is associated with upregulation of several
      surface molecules. We recently identified the surface enzyme aminopeptidase N
      (CD13) as a novel activation antigen on human basophils. In the present study, we
      asked whether CD13 can be employed as a novel marker of allergen-induced
      activation of basophils in allergic individuals. Patients allergic to major
      allergens from grass pollen (Phl p 1, Phl p 5), birch pollen (Bet v 1), or house
      dust mites (Der p 2), were examined. Blood basophils were exposed to various
      concentrations of recombinant allergens for 15 minutes, and examined for
      expression of CD13 by multicolor flow cytometry. The allergen-induced
      upregulation of CD13 was compared with allergen-dependent increases in expression
      of CD63 and CD203c. Exposure to recombinant allergens resulted in an increase in
      expression of CD13 on basophils in all sensitized individuals, whereas no
      increase in CD13 was seen in healthy controls. The effects of the recombinant
      allergens on CD13-expression were dose- and time-dependent, were not observed in
      the absence of extracellular calcium, and were counteracted by preincubation of
      basophils with the PI3-kinase-targeting drugs staurosporin and LY294002. There
      was a good correlation between allergen-induced upregulation of CD13, CD63, and
      CD203c on basophils. In aggregate, our data show that recombinant allergens
      promote expression of CD13 on basophils in sensitized individuals. The functional
      significance and diagnostic implications of this observation remain to be
      determined.

PMID- 18336728
TI  - Expression and phosphorylation of protein kinase C isoforms in Abeta(1-42)
      activated T lymphocytes from Alzheimers disease.
AB  - The protein kinase C (PKC) family of enzymes is a regulator of transmembrane
      signal transduction. There is evidence demonstrating altered activity of some PKC
      isoforms (PKC-alpha, PKC-delta and PKC-zeta) in the neurons of brains of
      Alzheimers Disease (AD) sufferers, but little is known about their involvement in
      the intracellular machinery of amyloid beta protein-reactive T lymphocytes in AD.
      By applying a modified, split-well culture system, for Abeta(1-42) reactivity, we
      carried out flow cytometry analysis and biochemical investigations on the
      possible involvement of PKC-alpha, PKC-delta and PKC-zeta in the signalling
      system activated in Abeta-reactive T cells purified from peripheral blood
      mononucleate cells (PBMC) from healthy subjects and patients with AD. Flow
      cytometry analysis of Abeta(1-42) activated T lymphocytes in the majority of AD
      patients highlighted a distinct cellular cluster highly expressing phospho-PKC
      delta (P-PKC-delta), while most full-blown AD patients highly expressed two
      distinct P-PKC-delta and phospho-PKC-zeta (P-PKC-zeta) bright sub-populations.
      The same investigation performed in freshly purified peripheral T lymphocytes,
      did not highlight any subpopulation, suggesting that the detection of P-PKC-delta
      and P-PKC-zeta bright subpopulations is specifically linked to Abeta(1-42)
      activated T lymphocytes. The data presented here, therefore, suggest possible
      novel hallmarks to discriminate between healthy elderly subjects and beginning or
      full-blown Alzheimers Disease patients.

PMID- 18336729
TI  - Pulmonary exposure to carbon black nanoparticles increases the number of antigen
      presenting cells in murine lung.
AB  - Particulate matters can enhance antigen-related airway inflammation and
      immunoglobulin production. The present study was designed to determine the
      effects of different sizes of nanoparticles on the antigen-presenting cells (APC)
      in the lung. ICR mice were exposed to vehicle, carbon black (CB) nanoparticles
      (14 nm or 56 nm), ovalbumin (OVA), or OVA + nanoparticles intratracheally. The
      expression of major histocompatibility complex (MHC) class II, costimulatory
      molecules (CD80, CD86, CD11c), and DEC205 (dendritic cell marker), F4/80
      (macrophage marker), and CD19 (B-cell marker) in the lung cells was measured by
      flow cytometry. 14 nm nanoparticles, but not 56 nm nanoparticles, increased the
      number of the total lung cells. Combination of OVA and 14 nm or 56 nm
      nanoparticles increased the total lung cells. The expression of MHC class II
      and/or costimulatory molecules and the number of APC in the lung were increased
      by 14 nm nanoparticles in the presence or absence of OVA. The increases were more
      prominent with combination of OVA and 14 nm nanoparticles. 56 nm nanoparticles
      did not show any significant effects. 14 nm CB nanoparticles can increase the
      expression of MHC class II and costimulatory molecules and the number of APC in
      the lung, especially in the presence of antigen, which can result in subsequent
      antigen-related airway inflammation and immunoglobulin production.

PMID- 18336730
TI  - Evaluation of neutrophil CD64 expression and procalcitonin as useful markers in
      early diagnosis of sepsis.
AB  - Quantitation of neutrophil CD64 expression and procalcitonin (PCT) levels in
      blood samples have been recently proposed as useful tools for early detection of
      sepsis. To determine the usefulness of these tests, we analyzed blood samples of
      112 patients, admitted to an intensive care unit (ICU), presenting clinical
      symptoms of sepsis, as well as of 50 healthy controls. At the end of the study, a
      retrospective analysis showed that only 52 of the 112 ICU-patients presented a
      real sepsis (positive blood culture). The results obtained indicated that of the
      52 patients with sepsis, 50 and 49 presented levels of neutrophil CD64 expression
      >or= 2398 molecules per cell (cut-off determined by receiver operator
      characteristic analysis) and PCT levels >0.5 ng/ml (cut-off suggested by the
      manufacturer), respectively. However, the neutrophil CD64 test showed higher
      specificity in detecting sepsis since 5 out of the 60 ICU-patients without sepsis
      (negative blood culture), presented CD64 expression levels >or= 2398 molecules
      per cell, PCT levels >or= 0.5 ng/ml were shown in 27 patients. Moreover, while
      none of the 50 healthy controls presented a neutrophil CD64 level higher than the
      cut-off value, 5 patients presented PCT levels >or= 0.5 ng/ml. In conclusion, our
      data seem to indicate that the quantitation of CD64 expression could be taken
      into consideration as a sensitive and specific test for early diagnosis of
      sepsis.

PMID- 18336731
TI  - Bovine lactoferrin inhibits the efficiency of invasion of respiratory A549 cells
      of different iron-regulated morphological forms of Pseudomonas aeruginosa and
      Burkholderia cenocepacia.
AB  - Pseudomonas aeruginosa and Burkholderia cenocepacia are two important
      opportunistic respiratory pathogens of cystic fibrosis (CF) patients. Infections
      caused by these microorganisms are particularly difficult to eradicate because
      they are usually highly resistant to several currently available broad-spectrum
      antibiotics. Lactoferrin (Lf), a glycoprotein found in physiological fluids of
      mammals and present at high concentrations in infected and inflamed tissues,
      plays an important role in the natural defence mechanism against pathogens and in
      immune regulation. In the present study, we evaluate the ability of bovine
      lactoferrin (bLf) to influence P. aeruginosa PAO1 and B. cenocepacia PV1
      adhesiveness and invasiveness, using the A549 human bronchial cell line. Three
      different iron-induced morphological forms of bacteria (free-living, aggregates
      and biofilm) were assayed. The addition of bLf to cells just before infection had
      little influence on adhesion efficiency for all three of the morphological forms
      of B. cenocepacia PV1, while a slight increase in adhesion efficiency by P.
      aeruginosa PAO1 was noticed. Conversely, invasion of all three morphological
      forms of both P. aeruginosa and B. cenocepacia was strongly inhibited by the
      presence of bLf, independently of its degree of iron-binding activity. This is
      the first report demonstrating an anti-invasive property of bLf for strains of P.
      aeruginosa and B. cenocepacia.

PMID- 18336732
TI  - Periodate oxidized ATP (oATP) reduces hyperalgesia in mice: involvement of P2X7
      receptors and implications for therapy.
AB  - Some inflammatory mediators play an important role not only in the pathogenesis
      of the inflammatory pain, but also in that of neuropathic and visceral pain. We
      previously showed the antihyperalgesic effect of oATP, the inhibitor of the P2X7
      receptors for the pro-nociceptive ATP, in experimental inflammation. Here we show
      the antihyperalgesic effect of oATP in mouse models of neuropathic and visceral
      pain, other than in a model of arthritic pain mimicking rheumatoid arthritis in
      humans. We also show that mice lacking P2X7 receptors (KO) are resistant to
      hyperalgesic thermal stimuli following the induction of arthritic, neuropathic
      and visceral pain. Local (injection into the right hind paw) pre-treatment with
      oATP is able to prevent the successive induction of ATP-dependent hyperalgesia in
      wild type mice. In addition, KO mice are not insensitive to intraplantar
      treatment with ATP. Our data suggest that, even if oATP is able to inhibit
      purinoceptors different from P2X7, the latter are the more important involved in
      pain transmission.

PMID- 18336733
TI  - Omeprazole induces apoptosis in normal human polymorphonuclear leucocytes.
AB  - We investigated in vitro apoptosis in human polymorphonuclear neutrophils (PMN)
      induced by omeprazole. This drug, both in the native (OM) and acidified (OM-HCl)
      form, is a potent inducer of PMN apoptosis. The effect is time- and dose
      dependent. OM-HCl is more efficient than OM in inducing PMN apoptosis. In fact,
      after 24 h incubation in vitro at 1 x 10(-4) M OM-HCl induces apoptosis in 70% of
      the cell population compared to 37% induced by OM. Apoptosis induced by both
      forms of the drug is caspase dependent being significantly reduced by pretreating
      cells with the caspase 3 inhibitor (DEVDH-CHO). However, some differences in the
      apoptosis mechanisms between the two forms of the drug seem to exist because PMN
      treatment with the specific caspase 8 inhibitor (Z-IETD-FMK) only blocks OM-HCl
      mediated apoptosis. We observed cleavage of caspase 8 only in the cells incubated
      with OM-HCl while the executioner caspase 3 was activated with both forms of the
      drug. Furthermore, pretreatment with GM-CSF, a known activator of intracellular
      survival pathways in PMN, partially protected cells from OM-HCl induced apoptosis
      but did not contrast the apoptotic effect of OM. Cysteine cathepsin proteases
      also seem involved in the apoptotic mechanism of both drug forms since the
      specific inhibitor E64d gave a significant protection. To verify if OM-HCl
      induced apoptosis was dependent on the sulfenamide bound with the cell sulfhydryl
      groups we used molecules with thiol groups such as beta-mercaptoethanol (beta-ME)
      and reduced glutathione (GSH). Reactions of OM-HCl with cellular sulfhydryl
      groups are strongly involved in both the triggering and evolving phase of the
      apoptotic mechanism since significant protection from apoptosis was obtained when
      PMN were pretreated for 1 h with beta-ME (lipid-permeable) or GSH (lipid
      impermeable). These results show that OM and OM-HCl induce apoptosis in human PMN
      and suggest that the second binds the sulfhydryl groups, present on the cell
      membrane, to then penetrate the cell thus causing a further significant increase
      in apoptosis. OM-induced PMN apoptosis during the treatment of gastric
      inflammatory disease could be an advantage for the resolution of the phlogosis
      state. However, this aspect should be further elucidated to assess the optimal
      therapeutical regimen for gastric diseases which are related to infective agents.

PMID- 18336734
TI  - Modified arabinoxylan rice bran (MGN3/Biobran) enhances intracellular killing of
      microbes by human phagocytic cells in vitro.
AB  - Phagocytic cells, comprised of neutrophils and monocytes/macrophages, play a key
      role in the innate immune response to infection. Our earlier study demonstrated
      that arabinoxylan rice bran (MGN-3/Biobran) activates murine peritoneal
      macrophage and macrophage cell lines. In this study, we investigated whether MGN
      3 can upregulate the phagocytic activity of human phagocytes in peripheral blood
      to phagocytize Escherichia coli (E. coli), trigger the oxidative burst and
      produce cytokines. Phagocytic cells were pre-labeled with dichlorofluorescin
      diacetate dye and were incubated with phycoerythrin-labeled E. coli in the
      presence or absence of MGN-3. Phagocytosis and oxidative burst were assessed by
      flow cytometry. Results showed that treatment with MGN-3 enhanced the
      phagocytosis of E. coli by neutrophils and monocytes. This was associated with an
      increased oxidative burst. In addition, it caused a significant induction of
      cytokines (TNF-alpha, IL-6, IL-8 and IL-10); the effect was detected at 1
      microg/ml and increased in a dose-dependent manner (P <or= 0.01). Notably, MGN-3
      alone had no effect on the growth of 31 strains of bacteria suggesting that MGN-3
      modulates phagocytic cellular function. These findings may have applications in
      the treatment of infections in the elderly and in immunocompromised patients.

PMID- 18336735
TI  - Expression of CD38 in human neuroblastoma SH-SY5Y cells.
AB  - Human CD38 antigen is a 42-45 kDa type II transmembrane glycoprotein with a short
      N-terminal cytoplasmic domain and a long C-terminal extracellular region. It is
      widely expressed in different cell types including thymocytes, activated T cells,
      and terminally differentiated B cells (plasma cells) and it is involved in
      cellular proliferation and adhesion. CD38 acts as an ectocyclase that converts
      NAD+ to the Ca2+ -releasing second messenger cyclic ADP-ribose (cADPR). It has
      been also demonstrated that increased extracellular levels of NAD+ and cADPR are
      involved in inflammatory diseases and in cellular damage, such as ischemia. In
      the present study, we have characterized the expression of CD38 in human
      neuroblastoma SH-SY5Y cell line. All-trans-retinoic acid (ATRA) treatment was
      used to induce cell differentiation. Our results indicate that: a) even if SH
      SY5Y cells have a negative phenotype express CD38 at nuclear level, ATRA
      treatment does not influence this pattern; b) CD38 localizing to the nucleus may
      co-localize with p80-coilin positive nuclear-coiled bodies; c) purified nuclei,
      by Western blot determinations using anti-CD38 antibodies, display a band with a
      molecular mass of approximately 42 kDa; d) SH-SY5Y cells show nuclear ADP-ribosyl
      cyclase due to CD38 activity; e) the basal level of CD38 mRNA shows a time
      dependent increase after treatment with ATRA. These results suggest that the
      presence of constitutive fully functional CD38 in the SH-SY5Y nucleus has some
      important implications for intracellular generation of cADP-ribose and subsequent
      nucleoplasmic calcium release.

PMID- 18336736
TI  - How do rat cortical cells cultured with aluminum die: necrosis or apoptosis?
AB  - Aluminum (Al) exposure has been implicated as the cause of neural cells loss in
      several neurodegenerative diseases. Therefore, defining the mechanism of neural
      cell death in Al toxicity and degenerative diseases might lead to the development
      of therapeutic agents which promote neural cell survival. Furthermore, knowledge
      of cell death pathways might facilitate the discovery of treatments for
      neurodegeneration. However, the death mode of neural cells triggered by Al has
      not been firmly established. The present study focuses on understanding the
      pathway of cells death in cultured cortical cells treated with Al. Primary
      neurons cultured alone, astrocytes cultured alone, and neuron/astrocyte co
      cultures obtained from newborn rats were incubated with Al at the concentrations
      of 0, 0.5, 1.0, or 2.0 mM for 72 h. Morphological changes were observed with an
      inverted phase microscope, a fluorescent microscope, and an electron microscope.
      Simultaneously, the rate of apoptosis was quantified with flow cytometry.
      Morphological characteristics of apoptosis such as cell shrinkage, aggregation
      and fragmentation of chromatin, membrane buds, and formation of membrane-bound
      apoptotic bodies were observed in Al-treated neurons, while none of these
      characteristics were found in Al-treated astrocytes. Quantitative results of
      apoptotic rates detected with flow cytometry indicated a typical apoptosis
      progression in neurons at various dosages. A concentration-dependent relationship
      between Al concentration and apoptotic rates confirmed that apoptosis is the
      prominent cause of cell death in primary cultured neurons, even at a
      concentration lower than 2 mM. Both necrosis and apoptosis are evident in
      neuron/astrocyte co-cultures, but the intensity of apoptosis is much less
      compared with that of neurons, suggesting that astrocytes may be especially
      important for neuronal survival in the presence of Al.

PMID- 18336737
TI  - Visiting a forest, but not a city, increases human natural killer activity and
      expression of anti-cancer proteins.
AB  - We previously reported that a forest bathing trip enhanced human NK activity,
      number of NK cells, and intracellular anti-cancer proteins in lymphocytes. In the
      present study, we investigated how long the increased NK activity lasts and
      compared the effect of a forest bathing trip on NK activity with a trip to places
      in a city without forests. Twelve healthy male subjects, age 35-56 years, were
      selected with informed consent. The subjects experienced a three-day/two-night
      trip to forest fields and to a city, in which activity levels during both trips
      were matched. On day 1, subjects walked for two hours in the afternoon in a
      forest field; and on day 2, they walked for two hours in the morning and
      afternoon, respectively, in two different forest fields; and on day 3, the
      subjects finished the trip and returned to Tokyo after drawing blood samples and
      completing the questionnaire. Blood and urine were sampled on the second and
      third days during the trips, and on days 7 and 30 after the trip, and NK
      activity, numbers of NK and T cells, and granulysin, perforin, and granzymes A/B
      expressing lymphocytes in the blood samples, and the concentration of adrenaline
      in urine were measured. Similar measurements were made before the trips on a
      normal working day as the control. Phytoncide concentrations in forest and city
      air were measured. The forest bathing trip significantly increased NK activity
      and the numbers of NK, perforin, granulysin, and granzyme A/B-expressing cells
      and significantly decreased the concentration of adrenaline in urine. The
      increased NK activity lasted for more than 7 days after the trip. In contrast, a
      city tourist visit did not increase NK activity, numbers of NK cells, nor the
      expression of selected intracellular anti-cancer proteins, and did not decrease
      the concentration of adrenaline in urine. Phytoncides, such as alpha-pinene and
      beta-pinene were detected in forest air, but almost not in city air. These
      findings indicate that a forest bathing trip increased NK activity, number of NK
      cells, and levels of intracellular anti-cancer proteins, and that this effect
      lasted at least 7 days after the trip. Phytoncides released from trees and
      decreased stress hormone may partially contribute to the increased NK activity.

PMID- 18336738
TI  - Activity and expression of nitric oxide synthase in rat bladder after sacral
      neuromodulation.
AB  - The aim of our study is to investigate the effects of chronic sacral
      neuromodulation on Nitric Oxide (NO) metabolism in the rat bladder. 26 female
      Sprangue-Dawley rats were considered: group I, normal control rats; group II, a
      sham treatment, in whom catheters for electrical stimulation were placed in the
      S1 foramen bilaterally and left in place for 21 days, without performing
      neuromodulation; group III in whom electrical sacral neuromodulation was
      performed for 21 days. Finally a cystectomy was performed and the bladder biopsy
      specimens were sent for immunostaining with n-NOS and i-NOS. Morphological and
      immunohistochemical analysis was carried out, and evaluated in urothelial cells,
      endothelial cells and muscle fibers of the muscularis propria. Differences
      between the 3 groups were analyzed by Student Newman-Keuls test. We could observe
      that urothelial and endothelial i-NOS (37.00+/-4.69 and 59.00+/-7.42
      respectively) and urothelial n-NOS (36.80+/-7.85) expression are significantly
      increased in neuromodulated rats, compared to groups 1 and 2 (p<0.005). In
      conclusion, the increase of i-NOS expression on endothelial cells after sacral
      neuromodulation could be in some way related to angiogenetic responses in the
      microvascular structures; the increase of n-NOS and i-NOS expression on
      urothelial cells can suggest that NO is able to influence the plasticity of
      bladder response, inducing the release of messengers within the urothelium. This
      study can therefore improve our understanding of the mechanisms of sacral
      neuromodulation on chronic bladder dysfunction; further studies will need to
      better demonstrate the role of angiogenesis in the bladder after sacral
      neuromodulation and to investigate the effects of neuromodulation in rats with
      chronically induced bladder dysfunction.

PMID- 18336739
TI  - Increase of skin-ceramide levels in aged subjects following a short-term topical
      application of bacterial sphingomyelinase from Streptococcus thermophilus.
AB  - Several studies have demonstrated that ceramides play an essential role in both
      the barrier and water-holding functions of healthy stratum corneum, suggesting
      that the dysfunction of the stratum corneum associated with ageing as well that
      observed in patients with several skin diseases could result from a ceramide
      deficiency. In a previous study our group reported a significant increase in skin
      ceramide levels in healthy subjects after treatment in vivo with a cream
      containing a preparation of Streptococcus thermophilus. The presence of high
      levels of neutral sphingomyelinase activity in this organism was responsible for
      the observed increase of stratum corneum ceramide levels, thus leading to an
      improvement in barrier function and maintenance of stratum corneum flexibility.
      The aim of the present work is to investigate the effects of the topical
      treatment of a Streptococcus thermophilus-containing cream on ceramide levels of
      stratum corneum of healthy elderly women. The ceramide levels, transepidermal
      water loss and capacitance were evaluated on stratum corneum sheets from the
      forearms of 20 healthy female subjects treated with a base cream or the same
      cream containing a sonicated preparation of the lactic acid bacterium
      Streptococcus thermophilus. A 2-week topical application of a sonicated
      Streptococcus thermophilus preparation led to significant and relevant increase
      of stratum corneum ceramide levels. Moreover, the hydration values of the treated
      forearm of each subject was significantly higher than control sites. These
      results suggest that the experimental cream was able to improve the lipid barrier
      and to increase a resistance against ageing-associated xerosis.

PMID- 18336740
TI  - Cutaneous human papillomaviruses as recurrence factor in actinic keratoses.
AB  - Actinic keratoses (AK) are common, premalignant lesions cause mainly by UV DNA
      damage. Progression into squamous cell carcinoma may be influenced by other
      several factors such as chronic chemical exposure or viral infection. A
      carcinogenic role of Human Papillomaviruses (HPV) in early steps of skin tumour
      development was recently hypothesized; moreover the presence of HPV DNA seems to
      be higher in cancer precursor lesions. The aim of this work is to identify the
      presence of HPV DNA in biopsies from Actinic Keratoses (AK) and from normal skin
      samples collected from dermatological healthy subjects in Italy, in order to
      evaluate the severity and the clinical evolution of the HPV positive lesions. The
      DNA test revealed 37% HPV positivity in AK patients versus 0% in the control
      group; many different genotypes and variants were identified by direct sequencing
      of PCR product. The HPV positive AK were usually clinically indistinguishable
      from the HPV negative. All AK lesions were removed by laser treatment, but AK
      lesions recurred in all HPV positive patients after a period of 45-60 days
      whereas the same disappeared in the HPV negative ones. These data permit to
      hypothesize that the presence of HPV DNA could be an aggravating factor for AK
      lesion severity and recurrence.

PMID- 18336741
TI  - Role of fosfomycin tromethamine in modulating non-specific defence mechanisms in
      chronic uremic patients towards ESBL-producing Escherichia coli.
AB  - Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to
      interact in such a way that improve the therapy for infectious diseases. In
      immunocompromised patients highly susceptible to microbial infections with high
      morbidity and mortality, several metabolic and functional alterations in PMNs,
      mostly related to microbicidal activity, are observed. Therefore, the antibiotic
      of choice should have a good antimicrobial effect without impairing host
      defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting
      fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from
      healthy subjects and immunocompromised patients (haemodialysed and renal
      transplant recipients), against an ESBL-producing Escherichia coli, the most
      common aetiological agent in urinary tract infections (UTIs). FT is considered a
      first line drug in the eradication of UTIs due to its appropriate antimicrobial
      spectrum, oral bioavailability and minimal risk of microbial resistance. Our
      results provide evidence that FT is able to induce enhancement of the depressed
      phagocytic response of PMNs from patients on chronic haemodialysis and from renal
      transplant recipients, restoring their primary functions in vitro against ESBL
      producing E. coli. All these data permit the conclusion that uremic-infected
      patients might additionally benefit from the immunomodulating properties of FT.

PMID- 18336742
TI  - Activation of interferon response genes and of plasmacytoid dendritic cells in
      HIV-1 positive subjects with GB virus C co-infection.
AB  - GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency
      Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia
      in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate
      antiviral response may be involved in the protection, we analyzed the possible
      role of GBV-C as activator of innate immunity. To this aim, we measured the
      extent of activation of the interferon (IFN) system and of circulating Dendritic
      Cells (DC) in vivo, and the ability of GBV-C to activate these functions in
      vitro. Activation of IFN system and of circulating DC was compared in GBV
      positive and -negative HIV-1 co-infected patients with HAART-driven suppression
      of HIV-1 viremia. Endogenous levels of IFN-gamma and RNA-dependent protein kinase
      (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC)
      from GBV-C-positive when compared to GBV-C-negative patients. IFN-gamma
      expression was correlated with all the Interferon response genes (IRGs) and with
      GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the
      CD80 activation marker was increased in GBV-C-positive patients, and was
      correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is
      able to induce IFN-gamma expression in PBMC. In addition, in PBMC cultures GBV-C
      induced an increase of CD80 expression by pDC, that was reduced by antibody to
      IFN-gamma. Our data indicate that in HIV-positive patients GBV-C coinfection
      promotes the activation of IFN-gamma and downstream IRG expression, as well as
      with the activation/maturation of circulating pDC. GBV-C-driven IFN-gamma
      activation is, at least in part, responsible for the increased maturation of pDC.
      This crosstalk may suggest a role for GBV-C coinfection in boosting the innate
      antiviral response to HIV infection.

PMID- 18336743
TI  - Epithelial lining fluid neutrophil-gelatinase-associated lipocalin levels in
      premature newborns with bronchopulmonary dysplasia and patency of ductus
      arteriosus.
AB  - Patency of the ductus arteriosus (PDA) and bronchopulmonary dysplasia (BPD)
      development represent severe affections for premature newborns, therefore the
      research of early markers for these two conditions is really important. The aim
      of this study is to analyze epithelial lining fluid (ELF) Neutrophil-gelatinase
      associated lipocalin (NGAL) levels for prediction of lung injury or possible
      involvement of this molecule in PDA. Only scarce and contrasting results have
      previously been published in this field. In contrast, this molecule, included in
      a large macromolecular complex together with matrix metalloproteinase-9 (MMP-9),
      is considered an acceptable marker of infectious/inflammatory processes, cancer
      monitoring and induction of apoptotic pathway. NGAL was detected in 28 pre-term
      newborns by means of a commercially available kit in bronchoalveolar lavage fluid
      (BALF). The results have been corrected to ELF levels, by the urea method, to
      eliminate bias due to BALF collection. ELF NGAL levels were found significantly
      increased both in infants developing BPD or in those affected by PDA. By means of
      multivariate logistic regression analysis the significances were confirmed after
      adjusting for possible interfering variables such as gestational age and
      concomitant presence of both PDA and BPD. Our results stress the involvement of
      NGAL in the mechanisms leading to BPD and also suggest a possible association
      with PDA, which is often linked to prematurity and BPD development, probably due
      to the involvement of inflammatory and angiogenetic processes in both
      pathologies.

PMID- 18336744
TI  - Intravitreal micronized triamcinolone versus triamcinolone acetonide: a clinical
      and morphological comparative study.
AB  - Nowadays many authors suggest the use of intravitreal triamcinolone acetonide
      (TA) for the treatment of vitreoretinal diseases, although it can be associated
      with a high risk of local toxicity. In order to develop a safer injection for
      clinical use, the purpose of our study is to evaluate the in situ safety of two
      different triamcinolone preparations, a commercially available TA and a
      micronized triamcinolone. The experiments were performed on 18 adult male age
      matched New Zealand rabbits. The clinical examination included funduscopy with an
      indirect ophthalmoscope and intraocular pressure (IOP) measurement. At the end of
      the clinical observations, the animals were sacrificed and the eyes enucleated
      and processed for the morphological evaluation. In our study the main side effect
      observed was the IOP elevation in the group injected with triamcinolone
      acetonide. In addition, in the TA-injected group, one eye was enucleated
      following an endophthalmitis. Our study highlights that doses as low as 4 mg of
      triamcinolone acetonide injected into the rabbit vitreous may have a local toxic
      effect in terms of IOP elevation, endophthalmitis occurrence and changes in the
      retinal morphology. In contrast, the micronized triamcinolone injection shows a
      less toxic effect in situ, thus suggesting the alternative use of this more
      reliable preparation which seems to be safer for a clinical use.

PMID- 18336745
TI  - At least three phosphorylation events induced by pemphigus vulgaris sera are
      pathogenically involved in keratinocyte acantholysis.
AB  - Intercellular adhesion among keratinocytes is guaranteed by desmosomes.
      Disruption of desmosomal integrity leads to cell-cell detachment or acantholysis,
      as it classically occurs in pemphigus vulgaris (PV), an autoimmune blistering
      disease of skin and mucous membranes. While purified PV IgG seems to trigger
      intracellular signaling that crucially involves p38 MAPK, keratinocyte
      acantholysis induced by whole PV serum may recruit a number of additional
      signals. In this study, the Pro-Q Diamond Phosphoprotein Assay was used to
      investigate the overall changes in protein phosphorylation levels in an in vitro
      model of PV. We showed that keratinocytes exposed to whole PV sera underwent at
      least three early and transient phosphorylation events. Two bands with apparent
      molecular masses of 35 and 45 kDa were found to be phosphorylated within 1 min
      after incubation with PV sera. A third band of about 80 kDa reached the peak of
      phosphorylation level after 3 hours. Morphologic evidence of cell shrinkage and
      acantholysis were late events and did not correlate temporally with kinase
      activation, suggesting that cytoskeleton reorganization is a downstream
      phenomenon. Interestingly, pharmacological abrogation of PV-specific protein
      phosphorylation was able to inhibit the cell-cell detachment, rounding up, and
      redistribution of Dsg3 in keratinocytes. Thus, at least three phosphorylation
      events are pathogenically involved in pemphigus acantholysis.

PMID- 18336746
TI  - Size effects of nanomaterials on lung inflammation and coagulatory disturbance.
AB  - Effects of nano-sized materials (nanomaterials) on subjects with predisposing
      inflammatory disorders have not been well elucidated. This study examined the
      effects of pulmonary exposure to TiO2 nanomaterials on lung inflammation induced
      by lipopolysaccharide (LPS) and consequent systemic inflammation with coagulatory
      disturbance in mice, in particular regarding their size-dependency. Also, gene
      expression pattern in the lung was compared among the experimental groups using
      cDNA microarray analysis. ICR male mice were divided into 8 experimental groups
      that intratracheally received vehicle, three sizes (15, 50, 100 nm) of TiO2
      nanomaterials (8 mg/kg), LPS (2.5 mg/kg), or LPS plus nanomaterials. Twenty four
      h after the treatment, these nanomaterials exacerbated the lung inflammation and
      vascular permeability elicited by LPS, with an overall trend of amplified lung
      expressions of cytokines such as interleukin (IL)-1beta, macrophage
      chemoattractant protein (MCP)-1, and keratinocyte chemoattractant (KC). LPS plus
      nanomaterials, especially of a size less than 50 nm, elevated circulatory levels
      of fibrinogen, IL-1beta, MCP-1, and KC, and von Willebrand factor as compared
      with LPS alone. The enhancement tended overall to be greater with the smaller
      nanomaterials than with the larger ones. cDNA microarray analyses revealed that
      there was no difference in gene expression pattern between the LPS group and the
      LPS + nanomaterial. These results suggest that nanomaterials exacerbate lung
      inflammation related to LPS with systemic inflammation and coagulatory
      disturbance, and that the exacerbation is more prominent with smaller
      nanomaterials than with larger ones.

PMID- 18336747
TI  - Impact of different texture of polypropylene mesh on the inflammatory response.
AB  - Over the past decade, hernia surgery has undergone a considerable transformation
      with the use of prosthetic materials. The most used polypropylene meshes induce a
      rapid acute inflammatory response followed by chronic foreign body reaction. Many
      factors influence this response such as density, size, physical characteristics,
      different texture and porosity of each biomaterial. The aim of this study is to
      assess whether the implant of monofilament or multifilament meshes, in the
      inguinal hernioplasty, determine a different inflammatory response. Thirty-two
      male patients were included in the study and were randomly divided into two
      groups. In the first group (MO) inguinal hernioplasty was performed using
      monofilament polypropylene mesh, while in the second one (MU) multifilament
      prosthesis was used. Peripheral venous blood samples were collected 24 hours
      before surgery and then 6, 24, 48 and 168 hours post-operatively. Modifications
      in leukocyte count, C-reactive protein (CRP), alpha-1 antitrypsin (alpha1-AT),
      interleukin (IL)-1, IL-6, IL-1 ra and IL-10 serum levels were recorded at all
      sampling times. We present evidence that serum levels of CRP, (alpha1-AT),
      leukocytes and cytokines were significantly increased post-operatively in both
      groups, returning to basal values 168 hours afterwards. In particular, the
      production of all pro-inflammatory mediators was higher in the MU group, whereas
      the anti-inflammatory cytokine (IL-10, IL-1ra) production was higher in MO
      patients. Our results indicate that polypropylene multifilament mesh allows a
      higher intense acute inflammatory response as compared to monofilament mesh
      implantation.

PMID- 18336748
TI  - Bronchiectasis in children with recurrent pneumonia: an immunopathological damage
      associated with secondary ciliary dysmotility.
AB  - The aim of this study is to assess ciliary motion patterns in children with
      bronchiectasis unrelated to cystic fibrosis or primary ciliary dyskinesia. In 51
      children with recurrent pneumonia, high resolution computed tomography (HRCT) was
      carried out to detect and score bronchiectasis. Moreover, ciliary ultrastructure,
      beat frequency and motion pattern were evaluated and compared to those observed
      in 30 healthy children. Bronchiectasis at HRCT was found in 31/51 children.
      Ciliary dysmotility was found in 20/31 children with bronchiectasis (64.5%).
      Overall, ciliary dysmotility was found in 39/51 patients (76.5%). Ciliary
      dysmotility showed a significant correlation with the HRCT score (p=0.02). Absent
      motion in some fields was found in 44/51 patients (86.3%) and this also showed
      significant correlation with the HRCT score (p=0.005). The specificity and
      sensitivity of ciliary dysmotility as an indicator of bronchiectasis was 74.3%
      and 83.3% respectively. The positive predictive value was 93.5%, and negative
      predictive value was 50%. Ciliary dysmotility, in children with recurrent airways
      infections, correlates with the presence and severity of bronchiectasis. Whether
      ciliary dysmotility is a cause or a consequence of anatomical lesion is a matter
      of speculation. Very likely there is an amplification and self-maintaining
      mechanism between the two events which may lead to more serious disease.

PMID- 18336749
TI  - Effects of the hormones of the thyroid axis on the vitamin K-dependent plasma
      factors of blood coagulation (II, VII, IX, and X).
AB  - The hormonal regulation of haemostasis is a problem which has not received much
      attention. The data concerning the influence of hormones from the hypothalamic
      pituitary-thyroid axis are scarce, contradictory and based mainly on clinical
      observations. The objective of the current research is to study the influence of
      the Thyrotropin releasing hormone (TRH), Thyroid stimulating hormone (TSH),
      Triiodothyronine (T3) and Thyroxin (T4) on the activity level of the vitamin K
      dependent plasma factors of blood coagulation--factor II (F II), factor VII (F
      VII), factor IX (F IX) and factor X (F X). This study was carried out on 40 male
      Wistar rats. The necessary quantity of blood was obtained by cardiac puncture
      under ether narcosis. The indicators studied were activated partial
      thromboplastin time (aPTT), protothrombin time (PT), F II, F VII, F IX and F X,
      and were determined by means of Diagnostica Stago tests and with the help of an
      automatic coagulometer. The hormones studied were: TRH (0.06 mg/kg b.w.), TSH (1
      MU/kg b.w.), T3 (0.08 mg/kg b.w.) T4 (0.08 mg/kg b.w.) prolonged aPTT (p<0.001)
      and PT (p<0.001). TRH and T3 significantly reduced the activity level of factors
      II, VII, IX and X; T4 only reduced the level of F II (p<0.05), and TSH did not
      induce significant changes in the haemocoagulation factors studied. The TRH, TSH,
      T3 and T4 hormones, although elements of one and the same axis, have an ambiguous
      effect on the vitamin K-dependent factors of blood coagulation. The results
      obtained show that the determined changes in the activity levels of the vitamin K
      dependent plasma factors of blood coagulation are undoubtedly related to the
      hypocoagulation observed in the intrinsic and extrinsic pathways under the
      influence of the hormones of the thyroid axis.

PMID- 18336750
TI  - Intratumoral vs systemic administration of meta-tetrahydroxyphenylchlorin for
      photodynamic therapy of malignant gliomas: assessment of uptake and spatial
      distribution in C6 rat glioma model.
AB  - Malignant gliomas, with an incidence of 5 cases per 100,000 population per year,
      represent the most common primary brain tumour. They have an overall survival
      length of less than 2 years. Many different adjuvant therapies have been
      developed. Among them, Photodynamic Therapy (PDT), that is based on photochemical
      reactions between light and tumoral tissue selectively labelled with exogenous
      photosensitizing agents. Among photosensitizers, m-THPC (Temoporfin), seems to be
      the most promising one for the treatment of brain tumors, but, unfortunately, it
      causes problems of high skin photosensitivity. To by-pass this problem, we
      devised an intratumoral route of administration of this photosensitizer. The aim
      of this study is to investigate and compare the uptake of m-THPC in brain tumor
      and normal tissue after systemic and intratumoral administration of the drug. 30
      female Wistar rats received m-THPC 12 days after C6 tumor implantation.
      Temoporfin was administered intratumorally in 24 rats at two different
      concentrations. 6 rats constituted the control group and received m-THPC by means
      of an intraperitoneal injection. The brains were extracted at 4 h, 24 h and 96 h
      after Temoporfin injection. The samples were examined with a confocal laser
      scanning microscope. All samples showed high fluorescence emission exclusively in
      the tumour area, without appreciable differences between the samples taken at the
      different times of sacrifice and the two routes of administration. No
      fluorescence whatsoever was detected among normal brain tissue surrounding the
      tumour. The intratumoral route appears to give comparable results to the systemic
      one, regarding intracellular uptake efficiency and tumour--normal tissue ratio,
      with the advantage of a much shorter time needed to reach optimal intratumoural
      concentration--that is just four hours from m-THPC injection.

PMID- 18336751
TI  - Parecoxib as an alternative in COX-2 hypersensitivity.
AB  - The group of non-steroidal anti-inflammatory drugs (NSAIDs) is commonly involved
      in hypersensitivity reactions. In clinical practice the physician is often faced
      with the need to choose an alternative anti-inflammatory agent for a patient who
      has suffered a hypersensitivity reaction to a NSAID. The most common approach to
      choosing the safest NSAID is to perform a challenge test. Parecoxib is the first
      injectable COX-2 selective inhibitor indicated for the treatment of acute
      postoperative pain. The authors report the case of a patient with a history of
      cutaneous adverse reactions to different classes of NSAIDs, including selective
      COX-2 inhibitors, who underwent and tolerated challenge with parecoxib.

PMID- 18336752
TI  - Dilated cardiomyopathy due to thrombotic microangiopathy as the only
      manifestation of antiphospholipid syndrome: a case report.
AB  - Dilated cardiomyopathy due to thrombotic microangiopathy has been rarely reported
      as a clinical manifestation of antiphospholipid syndrome (APS). We describe the
      case of a 39-year-old woman affected by systemic lupus erythematosus (SLE) and
      positive antiphospholipid antibodies (aPL) who presented with orthopnea and
      peripheral oedema. Diagnosis of dilated cardiomyopathy due to myocardial
      thrombotic microangiopathy was made and treatment with anticoagulants prevented
      the worsening of the clinical condition. Interestingly, at variance with other
      cases, our patient showed no extracardiac signs of APS. The review of the current
      literature has confirmed that dilated cardiomyopathy due to thrombotic
      microangiopathy is a rare manifestation of APS.

PMID- 18336753
TI  - Sinus augmentation procedure of the jaw sinus in patients with mucocele.
AB  - The sinus augmentation procedure of the jaw sinus (SAP) is a surgical technique
      which permits the prosthetic rehabilitation of the edentulous saddles by the
      insertion of dental implants where unfavourable conditions exist for their
      application. Nevertheless, apart from malignant tumors, benign pathologies exist,
      such as mucocele or radicular cysts, which can complicate the SAP, causing
      sinusal disturbances. In this study we describe our experience of SAP in patients
      with mucocele of the jaw sinus, and describe our surgical technique without the
      preventive emptying of the mucocele. Based on our experience, the SAP operation
      can be carried out without complications if the distance between the top of the
      mucocele with SAP and the osteomeatal complex (OMC) is 22 mm, or for mucocele no
      larger than 18 mm. In fact, these parameters guarantee that, because of the
      lifting of the sinusal membrane, the antral drainage (AD) duct does not alter or
      become obstructed.

PMID- 18336754
TI  - Recurrent venous thromboembolism complicated by heparin-induced thrombocytopenia
      as a first manifestation of an occult cancer: a case report.
AB  - Heparin-Induced Thrombocytopenia (HIT) is a serious and potentially fatal
      complication of patients on heparins. Its management is difficult and it can be
      more complicated in patients with cancer because of the hemorrhagic risk carried
      out by direct inhibitor of thrombin, the currently approved drug for HIT. At
      present, it is not clear whether cancer patients also have an increased risk of
      HIT. We describe the case of a patient with occult cancer at the moment of the
      index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant
      HIT with thrombotic complications (recurrent contra-lateral venous thrombosis).
      The management of HIT was efficaciously based on the combined use of alternative
      antithrombotic regimens (Dermatan-Sulphate and Defibrotide), without an increased
      risk of bleeding. This case highlights the potential relationship between DVT, as
      first episode of an occult cancer, and the risk of developing HIT. The use of
      alternative antithrombotic therapy seems to be efficacious even in this high-risk
      cancer patient.

PMID- 18336755
TI  - Hypoxemia with high alveolar-arterial oxygen gradient but no lung involvement in
      a patient with Churg-Strauss syndrome: case report.
AB  - Churg-Strauss syndrome (CSS) is characterized by asthma and/or a history of
      allergy, eosinophilia and an often life-threatening systemic necrotizing
      vasculitis. We describe a patient with CSS and hypoxemia with a high alveolar
      arterial oxygen gradient (AaDO2), but no pulmonary parenchymal involvement. The
      patient also had a low diffusion capacity with normal lung volume and a high
      level of serum thrombomodulin, a marker of endothelial cell injury. Treatment for
      CSS, such as corticosteroid, improved both hypoxemia and AaDO2 consistent with
      amelioration of diffusion capacity and serum thrombomodulin level, suggesting
      that this pathosis involves microangiopathy with endothelial cell damage induced
      by vasculitis in pulmonary blood vessels.

PMID- 18336756
TI  - [Emphasis on the research of sleep apnea pattern intermittent hypoxia].

PMID- 18336757
TI  - [To further study the pathogenesis of obstructive sleep apnea-hypopnea syndrome].

PMID- 18336758
TI  - [The relationship between obstructive sleep apnea hypopnea syndrome and
      cerebrovascular diseases].

PMID- 18336760
TI  - [The clinical recognition and simple diagnostic procedures for obstructive sleep
      apnea and hypopnea syndrome].

PMID- 18336761
TI  - [Continuous positive airway pressure treatment for obstructive sleep apnea
      hypopnea syndrome].

PMID- 18336762
TI  - [Obstructive sleep apnea hypopnea and metabolic syndromes].

PMID- 18336763
TI  - [A multi-center study on the association between sleep apnea and prevalence of
      hypertension].
AB  - OBJECTIVE: To investigate the prevalence of hypertension among sleep apnea
      patients and the associated factors. METHODS: A total of 2297 patients (male
      1310, female 211) from 20 teaching hospitals were enrolled in this study. Medical
      history interview, blood pressure measurement and an in-hospital polysomnogram
      were performed for all the patients. Questionnaires of sleep apnea and
      hypertension were finished by all the patients. SPSS 11.0 software package was
      used for data analyzing, and prevalence rates of hypertension were compared by
      chi-square test. RESULTS: The prevalence of hypertension in the apnea hypopnea
      index (AHI) < 5/h group was 23.5%, but in AHI > or = 5/h group was 49.3%, the
      difference being significant. The prevalence of hypertension in the group with
      obstructive sleep apnea hypopnea syndrome (OSAHS) was 56.2%, but was 63.7% and
      39.4% in the groups with and without hypertension family history, respectively.
      The odds ratio of hypertension in AHI > or = 5/h group was 3.167 times higher
      than in the AHI < 5/h group (OR = 3.167, 95% CI 2.953 - 5.426, P < 0.01). The
      prevalence of hypertension increased with AHI increases, and it was the highest
      in subjects with AHI of 16 - 20/h, but deceased slowly in subjects with AHI of 66
      - 70/h. Two equations were formulated to show the relationship between AHI and
      the prevalence of hypertension: the prevalence of hypertension = 0.3199 + 0.0042
      x AHI, and OR of the prevalence of hypertension = 1.018 + 0.017 x AHI. The AHI
      was an independent risk factor for the prevalence of hypertension after control
      for age, sex, BMI and family history of hypertension. CONCLUSIONS: The prevalence
      of hypertension in subjects with sleep apnea was higher than those without sleep
      apnea. There was a close relationship between sleep apnea syndrome and the
      prevalence of hypertension. Sleep apnea was an independent factor for
      hypertension after control for the confounding factors.

PMID- 18336764
TI  - [The effect of chronic intermittent hypoxia caused by obstructive sleep apnea
      hypopnea syndrome on blood pressure].
AB  - OBJECTIVE: To explore the effect of chronic intermittent hypoxia caused by
      obstructive sleep apnea hypopnea syndrome (OSAHS) and chronic continuous hypoxia
      caused by chronic obstructive pulmonary disease (COPD) on blood pressure and
      levels of nitric oxide (NO)/endothelin (ET). METHODS: A total of 85 cases were
      selected, including OSAHS patients over 18 years old visited this hospital from
      June to August 2006, stable COPD patients and healthy volunteers. According to
      the results of clinical questionnaire, pulmonary function test and polysomography
      (PSG), they were divided into 4 groups: non-smoking OSAHS patients (n = 26),
      smoking OSAHS patients (n = 22), patients with stable COPD (n = 17) and healthy
      control subjects (n = 20). Blood pressure measurement was performed before and
      after the PSG examination while the subjects were resting. The levels of ET and
      NO in blood samples and exhaled breath condensates (EBC) were measured by
      radioimmunoassay and nitrate reductase, respectively. Measurement data were
      analyzed by ANOVA, numeration data were analyzed by chi-square test, data of
      normal distribution were analyzed by Pearson correlation analysis, and non-normal
      data were analyzed by Spearman correlation analysis. Multiple linear regression
      analysis was also performed. RESULTS: Regardless of the smoking status, the
      difference of morning-evening diastolic blood pressure (DBP) in the morning of
      patients with OSAHS [non-smoking OSAHS: (88 +/- 10) mm Hg, 1 mm Hg = 0.133 kPa;
      smoking OSAHS: (95 +/- 17) mm Hg] was higher than that of patients with COPD [(76
      +/- 7) mm Hg] and healthy subjects [(70 +/- 6) mm Hg]. The difference of morning
      evening NO level in EBC of patients with OSAHS [non-smoking OSAHS: (-4.5 +/- 7.9)
      micromol/L; smoking OSAHS: (-3.4 +/- 5.5) micromol/L] was lower than that of
      patients with COPD [(1.4 +/- 6.1) micromol/L] and healthy subjects [(3.1 +/- 4.0)
      micromol/L]. The ratio of NO to ET in serum of the smoking OSAHS group (1.0 +/-
      0.5) was lower than that of the COPD group (1.4 +/- 0.7). After adjustment for
      sex, age, BMI, waist circumference, history of smoking and alcohol, level of
      hypertension, and category of antihypertensive drugs, the morning-evening
      difference of NO level in EBC was negatively associated with the morning-evening
      difference of DBP (r = -0.301, P = 0.021), and was positively associated with
      apnea hypopnea index (AHI) (r = 0.116, P < 0.05). The morning-evening difference
      of DBP was associated with AHI (r = -0.303, P = 0.011), amplitude of oxygen
      desaturation with pulse oxygen saturation (SpO(2)) less than 90% (OLA90%, r = 
      0.281, P = 0.018), and gradient of oxygen desaturation with SpO(2) less than 90%
      (OLG90%, r = 0.286, P = 0.035). Multiple linear regression analysis showed that,
      if AHI increased by 1/h, the morning-evening difference of DBP would increase
      0.41 mm Hg; if the morning-evening difference of NO level in EBC increased by 1
      micromol/L, the morning-evening difference of DBP would decrease 0.27 mm Hg; and
      if AHI increased by 1/h, the morning-evening difference of NO level in EBC would
      increase 0.40 micromol/L. CONCLUSION: The DBP of OSAHS patients in the morning is
      significantly higher than that in the evening. The morning-evening difference of
      NO level in EBC reflects indirectly the consumption of NO in the body, and is
      associated with the degree of OSAHS and the morning-evening difference of DBP.

PMID- 18336765
TI  - [The effect of percutaneous transluminal stenting for vertebrobasilar ischemia on
      sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To evaluate the relationship between vertebrobasilar ischemia (VBI)
      and sleep apnea hypopnea syndrome (SAHS) and the effect of percutaneous
      transluminal stenting for VBI on the clinical parameters of SAHS. METHODS: Twenty
      patients with VBI were included for clinical history, physical examination with
      sleep quentionnaires and scored by the Epworth Sleepiness Scale (ESS).
      Polysomnographic (PSG) studies were performed before and after vascular stenting
      for VBI. The relationship among clinical factors, the incidence and
      characteristics of SAHS were analyzed. The changes of apnea hypopnea index (AHI),
      longest apnea duration (LAD), the total time of apnea and hypopnea (AH%), the
      lowest arterial saturation (LSaO(2)) and oxygen desaturation index (ODI(4))
      before and after vascular stenting were compared. RESULTS: PSG studies were
      performed in 20 cases of VBI. SAHS was confirmed in 17 of the 20 patients,
      including mild (10/20), moderate (3/20) and severe (4/20), all were of
      obstructive. Before stenting therapy, AHI was 11.3/h (6.3 - 23.6)/h, but was
      5.0/h (1.6 - 12.7)/h after therapy. LAD was (31.5 +/- 18.6) s vs (19.5 +/- 12.4)
      s, LSaO2 was (83.6 +/- 7.1)% vs (86.1 +/- 3.3)%, the AH% was [2.3 (0.6% - 9.8)%]
      vs [6.9% (2.6 - 14.3)%], ODI(4) was 10.1/h (5.3 - 29.0)/h vs 5.8/h (2.7 -
      17.0)/h, respectively before and after stenting. AHI, LAD and ODI(4) were
      significantly decreased and LSaO(2) was increased after stenting for VBI.
      CONCLUSION: This series of patients with cerebravascular ischemia caused by
      vertebrobasilar artery stenosis had a high prevalence of obstructive sleep apnea.
      Vertebrobasilar vascular stenting was shown to be a reliable method of decreasing
      the degree of sleep-disordered breathing and hypoxia for SAHS patients with
      vertebrobasilar artery stenosis.

PMID- 18336766
TI  - [Association between plasma interleukin-18 levels and atherosclerosis in patients
      with sleep apnea hypopnea syndrome].
AB  - OBJECTIVE: To investigate the association between plasma interleukin-18 (IL-18)
      levels and atherosclerosis in patients with obstructive obstructive sleep apnea
      hypopnea syndrome (OSAHS). METHODS: Based on apnea hypopnea index (AHI) during
      sleep monitored by polysomnography, 52 male patients with OSAHS were recruited
      and divided into a mild OSAHS group (n = 16), a moderate group (n = 18), and a
      severe group (n = 18). Eighteen healthy subjects were selected as the control
      group. Twenty patients with moderate-to-severe OSAHS underwent continuous
      positive airway pressure (CPAP) treatment. HDL5000 color Doppler ultrasound was
      used to measure intima-media thickness (IMT) of the jugular arteries. Plasma IL
      18 levels were measured by ELISA. Analysis of variance, paired-samples T test and
      Pearson correlation analysis were used for statistics. RESULTS: Compared with the
      plasma IL-18 levels in the control group [(250 +/- 76) ng/L], there was a
      significant increase in the mild OSAHS group [(352 +/- 76) ng/L], moderate group
      [(600 +/- 84) ng/L], and severe OSAHS group [(798 +/- 110) ng/L (all P < 0.01)].
      Moreover, there was a significant difference in plasma IL-18 levels among three
      OSAHS groups (P < 0.01). The jugular arterial IMT was significantly greater in
      severe OSAHS group than that in mild OSAHS group (P < 0.01). The plasma IL-18
      levels were positively correlated with jugular arterial IMT (r = 0.486, P <
      0.001) and with AHI (r = 0.865, P < 0.001) respectively. After CPAP treatment,
      plasma IL-18 levels were significantly decreased but the jugular arterial IMT did
      not change significantly. CONCLUSION: Our study demonstrated that jugular
      arterial IMT and plasma IL-18 levels were significantly increased and closely
      correlated. The elevation of plasma IL-18 levels was correlated with the severity
      (AHI and miniSaO(2)) of OSAHS.

PMID- 18336767
TI  - [The association between polymorphism of the serotonin 2A, 2C receptor genes and
      obstructive sleep apnea-hypopnea syndrome in Han population].
AB  - OBJECTIVE: To investigate the association between polymorphisms of the serotonin
      2A, 2C receptor genes and obstructive sleep apnea-hypopnea syndrome (OSAHS), and
      therefore to explore the genotypes related to OSAHS. METHODS: The T102C and
      A1438G polymorphisms of the serotonin 2A receptor genes and the G796C
      polymorphisms of the serotonin 2C receptor genes were identified by polymerase
      chain reaction-restricted fragment length polymorphism assay in 119 unrelated
      subjects (including 65 OSAHS patients and 54 normal controls) of "Han" population
      of China. The genotype distribution and the allele frequencies of the
      polymorphisms were compared between the OSAHS group and the control group. The
      effects of polymorphisms in the OSAHS group on parameters of polysomnography and
      indexes correlated with obesity were analyzed. RESULTS: There was no significant
      difference in genotype distribution and allele frequencies of the T102C
      polymorphisms of the serotonin 2A receptor genes between the two groups; the
      frequencies of TT/TC/CC genotype and T/C allele were 27.7% (18/65), 46.2%
      (30/65), 26.1% (17/65), 50.8% (66/130) and 49.2% (64/130), respectively in the
      OSAHS group; but were 27.8% (15/54), 51.8% (28/54), 20.4% (11/54), 53.7% (58/108)
      and 46.3% (50/108), respectively in the control group (chi(2) = 0.616 and 0.203,
      respectively, P > 0.05). The G796C polymorphisms of the serotonin 2C receptor
      genes were as follows: the frequencies of male's G/C allele, female's GG/GC
      genotype and G/C allele were 88.9% (48/54), 11.1% (6/54), 63.6% (7/11), 36.4%
      (4/11), 81.8% (18/22) and 18.2% (4/22), respectively in the OSAHS group; but were
      90.5% (38/42), 9.5% (4/42), 66.7% (8/12), 33.3% (4/12), 83.3% (20/24) and 16.7%
      (4/24), respectively in the control group (chi(2) = 0.007, 0.002 and 0.064,
      respectively, P > 0.05). The frequencies of AA genotype and A allele in the
      A1438G polymorphisms of the serotonin 2A receptor genes in the OSAHS group [63.1%
      (41/65) and 74.6% (97/130), respectively] were significantly higher than those of
      the control one [27.8% (15/54) and 40.7% (44/108), respectively; chi(2) = 18.779
      and 28.035, respectively, P < 0.01]. The OSAHS patients with AA genotype had
      higher obstructive apnea-hypopnea index (OAHI) and longest apnea time (LAT) than
      those with AG/GG genotype [OAHI were (40 +/- 9)/h, (25 +/- 9)/h and (20 +/-
      11)/h, respectively, t = 6.674 and 7.753, respectively, P < 0.05; LAT were (94 +/
      10) s, (88 +/- 9) s and (75 +/- 12) s, respectively, t = 3.278 and 5.682,
      respectively, P < 0.05]. The lowest saturation of blood oxygen in patients with
      AA genotype was significantly lower than that in patients with AG/GG genotype
      [(69 +/- 12)%, (78 +/- 10)% and (80 +/- 9)%, respectively, t = 4.025 and 4.153,
      respectively, P < 0.05]. There was no significant difference in body mass index
      [(26.9 +/- 2.8) kg/m(2), (25.2 +/- 2.7) kg/m(2) and (26.0 +/- 3.7) kg/m(2),
      respectively], neck circumference [(43.3 +/- 2.7) cm, (42.6 +/- 1.8) cm and (42.8
      +/- 2.1) cm, respectively] and waist/hip rate (0.89 +/- 0.12), (0.92 +/- 0.11)
      and (0.90 +/- 0.09), respectively, F = 0.859, 1.296 and 1.078, respectively, P >
      0.05). CONCLUSION: The T102C polymorphisms of the serotonin 2A receptor gene and
      the G796C polymorphisms of the serotonin 2C receptor gene may be not associated
      with OSAHS in subjects of "Han" population of China. The 1438 AA genotype of the
      serotonin 2A receptor gene may be involved in OSAHS, and the A allele may be an
      important candidate gene for OSAHS.

PMID- 18336768
TI  - [The clinical significance of serum tuberculosis specific antigen antibody in the
      diagnosis of tuberculosis].
AB  - OBJECTIVE: To evaluate the significance of serum tuberculosis specific antigen
      (TB-SA) antibody detection in the diagnosis of tuberculosis. METHODS: TB-SA
      antibody in the serum samples from 829 cases of tuberculosis, 278 patients with
      non-tuberculosis lung diseases and 125 healthy volunteers were detected using
      enzyme-linked immunosorbent assay (ELISA). Tuberculosis was confirmed by
      clinical, bacteriology, X-ray examination and pathology studies. RESULTS: The
      sensitivity of TB-SA antibody in diagnosis of bacteriologically positive and
      negative pulmonary tuberculosis and extrapulmonary tuberculosis was 75.1%
      (272/362), 68.9% (226/328) and 71.2% (99/139), respectively; the combined
      sensitivity was 72.0% (597/829), and the specificity 82.1% (331/403). The
      relationship between the OD(405) of TB-SA antibody and PPD positivity showed no
      linear relationship, suggesting that BCG vaccination did not affect the value of
      serum TB-SA antibody. CONCLUSION: The results suggest that measurement of serum
      TB-SA is a relatively sensitive and specific method for the diagnosis and
      differential diagnosis of tuberculosis.

PMID- 18336769
TI  - [Role of connective tissue growth factor on pulmonary artery remodeling in rats
      exposed to smoke].
AB  - OBJECTIVE: To explore the role of connective tissue growth factor (CTGF) on
      pulmonary artery remodeling induced by smoke exposure in rats. METHODS: Thirty
      five male Wistar rats were randomly assigned into a control group (A group), a
      smoke exposure one month group (B group), a smoke exposure and high dose CTGF
      antisense oligonucleotide (ASON) one month group (C group), a smoke exposure and
      low dose CTGF ASON one month group (D group), a smoke exposure two month group (E
      group), a smoke exposure and high dose CTGF ASON two month group (F group), and a
      smoke exposure and low dose CTGF ASON two month group (G group). Pulmonary artery
      remodeling was observed by hematoxylin-eosin staining, and the CTGF mRNA
      expressions of pulmonary arteries were evaluated by RT-PCR. Immunohistochemistry
      methods were performed to determine CTGF protein expression in pulmonary artery
      smooth muscle. The difference between the groups was analyzed. RESULTS: (1) The
      pulmonary artery WA% of the seven groups were respectively (28.6 +/- 1.2)%, (42.5
      +/- 2.3)%, (33.7 +/- 1.8)%, (42.1 +/- 2.4)%, (49.6 +/- 2.1)%, (34.3 +/- 1.9)% and
      (38.4 +/- 2.0)%. There was significant difference between B group and C group (q
      = 5.09, P < 0.01). Compared to E group, there were significant decreases in F
      group and G group (q = 8.15, 3.75, all P < 0.05). (2) The CTGF protein
      expressions (A value) of pulmonary artery smooth muscle were respectively 0.098
      +/- 0.015, 0.159 +/- 0.023, 0.118 +/- 0.017, 0.153 +/- 0.022, 0.406 +/- 0.036,
      0.109 +/- 0.012 and 0.146 +/- 0.024. There was significant difference between B
      group and C group (q = 3.26, P < 0.05). Compared to E group, there were
      significant decreases in F group and G group (q = 67.08, 18.09, all P < 0.01).
      (3) The CTGF mRNA expressions (A(CTGF)/A(beta-actin)) of pulmonary artery were
      respectively 0.051 +/- 0.010, 0.823 +/- 0.096, 0.216 +/- 0.056, 0.810 +/- 0.085,
      2.452 +/- 0.267, 0.207 +/- 0.062 and 0.509 +/- 0.067. There was significant
      difference between B group and C group (q = 53.50, P < 0.01). Compared to E
      group, there were significant decreases in F group and G group (q = 132.22,
      93.70, all P < 0.01). CONCLUSION: Administration of CTGF ASON in vivo could
      significantly reduce pulmonary artery remodeling induced by smoke exposure in
      rats, indicating that CTGF may play an important role in pulmonary hypertension.

PMID- 18336770
TI  - [The protective effect of angiopoietin-1 on early acute lung injury induced by
      oleic acid in mice].
AB  - OBJECTIVE: To observe the protective effects of angiopoietin-1 on acute lung
      injury (ALI) induced by oleic acid at early stage in mice and to investigate the
      expression changes of vascular endothelial growth factor (VEGF). METHODS: Ninety
      six female BALB/c mice were randomly divided into 4 groups (n = 24). The control
      group was given normal saline (0.9 ml/kg) intravenously. The ALI group was
      treated with oleic acid (0.9 ml/kg) intravenously to induce ALI. In the control +
      angiopoietin-1 group, the mice were injected intraperitoneally with angiopoietin
      1 (312.5 microg/kg) 4 h after normal saline administration. In the ALI +
      angiopoietin-1 group, the mice were injected intraperitoneally with angiopoietin
      1 (312.5 microg/kg) 4 h after oleic acid treatment. Then 8 h later 12 mice were
      randomly taken from each group for bronchoalveolar lavage fluid (BALF) analysis
      including the protein level, cell count and differentials, and the level of IL-6
      and VEGF. The wet/dry weight (W/D) of the right lung, the level of IL-6 and VEGF
      in serum, pathological changes of the left lung and VEGF expressions in lung
      tissues were examined for the rest of mice in each group. The level of IL-6 and
      VEGF in both serum and BALF were measured by enzyme-linked-immunosorbent assay
      (ELISA). Pathological changes of the lung tissue were examined and scored with
      light microscrope. The expression of VEGF was immunohistochemically detected in
      lung tissues as integrated optic density (A) measured with Image Pro Plus 5.1
      software. RESULTS: The W/D, the protein level, the tota1 cel1 number and
      differential of polymorphonuclear leukocytes in BALF, the IL-6 level in both
      serum and BALF, the VEGF level in serum were significantly decreased in the ALI +
      angiopoietin-1 group [4.09 +/- 0.14, (176 +/- 13) microg/ml, (34.4 +/- 4.1) x
      10(4)/L, (19.85 +/- 3.93) x 10(3)/L, (1318 +/- 62) pg/ml, (652 +/- 17) pg/ml, (48
      +/- 5) pg/ml] as compared to the ALI group [5.32 +/- 0.51, (227 +/- 12)
      microg/ml, (42.2 +/- 5.2) x 10(4)/L, (26.22 +/- 2.22) x 10(3)/L, (1510 +/- 117)
      pg/ml, (744 +/- 13) pg/ml, (74 +/- 5) pg/ml, t = 8.16, 9.92, 4.02, 4.88, 5.03,
      19.18, 14.81 respectively, all P < 0.01]. Pathological scores in the ALI +
      angiopoietin-1 group (1.84 +/- 0.12) improved as compared to those in the ALI
      group (3.44 +/- 0.21, t = 24.16, P < 0.01), and the VEGF level in BALF of the ALI
      + angiopoietin-1 group (179 +/- 15) pg/ml was higher than that of the ALI group
      (140 +/- 20) pg/ml (t = 5.31, P < 0.01). The expressions of VEGF in the lung
      tissues indicated by A (549 +/- 72) in the ALI + angiopoietin-1 group were higher
      than those in the ALI group (342 +/- 85, t = 5.22, P < 0.01), but lower than
      those in the control group (768 +/- 111) (t = 5.35, P < 0.01). The above
      measurements of the control + angiopoietin-1 group showed no difference compared
      to the control group (t = 0.12, 0.53, 1.27, 2.28, 1.18, 0.34, 0.13, 0.25, 0.58,
      0.69 respectively, all P > 0.05). Statistical analysis was done using SPSS 10.0
      software. Data are expressed as mean +/- s, with statistical significance
      declaved for probility valaes < 0.05. LSD-t test was used for group comparison.
      One-factor ANOVA was used for mdlti-group comparison. CONCLUSIONS: Angiopoietin-1
      is effective in relieving the severity of acute lung injury induced by oleic acid
      in mice at early stage and up-regulating VEGF expression in BALF and lung tissues
      but down-regulating VEGF expression in serum. The results suggest that
      angiopoietin-1 may exert beneficial effects on ALI.

PMID- 18336772
TI  - [Activation related genes of memory CD(4)(+) T cells in asthma patients].
AB  - OBJECTIVE: To screen and identify the genes of activated memory CD(4)(+) T cells
      in asthma. METHODS: Differential display polymerase chain reaction (DDPCR) was
      utilized to identify genes of memory CD(4)(+) T cells after activation from
      asthmatic patients and normal individuals, and the mRNA levels of the
      differentially expressed genes were analyzed by reverse transcription-polymerase
      chain reaction (RT-PCR). RESULTS: Nineteen differentially expressed cDNA
      fragments were isolated. The homology analysis indicated that two fragments
      possessed a high degree of homology with interleukin-7 (IL-7) mRNA and MM-1 mRNA.
      RT-PCR confirmed that IL-7 mRNA and MM-1 mRNA levels were increased in memory
      CD(4)(+) T cells after activation in asthmatic patients (0.390 +/- 0.029, 0.629
      +/- 0.047, F = 983, 1264 respectively, all P < 0.05). CONCLUSION: The up
      regulated expression of IL-7 and MM-1 genes in memory CD(4)(+) T cells after
      activation may be a molecular mechanism that differentiates the response to
      allergens of asthma patients from normal individuals.

PMID- 18336773
TI  - [Relationship between polymorphisms of DNA repair gene XRCC3 and susceptibility
      to lung cancer].
AB  - OBJECTIVE: To study the polymorphisms of DNA repair gene XRCC3 and the
      relationship between genetic variations and susceptibility to lung cancer.
      METHODS: A case-control study of 291 patients with lung cancer and 273 cancer
      free subjects as a control group was conducted from September 2006 to January
      2007 to detect XRCC3 polymorphisms at loci. Genotypes of XRCC3 were analyzed by
      real time PCR using Taqman probes. RESULTS: Compared with never smoking subjects
      with wild homozygous genotype (Thr/Thr), smokers with the same genotytpe
      (Thr/Thr) had increased risk of lung cancer, adjusted odds ratio (OR) was 2.467
      (95% CI: 1.49 - 4.08, P < 0.001). Smokers with the heterozygous genotype
      (Thr/Met) also had increased risk of lung cancer, adjusted OR was 2.283 (95% CI:
      1.21 - 6.60, P < 0.05). XRCC3 codon 241 homozygous genotype (Thr/Thr) and pack
      years of smoking less than 30 had a weak protective effect on adenocarcinoma (OR
      = 0.49, 95% CI: 0.26 - 0.93, P < 0.05). Allel Met of XRCC3 codon 241 and smoking
      conferred an increased risk of squamous cell carcinoma (OR = 9.69, 95% CI: 3.27 -
      28.72, P < 0.01). Those with allel Met of XRCC3 codon 241 and pack-years of
      smoking less than 30 or more than 30 had different risk of squamous cell
      carcinoma, the OR was 8.00 (95% CI: 1.97 - 32.52, P < 0.01), and 11.67 (95% CI:
      2.98 - 45.73, P < 0.01) respectively. CONCLUSION: The results demonstrated that
      genetic polymorphism of XRCC3 DNA repair gene may contribute to the
      susceptibility to lung cancer and have synergistic effect with smoking.

PMID- 18336784
TI  - Toward Systeme International d'Unite-traceable protein quantification: from amino
      acids to proteins.
AB  - Here we present a demonstration of the proof of principle that absolute
      concentration of a protein within a mixture of other proteins can be measured
      with SI traceability. The method used was based on tryptic digestion of a protein
      followed by quantification using double exact matching isotope dilution mass
      spectrometry (IDMS) of the peptides released. To provide full SI traceability to
      measurements of protein concentration we demonstrated a method of SI traceable
      peptide quantification in which the peptide standards used were quantified by an
      amino acid analysis method that incorporated double exact matching IDMS and amino
      acid standards of known purity. The concentration of the protein was therefore
      determined based upon the concentration of tryptic peptides, which in turn had
      been quantified based upon amino acid standards. This allowed fully SI-traceable
      measurements of protein concentration to be made. Important caveats in the
      implementation of this approach are also discussed and examples of how these can
      have detrimental effects on the measurements are shown.

PMID- 18336785
TI  - Effects of iron oxide incorporation for long term cell tracking on MSC
      differentiation in vitro and in vivo.
AB  - Successful cell therapy will depend on the ability to monitor transplanted cells.
      With cell labeling, it is important to demonstrate efficient long term labeling
      without deleterious effects on cell phenotype and differentiation capacity. We
      demonstrate long term (7 weeks) retention of superparamagnetic iron oxide
      particles (SPIO) by mesenchymal stem cells (MSCs) in vivo, detectable by MRI. In
      vitro, multilineage differentiation (osteogenic, chondrogenic and adipogenic) was
      demonstrated by histological evaluation and molecular analysis in SPIO labeled
      and unlabeled cells. Gene expression levels were comaparable to unlabeled
      controls in adipogenic and chondrogenic conditions however not in the osteogenic
      condition. MSCs seeded into a scaffold for 21 days and implanted subcutaneously
      into nude mice for 4 weeks, showed profoundly altered phenotypes in SPIO labeled
      samples compared to implanted unlabeled control scaffolds, indicating
      chondrogenic differentiation. This study demonstrates long term MSC traceability
      using SPIO and MRI, uninhibited multilineage MSC differentiation following SPIO
      labeling, though with subtle but significant phenotypical alterations.

PMID- 18336786
TI  - Forkhead box transcription factors Foxa1 and Foxa2 are important regulators of
      Muc2 mucin expression in intestinal epithelial cells.
AB  - The mucin Muc2 is the main component of the intestinal mucus layer and thus plays
      important roles in intestinal protection. Therefore, it is important to
      understand its regulation during goblet cell differentiation. Foxa1 and Foxa2
      forkhead box transcription factors (TFs) participate in transcriptional programs
      governing intestinal cell differentiation. Using immunohistochemistry, we showed
      a spatio-temporal pattern of expression of both TFs in developing and adult mouse
      intestine and their expression in Muc2-expressing intestinal cells. Down
      regulation of Foxa1 and Foxa2 by RNA interference in cultured intestinal cells
      decreased Muc2 mRNA level by half, and abolished Muc2 protein expression.
      Chromatin immunoprecipitation and gel shift assays showed that these two TFs
      directly bind to the Muc2 promoter. Co-transfection experiments indicated that
      both TFs activate the Muc2 promoter and that mutations of three Foxa cis-elements
      inhibit Muc2 transactivation. In conclusion, this work identifies Foxa1 and Foxa2
      as important regulators of Muc2 expression in the intestine.

PMID- 18336787
TI  - Peroxynitrite inactivates human-tissue inhibitor of metalloproteinase-4.
AB  - Peroxynitrite, via post-translational modifications to target proteins,
      contributes to cardiovascular injury and cancer. Since tissue inhibitor of
      metalloproteinase-4 (TIMP-4), the activity of which is impaired in both
      pathological conditions, has several amino acid residues susceptible to
      peroxynitrite, we investigated its role as a potential target of peroxynitrite.
      Peroxynitrite-induced nitration and oligomerization of TIMP-4 attenuated its
      inhibitory activity against MMP-2 activity and endothelial or tumor cell
      invasiveness. Moreover, cell treatment with peroxynitrite promoted the nitration
      of endogenous TIMP-4. HPLC/ESI-MS/MS analysis of peroxynitrite-treated TIMP-4
      showed modifications at Y114, Y195, Y188 and Y190. In conclusion, TIMP-4
      nitration might be a potential mechanism contributing to cardiovascular disease
      and cancer.

PMID- 18336788
TI  - Ocular adnexal mucosa-associated lymphoid tissue lymphoma with polyclonal
      hypergammaglobulinemia.
AB  - PURPOSE: To determine the characteristics of patients with primary ocular adnexal
      mucosa-associated lymphoid tissue (MALT) lymphoma associated with polyclonal
      hypergammaglobulinemia. DESIGN: Case series study. METHODS: Among 81 Japanese
      patients with primary ocular adnexal MALT lymphoma, seven patients (9%) were
      diagnosed with polyclonal hypergammaglobulinemia. Patient clinical data included
      a history of autoimmune disease and dissemination. Peripheral blood collected
      from all patients was analyzed for serum levels of rheumatoid factor, soluble
      interleukin-2 receptor (sIL-2R), and immunoglobulins at the time of diagnosis and
      after each treatment. RESULTS: Seven patients with polyclonal
      hypergammaglobulinemia had elevated serum levels of rheumatoid factor, sIL-2R,
      immunoglobulin G (IgG), and immunoglobulin E (IgE) at the time of diagnosis. One
      patient had Sjogren syndrome. Six patients (86%) had a dissemination of the MALT
      lymphoma or lymphadenopathy at the time of diagnosis. Histopathologic examination
      of the patients with lymphadenopathy revealed not only MALT lymphoma but also
      secondary follicles. None of the seven patients showed improvement in serum
      levels of IgG, rheumatoid factor, or sIL-2R in spite of complete regression of
      the ocular lesions after radiotherapy. After administration of
      cyclophosphamide/doxorubicin/vincristine/prednisone and/or rituximab to three
      patients, all three showed improved serum levels of IgG, rheumatoid factor, and
      sIL-2R. CONCLUSIONS: Patients with ocular adnexal MALT lymphoma and polyclonal
      hypergammaglobulinemia have elevated serum levels of rheumatoid factor, sIL-2R,
      and IgE, and high dissemination or lymphadenopathy. These unique characteristics
      may correlate with the systemic immunologic imbalances.

PMID- 18336789
TI  - Anterior chamber depth and chamber angle and their associations with ocular and
      general parameters: the Beijing Eye Study.
AB  - PURPOSE: To investigate the normative data of anterior chamber depth (ACD) and
      angle width and their associations in Chinese adults. DESIGN: Population-based
      study. METHODS: The Beijing Eye Study 2006 included 3,251 subjects (73.3%) (aged
      45+ years) out of 4,439 subjects who participated in the 2001 survey and who
      returned for reexamination. The subjects underwent an ophthalmologic examination
      including measurement of the anterior chamber dimensions by slit-lamp-based
      optical coherence tomography (OCT). RESULTS: Out of the 3,251 subjects, OCT
      measurements were available for 2,985 subjects (91.8%). Mean ACD measured 2.42 +/
      0.34 mm and the mean anterior chamber angle (ACA) was 38.3 +/- 16.3 degrees. In
      multivariate analysis, a shallow chamber depth was significantly associated with
      age (P < .001), hyperopic refractive error (P < .001), female gender (P < .001),
      short body stature (P = .003), nuclear cataract (P = .03), central corneal
      thickness [CCT] (P < .001), large optic disk (P < .001), and presence of chronic
      angle-closure glaucoma (P < .001). Correspondingly, a narrow ACA was associated
      with age (P < .001), female gender (P < .001), hyperopia (P < .001), nuclear
      cataract (P < .001), short body stature (P = .001), large optic disk (P < .001),
      and angle-closure glaucoma (P < .001). Chamber depth and angle width were not
      associated with presence of age-related maculopathy and diabetic retinopathy.
      CONCLUSIONS: A shallow anterior chamber and a narrow chamber angle in Chinese
      adults are associated with age, female gender, hyperopia, nuclear cataract, small
      optic disk, short body stature, CCT, and chronic angle-closure glaucoma. These
      data may be helpful to explain anatomic relationships of the anterior segment of
      the eye, and to elucidate risk factors of angle-closure glaucoma.

PMID- 18336790
TI  - Application of the Strain Index in multiple task jobs.
AB  - Six different methods to calculate the Strain Index (SI) scores for jobs with
      multiple forces/tasks were developed. Exposure data of 733 subjects from 12
      different worksites were used to calculate these SI scores. Results show that
      using different SI computation methods could result in different SI scores, hence
      different risk level classifications. However, some simpler methods generated SI
      scores were comparable to the more complicated composite SI method. Despite
      differences in the scores between the six different SI computation methods,
      Spearman rank-order correlation coefficients of 0.61-0.97 were found between the
      methods. With some confidence, ergonomic practitioners may use simpler methods,
      depending on their specificity requirement in job evaluations and available
      resources. Some SI computation methods may tend to over-estimate job risk levels,
      while others may tend to under-estimate job risk levels, due to different ways
      used in obtaining the various SI parameters and computations.

PMID- 18336791
TI  - The effects of an office ergonomics training and chair intervention on worker
      knowledge, behavior and musculoskeletal risk.
AB  - A large-scale field intervention study was undertaken to examine the effects of
      office ergonomics training coupled with a highly adjustable chair on office
      workers' knowledge and musculoskeletal risks. Office workers were assigned to one
      of three study groups: a group receiving the training and adjustable chair
      (n=96), a training-only group (n=63), and a control group (n=57). The office
      ergonomics training program was created using an instructional systems design
      model. A pre/post-training knowledge test was administered to all those who
      attended the training. Body postures and workstation set-ups were observed before
      and after the intervention. Perceived control over the physical work environment
      was higher for both intervention groups as compared to workers in the control
      group. A significant increase in overall ergonomic knowledge was observed for the
      intervention groups. Both intervention groups exhibited higher level behavioral
      translation and had lower musculoskeletal risk than the control group.

PMID- 18336792
TI  - Ergonomics and obesity.

PMID- 18336793
TI  - Comparative properties of recombinant human and bovine matrix metalloproteinase
      20.
AB  - INTRODUCTION: Matrix metalloproteinase-20 (MMP-20) is a predominant enzyme for
      the progressive processing of enamel extracellular matrix protein components
      (primarily amelogenin) during the early stages of enamel formation. So far, the
      recombinant porcine, mouse and bovine MMP-20 have been cloned and used
      extensively in the researches of tooth enamel development. The homology of these
      MMP-20s to human MMP-20 is approximately 80%. The effect of sequence differences
      on the properties of these enzymes is poorly understood even though they have
      been used to hydrolyse amelogenins from different species. OBJECTIVE: Our goal is
      to compare the characteristics between recombinant human MMP-20 (rhMMP-20) and
      bovine MMP-20 (rbMMP-20). DESIGN: rhMMP-20 and rbMMP-20 were parallelly
      expressed, purified and activated. The SDS-PAGE, zymography and quenched peptide
      assay were used for characterization and comparisons. RESULTS: Both proteases
      were activated by autocatalysis in a similar pattern of fragmentation.
      Dynamically, rbMMP-20 autoactivated faster and digested a fluorescence-quenched
      peptide Mca-PLGL-Dpa-AR, a non-amelogenin substrate, more efficiently than rhMMP
      20. However, rhMMP-20 showed higher enzymatic activity for a human amelogenin
      substrate and in addition, it created an extra cleavage site at its C-terminus.
      CONCLUSIONS: The differences in their catalytic properties and substrate
      specificities may be attributed to the sequence divergence of MMP-20 between
      species, especially in the hinge region.

PMID- 18336794
TI  - The use of safety behaviours to manage intrusive memories in depression.
AB  - Cognitive models of clinical disorders conceptualise cognitive and behavioural
      safety-seeking behaviours as central to symptom persistence because they prevent
      disconfirmation of key maintaining beliefs. Despite growing evidence of the role
      of negative beliefs about intrusive memories in depression, it remains unclear
      why such beliefs persist. Accordingly, we examined whether safety behaviours in
      response to unhelpful beliefs about intrusive memories might play a role in their
      maintenance. Eighteen high dysphoric (i.e., BDI-II>or=12) individuals who
      reported an intrusive negative autobiographical memory in the past week completed
      a battery of measures about their memory, associated negative beliefs and safety
      behaviours adopted in response to their beliefs. The most commonly endorsed
      beliefs reflected themes of wanting to control memories (e.g., 'I should be able
      to rid my mind of this memory') and self-deprecation about experiencing them
      (e.g., 'Because I can't control this memory, I am a weak person'). The beliefs
      prompted a range of safety behaviours, with cognitive distraction being the most
      common. The findings demonstrate that safety behaviours are common in response to
      maladaptive beliefs about intrusive memories. Treatment developments in this area
      are needed, and should incorporate strategies to challenge beliefs about
      memories, reduce the use of safety behaviours, and promote processing of
      intrusive memories.

PMID- 18336795
TI  - Role of proline 1150 in functional interactions between the membrane spanning
      domains and nucleotide binding domains of the MRP1 (ABCC1) transporter.
AB  - The ATP-binding cassette multidrug resistance protein 1 (MRP1) mediates ATP
      dependent cellular efflux of drugs and organic anions. We previously described a
      mutant, MRP1-Pro1150Ala, which exhibits selectively increased estradiol
      glucuronide (E217betaG) and methotrexate transport as well as altered
      interactions with ATP. We have now further explored the functional importance of
      MRP1-Pro1150 at the interface of transmembrane helix 15 and cytoplasmic loop 7
      (CL7) by replacing it with Gly, Ile, Leu and Val. All four mutants exhibited a
      phenotype similar to MRP1-Pro1150Ala with respect to organic anion transport and
      [gamma32P]8N3ATP photolabeling. They also displayed very low levels of substrate
      independent vanadate-induced trapping of [alpha32P]8N3ADP. To better understand
      the relationship between the altered nucleotide interactions and transport
      activity of these mutants, [alpha32P]8N3ADP trapping experiments were performed
      under different conditions. Unlike leukotriene C4, E217betaG decreased
      [alpha32P]8N3ADP trapping by both wild-type and mutant MRP1. [alpha32P]8N3ADP
      trapping by MRP1-Pro1150Ala could be increased by using Ni2+ instead of Mg2+, and
      by decreasing temperature; however, the transport properties of the mutant
      remained unchanged. We conclude that the reduced [alpha32P]8N3ADP trapping
      associated with loss of Pro1150, or the presence of E217betaG, is due to enhanced
      ADP release following ATP hydrolysis rather than a reduction in ATP hydrolysis
      itself. We hypothesize that loss of Pro1150 alters the role of CL7 as a coupling
      helix that mediates signaling between the nucleotide binding domains and some
      substrate binding sites in the membrane spanning domains of MRP1.

PMID- 18336796
TI  - Regarding "Systematic review: pharmacological and behavioral treatment for
      trichotillomania".

PMID- 18336798
TI  - Brain activity during interval timing depends on sensory structure.
AB  - Precise timing is crucial for accurate perception and action in the range of
      hundreds of milliseconds. One still unresolved question concerns the influence of
      sensory information content on timing mechanisms. Numerous studies have converged
      to suggest that the CNV (Contingent Negative Variation), a slow negative wave
      that develops between two events, notably reflects temporal processing of the
      interval between these two events. The present study aimed at investigating CNV
      activity in duration discrimination tasks using either filled (continuous tones)
      or empty intervals (silent periods bounded by two brief tones). Participants had
      to compare a test duration with a 600-ms standard. Time perception was markedly
      better in the 'empty' than in the 'filled' condition. Electrophysiological
      analyses performed on the longest test duration (794 ms) of the comparison phase
      revealed an effect of the sensory structure on both the CNV amplitude and CNV
      time-course. The CNV amplitude was larger for filled than for empty intervals,
      suggesting a superimposition of timing-dependent activity and sensory sustained
      activity. Furthermore, the CNV time-course paralleled the temporal structure of
      the memorized sensory event: for filled intervals, the CNV amplitude stopped
      increasing at 600 ms, i.e. the expected end of the continuous tone; for empty
      intervals, in contrast, the CNV amplitude precisely increased at 600 ms, i.e. the
      expected onset of the second brief tone. These results suggest that the CNV
      reflects the mental rehearsal of the memorized sensory event, in line with the
      idea that temporal processing in the sub-second range is based on sensory
      information.

PMID- 18336799
TI  - Molecular cloning and expression analysis of three cadherin-8 isoforms in the
      embryonic chicken brain.
AB  - Three types of full-length cDNAs encoding chicken cadherin-8 (Cdh8) were
      identified and their expression in the embryonic chicken brain was investigated.
      The longest type of cDNA is closely similar to that of other classic cadherins,
      and the predicted protein shows a high similarity to rat and human Cdh8. The
      second type of cDNA is considerably shorter. The deduced protein lacks the
      cytoplasmic tail and the transmembrane domain, and contains a truncated fifth
      cadherin repeat in the extracellular domain (EC5; 68 amino acids), suggesting
      that it is a soluble isoform. The third type resembles the second one but is even
      shorter (only 30 amino acids in EC5). All types contain unique short sequences at
      their C terminus. Genomic analysis demonstrated that all of the three Cdh8
      isoforms are located on chromosome 11, and consist of 12, 10, and 9 exons,
      respectively. Semi-quantitative RT-PCR with type-specific primers showed that the
      transcription of the three Cdh8 isoforms was temporally and spatially regulated
      in different parts of the embryonic chicken brain. The distinct regulation of
      gene expression suggested that the three isoforms likely play different roles
      during brain development. Northern blot analysis revealed that the transcription
      of the long isoform was much stronger than that of the two shorter ones. In situ
      hybridization showed that the long isoform of Cdh8 is expressed by a specific
      subset of brain nuclei, regions and layers in all major parts of the brain.

PMID- 18336800
TI  - A polysaccharide of Alloiococcus otitidis, a new pathogen of otitis media:
      chemical structure and synthesis of a neoglycoconjugate thereof.
AB  - Alloiococcus otitidis is a recently discovered Gram-positive bacterium that has
      been linked with otitis media (middle ear infections). In this study, we describe
      the structure of a novel capsular polysaccharide (PS) expressed by the type
      strain of A. otitidis, ATCC 51267, and the synthesis of a glycoconjugate composed
      of the capsule PS and bovine serum albumin (BSA). The capsule PS of A. otitidis
      type-strain was determined to be a repeating trisaccharide composed of 3
      substituted N-acetyl-D-glucosamine (GlcpNAc), 6-substituted N-acetyl-D
      galactosamine (GalpNAc), and 4-substituted D-glucuronic acid (GlcpA), of which
      the majority was amidically decorated with L-glutamic acid (Glu): {-->6)-beta
      GalpNAc-(1-->4)-[Glup-->6]-beta-GlcpA-(1-->3)-beta-GlcpNAc-(1}n. Monomeric
      analysis performed on other A. otitidis strains revealed that similar components
      were variably expressed, but Glu appeared to be a regular constituent in all the
      strains examined. Due to the suitable presence of GlcpA and Glu, our approach for
      glycoconjugate synthesis employed a carbodiimide-based strategy with activation
      of available carboxyl groups by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
      hydrochloride (EDC), which afforded direct coupling between the capsule PS and
      BSA. Analysis by mass spectrometry indicated that this A. otitidis capsule PS-BSA
      conjugate was composed of BSA units that carried up to seven capsule PSs. This
      work represents the first report in the literature describing an A. otitidis cell
      surface carbohydrate and the synthesis of a glycoconjugate preparation thereof.
      Presently, we are formulating plans to immunologically evaluate this A. otitidis
      glycoconjugate vaccine in animals.

PMID- 18336802
TI  - Synthesis of UDP-glucose derivatives modified at the 3-OH as potential chain
      terminators of beta-glucan biosynthesis.
AB  - A series of UDP-D-glucose derivatives and precursors that have been modified at C
      3 were synthesised from D-glucose as potential chain terminators of beta-glucan
      biosynthesis. None of the UDP-derivatives or the precursors tested displayed
      significant anti-fungal activity in a series of germination assays on the
      dermatophyte Trichophyton rubrum.

PMID- 18336801
TI  - S-layer nanoglycobiology of bacteria.
AB  - Cell surface layers (S-layers) are common structures of the bacterial cell
      envelope with a lattice-like appearance that are formed by a self-assembly
      process. Frequently, the constituting S-layer proteins are modified with
      covalently linked glycan chains facing the extracellular environment. S-layer
      glycoproteins from organisms of the Bacillaceae family possess long, O
      glycosidically linked glycans that are composed of a great variety of sugar
      constituents. The observed variations already exceed the display found in
      eukaryotic glycoproteins. Recent investigations of the S-layer protein
      glycosylation process at the molecular level, which has lagged behind the
      structural studies due to the lack of suitable molecular tools, indicated that
      the S-layer glycoprotein glycan biosynthesis pathway utilizes different modules
      of the well-known biosynthesis routes of lipopolysaccharide O-antigens. The
      genetic information for S-layer glycan biosynthesis is usually present in S-layer
      glycosylation (slg) gene clusters acting in concert with housekeeping genes. To
      account for the nanometer-scale cell surface display feature of bacterial S-layer
      glycosylation, we have coined the neologism 'nanoglycobiology'. It includes
      structural and biochemical aspects of S-layer glycans as well as molecular data
      on the machinery underlying the glycosylation event. A key aspect for the full
      potency of S-layer nanoglycobiology is the unique self-assembly feature of the S
      layer protein matrix. Being aware that in many cases the glycan structures
      associated with a protein are the key to protein function, S-layer protein
      glycosylation will add a new and valuable component to an 'S-layer based
      molecular construction kit'. In our long-term research strategy, S-layer
      nanoglycobiology shall converge with other functional glycosylation systems to
      produce 'functional' S-layer neoglycoproteins for diverse applications in the
      fields of nanobiotechnology and vaccine technology. Recent advances in the field
      of S-layer nanoglycobiology have made our overall strategy a tangible aim of the
      near future.

PMID- 18336803
TI  - Structural analysis of a polysaccharide isolated from the aqueous extract of an
      edible mushroom, Pleurotus sajor-caju, cultivar Black Japan.
AB  - A water-soluble polysaccharide, isolated from the aqueous extract of an edible
      mushroom Pleurotus sajor-caju, cultivar Black Japan was found to consist of D
      glucose and D-galactose in a molar ratio of 3:1. On the basis of total acid
      hydrolysis, methylation analysis, and NMR experiments (1H, 13C, DQF-COSY, TOCSY,
      NOESY, ROESY, HMQC, and HMBC) the structure of the polysaccharide was established
      as [Formula: see text].

PMID- 18336804
TI  - Facile synthesis of methyl alpha- and beta-D-[6-(3)H]galactofuranosides from D
      galacturonic acid. Substrates for the detection of galactofuranosidases.
AB  - Galactofuranose metabolism is a good target for the development of novel
      chemotherapeutic agents for the treatment of some microbial infections. A simple
      procedure for the synthesis of methyl (methyl alpha,beta-D
      galactopyranosid)uronate followed by NaB(3)H(4) reduction gave a straightforward
      access to radiolabeled substrates for galactofuranosidases.

PMID- 18336805
TI  - Smith degradation of the O-antigenic polysaccharide of Salmonella Dakar:
      structural studies of the products.
AB  - Two different oligosaccharides were obtained from the Smith degradation of the O
      polysaccharide isolated from the lipopolysaccharide of Salmonella Dakar. The
      structures of these oligosaccharides were investigated by chemical analysis, NMR
      spectroscopy and MALDI-TOF mass spectrometry. The following structures of these
      products were determined: alpha-D-GalpNAc-(1-->4)-alpha-D-Quip3NAc-(1-->3)-alpha
      L-Rhap-(1-->2)-threitol and [Formula: see text] where Quip3NAc is 3-acetamido-3,6
      dideoxyglucose. The reaction products confirmed the structure of the repeating
      unit of the Salmonella Dakar O-polysaccharide reported previously [Kumirska, J.;
      Szafranek, J.; Czerwicka, M.; Paszkiewicz, M.; Dziadziuszko, H.; Kunikowska, D.;
      Stepnowski, P. Carbohydr. Res. 2007,342, 2138-2143].

PMID- 18336806
TI  - 'Naturalization' of textile disperse dyes through glycoconjugation: the case of a
      bis(2-hydroxyethyl) group containing azo dye.
AB  - A family of five strictly related glycoconjugated azo dyes (GADs), characterized
      by the presence of the same chromophore and a variable number (1-4) of
      deprotected hexose units, has been prepared by employing succinate bridges for
      connecting the azo dye and the sugar portions. The modulation of the hydrophilic
      portion determines the appreciable changes in the water solubility of GADs. In
      all the cases, however, hydrophobic fibres (polyester) were homogeneously dyed
      with GADs at temperatures lower than that used for original azo dyes, at
      atmospheric pressure, and avoiding the use of surfactants. Furthermore, GADs show
      an interesting multipurpose character leading to dyeing well also the natural
      fibres as, for instance, wool. The presence of a variable number of hexose units
      in the different GADs determines some changes in the colour intensity of dyed
      fabrics, but in all the cases an appreciable rubbing and water fastness were
      maintained.

PMID- 18336807
TI  - Chemopreventive and therapeutic modulation of green tea polyphenols on drug
      metabolizing enzymes in 4-Nitroquinoline 1-oxide induced oral cancer.
AB  - Oral cancer is one of the most common cancers in the world. Drugs can modulate
      the expression of drug metabolizing enzymes and are useful in chemoprevention as
      well as therapy in cancer. 4-Nitroquinoline 1-oxide (4-NQO) is used to induce
      oral cancer in the present study. In the present investigation, the effect of
      green tea polyphenols (GTP) on the activities of cytochrome b5, cytochrome P450,
      cytochrome b5 reductase (cyt b5 R), cytochrome P450 reductase (cyt P450 R), arryl
      hydrocarbon hydroxylase (AHH), DT-diaphorase (DTD)(Phase I enzymes) and
      glutathione-S-transferase (GST) and UDP-glucuronyl transferase (UDP-GT) (Phase II
      enzymes) were assessed in tongue and oral cavity. In induced rats, there was a
      decrease in the activity of Phase II enzymes and an increase in the activity of
      Phase I enzymes. On supplementation of GTP by both simultaneous and post
      treatment mode (200mg/kg) there was a significant increase in the activity of GST
      and UDP-GT and a significant decrease in the activity of Phase I enzymes. There
      was a significant decline in the number of tumors, tumor volume and oral squamous
      cell carcinoma in both simultaneous and post GTP treated animals relative to 4
      NQO induced animals; on comparing simultaneous and post GTP treated animals the
      number of tumors, tumor volume and oral squamous cell carcinoma was significantly
      reduced in post treated animals. Thus inhibition of Phase I enzymes could be
      attributed to the protective efficacy of GTP which deactivates carcinogen and GTP
      induced the expression of Phase II enzymes that detoxifies the 4-NQO. It can be
      proposed that GTP plays role as a detoxifying agent by which its modulating role
      prevented/inhibited the formation of tumor.

PMID- 18336808
TI  - 3D medical volume reconstruction using web services.
AB  - We address the problem of 3D medical volume reconstruction using web services.
      The use of proposed web services is motivated by the fact that the problem of 3D
      medical volume reconstruction requires significant computer resources and human
      expertise in medical and computer science areas. Web services are implemented as
      an additional layer to a dataflow framework called data to knowledge. In the
      collaboration between UIC and NCSA, pre-processed input images at NCSA are made
      accessible to medical collaborators for registration. Every time UIC medical
      collaborators inspected images and selected corresponding features for
      registration, the web service at NCSA is contacted and the registration
      processing query is executed using the image to knowledge library of registration
      methods. Co-registered frames are returned for verification by medical
      collaborators in a new window. In this paper, we present 3D volume reconstruction
      problem requirements and the architecture of the developed prototype system at
      http://isda.ncsa.uiuc.edu/MedVolume. We also explain the tradeoffs of our system
      design and provide experimental data to support our system implementation. The
      prototype system has been used for multiple 3D volume reconstructions of blood
      vessels and vasculogenic mimicry patterns in histological sections of uveal
      melanoma studied by fluorescent confocal laser scanning microscope.

PMID- 18336809
TI  - Quantification of particle deposition in asymmetrical tracheobronchial model
      geometry.
AB  - The primary objective of this study was to quantify the local inspiratory and
      expiratory aerosol deposition in a highly asymmetric five-generation
      tracheobronchial tree. User-enhanced commercial codes and self-developed software
      was used to compute the air velocity field as well as particle deposition
      distributions for a large size range of inhalable particles. The numerical model
      was validated by comparison of our results with experimental flow measurements
      and particle deposition data available in the open literature. Our simulations
      show highly localised deposition patterns for all particle sizes, but mainly for
      the larger particles. As expected, deposition efficiencies and deposition
      fractions proved to be very sensitive to the particle size. The deposition
      density in the hot spots can be hundreds and even thousand times higher than the
      mean deposition density. Present results can be of interest to researchers
      involved in the assessment of adverse health effects of inhaled aerosols or
      optimising the drug aerosol delivery into the lung.

PMID- 18336810
TI  - Effect of PPADS on achondroplasic chondrocytes: inhibition of FGF receptor type 3
      over-activity.
AB  - Achondroplasia, results from a mutation in the FGF receptor type 3, leading to
      receptor hyperactivation and subsequent amplification of FGF receptor type 3
      signals. We have tested the ability of pyridoxal-5'-phosphate-6-azophenyl-2', 4'
      disulfonate (PPADS) to decrease the overactivation and signalling of FGF receptor
      type 3 in achondroplasic chondrocytes. PPADS reduced the tyrosine phosphorylation
      of FGF receptor type 3 triggered by fibroblast growth factor 9 (FGF9) (50%
      reduction), as well as the activation of extracellular signal-regulated kinases 1
      and 2 (ERK1/2) pathway. As a consequence of this inhibitory effect on ERK1/2
      activity the loss of extracellular matrix was also reversed by PPADS. The action
      of PPADS seems to be due to a mechanism independent of P2 receptor antagonism.

PMID- 18336811
TI  - Pharmacological evaluation of LH-21, a newly discovered molecule that binds to
      cannabinoid CB1 receptor.
AB  - LH-21 (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-hexyl-1H-1,2,4-triazole) was
      previously reported as a neutral antagonist at the cannabinoid CB1 receptor
      which, despite its reported poor ability to penetrate into the brain, suppressed
      food intake and body weight in rats by intraperitoneal administration. In the
      present study, we studied the mechanism of action of LH-21 by characterizing its
      in vitro pharmacological properties and in vivo efficacy. LH-21 inhibited the
      binding of [3H]CP55940 to cloned human and rat CB1 receptors with IC50 values of
      631+/-98 nM, and 690+/-41 nM, respectively, and acted as an inverse agonist in a
      cAMP functional assay using cultured cells expressing human, rat or mouse CB1
      receptor. The compound was shown to be brain-penetrant in rats by intravenous
      administration. Importantly, a single dose of LH-21 (60 mg/kg, i.p.) caused a
      similar suppression of overnight food intake and body weight gain in wild-type
      and CB1 receptor knockout mice. Our results suggest that LH-21 is a low affinity
      inverse agonist for the CB1 receptor and does not act on the CB1 receptor to
      inhibit food intake in mice.

PMID- 18336812
TI  - Effect of co-administration of a serotonin-noradrenaline reuptake inhibitor and a
      dopamine agonist on extracellular monoamine concentrations in rats.
AB  - Recent studies have shown that dopamine agonists are useful for the treatment of
      not only Parkinson's disease, but also major depressive disorders. However, while
      these dopamine agonists provide a new treatment strategy for major depressive
      disorders, such as treatment-resistant cases, the antidepressant effect of
      dopamine agonists has yet to be investigated. To examine the mechanism of the
      antidepressive effect of dopamine agonists, we investigated the acute effect of
      the dopamine receptor agonist, cabergoline, and the serotonin-noradrenaline
      reuptake inhibitor, milnacipran, on extracellular noradrenaline, dopamine and
      serotonin concentrations in the rat medial prefrontal cortex. There was a greater
      increase in extracellular noradrenaline concentrations when acute milnacipran (30
      mg/kg intraperitoneally) was administered after acute high-dose cabergoline (1
      and 2 mg/kg subcutaneously) than when acute milnacipran was administered
      following acute vehicle or low-dose cabergoline (0.25 mg/kg subcutaneously).
      There were no significant differences noted in the dopamine or serotonin
      concentrations. These results suggest that the addition of cabergoline has the
      potential to strengthen the antidepressant effects of milnacipran and that the
      mechanism of action of the antidepressive effect of dopamine agonists might be
      due to enhancement of induced increases of extracellular noradrenaline.

PMID- 18336813
TI  - Different affinities of native alpha1B-adrenoceptors for ketanserin between
      intact tissue segments and membrane preparations.
AB  - The pharmacological profiles of alpha1-adrenoceptors for ketanserin, prazosin,
      silodosin, and BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8
      azaspiro[4,5]decane-7,9-dione dihydrochloride) were examined under different
      assay conditions. Among the tested antagonists and alpha1-adrenoceptors subtypes,
      ketanserin showed significantly lower affinity for the alpha1B-adrenoceptor
      subtype in intact tissue sampled from the rat tail artery, thoracic aorta, and
      cerebral cortex (functional pKB and binding pKi were approximately 6), than in
      cerebral cortex membrane preparations or whole cell and membrane preparations of
      alpha1B-adrenoceptor transfected human embryonic kidney 293T (HEK 293T) cells
      (pKi was approximately 8). In these tissues and cells, however, ketanserin showed
      a similar affinity (pKi = approximately 8) for alpha1A- and alpha1D-adrenoceptors
      even though the assays were conducted under different conditions. In contrast,
      the affinities of alpha1A-, alpha1B-, and alpha1D-adrenoceptors for prazosin,
      silodosin, and BMY 7378 did not significantly change under different assay
      conditions and in different tissues. The present study reveals that the
      pharmacological profiles of native alpha 1B-adrenoceptors for ketanserin is
      strongly influenced by the assay conditions and suggest that antagonist affinity
      is not necessarily constant.

PMID- 18336814
TI  - Sumoylation differentially regulates Goosecoid-mediated transcriptional
      repression.
AB  - Goosecoid (Gsc), a paired-like homeobox gene expressed in the vertebrate
      organizer, functions as a transcriptional repressor either by direct DNA binding
      to paired TAAT homeodomain sites or through recruitment by the forkhead/winged
      helix transcription factor Foxh1. Here, we report that Gsc is post
      translationally modified by small ubiquitin-like modifier proteins (SUMO).
      Members of the PIAS family of proteins enhance Gsc sumoylation and this
      modification occurs on at least six lysine residues. Stable expression of a SUMO
      defective Gsc mutant (Gsc 6Km) in MDA-MB-231 breast cancer cells results in
      morphological changes giving rise to cells with increased cell area. We
      demonstrate that Gsc 6Km can effectively repress Foxh1-mediated induction of the
      Mixl1 promoter, indicating that sumoylation is not required for Gsc-mediated
      repression of promoters where recruitment occurs through Foxh1. In contrast, Gsc
      6Km exhibits a decreased ability to repress the induction of promoters to which
      it is directly recruited through paired-homeodomain binding sites, including its
      own promoter and that of the Xenopus Brachyury gene. Taken together, our data
      suggests that regulation of Gsc repressive activity by SUMO modification is
      promoter specific and may serve to differentially regulate genes that function to
      control cell morphology during early development and cancer.

PMID- 18336815
TI  - GABA A receptors are associated with retinal ganglion cell death induced by
      oxidative stress.
AB  - A previously proteomic study from our laboratory showed that the expression of
      the protein of the GABA A receptor beta1 subunit was significantly increased in
      the retina of EAAC1-deficient (EAAC1-/-) mice, a mouse model of glaucoma. The
      purpose of this study was to investigate the role played by GABA A receptor beta1
      subunit in the death of retinal ganglion cells (RGCs) caused by oxidative stress.
      The retinal sites and expression pattern of GABA A receptor beta1 subunit were
      determined by immunohistochemistry in the retina of ICR mice. A RGC line, RGC-5,
      was exposed to GABA A receptor agonist and antagonist, and the cell viability was
      determined by the MTS assay. The effect of GABA A receptor antagonist on the
      death of RGCs, and the activation of oxidative stress signaling induced by
      hydrogen peroxide was investigated. Our results showed that the GABA A receptor
      beta1 subunit was expressed on the RGCs of ICR mice. GABA A receptor agonist
      induced RGCs death, and this death was inhibited by bicuculline, a GABA A
      receptor antagonist. The hydrogen peroxide-induced death of RGCs was reduced by
      GABA A receptor antagonist, and the oxidative stress signaling activated by
      hydrogen peroxide was also inhibited. These results indicate that GABA A
      receptors are expressed on RGCs and may play a role in the death of RGCs induced
      by oxidative stress.

PMID- 18336816
TI  - Serotonergic activation of 5HT1A and 5HT2 receptors modulates sexually dimorphic
      communication signals in the weakly electric fish Apteronotus leptorhynchus.
AB  - Serotonin modulates agonistic and reproductive behavior across vertebrate
      species. 5HT(1A) and 5HT(1B) receptors mediate many serotonergic effects on
      social behavior, but other receptors, including 5HT(2) receptors, may also
      contribute. We investigated serotonergic regulation of electrocommunication
      signals in the weakly electric fish Apteronotus leptorhynchus. During social
      interactions, these fish modulate their electric organ discharges (EODs) to
      produce signals known as chirps. Males chirp more than females and produce two
      chirp types. Males produce high-frequency chirps as courtship signals; whereas
      both sexes produce low-frequency chirps during same-sex interactions.
      Serotonergic innervation of the prepacemaker nucleus, which controls chirping, is
      more robust in females than males. Serotonin inhibits chirping and may contribute
      to sexual dimorphism and individual variation in chirping. We elicited chirps
      with EOD playbacks and pharmacologically manipulated serotonin receptors to
      determine which receptors regulated chirping. We also asked whether serotonin
      receptor activation generally modulated chirping or more specifically targeted
      particular chirp types. Agonists and antagonists of 5HT(1B/1D) receptors (CP
      94253 and GR-125743) did not affect chirping. The 5HT(1A) receptor agonist 8OH
      DPAT specifically increased production of high-frequency chirps. The 5HT(2)
      receptor agonist DOI decreased chirping. Receptor antagonists (WAY-100635 and MDL
      11939) opposed the effects of their corresponding agonists. These results suggest
      that serotonergic inhibition of chirping may be mediated by 5HT(2) receptors, but
      that serotonergic activation of 5HT(1A) receptors specifically increases the
      production of high-frequency chirps. The enhancement of chirping by 5HT(1A)
      receptors may result from interactions with cortisol and/or arginine vasotocin,
      which similarly enhance chirping and are influenced by 5HT(1A) activity in other
      systems.

PMID- 18336817
TI  - Failed Emergency Department disposition to the ward of patients with thoracic
      injury.
AB  - AIMS: To characterise patients who were admitted to the ward following Emergency
      Department (ED) management for thoracic injury yet went on to require Intensive
      Care Unit (ICU) admission. To identify risk factors for failed ward management.
      METHODS: All patients admitted to the ward following chest trauma from 2002 to
      2006 were identified from the Alfred Hospital trauma database. Patients who went
      on to require ICU admission were compared to those admitted to and discharged
      from the ward without requiring ICU. Possible predictors of ICU admission were
      analysed. RESULTS: There were 764 patients during the study period who were
      admitted to the ward following chest trauma. Of these, 70 patients went on to
      require Intensive Care admission. Patients requiring ICU admission spent a
      significantly longer time in hospital and required significantly more
      rehabilitation. Multivariate analysis using stepwise logistic regression
      confirmed intercostal catheter (ICC) insertion and higher injury severity scores
      as significant independent variables associated with ICU admission. Associated
      abdominal injury, along with multiple rib fractures and flail were also
      predictive of failed ward management. CONCLUSION: This study demonstrated that
      intercostal catheter insertion (tube thoracostomy) was an independent risk factor
      for deterioration following admission along with multiple rib fractures and
      certain associated injuries. This should be considered when admitting patients to
      the ward.

PMID- 18336818
TI  - Diagnostic laparoscopy for the evaluation of occult diaphragmatic injury
      following penetrating thoracoabdominal trauma.
AB  - BACKGROUND: Occult diaphragmatic injury following penetrating thoracoabdominal
      trauma can be difficult to diagnose. Radiographic findings are often non-specific
      or absent. Undetected injuries may remain clinically silent, only to present
      later with life-threatening complications associated with diaphragmatic
      herniation. Diagnostic laparoscopy allows for the evaluation of trauma patients
      lacking clinical indications for a formal laparotomy. The purpose of this study
      was to evaluate the incidence of occult diaphragmatic injury and investigate the
      role of laparoscopy in patients with penetrating thoracoabdominal trauma who lack
      indications for exploratory laparotomy except the potential for a diaphragmatic
      injury. METHODS: Haemodynamically stable patients with penetrating
      thoracoabdominal trauma without indications for laparotomy (haemodynamic
      instability, evisceration, or peritonitis on exam) and evaluated with diagnostic
      laparoscopy to determine the presence of a diaphragmatic injury were
      retrospectively reviewed. Thoracoabdominal wounds were defined as wounds bounded
      by the nipple line over the anterior and posterior chest superiorly and the
      costal margin inferiorly. RESULTS: One hundred and eight patients were evaluated
      for penetrating thoracoabdominal injuries (80 stabs and 28 gunshots) over the
      study period. 22 (20%) diaphragmatic injuries were identified. These were
      associated with injuries to the spleen (5), stomach (3) and liver (2). There was
      a greater incidence of haemopneumothorax (HPTX) in patients with diaphragmatic
      injury (32%) compared to those without injury (20%). 29% of patients with a HPTX
      had a diaphragmatic injury. However, 18% of patients with a normal chest
      radiograph were also found to have a diaphragmatic injury. CONCLUSIONS: The
      incidence of diaphragmatic injury associated with penetrating thoracoabdominal
      trauma is high. Clinical and radiographic findings can be unreliable for
      detecting occult diaphragmatic injury. Diagnostic laparoscopy provides a vital
      tool for detecting occult diaphragmatic injury among patients who have no other
      indications for formal laparotomy.

PMID- 18336819
TI  - Combined therapy of pentastarch, dexamethasone, and dibutyryl-cAMP or beta 2
      agonist attenuates ischaemia/reperfusion injury of rat lung.
AB  - We hypothesised that combined therapy with macromolecules that seal endothelial
      damage [pentastarch (Penta)], an anti-inflammatory agent [dexamethasone (Dex)],
      and an agent that reabsorbs alveolar fluid [beta(2)-agonist or dibutyryl-cAMP
      (Bt(2)-cAMP)] would have additive ameliorating effects on ischaemia/reperfusion
      (I/R) injury of the lung. We perfused one of the following solutions into
      isolated rat lungs in a closed circulating system, either prior to I/R injury
      (groups 1-5) or following 60 min of ischaemia (groups 6-10): (1) 0.9% normal
      saline (NS), (2) Penta, (3) Penta+Dex, (4) Penta+Bt(2)-cAMP, (5) Penta+beta(2)
      agonist inhalation, (6) Penta+Dex, (7) Penta+Bt(2)-cAMP, (8) Penta+beta(2)
      agonist inhalation, (9) Penta+Dex+Bt(2)-cAMP, or (10) Penta+Dex+beta(2)-agonist
      inhalation. Haemodynamics, lung weight gain (LWG), capillary filtration
      coefficient (K(fc)), cytokine mRNA levels, and lung pathology were assessed.
      Results showed that Dex, Bt(2)-cAMP, or beta(2)-agonist as an additive to Penta
      decreased K(fc) and LWG below values seen with Penta alone. Furthermore, LWG and
      K(fc) values in groups with three protective agents were lower than those in
      groups with two protective agents. Significantly lower levels of TNF-alpha and IL
      1 mRNAs were observed in groups treated with Dex. Histopathological studies
      showed decreased injury profiles for all combined therapy groups. We conclude
      that the addition of Dex, Bt(2)-cAMP, or beta(2)-adrenergic agonist to Penta
      solution promoted attenuation of I/R injury. Furthermore, combination therapy
      with three protective agents (Penta+Dex+beta(2)-adrenergic agonist) caused the
      greatest attenuation of I/R.

PMID- 18336820
TI  - Distraction histogenesis of an anastomosed artery.
AB  - This study examined the possibility of an adaptive reaction of anastomosed
      arteries under tension during a distraction lengthening procedure in the tibiae
      of rabbits. After an osteotomy at the mid tibia, the posterior tibial arteries
      were transected and anastomosed. Using a pair of small external fixators, the
      tibiae were distracted at a rate of 0.5mm/day (groups I-IV rabbits). Three weeks
      after 25% lengthening, the patency and histology of the arteries were examined.
      Angiography revealed that all of the anastomosed arteries were patent, and
      intimal hyperplasia was a constant finding. The mean thickness of the intima of
      the lengthened segment in group I was 60.4 microm, which is 5.0, 3.4 and 2.1
      times higher that of the controls in groups IV (un-manipulated arteries, 12.2
      microm), III (unlengthened but anastomosed arteries, 17.8 microm) and II
      (lengthened but untouched arteries, 28.7 microm), respectively. These results
      show that an anastomosed artery can maintain its patency at a certain level and
      speed of distraction lengthening. Therefore, it is possible that distraction
      lengthening and vascular anastomoses can be performed simultaneously provided
      there is careful monitoring of the circulation.

PMID- 18336821
TI  - Cervical leiomyosarcoma diagnosed after uterine artery embolization.

PMID- 18336822
TI  - Selected metabolic parameters and the risk for uterine fibroids.
AB  - OBJECTIVE: To analyze the possible association between insulin resistance and
      dyslipidemia with uterine fibroids, using objective metabolic measurements.
      METHOD: A cross-sectional study of 56 women with uterine fibroids (case group)
      and 20 women without fibroids (control group). Levels of fasting glucose,
      insulin, C-peptide, sex hormone-binding globulin, and the lipid panel were
      measured. The short insulin tolerance test was performed. Body mass index,
      atherogenic index, and the indicator of insulin resistance (Kitt) were also
      calculated. RESULTS: Women with fibroids had significantly higher levels of serum
      HDL-cholesterol compared with control patients (1.8+/-0.3 vs 1.6+/-0.5; P<0.05).
      Women with fibroids aged 30-45 years had significantly lower LDL-cholesterol
      levels than comparative control patients (2.9+/-0.7 vs 3.4+/-0.9; P<0.05). A
      positive correlation between volume of the largest fibroid and serum HDL
      cholesterol level was found in women aged 30-45 years. There were no differences
      in indicators of insulin resistance between the groups. CONCLUSION: Insulin
      resistance was not shown to be a risk factor for fibroids. There is a negative
      association between some parameters of metabolic syndrome and fibroid volume.

PMID- 18336823
TI  - Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and
      first functional analysis of the TCA cycle in Toxoplasma gondii.
AB  - The apicomplexan parasite Toxoplasma gondii displays some unusual localisations
      of carbohydrate converting enzymes, which is due to the presence of a vestigial,
      non-photosynthetic plastid, referred to as the apicoplast. It was recently
      demonstrated that the single pyruvate dehydrogenase complex (PDH) in T. gondii is
      exclusively localised inside the apicoplast but absent in the mitochondrion. This
      raises the question about expression, localisation and function of enzymes for
      the tricarboxylic acid (TCA)-cycle, which normally depends on PDH generated
      acetyl-CoA. Based on the expression and localisation of epitope-tagged fusion
      proteins, we show that all analysed TCA cycle enzymes are localised in the
      mitochondrion, including both isoforms of malate dehydrogenase. The absence of a
      cytosolic malate dehydrogenase suggests that a typical malate-aspartate shuttle
      for transfer of reduction equivalents is missing in T. gondii. We also localised
      various enzymes which catalyse the irreversible steps in gluconeogenesis to a
      cellular compartment and examined mRNA expression levels for gluconeogenesis and
      TCA cycle genes between tachyzoites and in vitro bradyzoites. In order to get
      functional information on the TCA cycle for the parasite energy metabolism, we
      created a conditional knock-out mutant for the succinyl-CoA synthetase.
      Disruption of the sixth step in the TCA cycle should leave the biosynthetic parts
      of the cycle intact, but prevent FADH2 production. The succinyl-CoA synthetase
      depletion mutant displayed a 30% reduction in growth rate, which could be
      restored by supplementation with 2 microM succinate in the tissue culture medium.
      The mitochondrial membrane potential in these parasites was found to be
      unaltered. The lack of a more severe phenotype suggests that a functional TCA
      cycle is not essential for T. gondii replication and for maintenance of the
      mitochondrial membrane potential.

PMID- 18336824
TI  - Genetic variants within the interleukin-1 gene cluster, and risk of incident
      myocardial infarction, and ischemic stroke: a nested case-control approach.
AB  - BACKGROUND AND PURPOSE: Recent findings implicating specific gene polymorphisms
      of the interleukin-1 superfamily gene cluster in the risk of developing athero
      thrombotic disorders have generated great interest. However, to date, no
      prospective, genetic-epidemiological data are available. METHODS: Using DNA
      samples collected at baseline in a prospective cohort of 14,916 initially healthy
      American men, we evaluated seven gene polymorphisms within the interleukin-1 gene
      cluster among 599 individuals who subsequently developed athero-thrombotic event
      and among 599 age- and smoking-matched individuals who remained free of reported
      cardiovascular disease during follow-up (341 incident myocardial infarction
      matched case-control pairs and 258 incident ischemic stroke matched case-control
      pairs). RESULTS: Overall, we observed little evidence of association between the
      polymorphisms tested and risk of incident athero-thrombotic events. Further
      adjustment for traditional cardiovascular risk factors yielded similar null
      findings. Of note, a modest association of rs1143623 with reduced risk of
      incident MI was found (recessive model: OR=0.455, 95% CI=0.215-0.960, uncorrected
      p=0.039). However, this finding was not corrected for multiple testing, and thus
      requires cautious interpretation. CONCLUSION: In contrast to prior retrospective
      studies, our prospective data suggest that the IL-1 cluster gene variation is not
      associated with risk of athero-thrombotic disorders.

PMID- 18336825
TI  - Elevated serum neopterin levels and adverse cardiac events at 6 months follow-up
      in Mediterranean patients with non-ST-segment elevation acute coronary syndrome.
AB  - BACKGROUND: Little information exists regarding the prognostic role of biomarkers
      of inflammation in Mediterranean patients. High C-reactive protein and neopterin
      levels - a marker of macrophage activation - predict cardiovascular events in
      stable angina patients and patients with acute coronary syndromes (ACS). We
      sought to assess whether plasma neopterin levels predict adverse clinical
      outcomes in Mediterranean patients with non-ST elevation (NSTE) ACS, i.e.
      unstable angina (UA) and NSTE myocardial infarction (MI). METHODS: We
      prospectively assessed 397 patients (74% men) admitted with NSTEACS, 147 (37%)
      had unstable angina and 250 (63%) NSTEMI. Blood samples for neopterin and CRP
      assessment were obtained at admission. The study endpoint was the composite of
      cardiac death, acute myocardial infarction and unstable angina at 180 days.
      RESULTS: Baseline neopterin concentrations (nmol/L) were similar in unstable
      angina and NSTEMI patients (8.3 [6.6-10.7] vs. 7.9 [6.2-10.9]; p=0.4). Fifty-nine
      patients (14.9%) had events during follow-up. Twenty-nine (21.5%) patients with
      neopterin levels in the highest third experienced the combined endpoint, compared
      to 30 (11.5%) patients with neopterin levels in the second and the lowest thirds
      (log-rank 7.435, p=0.024). On multivariable hazard Cox regression, neopterin
      (highest vs. 1st and 2nd thirds, HR 1.762, 95% CI [1.023-3.036]) was
      independently associated with the combined endpoint. CONCLUSION: Increased
      neopterin levels are an independent predictor of 180-day adverse cardiac events
      in Mediterranean patients with NSTEACS.

PMID- 18336826
TI  - Implementations of two-dimensional liquid chromatography.
AB  - Today scientists must deal with complex samples that either cannot be adequately
      separated using one-dimensional chromatography or that require an inordinate
      amount of time for separation. For these cases we need two-dimensional
      chromatography because it takes far less time to generate a peak capacity n(c)
      twice in a row than to generate a peak capacity n(c)(2) once. Liquid
      chromatography has been carried out successfully on thin layers of adsorbents and
      along tubes filled with various adsorbents. The first type of separation sorts
      out the sample components in a physical separation space that is the layer of
      packing material. The analysis time is the same for all the components of the
      sample while their migration distance increases with decreasing retention. The
      resolution between two components having a certain separation factor (alpha)
      increases with increasing migration distance, i.e., from the strongly to the
      weakly retained compounds. In the second type of separation, the sample
      components are eluted from the column and separated in the time space, their
      migration distances are all the same while their retention times increase from
      the unretained to the strongly retained compounds. Separation efficiency varies
      little with retention, as long as the components are eluted from the column. We
      call these two types of separation the chromatographic separations in space
      (LC(x)) and the chromatographic separations in time (LC(t)), respectively. In
      principle, there are four ways to combine these two modes and do two-dimensional
      chromatographic separations, LC(t)xLC(t), LC(x)xLC(t), LC(t)xLC(x), and
      LC(x)xLC(x). We review, discuss and compare the potential performance of these
      combinations, their advantages, drawbacks, problems, perspectives and results.
      Currently, column-based combinations (LC(t)xLC(t)) are the most actively pursued.
      We suggest that the combination LC(x)xLC(t) shows exceptional promise because it
      permits the simultaneous second-dimension separations of all the fractions
      separated in the first-dimension, thus providing remarkable time saving.

PMID- 18336827
TI  - Enantiomeric resolution of bupivacaine by high-performance liquid chromatography
      and chiroptical detection.
AB  - This work reports a new analytical procedure for the separation and determination
      of the enantiomers of bupivacaine and the determination of the enantiomeric
      purity. The isomers were separated using a Chirex 3020 (250 mm x 4.6 mm) with a
      mobile phase of n-hexane:dichloroethane:ethanol (82:9:9, v/v/v) at a flow-rate of
      1 ml min(-1) and UV, polarimetric and circular dichroism (CD) detection. Obtained
      retention times were 5.93 and 7.53 min (R and S) with a resolution of Rs=2.36.
      Precisions (RSD) were 1.83 and 2.02% (CD detection) and 3.07 and 1.26% (UV
      detection) for R- and S-enantiomers, respectively (at 10 microg level). Detection
      limits were 0.5 and 0.5 microg (R and S) with CD detection, and 0.9 and 0.3
      microg with UV detection. Polarimetric detection was inadequate to perform a
      quantitative method at similar concentration ranges as UV and CD because of poor
      sensitivity. A procedure for determination of enantiomeric purity using a
      conventional chromatographic column (RP18, Luna) coupled to a CD detector and
      anisotropy factor (CD/UV) as analytical signal was also developed. Obtained
      results show that RSDs of 6.7-1.6% were obtained in the range of 0-100%
      enantiomeric purity.

PMID- 18336828
TI  - Histopathological standards for the diagnosis of gastrointestinal inflammation in
      endoscopic biopsy samples from the dog and cat: a report from the World Small
      Animal Veterinary Association Gastrointestinal Standardization Group.
AB  - The characterization of inflammatory change in endoscopic biopsy samples of the
      gastrointestinal mucosa is an increasingly important component in the diagnosis
      and management of canine and feline gastrointestinal disease. Interpretation has
      hitherto been limited by the lack of standard criteria that define morphological
      and inflammatory features, and the absence of such standardization has made it
      difficult, if not impossible, to compare results of retrospective or prospective
      studies. The World Small Animal Veterinary Association (WSAVA) Gastrointestinal
      Standardization Group was established, in part, to develop endoscopic and
      microscopical standards in small animal gastroenterology. This monograph presents
      a standardized pictorial and textual template of the major histopathological
      changes that occur in inflammatory disease of the canine and feline gastric body,
      gastric antrum, duodenum and colon. Additionally, a series of standard
      histopathological reporting forms is proposed, to encourage evaluation of biopsy
      samples in a systematic fashion. The Standardization Group believes that the
      international acceptance of these standard templates will advance the study of
      gastrointestinal disease in individual small companion animals as well as
      investigations that compare populations of animals.

PMID- 18336829
TI  - Preliminary observations on the experimental transmission of chronic wasting
      disease (CWD) from elk and white-tailed deer to fallow deer.
AB  - To determine the transmissibility of chronic wasting disease (CWD) to fallow deer
      (Dama dama) and to provide information about clinical course, lesions and
      suitability of currently used diagnostic procedures for detection of CWD in this
      species, 13 fawns were inoculated intracerebrally with CWD brain suspension from
      elk (n=6) or white-tailed deer (n=7). Three other fawns were kept as uninfected
      controls. Three CWD-inoculated deer were killed 7.6 months post-inoculation
      (mpi). None had abnormal prion protein (PrPd) in their tissues. One sick deer
      died at 24 mpi and one deer without clinical signs was killed at 26 mpi. Both
      animals had a small focal accumulation of PrPd in the midbrain. Between 29 and 37
      mpi, three other deer became sick and were killed. All had shown gradual decrease
      in appetite and some loss of body weight. Microscopical lesions of spongiform
      encephalopathy were not observed, but PrPd was detected in tissues of the central
      nervous system (CNS) by immunohistochemistry, western blot and by two
      commercially available rapid diagnostic tests. This study demonstrates that
      intracerebrally inoculated fallow deer amplified CWD PrPd from white-tailed deer
      and elk in the absence of lesions of spongiform encephalopathy. Four years after
      CWD inoculation, the remaining five inoculated and two control deer are alive and
      apparently healthy.

PMID- 18336830
TI  - Interfascicular concealment at the beginning of atrioventricular node reentrant
      tachycardia.

PMID- 18336831
TI  - Incomplete electrical isolation of sex-pheromone responsive olfactory receptor
      neurons from neighboring sensilla.
AB  - In the long trichoid sensilla on male Helicoverpa zea antennae, approximately 40%
      of the sensilla having a large-spiking olfactory receptor neuron responding to
      the major pheromone component, (Z)-11-hexadecenal, also exhibit small-spiking
      action potentials that also seem to be responsive to this same compound. In this
      study, we investigated whether these small-spiking signals are a result of
      intrusive electrical signals generated from neighboring sensilla. Two methods
      were used for this study. First, the sensillum was completely covered by the
      saline-filled recording electrode to physically prevent the sensillum from being
      contacted by exposure to (Z)-11-hexadecenal. In this case, activation of the
      large-spiking neuron in response to the pheromone component was prevented,
      whereas the small-spiking activity continued to be influenced by the airborne
      delivery of the pheromone. In the second method the (Z)-11-hexadecenal was
      applied directly in solution through the cut tip of the sensillum through the
      recording electrode. In this case only large-spiking activity occurred in
      response to (Z)-11-hexadecenal, with no increase whatsoever in the firing
      frequency of the small spikes. We conclude that these long trichoid olfactory
      sensilla are not completely isolated electrically from neighboring sensilla and
      that small spikes in some recordings originate from large-spiking olfactory
      receptor neurons (ORNs) in neighboring sensilla.

PMID- 18336832
TI  - Quantifying the reproduction of Bacillus thuringiensis HD1 in cadavers and live
      larvae of Plutella xylostella.
AB  - The Bacillus cereus group comprises a range of micro-organisms with diverse
      habits, including gut commensals, opportunistic pathogens and soil saprophytes.
      Using quantitative microbiological methods we tested whether Bacillus
      thuringiensis (Bt) could reproduce in cadavers of Plutella xylostella killed by
      Bt, or in the gut of live insects, or be transmitted vertically from females to
      their offspring. We also tested whether diverse Bt strains could grow in high
      nutrient broth at a pH similar to that in the larval midgut. Low levels of
      reproduction were found in insect cadavers but there was no evidence of vertical
      transmission, or of significant reproduction in live insects. Four strains of B.
      thuringiensis var. kurstaki and one of B. thuringiensis var. tenebrionis were
      found to be capable of growth at high pH. Greater spore recovery rates in frass
      were found in hosts that were resistant or tolerant of infection. We concluded
      that that spores recovered in frass represent, in general, an ungerminated
      fraction of ingested inoculum and that germination rates are reduced in
      unsuitable hosts.

PMID- 18336833
TI  - Molecular aspects of the congenital and acquired Long QT Syndrome: clinical
      implications.
AB  - The Long QT Syndrome (LQTS) is a complex and multi-factorial disorder that
      predisposes to life-threatening ventricular arrhythmias. Both hereditary and
      acquired subforms have been identified over the years. Recently, it has become
      clear that the interaction of multiple acquired and genetic aetiologic factors
      (e.g. disease modifiers) play an important role in differentiating genotype into
      a continuous spectrum of clinical or subclinical phenotypes. The genotype
      phenotype correlation thereby remains very unpredictable in asymptomatic
      patients, raising important concerns for clinical practice and also for drug
      development. Therefore, this review aims at providing a comprehensive overview on
      LQTS highlighting the molecular mechanisms of arrhythmogenesis involved in both
      the hereditary and the acquired subtypes of the disorder. From this perspective
      this manuscript then focuses on how the genotype translates into phenotype. A
      logical overview is provided with the multitude of hereditary and acquired
      factors that are involved and of the complexity of the interactions that
      ultimately result in the heterogeneous expressivity and the unpredictability of
      the phenotype. Based on recent basic and clinical data this review further aims
      at providing an update on the clinical properties and management of LQT patients
      including diagnostic work-up and therapy.

PMID- 18336834
TI  - Modeling the in vitro 20S proteasome activity: the effect of PA28-alphabeta and
      of the sequence and length of polypeptides on the degradation kinetics.
AB  - Proteasomes are fundamental for the degradation of intracellular proteins, having
      a key role in several important metabolic and signaling pathways, in the cell
      cycle and in antigen presentation. In vitro proteasomal digestion assays are
      widely used in molecular biology and immunology. We developed a model, ProteaMAlg
      (proteasome modeling algorithm) that describes the kinetics of specific protein
      fragments generated by 20S proteasomes in different conditions, once the
      substrate cleavage strengths are provided. ProteaMAlg was tested on a variety of
      data available in the literature as well as on new degradation experiments
      performed with polypeptides of different sequences and lengths. The comparison
      between in vitro and in silico experiments was used to quantify the effect on
      degradation of the sequence and the length of target polypeptides, of the
      presence of regulatory molecules such as PA28-alphabeta, and of the type of 20S
      proteasome (constitutive- or immunoproteasome). The model showed that the effect
      of the PA28 regulatory subunit results in a modification of the gating functions
      of the proteasome core particle. Immunoproteasome digestion experiments suggested
      that this form of proteasome, which is involved in generating MHC-class I
      epitopes, presents modified cleavage and gating activities. Our analysis improves
      the current understanding of the kinetics of proteasome functioning, and provides
      a tool to quantify and predict the effect of key parameters during in vitro
      digestion. ProteaMAlg is publicly available on the web
      (http://www.proteamalg.com).

PMID- 18336836
TI  - The intrinsic contributions of tyrosine, serine, glycine and arginine to the
      affinity and specificity of antibodies.
AB  - Synthetic antibody libraries with restricted chemical diversity were used to
      explore the intrinsic contributions of four amino acids (Tyr, Ser, Gly and Arg)
      to the affinity and specificity of antigen recognition. There was no correlation
      between nonspecific binding and the content of Tyr, Ser or Gly in the antigen
      binding site, and in fact, the most specific antibodies were those with the
      highest Tyr content. In contrast, Arg content was clearly correlated with
      increased nonspecific binding. We combined Tyr, Ser and Gly to generate highly
      specific synthetic antibodies with affinities in the subnanomolar range, showing
      that the high abundance of Tyr, Ser and Gly in natural antibody germ line
      sequences reflects the intrinsic capacity of these residues to work together to
      mediate antigen recognition. Despite being a major functional contributor to co
      evolved protein-protein interfaces, we find that Arg does not contribute
      generally to the affinity of naive antigen-binding sites and is detrimental to
      specificity. Again, this is consistent with studies of natural antibodies, which
      have shown that nonspecific, self-reactive antibodies are rich in Arg and other
      positively charged residues. Our findings suggest that the principles governing
      naive molecular recognition differ from those governing co-evolved interactions.
      Analogous studies can be designed to explore the roles of the other amino acids
      in molecular recognition. Results of such studies should illuminate the basic
      principles underlying natural protein-protein interactions and should aid the
      design of synthetic binding proteins with functions beyond the scope of natural
      proteins.

PMID- 18336835
TI  - Dynamics of Recognition between tRNA and elongation factor Tu.
AB  - Elongation factor Tu (EF-Tu) binds to all standard aminoacyl transfer RNAs (aa
      tRNAs) and transports them to the ribosome while protecting the ester linkage
      between the tRNA and its cognate amino acid. We use molecular dynamics
      simulations to investigate the dynamics of the EF-Tu.guanosine 5'-triphosphate.aa
      tRNA(Cys) complex and the roles played by Mg2+ ions and modified nucleosides on
      the free energy of protein.RNA binding. Individual modified nucleosides have
      pronounced effects on the structural dynamics of tRNA and the EF-Tu.Cys-tRNA(Cys)
      interface. Combined energetic and evolutionary analyses identify the coevolution
      of residues in EF-Tu and aa-tRNAs at the binding interface. Highly conserved EF
      Tu residues are responsible for both attracting aa-tRNAs as well as providing
      nearby nonbonded repulsive energies that help fine-tune molecular attraction at
      the binding interface. In addition to the 3' CCA end, highly conserved tRNA
      nucleotides G1, G52, G53, and U54 contribute significantly to EF-Tu binding
      energies. Modification of U54 to thymine affects the structure of the tRNA common
      loop resulting in a change in binding interface contacts. In addition, other
      nucleotides, conserved within certain tRNA specificities, may be responsible for
      tuning aa-tRNA binding to EF-Tu. The trend in EF-Tu.Cys-tRNA(Cys) binding
      energies observed as the result of mutating the tRNA agrees with experimental
      observation. We also predict variations in binding free energies upon
      misacylation of tRNA(Cys) with d-cysteine or O-phosphoserine and upon changing
      the protonation state of l-cysteine. Principal components analysis in each case
      reveals changes in the communication network across the protein.tRNA interface
      and is the basis for the entropy calculations.

PMID- 18336837
TI  - The crystal structure of beta-alanine synthase from Drosophila melanogaster
      reveals a homooctameric helical turn-like assembly.
AB  - Beta-alanine synthase (betaAS) is the third enzyme in the reductive pyrimidine
      catabolic pathway, which is responsible for the breakdown of the nucleotide bases
      uracil and thymine in higher organisms. It catalyzes the hydrolysis of N-carbamyl
      beta-alanine and N-carbamyl-beta-aminoisobutyrate to the corresponding beta-amino
      acids. betaASs are grouped into two phylogenetically unrelated subfamilies, a
      general eukaryote one and a fungal one. To reveal the molecular architecture and
      understand the catalytic mechanism of the general eukaryote betaAS subfamily, we
      determined the crystal structure of Drosophila melanogaster betaAS to 2.8 A
      resolution. It shows a homooctameric assembly of the enzyme in the shape of a
      left-handed helical turn, in which tightly packed dimeric units are related by 2
      fold symmetry. Such an assembly would allow formation of higher oligomers by
      attachment of additional dimers on both ends. The subunit has a nitrilase-like
      fold and consists of a central beta-sandwich with a layer of alpha-helices packed
      against both sides. However, the core fold of the nitrilase superfamily enzymes
      is extended in D. melanogaster betaAS by addition of several secondary structure
      elements at the N-terminus. The active site can be accessed from the solvent by a
      narrow channel and contains the triad of catalytic residues (Cys, Glu, and Lys)
      conserved in nitrilase-like enzymes.

PMID- 18336838
TI  - Neural correlates of cognitive fatigue in multiple sclerosis using functional
      MRI.
AB  - Although fatigue is one of the major symptoms of persons with multiple sclerosis
      (MS), the behavioral and neural correlates are poorly understood. The present
      study utilized a novel approach to cognitive fatigue examining objective
      behavioral performance while simultaneously monitoring brain activity using fMRI.
      Fifteen persons with MS and 15 healthy controls were given 4 trials of a
      behavioral task assessing processing speed (mSDMT) during fMRI acquisition. It
      was hypothesized that individuals with MS would show an abnormal pattern of
      activity across time in specific brain areas previously hypothesized to subserve
      fatigue [Chaudhuri A, Behan PO. Fatigue and basal ganglia. J Neurol Sci
      2000;179:34-42]. Specifically, it was hypothesized that persons with MS would
      show a greater increase in cerebral activation across time during behavioral
      performance than that seen in healthy controls, which was interpreted as fatigue.
      No difference in performance accuracy on the mSDMT was observed, although the MS
      group was significantly slower than controls. Behavioral alterations indicative
      of fatigue in the MS group were associated with increased activation in the basal
      ganglia, frontal areas including superior, medial, middle and inferior regions,
      parietal regions (precuneus and cuneus), thalamus and the occipital lobes. These
      data provide direct support for the Chaudhuri and Behan model of "central"
      fatigue which hypothesizes a specific role of the "non-motor" functions of the
      basal ganglia.

PMID- 18336839
TI  - Intracortical inhibition and facilitation with unilateral dominant, unilateral
      nondominant and bilateral movement tasks in left- and right-handed adults.
AB  - PURPOSE: To investigate intracortical inhibition and facilitation in response to
      unilateral dominant, nondominant and bilateral biceps activation and short-term
      upper extremity training in right- and left-handed adults. METHODS: Paired-pulse
      transcranial magnetic stimulation was used to measure intracortical excitability
      in motor dominant and nondominant cortices of 26 nondisabled adults. Neural
      facilitation and inhibition were measured in each hemisphere during unilateral
      dominant, nondominant and bilateral arm activation and after training in each
      condition. RESULTS: No differences were seen between right- and left-handed
      subjects. Intracortical facilitation and decreased inhibition were seen in each
      hemisphere with unilateral activation/training of contralateral muscles and
      bilateral muscle activation/training. Persistent intracortical inhibition was
      seen in each hemisphere with ipsilateral muscle activation/training. Inhibition
      was greater in the nondominant hemisphere during dominant hemisphere activation
      (dominant arm contraction). CONCLUSION: Strongly dominant individuals show no
      difference in intracortical responses given handedness. Intracortical activity
      with unilateral and bilateral arm activation and short-term training differs
      based on hemispheric dominance, with the motor dominant hemisphere exerting a
      larger inhibitory influence over the nondominant hemisphere. Bilateral activation
      and training have a disinhibitory effect in both dominant and nondominant
      hemispheres.

PMID- 18336840
TI  - The effects of aerobic exercise training on the age-related lipid peroxidation,
      Schwann cell apoptosis and ultrastructural changes in the sciatic nerve of rats.
AB  - The potential role of exercise in preventing the age-related spontaneous
      peripheral neuropathy has not been studied. We examined the effects of long-term
      aerobic exercise training on lipid peroxidation, Schwann cell (SC) apoptosis and
      ultrastructural changes in the sciatic nerve of rats during aging. Three groups
      of 12-week old Wistar rats ran on a treadmill for 6, 9 and 12 months (exercise
      trained (ET) group, n=10 each) according to an exercise training program targeted
      at a speed of 22 m/min (at 7 degrees incline), 60 min/day, 6 days/week. Three
      corresponding groups of untrained rats were used as the controls (sedentary (SED)
      group). At the end of each period, sciatic nerve biopsies were performed, and
      processed for biochemical, immunohistochemical and ultrastructural analyses. The
      results showed that aging was associated with an increased level of nerve
      malondialdehyde (MDA, marker of lipid peroxidation) and a higher number of SC
      apoptosis in SED group. The SED group showed irregular nerve fibers with thin
      myelin sheaths and areas of myelin-axon detachment. However, the ET group had
      significantly diminished nerve lipid peroxidation and SC apoptosis. In the ET
      group, nerve fibers had a thick myelin sheath with frequent folding. These
      findings suggest that aerobic exercise training protects peripheral nerves by
      attenuating oxidative reactions, and preserving SCs and myelin sheath from
      pathologic changes, which occur during normal aging.

PMID- 18336841
TI  - Bombesin marine toxin conjugates inhibit the growth of lung cancer cells.
AB  - Hemiasterlin (Hem) and dolastatin (Dol) are marine natural products which are
      cytotoxic for cancer cells. Hem, a tripeptide, and Dol, a hexapeptide, were
      conjugated with linkers (L) to the universal BB agonist DPhe-Gln-Trp-Ala-Val
      betaAla-His-Phe-Nle-NH2(BA1) and the effects of the Hem-BB and Dol-BB conjugates
      investigated on NCI-H1299 lung cancer cells. Hem-LA-BA1 and Hem-LB-BA1 inhibited
      specific (125I-Tyr4)BB binding to NCI-H1299 cells, which have BB2 receptors (R),
      with IC50 values of 15 and 25 nM, respectively. Addition of Hem-LA-BA1 and Hem-LB
      BA1 to Fura-2 AM loaded cells containing BB2R, caused elevated cytosolic Ca2+. In
      a growth assay, Hem-LA-BA1 and Hem-LB-BA1 inhibited the proliferation of NCI
      H1299 cells. Dol-succinamide (Dols)-LD-BA1 and Dols-LE-BA1 bound with high
      affinity to NCI-H1299 cells and elevated cytosolic Ca2+, but did not inhibit the
      proliferation of NCI-H1299 cells. Also, Hem-LA-BA1 inhibited 125I-DTyr-Gln-Trp
      Ala-Val-betaAla-His-Phe-Nle-NH2 (BA2) binding to Balb/3T3 cells transfected with
      BB1R or BB2R as well as with BRS-3 with IC50 values of 130, 8, and 540 nM,
      respectively. These results show that Hem-BB conjugates are cytotoxic for cancer
      cells containing BB2R.

PMID- 18336842
TI  - Aspects of the usefulness of five marine pollution biomarkers, with emphasis on
      MN and lipid content.
AB  - By using cellular biomarkers, such as the formation of the micronucleus, the
      morphometric alterations of lipids and the morphometric changes in the lysosomal
      system, we investigated effects of experimental exposure to phenanthrene, Cu, Cd,
      and Hg for 15 days in mussels. Concerning micronuclei, the evaluation of the
      total nuclear abnormalities, instead of the micronucleus only, as a biomarker of
      marine pollution, indicated more statistically significant differences between
      the control and the pollutant treated groups. Contrary to the existing knowledge
      showing that there is an increase in lipid content after pollutant exposure, our
      results showed that there was a decrease in the amount of lipid, as well as an
      increase in the number of neutral lipids. Furthermore, although prior studies
      found that fewer lysosomes formed after pollutant exposure, this was not
      confirmed by our work, as pollutant treated animals exhibited a decrease in the
      volume and an increase in the numerical density of lysosomes, compared to control
      groups.

PMID- 18336843
TI  - Tumor necrosis factor-alpha potentiates genotoxic effects of benzo[a]pyrene in
      rat liver epithelial cells through upregulation of cytochrome P450 1B1
      expression.
AB  - Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant, which may
      contribute to the development of human cancer. The ultimate carcinogenic BaP
      metabolite produced by cytochrome P450 enzymes (CYP), such as CYP1A1 and CYP1B1,
      anti-BaP-7,8-diol-9,10-epoxide, binds covalently to DNA and causes mutations. The
      levels of various CYP isoforms can be significantly modulated under inflammatory
      conditions. As the chronic inflammation is known to contribute to carcinogenesis,
      we investigated interactions of a major proinflammatory cytokine, tumor necrosis
      factor-alpha (TNF-alpha), and BaP in regulation of the expression of CYP1A1/1B1
      and induction of DNA damage in rat liver epithelial WB-F344 cells. TNF-alpha
      enhanced induction of CYP1B1, while it simultaneously suppressed the BaP-induced
      CYP1A1 expression. The observed deregulation of CYP1 induction was found to be
      associated with a significantly enhanced formation of DNA adducts. The elevated
      DNA damage corresponded with increased phosphorylation of p53 tumor suppressor at
      Ser-15 residue, enhanced accumulation of cells in the S-phase of cell cycle and
      potentiation of BaP-induced apoptosis. Inhibition of CYP1B1 by fluoranthene
      significantly decreased both the formation of DNA adducts and the induction of
      apoptosis in WB-F344 cells treated with BaP and TNF-alpha, thus suggesting that
      this isoform might be responsible for genotoxic effects of BaP in nonparenchymal
      liver cells. Our results seem to indicate that inflammatory conditions might
      enhance genotoxic effects of carcinogenic polycyclic aromatic hydrocarbons
      through upregulation of CYP1B1 expression.

PMID- 18336844
TI  - Differential response of human and rat epoxide hydrolase to polycyclic aromatic
      hydrocarbon exposure: studies using precision-cut tissue slices.
AB  - The potential of polycyclic aromatic hydrocarbons (PAHs) to modulate microsomal
      epoxide hydrolase activity, determined using benzo[a]pyrene 5-oxide as substrate,
      in human liver, was evaluated and compared to rat liver. Precision-cut liver
      slices prepared from fresh human liver were incubated with six structurally
      diverse PAHs, at a range of concentrations, for 24h. Of the six PAHs studied,
      benzo[a]pyrene, dibenzo[a,h]anthracene and fluoranthene gave rise to a
      statistically significant increase in epoxide hydrolase activity, which was
      accompanied by a concomitant increase in epoxide hydrolase protein levels
      determined by immunoblotting. The other PAHs studied, namely dibenzo[a,l]pyrene,
      benzo[b]fluoranthene and 1-methylphenanthrene, influenced neither activity nor
      enzyme protein levels. When rat slices were incubated under identical conditions,
      only benzo[a]pyrene and dibenzo[a,h]anthracene elevated epoxide hydrolase
      activity, which was, once again accompanied by a rise in protein levels. At the
      mRNA level, however, all six PAHs caused an increase, albeit to different extent.
      In rat, epoxide hydroxylase activity in lung slices was much lower than in liver
      slices. In lung slices, epoxide hydrolase activity was elevated following
      exposure to benzo[a]pyrene and dibenzo[a,l]pyrene and, to a lesser extent, 1
      methylphenanthrene; similar observations were made at the protein level. At both
      activity and protein levels extent of induction was far more pronounced in the
      lung compared with the liver. It is concluded that epoxide hydrolase activity is
      an inducible enzyme by PAHs, in both human and rat liver, but induction potential
      by individual PAHs varies enormously, depending on the nature of the compound
      involved. Marked tissue differences in the nature of PAHs stimulating activity in
      rat lung and liver were noted. Although in the rat basal lung epoxide hydrolase
      activity is much lower than liver, it is more markedly inducible by PAHs.

PMID- 18336845
TI  - Transcriptional profiles of benzo(a)pyrene exposure in normal human mammary
      epithelial cells in the absence or presence of chlorophyllin.
AB  - Benzo(a)pyrene (BP) exposure causes alterations in gene expression in normal
      human mammary epithelial cells (NHMECs). This study used Affymetrix Hu-Gene133A
      arrays, with 14,500 genes represented, to evaluate modulation of BP-induced gene
      expression by chlorophyllin in six NHMEC strains derived from different donors. A
      major goal was to seek potential biomarkers of carcinogen exposure and how they
      behave in the presence of a chemopreventive agent. NHMECs (passage 6 and 70%
      confluence) were exposed for 24h to either vehicle control, or BP, or
      chlorophyllin followed by BP and chlorophyllin together. BP exposure resulted in
      approximately 3-fold altered expression of 49 genes in at least one of the six
      NHMEC strains. When cells were exposed to chlorophyllin pre-treatment followed by
      BP plus chlorophyllin, expression of 125 genes was similarly altered. Genes in
      the functional categories of xenobiotic metabolism, cell signaling, cell
      motility, cell proliferation, cellular transcription, metabolism, cell cycle
      control, apoptosis and DNA repair were identified. Only CYP1B1 and ALDH1A3 were
      consistently up-regulated by approximately 3-fold in most of the cell strains (at
      least 4) when exposed to BP. Cluster analysis identified a suite of 13 genes
      induced by BP where induction was mitigated in the presence of chlorophyllin.
      Additionally, cluster analysis identified a suite of 16 genes down-regulated by
      BP where induction was partially restored in the presence of chlorophyllin.

PMID- 18336846
TI  - Characterization of aconitine-induced block of delayed rectifier K+ current in
      differentiated NG108-15 neuronal cells.
AB  - The effects of aconitine (ACO), a highly toxic alkaloid, on ion currents in
      differentiated NG108-15 neuronal cells were investigated in this study. ACO (0.3
      30 microM) suppressed the amplitude of delayed rectifier K+ current (I K(DR)) in
      a concentration-dependent manner with an IC50 value of 3.1 microM. The presence
      of ACO enhanced the rate and extent of I K(DR) inactivation, although it had no
      effect on the initial activation phase of I K(DR). It could shift the
      inactivation curve of I K(DR) to a hyperpolarized potential with no change in the
      slope factor. Cumulative inactivation for I K(DR) was also enhanced by ACO.
      Orphenadrine (30 microM) or methyllycaconitine (30 microM) slightly suppressed I
      K(DR) without modifying current decay. ACO (10 microM) had an inhibitory effect
      on voltage-dependent Na+ current (I Na). Under current-clamp recordings, ACO
      increased the firing and widening of action potentials in these cells. With the
      aid of the minimal binding scheme, the ACO actions on I K(DR) was quantitatively
      provided with a dissociation constant of 0.6 microM. A modeled cell was designed
      to duplicate its inhibitory effect on spontaneous pacemaking. ACO also blocked I
      K(DR) in neuroblastoma SH-SY5Y cells. Taken together, the experimental data and
      simulations show that ACO can block delayed rectifier K+ channels of neurons in a
      concentration- and state-dependent manner. Changes in action potentials induced
      by ACO in neurons in vivo can be explained mainly by its blocking actions on I
      K(DR) and I Na.

PMID- 18336847
TI  - Lateralized contribution of prefrontal cortex in controlling task-irrelevant
      information during verbal and spatial working memory tasks: rTMS evidence.
AB  - The functional organization of working memory (WM) in the human prefrontal cortex
      remains unclear. The present study used repetitive transcranial magnetic
      stimulation (rTMS) to clarify the role of the dorsolateral prefrontal cortex
      (dlPFC) both in the types of information (verbal vs. spatial), and the types of
      processes (maintenance vs. manipulation). Subjects performed three independent
      experiments (1-back and 2-back tasks) while rTMS was applied over dlPFC for 500
      ms in the last period of the delay. In two experiments (1 and 2) physically
      identical stimuli (letters shown at different locations on a screen) under
      different domain conditions (letters or locations) were employed. Under these
      conditions, we discovered a double dissociation only in the 2-back task: during
      the letter condition, when applied to the right dlPFC, rTMS significantly delayed
      task performance, whereas, the same result was present during the location
      condition, but only when rTMS was applied to the left dlPFC. The other 2-back
      task (experiment 3), in which we had eliminated the task-irrelevant information
      (i.e. we used stimuli that varied only in one domain), did not show significant
      results. We propose that the functional dichotomy of the hemispheres may be due
      to mechanisms of cognitive control on interference, which resolve conflict
      through the inhibition of task-irrelevant information only during high WM load.
      In conclusion, these findings confirm the role of dlPFC in implementing top-down
      attentional control, and provide evidence for the theoretical suggestion that
      working memory serves to control selective attention in the normal human brain.

PMID- 18336848
TI  - Euodionosides A-G: megastigmane glucosides from leaves of Euodia meliaefolia.
AB  - From a 1-BuOH-soluble fraction of the MeOH extract of leaves of Euodia
      meliaefolia, collected in Okinawa, seven megastigmane glucosides, named
      euodionosides A-G, were isolated together with three known megastgmane
      glucosides, and two aliphatic and three phenolic compounds. Their structures were
      elucidated through a combination of spectroscopic analyses and application of the
      modified Mosher's method.

PMID- 18336849
TI  - Study of equid herpesviruses 2 and 5 in Iceland with a type-specific polymerase
      chain reaction.
AB  - The horse population in Iceland is a special breed, isolated from other horses
      for at least 1000 years. This provides an exceptional opportunity to investigate
      old and new pathogens in an inbred herd with few infectious diseases. We have
      developed a high sensitivity semi-nested PCR to study equid gammaherpesviruses 2
      and 5 (EHV-2 and 5) in Iceland. The first PCR is group specific, the second type
      specific, targeting a 113bp sequence in the glyB gene. DNA isolated from white
      blood cells and 18 different organs was tested for the presence of EHV-2 and 5.
      This was done in adult horses and foals, healthy and with various enteric
      infections. Both virus types were easily detected in all types of organs tested
      or EHV-2 in 79% cases and EHV-5 in 63%. In DNA from PBMC or buffy-coat EHV-2 was
      found in 20% cases and EHV-5 in 10%, all except one positive were foals. Co
      culture of PBMC on fetal horse kidney cells was efficient for detecting EHV-2 but
      not for EHV-5. We verify here for the first time infections with EHV-2 and 5 in
      horses in Iceland and show that both viruses are common.

PMID- 18336850
TI  - Spermatogenesis and chromatin condensation in male germ cells of sea cucumber
      Holothuria leucospilota (Clark, 1920).
AB  - Male germ cells in the testis of Holothuria leucospilota can be divided into 12
      stages based on ultrastructure and patterns of chromatin condensation. The
      spermatogonium (Sg) is a spherical-shaped cell with a diameter of about 6.5
      7microm. Its nucleus mostly contains euchromatin and small blocks of
      heterochromatin scattered throughout the nucleus. The nucleolus is prominent.
      Primary spermatocytes are divided into six stages, i.e., leptotene (LSc),
      zygotene (ZSc), pachytene (PSc), diplotene (DSc), diakinesis (DiSc) and metaphase
      (MSc). The early cells are round while in DiSc and in MSc cells are oval in
      shape. From LSc to MSc, the sizes of cells range from 3.5 to 4microm. LSc
      contains large blocks of heterochromatin as a result of increasingly condensed
      17nm fibers. In ZSc, the nucleus contains prominent synaptonemal complexes but a
      nucleolus is absent. In PSc, heterochromatin blocks are tightly packed together
      by 26nm fibers and appeared as large patches in DSc. Heterochromatin patches were
      enlarged to form chromosomes in DiSc and MSc and then the chromosome are moved to
      be aligned along equatorial region. The secondary spermatocyte (SSc) is an oval
      cell about 4.5-5.5microm. Their nuclei contain large clumps of heterochromatin
      along the nuclear envelope and in the center nuclear region. Spermatids are
      divided into two stages, i.e., early spermatid (ESt) and late spermatid (LSt).
      The nuclei decrease in size by a half and become spherical; thus the chromatin
      fibers condensed into 20nm and are closely packed together leaving only small
      spaces in LSt. The spermatozoa (Sz), with chromatin tightly packed in the
      spherical nucleus with a diameter of 2microm and a small acrosome situated at the
      anterior of the nucleus. The tail consists of a pair of centrioles lying
      perpendicular to each other and surrounded by a mitochondrial ring, and an
      axonemal complex, surrounded by a plasma membrane.

PMID- 18336851
TI  - Involvement of SREBPs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption
      of lipid metabolism in male guinea pig.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has multiple toxic effects causing a
      wasting syndrome characterized by a loss of body weight accompanied by a decrease
      in adipose tissue weight. To elucidate the mechanism behind this syndrome, we
      investigated the changes in lipid metabolism 7 and 21 days after a single
      intraperitoneal injection of TCDD at 1 microg/kg body weight to male guinea pigs.
      TCDD caused the symptoms of the syndrome, body weight loss with a decrease in
      adipose tissue weight, while it increased the levels of triacylglycerols, total
      cholesterols, and free fatty acids in plasma. On day 7, TCDD decreased the levels
      of CCAAT/enhancer binding protein (C/EBP) alpha, peroxisome proliferator
      activated receptor gamma, and glucose transporter 4, adipogenesis-related
      factors, in adipose tissue, whereas the levels of retinoid X receptor alpha,
      C/EBPbeta, C/EBPdelta, and c-Myc remained unchanged. TCDD also reduced the levels
      of both p125 precursor and p68 active forms of sterol regulatory element binding
      protein (SREBP)-1 and -2, the lipogenesis-related factors, and downregulated
      their DNA binding activity in adipose tissue, while it raised the levels of their
      p68 active forms and increased their DNA binding activity in the liver. TCDD
      decreased mRNA and protein levels of acetyl-CoA carboxylase and HMG-CoA synthase
      in the liver and adipose tissue. Similar results were obtained on day 21. These
      results suggest that TCDD disrupts lipid metabolism through changes in the
      expression levels of the adipogenesis-related and lipogenesis-related proteins in
      the liver and adipose tissue, and SREBPs would be involved in the development of
      the wasting syndrome.

PMID- 18336852
TI  - Tumor necrosis factor-alpha induces MMP-9 expression via p42/p44 MAPK, JNK, and
      nuclear factor-kappaB in A549 cells.
AB  - Matrix metalloproteinases (MMPs), in particular MMP-9, have been shown to be
      induced by cytokines including tumor necrosis factor-alpha (TNF-alpha) and
      contributes to airway inflammation. However, the mechanisms underlying MMP-9
      expression induced by TNF-alpha in human A549 cells remain unclear. Here, we
      showed that TNF-alpha induced production of MMP-9 protein and mRNA is determined
      by zymographic, Western blotting, RT-PCR and ELISA assay, which were attenuated
      by inhibitors of MEK1/2 (U0126), JNK (SP600125), and NF-kappaB (helenalin), and
      transfection with dominant negative mutants of ERK2 (DeltaERK) and JNK
      (DeltaJNK), and siRNAs for MEK1, p42 and JNK2. TNF-alpha-stimulated
      phosphorylation of p42/p44 MAPK and JNK were attenuated by pretreatment with the
      inhibitors U0126 and SP600125 or transfection with dominant negative mutants of
      DeltaERK and DeltaJNK. Furthermore, the involvement of NF-kappaB in TNF-alpha
      induced MMP-9 production was consistent with that TNF-alpha-stimulated
      degradation of IkappaB-alpha and translocation of NF-kappaB into the nucleus
      which were blocked by helenalin, but not by U0126 and SP600125, revealed by
      immunofluorescence staining. The regulation of MMP-9 gene transcription by MAPKs
      and NF-kappaB was further confirmed by gene luciferase activity assay. MMP-9
      promoter activity was enhanced by TNF-alpha in A549 cells transfected with wild
      type MMP-9-Luc, which was inhibited by helenalin, U0126, or SP600125. In
      contrast, TNF-alpha-stimulated MMP-9 luciferase activity was totally lost in
      cells transfected with mutant-NF-kappaB MMP-9-luc. Moreover, pretreatment with
      actinomycin D and cycloheximide attenuated TNF-alpha-induced MMP-9 expression.
      These results suggest that in A549 cells, phosphorylation of p42/p44 MAPK, JNK,
      and transactivation of NF-kappaB are essential for TNF-alpha-induced MMP-9 gene
      expression.

PMID- 18336853
TI  - Nitrophenols isolated from diesel exhaust particles regulate steroidogenic gene
      expression and steroid synthesis in the human H295R adrenocortical cell line.
AB  - Studies of nitrophenols isolated from diesel exhaust particles (DEPs), 3-methyl-4
      nitrophenol (PNMC) and 4-nitro-3-phenylphenol (PNMPP) have revealed that these
      chemicals possess estrogenic and anti-androgenic activity in vitro and in vivo
      and that PNMC accumulate in adrenal glands in vivo. However, the impacts of
      exposure to these compounds on adrenal endocrine disruption and steroidogenesis
      have not been investigated. To elucidate the non-receptor mediated effects of
      PNMC and PNMPP, we investigated the production of the steroid hormones
      progesterone, cortisol, testosterone, and estradiol-17beta and modulation of nine
      major enzyme genes involved in the synthesis of steroid hormones (CYP11A,
      CYP11B1, CYP17, CYP19, 17betaHSD1, 17betaHSD4, CYP21, 3betaHSD2, StAR) in human
      adrenal H295R cells supplied with cAMP. Exposure to 10(-7) to 10(-5) M PNMC and 1
      mM 8-Br-cAMP for 48 h decreased testosterone, cortisol, and estradiol-17beta
      levels and increased progesterone secretion. At 10(-5) M, PNMC with 1 mM 8-Br
      cAMP significantly stimulated expression of the 17betaHSD4 and significantly
      suppressed expression of 3betaHSD2. In comparison, 10(-7) to 2 x 10(-5) M PNMPP
      with 1 mM 8-Br-cAMP for 48 h decreased concentrations of estradiol-17beta,
      increased progesterone levels, but did not affect testosterone and cortisol
      secretion due to the significant suppression of CYP17 and the non-significant but
      obvious suppression of CYP19. Our results clarified steroidogenic enzymes as
      candidates responsible for the inhibition or stimulation for the production of
      steroid hormones in the steroidogenic pathway, thus providing the first
      experimental evidence for multiple mechanisms of disruption of endocrine pathways
      by these nitrophenols.

PMID- 18336854
TI  - Reactive oxygen species-dependent HSP90 protein cleavage participates in
      arsenical As(+3)- and MMA(+3)-induced apoptosis through inhibition of telomerase
      activity via JNK activation.
AB  - The effects of six arsenic compounds including As(+3), MMA(+3), DMA(+3), As(+5),
      MMA(+5), and DMA(+5) on the viability of NIH3T3 cells were examined. As(+3) and
      MMA(+3), but not the others, exhibited significant cytotoxic effects in NIH3T3
      cells through apoptosis induction. The apoptotic events such as DNA fragmentation
      and chromosome condensation induced by As(+3) and MMA(+3) were prevented by the
      addition of NAC and CAT, and induction of HO-1 gene expression in accordance with
      cleavage of the HSP90 protein, and suppression of telomerase activity were
      observed in NIH3T3 cells under As(+3) and MMA(+3) treatments. An increase in the
      intracellular peroxide level was examined in As(+3)- and MMA(+3)-treated NIH3T3
      cells, and As(+3)- and MMA(+3)-induced apoptotic events were blocked by NAC, CAT,
      and DPI addition. HSP90 inhibitors, GA and RD, significantly attenuated the
      telomerase activity in NIH3T3 cells with an enhancement of As(+3)- and MMA(+3)
      induced cytotoxicity. Suppression of JNKs significantly inhibited As(+3)- and
      MMA(+3)-induced apoptosis by blocking HSP90 protein cleavage and telomerase
      reduction in NIH3T3 cells. Furthermore, Hb, SnPP, and dexferosamine showed no
      effect against As(+3)- and MMA(+3)-induced apoptosis, and overexpression of HO-1
      protein or inhibition of HO-1 protein expression did not affect the apoptosis
      induced by As(+3) or MMA(+3). These data provide the first evidence to indicate
      that apoptosis induced by As(+3) and MMA(+3) is mediated by an ROS-dependent
      degradation of HSP90 protein and reduction of telomerase via JNK activation, and
      HO-1 induction might not be involved.

PMID- 18336855
TI  - Inhibition of cyclooxygenase-2 aggravates secretory phospholipase A2-mediated
      progression of acute liver injury.
AB  - Our previous study [Bhave, V. S., Donthamsetty, S., Latendresse, J. R.,
      Muskhelishvili, L., and Mehendale, H. M. 2008-this issue. Secretory phospholipase
      A(2) mediates progression of acute liver injury in the absence of sufficient COX
      2. Toxicol Appl Pharmacol] showed that in the absence of sufficient induction and
      co-presence of cyclooxygenase-2 (COX-2), secretory phospholipase A(2) (sPLA(2))
      appearing in the intercellular spaces for cleanup of post-necrotic debris seems
      to contribute to the progression of toxicant-initiated liver injury, possibly by
      hydrolysis of membrane phospholipids of hepatocytes in the perinecrotic areas. To
      further test our hypothesis on the protective role of COX-2, male Fisher-344 rats
      were administered a selective COX-2 inhibitor, NS-398, and then challenged with a
      moderately toxic dose of CCl(4). This led to a 5-fold increase in the
      susceptibility of the COX-2 inhibited rats to CCl(4) hepatotoxicity and
      mortality. The CCl(4) bioactivating enzyme CYP2E1 protein, CYP2E1 enzyme
      activity, and the (14)CCl(4)-derived radiolabel covalently bound to the liver
      proteins were unaffected by the COX-2 inhibitor suggesting that the increased
      hepatotoxic sensitivity of the COX-2 inhibited rats was not due to higher
      bioactivation of CCl(4). Further investigation showed that this increased
      mortality was due to higher plasma and hepatic sPLA(2) activities, inhibited
      PGE(2) production, and progression of liver injury as compared to the non
      intervened rats(.) In conclusion, inhibition of COX-2 mitigates the tissue
      protective mechanisms associated with COX-2 induction, which promotes sPLA(2)
      mediated progression of liver injury in an acute liver toxicity model. Because
      increased sPLA(2) activity in the intercellular space is associated with
      increased progression of injury, and induced COX-2 is associated with
      hepatoprotection, ratios of hepatic COX-2 and sPLA(2) activities may turn out to
      be a useful tool in predicting the extent of hepatotoxicities.

PMID- 18336856
TI  - The risk of arsenic induced skin lesions in Bangladeshi men and women is affected
      by arsenic metabolism and the age at first exposure.
AB  - It is known that a high fraction of methylarsonate (MA) in urine is a risk
      modifying factor for several arsenic induced health effects, including skin
      lesions, and that men are more susceptible for developing skin lesions than
      women. Thus, we aimed at elucidating the interaction between gender and arsenic
      metabolism for the risk of developing skin lesions. This study is part of a
      population-based case-referent study concerning the risk for skin lesions in
      relation to arsenic exposure via drinking water carried out in Matlab, a rural
      area 53 km south-east of Dhaka, Bangladesh. We randomly selected 526 from 1579
      referents and all 504 cases for analysis of arsenic metabolites in urine using
      HPLC coupled to inductively coupled plasma mass spectrometry (HPLC-HG-ICPMS). The
      present study confirm previous studies, with the risk for skin lesions being
      almost three times higher in the highest tertile of %MA (adjusted OR 2.8, 95% CI:
      1.9-4.2, p < 0.001) compared to the lowest tertile. The present study is the
      first to show that the well documented higher risk for men to develop arsenic
      related skin lesions compared to women is mainly explained by the less efficient
      methylation of arsenic, as defined by a higher fraction of MA and lower fraction
      of DMA in the urine, among men. Our previously documented lower risk for skin
      lesions in individuals exposed since infancy, or before, was found to be
      independent of the observed arsenic methylation efficiency. Thus, it can be
      speculated that this is due to a programming effect of arsenic in utero.

PMID- 18336857
TI  - Conservation of fiber structure and CD46 usage by subgroup B2 adenoviruses.
AB  - Most subgroup B2 adenoviruses use CD46 as their primary receptor. Recent
      structural and mutagenesis studies suggested that Ad11 and Ad35 likely engage
      this receptor in a very similar fashion. However, no comparative studies
      assessing the cell-associated CD46 binding efficiencies of different Ad fibers
      have been performed. We solved the crystal structure of Ad35 fiber knob and
      constructed a model of the fiber knob complexed with CD46. Comparison of our
      model with that of Ad11-CD46 showed that despite a larger CD46-interacting region
      in the IJ loop of Ad11, the buried surface area was very similar, suggesting that
      both fiber knobs might exhibit similar binding. In support of this, cell based
      competition studies demonstrated almost identical binding efficiencies of Ad11
      and Ad35 fibers to cell surface CD46. These findings shed further light on CD46
      association by Ad and could impact the selection of novel Ad types for gene
      transfer.

PMID- 18336858
TI  - A new approximate solution for chlorine concentration decay in pipes.
AB  - Biswas et al. (1993. A model for chlorine concentration decay in pipes. Water
      Res. 27(12), 1715-1724) presented an analytical solution of a two-dimensional (2
      D) steady-state chlorine transport equation in a pipe under the turbulent
      condition and employed fractional error function and regression technique to
      develop an approximate solution. However, their approximate solution may not give
      a good result if the wall decay parameter is large. This paper provides a more
      accurate approximate solution of the 2-D steady-state chlorine transport equation
      under the turbulent condition. This new approximate solution has advantages of
      easy evaluation and good accuracy when compared with the approximate solution
      given by Biswas et al. (1993). In addition, this paper also develops a
      methodology that combines simulated annealing (SA) with this new approximate
      solution to determine the wall decay parameter. Two cases are chosen to
      demonstrate the application of the present approximate solution and methodology.
      The first case is to use this new approximate solution in simulating chlorine
      decay in pipes with the experiment-observed data given by Rossman (2006. The
      effect of advanced treatment on chlorine decay in metallic pipes. Water Res.
      40(13), 2493-2502), while the second case presents the determination of the wall
      consumption at the end of the pipe network.

PMID- 18336859
TI  - Photocatalytic oxidation of aqueous ammonia in model gray waters.
AB  - This study investigated the TiO2 photocatalytic degradation of aqueous ammonia
      (NH4+/NH3) in the presence of surfactants and monosaccharides at pH approximately
      10.1. Initial rates of NH4+/NH3 photocatalytic degradation decreased by
      approximately 50-90% in the presence of anionic, cationic, and nonionic
      surfactants and monosaccharides. Through correlation analysis, we concluded that
      scavenging of hydroxyl radical (.OH) by the products of surfactant/monosaccharide
      photocatalytic degradation, including carbonate and formate, could explain
      approximately 80% of the variance in initial rates of NH4+/NH3 removal in our
      system. Addition of a supplemental .OH source (H2O2) enhanced the rate of
      NH4+/NH3 degradation in the presence of the surfactant Brij 23 lauryl ether (Brij
      35), further supporting the idea that .OH scavenging is the mechanism by which
      surfactants and monosaccharides decreased initial rates of NH4+/NH3
      photocatalytic degradation. Despite slowed rates of NH4+/NH3 degradation, both
      surfactants/monosaccharides and NH4+/NH3 were removed by TiO2 photocatalysis,
      indicating that this process can effectively remove both carbonaceous and
      nitrogenous biochemical oxygen demand from gray water.

PMID- 18336860
TI  - Dynamics and dynamic modelling of H2S production in sewer systems.
AB  - Accurate and reliable predictions of sulfide production in a sewer system greatly
      benefit formulation of appropriate strategies for optimal sewer management. Sewer
      systems, rising main systems in particular, are highly dynamic in terms of both
      flow and wastewater composition. In order to get an insight in sulfide production
      as a response to the dynamic changes in sewer conditions, several measurement
      campaigns were conducted in two rising mains in Gold Coast, Australia. The levels
      of various sulfur species and volatile fatty acids (VFAs) were monitored through
      hourly sampling for periods ranging from 8 to 29 h. The results of these field
      studies showed large temporal as well as spatial variations in sulfide
      generation. A dynamic sewer model taking into account the hydraulics and the
      biochemical transformation processes was formulated and calibrated and validated
      using the data collected during the four measurement campaigns at the two sites.
      The model was demonstrated to reasonably well describe the temporal and spatial
      variations in sulfide, sulfate and VFA concentrations. Application of the model
      was illustrated with a case study aimed to optimize oxygen injection to one of
      the two mains studied, which is being used as a means to control sulfide
      production on this site. The model predicted that, moving the current oxygen
      injection point to a location close to the end of the sewer line could achieve
      the same degree of sulfide control with only 50% of the current oxygen use. This
      study highlighted that the location at which oxygen is injected plays a major
      role in sulfide control and a dynamic model could be used to make a proper choice
      of the location.

PMID- 18336861
TI  - Whole-stream phosphorus cycling: testing methods to assess the effect of
      saturation of sorption capacity on nutrient uptake length measurements.
AB  - The cycling rate of nutrients such as phosphorus (P) is a fundamental parameter
      in stream ecology. In whole-stream ecosystem experiments, cycling rates are often
      assessed using continuous short-term nutrient addition studies. While several
      simplifying assumptions are generally recognised, these are rarely, if ever,
      fully tested under field conditions. One principal assumption is that uptake
      (sorption) processes do not become saturated during periods of nutrient addition,
      which is perhaps questionable from laboratory studies of soluble reactive
      phosphorus (SRP) sorption kinetics. Three approaches were developed and tested,
      which bridged the gap between laboratory-based net (sum of uptake and release)
      sorption kinetics and whole-stream assessments of P uptake. These were applied to
      a short-term (three times mean travel time of water in the studied reach) whole
      stream multiple-rate P addition. The results were then tested independently with
      a whole-stream long-term (15 times mean travel time) SRP addition. The net
      sorption kinetics were not altered during the short-term addition with low SRP
      additions, 9-16 microg L(-1) (two to three times the ambient concentration).
      Although this may not be the case at higher added concentrations (as possibly
      hinted at five times the ambient concentration), the long-term addition showed no
      change in P uptake length with a P addition (39 microg L(-1)) 16 times higher
      than the ambient concentration.

PMID- 18336862
TI  - Assessment of the effects of soil PAH accumulation by a battery of
      ecotoxicological tests.
AB  - Surface soils were collected at remote, urban and industrial sites in the
      Southern of Italy in order to evaluate PAH concentrations and assess the toxic
      effects by a battery of ecotoxicological tests. The tests were performed on whole
      soils and on both organic and aqueous extracts. Further goal of this study was to
      integrate the results coming from each test and matrix in a synthetic toxicity
      index. The highest summation sigmaPAH concentrations were measured at the
      industrial soil, although this one did not show an high ecotoxicological risk.
      Among the performed tests, the phytotoxicity tests showed the highest
      sensitivity. For whole soil, the worst case always has been represented by test
      through bacteria. Our results could represent the first step toward the selection
      of a proper battery to characterize the soil ecotoxicological risk.

PMID- 18336863
TI  - Removal of humic acid using TiO2 photocatalytic process--fractionation and
      molecular weight characterisation studies.
AB  - The photocatalytic removal of humic acid (HA) using TiO2 under UVA irradiation
      was examined by monitoring changes in the UV(254) absorbance, dissolved organic
      carbon (DOC) concentration, apparent molecular weight distribution, and
      trihalomethane formation potentials (THMFPs) over treatment time. A resin
      fractionation technique in which the samples were fractionated into four
      components: very hydrophobic acids (VHA), slightly hydrophobic acids, hydrophilic
      charged (CHA) and hydrophilic neutral (NEU) was also employed to elucidate the
      changes in the chemical nature of the HA components during treatment. The
      UVA/TiO2 process was found to be effective in removing more than 80% DOC and 90%
      UV(254) absorbance. The THMFPs of samples were decreased to below 20 microg l(-1)
      after treatments, which demonstrate the potential to meet increasingly stringent
      regulatory level of trihalomethanes in water. Resin fractionation analysis showed
      that the VHA fraction was decreased considerably as a result of photocatalytic
      treatments, forming CHA intermediates which were further degraded with increased
      irradiation time. The NEU fraction, which comprised of non-UV-absorbing low
      molecular weight compounds, was found to be the most persistent component.

PMID- 18336864
TI  - The use of physiological characteristics for comparison of organic compounds
      phytotoxicity.
AB  - The influence of intact (FLT) and photomodified (phFLT) fluoranthene (0.05, 0.5
      and 5 micromol l(-1)) and herbicide Basagran (5, 20, 35 and 50 nmol l(-1)) on the
      germination, growth of seedlings and photosynthetic processes in pea plants
      (Pisum sativum L., cv. Garde) was investigated. The germination was significantly
      inhibited already by the lowest concentration (0.05 micromol l(-1)) of FLT and
      phFLT, while Basagran caused inhibition only in higher concentrations (35 and 50
      nmol l(-1)). The growth of roots was significantly inhibited by higher
      concentration 5 micromol l(-1) of both FLT and phFLT and the shoot of seedlings
      was significantly influenced only by photomodified form. The length of root and
      shoot was inhibited already by concentration 5 nmol l(-1) of Basagran. Organic
      compounds applied on chloroplasts suspension influenced primary photochemical
      processes of photosynthesis. In chlorophyll fluorescence parameters, the
      significant increase of F(0) values and the decrease of F(V)/F(M) and Phi(II)
      values by application of FLT (0.5 and 5 micromol l(-1)) and phFLT (0.05, 0.5 and
      5 micromol l(-1)) was recorded. The maximum capacity of PSII (F(V)/F(M)) was
      influenced by the highest (50 nmol l(-1)) and the effective quantum yield of PSII
      (Phi(II)) already by the lowest (5 nmol l(-1)) concentration of Basagran. Hill
      reaction activity decreased and was significantly inhibited by higher
      concentration (0.5 and 5 micromol l(-1)) of FLT and phFLT and already by the
      lowest concentration (5 nmol l(-1)) of Basagran.

PMID- 18336865
TI  - Diffusion of PAH and PCB from contaminated sediments with and without mineral
      capping; measurement and modelling.
AB  - A novel laboratory microcosm test was developed to measure the diffusion of
      native PAHs and PCBs from sediments in the presence and absence of a capping
      layer. Diffusive flux of 15 PAHs and 7 PCBs from uncapped sediment from Oslo
      harbour was 3.8+/-0.9 microg m(-2)d(-1) and 0.010+/-0.003 microg m(-2)d(-1),
      respectively. The flux from sediments capped with 1cm mineral cap (crushed
      limestone or crushed gneiss (0-2mm)), observed during the first 410 d, was 3.5
      7.3% of the flux from uncapped sediments. By measuring freely dissolved pore
      water concentrations of 10 PAHs the flux in the microcosm was modelled with
      steady state and transient diffusion models. The measured flux from uncapped
      sediment was 27-290% of modelled steady state flux. Good agreement was also found
      between the measured flux of pyrene from capped sediment and the flux modelled
      with the transient model when fitting only with the distribution coefficients for
      pyrene between the cap material and water (Kd_pyr). Fitted Kd_pyr, (210 and 23 l
      kg(-1) for limestone and gneiss, respectively) was in the same order of magnitude
      as K(d) calculated from organic carbon content in the cap materials (68 and 14 l
      kg(-1) respectively). Calculation of the efficiency of a hypothetical cap with 10
      cm diffusion path shows that the increased diffusion path length alone can yield
      a flux reduction >99% through a strong increase in the stagnant diffusive
      boundary layer from <1 to 100mm.

PMID- 18336866
TI  - Electrochemical determination of anaerobic microbial decay coefficients.
AB  - The biokinetics of attached and suspended bacteria are an essential component of
      activated sludge models, anaerobic digestion models and biofilm models. These
      parameters are often assumed or "confirmed" based on the goodness-of-fit of the
      bioprocess models. Using a microbial fuel cell with a baffled reactor chamber,
      the attached- and mixed-growth microbial decay coefficients were evaluated under
      anaerobic conditions. The capability for real-time voltage recording allows easy
      and accurate measurement of the anaerobic microbial decay coefficients (b(L),
      lysis-regrowth approach), which were determined to be 0.11+/-0.01 and 0.15+/-0.01
      d(-1) for attached (to anode) and mixed (present in the anode chamber) growth
      microorganisms, respectively. The corresponding half-saturation constants using
      glucose as a substrate were 204+/-10 and 123+/-1 mg COD l(-1). Hence, like an
      oxygen uptake rate-based approach to measure the microbial kinetics under aerobic
      conditions, the electrochemical recording provides an attractive method to
      measure anaerobic microbial decay coefficients.

PMID- 18336867
TI  - Clinical implications of the basic defects in Cockayne syndrome and xeroderma
      pigmentosum and the DNA lesions responsible for cancer, neurodegeneration and
      aging.
AB  - Cancer, aging, and neurodegeneration are all associated with DNA damage and
      repair in complex fashions. Aging appears to be a cell and tissue-wide process
      linked to the insulin-dependent pathway in several DNA repair deficient
      disorders, especially in mice. Cancer and neurodegeneration appear to have
      complementary relationships to DNA damage and repair. Cancer arises from
      surviving cells, or even stem cells, that have down-regulated many pathways,
      including apoptosis, that regulate genomic stability in a multi-step process.
      Neurodegeneration however occurs in nondividing neurons in which the persistence
      of apoptosis in response to reactive oxygen species is, itself, pathological.
      Questions that remain open concern: sources and chemical nature of naturally
      occurring DNA damaging agents, especially whether mitochondria are the true
      source; the target tissues for DNA damage and repair; do the human DNA repair
      deficient diseases delineate specific pathways of DNA damage relevant to clinical
      outcomes; if naturally occurring reactive oxygen species are pathological in
      human repair deficient disease, would anti-oxidants or anti-apoptotic agents be
      feasible therapeutic agent?

PMID- 18336868
TI  - The influence of water quality on the embryonic survivorship of the Oregon
      spotted frog (Rana pretiosa) in British Columbia, Canada.
AB  - In Canada, the Oregon spotted frog (Rana pretiosa) is a critically endangered
      species with only three known populations and an estimated breeding population of
      less than 400 located in isolated sites in the extreme south-west corner of
      British Columbia. Floating Nitex cages were used to assess embryonic survivorship
      in two populations of Oregon spotted frogs from 2002-2005. One population, near
      Aldergrove, BC experienced declines in population size while the other
      population, at Maria Slough, increased during the period 1997-2001. During embryo
      development, we measured trace metals, nutrients and physical parameters in the
      water at each site. These were used to test the hypothesis that water quality
      parameters were correlated with embryonic survivorship. During the study period
      in the declining population at Aldergrove R. pretiosa bred at two distinct sub
      sites (A and B) located 500 m apart within the wetland. Mean embryonic
      survivorship varied from 9% to 36% at sub site A and from 78% to 88% at sub site
      B whereas in the population in Maria Slough, the mean embryonic survivorship
      varied from 77% to 84%. Sulphate was the only water chemistry variable that
      differed significantly between the two study sites and was the highest at Maria
      Slough. A weak significant positive correlation was found between chloride and
      embryonic survivorship and conductivity and embryonic survivorship. A multiple
      regression model found conductivity was the only significant variable. We
      concluded that natural water chemistry conditions of low chloride and
      consequently low conductivity may be contributing to low embryonic survivorship
      in the population of R. pretiosa at MD Aldergrove, BC.

PMID- 18336869
TI  - Carotid intima-media thickness predicts the development of cardiovascular events
      in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To establish whether carotid intima-media wall thickness (IMT) may be
      a good predictor for the development of cardiovascular (CV) events in patients
      with rheumatoid arthritis (RA). METHODS: A series of 47 RA patients who at the
      time of recruitment did not have traditional CV risk factors or CV disease were
      assessed by carotid ultrasonography. Carotid IMT and carotid plaques were
      measured in the right common carotid artery. Then, a prospective assessment of
      the CV outcome was performed over a 5-year period. Logistic regression models and
      receiver operating characteristic curves were performed to evaluate the ability
      of different variables to predict CV events. RESULTS: Carotid IMT was greater in
      RA patients who over the extended follow-up experienced CV events (1.01 +/- 0.16
      mm) compared with the remaining RA patients who did not have CV complications
      (0.74 +/- 0.12 mm) (P < 0.001). Also, carotid IMT categorized in quartiles was
      strongly associated with CV events. In this regard, none of the patients with
      carotid IMT less than 0.77 mm had CV events. However, 6 of the 10 patients with
      carotid IMT greater than 0.91 mm experienced CV events (P value for the trend
      <0.001). Carotid IMT yielded a high predictive power for the development of CV
      events over the 5-year follow-up period. The area under the receiver operating
      characteristic curve was 0.93 for a model that only included carotid IMT and 0.90
      for carotid plaque. CONCLUSIONS: The results from the present study support the
      use of carotid ultrasonography as a predictor of CV events in RA.

PMID- 18336870
TI  - High prevalence of hypovitaminosis D in Morocco: relationship to lifestyle,
      physical performance, bone markers, and bone mineral density.
AB  - OBJECTIVES: We undertook this study to determine the prevalence of
      hypovitaminosis D, its determinants, and its relationships to physical
      performance, serum parathyroid hormone (PTH) concentration, bone mineral density,
      and biochemical markers of bone turnover in healthy, ambulatory, pre- and
      postmenopausal women. METHODS: The group studied included 415 women aged 24 to 77
      years. Between July and September, we assessed calcium intake and measured serum
      calcium, phosphorus, albumin, alkaline phosphate, 25-hydroxyvitamin D (25(OH)D),
      PTH, osteocalcin, and C-terminal cross-linking telopeptide of Type I collagen. We
      also measured bone mineral density (BMD) by dual-energy radiograph absorptiometry
      in the spine and total femur. Three tests were used to assess physical
      performance: timed get-up-and-go test, 5-times-sit-to-stand test, and 2.4 m speed
      walk. RESULTS: The prevalence of vitamin D insufficiency (<30 ng/mL) was 91%. In
      multiple logistic regression, the main determinants of hypovitaminosis D were age
      >55 years (OR 2.14 [95% IC, 1.1-4.1; P = 0.026)], wearing a veil [OR 2 (95% IC,
      1.1-4; P = 0.04)], time spent outdoors less than 30 min/d [OR 2.8 (95% IC: 1.4
      5.7; P = 0.003)], and daily calcium intake less than 700 mg [OR 2.39 (95% IC, 1.2
      4.7; P < 0.01)]. A significant inverse correlation between 25 OH and osteocalcin
      (r = -0,18, P < 0001), 25 OH, and Type I collagen (r = -0,15, P = 0003) were
      observed. By Locally Weighted Regression and Scatterplot Smoothing technique,
      there was an increase in PTH level when S-25(OH)D was below 30 ng/mL. After
      adjustment for age, both spine BMD and total femoral BMD failed to show any
      significant correlation with serum 25(OH)D and PTH. There was no correlation
      between any physical performance tests and 25(OH)D levels. CONCLUSIONS: Our study
      showed that during the summer season, vitamin D insufficiency is very common in
      healthy adult Moroccan women. Lack of sun exposure and veiled clothing style were
      the most important factors that influenced hypovitaminosis D. Patients with
      hypovitaminosis D had a high bone turnover, whereas there was no effect on BMD
      and physical performance. Further research is needed to evaluate the clinical
      impact of the above findings.

PMID- 18336871
TI  - Role of interleukin-6 in the anemia of chronic disease.
AB  - OBJECTIVES: To review evidence supporting the involvement of interleukin-6 in the
      pathophysiology of anemia of chronic disease, to discuss the possible molecular
      mechanisms driving this condition in patients with end-stage renal disease and
      rheumatoid arthritis, and to review clinical manifestations in these patients.
      METHODS: A literature search was performed using MEDLINE and the reference lists
      of relevant review articles. The following key words were used in the MEDLINE
      search: interleukin-6, "anemia of chronic disease" OR "anemia of inflammation,"
      "pathophysiology," "end-stage renal disease," and "rheumatoid arthritis." The
      search was limited to English-language articles. RESULTS: Interleukin-6 is a
      multifunctional cytokine that regulates the hepatic acute-phase response, the
      immune response, inflammation, and hematopoiesis. Interleukin-6 appears to be the
      central mediator of anemia of chronic disease in a range of inflammatory
      diseases, including end-stage renal disease and rheumatoid arthritis, through
      increased generation of hepcidin and the resultant alterations in iron
      metabolism. Clinically, patients with anemia of chronic disease are more likely
      to experience increased disease severity and duration than patients who have
      chronic disease without anemia. CONCLUSIONS: The integral role of interleukin-6
      in the pathogenesis of anemia of chronic disease suggests that it could be an
      important therapeutic target. Currently available treatments target interleukin
      1, and tumor necrosis factor-alpha and its receptors, and have been only
      partially successful. Given the complexity of the cytokine pathways that are
      involved in the pathogenesis of inflammatory disease, further studies are
      required to test other molecular targets.

PMID- 18336872
TI  - Multimorbidity: prevalence, effect on quality of life and daily functioning, and
      variation of this effect when one condition is a rheumatic disease.
AB  - OBJECTIVES: To examine the prevalence and effect of multimorbidity on health
      related quality of life (HRQoL) and daily functioning in the general population,
      and to analyze the influence on HRQoL and daily functioning of multimorbidity
      including a rheumatic disease. METHODS: A national health survey was conducted on
      2192 randomly selected adults in Spain. Multimorbidity was defined as the co
      occurrence of at least 2 chronic diseases, as defined by self-report. All
      subjects completed the 12-item short form (SF-12) health survey and the Health
      Assessment Questionnaire (HAQ). Estimates and 95% confidence intervals (CI) of
      the prevalence of multimorbidity were obtained. The effect on HAQ and SF-12
      scores is presented as beta-coefficients obtained from multiple linear
      regressions. RESULTS: The estimated prevalence of multimorbidity was 30% (95% CI
      25 to 34), and the prevalence of multimorbidity including a rheumatic disease was
      17% (95% CI 13 to 20). Multimorbidity was associated with impaired daily
      functioning [HAQ beta = 0.07 (95% CI 0.02 to 0.11)], and lower HRQoL [SF
      12(physical component) beta = -4.2 (95% CI -5.2 to -3.22); SF-12(mental
      dimension) beta = -3.3 (95% CI -4.5 to -2.2)]. Subjects with multimorbidity
      including a rheumatic disease reported worse scores than those without a
      rheumatic disease: HAQ beta 0.13 (95% CI 0.07 to 0.18) versus -0.03 (95% CI -0.08
      to 0.02), and SF-12(physical component) beta -6.5 (95% CI -5.2 to -3.2) versus
      0.5 (95% CI -0.7 to 1.7). CONCLUSIONS: Multimorbidity is frequent in the general
      population and can considerably impair daily functioning and HRQoL. Having a
      rheumatic disease worsens these outcomes.

PMID- 18336873
TI  - Bone marrow edema in the cervical spine of symptomatic rheumatoid arthritis
      patients.
AB  - OBJECTIVE: To investigate the frequency and clinical significance of bone marrow
      edema (BME) in a series of patients with rheumatoid arthritis (RA) and
      symptomatic involvement of the cervical spine. METHODS: We studied 19 consecutive
      RA patients with cervical spine magnetic resonance imaging (MRI) according to a
      specifically designed protocol that included short inversion time inversion
      recovery sequences. All cases had neck pain unresponsive to conventional
      treatment, neurological symptoms, or signs suggestive of cervical myelopathy, or
      cervical pain with evidence of atlantoaxial subluxation on radiographs. RESULTS:
      The mean age of the 19 patients (15 women and 4 men) at time of the study was 59
      +/- 12 years (range, 23-82) and the median disease duration was 14 +/- 7.4 years
      (range, 4-30). BME was observed in 74% (14/19) of the patients: at the
      atlantoaxial level alone in 16% of the patients; subaxially alone in 16%; and at
      both levels in 42% of the patients. At the atlantoaxial level, BME was usually
      observed involving the odontoid process, whereas subaxially BME was limited to
      the vertebral plates and the interapophyseal joints. Patients with BME had higher
      erythrocyte sedimentation rate (ESR) values at the time of MRI examination (P =
      0.014) and more severe atlantoaxial joint MRI synovitis scores (P = 0.05)
      compared with the remaining patients; the frequency of odontoid erosions was also
      greater in this group, but the difference did not reach statistical significance.
      Altogether, these data suggest a more severe inflammatory response in these
      patients. In this group a significant correlation was found between BME scores at
      atlantoaxial level and (1) ESR values (r = 0.854; P = 0.001) and (2) atlantoaxial
      joint MRI synovitis scores (r = 0.691; P = 0.001). CONCLUSION: BME is frequently
      observed in patients with established RA and symptomatic cervical spine
      involvement. Both atlantoaxial and subaxial levels are equally affected. The
      presence of BME seems related to the intensity of the inflammatory response and
      to the severity of the atlantoaxial joint synovitis.

PMID- 18336874
TI  - Safety of biologic therapy in rheumatoid arthritis and other autoimmune diseases:
      focus on rituximab.
AB  - OBJECTIVES: To review the safety of biologic agents used to treat rheumatoid
      arthritis (RA) and other autoimmune diseases, with a focus on rituximab. METHODS:
      Information was gathered from a search of the PubMed database and from major
      congress abstract listings through June 2007. RESULTS: Rituximab is approved for
      treating RA in patients with an inadequate response to TNF inhibitors and is
      under study in other indications for RA and other autoimmune disorders. The
      current safety profile of rituximab in RA is known from Phase II and III studies
      conducted preapproval, treating approximately 750 patients, as well as from long
      term extension studies with repeated therapy. Clinical trials have established
      that the most common adverse events are infusion-associated reactions, seen in 29
      to 40% of patients, most of which are mild to moderate and occur following the
      first rituximab infusion, with incidence and severity decreasing with subsequent
      infusions. Rates of infections and serious infections to date are within the
      range expected for RA patients treated with other biologic agents, but the longer
      term effects of B-cell depletion and the effects of repeated treatment on the
      risk of infections are uncertain. Information is limited for rituximab safety in
      other autoimmune disorders but current data do not suggest that there is a
      significant difference in adverse events from that previously reported.
      CONCLUSIONS: Rituximab is an important addition to the rheumatologist's
      armamentarium for the treatment of difficult RA and ongoing trials will determine
      its utility in other indications for RA and other autoimmune conditions. The true
      safety profile of rituximab will emerge as larger numbers of patients are treated
      in routine clinical practice.

PMID- 18336875
TI  - Medication adherence of patients with selected rheumatic conditions: a systematic
      review of the literature.
AB  - OBJECTIVE: Nonadherence with medication treatment has been found to occur in
      large proportions of patients with a broad range of chronic conditions. Our aim
      was to perform a systematic review of the literature examining adherence with
      treatments for inflammatory rheumatic conditions to assess the magnitude of the
      problem in this patient population. METHODS: A MEDLINE search of English language
      literature was performed to identify studies published between January 1, 1985
      and November 30, 2007 that evaluated adherence with chronic medications needed in
      the treatment of rheumatic conditions. RESULTS: A total of 20 articles met the
      criteria for evaluation, the majority of which focused on the treatment of
      rheumatoid arthritis. Most of the studies examined the use of nonsteroidal anti
      inflammatory medications and disease-modifying antirheumatic drugs. Adherence was
      assessed based on self-report, pill counts, pharmacy dispensings, openings of
      pill containers using electronic devices, laboratory assays, and physician
      assessment. Adherence varied greatly based on the adherence measure used,
      arthritic condition evaluated, and medication under study. Overall, the highest
      rates of adherence were based on self-reports for a wide variety of medications
      and conditions (range of persons reporting adherence was 30 to 99%), while the
      lowest adherence rates were for allopurinol based on pharmacy dispensings (18
      26%). CONCLUSIONS: Adherence has not been widely examined for most chronic
      inflammatory rheumatic conditions and the few studies that exist used different
      definitions and populations, thus limiting any conclusions. However, the current
      literature does suggest that nonadherence is a substantial problem.

PMID- 18336876
TI  - Primary renal synovial sarcoma.
AB  - Synovial sarcoma of the kidney is a recently reported neoplasm. Only 33 cases
      have been reported in published studies. It is a difficult neoplasm to
      differentiate from other renal masses and requires specific molecular/genetic
      testing. Currently, no treatment guidelines have been established. Accurate
      diagnosis is imperative to implement effective therapy.

PMID- 18336877
TI  - Delivery of intercellular adhesion molecule-1 antisense oligonucleotides using a
      topical hydrogel tissue sealant in a murine partial nephrectomy/ischemia model.
AB  - OBJECTIVES: Ischemia/reperfusion injury is a leading cause of renal damage which
      can be improved with antisense oligonucleotide gene therapy. We have shown that
      polyethylene glycol (PEG) hydrogel, which also functions as a tissue sealant, is
      an effective topical delivery vehicle for oligonucleotides in a murine partial
      nephrectomy model. The objective of this study was to use and evaluate this
      method against intercellular adhesion molecule-1 (ICAM-1) to prevent tissue
      damage. METHODS: Sixty mice underwent left upper pole partial nephrectomy with 45
      minutes of warm ischemia, randomized to treatment with 50 microg ICAM-1 antisense
      oligonucleotides embedded in PEG hydrogel, no therapy, or sham surgery. Kidneys
      were harvested at 24 hours and 3, 4, and 5 days. The specimens were evaluated by
      quantitative real-time polymerase chain reaction (qRT-PCR) for ICAM-1 messenger
      ribonucleic acid (mRNA), immunohistochemical staining for ICAM-1 protein, and
      standard histology. RESULTS: At 24 hours, qRT-PCR and immunohistochemistry data
      showed a significant reduction in ICAM-1 mRNA and protein expression in the
      antisense group versus the ischemia group, but no difference at 3 to 5 days.
      Histologically there was reduced inflammation and necrosis in the cortex at 24
      hours. The outer and inner medulla also showed improvement at 3 to 5 days in the
      antisense group as opposed to the ischemia group. CONCLUSIONS: Topical PEG
      hydrogel delivery of antisense ICAM-1 oligonucleotides demonstrated decreased
      ICAM-1 mRNA expression, reduced ICAM-1 protein staining, and decreased cellular
      damage. The application of gene therapy through this novel topical delivery
      system holds potential for a highly specific, localized method of preventing
      tissue damage after ischemia/reperfusion injury.

PMID- 18336878
TI  - Serum creatinine predicts success in retrograde ureteral stent placement in
      patients with pelvic malignancies.
AB  - OBJECTIVES: To evaluate serum hemoglobin, baseline serum creatinine, serum
      creatinine at the diagnosis of obstructive hydronephrosis, and the increase in
      serum creatinine greater than baseline to predict for success in retrograde
      ureteral stent placement in patients with pelvic malignancies. METHODS: In a
      retrospective chart review, we identified 57 patients at our institution with
      obstructive hydronephrosis secondary to pelvic malignancies in which retrograde
      ureteral stent placement was attempted from January 2002 to May 2005. The patient
      charts were reviewed for the baseline serum creatinine, preoperative serum
      creatinine and hemoglobin, and serum creatinine at presentation of obstructive
      hydronephrosis. This population was divided into group 1 (n = 31, 54%), in which
      retrograde stent placement was successful, and group 2 (n = 26, 46%), in which
      stent placement failed and subsequent percutaneous nephrostomy tube placement was
      required. The Student t test was used to determine whether a significant
      difference existed between the two groups for each laboratory parameter. RESULTS:
      The serum hemoglobin and baseline creatinine were not significantly different
      between the two groups and could not be used to predict for the success or
      failure of stent placement (P = 0.10 and P = 0.59, respectively). However, the
      average serum creatinine at presentation of obstructive hydronephrosis was
      significantly different between group 1 (2.4 +/- 1.4 ng/dL) and group 2 (5.3 +/-
      6.3; P = 0.014), as was an increase in serum creatinine greater than baseline (P
      = 0.002). CONCLUSIONS: The results of this study have shown that the serum
      creatinine level at the presentation of obstructive hydronephrosis can be used to
      predict for success in retrograde ureteral stent placement in patients with
      pelvic malignancies.

PMID- 18336879
TI  - Laparoscopic adrenalectomy for adrenal masses: does size matter?
AB  - OBJECTIVES: To examine the impact of adrenal tumor size on perioperative
      morbidity and postoperative outcomes in patients undergoing laparoscopic
      adrenalectomy. METHODS: A total of 227 laparoscopic adrenalectomies were divided
      in three groups according to size as estimated by pathologic specimen maximum
      diameter: less than 6 cm (group 1, n = 140), between 6 and 7.9 cm (group 2, n =
      47), and equal to or larger than 8 cm (group 3, n = 40). We prospectively
      recorded and analyzed clinical and pathologic data. RESULTS: Average operative
      time was 60 minutes (range, 50 to 90 minutes) for group 1, 75 minutes (range, 65
      to 105 minutes) for group 2, and 80 minutes (range, 65 to 120 minutes) for group
      3. Estimated blood loss, median (interquartile range) was 50 mL (range, 20 to 100
      mL), 100 mL (range, 48 to 225 mL), and 100 mL (range, 50 to 475 mL) for groups 1,
      2, and 3, respectively. We observed a total of 10, 4, and 4 complications in
      groups 1, 2, and 3, respectively. Average hospital stay was 2 days (range, 2 to 3
      days), 2 days (range, 2 to 3 days), and 3 days (range, 2 to 4 days),
      respectively, for groups 1, 2, and 3. Operative time, average blood loss, and
      mean hospital stay were significantly higher (P <or=0.05) for group 3 compared
      with group 1. CONCLUSIONS: Laparoscopic adrenalectomy in large adrenal masses (8
      cm or greater) is associated with significantly longer operative time, increased
      blood loss, and longer hospital stay, without affecting perioperative morbidity.

PMID- 18336880
TI  - Effect of menthol on detrusor smooth-muscle contraction and the micturition
      reflex in rats.
AB  - OBJECTIVES: To investigate the effects of menthol, an activator of the
      temperature-sensitive transient receptor potential family member TRPM8, on
      detrusor smooth-muscle contraction and the micturition reflex in rats. METHODS:
      We evaluated the effect of intravesical infusion of 1 or 3 mM menthol by
      cystometry in conscious female Sprague-Dawley rats. Some of the animals were
      pretreated with 125 mg/kg capsaicin subcutaneously 4 days earlier. The parameters
      measured were voided volume (VV), residual volume (RV), volume threshold for
      inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP),
      and pressure threshold for inducing micturition (PT). Strips of detrusor muscle
      were mounted in organ baths to study the effect of menthol on the contractile
      response to 0.01 mM carbachol. RESULTS: Intravesical infusion of 3 mM menthol
      reduced VV by 20%, VT by 19%, and PT by 31%. RV, VE, and MP were unaltered.
      Capsaicin pretreatment had no effect on baseline cystometric parameters, and 3 mM
      menthol caused similar reductions in VV (24%), VT (22%), and PT (30%), while
      having no effect on RV, VE, and MP. Menthol at 0.1, 0.3, and 1 mM inhibited
      carbachol-induced contractions by 10.7%, 36.7%, and 97.3%, respectively.
      CONCLUSIONS: Our results demonstrated that intravesical infusion of menthol
      facilitated the micturition reflex, and capsaicin pretreatment had no effect on
      this response. Menthol inhibited carbachol-induced contraction of the detrusor
      smooth muscle. This suggests that intravesically infused menthol cannot relax
      detrusor muscle, and acts on capsaicin-resistant afferents (probably through
      TRPM8 in urothelium or sensory nerve endings) to facilitate the micturition
      reflex.

PMID- 18336881
TI  - Removal of retained Foley catheter in bladder with novel use of ureteral
      catheter: lasso technique.
AB  - Numerous and varied foreign bodies have been described in the lower urinary
      tract. Techniques previously used to remove these objects have included open and
      endoscopic removal. We present a novel endoscopic technique using a ureteral
      catheter as a lasso to remove a retained foreign body, in this case a retained
      Foley catheter.

PMID- 18336882
TI  - Pathologic concordance of sporadic synchronous bilateral renal masses.
AB  - OBJECTIVES: To review the collective experience evaluating pathologic concordance
      rates of sporadic bilateral synchronous renal tumors reported in the
      Surveillance, Epidemiology, and End Results (SEER) database and the published
      English literature and treated at Fox Chase Cancer Center; specifically, to
      analyze concordance rates of malignant versus benign disease, histologic type,
      tumor stage, and nuclear grade. METHODS: We reviewed the SEER database, the
      published English language literature, and our own institutional tumor registry
      to identify all cases of sporadic, synchronous localized (cT1-3N0M0) bilateral
      renal masses. Malignant and benign concordance rates were defined as agreement of
      any benign or malignant tumor type bilaterally. Histologic concordance was
      defined as bilateral histologic agreement. Tumors with mixed histologies were
      discordant unless all patterns were identical bilaterally. Nuclear grades were
      concordant if bilateral tumors were either "high" grade or "low" grade. RESULTS:
      The malignant concordance rate in the SEER data was 99% (273 of 274), and benign
      concordance was 0 (0 of 1). In the published literature and Fox Chase Cancer
      Center series, malignant concordance rates ranged from 84% to 95%, whereas benign
      concordance ranged from 39% to 67%. The SEER data revealed a histologic
      concordance rate of 93% (256 of 274), and nuclear grade concordance was 85% (88
      of 103). CONCLUSIONS: These data demonstrate that in cases of bilateral sporadic
      localized synchronous renal masses, a diagnosis of ipsilateral renal cell
      carcinoma is associated with contralateral renal cell carcinoma in the vast
      majority of patients, whereas ipsilateral benign pathology is associated with
      contralateral benign disease at a substantially lower rate. Histologic
      concordance is similarly high, meaning most cases of clear cell or papillary
      tumors ipsilaterally are concordant in the contralateral kidney. Concordance
      rates of nuclear grade were slightly lower. These data are important when
      counseling and managing patients with bilateral synchronous sporadic renal
      tumors.

PMID- 18336883
TI  - Port site and local recurrence of incidental solitary renal plasmacytoma after
      retroperitoneoscopic radical nephrectomy.
AB  - Port site and local recurrences are rather rare, especially after laparoscopic
      excision of renal malignancies. In addition to the known risk factors, including
      inappropriate surgical technique and specimen removal, the tumor biology is
      important. Renal plasmacytomas are rare manifestations of plasma cell tumors. We
      report a case of port site and local tumor recurrence of a solitary renal
      plasmacytoma after retroperitoneoscopic radical nephrectomy without any known
      risk factors, other than the aggressive tumor biology itself.

PMID- 18336884
TI  - Combined buccal mucosa graft and dorsal penile skin flap for repair of severe
      hypospadias.
AB  - OBJECTIVES: Urethral reconstruction in severe hypospadias presents a great
      challenge. We have designed a method of combining a longitudinal dorsal island
      skin flap and buccal mucosa graft to create a neourethra in most severe
      hypospadias. METHODS: Between January 2003 and March 2007, 17 patients (aged from
      9 to 23 months) underwent severe hypospadias repair (13 penoscrotal and 4 scrotal
      hypospadias). Short urethral plate was divided in all cases and remaining
      curvature repaired by dorsal plication. We harvested and fixed a buccal mucosa
      graft to the ventral side of corpora cavernosa to be the first half of a
      neourethra. A longitudinal dorsal island skin flap was created and buttonholed
      ventrally. We sutured it together with the buccal mucosa graft to form the
      neourethra. We fixed the abundant flap pedicle laterally to cover all suture
      lines of the neourethra. We performed penile skin reconstruction using available
      penile skin. RESULTS: The mean (range) follow-up was 25 (7 to 58) months. We
      achieved satisfactory, functional, and aesthetic results in 14 patients. In 3
      cases urethral fistula (2) and distal stricture (1) required secondary treatment.
      CONCLUSIONS: Combined longitudinal island skin flap and buccal mucosa graft could
      be a good choice for urethral reconstruction in most severe hypospadias repairs.

PMID- 18336885
TI  - Effect of being overweight on stone-forming risk factors.
AB  - OBJECTIVES: To evaluate the possible role of being overweight on stone-forming
      risk factors. METHODS: A total of 264 patients were included in the study. After
      a detailed stone disease history, the systolic and diastolic blood pressure was
      precisely measured and recorded for all patients, and the body mass index, 24
      hour urine composition, and serum stone-forming risk parameters were evaluated in
      overweight (n = 164; 52 men and 112 women; group 1) and normal (n = 100; 44 men
      and 56 women, group 2) patients. Of the 264 patients, 110 were men and 154 were
      women (male/female ratio 1:1.4); none had undergone any medical or dietetic
      treatment before study entry. RESULTS: The evaluation of the stone-forming risk
      factors in both groups revealed that obesity increased the excretion of these
      substances in group 1. Of the 164 patients in group 1, most (58; 35.3%)
      demonstrated hyperoxaluria compared with group 2 (P <0.001). Also, the mean
      urinary oxalate level was 44.91 +/- 24.89 mg/24 hours in group 1 and was 26.67 +/
      24.59 mg/24 hours in group 2 (P <0.001). Similarly, patients in group 1 had
      elevated mean urinary calcium excretion and lower citrate excretion compared with
      those in group 2 (P = 0.045 and P = 0.032, respectively). CONCLUSIONS: Our
      results have clearly shown that being overweight might be associated with an
      elevated risk of stone formation in both sexes owing to alterations in urine
      composition. People who are overweight could be more prone to stone formation and
      should be carefully evaluated and followed up regarding this aspect.

PMID- 18336886
TI  - Effects of laparoscopy on surgical discharge practice patterns.
AB  - OBJECTIVES: The length of stay (LOS) after surgical procedures often varies
      regionally and reflects local idiosyncratic practice patterns. We sought to
      elicit the influence of local pressures (in the form of the technologic
      imperative exerted by laparoscopy) on discharge physician practice style as
      measured by LOS. METHODS: Patients undergoing prostatectomy, nephrectomy, and
      hysterectomy in 2003 were identified from the Nationwide Inpatient Sample using
      the International Classification of Diseases, Ninth Revision, codes. Within each
      procedure, the laparoscopy volume was measured and sorted into tertiles. Patients
      remaining in the hospital longer than the 90th percentile after each surgery were
      excluded to minimize the influence of imperative indications on LOS. For each
      procedure, generalized linear models were used to measure the relationship
      between the hospital laparoscopy volume and log-transformed LOS outcomes among
      patients undergoing conventional surgery. RESULTS: In 2003, 2%, 19%, and 16% of
      patients underwent laparoscopic prostatectomy, nephrectomy, and hysterectomy,
      respectively. A hospital's laparoscopy and conventional volumes were moderately
      to highly correlated for hysterectomy (r = 0.65) and nephrectomy (r = 0.58) and
      less so for prostatectomy (r = 0.24). Among patients undergoing conventional
      prostatectomy and nephrectomy, those treated at high-volume laparoscopy hospitals
      had 0.41 and 0.30 fewer hospital days, respectively, compared with those treated
      at hospitals at which only conventional surgery was performed (both P <0.05).
      This effect was partially explained by a hospital's open procedure volume (both P
      = 0.07). Similar relationships were not evident for hysterectomy. CONCLUSIONS:
      These data highlight that patients treated by conventional methods at high-volume
      laparoscopy centers have shorter hospital stays and suggest that physician
      practices might susceptible to external influences such as the technologic
      imperative.

PMID- 18336887
TI  - Gene expression of survivin and its spliced isoforms associated with
      proliferation and aggressive phenotypes of prostate cancer.
AB  - OBJECTIVES: To assess the effect of survivin gene expression on the proliferation
      of prostate cancer (PCa) cells and study the association of suvivin and its
      spliced isoforms gene expression levels with the pathologic grade of PCa.
      METHODS: Gene expression of survivin and its spliced isoforms in the LNCaP and PC
      3 PCa cell lines was determined using reverse transcriptase-polymerase chain
      reaction. We knocked down the gene expression of survivin using small interfering
      RNA and assessed the cell proliferation using the MTS assay. Next, we quantified
      the gene expression levels of survivin and its isoforms in prostate biopsy
      samples (PCa, n = 37; benign prostatic hyperplasia, n = 13; PCa after androgen
      deprivation therapy, n = 12) using the quantitative real-time polymerase chain
      reaction method. RESULTS: In PCa cells, survivin and survivin-2alpha and survivin
      2B were expressed more than survivin-DeltaEx3. The decrease in survivin gene
      expression by transfection of siRNA was accompanied by the inhibition of cell
      proliferation of PCa cells (31% and 25% decreased in LNCaP and PC-3 cells, P
      <0.01). In the prostate biopsy samples, the survivin expression in PCa was
      significantly greater than that in BPH or PCa after androgen deprivation therapy
      (PCa, 1; BPH, 0.16; PCa after androgen deprivation therapy, 0.27; P <0.01). In
      the PCa samples, the survivin expression level was associated significantly with
      high-grade cancer (Gleason score 8 or 9; Gleason score 7 versus 8 or 9, 1 versus
      2.00, respectively; P <0.05). The survivin-2B/survivin ratio in high-grade cancer
      was lower than that in low-grade (Gleason score 7) cancer (Gleason score 7 versus
      8 or 9, 1 versus 0.69; P <0.10). CONCLUSIONS: These findings suggest that
      survivin and its spliced isoforms have associations with PCa cell proliferation
      and aggressive phenotypes.

PMID- 18336888
TI  - The electromagnetic detection of prostatic cancer: evaluation of diagnostic
      accuracy.
AB  - OBJECTIVES: To evaluate the accuracy of the TRIMprob in the diagnosis of prostate
      neoplasm. METHODS: Consecutive patients referred for prostate biopsy were
      prospectively enrolled. Patients had history taken, physical examination by
      digital rectal examination (DRE) of the prostate, assessment of total and free
      serum prostate-specific antigen (PSA) levels, prostate transrectal
      ultrasonography (TRUS), and TRIMprob test. Indications for prostate biopsy
      included one or more of the following conditions: total serum PSA levels of 4.0
      ng/mL or more, free/total serum PSA ratio of 0.18 or less, positive results on
      DRE, and suspicious findings on TRUS. Twelve-core, TRUS-guided biopsies were
      performed with local anesthesia. A blinded investigator performed the TRIMprob
      test; the lowest value of the signal at 465 MHz was looked for and recorded,
      although data of the electromagnetic signal at 930 and 1295 MHz were also
      recorded. RESULTS: One hundred eleven patients (aged 64.9 +/- 8.1 years, mean +/-
      standard deviation), enrolled between November 2004 and August 2005, were
      analyzed. Total serum PSA level was 8.4 +/- 3.6 ng/mL, and free/total serum PSA
      ratio was 0.15 +/- 0.7. TRIMprob sensitivity for the diagnosis of prostate cancer
      was 0.86%; specificity and positive and negative predictive values were 0.60 and
      0.88; accuracy was 72%. TRIMprob accuracy outperformed any other diagnostic
      parameter considered, including the rule of chance. The association of TRIMprob
      and DRE offered a sensitivity and a negative predictive value of 0.86% or
      greater. CONCLUSIONS: TRIMprob had the highest accuracy rate, among all other
      tests, for the diagnosis of prostate cancer. Electromagnetic detection with the
      TRIMprob test seems to be a promising technology and a useful additional tool for
      the early detection of prostate cancer.

PMID- 18336889
TI  - Xanthogranulomatous orchitis in a patient with a history of instrumentation and
      bacillus Calmette-Guerin therapy.
AB  - Xanthogranulomatous orchitis (XGO) is a rare histological finding that is
      generally diagnosed at orchiectomy. To date, fewer than 10 reports of XGO exist
      in the literature. The exact pathogenesis of XGO is unknown and patients may
      present with a rapid onset of symptoms or a longer, more indolent course. We
      report a patient who presented with symptoms of epididymoorchitis, leukocytosis,
      and fever after an instillation of bacillus Calmette-Guerin therapy for bladder
      cancer.

PMID- 18336890
TI  - XRCC1 genetic polymorphisms and bladder cancer susceptibility: a meta-analysis.
AB  - OBJECTIVES: To examine the association between three x-ray repair cross
      complementing group 1 (XRCC1) genetic polymorphisms (Arg(194)Trp, Arg(280)His,
      and Arg(399)Gln) and bladder cancer susceptibility. METHODS: A comprehensive
      search was conducted to identify all case-control studies of XRCC1 polymorphisms
      and bladder cancer risk. Statistical analysis was performed with the software
      program Review Manage, version 4.2. RESULTS: A total of 10 eligible reports,
      including 3749 cases and 3947 controls, were identified. For Arg(194)Trp (six
      studies, 3091 cases, 3219 controls), no evidence indicated that individuals
      carrying the variant genotypes (Trp/Trp + Arg/Trp), relative to those carrying
      the wild homozygote Arg/Arg genotype, had a decreased risk of bladder cancer
      (odds ratio [OR] 0.90, 95% confidence interval [CI] 0.77 to 1.05; P = 0.17). For
      Arg(280)His (three studies, 2547 cases, 1784 controls), individuals with
      His/His+Arg/His genotypes had no significant risk of bladder cancer, compared
      with those with the Arg/Arg genotype (OR 0.99, 95% CI 0.55 to 1.77; P = 0.97).
      For Arg(399)Gln (10 studies, 3729 cases, 3927 controls), the Gln/Gln genotype
      carriers did not have a decreased cancer risk compared with those individuals
      with the Arg/Arg genotype (OR 0.95, 95% CI 0.82 to 1.10; P = 0.48). Similarly, no
      associations were found in the recessive and dominant modeling (Gln/Gln versus
      Arg/Gln+Arg/Arg: OR 0.92, 95% CI 0.80 to 1.05; P = 0.23; Arg/Gln+Gln/Gln versus
      Arg/Arg: OR 1.04, 95% CI 0.95 to 1.14; P = 0.36). CONCLUSIONS: No association was
      found between the polymorphisms in XRCC1 (Arg(194)Trp, Arg(280)His, Arg(399)Gln)
      and bladder cancer susceptibility.

PMID- 18336891
TI  - Venlafaxine reverses chronic fatigue-induced behavioral, biochemical and
      neurochemical alterations in mice.
AB  - A state of chronic fatigue was produced in mice by subjecting them to forced swim
      inside a rectangular jar of specific dimensions everyday for a 6 min session for
      15 days. Immobility period was recorded on alternate days. The effect of
      venlafaxine, a dual reuptake inhibitor of serotonin and norepinephrine was
      evaluated in this murine model of chronic fatigue. Venlafaxine was administered
      daily and on the days of testing, it was injected 30 min before forced swim
      session. On the 16th day i.e. 24 h after the last dose of venlafaxine, various
      behavioral, biochemical and neurotransmitter estimations in the brain were
      carried out. There was a significant increase in immobility period in vehicle
      treated mice on successive days, the maximum immobility score reaching on the 7th
      day and sustained till 15th day. Behavioral parameters revealed hyperlocomotion,
      anxiety response, muscle incoordination, hyperalgesia and memory deficit.
      Biochemical analysis showed a significant increase in lipid peroxidation, nitrite
      and myeloperoxidase levels and a decrease in the reduced glutathione (GSH) levels
      in brain homogenates. Further, there was a decrease in adrenal ascorbic acid
      following chronic forced swim. The neurotransmitter estimations in the brain
      samples revealed a decrease in norepinephrine, serotonin and dopamine levels on
      chronic exposure to forced swim for 15 days. Daily treatment with venlafaxine (8
      and 16 mg/kg, i.p.) for 15 days produced a significant reduction in immobility
      period and reversed various behavioral, biochemical and neurotransmitter
      alterations induced by chronic fatigue. Venlafaxine could be of therapeutic
      potential in the treatment of chronic fatigue.

PMID- 18336892
TI  - Adolescents report both positive and negative consequences of experimentation
      with cigarette use.
AB  - OBJECTIVE: To examine the physiological and social consequences that 9th and 10th
      grade adolescents experience as a result of experimenting with cigarette use, and
      whether consequences vary by level of experimentation and gender. METHOD: Data
      were collected between 2001 and 2004 from 395 adolescents attending two northern
      California public high schools. Analyses are limited to 155 adolescents who
      reported puffing on cigarettes or smoking whole cigarettes at any of four time
      points during the study. RESULTS: The percentage of adolescents reporting
      consequences of smoking was as follows: any positive consequence (56%), felt
      relaxed (46%), looked cool (31%), looked grown-up (27%), became popular (17%),
      any negative consequence (56%), friends were upset (35%), trouble catching breath
      (29%), bad cough (26%), and got into trouble (23%). Ten percent of adolescents
      reported only experiencing negative consequences, 11% reported only positive
      consequences, 45% reported both negative and positive consequences, and 34%
      reported no consequences. Greater levels of experimentation were associated with
      greater likelihood of reporting positive or negative consequences. Few gender
      differences emerged. CONCLUSION: Adolescents experience both positive and
      negative consequences of experimentation with cigarette use. Prevention and
      intervention efforts should acknowledge that positive consequences of smoking may
      occur and address how these consequences can be achieved through other behaviors.

PMID- 18336893
TI  - In vitro embryo production in buffalo (Bubalus bubalis) using sexed sperm and
      oocytes from ovum pick up.
AB  - The objective was to explore the use of sexed sperm and OPU-derived oocytes in an
      IVP system to produce sex-preselected bubaline embryos. Oocytes were recovered
      from 20 fertile Murrah and Nili-Ravi buffalo cows by repeated (twice weekly)
      ultrasound-guided transvaginal ovum pick up (OPU), or by aspiration of abbatoir
      derived bubaline ovaries, and subjected to IVF, using frozen-thawed sexed or
      unsexed bubaline semen. On average, 4.6 oocytes were retrieved per buffalo per
      session (70.9% were Grades A or B). Following IVF with sexed sperm, oocytes
      derived from OPU had similar developmental competence as those from abattoir
      derived ovaries, in terms of cleavage rate (57.6 vs. 50.4%, P=0.357) and
      blastocyst development rate (16.0 vs. 23.9%, P=0.237). Furthermore, using frozen
      thawed sexed versus unsexed semen did not affect rates of cleavage (50.5 vs.
      50.9%, P=0.978) or blastocyst development (15.3 vs. 19.1%, P=0.291) after IVF
      using OPU-derived oocytes. Of the embryos produced in an OPU-IVP system, 9 of 34
      sexed fresh embryos (26.5%) and 5 of 43 sexed frozen embryos (11.6%) transferred
      to recipients established pregnancies, whereas 7 of 26 unsexed fresh embryos
      (26.9%) and 6 out of 39 unsexed frozen embryos (15.4%) transferred to recipients
      established pregnancies. Eleven sex-preselected buffalo calves (10 females and
      one male) and 10 sexed buffalo calves (six females and four males) were born
      following embryo transfer. In the present study, OPU, sperm sexing technology,
      IVP, and embryo transfer, were used to produce sex-preselected buffalo calves.
      This study provided proof of concept for further research and wider field
      application of these technologies in buffalo.

PMID- 18336894
TI  - Ovsynch synchronization and fixed-time insemination in goats.
AB  - This study assessed the efficacy of an Ovsynch protocol (vs. the classical
      cronolone containing vaginal sponge+eCG treatment) to generate fixed-time
      insemination in goats during the breeding season. Each regimen was applied to 24
      Boer goat does. Onset and duration of estrus were determined with an aproned male
      and follicular development was monitored by ultrasonography. Ovulation and
      quality of the corpora lutea were established from progesterone concentrations.
      In 10-11 goats per group, LH concentrations were determined throughout the
      preovulatory period. Does were inseminated at pre-determined times (16 h after
      the second GnRH injection and 43 h after sponge removal). Estrus was identified
      in 96% of the Ovsynch-treated goats (at 49 h after prostaglandin injection) and
      in 100% of the goats synchronized with sponges (at 37 h after sponge removal).
      Low progesterone concentrations at the time of AI were observed in 21/24 and
      24/24 goats synchronized by Ovsynch and sponges, respectively. Synchronization of
      the LH surge was tighter following Ovsynch compared to sponge treatment. Kidding
      rates (at 58 and 46% in the Ovsynch and sponge groups, respectively) and
      prolificacy (at 1.86 and 1.83 in the Ovsynch- and sponge-treated goats) were
      similar for both groups, as were the number of ovulations (2.9 and 3.3) and the
      proportion of does with premature corpus luteum regression (29 and 17%). When
      excluding does with premature luteal regression and those with low progesterone
      levels when receiving prostaglandins, kidding rate reached 87.5% (14/16) after
      Ovsynch. During the breeding season, the Ovsynch protocol may thus be an useful
      alternative to the sponge-eCG treatment.

PMID- 18336895
TI  - Effects of re-infection with Neospora caninum in bulls on parasite detection in
      semen and blood and immunological responses.
AB  - Three bulls with experimentally induced primary infection with Neospora caninum
      were re-infected intravenously with 10(8) live N. caninum tachyzoites of the NC-1
      isolate at 300 days post-infection to investigate the presence of N. caninum in
      semen and blood, and the associated immune responses. In parallel, three bulls
      with experimentally induced primary infection with N. caninum and three non
      infected bulls were also monitored. Re-infected and infected bulls showed an
      intermittent presence of N. caninum DNA in semen with a parasite load ranging
      from 0.1 to 15.6 (mean 4.4) and 0.1 to 11.1 (mean 4.1) parasites/ml,
      respectively. Re-infected bulls showed significant and persistent serum-specific
      IgM and IgG antibody responses. Specific IgG levels were detected in seminal
      plasma of all infected bulls, but the magnitude of the response was significantly
      higher in re-infected rather than in chronically infected animals. The mean
      specific IFN-gamma levels in re-infected bulls were significantly increased as
      early as 3 and 7 days after experimental infection when compared to bulls in
      other groups. This study showed that the intermittent presence and parasite load
      of N. caninum in the semen of re-infected bulls is very similar to that reported
      in chronically infected animals. The protozoa could not be isolated from BALB/c
      nu/nu mice inoculated with PCR-positive semen samples and inseminated heifers
      with pooled semen samples did not show seroconversion. Plasma IFN-gamma level
      seems to be a good indicator of a recent N. caninum infection.

PMID- 18336896
TI  - Ovarian function in Nelore (Bos taurus indicus) cows after post-ovulation
      hormonal treatments.
AB  - Maternal recognition of pregnancy in the cow requires successful signaling by the
      conceptus to block luteolysis. Conceptus growth and function depend on an optimal
      uterine environment, regulated by luteal progesterone. The objective of this
      study was to test strategies to optimize luteal function, as well as prevent a
      dominant follicle from initiating luteolysis. Nelore (Bos taurus indicus) beef
      cows (n=40) were submitted to a GnRH/PGF(2alpha)/GnRH protocol. Cows that
      ovulated from a dominant ovarian follicle (ovulation=Day 0) were allocated to
      receive: no additional treatment (G(C); n=7); 3000IU of hCG on Day 5 (G(hCG);
      n=5); 5mg of estradiol-17beta on Day 12 (G(E2); n=6); or 3000IU of hCG on Day 5
      and 5mg of estradiol-17beta on Day 12 (G(hCG/E2); n=5). Ultrasonographic imaging
      of the ovaries, assessment of plasma progesterone concentration, and detection of
      estrus were done daily from Day 5 to the day of subsequent ovulation. Treatment
      with hCG induced an accessory CL, increased CL volume, and plasma progesterone
      concentration throughout the luteal phase (P<0.01). Estradiol-17beta induced
      atresia and recruitment of a new wave of follicular growth; it eliminated a
      potentially estrogen-active, growing ovarian follicle within the critical period
      for maternal recognition of pregnancy, but it also hastened luteolysis (Days 16
      or 17 vs. Days 18 or 19 in non-treated cows). In conclusion, the approaches
      tested enhanced luteal function (hCG) and altered ovarian follicular dynamics
      (estradiol-17beta), but were unable to extend the life-span of the CL in Nelore
      cows.

PMID- 18336897
TI  - Successful fertilization of Varicorhinus macrolepis eggs with sperm subjected to
      two freeze-thaw cycles.
AB  - Although sperm from several fish species have been successfully cryopreserved,
      few studies have been done in small and/or endangered species. The aim of the
      present work was to develop a method of freezing and refreezing Varicorhinus
      macrolepis semen in 1.8 mL cryovials. The effect of extenders and cryoprotectants
      on the motility of post-thaw sperm was examined. The motility of frozen-thawed
      sperm in extender D-15 was higher than that in MPRS and fish Ringer solution
      (P<0.05). Dimethyl sulfoxide (DMSO) and glycerol provided greater protection to
      sperm than methanol during freezing and thawing; the most effective concentration
      of DMSO and glycerol was 10%. The fertilization rate of frozen-thawed sperm was
      not significantly different from that of fresh sperm. Furthermore, mean (+/-S.D.)
      hatching rate did not differ significantly between frozen-thawed (82.7+/-12.4%)
      and fresh sperm (90.7+/-4.5%). Although frozen-thawed sperm that was immediately
      refrozen had 0% post-thaw motility, frozen semen that was refrozen after dilution
      with D-15 (containing DMSO at a ratio of 1:2) had post-thaw motility of 38.3+/
      2.9%. Motility was lower for refrozen than for frozen sperm (P<0.05).
      Furthermore, fertilization and hatching rates of refrozen sperm were 42.9+/-6.7
      and 34.1+/-10.5%, respectively, which were lower than that of fresh sperm
      (P<0.05).

PMID- 18336898
TI  - Cytotoxicity of silica-glass fiber reinforced composites.
AB  - OBJECTIVES: Silica-glass fiber reinforced polymers can be used for many kinds of
      dental applications. The fiber reinforcement enhances the mechanical properties
      of the polymers, and they have good esthetic attributes. There is good initial
      bonding of glass fibers to polymers via an interface made from silane coupling
      agents. The aim of this in vitro study was to determine the cytotoxicity of two
      polymers reinforced with two differently sized silica-glass fibers before and
      after thermal cycling. Cytotoxicity of the polymers without fibers was also
      evaluated. METHODS: Two different resin mixtures (A and B) were prepared from
      poly(vinyl chloridecovinylacetate) powder and poly(methyl methacrylate) (PMMA)
      dissolved in methyl methacrylate and mixed with different cross-linking agents.
      The resin A contained the cross-linking agents ethylene glycol dimethacrylate and
      1,4-butanediol dimethacrylate, and for resin B diethylene glycol dimethacrylate
      was used. Woven silica-glass fibers were used for reinforcement. The fibers were
      sized with either linear poly(butyl methacrylate)-sizing or cross-linking PMMA
      sizing. Cytotoxicity was evaluated by filter diffusion test (ISO 7405:1997) of
      newly made and thermocycled test specimens. Extracts were prepared according to
      ISO 10993-12 from newly made and from thermocycled specimens and tested by the
      MTT assay. The results from the experiments were statistically analyzed by one
      way ANOVA and Tukey's test (rho<0.05). RESULTS: The filter diffusion test
      disclosed no change in staining intensity at the cell-test sample contact area
      indicating non-cytotoxicity in all experimental groups. Cell viability assessed
      by MTT assay was more than 90% in all experimental groups. All are non-cytotoxic.
      SIGNIFICANCE: It can be concluded that correctly processed heat polymerized
      silica-glass fiber reinforced polymers induced no cytotoxicity and that
      thermocycling did not alter this property.

PMID- 18336899
TI  - The electrochemical behavior and surface analysis of Ti50Ni47.2Co2.8 alloy for
      orthodontic use.
AB  - OBJECTIVES: The aim of this study was to investigate the electrochemical behavior
      of Ti50Ni47.2Co2.8 alloy in deaerated artificial saliva solutions with binary
      NiTi alloy as reference and to characterize the composition and structure of the
      passive film after polarization tests. METHODS: The corrosion behavior of NiTiCo
      alloy was systematically studied by open circuit potential, potentiodynamic and
      potentiostatic techniques. The surface characterization after anodic polarization
      tests were demonstrated by XPS. The electrolytes were maintained at 37 degrees C
      by immersing the test cell in water bath. 500 mV vs. SCE was applied on the
      samples for potentiostatic tests. The metal ions concentration was measured by
      ICP/OES. RESULTS: Potentiodynamic and potentiostatic tests results showed that
      the corrosion behavior of NiTiCo was similar to that of NiTi alloy. With the
      increase of pH value of the electrolytes, both corrosion potential (Ecorr) and
      pitting corrosion potential (Eb) decreased. XPS results revealed that the outmost
      passive film consisted mainly of TiO2 which were identical with that of NiTi
      alloy. The Ni ion release amount of NiTiCo was very close to that of NiTi alloy
      as examined by ICP/OES. Neither Ti nor Co ion was detected due to the detection
      limitation. SIGNIFICANCE: The corresponding relationship between corrosion
      behavior and pH value of the artificial saliva should be taken into consideration
      during the application of orthodontic wires. The addition of Co had little effect
      on the corrosion behavior of NiTi as well as the formation of the passive film.

PMID- 18336900
TI  - Computer aided analysis of digitized dental stone replicas by dental CAD/CAM
      technology.
AB  - OBJECTIVES: To determine the reproducibility of digitized dental stone replicas
      compared to the master model and the reliability of the computer aided analysis.
      METHODS: Four master dies, prepared for complete crowns were fabricated in
      presintered yttria-stabilized tetragonal zirconia (Y-TZP). Eight vinyl
      polysiloxane impressions (PROVIL novo; Heraeus Kulzer) were taken of each die and
      stone replicas were poured in type IV stone (Vel-Mix Stone; Kerr). The master
      dies and the stone replicas were digitized in a touch-probe scanner (Procera
      Forte; Nobel Biocare AB), to create triangulated surface-models. The point-cloud
      from the first of the repeated digitizations of each master die was used as CAD
      reference-models (CRM). Discrepancies between the points in the triangulated
      surface-models and the corresponding CRM were measured by a matching-software
      (CopyCAD 6.504 SP2; Delcam Plc). The distribution of the discrepancies was
      analyzed and presented in color-difference-maps. RESULTS: The precision of the
      measuring method, presented as the repeatability coefficient, ranged between 7
      and 16 microm (entire surface), whereas the analysis of the stone replicas
      revealed a precision (repeatability coefficient) ranging from 19 to 26 microm.
      The accuracy of the replica to master (the mean discrepancy) ranged from 0.5 to
      2.0 microm (95% confidence interval 1.5-2.9 microm). SIGNIFICANCE: The greatest
      precision of the measurement was seen in the jacket surface of the die. The size
      of the stone replicas varied and the repeatability coefficient was on average 15
      microm (2-25 microm) greater for the replica-to-master alignment than the
      repeated digitizations of the master.

PMID- 18336901
TI  - Chaperone activities of bovine and camel beta-caseins: Importance of their
      surface hydrophobicity in protection against alcohol dehydrogenase aggregation.
AB  - Beta-casein (beta-CN) showing properties of intrinsically unstructured proteins
      (IUP) displays many similarities with molecular chaperones and shows anti
      aggregation activity in vitro. Chaperone activities of bovine and camel beta-CN
      were studied using alcohol dehydrogenase (ADH) as a substrate. To obtain an
      adequate relevant information about the chaperone capacities of studied caseins,
      three different physical parameters including chaperone constant (k(c), microM(
      1)), thermal aggregation constant (k(T), degrees C(-1)) and aggregation rate
      constant (k(t), min(-1)) were measured. Bovine beta-CN displays greater chaperone
      activity than camel beta-CN. Fluorescence studies of 8-anilino-1
      naphthalenesulfonic acid (ANS) binding demonstrated that bovine beta-CN is doted
      with larger effective hydrophobic surfaces at all studied temperatures than camel
      beta-CN. Greater relative hydrophobicity of bovine beta-CN than camel beta-CN may
      be a factor responsible for stronger interactions of bovine beta-CN with the
      aggregation-prone pre denatured molecular species of the substrate ADH, which
      resulted in greater chaperone activity of bovine beta-CN.

PMID- 18336902
TI  - Long-term bone tissue reaction to polyethylene oxide/polybutylene terephthalate
      copolymer (Polyactive) in metacarpophalangeal joint reconstruction.
AB  - The poly-L/D-lactide 96/4 joint scaffolds are used to engineer fibrous tissue
      joints in situ for the reconstruction of metacarpophalangeal joints. In this
      experimental study, a supplementary elastomeric stem made of Polyactive
      1000PEO70PBT30 (a segmented block copolymer of polyethylene oxide and
      polybutylene terephtalate with 70/30 PEO/PBT ratio) was used to anchor the joint
      scaffold in the arthroplasty space. Eleven resected fifth metacarpophalangeal
      joints of minipig were reconstructed and evaluated radiologically and
      histologically for 3 years. Plain joint scaffold and Swanson silicone implant
      arthroplasties (11 of each) in metacarpophalangeal joints of minipig served as
      controls. Altogether fore limbs of eighteen minipigs were operated for the study.
      Deleterious tissue reaction with dramatic signs of osteolysis and inflammatory
      foreign-body reaction was observed around the Polyactive stems. The mean maximum
      diameter of the osteolytic stem cavity was statistically wider when compared to
      the mean maximum diameter of Swanson implant group during the first postoperative
      year. Numerous osteoclasts were found at the margins of the osteolytic areas. No
      direct bone contact could be seen. At 1 year osteoblastic regeneration and
      formation of new trabecular bone followed. Finally the foreign-body reaction
      settled, but the adjoining bones were at this stage highly sclerotic and composed
      of coarse trabeculae. In contrary to previous in vivo studies suggesting
      biocompatibility, osteoconductivity and capability to bond to bone, Polyactive
      1000PEO70PBT30 stem in this setting caused massive osteolytic lesions and foreign
      body reactions.

PMID- 18336903
TI  - Characterisation of tone oscillations in placental and myometrial arteries from
      normal pregnancies and those complicated by pre-eclampsia and growth restriction.
AB  - Agonist-induced tone oscillations (rhythmic contractions and relaxations) occur
      in vascular beds to allow acute regulation of volume flow and thus the delivery
      of oxygen and nutrients to the tissue. Mechanisms responsible for the control of
      human placental vasomotor tone and blood flow are poorly characterized. This
      study aimed to characterise thromboxane-induced tone oscillations in human
      placental and myometrial arteries. Chorionic plate and myometrial arteries
      obtained from biopsies at term were mounted for isometric tension measurement.
      Tone oscillations were observed in chorionic arteries only when exposed to sub
      maximal (<1 microM) concentrations of U46619. Slow (mean+/-SEM) frequency (2.6+/
      0.5 per hour), large amplitude (39+/-7% of peak contraction) tone oscillations
      were elicited by 0.03 microM U46619 (n=18). In the presence of the nitric oxide
      synthase (NOS) inhibitor l-NNA (100 microM) the amplitude was significantly
      reduced (40+/-13% to 18+/-8%, P<0.05, n=6), frequency was unaltered and the
      bradykinin-dependent vasodilator response was reduced (68+/-13% to 40+/-19%,
      P<0.05, n=6). Myometrial arteries exposed to 1 microM U46619 developed tone
      oscillations within 10 min, which increased in amplitude over 30min occurring at
      relatively constant frequency. The mean amplitude of oscillations at 30 min (31+/
      7%, n=16) was similar to that in chorionic arteries but the occurrence more
      frequent (42.8+/-9.7 per hour, P<0.001). Inhibition of NOS did not alter tone
      oscillations in myometrial arteries. Tone oscillations in chorionic arteries from
      pre-eclamptic and growth restricted (FGR) pregnancies were reduced in amplitude
      whereas those in myometrial arteries had increased frequency. Inhibition of NOS
      further reduced oscillation amplitude in chorionic arteries from FGR pregnancies.
      The alterations may contribute to the vasculopathology of these conditions, or,
      may represent compensatory mechanisms to maintain a matching of materno-placental
      blood flow.

PMID- 18336904
TI  - Antioxidant effect of propolis against exposure to propetamphos in rats.
AB  - In the present study, each group comprised six animals, and a total of 30 female.
      Wistar Albino rats weighing 200-250g were used. The first group served as the
      control group. Group 2 received propolis at a concentration of 100mg/kgbw/day in
      drinking water. Groups 3 and 4 were administered propetamphos at doses of 7.5 and
      15.0mg/kgbw/day, respectively, in drinking water. Group 5 was treated with
      propetamphos at a dose of 15.0mg/kgbw/day, in association with 100mg/kgbw/day
      propolis in drinking water. Treatment was continued for 28 days, and at the end
      of this period, blood and tissue (liver, kidney and brain) samples were
      collected. Plasma and tissue MDA levels and erythrocyte and tissue SOD, CAT, and
      GSH-Px activities were measured. In conclusion, the administration of propolis
      was concluded to exhibit antiradical and antioxidant effect, and thereby to
      result in the alleviation of oxidative stress.

PMID- 18336905
TI  - Comparative ecotoxicity of three polluted industrial soils for the Collembola
      Folsomia candida.
AB  - We tried to quantify the ecotoxicity of three industrial soil samples
      contaminated by different metals, using the Collembolan Folsomia candida as a
      biological model and mortality, growth and reproduction as parameters. The
      observed ecotoxicities are rather normal for the first such soil sample (aluminum
      factory) but are high for the second sample (ore treatment) and relatively low
      for the third one (zinc factory) considering its high metal concentrations. For
      these last two soil samples, an unusual ecotoxicity plotting is observed: two
      high ecotoxicity recordings fit with a low and high percentage of polluted soil
      to non-polluted soil and noticeably lower ecotoxicity recordings are observed
      between them. Chemical analyses of metals in pore waters show that arsenic
      probably explains part of such an unusual ecotoxicity curve. Otherwise, mortality
      and growth of the animals are less sensitive parameters than reproduction. Our
      experiments show that the results of the ecotoxicological assays of polluted
      soils are complex and difficult to interpret.

PMID- 18336906
TI  - A framework of operating models for interdisciplinary research programs in
      clinical service organizations.
AB  - A framework of operating models for interdisciplinary research programs in
      clinical service organizations is presented, consisting of a "clinician
      researcher" skill development model, a program evaluation model, a researcher-led
      knowledge generation model, and a knowledge conduit model. Together, these models
      comprise a tailored, collaborative approach to enhancing research-informed
      practice in community-based clinical service organizations. The models place
      different degrees of emphasis on the development of research-related skills in
      practitioners, the generation of knowledge tailored to clinical practice, and
      knowledge sharing. The nature, philosophical basis, roles of research staff
      members, outputs and impacts, and strengths and limitations of each model are
      described, in the context of a long-standing, interdisciplinary research program
      in a children's rehabilitation service organization. The use of the model
      framework as a tool for the design of interdisciplinary, community-based research
      programs is discussed.

PMID- 18336907
TI  - The liberal state and mental health.

PMID- 18336908
TI  - Genome-wide analysis displays marked induction of EBI3/IL-27B in IL-18-activated
      AML-derived KG1 cells: critical role of two kappaB binding sites in the human
      EBI3 promotor.
AB  - The cell line KG1 is derived from a patient with acute myeloid leukemia.
      Activation of KG1 cells by interleukin (IL)-18 is associated with induction of
      key Th1 signature parameters such as T-bet and interferon-gamma. Here we set out
      to characterize the genome-wide mRNA expression profile under the condition of
      short-term stimulation (4h) with IL-18 using the Affymetrix GeneChip((R)) Array
      System. Besides the chemokines CXCL10, CXCL11, and CCL1 we identified Epstein
      Barr virus induced gene-3 (EBI3)/IL-27B as being among those genes that are
      profoundly upregulated by IL-18 in KG1 cells. Thorough investigation revealed
      that IL-18-induced EBI3 mRNA efficiently translates into protein. Electromobility
      shift analysis and mutational analysis of the human EBI3 promoter identified two
      nuclear factor-kappaB binding sites as being crucial for induction by pro
      inflammatory cytokines like IL-18. In addition, we demonstrate that KG1 cells
      express the Type A IL-27 receptor chain (WSX-1) and display STAT-1, -3 activation
      as well as induction of SOCS-3 under the influence of IL-27. IL-18 shows
      therapeutic potential in murine leukemia and is currently being evaluated in
      phase II clinical trials for the treatment of immunologically sensitive cancers.
      Since IL-27 mediates anti-cancer bioactivity in animal models, data presented
      herein may add a novel facet to tumorsuppressive characteristics of IL-18.

PMID- 18336909
TI  - Vasoactive intestinal peptide suppresses toll-like receptor 4 expression in
      macrophages via Akt1 reducing their responsiveness to lipopolysaccharide.
AB  - Toll-like receptor 4 (TLR4) recognizes and initiates signals from Gram-negative
      bacterial lipopolysaccharide (LPS) triggering the inflammatory response.
      Expression levels of TLR4 on macrophages partly regulate the magnitude of the
      response to LPS. Vasoactive Intestinal Peptide (VIP) is known to block
      inflammatory responses by inhibiting pro-inflammatory cytokine production from
      activated macrophages. In the present report we demonstrate that VIP directly
      suppressed TLR4 expression on naive primary mouse macrophages utilizing
      signalling cascades that control TLR4 transcription. VIP-induced suppression of
      TLR4 occurred at the transcriptional level by decreasing PU.1 DNA binding.
      Mutation of the proximal PU.1 but not the AP-1-binding site on the TLR4 promoter
      abrogated VIP-induced suppression of TLR4 transcription. Moreover, inhibition of
      PI3K by wortmannin or homologous deletion of the Akt1 isoform, a pathway known to
      act as a negative regulator of macrophage activation, alleviated the suppressive
      action of VIP on TLR4 expression. To evaluate the biological significance of VIP
      effect on TLR4 expression, Raw264.7 macrophages were pre-treated with VIP for 24h
      and then exposed to LPS. Pre-treatment with VIP rendered macrophages hypo
      responsive to LPS resulting in reduced pro-inflammatory cytokine production.
      Moreover, in vivo administration of VIP in C57BL/6 mice resulted in lower IL-6
      production upon treatment with LPS. Overall, the results indicate that VIP
      promotes endotoxin tolerance by downregulating TLR4 expression via Akt1.

PMID- 18336910
TI  - Genetic deficiency of complement factor H in a patient with age-related macular
      degeneration and membranoproliferative glomerulonephritis.
AB  - Age-related macular degeneration (AMD) and membranoproliferative
      glomerulonephritis type II (MPGN2) are dense deposit diseases that share a
      genetic association with complement genes and have complement proteins as
      important components of the dense deposits. Here, we present the case of a 64
      year-old smoker male who developed both AMD and MPGN2 in his late 50s. The
      patient presented persistent low plasma levels of C3, factor H levels in the
      lower part of the normal range and C3NeF traces. Genetic analyses of the CFH,
      CFB, C3, CFHR1-CFHR3 and LOC387715/HTRA1 genes revealed that the patient was
      heterozygote for a novel missense mutation in exon 9 of CFH (c.1292 G>A) that
      results in a Cys431Tyr substitution in SCR7 of the factor H protein. In addition,
      he was homozygote for the His402 CFH allele, heterozygote for the Ser69 LOC387715
      allele, homozygote for the Arg32 (BFS) CFB allele, heterozygote for the Gly102
      (C3F) C3 allele and carried no deletion of the CFHR1/CFHR3 genes. Proteomic and
      functional analyses indicate absence in plasma of the factor H allele carrying
      the Cys431Tyr mutation. As a whole, these data recapitulate a prototypical
      complement genetic profile, including a partial factor H deficiency and the
      presence of major risk factors for AMD and MPGN2, which support the hypothesis
      that these dense deposit diseases have a common pathogenic mechanism involving
      dysregulation of the alternative pathway of complement activation.

PMID- 18336911
TI  - Transcriptional silencing of RFXAP in MHC class II-deficiency.
AB  - MHC-II deficiency is recognized by defects in components of the RFX complex or
      CIITA. In this study, we have characterized at the molecular level the putative
      defect in MHC-II regulatory factors of a recently identified MHC-II deficiency
      patient (FGK). We found that this patient lacked detectable levels of mRNA and
      protein of the RFX complex subunit RFXAP. It was subsequently established that
      the RFXAP gene in FGK differed from wild type RFXAP by a homozygous 75bp
      insertion in the 5'-UTR, which impaired the activity of the FGK RFXAP promoter.
      The transcriptional silent state of RFXAP correlated with reduced recruitment of
      RNA polymerase II to FGK RFXAP chromatin. Together, this insertion in the
      promoter region represents a novel type of MHC-II gene silencing in MHC-II
      deficiency patients.

PMID- 18336913
TI  - Theoretical insight into the hydroxylamine oxidoreductase mechanism.
AB  - The multiheme enzyme hydroxylamine oxidoreductase from the autotrophic bacteria
      Nitrosomonas europaea catalyzes the conversion of hydroxylamine to nitrite, with
      a complicate arrangement of heme groups in three subunits. As a distinctive
      feature, the protein has a covalent linkage between a tyrosyl residue of one
      subunit and a meso carbon atom of the heme active site of another. We studied the
      influence of this bond in the catalysis from a theoretical perspective through
      electronic structure calculations at the density functional theory level,
      starting from the crystal structure of the protein. Geometry optimizations of
      proposed reaction intermediates were used to calculate the dissociation energy of
      different nitrogen containing ligands, considering the presence and absence of
      the meso tyrosyl residue. The results indicate that the tyrosine residue enhances
      the binding of hydroxylamine, and increases the stability of a Fe(III)NO
      intermediate, while behaving indifferently in the Fe(II)NO form. The calculations
      performed on model systems including neighboring aminoacids revealed the probable
      formation of a bidentate hydrogen bond between the Fe(III)H(2)O complex and Asp
      257, in a high-spin aquo complex as the resting state. Characterization of non
      planar heme distortions showed that the meso-substituent induces significant
      ruffling in the evaluated intermediates.

PMID- 18336912
TI  - Porcine reproductive and respiratory syndrome virus (PRRSV) suppresses interferon
      beta production by interfering with the RIG-I signaling pathway.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is the cause of an
      economically important swine disease that has been devastating the swine industry
      since the late 1980s. Accumulating evidences have revealed that PRRSV infection
      fails to induce type I interferon (IFN-alpha/beta), which are normally induced
      rapidly during virus replication in virus-infected cells. However, the potential
      mechanisms remain largely unclear. In this study, we showed that PRRSV infection
      activated the signal transduction components of NF-kappaB and AP-1, but not of
      interferon regulatory factor 3 (IRF3), an essential IFN-beta transcription
      factor. Furthermore, PRRSV infection significantly blocked synthetic dsRNA
      induced IFN-beta production and IRF3 nuclear translocation. To better understand
      the upstream signaling events that suppress IRF3 activation, we further
      investigated the roles of individual components of the retinoic acid-inducible
      gene I (RIG-I)- and Toll-like receptor 3 (TLR3)-mediated signaling pathway for
      IFN-beta production during PRRSV infection. We observed that PRRSV infection
      significantly inhibited dsRNA-induced IRF3 activation and IFN-beta generation by
      inactivating IFN-beta promoter stimulator 1 (IPS-1), an adaptor molecule of RIG
      I. In contrast, PRRSV infection only partially reduced the activation of TIR
      domain-containing adaptor inducing IFN-beta (TRIF), an adaptor molecule of TLR3.
      Our results suggest that PRRSV infection suppresses production of IFN-beta
      primarily by interfering with the IPS-1 activation in the RIG-I signaling
      pathway.

PMID- 18336914
TI  - Modeling tyrosinase activity. Effect of ligand topology on aromatic ring
      hydroxylation: an overview.
AB  - Synthetic modeling of tyrosinase (o-phenol ring hydroxylation) has emerged as a
      novel class of successful biomimetic studies. It is a well-established fact that
      the reaction of dioxygen with copper(I) complexes of m-xylyl-based ligands
      generate putative copper-oxygen intermediate species such as side-on peroxo
      {CuII2(mu-O2)}2+ [in some cases bis-oxo {CuIII2(mu-O)2}2+ in equilibrium with
      isomeric side-on peroxo], due to oxygen activation. Electrophilic attack of such
      species brings about monooxygenase activity by incorporating one of the oxygens
      to m-xylyl ring of the ligand and the other oxygen is reduced to hydroxide ion.
      The goal of this review is to provide a concise overview of the present day
      knowledge in this field of research to emphasize the important role the designed
      ligands play in eliciting the desired tyrosinase-like chemistry.

PMID- 18336915
TI  - Total joint replacement in HIV positive patients.
AB  - BACKGROUND: Recent HIV therapies have improved life expectancy in HIV positive
      patients. For the purpose of the following retrospective investigation, we
      analyzed the results of total joint replacement in HIV positive patients. This
      study exemplifies orthopaedic treatment options and perioperative problems in HIV
      positive patients. Our population included a high proportion of hemophilic
      patients. DESIGN AND METHODS: Between 1988 and 2000, we performed 55
      endoprosthetic procedures (20 total hip replacements (THR), 33 total knee
      replacements (TKR), two shoulder replacements) in 41 patients suffering form HIV.
      Thirty patients are afflicted with hemophilia, seven patients were intravenous
      drug addicts. The mean follow-up was 81 months (2-14) years. Patients were seen
      annually; either the Harris Hip Score or the Knee Society Rating System was
      applied. RESULTS: The following septic complications were observed: a mycotic
      abscess of both hips 5/10 months after bilateral THR, two early infections
      following coxitis in patients with intravenous drug abuse, and one further case
      of septic loosening after 15 months in one patient after THR. Furthermore, one
      aseptic loosening of a THR after 14 months in a hemophilic patient was seen.
      After TKR, two early infections in patients with intravenous drug addiction were
      seen. The total complication rate was 12.7%. A coherency between the infection
      rate and the CD4+ count was not seen. DISCUSSION: An analysis of the results
      shows that the complications occurred in patients living under difficult social
      circumstances. Whereas total joint replacement in hemophilic patients with or
      without HIV seems to be a fairly safe procedure concerning the postoperative
      infection rate, intravenous drug abuse increases the risk. Functional outcome
      does not differ from an HIV negative population both in the TKR and THR groups.

PMID- 18336916
TI  - Propionibacterium acnes is a common colonizer of intravascular catheters.
AB  - Propionibacterium spp. are common flora of human skin. Nevertheless, currently
      recommended culture procedures do not include anaerobic processing with the
      result that this organism may go undetected on a colonized catheter. To determine
      the rate of catheter colonization by Propionibacterium spp., a sample of 1000
      vascular catheters was processed by the roll-plate technique and, after
      conventional aerobic processing, all primary culture plates were reincubated in
      an anaerobic atmosphere. Propionibacterium acnes was detected in significant
      counts in the vascular catheters of 39 patients. This represents 14.7% (95% CI,
      12.5-16.9) of all positive catheters. Propionibacterium is the second most
      frequent genus-colonizing catheter tips after Staphylococcus spp. Methodological
      shortcomings impair the detection and proper adscription of P. acnes as a
      potential cause of catheter-related infections.

PMID- 18336917
TI  - Racial differences in cervical cytokine concentrations between pregnant women
      with and without bacterial vaginosis.
AB  - We have examined the association between cervical cytokine, chemokine and growth
      factor concentrations with bacterial vaginosis (BV) in pregnant white and black
      women. A nested case-control analysis was performed to examine 28 cervical
      cytokine, chemokine and growth factor concentrations in 83 white women (55 with
      normal flora and 28 with BV) and 81 black women (39 with normal flora and 42 with
      BV). White women with BV had significantly lower IP10 (P=0.001) and MCP1
      (P=0.006) concentrations compared to women with normal flora. Black women with BV
      had higher IL-1alpha (P<0.001) concentrations than those with normal flora. In
      women with normal flora, whites had significantly higher levels of IL-1alpha
      (P=0.047), IL-6 (P=0.010), IL-10 (P=0.016) and PDGF-BB (P=0.010) than blacks.
      There were no significant concentration differences between white and black women
      with BV. These results demonstrate significant differences in cytokine and
      chemokine concentrations between women with and without BV. Ethnic differences in
      cytokine concentrations were also observed in women with normal flora, indicating
      that white and black women with normal flora have different cytokine levels, but
      respond to BV in a similar manner.

PMID- 18336918
TI  - Impact of concurrent naturalistic pharmacotherapy on psychotherapy of complicated
      grief.
AB  - Complicated grief (CG) is a debilitating syndrome that can be reliably
      identified, but there is a paucity of research examining treatment of CG. A
      targeted psychotherapy for complicated grief (CGT) was recently shown to be
      efficacious [Shear, K., Frank, E., Houck, P.R., Reynolds, C.F., 3rd, 2005.
      Treatment of complicated grief: a randomized controlled trial. Journal of the
      American Medical Association 293, 2601-2608]. We provide a detailed examination
      of the association of naturalistic pharmacotherapy use with treatment response
      and study completion in the psychotherapy study. Patients on an antidepressant
      medication were more likely to complete a full course of CGT (91% vs. 58%
      completed), while antidepressant use had no effect on completion rates for the
      comparator, interpersonal psychotherapy (70% vs. 77%). Our naturalistic data
      underscore the need for prospective, randomized controlled studies of CG
      pharmacotherapy and psychotherapy alone and in combination.

PMID- 18336919
TI  - Treatment of post-traumatic stress disorder with eye movement desensitization and
      reprocessing: outcome is stable in 35-month follow-up.
AB  - Post-traumatic stress disorder (PTSD) is an anxiety disorder that may follow
      major psychological trauma. The disorder is longstanding, even chronic, and there
      is a need for effective treatment. The most effective short-term treatments are
      cognitive behavioural therapy and eye movement desensitization and reprocessing
      (EMDR). Twenty subjects with chronic PTSD following occupational health hazards
      from "person under train" accidents or assault at work were treated with five
      sessions of EMDR. They were assessed with psychometric scales and diagnostic
      interviews before treatment, directly after treatment, at 8 months, and at 35
      months after the end of Therapy. The primary outcome variable was full diagnosis
      of PTSD according to the DSM-IV diagnostic criteria. Results from interview-based
      and self-evaluation psychometric scales were used as secondary outcome variables.
      Immediately following treatment, the patients were divided up into two groups,
      initial remitters (12 of 20) and non-remitters (8 of 20). There were no drop-outs
      during therapy, but three patients withdrew during follow-up. The initial result
      was maintained at the 35-month follow-up. The secondary outcome variables also
      showed a significant immediate change towards normality that was stable during
      the long-term follow-up. After 3 years of follow-up, 83% of the initial remitters
      had full working capacity.

PMID- 18336920
TI  - Infection with prevalent clinical strains of Mycobacterium tuberculosis leads to
      differential maturation of monocyte derived dendritic cells.
AB  - The link between innate and adaptive host immune response to Mycobacterium
      tuberculosis (M.tb) is driven by dendritic cells (DC). In this study, we examined
      the ability of prevalent clinical strains from south India (S7, S10) and
      laboratory strain H37Rv (Rv) to induce maturation of monocyte derived dendritic
      cells (MoDC). The phenotypic and functional changes of DC upon infection with
      different strains of M.tb were evaluated. It was observed that S7 and Rv strains
      partially hampered the maturation of MoDC as reflected by the low expression of
      maturation markers and co-stimulatory markers when compared to LPS stimulated
      MoDC. In contrast, strain S10 infected DC showed a marked increase in the
      expression of these markers. The functional property was investigated by the
      ability of infected MoDC to induce T-cell proliferation and to stimulate
      secretion of IFN-gamma by CD4(+)T-cells. It was found that Rv and S7 infected
      MoDC were less efficient in inducing T-cell proliferation. The secretion of IL-12
      by Rv and S7 infected MoDC was also found to be significantly lesser than LPS
      stimulated MoDC. On the other hand, S10 infected MoDC showed enhanced T-cell
      stimulation and cytokine secretion. Together these results indicate that there is
      a substantial variability in the capacity of M.tb clinical strains to induce
      maturation of DC which may be dependent upon their virulence.

PMID- 18336921
TI  - Which children would benefit most from tympanostomy tubes (grommets)? A personal
      evidence-based review.
AB  - Otitis media with effusion (OME) is a common condition in young children. OME
      causes some hearing loss, and can cause permanent changes in the tympanic
      membrane as well as other symptoms. In most cases OME is of short duration. As
      long-lasting bilateral OME for decades has been associated with delayed cognitive
      and language development, parents and ENT specialists have a positive attitude
      towards treatment with tympanostomy tubes (TT). METHOD: This personal evidence
      based review is build on own observations and research combined with newer
      studies and guidelines. RESULTS: The review argues for a relatively restrictive
      treatment policy concerning the use of TT in children with OME without signs or
      symptoms of impaired social or linguistic function. CONCLUSION: Six months with
      bilateral OME and significant hearing loss should be present before treatment
      with TT in otherwise healthy children. At the moment we have no evidence for the
      subgroups of children excluded from the RCTs, i.e. children with speech/language
      delays, behaviour and learning problems, or syndromes. Clinicians will need to
      make their own decisions regarding treatment of such children. The situation just
      now is that some children are over-treated and some are under-treated. There is
      an urgent need for prospective cohort studies and randomised studies on children
      with long-lasting OME in an attempt to characterise the children who would
      benefit most from TT.

PMID- 18336922
TI  - Otological findings among Nigerian children with sickle cell anaemia.
AB  - BACKGROUND/AIM: Various degrees of hearing loss have been associated with sickle
      cell anaemia, especially of the sensorineural type (SNHL). However, there is
      little information on hearing pattern among sickle cell children in Nigeria. This
      study is to determine the prevalence of sensorineural hearing loss (SNHL) among
      children with sickle cell anaemia (SCA). PATIENTS AND METHODS: Eighty (80) stable
      children aged 4-15 with Hbss attending the pediatric sickle cell clinic and also
      60 control patients with HbAA, matched for age, sex at the pediatric general
      medical clinic of the University of Ilorin teaching hospital, Ilorin, Nigeria,
      all had prospective study of their pure tone audiological assessment (PTA) and
      tympanometric evaluations done over a year period. RESULTS: Their age range was 4
      15 years with a mean of 9.4 for the Hbss and 9.7 for the control group. The
      male/female ratio was 1.3:1 and 1.5:1 for SCA and control subjects respectively.
      25 subjects (50 ears) had abnormal audiograms among the SCA subjects and OME was
      the cause in 22 subjects and only three (3) had mild SNHL which was bilateral.
      However, in the control group 15 had abnormal audiograms and all were due to OME
      and none had SNHL. OME was bilateral in 19 subjects with SCA, two on the left and
      only one on the right. In the control group, 11 of the OME was bilateral and only
      four were on the left side. The prevalence of SNHL was 3.8% and OME was 27.5%.
      CONCLUSION: We have found a prevalence rate for SNHL of 3.8% for 80 subjects with
      HbSS, and all cases have been a mild bilateral high frequency SNHL. Our findings
      suggested that SNHL is uncommon in early childhood, specifically during the years
      of language acquisition and early schooling. This could mean an age dependant
      prevalence rate of SNHL among SCA patients. However, no difference in the
      incidence of OME among both groups which can lead to educational difficulties
      from the resultant speech and language defects.

PMID- 18336923
TI  - Direct recovery of infectious pestivirus from a full-length RT-PCR amplicon.
AB  - This study describes the use of a novel and rapid long reverse transcription (RT)
      PCR for the generation of infectious full-length cDNA of pestiviruses. To produce
      rescued viruses, full-length RT-PCR amplicons of 12.3 kb, including a T7
      promotor, were transcribed directly in vitro, and the resulting RNA transcripts
      were electroporated into ovine cells. Infectious virus was obtained after one
      cell culture passage. The rescued viruses had a phenotype similar to the parental
      Border Disease virus strain. Therefore, direct generation of infectious
      pestiviruses from full-length RT-PCR cDNA products could be a valuable instrument
      for virus rescue, conservation and further characterization.

PMID- 18336924
TI  - Generation of internal image monoclonal anti-idiotypic antibodies against
      idiotypic antibodies to GP5 antigen of porcine reproductive and respiratory
      syndrome virus.
AB  - Syngeneic monoclonal anti-idiotypic antibodies (Mab2s) were generated against
      idiotypic antibodies to membrane glycoprotein GP5 of porcine reproductive and
      respiratory syndrome virus (PRRSV) using the sequential immunization method. Six
      of 12 Mab2s possessed potential internal image characteristics by recognizing a
      common idiotype on murine and swine anti-GP5 antibodies. Further serological
      characterization demonstrated that one of the Mab2 (Mab2-5G2) represents internal
      image anti-idiotope which mimicked the GP5 antigen that inhibited the interaction
      between idiotypic anti-GP5 antibodies and GP5 antigen, its reaction with the
      idiotypic anti-GP5 antibody was inhibited by GP5 antigen and detected the common
      Id on anti-PRRSV antibodies from pigs that were experimentally infected with
      PRRSV. In addition, Mab2-5G2 identified a soluble protein on MA-104 and porcine
      alveolar macrophages. These results indicate that Mab2-5G2 may be a useful
      candidate as an alternative PRRSV serodiagnostic reagent and a useful probe to
      study PRRSV-cell interaction.

PMID- 18336925
TI  - Genotypic detection of acyclovir-resistant HSV-1: characterization of 67 ACV
      sensitive and 14 ACV-resistant viruses.
AB  - Infections due to herpes simplex virus (HSV) resistant to acyclovir (ACV)
      represent an important clinical concern in immunocompromised patients. In order
      to switch promptly to an appropriate treatment, rapid viral susceptibility assays
      are required. We developed herein a genotyping analysis focusing on thymidine
      kinase gene (TK) mutations in order to detect acyclovir-resistant HSV in clinical
      specimens. A total of 85 HSV-1 positive specimens collected from 69 patients were
      analyzed. TK gene could be sequenced directly for 81 clinical specimens (95%) and
      68 HSV-1 specimens could be characterized as sensitive or resistant by genotyping
      (84%). Genetic characterization of 67 susceptible HSV-1 specimens revealed 10
      polymorphisms never previously described. Genetic characterization of 14
      resistant HSV-1 revealed 12 HSV-1 with either TK gene additions/deletions (8
      strains) or substitutions (4 strains) and 2 HSV-1 with no mutation in the TK
      gene. DNA polymerase gene was afterwards explored. With this rapid PCR-based
      assay, ACV-resistant HSV could be detected directly in clinical specimens within
      24 h.

PMID- 18336926
TI  - Effect of oral treatment with (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA on
      replication of murine cytomegalovirus (MCMV) or human cytomegalovirus (HCMV) in
      animal models.
AB  - We utilized BALB/c mice infected with murine CMV (MCMV) or severe combined
      immunodeficient (SCID) mice implanted with human fetal tissue and infected with
      HCMV to determine the efficacy of (S)-9-[3-hydroxy-2
      (phophonomethoxy)propyl]adenine ((S)-HPMPA), hexadecyloxypropyl-(S)-HPMPA (HDP
      (S)-HPMPA) or octadecyloxyethyl-(S)-HPMPA (ODE-(S)-HPMPA). In MCMV-infected
      BALB/c mice, oral HDP-(S)-HPMPA at 30 mg/kg significantly reduced mortality when
      started 24-48 h post inoculation. In the experimental HCMV infection, oral
      administration of vehicle or 10mg/kg of (S)-HPMPA, HDP-(S)-HPMPA or ODE-(S)-HPMPA
      was initiated 24h after infection and continued for 28 consecutive days.
      Cidofovir (CDV), at 20mg/kg given i.p., was used as a positive control. HDP-(S)
      HPMPA or ODE-(S)-HPMPA significantly reduced viral replication compared to
      vehicle-treated mice, while oral (S)-HPMPA was ineffective.

PMID- 18336927
TI  - Treatment of Marburg and Ebola hemorrhagic fevers: a strategy for testing new
      drugs and vaccines under outbreak conditions.
AB  - The filoviruses, Marburg and Ebola, have the dubious distinction of being
      associated with some of the highest case-fatality rates of any known infectious
      disease--approaching 90% in many outbreaks. In recent years, laboratory research
      on the filoviruses has produced treatments and vaccines that are effective in
      laboratory animals and that could potentially drastically reduce case-fatality
      rates and curtail outbreaks in humans. However, there are significant challenges
      in clinical testing of these products and eventual delivery to populations in
      need. Most cases of filovirus infection are recognized only in the setting of
      large outbreaks, often in the most remote and resource-poor areas of sub-Saharan
      Africa, with little infrastructure and few personnel experienced in clinical
      research. Significant political, legal, and socio-cultural barriers also exist.
      Here, we review the present research priorities and environment for field study
      of the filovirus hemorrhagic fevers and outline a strategy for future prospective
      clinical research on treatment and vaccine prevention.

PMID- 18336928
TI  - Facilitation of avoidance behaviour in mice chronically treated with heroin or
      methadone.
AB  - Although the repercussion of chronic treatment with large amounts of opioids on
      cognitive performance is a matter of concern, the effects of opioid drugs on
      passive avoidance learning have been scarcely studied. Here, we analyzed the
      effects of prolonged administration of heroin and methadone, as well as the
      impact of suffering repeated episodes of withdrawal on fear-motivated learning
      using the passive avoidance test. Mice received chronic treatment (39 days) with
      methadone (10 mg/kg/24 h), associated or not with repeated withdrawal episodes,
      or with heroin (5 mg/kg/12 h). Our results show that, regardless of the type of
      treatment received, all mice displayed similar basal thermal nociceptive
      thresholds during 25 days of treatment. In the hot plate test, both methadone and
      heroin induced antinociception 30 min after drug administration. The analgesic
      effect was absent when measured 4 h after heroin and 12 h after methadone. Pain
      behavioural responses elicited by growing intensities of electric shock, applied
      on day 28th of treatment, were similar in all groups of mice. Our results
      indicate that chronic opioid treatment had promnesic effects on passive avoidance
      behaviour in mice, unrelated to changes in the nociceptive state.

PMID- 18336929
TI  - Effect of insulin and melatonin on acetylcholinesterase activity in the brain of
      amnesic mice.
AB  - Basal forebrain cholinergic neurons and oxidative stress in brain have been
      suggested to play an important role in the regulation of memory functions.
      Therefore, the present study was planned to study the effect of donepezil, an
      anticholinesterase antidementia drug, insulin and melatonin, an antioxidant, on
      memory deficit and acetylcholinesterase (AChE) activity in brain areas of
      scopolamine-induced amnesic mice. Memory was tested by passive avoidance (PA)
      test in Swiss adult male mice. A significant increase in transfer latency time
      (TLT) in 2nd trial as compared to 1st trial is considered as successful learning.
      Scopolamine (3 mg/kg i.p.) was administered 5 min prior to 1st trial to induce
      amnesia. AChE activity in detergent soluble (DS) and salt soluble (SS) fractions
      was estimated in brain areas after completion of 2nd trial. Scopolamine was
      effective in producing memory impairment (amnesia) which was reverted by
      donepezil (5 mg/kg p.o.), insulin (1 IU/kg i.p.) and melatonin (20 mg/kg p.o.).
      AChE activity in DS fraction of scopolamine amnesic mice was inhibited by
      donepezil, insulin and melatonin with varying extent in different brain regions,
      whereas AChE activity in SS fraction was not much affected. The results
      demonstrate that anti-amnesic effect of donepezil, insulin and melatonin may be
      mediated through enhancement of cholinergic activity.

PMID- 18336930
TI  - Early signs of neurolipidosis-related behavioural alterations in a murine model
      of metachromatic leukodystrophy.
AB  - Arylsulfatase A (ASA)-deficient mice represent an animal model for the lysosomal
      storage disorder metachromatic leukodystrophy (MLD). Although the model has been
      applied in pathophysiological and therapeutic studies, the behavioural phenotype
      of ASA(-/-) mice is only partially characterized, and the most decisive outcome
      measures for therapy evaluation only emerge beyond 1 year of age. Presently, ASA(
      /-) mice and ASA(+/-) control mice were studied at 6 and 12 months of age on an
      extensive battery including tests of neuromotor ability, exploratory behaviour,
      and learning and memory. Overt signs of ataxia were not observed in 6-month-old
      ASA(-/-) mice, but quantitative gait analysis during open-field exploration
      revealed that ASA(-/-) mice displayed increased hind base width and increased
      stride lengths for all paws. Their covert motor incoordination was evident in a
      correlation analysis which unveiled decreased harmonisation of concurrent gait
      parameters. For example, while ASA(+/-) controls demonstrated substantial
      convergence of front and hind base width (r=0.54), these variables actually
      diverged in ASA(-/-) mice (r=-0.37). Furthermore, various behavioural
      observations indicated emotional alterations in ASA(-/-) mice. Six-month-old ASA(
      /-) mice also showed decreased response rates in scheduled operant responding.
      The present findings could provide relevant behavioural outcome measures for
      further use of this murine MLD model in preclinical studies.

PMID- 18336931
TI  - Reproductive and stress hormone levels in goldfish (Carassius auratus) exposed to
      oil sands process-affected water.
AB  - Athabasca oil sands mining in northern Alberta produces process-affected waters
      that are characterized by the presence of naphthenic acids, polycyclic aromatic
      hydrocarbons, and high salinity. The purpose of this study was to examine the
      impact of these process-affected waters on reproductive and stress related
      endpoints in mature goldfish, Carassius auratus. In two separate studies,
      testosterone and 17beta-estradiol levels in the plasma were significantly reduced
      in both male and female goldfish caged for 19 days in process-affected waters
      relative to controls. This effect was most pronounced in goldfish caged at a site
      containing mature fine tailing and tailings pond water (P5). Ovarian and
      testicular tissues from fish in the caging studies were incubated in vitro to
      evaluate potential differences in basal steroid production levels and
      responsiveness to human chorionic gonadotropin (hCG). Basal levels of
      testosterone were reduced significantly in males and females from P5 compared
      with the control pond (P1) demonstrating that the gonads from exposed fish had a
      diminished steroidogenic capacity. Gonadal tissues of fish from all ponds
      responded similarly to hCG suggesting that the steroid biosynthetic pathway
      remained functionally intact. Plasma cortisol levels were significantly higher in
      male goldfish caged in a pond containing mature fine tailings and capped with
      uncontaminated water (P3) and in P5 compared with P1. Collectively, these studies
      suggest that waste products of oil sands mining have the potential to disrupt the
      normal endocrine functioning in exposed fish through alterations to both
      reproductive and glucocorticoid hormone biosynthesis. In additional laboratory
      studies, exposure of goldfish to a naphthenic acid extract for 7 days failed to
      replicate the effects of processes-affected waters on plasma steroid levels and
      the causative agent(s) responsible for the effects on steroid biosynthesis
      remains to be identified.

PMID- 18336932
TI  - Caregiving for elder relatives: which caregivers experience personal
      benefits/gains?
AB  - The present study asks whether the positive, rewarding experiences of caregiving
      (benefits/gains) emerge merely as a function of caregiver personality, or
      whether, after personality traits (agreeableness, conscientiousness,
      extroversion, neuroticism) are taken into account, other interpersonal factors
      make a difference. Survey data were collected from 63 family caregivers.
      Bivariate analyses revealed that caregiving benefits/gains were significantly and
      positively associated with two personality traits (agreeableness, extroversion),
      family and spouse/partner socio-emotional support, and prior relationship
      quality. Hierarchical regressions indicated that whereas neither family socio
      emotional support nor prior relationship quality significantly predicted variance
      in caregiving benefits/gains beyond that accounted for by agreeableness and
      extroversion, spouse/partner socio-emotional support did. Implications for
      research and practice are discussed.

PMID- 18336933
TI  - Predictors of treatment failures during chemotherapy: A prospective study on 110
      older cancer patients.
AB  - Several instruments have been proposed to improve treatment decisions in elderly
      cancer patients, but evidence of their impact in clinical practice is limited.
      The aim of this study was to analyze the role of clinical and functional factors
      in predicting serious adverse events, including death, severe toxicity or
      treatment interruption, during chemotherapy in elderly cancer patients. The
      survey evaluated elderly with lung or colon or breast cancer treated with
      chemotherapy, followed by S. Giovanni Battista Hospital. We enrolled 110
      consecutive patients older than 70 years of age with lung (n=45), colon (n=50)
      and breast (n=15) cancer between October 2004 and October 2005. Overall, 73/110
      patients (66.4%) experienced adverse events as death (n=14), grades III and IV
      toxicity (n=40), or treatment interruption for other reasons (n=19). The
      variables with stronger predictivity were advanced stage, toxicity of treatment,
      level of comorbidity and Karnofsky performance status (KPS). instrumental
      activities of daily living (IADL) index and age itself were not independent
      predictors. In conclusion our results confirm the need of a careful selection of
      elderly patients suitable for chemotherapy, giving more weight to comorbidity and
      KPS scores than to age itself. The potential role of other functional evaluations
      need to be further assessed in randomized controlled trials.

PMID- 18336934
TI  - Anthropometric traits and aging: a cross-sectional survey in diabetic elderly
      women.
AB  - The aim of this cross-sectional study was to identify the peculiar anthropometric
      changes in elderly diabetic women aged 70 years and above. The subjects were 91
      women suffering from type-2 diabetes and 101 healthy female controls; all these
      192 North-Italian women were aged 70 years or over. Eight anthropometric
      measurements were collected for each subject. We observed significant
      anthropometric differences between diabetic women and controls. The changes with
      aging were more evident in women suffering from type-2 diabetes than in controls
      of the same age groups. In conclusion, the diabetic women are more in overweight
      than the controls. Moreover, diabetes resulted associated with an accelerated
      process of aging in anthropometric traits.

PMID- 18336935
TI  - Rescue extracorporeal circulation as bridge to recovery in fulminant cocaine
      induced heart failure.
AB  - Cocaine is an increasing cause of admission in the emergency room. The widespread
      abuse of this drug during the last decade in the USA is now widely emerging in
      Europe. Because of its various cardio-vascular complications, cocaine is one of
      the most death-related drugs known at this time. The following report describes
      the dramatic case of a young man polydrug addict presenting at our institution
      with life-threatening acute heart failure that developed shortly after his very
      first cocaine intake. Because of the lack of response to intensive medical
      treatment, we decided to perform a percutaneous extracorporeal circulation
      membranous oxygenation (ECMO) that allowed survival and rapid left ventricular
      function recovery. This report highlights cocaine as a rising trigger of acute
      heart failure in young people and is, to the best of our knowledge, the first
      report that illustrates ECMO as an effective hemodynamic support in the course of
      fulminant cocaine-induced cardiomyopathy.

PMID- 18336936
TI  - Evaluation of test-strategies for estimating probability of low prevalence of
      paratuberculosis in Danish dairy herds.
AB  - Paratuberculosis is a chronic infection affecting cattle and other ruminants. In
      the dairy industry, losses due to paratuberculosis can be substantial in infected
      herds and several countries have implemented national programmes based on herd
      classification to manage the disease. The aim of this study was to develop a
      method to estimate the probability of low within-herd prevalence of
      paratuberculosis for Danish dairy herds. A stochastic simulation model was
      developed using the R programming environment. Features of this model included:
      use of age-specific estimates of test-sensitivity and specificity; use of a
      distribution of observed values (rather than a fixed, low value) for design
      prevalence; and estimates of the probability of low prevalence (PrLow) based on a
      specific number of test-positive animals, rather than for a result less than or
      equal to a specified cut-point number of reactors. Using this model, five herd
      testing strategies were evaluated: (1) milk-ELISA on all lactating cows; (2) milk
      ELISA on lactating cows<or=4 years old; (3) milk-ELISA on lactating cows>4 years
      old; (4) faecal culture on all lactating cows; and (5) milk-ELISA plus faecal
      culture in series on all lactating cows. The five testing strategies were
      evaluated using observed milk-ELISA results from 19 Danish dairy herds as well as
      for simulated results from the same herds assuming that they were uninfected.
      Whole-herd milk-ELISA was the preferred strategy, and considered the most cost
      effective strategy of the five alternatives. The five strategies were all
      efficient in detecting infection, i.e. estimating a low PrLow in infected herds,
      however, PrLow estimates for milk-ELISA on age-cohorts were too low in simulated
      uninfected herds and the strategies involving faecal culture were too expensive
      to be of practical interest. For simulated uninfected herds, whole-herd milk
      ELISA resulted in median PrLow values>0.9 for most herds, depending on herd size
      and age-structure. None of the strategies provided enough power to establish a
      high PrLow in smaller herds, or herds with a younger age-structure. Despite this,
      it appears as if the method is a useful approach for herd-classification for most
      herds in the Danish dairy industry.

PMID- 18336937
TI  - Flock-level case-control study of slaughter-lamb pneumonia in New Zealand.
AB  - Subclinical pneumonia is common in production lambs, and causes reductions in
      growth rate. We selected farms from meat-inspection records of three New Zealand
      abattoirs from December 2000 to May 2001 to study risk factors for flocks having
      >or=3% of their lambs with >or=10% of the lung surface with lesions, compared to
      flocks with a zero lamb-level prevalence of such pneumonia. A questionnaire of
      management practices was mailed to participating managers of case and control
      farms and we received responses from 132/192 (69%) cases and 181/300 (60%) in
      control farms. Risk factors for case farms were shearing lambs on the day of
      weaning (OR 6.4), breeding ewe replacements on-farm (OR 4.0), and the percentage
      of lambs sold between March and May (OR 1.0 for <23% sold (reference category),
      OR 3.9 for 23-42% sold, OR 2.7 for 43-64% sold, OR 4.3 for >64% sold). Protective
      factors included: grazing lambs at a fixed stocking rate after weaning (OR 0.4),
      injecting lambs with vitamin B12 at the time of docking (OR 0.4), and at the time
      of weaning (OR 0.3). Path analysis was used to show important associations
      between risk and protective factors differentiated according to time (e.g. before
      and after birth, at weaning and during growth on pasture). Flocks breeding their
      own ewe replacements were more likely to shear lambs at weaning, were less likely
      to buy lambs post-weaning and more likely to have ill-thrift present in >5% of
      lambs post-weaning. The purchase of lambs post-weaning was indirectly associated
      with greater odds of pneumonia at slaughter.

PMID- 18336938
TI  - Analysis of reproducibility of respiration-triggered gated radiotherapy for lung
      tumors.
AB  - PURPOSE: Respiration-gated radiotherapy (RGRT) can decrease the toxicity of chemo
      radiotherapy (CT-RT) by allowing use of smaller treatment fields. RGRT requires a
      predictable relationship between tumor position and external surrogate, which
      must be verified during treatment. Time-integrated electronic portal imaging (TI
      EPI) identifies mean intra-fractional positions of moving structures, and was
      used to study reproducibility of anatomy during RGRT for lung tumors. MATERIALS
      AND METHODS: TI-EPIs were acquired using an amorphous silicon-based electronic
      portal imaging system (EPID, aS500) in continuous image acquisition mode in 11
      patients treated with audio-coached RGRT at end-inspiration. The Varian Real-time
      Position Management (RPM) system was used for 4DCT imaging and RGRT delivery. All
      TI-EPI portals were co-registered to corresponding digitally reconstructed
      radiographs (DRR) of the planning 4DCT using the spinal column. Displacements in
      tumor position or that of an adjacent bronchus during RGRT was measured relative
      to the reference structure on the DRR. RESULTS: Vertebra-matched portals revealed
      systematic (Sigma) and random (sigma) errors of 1.8 and 1.3mm in medial-lateral
      direction and 1.7 and 1.7 mm in cranial-caudal direction, indicating a
      reproducible tumor/bronchus position during the RPM-triggered gates. CONCLUSIONS:
      RGRT delivery at end-inspiration can achieve reproducible internal anatomy in
      'gated' fields delivered with audio-coaching.

PMID- 18336939
TI  - Energetic heavy ions overcome tumor radioresistance caused by overexpression of
      Bcl-2.
AB  - BACKGROUND AND PURPOSE: Overexpression of Bcl-2 is frequent in human cancers and
      has been associated with radioresistance. Here we investigated the potential
      impact of heavy ions on Bcl-2 overexpressing tumors. MATERIALS AND METHODS: Bcl-2
      cells (Bcl-2 overexpressing HeLa cells) and Neo cells (neomycin resistant gene
      expressing HeLa cells) exposed to gamma-rays or heavy ions were assessed for the
      clonogenic survival, apoptosis and cell cycle distribution. RESULTS: Whereas Bcl
      2 cells were more resistant to gamma-rays (0.2keV/microm) and helium ions
      (16.2keV/microm) than Neo cells, heavy ions (76.3-1610keV/microm) yielded similar
      survival regardless of Bcl-2 overexpression. Carbon ions (108keV/microm)
      decreased the difference in the apoptotic incidence between Bcl-2 and Neo cells,
      and prolonged G(2)/M arrest that occurred more extensively in Bcl-2 cells than in
      Neo cells. CONCLUSIONS: High-LET heavy ions overcome tumor radioresistance caused
      by Bcl-2 overexpression, which may be explained at least in part by the enhanced
      apoptotic response and prolonged G(2)/M arrest. Thus, heavy-ion therapy may be a
      promising modality for Bcl-2 overexpressing radioresistant tumors.

PMID- 18336940
TI  - Boron neutron capture therapy (BNCT) for glioblastoma multiforme: a phase II
      study evaluating a prolonged high-dose of boronophenylalanine (BPA).
AB  - BACKGROUND AND PURPOSE: To evaluate the efficacy and safety of boron neutron
      capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol
      for the boronophenylalanine-fructose (BPA-F) infusion. PATIENT AND METHODS: This
      phase II study included 30 patients, 26-69 years old, with a good performance
      status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body
      weight) was given i.v. over 6h. Neutron irradiation started 2h after the
      completion of the infusion. Follow-up reports were monitored by an independent
      clinical research institute. RESULTS: The boron-blood concentration during
      irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal
      brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4
      to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous
      problem, 5 patients were stricken by thromboembolism and 4 from abdominal
      disturbances in close relation to BNCT. Four patients displayed 9 episodes of
      grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of
      the 29 evaluable patients were dead. The median time from BNCT treatment to
      tumour progression was 5.8 months and the median survival time after BNCT was
      14.2 months. Following progression, 13 patients were given temozolomide, two
      patients were re-irradiated, and two were re-operated. Patients treated with
      temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of
      life analysis demonstrated a progressive deterioration after BNCT. CONCLUSION:
      Although, the efficacy of BNCT in the present protocol seems to be comparable
      with conventional radiotherapy and the treatment time is shorter, the observed
      side effects and the requirement of complex infrastructure and higher resources
      emphasize the need of further phase I and II studies, especially directed to
      improve the accumulation of (10)B in tumour cells.

PMID- 18336942
TI  - Cardiovascular indicators of disgust.
AB  - A bradycardia and an increasing parasympathetic activity are often recommended as
      characteristic physiological disgust reactions. However, findings concerning the
      influence of disgust on heart rate and autonomic control are heterogenous. Apart
      from this, only a few studies examined cardiovascular reactions to disgust,
      besides heart rate. The aim of this study is a differentiated description of
      cardiovascular reactions going along with disgust using impedance cardiography.
      Moreover, it will be surveyed if different cardiovascular responses are
      associated with content-specific disgust-inductions. One-hundred subjects watched
      three films: A neutral film (screensaver), a filmclip showing an amputation of
      the upper extremity and a filmclip displaying a person who is vomiting. The
      latter films are regarded as disease- and food-related disgust stimuli
      respectively, representing two superior disgust domains. Subjective,
      electrodermal and cardiovascular reactions to these films were compared using
      Repeated Measures ANOVAs. Strong subjective, electrodermal and cardiovascular
      reactions towards the filmclips with disgusting content were observed. The
      cardiovascular reactions of the disease- and food-related disgust stimuli
      differed in subjective and physiological parameters. Thus, a decrease in heart
      rate could only be observed as a response to disease-related disgust-induction.
      The observed differences are discussed as an endorsement for a domain-specific
      organisation of disgust reactions.

PMID- 18336941
TI  - Electrophysiological signatures: magnetoencephalographic studies of the neural
      correlates of language impairment in autism spectrum disorders.
AB  - While magnetoencephalography (MEG) is of increasing utility in the assessment of
      pediatric patients with seizure disorders, this reflects only a part of the
      clinical potential of the technology. Beyond epilepsy, a broad range of
      developmental psychiatric disorders require the spatial and temporal resolution
      of brain activity offered by MEG. This article reviews the application of MEG in
      the study of auditory processing as an aspect of language impairment in children.
      Specifically, the potential application of MEG is elaborated in autism spectrum
      disorders (ASD), a devastating disorder with prevalence of 1 in 150. Results
      demonstrate the sensitivity of MEG for detection of abnormalities of auditory
      processing in ASD ('electrophysiological signatures') and their clinical
      correlates. These findings offer promise for the comprehensive assessment of
      developmental neuropsychiatric disorders.

PMID- 18336943
TI  - Coupling kinematics of memory and kinematics of movement: the conditions for a
      psychological relativity.
AB  - The organization of spatial and temporal information relative to memory-movement
      interactions was studied in a recall task. Stimuli consisted of four different
      configurations of eight dots, presented sequentially. In two configurations, the
      stimuli were spatiotemporal congruent, with (constant or variable) inter-stimulus
      distances corresponding to (constant or variable) inter-stimulus time intervals.
      In the other two configurations, the stimuli were spatiotemporal incongruent,
      with (constant or variable) inter-stimulus distances not corresponding to
      (variable or constant) inter-stimulus time intervals. After a learning phase
      consisting of 20 presentations of the target configuration, participants
      performed a series of pointing movements to reproduce both spatial and temporal
      characteristics of the stimulus 60 times in succession without ever re-examining
      the target configuration. Classically, in incongruent spatiotemporal conditions,
      the reproduction of, respectively, constant distances or constant time intervals
      are strongly disturbed by the simultaneous perception of variable inter-stimulus
      time intervals (Tau effect) or variable distances (Kappa effect). We assume that
      these spatiotemporal dependencies, which occur when the response relates to one
      dimension only, crucially depend on the non-integration of motoric aspects in
      memory.

PMID- 18336944
TI  - Expression profiles of 10 circadian clock genes in human peripheral blood
      mononuclear cells.
AB  - The circadian clock system regulates daily rhythms of physiology and behavior.
      The mammalian master clock in the suprachiasmatic nuclei orchestrates these
      biological rhythms in peripheral tissues. Since blood is the most accessible
      tissue source, we sought to dissect the human circadian clock system by
      characterizing clock gene expression in human peripheral blood mononuclear cells
      (PBMCs) isolated from eight young, healthy subjects. By evaluating the temporal
      expression profiles of 10 circadian clock genes, we found that Period 1 (Per1),
      Per2, and Per3 are rhythmically expressed in human blood samples. Our results
      suggest that evaluating the rhythmic expression of human Per genes could reveal
      an individual's circadian phenotype.

PMID- 18336945
TI  - Neuromedin U inhibits inflammation-mediated memory impairment and neuronal cell
      death in rodents.
AB  - Neuromedin U (NmU) is a neuropeptide isolated first from porcine spinal cord and
      later from many species. Although NmU receptors exist in the hippocampus, their
      function is unclear. In the present study, we examined the effects of NmU on
      lipopolysaccharide (LPS)-induced memory impairment and neuronal death in mice. In
      the Y-maze test, LPS (10mug/mouse, i.c.v.) significantly decreased spontaneous
      alternation, an effect which was in turn inhibited by NmU (0.5nmol/mouse,
      i.c.v.). Real-time PCR-based experiments indicated that NmU did not affect the
      mRNA level of IL-1beta or IL-6 increased by LPS, whereas it increased that of
      brain-derived neurotrophic factor (BDNF) in the hippocampus. K252a, an inhibitor
      of tyrosine kinase, inhibited the anti-amnesic effects of NmU. Furthermore, LPS
      treated glia conditioned medium (GCM) induced neuronal death in cultured
      hippocampal neurons from E18 rats. Pretreatment with NmU of LPS-treated cultured
      glia prevented the effects of GCM. However, NmU had no effect on neuronal death
      induced by direct treatment of neurons with IL-1beta. We propose that NmU
      protects memory function and neuronal cell viability from neuroinflammation.
      These effects may be mediated by production of neuroprotective factors, such as
      BDNF, in glia.

PMID- 18336946
TI  - Hydrophobically modified glycol chitosan nanoparticles-encapsulated camptothecin
      enhance the drug stability and tumor targeting in cancer therapy.
AB  - To prepare a water-insoluble camptothecin (CPT) delivery carrier, hydrophobically
      modified glycol chitosan (HGC) nanoparticles were constructed by chemical
      conjugation of hydrophobic 5beta-cholanic acid moieties to the hydrophilic glycol
      chitosan backbone. Insoluble anticancer drug, CPT, was easily encapsulated into
      HGC nanoparticles by a dialysis method and the drug loading efficiency was above
      80%. CPT-encapsulated HGC (CPT-HGC) nanoparticles formed nano-sized self
      aggregates in aqueous media (280-330 nm in diameter) and showed sustained release
      of CPT for 1 week. Also, HGC nanoparticles effectively protected the active
      lactone ring of CPT from the hydrolysis under physiological condition, due to the
      encapsulation of CPT into the hydrophobic cores in the HGC nanoparticles. The CPT
      HGC nanoparticles exhibited significant antitumor effects and high tumor
      targeting ability towards MDA-MB231 human breast cancer xenografts subcutaneously
      implanted in nude mice. Tumor growth was significantly inhibited after i.v.
      injection of CPT-HGC nanoparticles at doses of 10 mg/kg and 30 mg/kg, compared to
      free CPT at dose of 30 mg/kg. The significant antitumor efficacy of CPT-HGC
      nanoparticles was attributed to the ability of the nanoparticles to show both
      prolonged blood circulation and high accumulation in tumors, as confirmed by near
      infrared (NIR) fluorescence imaging systems. Thus, the delivery of CPT to tumor
      tissues at a high concentration, with the assistance of HGC nanoparticles,
      exerted a potent therapeutic effect. These results reveal the promising potential
      of HGC nanoparticles-encapsulated CPT as a stable and effective drug delivery
      system in cancer therapy.

PMID- 18336947
TI  - Impaired peripheral circulation in lower-leg arteries caused by higher arterial
      stiffness and greater vascular resistance associates with nephropathy in type 2
      diabetic patients with normal ankle-brachial indices.
AB  - Diabetic nephropathy is a major cause of lower-limb amputation. We enrolled 250
      type 2 diabetic patients without apparent occlusive peripheral arterial disease
      (ankle-brachial indices >0.9) and 40 age-matched nondiabetic subjects
      consecutively admitted to our hospital. Flow volume and resistive index (RI), an
      index of vascular resistance, at the popliteal artery were evaluated using gated
      two-dimensional cine-mode phase-contrast magnetic resonance imaging. Brachial
      ankle pulse wave velocity (baPWV) was measured as an index of arterial
      distensibility. Flow volume was negatively correlated with both baPWV (p=0.0009)
      and RI (p<0.0001) among the patients. When the patients were grouped into four
      subgroups with or without albuminuria and renal insufficiency according to the
      levels of urinary albumin excretion rate (>or=20 or <20microg/min) and estimated
      glomerular filtration rate (eGFR) (<60 or >or=60ml/min/1.73m(2)), albuminuric
      patients with renal insufficiency (n=30) showed the lowest flow volume (p=0.0078)
      and the highest baPWV (p=0.0006) and RI (p=0.0274) among the groups. Simple
      linear regression analyses demonstrated that eGFR correlated positively with flow
      volume (p=0.0020) and negatively with baPWV (p=0.0258) and RI (p=0.0029) in
      patients with albuminuria (n=92), but not with normoalbuminuria (n=158). Impaired
      peripheral circulation in lower-leg arteries associates with nephropathy in
      diabetic patients even though they have normal ankle-brachial indices.

PMID- 18336948
TI  - High dose ursodeoxycholic acid for the treatment of primary sclerosing
      cholangitis.

PMID- 18336949
TI  - Rethinking policies for the retention of allied health professionals in rural
      areas: a social relations approach.
AB  - OBJECTIVE: Retaining allied health professionals in rural areas is a recognised
      problem. Generally the literature has concentrated on three elements:
      practitioner needs, community needs and organisational needs. There has been
      little attempt to focus other types of social relations in which health
      practitioner retention and recruitment takes place. The aim of this paper is to
      question the present dominant hierarchical approach taken in relation to the
      retention of allied health professionals in rural localities. METHODS: The data
      derives from a survey in Southwest Victoria, Australia. The sample was purposive
      rather than representative as it was intended to be exploratory in nature rather
      than definitive. RESULTS: The data indicates that there is a greater tendency for
      allied health professionals in private practice to be retained in rural areas
      than those in the public sector. CONCLUSION: The paper concludes by raising some
      questions about the pertinence of present models for regional health initiatives
      since they are locked into a bureaucratic model where relationships are
      hierarchical and asymmetrically controlled.

PMID- 18336950
TI  - Toll-like receptor and pattern sensing for evoking immune response.

PMID- 18336951
TI  - The TP53 Arg72Pro polymorphism and lung cancer risk in a population of Northern
      Spain.
AB  - SUMMARY: Polymorphisms in tumor suppressor genes might contribute to the
      individual susceptibility to develop different types of cancer. Alterations in
      genes involved in cell cycle regulation and apoptosis, as tumor suppressor gene
      TP53, can lead to malignant transformations increasing the risk of developing
      cancer. We have investigated effects of polymorphism Arg72Pro on lung cancer
      risk, focusing on smoking and histology. Our study is a hospital-based case
      control study designed with 589 lung cancer patients mainly with squamous cell
      carcinoma (215), adenocarcinoma (156) and small cell carcinoma (90), and 582
      control subjects, matched in ethnicity, age and gender. Genotypes were determined
      by PCR-RFLP and the results were analysed using multivariate unconditional
      logistic regression, adjusted for age, gender and smoking status. The analysis
      showed a statistically significant increase of lung cancer risk in Pro carriers
      (Arg/Pro and Pro/Pro) (adjusted OR=1.32; 95% CI=1.03-1.69), especially for ever
      smokers (adjusted OR=1.34; 95% CI=1.04-1.73), heavy smokers (adjusted OR=1.48;
      95% CI=1.01-2.16) and smokers of exclusively black tobacco (adjusted OR=1.45; 95%
      CI=1.04-2.00). Moreover, Pro carriers present an increased risk of developing
      small cell lung cancer (adjusted OR=1.70; 95% CI=1.07-2.69) and cancer in stage
      IV for NSCLC (adjusted OR=1.56; 95% CI=1.07-2.27). Our results suggest that
      polymorphism Arg72Pro in tumor suppressor gene TP53 increases the risk of lung
      cancer. The effect is especially strong for small cell lung cancer (SCLC) and
      heavy smokers.

PMID- 18336952
TI  - Acceptance of genetically modified foods: the relation between technology and
      evaluation.
AB  - This study investigates why consumers accept different genetically modified food
      products to different extents. The study shows that whether food products are
      genetically modified or not and whether they are processed or not are the two
      important features that affect the acceptance of food products and their
      evaluation (in terms of perceived healthiness, naturalness, necessity and
      tastiness). The extent to which these evaluation attributes and acceptance of a
      product are affected by genetic modification or processing depends on whether the
      product is negatively affected by the other technology: Any technological change
      to a 'natural' product (when nonprocessed products are genetically modified or
      when non-genetically modified products are processed) affect evaluation and
      acceptance stronger than a change to an technologically adapted product (when
      processed products are also genetically modified or vice versa). Furthermore,
      evaluation attributes appear to mediate the effects of genetic modification and
      processing on acceptance.

PMID- 18336953
TI  - Valproate-dependent transcriptional regulation of GLAST/EAAT1 expression:
      involvement of Ying-Yang 1.
AB  - Valproate, a widely used anti-epileptic drug also employed in the treatment of
      neurological diseases such as bipolar disorder and migraine, regulates the
      glutamatergic and GABAergic systems, although its effects in cell physiology have
      not been thoroughly characterized. High concentrations of glutamate reached
      during abnormal neurotransmission if not removed properly, become neurotoxic.
      Glutamate clearance is carried out by high affinity Na(+)-dependent glutamate
      transporter systems. The glutamate/aspartate transporter GLAST/EAAT1 plays the
      major role in glutamate removal and is regulated at different levels:
      transcription, post-translational modifications and cytoplasmic trafficking. The
      aim of this work was to gain insight into a plausible effect of valproate in
      GLAST function. Using cultured Bergmann glia cells from chick cerebellum we
      demonstrate here that valproate exposure elicits a dual regulatory effect on
      GLAST. In the short-term, valproate increases its Na(+)-dependent [(3)H]-d
      aspartate uptake activity in a cytochalasin B-sensitive manner. Interestingly, a
      synergism between valproate and a histone deacetylase inhibitor was observed.
      Long-term valproate treatment up-regulates chglast promoter activity, GLAST mRNA
      levels, GLAST molecules at the plasma membrane and its uptake activity.
      Furthermore, valproate induces histone 3 lysine 14 acetylation and regulates Ying
      Yang 1 (YY1) transcriptional repression on the chglast promoter. These results
      suggest that valproate elicits its effect through its histone deacetylase
      inhibitor properties.

PMID- 18336954
TI  - Synaptic contact number and size in stratum radiatum CA1 of APP/PS1DeltaE9
      transgenic mice.
AB  - Synaptic changes occur early in the course of Alzheimer's disease and are key to
      understanding the initial events in associated neurodegenerative processes. The
      quantitative analysis of synaptic morphology in transgenic mouse models of
      Alzheimer's disease can provide important insights into these processes. To this
      end, the total number and the distribution of the diameters of synaptic contacts
      in the stratum radiatum of the CA1 region of the hippocampus of 12-month-old
      APP/PS1DeltaE9 transgenic mice and wild type littermates have been evaluated by
      applying design-based stereological methods to material prepared for electron
      microscopy. Although there were no differences in the size of the synaptic
      contacts, the total number of synaptic contacts was significantly larger in the
      transgenic mice, suggesting that the transgenic effect at this age is
      synaptotrophic and that the presence of amyloid plaques and an elevated
      Abeta42/40 ratio are not necessarily detrimental to populations of synapses. The
      potential of this type of data in evaluating synaptic changes related to
      Alzheimer's disease is discussed and the methodology described in detail.

PMID- 18336955
TI  - No association of DAPK1 and ABCA2 SNPs on chromosome 9 with Alzheimer's disease.
AB  - Recently genetic variation in the DAPK1 and ABCA2 genes has been reported to be
      associated with late- and early-onset Alzheimer's disease (AD), respectively. We
      examined the most significant two single-nucleotide polymorphisms (SNPs) in DAPK1
      in a large case-control cohort of late-onset subjects and matched controls and
      one of the most significant SNPs in ABCA2 in a small set of early-onset subjects
      as well. We did not detect associations with AD for any variation.

PMID- 18336956
TI  - New diketone based vanadium complexes as insulin mimetics.
AB  - Since 1985, when Heyliger et al. first reported the in vivo insulin mimetic
      activity of oral vanadate, extensive studies exploring vanadium chemistry,
      including the synthesis of novel complexes and their biological effects both in
      vitro and in vivo have been pursued. Such complexes have emerged as possible
      potential agents for diabetes therapy. Among the several existing compounds,
      diketone based vanadium complexes have been chosen for the current study. Two new
      complexes namely bisdimethylmalonatooxovanadium(IV) and
      bisdiethylmalonatooxovanadium(IV) have been synthesized and characterized by UV
      visible, FTIR and mass spectral studies. The antidiabetic activity of the
      complexes was proved by animal study. The results show that the above complexes
      have comparable antidiabetic potential with respect to the standard drug as well
      as with bisacetylacetonatooxovanadium(IV) which has been studied earlier by Reul
      et al.

PMID- 18336957
TI  - Synthesis, crystal structure and anti-inflammatory properties of curcumin
      analogues.
AB  - Curcuminoids have been reported to possess multifunctional bioactivities,
      especially the ability to inhibit proinflammatory induction. Since it has been
      suggested that the seven-carbon beta-diketone linker in curcumin is responsible
      for its instability, nine mono-carbonyl five-carbon linker containing analogues
      were designed and synthesized. Their bioactivity against lipopolysaccharide
      induced TNF-alpha amd IL-6 secretion was evaluated by using mouse J774.1
      macrophages. The results showed that the 3'-methoxyl plays an important role in
      bioactivity and cyclohexanone containing analogues exhibited stronger
      inflammatory inhibition than acetone and cyclopentanone analogues. Subsequently
      the most active analogue 3c was determined using single-crystal X-ray
      diffraction. X-ray analysis and comparison with curcumin reveals that the
      presence of cyclohexanone in 3c, which remotely resembles the 6-membered ring in
      the enol tautomer in curcumin, may play an important role in the bioactivity. It
      is suggested that five-carbon linker analogues containing a cyclohexane ring
      which are synthetically assessable may be pharmacologically important.

PMID- 18336958
TI  - Clinical experience in mental health nursing: determining satisfaction and the
      influential factors.
AB  - Clinical exposure to the mental health environment has been identified as a major
      factor in promoting a more favourable attitude towards mental health nursing.
      However, little attention has been devoted to measuring specific aspects of the
      clinical placement experience. This paper presents the findings of a survey of
      703 undergraduate nursing students designed to measure satisfaction and identify
      factors influencing satisfaction (length and type of placement, time spent with a
      preceptor). A questionnaire was administered to undergraduate nursing students in
      Victoria, Australia, at the conclusion of their clinical experience in mental
      health. The findings demonstrate a high level of satisfaction, particularly in
      feeling welcomed, well oriented and supported, and opportunities for patient
      care. Students' views were influenced by the duration and type of placement and
      time spent with a preceptor. These findings provide valuable information about
      characteristics of a positive clinical experience that should be considered in
      structuring clinical placements in the mental health field.

PMID- 18336959
TI  - Augmentation of SIV DNA vaccine-induced cellular immunity by targeting the 4-1BB
      costimulatory molecule.
AB  - DNA vaccines are effective at inducing antigen-specific cellular immune
      responses. Approaches to improve these responses, however, are needed. We
      examined the effect of stimulating 4-1BB, an activation-inducible T-cell
      costimulatory receptor, by intravenously co-administering anti-human 4-1BB
      monoclonal antibody (mAb) in DNA-immunized cynomolgus macaques. Three groups of
      six cynomolgus macaques were immunized intramuscularly with a DNA vaccine
      encoding SIV Gag antigen (pSIVgag) at weeks 0, 4 and 8. At days 12, 15, and 19,
      six macaques received anti-4-1BB 4E9 mAb and six macaques received anti-4-1BB
      10C7 mAb. Treatment with 10C7 mAb led to a significant augmentation of SIV Gag
      specific IFN-gamma, granzyme B and perforin responses. Treatment with humanized
      4E9 mAb also resulted in an enhancement of SIV Gag-specific cellular responses
      but the magnitude was lower compared to animals receiving 10C7 mAb. These
      responses persisted up to week 40 and were mostly mediated by CD8(+) T cells.
      Treatment with anti-4-1BB mAb was more effective in driving the CD8(+) T cells
      toward a more differentiated CCR7(-)/CD45RA(+) effector state. This study
      demonstrates that targeting the 4-1BB molecule in vivo results in an enhanced and
      long-lasting cellular immune response. 4-1BB stimulation may be a promising
      approach to enhance the effectiveness of DNA vaccines.

PMID- 18336960
TI  - WHO Working Group on revision of the Manual of Laboratory Methods for Testing DTP
      Vaccines-Report of two meetings held on 20-21 July 2006 and 28-30 March 2007,
      Geneva, Switzerland.
AB  - This report reflects the discussion and conclusions of a WHO group of experts
      from National Regulatory Authorities (NRAs), National Control Laboratories
      (NCLs), vaccine industries and other relevant institutions involved in
      standardization and control of diphtheria, tetanus and pertussis vaccines (DTP),
      held on 20-21 July 2006 and 28-30 March 2007, in Geneva Switzerland for the
      revision of WHO Manual for quality control of DTP vaccines. Taking into account
      recent developments and standardization in quality control methods and the
      revision of WHO recommendations for D, T, P vaccines, and a need for updating the
      manual has been recognized. In these two meetings the current situation of
      quality control methods in terms of potency, safety and identity tests for DTP
      vaccines and statistical analysis of data were reviewed. Based on the WHO
      recommendations and recent validation of testing methods, the content of current
      manual were reviewed and discussed. The group agreed that the principles to be
      observed in selecting methods included identifying those critical for assuring
      safety, efficacy and quality and which were consistent with WHO
      recommendations/requirements. Methods that were well recognized but not yet
      included in current Recommendations should be taken into account. These would
      include in vivo and/or in vitro methods for determining potency, safety testing
      and identity. The statistical analysis of the data should be revised and updated.
      It was noted that the mouse based assays for toxoid potency were still quite
      widely used and it was desirable to establish appropriate standards for these to
      enable the results to be related to the standard guinea pig assays. The working
      group was met again to review the first drafts and to input further suggestions
      or amendments to the contributions of the drafting groups. The revised manual was
      to be finalized and published by WHO.

PMID- 18336961
TI  - Kinetics of asthma- and allergy-associated immune response gene expression in
      peripheral blood mononuclear cells from vaccinated infants after in vitro re
      stimulation with vaccine antigen.
AB  - The global expression of immune response genes in infants after vaccination and
      their role in asthma and allergy is not clearly understood. Pharmacogenomics is
      ideally suited to study the involved cellular responses, since the expression of
      thousands of genes can be assessed simultaneously. Here, array technology was
      used to assess the expression kinetics of immune response genes with association
      to asthma and allergy in peripheral blood mononuclear cells (PBMC) of five
      healthy infants after vaccination with Infanrix-Polio+Hib. At 12h after in vitro
      re-stimulation of the PBMC with pertussis toxin (PT) antigen, 14 immune response
      pathways, 33 allergy-related and 66 asthma-related genes were found activated.

PMID- 18336962
TI  - Development of Eurasian H7N7/PR8 high growth reassortant virus for clinical
      evaluation as an inactivated pandemic influenza vaccine.
AB  - Avian-to-human transmission of the high pathogenicity (HP) H7N7 subtype avian
      influenza viruses in the Netherlands during 2003 caused zoonotic infections in 89
      people, including a case of acute fatal respiratory distress syndrome. Public
      health emergency preparedness against H7N7 avian influenza viruses with pandemic
      potential includes the development of vaccine candidate viruses. In order to
      develop a high growth reassortant vaccine candidate virus, low pathogenicity (LP)
      A/mallard/Netherlands/12/2000 (H7N3) and A/mallard/Netherlands/2/2000 (H10N7)
      strains were selected as donors of the H7 haemagglutinin and N7 neuraminidase
      genes, respectively. The donor viruses exhibited high amino acid sequence
      homology with the surface glycoproteins of A/Netherlands/219/03 H7N7 virus
      (NL219), an isolate recovered from the fatal human case. Adhering to the seasonal
      influenza vaccine licensure regulations, we generated a H7N7/PR8 reassortant
      containing desired surface glycoprotein genes from the mallard viruses and
      internal genes of A/Puerto Rico/8/34 human vaccine strain (H1N1). Antigenic
      analysis revealed that the vaccine candidate virus confers broad antigenic cross
      reactivity against contemporary Eurasian and the North American H7 subtype human
      isolates. Mice immunized with formalin inactivated (FI) H7N7/PR8 whole virus
      vaccine with or without aluminum hydroxide adjuvant conferred clinical protection
      from mortality and reduced pulmonary replication of the NL219 challenge virus.
      The FI H7N7/PR8 whole virus vaccine also afforded cross-protection in mice at the
      pulmonary level against antigenically distinct North American LP A/Canada/444/04
      (H7N3) human isolate. The vaccine candidate virus satisfied the agricultural
      safety requirements for chickens, proved safe in mice, and has entered in phase-I
      human clinical trial in the United States.

PMID- 18336963
TI  - Long-term antibody persistence induced by a combined hepatitis A and B vaccine in
      children and adolescents.
AB  - Two cohorts, comprising of subjects aged 1-6 years and 6-15 years were vaccinated
      with Twinrix according to a 0-, 1- and 6-month schedule. The 1-6 years cohort was
      followed up for 7.5 years and the 6-15 years cohort for 10 years. At the latest
      follow-up time point, all subjects were seropositive for anti-HAV antibodies,
      while 86.5% (32/37) and 95.5% (21/22) had anti-HBs >or= 10 mIU/ml in the 1-6
      years and in the 6-15 years cohort. The geometric mean concentrations (GMCs;
      mIU/ml) were 233 and 680 for anti-HAV antibodies, and 147 and 165 for anti-HBs
      antibodies, in the 1-6 years and 6-15 years cohorts, respectively. The high
      persistence of circulating anti-HAV and anti-HBs antibodies in children and
      adolescents demonstrates the long-term protection offered by Twinrix in these age
      groups.

PMID- 18336964
TI  - Therapeutic vaccination against malignant gliomas based on allorecognition and
      syngeneic tumor antigens: proof of principle in two strains of rat.
AB  - In the present study we investigated whether allogeneic glioma cells can be
      utilized to evoke prophylactic or therapeutic immune-mediated elimination of
      syngeneic glioma in two rat strains. Fisher 344 and Sprague-Dawley (SD) rats were
      injected with two syngeneic glioma cell lines, 9L and C6, respectively, resulting
      in progressive tumor growth. 9L is syngeneic to the Fisher 344 and allogeneic to
      the SD rats, while C6 cells are syngeneic to SD rats and allogeneic to Fisher 344
      rats. Both rat strains were subcutaneously injected with their respective
      allogeneic tumor cells, which proved unable to grow progressively. The allogeneic
      cells were either rejected immediately in SD rats or within 25 days in Fisher
      rats, after limited tumor outgrowth. Both rat strains were subsequently
      challenged with their respective syngeneic glioma tumor cells and once more 10
      days later with a fivefold higher dose. SD rats, even after reinjection with five
      times the original dosage of C6 cells, remained tumor free for at least 360 days.
      Similarly, Fisher rats, after initially rejecting allogeneic tumors, failed to
      develop syngeneic tumors. To determine anti-tumor immunity against established
      glioma tumors under more demanding therapeutic conditions, rats were first
      injected subcutaneously with their respective syngeneic tumor and vaccinated once
      or repeatedly (at 5-day intervals) with a mixture of the allogeneic or xenogeneic
      cells, with or without a lysate from the same syngeneic tumor, which served as a
      therapeutic vaccine preparations. The control group received either no treatment
      or syngeneic instead of allogeneic cells. In both strains of rats, we
      demonstrated that the therapeutically vaccinated groups were able to
      significantly reduce tumor growth, while complete rejection of tumors was noted
      in the SD rats. Immunization with syngeneic tumor cells alone failed to evoke
      anti-tumor immunity. We conclude that therapeutic immunization with a combination
      of allogeneic cells and syngeneic lysates induces rejection of malignant gliomas
      and offers a protective effect against challenge with syngeneic tumor cells. This
      immunization approach may prove useful as a post-surgery adjuvant therapy in
      future cancer treatment protocols, or even as a stand-alone therapeutic tumor
      vaccination.

PMID- 18336965
TI  - Influenza vaccination of recommended adult populations, U.S., 1989-2005.
AB  - OBJECTIVE: To assess influenza vaccination coverage among recommended adult
      populations in the United States. METHODS: Data from the 1989 to 2005 National
      Health Interview Surveys (NHISs), weighted to reflect the civilian, non
      institutionalized U.S. population, were analyzed to determine self-reported
      levels of influenza vaccination among persons aged >or=65 years, persons with
      high-risk conditions, health care workers (HCW), pregnant women, and persons
      living in households with at least one identified person at high risk of
      complications from influenza infection. We stratified data by race/ethnicity to
      identify racial/ethnic disparities. RESULTS: Vaccination coverage levels among
      all recommended adult populations peaked in 2004, then declined in 2005 in
      association with the 2004-2005 vaccine shortage. Coverage for adults >or=65 years
      of age increased from 30.1% (95% confidence interval [CI]: 28.8-31.3) in 1989 to
      70.0% (68.0-71.5) in 2004. In 2004, coverage was 40.7% (39.0-42.5) for all adults
      50-64 years, 27.2% (24.6-29.9) for adults aged 18-49 years with high-risk
      conditions, 43.2% (39.9-46.6) for health care workers, 21.1% (19.1-23.4) for non
      high-risk adults aged 18-64 years with a high-risk household member, and 14.4%
      (8.8-22.9) for pregnant women. Among each of the recommended adult sub-groups,
      vaccination coverage was higher for non-Hispanic whites compared to minority
      groups. CONCLUSIONS: By 1997, influenza vaccination coverage had exceeded the
      national 2000 objective of 60% among persons aged >or=65 years, but by 2004 still
      remains well below the national 2010 target of 90%. Coverage levels for other
      groups targeted for influenza vaccination also are far short of the Healthy
      People 2000 and 2010 goals of 60% for persons aged 18-64 years with high-risk
      conditions, health care workers, and pregnant women. A concerted effort to
      increase provider adoption of standards for adult immunization, public awareness,
      and stable vaccine supplies are needed to improve influenza vaccination rates
      among recommended groups, and to reduce racial and ethnic disparities.

PMID- 18336966
TI  - Short- and long-term immunogenicity and protection induced by non-replicating
      smallpox vaccine candidates in mice and comparison with the traditional 1st
      generation vaccine.
AB  - This study assessed three non-replicating smallpox vaccine candidates (modified
      vaccinia Ankara (MVA), NYVAC and HR) for their immunogenicity and ability to
      protect mice against an intranasal cowpox virus challenge and compared them with
      the traditional replicating vaccine. A single immunisation with the non
      replicating vaccines induced a complete protection from death at short-term, but
      was not fully protective when mice were challenged 150 days post-vaccination with
      protection correlated with the specific neutralizing antibodies and CD4(+) T
      cells responses. Prime-boost vaccination enabled effective long-term protection
      from death for mice vaccinated with MVA, but protection from disease and CD4(+) T
      cell level were lower than the ones induced by the traditional vaccine over the
      long-term period. Further investigations are necessary with MVA to determine the
      optimal conditions of immunisation to induce at long-term immunogenicity and
      protection observed with the 1st generation smallpox vaccine.

PMID- 18336967
TI  - Effects of repeated cycles of sterilisation on the mechanical characteristics of
      titanium miniplates for osteosynthesis.
AB  - AIM: This study investigates the changes occurring in the mechanical
      characteristics of osteosynthesis titanium miniplates when exposed to repeated
      sterilization cycles. METHODS: For this study Medicon (c) titanium miniplates
      were used. The characteristics of miniplates were evaluated using the Penetration
      Resistance test, MSC/Pal2 Software, and the Finite Elements Method (F.E.M.).
      Surface roughness measurements were also carried out. Statistical analysis was
      conducted using the One way ANOVA model. The significance level was set at >0.05.
      RESULTS: The one way ANOVA analysis between HV value and increased sterilization
      cycles showed P>0.029; between the Ra value and increased sterilization cycles it
      was P>0.325; between the Rq value and increased sterilization cycles it was
      P>0.703. The Finite Element Model shows an amplified deformed shape of the
      miniplate at a load of 196 [N]. At this load value the equivalent 'von Mises
      stress' reaches the value of sigmaP0.2, shown by the ASTM F 67-95 standard.
      Stress distribution comparison between the six-holed plate and the equivalent
      straight miniplate shows more consistent behaviour for the Medicon (c) miniplate.
      The rigidity of the Medicon (c) miniplate is 14.46, lower than that for the
      equivalent straight miniplate (R=23.4). The ANOVA analysis between the break load
      and increased sterilization cycles showed P>0.175; between the break position and
      increased sterilization cycles it showed P>0.016. CONCLUSIONS: Experimental
      static tests have shown that all tested miniplates did not have notable
      differences and this suggests that sterilization cycles do not affect mechanical
      characteristics.

PMID- 18336968
TI  - The tear-drop sign: a trap door for the unwary?
AB  - We describe a patient who presented with features suggestive of an orbital
      blowout fracture. These were apparently confirmed on imaging and operation was
      planned. However, further radiological and orthoptic opinions diagnosed both a
      pre-existing eye condition and benign antral mucosal disease that had been
      misinterpreted as a single acute problem. The patient was discharged with no need
      for intervention.

PMID- 18336969
TI  - Reconstruction of curved mandibular angle defects using a new internal transport
      distraction device: an experiment in goats.
AB  - A new internal distraction device, comprising a square-bodied bow, a transport
      plate, a traction mechanism, and two stabilisers, was developed to allow
      transportation of bone around an arc. Eight adult goats were studied. A curved
      mandibulectomy 3cm long was made on the mandibular angle. The distractor was
      implanted to restore the defect. The bone was distracted at a rate of 1mm per day
      after a 5-day latent period. Distraction lasted 25 to 32 days. Curvilinear
      distraction was successful in six of the eight goats. After consolidation periods
      of four or eight weeks, smooth curved bone masses were restored in the distracted
      areas. Radiographically, there was considerable bone density in the distraction
      area and opaque columns streamed in the direction of distraction. Histological
      examination showed membranous bony regeneration in the restored bone. These
      results suggest that restoration of curved bone defects using the new internal
      transport distraction device was feasible in goats.

PMID- 18336970
TI  - Health-related quality of life in Nigerian patients with facial trauma and
      controls: a preliminary survey.
AB  - We examined the health-related quality of life (HR QoL) of patients with facial
      trauma and compared it with that of healthy controls; temporal changes in HR QoL
      of patients over 12 weeks compared with baseline values; and whether the risk of
      depression could be identified by baseline HR QoL. For 26 months we recruited 126
      consecutive patients with facial injuries and 126 age and sex-matched healthy
      controls for the study. Enrollment criteria included age 18 years and over,
      Glasgow coma scale score on admission of 12 and over, and duration of stay of
      more than 24 hours. HR QoL was measured using the 26-item World Health
      Organization Quality of Life Questionnaire (WHO QoL-Bref), and depression was
      measured with the Hospital Anxiety and Depression Scale (HADS). Scores in all
      domains of the WHO QoL-Bref (physical, psychological, social relations, and
      environment) were considerably reduced in injured patients compared with
      controls. During follow up there were improvements only in the domains of
      physical health and environment, but not in psychological health. There was a
      significant reduction in the HR QoL domain of social relationships with time. The
      regression equation for all four QoL domains as predictors was significantly
      related to depression scores throughout the study period. Patients with facial
      injuries are at risk of poor QoL after trauma. There was a high incidence of
      depression throughout the follow-up period, and poor QoL at baseline predicted
      depression during follow-up.

PMID- 18336971
TI  - Septa within the sinus: effect on elevation of the sinus floor.
AB  - Elevation of the sinus floor allows the correct number and length of oral
      implants to be placed. The sinus membrane is dissected blindly, usually by a
      crestal approach, but several internal configurations of the maxillary sinus or
      intrasinus septa can cause problems. We studied 150 sinuses from 40 male
      cadavers, and 35 randomised male patients by anatomical dissection and computed
      tomography. Forty-six subjects (61%) had no bony septa or had septa less than
      4mm. Twenty-nine (39%) had bony septa of which seven were incomplete, one had a
      complete bony septum in each maxillary sinus, and 20 had symmetrical bony septa.
      We present the results of a study of bony intramaxillary sinus septa and the
      potential problems they can cause during elevation of the sinus floor.

PMID- 18336972
TI  - Chelating agents and the environment.

PMID- 18336973
TI  - Trends of nitrogen in air and precipitation: model results and observations at
      EMEP sites in Europe, 1980--2003.
AB  - We analyze trends of some nitrogen compounds using long-term measurements and
      results from the EMEP (co-operative programme for monitoring and evaluation of
      the long-range transmissions of air pollutants in Europe) chemical transport
      model at EMEP sites. We find statistically significant declines at the majority
      of sites for NH(x) (sum of ammonia and ammonium) in air and for nitrate and
      ammonium in precipitation, but only at a few sites for xNO3 (sum of nitrate and
      nitric acid) in air. Model calculations and measurements give similar results. We
      demonstrate that the lack of trends for xNO3 in air at least partly can be
      attributed to a shift in the equilibrium between nitric acid and ammonium nitrate
      towards particulate phase, caused by reductions in the sulfur dioxide emissions.

PMID- 18336974
TI  - Comparing sense of coherence, depressive symptoms and anxiety, and their
      relationships with health in a population-based study.
AB  - The strong negative correlations observed between the sense of coherence (SOC)
      scale and measures of depression and anxiety raise the question of whether the
      SOC scale inversely measures the other constructs. The main aim of the present
      study was to examine the discriminant validity of the three measures by comparing
      their associations with health indicators and behaviours. The participants were
      25 to 74-year-old Finnish men (n=2351) and women (n=2291) from the National
      Cardiovascular Risk Factor Survey conducted in 1997. The SOC scale had high
      inverse correlations with both depression (r=-0.62 among both men and women) and
      anxiety measures (r=-0.57 among the men and r=-0.54 among the women). Although
      confirmatory factor analyses suggested that it was possible to differentiate
      between SOC, cognitive depressive symptoms and anxiety, the estimated
      correlations were even higher than those mentioned above. Education was related
      only to SOC, but the associations of SOC, cognitive depressive symptoms and
      anxiety with self-reported and clinically measured health indicators (body mass
      index, blood pressure, cholesterol) and health behaviours were almost identical.
      The variation in the lowest SOC tertile was more strongly associated with health
      variables than in the highest tertile. To conclude, the size of the overlap
      between the SOC and depression scales was the same as between depression and
      anxiety measures. This indicates that future studies should examine the
      discriminant validity of different psychosocial scales more closely, and should
      compare them in health research in order to bring parallel concepts into the same
      scientific discussion.

PMID- 18336975
TI  - The effect of income and occupation on body mass index among women in the Cebu
      Longitudinal Health and Nutrition Surveys (1983-2002).
AB  - We assessed the effects of changes in income and occupational activities on
      changes in body weight among 2952 non-pregnant women enrolled in the Cebu
      Longitudinal Health and Nutrition Surveys between 1983 and 2002. On average, body
      mass index (BMI) among women occupied in low activities was 0.29 kg/m(2)
      (standard error 0.11) larger compared to women occupied in heavy activities. BMI
      among women involved in medium activities was on average 0.12 kg/m(2) (standard
      error 0.05) larger compared to women occupied in heavy activities. A one-unit
      increase in log household income in the previous survey was associated with a
      small and positive change in BMI of 0.006 kg/m(2) (standard error 0.02) but the
      effect was not significant. The trend of increasing body mass was higher in the
      late 1980s than during the 1990s. These period effects were stronger for the
      women who were younger at baseline and for women with low or medium activity
      levels. Our analysis suggests a trend in the environment over the last 20 years
      that has increased the susceptibility of Filipino women to larger body mass.

PMID- 18336976
TI  - Engaging citizens: lessons from building Brazil's national health system.
AB  - Brazil's Sistema Unico de Saude (SUS), a universal, publicly-funded, rights-based
      health system, designed and put in place in an era where neo-liberal reforms
      elsewhere in the world have driven the marketization of health services, offers
      important lessons for future health systems. In this article, we focus on the
      innovative institutional mechanisms for popular involvement and accountability
      that are part of the architecture for governance of the SUS. We argue that these
      mechanisms of public involvement hold the potential to sustain a compact between
      state and citizens and ensure the political momentum required to broaden access
      to basic health services, while at the same time providing a framework for the
      emergence of "regulatory partnerships" capable of managing the complex reality of
      pluralistic provision and multiplying sources of health expertise in a way which
      ensures that the needs and rights of poor and marginalised citizens are not
      relegated to the periphery of a segmented health system.

PMID- 18336977
TI  - The health professions and the performance of future health systems in low-income
      countries: support or obstacle?
AB  - This paper discusses the present and future role of the health professions in
      health services delivery systems in low-income countries. Unlike richer
      countries, most low-income countries do not have a tradition of labour market
      regulation and the capacity of the professions themselves to regulate the
      provision of health services by their members tends to be weak. The paper looks
      at the impact of professional monopolies on the performance of health services
      delivery systems, e.g. equity of access, effectiveness of services, efficiency in
      the use of scarce resources, responsiveness to users' needs, including protection
      against the financial impact of utilising health services. It identifies issues
      which policy-makers face in relation to opening the health labour market while
      guaranteeing the safety and security of services provided by professionals. The
      suggestion is made that a "social contract", granting privileges of practice in
      exchange of a commitment to actively maintain and enhance the quality of their
      services, may be a viable course of action. This would require that the actors in
      the policy process collaborate in strengthening the capacity of regulatory
      agencies to perform their role.

PMID- 18336978
TI  - Biomedical scientists' perception of the social sciences in health research.
AB  - The growing interest in interdisciplinary research within the Canadian health
      sciences sector has been manifested by initiatives aimed at increasing the
      involvement of the social sciences in this sector. Drawing on Bourdieu's concept
      of field and Knorr-Cetina's concept of epistemic culture, this study explores the
      extent to which it is possible for the social sciences to integrate into, and
      thrive in, a field in which the experimental paradigm occupies a hegemonic
      position. Thirty-one semi-structured interviews were conducted to explore
      biomedical scientists' receptiveness toward the social sciences in general and to
      qualitative research in particular. We found that these respondents exhibited a
      predominantly negative posture toward the social sciences; however, we also found
      considerable variation in their judgments and explanations. Eight biomedical
      scientists tended to be receptive to the social sciences, 7 ambivalent, and 16
      unreceptive. The main rationale expressed by receptive respondents is that the
      legitimacy of a method depends on its capacity to adequately respond to a
      research question and not on its conformity to the experimental canon.
      Unreceptive respondents maintained that the social sciences cannot generate valid
      and reliable results because they are not conducive to the experimental design as
      a methodological approach. Ambivalent respondents were characterized by their
      cautiously accepting posture toward the social sciences and, especially, by their
      reservations about qualitative methods. Based on the biomedical scientists'
      limited receptiveness, we can anticipate that the growth of the social sciences
      will continue to meet obstacles within the health research field in the near
      future in Canada.

PMID- 18336979
TI  - Behavioral and ERP measures of holistic face processing in a composite task.
AB  - Holistic processing of faces is characterized by encoding of the face as a single
      stimulus. This study employed a composite face task to examine whether holistic
      processing varies when attention is restricted to the top as compared to the
      bottom half of the face, and whether evidence of holistic processing would be
      observed in event-related potentials. Analyses of behavioral data showed that
      spatial misalignment of the face halves disrupted holistic processing and
      enhanced detection of repeated attended halves. Effects of misalignment on the
      N170, VPP and N250 ERP components resembled effects of face inversion. Attention
      to the top half of the face was associated with faster P1, N170, VPP, and P2
      latencies than attending to the bottom, suggesting automatic processing of the
      eye region. Further, N170 latency effects suggested that structural encoding of
      the face is facilitated during holistic processing. N250 latency effects
      reflected task difficulty. Finally, an overall right hemispheric asymmetry was
      most pronounced when holistic face processing was greatest. Results are discussed
      in light of recent proposals that holistic face processing is a subtype of
      configural face processing.

PMID- 18336980
TI  - Role of the p50 subunit of NF-kappaB in vitamin E-induced changes in mice treated
      with the peroxisome proliferator, ciprofibrate.
AB  - Peroxisome proliferators (PPs) are a diverse class of chemicals, which cause a
      dramatic increase in the size and number of hepatic peroxisomes in rodents and
      eventually lead to the development of hepatic tumors. Nuclear factor-kappaB (NF
      kappaB) is a transcription factor activated by reactive oxygen and is involved in
      cell proliferation and apoptosis. Previously we found that the peroxisome
      proliferator ciprofibrate (CIP) activates NF-kappaB and that dietary vitamin E
      decreases CIP-induced NF-kappaB DNA binding. We, therefore, hypothesized that
      inhibition of NF-kappaB by vitamin E is necessary for effects of vitamin E on CIP
      induced cell proliferation and the inhibition of apoptosis by CIP. Sixteen B6129
      female mice (p50+/+) and twenty mice deficient in the p50 subunit of NF-kappaB
      (p50-/-) were fed a purified diet containing 10 or 250mg/kg vitamin E (alpha
      tocopherol acetate) for 28 days. At that time, half of the mice were placed on
      the same diet with 0.01% CIP for 10 days. CIP treatment increased the DNA binding
      activity of NF-kappaB and cell proliferation, but had no significant effect on
      apoptosis. Compared to wild-type mice, the p50-/- mice had lower NF-kappaB
      activation, higher basal levels of cell proliferation and apoptosis, and a lower
      ratio of reduced glutathione to oxidized glutathione (GSH/GSSG). There was
      approximately a 60% reduction in cell proliferation in the CIP-treated p50-/-
      mice fed higher vitamin E in comparison to the p50-/- mice fed lower vitamin E.
      Dietary vitamin E also inhibited the DNA binding activity of NF-kappaB, increased
      apoptosis, and increased the GSH/GSSG ratio. This study shows the effects of
      vitamin E on cell growth parameters do not appear to be solely through decreased
      NF-kappaB activation, suggesting that vitamin E is acting by other molecular
      mechanisms.

PMID- 18336981
TI  - Chronic ethanol ingestion alters xenobiotic absorption through the skin:
      potential role of oxidative stress.
AB  - Alcohol ingestion is correlated with several skin disorders and it has been
      proposed that changes in skin properties may be an early indicator of alcohol
      misuse. Topically applied ethanol is an effective transdermal penetration
      enhancer; however, little is known about the effects of chronic ethanol ingestion
      on skin. Rats were pair fed a diet containing 36% ethanol for twelve weeks. The
      animals were then switched to a non-ethanol diet and were monitored for up to
      four weeks. Non-invasive measurements for changes in dermal blood flow using
      laser Doppler velocimetry (LDV), damage to skin barrier via transepidermal water
      loss (TEWL) and changes in skin moisture content were obtained for the
      experimental duration. At 0, 1 day or 1, 2, 3, 4 weeks after alcohol removal rats
      were euthanized and their skin was analyzed for alcohol and aldehyde
      dehydrogenase, and lipid peroxidation. Transdermal penetration of the herbicide
      paraquat, industrial solvent dimethyl formamide (DMF), insect repellant N,N
      diethyl-m-toluamide (DEET) and herbicide 2,4-dichlorophenoxyacetic acid (2,4-D)
      was also determined. Transdermal absorption, LDV, TEWL, skin alcohol and aldehyde
      dehydrogenase, as well as lipid peroxidation significantly increased after
      continuous ethanol exposure (p<0.05). These factors remain elevated for up to
      four weeks after termination of ethanol consumption, showing that skin changes
      induced by alcohol are not immediately reversible and reflect fundamental changes
      in the skin itself. This work provides a starting point for examining the link
      between ethanol ingestion and skin disorders associated with alcohol use.

PMID- 18336982
TI  - Possible role for early-life immune insult including developmental immunotoxicity
      in chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME).
AB  - Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME) in
      some countries, is a debilitating disease with a constellation of multi-system
      dysfunctions primarily involving the neurological, endocrine and immune systems.
      While substantial information is available concerning the complex dysfunction
      associated symptoms of CFS, environmental origins of the disease have yet to be
      determined. Part of the dilemma in identifying the cause(s) has been the focus on
      biomarkers (hormones, neurotransmitters, cytokines, infectious agents) that are
      contemporary with later-life CFS episodes. Yet, recent investigations on the
      origins of environmental diseases of the neurological, endocrine, reproductive,
      respiratory and immune systems suggest that early life toxicologic and other
      insults are pivotal in producing later-life onset of symptoms. As with autism and
      childhood asthma, CFS can also occur in children where the causes are certainly
      early-life events. Immune dysfunction is recognized as part of the CFS phenotype
      but has received comparatively less attention than aberrant neurological or
      endocrine function. However, recent research results suggest that early life
      immune insults (ELII) including developmental immunotoxicity (DIT), which is
      induced by xenobiotics, may offer an important clue to the origin(s) of CFS. The
      developing immune system is a sensitive and novel target for environmental insult
      (xenobiotic, infectious agents, stress) with major ramifications for postnatal
      health risks. Additionally, many prenatal and early postnatal neurological
      lesions associated with postnatal neurobehavioral diseases are now recognized as
      linked to prenatal immune insult and inflammatory dysregulation. This review
      considers the potential role of ELII including DIT as an early-life component of
      later-life CFS.

PMID- 18336983
TI  - Adult derived mononuclear bone marrow cells improve survival in a model of
      acetaminophen-induced acute liver failure in rats.
AB  - INTRODUCTION: Acute liver failure (ALF) is characterized by a rapid loss of
      hepatic function, with high mortality. Acetaminophen (APAP) intoxication and
      viral hepatitis are common causes of ALF. Several studies have shown the capacity
      of adult bone marrow cells to differentiate in hepatocytes, suggesting their use
      for treating ALF. AIM: In the present study, we tested the use of adult derived
      mononuclear bone marrow fraction to improve the survival of Wistar rats with APAP
      induced ALF. METHODS: Forty-eight female Wistar rats pre-induced with
      phenobarbital were given APAP in a single dose of 1g/kg via intraperitoneal
      injection. Bone marrow mononuclear cells were purified from male rats using
      FICOLL gradient and injected through the portal vein in a volume of 0.2mL
      containing 1x10(6) cells stained with DAPI. Treatment was administered 24h after
      APAP injection. The sham group (n=24), received 0.2mL of saline through the
      portal vein 24h after APAP administration. Survival, liver histology and ALT
      levels were observed. RESULTS: Survival 72h post-APAP administration was 33% in
      the sham group and 70.8% in the group receiving bone marrow cells. Liver
      histology in treated animals showed less intense necrosis and the presence of
      DAPI-positive cells. CONCLUSIONS: We have shown that bone marrow derived cells
      are capable of significantly increasing the survival rate of APAP-induced ALF in
      37.5% (95% CI, 27.8-40.3%).

PMID- 18336984
TI  - Increase in intracellular free/bound NAD[P]H as a cause of Cd-induced oxidative
      stress in the HepG(2) cells.
AB  - The present study shows the use of confocal autofluorescence spectroscopy coupled
      with the time-resolved fluorescence decay analysis to measure changes in
      FAD/NAD[P]H and free/bound NAD[P]H in HepG(2) cells at 0.5, 1.5, 3 and 4.5h after
      exposure to cadmium chloride (Cd). These changes were compared to changes in
      GSSG/GSH and production of reactive oxygen radicals (ROS) production. The results
      demonstrated that both FAD/NAD[P]H and GSSG/GSH increased significantly upon
      exposure to Cd. The change in GSSG/GSH occurred as early as 1.5h after treatment
      while the change in FAD/NAD[P]H did not occur until 3h after exposure. Production
      of ROS was also increased at 1.5h. The ratio of free/bound NAD[P]H was studied.
      It was demonstrated that free/bound NAD[P]H increased significantly as early as
      0.5h and remained elevated until 4.5h after treatment with Cd. The present study
      provides novel data to show that changes in NAD[P]H metabolism precedes the
      increase in ROS production and cellular oxidative stress (increase GSSG/GSH,
      FAD/NAD[P]H). It is suggested that Cd causes a release of NAD[P]H, an important
      cofactor for electron transfer, from its normal protein binding sites. This may
      result in a disruption of the activity of the enzyme and proteins, and may lead
      to the subsequent toxic events.

PMID- 18336985
TI  - Shear strength evaluation of composite-composite resin associations.
AB  - OBJECTIVE: The aim of this study was to investigate the shear strength between
      distinct associations of different commercial composite resins and their fracture
      modes. METHODS: Nine composite-composite associations (n=90) were prepared for
      shear strength evaluation and separated into the following groups: Z/Z (Filtek
      Z250 UD+Filtek Z250 A2); Z/D (Filtek Z250 UD+Durafill VS A2); Z/S (Filtek Z250
      UD+Filtek Supreme YT); C/C (Charisma OA2+Charisma A2); C/D (Charisma OA2+Durafill
      VS A2); C/S (Charisma OA2+Filtek Supreme YT); H/H (Herculite XRV B2D+Herculite
      XRV B2E); H/D (Herculite XRV B2D+Durafill VS A2); H/S (Herculite XRV B2D+Filtek
      Supreme YT). Shear tests were carried out using universal mechanical test
      equipment with a load of 200kgf and speed of 0.5mm/min. Ultimate shear strength
      data (MPa) from all tested groups were submitted to analysis of variance (one-way
      ANOVA) and the Tukey test. The fractured surfaces of the test samples were
      visually evaluated by binocular stereomicroscope at 20 times magnification.
      Fractures were classified as either adhesive or cohesive or mixed. RESULTS: The
      highest ultimate shear strength observed for composite-composite associations was
      found for the groups: Z/Z, C/S, H/H, H/S, Z/S and C/C. Those associations
      containing the Durafill resin were weaker than the others. CONCLUSION:
      Microparticle RBC associations presented lower shear strength than hybrid and/or
      nanoparticle RBC associations, once the only significant difference was found
      when the Durafill resin was involved.

PMID- 18336986
TI  - Marginal leakage in direct and indirect composite resin restorations in primary
      teeth: an in vitro study.
AB  - OBJECTIVE: The aim of this study was to evaluate the marginal leakage in class II
      preparations, with margins in enamel, restored with composite resin indirect and
      direct restorations. METHODS: Twenty extracted primary molars were chosen and
      divided at random into two groups: G1 (n=10) restored by a direct technique and
      G2 (n=10) restored by an indirect technique. The composite resin Filtek Z250 (3M)
      and the Adper Single Bond adhesive (3M) were used in both groups. Teeth were
      stored in a humid environment at 37 degrees C for 1 week, thermo cycled (500
      cycles, 5 degrees C and 55 degrees C), sealed and immersed in a 0.5% basic
      fuchsine dye for 24h. Teeth were longitudinally sectioned, in a mesio-distal
      direction and leakage was assessed. RESULTS: No leakage in the specimens from G2
      and leakage in four specimens from G1, but the Mann-Whitney test showed that
      there was no statistically significant difference between the groups, either for
      occlusal box (p=0.317) and proximal box (p=0.067). CONCLUSION: This study
      demonstrated that direct and indirect class II composite resin restorations with
      cervical margins in enamel show similar results regarding marginal leakage.

PMID- 18336987
TI  - Dental students' knowledge of human immunodeficiency virus.
AB  - OBJECTIVE: This study evaluated final year dental students' knowledge of human
      immunodeficiency virus (HIV), lesions associated with HIV, potential transmission
      routes of HIV, and their perception of the teaching received on cross-infection
      precautions, virology, sterilization practice and procedure, barrier dentistry
      and recognition of blood-borne virus risk group. METHODOLOGY: Structured
      questionnaires on knowledge of human immunodeficiency virus were filled by final
      year dental students of University of Lagos, Nigeria. A total of 35 out of 37
      questionnaires were returned filled giving a response rate of 94.6%. RESULTS:
      Most of the students rated the teaching they received on cross-infection
      precautions, sterilization practice and procedure, as adequate. More than a
      quarter (28.5%) of the students rated the teaching they received on virology and
      recognition of blood-borne virus risk group to be less than adequate. Most of the
      students were able to recognize the association of oral Kaposi sarcoma, oral
      candidiasis, oral hairy leukoplakia, and salivary gland enlargement with HIV
      infection. There was a much lower level of knowledge of oral melanotic
      hyperpigmentation and idiopathic thrombocytopaenic pupura. Their knowledge of HIV
      and its potential transmission routes were adequate. CONCLUSION: This study
      revealed that final year dental students of the University of Lagos in
      southwestern region of Nigeria had adequate knowledge of routes of transmission
      of HIV in clinical practice. However, there is need for improvement in teaching
      of the students on virology and recognition of blood-borne virus risk group.

PMID- 18336988
TI  - Peritoneal fluid flow influences anatomical distribution of endometriotic
      lesions: why Sampson seems to be right.
AB  - Endometriosis is a frequent pathology for which the dominant signs and symptoms
      are pelvic pain and infertility. The physiopathology remains the subject of
      controversy. Four physiopathological hypotheses have been put forward:
      regurgitation, metaplasia, induction and (vascular and lymphatic) embolization.
      The anatomical distribution of endometriotic lesions would appear to be
      fundamental for a better understanding of Sampson's menstrual regurgitation
      theory of endometriosis. Analysis of the results in the literature and comparison
      with our experience clearly shows that the distribution of endometriotic lesions
      is asymmetrical in several respects. Abdominopelvic anatomy and peritoneal fluid
      flow can explain this asymmetrical distribution of endometriotic lesions in the
      great majority of cases. These observations are a very strong argument in favour
      of the crucial role played by tubal regurgitation and the peritoneal fluid in the
      physiopathology of endometriosis. The similarity in anatomical distribution of
      endometriomas, superficial and deeply invasive endometriotic lesions would tend
      to indicate a common origin for these different types of lesions.

PMID- 18336989
TI  - Economic assessment of managing processionary moth in pine forests: a case-study
      in Portugal.
AB  - This paper assesses the private and social profitability of current strategies
      for managing processionary moth (Thaumetopoea pityocampa) in Portuguese pine
      forests, looking at economic and environmental costs and benefits. Costs include
      the expenses for forest treatment and the social costs of threats to human health
      (dermatitis amongst others); benefits are assessed in terms of both revenue and
      social benefits such as carbon fixation and recreation. The evaluation was done
      using Cost Benefit Analysis (CBA) as an analytical framework. While this tool is
      currently applied to forest and environmental assessment and specific
      applications to pest management strategies are to be found in agricultural
      economics, rather few attempts have been made in the field of forest pest
      management. In order to assess and compare with--without options, a case-study
      was analysed for the Setubal Peninsula, south of Lisbon, an area where extensive
      stands of maritime pine (Pinus pinaster) grow. The exercise has shown that CBA
      can be a valuable tool for assessing the economic and social profitability of
      pest management. The results demonstrate that the loss of revenues in the no
      management option is not sufficient to make pest management profitable for
      private forest owners in the short-term. Conversely, a social profit is gained as
      pest management minimizes health risks for humans and avoids possible
      recreational losses.

PMID- 18336990
TI  - Electrochemical treatment of aqueous wastes containing pyrogallol by BDD-anodic
      oxidation.
AB  - In this work, the electrochemical oxidation of pyrogallol (1,2,3
      trihydroxybenzene) on boron-doped diamond anodes has been studied. The
      voltammetric results showed that pyrogallol oxidation takes place in the same
      potential region as that of phenol where the supporting electrolyte is stable.
      Synthetic wastewaters containing pyrogallol have been treated in a bench-scale
      electrolysis plant. This plant operates in a discontinuous mode by recirculating
      the waste continuously through a single-chamber electrochemical flow cell. The
      complete mineralization of pyrogallol and the electro-generated pollutants is
      obtained in the electrolytic device. HPLC analyses show the formation of
      carboxylic acids as the main intermediates. The efficiency of the electrochemical
      process was found to depend mainly on the pollutant concentration present in the
      waste and on the applied current density. The high efficiency of this technology
      can be explained in terms of the direct electro-oxidation at the BDD surface and
      the oxidation carried out by hydroxyl radicals and other electro-generated
      oxidants.

PMID- 18336991
TI  - Tissue pulsatility imaging of cerebral vasoreactivity during hyperventilation.
AB  - Tissue pulsatility imaging (TPI) is an ultrasonic technique that is being
      developed at the University of Washington to measure tissue displacement or
      strain as a result of blood flow over the cardiac and respiratory cycles. This
      technique is based in principle on plethysmography, an older nonultrasound
      technology for measuring expansion of a whole limb or body part due to perfusion.
      TPI adapts tissue Doppler signal processing methods to measure the
      "plethysmographic" signal from hundreds or thousands of sample volumes in an
      ultrasound image plane. This paper presents a feasibility study to determine if
      TPI can be used to assess cerebral vasoreactivity. Ultrasound data were collected
      transcranially through the temporal acoustic window from four subjects before,
      during and after voluntary hyperventilation. In each subject, decreases in tissue
      pulsatility during hyperventilation were observed that were statistically
      correlated with the subject's end-tidal CO2 measurements. (

PMID- 18336992
TI  - Latest technologic and surgical developments in using InterStim Therapy for
      sacral neuromodulation: impact on treatment success and safety.
AB  - OBJECTIVES: This article accompanies a "surgery in motion" DVD on sacral
      neuromodulation (SNM) with InterStim Therapy, which visualizes the implantation
      of the InterStim II system. The article describes the technical and surgical
      developments of SNM and their impact on treatment success, safety, and patient's
      quality of life (QoL). METHODS: Relevant literature on SNM with regard to
      technical changes and related clinical outcomes has been reviewed. RESULTS: Since
      its introduction in the early 1990s, SNM has proven useful in the treatment of
      several types of chronic urinary (and bowel) dysfunction. Recent technical
      improvements in devices and, in particular, the introduction of the tined lead 5
      yr ago made SNM progress from an elaborate, open-surgery, general anesthesia, one
      stage implant procedure to a minimally invasive, local anesthesia, percutaneous
      technique in two stages. The permanent tined lead implant enables a longer
      patient testing period (minimum of 14 d recommended) and less lead migration.
      This has considerably reduced technical failures and improved the success rate of
      the test phase; the response rate was almost doubled to approximately 80%. These
      improvements also affected tolerability, resulting in increased QoL for the
      patient. The use of the recently introduced smaller implantable neurostimulator
      InterStim II seems to further improve patient comfort and makes the implant
      procedure for the physician easier and shorter. However, this must be further
      addressed in clinical studies. CONCLUSIONS: SNM with InterStim Therapy using the
      tined lead offers an efficient treatment modality for patients in whom
      conservative treatment has failed.

PMID- 18336993
TI  - Reflections on 'plant neurobiology'.
AB  - Plant neurobiology, a new and developing area in the plant sciences, is a meeting
      place for scientists concerned with exploring how plants perceive signs within
      their environment and convert them into internal electro-chemical ('plant
      neurobiological') signals. These signals, in turn, permit rapid modifications of
      physiology and development that help plants adjust to changes in their
      environment. The use of the epithet 'neurobiology' in the context of plant life
      has, however, led to misunderstanding about the aims, content, and scope of this
      topic. This difficulty is possibly due to the terminology used, since this is
      often unfamiliar in the context of plants. In the present article, the scope of
      plant neurobiology is explored and some of analogical and metaphorical aspects of
      the subject are discussed. One approach to reconciling possible problems of using
      the term 'plant neurobiology' and, at the same time, of analysing information
      transfer in plants and the developmental processes which are regulated thereby,
      is through Living Systems Theory (LST). This theory specifically directs
      attention to the means by which information is gathered and processed, and then
      dispersed throughout the hierarchy of organisational levels of the plant body.
      Attempts to identify the plant 'neural' structures point to the involvement of
      the vascular tissue - xylem and phloem - in conveying electrical impulses
      generated in zones of special sensitivity to receptive locations throughout the
      plant in response to mild stress. Vascular tissue therefore corresponds, at the
      level of organismic organisation, with the informational 'channel and net'
      subsystem of LST.

PMID- 18336994
TI  - Partial cloning of CB1 cDNA and CB1 mRNA changes in stress responses in the Solea
      solea.
AB  - Endogenous cannabinoids, through the CB1 receptor, are involved in the control of
      several functions including stress responses. The aim of this study was to
      investigate the presence of cannabinoid receptor CB1 in the sole ovary by partial
      cloning of brain CB1 cDNA; in a stress paradigm of disturbance by handling, which
      consisted in catching, netting and hand-sorting, changes of CB1 mRNA were related
      with those of proopiomelanocortin (POMC) mRNA; the trend and timing of stress
      responses and adaptation were monitored by measuring plasma cortisol levels. We
      characterized two forms of CB1-like receptor, termed CB1A and CB1B. The two sole
      CB1 (both 799bp) share 76% identity in their cDNAs, and the deduced amino acid
      sequences are 80% identical. The handling stress induced a sustained increase in
      plasma cortisol levels 1h after the handling began and decreased to low levels
      12h after initiation of handling, showing the same trend of ovarian POMC mRNA
      expression. In addition, while CB1A mRNA did not show any significant changes
      during handling stress, significantly lower levels of CB1B mRNA were found in
      stressed fish 1h after the beginning of handling, with CB1 expression increased
      24h after stress induction, both in the ovary and brain. It can be concluded that
      endocannabinoid system is involved in the modulation of adaptive responses to
      environmental conditions.

PMID- 18336995
TI  - T3-mediated expression of PGC-1alpha via a far upstream located thyroid hormone
      response element.
AB  - Thyroid hormone (T3) has a profound influence on normal development,
      differentiation and metabolism. T3 induces complex gene expression patterns
      raises the question of how these expression patterns might be regulated. Since
      the transcriptional coactivator peroxisome proliferator-activated receptor gamma
      coactivator-1alpha (PGC-1alpha) induces very similar cellular energy metabolic
      pathways, we investigated the molecular mechanism of T3 regulation of PGC-1alpha.
      PGC-1alpha is rapidly regulated by T3, both in vivo and in cell culture.
      Transient transfection experiments demonstrated binding of the thyroid hormone
      receptor (TR) to a response element located at -4kb upstream of the
      transcriptional start site within the PGC-1alpha gene. Introducing of a single
      copy of the -4kb TRE in a heterologous promoter context is sufficient to maintain
      T3 responsiveness. Chromatin immunoprecipitation analysis revealed increased
      histone acetylation upon stimulation of T3. Finally, TR binds the -4kb TRE in
      electrophoretic mobility shift assays, identifying PGC-1alpha as a direct target
      of TR action. Since T3 directly regulates PGC-1alpha and PGC-1alpha coactivates
      liganded TR, we suggest an autoregulatory feed-forward loop of PGC-1alpha
      activation upon T3 treatment.

PMID- 18336996
TI  - Signaling via CNS cannabinoid receptors.
AB  - Because of the prominent psychoactive effects of cannabis and its preparations,
      much research has focused on the actions of cannabinoids, the primary
      psychoactive components of cannabis, on neuronal function. A convergence of
      research has identified (1) cannabinoid receptors, (2) endogenous compounds that
      activate these receptors (endocannabinoids), and (3) drugs that interact with
      these receptors and the proteins that synthesize and degrade the
      endocannabinoids. This review will first consider how endogenous cannabinoids
      signal through cannabinoid receptors and the various forms of synaptic plasticity
      mediated by endocannabinoids. Next the interactions between exogenous
      cannabinoids such as Delta9-tetrahydrocannabinol and endocannabinoids and
      endocannabinoid-mediated plasticity will be examined. Finally, a model will be
      presented that can explain the prominent psychoactivity of these plant-derived
      cannabinoids.

PMID- 18336997
TI  - The -149C>T SNP within the DeltaDNMT3B gene, is not associated with early disease
      onset in hereditary non-polyposis colorectal cancer.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominantly
      inherited syndrome caused by germline mutations in mismatch repair (MMR) genes.
      HNPCC patients have a lifetime risk of 80% of developing colorectal cancer (CRC);
      however the likely age of onset is difficult to predict. A single C>T
      polymorphism located within the promoter region of the DeltaDNMT3B gene has
      recently been reported to be associated with a significant increase to the risk
      of early onset CRC. In this study we determined the DeltaDNMT3B genotype in 404
      confirmed HNPCC participants (total of 194 CRC cases) from Australia (203) and
      Poland (201). From the total number of participants there were 194 diagnosed
      cases of CRC and 210 healthy MMR gene mutation carriers. The study was undertaken
      to assess whether the reported effect observed in a previous study of 146 HNPCC
      patients is consistent in a larger separate and unrelated participant cohort.
      Through the statistical tests of Kaplan-Meier survival analysis and Cox hazard
      regression models we did not observe any significant association between the
      DeltaDNMT3B C>T SNP and early onset CRC in HNPCC patients.

PMID- 18336998
TI  - Thermal behavior, specific heat capacity and adiabatic time-to-explosion of G(FOX
      7).
AB  - [H(2)N=C(NH(2))(2)](+)(FOX-7)(-)-G(FOX-7) was prepared by mixing FOX-7 and
      guanidinium chloride solution in potassium hydroxide solution. Its thermal
      decomposition was studied under the non-isothermal conditions with DSC and TG/DTG
      methods. The apparent activation energy (E) and pre-exponential constant (A) of
      the two exothermic decomposition stages were obtained by Kissinger's method and
      Ozawa's method, respectively. The critical temperature of thermal explosion
      (T(b)) was obtained as 201.72 degrees C. The specific heat capacity of G(FOX-7)
      was determined with Micro-DSC method and theoretical calculation method and the
      standard molar specific heat capacity is 282.025 J mol(-1) K(-1) at 298.15 K.
      Adiabatic time-to-explosion of G(FOX-7) was also calculated to be a certain value
      between 13.95 and 15.66 s.

PMID- 18336999
TI  - Influence of ozone concentration and temperature on ultra-fine particle and
      gaseous volatile organic compound formations generated during the ozone-initiated
      reactions with emitted terpenes from a car air freshener.
AB  - Experiments were conducted to identify the emissions from the car air freshener
      and to identify the formation of ultra-fine particles and secondary gaseous
      compounds during the ozone-initiated oxidations with emitted volatile organic
      compounds (VOCs). The identified primary constituents emitted from the car air
      freshener in this study were alpha-pinene, beta-pinene, p-cymene, and limonene.
      Formation of ultra-fine particles (4.4-160 nm) was observed when ozone was
      injected into the chamber containing emitted monoterpenes from the air freshener.
      Particle number concentrations, particle mass concentrations, and surface
      concentrations were measured in time dependent experiments to describe the
      particle formation and growth within the chamber. The irritating secondary
      gaseous products formed during the ozone-initiated reactions include
      formaldehyde, acetaldehyde, acrolein, acetone, and propionaldehyde. Ozone
      concentration (50 and 100 ppb) and temperature (30 and 40 degrees C)
      significantly affect the formation of particles and gaseous products during the
      ozone-initiated reactions. The results obtained in this study provided an insight
      on the potential exposure of particles and irritating secondary products formed
      during the ozone-initiated reaction to passengers in confined spaces.

PMID- 18337000
TI  - Characterization of the biosorption of cadmium, lead and copper with the brown
      alga Fucus vesiculosus.
AB  - The recovery of cadmium, lead and copper with the brown alga Fucus vesiculosus
      was characterized and quantified. The biosorption data fitted the pseudo-second
      order and Langmuir isotherm models, but did not adjust to the intraparticle
      diffusion model. The metal uptakes deduced from the pseudo-second order kinetic
      model and the Langmuir isotherm model followed a similar sequence: Cu>Cd
      approximately Pb. The Langmuir maximum metal uptakes were: 0.9626 mmol/g, Pb 1.02
      mmol/g, and Cu 1.66 mmol/g. According to the equilibrium constants of this
      isotherm model, the affinity of metals for the biomass followed this order:
      Pb>Cu>Cd. Biosorption was accomplished by ion exchange between metals in solution
      and algal protons, calcium and other light metals, and by complexation of the
      adsorbed metals with algal carboxyl groups. FTIR spectra showed a shift in the
      bands of carboxyl, hydroxyl and sulfonate groups.

PMID- 18337001
TI  - Air distribution and size changes in the remediated zone after air sparging for
      soil particle movement.
AB  - In an unconsolidated porous medium, soil particles can be mobilized by physical
      perturbation. In model systems of fluids flowing over spherical particles
      attached to flat surfaces, the hydrodynamic shear force depends on the fluid
      viscosity, particle radius, and flow velocity. Soil particles can be reasonably
      expected to be transported by flowing water during air sparging when the particle
      size distribution does not fit the densest possible particle arrangement. If soil
      particles are transported during air sparging, then the distribution of the
      porosity and reservoir permeability will change. The remediated zone changes
      because of the changes in soil characteristics. This study applied some
      mathematical models to elucidate the mobilization process of soil particles
      during in situ air sparging. The changes in the characteristics of the soil and
      the swept volume of injected air during air sparging were also investigated. The
      results demonstrated that particle movement reduced the radius of influence (ROI)
      and the swept volume of injected air. In this case study, the maximum reducing
      rates in ROI and the swept volume were 24% and 26% for the zone where the gas
      saturation exceeded 10%.

PMID- 18337002
TI  - Hazardous waste management in Chilean main industry: an overview.
AB  - The new "Hazardous Waste Management Regulation" was published in the Official
      Newspaper of the Chilean Republic on 12 June 2003, being in force 365 days after
      its publication (i.e., 12 June 2004). During the next 180 days after its
      publication (i.e., until 12 December 2004), each industrial facility was
      obligated to present a "Hazardous Waste Management Plan" if the facility
      generates more than 12 ton/year hazardous wastes or more than 12 kg/year acute
      toxic wastes. Based on the Chilean industrial figures and this new regulation,
      hazardous waste management plans were carried out in three facilities of the most
      important sectors of Chilean industrial activity: a paper production plant, a Zn
      and Pb mine and a sawmill and wood remanufacturing facility. Hazardous wastes
      were identified, classified and quantified in all facilities. Used oil and oil
      contaminated materials were determined to be the most important hazardous wastes
      generated. Minimization measures were implemented and re-use and recycling
      options were analyzed. The use of used oil as alternative fuel in high energy
      demanding facilities (i.e., cement facilities) and the re-refining of the used
      oil were found to be the most suitable options. In the Zn and Pb mine facility,
      the most important measure was the beginning of the study for using spent oils as
      raw material for the production of the explosives used for metals recovery from
      the rock. In Chile, there are three facilities producing alternative fuels from
      used oil, while two plants are nowadays re-refining oil to recycle it as
      hydraulic fluid in industry. In this sense, a proper and sustainable management
      of the used oil appears to be promissory.

PMID- 18337003
TI  - Re-activation of atrophic motor Schwann cells after hypoglossal-facial nerve
      anastomosis.
AB  - Facial nerve lesions are common in humans and often require surgical
      intervention. If repair is delayed, reinnervation can be facilitated by
      transposing the freshly cut hypoglossal nerve end-to-end directly to the distal
      facial nerve, allowing for uncompromised hypoglossal axons to reinnervate the
      denervated facial musculature (hypoglossal-facial anastomosis, HFA). Schwann
      cells (SCs) in the distal nerve stump have an important function in promoting
      axonal regeneration by expressing multiple regeneration-associated proteins.
      Chronically denervated SCs cease to express those factors, but it is unknown
      whether they can be reactivated by fresh axonal sprouts and regain part of their
      function. We evaluated SC function and viability in distal facial nerve stump of
      rats at various time points after chronic denervation as well as following
      immediate or delayed HFA by assessing their expression of growth-associated
      protein 43 kDa (GAP-43) and the neuregulin receptors erbB2 and erbB4. Our results
      show that maximal upregulation of those factors in denervated SCs occurred a few
      weeks after nerve transection, indicating that a short period of denervation
      might even be beneficial before nerve repair. Motor SCs denervated for 32 weeks
      had downregulated their activity and ceased to express the regeneration
      associated factors. SCs immediately re-expressed GAP-43, erbB2, and erbB4
      following contact with fresh hypoglossal motor axons, demonstrating they are
      competent to promote regeneration even after long-term denervation.

PMID- 18337004
TI  - Ablation of antennae does not disrupt magnetoreceptive behavioural reaction of
      the American cockroach to periodically rotated geomagnetic field.
AB  - Neither a mode of function nor an exact anatomical localisation of the animal
      magnetoreceptor have been identified in any organism. Insects' antennae are
      organs specialized as unique neural input structures for a number of sensory
      modalities and have also been suggested to play a certain role in
      magnetoreception. In the present study, we used the American cockroach
      Periplaneta americana and tested the impact of amputation of both its antennae on
      the spontaneous magnetosensitive behaviour. By means of a full-laboratory assay
      we registered a non-specific unlearned movement reaction to the changing magnetic
      environment within the frame of the natural time and intensity parameters of the
      field. We report no loss of the magnetoreceptive behaviour in antennaeless
      cockroaches. Our finding narrows the spectrum of the insects' magnetite-rich
      nerve structures which might potentially be involved in magnetoreception.

PMID- 18337005
TI  - The influence of postural threat on the cortical response to unpredictable and
      predictable postural perturbations.
AB  - This study investigated the effects of postural threat on the cortical response
      associated with postural reactions to predictable and unpredictable perturbations
      to upright stance. Postural threat was manipulated by having individuals stand on
      an elevated surface to alter the context in which the postural task was
      performed. Ten healthy young adults experienced a series of predictable and
      unpredictable trunk perturbations when standing at ground level and at the edge
      of a platform located 3.2 m above the ground. Participants felt less confident,
      more fearful of falling, more anxious and less stable when standing at the high
      surface height. Unpredictable perturbations generated a large negative potential
      (N1) which was increased by 84% when standing at the high compared to low surface
      height. The magnitude of change in this potential was related to the magnitude of
      change in balance perceptions, such as confidence and fear. Predictable
      perturbations did not generate a N1 potential but instead produced an
      anticipation-related potential prior to the perturbation. This cortical activity
      observed in response to predictable perturbations was not influenced by postural
      threat. A large N1 potential was observed for a 'surprise' perturbation that
      followed a series of predictable perturbations. There was a trend for the
      amplitude of this potential to be increased when standing at the high compared to
      low surface height. The results of this study provide evidence for the modulating
      influence of psychological factors related to postural threat on the cortical
      activity associated with postural reactions to unpredictable perturbations.

PMID- 18337006
TI  - What are the factors responsible for the deviation in stepping on the spot?
AB  - Without vision, keeping a straight-ahead direction while stepping on the spot is
      almost impossible, everybody deviates more or less. Several explanations for
      this, such as laterality, vestibulo-spinal influence, dopamine system, have been
      proposed. The aims of the experiment presented here were (1) to quantify the
      lateral deviation when stepping using a modified Fukuda test apparatus, and (2)
      to determine the factors potentially underlying such deviation. Twenty-five young
      adults, blindfolded, performed the experiment which consisted in stepping while
      holding a rotating vertical roll bar fixed on the wall. Four experimental
      conditions (i.e., normal, with an imposed pace, dual-task, or with the neck bent)
      were tested. All participants deviated towards one side or the other in all
      conditions. Adding an attentional load or imposing a particular pace did not
      change the amount of deviation. For three conditions (normal, with an imposed
      pace and dual-task), the deviation towards one side was not significantly larger
      than towards the other side at the group level. In the bent-neck condition, the
      deviation was significantly larger than in the other conditions. Furthermore, in
      this condition the deviation towards the left was significantly larger than the
      deviation towards the right at the group level. We discussed the results
      regarding the role of vestibular information and proprioceptive feedback from
      neck muscles in correcting a spontaneous deviation. Our results, however, go
      against the idea that sensorimotor lateral preferences are among the factors
      underlying such deviations, since we found no relationship between lateral
      preferences (hand, foot, and eye) and the side of deviation.

PMID- 18337007
TI  - Short-term modulation of the ipsilateral primary sensory cortex by nociceptive
      interference revealed by SEPs.
AB  - We studied the modulation of the topographic arrangement of the human ipsilateral
      primary somatosensory cortex following interference of nociceptive stimuli by
      means of dipole source analysis. Multichannel somatosensory evoked potentials
      were obtained by electrical stimulation of digits 1 and 5 of the left hand
      before, during and after the application of pain to digits 2-4 of the right hand.
      The primary cortical response of the SEP (N20) was obtained for dipole
      localization of the representation of the primary sensory cortex receiving input
      from digits 1 to 5. The 3D-distance between these sides was calculated for
      further analysis. To account for possible attentional effects recordings were
      performed while simultaneously to this intervention subjects were asked to turn
      their attention to the right or left hand in a pseudorandom order. The
      application of pain induced an expansion of the 3D-distance between digits 1 and
      5. Focusing attention to the stimulated limb or the site of the intervention did
      not yield to an additional effect. Our results provide further evidence for the
      presence of a quickly adapting interaction between primary somatosensory areas of
      both hemispheres following an interference of nociceptive stimulation in SEPs.
      This modifying process is probably mediated by interhemispheric and intercortical
      connections leading to hyperexcitability of the primary sensory cortex
      contralateral to that receiving nociceptive input. Spatial attention does not
      seem to have an impact on this kind of short-term intercortical plasticity.

PMID- 18337008
TI  - Pharmacological blockade of the vanilloid receptor TRPV1 elicits marked
      hyperthermia in humans.
AB  - The vanilloid receptor TRPV1 has been identified as a molecular target for the
      treatment of pain associated with inflammatory diseases and cancer. Hence, TRPV1
      antagonists have been considered for therapeutic evaluation in such diseases.
      During Phase I clinical trials with AMG 517, a highly selective TRPV1 antagonist,
      we found that TRPV1 blockade elicited marked, but reversible, and generally
      plasma concentration-dependent hyperthermia. Similar to what was observed in
      rats, dogs, and monkeys, hyperthermia was attenuated after repeated dosing of AMG
      517 (at the highest dose tested) in humans during a second Phase I trial.
      However, AMG 517 administered after molar extraction (a surgical cause of acute
      pain) elicited long-lasting hyperthermia with maximal body temperature surpassing
      40 degrees C, suggesting that TRPV1 blockade elicits undesirable hyperthermia in
      susceptible individuals. Mechanisms of AMG 517-induced hyperthermia were then
      studied in rats. AMG 517 caused hyperthermia by inducing tail skin
      vasoconstriction and increasing thermogenesis, which suggests that TRPV1
      regulates vasomotor tone and metabolic heat production. In conclusion, these
      results demonstrate that: (a) TRPV1-selective antagonists like AMG 517 cannot be
      developed for systemic use as stand alone agents for treatment of pain and other
      diseases, (b) individual susceptibility influences magnitude of hyperthermia
      observed after TRPV1 blockade, and (c) TRPV1 plays a pivotal role as a molecular
      regulator for body temperature in humans.

PMID- 18337009
TI  - Acupuncture modulates resting state connectivity in default and sensorimotor
      brain networks.
AB  - Previous studies have defined low-frequency, spatially consistent networks in
      resting fMRI data which may reflect functional connectivity. We sought to explore
      how a complex somatosensory stimulation, acupuncture, influences intrinsic
      connectivity in two of these networks: the default mode network (DMN) and
      sensorimotor network (SMN). We analyzed resting fMRI data taken before and after
      verum and sham acupuncture. Electrocardiography data were used to infer autonomic
      modulation through measures of heart rate variability (HRV). Probabilistic
      independent component analysis was used to separate resting fMRI data into DMN
      and SMN components. Following verum, but not sham, acupuncture there was
      increased DMN connectivity with pain (anterior cingulate cortex (ACC),
      periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal
      formation, middle temporal gyrus) related brain regions. Furthermore, increased
      DMN connectivity with the hippocampal formation, a region known to support memory
      and interconnected with autonomic brain regions, was negatively correlated with
      acupuncture-induced increase in a sympathetic related HRV metric (LFu), and
      positively correlated with a parasympathetic related metric (HFu). Following
      verum, but not sham, acupuncture there was also increased SMN connectivity with
      pain-related brain regions (ACC, cerebellum). We attribute differences between
      verum and sham acupuncture to more varied and stronger sensations evoked by verum
      acupuncture. Our results demonstrate for the first time that acupuncture can
      enhance the post-stimulation spatial extent of resting brain networks to include
      anti-nociceptive, memory, and affective brain regions. This modulation and
      sympathovagal response may relate to acupuncture analgesia and other potential
      therapeutic effects.

PMID- 18337010
TI  - An improved in situ measurement of offset phase shift towards quantitative
      damping-measurement with AFM.
AB  - An improved approach is introduced in damping measurement with atomic force
      microscope (AFM) for the in situ measurement of the offset phase shift needed for
      determining the intrinsic mechanical damping in nanoscale materials. The offset
      phase shift is defined and measured at a point of zero contact force according to
      the deflection part of the AFM force plot. It is shown that such defined offset
      phase shift is independent of the type of sample material, varied from hard to
      relatively soft materials in this study. This improved approach allows the self
      calibrated and quantitative damping measurement with AFM. The ability of dynamic
      mechanical analysis for the measurement of damping in isolated one-dimensional
      nanostructures, e.g. individual multiwalled carbon nanotubes, was demonstrated.

PMID- 18337011
TI  - Dehydroepiandrosterone increases resistance to experimental infection by
      Trypanosoma cruzi.
AB  - Dehydroepiandrosterone (DHEA) enhances immune responses against a wide range of
      viral, bacterial, and parasitic pathogens. In a previous study, we reported that
      administration of DHEA significantly decreased the numbers of blood parasites in
      Trypanosoma cruzi experimental infection. The present study was undertaken to
      determine the effectiveness of DHEA in reducing the severity of acute phase T.
      cruzi infection of male and female Wistar rats. Animals were treated
      subcutaneously with 40 mg/kg body weight/day of DHEA. The concentration of nitric
      oxide (NO) was determined in spleen peritoneal cavity. Interleukin-2 (IL-2) and
      interferon-gamma (IFN-gamma) were determined in the sera of uninfected and
      infected animals. DHEA treatment augments NO production for both sexes after in
      vitro LPS treatment for uninfected animals. Infection triggered enhanced NO
      levels although not significant. IL-2 and IFN-gamma were detectable in higher
      concentrations in treated and infected rats of both genders when compared to
      untreated controls. These data suggest that DHEA may have a potent
      immunoregulatory function that can affect the course of T. cruzi infection.

PMID- 18337012
TI  - Efficacy of different treatment regimens of marbofloxacin in canine visceral
      leishmaniosis: a pilot study.
AB  - This phase II, randomized, open-label field trial was designed to evaluate and
      compare the safety and efficacy of four treatment durations (10, 20, 28 or 40
      days) with marbofloxacin administered orally at the dosage of 2mg/kg once a day
      for canine visceral leishmaniosis. Twenty-four dogs naturally infected with
      visceral leishmaniosis and without biochemical disorder evidences of renal
      insufficiency, were recruited by two Greek veterinarian clinics. They were also
      randomly assigned to one of the four treatment duration groups, and have been
      clinically, haematologically, biochemically and parasitologically followed-up
      regularly for 9 months. Efficacy was achieved for 5/6 dogs treated for 28 days,
      4/6 dogs treated for 10 or 20 days and for 3/6 dogs treated for 40 days.
      Moreover, efficacy was reached more quickly (58.4 days) in dogs treated for 28
      days. Improvement of clinical signs tended to be better and faster in the 28 days
      treatment group too. After 9 months of follow-up, a total of three cases could be
      considered as relapsing (two dogs treated for 40 days and one dog treated for 28
      days). There was a significant reduction in amastigotes density in macrophages
      after 3 months in the four groups when compared with the parasite density at
      inclusion. No adverse effects were noticed during this 9 months study. Results
      obtained with marbofloxacin at the dosage of 2mg/kg once a day for 28 days seem
      encouraging and may offer a safe alternative for treating canine visceral
      leishmaniosis.

PMID- 18337013
TI  - Vaccination against Haemonchus contortus: performance of native parasite gut
      membrane glycoproteins in Merino lambs grazing contaminated pasture.
AB  - In a replicated trial, parasitological and antibody responses of grazing weaner
      Merino sheep were assessed following vaccination with gut membrane proteins
      prepared from adult worms of the gastrointestinal nematode, Haemonchus contortus.
      Each vaccinated animal received 100 microg native H11 and 100 microg native H-gal
      GP combined together in 5mg Quil A administered intramuscularly on days 0, 34, 80
      and 127. Control animals received 5mg Quil A alone on the same days. Vaccinated
      and unvaccinated control animals grazed pastures contaminated with the parasite
      from day 34 of the trial, and levels of parasitism were monitored by worm-egg
      counts (WECs) in faeces and packed cell volumes (PCVs) in blood. The level of
      larval contamination on pasture was estimated from the worm counts of tracer
      sheep introduced monthly to the paddocks. WECs and anaemia were significantly
      reduced in vaccinated animals, and, in contrast to vaccinates, all control sheep
      required salvage treatment with anthelmintic. By the last 2 months of the trial,
      pastures grazed by vaccinated animals had significantly lower contamination with
      H. contortus larvae. Vaccinated animals had high levels of vaccine antigen
      specific IgG1 and IgG2 antibodies in plasma, whereas those responses in the
      control sheep were very low. IgG1 titres in the vaccinated group, but not IgG2
      titres, were inversely correlated with worm-egg counts. The levels of systemic
      IgA and IgE remained low but increased in both groups towards the end of the
      experiment most probably from exposure to the natural infection from pasture. The
      results showed that H11 and H-gal-GP behaved like "hidden" antigens producing
      high levels of protection that were probably mediated through mechanisms
      involving antibodies, and in particular, IgG1. It was concluded that if similar
      protective effects could be obtained with recombinant versions of the proteins
      present in either H11 or H-gal-GP, then the prospects for a commercial Haemonchus
      vaccine were real.

PMID- 18337014
TI  - Haemonchus contortus infection in sheep: parasite fecundity correlates with worm
      size and host lymphocyte counts.
AB  - Two experiments were conducted to elucidate the timing and nature of the sheep
      immune response to Haemonchus contortus (Barber's pole worm). The first
      experiment examined the establishment of H. contortus populations and the immune
      response by comparing a bolus infection of third-stage larvae in naive sheep with
      a group previously primed by a trickle infection. The second experiment used
      staggered doses of ivermectin-resistant larvae to compare the development of
      adult worms during different durations of trickle infection with ivermectin
      sensitive larvae. Infections successfully generated pathological signs of
      haemonchosis such as anaemia. Image analysis software was used to measure the
      area and perimeter of worms collected at post-mortem, and the number of eggs
      present in individual adult females (fecundity) was significantly correlated with
      worm size. A significant inverse correlation was found between blood lymphocyte
      counts and worm fecundity. The absence of correlation between worm fecundity and
      other leukocyte and erythrocyte counts highlighted the specificity of the
      lymphocyte response. This is the first report of a link between haematology
      profiles and worm fecundity in haemonchosis. The correlation observed between
      adult worm size and egg content leads to the hypothesis that egg production in H.
      contortus is limited by immune regulation of worm size and presumably growth.
      Mean worm size and fecundity declined as sheep received more prolonged trickle
      infections before necropsy, confirming previous reports that immune responses to
      adult worms are enhanced by ongoing larval challenge. Immunohistochemical results
      showed trends consistent with a Th2 (humoral) immune response which has been
      implicated in reducing nematode burdens in several species.

PMID- 18337015
TI  - Risk factors associated with Tritrichomonas foetus infection in beef herds in the
      Province of Buenos Aires, Argentina.
AB  - Bovine trichomonosis (BT) is a contagious disease, characterized by reproductive
      failure, embryonic losses, infertility, and abortions, which directly impacts the
      reproductive performance of cattle. In this cross-sectional questionnaire-based
      study, 56 veterinarians provided information on the geographic location and on
      the demographic, husbandry, and sanitary characteristics of 173 beef herds
      located in 26 (21%) counties of the Province of Buenos Aires, Argentina. Herds
      rearing beef cattle (OR=2.5, 95% CI=1.0, 6.3), with low pregnancy rate in cows
      (<or=90%) (OR=4.1, 95% CI=1.5, 10.8), sharing livestock with other owners or
      farmers (OR=5.4, 95% CI=1.8, 16.5), and where trichomonosis was reported during
      the previous year (OR=4.1, 95% CI=1.7, 9.6) were at significantly greater risk of
      being BT positive. This study provided information for future risk assessment
      and/or management plans for the prevention and control of BT in a region where
      the disease is considered to be endemic.

PMID- 18337017
TI  - Effectiveness of the CAGE questionnaire, gamma-glutamyltransferase and mean
      corpuscular volume of red blood cells as markers for alcohol-related problems in
      the workplace.
AB  - OBJECTIVE: To evaluate the usefulness of gamma-glutamyltransferase (GGT) and mean
      corpuscular volume (MCV), as well as that of the CAGE questionnaire, in workplace
      screening for alcohol abuse/dependence. METHODS: A total of 183 male employees
      were submitted to structured interviews (Structured Clinical Interview for DSM-IV
      2.0 and CAGE questionnaire). Blood samples were collected. Diagnostic accuracy
      and odds ratio were determined for the CAGE, GGT and MCV. RESULTS: The CAGE
      questionnaire presented the best sensitivity for alcohol dependence (91%;
      specificity, 87.8%) and for alcohol abuse (87.5%, specificity, 80.9%), which
      increased when the questionnaire was used in combination with GGT (sensitivity,
      100% and 87.5%, respectively; specificity, 68% and 61.5, respectively). CAGE
      positive results and/or alterations in GGT were less likely to occur among
      employees not presenting alcohol abuse/dependence than among those presenting
      such abuse (OR for CAGE=13, p<0.05; OR for CAGE-GGT=11, p<0.05) or dependence (OR
      for CAGE=76, p<0.01; OR for GGT=5, p<0.01). Employees not presenting alcohol
      abuse/dependence were also several times more likely to present negative CAGE or
      GGT results. CONCLUSIONS: The use short, simple questionnaires, combined with
      that of low-cost biochemical markers, such as GGT, can serve as an initial
      screening for alcohol-related problems, especially for employees in hazardous
      occupations. The data provided can serve to corroborate clinical findings.

PMID- 18337016
TI  - Glucose metabolic changes in the prefrontal cortex are associated with HPA axis
      response to a psychosocial stressor.
AB  - The prefrontal cortex (PFC) has been well known for its role in higher order
      cognition, affect regulation and social reasoning. Although the precise
      underpinnings have not been sufficiently described, increasing evidence also
      supports a prefrontal involvement in the regulation of the hypothalamus-pituitary
      adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation
      during a psychosocial stress exposure in 14 healthy humans. Regional brain
      metabolism was assessed using positron emission tomography (PET) and injection of
      fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC,
      increased glucose metabolic rate was associated with lower or higher salivary
      cortisol concentration in response to a psychosocial stress condition. Metabolic
      glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was
      negatively associated with stress-induced salivary cortisol increases.
      Furthermore, metabolic glucose rate in these regions was inversely coupled with
      changes in glucose metabolic rate in other areas, known to be involved in HPA
      axis regulation such as the amygdala/hippocampal region. In contrast, metabolic
      glucose rate in areas more lateral to the mPFC was positively associated with
      saliva cortisol. Subjective ratings on task stressfulness, task controllability
      and self-reported dispositional mood states also showed positive and negative
      associations with the glucose metabolic rate in prefrontal regions. These
      findings suggest that in humans, the PFC is activated in response to psychosocial
      stress and distinct prefrontal metabolic glucose patterns are linked to endocrine
      stress measures as well as subjective ratings on task stressfulness,
      controllability as well as dispositional mood states.

PMID- 18337018
TI  - CD117 expression in normal, neoplastic, inflammatory, and reactive lesions of the
      thyroid.
AB  - The mutations of c-kit gene, which encodes a transmembrane receptor tyrosine
      kinase (CD117-KIT) or activation of CD117, lead to the activation of signal
      transduction cascades regulating cell proliferation, apoptosis, chemotaxis, and
      adhesion. The aim of this study was to investigate the expression of CD117 in
      normal, inflammatory, neoplastic, and reactive lesions of the thyroid. Using
      polyclonal anti-CD117 antibody, we performed immunohistochemical staining on
      tissue blocks from 230 cases obtained from the archives of the Department of
      Pathology, Ondokuz Mayis University (Samsun, Turkey), collected between 1990 and
      2006. Each slide was evaluated for extent and intensity of staining. Staining
      extent was expressed as the percentage of stained cells. Staining of <10% of the
      cells was accepted as negative. Staining intensity was evaluated only in positive
      cases. By addition of the extent and intensity scores, the combined score was
      calculated. In our study, the combined CD117 staining scores of neoplastic and
      inflammatory groups were found to be higher than the reactive and normal groups.
      Within the neoplastic group, papillary carcinomas differed from follicular
      adenomas significantly, although papillary carcinomas showed no statistically
      significant difference compared to follicular carcinomas. Immunohistochemical
      CD117 positivity was detected in a wide range of neoplastic and inflammatory
      thyroid diseases. The neoplastic group and, within them, the papillary carcinomas
      showed a higher ratio of CD117 positivity. Although our results need to be
      confirmed by other molecular and genetic studies, the high rate of positivity in
      papillary carcinomas was one of the striking findings, which may result in novel
      diagnostic and therapeutic approaches.

PMID- 18337019
TI  - Molecular genetic analysis of surveillance biopsy samples from Barrett's mucosa-
      significance of sampling.
AB  - Our aim was to determine the spectrum and accumulation of mutations in
      surveillance biopsies from Barrett's mucosa of individual patients during follow
      up. We performed loss of heterozygosity (LOH) analysis of six recently described
      tumor suppressor genes relevant for the carcinogenesis of Barrett's
      adenocarcinoma from laser-microdissected, paraffin-embedded biopsy samples of
      Barrett's mucosa without or with low-grade dysplastic change. 118 biopsy samples
      from 26 patients were taken during surveillance programs in time intervals
      ranging between 6 and 51 months. We found no significant increase in LOH events
      at least in a 51-month interval. In two patients, Barrett's adenocarcinoma was
      diagnosed 6 months after the first diagnosis of Barrett's mucosa. Six of 26
      patients did not show LOH. The remaining patients exhibited a striking variation
      of LOH patterns and accumulations in biopsy samples during follow-up. From our
      microsatellite marker panel, we were not able to define a single surrogate marker
      that could serve as a potential biomarker, indicating an increased risk of
      progression to Barrett's adenocarcinoma. However, LOH combinations, especially
      APC/p16(INK4) or APC/p53, deserve attention as putative biomarkers in future
      studies. Our results raise important questions regarding the biological dynamics
      of mutations in Barrett's mucosa in addition to the influence of sampling,
      especially with regard to the number of biopsies taken from Barrett's mucosa.

PMID- 18337020
TI  - Lymphocyte sub-populations and non-Langerhans' cell monocytoid cells in pulmonary
      Langerhans' cell histiocytosis.
AB  - Pulmonary Langerhans' cell histiocytosis (PLCH) is a disease characterized by the
      occurrence of complex fibro-cellular interstitial lesions dominated by
      Langerhans' cells (LC), which occurs predominantly in young adult smokers. We
      undertook this retrospective study to better define the lymphohistiocytic cell
      populations in PLCH in order to obtain a greater insight into its pathogenesis.
      Formalin-fixed, paraffin-embedded, surgically excised, archival lung tissue from
      seven patients (two males, five females; average age 34.9 years) was
      immunostained with a panel of antibodies for lymphohistiocytic markers: CD1a,
      CD3, CD4, CD8, CD15, CD20, CD56, TIA-1, CD68-PGM1, Mac387, and mast cell
      tryptase. Double immunolabeling was performed with CD1a/Mac387. Leder
      cytochemical stain for chloroacetate esterase was also performed. A moderate
      number of lymphocytes, predominantly T lymphocytes, were scattered diffusely
      within the lesions. The mean CD4/CD8 ratio was 0.1/1. The CD3/CD8 ratio (1.18/1)
      substantiated the CD4/CD8 ratio. The CD8 subset was CD56-negative and TIA-1
      positive, indicating a cytotoxic T lymphocyte phenotype. CD68-PGM1 was strongly
      positive in alveolar macrophages (AM) and weakly stained LC. Mac387, a marker of
      activated macrophages, weakly stained AM, while highlighting other interstitial
      cells. These interstitial cells appeared not to be LC (substantiated by
      CD1a/Mac387 dual labeling) or CD68-PGM-1-positive macrophages. Having excluded
      mast cells (positive with mast cell tryptase) and neutrophils (positive with CD15
      and Leder stains), there appeared to be a residual population of non-Langerhans
      cell monocytoid cells (NLMC), which were Mac 387+, CD68-PGM1-, Mast cell tryptase
      , CD15-, and CD1a-. Our results showed a predominance of CD8+, TIA-1+ cytotoxic T
      lymphocytes among the lymphocyte subsets which appear to interact with LC and AM
      in PLCH lesions. A small sub-population of NLMC was also present. Further studies
      are required to better define and to evaluate the role of cytotoxic T cells and
      NLMC in the pathogenesis of PLCH.

PMID- 18337021
TI  - Differential efficacy of combined therapy with radiation and AEE788 in high and
      low EGFR-expressing androgen-independent prostate tumor models.
AB  - PURPOSE: To determine the efficacy of combining radiation (XRT) with a dual
      epidermal growth factor receptor (EGFR)/vascular endothelial growth factor
      receptor inhibitor, AEE788, in prostate cancer models with different levels of
      EGFR expression. METHODS AND MATERIALS: Immunoblotting was performed for EGFR,
      phosphorylated-EGFR, and phosphorylated-AKT in prostate cancer cells. Clonogenic
      assays were performed on DU145, PC-3, and human umbilical vein endothelial cells
      treated with XRT +/- AEE788. Tumor xenografts were established for DU145 and PC-3
      on hind limbs of athymic nude mice assigned to four treatment groups: (1)
      control, (2) AEE788, (3) XRT, and (4) AEE788 + XRT. Tumor blood flow and growth
      measurements were performed using immunohistochemistry and imaging. RESULTS:
      AEE788 effectively decreased phosphorylated-EGFR and phosphorylated-AKT levels in
      DU145 and PC-3 cells. Clonogenic assays showed no radiosensitization for DU145
      and PC-3 colonies treated with AEE788 + XRT. However, AEE788 caused decreased
      proliferation in DU145 cells. AEE788 showed a radiosensitization effect in human
      umbilical vein endothelial cells and increased apoptosis susceptibility.
      Concurrent AEE788 + XRT compared with either alone led to significant tumor
      growth delay in DU145 tumors. Conversely, PC-3 tumors derived no added benefit
      from combined-modality therapy. In DU145 tumors, a significant decrease in tumor
      blood flow with combination therapy was shown by using power Doppler sonography
      and tumor blood vessel destruction on immunohistochemistry. Maldi-spectrometry
      (MS) imaging showed that AEE788 is bioavailable and heterogeneously distributed
      in DU145 tumors undergoing therapy. CONCLUSIONS: AEE788 + XRT showed efficacy in
      vitro/in vivo with DU145-based cell models, whereas PC-3-based models were
      adequately treated with XRT alone without added benefit from combination therapy.
      These findings correlated with differences in EGFR expression and showed effects
      on both tumor cell proliferation and vascular destruction.

PMID- 18337022
TI  - Influence of radiotherapy treatment concept on the outcome of patients with
      localized ependymomas.
AB  - PURPOSE: To assess the outcome of 57 patients with localized ependymomas treated
      with radiotherapy (RT). METHODS AND MATERIALS: Fifty-seven patients with
      localized ependymomas were treated with RT. Histology was myxopapillary
      ependymoma (n = 4), ependymoma (n = 23), and anaplastic ependymoma (n = 30). In
      16 patients, irradiation of the craniospinal axis (CSI) was performed with a
      median dose of 20 Gy. Forty-one patients were treated with local RT, with a local
      dose of 45 Gy to the posterior fossa, including a boost to the tumor bed of 9 Gy.
      In 19 patients, the tumor bed was irradiated with a median dose of 54 Gy.
      RESULTS: Overall survival after primary diagnosis was 83% and 71% at 3 and 5
      years. Five-year overall survival was 80% in low-grade and 79% in high-grade
      tumors. Survival from RT was 79% at 3 and 64% at 5 years. We could not show a
      significant difference in overall survival between CSI and local RT only. Freedom
      of local failure was 67% at 5 years in patients treated with CSI and 60% at 5
      years after local RT. A rate of 83% for distant failure-free survival could be
      observed in the CSI group as opposed to 93% in the group receiving local RT only.
      CONCLUSION: Local RT in patients with localized tumors is equieffective to CSI.
      The radiation oncologist must keep in mind that patients with localized
      ependymomas benefit from local doses > or =45 Gy.

PMID- 18337023
TI  - Dose-effect relationships for the submandibular salivary glands and implications
      for their sparing by intensity modulated radiotherapy.
AB  - PURPOSE: Submandibular salivary glands (SMGs) dysfunction contributes to
      xerostomia after radiotherapy (RT) of head-and-neck (HN) cancer. We assessed SMG
      dose-response relationships and their implications for sparing these glands by
      intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: A total of 148 HN
      cancer patients underwent unstimulated and stimulated SMG salivary flow rate
      measurements selectively from Wharton's duct orifices, before RT and periodically
      through 24 months after RT. Correlations of flow rates and mean SMG doses were
      modeled throughout all time points. IMRT replanning in 8 patients whose
      contralateral level I was not a target incorporated the results in a new cost
      function aiming to spare contralateral SMGs. RESULTS: Stimulated SMG flow rates
      decreased exponentially by (1.2%)(Gy) as mean doses increased up to 39 Gy
      threshold, and then plateaued near zero. At mean doses < or =39 Gy, but not
      higher, flow rates recovered over time at 2.2%/month. Similarly, the unstimulated
      salivary flow rates decreased exponentially by (3%)(Gy) as mean dose increased
      and recovered over time if mean dose was <39 Gy. IMRT replanning reduced mean
      contralateral SMG dose by average 12 Gy, achieving < or =39 Gy in 5 of 8
      patients, without target underdosing, increasing the mean doses to the parotid
      glands and swallowing structures by average 2-3 Gy. CONCLUSIONS: SMG salivary
      flow rates depended on mean dose with recovery over time up to a threshold of 39
      Gy. Substantial SMG dose reduction to below this threshold and without target
      underdosing is feasible in some patients, at the expense of modestly higher doses
      to some other organs.

PMID- 18337024
TI  - Effect of extra running on running-based taste aversion in rats.
AB  - Voluntary running in an activity wheel endowed rats with aversion to a taste
      solution consumed before the running. This running-based taste aversion was
      attenuated by extra running opportunities interspersed among the taste-running
      pairings, but the attenuating effect was reduced by signaling the extra running
      by another taste cue. These results correspond to the so-called degraded
      contingency effect and cover-cue effect in the traditional preparations of
      Pavlovian conditioning.

PMID- 18337025
TI  - Feasibility and outcome of substitution treatment of heroin-dependent patients in
      specialized substitution centers and primary care facilities in Germany: a
      naturalistic study in 2694 patients.
AB  - BACKGROUND: In many countries, buprenorphine and methadone are licensed for the
      maintenance treatment (MT) of opioid dependence. Despite many short-term studies,
      little is known about the long-term (12-month) effects of these treatments in
      different settings, i.e. primary care-based (PMC) and specialized substitution
      centers (SSCs). OBJECTIVES: To describe over a period of 12 months: (1)
      mortality, retention and abstinence rates; (2) changes in concomitant drug use,
      somatic and mental health; and (3) to explore differences between different types
      of provider settings. METHODS: 12-Month prospective-longitudinal naturalistic
      study with four waves of assessment in a prevalence sample of N=2694 maintenance
      patients, recruited from a nationally representative sample of N=223 substitution
      physicians. RESULTS: The 12-month retention rate was 75%; the mortality rate
      1.1%. 4.1% of patients became "abstinent" during follow-up. 7% were referred to
      drug-free addiction treatment. Concomitant drug use decreased and somatic health
      status improved. No significant improvements were observed for mental health and
      quality of life. When controlling for initial severity, small PMC settings
      revealed better retention, abstinence and concomitant drug use rates. CONCLUSION:
      The study underlines the overall 12-month effectiveness of various forms of
      agonist MT. Findings reveal relatively high retention rates, low mortality rates,
      and improvements in most 12-month outcome domains, except for mental health and
      quality of life. PMC settings appear to be a good additional option to improve
      access to MTs.

PMID- 18337026
TI  - Complete nucleotide sequence and organization of the mitogenome of the silk moth
      Caligula boisduvalii (Lepidoptera: Saturniidae) and comparison with other
      lepidopteran insects.
AB  - The 15,360-bp long complete mitogenome of Caligula boisduvalii possesses a gene
      arrangement and content identical to other completely sequenced lepidopteran
      mitogenomes, but different from the common arrangement found in most insect
      order, as the result of the movement of tRNA(Met) to a position 5'-upstream of
      tRNA Ile. The 330-bp A+T-rich region is apparently capable of forming a stem-and
      loop structure, which harbors the conserved flanking sequences at both ends.
      Dissimilar to what has been seen in other sequenced lepidopteran insects, the
      initiation codon for C. boisduvalii COI appears to be TTG, which is a rare, but
      apparently possible initiation codon. The ATP8, ATP6, ND4L, and ND6 genes, which
      neighbor another PCG at their 3' end, all harbored potential sequences for the
      formation of a hairpin structure. This is suggestive of the importance of such
      structures for the precise cleavage of the mRNA of mature PCGs. Phylogenetic
      analyses of available sequenced species of Bombycoidea, Pyraloidea, and
      Tortricidea supported the morphology-based current hypothesis that Bombycoidea
      and Pyraloidea are monophyletic (Obtectomera). As previously suggested,
      Bombycidae (Bombyx mori and B. mandarina) and Saturniidae (Antheraea pernyi and
      C. boisduvalii) formed a reciprocal monophyletic group.

PMID- 18337027
TI  - Preclinical characterisation of NSAIDs in ultradeformable carriers or
      conventional topical gels.
AB  - We compared in vivo transport and biodistribution of ketoprofen applied on the
      skin in ultradeformable carriers (Diractin) or a conventional topical gel
      (Gabrilen) with oral drug (Oruvail); for reference we used in vitro study data.
      The drug from Gabrilen diffuses into body with low bioavailability (<10%) and
      limited regio-selectivity (AUC(deep muscle/plasma) approximately 45/0.8 (t=0-8h),
      reaching maximum concentration in subcutaneous tissues and plasma at similar time
      (t(max) approximately 3-4h). The apparent drug elimination half-life is then
      similar to oral ketoprofen (t1/2,a) approximately 2 h). In contrast, Diractin
      containing ultradeformable carriers (Transfersome vesicles) delivers the drug
      more efficiently (>50%) and more directly into peripheral muscles (AUC(deep
      muscle/plasma) approximately 447/0.7 (652/1.4) for t=0-8 (0-24)h; tmax
      approximately 1 h), arguably in non-diffusive fashion. Ketoprofen from Diractin
      moreover disappears from body periphery slower (t1/2,a) approximately 4-6 h),
      owing to sustained drug release from the carriers in target tissue. Final
      clearance always proceeds via plasma (tmax approximately 4 h). Epicutaneous
      application of ketoprofen in conventional gels or the carrier-based formulation
      thus leads to different local accumulations and clearances. Ketoprofen from
      Diractin achieves more desirable biodistribution and clearance, arguably due to
      spontaneous carrier-mediated drug transport across the skin, which ensures local
      and relatively long-lasting drug deposition into peripheral target tissues.

PMID- 18337028
TI  - Crosslinking of drug-alginate granules. Part 2. Effect of granule preparation and
      composition on granule properties.
AB  - Paracetamol-alginate (Keltone HVCR) (1:1) granules were prepared by a wet
      granulation process followed by crosslinking of dried granules in calcium
      chloride solution. The effect of shear (planetary (low), Brabender (high)),
      binder quantity (1:2, 1:1 water:powder) and drug particle size (PS 98, 275
      microm) were studied using a factorial design. Supporting studies were carried
      out varying binder quantity and alginate grade (viscosity). In the pre-treated
      granules, drug entrapment was mainly influenced by drug PS, where the smaller
      particles showed better embedding. After crosslinking, drug particle size
      continued to be the most important factor influencing drug recovery. All factors
      influenced early stage release where high shear, high binder, small drug PS
      granules showed least release and the low shear, low binder and large drug PS
      granules showed greatest release. Some significant two-factor interactions were
      found. Granule consolidation (shown by SEM) and particle embedding increased with
      binder quantity and reduced as the alginate viscosity was increased.
      Crosslinking, as shown by Na and Ca contents was >90%. The impact of granule
      consolidation on drug entrapment and recovery was relatively small (<10%) when
      compared to its effect on early stage drug release (>60%) which may be important
      if these granule systems are to be used for taste improvement.

PMID- 18337029
TI  - Development of an implantable infusion pump for sustained anti-HIV drug
      administration.
AB  - Factors such as insufficient drug potency, non-compliance and restricted tissue
      penetration contribute to incomplete suppression of Human Immunodeficiency Virus
      (HIV) and the difficulty to control this infection. Infusion via standard
      catheters can be a source of infection, which is potentially life threatening in
      these patients. We developed an implantable infusion pump, allowing to
      accommodate large volumes (16-50mL) of high viscous solutions (up to 23.96mPas at
      39 degrees C) of anti-HIV agents and providing sustained release of medication: a
      standard Codman 3000 pump, which was initially developed to release aqueous
      solutions ( approximately 0.7mPas) into the spinal cord such as for pain
      medication, was transformed for release of viscous solutions up to 40mPas by
      adapting the diameter of the capillary flow restrictor, the capillary length and
      way of catheterisation--by placing the indwelling catheter in the vena cava. A
      pilot study of the pump implanted in 2 dogs showed continuous steady-state
      release of the protease inhibitor darunavir (25mg/dog/day administered for 25
      days), thereby achieving plasma concentration levels of approximately 40ng/mL.
      Steady-state plasma levels were reproducible after monthly refill of the pumps.
      In conclusion, the implantable adapted Codman 3000 constant-flow infusion pump
      customized to anti-HIV therapy allows sustained release of anti-HIV medication
      and may represent an opportunity to reduce the pill burden and complexity of
      dosing schemes associated with common anti-HIV therapy.

PMID- 18337030
TI  - Transdermal permeation enhancement of N-trimethyl chitosan for testosterone.
AB  - The aim of this study was to evaluate the transdermal permeation enhancement of N
      trimethyl chitosan (TMC) with different degrees of quaternization (DQ). TMCs with
      DQ of 40 and 60% (TMC40 and TMC60) were synthesized and characterized by (1)H
      NMR. Testosterone (TS) used as an effective drug, four different gels were
      prepared without enhancer, with 5% TMC40, 5% TMC60 or 2% Azone, respectively as
      enhancer. The effect of TMC60 on the stratum corneum was studied by Attenuated
      Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) combined with
      the technique of deconvolution. The results showed that TMC60 could significantly
      affect the secondary structure of keratin in stratum corneum. In vitro permeation
      studies were carried out using Franz-diffusion cells and in vivo studies were
      performed in rabbits. Both in vitro and in vivo permeation studies suggested the
      transdermal permeation enhancement of TMCs. Compared to the TS gel without
      enhancer, TS gels with enhancers all showed significant enhancing effect on
      transdermal permeation of TS (P<0.05). Meanwhile, compared to 2% Azone, 5% TMC60
      had a stronger enhancement (P<0.05) while 5% TMC40 had a similar effect (P>0.05).
      The results suggested that the enhancement of TMCs increased with the increase of
      DQ.

PMID- 18337031
TI  - Cytotoxic sesquiterpenoids from the ethanol extract of fruits of Celastrus
      orbiculatus.
AB  - AIM OF THE STUDY: To investigate the cytotoxic compounds against human melanoma
      A375-S2 and human cervical carcinoma Hela cell lines from the fruits of Celastrus
      orbiculatus. MATERIALS AND METHODS: The ethanol extract of the fruits of C.
      orbiculatus was found to exhibit significant cytotoxic activity. After partition,
      the column chromatography and Semi-preparative HPLC were used for activity guided
      fractionation from the active petroleum ether-soluble part. NMR and ESI-MS
      spectra for structure analysis were recorded on spectrometers, respectively. The
      cytotoxic activities of the isolated compounds were determined using the MTT
      assay. RESULTS: Four sesquiterpenoids (1-4) were isolated by activity guided
      fractionation from the ethanol extract of the fruits of C. orbiculatus. Compounds
      1-3 exhibited promising cytotoxicities against the Hela cells and A375-S2 cells.
      The cytotoxic activities of compounds 1-3 seemed to be dose-dependent, which
      exhibited more potent inhibition for the proliferation of two cell lines when
      increased the concentrations of every compounds. Among these compounds, compound
      2 showed most cytotoxicities against either Hela cells or the A375-S2 cells.
      CONCLUSIONS: The cytotoxic activity of the ethanol extract of fruits of C.
      orbiculatus against human melanoma A375-S2 and human cervical carcinoma Hela
      cells due to its content of sesquiterpenoids, supports its potential therapeutic
      value for the treatment of tumor.

PMID- 18337032
TI  - Anticonvulsant effect of Rhus chirindensis (Baker F.) (Anacardiaceae) stem-bark
      aqueous extract in mice.
AB  - Extracts of Rhus chirindensis stem-bark are used extensively in South African
      traditional medicines for the treatment, management and/or control of an array of
      human ailments, including childhood convulsions and epilepsy. In this study, we
      investigated the anticonvulsant activity of the plant's stem-bark aqueous extract
      (RCE, 50-800 mg/kg i.p.) against pentylenetetrazole (PTZ)-, picrotoxin (PCT)- and
      bicuculline (BCL)-induced seizures in mice. Phenobarbitone and diazepam were used
      as reference anticonvulsant drugs for comparison. Single intraperitoneal
      injections of PTZ (90 mg/kg), PCT(10 mg/kg) or BCL (30 mg/kg) produced tonic
      clonic seizures. Like the standard antiseizure drugs used, Rhus chirindensis stem
      bark aqueous extract (RCE, 100-800 mg/kg i.p.) significantly delayed (p<0.05
      0.001) the onset of, and antagonized pentylenetetrazole-induced seizures. The
      plant's stem-bark aqueous extract (RCE, 100-800 mg/kg i.p.) also profoundly
      antagonized picrotoxin-induced seizures, but only weakly antagonized bicuculline
      induced seizures. Although the data obtained in the present study do not provide
      conclusive evidence, it would appear that RCE produces its antiseizure effect by
      enhancing GABAergic neurotransmission and/or action in the brain. The results of
      this laboratory animal study indicate that RCE possesses anticonvulsant activity
      in the mammalian experimental model used, and thus suggest that the plant may be
      used as a natural supplementary remedy in the management, control and/or
      treatment of childhood convulsions and epilepsy. In conclusion, the findings of
      this study lend pharmacological credence to the suggested folkloric, ethnomedical
      uses of Rhus chirindensis in the management of childhood convulsions and epilepsy
      in some rural communities of South Africa.

PMID- 18337033
TI  - Rama midwifery in eastern Nicaragua.
AB  - Rama midwives in eastern Nicaragua use a wide array of plants in providing health
      care to women and infants. In this study, I document the use of medicinal plants
      by Rama midwives on the island of Rama Cay in eastern Nicaragua. Field
      investigations included semi-structured interviews and field trips with eight
      midwives to collect voucher specimens. A total of 162 plant species, in 125
      genera and 62 families were documented as useful in midwifery, over 5 years of
      fieldwork. Most (59%) medicinals are obtained from second-growth forest, and are
      used to treat more than 35 human ailments. Over 90% have some bioactive
      principle, most are trees (40%) or herbs (31%), and leaves are the most
      frequently used plant part. Most herbal remedies are prepared as decoctions and
      are administered orally. Most midwifery species are wild, but many important
      species are introduced domesticates native to the NW and OW tropics. This study
      is important because it is the first systematic study of midwifery in eastern
      Nicaragua and particularly of Rama midwifery. Eastern Nicaragua is a region
      undergoing tremendous changes, and the Rama are a people highly acculturated, but
      with very little documentation of their ethnobotanical heritage. Based on the
      results of this study I believe that for the near future, the Rama will continue
      to rely on midwifery as a primary source of health care.

PMID- 18337034
TI  - Study of embryotoxicity of Perovskia abrotanoides, an adulterant in folk
      medicine, during organogenesis in mice.
AB  - AIM OF THE STUDY: Perovskia abrotanoides is a medicinal herb which traditionally
      has been used as a topical application to treat leishmaniasis in Iran. Due to
      similarities of the flowers of Perovskia abrotanoides and Echium species, it is
      added as an adulterant to Echium preparations in Iran. Echium flowers have been
      used in Iranian traditional medicine as an "anti-stress", tranquilizer, and
      energizer drink, fighting common cold and bronchitis particularly during
      pregnancy. In this study, the in vivo embryotoxicity of 0.125 and 0.25 g/kg of
      ethanolic and aqueous extracts of Perovskia abrotanoides during organogenesis in
      mice has been investigated. MATERIALS AND METHODS: Maternal body weights were
      recorded and pregnant females were observed daily throughout gestation. After
      cesarean section, fetuses were weighed, lengthed and examined for gross external
      malformations. Others were fixed then stained with Alcian blue and Alizarin red
      to view any skeletal malformations. RESULTS: Our results indicated that this herb
      causes minimal maternal toxicity, while resorption, stillborn, fetal
      malformations including polydactyly, spina bifida, aglossia, tarsal extensor,
      gastroschisis, and numerous skeletal abnormalities were detected particularly in
      the ethanolic extract groups. Specific skeletal abnormalities based on type of
      extract were also observed. CONCLUSIONS: Since Perovskia abrotanoides is widely
      used in traditional medicine intentionally or inadvertently, it is advisable its
      use during pregnancy should be avoided and strict regulations are imposed to
      prevent its addition to commercial preparations of other herbal products.

PMID- 18337035
TI  - Purification of a dimethyladenosine compound from silkworm pupae as a
      vasorelaxation substance.
AB  - To identify the active substance in the male silkworm pupae that strengthens
      men's vitality, the vasorelaxation activity was determined by measuring the
      vascular endothelial nitric oxide (eNO) produced in calf pulmonary artery
      endothelial (CPAE) cells treated with extracts from the pupae. Dried silkworm
      male pupae were extracted with ethanol and suspended in water, then partitioned
      with hexane, chloroform, ethylacetate, and butanol, sequentially. Among these
      fractions, the aqueous fraction had maximal NO production (156.87 microM/200
      microl well, 10 mg/ml) and minimal cytotoxicity (IC50 362.3 mg/ml). The
      vasorelaxation substances (VAS) from the aqueous fraction were isolated by a
      combination of gel filtration and anion-exchange chromatography on DEAE Sephadex
      A-25 and reverse phase-HPLC. Their chemical structures were determined on the
      basis of their spectroscopic parameters of EI-MS, MALDI-TOF MS, 1H and 13C NMR,
      1H-1H COSY, and GC-MS spectral data. The active substance was subsequently
      identified as a dimethyladenosine and dimethyladenosine-5'-L-arabinose that has
      phosphodiesterase (PDE) inhibition activity. This compound was shown to inhibit
      PDE4 activity in a dose-dependent manner. Also, it inhibited the PDE5 activity of
      cyclic-GMP-specific PDE5 enzyme. These results imply that dimethyladenosine may
      be a lead compound for the development and improvement of vasculogenic impotence
      drugs through phosphodiesterase inhibition and NO production in endothelial
      cells.

PMID- 18337036
TI  - [Radiologic diagnosis of enterosalpingeal fistula complicating Crohn's disease].
AB  - Enterosalpingeal fistula is a rare complication of Crohn's disease which is
      rarely diagnosed preoperatively. We describe a new case of this complication
      suspected by CT scan and confirmed by hysterosalpingogram and contrast from the
      ileum. This case is about a 50-year-old woman suffering from ileal Crohn's
      disease diagnosed two years previously and actually complicated by stenosis and
      entero-salpingeal fistula. The treatment consisted on resection of the ileocaecal
      region with salpingectomy. Postoperative course was uneventful.

PMID- 18337037
TI  - DCFH2 interactions with hydroxyl radicals and other oxidants--influence of
      organic solvents.
AB  - The oxidation of 2',7'-dichlorofluorescin (DCFH(2)) is widely used as a measure
      to detect the generation of reactive oxygen species (ROS) and to analyze
      oxidative stress. Other factors beside commonly known radicals may influence the
      results of such measurements. Therefore, the effects of H(2)O(2), KMnO(4,)
      decomposition products of AAPH, ethanol and DMSO, antioxidants like ascorbic
      acid, different ferrous ion chelates, and heme-containing proteins like
      cytochrome c, myoglobin, hemoglobin, and horseradish-peroxidase were
      comparatively analyzed with respect to their impact on DCFH(2) oxidation. The
      study evaluates the effects of various oxidants with different oxidative
      potentials regarding their ability to induce DCF-fluorescence. Furthermore, we
      analyzed the inhibitory effect of organic solvents like ethanol or DMSO on the
      oxidation of DCFH(2) by hydroxyl radicals. The results of our study indicate that
      the potential of an oxidant does not always correlate with its efficiency to
      generate DCF-fluorescence.

PMID- 18337038
TI  - Effects of aluminium sulphate in the mouse liver: similarities to the aging
      process.
AB  - Aluminium (Al) is a ubiquitous metal that is potentially toxic to the brain. Its
      effects on other fundamental organs are not completely understood. This
      morphological in vivo study sought to compare sublethal hepatotoxic changes and
      Al deposition in adult mice that orally ingested Al sulphate daily for 10 months,
      in age matched control mice that drank tap water and in senescent mice (24 months
      old). Livers were examined for collagen deposition using Sirius red and Masson,
      for iron accumulation using Perls' stain. Light, electron microscopy and
      morphometry were used to assess fibrosis and vascular changes. Scanning
      transmission electron microscopy and EDX microanalysis were used to detect in
      situ elemental Al. Iron deposition, transferrin receptor expression were
      significantly altered following Al exposure and in the aged liver but were
      unaffected in age matched control mice. In Al treated mice as in senescent mice,
      endothelial thickness was increased and porosity was decreased like
      perisinusoidal actin. Furthermore, Al stimulated the deposition of collagen and
      laminin, mainly in acinar zones 1 and 3. Pseudocapillarization and periportal
      laminin in senescent mice were similar to Al treated adult liver. In conclusion,
      prolonged Al sulphate intake accelerates features of senescence in the adult mice
      liver.

PMID- 18337039
TI  - Cervical lymph nodes.
AB  - The lymph node staging is a very important prognostic parameter for patients with
      presenting with head neck cancer and is influencing the selection of the
      different therapeutic strategies including surgery, chemotherapy, radiotherapy or
      a combination of them. The accuracy of imaging techniques, such as US, MR
      imaging, and CT, depends on the appropriateness of radiological criteria used for
      diagnosing lymph node metastases. Size of nodes and evidence of necrosis are
      still the most important radiological criteria. However, the size shows great
      variability. A spherical lymph node larger than 10mm is an indicator for a
      malignant node, whereas an oval shape and/or a fatty hilus are more benign signs.
      But there are many limitations and different cut offs published in the
      literature, indicating that the size of a lymph node is not a reliable criteria
      for the assessment of lymph nodes in the head and neck region. Today new high
      resolution MRI sequences and the development of specific contrast agents are
      offering new possibilities in the diagnostic work-up of head and neck lymph
      nodes. Ultrasmall superparamagnetic iron oxide particles (USPIO's) are resulting
      after intravenous application in a reduction of the T2 relaxation time. This is
      causing a signal decrease on T2-weighted MR images in benign lymph nodes after
      administration of USPIO's, whereas malignant lymph nodes do not show a
      significant signal decrease. Some clinical studies presented already very
      promising results. Based on the fact, that the size evaluation of lymph nodes in
      the head and neck has not changed during the last decade, this paper will mainly
      focus on MRI with new contrast agents and new techniques as diffusion weighted
      imaging (DWI).

PMID- 18337040
TI  - Pulmonary alterations in Behcet's disease.
AB  - PURPOSE: This study aims to demonstrate pulmonary alterations (PA) in patients
      with Behcet's disease by using CT. MATERIALS AND METHODS: CTs of 50 patients with
      Behcet's disease and 20 others in a control group have been evaluated
      retrospectively for PA (septal, reticular, nodular, atelectatic opacities).
      RESULTS: Eight out of 50 patients (16%) with Behcet's disease showed PA. Three
      out of 20 (15%) in the control group showed PA. No differences were observed
      between Behcet's disease patients and the control group regarding pulmonary
      alterations (p=0.917). No differences were observed in the disease duration, ages
      and sex in either group in those with and without PA. CONCLUSION: Pulmonary
      alterations can be seen in patients with Behcet's disease, but these alterations
      are not significant.

PMID- 18337041
TI  - Imaging of salivary gland tumours.
AB  - Salivary gland neoplasms account for <3% of all tumors. Most of them are benign
      and parotid gland is the commonest site. As a general rule, the smaller the
      involved salivary gland, the higher is the possibility of the tumor being
      malignant. The role of imaging in assessment of salivary gland tumour is to
      define intra-glandular vs. extra-glandular location, detect malignant features,
      assess local extension and invasion, detect nodal metastases and systemic
      involvement. Image guided fine needle aspiration cytology provides a safe means
      to obtain cytological confirmation. For lesions in the superficial parotid and
      submandibular gland, ultrasound is an ideal tool for initial assessment. These
      are superficial structures accessible by high resolution ultrasound and FNAC
      which provides excellent resolution and tissue characterization without a
      radiation hazard. Nodal involvement can also be assessed. If deep tissue
      extension is suspected or malignancy confirmed on cytology, an MRI or CT is
      mandatory to evaluate tumour extent, local invasion and perineural spread. For
      all tumours in the sublingual gland, MRI should be performed as the risk of
      malignancy is high. For lesions of the deep lobe of parotid gland and the minor
      salivary glands, MRI and CT are the modalities of choice. Ultrasound has limited
      visualization of the deep lobe of parotid gland which is obscured by the
      mandible. Minor salivary gland lesions in the mucosa of oral cavity, pharynx and
      tracheo-bronchial tree, are also not accessible by conventional ultrasound.
      Recent study suggests that MR spectroscopy may differentiate malignant and benign
      salivary gland tumours as well as distinguishing Warthin's tumor from pleomorphic
      adenoma. However, its role in clinical practice is not well established.
      Similarly, the role of nuclear medicine and PET scan, in imaging of parotid
      masses is limited. Sialography is used to delineate the salivary ductal system
      and has limited role in assessment of tumour extent.

PMID- 18337042
TI  - Cost reduction in abdominal CT by weight-adjusted dose.
AB  - AIM: To analyze the influence of contrast dose adjusted by weight vs. fixed
      contrast dose in the attenuation and cost of abdominal computed tomography (CT).
      MATERIALS AND METHODS: A randomised, consecutive, parallel group study was
      conducted in 151 patients (74 men and 77 women, age range 22-67 years), studied
      with the same CT helical protocol. A dose at 1.75 ml/kg was administered in 101
      patients while 50 patients had a fixed dose of 120 ml of same non-ionic contrast
      material (320 mg/ml). Mean enhancements were measured at right hepatic lobe,
      superior abdominal aorta and inferior cava vein. Statistical analysis was weight
      stratified (<60, 61-70, 71-80 and >81 kg). RESULTS: Aortic attenuation was
      significantly superior (p<0.05) in the dose adjusted by weight group than in the
      fixed dose group. Patients who weighed >61 kg in dose-adjusted group, presented
      higher hepatic attenuation, being statistically significant in those >81 kg
      (p<0.01). In dose-adjusted group, there was a savings of euro 4.1 per patient in
      patients weighing <80 kg. In patients weighing >80 kg, there was an over cost of
      euro 10.7 per patient. CONCLUSIONS: An injection volume of 1.75 ml/kg offers an
      optimal diagnostic quality with a global savings of euro 1.34 per patient.

PMID- 18337043
TI  - CT and endoscopic ultrasound in comparison to endoluminal MRI: preliminary
      results in staging gastric carcinoma.
AB  - PURPOSE: To prospectively compare diagnostic parameters of a newly developed
      endoluminal MRI (endo-MRI) concept with endoscopic ultrasound (EUS) and hydro
      computer tomography (Hydro-CT) in T-staging of gastric carcinoma on one patient
      collective. MATERIAL AND METHODS: 28 consecutive patients (11 females, 17 males,
      age range 46-87 years, median 67 years) referred for surgery due to a gastric
      malignancy were included. Preoperative staging by EUS was performed in 14 cases
      and by Hydro-CT in 14 cases within a time frame of 2 weeks. Ex vivo endo-MRI
      examination of gastric specimens was performed directly after gastrectomy within
      a time interval of 2-3h. EUS data were acquired from the clinical setting whereas
      Hydro-CT and endo-MRI data were evaluated in blinded fashion by two experienced
      radiologists and one surgeon well experienced in EUS on gastric carcinomas.
      RESULTS: Histopathology resulted in 4 pT1, 17 pT2, 3 pT3 and 2 pT4 carcinomas
      with 2 gastric lymphomas which were excluded. Overall accuracy for endo-MRI was
      75% for T-Staging of the 26 carcinomas. EUS achieved 42.9% accuracy; endo-MRI in
      this subgroup was accurate in 71.4%. Hydro-CT was correct in 28.6%, accuracy for
      endo-MRI in this subgroup was 71.4%. CONCLUSION: The direct comparison of all
      three modalities on one patient collective shows that endo-MRI is able to achieve
      adequate staging results in comparison with clinically accepted methods like EUS
      and Hydro-CT in classifying the extent of tumor invasion into the gastric wall.
      However the comparison is limited as we compared in vivo routine clinical data
      with experimental ex vivo data. Future investigations need to show if the
      potential of endo-MRI can be transferred into a clinical in vivo setting.

PMID- 18337044
TI  - Histopathological perspective on bone marrow oedema, reactive bone change and
      haemorrhage.
AB  - This article presents a systematic review of the current biomedical literature
      surrounding the aetiopathogenesis and histopathological features of bone marrow
      oedema, reactive bone change and haemorrhage. Bone marrow oedema is generally
      demonstrated as a non-specific finding on magnetic resonance imaging in
      association with infections, tumours and avascular necrosis. When it occurs in
      isolation as a primary event not triggered by any obvious bony pathology in the
      clinical setting of debilitating joint pain, it constitutes the "bone marrow
      oedema syndrome". Although the latter diagnosis is based on magnetic resonance
      (MR) imaging, showing the lesion as areas of signal hyperintensity within the
      marrow, recent radiology-histology correlational studies have shown variably
      interstitial marrow oedema, necrosis, fibrosis and trabecular bone abnormalities.
      In light of these facts, the use of the term bone marrow oedema syndrome in a
      radiological context might be considered questionable, but histopathological
      techniques are not sensitive in detecting increased extracellular fluid. Reactive
      bone changes may be focal or diffuse and usually amount to increased bone
      formation. Bone marrow haemorrhage, due to trauma, results in bone bruising, a
      condition in which the size of the bruise and associated osteochondral injury
      determines the outcome, although the natural history of these lesions is still
      being researched.

PMID- 18337045
TI  - The performance of computer-aided detection when analyzing prior mammograms of
      newly detected breast cancers with special focus on the time interval from
      initial imaging to detection.
AB  - PURPOSE: The clinical role of CAD systems to detect breast cancer, which have not
      been on cancer containing mammograms not detected by the radiologist was proven
      retrospectively. METHODS: All patients from 1992 to 2005 with a histologically
      verified malignant breast lesion and a mammogram at our department, were analyzed
      in retrospect focussing on the time of detection of the malignant lesion. All
      prior mammograms were analyzed by CAD (CADx, USA). The resulting CAD printout was
      matched with the cancer containing images yielding to the radiological diagnosis
      of breast cancer. CAD performance, sensitivity as well as the association of CAD
      and radiological features were analyzed. RESULTS: 278 mammograms fulfilled the
      inclusion criteria. 111 cases showed a retrospectively visible lesion (71 masses,
      23 single microcalcification clusters, 16 masses with microcalcifications, in one
      case two microcalcification clusters). 54/87 masses and 34/41 microcalcifications
      were detected by CAD. Detection rates varied from 9/20 (ACR 1) to 5/7 (ACR 4)
      (45% vs. 71%). The detection of microcalcifications was not influenced by breast
      tissue density. CONCLUSION: CAD might be useful in an earlier detection of subtle
      breast cancer cases, which might remain otherwise undetected.

PMID- 18337046
TI  - Development of a chromatographic fingerprint for the chloroform extracts of
      Ganoderma lucidum by HPLC and LC-MS.
AB  - A new high-performance liquid chromatographic (HPLC) fingerprinting method was
      developed for the quality control of Ganoderma lucidum. Twenty-nine batches
      obtained from three different origins in China were used to establish the
      fingerprint. The constituents of these samples were separated with a Kromasil
      C(18) column (250 mm x 4.6 mm, 5 microm) by linear gradient elution using water
      acetic acid (100:0.1, v/v) and acetonitrile as mobile phase components at a flow
      rate of 0.8 ml/min and detector wavelength at 254 nm. Mean chromatograms and
      correlation coefficients of samples were calculated by the software "Similarity
      Evaluation System for Chromatographic Fingerprint of TCM". There were 19 common
      peaks in this fingerprint. Eleven of these common peaks were tentatively
      identified with reference to literature data based on their liquid chromatography
      electrospray ionization-tandem mass spectrometry (LC-ESI-MS) and UV data. This
      profile was then successfully used to identify and assess the differences among
      samples from various origins with the aid of similarity analysis. The diverse
      similarities among different samples indicated that the quality of G. lucidum was
      not stable and the products from different areas were inconsistent. All results
      showed that the developed fingerprint assay was specific and could further serve
      for quality identification and comprehensive evaluation of G. lucidum.

PMID- 18337047
TI  - Biological degradation of plastics: a comprehensive review.
AB  - Lack of degradability and the closing of landfill sites as well as growing water
      and land pollution problems have led to concern about plastics. With the
      excessive use of plastics and increasing pressure being placed on capacities
      available for plastic waste disposal, the need for biodegradable plastics and
      biodegradation of plastic wastes has assumed increasing importance in the last
      few years. Awareness of the waste problem and its impact on the environment has
      awakened new interest in the area of degradable polymers. The interest in
      environmental issues is growing and there are increasing demands to develop
      material which do not burden the environment significantly. Biodegradation is
      necessary for water-soluble or water-immiscible polymers because they eventually
      enter streams which can neither be recycled nor incinerated. It is important to
      consider the microbial degradation of natural and synthetic polymers in order to
      understand what is necessary for biodegradation and the mechanisms involved. This
      requires understanding of the interactions between materials and microorganisms
      and the biochemical changes involved. Widespread studies on the biodegradation of
      plastics have been carried out in order to overcome the environmental problems
      associated with synthetic plastic waste. This paper reviews the current research
      on the biodegradation of biodegradable and also the conventional synthetic
      plastics and also use of various techniques for the analysis of degradation in
      vitro.

PMID- 18337048
TI  - Catalpol protects primary cultured astrocytes from in vitro ischemia-induced
      damage.
AB  - Catalpol, an iridoid glycoside abundant in the roots of Rehmannia glutinosa, has
      been previously found to prevent the loss of CA1 hippocampal neurons and to
      reduce working errors in gerbils after ischemia-reperfusion injury. In the
      present study, we investigated the effects of catalpol on astrocytes in an
      ischemic model to further characterize its neuroprotective mechanisms. Primary
      cultured astrocytes exposed to oxygen-glucose deprivation (OGD) followed by
      reperfusion (adding back oxygen and glucose, OGD-R), were used as an in vitro
      ischemic model. Treatment of the astrocytes with catalpol during ischemia
      reperfusion increased astrocyte survival significantly in a concentration
      dependent manner, as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release and
      morphological observation. In addition, catalpol prevented the decrease in
      mitochondrial membrane potential, inhibited the formation of reactive oxygen
      species (ROS) and the production of nitric oxide (NO), decreased the level of
      lipid peroxide and the activity of inducible nitric oxide synthase (iNOS), and
      elevated the activities of superoxide dismutase (SOD), glutathione peroxidase
      (GPx) and the content of glutathione (GSH). Our results suggest that catalpol
      exerts the most significant cytoprotective effect on astrocytes by suppressing
      the production of free radicals and elevating antioxidant capacity.

PMID- 18337049
TI  - Nurse and patient communication profiles in a home-based telehealth intervention
      for heart failure management.
AB  - OBJECTIVE: This study compared differences in nurse and patient communication
      profiles between two telehealth modes: telephone and videophone, and evaluated
      longitudinal changes in communication, nurse perceptions, and patient
      satisfaction. METHODS: Subjects were enrolled in a randomized controlled clinical
      trial evaluating a 90-day home-based intervention for heart failure. Telephone
      (n=14) and videophone (n=14) interactions were audio taped and analyzed using the
      Roter Interaction Analysis System. RESULTS: Nurses were more likely to use open
      ended questions, back-channel responses, friendly jokes, and checks for
      understanding on the telephone compared to videophone. Compliments given and
      partnership were more common on the videophone. Patients were more likely to give
      lifestyle information and approval comments on the telephone, and used more
      closed-ended questions on the videophone. Nurses perceptions of the interactions
      were not different between the telephone and videophone, nor did their
      perceptions change significantly over the course of the intervention. There were
      no significant differences in patient satisfaction between the telephone and
      videophone. CONCLUSIONS: The results of this study did not support use of a
      videophone over the telephone. PRACTICE IMPLICATIONS: It is critical to match
      technologies to patient needs and use the least complex technology possible. When
      considering use a videophone, health care providers should critically examine the
      trade-offs between additional complexities with the added value of the visual
      interaction.

PMID- 18337050
TI  - Development and feasibility of a patient feedback programme to improve
      consultation skills in general practice training.
AB  - OBJECTIVE: To develop an attractive and effective patient feedback training
      programme for general practice trainees (GPTs). METHODS: First, an exploratory
      study was conducted in which patients and GPTs were interviewed after they had
      worked with patient feedback. This contributed to the development of the patient
      feedback training programme. Subsequently, in a feasibility study, first-year
      GPTs asked patients to give feedback on their consultation skills by completing a
      questionnaire. The outcomes of group discussions with the GPTs and the results of
      the evaluation forms filled in by the GPTs were analysed. RESULTS: Forty-eight
      GPTs collected 878 questionnaires. GPTs and patients alike expected patient
      feedback to be a major tool for acquiring consultation skills. The GPTs
      encountered several obstacles in the organisation of this programme in their
      practice. They reported that the learning effects were more limited than they had
      expected because patients gave positively biased answers and because not all
      consultations provided an appropriate source of patient feedback. CONCLUSION: The
      new patient feedback programme on consultation skills is feasible for patients
      and GPTs. PRACTICE IMPLICATIONS: To optimise the educational potential and
      benefits of patient feedback, GPTs should ask for feedback from patients after
      challenging consultations, and should stimulate patients to be critical in their
      answers.

PMID- 18337051
TI  - Discussing preferences for cardiopulmonary resuscitation: what do resident
      physicians and their hospitalized patients think was decided?
AB  - OBJECTIVE: To explore the ways in which seriously ill hospitalized patients,
      their family members and physicians interpret the discussion of the patient's
      preferences for cardiopulmonary resuscitation (CPR). METHODS: Resident
      physicians, their patients, and family members were interviewed following a
      discussion regarding preferences for CPR. We sought the participants' perceptions
      of the resulting decision, examined how often these interpretations differed, and
      explored the communicative factors underlying discrepancies when they occurred.
      RESULTS: Fifty-six interviews with 28 matched dyads were completed. In six dyads
      (21%), the participants reported differing results of the discussion. Two
      patients had orders to limit their care based on the physician's interpretation
      of their discussion. Another two patients who did not want resuscitation lacked a
      DNR order. Two patients did not recall having the conversation. These
      discrepancies could be attributed to the physician misconstruing the patient's
      wishes, interference of a family member, and fluctuating preferences.
      CONCLUSIONS: Discrepant interpretations of a DNR discussion occur with a
      concerning frequency between resident physicians and their hospitalized patients.
      PRACTICE IMPLICATIONS: Educational efforts should focus on training physicians to
      clarify the language used in these discussions, remain vigilant about discerning
      the patient's preferences, and be aware that these preferences may be
      contextually fluid.

PMID- 18337052
TI  - Depressed patients' preferences for education about medications by pharmacists in
      Kuwait.
AB  - OBJECTIVE: To assess patients' opinion toward receiving written or specialized
      verbal pharmacists' interventions and to determine the effect of these
      interventions on patients' medication knowledge. METHODS: 150 newly diagnosed
      patients with unipolar depression and initiated with a single antidepressant were
      randomized into 3 groups: control, leaflet and counselling, and interviewed at
      initiation and after 6-8 weeks of treatment at the outpatient department of the
      Psychiatric Hospital in Kuwait. RESULTS: 50% of respondents asserted that
      clinicians did not give them sufficient information while 90% favoured the idea
      of receiving further information about therapy. Forty seven percent of
      participants failed to return for the second follow-up appointment. The drop-out
      rate was 66% in the control, 42% in the Leaflet and only 34% in the counselling
      groups (P=0.004). A broad support for receiving leaflets and drug counselling
      (97%) was found among attendees. Moreover, 94% of the counselling and 79% of the
      leaflets group affirmed that they received adequate information compared to 47%
      of the control (P=0.001). Counselling was found to be significantly associated
      with a much higher recall of medicine name (OR=9.6, P=0.01), how to manage missed
      doses (OR=8.9, P=0.007), and correct use of medication (OR=31.3, P<0.001).
      Leaflet use was less strongly associated than counselling and was statistically
      significant for recall regarding correct use of medication (OR=8.4, P=0.009).
      CONCLUSION: Pharmacists in a psychiatric institution can play an important role
      in satisfying patient demands for specialized information about their
      medications. Patients with depression appear very eager to receive additional
      drug information with modest difference between the written and the verbal
      counselling interventions. Patients looked at the two interventions in a very
      positive manner and no difference was observed between patients in the leaflets
      and in the counselling group with regards to how helpful, sufficient, supportive
      and reassuring was the educational material. However, both interventions were
      more informative than the control in conveying elemental drug information to
      patients. PRACTICE IMPLICATIONS: In contrast with the lack of enthusiasm that
      some clinicians express, the affirmativeness that was expressed by patients
      towards receiving written or verbal specialized educational interventions by
      pharmacists may support the psychiatric hospital pharmacists' stands in providing
      them for all patients which may aid in improving patients compliance and probably
      treatment outcome.

PMID- 18337053
TI  - What is usual about "treatment-as-usual"? Data from two multisite effectiveness
      trials.
AB  - Despite increased emphasis on broadening the implementation of empirically
      supported therapies (ESTs) to improve standard clinical practice and patient
      outcomes, objective descriptions of what actually constitutes standard practice
      in community-based drug abuse treatment do not exist. We present data from
      independent ratings of 379 audiotapes drawn from the "treatment-as-usual" arm of
      two multisite randomized effectiveness trials in the National Institute on Drug
      Abuse Clinical Trials Network. As expected, the most frequently occurring
      strategies involved assessing the participant's substance use and social
      functioning, asking open-ended questions, discussing problems and feedback, and
      giving advice and direction. However, a number of interventions associated with
      ESTs were very rarely implemented in these early sessions. These data suggest
      missed opportunities for optimally engaging patients in the early stages of
      treatment and enhancing substance use outcomes and only moderate success to date
      of efforts to bridge the gap between research and practice.

PMID- 18337054
TI  - Blending addiction research and practice: strategies for technology transfer.
AB  - Consistent with traditional conceptions of technology transfer, efforts to
      translate substance abuse and addiction research into treatment practice have
      typically relied on the passive dissemination of research findings. The large gap
      between addiction research and practice, however, indicates that there are many
      barriers to successful technology transfer and that dissemination alone is not
      sufficient to produce lasting changes in addiction treatment. To accelerate the
      translation of research into practice, the National Institute on Drug Abuse
      launched the Blending Initiative in 2001. In part a collaboration with the
      Substance Abuse and Mental Health Services Administration/Center for Substance
      Abuse Treatment's Addiction Technology Transfer Center program, this initiative
      aims to improve the development, effectiveness, and usability of evidence-based
      practices and reduce the obstacles to their timely adoption and implementation.

PMID- 18337055
TI  - Inhibition of DNA methyltransferase activity upregulates Fyn tyrosine kinase
      expression in Hut-78 T-lymphoma cells.
AB  - Tyrosine kinase Fyn, the expression of which is epigenetically regulated, has
      been proposed to be a tumour suppressor gene. A frequent deletion at the 6q
      chromosomal region encoding the Fyn gene in lymphomas has been reported.
      Therefore, we assessed the impact of 5-Aza-2'-deoxycytidine (5-dAzaC), a DNA
      methyltransferase (DNMTs) inhibitor on Fyn expression in Hut-78 T-lymphoma cells.
      Using reverse transcription, real-time quantitative PCR (RQ-PCR), and western
      blot analyses, we found that 5-dAzaC significantly increased transcript and
      protein levels of Fyn in Hut-78 T-lymphoma cells. However, bisulfite sequencing
      revealed that Hut-78 T-lymphoma cells cultured in the absence of 5-dAzaC
      contained unmethylated cytosine in the cytosine-guanosine dinucleotide island of
      the Fyn promoter. Our results suggest that the DNMTs activity may have an
      indirect influence on the expression of Fyn without altering the methylation
      level of its promoter in Hut-78 T-lymphoma cells.

PMID- 18337056
TI  - Reduction of blood lipid by berberine in hyperlipidemic patients with chronic
      hepatitis or liver cirrhosis.

PMID- 18337057
TI  - Performance of children on symptom validity tests: TOMM, MSVT, and FIT.
AB  - Symptom validity testing is a major topic in the field of neuropsychological
      research, but until now, few studies focus on effort testing in children. Three
      symptom validity tests (SVTs), the Medical Symptom Validity Test, the Test of
      Memory Malingering, and the Fifteen Item Test plus several standard
      neuropsychological tests were administered to 73 German-language school children
      from 6 to 11 years. Participants were either instructed to give full effort or to
      follow a malingering scenario. It could be demonstrated that, except for one
      child, all participants with a basic reading level of grade 2 were able to pass
      all administered SVTs according to established cutoffs for poor effort (i.e.,
      earned a score higher than the cutoff). For the experimental malingerers,
      however, it was fairly difficult to act according to the scenario throughout the
      session. While they scored worse in the neuropsychological tests, all but one of
      them failed at least one SVT. The results support the use of SVTs in childhood
      age. More elaborate experimental designs and studies with bona-fide patients and
      suspected malingerers are needed in order to evaluate both the appropriateness of
      available effort tests and the capabilities of children to fake poor performance.

PMID- 18337058
TI  - The PTSD symptom scale's latent structure: an examination of trauma-exposed
      medical patients.
AB  - Several studies have employed confirmatory factor analysis (CFA) to evaluate the
      latent structure of posttraumatic stress disorder (PTSD) assessment measures
      among various trauma-exposed populations. Findings have generally failed to
      support the current three-factor DSM-IV PTSD conceptualization, demonstrating the
      need to consider alternative models. The present study used CFA to evaluate seven
      models, including intercorrelated and hierarchical versions of two models with
      the most empirical support. Data were utilized from a heterogeneous trauma
      exposed sample of general medical patients (n=252). Based on several indices, the
      three-factor DSM-IV PTSD model was shown to be inferior to alternative models.
      The strongest support was found for an intercorrelated four-factor model,
      separating avoidance and numbing symptoms into distinct factors. Validity for
      this model was partially supported by divergent relations between factors and
      external variables. Implications of the results are discussed, and a framework is
      proposed for resolving discrepant findings in the PTSD CFA literature.

PMID- 18337059
TI  - Consumption of green tea favorably affects oxidative stress markers in weight
      trained men.
AB  - OBJECTIVE: This study investigated the effects of the consumption of green tea
      (GT) for 7 d on biomarkers of oxidative stress in young men undergoing resistance
      exercise. METHODS: Fourteen subjects performed a bench press exercise (four sets,
      10 to 4 repetitions) after undergoing a period without (control group) or with
      the intake of GT (GT group; 2 g of leaves in 200 mL of water, three times per
      day). Blood samples were obtained before and after exercise and analyzed for
      total antioxidant capacity (ferric reducing ability of plasma [FRAP]), total
      polyphenols, reduced glutathione (GSH), lipid hydroperoxide (LH) and
      thiobarbituric acid-reactive substances, creatine kinase (CK), aspartate
      aminotransferase (AST), xanthine oxidase (XO), hypoxanthine, and uric acid (UA).
      RESULTS: In the control group, exercise did not affect the values of LH,
      thiobarbituric acid-reactive substances, and FRAP, although it did reduce the
      levels of GSH (P < 0.05). In addition, exercise increased CK, AST, and XO
      activities, although it did not change the values for hypoxanthine or UA. Green
      tea reduced the postexercise concentration of LH and increased the values of
      total polyphenols, GSH, and FRAP. GT also inhibited a significant rise in CK and
      XO activities induced by exercise. Furthermore, GT decreased the AST activity and
      hypoxanthine and UA concentrations before and after exercise. The assessment of
      food consumption revealed that the participants had an unbalanced diet,
      particularly in relation to vitamin E and carotenoids. CONCLUSION: Consumption of
      GT, a beverage rich in polyphenols, may offer protection against the oxidative
      damage caused by exercise, and dietary guidance for sports participants should be
      emphasized.

PMID- 18337060
TI  - Iodine deficiency in pregnant women residing in an area with adequate iodine
      intake.
AB  - OBJECTIVE: To prevent iodine deficiency disorders, the World Health Organization,
      United Nations Children's Fund, and International Council for the Control of
      Iodine Deficiency Disorders established that for a given population median
      urinary iodine concentrations (UIC) must be 100-199 microg/L in clinically
      healthy subjects and 150-249 microg/L in clinically healthy pregnant women. We
      evaluated whether in the urban area of Rome, Italy, where a salt iodination
      program (30 mg/kg) was introduced since 2005, an increased demand of iodine
      during pregnancy is guaranteed. METHODS: During 2006, 51 pregnant women at first
      trimester of a physiologic gestation were consecutively enrolled on presentation
      to evaluate UIC in morning spot urine samples. As controls, 100 age-matched
      clinically healthy non-pregnant women were evaluated. RESULTS: The median UICs
      were 182 microg/L (range 85-340 microg/L) and 74 microg/L (range 17-243
      microg/L), respectively, in the control and pregnant groups. This difference was
      highly significant (P < 0.001). In particular, the UIC was found to be lower than
      adequate in 4% of control women compared with 92% of pregnant women. This
      difference of occurrences was highly significant (P < 0.001). CONCLUSION: This
      observational study demonstrated that, despite the adequate supplementation of
      iodine intake, most pregnant women appear not to be protected against iodine
      deficiency. If confirmed in larger case studies, this finding claims the
      attention of relevant professionals to monitor iodine nutrition during gestation,
      assuming that ordinary supplementation of iodine intake seems to be sufficient
      only in non-gestational conditions.

PMID- 18337061
TI  - The value of Allen's test in harvesting a radial forearm flap: correlation of ex
      vivo angiography and histopathological findings.
AB  - The radial forearm flap is one of the most commonly raised free flaps. In most
      cases an Allen's test is sufficient for preoperative assessment of the palmar
      arch, but an intact palmar arch does not imply that the radial artery is suitable
      for microvascular anastomosis. For a patient operated for oral squamous cell
      carcinoma, reconstruction was planned with a radial forearm flap. The flap had to
      be discarded because of advanced atherosclerosis in the presence of a negative
      Allen's test. The correlation of an ex-vivo angiography and the histopathologic
      findings was assessed. In cases of expected vascular disease, further
      examinations like color flow Doppler ultrasound are recommended to ensure
      sufficient perfusion of the radial artery.

PMID- 18337062
TI  - Aggressive osteoblastoma of the mandible.
AB  - We report a case of aggressive osteoblastoma of the mandible, an extremely rare
      primary bone tumor of the maxillofacial skeleton. Although osteoblastomas are
      benign tumors requiring only curettage for cure, there is a small subset of
      tumors that exhibit locally aggressive behavior and have atypical histopathologic
      features. Differentiation from low-grade osteosarcoma is often difficult. There
      is some disagreement as to the proper classification of these tumors. The correct
      diagnosis must be based on clinical, radiographic and pathologic features.
      Surgical resection and reconstruction is the recommended treatment for these
      invasive lesions.

PMID- 18337063
TI  - Biodegradable polymer membrane used as septal splint.
AB  - The treatment of a crooked nose is one of the most challenging rhinoplastic
      procedures. Correction of the abnormally curved or fractured septum has been
      reported using mostly scoring techniques, septoplasty and submucous resection
      techniques; cartilaginous spreader grafts can also be sutured to the distorted
      septum. Extracorporal septal straightening and repositioning/refixation is
      another useful but difficult technique. A common problem of septal cartilaginous
      grafting techniques is to harvest enough straight cartilage to correct the
      deformity. (Other donor sites such as rib cartilage are used, but harvesting
      additional cartilage is a time-consuming procedure and carries the risk of donor
      site morbidity.) Recent studies have been published using alloplastic internal
      splinting of the deformed septum. The use of poly p-dioxanone foils and porous
      polyethylene has been suggested before. In this study, a novel grafting material,
      a PolyMax membrane that has potential advantages over both materials, is
      presented. This is a porous biodegradable polymer made out of 70:30 poly(L
      lactide-co-D,L-lactide) that remains stable for at least 7 months. Poly p
      dioxanone loses its stability after only 2 months, whereas porous polyethylene is
      a permeable material that is controversial due to possible complications in cases
      of membrane exposure and infection. In this preliminary report the PolyMax
      membrane was used successfully in 3 patients.

PMID- 18337064
TI  - In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase
      inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria.
AB  - Sulfometuron methyl (SM) is an inhibitor of acetohydroxyacid synthase (AHAS), the
      first common enzyme in the branched-chain amino acid biosynthetic pathway, and
      shows activity against Mycobacterium tuberculosis both in vitro and in vivo. To
      develop AHAS inhibitor derivatives with more potent activity, 100 sulfonylurea
      analogues were screened for antimycobacterial activity against M. tuberculosis
      and non-tuberculous mycobacteria (NTM), and then evaluated for intracellular
      activity using mouse macrophages. Three new compounds with antimycobacterial
      activity comparable with that of SM were identified. These compounds exhibit
      significant activity against intracellular M. tuberculosis (including the drug
      resistant M. tuberculosis strains), and NTM Mycobacterium abscessus and
      Mycobacterium kansasii, respectively.

PMID- 18337065
TI  - Boronic acid disk tests for identification of extended-spectrum beta-lactamase
      production in clinical isolates of Enterobacteriaceae producing chromosomal AmpC
      beta-lactamases.
AB  - A study using boronic acid (BA) was designed to detect the extended-spectrum beta
      lactamases (ESBLs) in Enterobacteriaceae producing chromosomal AmpC beta
      lactamases. A total of 197 clinical isolates of Enterobacter spp. (n=100),
      Serratia marcescens (n=62) and Citrobacter freundii (n=35) were analysed. Genes
      encoding ESBLs were detected by polymerase chain reaction (PCR) amplification
      followed by direct sequencing of PCR products. The Clinical and Laboratory
      Standards Institute confirmatory test detected only 72.1% of the ESBL-producing
      isolates. When a > or =5mm increase in the zone diameter of either the
      cefotaxime/clavulanic acid and/or the ceftazidime/clavulanic acid disks tested in
      combination with BA versus cefotaxime and/or ceftazidime containing BA was
      considered to be a positive for ESBL, the method detected 60 (98.4%) of the 61
      isolates that harboured ESBLs and showed no false-positive results for ESBL-non
      producing isolates. In conclusion, the BA disk test is a highly sensitive and
      specific method for the detection of ESBLs in Enterobacteriaceae producing
      chromosomal AmpC beta-lactamases.

PMID- 18337066
TI  - Loss of Borealin/DasraB leads to defective cell proliferation, p53 accumulation
      and early embryonic lethality.
AB  - Borealin/DasraB is a member of the chromosomal passenger protein complex (CPC)
      required for proper segregation of chromosomes during mitosis. In Drosophila
      melanogaster, inactivation of Borealin/DasraB results in polyploidy, delayed
      mitosis and abnormal tissue development, indicating its critical role for cell
      proliferation. However, the in vivo role of mammalian Borealin/DasraB remains
      unclear. Here, we analyzed the expression of Borealin/DasraB and found that
      borealin is widely expressed in embryonic tissues and later restricted to adult
      tissues which relies on rapid cell proliferation. To determine the role of
      borealin during mouse development, we generated borealin-null mice through
      targeted disruption. While heterozygous mice developed normally, disruption of
      both borealin alleles resulted in early embryonic lethality by 5.5 dpc (days
      postcoitus) due to mitotic defects and apoptosis in blastocyst cells that showed
      microtubule disorganization and no CPC enrichment. At 5.5 dpc, borealin-null
      embryos exhibited excessive apoptosis and elevated expression of p53. However,
      loss of p53 did not abrogate or delay embryonic lethality, revealing that
      Borealin/DasraB inactivation triggered impaired mitosis and apoptosis though p53
      independent mechanisms. Our data show that Borealin/DasraB is essential for cell
      proliferation during early embryonic development, and its early embryonic
      lethality cannot be rescued by the loss of p53.

PMID- 18337067
TI  - Nucleotides and nucleolipids derivatives interaction effects during multi
      lamellar vesicles formation.
AB  - In this paper a micellar interface, constituted by the cationic surfactant CTAB,
      in presence of 1,2-epoxydodecane and nucleotides was used for catanionic multi
      lamellar vesicles (MLVs) formation. The micellar solution of CTAB is able to
      disperse the 1,2 epoxydodecane in the micellar core promoting the reaction of
      this reagent with the nucleotide attracted by the positive surface charge of the
      micellar aggregates. The alkylation of AMP and UMP nucleotides leads to the
      synthesis of nucleolipids. The behaviour of the supramolecular structures formed
      depends on the starting reagents (AMP, UMP and AMP+UMP) and on the assembly
      capabilities of the products. In particular nucleotides and nucleotides
      derivatives interaction effects are evaluated during the multi-lamellar vesicles
      formation. NMR spectroscopy and UV-vis measurements performed on MLVs showed
      strong aryl interactions. Interestingly, NMR spectra revealed prevailing stacking
      interactions between complementary nucleolipids. The assembly of complementary
      nucleotides affects the course of the reaction during the MLVs formation.
      Moreover the MLVs supramolecular stability has been tested by means of turbidity
      and UV-vis measurements. In particular, an enhanced stability has been found in
      systems prepared with complementary nucleotides confirming that in these systems
      the self-assembly process is influenced by nucleolipids interactions. Furthermore
      by following the hypocromic effect during the micellar catalysis, we showed that
      even in the earlier stages of the reaction significant differences are
      detectable.

PMID- 18337068
TI  - Interactions between U-937 human macrophages and tyloxapol.
AB  - Tyloxapol is reported to prevent macrophages from reacting to endotoxin. However,
      the intracellular responses that tyloxapol induces in macrophages are still not
      fully explored. Hence, the objective of this study was to evaluate the
      intracellular events in macrophages treated with tyloxapol and assess the
      antioxidant properties of tyloxapol in endotoxin-activated macrophages. Using
      flow cytometry, we examined intracellular responses in macrophages: reactive
      oxygen species (ROS) content, mitochondria membrane potential, and cell cycle
      profiles. We also assessed the antioxidant properties of tyloxapol in endotoxin
      activated macrophages. Kinetic hydrogen peroxide production tended to decline
      with increasing doses. Tyloxapol produced a progressive increase followed by a
      decline in superoxide anion production in macrophages with increasing doses.
      Tyloxapol also caused unstable fluctuations in mitochondrial membrane potential.
      Apoptosis had developed at higher doses after 4h of incubation time. After 2h of
      tyloxapol-pretreatment, tyloxapol acted as an antioxidant only at lower doses.
      Most tyloxapol-pretreated cells at lower doses fully recovered from the changes
      in superoxide anion and hydrogen peroxide production. Our findings contribute to
      a better understanding of the molecular action of tyloxapol in macrophages and
      how it protects macrophages against endotoxin.

PMID- 18337069
TI  - Biological evaluation of N-octyl-O-sulfate chitosan as a new nano-carrier of
      intravenous drugs.
AB  - An amphiphilic chitosan derivate, N-octyl-O-sulfate chitosan (NOSC) was prepared
      by octylation of amino group at C-2 position and sulfonylation at C-6 position.
      Micelle formed by NOSC has great capability in solubilization of water-insoluble
      drug paclitaxel. Enormous attention was attracted by the potential application of
      NOSC as a new drug delivery system. Tritium labeled NOSC ((3)H NOSC) was injected
      by tail vein at dose of 13.44 mg/kg in mice; kidney retained the maximum amount
      of NOSC all the time even after 24h following the injection. Pharmacokinetic
      parameters (the area under the plasma concentration-time curve, maximum plasma
      concentration, apparent plasma half-life of distribution phase and elimination
      phase, mean residence time, apparent volume of distribution, total body
      clearance) were obtained by fluorometric method in rats. The results showed a
      linear pharmacokinetics proceeding of FITC-NOSC in vivo. 75.4+/-11.6% (3)H NOSC
      of dose was excreted in urine over a 7-day period, urinary excretion was the
      predominant way of excretion of NOSC compared with bilary or fecal pathway. A
      series of safety studies consisted of acute toxicity study, intravenous
      stimulation study, injection anaphylaxis study, hemolysis study and cell
      viability assay were performed to warrant the biocompatibility of the NOSC as
      intravenous materials. The LD(50) value of NOSC administrated by i.v. and i.p.
      were calculated as 102.59 and 130.53 mg/kg, respectively. No intravenous
      stimulation, injection anaphylaxis, hemolysis and cytotoxicity were observed in
      the safety studies. The tissue distribution, pharmacokinetics, excretion and
      safety study were persuasive for the potential application of NOSC as a new drug
      carrier.

PMID- 18337070
TI  - Pharmacokinetics of a C5a receptor antagonist in the rat after different sites of
      enteral administration.
AB  - Pharmacokinetics of the orally active, cyclic peptide complement factor C5a
      receptor antagonist, AcF-[OP(D-Cha)WR] (PMX53) were determined in the rat.
      Biliary excretion of the unchanged drug was a major route of elimination after
      intravenous administration, but not following oral administration. Portal and
      peripheral blood levels of PMX53 were determined after oral administration or
      direct injection into the ileum, colon or local administration into the rectum.
      PMX53 was rapidly absorbed from mucosal sites, with peak plasma levels occurring
      as early as 5 min post-administration. Early portal blood levels were
      consistently higher than peripheral levels following ileal, colonic and rectal
      administration, but not after oral dosing. The results suggest that hepatic
      elimination occurs rapidly with higher (>or= 100 ng/ml) peripheral blood levels
      of the drug. Combination of PMX53 with the excipient chitosan resulted in
      significantly higher peripheral levels of the drug following ileal and colonic
      application, but not with buccal or oral administration. Buccal administration
      resulted in a similar plasma pharmacokinetic profile to oral administration.
      These results suggest that PMX53 is rapidly absorbed across mucosal membranes in
      the rat, and that administration using excipients such as chitosan may offer a
      method of increasing bioavailability.

PMID- 18337071
TI  - [Early neonatal bacterial infections: could superficial bacteriologic samples at
      birth be limited?].
AB  - INTRODUCTION: Without promptly started antibiotic therapy, early neonatal
      bacterial infections incur a significant mortality. Superficial bacteriologic
      samples at birth have in France a real place for the diagnosis and the decision
      to treat a neonate. OBJECTIVES: In order to limit their indication and their
      choice, the aim of this article was to describe the proportion of neonates with
      samples and to determine the diagnostic value of the gastric aspirate, the ear
      swab and the placental sample. METHODS: Neonates born in the CHRU of Lille in
      2005 and staying in the maternity ward were prospectively included. Criteria for
      samples, type of samples and diagnosis taken were noted. Sensibility,
      specificity, positive and negative predictive values and likelihood ratios for a
      positive test and a negative test were calculated. RESULTS AND CONCLUSION: This
      study included 3918 neonates; 1.7% (65 children) were infected according to our
      criteria; 42.3% received bacteriologic samples. In accordance with the Anaes
      guidelines (2002), if mothers were Group B Streptococci positive and received
      intrapartum antibiotics (up to 2 injections) or did not have any screening test
      without any other indication of samples, the neonate did not have to receive
      bacteriologic samples. The gastric aspirate was the best exam thanks to the
      excellent negative predictive value of its direct examination: 99.4% (IC 95%:
      98.8-99.7), its high likelihood ratio for a positive test: 10.04 (IC 95%: 8.29
      12.15) and its low likelihood ratio for a negative test: 0.16 (IC 95%: 0.09
      0.29); this sample could restrict the antibiotics' ratio given to the neonate.
      Placental sample could be taken only in certain indications.

PMID- 18337072
TI  - The Mediterranean Adequacy Index: further confirming results of validity.
AB  - BACKGROUND AND AIMS: Since dietary patterns can influence levels of major risk
      factors for chronic disease, various indexes or scores of overall diet quality
      have been proposed and related to risk factors for disease. The Mediterranean
      Adequacy Index (MAI) was developed to simply assess how close a diet is to the
      Healthy Reference National Mediterranean Diet (HRNMD), a healthful diet in which
      Mediterranean food patterns are inversely correlated with prevalence of risk
      factors for chronic disease. This report describes further evidence of MAI values
      for diets of population groups from different countries. METHODS AND RESULTS: MAI
      is obtained by dividing the food group intakes typical of a healthy reference
      Mediterranean diet, expressed in g/day, by the food group intakes not
      characteristic of a healthy Mediterranean diet. In this paper, the MAI was
      computed based on the diets of 23 population groups from Italy, Greece, U.S.A.,
      Costa Rica, Chile, Spain, and Germany. High MAI values were recorded among
      working class men from southern Italy, and Seven Countries Study (SCS) men from
      the Greek islands, and the lowest among U.S.A. men and a control group of German
      women; surprisingly low values were recorded among Madrid men and women and
      participants from Spanish-speaking Latin American countries. The inversely
      significant correlation between the 16 SCS cohort diet MAI values and the 25-year
      coronary heart disease death rate previously observed was stable when an
      appropriate statistical analysis was used. Furthermore, MAI values of diets in
      elderly participants from 10 European countries followed for 10 years were
      inversely associated with total mortality. CONCLUSIONS: The above results further
      confirm the validity of MAI, indicating that it is as good as the most utilised
      indexes or scores proposed for adults in Europe.

PMID- 18337073
TI  - Determination and pharmacokinetic study of indirubin in rat plasma by high
      performance liquid chromatography.
AB  - A specific, simple and sensitive HPLC method with UV detection was developed and
      validated for the pharmacokinetic studies of indirubin in rat plasma for the
      first time. Indirubin, with osthole as the internal standard, was extracted from
      plasma samples by liquid-liquid extraction. Chromatographic separation was
      conducted on a reverse-phase ODS column (200 mm x 4.6 mm, i.d., 5 microm), using
      a mixture of methanol-water (75:25, v/v) as the mobile phase at a flow rate of
      1.0 ml/min with UV detection at 289 nm. The calibration curve of indirubin was
      linear over the range of 6.5-1950 ng/ml in rat plasma. The lower limit of
      quantification (LLOQ) was found to be 6.5 ng/ml. The present method was
      successfully applied for estimating the pharmacokinetic parameters of indirubin
      following intravenous and intraperitoneal administration of indirubin to rats.

PMID- 18337074
TI  - Anti-hepatitis B virus activities of triterpenoid saponin compound from
      Potentilla anserine L.
AB  - The Tibetan herb Potentilla anserina L. has been widely used in China for many
      thousands of years to treat hepatitis-B. Bioassay-guided fractionation of the
      ethanol extract of the rhizomes led to the isolation of a triterpenoid saponin
      (TS) that was determined to be 2alpha,3beta,19alpha-trihydroxyurs-12-en-28-oic
      acid beta-D-glucopyranosyl ester. Using models of HBV infection, this compound
      was evaluated for its effect on HBV antigene expression in the 2.2.15 cell line
      in vitro and anti-hepatitis B virus (HBV) activities in Peking ducklings in vivo.
      Results showed that it could decrease the expression levels of HBsAg, HBeAg and
      HBVDNA in the 2.2.15 cell culture and the inhibitory effect was not due to the
      cytotoxity of the triterpenoid saponin. The antiviral study in vivo on Peking
      ducklings also demonstrated that this compound inhibits duck hepatitis B virus
      (DHBV) DNA replication.

PMID- 18337075
TI  - In vitro antiplasmodial activity of extract and constituents from Esenbeckia
      febrifuga, a plant traditionally used to treat malaria in the Brazilian Amazon.
AB  - Esenbeckia febrifuga (Rutaceae) is a plant traditionally used to treat malaria in
      the Brazilian Amazon region. Ethanol extract of stems displayed a good
      antiplasmodial activity against Plasmodium falciparum strains W-2 (IC(50) 15.5+/
      0.71 microg/ml) and 3 D7 (IC(50) 21.0+/-1.4 microg/ml). Two coumarins (bergaptene
      1 and isopimpinellin 2), five alkaloids (flindersiamine 3, kokusaginine 4,
      skimmiamine 5, gamma-fagarine 6 and 1-hydroxy-3-methoxy-N-methylacridone, 7),
      besides a limonoid (rutaevine 8), have been isolated for the first time from this
      species. Antiplasmodial activity of compounds 3, 5-8 has been evaluated in vitro
      against P. falciparum strains (W-2 and 3D7) and the furoquinolines 5 and 6 were
      the most potent displaying IC(50) values <50 microg/ml; flindersiamine (3) showed
      a weak activity while alkaloid 7 and rutaevine (8) were inactive (IC(50)>100
      microg/ml).

PMID- 18337076
TI  - Chain-length dependence of the kinetics of the hyaluronan hydrolysis catalyzed by
      bovine testicular hyaluronidase.
AB  - Hyaluronan (HA) has various biological functions that are strongly dependent on
      its chain length. In some cases, as in inflammation and angiogenesis, long and
      short chain-size HA effects are antagonistic. HA hydrolysis catalyzed by
      hyaluronidase (HAase) is believed to be involved in the control of the balance
      between longer and shorter HA chains. Our studies of native HA hydrolysis
      catalyzed by bovine testicular HAase have suggested that the kinetic parameters
      depend on the chain size. We thus used HA fragments with a molar mass ranging
      from 8x10(2) g mol(-1) to 2.5x10(5) g mol(-1) and native HA to study the
      influence of the chain length of HA on the kinetics of its HAase-catalyzed
      hydrolysis. The initial hydrolysis rate strongly varied with HA chain length.
      According to the Km and Vm/Km values, the ability of HA chains to form an
      efficient enzyme-substrate complex is maximum for HA molar masses ranging from
      3x10(3) to 2x10(4) g mol(-1). Shorter HA chains seem to be too short to form a
      stable complex and longer HA chains encounter difficulties in forming a complex,
      probably because of steric hindrance. The hydrolysis Vm values strongly suggest
      that as the chain length decreases the HAase increasingly catalyses
      transglycosylation rather than hydrolysis. Finally, two HA chain populations,
      corresponding to HA chain molar masses lower and higher than approximately
      2x10(4) g mol(-1), are identified and related to the bi-exponential character of
      the model we have previously proposed to fit the experimental points of the
      kinetic curves.

PMID- 18337077
TI  - Predictors of poor attendance at an outpatient pulmonary rehabilitation
      programme.
AB  - BACKGROUND: Pulmonary rehabilitation (PR) is recommended for patients with
      respiratory disease who feel limited by breathlessness. Poor attendance wastes
      finite resources, increases waiting times and is probably associated with poorer
      clinical outcomes. We investigated what factors, identifiable from routine
      hospital data, predict poor attendance once enrolled in a pulmonary
      rehabilitation programme (PRP). METHODS: Retrospective case note study of 239
      patients (60% male) of mean (S.D.) age of 66.6 (8.7) years, mean FEV(1) 39.6
      (14.6)% predicted, who attended a 6 (short) or 18 (long) week, 18 session,
      outpatient PRP. Attendance data was analysed using linear multiple regression
      analysis with the log transformed odds ratio of attendance as the dependant
      variable. RESULTS: Overall median attendance was 16 out of 18 sessions. Being a
      current smoker (p<0.05), attending a long PRP (p<0.05), more previous hospital
      admissions (p<0.01), higher Medical Research Council (MRC) dyspnoea score
      (p<0.01) or enduring a long journey (p<0.001) were independent risk factors for
      low attendance. Lower body mass index (BMI) and distance from PR centre were of
      borderline importance (p<0.1) but age, gender, co-morbidity, respiratory
      diagnosis, FEV(1) and St. Georges Respiratory Questionnaire Score at baseline did
      not predict later attendance (p>0.2). CONCLUSIONS: Attendance at PRPs is
      independently influenced by smoking status, the degree of breathlessness,
      frequency of hospital admissions, length of the programme and journey time.

PMID- 18337078
TI  - Assembly and biological role of podosomes and invadopodia.
AB  - Regulated tissue invasion via motile and lytic events is critical for
      physiological processes such as immune system function and inflammatory
      responses, wound healing, and organ development, but pathological subversion of
      this process drives tumour cell invasion and metastasis. Cell migration and
      invasion require the integration of several processes that include: first, the
      local modulation of cytoskeleton structure and contractile forces; second, the
      turnover of substrate adhesions and their associated microfilaments; and third,
      the generation of specialised, transient domains that mediate the protease
      dependent focal degradation of the extracellular matrix. Recent work has re
      discovered prominent actin-based cellular structures, termed invadopodia and
      podosomes, as unique structural and functional modules through which major
      invasive mechanisms are regulated. The stage is now set to unravel their roles in
      the physiology and pathology of tissue plasticity and repair.

PMID- 18337079
TI  - Quantitative electrochemiluminescence detection of proteins: Avidin-based sensor
      and tris(2,2'-bipyridine) ruthenium(II) label.
AB  - Quantitative electrochemiluminescence (ECL) detection of a model protein, bovine
      serum albumin (BSA) was achieved via biotin-avidin interaction using an avidin
      based sensor and a well-developed ECL system of tris(2,2'-bipyridine)
      ruthenium(II) derivative as label and tri-n-propylamine (TPA) as coreactant. To
      detect the protein, avidin was linked to the glassy carbon electrode through
      passive adsorptions and covalent interaction with carboxylate-terminated carbon
      nanotubes that was used as binder to immobilize avidin onto the electrode. Then,
      biotinylated BSA tagged with tris(2,2'-bipyridine) ruthenium(II) label was
      attached to the prepared avidin surface. After binding of BSA labeled with
      tris(2,2'-bipyridine) ruthenium(II) derivative to the surface-immobilized avidin
      through biotin, ECL response was generated when the self-assembled modified
      electrode was immersed in a TPA-containing electrolyte solution. Such double
      protein labeling protocol with a biotin label for biorecognition and ruthenium
      label for ECL detection facilitated the detection of protein compared to the
      classical double antibody sandwich format. The ECL intensity was linearly
      proportional to the feed concentration of BSA over two orders of magnitude in the
      range of 15nM to 7.5microM. The detection limit was estimated to be 1.5nM.
      Further application to the lysozyme analysis was carried out to validate the
      present approach for an effective and favorable protocol for the quantitative
      detection of proteins. The dynamic range of lysozyme was from 0.001gL(-1) to
      0.1gL(-1) and the detection limit was 0.1mgL(-1). Electrochemical impedance and
      cyclic voltammetric measurements along with some necessary control experiments
      were conducted to characterize the successful formation of self-assembled
      modified electrodes and to grant the whole detection process.

PMID- 18337080
TI  - Quantitative oligonucleotide microarray data analysis with an artificial standard
      probe strategy.
AB  - Quantitative data analysis is an important element in several applications of DNA
      microarray, including mRNA expression profiling and estimation of infectious
      doses for pathogens. Here, we introduce an artificial standard probe strategy for
      quantitative pathogen detection using an oligonucleotide chip as a model system.
      The standard capture probe sequence was artificially designed to prevent non
      specific hybridization with bacterial targets. Based on the fluorescence
      intensities of artificial standard spots, the raw fluorescence intensity data for
      specific spots could be corrected to generate linear correlations with target
      concentrations. Therefore, our novel artificial standard probe may be effectively
      applied for the correction of chip-to-chip variations and quantitative data
      analysis of a one-color labeled DNA microarray system.

PMID- 18337081
TI  - Recent advances in metastasis research.
AB  - Advances in the early prediction, detection, and treatment of metastatic disease
      has improved the outlook in cancer patients in recent decades, however,
      metastasis remains the major cause of death in affected individuals. Metastasis
      occurs in a series of discreet biological steps in which a single, frequently
      clinically occult micrometastatic cell travels from the primary tumor to a
      distant location, where it lodges, grows, and ultimately results in the patient's
      death. Recent work has provided many new insights in the mechanisms and biology
      behind metastatic spread. This short review surveys some of the most important
      recent developments that have helped increase our understanding of the three
      broad phases of metastasis - the genesis of the metastatic cell through the loss
      of local constraints in the primary tumor microenvironment, dissemination of the
      cell to a distant organ while avoiding immune surveillance, and finally lodging
      and growth of the overt metastasis. These studies are providing mounting evidence
      that the interactions between tumor and normal cells and tissues are critical for
      disease progression - a paradigm that will provide a fertile area for future
      research.

PMID- 18337082
TI  - Population epigenetics.
AB  - Our knowledge of the mechanisms that specify and propagate epigenetic states of
      gene expression is expanding rapidly; however, the significance of variation in
      epigenetic states at the population level remains largely unexplored. Population
      epigenetics, emerging as an active subfield at the interface of molecular
      genetics, genomics, and population biology, addresses questions concerning the
      prevalence and importance of epigenetic variation in the natural world.

PMID- 18337084
TI  - Precision grasping in humans: from motor control to cognition.
AB  - In the past decade, functional neuroimaging has proved extremely useful in
      mapping the human motor circuits involved in skilled hand movements. However, one
      major drawback of this approach is the impossibility to determine the exact
      contribution of each individual cortical area to precision grasping. Because
      transcranial magnetic stimulation (TMS) makes it possible to induce a transient
      'virtual' lesion of discrete brain regions in healthy subjects, it has been
      extensively used to provide direct insight into the causal role of a given area
      in human motor behaviour. Recent TMS studies have allowed us to determine the
      specific contribution, as well as the timing and the hemispheric lateralisation,
      of distinct parietal and frontal areas to the control of both the kinematics and
      dynamics of precision grasping. Moreover, recent researches have shown that the
      same cortical network may contribute to language and number processing,
      supporting the existence of tight interactions between processes involved in
      cognition and actions. The aim of this paper is to offer a concise overview of
      recent studies that have investigated the neural correlates of precision grasping
      and the possible contribution of the motor system to higher cognitive functions
      such as language and number processing.

PMID- 18337083
TI  - siRNA and miRNA processing: new functions for Cajal bodies.
AB  - In diverse eukaryotes, micro-RNAs (miRNAs) and small interfering RNAs (siRNAs)
      regulate important processes that include mRNA inactivation, viral defense,
      chromatin modification, and transposon silencing. Recently, nucleolus-associated
      Cajal bodies in plants have been implicated as sites of siRNA and miRNA
      biogenesis, whereas in animals siRNA and miRNA dicing occurs in the cytoplasm.
      The plant nucleolus also contains proteins of the nonsense-mediated mRNA decay
      pathway that in animals are found associated with cytoplasmic processing bodies
      (P-bodies). P-bodies also function in the degradation of mRNAs subjected to miRNA
      and siRNA targeting. Collectively, these observations suggest interesting
      variations in the way siRNAs and miRNAs can accomplish their similar functions in
      plants and animals.

PMID- 18337085
TI  - Molecular mapping of human hepatocellular carcinoma provides deeper biological
      insight from genomic data.
AB  - DNA microarray analysis of human cancer has resulted in considerable accumulation
      of global gene profiles. However, extraction and understanding the underlying
      biology of cancer progression remains a significant challenge. This study applied
      a novel integrative computational and analytical approach to this challenge in
      human hepatocellular carcinoma (HCC) with the aim of identifying potential
      molecular markers or novel therapeutic targets. We analysed 100 HCC tissue
      samples by human 30K DNA microarray. The gene expression data were uploaded into
      the network analysis tool, and the biological networks were displayed
      graphically. We identified several activated 'hotspot' regions harbouring a
      concentration of upregulated genes. Several 'hotspot' regions revealed integrin
      and Akt/NF-kappaB signalling. We identified key members linked to these
      signalling pathways including osteopontin (SPP1), glypican-3 (GPC3), annexin 2
      (ANXA2), S100A10 and vimentin (VIM). Our integrative approach should
      significantly enhance the power of microarray data in identifying novel potential
      targets in human cancer.

PMID- 18337086
TI  - Managing cancer in the EU: the Organisation of European Cancer Institutes (OECI).
AB  - Organization of European Cancer Institutes (OECI) has the mission to facilitate
      the development of European comprehensive cancer centres by integrating care and
      prevention with research and education. Core issues are to deliver a complete
      multidisciplinary care of high quality and stimulate translational cancer
      research. The goal is to innovate the cancer care. The increasing problem of
      critical mass will be solved by networking comprehensive cancer centres
      containing quality assured harmonized infrastructures. This will give Europe a
      new potential to extend the cancer research to areas not possible to cover by
      single centres.

PMID- 18337087
TI  - The efficacy of treatment schedules according to Barcelona Clinic Liver Cancer
      staging for hepatocellular carcinoma - Survival analysis of 3892 patients.
AB  - The Barcelona Clinic Liver Cancer (BCLC) staging offers prognostic stratification
      and treatment allocation for hepatocellular carcinoma (HCC). We conducted this
      retrospective study to assess the efficacy of different treatment options for
      patients with initial HCC diagnosis. Survival rate and median survival times
      associated with different treatment options in each stage of BCLC classification
      were compared using the Kaplan-Meier method and log-rank test. A total of 3892
      patients were enrolled. Overall survival rates were 46.2% at 1 year and 16.6% at
      5 years. The median survival times decreased from 57.7 months in very early stage
      to 1.6 months in terminal stage. Surgical resection offered the best survival
      benefit for patients in very early, early and even intermediate stages.
      Transarterial embolisation and conformal radiotherapy offered survival benefits
      for selected patients in advanced and terminal stages. In conclusion, following
      the treatment schedules allocated by BCLC staging had survival benefits for HCC
      patients.

PMID- 18337088
TI  - The generally accepted version of steroidogenesis is not free of uncertainties:
      other tenable and possibly superior renditions may be invented.

PMID- 18337089
TI  - Role of the insulin-like growth factor system on an estrogen-dependent cancer
      phenotype in the MCF-7 human breast cancer cell line.
AB  - We previously established that exposure of the estrogen receptor (ER) alpha
      positive MCF-7 human breast cancer cell line to 17-beta-estradiol (E2) results in
      the post-confluent development of multilayered cellular aggregates (foci) which
      is consistent with the in vivo cancer phenotype of uncontrolled cellular
      proliferation. In this investigation, the interaction between the insulin-like
      growth factor receptor (IGF-IR) and ER-signaling systems in regard to post
      confluent focus development was studied. We demonstrated that focus development
      requires the presence of E2 and insulin-like growth factor I (IGF-I) or insulin
      like growth factor II (IGF-II), as well as intact ER and IGF-IR. Focus
      development in MCF-7 cultures, which occurs only after formation of a confluent
      monolayer, coincides with E2 regulation of key members of the IGF-signaling
      system such as IGF-IR, IGF-II, insulin receptor substrate 1 (IRS-1), and insulin
      like growth factor binding protein 3 (IGFBP-3), as demonstrated by real-time
      polymerase chain reaction (PCR). To establish the relevancy of an intact IGF
      signaling system for foci formation, we generated stable clones from MCF-7 with
      IGF-IR suppressed by siRNA. Results from these studies implicate signaling
      through the IGF-IR to be an integral requirement for E2-dependent post-confluent
      proliferation and focus formation. In summary, these studies establish the
      interactive roles of IGFs and E2 in the post-confluent development of foci, and
      will allow subsequent identification of targets for therapeutic intervention in
      the control and treatment of estrogen-dependent breast cancer.

PMID- 18337090
TI  - Estrone sulfate (E1S), a prognosis marker for tumor aggressiveness in prostate
      cancer (PCa).
AB  - Seeking insight into the possible role of estrogens in prostate cancer (PCa)
      evolution, we assayed serum E2, estrone (E1), and estrone sulfate (E1S) in 349
      PCa and 100 benign prostatic hyperplasia (BPH) patients, and in 208 control
      subjects in the same age range (50-74 years). E1 (pmol/L+/-S.D.) and E1S
      (nmol/L+/-S.D.) in the PCa and BPH patients (respectively 126.1+/-66.1 and 2.82+/
      1.78, and 127.8+/-56.4 and 2.78+/-2.12) were significantly higher than in the
      controls (113.8+/-47.6 and 2.11+/-0.96). E2 was not significantly different among
      the PCa, BPH, and control groups. These assays were also carried out in PCa
      patients after partition by prognosis (PSA, Gleason score (GS), histological
      stage, and surgical margins (SM)). Significantly higher E1S levels were found in
      PCa with: PSA>10 ng/L (3.05+/-1.92) versus PSA<or=10 ng/mL (2.60+/-1.55), stage
      pT3-T4 (2.99+/-1.80) versus pT2 (2.58+/-1.58), and positive (3.26+/-1.95) versus
      negative margins (2.52+/-1.48). E1 was higher in poor- than in better-prognosis
      PCa. E2 was significantly higher in PCa with GS>or=4+3 (109.5+/-43.8) versus
      GS<or=3+4 (100.6+/-36.5) and increased significantly when GS increased from 3+3
      to 4+4. Estrogens, especially E1S appeared to be possible markers of PCa
      progression. Attempting to identify potential sources of E2 in PCa according to
      prognosis, as well as in BPH, we found a significant correlation coefficient
      between E1S and E2 (0.266-0.347) in poor-prognosis PCa and no correlation in BPH
      (0.026) and better-prognosis PCa (0.013-0.104). It is as though during
      progression of PCa from good to poor prognosis there were a shift in the E1 to E2
      metabolic pathway from predominantly oxidative to predominantly reductive.

PMID- 18337091
TI  - Improved tensile strength of glycerol-plasticized gluten bioplastic containing
      hydrophobic liquids.
AB  - The aim of the present work has been to study the influence of hydrophobic
      liquids on the morphology and the properties of thermo-molded plastics based on
      glycerol-plasticized wheat gluten (WG). While the total amount of castor oil and
      glycerol was remained constant at 30 wt%, castor oil with various proportions
      with respect to glycerol was incorporated with WG by mixing at room temperature
      and the resultant mixtures were thermo-molded at 120 degrees C to prepare sheet
      samples. Moisture absorption, morphology, dynamic mechanical properties, and
      tensile properties (Young's modulus, tensile strength and elongation at break) of
      the plastics were evaluated. Experimental results showed that the physical
      properties of WG plastic were closely related to glycerol to castor oil ratio.
      Increasing in castor oil content reduces the moisture absorption markedly, which
      is accompanied with a significant improvement in tensile strength and Young's
      modulus. These observations were further confirmed in 24 wt% glycerol-plasticized
      WG plastics containing 6 wt% silicone oil or polydimethylsiloxane (PDMS) liquid
      rubber.

PMID- 18337092
TI  - Olive mill wastewater stabilization in open-air ponds: impact on clay-sandy soil.
AB  - The aim of this work was to study the natural biodegradation of the stored olive
      mill wastewater (OMW) in ponds and the infiltration as well as the impact on soil
      of the effluent in the evaporation pond used for the storage over the past eight
      years. For this, two approaches were considered. First, a laboratory-scale column
      was used for the infiltration of OMW through soil (clay and sand) to predict the
      effect of the clayey soil in reducing OMW pollution. Second, the ponds including
      the effluent annually stored and having this clayey structure were investigated.
      At the laboratory-scale, a modification of OMW contents was noticed, with the
      elimination of 95% of total suspended solids (TSS), 60% of chemical oxygen demand
      (COD), 40% of total organic carbon (TOC), 50% of total P, 50% of phenols and 40%
      of minerals (K+, Mg++ and Na+). The experimented soil was able to restrain the
      considerable effects of OMW pollution. In the ponds, the granulometric
      characteristics, the physico-chemical and the biological parameters of the soil
      profile from the contaminated pond were compared to those of a control soil,
      located near the contaminated pond. Property modifications of the contaminated
      soil were noted, especially pH, electrical conductivity, COD and microflora.
      These changes can be explained by the infiltration of OMW constituents, which
      were noticed in the soil layers, especially phenolic compounds that have a
      negative effect on the ground water.

PMID- 18337093
TI  - Identification and degradation characterization of hexachlorobutadiene degrading
      strain Serratia marcescens HL1.
AB  - A bacterium (strain HL1) capable of growing with hexachlorobutadiene (HCBD) as
      sole carbon and energy sources was isolated from a mixture of soil contaminated
      with HCBD and activated sludge obtained from petrochemical plant wastewater
      treatment plant by using enrichment culture. Biochemical characteristics and
      phylogenetic analysis based on 16S rDNA sequence indicate that strain HL1 clearly
      belongs to Serratia marcescens sp. Resting cells of strain HL1 were found to
      remove HCBD from culture fluids with the concomitant release of chloride ion
      under aerobic conditions. The ranges of pH value and temperature for satisfactory
      growth of strain HL1 cells were from 7.0 to 8.0 and 25 to 30 degrees C,
      respectively. Capability of resting cells to degrade HCBD was induced by HCBD in
      the culture fluids. HCBD (20mg/l) was removed from culture fluids by resting
      cells in 4 d without lag phase, but for 50mg/l and 80mg/l HCBD 7 days were needed
      with lag phase. Growth of strain HL1 cells was inhibited by HCBD at the
      concentration up to 160mg/l. First order kinetics could be fitted to the
      biodegradation of HCBD by HL1 cells after lag phase at initial concentrations of
      20, 50, and 80mg/l. Strain HL1 also showed strong capacity to degrade
      chloroprene, trichloroethylene, tetrachloroethylene, and vinyl chloride at solely
      initial concentration of 50mg/l. Results could offer useful information for the
      application of strain HL1 in bioremediation or control of HCBD-polluted
      environment.

PMID- 18337094
TI  - A novel cholic acid-based contrast enhancement agent for targeted MRI.
AB  - The novel Gd(III) complexes of heptadentate ligands NE3TA and NE3TA-Bn were
      prepared, and their relaxivities were measured and favorably compared to the
      commercially available MRI contrast enhancement agent Gd(DOTA). NE3TA was
      conjugated with cholic acid (CA) to produce CA-NE3TA. TEM images of Gd(CA-NE3TA)
      indicate that the complex self-assembles forming nano-sized micelles and displays
      an over threefold increased relaxivity compared to Gd(DOTA). The new cholic acid
      conjugated nanoparticle MR contrast enhancement agent, Gd(CA-NE3TA) possesses
      great promise for use in targeted MRI.

PMID- 18337095
TI  - Aryl-indolyl maleimides as inhibitors of CaMKIIdelta. Part 3: Importance of the
      indole orientation.
AB  - A family of aryl-substituted maleimides was prepared and studied for their
      activity against calmodulin dependant kinase. Inhibitory activities against the
      enzyme ranged from 10nM to >20microM and were dependant upon both the nature of
      the aryl group and the tether joining the basic amine to the indolyl maleimide
      core of the inhibitors. Key interactions with the kinase ATP site and hinge
      region, predicted by homology modeling, were confirmed.

PMID- 18337096
TI  - Tetrazole-biarylpyrazole derivatives as cannabinoid CB1 receptor antagonists.
AB  - Cannabinoid CB1 receptors have been the focus of extensive studies since the
      first clinical results of rimonabant (SR141716) for the treatment of obesity and
      related metabolic disorders were reported in 2001. To further evaluate the
      properties of CB receptors, we have designed a new series of tetrazole
      biarylpyrazoles. The various analogues were efficiently prepared and bio-assayed
      for binding to cannabinoid CB1 receptor. Six of the new compounds which displayed
      high in vitro CB1 binding affinities were assayed for binding to CB2 receptor.
      Noticeably, cyclopentyl-tetrazole (9a) demonstrated good binding affinity and
      selectivity for CB1 receptor (IC(50)=11.6nM and CB2/CB1=366).

PMID- 18337097
TI  - Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor
      CXCR3.
AB  - Modification of a 2-iminobenzimidazole series derived from an HTS hit resulted in
      compounds with improved in-vitro species selectivity. Incorporation of an 8
      quinoline amide and conformational rigidification of an aliphatic tether
      furnished potent compounds suitable for further lead optimization.

PMID- 18337098
TI  - Muscle MRI findings in patients with an apparently exclusive cardiac phenotype
      due to a novel LMNA gene mutation.
AB  - The case of a family in which several members displayed conduction defects
      inherited as a dominant trait is reported. The proband was a young woman with a
      1st degree atrio-ventricular block and high serum creatine kinase. Several
      members of the family featured cardiologic symptoms. All adult family members
      were clinically evaluated and blood tests including serum creatine-kinase levels,
      standard and Holter ECG, echocardiogram and muscle MRI were performed. LMNA gene
      analysis was carried out and a novel missense mutation consisting in substitution
      of exon 4 c.799 T/C, p.Tyr267His was revealed. The mutation was present in seven
      family members, five of whom displayed cardiac defects alone with no involvement
      of the skeletal muscle. In all mutated individuals muscle MRI featured a pattern
      of skeletal muscle involvement similar to that observed in autosomal dominant
      Emery Dreifuss muscular dystrophy, suggesting that even patients bearing a LMNA
      gene mutation associated to an apparently selective cardiac phenotype may present
      subclinical skeletal muscle involvement.

PMID- 18337099
TI  - Familial aggregation of white matter lesions in myotonic dystrophy type 1.
AB  - This study aimed to determine whether white matter lesions, previously described
      as a frequent feature in myotonic dystrophy type 1 (DM1), aggregate within DM1
      families or are sporadic findings, and to explore the relationship between these
      lesions and clinical or genetic features. Brain MRI of 60 DM1 patients belonging
      to 22 families were evaluated and white matter lesions were rated according to a
      semiquantitative method. Presence and extent of lobar, temporal or
      periventricular lesions showed a significant association with the family history
      of lesions and the disease duration, and no association with the CTG repeat size.
      Furthermore, parent-offspring and sibling pairs showed a significant positive
      concordance for lesion severity. White matter lesions demonstrate familial
      aggregation in DM1 and no relationship with CTG repeat length. These findings
      suggest that other genetic causes and/or unknown environmental factors influence
      the occurrence and severity of lesions in patients carrying the DM1 genetic
      defect.

PMID- 18337100
TI  - Clinical, electrophysiologic, and genetic study of non-dystrophic myotonia in
      French-Canadians.
AB  - Thirty-three French-Canadian families with non-dystrophic myotonia were
      identified. Fifty subjects were recruited and submitted to a complete clinical,
      electrophysiologic and genetic evaluation. Thirteen mutations were identified in
      CLCN1 and five mutations were identified in SCN4A. Onset in the lower
      extremities, presence of tongue myotonia and transient weakness suggested
      recessive CLCN1 mutations. Lid myotonia, absence of hypertrophy and exacerbation
      with cold temperature suggested SCN4A mutations. Pain was not a feature of
      dominant CLCN1 mutations while it could be seen in the others, more frequently in
      SCN4A mutations. Warm up phenomenon, hand grip myotonia, percussion myotonia, lid
      lag and hormonal effects were not distinguishing features. Repetitive nerve
      stimulation and short exercise test showed either a large (>50%) or mild-moderate
      (10-50%) decrement with recessive CLCN1 mutations while they showed only mild or
      no decrement with dominant CLCN1 and SCN4A mutations. The French-Canadian
      population shows wide phenotypic and genotypic heterogeneity in non-dystrophic
      myotonias.

PMID- 18337101
TI  - A patient with both Charcot-Marie-Tooth disease (CMT 1A) and mild spinal muscular
      atrophy (SMA 3).
AB  - In the present study, we report a single Polish SMA family in which the 17p11.2
      p12 duplication causative for the Charcot-Marie-Tooth type 1A disease (CMT1A) was
      found in addition to a deletion of exons 7 and 8 of the SMN1 gene. A patient
      harboring both SMA and CMT1A mutations manifested with SMA3 phenotype and foot
      deformity. Her electrophysiological testing showed chronic neurogenic changes in
      proximal muscles that are typical for SMA, but also slowed conduction velocity in
      motor and sensory fibers that is typical for demyelinating neuropathy.

PMID- 18337102
TI  - Influence of light handrail use on the biomechanics of stair negotiation in old
      age.
AB  - The high incidence of falls in older adults during stair negotiation suggests
      that this task is physically challenging and potentially dangerous. The present
      study aimed to examine the influence of light handrail use on the biomechanics of
      stair negotiation in old age. Thirteen older adults ascended and descended a
      purpose-built staircase at their self-selected speed: (i) unaided and (ii) with
      light use of the handrails. Ground reaction forces (GRFs) were measured from
      force platforms mounted into each step and motion capture was used to collect
      kinematic data. Knee and ankle joint moments were calculated using the kinetic
      and kinematic data. The horizontal separation between the centre of mass (COM)
      and the centre of pressure (COP) was assessed in the sagittal and frontal planes.
      During stair ascent, handrail use caused a different strategy to be employed
      compared to unaided ascent with a redistribution of joint moments. Specifically,
      the ankle joint moment (of the trailing leg) was reduced with handrail use, which
      has previously been shown to approach its limits during unaided stair ascent, but
      the knee joint moment (of the leading leg) increased. Previous research has shown
      that a larger joint moment reserve is available at the knee during unaided stair
      ascent. During stair descent, the ankle joint moment increased with handrail use,
      this was associated, however, with a more effective control of balance as shown
      by a reduced COM-COP separation in the direction of progression compared to
      unaided descent. These results indicate that although the biomechanical
      mechanisms are different for stair ascent and descent, the safety of stair
      negotiation is improved for older adults with light use of the handrails.

PMID- 18337103
TI  - The effect of foot type on in-shoe plantar pressure during walking and running.
AB  - The purpose of this study was to determine if low arch feet have altered plantar
      loading patterns when compared to normal feet during both walking and running.
      Fifty healthy subjects (34 normal feet, 16 flat feet) walked and ran five trials
      each at standard speeds. In-shoe pressure data were collected at 50 Hz. Contact
      area, peak pressure, maximum force, and force-time integral were analyzed in
      eight different regions of the foot. Foot type was determined by examining
      navicular height, arch angle, rearfoot angle, and a clinical score. A series of 2
      x 2 repeated measures ANOVAs were used to determine statistical differences
      (alpha<0.05). A significant interaction existed between foot type and movement
      type for the maximum force in the medial midfoot. Total foot contact area,
      maximum force and peak pressure were significantly increased during running.
      Contact area in each insole area, except for the rearfoot, was significantly
      increased during running. Peak pressure and maximum force were significantly
      increased during running in each of the foot regions. However, the force-time
      integral was significantly decreased during running in the rearfoot, lateral
      midfoot, middle forefoot, and lateral forefoot. Significant differences between
      foot types existed for contact area in the medial midfoot and maximum force and
      peak pressure in the lateral forefoot. The maximum force and peak pressures were
      significantly decreased for the flat foot type. Therefore, individuals with a
      flat foot could be at a lower risk for lateral column metatarsal stress
      fractures, indicating that foot type should be assessed when determining an
      individual's risk for metatarsal stress fractures.

PMID- 18337104
TI  - Syntheses of 4,6'-epoxymorphinan derivatives and their pharmacologies.
AB  - A modification of the message site in the skeleton of naltrexone was carried out
      to improve the potency and selectivity of the compound for an opioid receptor
      subtype. In the course of conversion, we synthesized 7-membered ring ether
      derivatives, which had an inserted OCH(2) group between 4- and 6-positions of
      morphinan skeleton. One of the 7-membered ring ether derivatives possessed more
      potent antagonistic activity than naltrexone for the mu opioid receptor. Another
      compound possessing 17-methyl group derived from noroxycodone may be a mu opioid
      receptor partial agonist and showed analgesic activity. We are currently
      examining the subtype selectivity of these compounds.

PMID- 18337105
TI  - Sidechain-linked inhibitors of HIV-1 protease dimerization.
AB  - There is a great need for alternative modes of inhibition for the design of anti
      HIV therapies, due to the increased resistance of HIV to currently approved
      drugs. A novel strategy for generating potent dimerization inhibitors of HIV-1
      protease is described based on sidechain-linked interfacial peptides. In a number
      of cases the activity of these agents against HIV-1 protease was found to be
      among the most potent reported, with inhibitory constants in the low nM range.

PMID- 18337106
TI  - Synthesis of caged 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)-ones:
      Evaluating the minimum structure for apoptosis induction by gambogic acid.
AB  - We have reported the discovery of gambogic acid (GA) as a potent apoptosis
      inducer and the identification of transferrin receptor as its molecular target.
      In order to understand the basic pharmacophore of GA for inducing apoptosis and
      to discover novel and simplified derivatives as potential anti-cancer agents, we
      explored the synthesis of caged 2,3,3a,7a-tetrahydro-3,6-methanobenzofuran-7(6H)
      ones (4-oxatricyclo[4.3.1.0]decan-2-ones). Three types of 2,3,3a,7a-tetrahydro
      3,6-methanobenzofuran-7(6H)-ones based on xanthone, 2-phenylchromene-4-one and
      benzophenone, were synthesized using a Claisen/Diels-Alder reaction cascade. All
      the reactions produced the targeted caged compound as well as its neo-isomer. The
      caged compounds based on xanthone and 2-phenylchromene-4-one were found to
      maintain the apoptosis inducing and cell growth inhibiting activity of GA,
      although with less potency. The caged compounds based on benzophenone were found
      to be inactive. Our study determined the minimum structure of GA for its
      apoptosis inducing activity, which could lead to the development of simple
      derivatives as potential anti-cancer drugs.

PMID- 18337107
TI  - Synthesis and antioxidant properties of novel N-methyl-1,3,4-thiadiazol-2-amine
      and 4-methyl-2H-1,2,4-triazole-3(4H)-thione derivatives of benzimidazole class.
AB  - Some novel 1-methyl-4-(2-(2-substitutedphenyl-1H-benzimidazol-1
      yl)acetyl)thiosemicarbazides (16a-20a), 5-[(2-(substitutedphenyl)-1H-benzimidazol
      1-yl)methyl]-N-methyl-1,3,4-thiadiazol-2-amines (17b-20b), and 5-[(2
      (substitutedphenyl)-1H-benzimidazol-1-yl)methyl-4-methyl-2H-1,2,4-triazole-3(4H)
      thiones (16c-20c) were synthesized and tested for antioxidant properties by using
      various in vitro systems. Compounds 16a-20a were found to be a good scavenger of
      DPPH radical (IC(50), 26 microM; IC(50), 30 microM; IC(50), 43 microM; IC(50), 55
      microM; IC(50), 74 microM, respectively) when compared to BHT (IC(50), 54
      microM). Noteworthy results could not be found on superoxide radical. Compound
      19b, which is the most active derivative inhibited slightly lipid peroxidation
      (28%) at 10(-3)M concentration. Compound 17c inhibited the microsomal
      ethoxyresorufin O-deethylase (EROD) activity with an IC(50)=4.5 x 10(-4)M which
      is similarly better than the specific inhibitor caffeine IC(50)=5.2 x 10(-4)M.

PMID- 18337108
TI  - Image formation in structured illumination wide-field fluorescence microscopy.
AB  - We present a theoretical analysis of the image formation in structured
      illumination wide-field fluorescence microscopy (SIWFFM). We show that the
      optically sectioned images obtained with this approach possess the optical
      sectioning strengths comparable to those obtained with the confocal microscope.
      We further show that the transfer function behaviour is directly comparable to
      that of the true confocal instrument. The theoretical considerations are compared
      with and confirmed by experimental results.

PMID- 18337109
TI  - Surface and inner cell behaviour along skeletal muscle cell in vitro
      differentiation.
AB  - During muscle tissue differentiation, in particular in the formation of myotubes
      from the myoblasts, plasma membrane changes its morpho-functional
      characteristics. In this study, muscle cell membrane behaviour has been studied
      along the differentiation of C2C12, a mouse myoblastic adherent cell line. Flat
      undifferentiated cells, cultured for 3-4 days in the differentiation medium,
      progressively become thick, long and multinucleated myotubes covered with
      microvilli. They lose stress fibers and adhesion to the underlying substrate
      evidentiating an actin redistribution, followed by the spatial organization of
      thick and thin myofilaments. Sarcomeres and myofibrils occasionally appear, even
      if a certain percentage of "myosacs" containing randomly oriented filaments can
      be identified all along the differentiation. M-cadherin, a molecule involved in
      cell-cell adhesion, also appears in the early differentiation stage, during
      myoblast fusion. Occasional focal contractions can also be observed in myotubes,
      which prompt an electrophysiological membrane analysis. When studied by means of
      patch clamp technique, resting membrane potential appears to undergo a transient
      depolarization, while input resistance increases until day 5 after
      differentiation induction, then successively decreases. Capacitance declines
      until day 5, later appearing enhanced. Moreover, with the induction of
      differentiation, the pattern of functional voltage-dependent ion channels
      changes. Therefore, during myogenesis, cell maturation is coupled with changes in
      cell membrane morphological features and functional characteristics.

PMID- 18337110
TI  - Advances in the ultrastructural study of the implant-bone interface by
      backscattered electron imaging.
AB  - The biocompatibility of titanium implants in bone depends on the response shown
      by cells in contact with the implant surface. Several developments have been
      targeted at achieving successful implant treatment. The aim of this study was to
      develop a novel preparation procedure to evaluate the bone cell response produced
      at the bone-implant interface using the technique scanning electron microscopy
      with backscattered electron imaging (SEM-BSE). Dental prostheses with an SLA
      modified or TOP-modified surface were implanted in a toothless part of the
      mandibula in female pigs. The animals were sacrificed 12 weeks after surgery, at
      which time block specimens containing the implants were obtained. These specimens
      were then processed for SEM-BSE by optimizing a protocol involving chemical
      fixation and heavy metal staining. In addition, element distribution maps for the
      implant-bone tissue interface were obtained using a microanalytical system based
      on energy-dispersive X-ray spectrometry (EDS). This novel visualisation approach
      enabled a comprehensive study of the extracellular matrix and cell components of
      the host tissues neoformed around the implant. SEM-BSE images also provided
      ultrastructural details of the bone cells. This technique appears to be an
      effective and very promising tool for detailed studies on the implant-bone tissue
      interface and the host response to the bone incorporation process.

PMID- 18337111
TI  - Action of nitric oxide on healthy and inflamed human dental pulp tissue.
AB  - Irreversible pulpitis has been associated with pain and an increase in the number
      of pulp inflammatory cells. Based on the action of nitric oxide (NO) elsewhere,
      NO may possibly participate in the sensory and autonomic innervation of the
      dental pulp, and may influence local inflammatory responses. The purpose of this
      study was to analyze normal and inflamed human dental pulp for the presence of
      NADPH-diaphorase (NADPH-d), as an index of NO system activity. Six non-carious
      second premolar pulp tissue samples were obtained from young patients who
      required extractions for orthodontic reasons and six inflamed samples were
      obtained from symptomatic carious second premolars clinically diagnosed with
      irreversible pulpitis. Pulp tissue was carefully removed, fixed by immersion in a
      cold 4% PFA buffered solution for 120 min, rinsed in cold phosphate buffer, and
      quickly-frozen for cryostat sectioning. Pulp tissue was sectioned perpendicularly
      to the vertical axis of the tooth at 20 microm and processed for histochemistry.
      Sections of each specimen were stained with hematoxylin-eosin and other sections
      were subjected to histochemical NADPH-d detection. Results indicated the presence
      of NADPH reactivity within the pulps of both normal and carious teeth. In the
      normal teeth NADPH-d activity was detected in a small number of vascular
      endothelial cells and fibroblasts. The inflammatory response of the pulp from
      carious premolars was detected in connective tissue by the presence of an
      increased number of fibroblasts, angioblasts and collagen fibers. It was possible
      to determine the extent of odontoblast reactivity since the odontoblast layer was
      usually absent in these split-peel preparations. There were no obvious signs of
      stained pulpal nerve fibers. Overall NADPH-d staining was significantly more
      intense within inflamed pulp tissues compared to normal healthy samples (Mann
      Whitney test, p<0.002). These results suggest that NADPH-d may be used as a
      marker of inflammatory activity in pulpitis and provide the basis for further
      studies aiming to clarify the possible functions of NO in human dental pulp in
      pathophysiological situations.

PMID- 18337112
TI  - Microstructural investigation of nickel silicide thin films and the silicide
      silicon interface using transmission electron microscopy.
AB  - This article discusses the results of transmission electron microscopy (TEM)
      based investigation of nickel silicide (NiSi) thin films grown on silicon. Nickel
      silicide is currently used as the CMOS technology standard for local
      interconnects and in electrical contacts. Films were characterized with a range
      of TEM-based techniques along with glancing angle X-ray diffraction. The nickel
      silicide thin films were formed by vacuum annealing thin films of nickel (50 nm)
      deposited on (100) silicon. The cross-sectional samples indicated a final
      silicide thickness of about 110 nm. This investigation studied and reports on
      three aspects of the thermally formed thin films: the uniformity in composition
      of the film using jump ratio maps; the nature of the interface using high
      resolution imaging; and the crystalline orientation of the thin films using
      selected-area electron diffraction (SAED). The analysis highlighted uniform
      composition in the thin films, which was also substantiated by spectroscopy
      techniques; an interface exhibiting the desired abrupt transition from silicide
      to silicon; and desired and preferential crystalline orientation corresponding to
      stoichiometric NiSi, supported by glancing angle X-ray diffraction results.

PMID- 18337113
TI  - Protective effect of Castanea sativa and Quercus robur leaf extracts against
      oxygen and nitrogen reactive species.
AB  - Topical natural antioxidants are a useful strategy for the prevention of
      photoaging and oxidative stress mediated skin diseases. In view of this
      underlying principle, the screening of natural plant extracts with scavenging
      activity for pro-oxidant reactive species is a primary requirement for the
      development of new topical antioxidant formulations. In the present study, an
      ethanol:water (7:3) extract from Castanea sativa leaves and a ethanol:water (2:3)
      extract from Quercus robur leaves were evaluated for their putative in vitro
      scavenging effects on reactive oxygen species (ROS) namely superoxide radical
      (O(2)(-)), hydroxyl radical (HO()), peroxyl radical (ROO()), hydrogen peroxide
      (H(2)O(2)) and singlet oxygen ((1)O(2)) as well as on reactive nitrogen species
      (RNS) namely nitric oxide (()NO) and peroxynitrite (ONOO(-)). The extracts
      presented a high potency to scavenge the tested reactive species, all the IC(50)s
      being found at the microg/mL level. IC(50)s (mean+/-SE) for the ROS O(2)(
      ),HO(),H(2)O(2) and (1)O(2) were 13.6+/-1.8; 216+/-4; 410+/-8; 12.3+/-0.7
      microug/mL, respectively, for C. sativa, and 11.0+/-0.5; 285+/-22; 251+/-32;
      7.90+/-0.56 microg/mL, respectively, for Q. robur. The ORAC values obtained for
      ROO() were 1.24+/-0.13 for C. sativa and 1.09+/-0.06 for Q. robur. The IC(50)s
      (mean+/-SE) for ()NO and ONOO(-) were 3.10+/-0.14 and 1.49+/-0.10 microg/mL,
      respectively, for C. sativa and 3.13+/-0.11 and 0.95+/-0.02 microg/mL,
      respectively, for Q. robur. The content of total phenolics for C. sativa and Q.
      robur were 284+/-9 and 346+/-4 mg of gallic acid equivalents (GAE)/g of
      lyophilized extract respectively. The observed effects might be of relevance
      considering the putative interest of these extracts as topical antioxidants.

PMID- 18337114
TI  - Clinical implications of BRAF mutation in thyroid carcinoma.
AB  - Significant progress has recently been made in the clinical management of
      papillary thyroid carcinoma. The accuracy of diagnosis and prognostic
      stratification of this type of carcinoma are high but still fall below 100%. Lack
      of effective treatments for advanced stage papillary thyroid carcinoma leads to
      death in some patients. Approximately half of all such carcinomas harbor
      mutations in the gene encoding the serine/threonine-kinase B-type Raf kinase
      (BRAF), resulting in constitutive activation of the mitogen-activated protein
      kinase-extracellular-signal-regulated kinases signal transduction pathway. There
      is intriguing evidence that BRAF mutation testing of papillary thyroid carcinoma
      might improve the diagnosis, prognostic stratification and treatment of these
      tumors but large, prospective trials are needed to define the actual clinical
      impact of these approaches.

PMID- 18337115
TI  - Urocortins: emerging metabolic and energy homeostasis perspectives.
AB  - The effects of stress on energy balance and the involvement of the neuropeptide
      corticotropin releasing factor in modulating the anorexia of stress and
      sympathetic nervous system tone are well recognized. Currently, studies centered
      on the roles of the more recently described members of this family of ligands,
      the urocortins, and their preferred receptor, the corticotropin releasing factor
      type 2 receptor, suggest that they are important modulators of centrally
      controlled metabolic functions. In addition, urocortins also regulate fuel
      utilization in the periphery by acting locally within key metabolic tissues
      through autocrine and/or paracrine mechanisms. Recent findings have demonstrated
      that urocortin 2 and urocortin 3, by acting through their specific receptor in
      peripheral tissues, are novel modulators of glucose homeostasis and metabolic
      functions.

PMID- 18337116
TI  - Control of lipolysis by natriuretic peptides and cyclic GMP.
AB  - Human fat cell lipolysis was, until recently, thought to be mediated exclusively
      by a cAMP-dependent protein kinase (PKA)-regulated pathway under the control of
      catecholamines and insulin. We have shown that atrial- and B-type natriuretic
      peptides (ANP and BNP respectively) stimulate lipolysis in human fat cells
      through a cGMP-dependent protein kinase (PKG) signaling pathway independent of
      cAMP production and PKA activity. Pharmacological or physiological (exercise)
      increases in plasma ANP levels stimulate lipid mobilization in humans. This
      pathway becomes important during chronic treatment with beta-adrenoceptor
      antagonists, which inhibit catecholamine-induced lipolysis but enhance cardiac
      ANP release. These findings have metabolic implications and point to potential
      problems when natriuretic peptide secretion is altered or during therapeutic use
      of recombinant BNP.

PMID- 18337117
TI  - Evaluation of the transforming growth factor beta1 codon 25 (Arg-->Pro)
      polymorphism in alcoholic liver disease.
AB  - INTRODUCTION: Liver cirrhosis develops only in a minority of heavy drinkers.
      Genetic factors may account for some variation in the progression of fibrosis in
      alcoholic liver disease (ALD). Transforming growth factor beta 1 (TGFbeta1) is a
      key profibrogenic cytokine in fibrosis and its gene contains several polymorphic
      sites. A single nucleotide polymorphism at codon 25 has been suggested to affect
      fibrosis progression in patients with chronic hepatitis C virus infection, fatty
      liver disease, and hereditary hemochromatosis. Its contribution to the
      progression of ALD has not been investigated sufficiently so far. PATIENTS AND
      METHODS: One-hundred-and-fifty-one heavy drinkers without apparent ALD, 149
      individuals with alcoholic cirrhosis, and 220 alcoholic cirrhotics who underwent
      liver transplantation (LTX) were genotyped for TGFbeta1 codon 25 variants.
      RESULTS: Univariate analysis suggested that genotypes Arg/Pro or Pro/Pro are
      associated with decompensated liver cirrhosis requiring LTX. However, after
      adjusting for patients' age these genotypes did not confer a significant risk for
      cirrhosis requiring LTX. CONCLUSION: TGFbeta1 codon 25 genotypes Arg/Pro or
      Pro/Pro are not associated with alcoholic liver cirrhosis. Our study emphasizes
      the need for adequate statistical methods and accurate study design when
      evaluating the contribution of genetic variants to the course of chronic liver
      diseases.

PMID- 18337118
TI  - ABC transporters and the accumulation of imatinib and its active metabolite
      CGP74588 in rat C6 glioma cells.
AB  - Imatinib (Glivec, Gleevec, STI571) is a small tyrosine kinase inhibitor that is
      currently in phase II clinical trials in patients with recurrent glioblastoma.
      Its therapeutic benefit is minimal, although it is greater in some patients when
      combined with hydroxyurea. Imatinib is transported by human and rodent ATP
      binding cassette (ABC) transporters like P-glycoprotein (Pgp) and the breast
      cancer resistance protein (BCRP). We have investigated whether ABC transporters
      determine the pharmacokinetics of imatinib and its pharmacological active
      metabolite CGP74588 in rat C6 glioma cells. ABC transporter expressions were
      measured by quantitative reverse transcriptase-polymerase chain reaction (qRT
      PCR). C6 cells express high concentrations of the Pgp-encoding gene Mdr1b and a
      10-fold smaller amount of the Pgp-encoding gene Mdr1a. The relative expression of
      ABC transporter genes are: Mdr1b>Mrp4>Mrp1>Mrp5>Mdr1a>Mrp3>Mrp2>Bcrp. The
      accumulation of imatinib into C6 cells increased linearly with the extracellular
      concentration of imatinib (0.5-50microM) and was not increased by zosuquidar
      (selective Pgp inhibitor) or elacridar (inhibitor of both Pgp and Bcrp). In
      contrast, there was less CGP74588 than imatinib in C6 cells and its concentration
      increased with the extracellular concentration in a sigmoid fashion. Lastly,
      10microM valspodar (selective Pgp inhibitor), elacridar and zosuquidar all
      increased the accumulation of CGP74588 by 2.5-fold. Thus CGP74588 is readily
      transported by the Pgp in rat C6 gliomas cells, which raises the question of the
      role of Pgp in the resistance of recurrent glioblastomas to imatinib.

PMID- 18337119
TI  - Investigations of prion and virus safety of a new liquid IVIG product.
AB  - A highly purified, liquid, 10% immunoglobulin product stabilized with proline,
      referred to as IgPro10 has recently been developed. IgG was purified from human
      plasma by cold ethanol fractionation, octanoic acid precipitation and anion
      exchange chromatography. The manufacturing process includes two distinctly
      different partitioning steps and virus filtration, which were also assessed for
      the removal of prions. Prion removal studies used different spike preparations
      (brain homogenate, microsomes, purified PrP(sc)) and three different detection
      methods (bioassay, Western blot, conformation-dependent immunoassay). All of the
      investigated production steps were shown to reduce significantly all different
      spike preparations, resulting in an overall reduction of >10log(10). Moreover,
      the biochemical assays proved equally effective to the bioassay for the
      demonstration of prion elimination. Four of the manufacturing steps cover three
      different mechanisms of virus clearance. These are: i) virus inactivation; ii)
      virus filtration; and iii) partitioning. These mechanisms were assessed for their
      virus reduction capacity. Virus validation studies demonstrated overall reduction
      factors of >18log(10) for enveloped and >7log(10) for non-enveloped model
      viruses. In conclusion, the IgPro10 manufacturing process has a very high
      reduction potential for prions and for a wide variety of viruses resulting in a
      state-of-the-art product concerning safety towards known and emerging pathogens.

PMID- 18337120
TI  - Intra-cellular storage, transport and exocytosis of halogenated compounds in
      marine red alga Laurencia obtusa.
AB  - The production of secondary metabolites in seaweed have been related to a
      capability to partition compounds into cellular specialized storage structures,
      like gland cells and the corps en cerise (CC) or cherry bodies. The possible
      mechanisms that bring these compounds to the thallus surface remain poorly
      understood. Therefore, the aim of this work is perform a characterization of the
      CC and determine the intra-cellular dynamics of halogenated compounds in
      Laurencia obtusa. The dynamics of CC and the mechanisms related to the intra
      cellular transport of halogenated compounds were evaluated by using optical
      tweezers and time-lapse video microscopy. The CC were isolated and its elemental
      composition was characterized using X-ray microanalysis. The cellular
      distribution of halogenated compounds was also demonstrated by fluorescence
      microscopy. Three-dimensional reconstruction technique was used to provide a
      visualization of the structures that connect CC to cell periphery. As main
      findings, we confirmed that the halogenated compounds are mainly found in CC and
      also in vesicles distributed along the cytoplasm and within the chloroplasts. We
      demonstrated that CC is mechanically fixed to cell periphery by a stalk-like
      connection. A vesicle transport though membranous tubular connections was seen
      occurring from CC to cell wall region. We also demonstrated a process of cortical
      cell death event, resulting in degradation of CC. We suggested that the vesicle
      transportation along membranous tubular connections and cell death events are
      related to the mechanisms of halogenated compounds exudation to the thallus
      surface and consequently with defensive role against herbivores and fouling.

PMID- 18337121
TI  - Induction of interferon system genes in Atlantic salmon by the imidazoquinoline S
      27609, a ligand for Toll-like receptor 7.
AB  - Imidazoquinolines represented by imiquimod and its derivative S-27609, have
      previously been shown to have potent antiviral and antitumor activity in several
      mammalian models. Much of the antiviral properties of imidazoquinolines have been
      ascribed to induction of IFN-alpha in peripheral blood mononuclear cells most
      notably plasmacytoid dendritic cells. Toll-like receptor (TLR) 7 has been
      identified as the receptor for imiquimod and S-27609 in mammals. In this work we
      show that S-27609 induces expression of IFN-alpha1/alpha2, Mx, ISG15 and IFN
      gamma in organs of Atlantic salmon, which suggests that salmon responds to S
      27609 through a TLR7-like receptor. The kinetics of gene expression in liver and
      head kidney induced by S-27609 was compared with that induced by the double
      stranded RNA poly I:C, which is a ligand for TLR3 and the RNA helicase MDA5. In
      liver, S-27609 and poly I:C both induced transcripts for IFN-alpha1/alpha2, Mx
      and ISG15 with a peak at about 24h. In head kidney, poly I:C induced IFN
      alpha1/alpha2 and Mx with one peak at about 24h. In contrast, S-27609 induced a
      biphasic increase of IFN-alpha1/alpha2 and Mx transcripts in head kidney with a
      minor peak at 14-24h and another increase starting at 72h. The other major
      difference in gene induction by the two stimulants was that S-27609 induced much
      lower levels of IFN-alpha1/alpha2 than poly I:C during the early time stages (14
      48h) both in liver and head kidney. The difference in induction of IFN
      alpha1/alpha2 by S-27609 and poly I:C may be a consequence of different cell
      targets for the two stimulants where S-27609 primarily induces IFNs through
      immune cells whereas poly I:C induces IFNs in most nucleated cells.

PMID- 18337122
TI  - Effects of inulin on gilthead seabream (Sparus aurata L.) innate immune
      parameters.
AB  - Inulin, a fructooligossacharide, is a prebiotic that plays an important role in
      the immune function in mammals, but it has never been assayed in other vertebrate
      groups. Thus, we have studied the inulin effects on the gilthead seabream (Sparus
      aurata L.) innate immune response both in vitro and in vivo. For the in vitro
      study, head-kidney leucocytes were incubated with inulin (ranging from 0 to 1000
      microg ml(-1)) for 30, 90, 180 and 300 min and 24h and any effect was observed on
      leucocyte viability or the main innate cellular immune responses (leucocyte
      peroxidase, phagocytic, respiratory burst and natural cytotoxic activities). For
      the in vivo study, seabream specimens were fed for 1 or 2 weeks with a commercial
      diet supplemented with inulin: 0 (control), 5 or 10 g inulin kg(-1) diet (0.5 and
      1%, respectively). Inulin produced a significant inhibition in phagocytosis and
      respiratory burst in leucocytes from specimens fed diets containing 0.5% or 1% of
      inulin for 1 week. Based on the present results, inulin does not seem to be a
      good immunostimulant for seabream, though its effects in other species and
      combined with other immunostimulans (i.e. probiotics) might be of great interest.

PMID- 18337123
TI  - Molecular cloning of liver angiotensinogen gene in ayu (Plecoglossus altivelis)
      and mRNA expression changes upon Aeromonas hydrophila infection.
AB  - Angiotensinogen (AGT) is thought to be an acute phase protein, because in mammals
      its plasma concentrations increase during inflammation induced by
      lipopolysaccharides (LPS). A full-length cDNA clone of the AGT gene, 1828bp in
      size, was isolated from the fish ayu (Plecoglossus altivelis). Its deduced amino
      acid sequence of 462 residues had 57.7-68.6%, 30.2% and 23.3-27.4% identity to
      those sequenced from other fish, chicken and mammals, respectively. Ayu-AGT is
      most closely related to that of silver sea bream and the phylogenetic tree
      largely reflects the currently accepted animal relationships. In healthy control
      fish, AGT transcripts were found to be present in a number of tissues including
      brain, spleen, liver, kidney and intestine. The amplification was found to be the
      highest in the liver. In Aeromonas hydrophila-infected ayu, AGT transcripts
      significantly increased in various tissues, suggesting a possible relationship
      between AGT mRNA expression and the vascular inflammation caused by bacterial
      infection. AGT transcripts could be detected in the heart and gill of bacteria
      infected ayu that were not detected in control fish, but still not in the muscle.
      This is the first report of changes in fish AGT transcripts upon bacterial
      infection.

PMID- 18337124
TI  - Neocortical reorganization in spina bifida.
AB  - Normal brain development throughout childhood and adolescence is usually
      characterized by decreased cortical thickness in the frontal regions as well as
      region-specific patterns of increased white matter myelination and volume. We
      investigated total cerebral volumes, neocortical surface area, and neocortical
      thickness in 16 children with a neural tube defect, spina bifida myelomeningocele
      (SB), and 16 age-matched typically developing controls using a semi-automated,
      quantitative approach to MRI-based brain morphometry. The results revealed no
      significant group differences in total cerebral volume. However, group
      differences were observed in the global distribution of distinct tissue classes
      within the cerebrum: the SB group demonstrated a significant 15% reduction in
      total white matter and a 69% increase in cerebrospinal fluid, with no differences
      in total gray matter. Group comparisons of neocortical surface area assessments
      were significantly smaller in the occipital regions for SB, with no significant
      group differences in the frontal regions. Group comparisons of cortical thickness
      measurements demonstrated reduced cortical thickness in all regions except the
      frontal regions, where the SB group exhibited an increase relative to the PC
      group. Although regional patterns of thinning may be associated with the
      mechanical effects of hydrocephalus, the overall reduction in white matter and
      increased neocortical thickness in the frontal regions suggest that SB reflects a
      long-term disruption of brain development that extends far beyond the neural tube
      defect in the first weeks of gestation.

PMID- 18337125
TI  - Spatiotemporal frequency tuning of BOLD and gamma band MEG responses compared in
      primary visual cortex.
AB  - In this study, the spatial and temporal frequency tuning characteristics of the
      MEG gamma (40-60 Hz) rhythm and the BOLD response in primary visual cortex were
      measured and compared. In an identical MEG/fMRI paradigm, 10 participants viewed
      reversing square wave gratings at 2 spatial frequencies [0.5 and 3 cycles per
      degree (cpd)] reversing at 5 temporal frequencies (0, 1 6, 10, 15 Hz). Three
      dimensional images of MEG source power were generated with synthetic aperture
      magnetometry (SAM) and showed a high degree of spatial correspondence with BOLD
      responses in primary visual cortex with a mean spatial separation of 6.5 mm, but
      the two modalities showed different tuning characteristics. The gamma rhythm
      showed a clear increase in induced power for the high spatial frequency stimulus
      while BOLD showed no difference in activity for the two spatial frequencies used.
      Both imaging modalities showed a general increase of activity with temporal
      frequency, however, BOLD plateaued around 6-10 Hz while the MEG generally
      increased with a dip exhibited at 6 Hz. These results demonstrate that the two
      modalities may show activation in similar spatial locations but that the
      functional pattern of these activations may differ in a complex manner,
      suggesting that they may be tuned to different aspects of neuronal activity.

PMID- 18337126
TI  - Dusky salamanders (Desmognathus, Plethodontidae) from the Coastal Plain: multiple
      independent lineages and their bearing on the molecular phylogeny of the genus.
AB  - Recent phylogenetic reassessment of the lungless salamanders (Plethodontidae)
      confirmed a major life-history reversal-from direct development to an aquatic
      larval stage-in the dusky salamanders (Desmognathus) of eastern North America.
      This reversal initiated high rates of lineage accumulation, reputedly generating
      the species richness and ecological breath that now characterize Desmognathus.
      Certain important aspects of the radiation, e.g., ecomorphological evolution,
      have been identified through intense sampling effort of Appalachian Highland
      lineages. However, the research preoccupation on montane species has left
      overlooked a significant component of dusky salamander distribution-the Coastal
      Plain. We present the first molecular phylogeny for Desmognathus to incorporate
      extensive coverage from the Atlantic and Gulf coastal plains. We examined 38
      Coastal Plain populations in conjunction with 45 additional populations,
      representing 16 of the 19 nominal species. Bayesian analysis of 88 mitochondrial
      cox1 haplotypes diagnosed eight independent population lineages within the
      Coastal Plain, a number at odds with the region's three currently recognized
      species. Desmognathus has apparently experienced a complex biogeographic history
      in this physiographic region, one involving multiple invasions and several
      ecological transitions from lotic to lentic habitats.

PMID- 18337127
TI  - Validation of a larval zebrafish locomotor assay for assessing the seizure
      liability of early-stage development drugs.
AB  - INTRODUCTION: Seizure liability is an adverse property of new candidate drugs
      typically detected only in later stage pre-clinical safety studies. Consequently,
      pharmaceutical discovery needs small scale (microplate-based), rapid throughput
      screens to 'front-load' such adverse endpoints in order to reduce associated
      attrition rates. Of the potential methods available, previously published studies
      have shown that the quantification of seizure-associated locomotion in the larval
      zebrafish (Danio rerio) offers high potential for development into such a screen.
      Here, we present methodology and validation data (on 25 compounds) from a larval
      zebrafish (Zf) convulsant assay, based on the quantification of high speed
      locomotion after exposure to a range of test compounds. METHODS: All assays were
      undertaken in 7 days post fertilization (dpf), WIK-strain Zf larvae, at 27+/-1
      degrees C. The blinded validation test set consisted of 17 positive and 8
      negative controls, based on literature evidence for seizure liability. Initially,
      a Maximum Tolerated Concentration (MTC) assay was undertaken on each compound to
      identify the maximum concentration not causing general toxicity, sedation or
      overt neuromuscular effects. Next, the convulsant assay was undertaken on 5
      concentrations from the MTC down, plus a dilution water control. Exposed larvae
      were videotracked for 1 h, using the Viewpoint Videotrack for Zebrafish system,
      and high speed movements, typically associated with seizure-like locomotor
      activity, were quantified. RESULTS: According to classification criteria proposed
      by the European Centre for the Validation of Alternative Methods (ECVAM), the
      data generated appeared to offer "sufficient" predictivity (72% overall),
      particularly considering the potential for throughput and likely positioning
      within a safety pharmacology front-loading screening cascade. DISCUSSION:
      Possible reasons for the misclassifications are discussed, and potential
      improvements to increase sensitivity and specificity outlined. In all, these
      initial validation data suggest that this assay offers potential as a medium
      throughput screen aimed at the early drug discovery detection of this complex
      safety pharmacological endpoint.

PMID- 18337128
TI  - (1)H-MRS profile in MRI positive- versus MRI negative patients with temporal lobe
      epilepsy.
AB  - INTRODUCTION: The objective of this study was to quantitate and compare
      ipsilateral total N-acetyl aspartate (tNAA), creatine (Cr), choline (Cho), myo
      inositol (m-Ins) and glutamate plus glutamine (Glx) levels in the hippocampi of
      patients with temporal lobe epilepsy (TLE) with and without magnetic resonance
      imaging (MRI) evidence for mesial temporal sclerosis (MRI positive/negative).
      PATIENTS AND METHODS: Twenty-three age matched healthy controls and 26
      consecutive patients with unilateral TLE, based on intensive 24h video-EEG, were
      investigated with proton magnetic resonance spectroscopy ((1)H-MRS) (17 with
      unilateral hippocampal sclerosis (HS) in MRI-MRI positive; 9 MRI negative). For
      statistical analysis one-way analysis of variance (ANOVA) with post hoc multiple
      comparisons and Bonferroni correction was applied. The significance level was
      based on p<0.05. RESULTS: The mean tNAA level ipsilateral to the seizure focus
      was significantly decreased in MRI negative, respectively MRI positive patients
      in comparison to healthy controls (p<0.001). The lowest tNAA level was noticed in
      the MRI positive group (p<0.001). Statistical analysis highlighted a clear "tNAA
      cut-off" (95% confidence interval) between MRI positive- and MRI negative
      patients and healthy controls. Mean level of Glx and m-Ins was not significantly
      elevated or reduced. However, in individual cases a significant elevation was
      noticed for Glx in MRI negative patients, respectively for m-Ins in MRI positive
      patients. CONCLUSION: MRI negative TLE patients have a different MRS profile than
      MRI positive patients (HS) with marginal but significant decrease of tNAA. Our
      results reveal a clear "tNAA cut-off" between the groups. The value of m-Ins and
      Glx in focus detection in TLE patients remains controversy.

PMID- 18337129
TI  - The feasibility of characterizing the spatial distribution of cartilage T(2)
      using texture analysis.
AB  - OBJECTIVE: The purpose of this study was (1) to characterize the spatial
      distribution of cartilage T(2) in postmenopausal osteoarthritis (OA) patients and
      age-matched healthy subjects using second order texture measures at baseline, and
      (2) to analyze changes in the texture of cartilage T(2) after 9 months. METHODS:
      3.0T-MRI of the knee was performed in 8 mild OA patients and 10 age-matched
      controls at baseline and after 9 months. Cartilage T(2), volume, and average
      thickness were calculated in all patients. Texture analysis, based on the gray
      level co-occurrence matrix, was performed on the cartilage T(2) maps. Texture
      parameters, including entropy and angular second moment, were calculated at 0
      degrees (corresponding to the anterior-posterior axis) and at 90 degrees
      (corresponding to the superior-inferior axis), with pixel offsets ranging from 1
      to 3 pixels. RESULTS: Least square means analysis showed that mean T(2) values,
      their standard deviation (SD), and their entropy were greater (P<0.05) in OA
      patients than in controls. Over 9 months, the SD and entropy of cartilage T(2)
      significantly (P<0.05) decreased in OA patients, while no significant changes
      were evident in cartilage thickness or volume. CONCLUSION: The mean cartilage
      T(2) values, their SD, and their entropy were greater in OA patients than in
      controls, indicating that the T(2) values in osteoarthritic cartilage are not
      only elevated, but also more heterogeneous than those in healthy cartilage. The
      longitudinal results demonstrate that changes in texture parameters of cartilage
      T(2) may precede morphological changes in thickness and volume in the progression
      of OA.

PMID- 18337130
TI  - Kinesin-driven transport in cell-free environment.
AB  - Conventional kinesin is an ATPase-active motor protein that is involved in the
      microtubule-dependent transport of cytoplasmic cargoes. The present paper
      provides a condensed overview on kinesin-1 and its motility generation outside a
      living cell. Moreover, it demonstrates that the neuron-specific kinesin KIF5A
      enables the formation of microtubules under conditions where pure tubulin does
      not assemble.

PMID- 18337131
TI  - Non-enzymatic fast repair of DNA oxidative damage might also exist in cells.
AB  - Many studies have shown that in a chemical system natural polyphenols can rapidly
      repair DNA oxidative damage. In this paper we report that in a cellular system
      the non-enzymatic fast repair activities of two natural polyphenols might also
      exist. The viability of a Chinese hamster ovary cell line (AA8) highly expressing
      the XRCC1 gene (a DNA repairing protein) treated with H2O2 is significantly
      higher than that of a normal Chinese hamster ovary cell line (CHO). Following
      inhibition of the enzymatic repair system by different inhibitors--methoxyamine
      (MX), 3-aminobenzamide (3AB) or nicotinamide (NIC)--DNA oxidative damage by H2O2
      increased 2-5-fold in both cell lines. However, when natural polyphenols-
      rosmarinic acid (RA) or verbascoside (VER)--were added, DNA oxidative damage was
      significantly reduced. This decrease of DNA oxidative damage by RA or VER is not
      due to their scavenging activity for reactive oxygen species (ROS) because cells
      suffered from heavy ROS throughout the whole experimental process. Therefore, the
      decrease of DNA damage might be due to their non-enzymatic fast repair
      mechanisms. Further investigation showed that H2O2 induced a drop in the
      mitochondrial membrane potential (MMP), and that RA and VER were able to
      attenuate the drop. Previous studies have shown that H2O2 initiates a chain of
      events in cells, involving mtDNA damage, a drop in MMP and loss of repair
      activity. These results, taken together with our present results, suggest that
      the non-enzymatic fast repair mechanism exists not only in chemical systems but
      also might exist in cells.

PMID- 18337132
TI  - The peripheral chromosome scaffold, a novel structural component of mitotic
      chromosomes.
AB  - Using an original high-salt extraction protocol, we observed a novel chromosome
      substructure, referred to as the peripheral chromosome scaffold. This chromosome
      domain contained the perichromosomal layer proteins pKi-67, B23/nucleophosmin and
      fibrillarin, but no DNA fragments (i.e., the loop domain bases were not
      associated with the peripheral scaffold). Modern models of chromosome
      organization do not predict the existence of a peripheral chromosome scaffold
      domain, and thus our observations have conceptual implications for understanding
      chromosome architecture.

PMID- 18337133
TI  - Detection and characterisation of Shiga toxin-producing Escherichia coli other
      than Escherichia coli O157:H7 in wild ruminants.
AB  - Shiga toxin-producing Escherichia coli (STEC) are an important group of emerging
      pathogens, with ruminants recognised as their main natural reservoir. The aim of
      this work was to establish the prevalence of non-O157 STEC in free-ranging wild
      ruminants in the Extremadura region of Spain and to characterise them
      phenogenotypically. Faecal samples were collected from 243 wild ruminants,
      including Cervus elaphus, Capreolus capreolus, Dama dama and Ovis musimon and
      were examined for STEC using both phenotypic (Vero cells) and genotypic (PCR and
      PFGE) methods. Shiga toxin-producing Escherichia coli were isolated from 58
      (23.9%) of the samples and a total of 65 isolates were characterised. A PCR
      method indicated that 11 (16.9%) strains carried the stx(1) gene, 44 (67.7%)
      carried the stx(2) gene and 10 (15.4%) carried both these genes. The ehxA gene
      was detected in 37 (57%) of the isolates but none contained either the eae or saa
      genes. The isolates were from a total of 12 'O' serogroups, although 80% were
      restricted to the O2, O8, O128, O146, O166 and O174 serogroups. The most commonly
      isolated STEC bacteria, which were from the O146 serogroup, exhibited a high
      degree of polymorphism as indicated by PFGE. Shiga toxin-producing Escherichia
      coli isolates of serogroups O20, O25, O166, O171, O174 and O176 had not
      previously been found in wild ruminants. This is the first study to confirm that
      wild ruminants in Spain are a reservoir of STEC and are thus a potential source
      of human infection.

PMID- 18337134
TI  - Feature-preserving adaptive mesh generation for molecular shape modeling and
      simulation.
AB  - We describe a chain of algorithms for molecular surface and volumetric mesh
      generation. We take as inputs the centers and radii of all atoms of a molecule
      and the toolchain outputs both triangular and tetrahedral meshes that can be used
      for molecular shape modeling and simulation. Experiments on a number of molecules
      are demonstrated, showing that our methods possess several desirable properties:
      feature-preservation, local adaptivity, high quality, and smoothness (for surface
      meshes). We also demonstrate an example of molecular simulation using the finite
      element method and the meshes generated by our method. The approaches presented
      and their implementations are also applicable to other types of inputs such as 3D
      scalar volumes and triangular surface meshes with low quality, and hence can be
      used for generation/improvement of meshes in a broad range of applications.

PMID- 18337135
TI  - Application of the independent molecule model to elucidate the dynamics of
      structure I methane hydrate: a second report.
AB  - Two model systems of methane hydrate are constructed. One has a small cage
      surrounded by 12 large cages. The other has a large cage surrounded by four small
      cages and ten large cages. Three different H-bonding network patterns between
      waters are formed, and three random configurations of methane in each cage are
      chosen. A new method called the surface water fixed model is presented in which
      the energy minimum conformations for both model systems are preserved close to
      the X-ray crystallized structure. With normal mode analysis, we calculated
      frequencies of 2916.6 cm(-1) for a small cage at a centre, 2915.9 cm(-1) not at a
      centre, and 2911.7 cm(-1) for a large cage at a centre, and 2911.3 cm(-1) not at
      a centre. These frequencies are in moderate agreement with the corresponding
      Raman spectra, though not adequate. With our new method, however, it should be
      possible to improve agreement with the Raman spectra, if a model system vastly
      larger than the present model systems were constructed.

PMID- 18337136
TI  - Purification and antibacterial characterization of a novel isoform of the Manila
      clam lectin (MCL-4) from the plasma of the Manila clam, Ruditapes philippinarum.
AB  - In many bivalve molluscs, lectins are present in the hemolymph and are thought to
      be important for internal host defense mechanisms. For this study, we purified a
      novel isoform of the Manila clam lectin (designated MCL-4) from the plasma of the
      Manila clam, Ruditapes philippinarum, using affinity chromatography and gel
      filtration. Native PAGE results showed that the MCL-4 consisted of 70 kDa
      protein. MCL-4 was found to be composed of 58-kDa and 43-kDa bands when examined
      using SDS-PAGE under reducing and non-reducing conditions. The native MCL-4 was
      revealed as a 147 kDa molecular mass protein by gel filtration. The purified MCL
      4 agglutinates calcium-dependently in the erythrocytes of sheep and rabbit, but
      not in cells of the three species of marine bacteria tested. However, the
      phagocytic ability of the R. philippinarum hemocytes for the MCL-4-opsonized
      Vibrio tubiashii cells was significantly greater than that for the BSS-treated
      bacterial cells. Addition of purified MCL-4 markedly suppressed Alteromonas
      haloplanktis growth. These results suggest that MCL-4, because of its opsonizing
      and bacteriostatic properties, might contribute to the host defense mechanisms
      against invading microorganisms in R. philippinarum.

PMID- 18337137
TI  - Cardiomyopathy and carnitine deficiency.
AB  - Carnitine is essential for the transfer of long-chain fatty acids across the
      mitochondrial membrane for subsequent beta-oxidation. A defect in the high
      affinity carnitine transporter OCTN2 causes autosomal recessive primary carnitine
      deficiency that can present with hypoketotic hypoglycemia, mainly in infancy or
      cardiomyopathy. Heterozygotes for primary carnitine deficiency can have mildly
      reduced plasma carnitine levels and can develop benign cardiac hypertrophy. In
      animal models, heterozygotes for this disease have a higher incidence of
      cardiomyopathy with aging. This study tested whether heterozygosity for primary
      carnitine deficiency was associated with cardiomyopathy. The frequency of
      mutations in the SLC22A5 gene encoding the OCTN2 carnitine transporter was
      determined in 324 patients with cardiomyopathy and compared to that described in
      the normal population. Missense variations identified in normal controls and
      patients with cardiomyopathy were expressed in Chinese Hamster Ovary cells to
      confirm a functional effect. Exons 2-10 of the SLC22A5 gene were amplified by PCR
      in the presence of LCGreen I and analyzed by dye-binding/high-resolution thermal
      denaturation. Exon 1 of the gene was sequenced in all patients. Heterozygosity
      for a few variants (L144F, T264M, I312V, E317K, and R488H) was found in 6/324
      patients with cardiomyopathy. Expression of these variants in CHO cells indicated
      that T264M decreased, E317K increased, while L144F, I312V, and R488H did not
      significantly affect carnitine transport. Expression in CHO cells of all the
      variants identified in a normal population indicated that only two had a
      functional effect (L17F and Y449D), while L144F, V481I, V481F, M530V, and P549S
      did not change significantly carnitine transport. The frequency of variants
      affecting carnitine transport was 2/324 patients with cardiomyopathy (0.61%) not
      significantly different from frequency of 3/270 (1.11%) in the general
      population. These results indicate that heterozygosity for primary carnitine
      deficiency is not more frequent in patients with unselected types of
      cardiomyopathy and is unlikely to be an important cause of cardiomyopathy in
      humans.

PMID- 18337138
TI  - Hereditary and acquired diseases of acyl-coenzyme A metabolism.
AB  - Coenzyme A (CoA) sequestration, toxicity or redistribution (CASTOR) is predicted
      to occur in many hereditary and acquired conditions in which the degradation of
      organic acyl esters of CoA is impaired. The resulting accumulation of CoA esters
      and reduction of acetyl-CoA and free CoA (CoASH) will then trigger a cascade of
      reactions leading to clinical disease. Most conditions detected by expanded
      neonatal screening are CASTOR diseases. We review acyl-CoA metabolism, including
      CoASH synthesis, transesterification of acyl-CoAs to glycine, glutamate or l
      carnitine and hydrolysis of CoA esters. Because acyl-CoAs do not cross biological
      membranes, their main toxicity is intracellular, primarily within mitochondria.
      Treatment measures directed towards removal of circulating metabolites do not
      address this central problem of intracellular acyl-CoA accumulation. Treatments
      usually involve the restriction of dietary precursors and administration of
      agents like l-carnitine and glycine, which can accept the transfer of acyl groups
      from acyl-CoA, liberating CoASH. Many hereditary CASTOR patients are chronically
      ill, with persistent symptoms and continuously abnormal metabolites in blood and
      urine despite good compliance with treatment. Conversely, asymptomatic patients
      are also common in hereditary CASTOR conditions. Future challenges include the
      understanding of pathophysiologic mechanisms in CASTOR diseases, the discovery of
      reliable predictors of outcome in individual patients and the establishment of
      therapeutic trials with sufficient numbers of patients to permit solid
      therapeutic conclusions.

PMID- 18337139
TI  - Reactivation of Chagas disease with central nervous system involvement in HIV
      infected patients in Argentina, 1992-2007.
AB  - OBJECTIVES: The objective of this study was to evaluate clinical and
      microbiological characteristics of Chagas disease (ChD) with central nervous
      system (CNS) involvement in AIDS patients. METHODS: This was a retrospective
      study of clinical and laboratory findings of HIV-infected patients with a
      confirmed diagnosis of ChD involving the CNS during the period 1992-2007 at the
      "Francisco J. Muniz" Infectious Diseases Hospital, Buenos Aires, Argentina.
      RESULTS: Of a total of 15 patients, 14 were male and the median age was 33 years
      (range 25-54 years). Seven out of nine had lived in a Chagas endemic area and
      7/10 were intravenous drug users (IDUs). The disease was reactivated during
      corticosteroid therapy in three patients. Clinical manifestations were: headache
      (11/15), focal neurological deficits (9/15), fever (9/15), meningismus (7/15),
      seizures (7/15), altered mental status (5/15), and cardiac involvement (3/10).
      The median CD4 T-cell count at the time of reactivation was 64cells/microl (range
      1-240). Twelve of 14 had positive serology for Trypanosoma cruzi; the two
      negative were IDUs. Cerebrospinal fluid (CSF) findings (median (range)): cell
      count 5/mm(3) (2-90), protein level 0.68g/l (0.1-1.84), and glucose level 0.45g/l
      (0.13-0.73). CSF direct examination for T. cruzi was positive in 11/13.
      Neuroimaging findings showed a single hypodense lesion in 7/14 and normal images
      in 2/14. Twelve patients were treated with benznidazole. The global mortality was
      79% (11/14). CONCLUSIONS: ChD reactivation should be considered as a differential
      diagnosis of meningoencephalitis in HIV patients with low CD4 T-cell counts,
      previous residency in an endemic area, and/or IDUs. Whenever possible, lumbar
      puncture should be performed because of the high accuracy for early diagnosis.

PMID- 18337140
TI  - Risk factors for mortality in symptomatic hyperlactatemia among HIV-infected
      patients receiving antiretroviral therapy in a resource-limited setting.
AB  - OBJECTIVES: To determine the mortality rate and risk factors after experiencing
      symptomatic hyperlactatemia in HIV-infected patients receiving antiretroviral
      therapy (ART). METHODS: A retrospective cohort study was conducted among patients
      who were diagnosed with symptomatic hyperlactatemia (lactate >2.5mmol/l) between
      January 2004 and April 2006. All patients were followed until 3 months after the
      diagnosis. RESULTS: One hundred and twenty-five patients were included in the
      study. The mean+/-standard deviation (SD) age was 39.9+/-10.1 years and body
      weight was 58.2+/-16.9kg; 60.8% were male. Symptomatic hyperlactatemia in 114
      (91.2%) was associated with receiving d4T, in five (4.0%) with d4T+ddI, in four
      (3.2%) with ZDV+ddI, and in two (1.6%) with ddI (d4T, stavudine; ddI, didanosine;
      ZDV, zidovudine). The median duration of ART was 13 months. Nine (7.2%) patients
      died. Patients who died had a higher mean lactate level (8.0 vs. 5.1mmol/l) and
      mean alanine aminotransferase (ALT; 164 vs. 48U/l) at the time of diagnosis when
      compared to those who survived (p<0.05). Patients who died had a lower mean
      weight than those who survived (48 vs. 59kg, p=0.008). By logistic regression,
      mortality was associated with patients whose body weight was <45kg (p=0.014, odds
      ratio (OR) 9.090, 95% confidence interval (CI) 1.575-52.632) and whose serum
      lactate was >10mmol/l (p=0.004, OR 20.372, 95% CI 2.610-159.001). CONCLUSIONS:
      The mortality rate of symptomatic hyperlactatemia among HIV-infected patients
      receiving ART is substantial. Almost all patients received d4T. Patients who have
      a low body weight and high serum lactate level are at a higher risk of mortality.

PMID- 18337141
TI  - [Accelerated partial breast irradiation in 2008: interrogations and
      perspectives].
AB  - From the beginning of 2000, accelerated and partial breast irradiation (APBI)
      progressively acquired maturity and used more and more sophisticated
      technologies. At this time, at least six international phase III trials are
      ongoing. The statistical design of these studies is elaborated in order to show
      equivalence between APBI and whole breast irradiation (WBI) in term of local
      control. What and when we have to wait from these randomized trials? The
      presented analysis discusses not only the advantages and different interrogations
      concerning APBI, but also the difficulties for radiation oncologists and patients
      to assume the long period until the publication of the ongoing phase III trial
      results. APBI will find its place beside WBI, as well as conservative treatment
      founded its place beside radical mastectomy 30 years ago. However, clinical
      investigation conditions appear now different and this is this difference we have
      to manage rigorously and precisely.

PMID- 18337142
TI  - Acute spontaneous spinal subdural hematoma in a patient with bilateral
      incarcerated inguinal hernia.
AB  - OBJECTIVE: Acute spinal subdural hematoma is an infrequent and devastating
      condition that occurs mostly in patients with coagulopathy or receiving
      anticoagulants. It may also develop after trauma, spinal surgery or
      iatrogenically (lumbar puncture and/or spinal anaesthesia). Spinal vascular
      malformations or spinal tumours can also be the origins of subdural hematomas.
      However, acute spinal subdural hematomas, which are not associated with these
      risk factors, are seen even more infrequently. In this report, we have described
      a case of spontaneous acute spinal subdural hematoma that occurred in a patient
      with bilateral incarcerated inguinal hernia and discussed the possible
      pathomechanisms. METHODS: A 50-year-old male was admitted to the emergency
      department for the acute onset of interscapular pain, slight weakness in both
      legs and urinary retention. Neurological examination revealed paraparesis (3/5 in
      left, 4/5 in right) and hypoesthesia below T5 dermatome. He had long-standing
      bilateral inguinal hernia and constipation for the last 5 days. Magnetic
      resonance imaging of the spine displayed an extramedullary acute hematoma at the
      T4-8 levels but it was impossible to identify whether the hematoma was extradural
      or intradural exactly. The patient underwent an urgent operation via T4-6
      laminectomy. After opening the dura, an extensive, partially organized hematoma
      was completely removed by aspiration. Muscle strength was improved immediately;
      urinary retension was recovered on postoperative day 7. Constipation was relieved
      on postoperative day 4. CONCLUSION: Acute spinal subdural hematoma is an
      emergency condition in case of neurological compromise. Urgent surgical
      evacuation of hematoma results in good outcome. In the case of unidentified
      etiologies, the conditions that could play a role in increased intraabdominal
      and/or intrathoracic pressure should be considered always.

PMID- 18337143
TI  - [The return of the GAS Mask. Reply of P. Berthelot, J.-C. Lucet, S. Aho, J.
      Hajjar to the article by O. Multon ].

PMID- 18337144
TI  - [Cytomegalovirus (CMV) congenital infection].
AB  - Human Cytomegalovirus (CMV) is the main cause of mental retardation and
      sensorineural hearing loss related to congenital infections. Justification of
      systematic screening for fetal CMV infection is still controversial and is not
      recommended in most developed countries. This is mainly justified by the paucity
      of antenatal prognostic factors and the lack of established intrauterine
      treatment when fetal infection has been diagnosed. Our aim was to review the
      current state of the knowledge about the CMV congenital infection and to
      highlight recent advances in the diagnosis as well as in the identification of
      prognostic factors.

PMID- 18337145
TI  - [Vulvar intraepithelial neoplasias (VINs): patients' experience].
AB  - Up to now, there are only a few studies to have dealt with the psychosexual
      consequences of vulvar intraepithelial neoplasias (VINs) and their surgical
      treatment. Yet, these consequences cannot be ignored. The patients' daily
      experience is always complicated, especially because the disease--rightly or not-
      is assimilated to cancer, is a sexually transmissible infection, affects a part
      of the body with particular symbols, but also because today there are no
      certainties whatever on this subject. From the observation of patients followed
      by a team of specialists, this article aims to describe most frequent reactions,
      try to explain them, and consider what medical accompaniment and counsel might be
      proposed in these circumstances.

PMID- 18337146
TI  - [Who should operate on patients with breast cancer?].

PMID- 18337147
TI  - [Effect of magnesium sulphate on mortality and neurologic morbidity of the very
      preterm newborn (of less than 33 weeks) with two-year neurological outcome:
      results of the prospective PREMAG trial].
AB  - OBJECTIVE: To evaluate whether magnesium sulphate (MgSO(4)) given to women at
      risk of very-preterm birth would be neuroprotective in preterm newborns. PATIENTS
      AND METHODS: In 18 French centres, women with fetuses of gestational age less
      than 33 weeks whose birth was expected within 24 hours were randomised from 1993
      to 2003 with follow-up of infants until two years of age after discharge. They
      received a single injection of 0.1 mg/l de MgSO(4) (4g) or isotonic 0.9% saline
      over 30 minutes. This study is registered as an International Standard Randomised
      Controlled Trial, number 00120588. Analyses were based on intention to treat.
      RESULTS: Data from 688 infants were analysed of which 606 were followed up and 10
      were lost to follow-up. Comparing infants who received MgSO(4) or placebo,
      respectively, has shown a decrease of all primary endpoints (total mortality,
      severe white matter injury and their combined outcome) and of all secondary
      endpoints (motor dysfunction, cerebral palsy, cognitive dysfunction and their
      combined outcomes at two years of age) in the MgSO(4) group. The decrease was
      nearly significant or significant for gross motor dysfunction (OR: 0.65 [0.41
      1.02]) and combined criteria: death and cerebral palsy (OR: 0.65 [0.42-1.03]);
      death and gross motor dysfunction (OR: 0.62 [0.41-0.93]); death, cerebral palsy
      and cognitive dysfunction (OR: 0.68 [0.47-1.00]). No major maternal adverse
      effects were observed in the MgSO(4) group. DISCUSSION AND CONCLUSION: Given its
      beneficial effects and safety, the use of prenatal low-dose MgSO(4) for
      preventing neurodisabilities of very-preterm infants should be discussed either
      as a stand-alone treatment or as part of a combination treatment, at least in the
      context of clinical trials.

PMID- 18337148
TI  - [Pertussis vaccine coverage in postpartum women].
AB  - OBJECTIVE: Since July 2006, it has been recommended to give a booster of a
      pertussis vaccine to women just after delivery, if they have received their last
      dose more than 10 years before. The aim of this study was to evaluate the
      pertussis vaccine coverage in a cohort of women just after delivery. PATIENTS AND
      METHODS: All patients (n=31) hospitalized in postpartum unit on the 15th
      September 2006 were included in the study. They were submitted a questionnaire
      and medical records available in the department were reviewed. RESULTS: The
      vaccination coverage was not indicated in any medical records. Only six patients
      claimed they knew their pertussis vaccination status (less than five years: two
      patients, between five and 10 years: two patients, more than 10 years: two
      patients). Two patients had their vaccination booklet. The pertussis vaccine
      coverage is probably very low. DISCUSSION AND CONCLUSION: The information about
      pertussis vaccine status in postpartum women is not available currently because
      it is not recorded by medical team and is unknown by patients themselves. An
      effort in educating obstetricians and corrective actions are necessary if we want
      the recent vaccine schedule to be followed.

PMID- 18337149
TI  - [What are at present the real hopes of pregnancy after ovarian cryopreservation?
      Reply of C. Poirot to the article by B. Courbiere et al ].

PMID- 18337150
TI  - [Use of complementary medicine and supportive care by breast cancer patients].

PMID- 18337151
TI  - Using low intensity ultrasound to improve the efficiency of biological phosphorus
      removal.
AB  - Low intensity ultrasound can produce various effects on biological materials,
      such as stimulating enzyme activity, cell growth, biosynthesis, etc., which may
      improve the efficiency of enhanced biological phosphorus removal (EBPR). We adopt
      total phosphorus (TP) and dehydrogenase activity (DHA) as indicators to confirm
      the feasibility of applying low intensity ultrasound in EBPR. Single-factor
      experiments and orthogonal test were conducted in batch anaerobic/oxic (A/O)
      process simulation to study the influence of ultrasonic intensity and exposure
      time in the EBPR process. The results showed that the optimal ultrasonic
      parameters were 0.2 W/cm2 and 10 min under which condition the TP concentration
      in the effluent was 35-50% lower than that of the control (without ultrasonic
      irradiation). Changes of sludge activities after ultrasonic irradiation were
      examined. The improvement of sludge activity by ultrasound took 4 h after
      irradiation to reach the peak level, when an increase above 50% of DHA has been
      achieved by ultrasonic irradiation, and the enhancing effects induced by
      ultrasound disappeared in 16 h after irradiation. A tentative mechanism of
      biological phosphorus removal enhancement stimulated by ultrasound was discussed
      based on these phenomena.

PMID- 18337152
TI  - Efficacy of botulinum toxin in severe Tourette syndrome with dystonic tics
      involving the neck.
AB  - Severe dystonic tics involving the neck may lead to the development of serious
      spine disease. The pharmacological treatment of tics offers symptomatic relief,
      but clinically relevant improvement of severe tics is not frequently achieved and
      serious adverse events may result. Botulinum toxin (BnT) appears to be a safe and
      effective treatment for tics, but some concern exists about which group of
      patients may benefit from treatment. We report a patient affected by Tourette
      syndrome with tetraparesis and cervical myelopathy secondary to violent dystonic
      tics involving the neck, in which a more aggressive course of treatment with BnT
      in addition to neuroleptic medication resulted in complete resolution of cervical
      tics after 12 months of follow-up.

PMID- 18337153
TI  - Deep brain stimulation of CM/PF of thalamus could be the new elective target for
      tremor in advanced Parkinson's Disease?
AB  - Aim of this study was to investigate whether Deep Brain Stimulation (DBS) of the
      Centre Median Nucleus/Parafascicular (CM/PF) Complex is useful in reducing
      extrapyramidal symptoms in advanced Parkinson's Disease (PD) patients. In
      particular, we compared the action of CM/PF and subthalamic nucleus (STN) DBS on
      resting hand tremor using EMG surface of ulnar and radial right-hand muscles. Our
      results show that C/M DBS is very effective in reducing tremor, indicating this
      complex as a new target in advanced PD patients.

PMID- 18337154
TI  - Plasminogen activator inhibitor type 1 inhibits smooth muscle cell proliferation
      in pulmonary arterial hypertension.
AB  - RATIONALE: Pulmonary arterial smooth muscle cells (PASMCs) in the medial layer of
      the vessel wall are responsible for vessel homeostasis, but also for pathologic
      vascular remodelling in diseases, such as idiopathic pulmonary arterial
      hypertension (IPAH). Vascular remodelling in IPAH results in vessel stiffness,
      occlusion, and increased vascular resistance, but its underlying mechanisms
      remain to be fully elucidated. In this study, we investigated the expression and
      function of plasminogen activator inhibitor (PAI)-1, an inhibitor of the
      plasminogen activator system and target gene of the transforming growth factor
      (TGF)-beta1 signalling cascade, in PASMC in IPAH. METHODS AND RESULTS: RNA and
      protein analysis from lung tissues of donors and patients with IPAH (n=7 each)
      revealed a significant downregulation of PAI-1 in IPAH lungs. Immunohistochemical
      analysis localised PAI-1 to the bronchial and alveolar epithelium, as well as to
      vascular and airway smooth muscle cells. PAI-1 was also downregulated in primary
      PASMC derived from IPAH lungs as compared with donor-derived PASMC. In order to
      elucidate PAI-1 function, primary PASMC were stimulated with active recombinant
      (r)PAI-1, or transfected with PAI-1-specific siRNA. Stimulation with rPAI-1 led
      to decreased PASMC proliferation and adhesion to vitronectin, and increased PASMC
      migration. In contrast, PAI-1 knock-down with siRNA increased PASMC proliferation
      and decreased PASMC migration. CONCLUSIONS: PAI-1 is significantly downregulated
      in PASMC in IPAH, on the mRNA and protein level. PAI-1 negatively regulates PASMC
      proliferation, while it increases PASMC migration. Thus, its loss in IPAH may
      therefore contribute to pathologic vascular remodelling in IPAH.

PMID- 18337155
TI  - GID1-mediated gibberellin signaling in plants.
AB  - Gibberellin (GA) perception is mediated by GID1 (GA-INSENSITIVE DWARF1), a
      receptor that shows similarity to hormone-sensitive lipases. A key event in GA
      signaling is the degradation of DELLA proteins, which are negative regulators of
      GA response that interact with GID1 in a GA-dependent manner. This GID1-DELLA GA
      perception system is conserved among vascular plants but is not found in the moss
      Physcomitrella patens. The identification of factors in GA signaling downstream
      of DELLA and the development of a new concept of DELLA function beyond its role
      as a repressor of GA signaling are important advances. DELLA proteins appear to
      have at least two other distinct roles: maintaining GA homeostasis and regulating
      cross-talk between GA and other plant hormones.

PMID- 18337156
TI  - Maximum distance-gradient for robust image registration.
AB  - To make up for the lack of concern on the spatial information in the conventional
      mutual information based image registration framework, this paper designs a novel
      spatial feature field, namely the maximum distance-gradient (MDG) vector field,
      for registration tasks. It encodes both the local edge information and globally
      defined spatial information related to the intensity difference, the distance,
      and the direction of a voxel to a MDG source point. A novel similarity measure is
      proposed as the combination of the multi-dimensional mutual information and an
      angle measure on the MDG vector field. This measure integrates both the magnitude
      and orientation information of the MDG vector field into the image registration
      process. Experimental results on clinical 3D CT and T1-weighted MR image volumes
      show that, as compared with the conventional mutual information based method and
      two of its adaptations incorporating spatial information, the proposed method can
      give longer capture ranges at different image resolutions. This leads to more
      robust registrations. Around 2000 randomized rigid registration experiments
      demonstrate that our method consistently gives much higher success rates than the
      aforementioned three related methods. Moreover, it is shown that the registration
      accuracy of our method is high.

PMID- 18337157
TI  - Corneal foreign body injury during overnight orthokeratology lens wear: a case
      report.
AB  - PURPOSE: A case of asymptomatic corneal foreign body injury during
      orthokeratology lens wear is reported. CASE REPORT: An 8-year-old Chinese female
      myopic child with 21 months of overnight orthokeratology lens wear experienced a
      corneal foreign body injury without symptoms. The foreign body was removed and
      the eye treated with prophylactic antibiotic and ocular lubricant.
      Orthokeratology treatment was resumed 4 weeks after initial detection and
      management and a small residual corneal scar remained. DISCUSSION: The
      mechanisms, differential diagnoses, management and role of neural sensitivity in
      corneal foreign body injury during orthokeratology lens wear are discussed.
      Clinicians should be aware that subtle corneal insult may be without symptoms
      during prolonged overnight orthokeratology lens wear.

PMID- 18337158
TI  - Striga infestation of cereal crops - an unsolved problem in resource limited
      agriculture.
AB  - The parasitic weed Striga causes devastating losses in cereal yields in sub
      Saharan Africa. The parasite lifecycle is intimately linked with its host via a
      complex interchange of signals. Understanding the molecular basis of these
      interactions and of host resistance to Striga is essential for the identification
      of genes for improving crop yield via biotechnological or marker assisted
      breeding strategies. Cloning and sequencing of ESTs from the 'model' parasite
      Triphysaria versicolor is facilitating the identification of parasitism genes.
      The identification of resistance to Striga in sorghum and rice germplasm is
      allowing molecular dissection of these traits using genomic platforms and
      quantitative trait loci (QTL) analysis. QTL underlying different resistance
      phenotypes have been identified and the use of advanced backcross populations is
      allowing the exploitation of sources of resistance in wild relatives of cereals.

PMID- 18337159
TI  - The cause and consequences of natural variation: the genome era takes off!

PMID- 18337160
TI  - International study of factors affecting human chromosome translocations.
AB  - Chromosome translocations in peripheral blood lymphocytes of normal, healthy
      humans increase with age, but the effects of gender, race, and cigarette smoking
      on background translocation yields have not been examined systematically.
      Further, the shape of the relationship between age and translocation frequency
      (TF) has not been definitively determined. We collected existing data from 16
      laboratories in North America, Europe, and Asia on TFs measured in peripheral
      blood lymphocytes by fluorescence in situ hybridization whole chromosome painting
      among 1933 individuals. In Poisson regression models, age, ranging from newborns
      (cord blood) to 85 years, was strongly associated with TF and this relationship
      showed significant upward curvature at older ages versus a linear relationship
      (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio
      (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the
      effect of age on TFs with a steeper age-related increase among ever smokers
      compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an
      independent effect of race was difficult owing to laboratory variation. Our study
      is three times larger than any pooled effort to date, confirming a suspected
      curvilinear relationship of TF with age. The significant effect of cigarette
      smoking has not been observed with previous pooled studies of TF in humans. Our
      data provide stable estimates of background TF by age, gender, race, and smoking
      status and suggest an acceleration of chromosome damage above age 60 and among
      those with a history of smoking cigarettes.

PMID- 18337161
TI  - Molecular epidemiology of Blastocystis infections in Turkey.
AB  - Blastocystis is a very common unicellular intestinal parasite of ubiquitous
      occurrence. In order to describe the molecular epidemiology of Blastocystis
      infections in Turkey, 87 isolates from 69 symptomatic and 18 asymptomatic
      individuals were sequenced. Sequence data were phylogenetically analyzed and
      statistically tested against unmodifiable risk factors such as gender and age.
      Blastocystis-positive males were complaining mainly of gastroenteritis, whereas
      dyspepsia was the chief complaint among Blastocystis-positive females.
      Blastocystis sp. subtypes detected in the study included subtypes 1, 2, 3 and 4,
      subtype 3 being the most predominant (75.9%). No association was detected between
      Blastocystis sp. subtype and symptoms (p>0.365), or between infection intensity
      and symptoms (p>0.441). There was a tendency of subtype 2 isolates being more
      common among older study individuals, and subtype 2 isolates were significantly
      associated with higher parasite abundance (p=0.017). Compared to data from
      similar studies, the distribution of Blastocystis sp. isolates in Turkey was
      found to more or less reflect the one seen in other countries, and it was deduced
      that subtype 3 is generally by far the most common subtype infecting humans,
      followed by subtypes 1, 2 and 4.

PMID- 18337162
TI  - A spectroelectrochemical study on single-oscillator model and optical constants
      of sulfonated polyaniline film.
AB  - The optical properties of sulfonated polyaniline (SPAN) thin film prepared by
      electrochemical method have been investigated. Polychromic behavior of SPAN thin
      film (transparent yellow-green-dark blue) was observed when the cyclic
      voltammograms were taken between -0.25 V and +1.90 V (vs. Ag/AgCl, sat.) during
      the growth of polyaniline film. In situ UV-vis spectra of the polymers-indium tin
      oxide (ITO) glass electrode were taken during the oxidation of the polymers at
      different applied potentials. The direct band gap values of SPAN thin film
      changed from 3.771 eV to 3.874 eV with the applied potentials. From in situ UV
      vis spectra, the optical constants such as refractive index and dielectric
      constant of the SPAN thin film were determined. The important changes in
      absorption edge, refractive index and the dielectric constant were observed due
      to the applied potentials. The refractive index dispersion curves of the film
      obey the single-oscillator model and oscillator parameters changed with the
      applied potentials. The most significant result of the present work is in situ
      spectroelectrochemical method, which can be used to modify the optical band gaps
      and constants.

PMID- 18337163
TI  - Spectral and thermal studies with anti-fungal aspects of some organotin(IV)
      complexes with nitrogen and sulphur donor ligands derived from 2
      phenylethylamine.
AB  - Some complexes of 2-phenylethyl dithiocarbamate, thiohydrazides and thiodiamines
      with dibenzyltin(IV) chloride, tribenzyltin(IV) chloride and di(para
      chlorobenzyl)tin(IV) dichloride have been synthesized and investigated in 1:2 and
      1:1 molar ratio. The dithiocarbamate ligand act as monoanionic bidentate and
      thiohydrazide, thiodiamines act as neutral bidentate ligand. The synthesized
      complexes have been characterized by elemental analysis and molecular weight
      determination studies and their bonding pattern suggested on the basis of
      electronic, infrared, 1H and 13C NMR spectroscopy. Using thermogravimetric (TG)
      and differential thermal analysis (DTA) various thermodynamic and kinetic
      parameters viz. reaction order (n), apparent activation energy (Ea), apparent
      activation entropy (S#) and heat of reaction (DeltaH) have been calculated and
      correlated with the structural aspects for solid-state decomposition of
      complexes. The ligands and their tin complexes have also been screened for their
      fungitoxicity activity against Rhizoctonia solanii and Sclerotium rolfsii and
      their ED50 values calculated.

PMID- 18337164
TI  - Energy transfer between Er3+:Sm3+codoped TeO2-Li2O glass.
AB  - The energy transfer in Er3+: Sm3+ codoped binary TeO2-Li2O (TLO) glass has been
      studied using 532 nm laser radiation on the basis of fluorescence intensity and
      the lifetime measurements. It is observed that the trace of erbium ion can be
      utilized to sensitize the samarium. The mechanism involved in the present case is
      found to be dipole-dipole. The energy transfer efficiencies, probabilities of
      energy transfer and the average donor acceptor distance has been evaluated.

PMID- 18337165
TI  - EPR parameters and defect structures for the Co2+ ions in LiNbO3 and LiTaO3
      crystals.
AB  - The electron paramagnetic resonance (EPR) parameters (g factors g parallel, g
      perpendicular and hyperfine structure constants A parallel, A perpendicular) for
      Co2+ ions in LiNbO3 and LiTaO3 crystals are calculated from the second-order
      perturbation formulas based on the cluster approach for 3d7 ions in trigonal
      octahedral clusters. The calculated results are in reasonable agreement with the
      experimental values. From the calculations, the negative sign of A parallel for
      Co2+ in the two crystals and the more exact and rational values of A parallel for
      Co2+ in LiTaO3 are suggested. The defect structures (characterized by the Co2+
      displacement DeltaZ along C3 axis and the O(2-) displacement DeltaX in an oxygen
      triangle towards the center of the triangle) for the Co2+ centers in both
      crystals are estimated. The results are discussed.

PMID- 18337166
TI  - Spontaneous resolution of hepatitis C virus infection is not due to a mutation at
      Cys-508 of MAVS/VISA/IPS-1/CARDIF.

PMID- 18337167
TI  - Evaluation of segmental spinal cord evoked magnetic fields after sciatic nerve
      stimulation.
AB  - OBJECTIVE: We have previously reported that the measurement of spinal cord evoked
      magnetic fields (SCEFs) could be a helpful method for evaluating spinal cord
      function or detecting conduction blocks in the spinal cord. However, there have
      been no reports about segmental-SCEFs as a complex of axonal and synaptic
      activities in the spinal cord. The purpose of this study is to record and
      evaluate segmental-SCEFs. METHODS: The segmental-SCEFs were measured over the
      lumbar dural tubes of adult rabbits using our SQUID system following sciatic
      nerve stimulation; spinal cord evoked potentials (SCEPs) were also measured to
      compare the results. RESULTS: SCEPs showed conductive sharp waves following
      gentle waves, suggesting action potentials and synaptic potentials, respectively.
      The isomagnetic field maps of SCEFs showed a quadrupolar pattern propagating from
      the caudal to the cranial region within a short latency time, and after the
      conductive magnetic fields passed, stationary dipolar fields appeared and were
      sustained at some vertebral levels. CONCLUSIONS: The quadrupolar magnetic fields
      were estimated to be generated from conducting action potentials, and the dipolar
      fields were thought to be caused by synaptic activities. SIGNIFICANCE: Through
      the measurement of segmental-SCEFs, the conductive neural and synaptic activities
      in the spinal cord can be visualized and distinguished. This is the first report
      to record and visualize the sequence of events ranging from the axonal activities
      of peripheral nerves and the spinal tract to the synaptic activities in the
      spinal cord.

PMID- 18337168
TI  - EEG indices of tonic pain-related activity in the somatosensory cortices.
AB  - OBJECTIVE: To identify EEG features that index pain-related cortical activity,
      and to identify factors that can mask the pain-related EEG features and/or
      produce features that can be misinterpreted as pain-specific. METHODS: The EEG
      was recorded during three conditions presented in counterbalanced order: a tonic
      cold pain condition, and pain anticipation and arithmetic control conditions. The
      EEG was also recorded while the subjects made a wincing facial expression to
      estimate the contribution of scalp EMG artifacts to the pain-related EEG
      features. RESULTS: Alpha amplitudes decreased over the contralateral temporal
      scalp and increased over the posterior scalp during the cold pain condition.
      There was an increase in gamma band activity during the cold pain condition at
      most electrode locations that was due to EMG artifacts. CONCLUSIONS: The decrease
      in alpha over the contralateral temporal scalp during cold pain is consistent
      with pain-related activity in the primary somatosensory cortex and/or the
      somatosensory association areas located in the parietal operculum and/or insula.
      This study also identified factors that might mask the pain-related EEG features
      and/or generate EEG features that could be misinterpreted as being pain-specific.
      These include (but are not limited to) an increase in alpha generated in the
      visual cortex that results from attention being drawn towards the pain; the
      widespread increase in gamma band activity that results from scalp EMG generated
      by the facial expressions that often accompany pain; and the possibility that non
      specific changes in the EEG over time mask the pain-related EEG features when the
      pain and control conditions are given in the same order across subjects.
      SIGNIFICANCE: This study identified several factors that need to be controlled
      and/or isolated in order to successfully record EEG features that index pain
      related activity in the somatosensory cortices.

PMID- 18337169
TI  - Plasma connective tissue growth factor is a novel potential biomarker of cardiac
      dysfunction in patients with chronic heart failure.
AB  - BACKGROUND: Connective tissue growth factor (CTGF) has been recently reported as
      a mediator of myocardial fibrosis; however, the significance of plasma CTGF
      concentration has not been evaluated in patients with heart failure. The aim of
      this study was to investigate the clinical utility of plasma CTGF concentration
      for the diagnosis of heart failure. METHODS AND RESULTS: We evaluated fifty-two
      patients with chronic heart failure. The plasma concentration of CTGF and other
      markers of fibrosis were assessed and compared with clinical and
      echocardiographic data. Plasma CTGF was significantly elevated in symptomatic
      patients in proportion to their NYHA classes and was significantly correlated
      with plasma brain natriuretic peptide (BNP) concentration (r=0.395, P<0.01).
      Plasma CTGF was also correlated with plasma transforming growth factor beta (TGF
      beta) (r=0.512, P<0.01), matrix metalloproteinase (MMP)-2 (r=0.391, P<0.05) and
      tissue inhibitor of MMP (TIMP)-2 (r=0.354, P<0.05) concentrations. Interestingly,
      plasma CTGF was correlated with E/E' value evaluated by tissue Doppler
      echocardiography (r=0.593, P=0.012), but not with systolic function and left
      ventricular mass. CONCLUSION: Our study suggests that plasma CTGF concentration
      is a novel diagnostic marker for cardiac dysfunction and may provide additional
      specific information about myocardial fibrosis in chronic heart failure patients.

PMID- 18337170
TI  - The influence of storage and leukocyte depletion on the antigen densities of FY1,
      FY2, MNS3 and MNS4 measured by flow cytometry.
AB  - Red blood cell (RBC) antigens may present changes in density during storage and
      leukocyte reduction. We evaluated the influence of these variables on FY1, FY2,
      MNS3 and MNS4 antigens using quantitative flow cytometry (FCM). Forty-eight RBC
      units were divided into two sub-units each immediately after collection. One of
      them was leukocyte reduced before storage. Antigen expression was analyzed on
      days 1 and 35 of storage by gel-centrifugation and FCM. Three RBC samples were
      submitted to papain and bromelin treatment. The gel-centrifugation test could not
      detect any influence of storage or leukocyte reduction. However, by FCM, a wide
      variation of antigen density among the donors was found. Leukocyte depletion did
      not change the antigen density but after storage, expression of FY1 and MNS4
      showed a slight decrease. Median antigenic density of FY1 was 11,332 in FY1,2 and
      23,436 in FY1,-2 donors. FY2 presented 7204 and 7868, respectively. MNS4 had
      100,589 and 214,340 sites in donors MNS3,4 and MNS-3,4, respectively, and MNS3
      had 10,389 and 21,122 sites, respectively. After enzyme treatments none of the
      antigens could be detected. FCM was a reproducible technique, suitable for the
      quantification of the antigens studied in RBC concentrates stored and leukocyte
      reduced in conditions normally used for blood transfusion.

PMID- 18337171
TI  - Platelet apheresis affects prothrombin time and fibrinogen and plasminogen levels
      in healthy donors.

PMID- 18337173
TI  - A possible role of histone-like DNA-binding protein of Streptococcus intermedius
      in the pathogenesis of bile duct damage in primary biliary cirrhosis.
AB  - Bacterial infection has become a focus of attention in the pathogenesis of
      primary biliary cirrhosis (PBC). It was reported that anti-histone autoantibody
      was detected in PBC, suggesting that bacterial histone-like DNA-binding protein
      (HLP) may be involved in the pathogenesis of PBC. To identify bacterial species
      in PBC to confirm this possibility, serum reactivity to bacterial cells was
      studied by ELISA. The IgM class Streptococcus intermedius titers were
      significantly higher in PBC than chronic hepatitis due to hepatitis C virus (CH
      C) and healthy subjects. Among the streptococci, S. intermedius was selected for
      further study. The antigenic peptide of S. intermedius of HLP was synthesized to
      examine the serum reactivity to Si-HLP. IgM class anti-Si-HLP peptide titers were
      significantly higher in PBC. Immunoreactivity to anti-Si-HLP was detected in the
      cytoplasm of biliary epithelial cells and inflammatory cells in the portal area
      in PBC patients' livers. Streptococci, especially S. intermedius, might play a
      key role in the pathogenesis of PBC, possibly involving HLP.

PMID- 18337172
TI  - Tissue-targeted therapy of autoimmune diabetes using dendritic cells transduced
      to express IL-4 in NOD mice.
AB  - A deficit in IL-4 production has been previously reported in both diabetic human
      patients and non-obese diabetic (NOD) mice. In addition, re-introducing IL-4 into
      NOD mice systemically, or as a transgene, led to a beneficial outcome in most
      studies. Here, we show that prediabetic, 12-week old female NOD mice have a
      deficit in IL-4 expression in the pancreatic lymph nodes (PLN) compared to age
      matched diabetes-resistant NOD.B10 mice. By bioluminescence imaging, we
      demonstrated that the PLN was preferentially targeted by bone marrow-derived
      dendritic cells (DCs) following intravenous (IV) administration. Following IV
      injection of DCs transduced to express IL-4 (DC/IL-4) into 12-week old NOD mice,
      it was possible to significantly delay or prevent the onset of hyperglycemia. We
      then focused on the PLN to monitor, by microarray analysis, changes in gene
      expression induced by DC/IL-4 and observed a rapid normalization of the
      expression of many genes, that were otherwise under-expressed compared to NOD.B10
      PLN. The protective effect of DC/IL-4 required both MHC and IL-4 expression by
      the DCs. Thus, adoptive cellular therapy, using DCs modified to express IL-4,
      offers an effective, tissue-targeted cellular therapy to prevent diabetes in NOD
      mice at an advanced stage of pre-diabetes, and may offer a safe approach to
      consider for treatment of high risk human pre-diabetic patients.

PMID- 18337174
TI  - Rituximab-induced B cell depletion in autoimmune diseases: potential effects on T
      cells.
AB  - Peripheral B cell depletion strategies have been employed recently in the
      treatment of systemic autoimmune diseases and the initial clinical results have
      been encouraging. Although the major target of rituximab-based treatments was to
      reduce the levels of circulating autoantibodies, additional mechanisms of action
      may operate. Recent studies have addressed the question of potential effects of
      transient B cell depletion on other, non-B cell populations. The data, albeit
      uncontrolled, suggest that anti-CD20 monoclonal antibody treatment is associated
      with significant effects in the T cell pool, whereas individual clinical
      responses do not always correlate with changes in autoantibody titers. More
      specifically, it has been reported that rituximab administration may decrease the
      activated phenotype of peripheral and tissue-resident T cells by abolishing
      antigen presentation by B cells, and may enhance the numbers and function of
      regulatory T cells. In this review we analyze and discuss available data emerging
      from B cell depletion studies in patients with systemic lupus erythematosus,
      rheumatoid arthritis and other autoimmune conditions. Further controlled studies
      are needed to confirm the role of B cell depletion in modifying T cell function
      in vivo.

PMID- 18337175
TI  - Contribution of influenza immunity and virosomal-formulated synthetic peptide to
      cellular immune responses in a phase I subunit malaria vaccine trial.
AB  - We have demonstrated recently in a phase Ia clinical trial that synthetic malaria
      peptides delivered by immuno-potentiating reconstituted influenza virosomes
      (IRIV) induced long-lived peptide-specific antibody responses in all volunteers.
      In the current ancillary study to this clinical trial we have investigated the
      cellular immune responses specific for IRIV and the surface bound synthetic
      malaria peptides tested. After vaccination, in 50% (8/16) of the volunteers at
      least one positive lymphoproliferative response specific for the 49mer peptide
      derived from the Plasmodium falciparum apical membrane antigen-1 (AMA-1) was
      observed with stimulation indices ranging from 2 to 4.5. All volunteers showed
      pre-existing IRIV specific cellular immunity assessed by ex vivo IFN-gamma
      ELISpot analysis and lymphoproliferation. The pre-existing influenza specific T
      cell responses did not interfere negatively with the induction of malaria peptide
      specific humoral and cellular immune responses. Our results support the view that
      IRIV constitute a safe antigen delivery system for induction of peptide-specific
      immune responses in human populations.

PMID- 18337176
TI  - Treatment with an apolipoprotein A-1 mimetic peptide in combination with
      pravastatin inhibits collagen-induced arthritis.
AB  - To evaluate the therapeutic potential of an apolipoprotein A-1 (apoA-1) mimetic
      peptide, D-4F, in combination with pravastatin in collagen-induced arthritis
      (CIA), syngeneic Louvain rats were immunized with type II collagen and randomized
      to vehicle control, D-4F monotherapy, pravastatin monotherapy, or D-4F +
      pravastatin combination therapy. Clinical arthritis activity was evaluated and
      radiographs, type II collagen antibody titers, cytokine/chemokine levels, and HDL
      function analysis were obtained. There was significant reduction in clinical
      severity scores in the high and medium dose D-4F + pravastatin groups compared to
      controls (p< or =0.0001). Reduction in erosive disease occurred in the
      medium/high dose combination groups compared to non-combination groups (p< or
      =0.01). Favorable changes in cytokines/chemokines were noted with treatment, and
      response to combination D-4F/pravastatin therapy was associated with improvement
      in HDL's anti-inflammatory properties. Combination D-4F/pravastatin significantly
      reduced clinical disease activity in CIA, and may have dual therapeutic potential
      in other autoimmune diseases with increased cardiovascular morbidity and
      mortality.

PMID- 18337177
TI  - Reviewing maternal deaths to make pregnancy safer.
AB  - Every year, some eight million women around the world suffer pregnancy-related
      complications; over half a million of these women die. Although most of these
      deaths could be averted at little or no extra cost, even where resources are
      limited, if we are to take action and develop and implement changes to maternity
      services to save the lives of mothers and newborns, we need the right kind of
      information. This more in-depth information might not be available through
      national statistics on maternal mortality rates or death certificate data; what
      is required is a detailed understanding of the clinical, social, cultural and
      other underlying factors that result in a mother's death. The World Health
      Organization's programme and philosophy for such maternal death or disability
      reviews is called Beyond the numbers. It outlines the five key methodologies for
      reviewing maternal deaths or disabilities that are now being introduced in a
      number of countries around the world.

PMID- 18337178
TI  - Amygdaloid kindling is anxiogenic but fails to alter object recognition or
      spatial working memory in rats.
AB  - Kindling in rats produces enduring behavioral changes that parallel the
      psychobehavioral disturbances frequently accompanying temporal lobe epilepsy.
      Some evidence suggests that the site of kindling is an important determinant of
      the type of behavioral changes observed following kindling, although this
      variable has not been systematically investigated. In the present experiments,
      the effects of amygdaloid kindling were assessed on a battery of behavioral tests
      we used previously to assess the effects of kindling in dorsal hippocampus or
      perirhinal cortex. Three generalized seizures were kindled with stimulation in or
      near the basolateral amygdala. One week later, rats were tested successively on
      measures of anxiety, activity, object recognition memory, and spatial working
      memory over a period of 3 weeks. Amygdaloid kindling produced increased anxiety,
      but spared all other behaviors assessed. This pattern of results is partially
      distinct from the previously described effects of perirhinal cortical kindling,
      which increases anxiety but also impairs object recognition memory, and is
      completely distinct from dorsal hippocampal kindling, which selectively increases
      activity and impairs spatial working memory. The observations suggest that
      kindling of distinct highly interconnected temporal lobe sites produces distinct
      patterns of behavioral comorbidity. The underlying mechanisms are thus most
      likely localized to intrinsic circuits at the site of seizure origination.

PMID- 18337179
TI  - Effective treatments of prolonged status epilepticus in developing rats.
AB  - We determined the efficacy of diazepam (DZP) and pentobarbital (PTB) in
      controlling prolonged status epilepticus (SE) in developing rats. One-hour-long
      SE was induced with kainic acid (KA) or lithium pilocarpine (Li-Pilo) in
      Postnatal Day 9 (P9), 15 (P15) and 21 (P21) rats, which were then treated with
      varying doses of DZP (20-60 mg/kg) or PTB (20-60 mg/kg). At P9, neither drug
      stopped SE, and higher doses could not be used because of high mortality. At P15
      and P21, DZP and PTB stopped both behavioral and electrographic SE in a dose
      dependent fashion, with similar efficacy in the two seizure models. DZP stopped
      SE significantly faster than PTB. Administration of a low dose of PTB (20mg/kg)
      following an initially ineffective treatment with DZP 20mg/kg stopped SE in all
      rats. The data suggest that high doses of DZP and PTB are needed to stop
      prolonged SE in developing rats, but their effectiveness is age dependent.

PMID- 18337180
TI  - A survey of neurologists' views on epilepsy surgery and medically refractory
      epilepsy.
AB  - There is a 20-year delay between the diagnosis of epilepsy and surgical
      treatment. The aim of this study was to describe the different views held by
      neurologists regarding refractory epilepsy that may contribute to the delay in
      referring patients for epilepsy surgery. Neurologists in Michigan were mailed a
      10-item survey inquiring about their definition of medically refractory epilepsy
      and their decision-making process in referring patients for epilepsy surgery.
      Eighty-four neurologists responded (20%). The majority defined medically
      refractory epilepsy as failure of three monotherapy antiepileptic drug (AEDs)
      trials and at least two polytherapy trials. Nineteen percent responded that all
      approved AEDs had to fail before a patient could be defined as medically
      refractory. Eighty-two percent of the respondents had referred patients for
      epilepsy surgery. Almost 50% were not satisfied with the level of communication
      from epilepsy centers. One-third reported serious complications resulting from
      surgery. These findings suggest that further education and improved communication
      from comprehensive epilepsy centers may shorten the time to referral and
      ultimately improve the lives of patients with epilepsy.

PMID- 18337181
TI  - Behavioral characterization of pentylenetetrazol-induced seizures in the
      marmoset.
AB  - This study was designed to characterize seizures induced with pentylenetetrazol
      (PTZ) in marmosets. Thirteen adult marmosets (Callithrix sp.) received 20, 30, or
      40 mg/kg of PTZ intraperitoneally. PTZ caused all animals to switch their natural
      behavioral repertoire to early convulsive behavior. Seizure scores were low at
      lower PTZ doses, whereas the highest dose of PTZ led to seizure scores IV and V
      (according to Racine's scale) in 69% of animals. To further characterize the
      model we performed a preliminary evaluation of the efficacy of three
      antiepileptic drugs: phenobarbital, phenytoin, and carbamazepine. Phenobarbital
      prevented PTZ-induced seizures in 100% of trials. As expected, phenytoin and
      carbamazepine were not effective against PTZ-induced seizures. The present study
      describes the PTZ model of seizures in marmosets with a drug-response profile
      similar to that of the rodent model, thus bringing to a well-known model (PTZ in
      rodents) the complexity of a nonhuman primate brain.

PMID- 18337182
TI  - Parenting stress in mothers of children with intractable epilepsy.
AB  - OBJECTIVE: The goal of the work described here was to determine the prevalence
      and characteristics of maternal stress in families of children with intractable
      epilepsy. METHODS: Mothers of children aged 2-18 with intractable epilepsy were
      asked to complete the Parenting Stress Index, Scales of Independent Behavior
      Revised, and Child Behavior Checklist, and were queried regarding family type,
      maternal education, and family income. Neurology clinic charts were reviewed for
      seizure variables including age at onset, number of failed therapies, and seizure
      frequency. The Parenting Stress Index measures stress in two broad domains
      [stress related to characteristics of the child (Child Domain) and stress related
      to characteristics of the parent (Parent Domain)] as well as a Total Stress
      score. RESULTS: Fifty-two of 80 (65%) eligible mothers returned completed
      questionnaires. Sixty-three percent scored in the clinical range for Total
      Stress, 75% for the Child Domain, but only 29% for the Parent Domain. Mothers
      scored more adversely on the Isolation, Health, Role Restriction, and Spouse
      subscales of the Parent Domain, but more favorably on the Attachment subscale. A
      moderate to high correlation was noted between behavior problems in the child and
      higher Total Stress scores, but no significant correlations were found between
      other seizure or demographic variables. CONCLUSION: Intractable childhood
      epilepsy is associated with markedly increased maternal parenting stress.
      Increased stress is due predominantly to child factors. Mothers would strongly
      benefit from added support to alleviate the constant caregiving demands.

PMID- 18337183
TI  - Further development of the multidimensional pain readiness to change
      questionnaire: the MPRCQ2.
AB  - This study describes further development of the Multidimensional Pain Readiness
      to Change Questionnaire (MPRCQ2), a measure of readiness to adopt a variety of
      pain management and coping strategies commonly taught in multidisciplinary
      treatment programs. Clinical samples were recruited from a Fibromyalgia Day
      Program (n = 139) and an Arthritis Day Program (n = 51) as well as 2 survey
      samples with pain resulting from either a spinal cord injury (n = 127) or an
      amputation (n = 120). The results indicate preliminary support for the
      reliability and validity of the MPRCQ2. The MPRCQ2 may be helpful in future
      research investigating the relationship between readiness to change pain-related
      coping and adoption of coping behaviors and adjustment to chronic pain.
      PERSPECTIVE: This study describes the development of a revised version of the
      MPRCQ, the MPRCQ2, in 4 patient samples. The results support the reliability and
      validity of the MPRCQ2 in individuals with fibromyalgia syndrome, arthritis,
      acquired amputation, and spinal cord injury and improve on some aspects of the
      instrument.

PMID- 18337184
TI  - Central pituitary adenylate cyclase 1 receptors modulate nociceptive behaviors in
      both inflammatory and neuropathic pain states.
AB  - The pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC(1)-R)
      is a member of the 7-transmembrane domain, group 2 G-protein coupled receptor
      family. PAC(1)-Rs modulate neurotransmission and neurotrophic actions and have
      been implicated in both pronociception and antinociception. To better understand
      the role of PAC(1)-Rs in pain, PACAP 6-38, a PAC(1)-R antagonist, was evaluated
      in several inflammatory and neuropathic pain models after intrathecal (i.t.)
      administration. PACAP 6-38 potently reduced mechanical allodynia in a neuropathic
      spinal nerve ligation model (77% +/- 15% maximal effect at 12 nmol, P < .01) and
      was also effective in reducing thermal hyperalgesia in the carrageenan model of
      inflammatory pain (89% +/- 17% maximal effect at 12 nmol, P < .01). Although
      nociceptive responses were also attenuated with PACAP 6-38 in a dose-dependent
      manner in models of chronic inflammatory and persistent pain, no effects on motor
      performance were observed at analgesic doses. Taken together, these data
      demonstrate that blockade of the PAC(1)-R/PACAP complex by PACAP 6-38 can
      effectively attenuate thermal hyperalgesia and mechanical allodynia associated
      with inflammatory and neuropathic pain states. These results further emphasize
      that at the level of the spinal cord, PAC(1)-R activation is pronociceptive.
      PERSPECTIVE: This article presents the analgesic profile generated by the
      blockade, at the spinal cord level, of the PAC-1 receptor by a potent peptide
      antagonist. This comprehensive data set demonstrates that if small molecule PAC-1
      receptor antagonists could be identified, they would potentially produce broad
      spectrum analgesia in both inflammatory and neuropathic pain states.

PMID- 18337185
TI  - Characterization of a model of chronic orofacial hyperalgesia in the rat:
      contribution of NA(V) 1.8.
AB  - The purpose of this study was to develop and characterize a model of orofacial
      inflammatory hyperalgesia. Injection of complete Freund's adjuvant (CFA) into the
      upper lip/whisker pad of the rat produced significant and long-lasting thermal (>
      or =14 days) and mechanical (> or =28 days) hyperalgesia in the area of CFA
      injection. Both indomethacin and morphine, given systemically, significantly
      attenuated thermal hyperalgesia; the effect of morphine was shown to be opioid
      receptor-mediated. We also examined the contribution of the tetrodotoxin
      resistant voltage-gated sodium channel Na(v)1.8 in CFA-produced orofacial
      mechanical hypersensitivity. Na(v)1.8 mRNA was increased > or =2.5-fold in
      trigeminal ganglion neurons 1 and 2 weeks after CFA treatment, and Na(v)1.8
      protein was increased in the infraorbital nerve over a similar time course. The
      changes observed were time-dependent and had returned to baseline when examined 2
      months after inflammation; there were no changes in Na(v)1.9 mRNA in trigeminal
      ganglion neurons after CFA treatment. In support of this, Na(v)1.8 antisense
      oligodeoxynucleotide treatment significantly attenuated CFA-produced mechanical
      hypersensitivity. These results document development of a model of inflammatory
      orofacial hyperalgesia, which, consistent with other reports, indicate a
      contribution of tetrodotoxin-resistant, voltage-gated sodium channel Na(v)1.8.
      PERSPECTIVE: Orofacial hypersensitivity develops postoperatively as a routine
      course of orofacial surgery, and mechanical allodynia is characteristic of
      temporomandibular joint disorder. The results described in this report are novel
      with respect to the duration of orofacial hypersensitivity produced and suggest
      that pharmacological targeting of the voltage-gated sodium channel Na(v)1.8 may
      be useful in managing hypersensitivity.

PMID- 18337186
TI  - Perioperative pain management in the opioid-tolerant individual.

PMID- 18337187
TI  - Cloning and mRNA expression of antioxidant enzymes in the Pacific oyster,
      Crassostrea gigas in response to cadmium exposure.
AB  - Cadmium (Cd) is one of the most toxic heavy metal pollutants in the aquatic
      environment and can induce the formation of reactive oxygen species (ROS) that
      cause oxidative stress. In present study, we cloned catalase (CAT) and
      glutathione peroxidase (GPX) cDNA, and investigated its time- and dose-related
      effects of three Cd concentrations (0.01, 0.05 or 0.1 ppm) on mRNA levels of
      antioxidant enzymes (superoxide dismutase (SOD), CAT, GPX) in the gill and
      changes enzyme levels in the hemolymph of the Pacific oyster, Crassostrea gigas.
      The cDNA indentified encoded proteins of 516 and 244 amino acids corresponding to
      CAT and GPX, respectively. BLAST analysis from other species indicated that the
      residues essential to the enzymatic function of CAT and GPX proteins of C. gigas
      are highly conserved. Cd treatment significantly increased antioxidant enzyme
      mRNA expression in the gill in a time- and dose-dependent manner. The mRNA
      expression at 0.1 ppm Cd concentration increased up to 3 days (CAT, GPX) or 7
      days (SOD) and then decreased by 7 days (CAT, GPX) or 11 days (SOD). Aspartate
      aminotransferase, alanine amintransferase and hydrogen peroxide (H(2)O(2))
      concentrations levels increased significantly with exposure to 0.05 or 0.1 ppm Cd
      for 7 days. These results suggest that antioxidant enzymes play important roles
      in the physiological changes related to metabolism and cell protection that occur
      in Pacific oysters exposed to Cd.

PMID- 18337188
TI  - Dynamic Bayesian networks as prognostic models for clinical patient management.
AB  - Prognostic models in medicine are usually been built using simple decision rules,
      proportional hazards models, or Markov models. Dynamic Bayesian networks (DBNs)
      offer an approach that allows for the incorporation of the causal and temporal
      nature of medical domain knowledge as elicited from domain experts, thereby
      allowing for detailed prognostic predictions. The aim of this paper is to
      describe the considerations that must be taken into account when constructing a
      DBN for complex medical domains and to demonstrate their usefulness in practice.
      To this end, we focus on the construction of a DBN for prognosis of carcinoid
      patients, compare performance with that of a proportional hazards model, and
      describe predictions for three individual patients. We show that the DBN can make
      detailed predictions, about not only patient survival, but also other variables
      of interest, such as disease progression, the effect of treatment, and the
      development of complications. Strengths and limitations of our approach are
      discussed and compared with those offered by traditional methods.

PMID- 18337189
TI  - Evolution and challenges in the design of computational systems for triage
      assistance.
AB  - Compared with expert systems for specific disease diagnosis, knowledge-based
      systems to assist decision making in triage usually try to cover a much wider
      domain but can use a smaller set of variables due to time restrictions, many of
      them subjective so that accurate models are difficult to build. In this paper, we
      first study criteria that most affect the performance of systems for triage
      assistance. Such criteria include whether principled approaches from machine
      learning can be used to increase accuracy and robustness and to represent
      uncertainty, whether data and model integration can be performed or whether
      temporal evolution can be modeled to implement retriage or represent medication
      responses. Following the most important criteria, we explore current systems and
      identify some missing features that, if added, may yield to more accurate triage
      systems.

PMID- 18337190
TI  - Consensus and Meta-analysis regulatory networks for combining multiple microarray
      gene expression datasets.
AB  - Microarray data is a key source of experimental data for modelling gene
      regulatory interactions from expression levels. With the rapid increase of
      publicly available microarray data comes the opportunity to produce regulatory
      network models based on multiple datasets. Such models are potentially more
      robust with greater confidence, and place less reliance on a single dataset.
      However, combining datasets directly can be difficult as experiments are often
      conducted on different microarray platforms, and in different laboratories
      leading to inherent biases in the data that are not always removed through pre
      processing such as normalisation. In this paper we compare two frameworks for
      combining microarray datasets to model regulatory networks: pre- and post
      learning aggregation. In pre-learning approaches, such as using simple scale
      normalisation prior to the concatenation of datasets, a model is learnt from a
      combined dataset, whilst in post-learning aggregation individual models are
      learnt from each dataset and the models are combined. We present two novel
      approaches for post-learning aggregation, each based on aggregating high-level
      features of Bayesian network models that have been generated from different
      microarray expression datasets. Meta-analysis Bayesian networks are based on
      combining statistical confidences attached to network edges whilst Consensus
      Bayesian networks identify consistent network features across all datasets. We
      apply both approaches to multiple datasets from synthetic and real (Escherichia
      coli and yeast) networks and demonstrate that both methods can improve on
      networks learnt from a single dataset or an aggregated dataset formed using a
      standard scale-normalisation.

PMID- 18337191
TI  - Direct electron-transfer of native hemoglobin in blood: kinetics and catalysis.
AB  - A novel approach that uses nature biological tissues, fish blood, for the study
      of the direct electron-transfer of hemoglobin and its catalytic activity for
      H(2)O(2) and NO(2)(-) is observed. The direct electron-transfer of hemoglobin in
      red blood cells in fish blood on glassy carbon electrode was observed for the
      first time. By simply casting fish blood on GC electrode surface and being air
      dried, a pair of well-defined redox peaks for HbFe (III)/HbFe (II) appeared at
      about -0.36 V (vs SCE) at the fish blood film modified GCE in a pH 7.0 phosphate
      buffer solution. Ultraviolet visible (UV/VIS) characterization and the
      enhancement of the redox response of Hb by adding pure Hb in fish blood suggested
      that Hb preserved the native second structures in the fish blood film. Optical
      micrographs showed that the RBCs retained its integrity in blood. Hb in blood/GCE
      maintained its activity and could be used to electrocatalyze the reduction
      H(2)O(2) and NO(2)(-).

PMID- 18337192
TI  - Rearrangements in the flanking sequences of the triplet repeat of the FMR1 gene
      give clues to the mechanisms involved in repeat instability in fragile X.

PMID- 18337193
TI  - Restoration of hemodynamics in apnea struggle phase in association with
      involuntary breathing movements.
AB  - Involuntary breathing movements (IBM) that occur in the struggle phase of maximal
      apneas produce waves of negative intrathoracic pressure. This could augment the
      venous return, increasing thereby the cardiac output and gas exchange, and
      release the fresh blood from venous pools of spleen and liver. To test these
      hypotheses we used photoplethysmography and ultrasound for assessment of
      hemodynamics and spleen size before, during and after maximal dry apneas at large
      lung volume in 7 trained divers. During the easy-going phase cardiac output was
      reduced about 40%, due to reduction in stroke volume and in presence of reduced
      inferior vena cava venous return, while the spleen contracted for about 60 ml.
      Towards the end of the struggle phase, in presence of intense IBM, the spleen
      volume further decreased for about 70 ml, while cardiac output and caval flow
      almost renormalized. In conclusion, IBM coincide with splenic volume reduction
      and restoration of hemodynamics, likely facilitating the use of the last oxygen
      reserves before apnea cessation.

PMID- 18337194
TI  - Percutaneous and surgical treatment of pyogenic liver abscesses: observation over
      a 21-year period in 148 patients.
AB  - BACKGROUND: Percutaneous drainage of pyogenic liver abscess has become first-line
      treatment. In the past surgical drainage was preferred in some centres. AIM: The
      aim of this retrospective study was to assess the effectiveness of percutaneous
      treatments and surgical drainage, in terms of treatment success, hospital stay
      and costs. PATIENTS: Data of 148 patients (90 males; 58 females; mean age, 61
      yrs; range, 30-86 yrs) were retrospectively analysed. METHODS: Patients'
      outcomes, including the length of hospital stay, procedure-related complications,
      treatment failure and death, were recorded. Multiple logistic regression model
      was used for statistical analysis. RESULTS: One hundred and four patients (83
      with solitary and 21 with multiple abscesses) were treated percutaneously, either
      by needle aspiration (91 patients) or catheter drainage (13 patients) depending
      on the abscess's size, and 44 patients (30 with solitary and 14 with multiple
      abscesses) were treated surgically. There was no statistically significant
      difference in patients' demographics or abscess characteristics between groups.
      Hospital stay was longer, and costs were higher in patients treated surgically
      (p<0.001). There was statistically significant difference in morbidity rate
      between groups (p<0.001). No death occurred in both groups. CONCLUSIONS:
      Percutaneous and surgical treatment of pyogenic liver abscesses are both
      effective, nevertheless percutaneous drainage carries lower morbidity and is
      cheaper.

PMID- 18337195
TI  - Ferroportin-1 in the recurrence of hepatic iron overload after liver
      transplantation.
AB  - Hepatic siderosis is frequent in patients with Hepatitis C virus (HCV) chronic
      hepatitis and considered secondary to advanced liver disease when detected in the
      explanted liver of cirrhotic patients submitted to transplantation. Here, we
      document the early recurrence of hepatic iron overload starting from host Kupffer
      cells and later involving hepatocytes in an Italian male submitted to liver
      transplantation for HCV-related cirrhosis, whose hemosiderosis was interpreted as
      related to a primary defect of iron handling by monocytic cells due to decreased
      Ferroportin-1 expression. He was negative for HFE mutations, had normal liver
      function, did not drink alcohol and had no erythropoietic defect. He was positive
      for the (CGG)(8/9) and the IVS1 -24 G>C Ferroportin-1 polymorphisms, associated
      with non-parenchymal iron overload, and had decreased Ferroportin-1 expression in
      monocytes. In conclusion, this case report documents the recurrence of
      progressive liver siderosis, which recalls Ferroportin disease, associated with
      decreased Ferroportin-1 expression in host monocytes repopulating the donor
      liver.

PMID- 18337196
TI  - Social learning theory and cognitive behavioral models of body dysmorphic
      disorder.
AB  - Contemporary cognitive behavioral models of body dysmorphic disorder are
      reviewed, whereby the first by Neziroglu and colleagues emphasizes conditioning
      processes and relational frame theory and the latter by Veale emphasizes
      information processing. A brief review of the existing cognitive behavioral
      therapy research follows the presentation of the models. The majority of
      publications on BDD continue to deal with phenomenology and epidemiology, and
      much more research on cognitive behavioral treatment is needed. Treatment
      research should be geared towards testing elements of the models explicated in
      this article, and randomized controlled trials are greatly needed.

PMID- 18337197
TI  - Hyper-branched poly(poly(ethylene glycol)methacrylate)-grafted surfaces by photo
      polymerization with iniferter for bioactive interfaces.
AB  - A new hyper-branched surface in which three species of architectures were
      constructed as stem chain, branched stem and twig chain-grafted branched chain of
      poly(poly(ethylene glycol)methacrylate) (poly(PEGMA)) by photo-polymerization
      using dithiocarbamyl group (DC) as iniferter was prepared and characterized. For
      these surfaces, radical copolymerization of styrene and an iniferter-activated
      chain that was previously synthesized was performed for using as base materials
      for surface coating. On a DC-activated surface, hyper-branched poly(PEGMA) was
      introduced by photo-polymerization and dithiocarbamylation. All modified surfaces
      were analyzed by X-ray photoelectron spectroscopy (XPS) and water contact angle
      measurements. Our results demonstrated that a highly hyper-branched graft
      architecture of poly(PEGMA) can be constructed on PU surface by photo
      polymerization using dithiocarbamyl group as iniferter, in which first, second
      and third generation gave stem chain, branched chain and twig chain of
      poly(PEGMA), respectively. Our hyper-branched surfaces could be regulated by
      photo-irradiation time and might be controlled by feed amounts or other reaction
      conditions. This highly dense architecture of PEG chain with hydrophilicity and
      chain mobility, grafted on surface, is expected to be effectively utilized in bio
      implantable substrates or micro- or nano-patterned surfaces for immobilization of
      bioactive molecules in biomedical fields.

PMID- 18337198
TI  - Drug release behavior of chitosan-montmorillonite nanocomposite hydrogels
      following electrostimulation.
AB  - Nanocomposites hydrogel (nanohydrogel) composed of chitosan (CS) and
      montmorillonite (MMT) were prepared and systematically studied for drug release
      behavior following electrostimulation. The deterioration of the responsiveness
      and reversibility of CS upon repeated on-off electrostimulation switching
      operations are major limitations for clinical applications, as it suffers from
      too much structural instability for the precise control of the release of drug
      upon cyclic electrostimulation. To overcome these limitations, an inorganic
      phase, MMT, was incorporated in the CS matrix to enhance the anti-fatigue
      property and corresponding long-term stable release kinetics. X-ray diffraction
      analysis and time-dependent optical absorbance showed that the MMT incorporated
      into the nanohydrogel exhibited an exfoliated nanostructure. The exfoliated
      silica nanosheets are able to act as cross-linkers to form a network structure
      between the CS and MMT, and this difference in the cross-linking density strongly
      affects the release of vitamin B(12) under electrostimulation. With a lower MMT
      concentration (1 wt.%), the release kinetics of vitamin B(12) from the
      nanohydrogel shows a pseudo-zero-order release, and the release mechanism was
      changed from a diffusion-controlled mode to a swelling-controlled mode under
      electrostimulation. Further increasing the MMT content reduced both the diffusion
      exponent n and the responsiveness of the nanohydrogel to electrostimulation. In
      addition, a consecutively repeated "on" and "off" operation shows that the
      electroresponsiveness of the nanohydrogel with higher MMT concentrations was
      reduced, but its anti-fatigue behavior was considerably improved. In this work,
      the nanohydrogel with 2 wt.% MMT achieved a mechanically reliable and practically
      desirable pulsatile release profile and excellent anti-fatigue behavior, compared
      with that of the pure CS.

PMID- 18337199
TI  - Outcomes of modular proximal femoral replacement in the treatment of complex
      proximal femoral fractures: a case series.
AB  - BACKGROUND: The treatment of complex femur fractures poses a significant
      challenge. Even with current advancements and the various implements available
      for the fixation of femoral fractures, results are often disappointing. This
      study sought to identify problems associated with and examine results of modular
      proximal femoral replacement. Outcomes were evaluated in two groups of patients:
      those receiving primary modular proximal femoral replacement for fractures and
      those treated with salvage arthroplasty for failed internal fixation. METHODS:
      Twelve patients who had received modular proximal femoral replacement as primary
      treatment for proximal femoral fractures were evaluated along with nine patients
      treated with salvage proximal femoral replacement for failed internal fixation.
      After the surgical procedure, patients were evaluated at regular follow-up
      intervals and contacted by phone at the conclusion of this study. Patient
      functional results were evaluated using the Merle D'Aubigne hip rating scale,
      which measures pain, motion and ambulatory status. Routine radiographs were also
      obtained at each patient visit. RESULTS: On average, patients who received
      modular proximal femoral replacement as the primary surgery for their femoral
      fractures enjoyed a high-level functional result and had few complications.
      Subjects who received salvage femoral replacement had a less optimal outcome and
      experienced more complications. Nonetheless, final post-operative MDA score was
      significantly increased from pre-operative levels. CONCLUSION: Modular proximal
      femoral replacement is a viable option in the primary fracture or revision
      setting, and has been shown to have a reasonable outcome, especially when the
      nature of initial injury is taken into account.

PMID- 18337200
TI  - Identification of differentially expressed genes in mandibular condylar and
      tibial growth cartilages using laser microdissection and fluorescent differential
      display: chondromodulin-I (ChM-1) and tenomodulin (TeM) are differentially
      expressed in mandibular condylar and other growth cartilages.
AB  - Mandibular condylar cartilage can be distinguished from articular and growth
      cartilages of long bones based on several differences in morphology, physiology,
      and function between these structures. However, there is almost no information
      available on the types of genes that contribute to these differences. In this
      study, genes that were differentially expressed in mandibular condylar and growth
      cartilages in 1-week-old rats were investigated using fluorescent differential
      display (FDD) and laser microdissection (LMD). A number of genes were identified
      by FDD including chondromodulin-1 (ChM-1), which is known to be an angiogenesis
      inhibitor of endochondral ossification. ChM-1 expression was then compared with
      that of tenomodulin (TeM) in mandibular condylar and tibial cartilages of 1- and
      5-week-old rats using real time PCR (RT-PCR), immunohistochemistry, and in situ
      hybridization. There was negligible detection of ChM-1 mRNA and protein in
      mandibular condylar cartilages compared to tibial cartilages of 1- and 5-week-old
      rats. On the other hand, TeM mRNA was more abundant in mandibular condylar
      cartilage than in tibial. These observations demonstrated that gene expression in
      mandibular condylar cartilage differed from other types of cartilage such as
      articular and growth ones.

PMID- 18337201
TI  - Sex-specific developmental changes in muscle size and bone geometry at the
      femoral shaft.
AB  - INTRODUCTION: When expressed as a percentage of the average result in young
      adults, bone mineral content lags behind bone length before puberty. Even though
      this observation has led to speculation about bone fragility in children, such
      relationships could simply be due to scaling effects when measures with different
      geometrical dimensions are compared. METHODS: The study population comprised 145
      healthy subjects (6-25 years, 94 females). Magnetic resonance imaging and dual
      energy X-ray absorptiometry were used to determine femur length, bone mineral
      content, cortical bone mineral density, cross-sectional bone geometry (bone
      diameter; cortical thickness; total, cortical and medullary areas; cross
      sectional and polar moments of area; bone strength index) and muscle area at the
      proximal one-third site of the femur. Results were dimensionally scaled by
      raising two-, three- and four-dimensional variables to the power of 1/2, 1/3 and
      1/4, respectively. Sex-differences were also assessed before and after
      functionally adjusting variables for femur length and weight or muscle size.
      RESULTS: In prepubertal children, unscaled results expressed as percentages of
      adult values were lowest for variables with the highest dimensions (e.g., moments
      of area<bone mineral content<cross-sectional areas<femur length). However, when
      dimensionally scaled, results in children represented similar percentages of the
      respective average adult values, even after functional adjustments. Before
      puberty, there was no sex-difference in adjusted bone or muscle variables. After
      puberty, males had greater total and cortical bone area, bone diameter, moments
      of area, bone strength index and muscle area than women, both in absolute terms
      as well as adjusted for femur length and weight. The largest sex-difference was
      found for muscle area. When compared relative to muscle size, young adult women
      attained greater total and cortical bone area than men. CONCLUSIONS: Growth in
      femoral length, diameter, mass and strength appears well coordinated before
      puberty. Postpubertal females have narrower femora, less bone strength and muscle
      size than males. However, when muscle size is taken into account, females have a
      larger femoral bone cross-section and more cortical bone. These sex-differences
      likely result from a combination of mechanical and hormonal effects occurring
      during puberty.

PMID- 18337203
TI  - Debates and comments.

PMID- 18337202
TI  - Comparison of the effects of genistein and zoledronic acid on the bone loss in
      OPG-deficient mice.
AB  - Using osteoprotegerin (OPG)-knockout mice, we demonstrated that in vivo the
      effects of both genistein and 17beta-estradiol (E2) on bone metabolism were
      completely abolished. In contrast, zoledronic acid could effectively suppress
      bone resorption and prevent bone loss. INTRODUCTION: The anti-resorptive effects
      of E2 on bone metabolism are considered to be mediated via modulation of the
      osteoblast-derived paracrine factor OPG. Recently, the phytoestrogen genistein
      was found to suppress bone resorption by enhancing osteoblastic production of
      OPG. However, the mechanism underlying the in vivo effects of E2 and genistein on
      bone is not entirely understood, and a central question in this regard is whether
      E2 regulates bone metabolism via an OPG-dependent pathway. METHODS: After mating
      heterozygous (OPG+/-) mice, homozygous (OPG-/-) and wild-type (WT) with a mixed
      C57BL/6J x 129/SV background were obtained. The study involved 6-week-old female
      OPG-/- (n=40) and WT mice (n=8). The OPG-/- mice were randomly divided into 5
      groups (n=8 per group) as follows: (1) genistein-treated mice (Gen) that were
      subcutaneously injected with genistein at a maximal dose (0.8 mg/day); (2) E2
      treated mice (E2) that were subcutaneously injected with E2 at a dose (0.03
      microg/day); (3) DMSO control mice (DMSO) that were subcutaneously injected with
      a mixture of dimethylsulfoxide (DMSO) and polyethyleneglycol-300; (4) zoledronic
      acid-treated mice (Zol) that were subcutaneously injected with zoledronic acid at
      a dose of (150 microg/kg) twice per week; and (5) H2O control mice that were
      subcutaneously injected with sterilized water twice per week. The doses of
      genistein, estrogen and zoledronic acid were selected based on the results of
      dose-response effect of agents on bone versus uterus in OPG-/- mice. The mice
      were sacrificed 6 weeks after this intervention. The microarchitecture of the
      trabecular and cortical bone was assessed by performing microcomputed tomography
      (micro-CT) for the right proximal tibia. The bone mineral density (BMD) of the
      left femur was measured by dual-energy X-ray absorptiometry (DXA). The
      biomechanical parameters of the right femur were determined by a three-point bend
      testing. Serum levels of bone alkaline phosphatase (B-ALP), tartarate-resistant
      acid phosphatase-5b (TRACP-5b), and receptor activator of nuclear factor kappaB
      ligand (RANKL) were determined by performing ELISA. RESULTS: DXA analysis
      revealed that the total BMD of the femur was not significantly altered in the
      Gen, E2, H2O, and DMSO groups. The three-point bending test revealed no
      significant differences in the biomechanical parameters, including ultimate
      loading, ultimate stress, stiff index, and elastic modulus, and micro-CT analysis
      revealed that the microarchitectural parameters of the trabecular bone (vBMD,
      tBMD, BVF, BSF, SMI, Tb.N, Conn.D, Tb.Sp, and Tb.Th) and cortical bone (Ct.Th,
      Mm, In.Pm, Ot.Pm, Ma.Ar, Ct.Ar, Tt.Ar, Ct.BMD, and Ct.BMC) did not differ among
      the groups. Genistein and E2 treatment did not alter the serum TRACP-5b, B-ALP,
      or RANKL levels. However, in addition to increasing the bone mass, zoledronic
      acid could effectively improve biomechanical parameters and could completely
      prevent deterioration of the bone architecture in the OPG-/- mice. CONCLUSIONS:
      The effects of genistein and E2 on bone metabolism in vivo were lost completely
      in OPG-deficient mice, suggesting that the effect of these agents on bone
      metabolism seems to be entirely dependent on OPG. In contrast, zoledronic acid
      could effectively suppress bone resorption and completely prevent the bone loss
      in the OPG-/- mice--an effect that is likely to be independent of the OPG
      pathway.

PMID- 18337204
TI  - Screening for antidepressant, sedative and analgesic activities of novel fused
      thiophene derivatives.
AB  - This study was aimed at the synthesis of fused benzothiophene derivatives
      containing heterocyclic moiety. The reaction of the tetrahydrobenzo[b]thiophene
      derivatives 1a,b with ethoxycarbonylisothiocyanate afforded the thiourea
      derivatives 2a,b. Cyclization of the latter products gave the annulated
      benzo[b]thienopyrimidine derivatives 3a,b. Compounds 2a,b and 3a underwent a
      series of heterocyclization reactions through the reaction with some chemical
      reagents to give the new benzo[b]thienopyrimidine derivatives 5a,b to 8a-c. Also,
      this work was extended to study the potential role of the novel synthesized
      thiourea derivative 2a and benzo[b]thienopyrimidine derivatives 3a, 5b, 6a and 8b
      as antidepressant, sedative or analgesic agents at two doses (15 or 30 mg kg(-1)
      body mass). Some compounds (2a, 3a and 5b) showed mild antidepressant activity in
      the forced-swimming test. No compound showed sedative effect. Visceral pain
      evoked by i.p. injection of acetic acid in mice was significantly inhibited by
      all compounds at a high doses.

PMID- 18337205
TI  - Synthesis and pharmacological activities of some condensed 4-chloro-2,2-dialkyl
      chromene-3-carbaldehyde derivatives.
AB  - Some new hydrazono 5a,b, thiosemicarbazono 6a-c, and oximo chromenes 7a-c were
      prepared via the reaction of the corresponding beta-chlorocarbaldehyde 3 with
      hydrazine, aromatic hydrazine, thiosemicarbazide and hydroxylamine hydrochloride,
      respectively. In addition, ether derivatives 8a-h were prepared from the
      corresponding aldoximes 7a-c. The new products were tested for anti-inflammatory
      and ulcerogenic score activities compared to indomethacin.

PMID- 18337206
TI  - Synthesis of progesterone heterocyclic derivatives of potential antimicrobial
      activity.
AB  - The aim of this work was to synthesize steroidal heterocycles and to elucidate
      the potential role of these compounds as antimicrobial agents. The synthesis of
      steroidal heterocycles containing the pyrazole, isoxazole, thiazole, pyrane,
      pyridine, pyridazine, or benzopyrane ring attached to the pregnene nucleus is
      reported. Progesterone (1) reacts with dimethyl formamide dimethyl acetal to form
      enamine 2. Heterocyclization of 2 with hydrazines, hydroxylamine, glycine, ethyl
      acetoacetate or cyanomethylene afforded novel steroidal heterocyclic derivatives.
      The in vitro antimicrobial evaluation showed that all synthesized compounds show
      activity against the used strains of Gram positive bacteria and fungi.

PMID- 18337207
TI  - New steroidal derivatives synthesized using 3beta-hydroxyandrosten-17-one as
      starting material.
AB  - In this study, we synthesized some new substituted steroidal derivatives using
      3beta-hydroxyandrosten-17-one (dehydroepiandrosterone) as starting material. The
      synthesized steroidal derivatives 1-11 were evaluated for their androgenic
      anabolic activities compared to testosterone as positive control. Details of the
      synthesis, spectroscopic data and toxicity (LD50) of synthesized compounds are
      reported.

PMID- 18337208
TI  - Mannan-coated gelatin nanoparticles for sustained and targeted delivery of
      didanosine: in vitro and in vivo evaluation.
AB  - Macrophages of the reticuloendothelial system and brain act as major reservoir
      for HIV because of their long term survival after HIV infection and ability to
      spread virus particles to bystander CD4 positive lymphocyte cells. The objective
      of the present study was to investigate mannan-coated nanoparticles for
      macrophage targeting of didanosine. Different didanosine loaded nanoparticles
      were prepared using the double desolvation technique and were characterized in
      vitro, ex vivo and in vivo. Results of the ex vivo cellular uptake study
      indicated 5-fold higher uptake of didanosine from the mannan-coated nanoparticles
      formulation (62.5 +/- 5.4%) by the macrophages in comparison with didanosine
      solution in phosphate buffer saline (PBS, pH 7.4) (12.1 +/- 2.3%). The better
      cellular uptake from the nanoparticles formulation was further confirmed by
      fluorescence microscopy using hydrophilic 6-carboxyfluorescein as a marker.
      Results of the quantitative biodistribution study showed 1.7, 12.6 and 12.4 times
      higher localization of didanosine in the spleen, lymph nodes and brain,
      respectively, after administration of mannan-coated nanoparticles compared to
      that after injection of didanosine solution in PBS (pH 7.4). Results of the
      present study showed that the mannan-coated nanoparticles targeted didanosine to
      the macrophage by mannosyl receptor mediated endocytosis.

PMID- 18337209
TI  - Effect of core and surface cross-linking on the entrapment of metronidazole in
      pectin beads.
AB  - The purpose of this study was to improve the entrapment efficiency of the water
      soluble drug metronidazole using internal cross-linking agents. Calcium pectinate
      beads containing metronidazole were prepared by dropping a drug-pectin solution
      in 1% and 5% (m/V) calcium chloride for surface cross-linked beads. For the core
      cross-linked beads calcium carbonate was dispersed in the drug-pectin solution.
      The beads were characterized by particle size, swelling ratio, SEM, DSC, and in
      vitro drug release. It was found that the beads obtained by core cross-linking
      produced more drug entrapped beads than the surface cross-linked beads. Beads
      obtained using 1% (m/V) calcium chloride showed more drug entrapment than these
      obtained using 5% calcium chloride. The core cross-linking of pectin beads
      reduced drug loss by about 10-20%. The water lodging capacity of beads depended
      upon gel strength which is a function of the internal gelling agent and pectin
      concentration. Complete drug release was observed within 30-60 min in the acidic
      dissolution medium. This work has showed that the core cross-linking agent
      increases the water-soluble drug entrapment in calcium pectinate beads.

PMID- 18337210
TI  - A sensitive spectrophotometric method for the determination of H2-receptor
      antagonists by means of N-bromosuccinimide and p-aminophenol.
AB  - A simple, accurate and sensitive spectrophotometric method for determination of
      H2-receptor antagonists: cimetidine (CIM), famotidine (FAM), nizatidine (NIZ),
      and ranitidine hydrochloride (RAN) has been fully developed and validated. The
      method was based on the reaction of these drugs with NBS and subsequent
      measurement of the excess N-bromosuccinimide by its reaction with p-aminophenol
      to give a violet colored product (lambda max at 552 nm). Decrease in the
      absorption intensity (Delta A) of the colored product, due to the presence of the
      drug, was correlated with its concentration in the sample solution. Different
      variables affecting the reaction were carefully studied and optimized. Under
      optimal conditions, linear relationships with good correlation coefficients
      (0.9988-0.9998) were found between Delta A values and the corresponding
      concentrations of the drugs in a concentration range of 8-30, 6-22, 6-25, and 4
      20 microg mL(-1) for CIM, FAM, NIZ, and RAN, respectively. Limits of detection
      were 1.22, 1.01, 1.08, and 0.74 microg mL(-1) for CIM, FAM, NIZ, and RAN,
      respectively. The method was validated in terms of accuracy, precision,
      ruggedness, and robustness; the results were satisfactory. The proposed method
      was successfully applied to the analysis of the above mentioned drugs in bulk
      substance and in pharmaceutical dosage forms; percent recoveries ranged from 98.5
      +/- 0.9 to 102.4 +/- 0.8% without interference from the common excipients. The
      results obtained by the proposed method were comparable with those obtained by
      the official methods.

PMID- 18337211
TI  - Solid dispersion of meloxicam: factorially designed dosage form for geriatric
      population.
AB  - The objective of the present work was to improve the dissolution properties of
      the poorly water-soluble drug meloxicam by preparing solid dispersions with
      hydroxyethyl cellulose (HEC), mannitol and polyethylene glycol (PEG) 4000 and to
      develop a dosage form for geriatric population. Differential scanning
      calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy and
      scanning electron microscopy were used to investigate the solid-state physical
      structure of the prepared solid dispersions. Higher in vitro dissolution of solid
      dispersions was recorded compared to their corresponding physical mixtures and
      the pure drug. PEG 4000 in 1: 9 drug to carrier ratio exhibited the highest drug
      release (100.2%), followed by mannitol (98.2%) and HEC (89.5%) in the same ratio.
      Meloxicam-PEG 4000 solid dispersion was formulated into suspension and
      optimization was carried out by 23 factorial design. Formulations containing
      higher levels of methyl cellulose and higher levels of either sodium citrate or
      Tween 80 exhibited the highest drug release.

PMID- 18337212
TI  - Use of Folin-Ciocalteu phenol reagent and 3-methyl-2-benzothiazolinone hydrazine
      hydrochloride in the determination of oxcarbazepine in pharmaceuticals.
AB  - Two spectrophotometric methods are proposed for the assay of oxcarbazepine (OXC)
      in bulk and dosage forms using Folin-Ciocalteu phenol reagent (FCP) and 3-methyl
      2-benzothiazolinone hydrazine hydrochloride (MBTH) as reagents. The first method
      involves addition of FCP reagent to OXC in alkaline medium followed by
      measurement of absorbance at 760 nm (method A), and the other involves addition
      of a fixed volume of MBTH after treatment of OXC with ferric chloride and
      measurement of absorbance at 456 nm (method B). In both methods, the amount of
      chromogen formed corresponds to the amount of OXC and the measured absorbance was
      found to increase linearly with the concentration of OXC, which is corroborated
      by the correlation coefficients of 0.9985 and 0.9984 for method A and B,
      respectively. The systems obey Beer's law for 5-30 microg mL(-1) and 10-50 microg
      mL(-1) for methods A and B, respectively. The apparent molar absorptivity was
      calculated to be 8.06 x 10(3) L mol(-1) cm(-1) and 3.126 x 10(3) L mol(-1) cm(-1)
      for methods A and B, respectively. The limits of detection (LOD) and limit of
      quantification (LOQ) were calculated to be 1.6 and 5 microg mL(-1) for method A
      and 3 and 10 microg mL(-1) for method B. The inter-day and intra-day imprecision
      of the methods were found to be in the range of 1.1-1.7 and 0.9-1.1% for method
      A, and 1.1-1.9 and 0.6-0.9% for method B. The accuracy ranged between 98.9-99.7%
      and 99.3-100.1 for method A and B, respectively. No interference was observed
      from common pharmaceutical excipients. The methods were successfully applied to
      the assay of OXC in tablet preparations.

PMID- 18337213
TI  - Synthesis and evaluation of the biological activities of some 3-{[5-(6-methyl-4
      aryl-2-oxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3
      dihydro-2H-indol-2-one derivatives.
AB  - Reaction of ethyl-6-methyl-2-oxo-4-aryl-1,2,3,4-tetrahydropyrimidin-5
      carboxylates (1a-i) with hydrazine hydrate yielded 6-methyl-2-oxo-4-aryl-1,2,3,4
      tetrahydropyrimidin-5-carbohydrazides (2a-i). These products, on reaction with
      cyanogen bromide, gave 5-(5-amino-1,3,4-oxadiazol-2-yl)-6-methyl-4-aryl-3,4
      dihydropyrimidin-2 (1H)-ones (3a-i). The resultant aminooxadiazolylpyrimidinones
      were condensed with isatin to obtain various 3-{[5-(6-methyl-4-aryl-2-oxo-1,2,3,4
      tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl]-imino}-1,3-dihydro-2H-indol-2
      ones (4a-i). These products were characterized by IR, 1H NMR, mass spectra and
      elemental analysis. Products (4a-i) revealed promising antibacterial, antifungal
      and antioxidant activity.

PMID- 18337214
TI  - Simple learning rules to cope with changing environments.
AB  - We consider an agent that must choose repeatedly among several actions. Each
      action has a certain probability of giving the agent an energy reward, and costs
      may be associated with switching between actions. The agent does not know which
      action has the highest reward probability, and the probabilities change randomly
      over time. We study two learning rules that have been widely used to model
      decision-making processes in animals-one deterministic and the other stochastic.
      In particular, we examine the influence of the rules' 'learning rate' on the
      agent's energy gain. We compare the performance of each rule with the best
      performance attainable when the agent has either full knowledge or no knowledge
      of the environment. Over relatively short periods of time, both rules are
      successful in enabling agents to exploit their environment. Moreover, under a
      range of effective learning rates, both rules are equivalent, and can be
      expressed by a third rule that requires the agent to select the action for which
      the current run of unsuccessful trials is shortest. However, the performance of
      both rules is relatively poor over longer periods of time, and under most
      circumstances no better than the performance an agent could achieve without
      knowledge of the environment. We propose a simple extension to the original rules
      that enables agents to learn about and effectively exploit a changing environment
      for an unlimited period of time.

PMID- 18337217
TI  - Drug delivery systems.

PMID- 18337218
TI  - Liposomal nanomedicines: an emerging field.
AB  - Liposomal nanoparticles (LNs) encapsulating therapeutic agents, or liposomal
      nanomedicines (LNMs), represent one of the most advanced classes of drug delivery
      systems, with several currently on the market and many more in clinical trials.
      During the past 20 years, a variety of techniques have been developed for
      encapsulating both conventional drugs and the new genetic drugs (plasmid DNA
      containing therapeutic genes, antisense oligonucleotides, and small, interfering
      RNA [siRNA]) within LNs encompassing a very specific set of properties: a
      diameter centered on 100 nm, a high drug-to-lipid ratio, excellent retention of
      the encapsulated drug, and a long (>6 hours) circulation lifetime. Particles with
      these properties tend to accumulate at sites of disease, such as tumors, where
      the endothelial layer is "leaky" and allows extravasation of particles with small
      diameters. Thus, LNs protect the drug during circulation, prevent it from
      reaching healthy tissues, and permit its accumulation at sites of disease. We
      will discuss recent advances in this field involving conventional anticancer
      drugs as well as gene-delivery, immunostimulatory, and gene-silencing
      applications involving the new genetic drugs. LNMs have the potential to offer
      new treatments in such areas as cancer therapy, vaccine development, and
      cholesterol management.

PMID- 18337219
TI  - Cyclodextrins.
AB  - beta-cyclodextrin (beta-CD) and other cyclodextrins (CDs) have utility for
      solubilizing and stabilizing drugs; however, some are nephrotoxic when
      administered parenterally. A number of workers have attempted to identify,
      prepare, and evaluate various CD derivatives with superior inclusion complexation
      and maximal in vivo safety for various biomedical uses. A systematic study led to
      SBE-beta-CD (Captisol), a polyanionic variably substituted sulfobutyl ether of
      beta-CD, as a non-nephrotoxic derivative and HP-beta-CD, a modified CD developed
      by Janssen. SBE-beta-CD and HP-beta-CD have undergone extensive safety studies
      and are currently used in six products approved by the Food and Drug
      Administration (four for Captisol and two for HP-beta-CD). They are also in use
      in numerous clinical and preclinical studies. This article will focus on the
      issues that led to the development of these two CDs, their safety,
      characterization, and applications, and especially their ability to improve drug
      delivery. SBE-beta-CD interacts very well with neutral drugs to facilitate
      solubility and chemical stability, and because of its polyanionic nature, it
      interacts particularly well with cationic drugs. Complexes between SBE-beta-CD
      and HP-beta-CD and various drugs have been shown to rapidly dissociate after
      parenteral drug administration, to have no tissue-irritating effects after
      intramuscular dosing, and to result in superior oral bioavailability of poorly
      water-soluble drugs. The pharmacokinetics, tissue distribution, and cellular
      effects of some representative CDs, including SBE-beta-CD and HP-beta-CD, are
      reviewed. The safety profiles of CDs are discussed, with emphasis on the
      biological effects of some CDs on the gastrointestinal tract, kidney, and
      reproduction and development and the carcinogenic potential of CDs. In addition,
      human experience with CD derivatives, specifically SBE-beta-CD and HP-beta-CD,
      indicates that these two CDs are well tolerated in humans and have no adverse
      effects on the kidneys or other organs following either oral or intravenous
      administration.

PMID- 18337220
TI  - Drug nanoparticles: formulating poorly water-soluble compounds.
AB  - More than 40% of compounds identified through combinatorial screening programs
      are poorly soluble in water. These molecules are difficult to formulate using
      conventional approaches and are associated with innumerable formulation-related
      performance issues. Formulating these compounds as pure drug nanoparticles is one
      of the newer drug-delivery strategies applied to this class of molecules.
      Nanoparticle dispersions are stable and have a mean diameter of less than 1
      micron. The formulations consist of water, drug, and one or more generally
      regarded as safe excipients. These liquid dispersions exhibit an acceptable shelf
      life and can be postprocessed into various types of solid dosage forms. Drug
      nanoparticles have been shown to improve bioavailability and enhance drug
      exposure for oral and parenteral dosage forms. Suitable formulations for the most
      commonly used routes of administration can be identified with milligram
      quantities of drug substance, providing the discovery scientist with an alternate
      avenue for screening and identifying superior analogs. For the toxicologist, the
      approach provides a means for dose escalation using a formulation that is
      commercially viable. In the past few years, formulating poorly water-soluble
      compounds using a nanoparticulate approach has evolved from a conception to a
      realization whose versatility and applicability are just beginning to be
      realized.

PMID- 18337221
TI  - Safety evaluation of ocular drug delivery formulations: techniques and practical
      considerations.
AB  - Development of new drug candidates and novel delivery techniques for treatment of
      ocular diseases has recently accelerated. Treatment of anterior-segment diseases
      has witnessed advances in prodrug formulations and permeability enhancers.
      Intravitreal, subconjunctival, and periocular routes of administration and
      sustained-release formulations of nanoparticles and microparticles, as well as
      nonbiodegradable and biodegradable implants to deliver drugs to the posterior
      segment of the eye, are becoming popular therapeutic approaches. Without adequate
      regulatory guidance for ocular drugs, such routes of administration and novel
      formulations can pose unique challenges to those involved in designing
      nonclinical programs, including considering clinical and nonclinical factors and
      choosing species, strains, and ocular toxicity parameters. Toxicologic
      pathologists also contribute practical experience to evaluating morphological
      effects of these novel formulations. Lastly, understanding species' anatomical
      differences is useful for interpreting toxicological and pathological responses
      to the eye and is important for human risk assessment of these important new
      therapies for ocular diseases.

PMID- 18337222
TI  - Medical device regulations and testing for toxicologic pathologists.
AB  - Awareness of the regulatory environment is fundamental to understanding the
      biological assessment of biomaterials and medical devices. Medical devices are a
      diverse and heterogeneous group of medical products and technologies defined by
      the lack of chemical action or requirement for metabolism. Regional activity and
      the Global Harmonization Task Force are now working on harmonizing the
      categorization and testing of medical devices. The International Organization for
      Standardization (ISO) has published 19 standards for biological evaluation. ISO
      10993 standards are generally accepted outright or as an alternative to most
      national regulatory directives or acts, although Japan and the United States
      require more stringency in some tests. Type of materials, intended use, and risk
      are the basis for drafting testing programs for biomaterials and medical devices.
      With growth of the medical device industry and advent of new biomaterials and
      technologies, the need for toxicologic pathologists in safety (biocompatibility)
      and efficacy (conditions of use) evaluation of moderate- to high-risk devices is
      expanding. Preclinical evaluation of biomaterials and medical devices
      increasingly requires a basic understanding of materials science and
      bioengineering to facilitate interpretation of complex interface reactions
      between biomaterials, cellular and secretory factors, and vascular and tissue
      responses that modulate success or failure of medical devices.

PMID- 18337223
TI  - Biocompatibility: meeting a key functional requirement of next-generation medical
      devices.
AB  - The array of polymeric, biologic, metallic, and ceramic biomaterials will be
      reviewed with respect to their biocompatibility, which has traditionally been
      viewed as a requirement to develop a safe medical device. With the emergence of
      combination products, a paradigm shift is occurring that now requires
      biocompatibility to be designed into the device. In fact, next-generation medical
      devices will require enhanced biocompatibility by using, for example,
      pharmacological agents, bioactive coatings, nano-textures, or hybrid systems
      containing cells that control biologic interactions to have desirable biologic
      outcomes. The concept of biocompatibility is moving from a "do no harm" mission
      (i.e., nontoxic, nonantigenic, nonmutagenic, etc.) to one of doing "good," that
      is, encouraging positive healing responses. These new devices will promote the
      formation of normal healthy tissue as well as the integration of the device into
      adjacent tissue. In some contexts, biocompatibility can become a disruptive
      technology that can change therapeutic paradigms (e.g., drug-coated stents). New
      database tools to access biocompatibility data of the materials of construction
      in existing medical devices will facilitate the use of existing and new
      biomaterials for new medical device designs.

PMID- 18337224
TI  - Preparation of medical devices for evaluation.
AB  - Preparing and processing medical device implants for evaluation is a relatively
      high-risk and high-dollar process in which studies get made and endpoints can be
      lost with no second chance. It is important to customize every aspect of the
      preparation process to the type of device and the study endpoints. Some standard
      and proven approaches for a few types of implants are discussed, addressing
      fixation, special dissection and extraction techniques, preprocessing imaging,
      trimming techniques, sample processing, embedding media, and cutting and staining
      options.

PMID- 18337225
TI  - Medical devices in orthopedic applications.
AB  - Orthopedic medical devices have been extremely successful in restoring mobility,
      reducing pain, and improving the quality of life for millions of individuals each
      year. Their success is reflected in the worldwide biomaterials market, in which
      orthopedic devices dominated sales at approximately $14 billion in 2002. Of this,
      approximately $12 billion was spent on joint replacements. In spite of their
      overwhelming benefits and successes, orthopedic medical devices are not without
      risk of adverse effects. Most adverse joint replacement outcomes are thought to
      be mediated by degradation products generated by wear and electrochemical
      corrosion. Infection and flaws in device manufacturing are other noteworthy
      causes of orthopedic device failure. This article illustrates and discusses the
      uses, general properties, and limitations (including adverse outcomes) of
      orthopedic biomaterials, which are fundamental to understanding requirements for
      improving current orthopedic medical devices.

PMID- 18337226
TI  - Tissue engineering and regenerative medicine: role of toxicologic pathologists
      for an emerging medical technology.
AB  - Tissue Engineering Regenerative Medical (TERM) products are a new technology
      currently in human clinical testing for a variety of unmet medical needs
      involving tissue and organ dysfunction and failure. Safety evaluation of TERM
      products overlaps 3 established product paradigms: pharmaceuticals (biologically
      active substances), transplantation (cells or tissue), and devices
      (biomaterials). As TERM products recapitulate organ or tissue structure and
      function with unique biological activity and characteristics, they require new
      preclinical paradigms to bring TERM products through to clinical trials.
      Establishing TERM-product safety programs requires broad-based knowledge of
      tissue and organ homeostasis, regenerative biology, and translational medicine to
      design new preclinical paradigms. Therefore, toxicologic pathologists have a
      compelling scientific role in evaluating TERM products, characterizing tissue
      responses, and helping distinguish optimal (regeneration) from deficient or
      incomplete outcomes indicative of substandard functionality (repair). As new
      tissue engineering and regenerative medical technologies develop for tissue and
      organ regeneration, the toxicologic pathologist will be asked to develop novel
      testing, reevaluate established toxicologic diagnostic criteria, and reinterpret
      tissue responses that may extend beyond current standards.

PMID- 18337227
TI  - Gene therapy: some history, applications, problems, and prospects.
AB  - The concept of transferring genes to tissues for clinical applications has been
      discussed for nearly half a century, but our ability to manipulate genetic
      material via recombinant DNA technology has brought this goal to reality. While
      originally conceived as a way to treat life-threatening disorders (inborn errors,
      cancers) refractory to conventional treatment, gene therapy now is considered for
      many non-life-threatening conditions, including those adversely affecting a
      patient's quality of life. The lack of suitable treatment has become a rational
      basis for extending the scope of gene therapy. This manuscript reviews the
      general methods by which genes are transferred as well as diverse examples of
      clinical applications (acquired tissue damage, upper gastrointestinal tract
      infection, autoimmune disease, systemic protein deficiency). Despite some well
      publicized problems, gene therapy has made substantive progress, including
      tangible success, albeit much slower than was initially predicted. Although gene
      therapy is still at a fairly primitive stage, it is firmly science based. There
      is justifiable optimism that with increased pathobiological understanding and
      biotechnological improvements, gene therapy will become a standard part of
      clinical practice within 20 years.

PMID- 18337228
TI  - An approach to achieve long-term expression in skin gene therapy.
AB  - For gene therapy purposes, the skin is an attractive organ to target for systemic
      delivery of therapeutic proteins to treat systemic diseases, skin diseases, or
      skin cancer. To achieve long-term stable expression of a therapeutic gene in
      keratinocytes (KC), we have developed an approach using a bicistronic retroviral
      vector expressing the desired therapeutic gene linked to a selectable marker
      (multidrug resistant gene, MDR) that is then introduced into KC and fibroblasts
      (FB) to create genetically modified human skin equivalent (HSE). After grafting
      the HSE onto immunocompromised mice, topical colchicine treatment is used to
      select and enrich for genetically modified keratinocyte stem cells (KSC) that
      express MDR and are resistant to colchicine's antimitotic effects. Both the
      apparatus for topical colchicine delivery and the colchicine doses have been
      optimized for application to human skin. This approach can be validated by
      systemic delivery of therapeutic factors such as erythropoietin and the
      antihypertensive atrial natriuretic peptide.

PMID- 18337229
TI  - The application of fluorescent quantum dots to confocal, multiphoton, and
      electron microscopic imaging.
AB  - Fluorescent quantum dots are emerging as an important tool for imaging cells and
      tissues, and their unique optical and physical properties have captured the
      attention of the research community. The most common types of commercially
      available quantum dots consist of a nanocrystalline semiconductor core composed
      of cadmium selenide with a zinc sulfide capping layer and an outer polymer layer
      to facilitate conjugation to targeting biomolecules such as immunoglobulins. They
      exhibit high fluorescent quantum yields and have large absorption cross-sections,
      possess excellent photostability, and can be synthesized so that their narrow
      band fluorescence emission can occur in a wide spectrum of colors. These
      properties make them excellent candidates for serving as multiplexing molecular
      beacons using a variety of imaging modalities including highly correlated
      microscopies. Whereas much attention has been focused on quantum-dot applications
      for live-cell imaging, we have sought to characterize and exploit their utility
      for enabling simultaneous multiprotein immunolabeling in fixed cells and tissues.
      Considerations for their application to immunolabeling for correlated light and
      electron microscopic analysis are discussed.

PMID- 18337230
TI  - Applications of laser scanning cytometry in immunohistochemistry and routine
      histopathology.
AB  - Laser scanning cytometry (LSC) is a powerful tool for qualitative and
      quantitative analysis of tissue sections in preclinical drug development. LSC
      combines the strengths of flow cytometry with tissue architecture retention. This
      technology has been used predominantly with immunofluorescent techniques on cell
      culture and tissue sections, but recently LSC has shown promise in evaluating
      chromogenic immunohistochemistry (IHC) and histochemical products in paraffin
      embedded and/or frozen tissue sections. Inverted light scatter measurements or a
      combination of inverted scatter and fluorescence allows automated determination
      of cell/nuclear counts (e.g., proliferation labeling indices), cell area (e.g.,
      cellular hypertrophy), stromal elements, and labeling intensity (e.g.,
      cytoplasmic/organellar proteins) in chromogen-labeled IHC or histochemical
      stained sections that correlates well with standard manual quantification
      methods. Segmentation with autofluorescence or dual immunolabeling facilitates
      capture of labeling data from specific cell populations. LSC evaluation of HE
      stained sections is accomplished using autofluorescence/eosin fluorescence and
      inverse scatter. A standardized fluorescent approach with archivability, a lack
      of fluorescence quenching (photobleaching), and amenability to evaluation of
      multiple markers in a section has been demonstrated using Qdot nanocrystals.
      Examples of LSC use in chromogenic IHC, routine histopathology, and Qdot labeling
      will be reviewed, and advantages and disadvantages of this technology will be
      discussed.

PMID- 18337231
TI  - Pharmacodynamic monitoring of molecular-targeted agents in the peripheral blood
      of leukemia patients using flow cytometry.
AB  - The introduction of specific, molecular-targeted drugs is radically changing
      cancer treatment. Pharmacodynamics, which measures drug effects on the host, is
      key during early-phase clinical trials of novel agents to determine the relations
      between drug dose and target inhibition as well as measure the downstream effects
      of target inhibition on the cancer. In this article, we describe the application
      of flow cytometry to the pharmacodynamic monitoring of molecular-targeted agents
      in leukemia patients. The methods are based on current clinical flow-cytometry
      applications, with the addition of phosphospecific antibodies to measure the
      activation states of intracellular signaling elements and the introduction of
      techniques that maintain drug-target equilibrium during sample preparation. Using
      this approach, we successfully showed dose-dependent inhibition of c-Kit during a
      phase I clinical trial treating acute leukemia patients with the novel agent
      sorafenib. Further refinements identify considerable interpatient variation in
      signaling activity within leukemic blast populations, suggesting that an
      individualized approach to treatment based on flow cytometric monitoring might be
      advantageous. Improvements in sample turnaround offer the potential to introduce
      real-time pharmacodynamic monitoring during early-phase clinical trials.

PMID- 18337232
TI  - Metabolic profiling as a tool for understanding mechanisms of toxicity.
AB  - Metabolic profiling (metabolomics/metabonomics) is the measurement in biological
      systems of the complement of low-molecular-weight metabolites and their
      intermediates that reflects the dynamic response to genetic modification and
      physiological, pathophysiological, and/or developmental stimuli. The measurement
      and interpretation of the endogenous metabolite profile from a biological sample
      (typically urine, serum, or biological tissue extract) have provided many
      opportunities to investigate the changes induced by external stimuli (e.g., drug
      treatment) or enhance our knowledge of inherent biological variation within
      subpopulations. This article will focus on the basic principles of metabolic
      profiling and how the tools (nuclear magnetic resonance [NMR], liquid
      chromatography-mass spectrometry [LC-MS]) can be applied in toxicology and
      pathology. Metabolic profiling can complement conventional methodologies and
      other "omics" technologies in investigating preclinical drug development issues.
      Case studies will illustrate the value of metabolic profiling in improving our
      understanding of phospholipidosis and peroxisome proliferation. A key message
      will be that metabolic profiling offers huge potential to highlight biomarkers
      and mechanisms in support of toxicology and pathology investigations in
      preclinical drug development.

PMID- 18337234
TI  - Prostaglandin F2-alpha receptor regulation in human uterine myocytes.
AB  - Investigations of the modulation of prostaglandin F(2alpha) receptor (FP)
      expression in primary cultures of human uterine myocytes showed that FP mRNA
      expression was reduced by progesterone, unaltered by cAMP (8-bromo cAMP or
      forskolin), but increased by the PKA antagonist H89. Interleukin (IL)-1beta,
      tumour necrosis factor-alpha and oxytocin increased FP mRNA expression and IL-6
      and prostaglandin E(2) reduced FP mRNA expression. The changes in FP protein
      levels were similar to the mRNA responses. We found that the IL-1beta-induced
      increase in FP expression was mediated at least in part via protein kinase C
      (PKC), but was independent of mitogen-activated protein kinase, phospholipase C
      and PI3 kinase. Since IL-1beta activates NFkappaB, AP-1 and C/EBP, we over
      expressed these transcription factors alone and in combination and found that
      only NFkappaB alone increased FP mRNA expression. Finally, we found that the IL
      1beta-induced increase in FP expression was unaffected by progesterone and/or
      cAMP, but was accentuated by H89. These data suggest that the pregnancy-induced
      down-regulation in myometrial FP expression is mediated by progesterone and cAMP
      and that the increase with labour is induced by inflammatory cytokine activation
      of PKC and NFkappaB.

PMID- 18337235
TI  - Comprehensive cardiovascular magnetic resonance for diagnosis of cardiac hydatid
      cyst.

PMID- 18337236
TI  - Optical coherence tomography assessment of vulnerable plaque rupture:
      predilection for the plaque 'shoulder'.

PMID- 18337237
TI  - Evolving concepts of left ventricular hypertrophy.

PMID- 18337238
TI  - Asymptomatic coronary artery aneurysms: echocardiography, cardiac magnetic
      resonance, and coronariography assessment.

PMID- 18337239
TI  - Why do men and women differ in their risk of myocardial infarction?

PMID- 18337240
TI  - Hepatic overexpression of hormone-sensitive lipase and adipose triglyceride
      lipase promotes fatty acid oxidation, stimulates direct release of free fatty
      acids, and ameliorates steatosis.
AB  - Hepatic steatosis is often associated with insulin resistance and obesity and can
      lead to steatohepatitis and cirrhosis. In this study, we have demonstrated that
      hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), two
      enzymes critical for lipolysis in adipose tissues, also contribute to lipolysis
      in the liver and can mobilize hepatic triglycerides in vivo and in vitro.
      Adenoviral overexpression of HSL and/or ATGL reduced liver triglycerides by 40
      60% in both ob/ob mice and mice with high fat diet-induced obesity. However,
      these enzymes did not affect fasting plasma triglyceride and free fatty acid
      levels or triglyceride and apolipoprotein B secretion rates. Plasma 3-beta
      hydroxybutyrate levels were increased 3-5 days after infection in both HSL- and
      ATGL-overexpressing male mice, suggesting an increase in beta-oxidation.
      Expression of genes involved in fatty acid transport and synthesis, lipid
      storage, and mitochondrial bioenergetics was unchanged. Mechanistic studies in
      oleate-supplemented McA-RH7777 cells with adenoviral overexpression of HSL or
      ATGL showed that reduced cellular triglycerides could be attributed to increases
      in beta-oxidation as well as direct release of free fatty acids into the medium.
      In summary, hepatic overexpression of HSL or ATGL can promote fatty acid
      oxidation, stimulate direct release of free fatty acid, and ameliorate hepatic
      steatosis. This study suggests a direct functional role for both HSL and ATGL in
      hepatic lipid homeostasis and identifies these enzymes as potential therapeutic
      targets for ameliorating hepatic steatosis associated with insulin resistance and
      obesity.

PMID- 18337241
TI  - Novel role for STIM1 as a trigger for calcium influx factor production.
AB  - STIM1 has been recently identified as a Ca(2+) sensor in endoplasmic reticulum
      (ER) and an initiator of the store-operated Ca(2+) entry (SOCE) pathway, but the
      mechanism of SOCE activation remains controversial. Here we focus on the early ER
      delimited steps of the SOCE pathway and demonstrate that STIM1 is critically
      involved in initiating of production of calcium influx factor (CIF), a diffusible
      messenger that can deliver the signal from the stores to plasma membrane and
      activate SOCE. We discovered that CIF production is tightly coupled with STIM1
      expression and requires functional integrity of its intraluminal sterile alpha
      motif (SAM) domain. We demonstrate that 1) molecular knockdown or overexpression
      of STIM1 results in corresponding impairment or amplification of CIF production
      and 2) inherent deficiency in the ER-delimited CIF production and SOCE activation
      in some cell types can be a result of their deficiency in STIM1 protein;
      expression of a wild-type STIM1 in such cells was sufficient to fully rescue
      their ability to produce CIF and SOCE. We found that glycosylation sites in the
      ER-resident SAM domain of STIM1 are essential for initiation of CIF production.
      We propose that after STIM1 loses Ca(2+) from EF hand, its intraluminal SAM
      domain may change conformation, and via glycosylation sites it can interact with
      and activate CIF-producing machinery. Thus, CIF production appears to be one of
      the earliest STIM1-dependent events in the ER lumen, and impairment of this
      process results in impaired SOCE response.

PMID- 18337242
TI  - The cytoplasmic loops of subunit a of Escherichia coli ATP synthase may
      participate in the proton translocating mechanism.
AB  - Subunit a plays a key role in promoting H(+) transport and the coupled rotary
      motion of the subunit c ring in F(1)F(0)-ATP synthase. H(+) binding and release
      occur at Asp-61 in the middle of the second transmembrane helix (TMH) of F(0)
      subunit c. H(+) are thought to reach Asp-61 via aqueous pathways mapping to the
      surfaces of TMHs 2-5 of subunit a based upon the chemical reactivity of Cys
      substituted into these helices. Here we substituted Cys into loops connecting
      TMHs 1 and 2 (loop 1-2) and TMHs 3 and 4 (loop 3-4). A large segment of loop 3-4
      extending from loop residue 192 loop to residue 203 in TMH4 at the lipid bilayer
      surface proved to be very sensitive to inhibition by Ag(+). Cys-161 and -165 at
      the other end of the loop bordering TMH3 were also sensitive to inhibition by
      Ag(+). Further Cys substitutions in residues 86 and 93 in the middle of the 1-2
      loop proved to be Ag(+)-sensitive. We next asked whether the regions of Ag(+)
      sensitive residues clustered together near the surface of the membrane by
      combining Cys substitutions from two domains and testing for cross-linking. Cys
      161 and -165 in loop 3-4 were found to cross-link with Cys-202, -203, or -205,
      which extend into TMH4 from the cytoplasm. Further Cys at residues 86 and 93 in
      loop 1-2 were found to cross-link with Cys-195 in loop 3-4. We conclude that the
      Ag(+)-sensitive regions of loops 1-2 and 3-4 may pack in a single domain that
      packs at the ends of TMHs 3 and 4. We suggest that the Ag(+)-sensitive domain may
      be involved in gating H(+) release at the cytoplasmic side of the aqueous access
      channel extending through F(0).

PMID- 18337243
TI  - Sequential protein kinase C (PKC)-dependent and PKC-independent protein kinase D
      catalytic activation via Gq-coupled receptors: differential regulation of
      activation loop Ser(744) and Ser(748) phosphorylation.
AB  - Protein kinase D (PKD) is a serine/threonine protein kinase rapidly activated by
      G protein-coupled receptor (GPCR) agonists via a protein kinase C (PKC)-dependent
      pathway. Recently, PKD has been implicated in the regulation of long term
      cellular activities, but little is known about the mechanism(s) of sustained PKD
      activation. Here, we show that cell treatment with the preferential PKC
      inhibitors GF 109203X or Go 6983 blocked rapid (1-5-min) PKD activation induced
      by bombesin stimulation, but this inhibition was greatly diminished at later
      times of bombesin stimulation (e.g. 45 min). These results imply that GPCR
      induced PKD activation is mediated by early PKC-dependent and late PKC
      independent mechanisms. Western blot analysis with site-specific antibodies that
      detect the phosphorylated state of the activation loop residues Ser(744) and
      Ser(748) revealed striking PKC-independent phosphorylation of Ser(748) as well as
      Ser(744) phosphorylation that remained predominantly but not completely PKC
      dependent at later times of bombesin or vasopressin stimulation (20-90 min). To
      determine the mechanisms involved, we examined activation loop phosphorylation in
      a set of PKD mutants, including kinase-deficient, constitutively activated, and
      PKD forms in which the activation loop residues were substituted for alanine. Our
      results show that PKC-dependent phosphorylation of the activation loop Ser(744)
      and Ser(748) is the primary mechanism involved in early phase PKD activation,
      whereas PKD autophosphorylation on Ser(748) is a major mechanism contributing to
      the late phase of PKD activation occurring in cells stimulated by GPCR agonists.
      The present studies identify a novel mechanism induced by GPCR activation that
      leads to late, PKC-independent PKD activation.

PMID- 18337244
TI  - Restoration of susceptibility of methicillin-resistant Staphylococcus aureus to
      beta-lactam antibiotics by acidic pH: role of penicillin-binding protein PBP 2a.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is a global scourge, and
      treatment options are becoming limited. The MRSA phenotype reverts to that of
      beta-lactam-sensitive S. aureus when bacteria are grown at pH 5.0 in broth and,
      more importantly from a medical perspective (protracted, relapsing infections),
      after phagocytosis by macrophages, where the bacteria thrive in the acidic
      environment of phagolysosomes. The central factor for the MRSA phenotype is the
      function of the penicillin-binding protein (PBP) 2a, which maintains
      transpeptidase activity while being poorly inhibited by beta-lactams because of a
      closed conformation of its active site. We document herein by binding,
      acylation/deacylation kinetics, and circular dichroism spectroscopy with purified
      PBP 2a that at acidic pH (i) beta-lactams interact with PBP 2a more avidly; (ii)
      the non-covalent pre-acylation complex exhibits a lower dissociation constant and
      an increased rate of acyl-enzyme formation (first-order rate constant) without
      change in hydrolytic deacylation rate; and (iii) PBP 2a undergoes a
      conformational change in the presence of the antibiotic consistent with the
      opening of the active site from the closed conformation. These observations argue
      that PBP 2a most likely evolved for its physiological function at pH 7 or higher
      by adopting a closed conformation, which is not maintained at acidic pH. Although
      at the organism level the effect of acidic pH on other biological processes in
      MRSA could not be discounted, our report should provide the impetus for closer
      examination of the properties of PBP 2a at low pH and thereby identifying novel
      points of intervention in combating this problematic organism.

PMID- 18337245
TI  - RNF8-dependent and RNF8-independent regulation of 53BP1 in response to DNA
      damage.
AB  - The DNA damage surveillance network orchestrates cellular responses to DNA damage
      through the recruitment of DNA damage-signaling molecules to DNA damage sites and
      the concomitant activation of protein phosphorylation cascades controlled by the
      ATM (ataxia-telangiectasia-mutated) and ATR (ATM-Rad3-related) kinases.
      Activation of ATM/ATR triggers cell cycle checkpoint activation and adaptive
      responses to DNA damage. Recent studies suggest that protein ubiquitylation or
      degradation plays an important role in the DNA damage response. In this study, we
      examined the potential role of the proteasome in checkpoint activation and
      ATM/ATR signaling in response to UV light-induced DNA damage. HeLa cells treated
      with the proteasome inhibitor MG-132 showed delayed phosphorylation of ATM
      substrates in response to UV light. UV light-induced phosphorylation of 53BP1, as
      well as its recruitment to DNA damage foci, was strongly suppressed by proteasome
      inhibition, whereas the recruitment of upstream regulators of 53BP1, including
      MDC1 and H2AX, was unaffected. The ubiquitin-protein isopeptide ligase RNF8 was
      critical for 53BP1 focus targeting and phosphorylation in ionizing radiation
      damaged cells, whereas UV light-induced 53BP1 phosphorylation and targeting
      exhibited partial dependence on RNF8 and the ubiquitin-conjugating enzyme UBC13.
      Suppression of RNF8 or UBC13 also led to subtle defects in UV light-induced G2/M
      checkpoint activation. These findings are consistent with a model in which RNF8
      ubiquitylation pathways are essential for 53BP1 regulation in response to
      ionizing radiation, whereas RNF8-independent pathways contribute to 53BP1
      targeting and phosphorylation in response to UV light and potentially other forms
      of DNA replication stress.

PMID- 18337246
TI  - New insights into the mechanism of RNA degradation by ribonuclease II:
      identification of the residue responsible for setting the RNase II end product.
AB  - RNase II is a key exoribonuclease involved in the maturation, turnover, and
      quality control of RNA. RNase II homologues are components of the exosome, a
      complex of exoribonucleases. The structure of RNase II unraveled crucial aspects
      of the mechanism of RNA degradation. Here we show that mutations in highly
      conserved residues at the active site affect the activity of the enzyme.
      Moreover, we have identified the residue that is responsible for setting the end
      product of RNase II. In addition, we present for the first time the models of two
      members of the RNase II family, RNase R from Escherichia coli and human Rrp44,
      also called Dis3. Our findings improve the present model for RNA degradation by
      the RNase II family of enzymes.

PMID- 18337247
TI  - A new small molecule inhibitor of estrogen receptor alpha binding to estrogen
      response elements blocks estrogen-dependent growth of cancer cells.
AB  - Estrogen receptor alpha (ERalpha) plays an important role in several human
      cancers. Most current ERalpha antagonists bind in the receptor ligand binding
      pocket and compete for binding with estrogenic ligands. Instead of the
      traditional approach of targeting estrogen binding to ER, we describe a strategy
      using a high throughput fluorescence anisotropy microplate assay to identify
      small molecule inhibitors of ERalpha binding to consensus estrogen response
      element (cERE) DNA. We identified small molecule inhibitors of ERalpha binding to
      the fluorescein-labeled (fl)cERE and evaluated their specificity, potency, and
      efficacy. One small molecule, theophylline, 8-[(benzylthio)methyl]-(7CI,8CI)
      (TPBM), inhibited ERalpha binding to the flcERE (IC(50) approximately 3 microm)
      and inhibited ERalpha-mediated transcription of a stably transfected ERE
      containing reporter gene. Inhibition by TPBM was ER-specific, because
      progesterone and glucocorticoid receptor transcriptional activity were not
      significantly inhibited. In tamoxifen-resistant breast cancer cells that
      overexpress ERalpha, TPBM inhibited 17beta-estradiol (E(2))-ERalpha (IC(50) 9
      microm) and 4-hydroxytamoxifen-ERalpha-mediated gene expression. Chromatin
      immunoprecipitation showed TPBM reduced E(2).ERalpha recruitment to an endogenous
      estrogen-responsive gene. TPBM inhibited E(2)-dependent growth of ERalpha
      positive cancer cells (IC(50) of 5 microm). TPBM is not toxic to cells and does
      not affect estrogen-independent cell growth. TPBM acts outside of the ER ligand
      binding pocket, does not act by chelating the zinc in ER zinc fingers, and
      differs from known ERalpha inhibitors. Using a simple high throughput screen for
      inhibitors of ERalpha binding to the cERE, a small molecule inhibitor has been
      identified that selectively inhibits ERalpha-mediated gene expression and
      estrogen-dependent growth of cancer cells.

PMID- 18337248
TI  - The second dimer interface of MT1-MMP, the transmembrane domain, is essential for
      ProMMP-2 activation on the cell surface.
AB  - Activation of proMMP-2 and cell surface collagenolysis are important activities
      of membrane-type 1 matrix metalloproteinase (MT1-MMP) to promote cell migration
      in tissue, and these activities are regulated by homodimerization of MT1-MMP on
      the cell surface. In this study, we have identified the transmembrane domain as a
      second dimer interface of MT1-MMP in addition to the previously identified
      hemopexin domain. Our analyses indicate that these two modes of dimerization have
      different roles; transmembrane-dependent dimerization is critical for proMMP-2
      activation, whereas hemopexin-dependent dimerization is important for degradation
      of collagen on the cell surface. Our finding provides new insight into the
      potential molecular arrangement of MT1-MMP contributing to its function on the
      cell surface.

PMID- 18337249
TI  - RNaseE and RNA helicase B play central roles in the cytoskeletal organization of
      the RNA degradosome.
AB  - The RNA degradosome of Escherichia coli is a multiprotein complex that plays an
      essential role in normal RNA processing and decay. It was recently shown that the
      major degradosome constituents are organized in a coiled cytoskeletal-like
      structure that extends along the length of the cell. Here we show that the
      endoribonuclease E (RNaseE) and RNA helicase B (RhlB) components of the
      degradosome can each independently form coiled structures in the absence of the
      other degradosome proteins. In contrast, the cytoskeletal organization of the
      other degradosome proteins required the presence of the RNaseE or RhlB coiled
      elements. Although the RNaseE and RhlB structures were equally competent to
      support the helical organization of polynucleotide phosphorylase, the
      cytoskeletal-like organization of enolase occurred only in the presence of the
      RNaseE coiled structure. The results indicate that the RNA degradosome proteins
      are components of the bacterial cytoskeleton rather than existing as randomly
      distributed multiprotein complexes within the cell and suggest a model for the
      cellular organization of the components within the helical degradosomal
      structure.

PMID- 18337250
TI  - Role of JNK translocation to mitochondria leading to inhibition of mitochondria
      bioenergetics in acetaminophen-induced liver injury.
AB  - Previously, we demonstrated JNK plays a central role in acetaminophen (APAP)
      induced liver injury (Gunawan, B. K., Liu, Z. X., Han, D., Hanawa, N., Gaarde, W.
      A., and Kaplowitz, N. (2006) Gastroenterology 131, 165-178). In this study, we
      examine the mechanism involved in activating JNK and explore the downstream
      targets of JNK important in promoting APAP-induced liver injury in vivo. JNK
      inhibitor (SP600125) was observed to significantly protect against APAP-induced
      liver injury. Increased mitochondria-derived reactive oxygen species were
      implicated in APAP-induced JNK activation based on the following: 1)
      mitochondrial GSH depletion (maximal at 2 h) caused increased H2O2 release from
      mitochondria, which preceded JNK activation (maximal at 4 h); 2) treatment of
      isolated hepatocytes with H2O2 or inhibitors (e.g. antimycin) that cause
      increased H2O2 release from mitochondria-activated JNK. An important downstream
      target of JNK following activation was mitochondria based on the following: 1)
      JNK translocated to mitochondria following activation; 2) JNK inhibitor treatment
      partially protected against a decline in mitochondria respiration caused by APAP
      treatment; and 3) addition of purified active JNK to mitochondria isolated from
      mice treated with APAP plus JNK inhibitor (mitochondria with severe GSH
      depletion, covalent binding) directly inhibited respiration. Cyclosporin A
      blocked the inhibitory effect of JNK on mitochondria respiration, suggesting JNK
      was directly inducing mitochondrial permeability transition in isolated
      mitochondria from mice treated with APAP plus JNK inhibitor. Addition of JNK to
      mitochondria isolated from control mice did not affect respiration. Our results
      suggests that APAP-induced liver injury involves JNK activation, due to increased
      reactive oxygen species generated by GSH-depleted mitochondria, and translocation
      of activated JNK to mitochondria where JNK induces mitochondrial permeability
      transition and inhibits mitochondria bioenergetics.

PMID- 18337251
TI  - Activated nuclear metabotropic glutamate receptor mGlu5 couples to nuclear Gq/11
      proteins to generate inositol 1,4,5-trisphosphate-mediated nuclear Ca2+ release.
AB  - Recently we have shown that the metabotropic glutamate 5 (mGlu5) receptor can be
      expressed on nuclear membranes of heterologous cells or endogenously on striatal
      neurons where it can mediate nuclear Ca2+ changes. Here, pharmacological,
      optical, and genetic techniques were used to show that upon activation, nuclear
      mGlu5 receptors generate nuclear inositol 1,4,5-trisphosphate (IP3) in situ.
      Specifically, expression of an mGlu5 F767S mutant in HEK293 cells that blocks
      Gq/11 coupling or introduction of a dominant negative Galphaq construct in
      striatal neurons prevented nuclear Ca2+ changes following receptor activation.
      These data indicate that nuclear mGlu5 receptors couple to Gq/11 to mobilize
      nuclear Ca2+. Nuclear mGlu5-mediated Ca2+ responses could also be blocked by the
      phospholipase C (PLC) inhibitor, U73122, the phosphatidylinositol (PI) PLC
      inhibitor 1-O-octadecyl-2-O-methyl-sn-glycero-3-phosphorylcholine (ET-18-OCH3),
      or by using small interfering RNA targeted against PLCbeta1 demonstrating that PI
      PLC is involved. Direct assessment of inositol phosphate production using a
      PIP2/IP3 "biosensor" revealed for the first time that IP3 can be generated in the
      nucleus following activation of nuclear mGlu5 receptors. Finally, both IP3 and
      ryanodine receptor blockers prevented nuclear mGlu5-mediated increases in
      intranuclear Ca2+. Collectively, this study shows that like plasma membrane
      receptors, activated nuclear mGlu5 receptors couple to Gq/11 and PLC to generate
      IP3-mediated release of Ca2+ from Ca2+-release channels in the nucleus. Thus the
      nucleus can function as an autonomous organelle independent of signals
      originating in the cytoplasm, and nuclear mGlu5 receptors play a dynamic role in
      mobilizing Ca2+ in a specific, localized fashion.

PMID- 18337252
TI  - Rad51 protein controls Rad52-mediated DNA annealing.
AB  - In Saccharomyces cerevisiae, Rad52 protein plays an essential role in the repair
      of DNA double-stranded breaks (DSBs). Rad52 and its orthologs possess the unique
      capacity to anneal single-stranded DNA (ssDNA) complexed with its cognate ssDNA
      binding protein, RPA. This annealing activity is used in multiple mechanisms of
      DSB repair: single-stranded annealing, synthesis-dependent strand annealing, and
      cross-over formation. Here we report that the S. cerevisiae DNA strand exchange
      protein, Rad51, prevents Rad52-mediated annealing of complementary ssDNA.
      Efficient inhibition is ATP-dependent and involves a specific interaction between
      Rad51 and Rad52. Free Rad51 can limit DNA annealing by Rad52, but the Rad51
      nucleoprotein filament is even more effective. We also discovered that the
      budding yeast Rad52 paralog, Rad59 protein, partially restores Rad52-dependent
      DNA annealing in the presence of Rad51, suggesting that Rad52 and Rad59 function
      coordinately to enhance recombinational DNA repair either by directing the
      processed DSBs to repair by DNA strand annealing or by promoting second end
      capture to form a double Holliday junction. This regulation of Rad52-mediated
      annealing suggests a control function for Rad51 in deciding the recombination
      path taken for a processed DNA break; the ssDNA can be directed to either Rad51
      mediated DNA strand invasion or to Rad52-mediated DNA annealing. This channeling
      determines the nature of the subsequent repair process and is consistent with the
      observed competition between these pathways in vivo.

PMID- 18337254
TI  - Expansion of substrate specificity and catalytic mechanism of azoreductase by X
      ray crystallography and site-directed mutagenesis.
AB  - AzoR is an FMN-dependent NADH-azoreductase isolated from Escherichia coli as a
      protein responsible for the degradation of azo compounds. We previously reported
      the crystal structure of the enzyme in the oxidized form. In the present study,
      different structures of AzoR were determined under several conditions to obtain
      clues to the reaction mechanism of the enzyme. AzoR in its reduced form revealed
      a twisted butterfly bend of the isoalloxazine ring of the FMN cofactor and a
      rearrangement of solvent molecules. The crystal structure of oxidized AzoR in a
      different space group and the structure of the enzyme in complex with the
      inhibitor dicoumarol were also determined. These structures indicate that the
      formation of a hydrophobic part around the isoalloxazine ring is important for
      substrate binding and an electrostatic interaction between Arg-59 and the
      carboxyl group of the azo compound causes a substrate preference for methyl red
      over p-methyl red. The substitution of Arg-59 with Ala enhanced the Vmax value
      for p-methyl red 27-fold with a 3.8-fold increase of the Km value. This result
      indicates that Arg-59 decides the substrate specificity of AzoR. The Vmax value
      for the p-methyl red reduction of the R59A mutant is comparable with that for the
      methyl red reduction of the wild-type enzyme, whereas the activity toward methyl
      red was retained. These findings indicate the expansion of AzoR substrate
      specificity by a single amino acid substitution. Furthermore, we built an
      authentic model of the AzoR-methyl red complex based on the results of the study.

PMID- 18337253
TI  - Enzymatic properties of an ecto-nucleoside triphosphate diphosphohydrolase from
      Legionella pneumophila: substrate specificity and requirement for virulence.
AB  - Legionella pneumophila is the predominant cause of Legionnaires disease, a severe
      and potentially fatal form of pneumonia. Recently, we identified an ecto
      nucleoside triphosphate diphosphohydrolase (NTPDase) from L. pneumophila, termed
      Lpg1905, which enhances intracellular replication of L. pneumophila in eukaryotic
      cells. Lpg1905 is the first prokaryotic member of the CD39/NTPDase1 family of
      enzymes, which are characterized by the presence of five apyrase conserved
      regions and the ability to hydrolyze nucleoside tri- and diphosphates. Here we
      examined the substrate specificity of Lpg1905 and showed that apart from ATP and
      ADP, the enzyme catalyzed the hydrolysis of GTP and GDP but had limited activity
      against CTP, CDP, UTP, and UDP. Based on amino acid residues conserved in the
      apyrase conserved regions of eukaryotic NTPDases, we generated five site-directed
      mutants, Lpg1905E159A, R122A, N168A, Q193A, and W384A. Although the mutations
      E159A, R122A, Q193A, and W384A abrogated activity completely, N168A resulted in
      decreased activity caused by reduced affinity for nucleotides. When introduced
      into the lpg1905 mutant strain of L. pneumophila, only N168A partially restored
      the ability of L. pneumophila to replicate in THP-1 macrophages. Following
      intratracheal inoculation of A/J mice, none of the Lpg1905 mutants was able to
      restore virulence to an lpg1905 mutant during lung infection, thereby
      demonstrating the importance of NTPDase activity to L. pneumophila infection.
      Overall, the kinetic studies undertaken here demonstrated important differences
      to mammalian NTPDases and different sensitivities to NTPDase inhibitors that may
      reflect underlying structural variations.

PMID- 18337255
TI  - Covalent inactivation of factor VIII antibodies from hemophilia A patients by an
      electrophilic FVIII Analog.
AB  - The antigen-binding sites of antibodies (Abs) can express enzyme-like
      nucleophiles that react covalently with electrophilic compounds. We examined the
      irreversible and specific inactivation of antibodies (Abs) to Factor VIII (FVIII)
      responsible for failure of FVIII replacement therapy in hemophilia A (HA)
      patients. Electrophilic analogs of FVIII (E-FVIII) and its C2 domain (E-C2) were
      prepared by placing the strongly electrophilic phosphonate groups at surface
      exposed Lys side chains of diverse antigenic epitopes. IgG Abs to FVIII from HA
      patients formed stable immune complexes with E-FVIII and E-C2 that were
      refractory to dissociation by SDS treatment and boiling, procedures that
      dissociate noncovalent Ab-antigen complexes. The rate-limiting step in the
      reaction was formation of the initial noncovalent complexes. Conversion of the
      initial complexes to the irreversible state occurred rapidly. The antigenic
      epitopes of E-FVIII were largely intact, and most of the Abs were consumed
      covalently. E-FVIII expressed poor FVIII cofactor activity in clotting factor
      assays. Nonspecific interference by E-FVIII in clotting factor function was not
      evident. Treatment with E-FVIII, and to a lesser extent E-C2, irreversibly
      relieved the FVIII inhibitory effect of HA IgG in clotting factor assays. Small
      FVIII peptides did not display useful reactivity, highlighting the diverse
      epitope specificities of the Abs and the conformational character of FVIII
      epitopes. E-FVIII is a prototype reagent able to attain irreversible and specific
      inactivation of pathogenic Abs.

PMID- 18337257
TI  - A nearest neighbor approach for automated transporter prediction and
      categorization from protein sequences.
AB  - MOTIVATION: Membrane transport proteins play a crucial role in the import and
      export of ions, small molecules or macromolecules across biological membranes.
      Currently, there are a limited number of published computational tools which
      enable the systematic discovery and categorization of transporters prior to
      costly experimental validation. To approach this problem, we utilized a nearest
      neighbor method which seamlessly integrates homologous search and topological
      analysis into a machine-learning framework. RESULTS: Our approach satisfactorily
      distinguished 484 transporter families in the Transporter Classification
      Database, a curated and representative database for transporters. A five-fold
      cross-validation on the database achieved a positive classification rate of 72.3%
      on average. Furthermore, this method successfully detected transporters in seven
      model and four non-model organisms, ranging from archaean to mammalian species. A
      preliminary literature-based validation has cross-validated 65.8% of our
      predictions on the 11 organisms, including 55.9% of our predictions overlapping
      with 83.6% of the predicted transporters in TransportDB.

PMID- 18337256
TI  - Invadopodia and matrix degradation, a new property of prostate cancer cells
      during migration and invasion.
AB  - The present study demonstrated that invadopodia are associated with invasion by
      degradation of matrix in prostate cancer cells PC3. To find out the presence of
      invadopodia in PC3 cells, we performed a few comparative analyses with
      osteoclasts, which utilize podosomes for migration. Our investigations indeed
      demonstrated that invadopodia are comparable to podosomes in the localization of
      Wiskott-Aldrich syndrome protein (WASP)/matrix metalloproteinase-9 and the
      degradation of matrix. Invadopodia are different from podosomes in the
      localization of actin/vinculin, distribution during migration, and the mode of
      degradation of extracellular matrix. Invadopodia enable polarized invasion of PC3
      cells into the gelatin matrix in a time-dependent manner. Gelatin degradation was
      confined within the periphery of the cell. Osteoclasts demonstrated directional
      migration with extensive degradation of matrix underneath and around the
      osteoclasts. A pathway of degradation of matrix representing a migratory track
      was observed due to the rearrangement of podosomes as rosettes or clusters at the
      leading edge. Reducing the matrix metalloproteinase-9 levels by RNA interference
      inhibited the degradation of matrix but not the formation of podosomes or
      invadopodia. Competition experiments with TAT-fused WASP peptides suggest that
      actin polymerization and formation of invadopodia involve the WASP-Arp2/3 complex
      pathway. Moreover, PC3 cells overexpressing osteopontin (OPN) displayed an
      increase in the number of invadopodia and gelatinolytic activity as compared with
      PC3 cells and PC3 cells expressing mutant OPN in integrin-binding domain and null
      for OPN. Thus, we conclude that OPN/integrin alphavbeta3 signaling participates
      in the process of migration and invasion of PC3 cells through regulating
      processes essential for the formation and function of invadopodia.

PMID- 18337258
TI  - A pattern recognition approach to infer time-lagged genetic interactions.
AB  - MOTIVATION: For any time-course microarray data in which the gene interactions
      and the associated paired patterns are dependent, the proposed pattern
      recognition (PARE) approach can infer time-lagged genetic interactions, a
      challenging task due to the small number of time points and large number of
      genes. PARE utilizes a non-linear score to identify subclasses of gene pairs with
      different time lags. In each subclass, PARE extracts non-linear characteristics
      of paired gene-expression curves and learns weights of the decision score
      applying an optimization algorithm to microarray gene-expression data (MGED) of
      some known interactions, from biological experiments or published literature.
      Namely, PARE integrates both MGED and existing knowledge via machine learning,
      and subsequently predicts the other genetic interactions in the subclass.
      RESULTS: PARE, a time-lagged correlation approach and the latest advance in
      graphical Gaussian models were applied to predict 112 (132) pairs of TC/TD
      (transcriptional regulatory) interactions. Checked against qRT-PCR results
      (published literature), their true positive rates are 73% (77%), 46% (51%), and
      52% (59%), respectively. The false positive rates of predicting TC and TD (AT and
      RT) interactions in the yeast genome are bounded by 13 and 10% (10 and 14%),
      respectively. Several predicted TC/TD interactions are shown to coincide with
      existing pathways involving Sgs1, Srs2 and Mus81. This reinforces the possibility
      of applying genetic interactions to predict pathways of protein complexes.
      Moreover, some experimentally testable gene interactions involving DNA repair are
      predicted. AVAILABILITY: Supplementary data and PARE software are available at
      http://www.stat.sinica.edu.tw/~gshieh/pare.htm.

PMID- 18337259
TI  - Optimizing the size of the sequence profiles to increase the accuracy of protein
      sequence alignments generated by profile-profile algorithms.
AB  - MOTIVATION: Profile-based protein homology detection algorithms are valuable
      tools in genome annotation and protein classification. By utilizing information
      present in the sequences of homologous proteins, profile-based methods are often
      able to detect extremely weak relationships between protein sequences, as
      evidenced by the large-scale benchmarking experiments such as CASP and LiveBench.
      RESULTS: We study the relationship between the sensitivity of a profile-profile
      method and the size of the sequence profile, which is defined as the average
      number of different residue types observed at the profile's positions. We also
      demonstrate that improvements in the sensitivity of a profile-profile method can
      be made by incorporating a profile-dependent scoring scheme, such as position
      specific background frequencies. The techniques presented in this article are
      implemented in an alignment algorithm UNI-FOLD. When tested against other well
      established methods for fold recognition, UNI-FOLD shows increased sensitivity
      and specificity in detecting remote relationships between protein sequences.
      AVAILABILITY: UNI-FOLD web server can be accessed at http://blackhawk.cs.uni.edu

PMID- 18337260
TI  - PlasmoGF: an integrated system for comparative genomics and phylogenetic analysis
      of Plasmodium gene families.
AB  - Malaria, one of the world's most common diseases, is caused by the intracellular
      protozoan parasite known as Plasmodium. Recently, with the arrival of several
      malaria parasite genomes, we established an integrated system named PlasmoGF for
      comparative genomics and phylogenetic analysis of Plasmodium gene families. Gene
      families were clustered using the Markov Cluster algorithm implemented in
      TribeMCL program and could be searched using keywords, gene-family information,
      domain composition, Gene Ontology and BLAST. Moreover, a number of useful
      bioinformatics tools were implemented to facilitate the analysis of these
      putative Plasmodium gene families, including gene retrieval, annotation, sequence
      alignment, phylogeny construction and visualization. In the current version,
      PlasmoGF contained 8980 sets of gene families derived from six malaria parasite
      genomes: Plasmodium. falciparum, P. berghei, P. knowlesi, P. chabaudi, P. vivax
      and P. yoelii. The availability of such a highly integrated system would be of
      great interest for the community of researchers working on malaria parasite
      phylogenomics. AVAILABILITY: PlasmoGF is freely available at
      http://bioinformatics.zj.cn/pgf/

PMID- 18337261
TI  - The Taverna Interaction Service: enabling manual interaction in workflows.
AB  - Taverna is an application that eases the integration of tools and databases for
      life science research by the construction of workflows. The Taverna Interaction
      Service extends the functionality of Taverna by defining human interaction within
      a workflow and acting as a mediation layer between the automated workflow engine
      and one or more users. AVAILABILITY: Taverna, the Interaction Service plug-in and
      web application are available as open source and can be downloaded from
      http://taverna.sourceforge.net/

PMID- 18337262
TI  - Medication adherence and quality of life in pediatric inflammatory bowel disease.
AB  - OBJECTIVE: To examine the relationship between medication adherence and quality
      of life (QOL) in adolescent patients with inflammatory bowel disease (IBD)
      utilizing a multimethod adherence assessment approach. METHODS: Medication
      adherence in 36 adolescents with IBD was assessed via interviews, pill counts,
      and biological assays. QOL was assessed via patient and parent report. Pediatric
      gastroenterologists provided disease severity assessments. RESULTS: Hierarchical
      multiple regression analyses revealed that adherence contributed significant
      variance to patient-reported QOL but not parent-reported QOL. Nonadherence to 6
      MP/azathioprine was related to poorer patient-reported physical health QOL.
      Greater self-reported 5-ASA adherence was related to poorer overall psychological
      health QOL, and particularly social functioning QOL. CONCLUSIONS: Results provide
      preliminary support for the negative effects of 6-MP/azathioprine nonadherence on
      QOL and an inverse relationship between 5-ASA adherence and QOL in this
      population. Adherence burden in patients and the utility of multimethod adherence
      assessment in research are discussed.

PMID- 18337263
TI  - Comment on: Is it ever appropriate to discharge patients with rheumatoid
      arthritis?

PMID- 18337264
TI  - Visceral leishmaniasis mimicking disease activity in mixed connective tissue
      disease.

PMID- 18337265
TI  - Comment on: Pyogenic sacroiliitis--a comparison between paediatric and adult
      patients.

PMID- 18337266
TI  - Improving the evidence base for treatment of juvenile idiopathic arthritis: the
      challenge and opportunity facing the MCRN/ARC Paediatric Rheumatology Clinical
      Studies Group.

PMID- 18337267
TI  - Resynchronization of the left ventricular contraction by tailored programming of
      right and left ventricular pacing.
AB  - AIMS: The prerequisite and the rationale for the benefit of cardiac
      resynchronization therapy (CRT) is that it is able to resynchronize left
      ventricular (LV) walls that have a delayed activation. METHODS AND RESULTS: In 69
      consecutive patients who underwent biventricular (BIV) pacemaker implantation, we
      assessed the magnitude of intraventricular resynchronization achieved by means of
      simultaneous (BIV 0) and sequential BIV pacing (with an individually optimized VV
      interval value among +80 ms and -80 ms) using pulsed-wave tissue Doppler imaging
      techniques and in particular the measurement of the intra-LV electromechanical
      delay. The intra-LV delay was defined as the difference between the longest and
      the shortest activation time in the six basal segments of the LV. An abnormal
      intra-LV delay was defined as a value >41 ms. The intra-LV delay was 63 +/- 28 ms
      baseline, decreased to 44 +/- 26 ms with BIV 0 and to 26 +/- 15 ms with optimized
      BIV (P = 0.001). BIV 0 determined the shortest delay in 28 (41%) patients (23 +/-
      12 ms). In 41 (59%) patients, a better resynchronization was achieved with
      optimized VV intervals (LV first in 32 and RV first in 5) or single-chamber
      pacing (LV in 3 and RV in 1). With BIV 0, the intra-LV delay remained abnormal in
      41% and was longer than baseline in 30% of patients compared with 9 and 12% with
      optimized BIV, respectively (P = 0.001). CONCLUSION: A sub-optimal
      resynchronization is achieved with simultaneous BIV pacing in most patients. A
      tailored programming of the relative contribution of RV and LV pacing forms the
      prerequisite for improving CRT results.

PMID- 18337268
TI  - Ventricular tachycardia with a myocardial fibre travelling from the origin in the
      right aortic sinus cusp to the epicardial breakout site of the right ventricular
      outflow tract.
AB  - A 74-year-old man with idiopathic ventricular tachycardia (VT) with a QRS
      morphology with a left bundle branch block and right inferior axis underwent
      electrophysiologic testing. Successful ablation was achieved at the right
      coronary cusp (RCC) where an excellent pace map with long stimulus-to-QRS
      interval (St-QRS) (85 ms) was obtained. An excellent pace map was also obtained
      on the epicardial surface approximately 1 cm away from the successful ablation
      site and the St-QRS was shorter (40 ms). These findings suggested that a
      myocardial fibre travelling from the origin in the RCC to the epicardium of the
      right ventricular outflow tract might exist.

PMID- 18337269
TI  - Gibberellin homeostasis in tobacco is regulated by gibberellin metabolism genes
      with different gibberellin sensitivity.
AB  - Gibberellins are phytohormones that regulate growth and development of plants.
      Gibberellin homeostasis is maintained by feedback regulation of gibberellin
      metabolism genes. To understand this regulation, we manipulated the gibberellin
      pathway in tobacco and studied its effects on the morphological phenotype,
      gibberellin levels and the expression of endogenous gibberellin metabolism genes.
      The overexpression of a gibberellin 3-oxidase (biosynthesis gene) in tobacco (3ox
      OE) induced slight variations in phenotype and active GA(1) levels, but we also
      found an increase in GA(8) levels (GA(1) inactivation product) and a conspicuous
      induction of gibberellin 2-oxidases (catabolism genes; NtGA2ox3 and -5),
      suggesting an important role for these particular genes in the control of
      gibberellin homeostasis. The effect of simultaneous overexpression of two
      biosynthesis genes, a gibberellin 3-oxidase and a gibberellin 20-oxidase
      (20ox/3ox-OE), on phenotype and gibberellin content suggests that gibberellin 3
      oxidases are non-limiting enzymes in tobacco, even in a 20ox-OE background.
      Moreover, the expression analysis of gibberellin metabolism genes in transgenic
      plants (3ox-OE, 20ox-OE and hybrid 3ox/20ox-OE), and in response to application
      of different GA(1) concentrations, showed genes with different gibberellin
      sensitivity. Gibberellin biosynthesis genes (NtGA20ox1 and NtGA3ox1) are
      negatively feedback regulated mainly by high gibberellin levels. In contrast,
      gibberellin catabolism genes which are subject to positive feedback regulation
      are sensitive to high (NtGA2ox1) or to low (NtGA2ox3 and -5) gibberellin
      concentrations. These two last GA2ox genes seem to play a predominant role in
      gibberellin homeostasis under mild gibberellin variations, but not under large
      gibberellin changes, where the biosynthesis genes GA20ox and GA3ox may be more
      important.

PMID- 18337270
TI  - Bispectral Index asymmetry and COMFORT score in paediatric intensive care
      patients.
AB  - BACKGROUND: The Bispectral Index (BIS) monitor has been suggested as a potential
      tool to measure depth of sedation in paediatric intensive care unit (PICU)
      patients. The primary aim of our observational study was to assess the difference
      in BIS values between the left and right sides of the brain. Secondary aims were
      to compare BIS and COMFORT score and to assess change in BIS with tracheal
      suctioning. METHODS: Nineteen ventilated and sedated PICU patients had paediatric
      BIS sensors applied to either side of their forehead. Each patient underwent
      physiotherapy involving tracheal suctioning. Their BIS data and corresponding
      COMFORT score, assessment as by their respective nurses, were recorded before,
      during, and after physiotherapy. RESULTS: Seven patients underwent more than one
      physiotherapy session; therefore, 28 sets of data were collected. The mean BIS
      difference values (and 95% CI) between left BIS and right BIS for pre-, during,
      and post-physiotherapy periods were 9.2 (5.9-12.5), 15.8 (11.9-19.7), and 7.5
      (5.2-9.7), respectively. Correlation between mean BIS, left brain BIS, and right
      brain BIS to COMFORT score was highly significant (P<0.001 for all three) during
      the pre- and post-physiotherapy period, but less so during the stimulated
      physiotherapy period (P=0.044, P=0.014, and P=0.253, respectively). CONCLUSIONS:
      A discrepancy between left and right brain BIS exists, especially when the
      patient is stimulated. COMFORT score and BIS correlate well between light and
      moderate sedation.

PMID- 18337271
TI  - Patient's satisfaction with perioperative care: development, validation, and
      application of a questionnaire.
AB  - BACKGROUND: Measuring patient satisfaction after anaesthesia care is complex. The
      existing patient satisfaction questionnaires are limited and omit aspects of
      patient satisfaction, such as professional competence, information provision,
      service, and staff-patient relationship. The aim of our study was to develop a
      valid and reliable self-reported multidimensional questionnaire assessing patient
      satisfaction that included these issues. METHODS: The development of the Leiden
      Perioperative care Patient Satisfaction questionnaire (LPPSq) was as follows:
      expert consultation, construction of the pilot questionnaire, pilot study,
      statistical analysis of the results of the pilot study (validity, reliability,
      and factor analysis), compilation of the definitive questionnaire, main study,
      and repeated statistical analysis (validity, reliability, and factor analysis).
      The overall patient satisfaction is expressed by the mean satisfaction score.
      RESULTS: Three hundred and eighty-two patients consented to participate in the
      study; 80.4% of the patients (n=307) completed the questionnaire. The LPPSq
      isolated three dimensions: information (Cronbach's alpha=0.82), fear and concern
      (Cronbach's alpha=0.69), and staff-patient relationship (Cronbach's alpha=0.94).
      Patient satisfaction with perioperative care was not directly dependent on the
      outcomes of anaesthesia but how patients were approached and the amount of
      information they received. Age (P=0.001), gender (P=0.001), work situation
      (P=0.003), and specialty (P=0.017) were the characteristics most influencing
      patient satisfaction. CONCLUSIONS: We developed the LPPSq questionnaire to
      measure patient satisfaction with perioperative care, of which anaesthesia care
      is an important element. In this study, information provision and the
      relationship between staff and patient were the major determinants of patient
      satisfaction.

PMID- 18337272
TI  - Short-term variations in response distribution to cortical stimulation.
AB  - Patterns of responses in the cerebral cortex can vary, and are influenced by pre
      existing cortical function, but it is not known how rapidly these variations can
      occur in humans. We investigated how rapidly response patterns to electrical
      stimulation can vary in intact human brain. We also investigated whether the type
      of functional change occurring at a given location with stimulation would help
      predict the distribution of responses elsewhere over the cortex to stimulation at
      that given location. We did this by studying cortical afterdischarges following
      electrical stimulation of the cortex in awake humans undergoing evaluations for
      brain surgery. Response occurrence and location could change within seconds, both
      nearby to and distant from stimulation sites. Responses might occur at a given
      location during one trial but not the next. They could occur at electrodes
      adjacent or not adjacent to those directly stimulated or to other electrodes
      showing afterdischarges. The likelihood of an afterdischarge at an individual
      site after stimulation was predicted by spontaneous electroencephalographic
      activity at that specific site just prior to stimulation, but not by overall
      cortical activity. When stimulation at a site interrupted motor, sensory or
      language function, afterdischarges were more likely to occur at other sites where
      stimulation interrupted similar functions. These results show that widespread
      dynamic changes in cortical responses can occur in intact cortex within short
      periods of time, and that the distribution of these responses depends on local
      brain states and functional brain architecture at the time of stimulation.
      Similar rapid variations may occur during normal intracortical communication and
      may underlie changes in the cortical organization of function. Possibly these
      variations, and the occurrence and distribution of responses to cortical
      stimulation, could be predicted. If so, interventions such as stimulation might
      be used to alter spread of epileptogenic activity, accelerate learning or enhance
      cortical reorganization after brain injury.

PMID- 18337273
TI  - Cerebral cortex and the clinical expression of Huntington's disease: complexity
      and heterogeneity.
AB  - The clinical phenotype of Huntington's disease (HD) is far more complex and
      variable than depictions of it as a progressive movement disorder dominated by
      neostriatal pathology represent. The availability of novel neuro-imaging methods
      has enabled us to evaluate cerebral cortical changes in HD, which we have found
      to occur early and to be topographically selective. What is less clear, however,
      is how these changes influence the clinical expression of the disease. In this
      study, we used a high-resolution surface based analysis of in vivo MRI data to
      measure cortical thickness in 33 individuals with HD, spanning the spectrum of
      disease and 22 age- and sex-matched controls. We found close relationships
      between specific functional and cognitive measures and topologically specific
      cortical regions. We also found that distinct motor phenotypes were associated
      with discrete patterns of cortical thinning. The selective topographical
      associations of cortical thinning with clinical features of HD suggest that we
      are not simply correlating global worsening with global cortical degeneration.
      Our results indicate that cortical involvement contributes to important symptoms,
      including those that have been ascribed primarily to the striatum, and that
      topologically selective changes in the cortex might explain much of the clinical
      heterogeneity found in HD. Additionally, a significant association between
      regional cortical thinning and total functional capacity, currently the leading
      primary outcome measure used in neuroprotection trials for HD, establishes
      cortical MRI morphometry as a potential biomarker of disease progression.

PMID- 18337274
TI  - Physical long-term health problems and mental comorbidity: evidence from Vietnam.
AB  - OBJECTIVE: The mental health of children living in low-income countries remains a
      neglected research area despite the high burden of disease. This study is one of
      the first that examines the effects of long-term physical health problems on
      child mental health disorders in a low-income country and investigates whether
      this association is modified by the socio-economic status of the child's family.
      METHODS: Community-based cross-sectional survey of 975 eight-year-old children
      from 20 sites in Vietnam. Long-term physical health problems were measured by a
      caregiver report and included conditions such as anaemia, congenital
      malformation, physical disability and skin problems. Child mental disorders were
      assessed using the strengths and difficulties questionnaire (SDQ). Generalised
      estimating equations models were fitted to explore the association between long
      term physical health problems and child mental disorders. RESULTS: Vietnamese
      children who suffer from long-term physical health problems have odds 2:1 times
      greater than children without long-term physical health problems of having a
      mental disorder (95% CI 1.2 to 3.6, p = 0.006). No significant interaction with
      socio-economic status was found. CONCLUSIONS: This study showed a high burden of
      mental disorders among physically ill children, re-enforcing the idea that there
      is "no health without mental health". While this association needs to be explored
      longitudinally, children with long-term health problems may be a visible group
      for targeted mental-health interventions.

PMID- 18337275
TI  - Acute otitis media in the first two months of life: characteristics and
      diagnostic difficulties.
AB  - OBJECTIVE: To assess the clinical and laboratory features of acute otitis media
      (AOM) in infants younger than 2 months, to look for factors predicting bacterial
      otitis, and to evaluate the accuracy of AOM diagnosis among paediatricians.
      METHODS: The study population comprised a cohort of 277 hospitalised infants up
      to 61 days old that were treated for the first episode of AOM in a paediatric
      department. We reviewed their medical records and analysed the demographic,
      clinical and laboratory data, and the diagnosis made by both paediatricians and
      otolaryngologists. RESULTS: Presenting symptoms were mainly respiratory (70.0%)
      and fever (62.5%). The most common pathogens were Streptococcus pneumoniae and
      Haemophilus influenzae. Gram-negative bacilli grew in 10.5% of the infants.
      Multivariate analysis revealed that AOM in the second month of life was
      associated with male gender, concurrent bronchiolitis and diarrhea. Although high
      leukocyte count was associated with bacterial pathogen, more than 70% of the
      patients with positive culture had normal white blood cell counts. The
      paediatrician diagnosed only 45% of the patients subsequently diagnosed with AOM
      by an otolaryngologist. CONCLUSIONS: The absence of predictors for bacterial
      infection in more than 70% of bacterial AOM suggests that empirical antibiotic
      treatment should be advised for the young infants with AOM even when afebrile and
      with normal laboratory profile. A low diagnostic rate of AOM by the paediatrician
      emphasizes the need for improvement in examination skills and instrumentation to
      allow a thorough ear evaluation in children of a very young age.

PMID- 18337276
TI  - Absence of urinary opioid peptides in children with autism.
AB  - OBJECTIVE: It has been claimed for a number of years that the urine of children
      with autism contains exogenously derived opioid peptides. This finding is said to
      reflect a disturbance in the integrity of the gut epithelium, act as a diagnostic
      marker for autism and predict treatment response to a diet excluding gluten and
      casein. The aim of the present study was to determine whether exogenous or
      endogenous peptides were present in the urine of children with autism or of
      control children. DESIGN: Case-control study SETTING: Cases were recruited from
      two tertiary referral centres specialising in autistic spectrum disorders, while
      controls were recruited from mainstream primary and secondary schools in the same
      geographical area. PARTICIPANTS: 65 boys with autism, mean age 7.4 years (range 5
      11) and 158 control boys, mean age 7.8 years (range 4.2-11). INVESTIGATIONS:
      Urine samples were examined by high pressure liquid chromatography (HPLC) and
      matrix assisted laser desorbtion ionisation-time of flight mass spectrometry
      (MALDI-TOF MS) for the presence of a number of putative opioid peptides.
      OUTCOMES: There were no significant differences between the HPLC urinary profiles
      of the children affected by autism and the typically developing controls. In
      those cases where HPLC showed peaks in the locations at which opioid peptides
      might be expected to be found, MALDI-TOF established that these peaks did not, in
      fact, represent opioid peptides. CONCLUSIONS: Given the lack of evidence for any
      opioid peptiduria in children with autism, opioid peptides can neither serve as a
      biomedical marker for autism nor be employed to predict or monitor response to a
      casein- and gluten-free diet.

PMID- 18337278
TI  - Multi-method evaluation of a paediatric ambulatory care unit (PACU): impact on
      families and staff.
AB  - AIM: To assess the impact of a purpose-built, short stay paediatric ambulatory
      care unit (PACU) on the patient journey and perceptions of parents, staff and
      referrers. METHODS: Multi-method evaluation, including a parent survey (n = 104),
      patient journey mapping (n = 10), staff interviews (n = 10), a referrer survey (n
      = 16), routine activity analysis, and a comparison with the A&E service (A&E
      parent survey: n = 41). RESULTS: Almost all parents attending PACU (94%) were
      satisfied with the service and significantly more likely to feel "very" satisfied
      than parents attending A&E (PACU: 51%, A&E: 31%; p = 0.03). Further, over three
      quarters (77%) of PACU parents preferred the new model to traditional A&E
      services. They reported receiving sufficient information (93%), reduced anxiety
      (55% anxious before service, 13% anxious after; p<0.001), "quick" waiting times
      (median: 35 min), and enhanced confidence (87%) and understanding (89%) in
      dealing with their ill child. The number of stages in the patient journey was
      reduced from six ("traditional" A&E pathway) to four (PACU pathway). Staff and
      referrers reported this was a "superior" model to A&E, but that improvements were
      required around appropriate referrals and the need for more multi-disciplinary
      protocols and liaison. CONCLUSION: Our study suggests that the PACU model is
      perceived to be an effective alternative to standard A&E services for the
      assessment and early management of acutely ill children and their families
      attending a hospital. It is highly valued by users, staff and referrers and
      enhances the patient journey. Lessons learnt include the need to enhance multi
      disciplinary processes and clarify the role of this form of acute care provision
      in the wider healthcare system.

PMID- 18337279
TI  - Effect of education and safety equipment on poisoning-prevention practices and
      poisoning: systematic review, meta-analysis and meta-regression.
AB  - OBJECTIVE: To assess (a) the effect of home safety education and the provision of
      safety equipment on poison-prevention practices and poisoning rates, and (b)
      whether the effect of interventions differs by social group. DATA SOURCES:
      Medline, Embase, Cinahl, ASSIA, Psychinfo, Web of Science, plus other electronic
      sources and hand searching of conference abstracts and reference lists. Authors
      of included studies were asked to supply individual participant data. REVIEW
      METHODS: Randomised controlled trials, non-randomised controlled trials and
      controlled before-and-after studies, with participants aged </=19 years,
      providing home safety education with or without free or subsidised safety
      equipment and reporting poison-prevention practices or poisoning incidents were
      included. Pooled odds ratios and pooled rate ratios were estimated, and meta
      regression estimated intervention effects by child age, gender and social
      variables. RESULTS: Home safety interventions increased safe storage of medicines
      (OR 1.57, 95% CI 1.22 to 2.02) and cleaning products (OR 1.63, 95% CI 1.22 to
      2.17), the possession of syrup of ipecac (OR 3.34, 95% CI 1.50 to 7.41), and
      having poison control centre numbers accessible (OR 3.67, 95% CI 1.84 to 7.33).
      There was a lack of evidence on poisoning rates (rate ratio 1.03, 95% CI 0.78 to
      1.36) and no consistent evidence that intervention effects differed by child age,
      gender or social group. CONCLUSIONS: Home safety education and the provision of
      safety equipment improve poison-prevention practices, but the impact on poisoning
      rates is unclear. Such interventions are unlikely to widen inequalities in
      childhood poisoning-prevention practices.

PMID- 18337280
TI  - Efficacy and safety of torasemide in children with heart failure.
AB  - OBJECTIVE: To examine the efficacy and safety of torasemide in children with
      chronic heart failure (HF). METHODS: 102 children with chronic HF who had
      received oral torasemide were analysed. Of these, 62 (de novo group) were newly
      diagnosed as having HF and were given torasemide as a diuretic. The remaining 40
      (replacement group) had been given furosemide for >3 months before the study, and
      furosemide was then replaced with torasemide. Clinical signs and symptoms of HF
      (assessed as the HF index), humoral factors and serum potassium concentrations
      before torasemide treatment were compared with those obtained 3-4 weeks after
      torasemide treatment. Patients were also monitored for adverse effects. RESULTS:
      In the de novo group, torasemide significantly improved the HF index with
      concomitant improvement in plasma brain natriuretic peptide concentration (median
      (interquartile range) 52 (51) vs 43 (49) pg/ml). In a randomly selected group of
      25 de novo patients with ventricular septal defect, echocardiography showed that
      torasemide significantly improved left ventricular geometry and function. In the
      replacement group, brain natriuretic peptide concentrations were also
      significantly decreased from 50 (104) to 45 (71) pg/ml after substitution of
      torasemide, but the HF index showed only a tendency for improvement (p = 0.07).
      Torasemide also had a potassium-sparing effect (de novo group, no change in
      potassium concentration; replacement group, significant increase from 4.2 (0.5)
      to 4.3 (0.5) mEq/l), and caused a significant rise in serum aldosterone
      concentration, consistent with the anti-aldosterone effect of this drug. Serum
      concentrations of sodium and uric acid had not changed after torasemide
      treatment, and there were no serious adverse events that necessitated drug
      withdrawal. CONCLUSION: Torasemide can be safely used, and appears to be
      effective for treatment of HF in children. Future clinical trials are warranted
      to verify the present results.

PMID- 18337281
TI  - Juvenility in the context of life history theory.
AB  - Homo sapiens is unique in having four prolonged and pronounced postnatal pre
      adult life history stages: infancy, which lasts for 30-36 months and ends with
      weaning from breast feeding in traditional societies; childhood, which lasts for
      an additional 2-4 years and concludes in a degree of independence as regards
      protection and food provision; a juvenile stage of 3-4 years that terminates with
      readiness for sexual maturation; and adolescence, which lasts for 3-5 years and
      culminates in fertility. Juvenility implies two transitional periods which are
      only experienced by humans: a transition from childhood to juvenility and from
      juvenility to adolescence. Juvenility, "the age of reason and responsibility" and
      concrete operation, coincides with elementary school age and offers opportunities
      to prepare for the social complexity of adolescence. Here I define the transition
      to juvenility by three variables: adrenarche (the onset of adrenal androgen
      generation), growth pattern (decelerating from a linear childhood growth
      velocity) and adiposity rebound acceleration of body mass index. The data
      presented suggest that this period is endowed with programming/predictive
      adaptive responses of body composition to the environment.

PMID- 18337282
TI  - Early rattles, purrs and whistles as predictors of later wheeze.
AB  - BACKGROUND: Asthma is a common condition characterised by wheeze. Many different
      respiratory sounds are interpreted by parents as "wheeze" in young children. AIM:
      To relate different respiratory sounds reported as wheeze in 2-year-olds to
      asthma outcomes at age 5 years. METHODS: As part of a longitudinal cohort study,
      parents completed respiratory questionnaires for their children at 2 and 5 years
      of age. Parents who reported wheeze were given options to describe the sound as
      rattling, purring or whistling. RESULTS: Of the 1371 2-year-olds surveyed, 210
      had current wheeze, of whom 124 had rattle, 49 purr and 24 whistle. Children with
      whistle at 2 years were more likely to have mothers with asthma, and children
      with rattle and purr were more likely to be exposed to tobacco smoke. Wheeze
      status was ascertained at age 5 years in 162 (77%) children with wheeze at 2
      years of age. Whistle persisted in 47% of affected children, rattle in 20%, and
      purr in 13% (p = 0.023). At 5 years of age, asthma medication was prescribed in
      40% with whistle, 11% with rattle, and 18% with purr at 2 years of age (p =
      0.017). CONCLUSIONS: This study shows different risk factors and outcomes for
      different respiratory sounds in 2-year-olds: compared with other respiratory
      sounds, whistle is likely to persist and require asthma treatment in future.

PMID- 18337283
TI  - Characterisation and evaluation of UK websites on attention deficit hyperactivity
      disorder.
AB  - OBJECTIVES: To identify, characterise and evaluate UK websites providing
      information about attention deficit hyperactivity disorder (ADHD) and its
      pharmacological management. DESIGN: Cross-sectional survey of websites identified
      by entering "ADHD" into five search engines. DATA SOURCE: 48 websites. MAIN
      OUTCOME MEASURES: Each website was scored against 26 criteria using a bespoke
      instrument to evaluate (a) quality of information on the disorder and its drug
      treatment and (b) physical characteristics of the site. RESULTS: Most sites (n =
      22) were hosted by charities and support groups, 12 were by commercial
      organisations, nine were from government or professional bodies, and five were
      categorised as miscellaneous. Mean total scores per host category ranged from
      18.8 to 21 out of 46, with mean (SD) scores of 5.5 (4.2) out of 28 for content
      and 14.8 (3.0) out of 18 for physical properties. The government/professional
      sites scored highest for both content and physical properties. Descriptions of
      the disorder and its drug treatment were poor and lacking in detail. Although
      most sites mentioned stimulants, only eight discussed atomoxetine and described
      how both types of drug worked. Ten sites provided detailed information about side
      effects. The role of different stimulant brands and formulations was discussed on
      six sites. Authorship details were generally vague. Physical properties related
      to navigation and layout performed well. Only four sites used language deemed
      suitable for consumer-orientated health information. CONCLUSIONS: Information on
      UK websites about drug treatment for ADHD is basic and incomplete. Websites by
      government and professional bodies perform better than those in other categories.

PMID- 18337284
TI  - Once-daily amoxicillin versus twice-daily penicillin V in group A beta-haemolytic
      streptococcal pharyngitis.
AB  - BACKGROUND: Rheumatic fever is a preventable chronic disease preceded by group A
      beta-haemolytic streptococcal (GABHS) pharyngitis. OBJECTIVE: To test the non
      inferiority of once-daily (QD) oral amoxicillin to the recommended twice-daily
      (BID) oral penicillin V in GABHS pharyngitis. METHODS: This was a randomised non
      inferiority trial carried out in a school-based clinic in New Zealand. Children
      presenting with GABHS pharyngitis were randomised to oral amoxicillin 1500 mg QD
      (or 750 mg if bodyweight was <or=30 kg) or to oral penicillin V 500 mg BID (or
      250 mg if bodyweight was <or=20 kg) for 10 days. Observed medication and weekend
      diary cards were used to monitor adherence. OUTCOME: Eradication of GABHS,
      determined with follow-up throat cultures on days 3-6, 12-16 and 26-36. GABHS
      isolates were serotyped to distinguish bacteriological treatment failures (and
      relapses) from new acquisitions. Non-inferiority was defined as an upper 95%
      confidence limit (CL) for the difference in success of eradication in the
      amoxicillin and penicillin V treatment groups of <or=10%. RESULTS: 353 children
      with positive throat swabs for GABHS were randomised to amoxicillin (n = 177) or
      penicillin V (n = 176). The upper 95% CL for the differences in positive cultures
      between the antibiotics was 4.9% at days 3-6, 6.5% at days 12-16 and 8.5% at days
      26-36. Treatment failures (including relapses) occurred at each visit in 5.8%,
      12.7% and 10.7% of amoxicillin recipients and 6.2%, 11.9% and 11.3% of penicillin
      V recipients, respectively. No significant differences in resolution of symptoms
      were noted between treatment groups. One case of unsubstantiated acute rheumatic
      fever occurred after 7 days of amoxicillin. CONCLUSION: In this adequately
      powered study, once-daily oral amoxicillin is not inferior to twice-daily
      penicillin V for the treatment and eradication of GABHS in children with
      pharyngitis.

PMID- 18337285
TI  - High rate of maternal vitamin B12 deficiency nearly a decade after Canadian folic
      acid flour fortification.
AB  - Vitamin B12 deficiency may be an independent risk factor for neural tube defects
      (NTD). We determined the prevalence of biochemical B12 deficiency (<125 pmol/l)
      among 10 622 Ontarian women aged 15-46 years who underwent concomitant testing of
      serum bhCG and B12 9 years after the implementation of Canadian folic acid flour
      fortification. The overall prevalence of biochemical B12 deficiency was 7.4%.
      Relative to non-pregnant women, the adjusted odds ratio (95% confidence interval)
      of biochemical B12 deficiency was 0.78 (0.60-1.0) among women pregnant 28 days
      gestation or less and was 1.4 (1.1-1.8) after 28 days gestation. About 1 in 20
      women may be deficient in B12 in early pregnancy. The impact on maternal and
      fetal well-being, including preventable NTD, should be considered.

PMID- 18337286
TI  - Attitudes toward the large-scale implementation of an incident reporting system.
AB  - OBJECTIVE: An electronic Incident Information Management System implemented
      system-wide by the Department of Health, New South Wales, Australia was
      evaluated. We hypothesized that health professionals (i) would support the system
      via utilization and favourable attitudes and (ii) that their usage and attitudes
      would vary according to profession with nurses being most, and doctors least,
      favourably disposed. DESIGN, SETTING AND PARTICIPANTS: An online, anonymous
      questionnaire survey of 2185 health practitioners. MAIN OUTCOME MEASURES:
      Undertaking system training, satisfaction with training, reporting incidents,
      incident reporting rates since system introduction and attitude questions
      focusing on use, security and evaluation of the system and workplace safety
      cultures. RESULTS: The first hypothesis received partial support. The majority of
      respondents had undertaken training and rated it highly. Most had reported
      incidents and maintained their previous reporting levels. Most attitudes
      regarding using the system and its security were favourable. Mixed attitudes were
      held about workplace safety cultures and the value of the system. Deficiencies in
      quality of reporting, feedback on incident reports and resources to analyse
      incident data were problems identified. The second hypothesis was confirmed.
      Nurses were most, and doctors least, likely to undertake training, report
      incidents and express favourable attitudes. Allied health responses were
      intermediate to those of the other professions. CONCLUSIONS: The system
      implementation was relatively successful, but more so with some professions.
      Problems identified indicated that expectations as to the goals achievable in the
      short term were optimistic, but these are amenable to planned interventions.

PMID- 18337287
TI  - Conformity of commercial oral single solid unit dose packages in hospital
      pharmacy practice.
AB  - BACKGROUND: There are limited published data on the labelling of single unit dose
      packages in hospitals. SETTING AND PARTICIPANTS: The study was conducted in three
      large hospitals (two adult and one paediatric) in the metropolitan Montreal area,
      Quebec, Canada. OBJECTIVE: The objective is to evaluate the labelling of
      commercial oral single solid unit dose packages available in Canadian urban
      hospital pharmacy practice. METHOD: The study endpoint was the labelling
      conformity of each unit dose package for each criterion and overall for each
      manufacturer. Complete labelling of unit dose packages should include the
      following information: (1) brand name, (2) international non-proprietary name or
      generic name, (3) dosage, (4) pharmaceutical form, (5) manufacturer's name, (6)
      expiry date, (7) batch number and (8) drug identification number. We also
      evaluated the ease with which a single unit dose package is detached from a
      multiple unit dose package for quick, easy and safe use by pharmacy staff.
      Conformity levels were compared between brand-name and generic packages. RESULTS:
      A total of 124 different unit dose packages were evaluated. The level of
      conformity of each criterion varied between 19 and 50%. Only 43% of unit dose
      packages provided an easy-to-detach system for single doses. Among the 14
      manufacturers with three or more unit dose packages evaluated, eight (57%) had a
      conformity level less than 50%. CONCLUSION: This study describes the conformity
      of commercial oral single solid unit dose packages in hospital pharmacy practice
      in Quebec. A large proportion of unit dose packages do not conform to a set of
      nine criteria set out in the guidelines of the American Society of Health-System
      Pharmacists and the Canadian Society of Hospital Pharmacists.

PMID- 18337288
TI  - Mixed- and general-order kinetics applied to selected thermoluminescence glow
      curves.
AB  - Mixed-order (MO) and general-order (GO) kinetics expressions are applied to
      experimental glow curves of CaSO4:Ce, LiNaSO4:Eu, BaF2:Ce and SrF2:Er. The
      purpose is to compare the activation energies derived from the two models to
      investigate the correlation between the order of kinetics, b, and the parameter
      alpha of the MO model for real systems and to explore the validity of the
      correlation between b and alpha derived from the analysis of synthetic glow peaks
      or experimentally isolated single peak for complex glow curves. The two
      alternative routes resulted in clean fits with very close values of the sum of
      squared residuals. The general conclusions are: (1) the activation energies
      derived from the MO model are slightly higher than the ones derived from the GO
      model, but the difference appears to be insignificant, (2) the correlation
      between b and alpha is not smooth and the scatter in the b values for a given
      alpha is within the theoretically expected spread in the b value and (3) the MO
      expression is capable of evaluating the shape parameters as accurately as the GO
      expression with the advantage that it has a physical basis contrary to the purely
      empirical GO model.

PMID- 18337289
TI  - AIDE: internal dosimetry software.
AB  - AIDE (Activity and Internal Dose Estimates) is a software for calculating
      activities in compartments and committed doses due to occupational exposures, and
      for performing intake and dose estimates using bioassay data. It has been
      continuously developed and tested for more than 20 years. Its calculation core
      has been applied in several situations, like performing all dose estimates due to
      (137)Cs intakes, which occurred during the Goiania accident in 1987; performing
      quality assurance of the ICRP Task Group on Dose Calculations regarding
      calculations of activities in compartments and generation of dose coefficients
      for adults due to intakes by inhalation, ingestion and injection of several
      radionuclides; and producing the tables of activities in compartments and dose
      coefficients using the NCRP Wound Model for the NCRP report. It provides several
      capabilities like performing calculations using modified Human Respiratory Tract
      Model parameters for the mechanical transport, blood absorption and partitions of
      deposit in the AI region. The existing systemic models can also be modified or
      new ones can be entered. All estimate procedures are in accordance with the
      methods presented in the ICRP-78 Publication, in the IAEA Safety Reports Series
      no. 37 and in the IDEAS Project Guidelines 2006.

PMID- 18337290
TI  - High patient doses in interventional cardiology due to physicians' negligence:
      how can they be prevented?
AB  - Interventional cardiology procedures are usually associated with high patient
      doses and even deterministic radiation effects may occur. Expensive digital flat
      panels are preferably used to lower doses, and Athens General Hospital has
      recently installed one. However, this study shows that it is the cardiologists'
      practice that lowers patients' doses. Doses delivered to patients during two time
      periods (pre and after radiation protection training) on a total of 1196 coronary
      angiographies and 506 percutaneous transluminal coronary angioplasties were
      measured and analysed per cardiologist. Local reference levels (LRLs) were
      assessed and compared with the preliminary RLs provided by the European Research
      Program DIMOND. Results showed that although after the training patients' dose
      area product, fluoroscopy time, cumulative dose and number of images acquired
      were lowered, the situation remained unchanged for the cardiologist who delivered
      the highest doses. The question to answer next is how this bad practice can be
      prevented since no dose constraints apply to diagnostic or therapeutic procedures
      using ionising radiation.

PMID- 18337291
TI  - Sizing particles of natural uranium and nuclear fuels using poly-allyl-diglycol
      carbonate autoradiography.
AB  - Theoretical and experimental methods were developed to assess the size
      distribution of alpha-emitting particles captured on air-sampler filters. The
      particle size of oxides of low enriched, depleted and natural uranium and also
      aged plutonium in mixed oxide reactor fuels of known composition was determined
      using poly-allyl-diglycol carbonate (PADC) autoradiography, the commercial
      product TASTRAK((R)), solid-state nuclear track detectors. The exposed PADC was
      chemically etched to reveal clusters of tracks, radially dispersing from central
      points. A theoretical model was developed which converted the number of tracks in
      a track cluster to the hot particle diameter. The diameters of 26 particles of
      natural uranium oxide were measured (4-130 microm) using an optical microscope.
      There was a good agreement between these particle size measurements and a
      theoretical assessment based on the track cluster count.

PMID- 18337292
TI  - Age-dependent potassium iodide effect on the thyroid irradiation by 131I and 133I
      in the nuclear emergency.
AB  - The initial near-field exposure is primarily through inhalation in a nuclear
      emergency and the dominant contribution to the effective inhalation dose comes
      from radioiodine. Thyroid blockade by oral potassium iodide (KI) is efficient and
      practical for public in the nuclear emergency. Age-dependent radioprotective
      effect of KI on the thyroid irradiation by (131)I and (133)I has been derived
      using the simplified compartment model of iodine metabolism and WinSAAM program.
      Administration of KI within 2 h after (131)I and (133)I intake can block thyroid
      uptake significantly, yielding protective effect of 78.9% and 74.3%,
      respectively, for (131)I and (133)I for adults. The mean absorbed doses decrease
      with age, while protective effects of KI are similar for all age groups.

PMID- 18337293
TI  - Natural radioactivity and external gamma radiation exposure at the coastal Red
      Sea in Egypt.
AB  - Radionuclides which present in different beach sands are sources of external
      exposure that contribute to the total radiation exposure of human. In this work,
      superficial samples of beach sand were collected from the Red Sea coastline (Ras
      Gharib, Hurghada, Safaga, Qusier and Marsa Alam areas) and at 20 km on Qena
      Safaga road. The distribution of natural radionuclides in sand beach samples was
      studied by gamma spectrometry. The activity concentrations of primordial and
      artificial radionuclides in samples that are collected from the coastal
      environment of the Red Sea were 19.2 +/- 3 Bq kg(-1) for (210)Pb, 21.1 +/- 1 Bq
      kg(-1) for (226)Ra, 22.7 +/- 2 Bq kg(-1) for (238)U, 1.0 +/- 0.1 Bq kg(-1) for
      (235)U, 11.6 +/- 1 Bq kg(-1) for (228)Ra, 13.0 +/- 1 Bq kg(-1) for (228)Th, 12.4
      +/- 1 Bq kg(-1) for (232)Th, 930 +/- 32 Bq kg(-1) for (40)K and 1.2 +/- 0.3 Bq
      kg(-1) for (137)Cs. The mean external gamma-dose rate was 62.5 +/- 3.2 nSv h(-1),
      54.4 +/- 2.8 nGy h(-1) Ra equivalent activity (Ra(eq)) was 107 +/- 5.8 Bq kg(-1),
      0.86 +/- 0.04 Bq kg(-1) for representative level index (I(gamma)) and effective
      dose rate was 0.067 +/- 0.003 mSv y(-1) in beach sand red sea, in air due to
      naturally occurring radionuclides.

PMID- 18337294
TI  - Normalisation of spot urine samples to 24-h collection for assessment of exposure
      to uranium.
AB  - For dose assessment of workers at Nuclear Research Center Negev exposed to
      natural uranium, spot urine samples are analysed and the results are normalised
      to 24-h urine excretion based on 'standard' man urine volume of 1.6 l d(-1). In
      the present work, the urine volume, uranium level and creatinine concentration
      were determined in two or three 24-h urine collections from 133 male workers (319
      samples) and 33 female workers (88 samples). Three volunteers provided urine spot
      samples from each voiding during a 24-h period and a good correlation was found
      between the relative level of creatinine and uranium in spot samples collected
      from the same individual. The results show that normalisation of uranium
      concentration to creatinine in a spot sample represents the 24-h content of
      uranium better than normalisation to the standard volume and may be used to
      reduce the uncertainty of dose assessment based on spot samples.

PMID- 18337295
TI  - Effect of moisture on the radon exhalation rate from soil, sand and brick samples
      collected from NWFP and FATA, Pakistan.
AB  - A series of experiments were carried out to study the effect of the moisture
      content on the radon exhalation rate from soil, sand and brick samples that were
      collected from the North West Frontier Province and Federally Administered Tribal
      Areas of Pakistan, using CR-39-based radon dosimeters. After processing, samples
      were prepared by adding 15, 30 and 45% moisture contents (by weight) and were
      placed in plastic containers. The dosimeters were installed in it at heights of
      25 cm above the surface of the samples. These containers were then hermetically
      sealed and the dosimeters were exposed to radon for 60 to 65 days. After
      exposure, CR-39 detectors were etched in 25% NaOH at 80 degrees C for 16 h, and
      track densities were counted. From the measured track densities, exhalation rate
      was determined using two different approaches. Maximum average radon exhalation
      rates of 385 +/- 86, 393 +/- 31 and 362 +/- 36 mBq m(-2) h(-1) were observed at
      30% moisture content from soil, sand and brick samples, respectively. A slight
      decrease in exhalation rate was observed in all samples at moisture content of
      45%. According to the t-test, change in the exhalation rate as a function of
      humidity is significant at 95% confidence level.

PMID- 18337296
TI  - Surface dose measurement in patients and physicians and effective dose estimation
      in patients during uterine artery embolisation.
AB  - Surface dose monitoring in patients and physicians during 29 uterine artery
      embolisation (UAE) procedures was performed using photoluminescence dosemeters
      and thermo-luminescence dosemeters. Organ or tissue doses were measured with an
      anthropomorphic phantom using UAE exposure conditions averaged from the 29 cases,
      and effective doses were estimated for the patient. Entrance surface dose of the
      patients at the maximum dose position ranged from 121.5 to 1650 mGy. Estimated
      doses ranged from 3.16 to 43 mGy for the ovary and from 3.8 to 51.8 mGy for the
      uterus. The effective dose was 1.09-14.8 mSv. Monitored doses on the body surface
      of physicians were relatively high in the upper arm (5.41+/-1.52 to 163+/-17.25
      microGy) and the hand and fingers (0.85+/-1.18 to 222+/-16.4 microGy).

PMID- 18337298
TI  - A decade on: what have we learnt about supporting women with intellectual
      disabilities through the menopause?
AB  - Carr and Hollins highlighted the paucity of research on the menopause in women
      with intellectual disabilities and, 10 years on, this area still remains poorly
      researched. Work exploring the age of onset of the menopause has suggested that
      the menopause is earlier in this group of women, but studies exploring what women
      with intellectual disabilities understand and experience during the menopause are
      limited. In this study 15 women with mild to moderate intellectual disabilities
      were interviewed using a semi-structured interview on a one-to-one basis about
      their knowledge and understanding of the menopause. Findings revealed limited
      accessible information about the menopause and a paucity in the women's knowledge
      and understanding about the menopause. This suggests a need for more accessible
      information, in order to increase understanding and awareness of the menopause in
      these women.

PMID- 18337299
TI  - Psycho-educational groups for people with a dual diagnosis of psychosis and mild
      intellectual disability: a preliminary study.
AB  - There have been considerable developments in psychosocial interventions for
      people with psychosis, but few studies on their application to individuals with a
      dual diagnosis of intellectual disability and psychosis. This includes the use of
      psycho-educational groups to develop a greater understanding of the impact of
      psychosis. Eight individuals with a dual diagnosis of mild to borderline
      intellectual disabilities and psychosis took part in a psycho-education group
      supported by a carer. Measures of knowledge and self-esteem were completed pre-
      and post-group. All participants completed the programme and measures of
      psychosis knowledge showed increases post-group. The participants were able to
      understand the concept of psychosis, the need for medication, the role of stress
      and early signs of relapse. This approach may help participants to have a better
      understanding of their condition and prepare them to cope better in the future.

PMID- 18337300
TI  - Hereditary spastic paraplegia, bipolar affective disorder and intellectual
      disability: a case report.
AB  - This is a case report of a gentleman with an intellectual impairment who
      presented with both hereditary spastic paraplegia (HSD) and bipolar affective
      disorder (BPAD), a combination that has not yet been described in the
      professional literature. A limited number of articles have suggested an
      association between HSP and an organic personality disorder. We describe the case
      of a gentleman who was diagnosed with BPAD in his early adult life and displayed
      neurological symptoms of HSP at around the same time. Diagnosis of both HSP and
      BPAD can be difficult and is further compounded by an intellectual impairment.
      Treatment options may be limited by the propensity of many psychotropic
      medications to cause movement disorders and thus worsening neurological symptoms.

PMID- 18337301
TI  - The use of the Social Cognitive Skills Test with children with autistic spectrum
      disorders.
AB  - With increased diagnosis of autistic spectrum disorder (ASD) and the wide range
      of ability within this diagnosis, appropriate and accurate appraisal of specific
      ability are necessary to increase understanding of behaviour and inform effective
      intervention. The Social Cognitive Skills Test (SCST) focuses on the assessment
      of social reasoning skills. The present study investigated whether the SCST can
      usefully measure social reasoning ability in children with ASD. Eight children
      with ASD and eight typically developing children aged 5-13 years, who were
      matched on verbal comprehension, block design score and gender, took part in this
      pilot study. A decreasing trend in scores as the complexity of social cognitive
      skills increased was noted together with a significant difference between the two
      groups on three out of four social cognitive levels. This pilot study suggests
      the applicability of the SCST for use with children with ASD to assess social
      reasoning abilities.

PMID- 18337302
TI  - Community learning disability teams: developments, composition and good practice:
      a review of the literature.
AB  - This article presents the findings from a literature review related to community
      learning disability teams (CLDTs). Much of the existing literature on CLDTs is
      inspirational, theoretical or opinion based rather than evidence based. It was
      considered that current knowledge is insufficient to allow a systematic review;
      therefore a structured review of factors that impact on CLDTs was undertaken
      following some of the principles of a systematic review. The review covers
      historical and philosophical influences on the development of CLDTs; the
      structure and common composition of CLDTs; the main challenges facing CLDTs; and
      the barriers that impact on their effective working. Based on the available
      evidence a number of good practice suggestions are forwarded that have the
      potential to enhance the work undertaken by CLDTs, but it is acknowledged that
      there is a need for more research into the effectiveness of these teams.

PMID- 18337303
TI  - Screening for depressive symptoms: validation of the center for epidemiologic
      studies depression scale (CES-D) in a multiethnic group of patients with diabetes
      in Singapore.
AB  - OBJECTIVE: We determined the reliability and validity of the Center for
      Epidemiologic Studies Depression Scale (CES-D) against the DSM-IV-based
      diagnostic inventory, Schedule for Clinical Assessment in Neuropsychiatry (SCAN),
      in a multiethnic sample of adult subjects with diabetes attending a diabetes
      center in Singapore. RESEARCH DESIGN AND METHODS: A total of 522 subjects (74.7%
      Chinese, 11.1% Malay, and 14.2% Indian) completed culturally adapted versions of
      the CES-D; 291 subjects were administered the SCAN inventory. RESULTS: The CES-D
      (cutoff score 16) showed high negative predictive values of more than 90% in all
      three ethnic groups. The prevalence of depressive symptoms (CES-D) and depression
      (SCAN) was significantly different between the Chinese and Indian subjects (CES-D
      27.4 vs. 43.2%, P = 0.006); (SCAN 15.0 vs. 31.1%, P = 0.01). CONCLUSIONS: The CES
      D proved to be a reliable instrument for identifying patients with depressive
      symptoms in the multiethnic setting of this study.

PMID- 18337304
TI  - Different cellular and molecular mechanisms for early and late-onset myelin
      protein zero mutations.
AB  - Mutations in the gene MPZ, encoding myelin protein zero (MPZ), cause inherited
      neuropathies collectively called Charcot-Marie-Tooth type 1B (CMT1B). Based on
      the age of onset, clinical and pathological features, most MPZ mutations are
      separable into two groups: one causing a severe, early-onset, demyelinating
      neuropathy and a second, causing a late-onset neuropathy with prominent axonal
      loss. To investigate potential pathomechanisms underlying the two phenotypes, we
      transiently transfected HeLa cells with two late-onset (T95M, H10P) and two early
      onset (H52R, S22_W28 deletion) mutations and analyzed their effects on
      intracellular protein trafficking, glycosylation, cell viability and
      intercellular adhesion. We found that the two late-onset mutations were both
      transported to the cell membrane and moderately reduced MPZ-mediated
      intercellular adhesion. The two early-onset mutations caused two distinct
      abnormalities. H52R was correctly glycosylated and trafficked to the plasma
      membrane, but strongly affected intercellular adhesion. When co-expressed with
      wild-type MPZ (wtMPZ), a functional dominant negative effect was observed.
      Alternatively, S22_W28 deletion was retained within the cytoplasm and reduced
      both adhesion caused by wtMPZ and cellular viability. Since the same trafficking
      patterns were observed in transfected murine Schwann cells, they are not an
      artifact of heterologous cell expression. Our results suggest that at least some
      late-onset mutations cause a partial loss of function in the transfected cells,
      whereas multiple abnormal gain of function pathways can result in early-onset
      neuropathy. Further characterization of these pathways will lead to a better
      understanding of the pathogenesis of CMT1B and a rational basis for treating
      these debilitating inherited neuropathies.

PMID- 18337305
TI  - New approach reveals CD28 and IFNG gene interaction in the susceptibility to
      cervical cancer.
AB  - Cervical cancer is a complex disease with multiple environmental and genetic
      determinants. In this study, we sought an association between polymorphisms in
      immune response genes and cervical cancer using both single-locus and multi-locus
      analysis approaches. A total of 14 single nucleotide polymorphisms (SNPs)
      distributed in CD28, CTLA4, ICOS, PDCD1, FAS, TNFA, IL6, IFNG, TGFB1 and IL10
      genes were determined in patients and healthy individuals from three independent
      case/control sets. The first two sets comprised White individuals (one group with
      82 cases and 85 controls, the other with 83 cases and 85 controls) and the third
      was constituted by non-white individuals (64 cases and 75 controls). The multi
      locus analysis revealed higher frequencies in cancer patients of three three
      genotype combinations [CD28+17(TT)/IFNG+874(AA)/TNFA-308(GG),
      CD28+17(TT)/IFN+847(AA)/PDCD1+7785(CT), and CD28
      +17(TT)/IFNG+874(AA)/ICOS+1564(TT)] (P < 0.01, Monte Carlo simulation). We
      hypothesized that this two-genotype [CD28(TT) and IFNG(AA)] combination could
      have a major contribution to the observed association. To address this question,
      we analyzed the frequency of the CD28(TT), IFNG(AA) genotype combination in the
      three groups combined, and observed its increase in patients (P = 0.0011 by
      Fisher's exact test). The contribution of a third polymorphism did not reach
      statistical significance (P = 0.1). Further analysis suggested that gene-gene
      interaction between CD28 and IFNG might contribute to susceptibility to cervical
      cancer. Our results showed an epistatic effect between CD28 and IFNG genes in
      susceptibility to cervical cancer, a finding that might be relevant for a better
      understanding of the disease pathogenesis. In addition, the novel analytical
      approach herein proposed might be useful for increasing the statistical power of
      future genome-wide multi-locus studies.

PMID- 18337306
TI  - A functionally dominant mitochondrial DNA mutation.
AB  - Mutations in mitochondrial DNA (mtDNA) tRNA genes can be considered functionally
      recessive because they result in a clinical or biochemical phenotype only when
      the percentage of mutant molecules exceeds a critical threshold value, in the
      range of 70-90%. We report a novel mtDNA mutation that contradicts this rule,
      since it caused a severe multisystem disorder and respiratory chain (RC)
      deficiency even at low levels of heteroplasmy. We studied a 13-year-old boy with
      clinical, radiological and biochemical evidence of a mitochondrial disorder. We
      detected a novel heteroplasmic C>T mutation at nucleotide 5545 of mtDNA, which
      was present at unusually low levels (<25%) in affected tissues. The pathogenic
      threshold for the mutation in cybrids was between 4 and 8%, implying a dominant
      mechanism of action. The mutation affects the central base of the anticodon
      triplet of tRNA(Trp) and it may alter the codon specificity of the affected tRNA.
      These findings introduce the concept of dominance in mitochondrial genetics and
      pose new diagnostic challenges, because such mutations may easily escape
      detection. Moreover, similar mutations arising stochastically and accumulating in
      a minority of mtDNA molecules during the aging process may severely impair RC
      function in cells.

PMID- 18337307
TI  - Biological effects of CCS in the absence of SOD1 enzyme activation: implications
      for disease in a mouse model for ALS.
AB  - The CCS copper chaperone is critical for maturation of Cu, Zn-superoxide
      dismutase (SOD1) through insertion of the copper co-factor and oxidization of an
      intra-subunit disulfide. The disulfide helps stabilize the SOD1 polypeptide,
      which can be particularly important in cases of amyotrophic lateral sclerosis
      (ALS) linked to misfolding of mutant SOD1. Surprisingly, however, over-expressed
      CCS was recently shown to greatly accelerate disease in a G93A SOD1 mouse model
      for ALS. Herein we show that disease in these G93A/CCS mice correlates with
      incomplete oxidation of the SOD1 disulfide. In the brain and spinal cord, CCS
      over-expression failed to enhance oxidation of the G93A SOD1 disulfide and if
      anything, effected some accumulation of disulfide-reduced SOD1. This effect was
      mirrored in culture with a C244,246S mutant of CCS that has the capacity to
      interact with SOD1 but can neither insert copper nor oxidize the disulfide. In
      spite of disulfide effects, there was no evidence for increased SOD1 aggregation.
      If anything, CCS over-expression prevented SOD1 misfolding in culture as
      monitored by detergent insolubility. This protection against SOD1 misfolding does
      not require SOD1 enzyme activation as the same effect was obtained with the
      C244,246S allele of CCS. In the G93A SOD1 mouse, CCS over-expression was likewise
      associated with a lack of obvious SOD1 misfolding marked by detergent
      insolubility. CCS over-expression accelerates SOD1-linked disease without the
      hallmarks of misfolding and aggregation seen in other mutant SOD1 models. These
      studies are the first to indicate biological effects of CCS in the absence of
      SOD1 enzymatic activation.

PMID- 18337308
TI  - Effects of gastric distension on the cardiovascular system in rainbow trout
      (Oncorhynchus mykiss).
AB  - When animals feed, blood flow to the gastrointestinal tract increases to ensure
      an adequate oxygen supply to the gastrointestinal tissue and an effective
      absorption of nutrients. In mammals, this increase depends on the chemical
      properties of the food, as well as, to some extent, on the mechanical distension
      of the stomach wall. By using an inflatable nitrile balloon positioned in the
      stomach, we investigated the cardiovascular responses to mechanical stretch of
      the stomach wall in rainbow trout (Oncorhynchus mykiss). Distension with a volume
      equivalent to a meal of 2% of the body mass increased dorsal aortic blood
      pressure by up to 29%, and central venous blood pressure increased transiently
      nearly fivefold. The increase in arterial pressure was mediated by an increased
      vascular resistance of both the systemic and the intestinal circulation. Cardiac
      output, heart rate, and stroke volume (SV) did not change, and only transient
      changes in gut blood flow were observed. The increase in arterial pressure was
      abolished by the alpha-adrenergic antagonist prazosin, indicating an active
      adrenergic vasoconstriction, whereas the venous pressor response could be the
      consequence of a passive increase in intraperitoneal pressure. Our results show
      that mechanical distension of the stomach causes an instantaneous increase in
      general vascular resistance, which may facilitate a redistribution of blood to
      the gastrointestinal tract when chemical stimuli from a meal induce vasodilation
      in the gut circulation. The normal postprandial increase in gut blood flow in
      teleosts is, therefore, most likely partly dependent on mechanical stimuli, as
      well as on chemical stimuli.

PMID- 18337309
TI  - Deleterious effects of endogenous and exogenous testosterone on mesenchymal stem
      cell VEGF production.
AB  - Modulating the paracrine effects of bone marrow mesenchymal stem cells (BMSCs)
      may be important for the treatment of ischemic myocardial tissue. In this regard,
      endogenous estrogen may enhance BMSC vascular endothelial growth factor (VEGF)
      production. However, little information exists regarding the effect of
      testosterone on stem cell function. We hypothesized that 1) endogenous or
      exogenous estrogen will enhance stem cell production of VEGF and 2) endogenous or
      exogenous testosterone will inhibit BMSC VEGF production. BMSCs were collected
      from adult male, female, castrated male, and ovariectomized female rats. One
      hundred thousand cells were incubated with testosterone (1, 10, or 100 nM) or
      estrogen (0.15, 1.5, or 15 nM) for 48 h. Cell supernatants were collected, and
      VEGF was measured by ELISA. BMSCs harvested from castrated males, normal females,
      and ovariectomized females produced more VEGF compared with normal males.
      Castration was associated with the highest level (1,018 +/- 98.26 pg/ml) of VEGF
      production by BMSCs, which was significantly more than that produced by BMSCs
      harvested from normal male and normal female animals. Exogenous testosterone
      significantly reduced VEGF production in BMSCs harvested from ovariectomized
      females in a dose-dependent manner. Exogenous estrogen did not alter BMSC VEGF
      production. These findings suggest that testosterone may work on BMSCs to
      decrease protective growth factor production and that effective removal of
      testosterone's deleterious effects via castration may prove to be beneficial in
      terms of protective factor production. By manipulating the mechanisms that BMSCs
      use to produce growth factors, we may be able to engineer stem cells to produce
      maximum growth factors during therapeutic use.

PMID- 18337310
TI  - Restraint increases afebrile body temperature but attenuates fever in Pekin ducks
      (Anas platyrhynchos).
AB  - In mammals, procedures such as handling, restraint, or exposure to open spaces
      induces an increase in body temperature (T(b)). The increase in temperature
      shares some characteristics with pyrogen-induced fever and so is often called
      "stress fever." Birds also respond to acute handling with a stress fever, which
      may confound thermoregulatory studies that involve animal restraint. We have
      measured the T(b) responses of Pekin ducks on days when they were restrained and
      compared them to days when the birds remained unrestrained. Restraint induced a
      0.5 degrees C increase in T(b) that was sustained for the entire 8 h of
      restraint. To determine whether the restraint-induced increase in T(b) is
      mediated by prostaglandins (PGs) we compared the T(b) responses during restraint
      after intraperitoneal injection with saline to the responses during restraint
      after injection with diclofenac sodium (15 mg/kg). There was no difference in
      response, suggesting that restraint affects T(b) by a PG-independent mechanism.
      We also compared the T(b) response to intramuscular injection of
      lipopolysaccharide (LPS; 100 microg/kg), a bacterial pyrogen, when the ducks were
      restrained or unrestrained. Despite T(b) being higher at the time of LPS
      injection when the ducks were restrained, the maximum temperature reached after
      LPS injection was higher, and the period that T(b) remained elevated was longer
      when the ducks were unrestrained. We conclude that restraint should be considered
      as a potential confounder in thermoregulatory studies in birds and presumably
      other species too.

PMID- 18337311
TI  - Volume expansion stimulates monoubiquitination and endocytosis of surface
      expressed skate anion-exchanger isoform.
AB  - In hyposmotic medium, skate erythrocytes swell and then lose taurine and other
      solutes with obligate water to achieve a regulatory volume decrease (RVD) over a
      90-min period. The skate erythrocyte anion-exchanger isoform 1 (skAE1)
      participates in the RVD, and increased surface expression after hyposmolality
      induced volume expansion occurs within 5 min but decreases to baseline within 120
      min. The subsequent fate of skAE1 is the focus of these studies. SkAE1 sent to
      the surface becomes monoubiquitinated, a modification that is present while skAE1
      is associated with clathrin and Rab5 but is removed before skAE1 is passed to the
      Rab4 compartment. Endocytosis of skAE1 involves clathrin-mediated
      internalization. Surface plasma membrane skAE1 forms tetramers and demonstrates
      increased tyrosine phosphorylation, and both of these processes decrease before
      skAE1 appears in the Rab5 compartment. Volume expansion-stimulated surface skAE1
      comes from an intracellular pool in a buoyant membrane fraction resistant to
      nonionic detergent extraction (DRM), and the amount of skAE1 increases in this
      buoyant DRM fraction on the surface. Clathrin heavy chain is found largely in the
      erythrocyte DRM, but in dense, rather than buoyant, fractions. Rab5- and Rab4
      containing membranes are largely detergent soluble, suggesting that as skAE1 is
      passed to clathrin and then to Rab5 compartments, the membrane microdomain
      composition changes. The present studies demonstrate that skAE1, which appears on
      the surface after hyposmolality-induced volume expansion, is monoubiquitinated, a
      modification that may serve as a signal for removal of skAE1 from the surface.
      This modification is eliminated after clathrin-mediated removal of skAE1 in a
      membrane domain containing Rab5, potentially permitting recycling and reuse of
      skAE1.

PMID- 18337312
TI  - Involvement of apical P2Y2 receptor-regulated CFTR activity in muscarinic
      stimulation of Cl(-) reabsorption in rat submandibular gland.
AB  - Previously, we presented in vivo evidence for a physiological significance of
      cAMP-regulated CFTR Cl(-) channels in Ca(2+)-activated Cl(-) reabsorption in the
      ductal system of the rat submandibular gland. Here, we address the mechanism by
      which basal CFTR activation contributes to the transepithelial Cl(-) movement
      evoked by muscarinic stimulation. The Cl(-) concentration ([Cl(-)]) was increased
      in the final saliva from rat submandibular gland during pilocarpine stimulation
      when a small interfering RNA for CFTR or a specific CFTR inhibitor, CFTR(inh)
      172, was injected retrogradely into the gland's own duct, indicating that basal
      CFTR activation is involved in Cl(-) reabsorption. Systemically administered
      propranolol failed to alter the [Cl(-)], suggesting little involvement of a beta
      adrenergic pathway in the Cl(-) movement that occurs through basal CFTR
      activation. Intraductal injection of suramin (a nonspecific P2-receptor
      antagonist) increased the salivary [Cl(-)], indicating the existence of
      endogenous purinergic activation. Upon separate intraductal injection, ATP and a
      P2Y(2)-receptor agonist, UTP, decreased the salivary [Cl(-)] almost equipotently.
      CFTR(inh)-172 and suramin each prevented these effects, whereas 2',3'-O-(4
      benzoylbenzoyl)-ATP (Bz-ATP), a P2X(7) agonist, had no specific effect.
      Pilocarpine stimulation evoked ATP secretion into the salivary fluid.
      Immunohistochemistry revealed the partial coexistence of CFTR and P2Y(2)
      receptors on the luminal surface of epithelial cells in the striated ducts of
      this gland. These results raise the possibility that muscarinic stimulation
      induced Cl(-) reabsorption occurs through basal CFTR activity and that this is
      regulated by P2Y(2) receptors in the ductal epithelium via stimulation by ATP
      secreted into the salivary fluid.

PMID- 18337313
TI  - Human heat balance during postexercise recovery: separating metabolic and
      nonthermal effects.
AB  - Previous studies report greater postexercise heat loss responses during active
      recovery relative to inactive recovery despite similar core temperatures between
      conditions. Differences have been ascribed to nonthermal factors influencing heat
      loss response control since elevations in metabolism during active recovery are
      assumed to be insufficient to change core temperature and modify heat loss
      responses. However, from a heat balance perspective, different rates of total
      heat loss with corresponding rates of metabolism are possible at any core
      temperature. Seven male volunteers cycled at 75% of Vo(2peak) in the Snellen
      whole body air calorimeter regulated at 25.0 degrees C, 30% relative humidity
      (RH), for 15 min followed by 30 min of active (AR) or inactive (IR) recovery.
      Relative to IR, a greater rate of metabolic heat production (M - W) during AR was
      paralleled by a greater rate of total heat loss (H(L)) and a greater local sweat
      rate, despite similar esophageal temperatures between conditions. At end
      recovery, rate of body heat storage, that is, [(M - W) - H(L)] approached zero
      similarly in both conditions, with M - W and H(L) elevated during AR by 91 +/- 26
      W and 93 +/- 25 W, respectively. Despite a higher M - W during AR, change in body
      heat content from calorimetry was similar between conditions due to a slower
      relative decrease in H(L) during AR, suggesting an influence of nonthermal
      factors. In conclusion, different levels of heat loss are possible at similar
      core temperatures during recovery modes of different metabolic rates. Evidence
      for nonthermal influences upon heat loss responses must therefore be sought after
      accounting for differences in heat production.

PMID- 18337314
TI  - Peripheral ghrelin treatment stabilizes body weights of senescent male Brown
      Norway rats at baseline and after surgery.
AB  - Unintentional weight loss may occur spontaneously in older humans and animals.
      Further weight losses after surgery or illness in the older patients result in
      increased morbidity, mortality, and hospital readmission rate. A growing body of
      work has shown increased appetite and weight gain in response to administration
      of ghrelin, the "hunger hormone." We conducted two studies in senescent male
      Brown Norway rats to assess the ability of peripheral administration of ghrelin
      to increase body weight and food intake. One study assessed the effect of 2 wk of
      daily subcutaneous ghrelin administration (1 mg.kg(-1).day(-1)) to senescent rats
      in a baseline condition; a second study used the same administration protocol in
      an interventional experiment with aged rats subjected to a surgery with 10-15%
      blood loss as a model of elective surgery. In both studies, animals receiving
      ghrelin maintained their body weights, whereas control animals lost weight. Body
      weight stability was achieved in ghrelin-treated animals despite a lack of
      increase in daily or cumulative food intake in both experiments. Hormone and
      proinflammatory cytokine levels were measured before surgery and after 14 days of
      treatment. Ghrelin treatment appeared to blunt declining ghrelin levels and also
      to blunt cytokine increases seen in the surgical control group. The ability of
      peripheral ghrelin treatment to maintain body weights of senescent rats without
      concomitant increases in food intake may be due to its known ability to decrease
      sympathetic activity and metabolic rate, perhaps by limiting cytokine-driven
      inflammation.

PMID- 18337315
TI  - Role of serotonergic input to the ventrolateral medulla in expression of the 10
      Hz sympathetic nerve rhythm.
AB  - We studied the changes in inferior cardiac sympathetic nerve discharge (SND)
      produced by unilateral microinjections of 5-hydroxytryptamine (5-HT) receptor
      agonists and antagonists into the ventrolateral medulla (VLM) of urethane
      anesthetized, baroreceptor-denervated cats. Microinjection of the 5-HT2 receptor
      antagonist LY-53857 (10 mM) into either the rostral or caudal VLM significantly
      reduced (P < or = 0.05) the 10-Hz rhythmic component of basal SND without
      affecting its lower-frequency, aperiodic component. The selective depression of
      10-Hz power was accompanied by a statistically significant decrease in mean
      arterial pressure (MAP). Microinjection of LY-53857 into the VLM also attenuated
      the increase in 10-Hz power that followed tetanic stimulation of depressor sites
      in the caudal medullary raphe nuclei. Microinjection of the 5-HT2 receptor
      agonist 1-(2,5-dimethoxy-4-iodophenyl)2-amino-propane (DOI; 10 microM) into the
      VLM selectively enhanced 10-Hz SND, and intravenous DOI (1 mg/kg) partially
      reversed the reduction in 10-Hz SND produced by 5-HT2 receptor blockade in the
      VLM. Microinjection of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n
      propylamino)tetralin (8-OHDPAT; 10 mM), into either the rostral or caudal VLM
      also selectively attenuated 10-Hz SND and significantly reduced MAP. The
      reduction in 10-Hz SND produced by 8-OHDPAT was partially reversed by intravenous
      WAY-100635 (1 mg/kg), which selectively blocks 5-HT1A receptors. These results
      support the view that serotonergic inputs to the VLM play an important role in
      expression of the 10-Hz rhythm in SND.

PMID- 18337317
TI  - Association of overactive bladder and stress urinary incontinence in rats with
      pudendal nerve ligation injury.
AB  - Approximately one-third of patients with stress urinary incontinence (SUI) also
      suffer from urgency incontinence, which is one of the major symptoms of
      overactive bladder (OAB) syndrome. Pudendal nerve injury has been recognized as a
      possible cause for both SUI and OAB. Therefore, we investigated the effects of
      pudendal nerve ligation (PNL) on bladder function and urinary continence in
      female Sprague-Dawley rats. Conscious cystometry with or without capsaicin
      pretreatment (125 mg/kg sc), leak point pressures (LPPs), contractile responses
      of bladder muscle strips to carbachol or phenylephrine, and levels of nerve
      growth factor (NGF) protein and mRNA in the bladder were compared in sham and PNL
      rats 4 wk after the injury. Urinary frequency detected by a reduction in
      intercontraction intervals and voided volume was observed in PNL rats compared
      with sham rats, but it was not seen in PNL rats with capsaicin pretreatment that
      desensitizes C-fiber-afferent pathways. LPPs in PNL rats were significantly
      decreased compared with sham rats. The contractile responses of detrusor muscle
      strips to phenylephrine, but not to carbachol, were significantly increased in
      PNL rats. The levels of NGF protein and mRNA in the bladder of PNL rats were
      significantly increased compared with sham rats. These results suggest that
      pudendal nerve neuropathy induced by PNL may be one of the potential risk factors
      for OAB, as well as SUI. Somato-visceral cross sensitization between somatic
      (pudendal) and visceral (bladder) sensory pathways that increases NGF expression
      and alpha(1)-adrenoceptor-mediated contractility in the bladder may be involved
      in this pathophysiological mechanism.

PMID- 18337316
TI  - TRPV1-mediated protection against endotoxin-induced hypotension and mortality in
      rats.
AB  - This study was designed to test the hypothesis that the transient receptor
      potential vanilloid type 1 (TRPV1) channel, expressed primarily in sensory
      nerves, and substance P (SP), released by sensory nerves, play a protective role
      against lipopolysaccharide (LPS)-induced hypotension. LPS (10 mg/kg iv) elicited
      tachycardia and hypotension in anesthetized male Wistar rats, which peaked at 10
      min and gradually recovered 1 h after the injection. Blockade of TRPV1 with its
      selective antagonist capsazepine (CAPZ, 3 mg/kg iv) impaired recovery given that
      the fall in mean arterial pressure (MAP) was greater 1 h after CAPZ plus LPS
      injections compared with LPS injection alone (45 +/- 5 vs. 25 +/- 4 mmHg, P <
      0.05). Blockade of the neurokinin 1 (NK1) receptor with its selective antagonists
      RP-67580 (5 mg/kg iv) or L-733,060 (4 mg/kg iv) prevented recovery, considering
      that falls in MAP were not different 1 h after injections of NK1 antagonists plus
      LPS from their peak decreases (66 +/- 9 vs. 74 +/- 5 mmHg or 60 +/- 7 vs. 69 +/-
      3 mmHg, respectively, P > 0.05). LPS increased plasma SP, norepinephrine (NE),
      and epinephrine (Epi) levels compared with vehicles, and the increases in plasma
      SP, NE, and Epi were significantly inhibited by CAPZ or RP-67580. The survival
      rate at 24 or 48 h after LPS injection (20 mg/kg ip) was lower in conscious rats
      pretreated with CAPZ or RP-67580 compared with rats treated with LPS alone (P <
      0.05). Thus our results show that the TRPV1, possibly via triggering release of
      SP which activates the NK1 and stimulates the sympathetic axis, plays a
      protective role against endotoxin-induced hypotension and mortality, suggesting
      that TRPV1 receptors are essential in protecting vital organ perfusion and
      survival during the endotoxic condition.

PMID- 18337318
TI  - The standardized development method of the Japanese guidelines for cancer
      screening.
AB  - BACKGROUND: To reduce cancer mortality, effective screening should be implemented
      properly. In Japan, the Research Group for Cancer Screening developed screening
      guidelines; however, the development process was not well established. METHODS:
      Based on the development processes of other guidelines, an original method,
      unique to Japan, was established to develop the Japanese cancer screening
      guidelines. RESULTS: The guideline development process involved the following
      steps: topic selection, development of the analytic framework, systematic
      literature review, translation to recommendations, consultation and publication.
      Mortality reduction related to cancer screening was evaluated using both direct
      and indirect evidence. To select appropriate articles, an analytic framework for
      cancer screening program with key questions was developed. Direct evidence was
      defined as a single body of evidence that established the linkage between
      screening and health outcomes such as mortality and incidence. The use of
      indirect evidence to determine the level of evidence was limited to situations
      where test accuracy could be compared with that of a method whose evidence was
      supported by randomized, controlled trials. Eight levels of evidence were defined
      based on the study design and quality. The benefits of each screening modality
      were determined based on the level of evidence according to the results of the
      systematic review. Balancing the benefits and harms, five grades of
      recommendation were formulated for population-based and opportunistic screening.
      After organized consultations, three types of guidelines were published.
      CONCLUSION: We developed a unique, standardized method for developing cancer
      screening guidelines in Japan. Based on this process, previously developed cancer
      screening guidelines have been revised.

PMID- 18337319
TI  - Variation of clinical target volume definition among Japanese radiation
      oncologists in external beam radiotherapy for prostate cancer.
AB  - BACKGROUND: We investigated the interobserver variation in the prostate target
      volume and the trend toward the use of diagnostic computed tomography (CT) or
      magnetic resonance (MR) images for treatment planning. METHODS: Twenty-five
      radiation oncologists were asked to draw the external contour of the prostate on
      CT images (0.3 cm spacing) of a patient with localized prostate cancer. They also
      answered a questionnaire regarding the use of diagnostic CT or MR images for the
      contouring. RESULTS: Of the 25 physicians, 28% rarely or never referred to the
      diagnostic CT images. In contrast, the physicians tended to refer to the MR
      images more frequently. Approximately 50% of the physicians believed in the
      usefulness of contrast-enhanced images for the delineation of the prostate. As
      for the variation of the prostate contouring, the median craniocaudal prostate
      length was 36 mm (range, 21-54 mm), and the median prostate volume was 43.5 cm(3)
      (range, 23.8-98.3 cm(3)). The interobserver variability was not significant in
      the duration as a radiation oncologist, the board certification status as
      radiation oncologists, and the number of treatment plans developed for prostate
      cancer during the last 1 year. CONCLUSION: A wide variety of the definitions of
      the prostate was found among Japanese radiation oncologists.

PMID- 18337320
TI  - A case of primary malignant melanoma of the esophagus.

PMID- 18337321
TI  - Comparison of time trends in skin cancer incidence (1973-97) in East Asia, Europe
      and USA, from Cancer Incidence in Five Continents Vol. IV-VIII.

PMID- 18337322
TI  - High frequency of early colorectal cancer in inflammatory bowel disease.
AB  - BACKGROUND AND AIMS: To detect precancerous dysplasia or asymptomatic cancer,
      patients suffering from inflammatory bowel disease often undergo colonoscopic
      surveillance based on American or British guidelines. It is recommended that
      surveillance is initiated after 8-10 years of extensive colitis, or after 15-20
      years for left-sided disease. These starting points, however, are not based on
      solid scientific evidence. Our aim was to assess the time interval between onset
      of inflammatory bowel disease (IBD) and colorectal carcinoma (CRC), and
      subsequently evaluate how many patients developed cancer before their
      surveillance was recommended to commence. METHODS: A nationwide automated
      pathology database (PALGA) was consulted to identify patients with IBD-associated
      colorectal carcinoma in seven university medical centres in The Netherlands
      between January 1990 and June 2006. Data were collected retrospectively from
      patient charts. Time intervals between onset of disease and cancer diagnosis were
      calculated in months. RESULTS: 149 patients were identified with confirmed
      diagnoses of IBD and CRC (ulcerative colitis n = 89/Crohn's disease n =
      59/indeterminate colitis n = 1). Taking date of diagnosis as the entry point, 22%
      of patients developed cancer before the 8 or 15 year starting points of
      surveillance, and 28% if surveillance was commenced 10 or 20 years after
      diagnosis for extensive or left-sided disease, respectively. Using onset of
      symptoms to calculate the time interval, 17-22% of patients would present with
      cancer prior to the surveillance starting points. CONCLUSIONS: These results show
      that the diagnosis of colorectal cancer is delayed or missed in a substantial
      number of patients (17-28%) when conducting surveillance strictly according to
      formal guidelines.

PMID- 18337323
TI  - Excision of lipomatous hypertrophy of the interatrial septum via port-access.
AB  - We present the surgical resection and repair, using port-access, in a case of
      extensive lipomatous hypertrophy of the interatrial septum (IAS). There was
      tumourous lipomatous hypertrophy on the superior vena cava (SVC) - atrial
      junction close to the aortic root beside massive IAS hypertrophy. Resection of
      involved IAS and SVC was performed using bovine pericardium for the repair.

PMID- 18337324
TI  - The revised International Health Regulations (2005): impact on yellow fever
      vaccination in clinical practice.

PMID- 18337325
TI  - Dengue and dengue hemorrhagic fever in northern Mexico and south Texas: do they
      really respect the border?

PMID- 18337326
TI  - Residual brain calcifications in neurocysticercosis.

PMID- 18337327
TI  - Epidemic dengue and dengue hemorrhagic fever at the Texas-Mexico border: results
      of a household-based seroepidemiologic survey, December 2005.
AB  - A dengue-2 epidemic causing dengue hemorrhagic fever (DHF) occurred in the
      contiguous border cities of Matamoros, Tamaulipas (Mexico), and Brownsville, TX,
      in 2005. In December, we conducted a household-based epidemiologic survey to
      determine the incidence and seroprevalence of dengue infection among Matamoros
      and Brownsville residents and to identify risk factors associated with infection.
      Antibodies to dengue were measured in 273 individuals. The estimated incidence of
      recent dengue infection was 32% and 4% among Matamoros and Brownsville
      participants, respectively. The estimated prevalence of past dengue infection was
      77% and 39% among Matamoros and Brownsville participants, respectively. The
      Breteau index was 28 in Matamoros and 16 in Brownsville, reflecting an abundant
      winter population of Aedes mosquitoes. Discarded waste tires and buckets were the
      two largest categories of infested containers found in both cities. Our results
      underscore the risk for epidemic dengue and DHF in the Texas-Mexico border
      region.

PMID- 18337328
TI  - Biochemical alterations as markers of dengue hemorrhagic fever.
AB  - We evaluated biochemical alterations as predictors of dengue hemorrhagic fever
      (DHF). Patients with confirmed infection with dengue virus were prospectively
      evaluated for the first seven days of disease to determine their final clinical
      outcome. Serum samples taken 48-96 hours after onset of fever were used for
      biochemical tests. Of 199 patients, 30 developed DHF. Cases of DHF had higher
      levels of lactate dehydrogenase (LDH), creatine kinase (CK), and aspartate
      aminotransferase, and lower levels of albumin, total cholesterol, and
      triglycerides. Multivariate analysis showed that early alterations of CK (hazard
      ratio [HR] = 6.98, 95% confidence interval [CI] = 2.34-20.85, P = 0.001), LDH (HR
      = 3.19, 95% CI = 1.01-10.12, P < 0.05), and albumin (HR = 2.54, 95% CI = 1.09
      5.92, P = 0.03) were associated with DHF. Triglyceride levels > 160 mg/dL were
      negatively associated with developing DHF (HR = 0.07, 95% CI = 0.01-0.59, P =
      0.01). Early alterations of biochemical markers can predict DHF in patients with
      acute fever caused by dengue.

PMID- 18337329
TI  - Anemia, iron deficiency, meat consumption, and hookworm infection in women of
      reproductive age in northwest Vietnam.
AB  - Iron deficiency anemia poses an important public health problem for women of
      reproductive age living in developing countries. We assessed the prevalence of
      iron deficiency and anemia and associated risk factors in a community-based
      sample of women living in a rural province of northwest Vietnam. A cross
      sectional survey, comprised of written questionnaires and laboratory analysis of
      hemoglobin (Hb), ferritin, transferrin receptor, and stool hookworm egg count,
      was undertaken, and the soluble transferrin receptor/log ferritin index was
      calculated. Of 349 non-pregnant women, 37.53% were anemic (Hb < 12 g/dL), and
      23.10% were iron deficient (ferritin < 15 ng/L). Hookworm infection was present
      in 78.15% of women, although heavy infection was uncommon (6.29%). Iron
      deficiency was more prevalent in anemic than non-anemic women (38.21% versus
      14.08%, P < 0.001). Consumption of meat at least three times a week was more
      common in non-anemic women (51.15% versus 66.67%, P = 0.042). Mean ferritin was
      lower in anemic women (18.99 versus 35.66 ng/mL, P < 0.001). There was no
      evidence of a difference in prevalence (15.20% versus 17.23%, P = 0.629) or
      intensity (171.07 versus 129.93 eggs/g, P = 0.412) of hookworm infection between
      anemic and non-anemic women. Although intensity of hookworm infection and meat
      consumption were associated with indices of iron deficiency in a multiple
      regression model, their relationship with hemoglobin was not significant. Anemia,
      iron deficiency, and hookworm infection were prevalent in this population. Intake
      of meat was more clearly associated with hemoglobin and iron indices than
      hookworm. An approach to addressing iron deficiency in this population should
      emphasize both iron supplementation and deworming.

PMID- 18337330
TI  - Difficulties in bringing point-of-use water treatment to scale in rural
      Guatemala.
AB  - In an earlier study in rural Guatemala, 257 households that received flocculant
      disinfectant to treat their drinking water had 39% less diarrhea than 257 control
      households. Three weeks after completion of the study, national marketing of the
      flocculant-disinfectant was extended into the study communities. Six months
      later, we assessed frequency of and characteristics associated with purchase and
      use of the flocculant-disinfectant by revisiting the original study households
      and administering a questionnaire. Four hundred sixty-two households (90%)
      completed the follow-up survey; 22 households (5%) purchased the flocculant
      disinfectant within the preceding 2 weeks and used it within the last week.
      Neither being randomized to the intervention group during the efficacy study nor
      combined spending on laundry soap, toothpaste, and hand soap in the preceding
      week was associated with active repeat use. Even after efficacy was demonstrated
      within their community and an aggressive sophisticated marketing approach, few
      households purchased flocculant-disinfectant for point-of-use water treatment.

PMID- 18337331
TI  - A randomized controlled pilot study of artesunate versus triclabendazole for
      human fascioliasis in central Vietnam.
AB  - Human fascioliasis caused by Fasciola hepatica or Fasciola gigantica is an
      increasing global problem. The mainstay of current treatment is triclabendazole,
      but resistance in animals has been described, and it is not available in many
      countries. The antimalarial artesunate has an excellent safety profile, and there
      is increasing evidence of its efficacy against other parasites both in vitro and
      in vivo. We performed a study to investigate the usefulness of artesunate in
      symptomatic human fascioliasis; 100 patients were enrolled. Patients treated with
      artesunate were significantly more likely to be free of abdominal pain at
      hospital discharge (50/50 versus 44/50, P = 0.027, relative risk 1.14, 95%
      confidence interval 1.03-1.26), but the complete response rate at 3 months was
      lower than for patients treated with triclabendazole (38/50 versus 46/50, P =
      0.05, RR 0.83, 95% CI 0.69-0.98, artesunate versus triclabendazole). There may be
      a role for artesunate in fascioliasis.

PMID- 18337332
TI  - Nonmalarial acute undifferentiated fever in a rural hospital in central India:
      diagnostic uncertainty and overtreatment with antimalarial agents.
AB  - Nonmalarial acute undifferentiated fever (NMAUF) refers to a febrile illness with
      no indication of an organ-specific disease after diagnosis of malaria has been
      excluded. In developing countries, the empirical treatment of NMAUFs with
      antimalarial drugs continues even in the era of highly specific rapid diagnostic
      tests (RDTs) for malaria. We carried out a retrospective review of patients with
      fever admitted to a rural teaching hospital in central India. We categorized
      patients with NMAUF into different clinical syndromes and determined their
      demographic profile, inhospital course, and the pattern of antimalarial use. The
      study sample included 1,197 adult patients who were investigated for malaria;
      1,053 (88%) of them had NMAUF, and use of further diagnostics in this group was
      limited. Despite one or more negative tests for malaria, many patients (39.9%,
      95% CI 37.0-43.3) received antimalarial drugs. These results suggest a need for
      guidelines and training to improve empirical treatment of NMAUF.

PMID- 18337333
TI  - Could neurocysticercosis be the cause of "onchocerciasis-associated" epileptic
      seizures?
AB  - We conducted a nodule prevalence survey in four onchocerciasis sentinel
      communities in Moyo and two in Kanungu districts of Uganda. Seven (33.3%) out of
      21 excised "onchocercomas" (nodules) in Moyo District and excised onchocercomas
      from four of six persons in Kanungu District turned out to be cysts of Taenia
      solium. We concluded that the prediction of nodule prevalence for noninvasive
      rapid epidemiologic assessment (REA) to target areas for mass chemotherapy with
      ivermectin in the African Program for Onchocerciasis Control (APOC) supported
      areas may have been influenced by other pathologies. T. solium infection may be
      the main cause of "onchocerciasis-associated epileptic seizures" in many
      onchocerciasis endemic communities that have been causally linked to
      onchocerciasis. Lastly, widespread neurocysticercosis may be a concern in mass
      treatment programs that provide praziquantel (for managing schistosomiasis) or
      albendazole (for managing intestinal worms or lymphatic filariasis) because these
      drugs may kill cerebral cysticerci, resulting in severe adverse events.

PMID- 18337334
TI  - Varicella zoster virus--specific immune response after treatment with sodium
      stibogluconate for cutaneous leishmaniasis.
AB  - Sodium stibogluconate has been associated with the reactivation of varicella
      zoster virus (VZV) in otherwise healthy adults who receive the drug as treatment
      for cutaneous leishmaniasis. Ten patients receiving daily sodium stibogluconate
      underwent phlebotomy at baseline and at day 10. Flow cytometry-based
      immunophenotyping, VZV-specific IgG levels, and lymphocyte proliferative
      responses and intracellular cytokine secretion to VZV, cytomegalovirus, tetanus
      toxoid, superantigen, and mitogens were performed at both time points. The
      absolute number of total leukocytes, total lymphocytes, and lymphocyte subsets
      decreased overall without predilection for any particular subset of lymphocytes,
      such that the percentage of the total lymphocyte population for each lymphocyte
      subset did not change significantly (except for a marginal increase in percentage
      of cytotoxic T cells). Antibodies to VZV were measured in seven patients before
      and after treatment, and did not change. Lymphocyte proliferative responses to
      VZV and other antigens and mitogens did not change from baseline. The mechanism
      for the increased rate of VZV reactivation after treatment with sodium
      stibogluconate remains undefined.

PMID- 18337335
TI  - A case of erysipeloid cutaneous leishmaniasis: atypical and unusual clinical
      variant.
AB  - Cutaneous leishmaniasis has a number of morphologic variants such as acute
      paronychial, chancriform, annular, palmoplantar, zosteriform, and eczematoid,
      which depend on the immune condition of the patients, the subspecies of the
      Leishmania, and the area of the localization. In recent times, the number of
      reports of new and rare variants of cutaneous leishmaniasis has been increasing.
      In this report, we describe a very rare variant of Cutaneous leishmaniasis,
      presented with ulceration on glabellar region and infiltrative erythematous
      lesions covering the center of the face, resembling erysipelas.

PMID- 18337336
TI  - Intestinal parasites in Kaposi sarcoma patients in Uganda: indication of shared
      risk factors or etiologic association.
AB  - Kaposi sarcoma (KS) is endemic in Uganda and shares several risk factors with
      intestinal parasite infestation, including rural residence, contact with surface
      water, and walking barefoot, however, the significance of these ecologic
      relationships is unknown. We investigated these relationships among 1,985 Ugandan
      patients with cancer. Odds ratios (OR) were calculated using logistic regression.
      KS patients had higher carriage of Strongyloides stercoralis larvae (OR 2.1, 95%
      CI 1.2-3.7) and lower carriage of hookworm ova (0.6, 0.4-1.0) and Entamoeba coli
      cysts (0.7, 0.5-1.0), after adjusting for region of residence, age, gender, and
      diagnosis. While our findings may be due to confounding, they are compatible with
      shared risk factors or etiological association between parasites and KS, and
      warrant well-designed follow up studies.

PMID- 18337337
TI  - Vector competence of eastern and western forms of Psorophora columbiae (Diptera:
      Culicidae) mosquitoes for enzootic and epizootic Venezuelan equine encephalitis
      virus.
AB  - Venezuelan equine encephalitis virus (VEEV) continues to circulate enzootically
      in Mexico with the potential to re-emerge and cause disease in equines and humans
      in North America. We infected two geographically distinct mosquito populations of
      eastern Psorophora columbiae form columbiae (Chiapas, Mexico and Texas, United
      States) and one mosquito population of western Psorophora columbiae form toltecum
      (California, United States) with epizootic and enzootic IE VEEV and epizootic IAB
      VEEV. We detected no differences between epizootic and enzootic IE viruses in
      their ability to infect any of the mosquito populations analyzed, which suggested
      that neither species selects for epizootic IE viruses. Psorophora columbiae f.
      columbiae (Texas) were significantly less susceptible to infection by epizootic
      IE than Ps. columbiae f. columbiae (Mexico). Psorophora columbiae f. toltecum
      populations were more susceptible than Ps. columbiae f. columbiae populations to
      epizootic IE and IAB viruses.

PMID- 18337338
TI  - Susceptibility of Florida mosquitoes to infection with chikungunya virus.
AB  - Chikungunya virus (CHIKV) has caused recent, large epidemics on islands in the
      Indian Ocean, raising the possibility of more widespread CHIKV epidemics.
      Historically, CHIKV has been vectored by Aedes aegypti, but these outbreaks
      likely also involved Ae. albopictus. To examine the potential for an outbreak of
      CHIKV in Florida, we determined the susceptibility to CHIKV of F1 Ae. aegypti and
      Ae. albopictus from Florida. In addition, we also evaluated two well
      characterized laboratory strains (Rockefeller and Lake Charles) of these species.
      We determined infection and dissemination rates as well as total body titer of
      mosquitoes 7 days post-exposure (pe) (Ae. albopictus) and 3, 7, and 10 days pe
      (Ae. aegypti). All mosquito strains were susceptible to both infection and
      dissemination, with some variation between strains. Our results suggest Florida
      would be vulnerable to transmission of CHIKV in urban and rural areas where the
      two vector species occur.

PMID- 18337339
TI  - Safety and immunogenicity of a tetravalent live-attenuated dengue vaccine in
      flavivirus naive children.
AB  - A live-attenuated tetravalent dengue virus (DENV) vaccine candidate has been well
      tolerated and immunogenic in healthy, US flavivirus naive adult volunteers. We
      conducted a pilot, safety, and immunogenicity trial of the vaccine candidate in
      healthy Thai children (6-7 years of age) to prepare for its eventual evaluation
      in Thai infants. In an uncontrolled, open clinical trial, the investigational
      vaccine was administered on study Days 0 and 180 to seven volunteers residing in
      Bangkok without neutralizing antibodies to DENV1-4 or to Japanese encephalitis
      virus (JEV). Clinical and laboratory safety assessments were completed during the
      30 days after each vaccine dose, and immunogenicity was determined at Day 30. In
      this study, the vaccine was well tolerated with no serious adverse events or
      alert laboratory values. One volunteer experienced fever (38.2 degrees C, < 2
      days) and associated DENV4 vaccine viremia 7 days after Dose 2. One month after
      Dose 2, six volunteers in the per-protocol analysis exhibited a tetravalent
      neutralizing antibody response with DENV1-4 geometric mean titers of 55, 475,
      350, and 171, respectively. Ten weeks (~75 days) after Dose 2, five of the six
      volunteers continued to exhibit a tetravalent neutralizing antibody profile; one
      volunteer's DENV4 PRNT50 titer fell below the assay cut-off (29 --> < 10);
      (clinicaltrials.gov NCT00384670).

PMID- 18337340
TI  - Serologic diagnosis of West Nile and St. Louis encephalitis virus infections in
      domestic chickens.
AB  - Adult domestic chickens were infected with West Nile virus (WNV) or St. Louis
      encephalitis virus (SLEV) and challenged with homologous or heterologous virus at
      21 or 56 days postinfection (dpi). Sera were collected at selected time points
      after infection and assayed by enzyme immunoassay (EIA), plaque reduction
      neutralization test (PRNT), and a Western blot (WB) alternative to PRNT. EIA
      results were sensitive and accurate (few false positives) but not specific,
      requiring a confirmatory test to determine virus infection history. PRNT results
      generally were specific until challenge, after which test results were frequently
      equivocal and inadequate to determine first or second infecting virus. WB results
      confirmed the serologic cross-reactivity between WNV and SLEV envelope protein.
      Non-structural protein 1 and pre-membrane protein reactivities were highly
      specific for WNV during SLEV infection, but less specific for SLEV during WNV
      infection. WB and PRNT specificities were similar for both viruses from 6 to 14
      dpi, and sensitivities to WNV were virtually identical.

PMID- 18337341
TI  - Increased Plasmodium falciparum gametocyte production in mixed infections with P.
      malariae.
AB  - Plasmodium falciparum and P. malariae occur endemically in many parts of Africa.
      Observations from malariotherapy patients suggest that co-infection with P.
      malariae may increase P. falciparum gametocyte production. We determined P.
      falciparum gametocyte prevalence and density by quantitative nucleic acid
      sequence-based amplification (QT-NASBA) after antimalarial treatment of Kenyan
      children with either P. falciparum mono-infection or P. falciparum and P.
      malariae mixed infection. In addition, we analyzed the relationship between mixed
      species infections and microscopic P. falciparum gametocyte prevalence in three
      datasets from previously published studies. In Kenyan children, QT-NASBA
      gametocyte density was increased in mixed species infections (P = 0.03). We also
      observed higher microscopic prevalences of P. falciparum gametocytes in mixed
      species infections in studies from Tanzania and Kenya (odds ratio = 2.15, 95%
      confidence interval = 0.99-4.65 and 2.39, 1.58-3.63) but not in a study from
      Nigeria. These data suggest that co-infection with P. malariae is correlated with
      increased P. falciparum gametocytemia.

PMID- 18337342
TI  - Malaria in pregnancy in the Solomon islands: barriers to prevention and control.
AB  - A study of malaria in pregnancy (MIP) was undertaken in Marovo Lagoon, Solomon
      Islands, to evaluate pregnancy-specific control strategies for malaria.
      Peripheral parasitemia was present in 18% (19/106) of women: 15 Plasmodium
      falciparum and 4 P. vivax. Primigravidae were twice as likely to be parasitemic
      as multigravidae (31% versus 14%; relative risk: 2.24; 95% confidence interval:
      1.01-4.96; P = 0.05). Although ante-natal clinic attendance was high, women
      booked late (mean, 19.7 weeks) and attended irregularly. Free insecticide-treated
      nets (ITN) were not distributed despite government policy. Primigravidae were
      less likely to have an ITN in their homes than multigravidae (relative risk:
      2.13; 95% confidence interval: 1.03-4.40). Coverage with chloroquine prophylaxis
      was low. This study revealed barriers to control of MIP at both the health
      service and client level. To develop an evidence-based malaria control policy in
      pregnancy for this region, further study of the epidemiology of malaria and its
      effects, including social and behavioral aspects, is needed.

PMID- 18337343
TI  - Efficacy, safety, and selection of molecular markers of drug resistance by two
      ACTs in Mali.
AB  - We conducted a randomized single-blinded trial comparing the efficacy and safety
      of artesunate (AS) + amodiaquine (AQ, 3 days) versus AS (3 days) + sulfadoxine
      pyrimethamine (SP, single dose) versus AS monotherapy (5 days) in Southern Mali.
      Uncomplicated malaria cases were followed for 28 days. Molecular markers of drug
      resistance were determined. After identification of recrudescences by genotyping,
      both artemisinin-based combination therapies (ACTs) reached nearly 100% efficacy
      at Day 14 and Day 28 versus 98.3% and 96.5% for AS, respectively (P > 0.05). AS +
      SP significantly selected DHFR and DHPS mutations associated with sulfadoxine and
      pyrimethamine resistance (P < 0.001), and AS + AQ equally selected PfCRT and
      PfMDR1 point mutations associated with chloroquine and AQ resistance (P < 0.001).
      No significant adverse event attributable to any of the study drugs was found.
      The ACTs were efficacious and safe, but the selection of markers for resistance
      to the partner drugs raises concerns over their lifespan in areas of intense
      malaria transmission.

PMID- 18337344
TI  - Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and
      DHPS from malaria endemic areas of Thailand.
AB  - Both malaria treatment and prophylaxis target the parasite dihydropteroate
      synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes. Specific point
      mutations in these genes confer resistance to sulfadoxine-pyrimethamine (SP) in
      both Plasmodium falciparum and P. vivax. We used direct sequencing to examine the
      prevalence of point mutations in pvdhps and pvdhfr in 160 P. vivax isolates
      collected from areas along the international borders of Thailand. Results show
      that the majority of the isolates harbored a quadruple mutant allele of pvdhfr
      and a double mutant allele of pvdhps, but the distribution was not uniform. The
      highly mutant allele combination was especially prevalent along the Thai-Myanmar
      border, whereas the majority of the isolates from areas along the Thai-Cambodian
      and Thai-Malaysian borders carried double mutant alleles of pvdhfr and single
      mutant alleles of pvdhps. Novel mutations that have not been identified
      previously at codon 512 of pvdhps (K512M, K512E, K512T) were also found.

PMID- 18337345
TI  - Miniaturization of a high-throughput pLDH-based Plasmodium falciparum growth
      inhibition assay for small volume samples from preclinical and clinical vaccine
      trials.
AB  - To date, no immune correlates for blood stage-specific immunity against
      Plasmodium falciparum malaria parasites have been identified. Growth and/or
      invasion inhibition assays using sera from Phase 2a/b trials will aid in
      determining whether correlations with protective immunity can be established for
      these assays. A major constraint in the ability to evaluate functional antibody
      activities from populations in endemic areas is the relatively limited
      availability of sufficient sample quantity. For this reason, we developed a
      miniaturized and high-throughput method to measure growth inhibitory activity by
      quantification of parasite lactate dehydrogenase (pLDH) in a 384-microtiter plate
      format. This culture method can be extended beyond the pLDH-based readout to
      other techniques commonly used to determine growth/invasion inhibition.

PMID- 18337346
TI  - Two Triatoma dimidiata clades (Chagas disease vector) associated with different
      habitats in southern Mexico and Central America.
AB  - Triatoma dimidiata is the only reported Chagas disease vector in Campeche,
      Mexico. The purpose of this study was to determine the genetic variability of
      vectors from Campeche coastal and rain forest areas and establish a phylogenetic
      relationship with other T. dimidiata populations by analyzing the internal
      transcribed spacer-2 (ITS-2) region. The sequence length of samples from Campeche
      ranged from 469 to 478 basepairs. The ITS-2 variability among the populations
      enabled us to classify them into two clades with an 18-22 nucleotide difference.
      The genetic distance (0.042) between them confirms this divergence. Phylogenetic
      analysis of gene genealogies confirmed these two clades. Furthermore, the
      population genetic analyses showed two groups with little genetic similarity or
      migration between them. One group was associated with the tropical forest area
      and the other group was associated with a mainly coastal distribution. This
      correlation was also observed when T. dimidiata from other regions of Mexico and
      Central America were analyzed.

PMID- 18337347
TI  - Genetic relationships among Aedes aegypti collections in Venezuela as determined
      by mitochondrial DNA variation and nuclear single nucleotide polymorphisms.
AB  - A population genetic analysis of gene flow was conducted among 619 Aedes aegypti
      from nine collections distributed among six geographic regions of Venezuela.
      Genetic markers included a 387-basepair region of the mitochondrial NADH
      dehydrogenase 4 (ND4) gene and single nucleotide polymorphisms (SNPs) at 11
      nuclear loci. Genotypes at SNP loci were identified using melting curve analysis.
      Six different ND4 haplotypes were detected and patterns of variation suggested
      that collections were isolated by distance. The variance in SNP allele
      frequencies was much less than the variance in haplotype frequencies and a
      pattern of isolation by distance was not detected. Aedes aegypti from eight
      collections were orally challenged with dengue 2 virus. Disseminated infection
      rates ranged from 77% to 95%. The percentage of mosquitoes exhibiting a midgut
      infection barrier ranged from 2% to 15%, and those exhibiting a midgut escape
      barrier ranged from 2% to 18%. Venezuelan Ae. aegypti appear to be susceptible to
      dengue virus infection.

PMID- 18337348
TI  - Improved molecular technique for the differentiation of neotropical anopheline
      species.
AB  - We evaluated a PCR-RFLP of the ribosomal internal transcribed spacer 2 region
      (ITS2) to distinguish species of Anopheles commonly reported in the Amazon and
      validated this method using reared F1 offspring. The following species of
      Anopheles were used for molecular analysis: An. (Nys.) benarrochi, An. (Nys.)
      darlingi, An. (Nys.) nuneztovari, An. (Nys.) konderi, An. (Nys.) rangeli, and An.
      (Nys.) triannulatus sensu lato (s.l.). In addition, three species of the subgenus
      Anopheles, An. (Ano.) forattini, An. (Ano.) mattogrossensis, and An. (Ano.)
      peryassui were included for testing. Each of the nine species tested yielded
      diagnostic banding patterns. The PCR-RFLP method was successful in identifying
      all life stages including exuviae with small fractions of the sample. The assay
      is rapid and can be applied as an unbiased confirmatory method for identification
      of morphologic variants, disputed samples, imperfectly preserved specimens, and
      life stages from which taxonomic keys do not allow for definitive species
      determination.

PMID- 18337349
TI  - Soluble tumor necrosis factor (TNF) receptors (sTNF-R1 and -R2) in pregnant women
      chronically infected with Trypanosoma cruzi and their children.
AB  - Most congenital transmissions of Trypanosoma cruzi are not detected. As the
      levels of mediators regulating the immune response might be different in the
      absence or in the presence of transmission, we explored the levels of tumor
      necrosis factor (TNF) and soluble TNF receptors TNF-R1 and -R2 in T. cruzi
      infected pregnant women and the neonates. We previously found that the
      circulating levels of TNF were higher in non-transmitting than in transmitting
      pregnant women. This observation has now been extended to the spontaneous release
      of TNF by peripheral blood leukocytes (PBLs) that was also higher in non
      transmitting than in transmitting pregnant women. As their mothers, non-infected
      neonates had higher circulating levels of TNF than congenitally infected
      children. The circulating levels of sTNF-R1 increased in non-transmitting and
      transmitting mothers and in infected and non-infected neonates. The circulating
      levels of sTNF-R2 were approximately 60% higher in infected than in non-infected
      neonates (1,635 +/- 101 and 1,027 +/- 100 pg/mL, respectively) and remained
      higher at 1 year of age. This important increase, only observed in infected
      neonates, could be useful to orientate to the presence of vertical transmission
      of T. cruzi infection.

PMID- 18337350
TI  - Prevalence of infection with Toxoplasma gondii among pregnant women in Cali,
      Colombia, South America.
AB  - The aim of this study was to determine the prevalence of toxoplasma antibodies
      among pregnant women in Cali, Colombia. In 2005, 955 pregnant women were tested
      for IgG and IgM antibodies and sociodemographic information was collected. Their
      average age was 25.1 years, overall IgG seroprevalence 45.8% (95% CI: 41.8%,
      48.2%), IgM 2.8% (95% CI: 1.5%, 3.6%). Seroprevalence increased significantly
      with age, 39.0% in 14 to 19 years to 55.3% in 30 to 39 years (P = 0.001). There
      was a significant trend toward a higher seroprevalence in the lower socioeconomic
      strata (SES) (low: 49.0%, high: 29%, P = 0.004). The increase in seroprevalence
      by age was more significant in the lower socioeconomic strata (P = 0.002). Our
      results suggest a higher prevalence when compared with those of the national 1980
      (33-37.6%) survey. In contrast to reports from other regions of the world, Cali
      has not seen a decrease in T. gondii seroprevalence over the past 25 years.

PMID- 18337351
TI  - Rapid detection of Brugia malayi in mosquito vectors using a real-time
      fluorescence resonance energy transfer PCR and melting curve analysis.
AB  - We developed real-time fluorescence resonance energy transfer (FRET) polymerase
      chain reaction (PCR) combined with melting curve analysis for detection of Brugia
      malayi DNA in blood-fed mosquitoes. Real-time FRET PCR is based on a fluorescence
      melting curve analysis of hybrid formed between amplicons generated from a family
      of repeated DNA element, 153-bp HhaI repeated sequence, specific to genus Brugia
      and specific fluorophore-labeled probes. The B. malayi-infected mosquitoes were
      differentiated from Wuchereria bancrofti-infected and uninfected mosquitoes and
      from genomic DNA of Dirofilaria immitis--and Plasmodium falciparum--infected
      human red blood cells and human leukocytes by their melting temperature.
      Sensitivity and specificity were both 100%. Melting curve analysis produces a
      rapid, accurate, and sensitive alternative for specific detection of B. malayi in
      mosquitoes, allows high throughput, and can be performed on small samples. This
      method has the potential for endemic area mapping or monitoring effect of brugian
      filariasis mass treatment programs.

PMID- 18337352
TI  - The molecular epidemiology of ocular Chlamydia trachomatis infections in Western
      Australia: implications for trachoma control.
AB  - We studied the serovar distribution of Chlamydia trachomatis in patients with
      clinical eye disease in Western Australia. Most disease occurred in indigenous
      communities and was caused by trachoma serovars Ba and C. Serovar Ba was
      genetically homogeneous throughout Western Australia and identical to strains
      previously described in indigenous communities in Northern Territory. This
      finding probably results from movement of these populations, and suggests that a
      widely coordinated, rather than local or regional, approach is needed to control
      trachoma in mobile populations. Serovar C strains within Western Australia were
      homogeneous but distinct from those in Northern Territory, possibly because of
      inherent differences in transmissibility or differences in population movements
      among communities carrying the different serovars. Genital serovars were
      occasional causes of eye diseases in infants, adolescents, and adults in trachoma
      endemic areas. These serovars should be considered in the differential diagnosis
      of acute follicular conjunctivitis in these groups.

PMID- 18337353
TI  - Transmission of leprosy: a study of skin and nasal secretions of household
      contacts of leprosy patients using PCR.
AB  - It is generally held that dissemination of Mycobacterium leprae is from nasal
      mucosa and not through the skin of infected patients. In this study, we evaluated
      M. leprae in the unbroken skin and nasal secretions of multibacillary (MB)
      leprosy patients and their contacts. Specimens were examined by direct microscopy
      and polymerase chain reaction (PCR) for M. leprae DNA. Results showed that 60% of
      untreated MB leprosy patients examined histologically had acid-fast bacilli in
      the keratin layer. By PCR studies it was found that 80% of the patients had M.
      leprae DNA in skin washings and 60% had M. leprae DNA on swabs obtained from the
      nasal mucosa. Ninety-three contacts of the untreated MB cases were also tested
      for exposure to M. leprae by analyzing skin washings and nasal secretions by PCR.
      PCR analysis showed significant skin (17% positive) and nasal muscosal (4%)
      exposure in contacts before instituting treatment of the index cases. After 2
      months of treating the index cases, all contacts tested were negative for M.
      leprae DNA. These data suggested that both skin and nasal epithelia of untreated
      MB leprosy patients contribute to the shedding of M. leprae into the environment
      and contacts of untreated MB cases are at risk for contact with M. leprae through
      both the nasal mucosa and exposed surfaces of their skin.

PMID- 18337354
TI  - Detection and characterization of Human caliciviruses associated with sporadic
      acute diarrhea in adults in Djibouti (horn of Africa).
AB  - Recent advances in molecular diagnostics have allowed us to recognize Human
      caliciviruses (HuCVs) as important agents of acute diarrhea in industrialized
      countries. Their prevalence and genetic diversity in developing countries remains
      unknown. We report on the characterization of HuCVs among adults presenting acute
      diarrheas in Djibouti; 108 stool samples collected were screened by EIA, RTPCR,
      or cell cultures for the group A Rotaviruses, Adenoviruses, Astroviruses, and
      HuCVs, which were further characterized by genotyping. Among stool samples
      screened for HuCVs, 25.3% were positive. The other enteric viruses were less
      prevalent. The 11 HuCV strains sequenced revealed a large diversity (3
      sapoviruses and 8 noroviruses). GII strains noroviruses were predominant, five
      were newly described genotypes, and two were recombinant with a pol gene related
      to GGIIb strains with the particularity to associate a unique pol gene to
      different capsid genes. These results could help to the knowledge of HuCV
      infections in Tropical Africa.

PMID- 18337355
TI  - Rapid spread of Vibrio cholerae O1 throughout Kenya, 2005.
AB  - Between January and June 2005, 5 distinct cholera outbreaks occurred in Kenya.
      Overall, 990 cases and 25 deaths (2.5%) were reported. Four outbreaks occurred in
      towns along major highways, and 1 occurred in a refugee camp near the Sudanese
      border, accessible to Nairobi by daily flights. Matched case-control studies from
      2 outbreaks showed that failure to treat drinking water and storing drinking
      water in wide-mouthed containers were significantly associated with disease.
      Isolates from all 5 outbreaks were Vibrio cholerae O1, Inaba serotype, and had
      genetically similar PFGE patterns of SfiI-digested chromosomal DNA. Linkage of
      the outbreak locations by major transportation routes, their temporal proximity,
      and similar PFGE patterns of isolates suggests the outbreaks might have been
      linked epidemiologically, showing the speed and distance of cholera spread in
      countries like Kenya with pockets of susceptible populations connected by modern
      transportation. Prevention measures remain implementation of point-of-use safe
      water systems and case finding and referral.

PMID- 18337356
TI  - Control of Pteridium aquilinum: meta-analysis of a multi-site study in the UK.
AB  - BACKGROUND AND AIMS: A great deal of money is spent controlling invasive weeds as
      part of international and national policies. It is essential that the funded
      treatments work across the region in which the policies operate. We argue that
      experiments across multiple sites are required to validate these programs as
      results from single sites may be misleading. Here, the control of Pteridium
      aquilinum (bracken) is used as a test example to address the following four
      questions. (1) Does the effectiveness of P. aquilinum-control treatments vary
      across sites? (2) Is the best treatment identified in previous research (cutting
      twice per year) consistent at all sites, and if not why not? (3) Is treatment
      performance related to P. aquilinum rhizome mass, litter cover or litter depth at
      the various sites? (4) Does successful P. aquilinum control influence species
      richness? METHODS: Pteridium aquilinum-control treatments were monitored for 10
      years using six replicated experiments and analysed using meta-analysis. Meta
      regressions were used to explore heterogeneity between sites. KEY RESULTS: The
      effectiveness of treatments varied between sites depending on the measure used to
      assess P. aquilinum performance. In general, cutting twice per year was the most
      successful treatment but on some sites other, less expensive treatments were as
      good. The effectiveness of treatments at different sites was not related to
      rhizome mass, but the effectiveness of most applied treatments were inversely
      related to post-control litter. Effective treatment was also associated with high
      species richness. CONCLUSIONS: It is concluded that successful development of
      national weed control programs requires multi-site experimental approaches. Here,
      meta-analyses demonstrate that variation in effectiveness between sites could be
      explained in part by pre-specified variables. Reliance on data from a single site
      for policy formulation is therefore clearly dangerous.

PMID- 18337357
TI  - Magnetic resonance imaging and clinical evaluation of patellar resurfacing with
      press-fit osteochondral autograft plugs.
AB  - BACKGROUND: Autologous osteochondral transplantation (AOT) has been successfully
      used in the femoral condyle and trochlea and is an attractive treatment option
      for full-thickness patellar cartilage lesions. HYPOTHESIS: Patients treated with
      AOT for the repair of symptomatic, isolated patellar cartilage lesions will
      demonstrate improvement in functional outcomes and postoperative magnetic
      resonance imaging appearance. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Between 2002 and 2006, patients with focal patellar cartilage lesions
      treated with AOT were prospectively followed. The mean age at the time of surgery
      was 30 years. Clinical assessment was performed with the International Knee
      Documentation Committee (IKDC), activities of daily living of the Knee Outcome
      Survey (ADL), and Short Form-36 (SF-36) at baseline and most recent follow-up.
      Magnetic resonance imaging was used to evaluate the cartilage repair morphologic
      characteristics in 14 cases. RESULTS: Twenty-two patients met the study criteria
      with a mean follow-up of 28.7 months (range, 17.7-57.8 months). The mean patellar
      lesion size was 165.6 +/- 127.8 mm(2), and the mean size of the donor plug was
      9.7 +/- 1.1 mm in diameter with 1.8 +/- 1.4 plugs/defect. The mean preoperative
      IKDC score was 47.2 +/- 14.0 and improved to 74.4 +/- 12.3 (P = .028). The mean
      preoperative ADL score was 60.1 +/- 16.9 and increased to 84.7 +/- 8.3 (P =
      .022). The mean SF-36 also demonstrated an improvement, from 64.0 +/- 14.8 at
      baseline to 79.4 +/- 15.4 (P = .059). Nine patients underwent concomitant distal
      realignment and demonstrated improvement between preoperative and postoperative
      outcomes scores, but these differences were not statistically significant.
      Magnetic resonance imaging appearance demonstrated that all plugs demonstrated
      good (67%-100%) cartilage fill, 64% with fissures < 2 mm at the articular
      cartilage interface, 71% with complete trabecular incorporation, and 71% with
      flush plug appearance. CONCLUSION: Patellar AOT is an effective treatment for
      focal patellar chondral lesions, with significant improvement in clinical follow
      up. This study suggests that patients with patellar malalignment may represent a
      subset of patients who have a poor prognostic outlook compared with patients with
      normal alignment.

PMID- 18337358
TI  - Role of the vastus medialis obliquus in repositioning the patella: a dynamic
      computed tomography study.
AB  - BACKGROUND: It has been assumed that patellofemoral pain syndrome results from
      patellar malalignment. The precise role the vastus medialis obliquus plays in
      mediating the underlying pathologic abnormality is unclear. HYPOTHESIS: The
      morphologic characteristics of the vastus medialis obliquus correlate to patellar
      malalignment in patients with patellofemoral pain syndrome. STUDY DESIGN: Cross
      sectional study; Level of evidence, 3. METHODS: One hundred twelve patients with
      patellofemoral pain syndrome were studied. Six sets of computed tomography axial
      images were assessed in which knee flexion was 0 degrees, 15 degrees, or 30
      degrees and the quadriceps muscle either relaxed or contracted. Measurements of
      serial cross-sectional areas of the vastus medialis obliquus and patellar
      malalignment were made. Correlation and stepwise regression models between the
      vastus medialis obliquus variables and patellar malalignment (lateral shift and
      patellar tilt) were calculated. Statistics were calculated on 4 subgroups
      depending on patellofemoral malalignment type. RESULTS: Significant correlations
      were found between measures of cross-sectional areas of vastus medialis obliquus
      and patellar tilt at 0 degrees and 30 degrees of knee flexion. Using a regression
      model, it was determined that vastus medialis obliquus is predictive of patellar
      tilt (R(2) = 0.078-0.130). This explanation was most apparent in the subgroup of
      patients with extreme patellar tilt and lateral shift malalignments (R(2) up to
      0.824). CONCLUSION: There are significant correlations between vastus medialis
      obliquus variables and patellar malalignments in extended knees of patients with
      patellofemoral pain syndrome. CLINICAL RELEVANCE: Vastus medialis obliquus muscle
      function is important to consider in the rehabilitation of patients with
      patellofemoral pain syndrome, especially those with extreme patellar tilt and
      lateral shift malalignments.

PMID- 18337359
TI  - Prevention of overuse injuries by a concurrent exercise program in subjects
      exposed to an increase in training load: a randomized controlled trial of 1020
      army recruits.
AB  - BACKGROUND: It is unknown whether an exercise program can prevent overuse
      injuries in the lower extremity. An often encountered and important risk factor
      for the development of lower extremity overuse injuries is an abrupt increase in
      activity level. HYPOTHESIS: A preventive training program based on a literature
      review of intrinsic risk factors, and performed concurrent with an increase in
      physical activity, can reduce the incidence of overuse knee injuries and medial
      tibial stress syndrome, as well as increase running distance. STUDY DESIGN:
      Randomized controlled trial; Level of evidence, 1. METHODS: A total of 1020
      soldiers aged 20.9 years (range, 19-26 years) undergoing 3 months of basic
      military training consecutively enrolled from December 2004 to December 2005. The
      prevention program consisted of an exercise program of 15 minutes' duration 3
      times a week, including 5 exercises for strength, flexibility, and coordination;
      the placebo program consisted of 5 exercises for the upper body. RESULTS: During
      the observation period, 223 subjects sustained an injury, with 50 and 48 of these
      fulfilling the study criteria for overuse knee injuries or medial tibial stress
      syndrome, respectively. There were no significant differences in incidence of
      injury between the prevention group and the placebo group (incidence, 0.22 vs
      0.19; P = .162; relative risk = 1.05 [range, 0.98-1.11]). The soldiers in the
      prevention group had the greater improvement in running distance in 12-minute run
      tests (82 vs 43 m; P = .037). CONCLUSION: An exercise program with an emphasis on
      muscular strengthening, coordination, and flexibility based on intrinsic risk
      factors identified through a literature review did not influence the risk of
      developing overuse knee injuries or medial tibial stress syndrome in subjects
      undergoing an increase in physical activity. The program increased maximal
      running distance in a 12-minute test.

PMID- 18337360
TI  - Baseline cortical excitability determines whether TMS disrupts or facilitates
      behavior.
AB  - Transcranial magnetic stimulation (TMS) is increasingly used to modify brain
      activity noninvasively and to study brain-behavior relations. However, results
      can be variable and the conditions that affect the functional efficacy of TMS
      remain unclear. Here we show that on-line TMS can either facilitate or suppress
      perceptual functions depending on the baseline level of activity of the targeted
      brain region. When TMS was applied over the motion selective region V5/MT during
      a simple motion-detection task, subjects' motion-detection ability was impaired.
      Similarly, suppression of V5/MT activity using off-line 1 Hz repetitive TMS
      (rTMS) disrupted performance in a subsequent motion-detection task. However,
      paradoxically, on-line V5/MT TMS had a facilitatory effect on motion detection if
      V5/MT had been suppressed by off-line 1-Hz rTMS prior to the motion-detection
      task. These results demonstrate that TMS can have an unexpected facilitatory
      effect on behavior when the targeted neural population is in a suppressed state.
      Our findings provide further evidence for the view that the effects of TMS are
      modulated by the initial activation state of the targeted neural population.

PMID- 18337361
TI  - The brain stem saccadic burst generator encodes gaze in three-dimensional space.
AB  - When we look between objects located at different depths the horizontal movement
      of each eye is different from that of the other, yet temporally synchronized.
      Traditionally, a vergence-specific neuronal subsystem, independent from other
      oculomotor subsystems, has been thought to generate all eye movements in depth.
      However, recent studies have challenged this view by unmasking interactions
      between vergence and saccadic eye movements during disconjugate saccades. Here,
      we combined experimental and modeling approaches to address whether the premotor
      command to generate disconjugate saccades originates exclusively in "vergence
      centers." We found that the brain stem burst generator, which is commonly assumed
      to drive only the conjugate component of eye movements, carries substantial
      vergence-related information during disconjugate saccades. Notably, facilitated
      vergence velocities during disconjugate saccades were synchronized with the burst
      onset of excitatory and inhibitory brain stem saccadic burst neurons (SBNs).
      Furthermore, the time-varying discharge properties of the majority of SBNs (>70%)
      preferentially encoded the dynamics of an individual eye during disconjugate
      saccades. When these experimental results were implemented into a computer-based
      simulation, to further evaluate the contribution of the saccadic burst generator
      in generating disconjugate saccades, we found that it carries all the vergence
      drive that is necessary to shape the activity of the abducens motoneurons to
      which it projects. Taken together, our results provide evidence that the premotor
      commands from the brain stem saccadic circuitry, to the target motoneurons, are
      sufficient to ensure the accurate control shifts of gaze in three dimensions.

PMID- 18337362
TI  - Biophysical properties of human Na v1.7 splice variants and their regulation by
      protein kinase A.
AB  - The sodium channel Na(v)1.7 is preferentially expressed in nociceptive neurons
      and is believed to play a crucial role in pain sensation. Four alternative splice
      variants are expressed in human dorsal root ganglion neurons, two of which differ
      in exon 5 by two amino acids in the S3 segment of domain I (exons 5A and 5N). Two
      others differ in exon 11 by the presence (11L) or absence (11S) of an 11 amino
      acid sequence in the loop between domains I and II, an important region for PKA
      regulation. In the present study, we used the whole cell configuration of the
      patch-clamp technique to investigate the biophysical properties and 8-bromo
      cyclic adenosine monophosphate (8Br-cAMP) modulation of these splice variants
      expressed in tsA201 cells in the presence of the beta(1)-subunit. The alternative
      splicing of Na(v)1.7 had no effect on most of the biophysical properties of this
      channel, including activation, inactivation, and recovery from inactivation.
      However, development of inactivation experiments revealed that the isoform
      containing exon 5A had slower kinetics of inactivation for negative potentials
      than that of the variant containing exon 5N. This difference was associated with
      higher ramp current amplitudes for isoforms containing exon 5A. Moreover, 8Br
      cAMP-mediated phosphorylation induced a negative shift of the activation curve of
      variants containing exon 11S, whereas inactivation properties were unchanged.
      Isoforms with exon 11L were not modulated by 8Br-cAMP-induced phosphorylation. We
      conclude that alternative splicing of human Na(v)1.7 can specifically modulate
      the biophysical properties and cAMP-mediated regulation of this channel. Changing
      the proportions of these variants may thus influence neuronal excitability and
      pain sensation.

PMID- 18337363
TI  - Intercostal and abdominal respiratory motoneurons in the neonatal rat spinal
      cord: spatiotemporal organization and responses to limb afferent stimulation.
AB  - Respiration requires the coordinated rhythmic contractions of diverse muscles to
      produce ventilatory movements adapted to organismal requirements. During fast
      locomotion, locomotory and respiratory movements are coordinated to reduce
      mechanical conflict between these functions. Using semi-isolated and isolated in
      vitro brain stem-spinal cord preparations from neonatal rats, we have
      characterized for the first time the respiratory patterns of all spinal
      intercostal and abdominal motoneurons and explored their functional relationship
      with limb sensory inputs. Neuroanatomical and electrophysiological procedures
      were initially used to locate intercostal and abdominal motoneurons in the cord.
      Intercostal motoneuron somata are distributed rostrocaudally from C(7)-T(13)
      segments. Abdominal motoneuron somata lie between T(8) and L(2). In accordance
      with their soma distributions, inspiratory intercostal motoneurons are recruited
      in a rostrocaudal sequence during each respiratory cycle. Abdominal motoneurons
      express expiratory-related discharge that alternates with inspiration. Lesioning
      experiments confirmed the pontine origin of this expiratory activity, which was
      abolished by a brain stem transection at the rostral boundary of the VII nucleus,
      a critical area for respiratory rhythmogenesis. Entrainment of fictive
      respiratory rhythmicity in intercostal and abdominal motoneurons was elicited by
      periodic low-threshold dorsal root stimulation at lumbar (L(2)) or cervical
      (C(7)) levels. These effects are mediated by direct ascending fibers to the
      respiratory centers and a combination of long-projection and polysynaptic
      descending pathways. Therefore the isolated brain stem-spinal cord in vitro
      generates a complex pattern of respiratory activity in which alternating
      inspiratory and expiratory discharge occurs in functionally identified spinal
      motoneuron pools that are in turn targeted by both forelimb and hindlimb somatic
      afferents to promote locomotor-respiratory coupling.

PMID- 18337364
TI  - Hand position affects saccadic reaction times in monkeys and humans.
AB  - In daily life, activities requiring the hand and eye to work separately are as
      frequent as activities requiring tight eye-hand coordination, and we effortlessly
      switch from one type of activity to the other. Such flexibility is unlikely to be
      achieved without each effector "knowing" where the other one is at all times,
      even when it is static. Here, we provide behavioral evidence that the mere
      position of the static hand affects one eye movement parameter: saccadic reaction
      time. Two monkeys were trained and 11 humans instructed to perform nondelayed or
      delayed visually guided saccades to either a right or a left target while holding
      their hand at a location either near or far from the eye target. From trial to
      trial, target locations and hand positions varied pseudorandomly. Subjects were
      tested both when they could and when they could not see their hand. The main
      findings are 1) the presence of the static hand in the workspace did affect
      saccade initiation; 2) this interaction persisted when the hand was invisible; 3)
      it was strongly influenced by the delay duration: hand-target proximity retarded
      immediate saccades, whereas it could hasten delayed saccades; and 4) this held
      true both for humans and for each of the two monkeys. We propose that both visual
      and nonvisual hand position signals are used by the primates' oculomotor system
      for the planning and execution of saccades, and that this may result in a hand
      eye competition for spatial attentional resources that explains the delay
      dependent reversal observed.

PMID- 18337365
TI  - Human updating of visual motion direction during head rotations.
AB  - Previous studies have demonstrated that human subjects update the location of
      visual targets for saccades after head and body movements and in the absence of
      visual feedback. This phenomenon is known as spatial updating. Here we
      investigated whether a similar mechanism exists for the perception of motion
      direction. We recorded eye positions in three dimensions and behavioral responses
      in seven subjects during a motion task in two different conditions: when the
      subject's head remained stationary and when subjects rotated their heads around
      an anteroposterior axis (head tilt). We demonstrated that after head-tilt
      subjects updated the direction of saccades made in the perceived stimulus
      direction (direction of motion updating), the amount of updating varied across
      subjects and stimulus directions, the amount of motion direction updating was
      highly correlated with the amount of spatial updating during a memory-guided
      saccade task, subjects updated the stimulus direction during a two-alternative
      forced-choice direction discrimination task in the absence of saccadic eye
      movements (perceptual updating), perceptual updating was more accurate than
      motion direction updating involving saccades, and subjects updated motion
      direction similarly during active and passive head rotation. These results
      demonstrate the existence of an updating mechanism for the perception of motion
      direction in the human brain that operates during active and passive head
      rotations and that resembles the one of spatial updating. Such a mechanism
      operates during different tasks involving different motor and perceptual skills
      (saccade and motion direction discrimination) with different degrees of accuracy.

PMID- 18337366
TI  - How do brain areas communicate during the processing of noxious stimuli? An
      analysis of laser-evoked event-related potentials using the Granger causality
      index.
AB  - Several imaging techniques have identified different brain areas involved in the
      processing of noxious stimulation and thus in the constitution of pain. However,
      only little is known how these brain areas communicate with one another after
      activation by stimulus processing and which areas directionally affect or
      modulate the activity of succeeding areas. One measure for the analysis of such
      interactions is represented by the Granger Causality Index (GCI). In applying
      time-varying bivariate and partial variants of this concept (tvGCI), the aim of
      the present study was to investigate the interaction of neural activities between
      a set of scalp electrodes that best represent the brain electrical neural
      activity of major cortical areas involved in the processing of noxious laser-heat
      stimuli and their variation in time. Bivariate and partial tvGCIs were calculated
      within four different intervals of laser-evoked event-related potentials (LEPs)
      including a baseline period prior to stimulus application and three intervals
      immediately following stimulus application, i.e., between 170 and 200 ms (at the
      N2 component), between 260 and 320 ms (P2 component), and between 320 and 400 ms
      (P3 component of LEPs). Results show some similarities, but also some striking
      differences between bivariate and partial tvGCIs. These differences might be
      explained by the nature of bivariate and partial tvGCIs. However, both tvGCI
      approaches revealed a directed interaction between medial and lateral electrodes
      of the centroparietal region. This result was interpreted as a directed
      interaction between the anterior cingulate cortex and the secondary somatosensory
      cortex and the insula, structures that are significantly involved in the
      constitution of pain.

PMID- 18337367
TI  - Neurotensin enhances GABAergic activity in rat hippocampus CA1 region by
      modulating L-type calcium channels.
AB  - Neurotensin (NT) is a tridecapeptide that interacts with three NT receptors;
      NTS1, NTS2, and NTS3. Although NT has been reported to modulate GABAergic
      activity in the brain, the underlying cellular and molecular mechanisms of NT are
      elusive. Here, we examined the effects of NT on GABAergic transmission and the
      involved cellular and signaling mechanisms of NT in the hippocampus. Application
      of NT dose-dependently increased the frequency of spontaneous inhibitory
      postsynaptic currents (sIPSCs) recorded from CA1 pyramidal neurons with no
      effects on the amplitude of sIPSCs. NT did not change either the frequency or the
      amplitude of miniature (m)IPSCs recorded in the presence of tetrodotoxin. Triple
      immunofluorescent staining of recorded interneurons demonstrated the expression
      of NTS1 on GABAergic interneurons. NT increased the action potential firing rate
      but decreased the afterhyperpolarization (AHP) amplitude in identified CA1
      interneurons. Application of L-type calcium channel blockers (nimodipine and
      nifedipine) abolished NT-induced increases in action potential firing rate and
      sIPSC frequency and reduction in AHP amplitude, suggesting that the effects of NT
      are mediated by interaction with L-type Ca(2+) channels. NT-induced increase in
      sIPSC frequency was blocked by application of the specific NTS1 antagonist
      SR48692, the phospholipase C (PLC) inhibitor U73122, the IP(3) receptor
      antagonist 2-APB, and the protein kinase C inhibitor GF109203X, suggesting that
      NT increases gamma-aminobutyric acid release via a PLC pathway. Our results
      provide a cellular mechanism by which NT controls GABAergic neuronal activity in
      hippocampus.

PMID- 18337368
TI  - Modulation of trigeminal spinal subnucleus caudalis neuronal activity following
      regeneration of transected inferior alveolar nerve in rats.
AB  - Modulation of trigeminal spinal subnucleus caudalis neuronal activity following
      regeneration of transected inferior alveolar nerve in rats. To clarify the
      neuronal mechanisms of abnormal pain in the face innervated by the regenerated
      inferior alveolar nerve (IAN), nocifensive behavior, trigeminal ganglion neuronal
      labeling following Fluorogold (FG) injection into the mental skin, and trigeminal
      spinal subnucleus caudalis (Vc) neuronal properties were examined in rats with
      IAN transection. The mechanical escape threshold was significantly higher at 3
      days and lower at 14 days after IAN transection, whereas head withdrawal latency
      to heat was significantly longer at 3, 14, and 60 days after IAN transection. The
      number of FG-labeled ganglion neurons was significantly reduced at 3 days after
      IAN transection but increased at 14 and 60 days. The number of wide dynamic range
      (WDR) neurons with background (BG) activity was significantly higher at 14 and 60
      days after IAN transection compared with naive rats, and the number of WDR and
      low-threshold mechanoreceptive (LTM) neurons with irregularly bursting BG
      activity was increased at these two time points. Mechanically evoked responses
      were significantly larger in WDR and LTM neurons 14 days after IAN transection
      compared with naive rats. Heat- and cold-evoked responses in WDR neurons were
      significantly lower at 14 days after transection compared with naive rats.
      Mechanoreceptive fields were also significantly larger in WDR and LTM neurons at
      14 and 60 days after IAN transection. These findings suggest that these
      alterations may be involved in the development of mechanical allodynia in the
      cutaneous region innervated by the regenerated IAN.

PMID- 18337369
TI  - Body-tilt and visual verticality perception during multiple cycles of roll
      rotation.
AB  - To assess the effects of degrading canal cues for dynamic spatial orientation in
      human observers, we tested how judgments about visual-line orientation in space
      (subjective visual vertical task, SVV) and estimates of instantaneous body tilt
      (subjective body-tilt task, SBT) develop in the course of three cycles of
      constant-velocity roll rotation. These abilities were tested across the entire
      tilt range in separate experiments. For comparison, we also obtained SVV data
      during static roll tilt. We found that as tilt increased, dynamic SVV responses
      became strongly biased toward the head pole of the body axis (A-effect), as if
      body tilt was underestimated. However, on entering the range of near-inverse
      tilts, SVV responses adopted a bimodal pattern, alternating between A-effects
      (biased toward head-pole) and E-effects (biased toward feet-pole). Apart from an
      onset effect, this tilt-dependent pattern of systematic SVV errors repeated
      itself in subsequent rotation cycles with little sign of worsening performance.
      Static SVV responses were qualitatively similar and consistent with previous
      reports but showed smaller A-effects. By contrast, dynamic SBT errors were small
      and unimodal, indicating that errors in visual-verticality estimates were not
      caused by errors in body-tilt estimation. We discuss these results in terms of
      predictions from a canal-otolith interaction model extended with a leaky
      integrator and an egocentric bias mechanism. We conclude that the egocentric-bias
      mechanism becomes more manifest during constant velocity roll-rotation and that
      perceptual errors due to incorrect disambiguation of the otolith signal are small
      despite the decay of canal signals.

PMID- 18337370
TI  - Spatiotemporally graded NMDA spike/plateau potentials in basal dendrites of
      neocortical pyramidal neurons.
AB  - Glutamatergic inputs clustered over approximately 20-40 microm can elicit local N
      methyl-D-aspartate (NMDA) spike/plateau potentials in terminal dendrites of
      cortical pyramidal neurons, inspiring the notion that a single terminal dendrite
      can function as a decision-making computational subunit. A typical terminal basal
      dendrite is approximately 100-200 microm long: could it function as multiple
      decision-making subunits? We test this by sequential focal stimulation of
      multiple sites along terminal basal dendrites of layer 5 pyramidal neurons in rat
      somatosensory cortical brain slices, using iontophoresis or uncaging of brief
      glutamate pulses. There was an approximately sevenfold spatial gradient in
      average spike/plateau amplitude measured at the soma, from approximately 3 mV for
      distal inputs to approximately 23 mV for proximal inputs. Spike/plateaus were
      NMDA receptor (NMDAR) conductance-dominated at all locations. Large Ca(2+)
      transients accompanied spike/plateaus over a approximately 10- to 40-microm zone
      around the input site; smaller Ca(2+) transients extended approximately uniformly
      to the dendritic tip. Spike/plateau duration grew with increasing glutamate and
      depolarization; high Ca(2+) zone size grew with spike/plateau duration. The
      minimum high Ca(2+) zone half-width (just above NMDA spike threshold) increased
      from distal (approximately 10 microm) to proximal locations (approximately 25
      microm), as did the NMDA spike glutamate threshold. Depolarization reduced
      glutamate thresholds. Simulations exploring multi-site interactions based on this
      demonstrate that if appropriately timed and localized inputs occur in vivo, a
      single basal dendrite could correspond to a cascade of multiple co-operating
      dynamic decision-making subunits able to retain information for hundreds of
      milliseconds, with increasing influence on neural output from distal to proximal.
      Dendritic NMDA spike/plateaus are thus well-suited to support graded persistent
      firing.

PMID- 18337371
TI  - Forskolin induces NMDA receptor-dependent potentiation at a central synapse in
      the leech.
AB  - In vertebrate hippocampal neurons, application of forskolin (an adenylyl cyclase
      activator) and rolipram (a phosphodiesterase inhibitor) is an effective technique
      for inducing chemical long-term potentiation (cLTP) that is N-methyl-d-aspartate
      (NMDA) receptor (NMDAR)-dependent. However, it is not known whether forskolin
      induces a similar potentiation in invertebrate synapses. Therefore, we examined
      whether forskolin plus rolipram treatment could induce potentiation at a known
      glutamatergic synapse in the leech (Hirudo sp.), specifically between the
      pressure (P) mechanosensory and anterior pagoda (AP) neurons. Perfusion of
      isolated ganglia with forskolin (50 muM) in conjunction with rolipram (0.1 muM)
      in Mg(2+)-free saline significantly potentiated the P-to-AP excitatory
      postsynaptic potential. Application of 2-amino-5-phosphonovaleric acid (APV, 100
      muM), a competitive NMDAR antagonist, blocked the potentiation, indicating P-to
      AP potentiation is NMDAR-dependent. Potentiation was blocked by injection of bis
      (o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA, 1 mM) into the postsynaptic
      cell, but not by BAPTA injection into the presynaptic neuron, indicating a
      requirement for postsynaptic elevation of intracellular Ca(2+). Application of db
      cAMP mimicked the potentiating effects of forskolin, and Rp-cAMP, an inhibitor of
      protein kinase A, blocked forskolin-induced potentiation. Potentiation was also
      blocked by autocamtide-2-related inhibitory peptide (AIP), indicating a
      requirement for activation of Ca(2+)/calmodulin-dependent kinase II (CaMKII).
      Finally, potentiation was blocked by botulinum toxin, suggesting that trafficking
      of glutamate receptors also plays a role in this form of synaptic plasticity.
      These experiments demonstrate that techniques used to induce cLTP in vertebrate
      synapses also induce NMDAR-dependent potentiation in the leech CNS and that many
      of the cellular processes that mediate LTP are conserved between vertebrate and
      invertebrate phyla.

PMID- 18337372
TI  - Artificial dirt: microfluidic substrates for nematode neurobiology and behavior.
AB  - With a nervous system of only 302 neurons, the free-living nematode
      Caenorhabditis elegans is a powerful experimental organism for neurobiology.
      However, the laboratory substrate commonly used in C. elegans research, a planar
      agarose surface, fails to reflect the complexity of this organism's natural
      environment, complicates stimulus delivery, and is incompatible with high
      resolution optophysiology experiments. Here we present a new class of
      microfluidic devices for C. elegans neurobiology and behavior: agarose-free,
      micron-scale chambers and channels that allow the animals to crawl as they would
      on agarose. One such device mimics a moist soil matrix and facilitates rapid
      delivery of fluid-borne stimuli. A second device consists of sinusoidal channels
      that can be used to regulate the waveform and trajectory of crawling worms. Both
      devices are thin and transparent, rendering them compatible with high-resolution
      microscope objectives for neuronal imaging and optical recording. Together, the
      new devices are likely to accelerate studies of the neuronal basis of behavior in
      C. elegans.

PMID- 18337373
TI  - Activity of ventroposterior thalamus neurons during rotation and translation in
      the horizontal plane in the alert squirrel monkey.
AB  - The firing behavior of 107 vestibular-sensitive neurons in the ventroposterior
      thalamus was studied in two alert squirrel monkeys during whole body rotation and
      translation in the horizontal plane. Vestibular-sensitive neurons were
      distributed primarily along the anterior and posterior borders of ventroposterior
      nuclei; three clusters of these neurons could be distinguished based on their
      location and inputs. Eighty-four neurons responded to rotation; 66 (78%) of them
      responded to rotation only and 18 (22%) to both rotation and translation. Forty
      one neurons were sensitive to linear translation; 23 (56%) of them responded to
      translation only. The population rotational response to 0.5-Hz sinusoids with a
      peak velocity of 40 degrees /s showed a gain of 0.23 +/- 0.15 spike.s(-1).deg(
      1).s(-1) and phase lagging behind the angular velocity by -9.3 +/- 34.1 degrees .
      Although rotational response amplitude increased with the stimulus velocity
      across the range 4-100 degrees /s, the rotational sensitivity decreased with and
      was inversely proportional to the stimulus velocity. The rotational response
      amplitude and sensitivity increased with the stimulus frequency across the range
      0.2-4.0 Hz. The population response to sinusoidal translation at 0.5 Hz and 0.1 g
      amplitude had a gain of 111.3 +/- 53.7 spikes.s(-1).g(-1) and lagged behind
      stimulus acceleration by -71.9 +/- 42.6 degrees . Translational sensitivity
      decreased as acceleration increased and this was inversely proportional to the
      square root of the acceleration. Results of this study imply that changes in the
      discharge rate of vestibular-sensitive thalamic neurons can be approximated using
      power functions of the angular and linear velocity of spatial motion.

PMID- 18337374
TI  - Proteomics analysis identifies molecular targets related to diabetes mellitus
      associated bladder dysfunction.
AB  - Protein expression profiles in rat bladder smooth muscle were compared between
      animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and age
      matched controls at 1 week and 2 months after induction of hyperglycemia with STZ
      treatment. At each time point, protein samples from four STZ-DM and four age
      matched control rat bladder tissues were prepared independently and analyzed
      together across multiple DIGE gels using a pooled internal standard sample to
      quantify expression changes with statistical confidence. A total of 100 spots
      were determined to be significantly changing among the four experimental groups.
      A subsequent mass spectrometry analysis of the 100 spots identified a total of 56
      unique proteins. Of the proteins identified by two-dimensional DIGE/MS, 10
      exhibited significant changes 1 week after STZ-induced hyperglycemia, whereas the
      rest showed differential expression after 2 months. A network analysis of these
      proteins using MetaCore suggested induction of transcriptional factors that are
      too low to be detected by two-dimensional DIGE and identified an enriched cluster
      of down-regulated proteins that are involved in cell adhesion, cell shape
      control, and motility, including vinculin, intermediate filaments, Ppp2r1a, and
      extracellular matrix proteins. The proteins that were up-regulated include
      proteins involved in muscle contraction (e.g. Mrlcb and Ly-GDI), in glycolysis
      (e.g. alpha-enolase and Taldo1), in mRNA processing (e.g. heterogeneous nuclear
      ribonucleoprotein A2/B1), in inflammatory response (e.g. S100A9, Annexin 1, and
      apoA-I), and in chromosome segregation and migration (e.g. Tuba1 and Vil2). Our
      results suggest that the development of diabetes-related complications in this
      model involves the down-regulation of structural and extracellular matrix
      proteins in smooth muscle that are essential for normal muscle contraction and
      relaxation but also induces proteins that are associated with cell proliferation
      and inflammation that may account for some of the functional deficits known to
      occur in diabetic complications of bladder.

PMID- 18337375
TI  - Enhanced protection against bovine tuberculosis after coadministration of
      Mycobacterium bovis BCG with a Mycobacterial protein vaccine-adjuvant combination
      but not after coadministration of adjuvant alone.
AB  - Current efforts are aimed at optimizing the protective efficacy of Mycobacterium
      bovis BCG by the use of vaccine combinations. We have recently demonstrated that
      the protection afforded by BCG alone is enhanced by vaccinating cattle with a
      combination of vaccines comprising BCG and a protein tuberculosis vaccine,
      namely, culture filtrate proteins (CFPs) from M. bovis plus an adjuvant. In the
      current study, three different adjuvant systems were compared. The CFP was
      formulated with a depot adjuvant, dimethyldioctadecyl ammonium bromide (DDA),
      together with one of three different immunostimulants: monophosphoryl lipid A
      (MPL), a synthetic mycobacterial phosphatidylinositol mannoside-2 (PIM2), and a
      synthetic lipopeptide (Pam3Cys-SKKKK [Pam(3)CSK(4)]). Groups of cattle (n =
      10/group) were vaccinated with BCG-CFP-DDA-PIM2, BCG-CFP-DDA-MPL, or BCG-CFP-DDA
      Pam(3)CSK(4). Two additional groups (n = 10) were vaccinated with BCG alone or
      BCG-adjuvant (DDA-MPL), and a control group was left unvaccinated. Protection was
      assessed by challenging the cattle intratracheally with M. bovis. Groups of
      cattle vaccinated with BCG-CFP-DDA-PIM2, BCG-CFP-DDA-MPL, BCG-CFP-DDA
      Pam(3)CSK(4), and BCG alone showed significant reductions in three, three, five,
      and three pathological and microbiological disease parameters, respectively,
      compared to the results for the nonvaccinated group. Vaccination with the
      combination of BCG and the DDA-MPL adjuvant alone abrogated the protection
      conferred by BCG alone. The profiling of cytokine gene expression following
      vaccination, prior to challenge, did not illuminate significant differences which
      could explain the latter result. Vaccination of cattle with a combination of BCG
      and protein tuberculosis vaccine enhances protection against tuberculosis.

PMID- 18337376
TI  - Recombinant attenuated Salmonella enterica serovar typhimurium expressing the
      carboxy-terminal domain of alpha toxin from Clostridium perfringens induces
      protective responses against necrotic enteritis in chickens.
AB  - Clostridium perfringens-induced necrotic enteritis (NE) is a widespread disease
      in chickens that causes high mortality and reduced growth performance.
      Traditionally, NE was controlled by the routine application of antimicrobials in
      the feed, a practice that currently is unpopular. Consequently, there has been an
      increase in the occurrence of NE, and it has become a threat to the current
      objective of antimicrobial-free farming. The pathogenesis of NE is associated
      with the proliferation of C. perfringens in the small intestine and the secretion
      of large amounts of alpha toxin, the major virulence factor. Since there is no
      vaccine for NE, we have developed a candidate live oral recombinant attenuated
      Salmonella enterica serovar Typhimurium vaccine (RASV) that delivers a nontoxic
      fragment of alpha toxin. The 3' end of the plc gene, encoding the C-terminal
      domain of alpha toxin (PlcC), was cloned into plasmids that enable the expression
      and secretion of PlcC fused to a signal peptide. Plasmids were inserted into
      Salmonella enterica serovar Typhimurium host strain chi8914, which has
      attenuating pabA and pabB deletion mutations. Three-day-old broiler chicks were
      orally immunized with 10(9) CFU of the vaccine strain and developed alpha toxin
      neutralizing serum antibodies. When serum from these chickens was added into C.
      perfringens broth cultures, bacterial growth was suppressed. In addition,
      immunofluorescent microscopy showed that serum antibodies bind to the bacterial
      surface. The immunoglobulin G (IgG) and IgA titers in RASV-immunized chickens
      were low; however, when the chickens were given a parenteral boost injection with
      a purified recombinant PlcC protein (rPlcC), the RASV-immunized chickens mounted
      rapid high serum IgG and bile IgA titers exceeding those primed by rPlcC
      injection. RASV-immunized chickens had reduced intestinal mucosal pathology after
      challenge with virulent C. perfringens. These results indicate that oral RASV
      expressing an alpha toxin C-terminal peptide induces protective immunity against
      NE.

PMID- 18337377
TI  - Single-dose, therapeutic vaccination of mice with vesicular stomatitis virus
      expressing human papillomavirus type 16 E7 protein.
AB  - We are developing recombinant attenuated vesicular stomatitis virus (VSV) as a
      vaccine vector to generate humoral and cell-mediated immune responses. Here, we
      explore the use of VSV vaccines for cancer immunotherapy. Immunotherapy targeting
      high-risk human papillomavirus (HPV) lesions has the potential to benefit HPV
      infected individuals and cervical cancer patients by generating cytotoxic T cells
      that kill tumor cells that express viral antigens. A single dose of VSV
      expressing the HPV type 16 (HPV16) E7 oncogene was used for therapeutic
      vaccination of mice bearing TC-1 syngeneic tumors, which express HPV16 E7. HPV16
      E7-specific T cells were generated and displayed cytotoxic activity against the
      tumor cells. By 14 days postvaccination, average tumor volumes were 10-fold less
      in the vaccinated group than in mice that received the empty-vector VSV, and
      regression of preexisting tumors occurred in some cases. This antitumor effect
      was CD8 T-cell dependent. Our results demonstrate antitumor responses to HPV16 E7
      and suggest that recombinant-VSV-based vaccination should be explored as a
      therapeutic strategy for cervical carcinoma and other HPV-associated cancers.

PMID- 18337378
TI  - Prevention of assay interference in infectious-disease serology tests done on the
      liaison platform.
AB  - Immunoassay interference causing unexpected reactive results in magnetic
      microparticle-based assays was detected. A systematic evaluation of Liaison
      Epstein-Barr virus immunoglobulin M showed that 5% of the positive results (0.4%
      of tested samples) could be explained by such interference. Adding chemical
      blocking reagents (polyvinylpyrrolidone and polyvinyl alcohol) to the assay
      buffers partially prevented this phenomenon.

PMID- 18337379
TI  - Mice with pulmonary tuberculosis treated with Mycobacterium vaccae develop
      strikingly enhanced recall gamma interferon responses to M. vaccae cell wall
      skeleton.
AB  - Whole heat-killed Mycobacterium vaccae is used as an immunotherapeutic agent in
      tuberculosis (TB), but the compound(s) that triggers its immunostimulatory
      ability is not known. Here, we show that among different subcellular fractions,
      the cell wall skeleton induced a prominent expression of gamma interferon in
      splenocytes from both non-TB and TB M. vaccae-treated mice.

PMID- 18337380
TI  - Live Mycobacterium avium subsp. paratuberculosis and a killed-bacterium vaccine
      induce distinct subcutaneous granulomas, with unique cellular and cytokine
      profiles.
AB  - Type II (lepromatous) granulomas are characterized by a lack of organization,
      with large numbers of macrophages heavily burdened with bacilli and disorganized
      lymphocyte infiltrations. Type II granulomas are a characteristic feature of the
      enteric lesions that develop during clinical Mycobacterium avium subsp.
      paratuberculosis infection in the bovine. Considering the poor organization and
      function of these granulomas, it is our hypothesis that dendritic cell (DC)
      function within the granuloma is impaired during initial infection. In order to
      test our hypothesis, we used a subcutaneous M. avium subsp. paratuberculosis
      infection model to examine early DC function within M. avium subsp.
      paratuberculosis-induced granulomas. In this model, we first characterized the
      morphology, cellular composition, and cytokine profiles of subcutaneous
      granulomas that develop 7 days after subcutaneous inoculation with either vaccine
      or live M. avium subsp. paratuberculosis. Second, we isolated CD11c(+) cells from
      within granulomas and measured their maturation status and ability to induce T
      cell responses. Our results demonstrate that M. avium subsp. paratuberculosis or
      vaccine administration resulted in the formation of distinct granulomas with
      unique cellular and cytokine profiles. These distinct profiles corresponded to
      significant differences in the phenotypes and functional responses of DCs from
      within the granulomas. Specifically, the DCs from the M. avium subsp.
      paratuberculosis-induced granulomas had lower levels of expression of
      costimulatory and chemokine receptors, suggesting limited maturation. This DC
      phenotype was associated with weaker induction of T-cell proliferation. Taken
      together, these findings suggest that M. avium subsp. paratuberculosis infection
      in vivo influences DC function, which may shape the developing granuloma and
      initial local protection.

PMID- 18337381
TI  - Enzyme-linked immunosorbent assays using novel Japanese encephalitis virus
      antigen improve the accuracy of clinical diagnosis of flavivirus infections.
AB  - The cross-reactive antibodies induced by flavivirus infections confound
      serodiagnosis and pathogenesis, especially in secondary infections caused by
      antigenically closely related yet distinct flaviviruses. The envelope (E)
      glycoprotein fusion peptide contains immunodominant cross-reactive determinants.
      Using a recombinant Japanese encephalitis virus (JEV) premembrane and E
      expression plasmid producing JEV virus-like particles (VLPs), dramatic reductions
      in cross-reactivity were produced by the G106K-L107D (KD) double-mutant VLP
      against a panel of flavivirus murine monoclonal antibodies. Human serum panels
      from patients with recent flavivirus infections were analyzed to compare the
      accuracy of JEV wild-type (WT) and KD VLPs as serodiagnostic antigens in enzyme
      linked immunosorbent assays. Statistical analysis demonstrated significant
      differences in assay performances for accurate determination of current JEV
      infections between WT and KD antigens by detecting immunoglobulin M antibodies at
      a serum dilution of 1:4,000 (likelihood ratios = 2.74 [WT] and 22 [KD]). The
      application and continued development of cross-reactivity-reduced antigens should
      improve both flavivirus infection serodiagnosis and estimates of disease burden.

PMID- 18337384
TI  - Comparison of Neo-Sensitabs tablet diffusion assay with CLSI broth microdilution
      M38-A and disk diffusion methods for testing susceptibility of filamentous fungi
      with amphotericin B, caspofungin, itraconazole, posaconazole, and voriconazole.
AB  - We compared the Neo-Sensitabs tablet assay to both reference M38-A broth
      microdilution and disk diffusion methods for testing the susceptibility of 183
      filamentous isolates to amphotericin B, caspofungin, itraconazole, posaconazole,
      and voriconazole. Neo-Sensitabs and disk assay inhibition zone diameters, in
      millimeters, were obtained on nonsupplemented Mueller-Hinton agar at 16 to 48 h.
      The reproducibility of zone diameters (i.e., the percentage of replicate zone
      diameters that were within 2 standard deviations of the means), their correlation
      with either MICs or minimum effective concentrations (for caspofungin only), and
      the categorical agreement were similar between tablet and disk assays (93 to 100%
      [R, >0.70] and 79 to 96%, respectively) with four of the five agents. The
      exceptions were the results for posaconazole tablets (R, 0.686; disk, 0.757; 84%
      categorical agreement for tablet and 96% for disk). These data suggest the
      potential value of the Neo-Sensitabs assay for testing 5-microg caspofungin and 1
      microg voriconazole posaconazole tablets against all mold isolates, 8-microg
      itraconazole and 5-microg tablets against all mold isolates except zygomycetes,
      and 10-microg amphotericin B tablets against zygomycete isolates only.

PMID- 18337382
TI  - Specificity of subcapsular antibody responses in Ethiopian patients following
      disease caused by serogroup A meningococci.
AB  - Dissecting the specificities of human antibody responses following disease caused
      by serogroup A meningococci may be important for the development of improved
      vaccines. We performed a study of Ethiopian patients during outbreaks in 2002 and
      2003. Sera were obtained from 71 patients with meningitis caused by bacteria of
      sequence type 7, as confirmed by PCR or culture, and from 113 Ethiopian controls.
      Antibody specificities were analyzed by immunoblotting (IB) against outer
      membrane antigen extracts of a reference strain and of the patients' own isolates
      and by enzyme-linked immunosorbent assay for immunoglobulin G (IgG) levels
      against lipooligosaccharide (LOS) L11 and the proteins NadA and NspA. IB revealed
      that the main antigens targeted were the proteins PorA, PorB, RmpM, and Opa/OpcA,
      as well as LOS. MenA disease induced significant increases in IgG against LOS L11
      and NadA. The IgG levels against LOS remained elevated following disease, whereas
      the IgG anti-NadA levels returned to acute-phase levels in the late convalescent
      phase. Among adults, the anti-LOS IgG levels were similar in acute-phase patient
      sera as in control sera, whereas anti-NadA IgG levels were significantly higher
      in acute-phase sera than in controls. The IgG antibody levels against LOS and
      NadA correlated moderately but significantly with serum bactericidal activity
      against MenA strains. Future studies on immune response during MenA disease
      should take into account the high levels of anti-MenA polysaccharide IgG commonly
      found in the population and seek to clarify the role of antibodies against
      subcapsular antigens in protection against MenA disease.

PMID- 18337385
TI  - Thoracic vertebral actinomycosis: Actinomyces israelii and Fusobacterium
      nucleatum.
AB  - Actinomyces spp. are considered rare pathogens in today's medicine, especially
      with thoracic vertebral involvement. Classic actinomycosis (50%) presents as an
      oral-cervicofacial ("lumpy jaw") infection. This report describes a case of
      spinal cord compression caused by Actinomyces israelii with the coisolation of
      Fusobacterium nucleatum. There are limited numbers of similar cases.

PMID- 18337386
TI  - Prospective evaluation of rapid antigen tests for diagnosis of respiratory
      syncytial virus and human metapneumovirus infections.
AB  - Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are two
      important viral pathogens that cause respiratory tract infections in the
      pediatric population. The rapid detection of these agents allows the prompt
      isolation and treatment of infected patients. In the present prospective study,
      we evaluated the performances of four rapid antigen detection assays, including a
      rapid chromatographic immunoassay (CIA) for RSV (Directigen EZ RSV; Becton
      Dickinson, Sparks, MD), a direct fluorescent-antibody assay (DFA) for RSV
      (Bartels; Trinity Biotech, Carlsbad, CA), and two DFAs for hMPV manufactured by
      Diagnostic Hybrids Inc. (DHI; Athens, OH) and Imagen (Oxoid Ltd., Basingstoke,
      Hampshire, United Kingdom). The clinical specimens tested comprised 515
      nasopharyngeal aspirates submitted to the Clinical Microbiology Laboratory at
      Hartford Hospital from 1 November 2006 to 21 April 2007. Compared to the results
      of real-time reverse transcription-PCR (RT-PCR), the CIA had a sensitivity of
      79.8% and a specificity of 89.5%. The RSV DFA with Bartels reagents showed a
      sensitivity of 94.1% and a specificity of 96.8%. For hMPV, the sensitivity and
      specificity were 62.5% and 99.8%, respectively, for the DHI DFA and 63.2% and
      100%, respectively, for the Imagen DFA. The hands-on and test turnaround times
      for CIA were 10 and 30 to 60 min, respectively, and the hands-on and test
      turnaround times for the RSV and hMPV DFAs were 30 and 105 min, respectively. We
      conclude that while the RSV CIA is user-friendly, it lacks sensitivity and
      specificity, especially during off-peak months. In contrast, the RSV DFA is more
      sensitive and specific, but interpretation of its results is subjective and it
      demands technical time and expertise. Similarly, both hMPV DFAs are highly
      specific in comparison to the results of RT-PCR, but their sensitivities await
      further improvements.

PMID- 18337387
TI  - Novel wide-range quantitative nested real-time PCR assay for Mycobacterium
      tuberculosis DNA: clinical application for diagnosis of tuberculous meningitis.
AB  - Although the "gold standard" for diagnosis of tuberculous meningitis (TBM) is
      bacterial isolation of Mycobacterium tuberculosis, there are still several
      complex issues. Recently, we developed an internally controlled novel wide-range
      quantitative nested real-time PCR (WR-QNRT-PCR) assay for M. tuberculosis DNA in
      order to rapidly diagnose TBM. For use as an internal control calibrator to
      measure the copy number of M. tuberculosis DNA, an original new-mutation plasmid
      (NM-plasmid) was developed. Due to the development of the NM-plasmid, the WR-QNRT
      PCR assay demonstrated statistically significant accuracy over a wide detection
      range (1 to 10(5) copies). In clinical applications, the WR-QNRT-PCR assay
      revealed sufficiently high sensitivity (95.8%) and specificity (100%) for 24
      clinically suspected TBM patients. In conditional logistic regression analysis, a
      copy number of M. tuberculosis DNA (per 1 ml of cerebrospinal fluid) of >8,000
      was an independent risk factor for poor prognosis for TBM (i.e., death) (odds
      ratio, 16.142; 95% confidence interval, 1.191 to 218.79; P value, 0.0365). In
      addition, the copy numbers demonstrated by analysis of variance statistically
      significant alterations (P < 0.01) during the clinical treatment course for 10
      suspected TBM patients. In simple regression analysis, the significant
      correlation (R(2) = 0.597; P < 0.0001) was demonstrated between copy number and
      clinical stage of TBM. We consider the WR-QNRT-PCR assay to be a useful and
      advanced assay technique for assessing the clinical treatment course of TBM.

PMID- 18337388
TI  - New and sensitive assay for determining Pseudomonas aeruginosa metallo-beta
      lactamase resistance to imipenem.
AB  - We present an imipenem lysate metallo-beta-lactamase (MBL) functional assay. This
      assay eliminates false-positive results due to the bactericidal effects of EDTA,
      can be performed with inexpensive reagents available in most laboratories, and is
      as accurate as the MBL Etest. It is appropriate for both high-accuracy screens
      and laboratories in developing countries with limited resources.

PMID- 18337389
TI  - RNase P RNA gene (rnpB) phylogeny of Hemoplasmas and other Mycoplasma species.
AB  - Partial sequences of the RNase P RNA gene (rnpB) were obtained from a number of
      hemoplasmas and other Mycoplasma species. Phylogenetic analysis of these
      sequences showed that all hemoplasmas were present within a single clade and were
      most closely related to Mycoplasma fastidiosum, similar to the results found with
      16S rRNA gene phylogeny.

PMID- 18337390
TI  - Novel wide-range quantitative nested real-time PCR assay for Mycobacterium
      tuberculosis DNA: development and methodology.
AB  - Previously, we designed an internally controlled quantitative nested real-time
      (QNRT) PCR assay for Mycobacterium tuberculosis DNA in order to rapidly diagnose
      tuberculous meningitis. This technique combined the high sensitivity of nested
      PCR with the accurate quantification of real-time PCR. In this study, we
      attempted to improve the original QNRT-PCR assay and newly developed the wide
      range QNRT-PCR (WR-QNRT-PCR) assay, which is more accurate and has a wider
      detection range. For use as an internal-control "calibrator" to measure the copy
      number of M. tuberculosis DNA, an original new-mutation plasmid (NM-plasmid) was
      developed. It had artificial random nucleotides in five regions annealing
      specific primers and probes. The NM-plasmid demonstrated statistically uniform
      amplifications (F = 1.086, P = 0.774) against a range (1 to 10(5)) of copy
      numbers of mimic M. tuberculosis DNA and was regarded as appropriate for use as a
      new internal control in the WR-QNRT-PSR assay. In addition, by the optimization
      of assay conditions in WR-QNRT-PCR, two-step amplification of target DNA was
      completely consistent with the standard curve of this assay. Due to the
      development of the NM-plasmid as the new internal control, significantly improved
      quantitative accuracy and a wider detection range were realized with the WR-QNRT
      PCR assay. In the next study, we will try to use this novel assay method with
      actual clinical samples and examine its clinical usefulness.

PMID- 18337391
TI  - Stability of Trichomonas vaginalis DNA in urine specimens.
AB  - Trichomonas vaginalis is an important pathogen in both men and women. Culture is
      considered the diagnostic gold standard, although studies have shown that PCR is
      more sensitive than either culture or wet mount for the diagnosis of T. vaginalis
      infections. We sought to identify a simple method for stabilizing T. vaginalis
      DNA in urine samples that could be easily applied to molecular testing. The
      stability of T. vaginalis DNA in 40 urine samples was assessed by storage for
      various times at either 4 degrees C or room temperature with or without the
      Becton Dickinson urine preservative transport (UPT) kit. Overall, there was
      better stability of T. vaginalis DNA when specimens were stored at 4 degrees C
      than when they were stored at 20 to 22 degrees C and when the UPT system was
      used. T. vaginalis DNA was stable in specimens stored without using the UPT at 4
      degrees C for about 3 days and at room temperature for only 1 day. For specimens
      placed in the UPT within 24 h (times of 1, 6, and 24 h) of collection, the DNA
      was stable for up to 30 days when stored at 4 degrees C. For specimens stored at
      room temperature, the urine should be added to the UPT ideally within 1 hour of
      collection, and in this case the DNA remained stable for up to 30 days. When
      storing specimens at room temperature, a delay of 24 h prior to adding to UPT led
      to an unacceptably high loss of assay sensitivity.

PMID- 18337392
TI  - Evaluation of 16S rRNA gene-based PCR assays for genus-level identification of
      Helicobacter species.
AB  - The inclusivity, exclusivity, and detection limit of six 16S rRNA gene-based
      Helicobacter genus-specific PCR assays were examined. Five out of six assays were
      100% inclusive, but the tests varied considerably in their exclusivity (9.1 to
      95.5%). The clinical detection limit varied between 10(3) and 1 viable bacterial
      cell per reaction mixture.

PMID- 18337393
TI  - Revascularization results in the Interventional Management of Stroke II trial.
AB  - BACKGROUND AND PURPOSE: Our aim was to detail revascularization results,
      including impact on outcome and mortality, in the Interventional Management of
      Stroke (IMS) II trial. MATERIALS AND METHODS: IMS II was designed to obtain
      estimates of the efficacy and safety of reduced-dose intravenous recombinant
      tissue plasminogen activator (rtPA) followed by additional intra-arterial rtPA
      and low-energy sonography via the EKOS Primo Micro-Infusion Catheter at the
      occlusion in selected patients with ischemic stroke treated within 3 hours of
      onset. Revascularization outcomes were detailed and compared with modified Rankin
      Scale scores 0-2, mortality outcomes, and results from IMS I. RESULTS: Complete
      recanalization at 60 minutes occurred in 12 of 29 (41.4%) sonography
      microcatheter-treated occlusions. Complete recanalization was achieved at 2 hours
      or procedure end in 20/29 (68.9%) in the ultrasound catheter-treated group, and
      final thrombolysis in cerebral infarction (TICI) 2/3 reperfusion was achieved in
      18/29 (62.0%) ultrasound-treated subjects. Fifteen-minute angiograms demonstrated
      some recanalization in 69/145 (46.7%) sonography microcatheter treatment
      intervals, compared with 39/111 (35.1%) in IMS I treatments in 23 subjects with
      reliable 15-minute angiograms (P = .046). Pooled IMS I-II data demonstrated that
      partial or complete recanalization occurred in 56/75 (74.6%) and good reperfusion
      (TICI 2/3) occurred in 46/75 (61.3%) of internal carotid artery T and M1
      occlusions. Revascularization correlated with good outcome for TICI 2/3
      reperfusion (P = .0004), TICI 2B/3 reperfusion (P = .0002), and arterial
      occlusive lesion 2/3 recanalization (P = .03). CONCLUSION: IMS II provides
      evidence that the EKOS Primo sonography microcatheter exhibits a trend toward
      improved recanalization of the occlusion compared with a standard microcatheter
      and again confirms the correlation between recanalization and reperfusion with
      good clinical outcome and reduced mortality.

PMID- 18337394
TI  - Neuroendocrine imaging.

PMID- 18337395
TI  - Drd1a-tdTomato BAC transgenic mice for simultaneous visualization of medium spiny
      neurons in the direct and indirect pathways of the basal ganglia.

PMID- 18337396
TI  - Carpet cells regulate glial cell motility in the developing Drosophila eye.

PMID- 18337397
TI  - Knocking down glycosaminoglycan synthesis.

PMID- 18337398
TI  - Capture of auditory motion by vision is represented by an activation shift from
      auditory to visual motion cortex.
AB  - The brain is capable of integrating motion information arising from visual and
      auditory input. Such integration between sensory modalities can aid one another
      and helps to stabilize the motion percept. However, if motion information differs
      between sensory modalities, it can also result in an illusory auditory motion
      percept. This phenomenon is referred to as the cross-modal dynamic capture (CDC)
      illusion. We used functional magnetic resonance imaging to investigate whether
      early visual and auditory motion areas are involved in the generation of this
      illusion. Among the trials containing conflicting audiovisual motion, we compared
      the trials in which CDC occurred to those in which it did not and used a region
      of interest approach to see whether the auditory motion complex (AMC) and the
      visual motion area hMT/V5+ were affected by this illusion. Our results show that
      CDC reduces activation in bilateral auditory motion areas while increasing
      activity in the bilateral hMT/V5+. Interestingly, our data show that the CDC
      illusion is preceded by an enhanced activation that is most dominantly present in
      the ventral intraparietal sulcus. Moreover, we assessed the effect of motion
      coherency, which was found to enhance activation in bilateral hMT/V5+ as well as
      in an area adjacent to the right AMC. Together, our results show that audiovisual
      integration occurs in early motion areas. Furthermore, it seems that the
      cognitive state of subjects before stimulus onset plays an important role in the
      generation of multisensory illusions.

PMID- 18337399
TI  - A new nerve growth factor-mimetic peptide active on neuropathic pain in rats.
AB  - Analysis of the structure of nerve growth factor (NGF)-tyrosine kinase receptor A
      (TrkA) complex, site-directed mutagenesis studies and results from chemical
      modification of amino acid residues have identified loop 1, loop 4, and the N
      terminal region of the NGF molecule as the most relevant for its biological
      activity. We synthesized several peptides mimicking the two loops (1 and 4)
      linked together with an appropriate spacer, with or without the N-terminal
      region. Two peptides named NL1L4 and L1L4 demonstrated good NGF agonist activity
      at a concentration as low as 3 mum. They induced differentiation of chick dorsal
      root ganglia and stimulated tyrosine phosphorylation of TrkA, but not TrkB,
      receptor. In addition L1L4 was able to induce differentiation of PC12 cells. More
      interestingly, the peptide with the highest "in vitro" activity (L1L4) was shown
      to reduce neuropathic behavior and restore neuronal function in a rat model of
      peripheral neuropathic pain, thereby suggesting a potential therapeutic role for
      this NGF-mimetic peptide.

PMID- 18337400
TI  - Age-related regional network of magnetic resonance imaging gray matter in the
      rhesus macaque.
AB  - Human structural neuroimaging studies have supported the preferential effects of
      healthy aging on frontal cortex, but reductions in other brain regions have also
      been observed. We investigated the regional network pattern of gray matter using
      magnetic resonance imaging (MRI) in young adult and old rhesus macaques (RMs) to
      evaluate age effects throughout the brain in a nonhuman primate model of healthy
      aging in which the full complement of Alzheimer's disease (AD) pathology does not
      occur. Volumetric T1 MRI scans were spatially normalized and segmented for gray
      matter using statistical parametric mapping (SPM2) voxel-based morphometry.
      Multivariate network analysis using the scaled subprofile model identified a
      linear combination of two gray matter patterns that distinguished the young from
      old RMs. The combined pattern included reductions in bilateral dorsolateral and
      ventrolateral prefrontal and orbitofrontal and superior temporal sulcal regions
      with areas of relative preservation in vicinities of the cerebellum, globus
      pallidus, visual cortex, and parietal cortex in old compared with young RMs.
      Higher expression of this age-related gray matter pattern was associated with
      poorer performance in working memory. In the RM model of healthy aging, the major
      regionally distributed effects of advanced age on the brain involve reductions in
      prefrontal regions and in the vicinity of the superior temporal sulcus. The age
      related differences in gray matter reflect the effects of healthy aging that
      cannot be attributed to AD pathology, providing support for the targeted effects
      of aging on the integrity of frontal lobe regions and selective temporal lobe
      areas and their associated cognitive functions.

PMID- 18337401
TI  - Appetitive motivation predicts the neural response to facial signals of
      aggression.
AB  - The "behavioral approach system" (BAS) (Gray, 1990) has been primarily associated
      with reward processing and positive affect. However, additional research has
      demonstrated that the BAS plays a role in aggressive behavior, heightened
      experience of anger, and increased attention to facial signals of aggression.
      Using functional magnetic resonance imaging, we show that variation in the BAS
      trait in healthy participants predicts activation in neural regions implicated in
      aggression when participants view facial signals of aggression in others.
      Increased BAS drive (appetitive motivation) was associated with increased
      amygdala activation and decreased ventral anterior cingulate and ventral striatal
      activation to facial signals of aggression, relative to sad and neutral
      expressions. In contrast, increased behavioral inhibition was associated with
      increased activation in the dorsal anterior cingulate, a region involved in the
      perception of fear and threat. Our results provide the first demonstration that
      appetitive motivation constitutes a significant factor governing the function of
      neural regions implicated in aggression, and have implications for understanding
      clinical disorders of aggression.

PMID- 18337402
TI  - Electrophysiological and behavioral evidence demonstrating that predator
      detection alters adaptive behaviors in the snail Lymnaea.
AB  - Stress has been shown to both impair and enhance learning, long-term memory (LTM)
      formation, and/or its recall. The pond snail, Lymnaea stagnalis, both detects and
      responds to the scent of a crayfish predator with multiple stress-related
      behavioral responses. Using both behavioral and electrophysiological evidence,
      this investigation is a first attempt to characterize how an environmentally
      relevant stressor (scent of a predator) enhances LTM formation in Lymnaea. Using
      a training procedure that, in "standard" pond water (PW), results in an
      intermediate-term memory that persists for only 3 h, we found that training
      snails in "crayfish effluent" (CE) induces a memory that persists for 48 h (i.e.,
      its now an LTM). In addition, if we use a training procedure that in PW produces
      an LTM that persists for 1 d, we find that snails trained in CE have an LTM that
      persists for at least 8 d. Furthermore, we describe how a single neuron (RPeD1),
      which has been shown to be a necessary site for LTM formation, reflects the
      behavioral changes in its firing properties that persist for the duration of the
      LTM. Finally, Lymnaea exhibit context-specific memory, that is, when a memory is
      formed in a specific context (food odorant), it is only recalled in that context.
      Here, we found that snails trained in CE demonstrate context generalization, that
      is, memory is recalled in multiple contexts. All data are consistent with the
      hypothesis that learning in a stressful, yet biologically relevant, environment
      enhances LTM and prolongs its retention.

PMID- 18337403
TI  - Progressive ganglion cell degeneration precedes neuronal loss in a mouse model of
      glaucoma.
AB  - Glaucoma is characterized by retinal ganglion cell (RGC) pathology and a
      progressive loss of vision. Previous studies suggest RGC death is responsible for
      vision loss in glaucoma, yet evidence from other neurodegenerative diseases
      suggests axonal degeneration, in the absence of neuronal loss, can significantly
      affect neuronal function. To characterize RGC degeneration in the DBA/2 mouse
      model of glaucoma, we quantified RGCs in mice of various ages using neuronal
      specific nuclear protein (NeuN) immunolabeling, retrograde labeling, and optic
      nerve axon counts. Surprisingly, the number of NeuN-labeled RGCs did not decline
      significantly until 18 months of age, at which time a significant decrease in RGC
      somal size was also observed. Axon dysfunction and degeneration occurred before
      loss of NeuN-positive RGCs, because significant declines in RGC number assayed by
      retrograde tracers and axon counts were observed at 13 months. To examine whether
      axonal dysfunction/degeneration affected gene expression in RGC axons or somas,
      NeuN and neurofilament-heavy (NF-H) immunolabeling was performed along with
      quantitative reverse transcription-PCR for RGC-specific genes in retinas of aged
      DBA/2 mice. Although these mice had similar numbers of NeuN-positive RGCs, the
      expression of neurofilament light, Brn-3b, and Sncg mRNA varied; this variation
      in RGC-specific gene expression was correlated with the appearance of NF-H
      immunoreactive RGC axons. Together, these data support a progression of RGC
      degeneration in this model of glaucoma, beginning with loss of retrograde label,
      where axon dysfunction and degeneration precede neuronal loss. This progression
      of degeneration suggests a need to examine the RGC axon as a locus of pathology
      in glaucoma.

PMID- 18337404
TI  - Human insula activation reflects risk prediction errors as well as risk.
AB  - Understanding how organisms deal with probabilistic stimulus-reward associations
      has been advanced by a convergence between reinforcement learning models and
      primate physiology, which demonstrated that the brain encodes a reward prediction
      error signal. However, organisms must also predict the level of risk associated
      with reward forecasts, monitor the errors in those risk predictions, and update
      these in light of new information. Risk prediction serves a dual purpose: (1) to
      guide choice in risk-sensitive organisms and (2) to modulate learning of
      uncertain rewards. To date, it is not known whether or how the brain accomplishes
      risk prediction. Using functional imaging during a simple gambling task in which
      we constantly changed risk, we show that an early-onset activation in the human
      insula correlates significantly with risk prediction error and that its time
      course is consistent with a role in rapid updating. Additionally, we show that
      activation previously associated with general uncertainty emerges with a delay
      consistent with a role in risk prediction. The activations correlating with risk
      prediction and risk prediction errors are the analogy for risk of activations
      correlating with reward prediction and reward prediction errors for reward
      expectation. As such, our findings indicate that our understanding of the neural
      basis of reward anticipation under uncertainty needs to be expanded to include
      risk prediction.

PMID- 18337405
TI  - Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine
      morphology and activity-dependent synaptic strength.
AB  - In the mature nervous system, changes in synaptic strength correlate with changes
      in neuronal structure. Members of the Nogo-66 receptor family have been
      implicated in regulating neuronal morphology. Nogo-66 receptor 1 (NgR1) supports
      binding of the myelin inhibitors Nogo-A, MAG (myelin-associated glycoprotein),
      and OMgp (oligodendrocyte myelin glycoprotein), and is important for growth cone
      collapse in response to acutely presented inhibitors in vitro. After injury to
      the corticospinal tract, NgR1 limits axon collateral sprouting but is not
      important for blocking long-distance regenerative growth in vivo. Here, we report
      on a novel interaction between NgR1 and select members of the fibroblast growth
      factor (FGF) family. FGF1 and FGF2 bind directly and with high affinity to NgR1
      but not to NgR2 or NgR3. In primary cortical neurons, ectopic NgR1 inhibits FGF2
      elicited axonal branching. Loss of NgR1 results in altered spine morphologies
      along apical dendrites of hippocampal CA1 neurons in vivo. Analysis of
      synaptosomal fractions revealed that NgR1 is enriched synaptically in the
      hippocampus. Physiological studies at Schaffer collateral-CA1 synapses uncovered
      a synaptic function for NgR1. Loss of NgR1 leads to FGF2-dependent enhancement of
      long-term potentiation (LTP) without altering basal synaptic transmission or
      short-term plasticity. NgR1 and FGF receptor 1 (FGFR1) are colocalized to
      synapses, and mechanistic studies revealed that FGFR kinase activity is necessary
      for FGF2-elicited enhancement of hippocampal LTP in NgR1 mutants. In addition,
      loss of NgR1 attenuates long-term depression of synaptic transmission at Schaffer
      collateral-CA1 synapses. Together, our findings establish that physiological NgR1
      signaling regulates activity-dependent synaptic strength and uncover neuronal
      NgR1 as a regulator of synaptic plasticity.

PMID- 18337406
TI  - A role for non-rapid-eye-movement sleep homeostasis in perceptual learning.
AB  - Slow-wave activity (SWA; EEG power density in the 0.75-4.5 Hz range) in non-rapid
      eye-movement (NREM) sleep is the primary marker of sleep homeostasis and thought
      to reflect sleep need. But it is unknown whether the generation of SWA itself
      serves a fundamental function. Previously, SWA has been implicated in brain
      plasticity and learning, yet the evidence for a causal role remains correlative.
      Here, we used acoustic slow-wave suppression to test whether overnight
      improvement in visual texture discrimination, a form of perceptual learning,
      directly depends on SWA during sleep. Two groups of subjects were trained on a
      texture discrimination task (TDT) after baseline sleep, and were tested 24 h
      later, after a 4 h experimental (EX) sleep episode (with or without SWA
      suppression), and again after a night of recovery sleep. In the suppression
      group, SWA during EX sleep was reduced by 30% compared with the control group,
      whereas total sleep time and REM sleep were not affected. Texture discrimination
      improved after EX sleep in the control group but not in the suppression group.
      Moreover, overnight improvement in TDT performance correlated with EEG power
      density during NREM sleep in the frequency range of SWA (maximum r = 0.75 at 0.75
      1.0 Hz) over brain areas involved in TDT learning. We conclude that SWA is an
      important determinant of sleep-dependent gains in perceptual performance, a
      finding that directly implicates processes of sleep homeostasis in learning.

PMID- 18337407
TI  - Nicotine self-administration differentially regulates hypothalamic corticotropin
      releasing factor and arginine vasopressin mRNAs and facilitates stress-induced
      neuronal activation.
AB  - Acute nicotine is a potent stimulus for activation of the stress-responsive
      hypothalamic-pituitary-adrenal (HPA) axis, while chronic nicotine self
      administration (SA) desensitizes the ACTH response to self-administered nicotine
      but cross-sensitizes to mild footshock stress (mFSS). To identify underlying
      mechanisms, we investigated (1) the effects of chronic nicotine SA on the
      coexpression of corticotropin-releasing factor (CRF) and arginine vasopressin
      (AVP) mRNAs, the primary hypothalamic neuropeptides regulating ACTH release, in
      the parvocellular division of paraventricular nucleus (pcPVN), and (2) mFSS
      induced activation of these neurons during nicotine SA. Adult male Sprague Dawley
      rats were given 23 h/d unlimited access to self-administer nicotine (0.03 mg/kg
      per injection, i.v.) for 19 d. Brains were double labeled with fluorescence in
      situ hybridization of CRF and AVP mRNAs and triple labeled after mFSS exposure
      for CRF and AVP mRNAs and c-Fos protein. Chronic nicotine SA significantly
      increased AVP mRNA signal and the number of pcPVN AVP-positive (AVP(+)) neurons
      (twofold to threefold), reduced the number of CRF-positive (CRF(+)) neurons by
      approximately 60%, but increased pcPVN CRF(+)/AVP(+) neuronal number fivefold.
      Significantly, although chronic nicotine SA did not affect total c-Fos expression
      induced by mFSS in pcPVN CRF(+) neurons, the majority of the new CRF(+)/AVP(+)
      population was activated by this heterotypic stressor. These phenotypic neuronal
      alterations may provide the pivotal mechanism underlying the capacity of
      chronically self-administered nicotine to cross-sensitize the HPA response to
      specific stressors, suggesting that nicotine may augment HPA responsiveness to
      specific stressors in human smokers.

PMID- 18337408
TI  - N-terminal mutant huntingtin associates with mitochondria and impairs
      mitochondrial trafficking.
AB  - Huntington's disease (HD) is caused by polyglutamine (polyQ) expansion in
      huntingtin (htt), a large (350 kDa) protein that localizes predominantly to the
      cytoplasm. Proteolytic cleavage of mutant htt yields polyQ-containing N-terminal
      fragments that are prone to misfolding and aggregation. Disease progression in HD
      transgenic models correlates with age-related accumulation of soluble and
      aggregated forms of N-terminal mutant htt fragments, suggesting that multiple
      forms of mutant htt are involved in the selective neurodegeneration in HD.
      Although mitochondrial dysfunction is implicated in the pathogenesis of HD, it
      remains unclear which forms of cytoplasmic mutant htt associate with mitochondria
      to affect their function. Here we demonstrate that specific N-terminal mutant htt
      fragments associate with mitochondria in Hdh(CAG)150 knock-in mouse brain and
      that this association increases with age. The interaction between soluble N
      terminal mutant htt and mitochondria interferes with the in vitro association of
      microtubule-based transport proteins with mitochondria. Mutant htt reduces the
      distribution and transport rate of mitochondria in the processes of cultured
      neuronal cells. Reduced ATP level was also found in the synaptosomal fraction
      isolated from Hdh(CAG)150 knock-in mouse brain. These findings suggest that
      specific N-terminal mutant htt fragments, before the formation of aggregates, can
      impair mitochondrial function directly and that this interaction may be a novel
      target for therapeutic strategies in HD.

PMID- 18337409
TI  - Rapid interactions between the ventral visual stream and emotion-related
      structures rely on a two-pathway architecture.
AB  - Visual attention can be driven by the affective significance of visual stimuli
      before full-fledged processing of the stimuli. Two kinds of models have been
      proposed to explain this phenomenon: models involving sequential processing along
      the ventral visual stream, with secondary feedback from emotion-related
      structures ("two-stage models"); and models including additional short-cut
      pathways directly reaching the emotion-related structures ("two-pathway models").
      We tested which type of model would best predict real magnetoencephalographic
      responses in subjects presented with arousing visual stimuli, using realistic
      models of large-scale cerebral architecture and neural biophysics. The results
      strongly support a "two-pathway" hypothesis. Both standard models including the
      retinotectal pathway and nonstandard models including cortical-cortical long
      range fasciculi appear plausible.

PMID- 18337410
TI  - Adaptive control of saccades via internal feedback.
AB  - Ballistic movements like saccades require the brain to generate motor commands
      without the benefit of sensory feedback. Despite this, saccades are remarkably
      accurate. Theory suggests that this accuracy arises because the brain relies on
      an internal forward model that monitors the motor commands, predicts their
      sensory consequences, and corrects eye trajectory midflight. If control of
      saccades relies on a forward model, then the forward model should adapt whenever
      its predictions fail to match sensory feedback at the end of the movement. Using
      optimal feedback control theory, we predicted how this adaptation should alter
      saccade trajectories. We trained subjects on a paradigm in which the horizontal
      target jumped vertically during the saccade. With training, the final position of
      the saccade moved toward the second target. However, saccades became increasingly
      curved, i.e., suboptimal, as oculomotor commands were corrected on-line to steer
      the eye toward the second target. The adaptive response had two components: (1)
      the motor commands that initiated the saccades changed slowly, aiming the saccade
      closer to the jumped target. The adaptation of these earliest motor commands
      displayed little forgetting during the rest periods. (2) Late in saccade
      trajectory, another adaptive response steered it still closer to the jumped
      target, producing curvature. Adaptation of these late motor commands showed near
      complete forgetting during the rest periods. The two components adapted at
      different timescales, with the late-acting component displaying much faster
      rates. It appears that in controlling saccades, the brain relies on an internal
      feedback that has the characteristics of a fast-adapting forward model.

PMID- 18337411
TI  - Mu-opioid receptor-mediated depression of the hypothalamic hypocretin/orexin
      arousal system.
AB  - Arousal and maintenance of a wake state is dependent on the hypothalamic
      hypocretin/orexin system. We found that hypocretin neurons are depressed by
      opiates, drugs of abuse that reduce cognitive alertness. Met-enkephalin (mENK),
      an endogenous opioid, and exogenous opiates such as morphine inhibited the
      hypocretin system by direct actions on the cell body that include reduced spike
      frequency, hyperpolarization, increased G-protein-coupled inwardly rectifying
      K(+) channel current, and attenuated calcium current, and indirectly through
      reducing excitatory synaptic tone by a presynaptic mechanism. CTAP (H-d-Phe-Cys
      Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2)) and naloxone, antagonists of mu-opioid
      receptors, blocked mu agonist actions. In the absence of exogenous opioids, mu
      receptor antagonists enhanced activity of the hypocretin system, suggesting
      ongoing inhibition by endogenous receptors. Morphine pretreatment attenuated
      subsequent excitatory responses to hypocretin, suggesting a long-lasting
      depression caused by opiate exposure. Chronic exposure to morphine reduced
      subsequent responses to morphine and to mENK, but increased the response to
      opioid receptor antagonists. Together, these data are consistent with the view
      that the hypocretin system may be an important direct target for drugs of abuse,
      including opiates, that induce sedation and mental lethargy.

PMID- 18337412
TI  - Golgi cell dendrites are restricted by Purkinje cell stripe boundaries in the
      adult mouse cerebellar cortex.
AB  - Despite the general uniformity in cellular composition of the adult cerebellar
      cortex, there is a complex underlying pattern of parasagittal stripes of Purkinje
      cells with characteristic molecular phenotypes and patterns of connectivity. It
      is not known whether interneuron processes are restricted at stripe boundaries.
      To begin to address the issue, three strategies were used to explore how
      cerebellar Golgi cell dendrites are organized with respect to parasagittal
      stripes: first, double immunofluorescence staining combining anti-neurogranin to
      identify Golgi cell dendrites with the Purkinje cell compartmentation antigens
      zebrin II/aldolase C, HNK-1, and phospholipase Cbeta4; second, zebrin II
      immunohistochemistry combined with a rapid Golgi-Cox impregnation procedure to
      reveal Golgi cell dendritic arbors; third, stripe antigen expression was used on
      sections of a GlyT2-EGFP transgenic mouse in which reporter expression is
      prominent in Golgi cell dendrites. In each case, the dendritic projections of
      Golgi cells were studied in the vicinity of Purkinje cell stripe boundaries. The
      data presented here show that the dendrites of a cerebellar interneuron, the
      Golgi cell, respect the fundamental cerebellar stripe cytoarchitecture.

PMID- 18337413
TI  - The mitochondrial protease AFG3L2 is essential for axonal development.
AB  - The mitochondrial metalloprotease AFG3L2 assembles with the homologous protein
      paraplegin to form a supracomplex in charge of the essential protein quality
      control within mitochondria. Mutations of paraplegin cause a specific axonal
      degeneration of the upper motoneuron and, therefore, hereditary spastic
      paraplegia. Here we present two Afg3l2 murine models: a newly developed null and
      a spontaneous mutant that we found carrier of a missense mutation. Contrasting
      with the mild and late onset axonal degeneration of paraplegin-deficient mouse,
      Afg3l2 models display a marked impairment of axonal development with delayed
      myelination and poor axonal radial growth leading to lethality at P16. The
      increased severity of the Afg3l2 mutants is explained by two main molecular
      features that differentiate AFG3L2 from paraplegin: its higher neuronal
      expression and its versatile ability to support both hetero-oligomerization and
      homo-oligomerization. Our data assign to AFG3L2 a crucial role by linking
      mitochondrial metabolism and axonal development. Moreover, we propose AFG3L2 as
      an excellent candidate for motoneuron and cerebellar diseases with early onset
      unknown etiology.

PMID- 18337414
TI  - NMDA receptor plasticity in the perirhinal and prefrontal cortices is crucial for
      the acquisition of long-term object-in-place associative memory.
AB  - A key process for recognition memory is the formation of associations between an
      object and the place in which it was encountered, a process that has been shown
      to require the perirhinal (PRH) and medial prefrontal (mPFC) cortices. Here we
      demonstrate, for the first time, the importance of glutamatergic
      neurotransmission, within the PRH and mPFC, for object-in-place associative
      recognition memory. Unilateral blockade of AMPA receptors (by CNQX) in the PRH
      and mPFC in opposite hemispheres impaired an object-in-place task in rats,
      confirming that these cortical regions operate within a neural network for object
      in-place recognition memory. Intra-mPFC infusions of AP5 (NMDA receptor
      antagonist) impaired short-term memory and the acquisition of long-term memory,
      but had no effect on retrieval. AP5 infusions into the PRH disrupted acquisition
      of long-term memory, but not short-term memory or retrieval. Significantly,
      crossed AP5 infusions into both the PRH and mPFC disrupted acquisition of long
      term memory but were without effect on short-term memory. Finally a unilateral
      infusion of the selective kainate (GLU(K5)) receptor antagonist UBP302 [(S)-1-(2
      amino-2-carboxyethyl)-3-(2-carboxybenzyl)pyrimidine-2,4-dione] into the PRH
      combined with a unilateral infusion of AP5 into the contralateral mPFC
      significantly impaired short-term object-in-place associative memory. These data
      show that the PRH and mPFC make distinct contributions to object-in-place
      associative memory and that the encoding of long-term but not short-term memory
      requires concurrent NMDA receptor activation in both cortical regions. In
      contrast, short-term object-in-place memory appears to be dependent on kainate
      receptor activation in the PRH and NMDA receptor activation in the mPFC.

PMID- 18337415
TI  - Directional selectivity in the simple eye of an insect.
AB  - Among other sensory modalities, flight stabilization in insects is performed with
      the aid of visual feedback from three simple eyes (ocelli). It is thought that
      each ocellus acts as a single wide-field sensor that detects changes in light
      intensity. We challenge this notion by providing evidence that, when light
      adapted, the large retinal L-neurons in the median ocellus of the dragonfly
      respond in a directional way to upward moving bars and gratings. This ability is
      pronounced under UV illumination but weak or nonexistent in green light and is
      optimal at angular velocities of approximately 750 degrees s(-1). Using a reverse
      correlation technique, we analyze the functional organization of the receptive
      fields of the L-neurons. Our results reveal that L-neurons alter the structure of
      their linear spatiotemporal receptive fields with changes in the illuminating
      wavelength, becoming more inseparable and directional in UV light than in green.
      For moving bars and gratings, the strength of directionality predicted from the
      receptive fields is consistent with the measured values. Our results strongly
      suggest that, during the day, the retinal circuitry of the dragonfly median
      ocellus performs an early linear stage of motion processing. The likely advantage
      of this computation is to enhance pitch control.

PMID- 18337416
TI  - Neuropathic pain-like behavior after brachial plexus avulsion in mice: the
      relevance of kinin B1 and B2 receptors.
AB  - The relevance of kinin B(1) (B(1)R) and B(2) (B(2)R) receptors in the brachial
      plexus avulsion (BPA) model was evaluated in mice, by means of genetic and
      pharmacological tools. BPA-induced hypernociception was absent in B(1)R, but not
      in B(2)R, knock-out mice. Local or intraperitoneal administration of the B(2)R
      antagonist Hoe 140 failed to affect BPA-induced mechanical hypernociception.
      Interestingly, local or intraperitoneal treatment with B(1)R antagonists, R-715
      or SSR240612, dosed at the time of surgery, significantly reduced BPA-evoked
      mechanical hypernociception. Intrathecal or intracerebroventricular
      administration of these antagonists, at the surgery moment, did not prevent the
      hypernociception. Both antagonists, dosed by intraperitoneal or intrathecal
      routes (but not intracerebroventricularly) 4 d after the surgery, significantly
      inhibited the mechanical hypernociception. At 30 d after the BPA, only the
      intracerebroventricular treatment effectively reduced the hypernociception. A
      marked increase in B(1)R mRNA was observed in the hypothalamus, hippocampus,
      thalamus, and cortex at 4 d after BPA and only in the hypothalamus and cortex at
      30 d. In the spinal cord, a slight increase in B(1)R mRNA expression was observed
      as early as at 2 d. Finally, an enhancement of B(1)R protein expression was found
      in all the analyzed brain structures at 4 and 30 d after the BPA, whereas in the
      spinal cord, this parameter was augmented only at 4 d. The data provide new
      evidence on the role of peripheral and central kinin B(1)R in the BPA model of
      neuropathic pain. Selective B(1)R antagonists might well represent valuable tools
      for the management of neuropathic pain.

PMID- 18337417
TI  - Learning-related plasticity of temporal coding in simultaneously recorded
      amygdala-cortical ensembles.
AB  - Emotional learning requires the coordinated action of neural populations in
      limbic and cortical networks. Here, we performed simultaneous extracellular
      recordings from gustatory cortical (GC) and basolateral amygdalar (BLA) neural
      ensembles as awake, behaving rats learned to dislike the taste of saccharin [via
      conditioned taste aversion (CTA)]. Learning-related changes in single-neuron
      sensory responses were observed in both regions, but the nature of the changes
      was region specific. In GC, most changes were restricted to relatively late
      aspects of the response (starting approximately 1.0 s after stimulus
      administration), supporting our hypothesis that in this paradigm palatability
      related information resides exclusively in later cortical responses. In contrast,
      and consistent with data suggesting the amygdala's primary role in judging
      stimulus palatability, CTA altered all components of BLA taste responses,
      including the earliest. Finally, learning caused dramatic increases in the
      functional connectivity (measured in terms of cross-correlation peak heights)
      between pairs of simultaneously recorded BLA and GC neurons, increases that were
      evident only during taste processing. Our simultaneous assays of the activity of
      single neurons in multiple relevant brain regions across learning suggest that
      the transmission of taste information through amygdala-cortical circuits plays a
      vital role in CTA memory formation.

PMID- 18337418
TI  - Flotillin-dependent clustering of the amyloid precursor protein regulates its
      endocytosis and amyloidogenic processing in neurons.
AB  - The flotillins/reggie proteins are associated with noncaveolar membrane
      microdomains and have been implicated in the regulation of a clathrin- and
      caveolin-independent endocytosis pathway. Endocytosis is required for the
      amyloidogenic processing of the amyloid precursor protein (APP) and thus to
      initiate the release of the neurotoxic beta-amyloid peptide (Abeta), the major
      component of extracellular plaques found in the brains of Alzheimer's disease
      patients. Here, we report that small interference RNA-mediated downregulation of
      flotillin-2 impairs the endocytosis of APP, in both neuroblastoma cells and
      primary cultures of hippocampal neurons, and reduces the production of Abeta.
      Similar to tetanus neurotoxin endocytosis, but unlike the internalization of
      transferrin, clathrin-dependent endocytosis of APP requires cholesterol and
      adaptor protein-2 but is independent of epsin1 function. Moreover, on a nanoscale
      resolution using stimulated emission depletion microscopy and by Forster
      resonance energy transfer with fluorescence lifetime imaging microscopy, we
      provide evidence that flotillin-2 promotes the clustering of APP at the cell
      surface. We show that the interaction of flotillin-2 with APP is dependent on
      cholesterol and that clustering of APP enhances its endocytosis rate. Together,
      our data suggest that cholesterol/flotillin-dependent clustering of APP may
      stimulate the internalization into a specialized clathrin-dependent endocytosis
      pathway to promote amyloidogenic processing.

PMID- 18337419
TI  - Motor adaptation as a process of reoptimization.
AB  - Adaptation is sometimes viewed as a process in which the nervous system learns to
      predict and cancel effects of a novel environment, returning movements to near
      baseline (unperturbed) conditions. An alternate view is that cancellation is not
      the goal of adaptation. Rather, the goal is to maximize performance in that
      environment. If performance criteria are well defined, theory allows one to
      predict the reoptimized trajectory. For example, if velocity-dependent forces
      perturb the hand perpendicular to the direction of a reaching movement, the best
      reach plan is not a straight line but a curved path that appears to
      overcompensate for the forces. If this environment is stochastic (changing from
      trial to trial), the reoptimized plan should take into account this uncertainty,
      removing the overcompensation. If the stochastic environment is zero-mean, peak
      velocities should increase to allow for more time to approach the target.
      Finally, if one is reaching through a via-point, the optimum plan in a zero-mean
      deterministic environment is a smooth movement but in a zero-mean stochastic
      environment is a segmented movement. We observed all of these tendencies in how
      people adapt to novel environments. Therefore, motor control in a novel
      environment is not a process of perturbation cancellation. Rather, the process
      resembles reoptimization: through practice in the novel environment, we learn
      internal models that predict sensory consequences of motor commands. Through
      reward-based optimization, we use the internal model to search for a better
      movement plan to minimize implicit motor costs and maximize rewards.

PMID- 18337420
TI  - P2Y12 receptor upregulation in activated microglia is a gateway of p38 signaling
      and neuropathic pain.
AB  - Microglia in the spinal cord may play an important role in the development and
      maintenance of neuropathic pain. A metabotropic ATP receptor, P2Y(12), has been
      shown to be expressed in spinal microglia constitutively and be involved in
      chemotaxis. Activation of p38 mitogen-activated protein kinase (MAPK) occurs in
      spinal microglia after nerve injury and may be related to the production of
      cytokines and other mediators, resulting in neuropathic pain. However, it remains
      unknown whether any type of P2Y receptor in microglia is involved in the
      activation of p38 MAPK and the pain behaviors after nerve injury. Using the
      partial sciatic nerve ligation (PSNL) model in the rat, we found that P2Y(12)
      mRNA and protein increased in the spinal cord and peaked at 3 d after PSNL.
      Double labeling studies revealed that cells expressing increased P2Y(12) mRNA and
      protein after nerve injury were exclusively microglia. Both pharmacological
      blockades by intrathecal administration of P2Y(12) antagonist and antisense
      knockdown of P2Y(12) expression suppressed the development of pain behaviors and
      the phosphorylation of p38 MAPK in spinal microglia after PSNL. The intrathecal
      infusion of the P2Y(12) agonist 2-(methythio) adenosine 5'-diphosphate trisodium
      salt into naive rats mimicked the nerve injury-induced activation of p38 in
      microglia and elevated pain behaviors. These data suggest a new mechanism of
      neuropathic pain, in which the increased P2Y(12) works as a gateway of the
      following events in microglia after nerve injury. Activation of this receptor by
      released ATP or the hydrolyzed products activate p38 MAPK pathway and may play a
      crucial role in the generation of neuropathic pain.

PMID- 18337421
TI  - Rapid loss of dendritic spines after stress involves derangement of spine
      dynamics by corticotropin-releasing hormone.
AB  - Chronic stress causes dendritic regression and loss of dendritic spines in
      hippocampal neurons that is accompanied by deficits in synaptic plasticity and
      memory. However, the responsible mechanisms remain unresolved. Here, we found
      that within hours of the onset of stress, the density of dendritic spines
      declined in vulnerable dendritic domains. This rapid, stress-induced spine loss
      was abolished by blocking the receptor (CRFR(1)) of corticotropin-releasing
      hormone (CRH), a hippocampal neuropeptide released during stress. Exposure to CRH
      provoked spine loss and dendritic regression in hippocampal organotypic cultures,
      and selective blockade of the CRFR(1) receptor had the opposite effect. Live,
      time-lapse imaging revealed that CRH reduced spine density by altering dendritic
      spine dynamics: the peptide selectively and reversibly accelerated spine
      retraction, and this mechanism involved destabilization of spine F-actin. In
      addition, mice lacking the CRFR(1) receptor had augmented spine density. These
      findings support a mechanistic role for CRH-CRFR(1) signaling in stress-evoked
      spine loss and dendritic remodeling.

PMID- 18337422
TI  - Structural organization of the corpus callosum predicts the extent and impact of
      cortical activity in the nondominant hemisphere.
AB  - Diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI)
      were combined to examine the relationship between callosal organization and
      cortical activity across hemispheres. Healthy young adults performed an
      incidental verbal encoding task (semantic judgments on words) while undergoing
      fMRI. Consistent with previous studies, the verbal encoding task was associated
      with left-lateralized activity in the inferior prefrontal cortex (LIPFC). When
      subjects were divided into two groups based on fractional anisotropy (FA) values
      in the anterior corpus callosum (DTI), individuals with low anterior callosal FA
      were found to exhibit greater activity in a homologous region within the right
      inferior prefrontal cortex (RIPFC) relative to those with high anterior callosal
      FA. Interestingly, whereas the magnitude of RIPFC activity did not negatively
      impact subsequent verbal memory performance for individuals with low anterior
      callosal FA, greater RIPFC activity during verbal encoding was associated with
      poorer subsequent memory performance for individuals with high anterior callosal
      FA. Together, these findings provide novel evidence that individual differences
      in callosal organization are related to the extent of nondominant cortical
      activity during performance during a lateralized task, and further, that this
      relationship has consequences on behavior.

PMID- 18337423
TI  - Functional maturation of the first synapse in olfaction: development and adult
      neurogenesis.
AB  - The first synapse in olfaction undergoes considerable anatomical plasticity in
      both early postnatal development and adult neurogenesis, yet we know very little
      concerning its functional maturation at these times. Here, we used whole-cell
      recordings in olfactory bulb slices to describe olfactory nerve inputs to
      developing postnatal neurons and to maturing adult-born cells labeled with a GFP
      encoding lentivirus. In both postnatal development and adult neurogenesis, the
      maturation of olfactory nerve synapses involved an increase in the relative
      contribution of AMPA over NMDA receptors, and a decrease in the contribution of
      NMDA receptors containing the NR2B subunit. These postsynaptic transformations,
      however, were not mirrored by presynaptic changes: in all cell groups, paired
      pulse depression remained constant as olfactory nerve synapses matured. Although
      maturing cells may therefore offer, transiently, a functionally distinct
      connection for inputs from the nose, presynaptic function at the first olfactory
      connection remains remarkably constant in the face of considerable anatomical
      plasticity.

PMID- 18337424
TI  - Serotonin 5-HT2B receptors are required for 3,4-methylenedioxymethamphetamine
      induced hyperlocomotion and 5-HT release in vivo and in vitro.
AB  - The "club drug" 3,4-methylenedioxymethamphetamine (MDMA; also known as ecstasy)
      binds preferentially to and reverses the activity of the serotonin transporter,
      causing release of serotonin [5-hydroxytryptamine (5-HT)] stores from nerve
      terminals. Subsequent activation of postsynaptic 5-HT receptors by released 5-HT
      has been shown to be critical for the unique psychostimulatory effects of MDMA.
      In contrast, the effects of direct activation of presynaptic and/or postsynaptic
      receptors by MDMA have received far less attention, despite the agonist actions
      of the drug itself at 5-HT(2) receptors, in particular the 5-HT(2B) receptor.
      Here we show that acute pharmacological inhibition or genetic ablation of the 5
      HT(2B) receptor in mice completely abolishes MDMA-induced hyperlocomotion and 5
      HT release in nucleus accumbens and ventral tegmental area. Furthermore, the 5
      HT(2B) receptor dependence of MDMA-stimulated release of endogenous 5-HT from
      superfused midbrain synaptosomes suggests that 5-HT(2B) receptors act, unlike any
      other 5-HT receptor, presynaptically to affect MDMA-stimulated 5-HT release.
      Thus, our findings reveal a novel regulatory component in the actions of MDMA and
      represent the first demonstration that 5-HT(2B) receptors play an important role
      in the brain, i.e., modulation of 5-HT release. As such, 5-HT(2B) receptor
      antagonists may serve as promising therapeutic drugs for MDMA abuse.

PMID- 18337425
TI  - Misplacement of Purkinje cells during postnatal development in Bax knock-out
      mice: a novel role for programmed cell death in the nervous system?
AB  - During early postnatal development, the orchestrated regulation of proliferation,
      migration and the survival versus elimination of neurons is essential for
      histogenesis of the cerebellum. For instance, Purkinje cells (PCs) promote the
      proliferation and migration of external granule cells (EGCs), whereas EGCs in
      turn play a role in the migration of PCs. Considering that a substantial number
      of neurons undergo programmed cell death (PCD) during cerebellar development, it
      seems likely that neuronal loss could have a significant role in the histogenesis
      of the cerebellum. To address this question, we examined postnatal development of
      the cerebellum in Bax-knock-out (KO) mice in which the PCD of PC has been
      reported to be selectively reduced or eliminated, whereas EGCs are unaffected. We
      confirmed the absence of PC PCD as well as the normal PCD of EGCs in Bax-KO mice.
      We also observed a subpopulation of PCs that were misplaced in the inner granule
      cell layer of Bax-KO mice on postnatal day 5 (P5) to P10 and that, by the end of
      the major period of cerebellar histogenesis (P14), lose expression of the PC
      marker calbindin. These results suggest that the removal of ectopically located
      neurons may be a previously unrecognized function of developmental PCD.

PMID- 18337426
TI  - Okadaic acid-sensitive protein phosphatases constrain phrenic long-term
      facilitation after sustained hypoxia.
AB  - Phrenic long-term facilitation (pLTF) is a serotonin-dependent form of pattern
      sensitive respiratory plasticity induced by intermittent hypoxia (IH), but not
      sustained hypoxia (SH). The mechanism(s) underlying pLTF pattern sensitivity are
      unknown. SH and IH may differentially regulate serine/threonine protein
      phosphatase activity, thereby inhibiting relevant protein phosphatases uniquely
      during IH and conferring pattern sensitivity to pLTF. We hypothesized that spinal
      protein phosphatase inhibition would relieve this braking action of protein
      phosphatases, thereby revealing pLTF after SH. Anesthetized rats received
      intrathecal (C4) okadaic acid (25 nm) before SH (25 min, 11% O(2)). Unlike
      (vehicle) control rats, SH induced a significant pLTF in okadaic acid-treated
      rats that was indistinguishable from rats exposed to IH (three 5 min episodes,
      11% O(2)). IH and SH with okadaic acid may elicit pLTF by similar, serotonin
      dependent mechanisms, because intravenous methysergide blocks pLTF in rats
      receiving IH or okadaic acid plus SH. Okadaic acid did not alter IH-induced pLTF.
      In summary, pattern sensitivity in pLTF may reflect differential regulation of
      okadaic acid-sensitive serine/threonine phosphatases; presumably, these
      phosphatases are less active during/after IH versus SH. The specific okadaic acid
      sensitive phosphatase(s) constraining pLTF and their spatiotemporal dynamics
      during and/or after IH and SH remain to be determined.

PMID- 18337427
TI  - Widespread maculopapular rash due to intramuscular interferon beta-1a during the
      treatment of multiple sclerosis.
AB  - We describe a 41-year-old woman with multiple sclerosis, who presented
      erythematous maculopapular rash on the trunk and extremities after the second
      injection of interferon beta-1a. Histopathologic examination of the lesion
      revealed lymphocytic exocytosis and perivascular lymphocytic infiltrate in the
      dermis. Oral antihistamine and topical corticosteroid was started. After
      improvement of the lesions, the third injection was performed. However, the same
      reaction occurred. A prick test, which was performed 6 weeks after the eruption,
      also revealed positive reaction. Although injection-site reactions have been
      observed with interferon beta-1a, to our knowledge there have been no previous
      reports of interferon beta-1a-induced widespread cutaneous reaction.

PMID- 18337428
TI  - Fatigue in multiple sclerosis presenting as acute relapse: subjective and
      objective assessment.
AB  - We report on a patient with multiple sclerosis (MS) who presented with fatigue as
      the only manifestation of an acute MS relapse. Fatigue was assessed by the
      'Wurzburg Fatigue Inventory in MS (WEIMuS)' scale and confirmed by
      neuropsychological testing of attention. After high-dose corticosteroid therapy,
      subjective symptoms were completely abolished. The improvement was corroborated
      by both, the WEIMuS score and neuropsychological testing. MS-related fatigue may
      be the only symptom of an acute MS relapse, and neuropsychological methods may be
      used to objectively assess and follow the time course of this common and
      disabling symptom.

PMID- 18337429
TI  - Evaluating nurse staffing regulation.

PMID- 18337430
TI  - Mandated nurse staffing ratios in California: a comparison of staffing and
      nursing-sensitive outcomes pre- and postregulation.
AB  - This article examines the impact of mandated nursing ratios in California on key
      measures of nursing quality among adults in acute care hospitals. This study is a
      follow-up and extension of our first analysis exploring nurse staffing and
      nursing-sensitive outcomes comparing 2002 pre-ratios regulation data to 2004
      postratios regulation data. For the current study we used postregulation ratios
      data from 2004 and 2006 to assess trends in staffing and outcomes. Findings for
      nurse staffing affirmed the trends noted in 2005 and indicated that changes in
      nurse staffing were consistent with expected increases in the proportion of
      licensed staff per patient. This report includes an exploratory examination of
      the relationship between staffing and nursing-sensitive patient outcomes. However
      anticipated improvements in nursing-sensitive patient outcomes were not observed.
      This report contributes to the growing understanding of the impacts of regulatory
      staffing mandates on hospital operations and patient outcomes.

PMID- 18337431
TI  - Patient safety legislation: a look at health policy development.
AB  - On July 29, 2005, President Bush signed into law the Patient Safety and Quality
      Improvement Act. This long-awaited bill came after considerable debate in the
      Senate and the House that focused on patient safety highlighted by the Institute
      of Medicine's (IOM's) report, To Err Is Human. The IOM report brought the
      significance of patient safety issues to the national forefront and called for
      congressional action, but it was 6 years after that report before Congress passed
      legislation in this area. The article explores the development of patient safety
      legislation and provides a historical review and analysis of the events leading
      to the passage of the final bill. It provides background about the major issues
      requiring resolution and compromise, compares the positions of the competing
      stakeholders, and describes the importance and degree of influence that can
      derive from input by stakeholders in the passage of legislation.

PMID- 18337432
TI  - Public opinion and smoke-free laws.
AB  - Public support for Lexington-Fayette County, Kentucky's smoke-free law,
      perception of health risks from exposure to secondhand smoke (SHS), smoking
      behaviors, and frequency of visiting restaurants, bars, and entertainment venues
      were assessed pre- and post-law. Two cohorts of noninstitutionalized adults (N =
      2,146) were randomly selected and invited to participate in a 10- to 15-min
      telephone survey. Public support for the smoke-free law increased from 56% to
      63%, and respondents were 1.3 times more likely to perceive SHS exposure as a
      health risk after the law took effect. Although adult smoking and home smoking
      policy did not change post-law, adults frequented public venues at least as much
      as before the law. Lexington adults favored the smoke-free legislation despite
      living in a traditionally protobacco climate. The smoke-free law acted as a
      public health intervention as it increased perception of risk of heart disease
      and cancer from SHS exposure.

PMID- 18337433
TI  - Including marginalized populations in HIV clinical trials: a new role for nurse
      researchers.
AB  - This article proposes a new paradigm for nurse-researchers to strengthen
      communication with participants, investigators, and the community in clinical
      trials. The author reviews the current state of HIV vaccine development in
      response to the human and fiscal cost of the HIV epidemic, both in the United
      States and globally. A translational model is proposed for restructuring the
      process by which participants in HIV trials are recruited and the results
      disseminated. Finally, it is proposed that nurses should play a unique and
      essential role in implementing this new model, advocating for individuals,
      strengthening societal trust, and fostering equity.

PMID- 18337434
TI  - Psychiatric nurses' attitudes toward consumer and carer participation in care:
      part 1--exploring the issues.
AB  - Consumer and carer participation in mental health delivery is now enshrined in
      Australian Government policy. However, strategies assisting in implementing this
      vision have not been explored. Nurses are crucial to the mental health workforce,
      both in numbers and by virtue of the therapeutic relationship. The willingness of
      nurses to encourage consumer and carer participation is therefore essential for
      implementation of this policy. This article presents part 1 of the findings of a
      qualitative study exploring nurses' opinions regarding consumer and carer
      participation. Data were analyzed using a content-analysis approach, assisted by
      the software package NVivo. The themes explicated were as follows: Consumer and
      carer participation-a help or a hindrance? Encouragement-an important role for
      nurses; and communication-a gift of nursing. These findings highlight the unique
      and important role nurses can play in encouraging participation and explore some
      of the issues involved if that role is to become a reality.

PMID- 18337435
TI  - Health disparities: what can nursing do?
AB  - Health disparities result from lack of caring within the society. Central to
      nursing, caring makes the profession best suited for leadership in reducing
      disparities. Nursing is losing its capacity for caring. Nursing's progress in
      gaining status has alienated it from the needs of other oppressed groups. It has
      also been seduced by the scientific model and does not always use its best
      judgment of truths about human suffering. Research has identified unequal
      treatment, discrimination, workplace and social status, income inequality, and
      policy decisions to deplete resources as social and economic determinants of
      health. All involve relationships. Nursing is the profession for which
      relationships are primary. Nursing can rebuild the capacity for caring and social
      and relational practice through transforming nursing education on the principle
      of mutuality. Nursing can also promote nurse-managed primary care and focus on
      changing local, state, and national policies to increase access, equity, and
      health protection.

PMID- 18337436
TI  - Parenteral iron with erythropoiesis-stimulating agents for chemotherapy-induced
      anemia.
AB  - PURPOSE: To discuss the clinical issues we addressed in the development of our
      institutional guidelines regarding the assessment of iron stores for cancer- and
      treatment-related anemia and the administration of parenteral iron with
      erythropoiesis-stimulating agents (ESAs). DATA SOURCE: Studies published from
      January 1995 to August 2007 were identified by computer searches of Medline and
      hand searching of bibliographies of the articles identified via the computer
      searches. The current clinical practice guidelines were identified by computer
      searches of the web sites for national professional organizations that represent
      health care professionals who treat patients with cancer. RESULTS: of data
      analysis. Hematopoietic responses demonstrate that epoetin alfa and darbepoetin
      alfa provide similar outcomes for patients with chemotherapy-induced anemia
      (CIA); however, up to 50% of patients receiving these agents fail to adequately
      respond. Functional iron deficiency defined as a state of iron-restricted
      erythropoiesis is likely the primary contributor to the lack of response.
      Hematopoietic responses following ESA therapy with parenteral iron are
      substantially higher compared to response with no or oral iron. CONCLUSIONS: Iron
      stores should be assessed in all patients with cancer- or treatment-related
      anemia and parenteral iron should be administered to patients receiving ESA
      therapy to improve hematopoietic response. A unique algorithm that summarizes our
      institutional guidelines to assess iron stores and administer parenteral iron
      with ESA therapy in patients with CIA is included.

PMID- 18337437
TI  - Evolving roles of oncology pharmacists in Singapore: a survey on prescribing
      patterns of antiemetics for chemotherapy induced nausea and vomiting (CINV) at a
      cancer centre.
AB  - BACKGROUND: National Cancer Centre (NCC) is currently the largest ambulatory
      oncology treatment centre in Singapore that treats mainly solid tumors and
      lymphomas. Oncology pharmacists at NCC play an active role in the management of
      CINV. In order to improve the clinical services delivered by pharmacy,
      particularly in the utilization of antiemetics, pharmacy department conducted a
      survey that aimed to understand the prescribing patterns of antiemetics for CINV.
      OBJECTIVES: ves. The primary aim of this study was to describe medical
      oncologists' perceptions of factors that can influence prescribing of antiemetics
      for acute and delayed nausea and vomiting associated with chemotherapy. A
      secondary aim was to assess medical oncologists' perception of antiemetic
      counseling by oncology pharmacists. METHODS: This was a single-centered, non
      randomized survey conducted at NCC in Singapore. Twenty-seven oncologists in the
      Department of Medical Oncology (DMO) were invited to participate in this survey.
      Survey forms were distributed to the medical oncologists at weekly DMO and tumor
      board meetings in November 2006. RESULTS: Twenty oncologists returned surveys
      during the study period. Most oncologists closely adhered to the institution
      guideline on antiemetics utilization; however, results showed a trend of
      overprescribing acute antiemetics for low emetogenic chemotherapy regimens.
      Oncologists have identified anxiety, age and gender as the top three patient risk
      factors taken into consideration when they prescribe antiemetics. Majority of
      oncologists found pharmacists' counseling on antiemetics to be effective.
      CONCLUSIONS: Through this survey, oncology pharmacists at NCC were able to
      identify areas of antiemetics utilization that needed refinement. Results from
      this survey provide opportunities for oncology pharmacists to collaborate with
      medical oncologists to further improve the management of chemotherapy induced
      nausea and vomiting.

PMID- 18337438
TI  - Comparison of chemotherapy education and patient preferences in community versus
      academic gynecology oncology clinics.
AB  - PURPOSE: To evaluate and compare patients' preferences in receiving chemotherapy
      education from health care teams in community versus academic clinics. METHODS:
      Results from a 13-question questionnaire about the chemotherapy education
      preferences of patients in three community gynecology oncology clinics were
      compared to the results from a similar study previously conducted in an academic
      gynecology oncology clinic. RESULTS: A total of 57% of the 203 community-clinic
      respondents (116) and 67% of the 282 academic-institution respondents (189) who
      completed questionnaires had previously received chemotherapy. Of the patients
      treated in community clinics, almost 60% preferred chemotherapy education to be
      provided in written form and directly by a health care professional compared to
      87% of the patients in academic clinics. Overall, 88% of the patients in the
      community clinics believed they received adequate information, compared to 63% of
      the patients in the academic setting. Patients in the community clinics wanted to
      get more in-depth answers to questions such as 'What is chemotherapy?' (54%) and
      'How it is given?' (55%). In addition, community patients also wanted to know
      more about 'Why chemotherapy stops working?' (72%) and 'What to do and who to
      call about side effects?' (60%). In the academic setting, patients were less
      likely to want to know more about these chemotherapy related questions (42, 35,
      57, and 49, respectively). CONCLUSIONS: Patients preferred to receive written
      chemotherapy education that was reviewed with a healthcare professional and that
      gave more detailed information about the chemotherapeutic drugs themselves and
      how to prevent and manage side effects. As a result of this questionnaire, the
      patient education materials used at our institution will be revised to better
      address patients' preferences in both treatment settings.

PMID- 18337439
TI  - Impact on patient satisfaction with a structured counselling approach on natural
      health products.
AB  - PURPOSE: Natural health products (NHP) are commonly used by cancer patients. The
      provision of better information on NHP may improve the patient satisfaction and
      quality of life. We report the impact on patient satisfaction by routine
      counselling on NHP. METHODS: Patients visiting the pharmacy of a comprehensive
      cancer centre for the first time were recruited before (control) and after
      (intervention) the introduction of routine structured counselling on NHP by
      pharmacists. The primary endpoint was patient satisfaction. Overall cost and cost
      per improvement in satisfaction were estimated. RESULTS: 265 patients completed
      the questionnaires. The average age was about 60 years old, with roughly equal
      number of men and women. Breast and genitor-urinary cancers made up about 80% of
      the patients. Nearly 45% of patients had some college or university education.
      The scores for overall satisfaction and each subscale were all increased in the
      intervention group. This was statistically significant regarding information on
      NHP. Counselling was associated with an increase of about 9 minutes of
      counselling time and a mean additional cost of CDN$7.49 per patient. CONCLUSION:
      We found increased patient satisfaction with routine counselling on NHP. There
      was only minimal increase in workload and cost for each counselling section.

PMID- 18337440
TI  - Efficacy vs. effectiveness--docetaxel and prednisone in hormone refractory
      prostate cancer.
AB  - OBJECTIVES: To assess the clinical effectiveness of docetaxel and prednisone in a
      clinical setting and to compare the results to those seen in the pivotal clinical
      trial. To assess the impact of various factors on the prognosis of patients
      treated with docetaxel. DESIGN: Retrospective chart review. The primary outcome
      measured was survival. Survival data was analyzed through the Kaplan-Meier
      methodology. A multivariate analysis of prognostic variables was also conducted.
      SETTING: Public cancer centers within the Canadian province of Alberta. PATIENTS:
      Hormone refractory, metastatic prostate cancer patients initiated on docetaxel
      chemotherapy between September 2004 and February 2007 within the Alberta Cancer
      Board. Main Outcome Measured. The primary outcome measured was median survival.
      RESULTS: Among 161 patients eligible for review, median survival was 17.22
      months. Chemotherapy received after docetaxel was determined to be a significant
      favorable prognostic factor for survival (p<0.0001). CONCLUSION: In a clinical
      setting, docetaxel and prednisone did not perform as well in terms of median
      survival, as it was shown to in prior clinical trials (17.22 vs. 18.9 months).
      Further investigation into the impact of docetaxel and prednisone on quality of
      life in clinical practice, would complement the findings of this study.

PMID- 18337441
TI  - Successful treatment with etoposide phosphate in patients with previous etoposide
      hypersensitivity.
AB  - OBJECTIVE: To review the experience of treatment with etoposide phosphate in
      patients with acute etoposide hypersensitivity treated in a large tertiary
      referral center hospital specializing in curable malignancies. CASE SUMMARIES:
      The cases of 6 patients with advanced malignancies who experienced acute
      etoposide hypersensitivity are documented. There were 3 male and 3 female
      patients and their ages ranged from 16 to 68. Four patients had curable
      malignancies with trophoblast tumors or germ cell tumors and two were receiving
      palliative chemotherapy for other malignancies. All of the 6 patients who
      experienced etoposide hypersensitivity developed their symptoms in the first few
      minutes of the initial infusion. The most common symptoms were chest pain, facial
      flushing, and bronchospasm. All of the patients had emergency treatment with
      discontinuation of the infusion and usually the administration of hydrocortisone
      and chlorpheniramine, which lead to the rapid resolution of their symptoms. For
      the next cycle of chemotherapy each patient was rechallenged with etoposide
      phosphate, with steroid cover given in only two of the cases. None of the 6
      patients experienced any hypersensitivity symptoms on treatment with etoposide
      phosphate and in one the steroids were withdrawn for all the subsequent cycles.
      The 4 patients with curable malignancies all remain disease free, while the 2
      palliative patients obtained significant control of their disease. DISCUSSION:
      Etoposide is one of the most important chemotherapy drugs in the treatment of
      many curable malignancies but an acute hypersensitivity reaction occurs in around
      1% of patients. Retreatment with etoposide in these patients is difficult and
      generally alternative drugs/regimens have to be used. A small number of case
      reports have suggested that etoposide phosphate can be safely used in these
      patients and 6 cases have been found in the pharmacy records where this has been
      done. In all of the patients, treatment with etoposide phosphate proceeded
      without any symptoms or the use of repeated steroid cover in 5 of the 6 patients.
      CONCLUSION: Etoposide hypersensitivity is a rare clinical problem and responds
      promptly to drug discontinuation, steroids, and chlorpheniramine. Patients with
      previous etoposide hypersensitivity can safely be treated with etoposide
      phosphate and do not need any additional hypersensitivity prophylaxis.

PMID- 18337442
TI  - A fatal outcome in a patient with glioblastoma multiforme after receiving high
      dose methotrexate.
AB  - The most common adult primary brain tumor is glioblastoma multiforme (GBM).
      Current treatment is surgical resection, adjuvant radiation and chemotherapy,
      which can extend the median survival 20-36 weeks (Mansky et al. Central nervous
      system tumors. In Abraham J, Allegra CJ, Gulley J, eds. Bethesda Handbook of
      clinical oncology, 2nd edn. Philadelphia, Pennsylvania: Lippincott Williams and
      Wilkins, 2000: 440-2; Knox S. Intracranial tumors. In Pillot G, Chantler M,
      Magiera H, Peles S, et al., eds. The Washington Manual Hematology and Oncology
      Subspecialty Consult. Philadelphia, Pennsylvania: Lippincott Williams and
      Wilkins, 2004: 204-6.). But treatment efficacy is limited, mandating the
      exploration of more effective treatments. We report on a patient with GBM treated
      as per a clinical protocol with high-dose methotrexate (12 g/m(2)), who expired
      within hours after the initiation of treatment secondary to transtentorial
      herniation. Although it is not completely clear what caused the patient's
      herniation, we think that high-dose methotrexate therapy may have played a
      crucial role. We suggest that high-dose methotrexate should be used cautiously in
      patients with GBM.

PMID- 18337443
TI  - Hydroxyurea induced acute elevations in liver function tests.
AB  - Hydroxyurea (HU) is a ribonucleotide reductase inhibitor used to treat
      myeloproliferative diseases including polycythemia vera (PV) and essential
      thrombocythemia (ET). We describe an 82-year-old male who was started on HU 500
      mg three times weekly for the treatment of PV. Eight days after initiation of HU
      he experienced anorexia, nausea, vomiting, fever, fatigue, dizziness, and shaking
      chills. Discontinuation of the HU resulted in resolution of his symptoms within 2
      days, and HU was re-started. Ten days after re-starting HU, the patient re
      presented with nausea and anorexia. Lab tests revealed elevations in liver enzyme
      function tests, which resolved promptly after cessation of HU. Patients being
      initiated on HU should be advised that rarely, fevers, chills, nausea, and
      elevations in liver function tests may occur.

PMID- 18337444
TI  - Distinct functionality of tumor cell-derived gelatinases during formation of
      liver metastases.
AB  - The specific spatiotemporal role of the matrix metalloproteinase 2 (MMP-2) and
      MMP-9 (gelatinase) during metastasis is still under debate. Host cells have been
      described as major contributors to these MMPs during metastasis. Here, we show
      strong overexpression of MMP-2 and MMP-9 by tumor cells of clinical liver
      specimen of recurrent metachronous metastases, leading us to address the
      importance of tumor cell-derived MMP-2 or MMP-9 during liver metastasis. Thus
      far, distinction of their roles was impossible due to lack of inhibitors which
      can act exclusively on tumor cells or distinguish MMP-2 from MMP-9. We therefore
      used short hairpin RNA interference technology in the well-established syngeneic
      L-CI.5s lymphoma model, in which we could analyze the time course of experimental
      liver colonization (arrest/invasion of single tumor cells, outgrowth, and
      invasion within the parenchyma) in immunocompetent mice and correlate these steps
      with MMP-2 or MMP-9 expression levels. In parental tumor cells, MMP-9 expression
      closely correlated with the invasive phases of liver colonization, whereas MMP-2
      expression remained unaltered. Specific knockdown of MMP-9 revealed a close
      correlation between invasion-dependent events and tumor cell-derived MMP-9
      expression. In contrast, knockdown of MMP-2 did not significantly alter the
      metastatic potential of the cells but led to a marked inhibition of metastatic
      foci growth. These findings explain the efficacy of gelatinase-specific synthetic
      inhibitors on invasion and growth of tumor cells and attribute distinct functions
      of MMP-2 and MMP-9 to aspects of liver metastasis.

PMID- 18337445
TI  - Positive feedback between vascular endothelial growth factor-A and autotaxin in
      ovarian cancer cells.
AB  - Tumor cell migration, invasion, and angiogenesis are important determinants of
      tumor aggressiveness, and these traits have been associated with the motility
      stimulating protein autotaxin (ATX). This protein is a member of the
      ectonucleotide pyrophosphatase and phosphodiesterase family of enzymes, but
      unlike other members of this group, ATX possesses lysophospholipase D activity.
      This enzymatic activity hydrolyzes lysophosphatidylcholine to generate the potent
      tumor growth factor and motogen lysophosphatidic acid (LPA). In the current
      study, we show a link between ATX expression, LPA, and vascular endothelial
      growth factor (VEGF) signaling in ovarian cancer cell lines. Exogenous addition
      of VEGF-A to cultured cells induces ATX expression and secretion, resulting in
      increased extracellular LPA production. This elevated LPA, acting through LPA(4),
      modulates VEGF responsiveness by inducing VEGF receptor (VEGFR)-2 expression.
      Down-regulation of ATX secretion in SKOV3 cells using antisense morpholino
      oligomers significantly attenuates cell motility responses to VEGF, ATX, LPA, and
      lysophosphatidylcholine. These effects are accompanied by decreased LPA(4) and
      VEGFR2 expression as well as by increased release of soluble VEGFR1. Because LPA
      was previously shown to increase VEGF expression in ovarian cancer, our data
      suggest a positive feedback loop involving VEGF, ATX, and its product LPA that
      could affect tumor progression in ovarian cancer cells.

PMID- 18337446
TI  - Host nuclear factor-kappaB activation potentiates lung cancer metastasis.
AB  - Epidemiologic and experimental evidence suggests that a link exists between
      inflammation and cancer, although this relationship has only recently begun to be
      elucidated for lung cancer, the most frequently fatal human tumor. Nuclear factor
      kappaB (NF-kappaB), a transcription factor that controls innate immune responses
      in the lungs, has been implicated as an important determinant of cancer cell
      proliferative and metastatic potential; however, its role in lung tumorigenesis
      is uncertain. Here, we specifically examine the role of NF-kappaB-induced airway
      inflammation in lung cancer metastasis using a model of intravenous injection of
      Lewis lung carcinoma cells into immunocompetent C57Bl/6 mice. Induction of lung
      inflammation by direct and specific NF-kappaB activation in airway epithelial
      cells potentiates lung adenocarcinoma metastasis. Moreover, we identify resident
      lung macrophages as crucial effectors of lung susceptibility to metastatic cancer
      growth. We conclude that NF-kappaB activity in host tissue is a significant
      factor in the development of lung metastasis.

PMID- 18337447
TI  - Enhanced expression of Rab27A gene by breast cancer cells promoting invasiveness
      and the metastasis potential by secretion of insulin-like growth factor-II.
AB  - In addition to the functions of transporting melanosome in melanocytes and
      releasing contents of lytic granules in CTLs, Rab27A was recently shown to be
      involved in exocytosis of insulin and chromaffin granules in endocrine cells; it
      was also reported to be expressed in an exceptionally broad range of specialized
      secretory cells. As autocrine and paracrine cytokines are essential for invasion
      and metastasis in some solid tumors, blocking them may be an effective strategy
      to prevent tumor dissemination. In the present study, we show that Rab27A is
      associated with invasive and metastatic potentials of human breast cancer cells.
      The overexpression of Rab27A protein redistributed the cell cycle and increased
      the invasive and metastatic abilities in breast cancer cells both in vitro and in
      vivo. We also certified that Rab27A conferred the invasive and metastatic
      phenotypes on breast cancer cells by promoting the secretion of insulin-like
      growth factor-II (IGF-II), which regulates the expression of p16, vascular
      endothelial growth factor, matrix metalloproteinase-9, cathepsin D, cyclin D1,
      and urokinase-type plasminogen activator. These data provide functional evidence
      that Rab27A acts as a novel mediator of invasion and metastasis promotion in
      human breast cancer cells, at least in part, through regulating the secretion of
      IGF-II, suggesting that synergistic suppression of Rab27A and IGF-II activities
      holds a promise for preventing breast cancer invasion and metastasis.

PMID- 18337448
TI  - Glioma regression in vitro and in vivo by a suicide combined treatment.
AB  - We present here a suicide therapy against malignant gliomas based on the transfer
      to tumor cells of a gene encoding a beta-glucosidase, linamarase (lis), which in
      the presence of the innocuous substrate linamarin (lin) produces cyanide,
      blocking the mitochondrial respiratory chain. Dog glioma cells carrying the lis
      gene are thus sensitive to lin (IC(50) of 250 microg/mL at 48 hours) and cell
      death is accompanied by mitochondrial fission and ATP depletion. The combination
      of lis/lin with an otherwise nontoxic level of glucose oxidase (GO) enhances the
      therapeutic potential (IC(50) of 50 microg/mL at 48 hours). GO produces hydrogen
      peroxide, inducing oxidative damage and increasing cellular stress. We show here
      the antitumoral effect of the lis/lin/GO therapy in a canine glioma cell line and
      in a xenograft glioma model in nude mice. The synergic combination causes
      mitochondrial membrane depolarization and phosphatidylserine externalization and
      accelerates death by 48 hours. The lethal process is caspase independent;
      poly(ADP-ribose) polymerase 1 is not implicated; and there is no apoptosis
      inducing factor translocation to the nucleus. The combined system induces
      autophagic cell death that can be rescued by 3-methyladenine and is characterized
      by the presence of double-membrane vesicles and punctate LC-3 pattern.

PMID- 18337449
TI  - Epidermal growth factor receptor vIII expression in U87 glioblastoma cells alters
      their proteasome composition, function, and response to irradiation.
AB  - Little is known about the factors that influence the proteasome structures in
      cells and their activity, although this could be highly relevant to cancer
      therapy. We have previously shown that, within minutes, irradiation inhibits
      substrate degradation by the 26S proteasome in most cell types. Here, we report
      an exception in U87 glioblastoma cells transduced to express the epidermal growth
      factor receptor vIII (EGFRvIII) mutant (U87EGFRvIII), which does not respond to
      irradiation with 26S proteasome inhibition. This was assessed using either a
      fluorogenic substrate or a reporter gene, the ornithine decarboxylase degron
      fused to ZsGreen (cODCZsGreen), which targets the protein to the 26S proteasome.
      To elucidate whether this was due to alterations in proteasome composition, we
      used quantitative reverse transcription-PCR to quantify the constitutive (X, Y,
      Z) and inducible 20S subunits (Lmp7, Lmp2, Mecl1), and 11S (PA28alpha and beta)
      and 19S components (PSMC1 and PSMD4). U87 and U87EGFRvIII significantly differed
      in expression of proteasome subunits, and in particular immunosubunits.
      Interestingly, 2 Gy irradiation of U87 increased subunit expression levels by 16%
      to 324% at 6 hours, with a coincident 30% decrease in levels of the proteasome
      substrate c-myc, whereas they changed little in U87EGFRvIII. Responses similar to
      2 Gy were seen in U87 treated with a proteasome inhibitor, NPI0052, suggesting
      that proteasome inhibition induced replacement of subunits independent of the
      means of inhibition. Our data clearly indicate that the composition and function
      of the 26S proteasome can be changed by expression of the EGFRvIII. How this
      relates to the increased radioresistance associated with this cell line remains
      to be established.

PMID- 18337450
TI  - Involvement of fibroblast growth factor receptor 2 isoform switching in mammary
      oncogenesis.
AB  - We identified the IIIb C2 epithelial cell-specific splice variant of fibroblast
      growth factor receptor 2 (FGFR2 IIIb C2) receptor tyrosine kinase in a screen for
      activated oncogenes expressed in T-47D human breast carcinoma cells. We found
      FGFR2 IIIb C2 expression in breast carcinoma cell lines and, additionally,
      expression of the mesenchymal-specific FGFR2 IIIc splice variant in invasive
      breast carcinomas. FGFR2 IIIc expression was associated with loss of epithelial
      markers and gain of mesenchymal markers. Although FGFR2 IIIb is expressed in
      epithelial cells, previous studies on FGFR2 IIIb transformation have focused on
      NIH 3T3 fibroblasts. Therefore, we compared the transforming activities of FGFR2
      IIIb C2 in RIE-1 intestinal cells and several mammary epithelial cells. FGFR2
      IIIb C2 caused growth transformation of epithelial cells but morphologic
      transformation of only NIH 3T3 cells. FGFR2 IIIb C2-transformed NIH 3T3, but not
      RIE-1 cells, showed persistent activation of Ras and increased cyclin D1 protein
      expression. NIH 3T3 but not RIE-1 cells express keratinocyte growth factor, a
      ligand for FGFR2 IIIb C2. Ectopic treatment with keratinocyte growth factor
      caused FGFR2 IIIb C2-dependent morphologic transformation of RIE-1 cells, as well
      as cyclin D1 up-regulation, indicating that both ligand-independent and stromal
      cell-derived, ligand-dependent mechanisms contribute to RIE-1 cell
      transformation. Our results support cell context distinct mechanisms of FGFR2
      IIIb C2 transformation.

PMID- 18337451
TI  - CXCL12/CXCR4 transactivates HER2 in lipid rafts of prostate cancer cells and
      promotes growth of metastatic deposits in bone.
AB  - Chemokines and their receptors function in migration and homing of cells to
      target tissues. Recent evidence suggests that cancer cells use a chemokine
      receptor axis for metastasis formation at secondary sites. Previously, we showed
      that binding of the chemokine CXCL12 to its receptor CXCR4 mediated signaling
      events resulting in matrix metalloproteinase-9 expression in prostate cancer bone
      metastasis. A variety of methods, including lipid raft isolation, stable
      overexpression of CXCR4, cellular adhesion, invasion assays, and the severe
      combined immunodeficient-human bone tumor growth model were used. We found that
      (a) CXCR4 and HER2 coexist in lipid rafts of prostate cancer cells; (b) the
      CXCL12/CXCR4 axis results in transactivation of the HER2 receptor in lipid rafts
      of prostate cancer cells; (c) Src kinase mediates CXCL12/CXCR4 transactivation of
      HER2 in prostate cancer cells; (d) a pan-HER inhibitor desensitizes CXCR4-induced
      transactivation and subsequent matrix metalloproteinase-9 secretion and invasion;
      (e) lipid raft-disrupting agents inhibited raft-associated CXCL12/CXCR4
      transactivation of the HER2 and cellular invasion; (f) overexpression of CXCR4 in
      prostate cancer cells leads to increased HER2 phosphorylation and migratory
      properties of prostate cancer cells; and (g) CXCR4 overexpression enhances bone
      tumor growth and osteolysis. These data suggest that lipid rafts on the cell
      membrane are the key site for CXCL12/CXCR4-induced HER2 receptor transactivation.
      This transactivation contributes to enhanced invasive signals and metastatic
      growth in the bone microenvironment.

PMID- 18337452
TI  - The critical role of the colony-stimulating factor-1 receptor in the
      differentiation of myeloblastic leukemia cells.
AB  - How diverse stimuli control hemopoietic lineage development is unknown. An early
      event during induction of macrophage differentiation in the myeloblastic leukemia
      M1 cell line by different stimuli, such as leukemia inhibitory factor (LIF) and
      interleukin-6 (IL-6), is expression of the colony-stimulating factor-1 receptor
      (CSF-1R). We report that expression of active CSF-1R in M1 cells accelerated
      their subsequent terminal differentiation into macrophages in response to LIF and
      IL-6 when compared with cells lacking the CSF-1R or expressing the receptor with
      compromised kinase activity; however, there was no requirement for signaling
      through the CSF-1R, for example, via endogenous CSF-1, during the actual LIF
      induced and IL-6-induced differentiation stage. Differences were noted in the
      signaling pathways downstream of the LIF receptor depending on the presence of
      the CSF-1R. Both LIF and IL-6 gave an additive response with CSF-1, consistent
      with LIF and IL-6 acting via a different signaling pathway (signal transducer and
      activator of transcription 3 dependent) than CSF-1 (extracellular signal
      regulated kinase dependent). Based at least on this cell model, we propose that
      terminal macrophage differentiation involves a critical priming or deterministic
      phase in which signaling by the CSF-1R prepares a precursor population for
      subsequent rapid terminal macrophage differentiation by diverse stimuli. We also
      propose that expression and activation of the CSF-1R explain much prior
      literature on macrophage lineage commitment in M1 leukemic cells and may be
      important in controlling the progression of certain myeloid leukemias.

PMID- 18337453
TI  - Modulation of endocrine pancreas development but not beta-cell carcinogenesis by
      Sprouty4.
AB  - Sprouty (Spry) proteins modulate signal transduction pathways elicited by
      receptor tyrosine kinases (RTK). Depending on cell type and the particular RTK,
      Spry proteins exert dual functions: They can either repress RTK-mediated
      signaling pathways, mainly by interfering with the Ras/Raf/mitogen-activated
      protein kinase pathway or sustaining RTK signal transduction, for example by
      sequestering the E3 ubiquitin-ligase c-Cbl and thus preventing ubiquitylation,
      internalization, and degradation of RTKs. Here, by the inducible expression of
      murine Spry4 in pancreatic beta cells, we have assessed the functional role of
      Spry proteins in the development of pancreatic islets of Langerhans in normal
      mice and in the Rip1Tag2 transgenic mouse model of beta-cell carcinogenesis. beta
      cell-specific expression of mSpry4 provokes a significant reduction in islet
      size, an increased number of alpha cells per islet area, and impaired islet cell
      type segregation. Functional analysis of islet cell differentiation in cultured
      PANC-1 cells shows that mSpry4 represses adhesion and migration of
      differentiating pancreatic endocrine cells, most likely by affecting the
      subcellular localization of the protein tyrosine phosphatase PTP1B. In contrast,
      transgenic expression of mSpry4 during beta-cell carcinogenesis does not
      significantly affect tumor outgrowth and progression to tumor malignancy. Rather,
      tumor cells seem to escape mSpry4 transgene expression.

PMID- 18337454
TI  - Metallothionein induction by hypoxia involves cooperative interactions between
      metal-responsive transcription factor-1 and hypoxia-inducible transcription
      factor-1alpha.
AB  - Mammalian metallothionein (MT) genes are transcriptionally activated by the
      essential metal zinc as well as by environmental stresses, including toxic metal
      overload and redox fluctuations. In addition to playing a key role in zinc
      homeostasis, MT proteins can protect against metal- and oxidant-induced cellular
      damage, and may participate in other fundamental physiologic and pathologic
      processes such as cell survival, proliferation, and neoplasia. Previously, our
      group reported a requirement for metal-responsive transcription factor-1 (MTF-1)
      in hypoxia-induced transcription of mouse MT-I and human MT-IIA genes. Here, we
      provide evidence that the protumorigenic hypoxia-inducible transcription factor
      1alpha (HIF-1alpha) is essential for induction of MT-1 by hypoxia, but not zinc.
      Chromatin immunoprecipitation assays revealed that MTF-1 and HIF-1alpha are both
      recruited to the mouse MT-I promoter in response to hypoxia, but not zinc. In the
      absence of HIF-1alpha, MTF-1 is recruited to the MT-I promoter but fails to
      activate MT-I gene expression in response to hypoxia. Thus, HIF-1alpha seems to
      function as a coactivator of MT-I gene transcription by interacting with MTF-1
      during hypoxia. Coimmunoprecipitation studies suggest interaction between MTF-1
      and HIF-1alpha, either directly or as mediated by other factors. It is proposed
      that association of these important transcription factors in a multiprotein
      complex represents a common strategy to control unique sets of hypoxia-inducible
      genes in both normal and diseased tissue.

PMID- 18337455
TI  - Geldanamycin-induced down-regulation of ErbB2 from the plasma membrane is
      clathrin dependent but proteasomal activity independent.
AB  - ErbB2, a member of the epidermal growth factor receptor family, is overexpressed
      in a number of human cancers. In contrast to the epidermal growth factor
      receptor, ErbB2 is normally endocytosis resistant. However, ErbB2 can be down
      regulated by inhibitors of heat shock protein 90, such as geldanamycin. We now
      show that geldanamycin induces endocytosis and lysosomal degradation of full
      length ErbB2. We further report that the endocytosis of ErbB2 is dynamin and
      clathrin dependent. When ErbB2 was retained at the plasma membrane due to
      knockdown of clathrin heavy chain, the intracellular part of ErbB2 was degraded
      in a proteasomal manner. However, our data strongly suggest that proteasomal
      activity is not required for geldanamycin-induced endocytosis of ErbB2 in SKBr3
      cells. Interestingly, however, proteasomal inhibitors retarded degradation of
      ErbB2, and electron microscopy analysis strongly suggested that proteasomal
      activity is required to sort internalized ErbB2 to lysosomes. Because
      geldanamycin derivatives and inhibitors of proteasomal activity are both used in
      experimental cancer treatment, knowledge of molecular mechanisms involved in
      geldanamycin-induced down-regulation of ErbB2 is important for future design of
      cancer treatment.

PMID- 18337456
TI  - Mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase kinase 1
      protein expression is subject to translational regulation in prostate cancer cell
      lines.
AB  - Mitogen-activated protein kinase kinase 4/c-Jun NH(2)-terminal kinase kinase 1
      (MKK4/JNKK1; hereafter referred to as MKK4) is a dual-specificity kinase with a
      critical role in regulating the activity of c-Jun NH(2)-terminal kinase and p38
      kinases. We identified a novel biological function for MKK4 in the regulation of
      growth of ovarian and prostate cancer metastases. Clinical correlative studies
      showed that MKK4 protein levels were reduced in high-grade prostate cancer and
      prostate and ovarian cancer metastases compared with normal tissue, which
      prompted investigation into the mechanism(s) responsible for down-regulation of
      MKK4 in a panel of cancer cell lines. Initial studies found that low levels of
      MKK4 protein did not correlate with either exon deletion or decreased levels of
      MKK4 mRNA, suggesting that MKK4 protein levels were regulated
      posttranscriptionally by either reduced translation or reduced protein stability.
      Endogenous MKK4 was highly stable and not subject to altered proteolysis.
      Instead, MKK4 biosynthesis seemed to be regulated by altered translation. In
      support of this assertion, we found that cytosolic MKK4 mRNA was shifted toward
      active polysomes in cells with higher levels of MKK4 protein, suggesting that
      MKK4 mRNA was translated more efficiently in these cells. This study supports a
      novel mechanism for the regulation of MKK4 protein levels. Further, these
      findings have potential therapeutic implications for modulating the expression of
      a signaling kinase involved in the regulation of metastatic growth.

PMID- 18337457
TI  - Cripto-1 alters keratinocyte differentiation via blockade of transforming growth
      factor-beta1 signaling: role in skin carcinogenesis.
AB  - Cripto-1 is an epidermal growth factor-Cripto/FRL1/Cryptic family member that
      plays a role in early embryogenesis as a coreceptor for Nodal and is
      overexpressed in human tumors. Here we report that in the two-stage mouse skin
      carcinogenesis model, Cripto-1 is highly up-regulated in tumor promoter-treated
      normal skin and in benign papillomas. Treatment of primary mouse keratinocytes
      with Cripto-1 stimulated proliferation and induced expression of keratin 8 but
      blocked induction of the normal epidermal differentiation marker keratin 1,
      changes that are hallmarks of tumor progression in squamous cancer. Chemical or
      genetic blockade of the transforming growth factor (TGF)-beta1 signaling pathway
      using the ALK5 kinase inhibitor SB431542 and dominant negative TGF-beta type II
      receptor, respectively, had similar effects on keratinocyte differentiation. Our
      results show that Cripto-1 could block TGF-beta1 receptor binding,
      phosphorylation of Smad2 and Smad3, TGF-beta-responsive luciferase reporter
      activity, and TGF-beta1-mediated senescence of keratinocytes. We suggest that
      inhibition of TGF-beta1 by Cripto-1 may play an important role in altering the
      differentiation state of keratinocytes and promoting outgrowth of squamous tumors
      in the mouse epidermis.

PMID- 18337458
TI  - A unique glycosyltransferase involved in the initial assembly of Moraxella
      catarrhalis lipooligosaccharides.
AB  - Moraxella catarrhalis express three predominant forms of lipooligosaccharide
      (LOS) molecules on the bacterial surface. These major glycolipids contain
      specific carbohydrate epitopes that distinguish each glycoform into serotype A,
      B, or C LOS. All three serotypes, however, share a common glucose containing
      inner-core structure, consisting of an alpha-glucose attached to 2-keto-3
      deoxyoctulosonic acid (KDO), which is unique among Gram-negative bacteria. Many
      of the LOS glycosyltransferase genes (lgt) responsible for assembly of the
      extended M. catarrhalis LOS structure have been identified. In this report, we
      now describe the identification and characterization of Lgt6, a unique
      glycosyltransferase that is responsible for the addition of the first glucose to
      the inner core thus initiating the assembly of full length LOS. Isogenic mutants
      defective in the expression of lgt6 were constructed in all three M. catarrhalis
      LOS serotypes and the resulting LOS glycoforms consisted of KDO(2)-lipid A-OH as
      analyzed by urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE) and mass spectrometry. In addition, the expression of lgt6 in trans in a
      heptose-deficient Neisseria meningitidis NMB gmhX mutant resulted in the addition
      of a hexose to the LOS of this strain. These studies demonstrate that Lgt6
      functions as an alpha-(1-5)-glucosyltransferase in M. catarrhalis adding the
      primary glucose to the KDO(2)-lipid A-OH in LOS biosynthesis. The function of
      Lgt6 is required for the completion of both the major and minor oligosaccharide
      chains in M. catarrhalis.

PMID- 18337459
TI  - Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and
      function in airway smooth muscle.
AB  - Chronic use of inhaled beta-agonists by asthmatics is associated with a loss of
      bronchoprotective effect and deterioration of asthma control. Beta-agonist
      promoted desensitization of airway smooth muscle beta-2-adrenergic receptors,
      mediated by G protein-coupled receptor kinases and arrestins, is presumed to
      underlie these effects, but such a mechanism has never been demonstrated. Using
      in vitro, ex vivo, and in vivo murine models, we demonstrate that beta-arrestin-2
      gene ablation augments beta-agonist-mediated airway smooth muscle relaxation,
      while augmenting beta-agonist-stimulated cyclic adenosine monophosphate
      production. In cultures of human airway smooth muscle, small interfering RNA
      mediated knockdown of arrestins also augments beta-agonist-stimulated cyclic
      adenosine monophosphate production. Interestingly, signaling and function
      mediated by m2/m3 muscarinic acetylcholine receptors or prostaglandin E(2)
      receptors were not affected by either beta-arrestin-2 knockout or arrestin
      knockdown. Thus, arrestins are selective regulators of beta-2-adrenergic receptor
      signaling and function in airway smooth muscle. These results and our previous
      findings, which demonstrate a role for arrestins in the development of allergic
      inflammation in the lung, identify arrestins as potentially important therapeutic
      targets for obstructive airway diseases.

PMID- 18337460
TI  - The glucose-6-phosphate transporter is a phosphate-linked antiporter deficient in
      glycogen storage disease type Ib and Ic.
AB  - Glycogen storage disease type Ib (GSD-Ib) is caused by deficiencies in the
      glucose-6-phosphate (G6P) transporter (G6PT) that have been well characterized.
      Interestingly, deleterious mutations in the G6PT gene were identified in clinical
      cases of GSD type Ic (GSD-Ic) proposed to be deficient in an inorganic phosphate
      (P(i)) transporter. We hypothesized that G6PT is both the G6P and P(i)
      transporter. Using reconstituted proteoliposomes we show that both G6P and P(i)
      are efficiently taken up into P(i)-loaded G6PT-proteoliposomes. The G6P uptake
      activity decreases as the internal:external P(i) ratio decreases and the P(i)
      uptake activity decreases in the presence of external G6P. Moreover, G6P or P(i)
      uptake activity is not detectable in P(i)-loaded proteoliposomes containing the
      p.R28H G6PT null mutant. The G6PT-proteoliposome-mediated G6P or P(i) uptake is
      inhibited by cholorgenic acid and vanadate, both specific G6PT inhibitors.
      Glucose-6-phosphatase-alpha (G6Pase-alpha), which facilitates microsomal G6P
      uptake by G6PT, fails to stimulate G6P uptake in P(i)-loaded G6PT
      proteoliposomes, suggesting that the G6Pase-alpha-mediated stimulation is caused
      by decreasing G6P and increasing P(i) concentrations in microsomes. Taken
      together, our results suggest that G6PT has a dual role as a G6P and a P(i)
      transporter and that GSD-Ib and GSD-Ic are deficient in the same G6PT gene.

PMID- 18337461
TI  - The endoplasmic reticulum-Golgi pathway is a target for translocation and
      aggregation of mutant superoxide dismutase linked to ALS.
AB  - Mutations in superoxide dismutase 1 (SOD1) are responsible for 20% cases of
      familial amyotrophic lateral sclerosis (ALS). However, the mechanism of motor
      neuron degeneration caused by ALS-linked SOD1 mutants is not fully understood.
      Here, we used novel live cell imaging techniques to demonstrate the subcellular
      localization of EGFP-fused SOD1 of both wild-type (WT) and ALS-linked mutant
      forms in the endoplasmic reticulum (ER) and Golgi. The presence of WT and mutant
      SOD1 species in luminal structures was further confirmed by immunoblotting
      analysis of microsomal fractions from spinal cord lysates of SOD1 transgenic mice
      prepared by sucrose density-gradient ultracentrifugation. Chemical cross-linking
      studies also revealed an age-dependent aggregation of mutant SOD1, but not of WT
      SOD1, prominently in the microsomal fraction. Cell-free translocation assays
      provided evidence that monomeric SOD1 is a molecular form that can be
      translocated into luminal structures in the presence of ATP. Our finding that the
      ER-Golgi pathway is a predominant cellular site of aggregation of mutant SOD1
      suggests that secretion could play a key role in pathogenesis, which is in line
      with the view that the disease is non-cell autonomous.

PMID- 18337462
TI  - When the child has a fever.
AB  - Fever in a child is usually due to a self-limiting viral infection, with recovery
      occurring quickly without intervention. However, fever may also be the presenting
      feature of severe illnesses such as meningitis, septicaemia, urinary tract
      infections and pneumonia, and trying to exclude such causes is a key part of
      management. In a review 17 years ago, we concluded that there was no evidence
      that reducing fever improved the outcome of childhood infections, but that it
      probably alleviated distress and discomfort caused by fever. We also advised that
      parents should give paracetamol only if the child seemed uncomfortable or had
      previously had a febrile convulsion, and said that tepid sponging may further
      comfort the child, while recognising evidence that it added little to the effect
      of paracetamol alone. Does this advice still hold?

PMID- 18337463
TI  - Risks of extended-spectrum beta-lactamases.
AB  - Extended-spectrum beta-lactamases (ESBLs) are an increasingly important cause of
      multi-drug resistant infections throughout the world.1,2 Bacteria carrying such
      enzymes have long been recognised as a cause of healthcare-associated infection.3
      However, of concern, the incidence of such organisms also appears to be
      increasing in the community, typically as a cause of urinary tract infection.1,4
      Infections due to ESBL-producing organisms can pose a major threat to life; are
      often difficult and expensive to treat; and can delay discharge from hospital.5(
      )8 Here we discuss the bacteria that produce ESBLs and treatment of patients who
      are infected with such organisms.

PMID- 18337464
TI  - Elaboration: diabetes and driving.

PMID- 18337465
TI  - A novel protein phosphatase is a binding partner for the protein kinase domains
      of UNC-89 (Obscurin) in Caenorhabditis elegans.
AB  - Mutation of the Caenorhabditis elegans gene unc-89 results in disorganization of
      muscle A-bands. unc-89 encodes a giant polypeptide (900 kDa) containing two
      protein kinase domains, PK1 and PK2. Yeast two-hybrid screening using a portion
      of UNC-89 including PK2, yielded SCPL-1 (small CTD phosphatase-like-1), which
      contains a C terminal domain (CTD) phosphatase type domain. In addition to the
      PK2 domain, interaction with SCPL-1 required the putative autoinhibitory
      sequence, and immunoglobulin (Ig) and fibronectin type 3 (Fn3) domains lying N
      terminal of the kinase domain. SCPL-1 also interacts with PK1, and it similarly
      requires the kinase domain and upstream Fn3 and Ig domains. Analogous regions
      from the two other giant kinases of C. elegans, twitchin and TTN-1, failed to
      interact with SCPL-1. The interaction between SCPL-1 and either Ig-Fn3-PK2 or Fn3
      Ig-PK1 was confirmed by biochemical methods. The scpl-1b promoter is expressed in
      the same set of muscles as unc-89. Antibodies to SCPL-1 localize to the M-line
      and a portion of the I-band. Bacterially expressed SCPL-1 proteins have
      phosphatase activity in vitro with properties similar to previously characterized
      members of the CTD phosphatase family. RNA interference knockdown results in a
      defect in the function of egg-laying muscles. These studies suggest a new role
      for the CTD phosphatase family, that is, in muscle giant kinase signaling.

PMID- 18337466
TI  - Apical accumulation of Rho in the neural plate is important for neural plate cell
      shape change and neural tube formation.
AB  - Although Rho-GTPases are well-known regulators of cytoskeletal reorganization,
      their in vivo distribution and physiological functions have remained elusive. In
      this study, we found marked apical accumulation of Rho in developing chick
      embryos undergoing folding of the neural plate during neural tube formation, with
      similar accumulation of activated myosin II. The timing of accumulation and
      biochemical activation of both Rho and myosin II was coincident with the dynamics
      of neural tube formation. Inhibition of Rho disrupted its apical accumulation and
      led to defects in neural tube formation, with abnormal morphology of the neural
      plate. Continuous activation of Rho also altered neural tube formation. These
      results indicate that correct spatiotemporal regulation of Rho is essential for
      neural tube morphogenesis. Furthermore, we found that a key morphogenetic
      signaling pathway, the Wnt/PCP pathway, was implicated in the apical accumulation
      of Rho and regulation of cell shape in the neural plate, suggesting that this
      signal may be the spatiotemporal regulator of Rho in neural tube formation.

PMID- 18337467
TI  - Soft substrate up-regulates the interaction of STIM1 with store-operated Ca2+
      channels that lead to normal epithelial cell apoptosis.
AB  - We have demonstrated that soft substrate induced apoptosis in polarized cells,
      but not in transformed cells by disturbance of Ca(2+) homeostasis. This study
      aims to further investigate the regulatory mechanisms underlying the disruption
      of Ca(2+)-signaling integrity in soft substrate-induced epithelial apoptosis.
      Soft substrate up-regulated the store-operated Ca(2+) (SOC) entry across the
      plasma membrane of normal cervical epithelial cells, which resulted in increased
      cytosolic Ca(2+) levels. Concomitantly, soft substrate induced the aggregation
      and translocation of stromal interacting molecule 1 (STIM1) toward the cell
      periphery to colocalize with Orai1, an essential pore subunit of SOC channel,
      detected by fluorescence resonance energy transfer approach and confocal image
      analyses. The disturbed Ca(2+) homeostasis resulted in the activation of mu
      calpain, which cleaved alpha-spectrin, induced actin disorganization, and caused
      apoptosis. In contrast, soft substrate did not disturb Ca(2+) homeostasis or
      induce apoptosis in cervical cancer cells. Chelating extracellular Ca(2+) by EGTA
      and down-regulated SOC entry by small interfering RNA targeting STIM1 or
      inhibitors targeting Ca(2+)-binding site of calpain significantly inhibited soft
      substrate-induced activation of mu-calpain and epithelial cell apoptosis. Thus,
      soft substrate up-regulates the interaction of STIM1 with SOC channels, which
      results in the activation of mu-calpain and subsequently induces normal
      epithelial cell apoptosis.

PMID- 18337468
TI  - Constitutive activation of chaperone-mediated autophagy in cells with impaired
      macroautophagy.
AB  - Three different types of autophagy-macroautophagy, microautophagy, and chaperone
      mediated autophagy (CMA)-contribute to degradation of intracellular components in
      lysosomes in mammalian cells. Although some level of basal macroautophagy and CMA
      activities has been described in different cell types and tissues, these two
      pathways are maximally activated under stress conditions. Activation of these two
      pathways is often sequential, suggesting the existence of some level of cross
      talk between both stress-related autophagic pathways. In this work, we analyze
      the consequences of blockage of macroautophagy on CMA activity. Using mouse
      embryonic fibroblasts deficient in Atg5, an autophagy-related protein required
      for autophagosome formation, we have found that blockage of macroautophagy leads
      to up-regulation of CMA, even under basal conditions. Interestingly, different
      mechanisms contribute to the observed changes in CMA-related proteins and the
      consequent activation of CMA during basal and stress conditions in these
      macroautophagy-deficient cells. This work supports a direct cross-talk between
      these two forms of autophagy, and it identifies changes in the lysosomal
      compartment that underlie the basis for the communication between both autophagic
      pathways.

PMID- 18337469
TI  - Prolyl hydroxylase PHD3 activates oxygen-dependent protein aggregation.
AB  - The HIF prolyl hydroxylases (PHDs/EGLNs) are central regulators of the molecular
      responses to oxygen availability. One isoform, PHD3, is expressed in response to
      hypoxia and causes apoptosis in oxygenated conditions in neural cells. Here we
      show that PHD3 forms subcellular aggregates in an oxygen-dependent manner. The
      aggregation of PHD3 was seen under normoxia and was strongly reduced under
      hypoxia or by the inactivation of the PHD3 hydroxylase activity. The PHD3
      aggregates were dependent on microtubular integrity and contained components of
      the 26S proteasome, chaperones, and ubiquitin, thus demonstrating features that
      are characteristic for aggresome-like structures. Forced expression of the active
      PHD3 induced the aggregation of proteasomal components and activated apoptosis
      under normoxia in HeLa cells. The apoptosis was seen in cells prone to PHD3
      aggregation and the PHD3 aggregation preceded apoptosis. The data demonstrates
      the cellular oxygen sensor PHD3 as a regulator of protein aggregation in response
      to varying oxygen availability.

PMID- 18337470
TI  - Alg13p, the catalytic subunit of the endoplasmic reticulum UDP-GlcNAc
      glycosyltransferase, is a target for proteasomal degradation.
AB  - The second step of dolichol-linked oligosaccharide synthesis in the N-linked
      glycosylation pathway at the endoplasmic reticulum (ER) membrane is catalyzed by
      an unusual hetero-oligomeric UDP-N-acetylglucosamine transferase that in most
      eukaryotes is comprised of at least two subunits, Alg13p and Alg14p. Alg13p is
      the cytosolic and catalytic subunit that is recruited to the ER by the membrane
      protein Alg14p. We show that in Saccharomyces cerevisiae, cytosolic Alg13p is
      very short-lived, whereas membrane-associated Alg13 is relatively stable.
      Cytosolic Alg13p is a target for proteasomal degradation, and the failure to
      degrade excess Alg13p leads to glycosylation defects. Alg13p degradation does not
      require ubiquitin but instead, requires a C-terminal domain whose deletion
      results in Alg13p stability. Conversely, appending this sequence onto normally
      long-lived beta-galactosidase causes it to undergo rapid degradation,
      demonstrating that this C-terminal domain represents a novel and autonomous
      degradation motif. These data lead to the model that proteasomal degradation of
      excess unassembled Alg13p is an important quality control mechanism that ensures
      proper protein complex assembly and correct N-linked glycosylation.

PMID- 18337471
TI  - Functional redundancy of the B9 proteins and nephrocystins in Caenorhabditis
      elegans ciliogenesis.
AB  - Meckel-Gruber syndrome (MKS), nephronophthisis (NPHP), and Joubert syndrome
      (JBTS) are a group of heterogeneous cystic kidney disorders with partially
      overlapping loci. Many of the proteins associated with these diseases interact
      and localize to cilia and/or basal bodies. One of these proteins is MKS1, which
      is disrupted in some MKS patients and contains a B9 motif of unknown function
      that is found in two other mammalian proteins, B9D2 and B9D1. Caenorhabditis
      elegans also has three B9 proteins: XBX-7 (MKS1), TZA-1 (B9D2), and TZA-2 (B9D1).
      Herein, we report that the C. elegans B9 proteins form a complex that localizes
      to the base of cilia. Mutations in the B9 genes do not overtly affect cilia
      formation unless they are in combination with a mutation in nph-1 or nph-4, the
      homologues of human genes (NPHP1 and NPHP4, respectively) that are mutated in
      some NPHP patients. Our data indicate that the B9 proteins function redundantly
      with the nephrocystins to regulate the formation and/or maintenance of cilia and
      dendrites in the amphid and phasmid ciliated sensory neurons. Together, these
      data suggest that the human homologues of the novel B9 genes B9D2 and B9D1 will
      be strong candidate loci for pathologies in human MKS, NPHP, and JBTS.

PMID- 18337472
TI  - Lectin-deficient calreticulin retains full functionality as a chaperone for class
      I histocompatibility molecules.
AB  - Calreticulin is a molecular chaperone of the endoplasmic reticulum that uses both
      a lectin site specific for Glc(1)Man(5-9)GlcNAc(2) oligosaccharides and a
      polypeptide binding site to interact with nascent glycoproteins. The latter mode
      of substrate recognition is controversial. To examine the relevance of
      polypeptide binding to protein folding in living cells, we prepared lectin
      deficient mutants of calreticulin and examined their abilities to support the
      assembly and quality control of mouse class I histocompatibility molecules. In
      cells lacking calreticulin, class I molecules exhibit inefficient loading of
      peptide ligands, reduced cell surface expression and aberrantly rapid export from
      the endoplasmic reticulum. Remarkably, expression of calreticulin mutants that
      are completely devoid of lectin function fully complemented all of the class I
      biosynthetic defects. We conclude that calreticulin can use nonlectin-based modes
      of substrate interaction to effect its chaperone and quality control functions on
      class I molecules in living cells. Furthermore, pulse-chase coimmunoisolation
      experiments revealed that lectin-deficient calreticulin bound to a similar
      spectrum of client proteins as wild-type calreticulin and dissociated with
      similar kinetics, suggesting that lectin-independent interactions are commonplace
      in cells and that they seem to be regulated during client protein maturation.

PMID- 18337473
TI  - Partial deletion of the nicotinic cholinergic receptor alpha 4 or beta 2 subunit
      genes changes the acetylcholine sensitivity of receptor-mediated 86Rb+ efflux in
      cortex and thalamus and alters relative expression of alpha 4 and beta 2
      subunits.
AB  - Alpha4 and beta2 nicotinic cholinergic receptor (nAChR) subunits can assemble in
      heterologous expression systems as pentameric receptors with different subunit
      stoichiometries that exhibit differential sensitivity to activation by
      acetylcholine, yielding biphasic concentration-effect curves. nAChR-mediated
      (86)Rb(+) efflux in mouse brain synaptosomes also displays biphasic acetylcholine
      (ACh) concentration-response curves. Both phases are mediated primarily by
      alpha4beta2(*)-nAChR, because deletion of either the alpha4 or beta2 subunit
      reduces response at least 90%. A relatively larger decrease in the component of
      (86)Rb(+) efflux with lower ACh sensitivity occurred with partial deletion of
      alpha4 (alpha4(+/-)), whereas a larger decrease in the component with higher ACh
      sensitivity was elicited by partial deletion of beta2 (beta2(+/-)).
      Immunoprecipitation with selective antibodies demonstrated that more than 70% of
      [(3)H]epibatidine binding sites in both regions contained only alpha4 and beta2
      subunits. Subsequently, alpha4 and beta2 subunit content in the cortex and
      thalamus of alpha4 and beta2 wild types and heterozygotes was analyzed with
      Western blots. Partial deletion of alpha4 decreased and partial deletion of beta2
      increased the relative proportion of the alpha4 subunit in assembled receptors.
      Although these methods do not allow exact identification of stoichiometry of the
      subtypes present in wild-type cortex and thalamus, they do demonstrate that
      cortical and thalamic nAChRs of the alpha4(+/-) and beta2(+/-) genotypes differ
      in relative expression of alpha4 and beta2 subunits a result that corresponds to
      the relative functional changes observed after partial gene deletion. These
      results strongly suggest that alpha4beta2-nAChR with different stoichiometry are
      expressed in native tissue.

PMID- 18337474
TI  - Interleukin-13 neutralization by two distinct receptor blocking mechanisms
      reduces immunoglobulin E responses and lung inflammation in cynomolgus monkeys.
AB  - Interleukin (IL)-13 is a key cytokine driving allergic and asthmatic responses
      and contributes to airway inflammation in cynomolgus monkeys after segmental
      challenge with Ascaris suum antigen. IL-13 bioactivity is mediated by a
      heterodimeric receptor (IL-13Ralpha1/IL-4Ralpha) and can be inhibited in vitro by
      targeting IL-13 interaction with either chain. However, in cytokine systems, in
      vitro neutralization activity may not always predict inhibitory function in vivo.
      To address the efficacy of two different IL-13 neutralization mechanisms in a
      primate model of atopic disease, two humanized monoclonal antibodies to IL-13
      were generated, with highly homologous properties, differing in epitope
      recognition. Ab01 blocks IL-13 interaction with IL-4Ralpha, and Ab02 blocks IL-13
      interaction with IL-13Ralpha1. In a cynomolgus monkey model of IgE responses to
      A. suum antigen, both Ab01 and Ab02 effectively reduced serum titers of Ascaris
      specific IgE and diminished ex vivo Ascaris-triggered basophil histamine release,
      assayed 8 weeks after a single administration of antibody. The two antibodies
      also produced comparable reductions in pulmonary inflammation after lung
      segmental challenge with Ascaris antigen. Increased serum levels of IL-13,
      lacking demonstrable biological activity, were seen postchallenge in animals
      given either anti-IL-13 antibody but not in control animals given human IgG of
      irrelevant specificity. These findings demonstrate a potent effect of IL-13
      neutralization on IgE-mediated atopic responses in a primate system and show that
      IL-13 can be efficiently neutralized by targeting either the IL-4Ralpha-binding
      epitope or the IL-13Ralpha1-binding epitope.

PMID- 18337475
TI  - Protoapigenone, a novel flavonoid, induces apoptosis in human prostate cancer
      cells through activation of p38 mitogen-activated protein kinase and c-Jun NH2
      terminal kinase 1/2.
AB  - In this study, we investigated the anticancer effect of protoapigenone on human
      prostate cancer cells. Protoapigenone inhibited cell growth through arresting
      cancer cells at S and G(2)/M phases as well as inducing apoptosis. Blockade of
      cell cycle by protoapigenone was associated with an increase in the levels of
      inactivated phospho (p)-Cdc25C (Ser216) and a decrease in the levels of activated
      p-cyclin B1 (Ser147), cyclin B1, and cyclin-dependent kinase (Cdk) 2.
      Protoapigenone triggered apoptosis by increasing the levels of cleaved poly(ADP
      ribose) polymerase and caspase-3. In addition, activation of p38 mitogen
      activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK)1/2 was a
      critical mediator in protoapigenone-induced cell death. Inhibition of the
      expression of p38 MAPK and JNK1/2 by pharmacological inhibitors or specific small
      interfering RNA reversed the protoapigenone-induced apoptosis through decreasing
      the level of cleaved caspase-3. In contrast, p38 MAPK, but not JNK1/2, was
      involved in the protoapigenone-mediated S and G(2)/M arrest by modulating the
      levels of Cdk2 and p-Cdc25C (Ser216). Moreover, in vivo xenograft study showed
      that protoapigenone had a significant inhibition of prostate tumor growth without
      major side effects on the mice we tested. This inhibition was associated with
      induction of apoptosis and activation of p38 MAPK and JNK1/2 in protoapigenone
      treated tumor tissues. In conclusion, our results demonstrated protoapigenone
      suppressed prostate cancer cell growth through the activation of p38 MAPK and
      JNK1/2, with the potential to be developed as a chemotherapeutic agent for
      prostate cancer.

PMID- 18337476
TI  - Synthesis and pharmacological in vitro and in vivo profile of 3-oxo-1,1-diphenyl
      tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA
      68), a selective antagonist of the neuropeptide S receptor.
AB  - Neuropeptide S (NPS) has been shown to modulate arousal, sleep wakefulness,
      anxiety-like behavior, and feeding after central administration of the peptide
      agonist to mice or rats. We report here the chemical synthesis and
      pharmacological characterization of SHA 66 (3-oxo-1,1-diphenyl-tetrahydro
      oxazolo[3,4-a]pyrazine-7-carboxylic acid benzylamide) and SHA 68 (3-oxo-1,1
      diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro
      benzylamide), two closely related bicyclic piperazines with antagonistic
      properties at the NPS receptor (NPSR). The compounds block NPS-induced Ca2+
      mobilization, and SHA 68 shows displaceable binding to NPSR in the nanomolar
      range. The antagonistic activity of SHA 68 seems to be specific because it does
      not affect signaling at 14 unrelated G protein-coupled receptors. Analysis of
      pharmacokinetic parameters of SHA 68 demonstrates that the compound reaches
      pharmacologically relevant levels in plasma and brain after i.p. administration.
      Furthermore, peripheral administration of SHA 68 in mice (50 mg/kg i.p.) is able
      to antagonize NPS-induced horizontal and vertical activity as well as stereotypic
      behavior. Therefore, SHA 68 could be a useful tool to characterize physiological
      functions and pharmacological parameters of the NPS system in vitro and in vivo.

PMID- 18337477
TI  - Muscarinic M4 receptor recycling requires a motif in the third intracellular
      loop.
AB  - The present study was performed to identify sequence(s) in the third
      intracellular loop (i3) of the muscarinic acetylcholine receptor M4 subtype (M4
      receptor) involved in its internalization and recycling. In transiently
      transfected human embryonic kidney 293-tsA201 cells, 40 to 50% of cell-surface M4
      receptors are internalized in an agonist-dependent manner, and approximately 65%
      of internalized receptors are recycled back to the cell surface after removal of
      the agonist. We examined the internalization and recycling of M4 receptor mutants
      with partial deletion in i3 and found that various mutants (M4del-K(235)-K(240),
      M4del-T(241)-K(271), and M4del-W(339)-N(372)) showed internalization and cell
      surface recycling in a similar manner to the M4 receptor. We also found that the
      mutant M4del-L(272)-R(338) was internalized to only half the extent of the M4
      receptor and was recycled after agonist removal, and the mutant M4del-V(373)
      A(393) was also internalized to half the extent of the wild type but was not
      recycled back to the cell surface after agonist removal. When the sequence
      corresponding to Val(373)-Ala(393) was grafted onto the i3 portion of a recycling
      negative mutant of muscarinic M2 receptor with deletion of almost the whole of
      the i3 sequence, approximately 40% of the chimeric receptor on the cell surface
      was internalized, and more than 65% of the internalized receptors were recycled
      back to the cell surface. These results indicate that the regions including
      Leu(272)-Arg(338) and Val(373)-Ala(393) are involved in internalization of the M4
      receptor, and the region including Val(373)-Ala(393) is indispensable for its
      recycling, whereas the other regions of i3 are dispensable for internalization
      and recycling.

PMID- 18337478
TI  - When is it appropriate to use vasopressin receptor antagonists?
AB  - Hyponatremia is a common and challenging disorder. The mainstays of treatment
      until recently were water restriction and hypertonic saline. The first nonpeptide
      vasopressin receptor antagonist (VRA) is now approved by the US Food and Drug
      Administration for use in patients with euvolemic and hypervolemic hyponatremia.
      VRA induce urinary dilution with an aquaresis that leads to an increase in serum
      sodium concentration. In patients with heart failure, VRA modestly improve
      congestive symptoms but have no effect on short- or long-term mortality. Long
      term effects have not been extensively studied, but serious adverse effects of
      VRA are rare, and the rate of rise in serum sodium that they produce seems
      unlikely to lead to osmotic demyelination. Beneficial effects beyond changing
      serum tonicity and alternative uses, such as in polycystic kidney disease, need
      further exploration. This commentary discusses the current and potential
      indications for use of VRA.

PMID- 18337479
TI  - CXCL9, but not CXCL10, promotes CXCR3-dependent immune-mediated kidney disease.
AB  - Chemokines are instrumental in macrophage- and T cell-dependent diseases. The
      chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis
      (MRL-Fas(lpr) mice and the nephrotoxic serum nephritis model), but evidence
      suggests that multiple chemokines are involved. For identification of additional
      therapeutic targets for immune-mediated nephritis, chemokine ligands and
      receptors in CCL2-/- and wild-type (WT) MRL-Fas(lpr) kidneys were profiled. The
      focus was on intrarenal chemokine ligand/receptor pairs that were highly
      upregulated downstream of CCL2; the chemokine CXCL10 and its cognate receptor,
      CXCR3, stood out as potential therapeutic targets. However, renal disease was not
      suppressed in CXCL10-/- MRL-Fas(lpr) mice, and CXCL10-/- C57BL/6 mice were not
      protected from nephrotoxic serum nephritis compared with WT mice. Because CXCR3
      engages with the ligand CXCL9, CXCR3-/- , CXCL9-/- , and CXCL10-/- B6 mice were
      compared with WT mice with nephrotoxic serum nephritis. Kidney disease, measured
      by loss of renal function and histopathology, was suppressed in both CXCR3-/- and
      CXCL9-/- mice but not in CXCL10-/- mice. With nephrotoxic serum nephritis, CXCR3
      /- and CXCL9-/- mice had fewer intrarenal activated T cells and activated
      macrophages. Both IgG glomerular deposits and antigen-specific IgG in serum were
      reduced in these mice, suggesting that although CXCR3 and CXCL9 initiate
      nephritis through cell-mediated events, renal inflammation may be sustained by
      their regulation of IgG. It is concluded that specific blockade of CXCL9

PMID- 18337480
TI  - Standard versus high-dose CVVHDF for ICU-related acute renal failure.
AB  - The effect of dosage of continuous venovenous hemodiafiltration (CVVHDF) on
      survival in patients with acute renal failure (ARF) is unknown. In this study,
      200 critically ill patients with ARF were randomly assigned to receive CVVHDF
      with prefilter replacement fluid at an effluent rate of either 35 ml/kg per h
      (high dosage) or 20 ml/kg per h (standard dosage). The primary study outcome,
      survival to the earlier of either intensive care unit discharge or 30 d, was 49%
      in the high-dosage arm and 56% in the standard-dosage arm (odds ratio 0.75; 95%
      confidence interval 0.43 to 1.32; P = 0.32). Among hospital survivors, 69% of
      those in the high-dosage arm recovered renal function compared with 80% of those
      in the standard-dosage arm (P = 0.29); therefore, a difference in patient
      survival or renal recovery was not detected between patients receiving high
      dosage or standard-dosage CVVHDF.

PMID- 18337481
TI  - Uric acid and incident kidney disease in the community.
AB  - Uric acid may mediate aspects of the relationship between hypertension and kidney
      disease via renal vasoconstriction and systemic hypertension. To investigate the
      relationship between uric acid and subsequent reduced kidney function, limited
      access data of 13,338 participants with intact kidney function in two community
      based cohorts, the Atherosclerosis Risks in Communities and the Cardiovascular
      Health Study, were pooled. Mean baseline serum uric acid was 5.9 +/- 1.5 mg/dl,
      mean baseline serum creatinine was 0.9 +/- 0.2 mg/dl, and mean baseline estimated
      GFR was 90.4 +/- 19.4 ml/min/1.73 m(2). During 8.5 +/- 0.9 yr of follow-up, 712
      (5.6%) had incident kidney disease defined by GFR decrease (>or=15 ml/min/1.73
      m(2) with final GFR <60 ml/min/1.73 m(2)), while 302 (2.3%) individuals had
      incident kidney disease defined by creatinine increase (>or=0.4 mg/dl with final
      serum creatinine >1.4 mg/dl in men and 1.2 mg/dl in women). In GFR- and
      creatinine-based logistic regression models, baseline uric acid level was
      associated with increased risk for incident kidney disease (odds ratio 1.07 [95%
      confidence interval 1.01 to 1.14] and 1.11 [95% confidence interval 1.02 to 1.21]
      per 1-mg/dl increase in uric acid, respectively), after adjustment for age,
      gender, race, diabetes, systolic BP, hypertension, cardiovascular disease, left
      ventricular hypertrophy, smoking, alcohol use, education, lipids, albumin,
      hematocrit, baseline kidney function and cohort; therefore, elevated serum uric
      acid level is a modest, independent risk factor for incident kidney disease in
      the general population.

PMID- 18337482
TI  - Impact of solute intake on urine flow and water excretion.
AB  - It is classically taught that when renal function is normal and the secretion of
      antidiuretic hormone (arginine vasopressin) is fully suppressed, the human kidney
      has the capacity to excrete large volumes of dilute urine, allowing for a broad
      range of water intake. This flexibility protects against the development of
      hyponatremia even in the face of water intake that can approach 20 L/d. What is
      not as widely recognized is the impact that alterations in solute intake, and
      therefore excretion, have on this process. As will be illustrated here, a
      decrement in solute intake markedly reduces the above-mentioned flexibility and
      puts the individual at risk for the unexpected development of hyponatremia. In
      contrast, an increment in solute intake can be used therapeutically to treat this
      electrolyte disorder and allow those prone to it to liberalize their water
      intake.

PMID- 18337483
TI  - Long-term efficacy and safety of a calcineurin inhibitor-free regimen in live
      donor renal transplant recipients.
AB  - Calcineurin inhibitor (CNI) nephrotoxicity is a major concern after renal
      transplantation. To investigate the safety and efficacy of a CNI-free
      immunosuppressive regimen, 132 live-donor renal transplant recipients were
      included in a prospective, randomized controlled trial. All patients received
      induction therapy with basiliximab and steroids. The patients were randomized to
      a maintenance immunosuppression regimen that included steroids, sirolimus, and
      either low-dose tacrolimus or mycophenolate mofetil (MMF). Over a mean follow-up
      period of approximately 5 yr, patient and graft survival did not significantly
      differ between the two maintenance regimens. Patient survival was 93.8% and 98.5%
      in the tacrolimus/sirolimus and MMF/sirolimus groups, respectively, and graft
      survival was 83% and 88%, respectively. However, the MMF/sirolimus group had
      significantly better renal function, calculated by Cockcroft-Gault, from the
      second year post-transplant until the last follow-up. In addition, this group was
      less likely to require a change in their primary immunosuppression regimen than
      the tacrolimus/sirolimus group (20.8% versus 53.8%, P = 0.001). The safety
      profile was similar between groups. In summary, after long-term follow-up, a CNI
      free maintenance regimen consisting of sirolimus, MMF, and steroids was both safe
      and efficacious among low to moderate immunologic risk renal transplant
      recipients.

PMID- 18337484
TI  - A bimodal association of vitamin D levels and vascular disease in children on
      dialysis.
AB  - In addition to its classical role in calcium-phosphate homeostasis, vitamin D has
      anti-inflammatory effects that may influence vascular disease. This study
      examined the impact of vitamin D levels on the vascular phenotype in 61 children
      who had been on dialysis for >or=3 mo and in 40 age-matched control subjects. All
      dialysis patients were prescribed daily oral 1-alpha hydroxyvitamin D(3). 92% of
      patients were deficient in 25-hydroxyvitamin D [25(OH)D]. 1,25-dihydroxyvitamin D
      [1,25(OH)(2)D] levels were low in 36% and high in 11% of patients. There was a
      weak correlation between 1 alpha-hydroxyvitamin D(3) dosage and 1,25(OH)(2)D
      levels. Both carotid intima-media thickness and calcification scores showed a U
      shaped distribution across 1,25(OH)(2)D levels: patients with both low and high
      1,25(OH)(2)D had significantly greater carotid intima-media thickness (P <
      0.0001) and calcification (P = 0.0002) than those with normal levels. Low
      1,25(OH)(2)D levels were associated with higher high-sensitivity C-reactive
      protein (P < 0.0001). Calcification was most frequently observed in patients with
      the lowest 1,25(OH)(2)D and the highest high-sensitivity C-reactive protein. In
      contrast, 25(OH)D levels did not correlate with any vascular measure. In
      conclusion, both low and high 1,25(OH)(2)D levels are associated with adverse
      morphologic changes in large arteries, and this may be mediated through the
      effects of 1,25(OH)(2)D on calcium-phosphate homeostasis and inflammation. For
      optimization of strategies to protect the vasculature of dialysis patients,
      careful monitoring of 1,25(OH)(2)D levels may be required.

PMID- 18337485
TI  - IL-6/IL-6R axis plays a critical role in acute kidney injury.
AB  - The response to tissue injury involves the coordination of inflammatory and
      repair processes. IL-6 expression correlates with the onset and severity of acute
      kidney injury (AKI), but its contribution to pathogenesis remains unclear. This
      study established a critical role for IL-6 in both the inflammatory response and
      the resolution of AKI. IL-6-deficient mice were resistant to HgCl2-induced AKI
      compared with wild-type mice. The accumulation of peritubular neutrophils was
      lower in IL-6-deficient mice than in wild-type mice, and neutrophil depletion
      before HgCl2 administration in wild-type mice significantly reduced AKI; these
      results demonstrate the critical role of IL-6 signaling in the injurious
      inflammatory process in AKI. Renal IL-6 expression and STAT3 activation in renal
      tubular epithelial cells significantly increased during the development of
      injury, suggesting active IL-6 signaling. Although a lack of renal IL-6 receptors
      (IL-6R) precludes the activation of classical signaling pathways, IL-6 can
      stimulate target cells together with a soluble form of the IL-6R (sIL-6R) in a
      process termed trans-signaling. During injury,serum sIL-6R levels increased three
      fold, suggesting a possible role for IL-6 trans-signaling in AKI. Stimulation of
      IL-6 trans-signaling with an IL-6/sIL-6R fusion protein activated STAT3 in renal
      tubular epithelium and prevented AKI. IL-6/sIL-6R reduced lipid peroxidation
      after injury, suggesting that its protective effect may be largely mediated
      through amelioration of oxidative stress. In summary, IL-6 simultaneously
      promotes an injurious inflammatory response and, through a mechanism of trans
      signaling, protects the kidney from further injury.

PMID- 18337486
TI  - Role of integrins in the assembly and function of hensin in intercalated cells.
AB  - Epithelial differentiation proceeds in at least two steps: Conversion of a
      nonepithelial cell into an epithelial sheet followed by terminal differentiation
      into the mature epithelial phenotype. It was recently discovered that the
      extracellular matrix (ECM) protein hensin is able to convert a renal intercalated
      cell line from a flat, squamous shape into a cuboidal or columnar epithelium.
      Global knockout of hensin in mice results in embryonic lethality at the time that
      the first columnar cells appear. Here, antibodies that either activate or block
      integrin beta1 were used to demonstrate that activation of integrin alpha v beta
      1 causes deposition of hensin in the ECM. Once hensin polymerizes and deposits
      into the ECM, it binds to integrin alpha 6 and mediates the conversion of
      epithelial cells to a cuboidal phenotype capable of apical endocytosis;
      therefore, multiple integrins play a role in the terminal differentiation of the
      intercalated cell: alpha v beta 1 generates polymerized hensin, and another set
      of integrins (containing alpha 6) mediates signals between hensin and the
      interior of the cells.

PMID- 18337487
TI  - Renin-angiotensin system blockade is renoprotective in immune complex-mediated
      glomerulonephritis.
AB  - Blockade of the renin-angiotensin system is renoprotective in a variety of
      chronic nephropathies, but the direct effect of such treatment in active, immune
      complex-mediated glomerulonephritis is unknown. This study investigated the short
      and long-term effects of an angiotensin-converting enzyme inhibitor (enalapril)
      and an angiotensin II type 1 receptor blocker (losartan) in thymic stromal
      lymphopoietin transgenic (TSLPtg) mice, which develop mixed cryoglobulinemia and
      severe cryoglobulinemia-associated membranoproliferative glomerulonephritis.
      Enalapril and losartan each reduced hypertension, proteinuria, glomerular
      extracellular matrix deposition, and mesangial cell activation in TSLPtg mice.
      These renoprotective effects were not observed with hydralazine treatment,
      despite a similar antihypertensive effect. Treatment with enalapril or losartan
      also decreased renal plasminogen activator inhibitor-1 in TSLPtg mice, assessed
      by immunohistochemistry and quantitative real-time reverse transcriptase-PCR.
      None of the treatments affected immune complex deposition or macrophage
      infiltration. Overall, enalapril- and losartan-treated TSLPtg mice survived
      significantly longer than untreated TSLPtg mice. These studies demonstrate that
      angiotensin blockade may provide renoprotective benefits, independent of its BP
      lowering effect, in the treatment of active immune complex-mediated
      glomerulonephritis.

PMID- 18337488
TI  - Ectopic notch activation in developing podocytes causes glomerulosclerosis.
AB  - Genetic evidence supports an early role for Notch signaling in the fate of
      podocytes during glomerular development. Decreased expression of Notch
      transcriptional targets in developing podocytes after the determination of cell
      fate suggests that constitutive Notch signaling may oppose podocyte
      differentiation. This study determined the effects of constitutive Notch
      signaling on podocyte differentiation by ectopically expressing Notch's
      intracellular domain (NOTCH-IC), the biologically active, intracellular product
      of proteolytic cleavage of the Notch receptor, in developing podocytes of
      transgenic mice. Histologic and molecular analyses revealed normal glomerular
      morphology and expression of podocyte markers in newborn NOTCH-IC-expressing
      mice; however, mice developed severe proteinuria and showed evidence of
      progressive glomerulosclerosis at 2 wk after birth. Features of mature podocytes
      were lost: Foot processes were effaced; expression of Wt1, Nphs1, and Nphs2 was
      downregulated; cell-cycle re-entry was induced; and the expression of Pax2 was
      increased. In contrast, mice with podocyte-specific inactivation of Rbpsuh, which
      encodes a protein essential for canonical Notch signaling, seemed normal. In
      addition, the damaging effects of NOTCH-IC expression were prevented in
      transgenic mice after simultaneous conditional inactivation of Rbpsuh in murine
      podocytes. These results suggest that Notch signaling is dispensable during
      terminal differentiation of podocytes but that constitutive (or inappropriate)
      Notch signaling is deleterious, leading to glomerulosclerosis.

PMID- 18337489
TI  - Tobacco transcription factors: novel insights into transcriptional regulation in
      the Solanaceae.
AB  - Tobacco (Nicotiana tabacum) is a member of the Solanaceae, one of the
      agronomically most important groups of flowering plants. We have performed an in
      silico analysis of 1.15 million gene-space sequence reads from the tobacco
      nuclear genome and report the detailed analysis of more than 2,500 tobacco
      transcription factors (TFs). The tobacco genome contains at least one member of
      each of the 64 well-characterized TF families identified in sequenced vascular
      plant genomes, indicating that evolution of the Solanaceae was not associated
      with the gain or loss of TF families. However, we found notable differences
      between tobacco and non-Solanaceae species in TF family size and evidence for
      both tobacco- and Solanaceae-specific subfamily expansions. Compared with TF
      families from sequenced plant genomes, tobacco has a higher proportion of
      ERF/AP2, C2H2 zinc finger, homeodomain, GRF, TCP, zinc finger homeodomain, BES,
      and STERILE APETALA (SAP) genes and novel subfamilies of BES, C2H2 zinc finger,
      SAP, and NAC genes. The novel NAC subfamily, termed TNACS, appears restricted to
      the Solanaceae, as they are absent from currently sequenced plant genomes but
      present in tomato (Solanum lycopersicum), pepper (Capsicum annuum), and potato
      (Solanum tuberosum). They constitute approximately 25% of NAC genes in tobacco.
      Based on our phylogenetic studies, we predict that many of the more than 50
      tobacco group IX ERF genes are involved in jasmonate responses. Consistent with
      this, over two-thirds of group IX ERF genes tested showed increased mRNA levels
      following jasmonate treatment. Our data are a major resource for the Solanaceae
      and fill a void in studies of TF families across the plant kingdom.

PMID- 18337490
TI  - Decrease in manganese superoxide dismutase leads to reduced root growth and
      affects tricarboxylic acid cycle flux and mitochondrial redox homeostasis.
AB  - Superoxide dismutases (SODs) are key components of the plant antioxidant defense
      system. While plastidic and cytosolic isoforms have been extensively studied, the
      importance of mitochondrial SOD at a cellular and whole-plant level has not been
      established. To address this, transgenic Arabidopsis (Arabidopsis thaliana)
      plants were generated in which expression of AtMSD1, encoding the mitochondrial
      manganese (Mn)SOD, was suppressed by antisense. The strongest antisense line
      showed retarded root growth even under control growth conditions. There was
      evidence for a specific disturbance of mitochondrial redox homeostasis in
      seedlings grown in liquid culture: a mitochondrially targeted redox-sensitive
      green fluorescent protein was significantly more oxidized in the MnSOD-antisense
      background. In contrast, there was no substantial change in oxidation of
      cytosolically targeted redox-sensitive green fluorescent protein, nor changes in
      antioxidant defense components. The consequences of altered mitochondrial redox
      status of seedlings were subtle with no widespread increase of mitochondrial
      protein carbonyls or inhibition of mitochondrial respiratory complexes. However,
      there were specific inhibitions of tricarboxylic acid (TCA) cycle enzymes
      (aconitase and isocitrate dehydrogenase) and an inhibition of TCA cycle flux in
      isolated mitochondria. Nevertheless, total respiratory CO2 output of seedlings
      was not decreased, suggesting that the inhibited TCA cycle enzymes can be
      bypassed. In older, soil-grown plants, redox perturbation was more pronounced
      with changes in the amount and/or redox poise of ascorbate and glutathione.
      Overall, the results demonstrate that reduced MnSOD affects mitochondrial redox
      balance and plant growth. The data also highlight the flexibility of plant
      metabolism with TCA cycle inhibition having little effect on overall respiratory
      rates.

PMID- 18337491
TI  - Rapid chemotactic response enables marine bacteria to exploit ephemeral
      microscale nutrient patches.
AB  - Because ocean water is typically resource-poor, bacteria may gain significant
      growth advantages if they can exploit the ephemeral nutrient patches originating
      from numerous, small sources. Although this interaction has been proposed to
      enhance biogeochemical transformation rates in the ocean, it remains questionable
      whether bacteria are able to efficiently use patches before physical mechanisms
      dissipate them. Here we show that the rapid chemotactic response of the marine
      bacterium Pseudoalteromonas haloplanktis substantially enhances its ability to
      exploit nutrient patches before they dissipate. We investigated two types of
      patches important in the ocean: nutrient pulses and nutrient plumes, generated
      for example from lysed algae and sinking organic particles, respectively. We used
      microfluidic devices to create patches with environmentally realistic dimensions
      and dynamics. The accumulation of P. haloplanktis in response to a nutrient pulse
      led to formation of bacterial hot spots within tens of seconds, resulting in a 10
      fold higher nutrient exposure for the fastest 20% of the population compared with
      nonmotile cells. Moreover, the chemotactic response of P. haloplanktis was >10
      times faster than the classic chemotaxis model Escherichia coli, leading to twice
      the nutrient exposure. We demonstrate that such rapid response allows P.
      haloplanktis to colonize nutrient plumes for realistic particle sinking speeds,
      with up to a 4-fold nutrient exposure compared with nonmotile cells. These
      results suggest that chemotactic swimming strategies of marine bacteria in patchy
      nutrient seascapes exert strong influence on carbon turnover rates by triggering
      the formation of microscale hot spots of bacterial productivity.

PMID- 18337492
TI  - Factors promoting marine invasions: a chemoecological approach.
AB  - The Mediterranean Sea is losing its biological distinctiveness, and the same
      phenomenon is occurring in other seas. It gives urgency to a better understanding
      of the factors that affect marine biological invasions. A chemoecological
      approach is proposed here to define biotic conditions that promote biological
      invasions in terms of enemy escape and resource opportunities. Research has
      focused on the secondary metabolite composition of three exotic sea slugs found
      in Greece that have most probably entered the Mediterranean basin by Lessepsian
      migration, an exchange that contributes significantly to Mediterranean
      biodiversity. We have found toxic compounds with significant activity as feeding
      deterrents both in the cephalaspidean Haminoea cyanomarginata and in the
      nudibranch Melibe viridis. These findings led us to propose aposematism in the
      former and dietary autonomy in producing defensive metabolites in the latter
      case, as predisposing factors to the migration. In the third mollusk
      investigated, the anaspidean Syphonota geographica, the topic of marine invasions
      has been approached through a study of its feeding biology. The identification of
      the same compounds from both the viscera of each individual, separately analyzed,
      and their food, the seagrass Halophila stipulacea, implies a dietary dependency.
      The survival of S. geographica in the Mediterranean seems to be related to the
      presence of H. stipulacea. The initial invasion of this exotic pest would seem to
      have paved the way for the subsequent invasion of a trophic specialist that takes
      advantage of niche opportunities.

PMID- 18337493
TI  - CAPON modulates cardiac repolarization via neuronal nitric oxide synthase
      signaling in the heart.
AB  - Congenital long- or short-QT syndrome may lead to life-threatening ventricular
      tachycardia and sudden cardiac death. Apart from the rare disease-causing
      mutations, common genetic variants in CAPON, a neuronal nitric oxide synthase
      (NOS1) regulator, have recently been associated with QT interval variations in a
      human whole-genome association study. CAPON had been unsuspected of playing a
      role in cardiac repolarization; indeed, its physiological role in the heart (if
      any) is unknown. To define the biological effects of CAPON in the heart, we
      investigated endogenous CAPON protein expression and protein-protein interactions
      in the heart and performed electrophysiological studies in isolated ventricular
      myocytes with and without CAPON overexpression. We find that CAPON protein is
      expressed in the heart and interacts with NOS1 to accelerate cardiac
      repolarization by inhibition of L-type calcium channel. Our findings provide a
      rationale for the association of CAPON gene variants with extremes of the QT
      interval in human populations.

PMID- 18337494
TI  - Temporal compression mediated by short-term synaptic plasticity.
AB  - Time scales of cortical neuronal dynamics range from few milliseconds to hundreds
      of milliseconds. In contrast, behavior occurs on the time scale of seconds or
      longer. How can behavioral time then be neuronally represented in cortical
      networks? Here, using electrophysiology and modeling, we offer a hypothesis on
      how to bridge the gap between behavioral and cellular time scales. The core idea
      is to use a long time constant of decay of synaptic facilitation to translate
      slow behaviorally induced temporal correlations into a distribution of synaptic
      response amplitudes. These amplitudes can then be transferred to a sequence of
      action potentials in a population of neurons. These sequences provide temporal
      correlations on a millisecond time scale that are able to induce persistent
      synaptic changes. As a proof of concept, we provide simulations of a neuron that
      learns to discriminate temporal patterns on a time scale of seconds by synaptic
      learning rules with a millisecond memory buffer. We find that the conversion from
      synaptic amplitudes to millisecond correlations can be strongly facilitated by
      subthreshold oscillations both in terms of information transmission and success
      of learning.

PMID- 18337495
TI  - PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated
      atherosclerosis.
AB  - Activation of the nuclear hormone receptor peroxisome proliferator-activated
      receptor delta (PPARdelta) has been shown to improve insulin resistance,
      adiposity, and plasma HDL levels. However, its antiatherogenic role remains
      controversial. Here we report atheroprotective effects of PPARdelta activation in
      a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by
      increased vascular inflammation related to repression of an antiinflammatory
      corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled
      signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the
      PPARdelta agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII
      accelerated atherosclerosis without altering blood pressure and increased
      vascular expression of Bcl-6, RGS4, and RGS5, which was associated with
      suppression of inflammatory and atherogenic gene expression in the artery. In
      vitro studies demonstrated similar changes in AngII-treated macrophages:
      PPARdelta activation increased both total and free Bcl-6 levels and inhibited
      AngII activation of MAP kinases, p38, and ERK1/2. These studies uncover crucial
      proinflammatory mechanisms of AngII and highlight actions of PPARdelta activation
      to inhibit AngII signaling, which is atheroprotective.

PMID- 18337496
TI  - A simple and exact Laplacian clustering of complex networking phenomena:
      application to gene expression profiles.
AB  - Unraveling of the unified networking characteristics of complex networking
      phenomena is of great interest yet a formidable task. There is currently no
      simple strategy with a rigorous framework. Using an analogy to the exact
      algebraic property for a transition matrix of a master equation in statistical
      physics, we propose a method based on a Laplacian matrix for the discovery and
      prediction of new classes in the unsupervised complex networking phenomena where
      the class of each sample is completely unknown. Using this proposed Laplacian
      approach, we can simultaneously discover different classes and determine the
      identity of each class. Through an illustrative test of the Laplacian approach
      applied to real datasets of gene expression profiles, leukemia data [Golub TR, et
      al. (1999) Science 286:531-537], and lymphoma data [Alizadeh AA, et al. (2000)
      Nature 403:503-511], we demonstrate that this approach is accurate and robust
      with a mathematical and physical realization. It offers a general framework for
      characterizing any kind of complex networking phenomenon in broad areas
      irrespective of whether they are supervised or unsupervised.

PMID- 18337497
TI  - Zebrafish early cardiac connexin, Cx36.7/Ecx, regulates myofibril orientation and
      heart morphogenesis by establishing Nkx2.5 expression.
AB  - Heart development is a precisely coordinated process of cellular proliferation,
      migration, differentiation, and integrated morphogenetic interactions, and
      therefore it is highly susceptible to developmental anomalies such as the
      congenital heart disease (CHD). One of the major causes of CHD has been shown to
      be the mutations in key cardiac transcription factors, including nkx2.5. Here, we
      report the analysis of zebrafish mutant ftk that showed a progressive heart
      malformation in the later stages of heart morphogenesis. Our analyses revealed
      that the cardiac muscle maturation and heart morphogenesis in ftk mutants were
      impaired because of the disorganization of myofibrils. Notably, we found that the
      expression of nkx2.5 was down-regulated in the ftk heart despite the normal
      expression of gata4 and tbx5, suggesting a common mechanism for the occurrence of
      ftk phenotype and CHD. We identified ftk to be a loss-of-function mutation in a
      connexin gene, cx36.7/early cardiac connexin (ecx), expressed during early heart
      development. We further showed by a rescue experiment that Nkx2.5 is the
      downstream mediator of Ecx-mediated signaling. From these results, we propose
      that the cardiac connexin Ecx and its downstream signaling are crucial for
      establishing nkx2.5 expression, which in turn promotes unidirectional, parallel
      alignment of myofibrils and the subsequent proper heart morphogenesis.

PMID- 18337498
TI  - Mutational load distribution analysis yields metrics reflecting genetic
      instability during pancreatic carcinogenesis.
AB  - Considering carcinogenesis as a microevolutionary process, best described in the
      context of metapopulation dynamics, provides the basis for theoretical and
      empirical studies that indicate it is possible to estimate the relative
      contribution of genetic instability and selection to the process of tumor
      formation. We show that mutational load distribution analysis (MLDA) of DNA found
      in pancreatic fluids yields biometrics that reflect the interplay of instability,
      selection, accident, and gene function that determines the eventual emergence of
      a tumor. An in silico simulation of carcinogenesis indicates that MLDA may be a
      suitable tool for early detection of pancreatic cancer. We also present evidence
      indicating that, when performed serially in individuals harboring a p16 germ-line
      mutation bestowing a high risk for pancreatic cancer, MLDA may be an effective
      tool for the longitudinal assessment of risk and early detection of pancreatic
      cancer.

PMID- 18337499
TI  - Anthrax lethal toxin and Salmonella elicit the common cell death pathway of
      caspase-1-dependent pyroptosis via distinct mechanisms.
AB  - Caspase-1 cleaves the inactive IL-1beta and IL-18 precursors into active
      inflammatory cytokines. In Salmonella-infected macrophages, caspase-1 also
      mediates a pathway of proinflammatory programmed cell death termed "pyroptosis."
      We demonstrate active caspase-1 diffusely distributed in the cytoplasm and
      localized in discrete foci within macrophages responding to either Salmonella
      infection or intoxication by Bacillus anthracis lethal toxin (LT). Both stimuli
      triggered caspase-1-dependent lysis in macrophages and dendritic cells.
      Activation of caspase-1 by LT required binding, uptake, and endosome
      acidification to mediate translocation of lethal factor (LF) into the host cell
      cytosol. Catalytically active LF cleaved cytosolic substrates and activated
      caspase-1 by a mechanism involving proteasome activity and potassium efflux. LT
      activation of caspase-1 is known to require the inflammasome adapter Nalp1. In
      contrast, Salmonella infection activated caspase-1 through an independent pathway
      requiring the inflammasome adapter Ipaf. These distinct mechanisms of caspase-1
      activation converged on a common pathway of caspase-1-dependent cell death
      featuring DNA cleavage, cytokine activation, and, ultimately, cell lysis
      resulting from the formation of membrane pores between 1.1 and 2.4 nm in diameter
      and pathological ion fluxes that can be blocked by glycine. These findings
      demonstrate that distinct activation pathways elicit the conserved cell death
      effector mechanism of caspase-1-mediated pyroptosis and support the notion that
      this pathway of proinflammatory programmed cell death is broadly relevant to cell
      death and inflammation invoked by diverse stimuli.

PMID- 18337500
TI  - Genomic imprinting effects on adult body composition in mice.
AB  - Genomic imprinting results in the differential expression of genes, depending on
      which allele is inherited from the mother and which from the father. The effects
      of such differential gene expression are reflected in phenotypic differences
      between the reciprocal heterozygotes (Aa vs. aA). Although many imprinted genes
      have been identified and play a key role in development, little is known about
      the contribution of imprinting to quantitative variation in trait expression.
      Here, we examine this problem by mapping imprinting effects on adult body
      composition traits in the F(3) generation of an intercross between the Large
      (LG/J) and Small (SM/J) inbred mouse strains. We identified eight pleiotropic
      imprinted quantitative trait loci (iQTL) located throughout the genome. Most iQTL
      are in novel locations that have not previously been associated with imprinting
      effects, but those on chromosomes 7, 12, and centromeric 18 lie in regions
      previously identified as containing imprinted genes. Our results show that the
      effects of genomic imprinting are relatively small, with reciprocal heterozygotes
      differing by approximately 0.25 standard deviation units and the effects at each
      locus accounting for 1% to 4% of the phenotypic variance. We detected a variety
      of imprinting patterns, with paternal expression being the most common. These
      results indicate that genomic imprinting has small, but detectable, effects on
      the normal variation of complex traits in adults and is likely to be more common
      than usually thought.

PMID- 18337501
TI  - Heparan sulfate biosynthesis enzymes EXT1 and EXT2 affect NDST1 expression and
      heparan sulfate sulfation.
AB  - Heparan sulfate (HS) proteoglycans influence embryonic development and adult
      physiology through interactions with protein ligands. The interactions depend on
      HS structure, which is determined largely during biosynthesis by Golgi enzymes.
      How biosynthesis is regulated is more or less unknown. During polymerization of
      the HS chain, carried out by a complex of the exostosin proteins EXT1 and EXT2,
      the first modification enzyme, glucosaminyl N-deacetylase/N-sulfotransferase
      (NDST), introduces N-sulfate groups into the growing polymer. Unexpectedly, we
      found that the level of expression of EXT1 and EXT2 affected the amount of NDST1
      present in the cell, which, in turn, greatly influenced HS structure. Whereas
      overexpression of EXT2 in HEK 293 cells enhanced NDST1 expression, increased
      NDST1 N-glycosylation, and resulted in elevated HS sulfation, overexpression of
      EXT1 had opposite effects. Accordingly, heart tissue from transgenic mice
      overexpressing EXT2 showed increased NDST activity. Immunoprecipitaion
      experiments suggested an interaction between EXT2 and NDST1. We speculate that
      NDST1 competes with EXT1 for binding to EXT2. Increased NDST activity in
      fibroblasts with a gene trap mutation in EXT1 supports this notion. These results
      support a model in which the enzymes of HS biosynthesis form a complex, or a
      GAGosome.

PMID- 18337502
TI  - Insulin signaling is involved in the regulation of worker division of labor in
      honey bee colonies.
AB  - It has been proposed that one route of behavioral evolution involves novel
      regulation of conserved genes. Age-related division of labor in honey bee
      colonies, a highly derived behavioral system, involves the performance of
      different feeding-related tasks by different groups of individuals. Older bees
      acquire the colony's food by foraging for nectar and pollen, and the younger
      "nurse" bees feed larvae processed foods. The transition from hive work to
      foraging has been shown to be socially regulated and associated both with
      decreases in abdominal lipid stores and with increases in brain expression of
      genes implicated in feeding behavior in Drosophila melanogaster. Here we show
      that division of labor is influenced by a canonical regulator of food intake and
      energy balance in solitary species, the insulin/insulin-like growth factor
      signaling (IIS) pathway. Foragers had higher levels of IIS gene expression in the
      brain and abdomen than did nurses, despite their low lipid stores. These
      differences are likely nutritionally mediated because manipulations that induced
      low lipid stores in young bees also up-regulated these genes. Changes in IIS also
      causally influenced the timing of behavioral maturation: inhibition of the
      insulin-related target of rapamycin pathway delayed the onset of foraging in a
      seasonally dependent manner. In addition, pathway analyses of microarray data
      revealed that nurses and foragers differ in brain energy metabolism gene
      expression, but the differences are opposite predictions based on their insulin
      signaling status. These results suggest that changes in the regulation of the IIS
      pathway are associated with social behavior.

PMID- 18337503
TI  - Distinct effects of the recurrent Mlh1G67R mutation on MMR functions, cancer, and
      meiosis.
AB  - Mutations in the human DNA mismatch repair (MMR) gene MLH1 are associated with
      hereditary nonpolyposis colorectal cancer (Lynch syndrome, HNPCC) and a
      significant proportion of sporadic colorectal cancer. The inactivation of MLH1
      results in the accumulation of somatic mutations in the genome of tumor cells and
      resistance to the genotoxic effects of a variety of DNA damaging agents. To study
      the effect of MLH1 missense mutations on cancer susceptibility, we generated a
      mouse line carrying the recurrent Mlh1(G67R) mutation that is located in one of
      the ATP-binding domains of Mlh1. Although the Mlh1(G67R) mutation resulted in DNA
      repair deficiency in homozygous mutant mice, it did not affect the MMR-mediated
      cellular response to DNA damage, including the apoptotic response of epithelial
      cells in the intestinal mucosa to cisplatin, which was defective in Mlh1(-/-)
      mice but remained normal in Mlh1(G67R/G67R) mice. Similar to Mlh1(-/-) mice,
      Mlh1(G67R/G67R) mutant mice displayed a strong cancer predisposition phenotype.
      However, in contrast to Mlh1(-/-) mice, Mlh1(G67R/G67R) mutant mice developed
      significantly fewer intestinal tumors, indicating that Mlh1 missense mutations
      can affect MMR tumor suppressor functions in a tissue-specific manner. In
      addition, Mlh1(G67R/G67R) mice were sterile because of the inability of the
      mutant Mlh1(G67R) protein to interact with meiotic chromosomes at pachynema,
      demonstrating that the ATPase activity of Mlh1 is essential for fertility in
      mammals.

PMID- 18337504
TI  - Bystander B cells rapidly acquire antigen receptors from activated B cells by
      membrane transfer.
AB  - The B cell antigen receptor (BCR) efficiently facilitates the capture and
      processing of a specific antigen for presentation on MHC class II molecules to
      antigen-specific CD4(+) T cells (1). Despite this, the majority of B cells are
      thought to play only a limited role in CD4(+) T cell activation because BCRs are
      clonotypically expressed. Here, we show, however, that activated B cells can,
      both in vitro and in vivo, rapidly donate their BCR to bystander B cells, a
      process that is mediated by direct membrane transfer between adjacent B cells and
      is amplified by the interaction of the BCR with a specific antigen. This results
      in a dramatic expansion in the number of antigen-binding B cells in vivo, with
      the transferred BCR endowing recipient B cells with the ability to present a
      specific antigen to antigen-specific CD4(+) T cells.

PMID- 18337505
TI  - Fluorescence resonance energy transfer in near-infrared fluorescent
      oligonucleotide probes for detecting protein-DNA interactions.
AB  - Optical imaging in the near-infrared (NIR) range enables detecting ligand
      receptor interactions and enzymatic activity in vivo due to lower scattering and
      absorption of NIR photons in the tissue. We designed and tested prototype NIR
      fluorescent oligodeoxyribonucleotide (ODN) reporters that can sense transcription
      factor NF-kappaB p50 protein binding. The reporter duplexes included donor NIR
      Cy5.5 indodicarbocyanine fluorochrome linked to the 3' end of the first ODN and
      NIR acceptor fluorochromes (indodicarbocyanine Cy7 or, alternatively, a
      heptamethine cyanine IRDye 800CW) that were linked at the positions +8 and +12 to
      the complementary ODN that encoded p50 binding sites. Both Cy7 and 800CW
      fluorochromes were linked by using hydrophilic internucleoside phosphate linkers
      that enable interaction between the donor and the acceptor with no base-pairing
      interference. We observed efficient fluorescence resonance energy transfer (FRET)
      both in the case of Cy5.5-Cy7 and Cy5.5-800CW pairs of fluorochromes, which was
      sensitive to the relative position of the dyes. Higher FRET efficiency observed
      in the case of Cy5.5-Cy7 pair was due to a larger overlap between the ODN-linked
      Cy5.5 emission and Cy7 excitation spectra. Fluorescent mobility shift assay
      showed that the addition of human recombinant p50 to ODN duplexes resulted in p50
      binding and measurable increase of Cy5.5 emission. In addition, p50 binding
      provided a concomitant protection of FRET effect from exonuclease-mediated
      hydrolysis. We conclude that NIR FRET effect can be potentially used for
      detecting protein-DNA interactions and that the feasibility of detection depends
      on FRET efficacy and relative fluorochrome positions within ODN binding sites.

PMID- 18337506
TI  - Comparative lesion sequencing provides insights into tumor evolution.
AB  - We show that the times separating the birth of benign, invasive, and metastatic
      tumor cells can be determined by analysis of the mutations they have in common.
      When combined with prior clinical observations, these analyses suggest the
      following general conclusions about colorectal tumorigenesis: (i) It takes
      approximately 17 years for a large benign tumor to evolve into an advanced cancer
      but <2 years for cells within that cancer to acquire the ability to metastasize;
      (ii) it requires few, if any, selective events to transform a highly invasive
      cancer cell into one with the capacity to metastasize; (iii) the process of cell
      culture ex vivo does not introduce new clonal mutations into colorectal tumor
      cell populations; and (iv) the rates at which point mutations develop in advanced
      cancers are similar to those of normal cells. These results have important
      implications for understanding human tumor pathogenesis, particularly those
      associated with metastasis.

PMID- 18337507
TI  - A preclinical model for predicting drug response in soft-tissue sarcoma with
      targeted AAVP molecular imaging.
AB  - Human sarcomas are rare but diverse malignant tumors derived from mesenchymal
      tissue. Clinical response to therapy is currently determined by the modified
      World Health Organization (WHO) criteria or the Response Evaluation Criteria in
      Solid Tumors (RECIST), but these standards correlate poorly with sarcoma patient
      outcome. We introduced ligand-directed particles with elements of AAV and phage
      (AAVP) to enable integration of tumor targeting to molecular imaging. We report
      drug-response monitoring and prediction in a nude rat model of human sarcoma by
      AAVP imaging. As a proof-of-concept, we imaged Herpes simplex thymidine kinase in
      a clinic-ready setting with PET to show that one can a priori predict tumor
      response to a systemic cytotoxic. Given the target expression in patient-derived
      sarcomas, this platform may be translated in clinical applications. Sarcoma
      specific ligands and promoters may ultimately lead to an imaging transcriptome.

PMID- 18337509
TI  - PPARdelta regulates multiple proinflammatory pathways to suppress
      atherosclerosis.
AB  - Lipid homeostasis and inflammation are key determinants in atherogenesis,
      exemplified by the requirement of lipid-laden, foam cell macrophages for
      atherosclerotic lesion formation. Although the nuclear receptor PPARdelta has
      been implicated in both systemic lipid metabolism and macrophage inflammation,
      its role as a therapeutic target in vascular disease is unclear. We show here
      that orally active PPARdelta agonists significantly reduce atherosclerosis in
      apoE(-/-) mice. Metabolic and gene expression studies reveal that PPARdelta
      attenuates lesion progression through its HDL-raising effect and anti
      inflammatory activity within the vessel wall, where it suppresses chemoattractant
      signaling by down-regulation of chemokines. Activation of PPARdelta also induces
      the expression of regulator of G protein signaling (RGS) genes, which are
      implicated in blocking the signal transduction of chemokine receptors. Consistent
      with this, PPARdelta ligands repress monocyte transmigration and macrophage
      inflammatory responses elicited by atherogenic cytokines. These results reveal
      that PPARdelta antagonizes multiple proinflammatory pathways and suggest
      PPARdelta-selective drugs as candidate therapeutics for atherosclerosis.

PMID- 18337510
TI  - Auxin transport inhibitors impair vesicle motility and actin cytoskeleton
      dynamics in diverse eukaryotes.
AB  - Many aspects of plant development, including patterning and tropisms, are largely
      dependent on the asymmetric distribution of the plant signaling molecule auxin.
      Auxin transport inhibitors (ATIs), which interfere with directional auxin
      transport, have been essential tools in formulating this concept. However,
      despite the use of ATIs in plant research for many decades, the mechanism of ATI
      action has remained largely elusive. Using real-time live-cell microscopy, we
      show here that prominent ATIs such as 2,3,5-triiodobenzoic acid (TIBA) and 2-(1
      pyrenoyl) benzoic acid (PBA) inhibit vesicle trafficking in plant, yeast, and
      mammalian cells. Effects on micropinocytosis, rab5-labeled endosomal motility at
      the periphery of HeLa cells and on fibroblast mobility indicate that ATIs
      influence actin cytoskeleton. Visualization of actin cytoskeleton dynamics in
      plants, yeast, and mammalian cells show that ATIs stabilize actin. Conversely,
      stabilizing actin by chemical or genetic means interferes with endocytosis,
      vesicle motility, auxin transport, and plant development, including auxin
      transport-dependent processes. Our results show that a class of ATIs act as actin
      stabilizers and advocate that actin-dependent trafficking of auxin transport
      components participates in the mechanism of auxin transport. These studies also
      provide an example of how the common eukaryotic process of actin-based vesicle
      motility can fulfill a plant-specific physiological role.

PMID- 18337508
TI  - Production and sequence validation of a complete full length ORF collection for
      the pathogenic bacterium Vibrio cholerae.
AB  - Cholera, an infectious disease with global impact, is caused by pathogenic
      strains of the bacterium Vibrio cholerae. High-throughput functional proteomics
      technologies now offer the opportunity to investigate all aspects of the
      proteome, which has led to an increased demand for comprehensive protein
      expression clone resources. Genome-scale reagents for cholera would encourage
      comprehensive analyses of immune responses and systems-wide functional studies
      that could lead to improved vaccine and therapeutic strategies. Here, we report
      the production of the FLEXGene clone set for V. cholerae O1 biovar eltor str.
      N16961: a complete-genome collection of ORF clones. This collection includes
      3,761 sequence-verified clones from 3,887 targeted ORFs (97%). The ORFs were
      captured in a recombinational cloning vector to facilitate high-throughput
      transfer of ORF inserts into suitable expression vectors. To demonstrate its
      application, approximately 15% of the collection was transferred into the
      relevant expression vector and used to produce a protein microarray by
      transcribing, translating, and capturing the proteins in situ on the array
      surface with 92% success. In a second application, a method to screen for protein
      triggers of Toll-like receptors (TLRs) was developed. We tested in vitro
      synthesized proteins for their ability to stimulate TLR5 in A549 cells. This
      approach appropriately identified FlaC, and previously uncharacterized TLR5
      agonist activities. These data suggest that the genome-scale, fully sequenced ORF
      collection reported here will be useful for high-throughput functional proteomic
      assays, immune response studies, structure biology, and other applications.

PMID- 18337511
TI  - NFAR-1 and -2 modulate translation and are required for efficient host defense.
AB  - We report here that the alternatively spliced nuclear factors associated with
      double-stranded RNA, NFAR-1 (90 kDa) and -2 (110 kDa), are involved in retaining
      cellular transcripts in intranuclear foci and can regulate the export of mRNA to
      the cytoplasm. Furthermore, the NFAR proteins were found to remain associated
      with exported ribonucleoprotein complexes. Loss of NFAR function, which was
      embryonic-lethal, caused an increase in protein synthesis rates, an effect
      augmented by the presence of the mRNA export factors TAP, p15, or Rae1.
      Significantly, NFAR depletion in normal murine fibroblasts rendered these cells
      dramatically susceptible to vesicular stomatitis virus replication. Collectively,
      our data demonstrate that the NFARs exert influence on mRNA trafficking and the
      modulation of translation rates and may constitute an innate immune translational
      surveillance mechanism important in host defense countermeasures against virus
      infection.

PMID- 18337512
TI  - Size, foraging, and food web structure.
AB  - Understanding what structures ecological communities is vital to answering
      questions about extinctions, environmental change, trophic cascades, and
      ecosystem functioning. Optimal foraging theory was conceived to increase such
      understanding by providing a framework with which to predict species interactions
      and resulting community structure. Here, we use an optimal foraging model and
      allometries of foraging variables to predict the structure of real food webs. The
      qualitative structure of the resulting model provides a more mechanistic basis
      for the phenomenological rules of previous models. Quantitative analyses show
      that the model predicts up to 65% of the links in real food webs. The
      deterministic nature of the model allows analysis of the model's successes and
      failures in predicting particular interactions. Predacious and herbivorous
      feeding interactions are better predicted than pathogenic, parasitoid, and
      parasitic interactions. Results also indicate that accurate prediction and
      modeling of some food webs will require incorporating traits other than body size
      and diet choice models specific to different types of feeding interaction. The
      model results support the hypothesis that individual behavior, subject to natural
      selection, determines individual diets and that food web structure is the sum of
      these individual decisions.

PMID- 18337513
TI  - Controlling the rates of biochemical reactions and signaling networks by shape
      and volume changes.
AB  - In biological systems, chemical activity takes place in micrometer- and nanometer
      sized compartments that constantly change in shape and volume. These ever
      changing cellular compartments embed chemical reactions, and we demonstrate that
      the rates of such incorporated reactions are directly affected by the ongoing
      shape reconfigurations. First, we show that the rate of product formation in an
      enzymatic reaction can be regulated by simple volume contraction-dilation
      transitions. The results suggest that mitochondria may regulate the dynamics of
      interior reaction pathways (e.g., the Krebs cycle) by volume changes. We then
      show the effect of shape changes on reactions occurring in more complex and
      structured systems by using biomimetic networks composed of micrometer-sized
      compartments joined together by nanotubes. Chemical activity was measured by
      implementing an enzymatic reaction-diffusion system. During ongoing reactions,
      the network connectivity is changed suddenly (similar to the dynamic tube
      formations found inside Golgi stacks, for example), and the effect on the
      reaction is registered. We show that spatiotemporal properties of the reaction
      diffusion system are extremely sensitive to sudden changes in network topology
      and that chemical reactions can be initiated, or boosted, in certain nodes as a
      function of connectivity.

PMID- 18337514
TI  - Reply to Pape et al.: the phylogeography of HIV-1 group M subtype B.

PMID- 18337515
TI  - Inhibition of rat oocyte maturation and ovulation by nitric oxide: mechanism of
      action.
AB  - Established gap junctional communication (GJC) in the ovarian follicle is
      essential for maintaining the oocytes in meiotic arrest. Alternatively, LH
      induced reinitiation of meiosis is subsequent to breakdown of GJC. It was
      recently reported that nitric oxide (NO) inhibits maturation in rat follicle
      enclosed oocytes and elevates GJC in cultured mesangial cells. Taking these
      observations into account, we hypothesized that NO prevents reinitiation of
      meiosis by antagonizing the effect of LH on GJC in the ovarian follicle. Indeed,
      we found that NO interferes with LH-induced disruption of GJC as well as with the
      decrease of the expression of the gap junction protein GJA1 (previously known as
      CONNEXIN43). We also demonstrated that NO prevents activation of LH-induced
      mitogen-activated protein kinases (MAPKs) 1 and 2 and inhibits cumulus expansion.
      Along this line, incubation of ovarian follicles with an inhibitor of soluble
      guanylate cyclase, which is a downstream NO effector, induced on its own oocyte
      maturation as well as cumulus expansion. Unlike previous studies, we show here
      that elevation of NO resulted in inhibition of ovulation. We conclude that the
      mechanism by which NO inhibits LH-induced oocyte maturation possibly involves a
      negative effect on MAPK activation and, in turn, interference with interruption
      of GJC. This action of NO in the ovarian follicle is apparently mediated by cGMP.
      In addition, the negative effect of NO on ovulation may be subsequent to its
      inhibitory effect on cumulus expansion. Together, this study suggests that the
      preovulatory decrease in NO concentrations is a prerequisite for the ovarian
      response to LH.

PMID- 18337516
TI  - Interleukin 1 signaling is regulated by leukemia inhibitory factor (LIF) and is
      aberrant in Lif-/- mouse uterus.
AB  - This study addresses the regulation of the interleukin 1 (IL1) system in the
      murine uterine luminal epithelium (LE) and stroma by leukemia inhibitory factor
      (LIF). Using RT-PCR we compared expression of Il1a, Il1b, Il1rn, Il1r1, and Il1r2
      during the pre- and peri-implantation periods of pregnancy in wild-type (WT) and
      LIF-null LE and stroma. In WT LE, Il1a transcripts were down-regulated on Day 4
      of pregnancy (D4), with renewed expression by the evening of D4 (D4 pm). In Lif(
      /-) LE there was a gradual decrease in expression on D2, and expression became
      undetectable by D6. Il1b and Il1r1 expression were similar in WT and null mice,
      but Il1rn expression was almost completely lost during the peri-implantation
      period in Lif(-/-) LE. In the stroma, Il1a was sharply down-regulated on D4 and
      reappeared on D4 pm but was only expressed from D3 to D5 in the null mice.
      Stromal Il1r1 and Il1r2 were also misregulated. Il1rn showed constitutive
      expression in null stroma in contrast to the loss of expression on D4 in the WT
      mouse. In Lif-deficient mice, immunostaining indicated a reduction of endometrial
      IL1A at the time of implantation and of IL1B in stroma. LE-stromal coculture
      revealed that LIF stimulated the apical secretion of both IL1A and PTGES2 by LE
      cells without affecting basal secretion of IL1A and with only a small effect on
      basal PTGES2 secretion. We conclude that Il1a and Il1rn in LE and Il1a, Il1rn,
      and Il1r1 in stroma are regulated by LIF, which stimulates apical secretion of
      IL1A by LE.

PMID- 18337517
TI  - The gift of grace.

PMID- 18337518
TI  - [Are family physicians on the road to extinction?].

PMID- 18337519
TI  - Climbing the walls: Structural barriers to accessing primary care for refugee
      newcomers in Canada.

PMID- 18337521
TI  - Rebuttal: Do you approve of spending $300 million on HPV vaccination? Yes.

PMID- 18337522
TI  - Rebuttal: Do you approve of spending $300 million on HPV vaccination? No.

PMID- 18337525
TI  - Addictive evidence.

PMID- 18337526
TI  - Is the use of letrozole to induce ovulation teratogenic?
AB  - QUESTION: A patient of mine has been prescribed letrozole to induce ovulation;
      however, a recent release from the Food and Drug Administration contraindicates
      the use of letrozole in premenopausal women owing to teratogenicity. Does the use
      of letrozole increase the risk of a child being born with a birth defect? ANSWER:
      The use of letrozole to induce ovulation has not been associated with an
      increased risk of a child being born with a birth defect; in contrast, the use of
      clomiphene citrate in pregnancy is associated with intrauterine growth
      restriction.

PMID- 18337527
TI  - Dermacase. Pretibial myxedema.

PMID- 18337528
TI  - Practice tips. Improving hypertension management in my practice.

PMID- 18337529
TI  - Treating frostbite.

PMID- 18337530
TI  - Hereditary angioedema and pregnancy: a successful outcome using C1 esterase
      inhibitor concentrate.

PMID- 18337531
TI  - Treatment of herpes zoster.
AB  - OBJECTIVE: To review the evidence regarding treatment of herpes zoster (HZ) in
      the short-term, focusing on the prevention of postherpetic neuralgia (PHN).
      QUALITY OF EVIDENCE: The evidence relating to treatment of HZ is derived mainly
      from randomized controlled trials (level I evidence). MAIN MESSAGE: Antiviral
      drugs might have some effect on the severity of acute pain and on the duration of
      skin lesions. Corticosteroids also alleviate acute pain. Oral antiviral
      medication reduces the risk of eye complications in patients with ophthalmic HZ.
      There is no convincing evidence that antiviral medication reduces the risk of
      PHN. Some studies, however, have shown that famciclovir and valacyclovir shorten
      the duration of PHN. The effectiveness of amitriptyline or cutaneous and
      percutaneous interventions in preventing PHN has not been proven. CONCLUSION:
      Oral antiviral drugs should be prescribed to elderly HZ patients with high risk
      of PHN. Moreover, these drugs should be prescribed to all patients at the first
      signs of ophthalmic HZ, irrespective of age or severity of symptoms.

PMID- 18337532
TI  - Same-day booking: success in a Canadian family practice.
AB  - PROBLEM BEING ADDRESSED: Patients in a family practice had to wait 6 weeks for an
      appointment. OBJECTIVE OF PROGRAM: To improve patient care by facilitating access
      to timely appointments. PROGRAM DESCRIPTION: An FP from Halifax, NS, implemented
      advanced access in her practice. Advanced access is a same-day booking system,
      which has been shown to reduce or eliminate patient backlogs without the addition
      of resources. Theoretically, it can be put into effect in any practice with a
      stable backlog (which indicates that supply and demand are well matched). The
      first step to implement the advanced access system was to clear the existing
      appointment backlog. During a 6-week "boot camp" period, all prebooked patients
      and patients who called requesting same-day appointments were seen (between 50
      and 60 patients per day). Same-day appointment rules apply to almost all
      patients. Staff begin accepting calls at 8:00 AM, and patients request the most
      convenient time available. CONCLUSION: Baseline and postimplementation data are
      not available, as this was not a formal research study. Nevertheless, this FP
      from Halifax who implemented advanced access experienced the following in her
      practice: elimination of patient backlog, fewer no-shows, patients' happiness
      with the system, increase in physician and staff morale, and stability in
      physician income. Formal feasibility studies and research evaluating patient
      outcomes, cost effectiveness, and physician and patient satisfaction in a variety
      of practice settings would help Canadian FPs decide if same-day booking could be
      successfully implemented in their practices.

PMID- 18337533
TI  - Do patients' expectations influence their use of medications? Qualitative study.
AB  - OBJECTIVE: To investigate whether patients' expectations influence how they take
      their medications by looking at the expectations patients have of their
      medications and the factors that affect these expectations. DESIGN: Qualitative
      study using in-depth interviews and a grounded-theory approach. SETTING: A large
      city in Ontario. PARTICIPANTS: A total of 18 community-dwelling adult patients
      taking medication for at least 6 months. METHOD: Both purposive and convenience
      sampling techniques were used. The initial strategy comprised stratified, maximum
      variation, and typical case sampling. The research team developed a
      semistructured interview guide after a preliminary review of the literature.
      Individual, face-to-face, in-depth interviews were conducted and audiotaped. At
      the end of the interviews, basic demographic information was collected.
      Interviewers were debriefed following each interview and their comments on
      relevant contextual information, general impressions of the interview, and
      possible changes to the interview guide were audiotaped. Audiotapes of each
      interview, including the debriefing, were transcribed verbatim, cleaned, and
      given a unique identifying number. At least 2 team members participated in
      analyzing the data using an operational code book that was modified to
      accommodate emerging themes as analysis continued. MAIN FINDINGS: Patients'
      expectations were more realistic than idealistic. Many participants acted on
      their expectations by changing their medication regimens on their own or by
      seeking additional information on their medications. Expectations were affected
      by patients' beliefs, past experiences with medications, relationships with their
      health care providers, other people's beliefs, and the cost of medication.
      Patients actively engaged in strategies to confirm or modify their expectations
      of their medications. CONCLUSION: A range of factors (most notably past
      experiences with medications and relationships with health care providers)
      influenced patients' expectations of their medications. More comprehensive
      discussion between patients and their health care providers about these factors
      could affect whether medications are used optimally.

PMID- 18337534
TI  - Patients' adherence to osteoporosis therapy: exploring the perceptions of
      postmenopausal women.
AB  - OBJECTIVE: To explore the experiences and perceptions of postmenopausal women
      regarding strategies to improve adherence to osteoporosis therapy. DESIGN:
      Qualitative, mixed phenomenologic study using focus groups. SETTING: Family
      physicians' and specialists' practices and community pharmacies in Hamilton, Ont.
      PARTICIPANTS: A total of 37 postmenopausal women currently taking at least 1
      prescription or over-the-counter medication for osteoporosis. METHOD: Focus
      groups were conducted using a semistructured interview guide consisting of 10
      open-ended questions about patients' perceptions of their osteoporosis
      medications, their reasons for adherence and non-adherence to therapy, and the
      effectiveness of strategies they had tried to improve adherence. At least 2
      research team members analyzed the data to find primary themes. MAIN FINDINGS:
      Analysis of data from the 7 focus groups found 6 main factors that influenced
      adherence to medications: belief in the importance of taking medications for
      osteoporosis, medication-specific factors, beliefs regarding medications and
      health, relationships with health care providers, information exchange, and
      strategies to improve adherence. Strategies that facilitated adherence to
      medications included having a system for taking medications, using cues or
      reminders, being well informed about the reasons for taking medications, and
      having regular follow-up by health care providers for support and monitoring
      after having been prescribed medications. CONCLUSION: Results of this study
      provide a better understanding of how patients' perceptions and experiences
      affect their adherence to osteoporosis medications. Because each patient's
      reasons for non-adherence might be different, depending on individual beliefs or
      circumstances, strategies to improve adherence to medications should be
      individualized accordingly.

PMID- 18337535
TI  - Which patients receive advice on diet and exercise? Do certain characteristics
      affect whether they receive such advice?
AB  - OBJECTIVE: To examine whether patients' characteristics, familiarity with the
      clinic, or perspectives on the quality of their care predict whether they receive
      advice from physicians regarding diet and exercise. DESIGN: Secondary data
      analysis of responses to the Primary Care Practice Survey. SETTING: Capital
      District Health Authority in Nova Scotia. PARTICIPANTS: Residents of the Capital
      District Health Authority 18 years old and older (N = 1562). MAIN OUTCOME
      MEASURES: Percentage of patients who reported frequently receiving advice from
      their family physicians regarding diet and exercise. RESULTS: Almost 38% of
      respondents reported frequently receiving advice from their physicians on diet.
      Those more likely to receive advice on diet were male (adjusted odds ratio [AOR]
      1.6, 95% confidence interval [CI] 1.2 to 2.1), were 35 to 54 years old (compared
      with those aged 18 to 34) (AOR 1.5, 95% CI 1.1 to 2.2), had more chronic
      illnesses (AOR 1.3, 95% CI 1.2 to 1.6), had good relationships with their health
      care providers (AOR 2.3, 95% CI 1.8 to 3.1), or reported higher scores on an
      enablement scale (AOR 2.2, 95% CI 1.6 to 3.1). Respondents who reported their
      health status as excellent were less likely to receive advice on diet (AOR 0.5,
      95% CI 0.3 to 0.9). About 42% of respondents reported frequently receiving advice
      on exercise. Men (AOR 1.7, 95% CI 1.3 to 2.2), those older than 35 years (AOR
      1.7, 95% CI 1.2 to 2.4 for those aged 35 to 54; AOR 1.6, 95% CI 1.1 to 2.3 for
      those 55 and older), those rating their health as good (AOR 1.6, 95% CI 1.1 to
      2.4), those with more chronic illnesses (AOR 1.3, 95% CI 1.1 to 1.5), and those
      reporting higher scores on communication (AOR 3.2, 95% CI 2.3 to 4.4) and
      enablement (AOR 1.8, 95% CI 1.3 to 2.4) scales were more likely to receive advice
      on exercise. CONCLUSION: Strategies to increase the number of patients who
      receive advice on diet and exercise would likely include enhancing communication
      between patients and their physicians, improving relationships between patients
      and their physicians, and improving physicians' ability to help their patients
      feel enabled to act on advice and cope with their illnesses. Physicians should be
      aware of their counseling practices and consider discussing healthy behaviour
      with patients with no obvious risk factors. This would be practising true primary
      prevention.

PMID- 18337536
TI  - Family physicians' attitudes toward education in research skills during
      residency: findings from a national mailed survey.
AB  - OBJECTIVE: To determine the attitudes of practising Canadian family physicians
      toward education in research skills during residency, to identify what determines
      these attitudes, and to investigate the effect of education in research skills on
      future research activity. DESIGN: Mailed survey. SETTING: Primary care.
      PARTICIPANTS: Stratified random sample of 247 practising physicians who were
      members of the College of Family Physicians of Canada. MAIN OUTCOME MEASURES:
      Physicians' attitudes toward education in research skills during residency, their
      perceptions of the value of research in primary care, and their current
      involvement in research activities. RESULTS: Overall response rate was 56%.
      Nearly all respondents agreed that critical appraisal skills are essential to the
      practice of modern family medicine. Most agreed that it is very important that
      the evidence base for primary care medicine be developed by family physicians,
      yet only one-third agreed that research skills ought to receive more emphasis
      during residency training, and fewer than one-quarter agreed that practising
      family physicians should have strong research skills. Fewer than half the
      respondents agreed that a core goal of family medicine residency training should
      be to promote and develop an active interest in research. While three-quarters
      agreed that research projects during residency can be formative learning
      experiences, only about 40% indicated that research projects should be required,
      and only about 20% considered their own resident research projects to have been
      highly influential learning experiences. Respondents whose residency programs had
      research in the curriculum were significantly more likely to have found their
      research projects to be highly influential learning experiences (P <.05), and
      those who had successfully completed research projects were less likely to
      believe that they lacked the necessary skills and expertise to conduct their own
      research studies. Those who had successfully completed resident research projects
      participated in postresidency research activity at a significantly higher rate
      than those who did not complete projects (P <.01). CONCLUSION: Despite a
      conviction that research is important in primary care, only a few practising
      family physicians in our sample believed that strong research skills are
      important or that education in research skills should receive more emphasis
      during residency training. Resident research projects are not invariably
      influential learning experiences, although some evidence indicates that
      successful completion of a project makes future participation in research more
      likely.

PMID- 18337537
TI  - Influenza.

PMID- 18337539
TI  - A transformational journey.

PMID- 18337540
TI  - Measuring success.

PMID- 18337542
TI  - Family physician shortages: are nurses the answer?

PMID- 18337544
TI  - Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with
      disrupted type IIa sodium-phosphate cotransporter.
AB  - The most common theories about the pathogenesis of idiopathic kidney stones
      consider precipitation of calcium phosphate (CaP) within the kidneys critical for
      the development of the disease. We decided to test the hypothesis that a CaP
      substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys.
      Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with
      knockout (KO) of NaP(i) IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO
      mice are hypercalciuric and produce CaP deposits in their renal tubules.
      Experimental hyperoxaluria led to CaOx crystalluria in both the hypercalciuric KO
      mice and the normocalciuric control B6 mice. Only the KO mice produced CaOx
      crystal deposits in their kidneys, but the CaOx crystals deposited separately
      from the CaP deposits. Perhaps CaP deposits were not available for a CaOx
      overgrowth. These results also validate earlier animal model observations that
      showed that CaP substrate is not required for renal deposition of CaOx and that
      other factors, such as local supersaturation, may be involved. The absence of
      CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the
      importance of both calcium and oxalate in the development of CaOx
      nephrolithiasis.

PMID- 18337545
TI  - Angiotensin II increases the expression of the transcription factor ETS-1 in
      mesangial cells.
AB  - Maladaptive activation of the renin-angiotensin system (RAS) has been shown to
      play a critical role in the pathogenesis of chronic kidney disease. Reactive
      oxygen species (ROS) are critical signals for many of the nonhemodynamic effects
      of angiotensin II (ANG II). We have demonstrated that ANG II increases mesangial
      and cortical cyclooxygenase-2 (COX-2) expression and activity via NADPH oxidase
      derived ROS. The transcription factor ETS-1 (E26 transformation-specific
      sequence) has been identified as a critical regulator of growth-related responses
      and inflammation. The present studies were designed to determine: 1) whether ANG
      II induces ETS-1 expression in vitro in cultured rat mesangial cells and in vivo
      in rats infused with ANG II; and 2) whether ROS and COX-2 are mediators of ETS-1
      induction in response to ANG II. Mesangial cells stimulated with ANG II (10(-7)
      M) exhibited a significant increase in ETS-1 expression that was prevented by the
      angiotensin type 1 receptor blocker candesartan. NADPH oxidase inhibition with
      dyphenilene iodinium or apocynin also prevented ETS-1 induction, establishing the
      role of ROS as mediators of ETS-1 expression in response to ANG II. COX-2
      inhibition prevented ETS-1 expression in response to ANG II, suggesting that COX
      2 is required for ETS-1 induction. By utilizing short interfering RNAs against
      ETS-1, we have also determined that ETS-1 is required to induce the production of
      fibronectin in response to ANG II. Furthermore, rats infused with ANG II
      manifested increased glomerular expression of ETS-1. These studies unveil novel
      pathways that may play an important role in the pathogenesis of renal injury when
      RAS is activated.

PMID- 18337546
TI  - Identification and subcellular localization of a new cystinosin isoform.
AB  - Nephropathic cystinosis is a lysosomal disorder caused by functional defects of
      cystinosin, which mediates cystine efflux into the cytosol. The protein sequence
      contains at least two signals that target the protein to the lysosomal
      compartment, one of which is located at the carboxy terminal tail (GYDQL). We
      have isolated from a human kidney cDNA library a cystinosin isoform, which is
      generated by an alternative splicing of exon 12 that removes the GYDQL motif.
      Based on its last three amino acids, we have termed this protein cystinosin-LKG.
      Contrary to the lysosomal cystinosin isoform, expression experiments performed by
      transient transfection of green fluorescent protein fusion plasmids in HK2 cells
      showed that cystinosin-LKG is expressed in the plasma membrane, in lysosomes, and
      in other cytosolic structures. This subcellular localization of the protein was
      confirmed by transmission electron microscopy. In addition, immunogold labeling
      was observed in the endoplasmic reticulum and in the Golgi apparatus. Expression
      of the protein in renal tubular structures was also directly demonstrated by
      immunostaining of normal human kidney sections. The plasma membrane localization
      of cystinosin-LKG was directly tested by [(35)S]cystine flux experiments in COS-1
      cells. In the presence of a proton gradient, a marked enhancement of
      intracellular cystine transport was observed in cells overexpressing this
      isoform. These data indicate that the expression of the gene products encoded by
      the CTNS gene is not restricted to the lysosomal compartment. These finding may
      help elucidate the mechanisms of cell dysfunction in this disorder.

PMID- 18337547
TI  - MKL1 mediates TGF-beta1-induced alpha-smooth muscle actin expression in human
      renal epithelial cells.
AB  - Transforming growth factor-beta1 (TGF-beta1) is known to induce epithelial
      mesenchymal transition in the kidney, a process involved in tubulointerstitial
      fibrosis. We hypothesized that a coactivator of the serum response factor (SRF),
      megakaryoblastic leukemia factor-1 (MKL1), stimulates alpha-smooth muscle actin
      (alpha-SMA) transcription in primary cultures of renal tubular epithelial cells
      (RTC), which convert into myofibroblasts on treatment with TGF-beta1. Herein, we
      study the effect of MKL1 expression on alpha-SMA in these cells. We demonstrate
      that TGF-beta1 stimulation of alpha-SMA transcription is mediated through
      CC(A/T)(6)-rich GG elements known to bind to SRF. These elements also mediate the
      MKL1 effect that dramatically activates alpha-SMA transcription in serum-free
      media. MKL1 fused to green fluorescent protein localizes to the nucleus and
      induces alpha-SMA expression regardless of treatment with TGF-beta1. Using
      proteasome inhibitors, we also demonstrate that the proteolytic ubiquitin pathway
      regulates MKL1 expression. These data indicate that MKL1 overexpression is
      sufficient to induce alpha-SMA expression. Inhibition of endogenous expression of
      MKL1 by small interfering RNA abolishes TGF-beta1 stimulation of alpha-SMA
      expression. Therefore, MKL1 is also absolutely required for TGF-beta1 stimulation
      of alpha-SMA expression. Western blot and immunofluorescence analysis show that
      overexpressed and endogenous MKL1 are located in the nucleus in non-stimulated
      RTC. Chromatin immunoprecipitation assay demonstrates that TGF-beta1 induces
      binding of endogenous SRF and MKL1 to the alpha-SMA promoter in chromatin. Since
      MKL1 constitutes a potent factor regulating alpha-SMA expression, modulation of
      endogenous MKL1 expression or activity may have a profound effect on
      myofibroblast formation and function in the kidney.

PMID- 18337548
TI  - Q-methodology in nursing research: a promising method for the study of
      subjectivity.
AB  - This article provides an overview and application of Q-methodology for nursing
      researchers, with an illustration of its appropriate usage. Q-methodology has
      been identified as a method for the analysis of subjective viewpoints and has the
      strengths of both qualitative and quantitative methods. It shares with
      qualitative methodologies the aim of exploring subjectivity; however, statistical
      techniques are used to reveal the structure of views. This article describes the
      use of Q-methodology to examine subjectivity systematically, revealing
      connections between accounts that other techniques may overlook. An example from
      the literature is presented. Q-methodology is useful in qualitative nursing
      research concerned with the exploration and comparison of subjectivity and
      attitudes. It can be used to effectively identify attitudes, perceptions,
      feelings, and values as well as explore life experiences such as stress, self
      esteem, body image, and satisfaction.

PMID- 18337549
TI  - Addition of plasmapheresis decreases the incidence of acute antibody-mediated
      rejection in sensitized patients with strong donor-specific antibodies.
AB  - BACKGROUND AND OBJECTIVES: The objective of this study was to investigate the
      effects of desensitization protocols using intravenous Ig with or without
      plasmapheresis in patients with donor-specific anti-HLA antibodies on prevention
      of antibody-mediated rejection and downregulation of donor-specific antibodies.
      DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Thirty-five complement-dependent
      cytotoxicity T cell cross-match-negative but complement-dependent cytotoxicity B
      cell and/or flow cytometry cross-match-positive kidney transplant recipients were
      treated with high-dosage intravenous Ig plus Thymoglobulin induction treatment.
      Donor-specific antibody strength was stratified as strong, medium, or weak by
      Luminex flow beads. Group 1 patients had weak/moderate and group 2 strong donor
      specific antibodies RESULTS: Whereas no group 1 patients had acute rejection, 66%
      of group 2 had acute rejection (44% antibody-mediated rejection, 22% cellular
      rejection). The protocol was then changed to the addition of peritransplantation
      plasmapheresis to patients with strong donor-specific antibodies (group 3). This
      change resulted in a dramatic decrease in the acute rejection rate to 7%. During
      a median 18 mo of follow-up, patient survival was 100, 100, and 93% and graft
      survival was 100, 78, and 86% in groups 1, 2, and 3, respectively. During follow
      up, 17 (52%) patients lost donor-specific antibodies completely, and 10 (30%)
      lost some of donor-specific antibodies and/or decreased the strength of existing
      donor-specific antibodies. CONCLUSIONS: These results indicated that in patients
      with strong donor-specific antibodies, the addition of plasmapheresis to high
      dosage intravenous Ig decreases the incidence of acute rejection. The majority of
      the patients, whether they received intravenous Ig alone or with plasmapheresis,
      lost their donor-specific antibodies during follow-up.

PMID- 18337550
TI  - Diagnosis, epidemiology and outcomes of acute kidney injury.
AB  - Acute kidney injury is an increasingly common and potentially catastrophic
      complication in hospitalized patients. Early observational studies from the 1980s
      and 1990s established the general epidemiologic features of acute kidney injury:
      the incidence, prognostic significance, and predisposing medical and surgical
      conditions. Recent multicenter observational cohorts and administrative databases
      have enhanced our understanding of the overall disease burden of acute kidney
      injury and trends in its epidemiology. An increasing number of clinical studies
      focusing on specific types of acute kidney injury (e.g., in the setting of
      intravenous contrast, sepsis, and major surgery) have provided further details
      into this heterogeneous syndrome. Despite our sophisticated understanding of the
      epidemiology and pathobiology of acute kidney injury, current prevention
      strategies are inadequate and current treatment options outside of renal
      replacement therapy are nonexistent. This failure to innovate may be due in part
      to a diagnostic approach that has stagnated for decades and continues to rely on
      markers of glomerular filtration (blood urea nitrogen and creatinine) that are
      neither sensitive nor specific. There has been increasing interest in the
      identification and validation of novel biomarkers of acute kidney injury that may
      permit earlier and more accurate diagnosis. This review summarizes the major
      epidemiologic studies of acute kidney injury and efforts to modernize the
      approach to its diagnosis.

PMID- 18337551
TI  - Mesna for treatment of hyperhomocysteinemia in hemodialysis patients: a placebo
      controlled, double-blind, randomized trial.
AB  - BACKGROUND AND OBJECTIVES: Increased plasma total homocysteine is a graded,
      independent risk factor for the development of atherosclerosis and thrombosis.
      More than 90% of patients with end-stage renal disease have hyperhomocysteinemia
      despite vitamin supplementation. It was shown in previous studies that a single
      intravenous dose of mesna 5 mg/kg caused a drop in plasma total homocysteine that
      was significantly lower than predialysis levels 2 d after dosing. It was
      hypothesized 5 mg/kg intravenous mesna administered thrice weekly, before
      dialysis, for 8 wk would cause a significant decrease in plasma total
      homocysteine compared with placebo. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: Patients with end-stage renal disease were randomly assigned to
      receive either intravenous mesna 5 mg/kg or placebo thrice weekly before
      dialysis. Predialysis plasma total homocysteine concentrations at weeks 4 and 8
      were compared between groups by paired t test. RESULTS: Mean total homocysteine
      at 8 wk in the placebo group was 24.9 micromol/L compared with 24.3 micromol/L in
      the mesna group (n = 22 [11 pairs]; mean difference 0.63). Interim analysis at 4
      wk also showed no significant difference between mesna and placebo (n = 32 [16
      pairs]; placebo 26.3 micromol/L, mesna 24.5 micromol/L; mean difference 1.88).
      Multivariable adjustments for baseline characteristics did not alter the
      analysis. Plasma mesna seemed to reach steady-state concentrations by 4 wk.
      CONCLUSIONS: It is concluded that 5 mg/kg mesna does not lower plasma total
      homocysteine in hemodialysis patients and that larger dosages may be required.

PMID- 18337552
TI  - Combined effect of chronic kidney disease and peripheral arterial disease on all
      cause mortality in a high-risk population.
AB  - BACKGROUND AND OBJECTIVES: Chronic kidney disease (estimated glomerular
      filtration rate <60 ml/min per 1.73 m(2)) and peripheral arterial disease (ankle
      brachial index <0.9) independently predict mortality. It was hypothesized that
      the risk for death is higher in patients with both chronic kidney disease and
      peripheral arterial disease compared with those with chronic kidney disease or
      peripheral arterial disease alone. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      A total of 1079 patients who had an ankle-brachial index and serum creatinine
      recorded within 90 d of each other in 1999 were studied retrospectively.
      Glomerular filtration rate was estimated using the Modification of Diet in Renal
      Disease equation. Patients were categorized into four groups: Chronic kidney
      disease and peripheral arterial disease, chronic kidney disease alone, peripheral
      arterial disease alone, or no chronic kidney disease or peripheral arterial
      disease. RESULTS: The overall 6-yr mortality rate was 28% (n = 284). Patients
      with both chronic kidney disease and peripheral arterial disease had the highest
      mortality rate (45%) compared with patients with chronic kidney disease alone
      (28%), peripheral arterial disease alone (26%), and neither condition (18%).
      After adjustment for clinical and demographic variables, the chronic kidney
      disease and peripheral arterial disease group had an increased odds for death
      when compared with the no chronic kidney disease or peripheral arterial disease
      group or the single disease groups. CONCLUSIONS: These findings indicate that
      patients with both chronic kidney disease and peripheral arterial disease have a
      significantly higher risk for death than patients with either disease alone.

PMID- 18337553
TI  - History-adjusted marginal structural analysis of the association between
      hemoglobin variability and mortality among chronic hemodialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Hemoglobin variability is common among dialysis
      patients, and has been associated with increased mortality. The causal nature of
      this association has been difficult to ascertain because of potential time
      dependent confounding, for which traditional statistical methods do not control.
      DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: A retrospective cohort of 34,963
      Fresenius Medical care dialysis patients from 1996 was assembled. Hemoglobin
      variability, absolute hemoglobin level, and temporal hemoglobin trend were
      measured over rolling 6-mo exposure windows. Their association with mortality was
      estimated using history-adjusted marginal structural analysis that adjusts for
      time-dependent confounding by applying weights to observations inversely related
      to the predictability of observed levels of hemoglobin. RESULTS: In the primary
      analysis, each g/dl increase in hemoglobin variability was associated with an
      adjusted hazard ratio (HR) [95% confidence interval (CI)] for all-cause mortality
      of 1.93 (1.20 to 3.10). Neither higher absolute hemoglobin level nor increasing
      hemoglobin trend were significantly associated with mortality; adjusted HR (95%
      CI) 0.85 (0.64 to 1.11) and 0.60 (0.25 to 1.45), respectively. CONCLUSIONS:
      Marginal structural analysis demonstrates that hemoglobin variability is
      associated with increased mortality among chronic hemodialysis patients, and that
      this effect is more pronounced than appreciated using standard statistical
      techniques that do not take time-dependent confounding into account.

PMID- 18337554
TI  - Urine NGAL predicts severity of acute kidney injury after cardiac surgery: a
      prospective study.
AB  - BACKGROUND AND OBJECTIVES: The authors have previously shown that urine
      neutrophil gelatinase-associated lipocalin (NGAL), measured by a research ELISA,
      is an early predictive biomarker of acute kidney injury (AKI) after
      cardiopulmonary bypass (CPB). In this study, whether an NGAL immunoassay
      developed for a standardized clinical platform (ARCHITECT analyzer, Abbott
      Diagnostics Division, Abbott Laboratories, Abbott Park, IL) can predict AKI after
      CPB was tested. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a pilot study
      with 136 urine samples (NGAL range, 0.3 to 815 ng/ml) and 6 calibration standards
      (NGAL range, 0 to 1000 ng/ml), NGAL measurements by research ELISA and by the
      ARCHITECT assay were highly correlated (r = 0.99). In a subsequent study, 196
      children undergoing CPB were prospectively enrolled and serial urine NGAL
      measurements obtained by ARCHITECT assay. The primary outcome was AKI, defined as
      a > or = 50% increase in serum creatinine. RESULTS: AKI developed in 99 patients
      (51%), but the diagnosis using serum creatinine was delayed by 2 to 3 d after
      CPB. In contrast, mean urine NGAL levels increased 15-fold within 2 h and by 25
      fold at 4 and 6 h after CPB. For the 2-h urine NGAL measurement, the area under
      the curve was 0.95, sensitivity was 0.82, and the specificity was 0.90 for
      prediction of AKI using a cutoff value of 100 ng/ml. The 2-h urine NGAL levels
      correlated with severity and duration of AKI, length of stay, dialysis
      requirement, and death. CONCLUSIONS: Accurate measurements of urine NGAL are
      obtained using the ARCHITECT platform. Urine NGAL is an early predictive
      biomarker of AKI severity after CPB.

PMID- 18337555
TI  - Association between the proliferative rate of neoplastic B cells, their
      maturation stage, and underlying cytogenetic abnormalities in B-cell chronic
      lymphoproliferative disorders: analysis of a series of 432 patients.
AB  - Limited knowledge exists about the impact of specific genetic abnormalities on
      the proliferation of neoplastic B cells from chronic lymphoproliferative
      disorders (B-CLPDs). Here we analyze the impact of cytogenetic abnormalities on
      the proliferation of neoplastic B cells in 432 B-CLPD patients, grouped according
      to diagnosis and site of sampling, versus their normal counterparts. Overall,
      proliferation of neoplastic B cells highly varied among the different B-CLPD
      subtypes, the greatest numbers of proliferating cells being identified in diffuse
      large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL). Compared with normal B
      cells, neoplastic B-CLPD cells showed significantly increased S + G(2)/M-phase
      values in mantle cell lymphoma (MCL), B-chronic lymphocytic leukemia (B-CLL), BL,
      and some DLBCL cases. Conversely, decreased proliferation was observed in
      follicular lymphoma, lymphoplasmacytic lymphoma/Waldenstrom macroglobulinemia
      (LPL/WM), and some DLBCL patients; hairy cell leukemia, splenic marginal zone,
      and MALT-lymphoma patients showed S + G(2)/M phase values similar to normal
      mature B lymphocytes from LN. Interestingly, in B-CLL and MCL significantly
      higher percentages of S + G(2)/M cells were detected in BM versus PB and in LN
      versus BM and PB samples, respectively. In turn, presence of 14q32.3 gene
      rearrangements and DNA aneuploidy, was associated with a higher percentage of S +
      G(2)/M-phase cells among LPL/WM and B-CLL cases, respectively.

PMID- 18337556
TI  - Nuclear translocation of urokinase-type plasminogen activator.
AB  - Urokinase-type plasminogen activator (uPA) participates in diverse
      (patho)physiological processes through intracellular signaling events that affect
      cell adhesion, migration, and proliferation, although the mechanisms by which
      these occur are only partially understood. Here we report that upon cell binding
      and internalization, single-chain uPA (scuPA) translocates to the nucleus within
      minutes. Nuclear translocation does not involve proteolytic activation or
      degradation of scuPA. Neither the urokinase receptor (uPAR) nor the low-density
      lipoprotein-related receptor (LRP) is required for nuclear targeting. Rather,
      translocation involves the binding of scuPA to the nucleocytoplasmic shuttle
      protein nucleolin through a region containing the kringle domain. RNA
      interference and mutational analysis demonstrate that nucleolin is required for
      the nuclear transport of scuPA. Furthermore, nucleolin is required for the
      induction smooth muscle alpha-actin (alpha-SMA) by scuPA. These data reveal a
      novel pathway by which uPA is rapidly translocated to the nucleus where it might
      participate in regulating gene expression.

PMID- 18337557
TI  - MicroRNA expression profiling in relation to the genetic heterogeneity of acute
      myeloid leukemia.
AB  - Acute myeloid leukemia (AML) is a highly diverse disease characterized by various
      cytogenetic and molecular abnormalities. MicroRNAs are small noncoding RNAs that
      show variable expression during myeloid differentiation. MicroRNA expression in
      marrow blasts in 215 cases of newly diagnosed and (cyto)genetically defined AML
      was assessed using quantitative reverse-transcription-polymerase chain reaction
      (RT-PCR) for 260 human microRNAs. In the same series, mRNA gene expression
      profiles were established, allowing a direct comparison between microRNA and mRNA
      expression. We show that microRNA expression profiling following unsupervised
      analysis reveals distinctive microRNA signatures that correlate with cytogenetic
      and molecular subtypes of AML (ie, AMLs with t(8;21), t(15;17), inv(16), NPM1,
      and CEBPA mutations). Significantly differentially expressed microRNAs for
      genetic subtypes of AML were identified. Specific microRNAs with established
      oncogenic and tumor suppressor functions, such as microRNA-155, microRNA-21, and
      let-7, appear to be associated with particular subtypes. Combinations of selected
      sets of microRNAs could predict cytogenetically normal AML with mutations in the
      genes of NPM1 and CEBPA and FLT3-ITD with similar accuracy as mRNA probe set
      combinations defined by gene expression profiling. MicroRNA expression apparently
      bears specific relationships to the heterogeneous pathobiology of AML.
      Distinctive microRNA signatures appear of potential value in the clinical
      diagnosis of AML.

PMID- 18337558
TI  - Enhanced NK-cell development and function in BCAP-deficient mice.
AB  - In B lymphocytes, the B-cell adaptor for phosphatidylinositol 3-kinase (BCAP)
      facilitates signaling from the antigen receptor. Mice lacking BCAP have a
      predominantly immature pool of B cells with impaired immune function and
      increased susceptibility to apoptosis. Unexpectedly, we have found that natural
      killer (NK) cells from BCAP-deficient mice are more mature, more long-lived, more
      resistant to apoptosis, and exhibit enhanced functional activity compared with NK
      cells from wild-type mice. Surprisingly, these effects are evident despite a
      severe impairment of the immunoreceptor tyrosine-based activation motif-mediated
      Akt signaling pathway. The seemingly paradoxical phenotype reveals inherent
      differences in the signals controlling the final maturation of B cells and NK
      cells, which depend on positive and negative signals, respectively. Both enhanced
      interferon-gamma responses and augmented maturation of NK cells in BCAP-deficient
      mice are independent of available MHC class I ligands. Our data support a model
      in which blunting of BCAP-mediated activation signaling in developing NK cells
      promotes functionality, terminal maturation, and long-term survival.

PMID- 18337559
TI  - An analysis of the clinical and biologic significance of TP53 loss and the
      identification of potential novel transcriptional targets of TP53 in multiple
      myeloma.
AB  - TP53 is a tumor suppressor gene that functions as transcriptional regulator
      influencing cellular responses to DNA damage. Here we explored the clinical and
      transcriptional effects of TP53 expression in multiple myeloma (MM). We found
      that low expression of TP53, seen in approximately 10% of newly diagnosed
      patients, is highly correlated with TP53 deletion, an inferior clinical outcome,
      and represents an independent risk factor. Analysis of the expression of 122
      known TP53 target genes in TP53-high vs -low MM cells from 351 newly diagnosed
      cases, revealed that only a few were highly correlated with TP53 expression. To
      elucidate TP53 regulatory networks in MM, we overexpressed TP53 in 4 MM cell
      lines. Gene expression profiling of these cell lines detected 85 significantly
      differentially expressed genes, with 50 up-regulated and 35 down-regulated.
      Unsupervised hierarchical clustering of myeloma samples from 351 newly diagnosed
      and 90 relapsed patients using the 85 putative TP53 target genes revealed 2 major
      subgroups showing a strong correlation with TP53 expression and survival. These
      data suggest that loss of TP53 expression in MM confers high risk and probably
      results in the deregulation of a novel set of MM-specific TP53-target genes. TP53
      target gene specificity may be unique to different cell lineages.

PMID- 18337560
TI  - IgG regulates the CD1 expression profile and lipid antigen-presenting function in
      human dendritic cells via FcgammaRIIa.
AB  - Dendritic cells (DCs) process and present bacterial and endogenous lipid antigens
      in complex with CD1 molecules to T cells and invariant natural killer T (NKT)
      cells. However, different types of DCs, such as blood myeloid DCs and skin
      Langerhans cells, exhibit distinct patterns of CD1a, CD1b, CD1c, and CD1d
      expression. The regulation of such differences is incompletely understood. Here,
      we initially observed that monocyte-derived DCs cultured in an immunoglobulin
      rich milieu expressed CD1d but not CD1a, CD1b, and CD1c, whereas DCs cultured in
      the presence of low levels of immunoglobulins had an opposite CD1 profile. Based
      on this, we tested the possibility that immunoglobulins play a central role in
      determining these differences. IgG depletion and intravenous immunoglobulin
      (IVIg) add-in experiments strongly supported a role for IgG in directing the CD1
      expression profile. Blocking experiments indicated that this effect was mediated
      by FcgammaRIIa (CD32a), and quantitative polymerase chain reaction data
      demonstrated that regulation of the CD1 profile occurred at the gene expression
      level. Finally, the ability of DCs to activate CD1-restricted NKT cells and T
      cells was determined by this regulatory effect of IgG. Our data demonstrate an
      important role for FcgammaRIIa in regulating the CD1 antigen presentation
      machinery of human DCs.

PMID- 18337561
TI  - Novel HAX1 mutations in patients with severe congenital neutropenia reveal
      isoform-dependent genotype-phenotype associations.
AB  - Homozygous mutations in HAX1 cause an autosomal recessive form of severe
      congenital neutropenia (CN). By screening 88 patients with CN, we identified 6
      additional patients with HAX1 mutations carrying 4 novel mutations. Of these, 2
      affect both published transcript variants of HAX1; the other 2 mutations affect
      only transcript variant 1. Analysis of the patients' genotypes and phenotypes
      revealed a striking correlation: Mutations affecting transcript variant 1 only
      were associated with CN (23 of 23 patients), whereas mutations affecting both
      transcript variants caused CN and neurologic symptoms, including epilepsy and
      neurodevelopmental delay (6 of 6 patients). In contrast to peripheral blood,
      transcript variant 2 was markedly expressed in human brain tissue. The clinical
      phenotype of HAX1 deficiency appears to depend on the localization of the
      mutation and their influence on the transcript variants. Therefore, our findings
      suggest that HAX1 isoforms may play a distinctive role in the neuronal system.

PMID- 18337562
TI  - CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation
      through mTOR/4E-BP1.
AB  - The multistep, coordinated process of T-cell chemotaxis requires chemokines, and
      their chemokine receptors, to invoke signaling events to direct cell migration.
      Here, we examined the role for CCL5-mediated initiation of mRNA translation in
      CD4(+) T-cell chemotaxis. Using rapamycin, an inhibitor of mTOR, our data show
      the importance of mTOR in CCL5-mediated T-cell migration. Cycloheximide, but not
      actinomycin D, significantly reduced chemotaxis, suggesting a possible role for
      mRNA translation in T-cell migration. CCL5 induced phosphorylation/activation of
      mTOR, p70 S6K1, and ribosomal protein S6. In addition, CCL5 induced PI-3'K-,
      phospholipase D (PLD)-, and mTOR-dependent phosphorylation and deactivation of
      the transcriptional repressor 4E-BP1, which resulted in its dissociation from the
      eukaryotic initiation factor-4E (eIF4E). Subsequently, eIF4E associated with
      scaffold protein eIF4G, forming the eIF4F translation initiation complex. Indeed,
      CCL5 initiated active translation of mRNA, shown by the increased presence of
      high-molecular-weight polysomes that were significantly reduced by rapamycin
      treatment. Notably, CCL5 induced protein translation of cyclin D1 and MMP-9,
      known mediators of migration. Taken together, we describe a novel mechanism by
      which CCL5 influences translation of rapamycin-sensitive mRNAs and "primes"
      CD4(+) T cells for efficient chemotaxis.

PMID- 18337563
TI  - TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell
      phenotype.
AB  - Pathological angiogenesis associated with wound healing often occurs subsequent
      to an inflammatory response that includes the secretion of cytokines such as
      tumor necrosis factor (TNF). Controversy exists on the angiogenic actions of TNF,
      with it being generally proangiogenic in vivo, but antiangiogenic in vitro. We
      find that whereas continuous administration of TNF in vitro or in vivo inhibits
      angiogenic sprouting, a 2- to 3-day pulse stimulates angiogenesis by inducing an
      endothelial "tip cell" phenotype. TNF induces the known tip cell genes platelet
      derived growth factor B (PDGFB) and vascular endothelial cell growth factor
      receptor-2 (VEGFR2), while at the same time blocking signaling through VEGFR2,
      thus delaying the VEGF-driven angiogenic response. Notch signaling regulates tip
      cell function, and we find that TNF also induces the notch ligand jagged-1,
      through an NFkappaB-dependent mechanism. Enrichment of jagged-1 in tip cells was
      confirmed by immunofluorescent staining as well as by laser capture
      microdissection/quantitative reverse-transcription-polymerase chain reaction (qRT
      PCR) of tip cells sprouting in vitro. Thus, in angiogenesis, the temporal
      expression of TNF is critical: it delays angiogenesis initially by blocking
      signaling through VEGFR2, but in addition by inducing a tip cell phenotype
      through an NFkappaB-dependent pathway, it concomitantly primes endothelial cells
      (ECs) for sprouting once the initial inflammatory wave has passed.

PMID- 18337564
TI  - FGF-16 is released from neonatal cardiac myocytes and alters growth-related
      signaling: a possible role in postnatal development.
AB  - FGF-16 has been reported to be preferentially expressed in the adult rat heart.
      We have investigated the expression of FGF-16 in the perinatal and postnatal
      heart and its functional significance in neonatal rat cardiac myocytes. FGF-16
      mRNA accumulation was observed by quantitative RT-PCR between neonatal days 1 and
      7, with this increased expression persisting into adulthood. FGF-2 has been shown
      to increase neonatal rat cardiac myocyte proliferative potential via PKC
      activation. Gene array analysis revealed that FGF-16 inhibited the upregulation
      by FGF-2 of cell cycle promoting genes including cyclin F and Ki67. Furthermore,
      the CDK4/6 inhibitor gene Arf/INK4A was upregulated with the combination of FGF
      16 and FGF-2 but not with either factor on its own. The effect on Ki67 was
      validated by protein immunodetection, which also showed that FGF-16 significantly
      decreased FGF-2-induced Ki67 labeling of cardiac myocytes, although it alone had
      no effect on Ki67 labeling. Inhibition of p38 MAPK potentiated cardiac myocyte
      proliferation induced by FGF-2 but did not alter the inhibitory action of FGF-16.
      Receptor binding assay showed that FGF-16 can compete with FGF-2 for binding
      sites including FGF receptor 1. FGF-16 had no effect on activated p38, ERK1/2, or
      JNK/SAPK after FGF-2 treatment. However, FGF-16 inhibited PKC-alpha and PKC
      epsilon activation induced by FGF-2 and, importantly, IGF-1. Collectively, these
      data suggest that expression and release of FGF-16 in the neonatal myocardium
      interfere with cardiac myocyte proliferative potential by altering the local
      signaling environment via modulation of PKC activation and cell cycle-related
      gene expression.

PMID- 18337566
TI  - Transcriptome analysis of infection of the archaeon Sulfolobus solfataricus with
      Sulfolobus turreted icosahedral virus.
AB  - Microarray analysis of infection by Sulfolobus turreted icosahedral virus (STIV)
      revealed insights into the timing and extent of virus transcription, as well as
      differential regulation of host genes. Using a microarray containing genes from
      both the host and the virus, the infection cycle of STIV was studied. Following
      infection of Sulfolobus solfataricus strain 2-2-12 with STIV, transcription of
      virus genes was first detected at 8 h postinfection (p.i.), with a peak at 24 h
      p.i. Lysis of cells was first detected at 32 h p.i. There was little temporal
      control of the transcription of virus genes, although the three open reading
      frames on the noncoding strand were transcribed later in the infection process.
      During the infection, 177 host genes were determined to be differentially
      expressed, with 124 genes up-regulated and 53 genes down-regulated. The up
      regulated genes were dominated by genes associated with DNA replication and
      repair and those of unknown function, while the down-regulated genes, mostly
      detected at 32 h p.i., were associated with energy production and metabolism.
      Examination of infected cells by transmission electron microscopy revealed
      alterations in cell ultrastructure consistent with the microarray analysis. The
      observed patterns of transcription suggest that up-regulated genes are likely
      used by the virus to reprogram the cell for virus replication, while the down
      regulated genes reflect the imminent lysis of the cells.

PMID- 18337567
TI  - Systemic and brain macrophage infections in relation to the development of simian
      immunodeficiency virus encephalitis.
AB  - The brains of individuals with lentiviral-associated encephalitis contain an
      abundance of infected and activated macrophages. It has been hypothesized that
      encephalitis develops when increased numbers of infected monocytes traffic into
      the central nervous system (CNS) during the end stages of immunosuppression. The
      relationships between the infection of brain and systemic macrophages and
      circulating monocytes and the development of lentiviral encephalitis are unknown.
      We longitudinally examined the extent of monocyte/macrophage infection in blood
      and lymph nodes of pigtailed macaques that did or did not develop simian
      immunodeficiency virus encephalitis (SIVE). Compared to levels in macaques that
      did not develop SIVE, more ex vivo virus production was detected from monocyte
      derived macrophages and nonadherent peripheral blood mononuclear cells (PBMCs)
      from macaques that did develop SIVE. Prior to death, there was an increase in the
      number of circulating PBMCs following a rise in cerebrospinal fluid viral load in
      macaques that did develop SIVE but not in nonencephalitic macaques. At necropsy,
      macaques with SIVE had more infected macrophages in peripheral organs, with the
      exception of lymph nodes. T cells and NK cells with cytotoxic potential were more
      abundant in brains with encephalitis; however, T-cell and NK-cell infiltration in
      SIVE and human immunodeficiency virus encephalitis was more modest than that
      observed in classical acute herpes simplex virus encephalitis. These findings
      support the hypothesis that inherent differences in host systemic and CNS
      monocyte/macrophage viral production are associated with the development of
      encephalitis.

PMID- 18337568
TI  - Identification and in vitro expansion of functional antigen-specific CD25+ FoxP3+
      regulatory T cells in hepatitis C virus infection.
AB  - CD4(+)CD25(+) regulatory T cells (CD25(+) Tregs) play a key role in immune
      regulation. Since hepatitis C virus (HCV) persists with increased circulating
      CD4(+)CD25(+) T cells and virus-specific effector T-cell dysfunction, we asked if
      CD4(+)CD25(+) T cells in HCV-infected individuals are similar to natural Tregs in
      uninfected individuals and if they include HCV-specific Tregs using the specific
      Treg marker FoxP3 at the single-cell level. We report that HCV-infected patients
      display increased circulating FoxP3(+) Tregs that are phenotypically and
      functionally indistinguishable from FoxP3(+) Tregs in uninfected subjects.
      Furthermore, HCV-specific FoxP3(+) Tregs were detected in HCV-seropositive
      persons with antigen-specific expansion, major histocompatibility complex class
      II/peptide tetramer binding affinity, and preferential suppression of HCV
      specific CD8 T cells. Transforming growth factor beta contributed to antigen
      specific Treg expansion in vitro, suggesting that it may contribute to antigen
      specific Treg expansion in vivo. Interestingly, FoxP3 expression was also
      detected in influenza virus-specific CD4 T cells. In conclusion, functionally
      active and virus-specific FoxP3(+) Tregs are induced in HCV infection, thus
      providing targeted immune regulation in vivo. Detection of FoxP3 expression in
      non-HCV-specific CD4 T cells suggests that immune regulation through antigen
      specific Treg induction extends beyond HCV.

PMID- 18337569
TI  - Histone hyperacetylation occurs on promoters of lytic cycle regulatory genes in
      Epstein-Barr virus-infected cell lines which are refractory to disruption of
      latency by histone deacetylase inhibitors.
AB  - Activation of the Epstein-Barr virus (EBV) lytic cycle is mediated through the
      combined actions of ZEBRA and Rta, the products of the viral BZLF1 and BRLF1
      genes. During latency, these two genes are tightly repressed. Histone deacetylase
      inhibitors (HDACi) can activate viral lytic gene expression. Therefore, a widely
      held hypothesis is that Zp and Rp, the promoters for BZLF1 and BRLF1, are
      repressed by chromatin and that hyperacetylation of histone tails, by allowing
      the access of positively acting factors, leads to transcription of BZLF1 and
      BRLF1. To investigate this hypothesis, we used chromatin immunoprecipitation
      (ChIP) to examine the acetylation and phosphorylation states of histones H3 and
      H4 on Zp and Rp in three cell lines, Raji, B95-8, and HH514-16, which differ in
      their response to EBV lytic induction by HDACi. We studied the effects of three
      HDACi, sodium butyrate (NaB), trichostatin A (TSA), and valproic acid (VPA). We
      also examined the effects of tetradecanoyl phorbol acetate (TPA) and 5-aza-2'
      deoxycytidine, a DNA methyltransferase inhibitor, on histone modification. In
      Raji cells, TPA and NaB act synergistically to activate the EBV lytic cycle and
      promote an increase in histone H3 and H4 acetylation and phosphorylation at Zp
      and Rp. Surprisingly, however, when Raji cells were treated with NaB or TSA,
      neither of which is sufficient to activate the lytic cycle, an increase of
      comparable magnitude of hyperacetylated and phosphorylated histone H3 at Zp and
      Rp was observed. In B95-8 cells, NaB inhibited lytic induction by TPA, yet NaB
      promoted hyperacetylation of H3 and H4. In HH514-16 cells, NaB and TSA strongly
      activated the EBV lytic cycle and caused hyperacetylation of histone H3 on Zp and
      Rp. However, when HH514-16 cells were treated with VPA, lytic cycle mRNAs or
      proteins were not induced, although histone H3 was hyperacetylated as measured by
      immunoblotting or by ChIP on Zp and Rp. Taken together, our data suggest that
      open chromatin at EBV BZLF1 and BRLF1 promoters is not sufficient to activate EBV
      lytic cycle gene expression.

PMID- 18337570
TI  - CD81 and claudin 1 coreceptor association: role in hepatitis C virus entry.
AB  - Hepatitis C virus (HCV) is an enveloped positive-stranded RNA hepatotropic virus.
      HCV pseudoparticles infect liver-derived cells, supporting a model in which liver
      specific molecules define HCV internalization. Three host cell molecules have
      been reported to be important entry factors or receptors for HCV internalization:
      scavenger receptor BI, the tetraspanin CD81, and the tight junction protein
      claudin-1 (CLDN1). None of the receptors are uniquely expressed within the liver,
      leading us to hypothesize that their organization within hepatocytes may explain
      receptor activity. Since CD81 and CLDN1 act as coreceptors during late stages in
      the entry process, we investigated their association in a variety of cell lines
      and human liver tissue. Imaging techniques that take advantage of fluorescence
      resonance energy transfer (FRET) to study protein-protein interactions have been
      developed. Aequorea coerulescens green fluorescent protein- and Discosoma sp. red
      monomer fluorescent protein-tagged forms of CD81 and CLDN1 colocalized, and FRET
      occurred between the tagged coreceptors at comparable frequencies in permissive
      and nonpermissive cells, consistent with the formation of coreceptor complexes.
      FRET occurred between antibodies specific for CD81 and CLDN1 bound to human liver
      tissue, suggesting the presence of coreceptor complexes in liver tissue. HCV
      infection and treatment of Huh-7.5 cells with recombinant HCV E1-E2 glycoproteins
      and anti-CD81 monoclonal antibody modulated homotypic (CD81-CD81) and heterotypic
      (CD81-CLDN1) coreceptor protein association(s) at specific cellular locations,
      suggesting distinct roles in the viral entry process.

PMID- 18337571
TI  - Human herpesvirus 8 infects and replicates in primary cultures of activated B
      lymphocytes through DC-SIGN.
AB  - Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma, primary
      effusion lymphoma, and some forms of multicentric Castleman's disease. Although
      latent HHV-8 DNA can be detected in B cells from persons with these cancers,
      there is little information on the replication of HHV-8 in B cells. Indeed, B
      cells are relatively resistant to HHV-8 infection in vitro. We have recently
      shown that DC-SIGN, a C-type lectin first identified on dendritic cells (DC), is
      an entry receptor for HHV-8 on DC and macrophages. We have also demonstrated
      previously that B lymphocytes from peripheral blood and tonsils express DC-SIGN
      and that this expression increases after B-cell activation. Here we show that
      activated blood and tonsillar B cells can be productively infected with HHV-8, as
      measured by an increase in viral DNA, the expression of viral lytic and latency
      proteins, and the production of infectious virus. The infection of B cells with
      HHV-8 was blocked by the pretreatment of the cells with antibody specific for DC
      SIGN or with mannan but not antibody specific for xCT, a cystine/glutamate
      exchange transporter that has been implicated in HHV-8 fusion to cells. The
      infection of B cells with HHV-8 resulted in increased expression of DC-SIGN and a
      decrease in the expression of CD20 and major histocompatibility complex class I.
      HHV-8 could also infect and replicate in B-cell lines transduced to express full
      length DC-SIGN but not in B-cell lines transduced to express DC-SIGN lacking the
      transmembrane domain, demonstrating that the entry of HHV-8 into B cells is
      related to DC-SIGN-mediated endocytosis. The role of endocytosis in viral entry
      into activated B cells was confirmed by blocking HHV-8 infection with endocytic
      pathway inhibitors. Thus, the expression of DC-SIGN is essential for productive
      HHV-8 infection of and replication in B cells.

PMID- 18337572
TI  - Transmission of simian immunodeficiency virus carrying multiple cytotoxic T
      lymphocyte escape mutations with diminished replicative ability can result in
      AIDS progression in rhesus macaques.
AB  - Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency
      virus mutations that result in escape from CTL recognition with viral fitness
      costs. The replication in vivo of such viruses carrying not single but multiple
      escape mutations in the absence of the CTL pressure has remained undetermined.
      Here, we have examined the replication of simian immunodeficiency virus (SIV)
      with five gag mutations selected in a macaque possessing the major
      histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120
      Ia-negative macaques. Our results showed that even such a "crippled" SIV
      infection can result in persistent viral replication, multiple reversions, and
      AIDS progression.

PMID- 18337573
TI  - Dimerization of the human papillomavirus type 16 E2 N terminus results in DNA
      looping within the upstream regulatory region.
AB  - Papillomavirus E2 proteins play a central role in regulating viral gene
      expression and replication. DNA-binding activity is associated with the C
      terminal domain of E2, which forms a stable dimer, while the N-terminal domain is
      responsible for E2's replication and transactivation functions. The crystal
      structure of the latter domain revealed a second dimerization interface on E2
      which may be responsible for DNA loop formation in the regulatory region of the
      human papillomavirus (HPV) genome. We investigated the biological significance of
      the N-terminal dimerization by introducing single amino acid substitutions into
      the dimerization interface. As expected, these substitutions did not influence
      the C-terminal dimerization and DNA-binding functions of E2. However, the
      mutations led to reduced transactivation of a synthetic E2-responsive reporter
      gene, while HPV DNA replication was unaffected. The effect of the mutations on
      DNA looping was visualized by atomic force microscopy. While wild-type E2 was
      able to generate DNA loops, all three mutant E2 proteins were defective in this
      ability. Our results suggest that N-terminal dimerization plays a role in E2
      mediated transactivation, probably via DNA looping, a common mechanism for remote
      regulation of gene transcription.

PMID- 18337574
TI  - The early kinetics of cytomegalovirus-specific CD8+ T-cell responses are not
      affected by antigen load or the absence of perforin or gamma interferon.
AB  - Both innate and adaptive immune responses participate in the control of murine
      cytomegalovirus (mCMV) infection. In some mouse strains, like BALB/c, the control
      of infection relies on the activities of CD8(+) T cells. mCMV-specific CD8(+) T
      cell responses are unusual in that, even after mCMV has been controlled in the
      periphery, the numbers of circulating virus-specific CD8(+) T cells remain high
      compared to those observed in other viral infections. To better understand the
      generation and maintenance of mCMV-specific CD8(+) T-cell responses, we evaluated
      how antigen load and effector molecules, such as perforin (Prf) and gamma
      interferon (IFN-gamma), influence these responses during acute infection in vivo.
      Viral burden affected the magnitude, but not the early kinetics, of antigen
      specific CD8(+) T-cell responses. Similarly, the magnitude of virus-specific
      CD8(+) T-cell expansion was affected by Prf and IFN-gamma, but contraction of
      antigen-specific responses occurred normally in both Prf- and IFN-gamma-deficient
      mice. These data indicate that control of mCMV-specific CD8(+) T-cell expansion
      and contraction is more complex than anticipated and, despite the role of Prf or
      IFN-gamma in controlling viral replication, a full program of T-cell expansion
      and contraction can occur in their absence.

PMID- 18337575
TI  - Magnitude and phenotype of cellular immune responses elicited by recombinant
      adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys.
AB  - Recombinant adenovirus serotype 5 (rAd5) vaccine vectors for human
      immunodeficiency virus type 1 (HIV-1) and other pathogens have been shown to
      elicit antigen-specific cellular immune responses. Rare serotype rAd vectors have
      also been constructed to circumvent preexisting anti-Ad5 immunity and to
      facilitate the development of novel heterologous rAd prime-boost regimens. Here
      we show that rAd5, rAd26, and rAd48 vectors elicit qualitatively distinct
      phenotypes of cellular immune responses in rhesus monkeys and can be combined as
      potent heterologous prime-boost vaccine regimens. While rAd5-Gag induced
      primarily gamma interferon-positive (IFN-gamma(+)) and IFN-gamma(+)/tumor
      necrosis factor alpha(+) (TNF-alpha(+)) T-lymphocyte responses, rAd26-Gag and
      rAd48-Gag induced higher proportions of interleukin-2(+) (IL-2(+)) and
      polyfunctional IFN-gamma(+)/TNF-alpha(+)/IL-2(+) T-lymphocyte responses. Priming
      with the rare serotype rAd vectors proved remarkably effective for subsequent
      boosting with rAd5 vectors. These data demonstrate that the rare serotype rAd
      vectors elicited T-lymphocyte responses that were phenotypically distinct from
      those elicited by rAd5 vectors and suggest the functional relevance of
      polyfunctional CD8(+) and CD4(+) T-lymphocyte responses. Moreover, qualitative
      differences in cellular immune responses may prove critical in determining the
      overall potency of heterologous rAd prime-boost regimens.

PMID- 18337576
TI  - Variable patterns of programmed death-1 expression on fully functional memory T
      cells after spontaneous resolution of hepatitis C virus infection.
AB  - The inhibitory receptor programmed death-1 (PD-1) is present on CD8(+) T cells in
      chronic hepatitis C virus (HCV), but expression patterns in spontaneously
      resolving infections are incompletely characterized. Here we report that PD-1 was
      usually absent on memory CD8(+) T cells from chimpanzees with resolved
      infections, but sustained low-level expression was sometimes observed in the
      absence of apparent virus replication. PD-1-positive memory T cells expanded and
      displayed antiviral activity upon reinfection with HCV, indicating conserved
      function. This animal model should facilitate studies of whether PD-1
      differentially influences effector and memory T-cell function in resolved versus
      persistent human infections.

PMID- 18337577
TI  - Live visualization of herpes simplex virus type 1 compartment dynamics.
AB  - We have constructed a recombinant herpes simplex virus type 1 (HSV-1) that
      simultaneously encodes selected structural proteins from all three virion
      compartments-capsid, tegument, and envelope-fused with autofluorescent proteins.
      This triple-fluorescent recombinant, rHSV-RYC, was replication competent, albeit
      with delayed kinetics, incorporated the fusion proteins into all three virion
      compartments, and was comparable to wild-type HSV-1 at the ultrastructural level.
      The VP26 capsid fusion protein (monomeric red fluorescent protein [mRFP]-VP26)
      was first observed throughout the nucleus and later accumulated in viral
      replication compartments. In the course of infection, mRFP-VP26 formed small foci
      in the periphery of the replication compartments that expanded and coalesced over
      time into much larger foci. The envelope glycoprotein H (gH) fusion protein
      (enhanced yellow fluorescent protein [EYFP]-gH) was first observed accumulating
      in a vesicular pattern in the cytoplasm and was then incorporated primarily into
      the nuclear membrane. The VP16 tegument fusion protein (VP16-enhanced cyan
      fluorescent protein [ECFP]) was first observed in a diffuse nuclear pattern and
      then accumulated in viral replication compartments. In addition, it also formed
      small foci in the periphery of the replication compartments which, however, did
      not colocalize with the small mRFP-VP26 foci. Later, VP16-ECFP was redistributed
      out of the nucleus into the cytoplasm, where it accumulated in vesicular foci and
      in perinuclear clusters reminiscent of the Golgi apparatus. Late in infection,
      mRFP-VP26, EYFP-gH, and VP16-ECFP were found colocalizing in dots at the plasma
      membrane, possibly representing mature progeny virus. In summary, this study
      provides new insights into the dynamics of compartmentalization and interaction
      among capsid, tegument, and envelope proteins. Similar strategies can also be
      applied to assess other dynamic events in the virus life cycle, such as entry and
      trafficking.

PMID- 18337578
TI  - The thiazolobenzimidazole TBZE-029 inhibits enterovirus replication by targeting
      a short region immediately downstream from motif C in the nonstructural protein
      2C.
AB  - TBZE-029 {1-(2,6-difluorophenyl)-6-trifluoromethyl-1H,3H-thiazolo[3,4
      a]benzimidazole} is a novel selective inhibitor of the replication of several
      enteroviruses. We show that TBZE-029 exerts its antiviral activity through
      inhibition of viral RNA replication, without affecting polyprotein processing. To
      identify the viral target of TBZE-029, drug-resistant coxsackievirus B3 (CVB3)
      was selected. Genotyping of resistant clones led to the identification of three
      amino acid mutations in nonstructural protein 2C, clustered at amino acid
      positions 224, 227, and 229, immediately downstream of NTPase/helicase motif C.
      The mutations were reintroduced, either alone or combined, into an infectious
      full-length CVB3 clone. In particular the mutations at positions 227 and 229
      proved essential for the altered sensitivity of CVB3 to TBZE-029. Resistant virus
      exhibited cross-resistance to the earlier-reported antienterovirus agents
      targeting 2C, namely, guanidine hydrochloride, HBB [2-(alpha-hydroxybenzyl)
      benzimidazole], and MRL-1237 {1-(4-fluorophenyl)-2-[(4-imino-1,4-dihydropyridin-1
      yl)methyl]benzimidazole hydrochloride}. The ATPase activity of 2C, however,
      remained unaltered in the presence of TBZE-029.

PMID- 18337579
TI  - Domain within herpes simplex virus 1 scaffold proteins required for interaction
      with portal protein in infected cells and incorporation of the portal vertex into
      capsids.
AB  - The portal vertex of herpesvirus capsids serves as the conduit through which DNA
      is inserted during the assembly process. In herpes simplex virus (HSV), the
      portal is composed of 12 copies of the U(L)6 gene product, pU(L)6. Previous
      results identified a domain in the major capsid scaffold protein, ICP35, required
      for interaction with pU(L)6 and its incorporation into capsids formed in vitro
      (G. P. Singer et al., J. Virol. 74:6838-6848, 2005). In the current studies,
      pU(L)6 and scaffold proteins were found to coimmunoprecipitate from lysates of
      both HSV-infected cells and mammalian cells expressing scaffold proteins and
      pU(L)6. The coimmunoprecipitation of pU(L)6 and scaffold proteins was precluded
      upon deletion of codons 143 to 151 within U(L)26.5, encoding ICP35. While wild
      type scaffold proteins colocalized with pU(L)6 when transiently coexpressed as
      viewed by indirect immunofluorescence, deletion of U(L)26.5 codons 143 to 151
      precluded this colocalization. A recombinant herpes simplex virus, vJB11, was
      generated that lacked U(L)26.5 codons 143 to 151. A virus derived from this
      mutant but bearing a restored U(L)26.5 was also generated. vJB11 was unable to
      cleave or package viral DNA, whereas the restored virus packaged DNA normally.
      vJB11 produced ample numbers of B capsids in infected cells, but these lacked
      normal levels of pU(L)6. The deletion in U(L)26.5 also rendered pU(L)6 resistant
      to detergent extraction from vJB11-infected cells. These data indicate that, as
      was observed in vitro, amino acids 143 to 151 of ICP35 are critical for (i)
      interaction between scaffold proteins and pU(L)6 and (ii) incorporation of the
      HSV portal into capsids.

PMID- 18337580
TI  - Cloning of the koi herpesvirus genome as an infectious bacterial artificial
      chromosome demonstrates that disruption of the thymidine kinase locus induces
      partial attenuation in Cyprinus carpio koi.
AB  - Koi herpesvirus (KHV) is the causative agent of a lethal disease in koi and
      common carp. In the present study, we describe the cloning of the KHV genome as a
      stable and infectious bacterial artificial chromosome (BAC) clone that can be
      used to produce KHV recombinant strains. This goal was achieved by the insertion
      of a loxP-flanked BAC cassette into the thymidine kinase (TK) locus. This
      insertion led to a BAC plasmid that was stably maintained in bacteria and was
      able to regenerate virions when permissive cells were transfected with the
      plasmid. Reconstituted virions free of the BAC cassette but carrying a disrupted
      TK locus (the FL BAC-excised strain) were produced by the transfection of Cre
      recombinase-expressing cells with the BAC. Similarly, virions with a wild-type
      revertant TK sequence (the FL BAC revertant strain) were produced by the
      cotransfection of cells with the BAC and a DNA fragment encoding the wild-type TK
      sequence. Reconstituted recombinant viruses were compared to the wild-type
      parental virus in vitro and in vivo. The FL BAC revertant strain and the FL BAC
      excised strain replicated comparably to the parental FL strain. The FL BAC
      revertant strain induced KHV infection in koi carp that was indistinguishable
      from that induced by the parental strain, while the FL BAC-excised strain
      exhibited a partially attenuated phenotype. Finally, the usefulness of the KHV
      BAC for recombination studies was demonstrated by the production of an ORF16
      deleted strain by using prokaryotic recombination technology. The availability of
      the KHV BAC is an important advance that will allow the study of viral genes
      involved in KHV pathogenesis, as well as the production of attenuated recombinant
      candidate vaccines.

PMID- 18337581
TI  - Generation of antiviral major histocompatibility complex class I-restricted T
      cells in the absence of CD8 coreceptors.
AB  - The CD8 coreceptor is important for positive selection of major
      histocompatibility complex I (MHC-I)-restricted thymocytes and in the generation
      of pathogen-specific T cells. However, the requirement for CD8 in these processes
      may not be essential. We previously showed that mice lacking beta(2)
      microglobulin are highly susceptible to tumors induced by mouse polyoma virus
      (PyV), but CD8-deficient mice are resistant to these tumors. In this study, we
      show that CD8-deficient mice also control persistent PyV infection as efficiently
      as wild-type mice and generate a substantial virus-specific, MHC-I-restricted, T
      cell response. Infection with vesicular stomatitis virus (VSV), which is acutely
      cleared, also recruited antigen-specific, MHC-I-restricted T cells in CD8
      deficient mice. Yet, unlike in VSV infection, the antiviral MHC-I-restricted T
      cell response to PyV has a prolonged expansion phase, indicating a requirement
      for persistent infection in driving T-cell inflation in CD8-deficient mice.
      Finally, we show that the PyV-specific, MHC-I-restricted T cells in CD8-deficient
      mice, while maintained long term at near-wild-type levels, are short lived in
      vivo and have extremely narrow T-cell receptor repertoires. These findings
      provide a possible explanation for the resistance of CD8-deficient mice to PyV
      induced tumors and have implications for the maintenance of virus-specific MHC-I
      restricted T cells during persistent infection.

PMID- 18337582
TI  - Polyomavirus middle T antigen induces the transcription of osteopontin, a gene
      important for the migration of transformed cells.
AB  - Middle T antigen (MT) is the principal oncoprotein of murine polyomavirus.
      Experiments on the acute immediate effects of MT expression on cellular RNA
      levels showed that expression of osteopontin (OPN) was strongly induced by MT
      expression. Osteopontin is a protein known to be associated with cancer. It has a
      role in tumor progression and invasion. Protein analysis confirmed that MT
      induced the secretion of OPN into the extracellular medium. Expression of
      antisense OPN RNA had no effect on the growth of MT-transformed cells. However,
      it had a strong effect on the ability of MT transformants to migrate or to fill a
      wound. Analysis of MT mutants implicated both the SHC and phosphatidylinositol 3
      kinase pathways in OPN induction. Reporter assays showed that MT regulated the
      OPN promoter through two of its PEA3 (polyoma enhancer activator 3) sites. As
      critical PEA3 sites are also part of the polyomavirus enhancer, the same
      signaling important for viral replication also contributes to virally induced
      metastatic potential.

PMID- 18337583
TI  - Role of nonstructural protein NS2A in flavivirus assembly.
AB  - Flavivirus nonstructural (NS) proteins are involved in RNA replication and
      modulation of the host antiviral response; however, evidence is mounting that
      some NS proteins also have essential roles in virus assembly. Kunjin virus (KUN)
      NS2A is a small, hydrophobic, transmembrane protein that is part of the
      replication complex and inhibits interferon induction. Previously, we have shown
      that an isoleucine (I)-to-asparagine (N) substitution at position 59 of the NS2A
      protein blocked the production of secreted virus particles in cells
      electroporated with viral RNA carrying this mutation. We now show that prolonged
      incubation of mutant KUN NS2A-I59N replicon RNA, in an inducible BHK-derived
      packaging cell line (expressing KUN structural proteins C, prM, and E), generated
      escape mutants that rescued the secretion of infectious virus-like particles.
      Sequencing identified three groups of revertants that included (i) reversions to
      wild-type, hydrophobic Ile, (ii) pseudorevertants to more hydrophobic residues
      (Ser, Thr, and Tyr) at codon 59, and (iii) pseudorevertants retaining Asn at NS2A
      codon 59 but containing a compensatory mutation (Thr-to-Pro) at NS2A codon 149.
      Engineering hydrophobic residues at NS2A position 59 or the compensatory T149P
      mutation into NS2A-I59N replicon RNA restored the assembly of secreted virus-like
      particles in packaging cells. T149P mutation also rescued virus production when
      introduced into the full-length KUN RNA containing an NS2A-I59N mutation.
      Immunofluorescence and electron microscopy analyses of NS2A-I59N replicon
      expressing cells showed a distinct lack of virus-induced membranes normally
      present in cells expressing wild-type replicon RNA. The compensatory mutation
      NS2A-T149P restored the induction of membrane structures to a level similar to
      those observed during wild-type replication. The results further confirm the role
      of NS2A in virus assembly, demonstrate the importance of hydrophobic residues at
      codon 59 in this process, implicate the involvement of NS2A in the biogenesis of
      virus-induced membranes, and suggest a vital role for the virus-induced membranes
      in virus assembly.

PMID- 18337584
TI  - Role for the L1-52/55K protein in the serotype specificity of adenovirus DNA
      packaging.
AB  - The packaging of adenovirus (Ad) DNA into virions is dependent upon cis-acting
      sequences and trans-acting proteins. We studied the involvement of Ad packaging
      proteins in the serotype specificity of packaging. Both Ad5 and Ad17 IVa2 and L4
      22K proteins complemented the growth of Ad5 IVa2 and L4-22K mutant viruses,
      respectively. In contrast, the Ad5 L1-52/55K protein complemented an Ad5 L1
      52/55K mutant virus, but the Ad17 L1-52/55K protein did not. The analysis of
      chimeric proteins demonstrated that the N-terminal half of the Ad5 L1-52/55K
      protein mediated this function. Finally, we demonstrate that the L4-33K and L4
      22K proteins have distinct functions during infection.

PMID- 18337585
TI  - Invited article: is it time for neurohospitalists?
AB  - BACKGROUND: Explosive growth of hospital-based medicine specialists, termed
      hospitalists, has occurred in the past decade. This was fueled by pressures
      within the American health care system for timely, cost-effective, and high
      quality care and by the growing chasm between inpatient and outpatient care. In
      this article, we sought to answer five questions: 1) What is a neurohospitalist?
      2) How many neurohospitalists practice in the United States? 3) What are
      potential advantages of neurohospitalists? 4) What are the challenges of
      implementing a neurohospitalist practice? 5) What effect does a neurohospitalist
      have on clinical outcomes? METHODS: We queried biomedical databases (e.g.,
      PubMed) by using the search terms "hospitalist," "neurohospitalist," and
      "neurology hospitalist." We also searched the Society of Hospital Medicine and
      the American Academy of Neurology Dendrite classified advertisement Web sites for
      hospitalist and neurology hospitalist growth by using the same search terms.
      RESULTS: We defined neurology hospitalists (neurohospitalists) as neurologists
      who devote at least one-quarter of their time managing inpatients with neurologic
      disease. Although the number of hospitalists has grown considerably over the past
      decade, limited data on neurohospitalists exist. Advertisements for
      neurohospitalist positions have increased from 2003 through 2007, but accurate
      assessment of growth is limited by the lack of a central organizational
      affiliation and unifying terminology. CONCLUSION: Health care pressures spawned
      the growth of medicine and pediatric hospitalists, who provide efficient, cost
      effective care by reducing the length of hospitalization. Because neurologists
      experience the same pressures, we expect neurohospitalists to increase in number,
      especially within areas that have sufficient inpatient volume and resources.

PMID- 18337586
TI  - Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease.
AB  - OBJECTIVE: Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common
      cause of Parkinson disease (PD). Several dominantly inherited pathogenic
      substitutions have been identified in different domains of the Lrrk2 protein.
      Herein, we characterize the clinical and genetic features associated with Lrrk2
      p.R1441C. METHODS: We identified 33 affected and 15 unaffected LRRK2 c.4321C>T
      (p.R1441C) mutation carriers through an international consortium originating from
      three continents. The age-specific cumulative incidence of PD was calculated by
      Kaplan-Meier analysis. RESULTS: The clinical presentation of Lrrk2 p.R1441C
      carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age
      at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the
      patients had symptoms before the age 50 years, while by 75 years >90% of them had
      developed symptoms. Haplotype analysis suggests four independent founders for the
      p.R1441C mutation. CONCLUSIONS: The distribution in age at onset and clinical
      features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S
      parkinsonism. Several independent founders of the p.R1441C substitution suggest
      this site is prone to recurrent mutagenesis.

PMID- 18337587
TI  - SPG11 mutations are common in familial cases of complicated hereditary spastic
      paraplegia.
AB  - BACKGROUND: Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin
      corpus callosum (TCC) is a common form of complex hereditary spastic paraplegia.
      The genetic lesion underlying ARHSP-TCC was localized to chromosome 15q13-q15 and
      given the designation SPG11. Recently, the gene encoding spatacsin (KIAA1840) has
      been shown to contain mutations that underlie the majority of ARHSP-TCC cases.
      METHODS: We present a complete analysis of the 40 coding exons of this gene in
      patients with sporadic (n = 25) or familial (20 probands) complex hereditary
      spastic paraplegia with and without thinning of the corpus callosum. RESULTS: We
      identified seven mutations, including deletions, insertions, and nonsense
      mutations, which were all predicted to lead to premature truncation of the
      protein. CONCLUSION: We conclude that mutations on KIAA1840 are frequent in
      complex autosomal recessive hereditary spastic paraplegia but an infrequent cause
      of sporadic complex hereditary spastic paraplegia.

PMID- 18337588
TI  - Specific mutations in methyl-CpG-binding protein 2 confer different severity in
      Rett syndrome.
AB  - OBJECTIVE: To determine if a relationship exists between the clinical features of
      Rett syndrome, an X-linked dominant neurodevelopmental disorder, and specific
      mutations in MECP2. METHOD: Cross-sectional study of 245 girls and women with
      typical Rett syndrome seen between 1990 and 2004 in tertiary academic outpatient
      specialty clinics and who had complete MECP2 mutation analysis. A structured
      clinical evaluation was completed for each participant. The results were grouped
      by MECP2 mutation and compared. RESULTS: Participants with the R133C mutation are
      less severely affected than those with R168X or large DNA deletions (p < 0.05).
      Likewise, individuals with the R168X mutation are more severely affected than
      those with R294X and late carboxy-terminal truncating mutations (p < 0.05).
      Clinical differences are notable in ambulation, hand use, and language (p <
      0.004), three cardinal features of Rett syndrome. Individuals with R168X are less
      likely to walk (p = 0.008), retain hand use (p = 0.002), or use words (p =
      0.001). In contrast, those with carboxy-terminal truncations are more likely to
      walk (p = 0.007) and use words (p < 0.001). The R306C mutation, previously found
      to confer milder features, adversely affects only one clinical feature, language
      (p < 0.05). CONCLUSIONS: Specific mutations in MECP2 confer different severity.
      These results allow the design of therapies targeted toward the amelioration of
      expected problems. Furthermore, the distinct effects of MECP2 mutations on
      clinical severity must be considered in clinical intervention trials.

PMID- 18337589
TI  - Cross talk of signaling pathways in the regulation of the glucocorticoid receptor
      function.
AB  - Several posttranslational modifications including phosphorylation have been
      detected on the glucocorticoid receptor (GR). However, the interdependence and
      combinatorial regulation of these modifications and their role in GR functions
      are poorly understood. We studied the effects of c-Jun N-terminal kinase (JNK)
      dependent phosphorylation of GR on its sumoylation status and the impact that
      these modifications have on GR transcriptional activity. GR is targeted for
      phosphorylation at serine 246 (S246) by the JNK protein family in a rapid and
      transient manner. The levels of S246 phosphorylation of endogenous GR increased
      significantly in cells treated with UV radiation that activates JNK. S246 GR
      phosphorylation by JNK facilitated subsequent GR sumoylation at lysines 297 and
      313. GR sumoylation increased with JNK activation and was inhibited in cells
      treated with JNK inhibitor. GR sumoylation in cells with activated JNK was
      mediated preferentially by small ubiquitin-like modifier (SUMO)2 rather than
      SUMO1. An increase in GR transcriptional activity was observed after inhibition
      of JNK or SUMO pathways and suppression of GR transcriptional activity after
      activation of both pathways in cells transfected with GR-responsive reporter
      genes. Endogenous GR transcriptional activity was inhibited on endogenous target
      genes IGF binding protein (IGFBP) and glucocorticoid-induced leucine zipper
      (GILZ) when JNK and SUMO pathways were induced individually or simultaneously.
      Activation of both of these signals inhibited GR-mediated regulation of human
      inhibitor of apoptosis gene (hIAP), whereas simultaneous activation had no
      effect. We conclude that phosphorylation aids GR sumoylation and that cross talk
      of JNK and SUMO pathways fine tune GR transcriptional activity in a target gene
      specific manner, thereby modulating the hormonal response of cells exposed to
      stress.

PMID- 18337590
TI  - Obestatin induction of early-response gene expression in gastrointestinal and
      adipose tissues and the mediatory role of G protein-coupled receptor, GPR39.
AB  - Obestatin was identified as a brain/gut peptide hormone encoded by the ghrelin
      gene and found to interact with the G protein-coupled receptor, GPR39. We
      investigated target cells for obestatin based on induction of an early-response
      gene c-fos in different tissues. After ip injection of obestatin, c-fos staining
      was found in the nuclei of gastric mucosa, intestinal villi, white adipose
      tissues, hepatic cords, and kidney tubules. Immunohistochemical analyses using
      GPR39 antibodies further revealed cytoplasmic staining in these tissues. In
      cultured 3T3-L1 cells, treatment with obestatin, but not motilin, induced c-fos
      expression. In these preadipocytes, treatment with obestatin also stimulated
      ERK1/2 phosphorylation. Because phenotypes of GPR39 null mice are partially
      consistent with a role of GPR39 in mediating obestatin actions, we hypothesized
      that inconsistencies on the binding of iodinated obestatin to GPR39 are due to
      variations in the bioactivity of iodinated obestatin. We obtained
      monoiodoobestatin after HPLC purification and demonstrated its binding to
      jejunum, stomach, ileum, pituitary, and white adipose tissue. Furthermore, human
      embryonic kidney 293T cells transfected with plasmids encoding human or mouse
      GPR39 or a human GPR39 isoform, but not the ghrelin receptor, exhibited high
      affinity binding to monoiodoobestatin. Binding studies using jejunum homogenates
      and recombinant GPR39 revealed obestatin-specific displacement curves.
      Furthermore, treatment with obestatin induced c-fos expression in gastric mucosa
      of wild-type, but not GPR39 null, mice, underscoring a mediating role of this
      receptor in obestatin actions. The present findings indicate that obestatin is a
      metabolic hormone capable of binding to GPR39 to regulate the functions of
      diverse gastrointestinal and adipose tissues.

PMID- 18337591
TI  - Silencing of the mineralocorticoid receptor by ribonucleic acid interference in
      transgenic rats disrupts endocrine homeostasis.
AB  - Currently, gene disruption by homologous recombination in embryonic stem cells is
      only feasible in mice. To circumvent this problem, we silenced mineralocorticoid
      receptor (MR) expression by RNA interference in knockdown rats generated through
      lentiviral transgenesis. Analysis of the F1 progeny at 3 wk of age revealed
      strongly decreased MR levels. This was specific for the targeted gene and related
      to the abundance of the short interfering RNA. Reminiscent of MR knockout mice,
      the transgenic rats showed a reduced body weight, elevated serum aldosterone
      levels, increased plasma renin activity, and altered expression of MR target
      genes. Some of these effects correlated with the degree to which MR mRNA
      expression was reduced. Whereas disruption of the MR by gene targeting in mice
      leads to postnatal death, our strategy also allowed obtaining adult knockdown
      rats with defects in hormone and electrolyte homeostasis resembling
      pseudohypoaldosteronism. In conclusion, this is the first example of a human
      disease model based on RNA interference in rats.

PMID- 18337592
TI  - Effective cellular uptake and efflux of thyroid hormone by human monocarboxylate
      transporter 10.
AB  - Cellular entry of thyroid hormone is mediated by plasma membrane transporters,
      among others a T-type (aromatic) amino acid transporter. Monocarboxylate
      transporter 10 (MCT10) has been reported to transport aromatic amino acids but
      not iodothyronines. Within the MCT family, MCT10 is most homologous to MCT8,
      which is a very important iodothyronine transporter but does not transport amino
      acids. In view of this paradox, we decided to reinvestigate the possible
      transport of thyroid hormone by human (h) MCT10 in comparison with hMCT8.
      Transfection of COS1 cells with hMCT10 cDNA resulted in 1) the production of an
      approximately 55 kDa protein located to the plasma membrane as shown by
      immunoblotting and confocal microscopy, 2) a strong increase in the affinity
      labeling of intracellular type I deiodinase by N-bromoacetyl-[(125)I]T(3), 3) a
      marked stimulation of cellular T(4) and, particularly, T(3) uptake, 4) a
      significant inhibition of T(3) uptake by phenylalanine, tyrosine, and tryptophan
      of 12.5%, 22.2%, and 51.4%, respectively, and 5) a marked increase in the
      intracellular deiodination of T(4) and T(3) by different deiodinases.
      Cotransfection studies using the cytosolic thyroid hormone-binding protein micro
      crystallin (CRYM) indicated that hMCT10 facilitates both cellular uptake and
      efflux of T(4) and T(3). In the absence of CRYM, hMCT10 and hMCT8 increased T(3)
      uptake after 5 min incubation up to 4.0- and 1.9-fold, and in the presence of
      CRYM up to 6.9- and 5.8-fold, respectively. hMCT10 was less active toward T(4)
      than hMCT8. These findings establish that hMCT10 is at least as active a thyroid
      hormone transporter as hMCT8, and that both transporters facilitate iodothyronine
      uptake as well as efflux.

PMID- 18337593
TI  - Dendritic cells in chronic obstructive pulmonary disease: new players in an old
      game.
AB  - Dendritic cells (DCs) are professional antigen-presenting cells responsible for
      immune homeostasis. In the lung's responses to tissue damage or infection, they
      initiate and orchestrate innate and adaptive immunity. There are immature and
      mature states and at least three phenotypic and functional subsets. DCs circulate
      in the blood and localize to mucosal surfaces in immature form where they act as
      sentinels, sampling constituents of the external environment that breach the
      epithelium. With internalization of antigen, they are activated, mature, and
      migrate to draining lymph nodes to induce the proliferation and regulate the
      balance of Th1/Th2 T cells or to induce a state of tolerance, the last dependent
      on maturation status, extent of cell surface costimulatory molecule expression,
      and cytokine release. Cigarette smoke has modulatory effects varying with
      species, dose, the location examined within the lung, and the marker or technique
      used to identify DCs. Healthy smokers (and smokers with asthma) have reduced
      numbers of large airway mature DCs. In chronic obstructive pulmonary disease, the
      number of immature DCs is increased in small airways, whereas in smokers with
      chronic obstructive pulmonary disease, the total number of DCs appears to be
      reduced in large airways. We hypothesize that the long-term effects of cigarette
      smoke include reduction of DC maturation and function, changes that favor
      repeated infection, increased exacerbation frequency, and the altered (CD8(+) T
      cell predominant) pattern of inflammation associated with this progressive
      chronic disease.

PMID- 18337594
TI  - Interstitial lung disease in Japanese patients with lung cancer: a cohort and
      nested case-control study.
AB  - RATIONALE: Interstitial lung disease (ILD) occurs in Japanese patients with non
      small cell lung cancer (NSCLC) receiving gefitinib. OBJECTIVES: To elucidate risk
      factors for ILD in Japanese patients with NSCLC during treatment with gefitinib
      or chemotherapy. METHODS: In a prospective epidemiologic cohort, 3,166 Japanese
      patients with advanced/recurrent NSCLC were followed for 12 weeks on 250 mg
      gefitinib (n = 1,872 treatment periods) or chemotherapy (n = 2,551). Patients who
      developed acute ILD (n = 122) and randomly selected control subjects (n = 574)
      entered a case-control study. Adjusted incidence rate ratios were estimated from
      case-control data by odds ratios (ORs) with 95% confidence intervals (CIs) using
      logistic regression. Crude (observed) incidence rates and risks were calculated
      from cohort data. MEASUREMENTS AND MAIN RESULTS: The observed (unadjusted)
      incidence rate over 12 weeks was 2.8 (95% CI, 2.3-3.3) per 1,000 person-weeks,
      4.5 (3.5-5.4) for gefitinib versus 1.7 (1.2-2.2) for chemotherapy; the
      corresponding observed naive cumulative incidence rates at the end of 12-week
      follow-up were 4.0% (3.0-5.1%) and 2.1% (1.5-2.9%), respectively. Adjusted for
      imbalances in risk factors between treatments, the overall OR for gefitinib
      versus chemotherapy was 3.2 (1.9-5.4), elevated chiefly during the first 4 weeks
      (3.8 [1.9-7.7]). Other ILD risk factors in both groups included the following:
      older age, poor World Health Organization performance status, smoking, recent
      NSCLC diagnosis, reduced normal lung on computed tomography scan, preexisting
      chronic ILD, concurrent cardiac disease. ILD-related deaths in patients with ILD
      were 31.6% (gefitinib) versus 27.9% (chemotherapy); adjusted OR, 1.05 (95% CI,
      0.3-3.2). CONCLUSIONS: ILD was relatively common in these Japanese patients with
      NSCLC during therapy with gefitinib or chemotherapy, being higher in the older,
      smoking patient with preexisting ILD or poor performance status. The risk of
      developing ILD was higher with gefitinib than chemotherapy, mainly in the first 4
      weeks.

PMID- 18337595
TI  - Atopic diseases, allergic sensitization, and exposure to traffic-related air
      pollution in children.
AB  - RATIONALE: In vitro studies, animal experiments, and human exposure studies have
      shown how ambient air pollution increases the risk of atopic diseases. However,
      results derived from observational studies are inconsistent. OBJECTIVES: To
      assess the relationship between individual-based exposure to traffic-related air
      pollutants and allergic disease outcomes in a prospective birth cohort study
      during the first 6 years of life. METHODS: We studied 2,860 children at the age
      of 4 years and 3,061 at the age of 6 years to investigate atopic diseases and
      allergic sensitization. Long-term exposure to particulate matter (PM(2.5)),
      PM(2.5) absorbance, and long-term exposure to nitrogen dioxide (NO(2)) was
      assessed at residential addresses using geographic information systems based
      regression models and air pollution measurements. The distance to the nearest
      main road was used as a surrogate for traffic-related air pollutants.
      MEASUREMENTS AND MAIN RESULTS: Strong positive associations were found between
      the distance to the nearest main road and asthmatic bronchitis, hay fever,
      eczema, and sensitization. A distance-dependent relationship could be identified,
      with the highest odds ratios (ORs) for children living less than 50 m from busy
      streets. For PM(2.5) absorbance, statistically significant effects were found for
      asthmatic bronchitis (OR, 1.56; 95% confidence interval [CI], 1.03-2.37), hay
      fever (OR, 1.59; 95% CI, 1.11-2.27), and allergic sensitization to pollen (OR,
      1.40; 95% CI, 1.20-1.64). NO(2) exposure was associated with eczema, whereas no
      association was found for allergic sensitization. CONCLUSIONS: This study
      provides strong evidence for increased risk of atopic diseases and allergic
      sensitization when children are exposed to ambient particulate matter.

PMID- 18337597
TI  - Images in clinical medicine. Green urine.

PMID- 18337596
TI  - Effect of herpes simplex suppression on incidence of HIV among women in Tanzania.
AB  - BACKGROUND: Infection with herpes simplex virus type 2 (HSV-2) is associated with
      an increased risk of acquiring infection with the human immunodeficiency virus
      (HIV). This study tested the hypothesis that HSV-2 suppressive therapy reduces
      the risk of HIV acquisition. METHODS: Female workers at recreational facilities
      in northwestern Tanzania who were 16 to 35 years of age were interviewed and
      underwent serologic testing for HIV and HSV-2. We enrolled female workers who
      were HIV-seronegative and HSV-2-seropositive in a randomized, double-blind,
      placebo-controlled trial of suppressive treatment with acyclovir (400 mg twice
      daily). Participants attended mobile clinics every 3 months for a follow-up
      period of 12 to 30 months, depending on enrollment date. The primary outcome was
      the incidence of infection with HIV. We used a modified intention-to-treat
      analysis; data for participants who became pregnant were censored. Adherence to
      treatment was estimated by a tablet count at each visit. RESULTS: A total of 821
      participants were randomly assigned to receive acyclovir (400 participants) or
      placebo (421 participants); 679 (83%) completed follow-up. Mean follow-up for the
      acyclovir and placebo groups was 1.52 and 1.62 years, respectively. The incidence
      of HIV infection was 4.27 per 100 person-years (27 participants in the acyclovir
      group and 28 in the placebo group), and there was no overall effect of acyclovir
      on the incidence of HIV (rate ratio for the acyclovir group, 1.08; 95% confidence
      interval, 0.64 to 1.83). The estimated median adherence was 90%. Genital HSV was
      detected in a similar proportion of participants in the two study groups at 6,
      12, and 24 months. No serious adverse events were attributable to treatment with
      acyclovir. CONCLUSIONS: These data show no evidence that acyclovir (400 mg twice
      daily) as HSV suppressive therapy decreases the incidence of infection with HIV.
      (Current Controlled Trials number, ISRCTN35385041 [controlled-trials.com].).

PMID- 18337598
TI  - Tuberculosis in Africa--combating an HIV-driven crisis.

PMID- 18337599
TI  - Worlds apart--tuberculosis in India and the United States.

PMID- 18337600
TI  - Anesthesia awareness and the bispectral index.
AB  - BACKGROUND: Awareness during anesthesia is a serious complication with potential
      long-term psychological consequences. Use of the bispectral index (BIS),
      developed from a processed electroencephalogram, has been reported to decrease
      the incidence of anesthesia awareness when the BIS value is maintained below 60.
      In this trial, we sought to determine whether a BIS-based protocol is better than
      a protocol based on a measurement of end-tidal anesthetic gas (ETAG) for
      decreasing anesthesia awareness in patients at high risk for this complication.
      METHODS: We randomly assigned 2000 patients to BIS-guided anesthesia (target BIS
      range, 40 to 60) or ETAG-guided anesthesia (target ETAG range, 0.7 to 1.3 minimum
      alveolar concentration [MAC]). Postoperatively, patients were assessed for
      anesthesia awareness at three intervals (0 to 24 hours, 24 to 72 hours, and 30
      days after extubation). RESULTS: We assessed 967 and 974 patients from the BIS
      and ETAG groups, respectively. Two cases of definite anesthesia awareness
      occurred in each group (absolute difference, 0%; 95% confidence interval [CI], 
      0.56 to 0.57%). The BIS value was greater than 60 in one case of definite
      anesthesia awareness, and the ETAG concentrations were less than 0.7 MAC in three
      cases. For all patients, the mean (+/-SD) time-averaged ETAG concentration was
      0.81+/-0.25 MAC in the BIS group and 0.82+/-0.23 MAC in the ETAG group (P=0.10;
      95% CI for the difference between the BIS and ETAG groups, -0.04 to 0.01 MAC).
      CONCLUSIONS: We did not reproduce the results of previous studies that reported a
      lower incidence of anesthesia awareness with BIS monitoring, and the use of the
      BIS protocol was not associated with reduced administration of volatile
      anesthetic gases. Anesthesia awareness occurred even when BIS values and ETAG
      concentrations were within the target ranges. Our findings do not support routine
      BIS monitoring as part of standard practice. (ClinicalTrials.gov number,
      NCT00281489 [ClinicalTrials.gov].).

PMID- 18337601
TI  - Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose.
AB  - BACKGROUND: Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against
      the epidermal growth factor receptor, is approved for use in colorectal cancer
      and squamous-cell carcinoma of the head and neck. A high prevalence of
      hypersensitivity reactions to cetuximab has been reported in some areas of the
      United States. METHODS: We analyzed serum samples from four groups of subjects
      for IgE antibodies against cetuximab: pretreatment samples from 76 case subjects
      who had been treated with cetuximab at multiple centers, predominantly in
      Tennessee, Arkansas, and North Carolina; samples from 72 control subjects in
      Tennessee; samples from 49 control subjects with cancer in northern California;
      and samples from 341 female control subjects in Boston. RESULTS: Among 76
      cetuximab-treated subjects, 25 had a hypersensitivity reaction to the drug. IgE
      antibodies against cetuximab were found in pretreatment samples from 17 of these
      subjects; only 1 of 51 subjects who did not have a hypersensitivity reaction had
      such antibodies (P<0.001). IgE antibodies against cetuximab were found in 15 of
      72 samples (20.8%) from control subjects in Tennessee, in 3 of 49 samples (6.1%)
      from northern California, and in 2 of 341 samples (0.6%) from Boston. The IgE
      antibodies were shown to be specific for an oligosaccharide, galactose-alpha-1,3
      galactose, which is present on the Fab portion of the cetuximab heavy chain.
      CONCLUSIONS: In most subjects who had a hypersensitivity reaction to cetuximab,
      IgE antibodies against cetuximab were present in serum before therapy. The
      antibodies were specific for galactose-alpha-1,3-galactose.

PMID- 18337602
TI  - DNA methylation markers and early recurrence in stage I lung cancer.
AB  - BACKGROUND: Despite optimal and early surgical treatment of non-small-cell lung
      cancer (NSCLC), many patients die of recurrent NSCLC. We investigated the
      association between gene methylation and recurrence of the tumor. METHODS: Fifty
      one patients with stage I NSCLC who underwent curative resection but who had a
      recurrence within 40 months after resection (case patients) were matched on the
      basis of age, NSCLC stage, sex, and date of surgery to 116 patients with stage I
      NSCLC who underwent curative resection but who did not have a recurrence within
      40 months after resection (controls). We investigated whether the methylation of
      seven genes in tumor and lymph nodes was associated with tumor recurrence.
      RESULTS: In a multivariate model, promoter methylation of the cyclin-dependent
      kinase inhibitor 2A gene p16, the H-cadherin gene CDH13, the Ras association
      domain family 1 gene RASSF1A, and the adenomatous polyposis coli gene APC in
      tumors and in histologically tumor-negative lymph nodes was associated with tumor
      recurrence, independently of NSCLC stage, age, sex, race, smoking history, and
      histologic characteristics of the tumor. Methylation of the promoter regions of
      p16 and CDH13 in both tumor and mediastinal lymph nodes was associated with an
      odds ratio of recurrent cancer of 15.50 in the original cohort and an odds ratio
      of 25.25 when the original cohort was combined with an independent validation
      cohort of 20 patients with stage I NSCLC. CONCLUSIONS: Methylation of the
      promoter region of the four genes in patients with stage I NSCLC treated with
      curative intent by means of surgery is associated with early recurrence.

PMID- 18337603
TI  - VEGF inhibition and renal thrombotic microangiopathy.
AB  - The glomerular microvasculature is particularly susceptible to injury in
      thrombotic microangiopathy, but the mechanisms by which this occurs are unclear.
      We report the cases of six patients who were treated with bevacizumab, a
      humanized monoclonal antibody against vascular endothelial growth factor (VEGF),
      in whom glomerular disease characteristic of thrombotic microangiopathy
      developed. To show that local reduction of VEGF within the kidney is sufficient
      to trigger the pathogenesis of thrombotic microangiopathy, we used conditional
      gene targeting to delete VEGF from renal podocytes in adult mice; this resulted
      in a profound thrombotic glomerular injury. These observations provide evidence
      that glomerular injury in patients who are treated with bevacizumab is probably
      due to direct targeting of VEGF by antiangiogenic therapy.

PMID- 18337604
TI  - Epigenetics in cancer.

PMID- 18337605
TI  - EGFR antagonists in cancer treatment.

PMID- 18337606
TI  - Images in clinical medicine. Erlotinib-induced hair alterations.

PMID- 18337607
TI  - Case records of the Massachusetts General Hospital. Case 8-2008. A 33-year-old
      man with fever, abdominal pain, and pancytopenia after renal transplantation.

PMID- 18337608
TI  - Depth-of-anesthesia monitor and the frequency of intraoperative awareness.

PMID- 18337609
TI  - Chemical immunosuppression in islet transplantation--friend or foe?

PMID- 18337610
TI  - TP53 mutations in head and neck cancer.

PMID- 18337611
TI  - Cetuximab for colorectal cancer.

PMID- 18337612
TI  - Addition of insulin to oral therapy in type 2 diabetes.

PMID- 18337613
TI  - Subgroup analyses in clinical trials.

PMID- 18337614
TI  - Methicillin-resistant Staphylococcus aureus in a family and its pet cat.

PMID- 18337615
TI  - Phosphatidylserine prevents UV-induced decrease of type I procollagen and
      increase of MMP-1 in dermal fibroblasts and human skin in vivo.
AB  - In an effort to find topical agents that prevent or retard cutaneous aging, seven
      functional lipids were screened for their procollagen-upregulating and matrix
      metalloproteinase (MMP)-1-downregulating activities in human dermal fibroblasts
      by Western blotting. The preventive effect on ultraviolet (UV)-induced decrease
      of procollagen was demonstrated in phosphatidylserine (PS),
      lysophosphatidylserine (LPS), lysophosphatidic acid (LPA), N-acetyl
      phytosphingosine (NAPS), and tetraacetyl phytosphingosine (TAPS). Furthermore,
      PS, LPS, and LPA upregulated procollagen expression in unirradiated basal
      conditions. The inhibitory effect on UV-induced MMP-1 expression was seen in
      NAPS, TAPS, LPA, PS, lysophosphatidylglycerol, and LPS. PS was chosen as the most
      suitable candidate anti-aging chemical for the subsequent in vivo studies. We
      investigated the effects of PS on acute UV response and chronologic skin aging by
      topically applying it to young skin before UV irradiation and to aged human skin,
      respectively. Real-time PCR and Western blot revealed that in the young skin, PS
      treatment prevented UV-induced reduction in procollagen expression and inhibited
      UV-induced MMP-1 expression. PS also blocked UV-induced IL-6 and COX-2 gene
      expression in cultured fibroblasts dose-dependently. In the aged skin, PS caused
      increased procollagen transcription and procollagen immunostaining in the upper
      dermis, and a significant decrease in MMP-1 expression at both mRNA and protein
      levels. These results indicate that topical PS has anti-skin-aging properties and
      point to the potential use of PS as a therapeutic agent in the prevention and
      treatment of cutaneous aging.

PMID- 18337616
TI  - Lipoprotein separation in a novel iodixanol density gradient, for composition,
      density, and phenotype analysis.
AB  - Separation of lipoproteins by traditional sequential salt density floatation is a
      prolonged process ( approximately 72 h) with variable recovery, whereas iodixanol
      based, self-generating density gradients provide a rapid ( approximately 4 h)
      alternative. A novel, three-layered iodixanol gradient was evaluated for its
      ability to separate lipoprotein fractions in 63 subjects with varying degrees of
      dyslipidemia. Lipoprotein cholesterol, triglycerides, and apolipoproteins were
      measured in 21 successive iodixanol density fractions. Iodixanol fractionation
      was compared with sequential floatation ultracentrifugation. Iodixanol gradient
      formation showed a coefficient of variation of 0.29% and total lipid recovery
      from the gradient of 95.4% for cholesterol and 84.7% for triglyceride. Recoveries
      for VLDL-, LDL-, and HDL-cholesterol, triglycerides, and apolipoproteins were
      approximately 10% higher with iodixanol compared with sequential floatation. The
      iodixanol gradient effectively discriminated classic lipoproteins and their
      subfractions, and there was evidence for improved resolution of lipoproteins with
      the iodixanol gradient. LDL particles subfractionated by the gradient showed good
      correlation between density and particle size with small, dense LDL (<25.5 nm)
      separated in fractions with density >1.028 g/dl. The new iodixanol density
      gradient enabled rapid separation with improved resolution and recovery of all
      lipoproteins and their subfractions, providing important information with regard
      to LDL phenotype from a single centrifugation step with minimal in-vitro
      modification of lipoproteins.

PMID- 18337617
TI  - Protecting professional composure in transcultural pediatric nursing.
AB  - In this qualitative study, we used grounded theory to explore the category of
      "overwhelming emotional expressions" that emerged in a previous study. Using
      theoretical sampling, 12 individual interviews were conducted with nurses in
      Swedish pediatric care. Overwhelming emotional expressions have been found to
      override nurses' professional preparedness; they continuously resolve this by
      protecting professional composure. Various strategies are used to protect
      professional composure, including rationalizing, controlled expression, power
      display, escape/avoidance, distancing, sharing, and management of space. Some of
      these strategies are similar to coping strategies. However, they differ in that
      they are about managing the situation and also include protecting the
      professional composure of the individual as well as the whole care situation.
      Nurses need to gain preparedness to meet overwhelming emotional expressions in
      transcultural care and to be aware of strategies for protecting professional
      composure so as to use them consciously and positively.

PMID- 18337618
TI  - HPV and cervical cancer testing and prevention: knowledge, beliefs, and attitudes
      among Hispanic women.
AB  - Cervical cancer is a preventable disease resulting from infection with high-risk
      types of sexually transmitted human papillomaviruses (HPVs). Public knowledge of
      HPVs and their link to cervical cancer is limited. Participation in cervical
      cancer prevention programs, including Pap and HPV screening and HPV vaccine
      acceptance, is crucial for limiting the incidence of cervical cancer. Hispanic
      women suffer the highest cervical cancer incidence rates in the United States. In
      this study, we conducted community-based focus groups with Hispanic women to
      explore knowledge and attitudes relating to cervical cancer, HPV, HPV testing,
      and HPV vaccination. Study findings suggest a need to increase public health
      literacy in relation to HPV, the link between HPV and cervical cancer, and HPV
      primary and secondary prevention options. Health care providers should be
      prepared to share information with patients that supports and promotes informed
      decision making about HPV testing and vaccines and their complementary roles in
      cervical cancer screening and prevention.

PMID- 18337619
TI  - Circulating adiponectin and leptin in relation to myelodysplastic syndrome: a
      case-control study.
AB  - OBJECTIVE: Adiponectin plays a protective role in several malignancies, including
      myeloblastic leukemia, whereas leptin may increase the proliferation of
      progenitor cells and may stimulate leukemic cell growth in vitro. We investigated
      the role of adiponectin and leptin levels in the etiopathogenesis of
      myelodysplastic syndromes (MDS), a preleukemic condition with increasing
      incidence which has recently been associated with obesity. METHODS: In a case
      control study, 101 cases with incident, histologically confirmed primary MDS and
      101 controls matched on gender and age were studied between 2004 and 2007, and
      blood samples were collected. RESULTS: Higher serum adiponectin levels were
      associated with lower risk of MDS by bivariate analysis and after adjusting for
      age, gender, body mass index and serum levels of leptin (p < 0.001). Subjects in
      the third quartile for leptin levels had a lower risk of MDS than controls, and
      low leptin concentrations were observed in low-risk MDS patients with normal or
      good prognostic karyotype after adjusting for age, gender and body mass index.
      CONCLUSIONS: Circulating adiponectin and leptin may play an important role in MDS
      etiopathogenesis. Future studies are needed to confirm these associations and to
      explore underlying mechanisms.

PMID- 18337620
TI  - Potential prognostic benefits of radiotherapy as an initial treatment for
      patients with unresectable advanced hepatocellular carcinoma with invasion to
      intrahepatic large vessels.
AB  - OBJECTIVES: To examine the efficacy and prognostic benefits of radiotherapy (RT)
      in patients who have unresectable advanced hepatocellular carcinoma (HCC) with
      invasion to intrahepatic large vessels (IHLVs). METHODS: Sixty-eight patients who
      had advanced HCC with invasion to IHLVs were studied. Thirty-two consecutive
      patients initially received 3-dimensional conformal RT for HCC invasion to IHLVs.
      Tumor response, prognostic factors, and survival were studied in the patients
      given RT. Prognostic factors and survival were assessed in the study group as a
      whole. Data were analyzed using the Kaplan-Meier method, univariate analysis, and
      a Cox model. RESULTS: The rate of objective response to RT was 48%. Predictors of
      survival in the patients who received RT were a hepatic function of Child-Pugh
      class A (p = 0.0263) and a response to RT (p = 0.0121). In the study group as a
      whole, independent predictors of survival in a Cox model were multinodular HCC (p
      = 0.007), inferior vena caval invasion (p = 0.001), a serum alpha-fetoprotein
      level of >1,000 ng/ml (p = 0.032), and the performance of RT (p < 0.001).
      Notably, the median survival of the nonresponders to RT (n = 15) was
      significantly longer than that of the patients who received no treatment for HCC
      (n = 21; 7.0 vs. 3.4 months, p = 0.0014). CONCLUSION: RT is considered an
      effective initial treatment for HCC invasion to IHLVs, and may offer survival
      benefits, even in nonresponders, because of the induction of stable disease.

PMID- 18337621
TI  - Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29
      colon cancer cells through inhibition of heat shock protein 27.
AB  - BACKGROUND: The purpose of this study was to investigate whether proteasome
      inhibition acts as a thermal sensitizing agent to induce tumor cell death in a
      colon cancer cell line. METHODS: HT-29 colon cancer cells were exposed to
      hyperthermia (43 degrees C) in the presence of proteasome inhibition for 1 h.
      Viable cell mass and apoptosis were measured by MTT and annexin V staining,
      respectively. Protein levels were determined by Western blot analysis. RESULTS: A
      significant synergistic effect on cell viability with proteasome inhibition was
      noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05).
      Increases in phosphorylated ERK and decreases in HSP27 levels were observed in
      the cells exposed to proteasome inhibition at 43 degrees C. Pretreatment with an
      inhibitor of ERK yielded an additional increase in apoptosis when used in
      combination with proteasome inhibition and hyperthermia. Decreased expression of
      HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death.
      CONCLUSIONS: Thermal sensitization through proteasome inhibition may represent a
      novel approach to increase the efficacy of hyperthermia as an anticancer
      modality.

PMID- 18337622
TI  - Prediction of chemosensitivity using multigene analysis in head and neck squamous
      cell carcinoma.
AB  - AIMS: The main purpose of the current study was to find predictive biomarkers
      that can be routinely used for the response to chemotherapy in head and neck
      squamous cell carcinoma (HNSCC). METHODS: From this standpoint, we selected the
      histoculture drug response assay (HDRA) to assess in vitro chemosensitivity, and
      real-time reverse transcription polymerase chain reaction to investigate the gene
      expression profile of individual tumors as available predictive biomarkers. Using
      both surgery and biopsy specimens, we analyzed their gene expression profiles
      using the 18 markers that we thought were likely predictors of the response to
      anti-cancer agents. RESULTS: Statistically significant associations were found
      between 5-fluorouracil (5-FU) sensitivity in HDRA and HER-2 mRNA expression level
      (p = 0.0030). Moreover, HER-2 expression was significantly associated with
      cisplatin sensitivity (p = 0.0089). Cisplatin sensitivity in HDRA was also
      demonstrated to have a significant association with epidermal growth factor
      receptor (EGFR) expression in which the group with cisplatin resistance tended to
      have a higher expression level than the sensitive group (p = 0.0385). CONCLUSION:
      HER-2 and EGFR may be possible reliable predictive biomarkers for anti-cancer
      therapy, and might help in the decision-making process for individual patients
      with HNSCC.

PMID- 18337623
TI  - Wnt signaling pathway in invasive ductal carcinoma of the breast: relationship
      between beta-catenin, dishevelled and cyclin D1 expression.
AB  - OBJECTIVE: The Wnt/beta-catenin signaling cascade is an important signal
      transduction pathway in human cancers. Overexpression of beta-catenin and its
      downstream effector, cyclin D1, is implicated in malignant transformation and
      acquisition of an invasive tumor phenotype. This study aimed to determine the
      clinical significance of Wnt/beta-catenin canonical pathway components in breast
      cancer. METHODS: Expression of beta-catenin, dishevelled (Dvl) and cyclin D1 was
      examined in invasive ductal carcinomas (IDCs) of the breast by
      immunohistochemical analysis. RESULTS: Of the 98 IDCs analyzed, 30% of tumors
      displayed both nuclear and cytoplasmic staining of Dvl protein, while 52% showed
      nuclear localization. Loss of cell surface beta-catenin was observed in 66% of
      breast carcinomas, whereas nuclear expression was observed in 48% IDCs. Cyclin D1
      overexpression was observed in 60% IDCs; 31/59 (53%) of these tumors showed
      nuclear expression of beta-catenin, suggesting upregulation of the canonical
      Wnt/beta-catenin pathway. Our study demonstrates a significant association
      between nuclear localization of Dvl and beta-catenin (p < 0.01, OR = 15.8).
      CONCLUSION: To our knowledge, this is the first study showing an association
      between nuclear localization of Dvl and beta-catenin in IDCs and suggests the
      upregulation of Wnt/beta-catenin pathway components, beta-catenin, Dvl and cyclin
      D1 in IDCs of the breast.

PMID- 18337624
TI  - CYR61 downregulation correlates with tumor progression by promoting MMP-7
      expression in human gastric carcinoma.
AB  - OBJECTIVE: CYR61 (cysteine-rich 61) belongs to the CCN (CYR61/CTGF/NOV) protein
      family and is involved in tumorigenesis. We have previously confirmed that the
      level of CYR61 protein is decreased in gastric carcinoma compared with nontumoral
      mucosa, by conducting proteome-based analyses. In this study, we examine the
      relationship between CYR61 expression and clinicopathological data of MMP-7
      expression in human gastric mucosae and tumors. METHODS: Immunohistochemical
      and/or immunofluorescence analyses were performed to examine the histological
      expression of CYR61 in normal gastric mucosa, intestinal metaplasia, 33 adenomas,
      and 127 carcinomas. Seven gastric carcinoma cell lines were used to examine the
      expression of CYR61 and MMP-7 by Western blotting. RESULTS: The CYR61-expressing
      cells mostly coincided with the serotonin-containing cells, not only in
      nontumoral epithelia, but also among tumor cells. CYR61 expression was positive
      (labeling index: >2%) in 43 of 49 early gastric carcinomas (87.8%) and in 19 of
      78 advanced gastric carcinomas (24.4%), the frequency being significantly lower
      in the latter (p < 0.001). All the normal mucosae, intestinal metaplasias and
      adenomas were in the positive group. The reduction in CYR61 expression correlated
      significantly with histological differentiation (p < 0.05), depth of invasion (p
      < 0.001), lymphatic invasion (p < 0.001), venous invasion (p < 0.001), lymph node
      metastasis (p < 0.001) and clinical stage (p < 0.001). Immunohistochemistry and
      Western blotting revealed the expression of CYR61 to be inversely correlated with
      that of MMP-7 (p < 0.001). CONCLUSIONS: CYR61 is expressed in serotonin
      containing cells, and downregulation of the expression might contribute to the
      progression of cancer by promoting MMP-7 expression in human gastric carcinomas.

PMID- 18337625
TI  - Persistent erythema multiforme in a patient with extrahepatic cholangiocarcinoma.
AB  - Presented in this report is a 66-year-old male with a widespread persistent
      erythema multiforme mostly atypical in appearance, which was detected well before
      the diagnosis of underlying extrahepatic cholangiocarcinoma. The lesions
      regressed in response to chemotherapy, but they appeared again in connection with
      tumor relapse. Clinicians should recognize persistent erythema multiforme as one
      of the paraneoplastic dermatoses and efforts should be made to detect internal
      malignancies in patients with these skin lesions.

PMID- 18337626
TI  - Treatment of transformed mycosis fungoides with intermittent low-dose
      gemcitabine.
AB  - The malignant helper T cells of mycosis fungoides, a type of cutaneous T cell
      lymphoma, are capable of transforming into large cerebriform cells. Large cell
      transformation usually renders the disease more resistant to treatment and prone
      to relapse. Currently investigated treatment modalities for transformed mycosis
      fungoides are few and include phototherapy, chemotherapy, biologic response
      modification, targeted molecular therapy and combinations thereof. A tolerable
      and reliable modality has yet to be identified. Gemcitabine, a novel purine
      analogue, is gaining recognition as a potent agent for advanced nontransformed
      cutaneous T cell lymphoma. Here we present a brief review of the literature with
      3 illustrative cases that additionally reveal gemcitabine monotherapy to be a
      practical, safe and efficacious option for mycosis fungoides that has undergone
      large cell transformation.

PMID- 18337627
TI  - Occurrence of synchronous invasive lobular breast carcinoma and poorly
      differentiated ovarian carcinoma in a single peritoneal deposit.
AB  - The synchronous occurrence of breast and ovarian cancers within individual
      omental metastases has not been reported in the available medical literature. We
      report such a finding in a patient with previously diagnosed invasive lobular
      carcinoma of the right breast. After 5 years of surveillance and disease-free
      interval, there was development of ovarian cancer, ascites and peritoneal
      metastases. Ultrasound-guided biopsy of a peritoneal metastasis confirmed dual
      histology from breast and ovarian carcinoma. Despite the presence of a prolonged
      disease-free survival from the primary breast cancer, the subsequent finding of
      advanced ovarian cancer highlights the potential diagnostic and therapeutic
      dilemmas which persist in the management of these patients.

PMID- 18337628
TI  - Attention bias in children of patients with panic disorder.
AB  - Cognitive models of panic disorder have emphasized the role of cognitive
      distortions in the maintenance of this disorder. Several studies have produced
      results consistent with this hypothesis, but it is still unclear whether
      cognitive biases precede anxiety disorders or whether they are a consequence of
      the disorder. In the present study, we compared children of individuals with
      panic disorder, children of individuals with animal phobia, and children of
      normal controls with respect to attentional bias with an emotional Stroop task,
      which included three types of words: panic-relevant, animal phobia-relevant, and
      neutral words. Our results revealed that children of panic patients did not show
      an attentional bias for panic-relevant stimuli. Results will be discussed in the
      context of theoretical models explaining the etiological factor of cognitive
      biases for the development of anxiety disorders.

PMID- 18337629
TI  - Frequency of dysphoria and mixed states.
AB  - BACKGROUND: Mixed states are a complex entity in the field of mood disorders.
      Dysphoria has been advocated as an important clinical dimension of mixed states.
      The objective of this work is to study the frequency of dysphoria within a
      population of patients with DSM-IV major depressive and/or manic episodes and to
      determine if it may help establish diagnostic criteria for subthreshold cases of
      depressive or manic mixed states. SAMPLING AND METHODS: A total of 165 patients
      were assessed using the Mini International Neuropsychiatric Interview
      complemented by a section defining dysphoria as a constellation of 3 among 4
      symptoms (inner tension, irritability, aggressive behavior and hostility).
      RESULTS: When classifying patients according to the number of symptoms of the
      opposite polarity, changes in the frequency of dysphoria revealed a clear
      contrast between the 2 opposite manic and depressive poles and the full mixed
      state (DSM-IV definition). The frequency of dysphoria was 17.5% in pure
      depression, 22.7% in pure mania and 73.3% in full mixed state. Two threshold
      effects were identified: (1) the frequency of dysphoria increased from 17.5 to
      61.1% (p = 0.002) when the number of manic symptoms in DSM-IV depressed patients
      increased from 0 to 1, and (2) dysphoria increased from 14.3 to 69.2% (p = 0.057)
      when the number of depressive symptoms increased from 2 to 3 in DSM-IV manic
      patients. CONCLUSION: Dysphoria is strongly but not necessarily associated with
      mixed states. When used as a clinical marker for mixed states, dysphoria confirms
      the modern delimitations of sub-threshold mixed states by specifying the required
      number of symptoms of the opposite polarity (which could be lower for depressive
      mixed states than for manic mixed states). The study has limitations related to
      the inclusion of patients who are not drug-free, to the definition of dysphoria
      and to the sample size.

PMID- 18337630
TI  - Social and communication difficulties and obsessive-compulsive disorder.
AB  - BACKGROUND: The relationship between pervasive developmental disorder (PDD) and
      obsessive-compulsive disorder (OCD) has not been extensively studied despite
      having some phenomenological features in common. Abnormal social and
      communication behaviors (pragmatic behaviors) are key components of PDD and are
      also part of the broader autism phenotype (BAP). In this study we sought to
      establish if there is any association between the presence of abnormal pragmatic
      behaviors and OCD and whether this association delineates a familial subtype of
      OCD. SAMPLING AND METHODS: As part of the Johns Hopkins OCD Family Study, 80 OCD
      case probands were recruited and matched with 73 control probands. Probands and
      their first-degree relatives were interviewed using the Schedule for Affective
      Disorders and Schizophrenia-Lifetime Anxiety and other diagnostic instruments. A
      Pragmatic Rating Scale (PRS) to assess pragmatic behaviors was completed by the
      examiner. RESULTS: The PRS was completed on 395 subjects, of which 3% (n = 11)
      achieved a score of greater than 6. The prevalence of high PRS scores was
      significantly greater amongst case probands and relatives (5%) compared to
      control probands and relatives (0.5%, p = 0.011). In case relatives the
      prevalence of OCD was significantly higher in those relatives who had a family
      member with a high PRS score (p < 0.001). CONCLUSIONS: The presence of social and
      communication difficulties in members of OCD case families appears to identify a
      familial subtype of OCD that may be related to PDD and/or BAP. This study was
      limited to using the PRS to identify pragmatic behaviors in subjects with OCD.

PMID- 18337631
TI  - Contour copying or echoplasia--a new echo phenomenon in a person with Gilles de
      la Tourette syndrome.

PMID- 18337632
TI  - Effects of housing characteristics and home environmental factors on respiratory
      symptoms of 10,784 elementary school children from northeast china.
AB  - BACKGROUND: Only few studies have assessed the relative impact of housing
      characteristics and home environmental factors on asthma and asthma-related
      symptoms in Chinese children, and to our knowledge, few studies have elaborated
      respiratory symptoms and allergies in this context. OBJECTIVE: It was the aim of
      this study to assess the effects of housing characteristics, pet keeping, home
      decorations and other indoor environmental factors on respiratory health of
      Chinese children. METHODS: We studied 10,784 children (6-13 years old) from 12
      districts in Liaoning province, Northeast China. Information on respiratory
      health, housing characteristics and environmental pollution was obtained by a
      standard questionnaire from the American Thoracic Society. RESULTS: Prevalence of
      asthma-related symptoms was higher for those living along the main stem of
      traffic, and for those with a house nearby a pollution source. Lower prevalence
      rates of respiratory morbidity were associated with households with a bigger area
      of residence and more rooms. Pet keeping was associated with doctor-diagnosed
      asthma (OR = 1.52; 95% CI 1.25-1.84). Home decorations also increased the risk of
      doctor-diagnosed asthma (OR = 1.72; 95% CI 1.45-2.04) and current asthma (OR =
      1.43; 95% CI 1.06-1.93). Environmental tobacco smoke, pests and visible mold on
      walls were associated with the occurrence of asthma symptoms. CONCLUSION: Home
      environmental factors are particularly important for the development of
      respiratory morbidity among children.

PMID- 18337633
TI  - Increased susceptibility to oxidant-mediated tissue injury and peritoneal
      fibrosis in acatalasemic mice.
AB  - BACKGROUND: Peritoneal fibrosis is a major complication leading to the loss of
      peritoneal function in patients undergoing peritoneal dialysis. However, the
      effect of catalase depletion on peritoneal fibrosis has not yet been
      investigated. METHODS: The impact of catalase deficiency on progressive
      peritoneal fibrosis has been studied in homozygous acatalasemic mutant mice or
      control wild-type mice by intraperitoneal injection of chlorhexidine gluconate
      (CG) every other day for 14 days. RESULTS: The CG injections resulted in a
      thicker peritoneal membrane, reflecting peritoneal fibrosis with accumulation of
      interstitial type I collagen, peritoneal deposition of lipid peroxidation
      products (4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal), and an elevated level of
      8-hydroxy-2'-deoxyguanosine in peritoneal fluid in both mouse groups on day 14.
      The extent of these changes, however, was significantly higher in acatalasemic
      mice than in wild-type mice. The level of catalase activity remained low in the
      acatalasemic peritoneum without the compensatory upregulation of glutathione
      peroxidase, but with an insufficient upregulation of superoxide dismutase
      activity in CG-injected mice. CONCLUSIONS: Acatalasemia, therefore, exacerbates
      oxidant tissue injury and induces the peritoneum to develop irreversible fibrosis
      which is the most important complication of peritoneal dialysis. This study
      suggests that catalase plays a crucial role in the defense against oxidant
      mediated peritoneal injury in a mouse peritoneal fibrosis model.

PMID- 18337634
TI  - Is fetuin-A/alpha2-Heremans-Schmid glycoprotein associated with the metabolic
      syndrome in patients with chronic kidney disease?
AB  - INTRODUCTION: Components of the metabolic syndrome are highly prevalent in
      chronic kidney disease (CKD) patients--some of which paradoxically appear to
      predict an improved outcome in this population. We hypothesized that the
      circulating calcification inhibitor fetuin-A/AHSG, which is also a natural
      inhibitor of the tyrosine kinase insulin receptor, could be one factor explaining
      the association between increased fat mass and a survival advantage in CKD and
      thus conducted an explorational study to provide preliminary data to support
      further research into this hypothesis. PATIENTS AND METHODS: In a cross-sectional
      study, we evaluated 198 CKD stage 5 patients (GFR 6.8 +/- 0.2 ml/min; 62% males,
      mean age 52 +/- 1 years) close to the start of renal replacement therapy. We
      studied circulating AHSG (ELISA) and two common functional AHSG gene
      polymorphisms (at amino acids Thr248Met (C-T) and Thr256Ser (C-G) using
      Pyrosequencing) and related these to multiple components of the metabolic
      syndrome. RESULTS: Median circulating AHSG was lower (p < 0.01) in type-2 (0.22
      g/l) and type-1 (0.16 g/l) diabetics as compared to non-diabetic CKD-5 patients
      (0.24 g/l). AHSG correlated with both total and truncal fat mass in type-2
      diabetics (rho 0.37 and 0.39; p < 0.001, respectively), but not in type-1
      diabetics or non-diabetics. Both SNPs significantly influenced circulating levels
      of AHSG, and were also associated with significant differences in serum
      triglycerides and HDL cholesterol. Furthermore, there were significant
      differences in the prevalence of metabolic syndrome criteria between the AHSG
      Thr256Ser (C-G) genotype groups, with a more atherogenic lipid profile in AHSG
      high producers (Thr/Thr homozygotes). In multivariate analysis, the association
      between circulating AHSG and fat mass remained significant also after adjustment
      for age, gender, inflammation (CRP >10 mg/l), and AHSG genotype. CONCLUSIONS: The
      present, explorational, study supports further, mechanistic, studies into a
      physiological link between AHSG and body fat mass in patients with CKD. As we
      observed an association between higher fat mass and elevated AHSG levels, these
      preliminary results may form the basis of further study to establish if the
      observed associations may be one reason why obesity has been reported to
      constitute a survival advantage in CKD.

PMID- 18337635
TI  - Risk factor profile and management of cerebrovascular patients in the REACH
      Registry.
AB  - BACKGROUND: Cerebrovascular disease (CVD) is a global public health problem. CVD
      patients are at high risk of recurrent stroke and other atherothrombotic events.
      Prevalence of risk factors, comorbidities, utilization of secondary prevention
      therapies and adherence to guidelines all influence the recurrent event rate. We
      assessed these factors in 18,992 CVD patients within a worldwide registry of
      stable outpatients. METHODS: The Reduction of Atherothrombosis for Continued
      Health Registry recruited >68,000 outpatients (44 countries). The subjects were
      mainly recruited by general practitioners (44%) and internists (29%) if they had
      symptomatic CVD, coronary artery disease, peripheral arterial disease (PAD)
      and/or >or=3 atherothrombotic risk factors. RESULTS: The 18,992 CVD patients
      suffered a stroke (53.7%), transient ischemic attack (TIA) (27.7%) or both
      (18.5%); 40% had symptomatic atherothrombotic disease in >or=1 additional
      vascular beds: 36% coronary artery disease; 10% PAD and 6% both. The prevalence
      of risk factors at baseline was higher in the TIA subgroup than in the stroke
      group: treated hypertension (83.5/82.0%; p = 0.02), body mass index >or=30
      (26.7/20.8%; p < 0.0001), hypercholesterolemia (65.1/52.1%; p < 0.0001), atrial
      fibrillation (14.7/11.9%; p < 0.0001) and carotid artery disease (42.3/29.7%; p <
      0.0001). CVD patients received antiplatelet agents (81.7%), oral anticoagulants
      (17.3%), lipid-lowering agents (61.2%) and antihypertensives (87.9%), but
      guideline treatment targets were frequently not achieved (54.5% had elevated
      blood pressure at baseline, while 4.5% had untreated diabetes). CONCLUSIONS: A
      high percentage of CVD patients have additional atherothrombotic disease
      manifestations. The risk profile puts CVD patients, especially the TIA subgroup,
      at high risk for future atherothrombotic events. Undertreatment is common
      worldwide and adherence to guidelines needs to be enforced.

PMID- 18337636
TI  - Blood levels of brain-derived neurotrophic factor correlate with several
      psychopathological symptoms in anorexia nervosa patients.
AB  - BACKGROUND: Evidence of a role of brain-derived neurotrophic factor (BDNF) in the
      pathophysiology of eating disorders (ED) has been provided by association studies
      and by murine models. BDNF plasma levels have been found altered in ED and in
      psychiatric disorders that show comorbidity with ED. AIMS: Since the role of BDNF
      levels in ED-related psychopathological symptoms has not been tested, we
      investigated the correlation of BDNF plasma levels with the Symptom Checklist 90
      Revised (SCL-90R) questionnaire in a total of 78 ED patients. METHODS: BDNF
      levels, measured by the enzyme-linked immunoassay system, and SCL-90R
      questionnaire, were assessed in a total of 78 ED patients. The relationship
      between BDNF levels and SCL-90R scales was calculated using a general linear
      model. RESULTS: BDNF plasma levels correlated with the Global Severity Index and
      the Positive Symptom Distress Index global scales and five of the nine subscales
      in the anorexia nervosa patients. BDNF plasma levels were able to explain, in the
      case of the Psychoticism subscale, up to 17% of the variability (p = 0.006).
      CONCLUSION: Our data suggest that BDNF levels could be involved in the severity
      of the disease through the modulation of psychopathological traits that are
      associated with the ED phenotype.

PMID- 18337637
TI  - Association of MAO-A variant with complicated grief in major depression.
AB  - BACKGROUND/AIMS: It has been suggested that monoamine oxidase A (MAO-A) activity
      is involved in the pathogenesis of major depression. Bereavement-related
      complicated grief significantly increases the risk of major depression and has
      been shown to be influenced by serotonergic tonus, possibly conferred by MAO-A
      activity. Complicated grief--whose inclusion in DSM-V as a separate mental
      disorder is under discussion--has been shown to be a distinct syndrome with
      symptoms not seen in depression. Therefore, in the present study, genetic
      variation in the MAO-A gene was investigated for its influence on complicated
      grief in major depression. METHODS: Sixty-six unrelated Caucasian patients (41
      female, 25 male) with major depression and a history of bereavement were
      evaluated for complicated grief using the Inventory of Complicated Grief (ICG),
      the posttraumatic stress reaction after the loss by means of the Impact of Event
      Scale (IES-R) and further psychopathological measures. Patients were additionally
      genotyped for the functional variable number tandem repeat (VNTR) in the promoter
      region of the MAO-A gene. RESULTS: The more active longer allele of the MAO-A
      VNTR was significantly associated with complicated grief in the female subgroup
      of patients (chi(2) = 9.471, p = 0.002, OR = 9.208, 95% CI 2.129-38.899,
      Bonferroni-corrected p = 0.012), whereas there was no such effect in male
      patients. Higher posttraumatic stress reaction was only nominally associated with
      the more active longer allele of the MAO-A VNTR in the female subgroup of
      patients (genotypes: chi(2) = 5.939, p = 0.015, OR = 5.333, 95% CI 1.366-20.557,
      Bonferroni-corrected p = 0.087). No significant associations of MAO-A VNTR with
      the severity of depressive symptoms (Beck Depression Inventory), anxiety symptoms
      (Spielberger State-Trait Anxiety Inventory), general mental health (Brief Symptom
      Inventory), or perceived social support (F-SozU) were found (all p > 0.10).
      CONCLUSION: The present pilot study for the first time suggests a gender-specific
      contribution of the more active MAO-A VNTR variant to an increased vulnerability
      for complicated grief as a potential intermediate phenotype of major depression.

PMID- 18337638
TI  - Effects of dietary caffeine on topographic EEG after controlling for withdrawal
      and withdrawal reversal.
AB  - BACKGROUND/AIMS: Despite several decades of research into the effects of caffeine
      on EEG, few consistent findings have emerged. Notwithstanding the likelihood that
      differences in methodology may explain some of the inconsistency, confidence in
      the published findings is undermined by the failure in previous studies to
      control for the effects of caffeine withdrawal and withdrawal reversal. METHODS:
      Participants (n = 22) alternated weekly between ingesting placebo and caffeine
      (1.75 mg/kg) 3 times daily for 4 consecutive weeks. EEG activity was measured at
      32 sites during eyes closed, eyes open, and performance of a vigilance task.
      RESULTS: Caffeine was found to have few and modest effects on EEG in the theta
      and alpha bandwidths, and no effects in the delta and beta bandwidths. Evidence
      was found of withdrawal, withdrawal reversal, and tolerance in relation to
      observed increases in theta power during task performance; withdrawal and
      withdrawal reversal in relation to increases in alpha power during all three
      behavioural conditions (eyes closed, eyes open, and task performance), and
      withdrawal-induced adverse effects in relation to aspects of subjective mood.
      CONCLUSION: The finding of similar increases in theta power following caffeine
      challenge and acute caffeine withdrawal casts doubt on whether caffeine may be
      viewed as having direct stimulant effects. Results could suggest that change in
      drug state, whether in the form of acute caffeine withdrawal or challenge, may be
      disruptive to electrophysiological activity in the brain.

PMID- 18337639
TI  - Controversies in endocrine treatment: effective utilization of steroidal and
      nonsteroidal aromatase inhibitors: now and in the future. Forward.

PMID- 18337640
TI  - Exploring the lack of cross-resistance between aromatase inhibitors: evidence for
      a difference?
AB  - A lack of cross-resistance between the aromatase inhibitors (AIs) provides
      evidence to suggest that there are clinical differences between these agents.
      Available data from clinical trials indicate that patients exposed to
      nonsteroidal AIs may benefit from a steroidal compound of similar biochemical
      potency, and durable stable disease can be achieved in a significant proportion
      of patients. To date, there is little evidence suggesting specific
      pharmacokinetic/pharmacodynamic resistance for individual tumours to particular
      compounds. To clarify fully this issue, a head-to-head comparative trial in the
      adjuvant setting is needed and the results of the MA.27 trial randomizing
      patients to the steroidal AI exemestane vs. the nonsteroidal AI anastrozole will
      be invaluable in this regard.

PMID- 18337641
TI  - Addressing the future: combination with targeted therapies, adjuvant setting and
      beyond.
AB  - The potential mechanisms of de novo and acquired resistance to endocrine therapy
      are increasingly being understood and potential treatment options that offer a
      therapeutic alternative in patients exhibiting resistance are being explored. Any
      efforts directed towards improving patient outcomes beyond aromatase inhibitors
      (AIs) in the adjuvant setting are likely to be focused on blocking endocrine and
      other pathways simultaneously, either upfront or in sequence. In particular,
      targeted therapies either alone or in combination with AIs may improve clinical
      outcomes--the results of ongoing clinical trials will shape the future treatment
      of breast cancer.

PMID- 18337642
TI  - The similarities of aromatase inhibitors outweigh the differences.
AB  - Although the aromatase inhibitors (AIs) as a class exhibit clear differences in
      terms of their structure and mechanism of action, these differences do not always
      translate into clinically significant differences in patient outcomes. In fact,
      these differences may actually reflect differences in clinical trial design (i.e.
      upfront, sequential or switch therapy) or the patient population studied. The
      results of clinical trials demonstrate a clear superiority of third-generation
      AIs over tamoxifen. It will, however, be necessary to wait for the results of the
      ongoing head-to-head MA.27 and Novartis trials to determine whether there is any
      differentiation between the various third-generation AIs.

PMID- 18337643
TI  - A single chain immunotoxin, targeting the melanoma-associated chondroitin sulfate
      proteoglycan, is a potent inducer of apoptosis in cultured human melanoma cells.
AB  - A recombinant immunotoxin was constructed by fusing a single chain fragment
      variable antibody fragment, specific for the melanoma-associated chondroitin
      sulfate proteoglycan (MCSP), to a truncated variant of Pseudomonas exotoxin A
      (ETA'), carrying a C-terminal KDEL-peptide for improved retrograde intracellular
      transport. The resulting immunotoxin MCSP-ETA' was periplasmatically expressed in
      Escherichia coli and purified under native conditions by affinity chromatography
      resulting in a yield of approximately 30 mug/l bacterial culture. This
      immunotoxin induced antigen-specific apoptosis in the cultured human melanoma
      derived cell lines A2058 and A375M, and treatment with a single dose of the agent
      eliminated up to 80% of these cells within 72 h. The dose needed for half-maximum
      killing (EC50) was approximately 1 nmol/l for both cell lines. MCSP-ETA' also
      displayed cytotoxic activity against cultured primary melanoma cells from
      patients with advanced disease (pathologic stages IIIC and IV), with net cell
      death reaching up to 70% within 96 h after treatment with a single dose of 14
      nmol/l. MCSP-ETA' induced cell death synergistically with cyclosporin A, both in
      established human melanoma cell lines and cultured primary melanoma cells. The
      distinctive antigen-restricted induction of apoptosis and the synergy with
      cyclosporin A justify further evaluation of this novel agent with regard to its
      potential application for the treatment of malignant melanoma.

PMID- 18337644
TI  - Simvastatin inhibits growth via apoptosis and the induction of cell cycle arrest
      in human melanoma cells.
AB  - Competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the
      statins) that inhibit the synthesis of mevalonic acid are in wide use for
      treatment of hypercholesterolemia. Although antitumor effects on a variety of
      cell types have been reported for statins, the effect of simvastatin (one of the
      statins) on human melanoma cell lines is not known. Here, we report antitumor
      effects of simvastatin on human melanoma cell lines. We treated human melanoma
      cell lines, A375M, G361, C8161, GAK, and MMAc with simvastatin in various
      concentrations for 1 to 3 days. To investigate the antitumor effect of
      simvastatin, we analyzed cell viability, morphologic changes, reversibility of
      inhibition by geranylgeranyl pyrophosphate and farnesyl pyrophosphate, apoptosis
      and the cell cycle. Simvastatin treatment reduced cell viability in all five
      melanoma cell lines. The different melanoma cell lines, however, displayed
      different sensitivities to simvastatin. The addition of geranylgeranyl
      pyrophosphate to A375M and G361 cells in the presence of simvastatin completely
      restored the viability of cells, but the addition of farnesyl pyrophosphate did
      not. DNA fragmentation assay showed that simvastatin induced apoptosis in A375M
      and G361 cells. Simvastatin caused a G1 arrest in G361 and MMAc cells. Consistent
      with the cell cycle arrest, simvastatin caused an increase in the mRNA levels of
      p21 and p27 on G361 and MMAc cells. We conclude that simvastatin has an antitumor
      effect on human melanoma cells in vitro via apoptosis and cell cycle arrest.
      These results suggest that simvastatin may be an effective anticancer drug for
      malignant melanoma.

PMID- 18337645
TI  - In-vivo xenograft murine human uveal melanoma model develops hepatic
      micrometastases.
AB  - The purpose of the study is to develop a mouse ocular melanoma model with human
      uveal melanoma cells that forms hepatic micrometastases. Human uveal melanoma
      Mel290 cells were transfected with a lentiviral-enhanced green fluorescent
      protein (EGFP) expression vector. Proliferation assays were performed by
      comparing Mel290-EGFP and Mel290 cells. After stable expression of EGFP and
      proliferation was ascertained, 1 x 10 Mel290-EGFP cells were introduced into
      NU/NU mice by posterior compartment (PC) inoculation or tail vein injection.
      Control groups were inoculated or injected with Mel290 cells. Ocular and hepatic
      frozen sections were examined by fluorescence microscopy, and the number of
      hepatic micrometastases was determined. EGFP expression was observed at 24 h
      after transfection. At 72 h after transfection, more than 70% of Mel290 cells
      expressed EGFP. At 45 days (six passages), 90% of Mel290 cells stably expressed
      EGFP. Histologic examination showed that Mel290-EGFP cells formed hepatic
      micrometastases after either PC inoculation or tail vein injection. A significant
      difference in the number of hepatic micrometastases between PC inoculation and
      tail vein injection (P<0.01) was observed. Mel290-EGFP cells stably expressed
      green fluorescent protein in vitro at 45 days (six passages). These cells formed
      hepatic micrometastases in NU/NU mice after PC inoculation or tail vein
      injection, with significantly more micrometastases developing in the PC
      inoculation model than after tail vein injection.

PMID- 18337646
TI  - Clinical phase I intratumoral administration of two recombinant ALVAC canarypox
      viruses expressing human granulocyte-macrophage colony-stimulating factor or
      interleukin-2: the transgene determines the composition of the inflammatory
      infiltrate.
AB  - Immunotherapy employs cytokines for modifying local inflammatory reactions.
      Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been shown to
      activate dendritic cells, macrophages, and granulocytes leading to clinical
      trials using GM-CSF-based cancer vaccine approaches. Interleukin-2 (IL-2) is an
      important T cell stimulatory cytokine approved as exogenous antitumor agent. The
      ALVAC viral vector system uses a recombinant canarypox virus for local gene
      expression. We report a phase I clinical trial using intratumoral administration
      of ALVAC GM-CSF or ALVAC IL-2 in skin metastases of melanoma or leiomyosarcoma.
      ALVAC GM-CSF and ALVAC IL-2 were injected at 107.12 and 106.92, 50% cell culture
      infectious dose in eight metastases with acceptable tolerability. Local and
      systemic inflammatory reactions were observed. The transgene determined the local
      infiltrate: GM-CSF induced monocyte and macrophage enrichment of the peritumoral
      inflammatory infiltrate, whereas IL-2 increased local T lymphocytes. Stable
      disease of injected lesions was seen after ALVAC GM-CSF application, whereas
      ALVAC IL-2 treatment led to partial regression in three out of eight injected
      tumors, accompanied by decreased expression of melanocytic antigens. Local GM-CSF
      expression could be induced. In summary, ALVAC GM-CSF and ALVAC IL-2 injections
      are safe and can mediate local biologic and immunologic effects.

PMID- 18337647
TI  - Management of primary and metastasized melanoma in Germany in the time period
      1976-2005: an analysis of the Central Malignant Melanoma Registry of the German
      Dermatological Society.
AB  - This study analysed the changes of excision margins in correlation with tumour
      thickness as recorded over the last three decades in Germany. The study also
      evaluated surgical management in different geographical regions and treatment
      options for metastasized melanoma. A total of 42 625 patients with invasive
      primary cutaneous melanoma, recorded by the German Central Malignant Melanoma
      Registry between 1976 and 2005 were included. Multiple linear regression analysis
      was used to investigate time trends of excision margins adjusted for tumour
      thickness. Excision margins of 5.0 cm were widely used in the late 1970s but
      since then have been replaced by smaller margins that are dependent on tumour
      thickness. In the case of primary melanoma, one-step surgery dominated until 1985
      and was mostly replaced by two-step excisions since the early 1990s. In eastern
      Germany, one-step management remained common until the late 1990s. During the
      last three decades loco-regional metastases were predominantly treated by surgery
      (up to 80%), whereas systemic therapy decreased. The primary treatment of distant
      metastases has consistently been systemic chemotherapy. This descriptive
      retrospective study revealed a significant decrease in excision margins to a
      maximum of 2.00 cm. A significant trend towards two-step excisions in primary
      cutaneous melanoma was observed throughout Germany. Management of metastasized
      melanoma showed a tendency towards surgical procedures in limited disease and an
      ongoing trend to systemic treatment in advanced disease.

PMID- 18337648
TI  - Isolated hepatic perfusion for liver metastases of malignant melanoma.
AB  - The objective was to analyze the outcome of three treatment strategies using
      isolated hyperthermic liver perfusion (IHP) with melphalan for liver metastases
      of malignant melanoma. It was designed as an exploratory study. The setting was a
      single-center study in a university hospital. The study was carried out on 27
      patients. IHP was used with modifications during three different time periods
      (IHP I, IHP II and IHP III), in technique and temperature (amount of melphalan:
      0.5, 1.0 and 2 mg/kg body weight in the perfusate; 41, 40 and 40 degrees C).
      Tumor response was estimated according to WHO criteria with computed tomography
      or MRI. Mortality and morbidity were secondary measures. Six of 11 patients in
      the IHP I cohort experienced a partial response (PR). In the IHP II cohort, two
      patients of 11 experienced a complete response and five a PR. In the IHP III
      cohort, five of five patients experienced a PR. Six postoperative deaths were
      reported (27%) (three in the IHP I and three in the IHP II series), secondary to
      liver insufficiency and multiorgan failure. Treatment of liver metastases of
      malignant melanoma with isolated hyperthermic melphalan perfusion has shown an
      impressive tumor response rate, which seems to be higher than the response rates
      reported for other systemic chemotherapy regimens. The maximum tolerated dose for
      melphalan in the perfusate was surpassed with a 2 mg/kg body weight. By modifying
      the technique and restricting the allowed tumor burden, the response rate
      remained high and the mortality was reduced.

PMID- 18337649
TI  - Vulvar melanoma: a report of 10 cases and review of the literature.
AB  - Despite its low incidence, vulvar melanoma carries a poor prognosis and shows a
      high tendency to metastasize because the diagnosis is often delayed. Although it
      is very well known that ultraviolet radiation is an important aetiological factor
      for cutaneous melanomas in adults, this cannot be considered true for vulvar
      melanoma. Chronic inflammatory disease, viral infections, irritant agents are the
      main factors suspected to induce mucosal melanoma. We report 10 cases of vulvar
      malignant melanoma observed in our institute from 1990 to 2005 and a review of
      the literature.

PMID- 18337650
TI  - S100B in bone marrow aspirates in healthy individuals and malignant melanoma
      patients.
AB  - The aim of this study was to evaluate S100B in bone marrow (BM) plasma from
      malignant melanoma patients. BM aspirates and peripheral blood (PB) plasma from
      56 patients and BM aspirates from 29 healthy volunteers were collected. S100B was
      measured using an immune radiometric assay, which is a two-site sandwich assay
      based on monoclonal antibodies recognizing the beta-subunit. In the control
      population, the median S100B level in BM plasma was 9.0 microg/l (26 women and
      three men), an unexpectedly high value compared with the median S100B level in
      PB<0.05 microg/l. S100B levels in BM seems to be sex dependent. Median S100B
      levels in samples taken from male melanoma patients was 26.7 microg/l in contrast
      to 9.3 microg/l in female patients (Mann-Whitney P<0.002). The elevated BM S100B
      in melanoma patients could not be explained by presence of melanoma cells in the
      BM, as the values also were increased to the same extent in patients with no
      detectable BM metastases. In attempts to identify the source of S100B in BM,
      cytospins from five patients with high S100B values were stained, but none of the
      BM cells stained positive. S100B levels in PB were dependent on the stage of
      melanoma disease and there was a significant shorter survival time in the group
      of patients with elevated S100B compared with the group with normal S100B values,
      (log rank test: P=0.04). In BM taken from melanoma patients, however, there were
      no association between S100B levels and survival. The median S100B level in BM
      aspirates from healthy female volunteers and BM samples from female melanoma
      patients were 8.1 and 9.3 microg/l both manifold higher than the cut-off value
      for S100B in PB (0.2 microg/l). The median S100B in the samples taken from male
      melanoma patients was nearly three times higher than in the female patients.
      Unlike S100B in PB, S100B in BM demonstrated no prognostic value. The explanation
      for the unexpected high S100B in BM remains elusive.

PMID- 18337651
TI  - Temozolomide associated with PEG-interferon in patients with metastatic melanoma:
      a multicenter prospective phase I/II study.
AB  - Metastatic melanoma treatment remains disappointing, and a combined approach by
      chemotherapy and immunotherapy might increase the response rates through a
      synergistic action. Accordingly, a clinical trial using oral temozolomide (TMZ)
      and subcutaneous PEG-interferon alpha-2b (PEG) in patients with metastatic
      melanoma was designed to determine the maximal tolerated dosage of both drugs and
      the antitumoral response. A multicenter, prospective, phase I/II study was
      conducted in 31 metastatic melanoma patients, without cerebral metastasis. Dose
      escalation was performed according to the modified continual reassessment method
      scale and resulted in four cohorts of patients: TMZ 150 mg/m2 5 days/week each 4
      weeks and PEG 0.5 microg/kg/week - TMZ 150 mg/m2 5 days/week and PEG 1.0
      microg/kg/week - TMZ 200 mg/m2 5 days/week and PEG 0.5 microg/kg/week - TMZ 200
      mg/m2 5 days/week and PEG 1.0 microg/kg/week. Patients received a maximum of six
      cycles. Thirty-three patients were enrolled in this study: one in the first dose
      level, one in the second one, 18 in the third one and 11 in the fourth one. At
      level 4, four of 11 patients experienced dose-limiting toxicity and four nondose
      limiting toxicity; toxicity was mainly hematologic (grade IV thrombocytopenia).
      An objective response was observed in five patients (two complete response and
      three partial response) receiving level 3 or 4 of treatment. The disease remained
      stable in three patients, and six of 31 patients were alive 24 months after
      enrollment. The association of oral TMZ with subcutaneous PEG in metastatic
      melanoma displayed an unacceptable hematological toxicity with the dosages of 200
      mg/m2 5 days/week and 1 microg/week, respectively. At a lower level, this
      treatment was effective and deserves further investigations to define its
      indications in metastatic melanoma patients.

PMID- 18337652
TI  - Phase II trial of arsenic trioxide and ascorbic acid with temozolomide in
      patients with metastatic melanoma with or without central nervous system
      metastases.
AB  - We conducted a single institution phase II trial to evaluate the tolerability and
      effectiveness of therapy with arsenic trioxide (ATO) and ascorbic acid (AA) with
      temozolomide (TMZ) in patients with advanced melanoma. Planned enrollment was for
      40 patients. Eligible patients were required to have metastatic melanoma with or
      without brain metastases, an ECOG performance status of 0-2, and adequate organ
      function. The primary endpoints were overall response rate and degree of grade 4
      toxicity. ATO was administered as a loading dose at 0.25 mg/kg/day for 5 days
      during week 0, and then twice weekly at 0.35 mg/kg during an 8-week cycle. Each
      infusion of ATO was followed by an infusion of 1000 mg of AA. TMZ was given at
      the standard dose of 200 mg/m for 5 days during weeks 1 and 5 of each cycle.
      Eleven patients were enrolled with 10 evaluable for response, five with central
      nervous system disease. No responses were seen among the first 10 patients and on
      the basis of a predetermined stopping rule, the trial was terminated. Common
      grade 1 and 2 side effects included nausea and vomiting (10), fatigue (six),
      edema (six), rash (six), and elevated AST or ALT (six). Grade 3 and 4 side
      effects included nausea and vomiting (three), elevated AST or ALT (two), seizure
      (one), and renal failure (one). This is the first trial combining ATO with
      chemotherapy in a solid tumor. ATO and AA were administered in the outpatient
      setting with TMZ in 11 patients with an acceptable side effect profile. No
      responses were seen in the first 10 evaluable patients leading to early closure
      of the study. Further studies using ATO and AA with TMZ with this dosing schedule
      in advanced melanoma are not warranted.

PMID- 18337653
TI  - Evidence-based and interdisciplinary consensus-based German guidelines: systemic
      medical treatment of melanoma in the adjuvant and palliative setting.
AB  - Systemic medical treatment of melanoma is administered in the adjuvant and
      palliative setting. Adjuvant therapy may be considered in patients with primary
      melanoma with more than 1.5 mm tumor thickness and with regional node metastasis.
      Presently no indication for systemic adjuvant chemotherapy or for adjuvant
      therapy with nonspecific immune-stimulatory agents outside controlled studies is
      seen. Interferon-alpha is the first substance in the adjuvant therapy of
      melanoma, which has shown to present a significant advantage to the patients in
      some prospective randomized studies. Good arguments for using adjuvant interferon
      alpha therapy in high-risk melanoma patients exist. Both high-dose and low-dose
      interferon-alpha show promise. The major indications for systemic chemotherapy
      and chemoimmunotherapy are inoperable recurrent tumors, inoperable regional
      metastases and distant metastases (stage IV). As treatment in such situations is
      primarily palliative, the effect of any regimen on the quality of life must be
      carefully weighed. As a first line treatment, single agent therapy is
      recommended, as polychemotherapy or biochemotherapy did not show significant
      advantages for prolongation of survival; hence they are more toxic. An urgent
      need for development of new treatment modalities is necessary and general
      principles of experimental immunotherapy are outlined.

PMID- 18337654
TI  - Dramatic reduction of chronic lymphoedema of the lower limb with sorafenib
      therapy.
AB  - This paper describes an interesting case report based on a patient who had a
      dramatic and astounding reduction in her chronic lymphoedema while on sorafenib.

PMID- 18337655
TI  - Influence of time of rejection on long-term graft survival in renal
      transplantation.
AB  - BACKGROUND: The aim of this analysis was to investigate the relationship of acute
      rejection episodes (ARE) at different times posttransplantation with
      reversibility of graft dysfunction and long-term graft failure using data from
      the Collaborative Transplant Study database. METHODS: A total of 28,867 patients
      receiving their graft between 1995 and 2005 from deceased donors were included in
      the analysis. The time from renal transplantation to first treated ARE was
      divided into intervals up to 3 years. Long-term graft survival and half-life
      rates were calculated and hazard ratios (HR) for failure were computed using
      multivariate Cox regression analysis. RESULTS: Compared with patients who did not
      receive rejection treatment during the first posttransplant year, HR for graft
      survival increased to 1.35 for patients with rejection 0 to 90 days (P<0.001),
      2.05 with rejection 91 to 180 days (P<0.001), and 2.74 with rejection 181 to 365
      days of posttransplantion (P<0.001). First rejections occurring during the second
      year were associated with HR 3.35 (P<0.001) and rejections during the third year
      with HR 3.17 (P<0.001). In addition to the time of rejection, the degree of
      functional recovery after rejection treatment was found to be important for
      subsequent graft survival. CONCLUSION: The time point of occurrence and the
      degree of functional recovery after rejection treatment were found to
      significantly influence the impact of ARE on long-term graft survival, and we
      were able to quantify the associated risks.

PMID- 18337656
TI  - Indirect allorecognition: not simple but effective.
AB  - Donor dendritic cells are potent but short-lived stimulators of early transplant
      rejection, and recipient antigen presenting cells presenting donor major
      histocompatibility complex peptides sustain immunoreactivity and contribute to
      chronic rejection. We briefly consider how CD4 T cells that recognize allopeptide
      can provide help for effector and regulatory responses and highlight the
      implications for promoting graft survival.

PMID- 18337657
TI  - Vitamin D deficiency in African American kidney transplant recipients: bringing a
      common problem to light.

PMID- 18337658
TI  - Paired kidney exchange: how far and how wide?

PMID- 18337659
TI  - Inhibition of ICAM-1/LFA-1 interactions prevents B-cell-dependent anti-CD45RB
      induced transplantation tolerance.
AB  - BACKGROUND: Allogeneic tolerance can be reliably obtained with monoclonal
      antibody therapy targeting CD45RB. Although regulatory T cells play an important
      role in the mechanism, we have recently demonstrated the active participation of
      host B lymphocytes. After anti-CD45RB therapy, B lymphocytes demonstrate
      phenotypic alterations that include up-regulation of CD54 (intercellular adhesion
      molecule [ICAM]-1). We have investigated the hypothesis that alteration in ICAM-1
      expression is required for tolerance induction. MATERIALS AND METHODS: Recipients
      of heterotopic allogeneic cardiac grafts (C3H donors into B6 recipients) were
      treated with anti-CD45RB, anti-ICAM, anti-lymphocyte function-associated antigen
      1 (LFA), or the combination of these agents. These data were extended by
      performing allogeneic cardiac transplants into ICAM or LFA recipients treated
      with a 5-day course of anti-CD45RB. Finally, B-cell-deficient animals were
      reconstituted with ICAM splenocytes to create a recipient with a selective
      deficiency of ICAM-1 restricted to the B-cell compartment. RESULTS: Anti-CD45RB
      alone or the combination of anti-LFA/anti-ICAM reliably induced transplantation
      tolerance. However, the triple combination was routinely unsuccessful and induced
      long-term graft survival in no recipients. ICAM-deficient or LFA-deficient
      recipients were also resistant to tolerance induced by anti-CD45RB. Finally,
      transfer of control splenocytes to B-cell-deficient recipients permitted anti
      CD45RB-induced tolerance, whereas transfer of ICAM cells was unable to support
      tolerance induction. CONCLUSIONS: Expression of ICAM-1 by B lymphocytes and
      interaction with LFA-1 form a central aspect of transplantation tolerance induced
      by anti-CD45RB therapy. These data further elucidate the cellular mechanisms used
      by B lymphocytes in the induction of transplantation tolerance.

PMID- 18337660
TI  - Adult living-donor liver transplantation with ABO-incompatible grafts.
AB  - BACKGROUND: Liver transplantation using ABO-incompatible grafts is rarely
      performed because the reported outcome is poorer than with compatible grafts. We
      report our positive experience with adult-to-adult living-donor liver transplant
      (LDLT) using ABO-incompatible grafts. METHODS: The immunosuppressive protocol
      consisted of plasmapheresis/intravenous immunoglobulin infusion before LDLT
      followed by thymoglobulin induction and splenectomy, maintenance with
      tacrolimus/cyclosporine (FK/CSA), mycophenolate mofetil, and a rapid steroid
      taper. Plasmapheresis was planned for up to 3 months after LDLT aiming at
      maintaining the anti-ABO titers level below 1:16. Liver biopsies were routinely
      stained for humoral rejection with complement 4d (C4d) and for biliary damage
      with cytokeratin 7. RESULTS: Between January 2003 and September 2004, five
      patients, mean age 59 years, received an ABO-incompatible LDLT. Patient and graft
      survival was 80% at mean follow-up of 43 months (range, 34-54) for the four
      surviving patients. One patient died 4 months after LDLT. Humoral rejection
      occurred in one patient whereas acute cellular rejection was diagnosed in four
      patients. CONCLUSIONS: ABO-incompatible LDLT can be performed with patient and
      graft survival similar to compatible LDLT. Minimization of immunosuppression is
      possible, and chronic biliary damage is not the norm. Better tools than
      complement 4d staining must be researched to diagnose the features of immunologic
      damage to the graft. If these results will be confirmed in a greater number of
      patients, ABO-incompatible LDLT may be proposed when ABO-compatible donors are
      not available or when the ABO-incompatible donor is the better candidate.

PMID- 18337661
TI  - A model for human leukocyte antigen-matched donor-swap transplantation in India.
AB  - BACKGROUND: In developing countries such as India, extending donor-swap
      transplantation (DSTx) to human leukocyte antigen (HLA)-mismatched patient-donor
      pairs would increase well-matched living donor kidney transplantation rates,
      resulting in use of less immunosuppression and less expenses, lower infective
      morbidity, and better survival. A model for DSTx based on HLA matching is
      presented. METHODS: Consecutive HLA class 1 antigen (A, B) tests of prospective
      renal allograft recipients and their related donors, performed at a single center
      in India was analyzed retrospectively using an HLA matching program to determine
      the proportion of prospective recipients with poorly matched related donors who
      could have benefited by DSTx based on HLA matching. RESULTS: Over the past 17.5
      years, 2,129 prospective renal allograft recipients and 2,890 donors were tested
      for HLA class I (A and B) antigens. Of the prospective recipients, 33% did not
      have well-matched donors (defined as blood group compatible and sharing > or =2
      of 4 HLA class I antigens). Among such recipients, 19.2% could have found a well
      matched donor-swap pair within a year at a single center. This number would
      increase to 38% if four major national centers were involved with a shared HLA
      registry. CONCLUSIONS: Nearly 40% of prospective recipients without well-matched
      donors would find a donor-swap pair based on HLA matching within a year, with
      coordination among four national centers and a shared HLA registry, increasing
      the well-matched living donor renal transplant rates and improving transplant
      outcomes. This finding is relevant in the context of Indian government amending
      the Transplantation of Human Organs Act to encourage DSTx.

PMID- 18337662
TI  - Intragraft coagulation events and delayed graft function in clinical renal
      transplantation.
AB  - BACKGROUND: Cold preservation, reperfusion damage, immunosuppressive drugs, and
      uremia-induced acquired thrombophilias increase the risk of thrombotic
      complications in renal transplantation. Intragraft fibrin deposition may be
      associated with delayed graft function. METHODS: We studied coagulation and
      fibrinolysis in 45 patients of a larger trial in renal transplantation:
      perioperative antithymocyte globulin (group A, n=15), perioperative basiliximab
      (group B, n=16), and conventional triple therapy (group C, n=14). Blood samples
      for prothrombin fragment F1+2, plasminogen activator inhibitor (PAI)-1, d-dimer,
      tPA antigen, tPA activity, and platelet counts were obtained simultaneously at 1
      and 5 min after reperfusion from iliac artery and graft vein for calculation of
      transrenal changes. Because antithymocyte globulin activates coagulation and
      fibrinolysis, group A was analyzed separately. Groups B and C were pooled (group
      BC). RESULTS: In group BC, transrenal D-dimer release occurred at 1 min, tPA
      antigen release at 1 and 5 min, and transrenal PAI-1 uptake at 5 min
      postreperfusion. tPA activity increased marginally only at 1 min. High graft tPA
      antigen release at 5 min and D-dimer release at 1 min were associated with
      delayed graft function. In group A, transrenal tPA-antigen release occurred at 1
      and 5 min and D-dimer release at 1 min. There were no transrenal F1+2 changes in
      either group. CONCLUSION: Although graft PAI-1 uptake inhibits tPA activity,
      graft releases D-dimer at early reperfusion without concomitant F1+2 release.
      Data suggest thrombin and fibrin formation already before cold preservation
      during donor care and organ retrieval. This fibrin deposition increases risk of
      delayed graft function.

PMID- 18337663
TI  - Q-methodology to identify young adult renal transplant recipients at risk for
      nonadherence.
AB  - BACKGROUND: Young adult renal transplant recipients may display patterns of
      behavior that affect graft survival. The present study aimed to identify young
      adults at risk for nonadherent behavior by investigating their attitudes about
      posttransplant health lifestyle. METHOD: A Q-methodological study was conducted.
      Participants were asked to rank-order statements on issues potentially associated
      with (non)adherence. Factor analysis was applied to uncover patterns in the
      ranking of statements. The resulting factors represent attitudes and are
      described using a composite ranking of the statements. As a first test of
      discriminated validity, a different group of 34 young renal transplant patients
      was asked how well the factor descriptions fitted them. RESULTS: Twenty-six young
      renal transplant recipients (18-25 years) participated in the study. They were
      remarkably willing to discuss sensitive issues when confronted with statements on
      cards. Four distinct attitude profiles concerning posttransplant health lifestyle
      were found among these young adults: (a) concerned and controlled, (b) appearance
      orientated, (c) opinionated and independent, and (d) easy going and pliable. In a
      follow-up analysis, self-categorization proved to discriminate well between the
      four attitude profiles in 67% of the respondents. CONCLUSIONS: Using Q
      methodology, four attitude profiles about posttransplant health lifestyle were
      uncovered. Self-categorization on these attitudes seems feasible and may be a
      useful screening aid to identify young adults at risk for nonadherence.

PMID- 18337664
TI  - Clinical usefulness of FDG-PET/CT scan imaging in the management of
      posttransplant lymphoproliferative disease.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is, aside skin
      cancer, the most common malignancy occurring after solid organ transplant in
      adults. Fluorodeoxyglucose (FDG) positron emission tomography (PET) has proved
      useful in the management of lymphomas. METHODS: We report our experience with the
      use of FDG-PET inline with computed tomography (CT) scanning in the management of
      four transplant recipients with histologically confirmed PTLD, including three
      monomorphic PTLDs and one polymorphic PTLD. RESULTS: FDG-PET/CT scan at diagnosis
      showed increased FDG uptake in all examined PTLD lesions, and the disease was
      upstaged on the basis of FDG-PET/CT scan results over conventional CT scanning in
      one patient. At the end of treatment, PET/CT scans no longer demonstrated FDG
      uptake in the original PTLD lesions in all patients. Complete remission of
      disease persisted for at least 1 year after diagnosis in all. CONCLUSIONS: Our
      results strongly support that FDG-PET scanning is highly specific for diagnosis
      and follow-up of PTLD. The clinical relevance of including FDG-PET/CT scanning in
      the management of PTLD should be evaluated in a larger prospective cohort study.

PMID- 18337665
TI  - Simultaneous or sequential combined living donor-intestine transplantation in
      children.
AB  - BACKGROUND: Since the report of the first successful living donor combined liver
      intestine transplant in pediatric patients, three other cases have been
      performed. In this article, we describe surgical technique, outcome, and propose
      a broader application of this procedure using deceased donors. PATIENTS: Four
      children of mean age 15.5 months (11-24 months) and weight 9.5 kg (8-10.9 kg)
      affected by end-stage liver and intestinal failure underwent living donor
      combined liver-intestine transplant with a left lateral liver and a distal
      segment of jejunum. In one case, the organs were transplanted simultaneously and
      in three in staged procedures. In all cases the liver transplant was performed
      first. The intestine was always transplanted with systemic venous drainage. The
      biliary anastomosis was a duct-to-duct, a biliodigestive, or a combined one
      according to the biliary anatomy of the liver graft. The abdomen was routinely
      closed with a Vicryl mesh followed by a skin graft. A loop graft ileostomy was
      fashioned for protocol biopsies and taken down within 3 months. RESULTS: One
      intestine was lost to generalized ischemia. The child was promptly retransplanted
      with another living donor graft. All children are alive and well at an average
      follow-up of 30 months (18-54 months). CONCLUSIONS: Living donor combined liver
      intestine transplant can be performed successfully with excellent early outcome.
      The in situ splitting technique here described can be applied to obtain grafts
      for small children from appropriate adult deceased donors.

PMID- 18337666
TI  - Intrahepatic complement activation, sinusoidal endothelial injury, and lactic
      acidosis are associated with initial poor function of the liver after
      transplantation.
AB  - BACKGROUND: Changes in glucose metabolism in the liver during transplantation
      have been recently described using microdialysis. Here, these findings are
      correlated with histopathologic, immunohistochemical, and ultrastructural changes
      in liver. METHODS: Microdialysis catheters were inserted into 15 human livers,
      which were perfused with isotonic solution, and samples of perfusate were
      analyzed before harvest, after storage, and after reperfusion. At each stage
      Menghini needle biopsy samples were taken and each studied using light and
      electron microscopy. RESULTS: Six livers showed serum biochemical evidence of
      initial poor function. These livers had significantly more staining for
      complement fragment 4d (C4d) of both lobular and periportal hepatocytes. C4d
      positive hepatocytes were also found in the liver during cold storage (3 of 15).
      These periportal hepatocytes also showed evidence of necrosis and were found to
      have intracellular neutrophils. Hepatocyte rounding in zone III, necrosis, and
      C4d staining in recipient were also significantly correlated with the degree of
      lactic acidosis during this phase. Intrahepatic lactic acidosis at all time
      points was significantly associated with sinusoidal endothelial cell injury after
      reperfusion. There were no correlations between glucose, pyruvate, and glycerol
      levels and histopathologic changes in the liver. DISCUSSION: In the patients
      studied, the degree of C4d staining correlated with initial poor function and was
      associated with intrahepatic lactic acidosis in the donor during cold storage and
      after reperfusion. Complement activity in the liver during cold storage may be
      after in situ activation. Intrahepatic lactic acidosis is associated with
      sinusoidal endothelial cell and hepatocyte injury. The role of intrahepatic
      neutrophils is uncertain and could possibly be in response to cell necrosis.

PMID- 18337667
TI  - Attenuation of airway obliteration by ciprofloxacin in experimental
      posttransplant bronchiolitis obliterans.
AB  - BACKGROUND: Ciprofloxacin is widely used to treat respiratory tract infections.
      Like other fluoroquinolones, ciprofloxacin has immunomodulatory effects; however,
      it is unknown whether these effects are beneficial in the setting of lung
      transplantation. We investigated potential immunomodulatory effects of
      ciprofloxacin in a model of posttransplant bronchiolitis obliterans. METHODS: The
      heterotopic tracheal transplantation model in rats was used. Three groups
      received ciprofloxacin and underwent different immunosuppressive regimens of
      cyclosporine A, that is, no immunosuppression, insufficient immunosuppression, or
      low-dose immunosuppression. Three groups underwent the same immunosuppressive
      regimen but had no ciprofloxacin treatment. Tracheas were harvested after 21 days
      and examined with respect to histology and expression of selected cytokines.
      RESULTS: The allografts of animals treated with ciprofloxacin showed less airway
      obliteration compared with allografts of untreated animals. When combined with
      low-dose immunosuppression ciprofloxacin showed beneficial effects in preventing
      airway obliteration and rejection of the respiratory epithelium. Cytokine gene
      expression of the allografts treated with ciprofloxacin was higher with respect
      to transforming growth factor-beta and equal with respect to tumor necrosis
      factor-alpha and interferon-gamma compared with controls. When applied in
      combination with cyclosporine A, ciprofloxacin lowered the expression of
      transforming growth factor-beta and tumor necrosis factor-alpha and increased
      interferon-gamma expression. CONCLUSION: Ciprofloxacin attenuates airway
      rejection after tracheal transplantation. Genetic expression of mediators that
      are known to play an important role in mediating rejection in this model supports
      an immunomodulatory and antifibrotic role of ciprofloxacin. These findings
      suggest that further clinical studies are needed to investigate whether
      ciprofloxacin in addition to its bactericidal effect might be beneficial in the
      treatment of human posttransplant bronchiolitis obliterans.

PMID- 18337668
TI  - Pharmacological preconditioning with simvastatin protects liver from ischemia
      reperfusion injury by heme oxygenase-1 induction.
AB  - BACKGROUND: The protective role of heme oxygenase-1 (HO-1) against liver ischemia
      reperfusion (I/R) injury in models of hypoxic and remote preconditioning has been
      proved. The feasible candidates who induce HO-1 and thorough which exert the
      protective effects are under investigation. The aim was to study the role of HO-1
      in pharmacological preconditioning by simvastatin in a rat model. METHODS:
      Pharmacological preconditioning by intraperitoneal injection of simvastatin (5
      mg/kg) was tested on a partial liver I/R model on rats. The expression of HO-1
      protein and enzyme activities in livers, serum alanine transaminase (ALT) levels,
      and TUNEL staining of liver after I/R injury were measured in rats with and
      without simvastatin preconditioning. RESULTS: HO-1 was induced and persistently
      overexpressed in the hepatocytes 24 hr after simvastatin treatment. Simvastatin
      preconditioning diminished the elevation of serum ALT levels 4 hr after I/R
      injury (69.6+/-26.3 U/L) (P<0.05 vs. other groups) when compared with control
      (403.8+/-261.9 U/L) and zinc protoporphyrin (ZnPP)-pretreated (717.5+/-205.6 U/L)
      groups. Simvastatin preconditioning diminished the apoptosis after I/R injury as
      well (apoptosis index: 26.4+/-8 for Simvastatin, 78+/-7 for control, and 85.3+/-2
      for ZnPP group; P<0.05). The addition of ZnPP negated the protective effects of
      simvastatin as evidenced in the ALT level (406.2+/-243.0 U/L) and apoptosis index
      (75.6+/-6). The heme oxygenase activity in treated rats correlated with these
      results. CONCLUSIONS: The induction of HO-1 by simvastatin preconditioning played
      a protective role against hepatic I/R injury.

PMID- 18337669
TI  - Effect of the antioxidant idebenone on adverse events under mycophenolate mofetil
      therapy in a rat model.
AB  - BACKGROUND: Diarrhea and anemia are side effects of mycophenolic acid (MPA), but
      underlying mechanisms are not fully understood. Gene expression of major-alpha
      hemoglobin and catalase was suppressed in livers of mycophenolate mofetil (MMF)
      treated rats, suggesting MPA attenuates cellular defense against reactive oxygen
      species (ROS). We investigated whether the antioxidant idebenone might alleviate
      MPA-related side effects. METHODS: Rats were treated as follows: group 1:
      controls; group 2: idebenone; group 3: MMF; and group 4: MMF/idebenone. Blood was
      collected weekly to determine cell counts, hemoglobin, MPA, plasma albumin, total
      protein, creatinine, and urea concentrations. On day 28 RNA was extracted from
      liver, kidneys, and bone marrow (BM). Colon and jejunum were examined
      histologically. RESULTS: High-dose MMF-treated rats developed diarrhea,
      dehydration, and weight loss. After a week, a significant decrease (P=0.001) in
      erythrocyte count and hemoglobin concentration was observed that was not
      influenced by idebenone. Degenerative changes in the jejunum were slightly
      attenuated by idebenone. Idebenone did not influence MPA-induced suppression of
      catalase. A significant suppression of major-alpha-hemoglobin and the
      erythropoietin (EPO)-receptor in BM of MMF-treated groups and almost complete
      absence of hemopoietic progenitor cells were observed. EPO-mRNA was markedly
      upregulated in the MMF-group and even more in the MMF/idebenone-group.
      CONCLUSION: Idebenone showed minimal benefit on MMF-related diarrhea and anemia.
      BM of MMF-treated rats revealed erythroid aplasia as a possible reason for
      anemia. Marked upregulation of EPO-mRNA presumably reflects a compensatory
      mechanism. Because ROS have the potential to suppress EPO expression, it can be
      hypothesized that enhanced EPO-mRNA expression in MMF/idebenone-treated rats is
      caused by antagonism of ROS.

PMID- 18337670
TI  - Recovery of liver perfusion after focal outflow obstruction and liver resection.
AB  - BACKGROUND: Live liver donation requires extended liver resection in the donor
      with transection of the middle hepatic vein. This leads to focal outflow
      obstruction in the remnant liver or the partial graft. This study was designed to
      characterize the pathophysiological correlate of focal outflow obstruction in a
      small-for-size liver and its course of recovery in a rat model. METHODS: Ligation
      of the right median hepatic vein was combined with 50% hepatectomy.
      Microcirculation was visualized by orthogonal polarization spectroscopy after
      each operative step and before killing on days 1, 2, and 7. Histologic evaluation
      included morphological assessment, immunohistochemical determination of
      proliferation using BrdU, and laminin and von Willebrand factor expression, which
      both indicate vascularization of sinusoids. RESULTS: After ligation of the right
      median hepatic vein, congestion was visible and no sinusoidal blood flow was
      detected in the obstruction zone. By day 1 confluent centrilobular necrosis
      developed. Sinusoidal perfusion in the obstruction zone recovered partially. Many
      dilated vascularized sinusoidal canals connecting the obstruction zone with the
      normal zone were visible. Proliferative activity in the obstruction zone was
      markedly reduced compared with the normal zone. By day 7, liver parenchyma in the
      obstruction zone looked normal as did sinusoidal perfusion. In the border zone,
      few dilated vascular canals were apparent. CONCLUSION: Confluent centrilobular
      necrosis in the early postoperative phase, resulting from focal outflow
      obstruction, may be crucial for the development of a small-for-size syndrome. The
      exclusion of the outflow-obstructed zone from the functional liver mass during
      preoperative radiological risk assessment seems to be the logical consequence.
      Recovery of focal outflow obstruction occurs spontaneously by means of dilated
      sinusoids in the border zone, forming vascularized sinusoidal canals, which could
      serve as intrahepatic anastomosis.

PMID- 18337671
TI  - Impact of psoralen/UVA-treatment on survival, activation, and immunostimulatory
      capacity of monocyte-derived dendritic cells.
AB  - BACKGROUND: Extracorporeal Photopheresis (ECP) has been shown to be an effective
      treatment of graft-versus-host disease, solid organ graft rejection, and other T
      cell-mediated diseases. The mechanisms of action of ECP include lymphocyte
      apoptosis, cytokine modulation, and the induction of regulatory T cells. It has
      been suggested that dendritic cells (DCs) are more resistant to ECP-induced
      apoptosis and might be directly modulated by ECP. We tested this hypothesis using
      in vitro Psoralen/UVA (PUVA) treatment as an in vitro model of ECP. METHODS:
      Monocyte-derived DCs (mo-DCs) were treated with 8-methoxypsoralen /UVA and
      analyzed for surface molecule expression, apoptosis markers, endocytosis, and
      migratory and immunostimulatory capacity. Mo-DC phenotype and cytokine secretion
      was tested after CD40L stimulation. Naive T cells stimulated with PUVA-treated mo
      DCs were tested for Th1/Th2 cytokine secretion and associated chemokine receptor
      patterns. RESULTS: DCs underwent apoptosis after in vitro PUVA and in vivo ECP.
      In vitro, the induction of apoptosis was preceded by partial maturation of
      immature mo-DCs. PUVA-treated immature mo-DCs also exhibited enhanced migratory
      and immunostimulatory capacity. However, mo-DCs stimulation through CD40 ligation
      was abrogated and interleukin (IL)-12 secretion was abolished 24 hr after PUVA
      treatment. PUVA-treated mo-DCs skewed naive T cells toward a Th2 response as
      defined by increased IL-4, IL-10, and IL-13 and decreased interferon-gamma
      levels, and the expression of the Th2-associated chemokine receptors CCR4 and
      CCR10. The observed Th2 shift was partially reversed by exogenous IL-12.
      CONCLUSION: These data suggest that direct modulation of DC function as well as
      apoptosis contribute to the immunoregulatory effects of ECP.

PMID- 18337672
TI  - High prevalence of vitamin D deficiency in African American kidney transplant
      recipients.
AB  - Kidney transplant patients are at high risk for developing Vitamin D(3)
      deficiency. The prevalence rates of 25(OH) Vitamin D(3) deficiency and its
      association with parathyroid hormone (PTH) levels in African American kidney
      transplant recipients have not been examined. We measured 25(OH) Vitamin D(3) and
      intact PTH concentrations in 38 African American transplant patients at our
      center in October 2006. We collected various laboratory data including serum
      creatinine, calcium, phosphate, alkaline phosphatase, and glomerular filtration
      rate. Vitamin D(3) deficiency was present in 57.8% of the patients and 94.7% had
      insufficiency. Ten of 22 (45%) patients with chronic kidney disease stage 3 had
      intact PTH more than or equal to 70 pg/mL. On multivariate analysis, 25(OH)
      Vitamin D(3) level was negatively correlated with intact PTH (P<0.01) and
      alkaline phosphatase level was positively associated with intact PTH levels
      (P<0.002). Vitamin D(3) deficiency and insufficiency is present in most of the
      African American kidney transplant patients.

PMID- 18337673
TI  - Pseudomonas aeruginosa colonization of the allograft after lung transplantation
      and the risk of bronchiolitis obliterans syndrome.
AB  - Long-term survival after lung transplantation remains limited by the development
      of bronchiolitis obliterans syndrome (BOS). Allograft colonization with
      Pseudomonas aeruginosa is common particularly in recipients with BOS, but a
      possible etiological relationship remains unexplored. In 155 consecutive lung
      transplants, the development of allograft colonization with Pseudomonas was
      strongly associated with the development of BOS within 2 years of transplant
      (23.4% vs. 7.7% in those colonized and not colonized, respectively, P=0.006).
      Freedom from BOS was significantly shorter in those patients without any
      pretransplant bacterial reservoir developing de novo allograft pseudomonal
      colonization as compared with those remaining free of colonization (Kaplan-Meier
      log-rank P=0.014). The isolation of Pseudomonas preceded the diagnosis of BOS in
      14 of 18 (78%) and by a median of 204 days (95% confidence interval 115-492) in
      patients developing both these complications. We conclude that de novo
      colonization of the lung allograft by Pseudomonas is strongly associated with the
      subsequent development of BOS.

PMID- 18337674
TI  - Adult right lobe live donor liver transplantation without reconstruction of the
      middle hepatic vein: a single-center study of 109 cases.
AB  - We report our experience in adult-to-adult right hepatic lobe living donor liver
      transplantation (ALDLT) using extension of the hepatectomy transection line
      medially to incorporate the right middle hepatic vein branches into the donor
      graft. One hundred and nine ALDLT were performed at the University of Colorado
      from August 1997 to December 2005. Donors were screened preoperatively for
      hepatic venous anatomy compatible with this technique. Of the 109 ALDLT, the
      first 10 did not include the right middle hepatic vein branches in the graft. As
      such, three patients required retransplantation, two from graft loss because of
      venous congestion. Of the next 99 transplants, only 11 required retransplantation
      and none because of venous congestion. This approach allows adequate venous
      outflow through the right hepatic vein more than 1 cm, which is demonstrated by
      the absence of graft loss from venous congestion and superior graft survival.

PMID- 18337675
TI  - Rescue of acute complete portal vein occlusion with Doppler ultrasound findings
      after liver transplantation.

PMID- 18337676
TI  - Successful treatment of subcutaneous Scytalidium hyalinum infection with
      voriconazole and topical terbinafine in a cardiac transplant patient.

PMID- 18337677
TI  - Aortic medial degeneration in a liver transplant donor: a case report.

PMID- 18337683
TI  - Temporal profile of fluorodeoxyglucose uptake in malignant lesions and normal
      organs over extended time periods in patients with lung carcinoma: implications
      for its utilization in assessing malignant lesions.
AB  - AIM: In this study, the fluorodeoxyglucose (FDG) uptake was prospectively
      investigated in tumors as well as the normal organs over 8 h in patients with non
      small cell lung carcinoma (NSCLC). The intent of this study was to collect
      positron emission tomography (PET) data with regard to the time course of FDG
      uptake in the primary and metastatic sites and the normal tissues over extended
      time periods (up to 8 h) after intravenous FDG injection in patients. METHODS:
      Three patients (2 males, 1 female; mean age: 64 years; age range: 57-76 years)
      with the diagnosis of NSCLC underwent a series of whole body FDG-PET at several
      time points, beginning at 5 min and extending up to 8 h after the intravenous
      administration of FDG. We calculated the standardized uptake values (SUVmax) in
      the malignant lesions and all organs. SUVmax was calculated over contiguous
      slices and the highest value was considered for the analysis. Similar locations
      were used for the placement of regions of interest in subsequent images. Time
      activity curves (TACs) were generated utilizing these SUV values for each of
      these sites. The ratios of the SUVmax of the malignant lesions to those of normal
      organs (viz. lung and liver) at specific time points were also calculated and the
      TACs for these ratios were generated. The blood and plasma decay curves of (18)F
      activity over time were generated based on the counts obtained from blood sample
      analysis. The ratios of 18F activity of blood to plasma were also calculated and
      the TACs of this ratio were generated. RESULTS: The observed mean SUVmax at
      different time points (5 min, 1 h, 2 h, 4 h, 6 h and 8 h) in the organs and the
      lesions were as follows: 1) heart: 2.9, 2, 1.9, 1.6, 1.3, 1.5; 2) kidney: 3.3,
      3.5, 2.6, 2.1, 2, 2; 3) liver: 3.9, 2.2, 1.9, 1.6, 1.5, 1.8; 4) lung: 0.6, 0.5,
      0.4, 0.4, 0.4, 0.4, 0.4; 5) large bowel: 2.1, 1.4, 1.8, 1.4, 2, 2.2; 6) small
      bowel: 2.6, 1.6, 1.4, 1.2, 1.3, 1.5; 7) lung neoplasm: 3.7, 5.1, 6.1, 6.8, 6.9,
      6.8; 8) mediastinal lesion 1: 6.8, 8.8, 13, 12.7, 13.8, 12.5; 9) mediastinal
      lesion 2: 5.5, 8.6, 10.7, 13.2, 11.7, 12.1; 10) adrenal metastasis (starting at 1
      h): 3.3, 3.7, 4.7, 4.7, 4.7; 11) right iliac metastasis: 2.6, 2.6, 3.1, 3.5, 3.4.
      For the right iliac metastasis, we had SUVmax up to 6 h. The SUVmax ratios of
      malignant lesions to those of normal lung and liver and their TACs demonstrate
      initial rise followed by a delayed plateau. Increasing (18)F count ratios of
      blood to plasma with time was observed in 2 patients where these data were
      available. CONCLUSIONS: The results from this preliminary study indicate that
      while the tumor sites show increased uptake of FDG during the course of 8 h,
      surrounding normal tissues demonstrate declining or stable values with time. This
      would indicate increasing contrast between the lesion and the background and,
      therefore, possibly improved sensitivity of the test. While the high SUV at 5 min
      can be explained by the blood pool activity in the organs and the malignant
      lesions, the SUVmax values at the later times decreases or remains the same in
      normal organs. The observation on the different slopes of the curves among the
      various malignant lesions can be partly explained by the well known ''seed and
      soil'' theory in cancer biology. The finding of continued increases in the blood
      to plasma count ratios of (18)F activity is also noteworthy and most likely
      reflects GLUT-1 mediated glucose transport into red blood cells.

PMID- 18337684
TI  - Feasibility of the sentinel node biopsy in anal cancer.
AB  - AIM: Anal cancer is a rare neoplasm. According to a European Organization for
      Research and Treatment of Cancer multivariate analysis, synchronous inguinal
      lymph node metastasis occurs in 10-25% of patients and constitutes an independent
      prognostic factor for local failure and overall mortality. METHODS: Inguinal
      lymph node status was assessed using the sentinel node technique in 35 patients
      with anal cancer. RESULTS: Histology revealed 23 squamous carcinomas, 10 basaloid
      carcinomas, 1 squamous carcinoma with basaloid areas and 1 spinocellular
      epithelioma associated with areas of Bowen's disease. Disease stage was T1 in 5
      patients, T2 in 18, T3 in 11 and T4 in 1 patient. Lympho-scintigraphy using a GE
      Millennium gamma camera was performed after peritumoral injection of 37 MBq of
      99mTc colloid. Surgical sentinel node biopsy with a portable Scintiprobe MR 100
      (Politech, Carsoli, Italy) had a detection rate of 97.1%. Inguinal metastases
      were detected in 7 (20%) patients, in 2 of which metastasis was bilateral.
      CONCLUSIONS: Given the correlation between prognosis and node involvement,
      sentinel node biopsy can be considered a simple method for adequate pretreatment
      staging of anal carcinoma. Use of the technique could avert the need for
      prophylactic inguinal radiotherapy in N0-N1 patients, thus reducing the morbidity
      associated with inguinal radiotherapy. Consistent follow-up is required to
      evaluate long-term results:

PMID- 18337685
TI  - The use of the rare UUA codon to define "expression space" for genes involved in
      secondary metabolism, development and environmental adaptation in streptomyces.
AB  - In Streptomyces coelicolor, bldA encodes the only tRNA for a rare leucine codon,
      UUA. This tRNA is unnecessary for growth, but is required for some aspects of
      secondary metabolism and morphological development, as revealed by the phenotypes
      of bldA mutants in diverse streptomycetes. This article is a comprehensive review
      of out understanding of this unusual situation. Based on information from four
      sequenced genomes it now appears that, typically, about 2 approximately 3% of
      genes in any one streptomycete contain a TTA codon, most having been acquired
      through species-specific horizontal gene transfer. Among the few widely conserved
      TTA-containing genes, mutations in just one, the pleiotropic regulatory gene
      adpA, give an obvious phenotype: such mutants are defective in aerial growth and
      sporulation, but vary in the extent of their impairment in secondary metabolism
      in different streptomycetes. The TTA codon in adpA is largely responsible for the
      morphological phenotype of a bldA mutant of S. coelicolor. AdpA-dependent targets
      include several genes involved in the integrated action of extracellular
      proteases that, at least in some species, are involved in the conversion of
      primary biomass into spores. The effects of bldA mutations on secondary
      metabolism are mostly attributable to the presence of TTA codons in pathway
      specific genes, particularly in transcriptional activator genes. This is not
      confined to S. coelicolor-it is true for about half of all known antibiotic
      biosynthetic gene sets from streptomycetes. Combined microarray and proteomic
      analysis of liquid (and therefore non-sporulating) S. coelicolor bldA mutant
      cultures revealed effects of the mutation during rapid growth, during transition
      phase, and in stationary phase. Some of these effects may be secondary
      consequences of changes in the pattern of ppGpp accumulation. It is argued that
      the preferential accumulation of the bldA tRNA under conditions in which growth
      is significantly constrained has evolved to favour the expression of genes that
      confer adaptive benefits in intermittently encountered sub-optimal environments.
      The evolution of this system may have been a secondary consequence of the
      selective pressure exerted by bacteriophage attack. Some biotechnological
      implications of bldA phenomenology are considered.

PMID- 18337686
TI  - Denaturing gradient gel electrophoresis analysis of bacterial community profiles
      in the rhizosphere of cry1AC-carrying Brassica rapa subsp. pekinensis.
AB  - The effect of genetically modified (GM) Brassica rapa subsp. pekinensis (Chinese
      cabbage) expressing Bt toxin gene (cry1AC) to the rhizosphere bacterial community
      was examined using the denaturing gradient gel electrophoresis (DGGE)
      fingerprinting method. From the visual comparison of the DGGE profiles, there
      were no significant differences between the profiles of Bt and control
      rhizosphere in both Suwon and Yesan samples. From the sequence analysis of the
      individual bands, Sphingomonas sp. of Alphaproteobacteria and several
      actinobacterial members were identified as the main bacterial taxa in both Suwon
      and Yesan samples. In the multiple correspondence analysis, no clear separation
      between Bt and control rhizosphere was seen in both Suwon and Yesan datasets. The
      profiles of bulk soils were separated from those of rhizosphere. The DGGE
      fingerprinting analyses indicated that Bt crops did not significantly alter the
      genetic composition of rhizosphere bacterial communities.

PMID- 18337687
TI  - Diversity and metal tolerance of nematode-trapping fungi in Pb-polluted soils.
AB  - The diversity of nematode-trapping fungi (NTF) in two lead (Pb) mines in Yunnan
      Province, China was investigated in 2004. In total, 20 species belonging to five
      genera were identified from 500 samples collected at the Lanping and the Huize
      mines. Pb concentrations ranged from 216 approximately 7,150 mg/kg for the former
      and 132 approximately 13,380 mg/kg for the latter, respectively. The fungi were
      divided into five groups based on different trapping mechanisms. The trapping-net
      producer group contained the largest number of species, with nine. Two predators,
      Dactylellina ellipsosporum and Arthrobotrys oligospora, were found at frequencies
      of 32.85% and 15.41%, respectively. The diversity indexes of NTF were positively
      correlated with Pb pollution levels in both the Lanping Mine (r=0.66) and the
      Huize Mine (r=0.72), suggesting that the distribution of NTF was not negatively
      affected by Pb contamination. For most strains of a given species, there was no
      significant difference (P>0.01) in the Pb tolerance between the strains isolated
      from habitats with low or high Pb concentrations. However, Pb toxicity exerted
      adverse effects on trap formation and predacious capability of fungi. We discuss
      the possible metal tolerance mechanisms and their relationships to the survival
      strategy of NTF in Pb-polluted environments.

PMID- 18337688
TI  - Removal of heavy metals by an enriched consortium.
AB  - An enriched consortium obtained from lake-sediment was developed for the removal
      of heavy metals such as Cu, Pb, Cr, Ni, and Zn from heavy metal-contaminated
      water. The removal efficiency of heavy metals in a shaking condition was
      generally higher than that in the static state. After the fifteenth enrichment
      with assorted heavy metals, the removal efficiencies in the shaking and static
      condition at an average concentration of 100 mg/L of each heavy metal were
      approximately 99 approximately 100% and 95 approximately 100%, respectively,
      depending on the type of heavy metal. An aerobically grown, pure culture isolated
      from an enriched culture was analyzed by 16S rRNA sequencing and identified as
      Ralstonia sp. HM-1. This strain was found to remove various heavy metals with an
      efficiency of approximately 97 approximately 100% at an average concentration of
      200 mg/L of each heavy metal.

PMID- 18337689
TI  - Genetic variation and geographic distribution of megalocytiviruses.
AB  - Viruses belonging to the genus Megalocytivirus in the family Iridoviridae have
      caused mass mortalities in marine and freshwater fish in Asian countries. In this
      study, partial major capsid protein (MCP) gene of seven Japanese and six Korean
      megalocytiviruses was sequenced and compared with the known megalocytiviruses to
      evaluate genetic variation and geographic distribution of the viruses. Comparison
      of MCP gene nucleotide sequences revealed sequence identity of 92.8% or greater
      among these 48 isolates. A phylogenetic tree clearly revealed three clusters:
      genotype I including nine Japanese isolates, thirteen Korean isolates, one
      Chinese isolates, one Thailand isolate and one South China Sea isolate; genotype
      II including five freshwater fish isolates in Southeast Asian countries and
      Australia; and the remaining genotype III mainly consisted of flatfish isolate in
      Korea and China. This suggests that viruses belonging to the genotype I widely
      distribute among various fish species in many Asian countries. Conversely, the
      epidemic viruses belonged to genotype II and III are may be still locally
      spreading and constrained in their prevalence to the limited host fish species,
      i.e., genotype II viruses mainly distribute in Southeast Asian countries, whereas
      genotype III viruses distribute in flatfish species in Korea and China.

PMID- 18337690
TI  - A novel archaeal group in the phylum Crenarchaeota found unexpectedly in an
      eukaryotic survey in the Cariaco Basin.
AB  - Archaea have been found in many more diverse habitats than previously believed
      due in part to modern molecular approaches to discovering microbial diversity. We
      report here an unexpected expansion of the habitat diversity of the Archaea in
      the Cariaco Basin we found using a primer set designed for 18S eukaryotic rDNA
      sequence analysis. The results presented here expand the originally identified 9
      archaeal clones reported in this environment using bacterial/archaeal primers to
      152 archaeal clones: 67 (18 OTU) of these clones were found at a depth of 900 m
      of station A while 71 (9 OTU) of them were at a depth of between 300
      approximately 335 m of station B&C depending upon which location the samples were
      taken. We used three phylogenetic analysis methods and detected 20 phylotypes
      belonging to a single previously unreported group distantly related to the
      Crenarchaeota. Also, we determined that the original nine sequences did not fall
      into any of the known phyla of the Archaea suggesting that they may represent a
      novel group within the Kingdom Archaea. Thus, from these two studies, we suggest
      that Archaea in the Cariaco Basin could be unique; however, further studies using
      archaeal-specific primers and the design of new primers as well as the systematic
      use of several different primer combinations may improve the chances of
      understanding the archeal diversity in the Cariaco Basin.

PMID- 18337691
TI  - Arthrobacter soli sp. nov., a novel bacterium isolated from wastewater reservoir
      sediment.
AB  - A novel Gram-positive bacterium, designated SYB2T, was isolated from wastewater
      reservoir sediment, and a polyphasic taxonomic study was conducted based on its
      morphological, physiological, and biochemical features, as well as the analysis
      of its 16S rRNA gene sequence. During the phylogenetic analysis of the strain
      SYB2T, results of a 16S rRNA gene sequence analysis placed this bacterium in the
      genus Arthrobacter within the family Micrococcaceae. SYB2T and Arthrobacter
      protophormiae ATCC 19271T, the most closely related species, both exhibited a 16S
      rRNA gene sequence similarity of 98.99%. The genomic DNA G+C content of the novel
      strain was found to be 62.0 mol%. The predominant fatty acid composition was
      anteiso-C15:0, anteiso-C17:0, iso-C16:0, and iso-C15:0. Analysis of 16S rRNA gene
      sequences and DNA-DNA relatedness, as well as physiological and biochemical
      tests, showed genotypic and phenotypic differences between strain SYB2T and other
      Arthrobacter species. The type strain of the novel species was identified as
      SYB2T (= KCTC 19291T= DSM 19449T).

PMID- 18337692
TI  - Isolation and taxonomic characterization of a novel type I methanotrophic
      bacterium.
AB  - A methane-oxidizing bacterium was isolated from the effluent of manure and its
      molecular and biochemical properties were characterized. The isolate was aerobic,
      Gram-negative, and non-motile. The organism had a type I intracytoplasmic
      membrane structure and granular inclusion bodies. The outer cell wall surface (S
      layers) was tightly packed with cup-shaped structures. Colonies were light yellow
      on nitrate mineral salt agar medium. In addition, the organism was catalase and
      oxidase positive. The isolate used the ribulose monophosphate (RuMP) pathway for
      carbon assimilation, and was able to utilize methane and methanol as a sole
      carbon and energy source, however, it could not utilize any other organic
      compounds that were tested. The cells grew well in a mixture of methane and air
      (methane:air=1:1, v/v) in a compulsory circulation diffusion system, and when
      grown under those conditions, the optimum pH was approximately 7.0 and the
      optimal temperature was 30 degrees. In addition, the specific growth rate and
      generation time were 0.13 per h and 5.43 h, respectively, when grown under the
      optimum conditions. The major ubiquinone was Q-8, and the G+C mol% of the DNA was
      55.3. Phylogenetic analyses based on the 16S rRNA gene sequence comparisons
      showed that this bacterium belongs to a group of type I methanotrophs, and that
      it is most closely related to Methylomicrobium, with a sequence similarity of
      99%. Therefore, the isolate was named Methylomicrobium sp. HG-1.

PMID- 18337693
TI  - Purification and characterization of thermostable beta-glucosidase from the brown
      rot basidiomycete Fomitopsis palustris grown on microcrystalline cellulose.
AB  - An extracellular beta-glucosidase was purified 154-fold to electrophoretic
      homogeneity from the brown-rot basidiomycete Fomitopsis palustris grown on 2.0%
      microcrystalline cellulose. SDS-polyacrylamide gel electrophoresis gel gave a
      single protein band and the molecular mass of purified enzyme was estimated to be
      approximately 138 kDa. The amino acid sequences of the proteolytic fragments
      determined by nano-LC-MS/MS suggested that the protein has high homology with
      fungal beta-glucosidases that belong to glycosyl hydrolase family 3. The Kms for
      p-nitorophenyl-beta-D-glucoside (p-NPG) and cellobiose hydrolyses were 0.117 and
      4.81 mM, and the Kcat values were 721 and 101.8 per sec, respectively. The enzyme
      was competitively inhibited by both glucose (Ki= 0.35 mM) and gluconolactone (Ki=
      0.008 mM), when p-NPG was used as substrate. The optimal activity of the purified
      beta-glucosidase was observed at pH 4.5 and 70 degrees. The F. palustris protein
      exhibited half-lives of 97 h at 55 degrees and 15 h at 65 degrees, indicating
      some degree of thermostability. The enzyme has high activity against p-NPG and
      cellobiose but has very little or no activity against p-nitrophenyl-beta
      lactoside, p-nitrophenyl-beta-xyloside, p-nitrophenyl-alpha-arabinofuranoside,
      xylan, and carboxymethyl cellulose. Thus, our results revealed that the beta
      glucosidase from F. palustris can be classified as an aryl-beta-glucosidase with
      cellobiase activity.

PMID- 18337694
TI  - 5' Untranslated region of the Pseudomonas putida WCS358 stationary phase sigma
      factor rpoS mRNA is involved in RpoS translational regulation.
AB  - The sigmas subunit of RNA polymerase is a central regulator which governs the
      expression of a host of stationary phase-induced and osmotically regulated genes
      in Gram-negative bacteria. The Pseudomonas putida rpoS gene is transcribed as a
      monocistronic rpoS mRNA with a 368 nucleotide-long 5' untranslated region (5'
      UTR). In this study, we investigate the posttranscriptional control of RpoS
      synthesis using rpoS-lacZ transcriptional and translational fusions consisting of
      the native promoter and deletions of 5' UTR or insertion into UTR. The differing
      activity of constructed translational fusions strongly indicated that the 5' UTR
      is involved in the translational regulation of RpoS expression in the stationary
      phase. The results obtained herein demonstrated that the structure of UTR
      performs an important function in the translational regulation of the rpoS gene.

PMID- 18337695
TI  - Molecular characteristics of two laccase from the basidiomycete fungus Polyporus
      brumalis.
AB  - Two laccase cDNAs, pblac1 and pblac2, were cloned from a white-rot fungus strain,
      Polyporus brumalis (KFRI 20912). The cloned cDNAs consisted of 1,829 bp and 1,804
      bp, and their open reading frames encoded proteins of 520 and 524 amino acids,
      with calculated molecular masses of approximately 55.9 kDa and 56 kDa,
      respectively. The deduced amino acid sequences of each protein showed 70%
      similarity. The copper binding regions were conserved in both proteins, as in
      other fungal laccases. RT-PCR analysis revealed that the transcript levels of the
      two laccases increased progressively in shallow stationary culture liquid medium.
      The transcript level of each laccase was induced when the fungus was exposed to
      di-butyl phthalate (DBP), suggesting that the two laccases are involved in DBP
      degradation. The overexpression of the pblac1 gene was derived by the promoter of
      a gene for glyceraldehyde-3-phosphate dehydrogenase, using a homologous system.
      The activity of laccase in the transformants was significantly higher than that
      of the wild type. The identification of these laccase cDNAs was a first step to
      characterize the molecular events related to the lignin degradation ability of
      this basidiomycetous fungus, as well as the degradation of many recalcitrant
      xenobiotics.

PMID- 18337696
TI  - Nitrogen depletion causes up-regulation of glutathione content and gamma
      glutamyltranspeptidase in Schizosaccharomyces pombe.
AB  - This work aims to elucidate the relationship between nitrogen depletion and
      Glutathione (GSH) level in Schizosaccharomyces pombe. The total GSH level was
      much higher in the Pap1-positive KP1 cells than in the Pap1-negative TP108-3C
      cells, suggesting that synthesis of GSH is dependent on Pap1. When the Pap1
      positive KP1 cells were transferred to the nitrogen-depleted medium, total GSH
      level significantly increased up to 6 h and then slightly declined after 9 h.
      Elevation of the total GSH level was observed to be much less with the Pap1
      negative cells. However, glucose deprivation was not able to enhance the GSH
      level in the KP1 cells. Activity of gamma-glutamyltranspeptidase (gamma-GT), an
      enzyme in the first step of GSH catabolism, also increased during nitrogen
      depletion. The total GSH level was more significantly enhanced in the KP1 cells
      overexpressing gamma-GT2 than gamma-GT1 during nitrogen starvation. Reactive
      oxygen species (ROS) levels were not changed during nitrogen starvation in both
      Pap1-positive and Pap1-negative cells. Collectively, nitrogen depletion causes up
      regulation of GSH synthesis and gamma-GT in a Pap1-dependent manner.

PMID- 18337697
TI  - The mutation of a novel Saccharomyces cerevisiae SRL4 gene rescues the lethality
      of rad53 and lcd1 mutations by modulating dNTP levels.
AB  - The SRL4 (YPL033C) gene was initially identified by the screening of
      Saccharomyces cerevisiae genes that play a role in DNA metabolism and/or genome
      stability using the SOS system of Escherichia coli. In this study, we found that
      the srl4Delta mutant cells were resistant to the chemicals that inhibit
      nucleotide metabolism and evidenced higher dNTP levels than were observed in the
      wild-type cells in the presence of hydroxyurea. The mutant cells also showed a
      significantly faster growth rate and higher dNTP levels at low temperature (16
      degrees C) than were observed in the wild-type cells, whereas we detected no
      differences in the growth rate at 30 degrees C. Furthermore, srl4Delta was shown
      to suppress the lethality of mutations of the essential S phase checkpoint genes,
      RAD53 and LCD1. These results indicate that SRL4 may be involved in the
      regulation of dNTP production by its function as a negative regulator of
      ribonucleotide reductase.

PMID- 18337698
TI  - Hepatitis C virus (HCV) genotyping by annealing reverse transcription-PCR
      products with genotype-specific capture probes.
AB  - The genotype of the hepatitis C virus (HCV) strain infecting a given patient is
      an important predictive factor for the clinical outcome of chronic liver disease
      and its response to anti-viral therapeutic agents. We herein sought to develop a
      new easy, sensitive and accurate HCV genotyping method using annealing genotype
      specific capture probes (AGSCP) in an automation-friendly 96-well plate format.
      The validation of our new AGSCP was performed using the Standard HCV Genotype
      Panel. We then used both our AGSCP and the commercially available INNO-LiPA assay
      to analyze the HCV genotypes from 111 Korean patients. Discordant results were
      analyzed by direct sequencing. AGSCP successfully genotyped the standard panel.
      The genotypes of 111 patient samples were also obtained successfully by AGSCP and
      INNO-LiPA. We observed a high concordance rate (93 matched samples, 83.8%)
      between the two assays. Sequencing analysis of the 18 discordant results revealed
      that the AGSCP had correctly identified 12 samples, whereas the INNO-LiPA had
      correctly identified only 6. These results collectively indicate that AGSCP assay
      is a convenient and sensitive method for large-scale genotyping, and it may be a
      promising tool for the determination of HCV and other genotypes in clinical
      settings.

PMID- 18337699
TI  - Characterization and signature pattern analysis of Korean clade HIV-1 using nef
      gene sequences.
AB  - Phylogenetic studies of the HIV-1 gene sequences isolated from Korean patients
      have suggested that most of Korean isolates belong to the subtype B strain. This
      study aims to characterize the Korean clade by molecular phylogenetic analysis
      using all of the Korean nef gene sequences registered in the NCBI GenBank
      (N=422), in addition to 41 reference strains and 94 foreign isolates. Through
      phylogenetic analyses, we verified that most of the Korean isolates belonged to
      the subtype B, where 78.8% are clustered exclusively of foreign isolates. This
      cluster has been named the Korean clade subtype B (KCB) in order to distinguish
      it from other subtype B clusters. Genetic distance analysis suggested that the
      KCB cluster was more homogeneous and clearly distinctive from the non-Korean
      clade subtype B (NKCB). Comparison of consensus amino acid sequences from KCB and
      NKCB revealed that characteristic KCB signature amino acid patterns composed of
      11 amino acid residues, whose frequencies in the KCB were significantly higher
      than in the NKCB. The KCB signature amino acid residues were critical in
      identifying KCB from NKCB, since substitution of the NKCB sequences with KCB
      signature amino acids relocated them to the Koran clade, and vice versa.

PMID- 18337700
TI  - The identification of a novel Pleurotus ostreatus dsRNA virus and determination
      of the distribution of viruses in mushroom spores.
AB  - Double-stranded RNAs and virus particles were identified in Pleurotus ostreatus
      strain Shin-Nong in Korea. Isometric virus particles with a diameter of 33 nm
      were purified, which are similar to other Pleurotus viruses reported previously.
      This strain contains 5 dsRNAs, 8.0, 2.5, 2.4, 2.0, and 1.8 kb in size. The virus
      particles contain 2 dsRNAs, designated RNA-1 (2.5 kb), and RNA-2 (2.4 kb) which
      is a typical pattern of Partitiviridae. A non-encapsidated dsRNA of about 8.0 kb
      also was identified. Partial cDNA from RNA-1 was cloned, and sequence analysis
      revealed that this gene codes for RdRp. The comparison of the sequence from
      partial cDNA clone showed 35% amino acid homology with the C-terminal end of the
      RdRp gene of Helicobasidum mompa virus and Rosalinia necatrix virus. Specific
      primers designed from the partial sequences successfully amplified RT-PCR product
      from the infected mycelium and a single spore culture. We used these primers to
      determine the pattern of distribution of viruses in spores. Of the 96 different
      single spore cultures generated from Shin-Nong strain, a specific RT-PCR product
      was identified in 25 cultures, indicating that about 26% of basidiospores contain
      viruses.

PMID- 18337701
TI  - Cloning and characterization of thermostable esterase from Archaeoglobus
      fulgidus.
AB  - Thermostable esterase gene was cloned (Est-AF) from extremophilic microorganisms,
      Archaeoglobus fulgidus DSM 4304. The protein analysis result showed that Est-AF
      is monomer with total 247 amino acids and molecular weight of estimated 27.5 kDa.
      It also showed repeating units G-X-S-X-G (GHSLG) (residues 86 approximately 90)
      which is reported as active site of known esterases, and the putative catalytic
      triad composed of Ser88, Asp198 and His226. The esterase activity test with
      various acyl chain length of rho-nitrophenol resulted that Est-AF showed highest
      specific activity with rho-nitrophenylbutyrate (pNPC4) and rapidly decrease with
      rho-nitrophenyl ester contain more than 8 carbon chain. These results represent
      that cloned enzyme is verified as a carboxylesterase but not a lipase because
      esterase activity is decreased with rho-nitrophenyl ester contains more than 8
      carbon chains but lipase activity does not affected with carbon chain length.
      Optimum temperature of esterase reaction with rho-nitrophenylbutyrate (pNPC4) was
      80 degrees C. When ketoprofen ethyl ester was used as a substrate, activity of
      Est-AF showed the highest value at 70 degrees C, and 10% of activity still
      remains after 3 h of incubation at 90 degrees C. This result represents Est-AF
      has high thermostability with comparison of other esterases that have been
      reported. However, Est-AF showed low enantioselectivity with ketoprofen ethyl
      ester. Optimum pH of Est-AF is between pH 7.0 and pH 8.0. Km value of ketoprofen
      ethyl ester is 1.6 mM and, Vmax is 1.7 micromole/mg protein/min. Est-AF showed
      similar substrate affinity but slower reaction with ketoprofen ethyl ester
      compare with esterase from mesophilic strain P. fluorescens.

PMID- 18337702
TI  - Isolation of quinupristin/dalfopristin-resistant Streptococcus agalactiae from
      asymptomatic Korean women.
AB  - Seven Streptococcus agalactiae isolates were obtained from the vagina of 80
      asymptomatic women. Three of these isolates showed multi-drug resistant (MDR)
      phenotypes: two isolates were resistant to clarithromycin, clindamycin,
      erythromycin, and tetracycline; and one isolate was resistant to clarithromycin,
      clindamycin, erythromycin, tetracycline, and quinupristin/dalfopristin. There was
      no clonal relationship among the MDR isolates. This is the first report of
      quinupristin/dalfopristin-resistant S. agalactiae.

PMID- 18337706
TI  - Chronic diseases and non-melanoma skin cancer: is there an association?

PMID- 18337708
TI  - T-cell clonality assays: how do they compare?
AB  - The distinction between certain benign cutaneous lymphocytic infiltrates and
      cutaneous T-cell lymphoma (CTCL) can be a challenging problem in clinical
      practice. An imperfect but useful tool in this circumstance is the analysis of T
      cell clonality or monoclonality by assessing T-cell receptor (TCR) gene
      rearrangements. "Monoclonality" describes the origin of a specific human
      malignant tumor from one single cell from which the entire tumor is derived. The
      term is used to describe the early steps in tumorigenesis; in later stages of
      tumor growth and progression, monoclonal tumor cells may acquire a mutator
      phenotype, rendering the genome unstable. The resulting genetic heterogeneity may
      ultimately lead to subclones in the formerly monoclonal population of tumor
      cells.

PMID- 18337709
TI  - Vitamin D regulation of cathelicidin in the skin: toward a renaissance of vitamin
      D in dermatology?
AB  - 1,25-Dihydroxyvitamin D(3), the active form of vitamin D, is a major regulator of
      the expression of the cationic antimicrobial peptide cathelicidin, not only in
      monocytes but also in epidermal keratinocytes. The involvement of cathelicidin in
      wound healing and skin diseases as diverse as psoriasis, rosacea, and atopic
      dermatitis may create new opportunities for the use of vitamin D in dermatology.

PMID- 18337710
TI  - A systems biology approach to anatomic diversity of skin.
AB  - Human skin exhibits exquisite site-specific morphologies and functions. How are
      these site-specific differences specified during development, maintained in adult
      homeostasis, and potentially perturbed by disease processes? Here, we review
      progress in understanding the anatomic patterning of fibroblasts, a major
      constituent cell type of the dermis and key participant in epithelial-mesenchymal
      interactions. The gene expression programs of human fibroblasts largely reflect
      the superimposition of three gene expression profiles that demarcate the
      fibroblast's position relative to three developmental axes. The HOX family of
      homeodomain transcription factors is implicated in specifying site-specific
      transcriptional programs. The use of gene, tiling, and tissue microarrays
      together gives a comprehensive view of the gene regulation involved in patterning
      the skin.

PMID- 18337711
TI  - The role of Smads in skin development.
AB  - Smads are a group of signaling mediators and antagonists of the transforming
      growth factor-beta (TGF-beta) superfamily, responding but not limited to
      signaling from TGF-beta, Activin, and bone morphogenetic proteins (BMPs). As all
      of these three signaling pathways play important roles in skin development, we
      have been actively pursuing studies assessing the role of Smads in skin
      development. Our studies revealed that Smad-4 affects hair follicle
      differentiation primarily by mediating BMP signaling. Smad-7 significantly
      affects hair follicle development and differentiation by blocking the
      TGFbeta/Activin/BMP pathway and by inhibiting WNT/beta-catenin signaling via
      ubiquitin-mediated beta-catenin degradation. In contrast, other Smads may have
      redundant or dispensable functions in skin development. Here, we review the work
      that shows the emergence of Smad functions in skin development via traditional
      and novel signaling pathways.

PMID- 18337712
TI  - Time course of the antiproteinuric and antihypertensive effects of direct renin
      inhibition in type 2 diabetes.
AB  - Inhibition of renin with an active site inhibitor, aliskiren, lowers blood
      pressure (BP) in diabetic patients. Here, we studied the time course of the
      antihypertensive and antiproteinuric effect of renin inhibition in 15 patients
      with type 2 diabetes and elevated urinary albumin/creatinine ratios (UACRs) to
      check whether aliskiren can decrease proteinuria. After a 4-week washout of
      previous medications, patients received aliskiren and furosemide daily for 28
      days followed by a 4-week withdrawal period. Twenty-four-hour BPs were measured
      at baseline throughout treatment and withdrawal periods. The UACR was
      significantly reduced after 2-4 days of treatment with another significant
      reduction after 28 days. Systolic blood pressure (SBP) was significantly lower
      after 7 days with no further reduction after 28 days. The BP returned toward
      baseline 3 days after withdrawal, whereas the UACR was still significantly
      reduced compared with baseline 12 days after withdrawal. Our study shows that
      aliskiren reduced 24 h SBP, and this was associated with a reduction in
      albuminuria in type 2 diabetic patients.

PMID- 18337713
TI  - Long-term outcomes in nondiabetic chronic kidney disease.
AB  - The Modification of Diet in Renal Disease (MDRD) Study examined the effects of
      strict blood pressure control and dietary protein restriction on the progression
      of kidney disease. Here, we retrospectively evaluated outcomes of nondiabetic
      participants with stages 2-4 chronic kidney disease (CKD) from randomized and
      nonrandomized cohorts of the MDRD Study. Kidney failure and survival status
      through December of 2000, were obtained from the US Renal Data System and the
      National Death Index. Event rates were calculated for kidney failure, death, and
      a composite outcome of death and kidney failure. In the 1666 patients, rates for
      kidney failure were four times higher than that for death. Kidney failure was a
      more likely event than death in subgroups based on baseline glomerular filtration
      rate, proteinuria, kidney disease etiology, gender, and race. It was only among
      those older than 65 that the rate for death approximated that for kidney failure.
      In contrast to other populations with CKD, our study of relatively young subjects
      with nondiabetic disease has found that the majority of the participants advanced
      to kidney failure with a low competing risk of death. In such patients, the
      primary emphasis should be on delaying progression of kidney disease.

PMID- 18337714
TI  - Secondary hyperparathyroidism is associated with higher mortality in men with
      moderate to severe chronic kidney disease.
AB  - Secondary hyperparathyroidism is associated with mortality in patients undergoing
      maintenance dialysis treatment. We studied 515 male US veterans with chronic
      kidney disease, who were not yet on dialysis, to see what outcomes were
      associated with secondary hyperparathyroidism in this population. Relationships
      between intact parathyroid hormone levels and all-cause mortality along with the
      composite of mortality or incidence of dialysis were measured in unadjusted and
      adjusted Cox models for case-mix and laboratory variables. Elevated parathyroid
      hormone levels above the upper limit compared to the lower limit of the normal
      range were significantly associated with mortality after adjustments. Higher
      intact parathyroid hormone levels in the upper limit of normal were significantly
      associated with higher mortality overall and showed similar trends in subgroups
      of patients with stage 3 and stage 4-5 chronic kidney disease and with higher and
      lower serum calcium and phosphorus levels. Similar associations were found with
      the composite outcome of mortality or dialysis. Our study shows that secondary
      hyperparathyroidism is independently associated with higher mortality in patients
      with chronic kidney disease but not yet on dialysis.

PMID- 18337715
TI  - [13C2]oxalate absorption in children with idiopathic calcium oxalate urolithiasis
      or primary hyperoxaluria.
AB  - Intestinal oxalate absorption is an important part of oxalate metabolism
      influencing its urinary excretion and its measurement can be a valuable
      diagnostic tool in hyperoxaluric disorders. In this study, we use
      [(13)C(2)]oxalate absorption under standardized dietary conditions to assess
      intestinal oxalate absorption and its impact on urinary oxalate excretion. Tests
      were conducted in age-matched pediatric patients that included 60 with idiopathic
      calcium oxalate urolithiasis, 13 with primary hyperoxaluria, and 35 healthy
      children. In the idiopathic stone formers, median oxalate absorption was
      significantly higher than that in the controls or in patients with primary
      disease. From standardized values obtained in control patients, oxalate
      hyperabsorption was detected in 23 patients with idiopathic disease but not in
      any patients with primary hyperoxaluria; therefore, a significant correlation
      between intestinal absorption and urinary excretion was found only in those with
      the idiopathic disease. We have shown that increased intestinal oxalate
      absorption is an important risk factor of idiopathic calcium oxalate
      urolithiasis. In contrast, low intestinal oxalate absorption in patients with
      primary hyperoxaluria indicates that only foods with excessive oxalate content be
      restricted from their diet.

PMID- 18337716
TI  - Adynamic bone in patients with chronic kidney disease.
AB  - Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern
      because of its potential increased risk for fracture and cardiovascular disease
      (CVD). Prevalence rates for adynamic bone are reportedly increased, although the
      variance for its prevalence and incidence is large. Differences in its prevalence
      are largely attributed to classification and population differences, the latter
      of which constitutes divergent groups of elderly patients having diabetes and
      other comorbidities that are prone to low bone formation. Most patients have
      vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably
      decreases to very low levels during CKD progression. Fortunately, therapy with
      vitamin D receptor activators (VDRAs) appears to be useful in preventing bone
      loss, in part, by its effect to stimulate bone formation and in decreasing CVD
      morbidity, and should be considered as essential therapy regardless of bone
      turnover status. Future studies will depend on assessing cardiovascular outcomes
      to determine whether the risk/reward profile for complications related to VDRA
      and CKD is tolerable.

PMID- 18337717
TI  - Managing anemia in dialysis patients: hemoglobin cycling and overshoot.

PMID- 18337718
TI  - Functional metagenomic profiling of nine biomes.
AB  - Microbial activities shape the biogeochemistry of the planet and macroorganism
      health. Determining the metabolic processes performed by microbes is important
      both for understanding and for manipulating ecosystems (for example, disruption
      of key processes that lead to disease, conservation of environmental services,
      and so on). Describing microbial function is hampered by the inability to culture
      most microbes and by high levels of genomic plasticity. Metagenomic approaches
      analyse microbial communities to determine the metabolic processes that are
      important for growth and survival in any given environment. Here we conduct a
      metagenomic comparison of almost 15 million sequences from 45 distinct
      microbiomes and, for the first time, 42 distinct viromes and show that there are
      strongly discriminatory metabolic profiles across environments. Most of the
      functional diversity was maintained in all of the communities, but the relative
      occurrence of metabolisms varied, and the differences between metagenomes
      predicted the biogeochemical conditions of each environment. The magnitude of the
      microbial metabolic capabilities encoded by the viromes was extensive, suggesting
      that they serve as a repository for storing and sharing genes among their
      microbial hosts and influence global evolutionary and metabolic processes.

PMID- 18337719
TI  - SAR11 marine bacteria require exogenous reduced sulphur for growth.
AB  - Sulphur is a universally required cell nutrient found in two amino acids and
      other small organic molecules. All aerobic marine bacteria are known to use
      assimilatory sulphate reduction to supply sulphur for biosynthesis, although many
      can assimilate sulphur from organic compounds that contain reduced sulphur atoms.
      An analysis of three complete 'Candidatus Pelagibacter ubique' genomes, and
      public ocean metagenomic data sets, suggested that members of the ubiquitous and
      abundant SAR11 alphaproteobacterial clade are deficient in assimilatory sulphate
      reduction genes. Here we show that SAR11 requires exogenous sources of reduced
      sulphur, such as methionine or 3-dimethylsulphoniopropionate (DMSP) for growth.
      Titrations of the algal osmolyte DMSP in seawater medium containing all other
      macronutrients in excess showed that 1.5 x 10(8) SAR11 cells are produced per
      nanomole of DMSP. Although it has been shown that other marine
      alphaproteobacteria use sulphur from DMSP in preference to sulphate, our results
      indicate that 'Cand. P. ubique' relies exclusively on reduced sulphur compounds
      that originate from other plankton.

PMID- 18337720
TI  - Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper
      IgE syndrome.
AB  - The autosomal dominant hyper-IgE syndrome (HIES, 'Job's syndrome') is
      characterized by recurrent and often severe pulmonary infections, pneumatoceles,
      eczema, staphylococcal abscesses, mucocutaneous candidiasis, and abnormalities of
      bone and connective tissue. Mutations presumed to underlie HIES have recently
      been identified in stat3, the gene encoding STAT3 (signal transducer and
      activator of transcription 3) (refs 3, 4). Although impaired production of
      interferon-gamma and tumour-necrosis factor by T cells, diminished memory T-cell
      populations, decreased delayed-type-hypersensitivity responses and decreased in
      vitro lymphoproliferation in response to specific antigens have variably been
      described, specific immunological abnormalities that can explain the unique
      susceptibility to particular infections seen in HIES have not yet been defined.
      Here we show that interleukin (IL)-17 production by T cells is absent in HIES
      individuals. We observed that ex vivo T cells from subjects with HIES failed to
      produce IL-17, but not IL-2, tumour-necrosis factor or interferon-gamma, on
      mitogenic stimulation with staphylococcal enterotoxin B or on antigenic
      stimulation with Candida albicans or streptokinase. Purified naive T cells were
      unable to differentiate into IL-17-producing (T(H)17) T helper cells in vitro and
      had lower expression of retinoid-related orphan receptor (ROR)-gammat, which is
      consistent with a crucial role for STAT3 signalling in the generation of T(H)17
      cells. T(H)17 cells have emerged as an important subset of helper T cells that
      are believed to be critical in the clearance of fungal and extracellular
      bacterial infections. Thus, our data suggest that the inability to produce T(H)17
      cells is a mechanism underlying the susceptibility to the recurrent infections
      commonly seen in HIES.

PMID- 18337721
TI  - SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin.
AB  - The Sir2 deacetylase regulates chromatin silencing and lifespan in Saccharomyces
      cerevisiae. In mice, deficiency for the Sir2 family member SIRT6 leads to a
      shortened lifespan and a premature ageing-like phenotype. However, the molecular
      mechanisms of SIRT6 function are unclear. SIRT6 is a chromatin-associated
      protein, but no enzymatic activity of SIRT6 at chromatin has yet been detected,
      and the identity of physiological SIRT6 substrates is unknown. Here we show that
      the human SIRT6 protein is an NAD+-dependent, histone H3 lysine 9 (H3K9)
      deacetylase that modulates telomeric chromatin. SIRT6 associates specifically
      with telomeres, and SIRT6 depletion leads to telomere dysfunction with end-to-end
      chromosomal fusions and premature cellular senescence. Moreover, SIRT6-depleted
      cells exhibit abnormal telomere structures that resemble defects observed in
      Werner syndrome, a premature ageing disorder. At telomeric chromatin, SIRT6
      deacetylates H3K9 and is required for the stable association of WRN, the factor
      that is mutated in Werner syndrome. We propose that SIRT6 contributes to the
      propagation of a specialized chromatin state at mammalian telomeres, which in
      turn is required for proper telomere metabolism and function. Our findings
      constitute the first identification of a physiological enzymatic activity of
      SIRT6, and link chromatin regulation by SIRT6 to telomere maintenance and a human
      premature ageing syndrome.

PMID- 18337723
TI  - Sophisticated particle-feeding in a large Early Cambrian crustacean.
AB  - Most Cambrian arthropods employed simple feeding mechanisms requiring only low
      degrees of appendage differentiation. In contrast, post-Cambrian crustaceans
      exhibit a wide diversity of feeding specializations and possess a vast ecological
      repertoire. Crustaceans are evident in the Cambrian fossil record, but have
      hitherto been known exclusively from small individuals with limited appendage
      differentiation. Here we describe a sophisticated feeding apparatus from an Early
      Cambrian arthropod that had a body length of several centimetres. Details of the
      mouthparts resolve this taxon as a probable crown-group (pan)crustacean, while
      its feeding style, which allowed it to generate and handle fine food particles,
      significantly expands the known ecological capabilities of Cambrian arthropods.
      This Early Cambrian record predates the major expansions of large-bodied,
      particle-handling crustaceans by at least one hundred million years, emphasizing
      the importance of ecological context in driving adaptive radiations.

PMID- 18337722
TI  - Opposing effects of polyglutamine expansion on native protein complexes
      contribute to SCA1.
AB  - Spinocerebellar ataxia type 1 (SCA1) is a dominantly inherited neurodegenerative
      disease caused by expansion of a glutamine-encoding repeat in ataxin 1 (ATXN1).
      In all known polyglutamine diseases, the glutamine expansion confers toxic
      functions onto the protein; however, the mechanism by which this occurs remains
      enigmatic, in light of the fact that the mutant protein apparently maintains
      interactions with its usual partners. Here we show that the expanded
      polyglutamine tract differentially affects the function of the host protein in
      the context of different endogenous protein complexes. Polyglutamine expansion in
      ATXN1 favours the formation of a particular protein complex containing RBM17,
      contributing to SCA1 neuropathology by means of a gain-of-function mechanism.
      Concomitantly, polyglutamine expansion attenuates the formation and function of
      another protein complex containing ATXN1 and capicua, contributing to SCA1
      through a partial loss-of-function mechanism. This model provides mechanistic
      insight into the molecular pathogenesis of SCA1 as well as other polyglutamine
      diseases.

PMID- 18337724
TI  - The genome: you gain some, you lose some.

PMID- 18337725
TI  - Micro-exons of the cardiac myosin binding protein C gene: flanking introns
      contain a disproportionately large number of hypertrophic cardiomyopathy
      mutations.
AB  - Hypertrophic cardiomyopathy is primarily caused by mutations in genes encoding
      cardiac sarcomere proteins. Large screening studies identify mutations in 35-65%
      of the diagnosed patients and 15-30% of these are discovered within the MYBPC3
      gene encoding the cardiac myosin binding protein C. The aim of this study is to
      determine whether intronic variation flanking the three micro-exons in MYBPC3 is
      disease-causing. Two hundred and fifty unrelated patients with hypertrophic
      cardiomyopathy were genotyped in MYBPC3, using automated single-strand
      conformation polymorphism, and sequenced for confirmation. Mutations located in
      the flanking introns of the MYBPC3 micro-exons were examined using in silico
      methods. Ectopic expression of mRNA in blood leukocytes in the respective
      patients was examined using reverse transcription-PCR. A total of seven mutations
      were discovered in the introns flanking the two micro-exons 10 and 14, but none
      were found in introns flanking exon 11. Functional studies together with co
      segregation analysis indicate that four mutations are associated with HCM, in the
      respective patients. All four mutations result in premature termination codons,
      which suggests that haploinsufficiency is a pathogenic mechanism of this type of
      mutation. It is demonstrated that the use of in silico methods together with RNA
      studies on peripheral blood leukocytes is a useful tool to evaluate the potential
      effects of mutations on pre-mRNA splicing.

PMID- 18337726
TI  - cDNA analyses of CAPN3 enhance mutation detection and reveal a low prevalence of
      LGMD2A patients in Denmark.
AB  - Calpainopathy or limb-girdle muscular dystrophy type 2A (LGMD2A) is generally
      recognized as the most prevalent form of recessive LGMD and is caused by
      mutations in the CAPN3 gene. Out of a cohort of 119 patients fulfilling clinical
      criteria for LGMD2, referred to our neuromuscular clinic, 46 were suspected to
      have LGMD2A, based on western blot results. Four of these patients were shown to
      have LGMD2I upon molecular analysis, whereas 16 of the remaining 42 patients
      harbored mutations in CAPN3 by both direct genomic sequencing and cDNA analyses.
      In 10 patients, we identified both mutant alleles. In three other, only one
      heterozygous mutation could be identified on the genomic level; however, CAPN3
      cDNA analyses demonstrated homozygosity for the mutant allele, indicating the
      presence of an unidentified allele that somehow compromise correct CAPN3 RNA
      processing. In the three remaining patients, only a single heterozygous mutation
      could be identified both at the genomic level and on full-length CAPN3 cDNA. All
      three patients exhibited a highly abnormal western blot for calpain-3 and
      clinical characteristics of LGMD2A. Only three of the genetically confirmed
      LGMD2A patients were of Danish origin, indicating a five- to sixfold lower
      prevalence in Denmark compared to other European countries. A total of 16
      different CAPN3 mutations were identified, of which 5 were novel. The present
      study demonstrates the value of cDNA analysis for CAPN3 in LGMD2A patients and
      indicates that calpainopathy is an uncommon cause of LGMD in the Denmark.

PMID- 18337727
TI  - ARLTS1 germline variants and the risk for breast, prostate, and colorectal
      cancer.
AB  - Recently, a nonsense alteration Trp149Stop in the ARLTS1 gene was found more
      frequently in familial cancer cases versus sporadic cancer patients and healthy
      controls. Here, the role of Trp149Stop or any other ARLTS1 germline variant was
      evaluated on breast, prostate, and colorectal cancer risk. The whole gene was
      screened for germline alterations in 855 familial cancer patients. The five
      observed variants were further screened in 1169 non-familial cancer patients as
      well as in 809 healthy population controls. The Trp149Stop was found at low
      frequencies (0.5-1.2%) in all patient subgroups versus 1.6% in controls, and the
      mutant allele did not co-segregate with disease status in families with multiple
      affected individuals. The CC genotype in the Cys148Arg variant was slightly more
      common among both familial and sporadic breast (odds ratio (OR), 1.48; 95%
      confidence interval (CI), 1.16-1.87; P=0.001) and prostate cancer patients (OR,
      1.50; 95% CI, 1.13-1.99; P=0.005) when compared to controls. A novel ARLTS1
      variant Gly65Val was found at higher frequency among familial prostate cancer
      patients (8 of 164, 4.9%) than in controls (13 of 809, 1.6%; OR, 3.14; 95% CI,
      1.28-7.70, P=0.016). However, after adjusting for multiple testing, none of these
      results were still significant. No association was found with any of the variants
      and colorectal cancer risk. Our results suggest that Trp149Stop is not a
      predisposition allele in breast, prostate, or colorectal cancer in the Finnish
      population, and, while the Gly65Val variant may increase familial prostate cancer
      risk and the Cys148Arg change may affect both breast and prostate cancer risk,
      the evidence is not strong in these data.

PMID- 18337728
TI  - Dysmorphic features, simplified gyral pattern and 7q11.23 duplication reciprocal
      to the Williams-Beuren deletion.
AB  - We report a patient with mild pachygyria, ascertained during a screening of
      subjects with abnormal neuronal migration and/or epilepsy, having a 7q11.23
      duplication reciprocal to the Williams-Beuren critical region (WBCR) deletion. He
      exhibited speech delay and mental retardation together to type II trigonocephaly
      and other abnormalities. The proband's mother carried the same imbalance, though
      her phenotype was milder and no abnormal conformation of the cranium was
      reported. She had suffered a few seizures in infancy, as already described in
      other duplicated subjects. This genomic imbalance, now described in 17 subjects,
      including one parent for each of the four probands, is associated with a variable
      phenotype. Speech impairment is present in most cases; no distinctive facial
      gestalt is recognizable; seizures have been reported in four subjects and brain
      magnetic resonance, performed in eight cases, resulted abnormal in six, while
      detected abnormal neuronal migration in two. Although the clinical description of
      additional cases is needed to delineate a definite phenotypic core for WBCR
      duplications, trigonocephaly, also reported in another dup(7)(q11.23) patient, is
      possibly a trait that, together with speech impairment, may call for clinically
      oriented specific screening. Abnormal development of the cerebral cortex,
      reported also in the Williams-Beuren deletion, suggests that at least one gene is
      present in the critical region whose deletion/duplication impairs neuronal
      migration.

PMID- 18337729
TI  - Unaffected patients with a homozygous absence of the SMN1 gene.
AB  - In this report, we present three families in which we identified asymptomatic
      carriers of a homozygous absence of the SMN1 gene. In the first family, the
      bialleleic deletion was found in three of four siblings: two affected brothers
      (SMA type 3a and 3b) and a 25-years-old asymptomatic sister. All of them have
      four SMN2 copies. In the second family, four of six siblings are affected (three
      suffer from SMA2 and one from SMA3a), each with three SMN2 copies. The clinically
      asymptomatic 47-year-old father has the biallelic deletion and four SMN2 copies.
      In the third family, the biallelic SMN1 absence was found in a girl affected with
      SMA1 and in her healthy 53-years-old father who had five SMN2 copies. Our
      findings as well as those of other authors show that an increased number of SMN2
      copies in healthy carriers of the biallelic SMN1 deletion is an important SMA
      phenotype modifier, but probably not the only one.

PMID- 18337730
TI  - In tandem analysis of CLCN1 and SCN4A greatly enhances mutation detection in
      families with non-dystrophic myotonia.
AB  - Non-dystrophic myotonias (NDMs) are caused by mutations in CLCN1 or SCN4A. The
      purpose of the present study was to optimize the genetic characterization of NDM
      in The Netherlands by analysing CLCN1 and SCN4A in tandem. All Dutch consultant
      neurologists and the Dutch Patient Association for Neuromuscular Diseases
      (Vereniging Spierziekten Nederland) were requested to refer patients with an
      initial diagnosis of NDM for clinical assessment and subsequent genetic analysis
      over a full year. Based on clinical criteria, sequencing of either CLCN1 or SCN4A
      was performed. When previously described mutations or novel mutations were
      identified in the first gene under study, the second gene was not sequenced. If
      no mutations were detected in the first gene, the second gene was subsequently
      also analysed. Underlying NDM mutations were explored in 54 families. In total,
      20% (8 of 40) of our probands with suspected chloride channel myotonia showed no
      CLCN1 mutations but subsequent SCN4A screening revealed mutations in all of them.
      All 14 probands in whom SCN4A was primarily sequenced showed a mutation. In
      total, CLCN1 mutations were identified in 32 families (59%) and SCN4A in 22
      (41%), resulting in a diagnostic yield of 100%. The yield of mutation detection
      was 93% with three recessive and three sporadic cases not yielding a second
      mutation. Among these mutations, 13 in CLCN1 and 3 in SCN4A were novel. In
      conclusion, the current results show that in tandem analysis of CLCN1 and SCN4A
      affords high-level mutation ascertainment in families with NDM.

PMID- 18337731
TI  - Testing informative missingness in genetic studies using case-parent triads.
AB  - In genetic studies, the transmission/disequilibrium test (TDT) using case-parent
      triads has gained popularity attributable to its robustness to population
      admixture. Several extensions have been proposed to accommodate incomplete
      triads. Some strategies assume that parental genotypes are missing completely at
      random (MCAR) to insure an unbiased conclusion and some methods allow parental
      genotypes to be missing informatively, resulting in reduced power when the
      missing data pattern is indeed MCAR. However, these tests assumed that offspring
      genotypes were MCAR. Recently, Guo indicated that when offspring genotypes were
      missing informatively, an occurrence that can be considered as ascertainment
      bias, inflated type-I error and/or reduced power may occur using the TDT when
      incomplete triads are excluded. In an effort to avoid an erroneous conclusion, we
      propose a strategy called testing informative missingness (TIM) that compares
      conditional distributions of parental genotypes among complete triads and
      incomplete data with only one parent to examine the missing data pattern. Through
      computer simulations, TIM has decent power to detect informative missingness and
      is robust to population admixture. In addition, we illustrate TIM with an
      application to the Framingham Heart Study.

PMID- 18337732
TI  - Prostate-specific antigen and prostate cancer: prediction, detection and
      monitoring.
AB  - Testing for prostate-specific antigen (PSA) has profoundly affected the diagnosis
      and treatment of prostate cancer. PSA testing has enabled physicians to detect
      prostate tumours while they are still small, low-grade and localized. This very
      ability has, however, created controversy over whether we are now diagnosing and
      treating insignificant cancers. PSA testing has also transformed the monitoring
      of treatment response and detection of disease recurrence. Much current research
      is directed at establishing the most appropriate uses of PSA testing and at
      developing methods to improve on the conventional PSA test.

PMID- 18337733
TI  - Lessons from multidisciplinary translational trials on anti-angiogenic therapy of
      cancer.
AB  - The importance of multidisciplinary translational clinical trials is obvious;
      however, making them work is complex and challenging. Here I present an argument
      for designing and implementing multidisciplinary mechanistic trials and present
      the lessons our team at the Massachusetts General Hospital Cancer Center has
      learned from two such trials in cancer patients with locally advanced rectal
      carcinomas and recurrent glioblastomas.

PMID- 18337736
TI  - Regarding the paper: hydroview lens implant calcification-186 exchanges at a
      district general hospital, by P Syam et al.

PMID- 18337737
TI  - Low-density lipoprotein profile changes during the neonatal period.
AB  - OBJECTIVE: To investigate natural change of low-density lipoprotein (LDL) profile
      during the neonatal period and the impact of gestational age and birth weight on
      those changes. STUDY DESIGN: We measured lipid composition in LDL fraction, LDL
      particle size and apolipoprotein B (apoB) concentration at birth, 5 days of age
      and 1 month of age in 63 healthy neonates that had 37 to 41-week gestational age.
      RESULT: Low-density lipoprotein cholesterol and apoB concentrations increased
      from birth to 5 days of age, and the concentration persisted at 1 month in breast
      fed and mixed-fed infants. However, in formula-fed infants, the concentration
      decreased at 1 month. At 5 days of age, neonates had larger and more triglyceride
      (TG)-rich LDL particles than at birth. At 1 month of age, LDL particles were
      smaller and more cholesterol rich than at 5 days of age. Single regression
      analyses showed that gestational age had influenced the LDL profile at birth and
      5 days of age, while at 1 month milk determined the profile. CONCLUSION: The
      number of LDL particles increased rapidly during the first 5 days of life, and
      the composition of LDL particles is modulated by TG content throughout the
      neonatal period. Gestational age and milk, rather than birth weight, determine
      postnatal changes in LDL profile.

PMID- 18337738
TI  - Global notes: mysteries of 'the first' and the 'last breath' and the gift of
      Neonatal Resuscitation Program.
AB  - First and last breaths define the life span of a living animal including humans.
      Humans have been fascinated more with the last breath-the death. Neonatologists
      are focused on initiating the first breath. Millions of babies around the world
      do not have a chance of survival beyond a few moments after birth for lack of
      successful initiation of their first breath. Both neonatologists and other health
      care providers work hard to separate the last breath from the first breath using
      resuscitative measures thanks to the NRP developed and propagated two decades
      ago. This paper is dedicated to the initiators of the program, and all those
      dedicated health care teams working around the globe to save newborn lives.

PMID- 18337739
TI  - Adherence to NICU transfusion guidelines: data from a multihospital healthcare
      system.
AB  - OBJECTIVE: We critically reviewed every NICU blood component transfusion (packed
      erythrocytes, platelets, frozen plasma (FP) and cryoprecipitate) administered
      during a one-year period. This was done to determine the proportion of
      transfusions given out of compliance with the Intermountain Healthcare
      transfusion guidelines, and to look for patterns of non-compliance that could be
      addressed by quality improvement measures. STUDY DESIGN: A detailed review was
      made of every transfusion administered to patients with a date of birth of 1
      January 2006 through 31 December 2006, in any of three level III, perinatal
      center-associated NICUs within Intermountain Healthcare. RESULT: During 2006 the
      three NICUs cared for 1759 neonates. Seventeen percent of these received one or
      more (median 3) erythrocyte transfusions, 4% received one or more (median 3)
      platelet transfusions, 6% received one or more (median 1) FP infusions and 2%
      received cryoprecipitate (median 1 dose). Seventy percent of the erythrocyte
      transfusions were given in compliance with the guidelines, as were 69% of the
      platelet transfusions, 65% of the FP transfusions and 94% of the cryoprecipitate
      administrations. Patients who received large numbers of transfusions were more
      likely to receive transfusion that violated the guidelines. Forty-five percent of
      patients who received 1 to 3 transfusions received all transfusions within
      guidelines. However, only 18% of patients who received 4 to 10 transfusions
      received all within guidelines. No patient who received >10 transfusions received
      all within the guidelines. Erythrocyte transfusions given early in the hospital
      course were likely to be within guidelines; 72% (588/818) in the first 29 days
      were compliant with guidelines, but compliance fell to 61% (144/237) for
      transfusions administered after 29 days (P=0.002). About half of the platelet
      transfusions given early in the hospital course were in violation of guidelines,
      but after day 9, 83% of platelet transfusions were compliant with guidelines
      (P=0.000). CONCLUSION: Opportunities exist in our healthcare system to improve
      compliance with our transfusion guidelines. Such opportunities are greatest among
      neonates receiving multiple transfusions, among those receiving erythrocyte
      transfusions late in their NICU course and among those receiving platelet
      transfusions early in their NICU course.

PMID- 18337741
TI  - Maternal-administered physical activity enhances bone mineral acquisition in
      premature very low birth weight infants.
AB  - OBJECTIVE: To determine if physical activity delivered by an infant's mother
      would be as effective in promoting bone mineral acquisition in preterm very low
      birth weight (VLBW) infants as the same intervention administered by a trained
      therapist. PATIENTS AND METHODS: Preterm VLBW infants were randomized to receive
      daily physical activity administered by the infant's mother (MOM, n=11) or a
      trained therapist (OT, n=11), or control (n=11). Physical activity consisted of
      range of motion movements against passive resistance to all extremities for 5 to
      10 min daily. All infants were fed mother's milk with fortification to 24 kcal
      oz(-1). Dual energy x-ray of the forearm bone area (BA, cm(2)), mineral content
      (BMC, g), and density (BMD, g/cm(2)) and measurement of bone formation (bone
      specific alkaline phosphatase, BAP) and resorption (urine pyridinium crosslinks
      of collagen, Pyd) were obtained at study entry and at 2.0 kg of body weight.
      RESULT: Forearm BA and BMC gains were greater in MOM and OT infants compared to
      the control infants despite similar postnatal growth rate and nutrient intake.
      Serum BAP levels decreased in controls but remained unchanged in MOM and OT
      infants. Urine Pyd levels were similar at baseline to 2.0 kg for all groups.
      These findings suggest greater bone growth and mineral acquisition in MOM and OT
      infants than control infants. CONCLUSION: This study demonstrates that a physical
      activity program administered by the infant's own mother is as equally effective
      as therapist-administered physical activity in promoting greater bone growth and
      mineral acquisition in preterm VLBW infants.

PMID- 18337740
TI  - Predictors of death or bronchopulmonary dysplasia in preterm infants with
      respiratory failure.
AB  - OBJECTIVES: To identify the variables that predict death/physiologic
      bronchopulmonary dysplasia (BPD) in preterm infants with severe respiratory
      failure. STUDY DESIGN: The study was a secondary analysis of data from the NICHD
      Neonatal Research Network trial of inhaled nitric oxide (iNO) in preterm infants.
      Stepwise logistic regression models and Classification and Regression Tree (CART)
      models were developed for the outcome of death or physiologic BPD (O(2) at 36
      weeks post-menstrual age). RESULT: Death and/or BPD was associated with lower
      birth weight, higher oxygen requirement, male gender, additional surfactant
      doses, higher oxygenation index and outborn status, but not the magnitude of
      response in PaO(2) to iNO. The positive predictive value of the CART model was
      82% at 95% sensitivity. CONCLUSIONS: The major factors associated with death/BPD
      were an increased severity of respiratory failure, lower birth weight, male
      gender and outborn status, but not the magnitude of initial response to iNO.

PMID- 18337742
TI  - Hydrocortisone administration for the treatment of refractory hypotension in
      critically ill newborns.
AB  - OBJECTIVE: The purpose of this observation was to evaluate the safety and
      efficacy of hydrocortisone (HC) for the treatment of refractory hypotension in
      term and preterm infants. A secondary purpose was to determine the utility of
      serum cortisol concentrations in predicting the response to treatment. STUDY
      DESIGN: This is a retrospective observational study of 117 infants treated with a
      standardized HC protocol for refractory hypotension. Refractory hypotension was
      defined as a mean arterial pressure (MAP) less than the gestational age (GA)
      despite a total inotrope dose of 20 microg per kg per min. Baseline serum
      cortisol concentrations were determined prior to treatment with stress dose HC.
      RESULT: Treatment with HC increased the MAP at 2, 6, 12 and 24 h after
      initiation, decreased the total inotrope dose at 6, 12 and 24 h, and was
      associated with resolution of oliguria. There was no correlation between the
      pretreatment baseline cortisol concentration and GA, birth weight or the response
      to treatment. The incidence of grades III to IV intraventricular hemorrhage,
      periventricular leukomalacia, bacterial or fungal sepsis and spontaneous
      intestinal perforation (SIP) after HC treatment was similar to institutional
      historic controls prior to institution of this standardized HC protocol.
      CONCLUSION: HC treatment was associated with a rapid resolution of cardiovascular
      compromise. The incidence of significant side effects was similar to that in
      previously published reports, including a comparable incidence of SIP. On the
      basis of our results, measuring baseline serum cortisol concentration to guide
      the management of refractory hypotension is unwarranted.

PMID- 18337743
TI  - Improved growth and decreased morbidities in <1000 g neonates after early
      management changes.
AB  - OBJECTIVE: To test the hypothesis that three changes in the early management of
      extremely low birth weight (ELBW) neonates would decrease the incidence of extra
      uterine growth restriction (EUGR) by 25%. The three early management practice
      changes (EMPC) included surfactant at delivery followed by immediate extubation
      to nasal continuous positive airway pressure (CPAP), decreased oxygen exposure
      and early parenteral amino acids. STUDY DESIGN: Historical cohort study of
      preterm infants<or=1000 g birth weight (BW) born at the University of Texas
      Medical Branch between January 2001 and June 2002 (pre-EMPC, before changes,
      n=87) and July 2004 to December 2005 (post-EMPC, after changes, n=76). Outcomes
      measured included feeding and growth parameters, morbidities and interventions.
      Statistical analysis included chi2-analysis, Student's t-test, and analysis of
      variance. RESULT: Infants in the post-EMPC cohort regained BW more quickly,
      maintained appropriate size for weight at 36 weeks and had less morbidity
      associated with poor long-term outcome. Predictors of EUGR included BW<750 g and
      surgical necrotizing enterocolitis. CONCLUSION: The introduction of surfactant at
      delivery followed by immediate extubation to CPAP, decreased oxygen exposure and
      early parenteral amino acids in ELBW infants is possible, safe and associated
      with improvements in growth and morbidity.

PMID- 18337744
TI  - Pregnancy outcome in fetuses with increased nuchal translucency.
AB  - OBJECTIVE: The aim of this study was to examine fetal and neonatal outcomes in
      the setting of nuchal translucency (NT) > or =3 mm at routine first-trimester
      screening. STUDY DESIGN: A nested case-series study within a retrospective cohort
      of women screened for Down syndrome at 11-14 weeks of gestation. Crown-rump
      length, NT values and additional anomalies at first and early second trimesters
      were recorded. Follow-up information was obtained by a review of medical records
      and self-report from patients. Adverse outcomes included fetal death and
      termination of pregnancy due to structural or chromosomal anomalies. RESULT: A
      total of 1930 pregnant women were screened between 11 and 14 weeks of gestation.
      The prevalence of increased fetal NT (> or =3 mm) was 1.4% (n=27). Among these,
      12 showed increased fetal NT as an isolated finding. In this group, 2 women
      experienced fetal demise (16%) and 10 delivered healthy babies. In the group with
      additional abnormalities (n=15), 9 (60%) were found to have chromosomal
      abnormalities, all of which were terminated. For all cases with increased fetal
      NT, total incidence of adverse outcome was 62%. CONCLUSION: At first-trimester
      ultrasonography, a fetal NT > or =3 mm was associated with a high incidence of
      chromosomal abnormalities in the presence of associated abnormalities. For cases
      with the increased fetal NT at first-trimester fetal assessment and follow-up is
      necessary to detect possible adverse outcomes.

PMID- 18337745
TI  - Early discontinuation of intravenous prostaglandin E1 after balloon atrial
      septostomy is associated with an increased risk of rebound hypoxemia.
AB  - OBJECTIVE: A comparison of the effects of early (<2 h) and late (>or=2 h)
      discontinuation of prostaglandin E1 (PGE1), on systemic oxygenation following a
      successful balloon atrial septostomy (BAS), in neonates with confirmed diagnosis
      of d-transposition of the great arteries (d-TGA). STUDY DESIGN: Neonates with a
      postnatal diagnosis of d-TGA who were admitted to a quaternary neonatal intensive
      care unit between January 1999 and December 2004 were identified from the local
      database. The effects of time of discontinuation of PGE1 on oxygen saturations,
      oxygen requirement, need for reinstitution of prostaglandin infusion and
      postoperative stability were analyzed. RESULT: Sixty neonates with a diagnosis of
      d-TGA were identified, 45 of whom had a BAS performed. Of these, 25 cases had
      early (<2 h) discontinuation of PGE1 whereas in the remaining 20 discontinuation
      was late (>or=2 h). PGE1 infusion was recommenced in 20 neonates (20/45 (44%))
      after a successful BAS due to rebound hypoxemia. Of these, there was a threefold
      increase in the need for reinstitution of prostaglandin in the early compared to
      late discontinuation group (16/25 (64%) vs 4/20 (20%), P<0.006). There was no
      difference in postoperative cardiorespiratory stability. CONCLUSION: Early
      discontinuation of intravenous PGE1 following BAS was associated with an
      increased risk of rebound hypoxemia, necessitating the recommencement of PGE1. We
      speculate the rapid improvement in oxygenation on reinstitution of PGE1 is
      secondary to pulmonary vasodilation and improved pulmonary blood flow. We propose
      a more cautious and graded approach to discontinuation of PGE1 based on illness
      severity and the magnitude and duration of hypoxemia at presentation.

PMID- 18337746
TI  - eIF2-dependent and eIF2-independent modes of initiation on the CSFV IRES: a
      common role of domain II.
AB  - Specific interactions of the classical swine fever virus internal ribosomal entry
      site (IRES) with 40S ribosomal subunits and eukaryotic translation initiation
      factor (eIF)3 enable 43S preinitiation complexes containing eIF3 and eIF2-GTP-Met
      tRNA(iMet) to bind directly to the initiation codon, yielding 48S initiation
      complexes. We report that eIF5B or eIF5B/eIF3 also promote Met-tRNA(iMet) binding
      to IRES-40S complexes, forming 48S complexes that can assemble elongation
      competent ribosomes. Although 48S complexes assembled both by eIF2/eIF3- and
      eIF5B/eIF3-mediated Met-tRNA(iMet) recruitment were destabilized by eIF1,
      dissociation of 48S complexes formed with eIF2 could be out-competed by efficient
      subunit joining. Deletion of IRES domain II, which is responsible for
      conformational changes induced in 40S subunits by IRES binding, eliminated the
      sensitivity of 48S complexes assembled by eIF2/eIF3- and eIF5B/eIF3-mediated
      mechanisms to eIF1-induced destabilization. However, 48S complexes formed by the
      eIF5B/eIF3-mediated mechanism on the truncated IRES could not undergo efficient
      subunit joining, as reported previously for analogous complexes assembled with
      eIF2, indicating that domain II is essential for general conformational changes
      in 48S complexes, irrespective of how they were assembled, that are required for
      eIF5-induced hydrolysis of eIF2-bound GTP and/or subunit joining.

PMID- 18337747
TI  - The bacterial flagellar switch complex is getting more complex.
AB  - The mechanism of function of the bacterial flagellar switch, which determines the
      direction of flagellar rotation and is essential for chemotaxis, has remained an
      enigma for many years. Here we show that the switch complex associates with the
      membrane-bound respiratory protein fumarate reductase (FRD). We provide evidence
      that FRD binds to preparations of isolated switch complexes, forms a 1:1 complex
      with the switch protein FliG, and that this interaction is required for both
      flagellar assembly and switching the direction of flagellar rotation. We further
      show that fumarate, known to be a clockwise/switch factor, affects the direction
      of flagellar rotation through FRD. These results not only uncover a new component
      important for switching and flagellar assembly, but they also reveal that FRD, an
      enzyme known to be primarily expressed and functional under anaerobic conditions
      in Escherichia coli, nonetheless, has important, unexpected functions under
      aerobic conditions.

PMID- 18337748
TI  - VE-cadherin is a critical endothelial regulator of TGF-beta signalling.
AB  - VE-cadherin is an endothelial-specific transmembrane protein concentrated at cell
      to-cell adherens junctions. Besides promoting cell adhesion and controlling
      vascular permeability, VE-cadherin transfers intracellular signals that
      contribute to vascular stabilization. However, the molecular mechanism by which
      VE-cadherin regulates vascular homoeostasis is still poorly understood. Here, we
      report that VE-cadherin expression and junctional clustering are required for
      optimal transforming growth factor-beta (TGF-beta) signalling in endothelial
      cells (ECs). TGF-beta antiproliferative and antimigratory responses are increased
      in the presence of VE-cadherin. ECs lacking VE-cadherin are less responsive to
      TGF-beta/ALK1- and TGF-beta/ALK5-induced Smad phosphorylation and target gene
      transcription. VE-cadherin coimmunoprecipitates with all the components of the
      TGF-beta receptor complex, TbetaRII, ALK1, ALK5 and endoglin. Clustered VE
      cadherin recruits TbetaRII and may promote TGF-beta signalling by enhancing
      TbetaRII/TbetaRI assembly into an active receptor complex. Taken together, our
      data indicate that VE-cadherin is a positive and EC-specific regulator of TGF
      beta signalling. This suggests that reduction or inactivation of VE-cadherin may
      contribute to progression of diseases where TGF-beta signalling is impaired.

PMID- 18337749
TI  - Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity
      by HBD.
AB  - Human RNase H1 contains an N-terminal domain known as dsRHbd for binding both
      dsRNA and RNA/DNA hybrid. We find that dsRHbd binds preferentially to RNA/DNA
      hybrids by over 25-fold and rename it as hybrid binding domain (HBD). The crystal
      structure of HBD complexed with a 12 bp RNA/DNA hybrid reveals that the RNA
      strand is recognized by a protein loop, which forms hydrogen bonds with the 2'-OH
      groups. The DNA interface is highly specific and contains polar residues that
      interact with the phosphate groups and an aromatic patch that appears selective
      for binding deoxyriboses. HBD is unique relative to non-sequence-specific dsDNA-
      and dsRNA-binding domains because it does not use positive dipoles of alpha
      helices for nucleic acid binding. Characterization of full-length enzymes with
      defective HBDs indicates that this domain dramatically enhances both the specific
      activity and processivity of RNase H1. Similar activity enhancement by small
      substrate-binding domains linked to the catalytic domain likely occurs in other
      nucleic acid enzymes.

PMID- 18337750
TI  - The BTG2 protein is a general activator of mRNA deadenylation.
AB  - BTG2 is a prototype member of the BTG/Tob family of antiproliferative proteins,
      originally identified as a primary response gene induced by growth factors and
      tumour promoters. Its expression has been linked to diverse cellular processes
      such as cell-cycle progression, differentiation or apoptosis. BTG2 has also been
      shown to interact with the Pop2/Caf1 deadenylase. Here, we demonstrate that BTG2
      is a general activator of mRNA decay, thereby contributing to gene expression
      control. Detailed characterizations of BTG2 show that it enhances deadenylation
      of all transcripts tested. Our results demonstrate that Caf1 nuclease activity is
      required for efficient deadenylation in mammalian cells and that the deadenylase
      activities of both Caf1 and its Ccr4 partner are required for Btg2-induced
      poly(A) degradation. General activation of deadenylation may represent a new mode
      of global regulation of gene expression, which could be important to allow rapid
      resetting of protein production during development or after specific stresses.
      This may constitute a common function for BTG/Tob family members.

PMID- 18337751
TI  - cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid
      dependent manner.
AB  - The calcium/calmodulin-dependent kinase that phosphorylates and inactivates
      eukaryotic elongation factor 2 (eEF2 kinase; eEF2K) is subject to multisite
      phosphorylation, which regulates its activity. Phosphorylation at Ser359 inhibits
      eEF2K activity even at high calcium concentrations. To identify the kinase that
      phosphorylates Ser359 in eEF2K, we developed an extensive purification protocol.
      Tryptic mass fingerprint analysis identified it as cdc2 (cyclin-dependent kinase
      1). cdc2 co-purifies with Ser359 kinase activity and cdc2-cyclin B complexes
      phosphorylate eEF2K at Ser359. We demonstrate that cdc2 contributes to
      controlling eEF2 phosphorylation in cells. cdc2 is activated early in mitosis.
      Kinase activity against Ser359 in eEF2K also peaks at this stage of the cell
      cycle and eEF2 phosphorylation is low in mitotic cells. Inactivation of eEF2K by
      cdc2 may serve to keep eEF2 active during mitosis (where calcium levels rise) and
      thereby permit protein synthesis to proceed in mitotic cells. Amino-acid
      starvation decreases cdc2's activity against eEF2K, whereas loss of TSC2 (a
      negative regulator of mammalian target of rapamycin complex 1(mTORC1)) increases
      it. These data closely match the control of Ser359 phosphorylation and indicate
      that cdc2 may be regulated by mTORC1.

PMID- 18337752
TI  - Munc18a controls SNARE assembly through its interaction with the syntaxin N
      peptide.
AB  - Sec1/Munc18-like (SM) proteins functionally interact with SNARE proteins in
      vesicular fusion. Despite their high sequence conservation, structurally
      disparate binding modes for SM proteins with syntaxins have been observed.
      Several SM proteins appear to bind only to a short peptide present at the N
      terminus of syntaxin, designated the N-peptide, while Munc18a binds to a 'closed'
      conformation formed by the remaining portion of syntaxin 1a. Here, we show that
      the syntaxin 16 N-peptide binds to the SM protein Vps45, but the remainder of
      syntaxin 16 strongly enhances the affinity of the interaction. Likewise, the N
      peptide of syntaxin 1a serves as a second binding site in the Munc18a/syntaxin 1a
      complex. When the syntaxin 1a N-peptide is bound to Munc18a, SNARE complex
      formation is blocked. Removal of the N-peptide enables binding of syntaxin 1a to
      its partner SNARE SNAP-25, while still bound to Munc18a. This suggests that
      Munc18a controls the accessibility of syntaxin 1a to its partners, a role that
      might be common to all SM proteins.

PMID- 18337753
TI  - Toll-like receptors control autophagy.
AB  - Autophagy is a newly recognized innate defense mechanism, acting as a cell
      autonomous system for elimination of intracellular pathogens. The signals and
      signalling pathways inducing autophagy in response to pathogen invasion are
      presently not known. Here we show that autophagy is controlled by recognizing
      conserved pathogen-associated molecular patterns (PAMPs). We screened a PAMP
      library for effects on autophagy in RAW 264.7 macrophages and found that several
      prototype Toll-like receptor (TLR) ligands induced autophagy. Single-stranded RNA
      and TLR7 generated the most potent effects. Induction of autophagy via TLR7
      depended on MyD88 expression. Stimulation of autophagy with TLR7 ligands was
      functional in eliminating intracellular microbes, even when the target pathogen
      was normally not associated with TLR7 signalling. These findings link two innate
      immunity defense systems, TLR signalling and autophagy, provide a potential
      molecular mechanism for induction of autophagy in response to pathogen invasion,
      and show that the newly recognized ability of TLR ligands to stimulate autophagy
      can be used to treat intracellular pathogens.

PMID- 18337754
TI  - Hypertension in the Asia-Pacific region.

PMID- 18337755
TI  - Hypertension, concurrent cardiovascular risk factors and mortality: the Singapore
      Cardiovascular Cohort Study.
AB  - The current hypertension (HTN) guidelines recommend the assessment of other
      cardiovascular disease (CVD) risk factors in individuals with HTN for further
      management. Few studies in Asian populations have been published to identify the
      outcome of individuals with HTN and other CVD risk factors. This study aims to
      assess the effect of HTN alone, and in combination with other CVD risk factors on
      all-cause and CVD mortality. Three cross-sectional studies carried out in
      Singapore (baseline 1982--1995) consisting of 5830 persons were grouped by the
      absence or presence of HTN and CVD risk factors. They were followed-up (mean 14.1
      years) by linkage with the National Death Register. Cox's proportional hazards
      model was used to obtain adjusted hazard ratios (HRs) for risk of mortality. HTN
      individuals with either <2 CVD risk factors (adjusted HR 1.4; 95% confidence
      interval (CI) 1.0-1.8) or > or =2 CVD risk factors (adjusted HR 2.3; 95% CI 1.9
      3.0) were at increased risk of all-cause mortality compared to normotensive
      individuals. The findings were similar for CVD mortality. HTN individuals who
      also smoked or had diabetes were at highest risk of all-cause mortality, whereas
      those with elevated total cholesterol/high-density lipoprotein cholesterol,
      smoked or diabetes had the highest risk for CVD mortality. These findings show
      that in HTN individuals it is important to assess the presence of other CVD risk
      factors and manage accordingly.

PMID- 18337756
TI  - High serum levels of CXC chemokine ligand 10 in untreated essential hypertension.

PMID- 18337757
TI  - Effects of low-intensity resistance training with slow lifting and lowering on
      vascular function.

PMID- 18337758
TI  - Salt-sensitive men show reduced heart rate variability, lower norepinephrine and
      enhanced cortisol during mental stress.
AB  - Salt sensitivity (SS) represents a risk factor for essential hypertension, which
      has been related to enhanced cardiovascular stress reactivity possibly mediated
      by increased noradrenergic susceptibility. We investigated biophysiological
      responses to mental stress in salt-sensitive (ss) and salt-resistant (sr)
      subjects, hypothesizing lower heart rate variability (HRV) and higher cortisol in
      the ss. A total of 48 healthy normotensive Caucasian men (age 25.6+/-2.6, body
      mass index 22.9+/-2.3) were phenotyped for SS (defined as significant drop in
      mean arterial pressure>3 mm Hg under the low-salt diet) by a 2-week high- versus
      low-salt diet. Subjects underwent a standardized mental stress task with
      continuous cardiovascular monitoring before, during and after the test (Finapres;
      Ohmeda, Louisville, CO, USA). Blood samples were drawn to examine cortisol and
      catecholamines before, after and 20 min after stress. The task elicited
      significant increases of systolic blood pressure (SBP), diastolic BP (DBP) and
      heart rate (HR) and a significant decrease of HRV (all time effects P<0.0001).
      The ss subjects showed lower norepinephrine (NE) and higher cortisol, indicated
      by significant group effects (P=0.009 and 0.025, respectively). HR increased and
      HRV decreased more in the ss under the stress, shown by significant time by group
      interactions (P=0.045 and 0.003, respectively). The observation of a more
      pronounced HR rise coupled with a greater decrease of HRV in healthy ss men under
      the influence of brief mental stress confirms their enhanced physiological stress
      reactivity. The lower peripheral NE may represent an effort to compensate for
      increased noradrenergic receptor sensitivity. The enhanced cortisol levels are
      backed by recent genetic findings on HSD11B2 polymorphisms and may promote
      hypertension.

PMID- 18337759
TI  - Hypertension and cardiac arrhythmias: a review of the epidemiology,
      pathophysiology and clinical implications.
AB  - Hypertension is commonly associated with cardiac arrhythmias in patients with and
      without concomitant cardiovascular disease. Experimental and epidemiological
      studies have demonstrated potential links between hypertension and atrial and
      ventricular arrhythmias, although the underlying pathophysiological mechanism
      remains unclear. Nonetheless, the importance of hypertension as a cause of atrial
      and ventricular arrhythmias is not well recognized. In particular, the occurrence
      of left ventricular hypertrophy is a strong predictor for the development of AF,
      ventricular ectopy and sudden cardiac death. Recent prospective clinical trials
      reveal that antihypertensive therapy may delay or prevent the occurrence of
      cardiac arrhythmias and sudden cardiac death in patients with hypertension.
      Although antihypertensive agents that block the renin-angiotensin-aldosterone
      system appear to protect against cardiac arrhythmias, this needs to be confirmed
      by current ongoing clinical trials.

PMID- 18337760
TI  - Sorafenib inhibits activation of human peripheral blood T cells by targeting LCK
      phosphorylation.
AB  - Sorafenib, a novel drug for metastatic renal cancer, has broad-spectrum activity
      against multiple tyrosine kinases, including Raf-1, vascular endothelial growth
      factor receptor and platelet-derived growth factor receptor. However, little is
      known about its effects on the immune system. In this report, we examine the
      effects of sorafenib on the proliferation and activation of human peripheral
      blood T cells, as well as its effects on T-cell-mediated immune response in mice.
      At concentrations similar to those used in patients, sorafenib inhibited the
      proliferation of primary human T cells in vitro. At more than 10 microM,
      sorafenib caused an irrecoverable inhibition of proliferation, even after drug
      withdrawal. In addition, sorafenib induced T-cell apoptosis at concentrations
      higher than 10 muM. sorafenib also caused G(0)/G(1) phase arrest, inhibition of
      CD25 and CD69 expression, interleukin-2 production and LCK phosphorylation in the
      T cells; all of these effects exhibited dose and time dependence. When tested
      against contact dermatitis in mice, sorafenib significantly reduced the ear
      swelling induced by picryl chloride. These findings suggest that sorafenib may
      cause the loss of T-cell immune response by inducing apoptosis and targeting LCK.
      This could potentially lead to immunosuppression in patients with cancer.

PMID- 18337761
TI  - HoxA9 induces insulin-like growth factor-1 receptor expression in B-lineage acute
      lymphoblastic leukemia.
AB  - The homeobox (Hox) gene family encodes a group of transcription factors
      preferentially expressed during embryonic development and hematopoiesis.
      Deregulation of Hox gene expression is frequently associated with acute leukemia.
      HoxA9 is the most commonly overexpressed Hox gene in acute leukemia. However,
      little is known regarding specific pathways regulated by HoxA9 that promote the
      growth and survival of leukemic cells. We have generated a conditional model of
      HoxA9 activity in the stromal cell dependent, HoxA9 negative, pre-B-cell line B
      lineage-2 (BLIN-2). Conditional HoxA9 activation in BLIN-2 resulted in increased
      proliferation in the presence and absence of stromal cell support. Stimulation of
      HoxA9 activity resulted in increased expression of the c-Myb transcription factor
      and induction of insulin-like growth factor-1 receptor (IGF-1R) surface
      expression. HoxA9-mediated proliferative effects in BLIN-2 cells were abrogated
      when the cells were treated with specific IGF-1R tyrosine kinase inhibitors or
      with an IGF-1R mAb (A12). IGF-1R expression correlated with endogenous HoxA9
      expression in a small panel of mixed lineage leukemia (MLL)/AF4 cell lines. siRNA
      knockdown of endogenous HoxA9 expression in the MLL/AF4-positive cell line RS4;11
      resulted in loss of IGF-1R expression. These data indicate that HoxA9
      overexpression induces IGF-1R expression and subsequently promotes leukemic cell
      growth.

PMID- 18337762
TI  - AML1-Evi-1 specifically transforms hematopoietic stem cells through fusion of the
      entire Evi-1 sequence to AML1.
AB  - The t(3;21) chromosomal translocation seen in blastic crisis of chronic myeloid
      leukemia and secondary leukemias results in a formation of a chimeric protein
      AML1-Evi-1, which suppresses wild-type AML1 function. Loss of AML1 function
      causes expansion of hematopoietic progenitor cells, whereas it is not sufficient
      for the development of leukemia. To identify essential mechanisms through which
      AML1-Evi-1 exerts full leukemogenic potential, we introduced AML1-Evi-1 and its
      mutants in murine bone marrow cells, and evaluated their transforming activities
      by colony replating assays. The transforming activity of AML1-Evi-1 was lost when
      any of the known functional domains of Evi-1 was deleted from the chimeric
      protein, and forced expression of Evi-1 did not transform the AML1-deleted bone
      marrow cells. Unlike the MLL-ENL and AML1-ETO leukemia-related chimeric proteins,
      AML1-Evi-1 could transform only the hematopoietic stem cell fraction. Moreover,
      AML1-Evi-1-transformed cells show a cell-marker profile distinct from that of the
      cells transformed by AML1-ETO, which also suppresses AML1 function. Thus,
      leukemogenic activity of AML1-Evi-1 may be due to activation of molecular
      mechanisms distinct from those activated by MLL-ENL or AML1-ETO in the
      hematopoietic stem cell fractions.

PMID- 18337763
TI  - Fludarabine combination therapy for follicular lymphoma followed by acute myeloid
      leukemia: two further case records.

PMID- 18337764
TI  - Inv(11)(q21q23) fuses MLL to the Notch co-activator mastermind-like 2 in
      secondary T-cell acute lymphoblastic leukemia.

PMID- 18337765
TI  - The immunophenotype of different immature, myeloid and B-cell lineage-committed
      CD34+ hematopoietic cells allows discrimination between normal/reactive and
      myelodysplastic syndrome precursors.
AB  - Occurrence of phenotypic abnormalities in CD34(+) hematopoietic progenitor and
      precursor cells (HPC) and their major B-cell and nonlymphoid compartments has
      been frequently reported in myelodysplastic syndromes (MDS). Here, we analyze for
      the first time the numerical and phenotypic abnormalities of different maturation
      associated subsets of bone marrow (BM) CD34(+) HPC from 50 newly diagnosed MDS
      patients in comparison to normal/reactive BM (n=29). Our results confirm the
      existence of heterogeneously altered phenotypes among CD34(+) HPC from MDS and
      indicate that such variability depends both on the relative distribution of the
      different subsets of CD34(+) HPC committed into the different myeloid and B
      lymphoid compartments, and their immunophenotype (for example, higher reactivity
      for CD117 and CD13 and lower expression of CyMPO, CD64 and CD65 on CD34(+)
      immature and neutrophil precursors), a clear association existing between the
      accumulation of CD34(+) HPC and that of immature CD34(+) HPC. Interestingly,
      expansion of erythroid- and neutrophil-lineage CD34(+) cells is detected in low
      grade MDS at the expense of CD34(+) plasmacytoid dendritic cell and B-cell
      precursors, while expansion of immature CD34(+) precursors occurs in high-grade
      MDS. On the basis of the number and severity of the phenotypic abnormalities
      detected, a scoring system is proposed that efficiently discriminates between
      normal/reactive and MDS CD34(+) HPC, the mean score significantly increasing from
      low- to high-grade MDS.

PMID- 18337766
TI  - Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK,
      PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy.
AB  - The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are frequently
      activated in leukemia and other hematopoietic disorders by upstream mutations in
      cytokine receptors, aberrant chromosomal translocations as well as other genetic
      mechanisms. The Jak2 kinase is frequently mutated in many myeloproliferative
      disorders. Effective targeting of these pathways may result in suppression of
      cell growth and death of leukemic cells. Furthermore it may be possible to
      combine various chemotherapeutic and antibody-based therapies with low molecular
      weight, cell membrane-permeable inhibitors which target the Raf/MEK/ERK,
      PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to ultimately suppress the survival
      pathways, induce apoptosis and inhibit leukemic growth. In this review, we
      summarize how suppression of these pathways may inhibit key survival networks
      important in leukemogenesis and leukemia therapy as well as the treatment of
      other hematopoietic disorders. Targeting of these and additional cascades may
      also improve the therapy of chronic myelogenous leukemia, which are resistant to
      BCR-ABL inhibitors. Furthermore, we discuss how targeting of the leukemia
      microenvironment and the leukemia stem cell are emerging fields and challenges in
      targeted therapies.

PMID- 18337767
TI  - Contributions of the Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways to
      leukemia.
AB  - Mutations and chromosomal translocations occur in leukemic cells that result in
      elevated expression or constitutive activation of various growth factor receptors
      and downstream kinases. The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways
      are often activated by mutations in upstream genes. The Raf/MEK/ERK and
      PI3K/PTEN/Akt/mTOR pathways are regulated by upstream Ras that is frequently
      mutated in human cancer. Recently, it has been observed that the FLT-3 and Jak
      kinases and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN)
      phosphatase are also frequently mutated or their expression is altered in certain
      hematopoietic neoplasms. Many of the events elicited by the Raf/MEK/ERK,
      PI3K/PTEN/Akt/mTOR and Jak/STAT pathways have direct effects on survival
      pathways. Aberrant regulation of the survival pathways can contribute to
      uncontrolled cell growth and lead to leukemia. In this review, we describe the
      Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT signaling cascades and summarize
      recent data regarding the regulation and mutation status of these pathways and
      their involvement in leukemia.

PMID- 18337768
TI  - Complex speciation of humans and chimpanzees.
AB  - Genetic data from two or more species provide information about the process of
      speciation. In their analysis of DNA from humans, chimpanzees, gorillas,
      orangutans and macaques (HCGOM), Patterson et al. suggest that the apparently
      short divergence time between humans and chimpanzees on the X chromosome is
      explained by a massive interspecific hybridization event in the ancestry of these
      two species. However, Patterson et al. do not statistically test their own null
      model of simple speciation before concluding that speciation was complex, and-
      even if the null model could be rejected--they do not consider other explanations
      of a short divergence time on the X chromosome. These include natural selection
      on the X chromosome in the common ancestor of humans and chimpanzees, changes in
      the ratio of male-to-female mutation rates over time, and less extreme versions
      of divergence with gene flow (see ref. 2, for example). I therefore believe that
      their claim of hybridization is unwarranted.

PMID- 18337773
TI  - Markets can save forests.

PMID- 18337774
TI  - Growing pains.

PMID- 18337775
TI  - On message, off target.

PMID- 18337778
TI  - Stem-cell claim gets cold reception.

PMID- 18337779
TI  - Pacific "dwarf" bones cause controversy.

PMID- 18337780
TI  - Brazil goes to war against logging.

PMID- 18337781
TI  - All eyes on the Amazon. Carlos Nobre interviewed by Jeff Tollefson.

PMID- 18337782
TI  - Libya progresses on HIV.

PMID- 18337785
TI  - Probe readies for dip into geyser on Enceladus.

PMID- 18337793
TI  - Astronomy: eyes as big as the sky.

PMID- 18337794
TI  - Business: stepping out.

PMID- 18337795
TI  - Bioterror: the green menace.

PMID- 18337796
TI  - Results of rush to sequence genomes may be nonsense.

PMID- 18337799
TI  - Poor countries left behind in rush to claim sea floor.

PMID- 18337798
TI  - Directive will unleash new generation of coal polluters.

PMID- 18337806
TI  - Drug discovery: fresh hope to can the worms.

PMID- 18337807
TI  - Cosmology: patchy solutions.

PMID- 18337809
TI  - Physical chemistry: did life grind to a start?

PMID- 18337810
TI  - Nitrogen cycle: out of reach.

PMID- 18337812
TI  - Earth science: geomagnetic reversals.

PMID- 18337811
TI  - Biochemistry: radicals by reduction.

PMID- 18337813
TI  - Genetic basis of fitness differences in natural populations.
AB  - Genomics profoundly influences current biology. One of many exciting consequences
      of this revolution is the potential for identifying and studying the genetic
      basis of those traits affecting fitness that are key to natural selection. Recent
      studies using a multitude of genomic approaches have established such genotype
      phenotype relationships in natural populations, giving new insight into the
      genetic architecture of quantitative variation. In parallel, an emerging
      understanding of the quantitative genetics of fitness variation in the wild means
      that we are poised to see a synthesis of ecological and molecular approaches in
      evolutionary biology.

PMID- 18337814
TI  - A new class of anthelmintics effective against drug-resistant nematodes.
AB  - Anthelmintic resistance in human and animal pathogenic helminths has been
      spreading in prevalence and severity to a point where multidrug resistance
      against the three major classes of anthelmintics--the benzimidazoles,
      imidazothiazoles and macrocyclic lactones--has become a global phenomenon in
      gastrointestinal nematodes of farm animals. Hence, there is an urgent need for an
      anthelmintic with a new mode of action. Here we report the discovery of the amino
      acetonitrile derivatives (AADs) as a new chemical class of synthetic
      anthelmintics and describe the development of drug candidates that are
      efficacious against various species of livestock-pathogenic nematodes. These drug
      candidates seem to have a novel mode of action involving a unique, nematode
      specific clade of acetylcholine receptor subunits. The AADs are well tolerated
      and of low toxicity to mammals, and overcome existing resistances to the
      currently available anthelmintics.

PMID- 18337815
TI  - Pyruvate kinase M2 is a phosphotyrosine-binding protein.
AB  - Growth factors stimulate cells to take up excess nutrients and to use them for
      anabolic processes. The biochemical mechanism by which this is accomplished is
      not fully understood but it is initiated by phosphorylation of signalling
      proteins on tyrosine residues. Using a novel proteomic screen for phosphotyrosine
      binding proteins, we have made the observation that an enzyme involved in
      glycolysis, the human M2 (fetal) isoform of pyruvate kinase (PKM2), binds
      directly and selectively to tyrosine-phosphorylated peptides. We show that
      binding of phosphotyrosine peptides to PKM2 results in release of the allosteric
      activator fructose-1,6-bisphosphate, leading to inhibition of PKM2 enzymatic
      activity. We also provide evidence that this regulation of PKM2 by
      phosphotyrosine signalling diverts glucose metabolites from energy production to
      anabolic processes when cells are stimulated by certain growth factors.
      Collectively, our results indicate that expression of this phosphotyrosine
      binding form of pyruvate kinase is critical for rapid growth in cancer cells.

PMID- 18337816
TI  - SATB1 reprogrammes gene expression to promote breast tumour growth and
      metastasis.
AB  - Mechanisms underlying global changes in gene expression during tumour progression
      are poorly understood. SATB1 is a genome organizer that tethers multiple genomic
      loci and recruits chromatin-remodelling enzymes to regulate chromatin structure
      and gene expression. Here we show that SATB1 is expressed by aggressive breast
      cancer cells and its expression level has high prognostic significance (P <
      0.0001), independent of lymph-node status. RNA-interference-mediated knockdown of
      SATB1 in highly aggressive (MDA-MB-231) cancer cells altered the expression of
      >1,000 genes, reversing tumorigenesis by restoring breast-like acinar polarity
      and inhibiting tumour growth and metastasis in vivo. Conversely, ectopic SATB1
      expression in non-aggressive (SKBR3) cells led to gene expression patterns
      consistent with aggressive-tumour phenotypes, acquiring metastatic activity in
      vivo. SATB1 delineates specific epigenetic modifications at target gene loci,
      directly upregulating metastasis-associated genes while downregulating tumour
      suppressor genes. SATB1 reprogrammes chromatin organization and the transcription
      profiles of breast tumours to promote growth and metastasis; this is a new
      mechanism of tumour progression.

PMID- 18337817
TI  - Reflected light from sand grains in the terrestrial zone of a protoplanetary
      disk.
AB  - In the standard model of terrestrial planet formation, the first step in the
      process is for interstellar dust to coagulate within a protoplanetary disk
      surrounding a young star, forming large grains that settle towards the disk
      plane. Interstellar grains of typical size approximately 0.1 microm are expected
      to grow to millimetre- (sand), centimetre- (pebble) or even metre-sized (boulder)
      objects rather quickly. Unfortunately, such evolved disks are hard to observe
      because the ratio of surface area to volume of their constituents is small. We
      readily detect dust around young objects known as 'classical' T Tauri stars, but
      there is little or no evidence of it in the slightly more evolved 'weak-line'
      systems. Here we report observations of a 3-Myr-old star, which show that grains
      have grown to about millimetre size or larger in the terrestrial zone (within
      approximately 3 au) of this star. The fortuitous geometry of the KH 15D binary
      star system allows us to infer that, when both stars are occulted by the
      surrounding disk, it appears as a nearly edge-on ring illuminated by one of the
      central binary components. This work complements the study of terrestrial zones
      of younger disks that have been recently resolved by interferometry.

PMID- 18337818
TI  - Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra.
AB  - DNA is renowned for its double helix structure and the base pairing that enables
      the recognition and highly selective binding of complementary DNA strands. These
      features, and the ability to create DNA strands with any desired sequence of
      bases, have led to the use of DNA rationally to design various nanostructures and
      even execute molecular computations. Of the wide range of self-assembled DNA
      nanostructures reported, most are one- or two-dimensional. Examples of three
      dimensional DNA structures include cubes, truncated octahedra, octohedra and
      tetrahedra, which are all comprised of many different DNA strands with unique
      sequences. When aiming for large structures, the need to synthesize large numbers
      (hundreds) of unique DNA strands poses a challenging design problem. Here, we
      demonstrate a simple solution to this problem: the design of basic DNA building
      units in such a way that many copies of identical units assemble into larger
      three-dimensional structures. We test this hierarchical self-assembly concept
      with DNA molecules that form three-point-star motifs, or tiles. By controlling
      the flexibility and concentration of the tiles, the one-pot assembly yields
      tetrahedra, dodecahedra or buckyballs that are tens of nanometres in size and
      comprised of four, twenty or sixty individual tiles, respectively. We expect that
      our assembly strategy can be adapted to allow the fabrication of a range of
      relatively complex three-dimensional structures.

PMID- 18337819
TI  - Stream denitrification across biomes and its response to anthropogenic nitrate
      loading.
AB  - Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing
      and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing
      more bioavailable nitrogen to enter groundwater and surface waters. Large-scale
      nitrogen budgets show that an average of about 20-25 per cent of the nitrogen
      added to the biosphere is exported from rivers to the ocean or inland basins,
      indicating that substantial sinks for nitrogen must exist in the landscape.
      Streams and rivers may themselves be important sinks for bioavailable nitrogen
      owing to their hydrological connections with terrestrial systems, high rates of
      biological activity, and streambed sediment environments that favour microbial
      denitrification. Here we present data from nitrogen stable isotope tracer
      experiments across 72 streams and 8 regions representing several biomes. We show
      that total biotic uptake and denitrification of nitrate increase with stream
      nitrate concentration, but that the efficiency of biotic uptake and
      denitrification declines as concentration increases, reducing the proportion of
      in-stream nitrate that is removed from transport. Our data suggest that the total
      uptake of nitrate is related to ecosystem photosynthesis and that denitrification
      is related to ecosystem respiration. In addition, we use a stream network model
      to demonstrate that excess nitrate in streams elicits a disproportionate increase
      in the fraction of nitrate that is exported to receiving waters and reduces the
      relative role of small versus large streams as nitrate sinks.

PMID- 18337820
TI  - Influence of the Gulf Stream on the troposphere.
AB  - The Gulf Stream transports large amounts of heat from the tropics to middle and
      high latitudes, and thereby affects weather phenomena such as cyclogenesis and
      low cloud formation. But its climatic influence, on monthly and longer
      timescales, remains poorly understood. In particular, it is unclear how the warm
      current affects the free atmosphere above the marine atmospheric boundary layer.
      Here we consider the Gulf Stream's influence on the troposphere, using a
      combination of operational weather analyses, satellite observations and an
      atmospheric general circulation model. Our results reveal that the Gulf Stream
      affects the entire troposphere. In the marine boundary layer, atmospheric
      pressure adjustments to sharp sea surface temperature gradients lead to surface
      wind convergence, which anchors a narrow band of precipitation along the Gulf
      Stream. In this rain band, upward motion and cloud formation extend into the
      upper troposphere, as corroborated by the frequent occurrence of very low cloud
      top temperatures. These mechanisms provide a pathway by which the Gulf Stream can
      affect the atmosphere locally, and possibly also in remote regions by forcing
      planetary waves. The identification of this pathway may have implications for our
      understanding of the processes involved in climate change, because the Gulf
      Stream is the upper limb of the Atlantic meridional overturning circulation,
      which has varied in strength in the past and is predicted to weaken in response
      to human-induced global warming in the future.

PMID- 18337821
TI  - Diversity and productivity peak at intermediate dispersal rate in evolving
      metacommunities.
AB  - Positive relationships between species diversity and productivity have been
      reported for a number of ecosystems. Theoretical and experimental studies have
      attempted to determine the mechanisms that generate this pattern over short
      timescales, but little attention has been given to the problem of understanding
      how diversity and productivity are linked over evolutionary timescales. Here, we
      investigate the role of dispersal in determining both diversity and productivity
      over evolutionary timescales, using experimental metacommunities of the bacterium
      Pseudomonas fluorescens assembled by divergent natural selection. We show that
      both regional diversity and productivity peak at an intermediate dispersal rate.
      Moreover, we demonstrate that these two patterns are linked: selection at
      intermediate rates of dispersal leads to high niche differentiation between
      genotypes, allowing greater coverage of the heterogeneous environment and a
      higher regional productivity. We argue that processes that operate over both
      ecological and evolutionary timescales should be jointly considered when
      attempting to understand the emergence of ecosystem-level properties such as
      diversity-function relationships.

PMID- 18337822
TI  - Adaptive coding of visual information in neural populations.
AB  - Our perception of the environment relies on the capacity of neural networks to
      adapt rapidly to changes in incoming stimuli. It is increasingly being realized
      that the neural code is adaptive, that is, sensory neurons change their responses
      and selectivity in a dynamic manner to match the changes in input stimuli.
      Understanding how rapid exposure, or adaptation, to a stimulus of fixed structure
      changes information processing by cortical networks is essential for
      understanding the relationship between sensory coding and behaviour.
      Physiological investigations of adaptation have contributed greatly to our
      understanding of how individual sensory neurons change their responses to
      influence stimulus coding, yet whether and how adaptation affects information
      coding in neural populations is unknown. Here we examine how brief adaptation (on
      the timescale of visual fixation) influences the structure of interneuronal
      correlations and the accuracy of population coding in the macaque (Macaca
      mulatta) primary visual cortex (V1). We find that brief adaptation to a stimulus
      of fixed structure reorganizes the distribution of correlations across the entire
      network by selectively reducing their mean and variability. The post-adaptation
      changes in neuronal correlations are associated with specific, stimulus-dependent
      changes in the efficiency of the population code, and are consistent with changes
      in perceptual performance after adaptation. Our results have implications beyond
      the predictions of current theories of sensory coding, suggesting that brief
      adaptation improves the accuracy of population coding to optimize neuronal
      performance during natural viewing.

PMID- 18337823
TI  - The M2 splice isoform of pyruvate kinase is important for cancer metabolism and
      tumour growth.
AB  - Many tumour cells have elevated rates of glucose uptake but reduced rates of
      oxidative phosphorylation. This persistence of high lactate production by tumours
      in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto
      Warburg more than 75 yr ago. How tumour cells establish this altered metabolic
      phenotype and whether it is essential for tumorigenesis is as yet unknown. Here
      we show that a single switch in a splice isoform of the glycolytic enzyme
      pyruvate kinase is necessary for the shift in cellular metabolism to aerobic
      glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to
      express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use
      short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell
      lines and replace it with pyruvate kinase M1. Switching pyruvate kinase
      expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as
      judged by reduced lactate production and increased oxygen consumption, and this
      correlates with a reduced ability to form tumours in nude mouse xenografts. These
      results demonstrate that M2 expression is necessary for aerobic glycolysis and
      that this metabolic phenotype provides a selective growth advantage for tumour
      cells in vivo.

PMID- 18337824
TI  - An allylic ketyl radical intermediate in clostridial amino-acid fermentation.
AB  - The human pathogenic bacterium Clostridium difficile thrives by the fermentation
      of l-leucine to ammonia, CO(2), 3-methylbutanoate and 4-methylpentanoate under
      anaerobic conditions. The reductive branch to 4-methylpentanoate proceeds by
      means of the dehydration of (R)-2-hydroxy-4-methylpentanoyl-CoA to 4-methylpent-2
      enoyl-CoA, which is chemically the most demanding step. Ketyl radicals have been
      proposed to mediate this reaction catalysed by an iron-sulphur-cluster-containing
      dehydratase, which requires activation by ATP-dependent electron transfer from a
      second iron-sulphur protein functionally similar to the iron protein of
      nitrogenase. Here we identify a kinetically competent product-related allylic
      ketyl radical bound to the enzyme by electron paramagnetic resonance spectroscopy
      employing isotope-labelled (R)-2-hydroxy-4-methylpentanoyl-CoA species. We also
      found that the enzyme generated the stabilized pentadienoyl ketyl radical from
      the substrate analogue 2-hydroxypent-4-enoyl-CoA, supporting the proposed
      mechanism. Our results imply that also other 2-hydroxyacyl-CoA dehydratases and
      the related benzoyl-CoA reductases-present in anaerobically living bacteria
      employ ketyl radical intermediates. The absence of radical generators such as
      coenzyme B12, S-adenosylmethionine or oxygen makes these enzymes unprecedented in
      biochemistry.

PMID- 18337827
TI  - Clinicopathological characterization and genomic aberrations in subcutaneous
      panniculitis-like T-cell lymphoma.
AB  - Subcutaneous panniculitis-like T-cell lymphomas (SPTLs) represent a rare,
      difficult-to-diagnose, and poorly characterized subtype of cutaneous T-cell
      lymphomas (CTCLs) affecting younger people more than the other CTCL forms. We
      performed a thorough clinical, immunohistological, and molecular analysis of nine
      Finnish SPTL patients. Specifically, we performed single-cell comparative genomic
      hybridization (CGH) from laser microdissected, morphologically malignant SPTL
      cells, as well as loss of heterozygosity (LOH) and fluorescence in situ
      hybridization (FISH) analysis for the NAV3 (neuron navigator 3) gene. CGH
      revealed large numbers of DNA copy number changes, the most common of which were
      losses of chromosomes 1pter, 2pter, 10qter, 11qter, 12qter, 16, 19, 20, and 22
      and gains of chromosomes 2q and 4q. Some of the DNA copy number aberrations in
      SPTL, such as loss of 10q, 17p, and chromosome 19, overlap with those
      characteristic of common forms of CTCL (mycosis fungoides (MF) and Sezary
      syndrome (SS)), whereas 5q and 13q gains characterize SPTL. Allelic NAV3
      aberrations (LOH or deletion by FISH), previously found in MF and SS, were
      identified in 44% of the SPTL samples. This study demonstrates that SPTL is also
      moleculocytogenetically a uniform entity of CTCL and supports the current World
      Health Organization-European Organization for Research and Treatment of Cancer
      (WHO-EORTC) classification defining SPTL as a subgroup of its own.

PMID- 18337828
TI  - Partial depletion of mitochondrial DNA from human skin fibroblasts induces a gene
      expression profile reminiscent of photoaged skin.
AB  - In photoaged skin, wrinkles result from an increased degradation and a decreased
      de novo synthesis of collagen fibers. At the molecular level, photoaged skin is
      characterized by increased amounts of large-scale deletions of the mitochondrial
      (mt) genome such as the 4,977 bp common deletion. The common deletion can be
      generated in dermal fibroblasts through repetitive ultraviolet (UV) A
      irradiation, and this was found to be associated with an increased expression of
      the collagen-degrading enzyme matrix metalloproteinase-1 (MMP-1). These studies
      did not clarify whether increased MMP-1 expression was caused by a disturbance of
      mtDNA integrity or whether it occurred independently. We have therefore generated
      a phenocopy of cells bearing large-scale deletions of mtDNA by gradually
      depleting the mtDNA from unirradiated human skin fibroblasts. Gradual depletion
      of mtDNA caused a gene expression profile, which was reminiscent of that observed
      in photoaged skin. Accordingly, in these cells an increased expression of MMP-1
      without a concomitant change in tissue inhibitor metalloproteinase-1 as well as a
      decreased expression of collagen type 1 alpha-1, that is, a gene involved in
      collagen de novo synthesis, was observed. This altered gene expression resulted
      from intracellular, mitochondria-derived oxidative stress. Our results support
      the concept that disruption of mt integrity, for example, by UV-induced mtDNA
      mutagenesis, is of pathogenetic relevance for photoaging of human skin.

PMID- 18337829
TI  - "Dermal dendritic cells" comprise two distinct populations: CD1+ dendritic cells
      and CD209+ macrophages.
AB  - A key cell type of the resident skin immune system is the dendritic cell (DC),
      which in normal skin is located in two distinct microanatomical compartments:
      Langerhans cells (LCs), mainly in the epidermis, and dermal DCs (DDCs), in the
      dermis. Here, the lineage of DDCs was investigated using monoclonal antibodies
      and immunohistology. We provide evidence that "DDC" comprise at least two major
      phenotypic populations of dendritic-appearing cells, immature DC expressing CD1,
      CD11c and CD208; and macrophages expressing CD209, CD206, CD163, and CD68. These
      data suggest that dermal dendritic-appearing macrophages comprise a novel part of
      the innate immune response in the resident skin immune system.

PMID- 18337830
TI  - Profibrinolytic effects of metalloproteinases during skin wound healing in the
      absence of plasminogen.
AB  - Genetic ablation of plasminogen (Plg) and pharmacological inhibition of
      metalloproteinase activity by galardin delay skin wound healing in mice, whereas
      the combined inhibition of these two enzyme systems completely prevents healing.
      In this study, the impact of plasmin and metalloproteinases as profibrinolytic
      enzymes has been investigated by comparing skin wound healing in the absence and
      presence of fibrin. Plg deficiency impairs skin wound healing kinetics, but this
      delay is only partially restored in the absence of fibrin. This suggests that
      plasmin-mediated fibrinolysis is the primary, but not the exclusive, requirement
      for healing of wounds in these mice. In addition, we observe that lack of fibrin
      reduces Plg activation significantly during wound healing. The profibrinolytic
      role of metalloproteinases is revealed by the finding that lack of fibrin
      partially restores the otherwise arrested healing of Plg-deficient wounds after
      metalloproteinase inhibition. In conclusion, the residual impairment of skin
      wound healing in the absence of fibrin suggests the existence of a fibrin
      independent substrate(s) for plasmin and metalloproteinases. Furthermore, these
      in vivo data reveal that galardin-sensitive metalloproteinases mediate
      compensatory fibrinolysis to facilitate wound healing in the absence of plasmin.

PMID- 18337831
TI  - Hyperbaric oxygen attenuates apoptosis and decreases inflammation in an ischemic
      wound model.
AB  - The molecular mechanisms whereby hyperbaric oxygen (HBO) improves ischemic wound
      healing remain elusive. In this study, a rat model of wound ischemia was used to
      test the hypothesis that HBO enhances wound healing by modulating hypoxia
      inducible factor-1alpha (HIF-1alpha) signaling. Male Sprague-Dawley rats
      underwent creation of a previously validated ischemic flap. Three groups
      underwent daily treatment: HBO (90 minutes, 2.4 atm); systemic administration of
      the free radical scavenger, N-acetylcysteine (NAC 150 mg kg(-1) intraperitoneal);
      control (neither HBO nor NAC). HBO treatment improved healing of the ischemic
      wounds. Analysis of ischemic wound tissue extracts demonstrated significantly
      reduced expression of HIF-1alpha, p53, and BNip3. Additionally, HBO increased
      expression of Bcl-2 while decreasing cleaved caspase-3. DNA fragmentation was
      abolished and the number of TUNEL-positive cells was reduced compared to the
      other groups. Vascular endothelial growth factor, cyclooxygenase-2, and
      neutrophil infiltration were reduced in ischemic wounds treated with HBO. These
      results indicate that HBO improves ischemic wound healing by downregulation of
      HIF-1alpha and subsequent target gene expression with attenuation of cell
      apoptosis and reduction of inflammation.

PMID- 18337832
TI  - Langerhans cells are not required for efficient skin graft rejection.
AB  - The mechanism of skin allograft rejection has been thought to require
      presentation of graft antigen by resident epidermal Langerhans cells (LCs). We
      have previously engineered mice that have a selective and constitutive absence of
      epidermal LCs. By using donor skin from these LC-deficient mice, we show that LCs
      are not required for rejection of major (FVB --> B6) or minor (H-Y, male -->
      female on B6 background) antigen-mismatched skin grafts. On the FVB background,
      where H-Y mismatched grafts are normally maintained indefinitely, grafts lacking
      LCs are efficiently rejected. Thus, LCs in the donor graft are required for long
      term skin engraftment, which supports a regulatory role for LCs in skin graft
      acceptance.

PMID- 18337833
TI  - Increased melanocytic nevi and nevus density in a G-34T CDKN2A/p16 melanoma-prone
      pedigree.

PMID- 18337835
TI  - The vitamin D receptor is required for mouse hair cycle progression but not for
      maintenance of the epidermal stem cell compartment.

PMID- 18337834
TI  - HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo.
AB  - Vitiligo is a T-cell-mediated autoimmune disease of the skin. Progressive
      depigmentation accelerates in response to stress. Personal trauma, contact with
      bleaching phenols, overexposure to UV, and mechanical injury can lead to
      progressive loss of melanocytes. This study was focused on the role of stress
      protein heat shock protein (HSP)70 for translating stress into an autoimmune
      disease to melanocytes. Intracellular HSP70 can act as a cytoprotectant,
      preventing apoptosis in cells under stress. Isoform HSP70i can be secreted by
      live cells, and in prior in vitro studies, HSP70 has been shown to activate
      dendritic cells and elicit an immune response to chaperoned proteins and
      peptides. Here, the role of HSP70 in precipitating and perpetuating vitiligo was
      assessed in vivo in a mouse model of autoimmune vitiligo. In this model,
      depigmentation was introduced by gene gun vaccination with eukaryotic expression
      plasmids encoding melanocyte differentiation antigens. Inclusion of human and
      mouse-derived inducible HSP70 in the vaccination protocol significantly increased
      and accelerated depigmentation in this model, accompanied by the induction of
      prolonged humoral responses to HSP70. Cytotoxicity toward targets loaded with a
      K(b)-restricted tyrosinase-related protein 2-derived peptide correlated with
      depigmentation. The data presented strongly support a role for HSP70i in
      progressive depigmentation in vivo.

PMID- 18337836
TI  - FR255734, a humanized, Fc-Silent, Anti-CD28 antibody, improves psoriasis in the
      SCID mouse-psoriasis xenograft model.
AB  - In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using
      the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we
      report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody
      (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis
      plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal
      injections of FR255734 at 10, 3, and 1-mg kg(-1) doses. Groups treated with doses
      of 10 and 3 mg kg(-1) had significant thinning of the epidermis and reduced HLA
      DR-positive lymphocytic infiltrates. The length of the rete pegs changed from
      415.2+/-59.6 to 231.4+/-40.4 microm (P<0.005) in the 10-mg kg(-1) group, and from
      323.4+/-69.6 to 237.5+/-73.6 microm in the 3-mg kg(-1) group (P=0.002). Positive
      controls treated with CTLA4-Ig and cyclosporine had significant histological
      improvement, whereas plaques treated with saline and isotype controls (human and
      mouse IgG2) remained unchanged. In vitro studies have shown that FR255734
      effectively blocked T-cell proliferation and proinflammatory cytokine production.
      These observations warrant studies to evaluate the efficacy of FR255734 in human
      autoimmune diseases.

PMID- 18337837
TI  - Lack of functionally active Melan-A(26-35)-specific T cells in the blood of HLA
      A2+ vitiligo patients.
AB  - Vitiligo, a skin disorder characterized by the spontaneous destruction of
      melanocytes, is believed to be of autoimmune origin. We investigated the presence
      and functionality of CD8(+) T-cells specific for the melanocyte-associated
      antigens Melan-A, gp100, tyrosinase, and TRP-2 in the blood of HLA-A2(+) vitiligo
      patients. We enumerated antigen-specific CD8(+) T cells by major
      histocompatibility complex multimer staining directly ex vivo, as well as after 9
      days of in vitro stimulation and assessed IFN-gamma secretion by enzyme-linked
      immunospot (Elispot) assay. Tyrosinase-, gp100-, or TRP-2-specific CD8(+) T cells
      could not be identified in the peripheral blood of individuals with vitiligo.
      Although Melan-A-specific T cells were detectable at levels comparable to Flu-MP
      specific T cells by multimer staining, these lymphocytes did not express the skin
      homing receptor cutaneous lymphocyte antigen, were phenotypically naive
      (CD45RA(+)), and were unresponsive in the IFN-gamma Elispot assay, suggesting
      that they are unlikely to be involved in the etiopathogenesis of vitiligo.

PMID- 18337838
TI  - Targeting gene expression to cones with human cone opsin promoters in recombinant
      AAV.
AB  - Specific cone-directed therapy is of high priority in the treatment of human
      hereditary retinal diseases. However, not much information exists about the
      specific targeting of photoreceptor subclasses. Three versions of the human red
      cone opsin promoter (PR0.5, 3LCR-PR0.5 and PR2.1), and the human blue cone opsin
      promoter HB569, were evaluated for their specificity and robustness in targeting
      green fluorescent protein (GFP) gene expression to subclasses of cones in the
      canine retina when used in recombinant adeno-associated viral vectors of serotype
      5. The vectors were administered by subretinal injection. The promoter PR2.1 led
      to most effective and specific expression of GFP in the long- and medium
      wavelength-absorbing cones (L/M cones) of normal and diseased retinas. The PR0.5
      promoter was not effective. Adding three copies of the 35-bp LCR in front of
      PR0.5 lead to weak GFP expression in L/M cones. The HB569 promoter was not
      specific, and GFP was expressed in a few L/M cones, some rods and the retinal
      pigment epithelium. These results suggest that L/M cones, the predominant class
      of cone photoreceptors in the retinas of dogs and most mammalian species can be
      successfully targeted using the human red cone opsin promoter.

PMID- 18337839
TI  - Site-specific gene modification by oligodeoxynucleotides in mouse bone marrow
      derived mesenchymal stem cells.
AB  - Synthetic oligodeoxynucleotides (ODNs) had been employed in gene modification and
      represent an alternative approach to 'cure' genetic disorders caused by
      mutations. To test the ability of ODN-mediated gene repair in bone marrow-derived
      mesenchymal stem cells (MSCs), we established MSCs cell lines with stably
      integrated mutant neomycin resistance and enhanced green fluorescent protein
      reporter genes. The established cultures showed morphologically homogenous
      population with phenotypic and functional features of mesenchymal progenitors.
      Transfection with gene-specific ODNs successfully repaired targeted cells
      resulting in the expression of functional proteins at relatively high frequency
      approaching 0.2%. Direct DNA sequencing confirmed that phenotype change resulted
      from the designated nucleotide correction at the target site. The position of the
      mismatch-forming nucleotide was shown to be important structural feature for ODN
      repair activity. The genetically corrected MSCs were healthy and maintained an
      undifferentiated state. Furthermore, the genetically modified MSCs were able to
      engraft into many tissues of unconditioned transgenic mice making them an
      attractive therapeutic tool in a wide range of clinical applications.

PMID- 18337840
TI  - Keeping an eye on clinical trials in 2008.

PMID- 18337841
TI  - RNA-loaded CD40-activated B cells stimulate antigen-specific T-cell responses in
      dogs with spontaneous lymphoma.
AB  - Cell-based vaccination strategies to induce functional tumor-specific T cells in
      cancer patients have focused on using autologous dendritic cells. An alternative
      approach is to use RNA-loaded CD40 activated B cells (CD40-B) that are highly
      efficient antigen-presenting cells capable of priming naive T cells, boosting
      memory T-cell responses and breaking tolerance to tumor antigens. The use of
      tumor RNA as the antigenic payload allows for gene transfer without viruses or
      vectors and permits major histocompatibility complex (MHC)-independent, multiple
      antigen targeting. Here, we use CD40L transfected K562 cells to generate
      functional CD40-B cells from the peripheral blood of humans and dogs. Testing of
      RNA-loaded CD40-B cells in dogs allows not only for its development in veterinary
      medicine but also for determination of its safety and efficacy in a large animal
      model of spontaneous cancer prior to initiation of human clinical trials. We
      found that CD40-B cells from healthy humans, healthy dogs and tumor-bearing dogs
      express increased levels of immune molecules such as MHC and CCR7. Moreover, RNA
      loaded CD40-B cells induce functional, antigen-specific T cells from healthy dogs
      and dogs with lymphoma. These findings pave the way for immunotherapy trials
      using tumor RNA-loaded CD40-B cells to stimulate antitumor immunity in a large
      animal model of spontaneous neoplasia.

PMID- 18337842
TI  - [The personal experience].

PMID- 18337843
TI  - [Late, but good].

PMID- 18337844
TI  - [Powerful leadership].

PMID- 18337845
TI  - [Is the latest always the best?].

PMID- 18337846
TI  - [Better reporting of epidemiologic research].

PMID- 18337847
TI  - [Cervical cancer after 10 years of nationally coordinated screening].
AB  - BACKGROUND: A cervical cancer screening programme has been operating on a
      national level since 1995. Women aged 25-69 years who have not had a Pap smear in
      the previous 3-year period, are recommended by letter to contact a doctor and
      have a smear taken. The aims of the programme are a more rational use of tests
      and to decrease the incidence and mortality of the disease. MATERIAL AND METHODS:
      Trends in incidence and mortality of cervical cancer are studied by data from the
      national cancer registry, which also collects data on individual smears. RESULTS:
      From the period 1990-94 to the period 2000-04 the age-adjusted incidence rate per
      1,000, 000 person-years decreased from 127 to 95, the corresponding rate for
      squamous carcinomas decreased from 102 to 70. The age-adjusted mortality rate
      decreased from 38 to 25. Number of tests decreased from 542,666 in 1994 to 486
      118 in 2004. The proportion of women aged 25-69 years who had a test taken during
      the last four years, increased from 72.4% in 1995 to 78.3% in 2004.
      INTERPRETATION: Implementation of a nationally coordinated cervical cancer
      screening programme has contributed to a favourable development of the disease
      (lower incidence and mortality) and a more rational use of tests. Continued
      efforts are needed to achieve the goals of the programme.

PMID- 18337848
TI  - [What is the duration of normal labour?].
AB  - BACKGROUND: A third of all pregnant women in Norway have slow progress of labour,
      and almost as many have their labours augmented. Midwives and obstetricians do
      not agree about the duration of normal labour. The aim of the present study was
      to review textbooks, guidelines and studies to assess how the 1 st and 2 nd
      stages of labour were defined and how duration of the stages was described.
      MATERIAL AND METHOD: Syllabus lists, websites and on-line bookstores were
      searched for textbooks and guidelines and the databases MEDLINE and MIDIRS were
      searched for scientific studies published in 1995 and later. Additional studies
      were found in the reference lists of the studies identified. RESULTS: Eight
      textbooks, 7 guidelines and 9 studies were found to be relevant. Definitions of
      birth onset, its phases and duration varied; i.e. onset of the latent phase of
      the 1 st stage of labour and onset of the 2 nd stage. Onset of the active phase
      was defined almost identically at a cervical dilatation of 3-4 cm. Some textbooks
      and guidelines divided the 2 nd stage in two phases: the latent and active phase.
      The end of the 2 nd stage was always defined as the birth of the baby.
      INTERPRETATION: Definition of a normal duration of labour lacks scientific
      support. As many women are assessed to have slow progress of labour, the duration
      of labour should be systematically recorded. Prospective studies are needed on
      labour duration, the consequences of prolonged labour and the appropriate timing
      for intervention.

PMID- 18337849
TI  - [Measurement of methylmalonic acid, homocysteine and methionine in cobalamin and
      folate deficiencies and homocysteinuria].
AB  - BACKGROUND: Deficiencies of cobalamin (vitamin B12) or folate are common
      conditions that predispose for anemia and chronic diseases. An elevated
      concentration of methylmalonic acid in plasma/serum is an indicator of cobalamin
      deficiency, whereas an increased concentration of total homocysteine in plasma
      occurs with deficiency of both cobalamin and folate. The biomarkers methylmalonic
      acid and homocysteine are therefore complementary, and the combination is often
      requested when conventional tests fail to provide an unambiguous diagnosis.
      MATERIAL AND METHODS: This article summarizes publications, retrieved through
      Medline, describing novel strategies for laboratory diagnostics of cobalamin and
      folate deficiencies. RESULTS AND INTERPRETATION: Adverse health effects of food
      fortification and uncritical supplementation with folic acid are explanations for
      a renewed interest in individual diagnosis of B-vitamin deficiency.
      Interpretation of methylmalonic acid and homocysteine test results requires
      knowledge of kidney function, as renal failure causes an increase in the
      concentrations of both metabolites. Homocystinuria is a condition that also
      causes increased levels of plasma homocysteine. This condition is an inborn error
      with a higher prevalence (1 : 6400) than previously recognized; which usually
      responds favourably to homocysteine-lowering therapy. Patients with
      homocysteinuria have high levels of methionine in plasma and knowledge of plasma
      methionine concentration may therefore distinguish these patients from those with
      conditions like B-vitamin deficiencies or renal failure, which are accompanied by
      normal or low to normal methionine concentrations. Complementarity, logistics,
      small sample volumes and costs therefore favour a combined analysis of
      methylmalonic acid, homocysteine and methionine in a single sample. Such an
      approach also allows assessment of cobalamin status in small volume capillary
      blood samples drawn from newborns and infants.

PMID- 18337850
TI  - [The health food product Noni--does marketing harmonize with the current status
      of research?].
AB  - BACKGROUND: Norwegian cancer patients frequently use Noni. The objective of this
      study was to find out whether the way noni is marketed in Norway and the health
      claims made about the product harmonize with current scientific knowledge of its
      benefits/adverse effects. MATERIAL AND METHODS: An overview of medical research
      on noni was obtained from three databases. Web sites for private persons and for
      companies that sell noni in Norway were examined. Books, pamphlets etc. from a
      company specializing in selling information material about noni, were also
      examined. RESULTS: 48 scientific articles were included in the study, but none of
      these were clinical studies of humans. Several pharmacological effects of noni
      have been shown in vitro and in animal models (e.g., increased survival for
      animals with cancer). Information material describes noni as a health-promoting
      product that patients with most diseases will benefit from. Noni is to a great
      extent sold by multi-level marketing, but is also commonly sold by health food
      stores. INTERPRETATION: There is no scientific basis for claiming that patients
      will benefit from using noni for any diseases. The way this product is sold has
      several worrying aspects.

PMID- 18337851
TI  - [Stroke--endovascular treatment methods].
AB  - BACKGROUND: Over the last years, endovascular treatment (intra-arterial
      thrombolysis, thrombembolectomy, angioplasty or intracranial stenting) has been
      used to treat acute ischemic stroke. The aim of this article is to discuss
      endovascular treatment of stroke, based on 3 cases and the present knowledge in
      this field. MATERIAL AND METHODS: Three patients presented with symptoms of acute
      stroke and received endovascular treatment. The cases are discussed with
      reference to literature identified in Pubmed. RESULTS AND INTERPRETATION: A
      prospective randomized study of intraarterial thrombolysis within 6 hours of
      symptom debut has been published, but there is no randomized study on mechanical
      thrombectomy in acute stroke. Several phase II studies have however shown
      promising results. The patients presented here illustrate the need for urgent
      diagnosis and collaboration between various specialities when neurointervention
      is considered. Patients with symptomatic intracranial stenosis, already on anti
      platelet therapy, should be evaluated for angioplasty with or without stenting.
      Patients with acute ischemic stroke who have not had effect of intravenous
      thrombolysis, or have been admitted too late to receive such treatment, should be
      assessed quickly for mechanical thrombectomy, intra-arterial thrombolysis or
      both.

PMID- 18337852
TI  - [Anaesthetics and breast feeding].
AB  - Many women undergo anaesthetic procedures related to childbirth or during the
      period of lactation. Most anaesthetic drugs are lipophilic and are thus excreted
      into breast milk. This article summarises available knowledge regarding
      anaesthetics, their excretion into breast milk and possible effects on the
      suckling infant. The consequences of such an exposure are discussed in terms of
      whether breast-feeding should be allowed or not after anaesthetic procedures.

PMID- 18337854
TI  - [Cochlear implants and specific language difficulties].

PMID- 18337855
TI  - [A new study of chronic lymphatic leukemia in Norway].

PMID- 18337857
TI  - Glucosamine in the treatment of osteoarthritis.

PMID- 18337858
TI  - [German medicine seen from KZ Buchenwald].

PMID- 18337860
TI  - [Vietnamese orthopedics].

PMID- 18337863
TI  - Interpolation of the spectral responsivity of silicon photodetectors in the near
      ultraviolet.
AB  - We improve the methods used to interpolate the responsivity of unbiased silicon
      photodetectors in the near-ultraviolet region. This improvement is achieved by
      the derivation of an interpolation function for the quantum yield of silicon and
      by consideration of this function in the interpolation of the internal quantum
      efficiency of photodiodes. The calculated quantum-yield and spectral-responsivity
      values are compared with measurement results obtained by the study of a silicon
      trap detector and with values reported by other research groups. The comparisons
      show agreement with a standard deviation of 0.4% between our measured and modeled
      values for both the quantum yield and the spectral responsivity within the
      wavelength region from 260 to 400 nm. The proposed methods thus extend the
      predictability of the spectral responsivity of silicon photodetectors to the
      wavelength region from 260 to 950 nm. Furthermore, an explanation is proposed for
      the change in the spectral responsivity of silicon photodiodes that is due to UV
      radiation. In our improved quantum efficiency model the spectral change can be
      accounted for completely by the adjustment of just one parameter, i.e., the
      collection efficiency near the SiO(2)/Si interface.

PMID- 18337864
TI  - Recording high-dispersion spherical holographic gratings in a modified Rowland
      mounting by use of a multimode deformable mirror.
AB  - To reduce the uncorrected higher-order aberrations for holographic gratings
      requiring an extreme dispersion, we have modified the Rowland mounting by moving
      the recording laser sources away from the grating. Then, with a multimode
      deformable plane mirror to record the grating, the correction of all the
      aberrations up to the fourth order inclusive is found sufficient to obtain a high
      quality image. Applied to the FUSE-LYMAN grating, with a groove density of as
      much as 5740 grooves/mm, for which a resolution of 30,000 was required, this new
      recording device produces a resolution from 139,000 to 222,000 over the spectral
      range.

PMID- 18337865
TI  - Contrast in the evanescent near field of lambda/20 period gratings for
      photolithography.
AB  - Light propagation through gratings with periods as small as lambda/20 is
      investigated computationally by use of the multiple multipole method in two
      dimensions. High image contrast is evident close to the grating. Strong
      evanescent decay of the high spatial frequency components is observed with the
      region of high contrast shrinking linearly as the period of the grating is
      decreased. Simulations were performed for TE and TM polarizations with the TM
      polarization providing the dominant contrast compared with TE, which is strongly
      attenuated owing to the polarizing effect of the gratings. These results show
      good promise for optical contact lithography in the evanescent near field of a
      shadow mask to attain feature sizes smaller than lambda/20.

PMID- 18337866
TI  - Optical levitation particle delivery system for a dual beam fiber optic trap.
AB  - We combine a radiation-pressure-based levitation system with a dual fiber, laser
      trapping system to demonstrate the potential of delivering single particles into
      the fiber trap. The forces versus position and the trajectory of the particle
      subjected to the laser beams are examined with an enhanced ray optics model. A
      sequence of video images taken from the experimental apparatus demonstrates the
      principle of particle delivery, trapping, and further manipulation.

PMID- 18337867
TI  - Aberrations from a prism and a grating.
AB  - Formulas for the wave aberrations introduced into a beam by a prism or a plane
      grating are derived from the theory of plane symmetric systems. Emphasis is made
      on the field-dependent aberrations.

PMID- 18337868
TI  - Optical configuration and color-representation range of a variable-pitch dot
      matrix holographic printer.
AB  - The optical system configuration and design of a dot matrix holographic printer
      that can create image grating pixels of variable size, arbitrary pitch, and
      discretionary angle on a photoresist plate are presented. With the capability to
      vary spot size, grating orientation, and grating pitch on the fly, this newly
      developed holographic printer can apply a prespecified color at each specific
      viewing angle. Diffractive images with various visual effects and the wide color
      range that are possible by use of this system are examined in detail.

PMID- 18337869
TI  - High-resolution laser speckle correlation for displacement and strain
      measurement.
AB  - A laser speckle correlator with high optical magnification is presented, and its
      performance in the measurement of strain is demonstrated experimentally. Two
      separated areas on a test specimen are illuminated with laser beams, and
      displacements of each area are measured by performance of laser speckle
      correlation on successive magnified images. The interplay of magnification, lens
      aperture, surface roughness, pixel spacing on the CCD array sensor, and the
      attainable precision of correlation are investigated theoretically and
      experimentally. Resolutions that are usually considered accessible only to
      interferometric techniques are achieved: displacement resolutions of less than 50
      nm and strain measurements of less than 10 microstrain across distances of the
      order of 10 mm are demonstrated. At high magnification, speckle decorrelation due
      to out-of-plane displacement becomes a stringent restriction, and surface height
      correlation effects may limit speckle contrast and broaden speckle correlation
      peaks.

PMID- 18337870
TI  - Comparison of Kretschmann-Raether angular regimes for measuring changes in bulk
      refractive index.
AB  - We compare two angular regimes for the measurement of changes in the real
      refractive index of bulk fluid analytes. The measurements are based on the use of
      the Kretschmann-Raether configuration to sense a change in reflectivity with
      index. Specifically, we numerically simulate the relative sensitivities of the
      total internal reflection (TIR) and the surface-plasmon resonance (SPR) regimes.
      For a fixed-angle apparatus, the method that gives the greatest change in
      reflectivity varies with metal film thickness. For films thicker than the skin
      depth, the SPR regime is the most sensitive to index changes. For thinner films,
      however, the TIR angle is then dominant, with increases in sensitivity on the
      order of 75% for 10-nm gold or silver media.

PMID- 18337871
TI  - Three-dimensional shape measurement of a diffusing surface by use of a
      femtosecond amplifying optical Kerr gate.
AB  - We propose a system for three-dimensional (3D) shape measurement of a diffusing
      surface by use of a previously developed femtosecond amplifying optical Kerr gate
      (fs-amp OKG). The system has an opening time of 459 fs and a maximum
      transmittance of 185%. It also provides good 3D imaging performance: a transverse
      imaging resolution of 70 microm, a depth resolution of 100 microm, and a
      positioning accuracy of 5.9 microm in depth. It is found that the optical Kerr
      effect and the amplification process in the fs-amp OKG do not cause the quality
      of a time-resolved image to deteriorate. We prove the effectiveness of the
      proposed system by measuring the shapes of completely diffusing objects with
      stepped and spherical surfaces.

PMID- 18337872
TI  - Wave-front sensing with a sampling field sensor.
AB  - We present a new type of optical wave-front sensor: the sampling field sensor
      (SFS). The SFS attempts to solve the problem of real-time optical phase
      detection. It has a high space-bandwidth product and can be made compact and
      vibration insensitive. We describe a particular implementation of this sensor and
      compare it, through numerical simulations, with a more mature technique based on
      the Shack-Hartmann wave-front sensor. We also present experimental results for
      SFS phase estimation. Finally, we discuss the advantages and drawbacks of this
      SFS implementation and suggest alternative implementations.

PMID- 18337873
TI  - Design and experimental characterization of a high-resolution instrument for
      measuring the extreme-UV absorption of laser plasmas.
AB  - The performances of a spectrometer for the observation of laser plasma absorption
      with high spectral and spatial resolution are described. Aspherical optics are
      used to correct the astigmatism in an extended spectral region. In this way only
      a small portion of the absorbing medium is probed, thus giving a good selection
      of the ionization stage acting as the absorption. Moreover, in the focal plane
      the plasma emission from the absorbing medium is spatially separated from the
      probe beam, with a consequent enhancement of the measurement sensitivity. The
      predicted optical performances from a ray tracing are compared with experimental
      observations for both spectral and spatial resolution.

PMID- 18337874
TI  - Calibration of a deformable mirror and Strehl ratio measurements by use of phase
      diversity.
AB  - Calibration experiments with a bimorph mirror are presented. Phase-diversity wave
      front sensing is used for measuring the control matrix, nulling wave-front errors
      in the optical setup, including the mirror, and measuring Strehl ratios and
      residual higher-order aberrations. The Strehl ratio of the calibrated system is
      measured to be 0.975, corresponding to 1/40 wave rms in the residual wave front.
      The conclusion is that a phase-diversity wave-front sensor is easier to install
      and use than interferometers and can replace them in optical setups for testing
      adaptive optics systems.

PMID- 18337875
TI  - Surface profilometry with laser-diode optical feedback interferometer outside
      optical benches.
AB  - A simple and robust interferometer with a laser diode subject to optical feedback
      from the interferometer is presented for surface testing of a spherical mirror.
      The fringe phase can be locked by the optical feedback within less than 0.2pi
      (peak-to-valley value) even when the interferometer is placed on a wooden table.
      The fringe locking is caused by the change of lasing wavelength that suppresses
      the net phase change to be much less than 2pi. The locked fringe pattern with
      spatial carriers can be analyzed by a fringe analyzer at a video rate, and the
      measurement results of the spherical mirror showed the same result as on an
      optical bench.

PMID- 18337876
TI  - High-accuracy fourier transform interferometry, without oversampling, with a 1
      bit analog-to-digital converter.
AB  - We demonstrate a new technique for performing accurate Fourier transform
      interferometry with a 1-bit analog-to-digital (AD) converter that does not
      require oversampling of the interferogram, unlike in other 1-bit coding schemes
      that rely on delta-sigma modulation. Sampling aims at locating the intersections
      {z(i)} of the modulation term s(z) of the interferogram and a reference sinusoid
      r(z) = A cos(2pif(r)z), where z is the optical path difference. A new
      autocorrelation-based procedure that includes the accurate recovery of the
      equally sampled amplitude representation {s(k)} of s(z) from {z(i)} is utilized
      to calculate the square of the emission spectrum of the light source (sample).
      The procedure is suitable for interferograms that are corrupted with additive
      noise. Sinusoid-crossing sampling satisfies the Nyquist sampling criterion, and a
      z(i) exists within each sampling interval Delta = 1/2f(r), if A >or= |s(z)| for
      all z, and f(r) >or= f(c), where f(c) is the highest frequency component of s(z).
      By locating a crossing at an accuracy of 1 part in 2(16), we determine the
      multimode spectrum of an argon-ion laser with a 1-bit AD converter that performs
      like a 13-bit amplitude-sampling AD converter.

PMID- 18337877
TI  - Heterodyne temporal speckle-pattern interferometry.
AB  - In temporal speckle-pattern interferometry deformation information is extracted
      by a Fourier transform technique from the speckle pattern that is recorded over a
      period of time as the object is deformed. A limitation of the experimental
      arrangements reported to date is that the direction of the deformation cannot be
      determined. We propose removing this limitation by using the heterodyne
      principle. Some experimental results that were obtained by use of a rotating half
      wave-plate frequency shifter are presented.

PMID- 18337878
TI  - Interferometer for use in wave-front testing with a cross slit.
AB  - A simple and novel interferometric setup for wave-front testing that uses a cross
      slit is described. In this method, the test beam illuminates a cross slit placed
      at the front focal plane of a Fourier lens. It selects two orthogonal slices from
      the test beam, and the interference of these two beams is observed at a slightly
      defocused plane near the back focal plane. Fringes of different conical forms
      (circular, elliptical, or hyperbolic) so obtained can be used for testing a
      coherent wave front in general. The theory, supported by some experimental
      results, is presented. An application of the method to the study of the nature of
      asymmetry in the beam profile of a semiconductor diode laser beam is
      demonstrated.

PMID- 18337879
TI  - Guided wave acousto-optic and electro-optic tunable filter designs with relaxed
      beam-splitter requirements.
AB  - New designs for acousto-optic tunable filters and electro-optic tunable filters
      with the Mach-Zehnder configuration are proposed. The new designs differ from
      conventional designs in three respects: (1) polarizing beam splitters are not
      required, (2) the optical path difference for the waveguides between the beam
      splitters is a half-wavelength, and (3) the relative positions of the
      polarization coupling regions in the two waveguides are displaced in the
      propagation direction by half of the spatial period of the perturbation
      responsible for the coupling. Because the new designs provide an additional
      degree of freedom in achieving the required beam-splitter performance, they are
      expected to be much easier to fabricate than conventional filter designs with
      polarizing beam splitters.

PMID- 18337880
TI  - Optical contrast in apertureless microscopy.
AB  - We report on optical image contrast for a specific apertureless near-field
      optical microscope. We demonstrate that the main part of the optical image's
      contrast results from the sample's topography. The coupling mechanism is
      analyzed, and we show that the microscope can be regarded as an interferometer
      that sensitively detects near-field components. However, in the basic
      configuration the reference field of the interferometer is coupled to the
      topography. Finally, it is demonstrated that, by controlling the phase of the
      reference field, one can largely decorrelate the optical image from the
      topography.

PMID- 18337881
TI  - Narrow-band interference filters with unconventional spacer layers.
AB  - Classical narrow-band interference dielectric filters with all-dielectric
      reflectors have quarter-wave stacks separated by a half-wave thickness (or a
      multiple-) spacer layer. These filters are essentially Fabry-Perot filters; hence
      the theory developed for those filters applies in full. The theory of narrow-band
      interference dielectric filters with unconventional spacer layers is presented.
      This spacer layer consists of two different materials. The optical features of
      these filters are compared with the features of Fabry-Perot filters. The
      influence of the errors of the layers on spectral characteristics is analyzed.
      The theory presented can be applied to any spectral range as well as to any thin
      film material, including absorbing and nonlinear materials.

PMID- 18337882
TI  - Simple recurrence matrix relations for multilayer anisotropic thin films.
AB  - Generalized Abeles relations for one anisotropic thin film [E. Cojocaru, Appl.
      Opt. 36, 2825-2829 (1997)] are developed for light propagation from an isotropic
      medium of incidence (with refractive index n(0)) within a multilayer anisotropic
      thin film coated onto an anisotropic substrate. An immersion model is used for
      which it is assumed that each layer is imaginatively embedded between isotropic
      gaps of zero thickness and refractive index n(0). This model leads to simple
      expressions for the resultant transmitted and reflected electric field amplitudes
      at interfaces. They parallel the Abeles recurrence relations for layered
      isotropic media. These matrix relations include multiple reflections while they
      deal with total fields. They can be applied directly to complex stacks of
      isotropic and anisotropic thin films.

PMID- 18337883
TI  - Preservation of far-UV aluminum reflectance by means of overcoating with C60
      films.
AB  - Thin films of C(60) were investigated as protective coatings of Al films to
      preserve their far-UV (FUV) reflectance by inhibition or retardation of their
      oxidation. Two methods were used for the overcoating of Al films with
      approximately one monolayer of C(60): (1) deposition of a multilayer film
      followed by temperature desorption of all but one monolayer and (2) direct
      deposition of approximately one-monolayer film. We exposed both types of sample
      to controlled doses of molecular oxygen and water vapor and measured their FUV
      reflectance before and after exposure to evaluate the achieved protection on the
      Al films. The whole process of sample preparation, reflectance measurement,
      sample heating, and oxidation was made without breaking vacuum. Results show that
      a C(60) monolayer protected Al from oxidation to some extent, although FUV
      reflectance of unprotected Al films was never exceeded. FUV optical constants of
      C(60) films and the FUV reflectance of the C(60) film as deposited and as a
      function of exposure to O(2) were also measured.

PMID- 18337884
TI  - High-rate automated deposition system for the manufacture of complex multilayer
      coatings.
AB  - A previously described automated thin-film deposition system based on rf
      magnetron sputtering could deposit quite complex optical multilayer systems with
      good precision and with no one in attendance [Sullivan and Dobrowolski, Appl.
      Opt. 32, 2351-2360 (1993)]. However, the deposition rate was slow, and the
      uniform area on the substrate was limited. We describe an ac-magnetron sputtering
      process in which the same deposition accuracy has been combined with
      significantly better film uniformity and a fivefold or sevenfold increase in the
      deposition rate. This makes the equipment of commercial interest. Experimental
      results are presented for several difficult coating problems.

PMID- 18337885
TI  - Trichroic prism assembly for separating and recombining colors in a compact
      projection display.
AB  - A trichroic prism assembly design, believed to be new, is proposed and
      demonstrated. This new design has the advantages of low s- and p-polarization
      dependence in the reflectance spectra of the optical coatings. Hence it can be
      used for both color separation and color recombination with polarization change.
      This new trichroic prism assembly is especially useful in a compact color
      projector employing reflective liquid-crystal light valves.

PMID- 18337886
TI  - Unbalanced versus balanced operation in an optical coherence tomography system.
AB  - The choice of a balanced optical coherence tomography (OCT) configuration versus
      an unbalanced OCT configuration with optimized reference-arm attenuation is
      discussed. The choice depends on the receiver noise, the fiber-end reflection R,
      and the power to the object. When OCT is used to investigate biological tissue an
      equivalent R? can be evaluated as the compound reflected light from tissue. In
      this case an additional parameter has to be considered: the confocal optical
      sectioning interval of the OCT system.

PMID- 18337887
TI  - Photon statistics and correlation analysis of ultraweak light originating from
      living organisms for extraction of biological information.
AB  - Ultraweak photon emission phenomena in the visible to near-IR region, originating
      from biological organisms, are known. This biophoton emission is generated during
      metabolic processes and constitutes physiological information. We investigated a
      technique for characterizing the optical radiation field based on photon
      statistics and correlation analysis to extract information on regulation
      processes in biochemical reactions and their interactions. We developed the
      system based on the time-interval measurement of photoelectrons in a photon
      counting region and employed data processing with a nonstationary optical field
      with correction for the correlative properties of the photomultiplier dark
      current. We analyzed biophoton emission from cellular slime mold (Dictyosterium
      discoideum) and observed the characteristic variation of this organism's super
      Poisson statistics during the developmental process.

PMID- 18337888
TI  - Principle of pattern-signature synthesis and analysis based on double optical
      correlations.
AB  - Pattern-recognition problems for which patterns cannot be recognized directly but
      by their attitudes and/or behaviors is addressed. To analyze these attitudes,
      pattern signatures are generated from picture sequences. Two complementary
      signature synthesis algorithms are presented. The architecture is made up of two
      cascaded correlators. The first is used to create the signatures and the second
      to classify them. We focus our analysis on the case of optical implementations.
      Illustrations are given in the case of face recognition by attitudes (multisensor
      in the optronic imaging range) and moving-target recognition by behavior (in the
      radar imaging range).

PMID- 18337889
TI  - Optical BEAMTAP beam-forming and jammer-nulling system for broadband phased-array
      antennas.
AB  - We present an approach to receive-mode broadband beam forming and jammer nulling
      for large adaptive antenna arrays as well as its efficient and compact optical
      implementation. This broadband efficient adaptive method for true-time-delay
      array processing (BEAMTAP) algorithm decreases the number of tapped delay lines
      required for processing an N-element phased-array antenna from N to only 2,
      producing an enormous savings in delay-line hardware (especially for large
      broadband arrays) while still providing the full NM degrees of freedom of a
      conventional N-element time-delay-and-sum beam former that requires N tapped
      delay lines with M taps each. This allows the system to adapt fully and optimally
      to an arbitrarily complex spatiotemporal signal environment that can contain
      broadband signals of interest, as well as interference sources and narrow-band
      and broadband jammers--all of which can arrive from arbitrary angles onto an
      arbitrarily shaped array--thus enabling a variety of applications in radar,
      sonar, and communication. This algorithm is an excellent match with the
      capabilities of radio frequency (rf) photonic systems, as it uses a coherent
      optically modulated fiber-optic feed network, gratings in a photorefractive
      crystal as adaptive weights, a traveling-wave detector for generating time delay,
      and an acousto-optic device to control weight adaptation. Because the number of
      available adaptive coefficients in a photorefractive crystal is as large as
      10(9), these photonic systems can adaptively control arbitrarily large one- or
      two-dimensional antenna arrays that are well beyond the capabilities of
      conventional rf and real-time digital signal processing techniques or alternative
      photonic techniques.

PMID- 18337890
TI  - Wiener-like correlation filters.
AB  - We introduce a new, to our knowledge, design for a Wiener-like correlation
      filter, which consists of cascading a phase-only filter (POF) with a
      photorefractive Wiener-like filter. Its performance is compared with that of the
      POF and the Wiener correlation filter (WCF). Correlation results show that for
      intermediate and higher levels of noise this correlation filter has a peak-to
      noise ratio that is larger than that of either the POF or the WCF while still
      preserving a correlation peak that is almost as high as that of the POF.

PMID- 18337891
TI  - White-light optical implementation of the fractional fourier transform with
      adjustable order control.
AB  - An optical implementation of the fractional Fourier transform (FRT) with
      broadband illumination is proposed by use of a single imaging element, namely, a
      blazed diffractive lens. The setup displays an achromatized version of the FRT of
      order P of any two-dimensional input function. This fractional order can be tuned
      continuously by shifting of the input along the optical axis. Our compact and
      flexible configuration is tested with a chirplike input signal, and the good
      experimental results obtained support the theory.

PMID- 18337892
TI  - Pulsed digital holographic interferometry with 694- and 347-nm wavelengths.
AB  - A method for deformation analysis and shape measurement based on digital
      holography is presented. Two wavelengths, 694 and 347 nm, are used. The object is
      illuminated with the two wavelengths at the same time, and digital holograms are
      recorded on a CCD chip. The information corresponding to the two wavelengths is
      separated in the Fourier domain, and the phase corresponding to the wave fronts
      is calculated. By recording holograms with two different wavelengths at the same
      time, we can get measurements of deformations or shape with different
      sensitivities. Experimental results are presented.

PMID- 18337893
TI  - Generalized wave-front reconstruction algorithm applied in a Shack-Hartmann Test.
AB  - A generalized numerical wave-front reconstruction method is proposed that is
      suitable for diversified irregular pupil shapes of optical systems to be
      measured. That is, to make a generalized and regular normal equation set, the
      test domain is extended to a regular square shape. The compatibility of this
      method is discussed in detail, and efficient algorithms (such as the Cholesky
      method) for solving this normal equation set are given. In addition, the authors
      give strict analyses of not only the error propagation in the wave-front estimate
      but also of the discretization errors of this domain extension algorithm.
      Finally, some application examples are given to demonstrate this algorithm.

PMID- 18337894
TI  - Communication theoretic image restoration for binary-valued imagery.
AB  - We present a new image-restoration algorithm for binary-valued imagery. A trellis
      based search method is described that exploits the finite alphabet of the target
      imagery. This algorithm seeks the maximum-likelihood solution to the image
      restoration problem and is motivated by the Viterbi algorithm for traditional
      binary data detection in the presence of intersymbol interference and noise. We
      describe a blockwise method to restore two-dimensional imagery on a row-by-row
      basis and in which a priori knowledge of image pixel correlation structure can be
      included through a modification to the trellis transition probabilities. The
      performance of the new Viterbi-based algorithm is shown to be superior to Wiener
      filtering in terms of both bit error rate and visual quality. Algorithmic choices
      related to trellis state configuration, complexity reduction, and transition
      probability selection are investigated, and various trade-offs are discussed.

PMID- 18337895
TI  - Optical tomographic microscope for quantitative imaging of phase objects.
AB  - We describe a tomographic microscope, for imaging phase objects, that makes use
      of the transport-of-intensity equation to estimate the phase of the transmitted
      light through the object. The wave-front data from optical fibers are
      reconstructed with an algorithm that incorporates correction for the ray bending.
      The reconstructed refractive-index cross sections of the fibers are found to be
      in agreement with the available values specified in the catalogs.

PMID- 18337896
TI  - Robust spatiotemporal quadrature filter for multiphase stepping.
AB  - A robust algorithm for phase recovery from multi-phase-stepping images is
      presented. This algorithm is based on the minimization of an energy (cost)
      functional and is equivalent to the simultaneous application of a fixed temporal
      quadrature filter and a spatial adaptive quadrature filter to the phase-stepping
      pattern ensemble. The algorithm, believed to be new, is specially suited for
      those applications in which a large number of phase-stepping images may be
      obtained, e.g., profilometry with a computer-controlled fringe projector. We
      discuss the selection of parameter values and present examples of its performance
      in both synthetic and real image sequences.

PMID- 18337897
TI  - Analysis and characterization of alignment for free-space optical interconnects
      based on singular-value decomposition.
AB  - We propose a theoretical method to analyze and characterize the alignment of
      optical systems by using a singular-value decomposition (SVD) technique. One
      application of this method is to identify critical parameters for alignment
      systematically during alignment of two-dimensional device arrays. Another example
      application is to characterize the sensitivity or the accuracy of the
      misalignment-detection capability by evaluation of the singular values of optical
      systems. The information obtained through SVD-based techniques yields critical
      insights into the analysis of alignment.

PMID- 18337898
TI  - Evanescent coupling in magneto-optical and phase-change disk systems based on the
      solid immersion lens.
AB  - Results of numerical computations pertaining to evanescent wave coupling for near
      field magneto-optical and phase-change disks based on the concept of the solid
      immersion lens are presented. We investigated the relation between the coupling
      efficiency and the width of the air gap in terms of the throughput of the
      recording process and the resolution of the readout signal. The simulations show
      a drastic decrease with a widening air gap of the coupling efficiency by means of
      evanescent waves into the recording medium. In magneto-optical readout, loss of
      the signal may be attributed to the reduction of magneto-optical interaction, the
      rise of reflectance, and the variation of the relative phase between the two
      components of polarization. In the phase-change readout the reduced reflectivity
      contrast between crystalline and amorphous marks is the cause of signal
      reduction.

PMID- 18337899
TI  - Computation of effective groove depth in an optical disk with vector diffraction
      theory.
AB  - Results of vector diffraction simulations pertaining to the effective groove
      depth for various disks with different groove parameters, different coatings, and
      different incident polarizations are presented. The effective depth deviates from
      the physical depth if the track pitch approaches the wavelength of the light
      source. Moreover, the difference of the effective depth for the two polarization
      states is demonstrated. The effective depth is usually shallower than the
      physical depth, especially for deeper grooves. The ray-bending mechanism
      associated with the objective lens and the different response to s- and p
      polarized light on reflection from the disk surface impact the effective depth
      for objective lenses with different numerical apertures.

PMID- 18337900
TI  - Optical field study of near-field optical recording with a solid immersion lens.
AB  - The use of a solid immersion lens (SIL) is an important technique for increasing
      areal density in optical recording. Here an approximate method is presented for
      analyzing the optical fields in a SIL above a half-space and a SIL above a
      multilayer recording medium. Both propagating and evanescent components are
      included in the distribution of fields below the SIL. An approximate closed-form
      expression is given for the decay of the intensity away from the SIL surface
      above a half-space. In the case of a SIL above a recording medium the model
      describes the strong oscillations that are observed in the reflected Kerr
      rotation and ellipticity as the medium spacing is varied. These oscillations are
      attributed to standing waves in the propagating field component.

PMID- 18337901
TI  - Discussion on multidimensional fuzzy control.
AB  - Fuzzy-logic inference engines are in use in various disciplines such as control
      systems, medicine, and the like. The use of optical tools to implement such
      engines may improve the performance and the flexibility of inference procedures.
      The optical processor works in a two-dimensional environment, whereas the
      inference engine might have to handle more than two independent input channels.
      Here several approaches to generating the first, to our knowledge, N-dimensional
      optical fuzzy processor are addressed. The first approach uses space
      multiplexing, the second approach uses polarization multiplexing, and the third
      approach uses wavelength multiplexing to increase the dimension of the processor.

PMID- 18337902
TI  - Programmable color liquid-crystal television spatial light modulator:
      transmittance properties and application to speckle-correlation displacement
      measurement.
AB  - Drive electronics developed for a color liquid-crystal television (LCTV) display
      enable data to be written onto individual pixels. Display transmittance
      characteristics obtained with the new and the original TV drive electronics are
      compared. The enhanced performance obtained through this development has some
      potential for spatial light modulator applications in color, optical information
      processing based on the low-cost LCTV. As an example, we describe a novel, to our
      knowledge, speckle metrology technique used to display fringes and to output
      correlation peaks resulting from in-plane object displacement. This requires only
      a single LC display to encode, simultaneously in three pixel colors, speckle and
      fringe patterns for real-time measurements. Relative merits of this technique,
      including displacement range and temporal resolution, are discussed.

PMID- 18337903
TI  - Adjacency effects on water surfaces: primary scattering approximation and
      sensitivity study.
AB  - The making of atmospheric corrections is a critical task in the interpretation of
      ocean color imagery. In coastal areas, a fraction of the light reflected by the
      land reaches a sensor. Modeling the reduction of image contrast when the
      atmospheric turbidity increases, the so-called adjacency effect, requires large
      amounts of computing time. To model this effect we developed a simple approach
      based on the primary scattering approximation for both nadir and off-nadir views.
      A sensitivity study indicates that the decisive criterion for measurement
      accuracy for aerosols is their vertical distribution. As this distribution cannot
      generally be determined from space, it is not possible to include a suitable
      correction of the adjacency effects on satellite imagery. Conversely, we propose
      a simple correction for molecular scattering based on the isotropic
      approximation. We also address the problem of reduction of the coupling between
      the Fresnel reflection and the atmosphere for observations of coastal water. We
      study the influence of the adjacency effects on determination of the abundance of
      chlorophyll in water by combining use of the red and the infrared bands for
      aerosol remote sensing and the blue/green-ratio technique for retrieval of these
      data.

PMID- 18337904
TI  - Spectral diversity technique for heterodyne Doppler Lidar that uses hard target
      returns.
AB  - A two-mode CO(2) laser is used as transmitter in a 10-microm heterodyne Doppler
      lidar (HDL) to take advantage of a spectral diversity technique, i.e.,
      independent realizations obtained with different spectral components. The
      objective is to improve the properties (i.e., less variance) of power returns
      from a hard target. The statistical properties are presented first for a broad
      spectrum laser transmitter and then for a two-mode laser transmitter. The
      experimental results for a cooperative diffuse hard target show that the return
      signals for a frequency separation Deltaf = 15 MHz can be decorrelated, depending
      on the angle of incidence and the target roughness. The experimental results show
      that the spectral diversity technique improves the performance of the HDL.

PMID- 18337905
TI  - SALOMON: a new, light balloonborne UV-visible spectrometer for nighttime
      observations of stratospheric trace-gas species.
AB  - A new, light balloonborne UV-visible spectrometer, called SALOMON, is designed to
      perform nighttime measurements of stratospheric trace-gas species by using the
      Moon as a light source. The first flight, performed on 31 October 1998 at mid
      latitude with a float altitude of 26.7 km, allowed the performance of the
      pointing system to be checked and vertical profiles of ozone, NO(2), NO(3), and
      possibly OBrO to be obtained. First the instrument and then the performance of
      the pointing system and the detector are described. Finally the vertical profiles
      are compared with other profiles obtained at the same location five years before
      with the heavier balloonborne spectrometer AMON, which uses a star as the light
      source.

PMID- 18337906
TI  - Simulation of laser propagation in a turbulent atmosphere.
AB  - The split-step Fourier-transform algorithm for numerical simulation of wave
      propagation in a turbulent atmosphere is refined to correctly include the effects
      of large-scale phase fluctuations that are important for imaging problems and
      many beam-wave problems such as focused laser beams and beam spreading. The
      results of the improved algorithm are similar to the results of the traditional
      algorithm for the performance of coherent Doppler lidar and for plane-wave
      intensity statistics because the effects of large-scale turbulence are less
      important. The series solution for coherent Doppler lidar performance converges
      slowly to the results from simulation.

PMID- 18337907
TI  - Fabrication and characterization of diffractive optical elements in InP for
      monolithic integration with surface-emitting components.
AB  - We report on the fabrication and subsequent characterization of binary
      diffractive optical elements (DOE's) in InP for operation at 1.3 microm. Fresnel
      lenses of different focal lengths and a DOE that splits and focuses an incident
      beam into a 1 x 4 array of spots (optical fan-out) were fabricated. We realized
      the surface reliefs by patterning resist, using electron-beam lithography and
      etching with a chemically assisted ion beam, which produced well-defined patterns
      with smooth sidewalls and little if no surface roughness. The measured efficiency
      for the lenses was 36%. For the fan-out element the efficiency and the uniformity
      error were 26% and 30%, respectively. Spot sizes as small as 16 microm were
      measured.

PMID- 18337908
TI  - French transportable laser ranging station: scientific objectives, technical
      features, and performance.
AB  - The French Transportable Laser Ranging Station (FTLRS) is a highly mobile
      satellite laser ranging (SLR) system unit that weighs 300 kg and is housed in
      eight containers. This telemetry laser station is dedicated to the tracking of
      geodetic satellites equipped with retroreflectors. There are fascinating uses in
      the geosciences for such a system: in tectonics, oceanography, terrestrial
      reference frames, and precise positioning. The idea is to use a very small 13-cm
      diameter telescope installed on a motorized mount and derived from a geodetic
      motorized theodolite of high precision. The laser is also compact, and the use of
      an avalanche photodiode makes detection possible at a single photoelectron level.
      On-site installation of this new SLR system is fast, and the system's routine
      operation is quite automated. It started its operational phase in late 1996. At
      present, it can track satellites at altitudes of as much as 3000 km and is
      designed to range to the Laser Geodynamic Earth Orientation Satellite (LAGEOS) at
      6000 km in a further step. The standard error of individual measurements during
      the first observation campaign in Corsica is estimated to be of the order of 2-3
      cm. Since then, significant improvements have been implemented. A technical
      description of the FTLRS is given, and the main results of the Corsica campaign
      are summarized.

PMID- 18337909
TI  - Optical remote sensing inside an inhomogeneous axisymmetric medium: the
      absorption field measurement.
AB  - It is shown that the absorption field inside an inhomogeneous, rotationally
      symmetric medium with a spatially variable refractive index can be reconstructed
      by means of a tomographic technique. The classic Abel transform is extended to
      non-Euclidean optical media. The optical behavior of such a medium is described
      and, provided that the product of the refractive index with the radial distance
      is a monotonic function, an exact inverse formula is found. Both a numerical and
      an analytical test on a phantom function is carried out to prove the exactness of
      this formula. In contrast, when the assumption of a monotonic function is not
      true, it is shown that the reconstruction problem becomes subdeterminate because
      of the presence of annular regions, known as blind areas, inside of which no
      curved path reaches an extremum. The spatial localization and the size of these
      regions are related to the extrema of the index of refraction times the radial
      distance.

PMID- 18337910
TI  - Radiometric calibration of the vacuum-ultraviolet spectrograph SUMER on the SOHO
      spacecraft with the B detector.
AB  - The Solar Ultraviolet Measurement of Emitted Radiation (SUMER) vacuum-ultraviolet
      spectrograph was calibrated in the laboratory before the integration of the
      instrument on the Solar and Heliospheric Observatory (SOHO) spacecraft in 1995.
      During the scientific operation of the SOHO it has been possible to track the
      radiometric calibration of the SUMER spectrograph since March 1996 by a strategy
      that employs various methods to update the calibration status and improve the
      coverage of the spectral calibration curve. The results for the A Detector were
      published previously [Appl. Opt. 36, 6416 (1997)]. During three years of
      operation in space, the B detector was used for two and one-half years. We
      describe the characteristics of the B detector and present results of the
      tracking and refinement of the spectral calibration curves with it. Observations
      of the spectra of the stars alpha and rho Leonis permit an extrapolation of the
      calibration curves in the range from 125 to 149.0 nm. Using a solar coronal
      spectrum observed above the solar disk, we can extrapolate the calibration curves
      by measuring emission line pairs with well-known intensity ratios. The
      sensitivity ratio of the two photocathode areas can be obtained by registration
      of many emission lines in the entire spectral range on both KBr-coated and bare
      parts of the detector's active surface. The results are found to be consistent
      with the published calibration performed in the laboratory in the wavelength
      range from 53 to 124 nm. We can extrapolate the calibration outside this range to
      147 nm with a relative uncertainty of ?30% (1varsigma) for wavelengths longer
      than 125 nm and to 46.5 nm with 50% uncertainty for the short-wavelength range
      below 53 nm.

PMID- 18337911
TI  - Vertical antiresonant reflecting optical waveguide coupler for three-dimensional
      optical interconnects: optimum design for large tolerance, high coupling
      efficiency, and short coupling length.
AB  - A compact antiresonant-reflecting-optical-waveguide-(ARROW-) type vertical
      coupler for three-dimensional optical interconnects was demonstrated. The coupler
      consists of stacked ARROW's channeled by the stripe lateral confinement
      structure, and each waveguide is completely separated by a thin metal film in the
      separation region. In the coupling region the intermediate cladding of a previous
      coupler was made of the same material as that of the first cladding or the core.
      However, we had to overcome the problem that both the high coupling efficiency
      and the large fabrication tolerance cannot be achieved simultaneously. Thus we
      incorporated an intermediate cladding made of a material different from that of
      the core and the first cladding. The refractive index and the thickness of the
      intermediate cladding were optimally designed to achieve large fabrication
      tolerance and a short coupling length with a high coupling efficiency. The
      coupling length was reduced from 4.1 to 0.8 mm, and a high coupling efficiency of
      96% was experimentally demonstrated.

PMID- 18337912
TI  - Linearly polarized 100-W output from a diode-pumped Nd:YAlO laser.
AB  - We demonstrate a compact cw diode-pumped Nd:YAlO laser that can produce 100 W of
      power at 1079 nm and 18.3 W at 1341 nm. Lasing and nonlasing thermal lensing data
      are presented.

PMID- 18337913
TI  - Planar waveguides formed by Ag+-Na+ ion exchange in nonlinear optical glasses:
      diffusion and optical properties.
AB  - All-optical communication systems are the subject of intense research related to
      the integration of nonlinear optical materials. In sodiocalcic borophosphate
      glasses that contain niobium oxide and exhibit high nonlinear optical indices,
      planar waveguides have been formed by a Ag(+)-Na(+) ion-exchange technique. WKB
      analysis has been used to characterize the diffusion profiles of silver ions
      exchanged in glass substrate samples chemically by an electron microprobe
      technique and optically by an M-line technique. These methods permit the Ag(+)
      penetration depth and diffusion profile shape and index profiles to be
      determined. The results are analyzed and discussed in relation to Ca(2+)
      concentration and exchange conditions in glasses. The Ag(+) diffusion in these
      glasses can be almost entirely controlled for index-profile engineering.

PMID- 18337914
TI  - Nonintrusive optical measurements of aircraft engine exhaust emissions and
      comparison with standard intrusive techniques.
AB  - Nonintrusive systems for the measurement on test rigs of aeroengine exhaust
      emissions required for engine certification (CO, NO(x), total unburned
      hydrocarbon, and smoke), together with CO(2) and temperature have been developed.
      These results have been compared with current certified intrusive measurements on
      an engine test. A spectroscopic database and data-analysis software has been
      developed to enable Fourier-transform Infrared measurement of concentrations of
      molecular species. CO(2), CO, and NO data showed agreement with intrusive
      techniques of approximately ?30%. A narrow-band spectroscopic device was used to
      measure CO(2) (with deviations of less than ?10% from the intrusive measurement),
      whereas laser-induced incandescence was used to measure particles. Future
      improvements to allow for the commercial use of the nonintrusive systems have
      been identified and the methods are applicable to any measurement of combustion
      emissions.

PMID- 18337915
TI  - Remote-sensing reflectance determinations in the coastal ocean environment:
      impact of instrumental characteristics and environmental variability.
AB  - Three independent ocean color sampling methodologies are compared to assess the
      potential impact of instrumental characteristics and environmental variability on
      shipboard remote-sensing reflectance observations from the Santa Barbara Channel,
      California. Results indicate that under typical field conditions, simultaneous
      determinations of incident irradiance can vary by 9-18%, upwelling radiance just
      above the sea surface by 8-18%, and remote-sensing reflectance by 12-24%.
      Variations in radiometric determinations can be attributed to a variety of
      environmental factors such as Sun angle, cloud cover, wind speed, and viewing
      geometry; however, wind speed is isolated as the major source of uncertainty. The
      above-water approach to estimating water-leaving radiance and remote-sensing
      reflectance is highly influenced by environmental factors. A model of the role of
      wind on the reflected sky radiance measured by an above-water sensor illustrates
      that, for clear-sky conditions and wind speeds greater than 5 m/s, determinations
      of water-leaving radiance at 490 nm are undercorrected by as much as 60%. A data
      merging procedure is presented to provide sky radiance correction parameters for
      above-water remote-sensing reflectance estimates. The merging results are
      consistent with statistical and model findings and highlight the importance of
      multiple field measurements in developing quality coastal oceanographic data sets
      for satellite ocean color algorithm development and validation.

PMID- 18337916
TI  - Scattering of electromagnetic radiation by multilayered spheroidal particles:
      recursive procedure.
AB  - A formalism is developed for the calculation of the electromagnetic field
      scattered by a multilayered spheroidal particle. The suggested formalism utilizes
      the recursive approach with respect to passing from one layer to the next; thus
      it does not require an increase in the size of the equation matrices involved as
      the number of layers increases. The equations operate with matrices of the same
      size as for a homogeneous spheroid. The special cases of extremely prolate and
      weakly prolate spheroids are considered in more detail. It is shown that in such
      cases one can avoid the matrix calculations by instead using the iterative scalar
      calculations.

PMID- 18337917
TI  - Diffraction gratings of photosensitive ZrO2 gel films fabricated with the two
      ultraviolet-beam interference method.
AB  - Photosensitive ZrO(2) gel films were patterned with a two-beam interference
      method by use of a 325-nm-wavelength He-Cd laser for the first time to our
      knowledge. The ZrO(2) gel films were prepared from Zr(O-n-C(4)H(9))(4) chemically
      modified with benzoylacetone. We fabricated uniform gratings with a 0.5-microm
      period on Si or SiO(2) substrates by etching the gel films in ethyl alcohol after
      UV irradiation. A maximum diffraction efficiency of 28% was attained with the
      grating fabricated on Si substrate under a Littrow mounting condition by use of a
      633-nm-wavelength He-Ne laser. Blazed gratings could also be fabricated.

PMID- 18337918
TI  - Plastic bending of sapphire fibers for infrared sensing and power-delivery
      applications.
AB  - Sapphire fibers with diameters of 325-850 microm were plastically bent by CO(2)
      laser beams with typical bending radii as small as 2.8 mm. The additional optical
      loss caused by a single bend was less than 0.1 dB (at 900 nm), the damage
      threshold of the bent fibers was higher than 150 MW/cm(2) for Nd:YAG laser
      pulses, and the high mechanical strength of the bending area was also proved.
      Several successful applications of bent sapphire fibers have shown that
      plastically bent sapphire fibers are promising for use in IR sensing and power
      delivery applications.

PMID- 18337919
TI  - Improved regularized phase-tracking technique for the processing of squared
      grating deflectograms.
AB  - We propose a robust procedure based on the regularized phase-tracking (RPT)
      technique to demodulate squared-grating deflectograms. The use of squared
      gratings, already reported, lets us multiplex the information of the deflections
      in two orthogonal directions in a single image, thus avoiding the necessity of
      rotating the gratings. The good noise-rejection characteristics of the RPT
      technique are improved by use of a quasi-Newton optimization algorithm and a
      quality-map-based algorithm for the crystal-growing process.

PMID- 18337920
TI  - Effect of scattering on nonlinear optical scanning microscopy imaging of highly
      scattering media.
AB  - The intensity of two-photon excited fluorescence (TPF) generated by ultrashort
      laser pulses was measured as a function of the depth of a focal point inside
      highly scattering media. The purpose was to investigate the spatial location of
      TPF in a scattering medium. Owing to the scattering, the intensity of the
      incident beam as well as the generated TPF signal was attenuated exponentially as
      the focal point was scanned into the medium. As the scattering strength of the
      medium was increased, the TPF was not confined to the focal region and had a
      wider distribution. These observations show that the scattering will result in
      the degradation of the ability of optical depth sectioning of nonlinear optical
      scanning microscopy.

PMID- 18337921
TI  - Liquid-crystal-display projector-based modulation transfer function measurements
      of charge-coupled-device video camera systems.
AB  - We demonstrate the ability to measure the system modulation transfer function
      (MTF) of both color and monochrome charge-coupled-device (CCD) video camera
      systems with a liquid-crystal-display (LCD) projector. Test matrices programmed
      to the LCD projector were chosen primarily to have a flat power spectral density
      (PSD) when averaged along one dimension. We explored several matrices and present
      results for a matrix produced with a random-number generator, a matrix of
      sequency-ordered Walsh functions, a pseudorandom Hadamard matrix, and a
      pseudorandom uniformly redundant array. All results are in agreement with
      expected filtering. The Walsh matrix and the Hadamard matrix show excellent
      agreement with the matrix from the random-number generator. We show that shift
      variant effects between the LCD array and the CCD array can be kept small. This
      projector test method offers convenient measurement of the MTF of a low-cost
      video system. Such characterization is useful for an increasing number of machine
      vision applications and metrology applications.

PMID- 18337922
TI  - Precise interferometric length and phase-change measurement of gauge blocks based
      on reproducible wringing.
AB  - A modern fringe-pattern-analyzing interferometer with a resolution of 1 x 10(-9)
      and without exclusion of systematic uncertainties owing to optic effects of less
      than 1 nm was used to test a new method of interferometric length measurement
      based on a combination of the reproducible wringing and slave-block techniques.
      Measurements without excessive wringing film error are demonstrated for blocks
      with nominal lengths of 2-6 mm and with high surface flatness. The uncertainty
      achieved for these blocks is less than 1 nm. Deformations of steel gauge blocks
      and reference platens, caused by wringing forces, are investigated, and the
      necessary conditions for reproducible wringing are outlined. A subnanometer
      uncertainty level in phase-change-correction measurements has been achieved for
      gauge blocks as long as 100 mm. Limitations on the accuracy standard method of
      interferometric length measurements and shortcomings of the present definition of
      the length of the material artifact are emphasized.

PMID- 18337923
TI  - Optical technique for the automatic detection and measurement of surface defects
      on thin metallic wires.
AB  - In industrial applications of thin metallic wires it is important to characterize
      the surface defects of the wires. We present an optical technique for the
      automatic detection of surface defects on thin metallic wires (diameters, 50-2000
      microm) that can be used in on-line systems for surface quality control. This
      technique is based on the intensity variations on the scattered cone generated
      when the wire is illuminated with a beam at oblique incidence. Our results are
      compared with those obtained by atomic-force microscopy and scanning-electron
      microscopy.

PMID- 18337924
TI  - Surface temperature-field imaging with laser-induced thermographic
      phosphorescence.
AB  - A technique to remotely image temperature distributions of heated metallic
      surfaces is extended to higher temperatures. It uses a Dy(+3):YAG thermographic
      phosphor (TP) bonded to the surface and excited by radiation at 355 nm. Digital
      images of the emission from two excited states were recorded and divided by each
      other to correct by normalization for illumination and coating nonuniformities.
      Results show that the TP can survive heating and cooling cycles to 1400 K and
      that emitting states achieve thermodynamic equilibrium before radiating.
      Temperatures in the range of 300-1300 K were determined by normalization of pairs
      of emission images with a single calibration constant. Uncertainties of +/-7-13%
      at a spatial resolution of 20 microm and +/-0.7-4% at a resolution of 500 microm
      were achieved.

PMID- 18337925
TI  - Application of fiber-optic bragg grating sensors in monitoring environmental
      loads of overhead power transmission lines.
AB  - We demonstrate the capability of using fiber-optic sensors for measurements on
      environmental loads on a high-power, overhead transmission line. A trial system
      with three Bragg gratings, including a temperature reference, was installed on a
      160-m span of a 60-kV line. An interrogation system with a tunable distributed
      Bragg reflector laser source was used. Several measurements of the induced loads
      on a conductor were recorded in various wind conditions. In particular, aeolian
      vibrations were frequently observed, and several measurements of this phenomenon
      were made. The results correlate well with simple theoretical predictions and
      visual observations.

PMID- 18337926
TI  - Wave-front reconstruction with a shack-hartmann sensor with an iterative spline
      fitting method.
AB  - One limitation of the conventional Shack-Hartmann sensor is that the spots of
      each microlens have to remain in their respective subapertures. We present an
      algorithm that assigns the spots to their reference points unequivocally even if
      they are situated far outside their subaperture. For this assignment a spline
      function is extrapolated in successive steps of the iterative algorithm. The
      proposed method works in a single-shot technique and does not need any aid from
      mechanical devices. The reconstruction of a simulated steep aspherical wave front
      (approximately 100 lambda/mm slope) is described as well as experimental results
      of the measurement of a spherical wave front with a huge peak-to-valley value
      (approximately 400 lambda). The performance of the method is compared with the
      unwrapping method, which has been published before.

PMID- 18337927
TI  - Constant-bandwidth scanning of the Czerny-Turner monochromator.
AB  - For the convenience of monochromator users, the constant-bandwidth operation of a
      Czerny-Turner monochromator is reviewed and clarified for continuously variable
      and for discretely variable slit widths. A procedure for selecting the discrete
      slit widths that are necessary for nearly constant-bandwidth scanning is
      presented.

PMID- 18337928
TI  - Optical configuration for TV holography measurement of in-plane and out-of-plane
      deformations.
AB  - A novel TV holography method is proposed for parallel evaluation of in-plane and
      out-of-plane deformation fields. The method permits a trade-off between in-plane
      and out-of-plane measuring sensitivity. A four-exposure, four-frame phase
      shifting technique is used in the experiments; the experimental results for an
      aluminum specimen subjected to both rotation in its own plane and a bending
      couple load at the center are presented.

PMID- 18337929
TI  - Scanning laser differential-heterodyne interferometer for flying-height
      measurement.
AB  - With conventional optical interferometry flying-height testing, a stationary
      measurement beam and a two-axis moving stage are used to measure slider-disk
      spacing at different points on the slider. Pitch angle or roll angle is
      calculated on the basis of the measurement results. We report on a scanning
      differential-heterodyne interferometer, which measures the continuous flying
      height variation along the edge of a slider with two continuously scanning laser
      beams. Pitch angle or roll angle can be obtained directly from the scanning
      measurement. The system can also measure points individually to obtain the
      absolute flying height at different locations on the slider. Experiments were
      performed to demonstrate the concept of scanning measurement. The flying-height
      variation along the slider edge was measured by continuous scan and by point-to
      point moving. The measurement results from continuous scan coincided with those
      of conventional methods.

PMID- 18337930
TI  - Phase-shifting interferometry with uncalibrated phase shifts.
AB  - A computationally efficient algorithm for phase-shifting interferometry with
      imprecise phase shifts is developed. It permits the use of an uncalibrated phase
      shifter and is also insensitive to spatial intensity variations. The measurement
      has both spatial and temporal aspects. Comparisons are made between pixels within
      the same interferogram, and these comparisons are extended across a set of
      interferograms by a maximum-minimum procedure. A test experiment is performed and
      confirms the theoretical results. An additional advantage of the algorithm is
      that an error measure can be developed. This error measure is used to implement
      an error correction scheme.

PMID- 18337931
TI  - Aberrations introduced by a lens made from a birefringent material.
AB  - We incorporate an algorithm for ray tracing in birefringent media into a full ray
      tracing package based on the Mathematica software application. To validate the
      package, we compare the calculated and observed wave-front aberration introduced
      by an optical system that comprises lenses fabricated from birefringent material.
      Using the package, we calculate the influence of the lens shape factor on the
      aberrations associated with the e-ray polarization and show that it differs
      significantly from that of the o-ray polarization.

PMID- 18337932
TI  - Ion-beam machining of millimeter scale optics.
AB  - An ion-beam microcontouring process is developed and implemented for figuring
      millimeter scale optics. Ion figuring is a noncontact machining technique in
      which a beam of high-energy ions is directed toward a target substrate to remove
      material in a predetermined and controlled fashion. Owing to this noncontact mode
      of material removal, problems associated with tool wear and edge effects, which
      are common in conventional machining processes, are avoided. Ion-beam figuring is
      presented as an alternative for the final figuring of small (<1-mm) optical
      components. The depth of the material removed by an ion beam is a convolution
      between the ion-beam shape and an ion-beam dwell function, defined over a two
      dimensional area of interest. Therefore determination of the beam dwell function
      from a desired material removal map and a known steady beam shape is a
      deconvolution process. A wavelet-based algorithm has been developed to model the
      deconvolution process in which the desired removal contours and ion-beam shapes
      are synthesized numerically as wavelet expansions. We then mathematically
      combined these expansions to compute the dwell function or the tool path for
      controlling the figuring process. Various models have been developed to test the
      stability of the algorithm and to understand the critical parameters of the
      figuring process. The figuring system primarily consists of a duo-plasmatron ion
      source that ionizes argon to generate a focused (approximately 200-microm FWHM)
      ion beam. This beam is rastered over the removal surface with a perpendicular set
      of electrostatic plates controlled by a computer guidance system. Experimental
      confirmation of ion figuring is demonstrated by machining a one-dimensional
      sinusoidal depth profile in a prepolished silicon substrate. This profile was
      figured to within a rms error of 25 nm in one iteration.

PMID- 18337933
TI  - Comparative analysis of absorbance calculations for integrated optical waveguide
      configurations by use of the ray optics model and the electromagnetic wave
      theory.
AB  - Focusing on the use of planar waveguides as platforms for highly sensitive
      attenuated total reflection spectroscopy of organic thin films, we extend the ray
      optics model to provide absorbance expressions for the case of dichroic layers
      immobilized on the waveguide surface. Straightforward expressions are derived for
      the limiting case of weakly absorbing, anisotropically oriented molecules in the
      waveguide-cladding region. The second major focus is on the accuracy of the ray
      optics model. This model assumes that the introduction of absorbing species,
      either in the bulk cladding or as an adlayer on the waveguide surface, only
      causes a small perturbation to the original waveguide-mode profile. We
      investigate the accuracy of this assumption and the conditions under which it is
      valid. A comparison to an exact calculation by use of the electromagnetic wave
      theory is implemented, and the discrepancy of the ray optics model is determined
      for various waveguide configurations. We find that in typical situations in which
      waveguide-absorbance measurements are used to study organic thin films (k(l)/n(l)
      <or= (-1), h/lambda approximately (-2)) the discrepancy between the ray optics
      and the exact calculations is only a few percent (2-3%).

PMID- 18337934
TI  - Absorption and scattering of light by pigment particles in solar-absorbing
      paints.
AB  - The optical properties of black-pigmented solar absorbing paint were analyzed
      phenomenologically by use of the Kubelka-Munk theory, including correction for
      reflection on front and rear surfaces. The effective absorption and scattering
      coefficients and the efficiency curves for absorption and scattering were
      calculated for coatings with different pigment-to-volume concentration ratios.
      The dependence of absorption and scattering efficiency on the pigment-to-volume
      concentration ratio was analyzed by reference to theoretical data in the
      literature. It was concluded that, during drying and curing of coatings,
      spherical primary pigment particles most likely collect in elongated groups
      oriented perpendicularly to the coating surface. Formation of such groups helps
      in understanding the independent measurements of solar absorptance.

PMID- 18337935
TI  - Phase-modulated mueller ellipsometry characterization of scattering by latex
      sphere suspensions.
AB  - Phase-modulated Mueller ellipsometry (PMME) is used to probe scattering by
      suspensions of polystyrene latex spheres, with particle diameters ranging from
      400 nm to 3 microm. PMME allows simultaneous measurement of the 16 coefficients
      of the Mueller matrix. Furthermore PMME measurements can easily be carried out
      owing to a calibration procedure implemented in a scattering configuration. The
      measurements performed on low concentrations show good agreement with Mie theory.
      Moreover size distribution could be obtained with a least-squares method based on
      a genetic fit algorithm. Experimental evidence of multiple scattering on PMME
      measurements is also presented.

PMID- 18337936
TI  - Image plates for registration of far-ultraviolet spectra.
AB  - We have tested an autoradiographic photostimulable phosphor image storage plate
      as a medium for recording spectra in the wavelength region from 50 to 550 A and
      have compared the results with spectra obtained with conventional photographic
      emulsions. The image plate shows sensitivity comparable with the photographic
      plates but has a linear intensity response over a much wider dynamic range.
      Resolution of current image-plate systems is limited by the scanner that reads
      the stored image from the phosphor plate, but this limitation is not fundamental.
      These initial results suggest that optimized image plates with an improved
      scanner would provide a favorable alternative to photographic plates in this
      spectral region.

PMID- 18337937
TI  - Vacuum deposition of chiral sculptured thin films with high optical activity.
AB  - We present the technique of bideposition to realize thin-film helicoidal
      bianisotropic mediums (TFHBM's) that exhibit high optical activity. We show, by
      experiment as well as by simulation, that the optical rotation produced by these
      chiral sculptured thin films is roughly proportional to the square of the local
      linear birefringence. Experimental measurements on bideposited TFHBM's of
      titanium oxide yield a typical value of 5 degrees /mum for the effective specific
      rotation in the short-wavelength regime; the corresponding value determined for
      the standard unideposited TFHBM's is 1 degrees /mum. Both types of TFHBM's are
      highly optically active in comparison with quartz, fluorite films, and
      cholesteric liquid crystals. Bideposited TFHBM's will lend themselves to many
      different types of optical devices.

PMID- 18337938
TI  - Absorptance behavior of optical coatings for high-average-power laser
      applications.
AB  - A modified photothermal deformation technique is used to measure the absorptance
      behaviors of optical multilayered dielectric coatings for a high-power laser
      system. The surface thermal-lensing modification uses an enlarged probe beam to
      facilitate alignment of the laser beam and data acquisition. The coatings, both
      reflective and transmissive types, are made by a physical vapor-deposition
      process. Coating absorptances are observed to depend on the laser's exposure time
      and power density. Time-dependent absorptance defect models are proposed. Also,
      micrometer-sized sites of high absorptance and an area with physical damage can
      be found during the spatial scans. It is proposed that absorptance values
      reported for coatings in high-repetition-rate or cw-laser systems include time-
      and power-dependent behaviors in addition to other relevant irradiation
      parameters.

PMID- 18337939
TI  - Theoretical and experimental studies of ultrasound-modulated optical tomography
      in biological tissue.
AB  - Ultrasound-modulated optical tomography in biological tissue was studied both
      theoretically and experimentally. An ultrasonic beam was focused into biological
      tissue samples to modulate the laser light passing through the ultrasonic beam
      inside the tissue. The ultrasound-modulated laser light reflects the local
      optical and mechanical properties in the ultrasonic beam and permits tomographic
      imaging of biological tissues by scanning. Parallel detection of the speckle
      field formed by the transmitted laser light was implemented with the source
      synchronous-illumination lock-in technique to improve the signal-to-noise ratio.
      Two-dimensional images of biological tissues were successfully obtained
      experimentally with a laser beam at either normal or oblique incidence, which
      showed that ultrasound-modulated optical tomography depends on diffuse light
      rather than on ballistic light. Monte Carlo simulations showed that the
      modulation depth decreased much more slowly than the diffuse transmittance, which
      indicated the possibility that even thicker biological tissues can be imaged with
      this technique.

PMID- 18337940
TI  - Optics in computing: introduction to the feature issue.
AB  - This issue of Applied Optics features 21 papers that describe the implementation
      of optics in computer systems and applications. This feature is the eighth in a
      series on the application of optics in the field of computing.

PMID- 18337941
TI  - Architectural approach to the role of optics in monoprocessor and multiprocessor
      machines.
AB  - The relevance of introducing optical interconnects (OI's) in monoprocessors and
      multiprocessors is studied from an architectural point of view. We show that
      perhaps the major explanation for why optical technologies have nearly been
      unable to penetrate into computers is that OI's generally do not shorten the
      memory-access time, which is the most critical issue for today's stored-program
      machines. In monoprocessors the memory-access time is dominated by the electronic
      latency of the memory itself. Thus implementing OI's inside the memory hierarchy
      without changing the memory architecture cannot dramatically improve the global
      performance. In strongly coupled multiprocessors the node-bypass latency
      dominates. Therefore the higher the connectivity (possibly with optics), the
      shorter the path to another node, but the more expensive the network and the more
      complex the structure of electronic nodes. This relation leaves the choice of the
      best network open in terms of simplicity and latency reduction. The bottlenecks
      resulting from and the benefits of implementing OI's are discussed with respect
      to symmetric multiprocessors, rings, and distributed shared-memory
      supercomputers.

PMID- 18337942
TI  - Interconnection of a two-dimensional array of vertical-cavity surface-emitting
      lasers to a receiver array by means of a fiber image guide.
AB  - The implementation of a 10-channel parallel optical interconnect consisting of a
      two-dimensional array of vertical-cavity surface-emitting lasers, a 1.35-m fiber
      image guide, and a metal-semiconductor-metal receiver array is described.
      Transmission rates of 250 Mbits/s per channel are demonstrated with an optical
      cross talk of less than -27 dB and a loss of -3 dB. Coupling issues associated
      with image guides are analyzed and discussed.

PMID- 18337943
TI  - Broadband parallel-fiber optical link for short-distance interconnection with
      multimode fibers.
AB  - In a multimode step-index fiber the propagation angle of a beam is conserved over
      short distances even if the fiber is bent slightly. This behavior can be
      exploited for a multiplexed signal transmission by the assignment of different
      channels to different propagation angles [angle-division multiplexing (ADM)].
      Thus parallel transmission can be achieved. Because each channel occupies only a
      subrange of the fiber's numerical aperture, modal dispersion is reduced compared
      with single-channel transmission through the same fiber. The transmission
      properties of an ADM-based transmission line are analyzed for short propagation
      distances. Passive all-optical setups for multiplexing and demultiplexing
      operations are proposed. Cross-talk measurements are shown for a transmission
      with a length of 8 m and 13 multiplexed channels.

PMID- 18337944
TI  - Demonstration of a multichannel optical interconnection by use of imaging fiber
      bundles butt coupled to optoelectronic circuits.
AB  - Through five experiments, we demonstrate and characterize the basic functionality
      of imaging fiber bundles for optoelectronic chip-level interconnections. We
      demonstrate the transmission of spot arrays with spot sizes and a spot pitch
      roughly equal to 2 and 4 times the core pitch, respectively. We show that
      optoelectronic integrated circuits, including sources and detectors, can be butt
      coupled directly to fiber bundles without any additional optical elements. We
      demonstrate a 16-channel interconnect with -23 dB of cross talk, and we
      characterize the most significant optical loss mechanism. Finally, we show how
      imaging fiber bundles can be used to implement more complex interconnection
      structures by an example of a hybrid-bonded structure that implements a low-cost,
      high-connectivity solution for more advanced system architectures.

PMID- 18337945
TI  - Experimental and numerical analyses of misalignment tolerances in free-space
      optical interconnects.
AB  - A comparison of numerical analyses with experimental measurements suggests that
      both the ray-tracing and the Gaussian beam-propagation models overestimate the
      misalignment tolerances for on-axis beams and fail to predict the large
      longitudinal focal shift that occurs for off-axis beams propagating in free-space
      optical interconnects.

PMID- 18337946
TI  - Low-order adaptive optics for free-space optoelectronic interconnects.
AB  - The concept of adaptive optics for improving the cost-performance of free-space
      optoelectronic interconnects is discussed. Adaptive optics as a design option for
      optical interconnect systems is presented and discussed. A practical demonstrator
      that performs low-order correction was built and tested. Slowly varying
      misalignments, including thermal effects, were compensated for in a 622-Mbit/s
      free-space optical data link.

PMID- 18337947
TI  - Field-programmable logic devices with optical input-output.
AB  - A field-programmable logic device (FPLD) with optical I/O is described. FPLD's
      with optical I/O can have their functionality specified in the field by means of
      downloading a control-bit stream and can be used in a wide range of applications,
      such as optical signal processing, optical image processing, and optical
      interconnects. Our device implements six state-of-the-art dynamically
      programmable logic arrays (PLA's) on a 2 mm x 2 mm die. The devices were
      fabricated through the Lucent Technologies-Advanced Research Projects Agency
      Consortium for Optical and Optoelectronic Technologies in Computing
      (Lucent/ARPA/COOP) workshop by use of 0.5-microm complementary metal-oxide
      semiconductor-self-electro-optic device technology and were delivered in 1998.
      All devices are fully functional: The electronic data paths have been verified at
      200 MHz, and optical tests are pending. The device has been programmed to
      implement a two-stage optical switching network with six 4 x 4 crossbar switches,
      which can realize more than 190 x 10(6) unique programmable input-output
      permutations. The same device scaled to a 2 cm x 2 cm substrate could support as
      many as 4000 optical I/O and 1 Tbit/s of optical I/O bandwidth and offer fully
      programmable digital functionality with approximately 110,000 programmable logic
      gates. The proposed optoelectronic FPLD is also ideally suited to realizing
      dense, statically reconfigurable crossbar switches. We describe an attractive
      application area for such devices: a rearrangeable three-stage optical switch for
      a wide-area-network backbone, switching 1000 traffic streams at the OC-48 data
      rate and supporting several terabits of traffic.

PMID- 18337948
TI  - Design, implementation, and characterization of a kinematically aligned, cascaded
      spot- array generator for a modulator-based free-space optical interconnect.
AB  - The design and the implementation of a modular spot-array generator for a
      modulator-based free-space optical interconnect is presented. Two cascaded
      diffractive optical elements produce 4 x 8 clusters on a 1600 microm x 800 microm
      pitch, where each cluster is a 4 x 4 array of (1/e(2)) 13.1-microm-radius spots
      on a 90-microm pitch. The spot-array generator is kinematically aligned to the
      interconnect system such that no realignment is necessary between removal and
      reinsertion. Characterization results are presented.

PMID- 18337949
TI  - Free-space optical cross-connect switch by use of electroholography.
AB  - An electrically controlled holographic switch is proposed as a building block for
      a free-space optical interconnection network. The switch is based on the voltage
      controlled photorefractive effect in KLTN crystals at the paraelectric phase. It
      is built of electrically controlled Bragg gratings stored in the volume of the
      crystal. A compact switch that connects four high-speed fiber-optic communication
      channels with high efficiency is demonstrated experimentally. The switch
      performance is investigated and optimized. This switch is extremely attractive
      for cascaded switching arrays such as those found in multistage interconnect
      networks.

PMID- 18337950
TI  - Compact planar-integrated optical correlator for spatially incoherent signals.
AB  - A new, to our knowledge, approach for the planar integration of optical
      correlators is demonstrated. A VanderLugt-type architecture was used to allow the
      processing of the spatially incoherent signals of active optoelectronic smart
      pixel-device arrays. In a folded optical system all passive components were
      implemented as a single multiple-phase-level element. The relations among the
      spatial resolution, the light efficiency, and the system design parameters are
      derived. High signal quality and low noise levels were achieved experimentally.

PMID- 18337951
TI  - Optical correlation by use of partial phase-only modulation with VGA liquid
      crystal displays.
AB  - The development of liquid-crystal panels for use in commercial equipment has been
      aimed at improving the pixel resolution and the display efficiency. These
      improvements have led to a reduction in the thickness of such devices, among
      other outcomes, that involves a loss in phase modulation. We propose a
      modification of the classical phase-only filter to permit displays in VGA liquid
      crystal panels with a constant amplitude modulation and less than a 2pi phase
      modulation. The method was tested experimentally in an optical setup.

PMID- 18337952
TI  - Improvement of the generalization capability for a pattern-recognition neural
      network that uses a Gaussian-synapse neuron model.
AB  - A method for improving the generalization capability for optical pattern
      recognition by use of a Gaussian-synapse neuron model is discussed. By the
      dispersive effect of the Gaussian function the input images are blurred and then
      fed into a multilayer neural network for learning and recognition. The
      effectiveness of this method is demonstrated in two-dimensional shift- and scale
      invariant optical pattern recognition.

PMID- 18337953
TI  - Nonlinear rotation-invariant pattern recognition by use of the optical
      morphological correlation.
AB  - We introduce a modification of the nonlinear morphological correlation for
      optical rotation-invariant pattern recognition. The high selectivity of the
      morphological correlation is conserved compared with standard linear correlation.
      The operation performs the common morphological correlation by extraction of the
      information by means of a circular-harmonic component of a reference. In spite of
      some loss of information good discrimination is obtained, especially for
      detecting images with a high degree of resemblance. Computer simulations are
      presented, as well as optical experiments implemented with a joint transform
      correlator.

PMID- 18337954
TI  - Reconfigurable optical neuron based on photoelectret materials.
AB  - An all-optical reconfigurable neuron based on a photoelectret-electro-optic
      medium with a sandwich-type structure is presented. Both the inputs and the
      output of the neuron and the reconfiguration of the weights of the inputs are
      optical. The structure presented is very versatile and exhibits low energy
      consumption, as the numerical estimates indicate. The number of inputs can be
      varied (to an upper limit that is determined by the diffraction effect) without
      changing the structure of the optical neuron; the same is true for the neurons'
      weights.

PMID- 18337955
TI  - Optoelectronic neural-network scheduler for packet switches.
AB  - A novel, to our knowledge, type of packet scheduler that could significantly
      outperform current state-of-the-art schedulers is presented. The operation and
      the design of such a scheduler are discussed, and a fully operational
      experimental implementation is described. The scheduler uses a neural network in
      a winner-take-all strategy to optimize decisions on the throughput of both a
      crossbar and a banyan switching fabric. The problems of high interconnection
      density are solved by use of a free-space optical interconnect that exploits
      diffractive optical techniques to generate the required interconnection patterns
      and weights.

PMID- 18337956
TI  - Image distance transforms that use optical correlation.
AB  - The image distance transform is a time-consuming global operation. We use optical
      correlation for the fast computation of binary image distance transforms. A joint
      transform correlator is proposed to implement the algorithm that accommodates the
      morphological threshold-decomposition concept. The proposed optical processor is
      programmable for computing Euclidean, city-block, and chessboard distance
      transforms in real time. Skeletonization by use of the distance transform and the
      rotation invariance of the Euclidean distance transform are demonstrated.

PMID- 18337957
TI  - Optically computing the hit-miss transform for an automated cervical smear
      screening system.
AB  - The hit-miss transform serves as a region-of-interest locator for cells from
      cervical smear images that show abnormal changes, which are indicative of
      malignancy, in their nuclei. An optical implementation of the hit-miss transform
      algorithm uses an analog spatial light modulator for gray-scale modulation at the
      filter plane of a 4f optical correlator. Gray-scale modulation at the filter
      plane improves correlator performance in comparison with a binary phase-only
      filter (BPOF) by reduction of the edge enhancement of kernels used in
      morphological detection of cancerous cervical cells. The hit-miss transform with
      a gray-scale amplitude and binary phase optical filter (GABPOF) for the hit
      filter and a BPOF for the miss filter shows a 47% reduction in total error versus
      the use of only BPOF filters to locate abnormal cells.

PMID- 18337958
TI  - Transient optical modulation with a disperse-red-1-doped polymer film.
AB  - Transient optical modulation properties of a disperse-red-1-doped polymer film
      are investigated by use of four-wave mixing with two-color light. Interesting
      behavior is observed for the transient modulation on variation of the two-color
      light intensities because of competition between the two mechanisms of one-photon
      (reorientation) and biphoton (isomerization) gratings. Positive and negative
      modulation as well as double-frequency modulation relative to blue-light input is
      observed in the experiment. The results may have applications in optical
      information processing.

PMID- 18337959
TI  - Equivalency-processing parallel photonic integrated circuit (EP3IC): equivalence
      search module based on multiwavelength guided-wave technology.
AB  - We present an optoelectronic module called the equivalency-processing parallel
      photonic integrated circuit (EP(3)IC) that is created specifically to implement
      high-speed parallel equivalence searches (i.e., database word searches). The
      module combines a parallel-computation model with multiwavelength photonic
      integrated-circuit technology to achieve high-speed data processing. On the basis
      of simulation and initial analytical computation, a single-step multicomparand
      word-parallel bit-parallel equality search can attain an aggregate processing
      speed of 82 Tbit/s. We outline the theoretical design of the monolithic module
      and the integrated components and compare this with a functionally identical bulk
      optics implementation. This integrated-circuit solution provides relatively low
      power operation, fast switching speed, a compact system footprint, vibration
      tolerance, and ease of manufacturing.

PMID- 18337960
TI  - Optical implementation of asynchronous-transfer-mode header-error control.
AB  - The asynchronous transfer mode (ATM) is a promising technique for broadband
      switching that is capable of supporting high-bit-rate multimedia services.
      Progress in all-optical parallel processing shows that photonics may be used in
      the future in full-functionality ATM switching nodes. All-optical switching
      fabrics and buffers have already been demonstrated. Fewer studies have been
      dedicated to ATM header-processing functions. As an example of photonic header
      processing, the implementation of a header-error control (HEC) subsystem by means
      of an optical circuit is investigated. Although traditional electronic decoders
      perform HEC in a serial mode, the architecture chosen for the optical HEC
      subsystem is based on parallelism, and an appropriate parallel-decoding algorithm
      was used in designing it.

PMID- 18337961
TI  - Focal-plane processing architectures for real-time hyperspectral image
      processing.
AB  - Real-time image processing requires high computational and I/O throughputs
      obtained by use of optoelectronic system solutions. A novel architecture that
      uses focal-plane optoelectronic-area I/O with a fine-grain, low-memory, single
      instruction-multiple-data (SIMD) processor array is presented as an efficient
      computational solution for real-time hyperspectral image processing. The
      architecture is evaluated by use of realistic workloads to determine data
      throughputs, processing demands, and storage requirements. We show that
      traditional store-and-process system performance is inadequate for this
      application domain, whereas the focal-plane SIMD architecture is capable of
      supporting real-time performances with sustained operation throughputs of 500
      1500 gigaoperations/s. The focal-plane architecture exploits the direct coupling
      between sensor and parallel-processor arrays to alleviate data-bandwidth
      requirements, allowing computation to be performed in a stream-parallel
      computation model, while data arrive from the sensors.

PMID- 18337962
TI  - Statistical-uncertainty-based adaptive filtering of lidar signals.
AB  - An adaptive filter signal processing technique is developed to overcome the
      problem of Raman lidar water-vapor mixing ratio (the ratio of the water-vapor
      density to the dry-air density) with a highly variable statistical uncertainty
      that increases with decreasing photomultiplier-tube signal strength and masks the
      true desired water-vapor structure. The technique, applied to horizontal scans,
      assumes only statistical horizontal homogeneity. The result is a variable spatial
      resolution water-vapor signal with a constant variance out to a range limit set
      by a specified signal-to-noise ratio. The technique was applied to Raman water
      vapor lidar data obtained at a coastal pier site together with in situ
      instruments located 320 m from the lidar. The micrometeorological humidity data
      were used to calibrate the ratio of the lidar gains of the H(2)O and the N(2)
      photomultiplier tubes and set the water-vapor mixing ratio variance for the
      adaptive filter. For the coastal experiment the effective limit of the lidar
      range was found to be approximately 200 m for a maximum noise-to-signal variance
      ratio of 0.1 with the implemented data-reduction procedure. The technique can be
      adapted to off-horizontal scans with a small reduction in the constraints and is
      also applicable to other remote-sensing devices that exhibit the same inherent
      range-dependent signal-to-noise ratio problem.

PMID- 18337963
TI  - Measurement of low-altitude infrared propagation.
AB  - Infrared propagation at low altitudes is determined by extinction that is due to
      molecules and aerosol particles and ray bending by refraction, three effects that
      control the mean value of the signal. Interference causes the signal to
      fluctuate, or scintillate, about the mean value. We discuss the design,
      calibration, and limitations of a field instrument for measuring optical
      propagation inside the midwave and long-wave infrared atmospheric windows. The
      instrument, which is accurate to ?10%, has been used to investigate aerosol,
      refractive, and scintillation phenomena in the marine boundary layer.

PMID- 18337964
TI  - Atmospheric correction algorithm for hyperspectral remote sensing of ocean color
      from space.
AB  - Existing atmospheric correction algorithms for multichannel remote sensing of
      ocean color from space were designed for retrieving water-leaving radiances in
      the visible over clear deep ocean areas and cannot easily be modified for
      retrievals over turbid coastal waters. We have developed an atmospheric
      correction algorithm for hyperspectral remote sensing of ocean color with the
      near-future Coastal Ocean Imaging Spectrometer. The algorithm uses look-up tables
      generated with a vector radiative transfer code. Aerosol parameters are
      determined by a spectrum-matching technique that uses channels located at
      wavelengths longer than 0.86 mum. The aerosol information is extracted back to
      the visible based on aerosol models during the retrieval of water-leaving
      radiances. Quite reasonable water-leaving radiances have been obtained when our
      algorithm was applied to process hyperspectral imaging data acquired with an
      airborne imaging spectrometer.

PMID- 18337965
TI  - Atmospheric correction of SeaWiFS imagery for turbid coastal and inland waters.
AB  - The standard SeaWiFS atmospheric correction algorithm, designed for open ocean
      water, has been extended for use over turbid coastal and inland waters. Failure
      of the standard algorithm over turbid waters can be attributed to invalid
      assumptions of zero water-leaving radiance for the near-infrared bands at 765 and
      865 nm. In the present study these assumptions are replaced by the assumptions of
      spatial homogeneity of the 765:865-nm ratios for aerosol reflectance and for
      water-leaving reflectance. These two ratios are imposed as calibration parameters
      after inspection of the Rayleigh-corrected reflectance scatterplot. The
      performance of the new algorithm is demonstrated for imagery of Belgian coastal
      waters and yields physically realistic water-leaving radiance spectra. A
      preliminary comparison with in situ radiance spectra for the Dutch Lake
      Markermeer shows significant improvement over the standard atmospheric correction
      algorithm. An analysis is made of the sensitivity of results to the choice of
      calibration parameters, and perspectives for application of the method to other
      sensors are briefly discussed.

PMID- 18337966
TI  - Wide-angle narrow-bandpass optical detection system optimally designed to have a
      large signal-to-noise ratio.
AB  - A method for achieving optimal design of a wide-angle narrow-bandpass optical
      detection system composed of a spherical interference filter and a circular
      photodetector is introduced. It was found that there is an optimal photodetector
      diameter that maximizes the signal-to-noise ratio (SNR) for a given filter
      configuration. We show how to optimize optical detection systems based on
      spherical interference filters for all the important parameters simultaneously.
      The SNR values of these systems are compared with the SNR values of spherical
      step-filter-based detection systems. When large silicon photodetectors are used,
      the two systems have equal SNR values so that the more economical step-filter
      systems are preferable. The results given here in the near-infrared region can be
      used for the optimization of any configuration of a detection system based on a
      spherical interference filter and a silicon photodetector working at the same
      wavelength range, without further calculations.

PMID- 18337967
TI  - Micromechanics-based wavelength-sensitive photonic beam control architectures and
      applications.
AB  - Micromechanics-based wavelength-sensitive photonic delay and amplitude control
      modules are introduced for multiwavelength photonic applications such as hardware
      compressed beam forming in phased-array antennas, timing-error compensation in
      high-speed long-haul fiber-optic communication networks, and pulse
      synchronization in photonic analog-to-digital converters and space-time code
      division multiplexed decoders. The basic delay structure relies on a single
      circulator compact reflective parallel path design that features polarization
      insensitivity, independently controllable optical time-delay and amplitude
      settings, and fiber compatibility. Switched fiber time delays are proposed that
      use various micromechanical mechanisms such as mechanically stretched fiber Bragg
      gratings with comb-drive translational stages or magnetic levitation-based
      stretchers. Additional, shorter-duration variable time delays are obtained by
      means of the translational motion of external mirrors and the inherent delays in
      the zigzag reflective path geometry of the bulk-optic thin-film interference
      filter-based wavelength multiplexer used in our proposed design. Experiments are
      performed to test these concepts.

PMID- 18337968
TI  - Modal field deformation and transition losses in UV side-written optical fibers.
AB  - The asymmetry of the UV-induced refractive-index profile in photosensitive
      optical fibers causes a deformation of the modal fields, resulting in transition
      losses between UV-exposed and unexposed fiber sections up to 0.1 dB for UV
      induced index changes of the order of <or=10(-2). A numerical analysis of the
      transition losses is developed. It is verified experimentally that the loss is
      caused by coupling of power of the fundamental mode to cladding modes at such a
      transition.

PMID- 18337969
TI  - Passive device based on plastic optical fibers to determine the indices of
      refraction of liquids.
AB  - We have designed and measured a passive device based on plastic optical fibers
      (POF's) that one can use to determine the indices of refraction of liquids. A
      complementary software has also been designed to simulate the behavior of the
      device. We report on the theoretical model developed for the device, its
      implementation in a simulation software program, and the results of the
      simulation. A comparison of the experimental and calculated results is also shown
      and discussed.

PMID- 18337970
TI  - Importance of chromophore environment on the near-infrared absorption of
      polymeric waveguides.
AB  - The near-infrared absorption of two chromophore functionalized polymers and
      combinations of seventeen different guest chromophores in seven different organic
      polymer matrices were investigated to assess the effect of chromophore structure
      and environment on absorption. The near-infrared absorption losses were found to
      be dramatically larger by as much as 2-3 orders of magnitude in polymer matrices
      than in solution. Furthermore, the absorption of the long-wavelength tail appears
      to be related to the glass transition temperature of the polymer matrix that
      contains the chromophore. These results are interpreted in terms of inhomogeneous
      broadening.

PMID- 18337971
TI  - Analysis of a dephased complex-coupled distributed-feedback laser by the power
      series method.
AB  - A novel power-series method to solve the coupled-wave equations is introduced.
      The method is used to calculate the threshold gain margins of a complex-coupled
      distributed-feedback laser as functions of the ratio of gain coupling to index
      coupling (|kappa(g)|/|kappa(n)|) and of the phase difference between the index
      and the gain gratings. For coupling coefficient |kappa|l < ., the laser shows a
      mode degeneracy at specific values of the ratio |kappa(g)|/|kappa(n)| for cleaved
      facets. At phase differences pi/2 and 3pi/2 between the gain and the index
      gratings, an antireflection-coated complex-coupled laser becomes multimode, and a
      different mode starts to lase. The effect of facet reflectivity (both magnitude
      and phase) on the gain margin of a complex-coupled DFB laser is also
      investigated. Although the gain margin varies slowly with the magnitude of the
      facet's reflectivity, it shows large variations as a function of the phase.
      Spatial hole burning was found to be minimum at phase difference npi, n =, ...,
      and maximum at phase differences pi/2 and 3pi/2.

PMID- 18337972
TI  - Flight qualification of a diode laser for path difference determination of a high
      resolution fourier transform spectrometer.
AB  - Diode lasers offer a lightweight, rugged, and economic alternative to other types
      of laser source, but they often do not provide long-term stability and spectral
      purity of emission. We have developed a stabilized, near-infrared diode laser
      source that is capable of as much as 20 mW of single-mode output power for the
      effective replacement of a He-Ne laser in the path difference measuring system of
      a high-resolution (1.25-m maximum path difference) Fourier transform
      spectrometer. Laser characterization has been performed both in laboratory
      measurements and in flight tests, resulting in a relative frequency stability of
      better than 10(-6) on a 6-h flight.

PMID- 18337973
TI  - Theoretical investigation of quasi-three-level longitudinally pumped continuous
      wave lasers.
AB  - A new theoretical derivation that makes it possible to compute the performance of
      a quasi-three-level longitudinally pumped cw laser is proposed. This theory,
      which takes into account the laser wave amplification and the pump wave
      absorption saturation coupling, seems simpler and more accurate than what has
      been previously published. The model accounts for single-pass, double-pass, and
      resonant pumping and can be used to characterize the thermal effect in the gain
      medium. It is also well suited for designing and optimizing such lasers. As an
      example, the theory is applied to the well-known Yb:YAG gain medium.

PMID- 18337974
TI  - Polarization effects in a high-birefringence elliptical fiber laser with a Bragg
      grating in a low-birefringence fiber.
AB  - The polarization characteristics of a fiber laser cavity that combines a high
      birefringence Er(3+)-doped elliptical core fiber with a Bragg grating fabricated
      in a low-birefringence (Low-Bi) fiber are studied. It is shown that, by use of an
      adequate length of Low-Bi fiber and an intracavity polarization controller, the
      dependence of the fiber laser's state of polarization on the pump's state of
      polarization can be altered. This fiber laser cavity design allows for the
      realization of a double-frequency, orthogonally polarized single-mode fiber laser
      source insensitive to the polarization parameters of the pump source.

PMID- 18337975
TI  - Fluorescence feedback control of an active Q-switched diode-pumped Nd:YVO4 laser.
AB  - We have implemented active feedback control in a Q-switched diode-pumped
      Nd:YVO(4) laser by monitoring the fluorescence intensity from the laser crystal.
      When the initial inversion level indicated by the detected fluorescence has
      reached a predetermined value, Q switching is initiated. This scheme allowed us
      to vary the reproducibility of the output pulse peak power and pulse width. The
      novel active Q-switching approach can reduce the shot-to-shot variations of the
      output pulse peak power and the pulse width.

PMID- 18337976
TI  - Gain saturation measurements of ytterbium-doped Sr5(PO4)3 F.
AB  - We report on the experimental measurement of the saturated gain of
      Yb(3+):Sr(5)(PO(4))(3)F at the 1047-nm laser line as a function of pump fluence
      and probe energy. The emission line was accurately modeled as a single
      homogeneous extraction, yielding values of 6.2 x 10(-20) cm(2) for the emission
      cross section and 3.3 J/cm(2) for the saturation fluence.

PMID- 18337977
TI  - Improved pump-beam distribution in a diode side-pumped solid-state laser with a
      highly diffuse, cross-axis beam delivery system.
AB  - A new cavity for diode side-pumped solid-state lasers was designed, built, and
      tested. The results were efficient absorption of pumped light in the media and
      homogeneous pumped-beam distribution under various pump-power levels, which
      generated Nd:YAG active media of different radii and concentrations and shifts of
      the diode wavelength. Full-multimode quasi-continuous pump operation with a slope
      efficiency of 40.5% was obtained from a plane-plane resonator equipped with two
      Nd:YAG rods. At a maximum average pump power of 1.33 kW, the optical-to-optical
      efficiency was 31.4%. Single-transverse-mode operation (M(2) factor of less than
      1.1) of 163 W was demonstrated.

PMID- 18337978
TI  - Comment on "Theory of the double-edge molecular technique for Doppler lidar wind
      measurement".
AB  - A theory of the double-edge technique for lidar measurement of wind speed Doppler
      shifts was recently presented by Flesia and Korb [Appl. Opt. 38, 432 (1999)]. It
      is shown here that the technique proposed by Flesia and Korb to achieve equal
      responsivity to aerosol and Rayleigh backscatter signals was previously conceived
      and demonstrated by another group.

PMID- 18337979
TI  - Line-pair selections for remote sensing of atmospheric ammonia by use of a
      coherent CO2 differential absorption lidar system.
AB  - Research on wavelength selection of CO2 laser lines for range-resolved remote
      sensing of atmospheric ammonia by use of a coherent differential absorption lidar
      system is described. Four laser line pairs are suggested for different levels of
      ammonia concentrations from approximately a few parts per billion to 1 part per
      million in a polluted atmosphere. The most suitable line for measuring ambient
      ammonia concentrations is 9R(30), because it has the highest absorption
      coefficient. 10R(14) has the lowest absorption coefficient, making it suitable
      for strong source mapping. 10R(8) and 10P(32) are best for intermediate levels of
      ammonia concentration. Absorption coefficients of ammonia calculated from the
      HITRAN96 database are in good agreement (mostly within +/-10% )with other
      experimental results.Sensitivity of measurement, interference from water-vapor
      lines with typical humidity in the summer,and sensitivity of ammonia absorption
      cross section to temperature and pressure are analyzed and calculated for the
      four wavelength pairs. The results show that the interference from water-vapor
      lines is easily correctable to a negligible amount, and errors caused by
      uncertainties in temperature and pressure are insignificant.

PMID- 18337980
TI  - Localized approximation for gaussian beams in elliptical cylinder coordinates.
AB  - We establish a localized approximation to evaluate the beam-shape coefficients of
      a Gaussian beam in elliptical cylinder coordinates. As for the case of spherical
      coordinates and of circular cylinder coordinates, this approximation provides an
      efficient way to speed up computations within the framework of a generalized
      Lorenz-Mie theory for elliptical cylinders.

PMID- 18337981
TI  - Calculation of the amplitude matrix for a nonspherical particle in a fixed
      orientation.
AB  - General equations are derived for computing the amplitude matrix for a
      nonspherical particle in an arbitrary orientation and for arbitrary illumination
      and scattering directions with respect to the laboratory reference frame,
      provided that the scattering problem can be solved with respect to the particle
      reference frame. These equations are used along with the T-matrix method to
      provide benchmark results for homogeneous, dielectric, rotationally symmetric
      particles. The computer code is publicly available on the World-Wide Web at
      http://www.giss.nasa.gov/~crmim.

PMID- 18337982
TI  - Pulsed indirect photoacoustic spectroscopy: application to remote detection of
      condensed phases.
AB  - The technique of pulsed indirect photoacoustic spectroscopy is applied to the
      examination of free liquid surfaces, and the prospects are assessed for remote
      detection and identification of chemical species in a field environment. A CO(2)
      laser (tunable within the 9-11-microm region) provides pulsed excitation for a
      variety of sample types; the resulting photoacoustic pulses are detected at
      ranges of the order of a few centimeters. The phenomenon is investigated as a
      function of parameters such as temperature, sample depth, laser-pulse energy,
      pulse length, and beam diameter. The results are in good agreement with a
      theoretical model that assumes the mechanism to be expansion of air resulting
      from heat conduction from the laser-heated surface of the sample under
      investigation. Signal and noise processing issues are discussed briefly, and the
      possible extension of the technique to ranges of the order of 10 m is assessed.

PMID- 18337983
TI  - Investigation of two-photon-induced polarization spectroscopy of the a-X (1,0)
      transition in molecular nitrogen at elevated pressures.
AB  - Two-photon-induced polarization spectroscopy of molecular nitrogen in the alpha
      1IIg(nu' =) <-- X 1Sigma(g)+ (nu" =) system near 283 nm was performed, and its
      signal dependence investigated over the pressure range from 1.2 to 5 bars at 300
      K. A significant increase of the signal intensity with pressure beyond the
      expected square law for a two-photon process was observed for pure nitrogen.
      Similar behavior was also found for a constant nitrogen partial pressure with
      increasing partial pressures of argon buffer gas. In both cases the spectral
      linewidth of the excited transitions increased dramatically with overall
      pressure. A possible explanation is given for the observed behavior in terms of
      contributions to the nonlinear susceptibility of the medium from the population
      of one-photon resonantly absorbing excited-state nitrogen and ground state
      N(2)(+) ions created in the multiphoton absorption process at the high laser
      intensities required.

PMID- 18337984
TI  - Low-frequency wavelength modulation spectroscopy with D2 transition of atomic
      cesium by use of an external-cavity diode laser.
AB  - Low-frequency wavelength modulation spectroscopy is acquired with an external
      cavity diode laser. The wavelength modulation is achieved with voltage tuning by
      means of scanning with the piezoelectric stepper motor, which rotates the end
      mirror in the laser cavity. With optimum 1-kHz frequency modulation and harmonic
      detection, direct absorption experiments for the 6S(1/2)(F = 4) --> 6P(3/2)
      transition of the cesium D(2) line were carried out. We found that 6f-harmonic
      detection is best here with a signal-to-noise voltage ratio of 460.

PMID- 18337985
TI  - Application of in situ ellipsometry in the fabrication of thin-film optical
      coatings on semiconductors.
AB  - Thin-film interference filters, suitable for use on GaAs- and InP-based lasers,
      have been fabricated by use of the electron-cyclotron resonance plasma-enhanced
      chemical vapor deposition technique. Multilayer film structures composed of
      silicon oxynitride material have been deposited at low temperatures with an in
      situ rotating compensator ellipsometer for monitoring the index of refraction and
      thickness of the deposited layers. Individual layers with an index of refraction
      from 3.3 to 1.46 at 633 nm have been produced with a run-to-run reproducibility
      of 0.005 and a thickness control of 10 A. Several filter designs have been
      implemented, including high-reflection filters, one- and two-layer anitreflection
      filters, and narrow-band high-reflection filters. It is shown that an accurate
      measurement of the filter optical properties during deposition is possible and
      that controlled reflectance spectra can be obtained.

PMID- 18337986
TI  - Diffraction of x rays in capillary optics.
AB  - Propagation of x rays generated by a small-diameter incoherent source through the
      capillary waveguide that satisfies the multimode condition is studied with the
      Fresnel-Kirchhoff diffraction theory. The strong influence of diffraction on the
      propagation is demonstrated. The diffraction phenomenon is manifested by the
      appearance of diffraction fringes in both the guide channel and the far-field
      zone of the capillary output. Experimental data that confirm such behavior of the
      x-ray radiation is also presented. The results confirm the interference effects
      recently observed in some experiments on the grazing reflections of x rays in
      single- and multiple-capillary optics.

PMID- 18337987
TI  - Modeling and observations of phase-mask trapezoidal profiles with grating-fiber
      image reproduction.
AB  - We report on an investigation of the trapezoidal design and fabrication defects
      in phase masks used to produce Bragg reflection gratings in optical fibers. We
      used a direct visualization technique to examine the nonuniformity of the
      interference patterns generated by several phase masks. Fringe patterns from the
      phase masks are compared with the analogous patterns resulting from two-beam
      interference. Atomic force microscope imaging of the actual phase gratings that
      give rise to anomalous fringe patterns is used to determine input parameters for
      a general theoretical model. Phase masks with pitches of 0.566 and 1.059 microm
      are modeled and investigated.

PMID- 18337988
TI  - Off-axis pivot mounting for aberration-corrected concave gratings at normal
      incidence.
AB  - The off-axis pivot-point mounting for toroidal uniform line-space (TULS) gratings
      and spherical varied line-space (SVLS) is presented: One scans the spectrum by
      rotating the grating about the pivot point. The best choice for the location of
      the point is discussed: For a monochromator the location is chosen such that the
      grating is moved approximately along the bisector of the subtended angle; for a
      spectrometer, it is chosen such that the grating is moved approximately along the
      direction of the incident ray. Minimizing the spectral defocusing caused by the
      rotation of the grating determines the optimum length of the pivot arm. The pivot
      points for TULS and SVLS gratings are found to be located on opposite sides with
      respect to the normal to the grating. In a comparison of the optical performance,
      the spectral focusing is similar, but the spatial aberrations can be fewer for a
      SVLS grating.

PMID- 18337989
TI  - Fabrication and testing of chemically micromachined silicon echelle gratings.
AB  - We have fabricated large, coarsely ruled, echelle patterns on silicon wafers by
      using photolithography and chemical-etching techniques. The grating patterns
      consist of 142-microm-wide, V-shaped grooves with an opening angle of 70.6
      degrees, blazed at 54.7 degrees. We present a detailed description of our grating
      fabrication techniques and the results of extensive testing. We have measured
      peak diffraction efficiencies of 70% at lambda = 632.8 nm and conclude that the
      gratings produced by our method are of sufficient quality for use in high
      resolution spectrographs in the visible and near IR (lambda approximately = 500
      5000 nm).

PMID- 18337990
TI  - Fiber bragg grating strain sensor demodulation with quadrature sampling of a mach
      zehnder interferometer.
AB  - A simple and highly sensitive phase-demodulation technique is proposed, and its
      use for a fiber Bragg grating strain sensor is experimentally demonstrated.
      Sampling a phase-modulated Mach-Zehnder output with controlled time delay
      produced two quadrature data streams that have relative quadrature phase
      difference (90 degrees ). The Bragg wavelength-dependent phase information is
      extracted by application of digital arctangent function and phase unwrapping to
      the quadrature signals. By use of this technique with a reference grating, strain
      sensing at as much as a 30-kHz sampling rate was obtained with strain resolution
      of 3.5 microstrains and 6 nanostrains/[square root]Hz in quasi-static and dynamic
      strain measurements, respectively.

PMID- 18337991
TI  - Application of a mid-infrared fiber bundle in remote measurement of gas
      concentrations in a chemical vapor deposition chamber.
AB  - A fiber bundle has been designed for measurement of gas concentrations in a
      chemical vapor deposition (CVD) chamber. The bundle is broadband, covering the
      spectrum range from 500 to 6000 cm(-1). Using this bundle, we have designed
      Fourier Transform infrared (FTIR) sampling configurations with reduced beam
      divergence (from 0.4 to 0.1 rad) and focal spot diameters (from 12 to 4 mm). The
      FTIR spectrum of tetraethoxysilane vapors in a CVD chamber was determined with
      the bundle and modified SAM connectors. An ellipsoid reflector was designed that
      yielded improved signal-to-noise ratios (SNR's) in the fiber-based spectra by a
      factor of 2. The incorporation of this reflector in spectrometers by use of the
      fiber bundle has the potential to reduce the sampling times for spectra while
      retaining acceptable SNR's.

PMID- 18337992
TI  - Simultaneous measurement of strain and temperature by use of a single fiber Bragg
      grating written in an erbium:ytterbium-doped fiber.
AB  - We demonstrate a fiber-optic sensor scheme, capable of the simultaneous
      measurement of strain and temperature with a single fiber Bragg grating written
      in an erbium:ytterbium-doped fiber. This compact fiber-grating-based sensor
      scheme, believed to be novel, can be used for synchronous measurement of strain
      and temperature over ranges of 1100 microepsilon and 50-180 degrees C with rms
      errors of 55.8 microepsilon and 3 degrees C, respectively. The simple and low
      cost sensor approach has a considerable potential, particularly for wide-range
      strain-sensing applications in which high resolution is not required.

PMID- 18337993
TI  - Enhanced optical microlithography with a Fabry-Perot-based spatial filtering
      technique.
AB  - A coherent multiple imaging technique for use in optical microlithography was
      studied. The technique involves placing a thin Fabry-Perot etalon between the
      mask and the projection lens of an optical stepper. An optical lithographic
      computer simulation tool, Prolith/2, was used to evaluate the aerial image
      profile obtained for extended mask structures such as typical contact hole arrays
      and line-space patterns used in integrated circuit fabrication. Additionally, a
      set of experimental studies were performed to validate the simulation results.
      Enhancement of both resolution and depth of focus can be obtained simultaneously
      with appropriate etalon parameters.

PMID- 18337994
TI  - Contactless optoelectronic technique for monitoring epoxy cure.
AB  - We describe a novel noninvasive optical technique to monitor the refractive-index
      variation in an epoxy-based resin that is due to the polymerization process. This
      kind of resin is widely used in polymer matrix composites. It is well known that
      the process of fabricating a thermoset-based composite involves mass and heat
      transfer coupled with irreversible chemical reactions that induce physical
      changes. To improve the quality and the reliability of these materials,
      monitoring the cure and optimization of the manufacturing process are of key
      importance. We discuss the basic operating principles of an optical system based
      on angle deflection measurements and present typical cure-monitoring results
      obtained from optical characterization. The method provides a flexible, high
      sensitivity, material-independent, low-cost, noninvasive tool for monitoring real
      time refractive-index variation.

PMID- 18337995
TI  - Aberration measurement from specific photolithographic images: a different
      approach.
AB  - Techniques for measurement of higher-order aberrations of a projection optical
      system in photolithographic exposure tools have been established. Even-type and
      odd-type aberrations are independently obtained from printed grating patterns on
      a wafer by three-beam interference under highly coherent illumination. Even-type
      aberrations, i.e., spherical aberration and astigmatism, are derived from the
      best focus positions of vertical, horizontal, and oblique grating patterns by an
      optical microscope. Odd-type aberrations, i.e., coma and three-foil, are obtained
      by detection of relative shifts of a fine grating pattern to a large pattern by
      an overlay inspection tool. Quantitative diagnosis of lens aberrations with a
      krypton fluoride (KrF) excimer laser scanner is demonstrated.

PMID- 18337996
TI  - Single aspherical lens for deastigmatism, collimation, and circularization of a
      laser beam.
AB  - An astigmatic and elliptically diverging laser beam generated by a gain-guided
      laser diode can be converted into a collimated and circular beam with a single
      specially designed lens. The designed lens also corrects for the astigmatism
      present in the laser diode. The input surface of the lens has a different concave
      and convex aspherical profile in the transverse and the longitudinal direction,
      respectively, for astigmatism correction. The output surface possesses a convex
      aspherical and a straight profile in the transverse and the longitudinal
      direction, respectively, for collimation and circularization of the final output
      laser beam.

PMID- 18337997
TI  - Faceted concentrators optimized for homogeneous radiation.
AB  - For technical reasons, large three-dimensional compound parabolic concentrators
      (CPC's) are often built from facets with either no or only one-dimensional
      curvature. We analyze CPC approximations made with various numbers of axial and
      circumferential subdivisions. Incident radiation within half-angles of 10 degrees
      and 30 degrees is considered. The reflectivity of the mirrors is assumed to be
      90% or 95%. The performance of faceted concentrators can be significantly
      improved by optimization as compared with heuristic CPC approaches. The highest
      increase in transmission that we observed was 19% greater as compared with that
      of a heuristic CPC approximation. The shapes of the optimized concentrators
      differ from that of a classic CPC, and most of the optimized concentrators are
      longer than a classic CPC. For practical concentrators with a small number of
      facets, the optimized geometry provides better performance than a heuristic
      approximation of the CPC shape.

PMID- 18337998
TI  - High-efficiency micro-optical color filter for liquid-crystal projection system
      applications.
AB  - High-efficiency color filters composed of a microprism array, optical
      interference color filters, and a microlens array light compressor were developed
      to increase the optical throughput of liquid-crystal projection systems. The new
      devices utilize the energy of whole spectra by taking full advantage of a light
      compressor and interference dichroic filters to distribute the energy of spectra
      to the respective color pixel area. Thus high-efficiency micro-optical color
      filters allow efficient utilization of the energy of incident light and maximize
      the optical throughput of the projection system.

PMID- 18337999
TI  - Pockels cell voltage probe for noninvasive electron-beam measurements.
AB  - Accurate measurements of beam position and current are critical for the operation
      of the high-energy electron accelerators used for radiographic applications.
      Traditional short-pulse (e.g., 70 ns) machines utilize B-dot loops to monitor
      these parameters with great success. For long-pulse (e.g., 2 micros)
      accelerators, beam position and current measurements become more challenging and
      may require new technology. A novel electro-optic voltage probe has been
      developed for this application and provides the advantages of complete galvanic
      isolation, excellent low-frequency performance, and no time integration
      requirement. The design of a prototype sensor is presented along with preliminary
      accelerator test data.

PMID- 18338000
TI  - Interphase in plasma-deposited films on plastics: effect on the spectral
      properties of optical filters.
AB  - The plasma-enhanced chemical vapor deposition of optical coatings on plastic
      substrates leads to the formation of a physically thick (approximately 50-100-nm)
      interfacial region (or interphase). We propose, based on our earlier
      spectroellipsometric (in situ and ex situ) and spectrophotometric (ex situ)
      studies, an optical model for the description of the interphase refractive-index
      profile n(z). We study in detail the effect of such an interphase on the spectral
      performance of various optical filters (antireflective V-coat, W-coat, achromatic
      W-coat, and minus filter). It is shown that considering the inhomogeneous n(z)
      profile in the design can improve the optical performance of some filters.

PMID- 18338001
TI  - Improved method for determination of optical constants of organic thin films from
      reflection and transmission measurements.
AB  - A new technique for determining the optical properties of organic thin films is
      presented. A detailed evaluation of the accuracy of the determined optical
      constants has been performed, and the best combination of measured values
      yielding the smallest errors in the index of refraction for realistic
      experimental uncertainties has been found. The proposed method utilizes the fact
      that optical constants are smooth continuous functions, which reduces the
      possibility of encountering multiple solutions. The method consists of two steps.
      In the first step the optical constants at all wavelengths and the film thickness
      are determined. In the second step the thickness and the imaginary part of the
      index of refraction are kept fixed while we reevaluate the real part of the index
      of refraction by using a different objective function with improved sensitivity
      to the refractive index. After verifying that the proposed method is capable of
      an accurate estimation of optical constants, we determine the index of refraction
      data of vanadyl-phthalocyanine in the visible spectral range.

PMID- 18338002
TI  - Effect of multiple light paths on retinal vessel oximetry.
AB  - Techniques for noninvasively measuring the oxygen saturation of blood in retinal
      arteries and veins are reported in the literature, but none have been
      sufficiently accurate and reliable for clinical use. Addressing the need for
      increased accuracy, we present a series of oximetric equations that explicitly
      consider the effects of backscattering by red blood cells and lateral diffusion
      of light in the ocular fundus. The equations are derived for the specific
      geometry of a scanning-beam retinal vessel oximeter; however, the results should
      also be applicable to photographic oximeters. We present in vitro and in vivo
      data that suggest the validity of these equations.

PMID- 18338003
TI  - Influence of optical properties on two-photon fluorescence imaging in turbid
      samples.
AB  - A numerical model was developed to simulate the effects of tissue optical
      properties, objective numerical aperture (N.A.), and instrument performance on
      two-photon-excited fluorescence imaging of turbid samples. Model data are
      compared with measurements of fluorescent microspheres in a tissuelike scattering
      phantom. Our results show that the measured two-photon-excited signal decays
      exponentially with increasing focal depth. The overall decay constant is a
      function of absorption and scattering parameters at both excitation and emission
      wavelengths. The generation of two-photon fluorescence is shown to be independent
      of the scattering anisotropy, g, except for g > 0.95. The N.A. for which the
      maximum signal is collected varies with depth, although this effect is not seen
      until the focal plane is greater than two scattering mean free paths into the
      sample. Overall, measurements and model results indicate that resolution in two
      photon microscopy is dependent solely on the ability to deliver sufficient
      ballistic photon density to the focal volume. As a result we show that lateral
      resolution in two-photon microscopy is largely unaffected by tissue optical
      properties in the range typically encountered in soft tissues, although the
      maximum imaging depth is strongly dependent on absorption and scattering
      coefficients, scattering anisotropy, and objective N.A..

PMID- 18338004
TI  - Multiple polynomial regression method for determination of biomedical optical
      properties from integrating sphere measurements.
AB  - We present a new, to our knowledge, method for extracting optical properties from
      integrating sphere measurements on thin biological samples. The method is based
      on multivariate calibration techniques involving Monte Carlo simulations,
      multiple polynomial regression, and a Newton-Raphson algorithm for solving
      nonlinear equation systems. Prediction tests with simulated data showed that the
      mean relative prediction error of the absorption and the reduced scattering
      coefficients within typical biological ranges were less than 0.3%. Similar tests
      with data from integrating sphere measurements on 20 dye-polystyrene microsphere
      phantoms led to mean errors less than 1.7% between predicted and theoretically
      calculated values. Comparisons showed that our method was more robust and
      typically 5-10 times as fast and accurate as two other established methods, i.e.,
      the inverse adding-doubling method and the Monte Carlo spline interpolation
      method.

PMID- 18338005
TI  - Design, fabrication, and performance of preferential-order volume grating
      waveguide couplers.
AB  - Both a nonfocusing and a focusing preferential-order volume grating waveguide
      coupler were designed, fabricated, and tested. These volume grating couplers are
      designed to outcouple a 633-nm wave guided in an adjacent polyimide waveguide
      film. The slanted-fringe volume gratings are recorded holographically by the
      interference of two 364-nm waves. The dynamics of the holographic photopolymer
      HRF600X001 are investigated in relation to the interaction with the guided wave.
      The fabricated couplers exhibited a preferential coupling of 98%, a spatial
      coupling rate of 3.6 mm(-1), and a coupling efficiency of 95%. The focusing
      grating coupler focused the outcoupled beam to a focal line with a full width at
      half-maximum of 10.49 microm located 25 mm above the grating.

PMID- 18338006
TI  - Gray-level computer-generated hologram filters for multiple-object correlation.
AB  - Synthesis of gray-level computer-generated holograms allows for an increase of
      the information storage capability that is usually achieved with conventional
      binary filters. This is mainly because more degrees of freedom are available. We
      propose to profit from this feature by synthesizing complex filters formed by
      many superimposed holograms, each with a different carrier frequency. We apply
      these gray-level filters to perform multichannel correlation and in this way
      enhance the capability of optical correlators to process the information in
      parallel and simultaneously. First, we analyze the behavior of some performance
      criteria on the impulse response and on the correlation as a function of the
      number of holograms that are multiplexed. Then we show the results of two
      experiments: In the first a composed phase-only filter is used in a multiple
      object recognition process. In the second a composed synthetic discriminant
      function filter is used to implement an object classification by means of a
      binary code.

PMID- 18338007
TI  - Scene-based nonuniformity correction with video sequences and registration.
AB  - We describe a new, to our knowledge, scene-based nonuniformity correction
      algorithm for array detectors. The algorithm relies on the ability to register a
      sequence of observed frames in the presence of the fixed-pattern noise caused by
      pixel-to-pixel nonuniformity. In low-to-moderate levels of nonuniformity,
      sufficiently accurate registration may be possible with standard scene-based
      registration techniques. If the registration is accurate, and motion exists
      between the frames, then groups of independent detectors can be identified that
      observe the same irradiance (or true scene value). These detector outputs are
      averaged to generate estimates of the true scene values. With these scene
      estimates, and the corresponding observed values through a given detector, a
      curve-fitting procedure is used to estimate the individual detector response
      parameters. These can then be used to correct for detector nonuniformity. The
      strength of the algorithm lies in its simplicity and low computational
      complexity. Experimental results, to illustrate the performance of the algorithm,
      include the use of visible-range imagery with simulated nonuniformity and
      infrared imagery with real nonuniformity.

PMID- 18338008
TI  - Three-dimensional pattern recognition with a single two-dimensional synthetic
      reference function.
AB  - A novel, to our knowledge, method of distortion-invariant three-dimensional (3-D)
      pattern recognition is proposed. A single two-dimensional synthetic discriminant
      function is employed as a reference function in the 3-D correlator. Thus the
      proposed system is able to identify and locate any true-class object in the 3-D
      scene. Preliminary simulation and experimental results are presented.

PMID- 18338009
TI  - Compensation method for attenuated planar laser images of optically dense sprays.
AB  - We present a method for compensating laser attenuation in optically dense sprays,
      in particular for use in combustion engine research. Images of the fuel sprays
      are produced by planar laser imaging, where Mie scattered light from a cross
      section of the spray is imaged onto a CCD camera. The compensation scheme is
      based on the Beer-Lambert law, which is used here to sum up the loss of light
      along the path of the laser in the image, and to compensate iteratively, pixel by
      pixel, for this loss.

PMID- 18338010
TI  - Extended scale-invariant pattern recognition with white-light illumination.
AB  - A previous method of obtaining scale-invariance detection with white-light
      illumination has been improved on. We were able to detect different scaled
      versions of the target up to a magnification factor equal to 2. We simultaneously
      detected several versions in the same scene, because each scale factor is
      codified in a different wavelength. Experimental results demonstrate the proposed
      technique and show the utility of the method.

PMID- 18338011
TI  - Three-dimensional reconstruction of dielectric objects by the coupled-dipole
      method.
AB  - We present an inversion procedure for electromagnetic scattering, based on the
      powerful and flexible technique called the coupled-dipole method combined with an
      optimization algorithm. This method permits us to realize imaging of dielectric
      objects whose dimensions are comparable with the incident wavelength and is shown
      to be efficient with corrupted data (scattered electric field). The feasibility
      of this method is shown in a synthetic example in which the scattered field is
      corrupted with Gaussian noise. Two methods are used to invert the scattered field
      to recover the refractive index of the medium: a conventional matrix inversion
      and an iterative method.

PMID- 18338012
TI  - Coherent and incoherent off-axis Hermite-Gaussian beam combinations.
AB  - A detailed study of the coherent and the incoherent combinations of two
      dimensional off-axis Hermite-Gaussian beams with rectangular symmetry is made.
      The closed-form propagation formulas of the resulting beam are derived, and the
      resulting beam quality in terms of the M(2) factor and power in the bucket is
      discussed and compared for the coherent and the incoherent combinations. In
      addition, it is shown that the resulting astigmatic beam can be symmetrized in
      the sense of the second-moment definition of beam width. However, the
      symmetrizing transformation of the resulting astigmatic beams is incomplete,
      because there exist different irradiance profiles.

PMID- 18338013
TI  - Fast algorithms for data reduction in modern optical three-dimensional profile
      measurement systems with MMX technology.
AB  - Confocal microscopy and white-light interferometry are two promising methods for
      the three-dimensional microstructure analysis of technical and biologic
      specimens. For both methods the specimen is scanned through the focus position by
      means of an actuator. A large series of intensity frames is acquired. These data
      are used for the final calculation of the topography. We demonstrate that the
      multimedia extended (MMX) instruction set, which is implemented in modern Intel
      microprocessors, can be used for effective real-time preprocessing and for fast
      evaluation algorithms. So this new technique enables the implementation of more
      complex algorithms with acceptable run times even on standard computer
      technology. The possibilities of the MMX instruction set are discussed for
      confocal microscopy and for white-light interferometry.

PMID- 18338014
TI  - Acoustically steered and rotated true-time-delay generator based on wavelength
      division multiplexing.
AB  - The acoustically steered and rotated (ASTRO) true-time-delay (TTD) generator,
      capable of two-dimensional (2D) multiple beam generation without causing
      extraneous beams, is described. It is based on wavelength-division multiplexing
      to encode and decode various linear chirp time delays with wavelengths. An array
      of equally spaced light stripes with linear chirp time delays among them is
      formed and is subsequently rotated to a desired angle by use of our nonmechanical
      acousto-optic dove prism, believed to be novel. Our architecture reduces hardware
      complexity significantly by avoiding redundancy in conventional TTD generators.
      Experimental results to prove the concept of 2D multiple beam generation are
      shown. Also, an extension of the system for bidirectional communications is
      proposed. Various technical issues for practical applications are discussed.

PMID- 18338015
TI  - Effects of an asymmetrically molded plastic objective lens on the push-pull
      tracking-error signal in an optical disk drive.
AB  - The effects of a plastic objective lens's astigmatism on the push-pull tracking
      error signal (TES) of an optical disk data storage system were investigated
      theoretically and experimentally. Astigmatism of plastic objective lenses arises
      commonly from the asymmetric deviation from their designed shape during the
      molding process. By carefully studying the aberration characteristics of the
      objective lens and including the astigmatism of the laser diode in the analysis,
      we can calculate the combined effects of astigmatism of these two components on
      the push-pull TES. It is found, from both the simulations and the experiments,
      that, by rotation of the objective lens about the optical axis, the peak-to-peak
      value of the push-pull TES varies with the lens's rotation angle, and a change as
      great as 340% in its value was observed in a given optical pickup.

PMID- 18338016
TI  - Device for magneto-optic signal detection with a small crystal prism.
AB  - A device made of a birefringent crystal for signal detection of magneto-optic
      (MO) disks is presented. The light beam from a MO disk is separated into two
      orthogonally polarized components at the surface of a birefringent prism. After
      these two components are reflected by the top and the bottom surfaces of the
      prism inside, at the detector they become sufficiently separated from each other
      for discrete detection, even though the prism is small. A method for calculating
      the light intensities and the positions of focused beams in a birefringent prism
      and the results of a fundamental experiment are presented.

PMID- 18338017
TI  - Optimized forward model and retrieval scheme for MIPAS near-real-time data
      processing.
AB  - An optimized code to perform the near-real-time retrieval of profiles of
      pressure, temperature, and volume mixing ratio (VMR) of five key species (O(3),
      H(2)O, HNO(3), CH(4), and N(2)O) from infrared limb spectra recorded by the
      Michelson Interferometer for Passive Atmospheric Sounding (MIPAS) experiment on
      board the European Space Agency (ESA) Environmental Satellite ENVISAT-1 was
      developed as part of a ESA-supported study. The implementation uses the global
      fit approach on selected narrow spectral intervals (microwindows) to retrieve
      each profile in sequence. The trade-off between run time and accuracy of the
      retrieval was optimized from both the physical and the mathematical points of
      view, with optimizations in the program structure, in the radiative transfer
      model, and in the computation of the retrieval Jacobian. The attained
      performances of the retrieval code are noise error on temperature <2 K at all the
      altitudes covered by the typical MIPAS scan (8-53 km with 3-km resolution), noise
      error on tangent pressure <3%, and noise error on VMR of the target species <5%
      at most of the altitudes covered by the standard MIPAS scan, with a total run
      time of less than 1 min on a modern workstation.

PMID- 18338018
TI  - Vertical attenuation coefficient of photosynthetically active radiation as a
      function of chlorophyll concentration and depth in case 1 waters.
AB  - Based on empirical relations found in the literature, relatively simple
      mathematical models of the average of the total absorption of seawater
      [a(T(z,Chl))], the chlorophyll-specific absorption coefficient of phytoplankton
      [a*(ph(z,Chl))], and the backscattering coefficient [b(b(Chl))], weighted by the
      in situ spectral distribution of photosynthetically active scalar irradiance
      (PAR), as functions of chlorophyll concentration and depth, were developed. The
      models for a(T(z,Chl)) and b(b(Chl)) can be used to calculate the coefficient of
      vertical attenuation of PAR [K(o(z,Chl))] and therefore to estimate the vertical
      profile of PAR as an input to algorithms for primary production. One application
      of a*(ph(z,Chl)) may be in the correction of the initial slope of the
      photosynthesis-irradiance curve [alpha*((z))] for the in situ spectral
      distribution of PAR and the package effect. Also, a*(ph(z,Chl)) may be used to
      calculate phi((z)), the in situ quantum yield of photosynthesis, from phi(max)
      and irradiance.

PMID- 18338019
TI  - Estimation of laser system pointing performance by use of statistics of return
      photons.
AB  - Strategic laser systems are subject to residual pointing errors arising from
      vibrations and atmospheric turbulence, estimates of which may allow improved
      system performance. Field data from the Air Force Research Laboratory Floodbeam
      Experiments suggested a linear relationship between the mean and standard
      deviation of the shot-by-shot signals and the jitter. An ideal analytic solution
      and Monte Carlo simulations confirmed this result for a relatively large number
      of returns. A refined approach using statistical chi(2) techniques, which
      simultaneously estimates jitter and boresight, was developed to address results
      from satellite passes with relatively few returns and provides excellent jitter
      and boresight predictions.

PMID- 18338020
TI  - Atmospheric temperature profiling in the presence of clouds with a pure
      rotational Raman lidar by use of an interference-filter-based polychromator.
AB  - A lidar polychromator design for the measurement of atmospheric temperature
      profiles in the presence of clouds with the rotational Raman method is presented.
      The design utilizes multicavity interference filters mounted sequentially at
      small angles of incidence. Characteristics of this design are high signal
      efficiency and adjustable center wavelengths of the filters combined with a
      stable and relatively simple experimental setup. High suppression of the elastic
      backscatter signal in the rotational Raman detection channels allows temperature
      measurements independent of the presence of thin clouds or aerosol layers; no
      influence of particle scattering on the lidar temperature profile was observed in
      clouds with a backscatter ratio of at least 45. The minimum integration time
      needed for temperature profiling with a statistical temperature error of +/-1 K
      at, e.g., 20-km height and 960-m height resolution is 1.5 h.

PMID- 18338021
TI  - Reduction of skylight reflection effects in the above-water measurement of
      diffuse marine reflectance: comment.
AB  - Use of a vertical polarizer has been suggested to reduce the effects of surface
      reflection in the above-water measurements of marine reflectance. We suggest
      using a similar technique for airborne or spaceborne sensors when atmospheric
      scattering adds its own polarization signature to the upwelling radiance. Our own
      theoretical sensitivity study supports the recommendation of Fougnie et al.
      [Appl. Opt. 38, 3844 (1999)] (40-50 degrees vertical angle and azimuth angle near
      135 degrees, polarizer parallel to the viewing plane) for above-water
      measurements. However, the optimal viewing directions (and the optimal
      orientation of the polarizer) change with altitude above the sea surface, solar
      angle, and atmospheric vertical optical structure. A polarization efficiency
      function is introduced, which shows the maximal possible polarization
      discrimination of the background radiation for an arbitrary altitude above the
      sea surface, viewing direction, and solar angle. Our comment is meant to
      encourage broader application of airborne and spaceborne polarization sensors in
      remote sensing of water and sea surface properties.

PMID- 18338022
TI  - Phase-demodulation error of a fiber-optic Fabry-Perot sensor with complex
      reflection coefficients.
AB  - The influence of reflector losses attracts little discussion in standard
      treatments of the Fabry-Perot interferometer yet may be an important factor
      contributing to errors in phase-stepped demodulation of fiber optic Fabry-Perot
      (FFP) sensors. We describe a general transfer function for FFP sensors with
      complex reflection coefficients and estimate systematic phase errors that arise
      when the asymmetry of the reflected fringe system is neglected, as is common in
      the literature. The measured asymmetric response of higher-finesse metal
      dielectric FFP constructions corroborates a model that predicts systematic phase
      errors of 0.06 rad in three-step demodulation of a low-finesse FFP sensor (R =
      0.05) with internal reflector losses of 25%.

PMID- 18338023
TI  - Fiber-optic voltage sensor based on a Bi12TiO20 crystal.
AB  - A fiber-optic voltage sensor based on the longitudinal Pockels effect in a
      Bi(12)TiO(20) crystal is described. The use of a special backreflecting prism as
      a phase-retarding element is shown to improve the sensitivity and temperature
      stability of the sensor. A comparison between the temperature properties of the
      glass backreflecting prism and that of a quarter-wave plate is derived. The
      sensor demonstrates temperature stability of +/-1.5% from -20 degrees C to 60
      degrees C and sensitivity of 0.145% per 1 V(rms) at 850 nm without the use of an
      additional temperature control channel.

PMID- 18338024
TI  - Fiber mode coupling in transmissive and reflective tilted fiber gratings.
AB  - Whereas core-mode reflection and core-mode-to-radiation-mode coupling in tilted
      fiber Bragg gratings is well understood, as is coupling between a core mode and
      higher-order core and cladding modes in untilted gratings, here we analyze in
      detail the coupling among core modes and cladding modes in reflective and
      transmissive tilted fiber gratings. We show that strong coupling between an
      LP(01) core mode and the exact (1m) cladding modes occurs in a transmissive
      tilted grating for nearly any tilt angle except angles close to 90 degrees,
      whereas the LP(01)-to-(lm) cladding mode coupling (l not equal 1) is appreciable
      only for tilt angles just below 90 degrees (approximately 88 degrees). In a
      reflective grating, strong coupling between the LP(01) core mode and the exact
      (1m) cladding modes occurs only for angles less than approximately 5 degrees,
      whereas coupling to (1m) cladding modes for m > 1 occurs only for angles greater
      than approximately 5 degrees. Coupling among bound core modes exhibits a similar
      behavior, except that in general the coupling is stronger. Experimentally we show
      coupling to both higher-order bound core modes and cladding modes in a
      transmissive tilted grating at visible and near-infrared wavelengths.

PMID- 18338025
TI  - Spatial filter pinhole development for the national ignition facility.
AB  - We present results from a major experimental effort to understand the behavior of
      spatial filter pinholes and to identify and demonstrate a pinhole that will meet
      the requirements of the National Ignition Facility (NIF). We find that pinhole
      performance depends significantly on geometry and material. Cone pinholes are
      found to stay open longer and to cause less backreflection than pinholes of more
      conventional geometry. We show that a +/-150-microrad stainless-steel cone
      pinhole will pass a full-energy NIF ignition pulse with required margins for
      misalignment and for smoothing by spectral dispersion. On the basis of a model
      fitted to experimental results, a +/-125-microrad stainless-steel cone pinhole is
      also projected to meet these requirements.

PMID- 18338026
TI  - Short-range verification experiment of a trial one-dimensional synthetic aperture
      infrared laser radar operated in the 10-microm band.
AB  - A trial one-dimensional (1-D) synthetic aperture infrared laser radar (SAILR)
      system for imaging static objects, with two CO(2) lasers as a transmitter and a
      local oscillator for heterodyne detection, was constructed. It has a single
      receiving aperture mounted on a linearly movable stage with a length of 1 m and a
      position accuracy of 1 microm. In an indoor short-range experiment to confirm the
      fundamental functions of the system and demonstrate its unique imaging process we
      succeeded in obtaining 1-D synthetic aperture images of close specular point
      targets with theoretically expected resolution.

PMID- 18338027
TI  - Self-aligned extended-cavity diode laser stabilized by the Zeeman effect on the
      cesium D2 line.
AB  - An extended-cavity diode laser at 852 nm has been built especially for the
      purpose of cooling and probing cesium atoms. It is a compact, self-aligned, and
      continuously tunable laser source having a 100-kHz linewidth and 60-mW output
      power. The electronic control of the laser frequency by the piezodriven external
      reflector covers a 4.5-kHz bandwidth, allowing full compensation of acoustic
      frequency noise without any adverse effect on the laser intensity noise. We
      locked this laser to Doppler-free resonances on the cesium D(2) line by using the
      Zeeman modulation technique, resulting in the frequency and the intensity of the
      laser beam being unmodulated. We also tuned the locked laser frequency over a
      span of 120 MHz by using the dc Zeeman effect to shift the F = 4-F' = 5 reference
      transition.

PMID- 18338028
TI  - Duty cycle ratio dependence on the performance of a q-switched laser with an Er3+
      Yb3+ codoped glass waveguide.
AB  - We examine the performance of a hybrid Q-switched LiNbO(3) and Er(3+)-Yb(3+)
      doped glass waveguide laser as a modulation function of the duty cycle ratio. As
      the duty cycle ratio decreases, the laser operates at higher peak power and pulse
      width. At low duty cycle ratio (<1%), we observe variations in the Q-switched
      pulse shape; while the laser produces 59-W and 200-ns pulses to a 1-kHz
      repetition rate for a 50% duty cycle, it yields 27-W and 100-ns pulses to a 10
      kHz repetition rate for a 0.01% duty cycle.

PMID- 18338029
TI  - Multiwatt High-Repetition-Rate 2-microm Output from an Intracavity KTiOPO(4)
      Optical Parametric Oscillator.
AB  - We have obtained 6.5 W of 2-mum output from a near-degenerate, type II KTiOPO(4)
      (KTP) optical parametric oscillator (OPO) pumped within the cavity of a Q
      switched diode-pumped Nd:YAG laser that operates at 3 kHz. We adopted the
      simplest configuration with a compact diode-pumped Nd:YAG module pumping the
      doubly resonant KTP OPO in its randomly polarized resonator with an acousto-optic
      Q switch. Attempts to increase the 2-mum output power by pumping this intracavity
      KTP OPO with a polarized laser beam by use of thermal birefringence compensation
      configurations are discussed.

PMID- 18338030
TI  - Demonstration of differential backscatter absorption gas imaging.
AB  - Backscatter absorption gas imaging (BAGI) is a technique that uses infrared
      active imaging to generate real-time video imagery of gas plumes. We describe a
      method that employs imaging at two wavelengths (absorbed and not absorbed by the
      gas to be detected) to allow wavelength-differential BAGI. From the frames
      collected at each wavelength, an absorbance image is created that displays the
      differential absorbance of the atmosphere between the imager and the backscatter
      surface. This is analogous to a two-dimensional topographic differential
      absorption lidar or differential optical absorption spectroscopy measurement. Gas
      plumes are displayed, but the topographic scene image is removed. This allows a
      more effective display of the plume image, thus ensuring detection under a wide
      variety of conditions. The instrument used to generate differential BAGI is
      described. Data generated by the instrument are presented and analyzed to
      estimate sensitivity.

PMID- 18338031
TI  - Monolithic folded resonator for evanescent wave cavity ringdown spectroscopy.
AB  - An optical resonator is characterized that employs both ultrahigh-reflective
      coated surfaces and total internal reflection to enable cavity ringdown
      spectroscopy of surfaces, films, and liquids. The monolithic folded design
      possesses a polarization-independent finesse that allows polarization-dependent
      phenomena, such as molecular orientation, to be probed. Although a restricted
      bandwidth (~15% of the design wavelength) results from use of reflective
      coatings, the resonator provides high sensitivity and facile operation. A minimum
      detectable absorption of 2.2 x 10(-6) was obtained for single laser shots by use
      of multimode excitation at 530 nm with an excimer-pumped, pulsed dye laser.

PMID- 18338032
TI  - Modifying ligand-induced and constitutive signaling of the human 5-HT4 receptor.
AB  - G protein-coupled receptors (GPCRs) signal through a limited number of G-protein
      pathways and play crucial roles in many biological processes. Studies of their in
      vivo functions have been hampered by the molecular and functional diversity of
      GPCRs and the paucity of ligands with specific signaling effects. To better
      compare the effects of activating different G-protein signaling pathways through
      ligand-induced or constitutive signaling, we developed a new series of RASSLs
      (receptors activated solely by synthetic ligands) that activate different G
      protein signaling pathways. These RASSLs are based on the human 5-HT(4b)
      receptor, a GPCR with high constitutive G(s) signaling and strong ligand-induced
      G-protein activation of the G(s) and G(s/q) pathways. The first receptor in this
      series, 5-HT(4)-D(100)A or Rs1 (RASSL serotonin 1), is not activated by its
      endogenous agonist, serotonin, but is selectively activated by the small
      synthetic molecules GR113808, GR125487, and RO110-0235. All agonists potently
      induced G(s) signaling, but only a few (e.g., zacopride) also induced signaling
      via the G(q) pathway. Zacopride-induced G(q) signaling was enhanced by replacing
      the C-terminus of Rs1 with the C-terminus of the human 5-HT(2C) receptor.
      Additional point mutations (D(66)A and D(66)N) blocked constitutive G(s)
      signaling and lowered ligand-induced G(q) signaling. Replacing the third
      intracellular loop of Rs1 with that of human 5-HT(1A) conferred ligand-mediated
      G(i) signaling. This G(i)-coupled RASSL, Rs1.3, exhibited no measurable signaling
      to the G(s) or G(q) pathway. These findings show that the signaling repertoire of
      Rs1 can be expanded and controlled by receptor engineering and drug selection.

PMID- 18338033
TI  - Nanocrystal-micelle: synthesis, self-assembly and application.
AB  - Nanocrystals (NCs) are one of the important building blocks for fabrication of
      nanostructured arrays for wide range of optical, electronic, magnetic, catalytic
      and biosensing applications. Here, our recent advances in the synthesis, self
      assembly and application of NC-micelles are highlighted. The NCs are encapsulated
      inside the core of surfactant micelles in a rapid, interfacially driven micro
      emulsion process. The flexible surface chemistry of the NC-micelles causes them
      to be water-soluble and allows further self-assembly into two- and three
      dimensional ordered arrays. The NC-micelles are biocompatible, of interest for
      bio-labeling. Finally, integration of the ordered arrays and charge transport
      property are discussed.

PMID- 18338034
TI  - Conformational control by 'zipping-up' an anion-binding unimolecular capsule.
AB  - A flexible capsule has been designed in which the anion-binding preorganisation
      is enhanced by a urea 'zipper'.

PMID- 18338035
TI  - Modifications in the chemical structure of Trojan carriers: impact on cargo
      delivery.
AB  - Carriers with linear or dendrimeric structures displaying different functional
      groups were synthesized and their delivery properties were studied.

PMID- 18338036
TI  - A new hybrid framework based on a 'superoctahedral' [V7O6F30](14-) polyanion.
AB  - Solvothermal synthesis has led to the isolation of an unusual hybrid framework
      solid [CH3NH3]8[Cu(Py)4]3[V7O6F30] in which the novel [V7O6F30](14-) polyanion is
      linked via [Cu(py)4]2+ moieties into a doubly interpenetrated cubic lattice.

PMID- 18338037
TI  - Closed-surface hexameric metal-organic nanocapsules derived from cavitand
      ligands.
AB  - Assembly of cavitand ligands, (4-), and Zn2+ ions yields a one-dimensional
      polymer comprised of hexameric, closed-surface, metal-organic nanocapsules.

PMID- 18338038
TI  - A soft coordination polymer derived from container molecule ligands.
AB  - Partial collapse of the ladder-shaped tunnels of a crystalline cryptophane
      derived coordination polymer is monitored by single crystal X-ray diffraction.

PMID- 18338039
TI  - Interpenetrated nano-capsule networks based on the alkali metal assisted assembly
      of p-carboxylatocalix[4]arene-O-methyl ether.
AB  - Reaction of p-carboxylatocalix[4]arene-O-methyl ether with either rubidium or
      caesium hydroxide results in the formation of interpenetrated nano-capsule
      networks with the calixarene in the 1,3-alternate conformation.

PMID- 18338040
TI  - Ultraselective fluorescent sensing of Hg2+ through metal coordination-induced
      molecular aggregation.
AB  - A new type of fluorescent sensor has been developed from a perylene based
      molecule, N,N'-dideoxythymidine-3,4,9,10-perylene-tetracarboxylic diimide (TT
      PTCDI); the strong, highly selective binding between the thymine ligand (T) and
      Hg2+ ion enables efficient sensing of mercury ions based on a fluorescence
      quenching mechanism, which is primarily caused by metal-coordination induced
      molecular aggregation.

PMID- 18338041
TI  - Palladium-catalysed cis- and trans-silaboration of terminal alkynes:
      complementary access to stereo-defined trisubstituted alkenes.
AB  - Palladium-catalysed cis- and trans-silaboration of terminal alkynes has been
      developed via the addition of (chlorodimethylsilyl)pinacolborane, followed by a
      one-pot conversion of the chloro group on the silicon atom to an isopropoxy
      group.

PMID- 18338042
TI  - The stereochemical course of bromoetherification of enynes.
AB  - Enynes undergo stereoselective syn intramolecular bromoetherification; the
      stereochemical course of the reaction was elucidated by X-ray crystallographic
      studies and by stereospecific synthesis of authentic bromoallenes.

PMID- 18338043
TI  - Catalytic alkene cyclohydroamination via an imido mechanism.
AB  - Chiral-at-metal half-sandwich diamide complexes catalyse enantioselective
      cyclohydroamination of aminoalkenes at unexpectedly high rates given their high
      coordination number and steric bulk; substantial evidence is presented which
      argues against the established sigma-bond insertion process and is strongly
      indicative of an imido [2+2] cycloaddition mechanism.

PMID- 18338044
TI  - Synthesis and dynamic structure of multinuclear Rh complexes of porphyrinoids.
AB  - Large porphyrinoids with three Rh(CO)2 groups at their dipyrrin units shows two
      step metal transposition through the macrocycle in solution and the equilibrium
      between the C3v-isomer and the Cs-isomer depends on the solvent polarity.

PMID- 18338045
TI  - Preparation of functional hybrid palladium nanoparticles using supercritical
      fluids: a novel approach to detach the growth and functionalization steps.
AB  - We report a novel and versatile approach to control separately the growth and
      functionalization steps in preparing functional nanomaterials. The applicability
      of this method was demonstrated with the preparation of palladium nanoparticles
      capped with thiol or stabilized with ionic liquid.

PMID- 18338046
TI  - Chiral amine-thioureas bearing multiple hydrogen bonding donors: highly efficient
      organocatalysts for asymmetric Michael addition of acetylacetone to nitroolefins.
AB  - New bifunctional organocatalysts amine-thioureas bearing multiple hydrogen
      bonding donors were synthesized and applied in catalytic asymmetric Michael
      addition of acetylacetone to aryl and alkyl nitroolefins. Multiple hydrogen
      bonding donors play a significant role in accelerating reactions, improving
      yields and enantioselectivities.

PMID- 18338047
TI  - Bio-inspired polyene cyclization: synthesis of tetracyclic terpenoids promoted by
      steroidal acetal-SnCl4.
AB  - This communication describes a highly efficient intermolecular polyene
      cyclization method using steroidal acetals as the initiators to synthesize
      tetracyclic terpenoids; both good yields and good asymmetric induction were
      obtained.

PMID- 18338048
TI  - Methylation of arenes via Ni-catalyzed aryl C-O/F activation.
AB  - Aryl C-O and C-F can be transformed into C-Me via Ni-catalyzed coupling with
      MeMgBr under mild conditions.

PMID- 18338049
TI  - One-step synthesis of polysubstituted benzene derivatives by multi-component
      cyclization of alpha-bromoacetate, malononitrile and aromatic aldehydes.
AB  - Polysubstituted benzene derivatives with an unprecedented substitution pattern
      are produced in a novel one-pot multi-component cyclization reaction from
      pyridine, ethyl alpha-bromoacetate, malononitrile and aromatic aldehyde in
      refluxing acetonitrile.

PMID- 18338050
TI  - Nucleotide insertion and bypass synthesis of pyrene- and BODIPY-modified
      oligonucleotides by DNA polymerases.
AB  - The chromophores pyrene and bordipyrromethenylbenzene directly linked to the 5
      position of uridine are tolerated and recognized as thymine derivatives by DNA
      polymerases in primer extension experiments.

PMID- 18338051
TI  - Dimerization of aromatic ureido pyrimidinedione derivatives: observation of an
      unexpected tautomer in the solid state.
AB  - Ureido pyrimidinedione derivatives with phenyl, 1-naphthyl and 2-naphthyl
      substituents form stable dimers via quadruple hydrogen bonding, but the 1
      naphthyl derivative presents an unexpected tautomer in the solid state.

PMID- 18338052
TI  - Giant vesicle formation through self-assembly of chitooligosaccharide-based graft
      copolymers.
AB  - A simple approach is described for the preparation of chitooligosaccharide-based
      giant vesicles with variable size by simply tuning the water content in the water
      dioxane mixture, by which reactive vesicles with diameters in the range of 0.5
      400 microm were easily prepared.

PMID- 18338053
TI  - Drastic enhancement of discotic mesomorphism induced by fluorination of the
      peripheral phenyl groups in triphenylene mesogens.
AB  - Four derivatives of hexakis(4-alkoxybenzoyloxy)triphenylene, for which peripheral
      phenylene groups are fluorinated at the inner and the outer positions were
      studied for their mesomorphic behaviour to reveal that the alteration of
      fluorinated positions in the phenyl rings leads to a drastic change of the
      mesomorphism involving the thermal stability.

PMID- 18338054
TI  - Poly(methyl methacrylate)s with pendant calixpyrroles: polymeric extractants for
      halide anion salts.
AB  - Poly(methyl methacrylate)s containing pendant octamethylcalix[4]pyrrole subunits
      were prepared and demonstrated to be capable of extracting tetrabutylammonium
      chloride and fluoride salts from aqueous media.

PMID- 18338055
TI  - Synthesis and microwave assisted polymerization of fluorinated 2-phenyl-2
      oxazolines: the fastest 2-oxazoline monomer to date.
AB  - The living cationic ring-opening polymerization of 2-oxazolines with fluorinated
      aromatic substituents was found to be strongly accelerated by o-fluoro
      substituents.

PMID- 18338056
TI  - Aptamer-based fluorescence sensor for rapid detection of potassium ions in urine.
AB  - We unveil a new homogeneous assay-using OliGreen and an ATP-binding aptamer-for
      the highly selective and sensitive detection of potassium ions.

PMID- 18338057
TI  - Direct C-H bond arylation of arenes with aryltin reagents catalysed by palladium
      complexes.
AB  - Direct C-H bond arylation of simple arenes with aryltin reagents has been
      successfully catalysed by PdCl2 in the presence of CuCl2. CuCl2 proved to be an
      activator for a palladium intermediate as well as an oxidant.

PMID- 18338059
TI  - WO3/CeO2-ZrO2, a promising catalyst for selective catalytic reduction (SCR) of
      NOx with NH3 in diesel exhaust.
AB  - A WO3/CeO2-ZrO2 catalyst system was discovered for selective catalytic reduction
      of NOx with NH3; the catalyst (10 wt% WO3 loading) showed nearly 100% NOx
      conversion in a temperature range of 200-500 degrees C, at a space velocity of 90
      000 h(-1) in a simulated diesel exhaust containing 550 ppm NOx (NO : NO2 feed
      ratio at 1.0), 10 vol% H2O and 10 vol% CO2; the catalyst also exhibited high
      temperature stability.

PMID- 18338058
TI  - Triarylpyridines: a versatile small molecule scaffold for G-quadruplex
      recognition.
AB  - The triarylpyridines are potent G-quadruplex ligands that are highly
      discriminating against duplex DNA and show promising selectivity between
      intramolecular quadruplexes.

PMID- 18338060
TI  - Cyclisation/fluorination of nitrogen containing dienes in superacid HF-SbF5: a
      new route to 3- and 4-fluoropiperidines.
AB  - Various N,N-diallylic amines and amides were rapidly converted to fluorinated
      piperidines after a novel cyclisation/fluorination reaction in superacid HF-SbF5.

PMID- 18338061
TI  - Hydrothermal synthesis and photoluminescent properties of stacked indium sulfide
      superstructures.
AB  - Unusual hierarchical stacked superstructures of cubic beta-In2S3 were fabricated
      via a facile hydrothermal process in the presence of a surfactant
      cetyltrimethylammonium bromide CTAB; the 3D superstructures were developed by
      helical propagation of surface steps from microflakes of 10-20 nm thickness.

PMID- 18338062
TI  - Comparison of solid particles, globular proteins and surfactants as emulsifiers.
AB  - The aim of this paper is to present a short overview of the main mechanisms
      operative in the formation and stabilization of emulsions by solid particles and,
      on this basis, to make comparisons between solid particles, surfactants and
      globular proteins as emulsifiers. When available, simple quantitative relations
      are presented, with the respective numerical estimates and discussion of the
      applicability of these relations to particle-stabilized systems. Non-obvious
      similarities between the different types of emulsifiers are outlined in several
      cases in which the description of the system can be performed at a
      phenomenological level. Examples are presented for the process of emulsification,
      where we show that several simple theoretical expressions, derived originally in
      the studies of surfactants and protein emulsifiers, can be successfully applied
      to particle-stabilized emulsions. In contrast, for the phenomena in which the
      detailed mechanisms of particle adsorption and film stabilization are important,
      the differences between the various emulsifiers prevail, thus making it
      impossible to use the same theoretical description. The most important specific
      characteristics of the solid particles which strongly affect their behavior are
      the high barrier to particle adsorption, high desorption energy and strong
      capillary forces between particles trapped in liquid films, which all originate
      in the relatively large particle size (as compared to the size of surfactant and
      protein molecules). The capillary mechanism of stabilization of liquid films by
      solid particles is reviewed in some detail, to emphasize its specific features
      and to demonstrate the applicability of several simple expressions for
      approximate estimates. Interestingly, we found that the hypothesis for some
      exceptionally high coalescence stability of the particle-stabilized emulsions is
      not supported by the experimental data available in literature. On the other
      hand, the particles are able to completely arrest the process of Ostwald ripening
      in foams and emulsions, and this effect can be easily explained with the high
      desorption energy of the particles and the resulting capillary effects.

PMID- 18338063
TI  - Chiral signatures in angle-resolved valence photoelectron spectroscopy of pure
      glycidol enantiomers.
AB  - Photoionization of the chiral molecule glycidol has been investigated in the
      valence region. Photoelectron circular dichroism (PECD) curves have been obtained
      at various photon energies by using circularly polarized VUV synchrotron
      radiation and a velocity map imaging technique to record angle-resolved
      photoelectron spectra (PES). The measured chiral asymmetries vary dramatically
      with the photon energy as well as with the ionized orbital, improving the
      effective orbital resolution of the PECD spectrum with respect to the PES.
      Typical asymmetry factors of 5% are observed, but the peak values measured range
      up to 15%. The experimental results are interpreted by continuum multiple
      scattering (CMS-Xalpha) calculations for several thermally accessible glycidol
      conformers. We find that a nearly quantitative agreement between theory and
      experiments can be achieved for the ionization of several molecular orbitals.
      Owing to the sensitivity of PECD to molecular conformation this allows us to
      identify the dominant conformer. The influence of intramolecular hydrogen bond
      orbital polarization is found to play a small yet significant role in determining
      the chiral asymmetry in the electron angular distributions.

PMID- 18338064
TI  - Adsorption of N2O on Cu(100): a combined scanning tunneling microscopy and
      density functional theory study.
AB  - The adsorption of N(2)O on Cu(100) has been studied by using scanning tunneling
      microscopy (STM). In the first molecular layer N(2)O forms a densely packed c(3 x
      2) structure, in which the molecules occupy two different adsorption sites. The
      bonding strength of this layer is found to be very weak as revealed by a low
      desorption temperature and the formation of misalignments and defects. Density
      functional theory (DFT) finds a stable c(3 x 2) structure in which the molecules
      are considerably bent due to charge transfer. In model calculations for a 2 x 2
      hollow phase we show that in order to reach the chemisorbed, bent configuration,
      the molecules have to pass an activation barrier. In the experimentally
      accessible range, this is apparently not possible and the molecules remain in a
      stable physisorbed state.

PMID- 18338065
TI  - Electronic spectroscopy of benzo[g,h,i]perylene and coronene inside helium
      nanodroplets.
AB  - We have recorded the electronic spectra of benzo[g,h,i]perylene and coronene and
      their van der Waals complexes with argon and oxygen with a helium-nanodroplet
      depletion spectrometer. These molecules differ by the addition of one and two
      fused benzene rings to perylene, which was previously studied in helium. The
      coronene spectrum is similar to a previously reported jet-cooled laser-induced
      fluorescence (LIF) spectrum. The van der Waals complexes with argon and oxygen
      show different complexation sites and maximum number of adsorbants. We report a
      vibronically resolved benzo[g,h,i]perylene S(1) <-- S(0) spectrum. The spectral
      lines are split in a similar way to that of several molecules studied before.
      However, surprisingly, while the van der Waals complexes with argon are free of
      the splitting, the complexes with oxygen retain the splitting, with increased
      linewidth and splitting. We could also observe the S(2) <-- S(0) origin
      transition of benzo[g,h,i]perylene which was previously observed by cavity ring
      down spectroscopy. While in general the two spectra are quite similar, the
      relative intensities and spectral shifts of several lines are different.

PMID- 18338066
TI  - Measurement and revised analysis of the torsional combination band of the
      nonpolar N2O dimer at 2249 cm(-1).
AB  - The high-resolution infrared spectrum of the weakly-bound dimer (N(2)O)(2) is
      studied using a rapid-scan tunable-diode laser spectrometer to probe a pulsed
      supersonic jet expansion. An observed band with c-type rotational structure is
      assigned as a combination of the intramolecular N(2)O nu(1) stretching vibration
      and the intermolecular out-of-plane dimer torsional vibration, with a vibrational
      origin at 2249.360 cm(-1). The resulting torsional frequency for the nonpolar
      N(2)O dimer is about 21.5 cm(-1). The present rotational analysis is completely
      different from that reported previously for the same band [Hecker et al., Phys.
      Chem. Chem. Phys., 2003, 5, 2333], which gave a band origin some 1.53 cm(-1)
      lower.

PMID- 18338067
TI  - Unravelling the ultrafast photodecomposition mechanism of dibenzoyl peroxide in
      solution by time-resolved IR spectroscopy.
AB  - The ultrafast photo-fragmentation of dibenzoyl peroxide (DBPO) is studied using
      femtosecond UV excitation at 266 nm and mid-infrared broadband probe pulses to
      elucidate the dissociation mechanism. With the help of (13)C-labeled DBPO it was
      possible to unambiguously assign transient IR bands in the fingerprint region to
      the benzoyloxy radical. Our experiments show that the fragmentation is controlled
      by the S(1)-lifetime of DBPO and within 0.4 +/- 0.2 ps leads to a
      benzoyloxy/phenyl radical pair plus CO(2)via concerted bond breakage of the O-O
      and the phenyl-C(carbonyl) bond. 20% of the radical pairs geminately recombine to
      phenyl benzoate on a timescale of 70 ps.

PMID- 18338068
TI  - A first-principles study of K adsorption on Pb(111).
AB  - Ab initio total-energy density functional theory calculations with supercell
      models have been employed to investigate the R30 degrees and (2 x 2) structures
      of K on the Pb(111) surface. Four "on-surface" sites and a substitutional site
      were considered. The calculations showed that the substitutional site is more
      stable than all the on-surface sites, due to its low vacancy formation energy.
      The calculated R30 degrees geometry agrees well with the LEED results. The
      density-of-states analysis indicates that the K atom loses part of its loosely
      bound valence s electron. From the electron density distributions, it was found
      that the lowering of the work function after the substitutional adsorption can be
      attributed to the dipole moment, associated with the positively polarized
      adsorbate atom that is characterized by charge depletion from the K vacuum sides
      and charge accumulation in the region between K and Pb atoms. Our results
      indicate that the bonding of K with the Pb(111) surface has a mixed ionic and
      metallic bond character.

PMID- 18338069
TI  - The dynamics of reaction of Cl atoms with tetramethylsilane.
AB  - Rotational state distributions and state-selected CM-frame angular distributions
      were measured for HCl (v' = 0, j') products from the reaction of Cl-atoms with
      tetramethylsilane (TMS) under single collision conditions at a collision energy,
      E(coll), of 8.2 +/- 2.0 kcal mol(-1). The internal excitation of these products
      was very low with only 2% of the total energy available partitioned into HCl
      rotation. A transition state with a quasi-linear C-H-Cl moiety structure was
      computed and used to explain this finding. A backward peaking differential cross
      section was also reported together with a product translational energy (T')
      distribution with a maximum at T' approximately E(coll). This scattering
      behaviour is accounted for by reactions proceeding through a tight transition
      state on a highly skewed potential energy surface, which favours collisions at
      low impact parameters with a strong kinematic constraint on the internal
      excitation of the products. The large Arrhenius pre-exponential factor previously
      reported for this reaction is reconciled with the tight differential scattering
      observed in our study by considering the large size of the TMS molecule.

PMID- 18338070
TI  - An alternative NMR method to determine nuclear shielding anisotropies for
      molecules in liquid-crystalline solutions with (13)C shielding anisotropy of
      methyl iodide as an example.
AB  - An alternative NMR method for determining nuclear shielding anisotropies in
      molecules is proposed. The method is quite simple, linear and particularly
      applicable for heteronuclear spin systems. In the technique, molecules of
      interest are dissolved in a thermotropic liquid crystal (LC) which is confined in
      a mesoporous material, such as controlled pore glass (CPG) used in this study.
      CPG materials consist of roughly spherical particles with a randomly oriented and
      connected pore network inside. LC Merck Phase 4 was confined in the pores of
      average diameter from 81 to 375 A and LC Merck ZLI 1115 in the pores of average
      diameter 81 A. In order to demonstrate the functionality of the method, the (13)C
      shielding anisotropy of (13)C-enriched methyl iodide, (13)CH(3)I, was determined
      as a function of temperature using one dimensional (13)C NMR spectroscopy.
      Methane gas, (13)CH(4), was used as an internal chemical shift reference. It
      appeared that methyl iodide molecules experience on average an isotropic
      environment in LCs inside the smallest pores within the whole temperature range
      studied, ranging from bulk solid to isotropic phase. In contrast, in the spaces
      in between the particles, whose diameter is approximately 150 microm, LCs behave
      as in the bulk. Consequently, isotropic values of the shielding tensor can be
      determined from spectra arising from molecules inside the pores at exactly the
      same temperature as the anisotropic ones from molecules outside the pores. Thus,
      for the first time in the solution state, shielding anisotropies can easily be
      determined as a function of temperature. The effects of pore size as well as of
      different LC media on the shielding anisotropy are examined and discussed.

PMID- 18338071
TI  - Analysis of temperature programmed desorption (TPD) data for the characterisation
      of catalysts containing a distribution of adsorption sites.
AB  - This paper discusses some methods of analysing TPD data for samples obeying first
      order desorption kinetics and proposes several improvements to existing practice.
      The methods apply in the case when the Arrhenius parameters A and E for each site
      are independent of coverage, and thus are normally suitable for the
      characterisation of porous solids. An improved implementation of the condensation
      approximation method is proposed to gain an initial estimate of the adsorption
      site distribution. Further, a variation of the method is proposed that can be
      used when A is a function of E. The initial estimate of the distribution can be
      used to analyse data obtained by an interrupted TPD experiment, in which heating
      is halted at a specified temperature. This method provides a reliable method of
      determining the parameter A for a peak in the distribution. Finally,
      regularisation procedures for obtaining physically sensible distributions from
      "noisy" TPD data are discussed. It is shown that a penalty function based on the
      square of the second derivative of the distribution is normally most suitable for
      analysing TPD data, at least in the case when the L-curve method is used to
      select the regularisation parameter.

PMID- 18338072
TI  - Adsorption of polyelectrolytes from semi-dilute solutions on an oppositely
      charged surface.
AB  - We propose a detailed description of the structure of the layer formed by
      polyelectrolyte chains adsorbed onto an oppositely charged surface in the semi
      dilute regime. We combine the mean-field Poisson-Boltzmann-Edwards theory and the
      scaling functional theory to describe the variations of the monomer
      concentration, the electrostatic potential, and the local grafting density with
      the distance to the surface. For long polymers, we find that the effective charge
      of the decorated surface (surface plus adsorbed polyelectrolytes) can be much
      larger than the bare charge of the surface at low salt concentration, thus
      providing an experimental route to a "supercharging" type of effect.

PMID- 18338073
TI  - TNFalpha in the pathogenesis of diabetes-induced embryopathies: functions and
      targets.
AB  - Hyperglycemia-induced increase in the production of reactive oxygen species (ROS)
      is proposed to be an initial step in the pathogenesis of diabetes-induced
      spontaneous abortions and structural inborn anomalies. However, the subsequent
      steps in this process are incompletely understood. One of the key molecules
      involved is tumor necrosis factor-alpha (TNFalpha): its expression is regulated
      by ROS and it regulates ROS production in turn. This cytokine has been the focus
      of many studies addressing the mechanisms of different forms of diabetes-induced
      embryopathies, such as early pregnancy loss, inborn anomalies, fetal growth
      retardation as well as some pathologies appearing during adult life. In this
      review, we analyze the results of these studies and discuss how TNFalpha may
      regulate the response of pre- and post-implantation stage embryos to diabetes
      induced detrimental stimuli. The data presented in this review suggest that
      TNFalpha may play a dual role in the pathogenesis of diabetes-induced
      embryopathies. It may act both as a mediator of diabetes-induced embryotoxic
      stimuli leading to the death of peri-implantation stage embryos and, possibly, as
      a suppressor of diabetes-induced apoptosis in post-implantation stage embryos. It
      also appears that TNFalpha fulfills these functions via interaction with leukemia
      inhibitory factor (LIF) and the transcription factor NF-kappaB. These molecules
      are presently considered as attractive targets for the treatment of diabetes
      induced complications. Therefore, further studies addressing their role in the
      mechanisms underlying diabetes-induced embryopathies are needed to evaluate the
      safety of such therapies for diabetic women of childbearing age.

PMID- 18338075
TI  - Effectiveness of an intensive nutritional intervention in patients with type 2
      diabetes mellitus: results from a pilot study.
AB  - The aim of this pilot study was to compare the effects of an intensive
      nutritional intervention with usual care conditions on dropout rate, body weight,
      lifestyle changes and glycemic control in patients with type 2 diabetes mellitus
      (T2DM). Thirty outpatients with T2DM but without insulin treatment (mean age: 57
      +/- 9 yr) were randomly assigned to one of the two intervention groups: intensive
      care (IC) or usual care (UC). Patients in the UC group were given advice about
      dietary and physical activity goals in one consultation session at baseline,
      while patients in the IC group attended five goal-oriented consultation sessions
      held approximately every two weeks from baseline onwards. Changes in body weight,
      T2DM knowledge, dietary intake, physical activity, HbA1c, and percentage of
      dropouts were evaluated at 1-year follow-up post-intervention. Fifty percent of
      patients quitted the program and were classified as "dropouts". Program
      completers were older and included a lower percentage of newly diagnosed T2DM
      compared with dropouts. A tendency to a negative association between attendance
      of the IC group and the likelihood of dropping out was found (p = 0.08). No
      difference was detected between UC and IC groups regarding changes in body
      weight, HbA1c or other outcome measures, at post-intervention or 1-year follow
      up. This pilot study did not confirm advantages of intensive nutritional
      intervention in T2DM patients in terms of glycemic control, body weight, diet and
      physical activity. However, the high dropout rate may have hampered its
      effectiveness.

PMID- 18338074
TI  - Pleiotropic Roles of PDX-1 in the Pancreas.
AB  - It is well known that pancreatic and duodenal homeobox factor-1 (PDX-1) plays a
      pleiotropic role in the pancreas. In the developing pancreas, PDX-1 is involved
      in both pancreas formation and beta-cell differentiation. In mature beta-cells,
      PDX-1 transactivates insulin and other beta-cell-related genes such as GLUT2 and
      glucokinase. Furthermore, PDX-1 plays an important role in the induction of
      insulin-producing cells in various non-beta-cells and is thereby a possible
      therapeutic target for diabetes. On the other hand, under diabetic conditions,
      expression and/or activity of PDX-1 in beta-cells is reduced, which leads to
      suppression of insulin biosynthesis and secretion. It is likely that PDX-1
      inactivation explains, at least in part, the molecular mechanism for beta-cell
      glucose toxicity found in diabetes.

PMID- 18338076
TI  - Evaluation of Apolipoprotein M Serum Concentration as a Biomarker of HNF-1alpha
      MODY.
AB  - Apolipoprotein M (apoM) is a 26-kDa protein expressed mainly in the liver and
      kidneys. It is present predominantly in high-density lipoproteins (HDL). ApoM
      expression is influenced by the hepatocyte nuclear factor-1alpha (HNF-1alpha),
      which is a transcription factor associated with the pathogenesis of MODY. Some
      earlier data suggested that apoM levels were lower in the serum of HNF-1alpha
      MODY subjects, than in that of other diabetics and healthy controls. The aim of
      this study was to evaluate apoM as a biomarker for HNF-1alpha MODY. We included
      in this study 48 HNF-1alpha mutation carriers (40 diabetic patients and 8
      subjects with normal glucose levels in the fasted state) from the Polish
      Nationwide Registry of MODY. In addition, we examined 55 T2DM patients and 55
      apparently healthy volunteers who had normal fasting glucose levels. ApoM was
      measured by the sandwich dot-blot technique with recombinant apoM (Abnova) as a
      protein standard, mouse anti-human apoM monoclonal primary antibody and rat anti
      mouse HRP-conjugated secondary antibody (BD Biosciences). Mean apoM level in the
      MODY group was 13.6 mug/ml, SD 1.9 (13.5 mug/ml, SD 1.7 in diabetic subjects and
      13.9 mug/ml, SD 2.0 in non-diabetic mutation carriers respectively). In the T2DM
      group, mean apoM level was 13.7 mug/ml, SD 2.1, while it reached 13.8 mug/ml, SD
      2.0 in healthy controls. There was no difference between apoM serum
      concentrations in all the study groups. In summary, our study showed no
      association between HNF-1alpha mutations resulting in MODY phenotype and apoM
      levels. Thus, we cannot confirm the clinical usefulness of apoM as a biomarker of
      HNF-1alpha MODY.

PMID- 18338077
TI  - First-degree relatives of patients with type 2 diabetes mellitus and risk of non
      alcoholic Fatty liver disease.
AB  - AIMS: The aim of this study was to determine whether first-degree relatives (FDR)
      of patients with type 2 diabetes mellitus (T2DM) are at higher risk of non
      alcoholic fatty liver disease (NAFLD) than healthy controls. METHODS: A total of
      222 FDR of consecutive patients with T2DM aged between 35 and 55 years and 202
      healthy individuals with no family history of diabetes were investigated for
      NAFLD. Fatty liver was diagnosed by ultrasonography using standard criteria.
      Height, weight, fasting glucose, alanine aminotransferase (ALT), total
      cholesterol and triglyceride were determined by routine laboratory methods.
      RESULTS: Compared to subjects with no family history of diabetes, the age and sex
      adjusted odds ratio (OR) of NAFLD was 1.83 (95% CI: 1.11-3.03) for FDR of
      patients with T2DM. After further adjusting for BMI, fasting glucose, ALT,
      asparate aminotransferase (AST), triglyceride and cholesterol, the multivariate
      OR of prevalent NAFLD in FDR of patients with T2DM compared with individuals with
      no family history of diabetes was 1.56 (95% CI: 0.85-2.86). CONCLUSIONS: The
      present study suggests that the relation between FDR of patients with T2DM and
      NAFLD is affected by the other covariates, in particular obesity, which points to
      a more complex relationship between the diseases. It appears that obesity and
      diabetes may independently predispose to NAFLD.

PMID- 18338078
TI  - The incidence of microalbuminuria and its associated risk factors in type 2
      diabetic patients in isfahan, iran.
AB  - AIM: The study was carried out to determine the five-year incidence of
      microalbuminuria and to assess its associated risk factors for type 2 diabetic
      patients in Isfahan, Iran. METHODS: 505 type 2 diabetic patients (22% male, 78%
      female) with normal urinary albumin levels, being treated at Isfahan Endocrine
      and Metabolism Research Center, were consecutively selected. After the initial
      selection in 1999, the patients were followed for five years. Mean and standard
      deviation (SD) of age and duration of diabetes was 57.4 (9.5) and 10.2 (4.7)
      years, respectively. BMI, blood pressure, fasting plasma glucose, HbA1c, serum
      lipids and serum creatinine were measured and re-examined every three months. 24
      h urinary albumin excretion was measured and reviewed annually. Microalbuminuria
      was diagnosed when at least two measurements indicated the excretion of more than
      30 mg albumin in 24-h urinary samples. RESULTS: During 5-year follow up, 176
      patients developed microalbuminuria, giving an incidence rate of 82.3/1000
      person/year (95% CI: 78.3-86.2). Males had a higher incidence than females (104.4
      vs. 66.2/1000 person/year, p < 0.001). Duration of diabetes, abnormal levels of
      HbA1c, hypertension and high serum creatinine were significantly associated with
      microalbuminuria. There was no difference in mean of age, BMI, and lipid levels
      between patients with and without microalbuminuria. Multivariate analysis was
      used to show that duration of diabetes, HbA1c, hypertension and retinopathy were
      the independent variables related to microalbuminuria. CONCLUSIONS: The incidence
      of microalbuminuria in the study population was higher than in other populations.
      The higher incidence and the considerable gender difference in this population
      may be attributed to inferior glycemic control and lack in screening for risk
      factors, but this needs to be explored in further studies.

PMID- 18338079
TI  - EJBI and methods agree on close cooperation.

PMID- 18338080
TI  - Estimating morbidity rates from electronic medical records in general practice.
      Evaluation of a grouping system.
AB  - OBJECTIVES: In this study, we evaluated the internal validity of EPICON, an
      application for grouping ICPC-coded diagnoses from electronic medical records
      into episodes of care. These episodes are used to estimate morbidity rates in
      general practice. METHODS: Morbidity rates based on EPICON were compared to a
      gold standard; i.e. the rates from the second Dutch National Survey of General
      Practice. We calculated the deviation from the gold standard for 677 prevalence
      and 681 incidence rates, based on the full dataset. Additionally, we examined the
      effect of case-based reasoning within EPICON using a comparison to a simple, not
      case-based method (EPI-0). Finally, we used a split sample procedure to evaluate
      the performance of EPICON. RESULTS: Morbidity rates that are based on EPICON
      deviate only slightly from the gold standard and show no systematic bias. The
      effect of case-based reasoning within EPICON is evident. The addition of case
      based reasoning to the grouping system reduced both systematic and random error.
      Although the morbidity rates that are based on the split sample procedure show no
      systematic bias, they do deviate more from the gold standard than morbidity rates
      for the full dataset. CONCLUSIONS: Results from this study indicate that the
      internal validity of EPICON is adequate. Assuming that the standard is gold,
      EPICON provides valid outcomes for this study population. EPICON seems useful for
      registries in general practice for the purpose of estimating morbidity rates.

PMID- 18338081
TI  - Modeling repeated time-to-event health conditions with discontinuous risk
      intervals. An example of a longitudinal study of functional disability among
      older persons.
AB  - OBJECTIVES: Researchers have often used rather simple approaches to analyze
      repeated time-to-event health conditions that either examine time to the first
      event or treat multiple events as independent. More sophisticated models have
      been developed, although previous applications have focused largely on such
      outcomes having continuous risk intervals. Limitations of applying these models
      include their difficulty in implementation without careful attention to forming
      the data structures. METHODS: We first review time-to-event models for repeated
      events that are extensions of the Cox model and frailty models. Next, we develop
      a way to efficiently set up the data structures with discontinuous risk intervals
      for such models, which are more appropriate for many applications than the
      continuous alternatives. Finally, we apply these models to a real dataset to
      investigate the effect of gender on functional disability in a cohort of older
      persons. For comparison, we demonstrate modeling time to the first event.
      RESULTS: The GEE Poisson, the Cox counting process, and the frailty models
      provided similar parameter estimates of gender effect on functional disability,
      that is, women had increased risk of bathing disability and other disability
      (disability in walking, dressing, or transferring) as compared to men. These
      results, especially for other disabilities, were quite different from those
      provided by an analysis of the first-event outcomes. However, the effect of
      gender was no longer significant in the counting process model fully adjusted for
      covariates. CONCLUSION: Modeling time to only the first event may not be
      adequate. After properly setting up the data structures, repeated event models
      that account for the correlation between multiple events within subjects can be
      easily implemented with common statistical software packages.

PMID- 18338082
TI  - Austria's path toward nationwide electronic health records.
AB  - OBJECTIVES: This article discusses current planning activities in Austria after
      legislation has been passed to introduce the electronic health record (EHR).
      METHODS: After describing similar activities in several other countries, the
      authors explore the current situation of healthcare telematics and imminent steps
      toward the implementation of a lifelong EHR. RESULTS: Substantial efforts have
      been made to coordinate healthcare telematics in Austria since the mid-1990s. One
      result of these efforts was the definition of a framework for electronic data
      exchange. A number of standardization projects were also implemented. Major steps
      have been taken as part of an ongoing healthcare reform to promote the use of
      healthcare telematics. One important example is a national initiative whose
      objective is to implement the EHR. This initiative is extensively discussed along
      with other national activities related to healthcare telematics. CONCLUSION: This
      EHR initiative has prepared the ground for extensive planning that is currently
      under way to implement a lifelong EHR in Austria on a national level. Introducing
      the EHR will have a strong impact on Austrian healthcare and should be performed
      in concert with international activities. The authors offer a number of practical
      recommendations for the implementation of an EHR on a national level.

PMID- 18338083
TI  - A comparison of websites from Spanish, American and British hospitals.
AB  - OBJECTIVE: To evaluate and compare the user-orientation of Spanish, American and
      British hospital websites. METHODS: A descriptive study of 32 hospital portals
      (12 Spanish, 10 American and 10 British) was carried out in which the following
      were analyzed: website readability according to the Flesch Index, websites
      accessibility using the Web Accessibility Test, and the quality of information
      provided using the "e-Information Scale of Health Care Centers". RESULTS: Fifty
      percent of the user-oriented information quality attributes are met. Readability
      indices tend to be below 60 (standard readability), and only 10 of the 32
      websites meet the accessibility criteria. CONCLUSIONS: Most portals exhibit
      accessibility problems that favor computer illiteracy. There is a wide
      variability in terms of website readability and in terms of user-oriented
      content.

PMID- 18338084
TI  - A finite element formulation for atrial tissue monolayer.
AB  - OBJECTIVES: Using computer models for the study of complex atrial arrhythmias
      such as atrial fibrillation is computationally demanding as long observation
      periods in the order of tens of seconds are required. A well established approach
      for reducing computational workload is to approximate the thin atrial walls by
      curved monolayers. On the other hand, the finite element method (FEM) is a well
      established approach to solve the underlying partial differential equations.
      METHODS: A generalized 2D finite element method (FEM) is presented which computes
      the corresponding stiffness and coupling matrix for arbitrarily shaped monolayers
      (ML). Compared to standard 2D FEM, only one additional coordinate transformation
      is required. This allows the use of existing FEM software with minor
      modifications. The algorithm was tested to simulate wave propagation in benchmark
      geometries and in a model of atrial anatomy. RESULTS: The ML model was able to
      simulate electric activation in curved tissue with anisotropic conductivity.
      Simulations in branching tissue yielded slightly different patterns when compared
      to a volumetric model with finite thickness. In the model of atrial anatomy the
      computed activation times for five different pacing protocols displayed a
      correlation of 0.88 compared to clinical data. CONCLUSIONS: The presented method
      provides a useful and easily implemented approach to model wave propagation in
      MLs with a few restrictions to volumetric models.

PMID- 18338085
TI  - DMSP--Database for Modeling Signaling Pathways. Combining biological and
      mathematical modeling knowledge for pathways.
AB  - OBJECTIVES: Presently, the protein interaction information concerning different
      signaling pathways is available in a qualitative manner in different online
      protein interaction databases. The challenge here is to derive a quantitative way
      of modeling signaling pathways from qualitative way of modeling signaling
      pathways from a qualitative level. To address this issue we developed a database
      that includes mathematical modeling knowledge and biological knowledge about
      different signaling pathways. METHODS: The database is part of an integrative
      environment that includes environments for pathway design, visualization,
      simulation and a knowledge base that combines biological and modeling information
      concerning pathways. The system is designed as a client-server architecture. It
      contains a pathway designing environment and a simulation environment as upper
      layers with a relational knowledge base as the underlying layer. RESULTS: DMSP-
      Database for Modeling Signaling Pathways incorporates biological datasets from
      online databases like BIND, DIP, PIP, and SPiD. The modeling knowledge that has
      been incorporated is based on a literature study. Pathway models can be designed,
      visualized and simulated based on the knowledge stored in the DMSP. The user can
      download the whole dataset and build pathway models using the knowledge stored in
      our database. As an example, the TNFalpha pathway model was implemented and
      tested using this approach. CONCLUSION: DMSP is an initial step towards the aim
      of combining modeling and biological knowledge concerning signaling pathways. It
      helps in understanding pathways in a qualitative manner from a qualitative level.
      Simulation results enable the interpretation of a biological system from a
      quantitative and system-theoretic point of view.

PMID- 18338086
TI  - User acceptance of a picture archiving and communication system. Applying the
      unified theory of acceptance and use of technology in a radiological setting.
AB  - OBJECTIVE: The aim of this study is to gain insight into the individual user
      acceptance of PACS by the radiology department staff of the Ghent University
      Hospital. Hereto a basic--direct effects only--form of UTAUT was assessed.
      METHODS: Ninety-four questionnaires were distributed and 56 usable questionnaires
      were returned (19 radiologists - 37 technologists). The questionnaire consisted
      of scales of Venkatesh et al. [13] for performance expectancy (PE), effort
      expectancy (EE), facilitating conditions (FC), social influence (SI), self
      efficacy (SE), attitude (ATT), anxiety (ANX) and behavioral intention (BI), and a
      scale of Moore et al. [22] to assess the perceived voluntariness of PACS-use.
      RESULTS: The reliability of all scales, except FC and voluntariness, was
      acceptable to good. The voluntariness scale was divided into a mandatoriness
      (MAN) and a voluntariness (VOL) measure. Both radiologists and technologists seem
      to welcome PACS, with radiologists having higher ratings on PE, EE, ATT, VOL and
      BI. Only PE and FC were salient for predicting BI, while EE and SI were not
      salient. Variance explained in behavioral intention to use PACS was 48%.
      CONCLUSION: Both radiologists and technologists were positive towards PACS and
      had strong intentions to use PACS. As other healthcare professionals, they appear
      to make their technology acceptance decision independent from their superiors,
      hereby focusing on usefulness rather than on ease of use. It is also important
      that support is supplied. Basic UTAUT is an adequate model to assess technology
      acceptance in a radiological setting.

PMID- 18338087
TI  - Development of a telediagnosis endoscopy system over secure internet.
AB  - OBJECTIVES: We developed a new telediagnosis system to securely transmit high
      quality endoscopic moving images over the Internet in real time. This system
      would enable collaboration between physicians seeking advice from endoscopists
      separated by long distances, to facilitate diagnosis. METHODS: We adapted a new
      type of digital video streaming system (DVTS) to our teleendoscopic diagnosis
      system. To investigate its feasibility, we conducted a two-step experiment. A
      basic experiment was first conducted to transmit endoscopic video images between
      hospitals using a plain DVTS. After investigating the practical usability, we
      incorporated a secure and reliable communication function into the system, by
      equipping DVTS with "TCP2", a new security technology that establishes secure
      communication in the transport layer. The second experiment involved
      international transmission of teleendoscopic image between Hawaii and Japan using
      the improved system. RESULTS: In both the experiments, no serious transmission
      delay was observed to disturb physicians' communications and, after subjective
      evaluation by endoscopists, the diagnostic qualities of the images were found to
      be adequate. Moreover, the second experiment showed that "TCP2-equipped DVTS"
      successfully executed high-quality secure image transmission over a long distance
      network. CONCLUSIONS: We conclude that DVTS technology would be promising for
      teleendoscopic diagnosis. It was also shown that a high quality, secure
      teleendoscopic diagnosis system can be developed by equipping DVTS with TCP2.

PMID- 18338088
TI  - Double-smoothing in kernel hazard rate estimation.
AB  - OBJECTIVES: In oncological studies, the hazard rate can be used to differentiate
      subgroups of the study population according to their patterns of survival risk
      over time. Nonparametric curve estimation has been suggested as an exploratory
      means of revealing such patterns. The decision about the type of smoothing
      parameter is critical for performance in practice. In this paper, we study data
      adaptive smoothing. METHODS: A decade ago, the nearest-neighbor bandwidth was
      introduced for censored data in survival analysis. It is specified by one
      parameter, namely the number of nearest neighbors. Bandwidth selection in this
      setting has rarely been investigated, although the heuristical advantages over
      the frequently-studied fixed bandwidth are quite obvious. The asymptotical
      relationship between the fixed and the nearest-neighbor bandwidth can be used to
      generate novel approaches. RESULTS: We develop a new selection algorithm termed
      double-smoothing for the nearest-neighbor bandwidth in hazard rate estimation.
      Our approach uses a finite sample approximation of the asymptotical relationship
      between the fixed and nearest-neighbor bandwidth. By so doing, we identify the
      nearest-neighbor bandwidth as an additional smoothing step and achieve further
      data-adaption after fixed bandwidth smoothing. We illustrate the application of
      the new algorithm in a clinical study and compare the outcome to the traditional
      fixed bandwidth result, thus demonstrating the practical performance of the
      technique. CONCLUSION: The double-smoothing approach enlarges the methodological
      repertoire for selecting smoothing parameters in nonparametric hazard rate
      estimation. The slight increase in computational effort is rewarded with a
      substantial amount of estimation stability, thus demonstrating the benefit of the
      technique for biostatistical applications.

PMID- 18338089
TI  - Mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome): assessment of joint
      mobility and grip and pinch strength.
AB  - OBJECTIVE: To describe the profile of joint mobility and grip and pinch strength
      of MPS VI patients and to correlate this with urinary excretion of
      glycosaminoglycans (GAGs), ARSB activity, and the distance covered in a 6-minute
      walking test (6MWT). METHODS: This was an observational study of 28 patients with
      MPS VI, who had not undergone specific treatment. All patients were assessed for
      amplitude of joint mobility (shoulder, elbow, and knee), grip and pinch strength
      and urinary GAG excretion and also performed the 6MWT. RESULTS: Shoulder flexion
      exhibited the greatest limitation, with no correlation with age, followed by knee
      extension and elbow flexion, both of which were correlated inversely with age.
      Hand grip strength was compromised in all patients, and pinch strength exhibited
      a positive correlation with age. CONCLUSIONS: The fact that restricted shoulder
      flexion was not correlated with age suggests that this finding is present early
      on in MPS VI and that it constitutes an important clinical sign that should
      arouse diagnostic suspicion of this disease. The amplitude of knee extension and
      elbow flexion, in turn, are possible markers of disease progression since they
      have a negative correlation with age. Further studies are needed to confirm these
      hypotheses.

PMID- 18338090
TI  - Co-morbidities in people with COPD: a result of multiple diseases, or multiple
      manifestations of smoking and reactive inflammation?
AB  - There has been increased awareness and recognition of COPD in both developed and
      developing nations. As people with COPD are identified and treated before they
      reach end-stage lung disease, the multiple morbidities associated with COPD have
      been recognised. These morbidities affect many areas of the body and currently
      are often treated with numerous different drugs. This poly-pharmacy, and the need
      for therapy by multiple organ-specific specialists, is not optimal and often not
      feasible for patients with COPD. New information on many of the common multiple
      morbidities suggests that it may be possible to explain--and in the future
      control or treat--these multiple morbidities, by addressing one common trigger
      and a common final pathway of inflammation. This review outlines some of the
      reasons why it is time to consider a 'whole body' approach to COPD, rather than
      clinicians continuing to address the lungs first and then each additional organ
      one at a time.

PMID- 18338091
TI  - Alcohol-based pressurised metered-dose inhalers for use in asthma: a descriptive
      study.
AB  - BACKGROUND: Chlorofluorocarbons (CFCs) have historically served as the
      propellants of choice in pressurised metered-dose asthma inhalers, but concern
      has been raised in recent decades regarding their damaging effect on the ozone
      layer. Among the alternative propellants being considered is alcohol, which can
      be used as a co-solvent in asthma inhalers. Healthcare professionals need to be
      aware of alcohol-containing inhalers, since certain populations may have
      religious and/or cultural concerns regarding the use of such preparations.
      OBJECTIVES: To identify pressurised metered-dose asthma inhalers which contain
      alcohol-based propellants. METHODS: We searched the British National Formulary to
      identify companies that manufacture asthma treatments and wrote to them to
      enquire about which of their products contained alcohol and if so in what
      percentage. These direct contacts were supplemented by searching medical
      databases and the Internet for additional information. RESULTS: We identified 11
      manufacturers of asthma inhalers, seven of which produced pressurised metered
      dose inhalers; of these, six were willing to disclose the requested information,
      and information on the seventh product was obtained from an alternative valid
      source of information. Most CFC preparations contain alcohol, but CFC- and
      alcohol-free preparations do exist. CONCLUSIONS: Clinicians need to be aware that
      the majority of CFC-free inhalers contain alcohol. Alcohol-free, and CFC- and
      alcohol-free, preparations are available for the delivery of both rescue and
      preventative treatment and these should be considered for use in those patients
      who may have concern about alcohol-based treatments.

PMID- 18338092
TI  - [Activities report of the Central Ethics Commission on Stem Cell Research (ZES):
      Fifth Report after taking effect of the Stem Cell Law (StZG) for the time period
      from 12/1/2006 to 11/30/2007].

PMID- 18338093
TI  - Risk factors associated with anal sphincter tear difference among midwife,
      private obstetrician, and resident deliveries.
AB  - To identify risk factors that account for the difference in anal sphincter tear
      (AST) among midwife, private obstetrician, and resident deliveries. We performed
      a retrospective review of our obstetrical database and used logistic regression
      analysis to identify risk factors for AST. The relationship between delivery
      technique and AST was evaluated by comparing AST increase between vaginal
      deliveries without and with an episiotomy among the three categories of
      providers. After adjusting for risk factors, private obstetricians (OR: 1.81, 95%
      CI: 1.27-2.56) and residents (OR: 1.60, 95% CI: 1.20-2.15) had a higher rate of
      AST during vaginal delivery than midwives. Episiotomy increased the odds of AST
      by four-fold for midwives, two-fold for private obstetricians, and eight-fold for
      residents. Although midwife and resident's delivery methods were associated with
      more AST, neither experienced this complication more frequently than private
      obstetricians. This suggests that midwives and residents probably misdiagnosed
      some AST.

PMID- 18338094
TI  - Long-term follow-up of intravaginal slingplasty operation for urinary stress
      incontinence.
AB  - The objective of this study was to evaluate the long-term complications of the
      intravaginal slingplasty (IVS) operation for stress urinary incontinence in women
      operated 5 years ago. Out of 25 operated patients, seven patients experienced
      erosion up to 5 years after the primary operations. In six patients, parts of the
      tape had to be removed several times. Two patients developed a suprapubic
      abscess. We recommend that the IVS tape is abandoned.

PMID- 18338095
TI  - A combined intravesical therapy with hyaluronic acid and chondroitin for
      refractory painful bladder syndrome/interstitial cystitis.
AB  - The aims of this study were to evaluate the efficacy and tolerability of
      intravesical instillations of high-molecular-weight hyaluronic acid (HA) 1.6% and
      chondroitin sulfate (CS) 2.0% in patients with refractory painful bladder
      syndrome/interstitial cystitis (PBS/IC) and to observe their impact on Quality of
      Life. Twenty-three women were enrolled. They received bladder instillations with
      HA and CS weekly for 20 weeks and then monthly for 3 months. Mean follow-up after
      completion of therapy was 5 months. We observed a significant improvement in
      urinary symptoms on voiding diaries and Visual Analogue Scale for frequency (p =
      0.045), urgency (p = 0.005), and pain (p = 0.001). The O'Leary-Sant Interstitial
      Cystitis Symptom Index and Interstitial Cystitis Problem Index resulted in a
      significant improvement in both scores (p = 0.004 and 0.01, respectively). The
      Pelvic Pain and Urgency/Frequency Symptom Scale only showed significant
      improvement in the symptom score (p = 0.001). This promising experience seems to
      offer an additional therapeutic option in patients with refractory PBS/IC.

PMID- 18338096
TI  - Comparison of sex steroid measurements in men by immunoassay versus mass
      spectroscopy and relationships with cortical and trabecular volumetric bone
      mineral density.
AB  - In men, measurement of serum testosterone and estradiol levels with immunoassays
      correlated with mass spectroscopic measurements, and correlations of sex steroids
      with volumetric bone mineral density were similar. INTRODUCTION: While
      immunoassays have been used extensively for measurement of serum testosterone (T)
      and estradiol (E(2)) levels, there is concern about their specificity,
      particularly at low E(2) levels as present in men. METHODS: We compared T and
      E(2) measured by mass spectroscopy to levels measured by immunoassay in men (n =
      313, age 22 to 91 years) and related these to volumetric bone mineral density
      (vBMD) at various skeletal sites. RESULTS: Serum T and non-SHBG bound (or
      bioavailable) T levels by immunoassay correlated well with the corresponding mass
      spectroscopy measurements (R = 0.90 and 0.95, respectively, P < 0.001); the
      correlations for serum E(2) measured using the two techniques were less robust (R
      = 0.63 for total E(2) and 0.84 for bioavailable E(2), P < 0.001). Overall
      relationships between serum bioavailable T and E(2) levels with vBMD at various
      skeletal sites were similar for the immunoassay and mass spectroscopic measures.
      CONCLUSIONS: Although E(2) levels with immunoassay correlate less well with the
      mass spectroscopic measurements than do the T measurements in men, our findings
      indicate that the fundamental relationships observed previously between vBMD and
      the sex steroids by immunoassay are also present with the mass spectroscopic
      measurements.

PMID- 18338097
TI  - Regulatory pathways revealing new approaches to the development of anabolic drugs
      for osteoporosis.
AB  - The understanding of cell interactions and genetic controls of bone cells has
      provided new approaches to drug development for osteoporosis. Current emphasis in
      the development of new anabolic therapies is directed at modifying the effects of
      Wnt signalling on osteoblast differentiation and bone formation. Local signalling
      that results in bone formation during remodelling takes place in several ways.
      Growth factors released from resorbed bone matrix can contribute to preosteoblast
      differentiation and bone formation. Osteoclasts in the bone multicellular units
      (BMUs) might also generate activity that contributes to bone formation. The
      preosteoblasts themselves, growing in the resorption space, can communicate
      through cell contact and paracrine signalling mechanisms to differentiate.
      Osteocytes can sense the need for bone repair by detecting damage and pressure
      changes, and signalling to surface cells to respond appropriately. These recent
      insights into cell communication, together with discoveries from human and mouse
      genetics, have opened new pathways to drug development for osteoporosis. With the
      anabolic effect of parathyroid hormone on the skeleton having been established,
      human genetics revealed the major role of Wnt signalling in bone formation, and
      this has become the target of activity. Current approaches include activation at
      any of several points in the Wnt pathway, and neutralization of sclerostin, the
      protein product of the SOST gene that is produced in osteocytes as a powerful
      inhibitor of bone formation.

PMID- 18338098
TI  - Effect of soft shell hip protectors on pressure distribution to the hip during
      sideways falls.
AB  - INTRODUCTION: While hip protectors represent a promising strategy for preventing
      hip fractures, clinical efficacy has been limited by poor user compliance. Soft
      shell protectors may be more acceptable to users than traditional hard shell
      designs. However, before embarking on clinical trials to assess efficacy,
      laboratory experiments are required to determine how soft shell protectors affect
      the force applied during impact to the hip. This was the goal of the current
      study. METHODS: Fifteen women participated in "pelvis release experiments," which
      safely simulate the impact stage of a sideways fall. During the trials, we
      measured total impact force and mean pressure over the greater trochanter with
      the participant unpadded, and while wearing two commercially available soft shell
      protectors. RESULTS: Mean pressure over the greater trochanter was reduced by 76%
      by a 14-mm thick horseshoe-shaped protector and by 73% by a 16-mm thick
      continuous protector. Total force was reduced by 9% by the horseshoe and by 19%
      by the continuous protector. CONCLUSIONS: Soft shell hip protectors substantially
      reduce the pressure over the greater trochanter, while only modestly reducing
      total impact force during simulated sideways falls. These data support the need
      for clinical trials to determine whether soft shell protectors reduce hip
      fracture risk in vulnerable populations.

PMID- 18338099
TI  - Routine versus targeted vertebral fracture assessment for the detection of
      vertebral fractures.
AB  - Fracture risk is underestimated in women with unknown vertebral fractures. Using
      VFA, we compared two screening methods: targeted (6,388 women) and routine (2,176
      women). Routine screening detected fractures in 20%. Targeted screening only
      required 5% attending for DXA to undergo VFA but only detected 9.6% of women with
      fractures. INTRODUCTION: BMD alone underestimates fracture risk in women with
      unknown vertebral fractures. We report the results of routine vertebral fracture
      assessment (VFA) screening and compare with targeted screening. METHOD: Our
      centre initially targeted VFA at women with reasons to suspect a vertebral
      fracture. Later we changed to routine VFA screening for all women over 65. We
      retrospectively compare each screening method's ability to detect vertebral
      fractures. RESULTS: Six thousand three hundred and eighty-eight women over 65
      underwent DXA during the period of targeted VFA and 2,176 during routine VFA.
      Routine VFA detected 420 (20.0%) women with fracture. Most vertebral fractures
      (56.2%) occurred in women with osteopenia. Routine VFA would be expected to alter
      the management of 1 in 6 osteopenic women. Targeted VFA was performed in 332
      (5.2%) women detecting 122 (1.9%) women with fractures. It was estimated that
      targeted VFA only detected 9.6% of women with a vertebral fracture. Targeted VFA
      failed to detect fractures in 18.1% of the population attending for DXA and in
      29% of those with osteoporosis. CONCLUSION: Routine VFA detects vertebral
      fractures in 20% of women over 65. Targeted VFA greatly reduces the number of
      VFAs performed but only detects a minority of the women with vertebral fractures.

PMID- 18338100
TI  - Multimedia archive of aesthetic plastic surgery techniques.

PMID- 18338101
TI  - Creativity in plastic surgery.

PMID- 18338102
TI  - Acellular dermis-assisted breast reconstruction.
AB  - BACKGROUND: In 2004, the authors reported their findings with placement of tissue
      expanders for breast reconstruction in the partial submuscular position, the
      equivalent of the "dual-plane" technique for breast augmentation. Limitations
      with subpectoral expander placement include difficulty controlling the lower pole
      of the pocket during expansion, unprotected device coverage by a thin inferior
      mastectomy flap, possible effacement of the inframammary fold, and limited
      control over the superior migration of the pectoralis major muscle. This study
      aimed to examine the safety and efficacy of an acellular dermal sling in
      providing inferolateral support to the device during immediate breast
      reconstruction and expansion. METHODS: This study prospectively investigated 58
      breasts of 43 consecutive women who underwent immediate breast reconstruction
      with tissue expanders and acellular dermis. After completion of adjuvant therapy
      and expansion, the devices were exchanged for implants. The patients were tracked
      through January, 2007. The study parameters included demographic information,
      oncologic data, complications, and aesthetic outcomes. RESULTS: The mean time
      required to complete reconstruction was 8.6 months. The overall complication rate
      after expander/acellular dermis placement was 12%, whereas the complication rate
      after exchange to implants was 2.2%. The aesthetic outcome for reconstructed
      breasts did not differ significantly from that for the control subjects who had
      no surgery. CONCLUSIONS: Acellular dermis appears to be a useful adjunct in
      immediate prosthetic breast reconstruction. Acellular dermis-assisted breast
      reconstruction has a low complication rate, helps to reconstruct an aesthetically
      pleasing breast, and facilitates expeditious completion of the reconstruction.

PMID- 18338103
TI  - Infragluteal sulcus: a combined histologic and anatomic reappraisal.
AB  - The infragluteal fold is one of the major concerns in reshaping of the gluteal
      region. This study reevaluated the fold both histologically and anatomically.
      Five fixed cadavers were used. The infragluteal fold on the right side was
      explored by dissection, whereas the infragluteal fold of the contralateral side
      was removed en bloc. Tissue samples (6 cm long x 2 mm thick) were taken at three
      points from each fold bloc: the most medial point, the middle point, and the most
      lateral end of the sulcus. Anatomic dissections and histologic examinations
      showed that the infragluteal fold consists of strong fibrous bands extending from
      the dermis of the medial one-third of the fold to the ramus of the ischium and
      sacrum, forming the letter J. The infragluteal fold, which attaches to both the
      ischium and the sacrum in a continuous fashion, is an anatomic structure in its
      medial part and only a crease laterally.

PMID- 18338104
TI  - Temperature-dependent growth and emergence of functional leaves: an adaptive
      mechanism in the seedlings of the western Himalayan plant Podophyllum hexandrum.
AB  - As an adaptive mechanism, hypocotyl dormancy delays emergence of functional leaf
      until favorable season of growth in Podophyllum hexandrum, an endangered
      medicinal plant of the western Himalayas. However, upon exposure of the freshly
      germinated seedlings to favorable temperature (25 degrees C), functional leaves
      emerged within 20 days. Therefore, we examined regulation mechanisms of growth
      and development of this alpine plant by temperature under laboratory conditions.
      The seedlings were exposed to (1) 25 degrees C (temperature prevailing at the
      time of maximum vegetative growth), (2) 4 degrees C (mean temperature at the
      onset of winter in its natural habitat), and (3) 10 degrees C (an intermediate
      temperature). Slackened growth at 4 degrees C was followed by senescence of
      aerial parts and quiescence of roots and predetermined leaf primordia. Rapid
      development of leaf primordia at 25 degrees C was associated with increased
      starch hydrolysis. This was evident from higher alpha-amylase activity and
      reducing sugars. These parameters decreased on sudden exposure to 4 degrees C. In
      contrast, the roots (perennating organs) showed a slight increase (1.36-fold) in
      alpha-amylase activity. Growth and development in seedlings growing at 10 degrees
      C (temperature less adverse than 4 degrees C) were comparatively faster. The
      content of reducing sugars and alpha-amylase activity were also higher in all the
      seedling parts at 10 degrees C as compared to 4 degrees C. This indicated larger
      requirements for sugar by the seedlings at 10 degrees C. Irrespective of
      temperature, maximum changes in nitrate and nitrate reductase occurred during the
      initial 10 days, i.e., when the readily available form of sugars (reducing sugar)
      was highest. This indicated that a temperature-dependent availability of carbon,
      but not temperature itself, was an important regulator of uptake and reduction of
      nitrogen.

PMID- 18338105
TI  - Bimanual anterior vitrectomy using a 25-gauge high-speed cutter to manage
      vitreous loss during phacoemulsification.
AB  - We examined the usefulness of bimanual anterior vitrectomy with a 25-gauge high
      speed cutter and infusion cannula for managing vitreous loss during
      phacoemulsification. Three eyes underwent phacoemulsification under topical
      anesthesia, during which, posterior capsule rupture occurred, resulting in
      vitreous loss and residual nuclear fragments. A 25-gauge high-speed cutter (2,500
      cuts/min) and a 25-gauge infusion cannula were inserted into the 3 and 9 o'clock
      ports. Anterior vitrectomy was performed by employing a bimanual technique. A
      viscoelastic substance and infusion cannula prevented nuclear fragments from
      falling into the vitreous. The cutter allowed the easy excision of nuclear
      fragments and sharp excision of the vitreous. The vitreous incarcerated in the
      iris at 12 o'clock was removed by manipulating the cutter like a spatula.
      Bimanual anterior vitrectomy, using a 25-gauge high-speed cutter and infusion
      cannula, allows effective excision of the lost vitreous, while preserving a
      closed anterior chamber under topical anesthesia.

PMID- 18338106
TI  - Nationwide study of hospitalization and surgical treatment for childhood
      strabismus in Italy between 1999 and 2004.
AB  - Surgery for strabismus is in decline in countries like the United Kingdom. The
      aim of the present study was to determine whether this trend is also present in
      Italy and, also, to ascertain the number of squint operations performed in a six
      year period. A retrospective review of all discharge summaries and procedures
      performed (diagnostic and therapeutic) for strabismus in Italian children aged 0
      14 years old in the period 1999-2004 was undertaken. The total number of surgical
      procedures was 21,204. The number (per 10,000) was 4.24 in 1999, 4.33 in 2000,
      4.31 in 2001, 4.25 in 2002, 4.23 in 2003, and 4.05 in 2004. The figure for 2004
      was reduced by 4.48% with respect to 1999 and by 6.46% with respect to 2000.
      Temporal analysis revealed that the total number of single-muscle procedures
      remained stable for the first two years and then decreased in 2001 and 2002, and,
      above all, in 2003 and 2004. No significant change was noted in the number of
      procedures involving two or more muscles. It is also noteworthy that very few
      operations for strabismus were performed on children less than one year of age.
      The trend revealed by our data cannot be compared to the overall reduction in
      strabismus surgery that has been observed in England and Ontario, but there was a
      moderate decrease in the frequency of single-muscle surgical procedures among
      Italian children aged 0-14 years old in 2003 and 2004. Further investigation is
      needed to determine how this trend has evolved since 2004.

PMID- 18338107
TI  - Ocular relapse in acute myeloid leukemia (M4) with normal bone marrow.
AB  - A patient with the rare occurrence of ocular relapse of acute myeloid leukemia
      (AML) M4 while the bone marrow was normal is reported in this paper. A 47-year
      old woman with AML was treated with chemotherapy and went successfully into
      remission. Four months later, she presented with pain, redness, and a mass over
      the left eye. The ocular relapse involved the subconjunctival space and anterior
      chamber of the left eye and, presumably, the left lacrimal gland. There were also
      multiple subcutaneous nodules on both of her forearms. Incisional biopsy from the
      subconjunctival lesion was performed. Histopathological examination of the
      specimen showed diffuse blast cell infiltration. Her bone marrow was still in
      remission. Although exceedingly rare, ocular extramedullary relapse in AML M4
      heralds bone marrow recurrence and, despite intensive chemotherapy, the prognosis
      is dismal.

PMID- 18338108
TI  - Erythropoietin in heart and vessels: focus on transcription and signalling
      pathways.
AB  - Erythropoietin (Epo) is synthesized mainly under hypoxic conditions by renal and
      extrarenal tissues, including liver, spleen, brain, lung, bone marrow, and
      reproductive organs. Hypoxia abrogates the degradation of hypoxia-inducible
      factors (HIF)-1 and -2, that can then bind to the hypoxia response element within
      the Epo gene, activating its transcription. Receptors for Epo are expressed on
      cells known to synthesize Epo, but also on cardiomyocytes, cardiac fibroblasts,
      and endothelial, retinal, gastric, prostate and vascular smooth muscle cells. Epo
      receptor binding triggers at least three intracellular signalling cascades: (1)
      janus tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 5
      (STAT5); (2) phosphatidylinositol-3 kinase (PI3K)/Akt, and (3) RAS/mitogen
      activated protein kinase (MAPK). Epo also enhances nitric oxide (NO)
      bioavailability through endothelial NO synthase transcription and activation, and
      exerts antiapoptotic actions through Bcl-2 and Bcl-XL. NO is a powerful
      vasodilator, insulin-sensitizer, inhibitor of atherothrombosis and apoptosis, and
      essential for progenitor mobilization. This article is a concise review of recent
      advances regarding the molecular and cardiovascular effects of Epo.

PMID- 18338110
TI  - A descriptive evaluation of warfarin use in patients receiving hospice or
      palliative care services.
AB  - PURPOSE: To describe and compare warfarin therapy use and outcomes between
      warfarin-receiving patients in hospice or palliative care (HPC) and not in HPC.
      METHODS: This retrospective, matched analysis examined warfarin-receiving
      patients who did (study cohort) and did not receive (control cohort) HPC services
      between 2002 and 2005. The matched cohorts were compared on rates of
      international normalized ratio (INR) measurements, INR control, and warfarin
      related adverse events. RESULTS: Included were 101 and 484 study and matched
      control patients, respectively. Study patients had a higher mean rate of INR
      measurements per 30 days (2.2 +/- 1.7 vs. 1.7 +/- 1.4, P = 0.001) and were more
      likely to be above and below target INR range (P < 0.05) than control patients.
      Differences between the cohorts in incidences of warfarin-related adverse events
      were not statistically significant (P > 0.05). CONCLUSIONS: Patients in HPC
      required more frequent INR monitoring but had similar risks for warfarin-related
      adverse events.

PMID- 18338109
TI  - Effectiveness and safety of a management protocol to correct over-anticoagulation
      with oral vitamin K: a retrospective study of 1,043 cases.
AB  - BACKGROUND: Timely reversal of excessive anticoagulation is important in
      preventing bleeding complications. The use of vitamin K in correcting over
      anticoagulation is widely accepted to be superior to discontinuation of therapy
      but its effectiveness and safety in large scale cohort studies has not been
      assessed. METHODS: According to our protocol, 2 mg of oral vitamin K in addition
      to omitting the day's dose of warfarin, were administered to all patients
      presenting INR levels >or=5.0 and below 10.0; the INR values were checked 20 h
      after vitamin K administration. The rate of decay of INR, bleeding and
      thromboembolic complications at presentation and the following 30 days, as well
      as resistance to warfarin were assessed. RESULTS: Of the 1,611 events, 1,043 (878
      patients) met the selection criteria. The median (interquartile range) INR was
      6.64 (6.12-7.52) at presentation (day zero) and fell to a median (interquartile
      range) INR of 2.72 (2.18-3.52, P < 0.0001) after the vitamin K administration
      (day one) and 90.6% of the INRs were below 4.5. In 98 (9.4%) instances the INR
      values did not fall below the safe limit of 4.5 and in 173 (17%) instances the
      INR values were overcorrected to below 2.0. Median INR value on day zero in these
      two groups was higher (7.3 vs. 6.6, P < 0.0001) and lower (6.5 vs. 6.7, P =
      0.049) than that of the remaining cases, respectively. Overcorrection occurred
      more frequently in women (P = 0.0002). Female gender was an independent factor
      associated with INR overcorrection (P = 0.001; OR = 1.7, 95% CI 1.3-2.3). The
      INRs on day one were inside, above and below the therapeutic range in 44%, 36%
      and 20% respectively. Warfarin resistance was observed in six cases (0.6%). Major
      bleeding was reported in one case (1.1 per 100 patient-years), minor bleeding in
      14 cases (16.1 per 100 patient-years) and thromboembolic events in six high risk
      patients (6.9 per 100 patient-years) during the one month period following
      vitamin K administration. CONCLUSIONS: This adopted protocol for the reversal of
      excessive anticoagulation in asymptomatic or minor symptom presenting patients is
      easily applied, effective in lowering the INR and preventing complications. Its
      use in high risk thromboembolic patients warrants caution.

PMID- 18338111
TI  - Sonoelectrochemical deposition of calcium phosphate coatings on carbon materials-
      effect of electrolyte concentration.
AB  - Calcium phosphate was deposited on carbon materials using a sonoelectrochemical
      method in an electrolyte containing calcium and phosphate ions. The effect of
      electrolyte concentration on sonoelectrochemically deposited calcium phosphate
      coatings was investigated and the underlying deposition mechanisms were
      discussed. The morphology, size and composition of the crystalline deposits
      changed with the electrolyte concentration. A mixture of plate, sphere and needle
      like deposits was obtained at Ca(2+) ion concentrations greater than 16 mM,
      however needle-like hydroxyapatite (HA) was obtained at lower Ca(2+)
      concentrations. Analysis revealed that the sonoelectrochemical deposition of
      calcium phosphate consists of two processes-nucleation and crystal growth. The
      results suggest that the homogeneous nucleation of calcium phosphates in
      solution, followed by their absorption onto the carbon surface may account for
      the mechanism of coating observed at higher ionic concentrations. At lower
      concentrations, heterogeneous nucleation occurs on the surface of the carbon
      fibres, followed by the development of islands of crystal growth. The lower ionic
      concentration was shown to favour the generation of hydroxyapatite on carbon
      based materials.

PMID- 18338112
TI  - Zinc in thalassemic patients and its relation with depression.
AB  - Studies have shown that there is a relationship between zinc levels and
      depression. Thalassemic patients are at risk of zinc deficiency due to various
      causes including Desferal injection. The aim of this study, therefore, is to
      investigate hair zinc levels in thalassemic patients and their association with
      depression. For the purposes of this survey, 50 patients with major thalassemia
      between 10-20 years old were selected randomly. The patients' hair zinc
      concentration was compared with a control group of similarly aged healthy
      individuals. Simultaneously, their psychological status was evaluated with either
      the "Beck" or "Marya Kovacs" test (according to age) so that the relation between
      depression and zinc concentration could be assessed. The mean hair zinc
      concentration in patients was more than the controls (193.96 +/- 92.4 ppm vs
      149.6 +/- 72.21 ppm). Zinc deficiency was present in 10% of the patients, and 52%
      had some degree of depression. There was a reverse correlation between zinc
      deficiency and blood transfusion rate (p < 0.05). Also, while there were more
      incidences of depression among the zinc deficient patients, the difference was
      not significant. Regarding the high prevalence of depression and insignificant
      relation to the zinc deficiency in these thalassemic patients, this research
      suggests the need for further consideration concerning patients' psychological
      status, the risk factors of zinc deficiency, as well as extended assessment into
      other causes of depression.

PMID- 18338114
TI  - [A special instrument: the halo fixator].
AB  - OBJECTIVE: Installation of an external fixator in combination with a body cast
      for temporary or definitive immobilization and retention of unstable fractures of
      the craniocervical junction and upper part of the cervical spine. Further
      established applications include presurgical extension treatment of paralytic
      scoliosis and temporary retention within complex spine deformity operations after
      ventral release or mobilized osteotomies. INDICATIONS: Closed reposition and
      temporary retention of unstable injuries of the cervical spine up to operation.
      Extension treatment for careful reposition of fresh or dated malpositions of the
      cervical spine. Conservative treatment of injuries of the craniocervical junction
      and the upper part of the cervical spine. Presurgical extension of paralytic
      scoliosis. Temporary extension after ventral release. CONTRAINDICATIONS: Cranial
      fractures and intracranial injuries. Soft-tissue infections of the skull.
      Children < 3 years. Adiposity, chest injuries and paraplegia as relative
      contraindications using the halo body cast. SURGICAL TECHNIQUE: Halo traction is
      applied in two stages; first, the head ring is attached to the skull, then, the
      body cast and suspension assembly are added. Local anesthesia, depending on
      circumstances. Sizing of the components; the optimal size of the ring is about
      1.5" larger than the circumference of the patient's head. Patient in sitting or
      supine position. The halo ring is held in proper position by stabilizer plates;
      the lower margin of the ring should be just above the ears and about 0.4" above
      the eyebrows. The anterior pins are placed in shallow groove on the forehead
      between supraorbital ridges and frontal protuberances. Threaded skull pins are
      screwed with defined torque (4-8"/pounds) in the lamina externa of the cranial
      calotte without perforating the lamina interna. To avoid side-to-side drifting,
      the diagonally opposite pins should be tightened simultaneously. Finally,
      connection of the halo ring with a body cast or putting on an extension device.
      RESULTS: Secure external stabilization of unstable injuries of upper cervical
      spine. Improvement of correction results of patients with neuromuscular scoliosis
      who underwent surgical treatment. Disadvantages are procedure-specific
      complications (infection and loosening of head pins) with different published
      frequencies and decreased patient's acceptance at longer therapy duration.

PMID- 18338115
TI  - [Primary treatment of acute extensor tendon injuries of the hand].
AB  - OBJECTIVE: Reconstruction of extensor functions after extensor tendon injuries of
      the hand. INDICATIONS: Acute injuries of extensor mechanism with corresponding
      loss of function. CONTRAINDICATIONS: Complex injuries with loss of soft tissue.
      Limited possibility of extensor tendon reconstruction with combined injuries of
      the interphalangeal joints (in situations with irreparable joints: primary
      arthrodesis). SURGICAL TECHNIQUE: The treatment of extensor tendon injuries
      depends on the various levels of tendon laceration. Zones 1 and 2: in case of
      tendon disruption close to the base of the distal phalanx, refixation of tractus
      terminalis using a pull-out suture. In case of disruption more proximally,
      primary repair using mattress sutures. Temporary pinning of the distal
      interphalangeal joint in extension using a single transarticular Kirschner wire.
      Zone 3: mattress sutures of the tractus intermedius. Temporary pinning of the
      proximal interphalangeal joint in extension using a single transarticular
      Kirschner wire. Zone 4: reconstruction of the central slip and the lateral slip
      of extensor tendon using modified Becker sutures and mattress sutures. Temporary
      pinning of the proximal interphalangeal joint in extension using a single
      transarticular Kirschner wire. Zones 5 and 6: four-strand modified Becker sutures
      with additional epitendinous suture. Zones 7 and 8: core sutures using modified
      Kirchmayr techniques with additional epitendinous suture. POSTOPERATIVE
      MANAGEMENT: Zones 1-4: immobilization of the finger for 6 weeks with removal of
      the transarticular wire at 4 weeks. Zones 5-8: dynamic postoperative treatment in
      intrinsic-plus splint for 6 weeks. RESULTS: It is postulated that dynamic
      postoperative treatment leads to improved functional outcome after extensor
      tendon injuries. While for zones 1-4 no better final clinical results are
      observed using the dynamic postoperative protocol, early protected motion for
      zones 5-8 is superior to static post operative treatment.

PMID- 18338116
TI  - [Modified technique of trapezius transfer to improve function in brachial plexus
      palsy].
AB  - OBJECTIVE: Increase of shoulder stability. Elimination of inferior subluxation of
      the humeral head. Increase of active abduction. Better control of the paralyzed
      arm. Decrease or elimination of shoulder pain. INDICATIONS: Palsy of deltoid and
      supraspinatus muscles with weak abduction, multidirectional shoulder instability
      and subluxation of the humeral head after complete neurosurgical therapy
      (neurolysis, reconstruction of the brachial plexus). No essential active function
      of the elbow and hand. CONTRAINDICATIONS: Weakness of trapezius muscle.
      Incomplete rehabilitation after neurosurgical procedure. Stiffness of the
      glenohumeral joint. Arthritis of the glenohumeral joint. SURGICAL TECHNIQUE: The
      cranial part of the trapezius muscle is detached from the scapular spine and the
      clavicle. Its insertion at the acromion is left untouched. The acromion is freed
      from the scapular spine and the lateral end of the clavicle by oblique
      osteotomies and then transferred to the proximal humerus. Under maximum tension
      the deltoid muscle is sutured on top of the trapezius muscle. POSTOPERATIVE
      MANAGEMENT: Immobilization of the arm in an abduction support (75 degrees of
      abduction) for 6 weeks. The physiotherapy program starts on the 1st postoperative
      day with assisted and active training of elbow, hand, and fingers. During the 1st
      postoperative week, the abduction support is removed for physiotherapy, abduction
      is maintained during the exercises. After 6 weeks, progressive adduction to
      remove the abduction support is commenced. RESULTS: The procedure was performed
      in 104 cases. 80 patients were followed up on average after 2.4 years (0.8-8
      years). In all cases, the transfer resulted in an increase of function and in 95%
      in a decrease of multidirectional shoulder instability. The modification of the
      original technique in the latest 22 cases was superior in terms of shoulder
      stability. In all these cases, a decrease of instability was achieved and
      inferior subluxation was abolished.

PMID- 18338117
TI  - [Modified Ishiguro extension block technique for fracture-dislocation of the
      distal interphalangeal joint].
AB  - OBJECTIVE: Reconstruction of the anatomic configuration of the articular surface
      and restoration of complete movement of the finger joint. INDICATIONS: Fracture
      of the distal interphalangeal (DIP) joint involving > or = 30% of the articular
      surface. Luxation or subluxation of the distal phalanx. Fracture-dislocation > or
      = 2 mm. CONTRAINDICATIONS: Old fractures. Closed reduction impossible. SURGICAL
      TECHNIQUE: Closed reduction and pin fixation modified from Ishiguro technique
      without penetrating the fracture fragment. POSTOPERATIVE MANAGEMENT: Cast
      fixation for 4 weeks with the finger in functional position or with the proximal
      interphalangeal joint flexed to relax the pulley. After 4 weeks, removal of the
      cast and the pin and start of active motion exercises. RESULTS: Twelve patients
      with fracture-dislocation of the DIP joint involving more than one third of the
      articular surface were treated with the modified extension block technique
      according to Ishiguro. Time from injury to surgery was 5 days (range, 0-8 days).
      At a mean follow-up of 15 months (range, 9-31 months), pain on the visual analog
      scale (VAS, 0 = no pain, 10 = maximum pain), the active range of motion, and
      criteria according to Warren et al. were evaluated. Eleven patients were pain
      free and one patient suffered from mild pain during strenuous work. The mean
      active range of motion was from -3 degrees extension (range, 0-10 degrees ) and
      flexion to 79 degrees (range, 45-100 degrees ). The results according to Warren
      et al. were very good in ten and good in two cases.

PMID- 18338118
TI  - [Acute flexor tendon surgery].
AB  - OBJECTIVE: Flexor tendon repair by direct suture, providing tendon function and
      mechanical properties and allowing postoperative active extension and flexion.
      INDICATIONS: Flexor tendon laceration in all zones, when primary healing and a
      good functional outcome can be expected. CONTRAINDICATIONS: Florid and chronic
      infection. Lack of skill, instruments, or manpower. Tension-free suture is not
      feasible. Severe soft-tissue problems. Mantero suture in case of coexistent
      artery injury. SURGICAL TECHNIQUE: Hand surgical incisions and approach to the
      tendon. Opening of the tendon sheath in the region of oblique pulley. A four
      strand core suture consisting of two locked two-strand sutures and a
      circumferential epitendon cross-stitch suture are performed. Lacerations in zone
      I with a tendon stump shorter than 1 cm require a Mantero suture and avulsions
      require a pull-out suture technique. POSTOPERATIVE MANAGEMENT: Active flexion and
      active extension in a dorsal wrist cast. RESULTS: The clinical outcome studies
      after repair of zone II flexor tendon injuries using a multiple-strand suture
      technique describe 69-96% excellent and good results.

PMID- 18338119
TI  - [Transosseous repair of patellar tendon ruptures].
AB  - OBJECTIVE: Restoration of active knee extension. Restoration of active knee
      stabilization. Avoiding secondary patella alta. INDICATIONS: Acute rupture of the
      patellar tendon within 3-5 days. Chronic rupture of the patellar tendon.
      CONTRAINDICATIONS: Compromised general health status or associated injuries.
      Compromised local soft-tissue situation. SURGICAL TECHNIQUE: Exposure of the
      ruptured tendon. Coronal drill hole through the distal third of the patella and
      coronal drill hole through the tibial tuberosity. After anatomic positioning of
      the patella (adjusting correct height), patellotibial fixation with monofil or
      woven (Labitzke) cerclage wire or PDS cord. Suture repair of the patellar tendon
      and repair of the ruptured medial and lateral retinaculum. Drain insertion. Wound
      closure in layers. POSTOPERATIVE MANAGEMENT: Full load bearing in cylinder cast.
      Week 0-2: flexion restricted to 30 degrees , quadriceps muscle isometry. Week 2
      4: flexion restricted to 60 degrees , strengthening of hip abductors and
      extensors. Week 4-6: flexion restricted to 90 degrees . After week 6: removal of
      cylinder cast. After week 12: return to sporting activities, removal of the
      cerclage wire. RESULTS: Good results after surgical therapy. Low rate of
      secondary rupture. Low rate of muscle weakness.

PMID- 18338120
TI  - [Transpatellar refixation of acute quadriceps tendon ruptures close to the
      proximal patella pole using FiberWire].
AB  - OBJECTIVE: Reconstruction of the extensor mechanism of the knee joint by stable
      suture of the quadriceps tendon. Early functional treatment. INDICATIONS: Acute
      or partial disruption of the quadriceps tendon close to the proximal patella pole
      with loss of extensor function of the knee joint. CONTRAINDICATIONS: Open rupture
      of the quadriceps tendon with extended soft-tissue damage and high risk of or
      ongoing inflammation until healing of the soft tissues. Chronic quadriceps tendon
      rupture. Ruptures at the musculotendinous junction. SURGICAL TECHNIQUE: Supine
      positioning of the patient on a standard operating table with the knee in 30
      degrees of flexion. Securing of the proximal tendon stump with two Bunnell
      sutures using no. 2 Fiber-Wire (Arthrex GmbH, Karlsfeld/Munich, Germany).
      Creation of a transverse, central trough in the superior pole of the patella.
      Transosseous refixation of the quadriceps tendon through longitudinal
      transpatellar drill holes. Intraoperative evaluation of the stability of the
      suture at 60 degrees of flexion. Repair of the retinacula with multiple
      interrupted sutures. POSTOPERATIVE MANAGEMENT: Partial weight bearing (15-25 kg)
      for 6 weeks. Knee orthesis for 6 weeks, with increase of the initially allowed
      flexion of 30 degrees every 2 weeks by another 30 degrees . Initially, continuous
      passive motion (CPM) and passive movement exercises up to 60 degrees of flexion.
      After discharge from hospital, outpatient physical therapy with prone active
      flexion exercises. At the beginning of the 5th week, start with active and
      passive extension of the knee joint. From the 7th week on, full weight bearing is
      allowed and coordinative and strengthening exercises should be commenced. Sport
      activities can gradually be taken up after 3 months. RESULTS: Early diagnosis,
      timely surgical repair and early functional treatment are important for the
      outcome of quadriceps tendon ruptures. With the presented method, ruptures close
      to the upper patella pole can be treated. The majority of quadriceps tendon
      ruptures takes place in this area since the avascular zone found here predisposes
      to degenerative changes.

PMID- 18338121
TI  - [Closing-wedge high tibial osteotomy with a modified Weber technique].
AB  - OBJECTIVE: Deceleration of the progression of medial gonarthritis via transfer of
      the mechanical load axis from the medial to the lateral femorotibial compartment
      and by reduction of compressive stresses in the medial compartment. INDICATIONS:
      Isolated early-stage unicompartmental medial gonarthritis. Symptomatic varus
      deformity. Adjustment of the mechanical load axis in reconstructive surgery such
      as autologous chondrocyte transplantation. Correction of posttraumatic varus
      deformities. CONTRAINDICATIONS: Concomitant patellofemoral arthritis, lateral
      femorotibial arthritis, or other painful conditions of the knee. Limited range of
      motion. Knee instabilities, since a rapid development of a tricompartmental
      gonarthritis is likely to occur. Advanced osteoporosis. Poor peripheral
      circulation with an absent foot pulse. Lateral meniscectomy. SURGICAL TECHNIQUE:
      Lateral approach. Subcapital osteotomy of the fibula. Preparation of the lateral
      tibial head. Partial osteotomy of the proximal one third of the tibial
      tuberosity. Marking of the joint line. A semitubular plate is placed over a guide
      wire parallel to the joint line, 1.5 cm distal to it, and is gently hammered into
      the tibial head with just the last hole seen outside. The lateral end of the
      plate is bent downward. Ascending osteotomy of the tibial head in an
      inferolateral to craniomedial direction. The osteotomy starts 2.5 cm distal to
      the plate and ends directly below the guide wire. The medial cortex remains
      intact. Excision of a lateral-based bone wedge according to the preoperative
      planning. The osteotomy is gently closed under valgus stress. A 4.5-mm cortical
      screw is aimed through the lateral hole of the plate into the distal fragment of
      the tibia and tightened until the osteotomy is brought under compression.
      POSTOPERATIVE MANAGEMENT: During hospitalization, there is a periodic treatment
      with continuous passive motion without any limitation of range of motion and
      isometric training is taken up. Mobilization is permitted with partial load of 15
      kg with two crutches during 6 weeks postoperatively. Ambulatory physical training
      with active and passive motion exercises. After 6 weeks, the load can be
      increased stepwise depending on the consolidation as seen on the control
      radiographs. Full weight bearing is generally reached after 10 weeks. During this
      time, thromboembolism prophylaxis with low-molecular-weight heparin is necessary.
      RESULTS: A retrospective analysis of the own patients treated with the described
      surgical technique was performed. On the basis of Kaplan-Meier survival analysis,
      it could be demonstrated that there is a correlation between the patients' level
      of activity and the long-term survival rate 10-15 years after the osteotomy.
      Moreover, the extent of correction has a direct influence on the long-term
      result.

PMID- 18338122
TI  - Minimally invasive retrocapital osteotomy of the first metatarsal in hallux
      valgus deformity.
AB  - OBJECTIVE: Percutaneous retrocapital distal osteotomy of the first metatarsal for
      surgical treatment of hallux valgus. INDICATIONS: Mild to moderate hallux valgus
      deformity in both juveniles and adults. Recurrent hallux valgus deformity after
      previous surgery. CONTRAINDICATIONS: Severe degenerative changes of the first
      metatarsophalangeal joint (hallux valgus et rigidus). Previous Keller's
      procedure. SURGICAL TECHNIQUE: A percutaneous distal linear osteotomy of the
      first metatarsal is performed and stabilized with a Kirschner wire. The surgical
      technique follows these steps: distal Kirschner wire insertion; skin incision;
      sparse periosteal detachment; distal retrocapital osteotomy of the first
      metatarsal; correction of the first intermetatarsal angle by lateral displacement
      of the capital fragment; stabilization with Kischner wire insertion into the
      proximal metatarsal; postoperative taping. RESULTS: The patients were satisfied
      following 107 (91%) of 118 consecutive percutaneous procedures with a follow-up
      of 35.9 months (range 24-78 months). According to the American Orthopaedic Foot
      and Ankle Society (AOFAS) hallux metatarsophalangeal-interphalangeal scale for
      the clinical assessment, a mean score of 88.2 +/- 12.9 was obtained at follow-up.
      The clinical results can be compared to those obtained with open techniques, with
      the advantages of a minimally invasive procedure.

PMID- 18338123
TI  - CT-guided percutaneous transthoracic biopsy in the diagnosis of mediastinal
      masses: evaluation of 73 procedures.
AB  - PURPOSE: This study was performed to evaluate the factors affecting the
      diagnostic accuracy and rate of complications of CT-guided percutaneous
      transthoracic needle biopsy of mediastinal masses. MATERIALS AND METHODS: We
      reviewed 73 consecutive mediastinal biopsies in 70 patients. Final diagnoses were
      based on a retrospective analysis of surgical outcomes, results of repeat
      biopsies or findings of imaging and clinical follow-up lasting at least 4 months.
      Benign and malignant biopsy findings were compared with the final outcomes to
      determine the diagnostic accuracy of the method. Finally, we analysed the
      complications. RESULTS: CT-guided percutaneous transthoracic needle biopsy
      provided adequate samples in 61/73 cases, with a total sample rate of 83.6%. Of
      these 61 biopsies, 51 yielded a correct diagnosis with specific histological
      typing, mainly in the case of thymoma and metastasis. Lymphomas were less
      reliably diagnosed. The overall sensitivity, specificity, positive predictive
      value, negative predictive value and diagnostic accuracy values were 83.6%, 100%,
      100%, 35.3% and 83.6%, respectively. Pneumothorax was the most common
      complication (5.5%). CONCLUSIONS: CT-guided percutaneous transthoracic needle
      biopsy is an easy, reliable and safe procedure that obviates the need for
      exploratory surgery in medically treatable or unresectable cases. It should be
      the first invasive procedure in the diagnostic workup of mediastinal masses.

PMID- 18338124
TI  - Radiological aspects of diffuse alveolar haemorrhage.
AB  - PURPOSE: This paper describes chest X-ray (CXR) and computed tomography (CT)
      findings of diffuse alveolar haemorrhage (DAH). MATERIALS AND METHODS: We
      retrospectively reviewed 23 episodes of DAH in 20 patients, 17 of known aetiology
      and three of unknown aetiology. All cases were studied by CXR and 15 also by CT.
      Parenchymal consolidations and ground-glass opacities were evaluated after
      dividing each lung into three regions (upper, middle, lower) for a total of six
      zones. RESULTS: Consolidations or ground-glass opacities were identified on CXR
      in 16/20 patients, mainly in the middle fields (73%). In 4/20 patients, all with
      Wegener's granulomatosis, CXR was negative or demonstrated only nodular
      opacities; in two of these cases, CT revealed ground-glass opacities. A complete
      follow-up was available for ten patients: initially, they showed consolidation
      opacities in 36/60 zones, which persisted in 16/60 after 7 days and in 11/60
      after 15 days. Conversely, ground-glass opacities increased after 7 days owing to
      the partial regression of consolidation opacities, and they markedly diminished
      after 15 days. CONCLUSIONS: DAH is radiologically characterised by a nonspecific
      alveolar-filling pattern. Diagnosis or suspicion of DAH needs to be supported by
      the evidence of haemoptysis and/or rapid-onset anaemia. CT is superior in
      detecting ground-glass opacities and is required in cases of suspected DAH with
      normal CXR findings.

PMID- 18338125
TI  - Automated volumetry of pulmonary nodules on multidetector CT: influence of slice
      thickness, reconstruction algorithm and tube current. Preliminary results.
AB  - PURPOSE: To evaluate the influence of slice thickness, reconstruction algorithm
      and tube current (mA) on the performance of a software package in determining the
      volume of solid pulmonary nodules on multidetector-row computed tomography
      (MDCT). MATERIALS AND METHODS: A chest phantom containing artificial solid
      nodules with known volume was imaged with two MDCT scans at 100 and 40 mAs (200
      mA and 80 mA, 0.5-s rotation time), respectively. Data were reconstructed with
      slice thicknesses of 1.25 and 2.5 mm and five different algorithms. The volumes
      of three nodules (juxtavascular, intraparenchymal, juxtapleural) were calculated
      using three-dimensional (3D) volumetric software. Differences between estimated
      and real volume were reported for each nodule and reconstruction set. RESULTS:
      The software segmented all nodules on 1.25-mm-thick reconstructions,
      independently from the mAs. It did not segment the juxtapleural nodule on 2.5-mm
      thick reconstructions at 40 mAs. Mean values of the differences, which better
      approximated the real volume of the nodules, were obtained with high-spatial
      resolution algorithms on both 100 and 40 mAs images at 1.25-mm slice thickness.
      CONCLUSIONS: Slice thickness, reconstruction algorithm and tube current can
      affect the 3D volume measurement of solid nodules. The best performance of the
      software, on both 100 and 40 mAs images, was observed with a slice thickness of
      1.25 mm and high-spatial-resolution algorithms.

PMID- 18338126
TI  - High-resolution computed tomography evaluation of airway distensibility in
      asthmatic and healthy subjects.
AB  - PURPOSE: Airway-wall remodelling may result in reduced airway distensibility in
      bronchial asthma. This study evaluated the baseline airway calibre and
      distensibility in asthmatic patients by means of high-resolution computed
      tomography (HRCT). MATERIALS AND METHODS: We studied seven patients (two men, age
      range 36-69 years) with chronic asthma [forced expiratory volume in the first
      second (FEV(1)) range: 30%-87% of predicted; FEV1/forced vital capacity (FVC)
      range 48%-75% of predicted) under stable clinical conditions and six healthy
      control subjects (three men, age range 29-50 years). In all subjects, HRCT
      scanning, at suspended end-expiratory volume, was performed at rest and during
      ventilation with 6 and 12 cmH(2)O by nasal insufflation with continuous positive
      airway pressure (nCPAP), both at baseline and after inhalation of 200 mug
      oxitropium bromide metered dose inhaler (MDI). External and lumen diameter (mm)
      of the right apical upper lobe bronchus were measured in all HRCT scans. RESULTS:
      In asthmatics, 12 cmH(2)O insufflation significantly changed baseline lumen
      (3.3+/-0.7 mm vs. 3.8+/-0.6 mm; p<0.01) and external diameter (6.2+/-0.9 mm vs.
      6.7+/-0.8 mm; p<0.05), whereas in healthy controls, both 6 and 12 cmH(2)O
      insufflation significantly changed baseline lumen diameter (4.0+/-1.6 mm vs.
      4.8+/-1.6 mm and 4.7+/-1.7 mm; p<0.01). In asthmatic patients, oxitropium bromide
      inhalation significantly changed baseline lumen diameter (3.3+/-0.7 mm vs. 4.4+/
      0.6 mm; p<0.05), whereas the application of 6 or 12 cmH(2)O insufflation did not
      modify any bronchial diameters. In healthy controls, oxitropium bromide
      inhalation significantly changed baseline lumen diameter (4.0+/-.6 mm vs. 5+/-1.5
      mm; p<0.05). The application of 12 cmH(2)O but not of 6 cmH(2)O induced a
      significant change in lumen diameter (5.0+/-1.5 mm vs. 6,0+/-1.6 mm; p<0.05).
      CONCLUSIONS: Our results show that airway distensibility in asthmatic patients,
      as assessed by HRCT, can differ compared with that of healthy controls. HRCT can
      provide useful information on airway distensibility.

PMID- 18338127
TI  - MR spectroscopy of the breast.
AB  - This literature review assesses the clinical potential of proton ((1)H) magnetic
      resonance spectroscopy (MRS) of breast lesions. We here illustrate the basic
      principles of spectrum acquisition for volumes of interest, determined on the
      basis of dynamic magnetic resonance imaging (MRI) and of MRS postprocessing. We
      discuss the criteria for interpreting the spectrum with particular reference to
      the metabolic significance of the peak of total choline containing compounds at
      3.2 ppm, a marker that is correlated with malignancy. We then summarise the
      findings obtained in lesion characterisation (with a possible gain in specificity
      with respect to dynamic MRI), the assessment of the effects of neoadjuvant
      chemotherapy and the correlation reported at high-field between the tumour tissue
      concentration of choline-containing compounds and the presence of lymph node
      metastases. Lastly, we outline the clinical use of this technique as the final
      phase of a complete breast MR examination after intravenous administration of
      paramagnetic contrast material for the dynamic study, with reference to its use
      by radiologists dedicated to breast imaging.

PMID- 18338128
TI  - Stereotactic vacuum-assisted breast biopsy in 268 nonpalpable lesions.
AB  - PURPOSE: We evaluated the reliability of stereotactic vacuum-assisted breast
      biopsies (VAB) from our personal experience. MATERIALS AND METHODS: Between
      January 2003 and December 2005, 268 patients underwent VAB with an 11-gauge probe
      at our institution. Inclusion criteria were nonpalpable lesions, undetectable by
      ultrasound and suspected at mammography (microcalcifications, circumscribed mass,
      architectural distortion), for which cytology and/or core biopsy could not
      provide a definite diagnosis. Lesion mammographic patterns were
      microcalcifications in 186 cases (77.5%), mostly localised clusters (130/186:
      70%); circumscribed mass with or without microcalcifications in 36 cases (15%)
      and architectural distortion with or without microcalcifications in 18 cases
      (7.5%). On the basis of the Breast Imaging Reporting and Data System (BI-RADS)
      classification, 16 cases (7%) were graded as highly suspicious for malignancy (BI
      RADS 5), 81 (34%) as suspicious for malignancy (BI-RADS 4b), 97 (40%) as
      indeterminate (BI-RADS 4a) and 46 (19%) as probably benign (BI-RADS 3). Lesion
      size was <or=10 mm in 161 cases (67%) and >20 mm in only 38 cases (16%), 30 of
      which appeared as microcalcifications. RESULTS: In 28/268 lesions (10.5%) the
      biopsy could not be performed (nonidentification of the lesion; inaccessibility
      due to location or breast size). In 12/240 (5%) biopsies, the sample was not
      representative. Pathology revealed 100/240 (42%) malignant or borderline lesions
      and 140/240 (58%) benign lesions. Among the malignant lesions, 16/100 (16%) were
      invasive carcinoma [infiltrating ductal carcinoma (IDC) or infiltrating lobular
      carcinoma (ILC)], 13/100 (13%) were microinvasive (T1mic), 35/100 (35%) were
      ductal carcinoma in situ (DCIS), 9/100 (9%) were lobular carcinoma in situ
      (CLIS). Among the borderline lesions, 27/100 (27%) were atypical epithelial
      hyperplasia [atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia
      (ALH)]. In 9/100 surgically treated lesions (9%), there was discordance between
      the microhistological findings of VAB and the pathological results of the
      surgical procedure: 8/9 were underestimated by VAB (four ADH vs. DCIS, three DCIS
      vs. IDC, one ADH vs. IDC), and 1/9 was overestimated (T1mic vs. DCIS).
      Complications following VAB occurred in 9/240 patients (3.7%). CONCLUSIONS: In
      our experience, VAB showed fair reliability in the diagnosis of nonpalpable
      breast lesions despite a portion of failed (10.5%), nonsignificant (5%)
      procedures and underestimated lesions (9%).

PMID- 18338129
TI  - Intrahepatic peripheral cholangiocarcinoma (IPCC): comparison between perfusion
      ultrasound and CT imaging.
AB  - PURPOSE: This study was done to compare the perfusion patterns of intrahepatic
      peripheral cholangiocarcinoma (IPCC) on contrast-enhanced ultrasound (CEUS) and
      dynamic computed tomography (CT). MATERIALS AND METHODS: We retrospectively
      reviewed 23 histologically proven cases of IPCC. All lesions were studied by CEUS
      with sulfur hexafluoride-filled microbubbles coated with a phospholipid capsule,
      and by dynamic CT. Contrast-enhancement patterns were evaluated in the arterial
      phase (CEUS 10-20 s after the injection; CT 25-30 s after the injection) and in
      the delayed phase (CEUS 120 s after the injection; CT>2-3 min after the
      injection). RESULTS: Lesions were single in 18/23 cases (78%), single with nearby
      satellite lesions in 1/23 (4%) cases and multifocal with distant secondary
      lesions in 4/23 (17%) cases. Lesion diameter was 2-5 cm in 7/23 cases (30%), 5-7
      cm in 13/23 cases (57%) and >7 cm in 3/23 (13%) cases. On CEUS, lesions were
      hypervascular in 16/23 cases (70%). On delayed-phase CEUS, 22/23 lesions (96%)
      were markedly hypoechoic. CT showed that the lesions were hypovascular in the
      arterial phase in 15/23 cases (66%) and hypervascular in 7/23 (30%) cases; one
      lesion (1/23; 4%) was isovascular. On delayed-phase CT, lesions were hyperdense
      in 17/23 cases (74%), hypodense in 5/23 (22%) cases and isodense in 1/23 (43%)
      cases. CONCLUSIONS: Enhancement discrepancy between delayed-phase CEUS
      (hypoechogenicity) and CT (hyperdensity) is common semiological findings in the
      study of IPCC.

PMID- 18338130
TI  - Hepatic radiofrequency under CT-fluoroscopy guidance.
AB  - PURPOSE: This study was done to assess the effectiveness and advantages of
      computed tomography (CT) fluoroscopy as a guide for locating and treating lesions
      that are not amenable to ultrasound (US) guidance, and to evaluate the CT signs
      of immediate technical success and the short-term results. MATERIALS AND METHODS:
      Over the past year, we selected 14 patients (four women and ten men; mean age 73,
      range 61-83 years) out of 103 candidates for hepatic radiofrequency ablation
      (RFA). The 14 lesions comprised seven residual tumours after combined
      embolisation and US-guided RFA of a large hepatocellular carcinoma (HCC), which
      were indistinguishable from necrosis or surrounding healthy parenchyma; two HCC
      nodules in locations that were inaccessible by US; five metastases (two from
      renal carcinoma, two from colorectal adenocarcinoma and one from lung carcinoma),
      of which one could not be distinguished from the surrounding healthy parenchyma
      on US and four were inaccessible by US. Lesion diameters were between 1.4 and 3.5
      cm. The procedures were performed in the CT room with anaesthesiological
      assistance using a coaxial LeVeen needle electrode (14 gauge, 2-to 4-cm array
      diameter). Immediate technical success was evaluated by multidetector CT (MDCT),
      and follow-up was carried out with MDCT at 3 and 6 months and yearly thereafter.
      RESULTS: Immediate technical success was obtained in 13/14 patients; one case
      required further placement of the electrode due to incomplete ablation of a
      hypervascular lesion. In 2/3 metastatic lesions with portal vein supply, there
      were no recurrences at 3 and 6 months; in 1/3, we observed disease progression,
      with the appearance of additional nodules at 6 months. The two metastases with
      arterial supply showed no signs of recurrence at 3 months; one case developed a
      recurrence along the ablation margin, with the appearance of satellite nodules at
      6 months. In two HCC nodules, there was immediate technical success and no
      recurrence at 3 and 6 months. Of the seven residual tumours of HCC, all treated
      with immediate technical success, we observed disease progression, with the
      appearance of satellite nodules at 3 months in one case, at 6 months in another
      and at 12 months in another; 3/7 patients were free of disease at 12-month follow
      up; 1/7 died 5 months later due to causes unrelated to the procedure.
      CONCLUSIONS: CT fluoroscopy is overcoming the limitations of CT in locating and
      treating lesions with different hepatic vascularisation and those unamenable to
      US; furthermore, it reduces the length of the procedure, thanks to the faster and
      more accurate placement of the needle electrode. MDCT proved to be a reliable
      method in the assessment of immediate and short-term results of RFA.

PMID- 18338131
TI  - Percutaneous vertebroplasty: the follow-up.
AB  - PURPOSE: This article reports on our experience treating vertebral fractures with
      percutaneous vertebroplasty. A clinical and imaging follow-up designed to
      identify the early (especially pulmonary embolism of bone cement) and late
      complications of the technique is proposed. MATERIAL AND METHODS: On the basis of
      the current guidelines, 101 patients were selected: 64 osteoporotic and 37
      neoplastic. A total of 173 vertebrae were treated. Procedures were performed with
      both computed tomography and fluoroscopic guidance. Residual pain was evaluated
      with a visual analogue scale score immediately after vertebroplasty and 1, 15,
      30, 90, 180 and 270 days later. Spine and chest radiographs were obtained 24 h
      after vertebroplasty; spine radiography was repeated 30 days later. RESULTS:
      Therapeutic success was obtained in 88% of osteoporotic patients and in 84% of
      neoplastic patients. Pulmonary cement emboli were identified in four patients,
      all of whom were asymptomatic. CONCLUSIONS: Percutaneous vertebroplasty is a safe
      and effective technique for the treatment of osteoporotic and neoplastic
      vertebral fractures. Clinical and imaging followup allows effective patient
      monitoring and early detection of possible complications.

PMID- 18338132
TI  - CT-guided percutaneous vertebroplasty: personal experience in the treatment of
      osteoporotic fractures and dorsolumbar metastases.
AB  - PURPOSE: This study was performed to evaluate the results and complications of
      percutaneous vertebroplasty (PVP) performed under CT guidance. MATERIALS AND
      METHODS: We treated 106 patients (182 PVP): 67 for osteoporotic vertebral
      compression fracture, and 39 for osteolytic metastases. The first 78 patients
      were treated using computed tomography (CT) combined with conventional
      fluoroscopy as an imaging guide (135 PVP). In 28 patients, the procedure was
      performed with multislice CT fluoroscopy (47 PVP). RESULTS: Partial or complete
      pain relief was obtained in 98% of patients within 24 h from the treatment;
      significant results were also obtained with regard to improvement in functional
      mobility and reduction of analgesic use. CT allowed the detection of cement
      leakage in 43.9%. Severe complications were one case of pneumothorax and two
      cases of symptomatic cement leakage. Mild complications included two cases of
      cement pulmonary embolism. During the follow-up, eight osteoporotic patients
      presented a new vertebral fracture, and new vertebral metastases appeared in two
      oncological patients. CONCLUSIONS: Our personal experience confirms the efficacy
      of PVP treatment for both osteoporotic and oncological patients. The use of CT
      guidance reduces the risk of complications in comparison with conventional
      fluoroscopy alone, as well as facilitates the detection of small cement leakages.

PMID- 18338133
TI  - Role of perfusion-weighted imaging at 3 Tesla in the assessment of malignancy of
      cerebral gliomas.
AB  - PURPOSE: This study was performed to clarify the role of perfusion-weighted
      imaging (PWI) at 3 Tesla in the characterisation of haemodynamic heterogeneity
      within gliomas and surrounding tissues and in the differentiation of high-grade
      from low-grade gliomas. MATERIALS AND METHODS: We examined 36 patients with
      histologically verified gliomas (25 with high-grade and 11 with low-grade
      gliomas). PWI was performed by first-pass gadopentetate dimeglumine T2*-weighted
      echo-planar images, and cerebral blood volume (CBV) maps were computed with a
      nondiffusible tracer model. Relative CBV (rCBV) was calculated by dividing CBV in
      pathological areas by that in contralateral white matter. RESULTS: In high-grade
      gliomas, rCBV were markedly increased in mass [mean+/-standard deviation (SD),
      4.3+/-1.2] and margins (4.0+/-1.1) and reduced in necrotic areas (0.3+/-0.3).
      Oedematous-appearing areas were divided in two groups according to signal
      intensity on T2-weighted images: tumour with lower (nearly isointense to grey
      matter) and oedema with higher (scarcely isointense to cerebrospinal fluid)
      signal intensity. Tumour showed significantly higher rCBV than did oedema (1.8+/
      0.5 vs. 0.5+/-0.2; p<0.001) areas. In low-grade gliomas, mass (2.0+/-1.5) and
      margin (2.2+/-1.2) rCBV were significantly lower than in high-grade gliomas
      (p<0.001). CONCLUSIONS: Three-Tesla PWI helps to distinguish necrosis from tumour
      mass, infiltrating tumour from oedema and high-grade from low-grade gliomas. It
      enhances the magnetic resonance (MR) assessment of cerebral gliomas and provides
      useful information for planning surgical and radiation treatment.

PMID- 18338134
TI  - E-learning tools for education: regulatory aspects, current applications in
      radiology and future prospects.
AB  - PURPOSE: E-learning, an abbreviation of electronic learning, indicates the
      provision of education and training on the Internet or the World Wide Web. The
      impact of networks and the Internet on radiology is undoubtedly important, as it
      is for medicine as a whole. The Internet offers numerous advantages compared with
      other mass media: it provides access to a large amount of information previously
      known only to individual specialists; it is flexible, permitting the use of
      images or video; and it allows linking to Web sites on a specific subject, thus
      contributing to further expand knowledge. Our purpose is to illustrate the
      regulatory aspects (including Internet copyright laws), current radiological
      applications and future prospects of e-learning. Our experience with the
      installation of an e-learning platform is also presented. MATERIALS AND METHODS:
      We performed a PubMed search on the published literature (without time limits)
      dealing with e-learning tools and applications in the health sector with specific
      reference to radiology. The search included all study types in the English
      language with the following key words: e-learning, education, teaching, online
      exam, radiology and radiologists. The Fiaso study was referred to for the
      regulatory aspects of e-learning. RESULTS: The application of e-learning to
      radiology requires the development of a model that involves selecting and
      creating e-learning platforms, creating and technologically adapting multimedia
      teaching modules, creating and managing a unified catalogue of teaching modules,
      planning training actions, defining training pathways and Continuing Education in
      Medicine (CME) credits, identifying levels of teaching and technological
      complexity of support tools, sharing an organisational and methodological model,
      training the trainers, operators' participation and relational devices, providing
      training, monitoring progress of the activities, and measuring the effectiveness
      of training. Since 2004, a platform--LiveLearning--has been used at our
      university: this is a Web-oriented application, that is, an Internet software
      solution that users can access through a Web browser. The pages displayed by the
      browser are dynamically generated through interaction with a database that
      collects both data required for the application to work and data related to the
      courses provided. There are different approaches to developing applications that
      use databases to store information. The selected approach is based on a modular
      three-level architecture divided into presentation level, intermediate level, and
      data level. The LiveLearning platform includes modules to manage multimedia
      contents and to interface with the streaming server so that the student can
      access the training contents directly from the platform interfaces. Furthermore,
      the platform offers its users different modules: Teaching Units, Documents,
      Forums, and Chats. By appropriately combining these modules, customised training
      can be devised based on specific requirements. CONCLUSIONS: The increasing
      diffusion of continuous education will reduce the costs of e-learning and make
      this training method, which helps keep pace with technological progress, more
      attractive, with significant professional gains for radiologists.

PMID- 18338135
TI  - Neonatal haemochromatosis associated with gastroschisis.
AB  - We describe, to our knowledge, the first case of progressive neonatal liver
      failure due to neonatal haemochromatosis (NH) occurring in an infant with a
      gastroschisis and review the literature regarding these two conditions. A 1,665 g
      male infant with antenatally diagnosed gastroschisis was born with a severe
      coagulopathy, anaemia, thrombocytopenia, hypoglycaemia and jaundice. He developed
      progressive liver failure, complicated by necrotising enterocolitis. Serum
      ferritin was elevated at 1,459 microg/L. He died on day 40 and a limited post
      mortem examination confirmed significant hepatic siderosis with fibrosis and
      cholestasis, and siderosis of the pancreas. Although no genetic aetiology for
      gastroschisis has been identified, an occasional inherited tendency has been
      observed. There is also evidence to support an autosomal recessive inheritance in
      NH.

PMID- 18338136
TI  - Bidens pilosa L. exhibits high sensitivity to coumarin in comparison with three
      other weed species.
AB  - Nine natural plant compounds were screened for phytotoxicity to Bidens pilosa L.
      a troublesome weed in field and plantation crops. The sensitivity of three other
      weed species to coumarin, the most active identified compound, was also
      evaluated. Coumarin, at a concentration of 500 microM, had little effect on
      germination and growth of Senna obtusifolia L., Euphorbia heterophylla L., and
      Ipomoea grandifolia L. when compared with its effects on B. pilosa L. In a
      concentration range of 10-100 microM, coumarin caused a dose-dependent inhibition
      of germination and growth of B. pilosa L. The measurements of some parameters of
      energy metabolism revealed that coumarin-treated root tissues exhibited
      characteristics of seedlings in an earlier stage of growth, including higher
      respiratory activity and higher activities of alcohol dehydrogenase and
      lipoxygenase. These results suggest that coumarin inhibition of germination and
      growth of B. pilosa L. was not a consequence of an impairment of energy
      metabolism. Rather, it seems to act as a cytostatic agent, retarding germination.
      At concentrations above 50 microM, coumarin increased lipoxygenase activity and
      the level of conjugated dienes of root extracts, suggesting that it may induce
      oxidative stress in seedling roots.

PMID- 18338137
TI  - [Thrombelastometric detection of factor XIII deficiency].
AB  - While undergoing Whipple's operation (pancreaticoduodenectomy) a patient
      developed diffuse bleeding and an unexpectedly high blood loss. An
      intraoperatively performed thrombelastometry with ROTEM (Pentapharm, Munich,
      Germany) showed an aprotonin-resistant mild fibrinolysis and suggested the
      presence of an isolated deficiency of coagulation factor XIII. This was confirmed
      by a second thrombelastometry, where no lysis was seen after in vitro
      substitution of factor XIII. After administration of 1250 IU factor XIII
      concentrate the diffuse bleeding ceased and further substitution of coagulation
      factor concentrates or fresh frozen plasma was not necessary. A postoperatively
      performed analysis confirmed the factor XIII deficiency (52%).

PMID- 18338139
TI  - [Relaxometry for antiemetic prophylaxis?].

PMID- 18338138
TI  - [Reduction in no flow time using a laryngeal tube: comparison to bag-mask
      ventilation].
AB  - OBJECTIVE: In 2005 the European Resuscitation Council (ERC) published the new
      guidelines for Advanced Life Support (ALS). One of the aims was to reduce the no
      flow time (NFT), without chest compression in the first period of cardiac arrest.
      Furthermore the guidelines recommend that endotracheal intubation should only be
      carried out by personnel experienced in this procedure. METHODS: An attempt was
      made to evaluate whether the use of the laryngeal tube suction (LTS-D) for
      emergency airway management could contribute to reduce NFT compared to bag-mask
      ventilation (BMV). In a randomised prospective study 50 participants were asked
      to perform standardised simulated cardiac arrest management on a full-scale
      simulator following a one-day cardiac arrest training. Each participant was
      randomised into the LTS-D and the BMV group for airway management. At the end of
      each scenario an evaluation of the use of each ventilation procedure by the
      participants was made by means of a questionnaire. RESULTS: During the manikin
      scenario (430 s for LTS-D and 420 s for BMV) there was a significant difference
      in the overall NFT comparing the use of the LTS-D vs. BMV (105.8 s, range 94-124
      s vs. 150.7 s, range 124-179 s; p<0.01). This corresponded during the whole
      scenario to a proportion of 24.6% (LTS-D) or 35.9% (BMV). Using the LTS-D all
      participants were able to ventilate the manikin successfully (tidal volume 500
      600 ml). In a subjective evaluation of the different airway management procedures
      by the participants more than 90% expressed a positive opinion about the LTS-D
      with respect to ease of insertion and safety of ventilation. CONCLUSION: The use
      of the LTS-D on a manikin by emergency physicians after standardised cardiac
      arrest training significantly reduces the NFT in comparison to BMV. Therefore the
      LTS-D seems to be a good alternative to BMV during a simulated cardiac arrest
      scenario.

PMID- 18338140
TI  - [Photodynamic therapy of granuloma annulare].

PMID- 18338141
TI  - [Multimodal treatment of pyoderma gangrenosum].

PMID- 18338142
TI  - [Acne inversa with arm plexus involvement].

PMID- 18338143
TI  - [Classical Kaposi's sarcoma in a 78-year-old woman].

PMID- 18338144
TI  - [Atopic dermatitis. Psychosomatic and psychotherapeutic treatment].
AB  - Patients with chronic relapsing atopic dermatitis often suffer from stress
      related exacerbations, exhaustion, depression, anxiety and helplessness. They
      then may feel they cannot influence the course of their disease, and often
      develop problems in social interaction. These case reports focus on the different
      possibilities in addition to classical dermatologic therapy--empathic
      psychosomatic-orientated conversations, strategies of behavioral medicine and the
      effect of long-term psychodynamic psychotherapy.

PMID- 18338145
TI  - [Borderline personality disorder in dermatology].
AB  - Borderline personality disorder is a syndrome of complex psychopathology which is
      not very common in dermatology. The emotional symptoms are broad and variable,
      but typically feature emotional instability, intense anger or lack of control of
      anger, impulsiveness, instabilities in self-perception, problems at work, chronic
      feelings of emptiness, unstable partnership relations and recurrent suicidal
      threats. Self-inflicted injuries are common and may lead patients to
      dermatologists. A 26-year old woman with borderline personality was hospitalized
      for neurosyphilis. During inpatient treatment she repeatedly cut herself with
      razor blades. This article highlights the diagnostic criteria and differential
      approach of the borderline personality disorder in order to facilitate early
      recognition and therapy.

PMID- 18338146
TI  - [Suicidal behavior in dermatology].
AB  - Even in dermatology one can potentially encounter suicidal patients. A risk of
      suicide can be preexisting, appear as complication of skin disorders or be
      triggered by medications such as interferons. Patients at risk must be
      specifically asked about suicidal ideations and tendencies. Acute suicide risk
      requires immediate crisis intervention. In dermatology suicide risk has been
      described in severe acne conglobata (especially men) and metastatic melanoma.
      Patients with chronic or potentially fatal disease or severe pain may be
      suicidal. In addition patients with depression, alcohol dependency, substance
      abuse, schizophrenia or borderline personality disorder are at special risk. We
      review psychodermatological diseases with risk of suicide and point out treatment
      strategies. More attention should be focused on the early recognition of a
      possible risk of suicide in dermatology patients.

PMID- 18338147
TI  - [Pathogenesis and treatment of presbyacusis. Current status and future
      perspectives].
AB  - Factors responsible for presbyacusis include physiological ageing processes as
      well as endogenous or exogenous causes. In the industrial countries, two main
      exogenous causes are exposure to loud noise and obesity. Pathomechanisms
      contributing to presbyacusis are hypoxia/ischemia, reactive species formation and
      oxidative stress, apoptotic and necrotic death of hair cells and spiral ganglion
      cells as well as inherited and acquired mutations in the mitochondrial DNA.
      Important for the successful treatment of presbyacusis is a timely fitting of
      hearing aids on both ears to improve communication and provide the auditory
      system with acoustic information. Using the hearing aids will also elevate the
      detection threshold of an existing tinnitus signal. At present, several
      therapeutic strategies based on pharmacological intervention are under
      discussion. The application of antioxidants or caloric restriction are considered
      to prevent or reduce oxidative stress-induced damage. Animal experiments
      evidenced that superoxide dismutase 2 (SOD2) strongly decreases in age; thus, a
      further approach may be the overexpression or modulation of the SOD2 within the
      cochlea. Adenoviral-mediated gene transfer technology would be a tempting
      approach to address this type of therapy. Finally, hair cell regeneration could
      be a possible treatment of presbyacusis in the future.

PMID- 18338148
TI  - [Sudden swelling in the right supraclavicular region].

PMID- 18338149
TI  - Do native brown trout and non-native brook trout interact reproductively?
AB  - Reproductive interactions between native and non-native species of fish have
      received little attention compared to other types of interactions such as
      predation or competition for food and habitat. We studied the reproductive
      interactions between non-native brook trout (Salvelinus fontinalis) and native
      brown trout (Salmo trutta) in a Pyrenees Mountain stream (SW France). We found
      evidence of significant interspecific interactions owing to consistent spatial
      and temporal overlap in redd localizations and spawning periods. We observed
      mixed spawning groups composed of the two species, interspecific subordinate
      males, and presence of natural hybrids (tiger trout). These reproductive
      interactions could be detrimental to the reproduction success of both species.
      Our study shows that non-native species might have detrimental effects on native
      species via subtle hybridization behavior.

PMID- 18338150
TI  - An upper Cretaceous lizard with a lower temporal arcade.
AB  - The reduced lower temporal arcade of the skull and the movable quadrate are the
      most distinctive features of squamates. Up to now, no exception has been
      documented for any fossil or extant squamates. We report here a new fossil lizard
      that possesses a complete lower temporal arcade and an unmovable quadrate. The
      anatomical relationships indicate that those two modifications were secondarily
      obtained in the new lizard. The complete lower temporal bar and the firm contact
      between the pterygoid and quadrate may have served as a brace to support the
      quadrate jaw articulation and thus prevent it from twisting anteriorly rather
      than posteriorly during the bite cycles. This represents an entirely new pattern
      of jaw muscle functions within the Squamata.

PMID- 18338151
TI  - [15th annual congress of the working group for kidney transplantation of the
      academy of German urologists: Jena, 15th-17th november 2007].

PMID- 18338152
TI  - [Transurethral enucleation of the prostate with the holmium: YAG laser system:
      how much power is necessary?].
AB  - PURPOSE: To evaluate the efficacy and safety of an intermediate power (50 W)
      holmium:YAG laser system for transurethral enucleation of the prostate (TULP)
      with the use of a new mechanical morcellator. Our results are compared with the
      results of high-powered holmium laser enucleation (HoLEP) presented in the
      literature. MATERIAL AND METHODS: From December 2003 to January 2008, 129
      patients with benign prostatic hyperplasia were treated by TULP. In 45 cases
      (group A; 2.0, 12 Hz) we used a bipolar resectoscope (VISTA/ACMI) for
      morcellation, whereas after that morcellation was accomplished with a modified
      endoscopic shaver (Wolf). Thirty-nine patients were treated using 25 W (group B;
      2.0 J, 12 Hz), and 45 patients were treated using 40 W (group C; 2.2 J 18 Hz),
      who were compared with 45 matched-pair patients who received transurethral
      resection of the prostate (TURP; group D). Finally, the literature on HoLEP was
      reviewed. RESULTS: Bipolar morcellation significantly prolonged the operating
      time (135 vs. 131 vs. 96 min). The morcellation speed averaged 2.8 (range 1.3
      5.2) g/min with no complications. The resection speed (retrieval rate) of 40-W
      TULP was comparable to that for TURP (0.71 vs. 0.76 g/min). The transfusion rate
      was lower than for TURP (8% vs. 12%), with a smaller Hb difference (3.1 vs. 3.8
      mg/dl). Catheter times (3.4 vs. 4.1 days) were similar; however, hospital stay
      was significantly shorter after TULP (5.2 vs. 6.8 days). The complication rate
      was significantly lower (6.6% vs. 13.3%). The efficacy of HoLEP significantly
      improved with introduction of the morcellator: Resection speed increased from
      0.34-0.61 g/min to 0.48-0.82 g/min. HoLEP was better than 40-W TULP regarding
      transfusion rate (0-4% vs. 8%) and catheter time (1.1-1.5 vs. 3.4 days).
      Complications and functional results were similar. CONCLUSION[UBERSCHRIFT]: The
      intermediate-power 50-W holmium laser together with the new morcellator enable
      safe transurethral enucleation of the prostate. As with HoLEP, the procedure has
      a significant learning curve. The retrieval times of TULP are similar to those
      for HoLEP, but the risk of bleeding is higher. New modifications (i.e., thullium
      laser) will further improve the technique of laser enucleation.

PMID- 18338153
TI  - [Robot-assisted laparoscopic radical prostatectomy].
AB  - The advantage of minimally invasive surgery in the form of laproscopic radical
      prostatectomy compared with open retropubic radical prostatectomy is
      indisputable. But a long learning curve seems to be a clear disadvantage. Robotic
      surgery devices such as the da Vinci system could be very helpful here. The aim
      of this study was to demonstrate our own experience with da Vinci prostatectomy
      in consideration of the learning curve. Since implementation of the da Vinci
      system 23 months ago, we have done over 300 operating procedures with the system.
      Despite of having great know how in laparoscopic surgery the conversion rate was
      only 1.7%. The oncological outcome was satisfactory and comparable with the
      results reported in the literature. A complication rate of only 5.1% also seems
      acceptable. With the da Vinci system, we can combine the advantages of a
      minimally invasive procedure with those of open surgery but without the
      disadvantage of a long learning curve. At the moment, the expense factor remains
      a handicap.

PMID- 18338154
TI  - AB-QTL analysis in winter wheat: II. Genetic analysis of seedling and field
      resistance against leaf rust in a wheat advanced backcross population.
AB  - The present study aimed to localize exotic quantitative trait locus (QTL) alleles
      for the improvement of leaf rust (P. triticina) resistance in an advanced
      backcross (AB) population, B22, which is derived from a cross between the winter
      wheat cultivar Batis (Triticum aestivum) and the synthetic wheat accession
      Syn022L. The latter was developed from hybridization of T. turgidum ssp.
      dicoccoides and T. tauschii. Altogether, 250 BC2F3 lines of B22 were assessed for
      seedling resistance against the leaf rust isolate 77WxR under controlled
      conditions. In addition, field resistance against leaf rust was evaluated by
      assessing symptom severity under natural infestation across multiple
      environments. Simultaneously, population B22 was genotyped with a total of 97 SSR
      markers, distributed over the wheat A, B and D genomes. The phenotype and
      genotype data were subjected to QTL analysis by applying a 3-factorial mixed
      model analysis of variance including the marker genotype as a fixed effect and
      the environments, the lines and the marker by environment interactions as random
      effects. The QTL analysis revealed six putative QTLs for seedling resistance and
      seven for field resistance. For seedling resistance, the effects of exotic QTL
      alleles improved resistance at all detected loci. The maximum decrease of disease
      symptoms (-46.3%) was associated with marker locus Xbarc149 on chromosome 1D. For
      field resistance, two loci had stable main effects across environments and five
      loci exhibited marker by environment interaction effects. The strongest effects
      were detected at marker locus Xbarc149 on chromosome 1D, at which the exotic
      allele decreased seedling symptoms by 46.3% and field symptoms by 43.6%,
      respectively. Some of the detected QTLs co-localized with known resistance genes,
      while others appear to be as novel resistance loci. Our findings indicate, that
      the exotic wheat accession Syn022L may be useful for the improvement of leaf rust
      resistance in cultivated wheat.

PMID- 18338155
TI  - Cotton (Gossypium spp.) R2R3-MYB transcription factors SNP identification,
      phylogenomic characterization, chromosome localization, and linkage mapping.
AB  - R2R3-MYB transcription factors of plants are involved in the regulation of
      trichome length and density. Several of them are differentially expressed during
      initiation and elongation of cotton fibers. We report sequence phylogenomic
      characterization of the six MYB genes, their chromosomal localization, and
      linkage mapping via SNP marker in AD-genome cotton (2n = 52). Phylogenetic
      grouping and comparison to At- and Dt-genome putative ancestral diploid species
      of allotetraploid cotton facilitated differentiation between genome-specific
      polymorphisms (GSPs) and marker-suitable locus-specific polymorphisms (LSPs). The
      SNP frequency averaged one per 77 bases overall, and one per 106 and 30 bases in
      coding and non-coding regions, respectively. SNP-based multivariate relationships
      conformed to independent evolution of the six MYB homoeologous loci in the four
      tetraploid species. Nucleotide diversity analysis indicated that the six MYB loci
      evolved more quickly in the Dt- than At-genome. The greater variation in the Dt-D
      genome comparisons than that in At-A genome comparisons showed no significant
      bias among synonymous substitution, non-synonymous substitution, and nucleotide
      change in non-coding regions. SNPs were concordantly mapped by deletion analysis
      and linkage mapping, which confirmed their value as candidate gene markers and
      indicated the reliability of the SNP discovery strategy in tetraploid cotton
      species. We consider that these SNPs may be useful for genetic dissection of
      economically important fiber and yield traits because of the role of these genes
      in fiber development.

PMID- 18338156
TI  - [Spinal surgery in the elderly: does age have an influence on the complication
      rate?].
AB  - In accordance with the demographic trend, the number of elderly patients with
      spinal diseases which require surgery will increase continuously. Up to now, age
      has often been regarded as a contraindication for an elective operation. However,
      a review of the existing literature, the results of the European spine register
      "Spine Tango" and our own results show that the rate of complications after
      minimally invasive spinal surgery is as low in the elderly as it is in the
      younger population. But the higher the complexity of surgery, the higher the rate
      of complications with increasing age. However, even elderly (>65 years) and very
      elderly (>80 years) patients seem to benefit from surgical treatment, independent
      of the extent of spinal surgery. Because chronic pain leads to physical
      limitations, an impaired quality of life as well as a declined state of health,
      and because surgery can significantly improve these factors, even while remaining
      aware of the operational risks, age itself should not be considered as a
      contraindication for spinal surgery.

PMID- 18338157
TI  - Age-dependent differences in nicotine reward and withdrawal in female mice.
AB  - RATIONALE: Adolescent smoking is an increasing epidemic in the US. Research has
      shown that the commencement of smoking at a young age increases addiction and
      decreases the probability of successful cessation; however, limited work has
      focused on nicotine dependence in the female. OBJECTIVE: The goal of the present
      study was to identify the biological and behavioral factors that may contribute
      to nicotine's increased abuse liability in female adolescents using animal models
      of nicotine dependence. MATERIALS AND METHODS: Early adolescent (PND 28) and
      adult (PND 70) female mice were compared in various aspects of nicotine
      dependence using reward and withdrawal models following sub-chronic nicotine
      exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were
      examined. RESULTS: In the conditioned place preference model, adolescents
      demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in
      adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit
      rewarding effects. Furthermore, adolescents displayed increased physical, but not
      affective, withdrawal signs in three models. Upon acute exposure to nicotine,
      adolescent mice showed increased sensitivity in an analgesic measure as well as
      hypothermia. After chronic nicotine exposure, both adults and adolescents
      displayed tolerance to nicotine with adolescents having a lower degree of
      tolerance to changes in body temperature. CONCLUSIONS: These data indicate that
      differences in nicotine's rewarding and aversive effects may contribute to
      variations in certain components of nicotine dependence between adult and
      adolescent female mice. Furthermore, this implies that smoking cessation
      therapies may not be equally effective across all ages.

PMID- 18338158
TI  - The effects of nicotine on the attentional modification of the acoustic startle
      response in nonsmokers.
AB  - RATIONALE AND OBJECTIVE: Research on nicotine and attention has mainly utilized
      samples of deprived smokers and tasks requiring volitional responses, raising the
      question of whether nicotine improves attention or simply alleviates withdrawal
      or improves motor speed. This study used the startle eyeblink reflex to assess
      nicotine effects on auditory attention in nonsmokers. MATERIALS AND METHODS:
      Sixty-seven healthy young adult nonsmokers completed a tone discrimination task.
      Acoustic startle probes were presented 60, 120, 240, or 4,500 ms after the onset
      of two-thirds of the tones and during intertrial intervals. Attention was
      assessed via (1) short-lead prepulse inhibition (PPI) of startle, a measure of
      early filtering; (2) long-lead prepulse facilitation (PPF) of startle, a measure
      of sustained processing; and (3) the modification of PPI and PPF by focused
      attention. Participants completed two laboratory sessions, once while wearing a 7
      mg transdermal nicotine patch and once while wearing a placebo patch. Patches
      were administered in a double-blind procedure. RESULTS: Nicotine increased
      overall PPI, eta2(p)=0.09. Attention increased long-lead PPF, eta2(p)=0.25, but
      not short-lead PPI. Nicotine did not reliably enhance early or late controlled
      attentional processing in the sample overall. However, correlational analyses
      demonstrated that nicotine most improved attentional modification of short-lead
      PPI among participants with the weakest early attentional processing under
      placebo conditions. CONCLUSIONS: Nicotine enhanced early attentional filtering in
      general, and the effects of nicotine on early focused attention were dependent
      upon individual differences in placebo levels of attentional processing. The
      present data suggest that the effects of nicotine on attention extend beyond the
      alleviation of withdrawal and simple motor speeding.

PMID- 18338159
TI  - Characterization of selected organic compound classes in secondary organic
      aerosol from biogenic VOCs by HPLC/MSn.
AB  - The formation of secondary organic aerosols (SOA) has been investigated
      intensively during the last two decades in numerous field and laboratory studies
      and a general understanding exists about the major particle-phase products.
      However, recent studies show that several new product classes, such as esters,
      peroxides or organosulfates, also have to be considered in order to understand
      the detailed chemical mechanisms leading to SOA as well as to predict the aerosol
      mass loadings. For the identification and quantification of these three compound
      classes as well as for carboxylic SOA compounds, liquid chromatography (LC)/mass
      spectrometry (MS) is the most appropriate analytical method. In this article we
      try to summarize briefly the work that has been done for the determination of SOA
      related carboxylic acids and we present new LC/tandem MS results on the
      characterization of esters, peroxides and organosulfates. In contrast to earlier
      work, the mass-spectrometric characterization of the individual compounds is
      always based on the comparison with authentic reference compounds.

PMID- 18338160
TI  - Application of temperature-controlled micro planar chromatography for separation
      and quantification of testosterone and its derivatives.
AB  - Temperature-controlled micro thin-layer chromatography (TLC) was applied for
      separation and quantification studies of testosterone and its derivatives
      including methyltestosterone, testosterone propionate, isobutyrate,
      phenylpropionate, isocaproate, enanthate and caprate. Chromatographic studies
      were performed on silica-, octadecylsilica- and aluminum-coated plates working
      inside a small thermostated horizontal chamber unit allowing one-dimensional and
      two-dimensional developing modes with an elution distance of 45 mm. Retention
      properties of steroids were investigated across a whole range of binary mixtures
      such as methanol/water, acetonitrile/water, methanol/dichloromethane and
      acetone/hexane (0-100% v/v). Moreover, the effect of temperature ranging from -20
      to +60 degrees C under saturated and unsaturated chamber conditions was also
      investigated. Our results revealed that depending on the mobile phase polarity
      the separation system based on the low carbon load wettable with water RP18W
      plates may work as a normal-phase (NP) or reversed-phase (RP) chromatographic
      system. It has been also demonstrated that micro TLC equipment can be applied as
      a fast retention screening device as well as simple and robust quantitative tool
      for determination of testosterone residue containing testosterone derivatives in
      complex samples.

PMID- 18338161
TI  - Should medical students learn to develop a personal formulary? An international,
      multicentre, randomised controlled study.
AB  - OBJECTIVE: This study was performed to determine whether students who are trained
      in developing a personal formulary become more competent in rational prescribing
      than students who have only learned to use existing formularies. METHODS: This
      was a multicentre, randomised, controlled study conducted in eight universities
      in India, Indonesia, the Netherlands, the Russian Federation, Slovakia, South
      Africa, Spain and Yemen. Five hundred and eighty-three medical students were
      randomised into three groups: the personal formulary group (PF; 94), the existing
      formulary group (EF; 98) and the control group (C; 191). The PF group was taught
      how to develop and use a personal formulary, whereas e the EF group was taught
      how to review and use an existing formulary. The C group received no additional
      training and participated only in the tests. Student's prescribing skills were
      measured by scoring their treatment plans for written patient cases. RESULTS: The
      mean PF group score increased by 23% compared with 19% for the EF group (p <
      0.05) and 6% for controls (p < 0.05). The positive effect of PF training was only
      significant in universities that had a mainly classic curriculum. CONCLUSION:
      Training in development and use of a personal formulary was particularly
      effective in universities with a classic curriculum and with traditional
      pharmacology teaching. In universities with a general problem-based curriculum,
      pharmacotherapy teaching can be based on either existing or personal formularies.

PMID- 18338162
TI  - An unusual form of spondyloepiphyseal dysplasia, with advanced carpal and spinal
      end-plate ossification mimicking COMP-mutation-like multiple epiphyseal
      dysplasia.
AB  - We present a child with irregular ossification of tubular bone epiphyses, short
      bones, and spine. The radiographic evolution of bones undergoing endochondral
      ossification was followed from the age of 1 year 9 months to 6 years. The unusual
      features demonstrated in this child made classification difficult:
      pseudoachondroplasia was excluded because no mutations of the COMP gene were
      found. Considering the evolution of the radiographic appearances, the most likely
      diagnosis would seem to be an unusual form of spondyloepiphyseal dysplasia,
      mimicking some aspects of multiple epiphyseal dysplasia. Endochondral
      ossification was diffusely altered with a mixture of epiphyseal ossification
      delay associated with acceleration and early fusion. This case was a unique
      presentation within the family, suggesting a mutation in the affected child.

PMID- 18338163
TI  - Aggressive angiomyxoma of the thigh.
AB  - Aggressive angiomyxoma is a rare tumour that typically occurs in the perineum in
      women of reproductive age. A small number of cases occurring in men have been
      reported, all of which were located in the low pelvis, perineum or scrotum. While
      benign, the tumour is locally infiltrative and consequently has a high rate of
      local recurrence following surgery; therefore, accurate pre-operative diagnosis
      is important. The characteristic location of these tumours in the low pelvis or
      perineum has led to speculation that aggressive angiomyxomas arise from a
      mesenchymal cell that is unique to the perineum. We describe a case of aggressive
      angiomyxoma arising in the thigh of a 54-year-old man, which we believe is the
      first reported instance of this rare neoplasm occurring remote from the pelvis or
      perineum in a male patient. Cross-sectional imaging demonstrated a well-defined
      mass that had low density on CT and high intensity on fluid-sensitive MR
      sequences. Biopsy was non-diagnostic and excision was performed. At histological
      analysis, the tumour exhibited the characteristic features of aggressive
      angiomyxoma, with bland spindle cells and large, hyalinised blood vessels in a
      hypocellular myxoid matrix. Extensive immunohistochemical staining further
      supported the diagnosis. While the imaging features of these tumours are non
      specific and suggestive of myxoid neoplasms, the diagnosis should be considered
      whenever biopsy of a myxoid-appearing mass yields hypocellular, non-diagnostic
      material, despite adequate sampling.

PMID- 18338164
TI  - Role of [18F]FDG-PET/CT after radiofrequency ablation of liver metastases:
      preliminary results.
AB  - PURPOSE: Focal metastasis may be treated with radiofrequency ablation (RFA), a
      low invasive method yet limited by the lack of direct evidence of radicality of
      treatment. We, hereby, aimed at assessing the role of positron emission
      tomography-computed tomography (PET/CT) with fluoride radiolabeled deoxy-glucose
      ([(18)F]FDG) in RFA treatment success evaluation and early diagnosis of local
      relapse of liver metastasis after RFA procedure. METHODS: RFA was performed in
      nine patients on 12 liver metastasis, serially imaged through [(18)F]FDG-PET/CT
      and multidetector CT (MDCT) at 1, 3, 6, and 9 months after treatment. Eight
      lesions were also scanned with [(18)F]FDG-PET/CT at 1 week after treatment.
      Imaging analyses were performed on 47 [(18)F]FDG-PET/CT and 51 MDCT. Imaging
      reading outcomes were compared to each other and to biopsy tissue results when
      available. RESULTS: In one case, [(18)F]FDG-PET/CT revealed radiotracer uptake at
      RFA site a week after procedure. Negative concordant outcome was obtained on
      eight lesions at 1 month after RFA, on eight cases at 3 months, on four at 6
      months, and on two cases at 9 months. Extra-liver (peritoneal) disease was
      detected in one case by both [(18)F]FDG-PET/CT and MDCT. In seven cases,
      [(18)F]FDG-PET/CT revealed the presence of local recurrence earlier than MDCT. In
      no cases did MDCT detect local relapse earlier than [(18)F]FDG-PET/CT.
      CONCLUSION: [(18)F]FDG-PET/CT may detect RFA treatment failure as well as local
      relapse after RFA earlier than MDCT.

PMID- 18338165
TI  - Something old, something new, PET in adrenal imaging.

PMID- 18338166
TI  - Could 99mTc-glucarate be used to evaluate tumour necrosis? In vitro and in vivo
      studies in leukaemic tumour cell line U937.
AB  - PURPOSE: The aim of this study was to determine whether (99m)Tc-glucarate
      ((99m)Tc-GLA) is a powerful and discriminant tumour necrosis marker. MATERIALS
      AND METHODS: The induction of apoptosis and secondary necrosis (by a
      chemotherapeutic agent) and necrosis (by intense hyperthermia) was studied on an
      in vitro and in vivo leukaemic cell line model (U937). The percentage of
      apoptosis/necrosis in vitro was determined by flow cytometry after staining cells
      with annexin-V-fluorescein/propidium iodide. The uptake of (99m)Tc-GLA was
      studied after treatments that produce an optimal of necrosis cells or apoptotic
      cells. Three populations of interest: viable, apoptotic and necrotic cells were
      sorted by flow cytometry. The uptake and the intracellular distribution of
      (99m)Tc-GLA on each population have been studied. We also investigated the
      influence of necrosis on (99m)Tc-GLA uptake in a model of U937 xenografts in nude
      mice. RESULTS: The accumulation of (99m)Tc-GLA in untreated and apoptotic cells
      was lower than in necrotic cells. Cell sorting discriminated each cellular
      population and showed a 14% accumulation in necrotic cells and no more than a 3%
      in apoptotic cells. In apoptotic and viable cells, (99m)Tc-GLA is distributed
      between the cytosolic/membrane and the nucleus fractions. In necrotic cells,
      (99m)Tc-GLA is mainly found in the nucleus fraction. In vivo investigations
      showed a higher (99m)Tc-GLA uptake in necrotic tumour than in apoptotic and
      control ones. CONCLUSIONS: (99m)Tc-GLA may be a useful agent to specifically
      evaluate tumour necrosis and may be helpful for the follow-up of patients with
      cancer.

PMID- 18338167
TI  - PET imaging with 11C-acetate in prostate cancer: a biochemical, radiochemical and
      clinical perspective.
AB  - PURPOSE: In the present study, the potential clinical role of 11C-acetate PET
      mainly in the differential diagnosis, in the staging and in the follow-up of
      prostate cancer patients is reported. METHODS: Each of the above points has been
      accurately investigated by studying the specific biochemical and radiobiochemical
      behaviour of this positron emitter compound. RESULTS AND CONCLUSION: The imaging
      quality of 11C-acetate PET and its unique mechanisms of cellular uptake, make
      such radiotracer a powerful tool in evaluating all the steps of the prostatic
      cancer.

PMID- 18338168
TI  - Langerhans' cell histiocytosis of the spine in children with soft tissue
      extension and chemotherapy.
AB  - The objectives of this paper were to look into the possible incidence of obvious
      soft tissue extension from Langerhans' cell histiocytosis (LCH) of the spine in
      children and to evaluate the effects of chemotherapy for those patients. Eighteen
      patients with histopathological diagnosis of LCH were reviewed and nine with
      obvious paravertebral soft tissue extension were included in this study. Soft
      tissue extension was involved in the spinal canal and/or around the vertebral
      body in eight cases and posterior involvement was prevalent in one case. Eight
      patients experienced neurological symptoms. All received chemotherapy and one had
      surgical treatment. The mean follow-up time was 30.3 months. Soft tissue
      extension disappeared completely in all patients. No clinical evidence of disease
      was observed at the most recent follow-up. The incidence of LCH of the spine in
      children with obvious soft tissue extension was up to 50%. Chemotherapy is safe
      and effective, and surgical decompression was probably not necessary for most
      patients.

PMID- 18338169
TI  - Simultaneous expression of Oct4 and genes of three germ layers in single cell
      derived multipotent adult progenitor cells.
AB  - Future application of adult stem cells in clinical therapies largely depends on
      the successful isolation of homogeneous stem cells with high plasticity.
      Multipotent adult progenitor cells (MAPCs) are thought to be a more primitive
      stem cell population capable of extensive in vitro proliferation with no
      senescence or loss of differentiation capability. The present study was aimed to
      find a less complicated and more economical protocol for obtaining single cell
      derived MAPCs and understand the molecule mechanism of multi-lineage
      differentiation of MAPCs. We successfully obtained a comparatively homogeneous
      population of MAPCs and confirmed that single cell-derived MAPCs were able to
      transcribe Oct4 and genes of three germ layers simultaneously, and differentiate
      into multiple lineages. Our observations suggest that single cell-derived MAPCs
      under appropriate circumstances could maintain not only characteristics of stem
      cells but multi-lineage differentiation potential through quantitative modulation
      of corresponding regulating gene expression, rather than switching on expression
      of specific genes.

PMID- 18338170
TI  - Role of (Glu --> Arg, Q5R) mutation of the intrinsic factor in pernicious anemia
      and other causes of low vitamin B12.

PMID- 18338171
TI  - Molecular predictors of human nervous system cancer responsiveness to enediyne
      chemotherapy.
AB  - PURPOSE: To identify and mathematically model molecular predictors of response to
      the enediyne chemotherapeutic agent, neocarzinostatin, in nervous system cancer
      cell lines. METHODS: Human neuroblastoma, breast cancer, glioma, and
      medulloblastoma cell lines were maintained in culture. Content of caspase-3 and
      Bcl-2, respectively, was determined relative to actin content for each cell line
      by Western blotting and optical densitometry. For each cell line, sensitivity to
      neocarzinostatin was determined. Brain tumor cell lines were stably transfected
      with human Bcl-2 cDNA cloned into the pcDNA3 plasmid vector. RESULTS: In human
      tumor cell lines of different tissue origins, sensitivity to neocarzinostatin is
      proportional to the product of the relative contents of Bcl-2 and caspase-3 (r
      (2) = 0.9; P < 0.01). Neuroblastoma and brain tumor cell lines are particularly
      sensitive to neocarzinostatin; the sensitivity of brain tumor lines to
      neocarzinostatin is enhanced by transfection with an expression construct for Bcl
      2 and is proportional in transfected cells to the product of the relative
      contents of Bcl-2 and caspase-3 (r (2) = 0.7). CONCLUSION: These studies
      underscore the potential of molecular profiling in identifying effective
      chemotherapeutic paradigms for cancer in general and tumors of the nervous system
      in particular.

PMID- 18338172
TI  - Antitumor activity of noscapine in human non-small cell lung cancer xenograft
      model.
AB  - PURPOSE: An antitussive plant alkaloid, Noscapine HCl (Nos) displays anticancer
      activity and has a safe pharmacological profile in humans. The current study was
      aimed to investigate the in vitro and in vivo anti tumor activity of Nos to
      determine possible mechanisms of anti tumor activity for treatment of non-small
      cell lung cancer (NSCLC). METHODS: In vitro cytotoxicity of Nos was studied in
      H460 cells treated with different doses of Nos (10-160 microM) for 72 h and cell
      viability was determined using crystal violet assay. Apoptosis in H460 cells was
      evaluated by TUNEL assay after treatment of cells for 72 h with 30 and 40 microM
      doses of Nos. For in vivo studies, female athymic Nu/nu mice were xenografted
      with H460 tumors and on day 4 onwards Nos was administered orally at dose of 300,
      450 and 550 mg/kg/day for 24 days. As a control, xenografted tumors were
      separately treated with Docetaxel (10 mg/kg i.v. bolus on day 5, 11, 17, 23). The
      tumor volumes were measured every five days. Expression of PARP, Bcl(2, )Bax, and
      caspase-3 families of proteins was measured by Western Blotting (WB), while TUNEL
      and Immunohistochemical methods were utilized to determine DNA fragmentation and
      cleaved caspase-3 levels respectively. RESULTS: Nos inhibited growth of H460
      cells with the IC50 values of 34.7 +/- 2.5 microM. Nos at 30 and 40 microM doses
      caused apoptosis as evidenced by nuclear condensation in treated H460 cells. Nos
      caused 49, 65 and 86% reduction in the xenografted tumor volumes at a dose of 300
      (P < 0.05), 450 (P < 0.01), 550 mg/kg/day (P < 0.01), respectively, when compared
      to controls. Nos-dependent suppression of xenografted tumor growth involved up
      regulation of PARP, Bax, caspase-3 and repression of Bcl(2) expression. An
      increase in Bax/Bcl(2) ratio suggests involvement of a mitochondrial mediated
      apoptotic processes. Our studies revealed a non significant (P > 0.05) increase
      in Bax/Bcl(2) ratio with Nos at a dose of 300 mg/kg/day, while a significant (P <
      0.001) increase in Bax/Bcl(2) ratio was observed with Nos doses of 450 and 550
      mg/kg/day. Further, Nos caused elevated apoptosis in tumor xenografts as
      evidenced by enhanced expression of caspase-3 and positive TUNEL staining in
      regressed tumor tissues, thus suggesting induction of apoptosis by mitochondrial
      pathway. CONCLUSION: Our studies suggest that potent antitumor activity of Nos
      against NSCLC cells. Oral administration of Nos showed significant reduction in
      tumor volume in human non-small cell lung tumor xenograft in nude mice in a dose
      dependant manner. Thus, Nos is a promising novel chemotherapeutic agent for the
      treatment of human lung cancer.

PMID- 18338173
TI  - Immunopathology of the eye. Introduction.

PMID- 18338174
TI  - Neonatal anterior cervical arachnoid cyst: case report and review of the
      literature.
AB  - OBJECTIVE: Anterior cervical arachnoid cysts are rare in the pediatric
      population, with only 16 cases reported. We present the first case of an anterior
      cervical arachnoid cyst in a neonate and review the literature on pediatric
      cervical arachnoid cysts. CLINICAL PRESENTATION: A 16-day-old baby girl with a
      history of myelomeningocele repair progressively developed symptoms of upper
      extremity weakness over the course of 2 weeks. Magnetic resonance imaging (MRI)
      demonstrated a compressive arachnoid cyst extending from C2 to C7. INTERVENTION:
      The child was taken for posterior cervical laminoplasty and cyst fenestration.
      Intraoperatively, diffuse cervical arachnoiditis was noted. Rapid improvement in
      upper extremity paresis was noted within 24 h of surgery, and MRI confirmed
      decompression of the cyst. However, flaccid upper extremity paresis recurred
      within 2 weeks. MRI confirmed recurrence of the anterior cervical arachnoid cyst.
      The child was taken for a secondary fenestration and stenting of the cyst. Only
      partial improvement in arm function was noted by 1 month following reoperation.
      CONCLUSION: Arachnoid cysts can be effectively treated with surgical
      fenestration, shunting, and complete or partial excision. Rapid identification
      and treatment results in improvement in myelopathic symptoms; however, the most
      efficacious treatment modality remains unknown. Of the 17 cases of anterior
      cervical arachnoid cysts reported in the literature, 11 (65%) have had either
      prior myelomeningocele repair or a history of spinal trauma. Anterior cervical
      arachnoid cysts should be considered in the differential diagnosis of acute onset
      myelopathy in the pediatric population especially in cases with a history of
      spinal trauma or myelomeningocele repair.

PMID- 18338175
TI  - Through the endoscope balloon dilation of ileocolonic strictures: prognostic
      factors, complications, and effectiveness.
AB  - BACKGROUND/AIMS: About half of all Crohn's disease (CD) patients undergo surgery
      at some point, many because of strictures. An alternative possibility is to
      dilate strictures endoscopically. However, little is known about prognostic
      factors. PATIENTS AND METHODS: Thirty-two patients with primary CD (n=2),
      radiogenic strictures (n=1), or postoperative strictures (27 because of CD; 2
      after resection because of cancer), were planned to undergo colonoscopic
      dilatation of which 25 patients were dilated (10 men; 15 women; median age 48).
      Length of stenosis, diameter of stricture, balloon size, smoking status, ulcer in
      the stricture, passage postdilatation, hemoglobin level, complications,
      redilatation, and subsequent surgery were recorded. Only patients with at least 6
      months follow up were included. RESULTS: Five out of 32 patients had no stenosis,
      marked inflammation, or fistulas adjacent to the stricture. One patient each had
      a long stricture (8 cm) or a filiform stenosis ruling out dilatation [technical
      success, 25/27 (92.6%)]. Among these 25 patients, 39 colonoscopies with 51
      dilatations were performed. After a single dilatation, 52% were asymptomatic
      while 48% needed another intervention, half of them surgery. Bleeding without
      need for transfusion occurred in 3 out of 39 colonoscopies and one perforation
      required surgery. Significant prognostic factors were smoking and ulcers in the
      stricture (P<0.05 each). Some ulcers led to intussusception requiring surgery in
      spite of good dilatation results. CONCLUSION: Through the endoscope balloon
      stricture dilatation is a relatively safe and often effective treatment modality
      in ileocolonic strictures. The presence of ulcers in the stricture have a worse
      outcome as do smokers.

PMID- 18338176
TI  - A case of primary serous papillary carcinoma with unusual clinical presentation:
      distant lympho nodes metastasis without peritoneal dissemination.
AB  - CASE REPORT: A 50-year-old woman with primary serous papillary carcinoma (PSPC)
      of peritoneal origin located in the posterior uterine serosa and cul-de-sac
      without peritoneal dissemination. No peritoneal dissemination was detected but
      the tumor metastasized to para-aortic and supraclavicular lymph nodes. After
      first chemotherapy course, pericardial effusion occurred. A pericardiectomy was
      performed to prevent cardiac failure. Subsequent chemotherapy with paclitaxel and
      carboplatin was effective against this tumor CONCLUSION: In general, a typical
      type of PSPC usually develops distant metastasis with diffuse peritoneal
      dissemination; the present case shows unusual clinical behavior.

PMID- 18338177
TI  - Hysterectomy and women satisfaction: total versus subtotal technique.
AB  - INTRODUCTION: The impact of different surgical procedures on women's satisfaction
      after hysterectomy is a topical issue. The aim of this study was to investigate
      the impact of sub-total and total hysterectomy on women's satisfaction, evaluated
      with questionnaire assessment of sexual activity, body image, and health status.
      MATERIALS AND METHODS: A prospective, randomized, non-blind study was conducted.
      In the study period of 3 years, 105 women were enrolled and completed the
      questionnaires [EuroQol (EQ-5D), body image scale (BIS), sexual activity
      questionnaire] 2 weeks before and 1 year after surgery. RESULTS: Both total and
      sub-total hysterectomy resulted with improvements in the women's sexual
      satisfaction (1 year after surgery), but no statistically significant differences
      were reached between the two groups. A highly significant difference (P < 0.001)
      in the perception of the body image between total and sub-total hysterectomy, at
      1 year after surgery, was underlined. The health-related quality of life resulted
      significantly better in the "sub-total hysterectomy" group 1 year after surgery
      (P < 0.05). CONCLUSION: Considering these results, why should a total
      hysterectomy be performed, if the women's satisfaction seems to be higher using
      the sub-total technique? In our opinion, the woman undergoing hysterectomy for
      benign conditions must be counseled regarding the differences between the two
      techniques and, when possible, a choice must be offered to the woman.

PMID- 18338178
TI  - Available instruments for measurement of psychosocial factors in the work
      environment.
AB  - OBJECTIVE: To provide an overview of the spectrum of available for measurement
      and evaluation of work-related psychosocial factors. METHODS: We systematically
      searched the literature/internet to identify and describe the main available
      questionnaires and observational instruments for assessment of work-related
      psychosocial factors (with/without other job stressors). RESULTS: A total of 33
      instruments were identified (26 questionnaires, 7 observational), many (11
      questionnaires, 5 observational) linked to national institutions/intiatives.
      Accessibility of relevant information (on the internet or elsewhere) regarding
      the instruments varied widely. CONCLUSIONS: This summary of the range of
      instruments currently available for evaluation of multiple work stressors at
      individual, group and/or organizational levels may provide a useful tool for
      operators and researchers.

PMID- 18338179
TI  - Long-term follow-up in 54 surgically treated patients with gastrointestinal
      stromal tumours.
AB  - BACKGROUND: Gastrointestinal stromal tumours (GISTs) are the most common
      mesenchymal tumours of the alimentary tract. Since these tumours are rather
      resistant to radiation and conventional chemotherapy, prognosis may be poor.
      Imatinib, a KIT tyrosine kinase inhibitor, has been shown to have dramatic
      antitumour effects on GISTs; however, surgical en bloc resection of the tumour
      with free resection margins remains still the first option for cure. MATERIALS
      AND METHODS: Here, we present a retrospective study with 54 consecutive GIST
      patients who were treated surgically at our University Hospital between 1993 and
      2005 and were followed up at 5 and 10 years. RESULTS: The disease-specific
      survival rate was 94% at 1 year, 91% at 3 years, 76% at 5 years, and 72% at 10
      years. In univariate analysis, tumour size, mitotic rate, morphology, and
      necrosis predicted survival in patients with negative margins. Age, sex, and
      symptoms did not influence outcome. CONCLUSION: GISTs have a high incidence of
      associated secondary malignancies which may have a significant influence on
      prognosis and outcome. Patients with R0 resections had a significantly better
      survival rate of 86% at 5 years and of 81% at 10 years than those with R1 and R2
      resections (21% and 0%).

PMID- 18338180
TI  - The role of cattle in the epidemiology of Echinococcus granulosus in an endemic
      area of southern Italy.
AB  - An epidemiological and molecular survey was conducted to investigate the role of
      cattle in the transmission chain of cystic echinococcosis (CE) in the Campania
      region of southern Italy. Out of a total of 434 cattle examined for CE, 45
      (10.4%) were found infected. A total of 363 cysts were collected from the
      infected animals: 239 in the liver and 124 in the lungs. The cysts were either
      sterile (42.7%) or calcified/caseous (57.3%); no fertile cysts were found. Most
      of the cysts had sizes <3 cm (77.1%) and were unilocular (78.8%). The results of
      the linear regression model did not show any significant correlation between the
      age of infected cattle and the number of cysts. The sequencing of the
      mitochondrial cytochrome C oxidase subunit 1 (CO1) gene of 40 hydatid cysts
      produced sequences of 419 bp for each sample analyzed. Alignment of the obtained
      sequences with those present in GenBank showed 100% identity with the common
      sheep G1 (n=21 cysts), the Tasmanian sheep G2 (n=2 cysts), and the buffalo G3
      (n=17 cysts) strains, which constitute the species Echinococcus granulosus sensu
      stricto. The findings reported in the present study show that CE is widespread in
      cattle bred in the Campania region of southern Italy. However, the absence of
      fertile cysts and of the cattle strain (G5, E. ortleppi) suggests that cattle
      would not have any role in the persistence of this important zoonosis but rather
      a role as indicators of CE infection in this endemic area.

PMID- 18338181
TI  - High intragenotypic diversity of Giardia duodenalis in dairy cattle on three
      farms.
AB  - Fifty-eight Giardia duodenalis-positive fecal specimens from three dairy farms in
      Georgia, USA were genotyped and subtyped by sequence analysis of the
      triosephosphate isomerase gene. Both the livestock-specific assemblage E and the
      potentially zoonotic assemblage A were found, with the former assemblage detected
      in 83% of the specimens. A high degree of genetic polymorphism was evident within
      assemblage E, with 11 distinct subtypes identified, eight of which represented
      new subtypes. Three subtypes were identified in assemblage A, with the subtype A2
      transiently found in calves and cows on one farm. All farms had multiple
      assemblage E subtypes circulating in cattle at each sampling, and concurrent
      infection with mixed subtypes or genotypes occurred in 24% of animals. Thus, the
      high intensity of G. duodenalis transmission is not only reflected by the high
      prevalence of the infection but also by the high intragenotypic diversity and
      concurrent occurrence of mixed infections. The zoonotic potential of bovine G.
      duodenalis needs to be further studied by extensive characterization of
      assemblage A specimens at the subtype level.

PMID- 18338182
TI  - Examination of the role of FMRFamide-related peptides in the circadian clock of
      the cockroach Leucophaea maderae.
AB  - The accessory medulla, the circadian clock of the cockroach Leucophaea maderae,
      is abundant in neuropeptides. Among these neuropeptides are the FMRFamide-related
      peptides (FaRPs), which generally share the C-terminal RFamide. As a first step
      toward understanding the functional role of FaRPs in the circadian clock of the
      cockroach, immunocytochemistry with antisera against various FaRPs, MALDI-TOF
      mass spectrometry, and injections of two FaRPs combined with running-wheel assays
      were performed. Prominent FMRFamide-like immunoreactivity was found in maximally
      four soma clusters associated with the accessory medulla and in most neuropils of
      the protocerebrum. By MALDI-TOF mass spectrometry, various extended FMRFamides of
      the cockroach L. maderae were partially identified in thoracic perisympathetic
      organs, structures known to accumulate extended FMRFamides in insects. By mass
      match, several of these peptides were also detected in the accessory medulla.
      Injections of FMRFamide and Pea-FMRFa-7 (DRSDNFIRF-NH(2)) into the vicinity of
      the accessory medulla caused time-dependent phase-shifts of locomotor activity
      rhythms at circadian times 8, 18, and 4. Thus, our data suggest a role for the
      different FaRPs in the control of circadian locomotor activity rhythms in L.
      maderae.

PMID- 18338183
TI  - Optimal fed-batch operation of recombinant cells subject to plasmid instability
      and death.
AB  - Optimal feed rate strategy is studied for fed-batch culture of recombinant cells
      with plasmid instability and with different death rates for the plasmid-free
      cells (PFC) and plasmid-bearing cells (PBC). Most of the fed-batch fermentation
      is known to have first-order singularity and therefore a single singular arc.
      However, this study shows that a singular arc with second-order singularity and
      therefore two distinct singular arcs are possible for a recombinant cell process
      if PFC and PBC are subjected to death, and their specific growth rates are
      proportional to each other. Two types of singular arcs are elucidated and
      analyzed. The optimal policies over the singular arcs are theoretically explored
      as these findings reveal qualitative information on the singular arc, which is
      critically important in providing the optimal initial conditions in numerical
      computation of optimal feed rate profile.

PMID- 18338184
TI  - Response of the grapevine rootstock richter 110 to inoculation with native and
      selected arbuscular mycorrhizal fungi and growth performance in a replant
      vineyard.
AB  - Two indigenous arbuscular mycorrhizal (AM) fungi from the Mediterranean wine
      growing area in the Northeast of Spain were isolated and classified as Glomus
      intraradices Schenck & Smith. Both native fungi were found to increase the growth
      of the vine rootstock 110 Richter under greenhouse conditions compared with G.
      intraradices (BEG 72) and a phosphorus (P) fertilization treatment. The
      effectivity of field inoculation of Cabernet Sauvignon plants grafted on Richter
      110 with the former native fungi and with G. intraradices BEG 72 in a replant
      vineyard severely infested by the root-rot fungus Armillaria mellea (Vahl ex Fr.)
      Kummer was assessed. The native fungi were not effective at enhancing plant
      development, and only G. intraradices BEG 72, resulted in a positive response.
      Field inoculation with this selected fungus increased plant shoot dry weight at
      the end of the first growing season.

PMID- 18338185
TI  - Endoscopic endonasal approach to the ethmoidal planum: anatomic study.
AB  - The endoscopic endonasal technique is currently used by otolaryngologists for the
      management of different extradural lesions located below the ethmoidal planum.
      The cooperation between ENTs and neurosurgeons has recently pushed the use of
      such approach also in the removal of some intradural lesions, which has promoted
      the interest for an anatomic study to identify the anatomical landmarks and the
      dangerous points during the endoscopic approach to this area. In six fresh
      cadaver heads, unilateral and bilateral measurements between the main landmarks
      of the approach were performed by means of an endoscopic endonasal approach. A
      wide exposure of the midline anterior skull base was realized. The maximum of
      lateral extension was obtained between the two medial orbital walls, at the
      middle of the cribriform plate (mean distance 25,33 mm), while the mean distance
      between the anterior and posterior ethmoidal arteries at the level of the lamina
      papyracea was 16 mm. The endoscopic endonasal route can be considered a minimally
      invasive technique to approach the ethmoidal planum. It requires adequate
      anatomical knowledge and endoscopic skill for its realization. Due to the wide
      window realizable through this corridor, it could be considered in selected cases
      for the removal of intradural lesions such as meningiomas or
      estesioneuroblastomas.

PMID- 18338186
TI  - Crystal structures of Lymnaea stagnalis AChBP in complex with neonicotinoid
      insecticides imidacloprid and clothianidin.
AB  - Neonicotinoid insecticides, which act on nicotinic acetylcholine receptors
      (nAChRs) in a variety of ways, have extremely low mammalian toxicity, yet the
      molecular basis of such actions is poorly understood. To elucidate the molecular
      basis for nAChR-neonicotinoid interactions, a surrogate protein, acetylcholine
      binding protein from Lymnaea stagnalis (Ls-AChBP) was crystallized in complex
      with neonicotinoid insecticides imidacloprid (IMI) or clothianidin (CTD). The
      crystal structures suggested that the guanidine moiety of IMI and CTD stacks with
      Tyr185, while the nitro group of IMI but not of CTD makes a hydrogen bond with
      Gln55. IMI showed higher binding affinity for Ls-AChBP than that of CTD,
      consistent with weaker CH-pi interactions in the Ls-AChBP-CTD complex than in the
      Ls-AChBP-IMI complex and the lack of the nitro group-Gln55 hydrogen bond in CTD.
      Yet, the NH at position 1 of CTD makes a hydrogen bond with the backbone carbonyl
      of Trp143, offering an explanation for the diverse actions of neonicotinoids on
      nAChRs.

PMID- 18338187
TI  - Biodiesel production from various feedstocks and their effects on the fuel
      properties.
AB  - Biodiesel, which is a new, renewable and biological origin alternative diesel
      fuel, has been receiving more attention all over the world due to the energy
      needs and environmental consciousness. Biodiesel is usually produced from food
      grade vegetable oils using transesterification process. Using food-grade
      vegetable oils is not economically feasible since they are more expensive than
      diesel fuel. Therefore, it is said that the main obstacle for commercialization
      of biodiesel is its high cost. Waste cooking oils, restaurant greases, soapstocks
      and animal fats are potential feedstocks for biodiesel production to lower the
      cost of biodiesel. However, to produce fuel-grade biodiesel, the characteristics
      of feedstock are very important during the initial research and production stage
      since the fuel properties mainly depend on the feedstock properties. This review
      paper presents both biodiesel productions from various feedstocks and their
      effects on the fuel properties.

PMID- 18338188
TI  - Sustainable bioethanol production combining biorefinery principles using combined
      raw materials from wheat undersown with clover-grass.
AB  - To obtain the best possible net energy balance of the bioethanol production the
      biomass raw materials used need to be produced with limited use of non-renewable
      fossil fuels. Intercropping strategies are known to maximize growth and
      productivity by including more than one species in the crop stand, very often
      with legumes as one of the components. In the present study clover-grass is
      undersown in a traditional wheat crop. Thereby, it is possible to increase input
      of symbiotic fixation of atmospheric nitrogen into the cropping systems and
      reduce the need for fertilizer applications. Furthermore, when using such wheat
      and clover-grass mixtures as raw material, addition of urea and other
      fermentation nutrients produced from fossil fuels can be reduced in the whole
      ethanol manufacturing chain. Using second generation ethanol technology mixtures
      of relative proportions of wheat straw and clover-grass (15:85, 50:50, and 85:15)
      were pretreated by wet oxidation. The results showed that supplementing wheat
      straw with clover-grass had a positive effect on the ethanol yield in
      simultaneous saccharification and fermentation experiments, and the effect was
      more pronounced in inhibitory substrates. The highest ethanol yield (80% of
      theoretical) was obtained in the experiment with high fraction (85%) of clover
      grass. In order to improve the sugar recovery of clover-grass, it should be
      separated into a green juice (containing free sugars, fructan, amino acids,
      vitamins and soluble minerals) for direct fermentation and a fibre pulp for
      pretreatment together with wheat straw. Based on the obtained results a
      decentralized biorefinery concept for production of biofuel is suggested
      emphasizing sustainability, localness, and recycling principles.

PMID- 18338189
TI  - Bioconversion of lignocellulosic biomass: biochemical and molecular perspectives.
AB  - In view of rising prices of crude oil due to increasing fuel demands, the need
      for alternative sources of bioenergy is expected to increase sharply in the
      coming years. Among potential alternative bioenergy resources, lignocellulosics
      have been identified as the prime source of biofuels and other value-added
      products. Lignocelluloses as agricultural, industrial and forest residuals
      account for the majority of the total biomass present in the world. To initiate
      the production of industrially important products from cellulosic biomass,
      bioconversion of the cellulosic components into fermentable sugars is necessary.
      A variety of microorganisms including bacteria and fungi may have the ability to
      degrade the cellulosic biomass to glucose monomers. Bacterial cellulases exist as
      discrete multi-enzyme complexes, called cellulosomes that consist of multiple
      subunits. Cellulolytic enzyme systems from the filamentous fungi, especially
      Trichoderma reesei, contain two exoglucanases or cellobiohydrolases (CBH1 and
      CBH2), at least four endoglucanases (EG1, EG2, EG3, EG5), and one beta
      glucosidase. These enzymes act synergistically to catalyse the hydrolysis of
      cellulose. Different physical parameters such as pH, temperature, adsorption,
      chemical factors like nitrogen, phosphorus, presence of phenolic compounds and
      other inhibitors can critically influence the bioconversion of lignocellulose.
      The production of cellulases by microbial cells is governed by genetic and
      biochemical controls including induction, catabolite repression, or end product
      inhibition. Several efforts have been made to increase the production of
      cellulases through strain improvement by mutagenesis. Various physical and
      chemical methods have been used to develop bacterial and fungal strains producing
      higher amounts of cellulase, all with limited success. Cellulosic bioconversion
      is a complex process and requires the synergistic action of the three enzymatic
      components consisting of endoglucanases, exoglucanases and beta-glucosidases. The
      co-cultivation of microbes in fermentation can increase the quantity of the
      desirable components of the cellulase complex. An understanding of the molecular
      mechanism leading to biodegradation of lignocelluloses and the development of the
      bioprocessing potential of cellulolytic microorganisms might effectively be
      accomplished with recombinant DNA technology. For instance, cloning and
      sequencing of the various cellulolytic genes could economize the cellulase
      production process. Apart from that, metabolic engineering and genomics
      approaches have great potential for enhancing our understanding of the molecular
      mechanism of bioconversion of lignocelluloses to value added economically
      significant products in the future.

PMID- 18338190
TI  - Scaffold-aided repair of articular cartilage studied by MRI.
AB  - OBJECTIVE: The objective of the study was to evaluate the ability of the
      noninvasive magnetic resonance techniques to monitor the scaffold-aided process
      of articular cartilage repair. MATERIALS AND METHODS: Defects of 4 mm in diameter
      and 3 mm in depth were created in right knees of 30 adolescent white New Zealand
      rabbits. Fourteen rabbits were implanted with poly(lactide-co-glycolic acid)
      (PLGA) scaffold trimmed to match the size and the shape of the defect (PLGA+
      group). No procedure was applied to the remaining 16 animals (PLGA- group).
      Animals were sacrificed sequentially at 4, 12, and 24 weeks after the surgery and
      magnetic resonance T (2)-weighted images (400 MHz) of the dissected bone plugs at
      eight different echo times were taken to derive T (2) relaxation time. The images
      and the T (2) time dependencies versus the tissue depth were statistically
      analyzed. Histological results of bone plugs were evaluated using
      semiquantitative histological scales. RESULTS: The results obtained for PLGA
      repair tissue were evaluated versus the PLGA- group and the healthy tissue
      harvested from the opposite knee (reference group), and compared with
      histological results (hematoxylin and eosin staining). The magnetic resonance
      images and T (2) relaxation time profiles taken 4 weeks after surgery for both
      the PLGA- and PLGA+ group did not reveal the tissue reconstruction. After 12
      weeks of treatment T (2) time dependence indicates a slight reconstruction for
      PLGA+ group. The T (2) time dependence obtained for PLGA+ samples taken after 24
      weeks of treatment resembled the one observed for the healthy cartilage,
      indicating tissue reconstruction in the form of fibrous cartilage. The tissue
      reconstruction was not observed for PLGA- samples. CONCLUSION: The study revealed
      correlation between magnetic resonance and histology data, indicating the
      potential value of using MRI and spatial variation of T (2) as the noninvasive
      tools to evaluate the process of articular cartilage repair. It also suggested,
      that the PLGA scaffold-aided treatment could help to restore the proper
      architecture of collagen fibrils.

PMID- 18338191
TI  - Magnetic field dependence of the distribution of NMR relaxation times in the
      living human brain.
AB  - OBJECTIVE: This study investigates the field dependence of the distribution of in
      vivo, whole-brain T1 values, and its usefulness for white matter/grey matter
      segmentation. Results on T1 values are presented on 12 healthy volunteers. T2 and
      T2* distributions and their field dependence have been measured on the same
      cohort of volunteers. In this paper, however, only the T2 and T2* results on a
      single volunteer are presented. The reported field dependence of T2 and T2*
      values should, therefore, be given less weight than that of T1 times. MATERIALS
      AND METHODS: Relaxation times were measured in vivo on 12 healthy volunteers,
      using three nearly identical whole-body scanners, operating at field strengths of
      1.5, 3, and 4 T and employing nearly identical software platforms and very
      similar hardware. T1 mapping was performed using TAPIR, a sequence based on the
      Look-Locker method. T2* mapping was performed with a multi-slice, multi-echo,
      gradient echo sequence. A multi-slice, multi-echo T2 mapping sequence based on
      the Carr-Purcell-Meiboom-Gill (CPMG) method was used to map T2. For each
      volunteer, the global distribution of T1 relaxation times was described as the
      superposition of three Gaussian distributions. The field and age-dependence of
      the centroids and widths of the three Gaussians was investigated. The
      segmentation of the brain in white and grey matter was performed separately for
      each field strength. Using the T1 segmentation and the fact that all maps were
      coregistered, we investigated the distribution of T2 and T*(2) values separately
      for the white and grey matter and described them with a Gaussian distribution in
      each case. RESULTS: Multi-slice quantitative maps were produced for the
      relaxation parameters T1 (near whole-brain coverage with 41 slices), T2* (whole
      brain coverage, 55 slices), and T2 (27 slices). A clear age dependence was
      identified for grey matter T1 values and correlated with similar behaviour
      observed in a separate study of the brain water content. The increase with field
      strength of the bulk white and grey matter T1 values was well reproduced by both
      Bottomley's [1] and Fischer's [2] formulae, with parameters taken from the
      literature. The separation between the centroids was, however, either
      overestimated or underestimated by the two formulae. The width of the T1
      distributions was found to increase with increasing field. CONCLUSIONS: The study
      of the field dependence of the NMR relaxation times is expected to allow for
      better differentiation between regions which are structurally different, provide
      a better insight into the microscopic structure of the brain and the molecular
      substrate of its function.

PMID- 18338192
TI  - Enhanced corticomotor excitability with dynamic fatiguing exercise of the lower
      limb in multiple sclerosis.
AB  - OBJECTIVE: To determine if task performance and fatigability during rapid
      repetitive exercise of the lower limb differ in a group of MS subjects compared
      to a control group, and what central changes accompany the development of fatigue
      and the period of recovery. METHODS: Transcranial magnetic stimulation (TMS) was
      used to compare motor evoked potential (MEP) responses between 10 clinically
      definite MS subjects (7F, 33-64 years of age; EDSS <or= 4; MRC grade >or= 4/5)
      and 13 control subjects during and after 5 bouts of a 15-second maximum rate foot
      tapping task performed at 1 minute intervals. RESULTS: Maximum voluntary
      contraction (MVC) force of ankle dorsiflexion was lower (15 %) in the MS group
      compared to controls; however there were no differences in the rate of foot
      tapping. The rate of foot tapping decreased during each bout of exercise to a
      comparable degree in both groups, but there was no overall deterioration in
      performance across the 5 repeat bouts in either group. MS subjects showed a
      greater decline in strength than controls after exercise (20.7+/-7.7% vs. 6+/
      3.6%; p<0.05). MEP amplitude increased significantly for the exercised limb in
      both groups, but the increase was greater in MS subjects (65.9+/-27% vs. 31+/
      19.6%; MS vs. control; p<0.05). MEP amplitude also increased for the non
      exercised limb in controls (40.6+/-15.6%, p<0.01) but not in MS subjects.
      CONCLUSIONS: Mild to moderately affected MS subjects can perform a fatiguing
      exercise requiring a high level of central motor control but this is associated
      with a greater strength loss and increase in corticomotor excitability compared
      to unaffected individuals. SIGNIFICANCE: Central adaptive processes are likely to
      have a significant role in maintaining task performance in MS.

PMID- 18338193
TI  - Deep brain stimulation for dystonia: outcome at long-term follow-up.
AB  - OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic
      option for patients with insufficient benefit from conservative treatment.
      METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4),
      generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige
      syndrome (1) were available for formal follow-up at three years postoperatively,
      and beyond up to 10 years. All patients had undergone pallidal stimulation except
      one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS:
      Maintained improvement was seen in all patients with pallidal stimulation up to
      10 years after surgery except in one patient who had a relative loss of benefit
      in dystonia ratings but continued to have improved disability scores. After nine
      years of chronic thalamic stimulation there was a mild loss of efficacy which was
      regained when the target was changed to the pallidum in the patient with
      paroxysmal dystonia. There were no major complications related to surgery or to
      chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in
      general. CONCLUSION: DBS maintains marked long-term symptomatic and functional
      improvement in the majority of patients with dystonia.

PMID- 18338194
TI  - Lipid profile, statin use, and outcome after intravenous thrombolysis for acute
      ischaemic stroke.
AB  - BACKGROUND: Low cholesterol levels have been associated with an increased risk of
      haemorrhagic stroke. This study investigated whether lipid levels or prior statin
      use influence outcome in patients with acute ischaemic stroke treated with IV
      thrombolysis. METHODS: The relation between admission lipid levels or statin use
      and both the development of symptomatic intracerebral haemorrhage (sICH) and 3
      months functional outcome was assessed in a prospective hospital-based stroke
      registry comprising 252 patients treated with IV tissue plasminogen activator
      (tPA). The fasting status of the patients was unknown. Favourable outcome at 3
      months was defined as a modified Rankin scale score <or= 2. Logistic regression
      analysis was performed with adjustment for possible confounders. RESULTS: Low
      density lipoprotein (LDL), total cholesterol levels, and statin use were not
      associated with sICH. Mean triglyceride levels were significantly higher (2.5
      mmol/L vs 1.8 mmol/L, p = 0.02) and high density lipoprotein (HDL) was
      significantly lower (1.0 mmol/L vs 1.2 mmol/L, p = 0.03) in patients with sICH
      than in patients without sICH. Multivariable analysis showed that higher
      triglyceride levels were independently associated with sICH (OR 2.16 per mmol/ L
      increase, 95 % CI 1.20-3.91, p = 0.01). There was no relation between any of the
      lipid levels or statin use and functional outcome at 3 months. CONCLUSIONS: High
      admission triglyceride levels were independently associated with a higher risk of
      sICH, but were not associated with a reduced chance of a favourable functional
      outcome at 3 months. Total cholesterol levels, LDL levels and statin use had no
      influence on both the occurrence of sICH or functional outcome.

PMID- 18338195
TI  - What should be defined as good outcome in stroke trials; a modified Rankin score
      of 0-1 or 0-2?
AB  - BACKGROUND AND PURPOSE: Good outcome in stroke trials has been defined as a
      modified Rankin scale (mRs) score of 0-1 or 0-2. The aim of this study was to
      investigate the clinical meaning of these two dichotomies. METHODS: We studied
      152 patients six months post stroke using the mRs and a new disability measure
      the AMC Linear Disability Scale (ALDS) item bank. Descriptive statistics were
      used to show the ALDS scores by the levels of the mRs. To investigate the
      clinical meaning of the different definitions of good outcome, the mean
      probability to perform activities of daily life (ADL) of all mRs grades and these
      two dichotomies was calculated. RESULTS: The ability to perform difficult ALDS
      items declined gradually with increasing mRs grade. When favourable outcome is
      defined as mRs 0-1, 15 % of the cohort has a good outcome; of these patients 84 %
      were likely to perform outdoor activities. If good outcome is defined as mRs 0-2,
      the percentage of patients with good outcome increased to 37 %, whereas 66 % of
      these patients were likely to perform outdoor activities. CONCLUSION: If good
      outcome is defined as the ability to perform outdoor activities mRs 0-1 should be
      chosen. If complex ADL are considered as good outcome mRs 0-2 is the outcome
      measure of choice. Independent of which outcome measure is chosen, the treatment
      effect in clinical trials must be large before good outcome is achieved.
      Therefore, it is likely that clinically important treatment effects can be missed
      in clinical trials with both these mRs endpoints.

PMID- 18338196
TI  - Axonal function in a family with episodic ataxia type 2 due to a novel mutation.
AB  - Episodic ataxia type 2(EA-2) is a rare, autosomal dominant disorder characterised
      by recurrent episodes of ataxia and dysarthria,due to mutations in the CACNA1A
      gene on chromosome 19 encoding voltage-dependent Ca2+ channels. The aim of the
      present study was to explore whether axonal membrane properties, assessed using
      nerve excitability techniques, were abnormal in patients with EA-2 . Nerve
      excitability techniques were applied to the median nerve of three individuals
      from three generations of a single family, all of whom had typical features of EA
      2. This family was found to have a novel mutation at codon 1451 of the Ca2+
      channel alpha 1A subunit. Nerve excitability testing demonstrated significant
      abnormalities,with all patients outside the normal 95 % confidence limits in
      having a high rheobase and reduced early hyperpolarizing threshold electrotonus.
      On average there were also significant reductions in refractoriness,late sub
      excitability and early depolarizing threshold electrotonus. Mathematical
      modelling indicated that a similar pattern of abnormalities may result from a
      reduced voltage dependence of slow K+ channels (KCNQ channels). There are
      significant and distinctive changes in peripheral nerve excitability in EA-2
      patients,which are presumably induced indirectly. These findings raise the
      possibility that excitability testing may prove a convenient screening test for
      patients with this suspected channelopathy.

PMID- 18338197
TI  - Movement disorders at a university hospital emergency room. An analysis of
      clinical pattern and etiology.
AB  - We prospectively evaluated the clinical features and etiologies of all common
      categories of movement disorder seen in the emergency room (ER) of an urban
      university hospital over a period of 12 months. We divided movement disorders
      according to the presenting phenomenology likely to dominate the clinical
      presentation, that is, gait disorder, tremor, dystonia, myoclonus, and acute
      akinetic crisis and classified a specific etiology in the individual
      phenomenology. In one year, there were 60,002 ER visits; of these, 58 (0.09 %)
      were diagnosed as a primary movement disorder. The most common clinical
      presentation was gait disorder (n = 21, 36.2 %), followed by myoclonus (n = 16,
      27.6 %), dystonia (n = 10, 17.2 %), tremor (n = 8, 13.8 %), and acute akinetic
      crisis (n = 3, 5.2 %). Comparing the movement disorders, the mean age of the
      patients with dystonia was significantly lower than that of patients with other
      movement disorders (P < 0.001). Of the patients, 37 (63.8 %) had drug-related
      movement disorders. The contribution of drugs was significantly higher in
      patients with dystonia compared with the other movement disorders (P < 0.01). Our
      study showed that a large proportion of the movement disorders seen in the ER are
      drug-related. Careful selection of drugs while prescribing would decrease
      movement disorder-related visits to the ER.

PMID- 18338198
TI  - Psychiatric comorbidity in different organic vertigo syndromes.
AB  - OBJECTIVE: A high degree of psychiatric disorders has repeatedly been described
      among patients with organic vertigo syndromes and attributed to vestibular
      dysfunction. Yet almost no investigations exist which differentiate between
      various organic vertigo syndromes with regard to psychiatric comorbidity. The
      following prospective, interdisciplinary study was carried out to explore whether
      patients with different organic vertigo syndromes exhibit different psychological
      comorbidities. METHODS: 68 patients with organic vertigo syndromes (benign
      paroxysmal positioning vertigo (BPPV) n = 20, vestibular neuritis (VN) n = 18,
      Meniere's disease (MD) n = 7, vestibular migraine (VM) n = 23) were compared with
      30 healthy volunteers. All patients and control persons underwent structured
      neurological and neuro-otological testing. A structured diagnostic interview (-I)
      (SCID-I) and a battery of psychometric tests were used to evaluate comorbid
      psychiatric disorders. RESULTS: Patients with VM and MD showed significantly
      higher prevalence of psychiatric comorbidity (MD = 57%, VM = 65%) especially with
      anxiety and depressive disorders, than patients with VN (22%) and BPPV (15 %)
      compared to normal subjects (20 %). These elevated rates of comorbidities
      resulted in significantly elevated odds-ratios (OR) for the development of
      comorbid psychiatric disorders in general (for VM OR = 7.5, for MD OR = 5.3) and
      especially for anxiety disorders (for VM OR = 26.6, for MD OR = 38.7).
      CONCLUSION: As a consequence, a structured psychological and psychometric testing
      and an interdisciplinary therapy should be proceeded in cases with complex and
      prolonged vertigo courses, especially in patients with VM and MD. Possible
      reasons of these unexpected results in VM and MD are discussed.

PMID- 18338199
TI  - Cognitive function correlates with frontal white matter apparent diffusion
      coefficients in patients with leukoaraiosis.
AB  - BACKGROUND AND AIMS: Diffusion weighted imaging (DWI) displays a high sensitivity
      to white matter changes, even in areas where no lesions are visible. Correlation
      with vascular risk factors and cognitive dysfunction seems to be feasible using
      this technique. We aimed to test relations between age, blood pressure and
      cognitive function,with lesion load and average Apparent Diffusion Coefficient
      (ADC) values in lesioned (LWM) and in normal appearing white matter (NAWM), in
      patients with age related white matter lesions (ARWML). METHODS: Subjects were 29
      patients (mean age 72.6 +/- 5.2 years) with different severity of ARWML on MRI
      and no (or mild) disability assessed by the Instrumental Activities of Daily
      Living Scale. Imaging lesion load was quantified in bilateral frontal, temporal,
      parieto-occipital, basal ganglia and infratentorial regions, using a simple
      visual rating scale; ADC was measured bilaterally in Regions of Interest in
      parieto-occipital and frontal NAWM, and in frontal periventricular LWM.
      Neuropsychological examination consisted of Raven Colored Progressive Matrices,
      Rey's Complex Figure, Digit Canceling. Symbol digit Substitution, Inverse Digit
      Repetition and Verbal Fluency tests. RESULTS: Visual scales scores and ADC were
      significantly higher in frontal and parieto-occipital regions. Both were
      significantly correlated to age and blood pressure, in frontal (visual scale
      scores and ADC) and parieto-occipital regions (ADC). Attention skills were
      negatively correlated to ADC in LWM and NAWM in frontal regions and with frontal
      region visual scale scores. CONCLUSION: Our findings suggest that severity of
      white matter ischemic changes is correlated with worse cognitive function, as
      well as advanced age and higher blood pressure.A higher vulnerability of frontal
      white matter to vascular disease seems to play an important role in executive
      dysfunction, mainly determined by impairment of attentional skills.DWI results
      suggest this could be true even for NAWM.

PMID- 18338200
TI  - Polymorphisms in the proteasomal subunit alpha4 are not associated with
      Parkinson's disease.

PMID- 18338201
TI  - Aberrations of dermal connective tissue in patients with cervical artery
      dissection (sCAD).
AB  - Spontaneous cervical artery dissection (sCAD) is a common cause of stroke in
      patients below 55 years of age. Hereditary connective tissue disorders, including
      Ehlers-Danlos syndrome type IV, have been associated with sCAD and
      suprastructural abnormalities of both collagen fibrils and elastic fibers have
      been found by transmission electron microscopy in the dermis of about 50% of sCAD
      patients. Here, we investigated dermal connective tissue abnormalities using a
      novel method. Transmission and immunogold electron microscopy were used to study
      mechanically generated fragments of dermal matrix suprastructures, in particular
      collagen fibrils. Analysis of dermal tissue of sCAD patients revealed
      structurally abnormal collagen fibrils with irregularly contoured surfaces and
      increased diameters, often associated with a faint or absent banding pattern.
      Interestingly, only a small number of fibrils displayed short abnormal sections
      along the length of the fibril. Collagens I and III were present in normal as
      well as abnormal sections of the fibrils.However, immunogold labeling for the two
      proteins was strongly increased in abnormal sections.A systematic blinded
      investigation of skin biopsies of 31 sCAD patients and 17 controls revealed
      abnormal collagen fibrils in 7 sCAD patients but none of the controls. We
      conclude that approximately 20% of sCAD patients show collagen fibril
      alterations, establishing a promising basis for further investigation of
      connective tissue aberrations in skin biopsies of sCAD patients.

PMID- 18338202
TI  - AMP deaminase deficiency in skeletal muscle is unlikely to be of clinical
      relevance.
AB  - BACKGROUND: The homozygous c.34C>T mutation in the AMPD1 gene encoding the muscle
      specific isoform of AMP deaminase (AMPD) accounts for the vast majority of
      inherited skeletal muscle AMPD deficiencies. It is controversial (i) whether AMPD
      deficiency is associated with exercise-induced complaints and (ii) whether an
      acquired form exists in which an underlying neuromuscular disorder additionally
      lowers the AMPD activity. DESIGN: c.34C>T mutation (homozygous- TT, heterozygous
      CT,wildtype-CC) was screened in 107 healthy blood donors and 294 patients with
      skeletal muscle biopsy including 200 with exercise-induced complaints. Additional
      screening for c.468G > T and c.860A > T mutations was performed in all CT.AMPD
      was analysed histochemically and biochemically. RESULTS: The mutant allele
      frequency (MAF) was not different in blood donors, patients with muscle biopsy,
      and the subgroup with exercise-induced complaints (12.9-16.8 %). CT was found in
      63 and TT in 13 patients. The c.468G>T mutation was not detected. The c.860A > T
      mutation was found in 2.8 % blood donors and 1.6% CT. AMPD activities showed a
      substantial overlap in CC and CT, but not with TT. AMPD activities in TT, CT, and
      CC did not differ in patients with a defined neuromuscular disorder and those
      with only exercise-induced complaints. In TT, CT, and CC there were no
      differences in the frequency of signs and symptoms, hyperCKemia, or
      myopathological biopsy pattern. CONCLUSION: MAF did not differ in normal and
      diseased populations. The frequency of exertion-induced complaints was not higher
      in TT than CC. There was no specific phenotype of TT and no evidence for an
      acquired form of AMPD deficiency.

PMID- 18338203
TI  - Reduction of urinary levels of pyridinoline and deoxypyridinoline and serum
      levels of soluble receptor activator of NF-kappaB ligand by etanercept in
      patients with rheumatoid arthritis.
AB  - The effects of soluble TNF-alpha receptor, etanercept, on bone metabolism were
      investigated in patients with rheumatoid arthritis (RA). Thirty RA patients were
      administered etanercept once or twice a week for more than 6 months. We evaluated
      clinical and laboratory parameters and measured urinary excretion levels of
      pyridinoline (PYD), deoxypyridinoline (DPD), cross-linked N-telopeptides of type
      I collagen (NTX), and serum levels of bone alkaline phosphatase (BAP),
      osteoprotegerin (OPG), and soluble receptor activator of NFkappaB ligand (sRANKL)
      at the baseline and at 3 and 6 months after initial treatment with etanercept.
      Etanercept treatment resulted in an improvement of symptoms due to RA and in a
      reduction of urinary excretion levels of PYD and DPD as well as serum sRANKL
      levels, with a significant difference at 6 months, and an increase of serum BAP
      levels at 3 and 6 months after the initial treatment with etanercept. Urinary NTX
      and serum OPG levels did not show a significant change at 3 and 6 months after
      the initial treatment, but serum OPG levels did show a reverse correlation with
      serum CRP levels, suggesting that the regulation of inflammation in RA may result
      in an induction of OPG production. Etanercept may have the ability to reduce the
      levels of bone resorption markers and to increase the levels of a bone formation
      marker while reducing sRANKL formation in RA patients.

PMID- 18338204
TI  - Should the tube cholangiostomy be performed as a supplement procedure to
      duodenostomy for treatment or prevention of duodenal fistula?

PMID- 18338205
TI  - Continuous follow-up of surgical site infections for 30 days after colorectal
      surgery.
AB  - BACKGROUND: Surgical site infection (SSI) prolongs hospital stay, increases
      medical costs, and occasionally leads to mortality. Our goal was to clarify the
      differences in SSI incidence between our own data and the National Nosocomial
      Infections Surveillance (NNIS) data. METHODS: From January 2003 to December 2006,
      we prospectively collected surveillance data from patients who were undergoing
      elective colorectal resection at the Mie University Graduate School of Medicine.
      RESULTS: Three hundred fifty-five elective colorectal resections (144 colon
      surgeries, 211 rectal surgeries) were included. The median patient age was 57.4
      years. SSIs were identified in 60 patients. Cumulative SSI incidence was 16.9%.
      The average SSI onset was 8.7 days (range = 3-20 days) after operation. Nineteen
      patients (19/30:31.7%) developed SSI within 6 days of the operation. The
      incidence of SSI occurring within 6 days after the operation was 5.4%.
      CONCLUSION: Seventeen percent of SSIs occurred despite the use of perioperative
      management according to the CDC guidelines. We reported a much higher SSI
      incidence than that in the NNIS data. However, the SSI incidence within 6 days of
      surgery was similar to that of the NNIS data. The difference in SSI incidence
      between our data and that of the NNIS range may result from the different strict
      surveillance periods.

PMID- 18338206
TI  - Long-term follow-up of local rectal cancer surgery by transanal endoscopic
      microsurgery.
AB  - BACKGROUND: In 1997 we launched a prospective program of transanal endoscopic
      microsurgery (TEM) for the treatment of rectal cancer. METHODS: Suitability for
      TEM was based on endorectal ultrasound results, classified as follows: (I) benign
      tumors; (II) adenocarcinomas uT0 and uT1 with uN0; (III) adenocarcinomas uT2-
      uN0, low histological grade with intention to cure; and (IV) advanced stage
      adenocarcinomas with palliative care RESULTS: Transanal endoscopic microsurgery
      was performed in 218 patients: 122 adenomas, and 96 adenocarcinomas: group II-72,
      group III-19, and group IV-5. Follow-up was >24 months (median 59 months) in 61
      patients. Nine were lost to follow-up, and so 52 patients were studied: group II
      38, group III-11, and group IV-3. The Kaplan-Meier probability of nonrecurrence
      of adenocarcinoma by group was 93% in tumors in situ (Tis) and T1; and 77.8% in
      T2. The Kaplan-Meier probability of survival by group was 100% in Tis and T1 and
      82% in T2. CONCLUSIONS: Rates of recurrence and long-term survival in Tis and T1
      adenocarcinomas treated with TEM are similar to those in previously published
      reports using conventional surgery. Further studies are required in T2
      adenocarcinomas to determine a definitive strategy.

PMID- 18338207
TI  - Simultaneous use of laparoscopy and endoscopy for minimally invasive resection of
      gastric subepithelial masses - analysis of 93 interventions.
AB  - BACKGROUND: Subepithelial gastric tumors are common findings during upper
      gastrointestinal endoscopy. Tumor resection is mostly done laparoscopically, but
      there is still discussion concerning the size of lesion for which the treatment
      may be minimally invasive; additionally there is very little data available
      concerning patient outcome after minor access surgery. METHODS: Clinicopathologic
      features and survival data of 93 consecutive patients undergoing a combined
      laparoscopic-endoscopic approach for gastric submucosal tumors were prospectively
      analyzed. Analysis included preoperative diagnostic work-up, perioperative data,
      and postoperative complications. Follow-up was carried out for patients with GIST
      to check for tumor recurrence. RESULTS: It was possible to resect 88 of 93
      lesions by the laparoscopic-endoscopic approach, with tumor-free margins in all
      patients. Intraoperative endoscopy facilitated exact tumor localization in 92
      patients. Most lesions were removed by endoscopic-laparoscopic wedge resection
      or, less frequently, by a combined transgastric approach. Mean operative time was
      90.7 min; the postoperative hospitalization was 7.3 days. Adverse events appeared
      in 7.5%, and conversion to open surgery was required in 6.5%. For patients
      suffering from gastrointestinal stromal tumors, there was no tumor recurrence at
      a mean follow-up of 40 months. CONCLUSIONS: Combined laparoscopic-endoscopic
      "rendez-vous" procedures are easy to perform and offer a curative approach for
      almost all gastric submucosal lesions. The technique is associated with low
      morbidity and short hospitalization. Though even patients with large GISTs of
      intermediate and high risk were treated, no tumor recurrence has been observed to
      date.

PMID- 18338208
TI  - Expression of parafibromin in distant metastatic parathyroid tumors in patients
      with advanced secondary hyperparathyroidism due to chronic kidney disease.
AB  - BACKGROUND: Recently, somatic inactivating mutations in HRPT2 have been reported
      in the majority of sporadic parathyroid carcinoma in primary hyperparathyroidism
      (HPT). Parafibromin is a tumor suppressor protein encoded by HRPT2, and loss of
      nuclear expression of parafibromin was found in approximately 70% of the
      carcinoma. In secondary HPT due to chronic kidney disease (CKD), parathyroid
      carcinoma is very rare and whether HRPT2 plays a role in the carcinogenesis in
      these cases is not clear. We evaluated the expression of parafibromin in
      hemodialysis patients with distant metastatic parathyroid tumors. METHODS:
      Between June 1973 and December 2006, 2,142 patients underwent parathyroidectomy
      (PTx) for secondary HPT in our department. We encountered five (0.23%) patients
      with distant metastatic parathyroid tumors. We evaluated the immunohistochemistry
      for parafibromin in eight primary parathyroid glands removed from the neck at the
      initial operation and/or at reoperation and seven distant metastatic tumors
      resected at reoperation. RESULTS: In only one lung metastatic parathyroid tumor,
      negative staining for parafibromin was detected. In the other three lung, two
      regional node, and one chest wall metastatic parathyroid tumor, parafibromin was
      strongly stained in the nuclei of the parathyroid cells. Among eight primary
      glands, except for one with weakly positive staining, the expression of
      parafibromin was detected diffusely and strongly. CONCLUSION: We conclude that
      the inactivating mutations and/or allelic loss of the HRPT2 gene may not play a
      major role in parathyroid carcinogenesis in secondary HPT due to CKD, but in
      these cases cancer development may be associated with a heterogeneous genetic
      disorder.

PMID- 18338209
TI  - Prevention of anastomotic stricture with a purse-string suture technique on the
      gastric side during esophageal carcinoma operations: retrospective study of 463
      consecutive cases.
AB  - OBJECTIVE: The objective of this study was to investigate the effect of a gastric
      side purse-string technique on anastomotic strictures during esophageal carcinoma
      operations. METHODS: From 1996 to 2005, esophageal carcinoma operations were
      performed on 1128 consecutive patients. Among them, 463 underwent esophagogastric
      anastomosis with purse-string sutures on the gastric side (purse group) and the
      other 665 did not (nonpurse group). Anastomotic strictures, reflux, and leakage
      were analyzed and compared between the two groups after the operations. RESULTS:
      Complete follow-up was conducted on all 1128 patients within 6 months after the
      operation. In contrast to the nonpurse group with a postoperative anastomotic
      stricture rate of 5.4% (36/665), the purse group demonstrated a significantly
      lower rate (0.2%, 1/463). The occurrence rates of anastomotic leakage in the
      nonpurse and purse groups were 0.9% (6/665) and 0.4% (2/463), respectively. Of
      the 17 cases of gastroesophageal reflux, 15 (15/665, 1.8%) were found in the
      nonpurse group and 2 (2/463, 1.1%) in the purse group. CONCLUSIONS: Thus, a purse
      string suture technique on the gastric side might be an effective method for
      preventing the occurrence of anastomotic strictures after esophageal resection.

PMID- 18338210
TI  - Appraisal of hepatic resection in the treatment of hepatocellular carcinoma with
      severe thrombocytopenia.
AB  - BACKGROUND: Hepatic resection for hepatocellular carcinoma (HCC) patients with
      liver cirrhosis and severe hypersplenic thrombocytopenia is risky and
      controversial. METHODS: From 1989 to 2005, 341 patients underwent hepatic
      resection for HCC in our hospital. Of these, 15 patients were concomitant with
      severe thrombocytopenia (platelet count, <or=5 x 10(4)/mm(3)), and their clinical
      outcomes were retrospectively reviewed. RESULTS: Among the 15 patients, 11
      underwent hepatectomy alone and 4 underwent concomitant splenectomy. The mean
      preoperative platelet count was 4.2 +/- 0.8 x 10(4)/mm(3) (range, 1.9-5 x
      10(4)/mm(3)). The surgical procedures performed were partial resection in five
      patients, subsegmentectomy in three, and segmentectomy in seven. A blood
      transfusion was required for 11 of 15 patients, and 8 of these received a
      platelet-rich plasma transfusion. With the exception of one patient who suffered
      from postoperative liver failure, all the patients had an uneventful
      postoperative course. The 3-year cumulative survival rate of these patients was
      comparable to those without thrombocytopenia. CONCLUSIONS: Severe
      thrombocytopenia alone is not a contraindication for hepatectomy in patients with
      HCC associated with liver cirrhosis. For these patients, hepatic resection
      hepatectomy alone or concomitant splenectomy-should be considered as a treatment
      option.

PMID- 18338211
TI  - Percutaneous transhepatic venous angioplasty and stenting in a 9-month-old
      patient with hepatic vein obstruction after partial liver transplantation.
AB  - Hepatic venous outflow obstruction is a rare but serious complication after liver
      transplantation. We report ultrasound-guided percutaneous transhepatic stent
      placement in a 9-month-old infant with a left lateral split liver transplantation
      with near-complete hepatic vein obstruction.

PMID- 18338212
TI  - Buttock claudication and erectile dysfunction after internal iliac artery
      embolization in patients prior to endovascular aortic aneurysm repair.
AB  - Coil embolization of the internal iliac artery (IIA) is used to extend the
      application of endovascular aneurysm repair (EVAR) in cases of challenging iliac
      anatomy. Pelvic ischemia is a complication of the technique, but reports vary as
      to the rate and severity. This study reports our experience with IIA embolization
      and compares the results to those of other published series. The vascular unit
      database of the Leicester Royal Infirmary was used to identify patients who had
      undergone IIA coil embolization prior to EVAR. Data were collected from hospital
      case notes and by telephone interviews. Thirty-eight patients were identified; 29
      of these were contactable by telephone. A literature search was performed for
      other studies of IIA embolization and the results were pooled. In this series
      buttock claudication occurred in 55% (16 of 29 patients) overall: in 52% of
      unilateral embolizations (11 of 21) and 63% of bilateral embolizations (5 of 8).
      New erectile dysfunction occurred in 46% (6 of 13 patients) overall: in 38% of
      unilateral embolizations (3 of 8) and 60% of bilateral embolizations (3 of 5).
      The literature review identified 18 relevant studies. The results were pooled
      with our results, to give 634 patients in total. Buttock claudication occurred in
      28% overall (178 of 634 patients): in 31% of unilateral embolizations (99 of 322)
      and 35% of bilateral embolizations (34 of 98) (p = 0.46, Fisher's exact test).
      New erectile dysfunction occurred in 17% overall (27 of 159 patients): in 17% of
      unilateral embolizations (16 of 97) and 24% of bilateral embolizations (9 of 38)
      (p = 0.33). We conclude that buttock claudication and erectile dysfunction are
      frequent complications of IIA embolization and patients should be counseled
      accordingly.

PMID- 18338213
TI  - Adolescent external iliac artery trauma: recurrent aneurysmal dilatation of an
      iliofemoral saphenous vein graft treated by stent-grafting.
AB  - An adolescent male sustained a severe penetrating injury to the external iliac
      artery. Emergency surgical revascularization was with a reversed long saphenous
      vein interposition graft. The primary graft and the subsequent revision graft
      both became aneurysmal. The second graft aneurysm was successfully excluded by
      endovascular stent-grafts with medium-term primary patency. A venous graft was
      used initially rather than a synthetic graft to reduce the risk of infection and
      the potential problems from future growth. Aneurysmal dilatation of venous grafts
      in children and adolescents is a rare but recognized complication. To the best of
      our knowledge, exclusion of these aneurysms with stent-grafts has not been
      previously reported in the adolescent population.

PMID- 18338214
TI  - Effects of intrinsic and extrinsic noise can accelerate juxtacrine pattern
      formation.
AB  - Epithelial pattern formation is an important phenomenon that, for example, has
      roles in embryogenesis, development and wound-healing. The ligand Epithelial
      Growth Factor (EGF) and its receptor EGF-R, constitute a system that forms
      lateral induction patterns by juxtacrine signalling-binding of membrane-bound
      ligands to receptors on neighbouring cells. Owen et al. developed a generic
      ordinary differential equation model of juxtacrine lateral induction that
      exhibits stable patterning under some conditions. The model predicts relatively
      slow pattern formation. We examine here the effects of both intrinsic and
      extrinsic cellular noise arising from the stochastic treatment of this model, and
      show that this noise could have an accelerating effect on the patterning process.

PMID- 18338215
TI  - Racial segregation and disparities in cancer stage for seniors.
AB  - BACKGROUND: Disparities in cancer survival may be related to differences in
      stage. Segregation may be associated with disparities in stage, particularly for
      cancers for which screening promotes survival. OBJECTIVES: The objective of the
      study was to examine whether segregation modifies racial/ethnic disparities in
      stage. DESIGN: The design of the study was analysis of Surveillance,
      Epidemiology, and End Results Medicare data for seniors with breast, colorectal,
      lung, and prostate cancer (n = 410,870). MEASUREMENTS AND MAIN RESULTS: The
      outcome was early- versus late-stage diagnosis. Area of residence was categorized
      into 4 groups: low segregation/high income (potentially the most advantaged),
      high segregation/high income, low segregation/low income, and high
      segregation/low income (possibly the most disadvantaged). Blacks were less likely
      than whites to be diagnosed with early-stage breast, colorectal, or prostate
      cancer, regardless of area. For colorectal cancer, the black/white disparity was
      largest in low-segregation/low-income areas (black/white odds ratio [OR] of early
      stage 0.51) and smallest in the most segregated areas (ORs 0.71 and 0.74, P <
      .005). Differences in disparities in stage by area category were not apparent for
      breast, prostate, or lung cancer. Whereas there were few Hispanic-white
      differences in early-stage diagnosis, the Hispanic/white disparity in early-stage
      diagnosis of breast cancer was largest in low-segregation/low-income areas
      (Hispanic/white OR of early stage 0.54) and smallest in high-segregation/low
      income areas (OR 0.96, P < .05 compared to low-segregation/low-income areas).
      CONCLUSIONS: Disparities in stages for cancers with an established screening test
      were smaller in more segregated areas.

PMID- 18338216
TI  - Copal bone cement is more effective in preventing biofilm formation than Palacos
      R-G.
AB  - Bone cements loaded with combinations of antibiotics are assumed more effective
      in preventing infection than bone cements with gentamicin as a single drug.
      Moreover, loading with an additional antibiotic may increase interconnectivity
      between antibiotic particles to enhance release. We hypothesize addition of
      clindamycin to a gentamicin-loaded cement yields higher antibiotic release and
      causes larger inhibition zones against clinical isolates grown on agar and
      stronger biofilm inhibition. Antibiotic release after 672 hours from Copal bone
      cement was more extensive (65% of the clindamycin and 41% of the gentamicin
      incorporated) than from Palacos R-G (4% of the gentamicin incorporated). The
      higher antibiotic release from Copal resulted in a stronger and more prolonged
      inhibition of bacterial growth on agar. Bacterial colony counting and confocal
      laser scanning microscopy of biofilms grown on the bone cements suggest
      antibiotic release reduced bacterial viability, most notably close to the cement
      surface. The gentamicin-sensitive Staphylococcus aureus formed gentamicin
      resistant small colony variants on Palacos R-G and therefore Copal more
      effectively decreased biofilm formation than Palacos R-G.

PMID- 18338217
TI  - Curved-stem hip resurfacing: minimum 20-year followup.
AB  - Hip resurfacing is an attractive concept because it preserves rather than removes
      the femoral head and neck. Most early designs had high failure rates, but one
      unique design had a femoral stem. Because that particular device appeared to have
      better implant survival, this study assessed the clinical outcome and long-term
      survivorship of a hip resurfacing prosthesis. Four hundred forty-five patients
      (561 hips) were retrospectively reviewed after a minimum of 20 years' followup or
      until death; 23 additional patients were lost to followup. Patients received a
      metal femoral prosthesis with a small curved stem. Three types of acetabular
      reconstructions were used: (1) cemented polyurethane; (2) metal-on-metal; and (3)
      polyethylene secured with cement or used as the liner of a two-piece porous
      coated implant. Long-term results were favorable with the metal-on-metal
      combination only. The mean overall Harris hip score was 92 at 2 years of
      followup. None of the 121 patients (133 hips) who received metal-on-metal
      articulation experienced failure. The failure rate with polyurethane was 100%,
      and the failure rate with cemented polyethylene was 41%. Hip resurfacing with a
      curved-stem femoral component had a durable clinical outcome when a metal-on
      metal articulation was used.

PMID- 18338218
TI  - Metal ion accessibility of histidine-modified superfolder green fluorescent
      protein expressed in Escherichia coli.
AB  - Green fluorescent protein (GFP) is frequently utilized for metal ion detection
      and quantification. To improve the metal binding potential of GFP, three residues
      (N146, F165, and L201) were substituted to histidines. Each variant responded
      differently upon interaction with metal ions. More than 80% of N146H, having the
      most accessible surface area, could bind to immobilized metal ions. However, only
      F165H exhibited significant differences in quenching by soluble metal ions (22%
      fluorescence decrease) in comparison with the template protein (12%). These
      findings can be utilized for designing GFP variants for metal binding and sensor
      applications.

PMID- 18338219
TI  - Overexpression of a mitochondrial ATP synthase small subunit gene (AtMtATP6)
      confers tolerance to several abiotic stresses in Saccharomyces cerevisiae and
      Arabidopsis thaliana.
AB  - Mitochondrial F(1)F(0)-ATPase is a key enzyme in plant metabolism, providing
      cells with ATP that uses the transmembrane electrochemical proton gradient to
      drive synthesis of ATP. A 6 kDa protein (At3g46430) has been previously purified
      from Arabidopsis thaliana mitochondrial F(1)F(0)-ATPase. In this study, the gene
      (AtMtATP6; GenBank accession no. AK117680) encoding this protein was isolated
      from Arabidopsis and characterized. Northern blot analyses showed that the
      expression of AtMtATP6 gene in Arabidopsis suspension-cultured cells was induced
      by several abiotic stresses from salts, drought, and cold. Over-expression of
      AtMtATP6 gene in transgenic yeast and Arabidopsis plants increased the resistance
      to salts, drought, oxidative and cold stresses. Taken together, our data raise
      the possibility that induction of the F(1)F(0)-ATPase plays a role in stress
      tolerance.

PMID- 18338220
TI  - Correlation between cell morphology and aggrecan gene expression level during
      differentiation from mesenchymal stem cells to chondrocytes.
AB  - A morphological parameter of polygonal index was defined as the ratio of cell
      adhesion area versus the square of the major cell axis, and cells that had an
      adhesion area larger than 4000 mum(2) and a polygonal index larger than 0.3 were
      considered large polygonal cells. Cell morphology tended to change from
      fibroblast-like to polygonal and the percentage of the large polygonal cells
      increased almost in proportion to aggrecan mRNA expression level during the
      differentiation culture of mesenchymal stem cells (MSCs) to chondrocytes.
      Approximately 80% of the large polygonal cells were negative for MSC marker
      (CD90, CD166) expression and the aggrecan mRNA expression level of the large
      polygonal cells was markedly higher than that of cells with other morphologies.

PMID- 18338221
TI  - Metabolic alternations in SOD-deficient Escherichia coli cells when cultivated
      under oxidative stress from photoexcited titanium dioxide.
AB  - Superoxide dismutase (SOD)-deficient Escherichia coli was cultivated under the
      oxidative stress generated by photoexcited titanium dioxide. These cells showed
      higher growth rate and glucose consumption rate with accelerated accumulation of
      acetic acid in the medium, compared to the cells cultivated under the normal
      condition without the stress. Under the stress condition, the activity of acetate
      kinase and mRNA expressions of the enzymes for acetic acid production (pta and
      ackA) were approximately doubled, while the activity of citrate synthase and mRNA
      expressions of the enzymes in TCA cycle (gltA, acnA, icd, sucA, sucC, sdhA, fumA
      and mdh) were repressed by about half, as compared with those under the normal
      condition. These results suggest that the stress-suffering cells switch the
      metabolic pathway into a "suppressed aerobiosis", possibly for lowering the
      generation of reactive oxygen species.

PMID- 18338222
TI  - Visual exploration of structure-activity relationship using maximum common
      framework.
AB  - To help tracking all molecules made in a typical medicinal chemistry project, we
      have developed an algorithm to generate a maximum common framework (MCF)
      hierarchy and an interactive tool for its visualization and analysis. By
      identifying all unique frameworks for a set of molecules and all molecules
      containing each framework, we were able to simplify the MCF hierarchy build up
      steps and, as a result, speed up the entire process significantly. By allowing
      compounds to be assigned to multiple MCFs, users can easily remove bad branching
      nodes and concentrate on interesting ones. MCF hierarchies provide an effective
      and intuitive visualization for tracking medicinal chemistry lead optimization
      projects. We will provide examples to illustrate its usefulness.

PMID- 18338223
TI  - On the importance of topological descriptors in understanding structure-property
      relationships.
AB  - It has been generally observed in our work that molecular descriptors derived
      from a molecular graph theory or topological representation of structure play an
      important and often key role in many QSAR and QSPR models we have developed.
      These descriptors do not only provide the means to generate a good fit to the
      observed data used to train the models, but they also provide information that is
      needed to generate a clear physical interpretation of the underlying structure
      activity or property relationships. In addition, these descriptors provide a
      conformation-independent method of measuring the key features of molecular
      structure that affect the observed properties of the molecules. These
      characteristics are exemplified in a model developed to predict critical micelle
      concentration (CMC). A model is described that exhibits excellent predictive
      strength, is independent of conformation of the structures used, and that yields
      a great deal of detail regarding the underlying structure-property relationship
      driving the observed CMC.

PMID- 18338224
TI  - Predicting allergic contact dermatitis: a hierarchical structure-activity
      relationship (SAR) approach to chemical classification using topological and
      quantum chemical descriptors.
AB  - A hierarchical classification study was carried out based on a set of 70
      chemicals-35 which produce allergic contact dermatitis (ACD) and 35 which do not.
      This approach was implemented using a regular ridge regression computer code,
      followed by conversion of regression output to binary data values. The
      hierarchical descriptor classes used in the modeling include topostructural (TS),
      topochemical (TC), and quantum chemical (QC), all of which are based solely on
      chemical structure. The concordance, sensitivity, and specificity are reported.
      The model based on the TC descriptors was found to be the best, while the TS
      model was extremely poor.

PMID- 18338225
TI  - Differentiation of AmpC beta-lactamase binders vs. decoys using classification
      kNN QSAR modeling and application of the QSAR classifier to virtual screening.
AB  - The use of inaccurate scoring functions in docking algorithms may result in the
      selection of compounds with high predicted binding affinity that nevertheless are
      known experimentally not to bind to the target receptor. Such falsely predicted
      binders have been termed 'binding decoys'. We posed a question as to whether true
      binders and decoys could be distinguished based only on their structural chemical
      descriptors using approaches commonly used in ligand based drug design. We have
      applied the k-Nearest Neighbor (kNN) classification QSAR approach to a dataset of
      compounds characterized as binders or binding decoys of AmpC beta-lactamase.
      Models were subjected to rigorous internal and external validation as part of our
      standard workflow and a special QSAR modeling scheme was employed that took into
      account the imbalanced ratio of inhibitors to non-binders (1:4) in this dataset.
      342 predictive models were obtained with correct classification rate (CCR) for
      both training and test sets as high as 0.90 or higher. The prediction accuracy
      was as high as 100% (CCR = 1.00) for the external validation set composed of 10
      compounds (5 true binders and 5 decoys) selected randomly from the original
      dataset. For an additional external set of 50 known non-binders, we have achieved
      the CCR of 0.87 using very conservative model applicability domain threshold. The
      validated binary kNN QSAR models were further employed for mining the NCGC AmpC
      screening dataset (69653 compounds). The consensus prediction of 64 compounds
      identified as screening hits in the AmpC PubChem assay disagreed with their
      annotation in PubChem but was in agreement with the results of secondary assays.
      At the same time, 15 compounds were identified as potential binders contrary to
      their annotation in PubChem. Five of them were tested experimentally and showed
      inhibitory activities in millimolar range with the highest binding constant K(i)
      of 135 microM. Our studies suggest that validated QSAR models could complement
      structure based docking and scoring approaches in identifying promising hits by
      virtual screening of molecular libraries.

PMID- 18338226
TI  - Modeling dimerizations of transmembrane proteins using Brownian dynamics
      simulations.
AB  - The dimerizations of membrane proteins, Outer Membrane Phospholipase A (OMPLA)
      and glycophorin A (GPA), have been simulated by an adapted Brownian Dynamics
      program. To mimic the membrane protein environment, we introduced a hybrid
      electrostatic potential map of membrane and water for electrostatic interaction
      calculations. We added a van der Waals potential term to the force field of the
      current version of the BD program to simulate the short-range interactions of the
      two monomers. We reduced the BD sampling space from three dimensions to two
      dimensions to improve the efficiency of BD simulations for membrane proteins. The
      OMPLA and GPA dimers predicted by our 2D-BD simulation and structural refinement
      is in good agreement with the experimental structures. The adapted 2D-BD method
      could be used for prediction of dimerization of other membrane proteins, such as
      G protein-coupled receptors, to help better understanding of the structures and
      functions of membrane proteins.

PMID- 18338227
TI  - Editorial: special issue on "Evaluation of computational methods".

PMID- 18338228
TI  - Recommendations for evaluation of computational methods.
AB  - The field of computational chemistry, particularly as applied to drug design, has
      become increasingly important in terms of the practical application of predictive
      modeling to pharmaceutical research and development. Tools for exploiting protein
      structures or sets of ligands known to bind particular targets can be used for
      binding-mode prediction, virtual screening, and prediction of activity. A serious
      weakness within the field is a lack of standards with respect to quantitative
      evaluation of methods, data set preparation, and data set sharing. Our goal
      should be to report new methods or comparative evaluations of methods in a manner
      that supports decision making for practical applications. Here we propose a
      modest beginning, with recommendations for requirements on statistical reporting,
      requirements for data sharing, and best practices for benchmark preparation and
      usage.

PMID- 18338229
TI  - Simulation-based cheminformatic analysis of organelle-targeted molecules:
      lysosomotropic monobasic amines.
AB  - Cell-based molecular transport simulations are being developed to facilitate
      exploratory cheminformatic analysis of virtual libraries of small drug-like
      molecules. For this purpose, mathematical models of single cells are built from
      equations capturing the transport of small molecules across membranes. In turn,
      physicochemical properties of small molecules can be used as input to simulate
      intracellular drug distribution, through time. Here, with mathematical equations
      and biological parameters adjusted so as to mimic a leukocyte in the blood,
      simulations were performed to analyze steady state, relative accumulation of
      small molecules in lysosomes, mitochondria, and cytosol of this target cell, in
      the presence of a homogenous extracellular drug concentration. Similarly, with
      equations and parameters set to mimic an intestinal epithelial cell, simulations
      were also performed to analyze steady state, relative distribution and
      transcellular permeability in this non-target cell, in the presence of an apical
      to-basolateral concentration gradient. With a test set of ninety-nine monobasic
      amines gathered from the scientific literature, simulation results helped analyze
      relationships between the chemical diversity of these molecules and their
      intracellular distributions.

PMID- 18338230
TI  - Categorical QSAR models for skin sensitization based on local lymph node assay
      measures and both ground and excited state 4D-fingerprint descriptors.
AB  - In previous studies we have developed categorical QSAR models for predicting skin
      sensitization potency based on 4D-fingerprint (4D-FP) descriptors and in vivo
      murine local lymph node assay (LLNA) measures. Only 4D-FP derived from the ground
      state (GMAX) structures of the molecules were used to build the QSAR models. In
      this study we have generated 4D-FP descriptors from the first excited state
      (EMAX) structures of the molecules. The GMAX, EMAX and the combined ground and
      excited state 4D-FP descriptors (GEMAX) were employed in building categorical
      QSAR models. Logistic regression (LR) and partial least square coupled logistic
      regression (PLS-CLR), found to be effective model building for the LLNA skin
      sensitization measures in our previous studies, were used again in this study.
      This also permitted comparison of the prior ground state models to those
      involving first excited state 4D-FP descriptors. Three types of categorical QSAR
      models were constructed for each of the GMAX, EMAX and GEMAX datasets: a binary
      model (2-state), an ordinal model (3-state) and a binary-binary model (two-2
      state). No significant differences exist among the LR 2-state model constructed
      for each of the three datasets. However, the PLS-CLR 3-state and 2-state models
      based on the EMAX and GEMAX datasets have higher predictivity than those
      constructed using only the GMAX dataset. These EMAX and GMAX categorical models
      are also more significant and predictive than corresponding models built in our
      previous QSAR studies of LLNA skin-sensitization measures.

PMID- 18338232
TI  - Heavy metals concentration in soils of southeastern part of Ranga Reddy district,
      Andhra Pradesh, India.
AB  - There is a growing concern over the potential accumulation of heavy metals in
      soils owing to rapid industrial and urban development and increasing reliance on
      agrochemicals in the last several decades. These metals can infiltrate through
      the soil thereby causing groundwater pollution. Surface soil samples (5 to 15 cm)
      collected from southeastern part of Ranga Reddy district were analyzed for 14
      heavy metals (As, Ba, Co, Cr, Cu, Mo, Ni, Pb, Rb, Sr, V, Y, Zn and Zr) using
      Philips PW 2440 X-ray fluorescence spectrometer. Results for heavy and trace
      elements are reported for the first time in soils for this region. The
      contamination of the soils was assessed on the basis of enrichment factor (EF),
      geoaccumulation index (I (geo)), contamination factor and degree of
      contamination. The results reveal that variations in heavy element concentrations
      in the soil analyzed have both geogenic and anthropogenic contribution, due to
      the long period of constant human activities in the study area. The concentration
      of the metals Ba, Rb, Sr, V, Y and Zr were interpreted to be mainly inherited
      from parent materials (rocks) and the As, Co, Cr, Cu, Mo, Ni, Pb and Zn
      concentrations show contribution from geogenic and anthropogenic sources. The
      major element variations in soils are determined by the composition of the parent
      material predominantly involving granites.

PMID- 18338233
TI  - Human gut microbiota and bifidobacteria: from composition to functionality.
AB  - The human gut is the home of an estimated 10(18) bacterial cells, many of which
      are uncharacterized or unculturable. Novel culture-independent approaches have
      revealed that the majority of the human gut microbiota consists of members of the
      phyla Bacteroidetes and Firmicutes. Nevertheless the role of bifidobacteria in
      gut ecology illustrates the importance of Actinomycetes and other Actinobacteria
      that may be underestimated. The human gut microbiota represents an extremely
      complex microbial community the collective genome of which, the microbiome,
      encodes functions that are believed to have a significant impact on human
      physiology. The microbiome is assumed to significantly enhance the metabolism of
      amino and glycan acids, the turnover of xenobiotics, methanogenesis and the
      biosynthesis of vitamins. Co-colonisation of the gut commensals Bifidobacterium
      longum and Bacteroides thetaiotaomicron in a murine model system revealed that
      the presence of bifidobacteria induced an expansion in the diversity of
      polysaccharides targeted for degradation by Bacteroides and also induced host
      genes involved in innate immunity. In addition, comparative analysis of
      individual human gut microbiomes has revealed various strategies that the
      microbiota use to adapt to the intestinal environment while also pointing to the
      existence of a distinct infant and adult-type microbiota.

PMID- 18338234
TI  - The consequences of extended newborn screening programmes: do we know who needs
      treatment?
AB  - The development of an evidence base for newborn screening is especially difficult
      because of the rarity of disorders now detectable. One consequence of expanded
      newborn screening is that physicians are being called upon to manage asymptomatic
      babies with persistent biochemical disturbances that indicate likely enzyme
      deficiencies. Some of these may be very mild. There is not always agreement as to
      who should be treated. Particular problems are seen with disorders that were
      previously thought very rare but are now found frequently by newborn screening.
      Some of these disorders appear benign or nearly so, and in the present state of
      knowledge should clearly not be included in routine newborn screening panels.

PMID- 18338235
TI  - N-carbamylglutamate for neonatal hyperammonaemia in propionic acidaemia.
AB  - Hyperammonaemia is common in neonates with branched-chain organic acidaemias,
      primarily due to the inhibition of N-acetylglutamate (NAG) synthetase; NAG is an
      activator for carbamylphosphate synthetase I, the first enzyme of the urea cycle.
      N-Carbamylglutamate, a NAG analogue, has been reported to correct hyperammonaemia
      in neonates with organic acidaemias. It is, however, uncertain how the ammonia
      concentrations in these neonates would have progressed without the drug. We
      report a neonate with propionic acidaemia, whose plasma ammonia concentration
      responded dramatically to N-carbamylglutamate, having previously been over 950
      MUmol/L for 33 h. Our patient presented with poor feeding, hypoglycaemia,
      acidosis and hyperammonaemia (1044 MUmol/L at 65 h of age). The patient was
      treated with intravenous glucose (12 mg/kg per min), insulin, sodium benzoate,
      sodium phenylbutyrate, carnitine and continuous veno-venous haemofiltration
      (CVVH). In spite of these measures, the plasma ammonia concentration remained
      above 950 MUmol/L. After 30 h of CVVH, N-carbamylglutamate (250 mg/kg) was given
      through a nasogastric tube. Over the following 4 h, the plasma ammonia fell from
      1410 MUmol/L to 267 MUmol/L. Despite stopping CVVH, the ammonia level dropped to
      137 MUmol/L over the next 2 h and it continued to fall while the intravenous drug
      doses were reduced. The patient was readmitted, aged 4 weeks, with
      hyperammonaemia (347 MUmol/L) and again this responded to N-carbamylglutamate. In
      contrast, we report a previous patient with propionic acidaemia who showed no
      response to a lower dose of N-carbamylglutamate (25 mg/kg).

PMID- 18338236
TI  - Reversible defects on myocardial perfusion imaging early after coronary stent
      implantation: a predictor of late restenosis.
AB  - PURPOSE: If coronary artery was treated with optimal stent implantation,
      myocardial perfusion in the territory supplied by a dilated coronary artery
      should be not reversible. However, several studies have demonstrated reversible
      perfusion in the territory supplied by a coronary artery with an optimally
      implanted stent. The main objective of this study was to evaluate the incidence
      of reversible defects detected by M-SPECT early after optimal PTCA with stent
      implantation. Its second objective was to determine the predictive value of
      detecting reversible defects after stent implantation for late restenosis.
      METHODS: About 66 patients that underwent M-SPECT within 24 h of successful PTCA
      with stent implantation were included. All patients were followed up clinically
      and angiographically. The incidence of reversible perfusion defects on M-SPECT
      and the rate of late restenosis in target coronary arteries were evaluated
      retrospectively. RESULTS: Reversible perfusion defects on M-SPECT were observed
      in 26% of the patients and in 36% of lesions following successful PTCA with stent
      implantation. The incidence of late restenosis was significantly higher in
      patients and lesions with reversible perfusion defects (47% vs. 18%). According
      to binary logistic regression analysis, the presence of a reversible perfusion
      defects was the only independent predictor of late restenosis.

PMID- 18338237
TI  - The social epidemiologic concept of fundamental cause.
AB  - The goal of research in social epidemiology is not simply conceptual
      clarification or theoretical understanding, but more importantly it is to
      contribute to, and enhance the health of populations (and so, too, the people who
      constitute those populations). Undoubtedly, understanding how various individual
      risk factors such as smoking and obesity affect the health of people does
      contribute to this goal. However, what is distinctive of much on-going work in
      social epidemiology is the view that analyses making use of individual-level
      variables is not enough. In the spirit of Durkheim and Weber, S. Leonard Syme
      makes this point by writing that just "as bad water and food may be harmful to
      our health, unhealthful forces in our society may be detrimental to our capacity
      to make choices and to form opinions" conducive to health and well-being.
      Advocates of upstream (distal) causes of adverse health outcomes propose to
      identify the most important of these "unhealthful forces" as the fundamental
      causes of adverse health outcomes. However, without a clear, theoretically
      precise and well-grounded understanding of the characteristics of fundamental
      causes, there is little hope in applying the statistical tools of the health
      sciences to hypotheses about fundamental causes, their outcomes, and policies
      intended to enhance the health of populations. This paper begins the process of
      characterizing the social epidemiological concept of fundamental cause in a
      theoretically respectable and robust way.

PMID- 18338238
TI  - Validation of the French version of the colorectal-specific quality-of-life
      questionnaires EORTC QLQ-CR38 and FACT-C.
AB  - BACKGROUND: The aim of this study was to test the psychometric properties of the
      French version of the European Organization for Research and Treatment (EORTC)
      quality-of-life colorectal questionnaire (QLQ-CR38) and the functional assessment
      of cancer therapy-colorectal version 4 (FACT-C). METHOD: This prospective study
      included 209 patients with colorectal cancer: 71 undergoing chemotherapy, 56
      radiation, 15 surgery, and 67 survivors. Patients first completed in random order
      the FACT-C and the EORTC QLQ-CR38 and were asked if they had any preference for
      either questionnaire. The timing of administration of instruments differed
      according to patients' treatment to better assess psychometric properties.
      RESULTS: The FACT-C showed good acceptability, good reproducibility and excellent
      internal consistency. The QLQ-CR38 had lower internal consistency. Patients did
      not express a preference for one survey over another. CONCLUSION: This study
      confirms the value of the FACT-C and suggests some limits of the QLQ-CR38 for
      patients with colorectal cancer.

PMID- 18338239
TI  - Predictors of choosing life-long screening or prophylactic surgery in women at
      high and moderate risk for breast and ovarian cancer.
AB  - The aim of this study is to summarize published empirical data describing the
      predictors of adhering to screening practices and choosing to have prophylactic
      surgery in women at increased risk for breast and ovarian cancer. Pubmed,
      Psychinfo and Cinahl databases were searched to identify studies on the
      predictors of adherence to breast and ovarian cancer screening and predictors of
      having a prophylactic mastectomy or salpingo-oophorectomy. We found 37 empirical
      studies that met our inclusion criteria. The main predictors of the use of
      preventive measures are related to DNA test results, socio-demographic
      characteristics, and psychological outcome measures. It is concluded that there
      is no unequivocal relationship between age, education, risk perception, or
      anxiety and adherence to breast and ovarian cancer screening practices. Worrying
      about cancer is associated with a higher adherence to screening practices.

PMID- 18338240
TI  - Intradermal injection of Hsp60 induces cytokine responses in canine atopic and
      healthy skin.
AB  - The purpose of this study was to investigate the immunoregulatory potential of
      Hsp60 in the skin of dogs with atopic dermatitis. Three dogs with chronic atopic
      dermatitis and four healthy dogs were injected intradermally with Hsp60 and
      phosphate-buffered saline. Biopsies were taken before testing from non-injected
      control skin, lesional and non-lesional atopic skin, and 48 and 72 h after
      injection. Analysis of cytokine messenger RNA was performed using quantitative
      real-time polymerase chain reaction. Forty-eight hours after Hsp60 injection, a
      rise in interleukin (IL)-10 was found (P = 0.034) with the highest expression
      levels in non-lesional atopic and control skin. A rise of transforming growth
      factor beta (P = 0.015) and IL-12p40 (P = 0.017) was noticed 72 h after Hsp60
      injection in control skin. No significant differences were observed for the
      expression of IL-4, IL-12p35, and interferon gamma. The results indicate that
      Hsp60 is able to induce cytokines of a regulatory and Th1 phenotype in the skin.
      Furthermore, this study seems to provide a first indication of deficient Hsp60
      response in atopic dermatitis affected skin.

PMID- 18338241
TI  - Development of stable influenza vaccine powder formulations: challenges and
      possibilities.
AB  - Influenza vaccination represents the cornerstone of influenza prevention.
      However, today all influenza vaccines are formulated as liquids that are unstable
      at ambient temperatures and have to be stored and distributed under
      refrigeration. In order to stabilize influenza vaccines, they can be brought into
      the dry state using suitable excipients, stabilizers and drying processes. The
      resulting stable influenza vaccine powder is independent of cold-chain
      facilities. This can be attractive for the integration of the vaccine logistics
      with general drug distribution in Western as well as developing countries. In
      addition, a stockpile of stable vaccine formulations of potential vaccines
      against pandemic viruses can provide an immediate availability and simple
      distribution of vaccine in a pandemic outbreak. Finally, in the development of
      new needle-free dosage forms, dry and stable influenza vaccine powder
      formulations can facilitate new or improved targeting strategies for the vaccine
      compound. This review represents the current status of dry stable inactivated
      influenza vaccine development. Attention is given to the different influenza
      vaccine types (i.e. whole inactivated virus, split, subunit or virosomal
      vaccine), the rationale and need for stabilized influenza vaccines, drying
      methods by which influenza vaccines can be stabilized (i.e. lyophilization, spray
      drying, spray-freeze drying, vacuum drying or supercritical fluid drying), the
      current status of dry influenza vaccine development and the challenges for
      ultimate market introduction of a stable and effective dry-powder influenza
      vaccine.

PMID- 18338242
TI  - IL-17 producing gammadelta T cells are required for a controlled inflammatory
      response after bleomycin-induced lung injury.
AB  - BACKGROUND: gammadelta T cells play a key role in the regulation of inflammatory
      responses in epithelial tissue, and in adaptive immunity, as gammadelta T cell
      deficient mice have a severely impaired capacity to clear lung pathogens.
      gammadelta T cells regulate the initial inflammatory response to microbial
      invasion and thereby protect against tissue injury. Here we examined the response
      of gammadelta T cells to lung injury induced by bleomycin, in an effort to study
      the inflammatory response in the absence of any adaptive immune response to a
      pathogen. RESULTS: After lung injury by bleomycin, we localized the gammadelta T
      cells to the lung lesions. gammadelta T cells were the predominant source of IL
      17 (as detected by flow cytometry and real-time PCR). Moreover, gammadelta T cell
      knockout mice showed a significant reduction in cellular infiltration into the
      airways, reduced expression of IL-6 in the lung, and a significant delay in
      epithelial repair. CONCLUSION: Mouse gammadelta T cells produce IL-17 in response
      to lung injury and are required for an organized inflammatory response and
      epithelial repair. The lack of gammadelta T cells correlates with increased
      inflammation and fibrosis.

PMID- 18338243
TI  - Beyond conventional event-related brain potential (ERP): exploring the time
      course of visual emotion processing using topographic and principal component
      analyses.
AB  - Recent technological advances with the scalp EEG methodology allow researchers to
      record electric fields generated in the human brain using a large number of
      electrodes or sensors (e.g. 64-256) distributed over the head surface (multi
      channel recording). As a consequence, such high-density ERP mapping yields fairly
      dense ERP data sets that are often hard to analyze comprehensively or to relate
      straightforwardly to specific cognitive or emotional processes, because of the
      richness of the recorded signal in both the temporal (millisecond time
      resolution) and spatial (multidimensional topographic information) domains.
      Principal component analyses (PCA) and topographic analyses (combined with
      distributed source localization algorithms) have been developed and successfully
      used to deal with this complexity, now offering powerful alternative strategies
      for data-driven analyses in complement to more traditional ERP analyses based on
      waveforms and peak measures. In this paper, we first briefly review the basic
      principles of these approaches, and then describe recent ERP studies that
      illustrate how they can inform about the precise spatio-temporal dynamic of
      emotion processing. These studies show that the perception of emotional visual
      stimuli may produce both quantitative and qualitative changes in the electric
      field configuration recorded at the scalp level, which are not apparent when
      using conventional ERP analyses. Additional information gained from these
      approaches include the identification of a sequence of successive processing
      stages that may not fully be reflected in ERP waveforms only, and the segregation
      of multiple or partly overlapping neural events that may be blended within a
      single ERP waveform. These findings highlight the added value of such alternative
      analyses when exploring the electrophysiological manifestations of complex and
      distributed mental functions, as for instance during emotion processing.

PMID- 18338244
TI  - Generating controlled image sets in cognitive neuroscience research.
AB  - The investigation of perceptual and cognitive functions with non-invasive brain
      imaging methods critically depends on the careful selection of stimuli for use in
      experiments. For example, it must be verified that any observed effects follow
      from the parameter of interest (e.g. semantic category) rather than other low
      level physical features (e.g. luminance, or spectral properties). Otherwise,
      interpretation of results is confounded. Often, researchers circumvent this issue
      by including additional control conditions or tasks, both of which are flawed and
      also prolong experiments. Here, we present some new approaches for controlling
      classes of stimuli intended for use in cognitive neuroscience, however these
      methods can be readily extrapolated to other applications and stimulus
      modalities. Our approach is comprised of two levels. The first level aims at
      equalizing individual stimuli in terms of their mean luminance. Each data point
      in the stimulus is adjusted to a standardized value based on a standard value
      across the stimulus battery. The second level analyzes two populations of stimuli
      along their spectral properties (i.e. spatial frequency) using a dissimilarity
      metric that equals the root mean square of the distance between two populations
      of objects as a function of spatial frequency along x- and y-dimensions of the
      image. Randomized permutations are used to obtain a minimal value between the
      populations to minimize, in a completely data-driven manner, the spectral
      differences between image sets. While another paper in this issue applies these
      methods in the case of acoustic stimuli (Aeschlimann et al., Brain Topogr 2008),
      we illustrate this approach here in detail for complex visual stimuli.

PMID- 18338245
TI  - Mapping the semantic homunculus: a functional and behavioural analysis of overt
      semantic generation.
AB  - Previous neuroanatomical research has shown that semantic processing of action
      related language activates the premotor, motor, and sensory cortices
      somatotopically (e.g., Tettamanti et al., J Cognitive Neurosci. 2005;17(2): 273
      281, using a listening task, and Hauk et al., Neuron. 2004;41:301-307 and
      Pulvermuller et al., Eur J Neurosci 2005;21:793-797; J Cognitive Neurosci
      2005;17(6):884-892 using a silent reading task). We examined this somatotopic
      semantics hypothesis using an overt semantic generation task (i.e., participants
      generated aloud their own personal description of how they would interact with
      target object words), rather than semantic comprehension as examined in previous
      research, so as to provide a stronger test of the hypothesis under conditions
      that tap one's own semantic knowledge about interacting with objects. Experiment
      1 used functional Magnetic Resonance Imaging (fMRI) to examine somatotopically
      organized activation in the premotor cortex for an overt semantic generation
      task, using targets that naturally involve either arm interactions or leg
      interactions. Consistent with previous research, our results showed that semantic
      processing related to object interaction involves the motor, premotor and sensory
      cortices in a somatotopic fashion. Previous behavioural research has shown a
      response advantage in lexical decision for words with multiple meanings or
      features, which diminishes with tasks that decrease semantic involvement (e.g.,
      Borowsky and Masson, J Exp Psychol: Learn Memory Cognit 1996; 22(1):63-85; Pexman
      et al., Psychon Bull Rev 2002;9(3): 542-549). Experiment 2 evaluated whether
      semantic generation response times (total duration of response) display a
      complexity advantage (i.e., faster response times for more complex objects), and
      whether complexity ratings were related to the volume of brain activation during
      the task. Results from this behavioural experiment revealed a significant
      negative relationship between the total duration of response (i.e., the total
      amount of time taken to respond to the stimuli) and object complexity for leg
      objects (a semantic complexity advantage), but not for arms. This suggests that
      the smaller repertoire of possible interactions with leg objects requires a
      greater reliance on semantic knowledge in order to respond in the semantic
      generation task. This interpretation was further supported by a greater volume of
      brain activation in the premotor cortex for arm objects versus leg objects. The
      response times from Experiment 1 were also compared to the semantic complexity
      ratings gathered in Experiment 2 to determine if response times in the fMRI
      environment were affected by how complex an object is.

PMID- 18338246
TI  - Perfectionism and peer relations among children with obsessive-compulsive
      disorder.
AB  - The study examined perfectionism, symptoms of obsessive-compulsive disorder (OCD)
      and depression, and peer relationships among a clinical sample of 31 youth (age
      range 7-18 years) diagnosed with OCD. Using a correlational design,
      perfectionistic beliefs accounted for significant variance in OCD symptoms,
      depressive symptoms, and difficulties in peer relationships for children with
      OCD. One dimension of perfectionism, sensitivity to mistakes, was the most
      salient maladaptive aspect of perfectionism for this sample whereas another
      dimension, contingent self-esteem, emerged as the most salient adaptive
      dimension. Implications are discussed regarding the diagnosis, treatment, and
      developmental course of OCD among children and adolescents.

PMID- 18338247
TI  - Estrogen regulated gene expression in response to neoadjuvant endocrine therapy
      of breast cancers: tamoxifen agonist effects dominate in the presence of an
      aromatase inhibitor.
AB  - Estrogens (E) and estrogen receptors (ER) are implicated in breast cancer growth
      and are targets of hormonal therapies. Such therapies commonly use aromatase
      inhibitors (AI) to block E production, or antiestrogens like tamoxifen (TAM),
      which targets ER. Here we compare genes in pre-and post-treatment tumor pairs of
      patients with ER+ tumors, that were treated preoperatively with the AI exemestane
      alone, or with exemestane plus TAM. The accompanying manuscript shows that tumors
      from patients treated with AI + TAM responded less well than tumors treated with
      AI alone. The present manuscript defines the E-signaling mechanisms underlying
      these differences, and describes genetic differences between hormone responsive
      versus intrinsically resistant ER+ tumors. Gene expression profiling was
      performed on paired tumor biopsies of individual patients before treatment, and
      after 4 months of treatment with AI or AI + TAM. Separately, E and TAM regulated
      genes were defined using a human breast cancer xenograft model. We demonstrate:
      (1) that AI alone alters global gene expression approximately 5 times more than
      AI + TAM, and is 11 times more effective in modifying expression of E regulated
      genes; (2) among E regulated genes, there is little overlap between AI and AI +
      TAM treatment groups. AI + TAM preferentially induce genes, like androgen
      receptors, expressing TAM "E-like" agonist activity, or genes uniquely regulated
      by TAM. (3) A pre-treatment 25 gene signature of ER+ tumors may predict response
      or intrinsic resistance to endocrine therapies. We conclude that in the presence
      of exemestane, the agonist properties of TAM are paradoxically exposed,
      diminishing the effectiveness of combination therapy.

PMID- 18338248
TI  - Renal expression of the brain and muscle isoforms of glycogen phosphorylase in
      different cell types.
AB  - Kidney contains glycogen. Glycogen is degraded by glycogen phosphorylase (GP).
      This enzyme comes in three isoforms, one of which, the brain isozyme (GP BB), is
      known to occur in kidney. Its pattern of distribution in rat kidney was studied
      in comparison to that of the muscle isoform (GP MM) with the aim to see if for GP
      BB and GP MM there were functional similarities in brain and kidney. In
      immunoblotting and quantitative reverse transcriptase polymerase chain reaction
      (RT-PCR) experiments, both isozymes and their respective mRNAs were found in
      kidney homogenates. GP BB was immunocytochemically detected in collecting ducts
      which were identified by the marker protein aquaporin-2. GP MM was localized
      exclusively in interstitial cells of cortex and outer medulla. These cells were
      identified as fibroblasts by their expression of 5'-ectonucleotidase (cortex) or
      by their morphology (outer medulla). The physiological role of both isozymes is
      discussed in respect to local demands of energy and of proteoglycan building
      blocks.

PMID- 18338249
TI  - Transcription factor GATA-3 regulates the transcriptional activity of dopamine
      beta-hydroxylase by interacting with Sp1 and AP4.
AB  - GATA-3 is a zinc finger transcription factor that is expressed in T cell lineages
      as well as in the nervous system during development. In this study, we report
      that forced expression of GATA-3 resulted in an increased number of dopamine beta
      hydroxylase (DBH)-expressing neurons in primary neural crest stem cell (NCSC)
      culture, suggesting that the DBH gene may be a downstream target gene of GATA-3.
      GATA-3 robustly transactivates the promoter function of the noradrenaline (NA)
      synthesizing DBH gene, via two specific upstream promoter domains; one at -62 to 
      32 bp and the other at -891 to -853 bp. Surprisingly, none of these domains
      contain GATA-3 binding sites but encompass binding motifs for transcription
      factors Sp1 and AP4, respectively. Protein-protein interaction analyses both in
      vitro and in vivo and chromatin immunoprecipitation (ChIP) assays showed that
      GATA-3 effects its transcriptional regulatory function through physical
      interactions with these transcription factors.

PMID- 18338250
TI  - Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein
      kinase-A.
AB  - Protein kinase A (PKA) plays a crucial role in tau hyperphosphorylation, an early
      event of Alzheimer disease (AD), and 17beta-estradiol replacement in aging women
      forestalls the onset of AD. However, the role of estradiol in PKA-induced tau
      hyperphosphorylation is not known. Here, we investigated the effect of 17beta
      estradiol on cAMP/PKA activity and the PKA-induced tau hyperphosphorylation in
      HEK293 cells stably expressing tau441. We found that 17beta-estradiol effectively
      attenuated forskolin-induced overactivation of PKA and elevation of cAMP, and
      thus prevented tau from hyperphosphorylation. These data provide the first
      evidence that 17beta-estradiol can inhibit PKA overactivation and the PKA-induced
      tau hyperphosphorylation, implying a preventive role of 17beta-estradiol in AD
      like tau pathology.

PMID- 18338251
TI  - Role of inhibitor of apoptosis proteins and Smac/DIABLO in staurosporine-induced
      cerebellar granule neurons death.
AB  - Apoptosis is characterized by morphological and biochemical alterations mediated
      by caspases. The Inhibitor of Apoptosis Proteins (IAP) comprises a family of
      proteins that regulate apoptosis by inhibiting caspases. IAP are controlled by
      different mechanisms including transcriptional regulation, ubiquitination and
      interaction with proapoptotic proteins such as Smac/DIABLO. Here, we evaluated
      the role of IAP and Smac/DIABLO in neuronal death. We used cultured rat
      cerebellar granule neurons (CGN) under conditions that induce apoptosis
      (staurosporine). We found the expression of cIAP-1, cIAP-2, XIAP and survivin,
      but not BRUCE in CGN under survival conditions. When CGN were treated with
      staurosporine we detected a decrease in cIAP-1 and cIAP-2, but not in XIAP and
      survivin levels. Under these conditions Smac/DIABLO was released from the
      mitochondria suggesting its involvement in staurosporine-induced death of CGN.
      However, the Smac N7 peptide, which interacts with caspase-9 binding site in
      XIAP, did not show any effect on CGC viability.

PMID- 18338252
TI  - WITHDRAWN: Use of PSA-NCAM in Repair of the Central Nervous System.
AB  - Polysialic acid (PSA) is a highly hydrated polymer whose presence at the cell
      surface can reduce cell interactions, and thereby increase tissue and cellular
      plasticity. Given its ability to create a permissive environment for cell
      migration and axonal growth, the potential of engineered over-expression of PSA
      to promote tissue repair has been explored in the adult CNS. Several promising
      results have been obtained that suggest that PSA engineering may become a
      valuable therapeutic tool.

PMID- 18338253
TI  - Two novel ergtoxins, blockers of K+-channels, purified from the Mexican scorpion
      Centruroides elegans elegans.
AB  - Voltage-gated potassium channels of the ether-a-go-go related gene (ERG) family
      are implicated in many important cellular processes. Three such genes have been
      cloned (erg1, erg2 and erg3) and shown to be expressed in the central nervous
      system (CNS) of mammalians. This communication describes the isolation and
      characterization of two isoforms of scorpion toxin (CeErg4 and CeErg5, systematic
      nomenclature gamma-KTx1.7 and gamma-KTx1.8, respectively) that can discriminate
      the various subtypes of ERG channels of human and rat. These peptides were
      purified from the venom of the Mexican scorpion Centruroides elegans elegans.
      They contain 42 amino acid residues, tightly folded by four disulfide bridges.
      Both peptides block in a reversible manner human and rat ERG1 channels, but have
      no effect on human ERG2. They also block completely and irreversibly the rat ERG2
      and the human ERG3 channels hence are excellent tools for the discrimination of
      the various sub-types of ion-channels studied.

PMID- 18338254
TI  - Artepillin C derived from propolis induces neurite outgrowth in PC12m3 cells via
      ERK and p38 MAPK pathways.
AB  - We investigated whether artepillin C, a major component of Brazilian propolis,
      acts as a neurotrophic-like factor in rat PC12m3 cells, in which nerve growth
      factor (NGF)-induced neurite outgrowth is impaired. When cultures of PC12m3 cells
      were treated with artepillin C at a concentration of 20 microM, the frequency of
      neurite outgrowth induced by artepillin C was approximately 7-fold greater than
      that induced by NGF alone. Artepillin C induced-neurite outgrowth of PC12m3 cells
      was inhibited by the ERK inhibitor U0126 and by the p38 MAPK inhibitor SB203580.
      Although artepillin C-induced p38 MAPK activity was detected in PC12m3 cells,
      phosphorylation of ERK induced by artepillin C was not observed. On the other
      hand, artepillin C caused rapid activation of ERK and the time course of the
      activation was similar to that induced by NGF treatment in PC12 parental cells.
      However, NGF-induced neurite outgrowth was inhibited by artepillin C treatment.
      Interestingly, inhibition of ERK by U0126 completely prevented artepillin C
      induced p38 MAPK phosphorylation of PC12m3 cells. These findings suggest that
      artepillin C-induced activation of p38 MAPK through the ERK signaling pathway is
      responsible for the neurite outgrowth of PC12m3 cells.

PMID- 18338255
TI  - Kalirin-7, a protein enriched in postsynaptic density, is involved in ischemic
      signal transduction.
AB  - Regulators of mitogen activated protein kinases (MAPK) and c-Jun N
      terminal/stress-activated kinase (JNK) include Rho-like small GTP-binding
      proteins and their regulators. SynGAP and kalirin-7 are postsynaptic density
      enriched proteins identified through their interaction with Rho GTPases and PSD
      95 scaffold protein. We examined immunoreactivity of SynGAP, kalirin-7, and PSD
      95, phosphorylation of MAPK and JNK in control and postischemic hippocampus in
      gerbil model of transient forebrain ischemia. In normal brain higher amount of
      kalirin-7 but a lower amount of P-JNK was found in ischemia-resistant hippocampal
      area: CA2-3, DG than in ischemia-vulnerable CA1. After 5 min ischemia and 1 h
      reperfusion a decrease of P-ERK and increase of P-JNK were uniformly observed in
      the hippocampal parts. By contrast, the amount of kalirin-7 in CA2-3, DG reached
      56% (P < 0.001) of control while was doubled in CA1. Oppositely, the
      immunoreactivity of SynGAP was increased in CA2-3, DG and reduced in CA1. Our
      data indicate that SynGAP and kalirin-7 take part in the regulation of ischemic
      signal transduction but the mechanism does not seem directly connected with the
      activation of MAPK and JNK.

PMID- 18338257
TI  - A portrait of the neurochemist as a young man: a memoir.

PMID- 18338258
TI  - Effects of cyclohexanonic long-chain fatty alcohol, tCFA15 on amino acids in
      diabetic rat brain: a preliminary study.
AB  - The aim of this study was to evaluate the effects of streptozotocin-induced type
      1diabetes and a subchronic treatment with cyclohexanonic long-chain fatty
      alcohol, 3-(15-hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (tCFA15) on
      contents of amino acids including aspartate, glutamate, glutamine, GABA, glycine,
      taurine, alanine, serine, threonine, and arginine in the prefrontal cortex,
      hippocampus and striatum. Levels of glutamate, threonine, taurine, alanine,
      arginine, and the ratio of glutamate/glutamine were altered region-differently in
      the brain of diabetic rats. However, tCFA15 region-specifically antagonized the
      changes in taurine and arginine levels and the ratio of glutamate/glutamine. The
      alteration in glutamate/glutamine ratio may indicate that experimental models of
      type 1 diabetes have abnormalities of neuron-gria interaction in brain.

PMID- 18338259
TI  - WITHDRAWN: Dendritic Spine and Synapse Morphological Alterations Induced by a
      Neural Cell Adhesion Molecule (NCAM) Mimetic.
AB  - The neural cell adhesion molecule (NCAM) is a glycoprotein expressed on the
      surface of neurons and glial cells. It plays a key role in morphogenesis of the
      nervous system, regeneration of damaged neural tissue and synaptic plasticity.
      The extracellular domain of NCAM engages in homophilic interactions (NCAM binding
      to NCAM) and in heterophilic interactions between NCAM and other proteins such as
      the fibroblast growth factor (FGF) receptor. It promotes synaptogenesis and
      activity-dependent remodelling of synapses but less is know of its influence on
      synaptic and dendritic morphology. Recently, quantitative electron microscopy and
      3-dimensional reconstruction (3-D) of ultrathin serial sections has been used to
      examine the morphology of synapses and dendritic spines in the hippocampus of
      rats treated with a neural cell adhesion molecule-derived fibroblast growth
      factor receptor agonist, FGL-peptide (an NCAM mimetic). These data show clearly
      that the FGL peptide has marked influences on both spine and synaptic form.

PMID- 18338260
TI  - Activation of calpain, cathepsin-b and caspase-3 during transient focal cerebral
      ischemia in rat model.
AB  - Calpains, cathepsins and caspases play crucial role in mediating cell death. In
      the present study we observed a cascade of events involving the three proteases
      during middle cerebral artery occlusion (MCAo) in Wistar rats. The rats were MCA
      occluded and reperfused at various time points. We observed a maximal increase in
      the levels of calpains during 1h and 12 h after reperfusion than permanently
      occluded rats. Further, these levels were reduced by 1st and 3rd day of
      reperfusion. Similarly the cathepsin-b levels were significantly increased during
      1h and 12 h, of reperfusion, followed by activation of caspase-3 which reached
      maximal levels by 1st and 3rd day of reperfusion. The sequential activation of
      calpains, cathepsin-b and cleaved caspase-3 is evident by the Western blot
      analysis which was further confirmed by the cleavage of substrates like PSD-95
      and spectrin. The differences in the regional distribution and elevation of these
      proteases at different reperfusion time periods indicates that differential mode
      of cell death occur in the brain during cerebral ischemia in rat model.

PMID- 18338261
TI  - Interleukin-10 (-819 C/T) and TNF-A (-308 G/A) as risk factors for H. pylori
      associated gastric MALT-lymphoma.

PMID- 18338262
TI  - Gastroduodenal artery aneurysm bleeding mimicking hemobilia: a case report.

PMID- 18338263
TI  - Intramuscular neostigmine and glycopyrrolate safely accelerated bowel evacuation
      in patients with spinal cord injury and defecatory disorders.
AB  - Difficulty with evacuation after spinal cord injury (SCI) may be due to a lack of
      parasympathetic stimulation of the colon. Prior studies in persons with spinal
      cord injury have suggested that intravenous administration of neostigmine
      stimulates colonic motility while glycopyrrolate attenuates some of the
      cholinergic side effects of neostigmine. We thus performed a double-blind, cross
      over study to evaluate the effect of neostigmine/glycopyrrolate injections in
      patients with SCI and defecatory difficulties. Seven subjects received active
      treatment (neostigmine 2 mg and glycopyrrolate 0.4 mg intramuscularly) during
      three consecutive bowel evacuation sessions and were crossed-over to placebo
      injections for three consecutive sessions. Compared with placebo,
      neostigmine/glycopyrrolate reduced the total bowel evacuation time from 98.1 +/-
      7.2 to 74.8 min +/- 5.8 (p < 0.05). The lowest heart rate or blood pressure was
      not significantly different between the treatment and placebo groups. In
      conclusion, neostigmine/glycopyrrolate may improve bowel evacuation in patients
      with SCI-related defecatory disorders.

PMID- 18338264
TI  - Reactive oxygen species and the hypomotility of the gall bladder as targets for
      the treatment of gallstones with melatonin: a review.
AB  - Free radical-mediated damage of the gall bladder epithelium predisposes to the
      development of both gall bladder inflammation and gallstone formation, which
      often coexist. Melatonin, a pineal and gut secretory product, due to its
      antioxidant activity along with its effect on the aging gall bladder myocytes,
      inhibits gallstone formation. Melatonin reduces the biliary levels of cholesterol
      by inhibiting cholesterol absorption across the intestinal epithelium and by
      increasing the conversion of cholesterol to bile acids. The incidence of
      gallstones is increasing and is expected to rise dramatically with the increase
      in the longevity and the risk factors such as obesity. The change in the
      prevalence of cholelithiasis is associated with a proportionate rise in the
      incidence of cholangiocarcinoma. In an attempt to improve the quality of life of
      the rapidly increasing aging population, this article reviews up-to-date
      information on the pathophysiology of the gall bladder function and discusses the
      development of new therapies with potential good patient compliance and lower
      cost than the current treatments.

PMID- 18338265
TI  - Natural history and long-term clinical behavior of segmental colitis associated
      with diverticulosis (SCAD syndrome).
AB  - Localized inflammation of the sigmoid colon or segmental colitis associated with
      diverticulosis (SCAD syndrome) is an increasingly recognized, apparently
      uncommon, clinical and pathological disorder usually described in older adults.
      In the present study, 24 symptomatic patients, including 14 males, (58.3%) and 10
      females (41.7%) were evaluated over a 20-year period with follow-up intervals
      ranging from 2 to 16 years. In most, initial clinical symptoms appeared after age
      40 years and included rectal bleeding, diarrhea, and abdominal pain. Most (21 of
      24, over 80%) initially responded with long-term resolution of their disease
      after treatment only with a 5-aminosalicylate. In addition, however, spontaneous
      remissions without any form of drug therapy were documented. In some, persistent,
      chronically active disease or true episodic recurrences were seen, leading to use
      of corticosteroids and/or resective surgery. Evidence here also suggested that
      colonic neoplasia, including adenoma development and cancer, were not related to
      the presence of this uniquely localized mucosal inflammatory process defined
      within the sigmoid colon. This study documents the natural history and long-term
      clinical behavior of this unusual segmental inflammatory process, associated with
      diverticulosis, and provides additional strong evidence that the SCAD syndrome is
      very distinct and can be readily separated from other forms of chronic
      inflammatory bowel disease.

PMID- 18338266
TI  - The effects of hyperprolactinemia on bone and fat.
AB  - Many patients with prolactin secreting pituitary tumors have decreased bone
      mineral. The bone loss is associated with an increase in bone resorption and is
      secondary to prolactin-induced hypogonadism. In both sexes trabecular bone in the
      spine and hip is more affected than cortical bone in the distal radius.
      Normalization of prolactin and restoration of gonadal function increases bone
      density but is not associated with normalization of bone mass. It is not known
      whether the bone loss in hyperprolactinemic subjects represents a failure to
      achieve peak bone mass or is due to accelerated bone loss. Despite low bone
      density hyperprolactinemic subjects do not demonstrate increased fractures. The
      association between prolactin, weight gain and obesity suggests that prolactin
      may also be a modulator of body composition and body weight. It is not known
      whether hyperprolactinemia associated weight gain is due to stimulation of
      lipogenesis or due to disruption of central nervous system dopaminergic tone.
      Hyperprolactinemia is also associated with insulin resistance and endothelial
      dysfunction which may improve after normalization of prolactin. The clinical
      significance of these findings and the precise role of prolactin in regulation of
      weight and metabolism remain to be elucidated.

PMID- 18338267
TI  - Preoperative assessment for pituitary surgery.
AB  - Evaluation of pituitary function is essential before pituitary surgery. In
      hyperprolactinaemic patients with a pituitary macrolesion, tumoral secretion of
      prolactin must be distinguished from 'disconnection' hyperprolactinaemia; serum
      prolactin >200 mcg/l is virtually diagnostic of a macroprolactinoma whereas
      levels <80 mcg/l usually indicate 'disconnection'. The prolactin 'hook effect'
      should be excluded. A minimum set of pre-operative endocrine tests should include
      serum electrolytes, cortisol (at 08.00-09.00 h), free-T4, TSH, prolactin,
      oestradiol/testosterone, LH, FSH and IGF-1. Some clinicians will choose to
      perform pre-operative Synacthen or insulin tolerance testing to further define
      ACTH reserve. If basal cortisol, Synacthen or insulin tolerance test results are
      abnormal, steroid supplementation is indicated for at least the first 48 h after
      surgery. If pre-operative basal cortisol is <100 nmol/l, replacement steroids
      should be continued until the time of post-operative pituitary function testing
      (6-8 weeks after surgery). In patients with pre-operative basal cortisol >450
      nmol/l, peri-operative glucocorticoid replacement is unnecessary and further
      cortisol levels should be checked a few days after surgery. Most clinicians defer
      detailed evaluation of growth hormone reserve until after surgery. Diabetes
      insipidus is rarely a problem before surgery in patients with pituitary adenomas
      but may occur post-operatively. Close co-operation between anesthetic, endocrine
      and surgical teams is strongly recommended.

PMID- 18338268
TI  - Increased GABA B receptor subtype expression in the nucleus of the solitary tract
      of the spontaneously hypertensive rat.
AB  - Expression of GABA(B) receptor messenger RNA (mRNA) in the central nervous system
      was compared between the spontaneously hypertensive (SHR) and normotensive Wistar
      Kyoto (WKY) rat. Polymerase chain reaction (PCR) revealed all the isoforms except
      B1e in cortex, hypothalamus, and medulla oblongata. In the nucleus of the
      solitary tract (NTS) and ventrolateral medulla (VLM), the B1a-c and 1 g isoforms
      were present as well as B2. Real-time PCR detected significantly higher levels of
      B1a (p < 0.01) and B2 (p < 0.05) mRNA in the NTS of SHR compared to WKY. A
      significant increase in B1a expression (p < 0.05) was detected in VLM.
      Immunolabeling suggested presynaptic and postsynaptic expression of B1a, B1b, and
      B2 subtypes throughout the NTS, with significant differences in distribution
      patterns and labeling between subtypes and between SHR and WKY. These findings
      suggest that GABA(B) receptors expressed by neurones in NTS may be involved in
      cardiovascular regulation and that changes in GABA(B) mRNA expression levels may
      contribute to the hypertensive state in SHR.

PMID- 18338269
TI  - Massive tongue swelling in refractory status epilepticus treated with high-dose
      pentobarbital.
AB  - INTRODUCTION: The potential causes of acquired macroglossia are extensive. The
      authors report two cases of subacute marked tongue swelling resulting in airway
      compromise in patients with refractory status epilepticus requiring prolonged
      pentobarbital coma. METHOD: The hospitalization histories of the reported
      patients were retrospectively reviewed. RESULT: The tongue swelling completely
      resolved in one case and significantly improved in the other after
      discontinuation of pentobarbital infusion or switching to phenobarbital. The
      authors speculate that the causes were multifarious, likely a combination of
      localized angioedema due to barbiturate vehicle and triggered by an initial
      tongue bite. CONCLUSION: Progressive tongue swelling causing airway obstruction
      can occur well beyond the acute phase of status epilepticus and may potentially
      cause problems with extubation in nontracheotomized patients.

PMID- 18338270
TI  - Autonomic control of the aging heart.
AB  - Cardiovascular diseases including hypertension, myocardial infarction, stroke,
      and heart failure continue to account for the majority of deaths in the developed
      world. Whilst the incidence of these clinical disorders does increase with age,
      outcomes in affected patients tend to be disproportionately adverse with
      advancing years. In this context it is important to understand the various
      compensatory processes which become activated in cardiovascular disease. In
      particular, the autonomic nervous system is known to play a key pathogenic role
      in the cause and response to many of these conditions. The normal aging process
      is accompanied by a complex series of changes in the autonomic control of the
      cardiovascular system, favoring heightened cardiac sympathetic tone with
      parasympathetic withdrawal and blunted cardiovagal baroreflex sensitivity.
      Together these changes have the potential to further magnify the effects of
      concomitant cardiovascular disease. Attention to the mechanisms of these changes
      and the development of appropriate therapies may serve to reduce the added
      influence of age on outcome in patients experiencing cardiovascular disease.

PMID- 18338271
TI  - Vitamin D(3) in fat tissue.
AB  - The literature describing vitamin D content of fat tissue is extremely limited.
      We conducted a pilot study that measured the concentrations of vitamin D(3) in
      the fat tissue and serum of obese adults. These measurements were performed using
      a new liquid chromatography mass spectrometry (LC/MS) method. The objectives of
      this study were: to measure and report the vitamin D(3) concentration in serum
      and subcutaneous fat samples from obese individuals and to examine the
      association of vitamin D(3) in fat with vitamin D(3) in serum. This cross
      sectional study was conducted in 17 obese men and women who were scheduled to
      undergo gastric bypass surgery. The mean vitamin D(3) concentration in subjects'
      subcutaneous fat tissue samples was 102.8 +/- 42.0 nmol/kg. The mean vitamin D(3)
      concentration in serum was 7.78 +/- 3.99 nmol/l. Vitamin D(3) concentrations of
      fat tissue and serum were positively correlated (r = 0.68, P = 0.003). Consistent
      with previous findings in obese subjects, subjects in this study had suboptimal
      vitamin D status as demonstrated by a mean 25-hydroxyvitamin D concentration of
      43.3 +/- 15.4 nmol/l. In conclusion, fat tissue vitamin D(3) can be measured by
      LC/MS and is detectable in obese subjects with suboptimal vitamin D status.
      Compatible with the long-standing concept that fat tissue is a storage site for
      vitamin D, fat tissue and serum vitamin D(3) concentrations were positively
      correlated.

PMID- 18338272
TI  - Prevalence of metabolic syndrome and associated risk factors among Turkish
      adults: Trabzon MetS study.
AB  - OBJECTIVE: In order to estimate the prevalence of metabolic syndrome (MetS) as
      defined by NCEP Adult Treatment Panel III (ATP III) criteria in the Trabzon
      Region and its associations with demographic factors (age, sex, marital status,
      reproductive history in women, and level of education), socioeconomic factors
      (household income and occupation), family history of selected medical conditions
      (diabetes, hypertension, and obesity), lifestyle factors (smoking habits,
      physical activity, and alcohol consumption) in the adult population. RESEARCH
      METHODS AND PROCEDURES: In this cross-sectional survey, a sample of households
      was systematically selected from the central province of Trabzon and its nine
      towns. A total of 4,809 adult subjects > or = 20 years (2,601 women and 2,208
      men) were included in the study. Blood pressure levels were measured for all
      subjects. The persons included in the questionnaire were invited to the local
      medical centers for blood examination between 08:00 and 10:00 following 12 h of
      fasting. Fasting serum glucose (FBG) levels and lipid profile were measured with
      autoanalyzer. MetS was defined according to guidelines from the NCEP ATP III
      diagnostic criteria. RESULTS: The prevalence of MetS was 26.9%: 31.3 in women and
      21.7% in men. The prevalence increased with age, being highest in the 60-69-year
      old age group (53.4%) but lower again in the > or = 70 age group. MetS was
      associated positively with marital status, parity, cessation of cigarette
      smoking, and negatively with the level of education, alcohol consumption, current
      cigarette use, household income, and physical activity. Hypertension was found as
      the most common MetS component in our study (57.4%). Others in decreasing order
      were abdominal obesity (40.9%), low high-density lipoprotein-C (HDL-C) (31.8%),
      hypertriglyceridemia (30.7%), and high FBG levels (9.2%). Similarly, in the
      subjects diagnosed with MetS, HT had the highest prevalence (91.9%). This was
      followed by abdominal obesity (82.3%), hypertriglyceridemia (74%), low HDL-C
      (68.6%), and high fasting blood glucose levels (28.6%). DISCUSSION: MetS is
      moderately common and an important health problem in the adult population of
      Trabzon. In order to control MetS and its components, effective public health
      education and taking urgent steps are needed. These steps include serious
      education, providing a well-balanced diet and increasing physical activity.

PMID- 18338273
TI  - [Fibromyalgia syndrome from the perspective of neuropathic pain].
AB  - Fibromyalgia syndrome (FMS) is one of the several chronic pain syndromes and have
      been proposed to reflect some primary abnormality of the nervous system. Patients
      with FMS display common clinical features with neuropathic pain. The responsible
      mechanisms for symptoms and signs are still unknown. Mounting evidence was shown
      for central pain processing abnormalities in almost all FMS patients. These
      anomalies including hyperalgesia, allodynia, abnormal activation of pain-related
      brain regions and abnormal temporal summation of second pain in FMS patients
      strongly indicate a neuropathic pain syndrome. This new information led to the
      proposal that FMS may be a neuropathic pain syndrome maintained by central
      nervous system sensitization and sympathetic hyperactivity. This different
      perspective on FMS opens new avenues for research and treatment. In this review,
      a synthesis of the information about how FMS is related to neuropathic pain
      syndromes is provided.

PMID- 18338274
TI  - [Pain severity and analgesia approaches in adult trauma patients].
AB  - This study was carried out descriptive for determine trauma patient's pain
      severity and pain relief approaches. This scope of the research covered 418
      patients who were between 18-65 years and applied to emergency unit of two
      training hospitals because of the trauma in Istanbul. The data of the research
      were collected by using individual characteristics form and forth section of Mc
      Gill Pain Questionnaire form. It was determined that all patients had pain after
      trauma. Moreover, 14.6 % (n=61) of the patients defined the pain "severe", 51.7 %
      (n=216) that they defined the pain "much severe" and 33.7 %(n=141) that they
      defined the pain "unbearable". Nonsteroid Antiinflammatory Drugs (NSAID) were
      given only 85.9 % (n=359) that they had pain. Besides, being extra to NSAID
      opioid was given to 14.1% (n=59) of the patients by 95.5% (n=416) intramuscular
      approach and 62.9 % (n=293) of the patients, whose pains were not over in spite
      of the pain treatment Based on these results, trauma patients' pains still
      haven't been handled as a serious problem. Also, it can be said that there is hot
      any effective pain relief approach at emergency units yet.

PMID- 18338275
TI  - The preoperative analgesic effect of 3-in-1 block on postoperative pain and
      tramadol consumption in total hip arthroplasty.
AB  - We studied the effect of preoperative 3-in-1 block for total hip replacement
      surgery on postoperative pain and tramadol consumption during patient-controlled
      analgesia. Thirty ASA I-II patients undergoing elective total hip arthroplasty
      (THA) were included in the study. Patients were randomly divided into 2 groups;
      Group I: Patients who received 3-in-1 block with 40 ml of 0.25% bupivacaine 30
      minutes before surgery and later received general anesthesia, Group II: Patients
      who received only a simple needle puncture at the operation site 30-minutes
      before surgery and later received general anesthesia. All patients received
      intravenous tramadol at the end of surgery via a PCA device. Pain was evaluated
      at 0,1/2,1,4,8,12,24 and 48 h at rest and on movement of the hip, using a 10 cm
      VAS. The average intraoperative fentanyl consumption was lower in Group I than in
      Group II. VAS scores were significantly lower in group I, both at rest and during
      movement at all timepoints over in the first postoperative 12 h and also during
      movement 24 h postoperatively. However differences in VAS scores weren't
      clinically significant after 4 hours. In the recovery room, Group I VAS scores
      were only a third of Group II, both at rest and movement (p=0.0001). Total
      tramadol consumption was lower in Group I (633.0+/-119.3 mg) than in Group II
      (991.1+/-41.0 mg). Patient satisfaction scores were higher in Group I than in
      Group II. We concluded that preoperative 3-in-1 block with 40 ml-0,25%
      bupivacaine provides effective postoperative pain relief for elective THA,
      reducing intra-and postoperative analgesic consumption without increase in side
      effects.

PMID- 18338276
TI  - Effect of lornoxicam on postoperative analgesia after myomectomy.
AB  - BACKGROUND: In this prospective, randomized study, we evaluate the postoperative
      analgesic effect of lornoxicam after myomectomy operations. MATERIAL-METHOD:
      Forty ASA I-II patients scheduled for myomectomy operation were enrolled to this
      study. Patients were randomly divided into two groups and epidural block was
      performed with 0,75 % ropivacaine. After the operation, morphine Patient
      Controlled Epidural Analgesia (PCEA) combined with placebo (saline 2 ml iv) and
      morphine PCEA combined with lornoxicam 8 mg iv were administered to patients in
      Group I and Group II, respectively. Pain was assessed at the 0,1st, 2nd, 4th,
      6th, 8th, 12th and 24th hours postoperatively. Chi-square and student's t tests
      were used for statistical analysis. RESULTS: VAS( Visual Analog Scale) scores
      were higher in Group I than Group II at 2nd, 4th, 6th and 24th hours. Total
      morphine consumption was 10.45+/- 4.03 in Group I and 4.25 +/- 1.74 in Group II.
      CONCLUSION: Single dose iv lornoxicam is a safe and an effective treatment option
      of post-myomectomy pain as it produces effective analgesia, reduces morphine
      consumption and does not increase the side effects.

PMID- 18338277
TI  - [Does transcutaneous electrical nerve stimulation or therapeutic ultrasound
      increase the effectiveness of exercise for knee osteoarthritis: a randomized
      controlled study].
AB  - The aim of this study was to determine if transcutaneous electrical nerve
      stimulation (TENS) or therapeutic ultrasound (US) increase the effectiveness of
      exercise on pain, function, muscle strength and quality of life for knee
      osteoarthritis (OA). METHODS: Forty-five patients with primary knee OA diagnosis
      according to American College Rheumatology criteria were sequentially divided
      into 3 random groups. The patients in group 1 received TENS (with superficial
      heat and exercise), group 2 received US (with superficial heat and exercise), and
      group 3 acted as controls (superficial heat and exercise). Outcome measures were
      included as visual analog scale (VAS), a 20-meter walking test, Lequesne index,
      WOMAC scores, isokinetic muscle testing, and the Short Form 36 (SF 36). All
      treatment groups, physical modalities were carried out for a total fifteen
      sessions. All of the patients were subjected to six weeks of exercise program.
      RESULTS: All of the treatment groups had significant improvement on activity VAS,
      20 meter walking test, Lequesne index, WOMAC scores, and most of the sub-scores
      of SF36 when compared with their initial status (p<0.05). All of the treatment
      groups, a significant muscle strength gain in most of the angular velocity in
      knee extensor PT values after the treatment (p<0.05). However there was no
      statistically significant difference after the treatment between the all
      treatment groups (p>0.05). CONCLUSION: All of the treatment groups were effective
      on pain, function, muscle strength and quality of life in patients with knee OA.
      Statistically significant differences could not be found between the treatment
      groups. The exercise program, as it is cheaper, more easily performed and
      efficient, may be preferable for the treatment of knee OA. It is difficult to
      say, TENS or US could increase the effectiveness of isokinetic exercise for pain,
      function, muscle strength and quality of life of knee OA in this study.

PMID- 18338278
TI  - [Efficiency of TENS treatment in hemiplegic shoulder pain: a placebo controlled
      study].
AB  - OBJECTIVE: To evaluate the efficacy of transcutaneous electrical nerve
      stimulation (TENS) therapy on shoulder pain and upper extremity functions in
      hemiplegic patients. MATERIAL-METHODS: Total of 19 hemiplegic patients with
      shoulder pain were as consecutive randomly assigned into two groups. TENS was
      applied in group 1 (n = 10) for 20 minutes and group 2 (n = 9) received placebo
      stimulation. Conventional rehabilitation program were applied total 15 sessions
      during a period of 3 week in both groups.The visual analog scale (VAS) to
      evaluate shoulder pain, Barthel Index (BI) for daily-life activities (DLA) were
      used. The shoulder passive range of motions (PROMs) and Brunnstrom stage of motor
      recovery were measured. RESULTS: Clinical parameters were similar at baseline. In
      both groups, significant improvements were observed in VAS and BI (group 1:
      p<0.001; group 2: p<0.05). In VAS (p<0.001), and BI (p<0.05) were showed
      significant improvements in favor of group 1, when compared with the groups. In
      PROMs of abduction and external rotation of shoulder significant improvements
      were observed in only group 1 (p<0.001, p<0.001 respectively). There was not any
      significant improvement on Brunnstrom stage of motor recovery in both groups
      (p>0.05). CONCLUSION: In conclusion that TENS therapy together with conventional
      rehabilitation could be used as a good alternative therapy in patients with
      hemiplegic shoulder pain.

PMID- 18338279
TI  - Greater occipital nevre block in migraine headache: preliminary results of 10
      patients.
AB  - Despite a favorable clinical experience, there are little evidence existing about
      the effects of greater occipital nerve (GON) block in migraine treatment. In an
      open, preliminary trial we evaluated the use of GON block with 0,5 % bupivacaine,
      in prevention of migraine attacks. Ten women suffering from migraine diagnosed
      according to International Headache Society criteria were evaluated in a six
      month study period. During the treatment and entire follow-up period, the
      patients avoided prophylactic therapy. Patients were given 3 times GON blocks
      with 0.5 % bupivacaine one week intervally. Afterwards blocks were repeated for a
      maximum 5 sessions depending on the clinical response. Clinical evaluation was
      assessed using a monthly Total Pain Index (TPI), and recording of the number of
      migraine attacks and analgesic consumption per month. At the end of the first
      month, TPI reduced from 308.3+/-55.2 to 114,1+/-4.7 (p=0,005). When compared to
      the values before treatment, it was seen that during the first month mean number
      of migraine attacks reduced from 12.6+/-4.8 to 4.9+/-1.8, mean analgesic
      consumption reduced from 11.0+/-3.4 to 4.9+/-1.1, and these reductions lasted up
      to six months. During the treatment no severe advers effect was seen in all
      cases. Although preliminary and obtained on a limited number of patients, our
      results show that the GON block with 1.5 ml of 0.5% bupivacaine does not have any
      severe advers effect and is effective in the prevention of migraine attacks.

PMID- 18338280
TI  - Cutaneous penetration of bisphenol A in pig skin.
AB  - Bisphenol A (BPA) is an endocrine disruptor with weak estrogenic activity, used
      in epoxy resin and polycarbonate plastic. Human exposure may occur by
      contamination from food or food-contact material and by occupational scenarios.
      Occupational health hazards may be associated with allergic contact dermatitis
      (ACD) secondary to BPA exposure. Most ACD occurs in workers handling BPA
      products, such as plastic-product workers, and those exposed to epoxy adhesive
      tapes, foams, and dental products. The present study examined in vitro cutaneous
      penetration of BPA through pig skin, using a Franz cell. After 2, 5, and 10 h of
      exposure, total BPA skin content was 3, 6.9, and 11.4% of the applied dose,
      respectively. BPA remained essentially on the skin surface and penetration mainly
      accumulated in the dermis. As the pig skin model is a reliable predictor of
      percutaneous penetration in humans, these findings may be reassuring for workers
      in contact with BPA-based products.

PMID- 18338281
TI  - Toxicity of carbon tetrachloride to Dunaliella salina, an environmentally
      tolerant alga.
AB  - Carbon tetrachloride (CCl(4)), a water disinfection by-product, at low
      environmentally relevant concentrations exerts adverse effects on mammals. The
      unicellular microalga Dunaliella salina possessing a remarkable degree of
      environmental adaptation was selected as test organism to investigate low-level
      exposure to CCl(4). With incubation with less than 0.13% CCl(4), algae responses
      were similar to control as evidenced by cell growth and levels of beta-carotene,
      a marker of adaptation. The maximal concentration of CCl(4) that D. salina could
      tolerate was 0.2%. Algae incubated with more than 0.32% CCl(4) showed decreased
      growth and reduced beta-carotene levels, which were nondetected after a few days.
      However, after 98 d, D. salina seemed to revive as evidenced by growth and
      returned to the biomass similar to control in another 25 d. Randomly amplified
      polymorphic DNA (RAPD) method was used to compare the genomic DNA difference
      between control and recovered cells. Polymorphic and repeatable RAPD bands
      indicated that chronic effects of CCl(4) to D. salina led generation of altered
      genomic DNA, which may enable the microalga to adapt to survival in an apparently
      toxic substance environment.

PMID- 18338282
TI  - Comparison of the biological activity between ultrafine and fine titanium dioxide
      particles in RAW 264.7 cells associated with oxidative stress.
AB  - Ultrafine or fine titanium dioxide (TiO(2)) particles are widely used in the
      production of white pigments, for sunscreens, and in cleanup techniques. However,
      currently knowledge is deficient concerning cellular responses to these
      particles. The study evaluated and compared the biological activity of ultrafine
      and fine TiO(2) particles in RAW 264.7 macrophages according to an oxidative
      stress paradigm. In vitro exposure of macrophages to ultrafine or fine TiO(2) in
      the range of 0.5-200 microg/ml did not significantly alter cell viability.
      However, ultrafine TiO(2) enhanced intracellular generation of reactive oxygen
      species (ROS) to a greater extent than fine TiO(2) at each exposure
      concentration. Ultrafine TiO(2) induced ERK1/2 activation in a concentration
      dependent manner, while the fine TiO(2)-induced changes were minimal.
      Phosphorylation of ERK1/2 occurred following 10 min exposure to higher
      concentrations of ultrafine TiO(2) (> or = 25 microg/ml). Similarly, ultrafine
      TiO(2) exposure significantly enhanced tumor necrosis factor (TNF)-alpha and
      macrophage inflammatory protein (MIP)-2 secretion in a concentration-dependent
      manner, and its potency was higher than fine TiO(2). These findings suggest that
      when exposure concentration is based upon equivalent mass, ultrafine TiO(2)
      exerts greater biological activity as measured by ROS generation, ERK 1/2
      activation, and proinflammatory mediator secretion in RAW 264.7 macrophages than
      fine TiO(2).

PMID- 18338283
TI  - Interaction of hydration, aging, and carbon content of soil on the evaporation
      and skin bioavailability of munition contaminants.
AB  - Water plays a key role in enhancing the permeability of human skin to many
      substances. To further understand its ability to potentially increase the
      bioavailability of soil contaminants, artificial sweat was applied to excised pig
      skin prior to dosing with munition-contaminated soils. Skin was mounted in
      chambers to allow simultaneous measurement of evaporation and penetration and to
      control air flow, which changed the dwell time of skin surface water within a l-h
      period post application of test materials. Additional variables included type of
      compound, aging of spiked soil samples, and carbon content of soil. To this end,
      the evaporation and skin penetration of C-14 labeled hexahydro-1,3,5-trinitro
      1,3,5-triazine (RDX), 2,6-dinitrotoluene (26DNT), and 2,4,6-trinitrotoluene (TNT)
      were determined from two soil types, Yolo, having 1.2% carbon, and Tinker, having
      9.5% carbon. RDX soil samples aged 27 mo and 62 mo were compared to freshly
      spiked soils samples. Similarly, 26DNT samples aged 35-36 mo and TNT samples aged
      18 mo were compared to freshly spiked samples. Approximately 10 microg/cm(2) of
      radiolabeled compound was applied in 10 mg/cm(2) of soil. Radiolabel recovered
      from the dermis and tissue culture media (receptor fluid) was summed to determine
      percent absorption from the soils. Radiolabel recovered from vapor traps
      determined evaporation. Mean skin absorption of all compounds was higher for low
      carbon soil, regardless of soil age and skin surface water as affected by air
      flow conditions. For 26DNT, a simultaneous increase in evaporation and
      penetration with conditions that favored enhanced soil hydration of freshly
      prepared samples was consistent with a mechanism that involved water displacement
      of 26DNT from its binding sites. A mean penetration of 17.5 +/- 3.6% was observed
      for 26DNT in low-carbon soil, which approached the value previously reported for
      acetone vehicle (24 +/- 6%). 26DNT penetration was reduced to 0.35% under dryer
      conditions and to 0.08% when no sweat was applied. When soil hydration conditions
      were not varied from cell to cell, air flow that favored a longer water dwell
      time increased penetration, but not evaporation, consistent with a mechanism of
      enhanced skin permeability from a higher hydration state of the stratum corneum.
      Profiles of 26DNT penetration versus air flow conditions were exponential for
      freshly prepared soil samples, suggesting strong and weak binding sites;
      corresponding profiles of 26DNT penetration from aged samples were linear,
      suggesting a conversion of weak to strong binding sites. Absorption and
      evaporation was less than 5% for TNT and less than 1% for RDX, regardless of soil
      type and age. Fresh preparations of RDX in Tinker soil and aged samples of TNT in
      Yolo soil showed a significant decrease in skin absorption with loss of surface
      moisture. The penetration rate of radiolabel into the receptor fluid was highest
      during the 1-2 h interval after dosing with 26DNT or TNT. High-performance liquid
      chromatography (HPLC) analysis of 26DNT in receptor fluid at maximum flux
      indicated no metabolism or breakdown. For TNT, however, extensive conversion to
      monoamino derivatives and other metabolites was observed. Relatively little
      radioactivity was found in the dermis after 26DNT and TNT applications, and
      dermal extracts were therefore not analyzed by HPLC. RDX was not sufficiently
      absorbed from soils to allow HPLC analysis. This study has practical
      significance, as the use of water for dust control at remediation sites may have
      the unintended effect of increasing volatilization and subsequent absorption of
      soil contaminants. Soil in contact with sweaty skin may give the same result.
      Skin absorption of 26DNT from soil was over 50-fold higher than the value for
      dryer skin and over 200-fold higher than the value obtained when there was no
      sweat application. While the hydration effect was less dramatic for RDX and TNT,
      soil contaminants more closely matching the physical properties of 26DNT may be
      similarly affected by hydration.

PMID- 18338284
TI  - Immunotoxicity evaluation of jet a jet fuel in female rats after 28-day dermal
      exposure.
AB  - The potential for jet fuel to modulate immune functions has been reported in mice
      following dermal, inhalation, and oral routes of exposure; however, a functional
      evaluation of the immune system in rats following jet fuel exposure has not been
      conducted. In this study potential effects of commercial jet fuel (Jet A) on the
      rat immune system were assessed using a battery of functional assays developed to
      screen potential immunotoxic compounds. Jet A was applied to the unoccluded skin
      of 6- to 7-wk-old female Crl:CD (SD)IGS BR rats at doses of 165, 330, or 495
      mg/kg/d for 28 d. Mineral oil was used as a vehicle to mitigate irritation
      resulting from repeated exposure to jet fuel. Cyclophosphamide and anti-asialo
      GM1 were used as positive controls for immunotoxic effects. In contrast to
      reported immunotoxic effects of jet fuel in mice, dermal exposure of rats to Jet
      A did not result in alterations in spleen or thymus weights, splenic lymphocyte
      subpopulations, immunoglobulin (Ig) M antibody-forming cell response to the T
      dependent antigen, sheep red blood cells (sRBC), spleen cell proliferative
      response to anti-CD3 antibody, or natural killer (NK) cell activity. In each of
      the immunotoxicological assays conducted, the positive control produced the
      expected results, demonstrating the assay was capable of detecting an effect if
      one had occurred. Based on the immunological parameters evaluated under the
      experimental conditions of the study, Jet A did not adversely affect immune
      responses of female rats. It remains to be determined whether the observed
      difference between this study and some other studies reflects a difference in the
      immunological response of rats and mice or is the result of other factors.

PMID- 18338285
TI  - Effects of atrazine on anuran development are altered by the presence of a
      nonlethal predator.
AB  - Although predator-induced stress is a common biotic factor in aquatic communities
      that can strongly influence anuran development, there have been no studies to
      date that examined the interaction between this factor and atrazine, the most
      widely used pesticide in the United States. The potential synergistic effects of
      atrazine (0, 20, or 200 microg/L) and predatory stress on the survival, growth,
      development, and reproductive development of Hyla versicolor (gray treefrog)
      tadpoles were investigated. Atrazine reduced the proportion of tadpoles reaching
      metamorphosis; however, this effect was modified by the presence of a nonlethal
      predator. The combined effects of predatory stress and exposure to 200 microg/L
      atrazine resulted in the lowest proportion of tadpoles reaching metamorphosis. No
      treatment effects were observed for mass, snout-urostyle length, or the
      proportion of metamorphs that were male or female. No macroscopic gonadal
      anomalies were observed. Many gonads were underdeveloped; however, gonadal
      development was more advanced in metamorphs exposed to 200 microg/L atrazine.
      This effect was modified by the presence of a nonlethal predator such that female
      gonadal development was further accelerated and male gonadal development was
      retarded by predatory stress. These results indicate that simplified laboratory
      studies may not accurately reflect the effects of atrazine on anuran development
      in natural communities.

PMID- 18338286
TI  - Particulate matter (PM(2.5), PM(10-2.5), and PM(10)) and children's hospital
      admissions for asthma and respiratory diseases: a bidirectional case-crossover
      study.
AB  - Epidemiological studies reported adverse effects of air pollution on the
      prevalence of respiratory diseases in children. The purpose of this study was to
      examine the association between air pollution and admissions for asthma and other
      respiratory diseases among children who were younger than 15 yr of age. The study
      used data on respiratory hospital admissions and air pollutant concentrations,
      including thoracic particulate matter (PM(10)), fine (PM(2.5)), and coarse (PM(10
      2.5)) particulate matter in Zonguldak, Turkey. A bidirectional case-crossover
      design was used to calculate odds ratios for the admissions adjusted for daily
      meteorological parameters. Significant increases were observed for hospital
      admissions in children for asthma, allergic rhinitis (AR), and upper (UPRD) and
      lower (LWRD) respiratory diseases. All fraction of PM in children showed
      significant positive associations with asthma admissions. The highest association
      noted was 18% rise in asthma admissions correlated with a 10-microg/m(3) increase
      in PM(10-2.5) on the same day of admissions. The adjusted odds ratios for
      exposure to PM(2.5) with an increment of 10 microg/m(3) were 1.15 and 1.21 for
      asthma and allergic rhinitis with asthma, respectively. PM(10) exerted
      significant effects on hospital admissions for all outcomes, including asthma,
      AR, UPRD, and LWRD. Our study suggested a greater effect of fine and coarse PM on
      asthma hospital admissions compared with PM(10) in children.

PMID- 18338287
TI  - Crystalline silica is a negative modifier of pulmonary cytochrome P-4501A1
      induction.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are products of incomplete combustion
      that are commonly inhaled by workers in the dusty trades. Many PAHs are
      metabolized by cytochrome P-4501A1 (CYP1A1), which may facilitate excretion but
      may activate pulmonary carcinogens. PAHs also stimulate their own metabolism by
      inducing CYP1A1. Recent studies suggest that respirable coal dust exposure
      inhibits induction of pulmonary CYP1A1 using the model PAH beta-naphthoflavone.
      The effect of the occupational particulate respirable crystalline silica was
      investigated on PAH-dependent pulmonary CYP1A1 induction. Male Sprague-Dawley
      rats were exposed to intratracheal silica or vehicle and then intraperitoneal
      beta-naphthoflavone, a CYP1A1 inducer, and/or phenobarbital, an inducer of
      hepatic CYP2B1, or vehicle. Beta-naphthoflavone induced pulmonary CYP1A1, but
      silica attenuated this beta-naphthoflavone-induced CYP1A1 activity and also
      suppressed the activity of CYP2B1, the major constitutive CYP in rat lung. The
      magnitude of CYP activity suppression was similar regardless of silica exposure
      dose within a range of 5 to 20 mg/rat. Phenobarbital and beta-naphthoflavone had
      no effect on pulmonary CYP2B1 activity. Both enzymatic immunohistochemistry and
      immunofluorescent staining for CYP1A1 indicated that sites of CYP1A1 induction
      were nonciliated airway epithelial cells, endothelial cells, and the alveolar
      septum. Using immunofluorescent colocalization of CYP1A1 with cytokeratin 8, a
      marker of alveolar type II cells, the proximal alveolar region was the site of
      both increased alveolar type II cells and decreased proportional CYP1A1
      expression in alveolar type II cells. Our findings suggest that in PAH-exposed
      rat lung, silica is a negative modifier of CYP1A1 induction and CYP2B1 activity.

PMID- 18338288
TI  - Is colon cancer mortality related to arsenic exposure?
AB  - Arsenic has been well documented as the major risk factor for blackfoot disease
      (BFD), a unique peripheral vascular disease that was endemic to the southwestern
      coast of Taiwan, where residents consumed high-arsenic artesian well water for
      more than 50 yr. Chronic arsenic exposure was also reported to be associated with
      increased mortality attributed to colon cancer. A tap-water supply system was
      implemented in the early 1960s in the BFD-endemic areas. Artesian well water was
      no longer used for drinking and cooking after the mid-1970s. The objective of
      this study was to determine whether colon cancer mortality decreased after the
      improvement of the drinking-water supply system through elimination of arsenic
      ingestion from artesian well water. Standardized mortality ratios (SMRs) for
      colon cancer were calculated for the BFD-endemic area for the years 1971-2006.
      Results showed that mortality due to colon cancer declined in males, but not in
      females, gradually after the improvement of drinking-water supply system. Based
      on the reversibility criterion, the association between arsenic exposure and
      colon cancer incidence is likely to be causal for males but not females. The
      possibility that our results may be due to chance should be considered; however,
      gender-specific differences in arsenic metabolism may be a critical factor.

PMID- 18338289
TI  - Perceived risk and other predictors and correlates of teenagers' safety belt use
      during the first year of licensure.
AB  - OBJECTIVES: Teenagers have the lowest rate of safety belt use and the highest
      crash rate compared to other age groups. Past studies on teenagers' belt use have
      mostly been cross-sectional. The first goals of this study were to examine, at
      licensure, teenagers' and parents' perceptions of risk of crash/injury for newly
      licensed teenagers when driving unbelted and teenagers' perceived and parents'
      intended consequences for safety belt rule violations. In addition, the
      comparability of these variables to other risky driving behaviors was explored.
      The second goal was to evaluate the importance of these variables in the
      prediction of teenagers' belt use during the first year of licensure, relative to
      other factors related to belt use, including demographics and substance use.
      METHODS: More than 2,000 parent-teenager dyads were interviewed by telephone,
      parents at permit and licensure and teenagers at permit, licensure, and 3, 6, and
      12 months after licensure. RESULTS: Approximately a third of the teenagers
      reported at least once at 3, 6, or 12 months post-licensure not always using
      their safety belt in the past week. At licensure, participants' perceived risk of
      safety belt non-use was high and ranked among the behaviors most related to
      crash/injury for newly licensed teenagers, behind driving under the influence of
      alcohol or drugs. Parent-imposed consequences for safety belt rule violations
      were not as highly rated as parent-imposed consequences for driving under the
      influence of alcohol or drugs. Sequential logistic regression modeled the
      relationship between safety belt use and perceived risk and consequences of non
      use, as well as other prospective predictors assessed at permit and licensure,
      and driving correlates measured after licensure. Teenagers' extreme perceived
      risk and parents' intended sure consequences for non-use were significant
      prospective predictors of regular use during the first year of licensure. Other
      significant predictors and correlates were race (White), high school grade
      average of "A," not smoking cigarettes, driving a passenger vehicle, and never
      receiving a traffic citation or engaging in risky driving behaviors, including
      driving under the influence of alcohol or drugs and running a red light.
      CONCLUSIONS: While the effect size was small for perceived risk of non-use, it is
      a modifiable factor and focused intervention contrived to enhance perceived risk
      could increase teenagers' belt use. Perceived risk is discussed as a target for
      intervention in relation to the Protection Motivation Theory. This theory appears
      helpful in guiding future research into the modifiable factors studied here as
      well as other factors, including perceived rewards and costs associated with non
      use.

PMID- 18338290
TI  - SAM survey on "drugs and fatal accidents": search of substances consumed and
      comparison between drivers involved under the influence of alcohol or cannabis.
AB  - OBJECTIVES: A survey was conducted to produce reliable epidemiological data
      concerning the role played by alcohol and drugs in fatal road accidents in
      France. The aims are to describe the conduct of the survey, evaluate the overall
      quality of the findings, and analyze the substances consumed by the involved
      drivers. A comparison between drivers involved under the influence of alcohol
      only, cannabis only, or both substances is emphasized. METHODS: By a June 1999
      law, all drivers in France involved in an immediate fatality accident between
      October 2001 and 2003 had to undergo a urine test and, if that was not possible
      or the test proved positive, had a blood sample taken in order to test for drugs
      (cannabis, cocaine, heroin, amphetamines). The results were combined with the
      usual procedures of the police force, which include the results of tests for
      illegal alcohol levels. A unique and reliable set of accident data on the role of
      drugs was thus compiled for epidemiological purposes: 10,000 accident reports
      involving over 17,000 drivers were analyzed. The responsibility level of each
      driver involved in an accident was determined. Results were generated for a
      representative sample of about 11,000 drivers. RESULTS: Alcohol levels above the
      legal limit (0.5 g/L of blood) were found in 21% of all drivers involved in
      accidents (killed, injured, or unharmed). Cannabis headed the list of illicit
      drugs detected, with a prevalence of 6.8% (THC > or = 1 ng/mL); it was present in
      the under-35s and especially the under-25s. About 40% of drivers under the
      influence of cannabis also had an illegal alcohol level. The other drugs, whether
      alone or in association with cannabis, are relatively rare. Accident
      characteristics of drivers detected positive for cannabis only are markedly
      different from drivers under the influence of alcohol. The overrepresentation of
      drivers responsible, from 1.7 over the whole population, rises to 2.3 for
      cannabis alone (THC > or = 1 ng/mL), to 9.4 for alcohol alone (> or =0.5 mg/L),
      and to 14.1 for the alcohol-cannabis combination. CONCLUSIONS: The high incidence
      (26%) of alcohol or drugs among the population of drivers involved in fatal
      accidents highlights the importance for road safety of the consumption of these
      substances. Alcohol remains the major risk at any age. Young drivers consuming
      alcohol and cannabis represent a priority target for prevention.

PMID- 18338291
TI  - A new look at NHTSA's evaluation of the 1984 Charlottesville Sobriety Checkpoint
      Program: implications for current checkpoint issues.
AB  - OBJECTIVE: Currently, the implementation of sobriety checkpoint programs, which
      have been demonstrated to be effective in reducing alcohol-related crashes, is
      limited by the belief that they require large consignments of police officers and
      result in few arrests. However, one of the earliest evaluations of a checkpoint
      program in Charlottesville, Virginia, demonstrated that effective checkpoints
      could be mounted in which police officers made as many arrests as officers on
      regular patrols. That study was printed by the NHTSA but was not published in a
      peer-reviewed journal. Because of its significance to current issues in the
      staffing of and procedures for checkpoint operations, this article reanalyzes the
      results of that study and describes the procedures implemented in checkpoints.
      METHODS: A before-and-after control design was used to measure the change in
      nighttime crashes from three baseline years to the program year. Two analyses
      were conducted: the first on the percentage of all crashes occurring at night in
      the test city--Charlottesville--and the second on the percentage of all nighttime
      crashes in the state of Virginia that occurred in the test city. In addition,
      three waves of random-digit-dialing telephone surveys were conducted: one before
      and two during the checkpoint program in the test city, and the comparison city,
      Blacksburg. Finally, the number of impaired-driving arrests per officer hour at
      the checkpoints was compared with the number of arrests per hour by officers on
      regular patrol and the effect on arrests of the use of passive sensors was
      determined. RESULTS: The monthly percentage of nighttime crashes in
      Charlottesville was reduced by 17% (p = 000) in relation to the baseline level.
      The percentage of nighttime crashes in the state of Virginia that occurred in
      Charlottesville was reduced by 11% (p = .013) from baseline levels. Drivers
      arrested at checkpoints had lower BACs than those arrested by the regular
      patrols; however, the conviction rates were the same. The arrest per officer hour
      did not differ significantly between the two types of enforcement operations.
      Awareness of the checkpoint activity was high (72%) among nighttime at-risk
      drivers in the test city. Half reported seeing a checkpoint operation, and a
      quarter reported being interviewed. Use of a passive alcohol sensor by officers
      at the checkpoint increased arrests by almost a factor of three. CONCLUSIONS: The
      results of the evaluation suggest that small-scale sobriety checkpoints can be
      implemented as part of the regular enforcement program in moderate-sized
      jurisdictions and that they can be as efficient in producing arrests as standard
      enforcement patrols, particularly if passive alcohol sensors are used.

PMID- 18338292
TI  - Blood alcohol concentrations in apprehended drivers of cars and boats suspected
      to be impaired by the police.
AB  - OBJECTIVE: According to the Norwegian Road Traffic Act, car drivers are not
      allowed to operate a vehicle with a blood alcohol concentration (BAC) above 0.2
      g/kg. Depending on the size of the boat or ship, boat drivers/captains/first
      mates are not allowed to conduct the boat with a BAC above 0.8 g/kg when driving
      small boats (length less than 15 m) and above 1.5 g/kg when running larger
      vessels/ships. The new Sea Act of June 2005 states that captains/first mates
      cannot conduct a ship if he/she has a BAC above 0.2 g/kg. Our aim was to
      determine the current median BAC in a large population of car and boat drivers in
      Norway. Our other aim was to study if median BAC was higher in boat drivers than
      in car drivers who were suspected by the police to be impaired. Furthermore, we
      wanted to investigate if the BAC levels were differently distributed by gender or
      age within and between these two groups. METHODS: The Norwegian Institute of
      Public Health analyzes blood samples from all car/boat drivers suspected of
      driving under the influence of alcohol and non-alcoholic drugs. In the present
      study, samples submitted between 01.05 and 01.09 in 2002-2004 were included.
      Drivers, who in addition tested positive for drugs or abuse substances other than
      ethanol were excluded. RESULTS: There were 321 boat drivers and 3,061 car drivers
      who were suspected to be under the influence of ethanol only. The median BAC in
      boat drivers (1.76 g/kg [range 0.02-3.54]) was significantly higher compared to
      that in car drivers (1.54 g/kg [range 0.00-4.27]). In the car driver group, the
      mean BAC did not differ significantly between men and women. The median level of
      BAC was significantly higher in men than in women in the boat driver group (1.77
      g/kg with CI 1.69-1.85 vs. 1.27 g/kg with CI 0.78-1.76). CONCLUSIONS: Alcohol
      impairment of car drivers is known to be considered the most important
      contributing cause of car crash injuries. Driving a boat may demand the same
      degree of performance skills as driving a car. The median BAC in apprehended boat
      drivers was considerably high in the present study. The median BAC was also high
      in car drivers despite strict legislation. The population of drivers of cars in
      our study, however, is from previous studies known to contain a large proportion
      of heavy drinkers. Less is known about the drinking habits in boat drivers, and
      caution is needed in generalizing from our results. However, our results indicate
      the possible need for stricter legislation and more frequent police control that
      will hopefully prevent serious accidents caused by ethanol drinking at sea.

PMID- 18338293
TI  - Cellular phone use while driving at night.
AB  - OBJECTIVE: Use of a cellular phone has been shown to negatively affect one's
      attention to the driving task, leading to an increase in crash risk. At any given
      daylight hour, about 6% of US drivers are actively talking on a hand-held cell
      phone. However, previous surveys have focused only on cell phone use during the
      day. Driving at night has been shown to be a riskier activity than driving during
      the day. The purpose of the current study was to assess the rate of hand-held
      cellular phone use while driving at night, using specialized night vision
      equipment. METHODS: In 2006, two statewide direct observation survey waves of
      nighttime cellular phone use were conducted in Indiana utilizing specialized
      night vision equipment. Combined results of driver hand-held cellular phone use
      from both waves are presented in this manuscript. RESULTS: The rates of nighttime
      cell phone use were similar to results found in previous daytime studies. The
      overall rate of nighttime hand-held cellular phone use was 5.8 +/- 0.6%. Cellular
      phone use was highest for females and for younger drivers. In fact, the highest
      rate observed during the study (of 11.9%) was for 16-to 29-year-old females.
      CONCLUSIONS: The high level of cellular phone use found within the young age
      group, coupled with the increased crash risk associated with cellular phone use,
      nighttime driving, and for young drivers in general, suggests that this issue may
      become an important transportation-related concern.

PMID- 18338294
TI  - Japanese high school students' usage of mobile phones while cycling.
AB  - OBJECTIVE: To investigate the perception and actual use of mobile phones among
      Japanese high school students while riding their bicycles, and their experience
      of bicycle crash/near-crash. METHODS: A questionnaire survey was carried out at
      high schools that were, at the time of the survey, commissioned by the National
      Agency for the Advancement of Sports and Health to conduct school safety
      research. RESULTS: In the survey, we found that mobile phone use while riding a
      bicycle was quite common among the students during their commute, but those who
      have a higher perception of danger in this practice, and those who perceived that
      this practice is prohibited, were less likely to engage in this practice. Male
      students and students commuting to school by bicycle only were more likely to
      have used phones while riding. There was a significant relationship between phone
      usage while riding a bicycle and the experience of bicycle crash/near-crash,
      although its causality was not established. Bicycle crash/near-crash experienced
      while using a phone was less prevalent among the students who had a higher
      perception of danger in phone usage while riding, students who perceived that
      this practice is prohibited, and students with a shorter travel time by bicycle
      during the commute. CONCLUSIONS: Since mobile phone use while riding a bicycle
      potentially increases crash risk among cyclists, student bicycle commuters should
      be made aware of this risk. Moreover, they should be informed that cyclists'
      phone usage while riding is prohibited according to the road traffic law.

PMID- 18338295
TI  - Deaths among drivers and right-front passengers in frontal collisions: redesigned
      air bags relative to first-generation air bags.
AB  - OBJECTIVE: After automakers were allowed the option of using sled tests for
      unbelted male dummies to certify the frontal crash performance of vehicles, most
      frontal air bags were depowered, starting in model year 1998, to reduce deaths
      and serious injuries arising from air bag deployments. Concern has been expressed
      that depowering air bags could compromise the protection of adult occupants. This
      study aimed to determine the effects of changes in air bag designs on risk of
      death among front-seat occupants. METHODS: Deaths among drivers and right-front
      passengers per involvement in frontal police-reported crashes during calendar
      years 1998-2004 were compared among vehicles with sled-certified air bags (model
      years 1998-2004) and first-generation air bags (model years 1994-97). Frontal
      crash deaths were identified from the Fatality Analysis Reporting System.
      National estimates of police-reported crashes were derived from the National
      Automotive Sampling System/General Estimates System. Sled certification status
      for model years 1998-2004 was ascertained from published federal data and a
      survey of automobile manufacturers. Passenger cars, pickup trucks, sport utility
      vehicles, and minivans were studied. Stratified analyses were done to compute
      risk ratios (RR) and 95% confidence intervals (95% CI) for driver and right-front
      passenger deaths by air bag generation and crash, vehicle, and driver
      characteristics. RESULTS: In frontal crashes, overall RRs were 0.89 for driver
      deaths (95% CI = 0.74-1.08) and 0.89 for right-front passenger deaths (95% CI =
      0.74-1.07) in sled-certified vehicles compared with first-generation air bag
      equipped vehicles. Child right-front passengers (ages 0-4, 5-9) in vehicles with
      sled-certified air bags had statistically significant reductions in risk of dying
      in frontal collisions, including a 65% reduced risk among ages 0-4 (RR = 0.35;
      95% CI = 0.21-0.60). No differences in effects of sled-certified air bags were
      observed between drivers ages 15-59 and 60-74 in sled-certified vehicles, both of
      whom had RRs slightly below 0.90 (non-significant). Among occupants killed in
      sled-certified vehicles, police-reported belt use was somewhat higher than in
      first-generation vehicles. CONCLUSIONS: No differences in risk of frontal crash
      deaths were observed between adult occupants with sled-certified and first
      generation air bags. Consistent with reports of decreases in air bag-related
      deaths, this study observed significant reductions in frontal deaths among child
      passengers seated in the right-front position in sled-certified vehicles. Higher
      restraint use rates among children in sled-certified vehicles and other vehicle
      design changes might have contributed partially to these reductions.

PMID- 18338296
TI  - Crash injury risks for obese occupants using a matched-pair analysis.
AB  - OBJECTIVE: The automotive safety community is questioning the impact of obesity
      on the performance and assessment of occupant protection systems. This study
      investigates fatality and serious injury risks for front-seat occupants by body
      mass index (BMI) using a matched-pair analysis. It also develops a simple model
      for the change in injury risk with obesity. METHODS: A simple model was developed
      for the change in injury risk with obesity. It included the normal mass (m) and
      stiffness (k) of the body resisting compression during a blunt impact. Stiffness
      is assumed constant as weight is gained (Delta m). For a given impact severity,
      the risk of injury was assumed proportional to compression. Energy balance was
      used to determine injury risks with increasing mass. NASS-CDS field data were
      analyzed for calendar years 1993-2004. Occupant injury was divided into normal
      (18.5 kg/m2 < or = BMI < 25.0 kg/m2) and obese (BMI > o= 30 kg/m2) categories. A
      matched-pair analysis was carried out. Driver and front-right passenger
      fatalities or serious injuries (MAIS 3+) were analyzed in the same crash to
      determine the effect of obesity. This also allowed the determination of the
      relative risk of younger (age < or = 55 years), older (age >55 years), male, and
      female drivers that were obese compared to normal BMI. The family of Hybrid III
      crash test dummies was evaluated for BMI and the amount of ballast was determined
      so they could represent an obese or morbidly obese occupant. RESULTS: Based on
      the simple model, the relative injury risk (r) for an increase in body mass is
      given by: r = (1 + Delta m / m)(0.5). For a given stature, an obese occupant (BMI
      = 30-35 kg/m2) has 54-61% higher risk of injury than a normal BMI occupant (22
      kg/m2). Matched pairs showed that obese drivers have a 97% higher risk of
      fatality and 17% higher risk of serious injury (MAIS 3+) than normal BMI drivers.
      Obese passengers have a 32% higher fatality risk and a 40% higher MAIS 3+ risk
      than normal passengers. Obese female drivers have a 119% higher MAIS 3+ risk than
      normal BMI female drivers and young obese drivers have a 20% higher serious
      injury risk than young normal drivers. This range of increased risk is consistent
      but broader than predicted by the simple injury model. The smallest crash test
      dummies need proportionately more ballast to represent an obese or morbidly obese
      occupant in the evaluation of safety systems. The 5% female Hybrid III has a BMI
      = 20.4 kg/m2 and needs 22 kg of ballast to represent an obese and 44.8 kg to
      represent a morbidly obese female, while the 95% male needs only 1.7 and 36.5 kg,
      respectively. CONCLUSIONS: Obesity influences the risk of serious and fatal
      injury in motor vehicle crashes. The effect is greatest on obese female drivers
      and young drivers. Since some of the risk difference is related to lower seatbelt
      wearing rates, the comfort and use of seatbelt extenders should be examined to
      improve wearing rates. Also, crash testing with ballasted dummies to represent
      obese and morbidly obese occupants may lead to refined safety systems for this
      growing segment of the population.

PMID- 18338297
TI  - Young female drivers in fatal crashes: recent trends, 1995-2004.
AB  - OBJECTIVE: Motor vehicle crashes are the leading cause of death for 15-to 20-year
      olds. In 2004, nearly 8,000 15to 20-year-old drivers were killed in crashes.
      Epidemiologic studies repeatedly identify overrepresentation of young males in
      fatal crashes. Recent studies of young females and risk-taking behaviors (drug
      use, violent crime, risky sexual behavior) show unfavorable trends. The objective
      of this study is to study the extent of contribution of young female drivers to
      national fatal crashes over and to uncover unfavorable trends linked to risky
      driving behavior. METHODS: Data from the National Highway Traffic Safety
      Administration's Fatal Analysis Reporting System (FARS) on drivers in crashes
      with one or more fatalities during 1995-2004 were studied. Five age groups were
      used: 16, 17, 18, 19-20, and 21-24 years. Linear regression was used to measure
      trends over time. The regression results represent differences in proportions and
      changes in proportion of crashes that fell into specified categories. The FARS
      multiple imputation data sets was used to estimate the proportion of drivers with
      positive blood alcohol, and variance estimates were corrected for the imputation
      procedure. RESULTS: In all, 139,000 fatal crashes involving the noted age groups
      occurred over 10 years. Safety restraint use: Females had more safety restraint
      use (by 17.8%) but a smaller increase in use over time. Driver's license
      validity: The percentage of valid licensure decreased over the study for young
      males and females both in the general population and among drivers in fatal
      crashes. Single-vehicle crashes: A lower proportion of female drivers (8.9%
      fewer) were involved in single-vehicle fatal crashes. This proportion changed
      little over the study period. Alcohol use: Females had a 16.7% lower proportion
      than males of alcohol involvement in fatal crashes. This lower proportion was
      seen throughout the age groups. When accounting for change over the study period,
      female drivers had a similar to male increase in alcohol-involved fatal crashes.
      Presence of peer passengers: Female drivers were less likely to have age peers as
      passengers. CONCLUSIONS: While young male drivers surpass young females in number
      of fatal crashes, there are unfavorable trends linked to crash fatalities in
      young females. Our results suggest a smaller increase in safety restraint use,
      proportional decrease in license validity, and an increase in rate of alcohol
      involved fatal crashes that approaches that seen in young males. These findings
      have considerable implications for future traffic safety social marketing
      campaigns, programs, and interventions.

PMID- 18338298
TI  - The combination of two training approaches to improve older adults' driving
      safety.
AB  - OBJECTIVE: An increasing number of older adults rely on the automobile for
      transportation. Educational approaches based on the specific needs of older
      drivers may help to optimize safe driving. We examined if the combination of an
      in-class education program with on-road education would lead to improvements in
      older drivers' knowledge of safe driving practices and on-road driving
      evaluations. METHODS: We used a multisite, randomized controlled trial approach.
      Participants in the intervention group received the in-class and on-road
      education; those in the control group waited and were offered the education
      afterwards. We measured knowledge of safe driving practices before and after the
      in-class component of the program and on-road driving skills before and after the
      whole program. RESULTS: Participants' knowledge improved from 61% of correct
      answers before the in-class education component to 81% after (p < .001). The on
      road evaluation results suggested improvements on some aspects of safe driving
      (e.g., moving in roadway, p < .05) but not on others. CONCLUSIONS: The results of
      this study demonstrate that education programs focused on the needs of older
      drivers may help improve their knowledge of safe driving practices and actual
      driving performance. Further research is required to determine if these changes
      will affect other variables such as driver confidence and crash rates.

PMID- 18338299
TI  - Analysis of seating position and anthropometric parameters of pregnant Japanese
      drivers.
AB  - OBJECTIVE: An anthropometric study was performed to understand the quantitative
      characteristics of the seating posture of Japanese pregnant drivers. METHODS:
      Twenty pregnant women with a mean gestation of 31.4 +/- 1.9 weeks and 20 age
      matched, non-pregnant women provided written informed consent to participate in
      this study. A mid-sized, sedan-type passenger vehicle was used for measurement.
      The subjects, wearing light clothing, sat in the driver's seat of the vehicle and
      fastened the seatbelt after adjusting the seat to their usual driving posture.
      Longitudinal displacement of the slide adjuster and the reclining angle of the
      seat back were measured, relative to the reference position. Seating posture was
      investigated by measuring the coordinates of the anthropometric datum points of
      the drivers (head, shoulder, hip joint, knee joint, and the clearance between the
      steering wheel and the upper torso). RESULTS: The mean horizontal clearance
      between the lower rim of the steering wheel and the abdomen of the pregnant women
      was 146 +/- 56 mm, significantly smaller than that of the non-pregnant women (251
      +/- 51 mm), due to the protrusion of the abdomen. There was no significant
      difference in seat adjustment position between the two groups. The height of the
      pregnant women and the horizontal distance from the lower rim of the steering
      wheel to the abdomen showed a moderate linear correlation in the pregnant group
      (R2 = 0.56). CONCLUSIONS: Compared to previous studies, the differences of
      longitudinal distance were found between American and Japanese subjects without
      significant differences of body heights, due to the difference of body weights
      and abdominal circumferences. This is the first report to analyze the seating
      position and anthropometric parameters of pregnant drivers in an Asian
      population.

PMID- 18338300
TI  - Dynamic pinch tolerance of the phalanges and interphalangeal joints.
AB  - OBJECTIVES: This article presents force and displacement tolerances for pinch
      loading of the bones and joints of the digits. METHODS: Dynamic (54 mm/s) pinch
      loading was applied in a dorsal-palmar direction to all digits (fingers and
      thumb) on matched pairs of hands from 8 adult human cadavers. Opposed 3.1-mm
      thick, 1.0-mm radius of curvature aluminum pinching surfaces were used to
      represent the geometry of moving surfaces in an automobile, such as doors, lift
      gates, or window edges. Injury timing was determined using acoustic sensors. The
      applied force and the distance between the pinching surfaces at the time of an
      acoustic burst were recorded. RESULTS: The force tolerance ranged from 245 N for
      the distal phalanx of the fifth digit (little finger) to 1,155 N for the middle
      phalanx of the second digit (index finger), with a general trend toward
      increasing force tolerance for more proximal anatomical structures. The distance
      between pinching surfaces (gap) at the time of injury ranged from 4.5 mm for the
      distal interphalangeal joint of the fifth digit to 9.1 mm for the proximal
      phalanx of the third digit (middle finger). Orthopedic trauma found during
      necropsy of the test specimens included tuft fractures, transverse fractures,
      cortical crush injuries, a longitudinal fracture, and tendon injuries.
      CONCLUSIONS: A value of approximately 35% of the initial dorsal-palmar dimension
      of the phalanx is reasonably representative of the gap tolerance for all digits
      and loading sites considered here. Although additional testing is required to
      quantify variability in tolerance, the tests here indicate that moving surfaces
      having geometry similar to that considered here would not be expected to injure a
      digit if the opposing surfaces come no closer together than 35% of the digit's
      dorsal-palmar dimension.

PMID- 18338302
TI  - Acetaminophen-induced nephrotoxicity: pathophysiology, clinical manifestations,
      and management.
AB  - Acetaminophen-induced liver necrosis has been studied extensively, but the
      extrahepatic manifestations of acetaminophen toxicity are currently not described
      well in the literature. Renal insufficiency occurs in approximately 1-2% of
      patients with acetaminophen overdose. The pathophysiology of renal toxicity in
      acetaminophen poisoning has been attributed to cytochrome P-450 mixed function
      oxidase isoenzymes present in the kidney, although other mechanisms have been
      elucidated, including the role of prostaglandin synthetase and N-deacetylase
      enzymes. Paradoxically, glutathione is considered an important element in the
      detoxification of acetaminophen and its metabolites; however, its conjugates have
      been implicated in the formation of nephrotoxic compounds. Acetaminophen-induced
      renal failure becomes evident after hepatotoxicity in most cases, but can be
      differentiated from the hepatorenal syndrome, which may complicate fulminant
      hepatic failure. The role of N-acetylcysteine therapy in the setting of
      acetaminophen-induced renal failure is unclear. This review will focus on the
      pathophysiology, clinical features, and management of renal insufficiency in the
      setting of acute acetaminophen toxicity. CASE: A 47-year-old female was found
      lethargic at home and brought by ambulance to an emergency department. History
      from family members suggested an inadvertent acetaminophen overdose, and she had
      last been seen a few hours earlier. She reportedly ingested 18 tablets of 500 mg
      acetaminophen (APAP) over the previous two days because she had run out of her
      prescription pain medication. Her past medical history was significant for
      fibromyalgia, arthritis, and a prior gastric bypass procedure. She had no history
      of alcohol abuse or renal insufficiency. She was lethargic. Vital signs: BP
      128/96 mmHg, pulse 112/min, respirations 32/min; pulse oximetry 98% on 2L nasal
      cannula oxygen. Laboratory studies: BUN 9 mg/dL, creatinine 0.9 mg/dl,
      acetaminophen 12 mcg/mL, AST 5409 u/L and ALT 1085 u/L. A urinalysis was negative
      for blood with trace protein and ketones. A urine drug screen was positive for
      marijuana and opioid metabolites. At the initial hospital, she was treated with N
      acetylcysteine (NAC) orally. Subsequently, she developed fulminant hepatic
      failure with elevated transaminases, hypoglycemia, and coagulopathy (Tables 1A
      and 1B). She was transferred to our facility two days after initial presentation
      for liver transplant evaluation. At that time, her APAP level was 2.0 mg/L. Oral
      NAC therapy was continued after transfer. The patient's liver function
      subsequently improved and she ultimately did not require transplantation. She did
      develop acute renal failure during the course of her hospitalization, with a
      creatinine of 2.3 mg/dL on transfer, which increased to 8.1 mg/dL nine days later
      (approximately 11-13 days post-ingestion). Medical toxicology was consulted by
      the intensive care unit team to address whether this was acetaminophen-induced
      renal failure and if there was a role for NAC in this setting.

PMID- 18338303
TI  - Disease surveillance and nonprescription medication sales can predict increases
      in poison exposure.
AB  - INTRODUCTION: Real-time Outbreak and Disease Surveillance (RODS) is a national
      real-time syndromic surveillance system that classifies hospital registration
      chief complaints into one of seven syndromic categories. The National Retail Data
      Monitor (NRDM) is a public health surveillance tool that is designed to collect
      and analyze the daily sales of 18 categories of nonprescription medications. The
      goal of RODS and NRDM is to provide early warning of disease outbreaks, such as
      biological terrorism. The purpose of this study was to determine whether peak
      syndromic activity and the consequential purchase of nonprescription medications
      could predict an increase in poisoning exposures involving NRDM-monitored
      medications. METHODS: Data from the RODS and NRDM databases were plotted
      graphically to portray activity that occurred during 2003. Data from a regional
      poison information center electronic medical record system that involved all
      human exposure calls related to NRDM monitored medications in 2003 were extracted
      and graphed. Analysis included comparisons between the data sets. RESULTS: Poison
      center exposure volume correlated predictably and simultaneously with the peak
      activity in both the RODS and NRDM databases. DISCUSSION: There was no delay
      between the onset of an influenza outbreak in December 2003, the sale of
      nonprescription palliative mediations, and the increase in poison center exposure
      call volume. Increased availability of and access to nonprescription medications
      resulted in more poisoning exposure calls. CONCLUSIONS: Real-time surveillance
      using other databases can help to forecast poison center activity. This knowledge
      allows the poison center to provide anticipatory guidance to the residents of its
      region.

PMID- 18338304
TI  - A modified goldfrank sniffing bar improves accuracy in identifying simulated
      toxins in a case-based teaching model.
AB  - OBJECTIVE: To determine if olfactory analysis of toxin proxies aid in the
      identification of poisons when compared to case histories alone. METHODS: A
      convenience sample of 42 emergency medicine residents participated in a
      prospective single-blind observational study using a sniffing bar designed with
      the technique described by Goldfrank et.al. Each subject received 12 written
      cases describing a patient with a chemical exposure. Ten chemicals with odors
      corresponding to a specific case history and 2 chemical case controls with no
      odor comprised the sniffing bar. Each subject was asked to identify the toxin
      first by reading the case history alone, then again after smelling the
      corresponding odor. All subjects were asked to record their level of confidence
      for each case before and after the addition of the sniffing bar using a 5-point
      Likert scale. Percentages correct before and after the sniffing bar intervention
      were calculated and two-tailed p-values and 95% confidence intervals were
      measured. Continuous comparative variables such as the means of the Likert scale
      confidence measurements were analyzed with the two-tailed t-test. RESULTS: Median
      percentage of toxins correctly identified was 64.3% (range 9.5-97.6) when based
      on case description alone and 86.9% (range 9.5-95.2) with addition of the
      sniffing bar. The percentage of initially incorrect identification reversed after
      additional data provided by the sniffing bar was 11.5% (range 0-14). Of the 10
      actual toxins, correct identification of 6 achieved statistical significance
      after introduction of the sniffing bar (p=0.0017; 95% CI 4.6-11.4). There was no
      association between level of training and improved accuracy with use of the
      sniffing bar, and overall confidence did not improve significantly after addition
      of the sniffing bar. CONCLUSION: Diagnostic accuracy of poisons in case-based
      scenarios is improved with the use of a sniffing bar. The sniffing bar is a
      useful adjunct to a traditional case-based emergency medicine toxicology teaching
      curriculum.

PMID- 18338305
TI  - Washington Poison Center as perceived by our state's emergency physicians.
AB  - INTRODUCTION: In 1986, we conducted the first survey of Washington emergency
      physicians about their perceptions of the performance of the Washington Poison
      Center (WPC); the results were summarized and published. The exercise was
      repeated in 1993, 1997 and in 2005. METHODS: The original conventional 2-page
      survey was updated and distributed with an explanatory letter and return envelope
      to a mailing list obtained from the state chapter of the American College of
      Emergency Physicians. Responses were tallied, summarized and compared to prior
      surveys. RESULTS: For 2005, 612 surveys were distributed; 221 were returned. The
      average respondent had been in practice for 14 years, with more than 50%
      functioning in "urban" communities. They reported calling the WPC an average of
      19 times per year, and particularly valued being able to consult with a board
      certified medical toxicologist in a virtually "STAT'' manner. In more than 80% of
      calls, the information played a positive role in management of the patient.
      CONCLUSIONS: Washington's emergency physicians continue to highly value the WPC's
      services, with increasing numbers in favor of governmental support of the
      operation.

PMID- 18338306
TI  - A fatal case of venlafaxine overdose.
AB  - INTRODUCTION: Based on its primary action of serotonin reuptake inhibition,
      venlafaxine overdose would be expected to result in serotonergic effects. CASE
      REPORT: A 40 year old male ingested venlafaxine without co-ingestants in a
      suicide attempt. The patient developed refractory ventricular fibrillation and
      expired approximately 9 hours post-ingestion. ECG monitoring revealed significant
      QRS and QTC interval prolongation prior to his demise. DISCUSSION: A literature
      review of venlafaxine overdose cases and investigation into its mechanism of
      action was conducted. The potential for sodium channel blockade and implications
      for therapy are discussed.

PMID- 18338307
TI  - Ingestion of a denture cleanser: did it cause gastric perforation?
AB  - INTRODUCTION: Human ingestion of denture cleansers leading to gastric perforation
      has not previously been described. CASE REPORT: A 27-year-old male ingested three
      denture cleanser tablets in water over two days in an attempt to cause a false
      negative result on a workplace urine drug screen. Seven days later he presented
      to an emergency department with a perforated gastric ulcer. DISCUSSION: A
      literature review of cases and the chemistry of the components of his ingestion
      was conducted to determine the possible relationship between these events.
      Ingestion of intact fragments of the tablets would be likely to result in
      significant gastric toxicity, but ingestion of dissolved tablets would be
      unlikely to have caused his illness.

PMID- 18338308
TI  - A fatal case of iatrogenic hypercalcemia after calcium channel blocker overdose.
AB  - We report a case of a 61-year-old woman treated for a suspected verapamil
      overdose with continuous calcium chloride infusion, resulting in severe
      hypercalcemia of 32.3 mg/dL (8.07 mmol/L) with a normal range of 8.6-10.5 mg/dL
      (2.15-2.63 mmol/L). Treatment with acute hemodialysis rapidly normalized the
      serum calcium level, but the patient later died of vasoconstrictive complications
      of hypercalcemia.

PMID- 18338309
TI  - Serum copper elevation from estrogen effect, masquerading as fungicide toxicity.
AB  - INTRODUCTION: Copper toxicity has previously been reported from the wood
      preservative, copper naphthenate. Serum copper levels may be elevated by
      estrogen. Reported here is a case of a woman who was initially diagnosed with
      elevated serum copper levels from copper naphthenate exposure. She was later
      found to have a normal RBC copper level with resolution of her elevated serum
      copper level following discontinuation of estrogen. CASE REPORT: A previously
      healthy 44-year-old Caucasian female was referred for toxicology consultation due
      to persistently elevated serum copper levels following copper naphthenate applied
      in her home. She had initial nausea, nasal congestion and headache from the fumes
      but then remained asymptomatic. No evidence of underlying systemic disease or
      organ injury was found. Despite this and no further exposure, her serum copper
      remained elevated by 30% above normal over 9 months, peaking at 2301 microg/L (36
      micromol/L). Review of the literature confirmed that oral contraceptive use will
      routinely elevate serum copper levels to the extent noted in this case. Her RBC
      copper level was normal. Cessation of the oral contraceptive for 2 months
      returned the serum copper levels to normal. DISCUSSION: This patient's elevations
      in serum copper were probably unrelated to her chemical exposure to copper
      naphthenate. Serum levels of copper were falsely elevated as a result of
      concomitant estrogen use, and were returned to normal when estrogen was
      discontinued.

PMID- 18338310
TI  - Case files of the medical toxicology fellowship of the California poison control
      system-San Francisco: calcium plus digoxin-more taboo than toxic?
AB  - A 68 year old woman with a history of diabetes mellitus presented to the
      emergency department after experiencing several days of nausea and vomiting.
      Recorded vital signs included: blood pressure 98/32 mm Hg, heart rate 69 bpm,
      "normal" respirations, and no fever. Her initial ECG revealed peaked T waves and
      regular rhythm with no visible P waves. Initial serum electrolytes were notable
      for a potassium level of 7.7 mmol/L, and a creatinine level of 9.6 mg/dL (849
      micromol/L). She was unable to provide a list of her current medications or other
      medical history. There was no old chart immediately available for comparison.

PMID- 18338311
TI  - Medical toxicology and public health--update on research and activities at the
      centers for disease control and prevention and the agency for toxic substances
      and disease registry.

PMID- 18338313
TI  - An imputation strategy for incomplete longitudinal ordinal data.
AB  - A new quasi-imputation strategy for correlated ordinal responses is proposed by
      borrowing ideas from random number generation. The essential idea is collapsing
      ordinal levels to binary ones and converting correlated binary outcomes to
      multivariate normal outcomes in a sensible way so that re-conversion to the
      binary and then ordinal scale, after conducting multiple imputation, yields the
      original marginal distributions and correlations. This conversion process ensures
      that the correlations are transformed reasonably, which in turn allows us to take
      advantage of well-developed imputation techniques for Gaussian outcomes. We use
      the phrase 'quasi' because the original observations are not guaranteed to be
      preserved. We present an application using a data set from psychiatric research.
      We conclude that the proposed method may be a promising tool for handling
      incomplete longitudinal or clustered ordinal outcomes.

PMID- 18338314
TI  - Practical guidelines for assessing power and false discovery rate for a fixed
      sample size in microarray experiments.
AB  - One major goal in microarray studies is to identify genes having different
      expression levels across different classes/conditions. In order to achieve this
      goal, a study needs to have an adequate sample size to ensure the desired power.
      Owing to the importance of this topic, a number of approaches to sample size
      calculation have been developed. However, due to the cost and/or experimental
      difficulties in obtaining sufficient biological materials, it might be difficult
      to attain the required sample size. In this article, we address more practical
      questions for assessing power and false discovery rate (FDR) for a fixed sample
      size. The relationships between power, sample size and FDR are explored. We also
      conduct simulations and a real data study to evaluate the proposed findings.

PMID- 18338315
TI  - Matrix-free laser desorption/ionization of ions landed on plasma-treated metal
      surfaces.
AB  - We report new experiments in which laser desorption/ionization time-of-flight
      mass spectrometry (LDI-TOF-MS) was applied to detection and characterization of
      gramicidin S and IgG pentapeptide (DSDPR) that were reactively landed on plasma
      treated stainless steel surfaces. The distributions of [M+H](+), [M+Na](+) and [M
      + K](+) ion species in LDI-TOF for gramicidin S and IgG pentapeptide (DSDPR) were
      found to be markedly different from those in conventional MALDI-TOF spectra of
      the same samples. LDI-TOF mass spectra showed a strong preference for [M+K](+)
      adducts even in the presence of a large excess of sodium cations, or following
      surface treatment with trifluoroacetic acid. Alkali metal cations (K(+) and
      Cs(+)) can be exchanged in reactively landed peptide samples to provide the
      corresponding cationized peptide ions by LDI. Multiple charged trypsin cations
      were reactively landed into a layer of 2-(4-hydroxyphenylazo)benzoic acid and
      ionized by LDI. The ionization mechanisms for LDI of surface-deposited peptides
      are briefly discussed.

PMID- 18338316
TI  - Effects of high hydrostatic pressure on the growth and beta-carotene production
      of Rhodotorula glutinis.
AB  - The effects of high hydrostatic pressure (HHP) on the biomass and beta-carotene
      biosynthesis of Rhodotorula glutinis R68 were studied. After treatment with five
      repeated cycles at 300 MPa for 15 min, the barotolerant mutant PR68 was obtained.
      After 72 h of culture, the biomass of mutant PR68 was 21.6 g/l, decreased by 8.5%
      compared to the parental strain R68, but its beta-carotene production reached
      19.4 mg/l, increased by 52.8% compared to the parental strain R68. The result of
      restriction fragment length polymorphism (RFLP) analysis suggested that mutant
      strain PR68 was likely to change in nucleic acid level, and thus enhanced beta
      carotene production in this strain as a result of gene mutation induced by HHP
      treatment.

PMID- 18338317
TI  - Expanding the repertoire of plasmids for PCR-mediated epitope tagging in yeast.
AB  - Epitope tagging of yeast proteins provides a convenient means of tracking
      proteins of interest in Western blots and immunoprecipitation experiments without
      the need to raise and test specific antibodies. We have constructed four plasmids
      for use as templates in PCR-based epitope tagging in the yeast Saccharomyces
      cerevisiae. These plasmids expand the range of epitopes available in a tag-URA3
      tag context to include the FLAG, HSV, V5 and VSV-G epitopes. The cloning strategy
      used would be easily applicable to the construction of a similar tag-URA3-tag
      molecule for essentially any desired epitope. Oligonucleotides designed for PCR
      from one plasmid may be used interchangeably with any of the other template
      molecules to allow tagging with different epitopes without the need for new
      primer synthesis. We have tagged Tfc6 with each of the triple epitope tags and
      assessed the efficiency of these epitopes for chromatin immunoprecipitation
      (ChIP). For all the tagged alleles, ChIP occupancy signals are easily detectable
      at known Tfc6 target genes. These new tags provide additional options in
      experimental schemes requiring multiple tagged proteins.

PMID- 18338318
TI  - Dynamic regression hazards models for relative survival.
AB  - A natural way of modelling relative survival through regression analysis is to
      assume an additive form between the expected population hazard and the excess
      hazard due to the presence of an additional cause of mortality. Within this
      context, the existing approaches in the parametric, semiparametric and non
      parametric setting are compared and discussed. We study the additive excess
      hazards models, where the excess hazard is on additive form. This makes it
      possible to assess the importance of time-varying effects for regression models
      in the relative survival framework. We show how recent developments can be used
      to make inferential statements about the non-parametric version of the model.
      This makes it possible to test the key hypothesis that an excess risk effect is
      time varying in contrast to being constant over time. In case some covariate
      effects are constant, we show how the semiparametric additive risk model can be
      considered in the excess risk setting, providing a better and more useful summary
      of the data. Estimators have explicit form and inference based on a resampling
      scheme is presented for both the non-parametric and semiparametric models. We
      also describe a new suggestion for goodness of fit of relative survival models,
      which consists on statistical and graphical tests based on cumulative martingale
      residuals. This is illustrated on the semiparametric model with proportional
      excess hazards. We analyze data from the TRACE study using different approaches
      and show the need for more flexible models in relative survival.

PMID- 18338319
TI  - How conservative is Fisher's exact test? A quantitative evaluation of the two
      sample comparative binomial trial.
AB  - The debate as to which statistical methodology is most appropriate for the
      analysis of the two-sample comparative binomial trial has persisted for decades.
      Practitioners who favor the conditional methods of Fisher, Fisher's exact test
      (FET), claim that only experimental outcomes containing the same amount of
      information should be considered when performing analyses. Hence, the total
      number of successes should be fixed at its observed level in hypothetical
      repetitions of the experiment. Using conditional methods in clinical settings can
      pose interpretation difficulties, since results are derived using conditional
      sample spaces rather than the set of all possible outcomes. Perhaps more
      importantly from a clinical trial design perspective, this test can be too
      conservative, resulting in greater resource requirements and more subjects
      exposed to an experimental treatment. The actual significance level attained by
      FET (the size of the test) has not been reported in the statistical literature.
      Berger (J. R. Statist. Soc. D (The Statistician) 2001; 50:79-85) proposed
      assessing the conservativeness of conditional methods using p-value confidence
      intervals. In this paper we develop a numerical algorithm that calculates the
      size of FET for sample sizes, n, up to 125 per group at the two-sided
      significance level, alpha = 0.05. Additionally, this numerical method is used to
      define new significance levels alpha(*) = alpha+epsilon, where epsilon is a small
      positive number, for each n, such that the size of the test is as close as
      possible to the pre-specified alpha (0.05 for the current work) without exceeding
      it. Lastly, a sample size and power calculation example are presented, which
      demonstrates the statistical advantages of implementing the adjustment to FET
      (using alpha(*) instead of alpha) in the two-sample comparative binomial trial.

PMID- 18338320
TI  - From large analogical instruments to small digital black boxes: 40 years of
      progress in mass spectrometry and its role in proteomics. Part I 1965-1984.
AB  - As the title implies, the author undertakes a personal retrospective on the
      developments that since 1965 have shaped MS and taken it from a position of
      simply playing a role in protein chemistry to becoming an indispensable tool in
      proteomics, all in the past 40-year span. The article reviews the MS timeline of
      events, stopping at various time points where MS made significant contributions
      to protein chemistry or where the development of new instrumentation for MS
      represented a major advance for peptide and protein work. Major highlights in the
      field and their significance for peptide and protein characterization are
      covered, starting from the pioneering work carried out in the 1960s on peptide
      derivative formation and sequencing with instrumentation proper of that time, to
      later work done with triple, quad, and four-sector instruments, and on to the
      more recent work on the characterization of the proteome with ion traps, time-of
      flight (TOF) instruments, and new ionization and tagging techniques.

PMID- 18338321
TI  - Characterization of Ni(II) complexes of Schiff bases of amino acids and (S)-N-(2
      benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide using ion trap and QqTOF
      electrospray ionization tandem mass spectrometry.
AB  - This work demonstrates the application of electrospray ionization mass
      spectrometry (ESI-MS) using two different mass analyzers, ion trap and hybrid
      quadrupole time-of-flight (QqTOF) mass analyzer, for the structural
      characterization of Ni(II) complexes of Schiff bases of (S)-N-(2-benzoylphenyl)-1
      benzylpyrrolidine-2-carboxamide with different amino acids. ESI enables the
      determination of molecular weight on the basis of rather simple positive-ion ESI
      mass spectra containing only protonated molecules and adducts with sodium or
      potassium ions. Fragmentation patterns are characterized by tandem mass
      spectrometric experiments, where both tandem mass analyzers provide complementary
      information. QqTOF data are used for the determination of elemental composition
      of individual ions due to mass accuracies always better than 3 ppm with the
      external calibration, while multistage tandem mass spectra obtained by the ion
      trap are suitable for studying the fragmentation paths. The novel aspect of our
      approach is the combination of mass accuracies and relative abundances of all
      isotopic peaks in isotopic clusters providing more powerful data for the
      structural characterization of organometallic compounds containing polyisotopic
      elements. The benefit of relative and absolute mean mass accuracies is
      demonstrated on the example of studied Ni(II) complexes.

PMID- 18338322
TI  - Conformation-activity relationships of cyclo-constrained micro/delta opioid
      agonists derived from the N-terminal tetrapeptide segment of
      dermorphin/deltorphin.
AB  - The N-terminal tetrapeptide segments of dermorphin (Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser
      NH(2)) and deltorphin (Tyr-D-Ala-Phe-Asp/Glu-Val-Val-Gly-NH(2)) are agonists at
      the opioid receptors micro and delta, respectively. [D-Arg(2), Lys(4)]-dermorphin
      (1-4) amide (Tyr-D-Arg-Phe-Lys-NH(2), DALDA) and [Dmt(1)]DALDA (where Dmt is
      2',6'-dimethyltyrosine) are among the most potent and selective micro-agonists
      reported to date, both in vitro (having picomolar micro receptor affinity) and in
      vivo. In this communication, conformation-activity studies of the following four
      cyclic analogs of DALDA are presented and discussed: the lead peptide S(2),S(4)
      cyclo (Tyr-D-Cys-Phe-Cys-NH(2)), constrained by means of an S(4.2)--S(4.4)
      disulfide between Cys(2) and Cys(4); its two cis and trans C(4.2)--C(4.4)
      olefinic dicarba analogs, and the product of saturation of them both. They are
      potent nonselective or moderately micro-selective opioid agonists in vitro.They
      have been synthesized and tested earlier [Berezowska I, Chung NN, Lemieux C,
      Wilkes BC, and Schiller PW, Acta Biochim Polon 53, 2006, 73-76]. We have studied
      their conformations using NMR and molecular dynamics. With major conformational
      constraints imposed by the 11-membered ring spanning residues 2-4, they show well
      defined conformations of this ring, while the exocylic Tyr(1) and Phe(3) side
      chains still have significant conformational freedom. The more active and
      selective micro versus delta disulfide and saturated dicarba agonists seem to
      have in common: (i) their ring structures more flexible than those of the other
      two and (ii) their ring structures similar to each other and more diverse than
      those in the other two. Given this and the small size of the peptides having
      confirmed bioactivity profiles, there is a chance that their conformations
      determined in solution approach receptor-bound conformations.

PMID- 18338323
TI  - Analysis of the interactions between the peptides from secreted human CKLF1 and
      heparin using capillary zone electrophoresis.
AB  - The Chemokine-like factor 1 (CKLF1) is a novel human cytokine and exhibits
      chemotactic activities on leukocytes. Two peptides named CKLF1-C27 and CKLF1-C19,
      were obtained from secreted CKLF1. In this study, a selective high-performance
      analytical method based on capillary zone electrophoresis (CZE) to investigate
      interactions between heparin and CKLF1-C27/CKLF1-C19 was developed. Samples
      containing CKLF1-C27/CKLF1-C19 and heparin at various ratios were incubated at
      room temperature and then separated by CZE with Tris-acetate buffer at pH 7.2.
      Both qualitative and quantitative characterizations of the binding were
      determined. The binding constants of the interactions between CKLF1-C27/CKLF1-C19
      and heparin were calculated as (3.38 +/- 0.49) x 10(5) M(-1) and (1.10 +/- 0.02)
      x 10(5) M(-1) by Scatchard analysis. To study structural requirements, CKLF1
      C19pm and CKLF1-C19km have been synthesized, and their interactions with heparin
      have been studied by CZE. We found that the Pro or Lys to Ala substitution within
      the residues of CKLF1-C19 (CKLF1-C19pm or CKLF1-C19km) strongly decreased or
      abolished its interaction with heparin, suggesting that the residues of Pro
      affect the affinity of CKLF1-C19 for heparin, and the residues of Lys of CKLF1
      C19 play the important role for the interaction of CKLF1-C19 and heparin,
      respectively. The methodology presented should be generally applicable to study
      peptides and heparin interactions quantitatively and qualitatively.

PMID- 18338324
TI  - Loss of benzene to generate an enolate anion by a site-specific double-hydrogen
      transfer during CID fragmentation of o-alkyl ethers of ortho-hydroxybenzoic
      acids.
AB  - Collision-induced dissociation of anions derived from ortho-alkyloxybenzoic acids
      provides a facile way of producing gaseous enolate anions. The alkyloxyphenyl
      anion produced after an initial loss of CO(2) undergoes elimination of a benzene
      molecule by a double-hydrogen transfer mechanism, unique to the ortho isomer, to
      form an enolate anion. Deuterium labeling studies confirmed that the two hydrogen
      atoms transferred in the benzene loss originate from positions 1 and 2 of the
      alkyl chain. An initial transfer of a hydrogen atom from the C-1 position forms a
      phenyl anion and a carbonyl compound, both of which remain closely associated as
      an ion/neutral complex. The complex breaks either directly to give the phenyl
      anion by eliminating the neutral carbonyl compound, or to form an enolate anion
      by transferring a hydrogen atom from the C-2 position and eliminating a benzene
      molecule in the process. The pronounced primary kinetic isotope effect observed
      when a deuterium atom is transferred from the C-1 position, compared to the weak
      effect seen for the transfer from the C-2 position, indicates that the first
      transfer is the rate determining step. Quantum mechanical calculations showed
      that the neutral loss of benzene is a thermodynamically favorable process. Under
      the conditions used, only the spectra from ortho isomers showed peaks at m/z 77
      for the phenyl anion and m/z 93 for the phenoxyl anion, in addition to that for
      the ortho-specific enolate anion. Under high collision energy, the ortho isomers
      also produce a peak at m/z 137 for an alkene loss. The spectra of meta and para
      compounds show a peak at m/z 92 for the distonic anion produced by the homolysis
      of the O-C bond. Moreover, a small peak at m/z 136 for a distonic anion
      originating from an alkyl radical loss allows the differentiation of para
      compounds from meta isomers.

PMID- 18338325
TI  - Bayesian hierarchical modeling of drug stability data.
AB  - Stability data are commonly analyzed using linear fixed or random effect model.
      The linear fixed effect model does not take into account the batch-to-batch
      variation, whereas the random effect model may suffer from the unreliable shelf
      life estimates due to small sample size. Moreover, both methods do not utilize
      any prior information that might have been available. In this article, we propose
      a Bayesian hierarchical approach to modeling drug stability data. Under this
      hierarchical structure, we first use Bayes factor to test the poolability of
      batches. Given the decision on poolability of batches, we then estimate the shelf
      life that applies to all batches. The approach is illustrated with two example
      data sets and its performance is compared in simulation studies with that of the
      commonly used frequentist methods.

PMID- 18338326
TI  - Survival models for cost data: the forgotten additive approach.
AB  - The usage of the Aalen additive approach is proposed to model cost data. Using a
      Monte Carlo simulation, in a wide set of scenarios, we showed that the Aalen
      model is performing well and can be a reasonable alternative to the standard
      Gamma regression models. In addition, with reference to the COSTAMI trial data,
      we highlighted the ability of the Aalen model to offer additional information
      about the relationships between costs and specific covariates, as compared with
      standard regression techniques.

PMID- 18338327
TI  - CP/MAS spectroscopy in the determination of the tautomeric forms of gossypol, its
      Schiff bases and hydrazones in the solid state.
AB  - New Schiff bases and new hydrazones were synthesized and studied by (13)C and
      (15)N CP/MAS spectroscopy and by (1)H--(1)H COSY, (1)H--(13)C HMBC, (1)H--(13)C
      HSQC, (1)H--(15)N HMQC and (1)H--(15)N HSQC correlations. The CP/MAS
      investigation of gossypol has demonstrated that in the solid state it exists
      exclusively in the aldehyde-aldehyde tautomeric form. In contrast, CP/MAS studies
      of hydrazones and Schiff bases reveal that these compounds occur in the solid
      state in the N-imine-N-imine and enamine-enamine tautomeric forms, respectively.
      It is shown that the (13)C resonances of C-6, C-7 and C-11 carbon atoms are
      suitable for distinguishing between the tautomeric forms of aza-derivatives of
      gossypol in the solid state. Furthermore, we have proved that the (15)N CP/MAS
      spectra can be used to identify these tautomeric forms.

PMID- 18338328
TI  - Real-time measurement of cytosolic free calcium concentration in HL-60 cells
      during static magnetic field exposure and activation by ATP.
AB  - Calcium ions are involved in a number of important signal transduction pathways
      in cells. Cytosolic calcium concentration ([Ca(2+)](c)) can be affected by the
      activation of Ca(2+) channels through the action of ligands such as ATP. The
      response of [Ca(2+)](c) to ligands may be affected by external factors like
      magnetic fields. The purpose of this study was to determine if exposure to a
      static magnetic field (SMF) for 800 s altered the [Ca(2+)](c) response to ATP in
      undifferentiated HL-60 cells. We sham exposed or field exposed fura-2 loaded HL
      60 cells to a SMF of 1, 10, and 100 mT. Cells were activated with ATP 300 s into
      the exposure. The level of [Ca(2+)](c) was followed before, during, and after
      field or sham exposure with a ratiometric fluorescence spectroscopy system. It
      was found that high concentrations of ATP resulted in greater [Ca(2+)](c)
      responses, but faster recovery to near basal levels. The application of 1, 10, or
      100 mT SMF did not affect the [Ca(2+)](c) response to ATP. Future work could
      examine the effect of a longer SMF exposure on the [Ca(2+)](c) response to ATP.
      Longer exposures might provide sufficient time for morphological changes in the
      plasma membrane to occur.

PMID- 18338329
TI  - Syn, anti, and finally both conformations of cyclic AMP are involved in the CRP
      dependent transcription initiation mechanism in E. coli lac operon.
AB  - The cyclic AMP receptor protein (CRP) of Escherichia coli regulates the activity
      of more than 150 genes. Allosteric changes in CRP structure accompanied by cAMP
      binding, initiate transcription through protein binding to specific DNA
      sequences. Initially, researchers proposed a two-site cAMP-binding model for CRP
      dependent transcription activation since biophysical methods showed two
      transitions during titration experiments. Three conformational states were
      considered; apo-CRP, CRP:(cAMP)(1) and CRP:(cAMP)(2), and CRP:(cAMP)(1) was
      proposed as the active form in this initial model. X-ray data indicated an anti
      conformation and in contrast NMR experiments suggested a syn conformation for
      bound cAMPs. For years this paradigm about ligand conformation has been
      ambiguous. When CRP was crystallized with four bound cAMP in the last decade, two
      cAMPs were assigned to syn and the other two to anti conformations. Again three
      conformational states were suggested; apo-CRP, CRP:(cAMP)(2), and CRP:(cAMP)(4).
      This new structure changed the view of CRP allosteric activation from a two-site
      model to a four-site model in the literature and the new model has been supported
      by biochemical and genetic data so far. According to the accepted model, binding
      of the first two cAMP molecules displays positive cooperativity, however, binding
      of the last two cAMP molecules shows negative cooperativity. This resolved the
      conflict between dynamic and static experimental observations. However, this new
      model cannot explain the initiation mechanism as previously proposed because
      functionally active CRP has only one cAMP equivalent. Gene regulation and
      transcription factors are involved in regulating both prokaryotic and eukaryotic
      metabolism. Although gene regulation and expression are much more complex in
      eukaryotes, CRP-mediated transcription initiation is a model of general interest
      to life sciences and medicine. Therefore, the aim of this review is to summarize
      recent works and developments on the cAMP-dependent CRP activation mechanism in
      E. coli.

PMID- 18338330
TI  - POU5F1, encoding a key regulator of stem cell pluripotency, is fused to EWSR1 in
      hidradenoma of the skin and mucoepidermoid carcinoma of the salivary glands.
AB  - The EWSR1 gene is known to play a crucial role in the development of a number of
      different bone and soft tissue tumours, notably Ewing's sarcoma. POU5F1 is
      expressed during early development to maintain the totipotent status of embryonic
      stem and germ cells. In the present study, we report the fusion of EWSR1 and
      POU5F1 in two types of epithelial tumours: hidradenoma of the skin and
      mucoepidermoid carcinoma of the salivary glands. This finding not only broadens
      considerably the spectrum of neoplasms associated with EWSR1 fusion genes but
      also strengthens the evidence for shared pathogenetic mechanisms in the
      development of adnexal and salivary gland tumours. Reminiscent of the previously
      reported fusion genes involving EWSR1, the identified transcript is predicted to
      encode a chimeric protein consisting of the EWSR1 amino-terminal domain and the
      POU5F1 carboxy-terminal domain. We assessed the transcriptional activation
      potential of the chimera compared to the wild-type proteins, as well as
      activation of transcription through the oct/sox composite element known to bind
      POU5F1. Among other POU5F1 target genes, this element is present in the promoter
      of NANOG and in the distal enhancer of POU5F1 itself. Our results show that
      although the chimera is capable of significant transcriptional activation, it may
      in fact convey a negative regulatory effect on target genes.

PMID- 18338331
TI  - Modulation of dendritic spine remodeling in the motor cortex following spinal
      cord injury: effects of environmental enrichment and combinatorial treatment with
      transplants and neurotrophin-3.
AB  - Incomplete spinal cord injury (SCI) elicits structural plasticity of the spared
      motor system, including the motor cortex, which may underlie some of the
      spontaneous recovery of motor function seen after injury. Promoting structural
      plasticity may become an important component of future strategies to improve
      functional outcomes. We have recently observed dynamic changes in the density and
      morphology of dendritic spines in the motor cortex following SCI. The present
      study sought to test whether SCI-induced changes in spine density and morphology
      could be modulated by potential strategies to enhance functional recovery. We
      examined the effects of enriched environment, transplants, and neurotrophin-3 on
      the plasticity of synaptic structures in the motor cortex following SCI. Housing
      rats in an enriched environment increased spine density in the motor cortex
      regardless of injury. SCI led to a more slender and elongated spine morphology.
      Enriched housing mitigated the SCI-induced morphological alterations, suggesting
      that the environmental modification facilitates maturation of synaptic
      structures. Transplantation of embryonic spinal cord tissue and delivery of
      neurotrophin-3 at the injury site further increased spine density when combined
      with enriched housing. This combinatorial treatment completely abolished the
      injury-induced changes, restoring a preinjury pattern of spine morphology. These
      results demonstrated that remodeling of dendritic spines in the motor cortex
      after SCI can be modulated by enriched housing, and the combinatorial treatment
      with embryonic transplants and neurotrophin-3 can potentiate the effects of
      enriched housing. We suggest that synaptic remodeling processes in the motor
      cortex can be targeted for an intervention to enhance functional recovery after
      SCI.

PMID- 18338333
TI  - Ultrasound-guided core-needle biopsy: is it effective in the diagnosis of
      suspected lymphomas presenting in the head and neck?

PMID- 18338334
TI  - The androgen-regulated type II serine protease TMPRSS2 is differentially
      expressed and mislocalized in prostate adenocarcinoma.
AB  - Transmembrane serine protease 2 (TMPRSS2) is an androgen-regulated member of the
      type two transmembrane protease (TTSP) family. Two other members of the TTSP
      family, matriptase and hepsin, are over-expressed in prostate adenocarcinoma and
      mechanistically influence cancer cell invasion and metastasis. This study was
      performed to determine TMPRSS2 protein expression in primary and metastatic
      prostate cancers. We developed a monoclonal antibody capable of the sensitive and
      specific detection of TMPRSS2 protein. TMPRSS2 regulation by androgen and
      presence in seminal fluid was measured. TMPRSS2 localization and expression was
      evaluated in 415 cases of primary prostate cancer and 144 prostate cancer
      metastases by immunohistochemistry. We determined that TMPRSS2 protein expression
      is regulated by androgens and that TMPRSS2 is a component of the normal seminal
      fluid proteome. TMPRSS2 protein is abundantly expressed in the prostate, with low
      levels in the epithelia of the colon, stomach, epididymis and breast. Pancreatic
      acini, hepatic bile ducts, testicular Leydig cells and the kidney also express
      TMPRSS2. In the prostate, TMPRSS2 protein is specifically localized to the
      secretory epithelium, with enhanced expression in the plasma membrane orientated
      towards the ductal lumen. TMPRSS2 expression was significantly higher in both
      neoplastic prostate and in the epithelium of prostatic hyperplasia compared to
      normal epithelium (p < 0.01). TMPRSS2 expression was further elevated in higher
      Gleason grade cancers (patterns 4 and 5) compared to pattern 3 (p = 0.04).
      Furthermore, in most high-grade cancers, TMPRSS2 was mislocalized, being
      expressed in the cytoplasm as well as in the cell membrane. Prostate cancer
      metastases also generally expressed high levels of TMPRSS2. In summary, the
      TMPRSS2 protease is expressed highly in primary and metastatic prostate cancers
      and is associated with tumour cell differentiation. Based on studies with the
      related proteins matriptase and hepsin, TMPRSS2 should be investigated for causal
      roles in prostate carcinogenesis.

PMID- 18338335
TI  - Predictors of discharge destination for 234 patients admitted to a combined
      geriatric medicine/old age psychiatry unit.
AB  - OBJECTIVE: To examine the factors that predicted discharge destinations of all
      patients admitted to a combined geriatric medicine/old age psychiatry unit over a
      4-year period. METHOD: Data regarding discharge destinations, active medical
      problems and demographics of 234 patients admitted to the unit were analysed
      using non-parametric bivariate correlation and logistic regression analysis.
      RESULTS: Independence for activities of daily living (ADL) was the key predictor
      of discharge destination. In combination with the number of active medical
      problems and dementia severity, independence for activities of daily living (ADL)
      defined three distinct groups: patients discharged home, patients discharged to a
      nursing home and patients who died in hospital. CONCLUSIONS: The findings suggest
      that although the key precipitants of admission to joint geriatric medicine/old
      age psychiatric care are behavioural and psychiatric, these factors are
      intercurrent, can be successfully treated in an appropriate environment, and do
      not play a major role in determining discharge outcome. These findings confirm
      the broad spectrum of need among older patients admitted to acute medical care
      identified in previous research and support the case for specialised joint
      provision to address their physical and mental health needs.

PMID- 18338336
TI  - Effects of oral kaempferol on the pharmacokinetics of tamoxifen and one of its
      metabolites, 4-hydroxytamoxifen, after oral administration of tamoxifen to rats.
AB  - It has been reported that tamoxifen is a substrate of P-glycoprotein (P-gp) and
      microsomal cytochrome P450 (CYP) 3A, and kaempferol is an inhibitor of P-gp and
      CYP3A. Hence, it could be expected that kaempferol would affect the
      pharmacokinetics of tamoxifen. Thus, tamoxifen was administered orally (10 mg/kg)
      without or with oral kaempferol (2.5 and 10 mg/kg). In the presence of
      kaempferol, the total area under the plasma concentration-time curve from time
      zero to time infinity (AUC) of tamoxifen was significantly greater, C(max) was
      significantly higher and F was considerably greater than those without
      kaempferol. The enhanced bioavailability of oral tamoxifen by oral kaempferol
      could have been due to an inhibition of CYP3A and P-gp by kaempferol. The
      presence of kaempferol did not alter the pharmacokinetic parameters of a
      metabolite of tamoxifen, 4-hydroxytamoxifen. This could have been because the
      contribution of CYP3A to the formation of 4-hydroxytamoxifen is not considerable
      in rats.

PMID- 18338337
TI  - A devious cube of cancer.

PMID- 18338338
TI  - Dissecting the insecticide-resistance- associated cytochrome P450 gene Cyp6g1.
AB  - BACKGROUND: The cytochrome P450 gene Cyp6g1 is overtranscribed in all field
      isolates of DDT-resistant Drosophila melanogaster (Meigen) and confers a fitness
      advantage when inherited via the female. Overtranscription is associated with the
      insertion of an Accord transposable element into the 5' end of the resistance
      allele. Here the authors attempt to dissect the transcription of the P450 gene in
      order to understand why resistance confers an advantage rather than the expected
      cost. RESULTS: Using a transgenic UAS:GAL4 reporter, the authors document the
      overexpression patterns of green fluorescent protein (GFP) in the fat body,
      midgut and Malpighian tubules driven by flies carrying the resistant 5'
      construct. Knockout of Cyp6g1 via RNAi decreases both the level of Cyp6g1
      transcript and the metabolism of the artificial substrate MROD (methyl ether
      resorufin, Sigma M1544). RNAi does not, however, significantly increase the
      susceptibility of susceptible flies to DDT. Finally, quantification of Cyp6g1 RNA
      in embryos laid by resistant females indicates that they pass on more Cyp6g1 RNA
      to their progeny than their susceptible counterparts. CONCLUSION: These results
      help explain why the eggs and larvae of resistant females enjoy a fitness benefit
      rather than a cost, and suggest that the provisioning of Cyp6g1 RNA to embryos
      provides a direct, but uncharacterised, fitness benefit.

PMID- 18338339
TI  - Fungicide seed treatment efficacy against Microdochium nivale and M. majus in
      vitro and in vivo.
AB  - BACKGROUND: Seed-borne Microdochium majus (Wollenweber) and M. nivale Fries are
      the primary pathogens responsible for Fusarium seedling blight in the UK. The two
      species show differences in pathogenicity, host preference and sensitivities to
      temperature, but their relative sensitivities to fungicide seed treatments are
      unknown. The aim was firstly to determine the efficacy of fungicide seed
      treatments towards single-spore isolates of M. majus and M. nivale using in vitro
      experiments, and subsequently to determine efficacy in vivo over a range of
      temperatures. RESULTS: Differences in EC(50) values between all seed treatments
      were evident from the in vitro experiments and ranged from 0.028 mg L(-1) for
      fludioxonil to 22.8 mg L(-1) for carboxin + thiram. The two seed treatments that
      showed best performance in vitro were used to examine efficacy towards seed-borne
      infection in vivo at 4, 8, 12 and 16 degrees C. Generally, seedling emergence
      improved and the severity of stem-base disease symptoms on emerged seedlings was
      reduced for both species through the use of the fungicides. The combination of
      fludioxonil + difenconazole showed improved performance compared with fludioxonil
      alone. Significantly less severe symptoms were observed through the use of
      fludioxonil and fludioxonil + difenconazole compared with bitertanol +
      fuberidazole at 12 degrees C and for all except one M. nivale infected seed lot
      at 8 degrees C. CONCLUSIONS: Differences in fungicide sensitivity between the two
      species in vitro were not evident in vivo. This is the first report of the effect
      of fungicide seed treatments on the control of seedling blight caused by M. majus
      and M. nivale.

PMID- 18338340
TI  - MIA-QSAR evaluation of a series of sulfonylurea herbicides.
AB  - BACKGROUND: A series of sulfonylurea herbicides has been modelled using a 2D
      image-based QSAR approach known as MIA-QSAR (Multivariate Image Analysis applied
      to QSAR), and highly predictive models have been built. RESULTS: Two MIA-QSAR
      models were built, one group being divided into training and test sets, and the
      other composed of the entire series of compounds. Statistically significant MIA
      QSAR models rendered high correlation coefficients of experimental versus fitted
      pK(i)(app) (AHAS apparent inhibition constant) and satisfactory parameters of
      external validation and leave-one-out cross-validation. Comparison with the
      results obtained from classical 2D QSAR demonstrated some advantages of the
      modelling using MIA descriptors. CONCLUSION: Both MIA-QSAR models showed high
      predictive ability, comparable with that of a reference methodology based on 3D
      descriptors. The method is suggested as a suitable tool for predicting novel
      herbicides.

PMID- 18338341
TI  - Changes in social support and their impact on psychosocial outcome over a 5-year
      period for African American and White dementia caregivers.
AB  - BACKGROUND: African Americans have been found to be more resilient to the
      caregiving role than Whites. Amount of social support and satisfaction with
      social support were studied as possible explanations for these racial
      differences. METHODS: Family caregivers of patients diagnosed as having dementia
      participated in a longitudinal study. There were 166 caregiver-patient dyads
      enrolled and annual follow-up assessments were completed. Linear random effects
      regression models examined the longitudinal trajectories of social support,
      depressive symptoms, and life satisfaction over 5 years of community follow-up.
      Social support was also included as a time-dependent predictor of depressive
      symptoms and life satisfaction. RESULTS: The number of helpful support persons
      available decreased significantly for both racial groups. African American
      caregivers reported more satisfaction with their social support networks than
      Whites. They also reported fewer depressive symptoms and higher levels of life
      satisfaction when compared to their White counterparts. Higher levels of
      satisfaction with social support were associated with fewer depressive symptoms
      and increased levels of life satisfaction and explained a portion of the racial
      differences on these measures of psychosocial outcome. CONCLUSIONS: The
      resilience of African American caregivers, as displayed by their fewer depressive
      symptoms and higher levels of life satisfaction, was partially explained by their
      higher levels of satisfaction with social support. Results suggest that health
      care providers should view low levels of social support as a possible precursor
      to poor psychological outcomes in caregivers. Future research should focus on
      social support and cultural variables that might explain racial differences in
      caregiver outcomes.

PMID- 18338342
TI  - Spectroscopic properties of a strongly anharmonic Mannich base N-oxide.
AB  - Car-Parrinello molecular dynamics simulations in vacuum and in the solid state
      are performed on a strongly anharmonic system, namely, 2-(N-diethylamino-N
      oxymethyl)-4,6-dichlorophenol, to investigate its molecular and spectroscopic
      properties. The investigated compound contains two slightly different molecules
      in the crystal cell with very short intramolecular hydrogen bonds (of 2.400 and
      2.423 A), as determined previously by neutron diffraction. The vibrational
      properties of the compound are studied on the basis of standard approaches, that
      is, Fourier transformation of the autocorrelation functions of the atomic
      velocities and dipole moments. Then, the trajectory obtained from ab initio
      molecular dynamics is sampled and the obtained snapshots are used to solve the
      vibrational Schrodinger equations and to calculate the O--H stretching envelope
      as a superposition of the 0-->1 transition. Using an envelope method, the a
      posteriori quantum effects are included in the O--H stretching. In addition, NMR
      spectra are calculated also using the obtained snapshots. One- and two
      dimensional potentials of mean force (1D and 2D pmf) are derived to explain the
      details of the proton dynamics. The computational results are supported by NMR
      experimental data. In addition, the calculated results are compared with
      previously published X-ray, neutron diffraction, and spectroscopic descriptions.
      A detailed analysis of the bridged proton's dynamics is thus obtained. The
      application of 1D and 2D pmf in a system with a strong bridged-proton
      delocalization is also demonstrated.

PMID- 18338343
TI  - A dynamic model to explain hydration behaviour along the lanthanide series.

PMID- 18338344
TI  - Methyloxy substituted heteroleptic bis(phthalocyaninato) yttrium complexes:
      density functional calculations.
AB  - The effects of alkyloxy substituents attached to one phthalocyanine ligand of
      three heteroleptic bis(phthalocyaninato) yttrium complexes Y(Pc)[Pc(alpha-OCH3)4]
      (1), Y(Pc)[Pc(alpha-OCH3)8] (2), and Y(Pc)[Pc(beta-OCH3)8] (3), as well as their
      reduction products {Y(Pc)[Pc(alpha-OCH3)4]}- (4), {Y(Pc)[Pc(alpha-OCH3)8]}- (5),
      and {Y(Pc)[Pc(beta-OCH3)8]}- (6) [H2Pc(alpha-OCH3)4=1,8,15,22
      tetrakis(methyloxy)phthalocyanine; H2Pc(alpha-OCH3)(8)=1,4,8,11,15,18,22,25
      octakis(methyloxy)phthalocyanine; H2Pc(beta-OCH3)(8)=2,3,9,10,16,17,23,24
      octakis(methyloxy)phthalocyanine] are studied by DFT calculations. Good
      consistency is found between the calculated results and experimental data for the
      electronic absorption, IR, and Raman spectra of 1 and 3. Introduction of electron
      donating methyloxy groups on one phthalocyanine ring of the heteroleptic double
      deckers induces structural deformation in both phthalocyanine ligands, electron
      transfer between the two phthalocyanine rings, changes in orbital energy and
      composition, shift of electronic absorption bands, and different vibrational
      modes of the unsubstituted and substituted phthalocyanine ligands in the IR and
      Raman spectra in comparison with the unsubstituted homoleptic counterpart
      Y(Pc)(2). The calculations reveal that incorporation of methyloxy substituents at
      the nonperipheral positions has greater influence on the structure and
      spectroscopic properties of bis(phthalocyaninato) yttrium double-deckers than at
      the peripheral positions, which increases with increasing number of substituents.
      Nevertheless, the substituent effect of alkyloxy substituents at one
      phthalocyanine ligand of the double-decker on the unsubstituted phthalocyanine
      ring and on the whole molecule and the importance of the position and number of
      alkyloxy substituents are discussed. In addition, the effect of reducing 1-3 to 4
      6 on the structure and spectroscopic properties of the bis(phthalocyaninato)
      yttrium compounds is also discussed. This systemic DFT study is not only useful
      for understanding the structure and spectroscopic properties of
      bis(phthalocyaninato) rare earth metal complexes but also helpful in designing
      and preparing double-deckers with tunable structure and properties.

PMID- 18338345
TI  - Overcoming kinetic limitations of electron injection in the dye solar cell via
      coadsorption and FRET.
AB  - A new, extremely simple concept for the use of energy transfer as a means to the
      enhancement of light absorption and current generation in the dye solar cell
      (DSC) is presented. This model study is based upon a carboxy-functionalized 4
      aminonaphthalimide dye (carboxy-fluorol) as donor, and (NBu4)2[Ru(dcbpy)2(NCS)2]
      (N719) as acceptor chromophores. A set of three different devices is assembled
      containing either exclusively carboxy-fluorol or N719, or a mixture of both. This
      set of transparent devices is characterized via IV-measurements under AM1.5G and
      monochromatic illumination and their light-harvesting and external quantum
      efficiencies (LHE and EQE, respectively) are determined as well. It is shown that
      the device containing only the donor chromophore has a marginal power conversion
      efficiency, thus indicating that carboxy-fluorol is a poor sensitizer for the
      DSC. Cyclovoltametric measurements show that the poor sensitization ability
      arises from the kinetic inhibition of electron injection into the TiO2 conduction
      band. Comparing the spectral properties of the DSCs assembled presently, however,
      demonstrates that light absorbed by carboxy-fluorol is almost quantitatively
      contributing to the photocurrent if N719 is present as an additional sensitizer.
      In this case, N719 acts as a catalyst for the sensitization of TiO2 by carboxy
      fluorol in addition to being a photosensitizer. Evaluation of the maximum output
      power under blue illumination shows that the introduction of an energy-donor
      moiety via coadsorption, leads to a significant increase in the monochromatic
      maximum output power. This result demonstrates that energy transfer between
      coadsorbed chromophores could be useful for the generation of current in dye
      sensitized solar cells.

PMID- 18338346
TI  - Quasi-seeded growth of ligand-tailored PbSe nanocrystals through cation-exchange
      mediated nucleation.

PMID- 18338347
TI  - Allylsilane-vinylarene cross-metathesis enables a powerful approach to
      enantioselective imine allylation.

PMID- 18338348
TI  - Mixed valency in a uranium multimetallic complex.

PMID- 18338349
TI  - A concise approach to vinigrol.

PMID- 18338350
TI  - Polymer-induced transient pores in lipid membranes.

PMID- 18338351
TI  - Specific isotope labeling of colicin E1 and B channel domains for membrane
      topological analysis by oriented solid-state NMR spectroscopy.
AB  - An approach is presented to selectively label the methionines of the colicin E1
      and B channel domains, each about 200 residues in size, and use them for oriented
      solid-state NMR investigations. By combining site-directed mutagenesis, bacterial
      overexpression in a methionine auxotroph E. coli strain and biochemical
      purification, quantitative amounts of the proteins for NMR structural
      investigations were obtained. The proteins were selectively labeled with (15)N at
      only one, or at a few, selected sites. Multidimensional heteronuclear correlation
      high-resolution NMR spectroscopy and mass spectrometry were used to monitor the
      quality of isotopic labeling. Thereafter the proteins were reconstituted into
      oriented phospholipid bilayers and investigated by proton-decoupled (15)N solid
      state NMR spectroscopy. The colicin E1 thermolytic fragment that carries a single
      (15)N methionine within its hydrophobic helix 9 region exhibited (15)N resonances
      that are characteristic of helices that are oriented predominantly parallel to
      the membrane surface at low temperature, and a variety of alignments and
      conformations at room temperature. This suggests that the protein can adopt both
      umbrella and pen-knife conformations.

PMID- 18338352
TI  - Streptomyces phospholipase D mutants with altered substrate specificity capable
      of phosphatidylinositol synthesis.
AB  - The substrate specificity of a phospholipase D (PLD) from Streptomyces
      antibioticus was altered by site-directed saturation mutagenesis, so that it was
      able to synthesize phosphatidylinositol (PI). Mutations were introduced in the
      pld gene at the positions corresponding to three amino acid residues that might
      be involved in substrate recognition, and the mutated genes were expressed in
      Escherichia coli BL21 (DE3). High-throughput screening of approximately 10,000
      colonies for PI-synthesizing activity identified 25 PI-synthesizing mutant PLDs.
      One of these mutant enzymes was chosen for further analysis. The structure of the
      PI synthesized with the mutant enzyme was analyzed by HPLC-MS and NMR. It was
      found that the mutant enzyme generated a mixture of structural isomers of PIs
      with the phosphatidyl groups connected at different positions of the inositol
      ring. The phosphatidylcholine-hydrolyzing activity of the mutant PLD was much
      lower than that of the wild-type enzyme. The mutant enzyme was able to
      transphosphatidylate various cyclohexanols with a preference for bulkier
      compounds. This is the first example of alteration of the substrate specificity
      of PLD and of PI synthesis by Streptomyces PLD.

PMID- 18338353
TI  - BODIPY-based fluorescent redox potential sensors that utilize reversible redox
      properties of flavin.

PMID- 18338354
TI  - Riboswitches for enhancing target gene expression in eukaryotes.

PMID- 18338355
TI  - A sensitive and selective near-infrared fluorescent probe for mercuric ions and
      its biological imaging applications.
AB  - A new mercury(II) near-infrared region fluorescent probe 3,9-dithia-6
      monoazaundecane-tricarbocyanine has been designed and synthesized. It consists of
      two functional moieties: the tricarbocyanine performs as the near-infrared region
      fluorophore, and the 3,9-dithia-6-monoazaundecane acts as the selected binding
      site for metal ions. The near-IR excitation and emission profiles of the probe
      can minimize cell and tissue damage and avoid native fluorescence from natural
      cellular species. It exhibits fluorescence increase upon the binding of the
      Hg(2+) based on the inhibition of the photoinduced electron transfer quenching
      mechanism. Excellent sensitivity and selectivity for mercuric ions are observed
      with this probe. The value of the system is demonstrated by its use in monitoring
      the real-time uptake of Hg(2+) within HepG2 cells and five day old zebrafish. The
      synthesis and remarkable properties of it help to extend the development of metal
      ions fluorescent probes for biological applications.

PMID- 18338356
TI  - 70 S ribosomes bind to Shine-Dalgarno sequences without required dissociations.

PMID- 18338357
TI  - Nanomaterials for rechargeable lithium batteries.
AB  - Energy storage is more important today than at any time in human history. Future
      generations of rechargeable lithium batteries are required to power portable
      electronic devices (cellphones, laptop computers etc.), store electricity from
      renewable sources, and as a vital component in new hybrid electric vehicles. To
      achieve the increase in energy and power density essential to meet the future
      challenges of energy storage, new materials chemistry, and especially new
      nanomaterials chemistry, is essential. We must find ways of synthesizing new
      nanomaterials with new properties or combinations of properties, for use as
      electrodes and electrolytes in lithium batteries. Herein we review some of the
      recent scientific advances in nanomaterials, and especially in nanostructured
      materials, for rechargeable lithium-ion batteries.

PMID- 18338358
TI  - HIV TAT forms pores in membranes by inducing saddle-splay curvature: potential
      role of bidentate hydrogen bonding.

PMID- 18338359
TI  - Synthesis of rhazinicine by a metal-catalyzed C-H bond functionalization
      strategy.

PMID- 18338360
TI  - Thermochemical and physical properties of element 112.

PMID- 18338361
TI  - Cationic Ru(II) complexes with N-heterocyclic carbene ligands for UV-induced ring
      opening metathesis polymerization.

PMID- 18338362
TI  - One building block, two different supramolecular surface-confined patterns:
      concentration in control at the solid-liquid interface.

PMID- 18338363
TI  - Transition-metal complexes with singly reduced 1,2-diketone radical ligands.

PMID- 18338364
TI  - Selective enrichment of trace copper(II) from biological and natural water
      samples by SPE using ion-imprinted polymer.
AB  - A novel Cu(II)-imprinted polymer sorbent was prepared by an ion-imprinted polymer
      (IIP) technique using (2Z)-N,N'-bis(2-aminoethylic)but-2-enediamide as the
      functional monomer and pentaerythritol triacylate as a crosslinker. IR, XPS, and
      elemental analysis techniques were used to confirm the obtained product.
      Subsequently, when this polymer was used as sorbent in SPE, it exhibited
      excellent selectivity for template ion from an aqueous solution. Quantitative
      extraction of Cu(II) was achieved in the pH range of 4-7. The time needed to
      extract each sample was less than 30 min by the batch method. The distribution
      ratio (D) values of IIP for Cu(II) were greatly larger than that for other ions.
      At optimal pH value, the maximum extraction capacity of IIP and nonimprinted
      polymer (NIP) was found to be 29.8 and 7.0 mg/g, respectively. The adsorption
      behavior of Cu(II) on the sorbents could be described by Langmuir adsorption
      isotherm equation. The feasible flow rate of Cu(II)-containing solution for
      quantitative extraction onto the column packed with IIP was 1-4 mL/min, whereas
      for elution it was less than 1 mL/min. The developed method was successfully
      applied to the separation and enrichment of trace Cu(II) in biological and
      natural water samples with satisfactory results.

PMID- 18338365
TI  - HPLC-F analysis of melatonin and resveratrol isomers in wine using an SPE
      procedure.
AB  - An original analytical method has been developed for the determination of the
      antioxidants trans-resveratrol (t-RSV) and cis-resveratrol (c-RSV) and of
      melatonin (MLT) in red and white wine. The method is based on HPLC coupled to
      fluorescence detection. Separation was obtained by using a RP column (C8, 150 mm
      x 4.6 mm id, 5 mum) and a mobile phase composed of 79% aqueous phosphate buffer
      at pH 3.0 and 21% ACN. Fluorescence intensity was monitored at lambda = 386 nm
      while exciting at lambda = 298 nm, mirtazapine was used as the internal standard.
      A careful pretreatment of wine samples was developed, using SPE with C18
      cartridges (100 mg, 1 mL). The calibration curves were linear over the following
      concentration ranges: 0.03-5.00 ng/mL for MLT, 3-500 ng/mL for t-RSV and 1-150
      ng/mL for c-RSV. The LOD values were 0.01 ng/mL for MLT, 1 ng/mL for t-RSV and
      0.3 ng/mL for c-RSV. Precision data, as well as extraction yield and sample
      purification results, were satisfactory. Thus, the method seems to be suitable
      for the analysis of MLT and resveratrol isomers in wine samples. Moreover, wine
      total polyphenol content and antioxidant activity were evaluated.

PMID- 18338366
TI  - New alpha-amino phenylalanine tetrazole ligand for immobilized metal affinity
      chromatography of proteins.
AB  - A new chelating compound has been developed for use in the immobilized metal
      affinity chromatographic (IMAC) separation of proteins. The bidentate ligand,
      alpha-amino phenylalanine tetrazole, 4, was synthesized via a five-step synthesis
      from N-fluorenylmethoxycarbonyl phenylalanine and then immobilized onto silica
      through the epoxide coupling procedure. The binding behavior of the resulting
      IMAC sorbent, following chelation with Zn2+ to a density of 183 micromol Zn2+
      ions/g silica, was characterized by the retention of proteins in the pH range of
      5.0-8.0, and by the adsorption behavior of lysozyme with frontal chromatography
      at pH 6.0 and 8.0. The prepared column showed the separation ability to four test
      proteins and the retention time of these proteins increased with an increase in
      pH. From the derived isotherms, the adsorption capacity, qm, for the binding of
      lysozyme to immobilized Zn2+-alpha-amino phenylalanine tetrazole-silica was found
      to be 1.21 micromol/g at pH 6.0 and 1.20 micromol/g sorbent at pH 8.0,
      respectively, whilst the dissociation constants KD at these pH values were
      5.22x10(-6) and 3.49x10(-6) M, respectively, indicating that the lysozyme was
      retained more stable under alkaline conditions, although the binding capacity in
      terms of micromole protein per gram sorbent remained essentially unchanged.

PMID- 18338367
TI  - Through oven transfer adsorption-desorption interface for the analysis of methyl
      jasmonate in aromatic samples by on-line RPLC-GC.
AB  - A fully automated method for the determination of medium volatility compounds in
      aromatic samples was developed. Specifically, the determination of methyl
      jasmonate in jasmine fragrances was performed by using the through oven transfer
      adsorption-desorption (TOTAD) interface for the on-line coupling between RPLC-GC.
      A study of the most relevant variables involved in the performance of the TOTAD
      interface for medium volatility compounds was carried out by testing different
      values of helium flow (100, 300, 400, and 500 mL/min), transfer speed (0.1, 0.3,
      0.5, and 2.0 mL/min), and methanol/water percentages (86:14, 85:15, 83:17, 80:20,
      and 70:30). The method developed provided satisfactory repeatability (RSD for
      retention times of 0.15% and for peak areas of 9.4%) and recovery (71%) as well
      as excellent LOD (0.01 mg/L) for methyl jasmonate in commercial jasmine essence
      under the experimental conditions selected as optimum. Additional advantages of
      the automated RPLC-TOTAD-GC method proposed in the present work are its
      rapidness, reliability, and the possibility of directly introducing the sample
      with no further pretreatment.

PMID- 18338368
TI  - Iron-catalyzed N-arylations of amides.

PMID- 18338369
TI  - A study of the binding energies of efavirenz to wild-type and K103N/Y181C HIV-1
      reverse transcriptase based on the ONIOM method.
AB  - A three-layered ONIOM model was used to study the interactions between efavirenz
      and the binding sites of HIV-1 reverse transcriptase (RT): wild-type and double
      mutant K103N/Y181C enzyme forms. Binding energies were determined and compared to
      describe the loss of activity of efavirenz with the mutant HIV-1 RT binding
      pocket. The calculated binding energy for the efavirenz-K103N/Y181C HIV-1 RT
      complex is less than that with the wild-type complex by approximately 8 kcal mol(
      1). The interaction energies, calculated at the MP2/6-31G(d,p) level between
      efavirenz and individual residues surrounding the binding pocket of the
      K103N/Y181C enzyme, demonstrate that the attractive interactions between
      efavirenz and residue positions 101 and 103 were less than those for wild-type RT
      by 5.52 and 3.62 kcal mol(-1), respectively. Understanding these interactions
      could be useful in the design of inhibitors specific for the HIV-1 RT allosteric
      site and that have greater potency against the mutant enzyme.

PMID- 18338370
TI  - Effects of a herbal gel containing carvacrol and chalcones on alveolar bone
      resorption in rats on experimental periodontitis.
AB  - Carvacrol and dimeric chalcones are the respective bioactive components of Lippia
      sidoides and Myracrodruon urundeuva, popular medicinal plants of Northeastern
      Brazil with proven antimicrobial and antiinflammatory properties. Periodontal
      disease is associated with inflammation and microbiological proliferation, thus
      the study aimed to investigate the effect of a topical gel based on carvacrol and
      chalcones in the experimental periodontal disease (EPD) in rats. Animals were
      treated with carvacrol and/or chalcones gel, immediately after EPD induction,
      three times a day for 11 days. Appropriate controls were included in the study.
      Animals were weighed daily. They were killed on day 11, the mandibles dissected
      and alveolar bone loss was measured. The periodontium were examined at
      histopathology and the neutrophil influx into the gingiva was assayed using
      myeloperoxidase activity. The bacterial flora were assessed through culture of
      the gingival tissue. Alveolar bone loss was significantly (p < 0.05) inhibited by
      combined carvacrol and chalcones gel, compared with the vehicle and non-treated
      groups. The treatment with the combined gel reduced tissue lesion at
      histopathology, decreased myeloperoxidase activity in gingival tissue and
      inhibited the growth of oral microorganisms as well as the weight loss. Carvacrol
      and chalcones combination gel has a beneficial effect upon EPD in this model.

PMID- 18338371
TI  - Quaternary protein mimetics of gp41 elicit neutralizing antibodies against HIV
      fusion-active intermediate state.
AB  - During viral entry, the fusogenic state of human immunodeficiency virus Type 1
      (HIV-1) envelope protein gp41 is a quaternary structure consisting of three gp41
      glycoproteins, each with two conserved helical domains (N-HR and C-HR). Thus far,
      the examination of monomeric gp41 peptides as an immunologically focused approach
      to vaccine design has not been successful. Here we report an approach using
      quaternary protein mimetics (called 3alpha mimetics) that are based on the gp41 N
      HR and C-HR domains to closely mimic the fusogenic state and overcome the
      deficiencies of the monomeric peptide approach for synthetic vaccine design. The
      3alpha mimetics are conveniently prepared by chemoselective ligation of
      unprotected monomeric peptides to an interstrand linker, and display enhanced
      conformational stability compared to the corresponding monomers. The 3alpha
      mimetics with or without a covalently attached T-helper epitope were immunogenic
      and elicited antisera that bound both recombinant gp160, which contains gp41, and
      HIV-1 virions and immunoprecipitated recombinant gp41. Anti-3alpha mimetic
      antisera neutralized viral infectivity against R5- and X4-tropic strains of HIV-1
      at 31.5 degrees C. The results suggest that a quaternary protein approach to
      mimic conserved and functional domains of viral envelope proteins is desirable
      for HIV vaccine development as such antigens are more likely to produce
      immunologically-focused and broadly neutralizing antibody responses.

PMID- 18338372
TI  - Absolute quantification of cardiac troponin T by means of liquid
      chromatography/triple quadrupole tandem mass spectrometry.
AB  - A liquid chromatography/tandem mass spectrometric method for absolute
      quantification of cardiac troponin T (cTnT) in mouse heart tissue is presented.
      Even in such a complex biological sample, the multiple reaction monitoring
      acquisition mode allowed the selective and sensitive determination of a specific
      peptide, obtained by cTnT enzymatic digestion. The concentration of this cTnT
      specific peptide was considered as a representation of the concentration of its
      parent protein. Quantification was carried out by means of the matrix-matched
      calibration curve, constructed by adding the synthetic standard of the target
      peptide and another synthetic structurally analogous peptide as internal
      standard. Method identification limit and method quantification limit were
      estimated as 60 and 110 ng of cTnT per mg of total extracted proteins,
      respectively. The developed label-free approach has been applied for the absolute
      quantitation of cTnT because of its diagnostic and prognostic value as cardiac
      disease marker. However, the method could be of general application, since it
      requires only the synthesis of two suitable peptides, a protein tryptic cleavage
      product and an internal standard.

PMID- 18338373
TI  - Comparative performance of tripole and quadrupole ion guides at elevated
      pressure.
AB  - This study presents the first practical demonstration of an operational tripole
      ion guide. The transmission was measured for both the tripole and quadrupole ion
      guides at 1 Torr pressure. It was found that the quadrupole provides 2.5-3 times
      better ion transmission efficiency. Two different electric schemes for driving
      the tripole were tested. Similar transmission characteristics were obtained in
      both cases. A brief analysis of the tripole performance and ways to improve it is
      presented.

PMID- 18338374
TI  - Development of a dual-spray electrospray deposition system for matrix-assisted
      laser desorption/ionization time-of-flight mass spectrometry.
AB  - A new method of matrix-assisted laser desorption/ionization (MALDI) sample
      preparation using a dual-spray electrospray deposition system is demonstrated and
      employed for the investigation of gas-phase cationization reactions in the MALDI
      plume. The dual-spray electrospray system is found to increase the homogeneity of
      the sample similarly to that of a conventional single-spray electrospray system.
      The dual-spray electrospray system allows for intimate mixing of separately
      prepared sample components and results in improved quantitative results. The
      development of this device also leads to the possibility of mixing sample
      components prepared in different solvents without the need to be concerned with
      solvent miscibility.

PMID- 18338375
TI  - Negative ion mode matrix-assisted laser desorption/ionisation time-of-flight mass
      spectrometric analysis of oligosaccharides using halide adducts and 9
      aminoacridine matrix.
AB  - 9-Aminoacridine was established as a matrix for the detection of neutral
      oligosaccharides in negative ion mode matrix-assisted laser desorption/ionisation
      time-of-flight (MALDI-TOF) mass spectrometry. Sodium iodide proved to be a useful
      additive inducing formation of stable iodide adducts of the analytes, in
      particular for oligosaccharides with a degree of polymerisation (DP) of three and
      higher. Lower oligomers (DP <3) and monosaccharides show more stable adducts with
      chloride ions. After optimisation of the sample preparation procedure, limits of
      quantitation were determined for alpha-cyclodextrin and cellopentaose at 7 and 13
      pmol, respectively, with a linear detector response over two concentration
      orders. The iodide additive could be successfully employed on MALDI-TOF mass
      spectrometers with vacuum and atmospheric pressure ion sources. The value of the
      new method to solve biological problems has been demonstrated by the analysis of
      a mixture of beta-glucane elicitors isolated from the cell walls of Phytophthora
      sojae.

PMID- 18338376
TI  - The genotoxic effect of potassium metabisulfite using chromosome aberration,
      sister chromatid exchange, micronucleus tests in human lymphocytes and chromosome
      aberration test in bone marrow cells of rats.
AB  - Potassium metabisulfite (PMB) is used as an antimicrobial substance in many kinds
      of foods. In the present study, the effects of PMB on chromosome aberrations
      (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) formation in
      human lymphocytes and as well as its effect on CAs in bone marrow cells of rats
      were investigated. The human lymphocytes were treated with 25, 50, 100, and 200
      microg/ml of PMB for 24 and 48 hr. PMB was also intraperitoneally (ip) injected
      to the rats as a single dose of 150, 300, and 600 mg/kg body weight (b.w.) for 12
      and 24 hr before sacrifice. PMB induced abnormalities such as structural and
      numerical (total) CAs, SCEs, and MN formations in a dose dependent manner in the
      lymphocytes of the 24- and 48-hr treatment periods. In addition, PMB showed a
      cytotoxic effect by decreasing the replication index (RI), mitotic index (MI) and
      nuclear division index (NDI) in a dose dependent manner in human lymphocytes. The
      compound induced CA as well and decreased the MI in bone marrow cells of rats. It
      might be concluded that PMB had a high genotoxic and cytotoxic risk.

PMID- 18338377
TI  - Enhanced sensitivity to DNA damage induced by cooking oil fumes in human OGG1
      deficient cells.
AB  - Cooking oil fumes (COFs) have been implicated as an important nonsmoking risk
      factor of lung cancer in Chinese women. However, the molecular mechanism of COFs
      induced carcinogenicity remains unknown. To understand the molecular basis
      underlying COFs-induced cytotoxicity and genotoxicity as well as the roles of
      hOGG1 in the repair of COFs-induced DNA damage, a human lung cancer cell line
      with hOGG1 deficiency, A549-R was established by using a ribozyme gene targeting
      technique that specifically knockdowned hOGG1 in A549 lung adenocarcinoma cells.
      MTT and comet assays were employed to examine cell viability and DNA
      damage/repair, respectively, in A549-R and A549 cell lines treated with COF
      condensate (COFC). RT-PCR and Western blot results showed that the expression of
      hOGG1 in A549-R cell line was significantly decreased compared with that in A549
      cell line. The concentration of COFC that inhibited cell growth by 50% (the IC50)
      in the A549-R cell line was much lower than that in the A549 cell line, and more
      COFC-induced DNA damage was detected in the A549-R cell line. The time course
      study of DNA repair demonstrated delayed repair kinetics in the A549-R cell line,
      suggesting a decreased cellular damage repair capacity. Our results showed that
      hOGG1 deficiency enhanced cellular sensitivity to DNA damage caused by COFC. The
      results further indicate that hOGG1 plays an important role in repairing COF
      induced DNA damage. Our study suggests that COFs may lead to DNA damage that is
      subjected to hOGG1-mediated repair pathways, and oxidative DNA damage may be
      involved in COF-induced carcinogenesis.

PMID- 18338379
TI  - Osteoprotegerin decreases human osteoclast apoptosis by inhibiting the TRAIL
      pathway.
AB  - Osteoprotegerin (OPG) is a secreted decoy receptor that recognizes RANKL, and
      blocks the interaction between RANK and RANKL, leading to the inhibition of
      osteoclast differentiation and activation. As OPG is a major inhibitor of bone
      resorption, we wondered whether OPG could modulate osteoclast survival/apoptosis.
      Osteoclast apoptosis was evaluated by adding various doses of OPG to human
      osteoclast cultures obtained from cord blood monocytes. Surprisingly, apoptosis
      decreased after adding the OPG. We hypothesized that OPG may block its second
      ligand, TRAIL, which is involved in osteoclast apoptosis. We showed that
      osteoclasts expressed TRAIL, and that TRAIL levels in the culture medium dose
      dependently decreased in presence of OPG, as did the level of activated caspase-8
      in osteoclasts. In addition, the expression of TRAIL by osteoclasts was not
      affected in the presence of OPG. Our findings suggest that OPG inhibits
      osteoclast apoptosis, at least in part, by binding and thus inhibiting
      endogenously produced TRAIL in human osteoclast cultures. TRAIL could be an
      autocrine factor for the regulation of osteoclast survival/apoptosis.

PMID- 18338380
TI  - Evidence for communality in the primary determinants of CYP74 catalysis and of
      structural similarities between CYP74 and classical mammalian P450 enzymes.
AB  - In silico structural analysis of CYP74C3, a membrane-associated P450 enzyme from
      the plant Medicago truncatula (barrel medic) with hydroperoxide lyase (HPL)
      specificity, showed that it had strong similarities to the structural folds of
      the classical microsomal P450 enzyme from rabbits (CYP2C5). It was not only the
      secondary structure predictions that supported the analysis but site directed
      mutagenesis of the substrate interacting residues was also consistent with it.
      This led us to develop a substrate-binding model of CYP74C3 which predicted three
      amino acid residues, N285, F287, and G288 located in the putative I-helix and
      distal haem pocket of CYP74C3 to be in close proximity to the preferred substrate
      13-HPOTE. These residues were judged to be in equivalent positions to those
      identified in SRS-4 of CYP2C5. Significance of the residues and their relevance
      to the model were further assessed by site directed mutagenesis of the three
      residues followed by EPR spectroscopic and detailed kinetic investigations of the
      mutated proteins in the presence and absence of detergent. Although point
      mutation of the residues had no effect on the haem content of the mutated
      proteins, significant effects on the spin state equilibrium of the haem iron were
      noted. Kinetic effects of the mutations, which were investigated using three
      different substrates, were dramatic in nature. In the presence of detergent with
      the preferred substrate (13-HPOTE), the catalytic center activities and substrate
      binding affinities of the mutant proteins were reduced by a factor of 8-32 and 4
      12, respectively, compared with wild-type--a two orders of magnitude reduction in
      catalytic efficiencies. We believe this is the first report where primary
      determinants of catalysis for any CYP74 enzyme, which are fully consistent with
      our model, have been identified. Our working model predicts that N285 is close
      enough to suggest that a hydrogen bond with the peroxy group of the enzyme
      substrate 13-HPOTE is warranted, whereas significance of F287 may arise from a
      strong hydrophobic interaction between the alkyl group(s) of the substrate and
      the phenyl ring of F287. We believe that G288 is crucial because of its size. Any
      other residue with a relatively bulky side chain will hinder the access of
      substrate to the active site. The effects of the mutations suggests that subtle
      protein conformational changes in the putative substrate-binding pocket regulate
      the formation of a fully active monomer-micelle complex with low-spin haem iron
      and that structural communication exists between the substrate- and micelle
      binding sites of CYP74C3. Conservation in CYP74 sequence alignments suggests that
      N285, F287, and G288 in CYP74C3 and the equivalent residues at positions in other
      CYP74 enzymes are likely to be critical to catalysis. To support this we show
      that G324 in CYP74D4 (Arabidopsis AOS), equivalent to G288 in CYP74C3, is a
      primary determinant of positional specificity. We suggest that the overall
      structure of CYP74 enzymes is likely to be very similar to those described for
      classical P450 monooxygenase enzymes.

PMID- 18338378
TI  - The role of viral and bacterial pathogens in gastrointestinal cancer.
AB  - The association of Helicobacter pylori (H. pylori) with gastric cancer is thus
      far the best understood model to comprehend the causal relationship between a
      microbial pathogen and cancer in the human gastrointestinal tract. Besides H.
      pylori, a variety of other pathogens are now being recognized as potential
      carcinogens in different settings of human cancer. In this context, viral causes
      of human cancers are central to the issue since these account for 10-20% of
      cancers worldwide. In the case of H. pylori and gastric cancer, as well as the
      human papillomavirus and anal cancer, the causal relationship between the
      infectious agent and the related cancer in the gastrointestinal tract has been
      clearly confirmed by epidemiological and experimental studies. Similarly, Epstein
      Barr virus and the oncogenic JC virus are being suggested as possible causative
      agents for cancers in the upper and lower gastrointestinal tract. This review
      discusses various viral and microbial pathogens and their oncogenic properties in
      the evolution of gastrointestinal carcinogenesis and summarizes the available
      experimental data make a convincing agreement favoring the associations between
      infectious agents and specific human cancers.

PMID- 18338381
TI  - Crystal structure of uncharacterized protein TTHA1756 from Thermus thermophilus
      HB8: Structural variety in UPF0150 family proteins.

PMID- 18338382
TI  - Structural and enzymatic characterization of HP0496, a YbgC thioesterase from
      Helicobacter pylori.
AB  - YbgC proteins are bacterial acyl-CoA thioesterases associated with the Tol-Pal
      system. This system is important for cell envelope integrity and is part of the
      cell division machinery. In E. coli, YbgC associates with the cell membrane and
      is part of a protein network involved in lipid biogenesis. In the human pathogen
      Helicobacter pylori, a putative homologue of YbgC, named HP0496, was found to
      interact with the cytotoxin CagA by two different studies. We have determined its
      crystal structure and characterized its enzymatic activity. The structure of
      HP0496 shows that it is a member of the hot-dog family of proteins, with a
      epsilongamma tetrameric arrangement. Finally, enzymatic assays performed with the
      purified protein showed that HP0496 is an acyl-CoA thioesterase that favors long
      chain substrates.

PMID- 18338383
TI  - Crystal structure of single-domain VL of an anti-DNA binding antibody 3D8 scFv
      and its active site revealed by complex structures of a small molecule and
      metals.

PMID- 18338384
TI  - Refining homology models by combining replica-exchange molecular dynamics and
      statistical potentials.
AB  - A protocol is presented for the global refinement of homology models of proteins.
      It combines the advantages of temperature-based replica-exchange molecular
      dynamics (REMD) for conformational sampling and the use of statistical potentials
      for model selection. The protocol was tested using 21 models. Of these 14 were
      models of 10 small proteins for which high-resolution crystal structures were
      available, the remainder were targets of the recent CASPR exercise. It was found
      that REMD in combination with currently available force fields could sample near
      native conformational states starting from high-quality homology models.
      Conformations in which the backbone RMSD of secondary structure elements (SSE
      RMSD) was lower than the starting value by 0.5-1.0 A were found for 15 out of the
      21 cases (average 0.82 A). Furthermore, when a simple scoring function consisting
      of two statistical potentials was used to rank the structures, one or more
      structures with SSE-RMSD of at least 0.2 A lower than the starting value was
      found among the five best ranked structures in 11 out of the 21 cases. The
      average improvement in SSE-RMSD for the best models was 0.42 A. However, none of
      the scoring functions tested identified the structures with the lowest SSE-RMSD
      as the best models although all identified the native conformation as the one
      with lowest energy. This suggests that while the proposed protocol proved
      effective for the refinement of high-quality models of small proteins scoring
      functions remain one of the major limiting factors in structure refinement. This
      and other aspects by which the methodology could be further improved are
      discussed.

PMID- 18338386
TI  - Effects of ligand binding on the dynamics of rice nonspecific lipid transfer
      protein 1: a model from molecular simulations.
AB  - Plant nonspecific lipid transfer proteins (nsLTPs) are small, basic proteins
      constituted mainly of alpha-helices and stabilized by four conserved disulfide
      bridges. They are characterized by the presence of a tunnel-like hydrophobic
      cavity, capable of transferring various lipid molecules between lipid bilayers in
      vitro. In this study, molecular dynamics (MD) simulations were performed at room
      temperature to investigate the effects of lipid binding on the dynamic properties
      of rice nsLTP1. Rice nsLTP1, either in the free form or complexed with one or two
      lipids was subjected to MD simulations. The C-terminal loop was very flexible
      both before and after lipid binding, as revealed by calculating the root-mean
      square fluctuation. After lipid binding, the flexibility of some residues that
      were not in direct contact with lipid molecules increased significantly,
      indicating an increase of entropy in the region distal from the binding site.
      Essential dynamics analysis revealed clear differences in motion between
      unliganded and liganded rice nsLTP1s. In the free form of rice nsLTP1, loop1
      exhibited the largest directional motion. This specific essential motion mode
      diminished after binding one or two lipid molecules. To verify the origin of the
      essential motion observed in the free form of rice nsLTP1, we performed multiple
      sequence alignments to probe the intrinsic motion encoded in the primary
      sequence. We found that the amino acid sequence of loop1 is highly conserved
      among plant nsLTP1s, thus revealing its functional importance during evolution.
      Furthermore, the sequence of loop1 is composed mainly of amino acids with short
      side chains. In this study, we show that MD simulations, together with essential
      dynamics analysis, can be used to determine structural and dynamic differences of
      rice nsLTP1 upon lipid binding.

PMID- 18338387
TI  - A mathematically related singularity and the maximum size of protein domains.
AB  - In a paper titled "A topologically related singularity suggests a maximum
      preferred size for protein domains" (Zbilut et al., Proteins 2007;66:621-629),
      Zbilut et al. claim to have found a singularity in certain geometrical properties
      of protein structures, and suggest that this singularity may limit the maximum
      size of protein domains. They find further support for the singularity in their
      analysis of G-factors calculated by the PROCHECK program. Here, we show that the
      claimed singularity is a mathematical artifact with no physical meaning, and we
      reanalyze the G-factors to show that Zbilut et al.'s results are due to a single
      outlier in the data. Thus, the existence of an actual singularity in the
      topological properties of proteins is not supported by the findings of Zbilut et
      al.

PMID- 18338388
TI  - 3-substituted BINOL Schiff bases and their reductive products for catalytic
      asymmetric addition of diethylzinc to aldehydes.
AB  - Three new chiral 3-substituted BINOL Schiff bases and their reductive 3
      arylaminomethyl BINOL products have been synthesized and used for the asymmetric
      addition reaction of diethylzinc to aldehydes in the presence of titanium
      tetraisopropoxide. The reaction provided optically active secondary alcohols in
      high yield (86-100%) and good enantioselectivity (up to 92% ee).

PMID- 18338389
TI  - Fetal ethanol exposure activates protein kinase A and impairs Shh expression in
      prechordal mesendoderm cells in the pathogenesis of holoprosencephaly.
AB  - BACKGROUND: In humans, fetal ethanol exposure can cause holoprosencephaly (HPE),
      one of the most common birth defects that is characterized by brain, facial, and
      oral abnormalities. However, the pathogenesis of HPE is not clear. In the present
      study, we investigated the teratogenic mechanism of ethanol-induced brain and
      facial malformations in mice. METHODS: Pregnant C57BL/6J mice were administered
      ethanol on E7 and facial and brain malformations were characterized on E10.5. We
      examined the effect of fetal ethanol exposure on Shh expression and activation of
      protein kinase A (PKA) because mutations in the human Shh gene are the most
      frequent cause of autosomal-dominant inherited HPE and PKA is a potent endogenous
      antagonist of Shh signaling. RESULTS: Fetal ethanol exposure on E7 induced severe
      midline defects characteristic of HPE. Ethanol exposure impaired Shh expression
      and induced excessive apoptosis only along the anterior edge of the prechordal
      mesendoderm (PME). In addition, ethanol activated PKA in anterior PME cells.
      Pretreatment of embryos with antioxidants, such as vitamins C or E, prevented the
      development of ethanol-induced HPE. CONCLUSIONS: Shh expression in PME cells is
      involved in the pathogenesis of ethanol-induced HPE. Ethanol may impair Shh
      expression indirectly by activating PKA. The inhibition of excessive apoptosis in
      PME cells by antioxidants implies that oxidative stress may underlie the
      teratogenic actions of ethanol. Thus, antioxidant treatment may be a simple
      preventative measure that could reduce the incidence of HPE following fetal
      ethanol exposure.

PMID- 18338390
TI  - Seven-week embryo with gastroschisis, multiple anomalies, and physiologic hernia
      suggests early onset of gastroschisis.
AB  - Gastroschisis is an increasingly common birth defect involving the development of
      the ventral body wall. Extrusion of the bowel is usually paraumbilical, usually
      right sided, and associated anomalies are less common than in omphalocele.
      Recently, hypotheses regarding the timing of the typical gastroschisis defect
      have come into question. Unlike previous theories, Feldkamp et al. (2007) has
      postulated that gastroschisis occurs much earlier in development, before
      abdominal wall closure, which is completed by about 35 days postconception. We
      present a case of a spontaneously aborted dysmorphic embryo which exhibits
      features of the normal physiologic herniation of the midgut as well as
      gastrochisis. The co-existence of the abdominal wall defect in this abnormal
      embryo with the physiologic hernia supports the early development of this defect
      and also illustrates the causal heterogeneity of gastroschisis.

PMID- 18338391
TI  - Decline in the prevalence of neural tube defects following folic acid
      fortification and its cost-benefit in South Africa.
AB  - BACKGROUND: In October 2003 South Africa embarked on a program of folic acid
      fortification of staple foods. We measured the change in prevalence of NTDs
      before and after fortification and assessed the cost benefit of this primary
      health care intervention. METHODS: Since the beginning of 2002 an ecological
      study was conducted among 12 public hospitals in four provinces of South Africa.
      NTDs as well as other birth defect rates were reported before and after
      fortification. Mortality data were also collected from two independent sources.
      RESULTS: This study shows a significant decline in the prevalence of NTDs
      following folic acid fortification in South Africa. A decline of 30.5% was
      observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49-0.98; p =
      .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed
      a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally,
      oro-facial clefts showed no significant decline (5.7%). An independent perinatal
      mortality surveillance system also shows a significant decline (65.9%) in NTD
      perinatal deaths, and in NTD infant mortality (38.8%). CONCLUSIONS: The decrease
      in NTD rates postfortification is consistent with decreases observed in other
      countries that have fortified their food supplies. This is the first time this
      has been observed in a predominantly African population. The economic benefit
      flowing from the prevention of NTDs greatly exceeds the costs of implementing
      folic acid fortification.

PMID- 18338392
TI  - Mortality rates in subjects with fetal alcohol spectrum disorders and their
      siblings.
AB  - BACKGROUND: Our objective was to estimate the mortality rate in subjects with
      fetal alcohol spectrum disorders (FASD) and their siblings whose FASD status was
      unknown. METHODS: We used the state FASD Registry to link subjects with FASD to a
      North Dakota birth certificate. We were able to link 304 of 486 cases (63%). We
      used the birth certificates to identify the mother and children born to the
      mother (siblings). We then searched for death certificates for both the FASD
      cases and their siblings. We then calculated the annual and age-adjusted
      mortality rates for the siblings of the Registry cases and compared them with
      mortality rates from North Dakota. RESULTS: The FASD case mortality rate was
      2.4%, with a 4.5% mortality rate for their sibings, accounting for 14% of all
      deaths when compared to the North Dakota residents matched by age and year of
      death. The sibling deaths accounted for 21.5% of all cause mortality matched by
      age and year of death. The age-standardized mortality ratios were 4.9 for the
      FASD cases and 2.6 for their siblings whose FASD status was unknown. CONCLUSIONS:
      Mortality rates for FASD cases and their siblings were increased and represent a
      substantial proportion of all cause mortality in North Dakota. Prevention of FASD
      may be a useful strategy to decrease mortality.

PMID- 18338393
TI  - Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase
      gene (GBA).
AB  - Gaucher disease (GD) is an autosomal recessive disorder caused by the deficiency
      of glucocerebrosidase, a lysosomal enzyme that catalyses the hydrolysis of the
      glycolipid glucocerebroside to ceramide and glucose. Lysosomal storage of the
      substrate in cells of the reticuloendothelial system leads to multisystemic
      manifestations, including involvement of the liver, spleen, bone marrow, lungs,
      and nervous system. Patients with GD have highly variable presentations and
      symptoms that, in many cases, do not correlate well with specific genotypes.
      Almost 300 unique mutations have been reported in the glucocerebrosidase gene
      (GBA), with a distribution that spans the gene. These include 203 missense
      mutations, 18 nonsense mutations, 36 small insertions or deletions that lead to
      either frameshifts or in-frame alterations, 14 splice junction mutations, and 13
      complex alleles carrying two or more mutations in cis. Recombination events with
      a highly homologous pseudogene downstream of the GBA locus also have been
      identified, resulting from gene conversion, fusion, or duplication. In this
      review we discuss the spectrum of GBA mutations and their distribution in the
      patient population, evolutionary conservation, clinical presentations, and how
      they may affect the structure and function of glucocerebrosidase.

PMID- 18338394
TI  - Obesity in long-term survivors of childhood acute lymphoblastic leukemia.
AB  - BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) with current cure rates
      reaching 80% emphasizes the necessity to determine treatment related long-term
      effects. The present study examines the prevalence of and the risk factors for
      overweight and obesity in a cohort of ALL survivors treated and living in the
      French speaking part of Switzerland. METHODS: In this retrospective two-center
      study, height and weight of 54 patients diagnosed with ALL in first complete
      remission and treated with chemotherapy only were recorded at specified time
      points during treatment and off-therapy. Body mass index (BMI) and its age- and
      gender-adjusted standard deviation score (BMI-SDS) were calculated for the
      patients and their parents separately. Overweight and obesity were defined by a
      threshold of BMI-SDS >1.645 and BMI-SDS >1.96, respectively. RESULTS: At last
      follow-up, 16 (30%) of the 54 survivors were overweight and 10 (18%) were obese.
      The off-treatment period was most at risk with 11 of the 16 becoming overweight
      and 9 of the 10 becoming obese during that period. Overweight/obesity at
      diagnosis and abnormal maternal BMI were significantly associated with abnormal
      weight at follow-up, while age at diagnosis, gender, cumulative dose of steroids
      and paternal BMI showed no association. CONCLUSIONS: Consistent with published
      evidence from other regions of the developed and developing world, there is a
      significant prevalence of obesity in young ALL survivors in the French speaking
      part of Switzerland. Factors significantly associated with this late effect were
      mostly related to the familial background rather than to the treatment
      components.

PMID- 18338395
TI  - Treatment of juvenile xanthogranuloma.
AB  - Juvenile xanthogranuloma (JXG) is generally a benign, self-limited histiocytic
      disorder of the skin. We report two cases of multisystem JXG presenting with
      clinical features more commonly seen in Langerhans cell histiocytosis (LCH),
      including diabetes insipidus and lytic bony lesions. Histologically, the skin
      lesions demonstrated a histiocytic dermal infiltrate that stained for CD-68, but
      S-100 and CD1a stains were negative. Treatment according to LCH-based
      chemotherapy regimens resulted in prompt resolution of symptoms. A literature
      review of multisystem JXG cases treated with chemotherapy suggests that
      symptomatic patients can successfully be treated with LCH-based regimens that
      include both corticosteroids and vinca alkaloids.

PMID- 18338396
TI  - Central neurocytoma responsive to topotecan, ifosfamide, carboplatin.
AB  - A 5-year-old male presented with spinal cord drop metastasis from a recurrent
      neurocytoma. Topotecan (0.5 mg/m(2)) and carboplatin (250 mg/m(2)) were
      administered on days 1-3 and ifosfamide (1,800 mg/m(2)) on days 1-5, every 21
      days, for three cycles and resulted in complete response without severe
      complications. A literature review yielded 20 patients with central neurocytoma
      but no complete responses. The complete response of central neurocytoma to
      chemotherapy only reported here should be helpful to those caring for patients
      with this rare tumor.

PMID- 18338397
TI  - Epidemiology of Langerhans cell histiocytosis: onwards and upwards!

PMID- 18338398
TI  - Aspergillus tracheobronchitis following a fungal tongue nodule.

PMID- 18338399
TI  - Health-related quality of life in sickle cell disease.
AB  - Advances in drug therapy, hematopoietic stem cell transplantation, and technology
      have improved the morbidity and survival for those with sickle cell disease. The
      effect of this modern therapy on the health-related quality of life (HRQL) of
      those with sickle cell disease is not known. HRQL provides an assessment of how
      an illness, its complications, and its treatment are experienced by a patient.
      This review will examine prior work in HRQL in sickle cell disease and the
      rationale for utilizing HRQL as an outcome to measure impact of treatment. In
      addition, issues to consider when reporting HRQL will be presented.

PMID- 18338400
TI  - Expression and localization of the prion protein PrP(C) in the olfactory system
      of the mouse.
AB  - The normal physiological function of the prion protein PrP(C) remains elusive
      despite its widespread expression, particularly throughout the nervous system. A
      critical step toward identifying its function is to precisely localize its
      pattern of expression. Historically, the immunolocalization of PrP(C) has proved
      to be notoriously difficult and nonconsensual. We have thus undertaken a detailed
      expression analysis by means of a combination of in situ hybridization, knockout
      mice, and immunohistochemistry, using recently generated highly specific
      antibodies. We have attempted to accurately localize PrP(C) expression in a
      tissue that is highly structured and of crucial behavioral importance to mice,
      the olfactory system. We found that PrP(C) was expressed in both peripheral and
      central neurons of the olfactory system and that its distribution was axonal
      specific in both olfactory sensory neurons of the olfactory epithelium and mitral
      cells of the olfactory bulb. Our detailed expression analysis and the axonal
      localization we observed may provide important hints toward potential functions
      of PrP(C).

PMID- 18338401
TI  - Diagnostics in the shadow of HIV epidemics.
AB  - As part of the effort to promote elimination of global health care disparities,
      this special supplement compiled 19 articles about practical diagnostic cytometry
      to recognize the recent achievements of laboratory scientists working in the
      shadow of the HIV/AIDS epidemics in resource limited settings. First, the
      clinical significance, diagnostic utility (as governed by international
      guidelines), and the historical perspectives of CD4+ T cell enumeration are
      reviewed. Then successful large-scale implementations of cost-effective CD4
      counting are described for parts of Africa, USA, and the Caribbean. These
      activities are linked with both the training of personnel in fledgling
      laboratories as well as with external quality assessment implementations. Some of
      the more recent solutions related to pediatric CD4 testing using CD4% values are
      covered. Nevertheless, the need for further simplification and parsimony is still
      immense, and the potential solutions are catalogued in the articles written by
      experts operating in truly challenging rural environments. Cytometry is
      considered to be an expandable flexible technology for other assays beyond CD4
      assessment, particularly within organized laboratory services in the Third World.
      These include haematological measurements, CD38/CD8 lymphocyte activation for
      viral load-related assessments, diagnosis of active tuberculosis and malaria, and
      bead-based serological assays for a variety of infectious diseases. The
      development and support of these emerging technologies by affluent countries is
      not entirely altruistic but is likely to be beneficial for both the Third and the
      First Worlds.

PMID- 18338402
TI  - Hypothesis of active components in volatile oil from a Chinese herb formulation,
      'Shao-Fu-Zhu-Yu decoction', using GC-MS and chemometrics.
AB  - Traditional Chinese medicine (TCM) with few or no side effects has increasingly
      attracted attention all over the world. However, the bioactive components and the
      therapeutic mechanisms are usually not understood because of the complex chemical
      compositions of these medicines. In this paper, GC-MS coupled with a chemometric
      method was developed for analysis of active components in volatile oil from a
      Chinese herb formulation, "Shao-Fu-Zhu-Yu Decoction". The volatile oils, obtained
      by hydrodistillation from "Shao-Fu-Zhu-Yu Decoction" (SFZYD) and its constituent
      herbs with abundant volatile oil (Angelica sinensis, Ligusticum chuanxiong,
      Cinnamomum cassia, Foeniculum vulgare, Zingiber officinale), were chemically
      analyzed using GC-MS and bioassayed using oxytocin-induced uterine contraction
      assay in vitro. Then, a mathematic model relating the chemical compositions and
      their activities in inhibiting mice uterine contraction was established for
      hypothesis of the bioactive compounds based on chemometrics. As a result, nine
      compounds which might contribute to the inhibition of oxytocin-induced uterine
      contraction were selected, and the activities of some of them were further
      confirmed by our experiments and/or the literature. The data suggest that the
      developed method is helpful for screening bioactive components from complex
      mixtures, such as the extracts of TCM.

PMID- 18338403
TI  - Determination of montelukast sodium by capillary electrophoresis.
AB  - This work verifies the potential of CE in the analysis of significant impurities
      of montelukast sodium - an active ingredient for the treatment of bronchial
      asthma. Using 20 mM borate buffer pH 9.2 with 10 mM SDS and 10 mM (2
      hydroxypropyl)-gamma-CD (2HP-gamma-CD) it was possible to separate montelukast
      and several impurities, including its cis-isomer, after exposure to light and
      oxygen. The obtained method surpasses a chromatographic method for montelukast
      sodium in terms of time of analysis (9 min of CE analysis vs. 35 min HPLC) and
      efficiency (CE offered over 900 000 theoretical plates for montelukast). Good
      repeatability of the method was supported by the low % RSD for the migration time
      of montelukast (0.53%). For the first time, the capillary electrophoretic method
      was employed for temporal study of the degradation of montelukast. The results
      showed that degradation of montelukast and the formation of the cis-isomer mainly
      occurred during the first 2 days of exposure, and occurred to a higher degree
      when there was no contact with the air (oxygen) in the exposed sample.

PMID- 18338404
TI  - Determination of triazine herbicides in fruits and vegetables using dispersive
      solid-phase extraction coupled with LC-MS.
AB  - A simple, rapid, and sensitive liquid chromatography-mass spectrometry (LC-MS)
      method was successfully developed for the determination of three chloro-s
      triazine herbicides, viz. atrazine, simazine, and propazine, two thiomethyl-s
      triazine ones, viz. ametryn and prometryn, and prometon in fruits and vegetables.
      The instrumental parameters affecting LC separation and MS detection were
      investigated and the best conditions were selected. Samples were extracted and
      purified by dispersive solid-phase extraction (dispersive-SPE) with a primary
      secondary amine sorbent. Three typical representative samples (luffa, broad bean,
      and grape) were selected to investigate the effect of different matrices on
      pesticide recoveries and assay precision after spiking at 0.05 mg/kg. Matrix
      composition did not interfere significantly with the determination of these
      pesticides. The recoveries were, with a few exceptions, in the range of 80-110%
      with relative standard deviations less than 10% (n = 5). In addition, this method
      was also applied to 21 different kinds of agriculture products collected from the
      local market, and two of the six triazines could be detected and quantified.

PMID- 18338405
TI  - Ultra-performance LC/TOF MS analysis of medicinal Panax herbs for metabolomic
      research.
AB  - In this study, metabolite profiling of five medicinal Panax herbs including Panax
      ginseng (Chinese ginseng), Panax notoginseng (Sanchi), Panax japonicus (Rhizoma
      Panacis Majoris), Panax quinquefolium L. (American ginseng), and P. ginseng
      (Korean ginseng) were performed using ultra-performance LC-quadrupole TOF MS
      (UPLC-QTOFMS) and multivariate statistical analysis technique. Principal
      component analysis (PCA) of the analytical data showed that the five Panax herbs
      could be separated into five different groups of phytochemicals. The chemical
      markers such as ginsenoside Rf, 20(S)-pseudoginsenoside F11, malonyl gisenoside
      Rb1, and gisenoside Rb2 accountable for such variations were identified through
      the loadings plot of PCA, and were identified tentatively by the accurate mass of
      TOFMS and partially verified by the available reference standards. Results from
      this study indicate that the proposed method is reliable for the rapid analysis
      of a group of metabolites present in herbal medicines and other natural products
      and applicable in the differentiation of complex samples that share similar
      chemical ingredients.

PMID- 18338406
TI  - beta-Sitosterol enhances tamoxifen effectiveness on breast cancer cells by
      affecting ceramide metabolism.
AB  - The objective of this study was to investigate the effects of the dietary
      phytosterol beta-sitosterol (SIT) and the antiestrogen drug tamoxifen (TAM) on
      cell growth and ceramide (CER) metabolism in MCF-7 and MDA-MB-231 human breast
      cancer cells. The MCF-7 and MDA-MB-231 cell lines were studied as models of
      estrogen receptor positive and estrogen receptor negative breast cancer cells.
      Growth of both cell lines as determined using the sulforhodamine B assay was
      inhibited by treatment with 16 microM SIT but only MCF-7 cell growth was
      inhibited by treatment with 1 microM TAM. The combination of SIT and TAM further
      inhibited growth in both cell lines, most significantly in MDA-MB-231 cells. CER
      is a proapoptotic signal and CER levels were increased in both MCF-7 and MDA-MB
      231 cells by individual treatment with SIT and TAM and the combined treatment
      raised cellular CER content even further. SIT and TAM raised CER levels by
      different means. SIT potently activated de novo CER synthesis in both MCF-7 and
      MDA-MB-231 cells by stimulating serine palmitoyltransferase activity; whereas TAM
      promoted CER accumulation in both cell types by inhibiting CER glycosylation.
      These results suggest that the combination regimen of dietary SIT and TAM
      chemotherapy may be beneficial in the management of breast cancer patients.

PMID- 18338407
TI  - Maternal dietary habits and mycotoxin occurrence in human mature milk.
AB  - During 2006, 82 samples of human mature milk were collected at Italian hospitals
      and checked for aflatoxin M1 (AFM1) and ochratoxin A (OTA) by immunoaffinity
      column extraction and HPLC. AFM1 was detected in four (5%) of milk samples
      (ranging from < 7 ng/L to 140 ng/L; mean level: 55.35 ng/L); OTA was detected in
      61 (74%) of milk samples (ranging from < 5 ng/L to 405 ng/L; mean level: 30.43
      ng/L. OTA levels were significantly higher (p less, not double equals 0.05) in
      milk of habitual consumers of bread, bakery products and cured pork meat. No
      other statistically significant differences were observed although habitual
      consumers of pasta (p = 0.059), cookies (p = 0.061) and juices (p = 0.063) had
      mean contamination values of OTA higher than the moderate consumer. The very few
      AFB1 positive samples did not allow statistical comparisons. The present study
      confirms that the occurrence of OTA in human milk is related to maternal dietary
      habits. The findings support the possibility of dietary recommendations to woman,
      during pregnancy and lactation, aimed to tentatively reduce the OTA contamination
      of human milk.

PMID- 18338408
TI  - Legumin allergens from peanuts and soybeans: effects of denaturation and
      aggregation on allergenicity.
AB  - Legumin proteins Ara h 3 from peanuts and glycinin from soybeans are increasingly
      described as important allergens. The stability of an allergen's IgE binding
      capacity towards heating and digestion is considered an important characteristic
      for food allergens. We investigated the effects of heating and digestion on the
      IgE binding of Ara h 3 and glycinin. Both proteins are relatively stable to
      denaturation, having denaturation temperatures ranging from 70 to 92 degrees C,
      depending on their quaternary structure and the ionic strength. Aggregates were
      formed upon heating, which were partly soluble for glycinin. Heating slightly
      decreased the pepsin digestion rate of both allergens. However, heating did not
      affect the IgE binding capacity of the hydrolyzates, as after only 10 min of
      hydrolysis no IgE binding could be detected any more in all samples. Peanut
      allergen Ara h 1, when digested under equal conditions, still showed IgE binding
      after 2 h of hydrolysis. Our results indicate that the IgE binding capacity of
      legumin allergens from peanuts and soybeans does not withstand peptic digestion.
      Consequently, these allergens are likely unable to sensitize via the gastro
      intestinal tract and cause systemic food allergy symptoms. These proteins might
      thus be less important allergens than was previously assumed.

PMID- 18338409
TI  - Synthetic scope of Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions: an
      application to reduction of allylic alcohols by a sequential process of
      isomerization/Meerwein-Ponndorf-Verley-type reduction.
AB  - Reduction of allylic alcohols can be promoted efficiently by the supported
      ruthenium catalyst Ru(OH)x/Al2O3. Various allylic alcohols were converted to
      saturated alcohols in excellent yields by using 2-propanol without any additives.
      This Ru(OH)x/Al2O3-catalyzed reduction of a dienol proceeds only at the allylic
      double bond to afford the corresponding enol, and chemoselective isomerization
      and reduction can be realized under similar conditions. The catalysis is truly
      heterogeneous and the high catalytic performance can be maintained during at
      least three recycles of the Ru(OH)x/Al2O3 catalyst. The transformation of allylic
      alcohols to saturated alcohols consists of three sequential reactions: oxidation
      of allylic alcohols to alpha,beta-unsaturated carbonyl compounds; reduction of
      alpha,beta-unsaturated carbonyl compounds to saturated carbonyl compounds; and
      reduction of saturated carbonyl compounds to saturated alcohols.

PMID- 18338410
TI  - Synthesis and properties of DNA complexes containing 2,2,6,6-tetramethyl-1
      piperidinoxy (TEMPO) moieties as organic radical battery materials.
AB  - We report here the first example of organic radical battery with DNA. Though
      there is a growing interest in DNA/cationic-lipid complexes as promising gene
      delivery vehicles, few efforts have been focused on the use of such complexes as
      advanced materials for organic optoelectronic applications. The present article
      describes how substitution of the sodium counter cation of DNA with cationic
      amphiphilic lipid(1-4) provided novel DNA-lipid complexes that contain TEMPO
      radicals, in which the actual mole ratio of phosphate to lipid was 1:0.84 to
      1:0.16. All the TEMPO-containing DNA-lipid complexes displayed reversible two
      stage charge/discharge processes, the discharge capacities of which were 40.5
      60.0 A h kg(-1). In particular, the capacity of a DNA-lipid(3)-based cell reached
      60.0 A h kg(-1), which corresponds to 192 % relative to its theoretical value for
      the single-electron one-stage process, indicating a two-electron process.

PMID- 18338411
TI  - Mononuclear ruthenium hydride species versus ruthenium nanoparticles: the effect
      of silane functionalities on silica surfaces.

PMID- 18338412
TI  - Alkylzinc hydrazides: self-assembly of hexanuclear ring systems in acetonitrile.

PMID- 18338413
TI  - Molecular symmetry and solution-phase structure interrogated by hyper-Rayleigh
      depolarization measurements: elaborating highly hyperpolarizable D2-symmetric
      chromophores.

PMID- 18338414
TI  - Dichotomic reactivity of a stable silylene toward terminal alkynes: facile C-H
      bond insertion versus autocatalytic formation of silacycloprop-3-ene.

PMID- 18338415
TI  - A straightforward route to helically chiral N-heteroaromatic compounds: practical
      synthesis of racemic 1,14-diaza[5]helicene and optically pure 1- and 2
      aza[6]helicenes.

PMID- 18338416
TI  - Enantioselective palladium-catalyzed trimethylenemethane [3+2] cycloadditions.

PMID- 18338417
TI  - Transfer semihydrogenation of alkynes catalyzed by a zero-valent palladium N
      heterocyclic carbene complex.

PMID- 18338418
TI  - Effects of guanidinium-phosphate hydrogen bonding on the membrane-bound structure
      and activity of an arginine-rich membrane peptide from solid-state NMR
      spectroscopy.

PMID- 18338419
TI  - Molecular diffusion measurement in lipid bilayers over wide concentration ranges:
      a comparative study.
AB  - Molecular diffusion in biological membranes is a determining factor in cell
      signaling and cell function. In the past few decades, three main fluorescence
      spectroscopy techniques have emerged that are capable of measuring molecular
      diffusion in artificial and biological membranes at very different concentration
      ranges and spatial resolutions. The widely used methods of fluorescence recovery
      after photobleaching (FRAP) and single-particle tracking (SPT) can determine
      absolute diffusion coefficients at high (>100 microm(-2)) and very low surface
      concentrations (single-molecule level), respectively. Fluorescence correlation
      spectroscopy (FCS), on the other hand, is well-suited for the intermediate
      concentration range of about 0.1-100 microm(-2). However, FCS in general requires
      calibration with a standard dye of known diffusion coefficient, and yields only
      relative measurements with respect to the calibration. A variant of FCS, z-scan
      FCS, is calibration-free for membrane measurements, but requires several
      experiments at different well-controlled focusing positions. A recently
      established FCS method, electron-multiplying charge-coupled-device-based total
      internal reflection FCS (TIR-FCS), referred to here as imaging TIR-FCS (ITIR
      FCS), is also independent of calibration standards, but to our knowledge no
      direct comparison between these different methods has been made. Herein, we seek
      to establish a comparison between FRAP, SPT, FCS, and ITIR-FCS by measuring the
      lateral diffusion coefficients in two model systems, namely, supported lipid
      bilayers and giant unilamellar vesicles.

PMID- 18338420
TI  - Formation of reverse micelles in a room-temperature ionic liquid.

PMID- 18338421
TI  - Tuning the geometric structure by doping silicon clusters.

PMID- 18338422
TI  - Substituted pyrazolo[3,4-b]pyridines as potent A1 adenosine antagonists:
      synthesis, biological evaluation, and development of an A1 bovine receptor model.
AB  - Sixty-eight new substituted pyrazolo[3,4-b]pyridine derivatives were synthesized
      and tested for enriching a library of active A(1) adenosine receptor (AR)
      antagonists belonging to the same class. These compounds were also used as an
      external test set to check the reliability of a 3D QSAR model recently reported
      by us. To investigate the binding mode of pyrazolopyridine derivatives, a model
      of the bovine A(1)AR (bA(1)AR) was developed by a novel homology modeling
      approach and used to evaluate the main interactions of the ligands with the
      receptor through docking studies. Results suggest important interactions of the
      ligands mainly with L3.33(88), T3.36(91), Q3.37(92) and H6.52(251), in agreement
      with mutagenesis data. The racemic mixture of the most active compound was
      separated into the corresponding enantiomers which showed a bA(1)AR affinity in
      the nanomolar range, with the R enantiomer sevenfold more active than the S
      enantiomer, according to results derived from calculations on the receptor model.
      Analysis of the bovine/human A(1)AR affinity profile of ligands supported the
      hypothesis that such receptors should be characterized by a different size of
      their binding site, responsible for the different affinity of the antagonists.

PMID- 18338423
TI  - Molecular recognition of small-cell lung cancer cells using aptamers.
AB  - Early diagnosis is the way to improve the rate of lung cancer survival, but is
      almost impossible today due to the lack of molecular probes that recognize lung
      cancer cells sensitively and selectively. We developed a new aptamer approach for
      the recognition of specific small-cell lung cancer (SCLC) cell-surface molecular
      markers. Our approach relies on cell-based systematic evolution of ligands by
      exponential enrichment (cell-SELEX) to evolve aptamers for whole live cells that
      express a variety of surface markers representing molecular differences among
      cancer cells. When applied to different lung cancer cells including those from
      patient samples, these aptamers bind to SCLC cells with high affinity and
      specificity in various assay formats. When conjugated with magnetic and
      fluorescent nanoparticles, the aptamer nanoconjugates could effectively extract
      SCLC cells from mixed cell media for isolation, enrichment, and sensitive
      detection. These studies demonstrate the potential of the aptamer approach for
      early lung cancer detection.

PMID- 18338424
TI  - A structural model of the membrane-bound aromatic prenyltransferase UbiA from E.
      coli.
AB  - The membrane-bound enzyme 4-hydroxybenzoic acid oligoprenyltransferase (ubiA)
      from E. coli is crucial for the production of ubiquinone, the essential electron
      carrier in prokaryotic and eukaryotic organisms. On the basis of previous
      modeling analyses, amino acids identified as important in two putative active
      sites (1 and 2) were selectively mutated. All mutants but one lost their ability
      to form geranylated hydroxybenzoate, irrespective of their being from active site
      1 or 2. This suggests either that the two active sites are interrelated or that
      they are in fact only one site. With the aid of the experimental results and a
      new structure-based classification of prenylating enzymes, a relevant 3D model
      could be developed by threading. The new model explains the substrate
      specificities and is in complete agreement with the results of site-directed
      mutagenesis. The high similarity of the active fold of UbiA-transferase to that
      of 5-epi-aristolochene synthase (Nicotiana tabacum), despite a low homology,
      allows a hypothesis on a convergent evolution of these enzymes to be formed.

PMID- 18338425
TI  - Synthetic strategy of nonreducing iterative polyketide synthases and the origin
      of the classical "starter-unit effect".

PMID- 18338426
TI  - Orally disintegrating olanzapine and potential differences in treatment-emergent
      weight gain.
AB  - Several papers and communications have reported possible weight reduction or less
      weight gain when patients start or switch to orally disintegrating olanzapine, as
      contrasted with standard oral olanzapine tablets. In this paper, the current
      literature is reviewed and hypothesized mechanisms of action are discussed. The
      data are still preliminary and mechanisms of action are not well understood.
      Randomized controlled trials are needed to further evaluate change in weight
      during treatment with orally disintegrating olanzapine.

PMID- 18338427
TI  - Imaging of gynecological disease (3): clinical and ultrasound characteristics of
      granulosa cell tumors of the ovary.
AB  - OBJECTIVES: To describe the clinical and ultrasound characteristics of granulosa
      cell tumors (GCTs) of the ovary, and to define the ultrasound appearance of GCTs
      based on pattern recognition. METHODS: Databases of four gynecological ultrasound
      centers were searched to identify patients with histologically proven GCTs who
      had undergone a standard preoperative ultrasound examination. RESULTS: A total of
      23 women with confirmed GCT were identified. Twelve (52%) women were
      postmenopausal, nine (39%) were of fertile age and two (9%) were prepubertal.
      Clinical symptoms were abdominal distension (7/23, 30%), pain (5/23, 22%) and
      irregular vaginal bleeding (6/23, 26%). Seven patients (30%) were asymptomatic.
      Endometrial pathology was found in 54% (7/13) of the patients from whom
      endometrial biopsies were taken. On ultrasound scan 12/23 (52%) masses were
      multilocular-solid, 9/23 (39%) were purely solid, one mass (4%) was unilocular
      solid and one mass was multilocular (4%). Multilocular and multilocular-solid
      cysts typically contained large numbers of small locules (> 10). The echogenicity
      of the cyst content was most often mixed (6/16, 38%) or low level (7/16, 44%).
      Papillary projections were found in only four women (17%). The GCTs were large
      tumors with a median largest diameter of 102 (range, 37-242) mm and manifested
      moderate or high color content at color Doppler examination (color score 3 in
      13/23 tumors (57%); color score 4 in 8/23 tumors (35%)). CONCLUSIONS: At
      ultrasound examination, most GCTs are large multilocular-solid masses with a
      large number of locules, or solid tumors with heterogeneous echogenicity of the
      solid tissue. Hemorrhagic components are common and increased vascularity is
      demonstrated at color/power Doppler ultrasound examination. The hyperestrogenic
      state that is created by the tumor often causes endometrial pathology with
      bleeding problems as a typical associated symptom.

PMID- 18338428
TI  - Serving two gods.

PMID- 18338429
TI  - [Readers' letters concerning F. Keller et al: "Financial incentives and
      dialysis"].

PMID- 18338430
TI  - Aptivus capsules granted full FDA approval.

PMID- 18338431
TI  - European CHMP issues positive opinion for Atripla.

PMID- 18338432
TI  - More bad news on vaccine trials.

PMID- 18338433
TI  - European license for Viracept re-established by EC.

PMID- 18338434
TI  - Alternative administration options for Fuzeon.

PMID- 18338435
TI  - G.I. Jonny declares war on ignorance.

PMID- 18338436
TI  - Oral AIDS vaccine used in Thailand.

PMID- 18338437
TI  - RANZCP Exemptions Candidates   Examination.

PMID- 18338438
TI  - Inadequate training in the   psychotherapies.

PMID- 18338439
TI  - [Respiratory infections, always a relevant subject].

PMID- 18338440
TI  - Longitudinal study of umbilical and portal venous blood flow to the fetal liver:
      low pregnancy weight gain is associated with preferential supply to the fetal
      left liver lobe.
AB  - Recent data suggest that umbilical venous perfusion of the fetal liver has an
      important influence on fetal growth and postnatal liver function, and that
      maternal factors in late pregnancy modify this circulation. In a longitudinal
      study of 160 low-risk pregnancies, we determined how umbilical and portal venous
      blood flows to the fetal liver changed during gestation, and examined the
      hypothesis that maternal body mass index and pregnancy weight gain influenced
      fetal liver blood flows. We measured blood flows in the umbilical and portal
      veins, left portal branch, and ductus venosus using ultrasound. Normalizing for
      estimated fetal weight, fetal liver total venous blood flow fell from 84 to 57
      mL. min(-1). kg(-1) during 21-39 wk of gestation; toward term the portal
      contribution increased (from 14 to 20%) and the umbilical contribution fell,
      whereas distribution between the left and right liver lobes was stable, 60%/40%.
      Greater flow of nutrient-rich umbilical venous blood to the liver was associated
      with higher birth weight and neonatal ponderal index. Maternal body mass index
      was not related to fetal liver blood flows, but low pregnancy weight gain
      strongly influenced flow distribution between the right and left liver lobes,
      sparing the left lobe and increasing the difference between lobes by 16%.

PMID- 18338441
TI  - Longitudinal study of the symptom checklist 90-revised in multiple sclerosis
      patients.
AB  - The current study examined the 3-year longitudinal course of psychopathology
      reported by 53 definite MS patients, then assessed for clinical elevations.
      Across SCL-90-R scales, only 9-21% of patients' scores changed. Intercorrelations
      among Time 1 and Time 2 were significant (p < .01). Clinical elevations on the
      scales ranged from 26% (anxiety) to 52% (somatization). Consistent with studies
      of depression, results demonstrated that other types of psychopathology are very
      stable over time. Because a relatively high percentage of patients displayed
      clinical elevations across the scales over time, this study suggests that the
      stability of psychopathology in MS patients is of clinical concern.

PMID- 18338442
TI  - Assigning qualitative descriptions to test scores in neuropsychology: forensic
      implications.
AB  - Board-certified neuropsychologists were surveyed and asked to assign a
      descriptive label (e.g., superior, average, normal, impaired) to 12 different
      standard scores (SS), from 50 to 130, of a memory test based on a brief case
      scenario. Surveys were returned by 49% (n = 110) of the target sample. The mean
      number of different classification labels assigned by participants to each of the
      12 SS was 14 and ranged from 6 (for SS = 95) to 23 (for SS = 50). The mean
      percentages of participants who assigned the one or two most frequently used
      labels within each SS were 52.5% and 70.7%, respectively. Results revealed
      variable uniformity in assigning descriptive labels to specific standard scores,
      with significantly greater variability for SS in the lower half of the
      distribution and with applying impairment rather than normative labels.
      Professional and forensic implications are discussed.

PMID- 18338443
TI  - Final report of outcomes from the National Consensus Conference for Vaccine
      Preventable Diseases in Canada, June 12-14, 2005 - Quebec City, Quebec.

PMID- 18338444
TI  - PLK1 and survivin in diffuse large B-cell lymphoma.

PMID- 18338445
TI  - Editorial: 'Thousands starving in U.K. hospitals'; letter 2.

PMID- 18338446
TI  - Complexity of treatment decisions with older patients.

PMID- 18338447
TI  - Lack of access to out-of-hours endoscopy: implications for trainees too.

PMID- 18338448
TI  - HFMA profile. 'To be an indispensable resource for healthcare finance'.

PMID- 18338449
TI  - Ethics of surgical innovation and research: knowledge and attitude of surgeons.

PMID- 18338450
TI  - Unison takes Monitor to court in wake of income cap silence.

PMID- 18338451
TI  - Who foots the bill: establishing responsibility for patient care.

PMID- 18338452
TI  - Mental software.

PMID- 18338453
TI  - Local control puts boards under the spotlight.

PMID- 18338454
TI  - Data briefing. Patient reports are simple and useful.

PMID- 18338455
TI  - Valuing people now. Value for many.

PMID- 18338456
TI  - Here's to you, Ms Robinson. Interview by Stuart Shepherd.

PMID- 18338459
TI  - The presence of family members during cardiopulmonary resuscitation.

PMID- 18338460
TI  - Brain activity accompanying perception of implied motion in abstract paintings.
AB  - Early 20th century artists including Duchamp and Balla tried to portray moving
      objects on a static canvas by superimposing objects in successive portrayals of
      an action. We investigated whether implied motion in those paintings is
      associated with activation of motion-sensitive area MT+. In Experiment 1, we
      found that observers rated these kinds of paintings higher in portraying motion
      than they did other abstract paintings in which motion is not intended. We also
      found that observers who had previously experienced abstract paintings with
      implied motion tended to give higher motion ratings to that class of paintings.
      In Experiment 2, we used functional magnetic resonance imaging (fMRI) to measure
      brain activity of observers while viewing abstract paintings receiving the
      highest and the lowest motion rating scores in Experiment 1. We found MT+, but
      not primary visual cortex (V1), showed greater BOLD responses to abstract
      paintings with implied motion than to abstract paintings with little motion
      impression, but only in observers with prior experience viewing those kinds of
      paintings. These results imply that the neural machinery ordinarily engaged
      during perception of real visual motion is activated when people view paintings
      explicitly designed to convey a sense of visual motion. Experience, however, is
      necessary to achieve this sense of motion.

PMID- 18338461
TI  - Wales and the National Health Service.

PMID- 18338462
TI  - The long shadow of segregation.

PMID- 18338463
TI  - Proceedings of the 16th GP2A (Group of Medicinal Chemists of the Atlantic Arc)
      Conference, Bordeaux, France, September 2007.

PMID- 18338464
TI  - Civilizing the natives: marriage in Post-Apartheid South Africa.

PMID- 18338465
TI  - [The history of medicine in Czech lands, 1993-2000].

PMID- 18338466
TI  - Protracted national conflict and fertility change: Palestinians and Israelis in
      the twentieth century.

PMID- 18338467
TI  - [Proceedings of the National Conference on Malignant Mesotheliomas in the Lower
      Iseo Lake Area, 22 May 2006, Iseo, Italy].

PMID- 18338469
TI  - [Chronic kidney disease and renal damage in elderly age].

PMID- 18338470
TI  - [A clinical research of AADC gene therapy for Parkinson's disease].

PMID- 18338471
TI  - Deplorable state of blood transfusion services in India.

PMID- 18338472
TI  - A study on smoking habits among slum dwellers and the impact on health and
      economics.
AB  - To assess the impact on health from smoking with economic implications with major
      emphasis given to see whether passive smoking is an established outcome and if it
      is, how much additional burden of the disease is put on the smokers' families and
      consequently how much extra economic cost is put on such families, a study was
      conducted in a slum area of Howrah Municipal Corporation (HMC) on approximately
      3000 families, which were randomly selected. Data was collected in relation to
      the socio-economic status, family members, housing with water and environmental
      sanitation, smoking habit, energy used for cooking, health awareness, follow-up
      of episodes of diseases of all ages, their remedial action taken and estimation
      of economic burden of the disease due to smoking (active and passive). There was
      a statistically significant difference in disease pattern between smokers' family
      and non-smokers' family especially with relation to chronic obstructive pulmonary
      disease, coronary heart disease, acute respiratory infections, common cold,
      hypertension and peptic ulcer (p<0.05). Also it was observed that with increasing
      years (1st, 2nd, 3rd years), the number of cases in each disease group gradually
      increased. This can be attributed to the effect of passive smoking especially
      when environmental conditions and socio-economic variants are same in both
      groups. Cost analysis of the illness episodes in the smokers' and non-smokers'
      families showed that there was a 3-fold difference in average annual expenditure
      between the families of the non-smokers and that of smokers and a 8-fold
      difference in work days lost. There was a 4-fold difference in annual expenditure
      on these diseases by the families. It is observed that when the total cost of
      smoking was included in the total expenditure, there was a 12-fold increase in
      annual expenditure between smokers' and non-smokers' families. The study
      conclusively proves that there are ill effects on health both from active and
      passive smoking. It is also demonstrated here that apart from economic
      implications due to direct smoking, the economic loss has been added to smokers'
      families due to passive smoking.

PMID- 18338473
TI  - Tuberculosis of lower cervical spine--a prospective study.
AB  - Tuberculosis was a leading cause of mortality in the beginning of the twentieth
      century. Tuberculosis of the spine is one of the oldest diseases afflicting
      humans. A prospective study was carried out among 45 cases of tuberculosis of
      lower cervical spine and an attempt was made to highlight some of its features.
      Pain and stiffness were important and dominant complaints. Commonest level
      affected was C5-C6 vertebrae. The overall incidence of cord compression was 37.8
      per cent. The commonest modality of treatment was antituberculous drugs, anterior
      excision of diseased bone and tricortical bone grafting. This regime rapidly
      relieves pain, compressive respiratory symptoms due to large abscess and
      neurological deficit.

PMID- 18338474
TI  - A study of prophylactic use of 15-methyl prostalglandin F2alpha in the active
      management of third stage of labour.
AB  - To compare active management of third stage of labour with 15-methyl
      prostaglandin F2alpha (PGF2alpha) and conventional management with
      methylergometrine as prophylaxis for postpartum hemorrhage, a randomised
      comparative study was carried out at Calcutta National Medical College and
      Hospital, Kolkata on 100 women. They were randomly allotted to one of the two
      groups. Group A included 50 women who received 15-methyl PGF2alpha (125 microg)
      intramusculary at the time of delivery of the anterior shoulder and group B
      included 50 women who underwent conventional management of the third stage of
      labour where methylergometrine 0.2 mg was given after delivery of placenta. Main
      outcome measured were duration of third stage, amount of bleeding and side
      effects. The present study showed that there were significent reduction of the
      duration of third stage as well as reduction of amount of bleeding particularly
      when 125 microg of 15-methyl PGF2alpha was given intramuscularly at the time of
      delivery of the anterior shoulder in comparison to coventional method of
      management of third stage of labour with methylergometrine. Placental expulsion
      occurred within 4 minutes in group A and 16.5 minutes in group B. The amount of
      bleeding following delivery was 95.6 ml in average in group A and 249.6 ml in
      average in group B. 15-methyl PGF2alpha (125 microg) is certainly effective in
      prevention of postpartum haemorrhage particularly in developing country like
      India where this complication contributes a major factor for maternal mortality.

PMID- 18338475
TI  - Clinical analysis of 40 cases of uterine rupture at Durgapur Subdivisional
      Hospital: an observational study.
AB  - Forty cases of uterine rupture that occurred at Durgapur Subdivisional Hospital
      during 5 years period from January, 1995 to December, 1999 were analysed for
      clinical observations. The incidence was 1:273; 77.5% were spontaneous, 15% were
      traumatic, and 7.5% had scar rupture. It was complete in 92.5% cases.
      Disproportion was responsible in 40% cases and malpresentation in 27.5% cases.
      Total hysterectomy was done in 30% cases, subtotal in 27.5% cases and rent repair
      in 42.5% of cases. Overall maternal mortality was 30% of which highest (41.2%)
      found in rent repair and lowest (16.6%) in total hysterectomy.

PMID- 18338476
TI  - Neuroplasticity--a paradigm shift in neurosciences.
AB  - Neuroplasticity is the phenomenon in brain where different stimuli lead to
      increase or decrease in the number of brain cells and remodelling of synapses.
      Neuroplasticity research has now established beyond doubt that instead being a
      static cell mass, our brain is actually a dynamic system of neural network that
      has the capability of significant growth under favourable circumstances. This
      obviously opens up new possibilities in treatment of disorders where neural loss
      or synaptic decay is major factor in molecular aetiopathogeneis. Neuroplasticity
      research unravels the way stress acts. Similarly it gives new hypothesis
      regarding depression and epilepsy. Novel therapeutic approaches based on
      neuroplastic findings are also discussed.

PMID- 18338477
TI  - Torsion of appendices epiploicae of the colon: a case report.
AB  - Torsion of the appendices epiploicae is a rare surgical entity. It has been
      described very rarely in the literature. A case of a 33-year-old female presented
      with acute pain abdomen in the right iliac fossa accompanied with vomiting. On
      per abdomen examination MacBurney's tenderness was elicited. On exploring the
      abdomen, the appendix was found to be normal. But one of the nearby appendices
      epiploicae was found to have undergone torsion. It was resected out and so also
      the appendix.

PMID- 18338478
TI  - Posthepatitis aplastic anaemia presenting only with bilateral vision loss.
AB  - Aplastic anaemia is pancytopenia with marrow hypocellularity. Hepatitis
      associated aplastic anaemia is a varient or aplastic anaemia that follows an
      acute attack of seronegative hepatitis. Here a case of hepatitis-associated
      aplastic anaemia presenting with sudden onset of severe simultaneous bilateral
      vision loss and without any other usual presenting signs is reported. Partial
      recovery of blood cell count occurred following immunosuppressive therapy.
      Posterior hyalodotmy helped rapid resolution of premacular subhyaloid
      haemorrhage. Although bilateral vision loss may rarely be the initial
      presentation of aplastic anaemia, no such report is known in hepatitis-associated
      aplastic anaemia. Posthepatitis vision loss needs careful investigation to
      exclude an underlying haematological disorder.

PMID- 18338479
TI  - Pseudohermaphrodite presented as an irreducible inguinal hernia.
AB  - Absence of antimuellerian hormone or defective functioning of antimullerian
      hormone type II receptors give rise to a type of male pseudohermaphroditism known
      as 'persistent muellerian duct syndrome'. Such patients are phenotypically male
      with 46 XY karyotype and well developed muellerian duct derivatives which may be
      intra-abdominal or may herniate in inguinal region giving rise to a condition
      called as 'hernia uterine inguinale'. Cryptorchidism, transverse testicular
      ectopia and hypospadias are few anomalies associated with this syndrome. Though
      orchidopexy while leaving the uterus and fallopian tube in situ is an accepted
      surgical management, compromisation of blood surply to the testes or the vas may
      occur as vasa efferentia are embedded in the wall of uterus.

PMID- 18338480
TI  - Adenosquamous carcinoma of oral cavity: a case report.
AB  - An elderly man presented with a pair of soft tissue swelling, one on upper and
      another on lower gums, with chest pain and respiratory distress.
      Histopathological examination of the biopsied material showed features suggestive
      of adenosquamous carcinoma, but CT-guided fine needle aspiration cytology from
      lung mass showed evidence of non-keratinising squamous cell carcinoma. This
      histologic dissimilarity between primary and metastatic tumour is a
      characteristic feature of the lesion. Palliative radiation was given as the
      patient was unfit for surgery, but his condition deteriorated rapidly and
      treatment had to be withdrawn.

PMID- 18338481
TI  - Complete perineal tear with rectal prolapse: an unusual case report.
AB  - The association of complete perineal tear and rectal prolapse is less reported in
      literature, although isolated complete perineal tear and the combinations of
      vaginal and rectal prolapse are not so unusual, where multiparity and
      unsupervised home deliveries are quiet common. An interesting case of long
      standing complete perineal tear with complete rectal prolapse is reported in a 60
      years old lady along with review of literature, discussing the management and
      follow-up of the condition.

PMID- 18338482
TI  - Risk stratification and utilisation of thrombo-embolism prophylaxis in a medical
      surgical ICU: a hospital-based study.
AB  - To assess the risk for venous thrombo-embolism (VTE) and the utilisation of VTE
      prophylaxis in an open medical-surgical intensive care unit (ICU), patients were
      admitted and enrolled to the ICU at a multispecialty, tertiary care teaching
      hospital in Mumbai, for an observational study during a 3-month period. Risk
      factors for VTE and methods of VTE prophylaxis used were noted. Risk
      stratification was done, and the consultants attending the ICUs filled a
      questionnaire about VTE awareness, preferences and usage of VTE prophylaxis
      methods and reasons for not using thromboprophylaxis. Of 580 admissions, 488 were
      included in the study. As per the risk stratification, thromboprophylaxis was
      indicated in 466 (95%). The study group had an average VTE risk of 5.74, with a
      mean risk of 6.48 in medical patients and 5.0 in surgical patients. The most
      common risk factors in medical patients were bed rest >72 hours (56%), age >60
      years (49.6%) and age 40-60 years (38.4%). Among surgical patients, the most
      common risk factors were major surgery (80.25%), central venous access (59.24%)
      and age 40-60 years (46.6%). Overall, VTE prophylaxis was used in 229 patients
      (47%), with 127 (55%) medical and 102 (45%) surgical patients. The most common
      methods of VTE prophylaxis used were elastic stockings (24.2%), low molecular
      weight heparin (15%) and low molecular weight heparin and stockings both (9.6%).
      Fear of bleeding was the commonest reason cited for the underutilisation of VTE
      prophylaxis. Almost half of all high-risk patients admitted to the ICU didn't
      receive any thromboprophylaxis. Consistent practice patterns of ICUs, and
      continuing medical education programmes addressing VTE prophylaxis will help
      improve the usage of VTE prophylaxis.

PMID- 18338483
TI  - Current cancer profiles of the Italian regions: should cancer incidence be
      monitored at a national level?

PMID- 18338484
TI  - Rectal injury in radical perineal prostatectomy.
AB  - OBJECTIVE: To report our experience in treating patients with rectal injury with
      radical perineal prostatectomy. METHODS: Medical charts of 176 patients submitted
      to radical perineal prostatectomy from 1996 to 2005 were reviewed to identify
      rectal problems. A review of rectal injury in prostatectomy is provided. RESULTS:
      Of 176 patients who underwent radical perineal prostatectomy, 10 (5.7%) had
      rectal injury and 4 (2.3%) presented rectal fistula. Two (1.1%) patients were
      submitted to colostomy. We discuss how to avoid and treat the complications.
      CONCLUSIONS: There is a real risk of rectal injury during radical perineal
      prostatectomy, particularly during the learning period or if the approach is not
      often performed. Fistula might occur, but colostomy is actually unnecessary and
      rare. A better understanding of the perineal anatomy and knowledge about the
      technique is recommended before practicing radical perineal prostatectomy.

PMID- 18338485
TI  - The relation of lymphoma and hepatitis B virus/hepatitis C virus infections in
      the region of East Black Sea, Turkey.
AB  - AIM AND BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are not
      only hepatotropic, but also lymphotropic viruses. Infections with these viruses
      induce chronic antigenicity and may stimulate clonal expansion of malignant B
      cell neoplasms. Moreover, these viruses can proliferate in lymphatic structures
      and bone marrow. However, the relationship between lymphomas and HBV/HCV
      infections is not clear. In our region of the East Black Sea, Turkey (the city of
      Trabzon), we intended to demonstrate a relation of lymphoma and HBV/HCV
      infections with a case-controlled study. METHODS: A total of 109 patients
      diagnosed with lymphoma between 2002-2005 in the Black Sea Technical University
      Hospital was investigated. Seventy-one patients had a high-grade and 38 patients
      a low-grade lymphoma. Hepatitis B surface antigen (HBsAg) and anti-HCV antibodies
      (anti-HCV Ab) were screened. The control group consisted of patients (n = 551)
      from other departments with diagnoses other than lymphoma. RESULTS: HBsAg was
      3.7% and anti-HCV Ab positivity was 2.8% in lymphoma patients, compared with
      control of 5.3%, 5.1%, respectively. There was no statistically significant
      difference between two groups (P = 0.7, OR = 0.69, 95% CI, 0.20-2.10; P = 0.4, OR
      = 0.53, 95% CI, 0.13-1.86, respectively). CONCLUSION: Our findings suggest that
      the incidence of HBV and HCV infections in lymphoma patients is no different than
      that of nonlymphoma patients. Therefore, no direct correlation can be deduced
      between lymphoma and HBV-HCV infections in our East Black Sea region of Turkey.

PMID- 18338486
TI  - Inappropriate doses of chemotherapy in Italian breast cancer patients enrolled in
      clinical trials.
AB  - AIMS AND BACKGROUND: The dose of delivered chemotherapy is important to evaluate
      the appropriateness of the anticancer treatment. This aspect has been scarcely
      studied in Italy. About 7 years ago, the Italian Group for Antiemetic Research
      (IGAR) published a large controlled study on the effectiveness of different
      antiemetic prophylaxis in patients submitted to moderately emetogenic
      chemotherapy, where the prescribed chemotherapy was recorded. The aim of our
      study was to evaluate the incidence of undertreatment and to detect clinical and
      nonclinical factors able to explain its variability. METHODS: An observational
      study on the IGAR databank was performed to evaluate the incidence of
      undertreatment in the prescription in conditions of clinical trial, where the
      doses belonged to the eligibility criteria, and to analyze the importance of
      clinical and nonclinical factors using multifactorial logistic models. RESULTS:
      317 patients receiving cyclophosphamide, methotrexate, and fluorouracil (CMF) and
      224 anthracycline-based chemotherapy were considered. In the CMF-treated
      patients, 22.4% received full doses, whereas in 53.6% all three drugs of the
      schedule were down-dosed. In the anthracycline-treated group, 38.6% and 3.4% of
      patients submitted to chemotherapy containing epirubicin and doxorubicin,
      respectively, were undertreated. Logistic models showed that undertreatment in
      CMF-treated patients depended significantly on the geographic area and setting of
      chemotherapy administration. Although not significant, differences between age
      class and Karnofsky performance status were also detected. In the epirubicin
      treated group, all these factors were significant. CONCLUSIONS: The
      undertreatment of cancer patients is a relevant problem, because it could give,
      in daily clinical practice, worse results than those reported in clinical
      studies. Considering the setting of a clinical trial where our study was carried
      out, the incidence of undertreatment is surprisingly high. We do not know whether
      today, about 8 years after the IGAR study was carried out, the inappropriate dose
      of chemotherapy is still as frequent as we reported, but surely the topic
      deserves more attention.

PMID- 18338487
TI  - Epirubicin-vinorelbine intravenous combination followed by oral vinorelbine as
      first-line treatment in metastatic breast cancer.
AB  - Epirubicin and vinorelbine are considered active drugs in metastatic breast
      cancer. The optimal duration of a chemotherapy regimen for metastatic breast
      cancer patients is still unknown. Nevertheless, epirubicin has a dose-limiting
      cardiotoxicity. Vinorelbine is also available as oral formulation. In a
      multicenter phase II study, we analyzed the feasibility and the efficacy of a
      maximum of six cycles of i.v. epirubicin plus vinorelbine, followed by oral
      vinorelbine. We enrolled 30 patients with metastatic breast cancer. Each patient
      received epirubicin (75 mg/m2 on day 1) and vinorelbine (25 mg/m2 on days 1-8),
      every 3 weeks, for three cycles or six cycles in case of objective response or
      stable disease. When a clinical benefit was obtained, patients received oral
      vinorelbine (60 mg/m2 on days 1-8 every 3 weeks for three cycles). The regimen
      demonstrated to be active and well tolerated in metastatic breast cancer, and 6-8
      months represented the optimal treatment duration. Maintenance therapy with oral
      vinorelbine was feasible, effective, safe and well accepted by the patients.

PMID- 18338488
TI  - Survival benefit with GM-CSF use after high-dose chemotherapy in high-risk breast
      cancer.
AB  - AIMS AND BACKGROUND: The role of high-dose chemotherapy in breast cancer has not
      been fully defined. It has been concluded that new trials should focus on
      defining potential subgroups that are more likely to benefit from high-dose
      chemotherapy. We compared survival differences in patients receiving human
      granulocyte-colony stimulating factor (G-CSF) or granulocyte-monocyte colony
      stimulating factor (GM-CSF) after high-dose chemotherapy with stem cell support.
      METHODS: High-risk non-metastatic breast cancer patients (axillary lymph node
      involvement more than 8) aged 16 to 65 years and with a performance status < or =
      1 underwent high-dose chemotherapy with autograft. Written informed consent was
      obtained from every patient, and the study was approved by the local ethics
      committee. RESULTS: For 54 eligible women, the median follow-up was 41.4 months.
      The five-year disease-free survival was 45.7%. The five-year projected overall
      survival rate was 53.9%. Among them, patients who received GM-CSF (n = 12)
      posttransplant lived longer than the patients who received G-CSF (n = 15) (five
      year survival rates, 46.6% vs 75%, P < 0.050). The patients who received GM-CSF
      posttransplant had fewer relapses (5 vs 9). However, between the two groups there
      was no statistically significant difference regarding disease-free survival rates
      calculated with the Kaplan-Meier method (58.8% vs 40%; P = 0.121). CONCLUSIONS:
      Patients receiving GM-CSF posttransplant lived longer and they had fewer relapses
      than those who received G-CSF. This result merits consideration. The antitumor
      activity of GM-CSF should be investigated further in prospective randomized
      trials.

PMID- 18338489
TI  - An oxaliplatin + 5-fluorouracil bolus + folinic acid (BFOL) regimen as first-line
      treatment in metastatic colorectal cancer patients.
AB  - AIMS AND BACKGROUND: The purpose of the study was to evaluate the outcome of
      metastatic colorectal cancer patients treated, as first line, with 5-fluorouracil
      bolus/leucovorin + oxaliplatin, in terms of response, progression-free and
      overall survival. MATERIALS AND METHODS: A retrospective cohort of consecutive
      metastatic colorectal cancer patients, treated from 2003 to 2006, was identified
      and analyzed. All patients, without a central venous device, were treated with
      oxaliplatin + 5-fluorouracil and leucovorin. RESULTS: Twenty-five metastatic
      colorectal cancer patients were treated. No 3-4 grade toxicity was observed. Five
      of 23 patients achieved a partial response: one of them resulted in a complete
      response after radiofrequency and another one after surgery. Fifteen of 23
      patients had stable disease (one underwent radical surgery after chemotherapy,
      obtaining a complete remission) and 3 had progressive disease. Median progression
      free survival was 7.2 months, and median overall survival was 30 months.
      CONCLUSIONS: Based on this case-series study, the regimen seems to offer a good
      control of disease (86.9%) and can be considered as an alternative choice for
      patients who cannot receive continuous infusion.

PMID- 18338490
TI  - Negligible advantages and excess costs of routine addition of breast
      ultrasonography to mammography in dense breasts.
AB  - AIM: To assess the role of breast ultrasonography as a complement to negative
      mammography in radiologically dense breasts. MATERIAL AND METHODS: Out of a total
      series of 49,044 consecutive mammograms reported as negative in asymptomatic
      women, 25,665 (52.3%) were coded as dense (BI-RADS D3-4) and ultrasonography was
      recommended. Due to organizational problems, ultrasonography was performed
      immediately or within 1 month only in 5,227 cases, representing the study series.
      RESULTS: Two cancers were detected at immediate ultrasonography (0.03%). The
      cancer detection rate in women aged 40-49 and 50-69 years was 0.002% and 0.07%,
      respectively. The benign biopsy rate was 0.5% for core biopsies and 0.02% for
      surgical biopsies. The cost per ultrasonography-assessed woman was Euro 56.05,
      whereas the cost per additional mammographically occult but ultrasonography
      detected cancer was Euro 146,496.53. The mammograms of the 2 cancer cases
      underwent blind review by an expert reader and were confirmed as negative.
      DISCUSSION: Our findings show a low cancer detection rate, substantially lower
      compared to other clinical studies of ultrasonography in dense breasts, though in
      accordance with preliminary evidence from an Italian randomized clinical trial
      within a population-based screening program. The policy of adding ultrasonography
      to negative mammography in dense breasts seems to have very limited cost
      effectiveness, and should not be adopted in routine practice before results of
      ongoing clinical trials are available.

PMID- 18338491
TI  - Natural fluorescence spectroscopy of human blood plasma in the diagnosis of
      colorectal cancer: feasibility study and preliminary results.
AB  - AIM AND BACKGROUND: Fluorescence spectroscopy of biomolecules is considered a
      promising method to discriminate in vivo normal tissue from malignant tissue at
      various sites including breast, cervix, lung, and colon. However, only few
      studies have been reported on the feasibility of exploiting fluorescence
      spectroscopy of blood to characterize pathological changes usable in diagnostic
      oncology. In this study, the fluorescence characteristics of human blood plasma
      have been studied in the visible spectral range in an attempt to discriminate
      patients with colorectal cancer from subjects of a control population. PATIENTS
      AND METHODS: The study involved 341 subjects, including 169 blood donors with no
      evidence of disease, 143 patients bearing colorectal adenocarcinomas (36 in the
      colon, 38 in the sigmoid colon and 69 in the rectum), 11 patients with local
      relapse, 10 patients with familial adenomatous polyposis and 8 with single
      adenomas. Blood samples were collected from all subjects and plasma fluorescence
      spectrum was analyzed using a conventional spectrofluorometer. RESULTS: The
      intensity of a fluorescence emission peak around 615-635 nm, which could
      reasonably be ascribed to endogenous porphyrins, was significantly different
      between patients bearing colorectal cancer and blood donors. The diagnostic
      capacity of the method was tested by ROC analysis, which resulted in an area
      under the curve of 0.72, close to that reported for the CEA test. CONCLUSION:
      These results, although preliminary, suggest the potential of fluorescence
      measurements of blood plasma as an additional method for diagnostic application
      in colon cancer.

PMID- 18338492
TI  - Aberrant promoter methylation can be useful as a marker of recurrent disease in
      patients with cervical intraepithelial neoplasia grade III.
AB  - INTRODUCTION: Although studies of risk factor profiles have been conducted to
      identify biological markers to predict the natural history of cervical
      intraepithelial neoplasia (CIN) grade III, there is not sufficient information to
      support the routine clinical use of any biomarker. OBJECTIVES: The purpose of
      this study was to examine aberrant promoter methylation, which is implicated in
      cancer development and progression, in CIN III lesions in order to identify
      markers associated with more aggressive biological behavior that could be used to
      recognize women who are at higher risk of recurrence. PATIENTS AND METHODS: We
      used methylation-specific polymerase chain reaction to analyze promoter
      hypermethylation of 8 genes (p16, RARbeta, GSTP1, MGMT, p14, TIMP3, E-cad and
      DAPk) in 33 uterine cervix cones with CIN III that were also submitted to human
      papillomavirus (HPV) genotyping. All 33 patients in this study had been
      clinically followed after conization with Papanicolaou smears, colposcopy, and
      biopsy when indicated, every 6 months during 5 years. RESULTS: Of the 33
      patients, 12 (36%) underwent immediate hysterectomy after conization for having
      compromised cone margins, 14 (43%) have not relapsed, and 7 (21%) presented CIN
      relapse. The frequency of HPV infection in this group was 97% and no significant
      difference between the groups was observed. HPV of high oncogenic risk was
      present in 29 (87.9%) cases; HPV 16 was the most frequent (69.7%), while HPV 18
      was found in 33.3%; however, it was associated with HPV 16 in 15.1%. Concomitant
      infection by HPV 6/11 was detected in 21.2% (15.1% with HPV 16 and 6.1 with HPV
      18). 85.7% (6/7) of patients with recurrence had HPV 18 vs 0% (0/14) of patients
      without recurrence (P = 0.0001). At least 1 of the 8 genes was found
      hypermethylated in all samples. Concomitant hypermethylation of several genes was
      frequently found. However, CIN relapse was only seen in the cases with
      hypermethylation of 3 or more of the 8 genes studied (P = 0.0039). CONCLUSION: We
      suggest that aberrant promoter methylation may play a role and may serve as a
      useful biomarker in the recurrence of CIN.

PMID- 18338493
TI  - Factors affecting survival in breast cancer patients following bone metastasis.
AB  - AIMS AND BACKGROUND: The purpose of the study was to identify prognostic factors
      that affect survival following bone metastasis in breast cancer patients with
      first metastases in the skeletal system. METHODS AND STUDY DESIGN: We analyzed
      retrospectively the data of 248 metastatic breast cancer patients whose first
      distant metastasis was in the skeleton. RESULTS: The median age of the patients
      at diagnosis was 46 years (range, 23-76). Nearly half of the patients were
      premenopausal (52.4%). The median disease-free survival was 24 months. For most
      of the patients (221), bone was the sole first metastatic site, and the disease
      remained confined to the bone in 99 of them. The remaining patients (n = 27) had
      both bone and visceral metastasis at the time of first relapse. One hundred and
      fourteen of the patients (46%) had died by the time of analysis. With the median
      follow-up of 50.5 months from diagnosis, median survival after bone metastasis
      was 32 months. In univariate analyses, statistically significant predictors for
      survival after bone metastasis were axillary lymph node status, T stage of
      disease, hormone receptor status of the primary tumor, the presence of
      lymphovascular invasion, involvement of skin, the presence of additional
      nonosseous metastatic sites at the time of bone relapse, and disease-free
      interval. In multivariate analyses, the presence of additional non-osseous
      metastatic sites at the time of bone relapse, T stage of disease, hormone
      receptor status of the primary tumor, and the presence of lymphovascular invasion
      were found to be significant independent prognostic factors. CONCLUSIONS: In the
      result of study, for patients with breast cancer, survival following bone
      metastasis is affected by secondary prognostic factors such as disease-free
      interval and extent of metastasis besides primary prognostic factors related to
      the primary tumor.

PMID- 18338494
TI  - Appendectomy or right hemicolectomy in the treatment of appendiceal carcinoid
      tumors?
AB  - AIMS AND BACKGROUND: Carcinoids of the appendix continue to be of interest,
      despite their low incidence. There is still considerable controversy surrounding
      these tumors, especially with regard to the role of right hemicolectomy in the
      surgical management. The aim of this work was to explicate the current
      therapeutic knowledge and to review the criteria for the indications of
      appendectomy or hemicolectomy. METHODS: The records of patients who underwent
      appendectomies from 1990 to 2000 were analyzed. Seven patients were included in
      the study. The clinical data were reviewed for demographic details, tumor size,
      localization in the appendix, histological patterns and surgical procedures. All
      patients underwent appendectomy including removal of the mesenteriolum, and in
      one of them a right hemicolectomy was performed 3 weeks later. The mean follow-up
      was 7 years (range, 4-14). Follow-up data included symptoms, urinary 5
      hydroxyindoleacetic acid, ultrasound examination, computerized tomography, and
      octreotide scanning. RESULTS: Seven patients (0.9% of all appendectomies) were
      reported to have carcinoid tumors of the appendix. They were 3 men and 4 women
      with a mean age of 29 years. All patients were admitted for appendicitis. None
      suffered from the carcinoid syndrome. The site of the tumor was the apex of the
      appendix in 4 cases, the body in 2 cases and the base in 1 case. Mean tumor
      diameter was 8 mm (range, 5-29 mm); in 6 patients it was <2 cm. Treatment was
      appendectomy in all cases; additional right hemicolectomy was necessary in one
      case because of a tumor of more than 2 cm with invasion of the mesoappendix and
      lymph nodes. The 7-year survival rate is 100%. Six patients are without disease,
      while 1 patient (the one who underwent a right hemicolectomy) developed
      metastases in the liver 6 years after the operation. This patient, who was
      treated with a liver resection, is still alive. CONCLUSIONS: According to current
      guidelines, an appendectomy may be performed for small carcinoid tumors (<1 cm).
      Reasons for more extensive surgery than appendectomy are tumor size >2 cm,
      lymphatic invasion, lymph node involvement, spread to the mesoappendix, tumor
      positive resection margins, and cellular pleomorphism with a high mitotic index.
      The criteria that direct us towards major (hemicolectomy) or minor surgery
      (appendectomy) are controversial. Tumor size is still considered the most
      important prognostic factor, with a presumed increase in the risk of metastasis
      for tumors greater than 2.0 cm. The accepted treatment of such tumors is a right
      hemicolectomy. However, there is no evidence demonstrating a survival benefit for
      right hemicolectomy over simple appendectomy in patients with carcinoids greater
      than 2.0 cm in diameter.

PMID- 18338495
TI  - Negative impact of heat exposure on cosmesis after conservative treatment for
      breast cancer.
AB  - AIM AND BACKGROUND: To identify the factors influencing cosmesis after
      conservative treatment in breast cancer. METHODS: Retrospective analysis was done
      on 424 patients who underwent postoperative radiotherapy after conservative
      surgery for breast cancer from February 1992 to January 2002. Most of the
      patients underwent quadrantectomy. Whole breast irradiation up to 50.4 Gy was
      delivered in 28 fractions followed by a 10 Gy boost in 5 fractions to the tumor
      bed. Regional lymph node irradiation was administered if indicated. Breast
      cosmesis was scored in 4 tiers. Breast symmetry was analyzed by the relative
      distance from the sternal notch to the nipple, using photos taken prior to
      radiotherapy and 2 years after its completion. Median follow-up was 64 months.
      RESULTS: Breast cosmesis was excellent in 15%, good in 63%, fair in 19%, and poor
      in 3% of the patients. In multivariate analysis, tumors >2 cm (P = 0.0109), lower
      quadrant location (P = 0.0026), lymph node irradiation (P = 0.0028), and heat
      exposure (P = 0.0152) were related to poor cosmesis. The cosmesis score after
      radiotherapy compared to the pre-radiotherapy score was deteriorated in patients
      who had undergone lymph node irradiation (P < 0.0001) and heat exposure (P =
      0.0027). Breast symmetry was worse for patients who had tumors >2 cm (P <
      0.0001), upper quadrant tumor location (P < 0.0001), chemotherapy in combination
      with radiotherapy (P = 0.0136), lymph node irradiation (P = 0.0006) and heat
      exposure (P = 0.0355). Changes in symmetry by radiotherapy were greater for lymph
      node-irradiated patients (P < 0.0001). CONCLUSIONS: With larger tumor size, lymph
      node irradiation, and chemotherapy in combination with radiotherapy, heat
      exposure was found to have a negative impact on cosmesis in patients undergoing
      conservative treatment for breast cancer. Patients should therefore be advised to
      avoid heat exposure after breast irradiation.

PMID- 18338496
TI  - Importance of novel sequence alterations in the FHIT gene on formation of breast
      cancer.
AB  - AIMS AND BACKGROUND: The character, role and impact of FHIT gene alterations, for
      which recent studies have shown that the gene has a role in the early stage of
      carcinogenesis in breast cancer, are still unclear. Thus, the current study
      evaluated FHIT gene mutations from breast tissue of women with malignant and
      benign breast disease and to elucidate the frequency and type of mutations in
      this gene. PATIENTS AND METHODS: Mutations in exons 5-9 of the FHIT gene were
      screened using the intronic primer pairs in 83 breast (67 malignant and 16
      benign) tissue samples by single-strand conformational polymorphism and
      sequencing analysis. RESULTS: FHIT mutations were detected in 13 of the 67
      malignant cases (19.4%) and 2 of the 16 benign cases (12.5%). Four different
      sequence variants were determined: two novel frame shift mutations (codon 90
      insA, codon 146 delT), one intronic novel mutation (IVS8 -17 insA), and one
      previously identified silent transition type alteration (codon 88 C to T). In
      addition, determination of this silent alteration caused formation of new exonic
      splicing enhancer (ESE) motifs on mutated sequences by using the ESEfinder
      program. CONCLUSIONS: Our data contribute significantly to that currently known
      about the presence of FHIT gene mutations on the formation of breast cancer.

PMID- 18338497
TI  - Investigation of mutations and expression of the FHIT gene in Turkish patients
      with brain metastases derived from non-small cell lung cancer.
AB  - AIMS AND BACKGROUND: Brain metastases occur in 20-40% of patients with cancer,
      and their frequency has increased over time. Lung, breast and skin (melanoma) are
      the most common sources of brain metastases. Recent studies show that several
      genes such as CD44 and PTEN have roles in the suppression of metastatic growth.
      Although it has been determined that there is a relationship between the FHIT
      gene and several primary tumors, its role in the initiation and progression of
      brain tumors has not yet been entirely explained. Furthermore, it is not known
      whether the FHIT gene has a role in the formation of brain metastases. PATIENTS
      AND METHODS: The present study investigated mutations of the FHIT gene in Turkish
      patients with brain metastases derived from non-small cell lung cancer (NSCLC).
      Single-strand conformational polymorphism and sequencing analysis of the coding
      exons (5-9) of the FHIT gene were performed on 26 tissues. Furthermore, the level
      of Fhit protein expression of 36 tumor tissues was identified by
      immunohistochemistry. RESULTS: Using single-strand conformational polymorphism
      and sequencing analyses, no point mutations of the FHIT gene were detected in
      brain metastases derived from NSCLC. However, it was observed that Fhit protein
      expression was reduced in 88.9% of subjects. CONCLUSIONS: We suggest that the
      FHIT gene may be turned off in brain metastases via other genetic/epigenetic
      mechanisms rather than mutations.

PMID- 18338498
TI  - Neutropenic enterocolitis: is there a right timing for surgery? Assessment of a
      clinical case.
AB  - Neutropenic enterocolitis is a severe and potentially life-threatening
      complication that may affect patients undergoing chemotherapy for acute leukemia
      or lymphoma. These patients may develop systemic sepsis through bacterial or
      fungal translocation across the intestinal wall. In many cases neutropenic
      enterocolitis is confined to the cecum, but the entire colon is sometimes
      involved. Most patients are treated conservatively because an improvement occurs
      when the absolute neutrophil count rises. However, a surgical approach consisting
      of resection of the colon may sometimes be necessary, even in patients with
      complete aplasia and a high risk of complications. The right time to perform
      surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is
      an important prognostic factor which could act as a guide to surgical indication.
      We analyze a case of neutropenic enterocolitis which occurred in a patient with
      acute myeloid leukemia during chemotherapy and we suggest that, as well as
      intestinal wall thickness, hemodynamic worsening should be considered an
      indication for surgery.

PMID- 18338499
TI  - 18FDG-PET evaluation correlates better than CT with pathological response in a
      metastatic colon cancer patient treated with bevacizumab-based therapy.
AB  - Around 20-30% of patients with hepatic metastasis from colorectal cancer can
      undergo liver resection, but the increased response rate obtained with the
      addition of monoclonal antibodies to chemotherapy regimens could result in a
      higher rate of liver surgery. In this report we describe the case of a patient
      who underwent a liver resection after neoadjuvant treatment with capecitabine,
      oxaliplatin and bevacizumab and who achieved a complete pathological response of
      the liver metastasis. A preoperative CT scan demonstrated a partial response to
      the treatment while 18FDG-PET scan correctly evaluated the complete pathological
      response in the liver and detected an active interaortocaval lymph node
      metastasis. New specific studies are required to evaluate the imaging response in
      metastatic colorectal cancer patients especially after treatment with new,
      targeted agents.

PMID- 18338500
TI  - Silent colon carcinoma presenting as a hepatic abscess.
AB  - Penetration and abscess formation in an adjacent parenchymal organ as
      presentation of a colon cancer is very uncommon. We report a rare case of
      pyogenic liver abscess as the first manifestation of an infiltrative and
      penetrating hepatic flexure colon carcinoma without liver metastases. A 50-year
      old woman was admitted with right abdominal pain, fever and chills. The initial
      diagnosis was a pyogenic liver abscess. Subsequent CT scan and colonoscopy
      evidenced a hepatic flexure colon cancer abscessed within segment 6 of the liver.
      Eight months after a right colectomy and liver resection there was no evidence of
      disease. The occurrence of a pyogenic liver abscess should raise the suspicion of
      a silent colon cancer.

PMID- 18338501
TI  - Duodenal epithelioid angiosarcoma: immunohistochemical and clinical findings. A
      case report.
AB  - Angiosarcomas are uncommon malignant tumors of vascular endothelium that
      represent less than 1% of all sarcomas. The epithelioid variant of angiosarcomas
      is exceptionally rare, and the gastrointestinal tract is rarely involved.
      Angiosarcomas mainly involve skin and soft tissue and rarely occur in breast,
      liver, bone, and spleen. We present the case of a 30-year-old man who underwent
      an upper gastrointestinal endoscopy for melena. A duodenal reddish polypoid
      lesion was found, which on microscopic examination turned out to be an
      epithelioid angiosarcoma. The immunohistochemical features of the lesion
      supported this diagnosis. The patient died eight months after the diagnosis.
      Epithelioid angiosarcoma is an aggressive variant of angiosarcoma and must be
      considered in the differential diagnosis of gastrointestinal tumors.

PMID- 18338502
TI  - Primary pulmonary high grade non-Hodgkin's lymphoma in an elderly patient. A case
      report.
AB  - An 82-year-old non-smoker female was admitted with cough, fever and poor general
      health. Radiological examination revealed a right parahilar mass and a
      transbronchial biopsy confirmed the presence of a tumor. Immunohistochemical
      analysis established the diagnosis of high-grade primary pulmonary lymphoma. The
      rare nature of this disease, its non-specific clinical presentation and
      particular prognosis, also in elderly patients, are discussed in this article.

PMID- 18338503
TI  - Primary bilateral adrenal non-Hodgkin's Burkitt-like lymphoma: a rare cause of
      primary adrenal insufficiency. Case report and literature review.
AB  - AIMS AND BACKGROUND: Primary bilateral adrenal non-Hodgkin's lymphoma is an
      extremely rare entity. Only 44 cases have been reported in the literature. The
      most common presenting symptoms are abdominal pain, fever, asthenia,
      constipation, weight loss or typical symptoms of adrenal insufficiency,
      hypertension, darkening of skin, orthostatic hypotension or an addisonian crisis.
      METHODS: The case is presented of a 57-year-old man suffering from primary
      bilateral adrenal lymphoma with symptoms of adrenal insufficiency syndrome
      associated with bilateral, stabbing lumbar pain and a palpable mass on the left
      side. Laboratory tests revealed a considerable increase in lactate dehydrogenase
      levels, adrenal insufficiency, and high corticotropin levels. RESULTS: Abdominal
      CT scan showed two large adrenal masses. A CT-guided fine needle aspiration
      biopsy revealed a large B-cell non-Hodgkin's lymphoma. Combination chemotherapy
      according to the CHOP protocol with cyclophosphamide, doxorubicin, vincristine
      and prednisolone was initiated, which caused a slight reduction in size of the
      two adrenal masses. The patient underwent a bilateral adrenalectomy with almost
      complete excision of the tumors. Replacement therapy with cortisone acetate was
      initiated postoperatively. Adjuvant combination chemotherapy according to the
      CHOP protocol was started but renal failure gradually emerged and the treatment
      could not be completed. The patient died seven months after surgery due to acute
      bronchial pneumonia and progression of disease. CONCLUSIONS: Primary bilateral
      adrenal non-Hodgkin's lymphoma mainly affects adult men. Diagnosis is based on
      histological examination. Whether associated or not with radiotherapy,
      chemotherapy is the most recommended treatment. Surgery, where possible, seems to
      lead to an increase in survival rates, but it is not possible to draw any
      definite conclusions on its effectiveness as yet.

PMID- 18338504
TI  - Intratumoral hemorrhage of mammary phyllodes tumor after menstrual induction: a
      puzzling presentation.
AB  - BACKGROUND: Mammary phyllodes tumor is an uncommon stromal-epithelial neoplasm
      with a reported incidence of 0.3% to 0.5% of female breast tumors. Sudden, rapid
      growth of a mammary phyllodes tumor with intratumoral hemorrhage was noted in a
      45-year-old woman after menstrual induction with progesterone and norethindrone
      acetate. This case is presented here to highlight the possibility of such an
      onset of phyllodes tumor in order to facilitate its prompt diagnosis. CASE
      PRESENTATION: A 45-year-old woman suffered from missed periods for 2 months and
      received progesterone for menstrual induction. After treatment, rapid enlargement
      of her left breast was noted. Tracing the history of the patient, we found that
      she had already felt an about 3 cm painless lump in her left breast 5 months
      before this episode. Sonography of the left breast showed a large cystic lesion
      with some echogenic content and about 150 mL of old blood was obtained by
      aspiration. Surprisingly, follow-up breast sonography 3 weeks later revealed a
      large irregular solid mass and a small amount of peripheral cystic content with
      markedly increased vascularity. Surgery was suggested. A large encapsulated mass
      consisting of heterogeneous yellow soft tissue and a cystic component measuring
      10 x 8 cm was totally excised. Microscopically, the sections revealed branching
      and cystically dilated glands lined by cuboidal to columnar epithelial cells in a
      myxoid hypercellular fibroblastic stroma with hyperchromatic nuclei and frequent
      mitotic figures. The final histological diagnosis was malignant phyllodes tumor.
      CONCLUSION: Progesterone for menstrual induction may cause rapid growth of a
      phyllodes tumor with resultant internal hemorrhage. Only with the awareness of
      this entity can a prompt diagnosis be made and optimal treatment be given.

PMID- 18338505
TI  - A case of Stevens-Johnson syndrome possibly induced by amifostine during
      radiotherapy.
AB  - Skin reactions to amifostine are considered to be rare. Here we describe the case
      of a patient who developed a severe skin eruption (Stevens-Johnson syndrome)
      during radiotherapy probably due to amifostine. As in most of the patients
      described so far, the worst lesions were located in the skin areas previously
      treated with radiotherapy.

PMID- 18338506
TI  - Clinical report on external irradiation combined with californium-252 neutron
      intraluminal brachytherapy for cervical carcinoma treatment.
AB  - AIMS AND BACKGROUND: Neutron rays produce high linear energy transfer radiation,
      which has particular radiobiological characteristics. The aim of the study was to
      observe the curative effects and complications of external irradiation combined
      with californium-252 (252Cf) neutron intraluminal brachytherapy for treatment of
      cervical carcinoma. METHODS AND STUDY DESIGN: From December 2000 to December
      2004, 128 cases of cervical carcinoma staged IIA to IIIB were treated with 252Cf
      neutron intraluminal brachytherapy using 8-10 Gy-eq per fraction, once a week.
      The total dose at reference point A was 36-40 Gy-eq in 4 to 5 fractions. From the
      second day after 252Cf neutron intraluminal brachytherapy, the whole pelvic
      cavity was treated with 6 MV X-ray external irradiation, applying 2 Gy per
      fraction 4 times per week. After 20-24 Gy of external irradiation, the center of
      the whole pelvic field was blocked with a 4-cm-wide lead shield; the total dose
      of external irradiation was 44-50 Gy. RESULTS: The short-term curative effects
      were 95.3% complete remissions and 4.7% partial remissions. The 3-year and 5-year
      local control rates were 93.5% and 87.9%, respectively. The 3-year and 5-year
      survival rates were 87.5% and 70%, respectively. The rates of radiation
      complications were 4.7% for radiation cystitis, 7.8% for radiation proctitis,
      6.3% for vaginal contracture and adhesion, and 5.5% for protracted radiation
      proctitis. The results of univariate and multivariate analysis indicated that
      differentiation of tumor cells and lymphatic metastasis are the main factors
      related to the clinical prognosis of cervical carcinoma. CONCLUSIONS: A
      combination of external irradiation with 252Cf neutron intraluminal brachytherapy
      for treatment of cervical carcinoma can be well tolerated by patients. The rate
      of local tumor control is high and radiation complications are few.

PMID- 18338507
TI  - Intrathoracic malignant peripheral nerve sheath tumor with angiosarcoma in a
      child with NF1.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon in children and
      adolescents but occur more frequently in NF1 patients. Angiosarcomatous
      differentiation in MPNSTs is a rare entity with poor prognosis. We report on a 13
      year-old boy with intrathoracic angiosarcoma arising in MPNST associated with
      NF1.

PMID- 18338508
TI  - Design and architecture in oncology as supportive care for cancer patients.

PMID- 18338509
TI  - Metronomic chemotherapy in elderly patients: do risks exceed benefits in some
      patients?

PMID- 18338510
TI  - Lung injury related to taxane treatment in cancer patients.

PMID- 18338511
TI  - [Satellite Symposium AIOM, Palermo, 2007. Venous thromboembolism and cancer].

PMID- 18338512
TI  - [The choice of treatment in advanced gastric cancer].

PMID- 18338513
TI  - Ideology, politics, and health care reform.

PMID- 18338514
TI  - Ownership form and consumer welfare: evidence from the nursing home industry.
AB  - This paper compares the likely consumer benefits of higher quality with the
      potentially greater production costs that result from increased not-for-profit
      activity in a nursing home services market area. The comparison of consumer
      benefits and costs is made possible by observing empirically how an increased
      market penetration of not-for-profit facilities affects the use of private-pay
      nursing home care. Increased (decreased) use of nursing home care suggests that
      the consumer benefits associated with additional not-for-profit nursing homes are
      greater (less) than consumer costs. The empirical results indicate that, from a
      consumer's perspective, too few not-for-profit nursing homes may exist in the
      typical market area of the United States. The policy implication is that more
      quality of care per dollar might be obtained by attracting a greater percentage
      of not-for-profit nursing homes into many market areas.

PMID- 18338515
TI  - Insurers' competitive strategy and enrollment in newly offered preferred provider
      organizations (PPOs).
AB  - While early growth in preferred provider organizations (PPOs) coincided with
      growth of managed care generally, recent expansion has come primarily at the
      expense of other managed care plans. Little is known about the micro behavior
      underlying these trends. In 2005, University of Michigan employees were offered
      PPOs for the first time by vendors who also offered other plans. PPOs helped the
      offering vendors maintain or increase their total enrollment share. PPOs were
      most attractive to workers who previously had chosen less managed plans. Because
      PPOs drew few enrollees from health maintenance organizations (HMOs), there was
      little evidence of a backlash against managed care in the context of the
      University of Michigan employee group.

PMID- 18338516
TI  - Death spiral or euthanasia? The demise of generous group health insurance
      coverage.
AB  - Employers must determine the types of health care plans to offer and also set
      employee premiums for each plan provided. Depending on the structure of the
      employee share of premiums across different health insurance plans, the
      incentives to choose one plan over another are altered. If employees know
      premiums do not fully reflect the risk differences among workers, such pricing
      can give rise to a so-called "death spiral" due to adverse selection. This paper
      uses longitudinal information from a natural experiment in the management of
      health benefits for a large employer to explore the impact of moving from a fixed
      dollar contribution policy to a partially risk-adjusted employer contribution
      policy. Our results show that implementing a significant risk adjustment had no
      discernable effect on adverse selection against the most generous indemnity
      insurance policy. This stands in stark contrast to previous studies, which have
      tended to estimate large impacts attributed to selection when employers move to a
      fixed-dollar policy from one with some risk adjustment. Further analysis suggests
      that previous studies, which appeared to detect plans in the throes of a death
      spiral, may instead have been reflecting an inexorable movement away from a non
      preferred product, one that would have been inefficient for nearly all workers
      even in the absence of adverse selection.

PMID- 18338517
TI  - Premium increases in state health insurance programs: lessons from a case study
      of the Massachusetts Medicaid buy-in program.
AB  - In March 2003, Massachusetts increased the premiums it charges to most enrollees
      in its CommonHealth-Working (CH-W) program. This study evaluates the impact of
      the premium change on disenrollment using a comparison group methodology. The
      findings indicate that the premium change had only a small, but statistically
      significant impact on program exits. The CH-W experience differs from other state
      programs that saw substantial enrollment declines in response to new or increased
      premiums. This is likely due to factors that make CH-W different from other
      programs, key of which are administrative procedures intended to minimize
      disenrollment due to premium nonpayment.

PMID- 18338518
TI  - The accuracy of reported insurance status in the MEPS.
AB  - Estimates of the number of insured and uninsured Americans are watched by
      numerous policymakers and the public, yet studies find respondents do not report
      their insurance status perfectly. Using four sources of validation data,
      including surveys of employers and providers, this paper assesses the quality of
      respondents' reports of private insurance and uninsurance in the Medical
      Expenditure Panel Survey Household Component (MEPS-HC), a nationally
      representative household survey. Regression analysis is used to assess the extent
      to which factors are associated with disagreements in reported insurance status
      across sources.

PMID- 18338519
TI  - Health-based risk adjustment: improving the pharmacy-based cost group model by
      adding diagnostic cost groups.
AB  - Since 1991, risk-adjusted premium subsidies have existed in the Dutch social
      health insurance sector, which covered about two-thirds of the population until
      2006. In 2002, pharmacy-based cost groups (PCGs) were included in the demographic
      risk adjustment model, which improved the goodness-of-fit, as measured by the R2,
      to 11.5%. The model's R2 reached 22.8% in 2004, when inpatient diagnostic
      information was added in the form of diagnostic cost groups (DCGs). PCGs and DCGs
      appear to be complementary in their ability to predict future costs. PCGs
      particularly improve the R2 for outpatient expenses, whereas DCGs improve the R2
      for inpatient expenses. In 2006, this system of risk-adjusted premium subsidies
      was extended to cover the entire population.

PMID- 18338520
TI  - Effects of diagnosed dementia on Medicare and Medicaid program costs.
AB  - This study examines the impacts of physician-diagnosed Alzheimer's disease and
      related dementias (ADRD) on Medicare and Medicaid program costs in 1994 and 1999.
      An innovative method is employed to estimate program payments over the life cycle
      starting at age 65. Using data from the 1994 and 1999 National Long-Term Care
      Surveys, merged Medicare claims, and national program data for Medicaid, we find
      that the share of total Medicare and Medicaid payments attributable to diagnosed
      ADRD was 5.46% in 1999. Total annual program payments attributable to ADRD
      decreased between 1994 and 1999, in contrast to an increase implied by a cross
      sectional approach.

PMID- 18338521
TI  - How to collect from patients without scaring them away.

PMID- 18338522
TI  - Tail insurance: watch out for the gotcha!

PMID- 18338523
TI  - Why we welcome Hispanic patients.

PMID- 18338524
TI  - Patients love my broken Spanish.

PMID- 18338525
TI  - Who's afraid of the NPDB?

PMID- 18338526
TI  - Why I lost six months of sleep.

PMID- 18338527
TI  - How to prevent employee fraud.

PMID- 18338528
TI  - Hospitalists and PCPs: a delicate balance.

PMID- 18338529
TI  - Comparison of the electromyographic variables at different muscle lengths and
      contraction intensities.
AB  - Thirty-three (33) healthy volunteers (2.29 +/- 2.4 years) participated. Two
      active surface electrodes were placed on the rectus femoris muscle: one on the
      motor point (M) and the other on the thickest distal portion of the muscle (V).
      The volunteer was positioned on a Bonet table, with his/her trunk fixed, thigh at
      90 degrees and leg with 105 degrees and 45 degrees flexion. The signal was
      collected simultaneously in the 2 electrodes and in the load cell, during the
      extension of the leg at 50% or 100% of the maximum voluntary isometric
      contraction (MVIC) for 5 seconds, repeated 3 times, with an interval of 1 minute.
      The EMG signal was obtained through a data acquisition module (EMG1000 - Lynx) of
      16 bits (LYNX), with band- pass filter of 20-1.000 Hz and sampling frequency of
      2.000 Hz. RMS and mean frequency (MF) were assessed with Matlab software.
      Statistical analysis consisted of the Wilcoxon test and Student t test (p <
      0.05). At 50% of the MVIC, the RMS was greater in the shortened muscle than the
      lengthened one. Whereas at 100% there was an inversion, with the lengthened
      muscle presenting greater amplitude. The FM both at 50% and 100% MVIC was greater
      for the muscle in the shortened position. It was possible to conclude that
      changes in muscular length and in contraction intensity alter the
      electromyographic variables.

PMID- 18338530
TI  - The origin of the premotor potential recorded from the second lumbrical.
AB  - PURPOSE: When recording with a palm electrode, a premotor potential (PMP)
      precedes the compound muscle action potential evoked from the second lumbrical
      muscle following median nerve stimulation. The origin of the premotor potential
      has remained uncertain. The aim of this study was to determine whether the PMP-2L
      is a SNAP derived from antidromically activated digital sensory branches of the
      median nerve. METHODS: We recorded three active electrodes were placed over the
      second lumbrical muscle, the third lumbrical muscle, the fourth lumbrical muscle
      by multi-channel recordings. RESULTS: PMPs are recorded only over the median
      digital sensory branches after stimulating the median nerve, while they are
      recorded only over the ulnar branch after stimulating the ulnar nerve.
      CONCLUSIONS: We conclude that the origin of the PMP is a SNAP arising from
      antidromically activated digital sensory branches.

PMID- 18338531
TI  - The effects of the innervation zone and interelectrode distance on the patterns
      of responses for electromyographic amplitude and mean power frequency versus
      isometric torque for the vastus lateralis muscle.
AB  - The purpose of the present study was to examine the effects of the innervation
      zone (IZ) and differences in interelectrode distance (IED) on the patterns of
      responses and mean values for absolute and normalized electromyographic (EMG)
      amplitude and mean power frequency (MPF) versus isometric torque for the vastus
      lateralis. Ten men performed submaximal to maximal isometric muscle actions of
      the dominant leg extensors, and four separate bipolar surface EMG signals were
      detected from the vastus lateralis using a linear electrode array. Two electrode
      arrangements had IEDs of 10 and 30 mm and were located directly over the IZ. Two
      other electrode arrangements also had IEDs of 10 and 30 mm, but were distal to
      the IZ. The results indicated that in 50% of the cases, the IZ affected the
      patterns of responses for absolute and normalized EMG amplitude and MPF versus
      isometric torque. In 80% of the cases, however, there were no differences between
      the electrode arrangements with 10 and 30 mm IEDs for the absolute and normalized
      EMG amplitude and MPF versus isometric torque relationships. Both electrode
      placement over the IZ and differences in IED affected the mean values for
      absolute EMG amplitude, but not those for absolute EMG MPF In addition, there
      were no mean differences among the four electrode arrangements for normalized EMG
      amplitude and MPF values. Thus, these findings supported normalization, and
      indicated that it is useful for reducing the influences of the IZ and differences
      in IED on absolute EMG amplitude and MPF data.

PMID- 18338532
TI  - EEG-EMG coherence changes in postural tasks.
AB  - PURPOSE: Recent studies have investigated the possible function of synchronous
      oscillatory activity within the sensorimotor cortex of monkeys and humans that is
      thought to arise from synchronous discharge of large numbers of cortical neurons.
      There has been found clear task-dependent changes in 15-30 Hz oscillations. In
      leg muscles, coherence also occurs in the same frequency band during voluntary
      static contraction. Therefore we investigated changes in coherence in leg muscles
      during several postural tasks. METHODS: We examined the coherence between EEGs
      and soleus EMGs during voluntary contraction and in various postural tasks.
      RESULTS: There was a significant coherence during voluntary static contraction,
      but not during standing, forward bending, or standing on one foot; whereas, there
      was significant coherence during stamping the ground. CONCLUSION: These results
      suggest that the coherence at 15-30 Hz originates from the motor cortex during
      voluntary contraction, not when doing postural tasks. Coherence analysis
      indicates that during postural tasks the motor cortex would not produce the
      synchronous discharge of large numbers of cortical neurons or might not induce
      soleus EMG activity.

PMID- 18338533
TI  - Neurophysiological examination of the Modified Modified Ashworth Scale (MMAS) in
      patients with wrist flexor spasticity after stroke.
AB  - The Modified Modified Ashworth Scale (MMAS) is a clinical test for the
      measurement of spasticity. The aim of the present study was to examine the
      validity of the MMAS in patients with wrist flexor spasticity after stroke. 27
      adult patients (14 women and 13 men) with first ever stroke resulting in
      hemiplegia with a mean (SD, range) age of 57.9 (11.6, 37-75) were included in the
      study. The outcome measures were the MMAS for the clinical assessment of
      spasticity, the Hslope/Mslope (Hslp/Mslp), and the H(max)/M(max) ratio for the
      neurophysiological evaluation. The mean of the Hslp/Mslp and the H(max)/M(max)
      were higher in patients with worse MMAS grades but the differences were not
      statistically significant. There was a significant positive correlation between
      the MMAS scores and Hslp/Mslp ratio as the new index of alpha motoneurone
      excitability or traditional index of H(max)/M(max) ratio (r = 0.39, p = 0.04). It
      is concluded that the MMAS to be a valid measure of spasticity after stroke.

PMID- 18338534
TI  - Study on transient VEP-based brain-computer interface using non-direct gazed
      visual stimuli.
AB  - It is necessary for brain-computer interfaces (BCIs) to be non-offensive devices
      for daily use to improve the quality of life of users, especially for the motor
      disabled. Some BCIs which are based on steady-state visual evoked potentials
      (SSVEPs), however, are unpleasant because users have to gaze at high-speed
      blinking light as visual stimuli. Furthermore, these kinds of BCIs may not be
      used as universal devices because SSVEPs are not detectable by some users.
      Considering these facts, we propose a novel BCI using a non-direct gazing method
      based on transient VEPs. This interface uses a low-speed blinking lattice pattern
      as visual stimuli, and users gaze at other visual targets displayed on the right
      and the left sides of the stimuli. The gazing direction is determined by the
      waveform difference of transient VEPs detected when users gaze at either target.
      Compared with SSVEP-based BCIs, the proposed BCI is less annoying because it uses
      a low-speed blinking pattern as visual stimuli and users do not have to gaze at
      the stimuli directly. In addition, bipolar derivation could reduce unnecessary
      signals and the number of responses used for signal averaging to detect transient
      VEPs, which leads to shorter detection time of the VEPs providing this interface
      with acceptable speed as a BCI in terms of determining gazing direction.
      Experiments with 7 volunteer subjects showed more than an 85% accuracy rate in
      gaze direction judgments. The result suggests that the proposed BCI can be used
      as a substitute for SSVEP-based BCIs, especially for users in which SSVEPs are
      not detected.

PMID- 18338535
TI  - Immediate effects of a rucksack type orthosis on the elderly with decreased
      lumbar lordosis during standing and walking.
AB  - The spinal orthosis, the so-called rucksack type orthosis (RO), has been used to
      relieve low back pain and fatigue during prolonged standing and walking for the
      elderly with spinal deformities. However, little is known about the RO's
      kinematical effects. Twenty-three elderly (78.9 +/- 6.9 years old) participated
      in experiment 1, and 13 elderly (78.4 +/- 7.9 years old) in experiment 2. They
      had decreased lumbar lordosis or lumbar kyphosis. In experiment 1, using the
      "Spinal Mouse", which can measure spinal curvature, the effects of the RO on
      posture during standing were investigated. In experiment 2, using
      electromyography, the effects of the RO on muscle activity during standing and
      walking were clarified. Lumbar curvature and the trunk angle of inclination
      during standing improved significantly when the RO was used. Back extensor muscle
      activities (T9, L3, and L5) during standing and walking decreased significantly
      when the RO was used. There were no significant differences in the activities of
      the upper trapezius and vastus lateralis during standing and walking. The present
      study suggests that the elderly with lumbar deformities might be able to stand
      and walk more efficiently with the RO. The RO could prove to be valuable in
      preservation therapy for the elderly with decreased lumbar lordosis or lumbar
      kyphosis.

PMID- 18338536
TI  - [Surgical anatomy of the anterior mediastinum].
AB  - The mediastinum is located from the thoracic inlet to the diaphragm between the
      left and right pleural cavities and contains vital structures of the circulatory,
      respiratory, digestive, and nervous system. Over the years, since there are no
      fascial or anatomic planes, anatomists and radiologists have suggested various
      schemes for subdividing the mediastinum and several anatomical and radiological
      classifications of the mediastinum are reported in the literature. The most
      popular of these scheme divides medistinum, for purposes of description, into two
      parts: an upper portion, above the upper level of the pericardium, which is named
      the superior mediastinum; and a lower portion, below the upper level of the
      pericardium. For clinical purposes, the mediastinum may be subdivided into three
      major areas, i.e. anterior, middle, and posterior compartments. The anterior
      mediastinum is defined as the region posterior to the sternum and anterior to the
      heart and brachiocephalic vessels. It extends from the thoracic inlet to the
      diaphragm and contains the thymus gland, fat, and lymph nodes. This article will
      review surgical anatomy of the anterior mediastinum and will focus on the
      surgical approch to anterior mediastinum and thymic diseases.

PMID- 18338537
TI  - [Thymectomy in myasthenia gravis: video-assisted procedures].
AB  - OBJECTIVE: We describe the technique, the benefits and the drawbacks of an
      original video-assisted thymectomy (VAT), performed through an inframammary
      cosmetic incision and median sternotomy in myasthenia gravis (MG) patients. This
      procedure is clinically valuable and cosmetically satisfactory so as to be very
      well accepted by patients, especially by young women. Minimal-access thymectomy
      has become increasingly popular as surgical treatment for patients with
      nonthymomatous myasthenia gravis because of its comparable efficacy, safety, and
      lesser degree of tissue trauma with conventional open surgery. METHODS: We report
      a review/interview of 180 MG patients treated between 1993 and 2005. According to
      Myasthenia Gravis Foundation of America (MGFA), complete stable remission (CSR)
      and pharmacologic remission (PR) were calculated at the end of a minimal period
      of 12 months. RESULTS: A clinical remission was obtained in 41.1% (CR 27.8%, PR
      13.3%), who had been followed for at least 12 months from surgery. 95% of these
      patients judged their cosmetic results to be excellent or good. CONCLUSIONS:
      Thymectomy in MG video-assisted infra-mammary cosmetic incision has shown to be a
      useful surgical approach as demonstrated by the good functional and very good
      aesthetic results, associated with a very low morbidity and no mortality.

PMID- 18338538
TI  - Perioperative evaluation of myasthenia gravis.
AB  - Myasthenia gravis (MG) is the prototype of antibody mediated autoimmune disease
      and results from the production of autoantibodies against the acetylcholine
      receptor (AChR) of the neuromuscular synapse. Adequate preoperative evaluation of
      the myasthenic patient must be carried out carefully. Age, sex, onset and
      duration of the disease as well as the presence of thymoma may determine the
      response to thymectomy. Specific attention should be paid to voluntary and
      respiratory muscle strength. The preoperative preparation of MG patients is
      essential for the success of surgery. It depends on the severity of clinical
      status and changes if myasthenic patients receive anticholinesterase therapy.
      Myasthenic patients may have little respiratory reserve, and hence depressant
      drugs for preoperative premedication should be used with caution and avoided in
      patients with bulbar symptoms. The anaesthetic management of myasthenic patient
      must be individualized in according to the severity of the disease and the type
      of surgery required. The use of regional or local anaesthesia seems warranted
      whenever possible. General anaesthesia can be performed safely when patient is
      optimally prepared and neuromuscular transmission is adequately monitored during
      and after surgery. Adequate postoperative pain control, pulmonary toilet, and
      avoidance of drugs that interfere with neuromuscular transmission will facilitate
      tracheal extubation. Myasthenia gravis is a disease with many implications for
      the safe administration of anaesthesia. The potential for respiratory compromise
      in these patients requires the anaesthesiologist to be familiar with the
      underlying disease state, as well as the interaction of anaesthetic and non
      anaesthetic drugs with MG.

PMID- 18338539
TI  - Perioperative management of thymectomy.
AB  - Thymoma is the most frequent type of tumor in the anterior-superior mediastinum.
      The presentation of thymomas is variable; most are asymptomatic and others
      present themselves with local compression syndrome or parathymic syndrome; rarely
      thymomas appear as an acute emergency. Surgery is the treatment of choice for
      thymic tumors and complete resection is the most important prognostic factor.
      Surgery with adjuvant radiation is recommended for invasive thymoma. The
      anaesthetic management of patients with mediastinal thymoma undergoing thymectomy
      is associated with several risks related to potential airway obstruction, hypoxia
      and cardiovascular collapse. Patients at high risk of perioperative complications
      can be identified by the presence of cardiopulmonary signs and symptoms. However,
      asymptomatic thymomas have been occurred with acute cardiorespiratory
      complications under general anaesthesia. A careful preoperative evaluation of
      signs, symptoms, chest X-ray, CT scan, MRI, cardiac echogram and venous angiogram
      should be helpful to investigate neoplasm presence and the area of invasion;
      moreover, an adequate airway and cardiovascular management, such as performing an
      awake intubation in the sitting position, allowing spontaneous and non-controlled
      ventilation, a rigid bronchoscope available and a standby cardiopulmonary bypass,
      is suggested to prevent the main life-threatening cardiorespiratory
      complications.

PMID- 18338540
TI  - The role of nuclear medicine in the management of thymomas.
AB  - AIM OF THE STUDY: To evaluate the role of nuclear medicine techniques in the
      management of patients with thymoma. MATERIALS AND METHODS: The Authors performed
      a review of the literature about the usefulness of traditional nuclear medicine
      and positron emission tomography in patients with thymic tumours. RESULTS AND
      DISCUSSION: Nuclear medicine imaging can provide additional information in cases
      of thymoma such as in differential diagnosis between thymic tumours, staging and
      restaging. Thallium-201 (201Tl), 99mTc-sestamibi and 99mTc-tetrofosmin are useful
      tumour-imaging agent. Another radiopharmaceutical useful in the management of
      thymomas is 111In-pentetreotide, a somatostatin analogue, used to define the
      receptor status and the extent of disease in malignant thymomas. Positron
      emission tomography (PET) is a powerful diagnostic tool for diagnosis, staging
      and restaging of neoplasms in general. The most used PET radiopharmaceutical is
      the fluorodeoxyglucose (18F-FDG), a glucose analogue. The uptake of FDG reflects
      the metabolic activity of organs and neoplasms and correlates with the tumour
      growth rate. There is a paucity of literature on the use of PET scanning in the
      diagnosis of thymoma. Further perspective studies with a larger number of cases,
      considering the development of hybrid imaging PET-CT and new PET
      radiopharmaceuticals, may increase the role of nuclear medicine in the diagnostic
      and therapeutic management of thymic neoplasms.

PMID- 18338541
TI  - Recurrence of thymoma: re-operation and outcome.
AB  - INTRODUCTION: The treatment of recurrent thymomas remains still controversial.
      PATIENTS AND METHODS: From 1972 to 2006, 265 (114 males and 118 females )
      patients with thymoma underwent surgery at Catholic University of Sacred Heart.
      Twenty of these 265 patients developed a recurrence of the initial thymoma, and
      they represent the population of the present study. RESULTS: One patient died of
      sudden death related to respiratory failure. The overall morbidity rate was 33%
      and the morbidity rate among myasthenic patients was 60%. 10 patients died during
      the follow-up; 2 of unrelated diseases, 2 of myasthenia gravis, and 6 of tumor
      growth. The overall actuarial survival rates were 43% and 37% at 5 and 10 years,
      respectively. Recurrences never appeared in patients with I stage of Masaoka and
      in type A and AB. CONCLUSIONS: Considering the particular spread of thymoma and
      the encouraging results of the aggressive surgical approach, re-resection should
      be recommended in respectable recurrent thymomas.

PMID- 18338542
TI  - Role of chemotherapy in malignant thymoma.
AB  - Thymomas and thymic carcinomas, which are rare epithelial tumors arising from the
      thymus gland, are the most common tumors of the anterior mediastinum. Surgery is
      the principal treatment and is curative in early stage disease. Radiation
      therapy, either alone or in combination with chemotherapy, may be an option both
      in not completely and completely resected disease. Chemotherapy is offered to
      patients with locally advanced or metastatic thymoma and induces excellent
      responses race and prolonged survival.

PMID- 18338543
TI  - [Effects of the thymectomy in a rehabilitation program and in quality of life in
      patients with myasthenia gravis].
AB  - OBJECTIVE: The purpose of this study is to estimate the effects of a
      rehabilitation program on patients with myasthenia gravis (MG) subordinates to
      thymectomy. MATERIALS AND METHODS: Patients were evaluated at baseline (T1) and
      at the end of the pulmonary rehabilitation. (T2), by undergoing spirometric
      measurements, 6-Minutes Walking Test (6MWT), Berg Balance Scales (BBS), Rivermead
      Mobility Index (RMI) and Short 36 Form Health Survey version 2 (SF-36v2). The
      rehabilitation program included exercise to improve the respiratory
      functionality, the cardiovascular fitness and the global posture. OUTCOME: A
      single patient obtained improvement pulmonary function, unmodified in the others
      two patients. Mobility and balance, estimated by the RMI and BBS, effort
      tolerance, estimated by the 6-MWT QOL, estimated by means of SF36v2 improved, and
      dyspnoea (Borg scale) reduction was obtained in all of the patients. DISCUSSION:
      A specific rehabilitative protocol does not exist for the patients with MG
      subordinates to thymectomy. The AA. conclude that the training relieves dyspnoea,
      increases the capacity to walk, and improves health-related quality of life.
      CONCLUSION: Future studies will define the role of the rehabilitation for, these
      patients and will optimize the protocol.

PMID- 18338544
TI  - [Esophageal atresia. Personal experience and review of the literature].
AB  - INTRODUCTION: A long gap between the esophageal pouches in esophageal atresia is
      a relatively rare finding; it adds a significant challenge in the surgical
      correction and final outcome. MATERIAL AND METHODS: We retrospectively reviewed
      all cases of long gap esophageal atresia managed at our institution between 2000
      and 2006, focusing on antenatal period, delivery weight, maurity, associated
      malformations, initial management and definitive repair. RESULTS: Sixteen
      patients with esophageal atresia were observed. Five of them (31%) presented a
      long gap. Delayed reconstruction was achieved in 4 children at an average age of
      63 days (range 40-95 days). Primary repair was possible at birth in one case. All
      children had a direct anastomosis with one or more Livaditis myotomies in four
      cases. DISCUSSION: Surgical management of long gap esophageal atresia remains
      controversial. Most authors believe that elongation of the native esophagus
      provides a better functional outcome. In particular conditions, when this goal
      cannot be achieved, esophageal substitution is the last resort. Many techniques
      have been proposed to obtain esophageal elongation; although all the procedures
      give acceptable results, none of them has been unanimously accepted by pediatric
      surgeons. The circular or spiral myotomy is still the most commonly used
      technique to lengthen the esophagus in the repair of long gap atresias.
      CONCLUSIONS: In our limited experience circular myotomy (single or double) has
      proven an effective and reliable technique which allows direct repair of the
      esophagus even in the presence of initial gaps of 4 vertebral bodies.

PMID- 18338545
TI  - [Malignant pleural effusion].
AB  - Malignant pleural effusion is a frequent condition with important prognostic
      repercussions on duration and quality of life. The neoplasms that more frequently
      determine pleural effusion are lung and breast cancer and pleural mesothelioma.
      Lymphomas, tumours of the genitourinary tract and gastrointestinal tract as a
      group account for a further 25%. Surgical treatment has palliative purposes and
      finalized to reduction symptoms and to improve quality of life. More frequent
      clinical presentation is a massive pleural efusion associated to dyspnoea and
      cough. Pleural aspiration is the first choice treatment but the recurrence rate
      equals to 100% within 1 month. Repeated pleural aspirations are indicated in
      those patients that have lower expectation of life. The recurrence risk can be
      reduced with chemical pleurodesis that allows the adhesion between pleural
      surfaces. Pleurodesis can be realized by the instillation of several substances
      by the tube of drainage (slurry) or during thoracoscopy (poudrage). Video
      Assisted Thoracoscopy (VATS) is a safe and well tolerated technique, a
      complication rate is lower than 0.5%, VATS can be used to obtain diagnosis and to
      treat patients with malignant pleural effusion and better expectation of life.

PMID- 18338546
TI  - Malignant pleural mesothelioma: utility of 18 F-FDG PET.
AB  - Malignant Pleural Mesothelioma is a rare tumour that arise from the mesothelial
      cells of the pleura and in recent time the incidence of this disease is rising.
      Because of the implications for management and therapy, it is important to assess
      the accurate staging. 18F-fluorodeoxiglucose Positron Emission Tomography (18F
      FDG PET) is become a useful tool in the diagnosis of many neoplasms, such as
      Malignant Pleural Mesothelioma. In particular it has been shown to be useful in
      the evaluation of the extent of pleural disease, in the establishment of lymph
      node involvement, in the evaluation of tumour invasion into the lung and thoracic
      wall, in the diagnosis of extrathoracic metastases, in the assessment of the
      response to treatment, and in planning radiotherapy. Developments in system
      technology, like improvements in hybrid system (integrated Positron Emission
      Tomography/Computed Tomography) and the discovery of new radiopharmaceuticals,
      promise to make PET much more useful and versatile in the future.

PMID- 18338547
TI  - [Evaluation of the rehabilitation program in a patient submitted to
      pleuropneumonectomy for malignant pleural mesothelioma].
AB  - OBJECTIVE: The purpose of this study is to test a rehabilitation program for the
      patients with malignant pleural mesothelioma (MPM) subordinates to
      pleuropneumonectomy. MATERIALS AND METHODS: A single patient was evaluated at
      baseline (TI) and at the end of the pulmonary rehabilitation (T2), by undergoing
      spirometric measurements, emogasanalisys and 6-Minute Walking Test (6-MWT).
      Outcome evaluation were administered with Visual Analogic Scales (VAS), Hospital
      Anxiety and Depression Scales (HADS) and Short 36 Form Health Survey version 2
      (SF-36). The rehabilitative program included exercise to improve the respiratory
      functionality, the cardiovascular fitness and the global posture. OUTCOME:
      Pulmonary function, effort tolerance, estimated by the 6-Minute Walking Test,
      quality of life, estimated by means of SF-36 v2 improved, and pain, estimated by
      Visual Analogic Scales, anxiety and depression estimated by Hospital Anxiety and
      Depression Scales reduction was obtained. DISCUSSION: Actually does not exist a
      specific rehabilitation protocol for MPM patients. We report that our protocol
      relieved dyspnoea, increased the capacity to walk, and improved health-related
      quality of life. CONCLUSIONS: Future studies will define the role of the
      rehabilitation for MPM patients and will optimize the protocol.

PMID- 18338548
TI  - Medico-legal aspects of mesothelioma.
AB  - The Authors, reviewing the Literature on asbestos-related Malignant Mesothelioma
      (MM), found that because of its very peculiar characteristics, the causal link
      between professional asbestos exposure and the development of this tumour is very
      difficult to define in respect to: diagnosis, causal link and individuation of
      possible culpable conducts. The evaluation of causal link in different medico
      legal areas is studied by different criteria. In civil law the criterion of weak
      causality is followed to allow compensation for damages. For institutional
      purposes in INAIL, the definition of causal link is particularly facilitated by
      the legal presumption of origin. In fact it is sufficient, that asbestos-related
      lesions are ascertained in individuals who are or were exposed at any time of
      their professional life to the risk of inhaling asbestos fibres. In criminal law,
      the current approach of the Supreme Court is to demand evidence of strong
      causality, with a high logical probability and rational credibility, and beyond
      reasonable doubt, because criminal liability is personal as established in
      article 27 of the Italian Constitution. It is worth pointing out that all the
      levels of evidence indicated above must pass the test of scientific suitability
      or possibility.

PMID- 18338549
TI  - Thyroidectomy for Graves' hyperthyroidism. Retrospective study of patients'
      appreciation.
AB  - AIM OF THE STUDY: To retrospectively investigate the patients' views of surgical
      treatment of Graves' hyperthyroidism. METHODS: One hundred two patients were
      included in the study and submitted to extensive subtotal thyroidectomy or total
      thyroidectomy between 1993-2003. Data were acquired from the responses to a
      questionnaire, that was completed by 83 patients. RESULTS: Before the operation
      the working/studying ability and the social/emotional relations were impaired in
      20% and 22% of cases. Preoperative information was adequate for 84% of patients.
      The perception of the hospital efficiency was favourable in 89% of cases, and the
      interpersonal relations with clinicians and nurses were very positive for 96% of
      patients. After the operation, all patients were hypothyroid on levothyroxine (l
      T4); unexpected problems with l-T4 therapy occurred in 6% of cases. Voice changes
      or neck discomfort were reported by 29% and 8% of patients. The aesthetic
      appearance of the scar was very satisfactory for 70% of patients, but 11% were
      unsatisfied. The working/studying ability and the social/emotional relations
      improved in 63% and 59% of cases. Eye symptoms improved in 71% of the patients
      with endocrine ophthalmopathy, but got worse in 60%. The quality of life,
      expressed with a 0 to 10 scale, improved from a mean preoperative score of 4.7 to
      a mean score of 7.9 (P = 0.000). Only 5% of patients expressed hesitation to
      recommend surgery to a friend with similar disease. CONCLUSIONS: Surgery is an
      effective therapy for selected cases of Graves' disease and meets the
      expectations of the majority of patients. Nevertheless some possible factors for
      dissatisfaction are pointed out.

PMID- 18338550
TI  - [The sentinel lymph node biopsy. Evolution and convalidation of the technique].
AB  - BACKGROUND: Sentinel node biopsy is a minimally invasive technique alternative to
      routine axillary dissection in breast cancer staging. This technique selects
      women with positive nodes who may benefit from axillary dissection, avoiding
      unnecessary operations in negative node biopsies. AIMS: In this article we report
      a 5 year multi disciplinary experience in sentinel node biopsy involving the
      General Surgery Unit of Imola Hospital in collaboration with Radiologist,
      Pathologists and Specialists in Nuclear Medicine. METHODS: From 2000 to 2004 the
      Authors treated 209 women performing 214 sentinel node biopsies (in 5 cases the
      tumor was bilateral). Sentinel node identification was undertaken by
      lymphoscintigraphy; in 15 cases we associated intradermal injection of blue dye.
      Lymph nodes were examined by at least 60 hematoxylin and eosin stained sections
      and when nodes found negative were further studied with immunohistochemical
      stains for cytokeratins. RESULTS: Sentinel node identification rate was 99.1%. In
      62 patients sentinel node was metastatic and in 17 such nodes micrometastases
      were detected. In 6 cases with single metastatic cells, axillary dissection was
      not perfomed, in accordance to current opinions. In 50 of 62 women with
      metastatic axillary nodes (80.6%) the sentinel node was the only metastatic one.
      Number of axillary dissections decreased of more than 70% in four years, from
      theoretical 214 to 62. CONCLUSION: Sentinel node biopsy is currently a validated
      technique and many breast cancer patients are spared a regional lymph node
      dissection without compromising local control and the accuracy of staging.

PMID- 18338551
TI  - [The Mirizzi syndrome. Analysis of an unknown complication of the gallstones].
AB  - BACKGROUND: Mirizzi syndrome is one possible complication of the gallstones. The
      incidence in patients treated with cholecystectomy is 0.7-1.1%. MATERIALS AND
      METHODS: We have analyzed on 4123 colecistectomie conduct in Unit of General
      Surgery and Organ Transplantation of the University of Parma from January 1992 to
      October 2006, 46 cases of syndrome of Mirizzi (1.1%) with age comprised between
      29-82 years (medium 67.8 years) were 28 women (60.9%) and 18 men (39.1%). We have
      considered the symptomatology, the diagnostic and therapeutic way, the
      comorbidity. RESULTS: In 19 cases (41.3%) there were the signs of acute
      cholecystitis; in 28 cases (60.9%) the clinical picture was characterized from
      repeated biliary pain. The jaundice was present in 29 cases (63%) with
      hyperpyrexia (>38 degrees) in 27 cases (58.7%). In 14 cases (30.4%) was a Mirizzi
      type I, in 32 cases (69.6%) a Mirizzi of type II. CONCLUSIONS: The Mirizzi
      syndrome is a diagnosis frequently conduct intraoperatively. The surgical therapy
      is characterized by the acknowledgment of the biliary structures, the complete
      removal of the stones, the surgical therapy of the leaks.

PMID- 18338552
TI  - [Endovascular treatment of traumatic lesions of thoracic aorta. Our experience].
AB  - OBJECTIVES: To report our experience with endovascular repair of descending
      thoracic aorta in patients with acute and chronic traumatic lesions due to blunt
      chest trauma in last 4 years. MATERIAL AND METHODS: From January 2002 to
      September 2006, 5 patients underwent endovascular repair of descending thoracic
      aorta for acute (3 cases) and chronic (2 cases) traumatic lesions due to road
      traffic accidents (motorcycle crash: 1; car crash: 4). RESULTS: Stent-graft
      placement was successful in all cases with good early outcomes and without late
      complications (follow up 3-48 months). CONCLUSION: Endovascular repair of
      descending thoracic aorta lesions, due to blunt chest trauma, is a feasible and
      valid alternative to conventional open operation.

PMID- 18338553
TI  - [Personal experience using radioimmunoguided surgery (RIGS)].
AB  - Radio Immuno Guided Surgery (RIGS) is a technique that has numerous uses in
      oncology. It is characterised by a multidisciplinary approach by nuclear
      physician and surgeon for diagnosis and treatment; it uses colloid radiotracers,
      monoclonal antibodies or non-immunological tracers. We adopted this technique in
      281 patients: 256 (91.9%) (range 26-82) with breast disease (breast cancer or
      occult breast lesions) and 25 (8.9%) (range 42-84) with colorectal cancer
      localized or recurrent. We used monoclonal antibodies (ArcitumoMab 99mTc
      labelled) for colorectal carcinomas and aggregates of human serum albumin 99mTc
      labelled for Radioguided Occult Lesion Localization (ROLL) and Sentinel Lymph
      Node Biopsy (SLNB). All patients were studied preoperatively by routine blood
      tests, instrumental exams and tumoral markers. Amongst patients with breast
      disease, 142 breast cancers and 114 occult breast lesions were found. Among
      patients with colorectal disease, 8 cases had localized colorectal cancer and 17
      cases had locoregional recurrence and/or metastasis. In all cases pathologic
      sites were detected by probe during surgery. The RIGS is indicated for ROLL and
      SLNB; nevertheless it is also suggested for pre- and intraoperatively staging of
      primary and recurrent colorectal cancers. This method gives a chance for a
      radical surgical and oncologic treatment in localized and recurrent cancer.
      Prospective studies are needed in order to estimate survival and usefulness of
      this methodology.

PMID- 18338554
TI  - Duodenal Crohn's disease.
AB  - The Authors report on an uncommon case of duodenal Crohn's disease in an adult
      man. The patient was admitted for a history of epigastric pain, recurrent
      vomiting, weight loss and low grade fever. He was evaluated with
      esophagogastroduodenoscopy and with radiological double-contrast technique. Then,
      due to these untreatable clinical manifestations, he underwents a surgical
      treatment.

PMID- 18338555
TI  - Giant liposarcoma of the mesentery. Report of a case.
AB  - Liposarcomas represent the single most common type of soft tissue sarcoma. Its
      abdominal localization is rare, occurring in only 5% of cases. A 55 year old male
      was found to have a case of primary giant liposarcoma of the mesenterium with a
      maximum diameter of 40 cm and weight of 9 kg. Computed tomography revealed the
      presence of a large mass presenting a dishomogeneous density with an adipose
      component, probably of mesenteric origin. A xifopubic laparotomy confirmed the
      presence of a pedunculated growth originating from the mesentery. The mass was
      removed and the histopathological report noted a well differentiated sclerosing
      liposarcoma with the peritoneal liquid positive for malignant cells. Surgery
      currently represents the only possibly curative therapy for this type of tumour
      but close long-term follow up and accurate evaluation of the clinicopathologic
      parameters are needed.

PMID- 18338556
TI  - Rectus sheath haematoma. report of two cases.
AB  - Rectus sheath haematoma is a well-documented clinical entity. The accumulation of
      blood within the rectus sheath produces a painful swelling that can mimic an
      intraperitoneal mass, with features of an acute abdomen. Accurate diagnosis is
      essential, in order to avoid an unnecessary laparotomy. Two cases of this entity
      are reported. The correct diagnosis was established by appropriate assessment of
      the clinical, laboratory and imaging findings.

PMID- 18338557
TI  - [Urachus' carcinoma: a case report].
AB  - Urachus' carcinoma represents a rare oncologic disease with an unfavourable
      prognosis due to the usual delay of correct diagnosis for its anatomical
      localization. Its surgical treatment varies from radical cystectomy to segmentary
      resection of the bladder with pelvic lymphadenectomy. We report a case occurred
      in a ninety years old female, in which the diagnosis was achieved only at
      laparotomy. The patient was submitted to surgery with the only generic diagnosis
      of "lower abdominal mass", and treated with segmentary resection.

PMID- 18338558
TI  - [Petrarca and medicine (in the 7th centennial of Francesco Petrarca's birth].

PMID- 18338559
TI  - [Performance-intensity function of mandarin monosyllable and sentence materials
      for normal-hearing subjects].
AB  - OBJECTIVE: To analyze the monosyllabic and sentence lists of Mandarin speech test
      materials (MSTMs) which have been evaluated the equivalence of difficulty, and to
      establish the performance-intensity function (P-I function) for people with
      normal hearing. METHOD: Forty subjects (the age-ranged from 18 to 25 years old)
      who speak Mandarin well in their daily lives with normal hearing participated in
      this study. Eight of them joined the pilot study, which aimed to identify an
      appropriate presentation level for the formal test. Thirty-two subjects
      participated in the formal speech perception test. The results were analyzed by
      Statistical Package for the Social Sciences (SPSS) software version 11.0. Seven
      monosyllabic lists (50 words per list) and 15 sentence lists (50 key words per
      list) were used. RESULT: The results showed P-I function of 3.1% per dB for
      monosyllabic Mandarin materials and 7.4% per dB for sentence Mandarin materials.
      The sound pressure level of speech corresponding to a 50% recognition score for
      monosyllabic lists was 30.1 dBSPL or 10.1 dBHL, and 23.1 dBSPL or 3.1 dBHL for
      sentence lists. CONCLUSION: The study established the P-I function of the
      Mandarin monosyllabic and sentence materials with equal difficulty, which
      provides the normative data for identifying the normal hearing in a clinical
      setting.

PMID- 18338560
TI  - [Effect of stimulus intensity on auditory event-related potentials evoked by tone
      and speech].
AB  - OBJECTIVE: To explore the effect of stimulus intensity on auditory event-related
      potentials (AERP) evoked by tone stimuli and speech stimuli respectively. METHOD:
      Normal young participants were tested by both tone and speech stimulus with
      different intensity levels. Range of the intensity for the typical AERP to tone
      stimuli and speech stimuli were compared. Whether the effect of intensity
      on,speech stimuli AERP test is the same as that of the tone stimuli were
      analyzed. RESULT: When intensity level ranged from 40 dBSL to 70 dBSL, typical
      AERP were recorded more easily with speech stimuli than with tone stimuli (P <
      0.01). When stimulated by speech stimuli or by tone stimuli, the latency of P300
      decreased with higher intensity, the influences of intensity to P300 latency have
      significant difference (P < 0.01), but not to P300 peak amplitude. CONCLUSION:
      The effect of stimulus intensity on AERP evoked by speech stimuli is the same to
      the tone stimuli, but intensity range for typical AERP of speech stimuli was
      wider than tone stimuli. It may be resulted from that information contained in
      speech stimulus is more abundant than that contained in tone stimulus, or
      subjects were more familiar with speech stimulus than tone stimulus.

PMID- 18338561
TI  - [Relationship between fibrinogen level and pathogenesis of sudden sensorineural
      hearing loss].
AB  - OBJECTIVE: To study the relationship between fibrinogen level and pathogenesis of
      sudden sensorineural hearing loss(SSHI.). METHOD: Fifty patients (55 ears) with
      SSHL within 7 days of the onset were studied: a control group was consist of 50
      normal-hearing people who were individually matched on a pairwise basis according
      to the same gender and age. Both the patients and the normal people were tested
      for the parameters of hemorheology, blood biochemistry, whole blood cell count
      and clotting function. RESULT: Fibrinogen level and plasma viscosity in patients
      with SSHL were significantly higher than that in control subjects. Prothrombin
      time and activated partial thromboplastic time were significantly less in the
      patients group than that in the control group (P < 0.05). There were statistical
      difference. The parameters of blood biochemistry, whole blood cell count and
      platelet adhesion test of two groups had no significant difference (P > 0.05).
      CONCLUSION: Elevated plasma fibrinogen may be a major pathogenesis of SSHL. An
      increase in plasma fibrinogen level may lead to elevated plasma viscosity. All
      these may promote a prothrombin or hypercoagulable state and impair blood
      perfusion of cochlea.

PMID- 18338562
TI  - [The changes in vestibular function in patients with diabetes mellitus and its
      clinical significance].
AB  - OBJECTIVE: To study the changes of vestibular function in patients with diabetes
      mellitus and its clinical significance. METHOD: Electronystagmography (ENG) was
      used to examine 76 patients with diabetes mellitus and 60 healthy adults
      subjects. After clinical detection of vestibular function including spontaneous
      nystagmus, positional test, head shaking nystagmus, neck torsion test, caloric
      test, and sensory organization tests which consist of gaze, saccade and smooth
      pursuit test, the results of these two groups were recorded for qualitative and
      quantitative statistical analysis. RESULT: The rate of vestibular dysfunction in
      patients with diabetes mellitus were 68.4%. and that of the controls were 8.3%.
      There was significant difference between these two groups (chi2 = 15.472, P <
      0.01). CONCLUSION: Vertigo or dizziness occurred in patients with diabetes
      mellitus might be related to vestibular dysfunction. ENG test could be used as
      one of the objective clinical examinations in patients with diabetes mellitus.

PMID- 18338563
TI  - [Mutation analysis of GJB2, GJB3 and GJB6 gene in deaf population from special
      educational school of Chifeng city].
AB  - OBJECTIVE: To investigate the genetic causes of nonsyndromic deaf patients in
      special educational school of Chifeng city. Inner Mongolia by genetic screening
      testing method. This study focused on analyzing mutations of coding sequence of
      GJB2, GJB3 and GJB6 gene. METHOD: DNA were extracted out from peripheral blood of
      134 nonsyndromic deaf probands of Chifeng special educational school and 100
      normal hearing controls in northern China. First, GJB2 gene mutation was analyzed
      by direct sequencing for its only exon in the open reading frame. Individuals
      found with heterozygous GJB2 mutation were given further testing for GJB6
      del(GJB6-D13S1830) and direct sequencing for its exon. In 91 probands with
      unknown genetic cause (excluding probands who carried mtDNA A1555G mutation and
      GJB2 gene bi allele mutation and probands who were diagnosed as enlarged
      vestibular aqueduct by temporal CT), GJB3 gene mutation was analyzed by direct
      sequencing for its exon. RESULT: The sequencing results revealed that forty-one
      cases carried GJB2 mutation. of which twenty-two were homozygous or compound
      heterozygous and nineteen were heterozygous. Further testing for GJB6 del(GJB6
      D13S1830) and analysis of its coding sequence in GJB2 heterozygous cases showed
      no positive result. Four subjects in control group carried pathogenetic mutation
      of GJB2 gene. Six types of novel variants of GJB2 gene were detected. Of the 91
      deaf probands with unknown etiology. two probands were found carrying
      heterozygous pathogenetic mutation of GJB3 gene. one of whom also carried GJB2
      235delC heterozygous mutation. One subjects in the control group carried
      pathogenetic mutation of GJB3 gene. Three types of novel variants of GJB3 gene
      were found. CONCLUSION: By screening GJB2.GJB3 and GJB6 gene, we found 32.1%
      probands carrying GJB2, GJB3, and GJB6 mutations and we are able to determine
      genetic cause related to these three genes from one family for 16.42 percent of
      nonsyndromic deaf probands in special educational school of Chifeng city. The
      discovery of novel variants of GJB2 and GJB3 gene makes the mutational and
      polymorphic spectrum more plentiful in Chinese population.

PMID- 18338564
TI  - [The role of PET-CT in evaluation of recurrence and metastasis of head-and-neck
      tumor after definitive treatment].
AB  - OBJECTIVE: To explore the significance of 8F-FDG PET-CT in the diagnosis of the
      recurrence and metastasis of head-and-neck tumor after definitive treatment.
      METHOD: Forty-two patients having received definitive treatment for head-and-neck
      tumor of whom the tumor could not be identified clinically underwent 18F-FDG PET
      CT examination. Follow-up data could be obtained for all foci identified on PET
      CT images. PET-CT and CT accuracy was compared on the basis of follow-up and
      histopathologic findings. RESULT: A total of 103 foci were noted on PET-CT
      images. Identified by follow-up data, the sensitivity, specificity and accuracy
      were 92.55%, 42.11% and 84.07% respectively for CT examination, and 100.00%,
      52.63%, and 92.04% for PET-CT respectively. The sensitivity and accuracy of PET
      CT were significantly higher than those of CT (P < 0.05 or P < 0.01), whereas the
      difference in specificity between the results of these two groups was not
      significant (P > 0.05). CONCLUSION: The major benefits of FDG PET were that it
      differentiates scar and relapse, as well as detects LN and distant metastasis.
      Detailed clinical information and inclusion of results of morphological
      diagnostics are prerequisites for PET-CT final image interpretation, while scans
      should not be performed less than 6 weeks after definitive treatment.

PMID- 18338565
TI  - [The characteristics of VEMP in patients with acoustic neuroma].
AB  - OBJECTIVE: To establish the normal value of the vestibular evoked myogenic
      potential (VEMP), and to determine the characteristics of VEMP in patients with
      acoustic neuroma (AN) and to explore the significance of VEMP in diagnosis of AN.
      METHOD: Click-evoked VEMP was recorded with surface electrodes attached on the
      sternocleidomastoid muscle. Latencies and amplitudes of specific waveform of VEMP
      were measured. The hearing normal subjects including 26 males and 20 females were
      chosen to establish the normal value of VEMP. VEMP was investigated in 14
      patients with AN who underwent surgery during the period of 2006-2007 as well as
      auditory brainstem response (ABR) and vestibular caloric test. RESULT: Of 46
      subjects with normal hearing, VEMP was present in both ears in 43 subjects,
      absent in either ear in three subjects. The reducible rate is 93.5% (86/92). The
      nor-mal value obtained from 86 reducible ears were as follows (means +/- standard
      deviation): latency of p13 (11.86 +/- 2.11) ms, latency of n23 (18.57 +/- 2.19)
      ms, interval time between p13 and n23 (6.71 +/- 1.69) ms, amplitude of p13n23
      (24.18 +/- 8.22) microV. Interaural variances in 43 subjects whose VEMP were
      available were as follows (means +/- standard deviation): /deltap13 (0.64 +/-
      0.61) ms, /deltan23/(1.05 +/- 0.97) ms, interval time between /delta13n23/ (0.84
      +/- 0.81) ms, amplitude ratio (max/min) 1.32 +/- 0. 37, interaural asymmetric
      ratio of VEMP 0.12 +/- 0.11. Of the 14 patients with AN, VEMP was absent on the
      affected side in eight patients, absent on either side in three patients, and
      present on the unaffected side in 11 patients. VEMP presented on the affected
      side in three patients was significantly prolonged in /deltapl3/ and
      /deltap13n23/. CONCLUSION: Patients with AN characterized with VEMP could be
      useful in the diagnosis of AN combined together with other tests.

PMID- 18338566
TI  - [Clinical study of the bone conduction thresholds before and after tympanoplasty
      in chronic suppurative otitis media].
AB  - OBJECTIVE: To study the relative factors of the changes of preoperative and
      postoperative bone conduction thresholds in chronic suppurative otitis media.
      METHOD: The preoperative and postoperative bone conduction thresholds were
      prospectively investigated in 45 patients with unilateral chronic suppurative
      otitis media after tympanoplasty. Preoperatively (within 3 days before
      operation), 10 dB or more depression of bone conduction threshold at least in
      consecutive 2 frequencies between 0.25 kHz and 8.00 kHz was considered to be
      significant. Similarly in the postoperative period (3 months after operation), 10
      dB or more improvement or impairment of bone conduction threshold at least in
      consecutive 2 frequencies between 0.25 kHz and 8.00 kHz was regarded as
      significant. RESULT: Thirty-five of 45 cases (77.8%) were found to have depressed
      bone conduction threshold before operation, 6 of 35 cases (17.1%) had improved
      bone conduction thresholds and 5 of 45 cases (11.1%) had depressed bone
      conduction thresholds after tympanoplasty. CONCLUSION: In cases with chronic
      suppurative otitis media, successful results could be achieved after
      tympanoplasty disregarding air conduction threshold, the air-bone gap and
      deteriorated bone conduction threshold. Impairment of bone conduction thresholds
      could be induced by chronic suppurative otitis media itself and could also be
      induced by touching the ossicle chain crudely and by the noise of drilling during
      the operation.

PMID- 18338567
TI  - [In vitro and in vivo biodegradation of sustained-release vehicle poloxamer 407
      in situ gel].
AB  - OBJECTIVE: To observe the biodegradation of poloxamer 407 gel in acoustic capsule
      in vitro and in vivo, and to explore the applied perspective in the local drug
      delayed-release treatment for inner ear disorders. METHOD: Weighing the remained
      amount of poloxamer 407 gel at 37 degrees C at fixation time interval. The right
      ears of 15 healthy guinea pigs as experimental group were perfused with 20%
      poloxamer 407 solution 100 microl in round window niche, the left ears as control
      group with normal saline. The histology of bullae at 7, 14, 28, 49 days after
      perfusion was examined by means of serial section after paraffin imbedding.
      RESULT: The degraded amount were 20% and 25% in two groups respectively. The
      poloxamer 407 gel at 37 degrees C after 7 weeks was (78.89 +/- 13.10) microg and
      (75.32 +/- 8.94) microg respectively. The poloxamer gel in bullae was almost
      biodegraded and discharged 49 days after perfusion, only few gel remained in the
      middle ear cavity under light microscope. The morphology of the mucosa of middle
      ear cavity and round window membrane were not significantly damaged after
      poloxamer 407 perfusion. CONCLUSION: Poloxamer 407 biodegraded slowly, but it
      could be biodegraded in vivo or discharged via eustachian tube, and caused no
      inflammation and immunologic rejection on the middle ear cavity. Thus, poloxamer
      407 gel is suitable for the short-time sustained-release medical treatment in the
      inner ear diseases.

PMID- 18338568
TI  - [Comparison of phylogeny analysis methods for rhizobia asolated from Albizia
      spp., Acacia spp. and Leucaena leucocephala].
AB  - Multilocus house-keeping gene sequence analysis is a hotspot of taxonomy and
      phylogeny of prokaryotes. In this research, we used atpD and gln II gene
      sequences to analyze the phylogeny of nine rhizobia strains of Albizia spp.,
      Acacia spp. and Leucaena leucocephala and compared the results to that of 16S
      rDNA. The phylogenetic relationships based on the sequence analysis of these
      three genes were congruent at the genera level. CCBAU43060 and CCBAU 61139 were
      located in the branch of Rhizobium-Agrobacterium. CCBAU51471, CCBAU35220,
      CCBAU51276 and CCBAU61158 belonged to the genera of Mesorhizobium. CCBAU35234,
      CCBAU61178 and CCBAU35085 were assigned to Bradyrhizobium. Differences were found
      for some strains, for example CCBAU 61158, CCBAU43060, CCBAU61178, at the species
      level. Insertion fragment and mosaic gene were also found in some isolates. These
      results indicated that there was recombination between species in the same
      genera. It is reliable to determine the taxonomy status at genera levels based on
      the sequence analysis of 16S rDNA. If the relationships between strains belonging
      to the same genera were studied using the phylogeny methods, researches should be
      carried out with more than one house-keeping genes.

PMID- 18338569
TI  - [Molecular diversity of rumen Archaea from Jinnan cattle].
AB  - Molecular diversities of rumen archaea of Jinnan (South Shanxi Province, China)
      cattle was analyzed and compared by 16S rRNA gene sequencing from three clone
      libraries generated using three different archaea-specific primer sets,
      respectively. DNA from rumen of 4 Jinnan cattle was extracted, and methanogen 16S
      rRNA gene was amplified using archaea-specific primer sets. Three clone libraries
      were generated by using vector pGEM-T and cloning into E.coli JM109. One hundred
      clones were randomly picked up for each library and RFLP was analyzed for each
      clone to obtain OTUs. Sequences from each OTU were analyzed and compared with
      available sequences in GenBank. The first library, generated with primers Arch
      f364/1386, produced four groups of sequences, affiliated with 4
      Methanobrevibacter strains, 1Y (61% of clones), SM9 (23% of clones), NT7 (14% of
      clones), and AK-87(2% of clones). The second library, generated with primers 1
      Af/1100Ar, two groups of sequences, one affiliated with Methanobacterium
      aarhusense (72% of clones) and the other with Methanosphaera stadtmanae DSM 3091
      (28% of clones). The third library, generated with primers Met86F/Met1340R,
      produced a high degree of diversity. It included the sequence groups found in the
      first and the second libraries, as well as sequences affiliated with the
      Methanomicrobium mobile (2% of clones) and uncultured euryarchaeote sequences (7%
      of clones). The phylogenetic analysis indicated that archaea found in the three
      libraries were clustered in Methanobrevibacter, Methanobacterium, Methanosphaera,
      Methanomicrobium, and unidentified euryarchaeote of the Euryarcharota. There were
      25 unidentified sequences belonged to Euryarchaeota. This suggests the existence
      of novel methanogens in the rumen of Jinnan cattle.

PMID- 18338570
TI  - [Cloning and physical map construction of a large plasmid pBMB165 in Bacillus
      thuringiensis].
AB  - The largest detected plasmid pBMB165 from Bacillus thuringiensis subsp.
      tenebrionis strain YBT-1765 (H(8ab)) was cloned and its physical map was
      analyzed. For the cloning, two BAC libraries were constructed with their plasmid
      DNA and genomic DNA, respectively. The plasmid DNA BAC library was obtained by
      partially digesting plasmid DNA with BamHI and then cloning to pBeloBAC11 vector,
      whereas the genomic DNA BAC library was done with HindIII partial digestion. With
      the chromosome walking strategy, the plasmid BAC library was initially screened
      by the primers designed according the sequence coding replication protein Rep165
      on a previously identified 3.6kb DNA fragment (pBMB165-F4A). Finally, 5 clones
      covering the most of plasmid pBMB165 were obtained. When screening the genomic
      DNA BAC library, 8 clones covering whole plasmid pBMB165 were isolated. By
      restriction analysis of these 13 BAC clones, the physical map and the linear
      linkage map of plasmid pBMB165 were constructed and the size of pBMB165 was
      calculated to be 82kb. Based on the DNA sequence of the BAC insertion ends and a
      previously published 20kb fragment on recombinant plasmid pBMB165A2, there were
      redundant transposable elements appeared on this large plasmid. This study
      provided a novel way to clone large plasmid from B. thuringiensis, to draw the
      physical map by construction of BAC library, and to dissolve the problem in
      cloning large plasmid from B. thuringiensis.

PMID- 18338571
TI  - [Disruption of zwf2 gene to improve oxytetraclyline biosynthesis in Streptomyces
      rimosus M4018].
AB  - Genes of zwf1 and zwf2 encode two isozymes of glucose-6-phosphate dehydrogenase
      (G6PDH) of Streptomyces, respectively. G6PDH is the first enzyme in the oxidative
      pentose phosphate pathway (PPP) and the key enzyme for NADPH generation. Based on
      thermal sensitive plasmid pKC1139, a recombinant plasmid pKC1139-zwf2' was
      constructed and verified with restriction enzyme digestion. The plasmid pKC1139
      zwf2' was electropolated into competent Streptomyces rimosus M4018 cells after it
      was demethylated by E. coli GM2929. Transformants grown on Tryptone Soya Agar
      (TSA) plate containing 500 ug/mL apramycin were selected, and identified using
      dot hybridization analysis and PCR amplification with apramycin resistant gene as
      primers. A positive clone was then selected and designated M4018-delta zwf2. With
      parent strain S. rimosus M4018 as control, mutant M4018-delta zwf2 was cultured
      in shaking flask. Specific acitivity of G6PDH of M4018-delta zwf2 was only half
      of that of parent strain whereas yield of oxytetracycline (OTC) of mutant was 27%
      higher to the mutant had a similar biomass profileto that of the control
      biosynthesis started when the growth entered stationary phase on the 4th day.
      However, specific oxytetracycline production of mutant was 31% higher than that
      of the parent strain, indicating that zwf2 disruption could enhance
      oxytetracycline biosynthesis in S. rimosus M4018-delta zwf2.

PMID- 18338572
TI  - [Energy charge changing by pathway manipulation of adenosine triphosphate
      metabolism in Escherichia coli].
AB  - Endocystic metabolism of energy and material is a complex matrix. We do not know
      the consequence of replacing the genes controlling the metabolic fluxes. Single
      gene (add) deletion cannot change the direction of metabolic fluxes of adenosine.
      Through deleting 3 genes, namely add (encoding adenosine deaminase [EC:3.5.4.4]),
      deoD (encoding purine-nucleoside phosphorylase [EC:2.4.2.1]) and amn (encoding
      AMP nucleosidase [EC:3.2.2.4]), and introducing ado1 gene(encoding adenosine
      kinase in S. cerevisiae[EC:2.7.1.20]), we modified the salvage pathway of adenine
      metabolism, and constructed a strain named J991. Extract of J991 was analyzed by
      HPLC. The endocystic concentration of ATP, ADP and AMP raised 2-fold as the
      control, and the metabolic fluxes of adenosine are also changed. It is a new way
      for ATP stimulation. Multi-gene manipulation is more effective than single-gene
      manipulation in salvage pathway of adenine.

PMID- 18338573
TI  - [Classification of Streptomyces strain Z314 and purification of its product
      pravastatin].
AB  - Actinomycete strain Z314 with the capability of converting compactin to
      pravastatin was isolated from soil samples. Based on the results of
      morphological, physiological, chemotaxonomic characteristics and 16S rRNA
      analysis, strain Z314 was placed within the genus Streptomyces and identified as
      the species Streptomyces xanthochromogenes. The production of pravastatin reached
      1580 mg/L under optimized feeding of compactin, and the conversion rate was
      49.45%. With the efficient purification system by fibrin column, macroporous
      adsorption resin and high performance liquid chromatography, pravastatin was
      purified from the culture supernatant with an overall recovery of 45.06% and
      purity of 99.02%. It is the first report in the world to produce pravastatin by
      converting compactin using Streptomyces xanthochromogenes under optimized
      conditions, the conversion of compactin to pravastatin was higher than other
      methods reported. The recovery and purity were improved by the three-step
      purification of pravastatin from the culture supernatant.

PMID- 18338574
TI  - [Enterobacter agglomerans B1 producing beta-galactosidase with transglycosylation
      activity: screening, identification, fermentation conditions, and galacto
      oligosaccharides synthesis].
AB  - Galacto-oligosaccharides (GOS) are promising non-digestible oligosaccharides
      recognized as prebiotics. Commercial GOS containing galactose as subunit, are
      synthesized from lactose using the galactosyl-transferase activity of beta
      galactosidase. A strain producing beta-galactosidase with transglycosylation
      activity was screened from the soil. Phenotypic analysis including morphology and
      physiology characteristics and 16S rDNA sequence analysis were carried out. Based
      on taxonomy results, the strain was identified as Enterobacter agglomerans B1.
      Medium and fermentation conditions were optimized by single factor and orthogonal
      experiments. The enzyme reached 9.7 U/mL in the medium (pH 7.5) containing 1%
      lactose, 1% yeast extract, and 0.5% peptone when cultured at 25 degrees C for 26
      h. Effects of pH, temperature, lactose concentration, and reaction time on
      transgalactosylation by whole cells were studied. Yield of GOS reached 40.7% in
      30% lactose (pH 7.5) at 50 degrees C for 12 h, as analyzed by HPLC and TLC. The
      results of an MS analysis showed that GOS were composed of di, tri-, and
      tetrasaccharides.

PMID- 18338575
TI  - Construction of a genetically engineered and stable strain of degrading gamma
      hexachlorocyclohexane and carbendazim by transposon mini-Tn5.
AB  - The complete dehydrochlorinase gene linA of a gamma-hexachlorocyclohexane (gamma
      HCH) degrading strain Sphingomonas sp. BHC-A, containing promoter and Shine
      Dalgarno sequence (SD sequence), was amplified by PCR. The linA gene was inserted
      into NotI-cut transposon vector pUT/mini-Tn5 (Km(r)) to get a novel transposon
      vector pUT/mini-Tn5-linA. With the helper plasmid RK600, the transposon vector
      pUT/mini-Tn5-linA was introduced into one carbendazim degrading gram-positive
      strain Rhodococcus sp. DJL-6 by triparental conjugation and then the
      dehydrochlorinase gene linA was integrated into the chromosome of Rhodococcus sp.
      DJL-6 by the transposon mini-Tn5. The selected multifunctional genetically
      engineered strain DJL-6A could degrade gamma-HCH and carbendazim simultaneously.
      The dehydrochlorinase activity of DJL-6A was as strong as that of Sphingomonas
      sp. BHC-A in 0.05 and 5 microg/mL initial gamma-HCH concentration. The linA of
      the strain DJL-6A was genetically stabile after successive plating DJL-6A for 30
      days on nonselective media.

PMID- 18338576
TI  - [Isolation and identification of a novel phosphate-dissolving strain P21].
AB  - Phosphate-dissolving microorganisms can be applied for better use of insoluble
      phosphorus as fertilizer., A phosphate-dissolving strain P21 was isolated from
      soil samples in China. The isolate was identified as Erwinia herbicola var.
      ananas, based on its 16Sr DNA sequence and physiological characteristics. Its
      activity was measured in solid media as well as liquid media using different
      phosphate sources including tricalium phosphate, hydroxyapatite, ferric
      phosphate, aluminium phosphate, zinc phosphate, and rock phosphates. E. herbicola
      could strongly dissolve 1206.20 mg tricalium phosphate and 529.67 mg
      hydroxyapatite in per liter liquid media. The strain showed high phosphate
      dissolving ability for rock phosphates from Jinning and Kunyang in Yunnan
      province, Yaan in Sichuan province and Jinping in Jiangsu province with the
      capacity of 6.64 mg, 78.46 mg, 67.07 mg and 65.24 mg soluble phosphate
      respectively per liter medium, whereas the phosphate-dissolving ability to the
      rest of the eight rock phosphates was weak. According to the experiments, the
      phosphate-dissolving ability of E. herbicola was specific to different rock
      phosphates, and phosphate-dissolving ability of E. herbicola was not directly
      related to pH reduction of liquid media.

PMID- 18338577
TI  - [Construction of the gene drb0099 deleted mutant and adversity analysis in the
      extremely radioresistant bacterium Deinococcus radiodurans].
AB  - Deinococcus radiodurans R1 has extraordinary resistance to radiation. DRB0099
      might play an important role in protecting the bacterium against radiation. To
      verify the inference, we deleted drb0099 and constructed the mutant. Comparing
      with the wild type, the mutant grew more slowly in the beginning cultivation
      stage (0-16 h) under normal conditions. After being cultivated for 16 h, the
      mutant grew faster than the wild type. The biomass concentration of the wild type
      was always higher than that of the mutant. The mutant cell's fission during the
      growing phase might be blocked. When treated with UV, although Deinococcus
      radiodurans R1 cultures' survival fraction was lower with UV treatment time
      increased, the survival fraction was much higher than that of drb0099. The wild
      type could repair DNA double strands breaks better than the mutant. The gene
      drb0099 might directly relate with the DNA repair system. The mutant was more
      sensitive to H202 than the wild type. The wild type could better protect protein
      and DNA against reactive oxygen species (ROS) or in DNA repair. When treated with
      low concentration of H2O2, although the survival fraction of both R1 and the
      mutant decreased, the difference was small. However, with the concentration of
      H2O2 increased, the difference value increased. The mutant without drb0099 was
      more easily injured than the wild type with ROS increased. Under UV or H2O2
      treatment, DRB0099 could protect protein and DNA from oxidation.

PMID- 18338578
TI  - [Wolbachia extensively harbored by Bemisia tabaci in China].
AB  - Wolbachia are a group of maternally inherited bacteria harbored by a variety of
      arthropods and can manipulate the reproductivity of their hosts. Eighteen
      populations of whiteflies were collected from Hebei, Xinjiang, Beijing, Shandong,
      Zhejiang, Guangxi, Hainan, Guangzhou and Fujian provinces, China. These
      whiteflies were molecularly identified using internal transcribed spacer 1 ITS1
      rDNA sequences. They were then detected for Wolbachia infection using Wolbachia
      specific primers designed based on 16S rDNA and wsp gene sequences. The results
      showed that almost all populations were detected positive for Wolbachia
      infection. Whiteflies of B/Q group mainly carried Wolbachia belonging to
      supergroup A, while non- B/Q whiteflies were commonly detected for Wolbachia
      superinfection. This study indicated that the infection rate of Wolbachia in
      natural populations of B. tabaci might be much higher than expected, and the
      threshold of detection methods may be one of the key factors influencing
      detection of Wolbachia infection.

PMID- 18338579
TI  - [Identification and characterization of a novel infection-related factor (cell
      wall hydrolase/autolysin) of Streptococcus suis serotype 2].
AB  - Streptococcus suis serotype 2 (SS2) is an economically important, zoonotic agent
      causing death and disease in both human and swine. According to published SS2
      European strain P1/7 complete genomic sequence, primers for detection and
      amplification autolysin were designed. Autolysin gene was detected by PCR with
      genomic DNA of HA9801 (Jiangsu isolate), ZY05719 (Sichuan isolate), ATCC43765
      (reference strain), other SS2 isolates from different regions, and strains of
      other different serotypes (such as serotype 1, 1/2, 7 and 9). PCR results showed
      that all 27 SS2 virulent isolates harbored gene autolysin, but not in non
      virulent SS2 strain. Among other serotypes, only serotype 7 strain had this gene.
      The complete autolysin genes of HA9801 and ZY05719 were respectively amplified by
      PCR and sequenced. Their putative protein sequences were analyzed through online
      software, results showed both had six repeated domain "GBS_Bsp-like" and one
      domain "N-acetylmuramoyl-L-alanine amidase". In addition, sequence similarity
      analysis demonstrated that autolysins of the two strains (HA9801 and ZY05719)
      showed high homologue to that of European strain P1/7 (99.8%), but obviously
      differed from Canada strain 89/1589, the latter lacked one domain "GBS Bsp-like".
      Software DNASTAR was used to analyze autolysin protein sequence and predicted its
      putative antigenicity. Then partial antigentic segment of autolysin was
      amplified, cloned and inserted into expression vector pET30a(+), and induced by
      IPTG to express recombinant autolysin. Its reactivity was analyzed by SDS-PAGE
      and western blot with swine convalescent sera, blot result showed that the
      recombinant protein had good reactivity and could be considered as a vaccine
      candidate.

PMID- 18338580
TI  - [Generation of nalidixic acid-resistant strains and signature-tagged mutants of
      Actinobacillus pleuropneumoniae].
AB  - Actinobacillus pleuropneumoniae is a very important respiratory pathogen for
      swine and causes great economic losses in pig industry worldwide. Signature
      tagged mutagenesis (STM) is an effective method to identify virulence genes in
      bacteria. In this study, we selected nalidixic acid-resistant strains of APP
      serotypes 1 and 3 by in vitro cultivation, and used as receipt strains for
      constructing transposon mutants by mating with E. coli CC 118 lambdapir or S17-1
      lambdapir containing mini-Tn10 tag plasmids pLOF/TAG1-48, with or without the
      help of E. coli DH5alpha (pRK2073). We screened mutant strains by antibiotics
      selection, PCR and Southern blot identification. Our data revealed that nalidixic
      acid-resistance of APP strains could easily be induced in vitro and the
      resistance was due to the mutation in the DNA gyrase A subunit gene gyrA. In the
      mating experiments, the bi-parental mating was more effective and easier than tri
      parental mating. Different APP strains showed a different mating and transposon
      efficiency in the bi-parental mating, with the strains of serotype 1 much higher
      than serotype 3 and the reference strain of serotype 3 higher than the field
      strains. These data were helpful for the construction of STM mutants and pickup
      of virulence genes of APP.

PMID- 18338581
TI  - [Localization analysis of attenuated Salmonella typhimurium with oral
      immunization].
AB  - To analyze the localization of attenuated Salmonella typhimurium after oral
      immunization. Prokaryotic expression plasmid pYA33-DsRed, carrying the RFP gene,
      was constructed and electro-transformed into an attenuated strain X4550 of
      Salmonella typhimurium, the recombinant bacteria were named as X4550 (33-DsRed).
      The macrophage cell line RAW264.7 and bone marrow dendritic cell (BMDC) were
      invaded by X4550 (33-DsRed) in vitro. Furthermore, BALB/c mice were immunized
      with recombinant bacteria orally. RFP positive cells (RFP+ cells) were detected
      by Flow Cytometry (FCM) from spleen, liver, Mesenteric lymp node (MLN), Peyer's
      patch (PP), Inguinal lymph node (ILN). The invasion rate increased when the
      multiplicity of infection(MOI) were improved in this two kinds of cells
      respectively. After oral immunization with X4550 (33-DsRed), RFP+ cells were
      detected by FCM on 1d, 2d, 3d, 5d, 7d in spleen, liver, MLN, PP, ILN cells. The
      first day, RFP+ cells were detected in MLN and PP, and in PP at a higher rate of
      1.4% than that of MLN. 0.4% RFP+ cells were detected the next day in ILN. On 3th
      day, the rates of RFP+ cells were increased in all of above tissues or organs and
      decreased on the 5th day. At the 7th day, RFP+ cells couldn't be detected in all
      tissues or organs tested. It is suggested that the invasion ability and the
      transfer through mucosal pathway and targeting to recognize immune tissue or
      organs are favor of the research in mucosal vaccine and the vaccine efficiency.

PMID- 18338582
TI  - Characterization and potential use of truncated PCV2 capsid protein and its
      polyclonal antibody for diagnosis of PCV2 infections.
AB  - As porcine circovirus 2 (PCV2) ORF2 encodes the major structural protein (capsid)
      that is closely related to the pathogenesis, the capsid (Cap) protein could be
      used as a target antigen for serological analysis. The immunoactivities of the
      truncated capsid proteins containing immunogenic epitopes of PCV2 (Cap2s) or PCV1
      (Cap1s) expressed in Escherichia coli were described, as well as the
      characteristic of their polyclonal antibodies in diagnosis of PCV2 infection.
      Western blot analysis revealed that both Cap2s and Cap1s gave strong signals on
      nitrocellulose membranes to their corresponding polyclonal antibody. Furthermore,
      either PCV2-positive sera from PMWS cases or PCV1-positive swine sera could only
      recognize Cap2s or Capls, respectively. There was also no cross-reactivity
      between the two polyclonal antibodies when reacted with natural Cap proteins of
      viral particles on cells by immunofluorescence assay (IFA). Thus, an ELISA was
      then developed using PCV2 Cap as coating antigen to evaluate the sero-prevalence
      of PCV2 infection in pigs. The PCV2-positive rate ranged from 48.28% to 100%
      among different herds (n = 13) with an average of 80.69% (209/259). These results
      indicate that Cap2s was type-specific and could be used as a discriminative
      antigen for monitoring PCV2 antibody in serum. The polyclonal antibodies were
      also useful for differential identification of PCV1 and PCV2 infection by
      immunohistochemistry.

PMID- 18338583
TI  - [The N1-18 terminus of Marek's disease virus VP22 is essential for protein
      transduction].
AB  - We previously showed some differences in Marek's disease virus (MDV) VP22 gene
      between virulent and avirulent strains, in the deletion from 201aa to 206aa,
      namely 201TKSERT206. In this study, VP22 genes were amplified from strains:
      CVI988/Rispens and GA. And then the fragments were subcloned into
      pcDNA3.1/zeo(+), respectively, which were co-expressed with an enhancer green
      fluorescent protein (EGFP) after transfection into COS-1 cells. As with both
      human herpesvirus 1 and bovine herpesvirus 1 VP22-EGFP fusion proteins, the
      subcellular localization of the three MDV EGFP-VP22 products revealed few
      differences, which bind to microtubules and nucleus membrane, and then to
      heterochromatin. In addition, VP22s also bind to centrosomes and inter-membrane.
      During mitosis, EGFP-VP22s bind to sister chromatids, but dissociates from the
      centrosomes and the microtubules of the mitotic spindle. In truncated fragments'
      transfection experiments, stained with the specific monoclonal antibody against
      VP22, it concluded that the full length of VP22 was required for protein
      transduction, and N1-18aa was essential to VP22 translocating from cytoplasm to
      nucleus as a potential nucleus localization site in the absence of other viral
      factors in MDV-1.

PMID- 18338584
TI  - [Prokaryotic expression of N-terminal antigenic domain of duck plague virus gB
      protein and the establishment of putative indirect ELISA assay].
AB  - Based on the antigenic analysis of duck plague virus (DPV) gB protein, we
      designed a pair of primers to amplify the gene fragment encoding high antigenic
      domain of DPV N-terminal gB protein from the DPV genome. The cloned gene was
      digested with EcoR I and Hind III and then inserted into pET32a vector to obtain
      the recombinant pET-gB1 plasmid. The recombinant plasmid was transformed into E.
      coli BL21, and expressed in very high level after induced with IPTG. The
      expressed product was analyzed by SDS- PAGE and Western blotting. The result
      indicated that the fusion protein (pET-gB1) existed as inclusion body, which was
      about 42.4kDa and showed specific immunoreactivity with anti-DPV sera. The
      recombinant gB1 protein was purified with His-Bind resin protein purification
      procedure. Then an indirect ELISA was established to detect antibody against DPV
      with the purified gB1 protein as the coating antigen. The result showed that the
      optimal concentration of coated antigen was 6.5 microg/mL and the optimal
      dilution of serum was 1 : 80. The positive criterion of this ELISA assay was
      OD(the tested serum) > 0.4 and OD(the tested serum)/OD(the negative serum) > 2.0.
      The ELISA was done on 700 sera that were preserved in Shandong, Jiangsu
      Provinces, and were detected by igB1-ELISA and iDPV-ELISA with duck plague virus
      as the coating antigen respectively. The agreement ratio between the two methods
      was 95.6%.

PMID- 18338585
TI  - [Differential expression of virulence and potential virulence genes of avian
      pathogenic Escherichia coli in vitro with DNA microarray analysis].
AB  - We constructed avian pathogenic Escherichia coli (APEC) specific DNA microarray
      to analyze the transcriptomes of APEC highly pathogenic strain E058 and low
      pathogenic strain E526 (both belonging to O2 serotype). For cultures in Luria
      Bertani (LB) broth medium, 16 distinctly expressed genes were observed in strain
      E526, and all of them were down-regulated. For cultures in the serum of chickens,
      15 distinctly expressed genes were screened in strain E526, and all of them were
      also down-regulated. The results suggest that DNA microarray could be used to
      screen distinctly expressed genes among virulence- and potential virulence
      associated genes of APEC. The expression of 11 common virulence- or potential
      virulence-associated genes were down-regulated for strain E526 compared to those
      of strain E058 cultured both in LB broth and chicken serum. Meanwhile, 4
      potential virulence-associated genes, aes-3, aes-10, aes-13 and aes-15 were down
      regulated for strain E526 but not for strain E058, when they grew in the chicken
      serum. Besides known virulence factors, we observed 10 new potential virulence
      related genes including aes-1, aes-2, aes-3, aes-4, aes-6, aes-8, aes-10, aes-13,
      aes-15 and aes-31.

PMID- 18338586
TI  - [Microplate for high throughput screening of 6-hydroxynicotinic acid transforming
      strains].
AB  - Recently, new insecticides containing 3-chloropyridylmethyl group as a versatile
      building block have been developed, among which imidachloprid is a promising one.
      The synthesis of imidachloprid can use 6-Hydroxynicotinic acid, the first
      intermediate of the bacterial degradation of nicotinic acid, as a starting
      material. It is difficult to hydroxylate nicotinic acid at C6 position in a
      chemical synthesis. However, biotransformation can produce 6-hydroxynicotinic
      acid with industrial application possibility. Therefore, methods for large scale
      screening of 6-hydroxynicotinic acid-producing microorganisms are urgent. A high
      through-put screening method for 6-hydroxynicotinic acid transforming strains was
      established by determining 6-hydroxynicotinic acid based on 96-well Microplate
      Multiskan Spectrum. The determination wavelength and the reference wavelength of
      6-hydroxynicotinic acid were 251nm and 231nm respectively. Beer's law is obeyed
      in the range of 0.5-11 microg/mL (R2 = 0.9999) for measuring 6-hydroxynicotinic
      acid. The average recovery rate was 99.11%-100.81%. The results showed that there
      was no apparent difference between our microplate method and previous HPLC method
      in the detecting 6-hydroxynicotinic acid formation. The microplate method is
      simple, convenient and accurate. It has the potential for large scale (about 2000
      - 5000 reactions/d) screening of 6-hydroxynicotinic acid-producing
      microorganisms.

PMID- 18338587
TI  - [Purification and identification of iturin A from Bacillus subtilis JA by
      electrospray ionization mass spectrometry].
AB  - Lipopeptides produced by Bacillus subtilis JA antagonized a broad spectrum of
      plant fungal pathogens. The purification and identification of the lipopeptide
      antibiotics plays an important role for further research. Crude lipopeptides were
      extracted with methanol from the precipitate, which was obtained by adding 6mol/L
      HCl to the cell-free culture broth and then stored at 4 degrees C overnight. The
      crude extract was run on reversed-phase HPLC system with a Diamonsil C18 column
      (250 mm x 4.6 mm, Dikma) to separate the lipopeptides. Two antifungal compounds,
      which had strong inhibitory activity against various plant fungal pathogens, such
      as Fusarium graminearum, were purified. The molecular weights of two compounds
      were determined by electrospray ionization mass spectrometry (ESI/MS). Two
      compounds, with molecular weights of 1042.4 Da and 1056.5 Da, were homologues
      differed by a structure of -CH2. ESI collision induced dissociation mass
      spectrometry analysis was used to sequence the structure of purified compounds.
      Typical b- and y- type fragments showed that compound 1 (with a molecular weight
      of 1042.4 Da) had a primary structure of Pro-Asn-Tyr-PAA-Asn-Tyr-Asn-Gln (PAA
      represented beta-amino acid), which was consistent with lipopeptide iturin A.
      Compound 2 was a homologue of iturin A.

PMID- 18338588
TI  - [Properties of alkaline pectate lyase from recombinant strain E. coli JM109 (pHsh
      PL)].
AB  - Alkaline pectate lyase (PL) from recombinant strain E. coli JM109 (pHsh PL) was
      purified by a three-step process including (NH4)2SO4 precipitation followed by
      dialysis and chromatography. The purified enzyme appeared homologous on SDS-PAGE.
      The specific activity of the purified enzyme reached 1079 U/mg. The optimal pH
      and temperature were in the ranges of pH 9.0 to 10.0 and 50 degrees C to 66
      degrees C. The enzyme was preferable in optimal pH range in enzymatic retting of
      flax. Enzyme activity slightly increased in the presence of Mg2+ ion, whereas
      decreased in the presence of other ions, especially Fe2+. The K(m) of the
      purified enzyme for polygalacturonic acid was 20.93 mg/L, the V(max) for
      polygalacturonic acid hydrolysis was 105.3 micromol of unsaturated products per
      min and Ea was 21.74 kJ/mol. The results of the decay constant (k(d)) analysis on
      condition of PL bonding polygalacturonic acid (k(d) = 0.02 min(-1)) and PL
      without polygalacturonic acid (k(d) = 0.0342 min(-1)) showed the substrate was
      helpful to decrease thermal inactivation of PL. The products (unsaturated
      oligomers) from polygalacturonic acid degraded by PL were analyzed by
      electrospray ionization mass spectrometry(ESI-MS). The following data were
      obtained: ESI-MS m/z, 350.82 (unsaturated bigalacturonic acid, uG2), 527.04
      (unsaturated trigalacturonic acid, uG3). However, m/z 175 (unsaturated
      galacturonic acid, uGI) was not found. These results indicate that the final PGA
      degradation products was a mixture of unsaturated oligo-galacturonides including
      uG3 and uG2 except for uG1. It suggests that the recombinant PL cannot degrade
      uG3 and uG2.

PMID- 18338589
TI  - [An update of Streptomyces eukaryotic-type Ser/Thr protein kinases--a review].
AB  - We review briefly the strategies and processes to identify Ser/Thr protein
      kinases from Streptomyces spp. and discussed in detail the functions of well
      studied Ser/Thr protein kinases, such as the AfsR-kinase(AfsK), We used
      bioinformatic methods to predict transmembrane regions in Ser/Thr protein kinases
      of S. coelicolor A3(2) and S. avermitilis. The complete sets of Ser/Thr protein
      kinases from genomes of Streptomyces coelicolor A3(2) and Streptomyces
      avermitilis MA-4680 were categorized based on domain analyses.

PMID- 18338590
TI  - [Lactic acid bacteria growing at low temperature with a high exploitability--a
      review].
AB  - At present, increasing attentions have been paid to lactic acid bacteria because
      of their probiotic effects. In the nature, there exists a kind of lactic acid
      bacteria growing at low temperature with a long history of use. However, they
      have not been well studied and developed. Most articles about the lactic acid
      bacteria growing at low temperature focused on meat and fish storage at low
      temperature, or Kimchi, a kind of fermented vegetable. Many microorganisms
      studied are Leuconostoc and Lactobacillus species. Nevertheless, a few researches
      in this field are reported in China. In this paper, we review the living
      environment, varieties and functions of lactic acid bacteria growing at low
      temperature, to provide an overview for further studies. We also discuss
      perspectives of further development and utilization of these lactic acid
      bacteria.

PMID- 18338591
TI  - [Research advances in pharmacology of aucubin and aucubigenin].
AB  - The advances in the research on pharmacological activities of aucubin have been
      summarized in the last ten years. Aucubin is one of active components of Chinese
      medicinal herbs such as Eucommia ulmoides and has been shown wide pharmacological
      activities including hepatoproective, antitoxicanti-inflammatory, antioxidant,
      antiaging, antiosteoporosis and neurotrophic and should be further researched and
      utilized.

PMID- 18338592
TI  - [Effects of formula fertilization to yield and content on polysaccharide of
      Isatis indigotica].
AB  - OBJECTIVE: To select the optimum formula fertilization of Isatis indigotica
      through analyzing the yield and contents of polysaccharide of Radix Isatis for
      different treatments. METHOD: An orthogonal experiment design on the basis of
      three factors and four levels was applied for studying the effect of formula
      fertilization on yield. The contents of polysaccharides were determined with
      phenol-witriolic colorimetry. RESULT: The optimum formula fertilization of Radix
      Isatis was carbamide 869.0 kg x hm(-2), superphosphate 1 428.6 kg x hm(-2) and
      potassium sulfate 0 kg x hm(-2). CONCLUSION: Superphosphate can observably
      influence the yields of Radix Inditis. while carbamide influence the contents of
      polysaccharide of Radix Inditis.

PMID- 18338593
TI  - [Study on secondary metabolic organ of echinacoside in herbs of Cistanche
      tubulosa].
AB  - OBJECTIVE: It could give some theory support of confirming the secondary
      metabolism organ and regulation of echinacoside in Cistanche tubulosa by
      searching parasitic growth of C. tubulosa ahd echinacoside variation in different
      organs of host and parasite. METHOD: The echinacoside content was analyzed by
      HPLC. The relationship between dry matter accumulation and echinacoside
      accumulation of C. tubulosa as the well as root diameter of host were
      comparatively analyzed. RESULT: With the increase of dry matter accumulation of
      C. tubulosa, echinacoside accumulation increased significantly, and both of them
      were in significantly positive correlated with the root diameter of host.
      Echinacoside content in haustorium phloem was 15.53%, higher than that of
      haustorium xylem, C. tubulosa plant and other organs. CONCLUSION: Haustorium
      phloem was probably the secondary metabolism organ of echinacoside in C.
      tubulosa.

PMID- 18338594
TI  - [Preparative separation of gentiopicrin from Radix Gentianae by high-speed
      counter-current chromatography with macroporous resin].
AB  - OBJECTIVE: To develop a method for the preparative separation of gentiopicrin
      from Radix Gentianae by high-speed counter-current chromatography (HSCCC).
      METHOD: The crude alcohol extracts were eluted on a macroporous resin column and
      then purified by high speed counter-current chromatography (HSCCC). A two-phase
      solvent system composed of ethyl acetate: n-butanol: water (2 : 1 : 3) was used,
      and the lower phase was used as the mobile phase at a flow rate of 1.5 mL x min(
      1), while the apparatus rotated at 800 r x min(-1) and the eluate was detected at
      254 nm. RESULT: 136 mg gentiopicrin with purity of 99.6% determined by HPLC were
      obtained from 300 mg crude extraction only in one-step separation and less than
      200 minutes. CONCLUSION: The established method is simple, high efficiency and
      suitable for large-scale separation of gentiopicrin.

PMID- 18338595
TI  - [Fast and simultaneous determination of four index components in Qingwei
      Huanglian tablets by RP-HPLC].
AB  - OBJECTIVE: To establish a RP-HPLC method for fast and simultaneous determination
      of four index contents, which are Genpioside, Baicalin, Berberine Hydrochloride
      and Ammonium Glyeyrrhizinate, in Qingwei Huanglian tablets. METHOD: A separation
      was well achieved by gradient elution on a Hypersil C18 (4.6 mm x 250 mm, 5
      microm) column with the mobile phases of acetontrile -0.5% triethylamine water
      solution (pH 3.0) at a flow rate of 1.0 mL x min(-1), detection wavelength of 230
      nm, and room temperature. RESULT: The calibration curve were linear in the ranges
      of 4.82-77.2, 5.80-92.8, 1.63-26.1 and 6.40-102 microg x mL(-1) (r = 0.9997
      0.9999) for genpioside, baicalin, berberine hydrochloride and ammonium
      glyeyrrhizinate, respectively. The average recoveries of four index components
      were not less than 98.0%. CONCLUSION: The method is convenient, rapid and
      accurate. It is suitable for the quality control of Qingwei Huanglian tablets.

PMID- 18338596
TI  - [Studies on factors influencing on ephedrine contents in Maxing Shigan
      decoction].
AB  - OBJECTIVE: To investigate the factors influencing on the ephedrine contents in
      different compositions of Maxingshigan decoction. METHOD: Adopt mixed uniform
      design to dismantle recipes, employ the stepping regression analysis to deal with
      experimental statistics, use the partial correlational analysis to analyze the
      correlation coefficients and the results were validated. RESULT: The regressive
      equation was of significance, that is Y = 4.36719347 + 7.752707437X1 +
      1.2557197041X3 (r = 0.85564, P = 0.0189). The main influencing factors on
      ephedrine content in Maxingshigan decoction were gypsum and amygdalin. The
      influent factor of amygdalin on ephedrine content had great significance, and
      gypsum had significance. CONCLUSION: The collective effects of amygdalin and
      gypsum affect the content of ephedrine in Maxing Shigan decoction which the
      content-effect relationship was in direct correlation.

PMID- 18338597
TI  - Chemical constituents from aerial part of Curcuma wenyujin.
AB  - OBJECTIVE: To investigate the chemical constituents from aerial part of Curcuma
      wenyujin. METHOD: Compounds were isolated by repeated column chromatography on
      silica gel. Their structures were elucidated on the basis of spectral analysis
      and comparison with literature data. RESULT: Six compounds were isolated and
      identified as codonolactone (1), voleneol (2), octacosanoic acid (3), beta
      sitosterol (4), mangdesisterol (5), and daucosterol (6). CONCLUSION: Compounds 1,
      2, and 5 were isolated from the plant for the first time.

PMID- 18338598
TI  - [Terpenoid glycosides from stem of Luculia pinceana].
AB  - OBJECTIVE: To study the chemical constituents from n-BuOH portion of ethanolic
      extract from the stem of Luculia pinceana. METHOD: The column chromatographic
      techniques were applied to isolate constituents. A combination of IR, FAB-MS, NMR
      and 2D NMR spectroscopy was used to identify structures. RESULT: Seven compounds
      were isolated from the n-BuOH fraction and their structures were elucidated as
      vogeloside (1), epi-vogeloside (2), loganoside (3), loganin (4), cincholic acid
      28-O-beta-D-glucopyranosyl ester (5), cincholic acid-3-O-beta-D-glucopyranoside,
      28-O-beta-D-glucopyranosyl ester (6), cincholic acid-3-O-beta-D-glucopyranoside
      (7). CONCLUSION: Compounds 1-7 were isolated from the genus for the first time.

PMID- 18338599
TI  - [Studies on chemical constituents of Laurencia tristicha ( II )].
AB  - OBJECTIVE: To search for chemical constituents with structural diversity from
      Laurencia tristicha to supply for biological assay. METHOD: Compounds were
      isolated by means of column chromatography over normal phase silica gel and
      Sephadex LH-20, recrystallization and HPLC. Structures were identified by
      spectroscopic methods including 1D NMR, IR and MS. Cytotoxicities of the purified
      compounds were evaluated by MTT method. RESULT: Seven compounds were isolated
      from L. tristicha. Their structures were elucidated as cholesterol (1), cholesta-
      5-en-3beta, 7alpha-diol (2), beta-stigmasterol (3), phytol (4), zeaxanthin (5), 4
      -hydroxybenzaldehyde (6), indolyl-3-carbaldehyde (7). In the cytotoxic assay
      compound 2 was active against human cancer cell lines HCT-8, Bel-7402, BGc-823,
      A549 and HELA with IC50 values of 1.90, 2.02, 1.99, 6.52 and 1.20 microg x mL(
      1), respectively. Compound 4 showed cytotoxicity against HCT-8 and HELA with IC50
      value of 3.51 and 2.04 microg x mL(-1), and other compounds were inactive ( IC50
      > 10 microg x mL(-1)). CONCLUSION: Compounds 1-7 were isolated from L. tristicha
      for the first time. In additon, compounds 2 and 4 were cytotoxic against several
      human cancer cell lines.

PMID- 18338600
TI  - [Studies on solid phase extraction method of aristolochic acids and
      aristololactams in rat urine].
AB  - OBJECTIVE: To develop a urine pretreatment method of Solid Phase Extraction (SPE)
      for the quantitative determination of a number of aristolochic acids (AAs) and
      aristololactams (ALs) in rat urine. METHOD: The HPLC peak area of AA-I , AA-II,
      AL-I and AL-II, and other sixteen AAs and ALs was chosen as evaluating index to
      study the extract results of five Solid Phase Extraction columns (Agilent C18/100
      mg, Alltech HG18/100 mg, Alltech C18/100 mg, Alltech C18/300 mg and Agilent
      Phenyl/200 mg) comparatively. The influences of two washing solvents (water and
      1% acetic acid-0.02% triethylamine solution) and seven eluting solvents (ether,
      acetone, chloroform, ethyl acetate, dichloromethane, methanol and acetonitrile)
      on extract results of AAs and ALs are comparatively studied with the extracting
      recoveries of AA-I , AA-II, AL-I and AL-II as indicators. The HPLC peak area of
      AA-I , AA-II, AL-I and AL-II, and other seven AAs and ALs with good separation
      being targets, several factors which affect extracting efficiency of analytes,
      including activating volume, cleansing volume, washing volume and eluting volume,
      are optimized by orthogonal design experiments with four factors at three levels.
      RESULT: The established method of SPE is as follows: Agilent Phenyl SPE column of
      200 mg, activating with 1.0 mL methanol, cleansing with 1 mL water, adding 1.0 mL
      rat urine sample, washing with 0.8 mL 1% acetic acid 0.02% triethylamine
      solution, and eluting with 3.0 mL methanol. CONCLUSION: The established method of
      SPE is efficient, selective, simple and fast, and can be used as urine
      pretreatment method to analyze a variety of aristolochic acids and
      aristololactams in rat urine.

PMID- 18338601
TI  - [Simultaneous determination of contents of sophoridine, oxymatrine and
      oxysophocarpine in seed of Sophora alopecuroides by HPLC].
AB  - OBJECTIVE: To develop a HPLC method for simultaneous determination of the
      contents of sophoridine, oxymatrine and oxysophocarpine in seed of Sophora
      alopecuroides. METHOD: Chromatographic condition included a Phenomenex Gemini C18
      (4.6 mm x 250 mm, 5 microm) column and thmobile phase consisting of a mixture of
      methanol-0.2% phosphatic acid (7:93). The detection wavelength was at 205 nm. The
      flow rate was 1.0 mL x min(-1) and column temperature was set at 30 degrees C.
      RESULT: All calibration curves showed good linearity (r > or = 0.9997) within
      test ranges. The mean recoveries were 100.0%, 97.0% and 97.0% respectively.
      CONCLUSION: This method is simple, rapid and accurate, and suitable for quality
      control of S. alopecuroides seed.

PMID- 18338602
TI  - [Effects of cordyceps sinensi on bleomycin-induced pulmonary fibrosis in mice].
AB  - OBJECTIVE: To study the prevention & treatment effect of cordyceps sinensi on
      bleomycin-induced pulmonary fibrosis (PF) in mice. METHOD: Rats were divided into
      4 groups. In BM group (model), pulmonary interstitial fibrosis model was
      established through nasal dripping of 5 mg x kg(-1) bleomycin. In PCT group
      (prevention & treatment with cordyceps sinensi), cordyceps sinensi was orally
      administered 48 h before bleomycin dripping. In CT group (treatment with
      cordyceps sinensi), cordyceps sinensi was orally administered at 14 d after
      bleomycin dripping, and NC group (normal mice, control). At 28 d, bronchoalveolar
      lavage fluid (BALF) and lung tissue were collected, right lung received HE
      staining and masson staining, the change in cell micro-structure was observed
      under electron microscope, the hydroxyproline (HYP) content in lung tissue of
      left lung was detected through acidolysis method, and TGF-beta1, IFN-gamma and IL
      4 concentration in BALF was detected through ELISA. RESULT: Compared with those
      in BM group, mouse lung coefficient decreased significantly (P < 0.05),
      alveolitis and fibrosis degree improved significantly in PCT and CT groups (P <
      0.05), HYP content in lung decreased (P < 0.05). TGF-beta1 and 1L-4 content in
      BALF decreased significantly in each drug intervention group, IFN-gamma content
      increased significantly (P < 0.05). CONCLUSION: The cordyceps sinensi can
      alleviate bleomycin-induced alveolitis and fibrosis degree in a certain degree.
      The mechanism of the alleviation is possibly due to its inhibition of TGF-beta1
      expression and its regulation of imbalance of the type I and II cytokine in lung
      tissue.

PMID- 18338603
TI  - [Experimental studies on treatment of depression with YJ-XCC1Z3 in mouse models].
AB  - OBJECTIVE: To evaluate the pre-clinical effect of YJ-XCC1Z3 on the treatment of
      depression with the mice mouse. METHOD: YJ-XCC1Z3 was administered at the dose of
      405 mg x kg(-1) and 135 mg x kg(-1) to observe the locomotor activity with the
      mouse locomotor activity recorder apparatus, to observe the effect of YJ-XCC1Z3
      on the duration of immohility in the mouse forced swimming test and tail
      suspension test, to observe the effect of YJ-XCC1Z3 on the body temperature and
      the metabolism of monoamine neurotransmitters in mouse brain in the mouse model
      of reserpine induced hypothermia, and to observe the effect of YJ-XCC1 Z3 on the
      times of 5-HTP induced head-twitches in mice. RESULT: There were no significant
      changes in the locomotor activity, but a significant reduction in the immobility
      time was observed in the mice treated with YJ-XCC1Z3 405 mg x kg(-1) and
      imipramine in the forced swimming test and the tail suspension test. YJ-XCC1Z3
      135 mg x kg(-1) and 405 mg x kg(-1) could improve the range of reserpine induced
      hypothermia in mice, and the latter could also enhance the times of 5-HTP induced
      head-twitches in mice. YJ-XCC1Z3 405 mg x kg(-1) and 135 mg x kg(-1) could
      increase the content of 5-HT and NE and decrease the ratio of 5-HIAA/5-HT in
      mouse brain, but the dose of 405 mg x kg(-1) could decrease the content of DA.
      The dose of 405 mg x kg(-1) could increase the content of 5-HIAA and had no
      obvious effect on the content of HVA and DOPAC. CONCLUSION: YJ-XCC1Z3 shows
      potent antidepressant effect by improving the behaviour of the mouse in
      depression and not inducing hyperlocomotion in the mice. This effect results in
      the increase of the content of 5-HT and NE in the mouse brain. YJ-XCC1Z3 can
      decrease the metabolism of 5-HT to effect the content of 5-HT.

PMID- 18338604
TI  - [Study on protective effects of Panax notoginseng saponins on doxorubicin-induced
      myocardial damage].
AB  - OBJECTIVE: To study the effects of Panax notoginseng saponins (PNS) on acute
      doxorubicin-induced myocardial injury in mice and the anti-tumor efficiency of
      doxorubicin. METHOD: Mice were given a dose of 15 mg x kg(-1) doxorubicin ip
      alone or in combination with 25, 50, 100 mg x kg(-1) PNS ig, 5 days before
      doxorubicin administration and following 3 days. Cardiotoxic effects were
      measured by serum levels of dehydrogenase (LDH), creatine kinase (CK) and
      creatine kinase isoenzyme (CK-MB) and activities of antioxidant enzymes in heart
      tissue. In vitro experiments were performed using embryonic rat heart cell H9C2
      to assess the protective effect of PNS (6.25-100 mg x L(-1)) against doxorubicin
      on cell viability. Anti-tumor efficiency of doxorubicin was evaluated by
      cytotoxic experiments using three cancer cell lines. RESULT: Pretreatment with
      PNS significantly lowered the levels of serum LDH, CK and CK-MB, and normalized
      myocardial superoxide dismutase, glutathione peroxidase and catalase activities.
      PNS also attenuated the inhibitory effect of doxorubicin on the viability of H9C2
      cells, but did not compromise its inhibitory effect on proliferation of cancer
      cells. CONCLUSION: PNS was demonstrated to attenuate doxorubicin-induced
      myocardial damage without compromising its anti-tumor activity.

PMID- 18338605
TI  - [Use W303-1A/hER-ERE-Lac Z to determine estrogenic compounds in traditional
      Chinese materia medica].
AB  - OBJECTIVE: To study the content of phytoestrogen in dissimilarity herbs. METHOD:
      The activity of phytoestrogen in heat-clearing drugs, drugs for relieving
      exterior syndrome, diuretic, anastaltics, tonics and astringents were detected
      based on the recombinant yeast cell (W303-1A/hER-ERE-Lac Z). The estrogenic
      activity in traditional Chinese materia medica were assayed quantitatively by
      determining the expression of beta-galactosidase. RESULT: The phytoestrogen
      concentration (6.35 x 10(-3) nmol x g(-1) E2 equivalent) in heat-clearing drugs
      was the highest while that in anastaltic and tonic drugs was the lowest, which
      was less than the detected limit. CONCLUSION: Compared with the other traditional
      Chinese materia medica, the content of phytoestrogen, which can bind to estrogen
      receptor, in giant knotweed rhizome, forsythia suspense, ash bark, baical
      skullcap root and ophiopogonis tuber were higher.

PMID- 18338606
TI  - [Effects on VEGF and VEGF mRNA expression in issues of callus in treating
      fracture of rabbit with three-period treatment theory of bone fracture in
      traditional Chinese medicine].
AB  - OBJECTIVE: To observe the effects of the three-period treatment theory of bone
      fracture in traditional Chinese medicine (TCM) on VEGF and VEGF mRNA expression
      in the issues of callus of rabbits. And to explore the rationality of phasing
      method in TCM in treating fracture. METHOD: one hundred and forty male and
      healthy rabbits were made 3 mm wide bone defection at lower one third part of
      both radius as fracture healing model. Then those rabbits were divided into four
      groups randomly, which are three-period treatment group (TTG), one-period
      treatment group (OTG), positive medicine treatment group (PTG) and model control
      group (MCG). Those rabbits in TTG were treated with three-period treatment. Those
      in OTG were treated with one-period treatment. Those in PTG were feed by
      guzhecuoshangsan, a Chinese patent medicine which is used to treat bone fracture.
      Those in model control group were given no prescription or drug but distilled
      water as same dose as that of other groups. At day 3, 6, 9, 14, 28, 42 and 56,
      five rabbits were selected from every group randomly and were killed by
      aeroembolism respectively. Their radius were taken out and the left one was taken
      as the research object. Immunohistochemistry stain and in situ hybridization
      stain were performed to examinate the VEGF and VEGF mRNA expression in the
      haematoma, fibrous callus and soft callus. RESULT: All TCM treatment groups can
      enhance the VEGF and VEGF mRNA expression in the haematoma, fibrous callus and
      soft callus at different time points in fracture healing. The VEGF and VEGF mRNA
      expression in the three issues of TTG had the tendency of higher than that of the
      other groups at the most time points after operation. CONCLUSION: TCM can promote
      the VEGF and VEGF mRNA expression in the haematoma, fibrous callus and soft
      callus. Different Chinese medicines play various roles on VEGF and VEGF mRNA
      expression at different stage of fracture healing. Treating fracture in three
      period treatment has more predominant effect on the expression of VEGF and VEGF
      mRNA in the haematoma, fibrous callus and soft callus than that of treating
      fracture with single prescription or drug. It is necessary to treat fracture in
      stages.

PMID- 18338607
TI  - [Protection of polysaccharide ATPS-2 from Armillariella tabescens on
      immunological liver injury in mice induced by BCG plus LPS].
AB  - OBJECTIVE: To observe the effect of polysaccharide ATPS-2 from Armillariella
      tabescens on the immunological liver injury in mice induced by BCG plus LPS.
      METHOD: BCG and LPS were adopted to establish BCG plus LPS liver injury model in
      mice. The content of serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST) and NO, the activity of superoxide dismutase (SOD) and
      malondiadehyde (MDA) content of liver homogenate in mice were measured by
      colorimetric method. The content of tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1 (IL-1), on serum were measured by enzyme linked immunosorbent assay
      (ELISA) , and T- and B-lymphocyte proliferation were measured by MTT. Index of
      liver, spleen and thymus were calculated after treatment. RESULT: Polysaccharide
      ATPS-2 from A. tabescens (25, 50, 100 mg x kg(-1)) could obviously reduce the
      high level of ALT, AST, NO and TNF-alpha, IL-1 on serum, inhibit the high level
      of MDA, increase the low activity of SOD in liver homogenate and enhance T-and B
      lymphocyte proliferation, elevate the spleen, thymic index and decrease liver
      index of the mice to different extent. CONCLUSION: Polysaccharide ATPS-2 from A.
      tabescens had apparently protective effects in the immunological liver injury
      mice induced by BCG plus LPS.

PMID- 18338608
TI  - [Method and meaning research on skin-test of four injections of traditional
      Chinese medicine].
AB  - Huangqi powder injection's positive rate of skin-test was 12.3%. Qingkailing
      powder injection was 3.0%. Qingkailing injection was 7.6%. Shuanghuanglian
      injection was 6.3%. Penicillin's rate of allergic reactions was 0.7%-10%.
      Different form of a drug (power or injection) and different drug consistency
      could influence the positive rate of skin-test. We don't use drug in positive
      group, and we use drug in negative group. Some trial subjects still happened
      allergic reactions in negative group of skin-test. In negative group of skin
      test, Huangqi power injection's rate of allergic reactions was 2.1%. Qingkailing
      injection was 0.4%. Shuanghuanglian injection was 0.9%-2.6%. Shuanghuanglian
      injection's rate of allergic reactions was 8.6% in all subjects (31/360 include
      the subjects with positive skin-test and allergic reactions). Qingkailing powder
      injection's rate of allergic reactions was 4.5% (6/132). Qingkailing injection' s
      rate of allergic reactions was 9.1% (12/132). Huangqi power injection's rate of
      allergic reactions was 15.4% (62/402). The total rate of allergic reactions was
      10.8%. The main appearance of Penicillin's skin-test was welling under skin, and
      with some blush. But the main appearance of traditional Chinese medicine skin
      test was blush, and with a little welling under skin. Skin-test can reduce the
      allergic reactions of Qingkailing powder injection, Shuanghuangiian injection,
      Huangqi power injection. It can be the one measure of reducing adverse reactions.

PMID- 18338609
TI  - [Studies on genetic diversity of medicinal Dendrobium by SRAP].
AB  - OBJECTIVE: To study the genetic diversity of medicinal Dendrobium by SRAP.
      METHOD: The genetic diversity of 9 spices Dendrobium was studied by using the
      optimized SRAP reaction system. The NTSYS software was used to analyze the
      markers. RESULT: Forty primer pairs were selected from 88 amplified 1 782
      polymorphic bands with an average of 44.55 polymorphic bands per primer pair.
      Cluster analysis using UPGMA method based on the data of SRAP amplified bands by
      40 primer pairs showed that 9 spices of could be distinguished into two main
      groups. Jaccard's similarity coefficient ranged from 0.330 2-0.789 2. CONCLUSION:
      The results of this research indicate that SRAP molecular marker is efficient to
      study the medical Dendrobium genetic diversity.

PMID- 18338610
TI  - [Comparative study on leaf ultrastructure in varieties of Chrysanthemum
      morifolium].
AB  - OBJECTIVE: To study leaf ultrastructure in varieties of Chrysanthemum morifolium.
      METHOD: The ultrastructure of leaves was observed through the transmission
      electron microscope. RESULT AND CONCLUSION: Chloroplast, mitochondria, starch
      grains and peroxide were observed in the ultrastructure of leaves, but the
      organelle, ultrastructure and their quantity showed differences in various
      cultivars. The results may explain, why hangju'has a better resistance to the
      adversity and is planted in large scale.

PMID- 18338611
TI  - [Study on total alkaloids content and its influential factors in medicinal
      materials of Tripterygium].
AB  - OBJECTIVE: To investigate the total alkaloids content profile and diversity of
      medicinal materials of Tripterygium. METHOD: The total alkaloids were extracted
      by organic solvent and purified by column chromatography (aluminium oxide), and
      determined by UV spectrometry. RESULT AND CONCLUSION: The total alkaloids content
      in phloem was 2 to 5 times richer than that in xylem, and their changes had shown
      concordance. For the different species/types, the content from high to low in
      order was T. hypoglaucum, Tripterygium F, T. wilfordii and T. regellii, but in
      each type, the disparity among different populations content was very small. The
      populations with higher content were in Suichuan, Jiangxi Province, Huangshan,
      Anhui Province, Jingning, Zhejiang Province and Kunming, Yuannan Province; which
      came from T. hypoglaucum and Tripterygium F. The degree of difference of total
      alkaloids content among individuals in each population was different. The
      populations, which had a rich content diversity, were in Jingning, Zhejiang
      Province, Taining, Fujian Province and Kunming, Yunnan Province. They will be
      used for good germplasm selecting. The thickness of medicinal materials did not
      affect the total alkaloids content in the same plant. The total alkaloids content
      in xylem changed with seasons: the highest in March, then declining from June to
      December, the lowest in December, While this did not happen in phloem.

PMID- 18338612
TI  - [Effect of water stress on growth and accumulation of active components of Isatis
      indigotica].
AB  - OBJECTIVE: To study the effect of water stress on the growth and accumulation of
      active components of Isatis indigotica. METHOD: By pot culture experiment,the
      characteristic indexes of water requirement, chlorophyll content, transpiration
      rate, photosynthesis, biomass and effective ingredient indirubin were studied
      under normal and water stress conditions, respectively. RESULT: With the increase
      of the extent and duration of water stress, the quantity of water requirement,
      chlorophyll content, respiration rate, photosynthesis and biomass of I.
      indigotica were decreased, while water use efficiency increased. CONCLUSION: It
      is a critical period of water requirement in July, high water content in soil and
      extreme water stress are not propitious to the accumulation of indirubin,
      appropriate water stress can stimulate indirubin accumulatio. The harvest of
      leaves of I. indigotica is optimal in July, while the harvest of root is
      appropriate in October. Yield and quantity of I. indigotica are improved when the
      field capacity is between 45% and 70%.

PMID- 18338613
TI  - [Study on release mechanism of berberine hydrochloride-loaded carboxymethyl
      konjac glucomannan pellets for colonic delivery].
AB  - OBJECTIVE: To study release mechanism of berberine hydrochloride (BH) from
      carboxymethyl konjac glucomannan pellets for colonic delivery. METHOD: The
      pellets were prepared by ionotropic gelation technique. The effects of the kinds
      of enzyme and enzyme concentration of dissolution media on the release of BH and
      the erosion properties of the pellets were studied. RESULT: Compared with the
      dissolution media without enzymes, the release of BH and the erosion of the
      pellets were increased obviously in the media with rat cecal and colonic content
      or beta-mannase, the degradation of the carrier material of pellets by enzymes
      was the main factor which result in the erosion of the pellets. With the
      increased of beta-mannase concentration, the release of BH and the erosion of the
      pellets increased, the amount relationships of the release of BH and the erosion
      of the pellets were approximately 1:1. The release of BH exhibit Peppas equation,
      the n value was more than 1. CONCLUSION: The release mechanism of BH from the
      pellets was enzymatic erosion-controlled, which indicates the potential of the
      pellets to serve as a colon-specific drug delivery system.

PMID- 18338614
TI  - [Study on preparation of ampelopsin liposomes].
AB  - OBJECTIVE: To study the formulation and preparation of ampelopsin liposomes and
      evaluate their quality. METHOD: The liposomes were prepared by a film-ultrasonic
      dispersion technique. Served as quota with the entrapment ratio and appearance
      and diameter of the liposomes, the optimal formulation and preparation were
      selected by means of an uniform design test. The appearance of liposomes was
      observed by micrography. The diameter and electric charge of surface were
      determined by granularity mensuration instrument. The entrapment ratio and the
      leakage rate of ampelopsin liposome were determined by means of dialyze. The
      content of ampelopsin was determined by UV. RESULT: The result of electron
      micrography and the size distribution showed that the liposomes were similar to
      spherical small unilamellar vesicles. The mean diameter was (258.2 +/- 51.2) nm
      and the electric charge of surface is 19.0 mV. The entrapment ratio of ampelopsin
      liposomes was 62. 3% and the lecithoid oxidative rate was 0.83% (n = 3).
      CONCLUSION: The selected formulation and preparation of ampelopsin liposomes is
      efficient and practicable.

PMID- 18338615
TI  - [Study on preparation of phenols gastric floating tablet].
AB  - OBJECTIVE: To study the preparation of phenols gastric floating tablet. METHOD:
      The tablets which were prepared using Eudragit IV, HPMC(K4M), MCC101 and
      Octadecanol as excipients were evaluated by vitro floatation and releasing
      performance. The pressure of preparationg was also study to select the optimal
      preparation. RESULT: The tablets were successfully prepared in which the drug,
      Eudragit IV, Octadecanol were 31% respectively,and MCC101 was 7%. And 3-4 kg was
      found to be the eligible pressure. CONCLUSION: The study was found to be
      effective in the process of phenols gastric floating tablet.

PMID- 18338616
TI  - [Studies on absorption kinetics of paeonol and paeonol-beta-CD in rat's
      intestines].
AB  - To explore the absorption mechanism of paeonol-beta-CD from various intestinal
      segments and offer biopharmaceutics data for paeonol new dosage form. The
      absorption kinetics and permeability rate consatants were investigated by the in
      situ perfusing method in rats. The absorption of the drug conforms to the firt
      order kinetics and passive transport mechanism . The results indicate that
      paeonol-beta-CD absorption mechanism wasn't change.

PMID- 18338617
TI  - [Triterpenoid saponins from flower bud of Jasminum officinale var. grandiflorum].
AB  - OBJECTIVE: To study the chemical constituent bud of the flowers of Jasminum
      officinale var. grandiflorum. METHOD: The compounds were isolated and purified by
      recrystallization and chromatography on silica gel and Sephadex LH - 20 column.
      Their structures were elucidated on the basis of physicochemical properties and
      spectral analysis. RESULT: Six triterpenoid saponins were identified as 3-O-alpha
      L-rhamnopyranosyl (1 --> 2)-beta-D-xylopyranosyl- hederagenin-28-O-beta-D
      galactopyranosyl (1 --> 6)-beta-D-galactopyranosyl ester (1), hederagenin-3-O
      beta-D-glucopyranosyl (1 --> 3)-alpha-L-arabinopyranoside (2), 2alpha, 3beta, 23
      trihydroxyolean-12-en-28-oic-O-beta-D-glucopyranosyl ester (3), hederagenin-3-O
      beta-D-xylopyranosyl (1 --> 3)-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L
      arabinopyranoside (4), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-oic-O-alpha-L
      rhamnopyranosyl (1 --> 4)-beta-D-glucopyranosyl (1 --> 6)-beta-D-glucopyranosyl
      ester (5), hederagenin-3-O-alpha-L-rhamnopyranosyl (1 --> 2)-alpha-L
      arabinopyranoside (6). CONCLUSION: Compound 1 is a new compound. Compounds 2, 3,
      4, 5, 6 were isolated from the genus Jasminum for the first time.

PMID- 18338618
TI  - [Studies on chemical constituents from roots of Mirabilis jalapa].
AB  - OBJECTIVE: To investigate the anti-HIV constituents from the root of Mirabilis
      jalapa. METHOD: The compounds were isolated by column chromatography on silica
      gel, Sephadex LH - 20, MCI-gel CHP-20P and RP-18. The structure were identified
      by means of NMR and MS analyses (1H-NMR, 13C-NMR, MS). RESULT: Eleven compounds
      were isolated and identified as astragaloside II (1), astragaloside II (2),
      astragaloside IV (3), astragaloside VI (4), flazin (5), 4'-hydroxy-2, 3
      dihydroflavone 7-beta-D-glucopyranoside (6), gingerglycolipid A (7), 3, 4
      dihydroxybenzaldehyd (8), p-hydroxybenzaldehyde (9), beta-sitosterol (10) and
      daucosterol (11). CONCLUSION: Compounds 1-9 were obtained from this genus for the
      first time.

PMID- 18338619
TI  - [Comparison of kinetic behavior in both plasma and tissue after intravenous
      administration of alpha-asarone in lipid emulsion and aqueous solution in rats
      and mice].
AB  - OBJECTIVE: To compare the pharmacokinetics and tissue distribution of alpha
      asarone in lipid emulsion and aqueous solution for injection and study the
      feasibility of lipid emulsion of alpha-asarone as the parenteral drug delivery
      system. METHOD: HPLC was used to determine the drug concentration in rat plasma
      and mice tissues after intravenous (i.v.) administration of lipid emulsion and
      aqueous solution of alpha-asarone at a single dose (40 mg x kg(-1)),
      respectively. RESULT: The plasma concentration-time profiles of lipid emulsion
      and aqueous solution of alpha-asarone after intravenous administration of them
      are similar and the drug concentration-time data were fitted to a two-compartment
      open model. The results of tissues distribution showed that distribution contents
      of alpha-asarone from lipid emulsion and aqueous solution in vivo are similar in
      lungs but lipid emulsion increased the uptake in livers and spleens, and
      decreased the uptake in hearts and kidneys for alpha-asarone. CONCLUSION: The
      plasma concentration-time profiles of alpha-asarone in lipid emulsion and aqueous
      solution are similar, but lipid emulsion significantly altered the tissue
      distribution of alpha-asarone, which may be beneficial to decrease its potential
      toxicity to heart and kidney.

PMID- 18338620
TI  - [HPLC fingerprints in seed of Celosia argentea].
AB  - For preferable authentication and regulation of material quality of Celosia
      argentea, HPLC fingerprints of different habitats were studied. Analysis was
      carried out on a Hypersil ODS2 column (4.6 mm x 250 mm, 5 microm) with
      acetonitrile-0.1% glacial acetic acid as the mobile phase, and eluates were
      detected by an evaporative light scattering detector (ELSD). The similarity
      evaluation system for chromatographic fingerprint of traditional Chinese medicine
      ( Version 2004 A) was applied to analyses the similarity of the fingerprint of
      diverse habitats. The similarity results were verified by SPSS. The
      chromatographic profiles of the samples from different regions were very similar.
      HPLC fingerprints of Semen C. argentea 12 common peaks and each peak in the
      fingerprint was well separated under the chromatographic condition above. The
      different habitats of C. argentea can be grouped to two types: the middle region
      and the south region. The chemical constituents of C. argentea vary with
      different habitats so selection of material habitat is very important for quality
      control of C. argentea. The fingerprint with high individuality and specificity
      could be applied in the identification and quality control of the material of C.
      argentea.

PMID- 18338621
TI  - [Realgar nanometer suspension inducing apoptosis of Siha cell and its effect on
      expression of HPVE6/E7 oncogene].
AB  - OBJECTIVE: To study the growth-inhibitory and apoptosis-inducing effects of
      realgar nanometer suspension in human carcinoma cervical cell Siha line, and the
      effect on HPV16E6/E7 oncogene expression. METHOD: A " micro-jet efflux" strategy
      was used for the preparation of realgar nanometer suspension. Siha cells were
      treated with various concentrations (6.25, 12.5, 25, 50 mg x L(-1)) of realgar
      nanometer suspension for different hours (12, 24, 48, 72 h). The effect of
      realgar nanometer suspension on Siha cell growth suppression was detected by MTT
      method. Special morphological changes of apoptosis were observed by light and
      transmission electron microscopy (TEM) and DNA fragments electrophoresis. The
      apoptotic rates were quantified by flow cytometry (FCM). The expression of
      HPV16E6/E7 mRNA was assayed by RT-PCR. RESULT: After being treated with 25-50 mg
      x L(-1) realgar nanometer suspension for 48, 72 h, the survival of Siha cells
      decreased, and the rate of apoptosis markedly increased. With TEM and DNA
      electrophoresis, the special morphological changes were found. The apoptotic
      rates of Siha cells treated with realgar nanometer suspension were significantly
      higher than those in the control group (P < 0.01). G0-G1 phase arrest appeared
      following the treatment with realgar nanometer suspension in 25 and 50 mg x L(-1)
      48 h. RT-PCR assay revealed that realgar nanometer suspension reduced HPV16E6/E7
      gene expression. CONCLUSION: Realgar nanometer suspension can inhibit the
      proliferation of human carcinoma cervical cell Siha line and induce the cell
      apoptosis. The mechanism may be related to the down-regulation of HPV16E6/E7
      oncogene expression.

PMID- 18338622
TI  - [Research on phytoestrogenic effects and its mechanism of psoralen].
AB  - OBJECTIVE: To observe and evaluate the phytoestrogenic effects and its mechanism
      of psoralen in estrogen receptor (ER) alpha and beta positive T47D and ishikawa
      cells. METHOD: The proliferation rate of T47D influenced by 1 x 10(-5) mol x L(
      1) to 1 x 10(-9) mol x L(-1) psoralen and that of Ishikawa influenced by 1 x 10(
      6) mol x L(-1) and 1 x 10(-7) mol x L(-1) psoralen were analyzed by MTT assay. PR
      mRNA expression in T47D was quantified by RT-PCR assay. Estrogen receptor
      antagonist ICI 182, 780 was employed as a tool. ER-alpha and ER-beta expression
      of T47D was measured by flow cytometry. RESULT: The proliferation rates of T47D
      cells treated with 1 x 10(-5) mol x L(-1) to 1 x 10(-7) mol x L(-1) psoralen and
      ishikawa cells treated with 1 x 10(-6) mol x L(-1) to 1 x 10(-7) mol x L(-1)
      psoralen were increased significantly. The RT-PCR result showed that 1 x 10(-7)
      mol x L(-1) and 1 x 10(-6) mol x L(-1) psoralen could increase PR expression in
      T47D cells. The above effects could be blocked by ICI 182,780. Psoralen could
      also induce the augment of ER-alpha and ER-beta expression in T47D cells
      significantly. CONCLUSION: Psoralen has phytoestrogenic effects. The effects are
      attained through ER pathway.

PMID- 18338623
TI  - [Inhibitory effects of emodin on proliferation of rat vascular smooth muscle cell
      induced by angiotensin II].
AB  - OBJECTIVE: To investigate the effects of emodin on the proliferation of cultured
      rat vascular smooth muscle cell (VSMC) induced by angiotensin II. METHOD: VSMCs
      were cultured by explant method. Cell proliferation model was established by
      stimulation with Ang II. Cell proliferation was measured by MTT assay to observe
      the effects of emodin (10, 20, 40 and 80 micromol x L(-1)) and N(G)-nitro-L
      arginine methyl ester (L-NAME, 100 micromol x L(-1)) on VSMC proliferation
      induced by Ang II. The expression of PCNA was measured by immunohistochemical
      staining. Nitric oxide (NO) level was measured by Griess reagent. Nitric oxide
      synthase (NOS) and inducible nitric oxide synthase (iNOS) levels were detected by
      chemical colorimetric method. mRNA expression of iNOS was measured by reverse
      transcription polymerase chain reaction (RT-PCR). RESULT: Emodin at the doses
      range from 10 to 80 mol x L(-1) inhibited cell proliferation in a dose and time
      dependent manner. The inhibitory effects were partly blocked by 100 mol x L(-1)
      of L-NAME. Emodin markedly decreased the expression of PCNA in VSMC, increased
      NO, NOS and iNOS levels, and increased iNOS mRNA expression in VSMC. CONCLUSION:
      Emodin could inhibite VSMCs proliferation induced by Ang II. Inhibiting the
      expression of PCNA, increasing the NO secretion and upregulating the iNOS gene
      expression might be associated with the inhibitory effects.

PMID- 18338624
TI  - [Effect of compound Rhizoma Coptidis capsule on expression of transforming growth
      factor-beta1 and type IV collagen proteins in renal tissue of diabetic rats with
      nephropathy].
AB  - OBJECTIVE: To explore the effect and mechanism of compound Rhizoma Coptidis
      capsule (CRCC) on diabetic nephropathy in experimental rats. METHOD: The rat
      model of early diabetic nephropathy was induced by injection of streptozotocin
      (STZ). The rats were divided into 6 groups: normal control group, model group, 3
      CRCC treatment groups and XKW treatment group. The fasting blood glucose (FBG),
      blood urea nitrogen (BUN), creatinine (Cr), insulin (Ins) and urinary protein
      (Upro) were tested 30 days later. The expression of transforming growth factor
      beta1 (TGF-beta1) and type IV collagen (IV-C) proteins and the pathological
      changes in renal tissue of diabetic rats with nephropathy were observed by
      optical micrography. RESULT: CRCC could reduce the levels of FBG, BUN, Cr, Upro
      and the expression of TGF-beta1 and IV-C proteins, and alleviate pathological
      lesion in renal tissue of diabetic rats with nephropathy. CONCLUSION: CRCC may
      protect the renal function and slow down the progression of diabetic nephropathy
      in rats by suppressing the expression of TGF-beta1 and IV-C proteins in renal
      tissue.

PMID- 18338625
TI  - [Study on changes of protein phosphorylation of p65, IkappaBalpha and
      IkappaBepsilon in lymphocytes of rats in progress of aging and interventional
      effect of Epimedium flavonoids].
AB  - OBJECTIVE: To study the characteristics of protein phosphorylation of p65,
      IkappaBalpha and IkappaBepsilon in lymphocytes of rats in the progress of aging
      and the the interventional effect of Epimedium flavonoids (EF). METHOD: We chose
      the lymphocytes derived from SD rat spleen. We divided the SD rats into five
      groups i. e. 4 months (4 m), 27 months (27 m), the 27 m EF treated group (27 m +
      EF), and we also observed the whole interventional effect of PDTC (a NF-kappaB
      inhibitor) on old rat groups (27 m PDTC, 27 m PDTC + EF ) when IkappaBepsilon,
      IkappaBalpha were detected. Through the western-blotting analyses, we studied the
      entire characteristics and distinctions of phosphorylation expression in
      molecules related to NF-kappaB signal transduction pathway p65, IkappaBepsilon
      and IkappaBalpha in lymphocytes across the age spectrum of rats in aging. We also
      observed the whole interventional effect of EF on lymphocytes of old rats.
      RESULT: With the increasing of age, the mean level of phosphorylation expressions
      of p65, IkappaBalpha and IkappaBepsilon in rat spleen lymphocytes decreased
      obviously, When inhibited NF-kappaB by PDTC, there was decreased evidently, while
      PDTC + EF can active NF-kappaB family and the above molecules were increased to a
      certain extent. CONCLUSION: The phosphorylation expressions of p65, IkappaBalpha
      and IkappaBepsilon in rat spleen lymphocytes were not enouphe, EF have a strong
      effect to upregulated the expression of them during aging.

PMID- 18338626
TI  - [Effect of Qiangxin Fumai granule on myocyte apoptosis of sinus node and Bax, Bcl
      2, Fas-L gene protein in rabbits of sinoatrial ischemia/reperfusion].
AB  - OBJECTIVE: To explore the molecular mechanism of Qiangxin Fumai granule (QFG, an
      effective Chinese composite drug) in preventing and treating sick sinus syndrome
      (SSS). METHOD: Rabbit model of sinoatrial ischemia/reperfusion was established by
      occluding and loosening the root of right coronary artery. Effect of QFG on cell
      apoptosis was observed by TUNEL method, and its effect on apoptotic related gene
      Bax, Bcl-2 and Fas-L gene protein expression was observed by immunohistochemical
      method. Average light density values of the expression of Bax, Bcl-2 and Fas-L of
      SAN cells was determined by Imagepro Plus image analysis system. RESULT:
      Sinoatrial injury induced by ischemia/reperfusion could cause evident sinoatrial
      cell apoptosis, enhance Fas-L gene protein expression and obviously enhance Bax
      gene protein expression, reduce Bcl-2/Bax ratio. QFG could significantly down
      regulate Fas-L and Bax gene protein expression, up-regulate Bcl-2/Bax ratio,
      significantly inhibit and block the sinoatrial cell apoptosis. CONCLUSION: To
      inhibit and block the event of cell apoptosis through regulating Bax, Bcl-2 and
      Fas-L gene protein expression in sinoatrial node after ischemia/reperfusion might
      be one of the mechanisms of QFG in preventing and treating sinoatrial
      ischemia/reperfusion injury of SSS.

PMID- 18338627
TI  - [Effects of immunotherapy with infantile recurrent respiratory tract infection by
      Chinese materia medica].
AB  - OBJECTIVE: To explore the effect of Chinese materia medica on immune intervention
      of infantile recurrent respiratory tract infection. METHOD: Thirty-one children
      of recurrent respiratory tract infection were randomly divided into two groups:
      therapy group was treated with oral Chinese materia medica (b. i. d), control
      group was only treated with oral carboxymethyl liquor (< 4 years, 3 mL; 4-7
      years, 5 mL; > 7 years, 7 mL, t. i. d). The change of IL-12,TNF-alpha, IL-6, IL
      13, IL-6 and IL-4 in different time were observed and analyzes. RESULT: Compared
      with the control group, the level of IL-12 and IL-2 was significantly increased
      after treatment of oral Chinese materia medica (P < 0.01), however, the level of
      TNF-alpha, IL-13, IL-4, and IL-6 was decreased after treatment (P < 0.01). During
      one years follow-up study, the frequency of respiratory infection every year of
      therapy group was significantly decreased than that of control group. CONCLUSION:
      Chinese materia medica could prevent infantile recurrent respiratory tract
      infection effectively, increase humoral immunity function and ensure normal
      growth in children.

PMID- 18338628
TI  - [Herbal CONSORT statement and standardization of reporting traditional Chinese
      drug trials].
AB  - Based on detailed explanation of the herbal CONSORT statement, and the
      consideration of the character of traditional Chinese drugs, to discuss the
      standardization of reporting traditional Chinese drug trials. The standards of
      reporting traditional Chinese drug trials are not consolidated yet. In the year
      2006, Reporting Randomized, Controlled Trials of Herbal Interventions: An
      Elaborated CONSORT Statement was developed by the CONSORT group and published.
      This herbal CONSORT statement includes 5 parts, and totally 22 items, in which
      the items of participant criteria, intervention, control setting and outcomes, et
      al. are elaborated to be adaptable to herbal intervention trials. This herbal
      CONSORT statement has provided valuable basis for the development of standards of
      reporting traditional Chinese drug trials, though it is not completely adaptive
      to be the reporting standards in consideration of the background theory and the
      animal drugs and mineral drugs that traditional Chinese drugs contain. The proper
      reporting standards of traditional Chinese drug trials should take the different
      types of drugs and the different purposes of trials into consideration. The trial
      reports of drugs that must be applied under the instruction of traditional
      Chinese medicine (TCM) theory should report participant criteria that include TCM
      syndrome differentiation and other important characters of TCM interventions.

PMID- 18338629
TI  - [Reviews on antiviral activity of chemical constituents from plants].
AB  - This paper reviewed the progress in researches on antiviral activity of chemical
      constituents from plants in recent years, the antiviral activity and mechanism of
      action of flavonoids, alkaloids, terpenoids, coumarins and polysaccharoses were
      sammarszed, provided new leading compound for antivirus new drugs from the plares
      in prospect.

PMID- 18338630
TI  - [Advances in research on drug release mechanisms and modes of thermosensitive
      gel].
AB  - Thermosensitive gel with the property of LCST (Lower Critical Solution
      Temperature) was studied as a hot spot these years for it can be used as one
      supportor of drug controlled release system which can release drug at right
      point, right time and right quantity. With further reseaches and applications of
      thermosensitive gel, the modes and mechanisms of it were discovered and poited
      out, drug release models were also established step by step. Resesrches on drug
      release mechanisms and modes of thermosensitive gel will make it applied better
      in fields of medicine and biology.

PMID- 18338631
TI  - [Recent progress on pharmacological effects of Gastrodia elata].
AB  - In the present review, English literature on the pharmacological effects of
      Gastrodia elata was summarized. The literature mainly reported the effects of G.
      elata on central nervous system, including anticonvulsant, neuroprotection,
      improvement on learning and memory, and so on. These pharmacological effects were
      closely associated with its phenolic components.

PMID- 18338632
TI  - [A new target for diabetes therapy: advances in the research of glycogen synthase
      kinase-3 inhibitors].
AB  - Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase, originally
      identified as a protein kinase by its ability to phosphorylate and inactivate
      glycogen synthase. It was found that the overexpression of GSK-3 is associated
      with some diseases, such as diabetes, Alzheimer disease and other
      neurodegenerative diseases. Some pharmacological inhibitors of GSK-3 have been
      demonstrated to mimic insulin signaling, adjust glycogen synthesis and glucose
      metabolism, and improve insulin resistance. So GSK-3 inhibitors are realized as a
      new approach of treating diabetes. This review summarizes current advances in
      research of GSK-3 inhibitors as a new therapeutic approach for diabetes.

PMID- 18338633
TI  - [Progress in the design of selective ATP-competitive kinase inhibitors].
AB  - Kinases play crucial roles in the life of cell. Their functional abnormity
      usually leads to many human major diseases including tumors. The prospecting of
      ATP-competitive small-molecule kinase inhibitors targeting kinases of therapeutic
      interest has become the focus of researches. Due to the high conservation of the
      catalytic domain of kinases, the selectivity of kinase inhibitors is poor in
      general. However, along with the development of structural biology and computer
      aided drug design, great progress in the research of selective, ATP-competitive
      kinase inhibitors has been achieved in recent years. In this account, the review
      has been made on the development of the design of selective kinase inhibitors.

PMID- 18338634
TI  - [Regulations of residual solvents in pharmaceuticals and advances in the research
      of its analytical methods].
AB  - If the presence of residual solvents in pharmaceuticals exceeds tolerance limits
      as suggested by safety data, they may be harmful to the human body or the
      environment. It is because of this that the determination of residual solvents
      receives a great deal of attention. This paper reviews in detail the changes in
      the regulations on residual solvents in pharmaceuticals in leading
      pharmacopoeias, and the advances in the techniques involved, especially, the
      recent advances in the analytical techniques are summarized. At the end, the
      authors introduce the prospect of the expert system for determining residual
      solvents in pharmaceuticals based on the studies of their research group.

PMID- 18338635
TI  - Effect of berberine on PPARalpha/delta/gamma expression in type 2 diabetic rat
      retinae.
AB  - Retinopathy is a major cause of morbidity in diabetes and remains the primary
      cause of new blindness. Therefore, it is necessary to find new drug to treat
      diabetic retinopathy. Type 2 diabetes mellitus (T2DM) rats were induced by
      injection (ip) with streptozotocin (STZ) 35 mg x kg(-1) and fed with a high
      carbohydrate/high-fat diet 2 weeks later. From week 17 to 32, diabetic rats were
      given different doses of berberine 75, 150, and 300 mg x kg(-1), fenofibrate 100
      mg x kg(-1) and rosiglitazone 4 mg x kg(-1), separately. Retinal structure was
      observed with hematoxylin-eosin staining and peroxisome proliferator-activated
      receptors (PPARs) alpha/delta/gamma protein expressions were detected by
      immunohistochemistry. The retina of control rats was thicker than that of other
      groups, 16 weeks treatment with berberine (150 and 300 mg x kg(-1)) and
      rosiglitazone 4 mg x kg(-1) thickened the diabetic retina, but no difference
      existed in retinal structure among groups. Both berberine (150 and 300 mg x kg(
      1)) and rosiglitazone 4 mg x kg(-1) significantly decreased PPARy expression in
      diabetic retina; while berberine (150 and 300 mg x kg(-1)) and fenofibrate 100 mg
      x kg(-1) obviously increased both PPARalpha and PPARdelta expressions in diabetic
      retina. Berberine modulates PPARalpha/delta/gamma protein levels in diabetic
      retina which may contribute to ameliorate retinopathy complication induced by STZ
      and a high-carbohydrate/high-fat diet. It is expected that berberine might be a
      more beneficial drug to treat diabetic retinal complication comparing with
      fenofibrate and rosiglitazone.

PMID- 18338636
TI  - [Effect of salvianolic acid B on brain energy metabolism and hydrocephalus of
      cerebral ischemia in mice at different time].
AB  - Mice pathological model of acute cerebral ischemia was established. In order to
      observe the effect of salvianolic acid B (Sal B) on brain energy metabolism and
      hydrocephalus in the brain of mice at different ischemic times, the energy charge
      (EC), content of phosphocreatine (PCr), level of lactic acid (Lac), activity of
      Na+ -K+ -ATPase, brain index and water content of brain were measured at 6, 12,
      18, 24, and 30 min, separately after ligating bilateral common carotid arteries
      in mice. NIH mice were randomly divided into sham-operated group (sham), cerebral
      ischemia group (ischemia), Sal B-treated group (Sal B) and nimodipine-collated
      group (Nim). At 6 min after cerebral ischemia, EC, content of PCr and activity of
      Na +-K -ATPase began to decrease, while level of Lac, brain index and water
      content of brain increased gradually. However, Sal B (22.5 mg x kg(-1) improved
      pathophysiological changes at different ischemic times. Especially at 30 min
      after cerebral ischemia in Sal B group, EC (P < 0.01), content of PCr (P < 0.01
      and activity of Na+ -K+ -ATPase ( < 0.05) increased significantly. Meanwhile,
      level of Lac (P < 0.01, brain index (P < 0.01) and water content of brain (P <
      0.05) were lower obviously than those of cerebral ischemia group. Sal B could
      alleviate hydrocephalus by the improvement of energy metabolism in mice with
      acute cerebral ischemia, that provides scientific evidence that Sal B can be used
      for the clinical application of ischemic diseases.

PMID- 18338637
TI  - [Effect of Bax translocation on TNFalpha induced apoptosis of human breast cancer
      MCF7 cells stably expressed hGFP-Bax].
AB  - Established human breast cancer MCF7 cell line stably expressed GFP-Bax, which
      was used to investigate Bax translocation from cytosol into mitochondria induced
      by TNFalpha. Bax translocation from cytosol into mitochondria and DNA
      fragmentation were investigated under fluorescence microscope. The viability of
      cells treated with TNFalpha was measured by MTT method. Immunofluoresence method
      was used to investigate Bax translocation to mitochondria and Cyt-c release from
      mitochondria. The Dose-effect and time-course relationship were also observed and
      calculated by the percentage of GFP-Bax punctate cells. The TMRE assay was used
      to investigate the function of mitochondria. The results showed that Bax
      translocation from cytosol into mitochondria was associated with apoptosis
      induced by TNFalpha in hGFP-Bax-tagged MCF7 stable cell line.

PMID- 18338638
TI  - [Apoptosis-inducing effect of alternol on mouse lymphocyte leukemia cells and its
      mechanism].
AB  - Alternol is purified from fermentation productions of microorganisms named as
      Alternaria alternata var. monosporus. The research is to investigate the
      apoptosis-inducing effect of alternol on mouse lymphocyte leukemia (L1210) cells
      and the possible mechanisms. MTT method was used to evaluate the viability of
      L1210 cells. Apoptosis of L1210 cells was detected by morphological assessment,
      DNA electrophoresis assay and flow cytometry. Western blotting analysis was
      carried out to determine the apoptosis-related proteins. Proliferation inhibition
      of L1210 cells by alternol was found remarkably in a dose-dependent manner. When
      treated with alternol, apoptotic morphological features of L1210 cells were
      observed by fluorescent microscopy (AO/EB) and the apoptosis rate was also
      elevated in a time-dependent manner. After treatments with various concentrations
      of alternol for 48 h, DNA laddering appeared. The increase of reactive oxygen
      species (ROS) production was found after cells were exposed to alternol for 6 h,
      while the decrease of mitochondrial transmembrane potential (delta psi m) was not
      found until cells were exposed to alternol for 24 h. Furthermore, the level of
      Bcel-2 and Bcl-2/Bax was down-regulated, while the level of caspase-3 and caspase
      9 but not caspase-8 was up-regulated when alternol was added for 72 h. In
      summary, the results suggested that alternol could inhibit the proliferation of
      L1210 cells and induce apoptosis of L1210 cells, which was mediated by
      mitochondria-dependent pathway.

PMID- 18338639
TI  - [Effect of recombinant microplasmin on acute cerebral infarction in rats].
AB  - The effect of recombinant microplasmin (micro-plasmin) on acute cerebral
      infarction was evaluated in rats, and compared with recombinant tissue
      plasminogen activator (rt-PA). After the model of middle cerebral artery
      occlusion (MCAO) was established by autologous blood clots, different doses of
      micro-plasmin (2.5, 5, and 10 mg x kg(-1)) were administered into the thrombus
      intra-arterial. Twelve hours after administration of micro-plasmin, the
      neurological deficit score of rats was recorded and the infarct volumes were
      determined. Bleeding time (BT), fibrin degradation product (FDP) concentration in
      serum and thrombin time (TT), prothrombin time (PT) and fibrinogen (FIB)
      concentration in plasma were tested after administration. Intra-arterial
      administration of micro-plasmin could reduce significantly neurological deficit
      score and infarct volumes in MCAO rats. FDP concentration increased significantly
      as compared with model group. There were no significant differences in TT, PT and
      BT. FIB concentration reduced markedly as compared with model group, but had no
      significant difference as compared with sham group. The results suggest that
      micro-plasmin is effective in treatment of rat acute cerebral infarction, and has
      no significant influence on fibrinolytic system and blood clotting system,
      indicating that micro-plasmin may be useful for treatment of acute cerebral
      infarction, and not lead to hemorrhage. Micro-plasmin seems to be distinguished
      from clinical used rt-PA by its no hemorrhage effect.

PMID- 18338640
TI  - [Design, synthesis and activity evaluation of novel matrix metalloproteinases
      inhibitors based on the structure of enzyme].
AB  - A novel inhibitor series for matrix metalloproteinases (MMPs) were designed and
      synthesized. Using succinate and malonate as zinc binding groups and long
      hydrophobic substituents to bind with S1' pockets, the compounds showed
      micromolar inhibition and selectivity for MMP-2 over others. And we found a
      better activity compound. It is a chance to find a better precursor of MMP-2
      inhibitors with activity and bioavailability by further optimization of
      compounds.

PMID- 18338641
TI  - Isolation and activity of an alpha-amylase inhibitor from white kidney beans.
AB  - An alpha-amylase inhibitor (alpha-AI) was isolated from white kidney beans
      (Phaseolus vulgaris L) by ethanol fractional precipitation, ion exchange
      chromatography and gel filtration column chromatography. It was a homogeneity
      glycoprotein demonstrated by SDS-PAGE and gel filtration on CL-6B. The
      glycoprotein contained 88.2% protein and was rich in aspartic acid, glutamic
      acid, leucine, threonine and serine. The carbohydrate moiety was consisted of
      Man, Glc, Gal and Xyl in a mole ratio of 2.42: 1.50: 1.52: 1.00. The glycan and
      the core protein backbone was connected by O-linkage as determined by beta
      elimination reaction. The continuous oral administration of the alpha-AI (150 mg
      x kg(-1) x d(-1)) for 7 days can lower fasting blood glucose and 300 mg x kg(-1)
      x d(-1) alpha-AI for 7 days can improve the sugar tolerance on alloxan-dependent
      diabetic model rats. The result showed the alpha-AI obtained from white kidney
      beans had good hypoglycemic effect on alloxan induced diabetic rats and may have
      high potential pharmaceutical value as a regulative digestive-starch degradation
      in patients suffering from diabetes.

PMID- 18338642
TI  - Two new flavones from Rubus biflorus Buch.
AB  - This project is to study chemical constituents of Rubus biflorus Buch (Chinese
      name "Fenzhimei"), isolated by silica gel chromatography and structure determined
      by spectroscopic techniques. Two flavones were isolated from Rubus biflorus Buch
      and identified as 8-methyl-6-(3"-methylbut-2"-enyl)-5, 7-dihydroxy-5'-methoxy-3',
      4'-methylenedioxy flavone (A) and 8-methyl-5-methoxy-6,7-(2", 2"-dimethylpyran)
      3', 4'-methylenedioxy-5'-(3'''-methylbut-2'''-enyl) flavone (B), named as
      fenzhimines A and B, respectively. Compounds A and B are two new flavonoids.

PMID- 18338643
TI  - [Identification of related substances in rifampicin by HPLC-DAD spectroscopy
      correlation].
AB  - A qualitative analysis method to identify related substances of rifampicin by
      correlation of spectra in chromatography was established. Standard
      chromatographic and spectral data obtained by high-performance liquid
      chromatography with diode array detection (HPLC-DAD) were developed and used in
      identification of peaks in samples by calculating correlation coefficients (R).
      The comparison of spectra was expanded to three-dimensional space. Peaks in
      chromatography can be identified accurately and rapidly through chromatographic
      system change. The identification results were validated by LC-MS. The threshold
      of R was set to 0.99 in order to discriminate the impurities and the minimal
      amount for identification was 30 ng. Taking full advantage of chromatographic
      separate efficiency and spectral exclusiveness, the method is accurate and
      reproducible as a new and effective way to identify multi-components in drugs.

PMID- 18338644
TI  - [Interaction between (E)-2-(4-(diethylamino methyl) benzylidene)-5,6-dimethoxy
      2,3-dihydroinden-one and P-glycoprotein].
AB  - Cell lines of Bcap37 and Bcap37/MDR1 (the high P-glycoprotein (P-gp) expressing
      cell line) were used as model to investigate the different accumulations of (E)-2
      (4-(diethylamino methyl) benzylidene)-5,6-dimethoxy-2,3-dihydroinden-one (BYZX)
      in the two kinds of cells. It was authenticated that whether BYZX was the
      substrate of P-gp. Meanwhile, the inhibitive effects of BYZX on the P-gp were
      investigated by determining the fluorescence intensity of rhodamine 123 in the
      model cells, with and without BYZX. A reversed-phase high-performance liquid
      chromatography (RP-HPLC) method was used to determine the accumulations of BYZX
      in the two cells. The results showed that the amount of BYZX accumulation in
      Bcap37/MDR1 cells were as many as those in Bcap37 cells (P > 0.05), and the
      concentrations of BYZX accumulated in the Bcap37/MDR1 cells did not increase when
      co-incubated with P-gp inhibitor verapamil. Furthermore, different concentrations
      of BYZX also had no effects on the efflux of rhodamine 123 (P > 0.05). These
      results indicated that there were no interactions between BYZX and P-gp. BYZX
      will not be pumped out of the cells, and it also not inhibited the P-gp. It was
      the useful advantage for its absorption.

PMID- 18338645
TI  - [Acid-sensitive polymer liposomes prepared by poly(2-ethylacrylic acid)
      alkylamide derivatives].
AB  - Poly (2-ethylacrylic acid) (PEAA) alkylamide derivatives were synthesized for
      constructing pH-sensitive liposomes by partially modification of carboxylic
      groups of PEAA with chemical reaction. These lipid derivatives of PEAA were
      synthesized by partially modification of carboxylic groups of PEAA with
      alkylamines. The acid-sensitive polymer associated liposomes were obtained by the
      method of polymer self-insertion in aqueous solutions through inserting
      hydrophobic lipid anchors of the polymer PEAA derivatives into the outer layer of
      vesicles. Factor effects on polymer insertion into liposomes were evaluated and
      the pH-sensitivity of the polymer associated liposomes was studied by calcein
      release assay. The PEAA-assoeiated-liposomes were prepared successfully by the
      methods of self-insertion. The PEAA-associated-liposomes are shown to be stable
      at neutral pH. (1) There was no correlate of anchor density of PEAA with length
      of the alkyl chain, but was positively correlated with the degree of PEAA
      modification. (2) Polymer insertion increased with initial ratio of polymer to
      lipid. (3) Unerting hydrophobic lipidr acidic conditions the associated polymer
      induces membrane disruption and fusion. (4) The PEAA-associated-liposomes shown
      pH-sensitive drug release property under acidic conditions. The anchored-poly
      (ethylacrylic acid) lipid derivatives can be useful in developing a potential pH
      sensitive drug delivery system.

PMID- 18338646
TI  - [Analysis of ITS sequences of some medicinal plants and their related species in
      Salvia].
AB  - Molecular systematic techniques were applied to reveal the genetic diversity of
      medicinal plants and their related species in Salvia. The internal transcribed
      spacer (ITS) as well as 5.8S rDNA sequences of 27 samples of Salvia were
      amplified using PCR method and sequenced. Mega 3.1 was used to analyze the
      genetic diversity within genus. The complete sequences of ITS plus 5.8S rDNA are
      about 612-617 bp. A phylogenetic tree generated by Neighbor-Joining method partly
      supported the morphological classification within Salvia, but incompatible
      results were also obtained in the treatment of phylogenetic positions of some
      species such as Salvia trijuga, Salvia flava var. flava and Salvia flava var.
      megalentha. The ITS regions of present Salria species showed considerable
      variation between subgenera in contrast with the conservative 5.8S rDNA
      sequences. The native Salvia species might have a different origin from the
      foreign species. The phylogenetic positions of subgenera and sections inferred by
      ITS analysis were comparable with that of traditional classification, while the
      phylogeny within sections is still doubtful due to limited information in ITS
      sequence and need to be further proved by other evidence. ITS analysis in this
      study supports the rationality of using species from Drymosphace section as
      substitute drug resources of Dan shen, but also reveals significant genetic
      differences between high mountain Dan shen species such as Salvia przewalskii
      with traditional Dan shen origins.

PMID- 18338647
TI  - [Increase of copy number of HMG-CoA reductase and FPP synthase genes improves the
      amorpha4,11-diene production in engineered yeast].
AB  - The gene encoding amorpha-4, 11-diene synthase was cloned from Artemisia annua L.
      Other two genes encoding the FPP synthase (FPPS) and HMG-CoA reductase (HMGR)
      were cloned from Saccharomyces cerevisiae. The cloned cDNAs were confirmed by DNA
      sequencing. Two expression vectors were constructed, one is named pGBT9/A/HMG/FPP
      harboring genes for HMG-CoA reductase and FPP synthase and the other is
      pYeDP60/G/AS, containing the gene encoding amorpha-4,11-diene synthase. Two kinds
      of engineered yeast were constructed: the first was named WHT [AS], which
      contained the plasmid pYeDP60/G/AS; the second was WHT [HMG + FPP + AS], in which
      the vectors pGBT9/A/ HMG/FPP and pYeDP60/G/AS were introduced by cotransformation
      mediated with LiOAc and PEG4000. The positive clones were identified for further
      fermentations. The samples from fermentations were analyzed by GC-MS for amorpha
      4,11-diene. The results show that engineered yeasts could produce amorpha-4,11
      diene. Moreover, the amorpha-4,11-diene production of WHT[ HMG + FPP + AS] and
      WHT[ AS] were 23.6 mg x L(-1) and 10 microg x L(-1), respectively. Its
      concentrations were reported as equivalents of valencene. The results showed the
      copy number increase of HMGR and FPPS genes can improve the production of amorpha
      4, 11-diene in the fermentation of engineered yeasts.

PMID- 18338648
TI  - [Percutaneous absorption of meloxicam patches in hairless mouse].
AB  - Meloxicam concentration in skin was determined following topical administration
      of meloxicam patches in hairless mouse. Samples were analysized by HPLC coupled
      with microdialysis sampling technique, in which in vivo recovery of probe was
      characterized by the retrodialysis method. It was indicated that the in vivo
      recovery of the probe was 14.0%. The range of steady state concentration of
      meloxicam in dialysate was 24-50 ng x mL(-1), and that was 170-360 ng x mL(-1) in
      the hairless mouse skin. Steady state concentration of meloxicam was reached
      shortly after the application of meloxicam patches, which was maintained during
      the period of experiment.

PMID- 18338649
TI  - [Optimizing the operating variables that affect the transfection experiment of
      antisense oligodeoxyribonucleotide by gas-filled microbubbles].
AB  - To optimize the operating variables that affect the transfection of antisense
      oligodeoxyribonucleotide (AS-ODNs) by insonated gas-filled lipid microbubbles,
      SF6-filled microbubbles were prepared by sonication-lyophilization method. An AS
      ODNs sequence and a breast cancer cell line SK-BR-3 were used to define the
      various operating variables determining the transfection efficiency of SF6-filled
      microbubbles. Three levels of mixing speed, different durations of mixing and
      various delay time before ultrasound were examined, separately. Transfection
      efficiency was detected by fluorescence microscopy. Transfection results with and
      without incubation of AS-ODNs and microbubbles before mixing cells were compared.
      From the results, there is no significant difference between the transinfection
      efficiency with or without incubation of AS-ODNs and microbubbles before mixing
      cells. AS-ODNs transfection efficiency showed an increasing trend with mixing
      speed and mixing duration, but there is a negative relationship with delay time
      before ultrasound. The optimum parameters for AS-ODNs transfection by SF6-filled
      microbubbles were found at a mixing speed of 40-50 r x min(-1) for 30-60 s with
      less than 60 s delay before ultrasound. For a successful transfection, long time
      of incubation with gene is essential for normal nonviral vectors such as
      liposomes or cationic lipid-polymer hybrids, because these vectors depend on
      endocytosis and membrane fusion to realize transfection. Unlike liposomes and
      cationic lipid-polymer hybrids, gas-filled lipid microbubbles depend on
      sonorporation effect to realize transfection. Therefore, the incubation of gene
      and microbubbles before mixing cells may not be necessary. Ultrasound-mediated AS
      ODNs transfection enhanced by gas-filled lipid microbubbles represents an
      effective avenue for gene transfer.

PMID- 18338650
TI  - [Synthesis and antitumor activity of benzoic nitrogen mustard derivatives].
AB  - To study the effect of isoprenoid and aliphatic saturated alcohols as modificator
      on benzoic nitrogen mustard, the intermediate 4-[N,N-bis(2-chloroethyl) amino]
      benzoic acid 4 was prepared in four steps utilizing p-amino benzoic acid as the
      starting material. Target compounds were synthesized by the catalytic
      esterification of DCC/DMAP and the structures of the six new esters were
      characterized by elemental analysis, 1H NMR, 13C NMR and MS. Antitumor activities
      were evaluated in vitro using MTT assay. The result showed that some derivatives
      were more potent than the intermediate 4, and compound 5c modified with dodecanol
      exhibited similar activity to the commercial drug melphalan.

PMID- 18338651
TI  - Overview of acne and its treatment.
AB  - Acne affects more than 85% of teenagers in the United States and often continues
      into adulthood. The most deleterious form can result in permanent scarring on the
      face, chest, and back. Although the pathogenic features of acne are well known,
      the initiating factor remains unknown. Isotretinoin is effective against all of
      the pathogenic features of acne but is contraindicated in pregnant women and has
      been associated with elevations in triglyceride levels. Combination regimens
      appear to be effective, but physicians should avoid prescribing complicated
      treatment regimens. Hormone therapy has been found to improve acne in some women
      and should be considered in appropriate candidates. Although the list of
      available and effective agents appears to be extensive, several are
      contraindicated in pregnant women, and long-term use of antibiotics to target
      inflammation has been linked to agranulocytosis and Stevens-Johnson syndrome.
      Further investigation into agents that can reduce sebum production is warranted.

PMID- 18338652
TI  - Pharmacology of hormonal contraceptives and acne.
AB  - Higher free testosterone levels in women are a function of lower levels of sex
      hormone-binding globulins (SHBG), higher levels of total testosterone, or both.
      When free testosterone levels are decreased, sebum production, a pathogenic
      feature of acne vulgaris, is also decreased. Oral contraceptives (OCs) decrease
      free testosterone levels by reducing testosterone production by the ovaries and
      adrenal glands, increasing SHBG, and inhibiting conversion of free testosterone
      to dihydrotestosterone. Studies have shown that the progestin component of OCs
      lowers androgen levels, which are directly associated with the development of
      acne lesions. Currently, 3 OCs have received approval for acne from the US Food
      and Drug Administration. For patients with acne who are already benefiting from
      OC treatment, there is no need to change the OC; however, when an OC proves
      insufficient against sebum production, switching to a formulation that is
      approved for acne is recommended.

PMID- 18338653
TI  - Hormonal contraceptives for acne management.
AB  - Acne vulgaris affects 42 million people, more than half of whom are women older
      than 25 years. Treatment for acne includes oral and topical antibiotics,
      retinoids, and hormonal therapy in the form of oral contraceptives (OCs). OCs
      reduce acne lesions by increasing estrogen levels and sex hormone-binding
      globulins, and by decreasing free testosterone and androgen levels. Several
      studies have shown that drospirenone, a progestin available in certain OCs,
      minimizes the potential negative effect the progestin has on acne. Women with
      moderate acne vulgaris who seek contraception and teenagers with acne who refuse
      antibiotics or in whom topical antibiotics are ineffective might be candidates
      for drospirenone-containing OCs.

PMID- 18338654
TI  - Oral contraceptives: mechanism of action, dosing, safety, and efficacy.
AB  - The most widely used form of hormonal contraception is the combination oral
      contraceptive (OC). Combination OCs can be monophasic, providing the same dose of
      estrogen and progestin daily, or multiphasic, offering varying doses of hormones
      throughout a 21- or 28-day cycle. The objective of OCs is to suppress ovulation
      by manipulating events throughout the ovulatory cycle to prevent pregnancy. The
      progestin and estrogen components of OCs suppress the mid-cycle surge of
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The overall
      effect is to decidualize the endometrial bed and suppress mitotic activity.
      Initial formulations of OCs in the 1960s attempted to mimic the natural cycle;
      however, providing high doses of estrogen rather than lower doses of combined
      estrogen and progestin resulted in greater risk of serious adverse events. Today,
      OCs provide far lower levels of estrogen and progestin. The availability of
      formulations with drospirenone, a unique progestin pharmacokinetically similar to
      progestin and similar in structure to spironolactone, should widen usage of OCs.
      Although OCs are still associated with increased risk in certain patients and are
      contraindicated in others, they remain effective but require diligent usage.

PMID- 18338655
TI  - Tailoring individualized treatment plans for acne.
AB  - Because acne is a complex multifactorial disorder, combination treatment may be
      required to target its various pathogenic factors. Combination treatments also
      offer the most improvement over the shortest time. Oral contraceptives (OCs) are
      an excellent treatment, and clinicians should consider them a first-line option
      as part of combination therapy in women with acne.

PMID- 18338656
TI  - Malpractice consult. Your risks when practicing telemedicine.

PMID- 18338657
TI  - Employed? What your boss wants from you.

PMID- 18338658
TI  - Health plans: all or nothing could be here to stay.

PMID- 18338659
TI  - Job sharing: flexibility has a price.

PMID- 18338660
TI  - A machine that may help your patients.

PMID- 18338661
TI  - Smarter scheduling puts you in control.

PMID- 18338662
TI  - NT-proBNP values and Weber functional class in patients with chronic heart
      failure.
AB  - OBJECTIVE: To assess the correlation between NT-proBNP values and Weber
      functional class as determined by cardiopulmonary exercise testing (CPET) in
      patients with chronic heart failure (CHF). METHODS: We studied 95 patients, 68
      male, mean age 50.4 +/- 10.5 years, with CHF due to dilated cardiomyopathy (DCM),
      65% of non-ischemic etiology, classified by symptom-limited treadmill CPET
      (modified Bruce protocol) as follows: 48 Weber class A, 27 class B, 16 class C
      and 4 class D. NT-proBNP values (pg/ml) were determined after 15 minutes rest
      immediately prior to CPET. There were no significant differences between the
      groups in gender, age or percentage of patients taking ACE inhibitors or ARBs and
      beta-blockers. Left ventricular ejection fraction was higher in class A and B
      (27.6+/-8.3%) than in class C and D (19.7+/-6.2%, p=0.001). Serum creatinine was
      lower in class A (0.97+/-0.22 mg/dl) than in classes C or D (1.16+/-0.26,
      p=0.006). RESULTS: NT-proBNP was: class A=1325.8+/-1500.3, class B=3473.0+/
      2575.3 (p<0.001 vs. class A), class C=6193.1+/-2066.8 (p<0.001 vs. A and B),
      while in class D it was 11821.8+/-5489.7. There was an overall significant
      correlation between NT-proBNP and peak oxygen uptake (r=-0.66, p<0.001). On ROC
      curve analysis, an NT-proBNP value of 1766.5 pg/ml was found to be the best cut
      off to discriminate class A vs. non-A (AUC=0.896, p<0.001, 95% CI 0.834 to 0.957,
      sensitivity=79%, specificity=83%), while a value of 5029.0 was the best
      discriminator of class B vs. class C or D (AUC=0.865, p<0.001, 95% CI 0.760 to
      0.970, sensitivity=82%, specificity=80%). CONCLUSIONS: In patients with CHF due
      to DCM, NT-proBNP values correlate with Weber class as determined by CPET, and
      this study presents discriminative values.

PMID- 18338663
TI  - Correlation between NT-proBNP values and changes in functional capacity in
      patients with chronic heart failure.
AB  - OBJECTIVE: We set out to evaluate whether changes in N-terminal pro-brain
      natriuretic peptide (proBNP) can predict changes in functional capacity, as
      determined by cardiopulmonary exercise testing (CPET), in patients with chronic
      heart failure (CHF) due to dilated cardiomyopathy (DCM). METHODS: We studied 37
      patients with CHF due to DCM, 81% non-ischemic, 28 male, who performed symptom
      limited treadmill CPET, with the modified Bruce protocol, in two consecutive
      evaluations, with determination of proBNP after 10 minutes rest prior to CPET.
      The time between evaluations was 9.6+/-5.5 months, and age at first evaluation
      was 41.1+/-13.9 years (21 to 67). RESULTS IN THE FIRST AND SECOND EVALUATIONS
      RESPECTIVELY WERE: NYHA functional class >II 51% and 16% (p<0.001), sinus rhythm
      89% and 86.5% (NS), left ventricular ejection fraction 24.9+/-8.9% and 26.6+/
      8.6% (NS), creatinine 1.03+/-0.25 and 1.09+/-0.42 mg/dl (NS), taking ACE
      inhibitors or ARBs 94.5% and 100% (NS), beta-blockers 73% and 97.3% (p<0.001),
      and spironolactone 89% and 89% (NS). We analyzed the absolute and percentage
      variation (AV and PV) in peak oxygen uptake (pVO2--ml/kg/min) and proBNP (pg/ml)
      between the two evaluations. RESULTS: (1) pVO2 AV: -17.4 to 15.2 (1.9+/-5.7);
      pVO2 PV: -56.1 to 84% (11.0+/-25.2); proBNP AV: -12850 to 5983 (-778.4+/-3332.5);
      proBNP PV: -99.0 to 379.5% (-8.8+/-86.3); (2) The correlations obtained--r value
      and p value [r (p)]--are shown in the table below; (3) We considered that a
      coefficient of variation of pVO2 PV of >10% represented a significant change in
      functional capacity. On ROC curve analysis, a proBNP PV value of 28% showed 80%
      sensitivity and 79% specificity for pVO2 PV of >10% (AUC=0.876, p=0.01, 95% CI
      0.75 to 0.99). CONCLUSIONS: In patients with CHF due to DCM, changes in proBNP
      values correlate with variations in pVO2, as assessed by CPET. However, our
      results suggest that only a proBNP PV of >28% predicts a significant change in
      functional capacity.

PMID- 18338664
TI  - B-type natriuretic peptide in heart failure: let's trust it ... but not too much.

PMID- 18338665
TI  - Variations in inflammatory markers in acute myocardial infarction: a longitudinal
      study.
AB  - Inflammation is now considered a key component of atherosclerosis, from fatty
      streak formation to plaque rupture, subsequent thrombosis, and progressive
      mechanical and dynamic obstruction. Rupture of the arterial plaque's fibrous cap
      exposes tissue factors present in the necrotic core, triggering inflammatory
      signaling, cell adhesion, and the coagulation cascade that eventually leads to
      thrombus. Cytokines and adhesion molecules are key components of these events
      that contribute to the development of an atherosclerotic plaque. The cytokine TNF
      alpha and intercellular adhesion molecule-1 (ICAM-1) are indicators of basal
      inflammation, while the soluble forms of adhesion molecules such as CD40L and P
      selectin indicate the extent of platelet activation. This study reports on the
      follow-up of 17 patients with confirmed acute myocardial infarction (AMI group)
      undergoing angioplasty and a matched control group of 16 patients without
      coronary artery disease as verified by coronary angiography. Patients from the
      AMI group were assessed at the onset of the acute coronary syndrome, within 24 h,
      before the administration of glycoprotein IIb/IIIa inhibitors and coronary
      angioplasty, and during the recovery period, two and 40 days after intervention.
      For both groups, clinical characteristics were documented and serum
      concentrations of soluble CD40L, P-selectin, ICAM-1, TNF-alpha, and conventional
      biochemical indicators were analyzed. For AMI patients, these indicators were
      recorded at study entry and during follow-up. Concentrations of cytokines and
      adhesion molecules were measured using commercial immunoassay (ELISA) kits.
      Significant variations in sP-selectin were observed relative to the control
      group. Immediately after myocardial infarction, sP-selectin levels rose markedly,
      followed by a sharp decrease two days later. After 40 days of recovery, sP
      selectin levels rose again, returning to the initial values. Variations in sCD40L
      levels were not significant relative to controls. However, sCD40L concentrations
      tended to fall until the second day after infarction, followed by a rise, and by
      the 40th day of recovery levels were slightly higher than controls. Unlike sCD40L
      and sP-selectin, consistently higher levels of TNF-alpha relative to controls
      were observed, which were only significant after 40 days of recovery. No
      significant variations were observed for ICAM-1 serum concentrations in the AMI
      group. The variations observed demonstrate the role of inflammatory markers in
      AMI progression and highlight the importance of systemic inflammation in disease
      evolution. The increased concentration of sP-selectin at infarction onset is
      evidence of thrombosis and platelet activation. Later, during the recovery period
      when hemodynamic variables are returning to stability in part due to medication,
      rises in circulating levels of sCD40L and cytokines such as TNF-alpha may reflect
      the role of these molecules in the recovery of endothelial and myocardial
      tissues.

PMID- 18338666
TI  - Admission glycemia: a predictor of death after acute coronary syndrome in non
      diabetic patients?
AB  - BACKGROUND: Previous studies have demonstrated that acute phase hyperglycemia is
      associated with increased in-hospital mortality in diabetic patients admitted
      with acute coronary syndrome (ACS), but this has not been clearly demonstrated in
      non-diabetic patients. The present study was designed to determine whether
      admission hyperglycemia (AG) is an independent predictor of in-hospital and six
      month mortality after ACS in non-diabetic patients. METHODS: This was a
      retrospective cohort study of 426 non-diabetic patients consecutively admitted
      with ACS. The patients were stratified into quartile groups according to AG,
      which was also analyzed as a continuous variable. Vital status was obtained at
      six-month follow-up in 96.8% of the patients surviving hospitalization. Logistic
      regression analysis was used to identify independent predictors of in-hospital
      and six-month death. RESULTS: Of the 426 patients included in the study (age 62.6
      years+/-13.1, 77% male), 22 (5.4%) patients died during hospitalization and 20
      (5.2% of the patients surviving hospitalization) within six months of ACS. Mean
      AG was 134.89 mg/dl+/-51.95. The higher the AG, the more probable was
      presentation with ST-segment elevation ACS (STEMI), anterior STEMI, higher heart
      rate, Killip class higher than one (KK >1), higher serum creatinine and greater
      risk of in-hospital and six-month death. In multivariate analysis, only age
      (OR=1.10; 95% CI 1.04-1.17), STEMI (OR=3.02; 95% CI 1.07-8.50), AG (OR=1.073; 95%
      CI 1.004-1.146), serum creatinine (OR=1.10; 95% CI 1.009-1.204) and KK >1 on
      admission (OR=4.65; 95% CI 1.59-13.52) were independently associated with in
      hospital death. Age (OR=1.07; 95% CI 1.03-1.12), serum creatinine (OR=1.09; 95%
      CI 1.01-1.18) and in-hospital development of heart failure (OR=2.34; 95% CI 1.07
      5.10) were independently associated with higher risk of death within six months
      of ACS. CONCLUSIONS: AG is an independent predictive factor of in-hospital death
      after ACS in non-diabetic patients. Although it did not show an independent
      association with higher risk of six-month death, AG appears to contribute to it,
      since the risk is greater the higher the AG. Its predictive value may have been
      blunted by the insufficient power of the sample and/or by the time interval
      between acquisition of AG and the evaluated endpoint.

PMID- 18338667
TI  - Left ventricular noncompaction: case report and literature review.
AB  - Isolated left ventricular noncompaction (ILVNC) is a rare cause of dilated
      cardiomyopathy. It is morphologically characterized by a spongy left ventricle
      with prominent myocardial trabeculations. Although not proven, it is nowadays
      widely accepted that ILVNC results from arrest of the normal myocardial
      compaction process during early embryonic life. ILVNC can occur in a familial
      form and certain genes coding proteins linking the extracellular matrix and the
      cytoskeleton have been related to this disorder. Clinically, the disease courses
      with heart failure, embolic and arrhythmic events being a common cause of
      morbidity and mortality. Current diagnostic criteria for ILVNC are based on
      clinical and echocardiographic data. Therapy is based on current heart failure
      guidelines, with particular emphasis on anticoagulation and prevention of fatal
      arrhythmias. The authors describe the case of a 29-year-old man admitted to the
      Cardiology Department with decompensated heart failure (NYHA IV), a dilated left
      ventricle with severe systolic dysfunction, an apical thrombus and highly
      trabeculated walls. Clinical evolution was favorable after standard pharmacologic
      therapy for heart failure and levosimendan, the patient being discharged in NYHA
      class I-II. Eighteen months later, despite partial recovery of left ventricular
      systolic function, the patient suffered sudden death. A review and discussion of
      the literature presented regarding etiopathogenesis, diagnostic criteria and
      therapeutic options.

PMID- 18338668
TI  - Cardiovascular toxicity of cocaine of iatrogenic origin. Case report.
AB  - The use of cocaine as an illicit drug is associated with various cardiovascular
      events. In recent decades, because of growing levels of consumption, there has
      been an increasing incidence of these complications. At the same time, cocaine is
      also widely used as a local anesthetic, mainly in nasal surgery. Its application
      in this context is controversial due to the potential associated adverse effects.
      The authors report the case of a 29-year-old patient, with no known
      cardiovascular risk factors, admitted for elective nasal surgery, under general
      anesthesia combined with topical application of cocaine. During surgery the
      patient developed hemodynamic instability in the context of ventricular
      arrhythmias, after which she presented evolving electrocardiographic changes and
      increased levels of myocardial necrosis markers, diagnostic of non-ST-segment
      elevation acute coronary syndrome. The authors review the cardiovascular
      complications associated with cocaine use and the underlying pathophysiologic
      mechanisms and discuss the role of cocaine as a topical anesthetic.

PMID- 18338669
TI  - Metabolic syndrome: an evolving concept.
AB  - Metabolic syndrome is a cluster of interrelated cardiometabolic risk factors that
      are associated with an increased risk for both type 2 diabetes and
      atherosclerotic cardiovascular disease. These risk factors include visceral
      obesity, atherogenic dyslipidemia (elevated triglycerides and low HDL
      cholesterol), elevated blood pressure, dysglycemia (pre-diabetes or diabetes) and
      a prothrombotic and proinflammatory state. The condition is progressive,
      beginning with borderline risk factors, and worsens over time. Primary treatment
      is lifestyle therapy--weight loss, increased physical activity and
      antiatherogenic diet. But, as the metabolic syndrome progresses, drug therapy
      directed at individual risk factors may be needed.

PMID- 18338670
TI  - A rare case of a pericardial congenital defect.

PMID- 18338671
TI  - Half a century.

PMID- 18338672
TI  - On the primacy of molecular processes in determining response rates under
      variable-ratio and variable-interval schedules.
AB  - This study focused on variables that may account for response-rate differences
      under variable-ratio (VR) and variable-interval (VI) schedules of reinforcement.
      Four rats were exposed to VR, VI, tandem VI differential-reinforcement-of-high
      rate, regulated-probability-interval, and negative-feedback schedules of
      reinforcement that provided the same rate of reinforcement. Response rates were
      higher under the VR schedule than the VI schedule, and the rates on all other
      schedules approximated those under the VR schedule. The median reinforced
      interresponse time (IRT) under the VI schedule was longer than for the other
      schedules. Thus, differences in reinforced IRTs correlated with differences in
      response rate, an outcome suggestive of the molecular control of response rate.
      This conclusion was complemented by the additional finding that the differences
      in molar reinforcement-feedback functions had little discernible impact on
      responding.

PMID- 18338673
TI  - The emergence of conditioned reinforcement from observation.
AB  - We report an experiment in which observations of peers by six 3-5-year-old
      participants under specific conditions functioned to convert a small plastic disc
      or, for one participant, a small piece of string, from a nonreinforcer to a
      reinforcer. Prior to the observational procedure, we compared each participant's
      responding on (a) previously acquired performance tasks in which the child
      received either a preferred food item or the disc (string) for correct responses,
      and (b) the acquisition of new repertoires in which the disc (string) was the
      consequence for correct responses. Verbal corrections followed incorrect
      responses in the latter tasks. The results showed that discs and strings did not
      reinforce correct responses in the performance tasks, but the food items did; nor
      did the discs and strings reinforce correct responses in learning new
      repertoires. We then introduced the peer observation condition in which
      participants engaged in a different performance task in the presence of a peer
      who also performed the task. A partition blocked the participants from seeing the
      peers' performance. However, participants could observe peers receiving discs or
      strings. Participants did not receive discs or strings regardless of their
      performance. Peer observation continued until the participants either requested
      discs or strings repeatedly, or attempted to take discs or strings from the
      peers. Following the peer observation condition, the same performance and
      acquisition tasks in which participants had engaged prior to observation were
      repeated. The results showed that the discs and strings now reinforced correct
      responding for both performance and acquisition for all participants. We discuss
      the results with reference to research involving nonhuman subjects that
      demonstrated the observational conditioning of reinforcers.

PMID- 18338674
TI  - Induced attack during fixed-ratio and matched-time schedules of food
      presentation.
AB  - Adjunctive or induced behavior is generated during a variety of schedules of
      reinforcement. Several theoretical conceptualizations suggest that rate of
      reinforcement is the primary variable controlling the strength or levels of
      induced behavior. The operant response requirement within the schedule context
      has not been extensively studied as a determinant of induced responding. In the
      present study, levels of induced attack by food-deprived pigeons against
      restrained conspecifics were compared during response-dependent and response
      independent schedules of food presentation equated or yoked interval-by-interval
      for reinforcement frequency. Experiment 1 compared levels of attack induced by
      fixed-ratio schedules of key pecking and yoked "matched-time" schedules.
      Experiment 2 similarly compared chained fixed-ratio 1 fixed-ratio 74 and yoked
      chained matched-time matched-time schedules. In both experiments, the response
      dependent schedules generated greater levels (amount and probability) of induced
      attack than the response-independent time-based schedules. Thus, the ratio
      response requirement may be an important determinant of levels of induced
      responding, and the lower levels of attack observed during the response
      independent condition may not be due to the absence of stimuli predicting food
      presentations. It is concluded that rate of reinforcement is not the sole
      variable determining levels of induced responding and that response-based and
      time-based schedules differ in their generation of induced responding.

PMID- 18338675
TI  - Rapid acquisition of preference in concurrent chains when alternatives differ on
      multiple dimensions of reinforcement.
AB  - Pigeons responded in a concurrent-chains procedure in which terminal-link
      reinforcer variables were changed unpredictably across sessions. In Experiment 1,
      the terminal-link schedules were fixed-interval (FI) 8 s and FI 16 s, and the
      reinforcer magnitudes were 2 s and 4 s. In Experiment 2 the probability of
      reinforcement (100% or 50%) was varied with immediacy and magnitude. Multiple
      regression analyses showed that pigeons' initial-link response allocation was
      determined by current-session reinforcer variables, similar to previous studies
      which have varied only immediacy (Grace, Bragason, & McLean, 2003). Sensitivity
      coefficients were positive and statistically significant for all reinforcer
      variables in both experiments. Analyses of responding within individual sessions
      showed that final levels of preference for dominated sessions, in which all
      reinforcer variables favored the same terminal link, were more extreme than for
      tradeoff sessions in which at least one reinforcer variable favored each
      alternative. This result implies that response allocation was determined by
      multiple reinforcer variables within individual sessions, consistent with the
      concatenated matching law. However, in Experiment 2, there was a nonlinear
      (sigmoidal) relationship between response allocation and relative value, which
      suggests the possibility that reinforcer variables may interact during
      acquisition, contrary to the matching law.

PMID- 18338676
TI  - Rapid acquisition of preference in concurrent chains: effects of d-amphetamine on
      sensitivity to reinforcement delay.
AB  - The purpose of this study was to examine effects of d-amphetamine on choice
      controlled by reinforcement delay. Eight pigeons responded under a concurrent
      chains procedure in which one terminal-link schedule was always fixed-interval 8
      s, and the other terminal-link schedule changed from session to session between
      fixed-interval 4 s and fixed-interval 16 s according to a 31-step pseudorandom
      binary sequence. After sufficient exposure to these contingencies (at least once
      through the pseudorandom binary sequence), the pigeons acquired a preference for
      the shorter reinforcement delay within each session. Estimates of the sensitivity
      to reinforcement immediacy were similar to those obtained in previous studies.
      For all pigeons, at least one dose of d-amphetamine attenuated preference and,
      hence, decreased estimates of sensitivity to reinforcement immediacy; in most
      cases, this effect occurred without a change in overall response rates. In many
      cases, the reduced sensitivity to reinforcement delay produced by d-amphetamine
      resulted primarily from a decrease in the asymptotic level of preference achieved
      within the session; in some cases, d-amphetamine produced complete indifference.
      These findings suggest that a reduction in the sensitivity to reinforcement delay
      may be an important behavioral mechanism of the effects of psychomotor
      stimulants.

PMID- 18338677
TI  - The Journal of the Experimental Analysis of Behavior at fifty.
AB  - The Journal of the Experimental Analysis of Behavior was founded in 1958 by a
      group of male psychologists, mainly from the northeastern USA and connected with
      either Harvard or Columbia. Fifty years later about 20% of both editors and
      authors reside outside this country and almost the same proportion is made up of
      women. Other changes in the journal include having its own website for more than
      a decade and now publishing online as well as on paper. A recent connection with
      PubMed Central of the National Library of Medicine has made possible the
      completely free electronic presentation of the entire archive of about 3,800
      articles.

PMID- 18338679
TI  - Control, prediction, order, and the joys of research.
AB  - JEAB's first decade featured control of individual behavior by operant
      contingencies, where the experimenter could interact with a subject in real time
      and obtain fairly immediate evidence of control, with the possibility of direct
      extension to applied settings. In subsequent decades, emphasis shifted toward
      long-term parametric studies with quantitative analyses of individual and group
      data. As a result, the reinforcers for the experimenter shifted from controlling
      behavior to uncovering and describing order, often using mathematical
      expressions. The same sorts of reinforcers are available for quantitative
      descriptions of aggregate behavioral data that may inform public policy.

PMID- 18338678
TI  - The Journal of the Experimental Analysis of Behavior at zero, fifty, and one
      hundred.
AB  - The experimental content areas represented in JEAB in its first volume (1958) and
      50 years later in Volume 87 are in many ways similar with regard to research on
      schedules of reinforcement, research with human subjects, and several other
      topics. Experimental analysis has not been displaced by quantitative analysis.
      Much less research on aversive control has been published in recent than in
      earlier years. Wishes for progress in the next 50 years include experiments on
      verbal behavior, the sources of novel behavior, and observing responses based on
      stimuli correlated with escape or avoidance.

PMID- 18338680
TI  - Behavior analysis: thriving, but how about its future?
AB  - Behavior analysis has been thriving by continuing to make important theoretical
      and empirical contributions to a wide array of problems, as well as by
      contributing to interdisciplinary research. Applied research in behavior analysis
      is flourishing. Despite these positive signs there may be an erosion of support
      for basic research in animal learning and behavior, including behavior analysis.
      Increased attention by behavior analysts to fundamental problems in areas of
      cognition, including decision-making and language, may help behavior analysis to
      evolve more successfully. An experimental analysis of gambling may prove
      particularly fruitful.

PMID- 18338681
TI  - Jeab at 50: coevolution of research and technology.
AB  - Evidence of how behavioral research and technology have evolved together abounds
      in the history of the Journal of the Experimental Analysis of Behavior (JEAB).
      Technology from outside the discipline (exogenous), from such disciplines as
      electronics and computer science, has been adapted for use in behavioral
      research. Technology from within the discipline (endogenous) has developed from
      both basic behavioral research and existing apparatus. All of these sources of
      technology have contributed to the corpus of behavioral research as it has
      evolved in JEAB. Such research, in turn, has provided the environmental pressure
      necessary for continuing technological evolution both within and outside the
      discipline. The new technology thus evolved further spurs research along in novel
      directions. This dynamic coevolutionary interplay between research and technology
      is an important variable in the past, present, and future of JEAB.

PMID- 18338682
TI  - Jeab and the Skinnerian interpretation of behavior.
AB  - At one time, JEAB editorial policy was perceived by some to consist mainly of
      dogmatically enforcing a Skinnerian interpretation of all findings reported in
      the journal. Partly in response to that undeserved reputation, the journal
      explicitly defined itself as the place to publish research on the behavior of
      individual organisms, and not as a place that encourages any particular
      theoretical orientation. My own view is that this should not be the journal's
      identity; instead, JEAB should be the one journal that seriously considers
      Skinnerian (and related environment based) interpretations of empirical results,
      whether or not the study involved an analysis of individual subject behavior and
      whether or not the Skinnerian analysis is ultimately endorsed by the author.

PMID- 18338683
TI  - A rare case of trypanosomiasis in a two month old infant in Mumbai, India.
AB  - Human Trypanosomiasis is a rare occurrence in India. In the cases reported so far
      the disease causative species have been the species infective to animals viz.,
      Trypanosoma lewisi and Trypanosoma evansi. These animal species usually non
      pathogenic in humans can acquire the desired virulence and emerge as human
      pathogens causing serious disease, in the right combination of environmental,
      host related and organism related factors. We report here a case of
      trypanosomiasis caused by the rodent parasite T. lewisi in a two months old
      infant in urban Mumbai. Under the fastly changing environmental scenario there is
      an urgent need to be prepared for the emerging zoonoses. Any unusual disease
      occurrence in a given geographical area acquires a special significance in this
      context and should be reported to assess its public health importance and be
      prepared to deal with the consequent challenges posed, if any.

PMID- 18338684
TI  - Evaluation of Og4C3 antigen ELISA as a tool for detection of bancroftian
      filariasis under lymphatic filariasis elimination programme.
AB  - Diagnosis of Lymphatic Filariasis by microscopic examination of thick blood films
      (TBF) collected between 8.30 pm to 12 midnight, though highly specific is
      operationally problematic. We evaluated the TropBio Og4C3 serum ELISA as a tool
      for detection of W. bancrofti microfilaria carriers using Dried Blood Spots
      (DBS). The study was carried out in two parts (i) to test the sensitivity and
      specificity of the ELISA test for detection of circulating filarial antigen (CFA)
      in microfilaria (Mf) carriers vis-a-vis the conventional thick blood film (TBF)
      microscopy and its persistence in different categories of individuals during the
      course of disease viz., Endemic normals (n=51), microfilaria (Mf) carriers
      (n=27), acute cases (n=27), chronic cases (n=50) and a control group of non
      endemic normals (n=48) using sera samples and ii) to study the utility of finger
      prick Dried Blood Spots (DBS) collected on filter paper for detection of Mf
      carriers and its comparison with another antigen detection assay, the
      Immunochromatographic test (ICT). Considering the non-endemic normals and
      microfilaria carriers, the ELISA test was found to have 100% sensitivity and
      94.12% specificity for detection of Mf carriers in sera samples. The CFA was
      absent in majority of the subjects tested under other categories with a
      positivity of 7.8% among endemic normals, 11.12% among acute cases, 7.84% among
      chronic cases and 6.25% among nonendemic normals. Comparison of finger prick DBS
      and sera samples by ELISA vis-a-vis the ICT, carried out on Mf carriers (n=91)
      and endemic normals (n=97), showed a positivity of 88 (96.7%) in DBS as against
      86 (94.5%) in sera samples and 88 (96.7%) by ICT, amongst Mf carriers, with a
      statistically significant correlation in antigen units between sera and DBS
      samples (r = 0.959, p = 0.000) amongst the microfilaria carriers. Out of 97
      endemic normals, 19 (19.6%) sera and 17 (17.5%) DBS samples tested positive by
      ELISA while as 12(12.4%) tested positive by ICT, again with a statistically
      significant correlation between the antigen units in sera and DBS samples (r =
      0.942, p = 0.000). DBS prepared from 25 microl of blood were found to be as
      sensitive as 50 microl for antigen detection. Antigen positivity detected from
      DBS collected during day and night from known microfilaria carriers (n=27) showed
      a statistically insignificant difference (p = 0.125) and a significant
      correlation in antigen units (r = 0.820 and p = 0.013). In view of the comparable
      results of ELISA, ICT and TBF microscopy, it is concluded that the TropBio Og4C3
      ELISA using finger prick DBS can be used as an alternate to TBF microscopy for
      detection of bancroftian Filariasis under the LFE programme.

PMID- 18338685
TI  - Schistosoma haematobium and urinary tract pathogens co-infections in a rural
      community of Edo State, Nigeria.
AB  - A survey of S. haematobium and other urinary tract pathogens co-infection was
      carried out among 198 volunteers in Ihieve, Ogben, a rural community in Owan East
      Local Government Area of Edo State, Nigeria. Of these, 118 (59.5%) had S.
      haematobium ova in their urine samples. Light infection (< or =50 ova/l0 ml)
      occurred among 49 (24.7%) volunteers and 59 (29.8%) inhabitants had heavy
      infections (> 50 ova/10 ml). The children 68 (64.2%) were more infected their the
      adults 50 (54.3%). This difference was statistically significant at (chi2 =
      60.37, P < 0.05). The prevalence of S. haematobium among the males 80 (71.4%) was
      higher than their female counterparts 38 (41.9%) and this difference is
      statistically significant at (t = 1.28) Bacteriuria and bacterial isolates
      occurred among 60 (30.3%) with S haematobium infection. Three nitrate reducing
      bacterial isolates namely; Klebsiella sp and Staphylococcus aureus, Escherichia
      coli and a fungus; Candida albicans were reported in their urine cultures.
      Multiple infections were observed among 43 S. haematobium infected persons. The
      antibiogram of the isolates indicated that Nitrofurantoin, Gentamycin and otramax
      were the most effective drugs for the management of bacterial infections among
      these volunteers. All the bacterial isolates were resistant to Cloxacillin and
      Augmentum. The C. albicans were sensitive to Diflucan, Nizoral, Gynotravogen,
      Gynotrosydovule, Gyno-daktarin and Mycostatin.

PMID- 18338686
TI  - Anti-malarial activity of Eclipta alba against Plasmodium berghei infection in
      mice.
AB  - The anti-malarial activity of Eclipta alba leaves extract was evaluated against
      Plasmodium'berghei ANKA strain in mice. A standard inoculum of 1 x 10(6) infected
      erythrocytes was used. The methanolic leaf extract (250-750 mg/kg) produced a
      dose-dependant chemosupression or schizontocidal effect during early and
      established infection and high mean survival time (m.s.t.) values particularly in
      the group administered 750 mg/kg/day of extract. The plant extract also exhibited
      repository activity. The results of the preliminary studies carried out with E.
      alba are encouraging, which can be exploited in malaria therapy.

PMID- 18338687
TI  - Perception of risk and potential occupational exposure to HIV/AIDS among medical
      interns in Delhi.
AB  - A cross sectional study was conducted among 129 medical interns of Maulana Azad
      Medical College, New Delhi for assessing the perceived levels of risk of
      acquiring HIV infection in the health care settings among medical interns,
      reasons for the same and their exposure to situations having potential of HIV
      transmission. Majority of the interns (68.3%) perceived themselves to be at a
      very high/high risk of acquiring HIV infection during their medical career. The
      common reasons for perceived risk of acquiring HIV infection were getting
      injuries due to needle pricks/cuts during surgical procedures (32.4%), frequent
      exposure to the blood/ secretions of patients (28.5%) and insufficient
      availability of gloves (17.6%). Some (23.2%) were of the opinion that students in
      future might lose interest in the medical profession due to increasing risk of
      HIV infection and few (3.1%) were even considering to leave the medical
      profession for the same reason. Majority of the interns (72.9%) had experienced
      needle pricks and more than half (53.7%) of them even had had blood splashes in
      their eyes/ nose/ mouth during surgical procedures. The findings of the study
      call for efforts for bringing a reduction in the risk perception of the interns
      through awareness campaigns and reorientation trainings, ensuring availability of
      gloves and other items necessary for observing universal work precautions and
      proper disposal of potentially contaminated articles.

PMID- 18338688
TI  - A comparison of HIV/AIDS awareness between self-help group leaders and other
      women in the villages of Primary Health Centre, Anji.
AB  - A Cross-sectional study was undertaken to compare the level of awareness about
      HIV/AIDS between women's self-help group leaders and other women in the villages
      of primary health centre area, Anji. 82 leaders of women's self-help groups i.e.
      president and secretary of each 41 women's self-help groups promoted by Kasturba
      Rural Health Training Centre, Anji in area Primary Health Centre, Anji and 98
      women other than leaders of self-help group from the same villages were selected
      for the study. Both the groups were in reproductive age groups. The leaders of
      Self-help groups had better level of education and awareness about HIV/AIDS than
      other women in the village. Considering the significant high level of awareness
      regarding HIV/AIDS, the leaders of women's self-help groups could act as
      potential resource persons for the delivery of health education about prevention
      of HIV/AIDS to other women in the villages of Primary Health Centre, Anji.

PMID- 18338689
TI  - Leptospirosis: clinical presentation and correlation with serovars.
AB  - A total of 2400 patients with pyrexia of unknown origin and or suspected
      leptospirosis were included in this study. Dark field microscopy detected
      Leptospira in 690 cases, Leptospira serological Investigations proved positive in
      570 out of these 690 patients. Among them 212 had the classical icteric and the
      other 358 had anicteric type of presentation. Notably eptospira interrogans
      serovar ictero haemorrhagiae infection was encountered in 212 patients. In 30
      patients, who had multi organ dysfunction which included renal failure, hepatic
      dysfunction or meningitis was due to Leptospira interrogans Serovar cannicola.
      Coexsistense of leptospirosis and hepatitis B virus infection were noted in 15
      patients. Antibody to Leptospira interrogans was demonstrated by Micro
      agglutination test (MAT) in addition to dark field microscopy positivity in these
      cases. Similarly HIV antibody was demonstrated in 30 of the 330 anicteric
      patients. 554 out of 570 cases responded to intra venous penicillin (216), and
      oral Doxycycline (182) and Augmentin (156), and the remaining 16 patients
      succumbed to death.

PMID- 18338690
TI  - Humoral response to rabies vaccines in pet dogs.
AB  - Humoral immune response was studied in dogs vaccinated with different tissue
      culture vaccines commonly used for immunization of dogs in India. The results
      revealed that after single dose of vaccination only 56% dogs developed protective
      titer (> or = 1:8). The response of the three vaccines used in the study was not
      similar, highlighting the need to maintain post marketing surveillance.

PMID- 18338691
TI  - Cytomegalovirus and rubella infection in children and pregnant mothers--a
      hospital based study.
AB  - Cytomegaloviruses (CMV) are ubiquitous and species-specific. Humans are believed
      to be the only reservoir of this virus and transmission occurs by direct or
      indirect person-to-person contact. Vertical transmission can lead to serious
      congenital infections. Rubella virus causes serious disease after vertical
      transmission but mostly remain subclinical or cause a trivial infection that may
      remain unrecognized. The objective of our study was to find the prevalence of CMV
      and rubella infection in the vulnerable section of our population attending GTB
      hospital. GroupI included pregnant women with bad obstetric history (BOH)
      (n=1115); GroupII normal pregnant women (n=500); Group III pediatric age group
      (n==585) and Group IV others with varied illness (n=100). Serologically IgM
      antibodies against CMV and rubella were detected using commercially available
      Elisa kit. The percentage prevalence in groupI was (11%) and (3.6%); groupII was
      (4%) and (0); groupIII was (12%) and (3%); group IV was (5%) and (1%) against CMV
      and rubella respectively. No apparent seasonal variation was observed in the
      pattern of infection. Also, overall infection rates were at a much lower rate as
      compared to other studies. Therefore the detection of IgM antibodies in early
      pregnancy is an important tool to identify active infection and to provide
      obstetric management to avoid the risk of congenital transmission of infection.
      This in turn may lead to a rethinking of current immunization strategies and
      appropriate modifications for the prevention of vertical infection.

PMID- 18338692
TI  - Histone as future drug target for malaria.
AB  - Malaria continues to be a major cause of mortality and morbidity in tropical
      countries and affecting around 100 countries of the world. As per WHO estimates,
      300-500 million are being infected and 1-3 million deaths annually due to
      malaria. With the emerging knowledge about genome sequence of all the three
      counterparts involved in the disease of malaria, the parasite Plasmodium, vector
      Anopheles and host Homo sapien have helped the scientists to understand
      interactions between them. Simultaneous advancement in technology further
      improves the prospects to discover new targets for vaccines and drugs. Though the
      malaria vaccine is still far away in this situation there is need to develop a
      potent and affordable drug(s). Histones are the key protein of chromatin and play
      an important role in DNA packaging, replication and gene expression. They also
      show frequent post-translation modifications. The specific combinations of these
      posttranslational modifications are thought to alter chromatin structure by
      forming epigenetic bar codes that specify either transient or heritable patterns
      of genome function. Chromatin regulators and upstream pathways are therefore seen
      as promising targets for development of therapeutic drugs.

PMID- 18338693
TI  - Influence of larval diet on the autogenous egg production in Phlebotomus papatasi
      (Diptera: Phlebotomidae) the vector of leishmanisis.

PMID- 18338694
TI  - Prevalence of RTIs/STDs amongst married women in the reproductive age group of
      (15-44 yrs) in a rural area of Distt. Sirmour (H.P.).

PMID- 18338695
TI  - Knowledge of STDs including HIV/AIDS amongst female adolescents in a rural area.

PMID- 18338696
TI  - Isospora belli infection in a malnourished child.
AB  - Isospora belli, a coccidian parasite usually causes a self limiting illness of
      acute onset with fever, diarrhoea and colicky pain in a normal host. In
      immunocompromised patients human isosporiasis becomes chronic. We report a case
      of a malnourished 9 year old female child who presented with complaints of loose
      stools, nausea, vomiting and weight loss for the past three months. Stool
      examination revealed immature oocysts of Isospora belli. The patient was
      successfully treated with TMP-SMX.

PMID- 18338697
TI  - Waste management: stepping up to the climate change challenge.

PMID- 18338698
TI  - Role of waste management with regard to climate protection: a case study.
AB  - According to the Kyoto Protocol and the burden-sharing agreement of the European
      Union, Austria is required to cut greenhouse gas (GHG) emissions during the years
      2008 to 2012 in order to achieve an average reduction of 13%, based on the level
      of emissions for the year 1990. The present contribution gives an overview of the
      history of GHG emission regulation in Austria and identifies the progress made
      towards the realization of the national climate strategy to attain the GHG
      emission targets. The contribution uses Austria as an example of the way in which
      proper waste management can help to reduce GHG emissions. The GHG inventories
      show that everything must be done to minimize the carbon input due to waste
      deposition at landfill sites. The incineration of waste is particularly helpful
      in reducing GHG emissions. The waste-to-energy by incineration plants and
      recovery of energy yield an ecologically proper treatment of waste using state-of
      the-art techniques of a very high standard. The potential for GHG reduction of
      conventional waste treatment technologies has been estimated by the authors. A
      growing number of waste incinerators and intensified co-incineration of waste in
      Austrian industry will both help to reduce national GHG emissions substantially.
      By increasing the number and capacity of plants for thermal treatment of waste
      the contribution of proper waste management to the national target for reduction
      of GHG emissions will be in the range of 8 to 14%. The GHG inventories also
      indicate that a potential CO2 reduction of about 500 000 t year(-1) is achievable
      by co-incineration of waste in Austrian industry.

PMID- 18338699
TI  - Mitigation of global greenhouse gas emissions from waste: conclusions and
      strategies from the Intergovernmental Panel on Climate Change (IPCC) Fourth
      Assessment Report. Working Group III (Mitigation).
AB  - Greenhouse gas (GHG) emissions from post-consumer waste and wastewater are a
      small contributor (about 3%) to total global anthropogenic GHG emissions.
      Emissions for 2004-2005 totalled 1.4 Gt CO2-eq year(-1) relative to total
      emissions from all sectors of 49 Gt CO2-eq year(-1) [including carbon dioxide
      (CO2), methane (CH4), nitrous oxide (N2O), and F-gases normalized according to
      their 100-year global warming potentials (GWP)]. The CH4 from landfills and
      wastewater collectively accounted for about 90% of waste sector emissions, or
      about 18% of global anthropogenic methane emissions (which were about 14% of the
      global total in 2004). Wastewater N2O and CO2 from the incineration of waste
      containing fossil carbon (plastics; synthetic textiles) are minor sources. Due to
      the wide range of mature technologies that can mitigate GHG emissions from waste
      and provide public health, environmental protection, and sustainable development
      co-benefits, existing waste management practices can provide effective mitigation
      of GHG emissions from this sector. Current mitigation technologies include
      landfill gas recovery, improved landfill practices, and engineered wastewater
      management. In addition, significant GHG generation is avoided through controlled
      composting, state-of-the-art incineration, and expanded sanitation coverage.
      Reduced waste generation and the exploitation of energy from waste (landfill gas,
      incineration, anaerobic digester biogas) produce an indirect reduction of GHG
      emissions through the conservation of raw materials, improved energy and resource
      efficiency, and fossil fuel avoidance. Flexible strategies and financial
      incentives can expand waste management options to achieve GHG mitigation goals;
      local technology decisions are influenced by a variety of factors such as waste
      quantity and characteristics, cost and financing issues, infrastructure
      requirements including available land area, collection and transport
      considerations, and regulatory constraints. Existing studies on mitigation
      potentials and costs for the waste sector tend to focus on landfill CH4 as the
      baseline. The commercial recovery of landfill CH4 as a source of renewable energy
      has been practised at full scale since 1975 and currently exceeds 105 Mt CO2-eq
      year(-1). Although landfill CH4 emissions from developed countries have been
      largely stabilized, emissions from developing countries are increasing as more
      controlled (anaerobic) landfilling practices are implemented; these emissions
      could be reduced by accelerating the introduction of engineered gas recovery,
      increasing rates of waste minimization and recycling, and implementing
      alternative waste management strategies provided they are affordable, effective,
      and sustainable. Aided by Kyoto mechanisms such as the Clean Development
      Mechanism (CDM) and Joint Implementation (JI), the total global economic
      mitigation potential for reducing waste sector emissions in 2030 is estimated to
      be > 1000 Mt CO2-eq (or 70% of estimated emissions) at costs below 100 US$ t(-1)
      CO2-eq year(-1). An estimated 20-30% of projected emissions for 2030 can be
      reduced at negative cost and 30-50% at costs < 20 US$ t(-) CO2-eq year(-1). As
      landfills produce CH4 for several decades, incineration and composting are
      complementary mitigation measures to landfill gas recovery in the short- to
      medium-term--at the present time, there are > 130 Mt waste year(-1) incinerated
      at more than 600 plants. Current uncertainties with respect to emissions and
      mitigation potentials could be reduced by more consistent national definitions,
      coordinated international data collection, standardized data analysis, field
      validation of models, and consistent application of life-cycle assessment tools
      inclusive of fossil fuel offsets.

PMID- 18338700
TI  - Biotic systems to mitigate landfill methane emissions.
AB  - Landfill gases produced during biological degradation of buried organic wastes
      include methane, which when released to the atmosphere, can contribute to global
      climate change. Increasing use of gas collection systems has reduced the risk of
      escaping methane emissions entering the atmosphere, but gas capture is not 100%
      efficient, and further, there are still many instances when gas collection
      systems are not used. Biotic methane mitigation systems exploit the propensity of
      some naturally occurring bacteria to oxidize methane. By providing optimum
      conditions for microbial habitation and efficiently routing landfill gases to
      where they are cultivated, a number of bio-based systems, such as interim or long
      term biocovers, passively or actively vented biofilters, biowindows and daily
      used biotarps, have been developed that can alone, or with gas collection,
      mitigate landfill methane emissions. This paper reviews the science that guides
      bio-based designs; summarizes experiences with the diverse natural or engineered
      substrates used in such systems; describes some of the studies and field trials
      being used to evaluate them; and discusses how they can be used for better
      landfill operation, capping, and aftercare.

PMID- 18338701
TI  - Green house gas emissions from composting and mechanical biological treatment.
AB  - In order to carry out life-cycle assessments as a basis for far-reaching
      decisions about environmentally sustainable waste treatment, it is important that
      the input data be reliable and sound. A comparison of the potential greenhouse
      gas (GHG) emissions associated with each solid waste treatment option is
      essential. This paper addresses GHG emissions from controlled composting
      processes. Some important methodological prerequisites for proper measurement and
      data interpretation are described, and a common scale and dimension of emission
      data are proposed so that data from different studies can be compared. A range of
      emission factors associated with home composting, open windrow composting,
      encapsulated composting systems with waste air treatment and mechanical
      biological waste treatment (MBT) are presented from our own investigations as
      well as from the literature. The composition of source materials along with
      process management issues such as aeration, mechanical agitation, moisture
      control and temperature regime are the most important factors controlling methane
      (CH4), nitrous oxide (N2O) and ammoniac (NH3) emissions. If ammoniac is not
      stripped during the initial rotting phase or eliminated by acid scrubber systems,
      biofiltration of waste air provides only limited GHG mitigation, since additional
      N2O may be synthesized during the oxidation of NH3, and only a small amount of
      CH4 degradation occurs in the biofilter. It is estimated that composting
      contributes very little to national GHG inventories generating only 0.01-0.06% of
      global emissions. This analysis does not include emissions from preceding or post
      treatment activities (such as collection, transport, energy consumption during
      processing and land spreading), so that for a full emissions account, emissions
      from these activities would need to be added to an analysis.

PMID- 18338702
TI  - The potential role of compost in reducing greenhouse gases.
AB  - The contribution of the agricultural sector to emissions of climate change gases
      is becoming better understood. At the same time, the potential role of the sector
      as a means through which to tackle climate change, widely neglected in the past,
      is becoming more widely acknowledged. The absorption potential of agricultural
      soils could contribute significantly to constraining growth in greenhouse gas
      emissions, while also contributing to improvements in soil quality in some areas.
      In addition to the measures listed above, other benefits of compost application
      may have some relevance. Some of these measures include replacement of chemical
      fertilizers (implying avoidance of greenhouse gases related to their production)
      reduced use of pesticides (avoiding emissions associated with their production),
      improved tilth and workability (less consumption of fuels). Typically, life-cycle
      analyses (LCAs) exhibit limitations related to assessing the effects of 'time
      limited' carbon sequestration in soils. This has tended to obscure the
      potentially important effect of composting, in which biogenic carbon is held in
      soils for a period of time before the carbon is released. The paper seeks to
      understand these effects and offers comments on the contribution of biological
      treatments to tackling climate change issues. Key issues include the replacement
      of fertilizers, reduction of N2O emissions, and peat replacement.

PMID- 18338703
TI  - Energy efficiency in waste-to-energy and its relevance with regard to climate
      control.
AB  - This article focuses on systematically highlighting the ways to optimize waste-to
      energy plants in terms of their energy efficiency as an indicator of the positive
      effect with regard to climate control. Potentials for increasing energy
      efficiency are identified and grouped into categories. The measures mentioned are
      illustrated by real-world examples. As an example, district cooling as a means
      for increasing energy efficiency in the district heating network of Vienna is
      described. Furthermore a scenario analysis shows the relevance of energy
      efficiency in waste management scenarios based on thermal treatment of waste with
      regard to climate control. The description is based on a model that comprises all
      relevant processes from the collection and transportation up to the thermal
      treatment of waste. The model has been applied for household-like commercial
      waste. The alternatives compared are a combined heat and power incinerator, which
      is being introduced in many places as an industrial utility boiler or in
      metropolitan areas where there is a demand for district heating and a classical
      municipal solid waste incinerator producing solely electrical power. For
      comparative purposes a direct landfilling scenario has been included in the
      scenario analysis. It is shown that the energy efficiency of thermal treatment
      facilities is crucial to the quantity of greenhouse gases emitted.

PMID- 18338704
TI  - Methods for determining the biomass content of waste.
AB  - As CO2 emission trading in Europe has been established it is of essential
      importance to distinguish between biogenic and fossil emissions. Emissions
      resulting from bio-fuels and biogenous fractions are categorized as climate
      neutral. Determination of plants using only fossil or bio-fuels is simple but
      categorization becomes more difficult for plants using a mix of fossil and bio
      fuel such as solid recovered fuels. In the meantime, different methods for
      solving this problem have been developed. Using different approaches and
      technologies, all of these methods have the same goal: determining the biomass
      content (biogenic fraction), for example, in solid recovered fuels or in the off
      gas of a mono- or co-incineration plant in order to calculate the biogenic carbon
      dioxide emissions. In the following article, the most common methods for
      determining the biogenic fraction of fuels, namely the Selective Dissolution
      Method, the Balance Method and the 14C-Method will be explained in detail.

PMID- 18338705
TI  - Hazardous waste incineration in context with carbon dioxide.
AB  - The Kyoto Protocol of 1997 demands an emission reduction of climate-affecting
      gases in various industrial sectors. In this context CO2 is one of the relevant
      gases and waste management is one of the relevant sectors. Referring to the
      situation in Europe, waste incineration is one of the major sources of CO2 in the
      waste management sector. The Kyoto Protocol, however, only covers CO2-emissions
      originating from fossil fuels, whereas the incineration of renewable materials,
      e.g. wood, is considered to be climate-neutral since it does not make any net
      contribution to the CO2 inventory of the atmosphere. Unlike the situation with
      municipal waste, there is little if any information on the CO2-emissions caused
      by the incineration of hazardous waste in specialized plants, and the renewable
      fraction in these materials. The present paper focuses on this gap of knowledge.
      Taking the full-scale hazardous waste incineration plant in Biebesheim, Germany,
      as an example, a carbon balance was set up for the whole-plant taking into
      account all other material flows. Afterwards the determination of the proportion
      of renewable materials in the hazardous waste incinerated by means of the
      radiocarbon method (14C) is reported. On the basis of the results, optimization
      potentials are discussed.

PMID- 18338706
TI  - Environmental assessment of waste incineration in a life-cycle-perspective
      (EASEWASTE).
AB  - A model for life-cycle assessment of waste incinerators is described and applied
      to a case study for illustrative purposes. As life-cycle thinking becomes more
      integrated into waste management, quantitative tools for assessing waste
      management technologies are needed. The presented model is a module in the life
      cycle assessment model EASEWASTE. The module accounts for all uses of materials
      and energy and credits the incinerator for electricity and heat recovered. The
      energy recovered is defined by the user as a percentage of the energy produced,
      calculated on the lower heating value of the wet waste incinerated. Emissions are
      either process-specific (related to the amount of waste incinerated) or input
      specific (related to the composition of the waste incinerated), while mass
      transfer to solid outputs are governed by transfer coefficients specified by the
      user. The waste input is defined by 48 material fractions and their chemical
      composition. The model was used to quantify the environmental performance of the
      incineration plant in Aarhus, Denmark before and after its upgrading in terms of
      improved flue gas cleaning and energy recovery. It demonstrated its usefulness in
      identifying the various processes and substances that contributed to
      environmental loadings as well as to environmental savings. The model was
      instrumental in demonstrating the importance of the energy recovery system not
      only for electricity but also heat from the incinerator.

PMID- 18338707
TI  - Clean development mechanism: an incentive for waste management projects?
AB  - The Clean Development Mechanism (CDM) was introduced by the Kyoto Protocol to
      provide a financial incentive to establish project activities in developing
      countries for reducing greenhouse gas emissions while also fostering sustainable
      development. This article shows that waste management project activities play an
      important role in achieving the aims of the CDM. It describes how these
      activities have to prove additionality, how the emission reductions must be
      calculated and monitored in order to be eligible and in order to lead to
      Certified Emission Reductions (CERs). The article further provides an analysis
      about the various challenges that are involved in applying the CDM scheme to
      waste management project activities, which require a new specific set of
      technical skills and regulatory standards.

PMID- 18338708
TI  - Exploring the clean development mechanism: Malaysian case study.
AB  - During 2006 the CDM market in Malaysia became established and by December 2007 a
      total of 20 Malaysian projects had registered with the CDM Executive Board. The
      Kyoto Protocol defines the Annex 1 countries, as countries that are obliged to
      reduce their greenhouse gas (GHG) emissions and the clean development mechanism
      (CDM) allows Annex 1 countries to develop projects, which contribute to emission
      reduction, in non-Annex 1 (developing) countries. Currently, two projects have
      been corrected due to request for review and there is one project for which
      review is requested. Two projects have been rejected by the Executive Board. The
      broad knowledge of CDM in Malaysia and the number of successful projects are
      partly due to the well-functioning CDM institutional framework in Malaysia. As an
      illustration this article focuses on a Malaysian-Danish project and describes the
      implementation of CDM in Malaysia and refers to this specific project. The
      project was registered with the CDM Executive Board in May 2007 and is a methane
      avoidance project in which methane is captured from a landfill and used to
      generate electricity.

PMID- 18338709
TI  - Simultaneous detection of Neisseria gonorrhoeae and Chlamydia trachomatis by PCR
      in genitourinary specimens from men and women attending an STD clinic.
AB  - Neisseria gonorrhoeae and Chlamydia trachomatis are the two most common bacterial
      sexually transmitted infections that manifest primarily as urethritis in males
      and endocervicitis in females, though the infection may be asymptomatic
      especially in women. Since complications may occur in untreated symptomatic and
      asymptomatic infected individuals, early diagnosis and treatment of infected
      individuals is required to prevent severe sequelae and spread of these diseases.
      Recently molecular amplification assays like Polymerase Chain Reaction (PCR) and
      Ligase Chain Reaction (LCR) have been found to be highly sensitive and specific
      methods for detection of N. gonorrhoeae and C. trachonmatis not only in urethral
      and cervical specimens but also in urine. The objective of this study was to
      screen male and female Sexually Transmitted Disease (STD) clinic attenders, with
      and without symptoms suggestive of urethritis and cervicitis for presence of N.
      gonorrhoeae and C. trachomatis using a multiplex PCR based assay, to compare its
      performance with culture for N. gonorrhoeae and Direct Fluorescent Antibody (DFA)
      staining for C. trachomatis and also to compare the efficacy of PCR test
      performed on urine and genital swab specimens collected from this high risk
      group. Genital specimens and urine was collected from STD clinic attenders. N.
      gonorrhoeae and C. trachomatis was detected in genital specimens by culture and
      DFA respectively. Multiplex PCR was used to detect N. gonorrhoeae and C.
      trachomatis infection in both genital and urine specimens. Among men with
      urethritis, N. gonorrhoeae was detected in 70% by culture and 77% by PCR, while
      C. trachomatis as detected in 7.5% by DFA and 17.5% by PCR. Among females with
      endocervicitis, N. gonorrhoeae was detected in 7.7% by culture and 30.7% by PCR,
      while C. trachomatis was detected in 7.7% by DFA and in 15.4% by PCR. None of the
      asymptomatic males were positive for N. gonorrhoeae and C. trachomatis by
      conventional methods, while 43.9% were positive for N. gonorrhoeae and 7.5% for
      C. trachomatis by PCR. Fifty per cent of asymptomatic women were positive for C.
      trachomatis by PCR alone. We encountered PCR positive but culture/DFA negative
      results and also PCR negative but culture/DFA positive results. In view of this a
      single PCR test cannot be used for diagnosis and treatment of N. gonorrhoeae and
      C. trachomatis infection unless confirmed by a second test.

PMID- 18338710
TI  - Nonparametric estimation of survival function of HIV+ patients with doubly
      censored data.
AB  - In the analysis of follow-up studies of patients who have been or may be infected
      by the Type-1 human immunodeficiency virus (HIV-1), which causes the acquired
      immune deficiency syndrome (AIDS), one problem of interest is the estimation of
      distribution of the survival function when the origin and end points defining the
      survival time suffer interval censoring. In this paper, we have compared Kaplan
      Meier, midpoint estimation and sun (1997), by analysis of a cohort study data of
      Iranian Injecting Drug Users (IDU) who became HIV infected through the using
      common infected syringe.

PMID- 18338711
TI  - Human immunodeficiency virus type-1 (HIV-1) and the associated clinical features
      among sero-positive Nigerian subjects.
AB  - Enzyme Linked Immunosorbent Assay (ELISA) and Westernblot were employed to
      analyze sera collected from one thousand and fifty (1050) patients who tested HIV
      positive type-1. Out of this, 95 (9.1%) of the patients were less than 2 years
      old, 102 (10.0%) were aged between 2-15 years old while 813 (77.4%) were aged
      above 15 years. For any age group, the ratio of male to female was 1:1 except
      that there was excess of males below 5 years. There were four (4) most frequent
      signs and symptoms observed. These were loss of weight or malnutrition,
      generalized lymphadenopathy, chronic watery diarrhoea and chronic chest
      infections. Loss of weight was recorded in 65.0% of the seropositive patients in
      all age groups. Generalized lymphadenopathy was seen in 35.0% of all the age
      groups but was most frequent in 36.1% of those less than 2 years. Chronic watery
      diarrhoea (42.8%) was frequent in patients less than 2 years and less frequent in
      18.0% of older children between 1-15 years. Chronic chest infections were least
      frequent in 25.0% of adults above 15 years old and highest frequency was observed
      in 53.0%, children less than 2 years. Forty patients had incomplete
      documentations and children of pediatric ages had acutely overt clinical
      manifestation of HIV (1&11) attributable to undeveloped immune competence.

PMID- 18338712
TI  - Pattern of hepatitis C virus genotypes in HIV infected patients in RIMS,
      Hospital, Imphal, Manipur.
AB  - The present study was carried out to find the pattern of genotype distribution of
      Hepatitis C virus. Twenty-three Hepatitis C virus positive serum samples in
      various age-groups of both sexes attending, Microbiology Department, RIMS during
      the period from September 2002 to December 2004 were studied for Hepatitis C
      genotype. These HCV positive serum samples were sent to National Institute of
      Cholera and Enteric Diseases, Kolkata. The serum samples were tested for HCV-RNA
      by qualitative RT-PCR test and then genotyped by type specific RT-PCR. Out of 23
      serum samples, 22 were males. All the 23 HCV positive serum samples were also
      tested positive for HCV-RNA by qualitative RT-PCR. Majority of the cases belonged
      to the age group of 31-40 years. Higher percentage of Hepatitis C cases were
      Injecting Drug Users and next to it were patients with multiple sexual contacts.
      Among the IDUs, Hepatitis C virus 3a type was the commonest genotype (61.1%)
      followed by 1b (22.2%) and 3b (16.7%) respectively. Hepatitis C genotype 3a was
      predominant (52.2%) followed by 1b (26%) and 3b (21.8%). HCV genotype 3a occurred
      most commonly in the age group of 21-40 years.

PMID- 18338713
TI  - Chikungunya viral disease in district Bhilwara (Rajasthan) India.
AB  - An investigation of chikungunya outbreak cases was carried out in Bhilwara
      District, Rajasthan during Aug-Sep 2006. Fever with multiple joint pains was the
      first presenting feature. Aedes larval surveys indicate high Breteau index (78.6
      to 200), House index (48.0 to 83.3) & Container index (41.1 to 73.6) above the
      critical index. Out of 40 sera samples tested, 12 showed HI antibodies for
      chikungunya virus in high titres and another five were positive for IgM
      antibodies against chikungunya. The clinico-epidemiological, laboratory and
      entomological investigations confirm that this episode of fever was due to
      chikungunya fever. Strengthening and intensification of surveillance along with
      educating the community were recommended for control of outbreak.

PMID- 18338714
TI  - Clinico-epidemiological profile of fever cases admitted during epidemics of
      Chikungunya fever.
AB  - A study of Clinico-epidemiological profile of fever cases admitted during
      epidemics of Chikungunya fever was carried out in Latur city of Maharashtra
      State. A total of 238 fever cases were investigated in relation to clinico
      epidemilogical characteristics. Maximum fever cases admitted during epidemics of
      Chikungunya fever were in the age group 16-60 years (74.8%). There was no sex
      predominance. The commonest symptoms of admitted fever cases were sudden onset of
      high-grade fever (99.5%), followed by joint pains with tenderness on examination
      (90.7%), headache (58.4%) and body ache (23.5%). Average duration of illness was
      3.01 days (S.D.=0.38). There was no mortality among affected fever cases. Family
      or neighborhood clustering of cases was observed in 66.8% and 31.5% of the cases
      respectively. The important environmental factors were presence of open water
      tank in the house (68%), infrequent cleaning and drying of non drinking water
      containers (once in 11 days) and abundance of mosquitoes in the house. (45.7%).

PMID- 18338715
TI  - Chikungunya epidemic: global and Indian scenario.
AB  - Chikungunya is a disease of zoonotic importance affecting man with non-human
      primates as a main reservoir. Recently the world has seen its outbreaks in Asia
      and Africa affecting large population. The disease has re-emerged after 2 long
      decades. Other part of the world reported it as a disease which is introduced
      through travelers. The known vectors of Chikungunya are Aedes mosquitoes, notably
      Aedes aegypti and A. albopiticus. Although, the people of rural areas are among
      more risk groups, the disease spread very rapidly among urban population. The
      disease shows epidemic pattern with severe arthralgia and usually without any
      mortality but in the recent outbreak it has shown mortality also. Thus it is the
      major cause of public health concern. Understanding the public health
      significance of disease, there is a need of continuous monitoring and
      surveillance of the virus in both human and animal population.

PMID- 18338716
TI  - Socio-demographic profile of leprosy patients in two districts of western Uttar
      Pradesh.
AB  - Despite achieving the goal of national elimination of leprosy, it remains a
      serious public health problem in the high prevalence states of Uttar Pradesh,
      Bihar and Orissa. A significant percentage of newly detected cases are
      Multibacillary. It underscores the importance of developing a more effective
      strategy to combat the disease in high prevalence pockets of the country. A
      glance into sociodemographic profile of the leprosy patients of one the high
      prevalence states might help in understanding the current ground situation
      better. A questionnaire based study was conducted at health care center of two
      districts of Uttar Pradesh (Rampur and Moradabad). Data on demographic profile of
      leprosy patients attending these centers were collected. The leprosy patients
      were more frequently males (63.8%). The duration of time before presentation was
      significantly longer for semiskilled workers (Kuppuswami Scale classification), p
      = 0.029. Patients with multibacillary disease were younger (mean age 31.04 yrs)
      as compared to paucibacillary leprosy (mean age 38.7yrs), p value = 0.041. These
      observations suggests that a specific population based approach is required to
      detect new cases early. Certain groups of the population might benefit from
      active surveillance.

PMID- 18338717
TI  - Study on the factors affecting the MDA programme in Kerala state.
AB  - The Mass Annual Single dose DEC administration (MDA) was initiated in India from
      1997. In Kerala MDA was studied as a pilot project in Alappuzha and Kozhikode
      District from 2000-04 and the first round of MDA was launched in Kerala covering
      eleven endemic districts, in March 2005. On evaluation, the drug distribution
      coverage, compliance, etc. were found to be not satisfactory and a need to elicit
      the factors for poor performance of MDA is felt essential. The main reasons for
      poor performance of MDA in Kerala state were the lack of adequate prior
      information to the target population regarding the importance LF elimination
      programme and inadequate awareness. The fear of side reactions, antipropagonda,
      poor IEC activities repeated postponement of programme, insufficient time for
      mobilisation etc. were the other reasons for poor compliance. The purpose of the
      present study was to bring the observations to the notice of the authorities so
      that appropriate remedial measures are incorporated.

PMID- 18338718
TI  - Treatment seeking behaviour of malaria patients in desert part of Rajasthan,
      India.
AB  - Malaria remains to be the most important cause of morbidity and mortality in
      India and in many other tropical countries with approximately 2 to 3 million new
      cases arising every year. In spite of arid conditions prevailing in desert part
      of Rajasthan, malaria is a major public health problem. A longitudinal study on
      social determinants of malaria has been undertaken in different villages of
      Ramgarh PHC of Jaisalmer district, Rajasthan. The study aims to know treatment
      seeking behabiour of malaria patients in the desert communities which is
      significantly different than the non-desert part of India. Out of 60 villages, 12
      villages and 573 malaria patients were selected randomly. Interview technique was
      used for data collection. Information was recorded on pre-tested schedules. Self
      diagnosis 423 (73.8%) was more common among the respondents and 443 (77.3%) had
      taken treatment at home with local herbal remedies as the first treatment action.
      Desert population was not used to laboratory test for the malaria diagnosis.
      Symptoms based treatment was practised. They used private and government health
      facilities for the treatment of malaria. Self diagnosis for malaria was common
      but practised more by the poorer households. A large part of the population did
      not complete the full course of malaria treatment as a result drug resistance was
      more common. They did not use the government health facility as a first step of
      malaria treatment. There is need for health education with campaign emphasizing
      the role of mosquitoes in malaria transmission and the need for prompt medical
      intervention. The use of Government health services for the diagnosis and
      treatment of malaria by the poor should be encouraged through appropriate
      information, education and communication (IEC) which on the long run will be more
      cost effective for desert population under the national malaria control
      programme.

PMID- 18338719
TI  - Treatment practices for lymphatic filariasis amongst doctors of East Godavari
      District, Andhra Pradesh.

PMID- 18338720
TI  - Sero-prevalence of Dengue infection in Lucknow.

PMID- 18338721
TI  - Potential of urban agriculture: benefits and risks.

PMID- 18338722
TI  - Overview on urban and peri-urban agriculture: definition, impact on human health,
      constraints and policy issues.
AB  - OBJECTIVES: To collate and synthesize current knowledge of components of urban
      agriculture (UA) with a thematic emphasis on human health impact and a geographic
      emphasis on East Africa. DATA SOURCES: Data management followed a structured
      approach in which key issues were first identified and then studies selected
      through literature search and personal communication. DATA EXTRACTION: Evidence
      based principles. DATA SYNTHESIS: Urban agriculture is an important source of
      food security for urban dwellers in East Africa. Descriptors of UA are location,
      areas, activities, scale, products, destinations, stakeholders and motivation.
      Many zoonotic and food-borne diseases have been associated with UA but evidence
      on human health impact and management is lacking. Major constraints to UA are
      illegality and lack of access to input and market; policy options have been
      developed for overcoming these. CONCLUSION: Urban agriculture is an important
      activity and likely to remain so. Both positive and negative human health impacts
      are potentially important but more research is needed to understand these and set
      appropriate policy and support levels.

PMID- 18338723
TI  - Gender, perceptions and behaviour towards health risks associated with urban
      dairy farming in Dagoretti Division, Nairobi, Kenya.
AB  - OBJECTIVES: To determine the socio-cultural, economic and environmental factors
      that encourage urban dairy production and the factors which may predispose the
      producer, consumer and other handlers to risks associated with dairy farming. To
      assess the knowledge, attitudes and behaviour of men and women towards health
      risks and benefits associated with urban dairy farming in smallholder dairy
      farming and their immediate non-dairy farming neighbour households. DESIGN: A
      cross sectional study and participatory urban appraisal (PUA. SETTING: Urban and
      peri-urban households in Dagoretti Division, Nairobi. SUBJECTS: Three hundred
      dairy farming households, and 150 non-dairy farming neighbour households and six
      participatory urban appraisals, 58 males and 45 females. RESULTS: There were more
      females than males dairy farmers. Both women and men had equal access to
      resources and benefits obtained from dairy farming but the men had the greater
      control over the resources. Low levels of knowledge on the specific health risks
      related to urban dairy farming were observed. Less than half of the respondents
      believed they were at risk of being exposed to the health hazards, while 63%
      sensed they could protect themselves from the health risks. There was an
      association between knowledge levels, perceptions and behaviour of men and women
      toward risks associated with dairy farming. CONCLUSIONS: Apart from giving
      treatment to animals most men did less dairy farming activities. Women rated men
      lower in all dairy activities but when the men did the scoring for the same
      activities they rated themselves higher, arguing that their participation was
      indirect such as providing cash to buy the feed supplements and veterinary
      services. There were gender differences in all important tasks associated with
      dairy keeping. Farmers stated that older children, when not in school sometimes
      assisted but in general children did not show much enthusiasm in dairy work.

PMID- 18338724
TI  - Isolation of E. coli O157:H7 from milk and cattle faeces from urban dairy farming
      and non dairy farming neighbour households in Dagoretti Division, Nairobi, Kenya:
      prevalence and risk factors.
AB  - OBJECTIVE: To estimate the prevalence of E. coli O157:H7 in milk and cattle
      faecal samples dairy and non dairy neighbouring households and to relate this
      prevalence to the risk to human health. DESIGN: Cross sectional study. SETTING:
      Urban and peri-urban households of Dagoretti, Division, Nairobi, Kenya. SUBJECTS:
      Dairy farming households and non dairy farming neighbouring households. RESULTS:
      E coli O157:H7 was isolated from milk samples at three of 136 non-dairy neighbour
      households (2.2% C.I. 0.5%,6.3%) but was not found in any of the milk samples
      from the 260 milk samples from dairy households (0% C.I. 0.0%,1.4%). E.coli
      O157:H7 was also found in fifteen of 285 pooled household cattle faecal sample
      (5.2%, C.I. 3.1%, 8.7%). One of the faecal isolates was found to have the marker
      for the production of VT1. Discussions with focus groups revealed that the
      participants had limited knowledge about E. coli O157:H7. Focus group discussions
      and household questionnaires revealed practices increasing risk of E. coli
      infections to humans are associated with milking hygiene, drinking water source
      and treatment, and manure handling. CONCLUSIONS: E. coli O157:H7 exists in urban
      setting and continuous surveillance is needed in case conditions and practices
      change favoring an increase in its prevalence and transmission to people.

PMID- 18338725
TI  - Investigation into the prevalence of bovine cryptosporidiosis among small-holder
      dairy households in Dagoretti Division, Nairobi, Kenya.
AB  - OBJECTIVES: To determine the prevalence of bovine cryptosporidiosis and knowledge
      of this disease among smallholder dairy households in Dagoretti Division,
      Nairobi, Kenya. DESIGN: Cross-sectional survey of 299 dairy households and 149
      non-dairy neighbouring households. SETTING: Dagoretti Division, a mixed urban and
      peri-urban area of Nairobi. SUBJECTS: Dairy householders and their immediate, non
      cattle keeping neighbours. RESULTS: There were 50 positive households from 285
      households where a fecal sample was collected giving an apparent prevalence of
      18% [13, 23]%. Positive households were positively associated with watering
      cattle with well water, presence of shallow well, cemented cattle shed flooring
      and number of household cattle. (p < 0.05) Knowledge of cryptosporidiosis was
      generally low with more dairy respondents, 19% (56/292), who said they had heard
      of the disease than their non-dairy neighbours, 4% (6/146). CONCLUSION: This 18%
      bovine cryptosporidiosis prevalence does not constitute a risk to human health
      unless Cryptosporidium parvum is present. Typing of these positive samples is
      needed to assist in accurately determining the risk and enable evidence based
      management of urban dairy farming.

PMID- 18338726
TI  - Prevalence of aflatoxin M1 and B1 in milk and animal feeds from urban smallholder
      dairy production in Dagoretti Division, Nairobi, Kenya.
AB  - OBJECTIVE: To estimate the prevalence of Aflatoxin M1 and Total Aflatoxin B1 in
      milk and animal feeds. DESIGN: Cross sectional household study. SETTING: Urban
      and peri-urban area of Dagoretti Division, Nairobi, Kenya. SUBJECTS: Two hundred
      fifty seven dairy farming households and 134 non-dairy neighbouring households.
      RESULTS: The prevalence of AFM1 in milk was found to be 45.5% (178/391). The
      farmer prevalence was 43.5% (112/257), while that of non-farmer was 49.2% (66/
      134). There was however no statistical significant difference between the two
      categories. Of the 178 positive milk samples, 49% had aflatoxin levels exceeding
      0.05 microg Kg(-1). The prevalence of AFB1 in the feed was found to be 98.6%
      (69/70) with 83% of the samples having aflatoxin B1 levels exceeding 10 microg
      Kg(-1). Only one feed sample had no traces of AFB1. CONCLUSION: This study points
      to an underlying problem that requires the action by policy makers, considering
      the number of samples with aflatoxin M1 [49%] and aflatoxin B1 [83%] exceeding
      the WHO/FAO tolerance limits for milk and feeds destined for dairy animals.

PMID- 18338727
TI  - Investigation on the prevalence of antimicrobial residues in milk obtained from
      urban smallholder dairy and non-dairy farming households in Dagoretti Division,
      Nairobi, Kenya.
AB  - OBJECTIVES: To assess the prevalence and the level of awareness of the risk posed
      by antibiotic residues among the urban dairy and non-dairy farming households
      using a household survey and laboratory analysis of milk samples. DESIGN: A cross
      sectional study. SETTING: Urban small holder dairy farming and non-farming
      households in Dagoretti division, Nairobi. RESULTS: The prevalence of antibiotic
      residues in dairy household milk samples was 4% (11/259) and in milk samples from
      non-dairy neighbouring households the prevalence was 0.07% (1/136). One sample
      was detected to belong to beta lactam and one to the tetracycline group of
      antibiotics. The remaining 10 were not categorised. Approximately 20% of dairy
      and non-dairy respondents were unsure of the risk that may be posed by the
      presence of antibiotic residues in milk. A high proportion of the respondents
      said they would be able to protect themselves from risk posed by antibiotic
      residues by following advice given by veterinary officers on the withdrawal
      periods after treatment of animals. CONCLUSION: Education of the farmers,
      continuous surveillance and understanding of the socio-economic incentives that
      would be traded off at farm level would help to reduce or eliminate the risk
      posed by the residues in marketed or consumed milk.

PMID- 18338728
TI  - Investigation of the prevalence of bovine tuberculosis and risk factors for human
      infection with bovine tuberculosis among dairy and non-dairy farming neighbour
      households in Dagoretti Division, Nairobi, Kenya.
AB  - OBJECTIVE: To determine the prevalence of bovine tuberculosis in urban dairy
      cattle and examine possible risk factors for human infection with bovine
      tuberculosis (BTB). DESIGN: Cross sectional study. SETTING: Urban and peri-urban
      dairy and non-dairy farming neighbour households. SUBJECTS: One hundred forty
      three dairy cattle and 299 and 149 dairy and non-dairy neighbour households
      respectively. RESULTS: Ten percent of the animals (15/143) were found to be
      reactors to the tuberculin test. The majority of the respondents 57% (168/295)
      and 72% (106/147) in dairy farming and non-farming households respectively, had
      limited knowledge of the disease in cattle thus making them unable to adopt any
      precautionary measures to protect themselves from contracting bovine
      tuberculosis. Distance from the main house and cattle shed, the time spent
      attending to the cattle, (on average 4.8 hours), and making of traditionally
      fermented milk were considered to be the major risk factors. CONCLUSION: Due to
      the presumed high background prevalence of human tuberculosis, the specificity of
      the test employed was unknown. Therefore no definite estimate of the prevalence
      of BTB was made. It is therefore necessary for further investigation involving
      culture, isolation and molecular typing from reactors to establish the prevalence
      of M. bovis in this setting.

PMID- 18338729
TI  - Investigations into the prevalence of bovine brucellosis and the risk factors
      that predispose humans to infection among urban dairy and non-dairy farming
      households in Dagoretti Division, Nairobi, Kenya.
AB  - OBJECTIVE: To explore the knowledge, attitudes and practices of dairy and non
      dairy farming households in Dagoretti in regard to the risk posed by bovine
      brucellosis and determine the prevalence of the disease in urban dairy cattle.
      DESIGN: A cross sectional study. SETTING: Urban and Peri-urban dairy farming and
      non dairy farming households in Dagoretti division, Nairobi. SUBJECTS: Two
      hundred ninety nine dairy farming and 149 non dairy farming households.
      INTERVENTION: Segregated focus group discussions, administration of a household
      questionnaire and collection of unboiled milk from dairy and non dairy farming
      households were the instruments used to gather data on the practices, attitudes,
      perceptions and prevalence of bovine brucellosis. RESULTS: Three hundred and
      ninety three milk samples were collected and analysed for the presence of
      antibodies to Brucella abortus in an indirect ELISA. The apparent prevalence of
      bovine brucellosis from milk was estimated at 1% for the samples collected while
      in dairy farming households the prevalence was 1.1% [0.2, 3.4%] and 0.7% [0.4%]
      in non dairy farming households.. Thirty percent (90/296) of dairy respondents
      and 22% (32/147) of non-dairy respondents knew of the existence of brucellosis.
      Risk of contracting brucellosis was very low considering that milk is boiled
      together with other ingredients used in making tea and porridge. However, 31%
      (93/296) and 22% (31/143) of dairy and non dairy farming households respectively
      made traditionally fermented milk without first boiling the milk. This practice
      may predispose this group to brucellosis. CONCLUSION: The low prevalence of
      bovine brucellosis requires constant surveillance in case the prevalence rates do
      change. Education of dairy farming households who are more at risk of contracting
      brucellosis on the transmission pathways and risk factors is required in order to
      lower further the prevalence of bovine brucellosis in Dagoretti.

PMID- 18338730
TI  - Sticking to the recipe. Develop one program with basic guidelines for improving
      care, effectiveness without overwhelming providers, the IOM says.
AB  - The IOM's call for a national initiative to determine best medical practices has
      some wondering how such an effort would work. But most everyone agrees that
      providers and payers are overwhelmed by data about clinical effectiveness. "Once
      we get an innovation, let's study it right away so we can be sure every person
      who could benefit gets it, or if it doesn't work, let's do no harm," says
      WellPoint's Samuel Nussbaum, left.

PMID- 18338731
TI  - Mass. Blues floats flat-fee plan.

PMID- 18338732
TI  - Managed-care CMOs lead pack.

PMID- 18338733
TI  - Let the sunshine in. Medical errors should be the start of a process, not
      something to bury.

PMID- 18338735
TI  - Reform is no 'either-or'. We must fix the payment system along with access.

PMID- 18338734
TI  - Private-public mix is a match. Survey reveals that many healthcare experts side
      with the Democrats' approach to reform, but costs remain an issue.

PMID- 18338736
TI  - ACHE Young Executive of the Year. 'Opportunity of a lifetime'.

PMID- 18338738
TI  - Happiness: enough already.

PMID- 18338737
TI  - ACHE Gold Medal Award. Leader and educator.

PMID- 18338739
TI  - Man makes life.

PMID- 18338740
TI  - Work out and drink up.

PMID- 18338741
TI  - Death at the Army's hands.

PMID- 18338742
TI  - Little athletes, big injuries. Kids suffer when coaches and parents pile on too
      much training. What to watch for.

PMID- 18338743
TI  - Use of a topical emulsion for wound healing.
AB  - Treatment of skin trauma following removal of actinic keratoses and skin cancer
      lesions and following radiation therapy for breast cancer is an often under
      treated problem compared to the primary condition. However, skin trauma can cause
      patients significant discomfort, pain, and loss of quality of life. Palliative
      treatments such as lotions and ointments may help soothe the skin trauma, but
      helping the healing process is the best way to treat the wound and relieve
      patients of their discomfort. In clinical trials, the use of Biafine, a topical
      emulsion, promoted wound healing following these clinical situations by
      increasing the number of macrophages recruited to a wound and thus enhancing
      healing. This topical emulsion has also been proven to be soothing for the
      patient. This review will discuss the molecular mechanisms of wound healing and
      the uses of Biafine in the treatment of skin damage caused by procedures for
      various conditions such as actinic keratosis, skin cancer lesions, and radiation
      dermatitis.

PMID- 18338744
TI  - Molecular basis explanation for imatinib resistance of BCR-ABL due to T315I and P
      loop mutations from molecular dynamics simulations.
AB  - BACKGROUND: Computational simulations have become powerful tools for
      understanding detailed interactions in biologic systems. To the authors'
      knowledge to date, the mechanism of imatinib resistance in BCR-ABL has not been
      clarified at the atomic level, and computational studies are required. METHODS:
      Molecular dynamics (MD) simulations on the complex of imatinib with the wild
      type, T315I mutant, and 10 other P-loop mutants of the tyrosine kinase BCR-ABL
      were performed to study the mechanism of imatinib resistance. RESULTS:
      Simulations suggested that imatinib resistance of T315I results mainly comes from
      the breakdown of interactions between imatinib and both E286 and M290,
      contradictory to what was believed previously, in that the missing hydrogen
      bonding is the main contribution. The current results also demonstrated that the
      unfavorable electrostatic interaction between P-loop and imatinib is the main
      reason for resistance for the P-loop mutations. Furthermore, in Y253H,
      protonation of the histidine at the epsilon position is essential for rendering
      this mutation resistant to imatinib. CONCLUSIONS: The current results indicated
      that large-scale simulations may offer insight and information that other simple
      modeling methods cannot provide regarding the problem of BCR-ABL imatinib
      resistance, especially in the case of conformational changes because of remote
      mutations. Imatinib resistance mechanisms that were not anticipated previously
      were revealed by analyzing the interactions between imatinib and individual
      residues based on simulation results. This results demonstrated that MD is a
      powerful way to verify and predict the clinical response or resistance to
      imatinib and to other potential drugs.

PMID- 18338745
TI  - Prednisone, etoposide, procarbazine, and cyclophosphamide (PEP-C) oral
      combination chemotherapy regimen for recurring/refractory lymphoma: low-dose
      metronomic, multidrug therapy.
AB  - BACKGROUND: Many patients with recurrent lymphoma are unable to tolerate
      intensive therapies, or have disease that is refractory. Metronomic chemotherapy
      offers a novel, potentially less toxic yet effective treatment strategy. METHODS:
      An analysis was performed on 75 lymphoma patients who were treated with the PEP-C
      regimen at a single institution. The program consisted of oral prednisone 20 mg
      after breakfast, cyclophosphamide 50 mg after lunch, etoposide 50 mg after
      dinner, and procarbazine 50 mg at bedtime with an oral antiemetic. All
      medications were administered daily until the white blood cell count fell to less
      than 3.0 x 10(9)/L, whereupon treatment was withheld until recovery from the
      nadir. Therapy was then reinstituted on a daily, alternate day, or fractionated
      weekly basis (eg, 5 of 7 days), depending on patient tolerance. Doses given per
      day were held constant. RESULTS: Eighty percent of patients had previously
      received 2 or more treatments. Overall, 69% achieved an objective response after
      PEP-C treatment, with 36% complete responses and 33% partial responses. Subjects
      with indolent histologies had superior overall responses, complete responses, and
      time on therapy relative to those with aggressive histologies. The regimen was
      generally well tolerated. CONCLUSIONS: Metronomic therapy with low-dose oral
      agents administered in combination for continuous, prolonged periods with minimal
      drug-free intervals represents a novel, active, easily tolerated approach to
      management of patients with recurrent lymphoma, particularly those with indolent
      histologies.

PMID- 18338746
TI  - Emotional well-being does not predict survival in head and neck cancer patients:
      a Radiation Therapy Oncology Group study.

PMID- 18338748
TI  - Antioxidant profiles of a prepared extract of Chinese herbs for the treatment of
      atopic eczema.
AB  - A standardized mixture of Chinese herbs, Zemaphyte taken orally as a daily
      decoction has been shown to be effective in the treatment of atopic eczema. This
      study showed that Zemaphyte is an efficient antioxidant, being capable of
      scavenging both superoxide and hydroxyl, and preventing peroxidation of
      biological membranes. It does not degrade hydrogen peroxide directly, but instead
      most likely forms a Zemaphyte-hydrogen peroxide complex. The complexed hydrogen
      peroxide can then be degraded in the presence of catalase to form oxygen and
      water. It is conceivable that Zemaphyte may contribute to the down-regulation of
      the activities of cells implicated in atopic eczema through its antioxidant
      activities.

PMID- 18338749
TI  - 1H and 13C NMR assignments for 6-demethylvermistatin and two penicillide
      derivatives from the mangrove fungus Guignardia sp. (No. 4382) from the South
      China Sea.
AB  - One new compound 6-demethylvermistatin (1), together with two known compounds,
      the penicillide derivatives (2) and (3) were isolated from the mangrove fungus
      Guignardia sp. No. 4382 obtained from the South China Sea. Their structures were
      assigned using high-resolution electron ionization mass spectrometry(HREIMS),
      (1)H and (13)C NMR spectra, DEPT, and by 2D COSY, HMQC, and HMBC experiments. The
      absolute configuration of 1 was established by comparison of its CD with that of
      vermistatin.

PMID- 18338750
TI  - Adiponectin blocks multiple signaling cascades associated with leptin-induced
      cell proliferation in Apc Min/+ colon epithelial cells.
AB  - We previously demonstrated that leptin, an adipose-derived hormone, induces cell
      proliferation in a model of preneoplastic (IMCE (Apc(Min/+)), but not normal
      (YAMC (Apc(+/+)), colon epithelial cells by inducing autocrine IL-6 production
      and trans-IL-6 signaling. Low serum adiponectin is associated with colon,
      prostate and breast cancer. Adiponectin is secreted by white adipose tissue; the
      levels of adiponectin in the blood decrease as body mass index (and leptin)
      increases. In our study, we tested whether murine recombinant globular
      adiponectin (gArcp30) could modulate leptin-induced cell proliferation, autocrine
      IL-6 production, trans-IL-6 signaling and other leptin-induced cell signaling
      events previously observed in IMCE cells but not YAMC cells. Under serum-free
      conditions, adiponectin (1 mug/ml) inhibited leptin-induced autocrine IL-6
      production, soluble IL-6 receptor shedding, trans-IL-6 signaling and subsequent
      STAT3 phosphorylation in IMCE cells. Adiponectin inhibited leptin-induced cell
      proliferation in the IMCE cells and this inhibition was associated with I kappa B
      alpha phosphorylation, I kappa B-alpha degradation and decreased NF-kappaB p65
      DNA activation and binding. These data indicate that adiponectin acts on
      preneoplastic colon epithelial cells to regulate cell growth via 2 distinct
      pathways inhibiting leptin-induced NF-kappaB-dependent autocrine IL-6 production
      and trans-IL-6 signaling. We hypothesize that adiponectin may be an important
      regulator of colon epithelial cell homeostasis by linking the observed reduced
      risk for cancer in populations with high serum adiponectin concentrations to
      specific mechanisms of cell number homeostasis in a model of preneoplastic colon
      epithelial cells. These data may have broad implications for diet and lifestyle
      strategies for the prevention and treatment of obesity-associated cancers.

PMID- 18338751
TI  - Combination of oncolytic adenovirotherapy and Bax gene therapy in human cancer
      xenografted models. Potential merits and hurdles for combination therapy.
AB  - Cancer gene therapy and oncolytic virotherapy have been studied extensively.
      However, their clinical application is hampered by their weak anticancer
      activity. We previously constructed a replicating adenovirus (OBP-301,
      Telomelysin), in which the human telomerase reverse transcriptase (hTERT)
      promoter drives expression of the adenoviral E1 genes, and causes selective lysis
      of human cancer cells. We hypothesized that combination adenoviral therapy
      containing OBP-301 and a nonreplicating adenovirus expressing the proapoptotic
      Bax gene could overcome the weakness and augment the anticancer efficacy of each
      modality. Combination treatment resulted in marked Bax protein expression and
      enhanced efficacy in in vitro cell viability assay, when compared with either
      single treatment. However, combination treatment was not as effective in
      suppressing both subcutaneous and pleural disseminated tumors compared with OBP
      301 treatment alone. Further investigation revealed that combination treatment
      resulted in suppressed E1A protein expression associated with reduced viral
      replication. Our results suggest that Bax gene therapy in combination with
      oncolytic adenovirotherapy potentially augments their antitumor activity, but
      further improvements may be required to maximize the combinatorial effect in
      vivo, for the Bax gene expression to avoid interference with production of the
      oncolytic virus.

PMID- 18338752
TI  - Cervical cancer screening program integrating Pap smear and HPV DNA testing: a
      population-based study.
AB  - We conducted a population-based cohort study to evaluate the complementary value
      of HPV testing to Papanicolaou (Pap) smear and the prevalence and genotype
      distribution of HPV in Taiwan. In this report, we described the design of the
      whole study and analyzed the cross-sectional results. Female residents (age >or=
      30 years) of Taoyuan, Taiwan were invited. After signing informed consent, every
      participant had a Pap smear and a HPV testing. Patients with Pap >or= atypical
      squamous cell of undetermined significance (Group I) or those with HPV-positive
      but normal cytology (Group II) were referred for a colposcopic examination. A
      total of 10,014 women were eligible. The overall HPV prevalence was 10.8% (95%
      confidence interval 10.5%-11.4%) in the study population. A total of 37 types of
      HPV were identified and the leading three were HPV-52, -18 and -58. There was a
      significant positive correlation of HPV prevalence with older age, postmenopausal
      status, current-user of oral contraceptives and never-user of hormone replacement
      therapy. Past users of oral contraceptives and never users of Pap were associated
      with higher risk of abnormal Pap, while age 40-49 strata had lower risk. Fifty
      nine cases of cervical intraepithelial neoplasia (CIN) 2 from Group I and
      additional 11 from Group II were identified. The improvement of sensitivity with
      additional HPV testing was 15.3%. Besides, no specific subgroup was found to most
      benefit from the combined strategy. The value of adding HPV test to conventional
      Pap smear has to be evaluated after longer-term follow-up of this population
      based cohort.

PMID- 18338753
TI  - alpha-Galactosylceramide-loaded, antigen-expressing B cells prime a wide spectrum
      of antitumor immunity.
AB  - Most of the current tumor vaccines successfully elicit strong protection against
      tumor but offer little therapeutic effect against existing tumors, highlighting
      the need for a more effective vaccine strategy. Vaccination with tumor antigen
      presenting cells can induce antitumor immune responses. We have previously shown
      that NKT-licensed B cells prime cytotoxic T lymphocytes (CTLs) with epitope
      peptide and generate prophylactic/therapeutic antitumor effects. To extend our B
      cell vaccine approach to the whole antigen, and to overcome the MHC restriction,
      we used a nonreplicating adenovirus to transduce B cells with antigenic gene.
      Primary B cells transduced with an adenovirus-encoding truncated Her-2/neu (AdHM)
      efficiently expressed Her-2/neu. Compared with the moderate antitumor activity
      induced by vaccination with adenovirus-transduced B cells (B/AdHM), vaccination
      with alpha-galactosylceramide-loaded B/AdHM (B/AdHM/alpha GalCer) induced
      significantly stronger antitumor immunity, especially in the tumor-bearing mice.
      The depletion study showed that CD4(+), CD8(+) and NK cells were all necessary
      for the therapeutic immunity. Confirming the results of the depletion study,
      B/AdHM/alpha GalCer vaccination induced cytotoxic NK cell responses but B/AdHM
      did not. Vaccination with B/AdHM/alpha GalCer generated Her-2/neu-specific
      antibodies more efficiently than B/AdHM immunization. More importantly,
      B/AdHM/alpha GalCer could prime Her-2/neu-specific cytotoxic T cells more
      efficiently and durably than B/AdHM. CD4(+) cells appeared to be necessary for
      the induction of antibody and CTL responses. Our results demonstrate that, with
      the help of NKT cells, antigen-transduced B cells efficiently induce innate
      immunity as well as a wide range of adaptive immunity against the tumor,
      suggesting that they could be used to develop a novel cellular vaccine.

PMID- 18338754
TI  - Intake of flavonoids and risk of cancer in Finnish men: The Kuopio Ischaemic
      Heart Disease Risk Factor Study.
AB  - Limited amount of evidence suggests that high intake of flavonoids could be
      associated with decreased risk of lung and colorectal cancer, but more studies
      are needed. In this prospective cohort study, we assessed the relation between
      the intakes of 26 flavonoids from 5 subclasses; flavonols, flavones, flavanones,
      flavan-3-ols and anthocyanidins, and the risk of lung, prostate and colorectal
      cancer. The study population consisted of 2,590 middle-aged eastern Finnish men
      of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor
      (KIHD) Study. The mean intake of flavonoids was 131.0 +/- 214.7 mg/day. During
      the mean follow-up time of 16.2 years, 62 lung, 138 prostate, and 55 colorectal
      cancers occurred. All lung cancer cases occurred among either current smokers (n
      = 50) or previous smokers (n = 12). After adjustment for age, examination years,
      body mass index, smoking status, pack-years of smoking, physical activity and
      intakes of alcohol, total fat, saturated fat, fiber, vitamin C and E, relative
      risk (RR) for lung cancer was 0.27 (95% CI: 0.11-0.66) for the highest quarter of
      total flavonoid intake as compared with the lowest quarter. Out of 5 flavonoid
      subclasses, flavonols and flavan-3-ols were associated with lung cancer, for the
      highest quarter of intake the RR were 0.29 (95% CI: 0.11-0.78) and 0.24 (95% CI:
      0.09-0.64), respectively. No association between flavonoid intake and risk of
      prostate or colorectal cancer were found. We conclude that high intake of
      flavonoids is associated with decreased risk of lung cancer in middle-aged
      Finnish smoking men.

PMID- 18338755
TI  - Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor
      nilotinib and Abl/Lyn inhibitor INNO-406 in newly established K562 variants with
      BCR-ABL gene amplification.
AB  - Because imatinib (IM) resistance in chronic myeloid leukemia is primarily caused
      by the re-establishment of Abl kinase, new inhibitors may be efficacious. We
      evaluated 3 new agents against 2 new K562 variants, IM-R1 and IM-R2 cells, which
      were developed having 7- and 27-fold greater IM resistance, respectively, than
      the parental K562 cells. Both variants possessed BCR-ABL gene amplification along
      with elevated levels of its transcript and protein. Greater BCR-ABL gene
      amplification was observed in IM-R2 cells than in IM-R1 cells, which was
      consistent with the higher mRNA and protein levels of Bcr-Abl, and ultimately
      correlated with the greater IM resistance in IM-R2 cells. No mutation in the Abl
      kinase domain was detected in either variant. Despite the absence of Lyn
      overexpression, the Src kinase inhibitor CGP76030 showed positive cooperability
      with IM in inhibiting cell growth of not only K562 cells but also these 2
      variants. This might be because of the augmented inhibition of Erk1/2
      phosphorylation. The new Abl kinase inhibitor nilotinib was 10-fold more potent
      than IM in inhibiting the growth of K562 cells. Nilotinib inhibited the growth of
      IM-R1 and IM-R2 cells as potently as K562 cells. The combination of nilotinib
      with CGP76030 showed little additivity, because the potency of nilotinib masked
      the efficacy of CGP76030. The new dual Abl/Lyn inhibitor INNO-406 (formerly NS
      187) was slightly more potent than nilotinib in inhibiting the growth of all 3
      cell lines. Because BCR-ABL gene amplification occurs in blast crisis, these
      inhibitors might overcome IM resistance in such patients' leukemia.

PMID- 18338756
TI  - VEGF-D promotes tumor growth and lymphatic spread in a mouse model of
      hepatocellular carcinoma.
AB  - Lymphatic spread is an important clinical determinant for the prognosis of
      hepatocellular carcinoma (HCC), but little is known about the control of
      lymphangiogenesis in HCC. We addressed expression and biological role of the pro
      (lymph), angiogenic protein VEGF-D in this tumor entity. Using
      immunohistochemistry and in situ hybridization on specimens of HCC, cirrhotic and
      normal liver we found abundant expression of VEGF-D exclusively in the tumor
      cells. The cognate receptor VEGFR-3 was detected on blood and lymphatic vessels.
      By clinicopathological analysis VEGF-D expression was correlated with pT-stage of
      the primary, lymph node metastasis and lymphangiosis carcinomatosa. Three out of
      4 human HCC cell lines expressed and secreted VEGF-D. To approach its biological
      function, VEGF-D deficient SKHep-1 cells were stably transfected with VEGF-D cDNA
      and effects on tumor progression were determined in vivo. Compared to mock
      transfected controls, subcutaneous tumors derived from VEGF-D expressing cells
      were larger and more frequently metastasized to regional lymph nodes. VEGF-D
      expressing tumors exhibited increased microvessel density and increased abundance
      of peri- and intratumoral lymphatics, as assessed by immunostaining for CD31 and
      for LYVE-1 and/or podoplanin, respectively. Furthermore, coexpression of the
      soluble extracellular VEGFR-3 domain blocked VEGF-D-induced tumor growth and
      lymphatic spread via reduction of angiogenesis and lymphangiogenesis. In the
      orthotopic approach, VEGF-D expression resulted in an increased rate of intra-
      and extrahepatic as well as lymph node metastasis. In conclusion, our study
      suggests that expression of VEGF-D is involved in growth and lymphatic spread of
      HCC. Therefore, VEGF-D might represent a therapeutic target in HCC.

PMID- 18338757
TI  - Neoadjuvant therapy for soft tissue sarcomas: does it make a difference?

PMID- 18338758
TI  - Changes in causes of death over time after treatment for invasive aspergillosis.
AB  - BACKGROUND: Assessment of response to invasive aspergillosis (IA) therapy has
      been challenging in treatment trials. METHODS: The causes of death over 12 weeks
      were categorized prospectively by a blinded data review committee using a priori
      defined criteria in participants in a randomized comparative trial of
      voriconazole versus amphotericin B as first-line therapy of proven or probable
      IA. RESULTS: Death occurred in 98 of 277 patients during the 12-week course of
      study. Seventy-three of the 98 deaths (74%) occurred in the first 6 weeks; 25
      deaths occurred during the second 6 weeks. Of the 73 deaths during the first 6
      weeks, 50 (68%) were judged to be attributable to IA. Of the 25 deaths during the
      second 6 weeks, only 6 (24%) were judged to be attributable to IA. Fifty of the
      56 deaths (89%) attributable to IA occurred during the first 6 weeks.
      CONCLUSIONS: These data suggest that most deaths due to IA occur during the first
      6 weeks after the start of therapy and 6 weeks may be a better interval to judge
      the effectiveness of antifungal therapy because most deaths after 6 weeks are due
      to causes related to the underlying disease and its treatment rather than due to
      IA. Attributable mortality when assessed using a priori definitions and conducted
      in a blinded manner by a central data review committee can be useful in the
      assessment of IA therapy.

PMID- 18338759
TI  - Efficacy of stereotactic radiosurgery as a salvage treatment for recurrent
      malignant gliomas.
AB  - BACKGROUND: The objective of this prospective cohort study was to determine the
      efficacy of stereotactic radiosurgery (SRS) as a salvage treatment in patients
      with recurrent malignant gliomas. METHODS: Between January 2000 and December
      2006, 114 consecutive patients were treated with SRS as a salvage treatment for
      recurrent malignant gliomas at a single institution. Clinical outcome and its
      prognostic factors were analyzed and compared with the historical control group
      who were treated at the same institution between 1995 and 1999. RESULTS: The
      median overall survival from the time of diagnosis was 37.5 months (95%
      confidence interval [95% CI], 11.7-63.2 months) for patients with grade 3 gliomas
      (according to World Health Organization criteria) and was 23 months (95% CI, 16.2
      29.3 months) for patients with glioblastomas. The median progression-free
      survival after SRS was 8.6 months (95% CI, 1.1-16.2 months) for patients with
      grade 3 gliomas and 4.6 months for patients with glioblastomas (95% CI, 4.0-5.2
      months). With regard to treatment-related complications, radiation-induced
      necrosis was observed in 22 of 114 patients (24.4%). Compared with this historic
      control group, SRS significantly prolonged survival as a salvage treatment in
      patients with recurrent glioblastomas (23 months vs 12 months; P < .0001), but it
      was not found to provide a significant surgical benefit in patients with
      recurrent grade 3 gliomas (37.5 months vs 26 months; P = .789). On univariate
      analysis of prognostic factors, tumor volume (<10 mL) and low histologic grade
      were found to significantly influence better survival (P = .009 and P = .041,
      respectively). CONCLUSIONS: SRS is a safe and effective modality in selected
      patients with recurrent small-sized glioblastomas. However, the efficacy of SRS
      for recurrent grade 3 gliomas needs to be further evaluated in well-designed
      clinical studies.

PMID- 18338760
TI  - Re: Neoadjuvant therapy followed by prostatectomy for clinically localized
      prostate cancer.

PMID- 18338761
TI  - Quantitative data analysis methods for bead-based DNA hybridization assays using
      generic flow cytometry platforms.
AB  - Bead-based assays are in demand for rapid genomic and proteomic assays for both
      research and clinical purposes. Standard quantitative procedures addressing raw
      data quality and analysis are required to ensure the data are consistent and
      reproducible across laboratories independent of flow platform. Quantitative
      procedures have been introduced spanning raw histogram analysis through to
      absolute target quantitation. These included models developed to estimate the
      absolute number of sample molecules bound per bead (Langmuir isotherm), relative
      quantitative comparisons (two-sided t-tests), and statistical analyses
      investigating the quality of raw fluorescence data. The absolute target
      quantitation method revealed a concentration range (below probe saturation) of
      Cy5-labeled synthetic cytokeratin 19 (K19) RNA of c.a. 1 x 10(4) to 500 x 10(4)
      molecules/bead, with a binding constant of c.a. 1.6 nM. Raw hybridization
      frequency histograms were observed to be highly reproducible across 10 triplex
      assay replicates and only three assay replicates were required to distinguish
      overlapping peaks representing small sequence mismatches. This study provides a
      quantitative scheme for determining the absolute target concentration in nucleic
      acid hybridization reactions and the equilibrium binding constants for individual
      probe/target pairs. It is envisaged that such studies will form the basis of
      standard analytical procedures for bead-based cytometry assays to ensure
      reproducibility in inter- and intra-platform comparisons of data between
      laboratories.

PMID- 18338762
TI  - Spontaneous multiperforation in lymphomatous colitis masquerading as Crohn's
      disease: 2 cases.

PMID- 18338763
TI  - Association of IL23R, TNFRSF1A, and HLA-DRB1*0103 allele variants with
      inflammatory bowel disease phenotypes in the Finnish population.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC), 2 major forms of
      inflammatory bowel disease (IBD), are complex disorders with significant genetic
      predisposition. The first CD-associated gene, CARD15/NOD2, was recently
      identified and since then several reports on novel IBD candidate genes have
      emerged. We investigated disease phenotype association to genetic variations in
      IL23R, ATG16L1, DLG5, ABCB1/MDR1, TLR4, TNFRSF1A, chromosome 5 risk haplotype
      including SLC22A4 and SLC22A5, and HLA-DRB1*0103 allele among Finnish IBD
      patients. METHODS: A total of 699 IBD patients were genotyped for disease
      associated variants by polymerase chain reaction (PCR) and restriction enzyme
      digestion or Sequenom iPLEX method. RESULTS: Five markers spanning the IL23R gene
      were associated with CD. The SNP (single nucleotide polymorphism) rs2201841 gave
      the strongest association (P = 0.002). The rare HLA-DRB1*0103 allele was found to
      associate with UC (P = 0.008), and the TNFRSF1A A36G variant was associated with
      familial UC (P = 0.007). Upon phenotypic analysis we detected association between
      familial UC and rare TNFRSF1A alleles 36G and IVS6+10G (P = 0.001 and P = 0.042,
      respectively). In addition, IL23R markers were associated with stricturing CD (P
      = 0.010-0.017), and ileocolonic CD was more prevalent in the carriers of the same
      2 TNFRSF1A variants (P = 0.021 and P = 0.028, respectively). Less significant
      genotype-phenotype associations were observed for the TLR4 and HLA variants.
      CONCLUSIONS: We were able to replicate the association of the IL23R variants with
      CD as well as HLA-DRB1*0103 with UC; confirmation of TNFRSF1A association with UC
      needs additional studies. Our findings also suggest that polymorphisms at IL23R
      and TNFRSF1A, and possibly HLA and TLR4, loci may account for phenotypic
      variation in IBD.

PMID- 18338764
TI  - Capsaicin modulates pulmonary antioxidant defense system during benzo(a)pyrene
      induced lung cancer in Swiss albino mice.
AB  - The effect of a pungent ingredient of red pepper, capsaicin, on oxidative stress
      induced changes in the antioxidant defense system by benzo(a)pyrene in the lungs
      of mice was studied. Oral gavage administration of benzo(a)pyrene (50 mg/kg body
      weight) to mice led to a marked increase in oxidative stress indicated by
      alterations in pulmonary lipid peroxidation, enzymic antioxidants (superoxide
      dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S
      transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants
      (reduced glutathione, vitamin C, vitamin E and vitamin A). Pre-co-treatment with
      capsaicin (10 mg/kg body weight i.p.) restored cellular normalcy, highlighting
      the antioxidant potential of capsaicin in mitigating the oxidative stress
      mediated damage produced during benzo(a)pyrene-induced lung cancer.

PMID- 18338765
TI  - The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from
      Pterospartum tridentatum, on oral glucose tolerance in rats.
AB  - The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose
      levels of normal Wistar rats was investigated in a situation of oral glucose
      challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the
      first 30 min after glucose challenge but then the blood glucose levels rose above
      those of the control group, indicating the presence of compounds with different
      effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons
      were identified in the extract by HPLC-ESI-MS(n), four of them being identified
      for the first time in this species. The isoflavone sissotrin and the flavonol
      derivative, isoquercitrin, were selected for the oral glucose tolerance test.
      Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by
      delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium
      dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast,
      sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In
      conclusion, these preliminary results indicate that the effect of the extract on
      blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally,
      as far as is known, these are the first in vivo results on the acute
      antihyperglycaemic potential of isoquercitrin.

PMID- 18338766
TI  - Sexual dysfunction in schizophrenia: focus on recent evidence.
AB  - BACKGROUND: Antipsychotic medications are known to be commonly associated with
      sexual dysfunction. Sexual dysfunction is estimated to affect 30-80% of patients
      with schizophrenia and is a major cause of poor quality of life. However, few
      comparative studies on the sexual dysfunction effects associated with
      antipsychotic medication have been published and the effects of the newer
      atypical antipsychotics have been largely unexamined. OBJECTIVE: This review aims
      to examine the latest evidence regarding the sexual function effects of different
      antipsychotic medications, particularly the newer prolactin-sparing drugs,
      quetiapine and aripiprazole, in patients with schizophrenia and schizoaffective
      psychosis. METHODS: A literature search was conducted within PubMed/MEDLINE using
      the terms risperidone, haloperidol, clozapine, olanzapine, ziprasidone,
      quetiapine, aripiprazole; sexual dysfunction; schizophrenia. The results were
      limited to studies published since 2002. RESULTS: Recently published studies show
      that the relative impact of antipsychotics on sexual dysfunction can be
      summarised as risperidone > typical antipsychotics (haloperidol) > olanzapine >
      quetiapine > aripiprazole. CONCLUSIONS: The availability of prolactin-sparing
      antipsychotics should enable psychiatrists to consider and manage proactively the
      sexual function consequences of pharmacological intervention, thereby improving
      sexual side effects, which may lead to improved treatment adherence and
      psychiatric outcome in patients with schizophrenia.

PMID- 18338767
TI  - Reliability of the assessment of preventable adverse drug events in daily
      clinical practice.
AB  - PURPOSE: To determine the reliability of the assessment of preventable adverse
      drug events (ADEs) in daily practice and to explore the impact of the assessors'
      professional background and the case characteristics on reliability. METHODS: We
      used a combination of the simplified Yale algorithm and the National Coordinating
      Council for Medication Error Reporting and Prevention (NCC MERP) scheme to assess
      on the one hand the causal relationship between medication errors (MEs) and
      adverse events in hospitalised patients and on the other hand the severity of the
      clinical consequence of MEs. Five pharmacists and five physicians applied this
      algorithm to 30 potential MEs. After individual assessment, the pharmacists
      reached consensus and so did the physicians. Outcome was both MEs' severity
      (ordinal scale, NCC MERP categories A-I) and the occurrence of preventable harm
      (binary outcome, NCC MERP categories A-D vs. E-I). Kappa statistics was used to
      assess agreement. RESULTS: The overall agreement on MEs' severity was fair for
      the pharmacists (kappa = 0.34) as well as for the physicians (kappa = 0.25).
      Overall agreement for the 10 raters was fair (kappa = 0.25) as well as the
      agreement between both consensus outcomes (kappa = 0.30). Agreement on the
      occurrence of preventable harm was higher, ranging from kappa = 0.36 for the
      physicians through kappa = 0.49 for the pharmacists. Overall agreement for the 10
      raters was fair (kappa = 0.36). The agreement between both consensus outcomes was
      moderate (kappa = 0.47). None of the included case characteristics had a
      significant impact on agreement. CONCLUSIONS: Individual assessment of
      preventable ADEs in real patients is difficult, possibly because of the difficult
      assessment of contextual information. Best approach seems to be a consensus
      method including both pharmacists and physicians.

PMID- 18338768
TI  - Anthraquinones from Polygonum cuspidatum as tyrosinase inhibitors for dermal use.
AB  - Four anthraquinones, physcion (1), emodin (2), citreorosein (3) and
      anthraglycoside B (6), and two stilbenes, resveratrol (4), and piceid (5), were
      isolated previously from the root of Polygonum cuspidatum. These bioactive
      compounds were examined for their antityrosinase potency. No antityrosinase
      activity was detected with treatment using stilbenes. On the other hand, the
      anthraquinones showed moderate to strong inhibition of tyrosinase. Physcion
      exhibited the most potent tyrosinase inhibition among the four anthraquinones
      examined, which was comparable to kojic acid. The ability of anthraquinones to
      permeate the skin was also examined. Based on the same thermodynamic activity,
      physcion showed a higher permeation compared with emodin (48-fold), suggesting it
      as a potent candidate for dermal use. As naturally occurring tyrosinase
      inhibitors, anthraquinones from P. cuspidatum may be useful as skin-whitening
      agents to inhibit tyrosinase for dermal use.

PMID- 18338769
TI  - Inhibition of cholinesterase and amyloid-beta aggregation by resveratrol
      oligomers from Vitis amurensis.
AB  - In the course of screening for acetylcholinesterase and butyrylcholinesterase
      inhibitors from natural products by an in vitro Ellman method, the extract of the
      roots of Vitis amurensis Rupr. (Vitaceae) showed significant cholinesterase
      inhibitory activity. Employing a bioassay-linked HPLC method, followed by a semi
      preparative HPLC method, two compounds of interest were isolated and
      characterized as vitisin A and heyneanol A. They inhibited effectively both
      acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner and
      exhibited higher activity against butyrylcholinesterase compared with that of
      galantamine, a positive control. Furthermore, the aggregation of beta-amyloid was
      evaluated in vitro based on a thioflavine T fluorescence assay to expand their
      activity profile, with the result that both compounds showed the ability to block
      beta-amyloid aggregation.

PMID- 18338770
TI  - Quercus infectoria: a candidate for the control of methicillin-resistant
      Staphylococcus aureus infections.
AB  - Acetone, ethyl acetate, 95% ethanol and aqueous extracts of Quercus infectoria
      (Q. infectoria) demonstrated significant antibacterial activities against all
      strains of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin
      susceptible Staphylococcus aureus (MSSA). Inhibition zones were in the range
      11.75-16.82 mm. Both MRSA and MSSA strains exhibited minimum inhibitory
      concentration (MIC) and minimum bactericidal concentration (MBC) values at 0.13
      and 0.13-1.00 mg/mL, respectively. At 2 MIC, the growth of two representative
      MRSA strains was continually inhibited for at least 20 h. Surviving MRSA cells
      were not detected within 12-14 h after treatment with the extract at 4 MIC
      concentration. Staphylococcus aureus ATCC 25923 demonstrated similar results.

PMID- 18338771
TI  - Antimycobacterial activity of Juglans regia, Juglans mollis, Carya illinoensis
      and Bocconia frutescens.
AB  - Mycobacterium tuberculosis is a serious worldwide health threat, killing almost 2
      million people per year. Alternative antimycobacterial drugs are urgently needed;
      studies have shown that medicinal plants traditionally used to treat respiratory
      diseases are a potential source of compounds to treat tuberculosis. This paper
      studied the antimycobacterial activity of 28 extracts from four different plant
      species that have been used in traditional Mexican medicine to treat
      tuberculosis. Bark and leaf crude extracts of Juglans regia L., Juglans mollis
      Engelm., Carya illinoensis (Wangenh) K. Koch and Bocconia frutescens showed in
      vitro anti-M. tuberculosis activity. Hexane bark extracts from C. illinoensis, J.
      mollis and J. regia were the most active with a minimal inhibitory concentration
      (MIC) of 31, 50 and 100 microg/mL, respectively. Ethanol bark extracts from C.
      illinoensis and J. mollis showed activity at 100 and 125 microg/mL, respectively.
      Leaf extracts had the lowest activity. Methanol and hexane leaves extracts from
      B. frutescens had a MIC of 125 microg/mL. None of the aqueous extracts showed
      antimycobacterial activity.

PMID- 18338772
TI  - How important is mesalamine in the maintenance of steroid-refractory colitis?

PMID- 18338773
TI  - Postoperative recurrence of Crohn's disease and videocapsule endoscopy: it is
      necessary to leave no stone unturned.

PMID- 18338774
TI  - Disease perceptions among people with Crohn's disease.
AB  - BACKGROUND: The relationship between Crohn's disease (CD) patients' perceptions
      of overall disease course to severity measures based on current symptomatology
      has not been fully explored. We sought to characterize CD patient perceptions of
      both overall disease course and current symptomatology based on an objective
      symptom scale and to explore the relationship between perceptions and current
      symptoms. METHODS: Patients were screened by telephone and those who met
      inclusion criteria were invited to complete a full, self-administered online
      survey. RESULTS: Respondents (n = 1205) were predominantly female (66%) and
      Caucasian (92%); the median age was 44 years. Self-perceived overall disease
      course was described as "mild" in 16%, "moderate" in 50%, and "severe" in 34%;
      these correlated poorly with objective measures of current symptomatology.
      Perceived current symptomatology was "mild" in 61%, "moderate" in 29%, and
      "severe" in 10%. Patients perceived their overall disease course as more severe
      than that reflected by current symptomatology. Among 61% who had "mild" disease
      based on 30-day symptoms, only 16% rated themselves as having a mild disease
      course overall. Similar results among those in the "moderate" and "severe"
      overall disease categories indicated poor congruence between perceived overall
      disease course and measures of current disease symptomatology. CONCLUSIONS:
      Perceptions of overall disease severity may not correlate with disease activity
      measures based on current symptomatology. Patients rely on physicians to guide
      treatment choices; thus, a more complete appreciation of patients' disease
      perceptions that includes both overall disease course and current symptomatology
      may help inform treatment decisions, and could potentially improve patient care.

PMID- 18338775
TI  - Geographic distribution and ecological studies of inflammatory bowel disease in
      southeastern Norway in 1990-1993.
AB  - BACKGROUND: The purpose was to study the spatial distribution of cases of
      inflammatory bowel disease (IBD) and characterize municipalities with high
      incidences in a search for environmental risk factors. METHODS: Spatial
      clustering of patients diagnosed with IBD during 1990-1993 were studied in 4
      counties in southeastern Norway, and an ecological analysis was conducted to
      study the relationship between risk of IBD in the municipalities and their
      characteristics such as population, health care, urban/rural change, and
      socioeconomic change. RESULTS: One cluster consisting of 4 municipalities was
      identified for IBD in Ostfold county (P = 0.011). The ecological analysis showed
      that the incidence rate of IBD was 33% (95% confidence interval [CI]: 2%-75%)
      higher in municipalities with the highest level of education compared to the
      lowest level of education and 35% (2%-78%) higher in urban than rural
      municipalities. The incidence rate was 11% (1%-20%) lower in municipalities with
      a high urban/rural change compared to municipalities with low urban/rural change.
      Individuals living in high-risk municipalities were 3 times (1.57-5.45) more
      likely to have a first-degree family member with IBD than individuals living in
      normal-risk municipalities. CONCLUSIONS: The geographic distribution of cases
      with IBD is not uniformly distributed and is related to urbanization, level of
      education, and moving pattern. Geographic distribution may be explained by either
      changes in environment-host relationships or neurobiological mechanisms due to
      stress and economic frustration. These factors and genetic predisposition might
      also explain increased familial clustering. Spatial clustering was significant
      neither for Crohn's disease CD nor ulcerative colitis (UC) but showed a stronger
      tendency within the CD group.

PMID- 18338776
TI  - Contribution of TNFSF15 gene variants to Crohn's disease susceptibility confirmed
      in UK population.
AB  - BACKGROUND: Identification of Crohn's disease (CD)-associated genetic variants is
      key to understanding pathogenic pathways underlying disease susceptibility.
      Recent reports of an association between TNFSF15 variants and CD have been
      modestly replicated in European populations, suggesting heterogeneity at this
      locus with stronger CD association in Japanese than European populations.
      METHODS: We investigated the association between variants in TNFSF15 and CD in
      756 CD patients and 636 controls. Disease subphenotype associations were also
      investigated. RESULTS: TNFSF15 single nucleotide polymorphism (SNP) variants were
      associated with CD in our panel with peak odds ratio (OR) 1.2 (95% confidence
      interval [CI] 1.01-1.41) P = 0.033. The presence of a risk haplotype was
      replicated for the first time in a European population (frequency 67% in cases
      and 61% in controls) OR = 1.44 (95% CI 1.23-1.68) P = 0.00012. This result
      mirrors the UK panel in the index study (Yamazaki et al [2005] Hum Mol Genet
      14:3499-3506) but is less significant than that reported in Japanese populations.
      There was no evidence of association with any individual CD subphenotype.
      CONCLUSIONS: Variants in TNFSF15 contribute to overall CD susceptibility in
      European populations, although to a lesser extent than that seen in the Japanese.
      Further studies to define the precise disease-causing variants as well as
      targeted functional studies are now required in human CD as TNFSF15 is a
      potential target for biological therapies.

PMID- 18338777
TI  - Flow cytometry sets eyes on the iron LIP.

PMID- 18338778
TI  - A high-throughput system for segmenting nuclei using multiscale techniques.
AB  - Automatic segmentation of cell nuclei is critical in several high-throughput
      cytometry applications whereas manual segmentation is laborious and
      irreproducible. One such emerging application is measuring the spatial
      organization (radial and relative distances) of fluorescence in situ
      hybridization (FISH) DNA sequences, where recent investigations strongly suggest
      a correlation between nonrandom arrangement of genes to carcinogenesis. Current
      automatic segmentation methods have varying performance in the presence of
      nonuniform illumination and clustering, and boundary accuracy is seldom assessed,
      which makes them suboptimal for this application. The authors propose a modular
      and model-based algorithm for extracting individual nuclei. It uses multiscale
      edge reconstruction for contrast stretching and edge enhancement as well as a
      multiscale entropy-based thresholding for handling nonuniform intensity
      variations. Nuclei are initially oversegmented and then merged based on area
      followed by automatic multistage classification into single nuclei and clustered
      nuclei. Estimation of input parameters and training of the classifiers is
      automatic. The algorithm was tested on 4,181 lymphoblast nuclei with varying
      degree of background nonuniformity and clustering. It extracted 3,515 individual
      nuclei and identified single nuclei and individual nuclei in clusters with 99.8
      +/- 0.3% and 95.5 +/- 5.1% accuracy, respectively. Segmented boundaries of the
      individual nuclei were accurate when compared with manual segmentation with an
      average RMS deviation of 0.26 microm (approximately 2 pixels). The proposed
      segmentation method is efficient, robust, and accurate for segmenting individual
      nuclei from fluorescence images containing clustered and isolated nuclei. The
      algorithm allows complete automation and facilitates reproducible and unbiased
      spatial analysis of DNA sequences.

PMID- 18338779
TI  - Comprehensive pouch clinic concept for follow-up of patients after ileal pouch
      anal anastomosis: report of 3 years' experience in a tertiary referral center.
AB  - BACKGROUND: We designed and evaluated a novel concept in enhancing postoperative
      care of patients following restorative proctocolectomy (RPC) for ulcerative
      colitis (UC) and determined the risk factors, incidence, and nature of RPC
      associated complications in this population. METHODS: The study cohort consisted
      of consecutive UC patients post-RPC attending a comprehensive pouch clinic run by
      a gastroenterologist and a colorectal surgeon in a tertiary care medical center
      (from January 2003 to December 2005). Data were collected on their medical
      history, physical examination, laboratory tests, pouch endoscopy and biopsies,
      and anonymous in-house patient satisfaction questionnaires mailed to the first 90
      patients. Assessment was also done on data regarding risk factors, incidence, and
      nature of RPC-associated complications. RESULTS: A total of 120 UC patients with
      a functioning pouch visited the clinic: mean age 37 years, range 13-75; 57 males;
      mean disease duration 11 years; mean follow-up 65 months. Of the 55 patients who
      responded to the questionnaire, 48 (87%) felt that the comprehensive clinic
      significantly improved the quality of their care. The major complications were
      pouchitis (52%), extraintestinal manifestations, pouch-related fistula, and
      mechanical dysfunction. The risk factors for the development of pouchitis were
      time since surgery, >1-stage surgery, and reason for surgery (acute
      exacerbation/intractable disease more than dysplasia/cancer); the latter was the
      only independent risk factor. CONCLUSIONS: The pouch clinic concept significantly
      enhanced patient satisfaction. The most common RPC-associated complication was
      pouchitis. Risk factors for developing pouchitis were duration since operation,
      >1-stage operation, and indication for surgery.

PMID- 18338780
TI  - Crohn's disease-associated Escherichia coli LF82 aggravates colitis in injured
      mouse colon via signaling by flagellin.
AB  - BACKGROUND: Ileal lesions in Crohn's disease patients are colonized by pathogenic
      adherent-invasive Escherichia coli (AIEC) that harbor various virulence factors
      involved in adhesion to and invasion of intestinal epithelial cultured cells. We
      investigated in a mouse model of colonic inflammation the behavior of virulent
      AIEC reference bacteria LF82 compared to that of nonflagellated LF82 mutants.
      METHODS: BALBc/J mice with intact or dextran sulfate sodium (DSS)-injured colon
      were orally challenged daily with 10(8) bacteria. The severity of colitis was
      assessed by determining disease activity index, colonic histological score, and
      myeoloperoxidase activity. Flagellin receptor and cytokine expression was
      measured by reverse-transcriptase polymerase chain reaction (RT-PCR) in colonic
      tissue. RESULTS: In contrast to nonpathogenic E. coli, virulent LF82 bacteria
      exacerbated colitis in DSS-treated mice, substantially reducing survival rate,
      greatly lowering stool consistency, inducing marked weight loss and increased
      rectal bleeding, and significantly increasing erosive lesions and mucosal
      inflammation. Nonflagellated LF82 mutants behaved like nonpathogenic E. coli K
      12. Interestingly, oral infection with LF82 virulent bacteria, but not with a
      nonvirulent LF82 mutant, induced a 7.0-fold increase in the levels of TLR5 and a
      3.1-fold increase in those of ipaf mRNA, which encode respectively membrane and
      cytosolic receptors involved in the recognition of flagellin. Hence, a 5.6-fold
      increase in IL-1beta and a 5.3-fold increase in mRNA of IL-6 were observed in
      mice challenged with AIEC LF82 bacteria. CONCLUSIONS: Crohn's disease-associated
      virulent AIEC LF82 bacteria, via expression of flagella, are able to potentiate
      an inflammatory mucosal immune response involving increased expression of TLR5
      and IPAF flagellin receptors.

PMID- 18338781
TI  - Increased incidence of urinary matrix metalloproteinases as predictors of disease
      in pediatric patients with inflammatory bowel disease.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) are a family of metal-dependent
      enzymes responsible for the degradation and remodeling of extracellular matrix
      and basement membrane proteins that occurs during both normal physiologic
      activity and disease. It has been suggested that MMPs may also play a role in the
      pathogenesis of inflammatory bowel disease (IBD) by mediating mucosal breakdown
      in response to an enhanced inflammatory cascade. We previously demonstrated that
      elevated urinary MMP levels are independent predictors of disease status in
      cancer patients. Here we demonstrate that elevated urinary MMP levels may be
      biomarkers of disease activity in patients with IBD. METHODS: We analyzed 95
      urine samples prospectively collected from 55 children and young adults with
      known or suspected IBD who presented for evaluation to the Gastrointestinal
      Procedure Unit at Children's Hospital Boston. Urinary MMPs were analyzed in
      patients by zymography and compared to 40 age- and sex-matched controls. RESULTS:
      Urinary MMP levels were significantly elevated (P < 0.0001) in patients with IBD,
      as well as in each subgroup (Crohn's disease or ulcerative colitis), relative to
      controls. Multiple logistic regression revealed that urinary MMP-2 and MMP-9 NGAL
      levels were independent predictors of Crohn's disease and ulcerative colitis (P <
      0.0001). CONCLUSIONS: These data are the first to demonstrate that urinary MMPs
      may represent novel noninvasive biomarkers for use in the evaluation of patients
      with IBD.

PMID- 18338782
TI  - Hepatocyte nuclear factor 4alpha in the intestinal epithelial cells protects
      against inflammatory bowel disease.
AB  - BACKGROUND: Hepatocyte nuclear factor 4alpha (HNF4alpha; NR2A1) is an orphan
      member of the nuclear receptor superfamily expressed in liver and intestine.
      While HNF4alpha expression is critical for liver function, its role in the gut
      and in the pathogenesis of inflammatory bowel disease (IBD) is unknown. METHODS:
      Human intestinal biopsies from control and IBD patients were examined for
      expression of mRNAs encoding HNF4alpha and other nuclear receptors. An intestine
      specific HNF4alpha null mouse line (Hnf4alpha(DeltaIEpC)) was generated using an
      Hnf4alpha-floxed allele and villin-Cre transgene. These mice and their control
      floxed counterparts (Hnf4alpha(F/F)), were subjected to a dextran sulfate sodium
      (DSS)-induced IBD colitis protocol and their clinical symptoms and gene
      expression patterns determined. RESULTS: In human intestinal biopsies, HNF4alpha
      was significantly decreased in intestinal tissues from Crohn's disease and
      ulcerative colitis patients. HNF4alpha expression was also suppressed in the
      intestine of DSS-treated mice. In Hnf4alpha(DeltaIEpC) mice, disruption of
      HNF4alpha expression was observed in the epithelial cells throughout the
      intestine. In the DSS-induced colitis model Hnf4alpha(DeltaIEpC) mice showed
      markedly more severe changes in clinical symptoms and pathologies associated with
      IBD including loss of body weight, colon length, and histological morphology as
      compared with Hnf4alpha(F/F) mice. Furthermore, the Hnf4alpha(DeltaIEpC) mice
      demonstrate a significant alteration of mucin-associated genes and increased
      intestinal permeability, which may play an important role in the increased
      susceptibility to acute colitis following an inflammatory insult. CONCLUSIONS:
      While HNF4alpha does not have a major role in normal function of the intestine,
      it protects the gut against DSS-induced colitis.

PMID- 18338783
TI  - Hypoglycemic effect of a novel dialysed fenugreek seeds extract is sustainable
      and is mediated, in part, by the activation of hepatic enzymes.
AB  - A novel preparation of a dialysed aqueous extract of fenugreek seeds (FSE) that
      stimulates the insulin signalling pathway was reported previously (Vijayakumar et
      al., 2005). The present study was designed to investigate the long-term effects
      (multiple dose effect) of this FSE preparation on the blood glucose level and
      body weight, and a short-term effect (single dose effect) on serum insulin and
      hepatic enzymes, in experimentally induced diabetic conditions. The multiple dose
      effect of FSE on the glucose level and body weight was studied in alloxan (AXN)
      diabetic mice in comparison with the vehicle treated control diabetic mice.
      Intraperitoneal (i.p.) administration of FSE (15 mg/kg body weight (BW)) for 5
      consecutive days reduced hyperglycemia in AXN-diabetic mice on day 5 and this
      effect was further sustained for 10 days. The FSE-induced hypoglycemic effect was
      accompanied without any reduction in the body weight compared with the diabetic
      mice in which the body weight was reduced significantly. A single dose effect of
      FSE on hepatic glucokinase (GK) and hexokinase (HK) enzymes was studied in
      streptozotocin (STZ)-diabetic mice. Intraperitoneal administration of FSE (15
      mg/kg BW) by 90 min decreased the blood glucose levels significantly (p < 0.01)
      in STZ-diabetic mice and the effect was comparable to that achieved by insulin
      (1.5 U/kg BW) injection. This effect was associated with a significant
      enhancement in the liver GK and HK activities on a par with that of insulin. In
      normal glucose loaded mice, FSE improved the intraperitoneal glucose tolerance
      accompanied by a reduction in serum insulin concentration. These results are
      indicative of an extra-pancreatic mode of action of FSE. The present study
      concludes that this novel FSE preparation corrects metabolic alterations
      associated with diabetes by exhibiting insulin-like properties and has a
      potential for clinical applications.

PMID- 18338784
TI  - Inhibition of Ulmus davidiana Planch (Ulmaceae) on bone resorption mediated by
      processing of cathepsin K in cultured mouse osteoclasts.
AB  - Ulmus davidiana Planch (Ulmaceae) (UD) has long been known to be antiinflammatory
      in traditional Korean medicine. This experiment investigated the effects of UD on
      bone resorption using bone cell culture. Different concentrations of crude
      extract of UD were added to mouse bone cell culture. The mitochondrial activity
      of the bone cells after exposure of UD was determined by colorimetric 3-(4,5
      dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT). It was demonstrated
      that UD has potential effects on bone cell culture without cytotoxicity. The most
      effective concentration of UD in bone cells was 100 microg/mL. Cathepsin K (Cat
      K) is the major cysteine protease expressed in osteoclasts and is thought to play
      a key role in matrix degradation during bone resorption. When mouse long bone
      cells including osteoclasts and osteoblasts were treated with UD, UD prevented
      the osteoclast-mediated intracellular processing of Cat K, suggesting that UD may
      disrupt the intracellular transport of pro Cat K. Since secreted proenzymes have
      the potential to reenter the cell via the mannose-6-phosphate (M6P) receptor, to
      prevent this possibility, UD was tested in the absence or presence of M6P.
      Inhibition of Cat K processing by UD was observed in a dose-dependent manner.
      Furthermore, the addition of M6P resulted in enhanced potency of UD. UD dose
      dependently inhibited in vitro bone resorption with a potency similar to that
      observed for inhibition of Cat K processing.

PMID- 18338785
TI  - HDPE-Al2O3-HAp composites for biomedical applications: processing and
      characterizations.
AB  - The objective of this work is to demonstrate how the stiffness, hardness, as well
      as the biocompatibility property, of bioinert high-density polyethylene (HDPE)
      can be significantly improved by the combined addition of both bioinert and
      bioactive ceramic fillers. For this purpose, different volume fractions of
      hydroxyapatite and alumina, limited to a total of 40 vol %, have been
      incorporated in HDPE matrix. All the hybrid composites and monolithic HDPE were
      developed under optimized hot pressing condition (130 degrees C, 0.5 h, 92 MPa
      pressure). The results of the mechanical property characterization reveal that
      higher elastic modulus (6.2 GPa) and improved hardness (226.5 MPa) could be
      obtained in the developed HDPE-20 vol %-HAp-20 vol % Al(2)O(3) composite. Under
      the selected fretting conditions against various counterbody materials (steel,
      Al(2)O(3), and ZrO(2)), an extremely low COF of (0.07-0.11) and higher wear
      resistance (order of 10(-6) mm(3)/Nm) are obtained with the HDPE/20 vol % HAp/20
      vol % Al(2)O(3) composite in both air and simulated body fluid environment.
      Importantly, in-vitro cell culture study using L929 fibroblast cells confirms
      favorable cell adhesion properties in the developed hybrid composite.

PMID- 18338786
TI  - Freeze casting of porous hydroxyapatite scaffolds. II. Sintering, microstructure,
      and mechanical behavior.
AB  - In Part I, the influence of processing parameters on the general microstructure
      of freeze-cast hydroxyapatite (HA) constructs was explored. This work is an
      extension of Part I to investigate the effect of sintering conditions on the
      microstructure and mechanical behavior of freeze-cast HA. For constructs prepared
      from aqueous suspensions (5-20 vol % HA), sintering for 3 h at temperatures from
      1250 degrees C to 1375 degrees C produced a decrease in porosity of <5% but an
      increase in strength of nearly 50%. Constructs with a porosity of 52% had
      compressive strengths of 12 +/- 1 MPa and 5 +/- 1 MPa in the directions parallel
      and perpendicular to the freezing direction, respectively. The mechanical
      response showed high strain tolerance (5-10% at the maximum stress), high strain
      to failure (>20%), and high strain rate sensitivity. Manipulation of the freeze
      cast microstructure, achieved by additions of glycerol and 1,4-dioxane to the
      aqueous suspensions, produced changes in the magnitude of the mechanical
      response, but little change in the general nature of the response. The favorable
      mechanical behavior of the porous constructs, coupled with the ability to modify
      their microstructure, indicates the potential of the present freeze-casting route
      for the production of porous scaffolds for bone tissue engineering.

PMID- 18338787
TI  - Flexural strength, fatigue life, and stress-induced phase transformation study of
      Y-TZP dental ceramic.
AB  - OBJECTIVES: Yttria partially-stabilized zirconia polycrystalline (Y-TZP) has been
      the subject of extensive research because of its high strength and toughness. The
      aim of this study was to evaluate the biaxial flexural strength, fatigue life,
      and to investigate in more detail on single cycle specimens, the pressure-induced
      phase transformation of a Y-TZP dental ceramic using Raman microspectroscopy.
      MATERIALS AND METHODS: Thirty standardized discs (15 x 1.2 mm(2)) were used to
      examine the biaxial flexural strength (ISO 6872 standard) using a Dartec HC10
      Servohydraulic testing machine (Zwick Ltd., UK). The specimens were also
      submitted to Vickers hardness (on polished and as-received surfaces within the
      same specimen) and dynamic fatigue test. The initial bulk phases were examined
      via X-ray diffraction and the local phase transformations that occurred in the
      zirconia induced by the various Vickers indentation loads (20-50 kg) were
      examined via Raman microspectroscopy on single cycle specimens. The fracture
      surface after biaxial flexural testing was also examined via Raman spectroscopy.
      RESULTS: The Cercon specimens tested had flexural strength and Weibull modulus
      (m) of approximately 823.3 (+/-114.7) MPa and 8.3, respectively. As-received
      surfaces (1378.7 +/- 51.8 Hv) had slightly higher hardness value compared with
      polished surfaces (1354.33 +/- 50.9 Hv); however, two-way analysis of variance
      showed no significant difference in hardness values between polished and as
      received surfaces (P > 0.05). Additionally, the specimens survived to 5 x 10(5)
      cycles when using a load of 70% of the mean biaxial flexural strength or lower.
      Raman microspectroscopy showed transformation of tetragonal to cubic and
      monoclinic phases within the indentation area. The fraction of monoclinic phase
      showed only limited variation with load or distance from the center to
      indentation edge. The level of cubic phase, however, was greatest at the
      indentation center. Transformation to cubic phase was observed on the lower
      surfaces (tension side) of fractured specimens. It was also observed near the
      specimen center exposed upon fracture. In the latter region an increase in
      monoclinic phase was additionally observed. Further work will be carried out
      using Raman microspectroscopy to assess the effect of fatigue on phase
      transformations. CONCLUSION: The zirconia based ceramic has mechanical properties
      that may allow it to withstand the loading found in posterior areas.
      Transformation toughening was found when high loads impacted on the surface of
      zirconia. However it should be born in mind that this work was not carried out on
      veneered specimens, which exhibit different failure modes.

PMID- 18338788
TI  - Anger and assaultiveness of male forensic patients with developmental
      disabilities: links to volatile parents.
AB  - This study with 107 male forensic patients with developmental disabilities
      investigated whether exposure to parental anger and aggression was related to
      anger and assaultiveness in a hospital, controlling for background variables.
      Patient anger and aggression were assessed by self-report, staff-ratings, and
      archival records. Exposure to parental anger/aggression, assessed by a clinical
      interview, was significantly related to patient self-reported anger, staff-rated
      anger and aggression, and physical assaults in hospital, controlling for age,
      intelligence quotient, length of hospital stay, violent offense history, and
      childhood physical abuse. Results are consonant with previous findings concerning
      detrimental effects of witnessing parental violence and with the theory on
      acquisition of cognitive scripts for aggression. Implications for clinical
      assessment and cognitive restructuring in anger treatment are discussed.

PMID- 18338789
TI  - Mandibular arch muscle identity is regulated by a conserved molecular process
      during vertebrate development.
AB  - Vertebrate head muscles exhibit a highly conserved pattern of innervation and
      skeletal connectivity and yet it is unclear whether the molecular basis of their
      development is likewise conserved. Using the highly conserved expression of
      Engrailed 2 (En2) as a marker of identity in the dorsal mandibular muscles of
      zebrafish, we have investigated the molecular signals and tissues required for
      patterning these muscles. We show that muscle En2 expression is not dependent on
      signals from the adjacent neural tube, pharyngeal endoderm or axial mesoderm and
      that early identity of head muscles does not require bone morphogenetic pathway,
      Notch or Hedgehog (Hh) signalling. However, constrictor dorsalis En2 expression
      is completely lost after a loss of fibroblast growth factor (Fgf) signalling and
      we show that is true throughout head muscle development. These results suggest
      that head muscle identity is dependent on Fgf signalling. Data from experiments
      performed in chick suggest a similar regulation of En2 genes by Fgf signalling
      revealing a conserved mechanism for specifying head muscle identity. We present
      evidence that another key gene important in the development of mouse head
      muscles, Tbx1, is also critical for specification of mandibular arch muscle
      identity and that this is independent of Fgf signalling. These data imply that
      dorsal mandibular arch muscle identity in fish, chick and mouse is specified by a
      highly conserved molecular process despite differing functions of these muscles
      in different lineages.

PMID- 18338790
TI  - All vertebrates started out with a glial blood-brain barrier 4-500 million years
      ago.
AB  - All extant vertebrates have a blood-brain barrier (BBB), a specialized layer of
      cells that controls molecular traffic between blood and brain, and contributes to
      the regulation (homeostasis) of the brain microenvironment. Such homeostasis is
      critical for the stable function of synapses and neural networks. The barrier is
      formed by vascular endothelial cells in most groups, but by perivascular glial
      cells (astrocytes) in elasmobranch fish (sharks, skates, and rays). It has been
      unclear which is the ancestral form, but this information is important, as it
      could offer insights into the roles of the endothelium and perivascular glia in
      the modern mammalian BBB. We have used electron microscopic techniques to examine
      three further ancient fish groups, with intravascular horseradish peroxidase as
      permeability tracer. We find that in bichir and lungfish the barrier is formed by
      brain endothelial cells, while in sturgeon it is formed by a complex perivascular
      glial sheath, but with no detectable tight junctions. From their BBB pattern, and
      position on the vertebrate family tree, we conclude that the ancestral vertebrate
      had a glial BBB. This means that an endothelial barrier would have arisen
      independently several times during evolution, and implies that an endothelial
      barrier gave strong selective advantage. The selective advantage may derive
      partly from greater separation of function between endothelium and astrocytic
      glia. There are important implications for the development, physiology, and
      pathology of the mammalian BBB, and for the roles of endothelium and glia in CNS
      barrier layers.

PMID- 18338791
TI  - IGF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to
      progenitor cell proliferation in the subgranular layer of the dentate gyrus.
AB  - Adult progenitor cell proliferation in the subgranular zone (SGZ) of the dentate
      gyrus is a dynamic process that is modulated by an array of physiological
      process, including locomotor activity and novel environmental stimuli. In
      addition, pathophysiological events, such as ischemia and status epilepticus
      (SE), have been shown to stimulate neurogenesis. Currently, limited information
      is available regarding the extracellular stimuli, receptors, and downstream
      intracellular effectors that couple excitotoxic stimulation to progenitor cell
      proliferation. Here we show that pilocarpine-induced SE triggers a set of
      signaling events that impinge upon the p42/44 mitogen-activated protein kinase
      (MAPK) pathway to drive progenitor cell proliferation in the SGZ at 2-days post
      SE. Increased proliferation was dependent on insulin-like growth factor-1 (IGF
      1), which was localized to activated microglia near the SGZ. Using a combination
      of techniques, we show that IGF-1 is a CREB-regulated gene and that SE triggered
      CRE-dependent transcription in microglia at 2-days post-SE. Together, these data
      identify a potential signaling program that couples SE to progenitor cell
      proliferation. SE triggers CREB-dependent transcription in reactive microglia. As
      a CREB-target gene, IGF-1 expression is upregulated, and by 2-days post-SE, IGF-1
      triggers MAPK pathway activation in progenitor cells and, in turn, an increase in
      progenitor cell proliferation.

PMID- 18338792
TI  - Hyperoxia promotes astrocyte cell death after oxygen and glucose deprivation.
AB  - Astrocyte dysfunction and death accompany cerebral ischemia/reperfusion and
      possibly compromise neuronal survival. Animal studies indicate that neuronal
      death, neurologic injury, and oxidative molecular modifications are worse in
      animals exposed to hyperoxic compared to normoxic ventilation during reperfusion
      after global cerebral ischemia. It is unknown, however, whether ambient O2
      affects brain cell survival using in vitro ischemia paradigms where mechanisms of
      injury to specific cell types can be more thoroughly investigated. This study
      tested the hypothesis that compared with the supraphysiological level of 20% O2
      normally used in cell culture, lower, more physiological O2 levels protect
      astrocytes from death following oxygen and glucose deprivation. Primary rat
      cortical astrocytes were cultured under either 7 or 20% O2, exposed to O2, and
      glucose deprivation for 4 h, and then exposed to normal medium under either 7 or
      20% O2. Cell death and 3-nitrotyrosine and 8-hydroxy-2-deoxyguanosine
      immunoreactivities were assessed at different periods of reoxygenation.
      Astrocytes exposed to low levels of O2 during reoxygenation undergo less death
      and exhibit lower levels of protein nitration and nucleic acid oxidation when
      compared with those under high levels of O2 during reoxygenation. These results
      support the hypothesis that the 20% O2 normally used in cell culture exacerbates
      astrocyte death and oxidative stress in an in vitro ischemia/reperfusion model
      compared to levels that more closely approximate those that exist in vivo.

PMID- 18338793
TI  - Ca2+ entry through TRPC1 channels contributes to intracellular Ca2+ dynamics and
      consequent glutamate release from rat astrocytes.
AB  - Astrocytes can respond to a variety of stimuli by elevating their cytoplasmic
      Ca2+ concentration and can in turn release glutamate to signal adjacent neurons.
      The majority of this Ca2+ is derived from internal stores while a portion also
      comes from outside of the cell. Astrocytes use Ca2+ entry through store-operated
      Ca2+ channels to refill their internal stores. Therefore, we investigated what
      role this store-operated Ca2+ entry plays in astrocytic Ca2+ responses and
      subsequent glutamate release. Astrocytes express canonical transient receptor
      potential (TRPC) channels that have been implicated in mediating store-operated
      Ca2+ entry. Here, we show that astrocytes in culture and freshly isolated
      astrocytes from visual cortex express TRPC1, TRPC4, and TRPC5. Indirect
      immunocytochemistry reveals that these proteins are present throughout the cell;
      the predominant expression of functionally tested TRPC1, however, is on the
      plasma membrane. Labeling in freshly isolated astrocytes reveals changes in TRPC
      expression throughout development. Using an antibody against TRPC1 we were able
      to block the function of TRPC1 channels and determine their involvement in
      mechanically and agonist-evoked Ca2+ entry in cultured astrocytes. Blocking TRPC1
      was also found to reduce mechanically induced Ca2+-dependent glutamate release.
      These data indicate that Ca2+ entry through TRPC1 channels contributes to Ca2+
      signaling in astrocytes and the consequent glutamate release from these cells.

PMID- 18338794
TI  - Dystrophin-dependent and -independent AQP4 pools are expressed in the mouse
      brain.
AB  - In a recent study, we demonstrated that in the plasma membrane AQP4 is organized
      into several distinct large multisubunit complexes. In this study, we analysed
      whether these pools are similarly affected in dystrophin-deficient mice and
      immunolocalized the sites of dystrophin-dependent and -independent AQP4 pools.
      Western blot performed on two-dimensional Blue Native/SDS-PAGE membranes
      indicated that, among the AQP4 pools, it was mainly a large multisubunit complex
      that was specifically affected in dystrophin-deficient mice (DP71 and mdx3cv
      mice). This dystrophin-dependent AQP4 pool was immunolocalized in perivascular
      astrocytes, since it was found to be significantly altered in both types of
      dystrophin-deficient mice. Dystrophin-independent pools were immunolocalized in
      the granular cell layer of the cerebellum and in the subpial endfoot layer and
      ependymal cells in the brain. These data provide a better understanding on the
      association between AQP4 and the dystrophin-glycoprotein complex in the central
      nervous system.

PMID- 18338795
TI  - Hyperglycemia and downregulation of caveolin-1 enhance neuregulin-induced
      demyelination.
AB  - Neuregulins (NRGs) are growth factors which bind to Erb receptor tyrosine kinases
      that localize to Schwann cells (SCs). Although NRGs can promote cell survival,
      mitogenesis, and myelination in undifferentiated SCs, they also induce
      demyelination of myelinated co-cultures of SCs and dorsal root ganglion (DRG)
      neurons. We have shown previously that Erb B2 activity increased in
      premyelinating SCs in response to hyperglycemia, and that this correlated with
      the downregulation of the protein caveolin-1 (Cav-1). As myelinated SCs undergo
      substantial degeneration in diabetic neuropathy, we used myelinated SC/DRG neuron
      co-cultures to determine if hyperglycemia and changes in Cav-1 expression could
      enhance NRG-induced demyelination. In basal glucose, NRG1 caused a 2.4-fold
      increase in the number of damaged myelin segments. This damage reached 3.8-fold
      under hyperglycemic conditions, and was also associated with a robust decrease in
      the expression of Cav-1 and compact myelin proteins. The loss of Cav-1 and
      compact myelin proteins following hyperglycemia and NRG treatment was not due to
      neuronal loss, since the axons remained intact and there was no loss of PGP 9.5,
      an axonal marker protein. To examine if changes in Cav-1 were sufficient to alter
      the extent of NRG-induced demyelination, SC/DRG neurons co-cultures were infected
      with antisense or dominant-negative Cav-1(P132L) adenoviruses. Either antisense
      mediated downregulation or mis-localization of endogenous Cav-1 by Cav-1(P132L)
      resulted in a 1.5- to 2.4-fold increase in NRG-induced degeneration compared to
      that present in control cultures. These data support that hyperglycemia and
      changes in Cav-1 are sufficient to sensitize myelinated SC/DRG co-cultures to NRG
      induced demyelination.

PMID- 18338796
TI  - Region-specific expression of immunoregulatory proteins on microglia in the
      healthy CNS.
AB  - In accordance with a high degree of spatial organization in the central nervous
      system (CNS), most CNS diseases display a regional distribution. Although
      microglia have been established as key players in various CNS diseases, it is not
      yet clear whether microglia display region-specific properties. Therefore, this
      study aimed to evaluate the existence of distinct microglia phenotypes in various
      regions of the healthy, adult mouse CNS. Using ex vivo flow cytometric analysis
      surface expression of CD11b, CD40, CD45, CD80, CD86, F4/80, TREM-2b, MHCII,
      CXCR3, CCR9, and CCR7 were analyzed. Most of these immunoregulatory markers were
      found on microglia and showed significant region-specific differences in
      expression levels. These findings considerably corroborate the existence of
      immunological diversity among microglia in the healthy, unchallenged CNS of adult
      mice.

PMID- 18338797
TI  - Analysis of neural potential of human umbilical cord blood-derived multipotent
      mesenchymal stem cells in response to a range of neurogenic stimuli.
AB  - We investigated the neurogenic potential of full-term human umbilical cord blood
      (hUCB)-derived multipotent mesenchymal stem cells (MSCs) in response to neural
      induction media or coculture with rat neural cells. Phenotypic and functional
      changes were assessed by immunocytochemistry, RT-PCR, and whole-cell patch-clamp
      recordings. Naive MSCs expressed both mesodermal and ectodermal markers prior to
      neural induction. Exposure to retinoic acid, basic fibroblast growth factor, or
      cyclic adenosine monophosphate (cAMP) did not stimulate neural morphology,
      whereas exposure to dibutyryl cAMP and 3-isobutyl-1-methylxanthine stimulated a
      neuron-like morphology but also appeared to be cytotoxic. All protocols
      stimulated increases in expression of the neural precursor marker nestin, but
      expression of mature neuronal or glial markers MAP2 and GFAP was not observed.
      Nestin expression increases were serum level dependent. Electrophysiological
      properties of MSCs were studied with whole-cell patch-clamp recordings. The MSCs
      possessed no ionic currents typical of neurons before or after neural induction
      protocols. Coculture of hUCB-derived MSCs and rat neural cells induced some MSCs
      to adopt an astrocyte-like morphology and express GFAP protein and mRNA. Our data
      suggest hUCB-derived MSCs do not transdifferentiate into mature functioning
      neurons in response to the above neurogenic protocols; however, coculture with
      rat neural cells led to a minority adopting an astrocyte-like phenotype.

PMID- 18338798
TI  - Impaired activation of celiac ganglion neurons in vivo after damage to their
      sympathetic nerve terminals.
AB  - Because damage to sympathetic nerve terminals occurs in a variety of diseases, we
      tested the hypothesis that nerve terminal damage per se is sufficient to impair
      ganglionic neurotransmission in vivo. First, we measured the effect of nerve
      terminal damage produced by the sympathetic nerve terminal toxin 6
      hydroxydopamine (6-OHDA) on ganglionic levels of several neurotrophins thought to
      promote neurotransmission. 6-OHDA-induced nerve terminal damage did not decrease
      the expression of neurotrophin-4 or brain-derived neurotrophic factor mRNA in the
      celiac ganglia but did decrease the ganglionic content of both nerve growth
      factor protein (nadir = -63%) and the mRNA of the alpha-3 subunit of the
      nicotinic cholinergic receptor (nadir = -49%), a subunit required for
      neurotransmission. Next, we tested whether this degree of receptor deficiency was
      sufficient to impair activation of celiac ganglia neurons. Impaired fos mRNA
      responses to nicotine administration in the celiac ganglia of 6-OHDA-pretreated
      rats correlated temporally with suppressed expression of functional nicotinic
      receptors. We verified by Fos protein immunohistochemistry that this ganglionic
      impairment was specific to principal ganglionic neurons. Last, we tested whether
      centrally initiated ganglionic neurotransmission is also impaired following nerve
      terminal damage. The principal neurons in rat celiac ganglia were reflexively
      activated by 2-deoxy-glucose-induced glucopenia, and the Fos response in the
      celiac ganglia was markedly inhibited by pretreatment with 6-OHDA. We conclude
      that sympathetic nerve terminal damage per se is sufficient to impair ganglionic
      neurotransmission in vivo and that decreased nicotinic receptor production is a
      likely mediator.

PMID- 18338799
TI  - Cell-specific actions of HIV-Tat and morphine on opioid receptor expression in
      glia.
AB  - HIV-1 patients who abuse opiate-based drugs, including heroin and morphine, are
      at a higher risk of developing HIV dementia. The effects of opiates are mediated
      predominantly through opioid receptors, which are expressed on glial cells. As
      HIV-1 infection in the CNS is restricted to glial cells, experiments were
      designed to measure the cell-specific effects of HIV Tat and morphine exposure on
      opioid receptor expression in both astrocytes and microglia. Specifically, the
      cell-type-specific pattern of mu opioid receptor (MOR), delta opioid receptor
      (DOR), and kappa opioid receptor (KOR) localization (surface vs. intracellular)
      and expression of opioid receptor mRNA were determined after exposure to morphine
      in the presence and the absence of Tat in primary cultured microglia and
      astrocytes. Data show that morphine treatment caused significantly decreased cell
      surface expression of opioid receptors in microglia but not in astrocytes.
      However, morphine treatment in the presence of Tat significantly increased
      intracellular expression of opioid receptors and prevented morphine-induced cell
      surface opioid receptor down-regulation in microglia. These findings document
      that cell surface opioid receptor expression is divergently regulated by morphine
      in microglia compared with in astrocytes, and further suggest that HIV-Tat could
      exacerbate opioid receptor signaling in microglia by increasing receptor
      expression and/or altering ligand-induced trafficking of opioid receptors.

PMID- 18338800
TI  - Regional-specific regulation of BDNF and trkB correlates with nigral dopaminergic
      cell sprouting following unilateral nigrostriatal axotomy.
AB  - Axotomy is a powerful stimulus of axon growth and plastic changes. We
      investigated the potential role of BDNF/trkB signaling in the sprouting of
      dopaminergic nigral axons in response to axotomy of the medial forebrain bundle.
      Tyrosine hydroxylase immunohistochemistry revealed the existence of sprouting
      mechanisms in the axotomized substantia nigra (SN). Time-course changes of trkB
      mRNA expression demonstrated a robust increase in an area projecting from the
      rostral tip of the SN to the glial scar, which coincided with evidence of nigral
      dopaminergic sprouting. In addition, we found an early loss of this messenger in
      areas related to the knife cut, which recovered by 7 days postlesion. TrkB down
      regulation appeared to be associated to the lesion-induced local damage, as it
      was restricted to an area showing Fluoro-Jade B- and TUNEL positive cells. In
      trkB-depleted areas, an inverse correlation between mRNA expressions of BDNF and
      trkB was apparent. Specific induction of BDNF mRNA was mostly seen in border of
      areas devoid of trkB mRNA. In contrast, in the areas exhibiting trkB mRNA
      expression, no BDNF mRNA was detected. We suggest that trkB levels could be a
      determinant element in regulating BDNF expression. Finally, the search for
      molecules involved in either promoting or inhibiting axonal growth, demonstrated
      up-regulation of GAP-43 and Nogo-A mRNA at sites close to the knife transections
      as early as 1 day postlesion. However, overall, Nogo-A induction was more robust
      than that seen for GAP-43.

PMID- 18338801
TI  - Molecular biology changes associated with LRRK2 mutations in Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal
      loss in the substantia nigra. The recent discovery of leucine-rich-repeat kinase
      2 gene (LRRK2) mutations in PD is significant because these mutations are the
      most common cause of autosomal dominant PD. Furthermore, a common recurrent
      mutation (G2019S) is associated with a significant proportion of nonfamilial PD,
      and a polymorphic variant (G2385R) has been found to increase the risk in the
      Asian race. The large LRRK2 protein of 280 kD contains three protein-protein
      interaction domains and two enzymatic domains, the Ras-related GTPase and the
      kinase. Mutations in these domains have been described in PD patients.
      Preliminary evidence suggests that some types of LRRK2 mutations increase the
      kinase activity, and this is associated with significantly higher apoptotic cell
      death in dopaminergic cell lines and primary neurons; abolishing the kinase
      function ameliorates this cellular toxicity. It also appears that its GTPase
      domain can be activated independently, whereas the kinase activity strictly
      requires the GTPase activation. Mutations in the LRRK2 have displayed notable
      pleomorphic pathologies that might indicate an upstream role of LRRK2 in cellular
      signaling pathways. The identification of physiological substrates (likely to be
      involved in signaling and apoptotic pathways) of LRRK2 remains an important step
      in our understanding of the role of LRRK2 in the disease process. Further in
      vitro and in vivo studies will unravel the role of LRRK2 in cell signaling and
      its impact on proliferation, differentiation, and survival of neurons.

PMID- 18338802
TI  - Bilirubin as an endogenous modulator of neurotrophin redox signaling.
AB  - Bilirubin is neurotoxic upon excess accumulation in the brain, but it also plays
      important physiological roles related to its antioxidant properties. Here we
      report that exposure of PC12 and primary rat cerebellar granule neurons to
      bilirubin (0.5-10 microM) drastically decreases nerve growth factor (NGF)/brain
      derived neurotrophic factor signaling to Akt and extracellular signal-regulated
      kinases (ERKs), indicating a direct interference of the molecule with crucial
      prosurvival signaling pathways. This effect likely involves the scavenging
      capacity of bilirubin, the latter being able to inhibit, in PC12 cells,
      accumulation of intracellular reactive oxygen species and phosphorylation of Akt
      and ERKs in response to extracellular hydrogen peroxide. Interestingly, in the
      absence of exogenous growth factor, bilirubin elicited the phosphorylation of
      ERKs and of the cAMP responsive element binding (CREB) transcription factor, a
      signature of NGF-dependent survival signaling. These growth factor-like signaling
      effects were paralleled by the induction of the neuronal nitric oxide synthase
      (nNOS) and generation of nitric oxide (NO). Pharmacological dissection of the
      signaling cascade triggered by bilirubin revealed that phosphorylation of ERKs
      requires NO signaling through soluble guanylyl cyclase, and, further upstream,
      influx of extracellular calcium is necessary for nNOS induction and NO release,
      likely through calcium-dependent phosphorylation of CREB. Importantly, the
      cascade elicited by bilirubin through NO and ERK is cytoprotective, as revealed
      by exacerbated bilirubin toxicity in cultures treated by either NOS or MEK
      inhibitors. Taken together, these observations indicate an important action of
      bilirubin on redox signaling by neurotrophins, with either inhibitory or
      agonistic effects based on growth factor availability.

PMID- 18338803
TI  - Decreased drebrin mRNA expression in Alzheimer disease: correlation with tau
      pathology.
AB  - To investigate the mRNA expression of the dendritic spine protein drebrin in
      Alzheimer's disease (AD), we performed post-mortem in situ hybridization studies
      in brain sections from 20 AD patients and 21 controls. AD diagnosis was confirmed
      by decreased drebrin protein and increased Abeta(40) (+464%; P < 0.05), Abeta(42)
      (+369%; P < 0.0001), Abeta(42/40) ratio (+226%; P < 0.01), total tau (+2,725%; P
      < 0.0001), and paired helical filament tau (PHFtau; +867%; P < 0.001) compared
      with controls. We found significant decreases in drebrin mRNA in the parietal
      cortex (-27%; P < 0.01), the temporal cortex (-22%; P < 0.05), and the
      hippocampus (-25%; P < 0.05) of AD patients compared with controls. Cortical
      levels of drebrin mRNA correlated positively with soluble total tau (r(2) =
      +0.244) but negatively with duration of symptoms (r(2) = -0.357) and PHFtau (r(2)
      = -0.248). Drebrin mRNA levels were correlated to a lesser degree with the
      drebrin protein content (r(2) = +0.136) and with sim2 (r(2) = +0.176), a
      potential modulator of drebrin transcription. Our results suggest that the down
      regulation of drebrin mRNA expression plays an important role in AD and is
      closely related to the progression of the disease.

PMID- 18338804
TI  - Inhibitors of p38 mitogen-activated protein kinase enhance proliferation of mouse
      neural stem cells.
AB  - The p38 mitogen-activated protein kinase (MAPK) is induced in response to
      environmental stress. Although p38 MAPK has been implicated in diverse cellular
      processes, including cell proliferation, differentiation, and survival of
      differentiated cells in the central nervous system (CNS), the expression profile
      and roles of p38 MAPK in the developing brain remain largely unknown. In the
      present study, we demonstrate that p38 MAPK is expressed predominantly in nestin
      positive cells in the cerebral cortex in embryonic day 10 (E10) brain and that
      expression of the protein decreases gradually during development. To investigate
      the roles of p38 MAPK in the embryonic brain, two selective p38 MAPK inhibitors,
      SB202190 and SB203580, were added to the primary neuronal cultures from E10-E14
      brains. After 7 days of exposure to these inhibitors, but not SB202474, a
      negative analog of SB203580, numerous large neurospheres were present. MAPK
      inhibitors also selectively increased the growth rate of neural stem cells (NSCs)
      purified from secondary neurospheres and the number of bromodeoxyuridine-positive
      NSCs. Thus, p38 MAPK inhibitors are potent stimulators of NSC proliferation, and
      p38 MAPK may be an intrinsic negative regulator of NSC proliferation during early
      brain development.

PMID- 18338805
TI  - Polyurethane intravaginal ring for controlled delivery of dapivirine, a
      nonnucleoside reverse transcriptase inhibitor of HIV-1.
AB  - Women-controlled methods for prevention of male-to-female sexual transmission of
      HIV-1 are urgently needed. Providing inhibitory concentrations of HIV-1 reverse
      transcriptase inhibitors to impede the replication of the virus in the female
      genital tissue offers a mechanism for prophylaxis of HIV-1. To this end, an
      intravaginal ring device that can provide long duration delivery of dapivirine, a
      nonnucleoside reverse transcriptase inhibitor of HIV-1, was developed utilizing a
      medical-grade polyether urethane. Monolithic intravaginal rings were fabricated
      and sustained release with cumulative flux linear with time was demonstrated
      under sink conditions for a period of 30 days. The release rate was directly
      proportional to the amount of drug loaded. Another release study conducted for a
      week utilizing liposome dispersions as sink conditions, to mimic the partitioning
      of dapivirine into vaginal tissue, also demonstrated release rates constant with
      time. These results qualify polyether urethanes for development of intravaginal
      rings for sustained delivery of microbicidal agents.

PMID- 18338806
TI  - Cannabidiol: a prion therapy for mice?

PMID- 18338807
TI  - Structural, thermodynamic, and kinetic aspects of the trimorphism of
      hydrocortisone.
AB  - Hydrocortisone was investigated for polymorphism and pseudopolymorphism and three
      different polymorphic modifications (I-III) and one 2-propanol solvate were
      found. Forms I and III crystallize in the orthorhombic space group P2(1)2(1)2(1),
      whereas form II and the 2-propanol solvate crystallize monoclinic in space group
      P2(1). In all the modifications the molecules are connected by intermolecular O-
      H...O hydrogen bonding. In the 2-propanol solvate, channels are formed in which
      the solvent molecules are embedded. Solvent-mediated conversion experiments
      reveal that the commercially available form I represents the thermodynamically
      most stable modification at room temperature, whereas forms II and III are
      metastable. On heating, form III transforms into form II in an endothermic
      reaction, which shows that an enantiotropic relationship exists between these
      forms. Form I exhibits the highest melting point and the highest heat of fusion
      and thus represents the thermodynamically most stable form over the whole
      temperature range. DSC measurements indicate that form I behaves monotropic to
      forms II and III. Desolvation of the 2-propanol solvate at higher temperatures
      results in a transformation into form II, whereas the removal of 2-propanol at
      room temperature and in vacuum reduced pressure leads to the formation of form
      III.

PMID- 18338808
TI  - Adsorption and function of recombinant factor VIII at solid-water interfaces in
      the presence of Tween-80.
AB  - The adsorption, structural alteration and biological activity of a recombinant
      Factor VIII was investigated in the presence of the surfactant Tween-80, at
      hydrophilic and hydrophobic solid-water interfaces. Hydrophilic and silanized,
      hydrophobic silica surfaces were used as substrates for protein and surfactant
      adsorption, which was monitored in situ, with ellipsometry. At the hydrophobic
      surface, the presence of Tween in the protein solution resulted in a reduction in
      amount of protein adsorbed, while rFVIII adsorption at the hydrophilic surface
      was entirely unaffected by the presence of Tween. These observations were
      attributed to high binding strength between Tween and the hydrophobic surface,
      and low binding strength between Tween and the hydrophilic surface. Colloidal
      particles bearing hydrophilic and hydrophobic surfaces, and net positive or
      negative surface charge, were used as substrates for rFVIII adsorption in
      evaluation of tertiary structure change and biological activity retention at
      interfaces. Fluorescence emission spectroscopy showed that rFVIII tertiary
      structure was changed upon exposure to hydrophobic nanoparticle surfaces.
      Similarly, the biological activity of rFVIII (based on the activated partial
      thromboplastin time) was reduced at hydrophobic surfaces. At high surfactant
      concentration, these properties were better preserved. This was attributed to
      Tween adsorption sterically inhibiting rFVIII adsorption. While hydrophilic
      surfaces were associated with relatively high rFVIII adsorption, they did not
      induce large changes in structure or activity. This was attributed to the
      formation of a tightly packed, ordered adsorbed layer on these surfaces, governed
      by electrostatic attraction and not mediated by the rFVIII active site.

PMID- 18338809
TI  - Experience with 31 sentinel lymph node biopsies for sarcomas and carcinomas in
      pediatric patients.
AB  - BACKGROUND: Few data exist regarding techniques, indications, and outcomes for
      sentinel lymph node biopsy in pediatric patients with sarcomas and carcinomas.
      METHODS: A retrospective 10-year review was conducted, with Institutional Review
      Board waiver, of the pathology, lymphoscintigraphy, and clinical records for all
      pediatric patients selected to undergo sentinel lymph node biopsy at a major
      cancer center. RESULTS: Thirty-one sentinel lymph node biopsies were performed in
      30 pediatric patients (median age, 12 years; range, 2-21 years). With the
      administration of technetium 99m sulfur colloid, sentinel lymph nodes were
      identified preoperatively in 30 of 31 cases, and intraoperatively in the
      remaining case. Radiotracer alone was used in 13 of 31 cases but was supplemented
      with isosulfan blue dye in the remaining 18 cases. There were no complications.
      Positive sentinel lymph nodes occurred in 1 of 9 patients with rhabdomyosarcoma
      and in 2 of 5 patients with breast cancer, and in both of these diseases the
      sentinel lymph node results helped guide treatment decisions. No other patients
      had positive sentinel lymph nodes, and among those with nonrhabdomyosarcoma soft
      tissue sarcomas there were no lymph node basin recurrences despite a lack of
      lymph node basin irradiation or formal lymph node dissection. The median follow
      up was 48 months (range, 0-111 months). CONCLUSIONS: Sentinel lymph node biopsy
      for pediatric soft-tissue tumors can be performed safely, and the results can
      alter treatment decisions both for children with rhabdomyosarcoma and adolescents
      with breast cancer. In patients with nonrhabdomyosarcoma soft-tissue sarcoma, we
      observed no positive sentinel lymph nodes and no lymph node basin recurrences;
      these data should prompt the prospective study of sentinel lymph node biopsy as a
      modality that might help guide the administration or withholding of regional
      therapy among pediatric patients with nonrhabdomyosarcoma soft-tissue sarcoma.

PMID- 18338810
TI  - Cardiovascular risk in long-term survivors of testicular cancer.
AB  - BACKGROUND: Long-term survivors of testicular cancer (TC) who received cisplatin
      based chemotherapy have an increased risk of cardiovascular disease. A cross
      sectional study was performed to objectively assess cardiovascular risk,
      subclinical atherosclerosis, and endothelial function in long-term survivors of
      TC. METHODS: Long-term survivors of TC underwent evaluation including
      determination of body mass index (BMI), Framingham relative risk (RR), brachial
      artery flow-mediated dilatation (FMD), carotid artery intima-media thickness
      (IMT), soluble intercellular adhesion molecule-1 (sICAM-1), high sensitivity C
      reactive protein (hs-CRP), and flow cytometric analysis of peripheral blood for
      levels of endothelial progenitor cells (EPCs) and circulating endothelial cells
      (CECs). TC survivors who received chemotherapy were compared with a chemotherapy
      naive cohort. RESULTS: Twenty-four patients received cisplatin-based chemotherapy
      (CBCT) and 15 were chemotherapy-naive (CN). The CBCT cohort demonstrated more
      impairment of brachial artery FMD than the CN group (5.6% vs 8.8%; P = .05). The
      mean sICAM was also found to be higher in the CBCT cohort compared with the CN
      group (P = .04). No significant differences between the groups were noted with
      regard to BMI, Framingham RR, carotid IMT, or hs-CRP. In a subset of patients, TC
      survivors who received chemotherapy had a significantly increased level of CECs
      compared with CN patients (P = .04). No significant difference in EPC levels was
      detected. CONCLUSIONS: Long-term survivors of TC who received chemotherapy
      demonstrate objective evidence of endothelial injury and dysfunction, a potential
      mechanism for increased cardiovascular risk.

PMID- 18338811
TI  - Surgical versus radiographic determination of para-aortic lymph node metastases
      before chemoradiation for locally advanced cervical carcinoma: a Gynecologic
      Oncology Group Study.
AB  - BACKGROUND: Patients with cervical cancer who had negative para-aortic lymph
      nodes (PALNs) identified by pretreatment surgical staging were compared with
      patients who had only radiographic exclusion of PALN metastases before they
      received treatment with pelvic radiation and brachytherapy (RT) plus cisplatin
      (C)-based chemotherapy. METHODS: Patients who participated in 1 of 3 Phase III
      Gynecologic Oncology Group (GOG) trials (GOG 85, GOG 120, and GOG 165) and who
      were assigned randomly to receive either RT plus C or RT plus C combined with 5
      fluorouracil with or without hydroxyurea comprised this retrospective analysis.
      Patients who had negative PALN status determined by surgical sampling (mandatory
      in GOG 85 and GOG 120 and optional in GOG 165) were compared with patients who
      had negative PALN status determined radiographically (GOG 165). RESULTS: Five
      hundred fifty-five patients underwent surgical PALN sampling (the S group), and
      130 patients underwent radiographic evaluation only (the R group). Age, race,
      histology, and tumor grade were similar. Patients in the R group had better
      performance status (P < .01), less advanced stage (P = .023), and smaller tumor
      size (P = .004) compared with patients in the S group, although patients with
      stage III and IV disease in the S group had better 4-year progression-free
      survival (48.9% vs 36.3%) and overall survival (54.3% vs 40%) compared with
      patients in the R group. In multivariate analysis, the R group was associated
      independently with a poorer prognosis compared with the S group (for disease
      progression: hazard ratio [HR], 1.35, 95% confidence interval [95% CI], 1.01
      1.81; for death: HR, 1.46, 95% CI, 1.08-1.99). CONCLUSIONS: Surgical exclusion
      (compared with radiographic exclusion) of positive PALNs in patients with
      cervical cancer who received chemoradiation (RT plus C-based chemotherapy) had a
      significant prognostic impact.

PMID- 18338812
TI  - Platelet-derived growth factor receptor as a prognostic marker and a therapeutic
      target for imatinib mesylate therapy in osteosarcoma.
AB  - The purpose of this review was to determine whether imatinib mesylate (STI571,
      Gleevec) has a role in the treatment of osteosarcoma. The expression of platelet
      derived growth factor (PDGF) receptor and its ligand was examined in a panel of
      surgical specimens obtained from 54 osteosarcoma patients, and then the
      expression was compared with prognosis. The effects of imatinib mesylate on
      growth and molecular events in 10 patient-derived osteosarcoma cell cultures were
      investigated. Immunohistochemical studies demonstrated frequent expression of
      PDGF-AA (80.4%) and PDGF-alpha receptor (79.6%) and their correlation with
      inferior event-free survival (P < .05). PDGF-B-B and PDGF-beta-receptor
      expressions were also frequent (75.4% and 86%, respectively); however,
      statistically significant inferior event-free survival was not demonstrated (P =
      .15). In vitro studies demonstrated that imatinib mesylate had a variable
      cytotoxic effect on various osteosarcoma primary cultures, with an IC(50) of 5.6
      microM to 9.5 microM, and blocked the PDGF-induced intracellular signal
      transduction as well as inhibition of downstream Akt phosphorylation. Mitogen
      activated protein kinase (MAPK) was constitutively activated despite PDGF
      stimulation and imatinib mesylate treatment in 7 of 10 osteosarcoma cultures,
      perhaps explaining uncontrolled proliferation and relative unresponsiveness to
      imatinib. Imatinib mesylate could not be viewed as having a role as a single
      agent at current conventional doses for the treatment of osteosarcoma. These
      findings predicted activity in osteosarcoma clinical trials and suggested that in
      vitro model systems predict clinical behavior and that PDGF and its receptor
      expression could potentially be used for determining prognosis of osteosarcoma.

PMID- 18338813
TI  - Breast cancer adjuvant chemotherapy dosing in obese patients: dissemination of
      information from clinical trials to clinical practice.
AB  - BACKGROUND: Substantial variation in adjuvant breast cancer chemotherapy dosing
      in obese women suggests that there is uncertainty about optimal practices. The
      purpose of this study was to investigate variations in dose determinations in
      clinical trial protocols and publications over the last 3 decades as potential
      sources of this uncertainty. METHODS: The National Cancer Institute database was
      used to identify protocols of breast cancer adjuvant chemotherapy conducted by
      cooperative groups between 1970-2000, and these protocols were then obtained
      directly from the cooperative groups. Dose determinations were categorized in
      each protocol and in published reports from each clinical trial. Fisher exact
      tests were used to compare the proportions of protocols that used full weight
      based doses over time. RESULTS: Protocol-specified chemotherapy dosing was
      obtained for all of 44 eligible trials. A significant increase was identified in
      the use of full weight-based doses in the later time period compared with the
      earlier (P = .004; 2-sided Fisher exact test). A notable exception was 1
      cooperative group that continues to require dose limitations for doxorubicin and
      cyclophosphamide in patients with a body surface area of more than 2.0 m(2).
      Regardless of publication date, published reports of clinical trials rarely
      provide information on use of full or limited weight-based doses. CONCLUSIONS:
      Variations in dose determinations among clinical trial protocols and lack of
      information on use of full weight-based doses in most publications are 2 likely
      sources of variation in chemotherapy dosing in obese women. Developing consensus
      and disseminating information on optimal chemotherapy dosing will likely reduce
      such variation and may improve survival among obese patients with breast cancer.

PMID- 18338814
TI  - Pretreatment prostate-specific antigen velocity is associated with development of
      distant metastases and prostate cancer mortality in men treated with radiotherapy
      and androgen-deprivation therapy.
AB  - BACKGROUND: In men with prostate cancer, pretreatment prostate-specific antigen
      (PSA) velocity (PSAV) has been demonstrated as a predictor of biochemical and
      survival outcomes in patients undergoing radical prostatectomy (RP). The utility
      of pretreatment PSAV in predicting outcomes after radiotherapy (RT), with or
      without androgen-deprivation therapy (ADT), is less certain. This study was
      undertaken to determine whether pretreatment PSAV is associated with biochemical
      disease-free survival, patterns of recurrence, and survival outcomes in men
      treated with radiation therapy and ADT. METHODS: Two hundred seventy-seven
      patients with intermediate- and high-risk prostate cancer treated with RT and ADT
      formed the study cohort. Kaplan-Meier survival estimates and Cox regression
      analyses were used to evaluate whether PSAV was associated with disease outcomes.
      RESULTS: The median age of diagnosis was 70 years, and the median follow-up was
      6.8 years. Men with a PSAV in the highest quartile tended to have higher risk
      disease at presentation (P = .028). After adjustment for known prognostic factors
      and duration of ADT, men who had a PSAV in the highest quartile had an increased
      risk of distant metastasis (hazard ratio [HR], 4.0; 95% confidence interval [95%
      CI], 1.61-9.9 [P = .003]) and prostate cancer-specific mortality (HR, 2.75; 95%
      CI, 1.27-5.95 [P = .01]) compared with men who had a lower PSAV, but had no
      increase in the risk of local recurrence (P = .76). CONCLUSIONS: A high
      pretreatment PSAV was associated with distant metastasis and prostate cancer
      specific mortality but not with local recurrence. A high pretreatment PSAV may
      signify the presence of occult metastatic disease. Randomized trials are needed
      to determine whether more aggressive intervention is required in men who present
      with high pretreatment PSAV.

PMID- 18338815
TI  - Systemic therapy for metastatic colorectal cancer: current questions.
AB  - A proliferation of new cytotoxic and biologic agents has led to improved survival
      in patients with metastatic colorectal cancer (mCRC). The ability of surgery to
      increase long-term survival in patients with liver and/or lung metastases also
      has been firmly established. It has become increasingly difficult as the numbers
      and types of treatment options have expanded to identify optimal drug
      combinations, sequences, and duration and the best way to integrate systemic
      chemotherapy with potentially curative surgery for metastatic lesions. For this
      review, the authors examined how recent clinical trials have addressed some
      pertinent questions regarding the use of systemic chemotherapy and biologic
      agents in patients with mCRC.

PMID- 18338816
TI  - Pivotal role of early B-cell factor 1 in development of striatonigral medium
      spiny neurons in the matrix compartment.
AB  - The mammalian striatum plays a critical function in motor control, motor and
      reward learning, and cognition. Dysfunction and degeneration of the striatal
      neurons are implicated in major neurological and psychiatric disorders. The vast
      majority of striatal neurons are medium spiny neurons (MSNs). MSNs can be further
      subdivided into distinct subtypes based on their physical localization in the
      striatal patch vs. matrix compartments and based on their axonal projections and
      marker gene expression (i.e., striatonigral MSNs vs. striatopallidal MSNs).
      Despite our extensive knowledge on the striatal cytoarchitecture and circuitry,
      little is known about the molecular mechanisms controlling the development of the
      MSN subtypes in the striatum. Early B-cell factor 1 (Ebf1) is a critical
      transcription factor implicated in striatal MSN development. One study shows that
      Ebf1 is critical for the differentiation of MSNs in the matrix, and our separate
      study demonstrates that Ebf1 is selectively expressed in the striatonigral MSNs
      and is essential for their postnatal differentiation. In the present study, we
      further validate the striatonigral MSN deficits in Ebf1(-/-) mice using multiple
      striatonigral MSN reporter mice. Moreover, we demonstrate that the striatonigral
      MSN deficits in these mice are restricted to those in the matrix, with relative
      sparing of those in the patch. Finally, we demonstrate that Ebf1 deficiency also
      results in reduced expression of another striatonigral-specific transcription
      factor, zinc finger binding protein 521 (Zfp521), which is a known Ebf1
      functional partner. Overall, our study reveals that Ebf1 may play an essential
      role in controlling the differentiation of the striatonigral MSNs in the matrix
      compartment.

PMID- 18338817
TI  - Dual ERK and phosphatidylinositol 3-kinase pathways control airway smooth muscle
      proliferation: differences in asthma.
AB  - Hyperplasia of airway smooth muscle (ASM) within the bronchial wall of asthmatic
      patients has been well documented and is likely due to increased muscle
      proliferation. We have shown that ASM cells obtained from asthmatic patients
      proliferate faster than those obtained from non-asthmatic patients. In ASM from
      non-asthmatics, mitogens act via dual signaling pathways (both ERK- and PI 3
      kinase-dependent) to control growth. In this study we are the first to examine
      whether dual pathways control the enhanced proliferation of ASM from asthmatics.
      When cells were incubated with 0.1% or 1% FBS, ERK activation was significantly
      greater in cells from asthmatic subjects (P < 0.05). In contrast, when cells were
      stimulated with 10% FBS, ERK activity was significantly greater in the non
      asthmatic cells. However, cell proliferation in asthmatic cells was still
      significantly higher in cells stimulated by both 1% and 10% FBS. Pharmacological
      inhibition revealed that although dual proliferative pathways control ASM growth
      in cells from non-asthmatics stimulated with 10% FBS to an equal extent ([(3)H]
      thymidine incorporation reduced to 57.2 +/- 6.9% by the PI 3-kinase inhibitor
      LY294002 and 57.8 +/- 1.1% by the ERK-pathway inhibitor U0126); in asthmatics,
      the presence of a strong proliferative stimulus (10% FBS) reduces ERK activation
      resulting in a shift to the PI 3-kinase pathway. The underlying mechanism appears
      to be upregulation of an endogenous MAPK inhibitor--MKP-1--that constrains ERK
      signaling in asthmatic cells under strong mitogenic stimulation. This study
      suggests that the PI 3-kinase pathway may be an attractive target for reversing
      hyperplasia in asthma.

PMID- 18338818
TI  - Matrix stiffness and serum concentration effects matrix remodelling and ECM
      regulatory genes of human bone marrow stem cells.
AB  - The effects of mechanical stimulation of cell-seeded collagen constructs on cell
      orientation, intracellular signalling and molecular responses have been widely
      reported. In this study we investigated in vitro the contractile responses of
      human bone marrow stem cells (HBMSCs) to increasing collagen gel substrate
      stiffness and their effect on extracellular matrix (ECM) regulatory genes. Human
      dermal fibroblasts (HDFs) were used as controls. Cells were cultured in 10% and
      20% FCS and embedded in collagen constructs at a density of 1 million cells/ml
      collagen. Matrix stiffness was achieved by subjecting the constructs to three
      different strain regimes (0%, 5% and 10%), using a computer-driven tensional
      culture force monitor (t-CFM) capable of uniaxial loading. The contraction forces
      generated by the cells were quantified over 24 h. Molecular outputs were
      quantified using RT-PCR. HBMSCs significantly increased force generation to
      increasing serum concentration (i.e 10% to 20%). 10% FCS concentration
      significantly reduced contraction as pre-strain stiffness was increased in HBMSCs
      and HDFs (0% > 5% > 10%). However, at 20% FCS HBMSCs generated similar peak force
      contraction at 24 h to 5% and 10% pre-strain (0% = 5% = 10%). The ECM regulatory
      gene for MMP2 showed upregulation at 5% pre-strain, but a 50% downregulation when
      pre-strain was increased to 10%. MMP9 was upregulated at 5% pre-strain and
      further upregulated at 10% pre-strain. In designing tissue-engineering solutions,
      predictable responses of cells, embedded within bio-artificial matrices, to
      external mechanical forces are critical. To take into account the increasing
      stiffness of the matrix as increasing ECM is deposited, it would be necessary to
      take mechanical stimulation into account to determine predictable cellular
      responses.

PMID- 18338819
TI  - Gene transfer into guinea pig cochlea using adeno-associated virus vectors.
AB  - BACKGROUND: Several genes are candidates for treating inner ear diseases. For
      clinical applications, minimally invasive approaches to the inner ear are
      desirable along with minimal side-effects. METHODS: Adeno-associated virus (AAV)
      was used as a vector into the guinea pig inner ear. Six AAV-cytomegalovirus
      hybrids (AAV-2/1, -2/2, -2/5, -2/7, -2/8 and -2/9) were infused into perilymph of
      the cochlea basal turn, an approach that could be used in cochlear implant
      surgery. At 7 days after injection, distribution of gene expression, hearing and
      morphology were evaluated. Adenoviral vector was also used to compare
      distributions of gene expression. Moreover, distribution of cell surface
      receptors of AAV in the cochlea was examined using immunohistochemistry. RESULTS:
      Using the perilymphatic approach, adenovirus could be transferred to mesothelial
      cells lining the perilymph, but not sensory cells. Conversely, all AAV serotypes
      displayed tissue tropism to inner hair cells, with AAV-2/2 showing particularly
      efficient transfer to sensory cells. This tissue tropism of AAV could not be
      explained by the distribution of AAV receptors. Hearing and morphology were
      largely unaffected. CONCLUSIONS: Our results indicate that AAV vector can be
      safely applied to the inner ear and AAV-2/2 offers a good tool for transferring
      transgenes into sensory cells of the inner ear efficiently without toxicity.

PMID- 18338820
TI  - Activation of tumor-specific T cells by dendritic cells expressing the NY-ESO-1
      antigen after transfection with the cationic lipophosphoramide KLN5.
AB  - BACKGROUND: Genetic modification of human monocyte-derived dendritic cells (DC)
      with cDNA sequences encoding tumor-associated antigens (TAA) is a promising
      strategy for cancer immunotherapy. The present study aimed to develop a nonviral
      gene transfer method based on the use of the cationic lipophosphoramide reagent,
      KLN-5, as an alternative to the commonly used viral vectors. METHODS: First, the
      efficiency of KLN5 for gene transfection into DC was investigated using the green
      fluorescent protein (GFP) reporter gene. The highest transfection efficiency/cell
      viability ratio was determined by flow cytometry. Next, DC were transfected with
      a plasmid encoding NY-ESO-1, a TAA expressed in numerous cancers, according to
      the transfection protocol previously established with the GFP reporter.
      Transfected DC were then co-cultured with a CD8+ NY-ESO-1 specific HLA-A*02.01 T
      cell clone to control their ability to correctly process and present the
      corresponding epitope in the HLA-A*02.01 context. Finally, T cell activation was
      assessed via flow cytometry-based detection of interferon-gamma production.
      RESULTS: An optimal KLN5/plasmid DNA ratio allowing both significant transgene
      expression and high viability of DC could be determined. Under the established
      experimental conditions, antigen processing and presentation of the
      immunodominant (SLLMWITQC(157-165)) epitope in the HLA-A*0201 context was
      demonstrated by activation of the NY-ESO-1-specific CD8+ T cell clone.
      CONCLUSIONS: KLN5-based gene transfection into DC allows the efficient induction
      of TAA presentation and may thus represent a novel attractive nonviral approach
      for cancer vaccination.

PMID- 18338822
TI  - Seven successful years of Omics research: the Human Brain Proteome Project within
      the National German Research Network (NGFN).

PMID- 18338823
TI  - An easy-to-use Decoy Database Builder software tool, implementing different decoy
      strategies for false discovery rate calculation in automated MS/MS protein
      identifications.
AB  - One of the major challenges for large scale proteomics research is the quality
      evaluation of results. Protein identification from complex biological samples or
      experimental setups is often a manual and subjective task which lacks profound
      statistical evaluation. This is not feasible for high-throughput proteomic
      experiments which result in large datasets of thousands of peptides and proteins
      and their corresponding mass spectra. To improve the quality, reliability and
      comparability of scientific results, an estimation of the rate of erroneously
      identified proteins is advisable. Moreover, scientific journals increasingly
      stipulate that articles containing considerable MS data should be subject to
      stringent statistical evaluation. We present a newly developed easy-to-use
      software tool enabling quality evaluation by generating composite target-decoy
      databases usable with all relevant protein search engines. This tool, when used
      in conjunction with relevant statistical quality criteria, enables to reliably
      determine peptides and proteins of high quality, even for nonexperienced users
      (e.g. laboratory staff, researchers without programming knowledge). Different
      strategies for building decoy databases are implemented and the resulting
      databases are characterized and compared. The quality of protein identification
      in high-throughput proteomics is usually measured by the false positive rate
      (FPR), but it is shown that the false discovery rate (FDR) delivers a more
      meaningful, robust and comparable value.

PMID- 18338824
TI  - Systematic interpretation of cyclic nucleotide binding studies using KinetXBase.
AB  - Functional proteomics aims to describe cellular protein networks in depth based
      on the quantification of molecular interactions. In order to study the
      interaction of adenosine-3',5'-cyclic monophosphate (cAMP), a general second
      messenger involved in several intracellular signalling networks, with one of its
      respective target proteins, the regulatory (R) subunit of cAMP dependent protein
      kinase (PKA), a number of different methods was employed. These include
      fluorescence polarisation (FP), isothermal titration calorimetry (ITC), surface
      plasmon resonance (SPR), amplified luminescence proximity homogeneous assay
      (ALPHA-screen), radioligand binding or activity-based assays. Kinetic,
      thermodynamic and equilibrium binding data of a variety of cAMP derivatives to
      several cAMP binding domains were integrated in a single database system, we
      called KinetXBase, allowing for very distinct data formats. KinetXBase is a
      practical data handling system for molecular interaction data of any kind,
      providing a synopsis of data derived from different technologies. This supports
      ongoing efforts in the bioinformatics community to devise formal concepts for a
      unified representation of interaction data, in order to enable their exchange and
      easy comparison. KinetXBase was applied here to analyse complex cAMP binding data
      and highly site-specific cAMP analogues could be identified. The software package
      is free for download by academic users.

PMID- 18338825
TI  - Leukemia inhibitory factor induces an antiapoptotic response in oligodendrocytes
      through Akt-phosphorylation and up-regulation of 14-3-3.
AB  - Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes (OLG)
      both in vitro and in an animal model of multiple sclerosis. Here, we show that
      LIF protects mature rat OLG cultures selectively against the combined insult of
      the proinflammatory cytokines interferon-gamma and tumor necrosis factor-alpha,
      but it does not protect against oxidative stress nor against staurosporine
      induced apoptosis. We further demonstrate that LIF activates the janus kinase
      (JAK)/signal transducer and activator of transcription 3 (STAT3) and the
      phosphatidylinositol 3 kinase/Akt pathway in mature OLG. We show that LIF
      protection is independent of suppressors of cytokine signaling and Bcl-2 mRNA
      expression levels. To gain further insight into the protective mechanism, a
      quantitative proteomic approach (DIGE) was applied to identify differentially
      expressed proteins in LIF-treated OLG. Our results indicate that LIF induces a
      shift in the cellular machinery toward a prosurvival execution program,
      illustrated by an enhanced expression of isoforms of the antiapoptotic molecule
      14-3-3. These data provide further insight into the mechanisms of LIF-mediated
      protection of mature OLGs.

PMID- 18338826
TI  - Systematic gene expression profiling of mouse model series reveals coexpressed
      genes.
AB  - A major aim of the Human Brain Proteome Project (HBPP) is a better understanding
      of the molecular etiology and progression of neurodegenerative diseases.
      Transgenic and loss-of-function mouse mutant lines (MMLs) serve as experimental
      models. Transcriptome and proteome regulate each other in a complex and
      controlled way, and their comparative analysis is an essential aspect. As a
      fundamental study, we have assessed transcript profiles using a microarray
      containing 21 000 cDNA probes in a series of disease models within the German
      Mouse Clinic (GMC). Seventeen distinct organs of one adult stage were
      systematically collected for each submitted MML. Samples for gene expression
      profiling are individually selected based on conspicuous phenotypes in at least
      one of 14 GMC phenotype screens or on previous knowledge of the mutant phenotype.
      By microarray experiments expression patterns of 90 organs from 46 MMLs were
      analysed, identifying up to 232 differentially expressed genes in 45 organs. Here
      we present an overview of the results of all MMLs analysed and demonstrate the
      efficiency of systematic genome-wide expression profiling for the detection of
      molecular phenotypes in organs of a mammalian model organism. We identify the
      recurring regulation of particular genes and groups of coexpressed genes in
      apparently unrelated MMLs.

PMID- 18338827
TI  - Proteome analysis of ventral midbrain in MPTP-treated normal and L1cam transgenic
      mice.
AB  - Treatment of mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridene hydrochloride
      (MPTP) is a well established animal model for Parkinson's disease (PD), while
      overexpression of L1 cell adhesion molecule (L1cam) has been proposed to
      attenuate the degeneration of dopaminergic neurons induced by MPTP. To gain
      insight into the role of L1cam in the pathomechanism of PD, we investigated
      protein expression patterns after MPTP-treatment in both C57BL/6 (wild-type) and
      transgenic mice overexpressing L1cam in astrocytes. Our results showed that
      during the acute phase, proteins in functional complexes responsible for
      mitochondrial, glycolysis, and cytoskeletal function were down-regulated in MPTP
      treated wild-type mice. After a recovery phase, proteins that were down-regulated
      in the acute phase reverted to normal levels. In L1cam transgenic mice, a much
      higher number of proteins was altered during the acute phase and this number even
      increased after the recovery phase. Many proteins involved in oxidative
      phosphorylation were still down-regulated and glycolysis related protein were
      still up-regulated. This pattern indicates a lasting severely impaired energy
      production in L1cam mice after MPTP treatment.

PMID- 18338828
TI  - A fusion PET-MRI system with a high-resolution research tomograph-PET and ultra
      high field 7.0 T-MRI for the molecular-genetic imaging of the brain.
AB  - We have developed a positron emission tomography (PET) and magnetic resonance
      imaging (MRI) fusion system for the molecular-genetic imaging (MGI) of the in
      vivo human brain using two high-end imaging devices: the HRRT-PET, a high
      resolution research tomograph dedicated to brain imaging on the molecular level,
      and the 7.0 T-MRI, an ultra-high field version used for morphological imaging.
      HRRT-PET delivers high-resolution molecular imaging with a resolution down to 2.5
      mm full width at half maximum (FWHM), which allows us to observe the brain's
      molecular changes using the specific reporter genes and probes. On the other
      front, the 7.0 T-MRI, with submillimeter resolution images of the cortical areas
      down to 250 mum, allows us to visualize the fine details of the brainstem areas
      as well as the many cortical and subcortical areas. The new PET-MRI fusion
      imaging system will provide many answers to the questions on neurological
      diseases as well as cognitive neurosciences. Some examples of the answers are the
      quantitative visualization of neuronal functions by clear molecular and genetic
      bases, as well as diagnoses of many neurological diseases such as Parkinson's and
      Alzheimer's. The salient point of molecular-genetic imaging and diagnosis is the
      fact that they precede the morphological manifestations, and hence, the early and
      specific diagnosis of certain diseases, such as cancers.

PMID- 18338830
TI  - Benefits of concurrent delivery of hyaluronan and IGF-1 cues to regeneration of
      crosslinked elastin matrices by adult rat vascular cells.
AB  - Elastin, a major component of vascular matrices, critically determines vascular
      mechanics and maintains the quiescence of smooth muscle cells (SMCs). Attempts to
      regenerate elastin in elastin-compromised blood vessels using tissue-engineering
      approaches is limited by the unavailability of elastogenic cues to upregulate
      poor elastin output and matrix assembly by adult vascular cells. We previously
      showed that hyaluronan (HA) elastogenically stimulates aortic SMCs, although
      these effects are highly specific to HA fragment size. The elastogenic response
      of SMCs can also be modulated with growth factors such as insulin-like growth
      factor (IGF-1). Here, we evaluate the benefits of concurrent delivery of HA
      fragments (0.76-2000 kDa) and IGF-1 (500 ng/ml) to elastin synthesis,
      organization and crosslinking. The study outcomes show that, relative to
      supplement-free cultures, IGF-1 and long-chain HA/large HA fragments, but not HA
      oligomers, together induce multifold increases in the synthesis of elastin
      precursors, structural elastin matrix yields and crosslink densities within cell
      layers, and encourage elastic fibre formation. These outcomes are not all
      obtained when either of the cues is provided separately. IGF-1 and large HA
      fragments (>20 kDa) also together inhibit cell proliferation, a concern in
      elastin-compromised vessels, where SMC hyperproliferation is common. The results
      will benefit efforts to provide exogenous or scaffold-based elastogenic cues (IGF
      1 + HMW HA/large HA fragments) to enable robust and faithful regeneration of
      elastin matrix structures in vivo or in vitro. The present outcomes may be used
      to restore elastin matrix homeostasis in de-elasticized vessels and tissue
      engineered constructs that may be grafted as a substitute.

PMID- 18338831
TI  - Downstream utrophin enhancer is required for expression of utrophin in skeletal
      muscle.
AB  - BACKGROUND: Duchenne muscular dystrophy is caused by the absence of the muscle
      cytoskeletal protein dystrophin. Utrophin is an autosomal homologue of
      dystrophin, and overexpression of utrophin is expected to compensate for the
      dystrophin deficit. We previously reported that the 5.4-kb 5'-flanking region of
      the utrophin gene containing the A-utrophin core promoter did not drive transgene
      expression in heart and skeletal muscle. To clarify the regulatory mechanism of
      utrophin expression, we generated a nuclear localization signal-tagged LacZ
      transgenic (Tg) mouse, in which the LacZ gene was driven by the 129-bp downstream
      utrophin enhancer (DUE) and the 5.4-kb 5'-flanking region of the utrophin
      promoter. METHODS: Two Tg lines were established. The levels of transgene mRNA
      expression in several tissues were examined by reverse transcriptase-polymerase
      chain reaction (RT-PCR) and quantitative RT-PCR. Cryosections of several tissues
      were stained with haematoxylin and eosin and X-gal. RESULTS: The transgene
      expression patterns were consistent with endogenous utrophin in several tissues
      including heart and skeletal muscle. Transgene expression was also up-regulated
      more in regenerating muscle than in nonregenerating muscle. Moreover, utrophin
      expression was augmented in the skeletal muscle of DUE Tg/dystrophin-deficient
      mdx mice through cross-breeding experiments. We finally established cultures of
      primary myogenic cells from this Tg mouse and found that utrophin up-regulation
      during muscle differentiation depends on the DUE motif. CONCLUSIONS: Our results
      showed that DUE is indispensable for utrophin expression in skeletal muscle and
      heart, and primary myogenic cells from this Tg mice provide a high through-put
      screening system for drugs that up-regulate utrophin expression.

PMID- 18338832
TI  - Synergistic antitumoral effects of human telomerase reverse transcriptase
      mediated dual-apoptosis-related gene vector delivered by orally attenuated
      Salmonella enterica Serovar Typhimurium in murine tumor models.
AB  - Salmonella enterica Serovar Typhimurium (S. typhimurium), a facultative anaerobe,
      has been reported to be capable of both selectively amplifying and expressing
      exogenous genes within tumors. In addition, previous studies have demonstrated
      that the human telomerase reverse transcriptase (hTERT) promoter could confine
      gene expression strictly to the telomerase-positive cancer cells. In the present
      study, we used attenuated S. typhimurium as a carrier to deliver a eukaryotic
      expression vector (pSNhTS) that contains the second mitochondria-derived
      activator of caspases (Smac) and tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL) genes under the control of the hTERT promoter. The results of in
      vitro experiments showed that Smac could enhance TRAIL-induced apoptosis in tumor
      cells and the hTERT promoter could drive specific gene expression in tumor cells,
      but not in normal cells. In vivo data in mice indicated that salmonella-mediated
      exogenous gene expression could persist for at least 14 days in tumors.
      Furthermore, S.L./SNhTS (S. typhimurium carrying the pSNhTS) was orally
      administered into mice bearing tumors, and its antitumoral effect was evaluated.
      It was observed that S.L./SNhTS significantly inhibited tumor growth by 70-90%
      and prolonged the survival of mice. This strong antitumoral activity achieved by
      S.L./SNhTS was due to the synergistic antitumoral properties of Smac and TRAIL
      recombinant proteins. Our data also support the idea that the hTERT promoter
      could be an excellent candidate for cancer-specific therapy and S. typhimurium
      appeared to be a promising strategy for the treatment of solid tumors.

PMID- 18338833
TI  - Potent antitumor effect of TRAIL mediated by a novel adeno-associated viral
      vector targeting to telomerase activity for human hepatocellular carcinoma.
AB  - BACKGROUND: Adeno-associated virus (AAV) has rapidly become a promising gene
      delivery vehicle for its excellent advantages of low pathogenicity and long-term
      gene expression. However, lack of tissue specificity caused low efficiency of AAV
      transfer to target cells. The promoter of human telomerase reverse transcriptase
      (hTERT) has been implicated in mediating gene expression in cancer cells as hTERT
      is transcriptionally upregulated in most cancer cells. Thereby, the hTERT
      promoter becomes a good candidate to enhance the targeting efficiency of AAV in
      cancer cells. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)
      functions as a soluble cytokine to selectively kill various cancer cells without
      toxicity to most normal cells. It remains to be determined whether the hTERT
      promoter can efficiently mediate TRAIL gene therapy in cancer cells using AAV
      vector. METHODS: A novel AAV vector containing the TRAIL gene under the control
      of the hTERT promoter (AAV-hTERT-TRAIL) was generated. The specific expression of
      hTERT-controlled genes was evaluated in cell lines. The antitumor efficacy of AAV
      hTERT-TRAIL was assessed in tumor cell lines and human hepatocellular carcinoma
      xenograft mouse model. RESULTS: TRAIL expression was observed in tumor cells
      infected with AAV-hTERT-TRAIL at both the protein and mRNA level. AAV-hTERT-TRAIL
      displayed cancer-specific cytotoxicity and induced tumor cell apoptosis.
      Moreover, in animal experiments, intratumoral administration of AAV-hTERT-TRAIL
      significantly suppressed the growth of xenograft tumors and resulted in tumor
      cell death. CONCLUSIONS: AAVs in combination with hTERT-mediated therapeutic gene
      expression provide a promising targeting approach for developing effective
      therapy for human cancers. These data suggest that AAV-hTERT-TRAIL is a potent
      therapeutic agent for cancer therapy.

PMID- 18338834
TI  - Neoadjuvant gene delivery of feline granulocyte-macrophage colony-stimulating
      factor using magnetofection for the treatment of feline fibrosarcomas: a phase I
      trial.
AB  - Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have
      high recurrence rates. Immunostimulatory gene therapy is a promising approach in
      veterinary oncology. This phase I dose-escalation study was performed to
      determine toxicity and feasibility of gene therapy with feline granulocyte
      macrophage colony-stimulating factor (feGM-CSF) in cats with fibrosarcomas.
      Twenty cats were treated with plasmid coding for feGM-CSF attached to magnetic
      nanoparticles in doses of 50, 250, 750 and 1250 microg. Two preoperative
      intratumoral injections followed by magnetofection were given. Four control cats
      received only surgical treatment. Adverse events were recorded and correlated
      according to the veterinary co-operative oncology group toxicity scale. An enzyme
      linked immunosorbent assay was performed to detect plasma feGM-CSF
      concentrations. No significant treatment related toxicity was observed.
      Preliminary recurrence results were encouraging as, on day 360, ten of 20 treated
      cats were recurrence-free. In conclusion, 1250 microg of feGM-CSF plasmid DNA
      applied by magnetofection is safe and feasible for phase II testing.

PMID- 18338835
TI  - The cyclo-oxygenase 2 promoter is induced in nontarget cells following adenovirus
      infection, but an AU-rich 3'-untranslated region destabilization element can
      increase specificity.
AB  - BACKGROUND: Cyclo-oxygenase 2 (Cox-2) is expressed in many types of tumors, but
      typically undetectable in normal tissues. However, Cox-2 is known to be induced
      following infection by many microbial agents, which might threaten the tumor
      selectivity of the Cox-2 promoter in the context of virotherapy or viral gene
      delivery. Cox-2 expression is regulated in part post-transcriptionally by
      stimulation or inhibition of mRNA degradation by 3'-untranslated region (3'-UTR)
      AU-rich elements. In the present study, we investigated the induction of the Cox
      2 promoter both in normal and tumor cells after adenovirus infection and explored
      the utility of AU-rich elements for regaining promoter selectivity. METHODS:
      Nontumor and tumor cells were transfected in vitro and in vivo with plasmids
      containing the Cox-2 or cytomegalovirus immediate early promoter driving
      luciferase (with or without 3'-UTR elements) followed by adenoviral infection.
      Selectivity and activity of the promoters and 3'-UTR elements were analysed by
      luciferase assay and in-vivo imaging. RESULTS: The Cox-2 promoter was induced in
      both normal and tumor cells following infection with E1 containing replicative
      adenoviruses but not in the absence of E1. Utilization of AU-rich elements
      counteracted promoter induction in vitro and in vivo in nonmalignant cells but
      not in cancer cells, thus increasing the selectivity of the approach ten-fold
      without loss of potency. CONCLUSIONS: Adenoviral infection induces the Cox-2
      promoter in normal and tumor cells, which might compromise specificity of the
      promoter. Utilization of AU-rich destabilization elements can rescue the tumor
      selectivity of the promoter.

PMID- 18338836
TI  - Adeno-associated virus-mediated expression of kallistatin suppresses local and
      remote hepatocellular carcinomas.
AB  - BACKGROUND: The current treatments for hepatocellular carcinoma (HCC) are poor,
      particularly for metastatic HCC. Intraportal transfusion of adeno-associated
      virus (AAV) leads to long-term and persistent transgenic expression in livers.
      Kallistatin, a novel angiogenesis inhibitor, exhibits anti-tumor activity. The
      aim of the study was to investigate whether intraportal injection of AAV
      kallistatin could suppress local and metastatic HCC in mice. METHODS: An AAV
      vector encoding kallistatin was constructed, and its transduction efficiency by
      intraportal transfusion in livers was examined by RT-PCR, immunohistochemical and
      Western blotting analysis. The anti-tumor activity was tested in three HCC models
      including hepatic and subcutaneous human Hep3B HCC tumors in BALB/c athymic
      (nu/nu) mice, and subcutaneous mouse BNL HCC tumors in BALB/c mice. Tumor cell
      proliferation in situ was examined by anti-Ki-67 staining, and apoptosis by
      TUNEL. RESULTS: Gene transfection by rAAV-kallistatin inhibited proliferation of
      human umbilical vein endothelial cells and HCC cells in vitro. Intraportal
      injection of rAAV-kallistatin resulted in persistent and specific expression of
      kallistatin in livers detected by RT-PCR and immunohistochemical analysis, and
      kallistatin protein in circulation detected by Western blotting analysis.
      Intraportal injection of rAAV-kallistatin significantly suppressed angiogenesis
      and growth of hepatic Hep3B tumors. The kallistatin released by hepatocytes into
      the circulation suppressed remote Hep3B and BNL tumors established
      subcutaneously. The rAAV-kallistatin gene therapy significantly inhibited tumor
      cell proliferation and induced apoptosis. CONCLUSIONS: Intraportal injection of
      rAAV-kallistatin suppressed hepatic and subcutaneous HCC tumors, relying on its
      anti-angiogenic and anti-proliferative activities.

PMID- 18338837
TI  - Relationship between coracoacromial arch and rotator cuff analysed by a computer
      assisted method.
AB  - BACKGROUND: In this paper we describe and assess the feasibility of a computer
      assisted method which could be useful to investigate the mechanism of subacromial
      impingment of the shoulder. METHODS: The relationship between the infraspinatus
      and supraspinatus and the coracoacromial (CA) arch during passive elevation and
      abduction are described. The methodology is based on the use of a tracker for
      recording surfaces and passive movements and data elaboration using dedicated
      software. RESULTS: In four cadavers, we observed that the minimal distances
      between the rotator cuff insertions and CA arch were realized at 45 degrees
      abduction between the acromion and infraspinatus, at 50-90 degrees elevation
      between the acromion and supraspinatus and also at 45-70 degrees abduction
      between the CA ligament and supraspinatus. This study showed that the proposed
      method is able to provide repeatable kinematic data (ICC > or = 0.90), numerical
      anatomical data comparable with the literature and, moreover, individual
      measurements on the shoulder joint. CONCLUSIONS: This preliminary results support
      the extension of the methodology to an in vivo protocol to be used during
      computer-assisted arthroscopic surgery.

PMID- 18338838
TI  - In vivo evaluation of human dental pulp stem cells differentiated towards
      multiple lineages.
AB  - An increasing number of investigations supports that adult stem cells have the
      potential to differentiate into matured cell types beyond their origin, a
      property defined as plasticity. Previously, the plasticity of stem cells derived
      from dental pulp (DPSC) has been confirmed by culturing cells in lineage-specific
      media in vitro. In the current study, the in vivo differentiation or maturation
      potential of DPSC was further analysed, by transplanting human DPSC/collagen
      scaffold constructs into subcutaneous tissue of immunocompromised mice. Cells
      received odontogenic, adipogenic or myogenic pre-induction, whereas control
      samples received no stimulation. Also blank collagen scaffolds were implanted.
      The results indicated that seeded cells produced tissue within the implanted
      constructs after 3 weeks of implantation. According to morphological and
      phenotypical changes, the pre-induced DPSC showed the ability to further
      differentiate along odontogenic, myogenic and adipogenic pathways in vivo.
      Moreover, DPSC without pre-treatment were able to spontaneously differentiate
      along odontogenic and adipogenic directions in vivo. However, only limited mature
      morphological changes were detected in histology. In summary, stem cells derived
      from human dental pulp form a suitable source for tissue engineering and cell
      mediated therapy, although additional analyses should be considered.

PMID- 18338839
TI  - A dimerizable cationic lipid with potential for gene delivery.
AB  - BACKGROUND: Despite the use of currently optimized lipofection conditions,
      including transfection in serum-depleted media, the efficiency of gene transfer
      is low and high transfection rates often induce cytotoxicity. A lipid formulation
      with transfection efficiency not inhibited by serum would provide an advance
      towards in vivo applications. METHODS: We explored the ability of the cationic
      lipid SH-14 to dimerize upon DNA and form lipoplexes, and potentially release
      nucleic acids in the intracellular reducing milieu. We investigated the critical
      micelle-forming concentration of SH-14 and its intrinsic toxicity, size and Zeta
      potential measurements, the in vitro cytotoxicity of SH-14/plasmid DNA lipoplexes
      and their ability to transfect cells. RESULTS: Among all the charge ratios (CR, +
      /-) tested, lipoplexes at CR 10 with a mean diameter of 295 nm and a surface
      charge of + 20 mV, exhibited the best compromise between transfection efficiency
      and tolerability. SH-14 presented the same cytotoxicity level whether alone or
      complexed in lipoplexes. Lipofections carried out in serum-free medium shared a
      transfection efficiency, on average, of 40% and a cytotoxicity of 38%. An
      increase of 73% in transfection efficiency and 24% in cell viability were
      obtained, extending lipofection over 48 h in complete-medium. Moreover, when
      serum concentration was increased from 10% to 50%, a three-fold increase in
      plasmid dose led to more than 72% of cells being transfected with almost no sign
      of cytotoxicity. CONCLUSIONS: Overall, SH-14 presents good potential as a novel
      transfection reagent to be used in the presence of serum.

PMID- 18338840
TI  - Synthesis and characterization of core-shell star copolymers for in vivo PET
      imaging applications.
AB  - The synthesis of core-shell star copolymers via living free radical
      polymerization provides a convenient route to three-dimensional nanostructures
      having a poly(ethylene glycol) outer shell, a hydrophilic inner shell bearing
      reactive functional groups, and a central hydrophobic core. By starting with well
      defined linear diblock copolymers, the thickness of each layer, overall
      size/molecular weight, and the number of internal reactive functional groups can
      be controlled accurately, permitting detailed structure/performance information
      to be obtained. Functionalization of these polymeric nanoparticles with a DOTA
      ligand capable of chelating radioactive (64)Cu nuclei enabled the biodistribution
      and in vivo positron emission tomography (PET) imaging of these materials to be
      studied and correlated directly to the initial structure. Results indicate that
      nanoparticles with increasing PEG shell thickness show increased blood
      circulation and low accumulation in excretory organs, suggesting application as
      in vivo carriers for imaging, targeting, and therapeutic groups.

PMID- 18338841
TI  - Linezolid (ZYVOX), the first member of a completely new class of antibacterial
      agents for treatment of serious gram-positive infections.

PMID- 18338842
TI  - Amide-based prodrugs of spermidine-bridged dinuclear platinum. Synthesis, DNA
      binding, and biological activity.
AB  - The chemistry and biology of acetyl-protected spermidine-bridged dinuclear
      platinum complexes [{ trans-PtCl(NH 3) 2] 2-mu-NH 2(CH 2) 3N(COR)(CH 2) 4NH 2]X 2
      (R = H, X = Cl (1,1/t,t-spermidine, BBR3571); R = CH 3 , X = Cl ( 2); R = CH 2
      Cl, X = ClO 4 ( 3); R = CF 3 , X = Cl ( 4)) are compared with their carbamate
      analogues. The compounds are potential prodrugs for the parent compound 1, a
      highly potent antitumor agent. At pH 6-8 hydrolysis of the blocking group with
      the release of the "parent" protonated species follows the order 4 > 3 >> 2. For
      4, rate constants for the deprotection increase in this pH range. The DNA binding
      profile of 4 is similar to the Boc derivative, confirming the central influence
      of charge on DNA binding properties. The differences in cytotoxicity for the
      protected compounds in ovarian carcinoma cell lines sensitive and resistant to
      cisplatin cannot completely be explained by spontaneous release of 1,1/t,t
      spermidine at physiological pH. Inherent cytotoxicity and cell line specificity
      may contribute to the observed behavior. The properties of the compounds present
      them also as possible "second-generation" analogues of the clinically relevant
      trinuclear complex [{ trans-PtCl(NH 3) 2} 2-mu- trans-Pt(NH 3) 2(NH 2(CH 2) 6NH
      2) 2](NO 3) 4, ( 8, BBR3464).

PMID- 18338843
TI  - Synthesis and pharmacological characterization at glutamate receptors of the four
      enantiopure isomers of tricholomic acid.
AB  - The two enantiomeric pairs of erythro- and threo-amino-(3'-hydroxy-4',5'-dihydro
      isoxazol-5'-yl)-acetic acids were synthesized via the 1,3-dipolar cycloaddition
      of bromonitrile oxide to ( R)- or ( S)-3-( tert-butoxycarbonyl)-2,2-dimethyl-4
      vinyloxazolidine. The pharmacological profiles of the studied amino acids reflect
      the relationship between the activity/selectivity and the stereochemistry of the
      two stereogenic centers: while the (2 S,5' S) stereoisomer is an agonist at the
      AMPA and KA receptors, its (2 R,5' R) enantiomer interacts selectively with the
      NMDA receptors; the (2 S,5' R) stereoisomer is the only one capable to activate
      the mGluRs.

PMID- 18338844
TI  - Enhancement of ordinal CoMFA by ridge logistic partial least squares.
AB  - Conventional comparative molecular field analysis (CoMFA) requires at least 3
      orders of experimental data, such as IC 50 and K i, to obtain a good model,
      although practically there are many screening assays where biological activity is
      measured only by rating scale. To improve three-dimensional quantitative
      structure-activity relationship (3D-QSAR) analysis, we developed in this study a
      modified ordinal classification-oriented CoMFA using partial-least-squares
      generalized linear regression and ridge estimation. The modified Logistic CoMFA
      was validated using a corticosteroid binding globulin receptor binding data set,
      a benchmark for 3D-QSAR, and an acetylcholine esterase inhibitor data set. Our
      results show that modification of Logistic CoMFA enhanced both prediction
      accuracy and 3D graphical analysis. In addition, the 3D graphical analysis of the
      modified Logistic CoMFA was much improved. This improvement resulted in more
      accurate information on the binding mode between proteins and ligands than in the
      case of conventional CoMFA.

PMID- 18338845
TI  - Hydra: a self regenerating high performance computing grid for drug discovery.
AB  - Computer aided drug design is progressing and playing an increasingly important
      role in drug discovery. Computational methods are being used to evaluate larger
      and larger numbers of real and virtual compounds. New methods based on molecular
      simulations that take protein and ligand flexibility into account also contribute
      to an ever increasing need for compute time. Computational grids are therefore
      becoming a critically important tool for modern drug discovery, but can be
      expensive to deploy and maintain. Here, we describe the low cost implementation
      of a 165 node, computational grid at Anadys Pharmaceuticals. The grid makes use
      of the excess computing capacity of desktop computers deployed throughout the
      company and of outdated desktop computers which populate a central computing
      grid. The performance of the grid grows automatically with the size of the
      company and with advances in computer technology. To ensure the uniformity of the
      nodes in the grid, all computers are running the Linux operating system. The
      desktop computers run Linux inside MS Windows using coLinux as virtualization
      software. HYDRA has been used to optimize computational models, for virtual
      screening and for lead optimization.

PMID- 18338846
TI  - Unusual structural types in polynuclear iron chemistry from the use of N,N,N',N'
      tetrakis(2-hydroxyethyl)ethylenediamine (edteH4): Fe5, Fe6, and Fe12 clusters.
AB  - The syntheses, crystal structures, and magnetochemical characterization of five
      new iron clusters [Fe5O2(O2CPh)7(edte)(H2O)] (1), [Fe6O2(O2CBut)8(edteH)2] (2),
      [Fe12O4(OH)2(O2CMe)6(edte)4(H2O)2](ClO4)4 (3), [Fe12O4(OH)8(edte)4(H2O)2](ClO4)4
      (4), and [Fe12O4(OH)8(edte)4(H2O)2](NO3)4 (5) (edteH4= N,N,N',N'-tetrakis(2
      hydroxyethyl) ethylenediamine) are reported. The reaction of edteH4 with
      [Fe3O(O2CPh)6(H2O)3](NO3) and [Fe3O(O2CBut)6(H2O)3](OH) gave 1 and 2,
      respectively. Complex 3 was obtained from the reaction of edteH4 and NaO2CMe with
      Fe(ClO4)3, whereas 4 and 5 were obtained from the reaction of edteH4 with
      Fe(ClO4)3 and Fe(NO3)3, respectively. The core of 1 consists of a [Fe4(mu3-O)2]8+
      butterfly unit to which is attached a fifth Fe atom by four bridging O atoms. The
      core of 2 consists of two triangular [Fe3(mu3-O)]7+ units linked together by six
      bridging O atoms. Finally, the cores of 3-5 consist of an [Fe12(mu4-O)4(mu
      OH)2]26+ unit. Variable-temperature (T) and -field (H) solid-state direct and
      alternating current magnetization (M) studies were carried out on complexes 1-3
      in the 1.8-300 K range. Analysis of the obtained data revealed that 1, 2, and 3-5
      possess an S = 5/2, 5, and 0 ground-state spin, respectively. The fitting of the
      obtained M/N(muB) vs H/T data was carried out by matrix diagonalization, and this
      gave values for the axial zero-field splitting (ZFS) parameter D of -0.50 cm-1
      for 1 and -0.28 cm-1 for 2.

PMID- 18338847
TI  - Palladium nanoparticles stabilized by an ionic polymer and ionic liquid: a
      versatile system for C-C cross-coupling reactions.
AB  - Highly stable palladium nanoparticles (Pd NPs), protected by an imidazolium-based
      ionic polymer (IP) in a functionalized ionic liquid (IL), have been prepared and
      characterized by transmission electron microscopy (TEM). These Pd NPs are
      excellent precatalysts for Suzuki, Heck, and Stille coupling reactions and can be
      stored without undergoing degradation for at least 2 years. The NP-IP-IL system
      may therefore be considered as an alternative to the traditional palladium on
      carbon (Pd/C) precatalyst employed in many C-C coupling reactions, also allowing
      reactions to be conducted under "solvent-free" conditions.

PMID- 18338848
TI  - Versatile approach toward the self-assembly of heteromultimetallic salen
      structures.
AB  - A general route is presented toward the template-directed preparation of self
      assembled heteromultimetallic salen structures using noncovalent coordinative
      metal-ligand interactions. Various higher order assemblies have been studied in
      detail using a combination of NMR spectroscopy and X-ray crystallography.

PMID- 18338849
TI  - Preparations and photophysical properties of fused and nonfused thienyl bridged
      MM (M = Mo or W) quadruply bonded complexes.
AB  - A series of metal-metal quadruply bonded compounds [(tBuCO2)3M2]2(mu-TT) where TT
      = thienothiophenedicarboxylate and M = Mo, 1A, and M = W, 1B and
      [(tBuCO2)3M2]2(mu-DTT) where DTT = dithienothiophenedicarboxylate and M = Mo, 2A,
      and M = W, 2B, has been prepared and characterized by elemental analysis, ESI-
      and MALDI-TOF mass spectrometry and 1H NMR spectroscopy. Their photophysical
      properties have also been investigated by steady-state absorption as well as
      transient absorption and emission spectroscopy. The optimized structures and the
      predicted low energy electronic transitions were obtained by DFT and time
      dependent DFT calculations, respectively, on model compounds. These results, in
      combination with the respective properties of the compounds [(tBuCO2)3M2]2(mu
      BTh) (BTh = 2,5'-bithienyldicarboxylate, M = Mo, 3A, and M = W, 3B), allow us to
      make a comprehensive comparison of the fused (compounds 1A, 1B, 2A, and 2B) and
      the nonfused thienyl (compounds 3A and 3B) dicarboxylate bridged compounds of
      molybdenum and tungsten. The electrochemical studies show singly oxidized radical
      cations that are valence trapped on the EPR time-scale and are classified as
      Class 1 (M = Mo) or Class 2 (M = W) on the Robin and Day scale for mixed valence
      compounds. The new compounds exhibit intense metal to bridge ligand charge
      transfer absorption bands in the far visible and near IR (NIR) region. Both
      molybdenum and tungsten complexes show dual emission, but for molybdenum, the
      phosphorescence is dominant while for tungsten the emission is primarily
      fluorescence. Femtosecond transient absorption spectroscopy shows that the
      relaxation dynamics of the S1 states which have lifetimes of approximately 10 ps
      is dominated by intersystem crossing (ISC), leading to T1 states that in turn
      possess long lifetimes, approximately 70 micros (M = Mo) or 3 micros (M = W).
      These properties are contrasted with the photophysical properties of conjugated
      organic systems incorporating metal ions of the later transition elements.

PMID- 18338850
TI  - Crystal structures and thermal and electrical properties of the new silver
      (poly)chalcogenide halides Ag23Te12Cl and Ag23Te12Br.
AB  - Two new silver (poly)chalcogenide halides, Ag23Te12Cl and Ag23Te12Br, were
      characterized by powder X-ray phase analysis, energy dispersive X-ray analysis,
      and crystal structure determinations at various temperatures. Thermal analyses of
      both compounds and electrochemical measurements for the bromide completed the
      investigation. The compounds Ag23Te12X (X = Cl, Br) are isostructural and
      crystallize orthorhombically (space group Pnnm, Z = 4) as systematic twins. The
      lattice parameter values derived from X-ray powder data were a = 21.214(2) A, b =
      21.218(2) A, c = 7.7086(7) A, and V = 3469.8(6) A (3) for Ag23Te12Cl at 293 K and
      a = 21.170(1) A, b = 21.170(1) A, c = 7.7458(5) A, and V = 3471.4(4) A (3) for
      Ag23Te12Br at 298 K. An enhanced silver ion mobility was revealed by impedance
      spectroscopy investigations. No phase transitions were observed in the
      temperature range 100-750 K. These two silver(I) (poly)chalcogenide halides are
      the second set of representatives of a new class of coinage-metal
      (poly)chalcogenide halides in which both covalently bonded [Te2](2-) dumbbells
      and ionically bonded Te(2-) anions appear.

PMID- 18338851
TI  - Diruthenium(II,III) bis(tetramethyl-1,3-benzenedipropionate) as a novel catalyst
      for tert-butyl hydroperoxide oxygenation.
AB  - The reaction of Ru2(OAc)4Cl with 2.2 equiv of H2esp (esp =
      alpha,alpha,alpha',alpha'-tetramethyl-1,3-benzenedipropionate) resulted in a new
      compound, Ru2(esp)2Cl (1), that is soluble in organic media. 1 is an active
      catalyst for the oxygenation of organic sulfides by tert-butyl hydroperoxide
      (TBHP) in both an acetonitrile solution or neat (solvent-free) conditions.
      Solvent-free reactions display the quantitative utility of TBHP and hence
      excellent chemical selectivity for sulfoxide formation.

PMID- 18338852
TI  - Ribosomal synthesis of peptidase-resistant peptides closed by a nonreducible
      inter-side-chain bond.
AB  - Here we report a new enabling technology for the synthesis of peptidase-resistant
      cyclic peptides by means of genetic code reprogramming involving the flexizyme (a
      tRNA acylation ribozyme) and PURE (a reconstituted cell-free translation)
      systems. In this work, we have developed a new nonproteinogenic amino acid
      bearing a chloroacetyl group in the side chain, which forms a physiologically
      stable thioether bond by intramolecular reaction with the sulfhydryl group of a
      Cys residue in the peptide chain upon translation. Significantly, this chemistry
      takes place spontaneously in situ of the translation solution, giving the
      corresponding cyclic peptides independent of ring sizes. We have used this method
      to convert human urotensin II, known as a potent vasoconstrictor, to its analogue
      containing a thioether bond, showing that this new analogue retains biological
      activity. Moreover, this peptide exhibits remarkable resistance against
      peptidases under reducing conditions. Thus, this technology offers a new means to
      accelerate the discovery of therapeutic peptidic drugs.

PMID- 18338853
TI  - Regioisomeric SCFA attachment to hexosamines separates metabolic flux from
      cytotoxicity and MUC1 suppression.
AB  - Chemical biology studies, exemplified by metabolic glycoengineering experiments
      that employ short chain fatty acid (SCFA)-hexosamine monosaccharide hybrid
      molecules, often suffer from off-target effects. Here we demonstrate that
      systematic structure-activity relationship (SAR) studies can deconvolute multiple
      biological activities of SCFA-hexosamine analogues by demonstrating that
      triacylated monosaccharides, including both n-butyrate- and acetate-modified
      ManNAc analogues, had dramatically different activities depending on whether the
      free hydroxyl group was at the C1 or C6 position. The C1-OH (hemiacetal)
      analogues enhanced growth inhibition in MDA-MB-231 human breast cancer cells and
      suppressed expression of MUC1, which are attractive properties for an anticancer
      agent. By contrast, C6-OH analogues supported high metabolic flux into the sialic
      acid pathway with negligible growth inhibition or toxicity, which are desirable
      properties for glycan labeling in healthy cells. Importantly, these SAR were
      general, applying to other hexosamines ( e.g., GlcNAc) and non-natural sugar
      "scaffolds" ( e.g., ManNLev). From a practical standpoint, the ability to
      separate toxicity from flux will facilitate the use of MOE analogues for cancer
      treatment and glycomics applications, respectively. Mechanistically, these
      findings overturn the premise that the bioactivities of SCFA-monosaccharide
      hybrid molecules result from their hydrolysis products ( e.g., n-butyrate, which
      acts as a histone deacetylase inhibitor, and ManNAc, which activates sialic acid
      biosynthesis); instead the SAR establish that inherent properties of partially
      acylated hexosamines supersede the cellular responses supported by either the
      acyl or monosaccharide moieties.

PMID- 18338854
TI  - Ex vivo analysis of synergistic anion binding to FbpA in Gram-negative bacteria.
AB  - Ferric binding protein, FbpA, is a member of the transferrin superfamily whose
      function is to move an essential nutrient, iron, across the periplasm and into
      the cytosol through formation of a ternary complex containing Fe (3+) and a
      synergistic anion, X. Here we utilize SUPREX ( stability of unpurified proteins
      from rates of H/D exchange) to determine the identification and distribution of
      the synergistic anion in FeFbpA-X species in periplasmic preparations from Gram
      negative bacteria. SUPREX is a mass spectrometry-based technique uniquely suited
      for thermodynamic analyses of protein-ligand complexes in complex biological
      mixtures such as periplasmic preparations. Model binary mixtures of FeFbpA-Cit
      and FeFbpA-PO 4 were initially characterized by SUPREX due to the likely presence
      of citrate and phosphate ions in the periplasm. Ex vivo SUPREX analyses were
      performed on FeFbpA-X species overexpressed in an Escherichia coli cell line and
      on endogenous FeFbpA-X species in Neisseria gonorrheae. Detected in the E. coli
      periplasmic extract were two distinct populations of FbpA, including one in which
      the protein was unliganded (i.e., apoFbpA) and one in which the protein was bound
      to iron and the synergistic anion, phosphate (i.e., FeFbpA-PO 4). FeFbpA-PO 4 was
      the only population of FbpA molecules detected in the N. gonorrheae periplasmic
      extract. This work provides the first determination of the identity of the in
      vivo anion bound to FeFbpA-X in the periplasm and substantiates the hypothesis
      that the synergistic anion plays a structural and functional role in FbpA
      mediated transport of iron across the periplasm and into the cytosol.

PMID- 18338855
TI  - Modeling the active-site structure of the cbb3-type oxidase from Rhodobacter
      sphaeroides.
AB  - The active site of the heme-copper oxidases comprises a redox-active high-spin
      heme and a tris-histidine copper center Cu B. Two amino acids in the close
      vicinity of the metals, a tyrosine and a tryptophan from helix 6, have been shown
      to be absolutely required for the catalytic function and should be considered
      part of the active site. Additionally, amino acid residues from interhelical
      loops strongly modify the activity. In a separate subfamily of heme-copper
      oxidases, the cbb 3-type oxidases, the metal centers are identical, the tyrosine
      is found in helix 7, but nothing is known of the corresponding tryptophan or of
      the involvement of the loop residues. We have observed a conserved aromatic
      cluster in the known oxidase structures, including the essential tryptophan and
      loop residues, and refined our earlier model of the cbb 3-type oxidase from
      Rhodobacter sphaeroides to test the feasibility of a similar structure. In the
      refined model, the interactions around the Delta-propionate of the high-spin heme
      resemble closely those seen in crystal structures of other terminal oxidases. Two
      alternative models (G- and C-models) that differ for the positioning of conserved
      tryptophans in helix 6, are presented. Molecular dynamics simulations on the
      catalytic subunit of the cbb 3-type oxidase model result in a conformational
      change of the active-site tyrosine, which may be related to different ligand
      binding properties of the cbb 3-type oxidases. The relationship between sequence
      and functional data for defining the subfamily is discussed.

PMID- 18338856
TI  - Interdomain fluorescence resonance energy transfer in SERCA probed by cyan
      fluorescent protein fused to the actuator domain.
AB  - We have used a biosynthetically incorporated fluorescent probe to monitor domain
      movements involved in ion transport by the sarcoendoplasmic reticulum Ca-ATPase
      (SERCA) from rabbit fast-twitch skeletal muscle. X-ray crystal structures suggest
      that the nucleotide-binding (N) and actuator (A) domains of SERCA move apart by
      several nanometers upon Ca binding. To test this hypothesis, cDNA constructs were
      created to fuse cyan-fluorescent protein (CFP) to the N terminus of SERCA (A
      domain). This CFP-SERCA fluorescent fusion protein retained activity when
      expressed in Sf21 insect cells using the baculovirus system. Fluorescence
      resonance energy transfer (FRET) was used to monitor the A-N interdomain distance
      for CFP-SERCA selectively labeled with fluorescein isothiocyanate (FITC) at Lys
      515 in the N domain. At low [Ca (2+)] (E2 biochemical state), the measured FRET
      efficiency between CFP (donor in A domain) and FITC (acceptor in N domain) was
      0.34 +/- 0.03, indicating a mean distance of 61.6 +/- 2.0 A between probes on the
      two domains. An increase of [Ca (2+)] to 0.1 mM (E1-Ca biochemical state)
      decreased the FRET efficiency by 0.06 +/- 0.03, indicating an increase in the
      mean distance by 3.0 +/- 1.2 A. Quantitative molecular modeling of dual-labeled
      SERCA, including an accurate calculation of the orientation factor, shows that
      the FRET data observed in the absence of Ca is consistent with the E2 crystal
      structure, but the increase in distance (decrease in FRET) induced by Ca is much
      less than predicted by the E1 crystal structure. We conclude that the E1 crystal
      structure does not reflect the predominant structure of SERCA under physiological
      conditions in a functional membrane bilayer.

PMID- 18338857
TI  - Efficient synthesis of gamma-lactams by a tandem reductive
      amination/lactamization sequence.
AB  - A three-component method for the synthesis of highly substituted gamma-lactams
      from readily available maleimides, aldehydes, and amines is described. A new
      reductive amination/intramolecular lactamization sequence provides a
      straightforward route to the lactam products in a single manipulation. The
      general utility of this method is demonstrated by the parallel synthesis of a
      gamma-lactam library.

PMID- 18338858
TI  - Preparation of Rh[16aneS4-diol](211)At and Ir[16aneS4-diol](211)At complexes as
      potential precursors for astatine radiopharmaceuticals. Part I: Synthesis.
AB  - The goal of this study was to evaluate a new approach that can be applied for
      labeling biomolecules with (211)At. Many astatine compounds that have been
      synthesized are unstable in vivo, providing motivation for seeking different
      (211)At labeling strategies. The approach evaluated in this study was to attach
      astatide anions to soft metal cations, which are also complexed by a bifunctional
      ligand. Ultimately, this complex could in principle be subsequently conjugated to
      a biomolecule with the proper selection of ligand functionality. We report here
      the attachment of (211)At(-) and *I(-) (*I = (131)I or (125)I) anions to the soft
      metal cations Rh(III) and Ir(III), which are complexed by the 1,5,9,13
      tetrathiacyclohexadecane-3,11-diol (16aneS4-diol) ligand. Radioactive *I(-)
      anions were used for preliminary studies directed at the optimization of reaction
      conditions and to provide a baseline for comparison of results with (211)At. Four
      complexes Rh[16aneS4-diol]*I/(211)At and Ir[16aneS4-diol]*I/(211)At were
      synthesized in high yield in a one-step procedure, and the products were
      characterized mainly by paper electrophoresis and reversed-phase HPLC. The
      influences of time and temperature of heating and concentrations of metal cations
      and sulfur ligand 16aneS4-diol, as well as pH on the reaction yields were
      determined. Yields of about 80% were obtained when the quantities of Rh(III) or
      Ir(III) cations and 16aneS4-diol ligand in the solutions were 62.5 nmol and 250
      nmol, respectively, and the pH ranged 3.0-4.0. Syntheses required heating for 1
      1.5 h at 75-80 degrees C. The influence of microwave heating on the time and
      completeness of the complexation reaction was evaluated and compared with the
      conventional method of heating in an oil bath. Microwave synthesis accelerates
      reactions significantly. With microwave heating, yields of about 75% for
      Rh[16aneS4-diol](131)I and Ir[16aneS4-diol](131)I complexes were obtained after
      only 20 min exposure of the reaction mixtures to microwave radiation. In
      conclusion, this study has shown that it is possible to attach an astatide anion
      to soft metal cations in a simple and fast one-step procedure, with high yields.
      These complexes will be evaluated as reagents for labeling biomolecules.

PMID- 18338859
TI  - Pores formation on cell membranes by hederacolchiside A1 leads to a rapid release
      of proteins for cytosolic subproteome analysis.
AB  - Hederacolchiside A1 was used to progressively permeabilize the membrane of human
      melanoma MEL-5 cells. Holes formation was followed by Scanning Electron
      Microscopy and interaction of the saponin with cholesterol and phospholipids by
      TOF-SIMS. 2D-LC-MS/MS and 2D-SDS-PAGE show that the release of soluble proteins
      into serum-free culture media increases with time. This can lead to a new rapid
      and efficient strategy to analyze the cytosolic subproteome and it opens the door
      to get information from the cytosolic compartment for clinical proteomic studies.

PMID- 18338860
TI  - Proteomics analysis of rice lesion mimic mutant (spl1) reveals tightly localized
      probenazole-induced protein (PBZ1) in cells undergoing programmed cell death.
AB  - Numerous reports have predicted/hypothesized a role for probenazole-induced
      protein (PBZ1) as a molecular marker in rice self-defense mechanism. However, the
      precise function of PBZ1 remains unknown. In the present study, we examined PBZ1
      as a putative cell death marker in rice. For this, we focused our attention on a
      rice lesion mimic mutant (LMM), spotted leaf 1 ( spl1), which has been used to
      study the programmed cell death (PCD) phenomenon during lesion development in
      leaf. Using two-dimensional gel electrophoresis (2-DGE), 18 colloidal Coomassie
      brilliant blue stained protein spots were found to be differentially expressed in
      the leaves of spl1 mutant. After analysis of these spots by MALDI-TOF-MS, we
      identified the PBZ1 protein to be highly inducible in spl1. On the basis of these
      results, we proceeded to verify whether PBZ1 is highly expressed in the tissues
      undergoing PCD in rice. To do so, we performed immunoblot analysis and
      immunolocalization and used transgenic lines carrying the PBZ1 promoter fused
      with GFP. Results demonstrated that the expression levels and localizations of
      PBZ1 dramatically coincided with tissues undergoing PCD, namely, during leaf
      senescence, root aerenchyma formation, coleoptiles senescence, root cap, and seed
      aleurone layer. Furthermore, localization of the PBZ1 protein was also tightly
      correlated with TUNEL signal in the seed aleurone layer. As DNA fragmentation is
      a hallmark of PCD, this result clearly indicates a role for PBZ1 in rice tissues
      undergoing PCD. In conclusion, our results provide strong support for the
      hypothesis that PBZ1 is a molecular marker in rice defense response, and can
      serve as a novel potential marker for cell death/PCD in rice.

PMID- 18338862
TI  - First evidence of a functional interaction between DNA quadruplexes and poly(ADP
      ribose) polymerase-1.
AB  - We discovered that the abundant human nuclear protein poly(ADP-ribose) polymerase
      1 (hPARP-1) binds to intramolecular DNA quadruplexes in vitro with high affinity
      and with a stoichiometry of two proteins for one quadruplex. Using an enzymatic
      assay, we have shown that hPARP-1 gets catalytically activated upon binding to G
      quadruplexes localized at the c-kit promoter and human telomere regions. This is
      the first example of a truly functional quadruplex-protein interaction, which has
      possible implications in understanding hPARP-1 mediated mechanisms of
      transcription regulation and telomere end protection.

PMID- 18338863
TI  - pH memory of immobilized lipase for (+/-)-menthol resolution in ionic liquid.
AB  - Magnetic DEAE-GMA-EDMA microspheres were prepared via suspension polymerization
      and used for the immobilization of Candida rugosa lipase by ion exchange. The
      effect of pH values on the immobilization of lipase was investigated. Resolution
      of (+/-)-menthol in the hydrophobic ionic liquid 1-butyl-3-methylimidazolium
      hexafluorophosphate was performed by immobilized lipase-catalyzed
      enantioselective esterification with propionic anhydride as acyl donor. The
      effects of pH condition at lipase immobilization on the conversion and
      enantioselectivity were investigated. As a result, pH memory of the immobilized
      lipase for catalyzing (+/-)-menthol resolution in the ionic liquid was observed.
      Better conversion and the best enantioselectivity were obtained with the
      immobilized lipase prepared at pH 5.0. Under the condition, (-)-menthyl
      propionate with enantiomeric excess of >90% was obtained. Moreover, the
      enantioselectivity of the immobilized lipase decreased gradually with increasing
      pH value.

PMID- 18338864
TI  - Antimicrobial activity of melanoidins against Escherichia coli is mediated by a
      membrane-damage mechanism.
AB  - Melanoidins are brown polymeric material formed during thermal processing of food
      and widely distributed in the Western diet. Three water-soluble fractions were
      isolated from both commercial coffee and biscuit by sequential ultrafiltration
      steps (3 and 10 kDa cutoff). Biscuits were enzymatically digested to solubilize
      the protein-linked melanoidin fraction. Antimicrobial activity of melanoidins was
      evaluated against a Gram-negative reference pathogenic bacterium (Escherichia
      coli). The high-molecular-weight fraction of water-soluble melanoidins (>10 kDa)
      exerted the highest antimicrobial activity. The mechanism of action was further
      investigated by cell integrity and outer- and inner-membrane permeabilization
      assays. At the minimum inhibitory concentration, melanoidins provoked
      irreversible cell membrane disruption, which was independent of the bacterial
      transmembrane potential. Results indicate that water-soluble melanoidins killed
      pathogenic bacteria strains ( E. coli) by causing irreversible changes in both
      the inner and outer membranes. Likely, it allows for interference with
      biosynthetic processes, such as the inhibition of nutrient transport and
      macromolecular precursors.

PMID- 18338865
TI  - Multiscale characterization of the organization of triglycerides and
      phospholipids in emmental cheese: from the microscopic to the molecular level.
AB  - The chemical composition and properties of lipids, both triglycerides and
      phospholipids, play a major role in the functional and nutritional properties of
      food products. In this study, the suprastructure of fat, solid fat content, and
      crystallographic properties of triglycerides were investigated in hard-type
      cheeses from the microscopic scale to the molecular level using the combination
      of relevant techniques. Two industrial cheeses with different oiling off
      properties were compared with experimental cheeses manufactured in the
      laboratory. Microstructural analysis performed using confocal laser scanning
      microscopy showed that milk processing led to the disruption of fat globules with
      the formation of nonglobular fat. For a similar fatty acid composition, oiling
      off was mainly related to the fat in dry matter content and to the suprastructure
      of fat in cheese. An exogenous fluorescent phospholipid permitted the
      localization of milk phospholipids in the cheese matrix, which mainly remain
      around fat inclusions after disruption of the milk fat globule membrane, and to
      show heterogeneities. We also showed using differential scanning calorimetry that
      the suprastructure of fat did not affect the solid fat content in cheese at 4
      degrees C: 71.6 +/- 4.9%. The organization of triglyceride molecules in fat
      crystals, elucidated at a molecular level using X-ray diffraction, corresponded
      to the coexistence of 2 lamellar structures (2L 40.5 angstroms and 3L 54.6
      angstroms) with four polymorphic forms: alpha, two beta' and beta. A schematic
      representation of the multiscale organization of triglycerides and phospholipids
      in cheese is proposed.

PMID- 18338866
TI  - One- and two-dimensional direct chiral liquid chromatographic determination of
      mixtures of diclofop-Acid and diclofop-methyl herbicides.
AB  - Simple one- and two-dimensional high-performance liquid chromatography (HPLC)
      methods for the simultaneous enantiomeric determination of
      alkyloxyphenoxypropionic acid herbicides is presented. Compounds studied were (
      R, S)-2-[4-(2,4-dichlorophenoxy)phenoxy]propionic acid (diclofop-acid) and ( R,
      S)-2-[4-(2,4-dichlorophenoxy)]methyl propionate (diclofop-methyl). Mobile phases
      necessary to separate their enantiomers on an alpha1-acid glycoprotein chiral
      stationary phase are different; therefore, the simultaneous separation by an
      isocratic mode is not possible. The chiral separation method proposed involves a
      one-step gradient allowing for the simultaneous determination of both racemic
      enantiomers. Detection limits of the method were 0.03 mg/L for both diclofop-acid
      enantiomers and 0.14 and 0.15 mg/L for diclofop-methyl enantiomers, respectively.
      The two-dimensional method involves the use of two chromatographs in one achiral
      chiral coupling. The LC-LC method is more suitable for complex samples because it
      involves an online cleanup effect. Detection limits were 1.25 and 1.87 mg/L for
      diclofop-acid and 2.70 and 3.02 mg/L for diclofop-methyl enantiomers,
      respectively. Accuracy, repeatability, and reproducibility have been studied in
      standard samples and a technical product.

PMID- 18338867
TI  - The chemical characterization of the aroma of dessert and sparkling white wines
      (Pedro Ximenez, Fino, Sauternes, and Cava) by gas chromatography-olfactometry and
      chemical quantitative analysis.
AB  - Wines from Pedro Ximenez (PX), Fino, botrytized Sauternes, and Cava were screened
      by gas chromatography-olfactometry (GC-O), and the most relevant aroma compounds
      were further quantified in six different wines of each group. The comparison of
      GC-O and quantitative data with similar data from white young wines has made it
      possible to identify the aroma compounds potentially responsible for the specific
      sensory characteristics of these wines. Results have shown that all these wines
      are relatively rich in 3-methylbutanal, phenylacetaldehyde, methional, sotolon,
      and the ethyl esters of 2-, 3-, and 4-methylpentanoic acids. While Cava has a
      less specific aroma profile halfway between these special wines and young white
      wines, PX is richest in 3-methylbutanal, furfural, beta-damascenone, ethyl
      cyclohexanoate, and sotolon; Fino in acetaldehyde, diacetyl, ethyl esters of
      branched aliphatic acids with four, five, or six carbon atoms, and 4
      ethylguaiacol; and Sauternes in phenylacetaldehyde, 3-mercaptohexanol, and 4
      methyl-4-mercaptopentanone.

PMID- 18338868
TI  - Synthesis of photosynthesis-inhibiting nostoclide analogues.
AB  - A series of 34 3-benzyl-5-(arylmethylene)furan-2(5H)-ones, designed using the
      naturally occurring toxins nostoclides as a lead structure, was synthesized as
      potential inhibitors of the photosynthetic electron transport. All compounds were
      fully characterized by IR, NMR (1H and 13C), and MS spectrometry. HMBC and HSQC
      bidimensional experiments allowed 13C and 1H assignments. Their biological
      activities were evaluated in vitro as the ability to interfere with light-driven
      reduction of ferricyanide by isolated spinach chloroplasts. About two-thirds of
      the compounds exhibited inhibitory properties in the micromolar range against the
      basal electron flow from water to K3[Fe(CN)6]. The inhibitory potential of these
      3-benzyl-5-(arylmethylene)furan-2(5H)-one lactones is higher than that of other
      nostoclide analogues previously synthesized in the same laboratories.

PMID- 18338869
TI  - Diversity of polyketide synthases found in the Aspergillus and Streptomyces
      genomes.
AB  - Natural products produced by biological organisms have played an important role
      in human health. The genomes of several Aspergillus species and several
      Streptomyces species have recently been sequenced. Interestingly the genomes
      revealed a large range of secondary metabolite genes, for many of which the
      products are currently unknown, suggesting that there is a wealth of secondary
      metabolites yet to be discovered. This brief review will discuss the current
      knowledge in polyketides produced by the various different classes of polyketide
      synthases (PKSs) present in the Aspergillus and Streptomyces genomes.

PMID- 18338870
TI  - Distance dependent spectral tuning of two coupled metal nanoparticles.
AB  - The spectral properties of two spherical metallic nanoparticles of 80 nm in
      diameter are examined with regard to the interparticle distance and relative
      polarization of the excitation light. One Au nanoparticle is attached to a
      scanning fiber probe and the second to a scanning substrate. This configuration
      allows three-dimensional and arbitrary manipulation of both distance and relative
      orientation with respect to the incident light polarization. As supported by
      numerical simulations, a periodic modulation of the coupled plasmon resonance is
      observed for separations smaller than 1.5 microm. This interparticle coupling
      affects the scattering cross section in terms of spectral position and spectral
      width as well as the integral intensity of the Mie-scattered light.

PMID- 18338871
TI  - Highly dense and perfectly aligned single-walled carbon nanotubes fabricated by
      diamond wire drawing dies.
AB  - We have developed a low-cost and effective method to align single-walled carbon
      nanotubes (SWNTs) using a series of diamond wire drawing dies. The obtained SWNTs
      are highly dense and perfectly aligned. X-ray diffraction (XRD) indicates that
      the highly dense and perfectly aligned SWNTs (HDPA-SWNTs) form a two-dimensional
      triangular lattice with a lattice constant of 19.62 A. We observe a sharp (002)
      reflection in the XRD pattern, which should be ascribed to an intertube spacing
      3.39 A of adjacent SWNTs. Raman spectra reveal that the radical breath mode (RBM)
      of SWNTs with larger diameter in the HDPA-SWNTs is suppressed compared with that
      of as-grown SWNTs. The HDPA-SWNTs have a large density, approximately 1.09 g/cm
      3, and a low resistivity, approximately 2 m Omega cm, at room temperature, as
      well as a large response to light illumination.

PMID- 18338872
TI  - Lotus effect in engineered zirconia.
AB  - Patterned micro- and nanostructured surfaces have received increasing attention
      because of their ability to tune the hydrophobicity and hydrophilicity of their
      surfaces. However, the mechanical properties of these studied surfaces are not
      sufficiently robust for load-bearing applications. Here we report transparent
      nanocrystalline ZrO 2 films possessing combined properties of hardness and
      complete wetting behavior, which are expected to benefit tribology, wear
      reduction, and biomedical applications where ultrahydrophilic surfaces are
      required. This ultrahydrophilic behavior may be explained by the Wenzel model.

PMID- 18338873
TI  - Electrogenerated chemiluminescence DNA biosensor based on hairpin DNA probe
      labeled with ruthenium complex.
AB  - A highly selective electrogenerated chemiluminescence (ECL) biosensor for the
      detection of target single-strand DNA (ss-DNA) was developed using hairpin DNA as
      the recognition element and ruthenium complex as the signal-producing compound.
      The ECL-based DNA biosensor was fabricated by self-assembling the ECL probe of
      thiolated hairpin DNA tagged with ruthenium complex on the surface of a gold
      electrode. In the absence of target ss-DNA, the ECL probe immobilized on the
      surface of the electrode was in the folded configuration in which its termini
      were held in close proximity to the electrode, and thus a strong ECL signal could
      be generated. In the presence of target ss-DNA, a stem-loop of the ECL probe on
      the electrode was converted into a linear double-helix configuration due to
      hybridization, resulting in the tag moving away from the electrode surface, which
      in turn decreased the ECL signal. The ECL intensity of the DNA biosensor
      generated a "switch off" mode, which decreased with an increase of the
      concentration of target DNA, and a detection limit of 9 x 10(-11) M complementary
      target ss-DNA was achieved. Single mismatched target ss-DNA was effectively
      discriminated from complementary target ss-DNA. The effect of different loop
      lengths of the hairpin DNA on the selectivity of the ECL DNA biosensor has been
      investigated. This work demonstrated that the sensitivity and specificity of an
      ECL DNA biosensor could be greatly improved using a hairpin DNA species which has
      an appropriate stem and loop length as the recognition element.

PMID- 18338874
TI  - Ab initio study of the interaction of CHX3 (X = H, F, Cl, or Br) with benzene and
      hexafluorobenzene.
AB  - In this paper, the results of a study of the interaction of methane, fluoroform,
      chloroform, and bromoform with benzene and hexafluorobenzene are presented. The
      benzene complexes were studied at the MP2/6-31G(d) and MP2/6-311++G(2d,p) levels,
      and the hexafluorobenzene complexes were only studied at the MP2/6-31G(d) level.
      The optimized geometries, stabilization energies, potential energy surfaces,
      harmonic frequencies, and vibrational intensities are reported. A net attraction
      is predicted for all four benzene complexes, whereas for the CHX3.C6F6 complexes,
      it was found that MP2/6-31G(d) predicts a net attraction for the CH4, CHCl3, and
      CHBr3 complexes and does not predict a stable complex for CHF3.C6F6. The three
      complexes with net attractions all have blue-shifts of the CHX3 CH stretching
      wavenumber and a slight contraction (0.001-0.003 A) of the CH bond in CHX3. The
      MP2/6-31G(d) level predicts that the intensity of the CHX3 CH stretch will vary
      widely. For CH4.C6H6 and CHF3.C6H6, it is predicted that the intensity will be
      smaller for the complexes than the free molecules, whereas for the other
      complexes, anywhere from a 30% increase to an increase of 87 times is predicted.
      The atoms in molecules analysis showed that only three of the eight criteria for
      normal hydrogen bonding are satisfied for all eight complexes studied. Criterion
      3 (value of the Laplacian at the bond critical point) is not satisfied for any of
      the eight complexes.

PMID- 18338875
TI  - Polarity dependence of the radiative and nonradiative rates of flavone
      derivatives comprising structurally similar amino moieties: change in the nature
      of the emitting state.
AB  - Photophysical behavior of several structurally related electron donor-acceptor
      flavone derivatives, which have been synthesized and characterized, has been
      studied as a function of the polarity of the media. Significant variation of the
      absorption and fluorescence response of the systems has been observed with change
      in the polarity of the medium. The results show an increase in the radiative rate
      constant and a decrease in the nonradiative rate constant of the systems with
      increase in the polarity of the media. This finding has been attributed to the
      change in the nature of the emitting state from a mixed n-pi* and pi-pi* state to
      a dominant pi-pi* state with increase in the polarity of the medium. The results
      of single-crystal diffraction studies and theoretical calculations based on
      density functional method support the idea of close proximity of the n-pi* and pi
      pi* states and the change in their relative contributions toward the emission
      process with the polarity of the medium. Laser flash photolysis studies show that
      the triplet state is not involved in the variation of the fluorescence response
      of the systems.

PMID- 18338876
TI  - Assessing the performance of density functional theory for the electronic
      structure of metal-salens: the 3d(0)-metals.
AB  - A series of metal-salen complexes of the 3d(0) metals Sc(III), Ti(IV), V(V),
      Cr(VI), and Mn(VII) have been explored using high-level electronic structure
      methods including coupled-cluster theory with singles, doubles, and perturbative
      triples as well as complete active-space third-order perturbation theory. The
      performance of three common density functional theory approaches has been
      assessed for both the geometries and the relative energies of the low-lying
      electronic states. The nondynamical correlation effects are demonstrated to be
      extremely large in all of the systems examined. Although density functional
      theory provides reasonable results for some of the systems, the overall agreement
      is quite poor. This said, the density functional theory approaches are shown to
      outperform the single-reference perturbation theory and coupled-cluster theory
      approaches for cases of strong nondynamical correlation.

PMID- 18338877
TI  - Differential mobility separation of ions using a rectangular asymmetric waveform.
AB  - The performance of a planar differential mobility spectrometer (DMS) is
      investigated when operated in air at ambient pressure and driven by a rectangular
      asymmetric waveform, limited to frequencies of <1.2 MHz and voltage pulse
      amplitudes of <1 kV with steep rise times of the order of approximately 15 ns.
      Independent control of frequency, voltage pulse amplitude, and duty cycle allow
      for characterizing the DMS in terms of transmission, resolution and separation.
      The tradeoff between sensitivity and resolution and the effect of duty cycle on
      instrument performance are demonstrated experimentally. The dependence of ion
      mobility on the magnitude of the electric field determines the displacement of
      ions measured by the DC compensation voltage as a function of the duty cycle.
      Optimum values for the duty cycle exist for the separation of A- and C-type ions,
      while, B-type ions exhibit a more complex behavior. An analytical expression for
      describing the effect of duty cycle on the separation of the ions, determined by
      variations in the compensation voltage, is developed and compared to experimental
      results obtained in air below 75 Td using estimated alpha parameters for a set of
      ketones. In this context, errors associated with the calculation of alpha
      parameters using polynomials of even powers are highlighted.

PMID- 18338878
TI  - Quantum mechanical calculations for the H2O + hnu --> O(1D) + H2
      photodissociation process.
AB  - Quantum mechanical wavepacket calculations for the photodissociation of water in
      the second absorption band are presented. Using O + H2 Jacobi coordinates,
      partial cross sections for the O(1D) + H2 channel are calculated for different
      initial rotational states. Conical intersection and Renner-Teller effects are
      included. The branching ratios for the four accessible dissociation channels at
      121.6 nm are in good agreement with experiment (J. Chem. Phys. 1982, 77, 2432).
      The calculations predict significant rotational and vibrational excitation of the
      H2 fragments. Photodissociation of ortho and para water produces predominantly,
      but not exclusively, ortho and para H2 fragments, respectively.

PMID- 18338879
TI  - Roles of chain conformation and interpenetration in the growth of a
      polyelectrolyte multilayer.
AB  - In the present study, we have investigated the growth of a multilayer formed by
      poly(sodium 4-styrene sulfonate) (PSSS) and poly(diallyldimethylammonium
      chloride) (PDDA) at different salt concentrations by use of quartz crystal
      microbalance with dissipation (QCM-D). The frequency change (Deltaf) demonstrates
      that the exponential growth mode gradually becomes dominant as NaCl concentration
      (C(NaCl)) increases. On the other hand, the dissipation change (DeltaD) reveals
      that the deposition is dominated by chain conformation at C(NaCl) < 1.0 M, where
      the change of the characteristic growth parameter agrees well with the results
      fit with Debye length. At C(NaCl) > or = 1.0 M, the growth is not determined by
      chain conformation but by chain interpenetration.

PMID- 18338880
TI  - Molecular selectivity and immiscibility during the crystallization of mixtures of
      a set of homologous self-assembling molecules.
AB  - Utilizing self-assembly to create supramolecular structures is an active area at
      this time. Hybrid materials created by blending or doping, e.g.,
      organic/inorganic or donor/acceptor complexes are of great interest in the design
      of novel materials systems. The effect of mixing of any two self-assembling
      molecules to modify the properties and to understand if the process of blending
      changes the nature of the self-assembly would be of interest. We discuss here the
      effect of blending of two (hydrogen bond mediated) self-assembling homologous
      molecules on the structure and morphology. Materials that are candidate vehicles
      for phase-change inkjet technology, biscarbamates with alkyl side chains, are
      chosen for this study. Thermal analysis and IR spectra indicate that, when two
      biscarbamates differing only in the length of the alkyl chain are blended, the
      two components are immiscible, although they are chemically similar. There is no
      intercalation of the alkyl chains and cocrystallization. They are thus an example
      of a self-sorting system. The extent of hydrogen bonding and the packing of the
      alkyl chains are not affected. However, each serve as a nucleating agent and
      reduce the size of the spherulites and crystallinity. The spherulitic growth rate
      decreases upon blending. Partial melting experiments show that the spherulites of
      each component do not form independently, but are intermixed, implying that one
      acts as the nucleating sites for the other. Thus, although these are self
      sorting, the components in the mixture affect the morphology of each other upon
      crystallization. The behavior of this small molecule mixture is compared with
      those of hydrogen-bonded polymer blends. Studies of this nature on blends of self
      assembling molecules are expected to be important in materials design for
      optimizing properties.

PMID- 18338881
TI  - High-resolution spectroscopy of methyl 4-hydroxycinnamate and its hydrogen-bonded
      water complex.
AB  - The electronic structure and spectroscopic properties of the lower excited
      singlet states of methyl 4-hydroxycinnamate, a model for the chromophore of the
      photoactive yellow protein in neutral form, have been investigated using various
      high-resolution gas-phase spectroscopic techniques and quantum-chemical
      calculations. The experiments show that under our experimental conditions the
      molecule can adopt four conformations with similar spectroscopic properties. From
      the detailed assignment of the vibrationally active modes in excitation and
      emission spectra, it is concluded that the S(1) and S(2) states should be
      assigned to the V' and V pipi* states that are characterized by, respectively,
      small and large contributions of the HOMO --> LUMO excitation. We find that
      complexation with a single water molecule affects the spectroscopic properties of
      methyl 4-hydroxycinnamate considerably in terms of stabilization of the lowest
      excited singlet state but in particular with respect to the transition
      intensities. The latter observation is tentatively interpreted as being caused by
      an increase in the oscillator strength of the respective electronic transition as
      well as by a rise/removal of conical intersections with the pisigma* state.

PMID- 18338882
TI  - Balance of forces in simulated bilayers.
AB  - Two kinds of simulated bilayers are described, and the results are reported for
      lateral tension and for partial contributions of intermolecular forces to it.
      Data for the widest possible range of areas per surfactant head, from tunnel
      formation through tensionless state, transition to floppy bilayer, and its
      disintegration, are reported and discussed. The significance of the tensionless
      state is discussed.

PMID- 18338883
TI  - Polycationic beta-cyclodextrin "click clusters": monodisperse and versatile
      scaffolds for nucleic acid delivery.
AB  - Herein, a novel series of multivalent polycationic beta-cyclodextrin "click
      clusters" with discrete molecular weight have been synthesized, characterized,
      and examined as therapeutic pDNA carriers. The materials were creatively designed
      based on a beta-cyclodextrin core to impart a biocompatible multivalent
      architecture and oligoethyleneamine arms to facilitate pDNA binding,
      encapsulation, and cellular uptake. An acetylated-per-azido-beta-cyclodextrin (4)
      was reacted with series of alkyne dendrons (7a-e) (containing one to five
      ethyleneamine units) using copper-catalyzed 1,3-dipolar cycloaddition, to form a
      series of click clusters (9a-e) bearing 1,2,3-triazole linkers. Gel
      electrophoresis experiments, dynamic light scattering, and transmission electron
      microscopy revealed that the macromolecules bind and compact pDNA into spherical
      nanoparticles in the size range of 80-130 nm. The polycations protect pDNA
      against nuclease degradation, where structures 9c, 9d, and 9e did not allow pDNA
      degradation in the presence of serum for up to 48 h. The cellular uptake profiles
      were evaluated in Opti-MEM and demonstrate that all the click clusters
      efficiently deliver Cy5-labeled pDNA into HeLa and H9c2 (2-1) cells, and
      compounds 9d and 9e yielded efficacy similar to that of the positive controls,
      Jet-PEI and Superfect. Furthermore, the luciferase gene delivery experiments
      revealed that the level of reporter gene expression increased with an increase in
      oligoethyleneamine number within the cluster arms. The cytotoxicity profiles of
      these materials were evaluated by protein, MTT, and LDH assays, which demonstrate
      that all the click clusters remain nontoxic within the expected dosage range
      while the positive controls, Jet PEI and Superfect, were highly cytotoxic. In
      particular, 9d and 9e were the most effective and promising polycationic vehicles
      to be further optimized for future systemic delivery experiments.

PMID- 18338884
TI  - Direct measurement of the rate of interconversion of zirconaaziridine
      enantiomers.
AB  - The insertion of enantiopure C2-symmetric diphenylethylene carbonate into the Zr
      C bonds of zirconaaziridines leads to the asymmetric synthesis of amino acid
      methyl esters. Because the zirconaaziridine enantiomers interconvert, the
      reaction is a dynamic kinetic resolution (DKR). The efficiency of the DKR (the
      ratio of the two diastereomeric products) is determined by the balance between
      the rate of enantiomer interconversion and the rate of insertion; slow addition
      of the inserting enantiopure carbonate is often required to maximize the
      stereoselectivity. For a case when enantiomer interconversion is fast, its rate
      constant kinv has been determined by NMR line broadening; for a case when
      interconversion is slow, k(inv) has been determined by computer simulation of the
      formation of the diastereomeric products as a function of time; for several
      intermediate cases, k(inv) has been determined by making the zirconaaziridine
      enantioenriched and monitoring its racemization by CD spectroscopy. The observed
      k(inv) is independent of [THF], implying that interconversion occurs with THF
      coordinated. Interconversion presumably occurs via an achiral intermediate,
      either a rapidly inverting (via an eta1-N structure) eta3-azaallyl hydride or an
      eta1-imine. As addition of THF slows insertion without affecting enantiomer
      interconversion, it produces a more efficient DKR without slow addition of the
      enantiopure carbonate.

PMID- 18338885
TI  - In situ generation of a bisubstrate analogue for protein arginine
      methyltransferase 1.
AB  - Protein arginine methyltransferases (PRMTs) are (S)-adenosylmethionine (SAM)
      dependent methyltransferases that catalyze the post-translational methylation of
      Arg residues in a variety of different proteins involved in transcriptional
      regulation and RNA splicing (e.g., histones H2A, H3, and H4). Herein, we describe
      the use of an N-mustard, 5'-(diaminobutyric acid)-N-iodoethyl-5'-deoxyadenosine
      ammonium hydrochloride (AAI), to generate a bisubstrate analogue inhibitor of
      PRMT1. Using the approach outlined in this communication, it should be possible
      to generate bisubstrate analogue-based inhibitors of PRMT isozymes that are
      potent and highly selective for a particular isozyme. The fact that PRMT1
      catalyzes AAI transfer is also significant because with appropriate modifications
      (e.g., functionalization with pendant azido or alkyne functionalities) this
      compound could be used for proteomic applications to identify novel PRMT
      substrates.

PMID- 18338886
TI  - C60/corannulene on Cu(110): a surface-supported bistable buckybowl-buckyball host
      guest system.
AB  - Corannulene (COR) buckybowls were proposed as near ideal hosts for fullerene C60,
      but direct complexation of C60 and COR has remained a challenge in supramolecular
      chemistry. We report the formation of surface-supported COR-C60 host-guest
      complexes by deposition of C60 onto a COR lattice on Cu(110). Variable
      temperature scanning tunneling microscopy studies reveal two distinctly different
      states of C60 on the COR host lattice, with different binding energies and bowl
      ball separations. The transition from a weakly bound precursor state to a
      strongly bound host-guest complex is found to be thermally activated. Simple
      model calculations show that this bistability originates from a subtle interplay
      between homo- and heteromolecular interactions.

PMID- 18338887
TI  - Single molecule conformational dynamics of adenylate kinase: energy landscape,
      structural correlations, and transition state ensembles.
AB  - We developed a coarse grained two-well model to study the single molecule protein
      conformational dynamics in microscopic detail at the residue level, overcoming
      the often encountered computational bottleneck. In particular, we explored the
      underlying conformational energy landscape of adenylate kinase, a crucial protein
      for signal transduction in the cell, and identified two major kinetic pathways
      for the conformational switch between open and closed states through either the
      intermediate state or the transient state. Based on the parameters fitted to the
      room-temperature experimental data, we predicted open and closed kinetic rates at
      the whole temperature ranges from 10 to 50 degrees C, which agree well with the
      experimental turnover numbers. After uncovering the underlying mechanism for
      conformational dynamics and exploring the structural correlations, we found the
      crucial dynamical interplay between the nucleoside monophosphate binding domain
      (NMP) and the ATP-binding domain (LID) in controlling the conformational switch.
      The key residues and contacts responsible for the conformational transitions are
      identified by following the time evolution of the two-dimensional spatial contact
      maps and characterizing the transition state as well as intermediate structure
      ensembles through phi value analysis. Our model provides a general framework to
      study the conformational dynamics of biomolecules and can be applied to many
      other systems.

PMID- 18338888
TI  - Proton transfers in aromatic and antiaromatic systems. How aromatic or
      antiaromatic is the transition state? An ab initio study.
AB  - An ab initio study of six carbon-to-carbon identity proton transfers is reported.
      They refer to the benzenium ion/benzene (C6H7(+)/C6H6), the 2,4
      cyclopentadiene/cyclopentadienyl anion (C5H6/C5H5(-)), and the cyclobutenyl
      cation/cyclobutadiene (C4H5(+)/C4H4) systems and their respective noncyclic
      reference systems, that is, [structure: see text], [structure: see text] and
      [structure: see text]. For the aromatic C6H7(+)/C6H6 and C5H6/C5H5(-) systems,
      geometric parameters and aromaticity indices indicate that the transition states
      are highly aromatic. The proton-transfer barriers in these systems are quite low,
      which is consistent with a disproportionately high degree of transition-state
      aromaticity. For the antiaromatic C4H5(+)/C4H4 system, the geometric parameters
      and aromaticity indices indicate a rather small degree of antiaromaticity of the
      transition state. However, the proton-transfer barrier is higher than expected
      for a transition state with a low antiaromaticity. This implies that another
      factor contributes to the barrier; it is suggested that this factor is angle and
      torsional strain in the transition state. The question whether charge
      delocalization at the transition state might correlate with the development of
      aromaticity was also examined. No such correlation was found, that is, charge
      delocalization lags behind proton transfer as is commonly observed in nonaromatic
      systems involving pi-acceptor groups.

PMID- 18338889
TI  - Self-assembled donor comprising quantum dots and fluorescent proteins for long
      range fluorescence resonance energy transfer.
AB  - We report on the development of a self-assembled donor for long-range
      fluorescence resonance energy transfer (FRET). To this end, a three-chromophore
      FRET (3Ch-FRET) system was constructed, which consists of a luminescent quantum
      dot (QD), enhanced yellow fluorescent proteins (EYFP), and Atto647-dye-modified
      oligonucleotides. The system was assembled by electrostatic binding of covalent
      EYFP-ssDNA conjugate to the QD and subsequent hybridization with complementary
      oligonucleotides labeled with Atto647-dye. The final conjugates comprise three
      different two-chromophore FRET (2Ch-FRET) subsystems, QD/EYFP, QD/Atto647, and
      EYFP/Atto647, respectively, which were studied in detail by steady-state and time
      resolved photoluminescence measurements. The helicity of DNA allowed us to
      control donor/acceptor separations and thus enabled the detailed analysis of the
      various FRET processes. We found that the 2Ch-FRET and the 3Ch-FRET
      (QD/EYFP/Atto647) systems revealed FRET efficiencies and transfer rates that were
      affected by the availability of distinct FRET pathways. The derived energy
      transfer efficiencies and Forster radii indicated that within the 3Ch-FRET
      system, the 2Ch-FRET subsystem QD/EYFP showed highest FRET efficiencies ranging
      from 64 to 72%. Thus, it can be used as a powerful donor system that combines the
      intrinsic advantages of QDs (large and spectrally broad absorption cross section)
      and EYFP (high quantum yield) and enables long-distance FRET processes for donor
      acceptor distances of up to 13 nm.

PMID- 18338890
TI  - Coincidence of dynamical transitions in a soluble protein and its hydration
      water: direct measurements by neutron scattering and MD simulations.
AB  - The coupling between protein dynamics and hydration-water dynamics was assessed
      by perdeuteration, temperature-dependent neutron scattering, and molecular
      dynamics simulations. Mean square displacements of water and protein motions both
      show a broad transition at 220 K and are thus coupled. In particular, the protein
      dynamical transition appears to be driven by the onset of hydration-water
      translational motion.

PMID- 18338891
TI  - Asymmetric Ni-catalyzed conjugate allylation of activated enones.
AB  - The nickel-catalyzed enantioselective addition of allylboronic acid pinacol
      ester, allylB(pin), is described. This reaction is highly effective with
      dialkylidene ketones and favors the allylation of the benzylidene site in
      nonsymmetric substrates. The reaction appears to proceed by conversion of the
      dialkylidene ketone substrate to an unsaturated pi-allyl complex (I), followed by
      reductive elimination. Enantioselectivities range from 91 to 94% ee for a range
      of substrates when chiral ligand 14 is employed.

PMID- 18338892
TI  - A [3]rotaxane with two porphyrinic plates acting as an adaptable receptor.
AB  - Following a multistep procedure, the copper(I)-templated strategy allowed
      preparation of a multifunctional [3]rotaxane. The dumbbell consists of a central
      two-bidentate chelate unit and two terminal stoppers. The two rings threaded on
      the rotaxane axis consist each of a 1,10-phenanthroline-incorporating macrocycle,
      rigidly connected to an appended zinc-complexed porphyrin. The copper(I) template
      can be removed, affording a free rotaxane whose two rings can glide freely along
      the axis and spin around it. The dumbbell being very long (approximately 85 A in
      its extended conformation from one stopper to the other), the porphyrin-porphyrin
      distance can be varied over a wide range. The two porphyrinic plates constitute
      the key elements of a receptor able to complex various guests between the plates.
      The ability of the threaded rings to move freely makes the host perfectly
      adjustable, allowing capture of geometrically very different guests. The
      copper(I)-complexed rotaxane also acts as an efficient receptor, although its
      adaptability is obviously more limited than that of its free rotaxane
      counterpart.

PMID- 18338893
TI  - Ultra narrow PbS nanorods with intense fluorescence.
AB  - We report on the narrowest "free" quantum rods of PbS with 1.7 nm diameter
      produced in a single step under bench-top reaction conditions. The nanorods
      exhibit molecule-like discrete narrow optical behavior with high fluorescence
      quantum yield. We propose a new macroscopic vortex assembly formation by simple
      spin casting route. Interestingly, the pattern generates fluorescence along its
      line from the nanorod domains. The ultra narrow nanorods with strong discrete
      fluorescence and robust stability could be useful in biological labeling,
      fluorescence resonance energy transfer, and optoelectronics applications, as well
      as to verify the theories in the very strong confinement regime.

PMID- 18338894
TI  - Molecular modeling based approach to potent P2-P4 macrocyclic inhibitors of
      hepatitis C NS3/4A protease.
AB  - Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures
      proved to be a valuable tool in the design of a new series of potent NS3 protease
      inhibitors. Optimization of initial compounds provided 25a. The in vitro activity
      and selectivity as well as the rat pharmacokinetic profile of 25a compare
      favorably with the data for other NS3/4A protease inhibitors currently in
      clinical development for the treatment of HCV.

PMID- 18338895
TI  - Highly cis-1,4 selective polymerization of dienes with homogeneous Ziegler-Natta
      catalysts based on NCN-pincer rare earth metal dichloride precursors.
AB  - The first aryldiimine NCN-pincer ligated rare earth metal dichlorides (2,6-(2,6
      C6H3R2N=CH)2-C6H3)LnCl2(THF)2 (Ln = Y, R = Me (1), Et (2), iPr (3); R = Et, Ln =
      La (4), Nd (5), Gd (6), Sm (7), Eu (8), Tb (9), Dy (10), Ho (11), Yb (12), Lu
      (13)) were successfully synthesized via transmetalation between 2,6-(2,6-C6H3
      R2N=CH)2-C6H3Li and LnCl3(THF)(1-3.5). These complexes are isostructural monomers
      with two coordinating THF molecules, where the pincer ligand coordinates to the
      central metal ion in a kappaC:kappaN:kappaN' tridentate mode, adopting a
      meridional geometry. Complexes 1-6, 9-11, and 13 combined with aluminum
      tris(alkyl)s and [Ph3C][B(C6F5)4] established a homogeneous Ziegler-Natta
      catalyst system, which exhibited high activities and excellent cis-1,4
      selectivities for the polymerizations of butadiene (T(p) = 25 degrees C, 99.9%; 0
      degrees C, 100%) and isoprene (T(p) = 25 degrees C, 98.8%). Remarkably, such high
      cis-1,4 selectivity almost remained at elevated polymerization temperatures up to
      80 degrees C and did not vary with the type of the central lanthanide element,
      however, which was influenced obviously by the ortho substituent of the N-aryl
      ring of the ligands and the bulkiness of the aluminum alkyls. The Ln-Al
      bimetallic cations were considered as the active species. These results shed new
      light on improving the catalytic performance of the conventional Ziegler-Natta
      catalysts for the specific selective polymerization of dienes.

PMID- 18338896
TI  - Simultaneously cycled NMR spectroscopy.
AB  - Simultaneously cycled (SC) NMR was introduced and exemplified by implementing a
      set of 2-D [1H,1H] SC exclusive COSY (E.COSY) NMR experiments, that is, rf pulse
      flip-angle cycled (SFC), rf pulse phase cycled (SPC), and pulsed field gradient
      (PFG) strength cycled (SGC) E.COSY. Spatially selective 1H rf pulses were applied
      as composite pulses such that all steps of the respective cycles were affected
      simultaneously in different slices of the sample. This increased the data
      acquisition speed for an n-step cycle n-fold. A high intrinsic sensitivity was
      achieved by defining the cycles in a manner that the receiver phase remains
      constant for all steps of the cycle. Then, the signal resulting from applying the
      cycle corresponded to the sum of the signals from all steps of the cycle. Hence,
      the detected free induction decay did not have to be separated into the
      contributions arising from different slices, and read-out PFGs, which not only
      greatly reduce sensitivity but also negatively impact lineshapes in the direct
      dimension, were avoided. The current implementation of SFC E.COSY reached
      approximately 65% of the intrinsic sensitivity of the conventional phase cycled
      congener, making this experiment highly attractive whenever conventional data
      acquisition is sampling limited. Highly resolved SC E.COSY yielding accurate 3J
      coupling values was recorded for the 416 Da plant alkaloid tomatidine within 80
      min, that is, 12 times faster than with conventional phase cycled E.COSY. SC NMR
      is applicable for a large variety of NMR experiments and thus promises to be a
      valuable addition to the arsenal of approaches for tackling the NMR sampling
      problem to avoid sampling limited data acquisition.

PMID- 18338897
TI  - Chirality of amyloid suprastructures.
AB  - Amyloids are pathological fibrillar aggregates of proteins related to more than
      20 different diseases. Amyloid fibers have a characteristic cross-beta structure
      consisting of a series of beta-strands extended perpendicular to the fiber axis
      and joined by hydrogen bonds parallel to the fiber direction. Fibril aggregation
      results in helical suprastructures. Here we used high-resolution SEM and cryo-SEM
      for the study of chirality in the amyloid suprastructure. We found that amyloids
      of Abeta1-40 and hen lysozyme form at all hierarchical levels always and only
      left-handed helices. In contrast, amyloid fibers formed by the N-terminal
      sequence of serum amyloid A (SAA1-12) consist of right-handed helices
      exclusively. Consistently, the peptide enantiomer, formed of (R)-aminoacids,
      aggregates exclusively in left-handed helices. We conclude that the opposite
      handedness of the SAA1-12 amyloids is an intrinsic feature of the peptide
      structure. The left-handed chirality observed for the Abeta1-40 and hen lysozyme
      amyloid suprastructures is consistent with the conventional beta-sheet structural
      model. In contrast, the right-handedness observed in (all-S) SAA1-12 fibers
      indicates that the cross-beta structure of SAA1-12 fibers is probably not formed
      of beta-sheets. Whatever the answer to the dilemma of the right-handed helicity
      of SAA1-12 amyloid fibers is, its existence shows that the supramolecular
      chirality of amyloid fibers is not only dictated by the molecular chirality of
      the component molecules but also by their structural organization.

PMID- 18338898
TI  - Synthesis of new fluorogenic cyanine dyes and incorporation into RNA
      fluoromodules.
AB  - A new fluorogenic cyanine dye was synthesized and found to have low fluorescence
      quantum yield in fluid solution and in the presence of double-stranded DNA but 80
      fold enhanced fluorescence in viscous glycerol solution. An RNA aptamer selected
      for binding to the new dye exhibits K(d) = 87 nM and 60-fold fluorescence
      enhancement. The dye-aptamer pair is a fluoromodule that can be incorporated into
      fluorescent sensors and labels.

PMID- 18338899
TI  - Cycloaddition of arynes with iodonium ylides: a mild and general route for the
      synthesis of benzofuran derivatives.
AB  - A mild and general cycloaddition of arynes with iodonium ylides protocol has been
      developed for the synthesis of benzofurans. In the presence of CsF, ortho-silyl
      aryltriflates were reacted with iodonium ylides smoothly at room temperature in
      moderate to good yields.

PMID- 18338900
TI  - Total synthesis of (+)-brefeldin A.
AB  - (+)-Brefeldin A was synthesized through an efficient route, which features (1)
      construction of the five-membered ring from a Crimmins aldol via tandem Li-I
      exchange and carbanion-mediated cyclization with concurrent removal of the chiral
      auxiliary, (2) introduction of the lower side chain (C10 to C16) via a Rh
      catalyzed Michael addition of a vinyl boronic acid, (3) stereoselective reduction
      of the C7 ketone with SmI2, and (4) a 2-methyl-6-nitrobenzoic anhydride-mediated
      (Shiina) lactonization.

PMID- 18338901
TI  - Chemoselective hydrogenation of nitroarenes with carbon nanofiber-supported
      platinum and palladium nanoparticles.
AB  - Platinum and palladium nanoparticles supported on three types of carbon
      nanofibers (CNFs) are synthesized and used as catalysts in the hydrogenation of
      nitroarenes. Nanosized platinum particles dispersed on platelet-type CNF
      efficiently catalyze the reduction of functionalized nitroarenes to the
      corresponding substituted anilines in high turnover numbers with other functional
      groups remaining intact.

PMID- 18338902
TI  - A short enantioselective synthesis of N-Boc-(2R,3R)-3-methyl-3-hydroxypipecolic
      acid from geraniol.
AB  - The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key
      intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is
      described. The title compound is prepared in seven steps with an overall yield of
      41% starting from geraniol. Key steps in the synthesis include Sharpless
      asymmetric epoxidation, which establishes the chiral centers, and a one-pot
      oxidative olefin cleavage/reductive amination sequence that closes the piperidine
      ring.

PMID- 18338903
TI  - Protein surface mapping using diethylpyrocarbonate with mass spectrometric
      detection.
AB  - The reliability and information content of diethylpyrocarbonate (DEPC) as a
      covalent probe of protein surface structure has been improved when used
      appropriately with mass spectrometric detection. Using myoglobin, cytochrome c,
      and beta-2-microglobulin as model protein systems, we demonstrate for the first
      time that DEPC can modify Ser and Thr residues in addition to His and Tyr
      residues. This result expands the capability of DEPC as a structural probe
      because about 25% of the sequence of the average protein can now be covered using
      this covalent labeling reagent. In addition, we establish a new approach based on
      mass spectrometry to ensure the structural integrity of proteins during amino
      acid-specific covalent labeling reactions. This approach involves monitoring the
      extent of modification as a function of reagent concentration and allows any
      small-scale or local perturbations caused by the covalent label to be readily
      identified and avoided. Results indicate that these dose-response plots are much
      more reliable and generally applicable probes of possible protein structural
      changes than fluorescence or circular dichroism spectroscopies. These dose
      response plots also provide a means of quantitatively comparing the reactivity of
      each modified residue. On the basis of comparisons to known X-ray crystal
      structures, we find that the solvent accessibility of the reactive atom in the
      side chain and the presence of a nearby charged residue most affect modification
      rates. Finally, this improved surface mapping method has been used to determine
      the effect of Cu(II) binding on the structure of beta-2-microglobulin. Results
      confirm that Cu(II) binds His31, but not any of the other three His residues, and
      changes the solvent accessibility of residues near His31 and near the N-terminus.

PMID- 18338904
TI  - 13C CPMAS NMR spectroscopy as a versatile and quantitative tool for determination
      of mercury adsorption capacity in thiol-functionalized mesoporous silica SBA-1.
AB  - 13C cross-polarization magic angle spinning (CPMAS) NMR spectroscopy is
      demonstrated to be a valuable characterization tool for quantitative measurements
      of Hg2+ adsorption capacity in thiol-functionalized mesoporous silica SBA-1
      (Santa Barbara Amorphous-1). This is the first report on the investigation of the
      spectral change in the 13C CP signals for mercaptopropyl-functionalized
      mesoporous materials doped with different Hg2+ concentrations. The chemical shift
      of the carbon atom adjacent to the thiol group is sensitive to the binding of the
      mercury ion, and its peak intensity can be used as a quantitative sensor for the
      amount of the mercury ion adsorbed. The 13C CPMAS NMR results are in good
      agreement with inductively coupled plasma-atomic emission spectroscopy (ICP-AES)
      analysis.

PMID- 18338905
TI  - Utility of immonium ions for assignment of epsilon-N-acetyllysine-containing
      peptides by tandem mass spectrometry.
AB  - Tandem mass spectrometry (MS/MS) is a powerful tool for characterization of post
      translationally modified proteins, including epsilon-N-acetyllysine-containing
      species. Previous reports indicate that epsilon-N-acetyllysine immonium ions are
      useful marker ions for peptides containing epsilon-N-acetyllysine, but the
      specificity and sensitivity of these ions for assignment of lysine acetylation by
      MS/MS have not been studied in detail. We investigated MS/MS data sets of 172
      epsilon-N-acetyllysine tryptic peptides and 268 nonacetylated tryptic peptides to
      establish the utility and reliability of epsilon-N-acetyllysine immonium ions for
      identification and validation of acetylated peptides. Our analysis shows that the
      immonium ion at m/z 143 lacks specificity for lysine-acetylated peptides, whereas
      the derivative at m/z 126 is highly specific (98.1%). We also studied the
      positional effect of the epsilon-N-acetyllysine on the intensity of observed
      acetyllysine immonium ions. We observed an increase in acetyllysine immonium ion
      intensities when the acetylated lysine was N-terminally positioned in the peptide
      as compared to internal positions. Based on these observations we propose a
      validation scheme for unambiguous assignment of acetyllysine-containing peptides
      by MS/MS. Our analysis of epsilon-N-acetyllysine immonium ions provide a
      framework for investigation of MS/MS marker ion specificity and sensitivity that
      can be applied in studies of other types of post-translational modifications.

PMID- 18338906
TI  - Synthesis of hybrid gold-gold sulfide colloidal particles.
AB  - The nucleation and growth mechanism of nanometer size gold onto gold sulfide
      colloidal particles by irradiation-induced reduction is reported. The process is
      characterized by ultraviolet-visible spectroscopy, electronic diffraction, and
      high-resolution transmission electron microscopy, allowing for observation of
      several key intermediates and characteristics of the growth mechanism. The
      formation mechanism of gold on the surface of the gold sulfide particles is shown
      to depend strongly on the deposition rate. At low dose rate, gold nucleates
      preferentially onto specific gold-rich Au2S facets {110}, resulting in epitaxial
      growth. The gold crystal lattice plastically deforms near the interface to
      accommodate a substantial lattice mismatch. Upon increasing gold precursor
      concentration, this low dose rate results in growth of elongated gold island on
      the gold sulfide surface. At a high dose rate, several randomly oriented gold
      particles are simultaneously produced on gold sulfide, resulting in a layered
      structure. The absorption spectra of these particles show a dominant surface
      plasmon band, whose peak wavelength shifts markedly to the red as layered
      structure is formed.

PMID- 18338907
TI  - Phase behavior of ranitidine HCl in the presence of degradants and atmospheric
      moisture--impact on chemical stability.
AB  - For hydrophilic organic solids, it is well recognized that degradation is often
      promoted by exposure to humid conditions. Although this is an important issue for
      certain classes of materials, in particular pharmaceuticals, the factors which
      dictate the sensitivity of a given compound to moisture are not well understood.
      The goal of this work was to elucidate the synergistic influence of self
      originating impurities and water vapor on the degradation kinetics of the
      histamine H2 receptor antagonist, ranitidine HCl. Physical mixtures of the drug
      and each of three major degradation products were subjected to conditions of
      elevated temperature and relative humidities. Pure samples showed a sigmoidal
      shaped degradation profile for all storage conditions studied. During the lag
      time, the pure drug gained minimal quantities of moisture. Once degradation
      commenced, the samples started to absorb moisture. When mixed with the degradant,
      the lag period was eliminated for all storage conditions, even at low partial
      pressures of water. The extent of moisture gain by samples containing impurities
      could not be attributed to the presence of the impurity alone. It was found that
      the presence of impurities in contact with the surface of the drug, in
      combination with water vapor, promoted a phase transition of the crystalline
      material to the solution phase. A ternary phase diagram was constructed to
      visualize the proportion of the drug in the solid and solution phases as a
      function of impurity and moisture content. The increased mobility of molecules in
      solution presumably leads to enhanced reactivity relative to the crystalline
      material.

PMID- 18338908
TI  - Liposome-templated supramolecular assembly of responsive alginate nanogels.
AB  - Nanosized gel particles (nanogels) are of interest for a variety of applications,
      including drug delivery and single-molecule encapsulation. Here, we employ the
      cores of nanoscale liposomes as reaction vessels to template the assembly of
      calcium alginate nanogels. For our experiments, a liposome formulation with a
      high bilayer melting temperature (Tm) is selected, and sodium alginate is
      encapsulated in the liposomal core. The liposomes are then placed in an aqueous
      buffer containing calcium chloride, and the temperature is raised up to Tm. This
      allows permeation of Ca2+ ions through the bilayer and into the core, whereupon
      these ions gel the encapsulated alginate. Subsequently, the lipid bilayer
      covering the gelled core is removed by the addition of a detergent. The resulting
      alginate nanogels have a size distribution consistent with that of the template
      liposomes (ca. 120-200 nm), as confirmed by transmission electron microscopy and
      light scattering. Nanogels of different average sizes can be synthesized by
      varying the template dimensions, and the gel size can be further tuned after
      synthesis by the addition of monovalent salt to the solution.

PMID- 18338909
TI  - Molecular organization in SAMs used for neuronal cell growth.
AB  - The attachment of cells onto solid supports is fundamental in the development of
      advanced biosensors or biochips. In this work, we characterize cortical neuron
      adhesion, growth, and distribution of an adhesive layer, depending on the
      molecular structure and composition . Neuronal networks are successfully grown on
      amino-terminated alkanethiol self-assembled monolayer (SAM) on a gold substrate
      without adhesion protein interfaces. Neuron adhesion efficiency was studied for
      amino-terminated, carboxy-terminated, and 1:1 mixed alkanethiol SAMs deposited on
      gold substrates. Atomic force microscopy and X-ray photoelectron spectroscopy
      were used to measure the roughness of gold substrate and thickness of SAM
      monolayers. Conformational ordering and ionic content of SAMs were characterized
      by vibrational sum frequency generation (VSFG) spectroscopy. Only pure amino
      terminated SAMs provide efficient neuronal cell attachment. Ordering of the
      terminal amino groups does not affect efficiency of neuron adhesion. VSFG
      analysis shows that ordering of the terminal groups improves with decreasing
      surface roughness; however the number of gauche defects in alkane chains is
      independent of surface roughness. We monitor partial dissociation of carboxy
      groups in mixed SAMs that implies formation of NH3+ neighbors and appearance of
      catanionic structure. Such catanionic environment proved inefficient for neuron
      adhesion. Surface roughness of metal within the 0.7-2 nm range has little effect
      on the efficiency of neuron adhesion. This approach can be used to create new
      methods that help map structure-property relationships of biohybrid systems.

PMID- 18338910
TI  - High fluidity and soft elasticity of the inner membrane of Escherichia coli
      revealed by the surface rheology of model Langmuir monolayers.
AB  - We have studied the equilibrium and linear mechanical properties of model
      membranes of Escherichia coli built up as Langmuir monolayers of a native lipid
      extract using surface thermodynamics, fluorescence microscopy, and surface
      rheology measurements. The experimental study has been carried out at different
      temperatures across the physiological operative range 15-37 degrees C. Lipid
      phase coexistence has been revealed over a broad pressure range by fluorescence
      microscopy. The presence of ordered domains has been invoked to explain the
      emergence of shear elasticity accompanying the hydrostatic compression elasticity
      typical of fluid monolayers. The surface rheology measurements point out the soft
      character of E. coli membranes; i.e., upon deformation they react as a near-ideal
      compliant body with minimal energy dissipation, thus optimizing the effectiveness
      of external stresses in producing membrane deformations. These mechanical
      features appear to be independent of temperature, suggesting the existence of a
      passive thermoregulation mechanism.

PMID- 18338911
TI  - Comparative study of methane adsorption on graphite.
AB  - To study methane adsorption on graphite in a wide range of coverages and
      temperatures, we compare experimental results with Monte Carlo simulations (MCSs)
      of the grand canonical ensemble (GCE) and mean-field approximation (MFA) of the
      lattice gas model (LGM). MCSs were performed by employing two models for the
      substrate description; we utilized Steele's 10-4-3 analytical potential, and as a
      second approach, we represented the graphite surface as composed of several
      graphene layers (at the atomic level). We obtained adsorption isotherms and
      density profiles that confirm a layer-by-layer mechanism at low temperatures; the
      later results in the analytical model having a denser condensed phase than the
      atomistic one. LGM calculations show a close-packed lattice configuration and
      also allow us to describe the adsorption mechanism changes with temperature. The
      isosteric heat of adsorption that was found was approximately 13 kJ/mol. We can
      also conclude that, in spite of the greater computational cost, the atomistic
      model could be employed for surfaces that are not necessarily homogeneous and
      beyond the low-pressure range that are not covered by the simple, fast
      description given by the analytical model.

PMID- 18338912
TI  - Structural organization of gold nanoparticles onto the ITO surface and its
      optical properties as a function of ensemble size.
AB  - Self-assembly of citrate-stabilized gold nanoparticles (AuNPs) onto an optically
      transparent indium tin oxide (ITO) surface followed by neutralization of these
      particles using dodecanethiol as a surfactant have been demonstrated. X-ray
      photoelectron spectroscopic (XPS) studies revealed the partial removal of citrate
      ions from the immobilized AuNPs, which advances the dilution of electrostatic
      attraction between AuNPs and the APS (amino-terminated monolayer)-functionalized
      ITO surface. The resultant AuNPs restore their mobility to some extent and form
      small ensembles. Some of the immobilized AuNPs were completely removed from the
      surface due to neutralization, as confirmed by XPS studies. Interparticle
      distance and size of ensembles were manipulated by consecutive cycles of
      immobilization and neutralization of AuNPs. Controlled nanostructural fabrication
      progression, which leads to two-dimensional lateral growth of AuNPs, provides a
      method for systematically shifting the surface plasmon resonance band based on
      the increase in plasmon coupling among the closely placed AuNPs of an ensemble.
      The magnitude of shift increases with the size of ensemble. This manipulated
      chemical strategy offers a convenient and simple method to tune the optical
      properties of materials on a nanoscale.

PMID- 18338913
TI  - Paramagnetic liposomes: inner versus outer membrane relaxivity of DPPC liposomes
      incorporating lipophilic gadolinium complexes.
AB  - Proton relaxometric properties of unilamellar DPPC liposomes embedding an
      amphiphilic paramagnetic chelate (Gd-DTPA-BC(14)A) in both layers of the
      phospholipid membrane or only in the external one are compared. The results show
      that the membrane's water permeability is able to quench the effect of the
      paramagnetic complexes located in the internal layer of DPPC liposomes, leading
      thus to an apparent lower global relaxivity.

PMID- 18338914
TI  - [Mycoses and zoonoses: Cryptococcus spp].
AB  - The term "zoonosis" is difficult to delimit because different authors have
      various definitions for this term. Few mycoses are usually considered zoonoses.
      However, the role that animals play in the epidemiology of the main human mycoses
      is still not well known. Moreover, the environmental niches for these fungal
      agents have not yet been completely determined. This special issue of the
      "Revista Iberoamericana de Micologia" deals with the talks and round table
      presented at the VIII Spanish Mycological Congress held in October 2006 in
      Barcelona, Spain on "Cryptococcus spp. and zoonoses".

PMID- 18338915
TI  - [Pigeons and other birds as a reservoir for Cryptococcus spp].
AB  - In the last 25 years, the cases of human and animal cryptococcosis have increased
      significantly. This is mostly due to the improvement in the survival of
      immunocompromised patients. The disease is frequently related to the exposure of
      this type of patients to avian droppings. Among birds, pigeon, Columba livia, is
      undoubtedly the most important reservoir for the Cryptococcus species.
      Nevertheless, the study of a large number of bird's species demonstrated that
      pigeons are not the only Cryptococcus spp. carriers. The suspicion of the birds
      being the source for the infection is now becoming a demonstrable fact thanks to
      the use of molecular typing methods. These methods allow the comparison between
      strains from birds to patients living around them, with high level of
      discrimination.

PMID- 18338916
TI  - [Cryptococcosis and pets].
AB  - This paper is a review of cryptococcosis in domestic animals. Cryptococcosis is
      an uncommon mycosis in domestic animals and its occurrence is sporadic. The
      disease is caused by Cryptococcus neoformans, although Cryptococcus gattii has
      been also isolated from different animal species. Although cryptococcosis has
      been reported in several animal species, the most frequently affected domestic
      animal is the cat. The present paper deals with feline and canine cryptococcosis,
      its common clinical signs and the different clinical forms of the disease in
      these species. The diagnosis and treatment of cryptococcosis is also discussed.
      Diagnosis usually includes cytologic examination, capsular antigen detection and
      culture and identification of the Cryptococcus species. The management of
      criptococcosis will review the most common therapeutic agents and their role in
      therapy. Finally, we will address the situation of cryptococcosis in domestic
      animals in Spain and the role of cryptococcosis as a zoonotic disease and its
      public health importance.

PMID- 18338917
TI  - Diversity of the Cryptococcus neoformans-Cryptococcus gattii species complex.
AB  - More than 110 years of study of the Cryptococcus neoformans and Cryptococcus
      gattii species complex has resulted in an enormous accumulation of fundamental
      and applied biological and clinical knowledge. Recent developments in our
      understanding of the diversity within the species complex are presented,
      emphasizing the intraspecific complexity, which includes species, microspecies,
      hybrids, serotypes and genotypes. Each of these may have different roles in
      disease. An overview of obsolete and current names is presented.

PMID- 18338918
TI  - [At the first turning of the second stair I turned and saw: 25 years of Revista
      Iberoamericana de Micologia].

PMID- 18338919
TI  - Comparative evaluation of ATB Fungus 2 and Sensititre YeastOne panels for testing
      in vitro Candida antifungal susceptibility.
AB  - ATB Fungus 2 and SensititreYeastOne are commercial methods for antifungal
      susceptibility testing of yeasts. The agreement between these two methods was
      assessed with a total of 133 Candida strains (60 Candida albicans, 18 Candida
      dubliniensis, 29 Candida glabrata, and 26 Candida krusei). MIC endpoints were
      established after 24 h of incubation at 36-/+1 degrees C by each method. Intra
      laboratory reproducibility of both methods was excellent (=or>99%). Overall
      agreement between ATB Fungus 2 and Sensititre YeastOne 3 MICs (within 2
      dilutions) was 91.2-97.7% for amphotericin B, 5-fluorocytosine and itraconazole,
      and 82.7% for fluconazole. The categorical agreement when ATB Fungus 2 results
      were compared to those by SensititreYeastOne 3 was 93.2-98.5% for 5
      fluorocytosine and amphotericin B, but lower for the triazoles (72.9-75.9%). This
      easy to perform method could be an alternative for routine use in the clinical
      microbiology laboratory for susceptibility testing of common Candida spp.

PMID- 18338920
TI  - [Mycotoxin research in humans].
AB  - This study investigates the occurrence of aflatoxins in Ecuador. Early
      investigators proved the presence of aflatoxins in human and animal food, but the
      disturbing data lead to the formation of two research teams at Guayaquil
      University and the Agrarian University of Ecuador to investigate aflaxotins and
      other mycotoxins in food and their relationship to human health. Because the
      concept of mycotoxicosis as a result of the secondary metabolites produced by
      different species of moulds could cause different clinical patterns, the research
      team includes Aspergillus metabolites found in the urine of a patient with
      pulmonary aspergilloma. We considered that the body itself could create secondary
      metabolites. An ELISA method was used to detect mycotoxins with the specific
      reactive compounds using a company base assay. This allows the detection
      quantitative of such metabolites in 24 h collected urine. The patient was treated
      with itraconazole for nine months, after clinical, radiological and aflatoxins
      testing. We also investigated three other cases in children with a second level
      of malnutrition and only with vomitoxins results and in three investigated cases
      of otomycosis caused by Aspergillus niger only in one case traces of aflatoxins
      were found.

PMID- 18338921
TI  - [Protease and phospholipase activities of Candida albicans isolated from vaginal
      secretions with different pH values].
AB  - Even though vulvovaginal candidiasis and bacterial vaginosis are seldom
      simultaneously found, we have detected this association at an above average
      frequency. Thus, we set out to study the activity of proteinases and
      phospholipases, virulence factors of Candida albicans, to assess their role in
      the above mentioned association. Of a total of 70 Candida isolates were retrieved
      from samples of vaginal secretions analyzed at our Diagnostic Service, 65 were
      identified as C. albicans (a group of n=26 obtained from clinical samples of
      pH>4.5 and a group of n=39 from clinical samples of pH=or<4.5). The evaluation of
      phospholipases activity was performed on malt agar and Sabouraud dextrose agar
      with the addition of egg yolk as substrate. The proteolytic activity was detected
      on plates of agar base medium with the addition of bovine albumin serum as
      substrate as sole nitrogen source. Phospholipases activity was essentially the
      same in both groups of samples (p=0.2003). Proteolytic activity was detected in
      61.5% of the isolates from the group with pH=or<4.5 and in 96.2% in the group
      with pH>4.5; being the former much higher than the latter (p=0.0001). Based on
      these results we postulate that the simultaneous occurrence of bacterial
      vaginosis and vulvovaginal candidiasis could be related to the proteolytic
      activity but unrelated to phospholipases activity.

PMID- 18338922
TI  - [Distribution and antifungal susceptibility of Candida clinical isolations coming
      from six health care centers in the metropolitan area of Caracas, Venezuela
      (years 2003-2005)].
AB  - The aim of this study was to investigate the frequency and antifungal
      susceptibility of Candida clinical isolations coming from patients with
      candidiasis in six health care centers of Caracas, Venezuela metropolitan area.
      The laboratory reports were retrospectively revised from January 2003 through
      August 2005. The isolated yeasts identification was carried out by conventional
      methods and antifungal susceptibility was evaluated by ATB-fungus (bioMerieux,
      France) and Etest (AB Biodisk, Solna, Sweden). One thousand nine hundred seventy
      seven (1.977) yeasts were studied and their susceptibility testing were carried
      out only in 1,414 of them. C. albicans was the most isolated yeast (46.7%) and
      none-albicans Candida-species represented more than half of the isolations
      (53.4%). All the isolated yeasts evaluated presented CMIs<1 microg/ml to
      anfotericina B and showed variable susceptibility percentages to fluconazole
      (91.5%), itraconazole (80%) and voriconazole (98.6%).

PMID- 18338923
TI  - [Effect of Mexican propolis extracts from Apis mellifera on Candida albicans in
      vitro growth].
AB  - Propolis is a resinous substance collected by bees (Apis mellifera) from
      different trees and bushes. Due to its antifungal, antibacterial, antiviral and
      antiparasitic properties, it has continued to be very popular throughout the time
      showing variable activity depending on its geographical origin. In Mexico,
      information about this product is very limited. The aim of this work was to
      evaluate the antifungal activity of four propolis ethanolic extracts from three
      different Mexican states, and four commercial extracts on Candida albicans
      growth. A reference strain (ATCC 10231) and 36 clinical isolates of C. albicans
      were used. The Minimal Inhibitory Concentration (MIC) was determined by the
      dilution on agar method. Growth curves on Sabouraud Dextrose broth with and
      without different propolis ethanolic extracts concentrations were performed. In
      addition, whether the effect was fungistatic or fungicide was determined. The
      propolis ethanolic extract obtained from Cuautitlan Izcalli, State of Mexico,
      showed the best biological activity, inhibiting 94.4% from the clinical isolates
      at 0.8 mg/ml; the reference strain was inhibited at 0.6 mg/ml. The propolis
      effect was fungistatic in low concentrations and fungicide in concentrations
      higher to MIC. The Mexican propolis ethanolic extract could be further
      investigated for its alternative use for the treatment of some C. albicans
      infections.

PMID- 18338924
TI  - [Urease activity in Cryptococcus neoformans and Cryptococcus gattii].
AB  - Urease is an enzyme considered one of the main virulence factors in Cryptococcus
      neoformans. Quantitative differences in urease production between C. neoformans
      and the new species Cryptococcus gattii have not been so far documented. Using a
      standardized method, 25 isolates of C. neoformans and 19 of C. gattii were seeded
      in Christensen urea broth medium for urease activity detection. Approximately,
      the 50% of activity of one unit of commercial jack beans urease (A550=0.215) was
      considered as a reference to classified the Cryptococcus in two cathegories, low
      (A550<0.215) or high (A550=or>0.215) urease producers. After 72 hours of
      incubation, 76% of C. neoformans and 15.8% of C. gattii strains were high urease
      producers (p=0.016). Based on these results, the species C. neoformans appeared
      as the highest urease producer. Other virulence factors should also be
      investigated to explain C. gattii pathogenicity.

PMID- 18338925
TI  - [Multicentric and localized tineas in immunocompromised patients].
AB  - From the dermatological point of view, multifocal or multicentric tineas are
      widespread dermatophytic infections affecting two or more anatomical areas. In
      the immunosuppressed patient, these lesions are frequently atypical and the risk
      factors are not well established. The aims of this study were: to determine the
      risk factors associated to multicentric tinea in immunocompromised patients; to
      evaluate the immune response by trichophytin and candidin skin test, to determine
      the etiological agent and to quantify some serum interleukines. Thirty-six
      multicentric tinea and 37 localized tinea patients, both with immunocompromised
      factors, were included. By means of a questionnaire several risk factors were
      identified; the trichophytin and candidin skin test was evaluated after 48 hours.
      Mycological direct examination and culture were performed. The interleukins IL-2,
      IL-4, IL-10 and interferon gamma were quantified by ELISA. Statistical analysis
      was made by Chi-square, U Mann Whitney and logistic regression. In disseminated
      tinea patients a predominance of females (69%) versus localized tinea patients
      (30%) was observed. Prednisone, azathioprine and cyclophosphamide treatment was
      associated to multicentric tinea. Trichophytin was negative in all disseminated
      tinea patients and positive in only three localized tinea cases, candidin was
      positive in six and eight cases of multicentric and localized tinea respectively.
      Trichophyton rubrum was the most frequent etiological agent. No differences in
      interleukin concentrations were found. Female gender and some immunosuppressor
      treatments were associated with a high probability to develop multicentric tinea.
      In this study a defect in the cellular immune response was the possible
      explanation for the extensive reactions.

PMID- 18338926
TI  - A seed and feed model for the formation of Candida albicans biofilms under flow
      conditions using an improved modified Robbins device.
AB  - A variety of manifestations of Candida albicans infections are associated with
      the formation of biofilms on the surface of biomaterials. In order to maintain
      their niche these adherent populations need to withstand the continuous bathing
      action of physiological fluids (saliva, blood), which also provide water and
      nutrients to the fungal cells. Thus, it was the aim of this study to examine and
      further characterize the development of C. albicans biofilms under shear forces
      and a flow of replenishing nutrients, emulating the conditions that fungal cells
      would normally encounter within the host. An improved modified Robbins device
      (MRD) was designed to hold six poly methyl methacrylate (PMMA) plugs of 25 mm in
      diameter. A "seed and feed" model of biofilm formation was then implemented for
      which the apparatus was initially seeded with a C. albicans cell suspension to
      allow initial adhesion of fungal cells to the biomaterial. Following this initial
      step, sterile medium was then pumped through the MRD at a constant flow rate.
      Scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM)
      demonstrated a high degree of heterogeneity associated with the structure of
      biofilms formed under flowing conditions using the MRD. In addition, these
      biofilms displayed a complex three dimensional architecture and increased
      production of exopolymeric material.

PMID- 18338927
TI  - [Cavitary pneumonia in an AIDS patient with cryptococcosis].
AB  - Pulmonary cryptococcosis is an unusual fungal infection that is most often found
      in AIDS or in organ transplant recipients. Although in immunocompromised
      patients, cryptococcal infection often causes pulmonary infections, the diagnosis
      of lung involvement is generally difficult. The presentation of pulmonary
      cryptoccosis in HIV-infected patients appears to be more acute and severe than in
      other immunocompromised patients, probably related with the severe
      immunosuppression. Diffuse infiltrates, mediastinal and hilar lymph nodes
      enlargement are the most common radiological findings in AIDS-associated
      pulmonary cryptococcosis. Cavitation is a rare form of and includes only 10% to
      15% of all cases. Only a few case reports or studies with small number of
      patients of pulmonary cryptococcosis have been published over the past two
      decades. We report a case of an AIDS patient who developed cavitary pneumonia as
      the only clinical expression of cryptococcosis.

PMID- 18338928
TI  - [Non-dermatophytic moulds: onychomycosis in four patients infected with the human
      immunodeficiency virus].
AB  - Patients infected with human immunodeficiency virus (HIV) are a risk group for
      onychomycosis, fungal infections caused mainly by dermatophytes and yeast.
      However, non-dermatohytic moulds are becoming common agents for nail infections
      in this population of patients. We report four cases of onychomycosis caused by
      non-dermatophytic moulds (Aspergillus niger, Scytalidium hyalinum, Scytalidium
      dimidiatum and Fusarium solani) in patients infected with HIV from Recife,
      Pernambuco, Brazil. Onychomicosis by non-dermatophytic species in HIV-positive
      patients requires special attention in the clinical and the laboratory. A proper
      diagnosis is necessary to establish the specific and adequate treatment,
      preventing fungal invasion.

PMID- 18338929
TI  - Isolated lymphadenitis due to Histoplasma capsulatum diagnosed by fine-needle
      aspiration biopsy and immunohistochemistry.
AB  - In the disseminated form of histoplasmosis, isolation and further identification
      of Histoplasma capsulatum can be performed by several methods, namely, bone
      marrow aspiration, blood culture, and liver biopsy. Lymph node disease usually is
      diagnosed by excisional biopsy. Although fungal stains can identify this fungus,
      detection of specific antigens by immunohistochemistry shows a higher specificity
      and sensitivity. This approach can use the cell block method when the material is
      not sent to fungal cultures or fresh staining.

PMID- 18338930
TI  - [Paracoccidioidomycosis in a four-year-old boy].
AB  - A paracoccidioidomycosis case in a four-year old boy, with fever, lymphadenopathy
      and hepatosplenomegaly is presented. The diagnosis was confirmed by serology and
      lymph node biopsy. The patient was treated with amphotericin B. After 48 hours,
      clinical improvement and considerable adenopathies remission were observed.

PMID- 18338931
TI  - Infectious arthritis as the single manifestation of sporotrichosis: serology from
      serum and synovial fluid samples as an aid to diagnosis.
AB  - Sporotrichosis is a generally cutaneous, granulomatous, chronic and benign
      infection. Less frequently the disease may affect the joints. Articular
      involvement is usually characterized by monoarthritis in the absence of systemic
      symptoms, generally preceded by skin lesions, and frequently affects
      immunosuppressed individuals. We describe here the case of a healthy patient
      presenting knee arthritis without skin lesions, diagnosed as sporotrichosis, and
      treated with oral itraconazole. Serology used in this case was an invaluable tool
      for the diagnosis of sporotrichosis arthritis lacking skin lesions.

PMID- 18338932
TI  - [Use of kenaf fibre in the elaboration of specific substrates for Pleurotus
      ostreatus (Jacq. ex Fr.) Kummer cultivation].
AB  - In this study, the viability of the kenaf fibre use, alone or combined with
      cereal straw, vine shoots and olive mill dried waste, in the elaboration of
      specific substrates for the cultivation of Pleurotus ostreatus (Jacq. ex Fr.)
      Kummer, second mushroom in importance cultivated in Spain, is described.
      Furthermore, three different methods of preparation of the substrate have been
      considered in order to obtain selectivity for the growth and later fruiting of
      Pleurotus sporophore. As for the production parameters, the best results have
      been provided by the substrates that combined kenaf with straw and with vine
      shoots, being unfavourable the substrates based in just kenaf or combined with
      olive mill dried waste. As for the treatment applied to the materials, the
      immersion in water alone and subsequent pasteurization and thermophilic
      conditioning, together with the semi-anaerobic fermentation, has been favoured in
      front of the immersion in water with fungicide and later pasteurization.

PMID- 18338933
TI  - [Clinical cases in medical mycology. Case no. 31].

PMID- 18338934
TI  - [Clinical cases in medical mycology. Case no. 32].

PMID- 18338935
TI  - Ganglioglioma associated with cerebral cortical dysplasia: an unusual case with
      extensive leptomeningeal involvement.
AB  - Ganglioglioma is a tumor occurring in children and young adults and characterized
      by a superficial cortical location and biphasic histologic differentiation
      encompassing neuronal and glial elements. Ganglioglioma may arise anywhere
      throughout the neuraxis, including the optic nerve, brain stem, pineal gland,
      cerebellum, cerebrum, and spinal cord; however, the majority of glioneuronal
      neoplasms involve the temporal lobe. Gangliogliomas may show focal leptomeningeal
      involvement, but predominant leptomeningeal involvement by gangliogliomas is
      extremely rare; only 2 cases of ganglioglioma extensively involving the
      leptomeninges have been reported. In this report, we present an unusual case of a
      ganglioglioma predominantly present within the leptomeninges of a 15-year-old boy
      with a history of seizures. Furthermore, the cerebral cortex beneath the tumor
      showed dysplastic changes. We report a very unusual case of ganglioglioma
      involving predominantly the cerebral leptomeninges and associated with adjacent
      cerebral cortical dysplasia. Histologic characteristics and diagnostic pitfalls
      are discussed.

PMID- 18338937
TI  - Recurrent nested stromal epithelial tumor of the liver with extrahepatic
      metastasis: case report and review of literature.
AB  - Nested stromal epithelial tumor is a recently described primary neoplasm of the
      liver. This tumor is characterized by well-demarcated nests of spindle and
      epithelioid cells with occasional calcification and bone formation. An
      association between these tumors and Cushing syndrome has been described. Herein
      we report a case of a recurrent nested stromal epithelial tumor of the liver in a
      17-year-old female with aggressive clinical behavior and an extrahepatic lymph
      node metastasis. Also, we provide the first detailed clinical, histologic,
      immunohistochemical, and cytogenetic comparison of the original and recurrent
      tumors. Initially, the patient presented with Cushingoid symptoms and epigastric
      pain, radiating to her back. A computed tomographic (CT) scan revealed a large
      lesion in the liver. After a partial hepatectomy, the Cushingoid features were
      resolved. A year later, a CT scan revealed multiple lesions within the liver, and
      positron emission tomographic/CT imaging showed a hypermetabolic lymph node. The
      patient underwent a cadaveric liver transplant. Histologically, both the original
      and recurrent tumors had similar characteristics, with different
      immunoreactivity, correlating with the absence of systemic hormonal symptoms.
      Electron microscopy of the original neoplasm revealed an abundance of rough
      cytoplasmic reticulum and mitochondria. No evidence of endocrine differentiation
      was found. Cytogenetics of the primary tumor was complex with an abnormal
      hypotriploid karyotype. Our data indicate that patients with nested stromal
      epithelial tumor of the liver must be carefully followed with imaging to detect
      hepatic recurrence and extrahepatic metastases.

PMID- 18338938
TI  - The problems and promise of central pathology review.

PMID- 18338942
TI  - Laboratory abnormalities among HIV-1-infected pregnant women receiving
      antiretrovirals in Latin America and the Caribbean.

PMID- 18338943
TI  - Health and health behaviors in HIV-infected jail inmates, 1999 and 2005.
AB  - Incarcerated HIV-infected persons in San Francisco have benefited from intensive
      case management in jail and postrelease, which includes but is not focused on
      interventions to prevent transmission. In this population of predominately
      injection drug users (IDUs), we had the opportunity to examine interview data
      from 1999 and 2005 that included health characteristics and risk factors. Those
      in 2005 were less likely to be satisfied with social support and less likely to
      be partnered; more likely to have some form of health insurance. On average,
      health was perceived in both periods to be better the longer the person had been
      in jail. Injection drug use was reported lower in 2005, but a subset of nearly a
      quarter in each survey time period reported sharing needles. Persons in 2005 were
      less likely to report they always used condoms as compared to those in 1999 (odds
      ratio 0.26, 95% confidence interval 0.12-0.59, p = 0.001). While there were
      differences in study design and methodology, this comparison demonstrated overall
      similarities in characteristics of HIV-infected inmates. Findings echo those of
      others, in other populations of HIV-infected persons. Reasons could include HIV
      prevention fatigue or decay in effectiveness of prevention messages. Despite an
      established program for case management and links to services, renewed efforts
      are needed to maintain effectiveness of prevention strategies to this high-risk
      population.

PMID- 18338944
TI  - Trial studies extended release Viramune.

PMID- 18338945
TI  - Acyclovir does not reduce risk of HIV infection.

PMID- 18338946
TI  - IFN-beta-dependent inhibition of tumor growth by the vascular disrupting agent
      5,6-dimethylxanthenone-4-acetic acid (DMXAA).
AB  - By attacking established tumor vasculature, vascular disrupting agents (VDAs)
      represent an alternative approach to the treatment of cancer. One such VDA, 5,6
      dimethylxanthenone-4-acetic acid (DMXAA), is scheduled for phase III trials for
      prostate and lung cancer in combination with conventional chemotherapies. In this
      work, we identify interferon-beta (IFN-beta) as a central mediator in the host's
      response to DMXAA. In mice bearing Lewis lung adenocarcinomas, a single
      intraperitoneal dose of DMXAA was shown to effect a highly significant reduction
      in tumor growth rate in wild-type mice that was not seen in IFN-beta-null mice.
      Moreover, intratumoral cytokine expression was shown to be dependent on host
      derived IFN-beta, as DMXAA-treated IFN-beta-null mice demonstrated a lack of
      induction of not only IFN-beta but also the antiangiogenic cytokine, IP-10, in
      excised tumor tissue. These results support the conclusion that DMXAA derives its
      potent anticancer properties in part through elicitation of IFN-beta expression
      by host-derived elements.

PMID- 18338947
TI  - Multiple sclerosis and hepatitis C virus infection are associated with single
      nucleotide polymorphisms in interferon pathway genes.
AB  - We have studied 35 single nucleotide polymorphisms (SNPs) in the interferon (IFN)
      pathway to determine their contribution to multiple sclerosis (MS) and hepatitis
      C virus (HCV) infection. A total of 182 patients with MS, 103 patients with
      chronic hepatitis C, and 118 control subjects were enrolled in the study. Of the
      35 SNPs studied, 3 were in IFN-alpha receptor (IFNAR-1), 10 in IFN-alpha/beta
      receptor (IFNAR-2), 9 in Stat1, 5 in Stat2, and 8 in IFN regulatory factor-1 (IRF
      1). Compared to controls, Stat1 gene polymorphisms were significantly more
      frequent in MS patients (rs# 2066802 OR = 7.46, 95% CI = 2.22-25.10; rs# 1547550
      OR = 1.69, 95% CI = 1.01-2.81) and in HCV patients (rs# 2066802 OR = 5.95, 95% CI
      = 1.55-22.81; rs# 1547550 OR = 2.30, 95% CI = 1.24-4.24). Also one IRF-1 gene SNP
      was associated with MS (rs# 2070721 OR = 2.05, 95% CI = 1.03-4.09), and four IRF
      1 gene SNPs were associated with HCV infection (rs# 2070721 OR = 2.59, 95% CI =
      1.23-5.43; rs# 2070723 OR = 4.8, 95% CI = 1.26-18.20; rs# 2070728 OR = 9.81, 95%
      CI = 1.21-79.4; rs# 2070729 OR = 3.6, 95% CI = 1.23-10.48; rs# 839 OR = 4.67,
      95%CI = 1.29-16.87). Characteristic nucleotide combinations on single chromosomes
      (haplotype) generated block structures, including SNPs, that differed between
      patients and controls. Using a permutation test to detect differences in
      haplotype distribution between groups, the CCATTGA and the CCGAA haplotypes in
      the IRF-1 gene were more frequent in MS (p = 0.03) and in HCV patients (p =
      0.001) than in controls. In conclusion, our data show that genetic variants in
      the IRF-1 and Stat1 genes of the IFN pathway are associated with MS and HCV
      infection.

PMID- 18338948
TI  - Natural killer cells, glutathione, cytokines, and innate immunity against
      Mycobacterium tuberculosis.
AB  - It is becoming increasingly apparent that natural killer (NK) cells play a
      crucial role in innate defense mechanisms against Mycobacterium tuberculosis
      infection. Furthermore, NK cell functions are dependent on adequate levels of
      glutathione. In this study, we examined whether the NK cell-mediated growth
      control of intracellular M. tuberculosis is dependent on adequate levels of
      glutathione. We investigated the effects of glutathione both alone and in
      combination with interleukin-2 (IL-2) or IL-12 or both in modulating NK cell
      functions, such as cytolytic activity, activating receptor expression, induction
      of apoptosis, and cytokine synthesis. Our results strongly indicate that
      glutathione in combination with IL-2+IL-12 augments NK cell functions, leading to
      control M. tuberculosis infection.

PMID- 18338949
TI  - Cigarette smoke suppresses type I interferon-mediated antiviral immunity in lung
      fibroblast and epithelial cells.
AB  - The objective of this study was to investigate the impact of cigarette smoke on
      innate antiviral defense mechanisms; specifically, we examined the effects of
      cigarette smoke on the induction of type I interferon (IFN). We observed a dose
      dependent decrease in the ability of human lung fibroblast and epithelial cells
      to elicit an antiviral response against a viral double-strand RNA (dsRNA) mimic,
      polyI:C, in the presence of cigarette smoke-conditioned medium (SCM).
      Mechanistically, SCM decreases the expression of IFN-stimulated gene 15 (ISG15)
      and IFN regulatory factor-7 (IRF-7) transcripts and suppresses the nuclear
      translocation of key transcription factors, nuclear factor-kappaB (NF-kappaB) and
      IRF-3, after polyI:C stimulation. Furthermore, we provide evidence that the
      intercellular defense strategy against viral infection is also impaired. We
      observed a decrease in the ability of fibroblasts to elicit an antiviral state in
      response to IFN-beta stimulation. This was associated with decreased nuclear
      translocation of phosphorylated Stat1 in response to IFN-beta treatment. The
      effects elicited by SCM are reversible and are almost entirely abrogated in the
      presence of an antioxidant, such as glutathione. Our findings suggest that
      cigarette smoke affects the immediate-early, inductive, and amplification phases
      of the type I IFN response.

PMID- 18338950
TI  - Decreased type I interferon receptor-soluble isoform in antiretroviral-treated
      HIV-positive children.
AB  - We developed a real-time PCR assay to simultaneously measure the mRNA level of
      type I interferon (IFN) receptor (IFNAR) components in peripheral blood cells of
      children with chronic immune stimulation due to HIV infection. All patients were
      undergoing antiretroviral therapy and were divided into two groups on the basis
      of the induction of MxA mRNA, a marker of type I IFN bioactivity. We found that
      IFNAR-2 subunit mRNA was higher than that of the IFNAR-1 subunit, that the mRNA
      for the IFNAR-2.2 functional isoform was more expressed than that for the
      truncated IFNAR-2.1 isoform, and both were much more represented than that of the
      IFNAR-2.3 soluble isoform. We also demonstrated that soluble isoform mRNA was
      significantly diminished in the subgroup of patients with MxA mRNA below the
      cutoff value (determined as the 99th percentile of MxA measured in healthy
      controls). These results suggest that downregulation of the soluble receptor
      isoform, which would not compete with the functional isoform for binding to the
      target cytokine, would give type I IFN, eventually induced in these patients in
      the case of viral reactivation, the opportunity to promptly exert its antiviral
      activity.

PMID- 18338951
TI  - The antibacterial chemokine MIG/CXCL9 is constitutively expressed in epithelial
      cells of the male urogenital tract and is present in seminal plasma.
AB  - The integrity of the urogenital tract against potentially invasive pathogens is
      important for the health of the individual, fertilization, and continuance of
      species. Antibiotic peptides with broad antimicrobial activity, among them
      chemokines, are part of the innate immune system. We investigated the presence of
      the antibacterial interferon (IFN)-dependent CXC chemokines, MIG/CXCL9, IP
      10/CXCL10, and I-TAC/CXCL11, in the human male reproductive system. MIG/CXCL9 was
      detected at 25.0 nM (range 8.1-40.6 nM; n = 14), whereas IP-10/CXCL10 and I
      TAC/CXCL11 were detected at lower levels (mean 1.8 nM, range 0.3-5.8 nM and mean
      0.6, 0.2-1.6 nM, respectively) in seminal plasma of fertile donors. The levels of
      MIG/CXCL9 are more than 300-fold higher than those previously reported in blood
      plasma. In vasectomized donors, significantly lower levels of MIG/CXCL9 (mean
      14.7 nM, range 6.6-21.8) were found, suggesting that the testis and epididymis,
      in addition to the prostate, significantly contribute to the MIG/CXCL9 content of
      seminal plasma. Strong expression of MIG/CXCL9 was found in the epithelium of
      testis, epididymis, and prostate, as detected by immunohistochemistry. MIG/CXCL9
      at concentrations in the order of those found in seminal plasma possessed
      antibacterial activity against the urogenital pathogen Neisseria gonorrhoeae. The
      relatively high levels of MIG/CXCL9 in seminal plasma point to roles for this
      chemokine in both host defense of the male urogenital tract and during
      fertilization.

PMID- 18338953
TI  - Reprogramming, regeneration, and the stem cell niche: meeting report on the 4th
      International Meeting of the Stem Cell Network North Rhine Westphalia.

PMID- 18338954
TI  - Embryonic stem cells contribute to mouse chimeras in the absence of detectable
      cell fusion.
AB  - Embryonic stem (ES) cells are capable of differentiating into all embryonic and
      adult cell types following mouse chimera production. Although injection of
      diploid ES cells into tetraploid blastocysts suggests that tetraploid cells have
      a selective disadvantage in the developing embryo, tetraploid hybrid cells,
      formed by cell fusion between ES cells and somatic cells, have been reported to
      contribute to mouse chimeras. In addition, other examples of apparent stem cell
      plasticity have recently been shown to be the result of cell fusion. Here we
      investigate whether ES cells contribute to mouse chimeras through a cell fusion
      mechanism. Fluorescence in situ hybridization (FISH) analysis for X and Y
      chromosomes was performed on dissociated tissues from embryonic, neonatal, and
      adult wild-type, and chimeric mice to follow the ploidy distributions of cells
      from various tissues. FISH analysis showed that the ploidy distributions in
      dissociated tissues, notably the tetraploid cell number, did not differ between
      chimeric and wild-type tissues. To address the possibility that early cell fusion
      events are hidden by subsequent reductive divisions or other changes in cell
      ploidy, we injected Z/EG (lacZ/EGFP) ES cells into ACTB-cre blastocysts.
      Recombination can only occur as the result of cell fusion, and the recombined
      allele should persist through any subsequent changes in cell ploidy. We did not
      detect evidence of fusion in embryonic chimeras either by direct fluorescence
      microscopy for GFP or by PCR amplification of the recombined Z/EG locus on
      genomic DNA from ACTB-cre::Z/EG chimeric embryos. Our results argue strongly
      against cell fusion as a mechanism by which ES cells contribute to chimeras.

PMID- 18338955
TI  - Effect of tamsulosin in preventing ureteral stent-related morbidity: a
      prospective study.
AB  - PURPOSE: We conducted a randomized study to evaluate the effect of tamsulosin in
      improving symptoms and quality of life (QoL) in patients with indwelling double
      pigtail ureteral stents, using both generic and specific questionnaires.
      MATERIALS AND METHODS: We prospectively enrolled 75 patients (29 men, 46 women;
      mean age, 42.3 years), who underwent ureteral stent positioning and were assigned
      to one of two study groups. In group A (n = 38), patients were discharged with a
      prescription for tamsulosin, 0.4 mg once daily. In group B (n = 37), patients
      received no alpha(1)-blocker (control group). RESULTS: One week after stent
      placement (visit week 1 [W1]), analysis of the ureteral stent symptoms
      questionnaire showed a significant worsening of urinary symptoms (13.1 v 26.4, P
      = 0.008) and pain (4.1 v 21.6, P = 0.002) in patients not receiving tamsulosin.
      There was also a significant difference in the mean visual analog score (VAS) of
      health scale between the two groups (P < 0.001) compared with the result obtained
      at the W4 evaluation (visit). The proportion of patients reporting level 2 or 3
      for the pain/discomfort domain in the QoL questionnaire from W4 to W1 varied
      between the two groups in a highly statistically significant manner (P = 0.006).
      CONCLUSIONS: Our findings indicate that administration of tamsulosin has a
      positive effect on stent-related urinary symptoms and QoL. Further clinical
      research in this area is warranted to better define the role of alpha(1)-blockers
      in current clinical practice.

PMID- 18338956
TI  - Transurethral endoscopy technique with a ureteroscope for diagnosis and
      management of seminal tracts disorders: a new approach.
AB  - PURPOSE: To apply a transurethral endoscopic technique for examining and managing
      suspicious distal seminal tracts disorders with a ureteroscope. PATIENTS AND
      METHODS: Sixteen patients with distal seminal tracts disorders underwent
      transurethral endoscopy through the distal seminal tracts using a semirigid
      ureteroscope. Of the 16 patients, 6 had suspected hemospermia, 4 spermatocele,
      and 6 male infertility. RESULTS: The ejaculatory duct, seminal vesicle, and
      ampulla of the vas deferens were observed under direct vision with the
      ureteroscope. The vas deferens was investigated by cannulation with a guidewire
      or an epidural anesthesia catheter. Four patients received a diagnosis of
      spermatocele, four seminal vesiculitis, and three vas deferens obstruction. All
      patients received appropriate treatment. The remaining five patients had no
      anatomic disorders. All patients received careful postoperative observation and
      treatment, and were monitored for at least 3 months. Three patients had
      postoperative discomfort in the perineal region. There were no further
      complications. CONCLUSIONS: This new technique with the ureteroscope enables
      diagnosis and management of distal seminal tracts disorders through the normal
      anatomic tract. This endoscopic technique can be performed easily with minimal
      complications.

PMID- 18338957
TI  - Initial experience with robot-assisted minimally-invasive nephroureterectomy.
AB  - PURPOSE: Various techniques have been described for laparoscopic
      nephroureterectomy. We reviewed our initial experience of laparoscopic
      nephroureterectomy with robot-assisted extravesical excision of the distal ureter
      and bladder cuff. MATERIALS AND METHODS: Nine consecutive patients aged 43 to 83
      years underwent laparoscopic nephroureterectomy for transitional cell carcinoma
      (TCC) between August 2005 and March 2007. The first five patients were
      repositioned after laparoscopic nephrectomy from flank to lithotomy position to
      dock the robot for excision of the distal ureter and bladder cuff by a single
      surgeon. In contrast, the last four patients remained in flank position
      throughout the entire procedure, with the robot docked in flank position
      following laparoscopic nephrectomy. A two-layer closure re-approximated the
      cystotomy and a urethral catheter was left in place for a mean of 5 days.
      RESULTS: Eight men and one woman with a mean age of 64.2 years and mean body mass
      index (BMI) of 28.4 kg/m(2) underwent flexible cystoscopy and laparoscopic
      nephroureterectomy for five right-sided and four left-sided tumors. Mean
      operative time was 303 minutes (range 210-430 minutes), estimated blood loss was
      211 mL (range 50-700 mL), and mean length of hospital stay was 2.3 days.
      Pathologic staging revealed T(3) for five (55.6%), T(a) for two (22.2%),
      carcinoma in situ (CIS) for two (22.2%) patients, and high-grade disease for
      seven (77.8%) patients. With a mean follow-up of 16.2 months (range 4.3-24.3
      months), three patients with a history of bladder cancer have experienced
      recurrence in the bladder, and one of the three has also developed metastatic
      disease. CONCLUSIONS: Laparoscopic nephroureterectomy with robot-assisted
      extravesical excision of the distal ureter and bladder cuff appears to be a
      feasible alternative for patients with TCC of the upper urinary tract.

PMID- 18338958
TI  - Safety and efficacy of percutaneous nephrolithotomy in the pediatric population.
AB  - PURPOSE: We reviewed our experience with percutaneous nephrolithotomy (PCNL) in
      patients in the pediatric age group and compared its efficacy and safety over a 5
      year period. PATIENTS AND METHODS: We studied retrospectively and prospectively
      31 patients who were treated with PCNL for renal stones larger than 1.5 cm.
      Variables assessed were stone bulk, size, location, and type. Metabolic and
      anatomic factors were also assessed. PCNL punctures and number of tracts were
      recorded. Clearance with PCNL and ancillary procedures was recorded. RESULTS:
      There were 31 renal units. Mean age of the patients was 9.6 years (range 1.5-15
      years). Fifteen (48.4%) patients had single calculi; eight (25.8%) patients had
      staghorn calculi. Lower-pole access was the preferred route of entry, and upper
      pole access was used only when necessary. We used a 22F nephroscope for the
      procedure. We dilated the tract to 30F in the majority of patients, but limited
      dilation to 24F when appropriate. If needed, we used a ureteroscope. Complete
      clearance was achieved in 83.9% of patients after PCNL and in 90.32% of patients
      after dual therapy (PCNL + shockwave lithotripsy). Average hemoglobin drop was
      less than 1 g/dl. Factors responsible were the size of the tract (larger than
      24F) and the number of tracts. Six patients were treated for an anatomic
      abnormality. A metabolic abnormality was diagnosed in three patients. CONCLUSION:
      PCNL is effective in children, with a clearance rate of 83% and, with dual
      therapy, more than 90%. We recommend that tract dilation be restricted to 24F or
      smaller whenever possible. Approximately 40% of patients had either an anatomic
      or metabolic abnormality.

PMID- 18338959
TI  - Force-dependent development of neuropathic central pain and time-related
      CCL2/CCR2 expression after graded spinal cord contusion injuries of the rat.
AB  - Spinal cord injury (SCI) often results in intractable chronic central pain
      syndromes. Recently chemokines such as CCL2 were identified as possible key
      integrators of neuropathic pain and inflammation after peripheral nerve lesion.
      The focus of the current study was the investigation of time-dependent CCL2 and
      CCR2 expression in relation to central neuropathic pain development after spinal
      cord impact lesions of 100, 150, or 200 kdyn force on spinal cord level T9 in
      adult rats. Below-level pain was monitored with weekly sensory testing for 42
      days after SCI. In parallel expression of CCL2/CCR2 on cervical, thoracic, and
      lumbar levels was investigated by real-time reverse transcriptase-polymerase
      chain reaction (RT-PCR) and immunohistochemistry early (7 days [7d]),
      intermediate (15d), and late (42d) after lesion. Cellular source and anatomical
      pain related expression was determined by double-immunohistochemistry. Force
      defined SCI led to acute mechanical hypersensitivity in all lesion groups, and to
      persistent below-level pain in severely injured animals. While in the early post
      operative time course, CCL2 and CCR2 were expressed in astroglia and granulocytes
      only on level T9; there was additional astroglial CCL2 expression in dorsal
      columns and dorsal horns above and below T9 of severely injured animals 42d after
      lesion. In dorsal horns (level L3-L5) of animals exhibiting chronic below-level
      pain CCL2 was co-expressed with transmitters and receptors that are involved in
      nociceptive processing like calcitonin gene-related peptide (CGRP), Substance-P,
      vanilloid-receptor-1, and its activated phosphorylated form. These data
      demonstrate lesion grade dependence of below-level pain development and suggest
      chemokines as potential candidates for integrating inflammation and central
      neuropathic pain after SCI.

PMID- 18338960
TI  - The relationship of post-traumatic stress disorder and depression to
      antiretroviral medication adherence in persons with HIV.
AB  - In HIV/AIDS, symptoms of depression or post-traumatic stress may interfere with
      important self-care behaviors such as the ability to adhere to one's medical
      treatment regimen. However, these problems may frequently go undetected in HIV
      care settings. The present study used brief self-report screening measures of
      depression and post-traumatic stress disorder (PTSD) in the HIV/AIDS care
      settings to examine (1) frequency of positive screens for these diagnoses; (2)
      the degree to which those with a positive screen were prescribed antidepressant
      treatment; and (3) the association of continuous PTSD and depression symptom
      scores, and categorical (screening positive or negative) PTSD and depression
      screening status, to each other and to ART adherence as assessed by the
      Medication Event Monitoring System, regardless of antidepressant treatment.
      Participants were 164 HIV-infected individuals who took part in a multisite
      adherence intervention study in HIV treatment settings in Massachusetts.
      Available data from 5 time points was used, yielding 444 data points.
      Participants screened positive for PTSD at 20% of visits, and depression at 22%
      of visits. At visits when participants screened positive for both depression and
      PTSD, 53.6% of the time they were on an antidepressant. Those who screened
      positive for PTSD were more likely to also screen positive for depression. In
      multiple regression analyses that included both continuous and dichotomous PTSD
      and depression and controlled for shared variance due to clustering of multiple
      observations, only depression contributed significant unique variance, suggesting
      the primary role of depression and the secondary role of PTSD in poor adherence
      in individuals with HIV.

PMID- 18338961
TI  - Influence of prior antiretroviral experience on adherence and responses to new
      highly active antiretroviral therapy regimens.
AB  - The impact of prior antiretroviral experience on adherence and clinical outcomes
      in patients initiating a new highly active antiretroviral therapy (HAART) regimen
      is not well defined. We performed an observational cohort analysis of
      antiretroviral-experienced or -naive HIV-infected patients prescribed a new HAART
      regimen (3538 patients) and enrolled in Kaiser Permanente Northern California
      from 1997 through 2002. Outcomes evaluated were HAART adherence and changes in
      HIV RNA level and CD4 T-cell counts over 12 and 24 months. The antiretroviral
      naive group had a significantly greater odds of achieving >/=95% adherence to the
      HAART regimen over 12 months (adjusted odds ratio [OR] = 1.88, p < 0.001) and
      over 24 months (OR = 1.66, p < 0.001). The odds of achieving HIV RNA levels below
      limits of quantification also was higher among patients who were antiretroviral
      naive; over 24 months OR = 6.88, p < 0.001. Adjusted change in CD4 T-cell count
      was also greater among naive patients over 24 months (+67 cells/muL, p < 0.001),
      compared to antiretroviral-experienced patients. Years of antiretroviral
      experience did not affect adherence or any outcome measure. Adjusting for HAART
      adherence did not significantly affect HIV RNA results but did lessen CD4 T-cell
      count differences between antiretroviral-naive and -experienced patients. Thus,
      antiretroviral naive patients have improved HAART adherence, HIV RNA control, and
      CD4 T-cell count increases compared to antiretroviral-experienced patients
      regardless of years of antiretroviral experience. These findings should help
      direct HAART adherence efforts in HIV care clinics.

PMID- 18338962
TI  - Sex differences in systolic heart failure in the elderly: the prognostic
      importance of left ventricular mass in women.
AB  - HYPOTHESIS: We investigated the hypothesis that there are prognostic differences
      in the importance of left ventricular (LV) mass and function between male and
      female patients hospitalized with heart failure. METHODS: Patients > or =60 years
      old hospitalized with New York Heart Association class II-IV heart failure and LV
      systolic dysfunction were prospectively followed for > or =18 months. At study
      start, a physical examination and echocardiography were performed, and blood
      chemistry samples were obtained. RESULTS: Of 158 patients, 66 (42%) women were
      included and were followed for a mean of 3.1 years. The women were older (77 +/-
      7 vs. 74 +/- 7 years, p < 0.01) and had lower mortality (24% vs. 43%, p < 0.05)
      than the men. No gender differences in etiology or medication were found. LV mass
      index (LVMI 132 +/- 42 vs. 156 +/- 21 g/m(2), p < 0.01) was lower in women.
      Mortality in women was related to lower LV ejection fraction, larger LV volumes,
      and higher LVMI (all p < 0.05). In multivariate analysis, LVMI was the strongest
      independent mortality predictor in women (adjusted hazard ratio [HR] LMVI >125
      g/m(2) 7.4 [1.5-35.5], p = 0.01), whereas this association was not found in men.
      CONCLUSIONS: In patients hospitalized with systolic heart failure, women had
      lower mortality than men. In women, an increased LVMI was a stronger predictor of
      mortality than traditional measures of LV size and function. LVMI should be
      considered for assessment of prognosis in women with heart failure.

PMID- 18338963
TI  - Effectiveness of a lifestyle physical activity intervention in a women's
      organization.
AB  - OBJECTIVE: The objective of the present study was to evaluate the effectiveness
      of a minimal contact physical activity intervention that was maximally integrated
      into the existing structures of a women's organization. METHODS: The intervention
      included one group meeting, a self-help booklet, and five monthly reminder
      letters and was implemented in four units of a rural women's organization. Two
      other units served as control group. Pretest and posttest measurements were
      completed by 81 women in the intervention group and 88 in the control group.
      Physical activity was assessed at baseline and at 6 months with accelerometers
      and the International Physical Activity Questionnaire (IPAQ). RESULTS: There was
      a significant interaction between time and group for the total accelerometer
      activity counts (p = 0.007). Total activity counts increased in the intervention
      group, whereas there was a decrease in the control group. No significant results
      were found with the IPAQ. CONCLUSIONS: An intervention in a women's organization
      was effective in increasing the objectively measured physical activity levels of
      its members. These results indicate that women's organizations can be valuable
      settings for physical activity promotion programs. The minimal number of contact
      hours and the use of existing structures and communication channels are important
      strengths for later implementation.

PMID- 18338964
TI  - Gender bias in the clinical management of women with angina: another look at the
      Yentl syndrome.
AB  - BACKGROUND: Woman with heart disease may receive lower levels of clinical care
      than men. We assessed whether the Yentl syndrome (women receive equivalent care
      to men only when they demonstrate that they are like men by having a heart
      attack) operates in the management of angina pectoris in primary care. METHODS:
      The study design is a cross-sectional survey of 1162 angina patients (552 women)
      managed in eight sentinel centers serving 15% of the population of Liverpool.
      Data were extracted by specially trained data managers. Analysis included
      directly age-standardized proportions and male/female adjusted odds ratios (AOR),
      adjusted for age, disease duration, physician consultation rate, and age at
      diagnosis. RESULTS: All aspects of care were higher for men with angina-previous
      myocardial infarction (MI) than for women with angina-previous MI. Risk factor
      recording was an absolute 8% higher (95% CI 1%-17%), secondary prevention 9%
      higher (95% CI 1%-17%), cardiac investigation 10% higher (95% CI 1%-20%), and
      revascularization 13% higher (95% CI 4%-22%). Men with angina-previous MI
      consistently received the highest level and women with angina the lowest level of
      risk factor recording (AOR 1.79, 95% CI 1.21-2.66), secondary prevention (AOR
      2.24, 95% CI 1.47-3.40), cardiac investigation (AOR 2.21, 95% CI 1.56-3.13), and
      revascularization (AOR 4.67, 95% CI 3.03-7.18). The provision of care to men with
      angina alone and women with angina-previous MI fell between these two extremes.
      CONCLUSIONS: A gender-based clinical hierarchy operates in the clinical
      management of angina pectoris in primary care. The Yentl syndrome did not apply,
      however, as women with angina received less intensive clinical care than similar
      men irrespective of prior MI.

PMID- 18338965
TI  - Sex differences in treatment patterns of six chronic diseases: an analysis from
      the German statutory health insurance.
AB  - OBJECTIVE: The goal of this study was to investigate gender-specific differences
      in prevalence, healthcare costs, and treatment patterns in the German Statutory
      Health Insurance (SHI). METHODS: The study analyzed administrative claims data of
      over 26 million insured with respect to prevalence and cost of illness of six
      chronic diseases. Insured were identified using the ATC code for medication
      prescription and ICD-9 code for diagnosis. The influences of gender, age, and
      comorbidity on cost differences were analyzed via multivariate regression
      analysis. RESULTS: Adjusted for age and comorbidity, gender had a significant
      influence on both hospital and medication spending. Hospital costs on average
      were 17.1% (95% CI 14.1; 20.2) higher for men compared with women. Medication
      spending for men exceeded that for women on average by 13.8% (95% CI 10.9; 16.7).
      The diagnoses with the highest prevalence were hypertension and heart failure.
      Women had a higher prevalence of diabetes, coronary artery disease (CAD), heart
      failure, and hypertension. Medication costs were higher for men in three of five
      diagnoses and comparable for two diagnoses (diabetes and asthma). Women received
      more medication prescriptions than men, but on average prescriptions for men were
      14%-26% more expensive than prescriptions for women. Regarding treatment patterns
      men were treated with different drug classes in cardiovascular disease (CVD)
      compared with women. Total medication spending stratified by diagnosis was
      highest for diabetes. CONCLUSIONS: Gender differences for costs and prescribing
      patterns for chronic diseases vary disease specifically, but generally men had
      higher inpatient costs and more expensive medication prescriptions, whereas women
      had higher numbers of prescriptions.

PMID- 18338966
TI  - A comparative study of the effects of laser photobiomodulation on the healing of
      third-degree burns: a histological study in rats.
AB  - OBJECTIVE: The aim of this investigation was to compare by light microscopy the
      effects of laser photobiomodulation at wavelengths of 660 and 780 nm on third
      degree burns in Wistar rats. BACKGROUND DATA: Burns are severe injuries that
      result in the loss of fluid and destruction of tissue, infection, and shock that
      may result in death. Laser energy has been suggested as an effective method to
      improve wound healing. MATERIALS AND METHODS: Fifty-five animals were used in
      this study. A third-degree burn measuring 1.5 x 1.5 cm was created on the dorsum
      of each animal. The animals were divided into three subgroups according the type
      of laser photobiomodulation they received (wavelength of 660 or 780 nm, 35 mW,
      theta = 2 mm, and 20 J/cm2). In the animals receiving treatment, it was begun
      immediately post-burn at four points around the burn (5 J/cm2) and repeated at 24
      h intervals for 21 d. The animals were humanely killed after 3, 5, 7, 14, and 21
      d by an intraperitoneal overdose of general anesthetic. The specimens were
      routinely cut and stained, and then were analyzed by light microscopy. RESULTS:
      The results showed more deposition of collagen fibers, larger amounts of
      granulation tissue, less edema, a more vigorous inflammatory reaction, and
      increased revascularization on all laser-treated animals. These features were
      more evident at early stages when the 660-nm laser was used, and were more
      evident throughout the experimental period for the animals receiving 780-nm laser
      therapy. CONCLUSION: We concluded that laser photobiomodulation using both
      wavelengths improved healing of third-degree burns on Wistar rats.

PMID- 18338967
TI  - Nano-hardness of adhesive interface between Er:YAG laser-irradiated dentin and 4
      META/MMA-TBB resin.
AB  - OBJECTIVE: The purpose of this study was to evaluate the hardness of the adhesive
      interface between resin and Er:YAG laser-irradiated bovine dentin by nano
      indentation. BACKGROUND DATA: It has been reported that laser output energy and
      pulse repetition rate affect the tensile bond strength in Er:YAG laser-irradiated
      dentin. MATERIALS AND METHODS: Three laser settings were evaluated at the same
      total energy level (approximately 1.0 W): 100 mJ/pulse-10 pps (100-10), 50
      mJ/pulse-20 pps (50-20), and 33 mJ/pulse-30 pps (33-30). Laser-irradiated dentin
      in each group was conditioned with 10% citric acid solution containing 3% ferric
      chloride for 15 sec, rinsed with distilled water for 30 sec, and bonded to PMMA
      rods with 4-META/MMA-TBB resin. The bonded specimens were sectioned vertically,
      embedded in epoxy resin, and their nano-hardness measured. A non-irradiated
      control group was also investigated. RESULTS: The adhesive resin interface in the
      controls showed the lowest level of hardness, which gradually increased from the
      top of the hybrid layer (0 microm) through the bottom of the hybrid layer (5
      microm) and into the underlying dentin ( approximately 10 microm). Significant
      differences in hardness were observed between the 5 microm point in the controls,
      the 10 microm and 15 microm points in the 100-10 group, and the 10 microm point
      in the 50-20 and 33-30 groups. CONCLUSION: The results suggest that laser
      settings affect hybrid layer thickness, even when the total energy level is
      constant.

PMID- 18338968
TI  - Vestibular system: the many facets of a multimodal sense.
AB  - Elegant sensory structures in the inner ear have evolved to measure head motion.
      These vestibular receptors consist of highly conserved semicircular canals and
      otolith organs. Unlike other senses, vestibular information in the central
      nervous system becomes immediately multisensory and multimodal. There is no
      overt, readily recognizable conscious sensation from these organs, yet vestibular
      signals contribute to a surprising range of brain functions, from the most
      automatic reflexes to spatial perception and motor coordination. Critical to
      these diverse, multimodal functions are multiple computationally intriguing
      levels of processing. For example, the need for multisensory integration
      necessitates vestibular representations in multiple reference frames.
      Proprioceptive-vestibular interactions, coupled with corollary discharge of a
      motor plan, allow the brain to distinguish actively generated from passive head
      movements. Finally, nonlinear interactions between otolith and canal signals
      allow the vestibular system to function as an inertial sensor and contribute
      critically to both navigation and spatial orientation.

PMID- 18338973
TI  - Molecular spectroscopy: some personal reminiscences.

PMID- 18338974
TI  - Atmospheric ozone.

PMID- 18338975
TI  - From high-resolution spectroscopy to chemical reactions.

PMID- 18338976
TI  - The Way it Was.

PMID- 18338977
TI  - Dielectrics in physical chemistry.

PMID- 18338978
TI  - [SEN Guidelines. Recommendations of the Spanish Society of Nephrology for
      managing bone-mineral metabolic alterations in chronic renal disease patients].

PMID- 18338979
TI  - Using computational fluid dynamics to characterize and improve bioreactor
      performance.
AB  - CFD (computational fluid dynamics) has been used to model upstream bioprocessing
      steps such as fermentation and homogenization. The focus of these studies has
      oftentimes been to characterize single-phase (liquid) flow and hydrodynamic
      shear. In the actual bioprocessing operations, however, there are at least two
      phases (cells and liquid) present. In the bioreactor, the gas bubbles constitute
      a third phase. More recent CFD models have considered the momentum and mass
      transfer that occurs between the phases. This review summarizes studies from the
      biochemical and biomedical literature relating to the use of CFD to model the
      performance of a variety of bioreactor types. Particular emphasis will be placed
      on describing current methods for handling multi-phase flow involving animal
      cells and/or gas bubbles.

PMID- 18338980
TI  - Both aerobic endurance and strength training programmes improve cardiovascular
      health in obese adults.
AB  - Regular exercise training is recognized as a powerful tool to improve work
      capacity, endothelial function and the cardiovascular risk profile in obesity,
      but it is unknown which of high-intensity aerobic exercise, moderate-intensity
      aerobic exercise or strength training is the optimal mode of exercise. In the
      present study, a total of 40 subjects were randomized to high-intensity interval
      aerobic training, continuous moderate-intensity aerobic training or maximal
      strength training programmes for 12 weeks, three times/week. The high-intensity
      group performed aerobic interval walking/running at 85-95% of maximal heart rate,
      whereas the moderate-intensity group exercised continuously at 60-70% of maximal
      heart rate; protocols were isocaloric. The strength training group performed
      'high-intensity' leg press, abdominal and back strength training. Maximal oxygen
      uptake and endothelial function improved in all groups; the greatest improvement
      was observed after high-intensity training, and an equal improvement was observed
      after moderate-intensity aerobic training and strength training. High-intensity
      aerobic training and strength training were associated with increased PGC-1alpha
      (peroxisome-proliferator-activated receptor gamma co-activator 1alpha) levels and
      improved Ca(2+) transport in the skeletal muscle, whereas only strength training
      improved antioxidant status. Both strength training and moderate-intensity
      aerobic training decreased oxidized LDL (low-density lipoprotein) levels. Only
      aerobic training decreased body weight and diastolic blood pressure. In
      conclusion, high-intensity aerobic interval training was better than moderate
      intensity aerobic training in improving aerobic work capacity and endothelial
      function. An important contribution towards improved aerobic work capacity,
      endothelial function and cardiovascular health originates from strength training,
      which may serve as a substitute when whole-body aerobic exercise is contra
      indicated or difficult to perform.

PMID- 18338981
TI  - Relationship between peripheral and coronary function using laser Doppler imaging
      and transthoracic echocardiography.
AB  - Vascular dysfunction in the coronary and peripheral circulations is an early
      prognostic marker of future cardiovascular events. Measurements of coronary and
      peripheral vascular function in resistance vessels can be made, but rely on
      invasive procedures, which make them unsuitable for routine application. An
      assessment of the direct correlation between vascular responses in skin and
      coronary vessels has not been made previously. In 27 normal healthy subjects (18
      55 years of age), we examined the relationship between peripheral and coronary
      vascular function. Cutaneous perfusion was measured using the non-invasive
      technique of laser Doppler imaging during iontophoresis of acetylcholine and
      sodium nitroprusside, and cutaneous vascular conductance was calculated (laser
      Doppler perfusion/mean arterial pressure). Coronary flow reserve was measured
      using transthoracic echocardiography during intravenous adenosine infusion. Mean
      diastolic velocities were measured at baseline and peak hyperaemic conditions
      from the Doppler signal recordings. CVR (coronary velocity reserve) was defined
      as the ratio of hyperaemic to basal mean diastolic velocities. There were
      significant positive correlations between CVR and cutaneous vascular conductance
      for acetylcholine (r=0.399, P=0.039) and sodium nitroprusside (r=0.446, P=0.020).
      These results support the idea that peripheral measurements of skin blood flow
      are representative of generalized microvascular function including that of the
      coronary circulation in normal healthy subjects.

PMID- 18338982
TI  - Regulation of Ca2+/calmodulin kinase II by a small C-terminal domain phosphatase.
AB  - We present here the identification and characterization of an SCP3 (small C
      terminal domain phosphatase-3) homologue in smooth muscle and show, for the first
      time, that it dephosphorylates CaMKII [Ca(2+)/CaM (calmodulin)-dependent protein
      kinase II]. SCP3 is a PP2C (protein phosphatase 2C)-type phosphatase that is
      primarily expressed in vascular smooth muscle tissues and specifically binds to
      the association domain of the CaMKIIgamma G-2 variant. The dephosphorylation is
      site-specific, excluding the Thr(287) associated with Ca(2+)/CaM-independent
      activation of the kinase. As a result, the autonomous activity of CaMKIIgamma G-2
      is not affected by the phosphatase activity of SCP3. SCP3 co-localizes with
      CaMKIIgamma G-2 on cytoskeletal filaments, but is excluded from the nucleus in
      differentiated vascular smooth muscle cells. Upon depolarization-induced Ca(2+)
      influx, CaMKIIgamma G-2 is activated and dissociates from SCP3. Subsequently,
      CaMKIIgamma G-2 is targeted to cortical adhesion plaques. We show here that SCP3
      regulates phosphorylation sites in the catalytic domain, but not those involved
      in regulation of kinase activation. This selective dephosphorylation by SCP3
      creates a constitutively active kinase that can then be differentially regulated
      by other phosphorylation-dependent regulatory mechanisms.

PMID- 18338983
TI  - Increased plasma urotensin-II levels are associated with diabetic retinopathy and
      carotid atherosclerosis in Type 2 diabetes.
AB  - Human U-II (urotensin-II), the most potent vasoconstrictor peptide identified to
      date, is associated with cardiovascular disease. A single nucleotide polymorphism
      (S89N) in the gene encoding U-II (UTS2) is associated with the onset of Type 2
      diabetes and insulin resistance in the Japanese population. In the present study,
      we have demonstrated a relationship between plasma U-II levels and the
      progression of diabetic retinopathy and vascular complications in patients with
      Type 2 diabetes. Eye fundus, IMT (intima-media thickness) and plaque score in the
      carotid artery, BP (blood pressure), FPG (fasting plasma glucose), HbA(1c)
      (glycated haemoglobin), U-II, angiogenesis-stimulating factors, such as VEGF
      (vascular endothelial growth factor) and heregulin-beta(1), and lipid profiles
      were determined in 64 patients with Type 2 diabetes and 24 non-diabetic controls.
      FPG, HbA(1c) and VEGF levels were significantly higher in patients with Type 2
      diabetes than in non-diabetic controls. Diabetes duration, insufficient glycaemic
      and BP control, plasma U-II levels, IMT, plaque score and nephropathy grade
      increased significantly across the subjects as follows: non-diabetic controls,
      patients with Type 2 diabetes without retinopathy (group N), patients with Type 2
      diabetes with simple (background) retinopathy (group A) and patients with Type 2
      diabetes with pre-proliferative and proliferative retinopathy (group B). The
      prevalence of obesity and smoking, age, low-density lipoprotein, triacylglycerols
      (triglycerides) and heregulin-beta(1) were not significantly different among the
      four groups. In all subjects, U-II levels were significantly positively
      correlated with IMT, FPG, and systolic and diastolic BP. Multiple logistic
      regression analysis revealed that, of the above parameters, U-II levels alone had
      a significantly independent association with diabetic retinopathy. In conclusion,
      the results of the present study provide the first evidence that increased plasma
      U-II levels may be associated with the progression of diabetic retinopathy and
      carotid atherosclerosis in patients with Type 2 diabetes.

PMID- 18338984
TI  - Vascular endothelial cell antigen (VECA), a novel secreted protein:
      overexpression in Escherichia coli of the hexahistidine- tagged protein and
      production of polyclonal antibodies.
AB  - A novel VECA (vascular endothelial cell antigen) was previously identified by
      using an antibody pool against antigens in HUVECs (human umbilical-vein
      endothelial cells). VECA has been evolutionarily conserved in vertebrate species
      ranging from frog and fish to mouse and human. Bioinformatics analysis indicated
      that VECA was 10.1 kDa in size, with a predicted signal sequence and
      transmembrane domain, indicating that VECA may have important biological
      functions. The present paper describes a procedure for obtaining and purifying
      human recombinant VECA expressed in Escherichia coli as a fusion protein, via a
      human VECA cDNA linked pQE30 expression vector to DNA coding for hexahistidine.
      The purified protein was used to raise anti-(human VECA) polyclonal antibodies,
      which were suitable for detecting the presence of VECA in cells, cell-culture
      supernatant and tissues by immunoblotting and immunohistochemistry. To our
      knowledge, this is the first study on the protein expression and polyclonal
      antibody production for human VECA. In addition, we report for the first time the
      positive identification of VECA in humans at the protein and subcellular level
      and provide the first experimental verification that VECA was indeed a secreted
      protein. The anti-(human VECA) polyclonal antibodies prepared may serve as a
      useful tool for future biological function studies on VECA.

PMID- 18338985
TI  - Covering up the crystal ball.

PMID- 18338986
TI  - Medical humanities: state of the heart.

PMID- 18338987
TI  - Checklists for assessment and certification of clinical procedural skills omit
      essential competencies: a systematic review.
AB  - OBJECTIVE: To develop generic criteria for the global assessment of clinical
      procedural competence and to quantify the extent to which existing checklists
      allow for holistic assessment of procedural competencies. METHODS: We carried out
      a systematic review and qualitative analysis of published clinical procedural
      skills assessment checklists and enumerated the contents of each. Source
      materials included all English-language papers published from 1990 to June 2005,
      identified from 18 databases, which described or referred to an assessment
      document for any clinical procedural skill. A pair of reviewers identified key
      generic themes and sub-themes through in-depth analysis of a subset of 20
      checklists with iterative agreement and independent retesting of a coding
      framework. The resulting framework was independently applied to all checklists by
      pairs of reviewers checking for the emergence of new themes and sub-themes. Main
      outcome measures were identification of generic clinical procedural skills and
      the frequency of occurrence of each in the identified checklists. RESULTS: We
      identified 7 themes ('Procedural competence', represented in 85 [97%] checklists;
      'Preparation', 65 [74%]; 'Safety', 45 [51%]; 'Communication and working with the
      patient', 32 [36%]; 'Infection control', 28 [32%]; 'Post-procedural care', 24
      [27%]; 'Team working', 13 [15%]) and 37 sub-themes, which encapsulated all
      identified checklists. Of the sub-themes, 2 were identified after the initial
      coding framework had been finalised. CONCLUSIONS: It is possible to develop
      generic criteria for the global assessment of clinical procedural skills. A third
      and a half of checklists, respectively, do not enable explicit assessment of the
      key competencies 'Infection control' and 'Safety'. Their assessment may be
      inconsistent in assessments which use such checklists.

PMID- 18338988
TI  - Can a district hospital assess its doctors for re-licensure?
AB  - CONTEXT: The Chief Medical Officer's recommendations on medical regulation in the
      UK suggest that National Health Service (NHS) trusts should assess their doctors
      and confirm whether they remain fit to practise medicine. OBJECTIVE: We set out
      to evaluate the utility of hospital trust-based assessment in a 'best-case
      scenario' within existing resources. METHODS: We carried out a generalisability
      analysis, and feasibility and validity evaluation, based on an assessment process
      for 137 career-grade doctors at Chesterfield Royal Hospital, Chesterfield, UK,
      using validated multi-source feedback (MSF) and patient rating (PR) instruments.
      RESULTS: Uptake and response rates were good for MSF (91% and 85%, respectively).
      However, only 6% of non-clinical doctors and anaesthetists, and 48% of clinical
      doctors, obtained sufficient PR ratings. Aggregate scores were acceptably
      reliable. Nine combined MSF ratings and 15 PR ratings produce standard errors of
      measurement of 0.19 on a 6-point scale and 0.15 on a 5-point scale, respectively.
      Overall aggregate scores did not identify any doctor as unsatisfactory, but 6
      doctors were scored as unsatisfactory by 2 or more colleagues or patients. These
      performance concerns appear to merit further investigation. Patients rated female
      doctors better than male doctors (4.61 versus 4.46; P < 0.05). Colleagues rated
      UK graduates better than non-UK graduates (5.31 versus 5.15; P < 0.05).
      CONCLUSIONS: This study shows that the commissioning of professional services
      makes the implementation of an assessment process linked to appraisal feasible.
      However, trust-based assessment requires significant development: developmental
      appraisal needs protection; new instruments are needed for non-clinical
      specialties; PR requires specific administrative support, and guidance is
      required over concern thresholds and demographic effects. Disaggregated
      assessment data may help identify doctors with potential performance problems.

PMID- 18338989
TI  - Implementing workplace-based assessment across the medical specialties in the
      United Kingdom.
AB  - OBJECTIVES: To evaluate the reliability and feasibility of assessing the
      performance of medical specialist registrars (SpRs) using three methods: the mini
      clinical evaluation exercise (mini-CEX), directly observed procedural skills
      (DOPS) and multi-source feedback (MSF) to help inform annual decisions about the
      outcome of SpR training. METHODS: We conducted a feasibility study and
      generalisability analysis based on the application of these assessment methods
      and the resulting data. A total of 230 SpRs (from 17 specialties) in 58 UK
      hospitals took part from 2003 to 2004. Main outcome measures included: time taken
      for each assessment, and variance component analysis of mean scores and
      derivation of 95% confidence intervals for individual doctors' scores based on
      the standard error of measurement. Responses to direct questions on
      questionnaires were analysed, as were the themes emerging from open-comment
      responses. RESULTS: The methods can provide reliable scores with appropriate
      sampling. In our sample, all trainees who completed the number of assessments
      recommended by the Royal Colleges of Physicians had scores that were 95% certain
      to be better than unsatisfactory. The mean time taken to complete the mini-CEX
      (including feedback) was 25 minutes. The DOPS required the duration of the
      procedure being assessed plus an additional third of this time for feedback. The
      mean time required for each rater to complete his or her MSF form was 6 minutes.
      CONCLUSIONS: This is the first attempt to evaluate the use of comprehensive
      workplace assessment across the medical specialties in the UK. The methods are
      feasible to conduct and can make reliable distinctions between doctors'
      performances. With adaptation, they may be appropriate for assessing the
      workplace performance of other grades and specialties of doctor. This may be
      helpful in informing foundation assessment.

PMID- 18338990
TI  - Interdisciplinary team interactions: a qualitative study of perceptions of team
      function in simulated anaesthesia crises.
AB  - OBJECTIVES: We placed anaesthesia teams into a stressful environment in order to
      explore interactions between members of different professional groups and to
      investigate their perspectives on the impact of these interactions on team
      performance. METHODS: Ten anaesthetists, 5 nurses and 5 trained anaesthetic
      assistants each participated in 2 full-immersion simulations of critical events
      using a high-fidelity computerised patient simulator. Their perceptions of team
      interactions were explored through questionnaires and semi-structured interviews.
      Written questionnaire data and interview transcriptions were entered into N6
      qualitative software. Data were analysed by 2 investigators for emerging themes
      and coded to produce reports on each theme. RESULTS: We found evidence of limited
      understanding of the roles and capabilities of team members across professional
      boundaries, different perceptions of appropriate roles and responsibilities for
      different members of the team, limited sharing of information between team
      members and limited team input into decision making. There was a perceived impact
      on task distribution and the optimal utilisation of resources within the team.
      CONCLUSIONS: Effective management of medical emergencies depends on optimal team
      function. We have identified important factors affecting interactions between
      different health professionals in the anaesthesia team, and their perceived
      influences on team function. This provides evidence on which to build appropriate
      and specific strategies for interdisciplinary team training in operating theatre
      staff.

PMID- 18338991
TI  - The search-inference framework: a proposed strategy for novice clinical problem
      solving.
AB  - CONTEXT: Medical education in the clinical clerkship years emphasises the
      systematic collection and organisation of patient information to be combined with
      domain-specific knowledge of disease processes. Eventually, novice clinical
      problem solvers will learn to recognise patterns within the patient data
      ('illness scripts') which suggest the main diagnostic possibilities. Before
      novice problem solvers develop these illness scripts, pattern recognition may not
      be effective for solving clinical problems. METHODS: This discussion paper
      describes the application of a decision framework adapted from cognitive
      psychology (the search-inference framework) to basic medical problem solving.
      Emphasis is placed on problem solving by novices who have not yet developed a
      full compliment of illness scripts. CONCLUSIONS: The search-inference framework
      is similar to the approach taken by laypersons to diagnose their own symptoms or
      solve other problems. It may be especially useful for students who have not yet
      developed a sizeable repertoire of illness scripts, and the principles described
      may also be invoked by experienced clinicians confronting difficult clinical
      problems.

PMID- 18338992
TI  - Factors affecting the utility of the multiple mini-interview in selecting
      candidates for graduate-entry medical school.
AB  - CONTEXT: We wished to determine which factors are important in ensuring
      interviewers are able to make reliable and valid decisions about the non
      cognitive characteristics of candidates when selecting candidates for entry into
      a graduate-entry medical programme using the multiple mini-interview (MMI).
      METHODS: Data came from a high-stakes admissions procedure. Content validity was
      assured by using a framework based on international criteria for sampling the
      behaviours expected of entry-level students. A variance components analysis was
      used to estimate the reliability and sources of measurement error. Further
      modelling was used to estimate the optimal configurations for future MMI
      iterations. RESULTS: This study refers to 485 candidates, 155 interviewers and 21
      questions taken from a pre- prepared bank. For a single MMI question and 1
      assessor, 22% of the variance between scores reflected candidate-to-candidate
      variation. The reliability for an 8-question MMI was 0.7; to achieve 0.8 would
      require 14 questions. Typical inter-question correlations ranged from 0.08 to
      0.38. A disattenuated correlation with the Graduate Australian Medical School
      Admissions Test (GAMSAT) subsection 'Reasoning in Humanities and Social Sciences'
      was 0.26. CONCLUSIONS: The MMI is a moderately reliable method of assessment. The
      largest source of error relates to aspects of interviewer subjectivity,
      suggesting interviewer training would be beneficial. Candidate performance on 1
      question does not correlate strongly with performance on another question,
      demonstrating the importance of context specificity. The MMI needs to be
      sufficiently long for precise comparison for ranking purposes. We supported the
      validity of the MMI by showing a small positive correlation with GAMSAT section
      scores.

PMID- 18338993
TI  - Cross-cultural adaptation of the Swedish version of Readiness for
      Interprofessional Learning Scale (RIPLS).
AB  - CONTEXT: Interprofessional learning activities in health care are being gradually
      introduced on an international basis and therefore cross-cultural and
      internationally collaborative research into the outcomes of these activities is
      needed. Hence, it is necessary not only to translate research instruments into
      the language of the culture in which they are to be used, but also to adapt them
      culturally if they are to fulfil the testing purposes for which they are
      intended. It is also necessary to test a translated instrument in order to ensure
      that it retains its intended psychometric properties. METHODS: In the present
      study, the Readiness for Interprofessional Learning Scale (RIPLS) was adapted for
      use in a Swedish student population. Cross-cultural adaptation was performed
      according to recommended guidelines. The Swedish version was tested on a group of
      students from various health care professions (n = 214). Cronbach's alpha
      coefficient was adopted to ensure internal consistency. RESULTS: Minor
      discrepancies during the different translation processes were identified and
      corrected. Confirmatory factor analysis suggests that the model had an acceptable
      fit, implying that the factor structure of the scale did not undergo any
      significant changes by being subjected to translation. The psychometric qualities
      of the instrument were comparable with those of the English-language version.
      CONCLUSIONS: This study presents the cross-cultural adaptation of the RIPLS and
      demonstrates that its subscale Teamwork and Collaboration is the only reliable
      subscale. The other 2 subscales (Professional Identity, and Roles and
      Responsibilities) probably require further scrutiny and development, at least in
      the Swedish population.

PMID- 18338994
TI  - Working in health access programme (WHAP): initial results.
AB  - CONTEXT: Academic achievement and social class are positively related and
      applications to medical schools reflect a class-based bias favouring middle-class
      candidates. Applying a measure that is class-free could be useful as an indicator
      of a potential good health professional may widen the pool of applicants. In the
      Working in Health Access Programme (WHAP), we report on the potential usefulness
      of such a measure. In addition, we describe a programme for raising awareness of
      higher education (HE) and careers in health care. METHODS: Pupils attending
      schools with low HE participation rates sat a battery of psychometric tests
      assessing both cognitive and non-cognitive skills. A total of 2349 pupils sat the
      tests and 1000 of them took part in the subsequent activities. These pupils are
      being followed up and have obtained their Standard Grade (Year 11) examination
      results. RESULTS: Although social class influenced cognitive skills, it had no
      influence on non-cognitive abilities. Pupils with high levels of cognitive
      ability were found in all classes, including the most deprived. Both the testing
      and the awareness-raising programme were successful. Additional information was
      obtained on factors influencing the participants' choices of career. CONCLUSIONS:
      Psychometric assessment could act as an early indicator for identifying potential
      in young people. For pupils with both cognitive and non-cognitive attributes that
      might indicate they would be successful in veterinary or human medicine,
      appropriate advice regarding subject choices for school examinations and future
      careers could be provided.

PMID- 18338995
TI  - The effect of gender on medical students' aspirations: a qualitative study.
AB  - OBJECTIVE: This study aimed to explore the effect of gender on medical students'
      aspirations. METHODS: The study design included purposive sampling and interim
      data interpretation to guide recruitment of medical students with a wide spectrum
      of opinions. Data were collected through audio-recorded, semi-structured, in
      depth exploratory interviews, which were transcribed verbatim. Qualitative
      analysis was carried out by a female medical student researcher. Her evolving
      interpretation was constantly compared against the original data by male (doctor)
      and female (pharmacist) staff researchers in a systematic search for internal
      corroboration or disconfirmation. Causal associations consistently present in the
      data are reported. RESULTS: Six male and six female medical students in Years 3
      and 4 shared a wish to achieve a work-life balance that allowed them to devote
      time to bringing up children while contributing usefully to society as doctors.
      However, women were readier to compromise professional attainment within their
      personal work-life balances. Their readiness derived from gendered stereotypes of
      women's social and professional roles, a lack of female professional role models,
      womens' greater awareness of the tensions between career and family, various
      other informal social influences, and a lack of positive career advice to
      counterbalance these influences. CONCLUSIONS: Better career advice and more
      flexible work opportunities are needed if the two-thirds of medical students who
      are women are to contribute specialist as well as generalist expertise to the
      medical workforce.

PMID- 18338996
TI  - Safe medication practice: attitudes of medical students about to begin their
      intern year.
AB  - OBJECTIVES: Interns are expected to prescribe effectively and safely. This study
      aimed to assess medical students' perceptions of their readiness to prescribe,
      associated risks and outcome if involved in an error, as well as their
      perceptions of available support. METHODS: We carried out a survey of 101
      students prior to their intern year using a structured questionnaire. An
      indication of agreement with 21 closed statements was sought. Thematic clusters
      were identified by factor analysis. RESULTS: Most students (84) felt they would
      be able to prescribe for most simple complaints and complete discharge
      prescriptions (81). In high-risk situations, fewer students felt comfortable with
      prescribing: only 54 felt sufficiently confident to prescribe warfarin and 66
      felt confident enough to order i.v. fluids. Many felt support such as guidelines
      was available (87) and that, if in doubt, they could clarify instructions and
      seek advice. Students were aware of errors occurring within the medication
      system; however, most (99) believed that the medicines they prescribed would be
      safely administered. There was a mixed perception of medication errors: 40 felt
      that their prescribing errors would not be dealt with constructively and 79
      indicated that a culture existed at their hospitals where clinicians would be
      blamed if they made a prescribing error. CONCLUSIONS: At the end of medical
      school education and prior to assuming responsibility for prescribing, students
      felt unprepared and perceived that negative outcomes would result if they were
      involved in errors. These findings indicate that much more work is needed to
      prepare doctors to prescribe safely, improve the safety of prescribing systems
      and address the issue of blame.

PMID- 18338997
TI  - Teaching transfusion in UK medical schools: a survey by the National Blood
      Transfusion Committee.

PMID- 18338998
TI  - Interventions for advanced communication skills.

PMID- 18338999
TI  - Learning pelvic examination with clinical teaching associates.

PMID- 18339000
TI  - Undergraduate medical education in Greece: a hostile environment for primary
      health care.

PMID- 18339001
TI  - Secretory type II phospholipase A2 in culprit coronary lesions is associated with
      myocardial infarction.
AB  - BACKGROUND: Secretory type-II phospholipase A(2) (sPLA(2)-II) is a cardiovascular
      risk marker since higher levels of this acute phase protein imply an increased
      risk for coronary artery disease. Moreover, it is hypothesized that local
      activity of sPLA(2)-II in the atherosclerotic plaque facilitates an inflammatory
      response to induce plaque instability or rupture. We have studied the presence of
      sPLA(2)-II in culprit lesions in the coronary arteries of patients with acute
      myocardial infarction (AMI) or angina pectoris. MATERIALS AND METHODS: We
      performed a histological examination of culprit lesions in 41 patients with
      stable (SAP) or unstable angina pectoris (UAP), or AMI using directed coronary
      atherectomy (DCA). Frozen slides were analysed immuno-histochemically for the
      presence of sPLA(2)-II, macrophages and smooth muscle cells. Immunopositive areas
      were calculated as a percentage of the total tissue area using image analysis
      software. RESULTS: Intracellular sPLA(2)-II was found in atherosclerotic lesions
      in the macrophages of the intima as well as in vascular smooth muscle cells. Next
      to this, extracellular sPLA(2)-II depositions were also found. These depositions
      were significantly more extensive in patients with AMI, i.e.
      26%(median)[6%(25th(percentile))-44%(75th(percentile))] of the intima area, than
      in patients with SAP 0%(median) (0%(25th)-10%(75th); P = 0.013) or UAP 0%(median)
      (0%(25th)-0%(75th); P = 0.04). CONCLUSIONS: Extracellular sPLA(2)-II is more
      abundantly present in atherosclerotic culprit lesions that have led to myocardial
      infarction. This suggests a role for extracellular sPLA(2)-II in the development
      of complications of atherosclerotic lesions in coronary arteries.

PMID- 18339002
TI  - Metabolic and anti-inflammatory benefits of eccentric endurance exercise - a
      pilot study.
AB  - BACKGROUND: Eccentric endurance exercise (e.g. hiking downwards) is less
      strenuous than concentric exercise (e.g. hiking upwards) but its potential to
      reduce cardiovascular risk is unknown. MATERIALS AND METHODS: We randomly
      allocated 45 healthy sedentary individuals (16 men and 29 women, mean age 48
      years) to one of two groups, one beginning with two months of hiking upwards, the
      other with two months of hiking downwards the same route, with a crossover for a
      further two months. For the opposite way, a cable car was used where compliance
      was recorded electronically. The difference in altitude was 540 metres; the
      distance was covered three to five times a week. Fasting and postprandial
      metabolic profiles were obtained at baseline and after the two month periods of
      eccentric and concentric exercise, respectively. RESULTS: Forty-two of the 45
      participants completed the study; the compliance rate was therefore 93%. Compared
      with baseline, eccentric exercise lowered total cholesterol (by 4.1%; P = 0.026),
      low-density lipoprotein (LDL) cholesterol (by 8.4%, P = 0.001), Apolipoprotein
      B/Apolipoprotein A1 ratio (by 10.9%, P < 0.001), homeostasis model assessment of
      insulin resistance scores (by 26.2%, P = 0.017) and C-reactive protein (by 30.0%;
      P = 0.007); the magnitude of these changes was comparable to that of concentric
      exercise. Eccentric exercise improved glucose tolerance (by 6.2%, P = 0.023),
      whereas concentric exercise improved triglyceride tolerance (by 14.9%, P =
      0.022). CONCLUSIONS: Eccentric endurance exercise is a promising new exercise
      modality with favourable metabolic and anti-inflammatory effects and is well
      applicable to sedentary individuals.

PMID- 18339003
TI  - Glucose turnover and intima media thickness of internal carotid artery in type 2
      diabetes offspring.
AB  - BACKGROUND: First-degree offspring (OFF) of type 2 diabetic (T2DM) patients bear
      a approximately 40% lifetime risk of developing T2DM. They are insulin resistant
      and carry a risk of premature atherosclerosis, the extent of which can be
      estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this
      study examines parameters of glucose and lipid metabolism, insulin sensitivity,
      beta cell function (BCF) and IMT with their interrelationships in middle-aged
      OFF. MATERIALS AND METHODS: T2DM-OFF (n = 18, 14f/4m, 45.6 +/- 2.1 years, BMI: 26
      +/- 1 kg m(-2)) were compared with 18 matching humans without a family history of
      diabetes (CON; 14f/4m, 44.5 +/- 2.1 years, BMI: 24 +/- 1 kg m(-2); each P >
      0.30), all with normal glucose tolerance as tested by three-hour (75 g) oral
      glucose tolerance tests (OGTT). Two-hour hyperinsulinaemic (40 mU min(-1).m(
      2))isoglycaemic clamp tests were performed with simultaneous measurement of
      endogenous glucose (D-[6,6-(2)H(2)]glucose) production (EGP). IMT [internal
      (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by
      Adaptation Index (AI). RESULTS: Before and during OGTT, both groups were similar
      in plasma glucose, insulin, C-peptide and free fatty acids (FFA), whereas OFF
      showed ~30% lower (P < 0.03) fasting plasma triglycerides before OGTT. During
      hyperinsulinaemic clamps, insulin sensitivity was approximately 38% lower (P <
      0.03) in OFF who showed higher plasma FFA (44 +/- 9 micromol L(-1)) than CON (26
      +/- 3 micromol L(-1), P < 0.05) after 90 min. EGP was similar in both groups. OFF
      had 38% (P < 0.007) reduced AI. ICA-IMT was approximately 18% higher in OFF (P <
      0.002), but did not correlate with insulin sensitivity. CONCLUSION: The data
      obtained show middle-aged T2DM-OFF with normal glucose tolerance displaying
      reduced total insulin sensitivity and impaired beta cell function, which relates
      to impaired insulin-dependent suppression of plasma FFA and increased ICA-IMT.

PMID- 18339004
TI  - Alterations of hepatic ATP homeostasis and respiratory chain during development
      of non-alcoholic steatohepatitis in a rodent model.
AB  - BACKGROUND: Mitochondrial dysfunction is considered a key player in non-alcoholic
      steatohepatitis (NASH) but no data are available on the mitochondrial function
      and ATP homeostasis in the liver during NASH progression. In the present paper we
      evaluated the hepatic mitochondrial respiratory chain activity and ATP synthesis
      in a rodent model of NASH development. MATERIALS AND METHODS: Male Wistar rats
      fed a High Fat/Methionine-Choline Deficient (MCD) diet to induce NASH or a
      control diet (SHAM), and sacrificed after 3, 7 and 11 weeks. The oxidative
      phosphorylation, the F(0)F(1)ATPase (ATP synthase) and the ATP content were
      assessed in liver mitochondria. RESULTS: NASH mitochondria exhibited an increased
      rate of substrate oxidation at 3 weeks, which returned to below the normal level
      at 7 and 11 weeks, concomitantly with the coupling between the phosphorylation
      activity and the mitochondrial respiration (ADP/O). Uncoupling of NASH liver
      mitochondria did not allow the recovery of the maximal respiration rate at 7 and
      11 weeks. The ATPase (ATP synthase) activity was similar in NASH and SHAM rats,
      but the mitochondrial ATP content was significantly lower in NASH livers.
      CONCLUSIONS: The loss of hepatic ATP stores is not dependent on the F(0)F(1)
      ATPase but resides in the respiratory chain. Dysfunction of both Complex I and II
      of the mitochondrial respiratory chain during NASH development implies a
      mitochondrial adaptive mechanism occurring in the early stages of NASH.

PMID- 18339005
TI  - Classification of chronic kidney disease by estimated glomerular filtration rate.
AB  - BACKGROUND: Serum creatinine concentration alone as a marker of kidney function
      is inadequate. Thus several equations for estimating glomerular filtration rate
      (eGFR) have been proposed within the last years. PATIENTS AND METHODS: In our
      study we compared three frequently used equations, the abbreviated modification
      of diet in renal disease (MDRD) formula, the extended MDRD formula and the
      recently proposed Mayo clinic equation in a large patient cohort. RESULTS: A
      total of 244 507 patients attending the Vienna General Hospital were evaluated
      for their kidney function and three equations for eGFR were compared. The median
      age of the patients was 51 years (ranging from 18.0 to 102.6 years) with 44.3%
      males (n = 108 527). We observed a significant increase of patients with eGFR
      classes four and five (according to Kidney Disease Outcomes Quality Initiative
      (K/DOQI) guidelines) with advanced age. Whereas approximately 1% of patients < 30
      years presented with eGFR classes four and five (defined as eGFR < 30 mL min(-1)
      1.73 m(-2)), this prevalence increased up to approximately 12% in patients at the
      age of 80 years or older. All three equations showed comparable results for eGFR
      classes four and five. The proportion of patients with mild to moderate
      impairment of kidney function is higher using both MDRD equations. CONCLUSIONS:
      The MDRD equations (particularly the abbreviated MDRD formula) result in
      considerably higher rates of eGFR classes two and three compared to the Mayo
      Clinic equation, while all three were comparable in classes four and five. This
      should be considered when eGFR is used in the diagnosis of chronic kidney
      disease.

PMID- 18339006
TI  - Different allergenic activity of grass pollen allergens revealed by skin testing.
AB  - BACKGROUND: Grass pollen is one of the most important allergen sources. The aim
      of this study was to compare the in vivo allergenic activity of two recently
      characterized major grass pollen allergens, Phl p 4 and Phl p 13, with three
      established major grass pollen allergens, Phl p 1, Phl p 2 and Phl p 5 as a basis
      for the formulation of a grass pollen allergy vaccine based on purified
      allergens. MATERIAL AND METHODS: Eighty-two grass pollen allergic patients were
      skin prick tested with serial dilutions of approximately equimolar concentrations
      of the purified allergens in a double-blind study. RESULTS: Phl p 4 and Phl p 13
      were identified as major grass pollen allergens according to IgE binding
      frequency (Phl p 4: 85%; Phl p 13: 56%), but exhibited a five to nine-fold lower
      allergenic skin reactivity compared to Phl p 1, Phl p 2 or Phl p 5. CONCLUSION:
      Our results indicate that Phl p 4 and Phl p 13 are not essential components for a
      therapeutic grass pollen vaccine and underpin the importance of evaluating the in
      vivo allergenic activity of individual allergens for the formulation of
      therapeutic vaccines based on purified allergens.

PMID- 18339007
TI  - Magnetic resonance guided focused ultrasound surgery. Ablation of soft tissue at
      bone-muscle interface in a porcine model.
AB  - BACKGROUND: Pain management treatments of patients with bone metastases have
      either efficacy problems or significant side effects. Percutaneous radiofrequency
      ablation has recently proved to be of palliative value. Magnetic resonance guided
      focused ultrasound surgery (MRgFUS) uses focused ultrasonic energy to non
      invasively create a heat-coagulated lesion deep within the body in a controlled,
      accurate manner. The surgeon can monitor and control energy deposition in real
      time. This technology represents a potential treatment modality in oncological
      surgery. We investigated the ability of two MRgFUS methods to accurately and
      safely target and ablate soft tissue at its interface with bone. MATERIALS AND
      METHODS: Heat-ablated lesions were created by MRgFUS at the bone-muscle interface
      of 15 pigs. Two different methods of energy delivery were used. Temperature rise
      at the target adjacent to bone was monitored by real time MR thermal images.
      Results were evaluated by MRI (magnetic resonance imaging), nuclear scanning and
      by histopathological evaluation. RESULTS: Soft tissue lesion sizes by both
      methods were in the range of 1-2 cm in diameter. Targeting the focus 'behind' the
      bone, achieved the same result with a single sonication only. Follow up MRI and
      histopathological examination of all lesions showed focal damage at its interface
      with bone and localized damage to the outer cortex on the side closer to the
      targeted tissue. There was no damage to non-targeted tissue. CONCLUSION: MRgFUS
      by both energy deposition methods can be used to produce controlled well
      localized damage to soft tissue in close proximity to bone, with minimal
      collateral damage.

PMID- 18339008
TI  - Severe aseptic inflammation caused by long distance running (246 km) does not
      increase procalcitonin.
AB  - BACKGROUND: The Spartathlon ultra distance running race (246 kilometres) is an
      exhausting physical exercise leading to a state of systemic inflammation
      associated with dramatic elevation of interleukin-6 and acute-phase reactants to
      levels seen only in critically ill or patients near death. We sought to study the
      effect of this severe inflammatory response on the levels of serum procalcitonin.
      MATERIALS AND METHODS: Fifteen healthy endurance-trained runners who participated
      in the 2006 Spartathlon were studied. Blood samples were taken the day before the
      race, within 15 min after the end of the race and 48 h after the end of the race.
      Serum interleukin-6, serum amyloid A protein, C-reactive protein, tumour necrosis
      factor-alpha and procalcitonin concentrations were determined. RESULTS: Serum
      interleukin-6, serum amyloid A protein and C-reactive protein were dramatically
      increased after the end of the race (150-, 116- and 10,470- fold increase of the
      mean values, respectively). Procalcitonin levels remained within normal range
      (mean +/- standard error of mean, 0.27 +/- 0.02 microg L(-1), 0.26 +/- 0.02
      microg L(-1) and 0.27 +/- 0.02 microg L(-1) before, at the end, and 48 h after
      the race, respectively). Tumour necrosis factor-alpha measurements revealed no
      significant changes. CONCLUSIONS: This study provides strong evidence that
      Spartathlon, a prolonged endurance exercise resulting in severe stimulation of
      inflammatory mediators followed by muscle and liver damage, does not induce
      procalcitonin secretion. The findings cannot directly be applied to other causes
      of aseptic inflammation.

PMID- 18339010
TI  - FOXN1 homozygous mutation associated with anencephaly and severe neural tube
      defect in human athymic Nude/SCID fetus.
AB  - The forkhead, Fox, gene family comprises a diverse group of 'winged-helix'
      transcription factors that play important roles in development, metabolism,
      cancer and aging. Recently, several forkhead genes have been demonstrated to play
      critical roles in lymphocyte development and effector functions. Alterations of
      the FOXN1 gene in both mice and humans result in a severe combined
      immunodeficiency caused by an intrinsic defect of the thymus associated with
      congenital alopecia (Nude/severe combined immunodeficiency phenotype). FOXN1 is a
      member of the class of proteins involved in the development and differentiation
      of the central nervous system. We identified a human fetus homozygous for a
      mutation in FOXN1 gene who lacked the thymus and also had abnormal skin,
      anencephaly and spina bifida. Moreover, we found that FOXN1 gene is expressed in
      mouse developing choroid plexus. These observations suggest that FOXN1 may be
      involved in neurulation in humans.

PMID- 18339012
TI  - Abstracts of the Thoracic Society of Australia and New Zealand and the Australian
      and New Zealand Society of Respiratory Science Annual Scientific Meetings. March
      28-April 2, 2008. Melbourne, Australia.

PMID- 18339013
TI  - Important findings in respiratory medicine.

PMID- 18339014
TI  - Respirology year-in-review 2007: Clinical science.

PMID- 18339015
TI  - Pulmonary complications of HIV infection.
AB  - The AIDS epidemic has had a devastating global impact in the last two decades;
      although prevalence rates are low in Asia and the Pacific, their enormous
      population is associated with an estimated 1 million people infected with HIV in
      2006 alone. Survival from what had been a uniformly fatal illness has improved
      markedly with combination antiretroviral therapy and restoration of the immune
      system, but these treatments are expensive and difficult to distribute to the
      millions who need them around the world. In addition, millions more do not know
      they are infected with HIV until they develop an opportunistic infection. The
      lungs are the most frequent sites of these infections, and in different
      geographic regions, tuberculosis, bacterial pneumonia and Pneumocystis jiroveci
      are the dominant pathogens. The incidences of lung cancer and HIV-associated
      pulmonary arterial hypertension are also increasing in patients with HIV
      infection, and with the use of antiretrovirals, inflammatory disorders associated
      with immune restoration are being recognized.

PMID- 18339016
TI  - Involvement of the p38 MAPK pathway in IL-13-induced mucous cell metaplasia in
      mouse tracheal epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: IL-13 has been shown to play a pivotal role in mucous
      cell metaplasia, which is an important feature of the pathogenesis of asthma.
      However, the signalling pathways evoked by IL-13 in airway epithelial cells
      remain unclear. This study investigated the signalling mechanism of IL-13-induced
      mucous cell metaplasia in primary cultures of mouse tracheal epithelial cells
      (mTEC). METHODS: mTEC were cultured in an air-liquid interface system in the
      presence or absence of IL-13. Goblet cell hyperplasia was evaluated
      quantitatively by immunofluorescent staining for MUC5AC, which is a major
      component of airway mucins. Western blotting was used to assess activation of the
      signalling molecules, signal transducer and activator of transcription 6 (STAT6),
      p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated
      kinase (ERK) 1/2. MUC5AC gene expression was measured by RT-PCR. RESULTS: IL-13
      induced mucous cell metaplasia for 7-14 days in mTEC. IL-13 phosphorylated STAT6
      within 20 min, whereas it induced delayed phosphorylation of p38 MAPK 36-48 h
      after stimulation. In contrast, ERK1/2 was constantly activated and was not
      enhanced by IL-13. An inhibitor of p38 MAPK (SB202190) suppressed mucous cell
      differentiation in a concentration-dependent manner. In STAT6 knockout mice, IL
      13 failed to induce mucous cell metaplasia and activate p38 MAPK. Cycloheximide
      also diminished activation of p38 MAPK and induction of MUC5AC mRNA expression by
      IL-13. CONCLUSIONS: The p38 MAPK pathway is involved in IL-13-induced mucous cell
      metaplasia and MUC5AC mRNA regulation in mTEC. In addition, p38 MAPK
      phosphorylation may require STAT6-dependent de novo protein synthesis induced by
      IL-13.

PMID- 18339017
TI  - Analysis of gene expression in human bronchial epithelial cells upon influenza
      virus infection and regulation by p38 mitogen-activated protein kinase and c-Jun
      N-terminal kinase.
AB  - BACKGROUND AND OBJECTIVE: Airway epithelial cells, which are the initial site of
      influenza virus (IV) infection, participate in the inflammatory process through
      the expression of various genes. In this process, mitogen-activated protein
      kinase (MAPK) may be associated with the expression of many genes, but its
      precise role remains unknown. METHODS: A comprehensive analysis was performed of
      gene expression in human bronchial epithelial cells upon IV infection, using an
      Affymetrix gene chip containing 12 000 genes. Regulation of gene expression by
      MAPK was also analysed. RESULTS: A total of 5998 genes were detected. Upon IV
      infection, 165 genes were upregulated and 49 of these were interferon-stimulated
      genes. The functions of 129 genes, including 14 apoptosis-related genes and 6
      antiviral genes, were well characterized; however, those of 36 genes were
      unknown. The expression of 29 genes was inhibited either by SB 203580, a specific
      inhibitor of p38 MAPK, or by CEP-11004, a specific inhibitor of the c-Jun-N
      terminal kinase (JNK) cascade, and the percentage inhibition by SB 203580
      correlated with that by CEP-11004, suggesting that p38 and JNK participate in a
      common downstream pathway involved in the regulation of gene expression. p38 MAPK
      or JNK-dependent genes were functionally classified into diverse categories.
      CONCLUSIONS: Although further studies are needed to obtain a more complete
      understanding of gene expression and the role of MAPK in gene expression, the
      present results are important in understanding the molecular mechanisms involved
      in the response of bronchial epithelial cells to IV infection.

PMID- 18339018
TI  - Erythromycin attenuates MUC5AC synthesis and secretion in cultured human tracheal
      cells infected with RV14.
AB  - BACKGROUND AND OBJECTIVE: The common cold is a major cause of asthma exacerbation
      and chronic obstructive lung disease. Rhinovirus is reported to be responsible
      for more than 50% of cases of the common cold. In a previous study, we reported
      that rhinovirus infection of cultured airway cells induced MUC5AC mucin
      overproduction and hypersecretion by activating the p44/42 mitogen-activated
      protein kinase (p44/42 MAPK) pathway. The aim of this study was to examine the
      effect of erythromycin on RV14-induced airway mucin overproduction and
      hypersecretion. METHODS: RV14-infected human tracheal epithelial cells were
      treated with erythromycin. RESULTS: Erythromycin blocked RV14-induced MUC5AC
      protein overproduction and hypersecretion, and also blocked RV14-induced p44/42
      MAPK activation in the cells. CONCLUSIONS: Erythromycin may attenuate RV14
      induced MUC5AC overproduction and hypersecretion by blocking the p44/42 MAPK
      pathway or its upstream regulators.

PMID- 18339019
TI  - Pharmacokinetics of clarithromycin in bronchial epithelial lining fluid.
AB  - BACKGROUND AND OBJECTIVE: BAL is an established technique for measuring
      antibiotic concentrations in the epithelial lining fluid (ELF) of the bronchiolar
      alveolar regions. However, the results may not reflect concentrations in
      bronchial regions. Bronchoscopic microsampling (BMS) is a technique for repeated
      sampling of bronchial ELF. The objective of the present study was to determine
      the time versus concentration profile of clarithromycin and its active
      metabolite, 14-hydroxy-clarithromycin, in bronchial ELF, as determined by BMS.
      METHODS: BMS was performed at 1, 2, 3, 5 and 10 h after a single oral
      administration of 200 mg clarithromycin in five healthy volunteers. BAL was
      performed 3 h after administration to determine clarithromycin concentrations in
      alveolar ELF and alveolar macrophages (AM). RESULTS: The maximum concentration
      (C(max)) of clarithromycin was 0.36 +/- 0.07 mg/L in serum and 1.44 +/- 0.49 mg/L
      in bronchial ELF (P < 0.01). C(max) for 14-hydroxy-clarithromycin was 0.34 +/-
      0.13 mg/L in serum and 0.68 +/- 0.34 mg/L in bronchial ELF. The area under the
      concentration-time curve from 0 to 10 h (AUC(0-10)) for clarithromycin was 2.10
      +/- 0.49 mg.h/L for serum and 7.37 +/- 2.07 mg.h/L for bronchial ELF (P < 0.01).
      The concentrations of clarithromycin in alveolar ELF and AM, 3 h after oral
      administration, were 4.84 +/- 3.39 mg/L and 10.7 +/- 8.7 mg/L, respectively.
      CONCLUSIONS: A single oral dose of clarithromycin produces a significantly higher
      C(max) and AUC(0-10) for clarithromycin in bronchial ELF than in serum, and
      higher concentrations in alveolar ELF and AM than in serum. BMS might be useful
      for measuring the pharmacokinetic profile of clarithromycin in bronchial ELF.

PMID- 18339020
TI  - Rapid non-genomic effects of glucocorticoids on oxidative stress in a guinea pig
      model of asthma.
AB  - BACKGROUND AND OBJECTIVE: Glucocorticoids (GC) may exert therapeutic effects in
      asthma by a rapid non-genomic mechanism. The lungs of asthmatic patients are
      exposed to oxidative stress, which is believed to be critical in the pathogenesis
      of asthma. The aim of this study was to investigate whether GC exert a rapid non
      genomic effect on oxidative stress in asthmatic guinea pigs. METHODS: The guinea
      pig asthma model was used to assess inhibitory effects of budesonide (BUD) on
      oxidative stress. BAL fluid (BALF), trolox equivalent antioxidant capacity and
      lung manganese superoxide dismutase (MnSOD) activity were measured by
      spectrophotometry. Superoxide anion production was measured by cytochrome c
      reduction assay. RESULTS: Oxidative stress occurred within minutes following
      antigen challenge and BUD reduced the severity of oxidative stress in asthmatic
      guinea pigs within 15 min. BUD significantly decreased BALF trolox equivalent
      antioxidant capacity and lung MnSOD activity, as compared with those of vehicle
      treated asthmatic guinea pigs (P < 0.05). Additionally, BUD rapidly inhibited in
      vitro superoxide anion production by BALF cells and bronchi harvested from
      sensitized animals. These rapid effects were not blocked by the GC receptor
      antagonist RU486 and/or the protein synthesis inhibitor cycloheximide.
      CONCLUSIONS: BUD reduced oxidative stress in a guinea pig model of asthma by a
      rapid non-genomic mechanism. These data suggest new mechanisms whereby GC
      treatments may benefit asthma.

PMID- 18339021
TI  - Effects of independent lung ventilation and lateral position on cytokine markers
      of inflammation after unilateral lung acid injury in dogs.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to compare the effects of
      conventional ventilation, lateral (non-injured lung-dependent) position,
      asynchronous and synchronous independent lung ventilation on inflammatory markers
      in an animal model of unilateral lung acid injury. METHODS: Twenty-eight dogs
      underwent unilateral endobronchial instillation with hydrochloric acid and
      randomly received (n = 7 in each group) conventional ventilation in the supine
      (group I) or lateral position (group II), and independent lung ventilation in
      asynchronous (group III) or synchronous (group IV) modes. Arterial blood gases
      and serum cytokine levels were assessed at baseline, and 5 min and 4 h after
      mechanical ventilation. At the end of the study, cytokine levels were measured in
      individual lung lavage fluid. In three animals per group, differential lung
      perfusion was detected using a dual-head gamma camera. RESULTS: Unilateral acid
      injury alone worsened oxygenation as determined by the ratio of PaO(2) to
      fraction of inspired oxygen (PaO(2)/FiO(2)) and increased serum cytokine levels.
      Mean oxygenation (SD) was significantly preserved in group II, 338 (26); group
      III, 396 (28); and group IV, 395 (22) compared with group I, 173 (18) (all P <
      0.01). Serum IL-8, left-lung lavage IL-8 and matrix metalloproteinase-9 levels
      were significantly lower in groups II-IV (all P < 0.05). Only group I showed
      significantly different left and right lung lavage fluid cytokine levels. Groups
      III and IV showed slightly decreased left lung perfusion. Cytokine levels and
      oxygenation were similar in groups III and IV. CONCLUSIONS: In this model of
      unilateral lung acid injury, lateral position and independent lung ventilation
      preserved oxygenation and attenuated the inflammatory response in serum and
      injured lung BAL fluid.

PMID- 18339022
TI  - Antimicrobial susceptibilities of Streptococcus pneumoniae isolated from adult
      patients with community-acquired pneumonia in Japan.
AB  - BACKGROUND AND OBJECTIVE: Streptococcus pneumoniae (S. pneumoniae) is the most
      common pathogen associated with community-acquired pneumonia and its resistance
      to antimicrobials is a worldwide problem. The aim of this study was to
      investigate the current drug susceptibilities of S. pneumoniae isolated from
      adult patients with community-acquired pneumonia in Japan. METHODS: S. pneumoniae
      strains isolated from adult patients with pneumococcal pneumonia from 10
      institutions were collected prospectively between May 2003 and October 2004 and
      tested for drug susceptibilities. Clinical data were analysed and the risk
      factors for drug resistance investigated. RESULTS: A total of 141 isolates of S.
      pneumoniae were analysed. Of these S. pneumoniae isolates, 46.1% had intermediate
      penicillin resistance and the minimum inhibitory concentration (MIC) occurring in
      the greatest number of isolates and MIC90 value was 2 microg/mL. The prevalence
      of resistance to macrolides was 80%, with the MIC90 values being greater than or
      equal to 16 microg/mL. Approximately 40% of the strains were resistant to oral
      third-generation cephems. Penicillin and erythromycin resistance were both
      associated with the pre-existing chronic disease states. CONCLUSIONS: The cephem
      and macrolide resistance of S. pneumoniae was higher than penicillin resistance
      in adult patients with community-acquired pneumococcal pneumonia in Japan. We
      recommend that bacterial identification and sensitivities are determined in areas
      where the macrolide resistance to S. pneumoniae is high.

PMID- 18339023
TI  - Pulmonary cryptococcosis: Clinical, radiographical and serological markers of
      dissemination.
AB  - BACKGROUND AND OBJECTIVE: This study aimed to identify markers of disseminated
      infection in patients presenting with pulmonary cryptococcosis. METHODS: Patients
      diagnosed with pulmonary cryptococcosis at a tertiary hospital between April 1998
      and April 2005 were included and their clinical, radiological and pathological
      data analysed retrospectively. RESULTS: Thirty-one patients (14 male) were
      recruited into the study. Disseminated infection was seen in nine patients (29%),
      with the isolation of Cryptococcus neoformans from the blood of five patients and
      the cerebrospinal fluid of seven (three patients had both positive blood and
      cerebrospinal fluid findings). Patients with disseminated infection had a
      significantly higher incidence of impaired cellular immunity (immunosuppressant
      use, AIDS and haematological malignancy) (P = 0.015), fever (P < 0.001),
      interstitial abnormalities on CXR (P < 0.001), pleural effusion (P = 0.017) and
      death (P = 0.04) when compared with patients with localized infection. Serum
      cryptococcal antigen (sCRAG) was positive in 17 of the 19 patients tested at the
      time of diagnosis. Significantly higher sCRAG titres were noted in patients who
      had fever (P = 0.001), interstitial abnormalities on CXR (P = 0.004), pleural
      effusion (P = 0.018), disseminated disease (P = 0.003) and in those who died (P =
      0.05). CONCLUSIONS: In pulmonary cryptococcosis patients, the presence of fever,
      interstitial abnormalities on CXR or pleural effusion should lead clinicians to
      suspect disseminated infection. High titres of sCRAG may indicate more extensive
      extra-pulmonary involvement and a worse prognosis.

PMID- 18339024
TI  - Pulmonary coccidioidomycosis found in healthy Japanese individuals.
AB  - BACKGROUND AND OBJECTIVE: Coccidioidomycosis is endemic in the south-western USA.
      This study described the clinicopathological features of pulmonary
      coccidioidomycosis found in otherwise healthy Japanese individuals. METHODS: Four
      male patients with pulmonary coccidioidomycosis were assessed by clinical
      examination, serology, PCR assay, high-resolution computed tomography and
      histopathological findings. RESULTS: All patients had returned to Japan from the
      USA and all presented with an abnormal CXR during routine assessment; two of the
      patients were symptomatic. High-resolution computed tomography showed a well
      defined homogenous nodule or mass adjacent to the pleura. All patients underwent
      surgical wedge resection. Histopathological examination revealed encapsulated
      caseating epithelioid cell granulomas containing spherules and endospores. Serum
      IgG antibody was negative in all patients, but PCR assay using DNA from resected
      specimens demonstrated the presence of coccidioides-specific DNA. CONCLUSIONS:
      Pulmonary coccidioidomycosis is very rare in Japan, but it can be found
      incidentally during routine evaluation. The main high-resolution computed
      tomography findings are a well-defined homogenous nodule adjacent to the pleura,
      reflecting the histological feature of encapsulated granulomas. PCR assay is
      useful for confirming the presence of coccidioides.

PMID- 18339025
TI  - Respiratory infections and lung function in an Australian Aboriginal community.
AB  - BACKGROUND AND OBJECTIVE: To investigate the association between serological
      evidence of past infections with common respiratory pathogens and lung function
      in members of an isolated community of Aborigines from tropical coastal north
      western Australia. METHODS: FEV(1) and FVC were assessed by dry bellows
      spirometer. Serum IgG titres to 11 common respiratory pathogens were assayed.
      Smoking history was assessed by questionnaire. Reciprocal positive IgG titres
      were taken as >or=10 for all pathogens with the exception of Legionella spp.
      (>or=40) and Burkholderia pseudomallei (>or=20). Linear regression analysis
      examined associations between titres and lung function after adjustment for age,
      height, gender and smoking, separately for adults (age > 17 years) and children.
      RESULTS: An increased total number of positive IgG titres was significantly
      associated with reduced FEV(1) (P = 0.01) and FEV(1)/FVC ratio (P = 0.01)
      suggesting the presence of airflow obstruction. This association was independent
      of age, gender, height, weight and smoking status. CONCLUSIONS: The burden of
      past respiratory infections may be an important determinant of airway function in
      this Aboriginal community.

PMID- 18339026
TI  - Torque teno virus DNA titre elevated in idiopathic pulmonary fibrosis with
      primary lung cancer.
AB  - BACKGROUND AND OBJECTIVE: IPF is an independent risk factor for lung cancer, but
      the mechanism of this association has not fully been elucidated. The role of
      Torque teno virus (TTV) in respiratory disease is poorly understood, although it
      has been shown that infection with TTV is associated with the activity and
      prognosis of IPF. This study aimed to investigate the prevalence and titre of TTV
      DNA among patients with IPF and lung cancer. METHODS: The presence of TTV DNA was
      determined by PCR in the sera of patients with both lung cancer and IPF (n = 22),
      patients with IPF only (n = 35), and patients with lung cancer only (n = 142).
      RESULTS: TTV DNA was detectable in all patients with both IPF and lung cancer, in
      94.3% of the patients with IPF only and 97.2% of the patients with lung cancer
      only. The TTV DNA titre in the patients with IPF and lung cancer was
      significantly higher than that in the patients with IPF only or lung cancer only.
      The percentage of TTV-positive patients with a high TTV titre in the IPF and lung
      cancer group was significantly higher than that in the IPF only group.
      CONCLUSIONS: These findings are the first report on the association between TTV
      and the complication of lung cancer in IPF and suggest that TTV infection might
      be associated with the development of lung cancer in IPF.

PMID- 18339027
TI  - Whole-blood interferon-gamma assay for the diagnosis of tuberculosis infection in
      an unselected Greek population.
AB  - BACKGROUND AND OBJECTIVE: Although QuantiFERON-TB Gold (QFT-G) has been approved
      for the diagnosis of latent tuberculosis infection (LTBI), there are limited data
      regarding its performance in routine clinical practice. The aim of this study was
      to compare QFT-G 'In Tube' results, based on stimulation with Mycobacterium
      tuberculosis-specific antigens, with tuberculin skin test (TST) results in an
      unselected hospital-based Greek population. METHODS: This was a prospective study
      of inpatients and outpatients in the University Hospital of Larissa, Greece.
      Demographic, clinical and microbiological data were collected and correlated to
      the QFT-G 'In Tube' results. Agreement was tested using the Q-test; kappa
      coefficient and confounding factors were adjusted for by univariate and
      multivariable logistic regression. RESULTS: Among the 191 patients with valid
      results for both tests, the concordance between the TST and the QFT-G was 68.5%,
      with a kappa value of 0.38 (95% CI 0.2-0.5). In 27 (14.1%) patients with active
      tuberculosis, QFT-G 'In Tube' yielded 85.1% positive results compared with 74%
      for the TST (P = 0.45). CONCLUSIONS: Overall agreement between the QFT-G 'In
      Tube' assay and the TST in this unselected hospital population was low, mainly
      due to discordant TST-positive/QFT-negative results.

PMID- 18339028
TI  - Prognostic factors of tracheobronchial mucoepidermoid carcinoma--15 years
      experience.
AB  - BACKGROUND AND OBJECTIVES: Mucoepidermoid carcinoma of the tracheobronchial tree
      is a rare tumour which displays a variable degree of clinical aggressiveness and
      malignancy. The relationship between the patient's prognosis and the tumour's
      histological features and clinical behaviour is uncertain. The aim of this study
      was to identify the clinicopathological features and analyse the outcomes of
      patients with this type of cancer. METHODS: A retrospective analysis of the
      medical records of patients diagnosed with mucoepidermoid carcinoma of the lung
      between 1991 and 2006 was conducted. RESULTS: The study comprised 15 patients.
      Higher histological grade tumours had a higher proportion of squamoid cells (P =
      0.019); the tumours of patients with lymph node metastases also had a higher
      proportion of squamoid cells than did the tumours of patients without lymph node
      metastases (P = 0.015). Patients with early stage tumours (stage IA, IB, IIB) had
      better outcomes (10-year survival rate = 87.5%), than did patients with late
      stage tumours (stage IIIB, IV) (1-year survival rate = 28.6%; 2-year survival
      rate = 0%, P = 0.001). Patients with lower-grade tumours (grade 1 and grade 2)
      had better outcomes (1-year survival rate = 80%; 5-year survival rate = 57.1%)
      than did patients with higher-grade tumours (grade 3) (1-year survival rate =
      20%, P = 0.035). Tumour staging was a significant independent predictor of
      survival on Cox proportional hazards analysis. CONCLUSIONS: The proportion of
      squamoid cells on tumour histology may be an indicator of the level of tumour
      malignancy. Tumour, node, metastasis staging is a significant determinant of
      prognosis in patients with tracheobronchial mucoepidermoid carcinoma.

PMID- 18339029
TI  - Vascular endothelial growth factor in epithelial lining fluid of patients with
      acute respiratory distress syndrome.
AB  - BACKGROUND AND OBJECTIVE: Vascular endothelial growth factor (VEGF) is known to
      contribute to the development of pulmonary oedema, and has been suggested to have
      a protective role against lung injury. To determine the role of VEGF in acute
      lung injury (ALI) and ARDS, VEGF levels were measured in lung epithelial lining
      fluid (ELF) collected from patients with ALI/ARDS. METHODS: Forty patients with
      ALI/ARDS underwent bronchoscopic microsampling to collect ELF on days 0 (onset of
      ALI/ARDS), 1, 3, 5, 7 and 10, unless the patient was extubated or had died.
      Twelve patients, who underwent bronchoscopy for examination of small, peripheral
      pulmonary nodules, served as controls. RESULTS: The initial (day 0) levels of
      VEGF in ELF of the ALI/ARDS patients who survived and those who did not were 5.5
      ng/mL (IQR: 2.3-19.7) and 1.7 ng/mL (IQR: 0.0-6.4), respectively. On days 0, 5, 7
      and 10, the VEGF levels in ELF were significantly greater in survivors than in
      non-survivors (P < 0.05). VEGF levels on days 1 and 3 did not differ between
      survivors and non-survivors. There was no significant difference in ELF VEGF
      levels between control subjects and patients with ALI/ARDS at any time point.
      Lung injury score was inversely correlated with VEGF concentration in ELF (P <
      0.001). CONCLUSIONS: In patients with ALI/ARDS, elevated VEGF levels in ELF may
      predict a better outcome. Increased production of VEGF in the injured lung may
      contribute to resolution of inflammation in the lung.

PMID- 18339030
TI  - Submucosal gland cells in human lower airways produce MUC5AC protein.
AB  - BACKGROUND AND OBJECTIVE: It is now considered that the major component of mucus,
      MUC5AC, is mainly produced by goblet cells but not submucosal glands, and the
      role of the submucosal glands in the production of MUC5AC is unclear. The aim of
      this study was to clarify whether human submucosal glands produce MUC5AC.
      METHODS: Immunohistochemical analysis with MUC5AC antibody of lower airways
      resected from six lung cancer patients and three patients with acute myocardial
      infarction was performed. RESULTS: The submucosal glands contained both MUC5AC
      positive cells and non-positive cells. CONCLUSIONS: These data suggest that
      MUC5AC protein is produced in both goblet cells and in airway submucosal glands.

PMID- 18339031
TI  - Airway responses to salbutamol after exposure to chemical warfare.
AB  - BACKGROUND AND OBJECTIVES: Increased airway responsiveness to beta-agonists is
      noted in asthmatics and smokers. The lung may be exposed to chemical warfare
      agents such as mustard gas and pulmonary complications of exposure range from no
      effect to severe bronchial stenosis. There is little understanding of airway
      hyperresponsiveness to beta-agonist drugs in chemical war victims and this study
      examined airway responsiveness to salbutamol in victims of chemical warfare.
      METHODS: The threshold concentrations of inhaled salbutamol required for a 20%
      change in FEV(1) as PC(20), or a 35% change in specific airway conductance (sGaw)
      as PC(35) were measured in 22 persons exposed to chemical warfare and 15 normal
      control subjects. RESULTS: In 11 of the 22 subjects PC(20) salbutamol could be
      measured and in 15 of the 22 subjects PC(35) salbutamol could be measured. This
      group of patients was the responder group (PC(20) = 10.79 and PC(35) = 8.55 mg/L)
      and in them the concentration of salbutamol needed for a response was
      significantly lower than that required in normal controls (PC(20) = 237.68 and
      PC(35) = 88.72 mg/L, P < 0.001). There was a significant correlation between
      FEV(1) and PC(20) salbutamol (r = 0.815, P < 0.001). CONCLUSIONS: These results
      showed increased airway responsiveness to salbutamol in most subjects exposed to
      chemical warfare; this was correlated with airway calibre.

PMID- 18339032
TI  - Effect of vitamin E and selenium supplementation on oxidative stress status in
      pulmonary tuberculosis patients.
AB  - BACKGROUND AND OBJECTIVE: Increased production of reactive oxygen species
      secondary to phagocyte respiratory burst occurs in pulmonary tuberculosis (TB).
      The present study evaluated the efficacy of vitamin E-selenium supplementation on
      oxidative stress in newly diagnosed patients treated for pulmonary TB. METHODS: A
      double-blind, placebo-controlled trial including patients with newly diagnosed TB
      was conducted. The intervention group (n = 17) received vitamin E and selenium
      (vitamin E: 140 mg alpha-tocopherol and selenium: 200 microg) and the control
      group (n = 18) received placebo. Both groups received standard anti-TB treatment.
      Assessment of micronutrient levels, oxidative markers and total antioxidant
      capacity were carried out at baseline and 2 months after the intervention.
      RESULTS: Malondialdehyde levels were significantly reduced in the intervention
      group (P = 0.01), while there was minimal reduction in the control group. The
      mean plasma level of total antioxidants was increased significantly (P = 0.001)
      in both the intervention and the control groups. CONCLUSION: A 2-month
      intervention with vitamin E and selenium supplementation reduces oxidative stress
      and enhances total antioxidant status in patients with pulmonary TB treated with
      standard chemotherapy.

PMID- 18339033
TI  - Evaluation of enzyme-linked immunosorbent assay for Chlamydophila pneumoniae
      specific immunoglobulin M in acute respiratory tract infection.
AB  - BACKGROUND AND OBJECTIVE: The study evaluated a newly developed ELISA (Hitazyme
      Chlamydophila pneumoniae) for detecting anti-C. pneumoniae-specific IgM antibody,
      by comparing the ELISA assay to a microimmunofluorescence (MIF) test and
      immunoblotting. METHODS: One hundred patients with acute respiratory tract
      infections (58 children and 42 adults) were enrolled in the study. Paired sera
      were obtained from all subjects for serological testing of C. pneumoniae.
      RESULTS: C. pneumoniae IgM positivity was observed in 36 (62.0%) children and 11
      (26.1%) adults. However, MIF test or immunoblot revealed only four positive
      reactions in these patients. These four IgM-positive patients were also positive
      by ELISA. A significant increase in IgG and/or IgA antibody titres in paired sera
      was observed in three of the four patients. Of the remaining 96 patients, no
      significant increase in IgG or IgA antibody titre in the paired sera was
      observed. To confirm the positive reactivity of ELISA, positive sera were also
      analysed by recombinant enzyme immunoassay. Forty-three cases that were IgM
      positive only by ELISA were all negative by recombinant enzyme immunoassay and
      the ELISA results were considered to be false-positives. CONCLUSIONS: These
      results indicate that a newly developed ELISA for detecting anti-C. pneumoniae
      specific IgM antibody frequently generates false-positive findings in patients
      with acute respiratory tract infections, at the current cut-off level. Further
      studies are needed to determine an appropriate cut-off level and the possible
      causes of the false-positive results in the ELISA.

PMID- 18339034
TI  - Symptomatic ocular metastases in lung cancer.
AB  - BACKGROUND AND OBJECTIVE: A survey was carried out of ocular manifestations of
      lung cancer. METHODS: A retrospective analysis was performed of all lung cancer
      patients diagnosed between 1991 and 2005 at Taipei Veterans General Hospital,
      Taipei, Taiwan. RESULTS: Sixteen lung cancer patients with symptomatic ocular
      metastases were identified. The incidence was less than 1%. The low incidence
      among these patients contrasts with previous reports of an incidence of about 6
      7%, and suggests that most patients with ocular metastasis may be asymptomatic
      and remain undiagnosed. The most frequent ocular symptoms were changes in visual
      acuity. Metastases most frequently originated from adenocarcinomas and the
      choroids were the most common sites of metastases. Ten of the 16 ocular
      metastases were early events, identified prior to or at the initial diagnosis of
      the lung cancer. Only three of the 16 ocular metastatic events presented as
      solitary distant metastases. CONCLUSION: Although symptomatic ocular metastases
      are rare, they should be considered in lung cancer patients presenting with
      alterations in visual acuity.

PMID- 18339035
TI  - 'Fungal soup': Report of two cases of tumour-like blocked pulmonary cavities with
      liquid content infected with aspergilli, a rare form of pulmonary aspergillosis.
AB  - Two cases of a rare and uncommonly described form of Aspergillus lung disease
      were diagnosed from incidental CXR abnormalities. This strange presentation has
      been described in the literature as 'tumour-like blocked pulmonary cavities with
      liquid content infected by aspergilli'. The details of these two cases are
      reported together with a discussion of the diagnostic features of the disease and
      its position in the spectrum of pulmonary diseases caused by Aspergillus.

PMID- 18339036
TI  - Survival of a patient with pulmonary Cunninghamella bertholletiae infection
      without surgical intervention.
AB  - Mucormycosis is an uncommon fungal infection, which generally develops in
      immunosuppressed hosts. In particular, pulmonary infection by Cunninghamella
      bertholletiae, a rare species of Mucor, is characterized by invasiveness and high
      mortality. Herein a case of pulmonary mucormycosis due to C. bertholletiae in a
      female patient with chronic renal insufficiency, secondary to microscopic
      polyarteritis, is reported. The patient survived after successful treatment with
      a cumulative dose of 1508 mg of amphotericin B, phased reduction of
      glucocorticoid therapy and chest tube drainage of a pneumothorax, without the
      necessity for surgical intervention. This case demonstrates that conservative
      therapy may be effective in patients for whom surgical intervention is not an
      option.

PMID- 18339037
TI  - Pulmonary mucormycosis (Cunninghamella bertholletiae) with cavitation diagnosed
      using ultra-thin fibre-optic bronchoscopy.
AB  - Recently, ultra-thin bronchoscopy has made it possible to observe smaller bronchi
      not visualized using standard techniques. We describe a case of pulmonary
      mucormycosis with cavitation, diagnosed using an ultra-thin bronchoscope. A 15
      year-old girl with acute myeloid leukaemia had taken oral prednisolone, 60
      mg/day, for graft versus host disease after haematopoietic stem cell
      transplantation. She was admitted to our hospital with fever and a large cavitary
      lesion in the right hilum. Using an ultra-thin bronchoscope, the interior of the
      cavity in the superior segment of the right lower lobe was observed. The
      bronchoscopic findings revealed debris adhering to the cavity wall with a small
      volume of effusion. Cunninghamella bertholletiae was isolated from the effusion
      specimen obtained using the bronchoscope. Pulmonary mucormycosis (C.
      bertholletiae) complicating an immunocompromised state was diagnosed. Ultra-thin
      bronchoscopy is useful to diagnose complex pulmonary infections and more research
      is needed to verify its clinical indications and utility.

PMID- 18339038
TI  - Endobronchial ultrasound morphology of expiratory central airway collapse.
AB  - Differences in central airway wall structure in patients with various forms of
      expiratory central airway collapse can be identified by endobronchial ultrasound
      using a 20 MHz radial probe. In tracheobronchomalacia due to relapsing
      polychondritis, the cartilage is thick and irregular while the membranous portion
      is normal. In malacia due to chronic inflammation after tracheotomy, the
      cartilage is thick and irregular and the membranous portion is also thick. In
      excessive dynamic airway collapse associated with COPD, on the contrary, the
      cartilage is normal and the posterior membrane is thin when compared to the
      normal airway wall structures identified in a patient with physiological dynamic
      airway collapse. These findings may support the hypothesis that various clinical
      forms of expiratory central airway collapse are not only different
      morphologically, physiologically and aetiologically, but also structurally.

PMID- 18339040
TI  - Rupatadine in allergic rhinitis and chronic urticaria.
AB  - Histamine is the primary mediator involved the pathophysiology of allergic
      rhinitis and chronic urticaria, and this explains the prominent role that
      histamine H(1)-receptor antagonists have in the treatment of these disorders.
      However, histamine is clearly not the only mediator involved in the inflammatory
      cascade. There is an emerging view that drugs which can inhibit a broader range
      of inflammatory processes may prove to be more effective in providing symptomatic
      relief in both allergic rhinitis and chronic urticaria. This is an important
      consideration of the Allergic Rhinitis and its Impact on Asthma (ARIA) initiative
      which provides a scientific basis for defining what are the desirable properties
      of an 'ideal' antihistamine. In this review of rupatadine, a newer dual inhibitor
      of histamine H(1)- and PAF-receptors, we evaluate the evidence for a mechanism of
      action which includes anti-inflammatory effects in addition to a powerful
      inhibition of H(1)- and PAF-receptors. We assess this in relation to the clinical
      efficacy (particularly the speed of onset of action) and safety of rupatadine,
      and importantly its longer term utility in everyday life. In clinical trials,
      rupatadine has been shown to be an effective and well-tolerated treatment for
      allergic rhinitis and chronic idiopathic urticaria (CIU). It has a fast onset of
      action, producing rapid symptomatic relief, and it also has an extended duration
      of clinical activity which allows once-daily administration. In comparative
      clinical trials rupatadine was shown to be at least as effective as drugs such as
      loratadine, cetirizine, desloratadine and ebastine in reducing allergic symptoms
      in adult/adolescent patients with seasonal, perennial or persistent allergic
      rhinitis. Importantly, rupatadine demonstrated no adverse cardiovascular effects
      in preclinical or extensive clinical testing, nor negative significant effects on
      cognition or psychomotor performance (including a practical driving study). It
      improved the overall well-being of patients with allergic rhinitis or CIU based
      on findings from quality of life questionnaires and patient global rating scores
      in clinical trials. Thus, rupatadine is a recently introduced dual inhibitor of
      histamine H(1)- and PAF-receptors, which has been shown to be an effective and
      generally well-tolerated treatment for allergic rhinitis and chronic urticaria.
      It possesses a broader profile of anti-inflammatory properties inhibiting both
      inflammatory cells and a range of mediators involved in the early- and late-phase
      inflammatory response, but the clinical relevance of these effects remain to be
      clarified.

PMID- 18339041
TI  - Nearwork-induced transient myopia (NITM) and permanent myopia--is there a link?
AB  - Myopia is a worldwide public health problem. However, its understanding is
      incomplete, and many of its preventative and therapeutic aspects remain
      controversial. Nearwork is a primary, environmentally based factor in the
      aetiology of permanent myopia (PM), with nearwork-induced transient myopia (NITM)
      being a possible contributory component. A relationship between PM and NITM has
      been suggested, but that connection has remained somewhat indirect and elusive.
      However, based on recent converging evidence from clinical, laboratory and
      modelling studies, a five-fold argument will be advanced for a possible link
      between PM and NITM.

PMID- 18339042
TI  - Gender differences in early accommodation and vergence development.
AB  - A remote haploscopic photorefractor was used to assess objective binocular
      vergence and accommodation responses in 157 full-term healthy infants aged 1-6
      months while fixating a brightly coloured target moving between fixation
      distances at 2, 1, 0.5 and 0.33 m. Vergence and accommodation response gain
      matured rapidly from 'flat' neonatal responses at an intercept of approximately 2
      dioptres (D) for accommodation and 2.5 metre angles(MA) for vergence, reaching
      adult-like values at 4 months. Vergence gain was marginally higher in females (p
      = 0.064), but accommodation gain (p = 0.034) was higher and accommodative
      intercept closer to zero (p = 0.004) in males in the first 3 months as they
      relaxed accommodation more appropriately for distant targets. More females showed
      flat accommodation responses (p = 0.029). More males behaved hypermetropically in
      the first two months of life, but when these hypermetropic infants were excluded
      from the analysis, the gender difference remained. Gender differences disappeared
      after three months. Data showed variable responses and infants could behave
      appropriately and simultaneously on both, neither or only one measure at all
      ages. If accommodation was appropriate (gain between 0.7 and 1.3; r(2) > 0.7) but
      vergence was not, males over- and under-converged equally, while the females who
      accommodated appropriately were more likely to overconverge (p = 0.008). The
      apparent earlier maturity of the male accommodative responses may be due to
      refractive error differences but could also reflect gender-specific male
      preference for blur cues while females show earlier preference for disparity,
      which may underpin the earlier emerging, disparity dependent, stereopsis and full
      vergence found in females in other studies.

PMID- 18339043
TI  - Changes in corneal sensitivity and tear physiology after phacoemulsification.
AB  - PURPOSE: To identify any changes in corneal sensitivity and tear physiology after
      phacoemulsification and to evaluate the effectiveness of the use of ophthalmic
      lubricants. METHODS: The design of the study was longitudinal, parallel,
      randomised and double masked. Eighteen patients (average age 70.83 +/- 10.66
      years, 7 males and 11 females) undergoing phacoemulsification were recruited and
      divided into three groups of six. In addition to the prednisolone acetate 1% and
      chloramphenicol 0.5% routinely given to patients postoperatively, the first two
      groups were given a tear lubricant (Refresh Soothe and Protect, Allergan Inc.,
      Irvine, CA, USA) and saline (Chauvin Pharmaceuticals Ltd, Essex, UK),
      respectively, and the third was a control group and did not receive any
      additional eye drops. Tear production, evaporation, lipid layer interferometry
      and osmolarity along with corneal sensitivity were measured before and 3 days, 2
      weeks, 1 month and 3 months after the surgery. RESULTS: Statistically significant
      detrimental changes were seen in all parameters of corneal sensitivity and tear
      physiology immediately after phacoemulsification. Tear physiology recovered
      within 1 month. Corneal sensitivity did not return to normal levels in 3 months,
      but a trend towards full recovery was seen. Saline and the tear lubricant were
      not found to have an effect on the improvement of tear physiology and corneal
      sensitivity post-surgically. CONCLUSIONS: Deterioration in corneal sensitivity
      and tear physiology is seen immediately after phacoemulsification. Corneal
      sensitivity does not return to preoperative levels until 3 months postoperatively
      whereas the tear functions recover within 1 month.

PMID- 18339044
TI  - The effects of monocular refractive blur on gait parameters when negotiating a
      raised surface.
AB  - Falls in the elderly are a major cause of mortality and morbidity. Elderly people
      with visual impairment have been found to be at increased risk of falling, with
      poor visual acuity in one eye causing greater risk than poor binocular visual
      acuity. The present study investigated whether monocular refractive blur, at a
      level typically used for monovision correction, would significantly reduce
      stereoacuity and consequently affect gait parameters when negotiating a raised
      surface. Fourteen healthy subjects (25.8 +/- 5.6 years) walked up to and on to a
      raised surface, under four visual conditions; binocular, +2DS blur over their non
      dominant eye, +2DS blur over their dominant eye and with their dominant eye
      occluded. Analysis focussed on foot positioning and toe clearance parameters.
      Monocular blur had no effect on binocular acuity, but caused a small decline in
      binocular contrast sensitivity and a large decline in stereoacuity (p < 0.01).
      Vertical toe clearance increased under monocular blur or occlusion (p < 0.01)
      with a significantly greater increase under blur of the dominant eye compared
      with blur of the non-dominant eye (p < 0.01). Increase in toe clearance was
      facilitated by increasing maximum toe elevation (p < 0.01). Findings indicate
      that monocular blur at a level typically used for monovision correction
      significantly reduced stereoacuity and consequently the ability to accurately
      perceive the height and position of a raised surface placed within the travel
      path. These findings may help explain why elderly individuals with poor visual
      acuity in one eye have been found to have an increased risk of falling.

PMID- 18339045
TI  - Reproducibility of sphero-cylindrical prescriptions.
AB  - PURPOSE: To investigate the reproducibility of the sphero-cylindrical
      prescriptions provided by 40 optometrists. METHODS: Forty registered optometrists
      were randomly selected from the cities of Oxford and Westminster in the UK to
      perform a sphero-cylindrical refraction on an asymptomatic 29-year-old male
      subject. The 95% limits of reproducibility for each component of refraction were
      assessed and are presented together with scatterplots, distribution ellipsoids
      and polar profiles of dioptric power. RESULTS: The mean stigmatic (spherical
      equivalent) refraction for the right eye was -0.83 D (S.D. = 0.28 D) with 95%
      limits of agreement -1.38 and -0.28 D. The 95% reproducibility limits for
      stigmatic data [1.96(square root of 2) (S.D.)] was 0.78 D. The average inter
      ocular difference in the stigmatic components of refraction was -0.044 D (S.D. =
      0.20 D) but estimates ranged from -0.50 to +0.50 D. Mean ortho- and oblique
      antistigmatic refractions were -0.23 D (S.D. = 0.084 D) and -0.14 D (S.D. = 0.086
      D) respectively. CONCLUSIONS: The findings of this paper suggest that refractions
      performed by multiple optometrists on a single eye will differ in their stigmatic
      component by over 0.78 D on average not more than once in 20 refractions. The
      reproducibility of refractions reported here, approximately twice as variable as
      those reported under repeatability conditions, has profound implications for the
      analysis of refractive data collected by multiple optometrists over the course of
      replication, longitudinal and epidemiological studies.

PMID- 18339046
TI  - Effect of sport-tinted contact lenses for contrast enhancement on retinal
      straylight measurements.
AB  - PURPOSE: To investigate the effect of two tinted contact lenses (CL) designed for
      outdoor sports activity on the psychometric determination of retinal straylight
      using the compensation comparison method. METHODS: Thirteen emmetropic subjects
      were randomly fitted with two different tinted Nike Maxsight (Bausch & Lomb,
      Rochester, NY, USA) CL in one eye, while the contralateral eye was fitted with a
      clear lens made of the same material (Optima 38, Bausch & Lomb). Three valid
      straylight measurements were taken on each eye before and a few minutes after
      lens insertion, when lens stabilization had occurred. RESULTS: The subjects' mean
      straylight values were 0.90 +/- 0.09 at baseline and 0.95 +/- 0.10 with the clear
      Optima 38 CL. Straylight values were 0.97 +/- 0.10 and 1.0 +/- 0.10 log units
      with the amber and grey-green tinted CL, respectively. Differences in straylight
      between baseline (without CL) and with the clear CL in place were neither
      statistically significant (p = 0.066) nor was there a significant difference
      between baseline and the amber CL (p = 0.052). However, the grey-green CL showed
      a statistically significant difference from baseline (p = 0.006). Differences in
      straylight with the clear CL compared with the grey-green CL were also
      statistically different from zero (p = 0.002) showing an increased straylight
      value for the tinted CL. These differences were variable, but consistent for each
      subject, thus those showing higher or lower changes with one tinted lens tended
      to show the same trend with the second lens (r(2) = 0.736). CONCLUSIONS: Despite
      increases having been found in straylight values with tinted contact lenses,
      those changes are not likely to induce clinically significant changes in visual
      function under photopic conditions, even for the grey-green CL, which seems to
      increase straylight values more significantly than the amber CL. This difference
      between the tinted CL could suggest a wavelength dependence of straylight values,
      although this should be investigated further by controlling for pupil size and
      subjects' pigmentation, as well as by using neutral density filters.

PMID- 18339047
TI  - Vertical imbalance induced by prism-ballasted soft toric contact lenses fitted
      unilaterally.
AB  - Fitting a prism-ballasted soft toric contact lens unilaterally may potentially
      induce a vergence error that the subject cannot compensate. In the present study,
      a prism-ballasted (1.5Delta base down) soft toric contact lens was fitted in the
      right eye only of 10 subjects with normal binocular vision. The effect on
      binocular vision was evaluated by measuring vertical phoria adaptation and
      vertical fixation disparity adaptation. The results show that the vertical
      vergence error induced was well compensated and fully adapted to. However, care
      might be needed when fitting these lenses unilaterally in subjects with vertical
      phoria-related problems.

PMID- 18339048
TI  - Clinical and experimental findings in Acanthamoeba keratitis with Heidelberg
      Retina Tomograph III-RCM.
AB  - PURPOSE: To observe Acanthamoeba cysts and trophozoites in the corneal tissue of
      patients and rabbits with Acanthamoeba keratitis (AK), using the Heidelberg
      Retina Tomograph III Rostock-cornea-module (HRTIII-RCM). METHODS: Eight eyes of
      seven patients with clinical and laboratory diagnosis of AK, presenting to the
      Beijing Institute of Ophthalmology between July and December 2006, were included
      in this study. The laboratory diagnosis in all cases was established by a
      cytological analysis and culture of the corneal scraping. The scanning with
      HRTIII-RCM was performed on all the patients. Acanthamoeba cysts and trophozoites
      in the corneas of three rabbits were observed with the HRTIII-RCM after a
      suspension of trophozoites was injected into the corneal stromal layer of the
      rabbits. RESULTS: Acanthamoeba cysts or trophozoites were observed with the
      HRTIII-RCM in the corneas of all the patients. The size and shape of Acanthamoeba
      in the tissue of the rabbit corneas was consistent with that in the patients'
      eyes. The Acanthamoeba cyst presented a round high-contrast particle, 15-20
      microm in diameter, with a double wall. In contrast, the trophozoite presented an
      irregular high-contrast particle, without an apparent wall, 25-40 microm in
      diameter and with a round conspicuous nucleus. CONCLUSIONS: HRTIII-RCM is a
      useful non-invasive clinical technique to help to diagnose and monitor the
      response of AK to therapy.

PMID- 18339049
TI  - Use of multiple preferred retinal loci in Stargardt's disease during natural
      tasks: a case study.
AB  - Individuals with central visual field loss often use a preferred retinal locus
      (PRL) to compensate for their deficit. We present a case study examining the eye
      movements of a subject with Stargardt's disease causing bilateral central
      scotomas, while performing a set of natural tasks including: making a sandwich;
      building a model; reaching and grasping; and catching a ball. In general, the
      subject preferred to use PRLs in the lower left visual field. However, there was
      considerable variation in the location and extent of the PRLs used. Our results
      demonstrate that a well-defined PRL is not necessary to adequately perform this
      set of tasks and that many sites in the peripheral retina may be viable for PRLs,
      contingent on task and stimulus constraints.

PMID- 18339050
TI  - Mixed messages.

PMID- 18339051
TI  - Calcium intake and its relationship with adiposity and insulin resistance in post
      pubertal adolescents.
AB  - BACKGROUND: Dietary calcium intake has been described as being a negative
      contributor to adiposity. In adolescents, this relationship is not well
      established. The objectives of the present study were to compare the calcium
      intake of normal-weight and obese adolescents and to evaluate its relationship
      with adiposity and insulin resistance. METHODS: A cross-sectional analysis of 96
      post-pubertal adolescents; 47 normal weight and 49 obese, mean age 16.6 (SD +/-
      1.3) years. Body composition was assessed by dual-energy X-ray absorptiometry.
      Dietary intake was evaluated using a 3-day dietary record. The biochemical
      evaluation comprised the measurements of serum lipids, lipoproteins, glucose and
      insulin. Insulin resistance was calculated using the Homeostasis Model Assessment
      of Insulin resistance (HOMA-IR). RESULTS: The mean calcium intake, adjusted for
      energy, was lower in obese adolescents, 585.2 (+/-249.9) mg, than in normal
      weight adolescents, 692.1 (+/-199.5) mg. Only 4% of adolescents had an adequate
      intake of calcium. Calcium intake was inversely associated with body trunk fat,
      insulin and HOMA-IR in the obese group. The quartile analysis of calcium intake
      provided evidence that girls in the highest quartile had decreased adiposity and
      insulin resistance. CONCLUSIONS: This study showed a negative relationship
      between calcium intake and body fat and insulin resistance, mainly in obese
      girls, and demonstrates the importance of an increased dietary calcium intake.

PMID- 18339052
TI  - Cardiovascular disease-risk factors in middle-aged osteopaenic women treated with
      calcium alone or combined to three nutrients essential to artery and bone
      collagen.
AB  - BACKGROUND: Recent research suggests that cardiovascular disease (CVD) and bone
      loss are functionally interwoven. This study examined the concomitant effects of
      a nutritional treatment of osteopaenia on CVD-risk factors. METHODS: A 1-year
      placebo-controlled trial was conducted on middle-aged women with normal (group A)
      or low (groups B and C) bone mineral density. Subjects (n = 20 per group) took
      daily either a placebo, calcium carbonate alone or combined to a vitamin (C and
      B(6))-proline capsule, respectively. Urinary pyridoxic acid (used to assess
      treatment compliance), plasma homocysteine, serum lipids and lipoproteins were
      measured before and after nutritional intervention. RESULTS: Groups were
      comparable at baseline in most parameters of interest. No changes occurred in
      groups A and B. The 4%, 7% and 25% reductions of total cholesterol, LDL and
      triglycerides, and 14% elevation of HDL were all significant in group C. A trend
      toward reduction was observed for homocysteine in this group. CONCLUSIONS:
      Vitamins C (500 mg) and B(6) (75 mg) combined with proline had consistent
      beneficial effects on CVD-risk factors, whereas calcium alone did not. This study
      also underlined the importance of considering vitamin B(6) status as a potential
      CVD risk factor.

PMID- 18339053
TI  - The association between cheese consumption and cardiovascular risk factors among
      adults.
AB  - BACKGROUND: Although current dietary guidelines recommend limiting foods high in
      fat and saturated fat, such as high-fat dairy, the effect of cheese consumption
      on body composition and cardiovascular risk factors is largely unknown. METHODS:
      Participants from a US population-based survey, NHANES III, aged 25-75 years who
      completed a food frequency questionnaire and had measures of body composition and
      cardiovascular risk factors were included (n = 10 872). Linear regression was
      used to compare anthropometrics, blood lipids, blood pressure and blood glucose
      across categories of cheese consumption (combined full and low-fat). RESULTS: In
      women, more frequent cheese consumption was associated with higher HDL-C and
      lower LDL-C (p for trend, < 0.05). However, in men, more frequent cheese
      consumption was associated with a higher body mass index (BMI), waist
      circumference, HDL-C and LDL-C, and diastolic blood pressure (p for trend, <
      0.05). Men consuming 30 + servings/month had significantly higher BMI, waist
      circumference, and diastolic blood pressure compared to nonconsumers (P < 0.05).
      CONCLUSIONS: More frequent cheese consumption was associated with less favourable
      body composition and cardiovascular risk profile in men, but with a more
      favourable cardiovascular risk profile in women. However, the type of cheese
      consumed by men and women may have differed resulting in opposing trends on body
      composition and cardiovascular risk factors.

PMID- 18339054
TI  - Dietary intervention in chronic fatigue syndrome.
AB  - BACKGROUND: Anecdotal reports and books have been published linking an over
      growth of Candida Albicans with chronic fatigue syndrome (CFS), suggesting
      dietary change as a treatment option. Little scientific data has been published
      to validate this controversial theory. This study aims to determine the efficacy
      of dietary intervention on level of fatigue and quality of life (QoL) in
      individuals with CFS. METHODS: A 24-week randomized intervention study was
      conducted with 52 individuals diagnosed with CFS. Patients were randomized to
      either a low sugar low yeast (LSLY) or healthy eating (HE) dietary interventions.
      Primary outcome measures were fatigue as measured by the Chalder Fatigue Score
      and QoL measured by Medical Outcomes Survey Short Form-36. RESULTS: A high drop
      out rate occurred with 13 participants not completing the final evaluation
      (7HE/6LSLY). Intention to treat analysis showed no statistically significant
      differences on primary outcome measurements. CONCLUSION: In this randomized
      control trial, a LSLY diet appeared to be no more efficacious on levels of
      fatigue or QoL compared to HE. Given the difficulty with dietary compliance
      experienced by participants, especially in the LSLY group, it would appear HE
      guidance is a more pragmatic approach than advocating a complicated dietary
      regime.

PMID- 18339055
TI  - Assessing dietary patterns in Barbados highlights the need for nutritional
      intervention to reduce risk of chronic disease.
AB  - BACKGROUND: The dietary habits of the Caribbean have been changing to include
      more fast foods and a less nutrient dense diet. The aims of this study are to
      examine dietary patterns in Barbados and highlight foods for a nutritional
      intervention. METHODS: Four-day food diaries collected from control participants
      in the population-based, case-control Barbados National Cancer Study (BNCS).
      RESULTS: Forty-nine adult participants (91% response) completed the diaries
      providing 191 days of dietary data. Total energy intake was almost identical to
      data collected 5-years earlier in the Barbados Food Consumption and
      Anthropometric Survey 2000, but the percent energy derived from fat was from 2.1%
      to 5.2% higher. Sugar intake exceeded the Caribbean recommendation almost four
      fold, while intakes of calcium, iron (women only), zinc and dietary fibre were
      below recommendations. Fish and chicken dishes were the two largest sources of
      energy and fat. Sweetened drinks and juices provided over 40% of total sugar
      intake. CONCLUSIONS: These data provide existing dietary patterns and strongly
      justify a nutritional intervention program to reduce dietary risk factors for
      chronic disease. The intervention could focus on the specific foods highlighted,
      both regarding frequency and amount of consumption. Effectiveness can be
      evaluated pre- and post-intervention using our Food Frequency Questionnaire
      developed for BNCS.

PMID- 18339056
TI  - Habitual caffeine intake in women of childbearing age.
AB  - BACKGROUND: For women, delayed conception and recurrent pregnant loss are just a
      few of the health implications associated with a caffeine-rich diet (Mol. Hum.
      Reprod., 11, 357). At present there is a deficit of prospective research
      measuring current habitual intakes of caffeine in UK women. The purpose of the
      current study was to collect up-to-date baseline data to assess caffeine intake
      and knowledge in a group of women (aged 16-45 years). METHODS: Seventy Caucasian
      subjects (mean age 30.4 +/- 8.7 years) were recruited from business offices
      within the Manchester area. Each participant completed a 3-day food diary and
      lifestyle questionnaire. RESULTS: The mean intake of caffeine was 173.95 mg day(
      1) (+/-128.39 mg day(-1)). Eighteen per cent of subjects exceeded caffeine
      guidelines and consumed 300 mg caffeine or more each day. Subjects consuming over
      300 mg day(-1) were more likely to be older (P = 0.016) and smokers (P = 0.000).
      Individuals given previous advice about caffeine and health, had lower intakes (P
      = 0.002). CONCLUSIONS: Many women are unaware of health perturbations associated
      with caffeine consumption. A diet abundant in caffeine may result in delayed
      conception, infertility and increased risk of osteoporosis, cardiovascular
      disease and cancer later in life. Such information needs to be conveyed to the
      public sector. Future research is also required to devise specific caffeine
      guidelines, particularly safe upper limits.

PMID- 18339057
TI  - Nutrition support in major burn injury: case analysis of dietetic activity,
      resource use and cost implications.
AB  - BACKGROUND: Patients with major burn injury are among the most catabolic and
      nutritionally vulnerable of all hospital admissions. A considerable amount of
      dietetic intervention is often required. To date, UK practice has not been
      described in detail. This study aimed to identify nutritional interventions,
      resource use and associated costs for a typical patient admitted with major
      burns. METHODS: A 28-year-old male with 43.5% total body surface area flame
      injury was selected for study. Dietetic, medical and pharmacy records were
      reviewed for data regarding nutritional status, interventions and product use.
      Costs of dietetic staffing, nutrition support products, related ancillary items
      and hospital food provision were calculated. RESULTS: The patient required 68
      days of nutrition support, including 40 days of nasogastric tube feeding. Seventy
      per cent of bedside reviews resulted in dietetic intervention. Initiation of
      nutrition support, substrate use, and frequency of biochemical and weight
      monitoring were largely in compliance with practice guidelines. Overall cost of
      nutritional care for the inpatient episode was pound 1377. CONCLUSION: Work is
      now required to assess current nutrition practices across different UK centres
      and for a range of burn severities, to establish a baseline from which resource
      and financial requirements can ultimately be developed.

PMID- 18339059
TI  - Re: A comparison of some of the cardiovascular risk factors in vegetarian and
      omnivorous Turkish females.

PMID- 18339061
TI  - Obesity: a global problem.

PMID- 18339064
TI  - Remuneration of blood donors: new proof of the pudding?

PMID- 18339065
TI  - Selling blood vs. donating blood.

PMID- 18339066
TI  - How to write a paper: an editor's tips.

PMID- 18339067
TI  - Quiet reflection after effective action: hepatitis B viraemia and hepatocellular
      carcinoma recurrence.

PMID- 18339068
TI  - Celiac disease-related autoantibodies in end-stage autoimmune liver diseases:
      what is the message?

PMID- 18339069
TI  - Depression in chronic hepatitis: the virus, the drug, or the ethnic background?

PMID- 18339070
TI  - Junctional structures and hepatocellular carcinoma: from the lab to the clinic?

PMID- 18339071
TI  - Molecular bases of the fetal liver-placenta-maternal liver excretory pathway for
      cholephilic compounds.
AB  - Potentially toxic endogenous compounds, such as bile acids (BAs) and biliary
      pigments, as well as many xenobiotics, such as drugs and food components, are
      biotransformed and eliminated by the hepatobiliary system with the collaboration
      of the kidney. However, the situation is very different during pregnancy because
      the fetal liver produces biliary compounds despite the fact that this organ,
      owing to its immaturity, is not able to eliminate them into bile. Moreover, the
      excretory ability of the fetal kidneys is also very limited. Thus, during the
      intra-uterine life, the major route to eliminate fetal BAs and biliary pigments
      is their transfer to the mother across the placenta. The maternal liver and, to a
      lesser extent, the maternal kidney, are then in charge of their biotransformation
      and elimination into faeces and urine respectively. This review describes current
      knowledge of the machinery responsible for the detoxification and excretion of
      cholephilic compounds through the pathway formed by the fetal liver-placenta
      maternal liver trio.

PMID- 18339072
TI  - Budd-Chiari syndrome: illustrated review of current management.
AB  - Budd-Chiari syndrome (BCS) is characterized by hepatic venous outflow obstruction
      at any level from the small hepatic veins to the atriocaval junction. BCS is a
      complex disease with a wide spectrum of aetiologies and presentations. This
      article reviews the current literature with respect to presentation, management
      and prognosis of the disease. Medical, interventional and surgical management of
      BCS is discussed. Particular attention is paid to interventional and surgical
      aspects of management. The review is augmented by images, which provide a
      clinical corollary to the text.

PMID- 18339073
TI  - Celiac disease autoantibodies in severe autoimmune liver disease and the effect
      of liver transplantation.
AB  - BACKGROUND/AIMS: Celiac disease (CD) is associated with primary biliary
      cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We
      investigated the following: (i) the prevalence of tissue transglutaminase
      antibodies (tTGAs) and endomysial antibodies (EMAs) in end-stage autoimmune liver
      disease (ESALD), (ii) the correlation among auto-antibodies and the human
      leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation
      on antibody kinetics. METHODS: Pretransplantation sera from 488 patients (310
      with ESALD, and 178 with non-autoimmune disease) were tested for tTGAs. Positive
      samples were also tested for EMAs, and retested 6-12 and > or = 24 months post
      transplantation. Results were correlated with the HLA type of the recipient.
      RESULTS: Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non
      autoimmune) of the patients (five-fold increased risk in ESALD). The prevalence
      of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was
      significantly higher in patients with the HLA-DQ2 or HLA-DQ8 haplotypes. tTGAs
      and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post
      transplantation. Post-transplantation, of the five patients with symptoms of
      'classical' CD, three improved. Intestinal lymphoma was diagnosed in another two
      cases with clinically 'silent' CD. CONCLUSIONS: Patients with ESALD, especially
      those who are HLA-DQ2 or HLA-DQ8 positive had a high prevalence of CD-associated
      antibodies. Both tTGAs and EMAs decreased post-transplantation without gluten
      withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent
      progression to intestinal lymphoma.

PMID- 18339074
TI  - Comparing the safety, tolerability and quality of life in patients with chronic
      hepatitis B vs chronic hepatitis C treated with peginterferon alpha-2a.
AB  - BACKGROUND/AIMS: Hepatitis B and C viruses (HBV and HCV) are two clinically
      distinct but related diseases. Pooled data from five studies of peginterferon
      alpha-2a in patients with chronic HCV infection (CHC) were compared with two
      studies of the drug in patients with chronic HBV infection (CHB). METHOD: The HBV
      studies included both hepatitis B e antigen (HBeAg)-positive (n=271) and HBeAg
      negative (n=177) patients; 791 patients took part in the HCV trials. In all
      studies, patients were treated with 180 microg peginterferon alpha-2a monotherapy
      once weekly for 48 weeks. The number of adverse events (AEs), discontinuations
      and dose modifications were documented. Health-related quality of life (HRQL) was
      assessed using the Short-Form 36 questionnaire. Safety was assessed throughout
      the treatment period. A 24-week treatment-free follow-up period was also
      included. RESULTS: Differences (HBV vs HCV) were observed in the incidence of AEs
      (88-89 vs 96-100%), serious AEs (4-5 vs 7-16%) and treatment withdrawals (6-8 vs
      17-33%). The frequency of depression-related events was lower in CHB patients (4
      vs 22%, P<0.001), as was the impact of treatment on HRQL. CONCLUSIONS: The safety
      and tolerability of peginterferon alpha-2a in patients with CHB compares
      favourably with that observed in CHC patients, with a lower incidence of common
      interferon-related AEs and a significantly lower incidence of depression.

PMID- 18339075
TI  - Optimized cutoffs improve performance of the aspartate aminotransferase to
      platelet ratio index for predicting significant liver fibrosis in human
      immunodeficiency virus/hepatitis C virus co-infection.
AB  - AIM: To assess the diagnostic value of modified cutoffs for aspartate
      aminotransferase to platelet ratio index (APRI) to predict significant liver
      fibrosis in human immunodeficiency virus (HIV)/hepatitis C virus (HCV) patients.
      PATIENTS AND METHODS: This retrospective cross-sectional study included
      consecutive patients with HIV/HCV co-infection who underwent percutaneous liver
      biopsy. The accuracy of APRI for the diagnosis of significant fibrosis (F2/F3/F4
      METAVIR) was evaluated by estimating the positive and negative predictive values
      (PPV and NPV respectively) and by measuring the area under the receiver operating
      characteristics curve (AUROC). RESULTS: One hundred and eleven patients were
      included (73% men, mean age 40.2+/-7.8 years). Significant fibrosis was observed
      in 45 patients (41%). To discriminate these subjects, the AUROC of APRI was
      0.774+/-0.045. An APRI > or = 1.8 showed a PPV of 75% for the presence of
      significant fibrosis, and an index < 0.6 excluded significant fibrosis with an
      NPV of 87%. If biopsy indication was based only on APRI and restricted to scores
      in the intermediate range (> or = 0.6 and < 1.8), 46% of liver biopsies could
      have been avoided as compared with 40% using the classical cutoffs. CONCLUSION:
      APRI with adjusted cutoffs can predict significant liver fibrosis in patients
      with HIV/HCV co-infection and might obviate the need to perform a biopsy in a
      considerable percentage of those subjects.

PMID- 18339076
TI  - Seropositivity for delta hepatitis in patients with chronic hepatitis B and liver
      cirrhosis in Turkey: a meta-analysis.
AB  - BACKGROUND: Recent reports suggest a decline of delta hepatitis (DH) in the West
      as well as in the Far East. AIM: To study the DH seroepidemiology in Turkey.
      METHODS: Statistical power analysis was utilized based on data available in a
      recent article using prevalence figure estimates. Binominal distribution was
      applied in order to assess the number of samples required to estimate the
      prevalence with a given precision. RESULTS: Out of 62 studies in the original
      study, 32 were eliminated because of insufficient power. A total of 6734 patients
      (5231 with chronic hepatitis and 1503 with cirrhosis) were analysed. Anti-HDV
      seropositivity among patients with chronic hepatitis B (CHB) and hepatitis B
      induced cirrhosis was lowest in the west of the country and highest in the
      southeast (5 vs. 27%, P<0.0001 and 20 vs. 46%, P<0.0001) respectively. Compared
      with data obtained before 1995, after 1995, DH prevalence in patients with CHB
      and cirrhosis decreased from 29 to 12% (P<0.0001) and from 38 to 27% (P=0.03) in
      central and southeast Turkey and from 38 to 20% (P<0.0001) and from 66 to 46%
      (P<0.002) in west and southeast Turkey respectively. CONCLUSION: Despite the
      decrease of its prevalence in Turkey, DH remains a significant health problem in
      parts of the country with low socio-economic level.

PMID- 18339077
TI  - Liver adenomatosis: re-evaluation of aetiology and management.
AB  - BACKGROUND: Liver adenomatosis (LA) is a rare benign parenchymal liver disease
      with unknown aetiology. In recent reports, LA has been associated with hepatic
      steatosis, with potential implications for the management of this disease. The
      aim of this study was to determine prognosis and optimal management of patients
      with LA. METHODS: Clinical presentation, diagnostic studies and management of
      patients with LA were analysed in our centre. Furthermore, a Medline search of
      all published case reports and series of LA patients was performed. RESULTS:
      Ninety-four patients with LA have been reported in the literature. Fifty-two per
      cent of females had a history of oral contraceptive use. Eighteen per cent of
      patients had steatosis in nontumoral tissue. In our own series, five of six
      patients had histologically confirmed steatosis. Forty-three per cent of patients
      presented with acute pain, of whom 46% had a haemorrhagical complication, in
      contrast to 2% of nonsymptomatic patients. Tumours <5 cm tended to increase in
      size during follow-up and only in four patients tumour regression was observed.
      CONCLUSION: Liver adenomatosis is a progressive, benign parenchymal disease
      mainly occurring in females. There is a potential link with hepatic steatosis
      with implications for the management of patients with LA. Noninvasive diagnosis
      is difficult because of the variety of tumoral and nontumoral components.
      Management should primarily be conservative.

PMID- 18339078
TI  - Accelerated orthotopic hepatocellular carcinomas growth is linked to increased
      expression of pro-angiogenic and prometastatic factors in murine liver fibrosis.
AB  - BACKGROUND: Most experimental therapy studies are performed in mice that bear
      subcutaneous or orthotopic hepatoma but are otherwise healthy. We questioned
      whether a pre-existing fibrosis affects tumour development of implanted syngenic
      hepatoma cells. To further investigate a selected panel of factors involved in
      tumour growth, tumour organ samples were characterized for gene expression of
      vascular endothelial growth factor (VEGF)-A/-C, VEGF receptors Flt1, Flk-1, Flt-4
      and for VEGF-A protein levels. RESULTS: The presented data show that tumour sizes
      were 3.7-fold increased and fibrotic livers had numerous satellites. Increased
      tumour sizes were associated with elevated intratumoral VEGF-A protein amounts
      and intratumoral increased VEGF receptor gene expression levels in tumour tissue
      from fibrotic livers as compared with non-fibrotic livers. Additionally,
      intratumoral gene expression levels of matrix metalloproteinase-2 (MMP-2) and MMP
      9 were elevated in fibrotic mice. CONCLUSION: Our results indicate that liver
      fibrosis stimulates tumour development of implanted syngenic hepatoma cells.
      Accelerated tumour growth was going along with elevated intratumoral VEGF-A and
      VEGF-A receptor status, which most probably mediated pro-angiogenic and
      prometastatic effects in this model. Furthermore, advanced tumour spread was
      associated with increased MMP-2/-9 expression. These data suggest that the
      intratumoral VEGF-A proteins levels and VEGF receptor status contribute to
      accelerated hepatocellular carcinoma development in fibrotic mice and that
      elevated MMP-2, MMP-9 and VEGF-C levels could promote tumour metastasis in this
      model.

PMID- 18339079
TI  - A three-dimensional anatomy model of the liver organ using a gloved hand.

PMID- 18339080
TI  - Atorvastatin induces apoptosis by a caspase-9-dependent pathway: an in vitro
      study on activated rat hepatic stellate cells.
AB  - BACKGROUND: Statins are shown to have cholesterol-independent properties such as
      anti-inflammation and immunomodulation. Activated hepatic stellate cells (HSCs)
      acquire the capacity to synthesize matrix proteins in damaged liver. We tested
      the hypothesis that atorvastatin may be capable of inducing apoptosis in HSCs.
      METHODS: Primary cultures of rat HSCs were exposed to atorvastatin, mevalonic
      acid and U0126. Quantification of living, apoptotic and necrotic HSCs was
      performed by flow cytometry and laser-scan microscopy. Cell-cycle analysis was
      performed by flow cytometry. Pro- and anti-apoptotic factors were investigated by
      Western blot and electrophoresis mobility shift assay. Protease activity of
      caspases was calculated using a colorimetric kit. RESULTS: Atorvastatin leads to
      a G2-arrest and induces apoptosis in activated HSCs. Atorvastatin-mediated
      apoptosis could be blocked by co-administration of mevalonic acid and U0126. No
      effects of atorvastatin on gene expression of CD95, CD95L, NF-kappaB, p53 and
      p21WAF1 could be observed. Atorvastatin-induced apoptosis in activated HSCs is
      related to an increased protease activity of caspase-9 and -3. Gene expression of
      the major proteins of the bcl-system shows that truncated Bid is involved in
      apoptosis mediated by atorvastatin. By blocking the extracellular signal
      regulated protein kinase (ERK1/2) activation by adding U0126, we could prevent
      the apoptosis induced by atorvastatin. By Western blot we could not detect any
      change in the activation of c-jun N-terminal kinase (JNK). CONCLUSIONS:
      Atorvastatin induces apoptosis in activated HSCs acting through an ERK-dependent
      cleavage of Bid and a highly increased protease activity of caspase-9 and -3. JNK
      is not involved in atorvastatin-mediated apoptosis in HSCs.

PMID- 18339081
TI  - Zinc modulates lithium-induced hepatotoxicity in rats.
AB  - AIM: The present study explored the hepatoprotective role of zinc in lithium
      induced hepatotoxicity. METHODS: Rats received either lithium treatment in diet
      at a dose level of 1.1 g/kg diet, zinc alone at a dose level of 227 mg/L in
      drinking water, and combined lithium plus zinc or drinking water alone for
      different time durations of 1, 2 and 4 months. This study explored the hepatic
      marker enzymes, antioxidant status and histopathological investigations in the
      liver of rats following different treatments. RESULTS: The activities of glutamic
      oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase
      were found to be elevated significantly following 2 and 4 months of lithium
      treatment. Lithium-treated rats showed a significant increase in the levels of
      lipid peroxidation and superoxide dismutase and a significant inhibition in the
      levels of reduced glutathione, catalase and glutathione-S-transferase, following
      2 and 4 months of treatment. However, zinc co-administration revealed significant
      improvement in the altered activities of hepatic marker and antioxidant enzymes
      in comparison with lithium-treated animals. Lithium-treated rats also indicated
      drastic alterations in hepatic histoarchitecture and zinc co-administration
      resulted in improvement in the structure of hepatocytes. CONCLUSION: The present
      study suggests the protective potential of zinc in lithium-induced
      hepatotoxicity.

PMID- 18339082
TI  - Large-conductance calcium-activated potassium channels modulate vascular tone in
      experimental cirrhosis.
AB  - BACKGROUND: Large-conductance calcium-activated potassium (BK(Ca)) channels
      regulate vascular tone in different vascular systems. Moreover, activated hepatic
      stellate cells (HSC) contain BK(Ca) channels. The aim of this study was to
      evaluate the role of BK(Ca) channels in the regulation of vascular tone in
      control (CT) and carbon tetrachloride-cirrhotic (CH) rat livers. METHODS: Changes
      in intrahepatic vascular resistance were assessed by evaluating the portal
      perfusion pressure (PP) response to methoxamine (Mtx) in the presence of
      Iberiotoxin (Ibtx; a BK(Ca) channel blocker), NS1619 (a BK(Ca) channel opener),
      Ibtx plus the nitric oxide (NO) synthase inhibitor, N(G)-nitro-L-arginine (L-NNA)
      or L-NNA alone. In addition, in CH livers, PP dose-response curves to the NO
      donor, S-nitroso-N-acetyl-D,L-penicillamine (SNAP), were performed after pre
      incubation with Ibtx or its vehicle. BK(Ca) mRNA expression was assessed in liver
      homogenates, and BK(Ca) protein expression in HSC isolated from CT and CH livers.
      RESULTS: In CH livers, Ibtx significantly increased baseline PP and exacerbated
      the PP response to Mtx. Conversely, NS1619 induced a mild nonsignificant decrease
      of baseline PP and attenuated the hyperresponse to Mtx. CH livers exhibited an
      upregulation of both mRNA and protein of the alpha-subunit of BK(Ca). CONCLUSION:
      Large-conductance calcium-activated potassium channels are overexpressed in CH
      livers and might represent a compensatory mechanism modulating the increased
      hepatic vascular tone of cirrhosis.

PMID- 18339083
TI  - Hepatocellular carcinoma as a coincidental finding in a patient undergoing
      surgery for focal nodular hyperplasia.

PMID- 18339084
TI  - Budd-Chiari syndrome in sarcoidosis involving liver.

PMID- 18339086
TI  - Breed-related disorders of cats.

PMID- 18339087
TI  - Meticillin-resistant Staphylococcus aureus in a veterinary orthopaedic referral
      hospital: staff nasal colonisation and incidence of clinical cases.
AB  - OBJECTIVES: To evaluate staff nasal colonisation with meticillin-resistant
      Staphylococcus aureus in a veterinary orthopaedic referral hospital, and its
      effect on the occurrence of meticillin-resistant Staphylococcus aureus-associated
      postoperative wound complications in orthopaedic and spinal surgical patients.
      METHODS: Nasal bacterial swabs were collected from veterinary staff and
      environmental surfaces swabbed at six monthly intervals for meticillin-resistant
      Staphylococcus aureus monitoring over an 18 month period. The incidence of
      meticillin-resistant Staphylococcus aureus-associated postoperative wound
      complications of two veterinary orthopaedic surgeons was reviewed for a period
      when one was positive for nasal meticillin-resistant Staphylococcus aureus.
      RESULTS: Meticillin-resistant Staphylococcus aureus was isolated from a maximum
      of two out of 10 staff on each occasion. The persistently infected clinician was
      primary surgeon in 180 cases, of which four developed meticillin-resistant
      Staphylococcus aureus-associated wound complications. None of 141 operations led
      by the other surgeon developed meticillin-resistant Staphylococcus aureus
      associated complications. This difference is not statistically significant
      (P=0.0974). The 95 per cent confidence interval for this odds ratio was 0.83 to
      44.0. Meticillin-resistant Staphylococcus aureus resistance patterns of the human
      nasal isolates and three of four wound-associated isolates were similar. CLINICAL
      SIGNIFICANCE: Veterinary workers are at increased risk for meticillin-resistant
      Staphylococcus aureus colonisation, so it is likely that many veterinary patients
      are treated by meticillin-resistant Staphylococcus aureus-positive staff. Nasal
      colonisation of veterinary surgeons with meticillin-resistant Staphylococcus
      aureus appears to present only a small risk to their patients when appropriate
      infection control procedures are followed.

PMID- 18339088
TI  - Clinical and neurological characteristics of aortic thromboembolism in dogs.
AB  - OBJECTIVES: To characterise the clinical presentation and neurological
      abnormalities in dogs affected by aortic thromboembolism. METHODS: The medical
      records of 13 dogs diagnosed with aortic thromboembolism as the cause of the
      clinical signs, and where a complete neurological examination was performed, were
      reviewed retrospectively. RESULTS: The onset was acute in only four dogs, chronic
      in five dogs (with all of these presenting as exercise intolerance) or chronic
      with acute deterioration in four dogs. Dogs with an acute onset of clinical signs
      were more severely affected exhibiting neurological deficits, while dogs with a
      chronic onset of disease predominantly presented with the exercise intolerance
      and minimal deficits. The locomotor deficits included exercise intolerance with
      pelvic limb weakness (five of 13), pelvic limb ataxia (one of 13), monoparesis
      (two of 13), paraparesis (two of 13), non-ambulatory paraparesis (two of 13) and
      paraplegia (one of 13). There was an apparent male predisposition and the
      cavalier King charles spaniel was overrepresented. CLINICAL SIGNIFICANCE: The
      rate of onset of clinical signs appears to segregate dogs affected by aortic
      thromboembolism into two groups, with different clinical characteristics and
      outcomes. Dogs with an acute onset of the clinical signs tend to be more severely
      affected, while dogs with a chronic onset predominantly present with exercise
      intolerance. It is therefore important to consider aortic thromboembolism as a
      differential diagnosis in dogs with an acute onset of pelvic limb neurological
      deficits and in dogs with longer standing exercise intolerance.

PMID- 18339089
TI  - Incomplete dominant osteochondrodysplasia in heterozygous Scottish Fold cats.
AB  - This report describes an autosomal incomplete dominant pattern of inheritance for
      osteochondrodysplasia in the Scottish Fold cats. A three-generation pedigree was
      analysed. Cats with folded ears were mated with cats with normal ears. All cats
      with folded ears, which were presumably heterozygous for the mutated allele,
      developed osteochondrodysplasia in distal fore- and hindlimbs but not in other
      bones, including the tail in which bone deformity had been demonstrated in
      previous studies. The severity of the skeletal lesions of osteochondrodysplasia
      was different in each affected cat. Most of the cats with severe
      osteochondrodysplasia showed some clinical signs, but cats with mild disease were
      clinically unaffected. All Scottish Fold-related cats with folded-ear phenotype,
      even if heterozygotes, suffered from some degree of osteochondrodysplasia of the
      distal limbs.

PMID- 18339090
TI  - Hydroxycarbamide (hydroxyurea) toxicity in dogs.

PMID- 18339091
TI  - Body mass index in adults with intellectual disability: distribution,
      associations and service implications: a population-based prevalence study.
AB  - BACKGROUND: Previous studies of weight problems in adults with intellectual
      disability (ID) have generally been small or selective and given conflicting
      results. The objectives of our large-scale study were to identify inequalities in
      weight problems between adults with ID and the general adult population, and to
      investigate factors associated with obesity and underweight within the ID
      population. METHODS: We undertook a population-based prevalence study of 1119
      adults with ID aged 20 and over on the Leicestershire Learning Disability
      Register who participated in a programme of universal health checks and home
      interviews with their carers. We performed a cross-sectional analysis of the
      register data and compared the observed and expected prevalences of body mass
      index categories in the ID and general populations using indirect standardisation
      for age. We used logistic regression to evaluate the association of a range of
      probable demographic, physical, mental and skills attributes with obesity and
      underweight. RESULTS: In those aged 25 and over, the standardised morbidity ratio
      (SMR) for obesity was 0.80 (95% CI 0.64-1.00) in men and 1.48 (95% CI 1.23-1.77)
      in women. The SMR for underweight was 8.44 (95% CI 6.52-10.82) in men and 2.35
      (95% CI 1.72-3.19) in women. Among those aged 20 and over, crude prevalences were
      20.7% for obesity, 28.0% for overweight, 32.7% for normal weight and 18.6% for
      underweight. Obesity was associated with living independently/with family,
      ability to feed/drink unaided, being female, hypertension, Down syndrome and the
      absence of cerebral palsy. Underweight was associated with younger age, absence
      of Down syndrome and not taking medication. CONCLUSION: Obesity in women and
      underweight in both men and women was more common in adults with ID than in the
      general population after controlling for differences in the age distributions
      between the two populations. The associated factors suggest opportunities for
      targeting high-risk groups within the ID population for lifestyle and behaviour
      modification.

PMID- 18339092
TI  - Psychometric properties of the Mental Retardation Attitude Inventory-Revised in
      Chinese college students.
AB  - BACKGROUND: This study examines the psychometric properties of the Mental
      Retardation Attitude Inventory-Revised (MRAI-R; Antonak & Harth) in Chinese
      college students. The research questions included: (1) Is the MRAI-R a reliable
      measure for Chinese college student? (2) Is the MRAI-R related to familiarity
      with people with intellectual disabilities (PWID) and professional training? and
      (3) Does the four-factor model of the MRAI-R fit the Chinese college student
      data? METHOD: Five hundred and thirty-four college students from China
      participated in the study. Descriptive, Pearson product-moment correlation,
      Cronbach alpha reliability coefficient and factor analyses were used to examine
      the reliability and validity of the MRAI-R in this Chinese college student
      sample. RESULTS: The alpha coefficient reliability of the total scale of the MRAI
      R was 0.78. The alpha coefficient reliabilities for the integration-segregation
      (INSE) subscale, the social distance (SDIS) subscale, the private rights (PRRT)
      subscale and the subtle derogatory beliefs (SUDB) subscale were 0.50 (INSE), 0.78
      (SDIS), 0.50 (PRRT) and 0.21 (SUDB) respectively. Correlation analyses indicated
      that familiarity with PWID and professional training had a weak correlation with
      attitudes towards PWID. A confirmatory factor analysis revealed that the
      standardized factor loadings and goodness-of-fit indices were inadequate (the chi
      square/degrees of freedom ratio = 3.24; the goodness-of-fit index = 0.85; the
      comparative fit index = 0.69; the RMSEA* = 0.07). A principal axis factoring
      analysis (PAF) with oblique rotation identified three factors with 25% of the
      variance accounted for the sample. However, the results of this PAF were
      factorial complex and not interpretable in that many items of the scale had
      double loadings on more than one factor. CONCLUSIONS: The factor structure of the
      MRAI-R in this sample of Chinese college students did not replicate the structure
      found in American adults. Although the SDIS subscale of the MRAI-R appeared to be
      a reliable instrument among the four subscales of the MRAI-R, the reliabilities
      of the INSE, PRRT and SUDB subscales were low. Continuing investigations of the
      utility of the MRAI-R in Chinese culture is needed. Attitude instruments based on
      Chinese culture may be developed.

PMID- 18339093
TI  - Teaching picture-to-object relations in picture-based requesting by children with
      autism: a comparison between error prevention and error correction teaching
      procedures.
AB  - BACKGROUND: Children who have a combination of language and developmental
      disabilities with autism often experience major difficulties in learning
      relations between objects and their graphic representations. Therefore, they
      would benefit from teaching procedures that minimize their difficulties in
      acquiring these relations. This study compared two teaching procedures, an error
      prevention procedure and an error correction procedure, for teaching relations
      between objects and pictures. METHOD: Participants were two groups of children
      with autism, aged between 3 and 7 years. In the context of picture-to-object
      requesting, one group was taught using an error correction method and the other
      group with an error prevention method. The measures for each child were accuracy
      of correspondences between taught picture and object pairs and accuracy of
      delayed correspondences in learning outcome tests with all combinations of object
      and picture pairs presented to them throughout the study. RESULTS: The group
      receiving the error prevention-based teaching made significantly fewer errors
      during the teaching phases and in their learning outcome test for correspondences
      between all combinations of pictures and objects. CONCLUSIONS: The error
      prevention teaching procedure would seem to provide a more efficient and
      ecologically valid method than the error correction procedure for teaching
      relations between objects and their graphic-based referents. Improvements in the
      methodology were suggested for providing a stronger basis for comparison between
      error correction and error prevention teaching methods.

PMID- 18339094
TI  - Clarification of the memory artefact in the assessment of suggestibility.
AB  - AIM: The Gudjonsson Suggestibility Scale (GSS) assesses suggestibility by asking
      respondents to recall a short story, followed by exposure to leading questions
      and pressure to change their responses. Suggestibility, as assessed by the GSS,
      appears to be elevated in people with intellectual disabilities (ID). This has
      been shown to reflect to some extent the fact that people with ID have poor
      recall of the story; however, there are discrepancies in this relationship. The
      aim of the present study was to investigate whether a closer match between memory
      and suggestibility would be found using a measure of recognition memory rather
      than free recall. METHOD: Three modifications to the procedure were presented to
      users of a learning disabilities day service. In all three experiments, a measure
      of forced-choice recognition memory was built into the suggestibility test. In
      experiments 1 and 2, the GSS was presented using either divided presentation
      (splitting the story into two halves, with memory and suggestibility tests after
      each half) or multiple presentation (the story was presented three times before
      presentation of the memory and suggestibility tests). Participants were tested
      twice, once with the standard version of the test and once with one of the
      modified versions. In experiment 3, an alternative suggestibility scale (ASS3)
      was created, based on real events in a learning disabilities day service. The
      ASS3 was presented to one group of participants who had been present at the
      events, and a second group who attended a different day service, to whom the
      events were unfamiliar. RESULTS: As observed previously, suggestibility was not
      closely related to free recall performance: recall was increased equally by all
      three manipulations, but they produced, respectively, no effect, a modest effect
      and a large effect on suggestibility. However, the effects on suggestibility were
      closely related to performance on the forced-choice recognition memory task:
      divided presentation of the GSS2 had no effect on either of these measures;
      multiple presentation of the GSS2 produced a modest increase in recognition
      memory and a modest decrease in suggestibility; and replacing the GSS with the
      ASS3 produced a large increase in recognition memory and a large decrease in
      suggestibility. IMPLICATIONS: The results support earlier findings that the GSS
      is likely to overestimate how suggestible a person will be in relation to a
      personally significant event. This reflects poor recognition memory for the
      material being tested, rather than increased suggestibility per se. People with
      ID may in fact be relatively non-suggestible for well-remembered events, which
      would include personally significant events, particularly those witnessed
      recently.

PMID- 18339095
TI  - Three persons with multiple disabilities accessing environmental stimuli and
      asking for social contact through microswitch and VOCA technology.
AB  - BACKGROUND: Direct access to environmental stimuli and opportunity to ask for
      social contact/attention may be considered highly relevant objectives for persons
      with multiple disabilities. We assessed the possibility of enabling three of
      these persons (two children and one adolescent) to combine two microswitches (for
      accessing environmental stimuli) and a Voice Output Communication Aid (VOCA),
      which allowed them to ask for caregiver's attention. METHODS: Initially, the
      participants were required to use each of the two microswitches individually and
      then together. Thereafter, they were taught to use the VOCA. Eventually, the VOCA
      was available together with the microswitches, and the participants could use any
      of the three. RESULTS: The results, which support preliminary data on this topic,
      showed that all participants (1) were able to operate the two microswitches as
      well as the VOCA; and (2) used all three of them consistently when they were
      simultaneously available. CONCLUSIONS: Teaching persons with multiple
      disabilities to combine a VOCA with conventional microswitches may enrich their
      general input, emphasize their active social role and eventually enhance their
      social image.

PMID- 18339097
TI  - In vivo relevance for platelet glycoprotein Ibalpha residue Tyr276 in thrombus
      formation.
AB  - BACKGROUND: Platelet glycoprotein (GP) Ib-IX-V supports platelet adhesion on
      damaged vascular walls by binding to von Willebrand factor (VWF). For several
      decades it has been recognized that the alpha-subunit of GP (GPIbalpha) also
      binds thrombin but the physiological relevance, if any, of this interaction was
      unknown. Previous studies have shown that a sulfated tyrosine 276 (Tyr276) is
      essential for thrombin binding to GPIbalpha. OBJECTIVES: This study investigated
      the in vivo relevance of GPIbalpha residue Tyr276 in hemostasis and thrombosis.
      METHODS: Transgenic mouse colonies expressing the normal human GPIbalpha subunit
      or a mutant human GPIbalpha containing a Phe substitution for Tyr276 (hTg(Y276F))
      were generated. Both colonies were bred to mice devoid of murine GPIbalpha.
      RESULTS: Surface-expressed GPIbalpha levels and platelet counts were similar in
      both colonies. hTg(Y276F) platelets were significantly impaired in binding alpha
      thrombin but displayed normal binding to type I fibrillar collagen and human VWF
      in the presence of ristocetin. In vivo thrombus formation as a result of chemical
      damage (FeCl(3)) demonstrated that hTg(Y276F) mice have a delayed time to
      occlusion followed by unstable blood flow indicative of embolization. In models
      of laser-induced injury, thrombi developing in hTg(Y276F) animals were also less
      stable. CONCLUSIONS: The results demonstrate that GPIbalpha residue Tyr276 is
      physiologically important, supporting stable thrombus formation in vivo.

PMID- 18339098
TI  - Methamphetamine precursor regulation: are we controlling or diverting the drug
      problem?

PMID- 18339099
TI  - National drug abuse situation in Vietnam--how accurate are the projections?

PMID- 18339100
TI  - Sexual orientation and adolescent substance use: a meta-analysis and
      methodological review.
AB  - AIMS: Several decades of research have shown that lesbian, gay and bisexual (LGB)
      adults are at high risk for substance use and substance use disorders (SUDs).
      These problems may often start prior to young adulthood; however, relatively
      little is known about risk for substance use in LGB adolescents. The primary aims
      of this paper were to conduct a meta-analysis of the relationship between sexual
      orientation and adolescent substance use and a systematic review and critique of
      the methodological characteristics of this literature. METHODS: Medical and
      social science journals were searched using Medline and PsychInfo. Studies were
      included if they tested the relationship between sexual orientation and
      adolescent substance use. Eighteen published studies were identified. Data
      analysis procedures followed expert guidelines, and used National Institutes of
      Health (NIH)-sponsored meta-analysis software. RESULTS: LGB adolescents reported
      higher rates of substance use compared to heterosexual youth (overall odds ratio
      = 2.89, Cohen's d = 0.59). Effect sizes varied by gender, bisexuality status,
      sexual orientation definition and recruitment source. None of the studies tested
      mediation and only one tested moderation. One employed a matched comparison group
      design, one used a longitudinal design, and very few controlled for possible
      confounding variables. CONCLUSIONS: The odds of substance use for LGB youth were,
      on average, 190% higher than for heterosexual youth and substantially higher
      within some subpopulations of LGB youth (340% higher for bisexual youth, 400%
      higher for females). Causal mechanisms, protective factors and alternative
      explanations for this effect, as well as long-term substance use outcomes in LGB
      youth, remain largely unknown.

PMID- 18339101
TI  - Nicotine patch therapy prior to quitting smoking: a meta-analysis.
AB  - AIM: To evaluate the incremental efficacy of starting nicotine patch treatment
      prior to quitting compared to the current regimen of starting patch treatment on
      the target quit day. DESIGN AND MEASUREMENTS: Meta-analysis of four eligible
      studies using pre-cessation patch treatment, located by database search and
      contacts with cessation researchers. The studies all compared starting treatment
      with nicotine patch prior to the target quit date to starting active treatment at
      the quit date, some in the context of concurrent mecamylamine treatment. The
      primary end-point for the analysis was continuous abstinence for at least 28 days
      assessed at 6 weeks following quit day; 6-month outcomes were also examined.
      FINDINGS: Compared to starting active patch treatment on quit day, pre-cessation
      treatment with nicotine patches was found to double the odds of quitting. This
      was true both at 6 weeks [pooled odds ratio (OR) = 1.96, 95% confidence interval
      (CI): 1.31-2.93] and 6 months (pooled OR = 2.17, 95% CI: 1.46-3.22) treatment
      outcomes. Mecamylamine co-treatment did not modify these effects. CONCLUSIONS:
      Across the four studies analyzed, pre-cessation patch treatment was found to
      produce a robust increase in quit rates compared to current regimens starting
      patch at quit day. Pre-cessation patch use represents a promising innovation in
      smoking cessation therapy with potential beneficial implications for improved
      public health by further increasing quitting success.

PMID- 18339102
TI  - Breaking away from a narrow prescribing protocol for medicinal nicotine.

PMID- 18339103
TI  - Self-help smoking cessation interventions in pregnancy: a systematic review and
      meta-analysis.
AB  - AIMS: Self-help smoking cessation interventions for pregnant smokers are of
      importance due to their potential to be wide-reaching, low-cost and their appeal
      to pregnant smokers who are interested in quitting smoking. To date, however,
      there has been no systematic assessment of their efficacy. This systematic review
      aimed to assess the efficacy of self-help interventions for pregnant smokers and
      to investigate whether self-help material intensity, type or delivery are
      associated with cessation. METHODS: The literature was searched for randomized
      and quasi-randomized controlled trials of self-help smoking cessation
      interventions for pregnant smokers without significant cessation counselling.
      Fifteen trials met the inclusion criteria and relevant data were extracted
      independently. RESULTS: The primary meta-analysis pooled 12 trials comparing
      usual care (median quit rate 4.9%) with self-help (median quit rate 13.2%) and
      yielded a pooled odds ratio (OR) of 1.83 [95% confidence interval (CI) 1.23
      2.73], indicating that self-help interventions on average nearly double the odds
      of quitting compared with standard care. However, a further meta-analysis failed
      to find evidence that intervention materials of greater intensity increase
      quitting significantly over materials of lesser intensity (pooled OR = 1.25, 95%
      CI 0.81-1.94). There was insufficient evidence to determine whether the tailoring
      of materials or levels of one-to-one contact were related to intervention
      efficacy. CONCLUSIONS: Self-help interventions appear to be more effective than
      standard care although, due mainly to a lack of trials, it is unclear whether
      more sophisticated and intensive approaches increase intervention effectiveness.

PMID- 18339104
TI  - The case for the plain packaging of tobacco products.
AB  - AIMS: The Framework Convention on Tobacco Control (FCTC) requires nations that
      have ratified the convention to ban all tobacco advertising and promotion. In the
      face of these restrictions, tobacco packaging has become the key promotional
      vehicle for the tobacco industry to interest smokers and potential smokers in
      tobacco products. This paper reviews available research into the probable impact
      of mandatory plain packaging and internal tobacco industry statements about the
      importance of packs as promotional vehicles. It critiques legal objections raised
      by the industry about plain packaging violating laws and international trade
      agreements. METHODS: Searches for available evidence were conducted within the
      internal tobacco industry documents through the online document archives; tobacco
      industry trade publications; research literature through the Medline and Business
      Source Premier databases; and grey literature including government documents,
      research reports and non-governmental organization papers via the Google internet
      search engine. RESULTS: Plain packaging of all tobacco products would remove a
      key remaining means for the industry to promote its products to billions of the
      world's smokers and future smokers. Governments have required large surface areas
      of tobacco packs to be used exclusively for health warnings without legal
      impediment or need to compensate tobacco companies. CONCLUSIONS: Requiring plain
      packaging is consistent with the intention to ban all tobacco promotions. There
      is no impediment in the FCTC to interpreting tobacco advertising and promotion to
      include tobacco packs.

PMID- 18339105
TI  - Modern-day miracles: declining per capita consumption and increased awareness of
      alcohol's damage in a drinking-oriented society.

PMID- 18339106
TI  - Alcohol outlet density and assault: a spatial analysis.
AB  - AIMS: A large number of studies have found links between alcohol outlet densities
      and assault rates in local areas. This study tests a variety of specifications of
      this link, focusing in particular on the possibility of a non-linear
      relationship. DESIGN: Cross-sectional data on police-recorded assaults during
      high alcohol hours, liquor outlets and socio-demographic characteristics were
      obtained for 223 postcodes in Melbourne, Australia. These data were used to
      construct a series of models testing the nature of the relationship between
      alcohol outlet density and assault, while controlling for socio-demographic
      factors and spatial auto-correlation. Four types of relationship were examined: a
      normal linear relationship between outlet density and assault, a non-linear
      relationship with potential threshold or saturation densities, a relationship
      mediated by the socio-economic status of the neighbourhood and a relationship
      which takes into account the effect of outlets in surrounding neighbourhoods.
      FINDINGS: The model positing non-linear relationships between outlet density and
      assaults was found to fit the data most effectively. An increasing accelerating
      effect for the density of hotel (pub) licences was found, suggesting a plausible
      upper limit for these licences in Melbourne postcodes. CONCLUSIONS: The study
      finds positive relationships between outlet density and assault rates and
      provides evidence that this relationship is non-linear and thus has critical
      values at which licensing policy-makers can impose density limits.

PMID- 18339107
TI  - How much can you drink before driving? The influence of riding with impaired
      adults and peers on the driving behaviors of urban and rural youth.
AB  - AIMS: Following an ecological model to specify risks for impaired driving, we
      assessed the effects of youth attitudes about substance use and their experiences
      of riding in cars with adults and peers who drove after drinking alcohol or
      smoking cannabis on the youths' own driving after drinking or using cannabis.
      DESIGN AND METHODS: Participants were 2594 students in grades 10 and 12 (mean age
      = 16 years and 2 months; 50% girls) from public high schools in urban (994) and
      rural communities (1600) on Vancouver Island in British Columbia, Canada; 1192 of
      these were new drivers with restricted licenses. Self-report data were collected
      in anonymous questionnaires. Regression analyses were used to assess the
      independent and interacting effects of youth attitudes about substance use and
      their experiences of riding in cars with adults or peers who drove after drinking
      alcohol or smoking cannabis on youth driving. FINDINGS: Youth driving risk
      behaviors were associated independently with their own high-risk attitudes and
      experiences riding with peers who drink alcohol or use cannabis and drive.
      However, risks were highest for the youth who also report more frequent
      experiences of riding with adults who drink alcohol or use cannabis and drive.
      CONCLUSIONS: Prevention efforts should be expanded to include the adults and
      peers who are role models for new drivers and to increase youths' awareness of
      their own responsibilities for their personal safety as passengers.

PMID- 18339108
TI  - Coping skills training and contingency management treatments for marijuana
      dependence: exploring mechanisms of behavior change.
AB  - AIMS: Achieving abstinence in the treatment of marijuana dependence has been
      difficult. To date the most successful treatments have included combinations of
      motivation enhancement treatment (MET) plus cognitive-behavioral coping skills
      training (CBT) and/or contingency management (ContM) approaches. Although these
      treatment approaches are theoretically based, their mechanisms of action have not
      been explored fully. The purpose of the present study was to explore mechanisms
      of behavior change from a marijuana treatment trial in which CBT and ContM were
      evaluated separately and in combination. DESIGN: A dismantling design was used in
      the context of a randomized clinical trial. SETTING: The setting was an out
      patient treatment research facility located in a university medical center.
      PARTICIPANTS: Participants were 240 adult marijuana smokers, meeting criteria for
      cannabis dependence. INTERVENTIONS: Participants were assigned to one of four 9
      week treatment conditions: a case management control condition, MET/CBT coping
      skills training, ContM and MET/CBT + ContM. MEASUREMENTS: Outcome measures were
      total 90-day abstinence, recorded every 90 days for 12 months post-treatment.
      FINDINGS: Regardless of treatment condition, abstinence in near-term follow-ups
      was predicted most clearly by abstinence during treatment, but long-term
      abstinence was predicted by use of coping skills and especially by post-treatment
      self-efficacy for abstinence. CONCLUSIONS: It was concluded that the most
      efficacious treatments for marijuana dependence are likely to be those that
      increase self-efficacy.

PMID- 18339109
TI  - Why and how do substance abuse treatments work? Investigating mediated change.

PMID- 18339110
TI  - The shifting pattern of cause-specific mortality in a cohort of human
      immunodeficiency virus-infected and non-infected injecting drug users.
AB  - AIMS: To monitor changes in cause-specific mortality before and after 1997
      according to human immunodeficiency virus (HIV) serological status in a cohort of
      injecting drug users (IDUs) observed for a 17-year period (1987--2004). DESIGN:
      Community-based prospective cohort study of IDUs recruited in three acquired
      immunodeficiency virus (AIDS) prevention centres (1987--96) and followed-up until
      to 2004. METHODS: We obtained annual overall mortality rates and mortality rates
      by specific causes according to HIV status. Poisson regression models were
      adjusted to compare mortality rates between calendar periods. Significant changes
      in slope trends were evaluated by join-point regression. Disease-specific
      mortality rates were estimated using competing risk models. FINDINGS: From 7186
      IDUs recruited (80677.218 person-years), 1589 deaths were observed with an
      overall mortality rate of 19.7 per 1000 person-years (95% CI, 18.8-20.7). This
      rate decreased from 22.9 per 1000 (95% CI, 21.4-24.7) before 1997 to 17.4 per
      1000 (95% CI, 16.3-18.6) after 1997 [relative risk (RR) 0.83; 95% confidence
      interval (CI), 0.75-0.92]. Risk of death for HIV-positive was four times higher
      than for HIV-negative (RR 4.08; 95% CI, 3.63-4.58). Among HIV-positive
      individuals a significantly decreased change point in trend was found in 1997 for
      both total and AIDS mortality. HIV-negative individuals showed a similar pattern
      for drug overdose, suicide and accident mortality. Both groups showed an increase
      in proportional mortality by liver-related causes, cardiovascular diseases and
      cancer. Furthermore, a progressively increasing trend was observed for the three
      causes. However, there were no significant differences according to serological
      groups. CONCLUSIONS: Cardiovascular and cancer mortality are increasing among
      IDUs, but the increases are not related to HIV infection. We have not found a
      link between highly active antiretroviral therapy (HAART) introduction and
      increases in mortality for specific causes.

PMID- 18339111
TI  - Antiretroviral therapy: a key part of the public health response to injection
      drug use.

PMID- 18339112
TI  - Long-term effectiveness of computer-generated tailored patient education on
      benzodiazepines: a randomized controlled trial.
AB  - AIMS: Chronic benzodiazepine use is highly prevalent and is associated with a
      variety of negative health consequences. The present study examined the long-term
      effectiveness of a tailored patient education intervention on benzodiazepine use.
      DESIGN: A randomized controlled trial was conducted comprising three arms,
      comparing (i) a single tailored intervention; (ii) a multiple tailored
      intervention and (iii) a general practitioner letter. The post-test took place
      after 12 months. PARTICIPANTS: Five hundred and eight patients using
      benzodiazepines were recruited by their general practitioners and assigned
      randomly to one of the three groups. INTERVENTION: Two tailored interventions,
      the single tailored intervention (patients received one tailored letter) and the
      multiple tailored intervention (patients received three sequential tailored
      letters at intervals of 1 month), were compared to a short general practitioner
      letter that modelled usual care. The tailored interventions not only provided
      different and more information than the general practitioner letter; they were
      also personalized and adapted to individual baseline characteristics. The
      information in both tailored interventions was the same, but in the multiple
      tailored intervention the information was provided to the participants spread
      over three occasions. In the multiple tailored intervention, the second and the
      third tailored letters were based on short and standardized telephone interviews.
      MEASUREMENTS: Benzodiazepine cessation at post-test was the outcome measure.
      FINDINGS: The results showed that participants receiving the tailored
      interventions were twice as likely to have quit benzodiazepine use compared to
      the general practitioner letter. Particularly among participants with the
      intention to discontinue usage at baseline, both tailored interventions led to
      high percentages of those who actually discontinued usage (single tailored
      intervention 51.7%; multiple tailored intervention 35.6%; general practitioner
      letter 14.5%). CONCLUSIONS: It was concluded that tailored patient education can
      be an effective tool for reducing benzodiazepine use, and can be implemented
      easily.

PMID- 18339113
TI  - Predictors of 4-year outcome of community residential treatment for patients with
      substance use disorders.
AB  - AIMS: This study examined systematically how predictors of substance use disorder
      (SUD) treatment outcome worked together over time and identified mediators and
      moderators of outcome. DESIGN: The MacArthur model was applied in this
      naturalistic study to identify how baseline, discharge and 1-year follow-up
      factors worked together to predict 4-year improvement in substance-related
      problems. SETTING: Eighty-eight community residential facilities were selected
      based on geographic representativeness, number of patient referrals and type of
      treatment orientation. PARTICIPANTS: Of 2796 male patients who completed intake
      assessments, 2324 were assessed at the 1-year follow-up and 2023 at the 4-year
      follow-up. MEASUREMENTS: Self-report measures of symptom severity, functioning,
      social resources and coping, treatment and involvement in Alcoholics Anonymous
      (AA) were collected at baseline and at 1- and 4-year follow-ups. Provider-rated
      treatment participation measures were obtained at discharge. FINDINGS: Greater
      substance use severity, more psychiatric symptoms, more prior arrests and
      stronger belief in AA-related philosophy at treatment entry predicted improvement
      significantly in substance-related problems 4 years later. At the 1-year follow
      up, being employed and greater use of AA-related coping predicted outcome
      significantly. AA-related coping at 1 year mediated the relationship partially
      between belief in AA philosophy at treatment entry and 4-year outcome.
      CONCLUSIONS: The findings highlight the unique and positive impact of AA
      involvement on long-term SUD treatment outcome and extend understanding of why AA
      is beneficial for patients.

PMID- 18339114
TI  - Markers for hepatitis A, B and C in methadone maintained patients: an
      unexpectedly high co-infection with silent hepatitis B.
AB  - AIMS: To determine the prevalence of hepatitis A, B and C viruses in patients
      attending a methadone maintenance clinic in New York City. DESIGN: Cross
      sectional. SETTING: The Adult Services Clinic of Weill Cornell Medical College,
      an urban hospital-affiliated methadone program. PARTICIPANTS: Former heroin
      addicted adults (n = 103) on methadone maintenance therapy. MEASUREMENTS: Markers
      for hepatitis A virus [HAV immunoglobulin M (IgM) and imunoglobulin G (IgG)],
      hepatitis B [hepatitis B surface antigen (HBsAg), hepatitis B surface antibody
      (HBsAb) and hepatitis B core antibody (HBcAb)] and hepatitis C virus (HCVAb).
      Serum alanine aminotransferase (ALT) and quantitative HCV RNA were also obtained.
      Qualitative detection of HBV DNA and HCV genotype were obtained in a subset of
      subjects. FINDINGS: More than 40% of subjects had markers for all three viruses.
      HCVAb was the most prevalent (83.5%), followed by HBcAb (65.0%), HAV IgG (46.1%)
      and HBsAb (41.1%). Hepatitis C RNA was detected in 70.6% of HCVAb positive
      subjects. While no subject had HBsAg, HBV DNA was detected in 26.4% of subjects
      who underwent this measure; all (n = 20) had HBcAb as their only HBV marker. The
      presence of HBV DNA did not influence ALT. Subjects with HCV RNA had higher ALTs
      than those without HCV RNA. CONCLUSIONS: Most methadone-maintained subjects had
      at least one marker for viral hepatitis, with 41.8% having markers for HAV, HBV
      and HCV. A quarter of subjects had silent HBV infection, defined as the presence
      of HBV DNA in the absence of HBsAg. These subjects should be considered
      infectious and pose a public health risk.

PMID- 18339115
TI  - Preliminary evidence for gender-specific effects of topiramate as a potential aid
      to smoking cessation.
AB  - AIMS: Study aims were threefold: (i) to determine the feasibility, potential
      efficacy and safety of topiramate as an aid to smoking cessation; (ii) to examine
      potential predictors of abstinence including gender; and (iii) to explore
      topiramate's effects on tobacco withdrawal and post-cessation weight gain.
      DESIGN: Randomized, double-blind, placebo-controlled, 11-week clinical trial with
      a 6-week dosage titration period and 5 weeks of maintenance treatment. SETTING:
      Single-site, out-patient, randomized clinical trial. PARTICIPANTS: Thirty-eight
      adult male and 49 female chronic smokers who smoked an average of > 10 cigarettes
      per day and who were motivated to try to quit smoking. INTERVENTION: Random
      assignment to receive either topiramate (n = 43) up to 200 mg daily in divided
      doses or placebo (n = 44) orally combined with brief counseling over an 11-week
      period. MEASUREMENTS: Carbon monoxide (CO)-confirmed 4-week prolonged abstinence
      rate during weeks 8-11. Changes in tobacco withdrawal, body weight and safety
      parameters were also assessed. FINDINGS: Overall, no significant increase in the
      prolonged abstinence rate was detected, but logistic regression analysis
      indicated significant gender-specific differences. Men treated with topiramate
      were nearly 16 times more likely to quit smoking than women on topiramate [37.5%
      versus 3.7%; odds ratio (OR) = 15.6; P = 0.016] and were roughly four times more
      likely to quit smoking than placebo-treated men (37.5% versus 13.6%; OR = 3.8; P
      = 0.098). Topiramate-treated men reported significantly lower tobacco withdrawal
      scores than both women taking topiramate and men on placebo. On average, male
      cessators on placebo gained 3.30 kg, whereas topiramate led to a 0.72 kg weight
      loss (P = 0.03). Study discontinuation rates due to adverse events (AEs) were
      significantly higher in the topiramate group (topiramate 23% versus placebo 2%).
      The most commonly reported AEs in the topiramate arm were paraesthesia, fatigue,
      difficulty with concentration/attention and nervousness. CONCLUSIONS: Topiramate
      produced gender-specific effects on smoking cessation. Male smokers had markedly
      greater quit rates than female smokers and men were roughly four times more
      likely to quit smoking when treated with topiramate as compared to placebo.
      Topiramate was fairly well tolerated, although higher discontinuation rates were
      seen. Topiramate's triple effects aiding smoking abstinence, attenuating nicotine
      withdrawal and preventing post-cessation weight gain might make it a promising
      agent for treating tobacco addiction, at least in men.

PMID- 18339116
TI  - Information retrieval and terminology.

PMID- 18339117
TI  - Keeping track of time under ice and snow in a sub-arctic lake: plasma melatonin
      rhythms in Arctic charr overwintering under natural conditions.
AB  - Although photoperiod is considered as a major environmental cue for timing of
      seasonal events in fish, little is known about the photic information perceived
      by fish in different aquatic environments. The strongly seasonal Arctic charr,
      Salvelinus alpinus, reside in lakes covered by thick ice and snow throughout the
      dark winter in the north. In the present study, we have measured diel changes in
      their plasma melatonin concentrations from September to June in Lake Storvatnet
      (70 degrees N), northern Norway. In addition, we have measured the in vitro
      melatonin production of Arctic charr pineal glands held at experimental light
      conditions. From September to April a diel profile in plasma melatonin was seen
      in the charr in Lake Storvatn, with highest concentrations at night. This profile
      reflected the prevailing above-surface photoperiod, even in February when there
      were minimal changes in sub-surface irradiance between day and night. In June,
      plasma melatonin was low throughout the 24-hr cycle, despite there being a marked
      sub-surface difference in irradiance between night and day. At this time the
      irradiance in night probably remained above the threshold for suppression of
      melatonin production. The in vitro experiments revealed no endogenous rhythm in
      the pineal melatonin secretion, supporting the conclusion that the diel profile
      seen in the Arctic charr in their natural habitat was driven by ambient
      photoperiod. In conclusion, the Arctic charr appear to keep track of time even
      under the extreme conditions of high latitudes during winter, when lakes have
      thick ice and snow cover.

PMID- 18339118
TI  - Melatonin ameliorates hippocampal nitric oxide production and large conductance
      calcium-activated potassium channel activity in chronic intermittent hypoxia.
AB  - Melatonin protects against hippocampal injury induced by intermittent hypoxia
      (IH). IH-induced oxidative stress is associated with decreases in constitutive
      production of nitric oxide (NO) and in the activity of large conductance calcium
      activated potassium (BK) channels in hippocampal neurons. We tested the
      hypothesis that administration of melatonin alleviates the NO deficit and
      impaired BK channel activity in the hippocampus of IH rats. Sprague-Dawley rats
      were injected with melatonin (10 mg/kg, i.p.) or vehicle before daily IH exposure
      for 8 hr for 7 days. The NO and intracellular calcium ([Ca2+]i) levels in the CA1
      region of hippocampal slices were measured by electrochemical microsenor and
      spectrofluorometry, respectively. The activity of BK channels was recorded by
      patch-clamping electrophysiology in dissociated CA1 neurons. Malondialdehyde
      levels were increased in the hippocampus of hypoxic rats and were lowered by the
      melatonin treatment. Levels of NO under resting and hypoxic conditions, and the
      protein expression of neuronal NO synthase (nNOS) were significantly reduced in
      the CA1 neurons of hypoxic animals compared with the normoxic controls. These
      deficits were mitigated in the melatonin-treated hypoxic rats with an improved
      [Ca2+]i response to acute hypoxia. The open probability of BK channels was
      decreased in the hypoxic rats and was partially restored in the melatonin-treated
      animals, without alterations in the expression of channel subunits and unitary
      conductance. Acute treatment of melatonin had no significant effects on the BK
      channel activity or on the [Ca2+]i response to hypoxia. Collectively, these
      results suggest that melatonin ameliorates the constitutive NO production and BK
      channel activity via an antioxidant mechanism against an IH-induced down
      regulation of nNOS expression in hippocampal neurons.

PMID- 18339119
TI  - N-nitrosomelatonin outcompetes S-nitrosocysteine in inhibiting glyceraldehyde 3
      phosphate dehydrogenase: first evidence that N-nitrosomelatonin can modify
      protein function.
AB  - Low-molecular-weight S-nitrosothiols (RSNOs) are well known for their capability
      to transnitrosate cysteine residues of enzymes thereby altering their catalytic
      activity. It is unknown, however, whether N-nitrosomelatonin (NOMela) which is
      highly effective in transnitrosating low-molecular-weight thiols (RSHs) can also
      alter protein function. In the present study, we report on such a capability with
      glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a target enzyme. Reaction of
      NOMela with GAPDH resulted in an increase of RSNOs at the expense of RSHs.
      Somewhat surprisingly, NOMela was about 10-fold more effective than S
      nitrosocysteine in inhibiting GAPDH. Vitamin C and glutathione increased the
      NOMela-dependent inhibition of the enzyme by accelerating the intermediacy of
      nitroxyl which is also highly effective in nitrosating RSHs. The occurrence of
      this intermediate during the NOMela-vitamin C reaction was verified by using
      Mn(III)-tetrakis(1-methyl-4-pyridyl)porphorin pentachloride as nitroxyl
      scavenger. The NOMela-dependent inactivation of GAPDH was so effective that this
      reaction can be used to quantify NOMela with high sensitivity.

PMID- 18339120
TI  - Protective effect of melatonin on Ca2+ homeostasis and contractility in acute
      cholecystitis.
AB  - Impaired Ca2+ homeostasis and smooth muscle contractility co-exist in acute
      cholecystitis (AC) leading to gallbladder dysfunction. There is no
      pharmacological treatment for this pathological condition. Our aim was to
      evaluate the effects of melatonin treatment on Ca2+ signaling pathways and
      contractility altered by cholecystitis. [Ca2+]i was determined by epifluorescence
      microscopy in fura-2 loaded isolated gallbladder smooth muscle cells, and
      isometric tension was recorded from gallbladder muscle strips. Malondialdehyde
      (MDA) and reduced glutathione (GSH) contents were determined by spectrophotometry
      and cycloxygenase-2 (COX-2) expression was quantified by western blot. Melatonin
      was tested in two experimental groups, one of which underwent common bile duct
      ligation for 2 days and another that was later de-ligated for 2 days.
      Inflammation-induced impairment of Ca2+ responses to cholecystokinin and caffeine
      were recovered by melatonin treatment (30 mg/kg). This treatment also ameliorated
      the detrimental effects of AC on Ca2+ influx through both L-type and capacitative
      Ca2+ channels, and it was effective in preserving the pharmacological phenotype
      of these channels. Despite its effects on Ca2+ homeostasis, melatonin did not
      improve contractility. After de-ligation, Ca2+ influx and contractility were
      still impaired, but both were recovered by melatonin. These effects of melatonin
      were associated to a reduction of MDA levels, an increase in GSH content and a
      decrease in COX-2 expression. These findings indicate that melatonin restores
      Ca2+ homeostasis during AC and resolves inflammation. In addition, this
      indoleamine helps in the subsequent recovery of functionality.

PMID- 18339121
TI  - Acute allograft rejection and immunosuppression: influence on endogenous
      melatonin secretion.
AB  - Melatonin displays a dose-dependent immunoregulatory effect in vitro and in vivo.
      Exogenous high-dose melatonin therapy exerted an immunosuppressive effect,
      abrogating acute rejection (AR), significantly prolonging transplant survival.
      Endogenous melatonin secretion, in response to heterotopic rat cardiac allograft
      transplantation (Tx), was investigated during the AR response and under
      standardized immunosuppressive maintenance therapy with cyclosporin A (CsA) and
      rapamycin (RPM). Recipients of syngeneic transplants, and recipients of
      allogeneic grafts, either untreated or receiving immunosuppressive therapy
      constituted the experimental groups. Endogenous circadian melatonin levels were
      measured at 07:00, 19:00, and 24:00 hr, using a novel radioimmunoassay (RIA)
      procedure, under standardized 12-hr-light/dark-conditions (light off: 19:00 hr;
      light on: 07:00 hr), before and after Tx. Neither the operative trauma, nor the
      challenge with a perfused allograft or the AR response influenced endogenous
      melatonin peak secretion. Immunosuppressive therapy with CsA led to a significant
      increase in peak secretion, measured for days 7 (212 +/- 40.7 pg/mL; P < 0.05),
      14 (255 +/- 13.9 pg/mL; P < 0.001), and 21 (219 +/- 34 pg/mL; P < 0.01) after Tx,
      as compared with naive animals (155 +/- 25.8 pg/mL). In contrast, treatment with
      RPM significantly decreased the melatonin peak post-Tx up to day 7 (87 +/- 25.2
      pg/mL; P < 0.001), compared with naive animals (155 +/- 25.8 pg/mL). These
      findings imply a robust nature of the endogenous circadian melatonin secretion
      kinetics, even against the background of profound allogeneic stimuli.
      Immunosuppressive maintenance therapy with CsA and RPM modulated early melatonin
      secretion, indicating a specific secondary action of these drugs. Further studies
      are necessary to disclose the long-term effect of immunosuppressive therapy on
      circadian melatonin secretion in transplant recipients.

PMID- 18339122
TI  - Effects of mobile phone electromagnetic fields at nonthermal SAR values on
      melatonin and body weight of Djungarian hamsters (Phodopus sungorus).
AB  - In three experiments, adult male Djungarian hamsters (Phodopus sungorus) were
      exposed 24 hr/day for 60 days to radio frequency electromagnetic fields (RF-EMF)
      at 383, 900, and 1800 MHz, modulated according to the TETRA (383 MHz) and GSM
      standards (900 and 1800 MHz), respectively. A radial waveguide system ensured a
      well defined and uniform exposure at whole-body averaged specific absorption
      rates of 80 mW/kg, which is equal to the upper limit of whole-body exposure of
      the general population in Germany and other countries. For each experiment, using
      two identical waveguides, hamsters were exposed (n = 120) and sham-exposed (n =
      120) in a blind fashion. In all experiments, pineal and serum melatonin levels as
      well as the weights of testes, brain, kidneys, and liver were not affected. At
      383 MHz, exposure resulted in a significant transient increase in body weight up
      to 4%, while at 900 MHz this body weight increase was more pronounced (up to 6%)
      and not transient. At 1800 MHz, no effect on body weight was seen. The results
      corroborate earlier findings which have shown no effects of RF-EMF on melatonin
      levels in vivo and in vitro. The data are in accordance with the hypothesis that
      absorbed RF energy may result in metabolic changes which eventually cause body
      weight increases in exposed animals. The data support the notion that metabolic
      effects of RF-EMFs need to be investigated in more detail in future studies.

PMID- 18339123
TI  - Oxidative stress impairs oocyte quality and melatonin protects oocytes from free
      radical damage and improves fertilization rate.
AB  - We investigated the relationship between oxidative stress and poor oocyte quality
      and whether the antioxidant melatonin improves oocyte quality. Follicular fluid
      was sampled at oocyte retrieval during in vitro fertilization and embryo transfer
      (IVF-ET). Intrafollicular concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG)
      in women with high rates of degenerate oocytes were significantly higher than
      those with low rates of degenerate oocytes. As there was a negative correlation
      between intrafollicular concentrations of 8-OHdG and melatonin, 18 patients
      undergoing IVF-ET were given melatonin (3 mg/day), vitamin E (600 mg/day) or both
      melatonin and vitamin E. Intrafollicular concentrations of 8-OHdG and hexanoyl
      lysine adduct were significantly reduced by these antioxidant treatments. One
      hundred and fifteen patients who failed to become pregnant with a low
      fertilization rate (< or =50%) in the previous IVF-ET cycle were divided into two
      groups during the next IVF-ET procedure; 56 patients with melatonin treatment (3
      mg/day) and 59 patients without melatonin treatment. The fertilization rate was
      improved by melatonin treatment compared to the previous IVF-ET cycle. However,
      the fertilization rate was not significantly changed without melatonin treatment.
      Oocytes recovered from preovulatory follicles in mice were incubated with H2O2
      for 12 hr. The percentage of mature oocytes with a first polar body was
      significantly reduced by addition of H2O2 (300 microm). The inhibitory effect of
      H2O2 was significantly blocked by simultaneous addition of melatonin. In
      conclusion, oxidative stress causes toxic effects on oocyte maturation and
      melatonin protects oocytes from oxidative stress. Melatonin is likely to improve
      oocyte quality and fertilization rates.

PMID- 18339124
TI  - MT1 melatonin receptor internalization underlies melatonin-induced morphologic
      changes in Chinese hamster ovary cells and these processes are dependent on Gi
      proteins, MEK 1/2 and microtubule modulation.
AB  - Melatonin induces cellular differentiation in numerous cell types. Data show that
      multiple mechanisms are involved in these processes that are cell-type specific
      and may be receptor dependent or independent. The focus of this study was to
      specifically assess the role of human MT1 melatonin receptors in cellular
      differentiation using an MT1-Chinese hamster ovary (CHO) model; one that
      reproducibly produces measurable morphologic changes in response to melatonin.
      Using multiple approaches, we show that melatonin induces MT1-CHO cells to
      hyperelongate through a MEK 1/2, and ERK 1/2-dependent mechanism that is
      dependent upon MT1 receptor internalization, Gi protein activation, and clathrin
      mediated endocytosis. Using immunoprecipitation analysis, we show that MT1
      receptors form complexes with Gi(alpha) 2,3, Gq(alpha), beta-arrestin-2, MEK 1/2,
      and ERK 1/2 in the presence of melatonin. We also show that MEK and ERK activity
      that is induced by melatonin is dependent on Gi protein activation, clathrin
      mediated endocytosis and is modulated by microtubules. We conclude from these
      studies that melatonin-induced internalization of human MT1 melatonin receptors
      in CHO cells is responsible for activating both MEK 1/2 and ERK 1/2 to drive
      these morphologic changes. These events, as mediated by melatonin, require Gi
      protein activation and endocytosis mediated through clathrin, to form MT1
      receptor complexes with beta-arrestin-2/MEK 1/2 and ERK 1/2. The MT1-CHO model is
      invaluable to mapping out signaling cascades as mediated through MT1 receptors
      especially because it separates out MEK/ERK 1/2 activation by MT1 receptors from
      that of receptor tyrosine kinases.

PMID- 18339125
TI  - Effect of melatonin on apoptosis, proliferation and differentiation of urothelial
      cells after cyclophosphamide treatment.
AB  - Melatonin was recently shown to have protective effects against cyclophosphamide
      (CP)-induced hemorrhagic cystitis (HC) by diminishing bladder oxidative stress.
      HC is accompanied by destruction of the bladder urothelium and followed by
      apoptosis and rapid regeneration via proliferation and differentiation of
      urothelial cells, reaching complete restoration of normal urothelium in three
      weeks. Therefore, the effect of melatonin on apoptosis, proliferation and
      differentiation of urothelial cells, during destruction and regeneration of the
      urothelium three-weeks after a single dose CP treatment, was studied. F344 male
      rats were injected intraperitoneally with saline (control group) or melatonin
      (Mel group) or a single dose of CP (100 mg/kg; CP group) or melatonin (10 mg/kg)
      with CP (Mel + CP group). Melatonin co-treatment with CP significantly reduced
      apoptosis and increased proliferation of urothelial cells at day 1 and thus
      prevented extensive loss of cells from the urothelium. However, proliferation
      indices at days 4 and 7 after melatonin and CP co-treatment suddenly dropped and
      therefore the development of hyperplasia was prevented. Melatonin co-treatment
      with CP also resulted in earlier differentiation of superficial urothelial cells.
      Melatonin seems to have protective effect against CP-induced urothelial damage
      and a favorable impact on regeneration and restoration of normal urothelium,
      since it reduces the number of apoptotic and proliferating urothelial cells and
      results in their earlier differentiation.

PMID- 18339126
TI  - Effects of exogenous melatonin and circadian synchronization on tumor progression
      in melanoma-bearing C57BL6 mice.
AB  - Circadian rhythmicity impairment reportedly becomes significant as a tumor
      progresses, while the incidence of cancer can be affected by disruption of the
      circadian system. Melatonin has oncostatic effects on several types of cancer
      (breast, prostate, and colorectal cancers), while it can be self-defeating in
      others, such as lymphoma. Melanoma is one of the most aggressive cancers in
      humans; however, it seems to respond positively to melatonin in vitro. The
      present work tested whether body temperature (BT) rhythms are impaired by tumor
      progression, and whether exogenous melatonin restricts tumor growth and restores
      circadian rhythmicity; therefore, enhancing survival. To this end, C57 mice were
      intraperitoneal implanted with a temperature data logger and subcutaneously
      inoculated with melanoma cells. Animals were then submitted to light-dark (LD)
      12:12 cycles or continuous light (LL), with or without melatonin administration.
      Under LD light conditions, the BT rhythm exhibited a marked reduction in the
      first circadian harmonic amplitude, and increased phase instability (Rayleigh
      vector) as the tumor progressed. Melatonin administration (2 mg/kg BW/day), on
      the other hand, increased the BT rhythm amplitude and phase stability, reduced
      tumor weight and prevented intraperitoneal dissemination. Exposure to LL induced
      a free-running rhythm (1500 min), significantly increasing tumor malignity, and
      therefore reducing survival. Surprisingly, the highest tumor weights and
      morbidity by metastasis were seen in the LL group treated with melatonin probably
      because this indoleamine was being administered at different subjective hours to
      free-running animals. Circadian rhythmicity can thus be used as a marker rhythm
      for tumor progression, as rhythm impairment increases along with tumor
      malignancy. While melatonin administration improves rhythmicity and enhances
      survival under LD conditions, the results are self-defeating when they coexist
      with circadian disruption as it occurs under LL. This emphasizes the importance
      of taking into account endogenous rhythmicity and limiting melatonin
      administration to the subjective night in order to restrict melanoma progression.

PMID- 18339127
TI  - Melatonin antagonizes the intrinsic pathway of apoptosis via mitochondrial
      targeting of Bcl-2.
AB  - We have recently shown that melatonin antagonizes damage-induced apoptosis by
      interaction with the MT-1/MT-2 plasma membrane receptors. Here, we show that
      melatonin interferes with the intrinsic pathway of apoptosis at the mitochondrial
      level. In response to an apoptogenic stimulus, melatonin allows mitochondrial
      translocation of the pro-apoptotic protein Bax, but it impairs its
      activation/dimerization The downstream apoptotic events, i.e. cytochrome c
      release, caspase 9 and 3 activation and nuclear vesiculation are equally
      impaired, indicating that melatonin interferes with Bax activation within
      mitochondria. Interestingly, we found that melatonin induces a strong re
      localization of Bcl-2, the main Bax antagonist to mitochondria, suggesting that
      Bax activation may in fact be antagonized by Bcl-2 at the mitochondrial level.
      Indeed, we inhibit the melatonin anti-apoptotic effect (i) by silencing Bcl-2
      with small interfering RNAs, or with small-molecular inhibitors targeted at the
      BH3 binding pocket in Bcl-2 (i.e. the one interacting with Bax); and (ii) by
      inhibiting melatonin-induced Bcl-2 mitochondrial re-localization with the MT1/MT2
      receptor antagonist luzindole. This evidence provides a mechanism that may
      explain how melatonin through interaction with the MT1/MT2 receptors, elicits a
      pathway that interferes with the Bcl-2 family, thus modulating the cell
      life/death balance.

PMID- 18339128
TI  - Novel bromomelatonin derivatives suppress osteoclastic activity and increase
      osteoblastic activity: implications for the treatment of bone diseases.
AB  - The teleost scale is a calcified tissue that contains osteoclasts, osteoblasts,
      and bone matrix, all of which are similar to those found in mammalian membrane
      bone. Using the goldfish scale, we recently developed a new in vitro assay system
      and previously demonstrated that melatonin suppressed both osteoclastic and
      osteoblastic activities in this assay system. In mammals, 2-bromomelatonin
      possesses a higher affinity for the melatonin receptor than does melatonin. Using
      a newly developed synthetic method, we synthesized 2-bromomelatonin, 2,4,6
      tribromomelatonin and novel bromomelatonin derivatives (1-allyl-2,4,6
      tribromomelatonin, 1-propargyl-2,4,6-tribromomelatonin, 1-benzyl-2,4,6
      tribromomelatonin, and 2,4,6,7-tetrabromomelatonin) and then examined the effects
      of these chemicals on osteoclasts and osteoblasts. All bromomelatonin
      derivatives, as well as melatonin, had an inhibitory action on osteoclasts. In
      particular, 1-benzyl-2,4,6-tribromomelatonin (benzyl-tribromomelatonin) possessed
      a stronger activity than melatonin. At an in vitro concentration of 10(-10) m,
      benzyl-tribromomelatonin still suppressed osteoclastic activity after 6 hr of
      incubation. In reference to osteoblasts, all bromomelatonin derivatives had a
      stimulatory action, although melatonin inhibited osteoblastic activity. In
      addition, estrogen receptor mRNA expression (an osteoblastic marker) was
      increased in benzyl-tribromomelatonin (10(-7) m)-treated scales. Taken together,
      the present results strongly suggest that these novel melatonin derivatives have
      significant potential for use as beneficial drug for bone diseases such as
      osteoporosis.

PMID- 18339129
TI  - Fetal/placental regulation of maternal melatonin in rats.
AB  - We investigated how maternal melatonin is regulated in pregnant rats. To examine
      the involvement of the conceptus (fetus and placenta) in serum melatonin
      concentrations, the number of conceptuses was experimentally reduced to one on
      day 7 of pregnancy (1-conceptus group). Maternal circulating nighttime melatonin
      levels increased toward day 21 of pregnancy and rapidly decreased to the non
      pregnancy levels after parturition, whereas the maternal serum nighttime
      melatonin levels of the 1-conceptus group on day 21 of pregnancy were
      significantly lower than normal pregnancy bearing dams more than 10 conceptuses.
      When the fetuses were removed by fetectomy (all fetuses but not the placentae) on
      day 12 of pregnancy, serum melatonin concentrations were not decreased. To
      examine the source of circulating maternal melatonin, mRNA expression of N
      acetyltransferase (NAT), which is a late limiting enzyme for melatonin synthesis,
      was examined in the placenta and fetal pineal. NAT was not expressed in the
      placenta and was negligible in the pineal gland of the fetus compared with the
      mother's pineal gland. To examine the effect of placental hormones on maternal
      melatonin production, a conditioned medium, which was made by incubating placenta
      of day 20 of pregnancy with medium, was injected into the 1-conceptus dams from
      day 17 to day 20 of pregnancy. Injection of conditioned medium significantly
      increased serum melatonin concentrations compared with the control values whereas
      charcoal treatment abolished the stimulatory effect of conditioned medium. In
      conclusion, maternal circulating melatonin is from the maternal pineal gland and
      is increased by placental hormones during pregnancy.

PMID- 18339130
TI  - After discontinuation of calcineurin inhibitors, tapering of mycophenolate
      mofetil further impairs donor-directed cytotoxicity.
AB  - BACKGROUND: Recently, we described a significant decrease in donor-specific
      cytotoxic T-lymphocyte precursor frequency (CTLpf) after discontinuation of
      calcineurin inhibitors (CNI), while the proliferative capacity in mixed
      lymphocyte culture (MLC), and the number of interferon-gamma (IFN-gamma)
      producing cells (pc) in Elispot remained unchanged. METHODS: We tested T-cell
      reactivity in CNI free patients with stable renal graft function, on
      mycophenolate mofetil (MMF) or azathioprine (AZA) plus prednisone, who were
      tapered to 50% of their MMF or AZA dose. RESULTS: Furthermore, tapering of the
      MMF or AZA dose resulted in a decrease of donor-reactive CTLpf in all patients
      with detectable CTLpf. Detectable numbers decreased from a median of 32 to 8
      CTLp/10(6) peripheral blood mononuclear cell (PBMC). No effect on third-party
      reactive CTLpf was found, while the T-cell reactivity to donor and third-party
      cells as tested in MLC and in IFN-gamma Elispot was not affected either by
      tapering of immunosuppression. Third-party reactivity was significantly higher
      than donor-specific reactivity in all tests. A control group showed no changes in
      any of the in vitro assays. CONCLUSION: Both withdrawal of CNI and tapering of
      MMF or AZA dose decreases the donor-specific CTLpf. Our data suggest that
      reduction of immunosuppression results in a specific decrease of donor-directed
      cytotoxic capacity of immunocompetent cells, while their proliferation and
      cytokine production capacity remained unchanged. Immunosuppression hinders
      development of cytotoxic non-responsiveness.

PMID- 18339131
TI  - Recovery of renal function after 90 d on dialysis: implications for
      transplantation in patients with potentially reversible causes of renal failure.
AB  - BACKGROUND: Late recovery of renal function in patients requiring dialysis is a
      well recognized but uncommon phenomenon. Moves to increase the number of live
      donor transplants and the recognition that early transplantation is associated
      with better graft survival means it is possible that patients who are going to
      recover renal function may be transplanted unnecessarily. DESIGN: Prospective
      survey of patients receiving dialysis for more than 90 d in south west Scotland
      from 1 January 1994 to 31 December 2005. METHODS: Routine measurement of residual
      renal function by combined urea and creatinine clearance allowed us to detect
      late recovery whenever this occurred. RESULTS: Eight of 202 (4%) patients
      recovered sufficient renal function to stop dialysing after 90-d treatment. The
      likely cause of the renal failure in five of these patients was atheroembolism.
      One with atherosclerotic renovascular disease had been stented and would have
      received a live related renal transplant had his sister not had second thoughts
      about the procedure. CONCLUSION: It may be sensible to postpone transplantation
      in patients with certain types of renal failure, perhaps particularly patients
      with renovascular disease who have recently undergone a failed revascularization
      procedure.

PMID- 18339132
TI  - Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving
      tacrolimus-based immunosuppressive regimen.
AB  - Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive
      drugs with distinct safety profile. METHODS: Kidney transplant recipients
      receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to
      receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15
      mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy.
      RESULTS: No differences were observed in the incidence of the composite (biopsy
      confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p =
      1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient
      (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored
      graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL
      respectively. Patients receiving SRL showed worse safety outcomes, higher mean
      creatinine (1.6 +/- 0.5 mg/dL vs. 1.4 +/- 0.3 mg/dL, p = 0.007), higher
      proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean
      urinary protein concentrations (0.3 +/- 0.5 g/L vs. 0.1 +/- 0.2 g/L, p = 0.012),
      higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and
      higher proportion of patients prematurely discontinued from randomized therapy
      (26% vs. 8%, p = 0.031). CONCLUSION: In patients receiving TAC, MMF produced
      similar efficacy but superior safety profile compared with SRL.

PMID- 18339133
TI  - Age and heart transplantation: results from a heart failure management unit.
AB  - BACKGROUND: More evidence is needed to assess the pros and cons of maintaining
      age-limit policies in heart transplantation (HT). METHODS: We analyzed clinical
      data from a heart failure management unit to investigate the impact of age on
      prognosis of two distinct cohorts: (i) 309 patients (median age, 57 yr; 62% male)
      with severe chronic heart failure (CHF) consecutively screened for HT; (ii) 336
      HT recipients (median age 56 yr, 82% male). RESULTS: In CHF patients (screened
      for HT), prognosis was conditioned by the underlying severity of cardiac disease
      (i.e., New York Heart Association class III-IV, decreasing blood pressure,
      presence of atrial fibrillation and severe mitral regurgitation), whereas
      increasing age showed no sign of predicting all-cause or cardiovascular mortality
      (both p > or = 0.4). In HT recipients, age did not retain significance at
      multivariate analysis as an independent predictor (p > or = 0.14 for both all
      cause and cardiovascular death), whereas ischemic etiology of pre-existing CHF
      did (p < or = 0.02). CONCLUSIONS: Age did not appear to be a primary determinant
      of all-cause or cardiovascular mortality among potential HT candidates or
      eventual recipients (ischemic etiology of CHF turned out to be the major
      determinant of post-transplant outcome). These results support the concept that
      HT may be considered a treatment option in patients with more advanced age
      strata, particularly when affected by non-ischemic cardiomyopathy.

PMID- 18339134
TI  - Influence of angiotensin I-converting enzyme polymorphism on development of post
      transplant erythrocytosis in renal graft recipients.
AB  - BACKGROUND: Post-transplant erythrocytosis (PTE) is estimated at 5-20%.
      Angiotensin II generated by angiotensin I-converting enzyme (ACE) stimulates
      erythropoiesis. The highest activity of ACE is observed in DD genotype. The
      question arises if ACE gene polymorphism influences PTE. METHODS: One-year
      prospective study included 89 kidney recipients (28 women and 61 men). RESULTS:
      Thirty-four (38%) recipients proved to be DD genotype, 36 (40%) ID, and 19 (22%)
      II genotype. Absolute PTE [hematocrit level (HCT) >50% and RBC > 5.5 mln/mm(3)]
      was found in 14 (19%) patients. PTE developed 6-12 months after kidney Tx. There
      were no significant differences in genotype distribution between patients with
      and without PTE. ANOVA showed that the most significant predictor of PTE
      development was the time since kidney Tx (p < 0.0001). Analysis of logistic
      regression showed that male sex was the most important factor in PTE development
      12 months after kidney Tx (OR = 13.6: 95% CI 1.2-150.9, p < 0.05). D allele
      increased the PTE risk (OR = 3.3 for each allele: 95% CI 1.1-10.4, p < 0.05), the
      use of angiotensin-converting enzyme inhibitors (ACEI) decreased the PTE risk (OR
      = 0.15: 95% CI 0.03-0.85, p < 0.05). In patients with DD genotype, there was a
      correlation between hemoglobin, RBC and HCT concentration, 12 months after Tx and
      panel of reactive antibody value before Tx (Rs = +0.43, p < 0.05). CONCLUSIONS:
      Male sex and D allele presence increase the risk of PTE development, especially
      in highly immunized patients. The use of ACEI decreases the risk of PTE
      development.

PMID- 18339135
TI  - Emergence of drug-resistant cytomegalovirus in the era of valganciclovir
      prophylaxis: therapeutic implications and outcomes.
AB  - BACKGROUND: Valganciclovir prophylaxis is reportedly associated with a low
      incidence of ganciclovir-resistant cytomegalovirus (CMV). We assessed the
      incidence, clinical features, and outcome of drug-resistant CMV among solid organ
      transplant patients who received valganciclovir prophylaxis. METHODS: The medical
      records of all CMV D+/R- kidney, pancreas, liver, and heart recipients were
      screened for CMV disease, and the clinical course and outcomes of patients with
      drug-resistant CMV were reviewed. RESULTS: During a four-yr-study period, a total
      of 225 CMV D+/R- transplant patients received valganciclovir prophylaxis for a
      median of 92 d. Sixty-five (29%) of the 225 patients developed delayed-onset
      primary CMV disease, including nine (14%) suspected to have drug-resistant virus.
      Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient
      manifested gastrointestinal tissue-invasive disease. Together with reduction in
      immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin
      was the most common treatment. Drug-associated nephrotoxicity was commonly
      observed and resulted in allograft loss in two patients. During the mean follow
      up of 2.2 yr, allograft loss and mortality occurred in two of four patients with
      proven and in three of five patients with clinically suspected drug-resistant
      CMV. CONCLUSIONS: Cytomegalovirus disease because of clinically suspected or
      genotypically confirmed drug-resistant CMV is not uncommon in CMV D+/R- solid
      organ transplant patients who received valganciclovir prophylaxis. Because of its
      significant morbidity and mortality, an optimized strategy of CMV prevention is
      warranted to reduce the negative impact of drug-resistant CMV on the successful
      outcome of organ transplantation.

PMID- 18339136
TI  - The outcome of primary liver transplantation from deceased donors in children
      with body weight < or =10 kg.
AB  - Between November 1982 and March 2006, 67 children with body weight < or =10 kg
      had a primary liver transplantation from deceased donors in our unit. The aim of
      this study was to analyze the outcome in terms of patient and graft survival and
      to search for factors affecting this outcome. Overall, one-, three-, five-, and
      10-yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%,
      56%, 53%, 48%, respectively. Twenty-four of 67 (36%) children died and in the
      remaining 22 (33%), the first grafts failed and they were retransplanted. Cox
      regression analysis revealed that a need for retransplantation and urgent
      transplantation were important predictors for patient survival (p = 0.04 and p =
      0.001, respectively). To assess whether the need for retransplantation can be
      influenced, all study variables were compared between surviving grafts and failed
      grafts. Cox regression analysis showed that only donor/recipient (D/R) weight
      ratio proved to be independent predictor for graft survival (p = 0.004). After
      comparison of graft survival with the long rank test according to different D/R
      weight ratios (3.0-7.0), the cut-off point for significantly different graft
      survival approached 4.0. The one-, three-, five-, and 10-yr graft survival for
      technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68%
      compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p
      = 0.02). In summary, patient survival in children with body weight < or =10 kg is
      determined by urgent transplantation and the need for retransplantation. Graft
      loss and retransplantation in small children can be prevented by adequate size
      matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer
      the favorable outcome.

PMID- 18339137
TI  - Liver transplantation in a subject with familial hypercholesterolemia carrying
      the homozygous p.W577R LDL-receptor gene mutation.
AB  - Mutations within the low density lipoprotein (LDL)-receptor gene result in
      familial hypercholesterolemia, an autosomal dominant inherited disease. Clinical
      homozygous affected subjects die of premature coronary artery disease as early as
      in early childhood. We identified a girl at the age of five yr with clinical
      homozygous familial hypercholesterolemia presenting with achilles tendon
      xanthomas and arcus lipoides. Her total cholesterol reached up to 1050 mg/dL.
      Molecular characterization of the LDL-receptor gene revealed a homozygous p.W577R
      mutation. Despite intensive treatment interventions with the combination of diet,
      statins, colestipol, and LDL-apheresis, the patient developed symptomatic
      coronary artery disease at the age of 16 yr. Subsequently, orthotopic liver
      transplantation was performed to cure the defective LDL-receptor gene. Clinical
      follow-up for almost nine yr post-transplantation revealed excellent liver
      function, normal liver enzymes, normal LDL-cholesterol, and regression of both
      tendon xanthomas and symptomatic coronary artery disease. In conclusion, liver
      transplantation can effectively reduce LDL-cholesterol in a familial
      hypercholesterolemia recipient with subsequent regression of xanthomas and
      atherosclerosis. Timing is extremely important in these exceptional cases to
      exclude the demand for heart transplantation due to severe coronary artery
      disease. In addition, the identification of the LDL-receptor as etiology of
      clinical homozygous hypercholesterolemia is a prerequisite once liver
      transplantation is considered as therapeutic option.

PMID- 18339138
TI  - Arteriovenous fistula reconstruction in patients with kidney allograft failure.
AB  - BACKGROUND: Kidney recipients with failing allograft function face the vascular
      access problem again before returning to hemodialysis. An autologous
      arteriovenous fistula (AVF), according to the recent Kidney Disease Outcomes
      Quality Initiative (KDOQI) guidelines, is the optimal vascular access and the use
      of prosthetic grafts and catheters should be limited. The objective of this study
      was to assess the feasibility of AVF reconstruction in patients reentering
      hemodialysis after kidney allograft failure. MATERIALS AND METHODS: Two hundred
      and forty-one transplant recipients reentered hemodialysis between 1990 and 2005.
      Before kidney transplantation, 221 patients had a functioning AVF on the forearm.
      Fistula reconstruction was attempted in 112 (51%) patients because of AVF
      thrombosis. Three strategies were applied according to forearm vein patency: a
      new radial-cephalic fistula, a radial-perforating vein fistula, or a radial
      basilic forearm transposition was created. RESULTS: Forearm AVFs were
      successfully reconstructed in 85 of the 112 patients (73%). The primary patency
      of the reconstructed AVFs was 57.6% and 44% at 12 and 24 months. Secondary
      patency was 64.9% and 54.9% at 12 and 24 months, respectively. CONCLUSIONS: The
      reconstruction of an old, thrombosed AVF is possible in kidney recipients
      returning to dialysis, even if the time from thrombosis to fistula repair is a
      few years.

PMID- 18339139
TI  - Low incidence of secondary neoplasia after autotransplantation for
      lymphoproliferative disease: the role of pre-transplant therapy.
AB  - To asses the real contribution of pre-transplantation treatment in the incidence
      of secondary neoplasia after autologous transplant for lymphoproliferative
      disorders, we used stringent inclusion/exclusion criteria. One hundred and forty
      two patients out of 323 that underwent autologous transplantation for
      lymphoproliferative disorders were studied. The risk factors that were evaluated
      with univariate and multivariate analysis included: gender, sex, age, diagnosis,
      radiotherapy, and chemotherapy prior to conditioning regimen, disease status at
      peripheral blood stem-cell transplantation (PBSCT) and type of harvest. Three
      patients developed secondary myelodysplastic syndrome/acute myeloid leukemia
      (sMDS/AML) and three patients developed solid neoplasia. By univariate analysis
      diagnosis chronic lymphocytic leukemia and use of fludarabine and monoclonal
      antibodies were the only variables significantly associated with the development
      of sMDS/AML. By multivariate analysis, the variables associated with sMDS/AML
      were the use of fludarabine and disease status at PBSCT. By univariate analysis,
      we found that radiotherapy and the use of monoclonal antibodies were
      significantly associated with the development of secondary solid neoplasia.
      Multivariate analysis confirmed that the only two variables significantly
      associated with new cancers were radiotherapy and prior treatment with monoclonal
      antibodies. We report the lowest incidence of sMDS/AML after autologous stem-cell
      transplantation for lymphoproliferative malignancies. Major reasons could be
      ascribed to the stringent inclusion/exclusion criteria used to establish the real
      incidence of sMDS/AML because of chemo-radiotherapy used before transplant
      procedure. The low incidence of secondary solid tumors could be caused by the
      absence of total body irradiation as part of the conditioning regimen or the
      short follow-up.

PMID- 18339140
TI  - A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance
      immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow
      up.
AB  - INTRODUCTION: A long-term prospective randomized trial evaluating alemtuzumab, a
      humanized anti-CD52 monoclonal antibody, in a predominantly non-Caucasian
      population has yet to be reported. METHODS: Ninety deceased donor (DD) first
      renal transplant recipients were randomized into three different antibody
      induction groups: group A, thymoglobulin (Thymo); group B, alemtuzumab; group C,
      daclizumab (Dac). In groups A and C, the target trough levels of tacrolimus were
      8-10 ng/mL, mycophenolate mofetil (MMF) 1 g administered twice daily, and
      maintenance methylprednisolone. In group B, target tacrolimus trough levels were
      4-7 ng/mL, 500 mg MMF administered twice-daily, without methylprednisolone.
      African-Americans and Hispanics comprised more than 50% in each group. RESULTS: A
      minimum follow-up of 27 months showed no overall group differences in patient or
      graft survival (p = 0.89 and 0.66), but a trend towards worse death-censored
      graft survival in group B (p = 0.05). Acute rejection rates were not
      significantly different: six (20%), seven (23%), and seven (23%) in groups A, B,
      and C, respectively. The incidence of chronic allograft nephropathy was higher in
      group B than in A and C (p = 0.008). The mean calculated creatinine clearance at
      24 months was 81.1 +/- 5.5, 64.4 +/- 4.5, and 80.7 +/- 5.7 in groups A, B, and C,
      respectively (p = 0.01 for B vs. average of A and C). CONCLUSION: In this
      randomized 27-month minimum follow-up trial of predominantly non-Caucasian DD
      renal transplant recipients with alemtuzumab induction, lower maintenance
      tacrolimus, MMF, and steroid avoidance appear less effective than either Thymo or
      Dac with higher maintenance immunosuppression.

PMID- 18339141
TI  - Attitude of health care professionals to brain death: influence on the organ
      donation process.
AB  - BACKGROUND: The acceptance and application of the concept that brain death is a
      valid determination of death is the central issue in organ donation. However,
      whether attitude to brain death of health care professionals influences the organ
      procurement process has not been systematically studied. METHODS: Questionnaires
      were distributed to health care professionals involved in the organ procurement
      process (intensive care, internal medicine, emergency room, anesthesia) in all
      hospitals in Israel. Attitude to brain death (defined as positive if the
      respondent accepted brain death as a valid determination of death, negative or do
      not know) and level of comfort in performing key donor-related tasks were
      analyzed. RESULTS: A total of 2366 completed questionnaires were returned (629
      doctors and 1737 nurses; response rate 60.3%). Overall, 78.9% of respondents had
      a positive attitude to brain death. This was significantly associated with
      increasing age, higher professional status and was most prevalent amongst
      intensive care unit staff (p < 0.001 for all variables). These respondents felt
      significantly more comfortable informing the transplant coordinator of a
      potential donor, explaining brain death to the family, raising the subject of
      organ donation, approaching the family about donation and providing support to
      the grieving family. In addition, they believed the transplant coordinator should
      be involved early in the donation process. CONCLUSIONS: The understanding and
      acceptance of brain death as a valid determination of death was associated with a
      positive effect on the level of comfort of health care professionals in
      performing key donor-related tasks. Reinforcing a positive attitude to brain
      death among health care professionals may facilitate the procurement process.

PMID- 18339142
TI  - A single-center experience with liver transplantation for Wilson's disease.
AB  - Wilson's disease is an inherited disorder of copper metabolism, presenting with
      prominent hepatic and neurologic manifestations. There is an established place
      for liver transplantation in the presence of liver disease, while the indication
      for neurologic manifestations is debated. Between 1993 and 2005, 11 patients were
      liver transplanted for Wilson's disease at our institution. We retrospectively
      reviewed the medical records of the patients. The pathology of the explanted
      livers was analyzed. The patients were divided into three groups based on the
      evolution of the disease. Postoperative data gathered included patient and graft
      outcome, complications, neurologic status, and copper metabolism. Six males and
      five females were transplanted at a mean age of 29.7 yr (range 15-48 yr). Three
      patients had a fulminant presentation, two patients had decompensation of
      established disease, and six patients had chronic disease. Neurologic features
      were prominent in five patients. The pathologic analysis of the explanted graft
      showed cirrhosis in all patients. The five patients with fulminant and acute on
      chronic presentations also showed necrosis in the explant. The mean postoperative
      follow-up was 56.8 months (range 10-129 months). Two patients were re
      transplanted. One patient died because of severe sepsis. Two patients with severe
      neurologic dysfunction showed significant remission of symptoms. Liver
      transplantation is a safe and effective treatment for both acute and chronic
      presentations of Wilson's disease. Acute presentation correlates with the
      presence of necrosis in the explanted liver. In our series, there was a relevant
      improvement of the neurologic features after transplantation.

PMID- 18339143
TI  - Cytomegalovirus viremia in solid organ transplantation: does the initial viral
      load correlate with risk factors and outcomes?
AB  - Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to
      predict outcomes after solid organ transplantation (SOT) are lacking. Recipients
      with measurable CMV QnPCR and either CMV-V (asymptomatic viremia) or CMV-D
      (symptomatic CMV infection) were analyzed over 24 months. Risk factors and
      outcomes were evaluated in relation to initial QnPCR by regression analysis and
      time-to-event curves. Twenty-eight recipients were identified: five CMV-V, 23 CMV
      D. Patients with CMV-D had a higher median initial QnPCR (230 000 copies/mL)
      compared with CMV-V (2500 copies/mL; p < 0.05). No patients with CMV-V had an
      initial QnPCR > 10 000 copies/mL compared with 83% of the CMV-D (p = 0.004). The
      initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV
      PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03).
      Risk factors and indirect CMV effects were not associated with initial QnPCR. Our
      results highlight the importance of the initial CMV QnPCR in relation to the
      development of symptomatic CMV and a slower response to therapy. Alternatively,
      late asymptomatic viremia and recurrent CMV are associated with lower PCR levels
      and a low likelihood to progress and result in clinical disease.

PMID- 18339144
TI  - Cardiovascular risk, cardiovascular events, and metabolic syndrome in renal
      transplantation: comparison of early steroid withdrawal and chronic steroids.
AB  - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death with a
      functioning graft in renal transplant recipients. The purpose of this study was
      to compare Framingham Risk Score (FRS), metabolic syndrome (MS), and
      cardiovascular events (CVE) in patients receiving early corticosteroid withdrawal
      (ECSWD), or chronic corticosteroid therapy (CCS). METHODS: In all, 251 ECSWD and
      146 CCS patients were evaluated. FRS and MS were identified at baseline, six, 12,
      and 24 months post-transplant. A total of 124 patients with diabetes mellitus
      prior to transplantation were excluded from MS analysis. CVE were defined as
      sudden-death, MI, angina, or CVA/TIA. Repeat-measure logistic regression was used
      for statistical analysis. RESULTS: Fifty-four patients experienced 72 CVE. Mean
      follow-up was 755 +/- 312 d and time to CVE was 14.8 +/- 8.3 months. Demographics
      were similar between groups. FRS was not different between groups. CVE were
      significantly greater in CCS patients then ECSWD (20% vs. 10%, p = 0.024). New
      onset MS occurred more frequently in patients receiving CCS then ECSWD (45% vs.
      22%, p < 0.001) and was associated with more CVE (p < 0.015). CONCLUSIONS:
      Patients receiving ECSWD regimens have significantly decreased CVE and new onset
      MS compared with CCS. MS is associated with increased CV risk and CVE.

PMID- 18339145
TI  - Thrombotic microangiopathy following pancreas after kidney transplants.
AB  - Advances in immunosuppressive therapy and refinement in surgical techniques have
      allowed pancreas after kidney (PAK) transplantation to become a viable
      therapeutic option for patients with brittle type I diabetic recipients of a
      living donor or previous deceased kidney alone transplant. Although maintenance
      immunosuppressive therapy is not significantly changed after the addition of a
      pancreas, a temporary booster in immunosuppressive therapy and an increase in the
      dose of calcineurin inhibitor (CNI) are required after PAK transplantation. The
      latter has been implicated in the observed variable decline in kidney allograft
      function. We herein report two cases of kidney allograft dysfunction following
      PAK transplant due to biopsy-proven transplant, thrombotic microangiopathy (TMA).
      Whether PAK transplantation pre-disposes a subset of patients to the development
      of post-transplant TMA is not known. Diagnostic kidney biopsies should be
      considered in PAK transplant recipients with worsening kidney allograft function.

PMID- 18339146
TI  - Diabetic gastroparesis-associated bezoar resolution via "cola-lysis".
AB  - Phytobezoars associated with diabetic gastroparesis are often sources of
      diminished quality of life for patients. Poor blood sugar control has been
      associated with increasing gastroparesis. For recipients of pancreas transplants
      to correct diabetes, phytobezoar treatment post-transplant can typically be
      limited to invasive procedures and prokinetic agents. We present the case of an
      alternative treatment to phytobezoar, cola libation, i.e., "cola-lysis."

PMID- 18339147
TI  - Cytomegalovirus infection and new-onset post-transplant diabetes mellitus.
AB  - We analyzed data from all consecutive kidney transplant patients at our
      institution between April 2003 and October 2006. We found 15 cases of late-onset
      cytomegalovirus (CMV) infection, two of which developed concurrent post
      transplant diabetes mellitus (PTDM). In these two cases, PTDM was transient and
      normal glucose tolerance was achieved after an eight-wk therapeutic course of
      oral valganciclovir. These findings suggest that CMV infection after organ
      transplantation may be associated with concurrent PTDM. The distinct causative
      relationship is yet to be determined.

PMID- 18339148
TI  - Use of low dose tacrolimus, mycophenolate mofetil and maintenance IL-2 receptor
      blockade in an islet transplant recipient.
AB  - The utilization of dual maintenance therapy with tacrolimus and sirolimus (the
      Edmonton protocol) has been widely adopted as standard immunosuppression for
      islet cell transplantation. This immunosuppression regimen has numerous
      toxicities including renal dysfunction, anemia, and recurrent aphthous ulcers. We
      present a case of a 63-yr-old Caucasian female who received an isolated islet
      transplant. Over the first six months post-transplant, the patient developed
      severe anemia, intractable aphthous ulcers, and renal dysfunction. Islet
      transplant function was excellent and the patient is insulin-independent since
      the end of the second month post-transplant. However, because of the above
      toxicities, a decision was made to change her immunosuppression regimen eight
      months post-transplant to low dose tacrolimus, mycophenolate mofetil, and a
      monthly maintenance infusion of daclizumab. Since then, her aphthous ulcers have
      disappeared, renal function has improved, and islet cell function remains stable.

PMID- 18339149
TI  - Generalized lymphedema in a sirolimus-treated renal transplant patient.
AB  - Generalized lymphedema is an extremely rare effect of sirolimus therapy in renal
      transplant recipients. We describe the development of this complication in a 56
      yr-old woman, who was given an experimental protocol with cyclosporine,
      sirolimus, steroids, and basiliximab. Following the protocol, after one month,
      the patient was randomized to the "sirolimus only" group, while cyclosporine was
      completely suspended and the oral steroids were continued. Three months later,
      the patient was admitted for severe lymphedema of the lower limbs, with
      significant weight increase, massive ascites and dyspnea, but excellent renal
      function. A chest radiography and an ultrasound study of the heart showed a
      moderate pleural and pericardial effusion. An abdominal ultrasound scan showed
      two small lymphoceles next to the transplanted kidney, confirmed with a CT scan.
      After sirolimus discontinuation the generalized lymphedema started to improve and
      three months later all the symptoms had disappeared.

PMID- 18339150
TI  - The ketamine enigma.

PMID- 18339151
TI  - Regional anesthesia meets ultrasound: a specialty in transition.
AB  - Despite its well-known benefits, regional anesthesia has not attained the
      stature, simplicity, and safety of general anesthesia. Many of the challenges and
      clinical failures of regional anesthetic techniques can be attributed to fact
      that neurovascular anatomy is highly variable. Furthermore, current nerve
      localization techniques provide little or no information regarding the anatomical
      spread local anesthesia. Recently, ultrasound technology has been utilized by
      anesthesiologists in an attempt to minimize many of the drawbacks of traditional
      nerve block techniques. This review article will update the reader on the current
      status of ultrasound-guided regional anesthesia, provide an evidence-based
      context, and supply key facts regarding ultrasound physics. In the process, we
      will also highlight several possible limitations of ultrasound techniques
      including learning curve issues, costs, and artifact generation.

PMID- 18339152
TI  - Severity scoring in the ICU: a review.
AB  - BACKGROUND: Patients in the intensive care unit (ICU) require huge resources
      because of the dysfunction of several of their vital organs. The heterogeneity
      and complexity of the ICU patient have generated interest in systems able to
      measure severity of illness as a method of predicting outcome, comparing quality
      of-care and stratification for clinical trials. METHODS: By searching Medline and
      EMBASE for publications describing scoring systems in the ICU, the most
      frequently used systems, defined as resulting in more than 50 references, are
      included in this review. Scoring systems belong to one of four classes
      prognostic, single-organ failure, trauma scores and organ dysfunction (OD). The
      different systems are described and discussed. RESULTS: Three different
      prognostic scoring systems, including several versions, four single OD scores and
      three OD scores, were included in this review. CONCLUSION: Different forms of
      scoring systems are frequently used in the ICU. They have become a necessary tool
      to describe ICU populations and to explain differences in mortality. As there are
      several pitfalls related to the interpretation of the numbers supplied by the
      systems, they should not be used without knowledge on the science of severity
      scoring.

PMID- 18339153
TI  - No morphine sparing effect of ketamine added to morphine for patient-controlled
      intravenous analgesia after uterine artery embolization.
AB  - BACKGROUND: Pain following embolization of the uterine arteries (UAEs) is
      variable and may be very severe requiring large doses of parenteral opioids for
      relief. The present study tested the hypothesis that the addition of ketamine to
      i.v. patient-controlled morphine reduces the amount of morphine required for pain
      control during the first 24 h after UAE embolization. METHODS: Fifty-six patients
      undergoing UAE embolization for treatment of symptomatic uterine leiomyomata were
      randomized to receive either 2 mg/ml of morphine (Control group, n=30) or 2 mg/ml
      of both morphine and ketamine (Ketamine group, n=26) by i.v. patient-controlled
      analgesia (IV-PCA). Pump settings were bolus dose 1 ml, lockout 10 min, no
      background infusion. In addition, all patients received diclofenac and
      acetaminophen for pain relief. Pain scores, morphine consumption and adverse
      events like nausea, vomiting, itching, visual disturbances, anxiety, dreaming and
      hallucinations, if any, were recorded for 24 h after embolization. RESULTS: The
      mean +/- SD 24-h consumption of patient-controlled morphine was 38.3 +/- 21.0 mg
      in the Ketamine group vs. 33.3 +/- 18.3 mg in the Control group (NS). The
      difference between the means was 5.0 mg (95% confidence interval: -5.7; 15.6).
      One patient in the Ketamine group vs. none in the Control group experienced
      auditory hallucinations. CONCLUSION: Studying an unselected group of patients
      undergoing embolization of the UAEs for treatment of symptomatic uterine
      leiomyomata under conditions of basal analgesia with acetaminophen and
      diclofenac, we failed to demonstrate any morphine-sparing effect of IV-PCA
      ketamine and morphine compared with IV-PCA morphine alone.

PMID- 18339154
TI  - Perioperative concentrations of catecholamines in the cerebrospinal fluid and
      plasma during spinal anesthesia.
AB  - BACKGROUND: Catecholamine release is a physiological response to stress. The
      extent to which perioperative stress provokes the central release of
      catecholamines, which modulate pain perception in the spinal cord, still remains
      unknown. The perioperative course of catecholamine concentrations in the
      cerebrospinal fluid (CSF) and plasma was examined. METHODS: A prospective study
      was performed in 25 patients (ASA III, 60-84 years) undergoing elective hip joint
      replacement in spinal catheter anesthesia. The concentrations of dopamine,
      epinephrine and norepinephrine in the CSF and plasma were measured before
      anesthesia, immediately after surgery, and 6 and 24 h post-operatively. RESULTS:
      In most patients, dopamine and epinephrine were not detectable in CSF. CSF
      norepinephrine concentrations decreased from median [interquartile-range] 159
      [124;216] pre-anesthesia to 116 [79;152] pmol/l immediately post-operatively and
      were slightly elevated 24 h post-operatively (180 [134;302] pmol/l) (P=0.05).
      Dopamine plasma concentrations were not detectable or were barely above the
      detection threshold. Plasma epinephrine increased from 61 [28;77] pmol/l pre
      anesthesia to 112 [69;138] pmol/l 6 h post-operatively and returned to baseline
      24 h post-operatively (P=0.001). Plasma norepinephrine concentrations increased
      intra-operatively from 298 [249;422] to 556 [423;649] pmol/l and remained
      elevated 24 h after surgery (P=0.009). There was no association between changes
      in CSF or plasma norepinephrine or epinephrine concentrations and changes in
      heart rate (HR) or mean arterial pressure (MAP). CONCLUSION: During spinal
      anesthesia for elective hip joint replacement, norepinephrine concentrations were
      greater in plasma than in CSF. CSF dopamine and epinephrine concentrations were
      essentially undetectable. The changes in CSF-norepinephrine concentrations and
      the changes of plasma norepinephrine concentrations showed no association with
      each other; nor were there correlations between clinical stress parameters (HR,
      MAP) or visual analog scale pain, and the changes in CSF norepinephrine
      concentrations.

PMID- 18339155
TI  - Interaction between a NMDA receptor antagonist, AP-5 and an AMPA receptor
      antagonist, YM 872 in antinociception in the spinal cord.
AB  - BACKGROUND: The intrathecal N-methyl-D-aspartate (NMDA) receptor antagonist, AP-5
      and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor
      antagonist, YM 872 showed inhibition on both acute and facilitated nociception in
      our previous study. The present study was performed to investigate the
      interaction between intrathecal AP-5 and YM 872 in antinociception for acute and
      chronic nociception. METHODS: Sprague-Dawley rats with lumbar intrathecal
      catheters were tested for their thermal tail withdrawal response and for their
      paw flinches by formalin injection after intrathecal administration of AP-5 or YM
      872. The effects of the combination were tested by an isobolographic analysis
      using 50% effective dose (ED50). Total fractional dose was calculated as (ED50
      dose of AP-5 in combination)/(ED50 dose of AP-5 alone)+(ED50 dose of YM 872 in
      combination)/(ED50 dose of YM 872 alone). RESULTS: Intrathecally administered AP
      5, YM 872, and their combination produced dose-dependent increases of the tail
      flick latency and decreases in the number of flinches in both phase 1 and 2 of
      the formalin test. The ED50 values of the combination were significantly lower
      than the calculated additive values (P<0.01). Total fractional dose value was
      0.22 in the tail flick test, 0.12 in the phase 1 and 0.14 in the phase 2 of the
      formalin test. CONCLUSION: An NMDA receptor antagonist, AP-5 and an AMPA receptor
      antagonist, YM 872 had synergistic antinociceptive effects on both acute thermal
      and inflammatory induced acute and facilitated nociception.

PMID- 18339156
TI  - N-Methyl-D-aspartate receptor antagonist MK-801 attenuates morphine tolerance and
      associated glial fibrillary acid protein up-regulation: a proteomic approach.
AB  - BACKGROUND: It is well known that long-term morphine administration results in
      tolerance, which limits the clinical use of this drug in pain management.
      METHODS: Male Wistar rats were randomly assigned to receive one of four different
      infusions: morphine [15 microg/h, intrathecal (i.t.)], saline, MK-801 (5
      microg/h, i.t.) plus morphine (15 microg/h, i.t.), or MK-801 (5 microg/h, i.t.)
      alone. RESULTS: Morphine infusion induced a maximal antinociceptive effect on day
      1 and tolerance on day 3, and the maximal anti-receptive tolerance was observed
      on day 5. Co-infusing MK-801 with morphine attenuated morphine's anti-receptive
      tolerance. Two-dimensional gel electrophoretic analysis of spinal proteins
      revealed that eight protein spots were up-regulated in morphine-tolerant rats,
      and that they were significantly inhibited by MK-801 co-infusion. Among the up
      regulated proteins, glial fibrillary acid protein (GFAP), a glial-specific maker,
      was identified by mass spectrometry. This finding was also confirmed by Western
      blot analysis. CONCLUSION: Using proteomic analysis, we identified eight GFAP
      protein spots that were up-regulated in the dorsal horn of morphine-tolerant rat
      spinal cords. This up-regulation was partly inhibited by N-methyl-D-aspartate
      receptor antagonist MK-801 co-infusion, which suggests that GFAP protein can be
      considered to be a pathogenesis marker of morphine tolerance.

PMID- 18339157
TI  - Blood volume is normal after pre-operative overnight fasting.
AB  - BACKGROUND: Pre-operative fasting is assumed to cause a deficit in intravascular
      blood volume (BV), as a result of ongoing urine production and insensible
      perspiration. Standard regimes consist of volume loading prior or simultaneous to
      any anaesthetic procedure to minimise the risk of hypotension. However, fluid
      overload in the context of major abdominal surgery has been shown to deteriorate
      patient outcome. Our study aimed to quantify total intravascular BV after fasting
      by direct measurements and to compare it with calculated normal values in
      comparable non-fasted patients. METHODS: After 10 h of fasting, total plasma
      volume (PV) and red cell volume (RCV) were measured via the double-label
      technique (indocyanine green dilution and erythrocytes labelled with fluorescein,
      respectively) following induction of general anaesthesia in 53 gynaecological
      patients suffering from malignoma of the cervix. The corresponding normal values
      were calculated individually from age, body height and body weight. RESULTS:
      Measured BV, RCV and PV after fasting were 4123+/-589, 1244+/-196 and 2879+/-496
      ml, respectively. The differences to the corresponding calculated normal values
      were not significant (3882+/-366, 1474+/-134 and 2413+/-232 ml, respectively).
      The measured haematocrit reflected a slight anaemic state (0.35+/-0.03).
      CONCLUSION: Our data suggest that even after prolonged pre-operative fasting,
      cardio-pulmonary healthy patients remain intravascularly normovolaemic.
      Therefore, hypotension associated with induction of general or neuraxial
      anaesthesia should perhaps be treated with moderate doses of vasopressors rather
      than with undifferentiated volume loading.

PMID- 18339158
TI  - Bupivacaine inhibits COX-2 expression, PGE2, and cytokine production in endotoxin
      activated macrophages.
AB  - BACKGROUND: Upregulation of cyclooxygenase-2 (COX-2) and resultant prostaglandin
      E(2) (PGE(2)) overproduction has been shown to play a crucial role in initiating
      a systemic inflammatory response during sepsis. Sepsis also induces robust
      production of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta), and IL-6 as well as anti-inflammatory cytokine IL
      10. We sought to elucidate the effects of bupivacaine on COX-2 expression and
      production of PGE(2) and cytokines using an endotoxin-activated murine
      macrophages model. METHODS: Confluent murine macrophages (RAW264.7 cells) were
      treated with lipopolysaccharide (LPS, 100 ng/ml) or LPS plus bupivacaine (1, 10,
      or 100 microM). Bupivacaine was added immediately after LPS. After reacting for
      18 h, cell cultures were harvested for subsequent analysis. RESULTS: LPS
      significantly upregulated COX-2 transcription and PGE(2) production in
      macrophages. LPS also significantly increased the production of TNF-alpha, IL
      1beta, IL-6 and IL-10 in macrophages. Bupivacaine significantly inhibited the
      effects of LPS on COX-2 transcription and PGE(2) production in a dose-dependent
      manner. In a dose-dependent manner, bupivacaine also significantly inhibited the
      effects of LPS on the production of TNF-alpha, IL-1beta, and IL-6. However,
      bupivacaine exerted no significant effects on LPS-induced IL-10 production.
      CONCLUSION: Bupivacaine significantly inhibited COX-2 expression, PGE(2) and
      cytokine production in endotoxin-activated macrophages.

PMID- 18339159
TI  - Goal-directed fluid therapy: stroke volume optimisation and cardiac dimensions in
      supine healthy humans.
AB  - BACKGROUND: Based on maximisation of cardiac stroke volume (SV), peri-operative
      individualised goal-directed fluid therapy improves patient outcome. It remains,
      however, unknown how fluid therapy by this strategy relates to filling of the
      heart during supine rest as reference for the anaesthetised patient and whether
      the heart becomes distended. To answer these questions, this study related SV to
      the diastolic filling of the heart while varying central blood volume (CBV)
      between hypo- and hyper-volaemia, simulating bleeding, and fluid loading,
      respectively, when exposing healthy human subjects to head-up (HUT) and head-down
      tilt (HDT). METHODS: Twelve healthy volunteers underwent graded tilt from 20
      degrees HDT to 30 degrees HUT. The end-diastolic dimensions of the heart were
      assessed by transthoracic echocardiography with independent evaluation of SV by
      Modelflow. The CBV was monitored by thoracic electrical admittance, central
      venous oxygenation and pressure, and arterial plasma atrial natriuretic peptide.
      Also, muscle and brain oxygenation were assessed by near infrared spectroscopy
      (n=7). RESULTS: The HUT reduced the mentioned indices of CBV, the end-diastolic
      dimensions of the heart, and SV. Conversely, HDT-enhanced tissue oxygenation and
      the diastolic filling of the heart, but not SV. CONCLUSIONS: In healthy supine
      humans, the heart is provided with a volume that is sufficient to secure a
      maximal SV without distending the heart. The implication for individualised goal
      directed fluid therapy is that when a maximal SV is established for patients,
      cardiac pre-load is comparable to that of supine healthy subjects.

PMID- 18339160
TI  - Leptin and perioperative neuroendocrine stress response with two different
      anaesthetic techniques.
AB  - BACKGROUND: Stress response to surgery is modulated by several factors, including
      magnitude of the injury, pain, type of procedure and choice of anaesthesia. Our
      purpose was to compare intra- and post-operative hormonal changes during total
      intravenous anaesthesia (TIVA) using propofol and remifentanil vs. sevoflurane
      anaesthesia in a low stress level surgical model (laparoscopy). METHODS: We
      randomly allocated 18 patients undergoing laparoscopic surgery for benign ovarian
      cysts in two groups to receive either TIVA (group A=9) or sevoflurane anaesthesia
      (group B=9). Perioperative plasma levels of norepinephrine (NE), epinephrine (E),
      adrenocorticotropic hormone (ACTH), cortisol and leptin were measured. Blood
      samples were collected pre-operatively (time 0), 30 min after the beginning of
      surgery (time 1), after extubation (time 2), and 2 h (time 3) and 4 h after
      surgery (time 4). RESULTS: The comparative analysis between the groups shows
      significantly higher values of NE (P<0.001 at time 1 and P<0.01 at time 3), E
      (P<0.001 at times 1 and 2; P<0.01 at time 3 and P<0.05 at time 4), ACTH (P<0.001
      at times 1 and 2; P<0.05 at time 3) and cortisol (P<0.001 at times 1 and 2;
      P<0.01 at time 3; P<0.05 at time 4) in group B. The serum values of leptin were
      not significantly different between the two groups. CONCLUSION: The choice of
      anaesthesia does not seem to affect the leptin serum levels but influences the
      release of stress response markers: ACTH, cortisol, NE and E.

PMID- 18339161
TI  - Population pharmacokinetics of sevoflurane in conjunction with the AnaConDa:
      toward target-controlled infusion of volatiles into the breathing system.
AB  - BACKGROUND: The Anesthetic Conserving Device (AnaConDa) uncouples delivery of a
      volatile anesthetic (VA) from fresh gas flow (FGF) using a continuous infusion of
      liquid volatile into a modified heat-moisture exchanger capable of adsorbing VA
      during expiration and releasing adsorbed VA during inspiration. It combines the
      simplicity and responsiveness of high FGF with low agent expenditures. We
      performed in vitro characterization of the device before developing a population
      pharmacokinetic model for sevoflurane administration with the AnaConDa, and
      retrospectively testing its performance (internal validation). MATERIALS AND
      METHODS: Eighteen females and 20 males, aged 31-87, BMI 20-38, were included. The
      end-tidal concentrations were varied and recorded together with the VA infusion
      rates into the device, ventilation and demographic data. The concentration-time
      course of sevoflurane was described using linear differential equations, and the
      most suitable structural model and typical parameter values were identified. The
      individual pharmacokinetic parameters were obtained and tested for covariate
      relationships. Prediction errors were calculated. RESULTS: In vitro studies
      assessed the contribution of the device to the pharmacokinetic model. In vivo,
      the sevoflurane concentration-time courses on the patient side of the AnaConDa
      were adequately described with a two-compartment model. The population median
      absolute prediction error was 27% (interquartile range 13-45%). CONCLUSION: The
      predictive performance of the two-compartment model was similar to that of models
      accepted for TCI administration of intravenous anesthetics, supporting open-loop
      administration of sevoflurane with the AnaConDa. Further studies will focus on
      prospective testing and external validation of the model implemented in a target
      controlled infusion device.

PMID- 18339162
TI  - Addition of ketamine to propofol for initiation of procedural anesthesia in
      children reduces propofol consumption and preserves hemodynamic stability.
AB  - BACKGROUND: There is no ideal anesthesia protocol to perform short invasive
      procedures in pediatric oncology. The combination of propofol and ketamine may
      offer advantages over propofol alone. METHODS: In a prospective, randomized,
      double-blind study, we analyzed 63 consecutive procedures performed in 47
      oncology children. All patients received 1 mug/kg fentanyl, followed by propofol
      1 mg/kg in group P (n=33) or propofol 0.5 mg/kg and ketamine 0.5 mg/kg in group
      PK (n=30) for the initiation of anesthesia. The need for supplementation with
      propofol and/or fentanyl to maintain an adequate level of anesthesia was
      recorded. The hemodynamic and respiratory profile, recovery time and the
      occurrence of side effects were compared. RESULTS: Significantly more children
      required propofol (100% vs. 83.3%) and fentanyl (75.5% vs. 43.3%) rescue doses,
      and developed hypotension (63.6% vs. 23.4%) and bradycardia (48.5 vs. 23.4%) in
      group P compared with group PK, with a comparable incidence of respiratory
      adverse events and recovery times. However, 40% of children in group PK were
      agitated following recovery compared with 6% in group P. CONCLUSIONS: The
      combination of propofol and ketamine for invasive procedures in pediatric
      oncology resulted in reduced propofol and fentanyl consumption and preserved
      hemodynamic stability, but more children in the combination group recovered with
      agitation.

PMID- 18339163
TI  - Iatrogenic systemic air embolism treated with hyperbaric oxygen therapy.
AB  - Air embolism is a rare and potentially severe complication of surgical and
      invasive procedures. Emboli large enough to produce symptoms require immediate
      treatment because of the risk of 'gas lock' in the right side of the heart and
      subsequent circulatory failure. If air is transmitted to the arterial circulation
      through a shunt, it may cause cerebral emboli with neurological symptoms. We
      present two cases with venous air emboli and concurrent cerebral arterial emboli.
      Both patients were successfully treated with hyperbaric oxygen therapy.

PMID- 18339164
TI  - Ethics of infusing irrigating fluid.

PMID- 18339165
TI  - Complications following accidental administration of 1.5% glycine intravenously.

PMID- 18339166
TI  - Role of ketamine in 'vicarious pain'.

PMID- 18339167
TI  - Cobra perilaryngeal airway as a rescue device for failed rapid sequence
      intubation.

PMID- 18339168
TI  - Health aspects among personnel working with nitrous oxide for procedural pain
      management in children.

PMID- 18339169
TI  - Detection of inadvertent tracheal placement of nasogastric tubes.

PMID- 18339170
TI  - Severe anaphylaxis during general anaesthesia in a beta-blocked cardiac patient:
      considerations.

PMID- 18339171
TI  - Spontaneously breathing technique for opioid tolerance.

PMID- 18339172
TI  - Functional haemodynamics during intra-abdominal hypertension: what to use and
      what not use.

PMID- 18339173
TI  - Good Clinical Research Practice guidelines and PK-PD modelling without twitch
      stabilisation.

PMID- 18339175
TI  - Perioperative myocardial infarction after cesarean section in a young woman with
      hypertrophic obstructive cardiomyopathy.

PMID- 18339176
TI  - Should a compatible syringe be provided with available disposable spinal needles?

PMID- 18339177
TI  - Two-person capnography-cum-vision-guided endotracheal intubation in a case of
      laryngeal growth covering the glottic opening.

PMID- 18339178
TI  - Anesthesia for laparoscopic cholecystectomy: don't let evidence confuse you.

PMID- 18339179
TI  - Seventh International Symposium on Lysosomal Storage Diseases.

PMID- 18339180
TI  - Lysosomal storage diseases: new challenges.

PMID- 18339181
TI  - Biomarkers for lysosomal storage disorders: identification and application as
      exemplified by chitotriosidase in Gaucher disease.
AB  - A biomarker is an analyte that indicates the presence of a biological process
      linked to the clinical manifestations and outcome of a particular disease. An
      ideal biomarker provides indirect but ongoing determinations of disease activity.
      In the case of lysosomal storage disorders (LSDs), metabolites or proteins
      specifically secreted by storage cells are good candidates for biomarkers.
      Potential clinical applications of biomarkers are found in improved diagnosis,
      monitoring of disease progression and assessment of therapeutic correction. These
      applications are illustrated by reviewing the use of plasma chitotriosidase in
      the clinical management of patients with Gaucher disease, the most common LSD.
      The ongoing debate on the value of biomarkers in patient management is addressed.
      Novel analytical methods have revolutionized the identification and measurement
      of biomarkers at the protein and metabolite level. Recent developments in
      biomarker discovery by proteomics are described and the future for biomarkers of
      LSDs is discussed. CONCLUSION: Besides direct applications for biomarkers in
      patient management, biomarker searches are likely to render new insights into
      pathophysiological mechanisms and metabolic adaptations, and may provide new
      targets for therapeutic intervention.

PMID- 18339182
TI  - Metachromatic leukodystrophy: genetics, pathogenesis and therapeutic options.
AB  - Metachromatic leukodystrophy is a lysosomal storage disease caused by the
      deficiency of arylsulphatase A (ASA). This leads to storage of the membrane lipid
      sulphatide, which is abundant in myelin. A pathological hallmark of the disease
      is demyelination, causing various and ultimately lethal neurological symptoms.
      Today more than 110 mutations in the ASA gene have been identified, of which only
      three are frequent. Patients homozygous for alleles, which do not allow for the
      synthesis of functional ASA always suffer from the severe form of the disease,
      whereas alleles allowing the expression of residual enzyme activity are
      associated with the later onset juvenile or adult forms of metachromatic
      leukodystrophy. In addition, there are other as yet unknown genetic or epigenetic
      factors modifying the phenotype substantially. ASA-deficient mice have been
      generated as a model of metachromatic leukodystrophy. These mice store sulphatide
      and show progressive neurological symptoms, but do not demyelinate. This animal
      model was recently improved using a transgenic approach, which generated mice in
      which sulphatide synthesis in myelin-producing cells is enhanced. This new animal
      model reflects the pathological characteristics of the human disease. ASA
      deficient mice have been used in various therapeutic trials involving enzyme
      replacement, haematopoietic stem-cell-based gene therapy and direct injections of
      ASA-expressing viral vectors into the brain. These animal studies have paved the
      way for future clinical studies of enzyme replacement and gene therapy.
      CONCLUSION: For many years this devastating disorder was considered untreatable
      and the outlook for patients was poor. Within a comparatively short period of
      time since the ASA gene was cloned in 1989, genetic and biochemical studies and
      data generated from newly developed animal models have led to the first clinical
      trials. It is hoped that these developments will prove beneficial for patients.

PMID- 18339184
TI  - Fabry disease: beyond men.

PMID- 18339183
TI  - CNS-directed gene therapy for lysosomal storage diseases.
AB  - Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders
      usually caused by deficient activity of a single lysosomal enzyme. As most
      lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can
      affect multiple organ systems, including the central nervous system (CNS). At
      least 75% of all LSDs have a significant CNS component. Approaches such as bone
      marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively
      treat the systemic disease associated with LSDs in some patients. However, CNS
      disease remains a major challenge. Gene therapy represents a promising approach
      for the treatment of CNS disease as it has the potential to provide a permanent
      source of the deficient enzyme. Direct intracranial injection of viral gene
      transfer vectors has resulted in reduced lysosomal storage and functional
      improvement in certain small (rodent) and large (canine and feline) animal models
      of LSDs. The addition of protein transduction domains (PTDs) to the recombinant
      enzymes increased the distribution of enzyme and the extent of correction.
      Therapeutic levels of lysosomal enzymes can also be delivered to distant sites in
      the brain by anterograde and retrograde axonal transport. Finally, combining
      disparate approaches such as BMT and CNS-directed gene therapy can increase
      treatment efficacy in LSDs with severe CNS disease that are refractory to more
      conventional approaches. CONCLUSION: The development of gene transfer vectors
      that mediate persistent expression in vivo, the addition of PTDs, a better
      understanding of lysosomal enzyme trafficking and combining different therapies
      provide hope that the CNS component of LSDs can be effectively treated.

PMID- 18339185
TI  - Newborn screening for lysosomal storage disorders.
AB  - Newborn screening is a public health programme aimed at identifying treatable
      conditions in pre-symptomatic newborns to avoid premature mortality, morbidity
      and disabilities. With the advent of successful treatment options for an
      increasing number of lysosomal storage disorders (LSDs), such as enzyme
      replacement or bone marrow transplantation, inclusion of these disorders into
      newborn screening programmes seems reasonable. However, the success of these
      programmes depends on the availability of testing methods that are suitable for
      population screening, have high sensitivity and a low false-positive rate. In
      recent years, two methods have been proposed for newborn screening of LSDs, which
      enable assessment of more than one LSD from a single blood spot sample. One
      applies tandem mass spectrometry, the other microbead array technology. Now,
      prospective studies are needed to determine the most effective approach to
      newborn screening that will identify those patients who require treatment.
      CONCLUSION: With the advent of high-throughput assays for the detection of LSDs,
      newborn screening for these disorders may soon become a reality. However, careful
      prospective studies are required to optimize this process before it is used on a
      larger scale.

PMID- 18339186
TI  - Fabry disease during childhood: clinical manifestations and treatment with
      agalsidase alfa.
AB  - Fabry disease is a rare X-linked disorder that leads to widespread and
      progressive disease manifestations, with patients at risk of premature mortality
      as a result of renal, cardiovascular or cerebrovascular complications. In recent
      years there has been a growing awareness that the first signs and symptoms of
      Fabry disease may begin during childhood. Studies show that clinical
      manifestations such as pain, hypohidrosis, gastrointestinal disturbances,
      angiokeratomas, cornea verticillata and acroparaesthesiae may be common in
      childhood and that such manifestations may become apparent during the first few
      years of life. Despite the early onset of these signs and symptoms, however,
      diagnosis is often delayed. Interest is now focused on whether enzyme replacement
      therapy can slow or prevent the onset of these disease manifestations.
      Preliminary data from two studies suggest that treatment with agalsidase alfa is
      well tolerated in children and that it may have beneficial clinical effects;
      however, further research is needed to determine whether enzyme replacement
      therapy can prevent the development of disease manifestations. CONCLUSION: The
      manifestations of Fabry disease first become apparent during childhood. It is
      well known that disease-associated manifestations are progressive; however, it
      has yet to be determined whether specific treatment with enzyme replacement
      therapy can prevent the development of the associated severe and life-threatening
      complications.

PMID- 18339187
TI  - Early therapeutic intervention in females with Fabry disease?
AB  - Anderson-Fabry disease is an X-linked lysosomal storage disorder resulting from
      deficiency of alpha-galactosidase A. The subsequent accumulation of
      globotriaosylceramide (Gb3) in cells and tissues of the body has multisystemic
      effects and significantly impacts upon quality of life and survival of
      individuals with this condition. In general, Anderson-Fabry disease is more
      severe in male patients; however, despite X-linkage, females may develop severe
      signs and symptoms of the disease, although there is considerable phenotypic
      heterogeneity, which correlates most closely with age. Histological analyses of
      biopsies have shown evidence of Gb3 storage in the kidney and heart in female
      patients. Gb3 levels are also elevated in the urine of females, although plasma
      Gb3 levels are not reliably elevated. The efficacy of enzyme replacement therapy
      (ERT) with recombinant human alpha-galactosidase A has been demonstrated in
      females in a clinical trial and in observational studies, including those using
      data from outcome surveys. Benefits include a reduction in left ventricular mass,
      stabilization of renal function and improvements in pain and quality of life.
      CONCLUSION: If early intervention with ERT in females is to be advocated, it is
      necessary to demonstrate not only that females with Anderson-Fabry disease have
      clinical and biochemical features of alpha-galactosidase A deficiency and respond
      to ERT, but also that early intervention prevents the onset of the later
      manifestations of the disorder. Any strategy for early therapy should also
      balance future advantages against any impact on quality of life.

PMID- 18339188
TI  - Apoptotic abnormalities in differential gene expression in peripheral blood
      mononuclear cells from children with Fabry disease.
AB  - AIM: This study was designed to examine the effect of enzyme replacement therapy
      (ERT) on differential gene expression in peripheral blood mononuclear cells
      (PBMCs) of children with Fabry disease who had not previously been exposed to
      ERT. METHODS: Thirteen children with Fabry disease (age range, 6.5-17.0 years)
      were studied as part of a 6-month, open-label study of ERT with agalsidase alfa.
      Paired blood samples were taken at the start of the study and after 6 months of
      ERT. Further blood samples were also taken from 16 age-matched control subjects.
      PBMCs were isolated and, following RNA extraction, differential gene expression
      analysis was performed using the Human Genome U133 Plus 2.0 microarray. RESULTS:
      Twenty-one genes were determined to be differentially expressed in PBMCs of ERT
      naive children with Fabry disease compared with healthy controls; neuronal
      apoptosis inhibitory protein ranked as the most significantly differentially
      expressed gene. Comparison of gene expression in children with Fabry disease
      prior to and after ERT showed that two genes were significantly differentially
      expressed (p < or = 0.05) following treatment; the expressed sequence tag (probe
      set ID, 243259_at) was downregulated, while expression of apoptosis-inducing
      factor was increased, possibly as an antioxidant counter-regulatory response.
      CONCLUSION: This study identifies a number of genes that are differentially
      expressed in a small cohort of children with Fabry disease relative to healthy
      controls. These genes may relate to the underlying biological abnormalities in
      Fabry disease.

PMID- 18339189
TI  - Hunter syndrome: to treat or not to treat.

PMID- 18339190
TI  - Diagnosis and management of respiratory involvement in Hunter syndrome.
AB  - Respiratory problems are frequently encountered by patients with Hunter syndrome
      and contribute to the premature mortality seen in individuals with the disease.
      Progressive deposition of glycosaminoglycans in the soft tissue of the throat and
      trachea is thought to be responsible for the airway dysfunction and obstruction,
      which characterize the syndrome. Other physical characteristics, including
      abnormalities in the shape and structure of the ribs, abdominal organ
      enlargement, short neck and immobile jaw, further contribute to the respiratory
      problems. New measurement systems specifically tailored to paediatric patients
      now allow clinicians to follow the progressive deterioration of lung function,
      which was previously challenging in this population. Sleep apnoea is another
      common feature of Hunter syndrome, which can lead to a reduction in oxygen
      saturation of the blood and severely disrupts sleep. In our clinic, continuous
      positive airway pressure (CPAP), in which inspired air at elevated pressure is
      delivered through a specially designed mask, has proved to be effective for
      reducing sleep apnoea in patients with Hunter syndrome. As a consequence of the
      anatomical and pathological changes in the upper airways of patients with Hunter
      syndrome, general anaesthesia - especially intubation - is a difficult and
      potentially high-risk procedure. Consequently, such procedures should be
      performed by an anaesthetist - ideally accompanied by a paediatric
      pneumologist/intensivist - with experience in managing patients with Hunter
      syndrome. CONCLUSION: Respiratory abnormalities are a major contributor to the
      premature mortality seen in Hunter syndrome. Treatment of these respiratory
      problems requires the careful attention of clinicians skilled in the recognition,
      diagnosis, management and treatment of Hunter syndrome.

PMID- 18339191
TI  - Magnetic resonance imaging findings in Hunter syndrome.
AB  - Hunter syndrome is a rare genetic lysosomal storage disease that is caused by a
      deficiency, or absence, of iduronate-2-sulphatase, an enzyme needed to break down
      specific glycosaminoglycans (GAGs). As a result, GAGs build up in various tissues
      throughout the body leading to adverse neurological and non-neurological effects.
      This literature review focuses on the neurological findings. Although few
      magnetic resonance imaging studies have been conducted, those done have shown
      that patients with Hunter syndrome generally exhibit brain atrophy, enlarged
      periventricular spaces and ventriculomegaly. Similar findings have been reported
      in other mucopolysaccharide disorders. Enzyme replacement therapy is a novel
      treatment which has had success in treating peripheral disease in mice and
      humans. CONCLUSION: Future studies should focus on how structural and chemical
      signatures in the brain of Hunter patients are altered before and after enzyme
      replacement therapy, and how those alterations correlate with clinical outcome.

PMID- 18339192
TI  - Methods for assessing neurodevelopment in lysosomal storage diseases and related
      disorders: a multidisciplinary perspective.
AB  - Lysosomal storage diseases and related disorders (LSRDs) are a heterogeneous
      group of rare diseases caused by genetic mutations that result in deficiencies of
      specific lysosomal enzymes. Some of these enzymes are necessary for normal
      development of the central and peripheral nervous systems. Because of the
      heterogeneity in clinical presentation and complexity of these disorders,
      evaluation of disease progression poses unique challenges. In recent years,
      recombinant enzyme replacement therapy and haematopoietic stem cell
      transplantation have been developed to treat some of these diseases. With the
      development of specific therapies and screening programmes, there is a need to
      systematically follow the natural course and effects of treatment in these
      disorders with standardized and validated tools. This review describes the
      limitations of currently available neurobehavioural tools in longitudinally
      tracking disease outcomes in patients with neurodegenerative LSRDs. A
      multidisciplinary team reviewed over 750 evaluations in 274 patients. These
      patients were found to have neurological, sensory and somatic problems that
      considerably influence the results of neurobehavioural testing. CONCLUSION:
      Treatment effects in patients with neurodegenerative LSRDs are best evaluated by
      repeated measures and longitudinal analysis of each domain of function.

PMID- 18339193
TI  - Enzyme replacement therapy with idursulfase in patients with
      mucopolysaccharidosis type II.
AB  - Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is a rare X-linked
      recessive disease caused by deficiency of the lysosomal enzyme iduronate-2
      sulphatase. This leads to the progressive accumulation of glycosaminoglycans in
      tissues throughout the body. As a result, patients may suffer from severe airway
      obstruction, skeletal deformities, cardiomyopathy and, in severely affected
      patients, there may be progressive neurological decline. Despite the early onset
      of signs and symptoms, diagnosis is often delayed. Until recently, treatment for
      MPS II has been largely palliative; however, enzyme replacement therapy with
      recombinant iduronate-2-sulphatase, which is produced in a human cell line and
      targets the underlying cause of the disease, has now been approved. CONCLUSION:
      This short review provides an overview of the natural history of MPS II and
      current experience of enzyme replacement therapy with idursulfase.

PMID- 18339194
TI  - Gaucher disease: improving management.

PMID- 18339195
TI  - Gaucher disease: unmet treatment needs.
AB  - Gaucher disease is a multisystemic metabolic disorder arising from a deficiency
      of lysosomal glucocerebrosidase. The predominant clinical manifestations of the
      disease are hepatosplenomegaly, peripheral blood cytopenias and skeletal disease.
      Treatment with enzyme replacement therapy (ERT) and substrate reduction therapy
      (SRT) has been shown to be effective in improving organ volume, anaemia,
      thrombocytopenia, bone markers and biomarkers in patients with Gaucher disease.
      However, some patient needs remain unmet because of the limited availability of
      treatment, the inaccessibility of certain disease sites and emerging disease
      manifestations. An increase in haematological, lymphoreticular and immune system
      malignancies has been observed in patients with Gaucher disease, but mechanisms
      underlying the development of these are not fully understood. Mild neurological
      manifestations may also affect patients with type 1 Gaucher disease, but
      treatment with ERT or SRT does not improve neurological function. Potential new
      treatments for Gaucher disease include small molecules, which may penetrate
      tissues that are not accessible by ERT. CONCLUSION: ERT currently remains the
      most effective treatment for Gaucher disease. New treatments are emerging, but
      deficiencies in understanding basic pathophysiological mechanisms hinder
      progress.

PMID- 18339196
TI  - Substrate reduction therapy.
AB  - The therapeutic options for lysosomal storage diseases (LSDs) have expanded
      greatly over the past decade, although for many disorders there is still no
      effective treatment. Given that the majority of LSDs involve pathological changes
      in both the brain and peripheral tissues, effective treatment of central nervous
      system (CNS) and peripheral manifestations still remains a considerable technical
      challenge. Type 1 Gaucher disease has two approved treatment modalities - enzyme
      replacement therapy (ERT) and substrate reduction therapy (SRT) - which have
      unique, independent and potentially complementary mechanisms of action. The
      availability of these two therapies has greatly increased the options for the
      effective clinical management of type 1 Gaucher disease. ERT involves the
      intravenous administration of fully functional enzyme that is taken up by cells
      and delivered to the lysosome, where it can compensate for the underlying enzyme
      deficiency. SRT uses an orally available, small molecule drug that inhibits the
      first committed step in glycosphingolipid biosynthesis. The aim is to reduce the
      rate of biosynthesis of glycosphingolipids to offset the catabolic defect,
      restoring the balance between the rate of biosynthesis and the rate of
      catabolism. SRT also has the potential to treat LSDs with CNS pathology, as the
      drug in clinical use (miglustat, Zavesca; Actelion Pharmaceuticals Ltd,
      Allschwil, Switzerland) crosses the blood-brain barrier. In this review, the
      current status of SRT for the treatment of Gaucher disease and other LSDs will be
      discussed, based upon preclinical and clinical studies. CONCLUSION: SRT is an
      oral alternative treatment option for patients with type 1 Gaucher disease
      unwilling or unable to receive ERT. With the recent reports of clinical
      improvement/stabilization of CNS manifestations following SRT in patients with
      Niemann-Pick disease type C, miglustat may also have a role to play in the
      management of patients with glycosphingolipid storage in the brain. Furthermore,
      as SRT synergises with other therapeutic modalities, it may also prove to be a
      key component of combination therapies in the future.

PMID- 18339197
TI  - Proceedings of the Seventh International Symposium on Lysosomal Storage Diseases.
      April 2007. Rome, Italy.

PMID- 18339198
TI  - Evaluation of the new advanced 15-loci MIRU-VNTR genotyping tool in Mycobacterium
      tuberculosis molecular epidemiology studies.
AB  - BACKGROUND: During the last few years, PCR-based methods have been developed to
      simplify and reduce the time required for genotyping Mycobacterium tuberculosis
      (MTB) by standard approaches based on IS6110-Restriction Fragment Length
      Polymorphism (RFLP). Of these, MIRU-12-VNTR (Mycobacterial interspersed
      repetitive units- variable number of tandem repeats) (MIRU-12) has been
      considered a good alternative. Nevertheless, some limitations and discrepancies
      with RFLP, which are minimized if the technique is complemented with
      spoligotyping, have been found. Recently, a new version of MIRU-VNTR targeting 15
      loci (MIRU-15) has been proposed to improve the MIRU-12 format. RESULTS: We
      evaluated the new MIRU-15 tool in two different samples. First, we analyzed the
      same convenience sample that had been used to evaluate MIRU-12 in a previous
      study, and the new 15-loci version offered higher discriminatory power (Hunter
      Gaston discriminatory index [HGDI]: 0.995 vs 0.978; 34.4% of clustered cases vs
      57.5%) and better correlation (full or high correlation with RFLP for 82% of the
      clusters vs 47%). Second, we evaluated MIRU-15 on a population-based sample and,
      once again, good correlation with the RFLP clustering data was observed (for 83%
      of the RFLP clusters). To understand the meaning of the discrepancies still found
      between MIRU-15 and RFLP, we analyzed the epidemiological data for the clustered
      patients. In most cases, splitting of RFLP-clustered patients by MIRU-15 occurred
      for those without epidemiological links, and RFLP-clustered patients with
      epidemiological links were also clustered by MIRU-15, suggesting a good
      epidemiological background for clustering defined by MIRU-15. CONCLUSION: The
      data obtained by MIRU-15 suggest that the new design is very efficient at
      assigning clusters confirmed by epidemiological data. If we add this to the speed
      with which it provides results, MIRU-15 could be considered a suitable tool for
      real-time genotyping.

PMID- 18339199
TI  - Good functional recovery following intervention for delayed suprachoroidal
      haemorrhage post bleb needling: a case report.
AB  - INTRODUCTION: Bleb needling is a recognised procedure in the management of
      patients with failing trabeculectomies. Suprachoroidal haemorrhage can occur as
      an unusual complication. We report a pseudophakic man who had early surgical
      intervention for this complication. This intervention may have contributed to the
      good recovery of his visual acuity and the minimum changes to his visual fields.
      CASE PRESENTATION: A 79-year-old pseudophakic man with chronic open angle
      glaucoma presented with further deterioration of his right visual field despite
      maximum medical therapy and a previous trabeculectomy. The right visual acuity
      was 6/9 with an intraocular pressure (IOP) of 16 mmHg. Bleb needling with 5
      fluouracil was performed in a standard manner. His postoperative IOP was 6 mmHg.
      Thirty-six hours later the visual acuity was reduced to hand movements and two
      large choroidal detachments where observed clinically, which progressed to
      suprachoroidal haemorrhages. Five days after the initial needling, the patient
      had complex surgery involving anterior chamber reformation, a bleb compression
      suture and drainage of the haemorrhagic suprachoroidal detachments. Subsequently,
      the patient had a right vitrectomy with endolaser following a vitreous
      haemorrhage. The final visual acuity was 6/9 with an intraocular pressure of 8
      mmHg on travoprost and brinzolamide. The final visual field showed little change
      when compared with the pre-suprachoroidal haemorrhage visual field. CONCLUSION:
      It is important to consider the possibility of delayed suprachoroidal haemorrhage
      as a complication in bleb needling, and early surgical intervention may be
      beneficial.

PMID- 18339200
TI  - Miliary tuberculosis with no pulmonary involvement in myelodysplastic syndromes:
      a curable, yet rarely diagnosed, disease: case report and review of the
      literature.
AB  - BACKGROUND: Although tuberculosis is not uncommon among patients with
      myelodysplastic syndrome (MDS), only a few reports of such patients suffering
      from miliary tuberculosis (MT) exist. MT often presents as a fever of unknown
      origin and it is a curable disease, yet fatal if left untreated. CASE
      PRESENTATION: We report a case of MT with no clinical or laboratory indications
      of pulmonary involvement in a patient with MDS, and review the relevant
      literature. Mycobacterium tuberculosis was isolated from the liquid culture of a
      bone marrow aspirate. CONCLUSION: Even if the initial diagnostic investigation
      for a fever of obscure etiology is negative, MT should not be excluded from the
      differential diagnosis list. Since it is a curable disease, persistent and
      vigorous diagnostic efforts are warranted. In suspected cases, mycobacterial
      blood cultures should be collected as soon as possible after hospital admission
      and early bone marrow aspirate with mycobacterial cultures is advocated.

PMID- 18339201
TI  - Sleep patterns and habits in high school students in Iran.
AB  - BACKGROUND: Sleep patterns and habits in high school students in Iran have not
      been well studied to date. This paper aims to re-address this balance and analyse
      sleep patterns and habits in Iranian children of high school age. METHODS: The
      subjects were 1,420 high school students randomly selected by stratified cluster
      sampling. This was a self-report study using a questionnaire which included items
      about usual sleep/wake behaviours over the previous month, such as sleep
      schedule, falling asleep in class, difficulty falling asleep, tiredness or
      sleepiness during the day, difficulty getting up in the morning, nightmares, and
      taking sleeping pills. RESULTS: The mean duration of night sleep was 7.7 h, with
      no difference between girls, boys, and school year (grade). The mean time of
      waking in the morning was not different between genders. About 9.9% of the girls
      and 4.6% of the boys perceived their quality of sleep as being bad, and 58% of
      them reported sleepiness during the day. About 4.2% of the subjects had used
      medication to enhance sleep. The time of going to bed was associated with grade
      level and gender. Sleep latency was not associated with gender and grade level, l
      and 1.4% experienced bruxism more than four times a week. CONCLUSION: Our results
      are in contrast with that of previous studies that concluded sleep duration is
      shorter in Asia than in Europe, that boys woke-up significantly later than girls,
      and that the frequency of sleep latency category was associated with gender and
      grade level. The magnitude of the daytime sleepiness, daytime sleepiness during
      classes, sleep latency, and incidences of waking up at night represent major
      public health concerns for Iran.

PMID- 18339202
TI  - Metabolic responses to pyruvate kinase deletion in lysine producing
      Corynebacterium glutamicum.
AB  - BACKGROUND: Pyruvate kinase is an important element in flux control of the
      intermediate metabolism. It catalyzes the irreversible conversion of
      phosphoenolpyruvate into pyruvate and is under allosteric control. In
      Corynebacterium glutamicum, this enzyme was regarded as promising target for
      improved production of lysine, one of the major amino acids in animal nutrition.
      In pyruvate kinase deficient strains the required equimolar ratio of the two
      lysine precursors oxaloacetate and pyruvate can be achieved through concerted
      action of the phosphotransferase system (PTS) and phosphoenolpyruvate carboxylase
      (PEPC), whereby a reduced amount of carbon may be lost as CO2 due to reduced flux
      into the tricarboxylic acid (TCA) cycle. In previous studies, deletion of
      pyruvate kinase in lysine-producing C. glutamicum, however, did not yield a clear
      picture and the exact metabolic consequences are not fully understood. RESULTS:
      In this work, deletion of the pyk gene, encoding pyruvate kinase, was carried out
      in the lysine-producing strain C. glutamicum lysCfbr, expressing a feedback
      resistant aspartokinase, to investigate the cellular response to deletion of this
      central glycolytic enzyme. Pyk deletion was achieved by allelic replacement,
      verified by PCR analysis and the lack of in vitro enzyme activity. The deletion
      mutant showed an overall growth behavior (specific growth rate, glucose uptake
      rate, biomass yield) which was very similar to that of the parent strain, but
      differed in slightly reduced lysine formation, increased formation of the
      overflow metabolites dihydroxyacetone and glycerol and in metabolic fluxes around
      the pyruvate node. The latter involved a flux shift from pyruvate carboxylase
      (PC) to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle.
      This created a metabolic by-pass from PEP to pyruvate via malic enzyme
      demonstrating its contribution to metabolic flexibility of C. glutamicum on
      glucose. CONCLUSION: The metabolic flux analysis performed illustrates the high
      flexibility of the metabolic network of C. glutamicum to compensate for external
      perturbation. The organism could almost maintain its growth and production
      performance through a local redirection of the metabolic flux, thereby fulfilling
      all anabolic and catabolic needs. The formation of the undesired overflow
      metabolites dihydroxyacetone and glycerol, in the deletion mutant, however,
      indicates a limiting capacity of the metabolism down-stream of their common
      precursor glyceraldehyde 3-phosphate and opens possibilities for further strain
      engineering.

PMID- 18339203
TI  - Pseudosarcomatous myofibroblastic lesion of the urinary bladder: a rare entity
      posing a diagnostic challenge and therapeutic dilemma.
AB  - BACKGROUND: Pseudosarcomatous myofibroblastic lesions of the urinary bladder are
      relatively rare entities of an uncertain pathogenesis and benign indolent nature.
      CASE PRESENTATION: We present an extremely rare case of an ALK-1-positive
      pseudosarcomatous myofibroblastic lesion of the urinary bladder, which was
      initially misinterpreted as a low-grade leiomyosarcoma of myxoid subtype on
      histologic examination owing to prominent atypia, high mitotic activity, abnormal
      mitotic figures and infiltration of the bladder wall. Although the histologic
      features were suggestive of a sarcoma, the correct diagnosis was finally
      established and radical surgical treatment was subsequently avoided. The patient
      is currently free of disease without any evidence of tumor recurrence or
      metastasis at 3 years post-operatively. CONCLUSION: The key differentiating point
      rests in distinguishing the aforementioned mass forming lesion from the myxoid
      subtype of low-grade leiomyosarcoma in order to avoid unnecessary radical
      therapy.

PMID- 18339204
TI  - Association between the FTO rs9939609 polymorphism and the metabolic syndrome in
      a non-Caucasian multi-ethnic sample.
AB  - BACKGROUND: The rs9939609 T>A single-nucleotide polymorphism (SNP) in the FTO
      gene has previously been found to be associated with obesity in European
      Caucasian samples. The objective of this study is to examine whether this
      association extends to metabolic syndrome (MetS) and applies in non-Caucasian
      samples. METHODS: The FTO rs9939609 SNP was genotyped in 2121 subjects from four
      different non-Caucasian geographical ancestries. Subjects were classified for the
      presence or absence of MetS according to the International Diabetes Federation
      (IDF) and National Cholesterol Education Program Adult Treatment Panel (NCEP ATP)
      III definitions. RESULTS: Carriers of > or = 1 copy of the rs9939609 A allele
      were significantly more likely to have IDF-defined MetS (35.8%) than non-carriers
      (31.2%), corresponding to a carrier odds ratio (OR) of 1.23 (95% confidence
      interval [CI] 1.01 to 1.50), with a similar trend for the NCEP ATP III-defined
      MetS. Subgroup analysis showed that the association was particularly strong in
      men. The association was related to a higher proportion of rs9939609 A allele
      carriers meeting the waist circumference criterion; a higher proportion also met
      the HDL cholesterol criterion compared with wild-type homozygotes. CONCLUSION:
      Thus, the FTO rs9939609 SNP was associated with an increased risk for MetS in
      this multi-ethnic sample, confirming that the association extends to non
      Caucasian population samples.

PMID- 18339205
TI  - Breast size, bra fit and thoracic pain in young women: a correlational study.
AB  - INTRODUCTION: A single sample study was undertaken to determine the strength and
      direction of correlations between: a) breast size and thoracic spine or posterior
      chest wall pain; b) bra fit and thoracic spine or posterior chest wall pain and;
      c) breast size and bra fit, in thirty nulliparous women (18-26 years), with
      thoracic spine or posterior chest wall pain, who wore bras during daytime.
      MEASURES: Pain (Short Form McGill Pain Questionnaire), bra size (Triumph
      International), bra fit (Triumph International). RESULTS: Most (80%) women wore
      incorrectly sized bras: 70% wore bras that were too small, 10% wore bras that
      were too large. Breast size was negatively correlated with both bra size (r = 
      0.78) and bra fit (r = -0.50). These results together indicate that large
      breasted women were particularly likely to be wearing incorrectly sized and
      fitted bras. Negligible relationships were found between pain and bra fit, and
      breast size and pain. Menstrual cycle stage was moderately positively correlated
      with bra fit (r = 0.32). CONCLUSION: In young, nulliparous women, thoracic pain
      appears unrelated to breast size. Bra fit is moderately related to stage of
      menstrual cycle suggesting that this research may be somewhat confounded by
      hormonal changes or reproductive stage. Further research is needed to clarify
      whether there is a relationship between breast size or bra fit and thoracic pain
      in women during times of hormonal change.

PMID- 18339206
TI  - Turning up the volume on mutational pressure: is more of a good thing always
      better? (A case study of HIV-1 Vif and APOBEC3).
AB  - APOBEC3G and APOBEC3F are human cytidine deaminases that serve as innate
      antiviral defense mechanisms primarily by introducing C-to-U changes in the minus
      strand DNA of retroviruses during replication (resulting in G-to-A mutations in
      the genomic sense strand sequence). The HIV-1 Vif protein counteracts this
      defense by promoting the proteolytic degradation of APOBEC3G and APOBEC3F in the
      host cell. In the absence of Vif expression, APOBEC3 is incorporated into HIV-1
      virions and the viral genome undergoes extensive G-to-A mutation, or
      "hypermutation", typically rendering it non-viable within a single replicative
      cycle. Consequently, Vif is emerging as an attractive target for pharmacological
      intervention and therapeutic vaccination. Although a highly effective Vif
      inhibitor may result in mutational meltdown of the viral quasispecies, a
      partially effective Vif inhibitor may accelerate the evolution of drug resistance
      and immune escape due to the codon structure and recombinogenic nature of HIV-1.
      This hypothesis rests on two principal assumptions which are supported by
      experimental evidence: a) there is a dose response between intracellular APOBEC
      concentration and degree of viral hypermutation, and, b) HIV-1 can tolerate an
      elevated mutation rate, and a true error or extinction threshold is as yet
      undetermined. Rigorous testing of this hypothesis will have timely and critical
      implications for the therapeutic management of HIV/AIDS, and delve into the
      complexities underlying the induction of lethal mutagenesis in a viral pathogen.

PMID- 18339207
TI  - Vasopressin and epinephrine in the treatment of cardiac arrest: an experimental
      study.
AB  - BACKGROUND: Epinephrine remains the drug of choice for cardiopulmonary
      resuscitation. The aim of the present study is to assess whether the combination
      of vasopressin and epinephrine, given their different mechanisms of action,
      provides better results than epinephrine alone in cardiopulmonary resuscitation.
      METHODS: Ventricular fibrillation was induced in 22 Landrace/Large-White piglets,
      which were left untreated for 8 minutes before attempted resuscitation with
      precordial compression, mechanical ventilation and electrical defibrillation.
      Animals were randomized into 2 groups during cardiopulmonary resuscitation: 11
      animals who received saline as placebo (20 ml dilution, bolus) + epinephrine
      (0.02 mg/kg) (Epi group); and 11 animals who received vasopressin (0.4 IU/kg/20
      ml dilution, bolus) + epinephrine (0.02 mg/kg) (Vaso-Epi group). Electrical
      defibrillation was attempted after 10 minutes of ventricular fibrillation.
      RESULTS: Ten of 11 animals in the Vaso-Epi group restored spontaneous circulation
      in comparison to only 4 of 11 in the Epi group (p = 0.02). Aortic diastolic
      pressure, as well as, coronary perfusion pressure were significantly increased (p
      < 0.05) during cardiopulmonary resuscitation in the Vaso-Epi group. CONCLUSION:
      The administration of vasopressin in combination with epinephrine during
      cardiopulmonary resuscitation results in a drastic improvement in the hemodynamic
      parameters necessary for the return of spontaneous circulation.

PMID- 18339208
TI  - Reduction of human chorionic gonadotropin beta subunit expression by modified U1
      snRNA caused apoptosis in cervical cancer cells.
AB  - BACKGROUND: Secretion of human chorionic gonadotropin, especially its beta
      subunit by malignant trophoblastic tumors and varieties of tumors of different
      origin is now well documented; however the role of hCG in tumorogenesis is still
      unknown. RESULTS: This study documents the molecular presence of human chorionic
      gonadotropin beta subunit in uterine cervix cancer tissues and investigates a
      novel technique to reduce hCGbeta levels based on expression of a modified U1
      snRNA as a method to study the hormone's role in biology of human cervical cancer
      cells cultured in vitro. The property of U1 snRNA to block the accumulation of
      specific RNA transcript when it binds to its donor sequence within the 3'
      terminal exon was used. The first 10 nucleotides of the human U1 snRNA gene,
      which normally binds to the 5'ss in pre-mRNA were replaced by a sequence
      complementary to a 10-nt segment in the terminal exon of the hCGbeta mRNA. Three
      different 5' end-mutated U1 snRNA expression plasmids were tested, each targeting
      a different sequence in the hCGbeta mRNA, and we found each one blocked the
      expression of hCGbeta in HeLa cells, a cervix carcinoma cell line, as shown by
      immunohistochemistry and qRT-PCR. Reduction of hCGbeta levels resulted in a
      significantly increased apoptosis rate with almost 90% of cells transfected with
      modified anti-hCGbeta U1 snRNAs showing morphological changes characteristic of
      the apoptotic process. CONCLUSION: These data suggest that human chorionic
      gonadotropin beta subunit may act as a tumor growth-stimulating factor.

PMID- 18339209
TI  - Kinetic analysis of cardiac troponin I release is no more accurate than a single
      24-h measurement in predicting in-hospital outcome after cardiac surgery.
AB  - BACKGROUND AND OBJECTIVE: A single cardiac troponin I (cTnI) 24-h measurement is
      an independent predictor of short- and long-term adverse outcome after coronary
      surgery. We compared a single cTnI 24-h measurement and kinetic analysis of cTnI
      release in predicting in-hospital outcome in unselected cardiac surgery patients.
      METHODS: Consecutive patients (n = 184) undergoing cardiac surgery with
      cardiopulmonary bypass were included and divided into two groups according to the
      time course of postoperative peak serum cTnI (6 or 24 h after surgery). Serial
      measurements of cTnI were performed the day before surgery, at the end of surgery
      and 6, 24 and 120 h after surgery in all patients. The total amount of cTnI
      released (integrated area under the curve), postoperative major adverse cardiac
      events (ventricular arrhythmias, myocardial infarction and congestive heart
      failure) and in-hospital death were recorded. Data are expressed as median (95%
      CI). RESULTS: In all, 152 (83%) patients had an early peak cTnI (6 h after
      surgery) and 32 (17%) patients had a late peak cTnI (24 h after surgery). The
      integrated area under the curve differed between both groups: 159 (142-178) vs.
      321 (255-590), respectively, P < 0.001. Major adverse cardiac events and/or death
      (22 vs. 9%, P = 0.04) was greater in patients with a late peak cTnI. The
      integrated area under the curve and the peak value of cTnI were no more accurate
      than a single 24-h measurement in predicting the occurrence of major adverse
      cardiac events and/or death. CONCLUSIONS: Kinetic analysis of cTnI release was no
      more accurate than a single 24-h measurement in predicting in-hospital poor
      outcome.

PMID- 18339210
TI  - The use of cuffed tracheal tubes for paediatric tracheal intubation, a survey of
      specialist practice in the United Kingdom.
AB  - BACKGROUND AND OBJECTIVE: For more than 50 yr, uncuffed tracheal tubes have been
      the gold standard for intubation in children under the age of 8 yr. However,
      recently there has been interest in the use of cuffed tubes in paediatric
      practice. This survey aimed to benchmark UK practice with regard to tracheal
      intubation within specialist paediatric centres, exploring current cuffed
      tracheal tube use in children. METHODS: A questionnaire was e-mailed to the
      paediatric intensive care unit and anaesthetic department clinical leads in all
      UK specialist paediatric hospitals with a paediatric intensive care unit (n =
      30). Information was requested on the use of tracheal tubes across all paediatric
      age groups, as well as the reasons for non-use and the incidence of complications
      attributed to cuffed tubes. RESULTS: A total of 20 paediatric intensive care unit
      and 15 anaesthetic questionnaires were returned, equating to a response rate of
      67% and 50%, respectively. Only 5% of the paediatric intensive care unit and 7%
      of the anaesthetic respondents routinely use a cuffed tube in children under the
      age of 8 yr. The commonest reason cited in both groups for non-cuff use was that
      there is minimal benefit to be gained over using an uncuffed tracheal tube. The
      most frequent specific indication for use of a cuffed tube was a reduced lung
      compliance (60% respondents both groups). In all, 45% of the paediatric intensive
      care unit respondents and 100% of the anaesthetists reported that they did not
      routinely monitor the intracuff pressure when using a cuffed tube. The incidence
      of observed complications attributed to the use of cuffed tubes was far higher
      amongst paediatric intensive care unit consultants (65% vs. 7% anaesthetists);
      however, the majority in both groups stated that such complications were no more
      common than when using an uncuffed tube (60% paediatric intensive care unit and
      53% anaesthetists). CONCLUSION: Cuffed tracheal tubes are rarely routinely used
      in children, particularly in the under 8 yr age group, in specialist paediatric
      centres in the UK. When used, it is predominantly for a specific indication, and
      the monitoring of intracuff pressure is not routine. Current expert consensus is
      that complications are equally as common when using a cuffed as an uncuffed tube.

PMID- 18339211
TI  - Case/problem-based learning discussion for teaching ethics to anaesthesiology
      residents.

PMID- 18339212
TI  - HES 130/0.4 (Voluven) or human albumin in children younger than 2 yr undergoing
      non-cardiac surgery. A prospective, randomized, open label, multicentre trial.
AB  - BACKGROUND AND OBJECTIVE: For perioperative volume therapy in infants and young
      children, human albumin has frequently been the colloid of choice. Recently, HES
      130/0.4 (6% hydroxyethyl starch, Voluven; Fresenius Kabi, Bad Homburg, Germany)
      was developed, which demonstrated improved pharmacokinetics and a favourable
      safety profile in adults compared with hydroxyethyl starch products with a less
      rapid metabolization. METHODS: Our prospective, controlled, randomized, open,
      multicentre pilot study was designed to obtain data on the effects of HES 130/0.4
      compared with human albumin 5% with regard to haemodynamics in children <2 yr
      scheduled for elective non-cardiac surgery. RESULTS: A total of 81 patients were
      treated. Comparable amounts of both study solutions (16.0 mL kg(-1) hydroxyethyl
      starch 130/0.4 vs. 16.9 mL kg(-1) human albumin 5%) as well as add-on
      crystalloids were used until 4-6 h postoperatively. No differences were detected
      between the two treatment groups regarding perioperative stabilization of
      haemodynamics, coagulation parameters, blood gas analyses or other laboratory
      values. Blood loss was 96 +/-143 mL for hydroxyethyl starch and 145+/- 290 mL for
      human albumin (P > 0.05). There were no relevant differences in the amount of red
      blood cells, fresh frozen plasma or platelet concentrates in both treatment
      groups. Median length of ICU stay was 3.5 days (range 1-57 days, mean +/- SD 7.6
      +/- 11.5 days) in the hydroxyethyl starch group and 6.0 days (range 1-71 days;
      mean +/- SD 9.1 +/- 14.2 days) in the human albumin group. There was no
      difference for hospital stay (median: 12 days for both groups). CONCLUSIONS: Both
      HES 130/0.4 and human albumin 5% were effective for haemodynamic stabilization in
      non-cardiac surgery of young infants with no adverse impact on coagulation or
      other safety parameters in our study population.

PMID- 18339213
TI  - Fibrinolysis or hypercoagulation during radical prostatectomy? An evaluation of
      thrombelastographic parameters and standard laboratory tests.
AB  - BACKGROUND AND OBJECTIVES: Radical prostatectomy is at high risk for
      intraoperative and postoperative bleeding due to surgical trauma, release of
      urokinase and tissue type plasminogen activator. We conducted this prospective,
      observational multi-centre study to assess the degree of systemic fibrinolysis or
      hypercoagulation in the perioperative period. We studied serial changes in
      standard laboratory values and in thrombelastographic (TEG; Haemoscope
      Corporation, Skokie, IL, USA) parameters including lysis at 30 and 60 min (LY-30,
      LY-60), alpha-angle (alpha) and maximum amplitude. METHODS: In all, 49 patients
      undergoing radical retropubic prostatectomy in five Italian University Hospitals
      were included. Blood samples were taken before surgery (T1), at the removal of
      the prostate (T2), 4 h after surgery (T3) and then 1 day after surgery (T4).
      Native blood samples were analysed using a thrombelastograph Haemoscope 5000
      (Haemoscope Corporation). RESULTS: We did not see any relevant activation of
      fibrinolysis during any stage. Intraoperatively, we showed even more activated
      blood coagulation with consumption of fibrinogen and a reduced TEG percentage
      clot lysis. Only at the first postoperative sample point we saw a trend towards a
      more fibrinolytic state indicated by increasing partial thromboplastin time, LY
      30 and LY-60 values, and a peak of the fibrin degradation product D-dimers. This
      is consistent with a normal reaction to the hypercoagulable state before and is
      unlikely to be due to an intraoperative tissue type plasminogen activator
      release. We found no evidence of an uncontrolled activation of fibrinolysis on
      the day after surgery. On the contrary, alpha-values which indicate the rate of
      clot formation and which increase during hypercoagulation showed the tendency to
      rise slightly compared with the preoperative value. CONCLUSION: Neither standard
      coagulation parameters nor TEG values showed any significant activation of
      fibrinolysis or of hypercoagulation in the preoperative period. Nevertheless,
      hypercoagulation seems to have a substantial clinical impact as it has been shown
      that cardiovascular complications and pulmonary embolism were the most common
      causes of death after retropubic prostatectomy.

PMID- 18339214
TI  - The effects of isoflurane on adrenomedullin-induced haemodynamic responses in
      pithed rats.
AB  - BACKGROUND AND OBJECTIVES: Adrenomedullin is a potent vasodilatory peptide. The
      mechanisms of adrenomedullin-induced responses are via guanine nucleotide
      guanosine 5'-triphosphate-binding protein (G-protein)-coupled receptor activation
      and are similar to those of calcitonin gene-related peptide (CGRP). Previously,
      we reported that sevoflurane and isoflurane inhibit CGRP-induced haemodynamic
      responses. The effects of volatile anaesthetics on adrenomedullin-induced
      haemodynamic responses, however, are unclear. We hypothesized that the volatile
      anaesthetic isoflurane inhibits adrenomedullin-induced haemodynamic responses. We
      studied the effects of isoflurane on adrenomedullin-induced haemodynamic
      responses in pithed rats, which enables us to evaluate the direct cardiovascular
      effects of drugs without interference from centrally mediated circulatory
      reflexes. METHODS: Male Wistar rats were pithed by inserting a stainless-steel
      rod into the spinal cord. Following median sternotomy, a flow probe was placed
      around the ascending aorta to measure aortic blood flow. Mean arterial pressure
      and cardiac output were maintained at approximately 100 mmHg and 50 mL min-1,
      respectively, with continuous infusion of norepinephrine. After 30 min inhalation
      of isoflurane (1%, or 2%) in oxygen, or only oxygen, adrenomedullin (1, 3, 10 or
      30 microg kg-1) was administered intravenously. RESULTS: Adrenomedullin
      administration induced a transient increase followed by a persistent decrease in
      mean arterial pressure and cardiac output. Isoflurane (2%) significantly
      inhibited the initial increase in mean arterial pressure and the later decrease
      in mean arterial pressure and systemic vascular resistance. CONCLUSION:
      Isoflurane inhibits adrenomedullin-induced vasodilation and positive inotropic
      effect in pithed rats. Isoflurane might inhibit the adrenomedullin receptor
      mediated response, which is a common pathway for both actions.

PMID- 18339215
TI  - An evaluation of the contributions by fresh gas flow rate, carbon dioxide
      concentration and desflurane partial pressure to carbon monoxide concentration
      during low fresh gas flows to a circle anaesthetic breathing system.
AB  - BACKGROUND AND OBJECTIVE: Numerous in vitro studies have shown that volatile
      anaesthetics react with desiccated carbon dioxide (CO2) absorbents to produce
      carbon monoxide (CO). The effects of anaesthetic concentration, fresh gas flow
      rate, and the hydration of absorbent or the excretion of CO2 by patients on CO
      production have also been investigated. This work aims to identify the most
      significant one of these factors on CO concentration in a low-flow anaesthesia
      system, without control of the hydration of the absorbents. METHODS: A simulated
      clinical circle anaesthetic breathing system was used to study the CO
      concentration under various conditions. Desflurane was used at three different
      concentrations. Two CO2 flow rates and three fresh gas flow rates were used. The
      absorbent temperatures and hydration were measured simultaneously. RESULTS:
      Desflurane degraded to produce CO in the breathing tube, when the CO2 absorbents
      were not dried beforehand. In this imitation clinical low-flow setting, fresh gas
      flow affected the CO production more than the CO2 did (31.7% vs. 9.5%). The
      actual desflurane partial pressure was not a significant factor. The CO2 flow
      rate explained 18.2% and 54.0% of the variation of the absorbent hydration
      changes (%) and temperature, respectively. CONCLUSIONS: In clinical practice, the
      CO2 production varies among patients and is uncontrollable, but markedly affects
      CO production. The only controllable factor is the fresh gas flow rate if the
      ultimate goal is to reduce the undesirable exposure of patients to CO from the
      breathing tube according to this bench model without counting the oxygen
      consumption.

PMID- 18339216
TI  - The early phase of critical illness is a progressive acidic state due to
      unmeasured anions.
AB  - BACKGROUND AND OBJECTIVE: Stewart's and Fencl's methods have recently been
      proposed to interpret acid-base disorders where traditional theory has proven
      inadequate. Our objectives were to evaluate: (1) the occurrence of acid-base
      disturbances in critically ill patients and their trend over the first 3
      intensive care unit days, (2) whether Stewart's theory offers advantages over the
      traditional theory in the diagnosis of acid-base metabolic disturbances and (3)
      whether variables derived from Stewart's and Fencl's methods offer advantages
      over the traditional method to predict patient mortality. METHODS: A prospective
      cohort study in a general intensive care unit. Blood samples were analysed for
      arterial blood gases, electrolytes and proteins. PaCO2, pH, bicarbonate, base
      excess, standard base-excess, sodium, potassium, chloride, phosphorous, calcium,
      magnesium and lactate were measured. Anion gap, Stewart's and Fencl's variables
      were calculated. RESULTS: When using Stewart's method, metabolic acidosis and
      metabolic alkalosis were found in 92.9% and 93.4% of samples, respectively.
      Corresponding figures obtained with the traditional method were 15% and 18.7%. In
      245 (64.5%) samples, Stewart's method revealed that metabolic acidosis and
      alkalosis were simultaneously present, whereas the traditional method revealed a
      normal acid-base status. Strong ion gap increased significantly over the first 3
      intensive care unit days. Strong ion gap and lactate were independent predictors
      of 28-day mortality. CONCLUSIONS: Metabolic acidosis by unmeasured anions is a
      clinically relevant phenomenon, which is correlated with mortality. Progressive
      metabolic acidosis may be ongoing in the early phase of critical illness despite
      the absence of acidaemia.

PMID- 18339217
TI  - Heat transfer coefficient: Medivance Arctic Sun Temperature Management System vs.
      water immersion.
AB  - BACKGROUND AND OBJECTIVE: To improve heat transfer, the Medivance Arctic Sun
      Temperature Management System (Medivance, Inc., Louisville, CO, USA) features an
      adhesive, water-conditioned, highly conductive hydrogel pad for intimate skin
      contact. This study measured and compared the heat transfer coefficient (h), i.e.
      heat transfer efficiency, of this pad (hPAD), in a heated model and in nine
      volunteers' thighs; and of 10 degrees C water (hWATER) in 33 head-out immersions
      by 11 volunteers. METHODS: Volunteer studies had ethical approval and written
      informed consent. Calibrated heat flux transducers measured heat flux (W m-2).
      Temperature gradient (DeltaT) was measured between skin and pad or water
      temperatures. Temperature gradient was changed through the pad's water
      temperature controller or by skin cooling on immersion. RESULTS: The heat
      transfer coefficient is the slope of W m-2/DeltaT: its unit is W m-2 degrees C-1.
      Average with (95% CI) was: model, hPAD = 110.4 (107.8-113.1), R2 = 0.99, n = 45;
      volunteers, hPAD = 109.8 (95.5-124.1), R2 = 0.83, n = 51; and water immersion,
      hWATER = 107.1 (98.1-116), R2 = 0.86, n = 94. CONCLUSION: The heat transfer
      coefficient for the pad was the same in the model and volunteers, and equivalent
      to hWATER. Therefore, for the same DeltaT and heat transfer area, the Arctic
      Sun's heat transfer rate would equal water immersion. This has important
      implications for body cooling/rewarming rates.

PMID- 18339218
TI  - Isovolaemic haemodilution decreases the shivering threshold in rabbits.
AB  - BACKGROUND AND OBJECTIVE: The inhibition of thermoregulatory control by
      anaesthesia is manifested by reduced vasoconstriction and shivering thresholds.
      As intraoperative bleeding can result in haemodynamic changes, including
      vasoconstriction, we investigated the effect of experimental bleeding on the
      shivering threshold in rabbits. METHODS: Twenty-four rabbits were randomly
      assigned to one of three treatment strategies: (1) no blood removal (control),
      (2) 5 mL kg(-1) isovolaemic blood removal and (3) 10 mL kg(-1) isovolaemic blood
      removal. After tracheal intubation under isoflurane anaesthesia, anaesthesia was
      maintained with 50% nitrous oxide in oxygen. The removed blood volume was
      replaced with the same volume of warm hydroxyethyl starch colloid solution.
      Oesophageal temperature was measured as a core temperature at 1-min intervals.
      After blood removal, the animal's body was cooled at a rate of 2-3 degrees C h(
      1) by perfusing water at 10 degrees C through a U-shaped thermode positioned in
      the colon. Hypothermic shivering was evaluated by visual inspection, and the core
      temperature at which shivering was triggered was identified as the
      thermoregulatory threshold for this response. RESULTS: Just before the cooling,
      the body temperature of the animals was around 38.6 degrees C in all of the three
      groups. The shivering threshold in the control group was 37.2 +/- 0.2 degrees C
      (mean +/- SD). The shivering thresholds in the 5 mL kg(-1) (36.9 degrees +/- 0.3
      degrees C) and 10 mL kg(-1) (36.5 degrees +/- 0.5 degrees C) blood removal groups
      were significantly lower and in proportion with the volume of blood removed than
      that in the control group. CONCLUSION: Isovolaemic haemodilution decreased the
      shivering threshold in rabbits in proportion with the volume of blood removed.

PMID- 18339219
TI  - A benign cause for a unilateral dilated pupil in a critical care patient.

PMID- 18339220
TI  - Sevoflurane consumption--laryngeal mask vs. tracheal intubation.

PMID- 18339221
TI  - Comparing tissue coring potentials of hollow needles without stylet and caudal
      needles with stylet: an experimental study.
AB  - BACKGROUND AND OBJECTIVES: Although the association of tissue coring and
      development of epidermoid tumour has been proposed, the extent and frequency of
      such coring is still controversial and the viability of carried cells has not
      been substantiated. In the present study, we used an experimental model without
      needle removal to investigate the incidence of tissue coring using two different
      needle types. METHODS: We inserted 22-G caudal (n = 34) or 22-G hollow (n = 25)
      needles to the tumour-free areas of fresh modified mastectomy specimens. The
      specimen was stretched and needles were inserted perpendicular to the skin and
      forced to penetrate the full thickness of the specimen. Without removing the
      needle, the needle cavity was then washed with 2 mL of RPMI 1640 with L-Glutamine
      and the washings were collected in a 15-mL falcon tube. The tubes were sealed and
      labelled and processed to obtain cytologic preparations. The slides were
      evaluated under a light microscope. RESULTS: A high rate of epithelial cell
      transportation was noted. All the carried cells were stratum corneum cells with
      no nucleus. No nucleated cells were seen. The incidence of carried cells was
      64.7% and 72.0% in the caudal and hollow needle groups, respectively (P > 0.05).
      CONCLUSION: Only cells from the outermost layer, stratum corneum, which is made
      of dead flat skin cells, were transported with needle puncture. The risk of
      epidermoid tumour development after regional anaesthesia must therefore be low.
      The incidence of transporting non-nucleated stratum corneum cells was similar
      between hollow and caudal needles.

PMID- 18339222
TI  - Docosahexaenoic acid-rich fish oil improves heart rate variability and heart rate
      responses to exercise in overweight adults.
AB  - Dietary fish oil supplementation and regular physical activity can improve
      outcomes in patients with established CVD. Exercise has been shown to improve
      heart rate variability (HRV), a predictor of cardiac death, but whether fish oil
      benefits HRV is controversial. Obese adults at risk of future coronary disease
      have impaired HRV and may benefit from these interventions. We evaluated the
      effect of DHA-rich tuna fish oil supplementation with and without regular
      exercise on HRV in sedentary, overweight adults with risk factors for coronary
      disease. In a randomised, double-blind, parallel comparison, sixty-five
      volunteers consumed 6 g fish oil/d (DHA 1.56 g/d, EPA 0.36 g/d) or sunflower-seed
      oil (placebo) for 12 weeks. Half of each oil group also undertook regular
      moderate physical activity (3 d/week for 45 min, at 75 % of age-predicted maximal
      heart rate (HR)). Resting HR and the HR response to submaximal exercise were
      measured at weeks 0, 6 and 12. In forty-six subjects, HRV was also assessed by
      power spectrum analysis of 20 min electrocardiogram recordings taken supine at
      baseline and 12 weeks. Fish oil supplementation improved HRV by increasing high
      frequency power, representing parasympathetic activity, compared with placebo (P
      = 0.01; oil x time interaction). It also reduced HR at rest and during submaximal
      exercise (P = 0.008; oil x time interaction). There were no significant fish oil
      x exercise interactions. Dietary supplementation with DHA-rich fish oil reduced
      HR and modulated HRV in keeping with an improved parasympathetic-sympathetic
      balance in overweight adults with risk factors for future coronary disease.

PMID- 18339223
TI  - The role of 5-HT2A and 5-HT2C receptors in the signal attenuation rat model of
      obsessive-compulsive disorder.
AB  - Serotonin 5-HT2A and 5-HT2C receptors have been implicated in the pathophysiology
      of obsessive-compulsive disorder (OCD) and in the mechanism mediating the anti
      compulsive effects of serotonin reuptake inhibitors. Yet it is currently unclear
      whether activation or blockade of these receptors would have an anti-compulsive
      effect. The present study tested the effects of 5-HT2A and 5-HT2C activation and
      blockade in the signal attenuation rat model of OCD. In this model, 'compulsive'
      behaviour is induced by attenuating a signal indicating that a lever-press
      response was effective in producing food. Experiments1-4 revealed that systemic
      administration of the 5-HT2C antagonist RS 102221 (2 mg/kg) selectively decreases
      compulsive lever-pressing, whereas systemic administration of the 5-HT2A
      antagonist MDL11,939(0.2-5 mg/kg) or of the 5-HT2A/2C agonist DOI (0.05-5 mg/kg)
      did not have a selective effect on this behaviour. Experiments 5 and 6 found that
      systemic co-administration of DOI (0.5 mg/kg) withMDL11,939 (1 mg/kg) or with RS
      102221 (2 mg/kg) had a non-selective effect on lever-press responding,with the
      former manipulation increasing and the latter manipulation decreasing lever
      pressing. Finally,experiment 7 demonstrated that administration of RS 102221
      directly into the orbitofrontal cortex also exerts an anti-compulsive effect. The
      results of these experiments suggest that blockade of 5-HT2Creceptors may have an
      anti-compulsive effect in OCD patients, and that this effect may be mediated by5
      HT2C receptors within the orbitofrontal cortex.

PMID- 18339224
TI  - Predictors of trying to lose weight among overweight and obese Mexican-Americans:
      a signal detection analysis.
AB  - OBJECTIVE: Signal detection analysis, a form of recursive partitioning, was used
      to identify combinations of sociodemographic and acculturation factors that
      predict trying to lose weight in a community-based sample of 957 overweight and
      obese Mexican-American adults (ages 18-69 years). DESIGN: Data were pooled from
      the 2004 and 2006 Behavioral Risk Factor Surveillance System conducted in a low
      income, semi-rural community in California. RESULTS: Overall, 59 % of the
      population reported trying to lose weight. The proportion of adults who were
      trying to lose weight was highly variable across the seven mutually exclusive
      groups identified by signal detection (range 30-79 %). Significant predictors of
      trying to lose weight included BMI, gender, age and income. Women who were very
      overweight (BMI > 28.5 kg/m2) were most likely to be trying to lose weight (79
      %), followed by very overweight higher-income men and moderately overweight (BMI
      = 25.0-28.5 kg/m2) higher-income women (72 % and 70 %, respectively). Moderately
      overweight men, aged 28-69 years, were the least likely to be trying to lose
      weight (30 %), followed by moderately overweight lower-income women (47 %) and
      very overweight lower-income men (49 %). The latter group is of particular
      concern since they have characteristics associated with medical complications of
      obesity (low education and poor access to medical care). CONCLUSIONS: Our
      findings highlight opportunities and challenges for public health professionals
      working with overweight Mexican-American adults - particularly lower-income
      adults who were born in Mexico - who are not trying to lose weight and are
      therefore at high risk for obesity-related co-morbidities.

PMID- 18339225
TI  - Towards health-promoting and environmentally friendly regional diets - a Nordic
      example.
AB  - BACKGROUND: Because most of the top determinants of the worldwide burden of
      disease are diet-related, the promotion of healthful diets is important for
      population health across the world. Furthermore, changes in eating habits may
      contribute to preservation of the environment. OBJECTIVE: In the present paper it
      is argued that the translation of health-promoting dietary recommendations into
      practical recommendations for healthful eating should be more tailored to
      regional circumstances. This will promote population health as well as help
      preserve cultural diversity in eating habits and contribute to more
      environmentally friendly eating. A regional Nordic diet, mimicking the
      Mediterranean diet to some extent, is presented as an example. CONCLUSION: A
      theoretically health-enhancing Nordic diet is possible including six evidence
      based ingredients: (i) native berries; (ii) cabbage; (iii) native fish and other
      seafood; (iv) wild (and pasture-fed) land-based animals; (v) rapeseed oil; and
      (vi) oat/barley/rye.

PMID- 18339226
TI  - Association between commercial television exposure and fast-food consumption
      among adults.
AB  - OBJECTIVE: To examine the association between television advertising exposure and
      adults' consumption of fast foods. DESIGN: Cross-sectional telephone survey.
      Questions included measures of frequency of fast-food consumption at different
      meal times and average daily hours spent watching commercial television.
      SUBJECTS/SETTING: Subjects comprised 1495 adults (41 % response rate) aged >or=18
      years from Victoria, Australia. RESULTS: Twenty-three per cent of respondents
      usually ate fast food for dinner at least once weekly, while 17 % consumed fast
      food for lunch on a weekly basis. The majority of respondents reported never
      eating fast food for breakfast (73 %) or snacks (65 %). Forty-one per cent of
      respondents estimated watching commercial television for <or=1 h/d (low viewers);
      29 % watched for 2 h/d (moderate viewers); 30 % watched for >or=3 h/d (high
      viewers). After adjusting for demographic variables, high viewers were more
      likely to eat fast food for dinner at least once weekly compared with low viewers
      (OR = 1.45; 95 % CI 1.04, 2.03). Both moderate viewers (OR = 1.53; 95 % CI 1.01,
      2.31) and high viewers (OR = 1.81; 95 % CI 1.20, 2.72) were more likely to eat
      fast food for snacks at least once weekly compared with low viewers. Commercial
      television viewing was not significantly related (P > 0.05) to fast-food
      consumption at breakfast or lunch. CONCLUSIONS: The results of the present study
      provide evidence to suggest that cumulative exposure to television food
      advertising is linked to adults' fast-food consumption. Additional research that
      systematically assesses adults' behavioural responses to fast-food advertisements
      is needed to gain a greater understanding of the mechanisms driving this
      association.

PMID- 18339227
TI  - Tissue Doppler imaging in rheumatic carditis.
AB  - OBJECTIVE: Our study was undertaken to assess cardiac functions by tissue Doppler
      echocardiography in patient with primary episode of rheumatic carditis. METHODS:
      We divided 82 patients with rheumatic carditis were divided in two groups; 50
      patients with mild and 32 patients with mitral regurgitation of grade two or
      more. A control group consisted of 30 healthy children free of any disease. All
      children underwent conventional and tissue Doppler echocardiography initially and
      at the time of the follow-up examination. RESULTS: Myocardial systolic wave
      velocity of the mitral annulus was significantly higher in patients with mitral
      regurgitation of grade two or more when compared to the control group, but was
      not different between patients with mild mitral regurgitation and healthy
      subjects at the time of the initial attack. Myocardial precontraction time,
      myocardial contraction time, and the ratio of myocardial precontraction and
      contraction times were significantly prolonged, and the systolic myocardial
      velocity of the mitral annulus was significantly decreased in patients with
      mitral regurgitation of grade two or more at the time of the follow-up
      examination. The myocardial systolic wave velocity was significantly lower, and
      myocardial precontraction time, myocardial contraction time, and the ratio of the
      precontraction and contraction times, were significantly longer or greater
      between patients with grade two or more mitral regurgitation and the control
      group at follow-up examination. CONCLUSION: We detected subclinical systolic
      dysfunction of the left ventricle in children with a primary episode of rheumatic
      carditis due to ongoing ventricular volume overload. Tissue Doppler imaging
      provides a quantifiable indicator useful for cardiac monitoring of disease during
      the period of follow up.

PMID- 18339228
TI  - Percutaneous implantation of pulmonary valves for treatment of right ventricular
      outflow tract dysfunction.

PMID- 18339231
TI  - Estimating and correcting mie scattering in synchrotron-based microscopic fourier
      transform infrared spectra by extended multiplicative signal correction.
AB  - We present an approach for estimating and correcting Mie scattering occurring in
      infrared spectra of single cells, at diffraction limited probe size, as in
      synchrotron based microscopy. The Mie scattering is modeled by extended
      multiplicative signal correction (EMSC) and subtracted from the vibrational
      absorption. Because the Mie scattering depends non-linearly on alpha, the product
      of the radius and the refractive index of the medium/sphere causing it, a new
      method was developed for estimating the Mie scattering by EMSC for unknown radius
      and refractive index of the Mie scatterer. The theoretically expected Mie
      contributions for a range of different alpha values were computed according to
      the formulae developed by Van de Hulst (1957). The many simulated spectra were
      then summarized by a six-dimensional subspace model by principal component
      analysis (PCA). This subspace model was used in EMSC to estimate and correct for
      Mie scattering, as well as other additive and multiplicative interference
      effects. The approach was applied to a set of Fourier transform infrared (FT-IR)
      absorbance spectra measured for individual lung cancer cells in order to remove
      unwanted interferences and to estimate ranges of important alpha values for each
      spectrum. The results indicate that several cell components may contribute to the
      Mie scattering.

PMID- 18339232
TI  - Bacillus spore classification via surface-enhanced Raman spectroscopy and
      principal component analysis.
AB  - Surface-enhanced Raman spectroscopy (SERS) can provide rapid fingerprinting of
      biomaterial in a nondestructive manner. The adsorption of colloidal silver to
      biological material suppresses native biofluorescence while providing
      electromagnetic surface enhancement of the normal Raman signal. This work
      validates the applicability of qualitative SER spectroscopy for analysis of
      bacterial species by utilizing principal component analysis (PCA) to show
      discrimination of biological threat simulants, based upon multivariate
      statistical confidence limits bounding known data clusters. Gram-positive
      Bacillus spores (Bacillus atrophaeus, Bacillus anthracis, and Bacillus
      thuringiensis) are investigated along with the Gram-negative bacterium Pantoea
      agglomerans.

PMID- 18339233
TI  - New Raman spectrometer using a digital micromirror device and a photomultiplier
      tube detector for rapid on-line industrial analysis. Part I: description of the
      prototype and preliminary results.
AB  - In this paper, a prototype of a new generation of Raman spectrometers, based on
      the use of a monochromator, a digital micromirror device as light modulator, and
      a photomultiplier tube as detector of the Raman light, is described. This
      spectrometer, containing no moving parts, is inexpensive, robust, and very
      precise. New in concept, this spectrometer makes it possible to record, in
      addition to classical Raman spectra, the intensity at several selected points of
      the spectrum and/or the total intensity in several selected intervals at the same
      time with great accuracy, thus giving new possibilities for analytical
      applications. Also, the work presented demonstrates the possibilities of this
      very simple prototype for rapid on-line industrial analysis, with an example of
      quantitative analysis of binary and ternary mixtures of xylene isomers. The
      precision obtained is satisfactory (errors of prediction approximately 3% in 5-6
      seconds per sample).

PMID- 18339234
TI  - New Raman spectrometer using a digital micromirror device and a photomultiplier
      tube detector for rapid on-line industrial analysis. Part II: Choice of
      analytical methods.
AB  - In this paper, the performances of four improved analytical methods (backward
      stepwise selection of peak intensities, sum of characteristic peaks of a
      component, moving window partial least squares, and genetic algorithms) using
      wavelength selection for the analysis of xylene mixtures by Raman spectroscopy
      are tested for further use on the new "digital micromirror device associated with
      a photomultiplier tube" Raman spectrometer. It is shown that the errors of
      prediction using only a few selected points (from 4 to 49 depending on the
      method) are almost the same as when using the whole spectral range (1050 points).
      Compared to the last two methods, the "backward stepwise selection of peak
      intensities" and "sum of characteristic peaks of a component" methods are robust
      under industrial conditions and appear to be well suited for chemical
      quantitative analysis with the new Raman spectrometer, which allows the
      measurements of the total intensity to be made simultaneously for a number of pre
      selected frequencies. Results show that the errors of prediction can be near to
      or even lower than 2%.

PMID- 18339235
TI  - Multipass capillary cell for enhanced Raman measurements of gases.
AB  - A simple Raman multipass capillary cell (MCC) is described that gives 12- to 30
      fold signal enhancements for non-absorbing gases. The cell is made by coating the
      inside of 2-mm inner diameter silica capillary tubes with silver. The device is
      very small and suitable for remote and in situ Raman measurements with optical
      fibers. Application of the MCC is similar to previously described liquid core
      waveguides but, unlike the latter devices, the MCC is generally more applicable
      to a wide range of non-absorbing gases.

PMID- 18339236
TI  - Guest aggregation within poly(L-lactic acid)/pluronic P104 thin films.
AB  - Rhodamine 6G (R6G) doped thin films composed of poly(L-lactic acid) (PLLA) and
      Pluronic P104 were spin cast onto glass microscope slides and characterized by
      ultraviolet-visible, steady-state, and time-resolved fluorescence spectroscopy.
      The results show that R6G aggregation within the film increases as the R6G
      concentration and P104 loading increases. These results suggest an approach for
      studying drug distributions (monomers, aggregates) within biodegradable polymer
      formulations.

PMID- 18339237
TI  - Two-dimensional correlation infrared spectroscopic study on the crystallization
      and gelation of poly(vinylidene fluoride) in cyclohexanone.
AB  - Poly(vinylidene fluoride) (PVDF) converts easily into a thermo-reversible gel
      through crystallization by standing at room temperature in cyclohexanone. In this
      study, the Fourier transform infrared (FT-IR) spectra were measured continuously
      at room temperature during the conversion of the solution into a gel. The IR
      difference spectra derived from these spectra by absorbance subtraction clearly
      indicate the presence of PVDF alpha-crystallites in the gel due to the presence
      of absorption bands corresponding to the TG+TG- conformation of the alpha-phase.
      In the time interval from 25 to 45 min after the beginning of the experiment, the
      IR bands of PVDF increased dramatically, indicating the conversion of polymer
      chains from random statistical coils to the ordered TG+TG- conformation (alpha
      form). In the time interval from 45 to 90 min, the IR bands of PVDF increased
      slowly, reflecting no further crystallization. Using two-dimensional (2D) IR
      analysis, it could be shown that the nu(C=O) absorption band of cyclohexanone
      changed during the gelation process. During the conformational ordering process
      (25-45 min), the nu(C=O) absorption band of the cyclohexanone dimer (1707 cm(-1))
      decreased while the corresponding band of the monomer at 1718 cm(-1) increased.
      Furthermore, a new band at 1695 cm(-1) increased, which could be assigned to C=O
      groups of the solvent interacting with the CF2 groups in the polymer chain. The
      bands of the crystalline PVDF share positive cross-peaks with the bands of
      cyclohexanone, which indicates that the chain of PVDF changed prior to the
      cyclohexanone molecules during the conformational ordering process. However,
      these positive cross-peaks disappeared during the crystallization process, which
      means that the chain of PVDF changed synchronously with the solvent molecules. As
      for the bands of PVDF chains, the band at 762 cm(-1) varied prior to the bands at
      873 cm(-1) and 796 cm(-1) during the conformational ordering process. The 762 cm(
      1) absorption is assigned to the CF2 group of PVDF, the 873 cm(-1) absorption
      involves the C-C group of PVDF, and the 796 cm(-1) band is attributed to the CH2
      groups of PVDF. Thus, the CF2 functionalities change faster than the C-C and CH2
      groups. However, the correlation cross-peaks between 762 cm(-1) and 873 cm(-1)
      and at 796 cm(-1) disappeared during the later state of the gelation process. At
      the same time, the bands of PVDF and solvent still varied, which suggests that it
      is a physical interaction process between PVDF chain and solvent.

PMID- 18339238
TI  - Discrimination of soil-borne fungi using fourier transform infrared attenuated
      total reflection spectroscopy.
AB  - Fourier transform infrared (FT-IR) attenuated total reflection (ATR) spectroscopy
      was used to discriminate five commonly encountered soil-borne fungi that cause
      severe economic damage to agriculture: Colletotrichum, Fusarium, Pythium,
      Rhizoctonia, and Verticillium. Contrary to previous studies related to
      microorganism discrimination using FT-IR-ATR spectroscopy, the pathogen samples
      were not dried on the ATR crystal, which is a time-consuming operation. Rather,
      after removing some pathogen filaments from the solution using tweezers, these
      were placed directly on a flat ATR crystal and pressure was applied using a
      pressure clamp. Following water subtraction, baseline correction, and
      normalization of the spectra, principal component analysis was used as a data
      reduction step and canonical variate analysis was used for discrimination.
      Discrimination was performed at the genus level and at the strain level for
      Colletotrichum. For discrimination between the five fungi at the genus level, the
      success rate for the validation samples ranged from 75% to 89%. For
      discrimination between the two Colletotrichum strains, the success rate was 78%.
      Comparison with spectra of similar fungi dried on the ATR crystal showed that
      both types of spectra were very similar, indicating that drying the samples on
      the ATR crystal is not required and can be replaced by mathematical post
      processing of the spectra. For routine analyses that involve rapid screening of
      very large amounts of samples, this approach allows for increasing significantly
      the number of samples that can be analyzed daily.

PMID- 18339239
TI  - Molecular spectroscopic study of river nile sediment in the greater cairo region.
AB  - The greater Cairo region is the most populated area in Egypt. The aquatic
      environment of the Nile River in this area is being affected by industrial
      activities. The study of the molecular structure of sediment may provide a good
      trace for such changes. Both Fourier transform infrared spectroscopy (FT-IR) and
      density functional theory (DFT) were used to study the effect of industrial waste
      disposal south of Cairo on the molecular structure of Nile River sediment. Four
      seasonal samples were collected from six sites covering 75 km along the Nile
      River. Grain sizes of 200 microm, 125 microm, 65 microm, and 32 microm,
      respectively, were examined. The results indicate that hydrated aluminum
      hydroxide controls the distribution of organic matter in the different grain
      sizes. Furthermore, the hydration of phenol may take place in grain sizes lower
      than 200 microm, which is indicated by the OH stretching at 3550 cm(-1) and
      verified by the obtained model. The formation of metal carboxylate bonds at 1638
      cm(-1) (asymmetric) and 1382 cm(-1) (symmetric) indicate the possible interaction
      between heavy metals and other organic structures, mainly humic substances.

PMID- 18339240
TI  - Fiber-optic infrared reflection absorption spectroscopy for trace analysis on
      surfaces of varying roughness. Part II: Acetaminophen on stainless steel.
AB  - Investigations of the effects of surface roughness on the utility of grazing
      angle Fourier transform infrared reflection absorption spectroscopy (IRRAS) as a
      method for quantifying trace contamination of metal surfaces have been extended
      to acetaminophen, a model active pharmaceutical agent, on 316 stainless steel.
      The effects are more complicated than for the surfactant sodium dodecyl sulfate
      (SDS) on stainless steel; they include a strong surface-finish dependence of
      sensitivity and nonlinear behavior at surface loadings above approximately 1-2
      microg cm(-2). Using data from samples in the loading range 0-0.5 microg cm(-2),
      unbiased partial least squared calibrations can be readily achieved for
      individual surface finishes with detection limits of L(D) approximately 0.15
      microg cm(-2). However, as found for SDS on stainless steel, models built using
      data from samples of mixed surface roughness are more problematic.

PMID- 18339241
TI  - Narrow-line waveguide terahertz time-domain spectroscopy of aspirin and aspirin
      precursors.
AB  - Low frequency vibrational modes of pharmaceutical molecules are dependent on the
      molecule as a whole and can be used for identification purposes. However,
      conventional Fourier transform far-infrared spectroscopy (FT-IR) and terahertz
      time-domain spectroscopy (THz-TDS) often result in broad, overlapping features
      that are difficult to distinguish. The technique of waveguide THz-TDS has been
      recently developed, resulting in sharper spectral features. Waveguide THz-TDS
      consists of forming an ordered polycrystalline film on a metal plate and
      incorporating that plate in a parallel-plate waveguide, where the film is probed
      by THz radiation. The planar order of the film on the metal surface strongly
      reduces the inhomogeneous broadening, while cooling the waveguide to 77 K reduces
      the homogeneous broadening. This combination results in sharper absorption lines
      associated with the vibrational modes of the molecule. Here, this technique has
      been demonstrated with aspirin and its precursors, benzoic acid and salicylic
      acid, as well as the salicylic acid isomers 3- and 4-hydroxybenzoic acid.
      Linewidths as narrow as 20 GHz have been observed, rivaling single crystal
      measurements.

PMID- 18339242
TI  - A multi-source portable light emitting diode spectrofluorometer.
AB  - A portable luminescence spectrofluorometer weighing only 1.5 kg that uses
      multiple light emitting diodes (LEDs) as excitation sources was developed and
      evaluated. Excitation using a sequence of seven individual broad-band LED
      emission sources enabled the generation of excitation-emission spectra using a
      light weight (<1.5 kg) spectrometer. Limits of detection for rhodamine 6G,
      rhodamine B, and fluorescein were 2.9, 3.2, and 11.0 nM, respectively. Generation
      of excitation-emission matrices (EEMs) enabled the analysis of samples containing
      mixtures of rhodamine B and fluorescein. Buffered saline plant and animal feed
      extracts were also analyzed using this instrument. These samples included the
      woody plants Pistacia lentiscus (Evergreen pistache or Mastic) and Philyria
      latifolia, and the herbaceous species Medicago sativa (alfalfa), Trifolium spp.
      (clover), and a feed concentrate. Application of multi-way principal component
      analysis (MPCA) to the resulting three-dimensional data sets enabled discernment
      among these various diet constituents.

PMID- 18339243
TI  - Nitrogen gas purging for the deoxygenation of polyaromatic hydrocarbon solutions
      in cyclohexane for routine fluorescence analysis.
AB  - During routine fluorescence analysis, the presence of dissolved oxygen in
      solutions can result in the dynamic quenching of a fluorophore's emission through
      collisional deexcitation of the fluorophore's excited state. In order to avoid
      this type of fluorescence quenching, dissolved oxygen is often removed from
      solutions by an inert gas purging procedure. However, the details and
      quantification of this purging process are often limited in fluorescence studies.
      In this work, standard 10 mm x 10 mm fluorescence cuvettes are filled with
      polyaromatic hydrocarbon (PAH) solutions in cyclohexane and purged using nitrogen
      gas, and the experimental purging parameters (nitrogen flow rate, amount of
      volatile solvent loss, and rate of oxygen removal) are measured and analyzed. For
      experimental conditions similar to those used in this study, we are able to
      provide useful guidelines for the deoxygenation of solutions, specifically the
      purge times required for solutions of fluorophores with various fluorescence
      lifetimes. Enhancement factors, or F(0)/F values (the ratio of fluorescence
      intensity of a completely deoxygenated solution to the fluorescence intensity of
      an aerated solution), for chrysene, phenanthrene, naphthalene, and pyrene
      solutions in cyclohexane were found to be 3.61 +/- 0.02, 4.17 +/- 0.02, 7.63 +/-
      0.07, and 21.81 +/- 0.35, respectively.

PMID- 18339244
TI  - Rapid detection of low concentrations of aqueous species in the presence of
      spectral overlap using planar array infrared spectroscopy.

PMID- 18339245
TI  - Indirect determination of molecular chlorine by fourier transform infrared
      spectrometry.

PMID- 18339246
TI  - Implications of area normalization of multi-component spectra.

PMID- 18339247
TI  - Anti-atherosclerotic and anti-diabetic properties of probucol and related
      compounds.
AB  - Probucol is a diphenolic compound with anti-oxidant and anti-inflammatory
      properties that reduces atherosclerosis and restenosis. Unfortunately, adverse
      effects on blood lipoproteins and cardiac electrophysiology have curtailed its
      use as a drug. Compounds related to probucol that have improved efficacy without
      the adverse effects offer promise as novel therapies of cardiovascular disease.
      Recent results suggest that these compounds may be used for the prevention of
      type 2 diabetes, a disease that is increasing in prevalence and importance world
      wide. In this review, the molecular mechanisms underlying the beneficial
      activities of probucol and related compounds are described.

PMID- 18339248
TI  - Dose-dependent modulation of systemic lipid peroxidation and activity of anti
      oxidant enzymes by vitamin E in the rat.
AB  - The objective of this work was to examine the time-dependent pro-oxidant versus
      antioxidant effect of various doses of vitamin E used commonly in experimental
      studies. Erythrocyte activity of superoxide dismutase (SOD), glutathione
      peroxidase (GPX), catalase (CAT) and plasma lipid peroxidation levels were
      investigated following biweekly intramuscular administration of 100, 300 and 600
      mg/kg of vitamin E at a baseline time point, and additionally at 2, 4 and 6 weeks
      after initiating treatment. Vitamin E had an antioxidant effect when administered
      at low doses over short time periods, and increased the activity of antioxidant
      enzymes. At higher doses and over longer time periods, it increased the level of
      lipid peroxidation, and attenuated the activity of antioxidant enzymes. These
      results suggest that time-dependent variations in vitamin E effects should be
      considered in design and interpretation of experimental antioxidant studies, as
      well as during clinical trials.

PMID- 18339249
TI  - Protection of arsenic-induced testicular oxidative stress by arjunolic acid.
AB  - Arsenic-induced tissue damage is a major concern to the human population. An
      impaired antioxidant defense mechanism followed by oxidative stress is the major
      cause of arsenic-induced toxicity, which can lead to reproductive failure. The
      present study was carried out to investigate the preventive role of arjunolic
      acid, a triterpenoid saponin isolated from the bark of Terminalia arjuna, against
      arsenic-induced testicular damage in mice. Administration of arsenic (in the form
      of sodium arsenite, NaAsO(2), at a dose of 10 mg/kg body weight) for 2 days
      significantly decreased the intracellular antioxidant power, the activities of
      the antioxidant enzymes, as well as the levels of cellular metabolites. In
      addition, arsenic intoxication enhanced testicular arsenic content, lipid
      peroxidation, protein carbonylation and the level of glutathione disulfide
      (GSSG). Exposure to arsenic also caused significant degeneration of the
      seminiferous tubules with necrosis and defoliation of spermatocytes. Pretreatment
      with arjunolic acid at a dose of 20 mg/kg body weight for 4 days could prevent
      the arsenic-induced testicular oxidative stress and injury to the histological
      structures of the testes. Arjunolic acid had free radical scavenging activity in
      a cell-free system and antioxidant power in vivo. In summary, the results suggest
      that the chemopreventive role of arjunolic acid against arsenic-induced
      testicular toxicity may be due to its intrinsic antioxidant property.

PMID- 18339250
TI  - 24-hour rhythms in oxidative stress during hepatocarcinogenesis in rats: effect
      of melatonin or alpha-ketoglutarate.
AB  - To compare the effects of alpha-ketoglutarate (alpha-KG) and melatonin on 24-h
      rhythmicity of oxidative stress in N-nitrosodiethylamine (NDEA)-injected Wistar
      male rats, melatonin (5 mg/kg i.p.) or alpha-KG (2 g/kg through an intragastric
      tube) was given daily for 20 weeks. In blood collected at 6 time points during a
      24-h period, serum activity of aspartate transaminase (AST) and alanine
      transaminase (ALT) and the levels of alpha-fetoprotein (alpha-FP) were measured
      as markers of liver function. To assess lipid peroxidation and the antioxidant
      status, plasma levels of thiobarbituric acid reactive substances (TBARS) and of
      reduced glutathione (GSH) were measured, together with the activity of
      erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase
      (GPx) and glutathione S-transferase (GST). NDEA augmented mesor and amplitude of
      rhythms in AST and ALT activity and plasma alpha-FP levels and mesor values of
      plasma TBARS, while decreasing mesor values of plasma GSH and erythrocyte SOD,
      CAT, GPx and GST. Acrophases were delayed by NDEA in all cases except for alpha
      FP rhythm, which became phase-advanced. Co-administration of melatonin or alpha
      KG partially counteracted the effects of NDEA. Melatonin decreased mesor of
      plasma TBARS and augmented mesor of SOD activity. The results indicate that
      melatonin and alpha-KG are effective in protecting from NDEA-induced perturbation
      of 24-h rhythms in oxidative stress. Melatonin augmented antioxidant defense in
      rats.

PMID- 18339251
TI  - Studies on cellular resilience and adaptation following acute and repetitive
      exposure to ozone in cultured human epithelial (HeLa) cells.
AB  - Ozone is used to treat several medical conditions, while the underlying
      mechanisms of action are sometimes poorly understood. In the current study, we
      exposed cultured human epithelial (HeLa) cells acutely and repeatedly to ozone
      and investigated the effects thereof on cell viability. The involvement of anti
      apoptotic pathways in observed adaptive responses to ozone were investigated by
      employing the Akt inhibitor (-)-deguelin. Cells were exposed to an ozone
      saturated physiological solution using various dosing regimens, including acute
      exposure and various repetitive exposures. Cell viability was determined with
      Trypan Blue or MTT tests, or by a DNA-fragmentation (comet) assay. Acute ozone
      exposure compromised cell membrane integrity severely, while adaptation to
      reverse an initial reduction in mitochondrial activity was observed. Repetitive,
      short-duration exposures followed by a single long-duration exposure to ozone
      furnished a protective adaptation that was reversed by Akt inhibition.
      Extracellular and intracellular damage (and adaptation) occurs differentially.
      While acute ozone may decrease cell viability, multiple preexposures up-regulates
      cellular plasticity via induction of anti-apoptotic pathways in a treatment
      regimen-specific manner.

PMID- 18339252
TI  - Outlook: metformin use in infertile patients with polycystic ovary syndrome: an
      evidence-based overview.
AB  - Metformin is an insulin sensitizer currently used for treating type-2 diabetes
      mellitus and recently administered for inducing ovulatory menstrual cycles in
      oligo-amenorrhoeic patients with polycystic ovary syndrome (PCOS). The aim of the
      present review is to describe the efficacy of metformin as an ovulation inducer
      on the basis of the most important evidence-based medicine supported data,
      including meta-analyses and randomized controlled trials. Specifically, we
      reviewed the uses of metformin as first- and second-step treatment for PCOS
      related anovulatory infertility and as co-treatment in infertile PCOS patients
      who receive gonadotrophins. To date, there is evidence that metformin is
      effective for restoring normal menstrual cycles in anovulatory PCOS patients, and
      that it is more effective and cheaper than laparoscopic ovarian drilling as the
      second therapeutic step in PCOS patients previously defined as resistant to
      clomiphene citrate. Co-administration of metformin in PCOS patients treated with
      gonadotrophin improves the mono-ovulation rate and can prevent ovarian
      hyperstimulation syndrome in patients treated with gonadotrophins for IVF cycles.

PMID- 18339253
TI  - Cryopreservation of human ovarian tissue: effect of spontaneous and initiated ice
      formation.
AB  - This investigation compared conventional freezing of human ovarian tissue using
      either spontaneous or initiated ('seeded') ice formation. Biopsies of ovarian
      tissue were obtained from women with indications for chemotherapy or
      radiotherapy. Small pieces of experimental tissue were randomly distributed into
      three groups that were then subjected to different treatments prior to culture in
      vitro for 16 days: the control group, no treatment, cultured immediately after
      biopsy (group 1); cryopreservation/thawing with spontaneous ice formation (group
      2); and cryopreservation/thawing with initiated ice formation (group 3). Follicle
      viability and hormonal activity were then evaluated. There was no significant
      difference between groups regarding the concentration of oestradiol 17-beta in
      the culture supernatant, whereas progesterone concentration was significantly (P
      < 0.05) higher in group 1 compared with group 2 or 3. There was a significant (P
      < 0.05) difference in primordial and primary follicle density between all of the
      groups (group 1 having the highest and group 2 having the lowest) and group 2 had
      significantly (P < 0.05) fewer normal grade follicles than the other two groups.
      For optimal cryopreservation of human ovarian tissue, the protocol of
      conventional freezing should therefore include a step of initiated ice formation.

PMID- 18339254
TI  - Two successful pregnancies obtained following oocyte vitrification and embryo re
      vitrification.
AB  - Recent clinical reports not only show that cryopreserved embryos can be
      successfully used for human fertility treatment, but also that cryopreserved
      oocytes may be used successfully as an adjunct to human assisted reproductive
      technologies. Vitrification is known to establish a glass-like solid state during
      the cooling process. The high concentration of cryoprotectants and an extremely
      rapid rate of cooling are responsible for the formation of the solid state, and
      also prevent formation of intracellular ice crystals. Hence, in theory,
      vitrification should minimize cryo-injuries, and therefore has great promise for
      oocyte and embryo cryopreservation. This article describes two pregnancies from
      vitrified-warmed blastocysts obtained after intracytoplasmic sperm injection
      fertilization of vitrified-warmed oocytes. Vitrification was employed to
      cryopreserve the oocytes and the subsequent blastocysts. The results present the
      intriguing implication that vitrification may serve as an efficient method for
      clinical oocyte cryopreservation and embryo re-cryopreservation.

PMID- 18339255
TI  - Anti-FSH antibodies associate with poor outcome of ovarian stimulation in IVF.
AB  - FSH is required for spontaneous folliculogenesis and is widely used in ovarian
      stimulation in IVF. Previously, increased concentrations of antibodies against
      FSH (anti-FSH) have been demonstrated in infertile women. This study aimed to:
      (i) assess the possible association of anti-FSH with an adverse outcome of IVF
      with regard to clinical parameters characterizing the ovarian reserve; and (ii)
      compare serum and follicular fluid (FF) anti-FSH concentrations in relation to
      follicle size and endocrine markers. IVF patients (n = 182) subjected to
      gonadotrophin-releasing hormone-antagonist protocol were assessed for anti-FSH
      using enzyme-linked immunosorbent assay. Increased concentrations of serum anti
      FSH immunoglobulin (Ig)G and IgA were associated with impaired ovarian
      stimulation outcome, with cut-off values <1.0 arbitrary units predicting poor
      ovarian response (<or=3 oocytes) (adjusted odds ratio for IgG = 6.95, P = 0.005
      and IgA = 3.60, P = 0.039). FF anti-FSH IgG and IgA were positively associated
      with serum anti-FSH concentrations and FSH concentration in FF. Additionally, FF
      anti-FSH IgG increased with follicle growth (linear regression coefficient =
      0.02, P = 0.022). Collectively, these data suggest that serum anti-FSH antibodies
      are associated with poor ovarian response to FSH stimulation in IVF, with anti
      FSH IgA and IgG potentially exerting a local FSH antagonizing effect in maturing
      follicles.

PMID- 18339257
TI  - Craig Venter creates life by piecing together a giant DNA jigsaw.

PMID- 18339256
TI  - CYP1A1 gene polymorphism and polycystic ovary syndrome.
AB  - The aim of this study was to assess the rates of variant alleles of cytochrome
      P4501A1 (CYP1A1) in patients with polycystic ovary syndrome (PCOS). It was
      designed as a case-control study in Hacettepe University, Faculty of Medicine,
      Department of Obstetrics and Gynecology and Genetics. Forty-eight patients with
      PCOS served as the study group. Ninety-six regularly cycling women with no
      clinical and biochemical evidence of hyperandrogenism and polycystic ovary
      appearance served as the controls. The CYP1A1 variant alleles of all patients
      were determined via polymerase chain reaction. The rate of the CYP1A1 isoleucine
      (Ile)/valine (Val) allele was significantly higher in patients with PCOS than in
      the controls (OR: 7.8, 95% CI: 3.45-17.52, P < 0.001). However, there was no
      statistically significant difference in the distribution of Val/Val genotype (OR:
      4.0, 95% CI: 0.60-26.73). The rate of any Val genotype (Ile/Val or Val/Val) was
      significantly higher in patients with PCOS compared with the control group (OR:
      7.4, 95% CI: 3.33-16.46, P < 0.001). In conclusion, the patients with PCOS had a
      7.8-fold higher frequency of CYP1A1 Ile/Val genotype and a 7.4-fold higher
      frequency of CYP1A1 of any Val genotype (Ile/Val or Val/Val).

PMID- 18339258
TI  - Vaginal gel versus intramuscular progesterone for luteal phase supplementation: a
      prospective randomized trial.
AB  - The aim of this randomized study was to compare the efficacy of intramuscular
      progesterone (IMP) and progesterone in vaginal gel (VGP) at two different doses
      for luteal support in IVF. A total of 412 patients, aged between 28 and 37 years,
      were randomized into three groups. The day after oocyte retrieval each patient
      began supplementation with one of the following: IMP 50 mg daily (150 patients),
      VGP 90 mg once daily (143 patients), or VPG 90 mg twice daily (148 patients). No
      significant difference was found between the three groups in any of the
      endpoints. The rate of positive beta-human chorionic gonadotrophin per transfer
      was 38.4% with IMP, 35.0% with VPG once daily and 43.1% with VPG twice daily.
      Clinical pregnancy rate per transfer and implantation rate were 32.6% and 19.6%
      with IMP, 26.3% and 16.4% with one dose of VGP, and 37.2% and 21.1% with two
      doses of VGP. Live birth rate per transfer was 26.1%, 23.4% and 29.9%,
      respectively. Progesterone vaginal gel can be successfully used as an alternative
      to intramuscular progesterone for luteal support in IVF. One daily dose appears
      sufficient to induce clinical pregnancies and live births at a rate comparable to
      intramuscular supplementation.

PMID- 18339259
TI  - Optimal timing of ultrasonographic and Doppler evaluation of uterine receptivity
      to implantation.
AB  - In IVF programmes, transvaginal ultrasonography is used as a non-invasive method
      to evaluate uterine receptivity. The aim of this study was to determine when to
      perform this investigation in order to optimize prediction of the likelihood of
      pregnancy. Over 9 months, 124 patients undergoing IVF or intracytoplasmic sperm
      injection were studied. The ultrasonographic evaluation included endometrial
      thickness, endometrial pattern, uterine artery pulsatility index, protodiastolic
      notch, end-diastolic blood flow, and endometrial-subendometrial blood flow
      distribution pattern. All patients underwent ultrasonographic investigation on
      the days of human chorionic gonadotrophin (HCG) administration, oocyte retrieval,
      and embryo transfer. Statistical analysis was done using recursive-partitioning
      analysis. The pregnancy and implantation rates per transfer were 33 and 19.8%
      respectively. In terms of single parameters, women with an end-diastolic blood
      flow, an endometrial-subendometrial blood flow and a multilayered endometrium
      were more likely to be pregnant than women without one or more of these signs.
      The most effective combination for evaluation of uterine receptivity was end
      diastolic blood flow, endometrial pattern and endometrial thickness. Sensitivity
      and specificity of this combination were around 81%, positive predictive value
      was 68.2%, and negative predictive value 89.7%. The best sensitivity and
      specificity were obtained on the day of HCG administration: respectively 81.1 and
      81.3%.

PMID- 18339260
TI  - Health of children conceived after preimplantation genetic diagnosis: a
      preliminary outcome study.
AB  - A preliminary study was conducted on health of children conceived after
      preimplantation genetic screening and diagnosis (PGD). Forty-nine children were
      assessed with 66 matched naturally conceived (NC) controls. Primary outcome was
      neurodevelopmental screening, and secondary outcomes were evidence of other
      health problems and assessment of parent-child relationships. Study and control
      children were well matched across relevant socio-demographic variables. Growth
      parameters at mean age 18 months were normal. The mean Griffiths quotient was
      102.7 (+/-13.1) (PGD) and 103.3 (+/-12.8) (NC), both of which were within the
      normal range, and did not differ significantly. PGD cases were more likely to be
      lighter, at <2500 g (12 children, 24.5% versus one child 1.5%, P < 0.0001) and
      born earlier than controls (38.2 +/- 2.6 versus 40.0 +/- 1.4 weeks; P < 0.0001),
      consistent with other similar studies. PGD families showed no evidence of excess
      stress in their relationship with their child. The PGD group had significantly
      higher scores on the warmth-affection sub-scale (P = 0.042), and significantly
      lower scores on the aggression-hostility and rejection sub-scales (P = 0.030) of
      the questionnaire. The study showed no major ill effects from PGD on the child
      health. A larger study is needed to confirm the validity of this conclusion.

PMID- 18339261
TI  - Microchimeric fetal cells cluster at sites of tissue injury in lung decades after
      pregnancy.
AB  - Fetal cells trafficking into maternal blood during pregnancy engraft tissues and
      persist for decades in marrow and bone. While persistent fetal cells were
      initially implicated in autoimmune disease, animal studies suggest that
      microchimeric fetal cells play a broader role in response to tissue injury. This
      study investigated whether fetal cells participate in tissue repair after human
      pregnancy. Specimens were obtained from women undergoing surgery for suspected
      lung cancer. Y-fluorescence in-situ hybridization was performed on paraffin
      embedded sections, with the investigator blinded to medical histories. Male cells
      were identified in lung/thymus tissue from all women with known male pregnancies,
      but not in those without sons. The frequency of male microchimeric cells was
      seven-fold greater in lung/thymus tissues than marrow and was two-fold greater
      than normal bone from the same women. Nested-polymerase chain reaction for sex
      determining region Y confirmed male DNA in tissues. Male cells in lung were
      clustered in tumour rather than surrounding healthy tissues. In conclusion, male
      presumed-fetal cells were identified in pathological post-reproductive tissues,
      where they were more likely to be located in diseased tissues at several-fold
      higher frequency than normal tissues. It is suggested that fetal cells are
      present at sites of tissue injury and may be stem cells, either recruited from
      marrow or having proliferated locally.

PMID- 18339262
TI  - Does peer review at the US National Institutes of Health need modifying?

PMID- 18339263
TI  - Role of proteasomal activity in the induction of acrosomal exocytosis in human
      spermatozoa.
AB  - Sperm-associated proteasomes have been suggested to play an important role during
      fertilization in animals. To delineate the role of these proteasomes during
      fertilization in humans, the present study reports proteasomal proteolytic
      activity both in noncapacitated and capacitated human spermatozoa, which is not
      altered in the presence of baculovirus-expressed recombinant human zona pellucida
      glycoprotein-3 (ZP3) and zona pellucida glycoprotein-4 (ZP4). However, inhibition
      of proteasomal proteolytic activity by clasto-lactacystin beta-lactone (CLBL) and
      Z-Leu-Leu-Leu-CHO (MG132), which are specific inhibitors of the 20S proteasomal
      core proteases, led to a significant (P < 0.05) inhibition of induction of
      acrosome reaction mediated by both recombinant human ZP3 and ZP4. Both
      inhibitors, however, failed to inhibit the induction of acrosomal exocytosis
      mediated by pharmacological agonist, calcium ionophore (A23187). The binding of
      recombinant human ZP3 and ZP4, labelled with fluorescein isothiocyanate, to the
      capacitated spermatozoa was not affected in the presence of proteasomal
      inhibitors. These observations suggest a role of the sperm proteasome in the
      induction of ZP3- and ZP4-mediated acrosomal exocytosis upstream of calcium
      signalling in humans.

PMID- 18339265
TI  - Increased concentrations of the oxidative DNA adduct 7,8-dihydro-8-oxo-2
      deoxyguanosine in the germ-line of men with type 1 diabetes.
AB  - The effects of diabetes mellitus on male reproductive health have not been
      clearly defined. A previous publication from this group reported significantly
      higher levels of nuclear DNA fragmentation and mitochondrial DNA deletions in
      spermatozoa from men with type 1 diabetes. This study compared semen profiles,
      sperm DNA fragmentation and levels of oxidative DNA modification in spermatozoa
      of diabetic and non-diabetic men. Semen samples from 12 non-diabetic, fertile men
      and 11 type 1 diabetics were obtained and subjected to conventional light
      microscopic semen analysis. Nuclear DNA fragmentation was assessed using an
      alkaline Comet assay and concentrations of 7,8-dihydro-8-oxo-2-deoxyguanosine (8
      OHdG), an oxidative adduct of the purine guanosine, were assessed by high
      performance liquid chromatography. Conventional semen profiles were similar in
      both groups, whilst spermatozoa from type 1 diabetics showed significantly higher
      levels of DNA fragmentation (44% versus 27%; P < 0.05) and concentrations of 8
      OHdG (3.6 versus 2.0 molecules of 8-OHdG per 10(5) molecules of deoxyguanosine; P
      < 0.05). Furthermore, a positive correlation was observed between DNA
      fragmentation and concentrations of 8-OHdG per 10(5) molecules of deoxyguanosine
      (rs = 0.7, P < 0.05). The genomic damage evident in spermatozoa of type 1
      diabetics may have important implications for their fertility and the outcome of
      pregnancies fathered by these individuals.

PMID- 18339266
TI  - Diagnostic laparoscopy is needed after abnormal hysterosalpingography to prevent
      over-treatment with IVF.
AB  - The additional value of laparoscopy was investigated with respect to diagnosis
      and further treatment decisions after abnormal hysterosalpingography (HSG) and
      prior to intrauterine insemination (IUI). In a retrospective chart review, the
      number of patients with abnormal HSG who finally need IVF treatment based on the
      laparoscopic findings was evaluated. Independent of whether HSG showed unilateral
      or bilateral tubal pathology, IVF was the final treatment decision in only 74
      (29%) cases where laparoscopy showed bilateral abnormalities. IUI treatment was
      advised in 121 (48%) patients with laparoscopically normal findings or unilateral
      abnormalities. Fifty-seven (23%) patients were treated by IUI after receiving
      laparoscopic surgery of unilateral adhesions or endometriosis stage 1-2 or after
      ablation of moderate-severe endometriosis in a second operation. In cases of
      bilateral tubal abnormalities revealed by HSG, bilateral pathology was confirmed
      by laparoscopy in at least 58 (46%) patients and they were advised to be treated
      by IVF after laparoscopy. The agreement between abnormalities found by HSG and
      abnormalities found by laparoscopy requiring IVF treatment was poor even when HSG
      showed bilateral pathology. Based on these findings, it is concluded that
      laparoscopy is mandatory after abnormal HSG findings in the work-up prior to IUI
      to prevent over-treatment with IVF.

PMID- 18339267
TI  - Genetic alterations of HOXA10 and their effect on the severity of endometriosis
      in a Taiwanese population.
AB  - Endometriosis is one of the most common gynaecological diseases and evidence has
      suggested that it may be inherited as a complex genetic trait. HOXA10, a homeobox
      gene, is expressed in the developing uterus and participates in endometrium
      development and may contribute to endometriosis. In this study, the HOXA10 gene
      was analysed in 112 patients with endometriosis and in 54 women without
      endometriosis, as diagnosed laparoscopically. The entire HOXA10 gene was
      amplified using polymerase chain reaction followed by single-strand conformation
      polymorphism analysis and sequencing. Association between the polymorphism and
      the clinical parameters of endometriosis were examined. There were 7.23% patients
      with HOXA10 genetic alterations; however, there was no significant increase in
      the endometriosis patients compared with the controls. Most of these DNA variants
      were found to be novel mutations that reside within the HOXA10 homeobox domain.
      Six variants generate amino acid changes in the protein and one harbours a
      premature stop codon. It was found that patients with HOXA10 polymorphism were
      associated with a lower serum cancer antigen-125, a lower American Fertility
      Society score and less severe obliterated cul-de-sac. It is postulated that
      genetic alterations in the homeobox domain might lead to less specificity for
      HOXA10 protein binding to a DNA molecule.

PMID- 18339268
TI  - From embryonic stem cells to blastema and MRL mice.
AB  - New scientific knowledge offers fresh opportunities for regenerative medicine and
      tissue repair. Among various clinical options, multipotent embryonic stem cells
      (ESC) prepared from inner cell masses of rabbit blastocysts have been tested over
      many years. More recently, stem cells have been isolated from individual tissues
      and from umbilical cord blood. These methods seemingly offer similar rates of
      repair and avoid ethical complexities arising from the need for human embryos to
      prepare ESC. Different methods of regenerating tissues have now emerged, based on
      the well-known forms of organ regeneration in urodeles such as salamanders. These
      methods depend on the formation of a blastema, and recent studies on MRL mice
      have revealed that they possess similar methods of repair as in salamanders.
      There is also some evidence showing that this form of repair is also active in
      human fetuses but not in adults. Detailed knowledge of these various forms of
      tissue repair is now urgently needed in order to assess the benefits of each form
      of treatment. These matters are discussed at the end of this review where various
      investigations clarify the benefits and drawbacks of these varied approaches to
      tissue repair.

PMID- 18339270
TI  - [Improve the skills of managing syncope in children].

PMID- 18339269
TI  - Birth defects in assisted reproductive medicine.

PMID- 18339271
TI  - [Briefing of the 2007 symposium on chronic cough and recurrent respiratory tract
      infection in children].

PMID- 18339272
TI  - [A multicenter study on treatment of autonomous nerve-mediated syncope in
      children with beta-receptor blocker].
AB  - OBJECTIVE: Syncope is a common pediatric emergency. Based on an epidemiologic
      survey in the USA, around 15% of children experienced syncopal attack, which
      strongly influenced the life, study and hurt the children mentally and
      physiologically. Therefore, exploring the therapeutic regimen has become a hot
      topic in the field of pediatric cardiology. The aim of this study was to examine
      the effect of beta receptor blocker in the treatment of children with autonomous
      nerve mediated syncope. METHODS: Totally 103 children (43 males, 60 females, age
      5 - 19 yrs, median 12.0 +/- 2.6 yrs) with autonomous nerve mediated syncope from
      Beijing, Hunan, Hubei and Shanghai, were included in this study. Forty-nine of
      them suffered from vasovagal syncope (VVS) and 54 suffered from postural
      tachycardia syndrome (POTS). They were randomly divided into treatment group
      accepting oral metoprolol treatment and control group accepting oral rehydration
      salt treatment. The frequency of syncopal episodes and the outcome of head-up
      tilt (HUT) test were observed. SPSS 10.0 software was used for the statistical
      analysis of these data. RESULTS: The cure rate of children who suffered from VVS
      and POTS and took oral metoprolol was 60.61% and 68.75%, respectively, but in the
      control group, the cure rate was only 18.75% and 0.00%, respectively. The rate of
      improvement of children who suffered from VVS and POTS and were treated with oral
      metoprolol was 15.15% and 15.63%, respectively, and in the control group, it was
      6.25% and 40.91%, respectively. The effective rates for cases of VVS and POTS
      treated with oral metoprolol were higher than those of cases received oral
      rehydration salt treatment (P < 0.01). The percentage of the change from positive
      HUT to negative for children with VVS and POTS who took oral metoprolol therapy
      was 60.61% and 68.75%, respectively, but in control group, it was only 18.75% and
      9.09%, respectively (P < 0.01). There was a significant difference in the
      percentage of the change from positive HUT to negative between children with VVS
      treated with oral metoprolol and with oral rehydration salt (P < 0.01). Also, a
      significant difference was found in the percentage of the change from positive
      HUT to negative between children with POTS treated with oral metoprolol and with
      oral rehydration salt (P < 0.01). CONCLUSION: beta receptor blocker is effective
      in the treatment of children with VVS or POTS.

PMID- 18339273
TI  - [Evaluation of the development of pulmonary vessels with pulmonary venous index
      in congenital heart disease with decreased pulmonary blood flow].
AB  - OBJECTIVE: The development status of pulmonary artery is one of the most
      important criteria for decision-making strategy and predicting postoperative
      outcome in congenital heart disease with decreased pulmonary blood flow.
      Currently, Nakata index and McGoon index have been used as morphologic index in
      evaluating the development status of pulmonary artery. Those indices have some
      shortcoming. It was recently found that pulmonary veins index is a more precise
      morphological indicator of pulmonary blood flow and development status of
      pulmonary vessels. This study aimed to explore an index of evaluating pulmonary
      blood stream and the development of pulmonary vessels, as a criterion for
      surgical decision-making strategy. METHODS: The diameters of left and right
      pulmonary arteries and pulmonary veins were measured on DSA films in 74 patients
      with congenital heart disease with decreased pulmonary blood flow, The
      correlative analysis was done between Nakata index, McGoon index, pulmonary vein
      index (PVI) and postoperative outcome which were the length of stay in ICU,
      duration of mechanical ventilation and dose of inotropic drugs. RESULTS:
      Excellent correlations between the size of pulmonary veins and pulmonary arteries
      were found, the correlation between left pulmonary veins and distal portion of
      left pulmonary artery was 0.73, between left pulmonary veins and proximal portion
      of left pulmonary artery was 0.72, right pulmonary veins and distal portion of
      right pulmonary artery was 0.67, and right pulmonary veins and proximal portion
      of right pulmonary artery was 0.71. The length of stay in ICU, duration of
      mechanical ventilation and dose of inotropic drugs correlated well with PVI (r = 
      0.51, -0.478, and -0.693). Compared with Nakata index and McGoon index, PVI was a
      better criterion for evaluating the developmental status of the whole pulmonary
      vessels. In the right ventricular outlet reconstruction patients, the McGoon
      index for patients with low cardiac output syndrome (LCOS) was 1.36 +/- 0.51, and
      1.97 +/- 0.58 for patients without LCOS (t = 2.347, P < 0.05), the Nakata index
      for patients with LCOS was 164 +/- 106 mm(2)/m(2) and 269 +/- 124 mm(2)/m(2) for
      patients without LCOS (t = 2.218, P < 0.05), the PVI for patients with LCOS was
      152 +/- 77 mm(2)/m(2) and 273 +/- 125 mm(2)/m(2) for patients without LCOS (t =
      2.936, P < 0.01), pulmonary vessel index of patients with LCOS was less than that
      of those without LCOS. When PVI was < or = 180 mm(2)/m(2), postoperative
      hemodynamics was unstable, the frequency of low cardiac output syndrome and
      mortality significantly increased. CONCLUSIONS: The development of pulmonary
      arteries and pulmonary veins correlated with each other. PVI is a precise
      morphological indicator of pulmonary blood flow and development of pulmonary
      vessels. It is a helpful indicator to decide surgical strategy.

PMID- 18339274
TI  - [Effects of hemoglobin oxygenase-1 inhibitor zinc protoporphyrin IX on acute
      viral myocarditis in mice].
AB  - OBJECTIVE: To investigate the role of heme oxygenase-1 (HO-1) and its catalyst
      carbon monoxide (CO) in the development of myocardial damage and the effects of
      zinc protoporphyrin IX (ZnPPIX), an inhibitor of HO-1 on myocardium of mice with
      acute viral myocarditis. METHODS: A total of 112 inbred male Balb/C mice 4 - 6
      weeks of age were divided randomly into 3 groups: the control group (C group, n =
      32), the viral myocarditis group (V group, n = 40) and ZnPPIX group (Z group, n =
      40). The Z and V groups were inoculated intraperitoneally (i.p.) with 0.1 ml of
      10(-4.36) tissue culture infectious dose 50% (TCID(50))/ml Coxsackie virus B3
      (CVB(3)) to produce viral myocarditis model on day 0, C group was injected i.p.
      with virus-free 1640 culture culture medium 0.1 ml at the same time, then
      operation was done as follows: the mice of group C and group V were injected i.p.
      with 0.1 ml NS each day. The mice of group Z were injected i.p. with 40 micromol
      per kilogram of body weight ZnPPIX (HO-1 inhibitor) qod. Eight mice of each group
      were sacrificed on days 4, 8, 15 and 21, respectively. The blood specimens were
      collected by taking out the eyeballs to test for the content of carboxyhemoglobin
      (COHb) using spectrophotometry and cardiac troponin I (cTnI) using
      chemiluminescent immunoassay. The hearts tissue slides were also stained by
      immunohistochemistry (IHC) for HO-1 and in situ hybridization (ISH) for HO-1
      mRNA. The histological and ultrastructural changes were observed under light and
      electron microscopes. RESULTS: (1) The histopathological changes of myocardial
      cells: in the V and Z groups myocardial inflammatory cells infiltration reached
      the peak on day 8, the Z group histopathological scores were significantly lower
      than those in V group on day 8 (2.40 +/- 0.31 vs. 1.73 +/- 0.24, P < 0.01) and on
      day 15 (1.78 +/- 0.29 vs. 1.43 +/- 0.23, P < 0.05). No inflammation was present
      in group C. (2) The changes of serum cTnI level in both V and Z groups were
      significantly higher than those in C group on day 4, 8 and 15 (P < 0.01). The
      level in Z group was significantly lower than that in V group on day 4 [(6.074 +/
      1.475) ng/ml vs (7.911 +/- 1.225) ng/ml, P < 0.05] and day 8 [(0.821 +/- 0.294)
      ng/ml vs (1.480 +/- 0.454) ng/ml, P < 0.05]. (3) The changes of blood COHb level:
      compared with V group, in Z group the COHb level was lower on day 4 (P < 0.05)
      and day 15 (P < 0.01) after CVB(3) inoculation. Surprisingly, in Z group COHb
      level elevated suddenly on day 8 and showed conspicuously higher than that of V
      group (P < 0.01). (4) The result of HO-1 IHC staining: in both V and Z group
      myocardial cells had positive expression, while C group did not. (5) The results
      of HO-1 ISH were similar to those of HO-1 IHC, the A values of group Z was
      significantly lower than that of group V on day 4, 15 and 21(P < 0.01), but on
      day 8 it was higher than that of group C (P < 0.05). CONCLUSION: HO-1 inhibitor,
      ZnPP not only could inhibit HO-1 overexpression but also could induce HO-1
      expression temporarily and protect against myocardial injury at the early stage
      of acute viral myocarditis.

PMID- 18339275
TI  - [The present status and progress in application of pulmonary artery stents].

PMID- 18339276
TI  - [Survivin and pulmonary hypertension].

PMID- 18339277
TI  - [Paroxysmal nonepileptic abnormal movement during sleep in children].

PMID- 18339278
TI  - [Detection of subtelomeric rearrangements in patients with idiopathic mental
      retardation/developmental delay].
AB  - OBJECTIVE: To detect subtelomeric rearrangement in patients with idiopathic
      mental retardation/developmental delays (MR/DD) and to provide new methods and
      evidence for the etiologic diagnosis of MR/DD in China. METHODS: 1. INCLUSION
      CRITERIA: (1) Moderate to severe MR/DD; (2) no definite perinatal brain injury;
      (3) no toxication, hypoxia, infection of central nervous system and cranial
      trauma; (4) routine karyotyping is normal; (5) no evidence of typical inherited
      metabolic disorder or specific neurodegenerative disorders from cranial neuro
      imaging and blood/urinary metabolic diseases screening; (6) no mutation of FMR1
      gene in male patients plus one of the following criteria: (1) positive family
      history of MR; (2) positive family history of miscarriages and perinatal deaths;
      (3) abnormal growth; (4) facial and non-facial dysmorphism. 2. Multiplex ligation
      dependent probe amplification (MLPA) and fluorescence in situ hybridization
      (FISH) were applied to detect subtelomeric rearrangements in patients and their
      parents. RESULTS: Four cases were identified from 39 selected cases with
      subtelomeric rearrangements (10%), including der (2) t (2; 4) (pter; pter),
      11qter del, 8pter del, and 15p11.2 del. The first two abnormalities of chromosome
      subtelomeric regions have not been reported yet. All these cases had some small
      dysmorphologies, such as microcephaly, hypertelorism, low nasal bridge, and three
      of them had hypotonia. One case had recurrent seizure and abnormal behavior
      (laughter not associated with happiness), and another case with dysgenesis of
      corpus callosum and septum pellucidum. Family and perinatal histories were normal
      for all cases. All chromosome rearrangements were de novo which were not from the
      parents with normal phenotype. It indicated that all these abnormal
      rearrangements should be responsible for the mental retardation phenotype of
      these patients. The phenotype of case 4 was similar to Angelman syndrome, his
      deletion was actually a kind of interstitial rearrangements. It will be confirmed
      by DNA methylation test to determine whether the deleted allele was of maternal
      origin. CONCLUSIONS: The subtelomeric rearrangements were found in 10% patients
      with idiopathic MR. It indicated that subtelomeric rearrangements should be one
      of major reasons of MR/DD related to genetic factors. Two novel subtelomeric
      rearrangements were identified. These de novo rearrangements are probably disease
      related, because they are not inherited from their parents with normal phenotype.
      The detection should be carried out for all the patients with idiopathic MR/DD
      with unknown origin, because one cannot figure out the specific signs for
      subtelomeric rearrangements. Sequentially use of MLPA and FISH is a more
      efficient and economic method to detect the subtelomeric rearrangements.

PMID- 18339279
TI  - [Clinical and genetic analysis of a family with Pelizaeus-Merzbacher disease].
AB  - OBJECTIVE: Pelizaeus-Merzbacher disease (PMD) is a rare X-linked recessive
      leukoencephalopathy. Few reports of PMD patients without genetic confirmation
      have been published in the mainland of China. The clinical and genetic features
      of a family with PMD were analyzed, which may contribute to definite diagnosis,
      genetic counseling and prenatal diagnosis of this rare hereditary disease in
      China. METHODS: Clinical data of the proband and other family members as well as
      14 DNA samples were collected. Clinical features including symptoms, signs and
      cranial MRI were analyzed. Multiplex ligation-dependent probe amplification
      (MLPA) assays were performed to detect PLP1 duplication, which helps identify the
      type of PLP1 mutation in this family and the genotype-phenotype correlations.
      RESULTS: (1) The proband and the other 3 male patients in the family presented
      with nystagmus, motor retardation followed by regression. The cranial MRI of
      proband showed evidence of poor myelination with diffused high signal in white
      matter region on T2-weighed image and reduced amount of white matter in volume,
      which is consistent with the typical features of cranial MRI in PMD. (2)
      PLP1duplication was identified in the proband. Combined with the clinical
      features of the proband and other patients in this family, the diagnosis of
      classic form of PMD was confirmed. Another 3 females with normal phenotype in the
      family were proved to be carriers of PLP1duplication. CONCLUSIONS: (1) The
      Classic form of PMD in this pedigree is resulted from the PLP1 duplication, which
      is consistent with the previously reported genotype-phenotype correlations; (2)
      The results serve as an evidence for reliable genetic counseling and prenatal
      diagnosis for this family. (3) MLPA, which is a newly developed method, is a
      rapid and reliable technique to detect the whole gene duplication of PLP1.

PMID- 18339280
TI  - [Non-invasive prenatal genetic diagnosis of beta-thalassaemia using single fetal
      nucleated erythrocyte from maternal blood].
AB  - OBJECTIVE: To investigate non-invasive prenatal genetic diagnosis of beta
      thalassaemia using a single fetal nucleated erythrocyte (NRBC) from maternal
      blood by comparing with the genotype obtained from chorionic villus or
      amniocytes, and to evaluate the diagnostic results in reliability and feasibility
      of this method. METHODS: Maternal blood samples were obtained from 28 pregnant
      women at risk of beta thalassaemia during 9 - 34 weeks of gestation. NRBCs in
      maternal blood were enriched by single density gradient separation, stained with
      benzidine, and then collected by micromanipulation individually. After primer
      extension preamplification (PEP) of the entire genome from each single NRBC,
      short tandem repeat (STR) genotype was analyzed after further amplification of
      this gene. Single NRBC was tested individually to identify if it was fetal or
      maternal in origin by STR genotype of NRBC and its corresponding parents. beta
      globin DNA fragments were amplified with nested-PCR using PEP product of a single
      fetal NRBC that was determined to be fetal in origin. Fetal beta-globin genotypes
      were analyzed by reverse dot-blot hybridization (RDB), the accuracy was evaluated
      by comparing with genotype which had been determined on DNA obtained from
      chorionic villus (CVS) or amniocytes. RESULTS: A total of 298 NRBCs were found in
      all of 28 pregnant women at a range of 4 to 13 per 5 ml venous blood. After PEP,
      about 43.6% of NRBCs were determined to be fetal in origin by STR typing. Using
      PEP product of a single fetal NRBC as template, beta-globin DNA fragment was
      examined on agarose gel after nested-PCR, amplification efficiency was 90.8%
      (118/130). Fetal beta-globin genotypes were achieved successfully in all cases
      with RDB. Comparing with the genotypes which were obtained from CVS or
      amniocytes, the rate of diagnostic accuracy was 85.7% (24/28). CONCLUSIONS: PEP
      technique and STR genotype analysis provide effective method for identification
      of single nucleated erythrocyte from maternal blood in origin. With the
      techniques PEP and RDB, fetal beta-globin genetic diagnosis was achieved using a
      single fetal NRBC from maternal blood. The method had a high accuracy and
      reliability in diagnosis. It may become an optional approach to non-invasive
      prenatal diagnosis of beta-thalassemia.

PMID- 18339281
TI  - [Sputamentum leading to pulmonary atelectasis, mediastinal emphysema and
      pneumoderma in a child].

PMID- 18339282
TI  - [Effect of FTY720 on glomerulosclerosis and expression of cell cycle regulatory
      proteins in subtotally nephrectomized rats].
AB  - OBJECTIVE: To study the effect of FTY720 on glomerulosclerosis and expression of
      cell cycle regulatory proteins in subtotal nephrectomized rats. METHODS: Twenty
      four rats were divided into sham-operation group, glomerulosclerosis model group
      and FTY720 treated glomerulosclerosis group with 8 rats in each group. The rats
      in the latter two groups were subjected to subtotal nephrectomy. After operation,
      the FTY720 treated group was fed with FTY720 at a dose of 0.5 mg/(kg x d) for 12
      weeks. Urine protein excretion was measured before operation and 2 w, 4 w, 8 w
      and 12 w after operation. Then the rats were sacrificed and the left kidney was
      subjected to pathological evaluation. The expression of collagen IV, fibronectin,
      and cyclin E, p21, p27 were determined by immunohistochemical methods. RESULTS:
      Compared with the control group, the model group showed higher daily urine
      protein (Up) excretion from 2 w, (8.07 +/- 1.61) mg/d and thereafter. At 12 w, Up
      increased to (28.60 +/- 12.21) mg/d in model group, significantly higher than
      that in control group (P < 0.05). After treatment with FTY720, Up began to
      decrease from 4 w after operation, (9.90 +/- 1.49) mg/d at that time and (11.35
      +/- 2.09) mg/d at 12 w, both were significantly lower than those in model group
      (P < 0.01). The model group showed higher level of serum creatinine from 8 w,
      (61.08 +/- 4.28) micromol/L at that time, (130.20 +/- 23.90) micromol/L at 12 w,
      both were much higher than those in control group (P < 0.05). In FTY720 treated
      group, serum creatinine level was (80.19 +/- 7.11) micromol/L at 12 w, much lower
      than that in model group. The changes of BUN were similar to those of creatinine
      in each group. Renal pathology and immunohistological evaluation showed that
      FTY720 could significantly inhibit the expression of collagen-IV and fibronectin
      in glomeruli and attenuate the extent of glomerulosclerosis. Moreover, FTY720
      could upregulate glomerular expression of p21 and downregulate glomerular
      expression of p27 and cyclin E. The expression levels of p21 and cyclin E were
      significantly lower in treatment group than in model group (P < 0.05), but still
      higher than those in control group (P < 0.05). p27 expression in glomeruli was
      stronger in treatment group than that in model group (P < 0.05), and lower than
      that in normal group but the difference was not significant. CONCLUSION: FTY720
      can diminish urine protein excretion and prevent glomerulosclerosis in subtotally
      nephrectomized rats. This protective effect is presumed to be associated with its
      effect on expression of cell cycle regulatory proteins, and inhibition of
      extracellular matrix accumulation in glomeruli.

PMID- 18339283
TI  - [Analysis on variance of common pathogenic bacteria and drug resistance in
      children in Chengdu area from 2001 to 2006].
AB  - OBJECTIVE: To investigate the variance and drug resistance of pathogenic bacteria
      isolated from children with infectious diseases seen between 2001 and 2006 in
      Chengdu area. METHODS: A total of 2888 pathogenic bacterial strains isolated from
      children in Chengdu Children's Hospital from 2001 to 2006 were analyzed. Tests
      were performed according to the guidelines of National Committee for Clinical
      Laboratory Standards (NCCLS) of the United States. RESULT: (1) Of the 2888
      strains, 1845 (63.9%) were Gram negative bacteria. The main pathogenic bacteria
      included Escherichia coli (Ec, 718 strain, 24.9%), Hemophilus (H, 476 strain,
      16.5%), Streptococcus pneumoniae (Sp, 412 strain, 14.3%), Klebsiella pneumoniae
      (Kp, 369 strain, 12.8%), Staphylococcus aureus (Sa, 353 strain, 12.2%),
      Staphylococcus epidermidis (Se, 278 strain, 9.6%), Pseudomonas aeruginosa (Pa,
      146 strain, 5.1%) and other non-zymocyte (Onz, 136 strain, 4.7%). (2) The common
      pathogens found in blood specimen were 158 strain, which included Se (78 strain,
      49.4%), Ec (23 strain, 14.6%), Kp (17 strain, 10.8%), Sa (14 strain, 8.9%), Onz
      (14 strain, 8.9%), Sp (7 strain, 4.4%) and Pa (5 strain, 3.2%). (3) The number of
      common pathogens isolated from patients with lower respiratory tract infection
      was 2018, including Ec (441 strains, 21.9%), H (430 strains, 21.3%), Sp (368
      strains, 18.2%), Kp (253 strains, 12.5%), Sa (207 strains, 10.3%), Se (149
      strains, 7.3%), Pa (97 strains, 4.8%) and Onz (73 strains, 3.6%). (4) There were
      120 strains of common pathogens isolated from urine specimens, including Ec (78
      strains, 65%), Kp (25 strains, 20.8%), Onz (7 strains, 5.8%), Pa (5 strains,
      4.2%) and Se (5 strains, 4.2%). (5) There were 497 strains of common pathogens
      found in pus specimens, including Ec 167 strains, (33.6%), Sa (126 strains,
      25.4%), Se (46 strains, 9.3%), H (44 strains, 8.9%), Onz (37 stains, 7.4%), Kp
      (31 strains, 6.2%), Sp (26 strains, 5.2%) and Pa (20 strain, 4.0%). The trend of
      drug resistance of pathogenic bacteria to antibiotics deteriorated. The
      proportion of methicillin-resistant Staphylococcus aureus (MRSA) was 6.7% and the
      methicillin-resistant coagulase-negative Staphylococci (MRCNS) rate was 20% in
      2001 - 2003. The total proportion of extended-spectrum beta-lactamase stains
      (ESBL(S)) in Ec and Kp was 21.8%, and the rate of beta-lactamase production
      stains of Hemophilus influenzae (Hi) was 19.4% in 2001 - 2003.The proportion of
      MRSA was 17.2% and the MRCNS rate was 70.2%, the total proportion of ESBL(S) in
      Ec and Kp was 43.8%, and the rate of beta-lactamase producing stains of Hi was
      39.7% in 2004 - 2006. CONCLUSION: The distribution of common pathogenic bacteria
      seen in Chengdu Children's Hospital has changed and the trend of drug resistance
      of pathogenic bacteria to antibiotics deteriorated in recent three years.
      Regionally monitoring the changes in pathogenic bacteria and the trend of drug
      resistance to antibiotics is paramount in guiding the pediatric clinical
      treatment.

PMID- 18339284
TI  - [Values of tandem mass spectrometry in etiologic diagnosis of cerebral
      developmental retardation].
AB  - OBJECTIVES: To investigate the values of tandem mass spectrometry (MS/MS) in
      etiologic diagnosis and understanding therapeutic effect in cerebral
      developmental retardation, and to help patients in early diagnosis, treatment and
      favorable prognosis. METHODS: One hundred and fifty-eight childhood patients with
      brain heteroplasia were tested from July 2004 to October 2006. The blood was
      collected on filter paper, punched and extracted into methanol solution with
      stable isotope labeled internal standards, then derivatized with butanolic-HCl.
      After preparation, the samples were analysed by tandem mass spectrometry. Eleven
      MS/MS-positive patients were further analyzed based on gas chromatography/mass
      spectrometry (GC/MS) analysis of urine, clinical course, and treatment outcome.
      RESULTS: Eleven of 158 patients (7.0%) with inborn metabolic error were
      confirmed, including five with methylmalonic acidemia, two with propionic
      acidemia, one with ornithine transcarbamylase deficiency, one with maple syrup
      urine disease, one with phenylketonuria, and one with biotinidase deficiency.
      Among them, five were male, six were female, aged from 4 days to 21 months. The
      clinical manifestations were diverse, including mental developmental retardation
      or degradation (11 cases), convulsion (5 cases), coma (4 cases), vomiting (4
      cases), malnutrition (4 cases), lethargy (3 cases), repeated infection (3 cases),
      hypotonia (2 cases), etc. Laboratory findings showed metabolic acidosis,
      hyperammonemia, hyperlactacidemia, anemia, etc. MRI findings of the brain showed
      cerebral atrophy, a pattern of bilateral T(2)W high signal intensity or/and T(1)W
      low signal intensity in cerebral white matter and multiple encephalomalacia or
      vesicular change, ect. In methylmalonic acidemia patients, the early onset with
      severe acidosis and coma have had a poor prognosis. Improvement was observed in 8
      cases after treatment with vitamin B(12), L-carnitine, special milk, low-protein
      diet or biotin, etc. However 3 MMA patients died. CONCLUSION: MS/MS was helpful
      for some patients in etiologic diagnosis and understanding therapeutic effect of
      cerebral developmental retardation. Early diagnosis and appropriate treatment are
      essential to improve the prognosis and prevent brain damage.

PMID- 18339285
TI  - [Identification of a novel missense mutation of the DAX-1 gene in a Chinese
      pedigree with X-linked adrenal hypoplasia congenita].
AB  - OBJECTIVE: Inactivating mutations of DAX-1 give rise to the X-linked form of
      adrenal hypoplasia congenita (AHC). Affected individuals are at risk of early
      postnatal Addisonian crisis, but the variable phenotypic expression of DAX-1
      insufficiency renders this diagnosis challenging. This study aimed to understand
      the clinical features and identify DAX-1 gene mutation of the affected
      individuals and their relatives in a Chinese adrenal hypoplasia congenita
      kindred. METHODS: The proband was diagnosed as adrenal insufficiency shortly
      after birth and his elder cousin was also diagnosed as having this disease at the
      age of about 8 years. Clinical data were obtained from 2 affected individuals
      when they were hospitalized into the department of pediatrics, Ruijin Hospital in
      2006; 20 peripheral blood samples were obtained from the affected individuals and
      their relatives; exons in DAX-1 gene were amplified, and PCR product was purified
      and sequenced directly for analyzing mutation. RESULTS: A novel hemizygous
      mutation (T785C) was found in DAX-1 gene in both patients. Some clinical features
      such as the age of onset were different although these 2 patients carried the
      same mutation. There were 5 carriers of this mutation in the patients' maternal
      pedigree. CONCLUSION: The results suggested that adrenal hypoplasia congenita in
      this kindred was caused by a novel mutation (T785C) in DAX-1 gene, and the same
      mutation can give rise to the variable phenotype.

PMID- 18339286
TI  - [Language development norms for infants in Shanghai].

PMID- 18339287
TI  - [Sepsis in children with pneumonia: a retrospective analysis].

PMID- 18339288
TI  - [Periventricular occlusion of muscular ventricular septal defects under the
      guidance of transesophageal echocardiography].

PMID- 18339289
TI  - [Changes of Th1/Th2 lymphocyte subset and red blood cell immunity in children
      with congenital heart disease].

PMID- 18339290
TI  - [Primary anaplastic large cell lymphoma originated from lung in a case].

PMID- 18339291
TI  - [A case of von Willebrand disease type 3 misdiagnosed as hemophilia A].

PMID- 18339292
TI  - [Prenatal diagnosis of congenital adrenal hyperplasia in a case].

PMID- 18339293
TI  - [A case of heart valve involvement in pediatric systemic lupus erythematosus].

PMID- 18339294
TI  - [Clinical and biopsy hepatocyte ultrastructural observation of Dubin-Johnson
      syndrome in sib sisters].

PMID- 18339295
TI  - [Review of early feeding of infants].

PMID- 18339296
TI  - [Summit on the early nutrition of infants].

PMID- 18339298
TI  - The cytoplasmic plaque of tight junctions: a scaffolding and signalling center.
AB  - The region of cytoplasm underlying the tight junction (TJ) contains several
      multimolecular protein complexes, which are involved in scaffolding of membrane
      proteins, regulation of cytoskeletal organization, establishment of polarity, and
      signalling to and from the nucleus. In this review, we summarize some of the most
      recent advances in understanding the identity of these proteins, their domain
      organization, their protein interactions, and their functions in vertebrate
      organisms. Analysis of knockdown and knockout model systems shows that several TJ
      proteins are essential for the formation of epithelial tissues and early
      embryonic development, whereas others appear to have redundant functions.

PMID- 18339299
TI  - Tight junction biogenesis during early development.
AB  - The tight junction (TJ) is an essential component of the differentiated
      epithelial cell required for polarised transport and intercellular integrity and
      signalling. Whilst much can be learnt about how the TJ is constructed and
      maintained and how it functions using a wide range of cellular systems, the
      mechanisms of TJ biogenesis within developmental models must be studied to gain
      insight into this process as an integral part of epithelial differentiation.
      Here, we review TJ biogenesis in the early mammalian embryo, mainly considering
      the mouse but also including the human and other species, and, briefly, within
      the amphibian embryo. We relate TJ biogenesis to inherent mechanisms of cell
      differentiation and biosynthesis occurring during cleavage of the egg and the
      formation of the first epithelium. We also evaluate a wide range of exogenous
      cues, including cell-cell interactions, protein kinase C signalling, gap
      junctional communication, Na+/K+-ATPase and cellular energy status, that may
      contribute to TJ biogenesis in the embryo and how these may shape the pattern of
      early morphogenesis.

PMID- 18339300
TI  - Simultaneous immunochemical detection of stanozolol and the main human
      metabolite, 3'-hydroxy-stanozolol, in urine and serum samples.
AB  - Two enzyme-linked immunosorbent assays (ELISAs) have been established for the
      analysis of stanozolol (St) and 3'-hydroxy-stanozolol (3'OH-St), the main
      metabolite found in humans. The immunizing hapten N2'-(5-valeric acid)-androst-2
      eno[3,2-c]-pyrazol-17a-methyl-17b-ol (hapten 8) has been designed with the aid of
      molecular modeling and theoretical tools to allow immunochemical detection of
      both compounds. Using an ELISA based on a homologous antisera/coating antigen
      combination, St can be selectively quantified without significant interference of
      the St metabolites or other steroids potentially present in the biological
      samples. On the other hand, St immunoreactivity equivalents due to the additional
      presence of 3'OH-St can also be quantified using an ELISA based on a heterologous
      antisera/coating antigen combination, in which the metabolite can be detected
      with 51% cross-reactivity. Thus, As147/5BSA detects 3'OH-St and St in buffer with
      IC(50) values of 1.46 and 0.68 microg L(-1), respectively. In contrast,
      As147/8BSA is highly specific for St with an IC(50) of 0.16 microg L(-1) and a
      limit of dection of just 0.022 microg L(-1). Performance of both assays in urine
      and serum samples has been evaluated and demonstrate that inappropriate use of
      stanozolol by athletes or young people can be detected in these matrices after
      simple cleanup methods, with IC(50) values below the minimum performance required
      levels established by the World Antidoping Agency.

PMID- 18339301
TI  - Effect of acylation on the interaction of the N-Terminal segment of pulmonary
      surfactant protein SP-C with phospholipid membranes.
AB  - SP-C, the smallest pulmonary surfactant protein, is required for the formation
      and stability of surface-active films at the air-liquid interface in the lung.
      The protein consists of a hydrophobic transmembrane alpha-helix and a cationic N
      terminal segment containing palmitoylated cysteines. Recent evidence suggests
      that the N-terminal segment is of critical importance for SP-C function. In the
      present work, the role of palmitoylation in modulating the lipid-protein
      interactions of the N-terminal segment of SP-C has been studied by analyzing the
      effect of palmitoylated and non-palmitoylated synthetic peptides designed to
      mimic the N-terminal segment on the dynamic properties of phospholipid bilayers,
      recorded by spin-label electron spin resonance (ESR) spectroscopy. Both
      palmitoylated and non-palmitoylated peptides decrease the mobility of
      phosphatidylcholine (5-PCSL) and phosphatidylglycerol (5-PGSL) spin probes in
      dipalmitoylphosphatidylcholine (DPPC) or dipalmitoylphosphatidylglycerol (DPPG)
      bilayers. In zwitterionic DPPC membranes, both peptides have a greater effect at
      temperatures below than above the main gel-to-liquid-crystalline phase
      transition, the palmitoylated peptide inducing greater immobilisation of the
      lipid than does the non-palmitoylated form. In anionic DPPG membranes, both
      palmitoylated and non-palmitoylated peptides have similar immobilizing effects,
      probably dominated by electrostatic interactions. Both palmitoylated and non
      palmitoylated peptides have effects comparable to whole native SP-C, as regards
      improving the gel phase solubility of phospholipid spin probes and increasing the
      polarity of the bilayer surface monitored by pK shifts of fatty acid spin probes.
      This indicates that a significant part of the perturbing properties of SP-C in
      phospholipid bilayers is mediated by interactions of the N-terminal segment. The
      effect of SP-C N-terminal peptides on the chain flexibility gradient of DPPC and
      DPPG bilayers is consistent with the existence of a peptide-promoted
      interdigitated phase at temperatures below the main gel-to-liquid-crystalline
      phase transition. The palmitoylated peptide, but not the non-palmitoylated
      version, is able to stably segregate interdigitated and non-interdigitated
      populations of phospholipids in DPPC bilayers. This feature suggests that the
      palmitoylated N-terminal segment stabilizes ordered domains such as those
      containing interdigitated lipids. We propose that palmitoylation may be important
      to promote and facilitate association of SP-C and SP-C-containing membranes with
      ordered lipid structures such as those potentially existing in highly compressed
      states of the interfacial surfactant film.

PMID- 18339302
TI  - Calcium influx into phospholipid vesicles caused by dynorphin neuropeptides.
AB  - Dynorphins, endogeneous opioid peptides, function as ligands to the opioid kappa
      receptors but also induce non-opioid excitotoxic effects. Dynorphin A can
      increase the intra-neuronal calcium concentration through a non-opioid and non
      NMDA mechanism. In this investigation, we show that big dynorphin, dynorphin A
      and to some extent dynorphin A (1-13), but not dynorphin B, allow calcium to
      enter into large unilamellar phospholipid vesicles with partly negative
      headgroups. The effects parallel the previously studied potency of dynorphins to
      translocate through biological membranes and to cause calcein leakage from large
      unilamellar phospholipid vesicles. There is no calcium ion influx into vesicles
      with zwitterionic headgroups. We have also investigated if the dynorphins can
      translocate through the vesicle membranes and estimated the relative strength of
      interaction of the peptides with the vesicles by fluorescence resonance energy
      transfer. The results show that dynorphins do not translocate in this membrane
      model system. There is a strong electrostatic contribution to the interaction of
      the peptides with the membrane model system.

PMID- 18339303
TI  - Gramicidin A-based peptide vector for intracellular protein delivery.
AB  - The development of the peptide-based vectors for the intracellular delivery of
      biologically active macromolecules has opened new prospects of their application
      in research and therapy. Earlier the amphipathic cell-penetrating peptide (CPP)
      Pep-1 was reported to mediate cellular uptake of proteins without covalent
      binding to them. In this work we studied the ability of a series of membrane
      active amphipathic peptides, based on the gramicidin A sequence, to transport a
      model protein across the eukaryotic cell membrane. Among them the positively
      charged Cys-containing peptide P10C demonstrated the most effective beta
      galactosidase intracellular delivery. Besides, this peptide was shown to form
      noncovalent associates with beta-galactosidase as judged from electrophoresis and
      enzymatic activity assays. In addition, a series of new gramicidin analogues were
      prepared and the effect of N-terminus modification of gramicidin on the protein
      transduction efficiency was studied.

PMID- 18339304
TI  - Inhibition of osteocyte apoptosis by fluid flow is mediated by nitric oxide.
AB  - Bone unloading results in osteocyte apoptosis, which attracts osteoclasts leading
      to bone loss. Loading of bone drives fluid flow over osteocytes which respond by
      releasing signaling molecules, like nitric oxide (NO), that inhibit osteocyte
      apoptosis and alter osteoblast and osteoclast activity thereby preventing bone
      loss. However, which apoptosis-related genes are modulated by loading is unknown.
      We studied apoptosis-related gene expression in response to pulsating fluid flow
      (PFF) in osteocytes, osteoblasts, and fibroblasts, and whether this is mediated
      by loading-induced NO production. PFF (0.7+/-0.3Pa, 5Hz, 1h) upregulated Bcl-2
      and downregulated caspase-3 expression in osteocytes. l-NAME attenuated this
      effect. In osteocytes PFF did not affect p53 and c-Jun, but l-NAME upregulated c
      Jun expression. In osteoblasts and fibroblasts PFF upregulated c-Jun, but not Bcl
      2, caspase-3, and p53 expression. This suggests that PFF inhibits osteocyte
      apoptosis via alterations in Bcl-2 and caspase-3 gene expression, which is at
      least partially regulated by NO.

PMID- 18339305
TI  - IL-15 inhibits pre-B cell proliferation by selectively expanding Mac-1+B220+ NK
      cells.
AB  - Natural killer (NK) cells are the cells critical for inhibition of repopulation
      of allogenic bone marrow cells. However, it is not well known if NK cells affect
      autologous lymphopoiesis. Here, we observed that NK cells could inhibit pre-B
      cell proliferation in vitro driven by interleukin (IL)-7 in a manner dependent on
      IL-15. Interestingly, the great majority of expanding NK cells were Mac
      1(+)B220(+), a recently identified potent interferon (IFN)-gamma producer.
      Indeed, IFN-gamma was produced in those cultures, and pre-B cells lacking IFN
      gamma receptors, but not those lacking type I IFN receptors, were resistant to
      such an inhibition. Furthermore, even NK cells from mice lacking beta2
      microglobulin, which were known to be functionally dampened, inhibited pre-B cell
      proliferation as well. Thus, activated NK cells, which were expanded selectively
      by IL-15, could potentially regulate B lymphopoiesis through IFN-gamma beyond the
      selection imposed upon self-recognition.

PMID- 18339306
TI  - Regulation of pancreatic duct cell differentiation by phosphatidylinositol-3
      kinase.
AB  - We have previously demonstrated that the phosphatidylinositol-3 kinase (PI3K)/Akt
      signaling is essential for pancreatic regeneration after partial pancreatectomy
      in mice. In the present study, we examined a role of PI3K/Akt signaling for
      pancreatic duct cell differentiation into insulin-producing cells. Epithelial
      like cells were isolated from mouse pancreas and confirmed to be positive for a
      duct cell marker cytokeratin-20 (CK-20) but negative for insulin. Incubation of
      these cells with epidermal growth factor, exhibited a gradual increase in Akt
      phosphorylation and expression of pancreatic duodenal homeobox-1 (PDX-1), a
      regulator of beta-cell differentiation. Three weeks later, these CK-20-positive
      cells were noted to express insulin as determined by immunofluorescent double
      staining. Akt phosphorylation, PDX-1 expression, and insulin production were
      effectively reduced by blocking the PI3K/Akt pathway using siRNA to the p85alpha
      regulatory subunit of PI3K. Our results demonstrate that PI3K/Akt activation has
      a critical role for pancreatic duct cell differentiation into insulin-producing
      cells.

PMID- 18339307
TI  - Clinical and genetic characterization of Chanarin-Dorfman syndrome.
AB  - We describe the clinical features, muscle pathology features, and molecular
      studies of seven patients with Chanarin-Dorfman syndrome (CDS) or neutral lipid
      storage disease and ichthyosis (NLSDI), a multisystem triglyceride storage
      disease with massive accumulation of lipid droplets in muscle fibers. All
      patients presented with congenital ichthyosiform erythroderma, cytoplasmic lipid
      droplets in blood cells, mild to severe hepatomegaly, and increased serum CK
      levels and liver enzymes. Three patients showed muscle symptoms and three had
      steathorrea. Molecular analysis identified five mutations, three of which are
      novel. These findings expand the clinical and mutational spectrum and underline
      the genetic heterogeneity of this disease.

PMID- 18339308
TI  - A new EAE model of brain demyelination induced by intracerebroventricular
      pertussis toxin.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a primary animal model of
      multiple sclerosis (MS). MS predominantly presents with evidence of lesions in
      the subcortical periventricular white matter regions of the brain. Research into
      the pathogenesis of the demyelinating lesions in the brain has been hampered by
      the fact that conventional models of EAE present with progressive ascending
      paralysis which recapitulates mainly the spinal cord lesions of multiple
      sclerosis. There is little evidence of brain involvement. Systemic administration
      of pertussis toxin (PTx) has been shown to induce the proinflammatory cascade of
      TGF-beta, IL-6, and Th17 in the central nervous system, which recently has been
      identified as essential in the development of EAE. To determine whether
      intracerebroventricular (icv) administration of PTx would result in subcortical
      periventricular demyelinating lesions in the brain, we examined the effect in a
      MOG induced EAE model. We found that icv PTx induced subcortical periventricular
      brain lesions that resemble the pathologic demyelinating lesions of MS. Moreover,
      icv PTx induced Th17 infiltration and increased expression of cytokines IL-6 and
      TGF-beta. We thus generated a highly reproducible model with remarkable
      histological similarities to the predominant demyelinating brain lesions seen in
      MS.

PMID- 18339309
TI  - The role of mitochondrial glycerol-3-phosphate acyltransferase-1 in regulating
      lipid and glucose homeostasis in high-fat diet fed mice.
AB  - Glycerol-3-phosphate acyltransferase (GPAT) is involved in triacylglycerol (TAG)
      and phospholipid synthesis, catalyzing the first committed step. In order to
      further investigate the in vivo importance of the dominating mitochondrial
      variant, GPAT1, a novel GPAT1(-/-) mouse model was generated and studied. Female
      GPAT1(-/-) mice had reduced body weight-gain and adiposity when fed chow diet
      compared with littermate wild-type controls. Furthermore, GPAT1(-/-) females on
      chow diet showed decreased liver TAG content, plasma cholesterol and TAG levels
      and increased ex vivo liver fatty acid oxidation and plasma ketone bodies.
      However, these beneficial effects were abolished and the glucose tolerance tended
      to be impaired when GPAT1(-/-) females were fed a long-term high-fat diet (HFD).
      GPAT1-deficiency was not associated with altered whole body energy expenditure or
      respiratory exchange ratio. In addition, there were no changes in male GPAT1(-/-)
      mice fed either diet except for increased plasma ketone bodies on chow diet,
      indicating a gender-specific phenotype. Thus, GPAT1-deficiency does not protect
      against HFD-induced obesity, hepatic steatosis or whole body glucose intolerance.

PMID- 18339310
TI  - Cell cycle dependent telomere regulation by telomerase in human bone marrow
      mesenchymal stem cells.
AB  - Human bone marrow mesenchymal stem cells (hMSCs) are a promising source for
      clinical stem cell transplantation. However, telomere regulation mechanisms, as
      one of the possible major mechanisms by which hMSCs sustain their stem cell
      characteristics, remain unknown. We isolated hMSCs by plastic adhesion and
      characterized these cells by morphology, immune phenotype and differentiation
      capacity. Telomerase was found negative in hMSCs, but slightly up-regulated in
      hMSC-derived adipocytes by the Telomeric Repeat Amplification Protocol (TRAP)
      assay. Moreover, hMSCs lack the alternative lengthening of telomeres (ALT)
      mechanism, because the hallmarks of ALT, such as very long and heterogeneous
      telomeres, extra-chromosome telomere repeat DNA (ECTR), and ALT-associated
      promyelocytic leukemia bodies (APBs), were not evident. However, when hMSCs were
      arrested in S phase with a combination of serum deprivation and aphidicolin,
      previously undetectable telomerase activity became predominantly positive.
      Meanwhile, the expression level of hTERT protein and mRNA increased, paralleled
      with the appearance of a large cohort of synchronized hMSCs at S phase. These
      findings provide a profile of telomere regulation by cell cycle dependent
      expression of telomerase in hMSCs and may lead to a better understanding of the
      stem cell nature of these cells.

PMID- 18339311
TI  - TRPM6 expression and cell proliferation are up-regulated by phosphorylation of
      ERK1/2 in renal epithelial cells.
AB  - Transient receptor potential melastatin 6 (TRPM6) is a magnesium channel and
      expressed in the intestine and renal distal tubules. Little is known about the
      regulatory mechanism of TRPM6 expression and the role of magnesium influx. EGF
      increased the phosphorylation of ERK1/2 and TRPM6 expression that were inhibited
      by U0126 in renal epithelial NRK-52E cells. Furthermore, EGF enhanced the influx
      of magnesium, whereas U0126 and TRPM6 siRNA inhibited it. EGF increased the
      proportion of cells in S phase, whereas U0126 and TRPM6 siRNA increased the
      proportion in G1 phase. The phosphorylation of ERK1/2 may up-regulate TRPM6
      expression and magnesium influx, resulting in an increase in cell proliferation
      with a shift from G1 to S phase.

PMID- 18339312
TI  - Extraction, isolation and NMR data of the tetraether lipid
      calditoglycerocaldarchaeol (GDNT) from Sulfolobus metallicus harvested from a
      bioleaching reactor.
AB  - The successful extraction and isolation of the hydrolysed tetraether lipid
      calditoglycerocaldarchaeol (GDNT) from Sulfolobus metallicus, a key thermophilic
      bioleaching archaeon, is described. The archaeal biomass was recovered directly
      from a thermophilic (68 degrees C) bioleaching tank reactor used to extract
      nickel from a pentlandite mineral concentrate. The initial Soxhlet extraction
      method employed was scaled to a bench-scale extraction procedure suitable for the
      preparation of gram-scale quantities of GDNT. The GDNT so obtained was analysed
      by 1D- and 2D-NMR techniques, providing the first complete 13C and 2D-NMR data
      set for GDNT, including that for the intact underivatised calditol moiety. The
      study demonstrates the feasibility of recovering high-quality GNDT from
      thermophilic archaeal-mediated bioleaching reactors. The recovery of these lipids
      at relatively low cost, as a by-product from bioleaching reactors used in the
      metals processing industry, has important implications for future tetraether
      lipid availability and costs.

PMID- 18339313
TI  - Monoepoxy octadecadienoates and monoepoxy octadecatrienoates 2: mass spectral
      characterization.
AB  - Methyl esters of C18 polyunsaturated fatty acids, including gamma-linolenic acid,
      alpha-linolenic acid and stearidonic acid, were epoxidised using m
      chloroperbenzoic acid. Nine monoepoxides were obtained by normal-phase HPLC,
      identified using LC-MS and NMR, and characterized by NMR spectroscopy and mass
      spectrometry. This study is focused on structural characterization using LC-MS
      and LC/APCI/MS/MS. The elution profiles of these monoepoxides in RP-HPLC are
      determined as 12,13->9,10->6,7-epoxy, 9,10->15,16->12,13-epoxy and 15,16->12,13
      >9,10-epoxy derivatives of gamma-linolenic, alpha-linolenic and stearidonic acid
      methyl esters, respectively. The major diagnostic fragmentations in MS/MS
      identified are postulated to be induced by cleavages of the epoxide ring and
      alpha-bond cleavage to the epoxy group from [M+H]+ and/or [M+H-MeOH]+.

PMID- 18339314
TI  - Monoepoxy octadecadienoates and monoepoxy octadecatrienoates 1: NMR spectral
      characterization.
AB  - Methyl esters of gamma-linolenic acid, alpha-linolenic acid and stearidonic acid
      were epoxidised using m-chloroperbenzoic acid to achieve nine cis-monoepoxy-C18
      fatty acid methyl esters (FAMEs), including novel methyl cis-monoepoxy
      derivatives of stearidonic acid and a cis-6,7-epoxy derivative of gamma-linolenic
      acid. These nine monoepoxy FAMEs were purified by normal-phase HPLC, identified
      by LC-MS, 1H and 13C NMR, and characterized by mass spectrometry and NMR
      spectroscopy. This study is focused on structural characterization of these C18
      monoepoxy FAMEs using techniques in NMR spectroscopy including 1H, 13C, 1H-1H
      correlated spectroscopy (COSY) and 1H-13C heteronuclear correlation (HETCOR). The
      proton and carbon NMR chemical shifts of the epoxide, the double bonds, and the
      interrupted methylenes are assigned. Also discussed is an interpretation of the
      1H and 13C NMR spectra of these monoepoxides including the changes in the 13C
      resonance of the olefinic carbons on the neighboring double bonds resulting from
      epoxide formation.

PMID- 18339315
TI  - Conformational and hydrational properties during the L(beta)- to L(alpha)- and
      L(alpha)- to H(II)-phase transition in phosphatidylethanolamine.
AB  - Differential scanning calorimetry (DSC) measurements have been carried out
      simultaneously with small- and wide-angle X-ray scattering recordings on
      liposomal dispersions of stearoyl-oleoyl-phosphatidylethanolamine (PE) in a
      temperature range from 20 to 80 degrees C. The main transition temperature, T(m),
      was determined at 30.9 degrees C with an enthalpy of 28.5 kJ/mol and the lamellar
      to-inverse hexagonal phase transition temperature, T(hex), at 61.6 degrees C with
      an enthalpy of 3.8 kJ/mol. Additionally highly resolved small angle X-ray
      diffraction experiments performed at equilibrium conditions allowed a reliable
      decomposition of the lattice spacings into hydrophobic and hydrophilic structure
      elements as well as the determination of the lipid interface area of the lamellar
      gel-phase (L(beta)), the fluid lamellar phase (L(alpha)) and of the inverse
      hexagonal phase (H(II)). The rearrangement of the lipid matrix and the coincident
      change of free water per lipid is illustrated for both transitions. Last,
      possible transition mechanisms are discussed on a molecular level.

PMID- 18339316
TI  - Organic acid disorders detected by urine organic acid analysis: twelve cases in
      Thailand over three-year experience.
AB  - BACKGROUND: Disorders of organic acid (OA) metabolism are generally detected by
      qualitative analysis of urine organic acids by gas chromatography/mass
      spectrometry (GC/MS) which was well established in developed countries since
      1980s. Confirmation of the diagnosis of organic acid disorders by OA analysis,
      enzyme analysis and molecular study is a difficult task in developing countries.
      METHODS: During 2001-2004, we had analysed 442 urine samples in 365 patients and
      identified 12 cases of organic acid disorders. RESULTS: We identified the
      following disorders: alkaptonuria (ALK)=1, isovaleric acidemia (IVA)=3, propionic
      acidemia (PA)=2, methylmalonic acidemia (MMA)=3, glutaric aciduria, type I (GA
      I)=1, multiple carboxylase deficiency (MCD)=1, and glutaric acidemia, type II (GA
      II)=1. CONCLUSIONS: OA disorders had never been diagnosed in Thailand before,
      until GC/MS technology was introduced to Thailand in 2001. Urine OA analysis also
      provided a diagnostic clue to other inborn errors of metabolism including amino
      acid disorders, urea cycle disorders, disorders of carbohydrate metabolism, and
      mitochondrial fatty acid oxidation disorders. Since then, we were able to
      diagnose numerous disorders, which led to prompt treatment and better outcome in
      our patients.

PMID- 18339317
TI  - Relationship between CD40 ligand expression and B type natriuretic peptide levels
      in patients with chronic heart failure.
AB  - BACKGROUND: Inflammation plays a pathogenic role in the development of chronic
      heart failure (CHF). Increasing evidence shows that CD40-CD40 ligand (CD40L)
      interaction plays a pathogenic role in inflammatory disorders. We assessed
      whether CD40 ligand expression was abnormal in patients with CHF. METHODS: Twenty
      normal controls and 86 patients with CHF were investigated. The expression of
      CD40L on platelets was analyzed by indirect-immunofluorescence flow cytometry,
      and the soluble CD40L (sCD40L) level was determined by a commercially available
      enzyme-linked immunosorbent assay (ELISA). B type natriuretic peptide (BNP) was
      measured by radioimmunoassay. RESULTS: All patients with CHF showed a significant
      increased expression of CD40L (32.3+/-13.9 MFI) on platelets and sCD40L levels
      (20.5+/-8.6 microg/l) compared with controls(p<0.0001). CD40L expression on
      platelets and sCD40L levels positively correlated with New York Heart Association
      (NYHA) functional class, left ventricular ejection fraction and BNP levels in
      CHF. CONCLUSIONS: Patients with CHF showed increased expression of CD40L system,
      which may create a pathogenic role in the development and progression of CHF.

PMID- 18339318
TI  - Rapid genotyping of known mutations and polymorphisms in beta-globin gene based
      on the DHPLC profile patterns of homoduplexes and heteroduplexes.
AB  - BACKGROUND: Beta-thalassemia represents a great heterogeneity as over 200
      mutations have been identified for the beta-globin gene responsible for this
      disease. A rapid genotyping test with high accuracy, selectivity, and
      reproducibility suitable for the determination of known mutations is needed for
      prenatal screening and post-natal diagnosis of this disease in clinical setting.
      DESIGN AND METHODS: We have performed the validation of a DHPLC assay for direct
      genotyping of known causative mutations in beta-globin gene using the
      chromatographic pattern-based strategy under partially-denaturing conditions.
      RESULTS: DHPLC assay was established based on the analysis of 795 DNA samples
      from a group of various genotypes for the 20 mutations and 8 polymorphisms in
      beta-globin gene then validated on 319 tests in a blind study. The results
      obtained with this assay were in concordance with the results obtained by DNA
      sequence analysis. CONCLUSION: This simple method can meet the requirements of
      direct genotyping of known beta-thalassemia mutations and/or polymorphisms in the
      clinical setting for Chinese and in general as a model for other populations.

PMID- 18339319
TI  - Molecular evaluation of apoptotic versus antiapoptotic angiogenic markers in
      hepatocellular carcinoma.
AB  - OBJECTIVE: To assess the role of HO-1 in HCC progression and to study the
      expression of apoptotic factors represented by TNF-alpha, and Fas-L versus
      antiapoptotic and angiogenic factors represented by HO-1, TGF-beta, HGF, and VEGF
      in HCC compared to non cancerous cirrhotic liver. DESIGN AND METHODS: Liver
      biopsies were taken from twelve patients with grade II HCC confined to the liver
      and twelve patients with non cancerous liver cirrhosis (served as control). RT
      PCR of previous genes was evaluated. RESULTS: HO-1, VEGF, HGF, and TNF-alpha
      genes were significantly increased (P<0.05) in HCC compared to control. Fas-L
      showed a significant decrease (P<0.05) in HCC compared to control. TGF-beta was
      higher in HCC than control but the difference was not statistically significant
      (P>0.05). HGF showed significant positive correlation with HO-1 (r=0.8217,
      P=0.001). CONCLUSION: HCC is associated with increased expression of VEGF, HGF,
      and TGF-beta, and with suppression of Fas-L. In addition, HO-1 is highly
      significantly expressed in HCC. The significant positive correlation between HO-1
      and HGF was first reported in Egyptian human liver biopsies, and this suggests
      that it may play a role in the progression of hepatocellular carcinoma.

PMID- 18339320
TI  - Cyclooxygenase-2 induction by adiponectin is regulated by a sphingosine kinase-1
      dependent mechanism in cardiac myocytes.
AB  - The adipose-derived plasma protein, adiponectin (APN), has various protective
      effects on cardiovascular diseases. In this study, we show that endogenous APN is
      required for full cyclooxygenase-2 (COX-2) induction by ischemia-reperfusion
      injury in the heart in vivo. In rat neonatal cardiac myocytes, APN-induced COX-2
      expression was reduced by treatment with a sphingosine kinase-1 (SphK-1)
      inhibitor or siRNA targeting SphK-1. Treatment with a sphingosine-1-phosphate
      (S1P) receptor antagonist also diminished COX-2 expression in response to APN
      stimulation. These findings suggest that APN is a physiological regulator of COX
      2 signaling in the heart and that this regulation occurs in part via a SphK-1-S1P
      receptor dependent mechanism in cardiac myocytes.

PMID- 18339321
TI  - MeCP2 preferentially binds to methylated linker DNA in the absence of the
      terminal tail of histone H3 and independently of histone acetylation.
AB  - Methyl CpG binding protein 2 (MeCP2) is a basic protein that contains a DNA
      methyl binding domain. The mechanism by which the highly positive charge of MeCP2
      and its ability to bind methylated DNA contribute to the specificity of its
      binding to chromatin has long remained elusive. In this paper, we show that MeCP2
      binds to nucleosomes in a very similar way to linker histones both in vitro and
      in vivo. However, its binding specificity strongly depends on DNA methylation. We
      also observed that as with linker histones, this binding is independent of the
      core histone H3 N-terminal tail and is not affected by histone acetylation.

PMID- 18339322
TI  - An urokinase receptor antagonist that inhibits cell migration by blocking the
      formyl peptide receptor.
AB  - Urokinase receptor (uPAR) plays a key role in physiological and pathological
      processes sustained by an altered cell migration. We have developed peptides
      carrying amino acid substitutions along the Ser(88)-Arg-Ser-Arg-Tyr(92) (SRSRY)
      uPAR chemotactic sequence. The peptide pyro glutamic acid (pGlu)-Arg-Glu-Arg-Tyr
      NH2 (pERERY-NH(2)) shares the same binding site with SRSRY and competes with N
      formyl-Met-Leu-Phe (fMLF) for binding to the G-protein-coupled N-formyl-peptide
      receptor (FPR). pERERY-NH(2) is a dose-dependent inhibitor of both SRSRY- and
      fMLF-directed cell migration, and prevents agonist-induced FPR internalization
      and fMLF-dependent ERK1/2 phosphorylation. pERERY-NH(2) is a new and potent uPAR
      inhibitor which may suggest the generation of new pharmacological treatments for
      pathological conditions involving increased cell migration.

PMID- 18339323
TI  - Sumoylation is critical for DJ-1 to repress p53 transcriptional activity.
AB  - Sumoylation is an important post-translational modification, which is also
      involved in the pathogenesis of many neurodegenerative diseases. We previously
      reported that DJ-1 decreases Bcl-2 associated X protein expression through
      repressing p53 transcriptional activity. Here we show that DJ-1(K130R), the non
      sumoylatable mutant form of DJ-1, shifts from nucleus to cytoplasm, fails to
      repress p53 transcriptional activity and loses its protective function against
      ultraviolet induced cell death. Our findings suggest that sumoylation is critical
      for DJ-1 to repress p53 transcriptional activity.

PMID- 18339324
TI  - SLP-2 interacts with prohibitins in the mitochondrial inner membrane and
      contributes to their stability.
AB  - Stomatin is a member of a large family of proteins including prohibitins, HflK/C,
      flotillins, mechanoreceptors and plant defense proteins, that are thought to play
      a role in protein turnover. Using different proteomic approaches, we and others
      have identified SLP-2, a member of the stomatin gene family, as a component of
      the mitochondria. In this study, we show that SLP-2 is strongly associated with
      the mitochondrial inner membrane and that it interacts with prohibitins.
      Depleting HeLa cells of SLP-2 lead to increased proteolysis of prohibitins and of
      subunits of the respiratory chain complexes I and IV. Further supporting the role
      of SLP-2 in regulating the stability of specific mitochondrial proteins, we found
      that SLP-2 is up-regulated under conditions of mitochondrial stress leading to
      increased protein turnover. These data indicate that SLP-2 plays a role in
      regulating the stability of mitochondrial proteins including prohibitins and
      subunits of respiratory chain complexes.

PMID- 18339325
TI  - The nuclear localization of Drosophila Hsp27 is dependent on a monopartite
      arginine-rich NLS and is uncoupled from its association to nuclear speckles.
AB  - Drosophila Hsp27 is a small heat shock protein displaying exclusive nuclear
      localization both before and after heat shock. However, the mechanism implicated
      in this nuclear localization as well as the required sequences, are undefined.
      This study identifies the Hsp27 sequences mediating its nuclear localization. The
      generation of chimeric fusions between Hsp27 and Hsp23, a small heat shock
      protein displaying exclusive cytoplasmic localization, delineated a stretch of 15
      amino acids containing a nuclear-targeting activity. Site-directed mutagenesis
      within this region unveiled the implication of three arginine residues (R54-R55
      R56), which differentially combine to form a novel kind of nuclear localization
      signal (NLS). Abrogation of the nuclear localization signal activity indicated
      that Drosophila Hsp27 could still enter the nucleus to associate with nuclear
      speckles in a NLS-independent fashion. Mutagenesis of a putative nuclear export
      signal unveiled two leucine residues (L50 and L52) specifically involved in the
      association of Hsp27 to nuclear speckles and revealed novel nuclear structures
      formed by this Hsp27 mutant. The present study identifies two distinct sets of
      sequences respectively mediating the nuclear import of Hsp27 and its association
      to nuclear speckles. These two phenomena are uncoupled and can be separately
      abrogated.

PMID- 18339326
TI  - Fructose-induced structural and functional modifications of hemoglobin:
      implication for oxidative stress in diabetes mellitus.
AB  - Increased fructose concentration in diabetes mellitus causes fructation of
      several proteins. Here we have studied fructose-induced modifications of
      hemoglobin. We have demonstrated structural changes in fructose-modified
      hemoglobin (Fr-Hb) by enhanced fluorescence emission with excitation at 285 nm,
      more surface accessible tryptophan residues by using acrylamide, changes in
      secondary and tertiary structures by CD spectroscopy, and increased
      thermolability by using differential scanning calorimetry in comparison with
      those of normal hemoglobin, HbA(0). Release of iron from hemoglobin is directly
      related with the extent of fructation. H2O2-induced iron release from Fr-Hb is
      significantly higher than that from HbA(0). In the presence of H2O2, Fr-Hb
      degrades arachidonic acid, deoxyribose and plasmid DNA more efficiently than
      HbA(0), and these processes are significantly inhibited by desferrioxamine or
      mannitol. Thus increased iron release from Fr-Hb may cause enhanced formation of
      free radicals and oxidative stress in diabetes. Compared to HbA(0), Fr-Hb
      exhibits increased carbonyl formation, an index of oxidative modification.
      Functional modification in Fr-Hb has also been demonstrated by its decreased
      peroxidase activity and increased esterase activity in comparison with respective
      HbA(0) activities. Molecular modeling study reveals Lys 7alpha, Lys 127alpha and
      Lys 66beta to be the probable potential targets for fructation in HbA(0).

PMID- 18339327
TI  - Membrane type sialidase inhibits the megakaryocytic differentiation of human
      leukemia K562 cells.
AB  - The membrane type sialidase (Neu3) has been suggested to participate in cell
      growth, migration and differentiation. To determine whether a Neu3 is able to
      modulate megakaryocytic differentiation of K562 cells, we studied the functional
      significance of human Neu3 induced by phorbol 12-myristate 13-acetate (PMA).
      Northern blot and reverse transcription-polymerase chain reaction (RT-PCR)
      indicated that the induction of hST3Gal V, which synthesizes ganglioside GM3 and
      reduction of Neu3 by PMA, are linked for the expression of differentiation marker
      protein, CD41b surface antigen. To elucidate the mechanism underlying the down
      regulation of the CD41b surface antigen expression when Neu3 gene is expressed in
      PMA-treated cells, we characterized the Neu3-mediated signaling pathway. Neu3
      overexpression inhibited the PMA-induced ERK1/2 and p38 MAPK phosphorylation in
      the K562 cells. Down-regulation of expression of CD41b surface antigen was
      dependent on expression of Neu3 gene. However, a Neu3 inhibitor Neu5Ac2en induced
      morphological changes, showing megakaryocytic differentiation of K562 cells, with
      expression of CD41b surface antigen, while a specific glucosylceramide synthase
      inhibitor PDMP inhibited megakaryocytic differentiation of K562 cells. The
      molecular mechanisms involved in Neu3-involved inhibition of CD41b surface
      antigen expression in K562 cells have been suggested: the Neu3 degrades membrane
      sialic acids and the resulting signaling pathway of the PKC/ERKs/p38 MAPK is down
      regulated, causing a decrease in CD41b surface antigen expression and inhibition
      of megakaryocytic differentiation of K562 cells.

PMID- 18339328
TI  - Alzheimer's disease protein Abeta1-42 does not disrupt isolated synaptic
      vesicles.
AB  - Synaptic vesicles are central to neurotransmission and cognition. Studies of the
      Alzheimer's disease (AD) associated peptide, amyloid beta (Abeta), suggest that
      it has the potential to non-specifically solubilize or permeabilize membranes and
      that it has detergent and pore-forming properties. Damage to the membrane or
      integrity of synaptic vesicles could compromise its function. We test the
      hypothesis that the intact synaptic vesicle is a direct site of attack by Abeta1
      42 in AD pathology by examining the properties of individual isolated vesicles
      exposed to Abeta1-42. In particular, we compared the rate of leakage of dye
      molecules from synaptic vesicles, the rate of proton permeation across the
      membrane of the vesicle, and the rate of active proton transport into the vesicle
      interior in the presence and absence of Abeta1-42. From these experiments, we
      conclude that isolated synaptic vesicles are not disrupted by Abeta1-42.

PMID- 18339329
TI  - Subcellular localization of prion proteins and the 37 kDa/67 kDa laminin receptor
      fused to fluorescent proteins.
AB  - The 37 kDa/67 kDa laminin receptor LRP/LR acts as a receptor for both PrPc and
      PrPSc at the cell surface. Here, we further analyzed the subcellular localization
      of fluorescent labeled prion protein (PrP) and laminin receptor (LRP/LR)
      molecules. We show that EGFP-PrP is localized at the cell surface and in a
      perinuclear compartment, respectively. In contrast, a DsRed-DeltaSP-PrP mutant
      lacking the signal peptide is almost exclusively found in the nucleus but does
      not colocalize with heterochromatin. Interestingly, LRP-DsRed efficiently
      colocalizes with EGFP-PrP in the perinuclear compartment and LRP-ECFP partly
      colocalizes with DsRed-DeltaSP-PrP in the nucleus, respectively. We conclude that
      the interactions of PrP and LRP/LR are not restricted to the cell surface but
      occur also in intracellular compartments suggesting a putative role of LRP/LR in
      the trafficking of PrP molecules.

PMID- 18339330
TI  - MH1 domain of SMAD4 binds N-terminal residues of the homeodomain of Hoxc9.
AB  - Smad family proteins mediate signaling initiated by bone morphogenetic proteins
      (BMPs). Upon BMP stimulation, the Smads such as Smad4 can interact directly with
      Hox proteins and suppress their DNA-binding activity. Although the interaction
      between the MAD-homology 1 (MH1) domain of Smad4 and Hox was found to regulate
      the transcription activity of Hox proteins, the molecular mechanism is not well
      characterized and direct contact residues remain to be elucidated. In the present
      study, the interaction between the recombinant homeodomain (HD) of Hoxc9 and MH1
      domain of Smad4 was investigated with the use of the GST pull-down assay, surface
      plasmon resonance (SPR) analysis as well as multidimensional nuclear magnetic
      resonance (NMR) techniques. The Hoxc9-HD was precipitated with the GST-fused
      Smad4-MH1 but not with GST alone, demonstrating a direct interaction between
      Hoxc9-HD and Smad4-MH1 in vitro. SPR measurement further confirmed a moderately
      strong interaction (K(d) approximately 400 nM) between these two domains.
      Moreover, NMR titration experiments showed that a strong and specific binding
      occurred between Smad4-MH1 and Hoxc9-HD. NMR triple-resonance experiments and
      backbone assignments revealed that the N-terminal arm of Hoxc9-HD, spanning the
      positive-charged DNA-binding segment of Arg190-Arg196, was intimately involved in
      the interaction with Smad4-MH1. Ala-substitutions of Arg190-Arg196 led to the
      loss of interaction between Hoxc9-HD and Smad4-MH1 in both GST-pull down assay
      and SPR analysis; further provided functional evidence for the critical role of
      this positive-charged region in binding to Smad4-MH1. This suggested that Smad4
      MH1 could occupy one of the DNA binding sites of Hoxc9 and consequently inhibits
      its transcription activity. The above results are in good agreement and yield the
      first insight into the interaction between the homeodomain of Hox proteins and
      the conserved MH1 domain of Smad family proteins.

PMID- 18339331
TI  - Flexibility and enzyme activity of NADH oxidase from Thermus thermophilus in the
      presence of monovalent cations of Hofmeister series.
AB  - Recently, we have shown that anions of Hofmeister series affect the enzyme
      activity through modulation of flexibility of its active site. The enzyme
      activity vs. anion position in Hofmeister series showed an unusual bell-shaped
      dependence. In the present work, six monovalent cations (Na(+), Gdm(+), NH(4)(+),
      Li(+), K(+) and Cs(+)) of Hofmeister series with chloride as a counterion have
      been studied in relation to activity and stability of flavoprotein NADH oxidase
      from Thermus thermophilus (NOX). With the exception of strongly chaotropic
      guanidinium cation, cations are significantly less effective in promoting the
      Hofmeister effect than anions mainly due to repulsive interactions of positive
      charges around the active site. Thermal denaturations of NOX reveal unfavorable
      electrostatic interaction at the protein surface that may be shielded to
      different extent by salts. Michaelis-Menten constants for NADH, accessibility of
      the active site as reflected by Stern-Volmer constants and activity of NOX at
      high cation concentrations (1-2 M) show bell-shaped dependences on cation
      position in Hofmeister series. Our analysis indicates that in the presence of
      kosmotropic cations the enzyme is more stable and possibly more rigid than in the
      presence of chaotropic cations. Molecular dynamic (MD) simulations of NOX showed
      that active site switches between open and closed conformations [J. Hritz, G.
      Zoldak, E. Sedlak, Cofactor assisted gating mechanism in the active site of NADH
      oxidase from Thermus thermophilus, Proteins 64 (2006) 465-476]. Enzyme activity,
      as well as substrate binding, can be regulated by the salt mediated perturbation
      of the balance between open and closed forms. We propose that compensating effect
      of accessibility and flexibility of the enzyme active site leads to bell-shaped
      dependence of the investigated parameters.

PMID- 18339332
TI  - Orbital emphysema after nose blowing.

PMID- 18339333
TI  - Pediatric nursing: scope and standards of practice: a unified professional
      effort.

PMID- 18339334
TI  - The impact of unintentional pediatric trauma: a review of pain, acute stress, and
      posttraumatic stress.
AB  - This article reviews current research on acute stress disorder (ASD) and
      posttraumatic stress disorder (PTSD) resulting from pediatric simple (i.e.,
      single, unpredictable, and unintentional) physical injury and how pain may act as
      both a trigger and a coexisting symptom. Although several studies have explored
      predictors of ASD and PTSD, as well as the relationship between these conditions
      in adults, there is less research on ASD and PTSD in children and adolescents.
      This review highlights the importance of early detection of pain and acute stress
      symptoms resulting from pediatric unintentional physical injury in the hopes of
      preventing long-term negative outcomes, such as the potential development of PTSD
      and associated academic, social, and psychological problems.

PMID- 18339335
TI  - Case study of a transtheoretical case management approach to addressing childhood
      obesity.
AB  - Childhood obesity is an increasing health concern that is strongly associated
      with chronic health problems persisting into adulthood. Obesity in childhood is
      resistant to interventions that involve only recommendations to decrease caloric
      intake and to increase caloric expenditure. The challenge with this approach to
      childhood obesity is twofold: It is neither theoretically based nor does it
      consider the children's or their parent's perceptions of their health problems.
      Of significance, this traditional approach also ignores the transition along the
      stages of behavioral change. Case management has proven to be successful in
      managing various chronic health problems in both adults and children. This case
      study will present a new intervention model to treat childhood obesity based on
      the transtheoretical framework utilizing case management in a primary care
      setting.

PMID- 18339336
TI  - Fathers of children and adolescents with diabetes: what do we know?
AB  - Knowing how fathers contribute to child outcomes is critical in the clinical
      management of children who have type 1 diabetes. The purposes of this review were
      to synthesize what is known about the role of fathers and to determine directions
      for future research. Research studies that reported findings that encompassed
      fathers' perceptions, knowledge, coping and adjustment, and behavior in relation
      to their children with type 1 diabetes were reviewed. Research suggests that,
      although fathers are usually not the primary caregiver or manager of the routine
      day-to-day care, their contribution to the family through perceptions, knowledge,
      adjustment, and behavior may be associated with important disease management
      outcomes.

PMID- 18339337
TI  - Can the death of a child be good?
AB  - Fifty-four thousand children die each year despite the advances in care for
      children with acute and chronic illnesses. Demands for improved palliative and
      end-of-life care for children exist. Good death is a concept frequently used in
      the adult hospice movement. However, how can the death of a child be good?
      Analysis of good death can assist pediatric nurses to understand the concept and
      provide a framework for nurses in the clinical and research arenas to work
      together to develop and provide evidence-based, developmentally appropriate care
      for dying children and their families.

PMID- 18339338
TI  - The effectiveness of a multimedia intervention on parents' knowledge and use of
      vehicle safety systems for children.
AB  - Trauma due to road crashes is the leading cause of death and injury in Canadian
      children younger than 14 years, despite mandatory use of vehicle restraints since
      1977. A multisite intervention study using a pretest-posttest design was
      conducted in four Ontario cities to test the effectiveness of an educational
      program on parents' knowledge of safety system use for children (0-12 years) 6
      weeks following the educational intervention. The sample consisted of 418
      families who reported on 732 children. Results indicated that knowledge increased
      significantly following the intervention. Use of professional sources of
      information was an important factor that is linked with increased parents'
      knowledge.

PMID- 18339339
TI  - Child health pays.

PMID- 18339340
TI  - Interpretation of the large red-and-white visual analog scale by children
      compared with adults.
AB  - The red-and-white visual analog scale (VAS) is a modification of the traditional
      VAS. The purpose of this study was to compare how children of various ages and
      adults rate their anticipatory pain intensity on the red-and-white VAS. One
      hundred children were interviewed as part of the anesthesiologist's preoperative
      visit before elective eye surgery. For comparison, 50 healthy adults were
      interviewed in a similar manner. The medians and ranges describing mild,
      moderate, and severe pain, or pain intensity at which medicine would be
      requested, did not differ between preschool children, young schoolchildren, and
      adolescents or between children and adults. The median score of anticipated need
      for pain medication was 50% of the maximum for children.

PMID- 18339341
TI  - Pediatric issues in disaster preparedness: meeting the educational needs of
      nurses-are we there yet?
AB  - Children have unique physical, emotional, and developmental needs making them
      particularly vulnerable during disasters. Most existing disaster preparedness
      courses lack a pediatric perspective. This article describes a pediatric disaster
      preparedness program presented to pediatric nurses in an urban, Level 1 trauma
      center. Survey results from the participants prior to the program revealed a lack
      of awareness of pediatric issues. Although the program resulted in an immediate
      improvement in awareness, retention fell back to precourse levels 2 years later.
      We conclude that pediatric disaster preparedness training should be integrated
      into hospital nursing curriculum on a regular basis.

PMID- 18339342
TI  - Guidance for off-label use of drugs.

PMID- 18339343
TI  - Idraparinux for stroke prevention in atrial fibrillation.

PMID- 18339344
TI  - Polio eradication nears the end game.

PMID- 18339348
TI  - Paraneoplastic syndromes of the CNS.
AB  - Major advances in the management of paraneoplastic neurologic disorders (PND)
      include the detection of new antineuronal antibodies, the improved
      characterisation of known syndromes, the discovery of new syndromes, and the use
      of CT and PET to reveal the associated tumours at an early stage. In addition,
      the definition of useful clinical criteria has facilitated the early recognition
      and treatment of these disorders. In this article, we review some classic
      concepts about PND and recent clinical and immunological developments, focusing
      on paraneoplastic cerebellar degeneration, opsoclonus-myoclonus, and
      encephalitides affecting the limbic system.

PMID- 18339349
TI  - Acute ischaemic stroke and infection: recent and emerging concepts.
AB  - The relation between acute ischaemic stroke and infection is complex. Infection
      appears to be an important trigger that precedes up to a third of ischaemic
      strokes and can bring about stroke through a range of potential mechanisms.
      Infections that present subsequent to stroke also complicate up to a third of
      cases of stroke and might worsen outcome. Inflammatory responses, which are a
      defence mechanism against infection but can also be a pathogenic mechanism that
      precipitates stroke and neurological sequelae, are important features. Although
      factors such as stroke severity and dysphagia are important predictors of
      poststroke infection, there is evidence from experimental and clinical settings
      of impaired immunity or brain-induced immunodepression after stroke. Greater
      understanding of the relation between inflammation and both infection and
      ischaemic mechanisms is needed. This might be particularly important because new
      treatment strategies for acute ischaemic stroke are being investigated, including
      those that modulate cytokines and the immune system.

PMID- 18339350
TI  - Epidemiology and comorbidity of headache.
AB  - The burden associated with headache is a major public health problem, the true
      magnitude of which has not been fully acknowledged until now. Globally, the
      percentage of the adult population with an active headache disorder is 47% for
      headache in general, 10% for migraine, 38% for tension-type headache, and 3% for
      chronic headache that lasts for more than 15 days per month. The large costs of
      headache to society, which are mostly indirect through loss of work time, have
      been reported. On the individual level, headaches cause disability, suffering,
      and loss of quality of life that is on a par with other chronic disorders. Most
      of the burden of headache is carried by a minority who have substantial and
      complicating comorbidities. Renewed recognition of the burden of headache and
      increased scientific interest have led to a better understanding of the risk
      factors and greater insight into the pathogenic mechanisms, which might lead to
      improved prevention strategies and the early identification of patients who are
      at risk.

PMID- 18339351
TI  - Person-centred care of people with severe Alzheimer's disease: current status and
      ways forward.
AB  - When caring for people with severe Alzheimer's disease (AD), the concept of the
      person being central is increasingly advocated in clinical practice and academia
      as an approach to deliver high-quality care. The aim of person-centred care,
      which emanates from phenomological perspectives on AD, is to acknowledge the
      personhood of people with AD in all aspects of their care. It generally includes
      the recognition that the personality of the person with AD is increasingly
      concealed rather than lost; personalisation of the person's care and their
      environment; offering shared decision-making; interpretation of behaviour from
      the viewpoint of the person; and prioritising the relationship as much as the
      care tasks. However, questions remain about how to provide, measure, and explore
      clinical outcomes of person-centred care. In this Review, we summarise the
      current knowledge about person-centred care for people with severe AD and
      highlight the areas in need of further research.

PMID- 18339352
TI  - Treatment-resistant chronic headaches and focal pachymeningitis in a 46-year-old
      man: a rare presentation of Wegener's granulomatosis.

PMID- 18339353
TI  - Task specificity of finger dexterity tests.
AB  - Finger dexterity tests are generally used to assess performance decrease due to
      gloves, cold and pathology. It is generally assumed that the O'Connor and Purdue
      Pegboard test yield similar results. In this experiment we compared these two
      tests for dry conditions without gloves, and for dry and wet conditions with two
      types of Nytril gloves. In line with previous observations, wearing gloves caused
      a decrease in performance of about 12% for the O'Connor test and 9% for the
      Purdue test. Wetting the gloves prior to the test had no effect on the Purdue
      score. However, wetting the gloves increased the O'Connor performance
      significantly by 11%. The results show that the O'Connor and Purdue tests do not
      yield similar results and should be used selectively for specific tasks.

PMID- 18339354
TI  - Assessment of controls layout of Indian tractors.
AB  - Tractors in low-income countries are used both for farm and non-farm activities.
      Most of the tractors being manufactured in India are products of collaboration
      with other countries. The design of tractors manufactured in India has not
      changed much in the past five decades especially from an ergonomics point of
      view, because of economic considerations. This paper describes a tractor control
      layout assessment with respect to the Indian population and compares the location
      of controls with workspace envelopes and the IS12343 standard for commonly used
      tractors on Indian farms. Controls like steering, foot clutch, foot brake, foot
      accelerator are located in areas defined by IS12343 standard in some tractors but
      these are not placed in the workspace envelopes of the Indian population. This
      results in a mismatch between the workspace envelope and location of controls as
      defined by the standard. The controls need a complete change in their layout to
      be in the workspace envelopes, as this cannot be achieved by providing seat
      movement in the horizontal and vertical directions in the present tractor design.

PMID- 18339355
TI  - Investigation of flexible hose insertion forces and selected factors.
AB  - Flexible hoses are widely used in automobiles. Understanding the force required
      to insert a hose, independent of worker variation, is important for engineers,
      designers and health professionals. Various parameters affect the insertion
      forces including the interference between the hose and flange. Also, it has been
      observed that workers often add motions during the insertion process, including
      rotation and oscillation. This paper describes the effects of these parameters on
      axial insertion forces. A programmable mill was used to isolate the effects of
      four variables on hose insertion force: fit, insertion speed, rotational velocity
      and oscillation magnitude. The results show that the magnitude of the
      interference of the 19 mm inside diameters (ID) heater hose and the flange, and
      the insertion technique affect the insertion forces; resulting in a range of
      insertion forces from 11.1+/-0.2 to 128.4+/-11.3N.

PMID- 18339356
TI  - Expression of podoplanin in the mouse salivary glands.
AB  - OBJECTIVE: Podoplanin is one of the most highly expressed lymphatic-specific
      genes. Here, we report the distribution of cells expressing podoplanin in mouse
      salivary glands. DESIGN: We immunohistochemically investigated the distribution
      of cells expressing podoplanin in mouse major salivary glands by laser-scanning
      microscopy. The expression of endothelial cell marker PECAM-1 was tested to
      discriminate lymphatic endothelium from salivary gland cells, and myoepithelial
      cells were identified by an antibody for P-cadherin. RESULTS: The podoplanin
      expression was rarely found in acini of the parotid gland but clearly found at
      the basal portion of acini in the submandibular and sublingual glands. The number
      of portion reacted with anti-podoplanin is greater in the sublingual gland than
      in the submandibular gland. The expression was also found at the basal portion of
      ducts in all major salivary glands. The P-cadherin expression was rarely found in
      acini of the parotid gland but found in acini of the sublingual gland and on
      ducts in parotid and sublingual glands, corresponding to the area of podoplanin
      expression. CONCLUSIONS: It was suggested that the acinar and myoepithelial cells
      in the salivary glands have the ability to express podoplanin, and that the
      expression may be concerned with the mucous saliva excretion.

PMID- 18339357
TI  - Implicit and explicit self-schema in active deluded, remitted deluded, and
      depressed patients.
AB  - The main objective of this study was to analyze the hypothesis that patients with
      persecutory delusions would show a depressive-type self-concept when assessed
      with implicit measures of self-schema (i.e., a free recall test of self-relevant
      adjectives) but would show a normal self-concept when assessed with explicit
      measures (i.e., a self-concept questionnaire and a task requiring endorsement of
      self-relevant adjectives). The sample consisted of 136 participants (40 acute
      deluded participants, 25 remitted deluded participants, 35 depressed patients and
      36 normal controls). Our results revealed that both groups of deluded
      participants showed no significant discrepancy between explicit and implicit
      measures of self-concept. These findings do not support the hypothesis of an
      implicit negative cognitive schema in persecutory deluded participants.

PMID- 18339358
TI  - Action monitoring in boys with attention-deficit/hyperactivity disorder, their
      nonaffected siblings, and normal control subjects: evidence for an endophenotype.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a very common and
      highly heritable child psychiatric disorder associated with dysfunctions in
      fronto-striatal networks that control attention and response organization. The
      aim of this study was to investigate whether features of action monitoring
      related to dopaminergic functions represent endophenotypes that are brain
      functions on the pathway from genes and environmental risk factors to behavior.
      METHODS: Action monitoring and error processing as indicated by behavioral and
      electrophysiological parameters during a flanker task were examined in boys with
      ADHD combined type according to DSM-IV (n = 68), their nonaffected siblings (n =
      18), and healthy control subjects with no known family history of ADHD (n = 22).
      RESULTS: Boys with ADHD displayed slower and more variable reaction-times. Error
      negativity (Ne) was smaller in boys with ADHD compared with healthy control
      subjects, whereas nonaffected siblings displayed intermediate amplitudes
      following a linear model predicted by genetic concordance. The three groups did
      not differ on error positivity (Pe). The N2 amplitude enhancement due to conflict
      (incongruent flankers) was reduced in the ADHD group. Nonaffected siblings also
      displayed intermediate N2 enhancement. CONCLUSIONS: Converging evidence from
      behavioral and event-related potential findings suggests that action monitoring
      and initial error processing, both related to dopaminergically modulated
      functions of anterior cingulate cortex, might be an endophenotype related to
      ADHD.

PMID- 18339359
TI  - Meta-analysis of the cognitive effects of the catechol-O-methyltransferase gene
      Val158/108Met polymorphism.
AB  - BACKGROUND: Cognitive endophenotypes may further our understanding of the genetic
      basis of psychiatric disorders, and the catechol-O-methyltransferase (COMT) gene
      is a promising candidate gene for both cognitive function and disorder. We
      conducted a meta-analysis of reported associations between the COMT Val158/108Met
      polymorphism and measures of memory and executive function. METHODS: The PubMed
      database was searched for studies relating cognitive functions and the COMT
      Val158/108Met polymorphism. This enabled meta-analyses of six cognitive
      phenotypes (Trail Making task, verbal recall, verbal fluency, IQ score, n-back
      task, and Wisconsin Card Sorting Test). Data were extracted by two reviewers and
      included cognitive scores by COMT genotype, publication year, diagnostic status,
      ancestry, proportion of male participants, and whether genotype frequencies were
      consistent with Hardy-Weinberg equilibrium. RESULTS: We found no association
      between COMT genotype and the majority of phenotypes. There was evidence of
      association with IQ score (d = .06), which did not differ significantly by
      ancestry, sex, average sample age, or patient status. For the n-back task, there
      was no robust evidence for genetic association, but the effect size was
      significantly larger in patient (d = .40) than nonpatient (d = -.27) populations,
      larger in both samples with fewer male subjects, and those of greater average
      age. There was also evidence of publication bias and decreasing effect sizes with
      later publication. CONCLUSIONS: Despite initially promising results, the COMT
      Val158/108Met polymorphism appears to have little if any association with
      cognitive function. Publication bias may hamper attempts to understand the
      genetic basis of psychological functions and psychiatric disorders.

PMID- 18339360
TI  - In vivo characterization and dynamic receptor occupancy imaging of TPA023B, an
      alpha 2/alpha 3/alpha 5 subtype selective gamma-aminobutyric acid-a partial
      agonist.
AB  - BACKGROUND: A novel, high-affinity (.7-2.0 nmol) compound that selectively
      activates the alpha2, alpha 3, and alpha 5 (but not alpha1) gamma-aminobutyric
      acid-A (GABA(A)) receptor subtypes, TPA023B (2',6-difluoro-5'-[3-(1-hydroxy-1
      methylethyl) imidazo[1,2-b][1,2,4]triazin-7-yl][1,1'-biphenyl]-2-carbonitrile)
      was pharmacologically characterized and studied by means of positron emission
      tomography (PET) to determine dynamic occupancies of the benzodiazepine binding
      site of human brain GABA(A) receptors after a single oral dose. METHODS: Four
      healthy male volunteers were studied in a double-blind, randomized placebo
      controlled study of which three were given a single dose of 1.5 mg TPA023B and
      the fourth received placebo. The time course of GABA(A) receptor occupancy was
      determined with multiple dynamic [(11)C]flumazenil PET studies at pre-dose
      baseline and 5 and 24 hours after dose. Arterial sampling and full kinetic
      modeling with a two-compartment model was used to calculate parametric maps of
      receptor availability (distribution volume V(T)) and of occupancy. RESULTS: The
      GABA(A) receptor occupancy as determined from [(11)C]flumazenil V(T) values in
      all brain regions was reduced homogeneously, on average by 52.5 +/- 1.2% after 5
      hours and 46.4 +/- 6.0% after 24 hours. No serious adverse events were
      encountered in humans. CONCLUSIONS: Single oral doses of 1.5 mg of TPA023B
      correspond to average receptor occupancies in neocortical regions of 52% and 46%
      after 5 and 24 hours, respectively. Provided suitable ligands and quantification
      methods are available for the appropriate target, quantitative PET offers a
      unique tool for dynamic in vivo measurement of relevant on-site receptor
      occupancy.

PMID- 18339361
TI  - Childhood parental loss and adult hypothalamic-pituitary-adrenal function.
AB  - BACKGROUND: Several decades of research link childhood parental loss with risk
      for major depression and other forms of psychopathology. A large body of
      preclinical work on maternal separation and some recent studies of humans with
      childhood parental loss have demonstrated alterations of hypothalamic-pituitary
      adrenal (HPA) axis function that could predispose to the development of
      psychiatric disorders. METHODS: Eighty-eight healthy adults with no current Axis
      I psychiatric disorder participated in this study. Forty-four participants
      experienced parental loss during childhood, including 19 with a history of
      parental death and 25 with a history of prolonged parental separation. The loss
      group was compared with a matched group of individuals who reported no history of
      childhood parental separation or childhood maltreatment. Participants completed
      diagnostic interviews and questionnaires and the dexamethasone/corticotropin
      releasing hormone (Dex/CRH) test. Repeated measures general linear models were
      used to test the effects of parental loss, parental care, gender, and age on the
      hormone responses to the Dex/CRH test. RESULTS: Parental loss was associated with
      increased cortisol responses to the test, particularly in men. The effect of loss
      was moderated by levels of parental care; participants with parental desertion
      and very low levels of care had attenuated cortisol responses.
      Adrenocorticotropic hormone responses to the Dex/CRH test did not differ
      significantly as a function of parental loss. CONCLUSIONS: These findings are
      consistent with the hypothesis that early parental loss induces enduring changes
      in neuroendocrine function.

PMID- 18339362
TI  - Reinstating the ability of the motor cortex to modulate cutaneomuscular reflexes
      in hemicerebellectomized rats.
AB  - The pathways passing through the cerebellum calibrate cutaneomuscular responses.
      Indeed, the enhancement of cutaneomuscular responses associated with subthreshold
      high-frequency trains of stimulation applied on motor cortex following a period
      of peripheral repetitive stimulation (PRS) is prevented by hemicerebellectomy. We
      analysed the effects of low-frequency repetitive stimulation of motor cortex
      (LFRSM1) on interhemispheric inhibition (IHI) and on the modulation of
      cutaneomuscular reflexes in rats with left hemicerebellar ablation. IHI was
      assessed by paired-pulse method with a conditioning stimulus (CS) to M1 followed
      by a test stimulus (TS) to the opposite M1. LFRSM1 reduced IHI. Combination of
      LFRSM1 with PRS increased significantly the magnitudes of cutaneomuscular
      responses evoked ipsilaterally to the hemicerebellar ablation. The increase of
      the intensity of cutaneomuscular responses was correlated with the reduction of
      IHI. Excitability of anterior horn motoneurons pool, assessed by F-wave, remained
      unchanged. Conjunction of LFRSM1 with PRS can be used to restore the ability of
      the motor cortex to modulate the intensity of cutaneomuscular responses in case
      of extensive unilateral cerebellar lesion. This study underlines for the first
      time the potential role of callosal pathways in the deficits of corticomotor
      tuning of cutaneomuscular responses contralaterally to acute extensive cerebellar
      lesion.

PMID- 18339363
TI  - Copper deficiency results in AMP-activated protein kinase activation and
      acetylCoA carboxylase phosphorylation in rat cerebellum.
AB  - Copper (Cu) deficiency impairs cerebellar development including biosynthetic
      processes like myelination and synaptogenesis. The activity of cerebellar
      mitochondrial cuproenzyme cytochrome c oxidase is markedly lower in Cu deficient
      rat pups and is accompanied by higher lactate levels indicating mitochondrial
      inhibition. Cu deficiency impaired energy metabolism is thought to contribute to
      developmental delays, but specific mechanisms linking these phenomena have
      remained unexplored. AMP-activated protein kinase (AMPK) is a cellular energy
      sensor that is activated during mitochondrial inhibition and shuts down
      biosynthetic processes to help conserve cellular ATP levels. Activated AMPK
      phosphorylates and inhibits acetylCoA carboxylase (ACC), the first enzyme in
      fatty acid biosynthesis. We hypothesize that AMPK is activated and ACC inhibited
      in Cu deficient cerebella. Perinatal copper deficiency was studied in young rats
      in rapidly frozen cerebella. Compared to copper-adequate (Cu+) pups, copper
      deficient (Cu-) pups were hypothermic, had lower brain copper levels and markedly
      higher cerebellar lactate. Concentration of phosphorylated AMPK (pAMPK),
      indicating AMPK activation, was robustly higher in Cu- cerebella of rat pups at
      two ages and in two separate experiments. Compared to Cu+ cerebella, pACC content
      was significantly higher in all Cu- samples. Mechanisms leading to AMPK
      activation remain elusive. Higher AMP/ATP ratios and increased reactive nitrogen
      species (RNS) can lead to AMPK activation. ATP and AMP concentrations were
      unaltered and nitric oxide metabolites and 3-nitrotyrosine peptide levels
      remained unchanged in Cu- cerebella. AMPK activation may explain how ATP levels
      can be maintained even with a severe mitochondrial loss of CCO function.

PMID- 18339364
TI  - Organosulfur compounds alone or in combination with vitamin C protect towards N
      nitrosopiperidine- and N-nitrosodibutylamine-induced oxidative DNA damage in
      HepG2 cells.
AB  - The aim of this study was to investigate the protective effects of organosulfur
      compounds (OSCs) alone or in combination with vitamin C towards N
      nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA)-induced oxidative DNA
      damage in the single cell gel electrophoresis (SCGE)/HepG2 assay. Diallyl sulfide
      (DAS) did not protect against NDBA-induced oxidized purines, but it reduced the
      oxidized purines induced by NPIP (1 microM, 29%). The formation of
      formamidopyridine-DNA glycosylase (Fpg) sensitive sites induced by NPIP or NDBA
      was prevented by dipropyl sulfide (DPS) at concentrations of 1-10 microM (55-24%
      and 66-15%, respectively). The maximum reduction of the formation of Fpg
      sensitive sites induced by NPIP was observed at the highest concentration of
      diallyl disulfide (DADS) (2.5 microM, 38%). However, the oxidative DNA damage
      induced by NDBA was strongly reduced by DADS at the lowest concentration tested
      (0.1 microM, 92%). The oxidative DNA damage induced by NPIP or NDBA was prevented
      by all the concentrations of dipropyl disulfide (DPDS) (0.1-2.5 microM, 59-80%
      and 51-64%, respectively). DADS and DPDS, in combination with vitamin C showed an
      overall protective effect towards the formation of Fpg sensitive sites induced by
      NPIP and NDBA. However, the contribution of OSCs to the protective effect found
      in combined experiments might not be relevant, because it could be caused by
      vitamin C alone. One feasible mechanism by which OSCs exert their protective
      effects towards N-nitrosamine-induced oxidative DNA damage could be by modulation
      of phase I and II enzyme activities. DADS and DPDS (0.1-2.5 microM) exerted
      greater inhibition on CYP2E1 and CYP2A6 activity than DAS and DPS (1-50 microM).
      However, DAS and DADS (1 microM) exerted greater inhibition on CYP1A1 activity
      than DPS and DPDS (1 microM). DAS/DPS (50 microM) and DADS (2.5 microM) exerted a
      moderate increase of UDP-glucuronyltransferase (UGT1A4) activity, whereas DPDS
      (2.5 microM) had the most pronounced effect.

PMID- 18339365
TI  - Automatic classification of the acrosome status of boar spermatozoa using digital
      image processing and LVQ.
AB  - We consider images of boar spermatozoa obtained with an optical phase-contrast
      microscope. Our goal is to automatically classify single sperm cells as acrosome
      intact (class 1) or acrosome-damaged (class 2). Such classification is important
      for the estimation of the fertilization potential of a sperm sample for
      artificial insemination. We segment the sperm heads and compute a feature vector
      for each head. As a feature vector we use the gradient magnitude along the
      contour of the sperm head. We apply learning vector quantization (LVQ) to the
      feature vectors obtained for 320 heads that were labelled as intact or damaged
      using stains. A LVQ system with four prototypes (two for each class) allows us to
      classify cells with an overall test error of 6.8%. This is considered to be
      sufficient for semen quality control in an artificial insemination center.

PMID- 18339366
TI  - Cognitive techniques in medical information systems.
AB  - This paper presents the way of application of structural methods of Artificial
      Intelligence-in particular, linguistic mechanisms of semantic meaning reasoning
      for development of intelligent medical information systems. They also facilitate
      an in-depth analysis of the meaning presented in Diagnosis Support Information
      Systems used in analysis of selected medical examinations. This paper will
      present the mechanisms of pattern meaning description on selected examples of
      spinal cord image analysis. Presented approach for semantic reasoning will be
      based on the model of cognitive resonance, which will be applied to the task of
      interpreting the meaning of selected diagnostic images from the central nervous
      system. Such algorithms are aimed to construct an intelligent analysis module in
      medical IS. The application presented in this paper is of a research character
      and it serves the preparation of efficient lesion detection methods applied to a
      data set originating from magnetic and resonance examinations of the spine and
      spinal cord structures.

PMID- 18339367
TI  - Roles of FGFR3 during morphogenesis of Meckel's cartilage and mandibular bones.
AB  - To address the functions of FGFR2 and FGFR3 signaling during mandibular
      skeletogenesis, we over-expressed in the developing chick mandible, replication
      competent retroviruses carrying truncated FGFR2c or FGFR3c that function as
      dominant negative receptors (RCAS-dnFGFR2 and RCAS-dnFGFR3). Injection of RCAS
      dnFGFR3 between HH15 and 20 led to reduced proliferation, increased apoptosis,
      and decreased differentiation of chondroblasts in Meckel's cartilage. These
      changes resulted in the formation of a hypoplastic mandibular process and
      truncated Meckel's cartilage. This treatment also affected the proliferation and
      survival of osteoprogenitor cells in osteogenic condensations, leading to the
      absence of five mandibular bones on the injected side. Injection of RCAS-dnFGFR2
      between HH15 and 20 or RCAS-dnFGFR3 at HH26 did not affect the morphogenesis of
      Meckel's cartilage but resulted in truncations of the mandibular bones. RCAS
      dnFGFR3 affected the proliferation and survival of the cells within the
      periosteum and osteoblasts. Together these results demonstrate that FGFR3
      signaling is required for the elongation of Meckel's cartilage and FGFR2 and
      FGFR3 have roles during intramembranous ossification of mandibular bones.

PMID- 18339368
TI  - SrfB, a member of the Serum Response Factor family of transcription factors,
      regulates starvation response and early development in Dictyostelium.
AB  - The Serum Response Factor (SRF) is an important regulator of cell proliferation
      and differentiation. Dictyostelium discoideum srfB gene codes for an SRF
      homologue and is expressed in vegetative cells and during development under the
      control of three alternative promoters, which show different cell-type specific
      patterns of expression. The two more proximal promoters directed gene
      transcription in prestalk AB, stalk and lower-cup cells. The generation of a
      strain where the srfB gene has been interrupted (srfB(-)) has shown that this
      gene is required for regulation of actin-cytoskeleton-related functions, such as
      cytokinesis and macropinocytosis. The mutant failed to develop well in
      suspension, but could be rescued by cAMP pulsing, suggesting a defect in cAMP
      signaling. srfB(-) cells showed impaired chemotaxis to cAMP and defective lateral
      pseudopodium inhibition. Nevertheless, srfB(-) cells aggregated on agar plates
      and nitrocellulose filters 2 h earlier than wild type cells, and completed
      development, showing an increased tendency to form slug structures. Analysis of
      wild type and srfB(-) strains detected significant differences in the regulation
      of gene expression upon starvation. Genes coding for lysosomal and ribosomal
      proteins, developmentally-regulated genes, and some genes coding for proteins
      involved in cytoskeleton regulation were deregulated during the first stages of
      development.

PMID- 18339369
TI  - Estimated burden of blood lead levels 5 microg/dl in 1999-2002 and declines from
      1988 to 1994.
AB  - In light of recent data suggesting adverse health effects at blood lead levels
      (PbB) <10 microg/dl, lowering the current definition of elevated blood lead
      (>or=10 microg/dl) has been recommended. To ascertain the population level impact
      of such a change, we calculated the prevalence of PbB >or=5 microg/dl in 1-21
      year-old population in the United States. Furthermore, we characterized changes
      in PbB between 1988-1994 and 1999-2002. We analyzed data from the National Health
      and Nutrition Examination Survey (NHANES) III (n=10,755) and NHANES 1999-2002
      (n=8013). In 1999-2002, about 91.7% of study children had detectable levels of
      lead in the blood. Among them, 7.3%, 2.8%, and 1.0% children and adolescents aged
      1-5, 6-11, and 12-21 years, respectively, had PbB between 5 and 9.9 microg/dl.
      This number translates to approximately 2.4 million individuals. Between 1988
      1994 and 1999-2002, the geometric mean PbB declined from 2.88 to 1.94 microg/dl
      in children 1-5 years, 1.80 to 1.36 microg/dl in children 6-11 years, and 1.24
      1.02 microg/dl in children and adolescents 12-21 years of age. Also, the
      prevalence of PbB >or=5 microg/dl declined from 25.7% to 8.8%, 12.8% to 3.0%, and
      7.5% to 1.2% in these age groups, respectively.A substantial proportion of
      children may be at risk for adverse health effects from lead exposure below 10
      microg/dl and a large number of children will be classified as having elevated
      PbB if 5 microg/dl is considered the threshold. Significant public health
      resources will have to be mobilized for intervention, screening, and case
      management of these children.

PMID- 18339370
TI  - A dopamine mechanism is implied in the acquisition and expression of amphetamine
      and stress-induced effects observed in the lymphocyte subpopulations.
AB  - Drugs of abuse and stress are associated with changes in circulating cell
      populations and reductions in cell-mediated immune responses. The main goal of
      this study was to determine the influence of repeated and acute d-amphetamine
      treatments on the foot-shock stress-induced effects on the peripheral lymphocyte
      subpopulations, and the involvement of a dopamine mechanism in the development
      and expression of this phenomenon. Wistar rats received an acute (5 mg/kg/day
      i.p.) or a repeated (2 mg/kg/day i.p. during 9 days) amphetamine treatment, and
      were exposed to a foot-shock stress (1 mA, 3 s) 4 days after the last amphetamine
      injection. Another group was administered with haloperidol (1 mg/kg/day i.p.) 15
      min previous to each daily amphetamine injection or previous to the foot-shock
      stress session. Then, blood cells stained with monoclonal antibodies against CD3
      FITC, CD8-PE and CD4-Cy-Chrome, and against CD161a-FITC, CD3-PE, and CD45RA-Cy
      Crhome, were analyzed by multiparameter flow cytometry. The exposure to a foot
      shock stress induced a decrease in the absolute number of peripheral lymphocytes,
      as well as in CD4+ and CD8+ T-cells and B-cells in acute and repeatedly
      amphetamine-treated rats, whereas the NK-cell population remained unchanged.
      Haloperidol administration previous to each drug administration or the foot-shock
      stress session reversed these effects. This study provides strong evidence that
      dopamine can play a more general role in the influence of amphetamine on the
      stress-induced effects on the lymphocyte subsets.

PMID- 18339371
TI  - Memantine enhances the inhibitory effects of naltrexone on ethanol consumption.
AB  - Effects of the opioid receptor antagonist naltrexone (0.1; 0.3; 1.0 mg/kg i.p.)
      on operant ethanol self-administration alone and in combination with the non
      competitive NMDA antagonist memantine (0.5 and 1 mg/kg, i.p.) were studied in
      rats. Acute administration of naltrexone (0.1; 0.3; 1.0 mg/kg i.p.) inhibited
      ethanol self-administration in a dose-dependent manner. Memantine (1.0 mg/kg)
      significantly enhanced the effects of naltrexone at 0.1 mg/kg, failing per se to
      inhibit ethanol consumption. Thus, low, sub-effective dose of memantine in
      combination with low doses of naltrexone blocked the reinforcing properties of
      ethanol in rats. It is suggested that the combination of sub-effective doses of
      memantine and naltrexone may have therapeutic value in the treatment of
      alcoholism particularly in a subgroup of alcoholic patients who have high
      sensitivity to the adverse side effects of naltrexone.

PMID- 18339372
TI  - Glucocorticoid antagonists in neuropsychiatric [corrected] disorders.
AB  - Neuropsychiatric disorders often involve considerable psychological stress and
      elevated cortisol activity. Glucocorticoid receptors have relatively low affinity
      for cortisol and are found distributed throughout the brain, particularly in the
      frontal cortex and hippocampus. In recent years, glucocorticoid receptors
      antagonists have been actively studied in both animal models of several disorders
      as well as a potential treatment in specific types of neuropsychiatric patients.
      Data from these various studies are reviewed with an emphasis on seven clinical
      disorders or problems: major depression with psychotic features, bipolar
      disorder, schizophrenia, cognitive disorders, (e.g., Alzheimer's disease and mild
      cognitive impairment), cognitive side effects of electroconvulsive therapy, and
      weight gain with atypical antipsychotic agents. Potential benefits and
      limitations are discussed.

PMID- 18339373
TI  - The significance of glucocorticoid pulsatility.
AB  - Glucocorticoids are secreted in discrete pulses resulting in an ultradian rhythm
      in all species that have been studied. In the rat there is an approximately
      hourly rhythm of corticosterone secretion, which appears to be regulated by
      alternating activation and inhibition of the HPA axis. At the level of signal
      transduction, the response to these pulses of corticosterone is determined by its
      dynamic interaction with the two transcription factors--the glucocorticoid and
      mineralocorticoid receptors. While the mineralocorticoid receptor remains
      activated throughout the ultradian cycle, the glucocorticoid receptor shows a
      phasic response to each individual pulse of corticosterone. This phasic response
      is regulated by an intranuclear proteasome-dependent rapid downregulation of the
      activated glucocorticoid receptor.

PMID- 18339374
TI  - Role of chromosome 1 pericentric heterochromatin (1q) in pathogenesis of
      myelodysplastic syndromes: report of 2 new cases.
AB  - Chromosome 1 pericentromeric heterochromatin (1q) has been shown to play an
      important role in the pathogenesis of non-Hodgkin lymphoma and multiple myeloma.
      Myelodysplastic syndrome (MDS) results from marrow failure in two or more cell
      lineages. Although trisomy 1q has been reported in MDS, it is usually present
      with additional common abnormalities such as trisomy 8, monosomy 5 or monosomy 7,
      leading to speculation that 1q abnormalities are mostly secondary events
      representing clonal evolution. We report two cases of MDS in which consistent
      involvement of 1q heterochromatin is seen as the primary clonal abnormality. Both
      patients presented with fatigue and pancytopenia. Based on the published reports
      and our cases, we propose that the 1q heterochromatin plays a vital role in the
      pathophysiology of MDS. Abnormalities involving 1q result in aberrant
      heterochromatin/euchromatin junctions, leading to gene dosage abnormalities.
      Further studies of 1q abnormalities in MDS might provide specific insights as to
      the exact role of the excess 1q heterochromatin in the etiology of MDS.

PMID- 18339375
TI  - Antioxidant capacity contributes to protection of ketone bodies against oxidative
      damage induced during hypoglycemic conditions.
AB  - Ketone bodies play a key role in mammalian energy metabolism during the suckling
      period. Normally ketone bodies' blood concentration during adulthood is very low,
      although it can rise during starvation, an exogenous infusion or a ketogenic
      diet. Whenever ketone bodies' levels increase, their oxidation in the brain
      rises. For this reason they have been used as protective molecules against
      refractory epilepsy and in experimental models of ischemia and excitotoxicity.
      The mechanisms underlying the protective effect of these compounds are not
      completely understood. Here, we studied a possible antioxidant capacity of ketone
      bodies and whether it contributes to the protection against oxidative damage
      induced during hypoglycemia. We report for the first time the scavenging capacity
      of the ketone bodies, acetoacetate (AcAc) and both the physiological and non
      physiological isomers of beta-hydroxybutyrate (D- and L-BHB, respectively), for
      diverse reactive oxygen species (ROS). Hydroxyl radicals (.OH) were effectively
      scavenged by D- and L-BHB. In addition, the three ketone bodies were able to
      reduce cell death and ROS production induced by the glycolysis inhibitor,
      iodoacetate (IOA), while only D-BHB and AcAc prevented neuronal ATP decline.
      Finally, in an in vivo model of insulin-induced hypoglycemia, the administration
      of D- or L-BHB, but not of AcAc, was able to prevent the hypoglycemia-induced
      increase in lipid peroxidation in the rat hippocampus. Our data suggest that the
      antioxidant capacity contributes to protection of ketone bodies against oxidative
      damage in in vitro and in vivo models associated with free radical production and
      energy impairment.

PMID- 18339376
TI  - Fibroids and infertility: an updated systematic review of the evidence.
AB  - OBJECTIVE: To investigate the effect of fibroids on fertility and of myomectomy
      in improving outcomes. DESIGN: Systematic literature review and meta-analysis of
      existing controlled studies. SETTING: Private center for Reproductive
      endocrinology and infertility. PATIENT(S): Women with fibroids and infertility.
      INTERVENTION(S): A systematic literature review, raw data extraction and data
      analysis. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate, spontaneous abortion
      rate, ongoing pregnancy/live birth rate, implantation rate, and preterm delivery
      rate in women with and without fibroids, and in women who underwent myomectomy.
      RESULT(S): Women with subserosal fibroids had no differences in their fertility
      outcomes compared with infertile controls with no myomas, and myomectomy did not
      change these outcomes compared with women with fibroids in situ. Women with
      intramural fibroids appear to have decreased fertility and increased pregnancy
      loss compared with women without such tumors, but study quality is poor.
      Myomectomy does not significantly increase the clinical pregnancy and live birth
      rates, but the data are scarce. Fibroids with a submucosal component led to
      decreased clinical pregnancy and implantation rates compared with infertile
      control subjects. Removal of submucous myomas appears likely to improve
      fertility. CONCLUSION(S): Fertility outcomes are decreased in women with
      submucosal fibroids, and removal seems to confer benefit. Subserosal fibroids do
      not affect fertility outcomes, and removal does not confer benefit. Intramural
      fibroids appear to decrease fertility, but the results of therapy are unclear.
      More high-quality studies need to be directed toward the value of myomectomy for
      intramural fibroids, focusing on issues such as size, number, and proximity to
      the endometrium.

PMID- 18339377
TI  - Oral contraceptive pretreatment in women undergoing controlled ovarian
      stimulation in ganirelix acetate cycles may, for a subset of patients, be
      associated with low serum luteinizing hormone levels, reduced ovarian response to
      gonadotropins, and early pregnancy loss.
AB  - Oral contraceptive pretreatment facilitated scheduling of pure FSH/GnRH
      antagonist cycles but in a small subset of patients was associated with low serum
      LH levels, reduced ovarian response, and early pregnancy loss. Supplementation
      with LH could be examined as a possible way to improve cycle outcome.

PMID- 18339378
TI  - A case of successful laparoscopic resection of adrenal gland endometriosis.
AB  - OBJECTIVE: To present a case of successful laparoscopic resection of adrenal
      endometriosis. DESIGN: Case report. SETTING: University Hospital. PATIENT(S):
      Forty-eight-year-old woman with left-sided abdominal and flank pain.
      INTERVENTION(S): Laparoscopic radical adrenalectomy. MAIN OUTCOME MEASURE(S):
      Diagnosis and surgical approach to adrenal endometriosis. RESULT(S): There have
      been two case reports of adrenal endometriosis. Based on a search of Medline and
      Google for "adrenal endometriosis," this is the first known successful
      laparoscopic resection of adrenal endometriosis. CONCLUSION(S): We report the
      first case of successful laparoscopic adrenalectomy for the treatment of
      endometriosis.

PMID- 18339379
TI  - Long-term safety and tolerability of flutamide for the treatment of hirsutism.
AB  - OBJECTIVE: To evaluate the long-term safety and tolerability of flutamide therapy
      for hirsutism. DESIGN: Prospective observational study. SETTING: Gynecology
      department in a teaching hospital. PATIENT(S): Hyperandrogenic women presenting
      for hirsutism treatment were followed between January 2000 and January 2007.
      INTERVENTION(S): Women received flutamide 250 mg/day alone (n = 27) or combined
      with a fixed dose of an oral contraceptive containing 0.020 mg of ethinyl
      estradiol (EE) and 0.15 mg of desogestrel (n = 56). MAIN OUTCOME MEASURE(S):
      Adverse events, safety, tolerability and efficacy were assessed every 6 months
      during the follow-up. Liver and lipid profiles were also recorded. RESULT(S):
      Patients under flutamide therapy showed, compared with basal values, a
      significant progressive decrease in hirsutism scores after 6 months of treatment
      with a maximum effect at 12 months that was maintained during the 84 months of
      follow-up. A total of 40.96% women presented one or more adverse effects during
      the follow-up; 33.73% showed at least one adverse effect possibly related with
      the study drug, and 24.09% withdrew from the study because of adverse effects.
      During the follow-up, as many as 59% of patients abandoned the study.
      CONCLUSION(S): Flutamide is very effective for hirsutism treatment; however,
      adverse effects are very frequent and associated with low long-term compliance.

PMID- 18339380
TI  - Determination of Poly (ADP-ribose) polymerase (PARP) homologues in human
      ejaculated sperm and its correlation with sperm maturation.
AB  - OBJECTIVES: To investigate the presence of Poly (ADP-ribose) polymerase (PARP)
      and evaluate its function in ejaculated spermatozoa. DESIGN: Experimental study.
      SETTING: Reproductive Research Center. PATIENT(S): Semen specimens from 18
      healthy donors and 12 infertile males. INTERVENTION(S): Ejaculated spermatozoa
      were subjected to sperm fractionation with a double-layer density gradient,
      protein extraction, detection, immunoblotting, and mass spectrometry. Semen
      samples were exposed to PARP inducer staurosporine, or hydrogen peroxide with or
      without PARP inhibitor 3-aminobenzimide. Annexin V assay was examined for
      apoptosis by flow cytometry. RESULT(S): We detected approximately 75 kDa,
      approximately 63 kDa, and approximately 60 kDa PARP homologues on the immunoblot
      of mature and immature sperm fraction isolated from human ejaculate, which were
      identified as PARP-1 ( approximately 75 kDa), PARP-9 ( approximately 63 kDa), and
      PARP-2 ( approximately 60 kDa), respectively. Western blot analysis showed a
      positive correlation between the amount of PARP protein and sperm maturity. PARP
      proteins (75 kDa, 63 kDa, and 60 kDa) were evaluated after inducing apoptosis by
      hydrogen peroxide and staurosporine exposure. CONCLUSION(S): PARP-2 may have a
      role in prevention of oxygen species/oxidative stress and chemical
      (staurosporine)-induced sperm cell apoptosis. The presence of the PARP homologue,
      that is, PARP-1 ( approximately 75 kDa), suggests its role in preventing damage
      of mature sperm. Additional studies are needed to delineate the role of PARP-9 in
      sperm physiology. The results from our study indicate an active role for PARPs in
      sperm cell physiology in preventing apoptosis.

PMID- 18339381
TI  - Conservative management of cervical ectopic pregnancy.
AB  - OBJECTIVE: To evaluate the safety and efficacy of a minimally invasive approach
      in the management of cervical ectopic pregnancies. DESIGN: Retrospective case
      series. SETTING: University tertiary care hospital. PATIENT(S): Twenty-four women
      diagnosed with cervical ectopic pregnancy managed conservatively.
      INTERVENTION(S): Systemic methotrexate alone or combined with ultrasound-guided
      fetal intracardiac injection of potassium chloride. MAIN OUTCOME MEASURE(S):
      Reduction in hysterectomy rate, incidence of serious complications, and necessity
      for further intervention. RESULT(S): Conservative management of cervical ectopic
      pregnancy was successful in preventing the need for hysterectomy in all patients
      in our study. In two patients with a heterotopic gestation the intrauterine
      pregnancy could successfully be salvaged. Four patients experienced morbidity
      that required additional interventions. CONCLUSION(S): Most cervical ectopic
      pregnancies can be safely managed in a minimally invasive manner.

PMID- 18339382
TI  - Sequence alterations in the YBX2 gene are associated with male factor
      infertility.
AB  - OBJECTIVE: To investigate YBX2 gene alterations in men with severe defects in
      spermatogenesis, including azoospermia or severe oligozoospermia, and protamine
      deregulation. MSY2 has been identified as a central component in the regulation
      of spermatogenesis in mice, but the potential role of its human orthologue, YBX2
      or "Contrin," in human infertility is not known. DESIGN: A prospective cohort
      study. SETTING: University infertility clinic and associated research laboratory.
      PATIENT(S): A total of 288 men were evaluated. Diagnoses were made of complete
      azoospermia, severe oligozoospermia, and protamine deregulation, or men were of
      known paternity. INTERVENTION(S): Deoxyribonucleic acid (from peripheral blood)
      and semen samples were collected and analyzed for gene mutations and semen
      parameters respectively. MAIN OUTCOME MEASURE(S): YBX2 gene alterations.
      RESULT(S): YBX2 sequence analysis revealed 15 polymorphic sites, of which seven
      polymorphisms were present at a statistically higher frequency in one or both of
      the patient populations than in controls. Of these seven, two resulted in an
      amino acid substitution in the highly conserved cold shock domain and one
      resulted in a highly significant synonymous change in exon 8 of infertile
      patients. The frequency of single nucleotide polymorphisms was significantly
      elevated in patients with infertility, particularly in men with abnormal
      protamine expression. CONCLUSION(S): These data indicate a significant
      association between gene alterations in the YBX2 gene and abnormal
      spermatogenesis in humans, including a potential role in altering protamine
      expression, and implicate YBX2 gene alterations as a potential cause of male
      factor infertility.

PMID- 18339383
TI  - Endometrioma and oocyte retrieval-induced pelvic abscess: a clinical concern or
      an exceptional complication?
AB  - The authors evaluated the risk of developing a pelvic abscess in a series of 214
      in vitro fertilization cycles that were performed in women with endometriomas.
      This complication was never recorded, indicating that its risk is very low (0.0;
      95% confidence interval, 0.0-1.7%).

PMID- 18339384
TI  - Cost-saving treatment strategies in in vitro fertilization: a combined economic
      evaluation of two large randomized clinical trials comparing highly purified
      human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.
AB  - OBJECTIVE: To assess the cost-effectiveness of two gonadotropin treatments that
      are available in the United Kingdom in light of limited public funding and the
      fundamental role of costs in IVF treatment decisions. DESIGN: An economic
      evaluation based on two large randomized clinical trials in IVF patients using a
      simulation model. SETTING: Fifty-three fertility clinics in 13 European countries
      and Israel. PATIENT(S): Women indicated for treatment with IVF (N = 986), aged 18
      38, participating in double-blind, randomized controlled trials. INTERVENTION(S):
      Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha
      (rFSH, Gonal-F). MAIN OUTCOME MEASURE(S): Cost per IVF cycle and cost per live
      birth for HP-hMG and rFSH alpha. RESULT(S): HP-hMG was more effective and less
      costly versus rFSH for both IVF cost per live birth and for IVF cost per baby
      (incremental cost-effectiveness ratio was negative). The mean costs per IVF
      treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI],
      2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds),
      respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows
      one additional cycle to be delivered for every 9.5 cycles. CONCLUSION(S):
      Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom.
      Gonadotropin costs should be considered alongside live-birth rates to optimize
      outcomes using scarce health-care resources.

PMID- 18339386
TI  - Correlates between hyperinsulinism and hyperandrogenemia?

PMID- 18339387
TI  - Autoimmune response to Chlamydia trachomatis infection and in vitro fertilization
      outcome.
AB  - This observational study was conducted in 235 patients undergoing IVF who had a
      cervical swab positive for Chlamydia trachomatis and who underwent antibiotic
      treatment until a negative cervical swab before IVF attempt. After oocyte
      retrieval, follicular fluids of 109 patients out of 228 still showed the presence
      of IgA antichlamydia antibodies and a significantly lower pregnancy and
      implantation rate; therefore we conclude that patients should undergo IVF
      procedure after serum antichlamydia IgA tests negative.

PMID- 18339388
TI  - Pregnancy after uterine fibroid embolization: follow-up of 100 patients embolized
      using tris-acryl gelatin microspheres.
AB  - OBJECTIVE: To evaluate pregnancies in women who had previously undergone uterine
      fibroid embolization. DESIGN: Prospective study. SETTING: A city hospital in
      Spain. PATIENT(S): A cohort of 100 uterine fibroid embolization patients, 57 of
      whom wished to preserve their fertility. INTERVENTION(S): Uterine arteries were
      embolized by using 500-1,200 microm tris-acryl gelatin microspheres. After
      intervention, patient follow-up was performed at 1 week, 3 months, 6 months, and
      yearly. MAIN OUTCOME MEASURE(S): The number of pregnancies and course of
      pregnancy. RESULT(S): Eleven pregnancies in 10 women (19.2%). The pregnancies
      resulted in 8 live births, including 4 normal and 4 cesarean deliveries. Early
      miscarriage occurred in 3 cases (2 patients). None of the 8 newborns was a low
      birth weight infant, and gestation lasted >or=37 weeks in all the patients,
      except for 1 case of a macrosomic fetus delivered at 33 weeks. There were no
      cases of abnormal placental implantation. CONCLUSION(S): Despite the small sample
      size, uterine artery embolization appears to be viable in young women who still
      want to become pregnant. Larger series and studies comparing uterine fibroid
      embolization and myomectomy are needed.

PMID- 18339389
TI  - The F.A.S.T.E.R. trial. Focused assessment by sonography in trauma during
      emergency retrieval: a feasibility study.
AB  - INTRODUCTION: This feasibility study aimed to establish if retrieval physicians
      can overcome the transport environment and obtain F.A.S.T. (focused assessment by
      sonography in trauma) images of suitable quality during patient retrieval in
      rotary wing aircraft such that diagnostic interpretation of free intra-abdominal
      fluid or pericardial fluid would be possible. MATERIALS AND METHODS: During a 6
      month trial period, one of three retrieval physicians attempted to obtain the
      standard four quadrant F.A.S.T. views using a portable ultrasound on patients
      they retrieved. Ultrasound images were obtained whilst in-flight in a rotary wing
      aircraft. Image adequacy was assessed by the retrieval physician and by an
      independent blinded physician using strict clinical criteria. RESULTS: Thirty
      eight patients were enrolled. Thirty-six patients had a complete F.A.S.T. scan
      attempted whilst a further two patients had their abdominal quadrants scanned
      without a pericardial view being attempted. Independent blinded physician review
      of scans agreed with the scanning retrieval physician that images were adequate
      for showing the F.A.S.T. quadrants appropriately in 143 of 150 quadrants imaged
      and inadequate in two. Blinded physician review disagreed with scanning physician
      regarding adequacy of image in 5 of 150 quadrants imaged. Scanning physicians
      were happy with adequacy of the view in all F.A.S.T. quadrants in 34 of the 36
      patients in whom a complete F.A.S.T. was performed. Blinded physician review
      agreed in 30 of those cases. DISCUSSION: The physicians performing the F.A.S.T.
      examination, all incorporate ultrasound into their daily clinical practice
      thereby maintaining their skill level. This is likely to contribute to the high
      level of view adequacy. Independent blinded image review controlled for bias
      regarding view adequacy. Disagreement between scanning physician and reviewing
      physician assessment of view adequacy in 5 of the 150 views obtained is likely to
      relate to the difficulties in interpreting still ultrasound images, compared to
      interpreting real time images at point-of-care. There were no machine
      limitations. CONCLUSION: This study demonstrates that it is possible for critical
      care retrieval physicians to obtain adequate ultrasound F.A.S.T. images on
      patients using a portable ultrasound machine en-route to definitive care, in a
      rotary wing aircraft.

PMID- 18339390
TI  - The role of psychosocial, behavioural and emotional factors on self-reported
      major injuries in Brazilian adolescents: a case-control study.
AB  - INTRODUCTION: The objective of this research was to investigate the
      sociodemographic, psychosocial, behavioural and emotional risk factors associated
      with self-reported major injuries. METHODS: A case-control study, nested in a two
      stage survey, was carried out in two cities of the Distrito Federal, Brazil.
      Cases were defined as subjects who reported an event resulting in injury or
      physical harm to the person, about which a hospital was visited or a doctor
      consulted (major injury), during the period of 6 months preceding the interview.
      Controls (n=640) were matched to cases (n=231) based on sex and neighbourhood.
      Information on determinants of injuries was collected by self-completed
      questionnaires and included sociodemographic, psychosocial, behavioural and
      emotional variables. Data analysis used conditional logistic regression models.
      RESULTS: Controlling for social support and pro-social behaviour, adolescents
      reporting "abnormal" behaviour and emotional problems had more than three times
      the chance of reporting a major injury compared to "normal" status adolescents
      (OR=3.65, 95%CI=1.83-7.32). DISCUSSION: The findings of this study suggest that
      preventive strategies, while addressing the broader community and environmental
      risk factors for injuries, need to address the behavioural and emotional factors
      associated with these injuries.

PMID- 18339391
TI  - Acceptance of evidence-based reproductive health care among postgraduate
      specialist trainees in Nigeria.
AB  - OBJECTIVE: To assess the perception and practice of evidence-based reproductive
      health care among Nigerian postgraduate specialist trainee doctors. METHOD: A
      questionnaire survey of 326 Nigerian postgraduate specialist trainee doctors
      involved in reproductive health care was undertaken during training workshops on
      evidence-based medicine. RESULTS: Most respondents were familiar with evidence
      based medicine (96.6%) and agreed that it would improve patient care (95.1%).
      Only 38.3% had ever received training on evidence-based medicine. Awareness and
      utilization of resources for evidence-based medicine were low; only 18.7% and
      28.2% had ever used the Cochrane Library or the WHO Reproductive Health Library,
      respectively. Understanding of technical terms related to evidence-based medicine
      was poor. Lack of access to evidence was the most common constraint to the
      practice of evidence-based reproductive health care. CONCLUSION: Nigerian
      postgraduate specialist trainee doctors are positively disposed to evidence-based
      reproductive health care but their understanding of the principles of evidence
      based practice is inadequate.

PMID- 18339392
TI  - HPV vaccination and screening to eliminate cervical cancer.

PMID- 18339393
TI  - Application of solid-phase microextraction for determination of pyrethroids in
      groundwater using liquid chromatography with post-column photochemically induced
      fluorimetry derivatization and fluorescence detection.
AB  - Solid-phase microextraction (SPME) is a rapid and simple analytical technique
      which uses coated fused-silica fibers to extract analytes from aqueous samples.
      This study develops a method of SPME analysis for seven pyrethroids, including
      fenpropathrin, lambda-cyhalothrin, deltamethrin, fenvalerate, permethrin, tau
      fluvalinate and bifenthrin in groundwater samples using high performance liquid
      chromatography combined with post-column photochemically induced fluorimetry
      derivatization and fluorescence detection (SPME-LC-PIF-FD). To perform the SPME,
      a 60 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber was used for the
      extraction of the pesticides from groundwater samples. The main factors affecting
      the SPME process, such as extraction time, stirring rate, extraction temperature,
      pH and the desorption process were studied. The use of photochemically induced
      fluorescence for detection improved sensitivity and selectivity. The limits of
      quantification (LOQs) obtained in the matrix, with respect to EURACHEM Guidance,
      varied between 0.03 and 0.075 microgL(-1). Relative recoveries ranged from 92 to
      109% and relative standard deviations values ranged from 2 to 9%.

PMID- 18339394
TI  - Stationary phase retention and preliminary application of a spiral disk assembly
      designed for high-speed counter-current chromatography.
AB  - A spiral disk assembly composed of five single-channel units was designed for
      high-speed counter-current chromatography (HSCCC). The retention of different
      solvent systems ranging from moderately polar to polar organic-aqueous systems to
      aqueous two-phase systems (ATPs) was investigated under different elution modes.
      The results indicated that the spiral disk assembly can produce excellent
      retention of stationary phase for moderately polar organic-aqueous solvent
      systems, such as chloroform-methanol-water (4:3:2) and hexane-ethyl acetate
      methanol-water (1:1:1:1) by pumping lower mobile phase from head (H) to tail (T),
      and upper mobile phase from tail (T) to head (H) even at a high flow-rate (8
      mL/min, Sf>70%), regardless of whether the inlet is at the inner or outer
      terminal of the channel. This makes it possible for fast analysis of some small
      molecular compounds. This has been proved in the separation of mixtures of three
      flavones, including isorhamnetin, kaempferol, and quercetin. The spiral disk
      assembly can also provide satisfactory retention for polar to ATPS such as 1
      butanol-acetic acid-water (4:1:5) (<3 mL/min, Sf>70%), 12.5% poly(ethylene
      glycol) (PEG) 1000-12.5% K2HPO4-75% water (< or =1 mL/min, Sf>70%) and 4% PEG
      8000-5% Dextran T500-91% water (< or =0.5 mL/min, Sf>50%) by pumping lower mobile
      phase from inner terminal (I) to outer terminal (O), and upper mobile phase from
      outer terminal (O) to inner terminal (I) at a low flow-rate, while this is not
      possible with the multilayer coil column. Acceptable resolutions were achieved
      when it was used for the separation of peptides such as Leu-Tyr and Val-Tyr, and
      proteins including cytochrome c and myoglobin, lysozyme and myoglobin, and fresh
      chicken egg-white proteins.

PMID- 18339395
TI  - Development and optimization of a system for comprehensive two-dimensional liquid
      chromatography with UV and mass spectrometric detection for the separation of
      complex samples by multi-step gradient elution.
AB  - Comprehensive two-dimensional liquid chromatography (LC x LC) is a powerful tool
      for the separation of complex biological samples. This technique offers the
      advantage of simplified automation and greater reproducibility in a shorter
      analysis time than off-line two-dimensional separation systems. In the present
      study, an LC x LC system is developed enabling simultaneous UV and MS detection,
      and which can be easily converted to a conventional reversed-phase LC-UV/MS
      system. In LC x LC, a 60-min reversed-phase LC separation with a linear solvent
      gradient in the first dimension is coupled to a second-dimension separation on a
      mixed-mode cation-exchange/reversed-phase column with a modulation time of 60s.
      The isocratic separation in the second-dimension column is optimized by the use
      of a multi-step gradient where the organic and the ionic modifier are varied
      independently. Intraday (n=3) and interday (n=4) variability of the retention
      times were evaluated with the complete system and found to be 0.5% and 0.7%,
      respectively. Good linearity was observed in calibration curves for three
      different compounds varying in polarity.

PMID- 18339396
TI  - Comparison of dual solvent-stir bars microextraction and U-shaped hollow fiber
      liquid phase microextraction for the analysis of Sudan dyes in food samples by
      high-performance liquid chromatography-ultraviolet/mass spectrometry.
AB  - Two sample preparation methods, dual solvent-stir bars microextraction (DSSBME)
      and U-shaped hollow fiber-liquid phase microextraction (U-shaped HF-LPME), are
      proposed and critically compared for high-performance liquid chromatography
      (HPLC)-ultraviolet (UV)/mass spectrometry (MS) analysis of Sudan dyes in this
      paper. In DSSBME, the organic solvent was confined to a pair of hollow fiber
      membrane fixed on a stir bar, which can stir by itself, while the hollow fiber in
      U-shaped HF-LPME was fixed by two microsyringes. The significant factors
      affecting the microextraction of Sudan dyes in both microextraction techniques
      have been examined and no obvious difference in the effect of extraction solvent,
      pH and salt concentration on the extraction efficiency of Sudan dyes was observed
      except extraction time and stirring speed. Both microextraction techniques were
      similar in terms of analytical performance from aqueous solutions (LODs ranged
      from 0.09 to 0.95 microgL(-1) by HPLC-UV and 2.5-6.2 microgL(-1) by HPLC-MS; the
      absolute LODs ranged from 0.9 to 11.25 pg by HPLC-UV and 5-21.2 pg by HPLC-MS),
      however, DSSBME was more stable (lower stirring speed required), less sample
      consuming and much shorter time required to reach extraction equilibrium; while U
      shaped HF-LPME was easier to operate and no more special device required. The two
      microextraction techniques combined with HPLC-UV/MS were successfully applied to
      the analysis of real samples including strawberry sauce, capsicum oil, salted
      egg, and two kinds of chilli sauce. Although the LODs of HPLC-UV are lower than
      that of HPLC-MS by a factor of 10 in this work, the absolute LODs for both HPLC
      UV and HPLC-MS are comparable. HPLC-UV cannot identify the suspicious peaks at
      the same retention time as that of Sudan II and III in salted egg, while HPLC-MS
      can give exact information of Sudan I-IV in real sample analysis and is more
      reliable. The sensitivity of HPLC-MS is enough for real sample analysis.

PMID- 18339397
TI  - Comparison of microdialysis with solid-phase microextraction for in vitro and in
      vivo studies.
AB  - Microdialysis (MD) and solid-phase microextraction (SPME) methods have been
      developed and compared through in vitro and in vivo studies. For in vitro study,
      both methods offered accurate and precise results for complex sample matrices by
      standard addition method. Compared to MD, the fully automated SPME procedure
      offered several advantages including high-throughput and more efficient sampling,
      less labor intensity, and capability for batch analysis. For in vivo study,
      although both techniques provided sampling with minimal perturbation to the
      system under study, SPME was more sensitive, precise and accurate, suitable for
      field sampling and had a wider application than MD. It demonstrated that SPME has
      the potential to replace MD for in vivo study.

PMID- 18339398
TI  - Errors involved in the existing B-term expressions for the longitudinal diffusion
      in fully porous chromatographic media Part II: experimental data in packed
      columns and surface diffusion measurements.
AB  - Peak parking experiments have been performed on three RP-HPLC different columns,
      using two different components and a variable mobile phase composition. The aim
      of the study was to investigate whether the B-term diffusion expressions
      currently used in the literature (which are all Knox-type models) should be
      replaced by the effective diffusion expressions that have been developed in the
      frame of the effective medium theory (EMT). Although the EMT-expressions are not
      fully accurate either (the mathematics of the complex interactions between
      different diffusion zones that are in close contact are too demanding to catch
      them in an exact analytical expression), they at least are physically sound and
      do not violate Maxwell's basic law of diffusion. Further they also provide a much
      better approximation of the numerically calculated effective diffusivity in the
      theoretical test situation considered in part I. The present study shows that the
      values of the surface or stationary phase diffusion coefficient that are derived
      from peak parking models can depend heavily on the employed B-term model. The EMT
      based B-term expressions lead to values of the surface diffusion coefficient that
      vary much less strongly with the phase retention factor than if one of the Knox
      type models is used to analyze the data. This implies that, since all peak
      parking experiments that have been performed in the past have all been
      interpreted with a Knox-type model, the conclusions that have been drawn from
      these studies should all be moderated or at least revisited.

PMID- 18339399
TI  - Small GTP-binding proteins and their regulators in cardiac hypertrophy.
AB  - Small GTP-binding proteins (small G proteins) act as GDP-GTP-regulated molecular
      switches and are activated by guanine nucleotide exchange factors (GEFs) in
      response to diverse extracellular stimuli. During this last decade, numerous
      molecular and cellular studies, as well as genetically-modified animal models,
      have highlighted the role of small G proteins in the regulation of cardiac
      hypertrophy. The growing interest in small G protein signalling comes from the
      fact that chronic hypertrophic response is considered maladaptive and predisposes
      individuals to heart failure. Although some of the hypertrophic signalling
      pathways involving small G proteins have now been identified, a central question
      deals with the identity of the GEFs that modulate small G protein activation in
      the context of cardiac hypertrophy. Here, we discuss the precise regulation of
      Ras and Rho subfamilies of GTPases by GEFs and other regulatory proteins during
      cardiac hypertrophy. In addition, we summarize recent published data, mainly
      those describing the role of small G proteins in the development of myocardial
      hypertrophy and we further present the importance of their downstream effectors
      in myocardial remodelling.

PMID- 18339400
TI  - The C-terminal region of the meiosis-specific protein kinase Ime2 mediates
      protein instability and is required for normal spore formation in budding yeast.
AB  - The cyclin-dependent kinase Cdk1 and the related kinase Ime2 act in concert to
      trigger progression of the meiotic cell cycle in the yeast Saccharomyces
      cerevisiae. These kinases share several functions and substrates during meiosis,
      but their regulation seems to be clearly different. In contrast to Cdk1, no
      cyclin seems to be involved in the regulation of Ime2 activity. Ime2 is a highly
      unstable protein, and we aimed to elucidate the relevance of Ime2 instability. We
      first determined the sequence elements required for Ime2 instability by
      constructing a set of deletions in the IME2 gene. None of the small deletions in
      Ime2 affected its instability, but deletion of a 241 amino acid C-terminal region
      resulted in a highly stabilized protein. Thus, the C-terminal domain of Ime2 is
      important for mediating protein instability. The stabilized, truncated Ime2
      protein is highly active in vivo. Replacement of the IME2 gene with the truncated
      IME2DeltaC241 in diploid strains did not interfere with meiotic nuclear
      divisions, but caused abnormalities in spore formation, as manifested by the
      appearance of many asci with a reduced spore number such as triads and dyads. The
      truncated Ime2 caused a reduction of spore number in a dominant manner. We
      conclude that downregulation of Ime2 kinase activity mediated by the C-terminal
      domain is required for the efficient production of normal four-spore asci. Our
      data suggest a role for Ime2 in spore number control in S. cerevisiae.

PMID- 18339401
TI  - Subtle changes in peptide conformation profoundly affect recognition of the non
      classical MHC class I molecule HLA-E by the CD94-NKG2 natural killer cell
      receptors.
AB  - Human leukocyte antigen (HLA)-E is a non-classical major histocompatibility
      complex class I molecule that binds peptides derived from the leader sequences of
      other HLA class I molecules. Natural killer cell recognition of these HLA-E
      molecules, via the CD94-NKG2 natural killer family, represents a central innate
      mechanism for monitoring major histocompatibility complex expression levels
      within a cell. The leader sequence-derived peptides bound to HLA-E exhibit very
      limited polymorphism, yet subtle differences affect the recognition of HLA-E by
      the CD94-NKG2 receptors. To better understand the basis for this peptide-specific
      recognition, we determined the structure of HLA-E in complex with two leader
      peptides, namely, HLA-Cw*07 (VMAPRALLL), which is poorly recognised by CD94-NKG2
      receptors, and HLA-G*01 (VMAPRTLFL), a high-affinity ligand of CD94-NKG2
      receptors. A comparison of these structures, both of which were determined to 2.5
      A resolution, revealed that allotypic variations in the bound leader sequences do
      not result in conformational changes in the HLA-E heavy chain, although subtle
      changes in the conformation of the peptide within the binding groove of HLA-E
      were evident. Accordingly, our data indicate that the CD94-NKG2 receptors
      interact with HLA-E in a manner that maximises the ability of the receptors to
      discriminate between subtle changes in both the sequence and conformation of
      peptides bound to HLA-E.

PMID- 18339402
TI  - Three-dimensional solution structure and conformational plasticity of the N
      terminal scavenger receptor cysteine-rich domain of human CD5.
AB  - The lymphocyte receptor CD5 influences cell activation by modifying the strength
      of the intracellular response initiated by antigen engagement. Regulation through
      CD5 involves the interaction of one or more of its three scavenger receptor
      cysteine-rich domains present in the extracellular region. Here, we present the
      3D solution structure of a non-glycosylated double mutant of the N-terminal
      domain of human CD5 expressed in Escherichia coli (eCD5d1m), which has enhanced
      solubility compared to the non-glycosylated wild-type (eCD5d1). In common with a
      glycosylated form expressed in Pichia pastoris, the [(15)N,(1)H]-correlation
      spectra of both eCD5d1 and eCD5d1m exhibit non-uniform temperature-dependent
      signal intensities, indicating extensive conformational fluctuations on the micro
      millisecond timescale. Although approximately one half of the signals expected
      for the domain are absent at 298 K, essentially complete resonance assignments
      and a solution structure could be obtained at 318 K. Because of the sparse nature
      of the experimental restraint data and the potentially important contribution of
      conformational exchange to the nuclear Overhauser effect peak intensity, we
      applied inferential structure determination to calculate the eCD5d1m structure.
      The inferential structure determination ensemble has similar features to that
      obtained by traditional simulated annealing methods, but displays superior
      definition and structural quality. The eCD5d1m structure is similar to other
      members of the scavenger receptor cysteine-rich superfamily, but the position of
      the lone alpha helix differs due to interactions with the unique N-terminal
      region of the domain. The availability of an experimentally tractable form of
      CD5d1, together with its 3D structure, provides new tools for further
      investigation of its function within intact CD5.

PMID- 18339403
TI  - A mesoscale model of G1/S phase transition in liver regeneration.
AB  - The liver regenerates and maintains its function and size after injury by
      counterbalancing cell death with compensatory cell division. During liver
      regeneration, injured sites release cytokines, which stimulate normally quiescent
      hepatocytes to re-enter cell division cycle. Using a mesoscale approach, we have
      implemented the first mathematical model that describes cytokine-induced
      dedifferentiation of hepatocytes and the subsequent initiation of DNA synthesis
      (G0/G1 and G1/S phase transitions of the cell cycle). The model accurately
      reproduces experimentally measured kinetics of various signaling intermediates
      and DNA synthesis in hepatocytes for varying degrees of liver damage, in both
      wild type and knockout backgrounds. Liver regeneration is known to be a robust
      process, as liver mass reconstitution still occurs in various knockout mice
      (albeit with different kinetics). We analyze the robustness of the model using
      methods of control analysis. Moreover, we discuss the system's bandpass filtering
      properties and delays, which arise from feedbacks and nested feed-forward loops.

PMID- 18339404
TI  - Origins of the BOLD changes due to synaptic activity at astrocytes abutting
      arteriolar smooth muscle.
AB  - We have recently provided a detailed model that links glutamatergic synaptic
      activity to volume and blood flow changes in nearby arterioles [Bennett, M.R.,
      Farnell, L., Gibson, W.G., 2008. Origin of blood volume change due to
      glutamatergic synaptic activity at astrocytes abutting on arteriolar smooth
      muscle cells. J. Theor. Biol. 250, 172-185]. This neurovascular coupling model is
      used in the present work to predict changes in deoxyhemoglobin (Hbr) in
      capillaries, arterioles, venules and veins due to glutamatergic synaptic activity
      and hence the changes in the blood oxygen level dependent (BOLD) signals recorded
      by functional magnetic resonance imaging. The model provides a quantitative
      account of Hbr changes observed in each of the vascular compartments following
      stimulation of somatosensory cortex and visual cortex and of the BOLD signal
      following stimulation of motor and visual cortex.

PMID- 18339405
TI  - The coherence of the vesicle theory of protein secretion.

PMID- 18339406
TI  - [Craniocerebral gunshot wounds: a study of outcome predictors].
AB  - BACKGROUND AND PURPOSE: A retrospective study about craniocerebral gunshot wounds
      was done to better identify outcome predictors. METHODS: We reported and analyzed
      the clinical and radiological data of 18 patients admitted to Le Kremlin-Bicetre
      institute for a craniocerebral gunshot wound between January 2000 and December
      2005. The Glasgow Outcome Scale (GOS) was used to analyze patient outcome.
      RESULTS: There were 17 men and one woman, mean age 43 years (range 17-84).
      Fifteen patients died, two had a GOS equal to 2 and one GOS equal to 3. There
      were 16 suicides and two murders. All patients with areactive bilateral mydriasis
      and all patients with Glasgow Coma Scale (GCS) less than seven died except one.
      The 10 patients with intraventricular hemorrhage died. The bullet crossed the
      midline for 13 patients and all of them died. None of the patients underwent
      emergency surgery for the treatment of craniocerebral gunshot wounds because of
      low Glasgow Coma Scale. CONCLUSIONS: This study shows some interesting prognosis
      patterns: bilateral areactive mydriasis, GCS less or equal to 7 and bullet
      trajectory (if crossing the midline) are the most important factors predicting a
      fatal outcome.

PMID- 18339407
TI  - Blockade of central vasopressin receptors reduces the cardiovascular response to
      acute stress in freely moving rats.
AB  - To investigate the contribution of central vasopressin receptors to blood
      pressure (BP) and heart rate (HR) response to stress we injected non-peptide
      selective V(1a) (SR49059), V(1b) (SSR149415), V(2) (SR121463) receptor
      antagonists, diazepam or vehicle in the lateral cerebral ventricle of conscious
      freely moving rats stressed by blowing air on their heads for 2 min.
      Cardiovascular effects of stress were evaluated by analyzing maximum increase of
      BP and HR (MAX), latency of maximum response (LAT), integral under BP and HR
      curve (integral), duration of their recovery and spectral parameters of BP and HR
      indicative of increased sympathetic outflow (LF(BP) and LF/HF(HR)). Moreover, the
      increase of serum corticosterone was measured. Exposure to air-jet stress induced
      simultaneous increase in BP and HR followed by gradual decline during recovery
      while LF(BP) oscillation remained increased as well as serum corticosterone
      level. Rats pre-treated with vasopressin receptor antagonists were not sedated
      while diazepam induced sedation that persisted during exposure to stress. V(1a),
      V(1b) and V(2) receptor antagonists applied separately did not modify basal
      values of cardiovascular parameters but prevented the increase in integral(BP).
      In addition, V(1b) and V(2) receptor antagonists reduced BP(MAX) whereas V(1a),
      V(1b) antagonist and diazepam reduced HR(MAX) induced by exposure to air-jet
      stress. All drugs shortened the recovery period, prevented the increase of LF(BP)
      without affecting the increase in serum corticosterone levels. Results indicate
      that vasopressin receptors located within the central nervous system mediate, in
      part, the cardiovascular response to air-jet stress without affecting either the
      neuroendocrine component or inducing sedation. They support the view that the
      V(1b) receptor antagonist may be of potential therapeutic value in reducing
      arterial pressure induced by stress-related disorders.

PMID- 18339408
TI  - Impact of ambiguity and risk on decision making in mild Alzheimer's disease.
AB  - Decisions under ambiguity and decisions under risk are crucial types of decision
      making in daily living at any age. This is the first study assessing these two
      types of decisions in patients with mild dementia of Alzheimer's type (DAT) by
      means of the Iowa Gambling Task (IGT) and a newly developed, Probability
      Associated Gambling (PAG) task. While rules for gains and losses are implicit in
      the IGT, in the PAG task rules are explicit and winning probabilities, which
      change from trial to trial, can be estimated. Results of the IGT indicated that
      DAT patients made more disadvantageous decisions than healthy controls. Patients
      also shifted more frequently among decks, i.e. under ambiguity decisions were
      taken randomly and no advantageous strategy was established over time by DAT
      patients. Thus, not only actual choices but also development of advantageous
      strategies may be revealing about decision making in the IGT. Compared to
      controls, patients demonstrated less advantageous choices in the PAG task as
      well. They gambled more often in the low winning probabilities and less
      frequently in the high probabilities than healthy participants. Patients'
      performance on both tasks correlated with measures of executive functions.
      Findings of the present investigation are consistent with the early pathological
      cerebral changes and related (cognitive, emotional) deficits reported for DAT. As
      suggested by our study, decisions under ambiguity as well as decisions under risk
      are impaired in mild DAT. It may thus be expected that patients with mild DAT
      have difficulties in taking decisions in every-day life situations, both in cases
      of ambiguity (information on probability is missing or conflicting, and the
      expected utility of the different options is incalculable) and in cases of risk
      (outcomes can be predicted by well-defined or estimable probabilities).

PMID- 18339409
TI  - What activates the human mirror neuron system during observation of artificial
      movements: bottom-up visual features or top-down intentions?
AB  - In a recent study we could show that during observation of artificial object
      movements a similar cortical network, including the areas of the so-called human
      mirror neuron system (hMNS), was activated as during the observation of hand
      movements. The present study investigated whether activation of the hMNS during
      the observation of artificial object movements depends more on the visual
      features of the movements (buttom-up), or, by manipulating the task instructions,
      on the intentional goal of an observer (top-down). Using a factorial design we
      recorded the hemodynamic responses in 20 healthy participants while they watched
      arbitrary artificial object movements following two types of movement
      trajectories (smooth vs. discontinuous). In one part of the experiment
      participants had to detect color changes of two objects (color task) and in
      another part they had to judge whether the movement pattern of two objects could
      be performed with human hands (simulation task). We found stronger activation in
      the hMNS during the simulation than during the color task for both types of
      movement trajectories. In contrast, the color task activated the left ventral
      occipital area (human V4). A direct comparison of smooth vs. discontinuous
      movement trajectories revealed significant effects neither in the structures of
      the hMNS nor in human V4. The present findings suggest that it is not a specific
      visual feature, such as a smooth biological movement trajectory, that activates
      the hMNS. Rather, the hMNS seems to respond when an observed movement is matched
      to a motor representation triggered by the intentional goal of the observer.

PMID- 18339410
TI  - Rats exposed to traumatic stress bury unfamiliar objects--a novel measure of
      hyper-vigilance in PTSD models?
AB  - Electric shocks lead to lasting behavioral deficits in rodents, and as such are
      often used to model post-traumatic stress disorder (PTSD) in the laboratory. Here
      we show that a single exposure of rats to 3 mA-strong shocks results in a marked
      social avoidance that lasts at least 28 days; moreover, the response intensifies
      over time. In an attempt to study the impact of cue reminders on the behavior of
      shocked rats, we administered shocks in the presence of a highly conspicuous, 10
      cm-large object. This object was introduced into the home cage of rats 28 days
      after shock exposure. Shocked rats manipulated the object considerably less than
      controls. More importantly, however, the object was buried by shocked rats. This
      behavior was virtually absent in controls. The response strongly depended on the
      intensity of shocks, and was robust. Rats shocked with 3 mA currents spent 40% of
      time burying the object, which was often hardly visible at the end of the 5 min
      test. Subsequent experiments demonstrated that the response was not cue-specific
      as unfamiliar objects were also buried. Rats are well known to bury dangerous
      objects; the shock-prod burying test of anxiety is based on this response.
      Behavioral similarities with this test and the differences from the marble
      burying behavior of mice suggest that traumatized rats bury unfamiliar objects in
      defense, and the response can be interpreted as a sign of hyper-vigilance. We
      further suggest that object burying can be used as a sign of hyper-vigilance in
      models of PTSD.

PMID- 18339411
TI  - High levels of misconceptions and stigma in a community highly endemic for
      podoconiosis in southern Ethiopia.
AB  - The impact of public health interventions for tropical diseases is limited by
      lack of understanding of the sociocultural context into which these interventions
      are delivered. Podoconiosis (endemic non-filarial elephantiasis) is a
      considerable public health problem in Ethiopia, yet little is known about
      community understanding of it. This study aimed to assess the knowledge,
      attitudes and practices of community members towards podoconiosis in a highly
      endemic area in southern Ethiopia. A cross-sectional study was conducted in
      January 2007 among 438 study participants selected by multistage probability
      sampling. Most respondents (93.5%) had seen a patient with podoconiosis and 91.6%
      had heard of the local terms for podoconiosis. The proportion of respondents
      holding at least one misconception about causation was 93.4% (95% CI 91.1-95.7%).
      More than one-half (55.8%) showed stigmatising attitudes towards social
      interactions with podoconiosis patients and 63.8% had unfavourable attitudes
      towards the condition. Just over one-half (55.2%) of respondents were wearing
      shoes during the interview, but shoe wearing was inconsistent and inadequate to
      prevent podoconiosis. In this highly endemic area, the community held significant
      misconceptions about causation, care, treatment and prevention of podoconiosis.
      Community interventions for podoconiosis must include education components aimed
      at dispelling misconceptions and stigma.

PMID- 18339412
TI  - The Ebbinghaus retention curve: training does not increase the ability to apply
      pressure immobilisation in simulated snake bite--implications for snake bite
      first aid in the developing world.
AB  - Pressure immobilisation (PIM) has been recommended for field management of bites
      by some venomous snakes. A narrow range of pressures under the encompassing wrap
      is necessary for PIM to limit venom spread. This study sought to evaluate the
      effect of focused training on volunteers' ability to apply PIM and to retain such
      skill over time. Forty volunteers were randomly divided into two groups: Group 1
      (N=20; controls) received standard written instructions in PIM application; and
      Group 2 (N=20) received focused instruction during a 4-h training session
      (including hands-on practice and real-time feedback regarding pressures
      achieved). After voicing confidence with the technique, volunteers were tested at
      1h, 1 day, 3 days and 3 months post training. One-hour post training, no
      volunteers in the control group were successful in applying PIM with the correct
      pressure. Twelve volunteers (60%) in Group 2 achieved target pressures 1h after
      training. However, there was rapid loss of ability to apply PIM correctly by
      Group 2, falling to just 25% success at 3 days, with little further deterioration
      at 3 months. Neither written instructions nor intense training with feedback
      adequately prepares individuals to apply PIM with correct pressures under the
      wrap.

PMID- 18339413
TI  - Variation in the ovine cortisol response to systemic bacterial endotoxin
      challenge is predominantly determined by signalling within the hypothalamic
      pituitary-adrenal axis.
AB  - Bi-directional communication between the neuroendocrine and immune systems is
      designed, in part, to maintain or restore homeostasis during physiological
      stress. Exposure to endotoxin during Gram-negative bacterial infection for
      example, elicits the release of pro-inflammatory cytokines that activate the
      hypothalamic-pituitary-adrenal axis (HPAA). The secretion of adrenal
      glucocorticoids subsequently down regulates the host inflammatory response,
      minimizing potential tissue damage. Sequence and epigenetic variants in genes
      involved in regulating the neuroendocrine and immune systems are likely to
      contribute to individual differences in the HPAA response, and this may influence
      the host anti-inflammatory response to toxin exposure and susceptibility to
      inflammatory disease. In this study, high (HCR) and low (LCR) cortisol responders
      were selected from a normal population of 110 female sheep challenged iv with
      Escherichia coli endotoxin (400 ng/kg) to identify potential determinants that
      contribute to variation in the cortisol response phenotype. This phenotype was
      stable over several years in the HCR and LCR animals, and did not appear to be
      attributed to differences in expression of hepatic immune-related genes or
      systemic pro-inflammatory cytokine concentrations. Mechanistic studies using
      corticotrophin-releasing factor (0.5 microg/kg body weight), arginine vasopressin
      (0.5 microg/kg), and adrenocorticotropic hormone (0.5 microg/kg) administered iv
      demonstrated that variation in this phenotype is largely determined by signalling
      within the HPAA. Future studies will use this ovine HCR/LCR model to investigate
      potential genetic and epigenetic variants that may contribute to variation in
      cortisol responsiveness to bacterial endotoxin.

PMID- 18339414
TI  - Oxidative stress induced by destruxin from Metarhizium anisopliae (Metch.)
      involves changes in glutathione and ascorbate metabolism and instigates
      ultrastructural changes in the salivary glands of Spodoptera litura (Fab.)
      larvae.
AB  - The cyclodepsipeptidic mycotoxin, destruxin, produced by Metarhizium anisopliae
      is known for its larvicidal properties. The crude destruxin-treated Spodoptera
      litura larvae revealed a decrease in thiol content and an increment in oxidation
      of glutathione to glutathione disulfide and ascorbate to dehydro ascorbate in a
      dose- and time-dependent manner. An increase in the levels of protein carbonyls
      and the free radicals, hydrogen peroxide and hydroxyl radical was also observed.
      These provide a clear indication of oxidative stress. Upon ingestion, destruxin
      causes serious damage to the epithelial cells of the midgut. We report the
      ultrastructural effects of crude destruxin on the salivary glands of 9-day-old S.
      litura larva after 24 h of treatment with the mycotoxin at a dosage of 0.147
      microg/g body wt. (LD(50)). The transmission electron microscopic observations
      revealed characteristic changes in the salivary glands of S. litura which include
      detachment and damage of the microvilli, epithelial cell vacuolization, bleeding
      of the epithelial cells into the salivary gland lumen and disruption of the
      epithelial cell membrane. This investigation focuses salivary glands also as the
      target organ of destruxin apart from the already known midgut, Malphigian tubules
      and haemocytes.

PMID- 18339415
TI  - Toxic response indicators of microcystin-LR in F344 rats following a single-dose
      treatment.
AB  - Microcystin-LR (MCLR) is the most common hepatotoxic cyanotoxin produced
      primarily by Microcystis aeruginosa. In this study, young F344 rats were
      intraperitoneally injected with a single dose (25, 50, 100, and 150 microg/kg) of
      MCLR to explore possible toxic effect and toxic response indicators. Acute toxic
      symptoms, including body weight loss and death, were monitored for 7 days.
      Mortality reached 100% (9/9) in rats treated with a single MCLR dose of 150
      microg/kg. Histopathological examination showed spot necrosis in the liver of
      animals treated at low doses, while massive hemorrhage and widespread necrotic
      foci occurred at higher doses, indicating extensive liver damage. Protein
      phosphatase 2A (PP2A) expression showed a dose-dependent decrease in the liver.
      Immunohistochemical localization indicated that nuclear PP2A was affected first,
      followed by cytoplasmic PP2A. In addition, there was a significant increase in
      sphingolipid levels at higher doses, indicating the involvement of a ceramide
      mediated apoptotic pathway. Expression of apoptosis and cell cycle regulatory
      proteins like Bax, Bcl2, and Bad showed a dose-dependent decrease. This study
      demonstrated that treatment with a single dose of MCLR caused liver damage,
      increased sphingolipid levels, and decreased PP2A expression, which ultimately
      down-regulated the expression of Bcl2 family proteins.

PMID- 18339416
TI  - Mutations in the NS2B and NS3 genes affect mouse neuroinvasiveness of a Western
      European field strain of tick-borne encephalitis virus.
AB  - An attenuated strain (263) of the tick-borne encephalitis virus, isolated from
      field ticks, was either serially subcultured, 5 times in mice, or at 40 degrees C
      in PS cells, producing 2 independent strains, 263-m5 and 263-TR with identical
      genomes; both strains exhibited increased plaque size, neuroinvasiveness and
      temperature-resistance. Sequencing revealed two unique amino acid substitutions,
      one mapping close to the catalytic site of the viral protease. These observations
      imply that virus adaptation from ticks to mammals occurs by selection of pre
      existing virulent variants from the quasispecies population rather than by the
      emergence of new random mutations. The significance of these observations is
      discussed.

PMID- 18339417
TI  - Infectious genomic RNA of Rhopalosiphum padi virus transcribed in vitro from a
      full-length cDNA clone.
AB  - Availability of a cloned genome from which infectious RNA can be transcribed is
      essential for investigating RNA virus molecular mechanisms. To date, no such
      clones have been reported for the Dicistroviridae, an emerging family of
      invertebrate viruses. Previously we demonstrated baculovirus-driven expression of
      a cloned Rhopalosiphum padi virus (RhPV; Dicistroviridae) genome that was
      infectious to aphids, and we identified a cell line (GWSS-Z10) from the glassy
      winged sharpshooter, that supports RhPV replication. Here we report that RNA
      transcribed from a full-length cDNA clone is infectious. Transfection of GWSS-Z10
      cells with the RhPV transcript resulted in cytopathic effects, ultrastructural
      changes, and accumulation of progeny virions, consistent with virus infection.
      Virions from transcript-infected cells were infectious in aphids. This infectious
      transcript of a cloned RhPV genome provides a valuable tool, and a more tractable
      system without interference from baculovirus infection, for investigating
      replication and pathogenesis of dicistroviruses.

PMID- 18339418
TI  - Nitrogen transformation in a denitrification layer irrigated with dairy factory
      effluent.
AB  - Adoption of land-based effluent treatment systems can be constrained by the costs
      and availability of land. Sufficient land area is needed to ensure nitrate
      leaching from applied effluent is minimised. One approach to decrease required
      land area is to enhance N removal by denitrification. Layers of organic matter
      (100 mm thick) were installed below topsoil of a site irrigated with dairy
      factory effluent. These "denitrification" layers were tested to determine whether
      they could decrease nitrate leaching by increasing denitrification. Four plots
      (10x10 m2 each) were constructed with a denitrification layer installed at 300 mm
      below the surface, and N losses were measured in leachate using suction cups
      every 3 weeks for 19 months. N in leachate was compared with 4 control plots.
      Denitrifying enzyme activity, nitrate concentrations, and carbon availability
      were measured in samples collected from the denitrification layers. These
      measurements demonstrated that denitrification occurred in the layer; however,
      denitrification rates were not sufficiently high to significantly decrease
      nitrate leaching. Total N leaching was 296 kg N ha(-1) from control plots and 238
      kg N ha(-1) from plots with denitrification layers; a total of 798 kg N ha(-1)
      was applied in effluent. More than 50% of the leached N to 40 cm was as organic
      N, presumably due to bypass flow. Other studies have demonstrated that thicker
      denitrification layers (more than 300 mm) can reduce nitrate leaching from small
      scale septic tank drainage fields but this study suggests that it is probably not
      practical to use denitrification layers at larger scales.

PMID- 18339419
TI  - Serous papillary adenocarcinoma of the female genital organs and invasive
      micropapillary carcinoma of the breast. Are WT1, CA125, and GCDFP-15 useful in
      differential diagnosis?
AB  - Serous papillary adenocarcinoma of the female genital organs and invasive
      micropapillary carcinoma of the breast have close histologic similarities. Thus,
      when these cancers occur synchronously or metachronously in the same patient, it
      is difficult to determine the primary site. We examined 23 serous papillary
      adenocarcinomas (16 ovarian, 5 endometrial, and 2 peritoneal) and 37 invasive
      micropapillary carcinomas of the breast (12 pure and 25 mixed types) on
      immunohistochemical expression of Wilm's tumor antigen-1 (WT1), CA125, and gross
      cystic disease fluid protein-15 (GCDFP-15), which have been reported to be useful
      in the differential diagnosis of primary ovarian carcinomas versus metastatic
      breast cancer to the ovary. The positive rates of WT1, CA125, and GCDFP-15 in
      serous papillary adenocarcinomas were 78%, 78%, and 0%, respectively, and the
      corresponding rates in invasive micropapillary carcinomas were 3%, 40%, and 38%.
      The CA125-positive rate of invasive micropapillary carcinoma was higher than the
      rate reported for other types of breast carcinomas. We consider CA125 to be not
      always useful in the differential diagnosis of serous papillary adenocarcinoma
      and invasive micropapillary carcinoma. Although the positive rate of WT1 was
      significantly higher in serous papillary adenocarcinoma than in invasive
      micropapillary carcinoma, WT1 expression in endometrial serous papillary
      adenocarcinoma was infrequent (20%). WT1 and GCDFP-15 could be useful markers for
      the differential diagnosis of ovarian and peritoneal serous papillary
      adenocarcinoma versus breast invasive micropapillary adenocarcinoma. However, the
      availability of GCDFP-15 is limited because of the low positive rate of GCDFP-15
      in invasive micropapillary carcinomas.

PMID- 18339420
TI  - A prospective, randomized, double-blinded placebo-controlled comparison of
      extended release oxybutynin versus phenazopyridine for the management of
      postoperative ureteral stent discomfort.
AB  - OBJECTIVES: Ureteral stents commonly cause lower urinary tract and flank
      discomfort. We evaluated the use of extended release oxybutynin versus
      phenazopyridine versus placebo for the management of ureteral stent discomfort
      after ureteroscopy. METHODS: Each of 60 patients who received a unilateral stent
      after ureteroscopy was given a blister pack containing 21 unmarked capsules of
      either extended release oxybutynin 10 mg, phenazopyridine 200 mg, or placebo in a
      prospective, randomized, and double-blinded fashion. Patients were instructed to
      take 1 capsule 3 times daily immediately after the procedure. Patients were given
      50 tablets of oral narcotic to be taken as needed. Patients reported bothersome
      scores for flank pain, suprapubic pain, urinary frequency, urgency, dysuria, and
      hematuria on postoperative day 1, day 2, and the day of stent removal. Narcotic
      use was also recorded. RESULTS: Eight patients were excluded from the analysis
      for stent migration necessitating early removal (1), uncontrollable pain (1),
      failure to complete blister pack (4), and inability to contact for follow-up
      surveys (2). There was no difference in bothersome score among the groups for
      flank pain, suprapubic pain, urinary frequency, urgency, and dysuria. The
      phenazopyridine group reported less hematuria on postoperative day 1 when
      compared with placebo, which was statistically significant. The oxybutynin group
      required fewer narcotics, but this finding was not statistically significant.
      CONCLUSIONS: Although this study failed to show a significant difference in
      bothersome scores among the groups, the small sample size precludes definitive
      conclusion. Future studies pooling these data will determine the overall
      treatment effect and the optimal management of ureteral stent morbidity.

PMID- 18339421
TI  - Maternal insulin-like growth factor-II promotes placental functional development
      via the type 2 IGF receptor in the guinea pig.
AB  - In guinea pigs, maternal insulin-like growth factor (IGF) infusion in early
      pregnancy enhances placental transport near-term, increasing fetal growth and
      survival. The effects of IGF-II, but not IGF-I, appear due to enhanced placental
      labyrinthine (exchange) development. To determine if the type-2 IGF receptor
      (IGF2R) mediates these distinct actions of exogenous IGF-II in the mother, we
      compared the impact of IGF-II with an IGF-II analogue, Leu(27)-IGF-II, which only
      binds the IGF2R. IGF-II, Leu(27)-IGF-II (1mg/kg per day.sc) or vehicle were
      infused from days 20-38 of pregnancy (term = 67 days) and placental structure and
      uptake and transfer of [(3)H]-methyl-D-glucose (MG) and [(14)C]-amino-isobutyric
      acid (AIB) and fetal growth and plasma metabolites, were measured on day 62. Both
      IGF-II and Leu(27)-IGF-II increased the volume of placental labyrinth,
      trophoblast and maternal blood space within the labyrinth and total surface area
      of trophoblast for exchange, compared to vehicle. Leu(27)-IGF-II also reduced the
      barrier to diffusion (trophoblast thickness) compared to vehicle and IGF-II. Both
      IGF-II and Leu(27)-IGF-II increased fetal plasma amino acid concentrations and
      placental transfer of MG to the fetus compared to vehicle, with Leu(27)-IGF-II
      also increasing AIB transport compared with vehicle and IGF-II. In addition,
      Leu(27)-IGF-II increased fetal weight compared to vehicle. In conclusion,
      maternal treatment with IGF-II or Leu(27)-IGF-II in early gestation, induce
      similar placental and fetal outcomes near term. This suggests that maternal IGF
      II in early gestation acts in part via the IGF2R to persistently enhance
      placental functional development and nutrient delivery and promote fetal growth.

PMID- 18339422
TI  - Ornithine decarboxylase attenuates leukemic chemotherapy drugs-induced cell
      apoptosis and arrest in human promyelocytic HL-60 cells.
AB  - Ornithine decarboxylase (ODC), the rate-limiting enzyme of the polyamine
      biosynthetic pathway, plays an important role in cell cycle, tumor promotion and
      anti-apoptosis. In our previous studies, overexpression of ODC prevented
      apoptosis induced by tumor necrosis factor-alpha and methotrexate. We further
      investigated the apoptotic mechanisms of the cancer chemotherapeutic drugs,
      including etoposide (VP-16), paclitaxel (TAX) and cisplatin (CDDP), and the
      influences of ODC on apoptosis and cell cycle. Our results showed that the
      investigated drugs induced caspase-dependent apoptosis, the generation of
      reactive oxygen species (ROS) and the disruption of mitochondrial membrane
      potential (Deltapsi m) in HL-60 cells, all of which were reversed by putrescine,
      glutathione or N-acetyl-l-cysteine. Overexpression of ODC prevented the cancer
      chemotherapeutic drugs-induced apoptosis, ROS generation and the disruption of
      Deltapsi m. After drug administrations, the decline of Bcl-2, cytochrome c
      release and caspases' activation were inhibited by ODC overexpression. In cell
      cycle, ODC overexpressed cells seemed to overcome the G1 arrest and G2/M arrest,
      caused by VP-16 and TAX, respectively, and kept on the cell cycle rolling.
      Overexpression of ODC increased the expression of Cyclin A, D, E and Cdk4 and the
      enzyme activity of Cdk1 and Cdk2 after the treatment of VP-16 and TAX,
      respectively. In conclusions, the cancer chemotherapeutic drugs-induced apoptosis
      is through ROS-related, mitochondria-mediated and caspase-dependent pathways.
      With higher ODC activity, cells are resistant to the cancer chemotherapeutic
      drugs-induced apoptosis and keep on the cell cycle rolling with the significant
      interference in G1/S arrest caused by VP-16 and G2/M arrest by TAX.

PMID- 18339424
TI  - Erythropoietin, the first century.

PMID- 18339423
TI  - Altered gene expression in busulfan-resistant human myeloid leukemia.
AB  - Busulfan (Bu) resistance is a major obstacle to hematopoietic stem cell
      transplantation (HSCT) of patients with chronic or acute myelogenous leukemia
      (CML or AML). We used gene expression analysis to identify cellular factors
      underlying Bu resistance. Two Bu-resistant leukemia cell lines were established,
      characterized and analyzed for differentially expressed genes. The CML
      B5/Bu250(6) cells are 4.5-fold more resistant to Bu than their parental B5 cells.
      The AML KBM3/Bu250(6) cells are 4.0-fold more Bu-resistant than KBM3 parental
      cells. Both resistant sublines evade Bu-mediated G2-arrest and apoptosis with
      altered regulations of CHK2 and CDC2 proteins, constitutively up-regulated anti
      apoptotic genes (BCL-X(L), BCL2, BCL2L10, BAG3 and IAP2/BIRC3) and down-regulated
      pro-apoptotic genes (BIK, BNIP3, and LTBR). Bu-induced apoptosis is partly
      mediated by activation of caspases; use of the inhibitor Z-VAD-FMK completely
      abrogated PARP1 cleavage and reduced apoptosis by approximately 50%. Furthermore,
      Bu resistance in these cells may be attributed in part to up-regulation of HSP90
      protein and activation of STAT3. The inhibition of HSP90 with geldanamycin
      attenuated phosphorylated STAT3 and made B5/Bu250(6) and KBM3/Bu250(6) more Bu
      sensitive. The analysis of cells derived from patients classified as either
      clinically resistant or sensitive to high-dose Bu-based chemotherapy indicated
      alterations in gene expression that were analogous to those observed in the in
      vitro model cell lines, confirming the potential clinical relevance of this model
      for Bu resistance.

PMID- 18339425
TI  - Oxidative stress, evident in antioxidant defences and damage products, in rainbow
      trout caged outside a sewage treatment plant.
AB  - Sewage treatment plants (STPs) are common sources of a wide variety of chemicals
      entering into the aquatic environment. We have investigated the effects of STP
      effluent on oxidative stress parameters in rainbow trout via measurements of
      several enzymatic antioxidants as well as the molecular antioxidant glutathione
      (GSH). In addition, we have measured levels of oxidative damage, i.e. protein
      carbonyls and lipid peroxides. Our findings indicate that STP effluent does
      contain prooxidants that affect fish. Oxidative damage was a more consistent
      indicator of exposure to prooxidants than antioxidant enzymes. Protein carbonyls
      and lipid peroxides were both elevated (1.3- and 1.8-fold increases,
      respectively) in fish caged at the STP site compared with reference site as was
      the amount of oxidized GSH (GSSG), which showed a 3-fold increase. Antioxidant
      enzymes showed no clear-cut response. Additionally, older pollutants that have
      been present in down stream sediment for decades had no effects on the parameters
      measured here.

PMID- 18339426
TI  - TLR4/CD14-mediated PI3K activation is an essential component of interferon
      dependent VSV resistance in macrophages.
AB  - Phosphatidylinositol-3-phosphate kinase (PI3K) has been reported to exhibit anti
      inflammatory roles as a negative modulator of the NF-kappaB pathway (MyD88- and
      Mal-dependent) triggered upon Toll-like receptor (TLR)4 activation by
      lipopolysaccharide (LPS). Here, we investigated the role of PI3K on the TLR4
      dependent, MyD88-independent signaling cascade which is activated in macrophages
      infected by Vesicular Stomatitis Virus (VSV) and leads to interferon production,
      thus conferring antiviral protection. We show that VSV induces TLR4 (and CD14)
      dependent Akt phosphorylation. We observed hypersusceptibility to viral
      infections after pharmacological inactivation of the PI3K pathway in macrophages,
      which indicates that normal PI3K functions are critical for type I interferon
      synthesis and viral resistance. Conversely, we noticed increased resistance in
      macrophages isolated from genetically modified mice in which the PI3K pathway is
      constitutively active. Our data, which demonstrate that PI3K-Akt axis is an
      important component of the TLR4-dependent antiviral mechanism, also indicate that
      pharmacological modulation of this pathway to regulate the inflammatory response
      could promote viral susceptibility.

PMID- 18339427
TI  - Human F(ab')2-containing immune complexes together with anti-hinge natural
      antibodies stimulate complement amplification in vitro and in vivo.
AB  - The systemic inflammatory response syndrome (SIRS) is triggered by C5a generation
      following an excessive complement amplification, but it has remained unclear how
      complement amplification is stimulated. It is known that neutrophilic elastase
      can cleave IgG to F(ab')(2) and that F(ab')(2)-containing immune complexes
      (F(ab')(2)-IC) stimulate complement amplification together with an unidentified
      plasma factor. We show that absorption of plasma on F(ab')(2) from human IgG
      removed this factor and prevented F(ab')(2)-IC from stimulating complement
      amplification. The required factor was purified from pooled whole human IgG
      (IVIG) as those naturally occurring antibodies (NAbs) that bind to F(ab')(2), but
      not to intact IgG. These "anti-hinge NAbs" restored complement amplification by
      F(ab')(2)-IC in absorbed plasma. Anti-hinge NAbs must have formed secondary,
      rigidified IC from F(ab')(2)-IC, because the F(ab')(2) fragments evidently
      captured dimeric C3b, known as a potent C3 convertase precursor. This process may
      also stimulate complement amplification in vivo, because plasma from septic
      patients at the onset of SIRS indeed contained F(ab')(2) fragments. The
      concentrations of F(ab')(2) and that of factor Bb, an unbiased measure of
      complement amplification, correlated linearly with that of released elastase.
      Moreover, the F(ab')(2) fragments migrated on gelfiltration columns together with
      anti-hinge NAbs as ICs with MW of up to approximately 750kDa, as verified on
      plasma of each of the nine patients studied. These findings provide for the first
      time a plausible mechanism of how F(ab')(2)-containing immune complexes stimulate
      complement amplification together with anti-hinge NAbs. The same mechanism may
      contribute to complement overreaction at the onset of SIRS.

PMID- 18339428
TI  - A novel stimulus artifact removal technique for high-rate electrical stimulation.
AB  - Electrical stimulus artifact corrupting electrophysiological recordings often
      makes the subsequent analysis of the underlying neural response difficult. This
      is particularly evident when investigating short-latency neural activity in
      response to high-rate electrical stimulation. We developed and evaluated an off
      line technique for the removal of stimulus artifact from electrophysiological
      recordings. Pulsatile electrical stimulation was presented at rates of up to 5000
      pulses/s during extracellular recordings of guinea pig auditory nerve fibers.
      Stimulus artifact was removed by replacing the sample points at each stimulus
      artifact event with values interpolated along a straight line, computed from
      neighbouring sample points. This technique required only that artifact events be
      identifiable and that the artifact duration remained less than both the inter
      stimulus interval and the time course of the action potential. We have
      demonstrated that this computationally efficient sample-and-interpolate technique
      removes the stimulus artifact with minimal distortion of the action potential
      waveform. We suggest that this technique may have potential applications in a
      range of electrophysiological recording systems.

PMID- 18339429
TI  - Antioxidant enzyme and malondialdehyde levels in patients with social phobia.
AB  - A growing body of reports have indicated that free radicals are involved in the
      etiopathogenesis of some neuropsychiatric disorders. In the present study, we
      aimed to evaluate whether antioxidant enzymes (superoxide dismutase; SOD,
      glutathione peroxidase; GSH-Px, and catalase; CAT) activity levels and
      malondialdehyde (MDA), a product of lipid peroxidation, were associated with
      social phobia (SP). Eighteen patients diagnosed with SP and 18 healthy controls
      were enrolled. A clinical evaluation and measurements of MDA, SOD, GSH-Px and CAT
      were performed. Additionally, all patients were assessed with the Liebowitz
      Social Anxiety Scale (LSAC). The mean MDA, SOD, GSH-Px and CAT levels in the
      patient group were significantly higher than those in the control group. There
      was a positive correlation between LSAC scores and MDA, SOD, GSH-Px and LSAC
      levels, and between the duration of illness, and MDA, SOD and CAT levels in the
      patient group. In conclusion, our results suggest that there may be a
      relationship between increased antioxidant enzyme levels and MDA, and SP.

PMID- 18339430
TI  - Requirement of caspases and p38 MAPK for TRAIL-mediated ICAM-1 expression by
      human astroglial cells.
AB  - Among tumor necrosis factor (TNF) superfamily, TNF-related apoptosis inducing
      ligand (TRAIL) along with TNF-alpha and FasL is known as death ligand due to its
      selective cytotoxicity against transformed tumor cells. TRAIL can also induce
      alternative angiogenic and/or proinflammatory signals other than apoptosis,
      however, the molecular mechanisms responsible for the alternative signals have
      not been detailed yet. Intercellular adhesion molecule-1 (ICAM-1) is thought to
      be involved in the processes of metastasis and angiogenesis in various tumors. We
      investigated the molecular mechanisms responsible for ICAM-1 expression by death
      ligands in human astroglial cells to delineate the alternative signals of these
      ligands. Here, we demonstrate that (1) death ligands induced expression of ICAM-1
      at the mRNA and protein levels in human astroglial cells; (2) pre-treatment of z
      VAD-fmk and/or SB202190 suppressed death ligand-induced ICAM-1 expression and
      subsequent adhesion of activated monocytic cells; and (3) inhibition of caspase
      suppressed death ligand-induced phosphorylation of p38 MAPK and IKK. These
      findings suggest biological function of death receptors other than apoptosis in
      human astroglial cells, and the involvement of caspase and/or p38 MAPK in
      alternative signaling through death receptors.

PMID- 18339432
TI  - Treatment of bilateral choanal atresia in the premature infant.
AB  - An innovative technique for choanal atresia repair was used for a unique case of
      bilateral choanal atresia in a 28-week premature newborn. Endoscopic transnasal
      KTP laser was employed as an alternative to standard instrumentation to reach the
      very small atretic plate of a premature nose, providing good visualization of the
      operative field, thereby avoiding damage to the adjacent structures. The
      successful repair allowed for early extubation and avoidance of a tracheotomy.
      The clinical and surgical aspects of the case are discussed. With the likelihood
      of encountering more premature infants with choanal atresia given the improving
      neonatal intensive care, we propose that KTP laser repair be considered as an
      alternative to conventional procedures for this particular population.

PMID- 18339431
TI  - A novel DNA vaccine for protective immunity against virulent Mycobacterium bovis
      in mice.
AB  - Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB). The
      proteins Ag85B, MPB64, and ESAT-6 are the major immunogenic antigens of M. bovis;
      these proteins play important roles in inducing immune responses that confer
      resistance against infections. In the present study, we used pcDNA3.1(+) as a
      vector and constructed various DNA vaccines with the genes encoding the three
      antigens mentioned above. This procedure involved the following steps: fusion of
      two genes (pcDNA-MPB64-Ag85B, pcMA), fusion of three genes (pcDNA-MPB64-Ag85B
      ESAT-6, pcMAE), bivalent combinations (pcDNA-Ag85B+pcDNA-MPB64, pcA+M), and
      trivalent combinations (pcDNA-Ag85B+pcDNA-MPB64+pcDNA-ESAT-6, pcA+M+E). The
      immune response to the DNA vaccines was evaluated based on serum antibody titers,
      lymphocyte proliferation assay, and titers of the cytokines interferon-gamma (IFN
      gamma) and interleukin-2 (IL-2). The protective efficacy following challenge with
      a virulent M. bovis strain, C68001, was evaluated based on survival rate,
      bacterial loads in lung tissue, and histopathologic changes. A significant 2-fold
      increase in serum antibody levels was observed in mice vaccinated with fusion DNA
      (two or three genes). Furthermore, the lymphocyte proliferation (SI) values and
      the levels of IFN-gamma and IL-2 were higher in mice vaccinated with fusion DNA
      (two or three genes) than in those immunized with polyvalent combination DNA
      vaccines (P<0.05). Additionally, the fusion DNA vaccines provided protection that
      was superior to that provided by the polyvalent combination DNA vaccines
      following challenge with M. bovis strain C68001. The protective efficacy of the
      fusion DNA vaccines in mice immunized three times was equivalent to the
      protective efficacy in mice immunized once with the Bacillus Calmette-Guerin
      (BCG) vaccine. This suggests that fusion DNA vaccine represent a promising
      approach for the prevention of bTB.

PMID- 18339433
TI  - A sensitive and quantitative assay for normal PrP in plasma.
AB  - Transmissible spongiform encephalopathies can be transmitted by blood
      transfusion. The risk of spreading the disease among the human population could
      be mitigated with the implementation of a blood screening assay. We developed a
      two-antibody assay for PrP detection in plasma using the ORIGEN technology with a
      protocol modification to improve the limit of detection and to increase the
      sample volume assayed. In the standard 200 microL format, the assay had a
      detection limit of 7-10 pg of recombinant PrP and 3 pg in 1 mL final volume
      implementation. PrP concentration measured in normal and scrapie-infected hamster
      brains was 7.5+/-0.9 and 57.3+/-9.6 microg/g, respectively. After a concentration
      step with an immuno-affinity resin, plasma PrP(c) was detected by Western blot
      and its concentration was measured at 3.5+/-0.8 ng/mL. From these data and
      assuming that blood has the same specific infectivity as brain, we estimated the
      concentration of abnormal PrP in hamster-infected plasma to be 32 f g/mL. The
      assay also detected abnormal brain PrP spiked into plasma although the limit of
      detection was affected. This is a novel and sensitive assay for the detection of
      PrP in plasma that could be developed into a platform for a plasma-based TSE
      test.

PMID- 18339434
TI  - Role of dopamine D1 and D2 receptors in the nucleus accumbens shell on the
      acquisition and expression of fructose-conditioned flavor-flavor preferences in
      rats.
AB  - Systemic administration of dopamine D1 (SCH23390) and less so D2 (raclopride)
      receptor antagonists significantly reduce acquisition and expression of fructose
      conditioned flavor preferences (CFP). Because dopamine in the nucleus accumbens
      shell (NAcS) is implicated in food reward, the present study examined whether
      NAcS D1 or D2 antagonists altered acquisition and/or expression of fructose-CFP.
      In Experiment 1, food-restricted rats with bilateral NAcS cannulae were trained
      to drink a fructose (8%)+saccharin (0.2%) solution mixed with one flavor (CS+/Fs)
      and a less-preferred 0.2% saccharin solution with mixed another flavor (CS-/s).
      Unlimited two-bottle tests with the two flavors in saccharin (0.2%: CS+/s, CS-/s)
      occurred 10 min following total bilateral NAcS doses of 0, 12, 24 or 48 nmol of
      SCH23390 or raclopride. Preference for CS+/s over CS-/s following vehicle
      treatment (76%) was significantly reduced by SCH23390 (48 nmol, 62%) and
      raclopride (24 nmol, 63%). In Experiment 2, rats received bilateral NAcS
      injections (12 nmol) of SCH23390 or raclopride on one-bottle training (16 ml)
      days. Yoked control rats received vehicle and were limited to the CS intakes of
      the D1 and D2 groups, whereas untreated controls without injections received
      their CS ration during training. Subsequent unlimited two-bottle tests revealed
      initial preferences of CS+/s over CS-/s in all groups that remained stable in
      untreated and yoked controls, but were lost over the six tests sessions in D1 and
      D2 groups. These data indicate that NAcS D1 and D2 antagonists significantly
      attenuated the expression of the fructose-CFP and did not block acquisition, but
      hastened extinction of fructose-CFP.

PMID- 18339435
TI  - Selection of reliable reference genes for qRT-PCR studies on cetacean fibroblast
      cultures exposed to OCs, PBDEs, and 17beta-estradiol.
AB  - Quantitative real-time PCR (qRT-PCR) represents an effective molecular technique
      for the detection of mRNA expression in biological samples. Its sensitivity
      allows the quantification of slight changes in the regulation of gene
      transcription but is strictly dependent upon the method followed during the
      normalization procedure. Relative quantification determines changes in the steady
      state mRNA levels of genes across multiple samples and it is assessed by
      comparison with the levels of one or more internal control RNA. In this context,
      the choice of constitutively expressed control genes, whose transcription is not
      affected by the contaminants, appears to be fundamental for the reliability of
      this technique. During this study, fibroblast cell cultures originated from
      integumentum biopsies, sampled in the cetacean species Stenella coeruleoalba,
      have been exposed for 6h to increasing concentrations of different mixtures of
      compounds with endocrine disruptor capacities (EDCs): organochlorines (OCs),
      polybrominated diphenyl ethers (PBDEs), and 17beta-estradiol. Ten common
      housekeeping genes have been tested for the expression of their transcripts in
      exposed cell cultures using qRT-PCR assays and raw data were analyzed with the
      two Excel applets geNorm and NormFinder. The genes encoding for SDHA, GAPDH and
      YWHAZ appear to be the most reliable controls, respectively, for the OC, PBDE and
      17beta-estradiol treatments. These results clearly show that the transcription of
      even widely diffused control genes can be regulated by different treatments and
      underlie the importance of a careful selection of the optimal housekeeping genes
      in toxicological studies.

PMID- 18339436
TI  - Hepatic gene expression profiling using GeneChips in zebrafish exposed to 17alpha
      methyldihydrotestosterone.
AB  - Concentration and time-dependent changes in hepatic gene expression were examined
      in adult, female zebrafish (Danio rerio) exposed to 0, 0.1, 0.7, 4.9 microg/L of
      a model androgen, 17alpha-methyldihydrotestosterone (MDHT). At 24 and 168 h, fish
      were sacrificed and liver was extracted for gene expression analysis using custom
      Affymetrix GeneChip Zebrafish Genome Microarrays. In an effort to link gene
      expression changes to higher levels of biological organization, blood was
      collected for measurement of plasma steroid hormones (17beta-estradiol (E2),
      testosterone (T)) and vitellogenin (VTG) using ELISA. Body and ovary weight were
      also measured. A significant reduction in E2 occurred at 24h (0.7 and 4.9
      microg/L) and 168 h (4.9 microg/L) following MDHT exposure. In contrast, T was
      significantly increased at 24h (4.9 microg/L) and 168 h (0.1, 0.7, 4.9 microg/L).
      171 and 575 genes were significantly affected in a concentration-dependent manner
      at either 24 or 168 h by MDHT exposure at p<or=0.001 and p<or=0.01, respectively.
      Genes involved in retinoic acid metabolism (e.g. aldehyde dehydrogenase 8, member
      A1; retinol dehydrogenase 12), steroid biosynthesis and metabolism (e.g.
      hydroxysteroid (11beta) dehydrogenase 2; hydroxy-delta-5-steroid dehydrogenase, 3
      beta-), hormone transport (e.g. sex hormone binding globulin), and regulation of
      cell growth and proliferation (e.g. N-myc downstream regulated gene 1;
      spermidinespermine N(1)-acetyltransferase) were affected by MDHT exposure. In
      this study, we identified genes involved in a variety of biological processes
      that have the potential to be used as markers of exposure to androgenic
      substances. Genes identified in this study provide information on the potential
      mode of action of strong androgens in female fish. In addition, when used for
      screening of EDC's, these genes may also serve as sensitive markers of exposure
      to androgenic compounds.

PMID- 18339437
TI  - Predictive items of 2-year mortality in nonagenarians with cognitive impairment
      at baseline: the NonaSantfeliu study.
AB  - We aimed to identify a set of predictors of mortality at 2-year follow-up in a
      cohort of nonagenarians with cognitive impairment at baseline. The following
      variables were evaluated; functional status determined by the indices of Barthel
      Index for basic and Lawton and Brody for instrumental activities of daily living,
      while cognition was assessed using the Spanish version of the mini-mental state
      examination (MEC). Cognitive impairment was graded as severe for those having MEC
      scores of 0-17 and mild for scores of 18-23. A total of 77 nonagenarians with a
      MEC score of 23 or below were included: 61 women (79.25%) and 16 men, with a mean
      age of 93.7 (3.4) years. The rate of mortality was 55.8%. According to MEC scores
      the proportion of deaths during the 2-year follow-up period ranged from 35.2% (6
      out of 17) among mildly impaired participants to 61.6% (37 out of 60) among
      severely impaired participants (p=0.05). Multivariate regression analysis showed
      that the risk of dying in this cohort was associated with being older (p<0.01, OR
      1.23, 95% CI 1.03-1.4) and having a previous history of heart failure (p<0.0001,
      OR 8.72, 95% CI 2.66-28.5). In conclusion age and heart failure predict mortality
      among nonagenarians with prior cognitive impairment.

PMID- 18339438
TI  - Simulating the spread of classical swine fever virus between a hypothetical wild
      boar population and domestic pig herds in Denmark.
AB  - Denmark has no free-range wild-boar population. However, Danish wildlife
      organizations have suggested that wild boar should be reintroduced into the wild
      to broaden national biodiversity. Danish pig farmers fear that this would lead to
      a higher risk of introduction of classical swine fever virus (CSFV), which could
      have enormous consequences in terms of loss of pork exports. We conducted a risk
      assessment to address the additional risk of introducing and spreading CSFV due
      to the reintroduction of wild boar. In this paper, we present the part of the
      risk assessment that deals with the spread of CSFV between the hypothetical wild
      boar population and the domestic population. Furthermore, the economic impact is
      assessed taking the perspective of the Danish national budget and the Danish pig
      industry. We used InterSpreadPlus to model the differential classical swine fever
      (CSF) risk due to wild boar. Nine scenarios were run to elucidate the effect of:
      (a) presence of wild boar (yes/no), (b) locations for the index case (domestic
      pig herd/wild-boar group), (c) type of control strategy for wild boar
      (hunting/vaccination) and (d) presence of free-range domestic pigs. The presence
      of free-range wild boar was simulated in two large forests using data from
      wildlife studies and Danish habitat data. For each scenario, we estimated (1) the
      control costs borne by the veterinary authorities, (2) the control-related costs
      to farmers and (3) the loss of exports associated with an epidemic. Our
      simulations predict that CSFV will be transmitted from the domestic pig
      population to wild boar if the infected domestic pig herd is located close to an
      area with wild boar (<5 km). If an outbreak begins in the wild-boar population,
      the epidemic will last longer and will occasionally lead to several epidemics
      because of periodic transfer of virus from groups of infected wild boar to
      domestic pig herds. The size and duration of the epidemic will be reduced if
      there are no free-range domestic pig herds in the area with CSF-infected wild
      boar. The economic calculations showed that the total national costs for Denmark
      (i.e. the direct costs to the national budget and the costs to the pig industry)
      related to an outbreak of CSF in Denmark will be highly driven by the reactions
      of the export markets and in particular of the non-EU markets. Unfortunately,
      there is a substantial amount of uncertainty surrounding this issue. If hunting
      is used as a control measure, the average expenses related to a CSF outbreak will
      be 40% higher if wild boar are present compared with not present. However, a
      vaccination strategy for wild boar will double the total costs compared with a
      hunting strategy.

PMID- 18339439
TI  - Hepatitis B viruses: reverse transcription a different way.
AB  - Hepatitis B virus (HBV), the causative agent of B-type hepatitis in humans, is
      the type member of the Hepadnaviridae, hepatotropic DNA viruses that replicate
      via reverse transcription. Beyond long-established differences to retroviruses in
      gene expression and overall replication strategy newer work has uncovered
      additional distinctions in the mechanism of reverse transcription per se. These
      include protein-priming by the unique extra terminal protein domain of the
      reverse transcriptase (RT) utilizing an RNA hairpin for de novo initiation of
      first strand DNA synthesis, and the strict dependence of this process on cellular
      chaperones. Recent in vitro reconstitution systems enabled first biochemical
      insights into this multifactorial reaction, complemented by high resolution
      structural information on the RNA, though not yet the protein, level. Genetic
      approaches have revealed long-distance interactions in the nucleic acid templates
      as an important factor enabling the puzzling template switches required to
      produce the relaxed circular (RC) DNA found in infectious virions. Finally, the
      failure of even potent HBV RT inhibitors to eliminate nuclear covalently closed
      circular (ccc) DNA, the functional equivalent of integrated proviral DNA, has
      spurred a renewed interest in the mechanism of cccDNA generation. These new
      developments are in the focus of this review.

PMID- 18339440
TI  - A report on the diagnosis of intermediate hyperglycemia in Korea: A pooled
      analysis of four community-based cohort studies.
AB  - Many studies show poor agreement between fasting plasma glucose (FPG)-based and 2
      h postchallenge glucose (2-h PG)-based criteria to assess glucose metabolism. We
      examined the rate of agreement between FPG- and 2-h PG-based criteria in the
      diagnosis of intermediate hyperglycemia in four representative cohort studies in
      South Korea and compared the clinical characteristics and biochemical parameters
      in subjects with impaired fasting glucose (IFG) according to their FPG values. Of
      6234 subjects from four population-based studies performed from 1993 to 2000,
      4610 individuals with data from a 75g oral glucose tolerance test (OGTT) and no
      previous history of diabetes were selected. We examined the concordance rate
      between the FPG and 2-h PG-based criteria. We also investigated the differences
      in the clinical characteristics and biochemical parameters between individuals
      with IFG according to their FPG values. The fasting and 2-h PG criteria had large
      discordance rates in the diagnosis of diabetes and impaired glucose tolerance
      (IGT) in Korean adults. When individuals with IFG were classified into stage 1
      [5.6-6.1mmol/L (100-109mg/dL)] and stage 2 [6.1-7.0mmol/L (110-125mg/dL)] IFG,
      individuals with stage 2 IFG are more obese and had higher blood pressure and
      total cholesterol and triglycerides concentrations compared with those with stage
      1 IFG. In addition, more individuals with stage 2 IFG were with diabetes as
      determined by a 2-h PG>or=11.1mmol/L (14.1% vs. 1.9%) (P<0.05). Considering the
      poorer metabolic profile and higher percentage of people with diabetes by OGTT,
      these data indicate that, in the Korean population, individuals with stage 2 IFG
      should be treated differently from those with stage 1 IFG. To detect more cases
      of diabetes, the OGTT is recommended for all individuals with stage 2 IFG and
      cases with stage 1 IFG with some additional risk factors for diabetes.

PMID- 18339441
TI  - What glucose target should we aim for in myocardial infarction?
AB  - Hyperglycaemia in the period following myocardial infarction is associated with
      increased mortality and there is some evidence that its treatment can improve
      survival. However, it remains unclear as to what the ideal glucose targets might
      be. This study examined observational data taken from a previously reported
      randomised controlled trial of insulin therapy for myocardial infarction (The
      Hyperglycaemia: Intensive Insulin Infusion In Infarction Study), to determine
      optimal glucose levels for this period. Capillary glucose readings were recorded
      at 8 standard time points for 234 subjects in first 24h after myocardial
      infarction. Survival over 6 months was analysed according to whether 80% of each
      subject's glucose readings were below specified glucose thresholds (Achievers) or
      not (Non-Achievers). We found that the glucose threshold at which there was
      greatest separation in mortality between Achievers and Non-Achievers was at
      8mmol/L [144mg/dL] (6 month mortality 1.6% vs. 9.1%, p=0.05). Therefore subjects
      who maintained the majority of their blood glucose levels below 8mmol/L following
      myocardial infarction had optimal survival outcomes. We suggest that this might
      be an appropriate glucose target to aim for in the peri-infarct period.

PMID- 18339442
TI  - Rapid overgrowth of a fetus after interruption of insulin therapy in a diabetic
      woman.
AB  - We experienced a case of fetal overgrowth probably due to maternal hyperglycemia
      following the interruption of insulin therapy in a woman with gestational
      diabetes mellitus (GDM), probably undiagnosed type 2 diabetes mellitus. A 27-year
      old Japanese woman was referred to our center because of GDM at 15 weeks of
      gestation. During the course of her educational admission, diet control and
      insulin therapy resulted in favorable blood sugar levels and she was discharged
      at 17 weeks of gestation. During these periods, fetal growth remained below
      average at between -1 and -1.5 S.D. After a check-up in the 29th week, she failed
      to appear for any further appointments. After the onset of labor, at 38 weeks of
      gestation, she suddenly consulted her former physician who delivered a baby
      weighing 4852g by cesarean section on the 38th week. A noteworthy point in this
      case is the growth curve of the fetus. Even if rapid overgrowth is assumed,
      starting after the time of interruption of insulin at 30 weeks of gestation,
      fetal weight gain appears to be about 400g per week, suggesting a weight increase
      at twice the normal rate. This case prompted us to keep in mind that rigid
      glycemic control will prevent the development of fetal macrosomia in diabetic
      pregnant women.

PMID- 18339443
TI  - Two translesion synthesis DNA polymerase genes, AtPOLH and AtREV1, are involved
      in development and UV light resistance in Arabidopsis.
AB  - Plants are continually exposed to external and internal DNA-damaging agents.
      Although lesions can be removed by different repair processes, damages often
      remain in the DNA during replication. Synthesis of template damages requires the
      replacement of replicative enzymes by translesion synthesis polymerases, which
      are able to perform DNA synthesis opposite specific lesions. These proteins, in
      contrast to replicative polymerases, operate at low processivity and fidelity.
      DNA polymerase eta and Rev 1 are two proteins found in eukaryotes that are
      involved in translesion DNA synthesis. In Arabidopsis, DNA polymerase eta and Rev
      1 are encoded by AtPOLH and AtREV1 genes, respectively. Transgenic plants over
      expressing AtPOLH showed increased resistance to ultraviolet light. Only plants
      with moderate AtREV1 over-expression were obtained, indicating that this enzyme
      could be toxic at high levels. Transgenic plants that over-expressed or disrupted
      AtREV1 showed reduced germination percentage, but the former exhibited a higher
      stem growth rate than the wild type during development.

PMID- 18339444
TI  - Consensus statement on definitions of disease, end points, and therapeutic
      response for pemphigus.
AB  - Our scientific knowledge of pemphigus has dramatically progressed in recent
      years. However, despite the availability of various therapeutic options for the
      treatment of inflammatory diseases, only a few multicenter controlled trials have
      helped to define effective therapies in pemphigus. A major obstacle in comparing
      therapeutic outcomes between centers is the lack of generally accepted
      definitions and measurements for the clinical evaluation of patients with
      pemphigus. Common terms and end points of pemphigus are needed so that experts in
      the field can accurately measure and assess disease extent, activity, severity,
      and therapeutic response, and thus facilitate and advance clinical trials. This
      consensus statement from the International Pemphigus Committee represents 2 years
      of collaborative efforts to attain mutually acceptable common definitions for
      pemphigus. These should assist in development of consistent reporting of outcomes
      in future studies.

PMID- 18339445
TI  - Daily hassles and emotional eating in obese adolescents under restricted dietary
      conditions--the role of ruminative thinking.
AB  - Emotional eating is conceptualized as eating in response to negative affect or
      distress and is discussed as a mechanism leading to eating binges. Recent
      evidence suggests that eating may not only be triggered by negative affect, but
      also ruminative thinking. We report results of an experience sampling study
      examining the role of rumination for emotional eating in 16 obese adolescents
      (M=15.5 years, S.D.=1.4; range 14-17, body mass index M = 31.1 kgm(-2), S.D.=5.5)
      under restricted dietary conditions. We hypothesized that daily hassles type of
      stress predicted the individuals' desire to eat, with the predictive value
      further increased when negative affect and rumination were accounted for. The
      results of mixed regression modeling were in line with our predictions,
      suggesting a significant contribution of ruminative thinking to the mechanisms of
      negative affect induced eating.

PMID- 18339446
TI  - A comparison of observed versus documented physician assessment and treatment of
      pain: the physician record does not reflect the reality.
AB  - STUDY OBJECTIVE: The Joint Commission requires "appropriate assessment" of
      patients presenting with painful conditions. Compliance is usually assessed
      through retrospective chart analysis. We investigate the discrepancy between
      observed physician pain assessment and that subsequently documented in the
      medical record. METHODS: This was an observational study using a trained
      investigator watching bedside interactions of emergency physicians. Using a
      priori definitions, the investigator recorded whether the patient volunteered the
      presence of pain, physician inquiry about pain, attempts to quantify the pain,
      treatment offered/rendered, and any assessment of the response to therapy. An
      independent investigator subsequently assessed the patient's chart for
      documentation of pain assessment, therapy rendered, and response to treatment.
      Children younger than 5 years and patients with major trauma, altered mental
      status, or nontraumatic chest pain were excluded. The institutional review board
      approved the protocol, the physicians agreed to participate in an "ergonomic
      study" without knowing the exact nature of data collection, and patients released
      their records. RESULTS: The investigator observed 209 patient encounters.
      Physicians acknowledged the patients' pain 98.1% of the time but documented its
      presence in 91.7%. Physicians attempted to quantify the patient's pain in 61.5%
      of encounters but documented that attempt in only 38.9%. Treatment was offered in
      79.9% and recorded in 31.7% of charts. When treatment was offered, the patient's
      response to the therapy was recorded only 28% of the time. CONCLUSION: Physicians
      almost always assess and treat patient pain but infrequently record those
      efforts. The patient's chart is a poor surrogate marker for pain assessment and
      care by emergency physicians and may not be suitable for use as a compliance
      assessment tool. Research methodology using retrospective chart analysis may be
      affected by this phenomenon, suggesting the potential for underestimation of
      patient pain assessment and treatment by emergency physicians.

PMID- 18339447
TI  - A critical comparison of clinical decision instruments for computed tomographic
      scanning in mild closed traumatic brain injury in adolescents and adults.
AB  - STUDY OBJECTIVE: A number of clinical decision aids have been introduced to limit
      unnecessary computed tomographic scans in patients with mild traumatic brain
      injury. These aids differ in the risk factors they use to recommend a scan. We
      compare the instruments according to their sensitivity and specificity and
      recommend ones based on incremental benefit of correctly classifying patients as
      having surgical, nonsurgical, or no intracranial lesions. METHODS: We performed a
      secondary analysis of prospectively collected database from 7,955 patients aged
      10 years or older with mild traumatic brain injury to compare sensitivity and
      specificity of 6 common clinical decision strategies: the Canadian CT Head Rule,
      the Neurotraumatology Committee of the World Federation of Neurosurgical
      Societies, the New Orleans, the National Emergency X-Radiography Utilization
      Study II (NEXUS-II), the National Institute of Clinical Excellence guideline, and
      the Scandinavian Neurotrauma Committee guideline. Excluded from the database were
      patients for whom the history of trauma was unclear, the initial Glasgow Coma
      Scale score was less than 14, the injury was penetrating, vital signs were
      unstable, or who refused diagnostic tests. Patients revisiting the emergency
      department within 7 days were counted only once. RESULTS: The percentage of scans
      that would have been required by applying each of the 6 aids were Canadian CT
      head rule (high risk only) 53%, Canadian (medium & high risk) 56%, the
      Neurotraumatology Committee of the World Federation of Neurosurgical Societies
      56%, New Orleans 69%, NEXUS-II 56%, National Institute of Clinical Excellence
      71%, and the Scandinavian 50%. The 6 decision aids' sensitivities for surgical
      hematomas could not be distinguished statistically (P>.05). Sensitivity was 100%
      (95% confidence interval [CI] 96% to 100%) for NEXUS-II, 98.1% (95% CI 93% to
      100%) for National Institute of Clinical Excellence, and 99.1% (95% CI 94% to
      100%) for the other 4 clinical decision instruments. Sensitivity for any
      intracranial lesion ranged from 95.7% (95% CI 93% to 97%) (Scandinavian) to 100%
      (95% CI 98% to 100%) (National Institute of Clinical Excellence). In contrast,
      specificities varied between 30.9% (95% CI 30% to 32%) (National Institute of
      Clinical Excellence) and 52.9% (95% CI 52% to 54) (Scandinavian). CONCLUSION:
      NEXUS-II and the Scandinavian clinical decision aids displayed the best
      combination of sensitivity and specificity in this patient population. However,
      we cannot demonstrate that the higher sensitivity of NEXUS-II for surgical
      hematomas is statistically significant. Therefore, choosing which of the 2
      clinical decision instruments to use must be based on decisionmakers' attitudes
      toward risk.

PMID- 18339448
TI  - Why does the sensitivity of computed tomographic scan for detecting subarachnoid
      blood never improve?

PMID- 18339449
TI  - A prospective, randomized trial of an emergency department observation unit for
      acute onset atrial fibrillation.
AB  - STUDY OBJECTIVE: An emergency department (ED) observation unit protocol for the
      management of acute onset atrial fibrillation is compared with routine hospital
      admission and management. METHODS: Adult patients presenting to the ED with
      atrial fibrillation of less than 48 hours' duration without hemodynamic
      instability or other comorbid conditions requiring hospitalization were enrolled.
      Participants were randomized to either ED observation unit care or routine
      inpatient care. The ED observation unit protocol included pulse rate control,
      cardiac monitoring, reassessment, and electrical cardioversion if atrial
      fibrillation persisted. Patients who reverted to sinus rhythm were discharged
      with a cardiology follow-up within 3 days, whereas those still in atrial
      fibrillation were admitted. All cases were followed up for 6 months and adverse
      events recorded. RESULTS: Of the 153 patients, 75 were randomized to the ED
      observation unit and 78 to routine inhospital care. Eighty-five percent of ED
      observation unit patients converted to sinus rhythm versus 73% in the routine
      care group (difference 12%; 95% confidence interval [CI] -1% to 25%]; P=.06). The
      median length of stay was 10.1 versus 25.2 hours (difference 15.1 hours; 95% CI
      11.2 to 19.6; P<.001) for ED observation unit and inhospital care respectively.
      Nine ED observation unit patients required inpatient admission. Eleven percent of
      the ED observation unit group had recurrence of atrial fibrillation during follow
      up versus 10% of the routine inpatient care group (difference 1%; 95% CI -9% to
      11%; P=.93). There was no significant difference between the groups in the
      frequency of hospitalization or the number of tests, and the number of adverse
      events during follow-up was similar in the 2 groups. CONCLUSION: An ED
      observation unit protocol that includes electrical cardioversion is a feasible
      alternative to routine hospital admission for acute onset of atrial fibrillation
      and results in a shorter initial length of stay.

PMID- 18339450
TI  - Characterization of anti-Legionella activity of warnericin RK and delta-lysin I
      from Staphylococcus warneri.
AB  - Legionella pneumophila, the causative agent of Legionnaires' disease, is a
      waterborne bacteria. It can multiply in man-made water systems and infect people
      who inhale contaminated droplets. We have previously reported a Staphylococcus
      warneri strain that display an anti-Legionella activity. In this work, we
      characterized three anti-Legionella peptides that are produced by S. warneri. One
      peptide, warnericin RK, is original, while the two others are delta-lysin I and
      delta-lysin II, whose genes were previously described. Due to high sequence
      similarity of the two delta-lysins, further characterization was performed only
      on delta-lysin I. Warnericin RK and delta-lysin I displayed the same
      antibacterial spectrum, which is almost restricted to the Legionella genus. Also,
      both peptides have a hemolytic activity. These results led to the hypothesis that
      warnericin RK and delta-lysin I share a similar mode of action, and that
      Legionella should have a specific feature that may explain the high specificity
      of these antibacterial peptides.

PMID- 18339451
TI  - The diagnostic efficiency of biomarkers in sporadic Creutzfeldt-Jakob disease
      compared to Alzheimer's disease.
AB  - Laboratory markers have a prominent place among the diagnostic criteria for
      sporadic Creutzfeldt-Jakob disease (sCJD). Here we investigate the capability of
      protein 14-3-3, total-tau (t-tau), threonin-181-phosphorylated tau (p-tau), and
      neuron-specific enolase (NSE) in cerebrospinal fluid (CSF) together with the
      prion protein gene genotype to discriminate patients with sCJD (n=21) from
      neurological controls (n=164) and Alzheimer's disease (AD) patients (n=49). Low p
      tau/t-tau ratio was the best single marker for sCJD with 90% specificity against
      neurological controls at 86% sensitivity whilst NSE was the least accurate with
      79% sensitivity at 90% specificity. Many of the sCJD patients had extremely
      elevated t-tau values but normal values of the AD-marker p-tau. Protein 14-3-3
      was very sensitive (95%) although the specificity was relatively low (75%). A
      combination of elevated t-tau concentration with the presence of 14-3-3 protein
      in CSF gave the best test specificity of 96% at 84% sensitivity. We conclude that
      the combination of more than one CSF marker for neurodegeneration can improve the
      diagnostic test accuracy for sCJD against neurological controls including
      patients with other dementias.

PMID- 18339452
TI  - Abeta peptide conformation determines uptake and interleukin-1alpha expression by
      primary microglial cells.
AB  - Microglia clear amyloid beta (Abeta) after immunization. The interaction of Abeta
      with the microglial cell surface also results in cytokine expression. Soluble
      oligomers and protofibrils of Abeta may be more neurotoxic than Abeta fibrils. We
      investigated the effects of oligomeric, protofibrillar and fibrillar Abeta40 and
      Abeta42 peptides on uptake and IL-1alpha expression by primary microglia. Abeta
      peptide assemblies were extensively characterized. Primary microglial cells were
      exposed to different Abeta40 and Abeta42 assemblies and IL-1alpha expression was
      quantified. To study uptake, microglial cells were exposed to different
      assemblies of Cy3-labeled Abeta. We found that Abeta42 and Abeta40 oligomers and
      fibrils induced IL-1alpha expression, but protofibrils did not. We also observed
      that all forms of Abeta42 (oligomer, protofibril and fibril) and Abeta40 fibrils
      were taken up by the microglial cells. These results demonstrate that microglial
      cells can take up non-fibrillar Abeta and that oligomeric peptide induces an
      inflammatory response. The uptake of oligomeric and protofibrillar Abeta by
      microglia merits further investigation as a potential means for removing these
      neurotoxic species from the brain.

PMID- 18339453
TI  - Instability in the latency of P3a/P3b brain potentials and cognitive function in
      aging.
AB  - Instability in performance is a prominent feature of aging. In this study, 133
      participants evenly distributed across the adult lifespan underwent a three
      stimulus event-related potentials (ERPs) paradigm, and instability in P3a/P3b
      latency and reaction time (RT) were measured. P3a is related to alertness or
      reorientation of attention and it was elicited by distractor stimuli. P3b is
      related to controlled attentional processes and it was triggered by target
      stimuli. Maximum-likelihood estimation (MLE) was used to quantify the level of
      variability in latency across the single sweep ERPs. The results revealed
      increased variability in RT but not in P3a/P3b latency with age. Variability in
      P3a/P3b latency was related to executive functions, and variability in RT to
      speed. Generally, the relationships tended to increase with age. It can be
      concluded that increased variability in RT with age is caused by instability in
      processes related to response execution and possibly response selection, but not
      stimulus classification. Further, the results indicate that intraindividual
      variability is not a uniform concept, but has unique explanatory value at the
      neurophysiological and behavioral level.

PMID- 18339454
TI  - Synthesis and in vitro anti-bacterial evaluation of tetracyclic-ortho-fused 4H
      naphtho[1',2'-5,6]pyrano[3,4-d](1,2,3)selenadiazole and its derivatives.
AB  - Synthesis of new heterocyclic compounds 3a-e containing naphthopyran and
      selenadiazole as the heterocyclic sub-units in the molecule is achieved using
      high yielding synthetic protocol. These molecules 3a-e have shown moderate anti
      bacterial activity against some gram-positive and gram-negative bacterias.

PMID- 18339455
TI  - Synthesis and induction of G0-G1 phase arrest with apoptosis of 3,5-dimethyl-6
      phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)
      one.
AB  - The multistep synthesis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6
      dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one 15 has been carried out. The
      compound showed antiproliferative and apoptotic effects against K562, K562-R
      (imatinib mesilate resistant), HL60 and multidrug resistant (MDR) HL60 cell
      lines. Compound 15 showed a pro-apoptotic activity against HL60 and K562
      resistant cell lines markedly higher than etoposide and busulfan, respectively.
      Flow cytometry studies carried out on K562 cells allowed to establish that 15
      induces G0-G1 phase arrest followed by apoptosis.

PMID- 18339456
TI  - Synthesis of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines as a new class of
      antifilarial agents.
AB  - A series of 2-sulfanyl-6-methyl-1,4-dihydropyrimidines (8-21) were synthesized in
      good yields by alkylation of 5-methyl-6-phenyl-2-thioxo-1,2,3,6
      tetrahydropyrimidine-4-carboxylic acid ethyl esters (2-7) with different alkyl or
      aralkyl halides in the presence of a combination of anhydrous K(2)CO(3) and
      catalytic amount of tetrabutyl ammonium bromide. The title compounds were
      evaluated for their antifilarial activity against adult parasites of human
      lymphatic filarial parasite Brugia malayi (sub-periodic strain) in vitro and in
      vivo at various concentrations. One of the compounds (18) showed promising
      antifilarial activity.

PMID- 18339457
TI  - [Acitretin-induced pneumonia: an underestimated complication of treatment of
      psoriasis].
AB  - INTRODUCTION: Retinoids are known to induce side effects which can be severe.
      Alveolar and interstitial pneumonia of uncertain pathogenesis can rarely occur
      when retinoid are used among patients with psoriasis. EXEGESIS: We report an
      observation of acute respiratory distress beginning 26 days after introduction of
      acitretin, a second-generation retinoid. Treatment withdrawal and corticotherapy
      allow a spectacular amelioration of respiratory conditions. CONCLUSION: Pneumonia
      induced by retinoid must be known as a side effect of treatment of psoriasis.

PMID- 18339458
TI  - Retracing our STEP towards a successful CTL-based HIV-1 vaccine.

PMID- 18339460
TI  - Economics of polio vaccination in the post-eradication era: should OPV-using
      countries adopt IPV?
AB  - The continued use of oral polio vaccine (OPV) poses a threat to polio virus
      eradication. Stopping all polio vaccination in the post-certification era is no
      longer considered to be a practical option. Policy makers agree that OPV use must
      stop immediately after certification. Therefore, the pragmatic alternative is for
      the OPV-using countries to switch to IPV. This study estimates the cost of
      switching to IPV, and the cost-effectiveness of this switch. Using data on the
      number of polio cases and the number of unvaccinated children in different
      countries of the world, the risks of polio and polio outbreaks have been
      calculated. The current cost of routine and intensive OPV immunisation is about
      US $2143 million in the 148 OPV-using countries. Routine use of IPV in these
      countries should cost US $1246 million. If the current costs of routine and
      intensive polio immunisation are considered, adopting IPV to replace OPV will not
      increase the total global cost. Even if the cost of intensive polio immunisation
      is ignored, cost-effectiveness ratio of adopting IPV remains less than the
      average GNI per capita of OPV-using countries. The incremental cost of adopting
      IPV to replace OPV is relatively low, about US $1 per child per year, and most
      countries should be able to afford this additional cost.

PMID- 18339459
TI  - The relative contribution of antibody and CD8+ T cells to vaccine immunity
      against West Nile encephalitis virus.
AB  - West Nile virus (WNV) is a mosquito borne, neurotropic flavivirus that causes a
      severe central nervous system (CNS) infection in humans and animals. Although
      commercial vaccines are available for horses, none is currently approved for
      human use. In this study, we evaluated the efficacy and mechanism of immune
      protection of two candidate WNV vaccines in mice. A formalin-inactivated WNV
      vaccine induced higher levels of specific and neutralizing antibodies compared to
      a DNA plasmid vaccine that produces virus-like particles. Accordingly, partial
      and almost complete protection against a highly stringent lethal intracranial WNV
      challenge were observed in mice 60 days after single dose immunization with the
      DNA plasmid and inactivated virus vaccines, respectively. In mice immunized with
      a single dose of DNA plasmid or inactivated vaccine, antigen-specific CD8(+) T
      cells were induced and contributed to protective immunity as acquired or genetic
      deficiencies of CD8(+) T cells lowered the survival rates. In contrast, in
      boosted animals, WNV-specific antibody titers were higher, survival rates after
      challenge were greater, and an absence of CD8(+) T cells did not appreciably
      affect mortality. Overall, our experiments suggest that in mice, both inactivated
      WNV and DNA plasmid vaccines are protective after two doses, and the specific
      contribution of antibody and CD8(+) T cells to vaccine immunity against WNV is
      modulated by the prime-boost strategy.

PMID- 18339461
TI  - Discordance between antibody and T cell responses in recipients of trivalent
      inactivated influenza vaccine.
AB  - Thirty adults were tested for humoral and cellular immune responses following
      immunization with the trivalent inactivated influenza vaccine. Modest but
      significant inverse correlations between the baseline and the fold changes in the
      number of IFNgamma-producing cells and the levels of neutralizing antibodies were
      observed. Specific increases in proliferative responses in the CD8 CD45RA+
      population were noted after vaccination. Minimal correlations between
      neutralizing antibody titers and the number of IFNgamma-producing cells in terms
      of prevaccination levels or fold increases were observed. These results show
      specific increases in a CD8 T cell subset and discordant T and B responses
      induced by the trivalent inactivated influenza vaccine.

PMID- 18339462
TI  - The application of a weight of evidence approach to compare the quality of
      coastal sediments affected by acute (Prestige 2002) and chronic (Bay of
      Algeciras) oil spills.
AB  - To evaluate sediment quality in different areas affected by oil spills, a weight
      of evidence approach was employed by including a complete set of parameters as
      part of four lines of evidence: sediment contamination, biological effects
      (including biomarkers) and bioaccumulation under laboratory conditions, toxicity
      in field conditions and benthic community structure. The methodology was applied
      to sediments from the Bay of Algeciras (S Spain) chronically impacted by
      different spills, and the Galician Coast (NW Spain) acutely impacted by an oil
      spill (Prestige 2002). Results obtained have elucidated the sources and fates of
      pollutants and the type of risk involved for the ecosystem. Factorial analysis
      revealed that the main factors were those containing toxicity, chemistry and
      benthic community variables indicating degradation in Algeciras. It has been
      demonstrated that the impact associated with chronic event of contamination by
      oil spills are significantly more dangerous and polluted than those related to
      acute effects.

PMID- 18339463
TI  - Inorganic arsenic levels in baby rice are of concern.
AB  - Inorganic arsenic is a chronic exposure carcinogen. Analysis of UK baby rice
      revealed a median inorganic arsenic content (n=17) of 0.11 mg/kg. By plotting
      inorganic arsenic against total arsenic, it was found that inorganic
      concentrations increased linearly up to 0.25 mg/kg total arsenic, then plateaued
      at 0.16 mg/kg at higher total arsenic concentrations. Inorganic arsenic intake by
      babies (4-12 months) was considered with respect to current dietary ingestion
      regulations. It was found that 35% of the baby rice samples analysed would be
      illegal for sale in China which has regulatory limit of 0.15 mg/kg inorganic
      arsenic. EU and US food regulations on arsenic are non-existent. When baby
      inorganic arsenic intake from rice was considered, median consumption (expressed
      as microg/kg/d) was higher than drinking water maximum exposures predicted for
      adults in these regions when water intake was expressed on a bodyweight basis.

PMID- 18339464
TI  - Temporal trends of hydrocarbons in sediment cores from the Pearl River Estuary
      and the northern South China Sea.
AB  - Concentrations and fluxes of unresolved complex mixture of hydrocarbons (UCM) and
      polycyclic aromatic hydrocarbons (PAHs) were analyzed for two (210)Pb dated
      sediment cores from the Pearl River Estuary (PRE) and the adjacent northern South
      China Sea (NSCS). Compound-specific stable carbon isotopic compositions of
      individual n-alkanes were also measured for identification of the hydrocarbon
      sources. The historical records of PAHs in the NSCS reflected the economic
      development in the Pearl River Delta during the 20th century. PAHs in the NSCS
      predominantly derive from combustion of coal and biomass, whereas PAHs in the PRE
      are a mixture of petrogenic and pyrogenic in origins. The isotopic profiles
      reveal that the petrogenic hydrocarbons in the PRE originate predominantly from
      local spillage/leakage of lube oil and crude oils. The accumulation rates of
      pyrogenic PAHs have significantly increased, whereas UCM accumulation has
      slightly declined in the NSCS in the recent three decades.

PMID- 18339465
TI  - Age and the balance of emotions.
AB  - With age, the quality of emotions may shift from negative in tone to positive,
      but also from active to passive. The shift from negative to positive is
      consistent with the age as maturity perspective. The shift from active to passive
      supports the age as decline perspective. If these generalities are correct, then
      they should apply to positive emotions as well as negative emotions. We should
      see a shift in positive emotions from active (excitement) to passive (serenity),
      as well as in the negative emotions (from the agitation of anxiety and anger to
      the lethargy of depression). In order to accurately portray the shifts in
      emotional tone, age may best be considered as simultaneously indicating maturity
      and decline. This paper examines results from the emotions module of the 1996
      U.S. General Social Survey and finds support for the idea that age is associated
      with a shift from negative to positive and from active to passive emotions.

PMID- 18339466
TI  - Azucar y nervios: explanatory models and treatment experiences of Hispanics with
      diabetes and depression.
AB  - This study examined the explanatory models of depression, perceived relationships
      between diabetes and depression, and depression treatment experiences of low
      income, Spanish-speaking, Hispanics with diabetes and depression. A purposive
      sample (n=19) was selected from participants enrolled in a randomized controlled
      trial conducted in Los Angeles, California (United States) testing the
      effectiveness of a health services quality improvement intervention. Four focus
      groups followed by 10 in-depth semi-structured qualitative interviews were
      conducted. Data were analyzed using the methodology of coding, consensus, co
      occurrence, and comparison, an analytical strategy rooted in grounded theory.
      Depression was perceived as a serious condition linked to the accumulation of
      social stressors. Somatic and anxiety-like symptoms and the cultural idiom of
      nervios were central themes in low-income Hispanics' explanatory models of
      depression. The perceived reciprocal relationships between diabetes and
      depression highlighted the multiple pathways by which these two illnesses impact
      each other and support the integration of diabetes and depression treatments.
      Concerns about depression treatments included fears about the addictive and
      harmful properties of antidepressants, worries about taking too many pills, and
      the stigma attached to taking psychotropic medications. This study provides
      important insights about the cultural and social dynamics that shape low-income
      Hispanics' illness and treatment experiences and support the use of patient
      centered approaches to reduce the morbidity and mortality associated with
      diabetes and depression.

PMID- 18339467
TI  - Social services utilization by adults with intellectual disabilities and their
      families.
AB  - In this study, we used Andersen's Behavioral Model with the family as a unit of
      analysis to examine the patterns of awareness and utilization of social services
      by families with at least one adult with intellectual disabilities. Face-to-face
      interview questionnaires were conducted with primary family caregivers in Hsinchu
      City, Taiwan in 2004. Data were collected on adults' and caregivers'
      predisposing, enabling, and need variables as well as awareness and utilization
      of formal social services. A total of 792 interviews were completed, making a
      response rate of 94.2%. Multivariate logistic regression analysis was used to
      identify potential predictors of social service awareness and utilization. We
      found awareness and utilization to be mostly associated with predisposing and
      enabling variables including caregiver's socioeconomic status, family connection
      with social networks, and family participation in related groups or associations.
      Younger caregivers were more likely to access formal assistance, while adults
      whose families were more connected into social networks were more likely to be
      aware of in-kind and voucher services, e.g., in-home services including respite
      and home care, and vocational services such as sheltered workshops, and bus
      voucher services.

PMID- 18339468
TI  - Pro-inflammatory potential of ultrafine particles in mono- and co-cultures of
      primary cardiac cells.
AB  - Inhalation of particulate air pollution has been associated with increased risks
      for cardiovascular mortality and morbidity, but the underlying mechanisms are
      still under discussion. One possible pathway may be that inhaled particles cross
      the air-blood barrier and interact directly with cardiac tissue. The aim of the
      present study was to examine the pro-inflammatory potential of particles in
      cardiac cells. Mono- and co-cultures of primary adult male Wistar (Han) rat
      cardiomyocytes (CMs) and cardiofibroblasts (CFs) were exposed to increasing
      concentrations of ultrafine (<100nm) carbon black particles (Printex 90).
      Expression and release of cytokines (IL-6, IL-1beta and TNF-alpha) were measured
      by using quantitative real-time PCR and ELISA, respectively. Cytotoxicity was
      estimated by measuring cellular release of lactate dehydrogenase (LDH). A
      particle concentration-dependent increase in IL-6 release was observed in both CM
      mono- and co-cultures (EC(50) approximately 57microg/ml). Furthermore, IL-6
      levels detected in both control and particle-exposed co-cultures were
      synergistically increased compared to mono-cultures (10-19-fold, dependent on the
      exposure). Experiments with contact and non-contact co-cultures indicate that
      direct cellular contact is of key importance for the enhanced release of IL-6 in
      co-cultures. An apparent particle-induced release of IL-1beta was only detected
      in co-cultures. The release of TNF-alpha was low and did not seem notably
      influenced by particle exposure. Treatment with an IL-1 receptor antagonist
      apparently eliminated the particle-induced release of IL-6. In conclusion,
      ultrafine particles have a pro-inflammatory potential in primary cardiac cells.
      Furthermore, IL-1 seems critical in triggering particle-induced release of IL-6.
      These pro-inflammatory responses may be elicited when particles are translocated
      into the pulmonary circulation upon inhalation or administered intravascularly
      during medical procedures.

PMID- 18339469
TI  - Flexural strength of veneering ceramics for zirconia.
AB  - OBJECTIVES: The flexural strengths of veneering ceramics for zirconia were
      compared. METHODS: With 10 different veneering ceramics for zirconia (test group)
      and three different veneering ceramics for the metal-ceramic technique (control
      group) three-point flexural strength and biaxial flexural strength according to
      ISO 6872: 1995 as well as four-point flexural strength according to EN 843-1:
      2005 were measured (n=10). Statistical analysis was performed with one-way ANOVA
      and post hoc Scheffe test (SPSS, p<0.05). RESULTS: For the test group, three
      point flexural strength ranged between 77.8+/-8.7 and 106.6+/-12.5MPa without any
      statistically significant differences, biaxial flexural strength between 69.1+/
      4.8 and 101.4+/-10.5MPa with three homogeneous groups and four-point flexural
      strength between 59.5+/-6.2 and 89.2+/-9.5MPa with five homogeneous groups. The
      control group showed three-point flexural strength values ranging from 93.3+/
      13.5 to 149.4+/-20.5MPa, biaxial flexural strength values from 93.4+/-10.0 to
      141.2+/-11.6MPa, and four-point flexural strength values from 82.7+/-8.5 to
      116.9+/-9.8MPa. In every case, the results of the four-point flexure test were
      significantly lower than those obtained in the three-point flexure test. The
      three-point flexural strengths of the test group are similar to those of two
      ceramics of the control group. The flexural strength of one ceramic of the
      control group significantly exceeded the strengths of all other ceramics
      investigated. CONCLUSION: Three-point flexural strength values of veneering
      ceramics for zirconia are similar to those of veneering ceramics for the metal
      ceramic technique. The four-point flexure test among all three tests showed
      highest discrimination between the different ceramic materials.

PMID- 18339470
TI  - Proneness to hypomania predicts EEG coherence between left motor cortex and left
      prefrontal cortex.
AB  - Previous research has demonstrated that hypomania is associated with approach
      motivation and activity in the left prefrontal cortex (PFC). Other research has
      linked left motor cortex excitability to approach motivation, suggesting the
      existence of connections between the motor cortex and PFC. The present research
      extends this work using unilateral hand contractions to manipulate contralateral
      cortical activity, and examining the relationship between motor cortex and PFC
      inter-electrode EEG coherence and hypomania. Within the right-hand contraction
      condition, hypomania related to greater connectivity between the left motor
      cortex and left PFC, relative to connectivity between the left motor cortex and
      right PFC. No relationships were found within the left-hand condition. The
      present research provides additional support for the role of the left PFC in
      bipolar disorder, as well as an important extension of research linking motor
      cortex excitability to emotion and approach motivation.

PMID- 18339471
TI  - An analysis of assessment outcomes from eight years' operation of the Australian
      border weed risk assessment system.
AB  - The majority of Australian weeds are exotic plant species that were intentionally
      introduced for a variety of horticultural and agricultural purposes. A border
      weed risk assessment system (WRA) was implemented in 1997 in order to reduce the
      high economic costs and massive environmental damage associated with introducing
      serious weeds. We review the behaviour of this system with regard to eight years
      of data collected from the assessment of species proposed for importation or held
      within genetic resource centres in Australia. From a taxonomic perspective,
      species from the Chenopodiaceae and Poaceae were most likely to be rejected and
      those from the Arecaceae and Flacourtiaceae were most likely to be accepted.
      Dendrogram analysis and classification and regression tree (TREE) models were
      also used to analyse the data. The latter revealed that a small subset of the 35
      variables assessed was highly associated with the outcome of the original
      assessment. The TREE model examining all of the data contained just five
      variables: unintentional human dispersal, congeneric weed, weed elsewhere,
      tolerates or benefits from mutilation, cultivation or fire, and reproduction by
      vegetative propagation. It gave the same outcome as the full WRA model for 71% of
      species. Weed elsewhere was not the first splitting variable in this model,
      indicating that the WRA has a capacity for capturing species that have no history
      of weediness. A reduced TREE model (in which human-mediated variables had been
      removed) contained four variables: broad climate suitability, reproduction in
      less or than equal to 1year, self-fertilisation, and tolerates and benefits from
      mutilation, cultivation or fire. It yielded the same outcome as the full WRA
      model for 65% of species. Data inconsistencies and the relative importance of
      questions are discussed, with some recommendations made for improving the use of
      the system.

PMID- 18339472
TI  - Preoperative serum sex hormone-binding globulin as a predictive marker for
      extraprostatic extension of tumor in patients with clinically localized prostate
      cancer.
AB  - OBJECTIVES: We investigated the relationships of serum sex hormone-binding
      globulin (SHBG) level with known prognostic factors for prostate cancer in men
      who received radical retropubic prostatectomy (RRP) for clinically localized
      prostate cancer. METHODS: Preoperative serum levels of SHBG were analyzed in 288
      consecutive patients who were scheduled to undergo RRP for clinically localized
      prostate cancer. We investigated the potential associations of preoperative serum
      SHBG level with various clinical and pathological factors. Accuracy of variables
      in predicting adverse pathological features was assessed via receiver operator
      characteristics (ROC) curves. RESULTS: In univariate analysis, preoperative serum
      SHBG level was observed to be significantly associated with extraprostatic
      extension of a tumor (p=0.019) and with pathological Gleason score (p=0.001). In
      multivariate analysis, serum SHBG level (p=0.039) along with serum PSA (p<0.001)
      level, biopsy Gleason score (p<0.001), and clinical stage (p=0.004) was observed
      to be an independent predictor of the extraprostatic extension of prostate
      cancer. The area under ROC curve that demonstrated the performance of a
      multivariate logistic regression model (MLRM), which included serum SHBG level
      and other preoperative variables, in predicting extraprostatic extension of tumor
      was larger than that of MLRM without SHBG (0.797 vs. 0.758, p=0.121). Meanwhile,
      serum SHBG level was not observed to be significantly associated with
      pathological Gleason score in multivariate analysis (p=0.303). CONCLUSIONS: Our
      data showed that serum SHBG level is an independent predictive factor for
      extraprostatic extension of tumor in patients with clinically localized prostate
      cancer.

PMID- 18339473
TI  - Editorial comment on: preoperative serum sex hormone-binding globulin as a
      predictive marker for extraprostatic extension of tumor in patients with
      clinically localized prostate cancer.

PMID- 18339474
TI  - Re: Niels J. van Casteren, Hans Stoop, Gert R. Dohle, Ronald de Wit, J. Wolter
      Oosterhuis, Leendert H.J. Looijenga. Noninvasive detection of testicular
      carcinoma in situ in semen using OCT3/4. Eur Urol 2008;54:153-60.

PMID- 18339475
TI  - Continuous versus six months a year maximal androgen blockade in the management
      of prostate cancer: a randomised study.
AB  - OBJECTIVE: To evaluate systematically interrupted androgen suppression (SIAS) 6
      mo a year compared with continuous androgen suppression (CAS) in prostate cancer
      treatment. PATIENTS AND METHODS: All patients underwent maximal androgen blockade
      for 6 mo. Then, depending on the randomisation arm, they continued (CAS) or
      stopped their treatment for 6 mo before they resumed it a year later and so on
      (SIAS). Primary end points were patient's health-related quality of life (HQOL)
      and time to progression. Secondary end points were cancer-specific and overall
      survival. Progression was defined by a clinical event or PSA value exceeding
      double the value obtained at the end of the first 6 mo of therapy. RESULTS: Sixty
      two patients were randomised to CAS and 67 to SIAS. There were no significant
      differences between groups at baseline. Androgen suppression was associated with
      HQOL deterioration except for an improvement in urinary symptoms. The 6-mo off
      therapy period was not long enough to regain normal testosterone values. There
      was no difference in HQOL scores between CAS and SIAS except that men in the
      latter group reported a greater need for painkillers but a better ability to have
      an erection. Progression occurred in 62 patients (48.1%) with no significant
      difference between CAS and SIAS with a mean follow-up of 44.8 mo. Death occurred
      in 41 patients and specific death in 19 patients (10% and 19% of the CAS and SIAS
      groups, respectively). CONCLUSIONS: Although patients in the SIAS group were
      maintained off-therapy 50% of the time, insufficient testosterone recovery in
      this group likely explains why differences between the two groups were moderate
      or absent with regards to HQOL and survival, respectively.

PMID- 18339476
TI  - Editorial comment on: continuous versus six months a year maximal androgen
      blockade in the management of prostate cancer: a randomised study.

PMID- 18339477
TI  - Laparoscopic radical prostatectomy: ten years later, time for evidence-based
      foundation.

PMID- 18339478
TI  - Cognitive fMRI and neuropsychological assessment in patients with secondarily
      generalized seizures.
AB  - OBJECTIVES: Cognitive dysfunction is a frequent comorbid disorder in epilepsy
      which has been associated with high seizure frequency. We examined the effect of
      secondarily generalized tonic-clonic seizures (SGTCS) on cognitive dysfunction
      using neuropsychological assessment and fMRI. PATIENTS AND METHODS: Sixteen
      patients with localization-related epilepsy of varying etiologies and SGTCS
      underwent extensive neuropsychological assessment. Functional MRI was performed
      probing the frontal and temporal lobes with two paradigms aimed at investigating
      speed of mental processing and working memory. RESULTS: A high number of total
      lifetime SGTCS was associated with lower intelligence scores. Moreover, a trend
      towards cognitive decline related to the number of SGTCS was observed. A
      relatively increased prefrontal activation related to the number of SGTCS was
      demonstrated, plus a trend towards a decreased activation in the frontotemporal
      areas. CONCLUSION: High numbers of SGTCS are associated with a drop in
      intelligence scores and altered prefrontal brain activation. A shift from
      frontotemporal to prefrontal activation seems to have occurred, suggesting that a
      functional reorganization of working memory is induced by a high number of SGTCS.
      It remains uncertain if this reorganization reflects a compensation mechanism, or
      the underlying pathological processes of cognitive dysfunction.

PMID- 18339479
TI  - Simultaneous removal of metal ions and linear alkylbenzene sulfonate by combined
      electrochemical and photocatalytic process.
AB  - Combined electrochemical removal of Zn(++) and Ni(++) and photo-oxidation of
      linear alkylbenzene sulfonate (LAS) by suspended TiO(2) particles was
      investigated. The effect of different process variables such as current density,
      pH and liquid flow rate on the sole electrochemical reduction of metal ions was
      also evaluated. At pH of 5.0, the removal of Zn(++) increased by 28% with
      increases in the liquid flux from 0.0021 to 0.0172 m(3)m(-2)s(-1) while the
      removal of Ni(++) was only enhanced marginally. Under optimum operating
      conditions used in the present study (liquid flux=0.0172 m(3) m(-2) s(-1),
      current density=0.166 mA cm(-2), pH 5.0 and in the presence of LAS), Zn(++) and
      Ni(++) were reduced by 86 and 56%, respectively, over 7h of the sole
      electrochemical treatment. For the sole photocatalytic treatment of LAS at pH of
      5.0, a 60% LAS degradation was obtained. However, the liquid flow rate did not
      have any considerable effect on the LAS oxidation. Finally, in the combined
      photocatalytic-electrolytic process, the LAS degradation increased to 76%.
      Nonetheless, in the combined system the Zn(++) and Ni(++) removal remained at
      comparable levels to those obtained in the sole electrochemical system.

PMID- 18339480
TI  - Removal of methylene blue from wastewater using fly ash as an adsorbent by
      hydrocyclone.
AB  - The excessive release of color into the environment is a major concern worldwide.
      Adsorption process is among the most effective techniques for color removal from
      wastewater and fly ash has been widely used as an adsorbent. Therefore, this
      study was carried out to understand the adsorption behavior of methylene blue
      from aqueous systems onto fly ash using the continuous mode. Continuous mode
      sorption experiments were carried out to remove methylene blue from its aqueous
      solutions in hydrocyclone equipment. The experiments were performed at constant
      temperature and dimensions of hydrocyclone with variation of flows through the
      equipment, concentrations of methylene blue solutions and fly ash concentration,
      respectively. A maximum removal of 58.24% was observed at adsorbent dosage of 900
      mg/l at pH 6.75 for an initial methylene blue concentration of 65 mg/l.

PMID- 18339481
TI  - Temporal strategy for discriminating noxious from non-noxious electrical stimuli
      by cortical and thalamic neural ensembles in rats.
AB  - Considerable evidence supports that pain is encoded in a large, widespread
      network that consists of the thalamus, cortex, as well as limbic system. However,
      the temporal properties of the neural matrix in pain processing were largely
      unknown. In the present study, we simultaneously recorded thalamic and cortical
      neuronal discharges elicited by brief noxious or innocuous electrical stimulus in
      awake rats. The discrimination performance of the neural ensembles in
      differentiating noxious from innocuous inputs was calculated using different
      window sizes at the millisecond and second level, respectively. The results
      demonstrated that coding information emerged in a quantum-like manner; the
      minimum spike-train length for discriminating noxious from innocuous inputs was
      40 ms. The nociceptive coding activity was temporally dynamic, and could be
      preserved for a relatively long time (3-4 s) within the thalamocortical loops,
      independent of the initial brief stimuli. These results suggest that the
      nociceptive signals may be reverberatory within the thalamocortical loops, hence
      keeping the neurosignature for central pain representation.

PMID- 18339482
TI  - Occurrence of Anoplocephala perfoliata infection in horses in Ontario, Canada and
      associations with colic and management practices.
AB  - Infection with the tapeworm Anoplocephala perfoliata has been found to be
      associated with equine colic in horses in the United Kingdom. Using a matched
      case-control study design, data collected from 117 pairs of horses in Ontario
      were examined for evidence of associations between risk of colic and A.
      perfoliata infection, and between seropositivity to infection and management
      practices. Cases were horses in southern Ontario diagnosed with colic by local
      veterinarians, and control horses were from the same stables as cases and were
      matched by age, breed and gender where possible. Infection status was defined on
      the basis of positive results upon coprological examination, and/or
      seropositivity to a 12/13 kDa A. perfoliata secretory protein. Fifty-six percent
      of the 234 horses were seropositive for A. perfoliata, but eggs were found in
      samples from only 6% of horses. Horses dependent on pasture for a large part of
      their diet were significantly more likely to have ELISA optical density levels
      above 0.600 compared to other horses (odds ratio [OR]=6.38; p=0.029). This
      finding identified exposure to pasture as an important source of A. perfoliata
      infection in the horses used in the study. In a subset of 46 pairs of horses for
      which control horses had no known history of colic, a statistically significant
      negative association was found between the risk of colic and optical density (OD)
      levels >0.200-0.600, relative to OD levels < or = 0.090 (OR=0.08; p=0.017). There
      was no other statistical evidence of an association between the risk of colic and
      A. perfoliata infection.

PMID- 18339483
TI  - Intensive rotational grazing assists control of gastrointestinal nematodosis of
      sheep in a cool temperate environment with summer-dominant rainfall.
AB  - While rotational grazing methods have an accepted role in the management of
      gastrointestinal nematodosis (GIN) of small ruminants in humid tropical regions,
      their efficacy and application in cool temperate regions is more controversial.
      This study evaluated GIN over 2 years in three classes of fine wool Merino sheep
      (lambs, hoggets and ewes) under three different sheep management systems in a
      cool tableland environment near Armidale NSW Australia (950m altitude, 30 degrees
      31'S, 151 degrees 39'E). The management systems were High input (HI) with high
      fertiliser inputs, a target of 100% sown pasture, high stocking rate (13.4 dry
      sheep equivalents/ha) and relatively long grazing periods; Typical (TYP) New
      England management system with moderate fertiliser inputs and stocking rate
      (9.3DSE/ha) and relatively long grazing periods; and Intensive rotational grazing
      (IRG) with moderate fertiliser inputs and stocking rate (8.8DSE/ha) but very
      short (mean 5 days) grazing periods and long (mean 103 days) rest periods. Twenty
      sheep of each class in each management treatment were sampled monthly for faecal
      worm egg counts (WEC, followed by larval differentiation), and body weights with
      a blood sample taken for haematology every second month. The proportion of sheep
      with WEC above zero did not differ between management systems but the magnitude
      of WEC did, with sheep under IRG displaying lower mean WEC than those on the
      other treatments (IRG: 326, HI: 594, TYP: 536, eggs/g P<0.0001). This was despite
      a significantly longer mean interval between anthelmintic treatments (IRG: 144
      days, HI: 77 days, TYP: 78 days, P<0.0001). The IRG management system also
      influenced the composition of the infections with sheep on this treatment having
      a significantly lower proportion of Haemonchus contortus in their faecal cultures
      (IRG: 59.7%, HI: 79.4%, TYP: 80.9%, P<0.05) and a significantly higher proportion
      of Trichostrongylus spp. Sheep on the IRG treatment also had a significantly
      higher haematocrit (HCT) than those on the other management systems. Despite the
      lower WEC and higher HCT, sheep under IRG also had significantly lower
      bodyweights and fleece weights overall, although this was only evident in sheep
      raised to adulthood prior to the experiment, not those raised during the 2-year
      experimental period. The results demonstrate that IRG systems with short grazing
      periods and long rest periods between grazing events can assist with control of
      GIN in cool temperate climates where H. contortus is the dominant parasite.

PMID- 18339484
TI  - Host-dependent variations in the seasonal prevalence and intensity of heterophyid
      encysted metacercariae (Digenea: Heterophyidea) in brackish water fish in Egypt.
AB  - The prevalence of heterophyid (Digenea: Heterophyidae) encysted metacercariae
      (EMC) in its second intermediate host, the fish Mugil spp. and Tilapia spp. was
      studied in a subtropical permanent Lake in northeastern Egypt. Seasonal changes
      in the occurrence of the EMC in different fish hosts were monitored in a
      longitudinal field survey lasting 12 months from June 2006 to May 2007. This
      study tested two hypotheses; (i) prevalence and intensity of heterophyid EMC
      fluctuate seasonally throughout the year and (ii) variation in the prevalence and
      intensity of heterophyid EMC is host-dependent. A total of 832 fish specimens
      comprising 5 species collected from Manzala Lake, northeastern Egypt were
      examined by artificial gastric juice digestion for EMC. All five species of
      brackish water fish examined were found to harbor the EMC of the family
      Heterophyidae in their muscles. The overall infection prevalence of EMC over 12
      months was 23.2%. The adult flukes recovered from puppies experimentally infected
      with morphologically different metacercariae from different fish species were
      compatible with six species belong to five genera of Heterophyidae, namely,
      Heterophyes heterophyes, Heterophyes aequalis, Pygidiopsis genata, Phagicola sp.,
      Haplorchis sp. and Stictodora sp. EMC of H. heterophyes were most abundant,
      detected in 56% of the total fish examined. P. genata was ranked second, followed
      by Phagicola sp., H. aequalis, Haplorchis sp., and Stictodora sp., respectively.
      Seasonal differences in infection were observed for all heterophyid species
      studied in all fish species examined. Heterophyid infections reached peak
      prevalences during the summer season 38.2% followed by spring 26.6% and autumn
      19.3% seasons, whereas the lowest prevalence was recorded in the winter 8.7%.
      Intensity of heterophyid EMC followed the same seasonal pattern, being high
      during summer months and low in winter months. All fish species were infected
      with all the heterophyid digeneans, but with different prevalence. Possible
      reasons for these findings are discussed with reference to host, climatic and
      biotic factors.

PMID- 18339485
TI  - Selective cholinergic lesions in the rat nucleus basalis magnocellularis with
      limited damage in the medial septum specifically alter attention performance in
      the five-choice serial reaction time task.
AB  - Selective immunotoxic cholinergic lesions in the nucleus basalis magnocellularis
      (NBM) impair visuospatial attention performance in a 5-choice serial reaction
      time task (5-CSRT task). The features of the reported deficits, however, do not
      perfectly match among studies, in which some lesions may have been too weak while
      others largely encroached onto the septal region. Using the 5-CSRT task, we
      therefore re-assessed the effects of NBM lesions that produced minimal septal
      damage. Long-Evans adult male rats were trained to stable 5-CSRT task performance
      (stimulus duration: 0.5 s) and subsequently subjected to intra-NBM injections of
      192 IgG-saporin (200 ng/side). The lesions induced more than 90% loss of choline
      acetyltransferase-positive neurons in the NBM vs. only 28% in the medial septum.
      The decrease of the optical density of acetylcholinesterase reaction products was
      significant in the cortex (-91%), not in the hippocampus. In the 5-CSRT task, the
      lesions resulted in increased omissions (from 10% to 30%) and decreased correct
      responses (from 80% to 60%), with negligible or no effects on all other usually
      collected variables. This deficit disappeared with lengthened stimulus duration
      (i.e. 0.5-1 and then 5 s). Furthermore, overall performance levels decreased when
      the stimulus duration was shortened (i.e. 0.5-0.2 s) or its intensity attenuated,
      and rats with cholinergic lesions remained consistently impaired vs. controls.
      These results show that disruption of sustained visual attention functions by
      damage to the NBM cholinergic neurons can be evidenced despite weak or no effects
      on variables accounting for motivational, locomotion- or impulsivity-related
      biases. Discrepancies with previously reported results are discussed in terms of
      differences in lesion extent/specificity and training levels.

PMID- 18339486
TI  - Colocalization of C4d deposits/CD68+ macrophages in rheumatoid nodule and
      granuloma annulare: immunohistochemical evidence of a complement-mediated
      mechanism in fibrinoid necrosis.
AB  - Rheumatoid nodule (RN) represents a palisading granuloma with central fibrinoid
      necrosis, which is not only a classical manifestation of rheumatoid arthritis
      (RA) and part of the American College of Rheumatology (ACR)-criteria, but also is
      its diagnostic hallmark. The pathogenesis of RN is still not fully understood. At
      present, only data on serum analyses indicating a complement-mediated
      pathogenesis in the development of RA are available. Equivalent examinations for
      RN have not yet been performed. Granuloma annulare (GA) represents another type
      of palisading granuloma. A special subtype of GA, subcutaneous GA (SGA), is an
      important differential diagnosis to RN. Therefore, our aim was to examine RN and
      SGA regarding the complement deposition (C4d) by immunohistochemical means. All
      RN and GA were stained by hematoxylin/eosin and different special stains. In
      addition, all specimens were stained immunohistochemically with antibodies
      against CD68. Five GA and five RN were analyzed immunohistochemically with
      antibodies against C4d and CD68, and evaluated using single- and doublestaining
      immunohistochemistry. All RN and GA displayed depositions of C4d within their
      central necroses and between the surrounding palisading macrophages. Most
      importantly, C4d/CD68 double staining was visible in the palisading macrophages
      next to the necroses, while macrophages in the periphery were negative for C4d
      but positive for CD68. The main difference between RN and GA was a quantitative
      phenomenon with less positively reacting macrophages in a more incomplete
      palisade in GA. The positive reactions of all central necroses to C4d and
      colocalization of CD68 and C4d suggest that a complement-mediated mechanism may
      be operative in the formation of fibrinoid necrosis. This mechanism may be
      involved in any form of "fibrinoid necrosis", since no different patterns of
      C4d/CD68 expression could be observed in GA. This may explain why RG/GA are not
      distinguishable morphologically.

PMID- 18339487
TI  - The effect of changing technique, dose, and PTV margin on therapeutic ratio
      during prostate radiotherapy.
AB  - PURPOSE: To quantify the dosimetric and radiobiological changes seen when using
      intensity-modulated radiation therapy (IMRT) or planning target volume (PTV)
      margin reduction with consistent planning parameters in a representative sample
      of localized prostate cancer patients. METHODS AND MATERIALS: Twenty patients
      were randomly selected from a cohort that received 79.8 Gy using six-field
      conformal radiotherapy. Using the clinical contours, PTV margin, planning system,
      and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and
      88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to
      3 mm. These plans were then compared using various dosimetric and radiobiological
      endpoints calculated for various alpha/beta. RESULTS: Intensity-modulated RT
      resulted in greater conformity to the PTV (p < 0.001). No improvement in mean
      normal tissue complication probabilities in the rectal wall (NTCPrw) was seen,
      and the modified therapeutic ratio (TR(mod)) was largely unchanged between six
      field conformal and IMRT for the majority of the patients. When IMRT was used to
      escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p <
      0.001). Reducing the posterior PTV margin from 7 mm to 3 mm for an IMRT plan
      reduced the mean NTCPrw by 12% (p < 0.001) and resulted in a trend toward
      increased TR(mod)(p = 0.005). Changes in TR(mod) between conformal and IMRT
      planning or PTV reduction showed large interpatient variability. CONCLUSIONS:
      Changing from conformal to IMRT, or from PTV(10-7) to PTV(3), did not produce a
      uniform interpatient increase in TR(mod)when the CTV contained the prostate
      alone. Radiobiological benefits of these two methods seem to be dependent on the
      particular anatomy of individual patients, supporting the use of patient-specific
      margin, planning, and dose prescription strategies.

PMID- 18339488
TI  - Selecting patients for exclusive permanent implant prostate brachytherapy: the
      experience of the Paris Institut Curie/Cochin Hospital/Necker Hospital group on
      809 patients.
AB  - PURPOSE: The aim of this study was to analyze overall and relapse-free survival
      in a cohort of 809 patients, 34% of whom corresponded to a higher-risk group than
      American Brachytherapy Society (ABS) criteria. METHODS AND MATERIALS: Between
      January 1999 and September 2004, 809 patients were treated with permanent loose
      125 iodine seed implantation (IsoSeed Bebig, Eckert and Ziegler) by the Paris
      Institut Curie, Cochin Hospital, and Necker Hospital group. Of these 809
      patients, 533 (65.9%) corresponded exactly to ABS criteria. Two hundred and
      seventy-six patients (34.1%) had a prostate-specific antigen (PSA) level between
      10 and 15, or a Gleason score of 7, or both (non-ABS group). RESULTS: Overall 5
      year survival was 98%, with no difference between the ABS group and the non-ABS
      patient subgroups (p = 0.62).Five-year relapse-free survival was 97% in the ABS
      group; it was significantly lower (p = 0.001) in the non-ABS group but remained
      satisfactory at 94%. On subgroup analysis, the results appeared to be better for
      the subgroup of patients with PSA 10-15 than for the subgroup with a Gleason
      score of 7. CONCLUSIONS: Our results suggest that selected patients in the
      intermediate-risk group of localized prostate cancers can be safely proposed as
      recipients of permanent implant brachytherapy as monotherapy.

PMID- 18339489
TI  - Association between tangential beam treatment parameters and cardiac
      abnormalities after definitive radiation treatment for left-sided breast cancer.
AB  - PURPOSE: To examine the association between radiation treatment (RT) parameters,
      cardiac diagnostic test abnormalities, and clinical cardiovascular diagnoses
      among patients with left-sided breast cancer after breast conservation treatment
      with tangential beam RT. METHODS AND MATERIALS: The medical records of 416
      patients treated between 1977 and 1995 with RT for primary left-sided breast
      cancer were reviewed for myocardial perfusion imaging and echocardiograms. Sixty
      two patients (62/416, 15%) underwent these cardiac diagnostic tests for
      cardiovascular symptoms and were selected for further study. Central lung
      distance and maximum heart width and length in the treatment field were
      determined for each patient. Medical records were reviewed for cardiovascular
      diagnoses and evaluation of cardiac risk factors. RESULTS: At a median of 12
      years post-RT the incidence of cardiac diagnostic test abnormalities among
      symptomatic left-sided irradiated women was significantly higher than the
      predicted incidence of cardiovascular disease in the patient population, 6/62
      (9%) predicted vs. 24/62 (39%) observed, p = 0.001. As compared with patients
      with normal tests, patients with cardiac diagnostic test abnormalities had a
      larger median central lung distance (2.6 cm vs. 2.2 cm, p = 0.01). Similarly,
      patients with vs. without congestive heart failure had a larger median central
      lung distance (2.8 cm vs. 2.3 cm, p = 0.008). CONCLUSIONS: Contemporary RT for
      early breast cancer may be associated with a small, but potentially avoidable,
      risk of cardiovascular morbidity that is associated with treatment technique.

PMID- 18339490
TI  - Lifecourse socioeconomic predictors of midlife drinking patterns, problems and
      abstention: findings from the 1958 British Birth Cohort Study.
AB  - BACKGROUND: Research suggests that outcomes associated with drinking may differ
      depending upon patterns of consumption, drinking related symptoms and social
      problems. This paper investigated socioeconomic predictors (measuring multiple
      indices, period and consistency of disadvantage) of midlife drinking patterns.
      METHODS: Socioeconomic information from the 1958 British Birth Cohort Study
      (n=9146) included: manual socioeconomic position and owner/buyer residential
      tenure (7, 11, 16, 33 and 42 y), and educational attainment (33 y). At 45 y, the
      overlap between drinking patterns was explored using the Alcohol Use Disorders
      Identification Test. Patterns included: 'Moderate-binge' (binge drinkers with low
      problem scores, consuming within UK sensible drinking weekly guidelines); Low
      Problem Heavy (LPH) drinkers (regardless of binge); 'Problem' (and heavy or
      binge) and 'Non-/occasional' (< or =monthly) drinkers. These categories were
      compared to 'Low-risk' drinkers. RESULTS: Socioeconomic disadvantage was
      consistently associated with moderate-binge, non-/occasional and problem but not
      LPH drinking. The highest risk was associated with multiple and persistent
      disadvantage across childhood and adulthood; this risk was partially accounted
      for education. Non-/occasional and moderate-binge drinking was predicted by
      disadvantage during childhood alone. The socioeconomic disadvantage of non
      /occasional drinkers was not explained by past problem or heavy drinking.
      CONCLUSIONS: Socioeconomic disadvantage across the lifecourse was consistently
      linked to specific drinking patterns. Furthermore, associations linking
      socioeconomic disadvantage with drinking patterns will typically be
      underestimated if multiple and persistent disadvantage is not investigated. The
      role of persistent socioeconomic disadvantage in the poor health of non-drinkers
      and moderate-binge drinkers needs investigation. The findings support current
      initiatives targeting the reduction of social and individual costs associated
      with specific drinking patterns.

PMID- 18339491
TI  - Smoking tobacco along with marijuana increases symptoms of cannabis dependence.
AB  - AIM: User practices/rituals that involve concurrent use of tobacco and marijuana 
      smoking blunts and "chasing" marijuana with tobacco - are hypothesized to
      increase cannabis dependence symptoms. DESIGN: Ethnographers administered group
      surveys to a diverse, purposive sample of marijuana users who appeared to be 17
      35 years old. SETTING: New York City, including non-impoverished areas of
      Manhattan, the transitional area of East Village/Lower East Side, low-income
      areas of northern Manhattan and South Bronx, and diverse areas of Brooklyn and
      Queens. PARTICIPANTS: 481 marijuana users ages 14-35, 57% male, 43% female; 27%
      White, 30% Black, 19% Latino, 5% Asian, 20% of other/multiple race. MEASUREMENTS:
      Among many other topics, group surveys measured cannabis dependence symptoms;
      frequencies of chasing, blunt smoking, joint/pipe smoking, using marijuana while
      alone, and general tobacco use; and demographic factors. FINDINGS: Blunt smoking
      and chasing marijuana with tobacco were each uniquely associated with five of the
      seven cannabis dependence symptoms. Across symptoms, predicted odds were 2.4-4.1
      times greater for participants who smoked blunts on all 30 of the past 30 days
      than for participants who did not smoke blunts in the past 30 days. Significant
      increases in odds over the whole range of the five-point chasing frequency
      measure (from never to always) ranged from 3.4 times to 5.1 times. CONCLUSIONS:
      Using tobacco with marijuana - smoking blunts and "chasing" marijuana with
      tobacco - contributes to cannabis dependence symptoms. Treatment for cannabis
      dependence may be more effective it addresses the issue of concurrent tobacco
      use.

PMID- 18339492
TI  - Controversies of fetal cardiac intervention.
AB  - Remarkable advances in ultrasound imaging technology have made it possible to
      diagnose fetal cardiovascular lesions as early as 12-14 weeks of gestation and to
      assess their physiological relevance by echocardiography. Moreover, invasive
      techniques have been developed and refined to relieve significant congenital
      heart disease (CHD), such as critical aortic and pulmonary stenoses in the
      pediatric population including neonates. Recognition of the fact that certain
      CHDs can evolve in utero, and early intervention may improve the outcome by
      altering the natural history of such conditions has led to the evolution of a new
      fetal therapy, i.e. fetal cardiac intervention. Two entities, pulmonary valvar
      atresia and intact ventricular septum (PA/IVS) and hypoplastic left heart
      syndrome (HLHS), are associated with significant morbidity and mortality even
      with postnatal surgical therapy. These cases are believed to occur due to
      restricted blood flow, leading to impaired growth and function of the right or
      left ventricle. Therefore, several centers started the approach of antenatal
      intervention with the primary goal of improving the blood flow through the
      stenotic/atretic valve orifices to allow growth of cardiac structures. Even
      though centers with a reasonable number of cases seem to have improved the
      technique and the immediate outcome of fetal interventions, the field is
      challenged by ethical issues as the intervention puts both the mother and the
      fetus at risk. Moreover, the perceived benefits of prenatal treatment have to be
      weighed against steadily improving postnatal surgical and hybrid procedures,
      which have been shown to reduce morbidity and mortality for these complex heart
      defects. This review is an attempt to provide a balanced opinion and an update on
      fetal cardiac intervention.

PMID- 18339493
TI  - Disposition of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) and its metabolite 4
      bromo-2-hydroxy-5-methoxyphenethylamine in rats after subcutaneous
      administration.
AB  - The psychedelic compound 4-bromo-2,5-dimethoxyphenethylamine (2C-B) has appeared
      as an agent in drug abuse or overdose cases in humans. The human pharmacokinetics
      of this drug is unknown and only partial information is available on its
      metabolites. Our experimental study was focused on the disposition and kinetic
      profile of 2C-B in rats after subcutaneous administration using a GC-MS validated
      method. One of the major metabolites 4-bromo-2-hydroxy-5-methoxyphenethylamine
      (2H5M-BPEA) was confirmed in rat tissues of lung, brain, liver and was
      quantitatively evaluated as well. The disposition of 2C-B was characterized by
      its estimated half-life 1.1h and estimated volume of distribution 16L/kg. The
      lung susceptibility for drug retention and gradual temporal release parallel to
      the brain were ascertained. The drug penetrating the blood/brain barrier was
      without significant delay. 2C-B brain to serum ratio attained a maximum value of
      13.9 and remained over the value of 6.5 to the end of our observation (6h after
      the dose). The distribution of the hydroxylated metabolite 2H5M-BPEA into the
      lipophilic brain tissue was less efficient in relation to the parent compound.
      The kinetics of the drug partitioning between blood to brain may be important for
      the subsequent assessment of its psychotropic or toxic effects.

PMID- 18339494
TI  - Sucrose stearate-based proniosome-derived niosomes for the nebulisable delivery
      of cromolyn sodium.
AB  - A Novel approach was developed for the preparation of controlled release
      proniosome-derived niosomes, using sucrose stearates as non-ionic biocompatible
      surfactants for the nebulisable delivery of cromolyn sodium. Conventional
      niosomes were prepared by a reverse phase evaporation method followed by the
      preparation of proniosomes by spraying the optimized surfactant-lipid mixture of
      sucrose stearate, cholesterol and stearylamine in 7:3:0.3 molar ratio onto the
      surface of spray dried lactose powder. Proniosome-derived niosomes were obtained
      by hydrating proniosomes with 0.9% saline at 50 degrees C and mixing for
      approximately 2 min. All vesicles were evaluated for their particle size,
      morphological characteristics, entrapment efficiency, in vitro drug release,
      nebulisation efficiency and physical stability at 2-8 degrees C. In addition,
      coating carrier surface with the surfactant-lipid mixture, during preparation of
      proniosomes, resulted in smaller, free flowing, homogenous and smooth vesicles
      with high drug entrapment efficiency. Compared to a standard drug solution, a
      successful retardation of the drug release rate was achieved with the proniosome
      derived niosomes, where the t50% value of the release profile was 18.1h compared
      to 1.8h. Moreover, high nebulisation efficiency percentage and good physical
      stability were also achieved. The results are very encouraging and offer an
      alternative approach to minimize the problems associated with conventional
      niosomes like degradation, sedimentation, aggregation and fusion.

PMID- 18339495
TI  - Involvement of monoamines and proinflammatory cytokines in mediating the anti
      stress effects of Panax quinquefolium.
AB  - Panax quinquefolium (PQ) is well acclaimed in literature for its effects on
      central and peripheral nervous system. The present study explores the effects of
      PQ on stress induced changes of corticosterone level in plasma, monoamines (NA,
      DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus
      regions of brain and also indicate their possible roles in modulating stress.
      Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed
      significant increase in plasma corticosterone level and depletion of
      noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex
      and hippocampal regions along with an increased level of IL-2 and IL-6 in the
      same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and
      200mg/kg p.o. prior to the stress regimen and its effects on selected stress
      markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was
      found to be effective in normalizing the CUS induced elevation of plasma
      corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly
      effective in reinstating the CUS induced depletion of NA, DA and 5-HT in
      hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of
      100mg/kg p.o. was found ineffective in regulating any of these CUS induced
      changes. Present study provides an insight into the possible role of PQ on
      hyperactive HPA axis in the regulation of immediate stress effectors like
      corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as
      a potential therapeutic in the cure of stress related disorders and needs to be
      evaluated in clinical studies to ascertain its efficacy.

PMID- 18339496
TI  - Toxicity studies on dermal application of plant extract of Plumbago zeylanica
      used in Ethiopian traditional medicine.
AB  - Plant-based therapeutic preparations are cyclically returning to complement
      dermatologic therapy, however, data on the toxicity profile of such plants are
      lacking. In the present study, Plumbago zeylanica, a medicinal plant commonly
      used in Ethiopia for skin diseases was subjected to a systematic dermatotoxicity
      study. To this effect, the dermatotoxicity of 80% methanol extract of the root
      part of Plumbago zeylanica was investigated in animals following standard
      procedures for irritation, sensitization, acute toxicity and repeated toxicity
      tests. Extraction of plant material with 80% methanol resulted in 9.45% of crude
      extract of Plumbago zeylanica. The skin irritation test on rabbits showed
      Plumbago zeylanica extract to be a moderate irritant, with a primary irritation
      index of 2.00. Sensitization test on mice by the Mouse Ear Swelling Test method
      revealed the extract to be non-sensitizer in a dose range of 4-10mg/ml and the
      percent responder was zero. Acute dermal toxicity test on rats did not produce
      any overt signs of toxicity, except that there was a weight gain difference
      between the test and control groups of female rats. This was not, however,
      supported by other parameters, like the absolute and relative organ weights.
      Repeated dose toxicity test was associated with increased relative testis weight
      (P<0.05) as well as higher values for Blood urea nitrogen and K+ (P<0.05) in both
      sexes with the highest dose (1000 mg/kg) group, although histopathological
      analyses failed to lend support to these observations. Taken together, the
      dermatotoxicity test results from this study suggest that Plumbago zeylanica
      toxic effects might be limited to effects like moderate irritation.

PMID- 18339497
TI  - [An atypical presentation of visceral leshmaniasis in an immunocompetent
      patient].

PMID- 18339498
TI  - [Streptococcus suis meningitis after oral contamination?].

PMID- 18339499
TI  - [Candida albicans urinary tract infection complicated by renal papillary necrosis
      and fungus balls].

PMID- 18339500
TI  - [A sexually transmitted peritonitis].

PMID- 18339501
TI  - [Profile and management of patients consulting for a non severe exacerbation of
      chronic obstructive pulmonary disease (Pragma survey)].
AB  - OBJECTIVES: To evaluate, in patients with chronic obstructive pulmonary disease
      (COPD), stage 0 or 1, the percentage of patients who had spirometry, and to study
      their sociodemographic, clinical and epidemiological characteristics. PATIENTS
      AND METHODS: An epidemiological survey was conducted with 2389 general
      practitioners concerning 4769 patients with early COPD, consulting for the first
      time for exacerbation of COPD, presumed to be bacterial. RESULTS: Spirometry
      under stable conditions was performed in only 30% of patients. When the physician
      does not have access to this examination to guide antibiotic prescription for an
      exacerbation presumed to be bacterial, recent guidelines have established a
      correlation between dyspnoea and the degree of severity of COPD (GOLD
      classification). This correlation was not confirmed by the present study: 34% of
      patients with stage 0 or 1 COPD complained of dyspnoea and 52% of patients with
      stage 2 or 3 COPD did not complain of dyspnoea. The main criterion in favour of a
      bacterial cause of exacerbation, frank purulent sputum, observed in one out of
      three patients, did not influence the decision to prescribe antibiotics, given to
      98% of patients. Therapy used bronchodilators (73%), even in patients with no
      signs of obstruction, and inhaled steroids (72%), although, according to
      guidelines, they are only indicated in the most serious forms (stage 3). This
      survey illustrates the effort needed to ensure better concordance between
      guidelines and practice, by taking into account the difficulties encountered by
      practitioners.

PMID- 18339502
TI  - [Brucella prostatic abscess].

PMID- 18339503
TI  - Image quality in conventional lumbar spine radiography: evaluation using the post
      processing tool Diamond View.
AB  - Conventional radiography contributes for the majority of examinations in
      radiology departments. Based on the European Commission Quality Criteria we
      evaluated the effects on image quality when applying the new post-processing tool
      Diamond View (Siemens AG Medical Solutions, Germany) to conventional lumbar spine
      radiographs. 100 digital image pairs in two directions in two planes of lumbar
      spine radiographs were prospectively evaluated by two radiologists. Statistical
      analysis was performed with a p-value<.05 considered as significant. Images were
      evaluated on basis of the modified imaging Quality Criteria by the Commission of
      the European Communities, rated on a five-point scale. Statistical analysis
      showed an overall tendency for improved image quality of Diamond View (DV) for
      all criteria. Significant differences could be found in most of the criteria.
      Additional phantom analyses supported the advantage of DV. In conclusion DV
      improves image quality in conventional lumbar spine radiographs.

PMID- 18339504
TI  - Imaging of the opacified middle ear.
AB  - Middle ear opacification on imaging studies performed in a non-traumatic setting
      mostly reflects chronic inflammatory/infectious disease. In some of these
      patients an underlying cholesteatoma will be found. High-resolution computed
      tomography examinations and magnetic resonance imaging are often used in the work
      out of the disease. High-resolution computed tomography of the opacified middle
      ear serves to describe the status of the ossicular chain, and its suspensory
      apparatus, as well as the status of the tympanic and mastoid wall. When ossicular
      erosions are visualized, the probability of a present cholesteatoma is about 90%.
      Whereas high-resolution computed tomography is not able to differentiate
      cholesteatoma from other types of opacification, magnetic resonance imaging is.
      The combined use of delayed post-Gd T1-weighted images and non-EPI based DWI
      seems to be the actual best option on this matter.

PMID- 18339505
TI  - Simultaneous determination of Ciprofloxacin and the active metabolite of
      Prulifloxacin in aqueous human humor by high-performance liquid chromatography.
AB  - A rapid and simple method for determining two fluoroquinolones (FQNs), namely
      Ciprofloxacin and Ulifloxacin, this being the last active metabolite of
      Prulifloxacin, in aqueous human humor (AHH) has been developed and validated. The
      calibration data resulted linearly correlated in the 4-500 ng/mL concentration
      range with 8 ng/mL lower limit of quantification (LLOQ) for Ciprofloxacin, and 5
      600 ng/mL concentration range with 6 ng/mL LOD for Ulifloxacin. The proposed
      analytic procedure has been validated by testing quality control sample (QCS) of
      AHH probed with the two FQNs at 10, 50, 500, and 1000 ng/mL concentration values.
      Validation of the method has been checked by accuracy and precision data of intra
      day and long-term experiments. The two FQN concentrations have been measured by
      HPLC technique with UV detection at 278-nm wavelength for the AHH of patients to
      whom were supplied oral doses of FQNs (500 mg) twice in a day, within 1-24h
      before the surgery intervention of cataract. The average concentration of
      Ciprofloxacin resulted 186 ng/mL and that of Ulifloxacin 78 ng/mL. The nice
      quality of the proposed analytic procedure means that it may be suitable for in
      vivo studies of pharmacokinetics regarding these substances in the AHH medium.

PMID- 18339506
TI  - Photochemical stabilities of some dihydropyridine calcium-channel blockers in
      powdered pharmaceutical tablets.
AB  - Photostabilities of some dihydropyridine calcium-channel blockers in pulverized
      pharmaceutical tablets were studied. Powdered tablets including amlodipine,
      nifedipine, or nilvadipine were exposed to D65 daylight lamp radiation according
      to an ICH guideline (ICH Q1B). The photodegradation of pharmaceutical components
      and their degradation products were monitored by HPLC using a reversed phase
      column with UV detection; their peak components were identified using MS
      analysis. Photochemical reactions involved in the photodegradation of these
      pharmaceuticals include aromatization of the dihydropyridine moiety and
      conversion to nitroso group from the nitro group in benzene rings. Chemical
      stability studies of these drugs indicate that nifedipine is the most
      photosensitive. The rate constant of nifedipine is indicated as seven times
      higher than those of the other two drugs.

PMID- 18339507
TI  - Evaluation of the susceptibility trends to meropenem in a nationwide collection
      of clinical isolates in Japan: a longitudinal analysis from 2002 to 2006.
AB  - The meropenem susceptibility surveillance study was performed between 2002 and
      2006 in Japan. Meropenem resistance against Pseudomonas aeruginosa was nearly
      constant at about 10% during the period. For all species of the bacteria tested,
      the MIC(90) of meropenem in 2006 was not more than 4-fold higher than that in
      2002 and 2004.

PMID- 18339508
TI  - Detection of daptomycin-nonsusceptible strains using the Neo-Sensitab
      prediffusion method.
AB  - Two prediffusion methods with daptomycin (DAP) Neo-Sensitabs were evaluated
      against a challenge set of 30 Staphylococcus aureus isolates and 30 enterococci.
      DAP Neo-Sensitabs were prediffused for either 8 or 20 h on Mueller-Hinton agar.
      Inhibition zones were plotted versus Etest MIC values determined on the same
      prediffused agar. A generalization to the genus level of the manufacturer's
      suggested Neo-Sensitabs breakpoints for staphylococci and enterococci was used to
      interpret the results. DAP-susceptible and DAP-nonsusceptible enterococci,
      Enterococcus faecium in particular, were not reliably discriminated using a 20-h
      prediffusion method and the manufacturer's suggested breakpoints. Further
      development of this testing methodology, such as changing the format to a
      susceptibility screen followed by a confirmatory MIC, is needed to accurately
      categorize the DAP susceptibility of enterococcal isolates. Prediffusion for
      either 8 or 20 h with DAP Neo-Sensitabs discriminated between susceptible and
      nonsusceptible S. aureus with minimal errors. Both prediffusion methods also
      detected changes in MIC values between isogenic pairs of susceptible and
      nonsusceptible S. aureus. These results suggest that a multisite evaluation of
      either prediffusion method with DAP Neo-Sensitabs against a larger collection of
      S. aureus is warranted.

PMID- 18339509
TI  - Effect of porin loss on the activity of tigecycline against Klebsiella pneumoniae
      producing extended-spectrum beta-lactamases or plasmid-mediated AmpC-type beta
      lactamases.
AB  - Tigecycline showed excellent in vitro activity against 50 clinical isolates of
      Klebsiella pneumoniae producing extended-spectrum beta-lactamases, plasmid
      mediated AmpC-type beta-lactamases, or both. This activity was not affected by
      porin loss. Porin loss, however, did affect the activity of imipenem against
      strains that expressed both types of enzymes.

PMID- 18339511
TI  - Developmental expression of glycine receptor subunits in rat cerebellum.
AB  - The distribution of the glycine receptor subunits alpha1-3 and beta in the
      developing rat cerebellum was studied from postnatal day 1 to adulthood by means
      of quantitative RT-PCR and immunohistochemistry. qRT-PCR of postnatal cerebella
      indicated the presence of mRNA for each subunit, with a relative expression of
      alpha2>alpha3>alpha1>beta. The immunohistochemistry indicated a strong alpha2
      signal in the Purkinje cells, internal and external granular layers. The alpha1-3
      subunits had weak signals in the Purkinje cells and molecular layer. The alpha1
      subunit was expressed at a low level and was also found in the white matter. The
      function of these receptors in neuronal and glial plasma membranes in early
      postnatal development remains to be determined.

PMID- 18339512
TI  - Delivering sensitive health care information: challenging the taboo of women's
      sexual health after pelvic radiotherapy.
AB  - OBJECTIVE: The aim of this study was to elicit current practice with regard to
      the content and delivery of patient education for women undergoing pelvic
      radiotherapy. METHODS: A 38-item questionnaire was sent to all radiotherapy
      departments (n=65) and a convenience sample of specialist gynaecological oncology
      nurses (n=166), with response rates of 62% (n=40) and 42% (n=52), respectively.
      Data analysis of 32 different patient education leaflets from individual cancer
      units, cancer networks and vaginal dilator manufacturers was conducted. Content
      was evaluated on the inclusion and accuracy of the key knowledge women should
      receive before completing pelvic radiotherapy. RESULTS: Patient education focused
      on the technical aspects of vaginal dilation with minimal content on psychosocial
      6% (n=2) or sexual health components 44% (n=14). It was evident from the
      information leaflets reviewed and questionnaire responses that there was
      duplication of verbal and written information provision in the clinical setting
      as opposed to using different information strategies to provide more
      comprehensive coverage of knowledge gaps in post-treatment sexual rehabilitation.
      CONCLUSION: Results suggest the provision of vaginal dilation advice and sexual
      health information may benefit from being placed in the wider context of
      assessing treatment impact on women's health. PRACTICE IMPLICATIONS: It is
      important to analyse the management of sensitive content, within both written
      information materials and verbal consultations, to determine the most effective
      information provision strategies that support sexual health interventions in
      cancer practice.

PMID- 18339513
TI  - The risk of gallbladder cancer from polyps in a large multiethnic series.
AB  - BACKGROUND: The aim of this study is assess whether patients with Indian ethnic
      background are at an increased risk of developing gallbladder cancer (GBC) if
      they have been diagnosed with ultrasonic abnormalities of the gallbladder.
      METHODS: Between January 1998 and July 2006, 137,655 abdominal ultrasound
      examinations were performed in Leeds Teaching Hospitals NHS Trust. After the
      exclusion of repeat scans and those performed for renal or pelvic disease, 71,431
      reports were included in this analysis. Patients in whom the diagnosis of GBC has
      been made without histology have been identified from the database of Northern
      and Yorkshire Cancer Registry and the presence of GBC was correlated with
      ultrasonic gallbladder abnormalities. RESULTS: Gallbladder polyps (GBP) were
      detected in 3.3% of patients and these were larger than 10 mm in 0.1% of the
      cases. Age above 60 years, Indian ethnic background, single GBP larger than 10mm,
      the presence of gallstones, severe gallbladder wall thickening and irregular
      thickening were independently associated with the higher odds of developing GBC.
      The prevalence of malignancy in those with GBP was significantly higher among
      patients with Indian ethnic background compared to Caucasian patients, 5.5%
      versus 0.08%, p<0.001. CONCLUSIONS: The presence of GBP, irrelevant of size,
      amongst patients of Indian ethnic decent, is an indication for further
      investigation and/or cholecystectomy.

PMID- 18339514
TI  - High-fat diet may impair K(ATP) channels in vascular smooth muscle cells.
AB  - K(ATP) channel in vascular smooth muscle cell (VSMC) is closely linked to the
      etiology of hypertension. The aim of this study was to investigate effect of the
      high-fat diet-induced obesity on K(ATP) channel and blood pressure. Obesity was
      induced by a 24-week high-fat diet feeding in rats. Function and expression of
      K(ATP) channel in mesenteric arteries were examined using myography system, patch
      clamp and Western blotting. We show that high-fat diet increased blood pressure,
      decreased K(ATP) channel-mediated relaxation responses and currents, and down
      regulated K(ATP) expression in VSMC. In conclusion, diet-induced obesity impairs
      K(ATP) channels in VSMC, which may underscore obesity-triggered increase in blood
      pressure.

PMID- 18339516
TI  - Exploring the role of metacognition in obsessive--compulsive and anxiety
      symptoms.
AB  - This study tests three hypotheses, predicting first that metacognition is highly
      correlated with anxiety and obsessive-compulsive (O-C) symptoms, second that it
      mediates the relationship between O-C symptoms and anxiety, and third that the
      meta-cognitive predictors of anxiety are different from the meta-cognitive
      predictors of O-C symptoms. The sample of the present study was 850 students
      selected from various universities in Turkey. Significant correlations between
      metacognition, O-C symptoms and anxiety were observed. Also, mediation analysis
      confirmed that metacognition fully mediated the relationship between O-C symptoms
      and anxiety. Consistent with our hypothesis, trait anxiety and O-C symptoms had
      different meta-cognitive predictors. Although, we expected that meta-cognitive
      beliefs would vary based on the sub-type of O-C symptoms, meta-cognitive beliefs
      did not differ according to the O-C symptom subtypes. We discussed results with
      reference to the literature of meta-cognition, anxiety and O-C symptoms.

PMID- 18339515
TI  - Verbal fluency performance in amnestic MCI and older adults with cognitive
      complaints.
AB  - Verbal fluency tests are employed regularly during neuropsychological assessments
      of older adults, and deficits are a common finding in patients with Alzheimer's
      disease (AD). Little extant research, however, has investigated verbal fluency
      ability and subtypes in preclinical stages of neurodegenerative disease. We
      examined verbal fluency performance in 107 older adults with amnestic mild
      cognitive impairment (MCI, n=37), cognitive complaints (CC, n=37) despite intact
      neuropsychological functioning, and demographically matched healthy controls (HC,
      n=33). Participants completed fluency tasks with letter, semantic category, and
      semantic switching constraints. Both phonemic and semantic fluency were
      statistically (but not clinically) reduced in amnestic MCI relative to
      cognitively intact older adults, indicating subtle changes in the quality of the
      semantic store and retrieval slowing. Investigation of the underlying constructs
      of verbal fluency yielded two factors: Switching (including switching and
      shifting tasks) and Production (including letter, category, and action naming
      tasks), and both factors discriminated MCI from HC albeit to different degrees.
      Correlational findings further suggested that all fluency tasks involved
      executive control to some degree, while those with an added executive component
      (i.e., switching and shifting) were less dependent on semantic knowledge.
      Overall, our findings highlight the importance of including multiple verbal
      fluency tests in assessment batteries targeting preclinical dementia populations
      and suggest that individual fluency tasks may tap specific cognitive processes.

PMID- 18339517
TI  - Immunohistochemical and in-situ hybridization study of hypoxia inducible factor
      1alpha and angiopoietin-1 in a rabbit model of mandibular distraction
      osteogenesis.
AB  - The endogenous release of angiogenic factors in a rabbit mandibular distraction
      osteogenesis model was investigated. The spatial and temporal expression of
      hypoxia inducible factor-1alpha (HIF-1alpha) and angiopoietin-1 (Ang-1) was
      compared at different phases. The lengthened calluses were harvested on post
      osteotomy days 13, 20, 34 and 48, and then stained with haematoxylin & eosin.
      Immunohistochemical (IHC) and in-situ hybridization (ISH) examination of HIF
      1alpha and Ang-1 staining was performed. The ossification in the distracted gap
      was predominantly intramembranous and slightly endochondral. Expression of HIF
      1alpha and Ang-1 was mainly detected in the cytoplasm of fibroblast-like cells,
      osteoblasts and immature osteocytes on day 13 and 20, but declined with bone
      maturation. HIF-1alpha was also detected in the nuclei of some osteoblasts. These
      results suggest that the production of HIF-1alpha and Ang-1 in the distracted gap
      may contribute to new bone formation during gradual distraction of the mandible.

PMID- 18339518
TI  - Improvement of osseointegration of titanium dental implant surfaces modified with
      CO ions: a comparative histomorphometric study in beagle dogs.
AB  - The aim of this study was to compare carbon-oxygen (CO) ion implantation as a
      surface treatment with diamond-like carbon and commercially treated implants,
      including double acid-etched (Osseotite), oxidized (TiUnite) and sandblasted and
      acid-etched (SLA), using machine-turned titanium implants as control. A total of
      72 dental implants divided into 6 groups were placed in the mandibles of 12
      beagle dogs. Evaluation was performed by conventional light transmission
      microscopy and environmental scanning electron microscopy (ESEM). The
      histological results obtained via ESEM demonstrated bone-implant contact
      percentage (%BIC) for implants treated with CO ion implantation of 61% and 62% at
      3 and 6 months, respectively. At the same time points, the values were 48% and
      45% for double acid-etched, 46% and 52% for sandblasted and acid-etched, 55% and
      46% for oxidized, and 33% and 49% for machine-turned titanium control implants.
      Values of %BIC were statistically significantly higher in implants treated with
      CO ion implantation compared to the commercially treated implant group (p=0.002
      and p=0.025) and the control implants (p=0.001 and p=0.032) at 3 and 6 months,
      respectively. No significant differences were observed between the three groups
      of commercially treated implants. The larger %BIC of the ion-implanted group was
      observable at an early stage.

PMID- 18339519
TI  - Large intraparotid facial nerve schwannoma: case report and review of the
      literature.
AB  - Here is reported an extremely rare case of a large intraparotid facial nerve
      schwannoma in a 32-year-old female who presented with a parotid mass. There had
      been a long clinical course and sudden onset of facial weakness. Diagnostic
      evaluation and surgical management are discussed along with a brief review of the
      literature.

PMID- 18339520
TI  - Transthoracic hernia after harvesting a costal and latissimus dorsi flap.
AB  - Ribs are one of the most widely used grafts in craniofacial surgery. Harvesting a
      costochondral graft is easy and safe. The main complications are related to
      pneumothorax and chest-wall deformity in children. A complication is described in
      a patient who underwent an orbito-zygomatic reconstruction with two contiguous
      ribs and a latissimus dorsi free flap, and who subsequently developed a
      transthoracic hernia that required reconstruction with polypropylene mesh.

PMID- 18339521
TI  - Factors associated with utilization of healthcare resources among epilepsy
      patients.
AB  - PURPOSE: To determine those variables associated with utilization of healthcare
      resources in epilepsy patients. METHODS: We interviewed 256 epilepsy patients.
      Target variables included the number of clinic visits, ER visits and in-patient
      admissions over the past year and AEDs currently being used. Predictor variables
      were age, race/ethnicity, marital status, education, income, insurance, seizure
      frequency and QOLIE-10 results. We used univariate analysis to determine those
      factors associated with the target variables and multivariate analysis to
      ascertain those independently significant. RESULTS: On univariate analysis,
      higher seizure frequency and poorer QOLIE-10 scores were associated with the
      number of clinic visits, ER visits and in-patient admissions. Increased seizure
      frequency and male gender were associated with higher use of AEDs. Using ordinal
      logistic regression, QOLIE-10 scores was the only variable associated with the
      number of clinic visits. Both seizure frequency and QOLIE-10 scores were
      independently associated with the number of in-patient admissions while seizure
      frequency and male gender remained independently associated with AED use. Using
      binary logistic regression, QOLIE-10 scores and seizure frequency were
      independently associated with the number of ER visits. CONCLUSION: Seizure
      frequency and quality of life are major factors associated with utilization of
      healthcare resources in epilepsy patients.

PMID- 18339522
TI  - Molecular basis and clonal nature of increasing pneumococcal macrolide resistance
      in South Africa, 2000-2005.
AB  - The prevalence and molecular epidemiology of pneumococcal macrolide resistance in
      South Africa was investigated. Minimum inhibitory concentrations and serotypes of
      pneumococcal isolates causing invasive disease from 2000-2005 (n=15982),
      collected through a national laboratory-based surveillance system, were
      determined. Randomly selected isolates from 2005 (51%; 260/508) had resistance
      mechanisms determined, and clonality was investigated by pulsed-field gel
      electrophoresis (PFGE) (n=64) and multilocus sequence typing (n=7). Macrolide
      resistance increased from 9% (160/1828) in 2000 to 14% (508/3656) in 2005
      (P<0.001). Serotype 14 was the most common macrolide-resistant serotype (40%;
      760/1921). The majority of macrolide-resistant isolates (75%; 1437/1921)
      displayed the macrolide-lincosamide-streptogramin B (MLS(B)) phenotype. Of the
      strains screened genotypically, 57% (147/260) contained erm(B), 27% (71/260)
      contained mef(A) and 15% (40/260) contained erm(B) and mef(A); 1% (2/260)
      contained ribosomal mutations. Macrolide-resistant isolates were predominantly
      penicillin-non-susceptible and multidrug-resistant. Isolates clustered according
      to serotype by PFGE, and 22% (14/64), 11% (7/64) and 5% (3/64) of isolates were
      related to the Taiwan(19F)-14, England(14)-9 and Spain(9V)-3 global clones,
      respectively. Routine use of the 7-valent pneumococcal conjugate vaccine (PCV-7)
      could reduce the burden of macrolide-resistant pneumococcal disease in South
      Africa.

PMID- 18339523
TI  - Carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates from
      Turkey with OXA-48-like carbapenemases and outer membrane protein loss.
AB  - Treatment options are limited in infections caused by extended-spectrum beta
      lactamase (ESBL)-producing Enterobacteriaceae, with carbapenems generally
      preferred. Disturbingly, however, carbapenem-resistant strains are emerging
      worldwide. Here we report two clinical isolates, one Escherichia coli and one
      Klebsiella pneumoniae, each with high-level carbapenem resistance (imipenem
      minimum inhibitory concentration of 32 microg/mL). They were isolated following
      imipenem therapy from two hospital patients who had received imipenem therapy in
      different regions of Turkey. Both isolates produced OXA-48-like carbapenemases,
      enzymes so far reported only from Turkey. Both isolates also had group 1 CTX-M
      type ESBLs and had lost major outer membrane proteins. OXA-48-like carbapenemases
      appear to be scattered in Turkey and surveillance to determine their prevalence
      is warranted.

PMID- 18339524
TI  - Metastatic gastrointestinal stromal tumour presenting as hypercalcaemia--a rare
      occurrence.

PMID- 18339525
TI  - Pentoxifylline to treat radiation proctitis: a small and inconclusive randomised
      trial.
AB  - This prospective randomised controlled study of 40 patients could not show a
      statistically significant advantage with 6 months of pentoxifylline compared with
      standard measures for late radiation-induced rectal bleeding. However, a modest
      benefit cannot be excluded and larger randomised placebo-controlled trials with
      longer durations of pentoxifylline treatment may be justified.

PMID- 18339526
TI  - Pharmacokinetic studies of a Chinese triple herbal drug formula.
AB  - Yin Chen Hao Tang preparation (YCHTP) is a classic traditional Chinese medicine
      formula, which is commonly used for clinical treatment of hepatological diseases.
      In this study, a rapid and validated high-performance liquid chromatography
      (HPLC) method was developed to simultaneously identify 6,7-dimethylesculetin and
      geniposide in rat plasma. This assay was performed on a Dikma Diamonsil RP(18)
      column (200 mm*4.6 mm, 5 MUm) with acetonitrile-methanol-water (0.1% formic acid)
      as the mobile phase, showing acceptable linearity, intra- and inter-day precision
      and accuracy (R.S.D.=5%), and absolute recovery for two analytes (74%); the
      limits of quantitation were 0.4 and 1.12 MUg/ml, and the limits of detection were
      0.06 and 0.09 MUg/ml for two analytes. The developed method was successfully
      applied to study the effect of formula compatibility on the pharmacokinetics of
      6,7-dimethylesculetin and geniposide in YCHTP when orally administrating an
      effective human daily dose of YCHTP to rats. We surmise that formula
      compatibility can significantly influence the pharmacokinetics of YCHTP, and we
      have elucidated and validated the compatible administration of YCHTP.

PMID- 18339527
TI  - A comparable, chemical and pharmacological analysis of the traditional Chinese
      medicinal herbs Oldenlandia diffusa and O. corymbosa and a new valuation of their
      biological potential.
AB  - The herb of Oldenlandia diffusa (Willd.) Roxb. (Family Rubiaceae) is well-known
      in Chinese folk medicine for the treatment of hepatitis and malignant tumors of
      the liver, lung and stomach. However, another herb of O. corymbosa (L.) Lam is
      also used interchangeably in South China for treating the same conditions. To
      compare the efficacy of the two herbs, the antiproliferative effect of their
      extracts and the antiangiogenic activity of their main constituents were
      appraised. The Sulforhodamine B (SRB) assay in human hepatoma HepG2 cells and
      human colon carcinoma CaCo2 cells and the zebrafish angiogenic model were used
      for this purpose. The results showed almost no antiproliferative effect of the
      methanol extracts from O. diffusa and O. corymbosa, while the chloroform extracts
      exhibited slightly antiproliferative effects. The main components had almost no
      effect on zebrafish angiogenic vessel formation at the concentrations tested. The
      results suggest that the mechanism of antitumor activity of O. diffusa may not be
      attributed to the antiproliferative and antiangiogenic effects.

PMID- 18339528
TI  - Role of airway epithelial cells in development of asthma and allergic rhinitis.
AB  - Asthma and allergic rhinitis frequently coexist in the same patient. There is a
      similarity and variation as well as potential relationship between asthma and
      allergic rhinitis. There is an increasing evidence to suggest a major involvement
      of airway epithelial cells in the pathogenesis of asthma and allergic rhinitis.
      The present review describes the importance of the airway epithelial cell in the
      development of allergic airway diseases, its role as the primary airway defense
      against exposure of the airway and lung to inflammatory stimuli and antigens and
      as an important player through activation of epithelial Toll-like receptors
      (TLRs) to provide an important link between innate immunity and allergic disease.
      Additionally, airway epithelial cells can act as inflammatory promoters capable
      of directing dendritic cells (DCs) towards a T helper 2 (Th2) response, and as
      active producers of several inflammatory/anti-inflammatory mediators. It is
      hypothesized that airway epithelial cells may play as both inflammatory initiator
      and immuno-pathological feedback regulation between allergic rhinitis and asthma
      via release of systemic inflammatory mediators. Thus, airway epithelial cells may
      be valuable therapeutic targets for discovery and development of new drugs and/or
      new therapeutic strategies to treat asthma and allergic rhinitis.

PMID- 18339529
TI  - ALOX5 promoter genotype and response to montelukast in moderate persistent
      asthma.
AB  - BACKGROUND: It was hypothesized that asthmatic patients with mutant alleles in
      the leukotriene pathway should not respond to leukotriene receptor antagonists
      and the concept of a tailored treatment is increasingly supported. METHODS: Sixty
      one patients (mean age 24.9 years, range 14-52) with moderate persistent asthma
      were clinical and immunological assess prior and after a 6-month treatment with
      montelukast. Tandem repeat polymorphisms were genotyped in the promoter (-147 to 
      176) of 5-lipoxygenase gene (ALOX5). RESULTS: Thirty-two patients (52.5%) were
      homozygous for the five repeats allele; 17 (27.9%) were heterozygous (4/5
      repeats) and 12 (19.7%) were homozygous for 4/4 repeats. After the montelukast
      treatment decrease number of asthma exacerbations, improvement of FEV(1) and
      decreased use of beta(2) agonists was observed in patients with 5/5 or 4/5
      repeats. Conversely, the patients with 4/4 repeats genotype did not modify these
      data after treatment. CONCLUSIONS: It was confirmed that ALOX5 promoter
      polymorphisms have a clear influence in montelukast response in atopic moderate
      persistent asthma patients. The genetic study could identify those patients most
      likely to respond to montelukast.

PMID- 18339530
TI  - An international collaborative pathologic study of surgical lung biopsies from
      mustard gas-exposed patients.
AB  - BACKGROUND: Recent studies have shown strong evidence that bronchiolitis
      obliterans is the major long-term sequelae of exposure to sulfur mustard (SM).
      This study is the first to examine the histopathologic spectrum of changes in a
      large number of surgical lung biopsies from patients exposed to SM. METHOD:
      Fifteen patients with chronic respiratory disease from mustard gas exposure were
      divided into severe (6 cases) and mild exposure (9 cases). All had surgical (open
      or thoracoscopic) lung biopsy, pulmonary function tests (PFTs) and chest high
      resolution computed tomography scan (HRCT). RESULT: The mean age of the cases was
      43.8+/-9.6 (range 33-65). All patients had dyspnea and cough as the two main
      complaints. Only one patient was a smoker. Thirteen patients had normal PFTs,
      while one had obstruction and one had mild restriction. Six (66.6%) patients in
      the mild exposure and 3 (50%) in the severe exposure group showed evidence of
      more than 25% air trapping on chest HRCT. Among the mild group, 3 had features of
      constrictive bronchiolitis and another had features suggestive of this
      (bronchiolectasis and mucus stasis). The next most common finding was a mild-to
      moderate chronic cellular bronchiolitis (3 patients). Two among the 6 in the
      severe group showed constrictive bronchiolitis and one showed features suggestive
      of constrictive bronchiolitis. CONCLUSION: We conclude that about half of
      patients had diagnostic constrictive bronchiolitis, or bronchiolectasis and mucus
      stasis consistent with more proximal luminal compromise. The fact that there were
      no differences between the low- and high-dose groups suggests that effects of SM
      are not solely dependent on the severity of exposure. The results also indicate
      that the diagnosis of chronic lung disease due to SM may be difficult. Surgical
      lung biopsy may be helpful in difficult cases, as constrictive (obliterative)
      bronchiolitis can be present in symptomatic patients with normal PFTs and chest
      HRCT.

PMID- 18339531
TI  - Wnt/beta-catenin signaling: new (and old) players and new insights.
AB  - Wnt/beta-catenin signaling has central roles in embryogenesis and human diseases
      including cancer. A central scheme of the Wnt pathway is to stabilize the
      transcription coactivator beta-catenin by preventing its phosphorylation
      dependent degradation. Significant progress has been made toward the
      understanding of this crucial regulatory pathway, including the protein complex
      that promotes beta-catenin phosphorylation-degradation, and the mechanism by
      which the extracellular Wnt ligand engages cell surface receptors to inhibit beta
      catenin phosphorylation-degradation. Here we review some recent discoveries in
      these two areas, and highlight some crucial questions that remain to be resolved.

PMID- 18339532
TI  - Carbon post-microarrays for glucose sensors.
AB  - A novel design and fabrication method of glucose sensors based on high aspect
      ratio carbon post-microarrays is reported in this paper. Apart from the fact that
      carbon has a wide electrochemical stability window, a major advantage of using
      carbon post-microarrays as working electrodes for an amperometric glucose sensor
      is the large reactive surface per unit footprint substrate area, improving
      sensitivity of the glucose sensor. The carbon post-microarrays were fabricated by
      carbon-microelectromechanical systems (C-MEMS) technology. Immobilization of
      enzyme onto the carbon post-electrodes was carried out through co-deposition of
      glucose oxidase (GOx) and electrochemically polymerized polypyrrole (PPy).
      Sensing performance of the glucose sensors with different post-heights and
      various post-densities was tested and compared. The carbon post-glucose sensors
      show a linear range from 0.5mM to 20mM and a response time of about 20s, which
      are comparable to the simulation result. Sensitivity per unit footprint substrate
      area as large as 2.02mA/(mMcm(2)) is achieved with the 140microm high (aspect
      ratio around 5:1) carbon post-samples, which is two times the sensitivity per
      unit footprint substrate area of the flat carbon films. This result is consistent
      with the hypothesis that the number of reaction sites scales with the reactive
      surface area of the sensor. Numerical simulation based on enzymatic reaction and
      glucose diffusion kinetics gives the optimum geometric design rules for the
      carbon post-glucose sensor. Glucose sensors with even higher sensitivity can be
      achieved utilizing higher carbon post-microarrays when technology evolution will
      permit it.

PMID- 18339533
TI  - Surface plasmon resonance biosensor detects the downstream events of active
      PKCbeta in antigen-stimulated mast cells.
AB  - Surface plasmon resonance (SPR) biosensors detect large changes of angle of
      resonance (AR) when RBL-2H3 mast cells are cultured on a sensor chip and
      stimulated with antigen. However, the detail of molecular events that are
      responsible for such large changes of AR remained unknown. In this study, we
      investigated the relationship between intracellular signaling events induced by
      antigen and the change of AR, by genetic manipulation of intracellular signaling
      molecules; spleen tyrosine kinase (Syk), src-like adaptor protein (SLAP), linker
      for activation of T cells (LAT), growth-factor-receptor-bound protein 2 (Grb2),
      Grb2-related adaptor protein (Gads), and isotypes of protein kinase C (PKC). RBL
      2H3 mast cells overexpressing dominant-negative Syk or SLAP, which both interfere
      with active Syk, exhibited only minimal increase of AR in response to antigen
      stimulation. Likewise, the interference of the activation of LAT and Gads, by
      expressing dominant-negative LAT and Gads, respectively, resulted in nearly
      complete suppression of the antigen-induced increase of AR. The cells
      overexpressing PKCs, apart from PKCbeta, showed a reduced extent of increase of
      AR in response to antigen stimulation. Moreover, the introduction of the small
      interfering RNA targeted against PKCbeta suppressed the antigen-induced increase
      of AR. These results indicate that the activation of Syk, LAT, Gads, and
      subsequent PKCbeta is indispensable for the antigen-induced increase of AR of
      mast cells detected by SPR biosensors.

PMID- 18339534
TI  - Electrochemical determination of uric acid at ordered mesoporous carbon
      functionalized with ferrocenecarboxylic acid-modified electrode.
AB  - Ordered mesoporous carbon (OMC) functionalized with ferrocenecarboxylic acid (Fc)
      was used to modify the glassy carbon (GC) electrode. The characterization of OMC
      Fc shows that, after anchoring ferrocene on the mesoporous, ordered mesostructure
      of the material (OMC-Fc) remains intact and Fc is electrochemically accessible.
      The obtained OMC-Fc-modified electrode was used to investigate the
      electrochemical behavior of uric acid (UA). UA oxidation is catalyzed by this
      electrode in aqueous buffer solution (pH 7.3) with a decrease of 200mV in
      overpotential compared to GC electrode. The detection and determination of UA in
      the presence of ascorbic acid (AA), the main interferent, were achieved. The
      voltammetric signals due to UA and AA were well separated with a potential
      difference of 308mV, a separation that can allow the simultaneous determination
      of UA and AA. With amperometric method, at a constant potential of 375mV, the
      catalytic current of UA versus its concentration shows a good linearity in the
      range 60-390microM (R=0.998) with a detection limit of 1.8microM (S/N=3). These
      results are not influenced by the presence of AA in the sample solution. With
      good stability and reproducibility, the present OMC-Fc-modified electrode was
      applied in the determination of UA content in urine sample and satisfactory
      results were obtained.

PMID- 18339535
TI  - CYP450 biosensors based on gold chips for antiepileptic drugs determination.
AB  - Three-electrode configuration chips containing a Pt, Au and a screen-printed
      Ag/AgCl as counter, working and reference electrode, respectively, have been
      developed. Selective determination of Phenobarbital (PB) has been carried out by
      Cytochrome P450 2B4 (CYP450) immobilization into a polypyrrole matrix onto the
      gold working electrode. Chronoamperometric experiments show a PB diffusion
      coefficient of 2.42x10(-6)cm(2)s(-1), a reproducibility and repeatability in
      terms of residual standard deviation (RSD) of 13% and 5.51%, respectively, and a
      limit of detection (LOD) of 0.289 micromol dm(-3) (alpha=beta=0.05) for the
      developed CYP450-biosensor chip. Its performance has been showed by the
      determination of PB in pharmaceutical drugs. HPLC has been used as reference
      technique.

PMID- 18339536
TI  - Electrochemical impedance spectroscopy for study of aptamer-thrombin interfacial
      interactions.
AB  - A simple and highly sensitive electrochemical impedance spectroscopy (EIS)
      biosensor based on a thrombin-binding aptamer as molecular recognition element
      was developed for the determination of thrombin. The signal enhancement was
      achieved by using gold nanoparticles (GNPs), which was electrodeposited onto a
      glassy carbon electrode (GCE), as a platform for the immobilization of the
      thiolated aptamer. In the measurement of thrombin, the change in interfacial
      electron transfer resistance of the biosensor using a redox couple of
      [Fe(CN)(6)](3-/4-) as the probe was monitored. The increase of the electron
      transfer resistance of the biosensor is linear with the concentration of thrombin
      in the range from 0.12nM to 30nM. The association and dissociation rate constants
      of the immobilized aptamer-thrombin complex were 6.7x10(3)M(-1)s(-1) and 1.0x10(
      4)s(-1), respectively. The association and dissociation constants of three
      different immobilized aptamers binding with thrombin were measured and the
      difference of the dissociation constants obtained was discussed. This work
      demonstrates that GNPs electrodeposited on GCE used as a platform for the
      immobilization of the thiolated aptamer can improve the sensitivity of an EIS
      biosensor for the determination of protein. This work also demonstrates that EIS
      method is an efficient method for the determination of association and
      dissociation constants on GNPs modified GCE.

PMID- 18339538
TI  - Chromatin state maps: new technologies, new insights.
AB  - Recent years have seen unprecedented characterization of mammalian chromatin
      thanks to advances in chromatin assays, antibody development, and genomics.
      Genome-wide maps of chromatin state can now be readily acquired using microarrays
      or next-generation sequencing technologies. These datasets reveal local and long
      range chromatin patterns that offer insight into the locations and functions of
      underlying regulatory elements and genes. These patterns are dynamic across
      developmental stages and lineages. Global studies of chromatin in embryonic stem
      cells have led to intriguing hypotheses regarding Polycomb/trithorax and RNA
      polymerase roles in 'poising' transcription. Chromatin state maps thus provide a
      rich resource for understanding chromatin at a 'systems level', and a starting
      point for mechanistic studies aimed at defining epigenetic controls that underlie
      development.

PMID- 18339539
TI  - The emerging field of dynamic lysine methylation of non-histone proteins.
AB  - Post-translational modifications (PTMs) regulate protein structure and function.
      Lysine methylation abundantly decorates histone proteins and has recently been
      detected on non-histone proteins. In particular, the tumor suppressor and
      transcription factor p53 has provided a model for lysine methylation on a non
      histone protein. As found for histones, lysine methylation is dynamic and can be
      reversed by demethylation. Lysine methylation regulates function via several
      distinct mechanisms. Methyl lysine provides docking sites for binding of effector
      proteins. Methylation can serve to inhibit alternate PTMs on the same lysine
      residue. In addition, lysine can be monomethylated, dimethylated, or
      trimethylated, and these levels of methylation correlate with distinct genomic
      locations and functions. Taking into account combinatorial activity with numerous
      other PTMs, lysine methylation provides enormous functional diversity and
      regulatory complexity.

PMID- 18339540
TI  - Utilization of genomic signatures to direct use of primary chemotherapy.
AB  - The success of treatment of cancer patients depends on matching the most
      effective therapeutic regimen with the characteristics of the individual patient,
      balancing benefit against risk of adverse events. The primary challenge in
      achieving this goal is the heterogeneity of the disease, recognizing that breast,
      lung, colon and other cancers are not single diseases but rather an array of
      disorders with distinct molecular mechanisms. Genomic analyses, and in particular
      gene expression profiling, has been shown to have the capacity to dissect this
      heterogeneity and afford opportunities to match therapies with the
      characteristics of the individual patient's tumor. Here we review the success in
      developing gene expression signatures that have the capability of predicting
      response to various commonly used and newly developing cancer therapeutics. We
      further discuss the challenges and the opportunities in utilizing these tools in
      present-day clinical practice.

PMID- 18339541
TI  - Epigenetic interactions between transposons and genes: lessons from plants.
AB  - Transposons replicate, increase in copy number and persist in nature by moving,
      but insertion into genes is generally mutagenic. There is thus a strong selection
      for transposons that can achieve a balance between their own replication and
      minimal damage to their host. Epigenetic regulation proves to be a widespread way
      to achieve this balance, quieting transposition on the one hand, yet reversible
      on the other. As our understanding of epigenetics improves, the subtleties and
      the scope of how transposons can affect gene expression, both directly and
      indirectly, are becoming clearer.

PMID- 18339542
TI  - ATP-dependent chromatin remodeling enzymes: two heads are not better, just
      different.
AB  - ATP-dependent chromatin remodeling complexes enable rapid rearrangements in
      chromatin structure in response to developmental cues. The ATPase subunits of
      remodeling complexes share homology with the helicase motifs of DExx box
      helicases. Recent single-molecule experiments indicate that, like helicases, many
      of these complexes use ATP to translocate on DNA. Despite sharing this
      fundamental property, two key classes of remodeling complexes, the ISWI class and
      the SWI/SNF class, generate distinct remodeled products. SWI/SNF complexes
      generate nucleosomes with altered positions, nucleosomes with DNA loops and
      nucleosomes that are capable of exchanging histone dimers or octamers. In
      contrast, ISWI complexes generate nucleosomes with altered positions but in
      standard structures. Here, we draw analogies to monomeric and dimeric helicases
      and propose that ISWI and SWI/SNF complexes catalyze different outcomes in part
      because some ISWI complexes function as dimers while SWI/SNF complexes function
      as monomers.

PMID- 18339543
TI  - High-content analysis of cancer genome DNA alterations.
AB  - New technologies as well as concerted brute-force approaches have increased the
      content (number of genes) that can be characterized for genomic DNA alterations.
      Recent advances include the detection of activating point mutations in key kinase
      genes (BRAF, EGFR, and PIK3CA) in multiple cancer types: preliminary insight into
      the entire repertoire of genes that can be mutated in cancer; the discovery of
      new oncogenes by high-resolution profiling of DNA copy number alterations; and
      the bioinformatic-driven discovery of oncogenic gene fusions. High-content
      promoter methylation detection systems have been used to discover additional
      methylated genes and have provided evidence for a stem cell origin for certain
      tumors. Some of these advances have had significant impact on the development and
      clinical testing of new therapeutics.

PMID- 18339544
TI  - Leech locomotion: swimming, crawling, and decisions.
AB  - Research on the neuronal control of locomotion in leeches spans almost four
      decades. Recent advances reviewed here include discoveries that: (1) interactions
      between multiple hormones modulate initiation of swimming; (2) stretch receptors
      associated with longitudinal muscles interact with the central oscillator circuit
      via electrical junctions; (3) intersegmental interactions, according to
      theoretical analyses, must be relatively weak compared to oscillator interactions
      within ganglia; and (4) multiple interacting neurons control the expression of
      alternative modes of locomotion. The innovative techniques that facilitated these
      advances include optical recording of membrane potential changes, simultaneous
      intracellular injection of high and low molecular weight fluorescent dyes, and
      detailed modeling via an input-output systems engineering approach.

PMID- 18339545
TI  - Neurobiology of behaviour.

PMID- 18339546
TI  - Oscillatory interactions between sensorimotor cortex and the periphery.
AB  - Field potential recordings from motor cortex show oscillations in the beta-band
      (approximately 20 Hz), which are coherent with similar oscillations in the
      activity of contralateral contracting muscles. Recent findings have revised
      concepts of how this activity might be generated in the cortex, suggesting it
      could achieve useful computation. Other evidence shows that these oscillations
      engage not just motor structures, but also return from muscle to the central
      nervous system via feedback afferent pathways. Somatosensory cortex has strong
      beta-band oscillations, which are synchronised with those in motor cortex,
      allowing oscillatory sensory reafference to be interpreted in the context of the
      oscillatory motor command which produced it.

PMID- 18339547
TI  - Uniquely insidious: Yersinia pestis biofilms.
AB  - Bubonic plague, one of history's deadliest infections, is transmitted by fleas
      infected with Yersinia pestis. The bacteria can starve fleas by blocking their
      digestive tracts, which stimulates the insects to bite repeatedly and thereby
      infect new hosts. Direct examination of infected fleas, aided by in vitro studies
      and experiments with the nematode Caenorhabditis elegans, have established that
      Y. pestis forms a biofilm in the insect. The extracellular matrix of the biofilm
      seems to contain a homopolymer of N-acetyl-d-glucosamine, which is a constituent
      of many bacterial biofilms. A regulatory mechanism involved in Y. pestis biofilm
      formation, cyclic-di-GMP signaling, is also widespread in bacteria; yet only Y.
      pestis forms biofilms in fleas. Here, the historical background of bubonic plague
      is briefly described and recent studies investigating the mechanisms by which
      these unique and deadly biofilms are formed are discussed.

PMID- 18339548
TI  - Methodology for digital radiography simulation using the Monte Carlo code MCNPX
      for industrial applications.
AB  - This work presents a methodology for digital radiography simulation for
      industrial applications using the MCNPX radiography tally. In order to perform
      the simulation, the energy-dependent response of a BaFBr imaging plate detector
      was modeled and introduced in the MCNPX radiography tally input. In addition, a
      post-processing program was used to convert the MCNPX radiography tally output
      into 16-bit digital images. Simulated and experimental images of a steel pipe
      containing corrosion alveoli and stress corrosion cracking were compared, and the
      results showed good agreement between both images.

PMID- 18339549
TI  - An inter-laboratory comparison of low-level measurements in ground-level aerosol
      monitoring.
AB  - After the nuclear reactor accident of Chernobyl, the "Integrated Measurement and
      Information System (IMIS) for Monitoring the Environmental Radioactivity and
      Detecting Emissions from Nuclear Plants was implemented in Germany. IMIS is a
      nationwide comprehensive measuring system which permanently monitors the
      radioactivity in all important environment media in the whole federal territory.
      At approximately 40 sites, the activity concentration of radioactive substances
      is measured in air and precipitations. At least 14 of them are responsible for
      trace monitoring of radionuclides in the air. The legal bases of IMIS prescribe
      regular inter-laboratory comparison analyses in cooperation with the Physikalisch
      Technische Bundesanstalt (PTB), with the use of reference materials prepared by
      the Federal Coordinating Laboratories. In order to fulfil this requirement in the
      field of trace survey measurements in ground-level air, the Federal Office for
      Radiation Protection ("Bundesamt fur Strahlenschutz", BfS) and the PTB have
      conducted a comparison with real, dust-loaded reference filters in 2005. The
      comparison was organized within the framework of a cooperation of trace survey
      stations from Austria, Germany and Switzerland. The paper describes the
      preparation of the real, dust-loaded reference filters, the procedure for spiking
      the filters with the activity standard solution containing (22)Na, (88)Y, (89)Sr,
      (90)Sr, (125)Sb, (133)Ba, (134)Cs, and (241)Am. Some results are discussed and
      conclusions are given.

PMID- 18339550
TI  - Determination of emission probabilities of gamma photons in the decay of (56)Co.
AB  - The emission probabilities of gamma photons in the decay of (56)Co were
      determined at Czech Metrology Institute (CMI) by means of an HPGe detector. This
      detector was calibrated experimentally and by MCNP-computation in the energy
      range from 40 to 2754keV for a point source geometry and source-to-detector
      distance of 25cm. Experimental and computed peak and total efficiencies were
      compared and calibration curves were determined. Full-peak efficiencies were
      calculated for all (56)Co gamma-ray energies, and were used to calculate the
      emission probabilities. A set of point sources was prepared from a (56)Co
      solution. The solution was standardized using the 4pibeta-gamma coincidence
      method, and an ampoule was sent to international reference system for activity
      measurement of gamma-ray emitting radionuclides (SIR). Each point source was
      measured with the HPGe detector at a source-to-detector distance of 25cm.
      Coincidence emission probabilities of all the gamma photons were calculated and
      used to determine the summing correction factors.

PMID- 18339551
TI  - Precise tests of internal-conversion theory.
AB  - Using the 165.9-keV M1 transition in (139)La as a calibrant, we have determined
      the K-shell internal conversion coefficients (ICCs) for the 127.5-keV E3
      transition in (134)Cs and the 661.7-keV M4 transition in (137)Ba to 0.6%
      precision. Unlike previous less-precise measurements of these ICCs, which
      differed significantly from calculated values, our results agree well with
      calculations that include the atomic K-shell vacancy and disagree with those that
      exclude it. These results, which are consistent with what we also found for
      (193)Ir, confirm our earlier conclusions but for different energies,
      multipolarities and atomic numbers.

PMID- 18339552
TI  - The efficiency variation method for 4pibeta-gamma coincidence counting by ink-jet
      printing.
AB  - In order to vary the counting efficiencies in the 4pibeta-gamma coincidence
      extrapolation technique, a radioactive source was coated directly with varying
      amounts of an electrical conducting pigment using an ink-jet printer. This method
      can be used to efficiently prepare the multiple sources needed to generate
      efficiency extrapolation curves, and was successfully applied to the
      standardization of a (54)Mn source.

PMID- 18339553
TI  - Preventing strategy of multidrug-resistant Acinetobacter baumanii susceptible
      only to colistin in cardiac surgical intensive care units.
AB  - OBJECTIVE: The study aimed to determine the incidence and mortality of multidrug
      resistant Acinetobacter baumannii in cardiac surgery, to elucidate the
      effectiveness of colistin treatment and to identify if the additional measures to
      the recommended procedures were able to control the dissemination of the
      pathogen. METHODS: A prospective observational cohort was conducted among cardiac
      surgical patients from 1 September 2005 to 31 December 2006. We reviewed the
      prophylactic measures of the surgical intensive care unit and implemented a two
      scale multiple program. Scale I included classical infection control measures,
      while Scale II referred to the geographic isolation of multidrug-resistant
      Acinetobacter baumannii patients and environmental intense surveillance. RESULTS:
      Among 151 out of 1935 infected patients 20 were colonized and infected by strains
      of multidrug-resistant A. baumannii susceptible only to colistin. Seventeen
      patients presented respiratory tract infection, one patient suffered deep
      surgical site infection and two patients catheter related infection. Transmission
      of the pathogen occurred via two patients transferred from two other
      institutions. They were all treated with colistin. Cure or clinical improvement
      was observed only in four patients (20%). Scale I measures were implemented for
      the whole 16-month period while scale II for two separate periods of 3 weeks.
      Environmental specimens (n>350) proved negative. CONCLUSIONS: The increasing
      prevalence of multidrug-resistant A. baumannii in surgical intensive care unit
      patients creates demand on strict screening and contact precautions. Following
      this infection control strategy we were able to achieve intermittent eradication
      of the pathogen during a 16-month period with continuous function of the
      intensive care unit. Despite the significant in vitro activity of colistin
      against multidrug-resistant Acinetobacter baumannii the results were
      discouraging.

PMID- 18339554
TI  - Post-transplant diabetes mellitus in lung transplant recipients: incidence and
      risk factors.
AB  - OBJECTIVE: Post-transplant diabetes mellitus (PTDM) is a common and potentially
      serious complication after solid organ transplantation. There are only a few
      data, however, about the incidence of DM in patients undergoing lung
      transplantation. PATIENTS AND METHODS: The medical records of 119 consecutive
      patients who underwent lung transplantation from 1998 to September 2004 were
      reviewed. Patients were divided in three groups according to their diabetes
      status, including pre-transplant DM, the PTDM group and those without DM. Patient
      records and all laboratory data were reviewed and the clinical course of diabetes
      was monitored. All recipients were treated with tacrolimus based regimen.
      RESULTS: Mean follow-up for all patients was 25+/-10. Twenty-three patients had
      DM in the pre-lung transplantation (LTX) DM group. PTDM developed in 34 of the
      remaining 96 patients (35.4%) with an incidence of 20%, 23% after 6 months and 12
      months post-transplant. No significant difference was noted between 12 and 24
      months post-LTX. The patients who developed DM were older (57+/-15 vs 53+/-13
      years, p=0.009), had increased BMI (26+/-5 vs 24+/-4, p=0.0001), shorter time
      from diagnosis to LTX (21+/-13 vs 28+/-18 months, p=0.007) more cytomegalovirus
      infection and more acute rejection and hyperglycemia in the first month after
      LTX. Four patients died in the PTDM group compared to nine patients in the no-DM
      group (12% vs 14%; p=0.72). CONCLUSIONS: Post-transplant diabetes is a common
      complication in lung transplant patients receiving tacrolimus-based
      immunosuppression. The risk for developing PTDM is greatest among older
      recipients, those obese, and among recipients with more rejections episodes.

PMID- 18339556
TI  - Long-term results of redo gastro-esophageal reflux disease surgery.
AB  - OBJECTIVE: To review the long-term results of redo gastro-esophageal reflux
      disease (GERD) surgery with special emphasis on residual acid-suppressing
      medications, pH monitoring results, and quality of life. METHODS: Retrospective
      analysis of 52 patients (24 males) who underwent redo GERD surgery between 1986
      and 2006 through a transthoracic (n=14), or a transabdominal (n=38) approach.
      Indications were recurrent GERD in 41 patients, and complication of the initial
      surgery in 11. Quality of life was evaluated by telephone enquiry using a
      validated French questionnaire (reflux quality score, RQS). RESULTS:
      Postoperative complications occurred in 18 patients (35%), resulting in one death
      (2%). Reoperation was required in seven patients. At 1 year, 26 patients (51%)
      had 24h pH monitoring, among whom 2 (8%) were proved to have recurrence of GERD.
      RQS values were calculated in 38 patients with a mean follow-up of 113 months.
      Fifty percent of this subgroup had a RQS value beyond 26/32, indicating an
      excellent quality of life. Among these 38 patients, 20 (53%) had acid-suppressing
      medications whatever their RQS values. Patients who underwent transthoracic GERD
      surgery had the highest RQS values (p=0.02), a lower rate of complications
      (p=0.06) and a lower rate of reoperation (p=0.04). CONCLUSION: Our experience
      confirms that selection of candidates for redo GERD surgery is a challenging
      issue. A transthoracic approach seems to produce better results and lower rates
      of complications.

PMID- 18339557
TI  - The future of drug-eluting stents.
AB  - This review aims to provide a glimpse into the future of drug-eluting stents
      (DES). Since their arrival in 2002, DES have transformed the practice of
      interventional cardiology by drastically reducing restenosis and the need for
      repeat revascularization. However, data about the potentially fatal long-term
      risk of stent thrombosis have spurred on research and development to improve upon
      the first generation of devices. The initial commercially available DES used a
      stainless steel platform coated with a permanent polymer to provide controlled
      release of the anti-restenotic drug. The platform, polymer and drug are all
      targets for improvement. More advanced metallic and fully biodegradable stent
      platforms are currently under investigation. The permanent polymer coating, a
      likely contributor adverse events, is being superseded by biocompatible and
      bioabsorbable alternatives. New drugs and drug combinations are also a research
      goal, as interventional cardiologists and the industry strive towards safer anti
      restenotic DES.

PMID- 18339558
TI  - Effect of protonation and deprotonation on the gas-phase reactivity of
      fluorinated 1,2,4-triazines.
AB  - Positive and negative electrospray mass spectrometry (MS), in-time and in-space
      MS(n) experiments, high-resolution and accurate mass measurements obtained with
      an Orbitrap, together with density functional theory calculations have been used
      to study the gas-phase ion chemistry of a series of fluorinated 1,2,4-triazines.
      As a result of low-energy collision-induced dissociations, occurring in an ion
      trap and in a triple quadrupole, their protonated and deprotonated molecules show
      interesting features depending on the nature and structure of the precursor ions.
      The occurrence of elimination/hydration reactions produced by positive ions in
      the ion trap is noteworthy. Decompositions of deprotonated molecules, initiated
      by elimination of a hydroxyl radical from [M-H](-), are dominated by radical
      anions. Theoretical calculations have allowed us to obtain information on atom
      sites involved in the protonation and deprotonation reactions.

PMID- 18339559
TI  - Spatio-temporal characteristics of low-frequency BOLD signal fluctuations in
      isoflurane-anesthetized rat brain.
AB  - We studied the spatio-temporal characteristics of the resting state low-frequency
      fluctuations in fMRI-BOLD signal in isoflurane-anesthetized rats. fMRI-BOLD
      measurements at 9.4 T were made during normal and exsanguinated condition
      previously known to alter cerebral blood flow (CBF) fluctuations in anesthetized
      rats. fMRI signal time series were low pass filtered and studied by spectral
      analysis. During normal conditions, baseline mean arterial pressure (MAP) was
      110+/-10 mm Hg and low-frequency fluctuations in BOLD signal were observed in the
      frequency range of 0.01 to 0.125 Hz. Following blood withdrawal (exsanguination),
      MAP decreased to 68+/-7 mm Hg, resulting in an increase in the amplitude of the
      low-frequency fluctuations in BOLD signal time series and an increase in power at
      several frequencies between 0.01 and 0.125 Hz. Spatially, the BOLD fluctuations
      were confined to the cortex and thalamus spanning both hemispheres with sparse
      presence in the caudate putamen and hippocampus during both normal and
      exsanguinated states. Spatial distribution of the low-frequency fluctuations in
      BOLD signal, from cross-correlation analysis, indicates substantial inter
      hemispheric synchrony similar to that observed in the conscious human brain. The
      behavior of the resting state BOLD signal fluctuations similar to CBF
      fluctuations during exsanguination indicates a myogenic dependence. Also, a high
      inter-hemispheric synchrony combined with different phase characteristics of the
      low-frequency BOLD fluctuations particularly in the hippocampus relative to the
      cortex emphasizes distinct functional networks.

PMID- 18339560
TI  - Analysis of laminar activity in normal and injured rat spinal cord by manganese
      enhanced MRI.
AB  - The present study provides an account of a sensitive and rapid experimental
      approach for MRI visualization and analysis of spinal cord (SC) laminar activity
      in normal and injured animals. This approach is based upon neuronal activity
      dependant manganese (Mn) uptake after focal SC injection of MnCl(2), and
      subsequent ex-vivo magnetic resonance imaging (MRI) of activated SC pathways. The
      method was designed as an alternative to time-intensive histochemical and
      behavioral approaches typically used for analysis of spinal cord injury (SCI) and
      our results provide both anatomical and functional insights. We show that ex vivo
      imaging can determine layer-specific activity over an extended region of the rat
      SC. In addition, we demonstrate that the Mn concentration profile along the SC
      axis accurately reflects the type of SC injury. The approach is flexible since
      MRI analysis can be done immediately after animal sacrifice, or alternatively
      several days later, without a loss of sensitivity. Moreover, the integrity and
      functional state of SC circuitry can be analyzed in less than 1 h whereas several
      days and weeks are necessary to perform classical histochemical and behavioral
      analysis. Thus our method can be used for precise assessment of the extent of
      dysfunction or change in SC disorders and may facilitate the screening of
      molecules with therapeutic potential after SC injury.

PMID- 18339561
TI  - A comparison of intra-articular hyaluronan injection accuracy rates between three
      approaches based on radiographic severity of knee osteoarthritis.
AB  - OBJECTIVE: To compare the accuracy rates of intra-articular hyaluronic acid (HA)
      injections for osteoarthritis (OA) of the knee between the modified Waddell
      approach (an anteromedial approach with manipulative ankle traction at 30 degrees
      of knee flexion), an anteromedial approach with the subjects seated (hereinafter
      the seated anteromedial approach) and a lateral patellar approach based on the
      Kellgren-Lawrence (K-L) radiographic grade (II, III and IV). DESIGNS: Fifty
      patients with knee OA received HA injections through the three approaches. The
      accuracy rates were confirmed with a single radiograph after injections of a
      mixture of radiographic contrast medium. RESULTS: In the K-L grade IV cases
      (n=11), the accuracy rates through the modified Waddell approach (11 out of 11,
      100%) were significantly higher than those through the seated anteromedial
      approach (six out of 11, 55%) and the lateral patellar approach (six out of 11,
      55%) (P=0.035). No significant differences were detected in the accuracy rates of
      the participants classified as grade II (n=21) or III (n=18) cases between the
      modified Waddell approach (86% and 78%, respectively), the seated anteromedial
      approach (71% and 56%, respectively) and the lateral patellar approach (86% and
      61%, respectively) (P>0.05). CONCLUSION: Although previous studies have been
      conducted on the accuracy of needle placement into the intra-articular space of
      the knee, no evaluations were performed with the results categorized by
      radiographic severity. This study highlighted the need for clinicians to change
      the approach employed for HA injections, according to the severity of knee OA.

PMID- 18339562
TI  - In vitro odontoblast-like cell differentiation of cranial neural crest cells
      induced by fibroblast growth factor 8 and dentin non-collagen proteins.
AB  - During tooth development, cranial neural crest (CNC) cells represent a population
      of pluripotent stem cells that give rise to various dental tissues. This study
      aimed to investigate whether CNC cells could differentiate into odontoblast-like
      cells by in vitro induction. CNC cells were isolated from explants of cranial
      neural tubes and cultured in serum-free Dulbecco's modified Eagle's medium
      (DMEM)/F12 medium which contained fibroblast growth factor 8 (FGF8) and dentin
      non-collagen proteins (DNCP). The initiation of controlled differentiation was
      determined using histological assays, and the expression of specific gene
      phenotypes was detected using immunocytochemical staining and reverse
      transcription--polymerase chain reaction (RT--PCR). The first branchial arch
      phenotype of the CNC cells demonstrated negative Hoxa2 expression and positive
      vimentin expression in the presence of 100 ng/ml FGF8. Following DNCP induction,
      the CNC cells became bipolar, demonstrated high alkaline phosphatase (ALP)
      activity, and formed mineralized nodules. In addition, the expression of DSPP,
      DMP1, and collagen type I confirmed the odontoblast phenotype. The results
      indicate that the tissue-specific cellular differentiation (odontoblast-like
      cells) of early-stage embryonic-derived cells (such as CNC cells) can be induced
      by adult extracellular matrix proteins (such as DNCP). CNC cells may be used as a
      valuable cell model for research on dental tissue differentiation and
      regeneration.

PMID- 18339563
TI  - Characterization of Fusarium graminearum Mes1 reveals roles in cell-surface
      organization and virulence.
AB  - The surfaces of fungal hyphae are mosaics of carbohydrates and cell-surface
      proteins. Presently, very little is known about the role of these proteins and
      their organization at the cell surface. Here, we characterize two Fusarium
      graminearum genes implicated in cell-surface organization, mes1 (FGSG_06680) and
      pls1 (FGSG_08695). Mes1 is a homologue of mesA, which is required for the
      formation of stable polarity axes in Aspergillus nidulans. Pls1 encodes a
      tetraspanin, which belongs to a class of proteins that have been shown to
      aggregate in membrane rafts along with integrins and other signaling proteins.
      Our results indicate that Pls1 is dispensable for saprophytic growth and wheat
      head infection by F. graminearum (a pathogen that does not form appressoria).
      However, deletion of mes1 reduces sexual and asexual reproduction, severely
      perturbs the shape of macroconidia and hyphae, alters the pattern of cell wall
      deposition and the organization of sterol-rich rafts, and attenuates virulence on
      wheat heads. Our results provide a basis for identifying determinants of fungal
      virulence that may localize to specialized domains at the cell surface.

PMID- 18339564
TI  - Progeria caused by a rare LMNA mutation p.S143F associated with mild myopathy and
      atrial fibrillation.
AB  - We present a 6-year-old girl with premature aging associated with mild myopathy,
      displaying muscle weakness, joint contractures and hyporeflexia. Genetic analysis
      revealed rare heterozygous point mutation in lamin A/C gene, g.428C>T.
      Cardiological evaluation showed atrial fibrillation, but we did not find signs of
      coronary heart disease, which is life-threatening cardiovascular complication in
      progeria. Electron microscopy of the muscle revealed abnormalities in nuclear
      architecture, i.e. blebbing, thick lamina and peripheral distribution of
      heterochromatin. As some diagnostic criteria characteristic for classic progeria
      are not fulfilled, this case could be regarded as atypical progeria associated
      with myopathy and atrial fibrillation. To our knowledge, this is the second case
      of such association described in the literature.

PMID- 18339565
TI  - Modeling of asthma, COPD and cystic fibrosis in sheep.
AB  - Sheep naturally allergic to Ascaris suum antigen have been used to study the
      pathophysiology of asthma and more recently allergic rhinitis, chronic
      obstructive pulmonary disease (COPD) and cystic fibrosis. The utility of the
      model as it relates to the study of these diseases is discussed.

PMID- 18339566
TI  - The non-human primate as a model for studying COPD and asthma.
AB  - This review evaluates the current status of information regarding the nonhuman
      primate as an experimental model for defining mechanisms of chronic airways
      disease in humans, using the concept of the epithelial-mesenchymal trophic unit
      (EMTU) as a basis for comparison with other laboratory species. All of the
      cellular and acellular compartments within the walls of tracheobronchial airways
      which interact as the EMTU are present throughout the airway tree in human and
      nonhuman primates. The epithelial compartment contains mucous goblet and basal
      cells in the surface epithelium and submucosal glands within the wall. The
      interstitial compartment of primates has a prominent subepithelial basement
      membrane zone (BMZ) with an attenuated fibroblast sheath and cartilage throughout
      the tree. In primates, there is an extensive transition zone between distal
      conducting airways and lung parenchyma composed of numerous generations of
      respiratory bronchioles. None of these features are characteristic of
      intrapulmonary airways in rodents, whose airways do share ciliated cells, smooth
      muscle cells, nerve networks, vasculature and inflammatory cell populations with
      primates. While the numbers of intrapulmonary airway branches are similar for
      most mammals, branching patterns, which dictate distribution of inhaled
      materials, are more uniform (dichotomous) in primates and less so (monopodial) in
      rodents. Development of tracheobronchial airways (both differentiation of the
      EMTU and overall growth) occurs over an extensive postnatal period (months to
      years) in primates and a comparably shorter time period (2-3 weeks) in rodents.
      As with allergic airways disease in humans, experimental exposure of nonhuman
      primates to a known human allergen, house dust mite, produces extensive
      remodeling of all compartments of the EMTU: mucous goblet cell hyperplasia,
      epithelial sloughing, basement membrane zone (BMZ) thickening and reorganization,
      altered attenuated fibroblast function, subepithelial fibrosis and smooth muscle
      thickening. Experimental allergic airways disease in nonhuman primates also
      shares other features with asthmatic humans: positive skin test to allergen;
      allergen-specific circulating IgE; airway hyper responsiveness to allergen,
      histamine and methacholine; increased eosinophils, IGE positive cells and mucins
      in airway exudate; and migratory leukocyte accumulations in the airway wall and
      lumen. Experimental exposure of nonhuman primates to reactive gases, such as
      ozone, produces the chronic respiratory bronchiolitis and other airway
      alterations associated with restricted airflow and chronic respiratory
      bronchiolitis characteristic of COPD in young smokers. We conclude that nonhuman
      primate models are appropriate for defining mechanisms as they relate to allergic
      airways disease and COPD in humans.

PMID- 18339567
TI  - Presumed primary immune-mediated thrombocytopenia in four cats.
AB  - Feline primary immune-mediated thrombocytopenia (pIMT) is a rare hematological
      disorder. Platelet-bound antibody assays for cats have variable specificity and
      sensitivity and are not widely available. Diagnosis of pIMT is made on the basis
      of exclusion of other identifiable causes of thrombocytopenia and the response to
      immunosuppressive therapy. This report describes four cats with severe
      thrombocytopenia and no detectable underlying disease. One cat was euthanased
      because of pulmonary hemorrhage, while the other cats had frequent relapses, two
      of these cats developed diabetes mellitus due to long-term corticosteroid
      therapy. In these cats IMT had a chronic course and responded poorly to therapy
      with prednisolone. Alternative immunomodulatory drugs may be considered in the
      treatment of feline IMT.

PMID- 18339568
TI  - Schistosoma reflexum in a cat: insights into aetiopathogenesis.
AB  - A foetal cat exhibiting multiple congenital malformations and meeting the
      criteria for being considered as a case of true schistosoma reflexum (SR) is
      described. SR in animals is briefly compared with relatively similar malformation
      entities in humans. Murine gene mutations producing severe ventral body wall
      defects associated with anomalies of internal organs and other structures are
      briefly reviewed. New insights into aetiopathogenic mechanisms possibly
      implicated in the development of SR are suggested. This is probably the first
      case of true SR reported in the cat.

PMID- 18339569
TI  - Correlation between radioactivity induced inside the treatment room and the
      undesirable thermal/resonance neutron radiation produced by linac.
AB  - High-energy therapeutic beams used in the radiotherapy induce photonuclear and
      electronuclear reactions which are accompanied by generation of undesirable
      radioisotopes and neutrons inside the treatment room. These neutrons at thermal
      and resonance energies induce nuclear reactions through the whole accelerator
      bunker. In consequence various radioisotopes emitting high-energy photons appear.
      In this paper the correlation between radioactivity induced inside the treatment
      room and the undesirable thermal and resonance neutron radiation generated by the
      therapeutic accelerator X-rays was studied. The thermal and resonance neutron
      fluence determined in chosen places inside the bunkers was 1.0x10(5)-3.4x10(5)cm(
      2)Gy(-1) and 1.0x10(5)-1.6x10(6)cm(-2)Gy(-1) at thermal energies (<0.1eV) and
      3.9x10(4)-1.3x10(5)cm(-2)Gy(-1) and 1.0x10(5)-1.1x10(6)cm(-2)Gy(-1) at epithermal
      energies (0.1eV-10keV), for the 15MV and 20MV beams, respectively. The gamma
      energy spectra measured inside the accelerator bunker depended on the neutron
      radiation level. The net count rates of the gamma peaks from the decays of the
      excited state (56)Fe* and (28)Si*, the result of the simple capture of the
      neutron, for the 20MV beam were almost one order of magnitude greater than those
      for the 15MV beam. Moreover, it turned out that the activation of the wedge - the
      main accelerator accessory was caused by neutrons.

PMID- 18339570
TI  - [Nasopharyngeal angiofibroma with intracranial extension: situating the
      chemotherapy-radiotherapy association].
AB  - Nasopharyngeal angiofibroma is a locally aggressive, although histologically
      benign, vascular neoplasm. This neoplasm accounts for 0.05% of head and neck
      tumours and affects almost exclusively male adolescents. Surgery is considered as
      the primary treatment of nasopharyngeal angiofibroma. Other treatment modalities
      such as radiotherapy and chemotherapy are still recommended for intracranial
      extension involving the cavernous sinus or the internal carotid artery. We report
      a rare case of nasopharyngeal angiofibroma, further complicated with a Kennedy
      syndrome in a 34 year-old women. The treatment consisted in a chemotherapy
      (adriamycine, decarbazine) followed by radiotherapy. We discuss the relevance and
      outcome of the association chemotherapy-radiotherapy in the treatment of
      nasopharyngeal angiofibromas with a consistent intracranial extension (stage III
      B of Arch Otolaryngol Head Neck Surg 122 (2003) 122-129).

PMID- 18339571
TI  - Natural death of adult Onchocerca volvulus and filaricidal effects of doxycycline
      induce local FOXP3+/CD4+ regulatory T cells and granzyme expression.
AB  - Immunosuppression in human filarial disease involves regulatory T cells. We
      hypothesized that natural or worm antigen-induced FOXP3 regulatory T cells could
      be involved locally, suppressing effector cells via granzymes. Natural and
      treatment-induced death of worms implies enhanced exposure to worm antigens.
      Therefore, we examined FOXP3+T cells and granzyme expression in onchocercomas
      harbouring adult Onchocerca volvulus worms, with respect to worm viability,
      productivity, the patient's immune status and filaricidal treatment. The
      immunohistological analysis revealed that dead adult worms were strongly
      associated with FOXP3+T cells in generalized hyporeactive onchocerciasis. FOXP3+
      cells hardly expressed granzymes, but cell contacts with granzyme A+ or B+ cells
      were frequent. While suramin directly kills most adult worms within 6 months, the
      Wolbachia depleting antibiotic doxycycline indirectly causes adult worm
      degeneration within 18 months. Contrary to suramin, depletion of Th1-driving
      endobacteria most strongly promoted FOXP3+T cells and granzyme-expressing cells.
      In hyperreactive patients, FOXP3+ cells were less frequent. This is the first
      demonstration of local FOXP3+Treg cells in human filariasis and their induction
      by natural worm death and anti-parasitic treatment. We newly report granzyme
      responses to helminths and their association with immunosuppression. FOXP3+Treg
      and granzyme+ cells might locally suppress defence against newly acquired worms.

PMID- 18339572
TI  - [Screening for Y chromosome microdeletions in assisted reproductive techniques].
AB  - In case of infertility due to azoospermia, clinical, sonographical and biological
      examinations suggest obstructive or non obstructive causes. In cases of non
      obstructive azoospermia, genomic microdeletions must be determined particularly
      in the Y chromosome long arm, as well as autosomal abnormality. A constitutional
      karyotype must also be done. The so-called Y AZFa, AZFb and AZFc zones could be
      partially or totally absent. Genotype is mostly correlated with histology. Thus,
      when large AZFa and AZFb microdeletions are detected there is theoretically no
      chance to find testicular spermatozoa. If only AZFc microdeletions are present,
      testicular biopsy is possible with a good chance of mature spermatozoa retrieval
      before microinjection, and AZFc microdeletions are also often present (10%) in
      cases of severe oligospermia. Couples must be informed of genomic deletions and a
      genetic counseling is essential to explain the potential childhood risks after
      assisted reproductive techniques. This problem has been discussed by the French
      "High Authority of Health". It recommends determination of these Y microdeletions
      when oligozoospermia is severe (lower than one million spermatozoa per
      milliliter).

PMID- 18339573
TI  - Topiramate in managing impulse control disorders in Parkinson's disease.

PMID- 18339574
TI  - The integrated continence system: a manual therapy approach to the treatment of
      stress urinary incontinence.
AB  - Stress urinary incontinence (SUI) constitutes a large-scale public health
      concern. The integrated continence system (ICS) developed by the authors is an
      evidence-based model that demonstrates how urinary incontinence is maintained
      through the interaction of three structural systems (intrinsic urethral closure,
      urethral support and lumbopelvic stability) and three modifiable factors (motor
      control, musculoskeletal and behavioural). The purpose of the ICS is first, to
      demonstrate the important role that manual physiotherapists can play in the
      treatment of SUI and second, to guide clinical practice decisions in order to
      improve clinical outcomes among women with SUI.

PMID- 18339575
TI  - The role of proteases in pathologies of the synovial joint.
AB  - Synovial (diarthrodial) joints are employed within the body to provide skeletal
      mobility and have a characteristic structure adapted to provide a smooth almost
      frictionless surface for articulation. Pathologies of the synovial joint are an
      important cause of patient morbidity and can affect each of the constituent
      tissues. A common feature of these pathologies is degenerative changes in the
      structure of the tissue which is mediated, at least in part, by proteolytic
      activity. Most tissues of the synovial joint are composed primarily of
      extracellular matrix and key pathological roles in the degeneration of this
      matrix are performed by metalloproteinases such as matrix metallproteinases
      (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs
      (ADAMTS). However, other proteases such as cathepsin K are likely to play an
      important role, especially in bone turnover. In addition to the cleavage of
      structural proteins, proteolytic activities are employed to regulate the activity
      of other proteases, growth factors, cytokines and other inflammatory mediators.
      Proteases combine to form complex regulatory networks, the correct functioning of
      which is required for tissue homeostasis and the imbalance of which may be a
      feature of pathology. A precise understanding of the proteases involved in these
      networks is required for a true understanding of the associated pathology.

PMID- 18339576
TI  - The soluble transforming growth factor-beta receptor: advantages and
      applications.
AB  - Transforming growth factor-beta (TGF-beta) is a cytokine that plays a pivotal
      role in growth, differentiation, development, immune response and wound healing.
      TGF-beta is upregulated following wound infliction and inflammation, and plays an
      important role in the production of extracellular matrix proteins that contribute
      to tissue repair. However, in some diseases, TGF-beta dysregulation can lead to
      tumor formation, organ fibrosis and the disruption of organ function. A number of
      molecules have been designed to counteract the effects of TGF-beta, including
      anti-TGF-beta monoclonal antibodies and various small molecules. Here we discuss
      the design, use and advantages of the highly specific TGF-beta binding molecule,
      the soluble human TGF-beta receptor (sTbetaR.Fc) as a TGF-beta sequestering
      agent.

PMID- 18339577
TI  - Effect of doping an organic molecule ligand on TGS single crystals.
AB  - Good quality single crystals of thiourea-doped triglycinesulphate (TuTGS) a new
      semiorganic nonlinear optical (NLO) crystal has been successfully grown from
      aqueous solution by slow evaporation method. The solubilities under various
      solvents in different proportions have been studied. The structural
      characterization of the grown crystals was carried out by X-ray diffraction. The
      grown crystals were subjected to FTIR and Raman analyses for vibrational
      assignments. The optical absorption coefficient alpha was analysed and
      interpreted to be allowed in the direct transition. The values of allowed direct
      energy gap (Eg) for undoped and doped crystals were calculated. It was found that
      Eg values were decreased with organic molecule doping. The powder technique of
      Kurtz and Perry confirm the NLO property of the grown crystal.

PMID- 18339578
TI  - Electron paramagnetic resonance and optical absorption spectral studies on
      covellite mineral.
AB  - A covellite mineral sample from Coquimbo region, Chile is used in the present
      study. An electron paramagnetic resonance (EPR) study on powdered sample confirms
      the presence of Mn(II) and Cu(II). Optical absorption spectrum indicates that
      Fe(II) and Cu(II) impurities are present in octahedral structure. Bands in the
      near-infrared from 7,000 to 5,000 cm(-1) result from the overtones of the first
      fundamental OH-stretching modes.

PMID- 18339579
TI  - High prevalence of Human Herpes Virus 8 (HHV-8) in patients with Warthin's tumors
      of the salivary gland.
AB  - BACKGROUND: Warthin's tumor is a common benign neoplasm of the salivary gland.
      Human Herpes Virus 8 (HHV-8) is the etiologic agent for all forms of Kaposi's
      sarcoma (KS), and HHV-8 DNA is present in saliva, suggesting that non-sexual
      transmission is associated with latent infection of the salivary gland.
      OBJECTIVES: To provide insights into the HHV-8 cell tropism, the presence of HHV
      8 was investigated in a series of Warthin's tumors of the salivary gland and
      corresponding adjacent normal tissue. STUDY DESIGN: Forty-three patients with
      Warthin's tumors (cystadenolymphoma) were tested for the presence of HHV-8 DNA,
      and corresponding adjacent normal tissue samples were obtained from 15 patients.
      DNA was extracted from the paraffin-embedded tissues. A nested polymerase chain
      reaction (PCR) assay was applied, and the positive samples were confirmed by
      direct sequencing. RESULTS: HHV-8 DNA was detected in 19 out of 43 (44%) salivary
      gland tumor samples. Among the 15 cases with paired samples, 9 were HHV-8
      positive for both samples, 4 were HHV-8-negative for both samples while in two
      cases HHV-8 was detected only in the tumor specimens. CONCLUSIONS: HHV-8 is
      frequently detected in adenoid salivary neoplasms, suggesting a significant role
      of the virus in the etiopathogenesis of the disease. Larger studies are required
      to investigate the role of HHV-8 in the development or progression of Warthin's
      tumors.

PMID- 18339580
TI  - Prevalence and genotypes identification of human papillomavirus infection in a
      population of South Italy.
AB  - BACKGROUND: A limited number of human papillomavirus (HPV) types account for the
      majority of invasive cervical cancer cases. OBJECTIVES: To assess, in a southern
      Italian region, where HPV infection had not yet been investigated, the prevalence
      of type-specific HPV infection. STUDY DESIGN: Multiplex PCR was used to test
      cervical specimens from 871 asymptomatic women. RESULTS: The HPV infection rate
      was 23.1%, with the highest prevalence being observed in women aged 20-30 years
      (32.6%). Type 16 was the most frequent HPV type detected either in mono-infected
      (39.8%) or in multi-infected (46.3%) women. CONCLUSIONS: The HPV infection rate
      was higher than reported from other Italian areas. Our results further emphasise
      the importance of vaccinations to immunize females before they acquire HPV
      infection.

PMID- 18339581
TI  - Genomic DNA hypomethylation as a biomarker for bladder cancer susceptibility in
      the Spanish Bladder Cancer Study: a case-control study.
AB  - BACKGROUND: DNA hypomethylation has been suggested to cause genomic instability
      and increase cancer risk. We aimed to test the hypothesis that DNA
      hypomethylation is associated with increased risk of bladder cancer. METHODS: We
      measured cytosine methylation (5-mC) content in genomic DNA from blood cells from
      patients with bladder cancer enrolled in a large case-control study in Spain
      between Jan 1, 1998, and Dec 31, 2001. Cases were men and women with newly
      diagnosed and histologically confirmed urothelial carcinoma of the bladder.
      Controls were selected from patients admitted to the same hospital for diseases
      or conditions unrelated to smoking or other known risk factors for bladder
      cancer. Controls were individually matched to cases on age (within 5 years), sex,
      race, and area of hospital referral. 5-mC content was measured in leucocyte DNA
      by use of a combination of high-performance capillary electrophoresis, Hpa II
      digestion, and densitometry. Data on demographics, 34 polymorphisms in nine
      folate metabolism genes, and nutritional intake of six B vitamins (including
      folate), alcohol, and smoking were assessed as potential confounders. Relative 5
      mC content was expressed as a percentage (%5-mC) with respect to the total
      cytosine content (the sum of methylated and non-methylated cytosines). The
      primary endpoint was median %5-mC DNA content. FINDINGS: %5-mC was measured in
      leucocyte DNA from 775 cases and 397 controls. Median %5-mC DNA was significantly
      lower in cases (3.03% [IQR 2.17-3.56]) than in controls (3.19% [2.46-3.68],
      p=0.0002). All participants were subsequently categorised into quartiles by %5-mC
      content in controls. When the highest quartile of %5-mC content was used as the
      reference category (Q4), the following adjusted odds ratios (OR) and 95% CI were
      recorded for decreasing methylation quartiles: OR(Q3) 2.05 (95% CI 1.37-3.06);
      OR(Q2) 1.62 (1.07-2.44); and OR(Q1) 2.67 (1.77-4.03), p for trend <0.0001. The
      lowest cancer risk was noted in never smokers in the highest methylation quartile
      (never smokers in Q4). By comparison with never smokers in the highest quartile,
      current smokers in the lowest methylation quartile had the highest risk of
      bladder cancer (Q1: OR 25.51 [9.61-67.76], p for interaction 0.06). In analyses
      stratified by smoking, hypomethylation was a strong risk factor in never smokers
      (OR 6.39 [2.37-17.22]). Amount of methylation in controls were not associated
      with baseline characteristics, micronutrients, or selected genotypes in folate
      metabolism pathways. INTERPRETATION: For the first time, to our knowledge, we
      have shown in a large case-control study that leucocyte DNA hypomethylation is
      associated with increased risk of developing bladder cancer, and this association
      is independent of smoking and the other assessed risk factors. Amount of global
      methylation in genomic DNA could provide a useful biomarker of susceptibility to
      certain cancer types and further research is warranted.

PMID- 18339582
TI  - Macrolides as immunomodulatory medications for the therapy of chronic lung
      diseases.
AB  - Macrolide antibiotics have potent immunomodulatory activity. The spectrum of
      action of these antibiotics extends to regulation of leukocyte function and
      production of inflammatory mediators, control of mucus hypersecretion, resolution
      of inflammation, and modulation of host defense mechanisms. Macrolides are now
      being used or investigated to treat chronic lung inflammatory diseases, including
      diffuse panbronchiolitis (DPB), cystic fibrosis (CF), chronic obstructive
      pulmonary disease (COPD) and asthma. Intense research is ongoing to further
      elucidate the targets and mechanism/s of action of macrolides in eukaryotic
      cells. In this paper, we review recent findings on novel effects of macrolides on
      epithelial barrier function and resolution of inflammation, which may shed light
      on the mechanisms underlying the beneficial effects of macrolides in the clinic.

PMID- 18339583
TI  - Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle
      proliferation.
AB  - Uterine fibroids are the most common tumours presenting in women. The
      pathophysiology of fibroids is poorly understood, but disordered angiogenesis and
      altered smooth muscle cell proliferation are believed to play a role. In this
      review, current knowledge of both of these processes will be summarized.
      Differences between 'normal' adjacent myometrium and fibroid tumours within the
      same uterus are outlined. Exploiting these differences represents one of the best
      opportunities for the development of medical treatments that target fibroid
      tissue selectively.

PMID- 18339584
TI  - Preparation and characterization of insulin nanoparticles using chitosan and its
      quaternized derivatives.
AB  - Insulin (INS), like other peptides, has low therapeutic activity when
      administered orally due to degradation by proteolytic enzymes. Polymeric
      nanoparticles have been introduced as a useful carrier for peptide oral delivery,
      because they can protect these compounds from degradation. The objective of the
      present study is to develop an INS nanoparticulate system by using chitosan (CS),
      triethylchitosan (TEC), and dimethyl-ethylchitosan (DMEC, a new quaternized
      derivative of CS). INS-polymer nanoparticles were prepared by the polyelectrolyte
      complexation method. The physicochemical properties of the nanoparticles
      including particle size distribution, zeta potential, and polydispersity index
      were determined by using dynamic light scattering technique. Transmission
      electron microscopy was also used to observe the morphology of the nanoparticles.
      The amount of INS loaded into the nanoparticles was determined by measuring the
      association efficiency and also the content of INS in the nanoparticles. In vitro
      release studies showed a relatively small burst effect at the beginning and then
      a sustained release characteristic for 5 hours.

PMID- 18339585
TI  - Structural and functional changes in the membrane and membrane skeleton of red
      blood cells induced by peroxynitrite.
AB  - The changes in passive ion permeability of the red blood cell membrane after
      peroxynitrite action (3 microM-3 mM) have been studied by biophysical (using
      radioisotopes of rubidium, sodium and sulphur (sulphate)) and
      electrophysiological methods. The enhancement of passive membrane permeability to
      cations (potassium and sodium ions) and the inhibition of anion flux through the
      anion exchanger in peroxynitrite-treated red blood cells were revealed. In patch
      clamp experiments the whole-cell conductance after peroxynitrite (80 microM)
      treatment of red blood cells increased 3-3.5-fold with a shift in the reversal
      potential from -7.0+/-1.5 mV to -4.3+/-0.9 mV (n=7, p=0.005). The addition of
      cobalt and nickel ions to red blood cell suspensions before peroxynitrite
      treatment had no effect on the peroxynitrite-induced cation flux but zinc ions in
      the same condition decreased cation flux about 2-fold. Using atomic force
      microscopy methods we revealed an increase in red blood cell membrane stiffness
      and the membrane skeleton complexity after peroxynitrite action. We conclude that
      the peroxynitrite-induced water and ion imbalance and reorganization in membrane
      structure lead to crenation of red blood cells.

PMID- 18339586
TI  - Do all of the neurologic diseases in patients with DNA repair gene mutations
      result from the accumulation of DNA damage?
AB  - The classic model for neurodegeneration due to mutations in DNA repair genes
      holds that DNA damage accumulates in the absence of repair, resulting in the
      death of neurons. This model was originally put forth to explain the dramatic
      loss of neurons observed in patients with xeroderma pigmentosum neurologic
      disease, and is likely to be valid for other neurodegenerative diseases due to
      mutations in DNA repair genes. However, in trichiothiodystrophy (TTD), Aicardi
      Goutieres syndrome (AGS), and Cockayne syndrome (CS), abnormal myelin is the most
      prominent neuropathological feature. Myelin is synthesized by specific types of
      glial cells called oligodendrocytes. In this review, we focus on new studies that
      illustrate two disease mechanisms for myelin defects resulting from mutations in
      DNA repair genes, both of which are fundamentally different than the classic
      model described above. First, studies using the TTD mouse model indicate that
      TFIIH acts as a co-activator for thyroid hormone-dependent gene expression in the
      brain, and that a causative XPD mutation in TTD results in reduction of this co
      activator function and a dysregulation of myelin-related gene expression. Second,
      in AGS, which is caused by mutations in either TREX1 or RNASEH2, recent evidence
      indicates that failure to degrade nucleic acids produced during S-phase triggers
      activation of the innate immune system, resulting in myelin defects and
      calcification of the brain. Strikingly, both myelin defects and brain
      calcification are both prominent features of CS neurologic disease. The similar
      neuropathology in CS and AGS seems unlikely to be due to the loss of a common DNA
      repair function, and based on the evidence in the literature, we propose that
      vascular abnormalities may be part of the mechanism that is common to both
      diseases. In summary, while the classic DNA damage accumulation model is
      applicable to the neuronal death due to defective DNA repair, the myelination
      defects and brain calcification seem to be better explained by quite different
      mechanisms. We discuss the implications of these different disease mechanisms for
      the rational development of treatments and therapies.

PMID- 18339587
TI  - Size exclusion chromatography with evaporative light scattering detection: Method
      for the determination of polydimethylsiloxanes. II. Application of TSK-GEL H HR
      GMH HR -M column to determine and separate molecular weight of linear
      polydimethylsiloxanes.
AB  - Issues concerned with molecular weight distribution analysis of linear
      polydimethylsiloxanes have not been extensively investigated and mastered, yet.
      Current publications do not provide detailed research data on the evaluation of
      the polymerization degree of polydimethylsiloxanes (PDMS) present in variable
      matrices: e.g. pharmaceuticals, cosmetics, foodstuffs nor indicate molecular
      weights of the polymer used. However, the information on molecular weight, i.e.
      viscosity, is of primary importance as it directly affects PDMS toxicity,
      absorption and migration in the living organism. The vast majority of currently
      applied methods prove to be insufficiently specific for PDMS of a particular
      molecular weight and therefore alternative analytical methods have to be further
      researched. In this paper the results of determination of molecular weights in
      linear polydimethylsiloxanes, using size exclusion chromatography with the
      evaporative light scattering detector are described. The column calibration curve
      obtained from low-dispersion standard polystyrene of molecular weights ranging
      376-2,570,000 Da was used to determine PDMS molecular weights. Precision and
      accuracy of determination was obtained. For the mobile phase flow-rate of 0.3
      ml/min relative standard deviation RSD ranged to 0.45% and the accuracy of
      measurement amounted to -0.42%, whereas for flow-rate of 1.0 ml/min RSD ranged to
      0.38% and accuracy to +2.15%.

PMID- 18339588
TI  - Simultaneous quantification of four active schisandra lignans from a traditional
      Chinese medicine Schisandra chinensis(Wuweizi) in rat plasma using liquid
      chromatography/mass spectrometry.
AB  - A simple, rapid and sensitive method was developed for the simultaneous
      quantification of four active schisandra lignans (schisandrin, schisantherin A,
      deoxyshisandrin and gamma-schisandrin) from a traditional Chinese medicine
      Schisandra chinensis(Wuweizi) in rat plasma using a high-performance liquid
      chromatography system coupled to a positive ion electrospray mass spectrometric
      analysis. The plasma sample preparation was a simple deproteinization by the
      addition of three volumes of methanol followed by centrifugation. The analytes
      and internal standard (IS) bicyclol were separated on a Zorbax SB-C18 column (3.5
      microm, 2.1 mm x 100 mm) with mobile phase of methanol/water (70:30, v/v)
      containing 0.1% formic acid at a flow rate of 0.2 mL/min with an operating
      temperature of 25 degrees C. Detection was performed on a Trap XCT mass
      spectrometer equipped with an electrospray ionization (ESI) source operated in
      selected ion monitoring (SIM) mode. Positive ion ESI was used to form sodium
      adduct molecular ions at m/z 455 for schisandrin, m/z 559 for schisantherin A,
      m/z 439 for deoxyshisandrin, m/z 423 for gamma-schisandrin, and m/z 413 for the
      internal standard bicyclol. Linear detection responses were obtained for the four
      test compounds ranging from 0.010 to 2.0 microg/mL and the lower limits of
      quantitation (LLOQs) for four lignans were 0.010 microg/mL. The intra- and inter
      day precisions (R.S.D.%) were within 12.5% for all analytes, while the deviation
      of assay accuracies was within +/-13.0%. The average recoveries of analytes were
      greater than 80.0%. All analytes were proved to be stable during all sample
      storage, preparation and analytic procedures. The method was successfully applied
      to the pharmacokinetic study of the four lignans after oral administration of
      Schisandra chinensis extraction to rats.

PMID- 18339589
TI  - Quantitative analysis of 17 amino acids in the connective tissue of patients with
      pelvic organ prolapse using capillary electrophoresis-tandem mass spectrometry.
AB  - The simultaneous determination of 17 amino acids in connective tissue using
      capillary electrophoresis is described in this study. Separation was carried out
      on a fused silica capillary column (80 cm x 50 mm i.d.) with 1M formic acid as
      the running electrolyte. The detection was conducted on a mass spectrometer by
      selective reaction monitoring (SRM) mode via an electrospray ionization source.
      Tissue samples were prepared by reduction and acid hydrolysis to extract amino
      acids; over 84.3% recovery was seen for all compounds. The method allowed for
      sensitive, reproducible, and reliable quantification, and all 17 amino acids were
      separated using this method. Good linearity over the investigated concentration
      ranges was observed, with values of R higher than 0.993 for all the analytes.
      Precision and accuracy examined at three concentration levels ranged from 0.2% to
      19.5% and 84.1% to 120.0%, respectively. Matrix effects were also tested and
      ranged from -9.1% to 15.4%. The validated method was applied to the quantitation
      of 17 amino acids in pelvic connective tissue of pelvic organ prolapsed patients.
      Methionine, glutamine, and histidine were significantly higher in the
      experimental patients compared to the controls. This suggests that changes in the
      amino acid concentrations within the connective tissue could be a factor in the
      genesis of pelvic organ prolapse. Therefore, this method is potentially
      applicable for amino acid analysis in tissue, providing a more complete
      understanding of pelvic organ prolapse.

PMID- 18339590
TI  - Inhibitory effect of osthole on alcohol-induced fatty liver in mice.
AB  - BACKGROUND: Alcohol is a major cause of fatty liver, the disease is a spectrum
      that is initiated with steatosis, and without therapy it is apt to develop
      inflammation, necrosis, fibrosis and finally cirrhosis. There are currently no
      ideal pharmacological reagents that can prevent or reverse this disease. Osthole
      is an active constituent isolated from the fruit of Cnidium monnieri (L.) Cusson,
      a Chinese herbal medicine, which has been used in clinics for many years. It has
      many functions such as anti-inflammation, anti-osteoporosis and anti-tumor and so
      on, but there is no report about treatment of alcoholic fatty liver in mice. AIM:
      To examine the inhibitory effect of osthole on alcohol-induced fatty liver in
      mice and to investigate the potential mechanisms. METHODS: A mouse model with
      alcoholic fatty liver was induced by orally feeding 52% erguotou wine by gavage
      when they were simultaneously treated with osthole 10, 20, 40 mg/kg for 4 weeks.
      Whereafter, the lipids in serum and hepatic tissue, the levels of malondialdehyde
      (MDA), superoxide dismutase (SOD), reduced glutathione hormone (GSH), tumor
      necrosis factor-alpha (TNF-alpha) in hepatic tissue, hepatic weight coefficient
      and its histological evaluation were measured. RESULTS: After treatment with
      osthole, the levels of serum total cholesterol (TC), triglyceride (TG),
      coefficient of hepatic weight, and the hepatic tissue contents of TC and TG were
      significantly decreased, the levels of MDA and TNF-alpha in liver were also
      decreased, while the GSH in liver was increased. Importantly, the histological
      evaluation of liver specimens demonstrated that osthole dramatically decreased
      lipid accumulation. CONCLUSION: Osthole could inhibit alcohol-induced fatty liver
      in mice, and the mechanism might be associated with its anti-oxidation and
      suppression of TNF-alpha production.

PMID- 18339591
TI  - Prevalence of irritable bowel syndrome among undergraduates in Southeast China.
AB  - BACKGROUND: There is a wide range in reported prevalence of irritable bowel
      syndrome worldwide. From the data appeared recently in medical literatures in
      China, it seems that the incidence of irritable bowel syndrome in young adults is
      not dissimilar to the one in the Western countries. AIMS: To explore the
      prevalence and epidemiological variations of irritable bowel syndrome in an
      undergraduate student population in Southeast China on the basis of the Rome II
      and Rome III criteria. METHODS: All the undergraduate student participants were
      administered self-report diagnostic measures for irritable bowel syndrome.
      RESULTS: The sex-adjusted prevalence rate of irritable bowel syndrome was 4.7%
      (Rome II) and 10.4% (Rome III), respectively. When we combined irritable bowel
      syndrome mixed and irritable bowel syndrome unsubtyped in the Rome III subgroups
      into one group considering the counterpart in the Rome II subgroups was
      alternative irritable bowel syndrome, the agreement between the two ways to
      subdivide these 54 patients who were identified with irritable bowel syndrome by
      both the two criteria was 81%, with a kappa value of 0.67. By the Rome III
      criteria, we found a female predominance which was especially attributed to the
      subtypes of irritable bowel syndrome with constipation and unsubtyped.
      CONCLUSIONS: Our study suggests that, in young adults in Southeast China,
      changing diagnostic criteria for irritable bowel syndrome from Rome II to Rome
      III may affect women more than men on not only the overall prevalence rate but
      also the sex-difference present or not, especially in irritable bowel syndrome
      with constipation and irritable bowel syndrome unsubtyped subgroups.

PMID- 18339592
TI  - 13C-methacetin-breath test compared to also noninvasive biochemical blood tests
      in predicting hepatic fibrosis and cirrhosis in chronic hepatitis C.
AB  - BACKGROUND: The (13)C-methacetin-breath test and also several noninvasive blood
      tests comprising routine laboratory parameters have been proposed to predict
      fibrosis and cirrhosis in chronic hepatitis C. The aim of the study was to
      compare the diagnostic accuracy between these tests referring to hepatic
      histology as gold standard. METHODS: 96 patients with chronic hepatitis C virus
      infection underwent percutaneous liver biopsy and the (13)C-methacetin-breath
      test. The Fibroindex, the aspartate aminotransferase to platelet ratio index ,
      and the aspartate aminotransferase to alanine aminotransferase ratio were used as
      parameters for the staging of fibrosis. The main endpoint was the area under the
      characteristic curves for the diagnosis of advanced fibrosis (F3-F4) and
      cirrhosis (F4) according to the Batts Ludwig criteria. RESULTS: ROC analysis
      revealed a cut-off <14.6 per thousand best with 92.6% sensitivity and 84.1%
      specificity for the (13)C-methacetin-breath test, for the Fibroindex >1.82 70.4%
      sensitivity and 91.3% specificity, for the aspartate aminotransferase to platelet
      ratio >1.0 a 66.7% sensitivity and 75.4% specificity, and for the aspartate
      aminotransferase to alanine aminotransferase ratio >1.0 63.0% sensitivity and
      59.4% specificity in predicting liver cirrhosis. The areas under the curve for
      the breath test, the Fibroindex, aspartate aminotransferase to platelet ratio and
      the aspartate aminotransferase to alanine aminotransferase ratio were 0.958,
      0.845, 0.799, and 0.688, respectively, when predicting cirrhosis. For identifying
      patients with advanced fibrosis, the areas under the curve were 0.827, 0.804,
      0.779, and 0.561, respectively. Discordances between Fibroindex (21%), aspartate
      aminotransferase to platelet ratio (29%) or aspartate aminotransferase to alanine
      aminotransferase ratio (37.6%) and liver biopsy were significantly more frequent
      than between (13)C-breath test (11.6%) and liver biopsy (P<0.05). CONCLUSION: The
      (13)C-methacetin-breath test is more reliable in predicting advanced fibrosis and
      cirrhosis than simple biochemical parameters (aspartate aminotransferase to
      platelet ratio; aspartate aminotransferase to alanine aminotransferase ratio).

PMID- 18339593
TI  - Bleeding gastric metastatic melanoma.

PMID- 18339594
TI  - Hepatocarcinoma in a child with cholesterol ester storage disease.

PMID- 18339595
TI  - The MELD-Na is an independent short- and long-term prognostic predictor for
      hepatocellular carcinoma: a prospective survey.
AB  - BACKGROUND AND AIM: Serum sodium has been suggested to incorporate into the model
      for end-stage liver disease to enhance its prognostic ability for cirrhosis. A
      mathematical equation based on model for end-stage liver disease and sodium,
      known as "MELD-Na", was developed for outcome prediction for cirrhosis. The
      severity of liver cirrhosis is a key component to predict survival in patients
      with hepatocellular carcinoma. This study investigated the prognostic role of
      MELD-Na for hepatocellular carcinoma. PATIENTS AND METHODS: A total of 535
      unselected hepatocellular carcinoma patients were prospectively enrolled to
      evaluate the performance of MELD-Na. RESULTS: The MELD-Na was better than model
      for end-stage liver disease in predicting 6-month mortality by comparing the area
      under receiver operating characteristic curve (0.782 vs. 0.761, p=0.101). MELD
      Na, but not model for end-stage liver disease, was an independent predictor
      associated with 6-month mortality in multivariate logistic regression analysis
      (odds ratio: 1.14, p=0.001). In the survival analysis, MELD-Na also independently
      predicted mortality, with an additional risk of 4.3% per unit increment of the
      score (p<0.001). Patients with MELD-Na scores between 10 and 20 and scores >20
      had 2.1-fold (p<0.001) and 7.5-fold (p<0.001) risk of mortality, respectively,
      compared to patients with a score <10 in the Cox proportional hazard model.
      CONCLUSION: The MELD-Na score is a feasible and independent prognostic predictor
      for both short- and long-term outcome predictions in patients with hepatocellular
      carcinoma.

PMID- 18339596
TI  - Synergistic effect of paeonol and cisplatin on oesophageal cancer cell lines.
AB  - BACKGROUND/AIM: Paeonol, a phenolic component from the root bark of Paeonia
      moutan, has shown great promise in antitumour activities in our previous studies.
      The present study was designed to investigate whether paeonol has synergistic
      effect with cisplatin on the growth-inhibitory of human oesophageal cancer cell
      lines and the possible mechanism. METHODS: Cell viability was measured by MTT
      assay. Drug-drug interactions were analysed by the coefficient of drug
      interaction. Apoptosis was detected by acridine orange fluorescence staining and
      flow cytometry assay. Bcl-2, Bax and caspase-3 expression was assayed by
      immunohistochemical staining. RESULTS: A synergistic inhibitory effect on
      viability of the two cell lines was observed after combination of paeonol with
      various concentrations of cisplatin. Further study showed the combination induced
      greater apoptosis than the groups treated with paeonol or cisplatin alone. The
      expression of Bcl-2 was decreased and that of Bax was increased in treatment
      groups, especially in the combination group, with the ratio of Bcl-2/Bax
      decreased correspondingly. And the combination also resulted in greater
      activation of caspase-3 than did either agent alone. CONCLUSIONS: Paeonol, in
      combination with cisplatin, had a significantly synergistic growth-inhibitory
      effect on oesophageal cell line, which may be related to apoptosis induction.

PMID- 18339597
TI  - Advanced technology in the management of fibrous dysplasia.
AB  - BACKGROUND: The aim of this paper is to describe the applications of advanced
      imaging technology in optimising the surgical management of complex craniofacial
      fibrous dysplasia (FD). METHODS: Preoperative planning involved a number of
      advanced technologies. Haptic modelling was used to simulate tumour excision and
      the design of the osteotomies, on a virtual 3D computerised tomographic (CT)
      scan. Rapid prototyping was employed in fabricating a physical prototype of the
      skull, featuring the ideal, symmetrical reconstruction. Tumour extirpation was
      carried out with the aid of stereotactic navigation. Intraoperatively, resorbable
      mesh is moulded precisely to the shape of the skull prototype, thereby
      transferring the surgical simulation to the patient in the operating room. The
      resorbable mesh serves as a template which guides the shape and spatial
      orientation of an autologous bone graft reconstruction. Pre- and postoperative
      volumetric differences were assessed to determine the accuracy of the final
      results. RESULTS: Short and long term follow-up examinations show excellent
      cosmetic outcome, with significant restoration of volumetric symmetry.
      CONCLUSIONS: The added complexity of using the new technologies increases
      preoperative planning time, but we believe that this is offset by the improved
      safety during the resection of the tumours as well as the excellent aesthetic
      outcomes.

PMID- 18339598
TI  - Introduction. Japan: its tradition and hot topics in biological sciences.

PMID- 18339599
TI  - Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key
      molecule responsible for long-term depression, endocannabinoid signalling and
      synapse elimination.
AB  - The cerebellum is a brain structure involved in the coordination, control and
      learning of movements, and elucidation of its function is an important issue.
      Japanese scholars have made seminal contributions in this field of neuroscience.
      Electrophysiological studies of the cerebellum have a long history in Japan since
      the pioneering works by Ito and Sasaki. Elucidation of the basic circuit diagram
      of the cerebellum in the 1960s was followed by the construction of cerebellar
      network theories and finding of their neural correlates in the 1970s. A
      theoretically predicted synaptic plasticity, long-term depression (LTD) at
      parallel fibre to Purkinje cell synapse, was demonstrated experimentally in 1982
      by Ito and co-workers. Since then, Japanese neuroscientists from various
      disciplines participated in this field and have made major contributions to
      elucidate molecular mechanisms underlying LTD. An important pathway for LTD
      induction is type-1 metabotropic glutamate receptor (mGluR1) and its downstream
      signal transduction in Purkinje cells. Sugiyama and co-workers demonstrated the
      presence of mGluRs and Nakanishi and his pupils identified the molecular
      structures and functions of the mGluR family. Moreover, the authors contributed
      to the discovery and elucidation of several novel functions of mGluR1 in
      cerebellar Purkinje cells. mGluR1 turned out to be crucial for the release of
      endocannabinoid from Purkinje cells and the resultant retrograde suppression of
      transmitter release. It was also found that mGluR1 and its downstream signal
      transduction in Purkinje cells are indispensable for the elimination of redundant
      synapses during post-natal cerebellar development. This article overviews the
      seminal works by Japanese neuroscientists, focusing on mGluR1 signalling in
      cerebellar Purkinje cells.

PMID- 18339600
TI  - Towards understanding of the cortical network underlying associative memory.
AB  - Declarative knowledge and experiences are represented in the association cortex
      and are recalled by reactivation of the neural representation.
      Electrophysiological experiments have revealed that associations between
      semantically linked visual objects are formed in neural representations in the
      temporal and limbic cortices. Memory traces are created by the reorganization of
      neural circuits. These regions are reactivated during retrieval and contribute to
      the contents of a memory. Two different types of retrieval signals are suggested
      as follows: automatic and active. One flows backward from the medial temporal
      lobe during the automatic retrieval process, whereas the other is conveyed as a
      top-down signal from the prefrontal cortex to the temporal cortex during the
      active retrieval process. By sending the top-down signal, the prefrontal cortex
      manipulates and organizes to-be-remembered information, devises strategies for
      retrieval and monitors the outcome. To further understand the neural mechanism of
      memory, the following two complementary views are needed: how the multiple
      cortical areas in the brain-wide network interact to orchestrate cognitive
      functions and how the properties of single neurons and their synaptic connections
      with neighbouring neurons combine to form local circuits and to exhibit the
      function of each cortical area. We will discuss some new methodological
      innovations that tackle these challenges.

PMID- 18339601
TI  - Neural stem cells: involvement in adult neurogenesis and CNS repair.
AB  - Recent advances in stem cell research, including the selective expansion of
      neural stem cells (NSCs) in vitro, the induction of particular neural cells from
      embryonic stem cells in vitro, the identification of NSCs or NSC-like cells in
      the adult brain and the detection of neurogenesis in the adult brain (adult
      neurogenesis), have laid the groundwork for the development of novel therapies
      aimed at inducing regeneration in the damaged central nervous system (CNS). There
      are two major strategies for inducing regeneration in the damaged CNS: (i)
      activation of the endogenous regenerative capacity and (ii) cell transplantation
      therapy. In this review, we summarize the recent findings from our group and
      others on NSCs, with respect to their role in insult-induced neurogenesis
      (activation of adult NSCs, proliferation of transit-amplifying cells, migration
      of neuroblasts and survival and maturation of the newborn neurons), and
      implications for therapeutic interventions, together with tactics for using cell
      transplantation therapy to treat the damaged CNS.

PMID- 18339602
TI  - Stochastic rotational catalysis of proton pumping F-ATPase.
AB  - F-ATPases synthesize ATP from ADP and phosphate coupled with an electrochemical
      proton gradient in bacterial or mitochondrial membranes and can hydrolyse ATP to
      form the gradient. F-ATPases consist of a catalytic F1 and proton channel F0
      formed from the alpha3beta3gammadelta and ab2c10 subunit complexes, respectively.
      The rotation of gammaepsilonc10 couples catalyses and proton transport.
      Consistent with the threefold symmetry of the alpha3beta3 catalytic hexamer, 120
      degrees stepped revolution has been observed, each step being divided into two
      substeps. The ATP-dependent revolution exhibited stochastic fluctuation and was
      driven by conformation transmission of the beta subunit (phosphate-binding P
      loop/alpha-helix B/loop/beta-sheet4). Recent results regarding mechanically
      driven ATP synthesis finally proved the role of rotation in energy coupling.

PMID- 18339603
TI  - Nanobiomechanics of proteins and biomembrane.
AB  - A review of the work done in the Laboratory of Biodynamics of Tokyo Institute of
      Technology in the last decade has been summarized in this article in relation to
      the results reported from other laboratories. The emphasis here is the
      application of nanomechanics based on the force mode of atomic force microscopy
      (AFM) to proteins and protein-based biological structures. Globular proteins were
      stretched in various ways to detect the localized rigidity inside of the
      molecule. When studied by this method, bovine carbonic anhydrase II (BCA II),
      calmodulin and OspA protein all showed the presence of localized rigid structures
      inside the molecules. Protein compression experiments were done on BCA II to
      obtain an estimate of the Young modulus and its change in the process of
      denaturation. Then, the AFM probe method was turned on to cell membranes and
      cytoplasmic components. Force curves accompanying the extraction process of
      membrane proteins from intact cells were analysed in relation to their
      interaction with the cytoskeletal components. By pushing the AFM probe further
      into the cytoplasm, mRNAs were recovered from a live cell with minimal damage,
      and multiplied using PCR technology for their identification. Altogether, the
      work introduced here forms the basis of nanomechanics of protein and protein
      based biostructures and application of the nanomechanical technology to cell
      biology.

PMID- 18339604
TI  - Phase contrast electron microscopy: development of thin-film phase plates and
      biological applications.
AB  - Phase contrast transmission electron microscopy (TEM) based on thin-film phase
      plates has been developed and applied to biological systems. Currently,
      development is focused on two techniques that employ two different types of phase
      plates. The first technique uses a Zernike phase plate, which is made of a
      uniform amorphous carbon film that completely covers the aperture of an objective
      lens and can retard the phase of electron waves by pi/2, except at the centre
      where a tiny hole is drilled. The other technique uses a Hilbert phase plate,
      which is made of an amorphous carbon film that is twice as thick as the Zernike
      phase plate, covers only half of the aperture and retards the electron wave phase
      by pi. By combining the power of efficient phase contrast detection with the
      accurate preservation achieved by a cryotechnique such as vitrification,
      macromolecular complexes and supermolecular structures inside intact bacterial or
      eukaryotic cells may be visualized without staining. Phase contrast cryo-TEM has
      the potential to bridge the gap between cellular and molecular biology in terms
      of high-resolution visualization. Examples using proteins, viruses, cyanobacteria
      and somatic cells are provided.

PMID- 18339605
TI  - Single molecule measurements and molecular motors.
AB  - Single molecule imaging and manipulation are powerful tools in describing the
      operations of molecular machines like molecular motors. The single molecule
      measurements allow a dynamic behaviour of individual biomolecules to be measured.
      In this paper, we describe how we have developed single molecule measurements to
      understand the mechanism of molecular motors. The step movement of molecular
      motors associated with a single cycle of ATP hydrolysis has been identified. The
      single molecule measurements that have sensitivity to monitor thermal fluctuation
      have revealed that thermal Brownian motion is involved in the step movement of
      molecular motors. Several mechanisms have been suggested in different motors to
      bias random thermal motion to directional movement.

PMID- 18339606
TI  - Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome:
      myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic
      events in TACTICS-TIMI 18.
AB  - AIMS: We investigated the prognostic performance of myeloperoxidase (MPO), and
      soluble CD40 ligand (sCD40L) along with B-type natriuretic peptide (BNP), high
      sensitivity C-reactive protein (hsCRP), and cardiac troponin I (cTnI) for non
      fatal recurrent ischaemic events in non-ST elevation acute coronary syndrome
      (ACS). METHODS AND RESULTS: We measured plasma MPO and sCD40L in 1524 patients
      with ACS treated with tirofiban and randomized to early invasive vs. conservative
      management in the TACTICS-TIMI 18 trial who survived to 180 days. Patients with
      elevated baseline MPO (>884 pM) were at higher risk of non-fatal myocardial
      infarction or rehospitalization for ACS at 30 days (9.3 vs. 4.6%, P < 0.001). In
      contrast, no difference was observed with higher sCD40L (>989 pg/mL, 7.6 vs.
      6.3%, P = 0.31). MPO remained associated with recurrent ischaemic events after
      adjustment for age, ST-deviation, diabetes, prior coronary artery disease, heart
      failure, cTnI, hsCRP, and sCD40L (OR 2.10; 95% CI 1.36-3.23, P = 0.001). This
      association was attenuated by 180 days (OR 1.26; 0.95-1.68). Stratification using
      baseline MPO, BNP, and cTnI identified a >3-fold gradient of risk. CONCLUSION:
      MPO adds to BNP and cTnI for short-term risk assessment for recurrent ischaemic
      events in non-ST elevation ACS. sCD40L was not associated with risk in this
      population treated with a platelet GPIIb/IIIa receptor antagonist.

PMID- 18339607
TI  - Prevalence and significance of unrecognized renal insufficiency in patients with
      heart failure.
AB  - AIMS: Renal insufficiency (RI) is a strong predictor of adverse outcome in
      patients with heart failure (HF). We aimed to determine the prevalence of RI
      being unrecognized and its significance in patients hospitalized with HF. METHODS
      AND RESULTS: We analysed data from a prospective survey of 4102 hospitalized
      patients with HF. RI [defined as estimated glomerular filtration rate (eGFR) <60
      mL/min/1.73 m2] was present in 2145 (57%) patients but, based on medical records,
      was unrecognized in 872 [41%, 95% confidence interval (CI) 39-43%] of them.
      Patients with unrecognized RI were more likely to be women, elderly, and with
      better functional class, compared with patients with recognized RI. In-hospital
      and 1 year mortality was significantly higher among patients with recognized and
      unrecognized RI compared with patients without RI: 6.5 and 7.1 vs. 2.1%, and 38.8
      and 30.9 vs. 18.8% (P < 0.001), respectively. After adjustment, recognized and
      unrecognized RI comparably predicted increased in-hospital mortality: odds ratio
      (OR) and 95% CI of 2.34 (1.43-3.87), P < 0.001, and 2.30 (1.45-3.72), P < 0.001.
      After 1 year, recognized RI remained an independent predictor for mortality: OR
      1.79 (1.45-2.20), P < 0.001, whereas there was a trend for increased mortality
      predicted by unrecognized RI: OR 1.22 (0.97-1.53), P = 0.08. CONCLUSION: A high
      proportion of RI remains unrecognized among hospitalized patients with HF. As co
      morbid RI has important prognostic and therapeutic implications, patients with HF
      may benefit from routine assessment of GFR.

PMID- 18339608
TI  - Tilt testing potentiated with sublingual nitroglycerin in children with
      unexplained syncope.

PMID- 18339609
TI  - Postural tachycardia syndrome and coronary artery bridge.
AB  - Postural tachycardia syndrome (POTS) is characterized by the presence of
      orthostatic tachycardia in the absence of orthostatic hypotension with a heart
      rate increase of >or=30 bpm. Patients often relate complaints of palpitations,
      exercise intolerance, fatigue and near-syncope or syncope, other non-specific
      symptoms such as headache and nausea may be present as well to varying degrees.
      Myocardial bridging is rare occurring in 0.5-16% in angiographic studies.
      Clinical presentation is protean and can manifest as atrioventricular blockade,
      ventricular tachycardia, myocardial ischaemia, sudden cardiac death, and
      myocardial infarction. However, the majority of patients with myocardial bridging
      are asymptomatic. We describe a case of POTS syndrome and myocardial bridging co
      existing and presenting a therapeutic challenge.

PMID- 18339610
TI  - Reversal of premature ventricular complex-induced cardiomyopathy following
      successful radiofrequency catheter ablation.
AB  - Premature ventricular complex (PVC)-induced cardiomyopathy is an underappreciated
      cause of left-ventricular (LV) dysfunction. The present report describes the case
      of an elderly man with a very high burden of monomorphic PVCs and LV dysfunction.
      Elimination of the left ventricular focus following radiofrequency catheter
      ablation resulted in reversal of cardiomyopathy.

PMID- 18339611
TI  - Novel non-pharmacological approaches for antiarrhythmic therapy of atrial
      fibrillation.
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical
      practice. Its prevalence is increasing in our ageing population, and it has a
      soaring impact on health systems. It can cause thrombo-embolism, heart failure,
      and hospitalizations, and is associated with a two-fold increase in all-cause
      mortality. There have been great advances in understanding the mechanism of AF
      that are currently being translated into new therapeutic concepts. Experimental
      studies demonstrated that AF-induced electrical and structural remodelling of the
      fibrillating atria perpetuate AF ('AF begets AF'). Furthermore, there is growing
      understanding that the atria are an endocrine organ expressing angiotensin and
      thrombogenic substances. Clinical, electrophysiological studies have identified
      automatic triggers, often in the pulmonary veins, that initiate paroxysmal AF.
      Electrical isolation of the pulmonary veins by circular ablation abolishes these
      triggers. Whereas isolation of the pulmonary veins often maintains sinus rhythm
      in patients with paroxysmal AF, additional ablation strategies are used in
      persistent and permanent AF to modify the more complex electrical and structural
      atrial changes. The 'role model' for extensive ablation in the left atrium is the
      surgical MAZE procedure that abolishes long-standing AF by cutting and sewing the
      atria into complex pieces. New surgical approaches of AF therapy use
      radiofrequency or other sources for an easy ablation during open-heart surgery. A
      lot of effort has also been put in the development of device therapy for the
      treatment of AF, with mixed effects on maintenance of sinus rhythm, but
      unexpected insights into the development of asymptomatic AF recurrences. This
      review aims to provide an overview of these non-pharmacological treatment options
      of AF in the context of potential pathophysiological processes.

PMID- 18339612
TI  - Atrioventricular junction ablation and pacemaker implant for atrial fibrillation:
      still a valid treatment in appropriately selected patients.
AB  - This review explores the current techniques of atrioventricular junction
      ablation, pacemaker prescription and implant, the role of anti-arrhythmic drugs,
      long-term outcomes, potential complications and adverse effects (including sudden
      cardiac death), and how these may be overcome, and examines the alternative
      strategies that are now available.

PMID- 18339613
TI  - Spinal cord stimulation affects T-wave alternans in patients with ischaemic
      cardiomyopathy: a pilot study.
AB  - AIMS: An antiarrhythmic effect of spinal cord stimulation (SCS) has been
      recognized in an animal model. The actual mechanism is still mainly unknown. An
      adrenergic output reduction has been advocated as the main mechanism, although a
      modulation effect on the arrhythmic substrate has not yet been investigated. We
      studied T-wave alternans (TWA) modifications to test the hypothesis that SCS
      affects the arrhythmic substrate. METHODS AND RESULTS: We performed TWA
      assessment in three high-risk patients who previously had undergone implantation
      of both implantable cardioverter defibrillator and SCS to treat refractory
      angina. The test was performed after switching off the SCS and after 2 and 24 h
      stimulation at the default amplitude. The protocol was executed 2 months apart in
      order to assess the reproducibility of the results, collecting a total of 18 TWA
      reports. In all the three patients, we observed a significant reduction of TWA
      amplitude after 2 h stimulation. All the tests were classified as negative after
      24 h stimulation with the nominal parameters. CONCLUSION: Spinal cord stimulation
      results in a decrease in the TWA magnitude, and thus it seems to positively
      affect the arrhythmic substrate in a time-dependent manner.

PMID- 18339614
TI  - Systemic inflammatory changes after pulmonary vein radiofrequency ablation do not
      alter stem cell mobilization.
AB  - AIMS: Aim of this study was to investigate the number of circulating progenitor
      cells, systemic inflammatory mediators, and myocardial necrosis in patients with
      paroxysmal atrial fibrillation (AF) undergoing pulmonary vein (PV) isolation by
      radiofrequency (RF) ablation. Radiofrequency ablation generates a localized
      myocardial necrosis that might result in a release of inflammatory mediators
      enhancing progenitor cell mobilization and improving tissue repair. METHODS AND
      RESULTS: Blood samples were collected in patients with paroxysmal AF before and
      after PV isolation. Interleukin (IL)-6, IL-1beta, TNF-alpha, IL-8, IL-10, and IL
      12, and stromal derived factor (SDF)-1 were measured by immunoassay. CD34+CD133+,
      CD117+, and endothelial progenitor cells (EPCs) were analysed by flow cytometry
      and culture assay. After ablation procedure, a rise in creatine kinase and
      troponin T levels indicated myocardial necrosis. Leukocyte counts and C-reactive
      protein and IL-6 levels increased significantly. Myocardial necrosis and
      inflammatory response correlated with an increase in IL-6 (P = 0.007). In
      contrast, SDF-1 levels decreased after RF ablation (P = 0.004). Yet, no
      significant changes were observed in IL-1beta, TNF-alpha, IL-8, IL 10, and IL-12
      plasma levels or in the number of circulating CD34+CD133+ and CD117+ progenitor
      cells, whereas EPCs decreased by trend. CONCLUSION: Although PV isolation by RF
      ablation in patients with paroxysmal AF induces a systemic inflammatory response
      associated with myocardial necrosis, no alterations in circulating progenitor
      cells were observed. Thus, isolated myocardial necrosis may not be sufficient to
      account for progenitor cell mobilization.

PMID- 18339615
TI  - Glucose control levels, ischaemic brain lesions, and hyperinsulinaemia were
      associated with cognitive dysfunction in diabetic elderly.

PMID- 18339616
TI  - An evaluation of palliative care in the acute geriatric setting.

PMID- 18339617
TI  - Predicting length of hospitalisation of elderly patients, using the Barthel
      Index.

PMID- 18339618
TI  - Serum testosterone but not leptin predicts mortality in elderly men.

PMID- 18339619
TI  - Structures of rhodopsin kinase in different ligand states reveal key elements
      involved in G protein-coupled receptor kinase activation.
AB  - G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated
      heptahelical receptors, leading to their uncoupling from G proteins. Here we
      report six crystal structures of rhodopsin kinase (GRK1), revealing not only
      three distinct nucleotide-binding states of a GRK but also two key structural
      elements believed to be involved in the recognition of activated GPCRs. The first
      is the C-terminal extension of the kinase domain, which was observed in all
      nucleotide-bound GRK1 structures. The second is residues 5-30 of the N terminus,
      observed in one of the GRK1.(Mg2+)2.ATP structures. The N terminus was also
      clearly phosphorylated, leading to the identification of two novel
      phosphorylation sites by mass spectral analysis. Co-localization of the N
      terminus and the C-terminal extension near the hinge of the kinase domain
      suggests that activated GPCRs stimulate kinase activity by binding to this region
      to facilitate full closure of the kinase domain.

PMID- 18339620
TI  - Miniaturization of scorpion beta-toxins uncovers a putative ancestral surface of
      interaction with voltage-gated sodium channels.
AB  - The bioactive surface of scorpion beta-toxins that interact with receptor site-4
      at voltage-gated sodium channels is constituted of residues of the conserved
      betaalphabetabeta core and the C-tail. In an attempt to evaluate the extent by
      which residues of the toxin core contribute to bioactivity, the anti-insect and
      anti-mammalian beta-toxins Bj-xtrIT and Css4 were truncated at their N and C
      termini, resulting in miniature peptides composed essentially of the core
      secondary structure motives. The truncated beta-toxins (DeltaDeltaBj-xtrIT and
      DeltaDeltaCss4) were non-toxic and did not compete with the parental toxins on
      binding at receptor site-4. Surprisingly, DeltaDeltaBj-xtrIT and DeltaDeltaCss4
      were capable of modulating in an allosteric manner the binding and effects of
      site-3 scorpion alpha-toxins in a way reminiscent of that of brevetoxins, which
      bind at receptor site-5. While reducing the binding and effect of the scorpion
      alpha-toxin Lqh2 at mammalian sodium channels, they enhanced the binding and
      effect of LqhalphaIT at insect sodium channels. Co-application of DeltaDeltaBj
      xtrIT or DeltaDeltaCss4 with brevetoxin abolished the brevetoxin effect, although
      they did not compete in binding. These results denote a novel surface at
      DeltaDeltaBj-xtrIT and DeltaDeltaCss4 capable of interaction with sodium channels
      at a site other than sites 3, 4, or 5, which prior to the truncation was masked
      by the bioactive surface that interacts with receptor site-4. The disclosure of
      this hidden surface at both beta-toxins may be viewed as an exercise in "reverse
      evolution," providing a clue as to their evolution from a smaller ancestor of
      similar scaffold.

PMID- 18339621
TI  - Ablation of Ca2+ channel beta3 subunit leads to enhanced N-methyl-D-aspartate
      receptor-dependent long term potentiation and improved long term memory.
AB  - The beta subunits of voltage-dependent Ca(2+) channels (VDCCs) have marked
      effects on the properties of the pore-forming alpha(1) subunits of VDCCs,
      including surface expression of channel complexes and modification of voltage
      dependent kinetics. Among the four different beta subunits, the beta(3) subunit
      (Ca(v)beta3) is abundantly expressed in the hippocampus. However, the role of
      Ca(v)beta3 in hippocampal physiology and function in vivo has never been
      examined. Here, we investigated Ca(v)beta3-deficient mice for hippocampus
      dependent learning and memory and synaptic plasticity at hippocampal CA3-CA1
      synapses. Interestingly, the mutant mice exhibited enhanced performance in
      several hippocampus-dependent learning and memory tasks. However,
      electrophysiological studies revealed no alteration in the Ca(2+) current
      density, the frequency and amplitude of miniature excitatory postsynaptic
      currents, and the basal synaptic transmission in the mutant hippocampus. On the
      other hand, however, N-methyl-d-aspartate receptor (NMDAR)-mediated synaptic
      currents and NMDAR-dependent long term potentiation were significantly increased
      in the mutant. Protein blot analysis showed a slight increase in the level of
      NMDAR-2B in the mutant hippocampus. Our results suggest a possibility that,
      unrelated to VDCCs regulation, Ca(v)beta3 negatively regulates the NMDAR activity
      in the hippocampus and thus activity-dependent synaptic plasticity and cognitive
      behaviors in the mouse.

PMID- 18339622
TI  - Investigating the regulation of brain-specific kinases 1 and 2 by
      phosphorylation.
AB  - Brain-specific kinases 1 and 2 (BRSK1/2) are AMP-activated protein kinase (AMPK)
      related kinases that are highly expressed in mammalian forebrain. Studies using
      transgenic animal models have implicated a role for these kinases in the
      establishment of neuronal polarity. BRSK1 and BRSK2 are activated by
      phosphorylation of a threonine residue in the T-loop activation segment of the
      kinase domain. In vitro studies have demonstrated that LKB1, an upstream kinase
      in the AMPK cascade, can catalyze this phosphorylation. However, to date, a
      detailed comparative analysis of the molecular regulation of BRSK1/2 has not been
      undertaken. Here we present evidence that excludes another upstream kinase in the
      AMPK cascade, Ca(2+)/calmodulin-dependent protein kinase kinase beta, from a role
      in activating BRSK1/2. We show that equivalent mutations in the ubiquitin
      associated domains of the BRSK isoforms produce differential effects on the
      activation of BRSK1 and BRSK2. Contrary to previous reports, activation of cAMP
      dependent protein kinase does not affect BRSK1 or BRSK2 activity in mammalian
      cells. Furthermore, stimuli that activate AMPK had no effect on BRSK1/2. Finally,
      we provide evidence suggesting that protein phosphatase 2C is a likely candidate
      for catalyzing the dephosphorylation and inactivation of BRSK1/2.

PMID- 18339623
TI  - The plant defensin, NaD1, enters the cytoplasm of Fusarium oxysporum hyphae.
AB  - The plant defensin, NaD1, from the flowers of Nicotiana alata displays potent
      antifungal activity against a variety of agronomically important filamentous
      fungi including Fusarium oxysporum f. sp. vasinfectum (Fov). To understand the
      mechanism of this antifungal activity, the effect of NaD1 on Fov fungal membranes
      and the location of NaD1 in treated hyphae was examined using various
      fluorescence techniques. NaD1 permeabilized fungal plasma membranes via the
      formation of an aperture with an internal diameter of between 14 and 22A. NaD1
      bound to the cell walls of all treated hyphae and entered several hyphae,
      resulting in granulation of the cytoplasm and cell death. These results suggest
      that the activity of antifungal plant defensins may not be restricted to the
      hyphal membrane and that they enter cells and affect intracellular targets.

PMID- 18339624
TI  - Human IgG2 antibodies display disulfide-mediated structural isoforms.
AB  - In this work, we present studies of the covalent structure of human IgG2
      molecules. Detailed analysis showed that recombinant human IgG2 monoclonal
      antibody could be partially resolved into structurally distinct forms caused by
      multiple disulfide bond structures. In addition to the presently accepted
      structure for the human IgG2 subclass, we also found major structures that differ
      from those documented in the current literature. These novel structural isoforms
      are defined by the light chain constant domain (C(L)) and the heavy chain C(H)1
      domain covalently linked via disulfide bonds to the hinge region of the molecule.
      Our results demonstrate the presence of three main types of structures within the
      human IgG2 subclass, and we have named these structures IgG2-A, -B, and -A/B.
      IgG2-A is the known classic structure for the IgG2 subclass defined by
      structurally independent Fab domains and hinge region. IgG2-B is a structure
      defined by a symmetrical arrangement of a (C(H)1-C(L)-hinge)(2) complex with both
      Fab regions covalently linked to the hinge. IgG2-A/B represents an intermediate
      form, defined by an asymmetrical arrangement involving one Fab arm covalently
      linked to the hinge through disulfide bonds. The newly discovered structural
      isoforms are present in native human IgG2 antibodies isolated from myeloma plasma
      and from normal serum. Furthermore, the isoforms are present in native human IgG2
      with either kappa or lambda light chains, although the ratios differ between the
      light chain classes. These findings indicate that disulfide structural
      heterogeneity is a naturally occurring feature of antibodies belonging to the
      human IgG2 subclass.

PMID- 18339625
TI  - The Med1 subunit of transcriptional mediator plays a central role in regulating
      CCAAT/enhancer-binding protein-beta-driven transcription in response to
      interferon-gamma.
AB  - Transcription factor CCAAT/enhancer-binding protein (C/EBP)-beta is crucial for
      regulating transcription of genes involved in a number of diverse cellular
      processes, including those involved in some cytokine-induced responses. However,
      the mechanisms that contribute to its diverse transcriptional activity are not
      yet fully understood. To gain an understanding into its mechanisms of action, we
      took a proteomic approach and identified cellular proteins that associate with
      C/EBP-beta in an interferon (IFN)-gamma-dependent manner. Transcriptional
      mediator (Mediator) is a multisubunit protein complex that regulates signal
      induced cellular gene transcription from enhancer-bound transcription factor(s).
      Here, we report that the Med1 subunit of the Mediator as a C/EBP-beta-interacting
      protein. Using gene knock-out cells and mutational and RNA interference
      approaches, we show that Med1 is critical for IFN-induced expression of certain
      genes. Med1 associates with C/EBP-beta through a domain located between amino
      acids 125 and 155 of its N terminus. We also show that the MAPK, ERK1/2, and an
      ERK phosphorylation site within regulatory domain 2, more specifically the
      Thr(189) residue, of C/EBP-beta are essential for it to bind to Med1. Last, an
      ERK-regulated site in Med1 protein is also essential for up-regulating IFN
      induced transcription although not critical for binding to C/EBP-beta.

PMID- 18339626
TI  - Structural and functional characterization of disulfide isoforms of the human
      IgG2 subclass.
AB  - In the accompanying report ( Wypych, J., Li, M., Guo, A., Zhang, Z., Martinez,
      T., Allen, M. J., Fodor, S., Kelner, D. N., Flynn, G. C., Liu, Y. D., Bondarenko,
      P. V., Ricci, M. S., Dillon, T. M., and Balland, A. (2008) J. Biol. Chem. 283,
      16194-16205 ), we have identified that the human IgG2 subclass exists as an
      ensemble of distinct isoforms, designated IgG2-A, -B, and -A/B, which differ by
      the disulfide connectivity at the hinge region. In this report, we studied the
      structural and functional properties of the IgG2 disulfide isoforms and compared
      them to IgG1. Human monoclonal IgG1 and IgG2 antibodies were designed with
      identical antigen binding regions, specific to interleukin-1 cell surface
      receptor type 1. In vitro biological activity measurements showed an increased
      activity of the IgG1 relative to the IgG2 in blocking interleukin-1beta ligand
      from binding to the receptor, suggesting that some of the IgG2 isoforms had lower
      activity. Under reduction-oxidation conditions, the IgG2 disulfide isoforms
      converted to IgG2-A when 1 m guanidine was used, whereas IgG2-B was enriched in
      the absence of guanidine. The relative potency of the antibodies in cell-based
      assays was: IgG1 > IgG2-A > IgG2 >> IgG2-B. This difference correlated with an
      increased hydrodynamic radius of IgG2-A relative to IgG2-B, as shown by
      biophysical characterization. The enrichment of disulfide isoforms and activity
      studies were extended to additional IgG2 monoclonal antibodies with various
      antigen targets. All IgG2 antibodies displayed the same disulfide conversion, but
      only a subset showed activity differences between IgG2-A and IgG2-B.
      Additionally, the distribution of isoforms was influenced by the light chain
      type, with IgG2lambda composed mostly of IgG2-A. Based on crystal structure
      analysis, we propose that IgG2 disulfide exchange is caused by the close
      proximity of several cysteine residues at the hinge and the reactivity of tandem
      cysteines within the hinge. Furthermore, the IgG2 isoforms were shown to
      interconvert in whole blood or a "blood-like" environment, thereby suggesting
      that the in vivo activity of human IgG2 may be dependent on the distribution of
      isoforms.

PMID- 18339627
TI  - Mammalian target of rapamycin contributes to the acquired apoptotic resistance of
      human mesothelioma multicellular spheroids.
AB  - When grown as three-dimensional structures, tumor cells can acquire an additional
      multicellular resistance to apoptosis that may mimic the chemoresistance found in
      solid tumors. We developed a multicellular spheroid model of malignant
      mesothelioma to investigate molecular mechanisms of acquired apoptotic
      resistance. We found that mesothelioma cell lines, when grown as multicellular
      spheroids, acquired resistance to a variety of apoptotic stimuli, including
      combinations of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL),
      ribotoxic stressors, histone deacetylase, and proteasome inhibitors, that were
      highly effective against mesothelioma cells when grown as monolayers. Inhibitors
      of the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)
      pathway, particularly rapamycin, blocked much of the acquired resistance of the
      spheroids, suggesting a key role for mTOR. Knockdown by small interference RNA of
      S6K, a major downstream target of mTOR, reproduced the effect of rapamycin,
      thereby confirming the role of mTOR and of S6K in the acquired resistance of
      three dimensional spheroids. Rapamycin or S6K knockdown increased TRAIL-induced
      caspase-8 cleavage in spheroids, suggesting initially that mTOR inhibited
      apoptosis by actions at the death receptor pathway; however, isolation of the
      apoptotic pathways by means of Bid knockdown ablated this effect showing that
      mTOR actually controls a step distal to Bid, probably at the level of the
      mitochondria. In sum, mTOR and S6K contribute to the apoptotic resistance of
      mesothelioma cells in three-dimensional, not in two-dimensional, cultures. The
      three-dimensional model may reflect a more clinically relevant in vitro setting
      in which mTOR exhibits anti-apoptotic properties.

PMID- 18339628
TI  - NfuA, a new factor required for maturing Fe/S proteins in Escherichia coli under
      oxidative stress and iron starvation conditions.
AB  - Iron/sulfur (Fe/S) proteins are central to the functioning of cells in both
      prokaryotes and eukaryotes. Here, we show that the yhgI gene, which we renamed
      nfuA, encodes a two-domain protein that is required for Fe/S biogenesis in
      Escherichia coli. The N-terminal domain resembles the so-called Fe/S A-type
      scaffold but, curiously, has lost the functionally important Cys residues. The C
      terminal domain shares sequence identity with Nfu proteins. Mossbauer and UV
      visible spectroscopic analyses revealed that, upon reconstitution, NfuA binds a
      [4Fe-4S] cluster. Moreover, NfuA can transfer this cluster to apo-aconitase.
      Mutagenesis studies indicated that the N- and C-terminal domains are important
      for NfuA function in vivo. Similarly, the functional importance of Cys residues
      present in the Nfu-like domain was demonstrated in vivo by introducing Cys-->Ser
      mutations. In vivo investigations revealed that the nfuA gene is important for E.
      coli to sustain oxidative stress and iron starvation. Also, combining nfuA with
      either isc or suf mutations led to additive phenotypic deficiencies, indicating
      that NfuA is a bona fide new player in Isc- and Suf-dependent Fe/S biogenesis
      pathways. Taken together, these data demonstrate that NfuA intervenes in the
      maturation of apoproteins in E. coli, allowing them to acquire Fe/S clusters. By
      taking into account results from numerous previous transcriptomic studies that
      had suggested a link between NfuA and protein misfolding, we discuss the
      possibility that NfuA could act as a scaffold/chaperone for damaged Fe/S
      proteins.

PMID- 18339629
TI  - A proposed role for the Azotobacter vinelandii NfuA protein as an intermediate
      iron-sulfur cluster carrier.
AB  - Iron-sulfur clusters ([Fe-S] clusters) are assembled on molecular scaffolds and
      subsequently used for maturation of proteins that require [Fe-S] clusters for
      their functions. Previous studies have shown that Azotobacter vinelandii produces
      at least two [Fe-S] cluster assembly scaffolds: NifU, required for the maturation
      of nitrogenase, and IscU, required for the general maturation of other [Fe-S]
      proteins. A. vinelandii also encodes a protein designated NfuA, which shares
      amino acid sequence similarity with the C-terminal region of NifU. The activity
      of aconitase, a [4Fe-4S] cluster-containing enzyme, is markedly diminished in a
      strain containing an inactivated nfuA gene. This inactivation also results in a
      null-growth phenotype when the strain is cultivated under elevated oxygen
      concentrations. NifU has a limited ability to serve the function of NfuA, as its
      expression at high levels corrects the defect of the nfuA-disrupted strain.
      Spectroscopic and analytical studies indicate that one [4Fe-4S] cluster can be
      assembled in vitro within a dimeric form of NfuA. The resultant [4Fe-4S] cluster
      loaded form of NfuA is competent for rapid in vitro activation of apo-aconitase.
      Based on these results a model is proposed where NfuA could represent a class of
      intermediate [Fe-S] cluster carriers involved in [Fe-S] protein maturation.

PMID- 18339630
TI  - Targeted disruption of NeuroD, a proneural basic helix-loop-helix factor, impairs
      distal lung formation and neuroendocrine morphology in the neonatal lung.
AB  - Despite the importance of airspace integrity in vertebrate gas exchange, the
      molecular pathways that instruct distal lung formation are poorly understood.
      Recently, we found that fibrillin-1 deficiency in mice impairs alveolar formation
      and recapitulates the pulmonary features of human Marfan syndrome. To further
      elucidate effectors involved in distal lung formation, we performed expression
      profiling analysis comparing the fibrillin-1-deficient and wild-type developing
      lung. NeuroD, a basic helix-loop-helix transcription factor, fulfilled the
      expression criteria for a candidate mediator of distal lung development. We
      investigated its role in murine lung development using genetically targeted
      NeuroD-deficient mice. We found that NeuroD deficiency results in both impaired
      alveolar septation and altered morphology of the pulmonary neuroendocrine cells.
      NeuroD-deficient mice had enlarged alveoli associated with reduced epithelial
      proliferation in the airway and airspace compartments during development.
      Additionally, the neuroendocrine compartment in these mice manifested an
      increased number of neuroepithelial bodies but a reduced number of solitary
      pulmonary neuroendocrine cells in the neonatal lung. Overexpression of NeuroD in
      a murine lung epithelial cell line conferred a neuroendocrine phenotype
      characterized by the induction of neuroendocrine markers as well as increased
      proliferation. These results support an unanticipated role for NeuroD in the
      regulation of pulmonary neuroendocrine and alveolar morphogenesis and suggest an
      intimate connection between the neuroendocrine compartment and distal lung
      development.

PMID- 18339631
TI  - Targeting of bone morphogenetic protein growth factor complexes to fibrillin.
AB  - Both latent transforming growth factor-beta (TGF-beta)-binding proteins
      fibrillins are components of microfibril networks, and both interact with members
      of the TGF-beta family of growth factors. Interactions between latent TGF-beta
      binding protein-1 and TGF-beta and between fibrillin-1 and bone morphogenetic
      protein-7 (BMP-7) are mediated by the prodomain of growth factor complexes. To
      extend this information, investigations were performed to test whether stable
      complexes are formed by additional selected TGF-beta family members. Using
      velocity sedimentation in sucrose gradients as an assay, complex formation was
      demonstrated for BMP-7 and growth and differentiation factor-8 (GDF-8), which are
      known to exist in prodomain/growth factor complexes. Comparison of these results
      with complex formation by BMP-2, BMP-4 (full-length and shortened propeptides),
      BMP-10, and GDF-5 allowed us to conclude that all, except for BMP-2 and the short
      BMP-4 propeptides, formed complexes with their growth factors. Using surface
      plasmon resonance, binding affinities between fibrillin and all propeptides were
      determined. Binding studies revealed that the N-terminal end of fibrillin-1
      serves as a universal high affinity docking site for the propeptides of BMP-2, 
      4, -7, and -10 and GDF-5, but not GDF-8, and located the BMP/GDF binding site
      within the N-terminal domain in fibrillin-1. Rotary shadowing electron microscopy
      of molecules of BMP-7 complex bound to fibrillin-1 confirmed these findings and
      also showed that prodomain binding targets the growth factor to fibrillin.
      Immunolocalization of BMP-4 demonstrated fibrillar staining limited to certain
      tissues, indicating tissue-specific targeting of BMP-4. These data implicate the
      fibrillin microfibril network in the extracellular control of BMP signaling and
      demonstrate differences in how prodomains target their growth factors to the
      extracellular space.

PMID- 18339632
TI  - A regulatory domain in the N terminus of tryptophan hydroxylase 2 controls enzyme
      expression.
AB  - Serotonin is involved in a variety of physiological processes in the central
      nervous system and the periphery. As the rate-limiting enzyme in serotonin
      synthesis, tryptophan hydroxylase plays an important role in modulating these
      processes. Of the two variants of tryptophan hydroxylase, tryptophan hydroxylase
      2 (TPH2) is expressed predominantly in the central nervous system, whereas
      tryptophan hydroxylase 1 (TPH1) is expressed mostly in peripheral tissues.
      Although the two enzymes share considerable sequence homology, the regulatory
      domain of TPH2 contains an additional 41 amino acids at the N terminus that TPH1
      lacks. Here we show that the extended TPH2 N-terminal domain contains a unique
      sequence involved in the regulation of enzyme expression. When expressed in
      cultured mammalian cells, TPH2 is synthesized less efficiently and is also less
      stable than TPH1. Removal of the unique portion of the N terminus of TPH2 results
      in expression of the enzyme at a level similar to that of TPH1, whereas protein
      chimeras containing this fragment are expressed at lower levels than their wild
      type counterparts. We identify a region centered on amino acids 10-20 that
      mediates the bulk of this effect. We also demonstrate that phosphorylation of
      serine 19, a protein kinase A consensus site located in this N-terminal domain,
      results in increased TPH2 stability and consequent increases in enzyme output in
      cell culture systems. Because this domain is unique to TPH2, these data provide
      evidence for selective regulation of brain serotonin synthesis.

PMID- 18339633
TI  - Guidelines for UK practice for the diagnosis and management of methicillin
      resistant Staphylococcus aureus (MRSA) infections presenting in the community.
AB  - These guidelines have been developed by a Working Party convened on behalf of the
      British Society for Antimicrobial Chemotherapy. Their aim is to provide general
      practitioners and other community- and hospital-based healthcare professionals
      with pragmatic advice about when to suspect MRSA infection in the community, when
      and what cultures should be performed and what should be the management options,
      including the need for hospitalization.

PMID- 18339634
TI  - In vitro activity of conventional antifungal drugs and natural essences against
      the yeast-like alga Prototheca.
AB  - BACKGROUND: Two outbreaks of mastitis due to the yeast-like alga Prototheca
      zopfii recently occurred in dairy herds in Lombardia (Italy) involving 180 and
      150 lactating cows, respectively. OBJECTIVES: To determine the in vitro
      susceptibility of Prototheca isolates to conventional antifungal agents and to
      essential oils. METHODS: Twenty P. zopfii isolated from milk during these
      outbreaks, six P. zopfii isolated from fresh water and two Prototheca sp.
      reference strains were submitted to antifungal susceptibility testing by broth
      microdilution assay following the CLSI guidelines for yeasts. RESULTS: The tested
      isolates were shown to be resistant to fluconazole and caspofungin. A wide range
      of voriconazole MICs was observed. In contrast, amphotericin B, itraconazole and
      posaconazole appeared active with MICs < or = 1 mg/L. Bergamot and tea tree oils
      seemed to exert an interesting activity against this yeast-like alga.
      CONCLUSIONS: Difficulties in treating animals with conventional drugs and the
      potent in vitro activity of essential oils demonstrated here raise the interest
      in further investigations on the therapeutic use of these non-conventional
      natural products.

PMID- 18339635
TI  - Dissemination of extended-spectrum beta-lactamase-producing bacteria: the food
      borne outbreak lesson.
AB  - OBJECTIVES: Commensal and opportunistic bacteria producing extended-spectrum beta
      lactamases (ESBL-PB) have undergone a broad and rapid spread within the general
      population; however, the routes of dissemination have not been totally
      elucidated. The aim of this study was to determine whether individuals involved
      in an outbreak of acute gastroenteritis, in addition to the enteropathogenic
      microorganism, share an ESBL-PB as indirect demonstration of its transmission
      from a common food source. METHODS: From 2003 to 2004 in Barcelona, Spain, stool
      samples from 905 people involved in 132 acute gastroenteritis outbreaks and 226
      food handlers related to the outbreaks were investigated. RESULTS: In 31
      outbreaks, 58 diners carrying one or more ESBL-PB were detected. In 10 outbreaks,
      two or more diners shared the same ESBL-PB, and in four of them, the strain was
      shared with the food handlers. CONCLUSIONS: This study provides circumstantial
      evidence that foods can be a transmission vector for ESBL-PB, probably from two
      reservoirs, food animals and food handlers.

PMID- 18339636
TI  - Changes in metabolic toxicity after switching from stavudine/didanosine to
      tenofovir/lamivudine--a Staccato trial substudy.
AB  - OBJECTIVES: Stavudine is widely used in Thailand and is associated with
      mitochondrial toxicity. Here, we evaluated the effect of switching from
      stavudine/didanosine to tenofovir/lamivudine on measures of metabolic and
      mitochondrial toxicity in Thai patients. METHODS: Thirty-five Thai patients with
      full HIV RNA suppression were switched from stavudine/didanosine to
      tenofovir/lamivudine while receiving saquinavir/ritonavir 1600/100 mg once daily.
      Patients were assessed at the time of switch and 24 and 48 weeks after for
      lipids, liver enzymes, lactate, mitochondrial DNA content and limb/total fat mass
      by dual energy X-ray absorptiometry (DEXA) scanning. RESULTS: Forty-eight weeks
      after the switch, there were significant reductions in lipids and lactate, but no
      change in liver enzymes. There was reversal of lipoatrophy, as shown by rises in
      limb fat mass (+0.38 kg, P = 0.006) and total fat mass (+0.69 kg, P = 0.02) on
      DEXA scan. Patients perceived weight improvement, but did not report reversal of
      lipoatrophy of individual body parts. The mitochondrial DNA/nuclear DNA ratio
      rose (+1.06, P < 0.0001). CONCLUSIONS: After the nucleoside reverse transcriptase
      inhibitor switch, reversal of mitochondrial toxicity was consistent with switch
      studies of mainly Caucasian patients, although the peripheral mononuclear cell
      mitochondrial DNA rise exceeded previous reports.

PMID- 18339637
TI  - Principles of assessing bacterial susceptibility to antibiotics using the agar
      diffusion method.
AB  - OBJECTIVES: The agar diffusion assay is one method for quantifying the ability of
      antibiotics to inhibit bacterial growth. Interpretation of results from this
      assay relies on model-dependent analysis, which is based on the assumption that
      antibiotics diffuse freely in the solid nutrient medium. In many cases, this
      assumption may be incorrect, which leads to significant deviations of the
      predicted behaviour from the experiment and to inaccurate assessment of bacterial
      susceptibility to antibiotics. We sought a theoretical description of the agar
      diffusion assay that takes into consideration loss of antibiotic during diffusion
      and provides higher accuracy of the MIC determined from the assay. METHODS: We
      propose a new theoretical framework for analysis of agar diffusion assays. MIC
      was determined by this technique for a number of antibiotics and analysis was
      carried out using both the existing free diffusion and the new dissipative
      diffusion models. RESULTS: A theory for analysis of antibiotic diffusion in solid
      media is described, in which we consider possible interactions of the test
      antibiotic with the solid medium or partial antibiotic inactivation during
      diffusion. This is particularly relevant to the analysis of diffusion of
      hydrophobic or amphipathic compounds. The model is based on a generalized
      diffusion equation, which includes the existing theory as a special case and
      contains an additional, dissipative term. CONCLUSIONS: Analysis of agar diffusion
      experiments using the new model allows significantly more accurate interpretation
      of experimental results and determination of MICs. The model has more general
      validity and is applicable to analysis of other dissipative processes, for
      example to antigen diffusion and to calculations of substrate load in affinity
      purification.

PMID- 18339638
TI  - ChIPCodis: mining complex regulatory systems in yeast by concurrent enrichment
      analysis of chip-on-chip data.
AB  - MOTIVATION: Eukaryotic genes are often regulated by multiple transcription
      factors (TFs). Depending on the interactions among different TFs the expression
      of a gene can be tuned to respond to diverse environmental conditions. Chip-on
      chip experiments provide a snapshot of which TF are in vivo bound to which genes
      in a particular condition, and have been applied to characterize the regulatory
      code of yeast under several experimental settings. ChIPCodis mines this data to
      provide new insights about how the expression of a particular group of genes is
      regulated. For a given list of yeast genes ChIPCodis determines which
      combinations of TFs are significantly over-represented in a series of
      environmental conditions. AVAILABILITY: http://chipcodis.dacya.ucm.es

PMID- 18339639
TI  - Somatic mosaicism as a basic epileptogenic mechanism?

PMID- 18339640
TI  - Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of
      Alzheimer's disease.
AB  - The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PiB)
      binds with high affinity to beta-pleated sheet aggregates of the amyloid-beta
      (Abeta) peptide in vitro. The in vivo retention of PiB in brains of people with
      Alzheimer's disease shows a regional distribution that is very similar to
      distribution of Abeta deposits observed post-mortem. However, the basis for
      regional variations in PiB binding in vivo, and the extent to which it binds to
      different types of Abeta-containing plaques and tau-containing neurofibrillary
      tangles (NFT), has not been thoroughly investigated. The present study examined
      28 clinically diagnosed and autopsy-confirmed Alzheimer's disease subjects,
      including one Alzheimer's disease subject who had undergone PiB-PET imaging 10
      months prior to death, to evaluate region- and substrate-specific binding of the
      highly fluorescent PiB derivative 6-CN-PiB. These data were then correlated with
      region-matched Abeta plaque load and peptide levels, [(3)H]PiB binding in vitro,
      and in vivo PET retention levels. We found that in Alzheimer's disease brain
      tissue sections, the preponderance of 6-CN-PiB binding is in plaques
      immunoreactive to either Abeta42 or Abeta40, and to vascular Abeta deposits. 6-CN
      PiB labelling was most robust in compact/cored plaques in the prefrontal and
      temporal cortices. While diffuse plaques, including those in caudate nucleus and
      presubiculum, were less prominently labelled, amorphous Abeta plaques in the
      cerebellum were not detectable with 6-CN-PiB. Only a small subset of NFT were 6
      CN-PiB positive; these resembled extracellular 'ghost' NFT. In Alzheimer's
      disease brain tissue homogenates, there was a direct correlation between
      [(3)H]PiB binding and insoluble Abeta peptide levels. In the Alzheimer's disease
      subject who underwent PiB-PET prior to death, in vivo PiB retention levels
      correlated directly with region-matched post-mortem measures of [(3)H]PiB
      binding, insoluble Abeta peptide levels, 6-CN-PiB- and Abeta plaque load, but not
      with measures of NFT. These results demonstrate, in a typical Alzheimer's disease
      brain, that PiB binding is highly selective for insoluble (fibrillar) Abeta
      deposits, and not for neurofibrillary pathology. The strong direct correlation of
      in vivo PiB retention with region-matched quantitative analyses of Abeta plaques
      in the same subject supports the validity of PiB-PET imaging as a method for in
      vivo evaluation of Abeta plaque burden.

PMID- 18339641
TI  - Implications of resolving the diagnosis of PKU for parents and children.
AB  - OBJECTIVE: To examine resolution of the diagnosis among parents of children with
      phenylketonuria (PKU) as a mechanism of adjustment for parents and children.
      METHODS: Reaction to diagnosis interviews were conducted with 52 mothers and 47
      fathers of 55 children with PKU aged 2-12 years. The parents also completed
      questionnaires assessing their personal adjustment (stress symptoms), their
      child's adjustment (behavior problems), and coping variables (personal
      hopefulness and coping strategies). RESULTS: Most mothers (69%) and fathers (77%)
      were resolved to their child's diagnosis. Lower levels of parent stress were
      explained by higher personal hopefulness (14% of the variance for mothers and 21%
      for fathers) and resolution of the diagnosis (15% of the variance for mothers and
      6% for fathers) after taking account of demographic variables and severity of the
      child's PKU. Parent resolution, however, did not contribute independently to the
      variance explained in child behavior problems after taking account of coping
      variables and severity of PKU. CONCLUSIONS: Resolution of the diagnosis of PKU is
      a strong indicator of parent adjustment, and assessment of parent reactions
      should be considered an integral component of clinical care. Further research is
      warranted in relation to the implications of parent resolution for the child's
      response to PKU through different development stages and the effectiveness of
      interventions in aiding parent resolution.

PMID- 18339642
TI  - A strong nucleotypic effect on the cell cycle regardless of ploidy level.
AB  - BACKGROUND AND AIMS: In published studies, positive relationships between
      nucleotype and the duration of the mitotic cell cycle in angiosperms have been
      reported but the highest number of species analyzed was approx. 60. Here an
      analysis is presented of DNA C-values and cell cycle times in root apical
      meristems of angiosperms comprising 110 measurements, including monocots and
      eudicots within a set temperature range, and encompassing an approx. 290-fold
      variation in DNA C-values. METHODS: Data for 110 published cell cycle times of
      seedlings grown at temperatures between 20-25 degrees C were compared with DNA C
      values (58 values for monocots and 52 for eudicots). Regression analyses were
      undertaken for all species, and separately for monocots and eudicots, diploids
      and polyploids, and annuals and perennials. Cell cycle times were plotted against
      the nuclear DNA C-values. KEY RESULTS: A positive relationship was observed
      between DNA C-value and cell cycle time for all species and for eudicots and
      monocots separately, regardless of the presence or absence of polyploid values.
      In this sample, among 52 eudicots the maximum cell cycle length was 18 h, whereas
      the 58 monocot values ranged from 8-120 h. There was a striking additional
      increase in cell cycle duration in perennial monocots with C-values greater than
      25 pg. Indeed, the most powerful relationship between DNA C-value and cell cycle
      time and the widest range of cell cycle times was in perennials regardless of
      ploidy level. CONCLUSIONS: DNA replication is identified as a rate limiting step
      in the cell cycle, the flexibility of DNA replication is explored, and we
      speculate on how the licensing of initiation points of DNA replication may be a
      responsive component of the positive nucleotypic effect of C-value on the
      duration of the mitotic cell cycle.

PMID- 18339643
TI  - Rewatering plants after a long water-deficit treatment reveals that leaf
      epidermal cells retain their ability to expand after the leaf has apparently
      reached its final size.
AB  - BACKGROUND AND AIMS: Leaves expand during a given period of time until they reach
      their final size and form, which is called determinate growth. Duration of leaf
      expansion is stable when expressed in thermal-time and in the absence of stress,
      and consequently it is often proposed that it is controlled by a robust programme
      at the plant scale. The usual hypothesis is that growth cessation occurs when
      cell expansion becomes limited by an irreversible tightening of cell wall, and
      that leaf size is fixed once cell expansion ceases. The objective of this paper
      was to test whether leaf expansion could be restored by rewatering plants after a
      long soil water-deficit period. METHODS: Four experiments were performed on two
      different species (Arabidopsis thaliana and Helianthus annuus) in which the area
      of leaves that had apparently reached their final size was measured upon reversal
      of water stresses of different intensities and durations. KEY RESULTS: Re-growth
      of leaves that had apparently reached their final size occurred in both species,
      and its magnitude depended only on the time elapsed from growth cessation to
      rewatering. Leaf area increased up to 186% in A. thaliana and up to 88% in H.
      annuus after rewatering, with respect to the leaves of plants that remained under
      water deficit. Re-growth was accounted for by cell expansion. Increase in leaf
      area represented actual growth and not only a reversible change due to increased
      turgor. CONCLUSIONS: After the leaf has ceased to grow, leaf cells retain their
      ability to expand for several days before leaf size becomes fixed. A response
      window was identified in both species, during which the extent of leaf area
      recovery decreased with time after the 'initial' leaf growth cessation. These
      results suggest that re-growth after rewatering of leaves having apparently
      attained their final size could be a generalized phenomenon, at least in
      dicotyledonous plants.

PMID- 18339644
TI  - High levels and inflammatory effects of soluble CXC ligand 16 (CXCL16) in
      coronary artery disease: down-regulatory effects of statins.
AB  - AIMS: CXC ligand 16 (CXCL16) may be involved in inflammation and lipid
      metabolism, and we hypothesized a role for this chemokine in coronary artery
      disease (CAD). METHODS AND RESULTS: We performed clinical studies in CAD patients
      as well as experimental studies in cells with relevance to atherogenesis [i.e.
      endothelial cells, vascular smooth muscle cells (SMC), and peripheral blood
      mononuclear cells (PBMC)]. We also examined the ability of HMG-CoA reductase
      inhibitors (statins) to modulate CXCL16 levels both in vivo and in vitro. Our
      main findings were: (i) patients with stable (n = 40) and unstable (n = 40)
      angina had elevated plasma levels of CXCL16 compared with controls (n = 20); (ii)
      low-dose simvastatin (20 mg qd, n = 15) and high-dose atorvastatin (80 mg qd, n =
      9) down-regulated plasma levels of CXCL16 during 6 months of therapy; (iii) in
      vitro, atorvastatin significantly decreased the interleukin (IL)-1beta-mediated
      release of CXCL16 from PBMC and endothelial cells; (iv) attenuating effect of
      atorvastatin on the IL-1beta-mediated release of CXCL16 in PBMC seems to involve
      post-transcriptional modulation as well as down-regulation of CXCL16 release
      through inhibition of the protease a disintegrin and metalloproteinase 10
      (ADAM10); (v) soluble CXCL16 increased the release of IL-8, monocyte
      chemoattractant peptide 1, and matrix metalloproteinases in vascular SMC and
      increased the release of IL-8 and monocyte chemoattractant peptide 1 in PBMC,
      with particularly enhancing effects in cells from CAD patients. CONCLUSION: Our
      findings suggest that soluble CXCL16 could be linked to atherogenesis not only as
      a marker of inflammation, but also as a potential inflammatory mediator.

PMID- 18339645
TI  - Mechanisms of angiogenesis and remodelling of the microvasculature.

PMID- 18339646
TI  - TWIK-related two-pore domain potassium channel TREK-1 in carotid endothelium of
      normotensive and hypertensive mice.
AB  - AIMS: Potassium channels are essential elements of endothelial function.
      Recently, evidence emerged that the TWIK (tandem of P domains in a weak inwardly
      rectifying K+ channel)-related K+ channel (TREK-1) of the two-pore domain
      potassium channel gene family (K2P) may be involved in the regulation of vascular
      tone. However, the functional and molecular characterization of vascular TREK-1
      is incomplete. In this study, we therefore analysed the functional expression of
      TREK-1 in the endothelium. Moreover, we hypothesized that changes in channel
      expression may contribute to altered endothelial vasodilator response under
      conditions of elevated blood pressure. METHODS AND RESULTS: Gene expression and
      function of endothelial TREK-1 were analysed by single-cell RT-PCR, the patch
      clamp technique and pressure myography in murine carotid arteries (CA). K+
      outward currents displaying the characteristics of TREK-1 were observed following
      various TREK-1-activating stimuli such as membrane stretch, intracellular
      acidosis, polyunsaturated fatty acids, isoflurane (ISOFL), riluzole, and
      acetylcholine (ACh). In K(Ca)3.1(-/-) mice exhibiting elevated blood pressure,
      endothelial TREK-1 currents and TREK-1 mRNA expression were enhanced as compared
      with normotensive control mice. TREK-1-mediated vasodilator responses to alpha
      linolenic acid, ISOFL, or ACh were increased. A similar up-regulation of
      endothelial TREK-1 was observed in spontaneously hypertensive rats. CONCLUSION:
      We have found that TREK-1 is an endothelial K+ channel capable of producing
      hyperpolarization and vasodilation. A correlation between hypertension and up
      regulation of TREK-1 was observed in two different animal models of elevated
      blood pressure. Thus, TREK-1 may play a protective role in the cardiovascular
      system by providing a novel type of endothelial hyperpolarization-mediated
      vasodilator response.

PMID- 18339647
TI  - Gender-specific hypertension and responsiveness to nitric oxide in sGCalpha1
      knockout mice.
AB  - AIM: The effects of nitric oxide (NO) in the cardiovascular system are attributed
      in part to cGMP synthesis by the alpha1beta1 isoform of soluble guanylate cyclase
      (sGC). Because available sGC inhibitors are neither enzyme- nor isoform-specific,
      we generated knockout mice for the alpha1 subunit (sGCalpha1(-/-) mice) in order
      to investigate the function of sGCalpha1beta1 in the regulation of blood pressure
      and cardiac function. METHODS AND RESULTS: Blood pressure was evaluated, using
      both non-invasive and invasive haemodynamic techniques, in intact and
      gonadectomized male and female sGCalpha1(-/-) and wild-type (WT) mice. Cardiac
      function was assessed with a conductance catheter inserted in the left ventricle
      of male and female sGCalpha1(-/-) and WT mice. Male sGCalpha1(-/-) mice developed
      hypertension (147 +/- 2 mmHg), whereas female sGCalpha1(-/-) mice did not (115 +/
      2 mmHg). Orchidectomy and treatment with an androgen receptor antagonist
      prevented hypertension, while ovariectomy did not influence the phenotype.
      Chronic testosterone treatment increased blood pressure in ovariectomized
      sGCalpha1(-/-) mice but not in WT mice. The NO synthase inhibitor Nomega-nitro-L
      arginine methyl ester hydrochloride raised blood pressure similarly in male and
      female WT and sGCalpha1(-/-) mice. The ability of NO donor compounds to reduce
      blood pressure was slightly attenuated in sGCalpha1(-/-) male and female mice as
      compared to WT mice. The direct sGC stimulator BAY 41-2272 reduced blood pressure
      only in WT mice. Increased cardiac contractility and arterial elastance as well
      as impaired ventricular relaxation were observed in both male and female
      sGCalpha1(-/-) mice. CONCLUSION: These findings demonstrate that sGCalpha1beta1
      derived cGMP signalling has gender-specific and testosterone-dependent
      cardiovascular effects and reveal that the effects of NO on systemic blood
      pressure do not require sGCalpha1beta1.

PMID- 18339648
TI  - Dual activation of STAT-3 and Akt is required during the trigger phase of
      ischaemic preconditioning.
AB  - AIMS: During preconditioning by tumour necrosis factor-alpha (TNFalpha),
      activation of the signal transducer and activator of transcription-3 (STAT-3) but
      not Akt, is essential, whereas ischaemic cardiac preconditioning (IPC) requires
      both STAT-3 and Akt at the time of reperfusion. However, it is not known whether
      the same signalling pattern occurs during the preconditioning stimulus (trigger
      phase) and whether links exist between STAT-3 and Akt. Hence, our hypothesis is
      that concomitant activation or co-interaction between these two key signals is
      required during the trigger phase for IPC. Conversely, we proposed that there
      would be no such interaction when preconditioning was induced by TNFalpha (TNF
      PC). METHODS AND RESULTS: Cardiomyocytes, isolated from adult wild-type (WT) and
      cardiac-specific STAT-3 knockout (KO) mice, were exposed to simulated ischaemia
      (SI) reperfusion. Cells were preconditioned either by 30 min SI or by 30 min
      TNFalpha (0.5 ng/mL) in the presence or absence of AG490 (100 nM) or wortmannin
      (100 nM) to inhibit STAT-3 or Akt, respectively. Cell viability was evaluated by
      trypan blue, and phosphorylation levels of STAT-3 and Akt were measured by
      Western blot analysis. Similar experiments were conducted in isolated rat hearts
      subjected to an ischaemia-reperfusion insult. Both preconditioning stimuli failed
      to protect KO cardiomyocytes, and addition of AG490 abolished preconditioning in
      WT cardiomyocytes or isolated hearts. Wortmannin abolished the protection
      afforded by IPC, but did not affect TNF-PC in both models. Western blot analysis
      demonstrated that added wortmannin during IPC stimulus decreased STAT-3
      phosphorylation while, conversely, AG490 reduced Akt phosphorylation. CONCLUSION:
      STAT-3 activation could be achieved independent of Akt during TNF-PC. In
      contrast, during an IPC stimulus, both prosurvival signalling molecule cascades
      acted in concert so that inhibiting activation of STAT-3 also inhibited that of
      Akt and vice versa.

PMID- 18339649
TI  - Enhanced acyl-CoA dehydrogenase activity is associated with improved
      mitochondrial and contractile function in heart failure.
AB  - AIMS: Heart failure is associated with decreased myocardial fatty acid oxidation
      capacity and has been likened to energy starvation. Increased fatty acid
      availability results in an induction of genes promoting fatty acid oxidation. The
      aim of the present study was to investigate possible mechanisms by which high fat
      feeding improved mitochondrial and contractile function in heart failure. METHODS
      AND RESULTS: Male Wistar rats underwent coronary artery ligation (HF) or sham
      surgery and were immediately fed either a normal (14% kcal fat) (SHAM, HF) or
      high-fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for 8 weeks.
      Mitochondrial respiration and gene expression and enzyme activities of fatty acid
      regulated mitochondrial genes and proteins were assessed. Subsarcolemmal (SSM)
      and interfibrillar mitochondria were isolated from the left ventricle. State 3
      respiration using lipid substrates octanoylcarnitine and palmitoylcarnitine
      increased in the SSM of HF+FAT compared with SHAM+FAT and HF, respectively (242
      +/- 21, 246 +/- 21 vs. 183 +/- 8, 181 +/- 6 and 193 +/- 17, 185 +/- 16 nAO min(
      1) mg(-1)). Despite decreased medium-chain acyl-CoA dehydrogenase (MCAD) mRNA in
      HF and HF+FAT, MCAD protein was not altered, and MCAD activity increased in
      HF+FAT (HF, 65.1 +/- 2.7 vs. HF+FAT, 81.5 +/- 5.4 nmoles min(-1) mg(-1)).
      Activities of short- and long-chain acyl-CoA dehydrogenase also were elevated and
      correlated to increased state 3 respiration. This was associated with an
      improvement in myocardial contractility as assessed by left ventricular +dP/dt
      max. CONCLUSION: Administration of a high-fat diet increased state 3 respiration
      and acyl-CoA dehydrogenase activities, but did not normalize mRNA or protein
      levels of acyl-CoA dehydrogenases in coronary artery ligation-induced heart
      failure rats.

PMID- 18339650
TI  - Coverage in the National Health Service Breast Screening Programme, 1996-2005:
      correcting for the first invitation of women between 50 and 52 years.
AB  - BACKGROUND: Coverage measures the ability of the National Health Service Breast
      Screening Programme (NHSBSP) to reach the eligible population and has a target of
      70%. OBJECTIVE: To estimate coverage accurately for women aged 50-64. METHODS:
      Routine data from the KC63 return were used to calculate coverage for women aged
      50-64 using an adjusted method that allows for the fact that women receive a
      first invitation to screening between 50 and 52.9 years. RESULTS: The adjusted
      average coverage between 1996 and 2005, for women aged 50-64 was 74.3% and the
      standard unadjusted average measure for the same period was 68.3%. Therefore,
      previous measures of coverage for this age group have underestimated coverage by
      approximately 9% and the adjusted figure is actually well above the target.
      CONCLUSION: In terms of coverage the programme has been performing better than
      previously reported. It is important to monitor the effect of an increasing
      workload on the programmes ability to re-invite women within three years of their
      last screen as maintaining coverage is an important factor in ensuring that the
      NHSBSP is effective in reducing mortality from breast cancer.

PMID- 18339651
TI  - Inheritance of pollen-less anthers and "thrum" and "pin" flowers in periwinkle.
AB  - Two mutants, 1 with small, pollen-less anthers (OR-EA) and another with "pin"
      flowers (EMS 13-2), in contrast to "thrum" flowers found in normal periwinkle
      (Catharanthus roseus) plants, were isolated after induced mutagenesis in strain
      OR and cultivar, "Dhawal," respectively. Inheritance of these 2 traits, pollen
      less anthers, and pin flowers was studied by crossing the mutants with their
      respective parental strains. Segregation ratios observed in F(2) and testcross
      generations of the cross OR-EA x OR suggested that the pollen-less anthers trait
      was determined by duplicate recessive genes. Data obtained from F(2) and F(3)
      generations of the cross involving mutant EMS 13-2 with pin flowers and its
      parental variety Dhawal, suggested that production of pin (mutant) and thrum
      (normal) flowers was under the control of inhibitory epistatic interaction
      between 2 independently inherited genes.

PMID- 18339652
TI  - The ancestral carnivore karyotype (2n = 38) lives today in ringtails.
AB  - Chromosome painting was used to investigate the conservation of high-resolution
      longitudinal 4',6-diamidino-2-phenylindole (DAPI)/G bands in Carnivore
      chromosomes. Cat (Felis catus) and raccoon dog (Nyctereutes procyonoides)
      painting probes were hybridized to the ringtail (Bassaricus astutus), dwarf
      mongoose (Helogale parvula), and Malagasy civet (Fossa fossa) to identify
      homologous chromosome elements. The patterns of chromosome segment homology among
      Carnivore species allowed us to reconstruct and propose the disposition of a high
      resolution banded ancestral carnivore karyotype (ACK). Three bi-armed chromosomes
      consistently found among Caniformia species are represented as 6 homologous
      acrocentric chromosomes among Feliformia species of Carnivora. However,
      reexamination of the most basal of Feliformia species, the African palm civet
      Nandinia, revealed the presence of the 3 heretofore Caniformia bi-armed
      chromosomes. Because these 3 bi-armed chromosomes are found in both Caniformia
      and Feliformia lineages, they are presumed ancestral for all Carnivora,
      suggesting that the ACK chromosome number would be 38, rather than the previously
      supposed 42. Banded chromosomes of the ACK are used to evaluate the consistency
      between recently determined molecular phylogenetic relationships and postulated
      cytogenetic dynamics in the same Carnivore species.

PMID- 18339653
TI  - Altered miRNA repertoire in the simplified chordate, Oikopleura dioica.
AB  - Recent studies reveal correlation between microRNA (miRNA) innovation and
      increased developmental complexity. This is exemplified by dramatic expansion of
      the miRNA inventory in vertebrates, a lineage where genome duplication has played
      a significant evolutionary role. Urochordates, the closest extant group to the
      vertebrates, exhibit an opposite trend to genome and morphological
      simplification. We show that the urochordate, larvacean, Oikopleura dioica,
      possesses the requisite miRNA biogenic machinery. The miRNAs isolated by small
      RNA cloning were expressed throughout the short life cycle, a number of which
      were stocked as maternal determinants prior to rapid embryonic development. We
      identify sex-specific miRNAs that appeared as male/female gonad differentiation
      became apparent and were maintained throughout spermatogenesis. Whereas 80% of
      mammalian miRNAs are hosted in introns of protein-coding genes, the majority of
      O. dioica miRNA loci were located in antisense orientations to such genes.
      Including sister group ascidians in analysis of the urochordate miRNA repertoire,
      we find that 11 highly conserved bilaterian miRNA families have been lost or
      derived to the point they are not recognizable in urochordates and a further 4 of
      these families are absent in larvaceans. Subsequent to this loss/derivation, at
      least 29 novel miRNA families have been acquired in larvaceans. This suggests a
      profound reorganization of the miRNA repertoire integral to evolution in the
      urochordate lineage.

PMID- 18339654
TI  - Vitamin D supplementation in early childhood and risk of type 1 diabetes: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: To assess whether vitamin D supplementation in infancy reduces the
      risk of type 1 diabetes in later life. METHODS: This was a systematic review and
      meta-analysis using Medline, Embase, Cinahl, Cochrane Central Register of
      Controlled Trials and reference lists of retrieved articles. The main outcome
      measure was development of type 1 diabetes. Controlled trials and observational
      studies that had assessed the effect of vitamin D supplementation on risk of
      developing type 1 diabetes were included in the analysis. RESULTS: Five
      observational studies (four case-control studies and one cohort study) met the
      inclusion criteria; no randomised controlled trials were found. Meta-analysis of
      data from the case-control studies showed that the risk of type 1 diabetes was
      significantly reduced in infants who were supplemented with vitamin D compared to
      those who were not supplemented (pooled odds ratio 0.71, 95% CI 0.60 to 0.84).
      The result of the cohort study was in agreement with that of the meta-analysis.
      There was also some evidence of a dose-response effect, with those using higher
      amounts of vitamin D being at lower risk of developing type 1 diabetes. Finally,
      there was a suggestion that the timing of supplementation might also be important
      for the subsequent development of type 1 diabetes. CONCLUSION: Vitamin D
      supplementation in early childhood may offer protection against the development
      of type 1 diabetes. The evidence for this is based on observational studies.
      Adequately powered, randomised controlled trials with long periods of follow-up
      are needed to establish causality and the best formulation, dose, duration and
      period of supplementation.

PMID- 18339655
TI  - Better outcome of schizophrenia in India: a natural selection against severe
      forms?
AB  - Regional variations are observed in outcome of schizophrenia, but reasons remain
      unclear. Outcome of schizophrenia is reported to be better in India. In this
      report based on census data, we highlight substantially greater mortality
      observed among the mentally ill than among the general population during famines
      in India in the 19th century. A possible selection against the most severe forms
      of schizophrenia could account for greater occurrence of better-outcome
      phenotypes. Population histories and environmental influences, including
      epigenetics, need to be considered to further investigate differences between
      schizophrenia phenotypes.

PMID- 18339656
TI  - Perception of discomfort during initial orthodontic tooth alignment using a self
      ligating or conventional bracket system: a randomized clinical trial.
AB  - The aim of this study was to compare the degree of discomfort experienced during
      the period of initial orthodontic tooth movement using Damon3 self-ligating and
      Synthesis conventional ligating pre-adjusted bracket systems. Sixty-two subjects
      were recruited from two centres (32 males and 30 females; mean age 16 years, 3
      months) with lower incisor irregularity between 5 and 12 mm and a prescribed
      extraction pattern, including lower first premolar teeth. These subjects were
      randomly allocated for treatment with either bracket system. Fully ligated Damon3
      0.014-inch Cu NiTi archwires were used for initial alignment in both groups.
      Following archwire insertion, the subjects were given a prepared discomfort diary
      to complete over the first week, recording discomfort by means of a 100 mm visual
      analogue scale at 4 hours, 24 hours, 3 days, and 1 week. The subjects also noted
      any self-prescribed analgesics that were taken during the period of observation.
      Data were analysed using repeated measures analysis of variance. There were no
      statistically significant differences in perceived discomfort levels between the
      two appliances; discomfort did not differ at the first time point and did not
      develop differently across subsequent measurement times. Overall, this
      investigation found no evidence to suggest that Damon3 self-ligating brackets are
      associated with less discomfort than conventional pre-adjusted brackets during
      initial tooth alignment, regardless of age or gender.

PMID- 18339657
TI  - Requirements for the natural killer cell-mediated induction of IgG1 and IgG2a
      expression in B lymphocytes.
AB  - Upon interaction with resting B lymphocytes, IL-2-propagated NK cells can
      initiate the process of Ig constant region switch recombination (CSR) by inducing
      germ line transcripts for gamma2a (Igamma2a) as well as increased levels of mRNA
      for activation-induced cytidine deaminase enzyme. Whereas both these processes
      are necessary for CSR, they are not sufficient because the cells do not proceed
      to the expression of mature mRNA for gamma2a (VDJCgamma2a). In addition, NK cells
      can also upregulate mRNA for the T-box transcription factor (T-bet) in B cells
      without being able to induce further differentiation. Using transgenic B cells
      with B cell receptor specificity for nitrophenol (NP), we have now shown that NP
      Ficoll-stimulated B cells can be induced by NK cells to express IgG2a as well as
      IgG1 presumably due to the completion of the process of switch recombination. The
      inductive ability of NK cells does not require IFN-gamma but does require signals
      transmitted via CD48 by direct cell contact. In addition, NP-Ficoll on its own
      can induce proliferation of antigen-specific B cells as well as germ line
      transcripts of gamma1; however, expression of VDJCgamma1 mRNA also requires NK
      cell interaction with B lymphocytes. Therefore, in the presence of antigen, NK
      cells can provide a necessary signal that substitutes for cytokines in the
      induction of IgG2a as well as IgG1 expression. This in vitro analysis provides a
      mechanistic basis for understanding the documented NK cell effects on T
      independent B cell responses in vivo.

PMID- 18339658
TI  - Estimation of the impact of genital warts on health-related quality of life.
AB  - OBJECTIVES: One of the two new human papillomavirus (HPV) vaccines protects
      against HPV types 6 and 11, which cause over 95% of genital warts, in addition to
      protecting against HPV types 16 and 18. In anticipation of HPV vaccine
      implementation, the impact of genital warts on health-related quality of life
      (HRQoL) was measured to assess the potential benefits of the quadrivalent over
      the bivalent vaccine. METHODS: Genitourinary medicine clinic patients aged 18
      years and older with a current diagnosis of genital warts were eligible; 81
      consented and were interviewed by a member of the research team. A generic HRQoL
      questionnaire, the EQ-5D (comprising EQ-5D index and EQ visual analogue scale
      (VAS) scores) and a disease-specific HRQoL instrument, the CECA10, were
      administered. Previously established UK population norms were used as a control
      group for EQ-5D comparisons. RESULTS: Cases (with genital warts) had lower EQ VAS
      and EQ-5D index scores than controls. After adjusting for age a mean difference
      between cases and controls 30 years of age and under (n = 70) of 13.9 points (95%
      CI 9.9 to 17.6, p<0.001) for the EQ VAS and 0.039 points (95% CI 0.005 to 0.068,
      p = 0.02) on the EQ-5D index (also adjusted for sex) was observed. The difference
      between cases and controls for the EQ VAS was especially notable in young women.
      CONCLUSIONS: Genital warts are associated with a significant detriment to HRQoL.
      The potential added benefit of preventing most cases of genital warts by HPV
      vaccination should be considered in decisions about which HPV vaccine to
      implement in the United Kingdom.

PMID- 18339659
TI  - Men who pay for sex in Spain and condom use: prevalence and correlates in a
      representative sample of the general population.
AB  - OBJECTIVE: To estimate the percentage of men who have paid for heterosexual sex
      in Spain and the percentage who used condoms. To identify the main factors
      associated with these behaviours and to describe opinions about condoms. METHODS:
      Sexual behaviour probability sample survey in men aged 18-49 years resident in
      Spain in 2003 (n = 5153). Computer-assisted face to face and self interview was
      used. Bivariate and multivariate logistic regression analyses were performed.
      RESULTS: 25.4% (n = 1306) of the men had paid for heterosexual sex at some time
      in their lives; 13.3% (n = 687) in the last 5 years and 5.7% (n = 295) in the
      last 12 months. In the logistic analysis this behaviour was associated with older
      age, lower education, being unmarried, foreign birth, being a practicing member
      of a religious group, unsatisfactory communication with parents about sex, age
      under 16 years at first sexual intercourse and having been drunk in the last 30
      days. Of the men who had paid for sex in the previous 5 years, 95% (n = 653) had
      used a condom in the most recent paid contact. In the multivariate analysis, not
      using a condom was associated with age over 30 years and first sexual intercourse
      before age 16 years. Men who did not use condoms in the last commercial
      intercourse had more negative opinions about condoms. CONCLUSIONS: The prevalence
      of paying for heterosexual sex among Spanish men is the highest ever described in
      developed countries. The many variables associated with paying for sex and condom
      use permit the characterisation of male clients of prostitution and should
      facilitate targeting HIV prevention policies.

PMID- 18339660
TI  - Using strain typing to characterise a fluoroquinolone-resistant Neisseria
      gonorrhoeae transmission network in southern California.
AB  - OBJECTIVE: We investigated the initial outbreak of fluoroquinolone-resistant
      Neisseria gonorrhoeae (QRNG) in southern California with analysis of transmission
      using strain typing. METHODS: Surveillance for QRNG was conducted between 2000
      and 2002 in southern California, including epidemiology and strain typing by a
      combination of antibiogram, auxotype, serovar, Lip type and amino acid alteration
      patterns in the quinolone-resistance determining region of GyrA and ParC.
      Combining epidemiological data with strain typing, we describe the emergence of
      QRNG outbreak strains using risk factor analysis and transmission networks.
      RESULTS: Two outbreak strains accounted for 82% of isolates. Both strains
      required proline, were Lip type 17c, had amino acid alterations 91> Phe in GyrA
      and 87> Arg in ParC, but they differed by their serovar, IB-3C8 versus IB-2H7,
      2G2. Outbreak strains were positively associated with men who have sex with men
      (MSM), adjusted odds ratio (AOR) 23.9 (95% confidence interval (CI) 2.2 to 261)
      and negatively associated with travel history: AOR 0.05, (95% CI 0.0 to 0.6).
      Network analysis demonstrated that 17 cases were connected by sexual contacts
      and/or public venues including bars, bathhouses/sex clubs, and internet sites.
      CONCLUSIONS: QRNG may have become established among Californian MSM through an
      identified transmission network of southern Californian bars, bathhouses and
      internet sites.

PMID- 18339661
TI  - Changes in HIV-related behaviours over time and associations with rates of HIV
      related services coverage among female sex workers in Sichuan, China.
AB  - OBJECTIVES: To investigate changes in HIV-related behaviours among female sex
      workers (FSW) and associations with services coverage rates. METHODS: Behavioural
      surveillance data from Sichuan, China, were analysed. A mapping exercise was
      conducted; FSW were recruited from randomly selected sex-work establishments in
      19 sites in Sichuan, China, from 2003 (n = 7068), 2004 (n = 6875) and 2005 (n =
      6833). RESULTS: Site variations were substantial. The random effect pooled AOR
      comparing the prevalence of condom use with regular sex partners, possession of
      condoms, HIV-related knowledge, HIV antibody testing and services coverage rates
      in 2005 versus 2003 ranged from 1.42 to 20.35. The 95% CI of these pooled AOR all
      excluded 1.0; hence rejecting the null hypothesis that such OR were not different
      from 1.0. Most of the AOR of these evaluative parameters (indicator of
      improvement) for the 19 individual sites in 2004 and 2005 (vs 2003) were
      significantly associated with coverage rates (Spearmen correlation coefficients =
      0.35 to 0.67, p<0.05). CONCLUSIONS: Improvements were observed in relevant
      behaviours and coverage rates and the two were associated with each other.

PMID- 18339662
TI  - Inequalities in health by social class dimensions in European countries of
      different political traditions.
AB  - OBJECTIVE: To compare inequalities in self-perceived health in the population
      older than 50 years, in 2004, using Wright's social class dimensions, in nine
      European countries grouped in three political traditions (Social democracy,
      Christian democracy and Late democracies). METHODS: Cross-sectional design,
      including data of the Survey of Health, Ageing and Retirement in Europe (Sweden,
      Denmark, Austria, France, Germany, The Netherlands, Spain, Italy and Greece). The
      population aged from 50 to 74 years was included. Absolute and relative social
      class dimension inequalities in poor self-reported health and long-term illness
      were determined for each sex and political tradition. Relative inequalities were
      assessed by fitting Poisson regression models with robust variance estimators.
      RESULTS: Absolute and relative health inequalities by social class dimensions are
      found in the three political traditions, but these differences are more marked in
      Late democracies and mainly among women. For example the prevalence ratio of poor
      self-perceived health comparing poorly educated women with highly educated women,
      was 1.75 (95% CI: 1.39-2.21) in Late democracies and 1.36 (95% CI: 1.21-1.52) in
      Social democracies. The prevalence differences were 24.2 and 13.7%, respectively.
      CONCLUSION: This study is one of the first to show the impact of different
      political traditions on social class inequalities in health. These results
      emphasize the need to evaluate the impact of the implementation of public
      policies.

PMID- 18339663
TI  - The therapeutic use of osmotic minipumps in the severe combined immunodeficiency
      (SCID) mouse model for rheumatoid arthritis.
AB  - OBJECTIVES: The viral gene transfer of interleukin 1 receptor antagonist (IL1ra)
      and interleukin 10 (IL10) into rheumatoid arthritis (RA) synovial fibroblasts
      (RASFs) has shown protective effects on cartilage destruction in the severe
      combined immunodeficiency (SCID) mouse model of RA. Nevertheless, side effects of
      viral transduction are possible and a number of cytokines or cytokine inhibitors
      are not available encoded in viral vehicles. As the production of viruses coding
      for bioactive proteins is cost and time intensive, we established an in vivo long
      term release model using osmotic minipumps in the SCID mouse model for RA.
      METHODS: Isolated RASFs were cultured for four passages and coimplanted together
      with human cartilage and an Alzet osmotic miniature pump model 2004, containing
      200 microl of IL10 and IL1ra for 40 days in SCID mice. Implants were removed
      after 40 days and evaluated histologically. The actual rates of IL10 and IL1ra in
      murine serum were measured by ELISA. RESULTS: Release of IL10 and IL1ra by the
      pumps was effective as both could be measured in significant amounts in the serum
      of the mice. IL10 and IL1ra release showed protective effects towards the
      coimplanted cartilage, similar to the adenovirally IL10/IL1ra-transduced RASFs.
      The mean (SD) invasion scores for the implants with the osmotic pumps were:
      invasion 0.7 (0.5), degradation 0.5 (0.3) (all parameters significant vs
      controls, p<0.05). CONCLUSIONS: The results demonstrate that the combination of
      osmotic pumps with the SCID mouse model for RA can be used as approach for
      application and evaluation of cartilage-protective molecules. Furthermore, the
      effect of cartilage-protective cytokines is independent of the type of
      application.

PMID- 18339664
TI  - Cortical hand bone loss after 1 year in early rheumatoid arthritis predicts
      radiographic hand joint damage at 5-year and 10-year follow-up.
AB  - OBJECTIVE: To examine 1-year hand bone loss in early rheumatoid arthritis (RA) as
      a predictor of radiographic damage at 5-year and 10-year follow-up METHODS: A
      total of 136 patients with RA (disease duration 0-4 years) were followed for 10
      years with clinical data and hand radiographs. Joint damage was scored according
      to the van der Heijde modification of the Sharp method (vdH Sharp score) and hand
      bone mineral density (BMD) was measured by digital x ray radiogrammetry (DXR).
      Group comparisons, correlation analyses and multivariate analyses were performed
      to evaluate the relationship between hand bone loss and radiographic joint
      damage. RESULTS: Patients with hand BMD loss at 1 year had a higher median
      increase in vdH Sharp score compared to patients without loss at 5 years (12 vs
      2, p = 0.001) and 10 years (22 vs 4, p = 0.002). In a linear regression model
      adjusting for age, gender, baseline C-reactive protein (CRP), anti-cyclic
      citrullinated peptide (CCP), IgM rheumatoid factor (RF) and radiographic damage,
      absolute hand DXR-BMD loss at 1 year was an independent predictor of radiographic
      outcome at 5 years (p<0.01) and 10 years (p = 0.02). In a logistic regression
      model the odds ratio (95% CI) for radiographic progression among patients with
      hand BMD loss was 3.5 (1.4 to 8.8) and 3.5 (1.4 to 8.4) at 5 and 10 years,
      respectively. CONCLUSION: Early hand bone loss measured by DXR-BMD is an
      independent predictor of subsequent radiographic damage. Our findings support
      that quantitative hand bone loss in RA precedes radiographic joint damage and may
      be used as a tool for assessment of bone involvement in RA.

PMID- 18339665
TI  - An international review of projects on hospital performance assessment.
AB  - BACKGROUND: Assessing the quality of health care has become increasingly
      important in health care in response to growing demands from purchasers,
      providers, clinicians and the public. Given the increase in projects and programs
      to assess performance in health care in the last 15 years, the purpose of this
      paper is to review current indicator projects for hospital performance assessment
      and compare them to the Performance Assessment Tool for Quality Improvement in
      Hospitals (PATH), an initiative by the WHO Regional Office for Europe.
      METHODOLOGY: We identified current indicator projects through a systematic
      literature search and through contact with experts. Using an inductive approach
      based on a review of the literature, we identified 10 criteria for the comparison
      of indicator projects. We extracted data and contacted the coordinators of each
      indicator project to validate this information. In addition, we carried out
      interviews with coordinators to gather additional information on the evaluation
      of the respective projects. RESULTS: We included 11 projects that appear to have
      adopted a common methodology for the design and selection of indicators; however,
      major differences exist with regard to the philosophy, scope and coverage of the
      projects. This relates in particular to criteria such as participation,
      disclosure of results and dimensions of hospital performance assessed.
      CONCLUSION: Hospital performance assessment projects have become common
      worldwide, and initiatives such as the WHO PATH project need to be well
      coordinated with existing projects. Our review raised questions regarding the
      impact of hospital performance assessment that should be pursued in further
      research.

PMID- 18339666
TI  - Health sector accreditation research: a systematic review.
AB  - PURPOSE: The purpose of this study was to identify and analyze research into
      accreditation and accreditation processes. DATA SOURCES: A multi-method,
      systematic review of the accreditation literature was conducted from March to May
      2007. The search identified articles researching accreditation. Discussion or
      commentary pieces were excluded. STUDY SELECTION: From the initial identification
      of over 3000 abstracts, 66 studies that met the search criteria by empirically
      examining accreditation were selected. DATA EXTRACTION AND RESULTS OF DATA
      SYNTHESIS: The 66 studies were retrieved and analyzed. The results, examining the
      impact or effectiveness of accreditation, were classified into 10 categories:
      professions' attitudes to accreditation, promote change, organizational impact,
      financial impact, quality measures, program assessment, consumer views or patient
      satisfaction, public disclosure, professional development and surveyor issues.
      RESULTS: The analysis reveals a complex picture. In two categories consistent
      findings were recorded: promote change and professional development. Inconsistent
      findings were identified in five categories: professions' attitudes to
      accreditation, organizational impact, financial impact, quality measures and
      program assessment. The remaining three categories-consumer views or patient
      satisfaction, public disclosure and surveyor issues-did not have sufficient
      studies to draw any conclusion. The search identified a number of national health
      care accreditation organizations engaged in research activities. CONCLUSION: The
      health care accreditation industry appears to be purposefully moving towards
      constructing the evidence to ground our understanding of accreditation.

PMID- 18339667
TI  - Detection and prevention of medication misadventures in general practice.
AB  - BACKGROUND: Adverse drug events are leading categories of iatrogenic patient
      injury. Development of preventive strategies for general practice setting depends
      on effective detection of events. OBJECTIVE: The aim of the study is to compare
      the strengths and weaknesses of voluntary reporting, chart review and patient
      survey in measuring medication misadventures in general practice and to analyze
      the events by severity and preventability, drug groups and patients' and doctors'
      characteristics, for the formulation of preventive strategies. METHOD: In the 2
      month study period, we applied voluntary report, chart review and patient survey
      to collect data related to medication misadventures and compared their detection
      rate. RESULTS: The chart review demonstrated the highest yield for detecting
      overall medication misadventures (2.03% medication orders), followed by patient
      survey (1.46% medication orders) and voluntary reporting (0.52% medication
      orders). Chart review and patient survey were better than voluntary reporting in
      uncovering preventable adverse drug events. However, voluntary reporting was
      pivotal in capturing sentinel events. Beta-blocker, diuretic, angiotensin
      converting enzyme inhibitor, aspirin and non-steroidal anti-inflammatory drugs
      had caused 82.0% of all adverse drug events. These events were more common with
      advanced age of patients, greater number of consultation problems and prescribed
      drug items. Additional resources implicated were minimal. CONCLUSION: We
      suggested a complementary approach using chart review and voluntary reporting in
      measuring and monitoring medication misadventures in general practice. Close
      monitoring of the events was necessary for older patients, multiple medical
      problems and poly-pharmacy and for patients using beta-blocker, diuretic,
      angiotensin-converting enzyme inhibitor, aspirin or non-steroidal anti
      inflammatory drugs on a long-term basis.

PMID- 18339668
TI  - Psychometric evaluation of the European Organization for Research and Treatment
      of Cancer in-patient satisfaction with care questionnaire ('Sinhala' version) for
      use in a South-Asian setting.
AB  - BACKGROUND: Patients' satisfaction with cancer care has not been studied in
      detail in the South-Asian region in spite of rising cancer incidence. OBJECTIVE:
      To validate the 'Sinhala' translation of the European Organization for Research
      and Treatment of Cancer (EORTC) in-patient satisfaction with care questionnaire
      (IN-PATSAT32) in Sri Lanka. METHOD: We administered the translated version of the
      IN-PATSAT32 on 343 newly diagnosed adult in-patients with cancers of head and
      neck, breast, oesophagus, cervix uteri and lung, recruited from seven tertiary
      care oncology treatment centres in the District of Colombo. Patients with
      previous cancer diagnoses, too frail/mentally unfit, with evidence of brain
      metastases and unable/unwilling to give informed consent were excluded.
      Psychometric testing assessed the hypothesized scale structure, scale
      reliability, construct validity and acceptability of the IN-PATSAT32. RESULTS: A
      high response rate (100%) and low missing data (0.05%) confirmed the
      acceptability of the IN-PATSAT32. The hypothesized scale structure was confirmed
      with 100% item-convergent and 98.6% item-discriminant validity, and a scaling
      success rate, defined as items correlating significantly higher (more than 1.96
      standard errors) with its own scale (corrected for overlap) than with another
      scale, of 97.9%. The Cronbach's alpha coefficient for internal consistency
      exceeded 0.70 in all scales. Construct validity was confirmed with inter-scale
      correlations, which were all statistically significant (P<0.01) and were of
      moderate-to-high magnitude, evidence that they were measuring distinct dimensions
      of patient satisfaction. CONCLUSION: The translated version of the IN-PATSAT32
      has proved to be a reliable and valid measure of satisfaction with cancer care in
      patients with heterogeneous cancer diagnoses in Sri Lanka.

PMID- 18339669
TI  - Analyzing the functions of large glycoconjugates through the dissipative
      properties of their absorbed layers using the gel-forming mucin MUC5B as an
      example.
AB  - Glyconjugates such as mucins, proteoglycans, and polysaccharides form the
      structural basis of protective cell-surface layers. In particular gel-forming
      mucins define a zone between the epithelial cell layer and the environment. Such
      molecules are of extreme molecular weight 5-100 x 10(6) and size (Rg 20-300 nm).
      On this account their biochemistry is inseparable from their physical
      biochemistry. Combining laser light scattering and quartz crystal mass balance
      with dissipation methods (QCM-D) we have investigated the properties of the MUC5B
      mucin and its cognate fragments when bound to a hydrophobic surface. MUC5B forms
      the basis of gels responsible for the protection of the oral cavity, lung, and
      cervical canal surfaces. Here we show, by analyzing dissipative interactions of
      hydrophobic, gold, and polystyrene surfaces, with the intact MUC5B molecule, its
      reduced subunits, and glycosylated tryptic fragments (obtained after reduction),
      the formation of 40- to 100-nm-thick highly structured, hydrated interfaces.
      These interfaces are dominated in their geometry and dissipative properties by
      the negatively charged carbohydrate-rich domains of the molecule, the naked
      protein domains being responsible for attachment. These carbohydrate-rich
      surfaces have well-defined absorptive properties and permit the entry and
      entrapment of albumin-coated micro-beads into the absorbed layer at and below a
      size of 60 nm. However beads larger than 100 nm are completely excluded from the
      surfaces. These absorptive phenomena correlate with large changes in film
      dissipation and thus may not only be important in biological functions, e.g.
      binding viruses, but could also be informative to the surfaces (often ciliated)
      onto which such mucus films are attached.

PMID- 18339670
TI  - Direct interaction of AGL24 and SOC1 integrates flowering signals in Arabidopsis.
AB  - During the transition from vegetative to reproductive growth, the shoot meristem
      of flowering plants acquires the inflorescence identity to generate flowers
      rather than vegetative tissues. An important regulator that promotes the
      inflorescence identity in Arabidopsis is AGAMOUS-LIKE 24 (AGL24), a MADS-box
      transcription factor. Using a functional estradiol-inducible system in
      combination with microarray analysis, we identified AGL24-induced genes,
      including SUPPRESSOR OF OVEREXPRESSION OF CO 1 (SOC1), a floral pathway
      integrator. Chromatin immunoprecipitation (ChIP) analysis of a functional AGL24
      6HA-tagged line revealed in vivo binding of AGL24-6HA to the regulatory region of
      SOC1. Mutagenesis of the AGL24 binding site in the SOC1 promoter decreased
      Pro(SOC1):GUS expression and compromised SOC1 function in promoting flowering.
      Our results show that SOC1 is one of the direct targets of AGL24, and that SOC1
      expression is upregulated by AGL24 at the shoot apex at the floral transitional
      stage. ChIP assay using a functional SOC1-9myc-tagged line and promoter
      mutagenesis analysis also revealed in vivo binding of SOC1-9myc to the regulatory
      regions of AGL24 and upregulation of AGL24 at the shoot apex by SOC1.
      Furthermore, we found that as in other flowering genetic pathways, the effect of
      gibberellins on flowering under short-day conditions was mediated by the
      interaction between AGL24 and SOC1. These observations suggest that during floral
      transition, a positive-feedback loop conferred by direct transcriptional
      regulation between AGL24 and SOC1 at the shoot apex integrates flowering signals.

PMID- 18339671
TI  - Shroom3-mediated recruitment of Rho kinases to the apical cell junctions
      regulates epithelial and neuroepithelial planar remodeling.
AB  - Remodeling of epithelial sheets plays important roles in animal morphogenesis.
      Shroom3 is known to regulate the apical constriction of epithelial cells. Here,
      we show that Shroom3 binds ROCKs and recruits them to the epithelial apical
      junctions. We identified the Shroom3-binding site (RII-C1) on ROCKs, and found
      that RII-C1 could antagonize the Shroom3-ROCK interaction, interfering with the
      action of Shroom3 on cell morphology. In the invaginating neural plate/tube,
      Shroom3 colocalized with ROCKs at the apical junctions; Shroom3 depletion or RII
      C1 expression in the tube removed these apically localized ROCKs, and
      concomitantly blocked neural tube closure. Closing neural plate exhibited
      peculiar cell assemblies, including rosette formation, as well as a planar
      polarized distribution of phosphorylated myosin regulatory light chain, but these
      were abolished by ROCK inhibition or RII-C1 expression. These results demonstrate
      that the Shroom3-ROCK interaction is crucial for the regulation of epithelial and
      neuroepithelial cell arrangement and remodeling.

PMID- 18339672
TI  - Drosophila optic lobe neuroblasts triggered by a wave of proneural gene
      expression that is negatively regulated by JAK/STAT.
AB  - Neural stem cells called neuroblasts (NBs) generate a variety of neuronal and
      glial cells in the central nervous system of the Drosophila embryo. These NBs,
      few in number, are selected from a field of neuroepithelial (NE) cells. In the
      optic lobe of the third instar larva, all NE cells of the outer optic anlage
      (OOA) develop into either NBs that generate the medulla neurons or lamina neuron
      precursors of the adult visual system. The number of lamina and medulla neurons
      must be precisely regulated because photoreceptor neurons project their axons
      directly to corresponding lamina or medulla neurons. Here, we show that
      expression of the proneural protein Lethal of scute [L(1)sc] signals the
      transition of NE cells to NBs in the OOA. L(1)sc expression is transient,
      progressing in a synchronized and ordered ;proneural wave' that sweeps toward
      more lateral NEs. l(1)sc expression is sufficient to induce NBs and is necessary
      for timely onset of NB differentiation. Thus, proneural wave precedes and induces
      transition of NE cells to NBs. Unpaired (Upd), the ligand for the JAK/STAT
      signaling pathway, is expressed in the most lateral NE cells. JAK/STAT signaling
      negatively regulates proneural wave progression and controls the number of NBs in
      the optic lobe. Our findings suggest that NBs might be balanced with the number
      of lamina neurons by JAK/STAT regulation of proneural wave progression, thereby
      providing the developmental basis for the formation of a precise topographic map
      in the visual center.

PMID- 18339673
TI  - Life-cycle-generation-specific developmental processes are modified in the
      immediate upright mutant of the brown alga Ectocarpus siliculosus.
AB  - Development of the sporophyte and gametophyte generations of the brown alga E.
      siliculosus involves two different patterns of early development, which begin
      with either a symmetric or an asymmetric division of the initial cell,
      respectively. A mutant, immediate upright (imm), was isolated that exhibited
      several characteristics typical of the gametophyte during the early development
      of the sporophyte generation. Genetic analyses showed that imm is a recessive,
      single-locus Mendelian factor and analysis of gene expression in this mutant
      indicated that the regulation of a number of life-cycle-regulated genes is
      specifically modified in imm mutant sporophytes. Thus, IMM appears to be a
      regulatory locus that controls part of the sporophyte-specific developmental
      programme, the mutant exhibiting partial homeotic conversion of the sporophyte
      into the gametophyte, a phenomenon that has not been described previously.

PMID- 18339674
TI  - NKX2.1 specifies cortical interneuron fate by activating Lhx6.
AB  - In the ventral telencephalon, the medial ganglionic eminence (MGE) is a major
      source of cortical interneurons. Expression of the transcription factor NKX2.1 in
      the MGE is required for the specification of two major subgroups of cortical
      interneurons - those that express parvalbumin (PV) or somatostatin (SST) - but
      direct targets of NKX2.1 remain to be established. We find that electroporation
      of Nkx2.1 cDNA into the ventral telencephalon of slice cultures from Nkx2.1-/-
      mouse embryos, followed by transplantation into neonatal cortex to permit
      postnatal analysis of their fate, rescues the loss of PV- and SST-expressing
      cells. The LIM-homeobox gene Lhx6 is induced by this rescue experiment, and gain-
      and loss-of-function studies suggest that Lhx6 is necessary and sufficient to
      rescue these and other interneuron phenotypes in cells transplanted from Nkx2.1-/
      slices. Finally, NKX2.1 protein binds a highly conserved sequence in the Lhx6
      promoter, and this sequence appears to mediate the direct activation of Lhx6 by
      NKX2.1. The slice transfection and transplantation methods employed here are
      beginning to uncover embryonic mechanisms for specifying neuronal fates that only
      become definable postnatally.

PMID- 18339675
TI  - Polycomb group proteins Ring1A/B are functionally linked to the core
      transcriptional regulatory circuitry to maintain ES cell identity.
AB  - The Polycomb group (PcG) proteins mediate heritable silencing of developmental
      regulators in metazoans, participating in one of two distinct multimeric protein
      complexes, the Polycomb repressive complexes 1 (PRC1) and 2 (PRC2). Although PRC2
      has been shown to share target genes with the core transcription network,
      including Oct3/4, to maintain embryonic stem (ES) cells, it is still unclear
      whether PcG proteins and the core transcription network are functionally linked.
      Here, we identify an essential role for the core PRC1 components Ring1A/B in
      repressing developmental regulators in mouse ES cells and, thereby, in
      maintaining ES cell identity. A significant proportion of the PRC1 target genes
      are also repressed by Oct3/4. We demonstrate that engagement of PRC1 at target
      genes is Oct3/4-dependent, whereas engagement of Oct3/4 is PRC1-independent.
      Moreover, upon differentiation induced by Gata6 expression, most of the Ring1A/B
      target genes are derepressed and the binding of Ring1A/B to their target loci is
      also decreased. Collectively, these results indicate that Ring1A/B-mediated
      Polycomb silencing functions downstream of the core transcriptional regulatory
      circuitry to maintain ES cell identity.

PMID- 18339676
TI  - A core cochlear phenotype in USH1 mouse mutants implicates fibrous links of the
      hair bundle in its cohesion, orientation and differential growth.
AB  - The planar polarity and staircase-like pattern of the hair bundle are essential
      to the mechanoelectrical transduction function of inner ear sensory cells.
      Mutations in genes encoding myosin VIIa, harmonin, cadherin 23, protocadherin 15
      or sans cause Usher syndrome type I (USH1, characterized by congenital deafness,
      vestibular dysfunction and retinitis pigmentosa leading to blindness) in humans
      and hair bundle disorganization in mice. Whether the USH1 proteins are involved
      in common hair bundle morphogenetic processes is unknown. Here, we show that
      mouse models for the five USH1 genetic forms share hair bundle morphological
      defects. Hair bundle fragmentation and misorientation (25-52 degrees mean
      kinociliary deviation, depending on the mutant) were detected as early as
      embryonic day 17. Abnormal differential elongation of stereocilia rows occurred
      in the first postnatal days. In the emerging hair bundles, myosin VIIa, the actin
      binding submembrane protein harmonin-b, and the interstereocilia-kinocilium
      lateral link components cadherin 23 and protocadherin 15, all concentrated at
      stereocilia tips, in accordance with their known in vitro interactions. Soon
      after birth, harmonin-b switched from the tip of the stereocilia to the upper end
      of the tip link, which also comprises cadherin 23 and protocadherin 15. This
      positional change did not occur in mice deficient for cadherin 23 or
      protocadherin 15. We suggest that tension forces applied to the early lateral
      links and to the tip link, both of which can be anchored to actin filaments via
      harmonin-b, play a key role in hair bundle cohesion and proper orientation for
      the former, and in stereociliary elongation for the latter.

PMID- 18339677
TI  - The BLADE-ON-PETIOLE genes are essential for abscission zone formation in
      Arabidopsis.
AB  - The Arabidopsis BLADE-ON-PETIOLE 1 (BOP1) and BOP2 genes encode redundant
      transcription factors that promote morphological asymmetry during leaf and floral
      development. Loss-of-function bop1 bop2 mutants display a range of developmental
      defects, including a loss of floral organ abscission. Abscission occurs along
      specialised cell files, called abscission zones (AZs) that develop at the
      junction between the leaving organ and main plant body. We have characterized the
      bop1 bop2 abscission phenotype to determine how BOP1 and BOP2 contribute to the
      known abscission developmental framework. Histological analysis and petal
      breakstrength measurements of bop1 bop2 flowers show no differentiation of floral
      AZs. Furthermore, vestigial cauline leaf AZs are also undifferentiated in bop1
      bop2 mutants, suggesting that BOP proteins are essential to establish AZ cells in
      different tissues. In support of this hypothesis, BOP1/BOP2 activity is required
      for both premature floral organ abscission and the ectopic abscission of cauline
      leaves promoted by the INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) gene under the
      control of the constitutive CaMV 35S promoter. Expression of several abscission
      related marker genes, including IDA, is relatively unperturbed in bop1 bop2
      mutants, indicating that these AZ genes respond to positional cues that are
      independent of BOP1/BOP2 activity. We also show that BOP1 and BOP2 promote growth
      of nectary glands, which normally develop at the receptacle adjacent to
      developing AZs. Taken together, these data suggest that BOP1/BOP2 activity is
      required for multiple cell differentiation events in the proximal regions of
      inflorescence lateral organs.

PMID- 18339678
TI  - The stepwise specification of embryonic stem cells to hematopoietic fate is
      driven by sequential exposure to Bmp4, activin A, bFGF and VEGF.
AB  - The differentiation of embryonic stem (ES) cells offers a powerful approach to
      study mechanisms implicated in cell fate decision. A major hurdle, however, is to
      promote the directed and efficient differentiation of ES cells toward a specific
      lineage. Here, we define in serum-free media the minimal factor requirement
      controlling each step of the differentiation process, resulting in the production
      of highly enriched hematopoietic progenitors. Four factors - Bmp4, activin A,
      bFGF (Fgf2) and VEGF (VegfA) - are sufficient to drive the selective and
      efficient differentiation of mouse ES cells to hematopoiesis. Each of these
      factors appears to regulate a step of the process: Bmp4 promotes the very
      efficient formation of mesoderm; bFGF and activin A induce the differentiation of
      these mesodermal precursors to the hemangioblast fate; and VEGF is required for
      the production of fully committed hematopoietic progenitors. The stimulation of
      mesodermal precursors by bFGF and activin A switches on very rapidly the
      hematopoietic program, allowing us to dissect the molecular events leading to the
      formation of the hemangioblast. Runx1, Scl (Tal1) and Hhex expression is
      upregulated within 3 hours of stimulation, whereas upregulation of Lmo2 and Fli1
      is observed later. Interestingly, increased expression levels of genes such as
      cMyb, Pu.1 (Sfpi1), Gata1 and Gata2 are not observed at the onset of
      hemangioblast commitment. This stepwise control of differentiation is extremely
      efficient, giving rise to a very high frequency of hematopoietic precursors, and
      provides an optimal system for understanding the molecular machineries involved
      in blood progenitor commitment.

PMID- 18339679
TI  - Randomised aspirin assignment and risk of adult-onset asthma in the Women's
      Health Study.
AB  - BACKGROUND: Randomised data in men show a small but significant reduction in the
      risk of adult-onset asthma among those given aspirin. The results from an
      observational study in women suggest that frequent use of aspirin decreases the
      risk of adult-onset asthma, but randomised data in women are lacking. A study was
      undertaken to test the effect of 100 mg aspirin or placebo on alternate days on
      the risk of adult-onset asthma in the Women's Health Study. METHODS: A
      randomised, double-blind, placebo-controlled clinical trial of aspirin and
      vitamin E was performed in apparently healthy women with no indication or
      contraindication to aspirin therapy and no history of asthma at study entry.
      Female health professionals self-reported an asthma diagnosis on yearly
      questionnaires. RESULTS: Among 37 270 women with no reported history of asthma
      prior to randomisation and during 10 years of follow-up, there were 872 new cases
      diagnosed with asthma in the aspirin group and 963 in the placebo group (hazard
      ratio 0.90; 95% CI 0.82 to 0.99; p = 0.027). This apparent 10% lower relative
      risk of incident adult-onset asthma among those assigned to aspirin was
      significantly modified by body mass index, with no effect in women with a body
      mass index of >/=30 kg/m2. The effect of aspirin on adult-onset asthma was not
      significantly modified by age, smoking status, exercise levels, postmenopausal
      hormone use or randomised vitamin E assignment. CONCLUSIONS: In this large
      randomised clinical trial of apparently healthy adult women, administration of
      100 mg aspirin on alternate days reduced the relative risk of a newly reported
      diagnosis of asthma.

PMID- 18339680
TI  - Associations of dietary methyl donor intake with MLH1 promoter hypermethylation
      and related molecular phenotypes in sporadic colorectal cancer.
AB  - Intake of dietary factors that serve as methyl group donors may influence
      promoter hypermethylation in colorectal carcinogenesis. We investigated whether
      dietary folate, vitamin B2 and vitamin B6, methionine and alcohol were associated
      with mutL homologue 1 (MLH1) hypermethylation and the related molecular
      phenotypes of MLH1 protein expression, microsatellite instability (MSI) and BRAF
      mutations in patients with colorectal carcinomas. Within the Netherlands Cohort
      Study on diet and cancer (n = 120 852), 648 cases (367 men and 281 women) and
      4059 subcohort members were available for data analyses from a follow-up period
      between 2.3 and 7.3 years after baseline. Gender-specific adjusted incidence rate
      ratios (RRs) were calculated over categories of dietary intake in case-cohort
      analyses. The intakes of folate, vitamin B2, methionine and alcohol were not
      associated with risk of tumors showing MLH1 hypermethylation, those lacking MLH1
      protein expression or with MSI. Among men, we observed strong positive
      associations between folate and BRAF-mutated tumors (RR = 3.04 for the highest
      versus lowest tertile of intake, P(trend) = 0.03) and between vitamin B6 and
      tumors showing MLH1 hypermethylation (highest versus lowest tertile: RR = 3.23,
      P(trend) = 0.03). Among women, the relative risks of tumors with BRAF mutations
      or MLH1 hypermethylation were also increased in the highest tertiles of folate
      and vitamin B6 intake, respectively, but these did not reach statistical
      significance. The positive associations between folate intake and tumors
      harboring BRAF mutations and between vitamin B6 intake and those showing MLH1
      hypermethylation were most pronounced among men and may suggest that these
      vitamins enhance colorectal cancer risk through genetic as well as epigenetic
      aberrations.

PMID- 18339681
TI  - Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric
      cancer in Japan: a nested case-control study.
AB  - Fruits and vegetables have been suggested to confer protection against diseases
      such as cancer through the effects of antioxidants, often represented by
      carotenoids. We investigated the impact of carotenoids, retinol and tocopherol on
      gastric cancer development in a large nested case-control study among Japanese
      with known Helicobacter pylori infection status. A total of 36 745 subjects aged
      40-69 in the Japan Public Health Center-based Prospective Study who responded to
      the baseline questionnaire and provided blood samples in 1990-1995 were followed
      until 2004. Plasma levels of carotenoids in 511 gastric cancer cases and 511
      matched controls were measured by high-performance liquid chromatography. Odds
      ratios (ORs) and their corresponding 95% confidence intervals (CIs) were
      estimated using conditional logistic regression models. Plasma level of beta
      carotene was inversely associated with the risk of gastric cancer (compared with
      the lowest quartile: OR = 0.63, 95% CI = 0.31-0.75; OR = 0.48, 95% CI = 0.31-0.75
      and OR = 0.46, 95% CI = 0.28-0.75, for quartile 2, 3 and 4, respectively,
      P(trend) < 0.01). Inverse associations were evident in men for alpha-carotene
      (P(trend) = 0.04) and beta-carotene (P(trend) < 0.01), but not in women, who had
      relatively higher plasma levels compared with men. We found no statistically
      significant association between plasma levels of lutein/zeaxanthin, lycopene,
      retinol, alpha- or gamma-tocopherol and gastric cancer risk. Our findings suggest
      that those who have very low plasma levels of alpha-carotene and beta-carotene
      are at a higher risk of gastric cancer.

PMID- 18339682
TI  - Maternal and offspring genetic variants of AKR1C3 and the risk of childhood
      leukemia.
AB  - The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a
      regulator of myeloid cell proliferation and differentiation, represents an
      important candidate gene for studying human carcinogenesis. In a prospectively
      enrolled population-based case-control study of Han Chinese conducted in
      Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls <20
      years old were recruited between November 1997 and December 2005. The present
      study set out to evaluate the association between childhood leukemia and both
      maternal and offspring's genotypes. To do so, we conducted a systematic
      assessment of common single-nucleotide polymorphisms (SNPs) at the 5' flanking 10
      kb to 3' UTR of AKR1C3 gene. Gln5His and three tagSNPs (rs2245191, rs10508293 and
      rs3209896) and one multimarker (rs2245191, rs10508293 and rs3209896) were
      selected with average 90% coverage of untagged SNPs by using the HapMap II data
      set. Odds ratios and 95% confidence intervals were adjusted for age and gender.
      After correcting for multiple comparisons, we observed that risk of developing
      childhood leukemia is significantly associated with rs10508293 polymorphism on
      intron 4 of the AKR1C3 gene in both offspring alone and in the combined maternal
      and offspring genotypes (nominal P < 0.0001, permutation P < 0.005). The maternal
      methylenetetrahydrofolate reductase A1298C polymorphism was found to be an effect
      modifier of the maternal intron 4 polymorphism of the AKR1C3 gene (rs10508293)
      and the childhood leukemia risk. In conclusion, this study suggests that AKR1C3
      polymorphisms may be important predictive markers for childhood leukemia
      susceptibility.

PMID- 18339683
TI  - Delphinidin, a dietary anthocyanidin, inhibits platelet-derived growth factor
      ligand/receptor (PDGF/PDGFR) signaling.
AB  - Most cancers are dependent on the growth of tumor blood vessels and inhibition of
      tumor angiogenesis may thus provide an efficient strategy to retard or block
      tumor growth. Recently, tumor vascular targeting has expanded to include not only
      endothelial cells (ECs) but also smooth muscle cells (SMCs), which contribute to
      a mature and functional vasculature. We have reported previously that
      delphinidin, a major biologically active constituent of berries, inhibits the
      vascular endothelial growth factor-induced phosphorylation of vascular
      endothelial growth factor receptor-2 and blocks angiogenesis in vitro and in
      vivo. In the present study, we show that delphinidin also inhibits activation of
      the platelet-derived growth factor (PDGF)-BB receptor-beta [platelet-derived
      growth factor receptor-beta (PDGFR-beta)] in SMC and that this inhibition may
      contribute to its antitumor effect. The inhibitory effect of delphinidin on PDGFR
      beta was very rapid and led to the inhibition of PDGF-BB-induced activation of
      extracellular signal-regulated kinase (ERK)-1/2 signaling and of the chemotactic
      motility of SMC, as well as the differentiation and stabilization of EC and SMC
      into capillary-like tubular structures in a three-dimensional coculture system.
      Using an anthocyan-rich extract of berries, we show that berry extracts were able
      to suppress the synergistic induction of vessel formation by basic fibroblast
      growth factor-2 and PDGF-BB in the mouse Matrigel plug assay. Oral administration
      of the berry extract also significantly retarded tumor growth in a lung carcinoma
      xenograft model. Taken together, these results provide new insight into the
      molecular mechanisms underlying the antiangiogenic activity of delphinidin that
      will be helpful for the development of dietary-based chemopreventive strategies.

PMID- 18339684
TI  - Aberrations of chromosome 19 in asbestos-associated lung cancer and in asbestos
      induced micronuclei of bronchial epithelial cells in vitro.
AB  - Exposure to asbestos is known to induce lung cancer, and our previous studies
      have suggested that specific chromosomal regions, such as 19p13, are
      preferentially aberrant in lung tumours of asbestos-exposed patients. Here, we
      further examined the association between the 19p region and exposure to asbestos
      using array comparative genomic hybridization and fluorescence in situ
      hybridization (FISH) in lung tumours and FISH characterization of asbestos
      induced micronuclei (MN) in human bronchial epithelial BEAS 2B cells in vitro. We
      detected an increased number of 19p losses in the tumours of asbestos-exposed
      patients in comparison with tumours from non-exposed subjects with similar
      distribution of tumour histology in both groups (13/33; 39% versus 3/25; 12%, P =
      0.04). In BEAS 2B cells, a 48 h exposure to crocidolite asbestos (2.0
      microg/cm(2)) was found to induce centromere-negative MN-harbouring chromosomal
      fragments. Furthermore, an increased frequency of rare MN containing a 19p
      fragment was observed after the crocidolite treatment in comparison with
      untreated controls (6/6000 versus 1/10 000, P = 0.01). The results suggest that
      19p has significance in asbestos-associated carcinogenesis and that asbestos may
      be capable of inducing specific chromosome aberrations.

PMID- 18339685
TI  - Hypoxia-inducible factor (HIF)-1 alpha directly enhances the transcriptional
      activity of stem cell factor (SCF) in response to hypoxia and epidermal growth
      factor (EGF).
AB  - Stem cell factor (SCF) plays important roles in tumor growth and angiogenesis.
      However, its regulatory mechanism remains largely undefined. Here, we report that
      hypoxia upregulated the expression of SCF in MCF-7 breast cancer cells in both
      messenger RNA and protein levels. When hypoxia-inducible factor (HIF)-1 alpha
      expression was knocked down by RNA interference, the MCF-7 cell expression of SCF
      was decreased significantly. Furthermore, the SCF receptor, c-kit phosphorylation
      was significantly strengthened by the condition culture media from hypoxic MCF-7
      and MCF-7-c cells. The survival of A549 cells was more dependent on SCF under
      hypoxia. Analysis of SCF promoter 5'-flanking region revealed a potential hypoxia
      response element (HRE; 5'-GCGTG-3') located at -68 to -64 relative to the
      transcriptional start site. Chromatin immunoprecipitation assay demonstrated that
      HIF-1 alpha directly bound to this region under normoxia, and this binding
      activity was significantly enhanced under hypoxia. Overexpression of HIF-1 alpha
      significantly upregulated the expression of luciferase reporter gene under
      control of the SCF promoters in both MCF-7 cells and human embryonic kidney 293
      cells, but mutation of the HRE site completely blocked this effect. Epidermal
      growth factor was also able to enhance the SCF expression under normoxia in MCF-7
      cells, which was dependent on HIF-1 alpha. Taken together, our data demonstrated
      that HIF-1 alpha was a key regulator of SCF expression in breast cancer cells.
      Hypoxia and epidermal growth factor receptor signal coexisted in the tumor
      microenvironment and might promote angiogenesis through HIF-1 alpha-mediated
      upregulation of SCF and other angiogenic factors.

PMID- 18339686
TI  - t10,c12-Conjugated linoleic acid stimulates mammary tumor progression in
      Her2/ErbB2 mice through activation of both proliferative and survival pathways.
AB  - The t10,c12 isomer of conjugated linoleic acid (CLA) inhibits rat mammary
      carcinogenesis, metastasis from a transplantable mouse mammary tumor and
      angiogenesis; however, it stimulates mammary tumorigenesis in transgenic mice
      overexpressing ErbB2 in the mammary epithelium (ErbB2 transgenic mice). In the
      current study, we report that a 4-week supplementation of the diet with 0.5%
      trans-10, cis-12 conjugated linoleic acid (t10,c12-CLA) stimulated the growth of
      established ErbB2-overexpressing mammary tumors by 30% and increased the number
      of new tumors from 11% to 82%. Additionally, when t10,c12-CLA supplementation of
      ErbB2 transgenic mice was initiated at 21 weeks of age, a time just prior to
      tumor appearance, overall survival was decreased from 46.4 weeks in the control
      to 39.0 weeks in the CLA group, and survival after detection of a palpable tumor
      from 7.5 to 4.6 weeks. Short-term supplementation from 10 to 14 weeks or 21 to 25
      weeks of age temporarily accelerated tumor development, but over the long term,
      there was no significant effect on mammary tumorigenesis. Long term as well as a
      short 4-week supplementation increased mammary epithelial hyperplasia and lobular
      development, and altered the mammary stroma; this was reversible in mice returned
      to the control diet. t10,c12-CLA altered proliferation and apoptosis of the
      mammary epithelium, although this differed depending on the length of
      administration and/or the age of the mice. The increased tumor development with
      t10,c12-CLA was associated with increased phosphorylation of the IGF-I/insulin
      receptor, as well as increased signaling through the mitogen-activated protein
      kinase kinase (MEK)/extracellular signal-regulated kinase and
      phosphatidylinositol 3-kinase/Akt pathways; however, neither phospho-ErbB2 nor
      ErbB2 was altered.

PMID- 18339687
TI  - Central and peripheral administration of kisspeptin activates gonadotropin but
      not somatotropin secretion in prepubertal gilts.
AB  - It is well established that kisspeptin signaling is necessary for the onset of
      puberty in laboratory animals. However, the role that kisspeptin may have in
      regulating puberty in large domestic animals is unknown. We tested the hypothesis
      that either central or peripheral infusion of kisspeptin would stimulate
      gonadotropin and GH secretion in prepubertal gilts. In experiment 1, prepubertal
      gilts were fitted with i.c.v. cannula and indwelling jugular catheters. Animals
      were randomly assigned to receive 0, 10, or 100 microg kisspeptin in saline. In
      experiment 2, prepubertal gilts, fitted with indwelling jugular catheters,
      randomly received 0, 1, 2.5, or 5 mg kisspeptin in saline intravenously. Serial
      blood samples were collected every 15 min for 3 h before and 5 h after infusions,
      and serum concentrations of LH, FSH, and GH were determined. Mean concentrations
      of LH and FSH remained at basal levels for control animals but were increased
      (P<0.001) for animals receiving i.c.v. infusion of kisspeptin. Area under the LH
      and FSH curves following i.c.v. infusion of kisspeptin increased (P<0.001) in a
      dose-dependent manner. Concentrations of GH were unaffected by i.c.v. treatment.
      Peripheral administration of kisspeptin increased (P<0.05) serum concentrations
      of LH but not FSH or GH. Thus, kisspeptin can activate gonadotropic but not
      somatotropic hormone secretion in prepubertal gilts. The present data support the
      concept that kisspeptin plays a role in the mechanism involved in initiating
      puberty in swine.

PMID- 18339688
TI  - Is blood cardioplegia superior to crystalloid cardioplegia?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether blood cardioplegia is clinically
      superior to crystalloid cardioplegia for myocardial protection. Altogether 501
      papers were identified. We selected 22 papers that represented the best evidence
      to answer the question. The authors, journal, date and country of publication,
      patient group studied, study type, relevant outcomes and results of these papers
      are tabulated. This is a difficult topic to review, as the techniques studied in
      the many trials performed vary widely. Factors which may vary include warm or
      cold blood cardioplegia, antegrade and retrograde administration, systemic
      hypothermia or normothermia, topical heart cooling, high and low potassium
      solutions, 'hot shots', warm induction, volume of cardioplegia, patient factors
      and bypass times. However, three papers stand out. The meta-analysis of 34
      randomised trials by Prof Fremes (2006) found a significantly lower incidence of
      low output syndrome (LOS) and CK-MB release with blood cardioplegia. He found no
      differences in myocardial infarction or mortality. This meta-analysis was
      confounded, however, by the fact that he was unable to extract data on LOS and CK
      MB from the two largest trials which contributed over half the patients in his
      paper and are significantly larger than all other studies. The first paper by
      Ovrum (2006) randomised 1440 patients to antegrade cold blood or crystalloid and
      found no clinical differences, and the second paper by Martin (1994) of 1001
      patients compared warm blood to cold crystalloid but the study had to be stopped
      due to a high incidence of neurological events in the warm blood group. We
      reviewed a further 18 randomised trials reporting over 50 patients. Of these, 10
      reported some statistically significant clinical outcomes in favour of blood
      cardioplegia and five reported statistically significant differences in enzyme
      release in favour of blood cardioplegia. A recent survey of UK practice found
      that 56% of surgeons use cold blood cardioplegia, 14% use warm blood
      cardioplegia, 14% use crystalloid cardioplegia, 21% use retrograde infusion and
      16% do not use any cardioplegia. The papers presented in our review support most
      of these practices!

PMID- 18339689
TI  - Calmodulin binding to M-type K+ channels assayed by TIRF/FRET in living cells.
AB  - Calmodulin (CaM) binds to KCNQ2-4 channels within their carboxy termini, where it
      regulates channel function. The existing data have not resolved the Ca2+
      dependence of the interaction between the channels and CaM. We performed
      glutathione S-transferase (GST)-pull-down assays between purified KCNQ2-4 carboxy
      termini and CaM proteins to determine the Ca2+ dependence of the interaction in
      vitro. The assays showed substantial Ca2+ dependence of the interaction of the
      channels with wild-type (WT) CaM, but not with dominant-negative (DN) CaM. To
      demonstrate CaM-channel interactions in individual living cells, we performed
      fluorescence resonance energy transfer (FRET) between ECFP-tagged KCNQ2-4
      channels and EYFP-tagged CaM expressed in CHO cells, performed under total
      internal reflection fluorescence (TIRF) microscopy, in which excitation light
      only penetrates several hundred nanometres into the cell, thus isolating membrane
      events. FRET was assayed between the channels and either WT or DN CaM, performed
      under conditions of normal [Ca2+]i, low [Ca2+]i or high [Ca2+]i induced by
      empirically optimized bathing solutions. The FRET data suggest a strong Ca2+
      dependence for the interaction between WT CaM and KCNQ2, but less so for KCNQ3
      and KCNQ4. FRET between all KCNQ2-4 channels and DN CaM was robust, and not
      significantly Ca2+ dependent. These data show interactions between CaM and KCNQ
      channels in living cells, and suggest that the interactions between KCNQ2-4
      channels and CaM are likely to have Ca2+-dependent and Ca2+-independent
      components.

PMID- 18339690
TI  - Haemodynamic responses to exercise, ATP infusion and thigh compression in humans:
      insight into the role of muscle mechanisms on cardiovascular function.
AB  - The muscle pump and muscle vasodilatory mechanism are thought to play important
      roles in increasing and maintaining muscle perfusion and cardiac output ((.)Q)
      during exercise, but their actual contributions remain uncertain. To evaluate the
      role of the skeletal muscle pump and vasodilatation on cardiovascular function
      during exercise, we determined leg and systemic haemodynamic responses in healthy
      men during (1) incremental one-legged knee-extensor exercise, (2) step-wise
      femoral artery ATP infusion at rest, (3) passive exercise (n=10), (4)femoral vein
      or artery ATP infusion (n=6), and (5) cyclic thigh compressions at rest and
      during passive and voluntary exercise (n=7). Incremental exercise resulted in
      progressive increases in leg blood flow (DeltaLBF 7.4 +/- 0.7 l min(-1)), cardiac
      output (Delta (.)Q 8.7 +/- 0.7 l min(-1)), mean arterial pressure (DeltaMAP 51 +/
      5 mmHg), and leg and systemic oxygen delivery and (.)VO2 . Arterial ATP infusion
      resulted in similar increases in (.)Q , LBF, and systemic and leg oxygen
      delivery, but central venous pressure and muscle metabolism remained unchanged
      and MAP was reduced. In contrast,femoral vein ATP infusion did not alter LBF,
      (.)Q or MAP. Passive exercise also increased blood flow (DeltaLBF 0.7 +/- 0.1 l
      min(-1)), yet the increase in muscle and systemic perfusion, unrelated to
      elevations in aerobic metabolism, accounted only for approximately 5% of peak
      exercise hyperaemia.Likewise, thigh compressions alone or in combination with
      passive exercise increased blood flow (DeltaLBF 0.5-0.7 l min(-1)) without
      altering (.)Q, MAP or (.)VO2. These findings suggest that the skeletal muscle
      pump is not obligatory for sustaining venous return, central venous
      pressure,stroke volume and (.)Q or maintaining muscle blood flow during one
      legged exercise in humans.Further, its contribution to muscle and systemic peak
      exercise hyperaemia appears to be minimal in comparison to the effects of muscle
      vasodilatation.

PMID- 18339691
TI  - Peri-implantation and late gestation maternal undernutrition differentially
      affect fetal sheep skeletal muscle development.
AB  - Poor prenatal nutrition is associated with a greater risk of adult glucose
      intolerance and insulin insensitivity in the offspring. Skeletal muscle is the
      primary tissue for glucose utilization, and insulin resistance in muscle is the
      earliest identifiable abnormality in the pre-diabetic patient. We investigated
      the effect of early and late gestation undernutrition on structure and markers of
      growth and glucose metabolism regulation in the fetal triceps brachii (TB, slow-
      and fast-twitch myofibres) and soleus (slow-twitch myofibres) muscles. Pregnant
      sheep were fed 100% nutrient requirements (C, n = 8) or a restricted diet peri
      implantation (PI, n = 9; 40%, 1-31 days gestation (dGA) (term approximately 147))
      or in late gestation (L, n = 6; 50%, 104-127 dGA). At 127 +/- 1 dGA we measured
      myofibre and capillary density in the fetal TB and soleus muscles, and mRNA
      levels in the TB of insulin receptor (InsR), glucose transporter-4 (GLUT-4) and
      type 1 insulin-like growth factor receptor (IGF-1R). Total myofibre and capillary
      densities were lower in the TB, but not the soleus, of PI and L fetuses. The
      predominant effect in the L group was on slow-twitch myofibres. In TB, InsR, GLUT
      4 and IGF-1R mRNA levels were greater in L group fetuses. Our finding of reduced
      myofibre density is consistent with a redistribution of resources at the expense
      of specific peripheral tissues by early and late gestation undernutrition which
      may be mediated by a decrease in capillary density. The increase in key
      regulatory components of glucose uptake following late gestation undernutrition
      may constitute a short-term compensation to maintain glucose homeostasis in the
      face of fewer type I (insulin-sensitive) myofibres. However, together these
      adaptations may influence the risk of later metabolic disease and thus our
      findings have implications for future strategies aimed at improving maternal
      diet.

PMID- 18339692
TI  - The contribution of intrapulmonary shunts to the alveolar-to-arterial oxygen
      difference during exercise is very small.
AB  - Exercise is well known to cause arterial PO2 to fall and the alveolar-arterial
      PO2 difference(Aa PO2 ) to increase. Until recently, the physiological basis for
      this was considered to be mostly ventilation/perfusion ((.)VA/(.)Q) inequality
      and alveolar-capillary diffusion limitation. Recently, arterio-venous shunting
      through dilated pulmonary blood vessels has been proposed to explain a
      significant part of the Aa PO2 during exercise. To test this hypothesis we
      determined venous admixture during 5 min of near-maximal, constant-load, exercise
      in hypoxia (in inspired O2 fraction, FIO2 , 0.13), normoxia (FIO2 , 0.21) and
      hyperoxia (FIO2 , 1.0) undertaken in balanced order on the same day in seven fit
      cyclists ((.)VO2max, 61.3 +/- 2.4 ml kg(-1) min(-1); mean +/- S.E.M.). Venous
      admixture reflects three causes of hypoxaemia combined: true shunt, diffusion
      limitation and ((.)VA/(.)Q) inequality. In hypoxia, venous admixture was 22.8 +/-
      2.5% of the cardiac output; in normoxia it was 3.5 +/- 0.5%; in hyperoxia it was
      0.5 +/- 0.2%. Since only true shunt accounts for venous admixture while breathing
      100% O2, the present study suggests that shunt accounts for only a very small
      portion of the observed venous admixture, Aa PO2 and hypoxaemia during heavy
      exercise.

PMID- 18339693
TI  - Distinct receptors underlie glutamatergic signalling in inspiratory rhythm
      generating networks and motor output pathways in neonatal rat.
AB  - Despite the enormous diversity of glutamate (Glu) receptors and advances in
      understanding recombinant receptors, native Glu receptors underlying functionally
      identified inputs in active systems are poorly defined in comparison. In the
      present study we use UBP-302, which antagonizes GluR5 subunit-containing kainate
      (KA) receptors at < or = 10 microm, but other KA and AMPA receptors at > or = 100
      microm, and rhythmically active in vitro preparations of neonatal rat to explore
      the contribution of non-NMDA receptor signalling in rhythm-generating and motor
      output compartments of the inspiratory network. At 10 microm, UBP-302 had no
      effect on inspiratory burst frequency or amplitude. At 100 microm, burst
      amplitude recorded from XII, C1 and C4 nerve roots was significantly reduced, but
      frequency was unaffected. The lack of a frequency effect was confirmed when local
      application of UBP-302 (100 microm) into the pre-Botzinger complex (preBotC) did
      not affect frequency but substance P evoked a 2-fold increase. A UBP-302
      sensitive (10 microm), ATPA-evoked frequency increase, however, established that
      preBotC networks are sensitive to GluR5 activation. Whole-cell recordings
      demonstrated that XII motoneurons also express functional GluR5-containing KA
      receptors that do not contribute to inspiratory drive, and confirmed the dose
      dependence of UBP-302 actions on KA and AMPA receptors. Our data provide the
      first evidence that the non-NMDA (most probably AMPA) receptors mediating
      glutamatergic transmission within preBotC inspiratory rhythm-generating networks
      are pharmacologically distinct from those transmitting drive to inspiratory
      motoneurons. This differential expression may ultimately be exploited
      pharmacologically to separately counteract depression of central respiratory
      rhythmogenesis or manipulate the drive to motoneurons controlling airway and pump
      musculature.

PMID- 18339694
TI  - Emergence of brain-derived neurotrophic factor-induced postsynaptic potentiation
      of NMDA currents during the postnatal maturation of the Kolliker-Fuse nucleus of
      rat.
AB  - The Kolliker-Fuse nucleus (KF) contributes essentially to respiratory pattern
      formation and adaptation of breathing to afferent information. Systems physiology
      suggests that these KF functions depend on NMDA receptors (NMDA-R). Recent
      investigations revealed postnatal changes in the modulation of glutamatergic
      neurotransmission by brain-derived neurotrophic factor (BDNF) in the KF.
      Therefore, we investigated postnatal changes in NMDA-R subunit composition and
      postsynaptic modulation of NMDA-R-mediated currents by BDNF in KF slice
      preparations derived from three age groups (neonatal: postnatal day (P) 1-5;
      intermediate: P6-13; juvenile: P14-21). Immunohistochemistry showed a
      developmental up-regulation of the NR2D subunit. This correlated with a
      developmental increase in decay time of NMDA currents and a decline of
      desensitization in response to repetitive exogenous NMDA applications. Thus,
      developmental up-regulation of the NR2D subunit, which reduces the Mg(2+) block
      of NMDA-R, causes these specific changes in NMDA current characteristics. This
      may determine the NMDA-R-dependent function of the mature KF in the control of
      respiratory phase transition. Subsequent experiments revealed that bath
      application of BDNF progressively potentiated these repetitively evoked NMDA
      currents only in intermediate and juvenile age groups. Pharmacological inhibition
      of protein kinase C (PKC), as a downstream component of the BDNF-tyrosine kinase
      B receptor (trkB) signalling, prevented BDNF-induced potentiation of NMDA
      currents. BDNF-induced potentiation of NMDA currents in later developmental
      stages might be essential for synaptic plasticity during the adaptation of the
      breathing pattern in response to peripheral/central commands. The lack of
      plasticity in neonatal neurones strengthens the hypothesis that the respiratory
      network becomes permissive for activity-dependent plasticity with ongoing
      postnatal development.

PMID- 18339695
TI  - Involvement of AMPA receptor desensitization in short-term synaptic depression at
      the calyx of Held in developing rats.
AB  - Paired-pulse facilitation (PPF) and depression (PPD) are forms of short-term
      plasticity that are generally thought to reflect changes in transmitter release
      probability. However, desensitization of postsynaptic AMPA receptors (AMPARs)
      significantly contributes to PPD at many glutamatergic synapses. To clarify the
      involvement of AMPAR desensitization in synaptic PPD, we compared PPD with AMPAR
      desensitization, induced by paired-pulse glutamate application in patches excised
      from postsynaptic cells at the calyx of Held synapse of developing rats. We found
      that AMPAR desensitization contributed significantly to PPD before the onset of
      hearing (P10-12), but that its contribution became negligible after hearing
      onset. During postnatal development (P7-21) the recovery of AMPARs from
      desensitization became faster. Concomitantly, glutamate sensitivity of AMPAR
      desensitization declined. Single-cell reverse transcription-polymerase chain
      reaction (RT-PCR) analysis indicated a developmental decline of GluR1 expression
      that correlated with speeding of the recovery of AMPARs from desensitization.
      Transmitter release probability declined during the second postnatal week (P7
      14). Manipulation of the extracellular Ca2+/Mg2+ ratio, to match release
      probability at P7-8 and P13-15 synapses, revealed that the release probability is
      also an important factor determining the involvement of AMPAR desensitization in
      PPD. We conclude that the extent of involvement of AMPAR desensitization in short
      term synaptic depression is determined by both pre- and postsynaptic mechanisms.

PMID- 18339696
TI  - Analysis of circulating forms of proBNP and NT-proBNP in patients with severe
      heart failure.
AB  - BACKGROUND: The specific forms of pro-B-type natriuretic peptide (proBNP) that
      occur in human blood are not yet clear. We demonstrated the presence of several
      proBNP forms in human plasma with a new affinity chromatography method that can
      be used in combination with nano-liquid chromatography electrospray ionization
      tandem mass spectrometry (nano-LC-ESI-MS/MS). METHODS: For affinity
      chromatography, we coupled Fab' fragments of polyclonal sheep antibodies specific
      for N-terminal proBNP (NT-proBNP) epitope 1-21 to silica beads. We connected a
      column (10 mm x 0.8 mm inner diameter) packed with these beads to a trypsin
      reactor and used a preconcentrator in combination with a fritless nanospray
      column to perform MS analyses of proBNP forms in preextracted and non
      preextracted samples of plasma from patients with severe heart failure (HF). We
      used Western blotting in deglycosylation experiments to confirm the shifts in
      proBNP and NT-proBNP masses. RESULTS: Tandem MS experiments demonstrated the
      presence of both NT-proBNP and circulating proBNP in preextracted samples of
      plasma from patients with severe HF, and Western blotting analyses revealed 2
      bands of approximately 23 kDa and 13 kDa that shifted after deglycosylation to
      positions that corresponded to the locations of recombinant proBNP and synthetic
      NT-proBNP. CONCLUSIONS: We obtained clear evidence for circulating proBNP in
      patients with severe HF and provided the first demonstration of O-glycosylation
      of NT-proBNP. The higher molecular masses for NT-proBNP and proBNP observed in
      the Western blotting analyses than those expected from calculations can be
      explained by O-glycosylation of these peptides in vivo.

PMID- 18339697
TI  - Immunodetection of glycosylated NT-proBNP circulating in human blood.
AB  - BACKGROUND: Brain natriuretic peptide (BNP) or NT-proBNP (N-terminal fragment of
      BNP precursor) measurements are recommended as aids in diagnosis and prognosis of
      patients with heart failure. Recently it has been shown that proBNP is O
      glycosylated in human blood. The goal of this study was to map sites on the NT
      proBNP molecule that should be recognized by antibodies used in optimal NT-proBNP
      assays. METHODS: We analyzed endogenous NT-proBNP by several immunochemical
      methods using a broad panel of monoclonal antibodies specific to different
      epitopes of the NT-proBNP molecule. RESULTS: Treatment of endogenous NT-proBNP by
      a mixture of glycosidases resulted in significant improvement of the interaction
      between deglycosylated NT-proBNP and monoclonal antibodies (MAbs) specific to the
      mid-fragment of the molecule. MAbs specific to the N- and C-terminal parts of NT
      proBNP (epitopes 13-24 and 63-76) were able to recognize glycosylated and
      deglycosylated protein with similar efficiency. CONCLUSIONS: The central part of
      endogenous NT-proBNP is glycosylated, making it almost "invisible" for the
      antibodies specific to the mid-fragment of the molecule. Thus sandwich assays
      using even one antibody (poly- or monoclonal) specific to the central part of the
      molecule could underestimate the real concentration of endogenous NT-proBNP. MAbs
      specific to the N- and C-terminal parts of NT-proBNP (epitopes 13-24 and 63-76)
      are the best candidates to be used in an assay for optimal NT-proBNP
      immunodetection.

PMID- 18339698
TI  - Tissue factor and monocyte chemoattractant protein-1 expression in hypertensive
      individuals with normal or increased carotid intima-media wall thickness.
AB  - BACKGROUND: People with hypertension display an inflammatory pattern that
      includes increased plasma concentrations of monocyte chemoattractant protein 1
      (MCP-1) and C-reactive protein (CRP) and enhanced expression of tissue factor
      (TF) mRNA in blood monocytes. METHODS: In this study, we investigated the
      relationship between CRP concentrations and TF and MCP-1 mRNA expression in
      unstimulated and lipopolysaccharide (LPS)-stimulated monocytes isolated from
      hypertensives with or without an increase in carotid intima-media thickness
      (IMT). We also investigated the expression of TF and MCP-1 mRNA and MCP-1 protein
      after in vitro addition of CRP to monocytes. We measured CRP (by
      immunonephelometry) and monocyte expression of TF and MCP-1 (by real-time PCR) in
      80 untreated hypertensive patients without clinical cardiovascular disease (CVD)
      or additional risk factors for CVD compared with 41 controls. Based on IMT
      measured by carotid Doppler ultrasonography, patients were classified into the
      categories of normal (< or =1 mm) or abnormal (>1 mm). TF and MCP-1 mRNA and MCP
      1 protein (by Western blotting) were measured after in vitro addition of CRP to
      monocytes from 10 randomized controls as well as 10 hypertensives with IMT < or
      =1 mm and 10 with IMT >1 mm. RESULTS: CRP and TF and MCP-1 mRNA concentrations
      were significantly higher in IMT >1 mm hypertensives vs those with IMT < or =1 mm
      and controls. CRP had no effect on monocyte TF mRNA from either hypertensives or
      controls. CRP-stimulated monocytes from hypertensives, however, showed increased
      MCP-1 mRNA and protein expression compared with controls and LPS-stimulated
      cells. CONCLUSIONS: Our findings suggest that the inflammatory response of blood
      monocytes plays an important role in the development of atherosclerosis and
      hypertension.

PMID- 18339699
TI  - Development of a multiplexed urine assay for prostate cancer diagnosis.
AB  - BACKGROUND: Several studies have demonstrated the value of DNA methylation in
      urine-based assays for prostate cancer diagnosis. However, a multicenter
      validation with a clinical prototype has not been published. METHODS: We
      developed a multiplexed, quantitative methylation-specific polymerase chain
      reaction (MSP) assay consisting of 3 methylation markers, GSTP1, RARB, and APC,
      and an endogenous control, ACTB, in a closed-tube, homogeneous assay format. We
      tested this format with urine samples collected after digital rectal examination
      from 234 patients with prostate-specific antigen (PSA) concentrations > or =2.5
      microg/L in 2 independent patient cohorts from 9 clinical sites. RESULTS: In the
      first cohort of 121 patients, we demonstrated 55% sensitivity and 80%
      specificity, with area under the curve (AUC) 0.69. In the second independent
      cohort of 113 patients, we found a comparable sensitivity of 53% and specificity
      of 76% (AUC 0.65). In the first cohort, as well as in a combined cohort, the MSP
      assay in conjunction with total PSA, digital rectal examination status, and age
      improved the AUC without MSP, although the difference was not statistically
      significant. Importantly, the GSTP1 cycle threshold value demonstrated a good
      correlation (R = 0.84) with the number of cores found to contain prostate cancer
      or premalignant lesions on biopsy. Moreover, samples that exhibited methylation
      for either GSTP1 or RARB typically contained higher tumor volumes at
      prostatectomy than those samples that did not exhibit methylation. CONCLUSIONS:
      These data confirm and extend previously reported studies and demonstrate the
      performance of a clinical prototype assay that should aid urologists in
      identifying men who should undergo biopsy.

PMID- 18339700
TI  - A Lisbon agenda on health innovation.

PMID- 18339701
TI  - Decentralization, re-centralization and future European health policy.

PMID- 18339702
TI  - Towards Bamako: a European perspective on the global health research agenda.

PMID- 18339703
TI  - Response to Hayden: Comment on 'ethnic cleansing' and 'genocide'.

PMID- 18339704
TI  - Role of Sp1 and HNF1 transcription factors in SGLT1 regulation during chronic
      intestinal inflammation.
AB  - In a rabbit model of chronic intestinal inflammation, we previously demonstrated
      that the activity of Na-glucose cotransporter (SGLT1), SLC5A1, is inhibited. This
      inhibition is secondary to a decrease in the number of cotransporters, indicating
      that the regulation of SGLT1 during chronic inflammation is at the level of
      transcription. However, the regulation of SGLT1 expression and the transcription
      factors involved in the regulation are not yet known. In this report, we describe
      the cloning and characterization of rabbit SGLT1 promoter and the identification
      of transcription factors affected in villus cells during chronic intestinal
      inflammation. The promoter sequence for SGLT1 gene was identified by using the
      publicly available rabbit genomic sequence. Even though rabbit SGLT1 promoter did
      not have considerable overall homology with other mammalian SGLT1 promoters, two
      specificity protein 1 (Sp1) and a hepatocyte nuclear factor 1 (HNF1) binding
      sites were highly conserved among the species. Rabbit SGLT1 cDNA was encoded by
      15 exons. Minimal promoter region determination showed that 196 nucleotides
      upstream of the transcription start site were sufficient for optimal promoter
      activity. This region encompassed two transcription factor binding sites, Sp1 and
      HNF1. For maximal SGLT1 promoter activity, these two transcription factor binding
      sites were essential, and their effect was synergistic, indicating that two
      separate regulatory pathways might be involved in their regulation. Using
      mobility shift assays, we further demonstrated that the binding of both Sp1 and
      HNF1 transcription factors to SGLT1 promoter regions were affected during chronic
      intestinal inflammation. Thus this report demonstrates that Sp1 and HNF1
      transcription factors act in concert to regulate SGLT1 transcription in the
      chronically inflamed intestine.

PMID- 18339705
TI  - Platelet-activating factor-induced chloride channel activation is associated with
      intracellular acidosis and apoptosis of intestinal epithelial cells.
AB  - Platelet-activating factor (PAF) is a phospholipid inter- and intracellular
      mediator implicated in intestinal injury primarily via induction of an
      inflammatory cascade. We find that PAF also has direct pathological effects on
      intestinal epithelial cells (IEC). PAF induces Cl(-) channel activation, which is
      associated with intracellular acidosis and apoptosis. Using the rat small IEC
      line IEC-6, electrophysiological experiments demonstrated that PAF induces Cl(-)
      channel activation. This PAF-activated Cl(-) current was inhibited by Ca(2+)
      chelation and a calcium calmodulin kinase II inhibitor, suggesting PAF activation
      of a Ca(2+)-activated Cl(-) channel. To determine the pathological consequences
      of Cl(-) channel activation, microfluorimetry experiments were performed, which
      revealed PAF-induced intracellular acidosis, which is also inhibited by the Cl(-)
      channel inhibitor 4,4'diisothiocyanostilbene-2,2'disulfonic acid and Ca(2+)
      chelation. PAF-induced intracellular acidosis is associated with caspase 3
      activation and DNA fragmentation. PAF-induced caspase activation was abolished in
      cells transfected with a pH compensatory Na/H exchanger construct to enhance H(+)
      extruding ability and prevent intracellular acidosis. As ClC-3 is a known
      intestinal Cl(-) channel dependent on both Ca(2+) and calcium calmodulin kinase
      II phosphorylation, we generated ClC-3 knockdown cells using short hairpin RNA.
      PAF induced Cl(-) current; acidosis and apoptosis were all significantly
      decreased in ClC-3 knockdown cells. Our data suggest a novel mechanism of PAF
      induced injury by which PAF induces intracellular acidosis via activation of the
      Ca(2+)-dependent Cl(-) channel ClC-3, resulting in apoptosis of IEC.

PMID- 18339706
TI  - Improved lactational nutrition and postnatal growth ameliorates impairment of
      glucose tolerance by uteroplacental insufficiency in male rat offspring.
AB  - Intrauterine growth restriction and accelerated postnatal growth predict
      increased risk of diabetes. Uteroplacental insufficiency in the rat restricts
      fetal growth but also impairs mammary development and postnatal growth. We used
      cross fostering to compare the influence of prenatal and postnatal nutritional
      restraint on adult glucose tolerance, insulin secretion, insulin sensitivity, and
      hypothalamic neuropeptide Y content in Wistar Kyoto rats at 6 months of age.
      Bilateral uterine vessel ligation (restricted) to induce uteroplacental
      insufficiency or sham surgery (control) was performed on d-18 gestation. Control,
      restricted, and reduced (reducing litter size of controls to match restricted)
      pups were cross fostered onto a control or restricted mother 1 d after birth.
      Restricted pups were born small compared with controls. Restricted males, but not
      females, remained lighter up to 6 months, regardless of postnatal environment. By
      10 wk, restricted-on-restricted males ate more than controls. At 6 months
      restricted-on-restricted males had increased hypothalamic neuropeptide Y content
      compared with other groups, and together with reduced-on-restricted males had
      increased retroperitoneal fat weight (percent body weight) compared with control
      on-controls. Restricted-on-restricted males had impaired glucose tolerance,
      reduced first-phase insulin secretion, but unaltered insulin sensitivity,
      compared with control-on-controls. In males, being born small and exposed to an
      impaired lactational environment adversely affects adult glucose tolerance and
      first-phase insulin secretion, but improving lactation partially ameliorates this
      condition. This study identifies early life as a target for intervention to
      prevent later diabetes after prenatal restraint.

PMID- 18339707
TI  - 3beta-Hydroxysteroid-delta24 reductase is a hydrogen peroxide scavenger,
      protecting cells from oxidative stress-induced apoptosis.
AB  - 3beta-Hydroxysteroid-Delta24 reductase (DHCR24) is an endoplasmic reticulum
      resident, multifunctional enzyme that possesses antiapoptotic and cholesterol
      synthesizing activities. To clarify the molecular basis of the former activity,
      we investigated the effects of hydrogen peroxide (H(2)O(2)) on embryonic
      fibroblasts prepared from DHCR24-knockout mice (DHCR24(-/-) mouse embryonic
      fibroblasts). H(2)O(2) exposure rapidly induced apoptosis, which was associated
      with sustained activation of apoptosis signal-regulating kinase-1 and stress
      activated protein kinases, such as p38 MAPK and c-Jun N-terminal kinase.
      Complementation of the mouse embryonic fibroblasts by adenovirus expressing
      DHCR24 attenuated the H(2)O(2)-induced kinase activation and apoptosis.
      Concomitantly, intracellular generation of reactive oxygen species (ROS) in
      response to H(2)O(2) was also diminished by the adenovirus, suggesting a ROS
      scavenging activity of DHCR24. Such antiapoptotic effects of DHCR24 were
      duplicated in pheochromocytoma PC12 cells infected with adenovirus. In addition,
      it was found that DHCR24 exerted cytoprotective effects in the tunicamycin
      induced endoplasmic reticulum stress by eliminating ROS. Finally, using in vitro
      synthesized and purified proteins, DHCR24 and its C-terminal deletion mutant were
      found to exhibit high H(2)O(2)-scavenging activity, whereas the N-terminal
      deletion mutant lost such activity. These results demonstrate that DHCR24 can
      directly scavenge H(2)O(2), thereby protecting cells from oxidative stress
      induced apoptosis.

PMID- 18339708
TI  - Molecular characterization of V59E NIS, a Na+/I- symporter mutant that causes
      congenital I- transport defect.
AB  - I(-) is actively transported into thyrocytes via the Na+/I(-) symporter (NIS), a
      key glycoprotein located on the basolateral plasma membrane. The cDNA encoding
      rat NIS was identified in our laboratory, where an extensive structure/function
      characterization of NIS is being conducted. Several NIS mutants have been
      identified as causes of congenital I(-) transport defect (ITD), including V59E
      NIS. ITD is characterized by low thyroid I(-) uptake, low saliva/plasma I(-)
      ratio, hypothyroidism, and goiter and may cause mental retardation if untreated.
      Studies of other ITD-causing NIS mutants have revealed valuable information
      regarding NIS structure/function. V59E NIS was reported to exhibit as much as 30%
      of the activity of wild-type NIS. However, this observation was at variance with
      the patients' phenotype of total lack of activity. We have thoroughly
      characterized V59E NIS and studied several amino acid substitutions at position
      59. We demonstrated that, in contrast to the previous report, V59E NIS is
      inactive, although it is properly targeted to the plasma membrane. Glu and all
      other charged amino acids or Pro at position 59 also yielded nonfunctional NIS
      proteins. However, I(-) uptake was rescued to different degrees by the other
      substitutions. Although the Km values for Na+ and I(-) were not altered in these
      active mutants, we found that the structural requirement for NIS function at
      position 59 is a neutral, helix-promoting amino acid. This result suggests that
      the region that contains V59 may be involved in intramembrane helix-helix
      interactions during the transport cycle without being in direct contact with the
      substrates.

PMID- 18339709
TI  - Discovery of a cholecystokinin-gastrin-like signaling system in nematodes.
AB  - Members of the cholecystokinin (CCK)/gastrin family of peptides, including the
      arthropod sulfakinins, and their cognate receptors, play an important role in the
      regulation of feeding behavior and energy homeostasis. Despite many efforts after
      the discovery of CCK/gastrin immunoreactivity in nematodes 23 yr ago, the
      identity of these nematode CCK/gastrin-related peptides has remained a mystery
      ever since. The Caenorhabditis elegans genome contains two genes with high
      identity to the mammalian CCK receptors and their invertebrate counterparts, the
      sulfakinin receptors. By using the potential C. elegans CCK receptors as a
      fishing hook, we have isolated and identified two CCK-like neuropeptides encoded
      by neuropeptide-like protein-12 (nlp-12) as the endogenous ligands of these
      receptors. The neuropeptide-like protein-12 peptides have a very limited neuronal
      expression pattern, seem to occur in vivo in the unsulfated form, and react
      specifically with a human CCK-8 antibody. Both receptors and ligands share a high
      degree of structural similarity with their vertebrate and arthropod counterparts,
      and also display similar biological activities with respect to digestive enzyme
      secretion and fat storage. Our data indicate that the gastrin-CCK signaling
      system was already well established before the divergence of protostomes and
      deuterostomes.

PMID- 18339710
TI  - Thyronamines are isozyme-specific substrates of deiodinases.
AB  - 3-Iodothyronamine (3-T 1 AM) and thyronamine (T AM) are novel endogenous
      signaling molecules that exhibit great structural similarity to thyroid hormones
      but apparently antagonize classical thyroid hormone (T(3)) actions. Their
      proposed biosynthesis from thyroid hormones would require decarboxylation and
      more or less extensive deiodination. Deiodinases (Dio1, Dio2, and Dio3) catalyze
      the removal of iodine from their substrates. Because a role of deiodinases in
      thyronamine biosynthesis requires their ability to accept thyronamines as
      substrates, we investigated whether thyronamines are converted by deiodinases.
      Thyronamines were incubated with isozyme-specific deiodinase preparations.
      Deiodination products were analyzed using a newly established method applying
      liquid chromatography and tandem mass spectrometry (LC-MS/MS). Phenolic ring
      deiodinations of 3,3',5'-triiodothyronamine (rT3AM), 3',5'-diiodothyronamine
      (3',5'-T2AM), and 3,3'-diiodothyronamine (3,3'-T2AM) as well as tyrosyl ring
      deiodinations of 3,5,3'-triiodothyronamine (T3AM) and 3,5-diiodothyronamine (3,5
      T2AM) were observed with Dio1. These reactions were completely inhibited by the
      Dio1-specific inhibitor 6n-propyl-2-thiouracil (PTU). Dio2 containing
      preparations also deiodinated rT(3)AM and 3',5'-T2AM at the phenolic rings but in
      a PTU-insensitive fashion. All thyronamines with tyrosyl ring iodine atoms were
      5(3)-deiodinated by Dio3-containing preparations. In functional competition
      assays, the newly identified thyronamine substrates inhibited an established
      iodothyronine deiodination reaction. By contrast, thyronamines that had been
      excluded as deiodinase substrates in LC-MS/MS experiments failed to show any
      effect in the competition assays, thus verifying the former results. These data
      support a role for deiodinases in thyronamine biosynthesis and contribute to
      confining the biosynthetic pathways for 3-T 1 AM and T 0 AM.

PMID- 18339711
TI  - A novel, functional, and highly divergent sex hormone-binding globulin that may
      participate in the local control of ovarian functions in salmonids.
AB  - A cDNA encoding for a novel rainbow trout SHBG was identified and characterized.
      Phylogenetic analysis showed that this novel SHBG, named SHBGb, was a highly
      divergent paralog of the classical SHBG (SHBGa) form previously known in
      vertebrates including zebrafish, seabass, and rainbow trout. Using all available
      sequences, no SHBGb-like sequence could be identified in any fish species besides
      Atlantic salmon. Rainbow trout SHBGa and SHBGb share only 26% sequence identity
      at the amino acid level and exhibit totally distinct tissue distribution, thus
      demonstrating a functional shift of SHBGb. Indeed, shbga mRNA was predominantly
      expressed in liver and spleen but could not be detected in the ovary, whereas
      shbgb had a predominant ovarian expression but could not be detected in liver.
      Despite its high divergence, rainbow trout SHBGb expressed in COS-7 cells could
      bind estradiol and testosterone with high affinity and specificity. Both rainbow
      trout shbgb mRNA and proteins were localized to the granulosa cells of
      vitellogenic ovarian follicles, whereas SHBGb immunoreactivity was also found in
      theca cells. Finally, shbgb ovarian mRNA expression exhibited a significant drop
      between late vitellogenesis and oocyte maturation at a time when ovarian
      aromatase (cyp19a) gene expression and estradiol circulating levels exhibited a
      dramatic decrease. Together, these observations show that SHBGb is a functional
      and highly divergent SHBG paralog probably arising from a salmonid-specific
      duplication of the shbg gene.

PMID- 18339712
TI  - Prokineticin 1 signaling and gene regulation in early human pregnancy.
AB  - Prokineticin 1 (PROK1) is a recently described protein with a wide range of
      functions including tissue-specific angiogenesis, modulation of inflammatory
      responses, and regulation of hematopoiesis. The objective of this study was to
      investigate the role of PROK1 and prokineticin receptor 1 (PROKR1) in human
      endometrium during early pregnancy. PROK1 and PROKR1 expression is significantly
      elevated in first-trimester decidua, compared with nonpregnant endometrium.
      Expression of PROK1 and PROKR1 was localized in glandular epithelial and various
      cellular compartments within the stroma. To investigate the signaling pathways
      and target genes activated by PROK1, we generated an endometrial epithelial cell
      line stably expressing PROKR1 (Ishikawa PROKR1 cells). PROK1-PROKR1 interaction
      induced inositol phosphate mobilization and sequential phosphorylation of c-Src,
      epidermal growth factor receptor, and ERK 1/2. Gene microarray analysis on RNA
      extracted from Ishikawa PROKR1 cells treated with 40 nm PROK1 for 8 h revealed 49
      genes to be differentially regulated. A number of these genes, including
      cyclooxygenase (COX)-2, leukemia inhibitory factor, IL-6, IL-8, and IL-11 are
      regulated in the endometrium during implantation and early pregnancy. We
      subsequently investigated the effect of PROK1 on expression of COX-2 in Ishikawa
      PROKR1 cells and first-trimester decidua. COX-2 mRNA and protein expression, and
      prostaglandin synthesis, were elevated in response to treatment with PROK1.
      Moreover, expression of COX-2 by PROK1 was dependent on activation of the Gq
      phospholipase C-beta-cSrc-epidermal growth factor receptor-MAPK/ERK kinase
      pathway. These data demonstrate that PROK1 and PROKR1 expression is elevated in
      human decidua during early pregnancy and that PROK1-PROKR1 interaction regulates
      expression of a host of implantation-related genes.

PMID- 18339713
TI  - An estrogen receptor-alpha knock-in mutation provides evidence of ligand
      independent signaling and allows modulation of ligand-induced pathways in vivo.
AB  - Estrogen-nonresponsive estrogen receptor-alpha (ERalpha) knock-in (ENERKI) mice
      were generated to distinguish between ligand-induced and ligand-independent ER
      alpha actions in vivo. These mice have a mutation [glycine 525 to leucine
      (G525L)] in the ligand-binding domain of ERalpha, which significantly reduces
      ERalpha interaction with and response to endogenous estrogens, whereas not
      affecting growth factor activation of ligand-independent pathways. ENERKI mice
      had hypoplastic uterine tissues and rudimentary mammary gland ductal trees.
      Females were infertile due to anovulation, and their ovaries contained
      hemorrhagic cystic follicles because of chronically elevated levels of LH. The
      ENERKI phenotype confirmed that ligand-induced activation of ERalpha is crucial
      in the female reproductive tract and mammary gland development. Growth factor
      treatments induced uterine epithelial proliferation in ovariectomized ENERKI
      females, directly demonstrating that ERalpha ligand-independent pathways were
      active. In addition, the synthetic ERalpha selective agonist propyl pyrazole
      triol (PPT) and ER agonist diethylstilbestrol (DES) were still able to activate
      ligand-induced G525L ERalpha pathways in vitro. PPT treatments initiated at
      puberty stimulated ENERKI uterine development, whereas neonatal treatments were
      needed to restore mammary gland ductal elongation, indicating that neonatal
      ligand-induced ERalpha activation may prime mammary ducts to become more
      responsive to estrogens in adult tissues. This is a useful model for in vivo
      evaluation of ligand-induced ERalpha pathways and temporal patterns of response.
      DES did not stimulate an ENERKI uterotrophic response. Because ERbeta may
      modulate ERalpha activation and have an antiproliferative function in the uterus,
      we hypothesize that ENERKI animals were particularly sensitive to DES-induced
      inhibition of ERalpha due to up-regulated uterine ERbeta levels.

PMID- 18339714
TI  - Superoxide destabilization of beta-catenin augments apoptosis of high-glucose
      stressed mesangial cells.
AB  - Intense mesangial cell apoptosis contributes to the pathogenesis of diabetic
      nephropathy. Although reactive oxygen radicals and Wnt signaling components are
      potent regulators that modulate renal tissue remodeling and morphogenesis, cross
      talk between oxidative stress and Wnt/beta-catenin signaling in controlling high
      glucose-impaired mesangial cell survival and renal function have not been tested.
      In this study, high glucose induced Ras and Rac1 activation, superoxide burst,
      and Wnt5a/beta-catenin destabilization and subsequently promoted caspase-3 and
      poly (ADP-ribose) polymerase cleavage and apoptosis in mesangial cell cultures.
      The pharmacological and genetic suppression of superoxide synthesis by superoxide
      dismutase and diphenyloniodium, dominant-negative Ras (S17N), and dominant
      negative Rac1 (T17N) abrogated high-glucose-induced glycogen synthase kinase (GSK
      3beta) activation and caspase-3 and poly (ADP-ribose) polymerase degradation.
      Inactivation of Ras and Racl also reversed Wnt/beta-catenin expression and
      survival of mesangial cells. Stabilization of beta-catenin by the transfection of
      stable beta-catenin (Delta45) and kinase-inactive GSK-3beta attenuated high
      glucose-mediated mesangial cell apoptosis. Exogenous superoxide dismutase
      administration attenuated urinary protein secretion in diabetic rats and
      abrogated diabetes-mediated reactive oxygen radical synthesis in renal glomeruli.
      Immunohistological observation revealed that superoxide dismutase treatment
      abrogated diabetes-induced caspase-3 cleavage and terminal deoxynucleotidyl
      transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL)
      and increased Wnt5a/beta-catenin expression in renal glomeruli. Taken together,
      high glucose induced oxidative stress and apoptosis in mesangial cells. The Ras
      and Rac1 regulation of superoxide appeared to raise apoptotic activity by
      activating GSK-3beta and inhibiting Wnt5a/beta-catenin signaling. Controlling
      oxidative stress and Wnt/beta-catenin signaling has potential for protecting
      renal tissue against the deleterious effect of high glucose.

PMID- 18339715
TI  - Insulin-like growth factor II activates phosphatidylinositol 3-kinase
      protooncogenic protein kinase 1 and mitogen-activated protein kinase cell
      Signaling pathways, and stimulates migration of ovine trophectoderm cells.
AB  - IGF-II, a potent stimulator of cellular proliferation, differentiation, and
      development, regulates uterine function and conceptus growth in several species.
      In situ hybridization analyses found that IGF-II mRNA was most abundant in the
      caruncular endometrial stroma of both cyclical and pregnant ewes. In the
      intercaruncular endometrium, IGF-II mRNA transitioned from stroma to luminal
      epithelium between d 14 and 20 of pregnancy. IGF-II mRNA was present in all cells
      of the conceptus but was particularly abundant in the yolk sac.
      Immunohistochemical analyses revealed that phosphorylated (p)-protooncogenic
      protein kinase 1, p-ribosomal protein S6 kinase, p-ERK1/2, and p-P38 MAPK
      proteins were present at low levels in a majority of endometrial cells but were
      most abundant in the nuclei of endometrial luminal epithelium and conceptus
      trophectoderm of pregnant ewes. In mononuclear trophectoderm cells isolated from
      d-15 conceptuses, IGF-II increased the abundance of p-pyruvate dehydrogenase
      kinase 1, p-protooncogenic protein kinase 1, p-glycogen synthase kinase 3B, p
      FK506 binding protein 12-rapamycin associated protein 1, and p-ribosomal protein
      S6 kinase protein within 15 min, and the increase was maintained for 90 min. IGF
      II also elicited a rapid increase in p-ERK1/2 and p-P38 MAPK proteins that was
      maximal at 15 or 30 min posttreatment. Moreover, IGF-II increased migration of
      trophectoderm cells. Collectively, these results support the hypothesis that IGF
      II coordinately activates multiple cell signaling pathways critical to survival,
      growth, and differentiation of the ovine conceptus during early pregnancy.

PMID- 18339716
TI  - Dual effect of the adapter growth factor receptor-bound protein 14 (grb14) on
      insulin action in primary hepatocytes.
AB  - Tight control of insulin action in liver is a crucial determinant for the
      regulation of energy homeostasis. Growth factor receptor-bound protein 14 (Grb14)
      is a molecular adapter, highly expressed in liver, which binds to the activated
      insulin receptor and inhibits its tyrosine kinase activity. The physiological
      role of Grb14 in liver metabolism was unexplored. In this study we used RNA
      interference to investigate the consequences of Grb14 decrease on insulin
      regulated intracellular signaling, and on glucose and lipid metabolism in mouse
      primary cultured hepatocytes. In Grb14-depleted hepatocytes, insulin-induced
      phosphorylation of Akt, and of its substrates glycogen synthase kinase 3 and fork
      head box protein 1, was increased. These effects on insulin signaling are in
      agreement with the selective inhibitory effect of Grb14 on the receptor kinase.
      However, the metabolic and genic effects of insulin were differentially regulated
      after Grb14 down-regulation. Indeed, the insulin-mediated inhibition of hepatic
      glucose production and gluconeogenic gene expression was slightly increased.
      Surprisingly, despite the improved Akt pathway, the induction by insulin of
      sterol regulatory element binding protein-1c maturation was totally blunted. As a
      result, in the absence of Grb14, glycogen synthesis as well as glycolytic and
      lipogenic gene expression were not responsive to the stimulatory effect of
      insulin. This study provides evidence that Grb14 exerts a dual role on the
      regulation by insulin of hepatic metabolism. It inhibits insulin receptor
      catalytic activity, and acts also at a more distal step, i.e. sterol regulatory
      element binding protein-1c maturation, which effect is predominant under short
      term inhibition of Grb14 expression.

PMID- 18339717
TI  - Blockade of tumor necrosis factor (TNF) receptor type 1-mediated TNF-alpha
      signaling protected Wistar rats from diet-induced obesity and insulin resistance.
AB  - TNF-alpha plays an important role in the pathogenesis of obesity and insulin
      resistance in which the effect of TNF-alpha signaling via TNF receptor type 1
      (TNFR1) largely remains controversial. To delineate the role of TNFR1-mediated
      TNF-alpha signaling in the pathogenesis of this disorder, a TNFR1 blocking
      peptide-Fc fusion protein (TNFR1BP-Fc) was used for the present study. Wistar
      rats were fed a high-fat/high-sucrose (HFS) diet for 16 wk until obesity and
      insulin resistance developed. In comparison with increased body weight and fat
      weight, enlarged adipocytes, and hypertriglyceridemia in the obese state, the
      subsequent 4-wk treatment with TNFR1BP-Fc resulted in significant weight loss
      characterized by decreased fat pad weight and adipocyte size and reduced plasma
      triglycerides. Furthermore, obesity-induced insulin resistance, including
      hyperinsulinemia, elevated C-peptide, higher degree of hyperglycemia after
      glucose challenge, and less hypoglycemic response to insulin, was markedly
      improved, and the compensatory hyperplasia and hypertrophy of pancreatic islets
      were reduced. Interestingly, treatment with TNFR1BP-Fc markedly suppressed
      systemic TNF-alpha release and its local expression in pancreatic islets and
      muscle and adipose tissues. In addition, blockage of TNFR1-mediated TNF-alpha
      signaling in obese rats significantly enhanced tyrosine phosphorylation of
      insulin receptor substrate 1 (IRS-1) in the muscle and fat tissues. Our results
      strongly suggest a pivotal role for TNFR1-mediated TNF-alpha signaling in the
      pathogenesis of obesity and insulin resistance. Thus, TNFR1BP-Fc may be a good
      candidate for the treatment of this disease.

PMID- 18339719
TI  - Diffusion tensor MR imaging and fiber tractography: technical considerations.
AB  - This second article of the 2-part review builds on the theoretic background
      provided by the first article to cover the major technical factors that affect
      image quality in diffusion imaging, including the acquisition sequence, magnet
      field strength, gradient amplitude, and slew rate as well as multichannel radio
      frequency coils and parallel imaging. The sources of many common diffusion image
      artifacts are also explored in detail. The emphasis is on optimizing these
      technical factors for state-of-the-art diffusion-weighted imaging and diffusion
      tensor imaging (DTI) based on the best available evidence in the literature. An
      overview of current methods for quantitative analysis of DTI data and fiber
      tractography in clinical research is also provided.

PMID- 18339718
TI  - Paired-like homeodomain transcription factors 1 and 2 regulate follicle
      stimulating hormone beta-subunit transcription through a conserved cis-element.
AB  - Paired-like homeodomain transcription factors (PITX) regulate the activity of
      pituitary hormone-encoding genes. Here, we examined mechanisms through which the
      family of PITX proteins control murine FSH beta-subunit (Fshb) transcription. We
      observed that endogenous PITX1 and PITX2 isoforms from murine LbetaT2 gonadotrope
      cells could bind a highly conserved proximal cis-element. Transfection of PITX1
      or PITX2C in heterologous cells stimulated both murine and human Fshb/FSHB
      promoter-reporter activities, and in both cases, mutation of the critical cis
      element abrogated these effects. In homologous LbetaT2 cells, the same mutation
      decreased basal reporter activity and greatly reduced activin A-stimulated
      transcription from murine and human promoter-reporters. Transfecting dominant
      negative forms of PITX1 or PITX2C or knocking down PITX1 or -2 expression by RNA
      interference in LbetaT2 cells inhibited murine Fshb transcription, confirming
      roles for endogenous PITX proteins. Both PITX1 and PITX2C interacted with Smad3
      (an effector of the activin signaling cascade in these cells) in coprecipitation
      experiments, and the PITX binding site mutation greatly inhibited Smad2/3/4
      stimulated Fshb transcription. In summary, both PITX1 and PITX2C regulate murine
      and human Fshb/FSHB transcription through a conserved cis-element in the proximal
      promoter. Furthermore, the data indicate both common and distinct mechanisms of
      PITX1 and PITX2C action.

PMID- 18339720
TI  - Diffusion tensor MR imaging and fiber tractography: theoretic underpinnings.
AB  - In this article, the underlying theory of clinical diffusion MR imaging,
      including diffusion tensor imaging (DTI) and fiber tractography, is reviewed.
      First, a brief explanation of the basic physics of diffusion-weighted imaging
      (DWI) and apparent diffusion coefficient (ADC) mapping is provided. This is
      followed by an overview of the additional information that can be derived from
      the diffusion tensor, including diffusion anisotropy, color-encoded fiber
      orientation maps, and 3D fiber tractography. This article provides the requisite
      background for the second article in this 2-part review to appear next month,
      which covers the major technical factors that affect image quality in diffusion
      MR imaging, including the acquisition sequence, magnet field strength, gradient
      amplitude and slew rate, and multichannel radio-frequency coils and parallel
      imaging. The emphasis is on optimizing these factors for state-of-the-art DWI and
      DTI based on the best available evidence in the literature.

PMID- 18339721
TI  - Eccentric stenosis of the carotid artery associated with ipsilateral
      cerebrovascular events.
AB  - BACKGROUND AND PURPOSE: Eccentric stenosis of the coronary artery is associated
      with plaque disruption and acute coronary syndrome. The purpose of the present
      study was to determine whether eccentric stenosis of the carotid artery
      contributes to cerebrovascular events. MATERIALS AND METHODS: Of 6859 patients
      with vascular diseases who underwent duplex carotid ultrasonography, we studied
      512 internal carotid arteries in 441 patients who had a maximum area stenosis at
      or more than 70%, which corresponds with approximately 50% or more by the NASCET
      method. The maximal (A) and minimal wall thicknesses (B) were measured on cross
      sectional sonography images, and an eccentricity index was calculated using the
      following formula: (A - B)/A. Arteries in the lowest quartile of the eccentricity
      index (<0.69) were defined as having a concentric stenosis, whereas the others
      were defined as having eccentric stenosis. The underlying clinical
      characteristics and plaque morphologies, as well as the occurrence of ipsilateral
      ischemic stroke or transient ischemic attack in the preceding year, were compared
      between patients with eccentric and concentric stenosis. RESULTS: Patient
      characteristics and plaque morphology were similar between the 2 groups.
      Cerebrovascular events occurred more frequently ipsilaterally to the artery with
      eccentric stenosis (13.5%) than to the artery with concentric stenosis (5.5%; P =
      .013); the difference was more evident when cerebrovascular events of presumed
      carotid arterial origin were assessed (P = .005). After adjusting for risk
      factors and plaque morphology, eccentric stenosis was independently related to
      the presence of recent cerebrovascular events (odds ratio = 2.76; 95% confidence
      interval = 1.19-6.40). CONCLUSIONS: In patients with an area carotid stenosis of
      70% or more, eccentric plaque was associated with a significantly increased
      incidence of ipsilateral cerebrovascular events compared with patients with
      concentric stenosis.

PMID- 18339722
TI  - High-resolution diffusion-weighted MR imaging of the human lumbosacral plexus and
      its branches based on a steady-state free precession imaging technique at 3T.
AB  - 3D diffusion-weighted steady-state free precession imaging (3D DW-SSFP) with
      isotropic resolution was performed to delineate structures of the human
      lumbosacral plexus (LSP). 3D DW-SSFP clearly revealed detailed anatomy of the LSP
      and its branches. Our data suggest that the sequence based on 3D DW-SSFP can be
      used for high-resolution MR imaging of the peripheral nervous system.

PMID- 18339723
TI  - Proton MR spectroscopy in the evaluation of cerebral metabolism in patients with
      fibromyalgia: comparison with healthy controls and correlation with symptom
      severity.
AB  - BACKGROUND AND PURPOSE: Widespread pain sensitivity in patients with fibromyalgia
      (FM) suggests a central nervous system (CNS)-processing problem. Therefore, it is
      conceivable that metabolic alterations exist in pain-processing brain regions of
      people with FM compared with healthy controls (HC) and that such metabolic data
      could correlate with clinical symptoms. The purpose of this study was to test
      these hypotheses using proton MR spectroscopy ((1)H-MR spectroscopy). MATERIALS
      AND METHODS: There were 21 patients with FM and 27 HC who underwent conventional
      structural MR imaging and additional 2D-chemical shift imaging (CSI) MR
      spectroscopy sequences. For the 2D-CSI spectroscopy, larger volumes of interest
      (VOIs) were centered at the level of the basal ganglia and the supraventricular
      white matter. Within these larger areas, 16 smaller voxels were placed in a
      number of regions previously implicated in pain processing. N-acetylaspartate
      (NAA)/creatine(Cr), choline (Cho)/Cr and NAA/Cho ratios were calculated for each
      voxel. Subjects underwent clinical and experimental pain assessment. RESULTS:
      Mean metabolite ratios and ratio variability for each region were analyzed by
      using repeated-measures analysis of variance (ANOVA). Correlations between
      clinical symptoms and metabolite ratios were assessed. Cho/Cr variability in the
      right dorsolateral prefrontal cortex (DLPFC) was significantly different in the 2
      groups; a significant correlation between Cho/Cr in this location and clinical
      pain was present in the FM group. Evoked pain threshold correlated significantly
      with NAA/Cho ratios in the left insula and left basal ganglia. CONCLUSION: Our
      data suggest that there are baseline differences in the variability of brain
      metabolite relative concentrations between patients with FM and HC, especially in
      the right DLPFC. Furthermore, there are significant correlations between
      metabolite ratios and clinical and experimental pain parameters in patients with
      FM.

PMID- 18339724
TI  - Head and neck paragangliomas: value of contrast-enhanced 3D MR angiography.
AB  - BACKGROUND AND PURPOSE: A rapid and accurate MR imaging technique would be
      beneficial to assess paragangliomas in the head and neck and to distinguish them
      from other lesions. The purpose of this study was to determine whether the
      combination of elliptic centric contrast-enhanced MR angiography (CE-MRA) and
      unenhanced and enhanced spin-echo imaging (conventional MR imaging) is more
      accurate than conventional MR imaging alone to assess paragangliomas in the head
      and neck. MATERIALS AND METHODS: Three radiologists retrospectively and
      independently reviewed CE-MRA and conventional MR imaging in 27 patients with
      suspected paragangliomas. The overall image quality and the probability of
      paraganglioma were recorded. The results of each technique and their combination
      were analyzed for sensitivity and specificity. Receiver operating characteristic
      (ROC) analyses were performed by using histologic analysis, imaging, and/or
      clinical findings as the reference standard. RESULTS: Forty-six lesions were
      found in 27 patients. In the assessment of paragangliomas, the combination of
      conventional MR imaging and CE-MRA was significantly superior to conventional MR
      imaging alone. Sensitivity and specificity respectively were the following: for
      CE-MRA, 100% and 94%; and for conventional MR imaging, 94% and 41%. The
      specificity of CE-MRA was significantly higher than that of conventional MR
      imaging (P = .004). There was good-to-excellent interobserver agreement for the
      paraganglioma probability with CE-MRA (nonweighted kappa, 0.67-0.77), whereas
      there was fair-to-good interobserver agreement with conventional MR imaging
      (nonweighted kappa, 0.50-0.65). CONCLUSION: In combination with conventional MR
      imaging, CE-MRA yields an excellent diagnostic value for the assessment of head
      and neck paragangliomas; hence, the 2 techniques should be regarded as
      complementary.

PMID- 18339725
TI  - Assessment of craniospinal arteriovenous malformations at 3T with highly
      temporally and highly spatially resolved contrast-enhanced MR angiography.
AB  - BACKGROUND AND PURPOSE: Patients with arteriovenous malformation (AVM) are known
      to have an elevated risk of complications with conventional catheter angiography
      (CCA) but nonetheless require monitoring of hemodynamics. Thus, we aimed to
      evaluate both anatomy and hemodynamics in patients with AVM noninvasively by
      using contrast-enhanced MR angiography (CE-MRA) at 3T and to compare the results
      with CCA. MATERIALS AND METHODS: Institutional review board approval and informed
      consent were obtained for this Health Insurance Portability and Accountability
      Act-compliant study. Twenty control subjects without vascular malformation (6
      men, 18-70 years of age) and 10 patients with AVMs (6 men, 20-74 years of age)
      underwent supra-aortic time-resolved and high-spatial-resolution CE-MRA at 3T.
      Large-field-of-view coronal acquisitions extending from the root of the aorta to
      the cranial vertex were obtained for both MRA techniques. Image quality was
      assessed by 2 specialized radiologists by using a 4-point scale. AVM
      characteristics and nidus size were evaluated by using both CE-MRA and CCA in all
      patients. RESULTS: In patients, 96.6% (319/330) of arterial segments on high
      spatial-resolution MRA and 87.7% (272/310) of arterial segments on time-resolved
      MRA were graded excellent/good. MRA showed 100% specificity for detecting feeding
      arteries and venous drainage (n = 8) and complete obliteration of the AVM in 2
      cases (concordance with CCA). Nidus diameters measured by both MRA and CCA
      resulted in a very strong correlation (r = 0.99) with a mild overestimation by
      MRA (0.10 cm by using the Bland-Altman plot). CONCLUSION: By combining highly
      temporally resolved and highly spatially resolved MRA at 3T as complementary
      studies, one can assess vascular anatomy and hemodynamics noninvasively in
      patients with AVM.

PMID- 18339726
TI  - Quantitative differentiation between healthy and disordered brain matter in
      patients with neurofibromatosis type I using diffusion tensor imaging.
AB  - BACKGROUND AND PURPOSE: Hyperintensities on T2-weighted images are seen in the
      brains of most patients with neurofibromatosis type I (NF-1), but the origin of
      these unidentified bright objects (UBOs) remains obscure. In the current study,
      we examined the diffusion characteristics of brain tissue in children with NF-1
      to test the hypothesis that a microstructural abnormality is present in NF-1.
      MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was performed in 50
      children with NF-1 and 8 controls. Circular regions of interest were manually
      placed in 7 standardized locations in both hemispheres, including UBO sites.
      Apparent diffusion coefficients (ADC), fractional anisotropy (FA), and axial
      anisotropy (A(m)) were used to differentiate quantitatively between healthy and
      disordered brain matter. Differences in eigenvalues (lambda(1), lambda(2),
      lambda(3)) were determined to examine parenchymal integrity. RESULTS: We found
      higher ADC values for UBOs than for normal-appearing sites (P < .01) and higher
      ADC values for normal-appearing sites than for controls (P < .04 in 5 of 7
      regions). In most regions, we found no differences in FA or A(m). Eigenvalues
      lambda(2) and lambda(3) were higher at UBO sites than in normal-appearing sites
      (P < .04). CONCLUSION: With ADC, it was possible to differentiate quantitatively
      between normal- and abnormal-appearing brain matter in NF-1 and also between
      normal-appearing brain matter in NF-1 and healthy brain matter in controls,
      indicating subtle pathologic damage disrupting the tissue microstructure in the
      NF-1 brain. Higher diffusivity for lambda(1), lambda(2), and lambda(3) indicates
      that this disturbance of microstructure is caused by accumulation of fluid or
      vacuolation.

PMID- 18339727
TI  - Pilot randomised controlled trial of occupational therapy to optimise
      independence in Parkinson's disease: the PD OT trial.
AB  - OBJECTIVE: To perform a pilot trial of occupational therapy (OT) to optimise
      functional independence in Parkinson disease (PD) to assess accrual/withdrawal
      rates, acceptability, outcome measures, and inform sample-size calculation.
      METHOD: Non-demented patients with idiopathic PD and difficulties with activities
      of daily living (ADL) were recruited provided they had not received OT in the
      last 2 years and/or physiotherapy in the last year. Patients were randomised to
      immediate OT or OT after completion of the trial. Patients randomised to OT were
      assessed at home by an experienced therapist and then received six home treatment
      sessions over 2 months. Interventions were targeted at functional independence
      and mobility goals. Outcome measures were: Nottingham Extended Activity of Daily
      Living Scale, Rivermead Mobility Index, Unified Parkinson's Disease Rating Scale
      ADL scale, Parkinson's Disease Questionnaire 39, EuroQol-EQ-5D, Hospital Anxiety
      and Depression Scale, and health economics analysis. RESULTS: 39 patients (25
      male; mean age 73 years) were recruited from four centres over 16 months. The
      mean difference in NEADL at 8 months was 3.5 (95% CI -3.2 to 10.2). The mean
      difference in PDQ-39 Summary Score was 3.8 (95% CI -4.94 to 12.6). There were
      strong correlations between the PDQ-39 and other outcomes. The intervention was
      acceptable to patients, with a low withdrawal rate and good questionnaire
      completion. CONCLUSION: Randomisation to a trial of OT in PD is feasible. NEADL
      and PDQ-39 are relevant outcomes and provided data to inform sample size for an
      adequately powered randomised trial for which there is pressing need.

PMID- 18339728
TI  - Ganglioside complexes containing GQ1b as targets in Miller Fisher and Guillain
      Barre syndromes.
AB  - BACKGROUND: Serum antibodies to GQ1b are associated with Miller Fisher syndrome
      (MFS) and Guillain-Barre syndrome (GBS) with ophthalmoplegia. Antibodies to
      ganglioside complexes (GSCs) have not yet been examined in a large population of
      patients with MFS or GBS. This study aimed to determine the clinical significance
      of antibodies to GSCs in MFS and GBS. METHODS: The study investigated serum anti
      GSC antibodies and the clinical features in 64 MFS patients, 53 GBS patients with
      ophthalmoplegia (GBS-OP(+)) and 53 GBS patients without ophthalmoplegia (GBS-OP(
      )). RESULTS: Thirty patients with MFS (47%), 25 with GBS-OP(+) (47%) and none
      with GBS-OP(-) had antibodies to GSCs containing GQ1b or GT1a. Patients with MFS
      and GBS-OP(+) were subdivided according to the antibody reactivities; patients
      with antibodies specific to GQ1b and/or GT1a (without anti-GSCs antibodies) were
      placed in Group 1, those with antibodies against GSCs with a total of two sialic
      acids in the terminal residues, such as GQ1b/GM1, were placed in Group 2, and
      those with antibodies against GSCs with a total of three sialic acids in the
      terminal residue, such as GQ1b/GD1a, were placed in Group 3. In MFS, sensory
      disturbances were infrequent in Group 2 compared with the other groups
      (p<0.0001). Antibodies specific to GQ1b were observed more often in MFS than in
      GBS-OP(+) (p = 0.0002). CONCLUSIONS: IgG antibodies to GSCs containing GQ1b or
      GT1a were closely associated with the development of ophthalmoplegia in GBS, as
      well as MFS. Both GQ1b and clustered epitopes of GSCs containing GQ1b or GT1a may
      be prime target antigens for MFS and GBS-OP(+).

PMID- 18339729
TI  - Cognitive impairment in multiple sclerosis can be predicted by imaging early in
      the disease.
AB  - BACKGROUND: Cognitive impairment is common in multiple sclerosis (MS) and adds
      significantly to the burden of the disease. The ability to predict future
      cognitive impairment from imaging obtained at disease onset has not been
      investigated. METHODS: 62 patients imaged within 3 months of a clinically
      isolated syndrome were assessed neuropsychologically 7 years later. Baseline and
      periodic MRI measures of lesions, atrophy and normal-appearing white and grey
      matter were regressed against neuropsychological scores to explore the best
      predictors of cognitive outcome. RESULTS: 28 patients had developed clinically
      definite MS at follow-up and a further nine met revised McDonald criteria for MS.
      Deficits in speed of information processing and executive function were the most
      common abnormalities. Poor performance correlated with high anxiety ratings.
      Baseline T(1) lesion metrics predicted executive deficits, and new T(2) lesions
      at the 3-month follow-up predicted slowed information processing. An increase in
      myo-inositol concentration in normal-appearing white matter over the first 3
      years was associated with poor executive function. CONCLUSIONS: MRI variables
      obtained at the onset of a clinically isolated syndrome can predict future
      development of cognitive abnormalities. Our findings may have implications in
      monitoring and treating patients.

PMID- 18339730
TI  - Long-term outcome in patients with critical illness myopathy or neuropathy: the
      Italian multicentre CRIMYNE study.
AB  - BACKGROUND: Critical illness myopathy (CIM) and polyneuropathy (CIP), alone or in
      combination (CIP/CIM), are frequent complications in patients in the intensive
      care unit (ICU). There is no evidence that differentiating between CIP and CIM
      has any impact on patient prognosis. METHODS: 1-year prospective cohort study of
      patients developing CIP, CIM or combined CIP and CIM during ICU stay. RESULTS: 28
      out of 92 (30.4%) patients developed electrophysiological signs of CIP and/or CIM
      during their ICU stay, which persisted in 18 patients at ICU discharge. At
      hospital discharge, diagnoses in the 15 survivors were CIM in six cases, CIP in
      four, combined CIP and CIM in three and undetermined in two uncooperative
      patients. During the 1-year follow-up of six patients with CIM, one patient died
      and five recovered completely within 3 (three patients) to 6 (two patients)
      months. Of three patients with CIP/CIM, one died, one recovered and one with
      residual CIP remained tetraplegic. Of four patients with CIP, one recovered, two
      had persisting muscle weakness and one remained tetraparetic. CONCLUSION: CIM has
      a better prognosis than CIP. Differential diagnosis is important to predict long
      term outcome in ICU patients.

PMID- 18339731
TI  - The prevalence of essential tremor in rural northern Tanzania.
AB  - INTRODUCTION: Estimates of the prevalence of essential tremor (ET) vary widely
      but there are few existing data on the prevalence of ET in sub-Saharan Africa.
      PATIENTS AND METHODS: A door-to-door community based prevalence study of ET was
      carried out in the Hai district of northern Tanzania (n = 161,071). The screening
      questionnaire was followed by examination of positive responders and backed up
      with other case finding methods. RESULTS: 222 patients responded positively to
      the screening questions and 43 were referred by village elders. 65 (38 men, 27
      women) were diagnosed with ET. Mean age was 72 years and mean duration of
      symptoms was 11.3 years. The crude prevalence rate was 41/100,000 and age
      standardised prevalence compared with the UK population (2001) was 82/100,000.
      DISCUSSION: This is the first community based prevalence study of ET in sub
      Saharan Africa. Previous data from community based neurological surveys showed
      lower prevalence rates of 5/100,000 in Ethiopia and 10/100,000 in Nigeria. Non
      selective beta blockers are available locally and are affordable, yet none of
      these patients had previously been on any treatment.

PMID- 18339732
TI  - Two-crystal structures of tropomyosin C-terminal fragment 176-273: exposure of
      the hydrophobic core to the solvent destabilizes the tropomyosin molecule.
AB  - Tropomyosin (Tm) is a two-stranded alpha-helical coiled-coil protein, and when
      associated with troponin, it is responsible for the actin filament-based
      regulation of muscle contraction in vertebrate skeletal and cardiac muscles. It
      is widely believed that Tm adopts a flexible rod-like structure in which the
      flexibility must play a crucial role in its functions. To obtain more information
      about the flexibility of Tm, we solved and compared two crystal structures of the
      identical C-terminal segments, spanning approximately 40% of the entire length.
      We also compared these structures with our previously reported crystal structure
      of an almost identical Tm segment in a distinct crystal form. The parameters
      specifying the local coiled-coil geometry, such as the separation between two
      helices and the local helical pitch, undulate along the length of Tm in the same
      way as among the three crystal structures, indicating that these parameters are
      defined by the amino acid sequence. In the region of increased separation, around
      Glu-218 and Gln-263, the hydrophobic core is disrupted by three holes. Moreover,
      for the first time to our knowledge, for Tm, water molecules have been identified
      in these holes. In some structures, the B-factors are higher around the holes
      than in the rest of the molecule. The Tm coiled-coil must be destabilized and
      therefore may be flexible, not only in the alanine clusters but also in the
      regions of the broken core. A closer look at the local staggering between the two
      chains and the local bending revealed that the strain accumulates at the alanine
      cluster and may be relaxed in the broken core region. Moreover, the strain is
      distributed over a long range, even when a deformation like bending may occur at
      a limited number of spots. Thus, Tm should not be regarded as a train of short
      rigid rods connected by flexible linkers, but rather as a seamless rubber rod
      patched with relatively more flexible regions.

PMID- 18339733
TI  - Molecular force balance measurements reveal that double-stranded DNA unbinds
      under force in rate-dependent pathways.
AB  - Strand separation of double-stranded DNA is a crucial step for essential cellular
      processes such as recombination and transcription. By means of a molecular force
      balance, we have analyzed the impact of different pulling directions and
      different force-loading rates on the unbinding process of short double-stranded
      DNA. At loading rates above 9 x 10(5) pN/s, we found a marked difference in
      rupture probability for pulling the duplex in 3'-3' direction compared to a 5'-5'
      direction, indicating different unbinding pathways. We propose a mechanism by
      which unbinding at low loading rates is dominated by nondirectional thermal
      fluctuations, whereas mechanical properties of the DNA become more important at
      high loading rates and reveal the asymmetry of the phosphoribose backbone. Our
      model explains the difference of 3'-3' and 5'-5' unbinding as a kinetic process,
      where the loading rate exceeds the relaxation time of DNA melting bubbles.

PMID- 18339734
TI  - Fluorescent N-arylaminonaphthalene sulfonate probes for amyloid aggregation of
      alpha-synuclein.
AB  - The deposition of fibrillar structures (amyloids) is characteristic of
      pathological conditions including Alzheimer's and Parkinson's diseases. The
      detection of protein deposits and the evaluation of their kinetics of aggregation
      are generally based on fluorescent probes such as thioflavin T and Congo red. In
      a search for improved fluorescence tools for studying amyloid formation, we
      explored the ability of N-arylaminonaphthalene sulfonate (NAS) derivatives to act
      as noncovalent probes of alpha-synuclein (AS) fibrillation, a process linked to
      Parkinson's disease and other neurodegenerative disorders. The compounds bound to
      fibrillar AS with micromolar K(d)s, and exhibited fluorescence enhancement,
      hyperchromism, and high anisotropy. We conclude that the probes experience a
      hydrophobic environment and/or restricted motion in a polar region. Time- and
      spectrally resolved emission intensity and anisotropy provided further
      information regarding structural features of the protein and the dynamics of
      solvent relaxation. The steady-state and time-resolved parameters changed during
      the course of aggregation. Compared with thioflavin T, NAS derivatives constitute
      more sensitive and versatile probes for AS aggregation, and in the case of bis
      NAS detect oligomeric as well as fibrillar species. They can function in
      convenient, continuous assays, thereby providing useful tools for studying the
      mechanisms of amyloid formation and for high-throughput screening of factors
      inhibiting and/or reversing protein aggregation in neurodegenerative diseases.

PMID- 18339735
TI  - Role of tryptophan residues in gramicidin channel organization and function.
AB  - The linear peptide gramicidin forms prototypical ion channels specific for
      monovalent cations and has been used extensively to study the organization,
      dynamics, and function of membrane-spanning channels. The tryptophan residues in
      gramicidin channels are crucial for maintaining the structure and function of the
      channel. We explored the structural basis for the reduction in channel
      conductance in the case of single-tryptophan analogs of gramicidin with three Trp
      --> hydrophobic substitutions using a combination of fluorescence approaches,
      which include red edge excitation shift and membrane penetration depth analysis,
      size-exclusion chromatography, and circular dichroism spectroscopy. We show here
      that the gramicidin analogs containing single-tryptophan residues adopt a mixture
      of nonchannel and channel conformations, as evident from analysis of membrane
      penetration depth, size-exclusion chromatography, and backbone circular dichroism
      data. These results are potentially useful in analyzing the effect of tryptophan
      substitution on the functioning of other ion channels and membrane proteins.

PMID- 18339736
TI  - Spectroscopic properties of reaction center pigments in photosystem II core
      complexes: revision of the multimer model.
AB  - Absorbance difference spectra associated with the light-induced formation of
      functional states in photosystem II core complexes from Thermosynechococcus
      elongatus and Synechocystis sp. PCC 6803 (e.g., P(+)Pheo(-),P(+)Q(A)(-),(3)P) are
      described quantitatively in the framework of exciton theory. In addition, effects
      are analyzed of site-directed mutations of D1-His(198), the axial ligand of the
      special-pair chlorophyll P(D1), and D1-Thr(179), an amino-acid residue nearest to
      the accessory chlorophyll Chl(D1), on the spectral properties of the reaction
      center pigments. Using pigment transition energies (site energies) determined
      previously from independent experiments on D1-D2-cytb559 complexes, good
      agreement between calculated and experimental spectra is obtained. The only
      difference in site energies of the reaction center pigments in D1-D2-cytb559 and
      photosystem II core complexes concerns Chl(D1). Compared to isolated reaction
      centers, the site energy of Chl(D1) is red-shifted by 4 nm and less
      inhomogeneously distributed in core complexes. The site energies cause primary
      electron transfer at cryogenic temperatures to be initiated by an excited state
      that is strongly localized on Chl(D1) rather than from a delocalized state as
      assumed in the previously described multimer model. This result is consistent
      with earlier experimental data on special-pair mutants and with our previous
      calculations on D1-D2-cytb559 complexes. The calculations show that at 5 K the
      lowest excited state of the reaction center is lower by approximately 10 nm than
      the low-energy exciton state of the two special-pair chlorophylls P(D1) and P(D2)
      which form an excitonic dimer. The experimental temperature dependence of the
      wild-type difference spectra can only be understood in this model if temperature
      dependent site energies are assumed for Chl(D1) and P(D1), reducing the above
      energy gap from 10 to 6 nm upon increasing the temperature from 5 to 300 K. At
      physiological temperature, there are considerable contributions from all pigments
      to the equilibrated excited state P*. The contribution of Chl(D1) is twice that
      of P(D1) at ambient temperature, making it likely that the primary charge
      separation will be initiated by Chl(D1) under these conditions. The calculations
      of absorbance difference spectra provide independent evidence that after primary
      electron transfer the hole stabilizes at P(D1), and that the physiologically
      dangerous charge recombination triplets, which may form under light stress,
      equilibrate between Chl(D1) and P(D1).

PMID- 18339737
TI  - Both MHC class II and its GPI-anchored form undergo hop diffusion as observed by
      single-molecule tracking.
AB  - Previously, investigations using single-fluorescent-molecule tracking at frame
      rates of up to 65 Hz, showed that the transmembrane MHC class II protein and its
      GPI-anchored modified form expressed in CHO cells undergo simple Brownian
      diffusion, without any influence of actin depolymerization with cytochalasin D.
      These results are at apparent variance with the view that GPI-anchored proteins
      stay with cholesterol-enriched raft domains, as well as with the observation that
      both lipids and transmembrane proteins undergo short-term confined diffusion
      within a compartment and long-term hop diffusion between compartments. Here, this
      apparent discrepancy has been resolved by reexamining the same paradigm, by using
      both high-speed single-particle tracking (50 kHz) and single fluorescent-molecule
      tracking (30 Hz). Both molecules exhibited rapid hop diffusion between 40-nm
      compartments, with an average dwell time of 1-3 ms in each compartment.
      Cytochalasin D hardly affected the hop diffusion, consistent with previous
      observations, whereas latrunculin A increased the compartment sizes with
      concomitant decreases of the hop rates, which led to an approximately 50%
      increase in the median macroscopic diffusion coefficient. These results indicate
      that the actin-based membrane skeleton influences the diffusion of both
      transmembrane and GPI-anchored proteins.

PMID- 18339738
TI  - A biophysically based mathematical model of unitary potential activity in
      interstitial cells of Cajal.
AB  - Unitary potential (UP) depolarizations are the basic intracellular events
      responsible for pacemaker activity in interstitial cells of Cajal (ICCs), and are
      generated at intracellular sites termed "pacemaker units". In this study, we
      present a mathematical model of the transmembrane ion flows and intracellular
      Ca(2+) dynamics from a single ICC pacemaker unit acting at near-resting membrane
      potential. This model quantitatively formalizes the framework of a novel ICC
      pacemaking mechanism that has recently been proposed. Model simulations produce
      spontaneously rhythmic UP depolarizations with an amplitude of approximately 3 mV
      at a frequency of 0.05 Hz. The model predicts that the main inward currents,
      carried by a Ca(2+)-inhibited nonselective cation conductance, are activated by
      depletion of sub-plasma-membrane [Ca(2+)] caused by sarcoendoplasmic reticulum
      calcium ATPase Ca(2+) sequestration. Furthermore, pacemaker activity predicted by
      our model persists under simulated voltage clamp and is independent of [IP(3)]
      oscillations. The model presented here provides a basis to quantitatively analyze
      UP depolarizations and the biophysical mechanisms underlying their production.

PMID- 18339739
TI  - Elasticity, strength, and water permeability of bilayers that contain raft
      microdomain-forming lipids.
AB  - Bilayers composed of phosphatidylcholine (PC), sphingomyelin (SM), and
      cholesterol (CHOL) are commonly used as systems to model the raft-lipid domain
      structure believed to compartmentalize particular cell membrane proteins. In this
      work, micropipette aspiration of giant unilamellar vesicles was used to test the
      elasticities, water permeabilities, and rupture tensions of single-component PC,
      binary 1:1 PC/CHOL, and 1:1 SM/CHOL, and ternary 1:1:1 PC/SM/CHOL bilayers, one
      set of measurements with dioleoyl PC (DOPC; C18:1/C18:1 PC) and the other with
      stearoyloleoyl PC (SOPC; C18:0/C18:1 PC). Defining the elastic moduli (K(A)), the
      initial slopes of the increase in tension (sigma) versus stretch in lipid surface
      area (alpha(e)) were determined for all systems at low (15 degrees C) and high
      (32-33 degrees C) temperatures. The moduli for the single-component PC and binary
      phospholipid/CHOL bilayers followed a descending hierarchy of stretch resistance
      with SM/CHOL > SOPC/CHOL > DOPC/CHOL > PC. Although much more resistant to
      stretch than the single-component PC bilayers, the elastic response of vesicle
      bilayers made from the ternary phospholipid/CHOL mixtures showed an abrupt
      softening (discontinuity in slope), when immediately subjected to a steady ramp
      of tension at the low temperature (15 degrees C). However, the discontinuities in
      elastic stretch resistance at low temperature vanished when the bilayers were
      held at approximately 1 mN/m prestress for long times before a tension ramp and
      when tested at the higher temperature 32-33 degrees C. The elastic moduli of
      single-component PC and DOPC/CHOL bilayers changed very little with temperature,
      whereas the moduli of the binary SOPC/CHOL and SM/CHOL bilayers diminished
      markedly with increase in temperature, as did the ternary SOPC/SM/CHOL system.
      For all systems, increasing temperature increased the water permeability but
      decreased rupture tension. Concomitantly, the measurements of permeability
      exhibited a prominent correlation with the rupture tension across all the
      systems. Together, these micromechanical tests of binary and ternary
      phospholipid/CHOL bilayers demonstrate that PC hydrocarbon chain unsaturation and
      temperature are major determinants of the mechanical and permeation properties of
      membranes composed of raft microdomain-forming lipids.

PMID- 18339740
TI  - Direct visualization of spruce budworm antifreeze protein interacting with ice
      crystals: basal plane affinity confers hyperactivity.
AB  - Antifreeze proteins (AFPs) protect certain organisms from freezing by adhering to
      ice crystals, thereby preventing their growth. All AFPs depress the
      nonequilibrium freezing temperature below the melting point; however AFPs from
      overwintering insects, such as the spruce budworm (sbw) are 10-100 times more
      effective than most fish AFPs. It has been proposed that the exceptional activity
      of these AFPs depends on their ability to prevent ice growth at the basal plane.
      To test the hypothesis that the hyperactivity of sbwAFP results from direct
      affinity to the basal plane, we fluorescently tagged sbwAFP and visualized it on
      the surface of ice crystals using fluorescence microscopy. SbwAFP accumulated at
      the six prism plane corners and the two basal planes of hexagonal ice crystals.
      In contrast, fluorescently tagged fish type III AFP did not adhere to the basal
      planes of a single-crystal ice hemisphere. When ice crystals were grown in the
      presence of a mixture of type III AFP and sbwAFP, a hybrid crystal shape was
      produced with sbwAFP bound to the basal planes of truncated bipyramidal crystals.
      These observations are consistent with the blockage of c-axial growth of ice as a
      result of direct interaction of sbwAFP with the basal planes.

PMID- 18339741
TI  - Effects on membrane capacitance of steroids with antagonist properties at GABAA
      receptors.
AB  - We investigated the electrophysiological signature of neuroactive steroid
      interactions with the plasma membrane. We found that charged, sulfated
      neuroactive steroids, those that exhibit noncompetitive antagonism of GABA(A)
      receptors, altered capacitive charge movement in response to voltage pulses in
      cells lacking GABA receptors. Uncharged steroids, some of which are potent
      enhancers of GABA(A) receptor activity, produced no alteration in membrane
      capacitance. We hypothesized that the charge movements might result from physical
      translocation of the charged steroid through the transmembrane voltage, as has
      been observed previously with several hydrophobic anions. However, the charge
      movements and relaxation time constants of capacitive currents did not exhibit
      the Boltzmann-type voltage dependence predicted by a single barrier model.
      Further, a fluorescently tagged analog of a sulfated neurosteroid altered
      membrane capacitance similar to the parent compound but produced no voltage
      dependent fluorescence change, a result inconsistent with a strong change in the
      polar environment of the fluorophore during depolarization. These findings
      suggest that negatively charged sulfated steroids alter the plasma membrane
      capacitance without physical movement of the molecule through the electric field.

PMID- 18339742
TI  - Docosahexaenoic acid enhances segregation of lipids between : 2H-NMR study.
AB  - Solid-state (2)H-NMR of [(2)H(31)]-N-palmitoylsphingomyelin ([(2)H(31)]16:0SM,
      PSM*), supplemented by differential scanning calorimetry, was used for the first
      time, to our knowledge, to investigate the molecular organization of the
      sphingolipid in 1:1:1 mol mixtures with 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphoethanolamine (16:0-18:1PE, POPE) or 1-palmitoyl-2-docosahexaenoyl-sn
      glycero-3-phosphoethanolamine (16:0-22:6PE, PDPE) and cholesterol. When compared
      with (2)H-NMR data for analogous mixtures of [(2)H(31)]16:0-18:1PE (POPE*) or
      [(2)H(31)]16:0-22:6PE (PDPE*) with egg SM and cholesterol, molecular interactions
      of oleic acid (OA) versus docosahexaenoic acid (DHA) are distinguished, and
      details of membrane architecture emerge. SM-rich, characterized by higher-order,
      and PE-rich, characterized by lower-order, domains <20 nm in size are formed in
      the absence and presence of cholesterol in both OA- and DHA-containing membranes.
      Although acyl chain order within both domains increases on the addition of sterol
      to the two systems, the resultant differential in order between SM- and PE-rich
      domains is almost a factor of 3 greater with DHA than with OA. Our interpretation
      is that the aversion that cholesterol has for DHA--but not for OA--excludes the
      sterol from DHA-containing, PE-rich (nonraft) domains and excludes DHA from SM
      rich/cholesterol-rich (raft) domains. We attribute, in part, the diverse health
      benefits associated with dietary consumption of DHA to an alteration in membrane
      domains.

PMID- 18339743
TI  - Mono- and trivalent ions around DNA: a small-angle scattering study of
      competition and interactions.
AB  - The presence of small numbers of multivalent ions in DNA-containing solutions
      results in strong attractive forces between DNA strands. Despite the biological
      importance of this interaction, e.g., DNA condensation, its physical origin
      remains elusive. We carried out a series of experiments to probe interactions
      between short DNA strands as small numbers of trivalent ions are included in a
      solution containing DNA and monovalent ions. Using resonant (anomalous) and
      nonresonant small angle x-ray scattering, we coordinated measurements of the
      number and distribution of each ion species around the DNA with the onset of
      attractive forces between DNA strands. DNA-DNA interactions occur as the number
      of trivalent ions increases. Surprisingly good agreement is found between data
      and size-corrected numerical Poisson-Boltzmann predictions of ion competition for
      non- and weakly interacting DNAs. We also obtained an estimate for the minimum
      number of trivalent ions needed to initiate DNA-DNA attraction.

PMID- 18339744
TI  - Femtosecond spectroscopy of native and carotenoidless purple-bacterial LH2
      clarifies functions of carotenoids.
AB  - EET between the two circular bacteriochlorophyll compartments B800 and B850 in
      native (containing the carotenoid rhodopin) and carotenoidless LH2 isolated from
      the photosynthetic purple sulfur bacterium Allochromatium minutissimum was
      investigated by femtosecond time-resolved transient absorption spectroscopy. Both
      samples were excited with 120-fs laser pulses at 800 nm, and spectral evolution
      was followed in the 720-955 nm range at different delay times. No dependence of
      transient absorption in the B800 band on the presence of the carotenoid rhodopin
      was found. Together with the likewise virtually unchanged absorption spectra in
      the bacteriochlorophyll Q(y) region, these observations suggest that absence of
      rhodopin does not significantly alter the structure of the pigment-protein
      complex including interactions between bacteriochlorophylls. Apparently, rhodopin
      does also not accelerate B800 to B850 EET in LH2, contrary to what has been
      suggested previously. Moreover, "carotenoid-catalyzed internal conversion" can
      also be excluded for the bacteriochlorophylls in LH2 of A. minutissimum. Together
      with previous results obtained with two-photon fluorescence excitation
      spectroscopy, it can also be concluded that there is neither EET from rhodopin to
      B800 nor (back-)EET from B800 to rhodopin.

PMID- 18339745
TI  - Subunit-specific effect of the voltage sensor domain on Ca2+ sensitivity of BK
      channels.
AB  - Large conductance Ca(2+)- and voltage-activated K(+) (BK) channels, composed of
      pore-forming alpha-subunits and auxiliary beta-subunits, play important roles in
      diverse physiological processes. The differences in BK channel phenotypes are
      primarily due to the tissue-specific expression of beta-subunits (beta1-beta4)
      that modulate channel function differently. Yet, the molecular basis of the
      subunit-specific regulation is not clear. In our study, we demonstrate that
      perturbation of the voltage sensor in BK channels by mutations selectively
      disrupts the ability of the beta1-subunit--but not that of the beta2-subunit--to
      enhance apparent Ca(2+) sensitivity. These mutations change the number of
      equivalent gating charges, the voltage dependence of voltage sensor movements,
      the open-close equilibrium of the channel, and the allosteric coupling between
      voltage sensor movements and channel opening to various degrees, indicating that
      they alter the conformation and movements of the voltage sensor and the
      activation gate. Similarly, the ability of the beta1-subunit to enhance apparent
      Ca(2+) sensitivity is diminished to various degrees, correlating quantitatively
      with the shift of voltage dependence of voltage sensor movements. In contrast,
      none of these mutations significantly reduces the ability of the beta2-subunit to
      enhance Ca(2+) sensitivity. These results suggest that the beta1-subunit enhances
      Ca(2+) sensitivity by altering the conformation and movements of the voltage
      sensor, whereas the similar function of the beta2-subunit is governed by a
      distinct mechanism.

PMID- 18339746
TI  - Conformation, length, and speed measurements of electrodynamically stretched DNA
      in nanochannels.
AB  - A method is presented to rapidly and precisely measure the conformation, length,
      speed, and fluorescence intensity of single DNA molecules constrained by a
      nanochannel. DNA molecules were driven electrophoretically from a nanoslit into a
      nanochannel to confine and dynamically elongate them beyond their equilibrium
      length for repeated detection via laser-induced fluorescence spectroscopy. A
      single-molecule analysis algorithm was developed to analytically model bursts of
      fluorescence and determine the folding conformation of each stretched molecule.
      This technique achieved a molecular length resolution of 114 nm and an analysis
      time of around 20 ms per molecule, which enabled the sensitive investigation of
      several aspects of the physical behavior of DNA in a nanochannel. lambda
      bacteriophage DNA was used to study the dependence of stretching on the applied
      device bias, the effect of conformation on speed, and the amount of DNA
      fragmentation in the device. A mixture of lambda-bacteriophage with the fragments
      of its own HindIII digest, a standard DNA ladder, was sized by length as well as
      by fluorescence intensity, which also allowed the characterization of DNA speed
      in a nanochannel as a function of length over two and a half orders of magnitude.

PMID- 18339747
TI  - Hydration dependence of active core fluctuations in bacteriorhodopsin.
AB  - We used neutron scattering and specific hydrogen-deuterium labeling to
      investigate the thermal dynamics of isotope-labeled amino acids and retinal,
      predominantly in the active core and extracellular moiety of bacteriorhodopsin
      (BR) in the purple membrane and the dynamical response to hydration. Measurements
      on two neutron spectrometers allowed two populations of motions to be
      characterized. The lower amplitude motions were found to be the same for both the
      labeled amino acids and retinal of BR and the global membrane. The larger
      amplitude dynamics of the labeled part, however, were found to be more resilient
      than the average membrane, suggesting their functional importance. The response
      to hydration was characterized, showing that the labeled part of BR is not
      shielded from hydration effects. The results suggest that the inhibition of high
      amplitude motions by lowering hydration may play a key role in the slowing down
      of the photocycle and the proton pumping activity of BR.

PMID- 18339748
TI  - Ten-microsecond molecular dynamics simulation of a fast-folding WW domain.
AB  - All-atom molecular dynamics (MD) simulations of protein folding allow analysis of
      the folding process at an unprecedented level of detail. Unfortunately, such
      simulations have not yet reached their full potential both due to difficulties in
      sufficiently sampling the microsecond timescales needed for folding, and because
      the force field used may yield neither the correct dynamical sequence of events
      nor the folded structure. The ongoing study of protein folding through
      computational methods thus requires both improvements in the performance of
      molecular dynamics programs to make longer timescales accessible, and testing of
      force fields in the context of folding simulations. We report a ten-microsecond
      simulation of an incipient downhill-folding WW domain mutant along with
      measurement of a molecular time and activated folding time of 1.5 microseconds
      and 13.3 microseconds, respectively. The protein simulated in explicit solvent
      exhibits several metastable states with incorrect topology and does not assume
      the native state during the present simulations.

PMID- 18339749
TI  - Amyloid-type fiber formation in control of enzyme action: interfacial activation
      of phospholipase A2.
AB  - The lag-burst behavior in the action of phospholipase A(2) (PLA(2)) on 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine was investigated at temperatures slightly
      offset from the main phase transition temperature T(m) of this lipid, thus
      slowing down the kinetics of the activation process. Distinct stages leading to
      maximal activity were resolved using a combination of fluorescence parameters,
      including Forster resonance energy transfer between donor- and acceptor-labeled
      enzyme, fluorescence anisotropy, and lifetime, as well as thioflavin T
      fluorescence enhancement. We showed that the interfacial activation of PLA(2),
      evident after the preceding lag phase, coincides with the formation of oligomers
      staining with thioflavin T and subsequently with Congo red. Based on previous
      studies and our findings here, we propose a novel mechanism for the control of
      PLA(2), involving amyloid protofibrils with highly augmented enzymatic activity.
      Subsequently, these protofibrils form "mature" fibrils, devoid of activity.
      Accordingly, the process of amyloid formation is used as an on-off switch to
      obtain a transient burst in enzymatic catalysis.

PMID- 18339750
TI  - "Shimmying like my sister" cell.

PMID- 18339751
TI  - Nonequilibrium single molecule protein folding in a coaxial mixer.
AB  - We have developed a continuous-flow mixing device suitable for monitoring
      bioconformational reactions at the single-molecule level with a response time of
      approximately 10 ms under single-molecule flow conditions. Its coaxial geometry
      allows three-dimensional hydrodynamic focusing of sample fluids to diffraction
      limited dimensions where diffusional mixing is rapid and efficient. The capillary
      based design enables rapid in-lab construction of mixers without the need for
      expensive lithography-based microfabrication facilities. In-line filtering of
      sample fluids using granulated silica particles virtually eliminates clogging and
      extends the lifetime of each device to many months. In this article, to determine
      both the distance-to-time transfer function and the instrument response function
      of the device we characterize its fluid flow and mixing properties using both
      fluorescence cross-correlation spectroscopy velocimetry and finite element fluid
      dynamics simulations. We then apply the mixer to single molecule FRET protein
      folding studies of Chymotrypsin Inhibitor protein 2. By transiently populating
      the unfolded state of Chymotrypsin Inhibitor Protein 2 (CI2) under nonequilibrium
      in vitro refolding conditions, we spatially and temporally resolve the denaturant
      dependent nonspecific collapse of the unfolded state from the barrier-limited
      folding transition of CI2. Our results are consistent with previous CI2 mixing
      results that found evidence for a heterogeneous unfolded state consisting of cis-
      and trans-proline conformers.

PMID- 18339752
TI  - Interaction of the most membranotropic region of the HCV E2 envelope glycoprotein
      with membranes. Biophysical characterization.
AB  - The previously identified membrane-active regions of the hepatitis C virus (HCV)
      E1 and E2 envelope glycoproteins led us to identify different segments that might
      be implicated in viral membrane fusion, membrane interaction, and/or protein
      protein binding. HCV E2 glycoprotein contains one of the most membranotropic
      segments, segment 603-634, which has been implicated in CD81 binding, E1/E2 and
      E2/E2 dimerization, and membrane interaction. Through a series of complementary
      experiments, we have carried out a study of the binding and interaction with the
      lipid bilayer of a peptide corresponding to segment 603-634, peptide E2(FP), as
      well as the structural changes induced by membrane binding that take place in
      both the peptide and the phospholipid molecules. Here, we demonstrate that
      peptide E2(FP) binds to and interacts with phospholipid model membranes,
      modulates the polymorphic phase behavior of membrane phospholipids, is localized
      in a shallow position in the membrane, and is probably oligomerized in the
      presence of membranes. These data support the role of E2(FP) in HCV-mediated
      membrane fusion, and sustain the notion that this segment of the E2 envelope
      glycoprotein, together with other segments of E2 and E1 glycoproteins, provides
      the driving force for the merging of the viral and target cell membranes.

PMID- 18339753
TI  - Urea and guanidinium chloride denature protein L in different ways in molecular
      dynamics simulations.
AB  - In performing protein-denaturation experiments, it is common to employ different
      kinds of denaturants interchangeably. We make use of molecular dynamics
      simulations of Protein L in water, in urea, and in guanidinium chloride (GdmCl)
      to ascertain if there are any structural differences in the associated unfolding
      processes. The simulation of proteins in solutions of GdmCl is complicated by the
      large number of charges involved, making it difficult to set up a realistic force
      field. Furthermore, at high concentrations of this denaturant, the motion of the
      solvent slows considerably. The simulations show that the unfolding mechanism
      depends on the denaturing agent: in urea the beta-sheet is destabilized first,
      whereas in GdmCl, it is the alpha-helix. Moreover, whereas urea interacts with
      the protein accumulating in the first solvation shell, GdmCl displays a longer
      range electrostatic effect that does not perturb the structure of the solvent
      close to the protein.

PMID- 18339754
TI  - Three-dimensional FRET reconstruction microscopy for analysis of dynamic
      molecular interactions in live cells.
AB  - Analysis of cellular pathways requires concentration measurements of dynamically
      interacting molecules within the three-dimensional (3D) space of single living
      cells. Forster resonance energy transfer (FRET) microscopy from widefield, from
      confocal, and potentially from superresolution microscopes can access this
      information; however, these measurements are distorted by the inherent 3D
      blurring of optical imaging, spectral overlap of fluorophores, and detection
      noise. We propose a mathematical model of these processes and demonstrate,
      through simulation, how these distortions limit the dynamic range and sensitivity
      of conventional FRET microscopy. Using this model, we devise and validate a new
      approach (called 3D-FRET stoichiometry reconstruction, 3DFSR) for reconstructing
      3D distributions of bound and free fluorescent molecules. Previous attempts to
      reconstruct 3D-FRET data relied on sequential spectral unmixing and
      deconvolution, a process that corrupts the detection statistics. We demonstrate
      that 3DFSR is superior to these approaches since it simultaneously models
      spectral mixing, optical blurring, and detection noise. To achieve the full
      potential of this technique, we developed an instrument capable of acquiring 3D
      FRET data rapidly and sensitively from single living cells. Compared with
      conventional FRET microscopy, our 3D-FRET reconstruction technique and new
      instrumentation provides orders of magnitude gains in both sensitivity and
      accuracy wherein sustained high-resolution four-dimensional (x,y,z,t) imaging of
      molecular interactions inside living cells was achieved. These results verify
      previous observations that Cdc42 signaling is localized to the advancing margins
      of forming phagosomes in macrophages.

PMID- 18339755
TI  - Lateral pressure dependence of the phospholipid transmembrane diffusion rate in
      planar-supported lipid bilayers.
AB  - The dependence of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) flip-flop
      kinetics on the lateral membrane pressure in a phospholipid bilayer was
      investigated by sum-frequency vibrational spectroscopy. Planar-supported lipid
      bilayers were prepared on fused silica supports using the Langmuir
      Blodgett/Langmuir-Schaeffer technique, which allows precise control over the
      lateral surface pressure and packing density of the membrane. The lipid bilayer
      deposition pressure was varied from 28 to 42 mN/m. The kinetics of lipid flip
      flop in these membranes was measured by sum-frequency vibrational spectroscopy at
      37 degrees C. An order-of-magnitude difference in the rate constant for lipid
      translocation (10.9 x 10(-4) s(-1) to 1.03 x 10(-4) s(-1)) was measured for
      membranes prepared at 28 mN/m and 42 mN/m, respectively. This change in rate
      results from only a 7.4% change in the packing density of the lipids in the
      bilayer. From the observed kinetics, the area of activation for native
      phospholipid flip-flop in a protein-free DPPC planar-supported lipid bilayer was
      determined to be 73 +/- 12 A(2)/molecule at 37 degrees C. Significance of the
      observed activation area and potential future applications of the technique to
      the study of phospholipid flip-flop are discussed.

PMID- 18339756
TI  - Role of gp120 trimerization on HIV binding elucidated with Brownian adhesive
      dynamics.
AB  - We simulated the docking of human immunodeficiency virus (HIV) with a cell
      membrane using Brownian adhesive dynamics. The main advance in the current
      version of Brownian adhesive dynamics is that we use a simple bead-spring model
      to coarsely approximate the role of gp120 trimerization on HIV docking. We used
      our simulations to elucidate the effect of env spike density on the rate and
      probability of HIV binding, as well as the probability that each individual gp120
      trimer is fully engaged. We found that for typical CD4 surface densities, viruses
      expressing as few as 8 env spikes will dock with binding rate constants
      comparable to viruses expressing 72 spikes. We investigated the role of cellular
      receptor diffusion on the degree of binding achieved by the virus on both short
      timescales (where binding has reached steady state but before substantial
      receptor accumulation in the viral-cell contact zone has occurred) and long
      timescales (where the system has reached steady state). On short timescales,
      viruses with 10-23 env trimers most efficiently form fully engaged trimers. On
      long timescales, all gp120 in the contact area will become bound to CD4. We found
      that it takes seconds for engaged trimers to cluster CD4 molecules in the contact
      zone, which partially explains the deleay in viral entry.

PMID- 18339757
TI  - Bayesian inference for improved single molecule fluorescence tracking.
AB  - Single molecule tracking is widely used to monitor the change in position of
      lipids and proteins in living cells. In many experiments in which molecules are
      tagged with a single or small number of fluorophores, the signal/noise ratio may
      be limiting, the number of molecules is not known, and fluorophore blinking and
      photobleaching can occur. All these factors make accurate tracking over long
      trajectories difficult and hence there is still a pressing need to develop better
      algorithms to extract the maximum information from a sequence of fluorescence
      images. We describe here a Bayesian-based inference approach, based on a trans
      dimensional sequential Monte Carlo method that utilizes both the spatial and
      temporal information present in the image sequences. We show, using model data,
      where the real trajectory of the molecule is known, that our method allows
      accurate tracking of molecules over long trajectories even with low signal/noise
      ratio and in the presence of fluorescence blinking and photobleaching. The method
      is then applied to real experimental data.

PMID- 18339758
TI  - Modeling the influence of the E-cadherin-beta-catenin pathway in cancer cell
      invasion: a multiscale approach.
AB  - In this article, we show, using a mathematical multiscale model, how cell
      adhesion may be regulated by interactions between E-cadherin and beta-catenin and
      how the control of cell adhesion may be related to cell migration, to the
      epithelial-mesenchymal transition and to invasion in populations of eukaryotic
      cells. E-cadherin mediates cell-cell adhesion and plays a critical role in the
      formation and maintenance of junctional contacts between cells. Loss of E
      cadherin-mediated adhesion is a key feature of the epithelial-mesenchymal
      transition. beta-catenin is an intracellular protein associated with the actin
      cytoskeleton of a cell. E-cadherins bind to beta-catenin to form a complex which
      can interact both with neighboring cells to form bonds, and with the cytoskeleton
      of the cell. When cells detach from one another, beta-catenin is released into
      the cytoplasm, targeted for degradation, and downregulated. In this process there
      are multiple protein-complexes involved which interact with beta-catenin and E
      cadherin. Within a mathematical individual-based multiscale model, we are able to
      explain experimentally observed patterns solely by a variation of cell-cell
      adhesive interactions. Implications for cell migration and cancer invasion are
      also discussed.

PMID- 18339759
TI  - Actin cytoskeleton-dependent dynamics of the human serotonin1A receptor
      correlates with receptor signaling.
AB  - Analyzing the dynamics of membrane proteins in the context of cellular signaling
      represents a challenging problem in contemporary cell biology. Lateral diffusion
      of lipids and proteins in the cell membrane is known to be influenced by the
      cytoskeleton. In this work, we explored the role of the actin cytoskeleton on the
      mobility of the serotonin(1A) (5-HT(1A)) receptor, stably expressed in CHO cells,
      and its implications in signaling. FRAP analysis of 5-HT(1A)R-EYFP shows that
      destabilization of the actin cytoskeleton induced by either CD or elevation of
      cAMP levels mediated by forskolin results in an increase in the mobile fraction
      of the receptor. The increase in the mobile fraction is accompanied by a
      corresponding increase in the signaling efficiency of the receptor.
      Interestingly, with increasing concentrations of CD used, the increase in the
      mobile fraction exhibited a correlation of approximately 0.95 with the efficiency
      in ligand-mediated signaling of the receptor. Radioligand binding and G-protein
      coupling of the receptor were found to be unaffected upon treatment with CD. Our
      results suggest that signaling by the serotonin(1A) receptor is correlated with
      receptor mobility, implying thereby that the actin cytoskeleton could play a
      regulatory role in receptor signaling. These results may have potential
      significance in the context of signaling by GPCRs in general and in the
      understanding of GPCR-cytoskeleton interactions with respect to receptor
      signaling in particular.

PMID- 18339760
TI  - Low-frequency stimulation induces stable transitions in stereotypical activity in
      cortical networks.
AB  - Reverberating spontaneous synchronized brain activity is believed to play an
      important role in neural information processing. Whether and how external stimuli
      can influence this spontaneous activity is poorly understood. Because periodic
      synchronized network activity is also prominent in in vitro neuronal cultures, we
      used cortical cultures grown on multielectrode arrays to examine how spontaneous
      activity is affected by external stimuli. Spontaneous network activity before and
      after low-frequency electrical stimulation was quantified in several ways. Our
      results show that the initially stable pattern of stereotypical spontaneous
      activity was transformed into another activity pattern that remained stable for
      at least 1 h. The transformations consisted of changes in single site and culture
      wide network activity as well as in the spatiotemporal dynamics of network
      bursting. We show for the first time that low-frequency electrical stimulation
      can induce long-lasting alterations in spontaneous activity of cortical neuronal
      networks. We discuss whether the observed transformations in network activity
      could represent a switch in attractor state.

PMID- 18339761
TI  - Quantification of electroporative uptake kinetics and electric field
      heterogeneity effects in cells.
AB  - We have conducted experiments quantitatively investigating electroporative uptake
      kinetics of a fluorescent plasma membrane integrity indicator, propidium iodide
      (PI), in HL60 human leukemia cells resulting from exposure to 40 mus pulsed
      electric fields (PEFs). These experiments were possible through the use of
      calibrated, real-time fluorescence microscopy and the development of a
      microcuvette: a specialized device designed for exposing cell cultures to intense
      PEFs while carrying out real-time microscopy. A finite-element electrostatic
      simulation was carried out to assess the degree of electric field heterogeneity
      between the microcuvette's electrodes allowing us to correlate trends in
      electroporative response to electric field distribution. Analysis of experimental
      data identified two distinctive electroporative uptake signatures: one
      characterized by low-level, decelerating uptake beginning immediately after PEF
      exposure and the other by high-level, accelerating fluorescence that is
      manifested sometimes hundreds of seconds after PEF exposure. The qualitative
      nature of these fluorescence signatures was used to isolate the conditions
      required to induce exclusively transient electroporation and to discuss
      electropore stability and persistence. A range of electric field strengths
      resulting in transient electroporation was identified for HL60s under our
      experimental conditions existing between 1.6 and 2 kV/cm. Quantitative analysis
      was used to determine that HL60s experiencing transient electroporation
      internalized between 50 and 125 million nucleic acid-bound PI molecules per cell.
      Finally, we show that electric field heterogeneity may be used to elicit
      asymmetric electroporative PI uptake within cell cultures and within individual
      cells.

PMID- 18339762
TI  - Folding myoglobin within a sol-gel glass: protein folding constrained to a small
      volume.
AB  - The unfolding and refolding reaction of myoglobin was examined in solution and
      within a porous silica sol-gel glass. The sol-gel pores constrain the protein to
      a volume that is the same size and shape as the folded native state accompanied
      by a few layers of water solvation. Denaturants such as low pH buffers can be
      diffused through the gel pores to the protein to initiate unfolding and
      refolding. Acid-induced unfolding was hindered by the steric constraints imposed
      by the gel pores such that more denaturing conditions were required within the
      gel than in solution to create the unfolded state. No new folding intermediates
      were observed. Refolding of myoglobin was not complete in millimolar pH 7 buffer
      alone. Addition of 25% glycerol to the pH 7 buffer resulted in nearly complete
      refolding, and the use of 1 M phosphate buffer resulted in complete refolding.
      The role of this cosolvent and salt in disrupting the ordered water surrounding
      the protein within the gel is discussed in light of the Hofmeister series and
      entropic trapping via a diminished hydrophobic effect within the gel. These
      results are consistent with the premises of folding models in which secondary and
      tertiary structures are considered to form within a compact conformation of the
      protein backbone.

PMID- 18339763
TI  - Total internal reflection fluorescence correlation spectroscopy: effects of
      lateral diffusion and surface-generated fluorescence.
AB  - Fluorescence correlation spectroscopy with total internal reflection excitation
      (TIR-FCS) is a promising method with emerging biological applications for
      measuring binding dynamics of fluorescent molecules to a planar substrate as well
      as diffusion coefficients and concentrations at the interface. Models for
      correlation functions proposed so far are rather approximate for most conditions,
      since they neglect lateral diffusion of fluorophores. Here we propose accurate
      extensions of previously published models for axial correlation functions taking
      into account lateral diffusion through detection profiles realized in typical
      experiments. In addition, we consider the effects of surface-generated emission
      in objective-based TIR-FCS. The expressions for correlation functions presented
      here will facilitate quantitative and accurate measurements with TIR-FCS.

PMID- 18339764
TI  - Structure and dynamics of the force-generating domain of myosin probed by
      multifrequency electron paramagnetic resonance.
AB  - Spin-labeling and multifrequency EPR spectroscopy were used to probe the dynamic
      local structure of skeletal myosin in the region of force generation. Subfragment
      1 (S1) of rabbit skeletal myosin was labeled with an iodoacetamide spin label at
      C707 (SH1). X- and W-band EPR spectra were recorded for the apo state and in the
      presence of ADP and nucleotide analogs. EPR spectra were analyzed in terms of
      spin-label rotational motion within myosin by fitting them with simulated
      spectra. Two models were considered: rapid-limit oscillation (spectrum-dependent
      on the orientational distribution only) and slow restricted motion (spectrum
      dependent on the rotational correlation time and the orientational distribution).
      The global analysis of spectra obtained at two microwave frequencies (9.4 GHz and
      94 GHz) produced clear support for the second model and enabled detailed
      determination of rates and amplitudes of rotational motion and resolution of
      multiple conformational states. The apo biochemical state is well-described by a
      single structural state of myosin (M) with very restricted slow motion of the
      spin label. The ADP-bound biochemical state of myosin also reveals a single
      structural state (M*, shown previously to be the same as the post-powerstroke ATP
      bound state), with less restricted slow motion of the spin label. In contrast,
      the extra resolution available at 94 GHz reveals that the EPR spectrum of the
      S1.ADP.V(i)-bound biochemical state of myosin, which presumably mimics the
      S1.ADP.P(i) state, is resolved clearly into three spectral components (structural
      states). One state is indistinguishable from that of the ADP-bound state (M*) and
      is characterized by moderate restriction and slow motion, with a mole fraction of
      16%. The remaining 84% (M**) contains two additional components and is
      characterized by fast rotation about the x axis of the spin label. After
      analyzing EPR spectra, myosin ATPase activity, and available structural
      information for myosin II, we conclude that post-powerstroke and pre-powerstroke
      structural states (M* and M**) coexist in the S1.ADP.V(i) biochemical state. We
      propose that the pre-powerstroke state M** is characterized by two structural
      states that could reflect flexibility between the converter and N-terminal
      domains of myosin.

PMID- 18339765
TI  - Early stages of amyloid fibril formation studied by liquid-state NMR: the peptide
      hormone glucagon.
AB  - The 29-residue peptide hormone glucagon forms amyloid fibrils within a few hours
      at low pH. In this study, we use glucagon as a model system to investigate fibril
      formation by liquid-state (1)H-NMR spectroscopy One-dimensional, correlation, and
      diffusion experiments monitoring the fibril formation process provide insight
      into the early stages of the pathway on which the molecules aggregate to fibrils.
      In conjunction with these techniques, exchange experiments give information about
      the end-state conformation. Within the limits of detection, there are no signs of
      larger oligomeric intermediates in the course of the fibril formation process.
      Kinetic information is extracted from the time course of the residual free
      glucagon signal decay. This suggests that glucagon amyloids form by a nucleated
      growth mechanism in which trimers (rather than monomers) of glucagon interact
      directly with the growing fibrils rather than with each other. The results of
      proton/deuterium exchange experiments on mature fibrils with subsequent
      dissolution show that the N-terminal of glucagon is the least amenable to
      exchange, which indicates that this part is strongly involved in the
      intermolecular bonds of the fibrils.

PMID- 18339766
TI  - On the signaling mechanism and the absence of photoreversibility in the AppA BLUF
      domain.
AB  - The flavoprotein AppA from Rhodobacter sphaeroides contains an N-terminal, FAD
      binding BLUF photoreceptor domain. Upon illumination, the AppA BLUF domain forms
      a signaling state that is characterized by red-shifted absorbance by 10 nm, a
      state known as AppA(RED). We have applied ultrafast spectroscopy on the
      photoaccumulated AppA(RED) state to investigate the photoreversible properties of
      the AppA BLUF domain. On light absorption by AppA(RED), the FAD singlet excited
      state FAD(RED)* decays monoexponentially in 7 ps to form the neutral semiquinone
      radical FADH(*), which subsequently decays to the original AppA(RED) molecular
      ground state in 60 ps. Thus, FAD(RED)* is deactivated rapidly via electron and
      proton transfer, probably from the conserved tyrosine Tyr-21 to FAD, followed by
      radical-pair recombination. We conclude that, in contrast to many other
      photoreceptors, the AppA BLUF domain is not photoreversible and does not enter
      alternative reaction pathways upon absorption of a second photon. To explain
      these properties, we propose that a molecular configuration is formed upon
      excitation of AppA(RED) that corresponds to a forward reaction intermediate
      previously identified for the dark-state BLUF photoreaction. Upon excitation of
      AppA(RED), the BLUF domain therefore enters its forward reaction coordinate,
      readily re-forming the AppA(RED) ground state and suppressing reverse or side
      reactions. The monoexponential decay of FAD* indicates that the FAD-binding
      pocket in AppA(RED) is significantly more rigid than in dark-state AppA. Steady
      state fluorescence experiments on wild-type, W104F, and W64F mutant BLUF domains
      show tryptophan fluorescence maxima that correspond with a buried conformation of
      Trp-104 in dark and light states. We conclude that Trp-104 does not become
      exposed to solvent during the BLUF photocycle.

PMID- 18339767
TI  - Nonlinear relationship between level of blood flow and skin temperature for
      different dynamics of temperature change.
AB  - We present a study of the relationship between blood flow and skin temperature
      under different dynamics of skin-temperature-change: locally induced thermal
      shock and well controlled, gradual change. First, we demonstrate memory phenomena
      for blood flow and skin temperature under both conditions. Secondly, we point out
      that the "hysteresis" loops obtained are dependent on initial conditions,
      indicating physiological response times of more than twenty minutes. We also show
      that under thermal shock the level of blood flow is preserved up to some
      characteristic temperature limit, independently of subject.

PMID- 18339768
TI  - Neural stem cell targeting of glioma is dependent on phosphoinositide 3-kinase
      signaling.
AB  - The utility of neural stem cells (NSCs) has extended beyond regenerative medicine
      to targeted gene delivery, as NSCs possess an inherent tropism to solid tumors,
      including invasive gliomas. However, for optimal clinical implementation, an
      understanding of the molecular events that regulate NSC tumor tropism is needed
      to ensure their safety and to maximize therapeutic efficacy. We show that human
      NSC lines responded to multiple tumor-derived growth factors and that hepatocyte
      growth factor (HGF) induced the strongest chemotactic response. Gliomatropism was
      critically dependent on c-Met signaling, as short hairpin RNA-mediated ablation
      of c-Met significantly attenuated the response. Furthermore, inhibition of Ras
      phosphoinositide 3-kinase (PI3K) signaling impaired the migration of human neural
      stem cells (hNSCs) toward HGF and other growth factors. Migration toward tumor
      cells is a highly regulated process, in which multiple growth factor signals
      converge on Ras-PI3K, causing direct modification of the cytoskeleton. The
      signaling pathways that regulate hNSC migration are similar to those that promote
      unregulated glioma invasion, suggesting shared cellular mechanisms and responses.
      Disclosure of potential conflicts of interest is found at the end of this
      article.

PMID- 18339769
TI  - Fibroblast growth factor 2 maintains the neurogenic capacity of embryonic neural
      progenitor cells in vitro but changes their neuronal subtype specification.
AB  - Many in vitro systems used to examine multipotential neural progenitor cells
      (NPCs) rely on mitogens including fibroblast growth factor 2 (FGF2) for their
      continued expansion. However, FGF2 has also been shown to alter the expression of
      transcription factors (TFs) that determine cell fate. Here, we report that NPCs
      from the embryonic telencephalon grown without FGF2 retain many of their in vivo
      characteristics, making them a good model for investigating molecular mechanisms
      involved in cell fate specification and differentiation. However, exposure of
      cortical NPCs to FGF2 results in a profound change in the types of neurons
      generated, switching them from a glutamatergic to a GABAergic phenotype. This
      change closely correlates with the dramatic upregulation of TFs more
      characteristic of ventral telencephalic NPCs. In addition, exposure of cortical
      NPCs to FGF2 maintains their neurogenic potential in vitro, and NPCs
      spontaneously undergo differentiation following FGF2 withdrawal. These results
      highlight the importance of TFs in determining the types of neurons generated by
      NPCs in vitro. In addition, they show that FGF2, as well as acting as a mitogen,
      changes the developmental capabilities of NPCs. These findings have implications
      for the cell fate specification of in vitro-expanded NPCs and their ability to
      generate specific cell types for therapeutic applications. Disclosure of
      potential conflicts of interest is found at the end of this article.

PMID- 18339770
TI  - Bone marrow-derived stem cells do not reconstitute spermatogenesis in vivo.

PMID- 18339771
TI  - Mobilization of hematopoietic progenitor cells by yeast-derived beta-glucan
      requires activation of matrix metalloproteinase-9.
AB  - Poly-(1,6)-beta-d-glucopyranosyl-(1,3)-beta-d-glucopyranose (PGG) beta-glucan is
      a soluble yeast-derived polysaccharide that has previously been shown to induce
      hematopoietic progenitor cell (HPC) mobilization. However, the mobilizing
      mechanism of action remains unknown. Here, we confirmed that PGG beta-glucan
      alone or in combination with granulocyte colony-stimulating factor (G-CSF)
      mobilizes HPC into the periphery. Optimal mobilizing effects were seen 24-48
      hours after PGG beta-glucan doses of 4.8-9.6 mg/kg. Animals treated with G-CSF
      and PGG beta-glucan showed a collaborative effect in HPC mobilization compared
      with G-CSF treatment alone. Additional studies demonstrated that neither
      complement 3 nor complement receptor 3 played a role in this effect and that PGG
      beta-glucan treatment did not induce proinflammatory cytokine secretion. However,
      bone marrow cells from PGG beta-glucan-treated mice secreted abundant matrix
      metalloproteinase-9 (MMP-9), and PGG beta-glucan-induced HPC mobilization was
      abrogated in MMP-9 knockout mice. Moreover, we demonstrated that both
      hematopoietic and nonhematopoietic cells contributed to MMP-9 secretion upon PGG
      beta-glucan treatment. In addition, HPCs mobilized by PGG beta-glucan had similar
      levels of engraftment in host and lineage differentiation capability compared
      with those mobilized by G-CSF. Thus, PGG beta-glucan is an agent that enhances
      HPC mobilization and may improve the outcome of clinical stem cell
      transplantation.

PMID- 18339772
TI  - Embryonic porcine liver as a source for transplantation: advantage of intact
      liver implants over isolated hepatoblasts in overcoming homeostatic inhibition by
      the quiescent host liver.
AB  - Cell therapy as an alternative to orthotopic liver transplantation represents a
      major challenge, since negligible proliferation of isolated hepatocytes occurs
      after transplantation because of the stringent homeostatic control displayed by
      the host liver. Thus, different modalities of liver injury as part of the
      pretransplant conditioning are a prerequisite for this approach. The major
      objective of the present study was to test whether xenotransplantation of pig
      fetal liver fragments, in which potential cell-cell and cell-stroma interactions
      are spared, might afford more robust growth and proliferation compared with
      isolated pig fetal hepatoblasts. After transplantation into SCID mice, fetal
      liver tissue fragments exhibited marked growth and proliferation, in the setting
      of a quiescent host liver, compared with isolated fetal hepatoblasts harvested at
      the same gestational age (embryonic day 28). The proliferative advantage of fetal
      pig liver fragments was clearly demonstrated by immunohistochemical and
      morphometric assays and was observed not only after implantation into the liver
      but also into extrahepatic sites, such as the spleen and the subrenal capsule.
      The presence of all types of nonparenchymal liver cells that is crucial for
      normal liver development and regeneration was demonstrated in the implants.
      Preservation of the three-dimensional structure in pig fetal liver fragments
      enables autonomous proliferation of transplanted hepatic cells in the setting of
      a quiescent host liver, without any requirement for liver injury in the
      pretransplant conditioning. The marked proliferation and functional maturation
      exhibited by the pig fetal liver fragments suggests that it could afford a
      preferable source for transplantation.

PMID- 18339773
TI  - Sohlh2 knockout mice are male-sterile because of degeneration of differentiating
      type A spermatogonia.
AB  - The spermatogenesis and oogenesis-specific transcription factor Sohlh2 is
      normally expressed only in premeiotic germ cells. In this study, Sohlh2 and
      several other germ cell transcripts were found to be induced in mouse embryonic
      stem cells when cultured on a feeder cell line that overexpresses bone
      morphogenetic protein 4. To study the function of Sohlh2 in germ cells, we
      generated mice harboring null alleles of Sohlh2. Male Sohlh2-deficient mice were
      infertile because of a block in spermatogenesis. Although normal prior to birth,
      Sohlh2-null mice had reduced numbers of intermediate and type B spermatogonia by
      postnatal day 7. By day 10, development to the preleptotene spermatocyte stage
      was severely disrupted, rendering seminiferous tubules with only Sertoli cells,
      undifferentiated spermatogonia, and degenerating colonies of differentiating
      spermatogonia. Degenerating cells resembled type A2 spermatogonia and accumulated
      in M-phase prior to death. A similar phenotype was observed in Sohlh2-null mice
      on postnatal days 14, 21, 35, 49, 68, and 151. In adult Sohlh2-mutant mice, the
      ratio of undifferentiated type A spermatogonia (DAZL+/PLZF+) to differentiating
      type A spermatogonia (DAZL+/PLZF-) was twice normal levels. In culture,
      undifferentiated type A spermatogonia isolated from Sohlh2-null mice proliferated
      normally but linked the mutant phenotype to aberrant cell surface expression of
      the receptor-tyrosine kinase cKit. Thus, Sohlh2 is required for progression of
      differentiating type A spermatogonia into type B spermatogonia. One conclusion
      originating from these studies would be that testicular factors normally regulate
      the viability of differentiating spermatogonia by signaling through Sohlh2. This
      regulation would provide a crucial checkpoint to optimize the numbers of
      spermatocytes entering meiosis during each cycle of spermatogenesis. Disclosure
      of potential conflicts of interest is found at the end of this article.

PMID- 18339774
TI  - Dysphagia dietary guidelines and the rheology of nutritional feeds and barium
      test feeds.
AB  - BACKGROUND: Dysphagia can lead to aspiration of oral feeds, thus causing
      pneumonia. Dysphagia is diagnosed by assessing the ability to swallow barium test
      feeds (BTF) of different viscosities. Dysphagia diet foods (DDF) are thickened as
      recommended by the National Dysphagia Diet (NDD) guidelines. To our knowledge,
      there are no published data evaluating if the viscosity of BTF or commercial DDF
      meet NDD guidelines. METHODS: A TA1000 rheometer (TA Instruments; New Castle, DE)
      measured dynamic viscosity of BTF and DDF using creep transformation under
      controlled stress. Thin DDF studied included Plus Energy Drink (Boost;
      Novartis/Nestle; Fremont, MI) and Instant Breakfast (Carnation; Wilkes-Barre, PA)
      and nectar- and honey-thick DDF from Hormel (Hormel Health Labs; Savannah, GA)
      and Novartis (Novartis/Nestle). The BTF studied were thin, nectar-, and honey
      thick Polibar barium suspension or Varibar (E-Z-EM, Inc.; Lake Success, NY). We
      measured batch-to-batch variability in the viscosity of DDF, with and without
      shaking, and after 2 h at ambient temperature at a shear rate chosen to match
      natural swallowing. RESULTS: We observed the following: (1) DDF: the viscosity of
      honey-thick DDF was consistent with NDD guidelines, but other products were not.
      All products had minimal change in viscosity over 2 h. Boost thin liquid had >
      300% increase in viscosity after shaking. (2) BTF: thin barium had a viscosity
      consistent with NDD guidelines. The nectar- and honey-thick Polibar BTFs were
      thixotropic and had unacceptably high viscosity. Varibar BTFs were not
      thixotropic but were more viscous than the NDD guidelines. CONCLUSIONS: There was
      a poor relationship between the viscosity of DDF and BTF. The viscosity of BFTs
      is much greater than the correspondingly named diet foods and the NDD guidelines.
      This can place patients at significant risk for oral aspiration.

PMID- 18339775
TI  - Role of surgical lung biopsy in separating chronic hypersensitivity pneumonia
      from usual interstitial pneumonia/idiopathic pulmonary fibrosis: analysis of 31
      biopsies from 15 patients.
AB  - BACKGROUND: Lung biopsy has been proposed as a criterion for diagnosis of chronic
      hypersensitivity pneumonia (HP), especially in patients without proven antigen
      exposure. Histologic findings in some suspected HP patients overlap with usual
      interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). We
      reviewed our experience to determine the specificity of histologic findings in
      surgical lung biopsies from patients with clinical diagnoses of HP. METHODS:
      Surgical lung biopsies from patients with chronic HP, idiopathic pulmonary
      fibrosis, and idiopathic NSIP were reviewed retrospectively without knowledge of
      the clinical diagnosis. Each specimen was assigned a histologic diagnosis, and
      selected histologic findings were tabulated. Clinical data were abstracted from
      medical records. RESULTS: Fifteen patients with clinical diagnoses of chronic HP
      underwent biopsy of one to three lobes. Ten showed features diagnostic of HP in
      all specimens. Two had discordant findings that included HP in one specimen and
      UIP or nonspecific changes in others. Biopsies from two showed only UIP, and one
      showed NSIP. Diagnostic features were present in all samples from 9 of the 11
      patients with more than one biopsy site (81.8%). Three patients died of disease,
      including both patients from whom biopsies showed only UIP. CONCLUSIONS: Most
      patients with a clinical diagnosis of chronic HP have supportive histologic
      findings in surgical lung biopsies. A subset of HP patients has findings
      indistinguishable from UIP. Sampling from more than one lobe may be helpful in
      separating HP from idiopathic pulmonary fibrosis.

PMID- 18339776
TI  - Sleep-related breathing disorders in patients with pulmonary hypertension.
AB  - BACKGROUND: Cheyne-Stokes respiration (CSR) and central sleep apnea (CSA) are
      common in patients with left-heart failure. We investigated the hypothesis that
      sleep-disordered breathing is also prevalent in patients with right ventricular
      dysfunction due to pulmonary hypertension (PH). METHODS: We studied 38
      outpatients (median age, 61 years; quartiles, 51 to 72) with pulmonary arterial
      hypertension (n = 23) or chronic thromboembolic PH (n = 15). New York Heart
      Association (NYHA) class was II to IV, and median 6-min walk distance was 481 m
      (quartiles, 429 to 550). In-laboratory polysomnography (n = 22) and ambulatory
      cardiorespiratory sleep studies (n = 38) including pulse oximetry were performed.
      Quality of life and sleepiness by the Epworth sleepiness score were assessed.
      RESULTS: The median apnea/hypopnea index was 8 events/h (quartiles, 4 to 19),
      with 8 central events (quartiles, 4 to 17), and 0 obstructive events (quartiles,
      0 to 0.3) per hour. Seventeen patients (45%) had > or = 10 apnea/hypopnea
      events/h. Comparison of 13 patients with > or = 10 CSR/CSA events/h with 21
      patients with < 10 CSR/CSA events/h (excluding 4 patients with > or = 10
      obstructive events/h from this analysis) revealed no difference in regard to
      hemodynamics, NYHA class, and Epworth sleepiness scores. However, patients with >
      or = 10 CSR/CSA events/h had a reduced quality of life in the physical domains.
      Ambulatory cardiorespiratory sleep studies accurately predicted > or = 10
      apnea/hypopnea events/h during polysomnography in patients who underwent both
      studies (area under the receiver operating characteristic curve, 0.93; SE +/-
      0.06; p = 0.002). The corresponding value for pulse oximetry was 0.63 +/- 0.14 (p
      = not significant). CONCLUSIONS: In patients with PH, CSR/CSA is common, but
      obstructive sleep apnea also occurs. Sleep-related breathing disorders are not
      associated with excessive sleepiness but affect quality of life. They should be
      evaluated by polysomnography or cardiorespiratory sleep studies because pulse
      oximetry may fail to detect significant sleep apnea.

PMID- 18339777
TI  - Generation of oxidants by hypoxic human pulmonary and coronary smooth-muscle
      cells.
AB  - BACKGROUND: Pulmonary vasoconstriction in response to hypoxia is unusual inasmuch
      as local exposure of nonpulmonary vasculature to hypoxia results in vasodilation.
      It has been suggested that pulmonary artery smooth-muscle cells may relax in
      response to intracellular generation of reactive oxygen species (ROS) and that
      the production of ROS decreases under hypoxia. However, other workers report
      increased ROS production in human pulmonary artery smooth-muscle cells (HPASMC)
      during hypoxia. METHODS: Using dihydrodichlorofluorescein diacetate,
      dihydroethidium, and Amplex Red (Molecular Probes; Eugene, OR), we estimated ROS
      generation by confluent primary cultures of HPASMC and human coronary artery
      smooth-muscle cells (HCASMC) under normoxia (20%) and acute hypoxia (5%).
      RESULTS: All three assay systems showed that HPASMC production of ROS is
      decreased under hypoxia and to a greater extent than the decrease in ROS
      production by HCASMC. A substantially greater percentage of normoxic ROS
      production by HPASMC is mitochondrial (> 60%) compared to HCASMC (< 30%).
      CONCLUSIONS: These results support the conclusion that ROS generation decreases,
      rather than increases, in HPASMC during hypoxia. However, as ROS production also
      decreases in HCASMC during hypoxia, the reason for the opposite change in
      vascular tone is not yet apparent.

PMID- 18339778
TI  - Restoration of cough reflex in lung transplant recipients.
AB  - BACKGROUND: Lung transplantation involves vagal nerve interruption resulting in
      sensory airway denervation and impairment of the cough reflex. Following lung
      transplantation, it is unclear whether functional recovery of the cough reflex
      occurs over time. Our objective was to evaluate the afferent limb of the cough
      reflex in lung transplant recipients. METHODS: The assessment of cough reflex
      involved upper airway anesthesia, conscious sedation, and fiberoptic
      bronchoscopy; the biopsy forceps and a 5% dextrose solution were applied through
      the bronchoscope to the airway mucosa at the main carina, proximal and distal to
      the anastomosis. A cross-sectional group of seven subjects underwent a single
      assessment, while eight subjects in a longitudinal group underwent assessment at
      1.5 and 12 months. Cough frequency was determined by counting the number of
      audible coughs and abdominal muscle contractions measured with a surface
      electromyogram recorder. The airway anastomosis from deceased subjects in the
      longitudinal group was examined for nerves. RESULTS: All seven subjects from the
      cross-sectional group demonstrated a similar cough frequency after mechanical and
      chemical irritation of all airway sites. All subjects in the longitudinal group
      who were evaluated at 1.5 weeks had a cough response at all sites except distal
      to the anastomosis. Twelve months after transplantation, cough was present at all
      sites. Immunohistochemical staining for protein gene product 9.5, low-affinity
      neurotrophin, and vanilloid receptors demonstrated nerves in subepithelial
      regions proximal and distal to the airway anastomosis. CONCLUSION: In human lung
      transplant recipients, recovery of the cough reflex was noted 12 months after
      lung transplantation.

PMID- 18339779
TI  - Blood glucose control in critically ill adults and children: a survey on stated
      practice.
AB  - OBJECTIVES: We document clinicians' stated blood glucose control practice
      patterns in North American pediatric and adult ICUs. METHODS: Using a Web-based
      self-administered questionnaire, we conducted a nationwide survey of North
      American pediatric and adult ICUs. Participants included ICU medical directors,
      nurses, fellows in training, and attending intensivists from participating ICUs
      in three critical care research networks. MEASUREMENTS AND MAIN RESULTS: Item
      generation and item selection were performed according to standard scientific
      survey methods. Questions were designed to describe clinicians' perceptions about
      glucose control practices. The questionnaire topics included the following:
      respondent characteristics; ICU description; hyperglycemia; hypoglycemia; and
      glucose measurement. The institutional response rate was 96% (50 of 52
      institutions). The clinician response rate was 58% (163 of 282 physicians). Adult
      ICU clinicians defined hyperglycemia (120 mg/dL [6.2 mmol/L]) at a lower
      threshold than pediatric ICU clinicians (150 mg/dL [8.3 mmol/L]). Hypoglycemia
      was defined similarly by both groups (median, < or = 60 mg/dL [3.3 mmol/L];
      range, 40 to 80 mg/dL [2.2 to 4.4 mmol/L]). More pediatric ICU clinicians (84.5%)
      than adult ICU clinicians (59.1%) considered hypoglycemia to be more dangerous
      than hyperglycemia. A larger percentage of adult ICU clinicians (82.5%) than
      pediatric ICU clinicians (49.3%) preferred a target blood glucose level between
      80 and 110 mg/dL (4.4 to 6.1 mmol/L). Clinical algorithms for glucose management
      varied among clinicians and across institutions. CONCLUSIONS: Blood glucose
      control with insulin is used frequently for critically ill adults and children. A
      wide variation in practice exists in blood glucose targets, hyperglycemia and
      hypoglycemia definitions, and decision algorithms among North American adult and
      pediatric ICUs.

PMID- 18339780
TI  - Left ventricular diastolic dysfunction in patients with COPD in the presence and
      absence of elevated pulmonary arterial pressure.
AB  - BACKGROUND: Increased right ventricular afterload leads to left ventricular
      diastolic dysfunction due to ventricular interdependence. Increased right
      ventricular afterload is frequently present in patients with COPD. The purpose of
      this study was to determine whether left ventricular diastolic dysfunction could
      be detected in COPD patients with normal or elevated pulmonary artery pressure
      (PAP). METHODS: Twenty-two patients with COPD and 22 matched control subjects
      underwent pulsed Doppler echocardiography. Left ventricular systolic dysfunction
      and other causes of left ventricular diastolic dysfunction (eg, coronary artery
      disease) were excluded in all patients and control subjects. PAP was measured
      invasively in 13 patients with COPD. RESULTS: The maximal atrial filling velocity
      was increased and the early filling velocity was decreased in patients with COPD
      compared to control subjects. The early flow velocity peak/late flow velocity
      peak (E/A) ratio was markedly decreased in patients with COPD compared to control
      subjects (0.79 +/- 0.035 vs 1.38 +/- 0.069, respectively; p < 0.0001), indicating
      the presence of left ventricular diastolic dysfunction. The atrial contribution
      to total left diastolic filling was increased in patients with COPD. This was
      also observed in COPD patients with normal PAP, as ascertained using a right
      heart catheter. The atrial contribution to total left diastolic filling was
      further increased in COPD patients with PAP. PAP correlated with the E/A ratio (r
      = -0.85; p < 0.0001). CONCLUSIONS: Left ventricular diastolic dysfunction is
      present in COPD patients with normal PAP and increases with right ventricular
      afterload.

PMID- 18339781
TI  - Pulmonary nodular ground-glass opacities in patients with extrapulmonary cancers:
      what is their clinical significance and how can we determine whether they are
      malignant or benign lesions?
AB  - BACKGROUND: The clinical significance of pulmonary nodular ground-glass opacities
      (NGGOs) in patients with extrapulmonary cancers is not known, although there is
      an urgent need for study on this topic. The purpose of this study, therefore, was
      to investigate the clinical significance of pulmonary NGGOs in these patients,
      and to develop a computerized scheme to distinguish malignant from benign NGGOs.
      METHODS: Fifty-nine pathologically proven pulmonary NGGOs in 34 patients with a
      history of extrapulmonary cancer were studied. We reviewed the CT scan
      characteristics of NGGOs and the clinical features of these patients. Artificial
      neural networks (ANNs) were constructed and tested as a classifier distinguishing
      malignant from benign NGGOs. The performance of ANNs was evaluated with receiver
      operating characteristic analysis. RESULTS: Twenty-eight patients (82.4%) were
      determined to have malignancies. Forty NGGOs (67.8%) were diagnosed as
      malignancies (adenocarcinomas, 24; bronchioloalveolar carcinomas, 16). Among the
      rest of the NGGOs, 14 were atypical adenomatous hyperplasias, 4 were focal
      fibrosis, and 1 was an inflammatory nodule. There were no cases of metastasis
      appearing as NGGOs. Between malignant and benign NGGOs, there were significant
      differences in lesion size; the presence of internal solid portion; the size and
      proportion of the internal solid portion; the lesion margin; and the presence of
      bubble lucency, air bronchogram, or pleural retraction (p < 0.05). Using these
      characteristics, ANNs showed excellent accuracy (z value, 0.973) in
      discriminating malignant from benign NGGOs. CONCLUSIONS: Pulmonary NGGOs in
      patients with extrapulmonary cancers tend to have high malignancy rates and are
      very often primary lung cancers. ANNs might be a useful tool in distinguishing
      malignant from benign NGGOs.

PMID- 18339782
TI  - Variability in small airway epithelial gene expression among normal smokers.
AB  - BACKGROUND: Despite overwhelming data that cigarette smoking causes COPD, only a
      minority of long-term smokers are affected, strongly suggesting that genetic
      factors modify susceptibility to this disease. We hypothesized that individual
      variations exist in the response to cigarette smoking, with variability among
      smokers in expression levels of protective/susceptibility genes. METHODS:
      Affymetrix arrays and quantitative polymerase chain reaction were used to assess
      the variability of gene expression in the small airway epithelium obtained by
      fiberoptic bronchoscopy of 18 normal nonsmokers, 18 normal smokers, and 18
      smokers with COPD. RESULTS: We identified 201 probe sets representing 152 smoking
      responsive genes that were significantly up-regulated or down-regulated, and
      assessed the coefficient of variation in expression levels among the study
      population. Variation was a reproducible property of each gene as assessed by
      different microarray probe sets and real-time polymerase chain reaction, and was
      observed in both normal smokers and smokers with COPD. Greater individual
      variability was found in smokers with COPD than in normal smokers. The majority
      of these highly variable smoking-responsive genes were in the functional
      categories of signal transduction, xenobiotic degradation, metabolism, transport,
      oxidant related, and transcription. A similar pattern of the same highly variable
      genes was observed in an independent data set. CONCLUSIONS: We propose that
      genetic diversity is likely within this subset of genes, with highly variable
      individual-to-individual responses of the small airway epithelium to smoking, and
      that this subset of genes represents putative candidates for assessment of
      susceptibility/protection from disease in future gene-based epidemiologic studies
      of smokers' risk for COPD.

PMID- 18339783
TI  - Combined oximetry-cutaneous capnography in patients assessed for long-term oxygen
      therapy.
AB  - STUDY AIM: To evaluate the feasibility of combined oximetry (pulse oximetric
      saturation [Spo(2)]) and cutaneous capnography (transcutaneous carbon dioxide
      tension [Ptcco(2)]) for oxygen titration in patients requiring long-term oxygen
      therapy. METHODS: Twenty patients with obstructive or restrictive lung disease
      underwent oxygen titration using a combined cutaneous oximetry-capnography
      sensor. The goal of titration was to achieve an oxygen saturation of > 90%
      without a significant rise in carbon dioxide. Spo(2) and Ptcco(2) measurements at
      the end of titration were compared with blood gas levels using Bland-Altman
      analysis and linear regression analysis. RESULTS: The mean (+/- SE of the
      estimate) Pao(2) while breathing room air was 53.2 +/- 8.1 mm Hg and increased to
      75.9 +/- 13.3 mm Hg with oxygen supplementation (p < 0.0001). The mean Paco(2)
      was 45.9 +/- 8.7 mm Hg at baseline and 47.8 +/- 9.0 mm Hg after oxygen titration
      (p = 0.003). Bland-Altman analysis for comparison of Ptcco(2) and Paco(2) showed
      a bias of 0.86 mm Hg with a precision of 3.48 mm Hg. Bland-Altman analysis for
      the comparison of Spo(2) and arterial oxygen saturation showed a bias of 0.14%
      with a precision of 1.13%. CONCLUSION: Combined oximetry and cutaneous
      capnography is feasible during oxygen titration in patients needing long-term
      oxygen therapy. This noninvasive approach has the potential to reduce the number
      of arterial blood gas samplings performed.

PMID- 18339784
TI  - Cardiac involvement in patients with sarcoidosis: diagnostic and prognostic value
      of outpatient testing.
AB  - BACKGROUND: Cardiac sarcoidosis (CS) causes substantial morbidity and sudden
      death. Early diagnosis and risk stratification are warranted. METHODS: Ambulatory
      patients with sarcoidosis were interviewed to determine whether they experienced
      palpitations, syncope, or presyncope, and were evaluated with ECG, Holter
      monitoring, and echocardiography (transthoracic echocardiogram [TTE]). Those with
      symptoms or abnormal results were studied with cardiac MRI (CMRI) or positron
      emission tomography (PET) scanning. The diagnosis of CS was based on
      abnormalities detected by these imaging studies. Patients with CS were referred
      for risk stratification by electrophysiology study (EPS). RESULTS: Among the 62
      patients evaluated, the prevalence of CS was 39%. Patients with CS had more
      cardiac symptoms than those without CS (46% vs 5%, respectively; p < 0.001), and
      were more likely to have abnormal Holter monitoring findings (50% vs 3%,
      respectively; p < 0.001) and TTE findings (25% vs 5%, respectively; p = 0.02).
      The degree of pulmonary impairment did not predict CS. Two of the 17 patients who
      underwent EPS had abnormal test findings and received implantable cardioverter
      defibrillators. No patients died, had ventricular arrhythmias that triggered
      defibrillator therapy, or had heart failure develop during almost 2 years of
      follow-up. This diagnostic approach was more sensitive than the established
      criteria for identifying CS. CONCLUSION: CS is common among patients with
      sarcoidosis. A structured clinical assessment incorporating advanced cardiac
      imaging with PET scanning or CMRI is more sensitive than the established criteria
      for the identification of CS. Sarcoidal lesions seen on CMRI or PET scanning do
      not predict arrhythmias in ambulatory patients with preserved cardiac function,
      who appear to be at low risk for short-term mortality.

PMID- 18339785
TI  - Influence of atrial fibrillation on plasma von willebrand factor, soluble E
      selectin, and N-terminal pro B-type natriuretic peptide levels in systolic heart
      failure.
AB  - BACKGROUND: Endothelial dysfunction is present in patients with heart failure
      (HF) due to left ventricular systolic dysfunction, as well as in patients with
      atrial fibrillation (AF) who have normal cardiac function. It is unknown whether
      AF influences the degree of endothelial dysfunction in patients with systolic HF.
      METHODS: We measured levels of plasma von Willebrand factor (vWF) and E-selectin
      (as indexes of endothelial damage/dysfunction and endothelial activation,
      respectively; both enzyme-linked immunosorbent assay) in patients with AF and HF
      (AF-HF), who were compared to patients with sinus rhythm and HF (SR-HF), as well
      as in age-matched, healthy, control subjects. We also assessed the relationship
      of vWF and E-selectin to plasma N-terminal pro B-type natriuretic peptide (NTpro
      BNP), a marker for HF severity and prognosis. RESULTS: One hundred ninety
      patients (73% men; mean age, 69.0 +/- 10.1 years [+/- SD]) with systolic HF were
      studied, who were compared to 117 healthy control subjects: 52 subjects (27%)
      were in AF, while 138 subjects (73%) were in sinus rhythm. AF-HF patients were
      older than SR-HF patients (p = 0.046), but left ventricular ejection fraction and
      New York Heart Association class were similar. There were significant differences
      in NT-proBNP (p < 0.0001) and plasma vWF (p = 0.003) between patients and control
      subjects. On Tukey post hoc analysis, AF-HF patients had significantly increased
      NT-proBNP (p < 0.001) and vWF (p = 0.0183) but not E-selectin (p = 0.071) levels
      when compared to SR-HF patients. On multivariate analysis, the presence of AF was
      related to plasma vWF levels (p = 0.018). Plasma vWF was also significantly
      correlated with NT-proBNP levels (Spearman r = 0.139; p = 0.017). CONCLUSIONS:
      There is evidence of greater endothelial damage/dysfunction in AF-HF patients
      when compared to SR-HF patients. The clinical significance of this is unclear but
      may have prognostic value.

PMID- 18339786
TI  - Impact of COPD on outcome among patients with complicated peptic ulcer.
AB  - BACKGROUND: COPD is associated with an increased risk of peptic ulcer disease,
      but limited data exist on whether COPD influences short-term mortality among
      patients with bleeding and a perforated peptic ulcer. We examined the association
      between COPD and 30-day mortality following bleeding and perforation of a peptic
      ulcer. METHODS: We identified all patients who had been hospitalized with a first
      time diagnosis of peptic ulcer perforation (n = 2,033) or bleeding (n = 7,486) in
      northern Denmark between 1991 and 2004. Information on COPD, comorbidities, and
      filled prescriptions was obtained from medical databases. Mortality was
      ascertained using the Danish Civil Registration System. We computed the
      cumulative 30-day mortality rates for ulcer patients with COPD and for other
      ulcer patients, and used regression analysis to obtain the 30-day mortality rate
      ratios (MRRs), controlling for potential confounding factors. RESULTS: Among
      patients who were hospitalized with perforated peptic ulcers, 218 (10.7%) had
      previously been hospitalized with COPD. The 30-day mortality rate was 44.0% among
      perforated ulcer patients with COPD vs 25.5% among other ulcer patients (adjusted
      MRR, 1.48; 95% confidence interval [CI], 1.18 to 1.85). Among patients
      hospitalized with a bleeding peptic ulcer, 759 (10.1%) had previously been
      hospitalized with COPD. The 30-day mortality rate was 16.5% among bleeding peptic
      ulcer patients with COPD vs 10.8% among other ulcer patients (adjusted MRR, 1.38;
      95% CI, 1.14 to 1.68). The use of oral glucocorticoids among COPD patients was
      associated with higher MRRs for both perforated and bleeding peptic ulcers.
      CONCLUSIONS: COPD substantially increased 30-day mortality among patients with
      bleeding and perforated peptic ulcers.

PMID- 18339787
TI  - C-reactive protein levels and survival in patients with moderate to very severe
      COPD.
AB  - BACKGROUND: Serum levels of C-reactive protein (CRP) are increased in patients
      with COPD and correlate modestly with variables predictive of outcomes. In
      epidemiologic studies, CRP level is associated with all-cause mortality in
      patients with mild-to-moderate disease. OBJECTIVE: To determine if CRP levels are
      associated with survival in patients with moderate to very severe COPD in
      comparison with other well-known prognostic parameters of the disease. METHODS:
      In 218 stable patients with COPD, we measured baseline serum CRP level, BODE
      (body mass index, obstruction, dyspnea, and exercise capacity) index and its
      components, arterial oxygenation (Pao(2)), inspiratory capacity (IC) to total
      lung capacity (TLC) ratio, and Charlson comorbidity score. We followed up the
      patients over time and evaluated the strength of the association between the
      variables and all-cause mortality. RESULTS: During the follow-up time (median, 36
      months; 25th to 75th percentiles, 24 to 50 months), 54 patients (25%) died. CRP
      levels were similar between survivors and the deceased (median, 3.8 mg/L; 95%
      confidence interval, 1.9 to 8.1; vs median, 4.5 mg/L; 95% confidence interval,
      2.1 to 11.5; p = 0.22) and was not significantly associated with survival.
      CONCLUSIONS: In this population of patients with clinically moderate to very
      severe COPD, the level of CRP level was not associated with survival compared
      with other prognostic clinical tools such as the BODE index, modified Medical
      Research Council scale, 6-min walk distance, percentage of predicted FEV(1),
      IC/TLC ratio < 0.25, and Pao(2). Other long-term studies of well-characterized
      patients with COPD could help determine the exact role of CRP levels as a
      biomarker in patients with clinical COPD.

PMID- 18339788
TI  - Secondhand tobacco smoke in children with asthma: sources of and parental
      perceptions about exposure in children and parental readiness to change.
AB  - BACKGROUND: Secondhand smoke triggers childhood asthma. Understanding sources of
      exposure, parental beliefs about exposure, and readiness to change that exposure
      are important for designing smoke exposure reduction interventions. METHODS: As
      part of screening for a clinical trial of a smoke exposure reduction
      intervention, 519 smoke-exposed children 3 to 12 years old with asthma provided
      urine specimens for cotinine testing, and their primary caregivers completed
      questionnaires. RESULTS: The urine cotinine to creatinine ratio (CCR) was lowest
      if neither the primary caregiver nor day-care provider smoked (mean CCR, 14.0;
      SD, 14.4), greater if either smoked (mean CCR, 22.2; SD, 21.3; and mean, CCR,
      26.3; SD, 22.2, respectively), and greatest if both smoked (mean CCR, 39.6; SD,
      27.5; p < 0.01). Parental perception of their child's exposure was weakly
      associated with the child's CCR (r(2) = 0.11, p < 0.001). Most parents (58.3%)
      reported that tobacco smoke exposure had small/no negative effect on their
      child's asthma. Substantial proportions of those for whom a specific exposure
      reduction action was relevant were classified as contemplating, preparing, or had
      recently taken action to reduce their child's exposure, including smoking
      cessation (61.3%), keeping the child out of smoke-exposed places (72.7%), and
      making the child's home (49.2%) and areas out of the home smoke free (66.9%).
      CONCLUSIONS: Smoking by the primary caregiver and day-care provider are important
      sources of exposure for children with asthma. Parental assessment of their
      child's exposure is associated with biologically confirmed exposure but cannot be
      relied on to assess that exposure. Although the harm of smoke exposure was
      frequently underestimated, many parents appeared receptive to considering action
      to reduce their child's exposure. TRIAL REGISTRATION: (Clinicaltrials.gov).
      Identifier: NCT00217958.

PMID- 18339789
TI  - Burden of concomitant asthma and COPD in a Medicaid population.
AB  - BACKGROUND: Asthma and COPD can significantly affect patients and pose a
      substantial economic burden for both patients and managed-care plans. This study
      compares utilization outcomes in patients with asthma, COPD, or co-occurring
      asthma and COPD in a Medicaid population, and assesses the incremental burden of
      COPD in patients with asthma. METHODS: We queried medical claims of Medicaid
      patients aged 40 to 64 years with asthma and/or COPD filed between January 1,
      2001, and December 31, 2003, from encounter data. COPD patients were identified
      based on at least one claim with International Classification of Diseases, Ninth
      Revision, Clinical Modification (ICD-9) codes 491, 492, 496; and asthma patients
      were identified on the basis of ICD-9 code 493 as diagnosis. We analyzed annual
      utilization and cost of hospitalizations, physician, and outpatient services
      attributable to asthma and/or COPD. RESULTS: The analysis included a total of
      3,072 asthma, 3,455 COPD, and 2,604 COPD/asthma patients. COPD/asthma co
      occurring disease has higher utilization of any service type than either disease
      alone. Compared with asthma patients, COPD patients were 16% and 51% more likely
      to use physician (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.01 to
      1.34) and inpatient services (OR, 1.51; 95% CI, 1.31 to 1.74), respectively; and
      60% less likely to use outpatient services (OR, 0.40; 95% CI, 0.35 to 0.46).
      Compared with asthma patients, COPD patients and COPD/asthma co-occurring
      patients cost 50% (OR, 1.50; 95% CI, 1.3 to 1.74) and five times (OR, 5.25; 95%
      CI, 4.59 to 6.02) more for total medical services, respectively. CONCLUSION: Our
      data suggest that patients with COPD and co-occurring COPD/asthma were sicker and
      used more medical services than asthma patients. The incremental burden of COPD
      to patients with asthma is significant.

PMID- 18339791
TI  - Pleural fluid analysis in chylous pleural effusion.
AB  - OBJECTIVES: Chyle is a noninflammatory, lymphocyte-predominant fluid that may
      cause a pleural effusion as a consequence of thoracic duct leakage into the
      pleural space. Although chyle is reported to have protein concentrations in the
      transudative range, chylous effusions are typically exudative, as defined by the
      standard criteria. We hypothesized that chylous effusions from a thoracic duct
      leak alone have low lactate dehydrogenase (LDH) concentrations due to the absence
      of inflammation and are lymphocyte-predominant, protein-discordant exudates.
      Consequently, pleural effusions that do not meet these criteria but with
      triglyceride concentrations of > 110 mg/dL or are positive for chylomicrons
      should be associated with other diagnoses contributing to pleural fluid
      formation. STUDY DESIGN: Retrospective. METHODS: The pleural fluid analyses of
      876 consecutive thoracenteses were reviewed. All cases with a triglyceride
      concentration of > 110 mg/dL or the presence of chylomicrons were retrieved. The
      effusions were then classified as transudates, concordant exudates, protein
      discordant exudates, and LDH-discordant exudates, and according to lymphocyte
      predominance (> 50%). The causes of these pleural effusions were determined after
      the review of the medical record. RESULTS: Twenty-two pleural effusions had
      elevated triglyceride concentrations and/or were positive for chylomicrons.
      Eleven effusions were lymphocyte-predominant, protein-discordant exudates, and
      two of these were associated with chylous ascites. The remaining effusions were
      transudates (n = 7) or concordant exudates (n = 4); all were associated with
      conditions known to cause pleural effusion apart from chyle leakage. CONCLUSION:
      Chylous effusions caused solely by conditions known to cause chylothorax were
      lymphocyte-predominant, protein-discordant exudates. Protein concentrations in
      the transudative range or elevated LDH concentrations were associated with a
      coexisting condition that may impact the management of these chylous effusions.

PMID- 18339790
TI  - Inhaled mannitol improves lung function in cystic fibrosis.
AB  - BACKGROUND: The airways in patients with cystic fibrosis (CF) are characterized
      by the accumulation of tenacious, dehydrated mucus that is a precursor for
      chronic infection, inflammation, and tissue destruction. The clearance of mucus
      is an integral component of daily therapy. Inhaled mannitol is an osmotic agent
      that increases the water content of the airway surface liquid, and improves the
      clearance of mucus with the potential to improve lung function and respiratory
      health. To this end, this study examined the efficacy and safety of therapy with
      inhaled mannitol over a 2-week period. METHODS: This was a randomized, double
      blind, placebo-controlled, crossover study. Thirty-nine subjects with mild-to
      moderate CF lung disease inhaled 420 mg of mannitol or placebo twice daily for 2
      weeks. Following a 2-week washout period, subjects were entered in the reciprocal
      treatment arm. Lung function, respiratory symptoms, quality of life, and safety
      were assessed. RESULTS: Mannitol treatment increased FEV(1) from baseline by a
      mean of 7.0% (95% confidence interval [CI], 3.3 to 10.7) compared to placebo 0.3%
      (95% CI, - 3.4 to 4.0; p < 0.001). The absolute improvement with mannitol therapy
      was 121 mL (95% CI, 56.3 to 185.7), which was significantly more than that with
      placebo (0 mL; 95% CI, - 64.7 to 64.7). The forced expiratory flow in the middle
      half of the FVC increased by 15.5% (95% CI, - 6.5 to 24.6) compared to that with
      placebo (increase, 0.7%; 95% CI, - 8.3 to 9.7; p < 0.02). The safety profile of
      mannitol was adequate, and no serious adverse events related to treatment were
      observed. CONCLUSIONS: Inhaled mannitol treatment over a period of 2 weeks
      significantly improved lung function in patients with CF. Mannitol therapy was
      safe and well tolerated. TRIAL REGISTRATION: (ClinicalTrials.gov) Identifier:
      NCT00455130.

PMID- 18339792
TI  - Use of B-type natriuretic peptide in the risk stratification of acute
      exacerbations of COPD.
AB  - BACKGROUND: In patients with COPD, prognosis might be determined at least in part
      by the extent of cardiac stress induced by hypoxia and pulmonary arterial
      hypertension. METHODS: B-type natriuretic peptide (BNP), a quantitative marker of
      cardiac stress, was determined in 208 consecutive patients presenting to the
      emergency department with an acute exacerbation of COPD (AECOPD). The accuracy of
      BNP to predict death at a 2-year follow-up was evaluated as the primary end
      point. The need for intensive care and in-hospital mortality were determined as
      secondary end points. RESULTS: BNP levels were significantly elevated during the
      acute exacerbation compared to recovery (65 pg/mL; interquartile range [IQR], 34
      to 189 pg/mL; vs 45 pg/mL; IQR, 25 to 85 pg/mL; p < 0.001), particularly in those
      patients requiring ICU treatment (105 pg/mL; IQR, 66 to 553 pg/mL; vs 60 pg/mL;
      IQR, 31 to 169 pg/mL; p = 0.007). In multivariate Cox regression analysis, BNP
      accurately predicted the need for ICU care (hazard ratio, 1.13; 95% confidence
      interval [CI], 1.03 to 1.24 for an increase in BNP of 100 pg/mL; p = 0.008). In a
      receiver operating characteristic analysis to evaluate the potential of BNP
      levels to predict short-term and long-term mortality rates, areas under the curve
      were 0.55 (SD, 0.71; 95% CI, 0.41 to 0.68) and 0.56 (SD, 0.53; 95% CI, 0.45 to
      0.66, respectively). CONCLUSIONS: In patients with AECOPD, BNP levels
      independently predict the need for intensive care. However, BNP levels failed to
      adequately predict short-term and long-term mortality rates in AECOPD patients.

PMID- 18339793
TI  - An evaluation of a titration strategy for prescription of oral appliances for
      obstructive sleep apnea.
AB  - BACKGROUND: Oral appliances (OAs) are first-line therapy for mild-to-moderate
      obstructive sleep apnea (OSA) and are being used with increasing frequency.
      Additionally, best practice of OA titration is unknown. We describe the
      experience of patients treated with an OA, identify factors that predict
      treatment success with an OA, and offer a protocol for OA titration. METHODS: We
      retrospectively studied patients seen in a dental sleep clinic between 2002 and
      2006. Patients selected for OA treatment underwent baseline polysomnography, were
      individually fit with an OA, and were instructed to titrate it at home until
      symptom resolution or discomfort. During follow-up polysomnography, additional
      titration was performed as needed. Primary outcome was successful treatment,
      defined as apnea-hypopnea index (AHI) <10 events per hour and AHI decrease at
      least 50% from baseline. Logistic regression models were created to identify
      associations between patient characteristics and successful treatment. Overall
      differences in AHI at baseline, after home titration, and after final titration
      were compared using Kruskal-Wallis test, and post hoc comparisons were performed
      with sign tests, with Bonferroni corrections. RESULTS: Of 57 subjects treated
      with an OA, 37 subjects (64.9%) were successfully treated with OA therapy. Of the
      49 subjects for whom data were available for AHI after home titration, 27
      subjects (55%) achieved successful treatment of OSA by self-titration, without
      need for further titration during follow-up polysomnography. CONCLUSIONS: A
      majority of subjects, regardless of OSA severity, are successfully treated with
      an OA. Men and younger patients were found to be the best responders. The
      titration protocol for an OA offers a beneficial initial step in the treatment of
      OSA.

PMID- 18339794
TI  - Association of sleep-disordered breathing with postoperative complications.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased
      perioperative risk, but the incidence of postoperative complications and the
      severity of OSA associated with increased risk have not been established. We
      investigated the relationship between intermittent hypoxemia measured by home
      nocturnal oximetry with the occurrence of postoperative complications in patients
      with clinical signs of OSA identified during preoperative assessment for elective
      surgery. METHODS: This study was performed at a tertiary care hospital. Home
      nocturnal oximetry was performed on elective surgical patients with clinical
      features of OSA. The number of episodes per hour of oxygen desaturation (or
      oxygen desaturation index) of > or = 4% (ODI4%) was determined. Subjects with
      five or more desaturations per hour (ODI4% > or = 5) were compared to those with
      less than five desaturations per hour (ODI4% < 5). Hospital records were reviewed
      to assess the incidence and type of postoperative complications. RESULTS: A total
      of 172 patients were investigated as part of this study. No significant
      differences were observed between groups in terms of age, body mass index, number
      of medical comorbidities, or smoking history. Patients with an ODI4% > or = 5 had
      a significantly higher rate of postoperative complications than those with ODI4%
      < 5 (15.3% vs 2.7%, respectively [p < 0.01]; adjusted odds ratio, 7.2; 95%
      confidence interval, 1.5 to 33.3 [p = 0.012]). The complication rate also
      increased with increasing ODI severity (patients with an ODI4% of 5 to 15 events
      per hour, 13.8%; patients with an ODI4% of > or = 15 events per hour, 17.5%; p =
      0.01) Complications were respiratory (nine patients), cardiovascular (five
      patients), GI (one patient), and bleeding (two patients). The hospital length of
      stay was similar in both groups. CONCLUSION: An ODI4%> or = 5, determined by home
      nocturnal oximetry, in patients with clinical features of OSA is associated with
      an increased rate of postoperative complications.

PMID- 18339795
TI  - Discovery and verification of head-and-neck cancer biomarkers by differential
      protein expression analysis using iTRAQ labeling, multidimensional liquid
      chromatography, and tandem mass spectrometry.
AB  - Multidimensional LC-MS/MS has been used for the analysis of biological samples
      labeled with isobaric mass tags for relative and absolute quantitation (iTRAQ) to
      identify proteins that are differentially expressed in human head-and-neck
      squamous cell carcinomas (HNSCCs) in relation to non-cancerous head-and-neck
      tissues (controls) for cancer biomarker discovery. Fifteen individual samples
      (cancer and non-cancerous tissues) were compared against a pooled non-cancerous
      control (prepared by pooling equal amounts of proteins from six non-cancerous
      tissues) in five sets by on-line and off-line separation. We identified 811 non
      redundant proteins in HNSCCs, including structural proteins, signaling
      components, enzymes, receptors, transcription factors, and chaperones. A panel of
      proteins showing consistent differential expression in HNSCC relative to the non
      cancerous controls was discovered. Some of the proteins include stratifin (14-3
      3sigma); YWHAZ (14-3-3zeta); three calcium-binding proteins of the S100 family,
      S100-A2, S100-A7 (psoriasin), and S100-A11 (calgizarrin); prothymosin alpha
      (PTHA); L-lactate dehydrogenase A chain; glutathione S-transferase Pi; APC
      binding protein EB1; and fascin. Peroxiredoxin2, carbonic anhydrase I, flavin
      reductase, histone H3, and polybromo-1D (BAF180) were underexpressed in HNSCCs. A
      panel of the three best performing biomarkers, YWHAZ, stratifin, and S100-A7,
      achieved a sensitivity of 0.92 and a specificity of 0.91 in discriminating
      cancerous from non-cancerous head-and-neck tissues. Verification of differential
      expression of YWHAZ, stratifin, and S100-A7 proteins in clinical samples of
      HNSCCs and paired and non-paired non-cancerous tissues by immunohistochemistry,
      immunoblotting, and RT-PCR confirmed their overexpression in head-and-neck
      cancer. Verification of YWHAZ, stratifin, and S100-A7 in an independent set of
      HNSCCs achieved a sensitivity of 0.92 and a specificity of 0.87 in discriminating
      cancerous from non-cancerous head-and-neck tissues, thereby confirming their
      overexpressions and utility as credible cancer biomarkers.

PMID- 18339796
TI  - Muscle activation during selected strength exercises in women with chronic neck
      muscle pain.
AB  - BACKGROUND AND PURPOSE: Muscle-specific strength training has previously been
      shown to be effective in the rehabilitation of chronic neck muscle pain in women.
      The aim of this study was to determine the level of activation of the neck and
      shoulder muscles using surface electromyography (EMG) during selected
      strengthening exercises in women undergoing rehabilitation for chronic neck
      muscle pain (defined as a clinical diagnosis of trapezius myalgia). SUBJECTS: The
      subjects were 12 female workers (age=30-60 years) with a clinical diagnosis of
      trapezius myalgia and a mean baseline pain intensity of 5.6 (range=3-8) on a
      scale of 0 to 9. METHOD: Electromyographic activity in the trapezius and deltoid
      muscles was measured during the exercises (lateral raises, upright rows, shrugs,
      one-arm rows, and reverse flys) and normalized to EMG activity recorded during a
      maximal voluntary static contraction (MVC). RESULTS: For most exercises, the
      level of muscle activation was relatively high (>60% of MVC), highlighting the
      effectiveness and specificity of the respective exercises. For the trapezius
      muscle, the highest level of muscle activation was found during the shrug (102+/
      11% of MVC), lateral raise (97+/-6% of MVC), and upright row (85+/-5% of MVC)
      exercises, but the latter 2 exercises required smaller training loads (3-10 kg)
      compared with the shrug exercise (20-30 kg). DISCUSSION AND CONCLUSION: The
      lateral raise and upright row may be suitable alternatives to shrugs during
      rehabilitation of chronic neck muscle pain. Several of the strength exercises had
      high activation of neck and shoulder muscles in women with chronic neck pain.
      These exercises can be used equally in the attempt to achieve a beneficial
      treatment effect on chronic neck muscle pain.

PMID- 18339797
TI  - Motor learning in children: feedback effects on skill acquisition.
AB  - BACKGROUND AND PURPOSE: Reduced feedback during motor skill practice benefits
      motor learning. However, it is unknown whether these findings can be applied to
      motor learning in children, given that children have different information
      processing capabilities than adults. The purpose of this study was to determine
      the effect of different relative frequencies of feedback on skill acquisition in
      children compared with young adults. SUBJECTS: The participants were 20 young
      adults and 20 children. METHODS: All participants practiced 200 trials of a
      discrete arm movement with specific spatiotemporal parameters. Participants from
      each group (adults and children) were randomly assigned to either a 100% feedback
      group or a reduced (62% faded) feedback group. Learning was inferred from the
      performance on the delayed (24-hour) retention and reacquisition tests. RESULTS:
      All participants improved accuracy and consistency across practice trials. During
      practice, the adults performed with significantly less error than the children.
      Adults who practiced with reduced feedback performed with increased consistency
      during the retention test compared with those who practiced with 100% feedback.
      In contrast, children who received reduced feedback during practice performed
      with less accuracy and consistency during the retention test than those who
      received 100% feedback. However, when feedback was reintroduced during the
      reacquisition test, the children in the reduced feedback group were able to
      improve their performance comparable to those in the 100% feedback group.
      DISCUSSION AND CONCLUSION: During motor learning, children use feedback in a
      manner different from that of adults. To optimize motor learning, children may
      require longer periods of practice, with feedback reduced more gradually,
      compared with young adults.

PMID- 18339798
TI  - Validity of values for metabolic equivalents of task during submaximal all
      extremity exercise and reliability of exercise responses in frail older adults.
AB  - BACKGROUND AND PURPOSE: Physical therapists and rehabilitation professionals in
      hospital and long-term care centers are using all-extremity semirecumbent
      exercise machines in their treatment programs. This study was undertaken to
      investigate the concurrent validity of values for software-generated metabolic
      equivalents of task (MET) from an all-extremity semirecumbent exercise machine
      and directly measured values for MET from a portable metabolic unit across a
      range of submaximal exercise intensities. A second purpose of this study was to
      determine the test-retest reliability of oxygen consumption and heart rate
      responses in older adults between standardized sessions of submaximal all
      extremity aerobic exercise. SUBJECTS AND METHODS: The study participants were 18
      older adults (mean age=82 years, SD=5; 3 women, 15 men) who were living in long
      term care centers and who completed 2 test sessions of a standardized exercise
      protocol 1 week apart. The exercise protocol included a warm-up period, three 4
      minute stages of exercise at incremental workload levels, and a cool-down period.
      The breath-by-breath metabolic data from the portable metabolic unit, heart rate,
      MET values from the exercise machine, Borg Rating of Perceived Exertion, and
      watts were recorded continuously throughout the exercise protocol. RESULTS: The
      concurrent validity of the MET values from the exercise machine and the portable
      metabolic unit ranged from very good to excellent on both day 1 and day 2 (r=.85
      .97). The test-retest reliability of subjects' heart rate responses and MET
      values from the portable metabolic unit was moderate to high across submaximal
      exercise intensities (intraclass correlation coefficients [2,1]=.85-.91).
      DISCUSSION AND CONCLUSION: The exercise machine software-generated MET values
      were representative of directly measured oxygen consumption values across a range
      of submaximal intensities during all-extremity semirecumbent exercise in older
      adults with multisystem impairments.

PMID- 18339799
TI  - Reference curves for the Gross Motor Function Measure: percentiles for clinical
      description and tracking over time among children with cerebral palsy.
AB  - BACKGROUND AND PURPOSE: Physical therapists frequently use the 66-item Gross
      Motor Function Measure (GMFM-66) with the Gross Motor Function Classification
      System (GMFCS) to examine gross motor function in children with cerebral palsy
      (CP). Until now, reference percentiles for this measure were not available. The
      aim of this study was to improve the clinical utility of this gross motor measure
      by developing cross-sectional reference percentiles for the GMFM-66 within levels
      of the GMFCS. SUBJECTS AND METHODS: A total of 1,940 motor measurements from 650
      children with CP were used to develop percentiles. These observations were taken
      from a subsample, stratified by age and GMFCS, of those in a longitudinal cohort
      study reported in 2002. A standard LMS (skewness-median-coefficient of variation)
      method was used to develop cross-sectional reference percentiles. RESULTS:
      Reference curves were created for the GMFM-66 by age and GMFCS level, plotted at
      the 3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97th percentiles. The
      variability of change in children's percentiles over a 1-year interval also was
      investigated. DISCUSSION AND CONCLUSION: The reference percentiles extend the
      clinical utility of the GMFM-66 and GMFCS by providing for appropriate normative
      interpretation of GMFM-66 scores within GMFCS levels. When interpreting change in
      percentiles over time, therapists must carefully consider the large variability
      in change that is typical among children with CP. The use of percentiles should
      be supplemented by interpretation of the raw scores to understand change in
      function as well as relative standing.

PMID- 18339800
TI  - British American Tobacco ghost-wrote reports on tobacco advertising bans by the
      International Advertising Association and J J Boddewyn.
AB  - In 1983 and 1986, the International Advertising Association (IAA) published an
      original version and then a revision of a report entitled "Tobacco Advertising
      Bans and Consumption in 16 Countries," which were edited by J J Boddewyn, a
      marketing professor. The reports concluded that tobacco advertising bans have not
      been accompanied by any significant reduction in tobacco consumption. Opponents
      of tobacco advertising restrictions trumpeted the IAA reports in print materials,
      media communications and legislative hearings during the 1980s and beyond. A new
      analysis of tobacco industry documents and transcripts of tobacco litigation
      testimony reveals that British American Tobacco ghost-wrote the IAA reports and
      that the Tobacco Institute (the trade association then representing the major US
      cigarette manufacturers) helped to arrange for Boddewyn to present the findings
      to the US Congress and the media. Further research on tobacco industry documents
      and tobacco litigation transcripts should assess whether tobacco industry sources
      were responsible for ghost-writing other studies favourable to the industry.

PMID- 18339801
TI  - Maintenance of the plasma cell pool is independent of memory B cells.
AB  - Humoral memory to an antigen (Ag) is maintained for several decades in the form
      of memory B cells and serum Ab. In fact, plasma cells (PCs) that secrete Ab are
      known to be long-lived and could be solely responsible for maintaining the long
      lived Ab titers. Alternatively, it has been proposed that the PC compartment is
      maintained for long periods by the differentiation of memory cells into long
      lived PCs as a result of nonspecific stimulation. This model predicts accelerated
      decay of PC numbers in the absence of memory cells for the same Ag. To address
      this prediction, we have developed a mouse model system that combined the ability
      to deplete B cells with the ability to detect Ag-specific memory and PCs. After
      establishing an immune response, we depleted Ag-specific memory B cells with an
      anti-hCD20 mAb and determined the effect on the PC compartment over 16 weeks.
      Using a combination of surface markers, we demonstrated that memory B cells
      remained depleted over the course of the experiment. However, despite this
      absence of memory cells for an extended duration, PC numbers in spleen and bone
      marrow did not decline, which indicates that the PC compartment does not require
      a significant contribution from memory B cells for its maintenance and instead
      that PCs are sufficiently long-lived to maintain Ab titers over a long period
      without renewal. This observation settles an important controversy in B cell
      biology and has implications for the design of vaccines and for B cell depletion
      therapy in patients.

PMID- 18339802
TI  - Inositol trisphosphate 3-kinase B (InsP3KB) as a physiological modulator of
      myelopoiesis.
AB  - Inositol trisphosphate 3-kinase B (InsP3KB) belongs to a family of kinases that
      convert inositol 1,4,5-trisphosphate (Ins(1,4,5)P3 or IP3) to inositol 1,3,4,5
      tetrakisphosphate (Ins(1,3,4,5)P4). Previous studies have shown that disruption
      of InsP3KB leads to impaired T cell and B cell development as well as
      hyperactivation of neutrophils. Here, we demonstrate that InsP3KB is also a
      physiological modulator of myelopoiesis. The InsP3KB gene is expressed in all
      hematopoietic stem/progenitor cell populations. In InsP3KB null mice, the bone
      marrow granulocyte monocyte progenitor (GMP) population was expanded, and GMP
      cells proliferated significantly faster. Consequently, neutrophil production in
      the bone marrow was enhanced, and the peripheral blood neutrophil count was also
      substantially elevated in these mice. These effects might be due to enhancement
      of PtdIns(3,4,5)P3/Akt signaling in the InsP3KB null cells. Phosphorylation of
      cell cycle-inhibitory protein p21(cip1), one of the downstream targets of Akt,
      was augmented, which can lead to the suppression of the cell cycle-inhibitory
      effect of p21.

PMID- 18339803
TI  - X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells.
AB  - With the potential to give rise to all somatic cell types, human embryonic stem
      cells (hESC) have generated enormous interest as agents of cell replacement
      therapy. One potential limitation is their safety in vivo. Although several
      studies have focused on concerns over genomic stability ex vivo, few have
      analyzed epigenetic stability. Here, we use tools of the epigenetic phenomenon, X
      chromosome inactivation (XCI), to investigate their epigenetic properties. Among
      11 distinct hESC lines, we find a high degree of variability. We show that, like
      mouse ESC, hESC in principle have the capacity to recapitulate XCI when induced
      to differentiate in culture (class I lines). However, this capacity is seen in
      few hESC isolates. Many hESC lines have already undergone XCI (class II and III).
      Unexpectedly, there is a tendency to lose XIST RNA expression during culture
      (class III). Despite losing H3-K27 trimethylation, the inactive X of class III
      lines remains transcriptionally suppressed, as indicated by Cot-1 RNA exclusion.
      We conclude that hESC lines are subject to dynamic epigenetic reprogramming ex
      vivo. Given that XCI and cell differentiation are tightly linked, we consider
      implications for hESC pluripotency and differentiation potential.

PMID- 18339804
TI  - X-inactivation in female human embryonic stem cells is in a nonrandom pattern and
      prone to epigenetic alterations.
AB  - X chromosome inactivation (XCI) is an essential mechanism for dosage compensation
      of X-linked genes in female cells. We report that subcultures from lines of
      female human embryonic stem cells (hESCs) exhibit variation (0-100%) for XCI
      markers, including XIST RNA expression and enrichment of histone H3 lysine 27
      trimethylation (H3K27me3) on the inactive X chromosome (Xi). Surprisingly,
      regardless of the presence or absence of XCI markers in different cultures, all
      female hESCs we examined (H7, H9, and HSF6 cells) exhibit a monoallelic
      expression pattern for a majority of X-linked genes. Our results suggest that
      these established female hESCs have already completed XCI during the process of
      derivation and/or propagation, and the XCI pattern of lines we investigated is
      already not random. Moreover, XIST gene expression in subsets of cultured female
      hESCs is unstable and subject to stable epigenetic silencing by DNA methylation.
      In the absence of XIST expression, approximately 12% of X-linked promoter CpG
      islands become hypomethylated and a portion of X-linked alleles on the Xi are
      reactivated. Because alterations in dosage compensation of X-linked genes could
      impair somatic cell function, we propose that XCI status should be routinely
      checked in subcultures of female hESCs, with cultures displaying XCI markers
      better suited for use in regenerative medicine.

PMID- 18339805
TI  - Reassessing a sparse energetic network within a single protein domain.
AB  - Understanding the molecular principles that govern allosteric communication is an
      important goal in protein science. One way allostery could be transmitted is via
      sparse energetic networks of residues, and one such evolutionary conserved
      network was identified in the PDZ domain family of proteins by multiple sequence
      alignment [Lockless SW, Ranganathan R (1999) Science 286:295-299]. We have
      reassessed the energetic coupling of these residues by double mutant cycles
      together with ligand binding and stability experiments and found that coupling is
      not a special property of the coevolved network of residues in PDZ domains. The
      observed coupling for ligand binding is better explained by a distance
      relationship, where residues close in space are more likely to couple than distal
      residues. Our study demonstrates that statistical coupling from sequence analysis
      is not necessarily a reporter of energetic coupling and allostery.

PMID- 18339806
TI  - Herbivory-induced changes in the small-RNA transcriptome and phytohormone
      signaling in Nicotiana attenuata.
AB  - Phytohormones mediate the perception of insect-specific signals and the
      elicitation of defenses during insect attack. Large-scale changes in a plant's
      transcriptome ensue, but how these changes are regulated remains unknown.
      Silencing of RNA-directed RNA polymerase 1 (RdR1) makes Nicotiana attenuata
      highly susceptible to insect herbivores, suggesting that defense elicitation is
      under the direct control of small-RNAs (smRNAs). Using 454-sequencing, we
      characterized N. attenuata's smRNA transcriptome before and after insect-specific
      elicitation in wild-type (WT) and RdR1-silenced (irRdR1) plants. We predicted the
      targets of N. attenuata smRNAs in the genes related to phytohormone signaling
      (jasmonic acid, JA-Ile, and ethylene) known to mediate resistance responses, and
      we measured the elicited dynamics of phytohormone biosynthetic transcripts and
      phytohormone levels in time-course experiments with field- and glasshouse-grown
      plants. RdR1 silencing severely altered the induced transcript accumulation of 8
      of the 10 genes, reduced JA, and enhanced ethylene levels after elicitation.
      Adding JA completely restored the insect resistance of irRdR1 plants. irRdR1
      plants had photosynthetic rates, growth, and reproductive output
      indistinguishable from that of WT plants, suggesting unaltered primary
      metabolism. We conclude that the susceptibility of irRdR1 plants to herbivores is
      due to altered phytohormone signaling and that smRNAs play a central role in
      coordinating the large-scale transcriptional changes that occur after herbivore
      attack. Given the diversity of smRNAs that are elicited after insect attack and
      the recent demonstration of the ability of ingested smRNAs to silence transcript
      accumulation in lepidopteran larvae midguts, the smRNA responses of plants may
      also function as direct defenses.

PMID- 18339807
TI  - Role of the Akt pathway in mRNA translation of interferon-stimulated genes.
AB  - Multiple signaling pathways are engaged by the type I and II IFN receptors, but
      their specific roles and possible coordination in the generation of IFN-mediated
      biological responses remain unknown. We provide evidence that activation of Akt
      kinases is required for IFN-inducible engagement of the mTOR/p70 S6 kinase
      pathway. Our data establish that Akt activity is essential for up-regulation of
      key IFN-alpha- and IFN-gamma-inducible proteins, which have important functional
      consequences in the induction of IFN responses. Such effects of the Akt pathway
      are unrelated to regulatory activities on IFN-dependent STAT
      phosphorylation/activation or transcriptional regulation. By contrast, they
      reflect regulatory activities on mRNA translation via direct control of the mTOR
      pathway. In studies using Akt1 and Akt2 double knockout cells, we found that the
      absence of Akt kinases results in dramatic reduction in IFN-induced antiviral
      responses, establishing a critical role of the Akt pathway in IFN signaling.
      Thus, activation of the Akt pathway by the IFN receptors complements the function
      of IFN-activated JAK-STAT pathways, by allowing mRNA translation of IFN
      stimulated genes and, ultimately, the induction of the biological effects of
      IFNs.

PMID- 18339808
TI  - Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum
      requires Ryp1, a conserved transcriptional regulator.
AB  - Histoplasma capsulatum, a fungal pathogen of humans, switches from a filamentous
      spore-forming mold in the soil to a pathogenic budding-yeast form in the human
      host. This morphologic switch, which is exhibited by H. capsulatum and a group of
      evolutionarily related fungal pathogens, is regulated by temperature. Using
      insertional mutagenesis, we identified a gene, RYP1 (required for yeast phase
      growth), which is required for yeast-form growth at 37 degrees C. ryp1 mutants
      are constitutively filamentous irrespective of temperature. Ryp1 is a member of a
      family of fungal proteins that includes Wor1, a master transcriptional regulator
      of the white-opaque transition required for mating in Candida albicans. Ryp1
      associates with its own upstream regulatory region, consistent with a direct role
      in transcriptional control, and both the protein and its transcript accumulate to
      high levels in wild-type yeast-phase cells. Microarray analysis demonstrated that
      Ryp1 is required for the expression of the vast majority of yeast-specific genes,
      including two genes linked to virulence. Thus, Ryp1 appears to be a critical
      transcriptional regulator of a temperature-regulated morphologic switch in H.
      capsulatum.

PMID- 18339809
TI  - Genetic royal cheats in leaf-cutting ant societies.
AB  - Social groups are vulnerable to cheating because the reproductive interests of
      group members are rarely identical. All cooperative systems are therefore
      predicted to involve a mix of cooperative and cheating genotypes, with the
      frequency of the latter being constrained by the suppressive abilities of the
      former. The most significant potential conflict in social insect colonies is over
      which individuals become reproductive queens rather than sterile workers. This
      reproductive division of labor is a defining characteristic of eusocial
      societies, but individual larvae will maximize their fitness by becoming queens
      whereas their nestmates will generally maximize fitness by forcing larvae to
      become workers. However, evolutionary constraints are thought to prevent cheating
      by removing genetic variation in caste propensity. Here, we show that one-fifth
      of leaf-cutting ant patrilines cheat their nestmates by biasing their larval
      development toward becoming queens rather than workers. Two distinct mechanisms
      appear to be involved, one most probably involving a general tendency to become a
      larger adult and the other relating specifically to the queen-worker
      developmental switch. Just as evolutionary theory predicts, these "royal"
      genotypes are rare both in the population and within individual colonies. The
      rarity of royal cheats is best explained as an evolutionary strategy to avoid
      suppression by cooperative genotypes, the efficiency of which is frequency
      dependent. The results demonstrate that cheating can be widespread in even the
      most cooperative of societies and illustrate that identical principles govern
      social evolution in highly diverse systems.

PMID- 18339810
TI  - Vesicle association and exocytosis at ribbon and extraribbon sites in retinal
      bipolar cell presynaptic terminals.
AB  - Synaptic vesicles release neurotransmitter by following a process of vesicle
      docking and exocytosis. Although these steps are well established, it has been
      difficult to observe and measure these rates directly in living synapses. Here,
      by combining the direct imaging of single synaptic vesicles and synaptic ribbons,
      I measure the properties of vesicle docking and evoked and spontaneous release
      from ribbon and extraribbon locations in a ribbon-type synaptic terminal, the
      goldfish retinal bipolar cell. In the absence of a stimulus, captured vesicles
      near ribbons associate tightly and only rarely undock or undergo spontaneous
      exocytosis. By contrast, vesicle capture at outlier sites is less stable and
      spontaneous exocytosis occurs at a higher rate. In response to a stimulus,
      exocytic events cluster near ribbons, but show no evidence of clustering away
      from ribbon sites. Together, the results here indicate that, although vesicles
      can associate and fuse both near and away from synaptic sites, vesicles at
      synaptic ribbons associate more stably and fusion is more tightly linked to
      stimuli.

PMID- 18339811
TI  - Protein phosphatase 2A controls the activity of histone deacetylase 7 during T
      cell apoptosis and angiogenesis.
AB  - Class IIa histone deacetylases (HDACs) act as key transcriptional regulators in
      several important developmental programs. Their activities are controlled via
      phosphorylation-dependent nucleocytoplasmic shuttling. Phosphorylation of
      conserved serine residues triggers association with 14-3-3 proteins and
      cytoplasmic relocalization of class IIa HDACs, which leads to the derepression of
      their target genes. Although a lot of effort has been made toward the
      identification of the inactivating kinases that phosphorylate class IIa HDAC 14-3
      3 motifs, the existence of an antagonistic protein phosphatase remains elusive.
      Here we identify PP2A as a phosphatase responsible for dephosphorylating the 14-3
      3 binding sites in class IIa HDACs. Interestingly, dephosphorylation of class IIa
      HDACs by PP2A is prevented by competitive association of 14-3-3 proteins. Using
      both okadaic acid treatment and RNA interference, we demonstrate that PP2A
      constitutively dephosphorylates the class IIa member HDAC7 to control its
      biological functions as a regulator of T cell apoptosis and endothelial cell
      functions. This study unravels a dynamic interplay among 14-3-3s, protein
      kinases, and PP2A and provides a model for the regulation of class IIa HDACs.

PMID- 18339812
TI  - Transposition of a reconstructed Harbinger element in human cells and functional
      homology with two transposon-derived cellular genes.
AB  - Ancient, inactive copies of transposable elements of the PIF/Harbinger
      superfamily have been described in vertebrates. We reconstructed components of
      the Harbinger3_DR transposon in zebrafish, including a transposase and a second,
      transposon-encoded protein that has a Myb-like trihelix domain. The reconstructed
      Harbinger transposon shows efficient cut-and-paste transposition in human cells
      and preferentially inserts into a 15-bp consensus target sequence. The Myb-like
      protein is required for transposition and physically interacts with the N
      terminal region of the transposase via its C-terminal domain. The Myb-like
      protein enables transposition in part by promoting nuclear import of the
      transposase, by directly binding to subterminal regions of the transposon, and by
      recruiting the transposase to the transposon ends. We investigated the functions
      of two transposon-derived human proteins: HARBI1, a domesticated transposase
      derived protein, and NAIF1, which contains a trihelix motif similar to that
      described in the Myb-like protein. Physical interaction, subcellular
      localization, and DNA-binding activities of HARBI1 and NAIF1 suggest strong
      functional homologies between the Harbinger3_DR system and their related, host
      encoded counterparts. The Harbinger transposon will serve as a useful
      experimental system for transposon biology and for investigating the enzymatic
      functions of domesticated, transposon-derived cellular genes.

PMID- 18339813
TI  - Neurobiology and treatment in alcoholism--recent findings regarding Lesch's
      typology of alcohol dependence.
AB  - Subtyping in alcohol dependence has become an important issue as studies have
      proposed different neurobiological mechanisms in alcoholism in the recent years.
      Studies have shown that alcohol dependence reflects a wide range of different
      phenotypes, including psychological, social, and neurobiological factors.
      Different ways of subtyping have been proposed in the last decades, one of them
      being Lesch's typology of alcohol dependence. Recent investigations have shown
      that different subtypes of Lesch's typology are associated with specific
      neurobiological factors which may have important implications for clinical
      practice. This applies in particular for genetic and neuroendocrinological
      factors, differences in the regulation of NMDA receptor-mediated glutamatergic
      neurotransmission, and in response to acamprosate and naltrexone treatment.

PMID- 18339814
TI  - Involvement of multidrug resistance-associated protein 2 (Abcc2) in molecular
      weight-dependent biliary excretion of beta-lactam antibiotics.
AB  - In the present study, we attempted to identify the membrane permeation
      process(es) primarily involved in the molecular-weight-dependent biliary
      excretion of beta-lactam antibiotics. A search of the literature indicated that
      the molecular weight threshold operates mainly in the transport process across
      bile canalicular membranes. We confirmed that biliary clearance of the model
      biliary-excretion-type cephalosporin cefoperazone was reduced to 10% of the
      control in Eisai hyperbilirubinemic rats, which are genetically deficient in
      multidrug resistance-associated protein (Mrp) 2, indicating that Mrp2 plays a
      major role as an efflux transporter on the canalicular membranes. ATP-dependent
      uptake of several cephalosporins including cefoperazone, cefbuperazone,
      cefpiramide, and ceftriaxone, all of which are mainly excreted into bile, was
      confirmed in membrane vesicles from Sf9 cells transfected with rat Mrp2. Both the
      inhibitory potency of the cephalosporins for Mrp2-mediated transport and the
      uptake of cephalosporins by Mrp2-expressing vesicles were molecular weight
      dependent, suggesting that Mrp2 is one of the major transporters involved in
      molecular weight-dependent biliary excretion. An uptake study in membrane
      vesicles of Sf9 cells transfected with breast cancer resistance protein (Bcrp)
      revealed that Bcrp accepts cefoperazone, cefbuperazone, cefpiramide, cefotetan,
      ceftriaxone, cefotiam, cefamandole, and cefazolin as substrates, and Bcrp
      mediated transport was also molecular weight-dependent, suggesting that Bcrp also
      contributes to molecular weight-dependent biliary excretion of beta-lactam
      antibiotics in rats.

PMID- 18339815
TI  - Hydroxyitraconazole, formed during intestinal first-pass metabolism of
      itraconazole, controls the time course of hepatic CYP3A inhibition and the
      bioavailability of itraconazole in rats.
AB  - Itraconazole (ITZ) is a substrate of CYP3A and both ITZ and hydroxyitraconazole
      (OH-ITZ), a major metabolite formed by CYP3A, are potent inhibitors of CYP3A. The
      concentration- and time-dependent changes in the hepatic availability (F(H)) of
      ITZ were evaluated in rats after oral doses of 5 and 40 mg/kg. Simultaneous blood
      samples were obtained from the aorta, portal vein, and hepatic vein for 24 h
      following duodenal ITZ administration, and concentrations of ITZ and OH-ITZ
      determined by LC/MS. During the absorption phase, the F(H) of ITZ increased from
      0.2 to 1.0, reflecting the time course of hepatic CYP3A inhibition. A
      counterclockwise hysteresis was observed between ITZ concentrations entering the
      liver (C(IN,ITZ)) and F(H), whereas there was no time delay observed between the
      change in F(H) and the OH-ITZ concentrations entering the liver (C(IN,OH-ITZ)).
      The direct relationship between C(IN,OH-ITZ) and F(H) suggested that OH-ITZ was
      mainly responsible for the inhibition of CYP3A. A positive portal venous-aortic
      gradient for OH-ITZ was measured after duodenal administration of ITZ, indicating
      intestinal formation of OH-ITZ. The in vivo Ki for OH-ITZ (38 +/- 3 nM) was
      estimated from C(IN,OH-ITZ) versus F(H) of ITZ, and is similar to values obtained
      from inhibition of midazolam hydroxylation in CYP3A4 supersomes (Drug Metab
      Dispos 32:1121-1131, 2004). The data suggest that OH-ITZ, formed by intestinal
      CYP3A, controls the time course of hepatic CYP3A inhibition and is mainly
      responsible for the observed increase in F(H) of ITZ.

PMID- 18339816
TI  - Forkhead box A2-mediated regulation of female-predominant expression of the mouse
      Cyp2b9 gene.
AB  - The regulation mechanism of female-predominant expression of the mouse Cyp2b9
      gene was investigated in vivo and in vitro. Luciferase reporter assay revealed
      that the -234/-194 region of the Cyp2b9 gene may be responsible for sexually
      dimorphic expression. There is a predicted forkhead box A2 (FoxA2) (hepatic
      nuclear factor 3beta)-binding site in this region. Chromatin immunoprecipitation
      assay indicated that the binding protein to the site was FoxA2 in 5-week-old
      female mice, whereas this protein was found in both sexes at age 3 weeks, in
      accordance with our previous observation on the developmental expression of this
      gene. Mutation of the predicted FoxA2 site in the reporter construct containing
      the -234/+18 fragment led to complete elimination of luciferase activity, but
      deletion of the -234/-194 region resulted in considerable transcriptional
      activity, suggesting that by mutating the FoxA2-binding site a potent suppressor
      might bind to eliminate activity, whereas by deleting this region it could not.
      Sexually dimorphic secretion of growth hormone is involved in female-predominant
      expression of the gene, and the -234/-194 region was also responsible for
      suppressing the expression by male-type secretion.

PMID- 18339817
TI  - Welfare regime types and global health: an emerging challenge.

PMID- 18339818
TI  - Debates about cervical screening: an historical overview.

PMID- 18339819
TI  - Neighbourhood environment as a predictor of television watching among girls.
AB  - BACKGROUND: Television watching, a sedentary activity, has been associated with
      overweight in children. While the family environment is known to influence
      television watching, little is known about the influence of the neighbourhood
      environment. This study is an exploratory examination of the association of
      socioeconomic characteristics of the neighbourhood environment with television
      watching among 9-10 year old girls. METHODS: Data collected by the Berkeley site
      of the National Heart, Lung and Blood Institute Growth and Health Study (NGHS) in
      1987-8 from 787 girls who had a complete set of measurements relevant to the
      analysis were used. These measures included parental education, household income,
      race and weekly hours spent watching television. Addresses of the girls were
      geocoded and the median household income for the census tracts in which they
      lived was used to indicate neighbourhood socioeconomic characteristics.
      Multilevel modelling procedures were used to estimate fixed effect coefficients
      for individual and neighbourhood level variables. RESULTS: Living in high income
      areas was associated with less television watching, a finding that held even when
      controlling for parental education, household income and race. Race and parental
      education were also associated with television watching. CONCLUSION: Television
      watching among girls was associated not only with the socioeconomic
      characteristics of their households, but also of their neighbourhoods. Future
      studies should explore the mechanisms that mediate this relation and determine if
      these results are generalisable to other populations.

PMID- 18339820
TI  - Home ownership and mortality: a register-based follow-up study of 300,000 Finns.
AB  - BACKGROUND: This study examined whether living in rented housing is associated
      with increased all-cause and cause-specific mortality, and whether the
      association between home ownership and mortality can be explained by household
      income, occupational class, and educational level. METHODS: A random sample
      including every seventh Finn aged 40-80 years at the end of 1997 (N = 308 291)
      was derived from the population register of Finland. The sample was followed up
      for mortality until the end of 2003 during which time there were 22,721 deaths.
      RESULTS: The hazard ratio for all-cause mortality among renters compared with
      owner-occupiers was 2.06 (95% CI 1.98 to 2.14) in men and 1.73 (1.65 to 1.81) in
      women. Adjusting for household income, occupational class, and educational level
      attenuated the excess mortality among renters by 30% in men and 19% in women. The
      effect of income was larger among the under 65 year olds than those aged 65 years
      or over. Excess mortality among renters was particularly high for alcohol-related
      diseases, respiratory diseases, lung cancer, as well as endocrine, metabolic and
      nutritional diseases, and infections. CONCLUSIONS: Renters had higher mortality
      than owner-occupiers even after adjusting for household income, occupational
      class, and educational level. Home ownership may indicate material living
      standards and cumulative wealth that cannot sufficiently be captured by
      conventional socioeconomic indicators. Analysing home ownership may thus increase
      understanding of the factors producing inequalities in health.

PMID- 18339821
TI  - Tackling inequalities in health: evaluating the New Deal for Communities
      initiative.
AB  - OBJECTIVE: To assess health improvement and differential changes in health across
      various sociodemographic groups in neighbourhood renewal areas. DESIGN AND
      SETTING: A longitudinal survey of 10,390 residents in New Deal for Communities
      (NDC) areas and 977 residents in comparator areas in England. Measures and
      methods: Changes on several outcomes across five domains (health, unemployment,
      education, crime and the physical environment) were assessed by sex, age,
      educational and ethnic group. RESULTS: Small overall improvements were seen on
      all domains in NDC areas but similar improvements were also seen in comparator
      areas. In NDC areas, higher educational groups were more likely to stop smoking,
      less likely to develop a limiting long-term illness, more likely to find
      employment and more likely to participate in education or training (p for trend
      <0.05). Older people and women were less likely to find employment and
      experienced smaller increases in income. These patterns were generally mirrored
      in comparator areas, although the education gradient in participation in
      education or training was less steep in NDC areas. CONCLUSIONS: Evidence from two
      year follow-up does not support an NDC effect, either overall or for particular
      population groups. Residents with lower education experienced the least
      favourable health profiles at baseline and the smallest improvements. Programme
      leaders should consider how to encourage participation among those with the
      lowest education. A shallower social gradient in participation in education and
      training in NDC areas and a lack of gradient in income, crime and environmental
      outcomes indicate that some aspects of the programme may be reaching all sections
      of the community.

PMID- 18339822
TI  - Correlates of hepatitis C virus seropositivity in prison inmates: a meta
      analysis.
AB  - BACKGROUND: The prevalence of infection with hepatitis C virus (HCV) is higher
      among prison inmates compared with the general population because of the high
      proportion of injecting drug users (IDU). METHODS: A meta-analysis of studies on
      HCV infection in the correctional system was performed. The main objective was to
      analyse risk factors for HCV infection and to assess HCV seroprevalence and
      incidence in prison. RESULTS: Thirty studies were included in the meta-analysis
      on HCV prevalence. IDU were approximately 24 times more likely than non-IDU to be
      HCV positive. The odds ratio of being HCV positive was three times higher for
      inmates exposed to tattooing than those not exposed. The odds ratio among women
      was 1.44 compared with men. CONCLUSIONS: The differences in HCV seroprevalence
      among studies can largely be explained by differences in the proportion of
      inmates who are IDU and partly by differences in seroprevalence among IDU in the
      community. Tattooing and female gender were also associated with HCV positivity.
      These findings should be taken into account when planning prevention activities
      in prisons.

PMID- 18339823
TI  - Using national health weeks to deliver deworming to children: lessons from
      Mexico.
AB  - Mexico established national health weeks (NHWs) in the early 1980s to promote
      childhood vaccinations. Because of the cumulative worldwide peer-reviewed
      scientific evidence, the recommendations of the World Health Organization and
      other international organisations, the political will of the Mexican government
      and the infrastructure provided by the NHWs, deworming was added to the NHWs in
      1993. In addition to the Ministry of Health, several other government
      organisations participated in administering the deworming component. Tens of
      millions of school-age and preschool children between the ages of 2 years and 14
      years now receive deworming (a single 400 mg dose of albendazole) approximately
      every 8 months. Between 1993 and 1998 evaluations were carried out in over 90,000
      children to determine the effect of NHWs on the prevalence of geohelminth
      infections. In 1993, the overall prevalence of Ascaris was 20% and that of
      Trichuris was 15%. Prevalences decreased significantly over time (p <0.001).
      Treatment efficacy for Ascaris ranged from 91.6% to 85.3%, and for Trichuris,
      from 97.9% to 42.6%. In 1998, after conducting 12 NHWs with deworming, the
      respective prevalences were Ascaris 8% and Trichuris 11%. The experience of
      Mexico in integrating albendazole into its NHWs shows how deworming can be
      delivered to large numbers of at-risk children using an existing infrastructure.
      The NHW approach may be generalisable in other countries with successful national
      vaccination campaigns. The challenge remaining is to sustain the deworming
      programme until other longer-term behavioural, environmental and socioeconomic
      changes can be implemented.

PMID- 18339824
TI  - Meaningful differences in maternal smoking behaviour during pregnancy:
      implications for infant behavioural vulnerability.
AB  - BACKGROUND: Smoking during pregnancy has been consistently associated with risk
      of problem behaviour in offspring. There is debate about whether this association
      reflects a teratological effect or is a marker for problematic maternal
      characteristics. We test these "competing" hypotheses by examining whether (1)
      exposure is associated with an early risk pathway by testing its association with
      infant temperamental difficultness, and (2) whether pregnancy quitting is
      associated with an early protective pathway, testing its association with easy
      infant temperament. METHODS: We used the 9-month-old sweep of the Millennium
      Cohort Study, a cohort of over 18,000 infants born in 2000-2. Mothers were
      classified as pregnancy non-smokers, quitters and light or heavy smokers.
      Temperamental positive mood, receptivity to novelty and regularity were assessed
      with the Carey Infant Temperament Scale. RESULTS: Pregnancy quitters had infants
      with the highest scores of easy temperament and heavy smokers had infants with
      the lowest scores (F = 28.51, p<0.001). Pregnancy smoking also predicted
      difficult temperament: heavy smoking was associated with increased risk of low
      positive mood (OR = 1.17, p = 0.09). In contrast, pregnancy quitting exerted a
      protective effect with decreased risk of distress to novelty (OR = 0.79, p<0.01)
      and irregularity (OR = 0.89, p = 0.02) in these infants. CONCLUSIONS: Pathways
      from pregnancy smoking to offspring behaviour are complex and multi-determined.
      These findings suggest that both exposure and maternal characteristics associated
      with pregnancy smoking status contribute to offspring behavioural patterns.
      Research that characterises differences between quitters and persistent smokers
      and examines the role of these differences in prediction of early vulnerabilities
      and problems in adaptation over time will be important for elucidating these
      pathways.

PMID- 18339825
TI  - Social inequality in fetal growth: a comparative study of Denmark, Finland,
      Norway and Sweden in the period 1981-2000.
AB  - OBJECTIVE: To examine the socioeconomic patterns and time trends in fetal growth
      in Denmark, Finland, Norway, and Sweden from 1981 to 2000. DESIGN AND SETTINGS:
      Data on all live-born singleton births was drawn from national population
      registries in each of the four countries (Denmark n = 1,077,584; Finland n =
      400,442; Norway n = 929,458; Sweden n = 1,761,562). MAIN OUTCOME MEASURE: Slope
      index of inequality (SII) and mean differences in birthweight for gestational
      age, SII and risk differences in small-for-gestational-age (SGA) and large-for
      gestational-age (LGA) infants. RESULTS: In all countries, gradients in fetal
      growth by parental education existed. Low parental education was associated with
      lower birthweight, increased risk of SGA and decreased risk of LGA. Mother's
      education exerted the strongest influence on outcomes, whereas father's education
      had a weaker effect. The educational gradients as measured by the SII were
      generally steepest in Denmark, followed by Norway, Sweden, and Finland. From 1981
      to 2000, the educational gradients in birthweight decreased in all countries,
      except Denmark where it increased. All countries experienced small decreases in
      the educational gradient in SGA over time. CONCLUSION: The economic recession in
      Denmark in the 1980s was concurrent with an increase in disparities in fetal
      growth, whereas the economic recession in Finland and Sweden in the early 1990s
      did not substantially increase the socioeconomic inequality in fetal growth. The
      economic growth in the later part of the 1990s may have diminished the
      socioeconomic inequality in fetal growth in Finland, Norway, and Sweden.

PMID- 18339826
TI  - Job loss from poor health, smoking and obesity: a national prospective survey in
      France.
AB  - BACKGROUND AND OBJECTIVES: Health selection into unemployment may be either
      direct or operate by reference to health-related behaviours rather than health
      per se (indirect selection). Panel data are desirable to investigate selection
      effects, and the two types of selection processes may be concurrent. We examine
      jointly the roles of health and health-related behaviours as precursors of
      unemployment, in order to disentangle direct from indirect selection processes.
      DESIGN: The data of a multi-round nationally representative health survey in
      France were analysed longitudinally, based on three data collection rounds: 1992
      5, 1996-8 and 2000-2. Following employees salaried in the private sector and aged
      30-54 years at baseline, we explored through logistic regression the influence of
      non-optimal self-rated health, smoking and obesity on the risk of being found
      unemployed 4 years later. RESULTS: After adjustment for self-rated health,
      obesity was found to be a significant precursor of unemployment in women, and
      heavy smoking had that role in men. After adjustment for smoking and obesity,
      poor health at baseline was found to be a significant precursor of unemployment
      in both genders. CONCLUSION: Those findings confirm the intrinsic role of poor
      health and of health-related behaviours as precursors of unemployment, with
      gender-specific patterns for the latter. Public policy prescriptions regarding
      employees' protection from job insecurities should integrate appropriate
      accommodations of health limitations, and the personal factors underlying
      unfavourable work and health behaviours should be investigated, in order to
      thwart indirect selection phenomena.

PMID- 18339827
TI  - When does work stress hurt? Testing the interaction with socioeconomic position
      in the Heinz Nixdorf Recall Study.
AB  - STUDY OBJECTIVE: To study systematically the separate and combined effects of
      work stress and socioeconomic position on three measures of health in an
      unselected working population. DESIGN: Two exposures (high demand/low control
      ("job strain"); effort-reward imbalance at work) are related to angina pectoris,
      depression, and poor self-rated health in a cross-sectional study design in which
      socioeconomic position was measured by occupational position and educational
      level. SETTING: Baseline data of a prospective population-based cohort study in
      Germany, collected between 2000 and 2003. PARTICIPANTS: 1749 employed or self
      employed men and women (36.3% of total sample) aged 45-65 years. MAIN RESULTS:
      Effort-reward imbalance and job strain were associated with elevated odds ratios
      of all three health measures, using logistic regression analysis. The prevalence
      of poorer health was always highest in subgroups defined by high work stress and
      low socioeconomic position, with respective odds ratios ranging from 2.30 to 2.98
      (95% CI 1.38 to 4.52) for self-rated health, 1.70 to 2.24 (95% CI 1.04 to 3.88)
      for angina and 2.61 to 8.20 (95% CI 1.53 to 14.15) for depression. CONCLUSION:
      Although stress at work was related to poorer health in the total study group,
      the strongest associations were consistently observed in men and women with low
      educational level or low occupational position. Worksite health promotion should
      be directed primarily towards these target groups.

PMID- 18339828
TI  - Physical activity in older women: associations with area deprivation and with
      socioeconomic position over the life course: observations in the British Women's
      Heart and Health Study.
AB  - OBJECTIVE: To assess the association between residential area-level deprivation,
      individual life-course socioeconomic position and adult levels of physical
      activity in older British women. METHODS: A cross-sectional study of 4286 British
      women aged 60-79 years at baseline, who were randomly selected from general
      practitioner lists in 23 British towns between April 1999 and March 2001 (the
      British Women's Heart and Health Study). RESULTS: All three of childhood
      socioeconomic position, adult socioeconomic position and area of residence (in
      adulthood) deprivation were independently (of each other and potential
      confounders) associated with physical activity. There was a cumulative effect of
      life-course socioeconomic position on physical activity, with the proportion who
      undertook no moderate or vigorous activity per week increasing linearly with each
      additional indicator of life-course socioeconomic position (p<0.001 for linear
      trend). CONCLUSION: Adverse socioeconomic position across the life-course is
      associated with an increased cumulative risk of low physical activity in older
      women. Reducing socioeconomic inequalities across the life course would thus be
      expected to improve levels of physical activity and the associated health
      benefits in later life.

PMID- 18339829
TI  - Childhood socioeconomic circumstances and adult height and leg length in central
      and eastern Europe.
AB  - BACKGROUND: Adult height and leg length have been shown to be positively
      associated with childhood socioeconomic circumstances in several studies in
      western populations. This study will determine whether similar associations are
      observable in settings with different social histories, and will assess whether
      adult leg length is more strongly associated than adult height. METHODS: Random
      samples of men and women aged 45-69 years were taken from population registers in
      Novosibirsk (Russia), Krakow (Poland) and six towns of the Czech Republic,
      recruiting nearly 29,000 people. Participants completed a questionnaire that
      included questions regarding their mother's and father's education (not available
      in the Czech Republic) and ownership of several household items when they were 10
      years old. Participants' standing and sitting heights were measured and from
      these an estimate of leg length was derived. Associations between indicators of
      childhood socioeconomic circumstances and anthropometric measures were analysed
      using linear regression. RESULTS: Russian individuals were shorter and reported
      fewer household assets at the age of 10 years than Czech and Polish individuals.
      Parental education and household assets were strongly associated with each other
      and both were independently associated with height, leg length and trunk length.
      Height was associated with childhood circumstances more strongly than leg length.
      The associations of childhood circumstances with the leg/trunk ratio were weak
      and inconsistent. CONCLUSION: In these urban populations in eastern Europe, adult
      height is associated with childhood conditions at least as strongly as leg
      length.

PMID- 18339830
TI  - Perineal use of talc and risk of ovarian cancer.
AB  - Ovarian cancer is one of the most common gynaecological neoplasms, especially in
      industrialised countries. The aetiology of the disease is not well understood,
      except that inherited mutations in the breast cancer genes BRCA-1 and BRCA-2
      account for up to 10% of all cases, and child-bearing, oral contraceptive use and
      breast-feeding reduce the risk. Some environmental exposures, notably talc and
      asbestos, have been suspected as ovarian carcinogens.

PMID- 18339831
TI  - Cost effectiveness of the Expert Patients Programme (EPP) for patients with
      chronic conditions.
AB  - OBJECTIVE: To assess the cost effectiveness of the Expert Patients Programme
      (EPP) intervention compared to a treatment as usual alternative. DESIGN: Two-arm
      pragmatic randomised controlled trial design with waiting list control. SETTING:
      Community settings in England. PATIENTS: Patients with a wide range of self
      defined long-term conditions. INTERVENTION: The EPP based on the US chronic
      disease self management program (CDSMP), a lay-led self-care group involving six
      weekly sessions to teach self-care support skills. MAIN OUTCOME MEASURES: Costs
      estimated over a 6-month period from a societal perspective. Health outcomes
      estimated in terms of quality adjusted life years (QALYs) generated by patients'
      response to the EQ5D at baseline and 6-month follow-up. RESULTS: The intervention
      group is associated with better patient outcomes, at slightly lower cost.
      Specifically, the intervention group has a 0.020 QALY gain compared with the
      control group, and a reduced cost of around 27 pounds per patient. The
      intervention would therefore be considered dominant. While the QALYs gained are
      small in absolute terms, an additional 0.02 QALY is equivalent to an extra one
      week of perfect health per year. When the value of a QALY is 20,000 pounds the
      EPP has a probability of 94% of being cost effective. Indeed, for all plausible
      values of willingness-to-pay for a QALY the EPP group is more likely to be cost
      effective than the control group. CONCLUSIONS: The EPP intervention evaluated in
      this trial is very likely to provide a cost effective alternative to usual care
      in people with long-term conditions.

PMID- 18339832
TI  - Measuring the health effects of gender.
AB  - The health effects of gender are mediated via group-level constraints of sex
      roles and norms, discrimination and marginalisation of individuals, and
      internalisation of the stresses of role discordance. Although gender is
      frequently a lens through which data are interpreted there are few composite
      measures that insert gender as an independent variable into research design.
      Instead, sex disaggregation of data is often conflated with gender, identifying
      statistically significant but sometimes clinically insignificant sex differences.
      To directly assess the impact of gender on wellbeing requires development of
      group and individual-level derived variables. At the ecological level such a
      summative variable could be composed of a selection of group-level measures of
      equality between sexes. This gender index could be used in ecological and
      individual-level studies of health outcomes. A quantitative indicator of gender
      role acceptance and of the personal effects of gender inequities could insert the
      often hidden variable of gender into individual-level clinical research.

PMID- 18339833
TI  - Job strain and ischaemic disease: does the inclusion of older employees in the
      cohort dilute the association? The WOLF Stockholm Study.
AB  - OBJECTIVE: Evidence on the association between job strain and ischaemic disease
      is mixed. This study examined whether including older age individuals in a cohort
      used to assess job strain attenuates findings towards the null. DESIGN: A
      prospective cohort study with baseline screening in 1992-5. A follow-up for
      ischaemic disease until 2003 was based on linkages to national registries.
      Ischaemic disease was corroborated by objective criteria (hospitalisation as a
      result of acute myocardial infarction, unstable angina or ischaemic stroke; or
      death from ischaemic heart disease, cardiac arrest or ischaemic stroke).
      PARTICIPANTS: 3160 male employees aged 19-65 years without pre-existing or
      current ischaemic disease. RESULTS: 93 cases of incident ischaemic disease were
      recorded. In the 19-55 year age group, the participants with job strain had a
      1.76 (95% CI 1.05 to 2.95) times higher age-adjusted risk of incident ischaemic
      disease than those free of strain. Further adjustment for conventional
      cardiovascular risk factors had little effect on this association, but the impact
      of job strain was reduced by 70% to non-significant after the inclusion of
      employees older than 55 years in the cohort (hazard ratio 1.22, 95% CI 0.75 to
      1.96). CONCLUSIONS: Including older employees in a cohort may dilute the effect
      of job strain on cardiovascular disease and is a potential reason for
      inconsistent findings in previous studies.

PMID- 18339837
TI  - Eag1: an emerging oncological target.
AB  - Emerging evidence indicates that ion channels act in a variety of physiologic and
      pathologic processes beyond electronic signal transmission, including in cancer.
      We recently found that the potassium channel Eag1 can mediate cancer progression
      and that a monoclonal antibody, which inhibits Eag1 action, can effectively
      restrict cancer cell proliferation. We discuss how Eag1 targeting may be useful
      in diagnostic or therapeutic settings.

PMID- 18339838
TI  - Tumor-specific T-cell memory: clearing the regulatory T-cell hurdle.
AB  - Antitumor immune responses can be stimulated by interfering with regulatory T
      cell (T(reg)) function. However, this effect is short lived unless T-cell memory
      to tumor antigens can be generated. Our recent studies show that T(reg) cells not
      only limit primary responses to tumor/self-antigens in tumor-bearing hosts but
      also prevent the natural generation of T-cell memory to such antigens. Here, we
      discuss the role of T(reg) cells in suppressing T-cell memory after surgical
      excision of tumors and the potential clinical benefits of overcoming this
      suppression.

PMID- 18339839
TI  - Rictor and integrin-linked kinase interact and regulate Akt phosphorylation and
      cancer cell survival.
AB  - An unbiased proteomic screen to identify integrin-linked kinase (ILK) interactors
      revealed rictor as an ILK-binding protein. This finding was interesting because
      rictor, originally identified as a regulator of cytoskeletal dynamics, is also a
      component of mammalian target of rapamycin complex 2 (mTORC2), a complex
      implicated in Akt phosphorylation. These functions overlap with known ILK
      functions. Coimmunoprecipitation analyses confirmed this interaction, and ILK and
      rictor colocalized in membrane ruffles and leading edges of cancer cells. Yeast
      two-hybrid assays showed a direct interaction between the NH(2)- and COOH
      terminal domains of rictor and the ILK kinase domain. Depletion of ILK and rictor
      in breast and prostate cancer cell lines resulted in inhibition of Akt Ser(473)
      phosphorylation and induction of apoptosis, whereas, in several cell lines,
      depletion of mTOR increased Akt phosphorylation. Akt and Ser(473)P-Akt were
      detected in ILK immunoprecipitates and small interfering RNA-mediated depletion
      of rictor, but not mTOR, inhibited the amount of Ser(473)P-Akt in the ILK
      complex. Expression of the NH(2)-terminal (1-398 amino acids) rictor domain also
      resulted in the inhibition of ILK-associated Akt Ser(473) phosphorylation. These
      data show that rictor regulates the ability of ILK to promote Akt phosphorylation
      and cancer cell survival.

PMID- 18339840
TI  - SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer
      invasion.
AB  - SOX9 is a transcription factor that plays a critical role in the development of
      multiple tissues. We previously reported that SOX9 in normal human adult prostate
      was restricted to basal epithelium. SOX9 was also expressed in a subset of
      prostate cancer (PCa) cells and was increased in relapsed hormone-refractory PCa.
      Moreover, SOX9 expression in PCa cell lines enhanced tumor cell proliferation and
      was beta-catenin regulated. Here we report additional in vivo results showing
      that SOX9 is highly expressed during fetal prostate development by epithelial
      cells expanding into the mesenchyme, suggesting it may contribute to invasive
      growth in PCa. Indeed, SOX9 overexpression in LNCaP PCa xenografts enhanced
      growth, angiogenesis, and invasion. Conversely, short hairpin RNA-mediated SOX9
      suppression inhibited the growth of CWR22Rv1 PCa xenografts. These results
      support important functions of SOX9 in both the development and maintenance of
      normal prostate, and indicate that these functions contribute to PCa tumor growth
      and invasion.

PMID- 18339841
TI  - Novel SN-38-incorporated polymeric micelle, NK012, strongly suppresses renal
      cancer progression.
AB  - It has been recently reported that NK012, a 7-ethyl-10-hydroxy-camptothecin (SN
      38)-releasing nanodevice, markedly enhances the antitumor activity of SN-38,
      especially in hypervascular tumors through the enhanced permeability and
      retention effect. Renal cell carcinoma (RCC) is a typical hypervascular tumor
      with an irregular vascular architecture. We therefore investigated the antitumor
      activity of NK012 in a hypervascular tumor model from RCC. Immunohistochemical
      examination revealed that Renca tumors contained much more CD34-positive
      neovessels than SKRC-49 tumors. Compared with CPT-11, NK012 had significant
      antitumor activity against both bulky Renca and SKRC-49 tumors. Notably, NK012
      eradicated rapid-growing Renca tumors in 6 of 10 mice, whereas it failed to
      eradicate SKRC-49 tumors. In the pulmonary metastasis treatment model, an
      enhanced and prolonged distribution of free SN-38 was observed in metastatic lung
      tissues but not in nonmetastatic lung tissues after NK012 administration. NK012
      treatment resulted in a significant decrease in metastatic nodule number and was
      of benefit to survival. Our study shows the outstanding advantage of polymeric
      micelle-based drug carriers and suggests that NK012 would be effective in
      treating disseminated RCCs with irregular vascular architectures.

PMID- 18339842
TI  - Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc.
AB  - Neoplastic lesions typically express specific carbohydrate antigens on
      glycolipids, mucins, and other glycoproteins. Such antigens are often under
      epigenetic control and are subject to reversion and loss upon therapeutic
      selective pressure. We report here that two of the most common tumor-associated
      carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in
      the gene Cosmc that encodes a molecular chaperone required for formation of the
      active T-synthase. Diverse neoplastic lesions, including colon cancer and
      melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of
      function mutations in Cosmc. In addition, two human cervical cancer specimens
      that showed expression of the Tn/STn antigens were also found to have mutations
      in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the
      first example of somatic mutations in multiple types of cancers that cause global
      alterations in cell surface carbohydrate antigen expression.

PMID- 18339843
TI  - Roles of achaete-scute homologue 1 in DKK1 and E-cadherin repression and
      neuroendocrine differentiation in lung cancer.
AB  - The proneural basic-helix-loop-helix protein achaete-scute homologue 1 (ASH1) is
      expressed in a very limited spectrum of normal and cancerous cells in a lineage
      specific manner, including normal pulmonary neuroendocrine cells and lung cancer
      cells with neuroendocrine features. Our previous results indicated that ASH1 may
      play a crucial role in the growth and survival of lung cancers with
      neuroendocrine features, which prompted us to investigate the molecular function
      of ASH1 in relation to its involvement in carcinogenic processes. Herein, we
      report for the first time that ASH1 functions as a dual transcription factor by
      activating neuroendocrine differentiation markers and also repressing putative
      tumor suppressors. This protein was found to inactivate DKK1 and DKK3, negative
      regulators of Wnt/beta-catenin signaling, E-cadherin, and integrin beta1 through
      ASH1-mediated deacetylation and repressive trimethylation of lysine 27 (H3K27me3)
      of histone H3 in the promoter regions of DKK1 and E-cadherin. In addition, ASH1
      transduced A549 adenocarcinoma cells exhibited markedly altered morphology
      characteristics compared with lung cancer cells with neuroendocrine features both
      in vitro and in vivo and also grew faster in vivo. Our results provide important
      clues for a better understanding of the molecular and cellular biological roles
      of ASH1 in the process of carcinogenesis of lung cancers with neuroendocrine
      features and warrant future investigations to shed light on the lineage-specific
      dependency of this transcription factor with dual functions.

PMID- 18339844
TI  - Cancer-associated transforming growth factor beta type II receptor gene mutant
      causes activation of bone morphogenic protein-Smads and invasive phenotype.
AB  - Transforming growth factor beta (TGFbeta) plays a key role in maintaining tissue
      homeostasis by inducing cell cycle arrest, differentiation and apoptosis, and
      ensuring genomic integrity. Furthermore, TGFbeta orchestrates the response to
      tissue injury and mediates repair by inducing epithelial to mesenchymal
      transition and by stimulating cell motility and invasiveness. Although loss of
      the homeostatic activity of TGFbeta occurs early on in tumor development, many
      advanced cancers have coopted the tissue repair function to enhance their
      metastatic phenotype. How these two functions of TGFbeta become uncoupled during
      cancer development remains poorly understood. Here, we show that, in human
      keratinocytes, TGFbeta induces phosphorylation of Smad2 and Smad3 as well as
      Smad1 and Smad5 and that both pathways are dependent on the kinase activities of
      the type I and II TGFbeta receptors (T beta R). Moreover, cancer-associated
      missense mutations of the T beta RII gene (TGFBR2) are associated with at least
      two different phenotypes. One type of mutant (TGFBR2(E526Q)) is associated with
      loss of kinase activity and all signaling functions. In contrast, a second mutant
      (TGFBR2(R537P)) is associated with high intrinsic kinase activity, loss of
      Smad2/3 activation, and constitutive activation of Smad1/5. Furthermore, this
      TGFBR2 mutant endows the carcinoma cells with a highly motile and invasive
      fibroblastoid phenotype. This activated phenotype is T beta RI (Alk-5)
      independent and can be reversed by the action of a dual T beta RI and T beta RII
      kinase inhibitor. Thus, identification of such activated T beta RII receptor
      mutations in tumors may have direct implications for appropriately targeting
      these cancers with selective therapeutic agents.

PMID- 18339845
TI  - BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in
      breast cancer.
AB  - Screening for tumor suppressor genes in breast cancer revealed multiple
      truncating mutations of PB1, which encodes the BAF180 subunit of the PBAF
      chromatin remodeling complex. Mutation was associated with loss of heterozygosity
      of the wild-type allele. BAF180 complementation of BAF180-mutant tumor cells
      caused G(1) arrest that was dependent on increased expression of the
      cyclin/cyclin-dependent kinase inhibitor p21/WAF1/CIP1. Endogenous wild-type
      BAF180 bound to the p21 promoter and was required for proper p21 expression and
      G(1) arrest after transforming growth factor-beta and gamma-radiation treatment.
      BAF180 thus functions on two tumor suppressor signaling pathways as a physiologic
      mediator of p21 expression. We conclude that BAF180 suppresses tumorigenesis, at
      least in part, through its ability to regulate p21.

PMID- 18339846
TI  - Prediction of cancer driver mutations in protein kinases.
AB  - A large number of somatic mutations accumulate during the process of
      tumorigenesis. A subset of these mutations contribute to tumor progression (known
      as "driver" mutations) whereas the majority of these mutations are effectively
      neutral (known as "passenger" mutations). The ability to differentiate between
      drivers and passengers will be critical to the success of upcoming large-scale
      cancer DNA resequencing projects. Here we show a method capable of discriminating
      between drivers and passengers in the most frequently cancer-associated protein
      family, protein kinases. We apply this method to multiple cancer data sets,
      validating its accuracy by showing that it is capable of identifying known
      drivers, has excellent agreement with previous statistical estimates of the
      frequency of drivers, and provides strong evidence that predicted drivers are
      under positive selection by various sequence and structural analyses.
      Furthermore, we identify particular positions in protein kinases that seem to
      play a role in oncogenesis. Finally, we provide a ranked list of candidate driver
      mutations.

PMID- 18339847
TI  - Bin3 deletion causes cataracts and increased susceptibility to lymphoma during
      aging.
AB  - Bin3 encodes an evolutionarily conserved and ubiquitously expressed member of the
      BAR superfamily of curved membrane and GTPase-binding proteins, which includes
      the BAR, PCH/F-BAR, and I-BAR adapter proteins implicated in signal transduction
      and vesicular trafficking. In humans, Bin3 maps to chromosome 8p21.3, a region
      widely implicated in cancer suppression that is often deleted in non-Hodgkin's
      lymphomas and various epithelial tumors. Yeast studies have suggested roles for
      this gene in filamentous actin (F-actin) organization and cell division but its
      physiologic functions in mammals have not been investigated. Here we report that
      homozygous inactivation of Bin3 in the mouse causes cataracts and an increased
      susceptibility to lymphomas during aging. The cataract phenotype was marked by
      multiple morphologic defects in lens fibers, including the development of
      vacuoles in cortical fibers and a near total loss of F-actin in lens fiber cells
      but not epithelial cells. Through 1 year of age, no other phenotypes were
      apparent; however, by 18 months of age, Bin3(-/-) mice exhibited a significantly
      increased incidence of lymphoma. Bin3 loss did not affect normal cell
      proliferation, F-actin organization, or susceptibility to oncogenic
      transformation. In contrast, it increased the proliferation and invasive motility
      of cells transformed by SV40 large T antigen plus activated ras. Our findings
      establish functions for Bin3 in lens development and cancer suppression during
      aging. Further, they define Bin3 as a candidate for an unidentified tumor
      suppressor that exists at the human chromosome 8p21.3 locus.

PMID- 18339848
TI  - EphA2 is an essential mediator of UV radiation-induced apoptosis.
AB  - One of the physiologic consequences of excessive UV radiation (UVR) exposure is
      apoptosis. This critical response serves to eliminate genetically injured cells
      and arises, in part, from activation of DNA damage and p53 signaling. Other
      contributory pathways, however, likely exist but have not been fully
      characterized. In a recent global screen of UVR response genes in melanocytes, we
      identified the receptor tyrosine kinase EPHA2. Using a combination of genetic and
      pharmacologic approaches, we set out to investigate the upstream regulation of
      EphA2 by UVR and the functional consequences of this effect. We found that the
      UVR-associated increase in EphA2 occurs in melanocytes, keratinocytes, and
      fibroblasts from both human and murine sources. More specifically, UVR
      effectively up-regulated EphA2 individually in p53-null, p63-null, and p73-null
      murine embryonic fibroblasts (MEF), suggesting that the p53 family of
      transcription factors is not essential for the observed effect. However,
      inhibition of mitogen-activated protein kinase (MAPK) signaling by U0126 and
      PD98059 significantly reduced the UVR response whereas overexpression of
      oncogenic NRAS led to an increase in EphA2. These results confirm that UVR
      induces EphA2 by a p53-independent, but MAPK-dependent, mechanism. In response to
      UV irradiation, Epha2(-/-) MEFs were highly resistant to UVR-mediated
      cytotoxicity and apoptosis whereas introduction of EphA2 into both wild-type and
      p53-null MEFs led to activation of an apoptotic program that can be blocked by
      caspase-8 inhibition. These functional findings suggest that EphA2 is in fact an
      essential p53-independent, caspase-8-dependent proapoptotic factor induced by
      UVR.

PMID- 18339849
TI  - Thyroid hormone receptors suppress pituitary tumor transforming gene 1 activity
      in hepatoma.
AB  - Pituitary tumor transforming gene 1 (PTTG1) is expressed in most tumors. However,
      whether thyroid hormone (T(3)) and its receptors (TR) regulate PTTG1 in human
      hepatocellular carcinomas (HCC) remains unclear. Previous cDNA microarrays
      revealed PTTG1 is down-regulated by T(3)/TR. This study investigated the
      significance of PTTG1 regulation by T(3) in HCC cells. The PTTG1 mRNA and protein
      expression were repressed by T(3) in HCC cell lines overexpressing TR. However,
      after knockdown of TRs expression by RNA interference, PTTG1 repression by T(3)
      was abolished. Similar results were observed in thyroidectomized rats. To
      localize the regulatory region in the PTTG1 promoter, serial deletions within the
      PTTG1 promoter region were constructed. The promoter activity of the PTTG1 gene
      was repressed (25-51%) by T(3). Additionally, these findings indicate that PTTG1
      may be regulated by Sp1. The critical role of the -594 and -520 Sp1 binding sites
      was confirmed by electrophoretic mobility shift assay. Transfection with Sp1
      expression vector enhanced the activity of the PTTG1 promoter fragment reporter.
      Also, Sp1 was down-regulated in HCC cells and in thyroidectomized rat after T(3)
      treatment. Additionally, ectopic expression of PTTG1 promotes cell proliferation
      in Hep3B hepatoma cells. Conversely, knockdown of PTTG1 or Sp1 expression reduced
      cell proliferation in HepG2 cells. Notably, the expression of PTTG1 and Sp1 was
      inversely correlated with the expression of TR proteins in HCC. Together, these
      findings indicate that PTTG1 gene expression is mediated by Sp1 and is indirectly
      down-regulated by T(3). Finally, overexpression of PTTG1 or SP1 in HCCs is TR
      dependent and crucial in the development of HCC.

PMID- 18339850
TI  - Promoter methylation of genes in and around the candidate lung cancer
      susceptibility locus 6q23-25.
AB  - Chromosomal aberrations associated with lung cancer are frequently observed in
      the long arm of chromosome 6. A candidate susceptibility locus at 6q23-25 for
      lung cancer was recently identified; however, no tumor suppressor genes
      inactivated by mutation have been identified in this locus. Genetic, epigenetic,
      gene expression, and in silico screening approaches were used to select 43 genes
      located in 6q12-27 for characterization of methylation status. Twelve (28%) genes
      were methylated in at least one lung cancer cell line, and methylation of 8 genes
      was specific to lung cancer cell lines. Five of the 8 genes with the highest
      prevalence for methylation in cell lines (TCF21, SYNE1, AKAP12, IL20RA, and
      ACAT2) were examined in primary lung adenocarcinoma samples from smokers (n =
      100) and never smokers (n = 75). The prevalence for methylation of these genes
      was 81%, 50%, 39%, 26%, and 14%, respectively, and did not differ by smoking
      status or age at diagnosis. Transcription of SYNE1, AKAP12, and IL20RA was
      completely silenced by hypermethylation and could be restored after treatment
      with 5-aza-2-deoxycytidine. Significant associations were found between
      methylation of SYNE1 and TCF21, SYNE1 and AKAP12, and AKAP12 and IL20RA,
      indicating a coordinated inactivation of these genes in tumors. A higher
      prevalence for methylation of these genes was not associated with early-onset
      lung cancer cases, most likely precluding their involvement in familial
      susceptibility to this disease. Together, our results indicate that frequent
      inactivation of multiple candidate tumor suppressor genes within chromosome 6q
      likely contributes to development of sporadic lung cancer.

PMID- 18339851
TI  - CX3CR1 is expressed by prostate epithelial cells and androgens regulate the
      levels of CX3CL1/fractalkine in the bone marrow: potential role in prostate
      cancer bone tropism.
AB  - We have previously shown that the chemokine fractalkine promotes the adhesion of
      human prostate cancer cells to bone marrow endothelial cells as well as their
      migration toward human osteoblasts in vitro. Thus, the interaction of fractalkine
      with its receptor CX3CR1 could play a crucial role in vivo by directing
      circulating prostate cancer cells to the bone. We found that although CX3CR1 is
      minimally detectable in epithelial cells of normal prostate glands, it is
      overexpressed upon malignant transformation. Interestingly, osteoblasts, stromal
      and mesenchymal cells derived from human bone marrow aspirates express the cell
      bound form of fractalkine, whereas the soluble form of the chemokine is detected
      in bone marrow supernatants. To investigate the mechanisms regulating the levels
      of soluble fractalkine in the bone marrow, we focused on androgens, which play a
      critical role in both prostate cancer progression and skeletal metastasis. Here,
      we show that dihydrotestosterone dramatically increases the cleavage of
      fractalkine from the plasma membrane of bone cells and its action is reversed by
      nilutamide--an antagonist of the androgen receptor--as well as the wide-spectrum
      inhibitor of matrix metalloproteases, GM6001. However, dihydrotestosterone was
      unable to induce fractalkine-cleavage from human bone marrow endothelial cells.
      Thus, androgens could promote the extravasation of CX3CR1-bearing cancer cells on
      a fractalkine concentration gradient, while leaving unaltered their ability to
      adhere to the bone marrow endothelium. In conclusion, our results indicate that
      CX3CR1, fractalkine, and the enzymes responsible for its cleavage might represent
      suitable targets for therapies aiming to counteract skeletal secondary tumors
      from prostate adenocarcinoma.

PMID- 18339852
TI  - PTEN has tumor-promoting properties in the setting of gain-of-function p53
      mutations.
AB  - We show, for the first time, that the tumor suppressor PTEN can have tumor
      promoting properties. We show that PTEN acquires these unexpected properties by
      enhancing gain-of-function mutant p53 (mut-p53) protein levels. We find that PTEN
      restoration to cells harboring mut-p53 leads to induction of G(1)-S cell cycle
      progression and cell proliferation and to inhibition of cell death. Conversely,
      PTEN inhibition in cells expressing wild-type PTEN and mut-p53 leads to
      inhibition of cell proliferation and inhibition of in vivo tumor growth. We show
      the dependency of the tumor-promoting effects of PTEN on mut-p53 by showing that
      knockdown of mut-p53 expression inhibits or reverses the tumor-promoting effects
      of PTEN. Mechanistically, we show that PTEN expression enhances mut-p53 protein
      levels via inhibition of mut-p53 degradation by Mdm2 and possibly also via direct
      protein binding. These findings describe a novel function of PTEN and have
      important implications for experimental and therapeutic strategies that aim at
      manipulating PTEN or p53 in human tumors. They suggest that the mutational status
      of PTEN and p53 should be considered to achieve favorable therapeutic outcomes.
      The findings also provide an explanation for the low frequency of simultaneous
      mutations of PTEN and p53 in human cancer.

PMID- 18339853
TI  - Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2
      synthesis in colon cancer cells.
AB  - Lipid bodies (lipid droplets) are emerging as dynamic organelles involved in
      lipid metabolism and inflammation. Increased lipid body numbers have been
      described in tumor cells; however, its functional significance in cancer has
      never been addressed. Here, we showed increased number of lipid bodies in tumor
      tissues from patients with adenocarcinoma of colon submitted to surgical
      resection when compared with an adjacent normal tissue. Accordingly, increased
      numbers of lipid bodies were observed in human colon adenocarcinoma cell lines
      and in a H-rasV12-transformed intestinal epithelial cell line (IEC-6 H-rasV12)
      compared with nontransformed IEC-6 cells. The functions of lipid bodies in
      eicosanoid synthesis in cancer cells were investigated. CACO-2 cells have
      increased expression of cyclooxygenase-2 (COX-2) when compared with IEC-6 cells.
      We showed by immunolocalization that, in addition to perinuclear stain, COX-2 and
      prostaglandin E (PGE) synthase present punctate cytoplasmic localizations that
      were concordant with adipose differentiation-related protein-labeled lipid
      bodies. The colocalization of COX-2 at lipid bodies was confirmed by immunoblot
      of subcellular fractionated cells. Direct localization of PGE(2) at its synthesis
      locale showed that lipid bodies are sources of eicosanoids in the transformed
      colon cancer cells. Treatment with either aspirin or the fatty acid synthase
      inhibitor C75 significantly reduced the number of lipid bodies and PGE(2)
      production in CACO-2 and in IEC-6 H-rasV12 cells with effects in cell
      proliferation. Together, our results showed that lipid bodies in colon cancer
      cells are dynamic and functional active organelles centrally involved in PGE(2)
      synthesis and may potentially have implications in the pathogenesis of
      adenocarcinoma of colon.

PMID- 18339854
TI  - Rad6B is a positive regulator of beta-catenin stabilization.
AB  - Mutations in beta-catenin or other Wnt pathway components that cause beta-catenin
      accumulation occur rarely in breast cancer. However, there is some evidence of
      beta-catenin protein accumulation in a subset of breast tumors. We have recently
      shown that Rad6B, an ubiquitin-conjugating enzyme, is a transcriptional target of
      beta-catenin/TCF. Here, we show that forced Rad6B overexpression in MCF10A breast
      cells induces beta-catenin accumulation, which despite being ubiquitinated is
      stable and transcriptionally active. A similar relationship between Rad6B, beta
      catenin ubiquitination, and transcriptional activity was found in WS-15 and MDA
      MB-231 breast cancer cells, and mouse mammary tumor virus-Wnt-1 mammary tumor
      derived cells, implicating Rad6B in physiologic regulation of beta-catenin
      stability and activity. Ubiquitinated beta-catenin was detectable in chromatin
      immunoprecipitations performed with beta-catenin antibody in MDA-MB-231 but not
      MCF10A cells. Rad6B silencing caused suppression of beta-catenin
      monoubiquitination and polyubiquitination, and transcriptional activity. These
      effects were accompanied by a reduction in intracellular beta-catenin but with
      minimal effects on cell membrane-associated beta-catenin. Measurement of beta
      catenin protein stability by cycloheximide treatment showed that Rad6B silencing
      specifically decreases the stability of high molecular beta-catenin with minimal
      effect upon the 90-kDa nascent form. In vitro ubiquitination assays confirmed
      that Rad6B mediates beta-catenin polyubiquitination, and ubiquitin chain
      extensions involve lysine 63 residues that are insensitive to 26S proteasome.
      These findings, combined with our previous data that Rad6B is a transcriptional
      target of beta-catenin, reveal a positive regulatory feedback loop between Rad6B
      and beta-catenin and a novel mechanism of beta-catenin stabilization/activation
      in breast cancer cells.

PMID- 18339855
TI  - Kaposi's sarcoma-associated herpesvirus viral IFN regulatory factor 3 stabilizes
      hypoxia-inducible factor-1 alpha to induce vascular endothelial growth factor
      expression.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent associated
      with Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's
      disease. Hypoxia-inducible factor-1 (HIF-1) is the master regulator of both
      developmental and pathologic angiogenesis, composed of an oxygen-sensitive alpha
      subunit and a constitutively expressed beta-subunit. HIF-1 activity in tumors
      depends on the availability of the HIF-1 alpha subunit, the levels of which are
      increased under hypoxic conditions. Recent studies have shown that HIF-1 plays an
      important role in KSHV reactivation from latency and pathogenesis. Here, we
      report a novel mechanism by which KSHV activates HIF-1 activity. Specific
      interaction between KSHV viral IFN regulatory factor 3 (vIRF3) and the HIF-1
      alpha subunit led to the HIF-1 alpha stabilization and transcriptional
      activation, which induced vascular endothelial growth factor expression and
      ultimately facilitated endothelial tube formation. Remarkably, the central domain
      of vIRF3, containing double alpha-helix motifs, was sufficient not only for
      binding to HIF-1 alpha but also for blocking its degradation in normoxic
      conditions. This indicates that KSHV has developed a unique mechanism to enhance
      HIF-1 alpha protein stability and transcriptional activity by incorporating a
      viral homologue of cellular IRF gene into its genome, which may contribute to
      viral pathogenesis.

PMID- 18339856
TI  - 14-3-3 zeta down-regulates p53 in mammary epithelial cells and confers luminal
      filling.
AB  - Recent progress in diagnostic tools allows many breast cancers to be detected at
      an early preinvasive stage. Thus, a better understanding of the molecular basis
      of early breast cancer progression is essential. Previously, we discovered that
      14-3-3 zeta is overexpressed in >40% of advanced breast cancers, and this
      overexpression predicts poor patient survival. Here, we examined at what stage of
      breast disease 14-3-3 zeta overexpression occurs, and we found that increased
      expression of 14-3-3 zeta begins at atypical ductal hyperplasia, an early stage
      of breast disease. To determine whether 14-3-3 zeta overexpression is a decisive
      early event in breast cancer, we overexpressed 14-3-3 zeta in MCF10A cells and
      examined its effect in a three-dimensional culture model. We discovered that 14-3
      3 zeta overexpression severely disrupted the acini architecture resulting in
      luminal filling. Proper lumen formation is a result of anoikis, apoptosis due to
      detachment from the basement membrane. We found that 14-3-3 zeta overexpression
      conferred resistance to anoikis. Additionally, 14-3-3 zeta overexpression in
      MCF10A cells and in mammary epithelial cells (MEC) from 14-3-3 zeta transgenic
      mice reduced expression of p53, which is known to mediate anoikis.
      Mechanistically, 14-3-3 zeta induced hyperactivation of the phosphoinositide 3
      kinase/Akt pathway which led to phosphorylation and translocation of the MDM2 E3
      ligase resulting in increased p53 degradation. Ectopic expression of p53 restored
      luminal apoptosis in 14-3-3 zeta-overexpressing MCF10A acini in three-dimensional
      cultures. These data suggest that 14-3-3 zeta overexpression is a critical event
      in early breast disease, and down-regulation of p53 is one of the mechanisms by
      which 14-3-3 zeta alters MEC acini structure and increases the risk of breast
      cancer.

PMID- 18339857
TI  - The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and
      leptomeningeal spread.
AB  - Toward the goal of generating a mouse medulloblastoma model with increased tumor
      incidence, we developed a homozygous version of our ND2:SmoA1 model.
      Medulloblastomas form in 94% of homozygous Smo/Smo mice by 2 months of age. Tumor
      formation is, thus, predictable by age, before the symptomatic appearance of
      larger lesions. This high incidence and early onset of tumors is ideal for
      preclinical studies because mice can be enrolled before symptom onset and with a
      greater latency period before late-stage disease. Smo/Smo tumors also display
      leptomeningeal dissemination of neoplastic cells to the brain and spine, which
      occurs in many human cases. Despite an extended proliferation of granule neuron
      precursors (GNP) in the postnatal external granular layer (EGL), the internal
      granular layer formed normally in Smo/Smo mice and tumor formation occurred only
      in localized foci on the superficial surface of the molecular layer. Thus, tumor
      formation is not simply the result of over proliferation of GNPs within the EGL.
      Moreover, Smo/Smo medulloblastomas were transplantable and serially passaged in
      vivo, demonstrating the aggressiveness of tumor cells and their transformation
      beyond a hyperplastic state. The Smo/Smo model is the first mouse medulloblastoma
      model to show leptomeningeal spread. The adherence to human pathology, high
      incidence, and early onset of tumors thus make Smo/Smo mice an efficient model
      for preclinical studies.

PMID- 18339858
TI  - Oxidative stress is inherent in prostate cancer cells and is required for
      aggressive phenotype.
AB  - Reactive oxygen species (ROS) and the coupled oxidative stress have been
      associated with tumor formation. Several studies suggested that ROS can act as
      secondary messengers and control various signaling cascades. In the present
      studies, we characterized the oxidative stress status in three different prostate
      cancer cells (PC3, DU145, and LNCaP) exhibiting various degree of aggressiveness
      and normal prostate cells in culture (WPMY1, RWPE1, and primary cultures of
      normal epithelial cells). We observed increased ROS generation in cancer cells
      compared with normal cells, and that extramitochondrial source of ROS generator,
      NAD(P)H oxidase (Nox) systems, are associated with the ROS generation and are
      critical for the malignant phenotype of prostate cancer cells. Moreover,
      diphenyliodonium, a specific Nox inhibitor, blocked proliferation, modulated the
      activity of growth signaling cascades extracellular signal-regulated kinase
      (ERK)1/ERK2 and p38 mitogen-activated protein kinase as well as AKT protein
      kinase B, and caused cyclin B-dependent G(2)-M cell cycle arrest. We also
      observed higher degrees of ROS generation in the PC3 cells than DU145 and LNCaP,
      and that ROS generation is critical for migratory/invasiveness phenotypes.
      Furthermore, blocking of the ROS production rather than ROS neutralization
      resulted in decreased matrix metalloproteinase 9 activity as well as loss of
      mitochondrial potential, plausible reasons for decreased cell invasion and
      increased cell death. Taken together, these studies show, for the first time, the
      essential role of ROS production by extramitochondrial source in prostate cancer
      and suggest that therapies aimed at reducing ROS production might offer effective
      means of combating prostate cancer in particular, and perhaps other malignancies
      in general.

PMID- 18339859
TI  - Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer
      like methylome.
AB  - Estrogen imprinting is used to describe a phenomenon in which early developmental
      exposure to endocrine disruptors increases breast cancer risk later in adult
      life. We propose that long-lived, self-regenerating stem and progenitor cells are
      more susceptible to the exposure injury than terminally differentiated epithelial
      cells in the breast duct. Mammospheres, containing enriched breast progenitors,
      were used as an exposure system to simulate this imprinting phenomenon in vitro.
      Using MeDIP-chip, a methylation microarray screening method, we found that 0.5%
      (120 loci) of human CpG islands were hypermethylated in epithelial cells derived
      from estrogen-exposed progenitors compared with the non-estrogen-exposed control
      cells. This epigenetic event may lead to progressive silencing of tumor
      suppressor genes, including RUNX3, in these epithelial cells, which also occurred
      in primary breast tumors. Furthermore, normal tissue in close proximity to the
      tumor site also displayed RUNX3 hypermethylation, suggesting that this aberrant
      event occurs in early breast carcinogenesis. The high prevalence of estrogen
      induced epigenetic changes in primary tumors and the surrounding histologically
      normal tissues provides the first empirical link between estrogen injury of
      breast stem/progenitor cells and carcinogenesis. This finding also offers a
      mechanistic explanation as to why a tumor suppressor gene, such as RUNX3, can be
      heritably silenced by epigenetic mechanisms in breast cancer.

PMID- 18339860
TI  - Deletion of Yin Yang 1 protein in osteosarcoma cells on cell invasion and
      CXCR4/angiogenesis and metastasis.
AB  - We know that the Yin Yang 1 protein (YY1) overexpression is positively and
      strongly correlated with the degree of malignancy of bone tumors. Therefore, we
      questioned whether we could influence cell invasiveness by deleting YY1 in human
      osteosarcoma cells (SaOs-2), as tested in Matrigel-coated filters and metastasis
      implantation of such osteosarcoma cells in vivo, by serial analysis with nuclear
      magnetic resonance. Moreover, we focused our work on the chemokine receptor CXCR4
      and its inhibition by T22 antibody, as well as on systemic (direct in vivo assay)
      and computer-assisted imaging of angiogenesis-related metastasis. Results showed
      that cell invasiveness and metastasis implantation by wild-type SaOs-2 cells, as
      evaluated by histology and immunohistochemistry, are associated with up
      regulation of CXCR4 expression, which in turn was significantly reduced by T22.
      In addition, deletion of YY1 (siRNAYY1-SaOs-2) induced a significant decrease of
      cell invasion and metastasis growth. This phenomenon was associated with
      decreased vascular endothelial growth factor (VEGF)/angiogenesis and a complex
      rearrangement of the gene expression profile as evaluated by microarray analysis.
      In conclusion, YY1 and VEGF/CXCR4 seem to intervene in the pathogenesis of the
      malignant phenotype of osteosarcoma by acting on cell invasiveness and metastasis
      growth.

PMID- 18339861
TI  - Transforming growth factor-beta regulates mammary carcinoma cell survival and
      interaction with the adjacent microenvironment.
AB  - Transforming growth factor (TGF)-beta signaling has been associated with early
      tumor suppression and late tumor progression; however, many of the mechanisms
      that mediate these processes are not known. Using Cre/LoxP technology, with the
      whey acidic protein promoter driving transgenic expression of Cre recombinase
      (WAP-Cre), we have now ablated the type II TGF-beta receptor (T beta RII)
      expression specifically within mouse mammary alveolar progenitors. Transgenic
      expression of the polyoma virus middle T antigen, under control of the mouse
      mammary tumor virus enhancer/promoter, was used to produce mammary tumors in the
      absence or presence of Cre (T beta RII((fl/fl);PY) and T beta RII((fl/fl);PY;WC),
      respectively). The loss of TGF-beta signaling significantly decreased tumor
      latency and increased the rate of pulmonary metastasis. The loss of TGF-beta
      signaling was significantly correlated with increased tumor size and enhanced
      carcinoma cell survival. In addition, we observed significant differences in
      stromal fibrovascular abundance and composition accompanied by increased
      recruitment of F4/80(+) cell populations in T beta RII((fl/fl);PY;WC) mice when
      compared with T beta RII((fl/fl);PY) controls. The recruitment of F4/80(+) cells
      correlated with increased expression of known inflammatory genes including Cxcl1,
      Cxcl5, and Ptgs2 (cyclooxygenase-2). Notably, we also identified an enriched
      K5(+) dNp63(+) cell population in primary T beta RII((fl/fl);PY;WC) tumors and
      corresponding pulmonary metastases, suggesting that loss of TGF-beta signaling in
      this subset of carcinoma cells can contribute to metastasis. Together, our
      current results indicate that loss of TGF-beta signaling in mammary alveolar
      progenitors may affect tumor initiation, progression, and metastasis through
      regulation of both intrinsic cell signaling and adjacent stromal-epithelial
      interactions in vivo.

PMID- 18339862
TI  - PC3 human prostate carcinoma cell holoclones contain self-renewing tumor
      initiating cells.
AB  - Primary keratinocytes exhibit three typical clonal morphologies represented by
      holoclones, meroclones, and paraclones, with holoclones containing self-renewing
      stem cells, and meroclones and paraclones containing more mature and
      differentiated cells. Interestingly, long-term-cultured human epithelial cancer
      cells in clonal cultures also form holoclones, meroclones, and paraclones, and
      tumor cell holoclones have been hypothesized to harbor stem-like cells or cancer
      stem cells. However, the key question of whether tumor cell holoclones genuinely
      contain tumor-initiating cells has not been directly addressed. Here, using PC3
      human prostate carcinoma cells as a model, we provide direct experimental
      evidence that tumor cell holoclones contain stem-like cells that can initiate
      serially transplantable tumors. Importantly, holoclones derived from either
      cultured PC3 cells or holoclone-initiated tumors can be serially passaged and
      regenerate all three types of clones. In contrast, meroclones and paraclones
      cannot be continuously propagated and fail to initiate tumor development.
      Phenotypic characterizations reveal high levels of CD44, alpha(2)beta(1)
      integrin, and beta-catenin expression in holoclones, whereas meroclones and
      paraclones show markedly reduced expression of these stem cell markers. The
      present results have important implications in understanding morphologic
      heterogeneities and tumorigenic hierarchies in human epithelial cancer cells.

PMID- 18339863
TI  - Tumor cell dependence on Ran-GTP-directed mitosis.
AB  - Deregulated cell division is a hallmark of cancer, but whether tumor cells become
      dependent on specific mitotic mechanisms is not known. Here, we show that the
      small GTPase Ran, a regulator of mitotic spindle formation, is differentially
      overexpressed in human cancer as compared with normal tissues, in vivo. Acute
      silencing of Ran in various tumor cell types causes aberrant mitotic spindle
      formation, mitochondrial dysfunction, and apoptosis. This pathway does not
      require p53, Bax, or Smac, but is controlled by survivin as a novel Ran target in
      cancer. Conversely, loss of Ran in normal cells is well tolerated and does not
      result in mitotic defects or loss of cell viability. Therefore, tumor cells can
      become dependent on Ran signaling for cell division, and targeting this pathway
      may provide a novel and selective anticancer strategy.

PMID- 18339864
TI  - Triggering senescence programs suppresses Chk1 kinase and sensitizes cells to
      genotoxic stresses.
AB  - Depletion of the major heat shock protein Hsp72 leads to activation of the
      senescence program in a variety of tumor cell lines via both p53-dependent and
      p53-independent pathways. Here, we found that the Hsp72-depleted cells show
      defect in phosphorylation and activation of the protein kinase Chk1 by genotoxic
      stresses, such as UVC irradiation or camptothecin. Under these conditions,
      phosphorylation of Rad17 was also suppressed, whereas phosphorylation of p53 at
      Ser(15) was not affected, indicating a specific defect in phosphorylation of a
      subset of the ATR kinase substrates. Similarly, suppression of Chk1 activation
      was seen when senescence signaling was triggered by direct stimulation of p53,
      depletion of Cdc2, or overexpression of the cell cycle inhibitors p21 or p16.
      Thus, defect in Chk1 activation was not a consequence of the chaperone imbalance,
      but rather a downstream effect of activation of the senescence signaling.
      Inhibition of Chk1 was associated with inefficient inter-S phase checkpoint, as
      Hsp72 depleted cells failed to halt cell cycle progression upon UVC irradiation.
      Accordingly, sensitivity of cells to genotoxic stimuli after Hsp72 depletion was
      significantly enhanced. Thus, activation of the senescence signaling causes a
      defect in the DNA damage response manifested in increased sensitivity to
      genotoxic stresses.

PMID- 18339865
TI  - Gambogic acid inhibits angiogenesis and prostate tumor growth by suppressing
      vascular endothelial growth factor receptor 2 signaling.
AB  - Gambogic acid (GA), the main active compound of Gamboge hanburyi, has been
      previously reported to activate apoptosis in many types of cancer cell lines by
      targeting transferrin receptor and modulating nuclear factor-kappaB signaling
      pathway. Whether GA inhibits angiogenesis, which is crucial for cancer and other
      human diseases, remains unknown. Here, we found that GA significantly inhibited
      human umbilical vascular endothelial cell (HUVEC) proliferation, migration,
      invasion, tube formation, and microvessel growth at nanomolar concentration. In a
      xenograft prostate tumor model, we found that GA effectively inhibited tumor
      angiogenesis and suppressed tumor growth with low side effects using metronomic
      chemotherapy with GA. GA was more effective in activating apoptosis and
      inhibiting proliferation and migration in HUVECs than in human prostate cancer
      cells (PC3), suggesting GA might be a potential drug candidate in cancer therapy
      through angioprevention with low chemotoxicity. Furthermore, we showed that GA
      inhibited the activations of vascular endothelial growth factor receptor 2 and
      its downstream protein kinases, such as c-Src, focal adhesion kinase, and AKT.
      Together, these data suggest that GA inhibits angiogenesis and may be a viable
      drug candidate in antiangiogenesis and anticancer therapies.

PMID- 18339866
TI  - Proteinase-activated receptor-1-triggered activation of tumor progression locus-2
      promotes actin cytoskeleton reorganization and cell migration.
AB  - Tumor progression locus 2 (Tpl2), a mitogen-activated protein kinase kinase
      kinase (MAP3K) that is activated by provirus insertion in retrovirus-induced
      rodent lymphomas and mammary adenocarcinomas, is known to transduce Toll-like
      receptor, interleukin 1, tumor necrosis factor alpha, and CD40 signals and to
      play an important role in inflammation. Here we show that Tpl2 is also required
      for the transduction of cell migration and gene expression signals originating in
      the G-protein-coupled receptor proteinase-activated receptor 1 (PAR1). PAR1
      signals transduced by Tpl2 activate Rac1 and focal adhesion kinase, and they are
      required for reorganization of the actin cytoskeleton and cell migration. PAR1
      expressed in fibroblasts can be triggered by proteinases produced by tumor cells,
      and PAR1 expressed in tumor cells can be triggered by proteinases produced by
      fibroblasts. These data suggest that signals that regulate cell migration and
      gene expression flow between stromal and tumor cells in both directions and that
      Tpl2 plays a pivotal role in this process.

PMID- 18339867
TI  - The protein phosphatase activity of PTEN regulates SRC family kinases and
      controls glioma migration.
AB  - Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is mutated or
      lost in 60% to 70% of advanced gliomas and is associated with malignant
      phenotypic changes such as migration, which contribute to the morbidity and
      mortality of this disease. Most of the tumor suppressor function of PTEN has been
      attributed to its ability to dephosphorylate the second messenger,
      phosphatidylinositol 3,4,5-triphosphate, resulting in the biological control of
      the phosphatidylinositol 3-kinase (PI3K)/AKT pathway. Despite recent work
      suggesting that the protein phosphatase activity of PTEN controls glioma cell
      migration, the mechanisms by which this occurs are unclear. Herein, we show using
      glioma cell lines (U87MG and U373MG) stably transfected with wild-type PTEN or
      catalytically altered mutants of PTEN that PTEN controls integrin-directed
      migration in a lipid phosphatase, PI3K/AKT-independent manner. Confirming this
      observation, we show that the stable overexpression of COOH-terminal Src kinase,
      the physiologic negative regulator of SRC family kinases (SFK), or treatment with
      the SFK inhibitor PP1 abrogates glioma migration. The results provide direct
      evidence that the downstream effect of the protein phosphatase activity of PTEN
      is to suppress SFK and FYN, and to regulate RAC-GTPase activity after alpha(v)
      integrin stimulation. Furthermore, studying vitronectin-directed migration using
      (a) Fyn small interfering RNA and (b) astrocytes from Fyn heterozygous (+/-)
      mice, Pten heterozygous (+/-) mice, Pten and Fyn double heterozygous (+/-) mice,
      or Fyn knockout (-/-) mice confirmed a role of FYN in alpha(v) integrin-mediated
      haptotaxis in glial cells. Our combined results provide direct biochemical and
      genetic evidence that PTEN's protein phosphatase activity controls FYN kinase
      function in glioma cells and regulates migration in a PI3K/AKT-independent
      manner.

PMID- 18339868
TI  - Hypoxia-inducible factor-1 target genes as indicators of tumor vessel response to
      vascular endothelial growth factor inhibition.
AB  - Antiangiogenic therapy improves survival in patients with advanced stage cancers.
      Currently, there are no reliable predictors or markers for tumor vessel response
      to antiangiogenic therapy. To model effective antiangiogenic therapy, we
      disrupted the VEGF gene in three representative cancer cell lines. HCT116
      xenografts had low proportions of endothelial tubes covered by pericytes that
      stained with alpha-smooth muscle actin (SMA) antibody. Upon disruption of VEGF,
      HCT116(VEGF-/-) xenografts had significantly decreased tumor microvessel
      perfusion compared with their parental counterparts. Furthermore, HCT116(VEGF-/-)
      xenografts mounted a tumor-reactive response to hypoxia, characterized by the
      induction of hypoxia-inducible factor-1 (HIF-1) target genes. One highly induced
      protein was DPP4, a measurable serum protein that has well-described roles in
      cancer progression. In contrast, LS174T and MKN45 tumor xenografts had high
      proportion of endothelial tubes that were covered by SMA+ pericytes. Upon
      disruption of VEGF, LS174T(VEGF-/-) and MKN45(VEGF-/-) xenografts maintained
      tumor microvessel perfusion. As such, there were no changes in intratumoral
      hypoxia or HIF-1 alpha induction. Together, these data show that the extent of
      tumor vessel response to angiogenic inhibition could be correlated with (a) the
      preexisting coverage of tumor endothelial tubes with SMA+ pericytes and (b)
      differential tumor induction of HIF-1 target genes. The data further show that
      DPP4 is a novel marker of HIF-1 induction. Altogether, these preclinical findings
      suggest novel clinical trials for predicting and monitoring tumor vessel
      responses to antiangiogenic therapy.

PMID- 18339869
TI  - NOTCH3 signaling pathway plays crucial roles in the proliferation of ErbB2
      negative human breast cancer cells.
AB  - ErbB2-negative breast tumors represent a significant therapeutic hurdle because
      of a lack of effective molecular targets. Although NOTCH proteins are known to be
      involved in mammary tumorigenesis, the functional significance of these proteins
      in ErbB2-negative breast tumors is not clear. In the present study, we examined
      the expression of activated NOTCH receptors in human breast cancer cell lines,
      including ErbB2-negative and ErbB2-positive cell lines. Activated NOTCH1 and
      NOTCH3 proteins generated by gamma-secretase were detected in most of the cell
      lines tested, and both proteins activated CSL-mediated transcription. Down
      regulation of NOTCH1 by RNA interference had little or no suppressive effect on
      the proliferation of either ErbB2-positive or ErbB2-negative cell lines. In
      contrast, down-regulation of NOTCH3 significantly suppressed proliferation and
      promoted apoptosis of the ErbB2-negative tumor cell lines. Down-regulation of
      NOTCH3 did not have a significant effect on the ErbB2-positive tumor cell lines.
      Down-regulation of CSL also suppressed the proliferation of ErbB2-negative breast
      tumor cell lines, indicating that the NOTCH-CSL signaling axis is involved in
      cell proliferation. Finally, NOTCH3 gene amplification was detected in a breast
      tumor cell line and one breast cancer tissue specimen even though the frequency
      of NOTCH3 gene amplification was low (<1%). Taken together, these findings
      indicate that NOTCH3-mediated signaling rather than NOTCH1-mediated signaling
      plays an important role in the proliferation of ErbB2-negative breast tumor cells
      and that targeted suppression of this signaling pathway may be a promising
      strategy for the treatment of ErbB2-negative breast cancers.

PMID- 18339870
TI  - Regulation of CXCR4 by the Notch ligand delta-like 4 in endothelial cells.
AB  - Gene-targeting studies have shown that Delta-like 4 (Dll4) is required for normal
      embryonic vascular remodeling, but the mechanisms underlying Dll4 regulatory
      functions are not well defined. We generated primary human umbilical vascular
      endothelial cells that express Dll4 protein to study Dll4 function and previously
      showed that Dll4 down-regulates vascular endothelial growth factor (VEGF)
      receptor 2 and NRP1 expression and inhibits VEGF function. We now report that
      expression of Dll4 in endothelial cells inhibited attachment and migration to
      stromal-derived growth factor 1 (SDF1) chemokine. Cell surface, total protein,
      and mRNA levels of CXCR4, principal signaling receptor for SDF1, were
      significantly decreased in Dll4-transduced endothelial cells, attributable to a
      significant reduction of CXCR4 promoter activity. An immobilized recombinant
      extracellular portion of Dll4 (rhDLL4) was sufficient to down-regulate CXCR4 mRNA
      and protein, whereas protein levels of SDF1, VEGF, and RDC1 were unchanged. The
      gamma-secretase inhibitor L-685,458 significantly reconstituted CXCR4 mRNA in
      rhDLL4-stimulated endothelial cells. CXCR4 mRNA levels were significantly reduced
      in mouse xenografts of Dll4-transduced human gliomas compared with control
      gliomas, and vascular CXCR4 was not detected by immunohistochemistry in the
      enlarged vessels within the Dll4 gliomas. Thus, Dll4 may contribute to vascular
      differentiation and inhibition of the angiogenic response by regulating multiple
      receptor pathways.

PMID- 18339871
TI  - Adjuvant therapy with small hairpin RNA interference prevents non-small cell lung
      cancer metastasis development in mice.
AB  - Development of distant metastasis is the major reason for cancer-related deaths
      worldwide. Adjuvant therapy approaches after local therapies are most effective
      when specific targets are inhibited. Recently, we identified S100P overexpression
      as a strong predictor for metastasis development in early-stage non-small cell
      lung cancer (NSCLC) patients. Here, we show that S100P overexpression increased
      angiogenesis in and metastasis formation from s.c. xenotransplants of NSCLC
      cells. Plasmid-derived short hairpin RNAs (shRNA) were developed as specific
      adjuvant therapy. I.v. injected shRNA against S100P significantly decreased S100P
      protein expression in xenograft tumors and inhibited tumor angiogenesis in vivo.
      Metastasis formation 8 weeks after primary tumor resection was significantly
      reduced. Lung metastases developed in 31% of mice treated with S100P-targeting
      shRNAs compared with 64% in control shRNA-treated mice (P < 0.05). These findings
      suggest that RNA interference-based therapy approaches can be highly effective in
      the adjuvant setting.

PMID- 18339872
TI  - AXL is a potential target for therapeutic intervention in breast cancer
      progression.
AB  - Protein kinases play important roles in tumor development and progression. A
      variety of members of this family of signal transduction enzymes serve as targets
      for therapeutic intervention in cancer. We have identified the receptor tyrosine
      kinase (RTK) AXL as a potential mediator of motility and invasivity of breast
      cancer cells. AXL is expressed in most highly invasive breast cancer cells, but
      not in breast cancer cells of low invasivity. Ectopic expression of AXL was
      sufficient to confer a highly invasive phenotype to weakly invasive MCF7 breast
      cancer cells. Experimental inhibition of AXL signaling by a dominant-negative AXL
      mutant, an antibody against the extracellular domain of AXL, or short hairpin RNA
      knockdown of AXL decreased motility and invasivity of highly invasive breast
      cancer cells. To selectively interfere with cancer cell properties defining the
      rate of disease progression, we identified 3-quinolinecarbonitrile compounds,
      which displayed potent inhibitory activity against AXL and showed strong
      interference with motility and invasivity of breast cancer cells. Our findings
      validated the RTK AXL as a critical element in the signaling network that governs
      motility and invasivity of breast cancer cells, and allowed the identification of
      experimental anti-AXL small molecular inhibitors that represent lead substances
      for the development of antimetastatic breast cancer therapy.

PMID- 18339873
TI  - Enzastaurin, a protein kinase C beta inhibitor, suppresses signaling through the
      ribosomal S6 kinase and bad pathways and induces apoptosis in human gastric
      cancer cells.
AB  - Activation of protein kinase C (PKC) has been implicated in gastric
      carcinogenesis. Enzastaurin is an oral ATP-competitive inhibitor of the PKC beta
      isozyme. Although enzastaurin was initially advanced to the clinic based on its
      antiangiogenic activity, it is also known to have a direct effect on a variety of
      human cancer cells, inducing apoptosis by inhibiting the Akt signal pathway.
      However, data on enzastaurin for gastric cancer are limited. Therefore, this
      study was performed to assess the antitumor activity of enzastaurin on gastric
      cancer cells and to investigate the underlying antitumor mechanisms. Enzastaurin
      suppressed the proliferation of cultured gastric cancer cells and the growth of
      gastric carcinoma xenografts. Enzastaurin did not have an effect on gastric
      cancer cell cycle progression; however, it had a direct apoptosis-inducing effect
      through the caspase-mediated mitochondrial pathway. Glycogen synthase kinase
      3beta phosphorylation, a reliable pharmacodynamic marker of enzastaurin activity,
      and Akt phosphorylation were both decreased after treatment with enzastaurin.
      Although the p90 ribosomal S6 kinase (Rsk) was also dephosphorylated, Erk
      phosphorylation was not affected in the enzastaurin-treated gastric cancer cells.
      Enzastaurin activated Bad, one of the Bcl-2 proapoptotic proteins, through
      dephosphorylation at Ser(112), and depletion of Bad activity resulted in
      resistance to enzastaurin-induced apoptosis and cytotoxicity in gastric cancer
      cells. These data suggest that enzastaurin induces apoptosis through Rsk-mediated
      and Bad-mediated pathways, besides inhibiting the Akt signal cascade.
      Furthermore, enzastaurin had synergistic or additive effects when combined with 5
      fluorouracil, cisplatin, paclitaxel, or irinotecan. These results warrant further
      clinical investigation of enzastaurin for gastric cancer treatment.

PMID- 18339874
TI  - Mammalian target of rapamycin repression by 3,3'-diindolylmethane inhibits
      invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC3
      cells.
AB  - Platelet-derived growth factor-D (PDGF-D) is a newly recognized growth factor
      known to regulate many cellular processes, including cell proliferation,
      transformation, invasion, and angiogenesis. Recent studies have shown that PDGF-D
      and its cognate receptor PDGFR-beta are expressed in prostate tumor tissues,
      suggesting that PDGF-D might play an important role in the development and
      progression of prostate cancer. However, the biological role of PDGF-D in
      tumorigenesis remains elusive. In this study, we found that PDGF-D-overexpressing
      PC3 cells (PC3 cells stably transfected with PDGF-D cDNA and referred to as PC3
      PDGF-D) exhibited a rapid growth rate and enhanced cell invasion that was
      associated with the activation of mammalian target of rapamycin (mTOR) and
      reduced Akt activity. Rapamycin repressed mTOR activity and concomitantly
      resulted in the activation of Akt, which could attenuate the therapeutic effects
      of mTOR inhibitors. In contrast, B-DIM (BR-DIM from Bioresponse, Inc.; a
      chemopreventive agent) significantly inhibited both mTOR and Akt in PC3 PDGF-D
      cells, which were correlated with decreased cell proliferation and invasion.
      Moreover, conditioned medium from PC3 PDGF-D cells significantly increased the
      tube formation of human umbilical vein endothelial cells, which was inhibited by
      B-DIM treatment concomitant with reduced full-length and active form of PDGF-D.
      Our results suggest that B-DIM could serve as a novel and efficient
      chemopreventive and/or therapeutic agent by inactivation of both mTOR and Akt
      activity in PDGF-D-overexpressing prostate cancer.

PMID- 18339875
TI  - Antitumor activity and pharmacology of a selective focal adhesion kinase
      inhibitor, PF-562,271.
AB  - Cancer cells are characterized by the ability to grow in an anchorage-independent
      manner. The activity of the nonreceptor tyrosine kinase, focal adhesion kinase
      (FAK), is thought to contribute to this phenotype. FAK localizes in focal
      adhesion plaques and has a role as a scaffolding and signaling protein for other
      adhesion molecules. Recent studies show a strong correlation between increased
      FAK expression and phosphorylation status and the invasive phenotype of
      aggressive human tumors. PF-562,271 is a potent, ATP-competitive, reversible
      inhibitor of FAK and Pyk2 catalytic activity with a IC(50) of 1.5 and 14 nmol/L,
      respectively. Additionally, PF-562,271 displayed robust inhibition in an
      inducible cell-based assay measuring phospho-FAK with an IC(50) of 5 nmol/L. PF
      562,271 was evaluated against multiple kinases and displays >100x selectivity
      against a long list of nontarget kinases. PF-562,271 inhibits FAK phosphorylation
      in vivo in a dose-dependent fashion (calculated EC(50) of 93 ng/mL, total) after
      p.o. administration to tumor-bearing mice. In vivo inhibition of FAK
      phosphorylation (>50%) was sustained for >4 hours with a single p.o. dose of 33
      mg/kg. Antitumor efficacy and regressions were observed in multiple human s.c.
      xenograft models. No weight loss, morbidity, or mortality were observed in any in
      vivo experiment. Tumor growth inhibition was dose and drug exposure dependent.
      Taken together, these data show that kinase inhibition with an ATP-competitive
      small molecule inhibitor of FAK decreases the phospho-status in vivo, resulting
      in robust antitumor activity.

PMID- 18339876
TI  - Cannabinoids inhibit glioma cell invasion by down-regulating matrix
      metalloproteinase-2 expression.
AB  - Cannabinoids, the active components of Cannabis sativa L. and their derivatives,
      inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells
      and impairing tumor angiogenesis. It has also been reported that these compounds
      inhibit tumor cell spreading, but the molecular targets of this cannabinoid
      action remain elusive. Here, we evaluated the effect of cannabinoids on matrix
      metalloproteinase (MMP) expression and its effect on tumor cell invasion. Local
      administration of Delta(9)-tetrahydrocannabinol (THC), the major active
      ingredient of cannabis, down-regulated MMP-2 expression in gliomas generated in
      mice, as determined by Western blot, immunofluorescence, and real-time
      quantitative PCR analyses. This cannabinoid-induced inhibition of MMP-2
      expression in gliomas (a) was MMP-2-selective, as levels of other MMP family
      members were unaffected; (b) was mimicked by JWH-133, a CB(2) cannabinoid
      receptor-selective agonist that is devoid of psychoactive side effects; (c) was
      abrogated by fumonisin B1, a selective inhibitor of ceramide biosynthesis; and
      (d) was also evident in two patients with recurrent glioblastoma multiforme. THC
      inhibited MMP-2 expression and cell invasion in cultured glioma cells.
      Manipulation of MMP-2 expression by RNA interference and cDNA overexpression
      experiments proved that down-regulation of this MMP plays a critical role in THC
      mediated inhibition of cell invasion. Cannabinoid-induced inhibition of MMP-2
      expression and cell invasion was prevented by blocking ceramide biosynthesis and
      by knocking-down the expression of the stress protein p8. As MMP-2 up-regulation
      is associated with high progression and poor prognosis of gliomas and many other
      tumors, MMP-2 down-regulation constitutes a new hallmark of cannabinoid
      antitumoral activity.

PMID- 18339877
TI  - PIK3CA mutation/PTEN expression status predicts response of colon cancer cells to
      the epidermal growth factor receptor inhibitor cetuximab.
AB  - Cetuximab is a monoclonal antibody that targets the human epidermal growth factor
      receptor (EGFR). Although approved for use in EGFR-overexpressing advanced
      colorectal cancer, recent studies have shown a lack of association between EGFR
      overexpression and cetuximab response, requiring the identification of novel
      biomarkers predictive of response to this agent. To do so, 22 colon cancer cell
      lines were screened for cetuximab response in vitro and sensitive and resistant
      lines were identified. In sensitive cell lines, cetuximab induced a G(0)-G(1)
      arrest without inducing apoptosis. Notably, cetuximab-sensitive but not cetuximab
      resistant cell lines were preferentially responsive to EGF-stimulated growth.
      Whereas neither EGFR protein/mRNA expression nor gene copy number correlated with
      cetuximab response, examination of the mutation status of signaling components
      downstream of EGFR showed that cell lines with activating PIK3CA mutations or
      loss of PTEN expression (PTEN null) were more resistant to cetuximab than PIK3CA
      wild type (WT)/PTEN-expressing cell lines (14 +/- 5.0% versus 38.5 +/- 6.4%
      growth inhibition, mean +/- SE; P = 0.008). Consistently, PIK3CA mutant isogenic
      HCT116 cells showed increased resistance to cetuximab compared with PIK3CA WT
      controls. Furthermore, cell lines that were PIK3CA mutant/PTEN null and Ras/BRAF
      mutant were highly resistant to cetuximab compared with those without dual
      mutations/PTEN loss (10.8 +/- 4.3% versus 38.8 +/- 5.9% growth inhibition,
      respectively; P = 0.002), indicating that constitutive and simultaneous
      activation of the Ras and PIK3CA pathways confers maximal resistance to this
      agent. A priori screening of colon tumors for PTEN expression status and PIK3CA
      and Ras/BRAF mutation status could help stratify patients likely to benefit from
      this therapy.

PMID- 18339878
TI  - Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer
      activity.
AB  - Diphenyl difluoroketone (EF24), a molecule having structural similarity to
      curcumin, was reported to inhibit proliferation of a variety of cancer cells in
      vitro. However, the efficacy and in vivo mechanism of action of EF24 in
      gastrointestinal cancer cells have not been investigated. Here, we assessed the
      in vivo therapeutic effects of EF24 on colon cancer cells. Using hexosaminidase
      assay, we determined that EF24 inhibits proliferation of HCT-116 and HT-29 colon
      and AGS gastric adenocarcinoma cells but not of mouse embryo fibroblasts.
      Furthermore, the cancer cells showed increased levels of activated caspase-3 and
      increased Bax to Bcl-2 and Bax to Bcl-xL ratios, suggesting that the cells were
      undergoing apoptosis. At the same time, cell cycle analysis showed that there was
      an increased number of cells in the G(2)-M phase. To determine the effects of
      EF24 in vivo, HCT-116 colon cancer xenografts were established in nude mice and
      EF24 was given i.p. EF24 significantly suppressed the growth of colon cancer
      tumor xenografts. Immunostaining for CD31 showed that there was a lower number of
      microvessels in the EF24-treated animals coupled with decreased cyclooxygenase-2,
      interleukin-8, and vascular endothelial growth factor mRNA and protein
      expression. Western blot analyses also showed decreased AKT and extracellular
      signal-regulated kinase activation in the tumors. Taken together, these data
      suggest that the novel curcumin-related compound EF24 is a potent antitumor agent
      that induces caspase-mediated apoptosis during mitosis and has significant
      therapeutic potential for gastrointestinal cancers.

PMID- 18339879
TI  - Targeted delivery of gemcitabine to pancreatic adenocarcinoma using cetuximab as
      a targeting agent.
AB  - One of the key challenges in anticancer therapy is the toxicity and poor
      bioavailability of the anticancer drugs. Nanotechnology can play a pivotal role
      by delivering drugs in a targeted fashion to the malignant cells that will reduce
      the systemic toxicity of the anticancer drug. In this report, we show a stepwise
      development of a nanoparticle-based targeted delivery system for in vitro and in
      vivo therapeutic application in pancreatic cancer. In the first part of the
      study, we have shown the fabrication and characterization of the delivery system
      containing gold nanoparticle as a delivery vehicle, cetuximab as a targeting
      agent, and gemcitabine as an anticancer drug for in vitro application.
      Nanoconjugate was first characterized physico-chemically. In vitro targeting
      efficacy, tested against three pancreatic cancer cell lines (PANC-1, AsPC-1, and
      MIA Paca2) with variable epidermal growth factor receptor (EGFR) expression,
      showed that gold uptake correlated with EGFR expression. In the second part, we
      showed the in vivo therapeutic efficacy of the targeted delivery system.
      Administration of this targeted delivery system resulted in significant
      inhibition of pancreatic tumor cell proliferation in vitro and orthotopic
      pancreatic tumor growth in vivo. Tumor progression was monitored noninvasively by
      measuring bioluminescence of the implanted tumor cells. Pharmacokinetic
      experiments along with the quantitation of gold both in vitro and in vivo further
      confirmed that the inhibition of tumor growth was due to targeted delivery. This
      strategy could be used as a generalized approach for the treatment of a variety
      of cancers characterized by overexpression of EGFR.

PMID- 18339880
TI  - Therapy of advanced established murine breast cancer with a recombinant
      adenoviral ErbB-2/neu vaccine.
AB  - ErbB-2 (HER-2/neu) is a transforming oncogene expressed by a substantial fraction
      of breast cancers, and monoclonal antibody therapy directed toward this antigen
      is an established treatment modality. However, not all tumors respond, and with a
      monoclonal antibody directed to a single epitope, there is always the risk of
      tumor escape. Furthermore, passive antibody therapy requires continual treatment.
      Whereas cancer vaccines have prevented the growth of tumors, it has been far more
      difficult to treat large established tumors. Here, we show that vaccination with
      a recombinant adenovirus expressing a truncated ErbB-2 antigen can cure large
      established subcutaneous ErbB-2-expressing breast cancers in mice, and can also
      cure extensive established lung metastatic disease. We also show that the
      mechanism of protection involves antibody-mediated blockade of ErbB-2 function,
      independent of Fc receptors. We conclude that a vaccine inducing antibodies to a
      functional oncogenic receptor could have tremendous therapeutic potential against
      cancers overexpressing such molecules.

PMID- 18339881
TI  - Genome-wide analysis of the homeobox C6 transcriptional network in prostate
      cancer.
AB  - Homeobox transcription factors are developmentally regulated genes that play
      crucial roles in tissue patterning. Homeobox C6 (HOXC6) is overexpressed in
      prostate cancers and correlated with cancer progression, but the downstream
      targets of HOXC6 are largely unknown. We have performed genome-wide localization
      analysis to identify promoters bound by HOXC6 in prostate cancer cells. This
      analysis identified 468 reproducibly bound promoters whose associated genes are
      involved in functions such as cell proliferation and apoptosis. We have
      complemented these data with expression profiling of prostates from mice with
      homozygous disruption of the Hoxc6 gene to identify 31 direct regulatory target
      genes of HOXC6. We show that HOXC6 directly regulates expression of bone
      morphogenic protein 7, fibroblast growth factor receptor 2, insulin-like growth
      factor binding protein 3, and platelet-derived growth factor receptor alpha
      (PDGFRA) in prostate cells and indirectly influences the Notch and Wnt signaling
      pathways in vivo. We further show that inhibition of PDGFRA reduces proliferation
      of prostate cancer cells, and that overexpression of HOXC6 can overcome the
      effects of PDGFRA inhibition. HOXC6 regulates genes with both oncogenic and tumor
      suppressor activities as well as several genes such as CD44 that are important
      for prostate branching morphogenesis and metastasis to the bone microenvironment.

PMID- 18339882
TI  - Histamine suppresses fibulin-5 and insulin-like growth factor-II receptor
      expression in melanoma.
AB  - We previously showed that transgenic enhancement of histamine production in B16
      F10 melanomas strongly supports tumor growth in C57BL/6 mice. In the present
      study, gene expression profiles of transgenic mouse melanomas, secreting
      different amounts of histamine, were compared by whole genome microarrays. Array
      results were validated by real-time PCR, and genes showing histamine-affected
      behavior were further analyzed by immunohistochemistry. Regulation of histamine
      coupled genes was investigated by checking the presence and functional integrity
      of all four known histamine receptors in experimental melanomas and by
      administering histamine H1 receptor (H1R) and H2 receptor (H2R) antagonists to
      tumor-bearing mice. Finally, an attempt was made to integrate histamine-affected
      genes in known gene regulatory circuits by in silico pathway analysis. Our
      results show that histamine enhances melanoma growth via H1R rather than through
      H2R. We show that H1R activation suppresses RNA-level expression of the tumor
      suppressor insulin-like growth factor II receptor (IGF-IIR) and the
      antiangiogenic matrix protein fibulin-5 (FBLN5), decreases their intracellular
      protein levels, and also reduces their availability in the plasma membrane and
      extracellular matrix, respectively. Pathway analysis suggests that because plasma
      membrane-bound IGF-IIR is required to activate matrix-bound, latent transforming
      growth factor-beta1, a factor suggested to sustain FBLN5 expression, the data can
      be integrated in a known antineoplastic regulatory pathway that is suppressed by
      H1R. On the other hand, we show that engagement of H2R also reduces intracellular
      protein pools of IGF-IIR and FBLN5, but being a downstream acting
      posttranslational effect with minimal consequences on exported IGF-IIR and FBLN5
      protein levels, H2R is rather irrelevant compared with H1R in melanoma.

PMID- 18339883
TI  - Capture of tumor cell membranes by trogocytosis facilitates detection and
      isolation of tumor-specific functional CTLs.
AB  - The success of adoptive cell transfer in the treatment of metastatic cancer in
      humans is dependent on the selection of highly active tumor-specific cytotoxic T
      cells. We report here that CTLs capture membrane fragments from their targets
      while exerting cytotoxic activity and thus gain a detectable functional signature
      by which they can be identified. Fluorochrome labeling or biotinylation was used
      to tag tumor cells. CD8(+) T cells were coincubated with the tagged targets,
      sorted, and functionally evaluated. Our results show that membrane capture by
      CD8(+) lymphocytes is T-cell receptor dependent, epitope specific, and
      preferentially associated with highly cytotoxic clonal subsets. CTLs that
      captured membranes from unmodified melanoma exhibited enhanced cytotoxic activity
      against tumor cell lines and autologous melanoma. In a human melanoma in vivo
      model, adoptive transfer of membrane-capturing, peptide-specific T cells, but not
      noncapturing or bulk CD8(+) T cells, inhibits tumor progression. Membrane capture
      is therefore a signature of antigen-specific CTLs endowed with high functional
      avidity and may have direct relevance in the clinical application of adoptive
      immunotherapy.

PMID- 18339884
TI  - GM1 and tumor necrosis factor-alpha, overexpressed in renal cell carcinoma,
      synergize to induce T-cell apoptosis.
AB  - The ability to induce T-cell apoptosis is one mechanism by which tumors evade the
      immune system, although the molecules involved remain controversial. We found
      that renal cell carcinoma (RCC)-induced T-cell apoptosis was inhibited by >50%
      when cocultures were performed with ganglioside-depleted tumor cells, caspase-8
      negative lymphocytes, or anti-tumor necrosis factor-alpha (TNFalpha) antibodies,
      suggesting that tumor gangliosides synergize with signals delivered through
      TNFalpha death receptors to mediate T-cell killing. The synergy between tumor
      derived TNFalpha and the RCC-overexpressed ganglioside GM1 for killing resting T
      cells is corroborated by studies using purified GM1 and rTNF alpha, which
      indicate that a 48-hour pretreatment with the ganglioside optimally sensitizes
      the lymphocytes to a TNFalpha-induced apoptotic death. However, activated T
      cells, which synthesize TNFalpha themselves, can be killed by exogenous GM1
      alone. RelA-overexpressing lymphocytes are protected from GM1 plus TNFalpha
      mediated apoptosis, a finding consistent with our previous studies indicating
      that gangliosides inhibit nuclear factor-kappaB activation. These results are
      clinically relevant because, similar to T-cells cocultured with GM1
      overexpressing RCC lines, T cells isolated from the peripheral blood of patients
      with metastatic RCC are also heavily coated with that tumor-shed ganglioside.
      This population of patient cells, unlike T cells isolated from normal donors, is
      highly susceptible to apoptosis induced by rTNF alpha or by metastatic patient
      sera, which contain elevated levels of the cytokine. This report thus extends our
      previous studies by demonstrating that tumor-derived TNFalpha enhances RCC
      apoptogenicity not only by inducing ganglioside synthesis but also by initiating
      receptor-dependent apoptosis in T cells in which the nuclear factor-kappaB
      activation pathway has been inhibited by GM1.

PMID- 18339885
TI  - Dietary genistein inhibits metastasis of human prostate cancer in mice.
AB  - Dietary genistein has been linked to lower prostate cancer (PCa) mortality.
      Metastasis is the ultimate cause of death from PCa. Cell detachment and invasion
      represent early steps in the metastatic cascade. We had shown that genistein
      inhibits PCa cell detachment and cell invasion in vitro. Genistein-mediated
      inhibition of activation of focal adhesion kinase (FAK) and of the p38 mitogen
      activated protein kinase (MAPK)-heat shock protein 27 (HSP27) pathway has been
      shown by us to regulate PCa cell detachment and invasion effects, respectively.
      To evaluate the antimetastatic potential of genistein, we developed an animal
      model suited to evaluating antimetastatic drug efficacy. Orthotopically implanted
      human PC3-M PCa cells formed lung micrometastasis by 4 weeks in >80% of inbred
      athymic mice. Feeding mice dietary genistein before implantation led to blood
      concentrations similar to those measured in genistein-consuming men. Genistein
      decreased metastases by 96%, induced nuclear morphometric changes in PC3-M cells
      indicative of increased adhesion (i.e., decreased detachment) but did not alter
      tumor growth. Genistein increased tumor levels of FAK, p38 MAPK, and HSP27
      "promotility" proteins. However, the ratio of phosphorylated to total protein
      trended downward, indicating a failure to increase relative amounts of activated
      protein. This study describes a murine model of human PCa metastasis well suited
      for testing antimetastatic drugs. It shows for the first time that dietary
      concentrations of genistein can inhibit PCa cell metastasis. Increases in
      promotility proteins support the notion of cellular compensatory responses to
      antimotility effects induced by therapy. Studies of antimetastatic efficacy in
      man are warranted and are under way.

PMID- 18339886
TI  - Chemopreventive effect of silymarin on liver pathology in HBV X protein
      transgenic mice.
AB  - There are currently limited therapeutic regimens available for effective
      treatment of hepatocellular carcinoma (HCC). Silymarin is a naturally derived
      polyphenolic antioxidant with hepatoprotective properties and is very widely used
      in clinical application; however, effect of silymarin on spontaneous HCC has not
      been studied. Silymarin was evaluated for its efficacy against spontaneous
      carcinogenesis using the HBV X protein (HBx) transgenic model. Silymarin was p.o.
      given to the HBx transgenic mice from 4 to 6 weeks of age. Our data indicated
      that silymarin has therapeutic effects on the early stages of liver damage,
      reversing fatty changes and recovering liver histopathology in a dose-dependent
      manner. To study the chemopreventive effects on the later stages of
      carcinogenesis, the mice at 13 months were split into a precancerous group and a
      group with significant liver carcinogenesis. After silymarin was given to the
      precancerous mice from 13 to 16 months of age, in contrast to an 80% incidence of
      HCC development in the untreated transgenic mice, no HCC was detected in any of
      these mice. Nonetheless, small hyperplastic nodules were detected in 86% of these
      precancerous mice. In the second group with notable HCC, silymarin was unable to
      block cancer progression. Although silymarin did not affect HBx expression,
      intracellular reactive oxygen species levels were decreased, cell proliferation
      was stimulated, and hepatocyte ultrastructure was found to significantly recover.
      In conclusion, silymarin exerts beneficial effects on the early stages of liver
      pathogenesis, preventing and delaying liver carcinogenesis. This drug should be
      considered as a potential chemopreventive agent for HBV-related
      hepatocarcinogenesis.

PMID- 18339887
TI  - Silibinin inhibits colorectal cancer growth by inhibiting tumor cell
      proliferation and angiogenesis.
AB  - Herein, for the first time, we investigated in vivo efficacy and associated
      molecular biomarkers and mechanisms of a chemopreventive agent, silibinin,
      against human colorectal carcinoma (CRC) HT29 xenograft growth. Nude mice were
      implanted with HT29 cells and fed with vehicle (carboxymethyl cellulose or
      phosphatidylcholine) or 200 mg/kg/d dose of silibinin or 100 and 200 mg/kg/d
      doses of silybin-phytosome (5 days per week) for 32 days. Silibinin inhibited
      tumor growth that accounted for 48% (P = 0.002) decrease in tumor volume and 42%
      (P = 0.012) decrease in tumor weight at the end of the experiment without any
      adverse health effect. A stronger antitumor efficacy was observed with silybin
      phytosome preparation. Silibinin decreased proliferation index by 40% (P <
      0.001), increased apoptotic index by approximately 2-fold (P = 0.001), and
      reduced microvessel density by 36% (P = 0.001) in tumors. Antiproliferative and
      proapoptotic effects of silibinin were associated with down-regulation of
      extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt phosphorylation as
      well as cyclin D1 expression. Antiangiogenic effect of silibinin was coupled with
      a strong decrease in inducible nitric oxide synthase (NOS) and NOS3,
      cyclooxygenase-1 (COX-1) and COX-2, and hypoxia-inducing factor-1 alpha (HIF-1
      alpha) and vascular endothelial growth factor (VEGF). These findings suggest in
      vivo antitumor efficacy of silibinin against CRC involving its antiproliferative,
      proapoptotic, and antiangiogenic activities. The inhibition of ERK1/2 and Akt
      signaling may account for antiproliferative and proapoptotic effects, whereas
      down-regulation of NOS, COX, HIF-1 alpha, and VEGF expression could lead to
      antiangiogenic effect of silibinin against CRC. Overall, potential use of
      silibinin against human CRC could be suggested.

PMID- 18339889
TI  - Are skeletal muscles independent actuators? Force transmission from soleus muscle
      in the cat.
AB  - It is unclear if skeletal muscles act mechanically as independent actuators. The
      purpose of the present study was to investigate force transmission from soleus
      (SO) muscle for physiological lengths as well as relative positions in the intact
      cat hindlimb. We hypothesized that force transmission from SO fibers will be
      affected by length changes of its two-joint synergists. Ankle plantar flexor
      moment on excitation of the SO was measured for various knee angles (70-140
      degrees ). This involved substantial length changes of gastrocnemius and
      plantaris muscles. Ankle angle was kept constant (80 degrees -90 degrees ).
      However, SO ankle moment was not significantly affected by changes in knee angle;
      neither were half-relaxation time and the maximal rate of relaxation (P > 0.05).
      Following tenotomy, SO ankle moment decreased substantially (55 +/- 16%) but did
      not reach zero, indicating force transmission via connective tissues to the
      Achilles tendon (i.e., epimuscular myofascial force transmission). During
      contraction SO muscle shortened to a much greater extent than in the intact case
      (16.0 +/- 0.6 vs. 1.0 +/- 0.1 mm), which resulted in a major position shift
      relative to its synergists. If the SO was moved back to its position
      corresponding to the intact condition, SO ankle moment approached zero, and most
      muscle force was exerted at the distal SO tendon. Our results also suggested that
      in vivo the lumped intact tissues linking SO to its synergists are slack or are
      operating on the toe region of the stress-strain curve. Thus, within the
      experimental conditions of the present study, the intact cat soleus muscle
      appears to act mechanically as an independent actuator.

PMID- 18339890
TI  - Mechanical behavior of the quadriceps femoris muscle tendon unit during low-load
      contractions.
AB  - We examined the relationships between morphology and muscle-tendon dynamics of
      the quadriceps femoris muscle of 11 men using velocity-encoded phase-contrast
      magnetic resonance imaging (MRI). Thigh muscle electromyography and joint range
      of motion were first measured outside the MRI scanner during knee extension
      flexion tasks that were performed at a rate of 40 times/min with elastic bands
      providing peak resistance of 5.2 kp (SD 0.4) to the extension. The same movement
      was repeated inside the MRI scanner bore where tissue velocities and muscle
      morphology were recorded. The average displacement in the proximal and distal
      halves of the rectus femoris and vastus intermedius aponeuroses was different (P
      = 0.049), reflecting shortening (1.6%), but the tensile strain along the length
      of the aponeuroses was uniform. The aponeurosis behavior varied among
      individuals, and these individual patterns were best explained by the differences
      in relative cross-sectional area of rectus femoris to vastus muscles (r = 0.71, P
      = 0.014). During dynamic contraction, considerable deformation of muscles in the
      axial plane caused an anatomic measure such as muscle thickness to change
      differently (decrease or increase) in different sites of measurement. For
      example, when analyzed from the axial images, the vastus lateralis thickness did
      not change (P = 0.946) in the frontal plane through femur but increased in a 45
      degrees oblique plane between the frontal and sagittal planes (P = 0.004). The
      present observations of the heterogeneity and individual behavior emphasize the
      fact that single-point measurements do not always reflect the overall behavior of
      muscle-tendon unit.

PMID- 18339891
TI  - Design of a new variable-ventilation method optimized for lung recruitment in
      mice.
AB  - Variable ventilation (VV), characterized by breath-to-breath variation of tidal
      volume (Vt) and breathing rate (f), has been shown to improve lung mechanics and
      blood oxygenation during acute lung injury in many species compared with
      conventional ventilation (CV), characterized by constant Vt and f. During CV as
      well as VV, the lungs of mice tend to collapse over time; therefore, the goal of
      this study was to develop a new VV mode (VV(N)) with an optimized distribution of
      Vt to maximize recruitment. Groups of normal and HCl-injured mice were subjected
      to 1 h of CV, original VV (VV(O)), CV with periodic large breaths (CV(LB)), and
      VV(N), and the effects of ventilation modes on respiratory mechanics, airway
      pressure, blood oxygenation, and IL-1beta were assessed. During CV and VV(O),
      normal and injured mice showed regional lung collapse with increased airway
      pressures and poor oxygenation. CV(LB) and VV(N) resulted in a stable dynamic
      equilibrium with significantly improved respiratory mechanics and oxygenation.
      Nevertheless, VV(N) provided a consistently better physiological response. In
      injured mice, VV(O) and VV(N), but not CV(LB), were able to reduce the IL-1beta
      related inflammatory response compared with CV. In conclusion, our results
      suggest that application of higher Vt values than the single Vt currently used in
      clinical situations helps stabilize lung function. In addition, variable stretch
      patterns delivered to the lung by VV can reduce the progression of lung injury
      due to ventilation in injured mice.

PMID- 18339892
TI  - Cytokines secreted by IL-2-activated lymphocytes induce endogenous nitric oxide
      synthesis and apoptosis in macrophages.
AB  - IL-2-activated killer (LAK) cells secrete inflammatory cytokines such as IFN
      gamma and TNF-alpha, which can induce NO synthesis (NOS). In this study, we
      investigated IL-2-activated lymphocyte-mediated macrophage apoptosis via NOS. LAK
      cells and their culture supernatants induced NOS in murine macrophages. NOS was
      markedly inhibited by blocking antibodies to IFN-gamma and TNF-alpha, suggesting
      the key role of these lymphocyte cytokines in mediating NOS. Endogenous NO
      production inhibited macrophage proliferation and induced apoptosis in
      concordance with p53 accumulation and caspase-3 activation, processes that were
      inhibited by N(G)-monomethyl-l-arginine (a NOS inhibitor) and 2-(4-carboxyphenyl)
      4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (a NO scavenger). Our study
      demonstrated a novel, noncontact-dependent mechanism of macrophage suppression by
      IL-2-activated lymphocytes: induction of growth inhibition and apoptosis of
      macrophages as a result of endogenous NOS induced by cytokines secreted from IL-2
      activated lymphocytes.

PMID- 18339893
TI  - S100A8/A9 at low concentration promotes tumor cell growth via RAGE ligation and
      MAP kinase-dependent pathway.
AB  - The complex formed by two members of the S100 calcium-binding protein family,
      S100A8/A9, exerts apoptosis-inducing activity against various cells, especially
      tumor cells. Here, we present evidence that S100A8/A9 also has cell growth
      promoting activity at low concentrations. Receptor of advanced glycation end
      product (RAGE) gene silencing and cotreatment with a RAGE-specific blocking
      antibody revealed that this activity was mediated via RAGE ligation. To
      investigate the signaling pathways, MAPK phosphorylation and NF-kappaB activation
      were characterized in S100A8/A9-treated cells. S100A8/A9 caused a significant
      increase in p38 MAPK and p44/42 kinase phosphorylation, and the status of stress
      activated protein kinase/JNK phosphorylation remained unchanged. Treatment of
      cells with S100A8/A9 also enhanced NF-kappaB activation. RAGE small interfering
      RNA pretreatment abrogated the S100A8/A9-induced NF-kappaB activation. Our data
      indicate that S100A8/A9-promoted cell growth occurs through RAGE signaling and
      activation of NF-kappaB.

PMID- 18339894
TI  - A role for Leu118 of loop E in agonist binding to the alpha 7 nicotinic
      acetylcholine receptor.
AB  - Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels
      mediating fast cholinergic synaptic transmission in the brain and at
      neuromuscular junctions. We used the structure of the acetylcholine binding
      protein from Lymnaea stagnalis to model the chicken alpha7 agonist-binding
      domain. The initial models and a preliminary docking study suggested that
      position Leu118 may play an important role in determining agonist actions on
      alpha7. A prediction from these in silico studies, that L118E and L118D would
      retain binding to acetylcholine but L118K and L118R would not, was confirmed in
      electrophysiological studies on functional recombinant mutant receptors expressed
      in Xenopus laevis oocytes. The functional studies also demonstrated that residues
      at position 118 have a dramatic effect on the actions of imidacloprid (a partial
      agonist of wild-type alpha7 receptors) and its des-nitro derivative. Molecular
      dynamics simulations confirmed that Leu118 can strongly influence agonist binding
      and that the model was robust in terms of its prediction for acetylcholine
      binding. Together, the results indicate a role for Leu118 in influencing agonist
      actions on alpha7 nAChRs.

PMID- 18339895
TI  - Cul4A is required for hematopoietic cell viability and its deficiency leads to
      apoptosis.
AB  - In vitro studies indicate that Cul4A ubiquitin ligases target for ubiquitin
      mediated proteolysis regulators of cell-cycle progression, apoptosis,
      development, and DNA repair. In hematopoietic cell lines, studies by our group
      and others showed that Cul4A ligases regulate proliferation and differentiation
      in maturing myeloid and erythroid cells. In vivo, Cul4A-deficient embryos die in
      utero. Cul4A haploinsufficient mice are viable but have fewer erythroid and
      primitive myeloid progenitors. Yet, little more is known about Cul4A function in
      vivo. To examine Cul4A function in adults, we generated mice with interferon
      inducible deletion of Cul4A. Cul4A deficiency resulted in DNA damage and
      apoptosis of rapidly dividing cells, and mutant mice died within 3 to 10 days
      after induction with dramatic atrophy of the intestinal villi, bone marrow, and
      spleen, and with hematopoietic failure. Cul4A deletion in vivo specifically
      increased cellular levels of the Cul4A ligase targets Cdt1 and p27(Kip1) but not
      other known targets. Bone marrow transplantation studies with Cul4A deletion in
      engrafted cells specifically isolated analysis of Cul4A function to hematopoietic
      cells and resulted in hematopoietic failure. These recipients died within 9 to 11
      days, demonstrating that in hematopoietic cells, Cul4A is essential for survival.

PMID- 18339896
TI  - Induction of the IL-9 gene by HTLV-I Tax stimulates the spontaneous proliferation
      of primary adult T-cell leukemia cells by a paracrine mechanism.
AB  - The etiologic agent of adult T-cell leukemia (ATL) is human T cell lymphotropic
      virus type I (HTLV-I). The HTLV-I protein Tax alters gene expression, including
      those of cytokines and their receptors, which plays an important role in early
      stages of ATL. Here we demonstrate that expression of interleukin-9 (IL-9) is
      activated by Tax via an NF-kappaB motif in its proximal promoter, whereas IL-9
      receptor-alpha (IL-9Ralpha) expression is not induced by Tax. However, supporting
      a role for IL-9/IL-9Ralpha in ATL, a neutralizing monoclonal antibody directed
      toward IL-9Ralpha inhibited ex vivo spontaneous proliferation of primary ATL
      cells from several patients. Fluorescence-activated cell sorter analysis of
      freshly isolated peripheral blood mononuclear cells from these patients revealed
      high level expression of IL-9Ralpha on their CD14-expressing monocytes.
      Furthermore, purified T cells or monocytes alone from these patients did not
      proliferate ex vivo, whereas mixtures of these cell types manifested significant
      proliferation through a contact-dependent manner. Taken together, our data
      suggest that primary ATL cells, via IL-9, support the action of IL-9Ralpha/CD14
      expressing monocytes, which subsequently support the ex vivo spontaneous
      proliferation of malignant T cells. In summary, these data support a role for IL
      9 and its receptor in ATL by a paracrine mechanism.

PMID- 18339897
TI  - Synergistic interactions between interferon-gamma and TRAIL modulate c-FLIP in
      endothelial cells, mediating their lineage-specific sensitivity to thrombotic
      thrombocytopenic purpura plasma-associated apoptosis.
AB  - Microvascular endothelial cell (MVEC) injury coupled to progression of platelet
      microthrombi facilitated by ADAMTS13 deficiency is characteristic of idiopathic
      and HIV-linked thrombotic thrombocytopenic purpura (TTP). Cytokines capable of
      inducing MVEC apoptosis in vitro are up-regulated in both TTP and HIV infection.
      However, the concentrations of these cytokines required to elicit EC apoptosis in
      vitro are 2- to 3-log-fold greater than present in patient plasmas. We report
      that clinically relevant levels of tumor necrosis factor-related apoptosis
      inducing ligand (TRAIL) and interferon (IFN)-gamma act in synergy to induce
      apoptosis in dermal MVECs, but have no effect on large-vessel ECs or pulmonary
      MVECs. This reflects the tissue distribution of TTP lesions in vivo. Sensitivity
      to TTP plasma or TRAIL plus IFN-gamma is paralleled by enhanced ubiquitination of
      the caspase-8 regulator cellular FLICE-like inhibitory protein (c-FLIP),
      targeting it for proteasome degradation. c-FLIP silencing with anti-FLIP short
      interfering RNA (siRNA) in pulmonary MVECs rendered them susceptible to TTP
      plasma- and cytokine-mediated apoptosis, while up-regulation of c-FLIP by gene
      transfer partially protected dermal MVECs from such injury. TTP plasma-mediated
      apoptosis appears to involve cytokine-induced acceleration of c-FLIP degradation,
      sensitizing cells to TRAIL-mediated caspase-8 activation and cell death.
      Suppression of TRAIL or modulation of immunoproteasome activity may have
      therapeutic relevance in TTP.

PMID- 18339898
TI  - BCR-ABL1 alters SDF-1alpha-mediated adhesive responses through the beta2 integrin
      LFA-1 in leukemia cells.
AB  - Stromal-derived factor-1 (SDF-1) and its receptor, CXCR4, are essential for
      normal hematopoietic progenitor cell movement and adherence within the bone
      marrow microenvironment. In leukemia, the BCR-ABL1 oncoprotein inhibits SDF-1
      dependent cell trafficking within the bone marrow through a mechanism that is not
      fully understood. Here, we report that BCR-ABL1 in malignant cells constitutively
      increases expression of activation-dependent epitopes of the beta(2) integrin LFA
      1. This is associated with the complete loss of responsiveness of LFA-1 to SDF-1
      induced "inside-out" signaling involving CXCR4 and Lyn, leading to aberrant
      adhesive responses. These data provide a novel, LFA-1-mediated mechanism whereby
      BCR-ABL1 inhibits SDF-1 action in malignant progenitors.

PMID- 18339899
TI  - Distinct functional significance of Akt and mTOR constitutive activation in
      mantle cell lymphoma.
AB  - Functional characterization of signaling pathways that critically control mantle
      cell lymphoma (MCL) cell growth and survival is relevant to designing new
      therapies for this lymphoma. We herein demonstrate that the constitutive
      activation of Akt correlates with the expression of the phosphorylated, inactive
      form of PTEN. Phosphatidyl-inositol-3 kinase (PI3-K)/Akt or mammalian target of
      rapamycin (mTOR) inhibition decreased the growth of both primary MCL cultures and
      established cell lines and antagonizes the growth-promoting activity of CD40
      triggering and IL-4. These effects are mediated by nuclear accumulation of the
      p27(Kip1) inhibitor induced by down-regulation of the p45(Skp2) and Cks1
      proteins, which target p27(Kip1) for degradation. Moreover, Akt inhibition down
      regulated cyclin D1 by promoting its proteasome-dependent degradation driven by
      GSK-3. Intriguingly, mTOR inhibition affected cyclin D1 proteolysis only in MCL
      cells in which GSK-3 is under the direct control of mTOR, suggesting that
      different MCL subsets could be differently responsive to mTOR inhibition.
      Finally, PI3-K/Akt inhibitors, but not rapamycin, induced variable levels of
      caspase-dependent apoptosis and reduced telomerase activity. These results
      indicate that Akt and mTOR activation have distinct functional relevance in MCL
      and suggest that targeting Akt may result in more effective therapeutic effects
      compared with mTOR inhibition.

PMID- 18339900
TI  - Nutritional control of reproductive status in honeybees via DNA methylation.
AB  - Fertile queens and sterile workers are alternative forms of the adult female
      honeybee that develop from genetically identical larvae following differential
      feeding with royal jelly. We show that silencing the expression of DNA
      methyltransferase Dnmt3, a key driver of epigenetic global reprogramming, in
      newly hatched larvae led to a royal jelly-like effect on the larval developmental
      trajectory; the majority of Dnmt3 small interfering RNA-treated individuals
      emerged as queens with fully developed ovaries. Our results suggest that DNA
      methylation in Apis is used for storing epigenetic information, that the use of
      that information can be differentially altered by nutritional input, and that the
      flexibility of epigenetic modifications underpins, profound shifts in
      developmental fates, with massive implications for reproductive and behavioral
      status.

PMID- 18339901
TI  - Gate-variable optical transitions in graphene.
AB  - Two-dimensional graphene monolayers and bilayers exhibit fascinating electrical
      transport behaviors. Using infrared spectroscopy, we find that they also have
      strong interband transitions and that their optical transitions can be
      substantially modified through electrical gating, much like electrical transport
      in field-effect transistors. This gate dependence of interband transitions adds a
      valuable dimension for optically probing graphene band structure. For a graphene
      monolayer, it yields directly the linear band dispersion of Dirac fermions,
      whereas in a bilayer, it reveals a dominating van Hove singularity arising from
      interlayer coupling. The strong and layer-dependent optical transitions of
      graphene and the tunability by simple electrical gating hold promise for new
      applications in infrared optics and optoelectronics.

PMID- 18339902
TI  - Coherent dynamics of a single spin interacting with an adjustable spin bath.
AB  - Phase coherence is a fundamental concept in quantum mechanics. Understanding the
      loss of coherence is paramount for future quantum information processing. We
      studied the coherent dynamics of a single central spin (a nitrogen-vacancy
      center) coupled to a bath of spins (nitrogen impurities) in diamond. Our
      experiments show that both the internal interactions of the bath and the coupling
      between the central spin and the bath can be tuned in situ, allowing access to
      regimes with surprisingly different behavior. The observed dynamics are well
      explained by analytics and numerical simulations, leading to valuable insight
      into the loss of coherence in spin systems. These measurements demonstrate that
      spins in diamond provide an excellent test bed for models and protocols in
      quantum information.

PMID- 18339903
TI  - Impact of artificial reservoir water impoundment on global sea level.
AB  - By reconstructing the history of water impoundment in the world's artificial
      reservoirs, we show that a total of approximately 10,800 cubic kilometers of
      water has been impounded on land to date, reducing the magnitude of global sea
      level (GSL) rise by -30.0 millimeters, at an average rate of -0.55 millimeters
      per year during the past half century. This demands a considerably larger
      contribution to GSL rise from other (natural and anthropogenic) causes than
      otherwise required. The reconstructed GSL history, accounting for the impact of
      reservoirs by adding back the impounded water volume, shows an essentially
      constant rate of rise at +2.46 millimeters per year over at least the past 80
      years. This value is contrary to the conventional view of apparently variable GSL
      rise, which is based on face values of observation.

PMID- 18339905
TI  - The IPCC must maintain its rigor.

PMID- 18339904
TI  - Insect odorant receptors are molecular targets of the insect repellent DEET.
AB  - DEET (N,N-diethyl-meta-toluamide) is the world's most widely used topical insect
      repellent, with broad effectiveness against most insects. Its mechanism of action
      and molecular target remain unknown. Here, we show that DEET blocks
      electrophysiological responses of olfactory sensory neurons to attractive odors
      in Anopheles gambiae and Drosophila melanogaster. DEET inhibits behavioral
      attraction to food odors in Drosophila, and this inhibition requires the highly
      conserved olfactory co-receptor OR83b. DEET inhibits odor-evoked currents
      mediated by the insect odorant receptor complex, comprising a ligand-binding
      subunit and OR83b. We conclude that DEET masks host odor by inhibiting subsets of
      heteromeric insect odorant receptors that require the OR83b co-receptor. The
      identification of candidate molecular targets for the action of DEET may aid in
      the design of safer and more effective insect repellents.

PMID- 18339906
TI  - Scientific misconduct. Two papers from Korean lab found to lack 'scientific
      truth'.

PMID- 18339907
TI  - Biomedical research. $300 million in private money for new investigators.

PMID- 18339908
TI  - U.S. Congress. Physicist wins open Illinois seat.

PMID- 18339909
TI  - Scientific workplace. Indian government offers helping hand to women scientists.

PMID- 18339910
TI  - Neuroscience. Hiding from biting insects in plain scent.

PMID- 18339911
TI  - Developmental biology. Proposed frog ban makes a splash.

PMID- 18339912
TI  - Education. Spanish scientists question accreditation plan.

PMID- 18339913
TI  - Innovation. U.K.'s Royal Society ventures into funding start-up companies.

PMID- 18339914
TI  - Agriculture. Dueling visions for a hungry world.

PMID- 18339915
TI  - Graduate training. NSF fellowships called powerful tool for building the
      pipeline.

PMID- 18339916
TI  - Medicine. Blood-matching goes genetic.

PMID- 18339917
TI  - Computer science. Cryptologists cook up some hash for new 'bake-off'.

PMID- 18339918
TI  - Computer science. Hash of the future?

PMID- 18339919
TI  - The right pitch for saxophonists.

PMID- 18339920
TI  - Second Basket's negative impact.

PMID- 18339921
TI  - Going public with the scientific process.

PMID- 18339922
TI  - Hoyle's Role in B2FH.

PMID- 18339923
TI  - Science priorities. Inappropriate use and portrayal of chimpanzees.

PMID- 18339924
TI  - Planetary science. Observing our origins.

PMID- 18339925
TI  - Systems biology. Customized signaling circuits.

PMID- 18339926
TI  - Materials science. The new diamond age?

PMID- 18339927
TI  - Physics. This coincidence cannot be accidental.

PMID- 18339928
TI  - Archaeology. Standing on the shoulders of giants.

PMID- 18339929
TI  - Neuroscience. A quiescent working memory.

PMID- 18339930
TI  - The late Pleistocene dispersal of modern humans in the Americas.
AB  - When did humans colonize the Americas? From where did they come and what routes
      did they take? These questions have gripped scientists for decades, but until
      recently answers have proven difficult to find. Current genetic evidence implies
      dispersal from a single Siberian population toward the Bering Land Bridge no
      earlier than about 30,000 years ago (and possibly after 22,000 years ago), then
      migration from Beringia to the Americas sometime after 16,500 years ago. The
      archaeological records of Siberia and Beringia generally support these findings,
      as do archaeological sites in North and South America dating to as early as
      15,000 years ago. If this is the time of colonization, geological data from
      western Canada suggest that humans dispersed along the recently deglaciated
      Pacific coastline.

PMID- 18339931
TI  - Predators induce cloning in echinoderm larvae.
AB  - Asexual propagation (cloning) is a widespread reproductive strategy of plants and
      animals. Although larval cloning is well documented in echinoderms, identified
      stimuli for cloning are limited to those associated with conditions favorable for
      growth and reproduction. Our research shows that larvae of the sand dollar
      Dendraster excentricus also clone in response to cues from predators. Predator
      induced clones were smaller than uncloned larvae, suggesting an advantage against
      visual predators. Our results offer another ecological context for asexual
      reproduction: rapid size reduction as a defense.

PMID- 18339932
TI  - Organic molecules and water in the planet formation region of young circumstellar
      disks.
AB  - The chemical composition of protoplanetary disks is expected to hold clues to the
      physical and chemical processes that influence the formation of planetary
      systems. However, characterizing the gas composition in the planet formation
      region of disks has been a challenge to date. We report here that the
      protoplanetary disk within 3 astronomical units of AA Tauri possesses a rich
      molecular emission spectrum in the mid-infrared, indicating a high abundance of
      simple organic molecules (HCN, C2H2, and CO2), water vapor, and OH. These results
      suggest that water is abundant throughout the inner disk and that the disk
      supports an active organic chemistry.

PMID- 18339933
TI  - Superconductivity in hydrogen dominant materials: silane.
AB  - The metallization of hydrogen directly would require pressure in excess of 400
      gigapascals (GPa), out of the reach of present experimental techniques. The dense
      group IVa hydrides attract considerable attention because hydrogen in these
      compounds is chemically precompressed and a metallic state is expected to be
      achievable at experimentally accessible pressures. We report the transformation
      of insulating molecular silane to a metal at 50 GPa, becoming superconducting at
      a transition temperature of Tc = 17 kelvin at 96 and 120 GPa. The metallic phase
      has a hexagonal close-packed structure with a high density of atomic hydrogen,
      creating a three-dimensional conducting network. These experimental findings
      support the idea of modeling metallic hydrogen with hydrogen-rich alloy.

PMID- 18339934
TI  - Synthesis of macrocyclic copolymer brushes and their self-assembly into
      supramolecular tubes.
AB  - We report on an efficient route to design large macrocyclic polymers of
      controlled molar mass and narrow dispersity. The strategy is based on the
      synthesis of a triblock copolymer ABC, in which the long central block B is
      extended by two short A and C sequences bearing reactive antagonist functions.
      When reacted under highly dilute conditions, this precursor produces the
      corresponding macrocycle by intramolecular coupling of the A and C blocks.
      Chloroethyl vinyl ether was selected as the monomer for the central block B,
      because it can be readily derivatized into brushlike polymers by a grafting
      process. The corresponding macrocyclic brushes were decorated with polystyrene or
      randomly distributed polystyrene and polyisoprene branches. In a selective
      solvent for the polyisoprene branches, the macrocyclic brushes self-assemble into
      cylindrical tubes of up to 700 nanometers.

PMID- 18339935
TI  - Splitting of the 520-kilometer seismic discontinuity and chemical heterogeneity
      in the mantle.
AB  - Seismic studies indicate that beneath some regions the 520-kilometer seismic
      discontinuity in Earth's mantle splits into two separate discontinuities (at
      approximately 500 kilometers and approximately 560 kilometers). The discontinuity
      near 500 kilometers is most likely caused by the (Mg,Fe)2SiO4 beta-to-gamma phase
      transformation. We show that the formation of CaSiO3 perovskite from garnet can
      cause the deeper discontinuity, and by determining the temperature dependence for
      this reaction we demonstrate that regional variations in splitting of the
      discontinuity arise from variability in the calcium concentration of the mantle
      rather than from temperature changes. This discontinuity therefore is sensitive
      to large-scale chemical heterogeneity. Its occurrence and variability yield
      regional information on the fertility of the mantle or the proportion of recycled
      oceanic crust.

PMID- 18339936
TI  - The chlorine isotope composition of Earth's mantle.
AB  - Chlorine stable isotope compositions (delta37Cl) of 22 mid-ocean ridge basalts
      (MORBs) correlate with Cl content. The high-delta37Cl, Cl-rich basalts are highly
      contaminated by Cl-rich materials (seawater, brines, or altered rocks). The low
      delta37Cl, Cl-poor basalts approach the composition of uncontaminated, mantle
      derived magmas. Thus, most or all oceanic lavas are contaminated to some extent
      during their emplacement. MORB-source mantle has delta37Cl </= -1.6 per mil (per
      thousand), which is significantly lower than that of surface reservoirs
      (approximately 0 per thousand). This isotopic difference between the surface and
      deep Earth results from net Cl isotopic fractionation (associated with removal of
      Cl from the mantle and its return by subduction over Earth history) and/or the
      addition (to external reservoirs) of a late volatile supply that is 37Cl
      enriched.

PMID- 18339937
TI  - Caribbean reef development was independent of coral diversity over 28 million
      years.
AB  - The relationship between natural variations in coral species diversity, reef
      development, and ecosystem function on coral reefs is poorly understood. Recent
      coral diversity varies 10-fold among geographic regions, but rates of reef growth
      are broadly similar, suggesting that diversity is unimportant for reef
      development. Differences in diversity may reflect regional differences in long
      term biotic history in addition to environmental conditions. Using a combination
      of new and published fossil and stratigraphic data, we compared changes in coral
      diversity and reef development within the tropical western Atlantic over the past
      28 million years. Reef development was unrelated to coral diversity, and the
      largest reef tracts formed after extinction had reduced diversity by 50%. High
      diversity is thus not essential for the growth and persistence of coral reefs.

PMID- 18339938
TI  - Amyloid fibrils of the HET-s(218-289) prion form a beta solenoid with a
      triangular hydrophobic core.
AB  - Prion and nonprion forms of proteins are believed to differ solely in their three
      dimensional structure, which is therefore of paramount importance for the prion
      function. However, no atomic-resolution structure of the fibrillar state that is
      likely infectious has been reported to date. We present a structural model based
      on solid-state nuclear magnetic resonance restraints for amyloid fibrils from the
      prion-forming domain (residues 218 to 289) of the HET-s protein from the
      filamentous fungus Podospora anserina. On the basis of 134 intra- and
      intermolecular experimental distance restraints, we find that HET-s(218-289)
      forms a left-handed beta solenoid, with each molecule forming two helical
      windings, a compact hydrophobic core, at least 23 hydrogen bonds, three salt
      bridges, and two asparagine ladders. The structure is likely to have broad
      implications for understanding the infectious amyloid state.

PMID- 18339939
TI  - A retrotransposon-mediated gene duplication underlies morphological variation of
      tomato fruit.
AB  - Edible fruits, such as that of the tomato plant and other vegetable crops, are
      markedly diverse in shape and size. SUN, one of the major genes controlling the
      elongated fruit shape of tomato, was positionally cloned and found to encode a
      member of the IQ67 domain-containing family. We show that the locus arose as a
      result of an unusual 24.7-kilobase gene duplication event mediated by the long
      terminal repeat retrotransposon Rider. This event resulted in a new genomic
      context that increased SUN expression relative to that of the ancestral copy,
      culminating in an elongated fruit shape. Our discovery demonstrates that
      retrotransposons may be a major driving force in genome evolution and gene
      duplication, resulting in phenotypic change in plants.

PMID- 18339940
TI  - Evidence for karyogamy and exchange of genetic material in the binucleate
      intestinal parasite Giardia intestinalis.
AB  - The diplomonad parasite Giardia intestinalis contains two functionally equivalent
      nuclei that are inherited independently during mitosis. Although presumed to be
      asexual, Giardia has low levels of allelic heterozygosity, indicating that the
      two nuclear genomes may exchange genetic material. Fluorescence in situ
      hybridization performed with probes to an episomal plasmid suggests that plasmids
      are transferred between nuclei in the cyst, and transmission electron micrographs
      demonstrate fusion between cyst nuclei. Green fluorescent protein fusions of
      giardial homologs of meiosis-specific genes localized to the nuclei of cysts, but
      not the vegetative trophozoite. These data suggest that the fusion of nuclei, or
      karyogamy, and subsequently somatic homologous recombination facilitated by the
      meiosis gene homologs, occur in the giardial cyst.

PMID- 18339941
TI  - Direct visualization of horizontal gene transfer.
AB  - Conjugation allows bacteria to acquire genes for antibiotic resistance, novel
      virulence attributes, and alternative metabolic pathways. Using a fluorescent
      protein fusion, SeqA-YFP, we have visualized this process in real time and in
      single cells of Escherichia coli. We found that the F pilus mediates DNA transfer
      at considerable cell-to-cell distances. Integration of transferred DNA by
      recombination occurred in up to 96% of recipients; in the remaining cells, the
      transferred DNA was fully degraded by the RecBCD helicase/nuclease. The acquired
      integrated DNA was tracked through successive replication rounds and was found to
      occasionally split and segregate with different chromosomes, leading to the
      inheritance of different gene clusters within the cell lineage. The incidence of
      DNA splitting corresponds to about one crossover per cell generation.

PMID- 18339942
TI  - Using engineered scaffold interactions to reshape MAP kinase pathway signaling
      dynamics.
AB  - Scaffold proteins link signaling molecules into linear pathways by physically
      assembling them into complexes. Scaffolds may also have a higher-order role as
      signal-processing hubs, serving as the target of feedback loops that optimize
      signaling amplitude and timing. We demonstrate that the Ste5 scaffold protein can
      be used as a platform to systematically reshape output of the yeast mating MAP
      kinase pathway. We constructed synthetic positive- and negative-feedback loops by
      dynamically regulating recruitment of pathway modulators to an artificial binding
      site on Ste5. These engineered circuits yielded diverse behaviors: ultrasensitive
      dose response, accelerated or delayed response times, and tunable adaptation.
      Protein scaffolds provide a flexible platform for reprogramming cellular
      responses and could be exploited to engineer cells with novel therapeutic and
      biotechnological functions.

PMID- 18339943
TI  - Synaptic theory of working memory.
AB  - It is usually assumed that enhanced spiking activity in the form of persistent
      reverberation for several seconds is the neural correlate of working memory.
      Here, we propose that working memory is sustained by calcium-mediated synaptic
      facilitation in the recurrent connections of neocortical networks. In this
      account, the presynaptic residual calcium is used as a buffer that is loaded,
      refreshed, and read out by spiking activity. Because of the long time constants
      of calcium kinetics, the refresh rate can be low, resulting in a mechanism that
      is metabolically efficient and robust. The duration and stability of working
      memory can be regulated by modulating the spontaneous activity in the network.

PMID- 18339944
TI  - Science careers. Playing well with industry.

PMID- 18339945
TI  - Science careers. Business financing for your research.

PMID- 18339946
TI  - Science careers. Finding industry funding.

PMID- 18339947
TI  - Managing expectations: the art of finding and keeping loyal clients.

PMID- 18339948
TI  - Balancing veterinary students' and house officers' learning experiences in
      veterinary teaching hospitals.
AB  - Veterinary students at two large veterinary referral teaching hospitals were
      surveyed on their perceptions of competition with interns and residents for
      learning experiences during clinical instruction. Their responses led to an
      additional survey of a cohort of clinical educators on how this competition might
      be managed, what impedes effective management, and how progress toward an
      improved clinical learning environment might be measured. This article describes
      the results of the survey and discusses the nature of the competition and factors
      affecting the competitive learning environment. The results of this study should
      be expanded to include a larger cohort of veterinary students and an assessment
      of house officers' and faculty members' perceptions.

PMID- 18339949
TI  - Faculty expectations of veterinary students in clinical rotations.
AB  - Expectations of veterinary students during clinical rotations should be developed
      with the goal of bettering the veterinary profession as a whole. This article
      outlines five areas of expectations for the veterinary professional: treating
      colleagues with respect, providing excellent care for patients and clients,
      developing and maintaining skill sets to support intellectual curiosity and
      continued professional development, and improving upon and using self-care and
      life-balance skills.

PMID- 18339950
TI  - Applicant expectations and decision factors for jobs and careers in food-supply
      veterinary medicine.
AB  - This article examines the job expectations of applicants as reported by
      recruiters interviewing food-supply veterinary medicine (FSVM) candidates and the
      career-choice decision factors used by year 3 and 4 veterinary students pursuing
      careers in FSVM. The responses of 1,047 veterinary recruiters and 270 year 3 and
      4 students with a food-supply focus from 32 colleges of veterinary medicine in
      the United States and Canada were examined. Recruiters were asked to report the
      two most important job factors applicants took into account when deciding to
      accept an offer; students were asked the two most important reasons for choosing
      a career in FSVM and the two most important benefits of working as a food-supply
      veterinarian. Recruiters reported that high salaries and good benefits are the
      two most important decision factors. Interest in the food-animal career area and
      a desire for a rural, outdoor lifestyle were the top reasons students gave for
      choosing an FSVM career. Students saw the enjoyment of working with and helping
      producers and food animals as the most important benefits of a career in FSVM.

PMID- 18339951
TI  - Meeting the expectations of referring veterinarians.
AB  - Veterinary teaching hospitals (VTHs) have traditionally obtained most of their
      patient and client base through the referral process. This worked well until the
      recent explosive growth of specialty practices, which compete not only for
      patients but also for faculty and graduating residents. Veterinary schools have
      had to meet this challenge by increasing both efficiency and the quality of
      services provided to referring veterinarians. Practitioners refer mainly because
      of discomfort with a case and the belief that clients will get better treatment
      at a referral hospital than they themselves can provide. Practitioners choose not
      to refer because of geography, perceived cost, or lack of confidence in the
      services offered. Referring veterinarians expect regular communication about
      services offered, access to receiving clinicians for consultation, convenient
      scheduling, and efficient communication and follow-up from the receiving
      veterinarian. They also expect the relationship between them and their clients to
      be maintained and enhanced. Receiving veterinarians expect a summary letter and
      copies of all relevant records, including radiographs. They also expect the
      client to have been informed about the approximate costs of referral. VTHs can
      develop better relationships with referring veterinarians through education,
      newsletters, referral guides, practice visits, and Web sites. Inadequate
      communication and lack of involvement on the part of the referring veterinarian
      are the major impediments to efficient referrals and practice growth.

PMID- 18339952
TI  - Teaching veterinary students using shelter animals.
AB  - Veterinary teaching hospitals (VTHs) are experiencing case-load trends that have
      negatively affected efforts to prepare students for entry-level veterinary
      practice, particularly in the area of technical skills training. This article
      examines the clinical training available to veterinary students through a variety
      of collaborative shelter models. Benefits and potential problems related to
      initiating a collaborative shelter clinical training program are reviewed.
      Collaborative efforts between animal shelters and veterinary schools can provide
      crucial opportunities for outreach teaching initiatives, particularly for
      teaching medical and surgical skills.

PMID- 18339953
TI  - Emergency medicine clerkship: a joining of private-practice referral veterinary
      medicine with an academic institution.
AB  - Novel approaches to the clinical training of veterinary students in many
      disciplines are being sought by veterinary colleges. In 2004, the University of
      Florida College of Veterinary Medicine approached the Small Animal Department and
      Florida Veterinary Specialists (FVS) in Tampa with a proposal to jointly design
      and run an elective clerkship in emergency medicine. The program would focus on
      providing increased emergency case exposure in a real-world environment to
      interested third- and fourth-year veterinary students. The purpose would be to
      better prepare these students for emergent cases while increasing their overall
      level of clinical confidence. This article reviews in detail the clerkship
      structure, its objectives, and the logistics of training and support at FVS. In
      this instance, the academic-private institution partnership has been successful
      in providing effective learning for veterinary students over the last three
      years. This clerkship structure may serve as a template for other institutions
      exploring alternatives to the traditional clinical training of veterinary
      students.

PMID- 18339954
TI  - Community-based clinical veterinary education at Western University of Health
      Sciences.
AB  - This article describes a distributed model clinical curriculum developed by the
      College of Veterinary Medicine, Western University of Health Sciences (CVMWU),
      and presents outcome data for the 2005/2006 academic year. Extramural clinical
      education requires close institutional involvement, including planning,
      formulation of learning objectives, selection of partner sites with numbers
      compatible with teaching needs, training of clinical preceptors, faculty
      commitment, administrative support, and ongoing assessment. Extramural delivery
      of the CVMWU clinical curriculum is facilitated by its geographical location in
      close proximity to participating sites and by an admissions process designed to
      select students judged likely to succeed in a student-centered learning
      environment. Outcome data collected from students and clinical preceptors
      supports the conclusion that year 3 of the curriculum was successfully delivered.

PMID- 18339955
TI  - Satellite teaching hospitals and public-private collaborations in veterinary
      medical clinical education.
AB  - Veterinary teaching hospitals (VTHs) are facing more and greater challenges than
      at any time in the past. Changes in demand, expanding information, improving
      technology, an evolving workforce, declining state support, and an increasingly
      diverse consumer base have combined to render many traditional VTH modes of
      operation obsolete. In pursuit of continued success in achieving their academic
      mission, VTHs are exploring new business models, including innovative
      collaborations with the private sector. This report provides details on existing
      models for public-private collaboration at several colleges and schools of
      veterinary medicine, including those at Kansas State University, Purdue
      University, the University of Florida, and Tufts University. Although each of
      these institutions' models is unique, several commonalities exist, related to
      expansion of the case load available for teaching, the potential positive impact
      on recruitment and retention of clinical faculty, and the potential for easing
      financial pressures on the associated VTH. These new models represent innovative
      approaches that work to meet many of the key emerging challenges facing VTHs
      today.

PMID- 18339956
TI  - Cooperating with industry to teach food-animal medicine.
AB  - Cooperative programs with agribusiness offer opportunities for colleges of
      veterinary medicine to expand their instructional programs in agricultural
      practice. Agribusinesses associated with livestock agriculture recognize the
      importance of veterinary medicine in maintaining a vibrant and successful
      industry. Stewardship of corporate support involves close communication with
      advocates within the companies, providing them with documentation of the
      potential effects of corporate investments. This article describes the creation
      of the Michigan State University (MSU) Training Center for Dairy Professionals, a
      key aspect of which was the identification of innovative and productive areas of
      mutual interest and benefit. In addition to supporting the dairy industry by
      training veterinary students, the program offers specific benefits to investors,
      including the use of MSU facilities and direct participation in veterinary
      instruction.

PMID- 18339957
TI  - The future of specialty practice.
AB  - The delivery of veterinary care to companion animals by board-certified clinical
      specialists in private practice in the United States has grown dramatically since
      1990. Virtually all mid-sized to large metropolitan areas are served by clinical
      specialists, frequently in multiple locations. Private specialty practice is
      highly fragmented, and very few data exist regarding the dynamics of this segment
      of the profession. This article is based on the personal opinions of the author,
      acquired through observation and experience.

PMID- 18339958
TI  - The scientific component of residency training.
AB  - This article focuses on the role of veterinary teaching hospitals (VTHs) at
      public and private colleges and universities in the growth and nurturing of
      today's veterinary clinician scientists, who will assume the ranks of tomorrow's
      veterinary academic faculty. Virtually all residency programs offer some level of
      scientific education and training concurrently or sequentially with professional
      clinical training; approximately half (51%) include, or at least offer, the
      opportunity to obtain advanced scientific degrees (MS/MSc and/or PhD). If
      veterinary schools and colleges are the gatekeepers for the veterinary
      profession, then VTHs are the gatekeepers for the profession's scientific
      development, defining the future role of veterinary medicine in society. Although
      struggling to find their place in a financially challenging and competitive
      environment fueled by the demand for more and better clinical services, VTHs are
      in a potentially strong position to capitalize on the uniqueness of their faculty
      and academic resources and thus make an unparalleled contribution to the
      scientific evolution of the veterinary profession.

PMID- 18339959
TI  - Making the academy more attractive to new teacher-scholars.
AB  - The majority of faculty members in veterinary medicine are white men; the student
      base, however, is increasingly composed of white women. Faculty and students of
      color are few. Part of the problem in attracting and retaining new teacher
      scholars is that the current generation has different beliefs about the
      importance of work and home, places dissimilar weights on various workplace
      dimensions, and has more complicated lives than prior generations of faculty.
      Thus, a culture clash arises when young faculty work in academic institutions
      with outmoded policies and practices. This article explores the key aspects of
      the structure and culture of the academy and offers ideas for making the
      workplace more attractive to new faculty.

PMID- 18339960
TI  - Veterinary teaching hospitals: current challenges and pathways for the future.
AB  - University-based veterinary teaching hospitals must change to maintain their
      viability. A number of factors both internal and external to universities and the
      veterinary profession have contributed to the need for change. A task force
      formed by the Association of American Veterinary Medical Colleges and the
      American Association of Veterinary Clinicians was convened to identify the issues
      and propose individual and collective strategies for the future. Primary issues
      include a shortage of faculty and staff, the nature of the case load, the need
      for fiscal management strategies, and the need to manage stakeholder
      expectations. The majority of the proposed strategies for the future will be
      managed individually by the colleges. Proposed collective strategies center on
      increasing the number of specialists and improving recruitment and retention of
      faculty and staff.

PMID- 18339961
TI  - Part I: twenty-year literature overview of veterinary and allopathic medicine.
AB  - Over the last 20 years, numerous reports, symposia, and workshops have focused on
      the challenges and changes facing veterinary and allopathic medicine. Many of
      these have specifically considered the changing economic and demographic profiles
      of the health professions, the specific roles of health professionals in society,
      and the importance of professional curricula in meeting changing professional and
      societal needs. Changing curricula to address future demands is a common thread
      that runs through all of these reports. Future demands most consistently noted
      include the fact that modern veterinary curricula must emphasize the acquisition
      of skills, values, and attitudes in addition to the acquisition of knowledge.
      Skills relating to business management, strong interpersonal communication, and
      problem solving have often been noted as lacking in current curricula.
      Furthermore, future curricula must allow for greater diversification and
      "specialization" among veterinary students; should promote greater opportunities
      for an emphasis on public health and population medicine, including food safety,
      food security, and bio- and agro-terrorism; and should motivate students to be
      active learners who possess strong lifelong learning skills and attitudes.

PMID- 18339962
TI  - Part II: directions and objectives of curriculum structure at veterinary medical
      and other health professions schools.
AB  - This article surveys reports on various models and methods of curriculum
      structure and directions of health professions schools in North America over the
      past 20 years, with particular emphasis on veterinary and allopathic medical
      schools. The importance of administrative and faculty leadership, a clear sense
      of vision, recognition that curricula must change to meet societal needs, and
      continual, extensive communication and collaboration are discussed as important
      keys to successfully navigating curriculum reform. The advantages of central
      versus departmental management of the curriculum are noted with respect to
      implementing curricular change. Investment in faculty development is essential to
      ensure sustained cultural and curricular change. As instructional methodology
      changes, new and better methods of assessing student performance must be
      developed, with timely and appropriate feedback. Barriers to curriculum change
      are inevitable; effective strategies must be designed and implemented to navigate
      these barriers. The future of education in the health professions is clearly in
      the hands of the educators who prepare future health professionals.

PMID- 18339963
TI  - Part III: a case study at the Virginia-Maryland Regional College of Veterinary
      Medicine.
AB  - This article presents a history of curriculum revision. Internal and external
      factors prompting the initial curriculum review included the Pew Report, a vision
      in the college for reform, and faculty retreats focusing on curriculum. The
      reformed curriculum was designed around a "core plus elective" strategy and was
      implemented following development by faculty representatives and approval by
      college and university levels of review. The curriculum was reviewed after being
      revised and after new courses were first offered, with further review of a few
      courses with specific challenges. Outcomes assessment was performed and
      curricular adjustments made. Challenges that arose during the process included
      organizing and documenting content as well as communicating the content and
      philosophy of the new curriculum to the various affected constituencies. A
      summary of factors considered essential to the successful design, implementation,
      and review of the new curriculum is presented; the majority of these factors
      would be applicable to reforms at other institutions.

PMID- 18339964
TI  - The first-year veterinary student and mental health: the role of common
      stressors.
AB  - The present study evaluated the impact of academic and non-academic stressors on
      depression levels in a longitudinal investigation of 78 first-year veterinary
      medical students enrolled at Kansas State University (KSU). Students completed
      the Center for Epidemiological Studies Depression Scale during their first and
      second semesters to evaluate the dependent variable, depression. Students
      provided information about specific stressors and relevant demographic variables
      that yielded independent variables. One-third of veterinary medical students
      surveyed in their first and second semesters reported depression levels above the
      clinical cut-off; 15% of the sample experienced an increase in depression of at
      least one standard deviation, despite the apparent stability of the proportion of
      students experiencing significant depressive symptoms. Students whose depression
      scores increased by one standard deviation or who maintained scores above the
      clinical cut-off score were identified as struggling. Struggling students
      reported more first-semester homesickness and academic concerns, along with
      difficulty fitting in with peers and poorer perceived physical health during the
      second semester. This study helped to identify those students most prone to
      develop or maintain concerning depression scores. The discussion section
      addresses specific suggestions for intervening with struggling students.

PMID- 18339965
TI  - Facilitating appreciation of anatomical variation and development of teamwork
      skills in the gross anatomy laboratory using a cadaver reassignment system.
AB  - Developing a mental map of the body in three dimensions incorporating normal
      anatomical variations is a challenge for students of gross anatomy. Acquisition
      of this ability is facilitated by frequently reassigning students to work on
      different specimens in gross anatomy laboratories, a significant departure from
      traditional teaching strategies. This article analyzes student and faculty
      experiences with a reassignment system over a six-year period, including effects
      on early professional development and students' attitudes toward the cadavers.
      Students were strongly supportive of the method, noting that specimen
      reassignments facilitated learning, encouraged dissection skill building, and
      fostered collaborative interactions. Students' perception of the value of the
      contribution of each cadaver to their education was preserved and, for many,
      enhanced. Frequent specimen reassignments offer an opportunity to model public
      accountability for work and some aspects of the relationships between multiple
      health care teams caring for a patient.

PMID- 18339966
TI  - Effective information design for PDAs in veterinary medical education.
AB  - Until recently, personal digital assistants (PDAs) have been ignominiously
      characterized as a solution without a problem. To many, they were glorified
      versions of calendars, address books, notepads, and calculators that appeared
      only minimally more useful than their paper predecessors. Today's PDAs cater to a
      wider range of mobile computing needs, especially in the veterinary field, where
      they support mobile, information-centric work. Despite the PDA's resurgent
      popularity, hardware constraints limit its wide-scale integration. Most notably,
      small screen sizes limit the PDA designers who compose texts, videos, and images
      for PDA delivery. This article addresses the problem of designing for small
      screens by re-characterizing the issue as an information design problem rather
      than a hardware problem. By analyzing how fourth-year students in a veterinary
      medicine program use their PDAs in their clinical education, we offer suggestions
      for designing information to meet their needs.

PMID- 18339967
TI  - Continuing veterinary medical education needs and delivery preferences of Alberta
      veterinarians.
AB  - The questionnaire component of a continuing-education needs assessment of Alberta
      veterinarians is described. A questionnaire about work characteristics, topic
      priorities, and program delivery preferences was mailed to all licensed Alberta
      veterinarians, 54% of whom responded. Topic-priority data were factor analyzed,
      and differences in priorities were examined using multivariate analysis of
      variance (MANOVA). Seven learning areas emerged: veterinary medicine,
      professionalism and practice management, animal welfare, livestock practice and
      epidemiology, prophylaxis and therapeutics, specialty diagnostics, and
      theriogenology. Associations between delivery preferences and work
      characteristics were sought using MANOVA and contingency tables analysis.
      Significant differences were identified in learning-area priorities and preferred
      program types and times when respondents were grouped by species focus, and there
      were significant associations between respondents' location and their preferred
      learning locations. There were no significant associations between location or
      practice size and preferred program type. Group differences support the need for
      events tailored by species focus. Delivery preferences suggest that workload and
      distance are barriers to attendance, although face-to-face events were
      universally preferred.

PMID- 18339968
TI  - Developing veterinary colleges and leaders: a whole-system approach.
AB  - The current environment in higher education calls for increasingly progressive
      leadership and management. This report describes the efforts of the College of
      Veterinary Medicine (CVM) at Michigan State University (MSU) to strengthen its
      leadership using a whole-system approach. Developing a leadership culture is the
      responsibility of leaders, and the pursuit of such a culture requires
      considerable and justifiable investment of time, energy, and resources. The
      volatile and changing environment in which colleges of veterinary medicine exist
      makes creating such a culture imperative if society's needs are to be
      successfully met. Noteworthy cultural change has occurred within the MSU CVM
      because of the efforts described here.

PMID- 18339969
TI  - New role of resistin in lipopolysaccharide-induced liver damage in mice.
AB  - Studies in rodents suggest that the adipocytokine resistin causes insulin
      resistance via impairing normal insulin signaling. However, in humans, resistin
      may play a more important role in inflammation than in insulin resistance.
      Whether resistin contributes to inflammation in rodents is unclear. Therefore,
      the purpose of the present study was to determine the effect of resistin exposure
      on the basal and stimulated [lipopolysaccharide (LPS)] inflammatory response in
      mouse liver in vivo. Resistin alone had no major effects on hepatic expression of
      insulin-responsive genes, either in the presence or absence of LPS. Although it
      had no effect alone, resistin significantly enhanced hepatic inflammation and
      necrosis caused by LPS. Resistin increased expression of proinflammatory genes,
      e.g., plasminogen activator inhibitor (PAI)-1, and activity of mitogen-activated
      protein (MAP) kinase, extracellular signal-regulated kinase 1/2, caused by LPS,
      but had little effect on anti-inflammatory gene expression. Resistin also
      enhanced fibrin deposition (an index of hemostasis) caused by LPS. The increase
      in PAI-1 expression, fibrin deposition, and liver damage caused by LPS + resistin
      was almost completely prevented either by inhibiting the coagulation cascade,
      hirudin, or by blocking MAP kinase signaling, U0126 [1,4-diamino-2,3-dicyano-1,4
      bis(2-aminophenylthio) butadiene], indicating that these pathways play a causal
      role in observed enhanced liver damage caused by resistin. Taken together, the
      augmentation of LPS-induced liver damage caused by resistin seems to involve, at
      least in part, up-regulation of hepatic inflammation via mechanisms most likely
      involving the coagulation cascade and fibrin accumulation. These data also
      suggest that resistin may have proinflammatory roles in mouse liver independent
      of its effects on insulin signaling, analogous to previous work in humans.

PMID- 18339970
TI  - Extracellular signal-regulated kinase activation mediates mitochondrial
      dysfunction and necrosis induced by hydrogen peroxide in renal proximal tubular
      cells.
AB  - Although tubular necrosis in acute renal failure is associated with excessive
      production of reactive oxygen species (ROS), such as hydrogen peroxide (H2O2),
      the mechanism of ROS-induced cell necrosis remains poorly understood. In this
      study, we examined the role of the extracellular signaling-regulated kinase (ERK)
      pathway in H2O2-induced necrosis of renal proximal tubular cells (RPTC) in
      primary culture. Exposure of 60 to 70% confluent RPTC to 1 mM H2O2 for 3 h
      resulted in 44% necrotic cell death, as measured by trypan blue uptake, and
      inactivation of mitogen-activated protein kinase kinase (MEK), the upstream
      activator of ERK, by either 1,4-diamino-2,3-dicyano-1,4-bis[2
      aminophenylthio]butadiene (U0126) or 2-(2'-amino-3'-methoxyphenyl)-oxanaphthalen
      4-one (PD98059) or overexpression of dominant-negative mutant of MEK1, inhibited
      cell death. In contrast, overexpression of active MEK1 enhanced H2O2-induced cell
      death. H2O2 treatment led to the loss of mitochondrial membrane potential (MMP)
      in RPTC, which was decreased by U0126 and PD98059. Furthermore, inhibition of the
      MEK/ERK pathway decreased oxidant-mediated ERK1/2 activation and mitochondrial
      swelling in isolated renal cortex mitochondria. However, treatment with
      cyclosporin A (CsA), a mitochondrial permeability transition blocker, did not
      suppress RPTC necrotic cell death, loss of MMP, and mitochondrial swelling. We
      suggest that ERK is a critical mediator of mitochondrial dysfunction and necrotic
      cell death of renal epithelial cells following oxidant injury. Oxidant-induced
      necrotic cell death was mediated by a CsA-insensitive loss of MMP that is
      regulated by the ERK pathway.

PMID- 18339971
TI  - The use of occupation isoboles for analysis of a response mediated by two
      receptors: M2 and M3 muscarinic receptor subtype-induced mouse stomach
      contractions.
AB  - Smooth muscle contains multiple muscarinic receptor subtypes, including M2 and
      M3. M2 receptors outnumber M3 receptors. Based on the potency of subtype
      selective anticholinergics, contraction is mediated by the M3 subtype. However,
      results from knockout (KO) mice show that the M2 receptor mediates approximately
      45% of the contractile response produced by the M3 receptor. The traditional
      theory of one receptor mediating a response does not allow assessment of
      interactions between receptors when more than one receptor participates in a
      response. Our study was performed using a novel analysis method based on dual
      receptor occupancy to determine how M2 and M3 receptor subtypes interact to
      mediate contraction in mouse stomach. Cumulative carbachol concentration
      contractile responses were determined for wild-type, M2-KO, and M3-KO stomach
      body smooth muscle. Using affinity constants for carbachol at M2 and M3
      cholinergic receptors, the concentration values were converted to fractional
      receptor occupation. The resulting occupation-effect relations showed maximum
      effects for the M2 and M3 subtypes, respectively. These occupation-effect
      relations allow determination of the additive (expected) isobole based on this
      dual occupancy, thereby providing a curve (mathematically derived) for comparison
      against the experimentally derived value in wild type. The actual values
      determined experimentally in the wild type were not statistically significantly
      different from that predicted by the isobole. This confirms that the interaction
      between these mutually occupied receptors is additive. The new method of analysis
      also expands the traditional Schild theory that was based on a single receptor
      type to which the agonist and antagonist bind.

PMID- 18339972
TI  - Diabetes, fasting glucose levels, and risk of ischemic stroke and vascular
      events: findings from the Northern Manhattan Study (NOMAS).
AB  - OBJECTIVE: There is insufficient randomized trial data to support evidence-based
      recommendations for tight control of fasting blood glucose (FBG) among diabetic
      subjects in primary stroke prevention. We explored the relationship between FBG
      among diabetic subjects and risk of ischemic stroke in a multiethnic prospective
      cohort. RESEARCH DESIGN AND METHODS: Medical and social data and FBG values were
      collected for 3,298 stroke-free community residents: mean age +/- SD was 69 +/-10
      years; 63% were women, 21% were white, 24% were black, and 53% were Hispanic; and
      follow-up was 6.5 years. Baseline FBG levels were categorized: 1) elevated FBG:
      history of diabetes and FBG >or=126 mg/dl (7.0 mmol/l); 2) target FBG: history of
      diabetes and FBG <126 mg/dl (7.0 mmol/l); or 3) no diabetes/reference group. Cox
      models were used to calculate hazard ratios (HRs) and 95% CI for ischemic stroke
      and vascular events. RESULTS: In the Northern Manhattan Study, 572 participants
      reported a history of diabetes and 59% (n = 338) had elevated FBG. Elevated FBG
      among diabetic subjects was associated with female sex (P < 0.04), Medicaid (P =
      0.01), or no insurance (P = 0.03). We detected 190 ischemic strokes and 585
      vascular events. Diabetic subjects with elevated FBG (HR 2.7 [95% CI 2.0-3.8])
      were at increased risk of stroke, but those with target FBG levels (1.2 [0.7
      2.1]) were not, even after adjustment. A similar relationship existed for
      vascular events: elevated FBG (2.0 [1.6-2.5]) and target FBG (1.3 [0.9-1.8].
      CONCLUSIONS: This prospective cohort study provides evidence for the benefits of
      tighter glucose control for primary stroke prevention.

PMID- 18339973
TI  - Adipokines and incident type 2 diabetes in an Aboriginal Canadian [corrected]
      population: the Sandy Lake Health and Diabetes Project.
AB  - OBJECTIVE: The aim of this study was to investigate associations of adiponectin,
      leptin, C-reactive protein (CRP), interleukin (IL)-6, and serum amyloid A (SAA),
      individually or in combinations, with risk of incident type 2 diabetes in a
      Aboriginal Canadian [corrected] population. RESEARCH DESIGN AND METHODS: Of the
      606 Sandy Lake Health and Diabetes Project cohort subjects who were free of
      diabetes at baseline, 540 (89.1%) participated in 10-year follow-up assessments.
      Concentrations of fasting adiponectin, leptin, CRP, IL-6, SAA, and covariates
      were measured at baseline. Fasting glucose and a 75-g oral glucose tolerance test
      were obtained at baseline and follow-up to determine incident type 2 diabetes,
      defined as clinically diagnosed type 2 diabetes or as fasting plasma glucose > or
      =7.0 mmol/l or 2-h postload plasma glucose > or =11.1 mmol/l at follow-up.
      RESULTS: Low adiponectin, high leptin, and low adiponectin-to-leptin ratio at
      baseline were associated with increased risk of incident type 2 diabetes after
      adjustment for age, sex, triglycerides, HDL cholesterol, hypertension, and
      impaired glucose tolerance (odds ratio 0.63 [95% CI 0.48-0.83], 1.50 [1.02-2.21],
      and 0.54 [0.37-0.77], respectively). When the models were additionally adjusted
      for waist circumference or BMI, however, only low adiponectin remained
      significantly associated with increased incident diabetes (0.68 [0.51-0.90]).
      Combinations of leptin, CRP, IL-6, and/or SAA with adiponectin, assessed using
      either the ratio or joint effects, did not improve diabetes prediction.
      CONCLUSIONS: Low baseline adiponectin is associated with increased risk of
      incident type 2 diabetes independent of leptin, CRP, IL-6, SAA, and metabolic
      syndrome variables including obesity.

PMID- 18339974
TI  - Comparison of the numerical and clinical accuracy of four continuous glucose
      monitors.
AB  - OBJECTIVE: The purpose of this study was to compare the numerical and clinical
      accuracy of four continuous glucose monitors (CGMs): Guardian, DexCom, Navigator,
      and Glucoday. RESEARCH DESIGN AND METHODS: Accuracy data for the four CGMs were
      collected in two studies: Study 1 enrolled 14 adults with type 1 diabetes at the
      University of Virginia (UVA), Charlottesville, Virginia; study 2 enrolled 20
      adults with type 1 diabetes at the Profil Institute for Metabolic Research,
      Neuss, Germany. All participants underwent hyperinsulinemic clamps including 1.5
      2 h of maintained euglycemia at 5.6 mmol/l followed by descent into hypoglycemia,
      sustained hypoglycemia at 2.5 mmol/l for 30 min, and recovery. Reference blood
      glucose sampling was performed every 5 min. The UVA study tested Guardian,
      DexCom, and Navigator simultaneously; the Profil study tested Glucoday. RESULTS:
      Regarding numerical accuracy, during euglycemia, the mean absolute relative
      differences (MARDs) of Guardian, DexCom, Navigator, and Glucoday were 15.2, 21.2,
      15.3, and 15.6%, respectively. During hypoglycemia, the MARDs were 16.1, 21.5,
      10.3, and 17.5%, respectively. Regarding clinical accuracy, continuous glucose
      error grid analysis (CG-EGA) revealed 98.9, 98.3, 98.6, and 95.5% zones A + B
      hits in euglycemia. During hypoglycemia, zones A + B hits were 84.4, 97.0, and
      96.2% for Guardian, Navigator, and Glucoday, respectively. Because of frequent
      loss of sensitivity, there were insufficient hypoglycemic DexCom data to perform
      CG-EGA. CONCLUSIONS: The numerical accuracy of Guardian, Navigator, and Glucoday
      was comparable, with an advantage to the Navigator in hypoglycemia; the numerical
      errors of the DexCom were approximately 30% larger. The clinical accuracy of the
      four sensors was similar in euglycemia and was higher for the Navigator and
      Glucoday in hypoglycemia.

PMID- 18339975
TI  - Role of adiponectin in matching of fetal and placental weight in mothers with
      type 1 diabetes.
AB  - OBJECTIVE: To assess the association of fetal hormones with placental growth and
      fetal weight-to-placental weight ratio index (FPI) in pregnancies complicated by
      maternal diabetes. RESEARCH DESIGN AND METHODS: We conducted a prospective study
      using umbilical venous blood samples taken at birth from 122 offspring of mothers
      with type 1 diabetes (OT1D) and 46 control subjects. RESULTS: Placental weight (P
      = 0.009) and gestation-adjusted birth weight (P < 0.001) were increased in OT1D,
      but FPI was unaltered (P = 0.33). Placental weight correlated with birth weight
      (P < 0.001) and cord leptin (P < 0.001) in control subjects and OT1D, with
      further relationships with cord insulin, IGF-1, IGF-binding protein-3 (IGFBP-3),
      and triceps and subscapular thickness in OT1D. FPI was associated with
      adiponectin in both groups, even after adjustment for confounders. CONCLUSIONS:
      Placental and fetal growth show a parallel increase in mothers with type 1
      diabetes. The possible role of adiponectin in matching of fetal and placental
      growth merits further study.

PMID- 18339976
TI  - Glucose intolerance and diabetes are observed in the long-term follow-up of
      nonpancreatectomized patients with persistent hyperinsulinemic hypoglycemia of
      infancy due to mutations in the ABCC8 gene.
AB  - OBJECTIVE: To report the long-term follow-up of three nonpancreatectomized
      patients with persistent hyperinsulinemic hypoglycemia of infancy due to
      mutations in the ABCC8 gene. RESEARCH DESIGN AND METHODS: Oral glucose tolerance
      test (OGTT) and venous 24-h glucose-insulin profile were performed yearly from
      adolescence. RESULTS: Patient 1 (now aged 31 years) developed insulin-dependent
      diabetes at the age of 25 years. In patient 2 (now aged 17 years), impaired
      fasting glucose and a diabetic OGTT response with normal A1C values have been
      observed since the age of 10 years. In patient 3 (now aged 24 years), intolerant
      OGTT response and hyperglycemic episodes with normal A1C have been observed since
      the age of 16 years. All patients presented relatively low insulin levels during
      hyperglycemia, normal BMI, and negative autoantibodies (GAD antibody, insulinoma
      associated protein 2, and islet cell antibody). CONCLUSIONS: Development of
      glucose metabolism impairment ranging from glucose intolerance to insulin
      dependent diabetes is observed in the evolution of these patients.

PMID- 18339977
TI  - Treatment satisfaction and quality of life with insulin glargine plus insulin
      lispro compared with NPH insulin plus unmodified human insulin in individuals
      with type 1 diabetes.
AB  - OBJECTIVE: The purpose of this study was to compare quality of life (QoL) and
      treatment satisfaction using insulin glargine plus insulin lispro with that using
      NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed
      with multiple injection regimens. RESEARCH DESIGN AND METHODS: As part of a 32
      week, five-center, two-way crossover study in 56 individuals with type 1 diabetes
      randomized to evening insulin glargine plus mealtime insulin lispro or to NPH
      insulin (once or twice daily) plus mealtime unmodified human insulin, the
      Diabetes Treatment Satisfaction Questionnaire (DTSQ) and the Audit of Diabetes
      Dependent Quality of Life questionnaire were completed at baseline and at weeks
      16 and 32, with additional interim DTSQ measurements. RESULTS: For all patients
      combined, the mean baseline present QoL score was 1.3, reflecting "good" QoL.
      Present QoL improved with glargine + lispro but did not change with NPH + human
      insulin (1.6 +/- 0.1 [mean +/- SEM] vs. 1.3 +/- 0.1, difference 0.3 [95% CI 0.1
      0.6]; P = 0.014). Baseline mean average weighted impact score (AWI) of diabetes
      on QoL was -1.8, indicating a negative impact of diabetes on QoL. The AWI score
      at end point improved significantly with glargine + lispro but changed little
      with NPH + human insulin (-1.4 +/- 0.1 vs. -1.7 +/- 0.1, 0.3 [0.0-0.6]; P =
      0.033). Treatment satisfaction (DTSQ 36-0 scale score) at end point was markedly
      greater with glargine plus lispro compared with that for NPH plus human insulin
      (32.2 +/- 3.4 vs. 23.9 +/- 7.2, 8.6 [6.5-10.6]; P < 0.001). CONCLUSIONS: Insulin
      glargine plus insulin lispro improves treatment satisfaction, reduces the
      negative impact of diabetes on QoL, and improves QoL in comparison with NPH
      insulin plus unmodified human insulin in type 1 diabetes.

PMID- 18339978
TI  - Succession--a critical issue for the agricultural sciences.

PMID- 18339979
TI  - Investigating the effects of dietary probiotic feeding regimens on broiler
      chicken production and Campylobacter jejuni presence.
AB  - An experiment was conducted to investigate the effect of restricted feeding of a
      commercially available probiotic diet on production/processing performance,
      Campylobacter jejuni prevalence, and organ weights in broiler chickens. Five
      hundred forty 1-d-old broiler chicks were randomly assigned to a control or a
      direct-fed microbial (PrimaLac, DFM) diet and subjected to ad libitum full-fed
      (A), restricted 8-h (R), or skip-a-day (S) feeding regimens. Each of the 6
      treatments was replicated 3 times with 15 male and 15 female chicks per pen for
      49 d. Significant (P<0.05) differences between BW in the control and DFM groups
      with regard to feed type were found at d 7 (A), female d 21 (R) male and females,
      and d 49 (A and S) male and females. Body weights of males in the control group
      were significantly higher than the DFM (A) and differed by regimens (A>R>S) at d
      49, whereas weights of females did not differ in regimens A and S. Body weight in
      the control females of regimen R was significantly higher than those in regimens
      A and S. Carcass yield was significantly higher for males in the control regimen
      A, 78.1 vs. 74.6% for the DFM regimen A; however, females did not differ
      significantly in this regimen, but did so in regimen S with 72.6 vs. 69.0%. The
      gizzard weights were significantly higher for broilers exposed to S and R
      regimens when compared with the A regimen. The prevalence of C. jejuni in the DFM
      treated broilers regimen R was lower (33 vs. 60% positive) for the control group
      at 21 d. The weekly BW throughout the study reflected many variations, but
      broiler chickens receiving the control feed on regimen A performed better than
      those receiving the DFM feed. From the present results, it was concluded that
      supplementation of DFM reduced the presence of C. jejuni but had no significant
      effect on the growth performance of broilers; however, there were some
      significant trends regarding sex, feed, and feeding methods on the performance
      results.

PMID- 18339980
TI  - Serotonergic mediation of aggression in high and low aggressive chicken strains.
AB  - Serotonin (5-HT) regulates aggressive behavior via binding to its receptors, such
      as 5-HT1A and 1B, in humans and rodents. Here we investigate the heritable
      components of 5-HT regulation of aggressiveness in chickens, utilizing 3 distinct
      genetic strains. In this study, we used 2 divergently selected strains (high and
      low group productivity and survivability, respectively; HGPS and LGPS) and a
      third strain, Dekalb XL (DXL), an aggressive out-group. Hens were paired within
      the same strain. At 24 wk of age, the subordinate of each pair received a daily
      i.p. injection of NAN-190 (0.5 mg/kg, a 5-HT1A antagonist), GR-127935 (0.5 mg/kg,
      a 5-HT1B antagonist), or saline (control) for 5 consecutive days. Frequency of
      aggressive behaviors was increased in the hens of DXL and LGPS treated with 5
      HT1A antagonist and in the HGPS hens treated with 5-HT1B antagonist. The 5-HT1B
      antagonist-treated HGPS hens and 5-HT1A antagonist-treated LGPS hens also
      displayed increased feather pecking, but neither antagonist had an effect on
      feather pecking of DXL hens. This may suggest that multiple mediating factors
      alter feather pecking behaviors. Among the controls, LGPS hens have higher
      epinephrine levels than HGPS or DXL hens, indicative of the inferior stress
      coping ability of LGPS hens. Treatment with 5-HT1B antagonist reduced epinephrine
      in LGPS hens but not in DXL or HGPS hens, suggesting a role of 5-HT1B in stress
      regulation in LGPS hens. The results provide evidence for different heritable
      serotonergic mediation of aggressive behaviors and stress coping in chickens.

PMID- 18339981
TI  - Effects of housing system and cold stress on heterophil-to-lymphocyte ratio,
      fluctuating asymmetry, and tonic immobility duration of chickens.
AB  - The purpose of this study was to analyze the effect of housing system and cold
      stress on the heterophil-to-lymphocyte ratio, the fluctuating asymmetry, and the
      tonic immobility duration of chickens. In experiment 1, hens (n=120; 36 wk old)
      from 5 Spanish breeds and a White Leghorn population, which had been housed in
      pens with or without access to an outdoor area from 20 wk of age, were used. The
      effect of housing system on heterophil-to-lymphocyte ratio varied from breed to
      breed, differences between housing systems being significant (P<0.05) in 2
      breeds. In these breeds (Red-Barred Vasca and Birchen Leonesa), heterophil-to
      lymphocyte ratio was significantly greater in hens housed in deep litter. Housing
      effect was significant for the relative asymmetry of leg length (P<0.01), wattle
      length (P<0.05), and the combined relative asymmetry (P<0.05), the relative
      asymmetry of hens housed in deep litter being larger. There was no significant
      difference for the duration of tonic immobility between hens housed in deep
      litter or free range. Thus, hens with access to an outdoor area were less
      stressed than hens without access to an outdoor area, although the fearfulness
      was similar in both groups of birds. In experiment 2, cocks (n=120; 36 wk old)
      from 4 Spanish breeds, a synthetic breed, and the White Leghorn population, which
      had been housed in cages with or without a cold stress (0 to 10 degrees C) from
      24 wk of age, were used. Cold x breed interaction was significant for heterophil
      to-lymphocyte ratio (P<0.05), differences between cold-stressed and control birds
      being significant in 2 breeds. In these breeds (Red-Barred Vasca and Buff Prat),
      heterophil-to-lymphocyte ratio was significantly greater in cold-stressed birds.
      Cold stress effect was significant for the relative asymmetry of toe length
      (P<0.001) and the combined relative asymmetry (P<0.05), the relative asymmetry of
      birds with cold stress being larger than that of control birds. Thus, cold stress
      seriously negatively affects the welfare of cocks.

PMID- 18339982
TI  - Application of in-house mortality composting on viral inactivity of Newcastle
      disease virus.
AB  - This paper summarizes the results from 3 simulated in-house catastrophic
      mortality composting experiments. Experiment 1 evaluated the impact of water
      based foam mass depopulation on in-house composting of the carcasses and litter
      and showed that water-based foam improved windrow temperatures. Experiment 2
      evaluated the impact of freezing samples on virus recovery from windrow compost
      tissue and the choice of tissue for virus sampling within the bird. Experiment 2
      documented that freezing the samples had minimal impact on processing and that
      virus recovery was more consistent among inoculated breast meat than inoculated
      tracheas. Experiment 3 evaluated the impact of sawdust, straw, and sawdust-straw
      base layer litter material on in-house mortality composting. All litter materials
      were able to reach and maintain temperatures in excess of 60 degrees C for
      multiple days. No viral hemagglutination activity was observed after d 2 during
      any of the 3 experiments.

PMID- 18339983
TI  - Expression of inducible nitric oxide synthase in lungs of broiler chickens
      following intravenous cellulose microparticle injection.
AB  - Intravenous microparticle (MP) injection is a patented method used to select
      broilers with a robust pulmonary capacity and improved resistance to pulmonary
      hypertension syndrome (PHS, ascites). Injected MP become entrapped in the
      terminal pulmonary arterioles where they elicit an increase in pulmonary arterial
      pressure attributable to vascular occlusion and focal thrombocyte aggregation.
      Within 2 to 48 h postinjection perivascular mononuclear cell aggregates begin to
      form around MP-occluded vessels. Nitric oxide (NO) has been shown to modulate the
      pulmonary arterial pressure response to MP entrapment, but a role of NO during
      the more chronic (2 to 48 h) focal inflammatory response has not been evaluated.
      In this study we determined the time-course of inducible nitric oxide synthase
      (iNOS) expression in the lungs of MP-injected broilers from PHS-resistant (RES)
      and PHS-susceptible (SUS) lines. Four-week-old broilers (10 broilers/line per
      time point) were injected i.v. with a minimally lethal dose of MP, and the right
      lung was collected at 0 h (no MP) and 2, 24, and 48 h postinjection.
      Immunohistochemistry revealed that macrophage infiltration increased over time in
      both lines and was higher in the RES line than the SUS line (P<0.0001) at all
      time points. Nicotinamide adenine dinucleotide phosphate diaphorase staining
      showed nitric oxide synthase activity around MP-occluded vessels and in the
      perivascular mononuclear cell aggregates. Relative iNOS expression in lung tissue
      was examined by 2-step reverse transcription PCR. Lines differed in relative iNOS
      mRNA expression only at 24 h (P<0.001; RES > SUS line). For the RES line iNOS
      mRNA expression increased consistently from 0 to 48 h, but for the SUS line iNOS
      mRNA expression increased at 2 h, decreased to baseline at 24 h, and increased
      again by 48 h. The decline in iNOS expression in the SUS line between 2 and 24 h
      coincides with the interval when most of the MP-induced mortality occurs, which
      suggests that NO synthesized by iNOS may contribute to lower MP-induced mortality
      in the RES line when compared with the SUS line.

PMID- 18339984
TI  - Intratracheal administration of bacterial lipopolysaccharide elicits pulmonary
      hypertension in broilers with primed airways.
AB  - Broilers reared under commercial conditions inhale irritant gases and aerosolized
      particulates contaminated with gram-negative bacteria and bacterial
      lipopolysaccharide (LPS). Previous studies demonstrated that i.v. injections of
      LPS can trigger an increase in the pulmonary arterial pressure (PAP); however,
      the pulmonary hemodynamic response to aerosolized LPS entering via the most
      common route, the respiratory tract, had not been evaluated in broilers. In
      experiment 1, broilers reared on new wood shavings litter in clean environmental
      chambers either were not pretreated (control group) or were pretreated via
      aerosol inhalation of substances (food color dyes and propylene glycol) known to
      sensitize the airways. One day later, the broilers were anesthetized,
      catheterized to record the PAP, and an intratracheal aerosol spray of LPS (1 mL
      of 2 mg/mL of LPS) was administered. Broilers in the control group as well as
      broilers pretreated with aerosolized distilled water or yellow and blue food
      color dyes did not develop pulmonary hypertension (PH; an increase in PAP) after
      the intratracheal spray of LPS, whereas broilers that had been pretreated with
      red food color did develop PH in response to intratracheal LPS. In experiment 2,
      birds raised under commercial conditions on used wood shavings litter developed
      PH in response to intratracheal LPS regardless of whether they had been
      pretreated with aerosolized red food color dye. In experiment 3, broilers reared
      in clean environmental chambers on new wood shavings litter were used to
      demonstrate that Red Dye #3 and propylene glycol are capable of priming the
      responsiveness of the airways to a subsequent intratracheal LPS challenge. Common
      air contaminants such as LPS can result in PH leading to pulmonary hypertension
      syndrome (ascites) in broilers with appropriately primed airways.

PMID- 18339985
TI  - Effects of time-specific F-strain Mycoplasma gallisepticum inoculation overlays
      on prelay ts11-strain Mycoplasma gallisepticum inoculation on performance
      characteristics of commercial laying hens.
AB  - Mycoplasma bacteria are virtually ubiquitous in layer chicken flocks, and
      Mycoplasma gallisepticum is the species of greatest concern to commercial egg
      producers. Live M. gallisepticum vaccines were initially approved by the USDA for
      use in commercial layers in 1988 to help control M. gallisepticum outbreaks. In
      the present study, 2 trials were conducted to determine the effects of 2
      currently available live Mycoplasma vaccines (the ts11-and F-strains) when used
      together. The following 4 inoculation treatments were used: 1) sham inoculation
      at 10 wk of age, 2) ts11 at 10 wk, 3) ts11 at 10 wk overlaid by the F-strain at
      22 wk, and 4) ts11 at 10 wk overlaid by the F-strain at 45 wk. In each trial, at
      various ages between 18 and 57 wk of age, hen mortality; BW; egg weight; egg
      production; eggshell breaking strength; incidences of egg blood spots, egg meat
      spots, and eggshell pimpling; and eggshell weight per unit of surface area were
      assessed. The effects of inoculation treatment on egg weight at 27, 37, and 38 wk
      were inconsistent and variable. Eggshell pimpling and egg blood spot incidences
      at 56 wk were highest in eggs belonging to the ts11 at 10 wk/F-strain at 45 wk
      group. Despite increases in pimpling and blood spot incidences very late in
      production because of the ts11 at 10 wk/F-strain at 45 wk treatment, performance
      in layers was not adversely affected by a 10-wk ts11 inoculation alone or in
      conjunction with subsequent overlay inoculations of the F-strain during lay. It
      is therefore suggested that the 10-wk inoculation of commercial layers with ts11
      may reduce the negative impacts of a prelay F-strain inoculation on performance,
      as reported in earlier studies, while providing protection against subsequent
      field strain M. gallisepticum infections. Furthermore, the ts11- and F-strain M.
      gallisepticum treatment combinations may overcome some of the inadequacies that
      prelay ts11- or F-strain M. gallisepticum vaccines may have when given
      independently.

PMID- 18339986
TI  - Molecular subtype of infectious bronchitis virus in broiler flocks in Jordan.
AB  - Infectious bronchitis virus (IBV) causes respiratory disease in chickens all over
      the world. Infectious bronchitis virus has many serotypes that do not confer
      cross protection against each other. The current study was designed to know which
      IBV types were circulating in Jordanian broiler chickens. Tracheal swabs from 175
      broiler flocks at the acute phase of respiratory disease were collected. The
      swabs were subjected to RNA extraction and tested by reverse transcription PCR
      (RT-PCR). Specific-nested PCR were performed on RT-PCR products to detect and
      differentiate strains of Massachusetts, 4/91, and D274 types. The nucleic acid of
      IBV was detected in 105 out 174 (60%) broiler flocks by RT-PCR. Specific-nested
      PCR revealed that 35.2, 31.4, and 8.6% of these flocks had Massachusetts, 4/91,
      and D274, respectively, alone. In 24.8% of tested flocks, 2 types of IBV were
      detected. However, because the primers used in this study were designed
      specifically for 3 types of IBV, other types might have been present but not
      detected. Future work should include the isolation and molecular characterization
      of IBV in the region to adopt a suitable vaccination program using the common
      field serotypes as vaccines to protect against IBV-caused disease.

PMID- 18339987
TI  - The correlation of chemical and physical corn kernel traits with production
      performance in broiler chickens and laying hens.
AB  - A study was conducted to determine the influence on broiler chicken growth and
      laying hen performance of chemical and physical traits of corn kernels from
      different hybrids. A total of 720 male 1-d-old Ross-308 broiler chicks were
      allotted to floor pens in 2 replicated experiments with a randomized complete
      block design. A total of 240 fifty-two-week-old Hy-Line W-36 laying hens were
      allotted to cages in a randomized complete block design. Corn-soybean meal diets
      were formulated for 3 broiler growth phases and one 14-wk-long laying hen phase
      to be marginally deficient in Lys and TSAA to allow for the detection of
      differences or correlations attributable to corn kernel chemical or physical
      traits. The broiler chicken diets were also marginally deficient in Ca and
      nonphytate P. Within a phase, corn- and soybean-based diets containing equal
      amounts of 1 of 6 different corn hybrids were formulated. The corn hybrids were
      selected to vary widely in chemical and physical traits. Feed consumption and BW
      were recorded for broiler chickens every 2 wk from 0 to 6 wk of age. Egg
      production was recorded daily, and feed consumption and egg weights were recorded
      weekly for laying hens between 53 and 67 wk of age. Physical and chemical
      composition of kernels was correlated with performance measures by multivariate
      ANOVA. Chemical and physical kernel traits were weakly correlated with
      performance in broiler chickens from 0 to 2 wk of age (P<0.05, | r |<0.42).
      However, from 4 to 6 wk of age and 0 to 6 wk of age, only kernel chemical traits
      were correlated with broiler chicken performance (P<0.05, | r |<0.29). From 53 to
      67 wk of age, correlations were observed between both kernel physical and
      chemical traits and laying hen performance (P<0.05, | r |<0.34). In both
      experiments, the correlations of performance measures with individual kernel
      chemical and physical traits for any single kernel trait were not large enough to
      base corn hybrid selection on for feeding poultry.

PMID- 18339988
TI  - Influence of dietary electrolyte balance and microbial phytase on growth
      performance, nutrient utilization, and excreta quality of broiler chickens.
AB  - The possible interaction between dietary electrolyte balance (DEB=Na+K-Cl, mEq/kg
      of diet) and microbial phytase on the performance and nutrient utilization of
      broiler starters and litter quality was examined in this study. A 4 x 2 factorial
      arrangement of treatments was used with 4 levels of DEB (150, 225, 300, and 375
      mEq/kg of diet) and 2 levels of phytase (0 and 500 phytase units/kg of diet).
      Experimental diets were based on corn, soybean meal, and canola meal and were
      formulated to contain a nonphytate P level of 3 g/kg. The DEB levels were altered
      by the use of sodium bicarbonate and ammonium chloride. Each diet was offered to
      6 replicates of 8 birds each from d 1 to 21. Increasing the DEB values from 150
      to 300 mEq/kg had no effect (P>0.05) on the weight gains and feed per gain, but
      the gains were lowered (P<0.05) and the feed per gain was increased (P<0.05) at
      375 mEq/kg. Feed intake was unaffected (P>0.05) by DEB levels. Supplemental
      phytase improved (P<0.05) the weight gains and feed intake at all DEB levels.
      Feed per gain was lowered (P<0.05) by phytase addition, but a tendency for a DEB
      x phytate interaction (P=0.06) was also observed, indicating that the responses
      to phytase may be affected by DEB level. The responses in feed per gain were
      greater at the lowest DEB level, and phytase addition had no effect on feed per
      gain at the highest DEB level. Dietary electrolyte balance levels had no effect
      on the AME(n) and ileal N digestibility to 300 mEq/kg, but lowered (P<0.05) both
      criteria at 375 mEq/kg. Phytase addition improved (P<0.05) the AME(n) and ileal N
      digestibility. The improvements in AME(n) with 500 U/kg of phytase addition in
      150, 225, and 275 mEq/kg DEB were 53, 60, and 38 kcal/kg of DM, respectively. The
      main effect of DEB was significant (P<0.05) only for the ileal availability of Na
      and Cl, whereas added phytase influenced (P<0.05) the ileal availability of Ca,
      P, Na, K, and Cl. The effects of DEB were significant (P<0.05) for apparent ileal
      digestibility of all amino acids, except Ala (P=0.09), Arg, Met, and cystine. In
      general, the digestibilities of amino acids were unaffected when the DEB level
      was increased from 150 to 225 mEq/kg of diet, but decreased at the 300 and 375
      mEq/kg levels. Phytase addition improved (P<0.06 to 0.05) ileal digestibility of
      all amino acids, except Met and Tyr. Increasing DEB had adverse effects on
      excreta scores and DM content. Phytase addition, however, had no effect on
      excreta quality. The overall results of the present study suggest that
      variability in phytase responses in nutrient utilization may be explained, in
      part, by differences in dietary electrolyte levels.

PMID- 18339989
TI  - The effect of several organic acids on phytate phosphorus hydrolysis in broiler
      chicks.
AB  - Supplementation of some organic acids to a P-deficient diet has been shown to
      improve phytate P utilization. Two experiments were conducted from 0 to 16 d in
      battery brooders to determine the effect of various organic acids supplementation
      on phytate P utilization. In both experiments, birds were fed P-deficient corn
      and soybean meal-based diets. In experiment 1, citric acid, malic acid, fumaric
      acid, and EDTA were supplemented. Experiment 2 had a 2 x 2 factorial design with
      2 sources of Met, 2-hydroxy-4-(methylthio) butanoic acid (HMB) and dl-Met, with
      or without 500 U/kg of phytase. In experiment 1, the addition of citric, malic,
      and fumaric acids increased percentage of bone ash, but only the effect of citric
      acid was significant. The addition of citric and malic acids also significantly
      increased the retention of P and phytate P (P<0.05). In experiment 2, the
      addition of phytase to the diet significantly increased 16-d BW gain, feed
      intake, percentage of bone ash, milligrams of bone ash, phytate P disappearance,
      and decreased the incidence of P-deficiency rickets. Methionine source did not
      affect 16-d BW gain, feed intake, feed efficiency, milligrams of bone ash, or P
      rickets incidence. However, the birds fed HMB had a higher percentage of bone ash
      and phytate P disappearance compared with the groups fed dl-Met only when phytase
      was added to the diets. The additions of citric acid and HMB improved phytate P
      utilization. However, the reason why some organic acids are effective whereas
      others are not is not apparent.

PMID- 18339990
TI  - Metabolizable energy in different shea nut (Vitellaria paradoxa) meal samples for
      broiler chickens.
AB  - Shea nut meal is obtained after fat extraction from shea nuts produced in West
      Africa. Two experiments compared the ME of different shea nut meal samples. The
      objective of the first experiment was to estimate the TME(n) of 2 expeller shea
      nut meal samples and a single nonindustrial shea nut meal sample using a
      precision-fed broiler assay. The second objective was to compare the nutrient
      composition of 6 collected shea nut meal samples (i.e., 4 expeller, 2
      nonindustrial) as well as 2 defatted samples (1 expeller, 1 nonindustrial) and to
      examine the differences in AME between the samples. The 8 shea nut meal samples
      were fed at 3 dietary levels (0, 2, 4%) in a nutritionally complete basal diet to
      180 Ross male broiler chicks (12 to 20 d) in an AME assay. The mean TME(n) (3,577
      kcal/kg of DM) of expeller samples was higher (P<0.001) than TME(n) (3,017
      kcal/kg of DM) of the nonindustrial sample. The dietary level of shea nut meal
      had a significant (P<0.01) effect on AME with the 4% level tending to give a
      lower AME than the 0 or 2% levels. However, increasing levels of defatted shea
      nut meals from 2 to 4% had no effect on AME of the diets. It was concluded that
      the available energy concentrations in the shea nut meal samples were low
      relative to their nutrient compositions and variable due to the content and
      nature of the residual fat. The variation observed among samples indicates that
      industrial expeller shea nut meal samples are preferable to nonindustrial meals
      for use in poultry rations. The nutritional quality of shea nut meal still needs
      improvement to allow it to be a valuable feed ingredient.

PMID- 18339991
TI  - Phosphorus bioavailability, true metabolizable energy, and amino acid
      digestibilities of high protein corn distillers dried grains and dehydrated corn
      germ.
AB  - There is currently much ongoing research and interest for developing new
      processing technologies to produce corn distillers dried grains with solubles
      (DDGS). The current study evaluated a high protein (HP) distillers dried grains
      (DDG) and a dehydrated corn germ, which are products that can be produced by a
      modified dry milling process. Two chick experiments were conducted to determine
      the P bioavailability based on tibia ash. In addition, precision-fed rooster
      assays were conducted to determine TME(n) and amino acid digestibility. In the
      first chick assay, a P-deficient cornstarch-dextrose-soybean meal basal diet
      containing 0.10 to 0.13% nonphytate P was supplemented with 0.0, 0.05, and 0.10%
      P from KH(2)PO(4) or 7 and 14% conventional DDGS, HP DDG, and corn germ. In the
      second experiment, the P-deficient basal was supplemented with 7 and 14%
      conventional DDGS and 12.5 and 25% HP DDG. New Hampshire x Columbian female
      chicks were fed the experimental diets from 9 to 22 d posthatch, and
      bioavailability of P was estimated using the slope-ratio method where tibia ash
      was regressed on P intake. The total P content (90% DM basis) of the conventional
      DDGS, HP DDG, and corn germ were 0.76, 0.33, and 1.29%, respectively.
      Bioavailabilities of the P in conventional DDGS, HP DDG, and corn germ relative
      to KH(2)PO(4) were found to be 60, 56, and 25%, respectively. The TME(n) in
      conventional roosters was found to be significantly reduced for HP DDG and
      increased for the corn germ when compared with the conventional DDGS. The protein
      content (90% DM basis) of the HP DDG and corn germ was 33 and 14%, respectively,
      and the total lysine as a % of CP was approximately 2 times greater for the corn
      germ than for the HP DDG. Amino acid digestibilities in cecectomized roosters
      were consistently higher for the corn germ than for the HP DDG, which was similar
      to conventional DDGS.

PMID- 18339992
TI  - Comparison of various methods for endogenous ileal amino acid flow determination
      in broiler chickens.
AB  - The purpose of this study was to compare estimates of ileal endogenous amino acid
      (IEAA) losses determined in broiler chicks with a nitrogen-free diet (NFD), diets
      containing highly digestible proteins as intact casein or enzymatically
      hydrolyzed casein (EHC), and the regression method (RM). Male Ross 308 broiler
      chicks were fed a commercial starter diet from d 1 to 15 of age and the following
      test diets from d 15 to 21: NFD and diets containing 5, 10, or 15% casein or EHC
      as the sole protein source. All diets contained chromic oxide as a digestibility
      marker. Each diet was assigned to 6 replicate cages, with 10 birds each. On d 21,
      birds were euthanized to sample ileal digesta. Feeding increasing levels of EHC
      or casein linearly (P<0.0001) increased IEAA flow. Nonlinearity (P<0.05) was
      detected for Ile, Val, Glu, and Ser with EHC and for Met with casein. Compared
      with the NFD method, IEAA values extrapolated to zero EHC or casein intake were
      similar for all amino acids except Ile (200 vs. 321 mg/kg of DM intake), Val (270
      vs. 341 mg/ kg of DM intake), Ala (217 vs. 262 mg/kg of DM intake), and Ser (343
      vs. 577 mg/kg of DM intake), whose flows were higher with EHC (P<0.05). The
      present results show that IEAA values determined with the NFD, EHC, and casein
      diets, at different inclusion levels, were different for most amino acids and
      that, for all amino acids, the values obtained with NFD and RM involving feeding
      graded levels of casein or EHC were comparable. Thus, using IEAA values obtained
      with either the NFD or the RM to calculate standardized ileal amino acid
      digestibility coefficients will give similar values.

PMID- 18339993
TI  - An effective combination of carbohydrases that enables reduction of dietary
      protein in broilers: importance of hemicellulase.
AB  - After observing the effects of purified cellulase (C), hemicellulase (H),
      pectinase (P), and their combinations on the in vitro digestibility of a corn
      soybean meal broiler diet, we examined the associations between pectin breakdown
      and the digestibilities of CP and DM by using free galacturonic acid (GA) as an
      index of pectin breakdown. There was no significant effect of the single enzymes
      except for H. However, the enzyme combinations H + P, C + H, and C + H + P
      significantly increased CP and DM digestibilities, whereas the combination of C +
      P was not effective. Because H has activities of both H and P, these enzymes were
      considered to be important in stimulating digestion. Furthermore, when the
      enzymes increased CP and DM digestibilities, GA concentration was significantly
      higher, and clear correlations between CP and DM digestibilities and GA
      concentration were observed, whereas correlations between the digestibilities and
      concentration of glucose or xylose + mannose as indices of cellulose and
      hemicellulose breakdown, respectively, were not significant. From these
      observations, we hypothesized that a mixture of enzymes could increase the
      protein digestibility of broiler feed. Thus, in the in vivo experiment, low
      protein (19% CP) diets made mainly of corn and soybean meal with or without mixed
      enzymes were prepared and given to broiler chicks. The birds given the diet
      containing mixed enzymes showed significantly higher BW gain, with higher CP and
      DM digestibilities than the birds given the diet without the mixed enzymes.
      Moreover, the growth rate was same as that of the birds given the normal (21% CP)
      diet. The results indicate that the mixed enzyme preparation can effectively
      degrade indigestible cell constituents and thus enable the protein of the broiler
      feed to become more digestible. Furthermore, the results indicate the importance
      of H as a rate-limiting factor of cell wall breakdown.

PMID- 18339994
TI  - Nutritional and physiological effects of dietary sinapic acid (4-hydroxy-3,5
      dimethoxy-cinnamic acid) in broiler chickens and its metabolism in the digestive
      tract.
AB  - Sinapic acid (SA) is a major free phenolic acid in rapeseed meal, with the
      majority found in the esterified form of sinapine. Two experiments were conducted
      to delineate the effect of dietary SA on broiler chickens, in terms of
      performance, toxicity, and nutrient digestibility. In the first experiment, 80
      male broiler chicks were randomly assigned to 5 diets adequate in all nutrients
      and containing 0, 0.05, 0.10, 0.15, or 0.20% dietary SA. Performance from 0 to 18
      d of age and the relative size of all the internal organs and intestines were not
      affected (all P>0.05) by dietary treatment. In addition, dietary SA had no effect
      (P>0.05) on the serum activity of creatine kinase and lactate dehydrogenase,
      which indicated that there was no damage to skeletal muscle, heart muscle, liver,
      kidneys, or brain. The objectives of the second experiment were to investigate
      the effect of SA on nutrient retention and to study the retention of SA in the
      digestive tract. Male broiler chicks (96) were randomly assigned into 4
      treatments containing dietary SA at 0, 0.025, 0.05, and 0.10%. Dietary SA at the
      0.025% level increased feed intake compared with control (P<0.05). Regression
      analysis indicated a quadratic response for both weight gain and feed intake
      (P<0.05) as SA increased in the diet. Again, dietary SA did not affect the
      relative weights of bursa of Fabricius, liver, kidney, or digestive tract.
      Nitrogen-corrected AME and protein digestibility were not affected by SA level. A
      negative linear relationship was found between dietary SA level and apparent
      ileal digestibility of Met, Thr, Ser, Pro, Gly, Ala, and Phe. Sinapic acid
      disappearance in the ileum was above 97% for all SA levels, whereas apparent SA
      retention in excreta ranged from 64 to 79%. Sinapic acid at dietary levels
      investigated in this research is apparently not toxic to broiler chickens but may
      have a negative effect on amino acid digestibility at higher levels.

PMID- 18339995
TI  - Aflatoxicosis in chickens (Gallus gallus): an example of hormesis?
AB  - Poultry has commonly been considered highly susceptible to aflatoxins. However,
      among domestic fowl there is wide variability in specific species sensitivity to
      these mycotoxins. Comparative toxicological studies in avian species have shown
      that ducklings and turkey poults are the most sensitive species to aflatoxins,
      quails show intermediate sensitivity, whereas chickens are the most resistant.
      Hormesis is a dose-response phenomenon characterized by low-dose stimulation and
      high-dose inhibition. The low-dose stimulation is typically maximal at only about
      30 to 60% greater than controls. Hormesis has been noted in regards to changes in
      body weight in numerous studies, including those performed for the US National
      Toxicology Program, with over 50 chemicals. The present paper assesses how
      relatively low levels of aflatoxin consumption in feed may affect the growth rate
      of chickens. In general, multiple independent investigations have shown that such
      aflatoxin consumption affects growth in a hormetic-like biphasic manner with a
      low dose stimulation and a high dose inhibition. Such observations were then
      generalized to other toxic agents and animal models, suggesting that low doses of
      stressor agents induce adaptive responses as reflected in accelerated growth
      rates. The implications of such hormetic dose responses are briefly discussed.

PMID- 18339996
TI  - Effect of dietary dehydrated pasture and citrus pulp on the performance and meat
      quality of broiler chickens.
AB  - Some feedstuffs containing significant levels of fiber may be a good source of
      bioactive compounds that may contribute to improving broiler meat quality.
      However, high fiber level can have a negative impact on broiler performance. A
      study was undertaken to investigate the impact of incorporating citrus pulp (5 or
      10%) or dehydrated pasture (5 or 10%) on the performance, carcass yield, and
      characteristics of broiler chickens. A diet containing neither citrus pulp nor
      dehydrated pasture was used as control. The results on growth performances showed
      that daily weight gain was reduced by 26% in birds of the 10% citrus pulp
      treatment (P<0.05). Compared with the control treatment, increases in feed intake
      occurred in birds consuming diets with 5 or 10% citrus pulp, which resulted in
      significantly higher feed conversion rates with the 10% level. Under the same
      incorporation rate, dehydrated pasture had effects less evident on the
      performances of broiler chicken. In addition, diets containing citrus pulp,
      displaying higher percentages of soluble nonstarch polysaccharides, increased
      small intestine relative length, and reduced carcass yield. Inclusion of 10%
      dehydrated pasture in diets resulted in improved breast skin yellowness (P<0.05).
      Finally, the results revealed that incorporation of the nonstarch polysaccharide
      rich feedstuffs had a major impact on the fatty acid profile (affected 16 of 21
      fatty acids) of broiler meat. Polyunsaturated fatty acids content in meat was
      higher in birds consuming the highest levels of both citrus pulp and dehydrated
      pasture, leading to increased ratios of polyunsaturated to saturated fatty acids.
      Together, the results suggest that incorporation of moderate levels of dehydrated
      pastures in poultry diets has a minor impact on broiler performance and can
      contribute significantly to improve breast skin yellowness and fatty acid
      composition of meat.

PMID- 18339997
TI  - Ideal ratios of isoleucine, methionine, methionine plus cystine, threonine,
      tryptophan, and valine relative to lysine for white leghorn-type laying hens of
      twenty-eight to thirty-four weeks of age.
AB  - Seven separate experiments were conducted with Hy-Line W-36 hens to determine the
      ideal ratio of Arg, Ile, Met, Met+Cys, Thr, Trp, and Val relative to Lys for
      maximal egg mass. The experiments were conducted simultaneously and were each
      designed as a randomized complete block design with 60 experimental units (each
      consisting of 1 cage with 2 hens) and 5 dietary treatments. The 35 assay diets
      were made from a common basal diet (2,987 kcal/kg of ME; 12.3% CP; 4.06% Ca,
      0.47% nonphytate P), formulated using corn, soybean meal, and meat and bone meal.
      The true digestible amino acid contents in the basal diet were determined using
      the precision-fed assay with adult cecectomized roosters. Crystalline L-Arg (free
      base), L-Ile, L-Lys.HCl, DL-Met, L-Thr, L-Trp, and L-Val (considered 100% true
      digestible) were added to the basal diet at the expense of cornstarch to make the
      respective assayed amino acid first limiting and to yield 5 graded inclusions of
      the assayed amino acid. Hens were fed the assay diets from 26 to 34 wk of age,
      with the first 2 wk considered a depletion period. Egg production was recorded
      daily and egg weight was determined weekly on eggs collected over 48 h; egg mass
      was calculated as egg production x egg weight. The requirement for each amino
      acid was determined using the broken-line regression method. Consumption of Arg
      did not affect egg mass, thus a requirement could not be determined. The true
      digestible amino acid requirements used to calculate the ideal amino acid ratio
      for maximum egg mass were 426 mg/d of Ile, 538 mg/d of Lys, 253 mg/d of Met, 506
      mg/d of Met+Cys, 414 mg/d of Thr, 120 mg/d of Trp, and 501 mg/d of Val. The ideal
      amino acid ratio for maximum egg mass was Ile 79%, Met 47%, Met+Cys 94%, Thr 77%,
      Trp 22%, and Val 93% on a true digestible basis relative to Lys. The ideal Met
      and Met+Cys ratios were verified in an ensuing identical experiment with 52- to
      58-wk-old hens.

PMID- 18339998
TI  - Effect of wheat cultivar and enzyme addition to broiler chicken diets on nutrient
      digestibility, performance, and apparent metabolizable energy content.
AB  - A total of 5,000 one-day-old male broiler chickens were assigned to 8 different
      treatments in a 4 x 2 factorial design. Four wheat cultivars (Amiro, Guadalupe,
      Isengrain, and Horzal) and 2 levels (0 or 1 kg/t of feed) of an enzyme cocktail
      (Avizyme 1300, xylanase, 2,500 U/kg and protease, 800 U/kg) were used.
      Nutritionally complete mash diets contained 65 and 70% of the test wheat for the
      starter and grower period, respectively. Test wheats were used in diets for
      broilers, and growth performance and AME contents were measured. Broiler
      performance was measured in 4,800 broilers allocated to floor pens with 75 birds
      each and fed from 1 to 42 d of age. Digestibilities and AME contents of diets
      were measured in 200 broilers from 6 to 27 d of age individually allocated to
      battery cages. Chromic oxide (Cr(2)O(3)) at an inclusion rate of 0.5% in the diet
      was used as an indigestible marker. Apparent metabolizable energy was corrected
      by zero N balance to obtain AME(n). Wheat cultivar strongly influenced animal
      performance during the starter period (1 to 21 d of age). During the grower
      period (21 to 42 d of age), only BW and daily feed intake were influenced by
      wheat cultivar. Differences in daily feed intake were associated with differences
      in AME(n) intake during the starter period, but not during the grower period.
      Nutrient digestibility was higher with the use of enzyme. Animal performance was
      not affected (i.e., wheat cultivar differences were not eliminated by using
      enzymes). During the grower period, significant interactions were detected with
      regard to nutrient digestibility and AME(n). Differences in AME(n) content of
      wheat could not be explained by digestible starch.

PMID- 18339999
TI  - Cloning, sequencing, characterization, and expressions of divalent metal
      transporter one in the small intestine of broilers.
AB  - Divalent metal transporter 1 (DMT1) is an electrogenic transporter of divalent Mn
      that is expressed at a high level on the brush-border membrane of enterocytes.
      This study is the first reported isolation of the 2 full-length cDNA sequences of
      the small intestinal DMT1 gene of broilers by rapid amplification of cDNA ends.
      The chicken DMT1 isoform I cDNA was 1,972 bp and contained a 1,695-bp open
      reading frame encoding a 564-amino acid protein, and the chicken DMT1 isoform II
      cDNA was 1,775 bp and contained a 1,593-bp open reading frame encoding a 530
      amino acid protein. The 2 chicken DMT1 isoform transcripts differed in their 3'
      translated regions and untranslated regions. The identities of the amino acid
      sequence deduced from the full-length cDNA sequence of the chicken DMT1 isoform I
      with DMT1 not containing the iron-responsive element of the mouse, rat, and human
      were 82, 82, and 80%, respectively. The identities of the amino acid sequence
      deduced from the full-length cDNA sequence of the chicken DMT1 isoform II with
      those of the mouse, rat, and human were 84, 84, and 83%, respectively. Analyses
      of hydrophobicity, transmembrane region, and signal peptides of DMT1 proteins
      deduced by nucleotide sequences suggested that chicken DMT1 isoforms are
      transmembrane proteins with several conserved peptide sequences, such as N-linked
      glycosylation signals (N-X-S/ T, where X designates any amino acid) and the
      consensus transport motif. The total mRNA levels of the 2 chicken DMT1 isoforms,
      the mRNA levels of chicken DMT1 isoform I, and the mRNA levels of chicken DMT1
      isoform II in the duodenum and jejunum were higher (P<0.002) than that in the
      ileum by real-time reverse transcription PCR assay. There was no significant
      difference (P>0.26) between the duodenum and jejunum for the above 3 indices. The
      mRNA level of the chicken DMT1 isoform I was higher (P<0.001) than that of the
      chicken DMT1 isoform II in each small intestinal segment of Mn-deficient
      broilers.

PMID- 18340000
TI  - Recombinant avian adeno-associated virus-mediated oviduct-specific expression of
      recombinant human tissue kallikrein.
AB  - Human tissue kallikrein (hK1) plays an important role in regulation of blood
      pressure, electrolyte and glucose transport, and renal function. To evaluate the
      feasibility of viral vector-mediated expression of recombinant human tissue
      kallikrein (rhK1) in the egg white of laying hens, human tissue kallikrein gene
      (hKLK1) cDNA-expression cassette was subcloned into avian adeno-associated virus
      (AAAV) transfer vector pAITR and transfected into AAV-293 cells with AAAV helper
      vector pcDNA-ARC and adenovirus helper vector pHelper. The recombinant viral
      particles with a typical AAAV morphology and relatively high titer were generated
      and identified by PCR and electron microscopy. After 1 intravenous injection of
      each laying hen with 2 x 10(10) viral particles, oviduct-specific expression of
      hKLK1 cDNA was demonstrated by reverse transcription-PCR. Secretion of rhK1 into
      the egg white was detected by enzymatic assay from d 2, reaching the highest
      level of 107 U/mL in wk 3, and lasted for more than 6 wk after injection. Western
      blotting showed that the oviduct-expressed rhK1 had the same molecular mass with
      the natural enzyme. These data suggest that rAAAV can mediate high level and long
      lasting transgene expression in oviduct cells, and the established expression
      system is useful for production of other recombinant proteins.

PMID- 18340001
TI  - Effects of dietary inulin on the intestinal short chain fatty acids and microbial
      ecology in broiler chickens as revealed by denaturing gradient gel
      electrophoresis.
AB  - Inulin can stimulate the growth of the intestinal bacteria as well as alter the
      ratio among various short chain fatty acids (SCFA) produced. In the present
      study, we analyzed the effect of dietary inulin on the intestinal bacterial
      community as determined by denaturing gradient gel electrophoresis analysis of
      universal 16S rDNA after amplication with PCR and SCFA profile. Broilers were fed
      a diet primarily composed of corn-soybean meal or same diet with 1% inulin for 42
      d. The relative weight of digesta-filled ceca of the inulin-fed group was higher
      (P<0.01) than in the control group. Amongst SCFA, only acetate could be detected
      in the jejunal digesta, which tended to be higher (P=0.09) in inulin-fed group
      compared with the control group. Inulin did not affect the total concentration of
      SCFA in the cecal digesta. The relative proportion of n-butyrate was elevated
      (P=0.05) with a concomitant decrease in the concentration of n-valerate (P<0.05)
      in the inulin-fed group compared with the control group. Dietary inulin did not
      affect the number of PCR-denaturing gradient gel electrophoresis bands nor their
      diversity in the jejunal and cecal digesta. Intragroup similarities were not
      different between the groups, nor were any differences between intra-and
      intergroup similarities in the jejunal and cecal samples. In conclusion, inulin
      altered the cecal microbial metabolic activity without any major impact on the
      composition of intestinal bacterial communities as measured by the present
      techniques.

PMID- 18340002
TI  - Turkey sperm reside in the tubular glands in the urodeum following artificial
      insemination.
AB  - A turkey hen in egg production requires 48 h after the last insemination to
      maximize the number of sperm in the uterovaginal junction sperm-storage tubules.
      Where the sperm that continue to fill the oviductal sperm-storage sites during
      this 48-h period reside remains unknown. Histological sections of the juncture of
      the vagina with the urodeum, the central compartment of the cloaca, revealed deep
      tubular glands containing periodic acid-Schiff-positive secretory material. When
      examined 36 h after the last artificial insemination, sperm were observed in the
      lumen of the tubular glands associated with the urodeum. We suggest that sperm
      reside in the tubular glands within the urodeum and are released in association
      with the secretory activity of the tubular glands. These sperm then may ascend
      the vagina to continue to populate the sperm-storage tubules. Alternatively, the
      sperm in the tubular glands of the urodeum may be evidence of spermatorrhea and
      have no functional role in the fertilization process.

PMID- 18340003
TI  - Microbial growth on broiler carcasses stored at different temperatures after air-
      or water-chilling.
AB  - Poultry meat has a high risk of contamination during its processing. Storage
      temperature, type of packaging, and types and numbers of psychrotrophic bacteria
      are the major factors determining the spoilage of poultry meat. Before packaging,
      poultry carcasses are chilled by air or water currents in commercial
      slaughterhouses. The packaging material and methods are other factors influencing
      the spoilage of poultry meat. Although unpackaged carcasses had lower production
      costs, they were found to contain high numbers of microorganisms. The unpackaged
      carcasses are often not recommended for food safety and public health risks. The
      present study examines the growth of some spoilage microorganisms on unpackaged
      carcasses and on broiler carcasses packaged in polyethylene bags or synthetic
      plates. The carcasses examined in this study were collected from the
      slaughterhouses of the Bolu region of Turkey. All carcasses were subjected to an
      air or water chilling process in the slaughterhouse and then stored at 0, 4, or 7
      degrees C for 14 d. Samples were taken on d 0, 4, 8, 10, and 14 of storage and
      analyzed for total bacterial count, and for Pseudomonas spp., Enterobacteriaceae,
      yeasts, and molds. The carcasses packaged in synthetic plates or polyethylene
      bags and kept at 0 degrees C were microbiologically safer and had longer shelf
      life, so they are found to be the most reliable for consuming. The shelf life of
      broiler carcasses could be further increased by improving hygiene and sanitation
      procedures at the slaughterhouse.

PMID- 18340004
TI  - Caprylic acid supplemented in feed reduces enteric Campylobacter jejuni
      colonization in ten-day-old broiler chickens.
AB  - Campylobacter is one of the leading causes of human foodborne illness in the
      United States, and epidemiological evidence indicates that poultry and poultry
      products are a significant source of human Campylobacter infections. Reducing
      Campylobacter in the intestinal tract would reduce contamination of poultry
      products and eggs. Caprylic acid, an 8-carbon medium-chain fatty acid has been
      shown to be bactericidal against several pathogenic bacteria. It has, however,
      not been tested in the control of Campylobacter in chickens. Four trials were
      carried out to evaluate the efficacy of caprylic acid against cecal Campylobacter
      jejuni colonization in 10-d-old chicks. In the first 2 trials, day-of-hatch
      chicks (n=40 per trial) were assigned to negative controls (no Campylobacter, no
      caprylic acid), positive controls (Campylobacter, no caprylic acid), and a low
      (0.7%) and a high (1.4%) dose of caprylic acid supplemented in regular chick
      starter feed (n=10 chicks/treatment). Two more trials were carried out to
      evaluate a wider range of caprylic acid doses on cecal Campylobacter counts, in
      which day-of-hatch chicks (n=90 per trial) were assigned to 9 treatments:
      negative controls (no Campylobacter, no caprylic acid) and caprylic acid doses of
      0 (positive controls), 0.35, 0.525, 0.7, 0.875, 1.05, 1.225, and 1.4% (n=10
      chicks/treatment). Except for the negative controls, chicks were orally gavaged
      with approximately 1 x 10(6) cfu Campylobacter on d 3. On d 10, cecal contents
      were collected and Campylobacter concentrations were determined in each trial. In
      all 4 trials, the 0.7% dose of caprylic acid consistently reduced Campylobacter
      content counts compared with the positive control. In trials 3 and 4, doses less
      than 1.05% consistently reduced cecal Campylobacter content in both trials. At
      the higher doses, caprylic acid reduced feed consumption and body weight, but did
      not affect feed conversion when compared with the positive controls. These data
      suggest that low-dose supplementation with caprylic acid in feed may reduce
      Campylobacter colonization in young chickens.

PMID- 18340005
TI  - Feeding broiler breeder males. 4. Deficient feed allocation reduces fertility and
      broiler progeny body weight.
AB  - Two experiments were conducted to evaluate the effects of male broiler breeder
      feed intake on broiler progeny performance. In experiment 1, a low cumulative
      nutrition program supplied 29,580 kcal of ME and 1,470 g of CP, whereas a high
      cumulative nutrition program supplied 33,500 kcal of ME and 1,730 g of CP to
      photostimulation at 21 wk of age. Two diets (HiDiet and LoDiet) were formulated,
      and a single feeding program was used to achieve the selected nutrient intakes.
      The HiDiet group of males in experiment 1 achieved greater BW and exhibited lower
      fertility when fed as the LoDiet males from the onset of egg production. The
      HiDiet breeder males subsequently produced male broilers from eggs laid at 29 wk
      of age that exhibited lower BW at 42 d. This was due to the heaviest 50% of the
      breeder males in this treatment not gaining BW consistently due to less-than
      adequate ME intake relative to their greater BW requirements. Two feeding
      programs during the production period (constant or increasing) were compared in
      experiment 2. Broilers were hatched from eggs laid at 32 and 48 wk of age to
      evaluate the vertical effect of male treatments on progeny performance. No
      difference in fertility or broiler performance was found at 32 wk. However, the
      constant feeding program produced lower fertility from 36 to 55 wk of age, and
      this resulted in a lower male and female broiler progeny BW at 42 d of age from
      eggs collected at 48 wk of age. Adequate breeder male feed allocation during the
      production period improved fertility and favorably affected broiler progeny
      performance in both experiments. However, broiler progeny effects were observed
      only when there were differences in fertility, which suggests that the males with
      the greatest genetic potential were not mating at these times.

PMID- 18340006
TI  - Cytochrome P450 2C9-induced angiogenesis is dependent on EphB4.
AB  - OBJECTIVE: Cytochrome P450 (CYP) epoxygenase-derived epoxyeicosatrienoic acids
      (EETs) are known to stimulate angiogenesis, but the mechanisms involved are
      incompletely understood. Because EphB4 is involved in vascular development, the
      aim of this study was to investigate whether, and to what extent, EphB4 is part
      of the signaling cascade that results in CYP2C9-mediated angiogenesis. METHODS
      AND RESULTS: CYP2C9 overexpression as well as stimulation with 11,12-EET (up to
      48 hours) time-dependently increased EphB4 expression in endothelial cells. This
      effect and the activation of the EphB4 promoter were mediated by the
      phosphatidylinositol-3-kinase (P13-K)/Akt pathway and sensitive to the P13-K
      inhibitor LY 294002 as well as to simultaneous transfection with dominant
      negative Akt. 11,12-EET treatment also increased EphB4 expression in isolated
      mouse mesenteric arteries as well as in the vessels that developed in 11,12-EET
      impregnated Matrigel plugs. Moreover, the CYP2C9-stimulated formation of
      capillary-like structures in a modified spheroid assay was markedly attenuated by
      EphB4 downregulation (antisense oligonucleotides). Using a parallel approach in
      vivo, the inclusion of siRNA directed against EphB4 in EET-impregnated Matrigel
      plugs prevented endothelial cell invasion and vascularization. CONCLUSIONS: Our
      data indicate that EphB4 is a critical component of the CYP2C9- and 11,12-EET
      activated signaling cascade that promotes angiogenesis in vitro as well as in
      vivo.

PMID- 18340007
TI  - Association of stearoyl-CoA desaturase 1 activity with familial combined
      hyperlipidemia.
AB  - OBJECTIVE: Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme involved
      in the synthesis of monounsaturated fatty acids, and in mice SCD1 activity is
      associated with plasma triglyceride levels. We used the fatty acid desaturation
      index (the plasma ratio of 18:1/18:0) as a marker of SCD1 activity to investigate
      the relationship of SCD1 to familial combined hyperlipidemia (FCHL). METHODS AND
      RESULTS: The fatty acid desaturation index was measured in 400 individuals from
      18 extended FCHL pedigrees. FCHL-affected individuals exhibited increased SCD1
      activity when compared to unrelated controls (P < 0.0001). The fatty acid
      desaturation index was found to be highly heritable (h(2) = 0.48, P = 2.2 x 10(
      11)) in this study sample. QTL analysis in 346 sibling pairs from 18 FCHL
      families revealed suggestive linkage of the desaturation index to chromosomes
      3p26.1 to 3p13 (z = 2.7, P = 0.003), containing the peroxisome proliferator
      activated receptor gamma (PPARgamma) gene, and 20p11.21 to 20q13.32 (z = 1.7, P =
      0.04), containing the hepatocyte nuclear factor 4, alpha (HNF4alpha) gene. A
      specific haplotype of HNF4alpha was found to be associated with the desaturation
      index in these FCHL families (P = 0.002). CONCLUSIONS: Our results demonstrate
      that the fatty acid desaturation index is a highly heritable trait that is
      associated with the dyslipidemia observed in FCHL.

PMID- 18340008
TI  - Suppression of the Raf/MEK/ERK signaling cascade and inhibition of angiogenesis
      by the carboxyl terminus of angiopoietin-like protein 4.
AB  - OBJECTIVE: Angiopoietin-like protein 4 (Angptl4) is a secreted glycoprotein that
      has recently been implicated in the regulation of angiogenesis and metastasis.
      This study aimed to investigate the structural and cellular basis underlying the
      biological actions of Angptl4. METHODS AND RESULTS: Circulating Angptl4 was
      proteolytically cleaved into NH2-terminal coiled-coil domain (N-Angptl4) and COOH
      terminal fibrinogen-like domain (C-Angptl4). Using amino acid sequencing
      analysis, we identified a major cleavage site between Lys(168) and Leu(169) and a
      minor cleavage site between Lys(170) and Met(171) in mouse Angptl4. C-Angptl4,
      but not N-Angptl4, potently inhibited both bFGF- and VEGF-induced cell
      proliferation, migration, and tubule formation in endothelial cells, and
      prevented neovascularization in mice. Treatment of C-Angptl4 with PNGase F (an N
      glycosidase) ablated its N-linked glycosylation, and also significantly
      attenuated its antiangiogenic activities. C-Angptl4 blocked bFGF-induced
      activation of ERK1/2 MAP kinase, but had no obvious effect on Akt and P38 MAP
      kinase. Furthermore, C-Angptl4 abrogated bFGF-induced phosphorylation of Raf-1
      and MEK1/2, whereas neither auto-phosphorylation of FGF receptor-1 nor activation
      of Ras was affected, suggesting that the blockage occurs at the level of Raf-1
      activation. CONCLUSIONS: The carboxyl terminus of Angptl4 alone is sufficient to
      suppress angiogenesis, possibly through inhibiting the Raf/MEK/ERK1/2 MAP kinase
      pathway in endothelial cells.

PMID- 18340009
TI  - Cholesterol synthesis inhibition elicits an integrated molecular response in
      human livers including decreased ACAT2.
AB  - OBJECTIVE: The purpose of this study was to identify how different degrees of
      cholesterol synthesis inhibition affect human hepatic cholesterol metabolism.
      METHODS AND RESULTS: Thirty-seven normocholesterolemic gallstone patients
      randomized to treatment with placebo, 20 mg/d fluvastatin, or 80 mg/d
      atorvastatin for 4 weeks were studied. Based on serum lathosterol determinations,
      cholesterol synthesis was reduced by 42% and 70% in the 2 groups receiving
      statins. VLDL cholesterol was reduced by 20% and 55%. During gallstone surgery, a
      liver biopsy was obtained and hepatic protein and mRNA expression of rate
      limiting steps in cholesterol metabolism were assayed and related to serum
      lipoproteins. A marked induction of LDL receptors and 3-hydroxy-3-methylglutaryl
      (HMG) coenzyme A (CoA) reductase was positively related to the degree of
      cholesterol synthesis inhibition (ChSI). The activity, protein, and mRNA for
      ACAT2 were all reduced during ChSI, as was apoE mRNA. The lowering of HDL
      cholesterol in response to high ChSI could not be explained by altered expression
      of the HDL receptor CLA-1, ABCA1, or apoA-I. CONCLUSIONS: Statin treatment
      reduces ACAT2 activity in human liver and this effect, in combination with a
      reduced Apo E expression, may contribute to the favorable lowering of VLDL
      cholesterol seen in addition to the LDL lowering during statin treatment.

PMID- 18340010
TI  - Combined deficiency of dystrophin and beta1 integrin in the cardiac myocyte
      causes myocardial dysfunction, fibrosis and calcification.
AB  - The dystrophin-glycoprotein complex is a large complex of membrane-associated
      proteins linking the cytoskeleton to the extracellular matrix in muscle.
      Transmembrane heterodimeric (alphabeta) integrins serve also as cellular adhesion
      molecules and mechanotransducers. In the animal model for Duchenne muscular
      dystrophy, the mdx mouse, loss of dystrophin causes more severe abnormalities in
      skeletal than in cardiac muscle. We hypothesized that ablation of cardiac myocyte
      integrins in the mdx background would lead to a severe cardiomyopathic phenotype.
      Mdx mice were crossed to ones with cardiac myocyte-specific deletion of beta1
      integrin (beta1KO) to generate beta1KOmdx. Unstressed beta1KOmdx mice were viable
      and had normal cardiac function; however, high mortality was seen in peri- and
      postpartum females by 6 months of age, when severe myocardial necrosis and
      fibrosis and extensive dystrophic calcification was seen. Decreased ventricular
      function and blunted adrenergic responsiveness was found in the beta1KOmdx mice
      compared with control (Lox/Lox, no Cre), beta1KO, and mdx. Similarly, adult
      beta1KOmdx males were more prone to isoproterenol-induced heart failure and death
      compared with control groups. Given the extensive calcification, we analyzed
      transcript levels of genes linked to fibrosis and calcification and found matrix
      gamma-carboxyglutamic acid protein, decorin, periostin, and the osteoblast
      transcription factor Runx2/Cbfa1 significantly increased in beta1KOmdx cardiac
      muscle. Our data show that combined deficiency of dystrophin and integrins in
      murine cardiac myocytes results in more severe cardiomyopathic changes in the
      stressed myocardium than reduction of either dystrophin or integrins alone and
      predisposes to myocardial calcification.

PMID- 18340011
TI  - Targeted deletion of PTEN in smooth muscle cells results in vascular remodeling
      and recruitment of progenitor cells through induction of stromal cell-derived
      factor-1alpha.
AB  - We previously showed that changes in vascular smooth muscle cell (SMC) PTEN/Akt
      signaling following vascular injury are associated with increased SMC
      proliferation and neointima formation. In this report, we used a genetic model to
      deplete PTEN specifically in SMCs by crossing PTEN(LoxP/LoxP) mice to mice
      expressing Cre recombinase under the control of the SM22alpha promoter. PTEN was
      downregulated with increases in phosphorylated Akt in major vessels, hearts, and
      lungs of mutant mice. SMC PTEN depletion promoted widespread medial SMC
      hyperplasia, vascular remodeling, and histopathology consistent with pulmonary
      hypertension. Increased vascular deposition of the chemokine stromal cell-derived
      factor (SDF)-1alpha and medial and intimal cells coexpressing SM-alpha-actin and
      CXCR4, the SDF-1alpha receptor, was detected in SMC PTEN-depleted mice. PTEN
      deficiency in cultured aortic SMCs induced autocrine growth through increased
      production of SDF-1alpha. Blocking SDF-1alpha attenuated autocrine growth and
      blocked growth of control SMCs induced by conditioned media from PTEN-deficient
      SMCs. In addition, SMC PTEN deficiency enhanced progenitor cell migration toward
      SMCs through increased SDF-1alpha production. SDF-1alpha production by other cell
      types is regulated by the transcription factor hypoxia-inducible factor (HIF)
      1alpha. We found SMC nuclear HIF-1alpha expression in PTEN-depleted mice and
      increased nuclear HIF-1alpha in PTEN-deficient SMCs. Small interfering RNA
      mediated downregulation of HIF-1alpha reversed SDF-1alpha induction by PTEN
      depletion and inhibition of phosphatidylinositol 3-kinase signaling blocked HIF
      1alpha and SDF-1alpha upregulation induced by PTEN depletion. Our data show that
      SMC PTEN inactivation establishes an autocrine growth loop and increases
      progenitor cell recruitment through a HIF-1alpha-mediated SDF-1alpha/CXCR4 axis,
      thus identifying PTEN as a target for the inhibition of pathological vascular
      remodeling.

PMID- 18340012
TI  - Calcium dynamics and ventricular fibrillation.

PMID- 18340013
TI  - A vascular bone collector: arterial calcification requires tissue-type
      transglutaminase.

PMID- 18340014
TI  - Physics meets molecules: is modulation of shear stress the link to vascular
      prevention?

PMID- 18340015
TI  - Myocardial-coronary interactions: against the canon.

PMID- 18340016
TI  - Cardiac myosin light chain kinase: a new player in the regulation of myosin light
      chain in the heart.

PMID- 18340018
TI  - Reduced glucocorticoid production rate, decreased 5alpha-reductase activity, and
      adipose tissue insulin sensitization after weight loss.
AB  - OBJECTIVE: The epidemics of obesity, insulin resistance, and type 2 diabetes have
      heightened the need to understand mechanisms that contribute to their
      pathogenesis. Increased endogenous glucocorticoid production has been implicated
      based on parallels with Cushing's syndrome. We have assessed the impact of weight
      loss on glucocorticoid secretion and metabolism (notably 11beta-hydroxysteroid
      dehydrogenase type 1 and 5alpha-reductase [5alphaR] activity) and insulin
      sensitivity. RESEARCH DESIGN AND METHODS: Twenty obese volunteers were
      investigated before and after weight loss. Patients underwent hyperinsulinemic
      euglycemic clamps with simultaneous adipose microdialysis and oral cortisone
      acetate administration. Changes in glucocorticoid secretion and metabolism were
      assessed using 24-h urine collections. RESULTS: Before weight loss, fat mass
      correlated with glucocorticoid secretion rate (total fat, r = 0.46, P < 0.05;
      trunk fat, r = 0.52, P < 0.05); however, glucocorticoid secretion rate was
      inversely related to insulin sensitivity (r = -0.51, P < 0.05). Hyperinsulinemia
      failed to suppress adipose tissue interstitial fluid glycerol release (180 +/- 50
      micromol [basal] vs. 153 +/- 10 micromol [steady state], NS). After oral
      cortisone (25 mg), cortisol concentrations within adipose interstitial fluid
      increased (4.3 +/- 1.1 vs. 14.2 +/- 2.6 nmol/l, P < 0.01), but glycerol
      concentrations did not change. After weight loss, insulin sensitivity increased.
      Consistent with insulin sensitization, adipose tissue interstitial fluid glycerol
      concentrations fell under hyperinsulinemic conditions (186 +/- 16 vs. 117 +/- 9
      micromol, P < 0.05). Glucocorticoid secretion decreased (11,751 +/- 1,520 vs.
      7,464 +/- 937 microg/24 h, P < 0.05) as did 5alphaR activity (5alpha
      tetrahydrocortisol-to-tetrahydrocortisol ratio 1.41 +/- 0.16 vs. 1.12 +/- 0.17, P
      < 0.005). CONCLUSIONS: Obesity is associated with insulin resistance within
      adipose tissue and increased cortisol secretion rates; both are reversed with
      weight loss. Reduced 5alphaR activity after weight loss may decrease hypothalamo
      pituitary-adrenal axis activation and reduce glucocorticoid metabolite
      production.

PMID- 18340017
TI  - Mechanisms underlying caloric restriction and lifespan regulation: implications
      for vascular aging.
AB  - This review focuses on the emerging evidence that attenuation of the production
      of reactive oxygen species and inhibition of inflammatory pathways play a central
      role in the antiaging cardiovascular effects of caloric restriction. Particular
      emphasis is placed on the potential role of the plasma membrane redox system in
      caloric restriction-induced pathways responsible for sensing oxidative stress and
      increasing cellular oxidative stress resistance. We propose that caloric
      restriction increases bioavailability of NO, decreases vascular reactive oxygen
      species generation, activates the Nrf2/antioxidant response element pathway,
      inducing reactive oxygen species detoxification systems, exerts antiinflammatory
      effects, and, thereby, suppresses initiation/progression of vascular disease that
      accompany aging.

PMID- 18340019
TI  - Improving clinical instruction: comparison of literature.
AB  - CONTEXT: Clinical education in radiologic technology and athletic training is
      similar in that both programs use clinical sites and clinical instructors to
      instruct and evaluate student competency. OBJECTIVE: The purpose of this paper is
      to review and compare the literature from radiologic technology and athletic
      training clinical education. METHODS: The literature for this review was obtained
      using ProQuest and PubMed databases, from the years 1998 to 2006. Research is
      available for both radiologic technology and athletic training and provides a
      good comparison. RESULTS: Radiologic technology students experience various
      clinical stressors that can be remedied by properly trained clinical instructors
      and instructors who spend quality time with students. The opinions regarding the
      necessary behaviors of clinical instructors vary between program directors,
      clinical instructors and students. CONCLUSION: Cooperation and communication
      between programs and clinical instructors is important for students to achieve
      clinical success. A comparison of the literature demonstrates that radiologic
      technology and athletic training programs are similar; thus, ideas from athletic
      training can be applied to radiologic technology clinical education.

PMID- 18340020
TI  - An examination of factors related to radiation protection practices.
AB  - BACKGROUND: Radiation protection practices range from strict adherence to safety
      practices to complacency to unsafe procedures. Variations in compliance with
      safety practices can result in unnecessary radiation exposure to technologists
      and patients. OBJECTIVE: The objectives of this study were to advance the
      education and practice of the radiologic sciences by determining the degree of
      compliance with radiation safety practices as correlated to professional
      education, continuing education, years of employment in the radiologic sciences
      and work site. METHOD: A 32-item questionnaire was mailed to a national random
      sample of 2000 certified radiologic technologists. A return rate of 23.9% yielded
      454 questionnaires suitable for analysis. RESULTS: Mean scores for knowledge of
      and compliance with safety practices were 82% and 72%, respectively. Performance
      on individual items ranged from 95% compliance to 34% compliance. Two independent
      variables (ie, years of employment in the radiologic sciences and work site) were
      significantly related (P < .05) to adherence to safety practices. CONCLUSION:
      Results indicated the need for educational and organizational interventions to
      increase compliance with safety practices.

PMID- 18340021
TI  - How to review literature.

PMID- 18340022
TI  - Legal trends in imaging: an update.
AB  - In 2004, a similarly titled article,"Legal Trends in Imaging," was published in
      this Journal; it described medical malpractice cases involving imaging, the role
      of imaging in criminal trials and evolving legal concerns raised by newer imaging
      technologies. This article provides an update on the ever-expanding relationship
      between the law and imaging. Readers are cautioned that nothing contained in this
      article is intended as legal advice and should not be taken as such.

PMID- 18340023
TI  - Bladder cancer imaging.
AB  - Bladder cancer is a urinary system cancer, primarily afflicting older men.
      Smoking is the most significant risk factor. Symptoms include hematuria, urinary
      frequency or urinary urgency. Cystoscopy, radiologic techniques and biopsy
      results help health care providers diagnose, treat and monitor the disease. The
      prognosis of bladder cancer depends upon the invasiveness of the tumor and the
      extent of spread in the pelvic cavity. Treatment includes surgery, drug therapy,
      radiation therapy, chemotherapy or combinations thereof.

PMID- 18340025
TI  - Take it all off.

PMID- 18340026
TI  - Improving hospital-based programs II.

PMID- 18340027
TI  - RAs increase productivity.

PMID- 18340028
TI  - Low dose, high quality possible.

PMID- 18340029
TI  - Scoliosis and spine imaging.

PMID- 18340030
TI  - Patient page. Ultrasound during pregnancy.

PMID- 18340031
TI  - Parental styles, conscientiousness, and academic performance in high school: a
      three-wave longitudinal study.
AB  - This article assesses whether perceived parental style influenced the extent to
      which adolescents became increasingly conscientious and whether changes in
      conscientiousness influenced academic grades 1 year later. Parental styles,
      conscientiousness, verbal, and numerical ability at Time 1 were measured. One
      year later conscientiousness was again assessed, and 1 year after that end-of
      year exam results were obtained. More than 784 students (mean age=12.3 years,
      SD=0.49) participated in the 1st year. The data of 563 students were matched
      across the 3 years. Conscientiousness tended to decrease from Time 1 to Time 2.
      Structural equation modeling showed that adolescents with more authoritative
      parents experienced less of a decrease in conscientiousness at Time 2 than did
      students with less authoritative parents and the same baseline level of
      conscientiousness at Time 1. Additionally, the decrease in conscientiousness at
      Time 2 predicted worse grades at Time 3, even after controlling for baseline
      levels of academic achievement.

PMID- 18340032
TI  - Creating your own hostile environment: a laboratory examination of trait
      aggressiveness and the violence escalation cycle.
AB  - A dyadic interactive aggression paradigm tested hypotheses from the General
      Aggression Model about how trait aggressiveness can create behaviorally hostile
      social environments. Pairs of college student participants competed in a modified
      reaction time task in which they repeatedly delivered and received each other's
      punishments. The trait aggressiveness of both participants influenced the
      punishment intensities (aggression level) set by each member of the dyad on later
      trials. Furthermore, there was a pattern of escalation from early to later
      trials. These trait aggressiveness effects (both self and partner) on later
      aggressive behavior were largely mediated by partner aggression levels during
      early trials. Results also suggested two aggressive motives--hostile and
      instrumental--resulted from high partner aggression during early trials and these
      motives partially mediated the effects of trait aggressiveness and of early trial
      aggression on later aggressive behavior.

PMID- 18340033
TI  - What happens when groups say sorry: the effect of intergroup apologies on their
      recipients.
AB  - Despite the increased incidence of intergroup apology in public life, very little
      empirical attention has been paid to the questions of whether intergroup
      apologies work and if so, why. In a series of experiments, Australians read
      scenarios in which Australian interests had been harmed by an outgroup.
      Participants were then told that the outgroup had either apologized or had not
      apologized for the offense. Although the presence of an apology helped promote
      perceptions that the outgroup was remorseful, and although participants were more
      satisfied with an apology than with no apology, the presence of the apology
      failed to promote forgiveness for the offending group. This was the case
      regardless of whether the effectiveness of apology was measured cross-sectionally
      (Experiment 1) or longitudinally (Experiment 2). It was also the case when the
      apology was accompanied by victims advocating forgiveness (Experiment 3) and was
      independent of the emotionality of the apology (Experiment 4). In contrast,
      individuals who apologized for intergroup atrocities were personally forgiven
      more than those who did not apologize (Experiment 4). Theoretical and applied
      implications are discussed.

PMID- 18340034
TI  - Gender differences in interpersonal complementarity within roommate dyads.
AB  - Complementarity theory proposes specific hypotheses regarding interpersonal
      styles that will result in successful relationships. The present study sought to
      extend previous research on gender differences in complementarity through the
      examination of same-sex peer dyads and the use of informant reports of
      interpersonal style. One hundred twenty participants (30 male and 30 female
      roommate dyads) completed interpersonal circumplex ratings of their roommates and
      a relationship cohesion measure. Examinations of complementarity indicate that
      women reported significantly more complementarity than men within their roommate
      dyads. However, for men and women, the closer the dyad was to perfect
      complementarity in terms of dominance, the more cohesive the relationship.
      Results are discussed in relation to gender differences in social development.

PMID- 18340035
TI  - Justice for whom, exactly? Beliefs in justice for the self and various others.
AB  - The present studies examine why people think the world is more just to themselves
      than to others generally. Beliefs in justice for the self were uniquely
      associated with psychological adjustment, consistent with the theoretical motive
      to believe in justice for the self (Studies 1 and 2). However, this "justice
      motive" did not appear to affect the relative strength of justice beliefs.
      Instead, self-other differences in justice beliefs appeared to reflect objective
      assessments of the justice received by various demographics. Undergraduates
      believed the world to be more just to themselves than to others but not their
      undergraduate peers specifically (Study 1). Participants of both genders believed
      the world to be more just to men, and to themselves, than to women (Study 2).
      Women did not exempt themselves individually from injustice but believed, similar
      to men, that undergraduate women receive as much justice as men (Study 3).

PMID- 18340036
TI  - Reciprocal effects between academic self-concept, self-esteem, achievement, and
      attainment over seven adolescent years: unidimensional and multidimensional
      perspectives of self-concept.
AB  - In their influential review, Baumeister, Campbell, Krueger, and Vohs (2003)
      concluded that self-esteem--the global component of self-concept--has no effect
      on subsequent academic performance. In contrast, Marsh and Craven's (2006) review
      of reciprocal effects models from an explicitly multidimensional perspective
      demonstrated that academic self-concept and achievement are both a cause and an
      effect of each other. Ironically, both reviews cited classic Youth in Transition
      studies in support of their respective claims. In definitive tests of these
      counter claims, the authors reanalyze these data-including self-esteem
      (emphasized by Baumeister et al.), academic self-concept (emphasized by Marsh &
      Craven), and postsecondary educational attainment-using stronger statistical
      methods based on five waves of data (grade 10 through 5 years after graduation;
      N=2,213). Integrating apparently discrepant findings under a common theoretical
      framework based on a multidimensional perspective, academic self-concept had
      consistent reciprocal effects with both achievement and educational attainment,
      whereas self-esteem had almost none.

PMID- 18340037
TI  - Attitudinal ambivalence and message-based persuasion: motivated processing of
      proattitudinal information and avoidance of counterattitudinal information.
AB  - Attitudinal ambivalence has been found to increase processing of attitude
      relevant information. In this research, the authors suggest that ambivalence can
      also create the opposite effect: avoidance of thinking about persuasive messages.
      If processing is intended to reduce experienced ambivalence, then ambivalent
      people should increase processing of information perceived as proattitudinal
      (agreeable) and able to decrease ambivalence. However, ambivalence should also
      lead people to avoid processing of counterattitudinal (disagreeable) information
      that threatens to increase ambivalence. Three studies provide evidence consistent
      with this proposal. When participants were relatively ambivalent, they processed
      messages to a greater extent when the messages were proattitudinal rather than
      counterattitudinal. However, when participants were relatively unambivalent, they
      processed messages more when the messages were counterattitudinal rather than
      proattitudinal. In addition, ambivalent participants perceived proattitudinal
      messages as more likely than counterattitudinal messages to reduce ambivalence,
      and these perceptions accounted for message position effects on amount of
      processing.

PMID- 18340039
TI  - ALLPATHS: de novo assembly of whole-genome shotgun microreads.
AB  - New DNA sequencing technologies deliver data at dramatically lower costs but
      demand new analytical methods to take full advantage of the very short reads that
      they produce. We provide an initial, theoretical solution to the challenge of de
      novo assembly from whole-genome shotgun "microreads." For 11 genomes of sizes up
      to 39 Mb, we generated high-quality assemblies from 80x coverage by paired 30
      base simulated reads modeled after real Illumina-Solexa reads. The bacterial
      genomes of Campylobacter jejuni and Escherichia coli assemble optimally, yielding
      single perfect contigs, and larger genomes yield assemblies that are highly
      connected and accurate. Assemblies are presented in a graph form that retains
      intrinsic ambiguities such as those arising from polymorphism, thereby providing
      information that has been absent from previous genome assemblies. For both C.
      jejuni and E. coli, this assembly graph is a single edge encompassing the entire
      genome. Larger genomes produce more complicated graphs, but the vast majority of
      the bases in their assemblies are present in long edges that are nearly always
      perfect. We describe a general method for genome assembly that can be applied to
      all types of DNA sequence data, not only short read data, but also conventional
      sequence reads.

PMID- 18340040
TI  - Multiple waves of recent DNA transposon activity in the bat, Myotis lucifugus.
AB  - DNA transposons, or class 2 transposable elements, have successfully propagated
      in a wide variety of genomes. However, it is widely believed that DNA transposon
      activity has ceased in mammalian genomes for at least the last 40 million years.
      We recently reported evidence for the relatively recent activity of hAT and
      Helitron elements, two distinct groups of DNA transposons, in the lineage of the
      vespertilionid bat Myotis lucifugus. Here, we describe seven additional families
      that have also been recently active in the bat lineage. Early vespertilionid
      genome evolution was dominated by the activity of Helitrons, mariner-like and Tc2
      like elements. This was followed by the colonization of Tc1-like elements, and by
      a more recent explosion of hAT-like elements. Finally, and most recently,
      piggyBac-like elements have amplified within the Myotis genome and our results
      indicate that one of these families is probably still expanding in natural
      populations. Together, these data suggest that there has been tremendous recent
      activity of various DNA transposons in the bat lineage that far exceeds those
      previously reported for any mammalian lineage. The diverse and recent populations
      of DNA transposons in genus Myotis will provide an unprecedented opportunity to
      study the impact of this class of elements on mammalian genome evolution and to
      better understand what makes some species more susceptible to invasion by genomic
      parasites than others.

PMID- 18340041
TI  - Genome-wide analysis of Fis binding in Escherichia coli indicates a causative
      role for A-/AT-tracts.
AB  - We determined the genome-wide distribution of the nucleoid-associated protein Fis
      in Escherichia coli using chromatin immunoprecipitation coupled with high
      resolution whole genome-tiling microarrays. We identified 894 Fis-associated
      regions across the E. coli genome. A significant number of these binding sites
      were found within open reading frames (33%) and between divergently transcribed
      transcripts (5%). Analysis indicates that A-tracts and AT-tracts are an important
      signal for preferred Fis-binding sites, and that A(6)-tracts in particular
      constitute a high-affinity signal that dictates Fis phasing in stretches of DNA
      containing multiple and variably spaced A-tracts and AT-tracts. Furthermore, we
      find evidence for an average of two Fis-binding regions per supercoiling domain
      in the chromosome of exponentially growing cells. Transcriptome analysis shows
      that approximately 21% of genes are affected by the deletion of fis; however, the
      changes in magnitude are small. To address the differential Fis bindings under
      growth environment perturbation, ChIP-chip analysis was performed using cells
      grown under aerobic and anaerobic growth conditions. Interestingly, the Fis
      binding regions are almost identical in aerobic and anaerobic growth conditions
      indicating that the E. coli genome topology mediated by Fis is superficially
      identical in the two conditions. These novel results provide new insight into how
      Fis modulates DNA topology at a genome scale and thus advance our understanding
      of the architectural bases of the E. coli nucleoid.

PMID- 18340042
TI  - Genomic evolution of the placenta using co-option and duplication and divergence.
AB  - The invention of the placenta facilitated the evolution of mammals. How the
      placenta evolved from the simple structure observed in birds and reptiles into
      the complex organ that sustains human life is one of the great mysteries of
      evolution. By using a timecourse microarray analysis including the entire
      lifetime of the placenta, we uncover molecular and genomic changes that underlie
      placentation and find that two distinct evolutionary mechanisms were utilized
      during placental evolution in mice and human. Ancient genes involved in growth
      and metabolism were co-opted for use during early embryogenesis, likely enabling
      the accelerated development of extraembryonic tissues. Recently duplicated genes
      are utilized at later stages of placentation to meet the metabolic needs of a
      diverse range of pregnancy physiologies. Together, these mechanisms served to
      develop the specialized placenta, a novel structure that led to expansion of the
      eutherian mammal, including humankind.

PMID- 18340043
TI  - Quantitative evidence for conserved longevity pathways between divergent
      eukaryotic species.
AB  - Studies in invertebrate model organisms have been a driving force in aging
      research, leading to the identification of many genes that influence life span.
      Few of these genes have been examined in the context of mammalian aging, however,
      and it remains an open question as to whether and to what extent the pathways
      that modulate longevity are conserved across different eukaryotic species. Using
      a comparative functional genomics approach, we have performed the first
      quantitative analysis of the degree to which longevity genes are conserved
      between two highly divergent eukaryotic species, the yeast Saccharomyces
      cerevisiae and the nematode Caenorhabditis elegans. Here, we report the
      replicative life span phenotypes for single-gene deletions of the yeast orthologs
      of worm aging genes. We find that 15% of these yeast deletions are long-lived. In
      contrast, only 3.4% of a random set of deletion mutants are long-lived-a
      statistically significant difference. These data suggest that genes that modulate
      aging have been conserved not only in sequence, but also in function, over a
      billion years of evolution. Among the longevity determining ortholog pairs, we
      note a substantial enrichment for genes involved in an evolutionarily conserved
      pathway linking nutrient sensing and protein translation. In addition, we have
      identified several conserved aging genes that may represent novel longevity
      pathways. Together, these findings indicate that the genetic component of life
      span determination is significantly conserved between divergent eukaryotic
      species, and suggest pathways that are likely to play a similar role in mammalian
      aging.

PMID- 18340044
TI  - Evaluating laboratory diagnostic tests.

PMID- 18340045
TI  - Illness in people with intellectual disabilities.

PMID- 18340046
TI  - Government's response to the Tooke inquiry into Modernising Medical Careers.

PMID- 18340047
TI  - Diabetes education: Pilot educational interventions.

PMID- 18340048
TI  - Diabetes education: Selection bias in cluster trial.

PMID- 18340049
TI  - Tackling alcohol misuse: Typical British malaise.

PMID- 18340050
TI  - Tackling alcohol misuse: Needs in adolescents.

PMID- 18340051
TI  - Private companies and GPs: An inconvenient truth.

PMID- 18340052
TI  - Private companies and GPs: A crucial juncture.

PMID- 18340053
TI  - Joining the DOTS: National "twin study".

PMID- 18340055
TI  - UK government will tighten law on trial results after weaknesses found in safety
      legislation.

PMID- 18340056
TI  - Company managed to block development of generic drug.

PMID- 18340059
TI  - China wants to make health care more affordable to poor.

PMID- 18340061
TI  - Rich states "snatch" trained doctors from countries.

PMID- 18340064
TI  - 94% of patients suing Merck over rofecoxib agree to company's offer.

PMID- 18340065
TI  - Poor communication, poor training, and chaotic drug rounds contribute to drug
      errors.

PMID- 18340066
TI  - People with learning difficulties face abuse in health settings.

PMID- 18340068
TI  - Doctors hope consensus on brain death in China will boost transplants.

PMID- 18340070
TI  - Cabin fever.

PMID- 18340071
TI  - The gene detective.

PMID- 18340072
TI  - Biologically speaking, parliament decides there is no alternative.

PMID- 18340073
TI  - The return of the spoof.

PMID- 18340074
TI  - Genetic tests for common diseases: new insights, old concerns.

PMID- 18340075
TI  - Prescribing for older people.

PMID- 18340076
TI  - Diagnosis and treatment of prostate cancer: summary of NICE guidance.

PMID- 18340077
TI  - Commentary: controversies in NICE guidance on prostate cancer.

PMID- 18340078
TI  - Don't add aspirin for associated stable vascular disease in a patient with atrial
      fibrillation receiving anticoagulation.

PMID- 18340083
TI  - Glycosylation of Asn-76 in mouse GPIHBP1 is critical for its appearance on the
      cell surface and the binding of chylomicrons and lipoprotein lipase.
AB  - GPIHBP1 is a glycosylphosphatidylinositol-anchored protein in the lymphocyte
      antigen 6 (Ly-6) family that recently was identified as a platform for the
      lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 binds both LPL
      and chylomicrons and is expressed on the luminal face of microvascular
      endothelial cells. Here, we show that mouse GPIHBP1 is N-glycosylated at Asn-76
      within the Ly-6 domain. Human GPIHBP1 is also glycosylated. The N-linked glycan
      could be released from mouse GPIHBP1 with N-glycosidase F, endoglycosidase H, or
      endoglycosidase F1. The glycan was marginally sensitive to endoglycosidase F2
      digestion but resistant to endoglycosidase F3 digestion, suggesting that the
      glycan on GPIHBP1 is of the oligomannose type. Mutating the N-glycosylation site
      in mouse GPIHBP1 results in an accumulation of GPIHBP1 in the endoplasmic
      reticulum and a markedly reduced amount of the protein on the cell surface.
      Consistent with this finding, cells expressing a nonglycosylated GPIHBP1 lack the
      ability to bind LPL or chylomicrons. Eliminating the N-glycosylation site in a
      truncated soluble version of GPIHBP1 causes a modest reduction in the secretion
      of the protein. These studies demonstrate that N-glycosylation of GPIHBP1 is
      important for the trafficking of GPIHBP1 to the cell surface.

PMID- 18340084
TI  - Integrating a school-based health intervention in times of high-stakes testing:
      lessons learned from full court press.
AB  - Because of the growing focus on the production of favorable academic standardized
      test scores, schools have become increasingly resistant to sponsoring nonacademic
      programming, such as tobacco cessation services for students. Nevertheless, the
      need for such programs has not diminished. The purpose of this article is to
      provide descriptive information about the logistics of establishing and
      delivering a health intervention in schools that are resistant to nonacademic
      programming. The data were collected as part of a qualitative retrospective
      process evaluation of Full Court Press, a 5-year youth tobacco demonstration
      project funded by the Robert Woods Johnson Foundation and implemented in Tucson,
      Arizona. Lessons learned about recruiting schools, integrating programs, and
      managing facilitators are presented.

PMID- 18340085
TI  - Informing best practice with community practice: the community change chronicle
      method for program documentation and evaluation.
AB  - Health promotion professionals are increasingly encouraged to implement evidence
      based programs in health departments, communities, and schools. Yet translating
      evidence-based research into practice is challenging, especially for complex
      initiatives that emphasize environmental strategies to create community change.
      The purpose of this article is to provide health promotion practitioners with a
      method to evaluate the community change process and document successful
      applications of environmental strategies. The community change chronicle method
      uses a five-step process: first, develop a logic model; second, select outcomes
      of interest; third, review programmatic data for these outcomes; fourth, collect
      and analyze relevant materials; and, fifth, disseminate stories. From 2001 to
      2003, the authors validated the use of a youth empowerment model and developed
      eight community change chronicles that documented the creation of tobacco-free
      schools policies (n = 2), voluntary policies to reduce secondhand smoke in youth
      hangouts (n = 3), and policy and program changes in diverse communities (n = 3).

PMID- 18340086
TI  - Using pretesting to ensure your messages and materials are on strategy.
AB  - Pretesting is an important demonstration of understanding consumers' wants and
      preferences. This evolving, data-driven process provides opportunity for ensuring
      time, effort, and valuable resources are not wasted. The purpose of this article
      is to clarify the process of pretesting, why one should pretest, common mistakes,
      and pretesting on a shoestring budget.

PMID- 18340087
TI  - Applying health education theory to patient safety programs: three case studies.
AB  - Program planning for patient safety is challenging because intervention-oriented
      surveillance data are not yet widely available to those working in this nascent
      field. Even so, health educators are uniquely positioned to contribute to patient
      safety intervention efforts because their theoretical training provides them with
      a guide for designing and implementing prevention programs. This article
      demonstrates the utility of applying health education concepts from three
      prominent patient safety campaigns, including the concepts of risk perception,
      community participation, and social marketing. The application of these
      theoretical concepts to patient safety programs suggests that health educators
      possess a knowledge base and skill set highly relevant to patient safety and that
      their perspective should be increasingly brought to bear on the design and
      evaluation of interventions that aim to protect patients from preventable medical
      error.

PMID- 18340088
TI  - Defining elements of success: a critical pathway of coalition development.
AB  - In recent decades, coalitions have been established to address many public health
      problems, including injury prevention. A partnership among the Kentucky Injury
      Prevention and Research Center and four injury prevention coalitions has
      documented the developmental stages of successful coalitions. This developmental
      process was constructed through the analysis of participating coalition
      documents, such as each coalition's mission statement, bylaws or rules of
      operation, the use of committees within the organization, frequency of meetings,
      and additional historical documents. Themes from this analysis guided researchers
      in designing a critical pathway model that describes milestones in coalition
      formation. Critical components in coalition formation include a clear definition
      of the coalition structure, coalition enhancement, funding, community support,
      leadership, education and outreach to the community, membership, partnerships,
      data and evaluation, and publicity. These findings are applicable to public
      health professionals who work with community-based coalitions and citizens who
      participate in local coalitions.

PMID- 18340089
TI  - Abnormal mammogram follow-up: do community lay health advocates make a
      difference?
AB  - This pilot study evaluates a community lay health advocate (CLHA) intervention in
      promoting follow-up for abnormal mammograms among African American women. A
      controlled trial was implemented at an urban hospital in Atlanta, with 48 women
      in a CLHA intervention group and 35 in a usual care group. Participants were 25
      or older and had an abnormal mammogram between March 25, 2002, and May 2, 2003.
      Intervention group women received CLHA support including encouragement of timely
      abnormal mammogram follow-up, reminders of follow-up appointments, identification
      and removal of barriers to follow-up, and accompaniment to follow-up
      appointments. Women in the intervention group were significantly more likely to
      keep their first abnormal mammogram follow-up appointment, all of their scheduled
      follow-up appointments, and their biopsy or fine needle aspiration appointment.
      CLHAs are effective in promoting abnormal mammogram followup among African
      American women and may be an important resource in reducing racial disparities in
      breast cancer mortality.

PMID- 18340090
TI  - Culturally responsive health promotion in puerto rican communities: a
      structuralist approach.
AB  - This literature review discusses the value of the structuralist approach as an
      integrated theoretical and methodological framework for participatory cultural
      assessments designed to capture the cultural dynamics of those affected by health
      disparities. Drawing from principles of the Levi-Straussian strand of structural
      anthropology found in contemporary cultural studies, and using the Puerto Rican
      cultural experience as an example, the authors present the distinction between
      deep and surface structures of cultural knowledge and meaning and highlight
      information-processing and behavioral systems influenced by the complexity of
      cognitive and social representations of cultural structures. To understand and
      address the deeply rooted web of ideology, norms, and practices that influence
      health decision making and behavioral responses, the authors show the need for
      ethnographic narrative inquiry beyond surface manifestations of culture. Finally,
      the authors discuss the implications of the structuralist approach for culturally
      responsive health education and other health promotion interventions.

PMID- 18340091
TI  - Endovascular thrombectomy and thrombolysis for severe cerebral sinus thrombosis:
      a prospective study.
AB  - BACKGROUND AND PURPOSE: Most patients with cerebral sinus thrombosis (CST)
      recover after treatment with heparin, but a subgroup has a poor prognosis. Those
      patients may benefit from endovascular thrombolysis. METHODS: Prospective case
      series. Patients with sinus thrombosis were selected for thrombolysis if they had
      an altered mental status, coma, straight sinus thrombosis, or large space
      occupying lesions. Urokinase was infused into the sinuses (bolus 120 to 600 x
      10(3) U; then 100 x 10(3) U/h) via a jugular catheter, in 15 cases combined with
      mechanical thrombus disruption or removal. RESULTS: We treated 20 patients (16
      women), mean age 32 years. Twelve patients were comatose and 14 had hemorrhagic
      infarcts before thrombolysis. Twelve patients recovered (Rankin score 0 to 2), 2
      survived with handicaps, and 6 died. Factors associated with a fatal outcome were
      leukemia (3/6 versus 0/14, P=0.02) and large hemorrhagic infarcts (4/6 versus
      2/14, P=0.04). Seizures were less frequent in the fatal cases (P=0.05). Patients
      who died had a larger mean lesion surface than survivors (30.5 versus 13.6 cm(2);
      P=0.03), larger midline shift (5.2 versus 1.7 mm; P=0.02), and a more rapid
      course (2.7 versus 8.2 days; P=0.01). Five patients who died had large
      hemispheric infarcts and edema before thrombolysis, causing herniation. Five
      patients had increased cerebral hemorrhage (3 minor, 2 major) after thrombolysis.
      CONCLUSIONS: Thrombolysis can be effective for severe sinus thrombosis, but
      patients may deteriorate because of increased cerebral hemorrhage. Patients with
      large infarcts and impending herniation did not benefit.

PMID- 18340092
TI  - Functional MRI correlates of lower limb function in stroke victims with gait
      impairment.
AB  - BACKGROUND AND PURPOSE: Although knowledge concerning cortical reorganization
      related to upper limb function after ischemic stroke is growing, similar data for
      lower limb movements are limited. Previous studies with hand movement suggested
      increasing recruitment of motor areas in the unlesioned hemisphere with
      increasing disability. We used ankle movement as a lower limb analog to test for
      similarities and differences in recovery patterns. METHODS: Eighteen subjects
      were selected with chronic residual gait impairment due to a single subcortical
      ischemic stroke. Functional MRI scans were obtained at 3.0 T during active and
      passive ankle dorsiflexion in the patients (8 females, 10 males; mean age, 59.9+/
      13.5 years; range, 32 to 74 years) and 18 age-matched healthy control subjects.
      RESULTS: We observed substantial neocortical activity associated with foot
      movement both in the patients with stroke and in the healthy control subjects.
      Our primary finding was increased cortical activation with increasing functional
      impairment. The extent of activation (particularly in the primary sensorimotor
      cortex and the supplementary motor area of the unlesioned hemisphere) increased
      with disability. The changes were most prominent with the active movement task.
      CONCLUSIONS: Using ankle movement, we observed increased activation in the
      unlesioned hemisphere associated with worse function of the paretic leg,
      consistent with studies on movement of paretic upper limbs. We interpret this
      finding as potentially adaptive recruitment of undamaged ipsilateral motor
      control pathways from the supplementary motor area and (possibly maladaptive)
      disinhibition of the ipsilateral sensorimotor cortex.

PMID- 18340093
TI  - Severity of leukoaraiosis and susceptibility to infarct growth in acute stroke.
AB  - BACKGROUND AND PURPOSE: Leukoaraiosis (LA) is associated with structural and
      functional vascular changes that may compromise tissue perfusion at the
      microvascular level. We hypothesized that the volume of LA correlated with the
      proportion of initially ischemic but eventually infarcted tissue in acute human
      stroke. METHODS: We studied 61 consecutive patients with diffusion-weighted
      imaging-mean transit time mismatch. All patients were scanned twice within 12
      hours of symptom onset and between days 4 and 30. We explored the relationship
      between the volume of white matter regions with LA on acute images and the
      proportion of diffusion-weighted imaging-mean transit time mismatch tissue that
      progressed to infarction (percentage mismatch lost). RESULTS: Bivariate analyses
      showed a statistically significant correlation between percentage mismatch lost
      and LA volume (r=0.33, P<0.01). A linear regression model with percentage
      mismatch lost as response and LA volume, acute diffusion-weighted imaging and
      mean transit time volumes, age, admission blood glucose level, admission mean
      arterial blood pressure, etiologic stroke subtype, time to acute MRI, and time
      between acute and follow-up imaging as covariates revealed that LA volume was an
      independent predictor of infarct growth (P=0.04). The adjusted percentage
      mismatch lost in the highest quartile of LA volume was 1.9-fold (95% CI: 1.2 to
      3.1) greater than the percentage mismatch lost in the lowest quartile.
      CONCLUSIONS: LA volume at the time of acute ischemic stroke is a predictor
      infarct growth. Because LA is associated with factors that modulate tissue
      perfusion as well as tissue capacity for handling of ischemia, LA volume appears
      to be a composite predictive marker for the fate of acutely ischemic tissue.

PMID- 18340094
TI  - Racial and ethnic differences in postacute rehabilitation outcomes after stroke
      in the United States.
AB  - BACKGROUND AND PURPOSE: Incidence, prevalence, and mortality for stroke vary by
      race and ethnicity with higher rates for blacks compared with non-Hispanic
      whites. Little information is available regarding differences in postacute care
      outcomes for racial and ethnic groups after a stroke. METHODS: A retrospective
      analysis was conducted of 161,692 patients from the Uniform Data System for
      Medical Rehabilitation who received inpatient medical rehabilitation after a
      first stroke in 2002 and 2003. Multivariable models examined the effects of race
      and ethnicity on length of stay, functional status, rehabilitation efficiency,
      and discharge setting. RESULTS: The mean age was 70.97 years (SD=12.87), 53% were
      female, and 76% were non-Hispanic white. Mean length of stay was similar for all
      groups ranging from 17.39 days (SD=10.86) to 17.93 (SD=10.59). Non-Hispanic white
      patients had higher admission and discharge functional status ratings compared
      with patients in the minority groups (P<0.01). Differences in functional status
      across racial/ethnic groups were related to age (F=20.49, P<0.001); the older the
      comparison group, the greater the difference in functional status. Non-Hispanic
      whites were discharged home less often than blacks (OR=0.64, 95% CI=0.62 to
      0.66), Hispanics (OR=0.58, 95% CI=0.55 to 0.62), or other minority groups
      (OR=0.67, 95% CI=0.57 to 0.67). CONCLUSIONS: The findings suggest racial and
      ethnic disparities exist in postacute care outcomes for persons with stroke.

PMID- 18340095
TI  - Mild induced hypertension improves blood flow and oxygen metabolism in transient
      focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: In focal ischemic cortex, cerebral blood flow
      autoregulation is impaired, and perfusion passively follows blood pressure
      variations. Although it is generally agreed that profound hypotension is harmful
      in acute stroke, the hemodynamic and metabolic impact of increased blood pressure
      on the ischemic core and penumbra are less well understood. We, therefore, tested
      whether pharmacologically induced hypertension improves cerebral blood flow and
      metabolism and tissue outcome in acute stroke using optical imaging with high
      spatiotemporal resolution. METHODS: Cerebral blood flow, oxyhemoglobin, and
      cerebral metabolic rate of oxygen were measured noninvasively using simultaneous
      multispectral reflectance imaging and laser speckle flowmetry during distal
      middle cerebral artery occlusion in mice. Hypertension was induced by
      phenylephrine infusion starting 10 or 60 minutes after ischemia to raise blood
      pressure by 30% for the duration of ischemia; control groups received saline
      infusion. RESULTS: Mild induced hypertension rapidly increased cerebral blood
      flow, oxyhemoglobin, and cerebral metabolic rate of oxygen in both the core and
      penumbra and prevented the expansion of cerebral blood flow deficit during 1 hour
      distal middle cerebral artery occlusion. Induced hypertension also diminished the
      deleterious effects of periinfarct depolarizations on cerebral blood flow,
      oxyhemoglobin, and cerebral metabolic rate of oxygen without altering their
      frequency. Consistent with this, mild induced hypertension reduced infarct volume
      by 48% without exacerbating tissue swelling when measured 2 days after 1 hour
      transient distal middle cerebral artery occlusion. CONCLUSIONS: Our data suggest
      that mild induced hypertension increases collateral cerebral blood flow and
      oxygenation and improves cerebral metabolic rate of oxygen in the core and
      penumbra, supporting its use as bridging therapy in acute ischemic stroke until
      arterial recanalization is achieved.

PMID- 18340096
TI  - Observation of the lenticulostriate arteries in the human brain in vivo using
      7.0T MR angiography.
AB  - BACKGROUND AND PURPOSE: We sought to examine the feasibility of observing the
      lenticulostriate arteries (LSAs) noninvasively by ultrahigh-field MRI with 7.0T.
      METHODS: We used 3-dimensional time-of-flight MR angiography with a
      radiofrequency coil optimized for 7.0T MRI. We examined the LSAs of 6 healthy
      subjects and compared 7.0T MR angiography images with 1.5T ones to examine the
      potentials of ultrahigh-field MRI for angiography. RESULTS: The results show
      clear details of LSAs and their distribution in the normal healthy subjects with
      large variations in the shapes, the number of branches and the sites of origin.
      We also observed substantial differences between the left and right sides within
      each subject. Although we studied only 6 subjects, we found no age- or gender
      related differences in the LSAs. CONCLUSIONS: The visualization of
      microvasculature of the brain, such as LSAs, using 7.0T MR angiography, is
      possible in in vivo human studies noninvasively. We, therefore, believe that it
      could play a major role in the study of small vascular abnormalities, such as the
      early stages of cerebral strokes.

PMID- 18340097
TI  - Middle cerebral artery occlusion in the rabbit using selective angiography:
      application for assessment of thrombolysis.
AB  - BACKGROUND AND PURPOSE: An animal model of selective middle cerebral artery (MCA)
      occlusion is needed for evaluation of intra-arterial (IA) delivery of
      thrombolytic agents. We describe a technique for MCA thrombo-occlusion in the
      rabbit with real-time angiographic documentation of occlusion and thrombolytic
      recanalization. METHODS: After femoral artery cutdown, a microcatheter was
      advanced from the internal carotid artery to the MCA. MCA occlusion was achieved
      by IA thrombin and reperfusion by IA plasmin. RESULTS: The terminal internal
      carotid artery was successfully catheterized in 12 of 13 animals. Stable (2-hour)
      MCA occlusion was induced and verified angiographically in all 12 animals; 2
      animals also had distal internal carotid artery thrombus. Recanalization was
      achieved rapidly after IA plasmin in 3 of 3 animals. CONCLUSIONS: We describe a
      new animal model of selective MCA occlusion documented by real-time angiography
      and used to demonstrate recanalization with IA plasmin.

PMID- 18340098
TI  - Leukoaraiosis: from an ancient term to an actual marker of poor prognosis.

PMID- 18340099
TI  - Ultrasound-enhanced thrombolysis: from bedside to bench.

PMID- 18340100
TI  - Sonothrombolysis with transcranial color-coded sonography and recombinant tissue
      type plasminogen activator in acute middle cerebral artery main stem occlusion:
      results from a randomized study.
AB  - BACKGROUND AND PURPOSE: Sonothrombolysis is a new treatment approach in acute
      ischemic stroke. The results of a monocenter, randomized clinical study are
      presented. METHODS: Subjects with acute middle cerebral artery main stem
      occlusion were randomized into a target group receiving 1-hour transcranial
      continuous insonation using a 1.8-MHz Doppler ultrasound (US) probe or a control
      group. All underwent standard thrombolysis with intravenous recombinant tissue
      type plasminogen activator. RESULTS: Thirty-seven subjects were included; 19
      subjects were treated in the target (US) group and 18 in the control (no-US)
      group, all with no residual flow in the middle cerebral artery main stem
      occlusion (Thrombolysis in Brain Ischemia recanalization grade 0). Compared with
      the no-US group, the US group showed greater improvement in National Institutes
      of Health Stroke Scale values at days 1 and 4 and a higher median Thrombolysis in
      Brain Ischemia grade 1 hour after recombinant tissue-type plasminogen activator
      initiation. Recanalization (complete or partial) after 1 hour occurred in 57.9%
      of the US group and 22.2% of the no-US group (P=0.045). After 90 days, 4 subjects
      from the US group had a modified Rankin Score <or=1 (none from the no-US group)
      and 8 had a Barthel Index >or=95 (none from the no US group; P=0.106 and P=0.003,
      respectively). Three subjects from the US group (15.8%) developed a symptomatic
      intracranial hemorrhage as did one (5.6%) in the no-US group (P=0.60).
      CONCLUSIONS: This small randomized study indicates a beneficial impact of
      transcranial ultrasound on recanalization and short-term outcome in subjects with
      middle cerebral artery main stem occlusion and recombinant tissue-type
      plasminogen activator treatment.

PMID- 18340101
TI  - Whole genome analyses suggest ischemic stroke and heart disease share an
      association with polymorphisms on chromosome 9p21.
AB  - BACKGROUND AND PURPOSE: Recently independent studies reported an association
      between coronary heart disease and single-nucleotide polymorphisms (SNPs) located
      at chromosome 9p21, near CDKN2A and CDKN2B genes. Given that stroke is a common
      complication after myocardial infarction, we investigated if the same SNPs were
      associated with ischemic stroke in our population. METHODS: We recently initiated
      a whole genome analysis of ischemic stroke and published the first stage of a
      case control study using >400,000 SNPs from Illumina Infinium Human-1 and
      HumanHap300 assays. We focused on SNPs recently associated with heart disease by
      Helgadottir and colleagues and SNPs from the same haplotype block. RESULTS: In
      analyses both unadjusted and adjusted for stroke risk factors, significant
      associations with ischemic stroke were observed for SNPs from the same haplotype
      block previously associated with myocardial infarction. Significant association
      was also seen between disease and haplotypes involving these SNPs, both with and
      without adjustment for stroke risk factors (odd ratios: 1.01 to 2.65).
      CONCLUSIONS: These data are important for 3 reasons: first, they suggest a
      genetic association for stroke; second, they suggest that this association shares
      pathogenic mechanisms with heart disease and diabetes; and third, they
      illustrate, that public release of data can facilitate rapid risk locus
      discovery.

PMID- 18340102
TI  - Morphological but not functional changes of the carotid artery are associated
      with the extent of coronary artery disease in patients with preserved left
      ventricular function.
AB  - BACKGROUND AND PURPOSE: The atherosclerotic process is associated with both
      morphological and functional changes in the carotid artery. We evaluated the
      relationship between these parameters of the carotid artery and the extent of
      coronary artery disease (CAD) in patients with preserved left ventricular
      function. METHODS: The study population consisted of 104 stable patients with CAD
      who had preserved left ventricular function (left ventricular ejection fraction
      >or=45%). All patients underwent carotid ultrasound for evaluation of carotid
      artery plaque score defined by the sum of plaque thickness, maximum percent area
      stenosis, and carotid arterial stiffness index beta calculated by a combination
      of changes in carotid arterial diameter and blood pressure. RESULTS: Plaque score
      and percent area stenosis correlated with the extent of CAD defined as the number
      of diseased coronary vessels (P<0.001 and 0.002, respectively), but arterial
      stiffness beta did not (P=0.39). Using logistic regression analyses adjusting for
      confounding coronary risk factors and arterial stiffness beta, plaque score and
      percent area stenosis were independently correlated with multivessel CAD (P=0.001
      and 0.004, respectively). CONCLUSIONS: Carotid artery plaque burden, but not
      arterial stiffness, is associated with the extent of CAD, suggesting
      morphological rather than functional changes in the carotid artery may be a more
      accurate predictor of the extent of CAD and multivessel CAD independent of left
      ventricular function.

PMID- 18340103
TI  - Effect of encoding condition on source memory for odors in healthy young and
      older adults.
AB  - BACKGROUND: Source memory has been shown to be more affected by aging than item
      memory. Aging also has been shown to result in impairments in odor memory.
      OBJECTIVE: The aim of the study is to examine the effects of explicit encoding
      instructions on source memory for olfactory stimuli in healthy older and young
      adults. METHODS: Source and item memory for odors were assessed in two
      conditions. In the uninformed condition, young (18-30) and older adults (65+)
      were presented with 16 odors by two sources (male and female) without instruction
      at encoding and no warning of a subsequent memory task. In the informed
      condition, young and older adults were instructed to encode the stimuli and their
      respective sources. To assess item memory, the participant was presented with an
      odor from the task and a new odor and was asked to indicate which odor had been
      presented previously. On source memory trials, the participant was presented with
      an odor from the task and was asked to indicate whether the male or female
      presented the odor. RESULTS: A 2 x 2 x 2 analysis of variance revealed that older
      adults were significantly impaired relative to young adults on the source memory
      trials in both the uninformed and informed conditions, F(1, 52) = 18.15, p <
      0.001. However, older adults matched the performance of young adults on item
      memory trials, regardless of encoding condition. CONCLUSIONS: Even with conscious
      effort to encode the sources associated with the odors, older adults show
      significant source memory impairments. The mnemonic processes used to integrate
      contextual source information with item memory during encoding may fail to
      initiate due to the amount of effort required to encode the olfactory stimulus.
      The difficulty of encoding and subsequently retrieving the source may be
      increased due to the difficulty of encoding the odors. The results demonstrate
      the robust effects of aging on source memory for odors.

PMID- 18340104
TI  - Availability of CT and MR for assessing patients with acute stroke.

PMID- 18340105
TI  - Reversible posterior encephalopathy syndrome followed by MR angiography
      documented cerebral vasospasm in preeclampsia-eclampsia: report of 2 cases.

PMID- 18340106
TI  - A case of presumed granulomatous carotid stenosis.

PMID- 18340107
TI  - Dural carotid-cavernous fistula: relationship between evolution of clinical
      symptoms and venous drainage changes.

PMID- 18340108
TI  - Characterization of everyday functioning in mild cognitive impairment: a direct
      assessment approach.
AB  - AIMS: To evaluate the degree and pattern of functional difficulties in mild
      cognitive impairment (MCI) via direct observation of everyday task performance.
      METHODS: MCI (n = 25), mild Alzheimer's disease (AD; n = 25), and control (n =
      18) participants performed three everyday tasks of increasing complexity.
      RESULTS: Although caregivers reported no functional difficulties in MCI, direct
      observation measures of overall impairment and total errors showed MCI
      participants performed worse than controls, but better than AD participants, even
      on simple tasks. MCI and control participants exhibited significantly more
      difficulty performing steps accurately (i.e. commission errors) than completing
      task steps (i.e. omission errors), but AD participants showed an even
      distribution of commissions and omissions. CONCLUSIONS: Diagnostic criteria for
      MCI should specify mild functional deficits due to the inefficient and imprecise
      execution of task steps. Functional deficits characterized by omission of major
      task segments may indicate a diagnosis of dementia.

PMID- 18340109
TI  - Analysis of UBQLN1 variants in a Polish Alzheimer's disease patient: control
      series.
AB  - Late-onset Alzheimer's disease (LOAD) is the most common neurodegenerative
      disorder, and has a complex etiology. Recently an intronic polymorphism in the
      ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be
      associated with LOAD. We investigated whether variants in UBQLN1 confer a risk
      for the disease in 407 Polish LOAD patients and 407 controls. We observed a weak
      association with the rs2781002 polymorphism, however, contrary to the initial
      reports, in our group the association was with the A allele. Risk estimation for
      AA versus GG genotypes showed that the AA genotype is a weak risk factor for AD
      (OR = 1.8, 95% CI = 1.1-3.1, p = 0.025). This effect was stronger in a group of
      LOAD patients without APOE4 allele. Haplotype analyses indicate that there is an
      increase of haplotypes with an A allele in the case group. Also, the specific
      haplotypes with the A allele that increase AD risk differ between the APOE4
      positive and APOE4-negative pools. However, the association observed seems to be
      driven mostly by rare (<5%) haplotypes. Results suggest a need for additional
      association studies and in silico analysis of the UBQLN1 locus.

PMID- 18340110
TI  - Automatic quantification of speech intelligibility of adults with oral squamous
      cell carcinoma.
AB  - OBJECTIVE: It has been the aim of the present study to introduce a novel
      automatic technique for the objective and quantitative assessment of speech
      intelligibility to the evaluation of postoperative outcome. PATIENTS AND METHODS:
      Forty-six patients with oral carcinomas, mean age 59.8 +/- 10.1 years, and an age
      matched control group of 40 subjects without oral diseases. Recordings of a
      standard text read by the patients and the control group were analyzed by an
      automatic speech recognition system. RESULTS: For the patients, automatic speech
      recognition yielded word recognition rates between 8 and 82% (mean 49 +/- 19%),
      for the control group between 60 and 91% (76 +/- 7%). Automatic evaluation
      closely correlated with the experts' perceptual evaluation of intelligibility (r
      = -0.93; p < 0.01). The multi-rater kappa of the experts alone (0.55) differed
      only slightly from the multi-rater kappa of the experts and the speech
      recognition system (0.58). CONCLUSION: For adults with speech disorders,
      automatic speech recognition may serve as a valuable tool to assess global speech
      outcome after treatment of oral squamous cell carcinoma objectively and
      quantitatively for clinical and research purposes.

PMID- 18340111
TI  - Human cytomegalovirus controls a new autophagy-dependent cellular antiviral
      defense mechanism.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that remains the major
      infectious cause of birth defects, as well as being an important opportunistic
      pathogen. Macroautophagy (hereafter referred to as autophagy) is an
      evolutionarily conserved process responsible for the degradation of cytoplasmic
      macromolecules, and the elimination of damaged organelles via a lysosomal
      pathway. This process is also triggered in organisms by stressful conditions and
      by certain diseases. Previous observations have suggested that autophagy (also
      known as xenophagy in this case) may contribute to innate immunity against viral
      infections. Recent studies on HSV-1, another herpesvirus, have shown that HSV-1
      is able to avoid this cellular defense by means of a viral protein, ICP34.5,
      which antagonizes the host autophagy response. However, it was not known whether
      HCMV was also able to counteract autophagy. Here, we show that HCMV infection
      drastically inhibits autophagosome formation in primary human fibroblasts.
      Autophagy was assessed by GFP-LC3 redistribution, LC3-II and p62 accumulation and
      electron microscopy. Inhibition of autophagy occurred early in the infection by a
      mechanism involving viral protein(s). Indeed, only infected cells expressing
      viral proteins displayed a striking decrease of autophagy; whereas bystander, non
      infected cells displayed a level of autophagy similar to that of control cells.
      HCMV activated the mTOR signaling pathway, and rendered infected cells resistant
      to rapamycin-induced autophagy. Moreover, infected cells also became resistant to
      the stimulation of autophagy by lithium chloride, an mTOR-independent inducer of
      autophagy. These findings suggest that HCMV has developed efficient strategies
      for blocking the induction of autophagy during infection.

PMID- 18340112
TI  - A chemotherapy-associated senescence bystander effect in breast cancer cells.
AB  - A bystander effect typically refers to the death, altered growth or damage of
      cells that have not directly received chemotherapy or irradiation. Cancer cells
      derived from solid tumors readily undergo senescence in response to
      chemotherapeutic agents, prompting us to test for the existence of a senescence
      bystander effect. MCF-7 breast cancer cells were acutely exposed to Adriamycin to
      trigger senescence. Naive MCF-7 cells, when cultured in conditioned media from
      senescent breast cancer cells, growth arrested despite mitogenic stimulation and
      exhibited SA-beta-galactosidase activity, an enlarged cell size and stable
      upregulation of p21(WAF1) protein, collectively indicating a senescent state. In
      contrast, HCT-116 colon cancer cells, which also undergo p53-mediated senescence
      in response to acute AdR, did not undergo growth inhibition or senescence when
      cultured with conditioned media from senescent HCT-116 cells. Reciprocal
      experiments indicated that naive HCT-116 cells, like MCF-7 cells, are susceptible
      to the growth inhibitory effects of a breast cancer-derived mediator, which is
      independent of residual drug in conditioned media. Our study reveals a novel
      action of Adriamycin, which may contribute to its potent anti-breast cancer
      activity and lead to the discovery of additional therapeutic targets for the
      exploitation of a senescence bystander effect.

PMID- 18340113
TI  - Altered expression of cell proliferation-related and interferon-stimulated genes
      in colon cancer cells resistant to SN38.
AB  - Irinotecan is a topoisomerase I inhibitor widely used as an anticancer agent in
      the treatment of metastatic colon cancer. However, its efficacy is often limited
      by the development of resistance. We have isolated a colon carcinoma cell line,
      HCT116-SN6, which displays a 6-fold higher resistance to SN38, the active
      metabolite of irinotecan. In this paper, we studied the molecular mechanisms that
      cause resistance to SN38 in the HCT116-SN6 cell line. First, we analyzed
      proliferation, cell cycle distribution, apoptosis, topoisomerase I expression and
      activity in SN38-resistant (HCT116-SN6) and sensitive (HCT116-s cells). We showed
      that the SN38-induced apoptosis and the SN38-activated cell cycle checkpoints
      leading to G(2)/M cell cycle arrest were similar in both cell lines.
      Topoisomerase I expression and catalytic activity were also unchanged. Then, we
      compared mRNA expression profiles in the two cell lines using the Affymetrix
      Human Genome GeneChip arrays U133A and B. Microarray analysis showed that among
      the genes, which were differentially expressed in HCT116-s and HCT116-SN6 cells,
      27% were related to cell proliferation suggesting that proliferation might be the
      main target in the development of resistance to SN38. This result correlates with
      the phenotypic observation of a reduced growth rate in HCT116-SN6 resistant
      cells. Furthermore, 29% of the overexpressed genes were Interferon Stimulated
      Genes and we demonstrate that their overexpression is, at least partially, due to
      endogenous activation of the p38 MAP kinase pathway in SN38 resistant cells. In
      conclusion, a slower cell proliferation rate may be a major cause of acquired
      resistance to SN38 via a reduction of cell cycle progression through the S phase
      which is mandatory for the cytotoxic action of SN38. This lower growth rate could
      be due to the endogenous activation of p38.

PMID- 18340114
TI  - C. elegans as a model organism for in vivo screening in cancer: effects of human
      c-Met in lung cancer affect C. elegans vulva phenotypes.
AB  - Cancers typically harbour several mutant forms of key cellular genes that
      contribute to its complex phenotype. Our lab has previously identified gain-of
      function mutations in some of the receptor tyrosine kinases such as c-Met in lung
      cancer. In order to investigate the mutant gene in the context of a whole
      organism, the current choice of in vivo model is limited to the mouse. To rapidly
      screen the functional aspects of mutant forms of c-Met detected in lung cancer,
      we used the nematode C. elegans as the model organism. Transgenic worms were
      generated that harbour wild type or the frequently seen mutant forms of c-Met in
      lung cancer (c-MetR988C and c-MetT1010I). Expression of the mutant human c-Met
      forms in C. elegans consistently resulted in significantly low fecundity and
      abnormal vulval development characterized by hyperplasia. Interestingly, exposure
      of c-Met mutant transgenic worms to nicotine resulted in enhanced abnormal vulval
      development, fecundity and locomotion. Our studies provide first evidence that
      human c-Met mutations can be studied in C. elegans, and that carcinogens can
      enhance mutant c-Met function expressed in C. elegans transgenic animals. We
      therefore propose the use of C. elegans as a model to rapidly assess the role of
      cancer specific gene mutations in the context of a whole organism.

PMID- 18340115
TI  - Static magnetic fields induce blood flow decrease and platelet adherence in tumor
      microvessels.
AB  - Red blood cell flow in capillaries is reduced during exposure to strong static
      magnetic fields (SMFs). Intratumoral microcirculation is characterized by
      tortuous microvessels with chaotic architecture and by irregular, sluggish blood
      flow with unstable rheology. It was the aim of this study to analyze SMF exposure
      effects on tumor microcirculation with regard to interactions of corpuscular
      blood components with tumor microvessel walls. In vivo fluorescence microscopy
      was performed in A-Mel-3 tumors growing in dorsal skinfold chamber preparations
      of Syrian Golden hamsters. SMFs with varying field strength (< 600 mT) were
      generated by changing the distance between a strong NdFeB rod magnet and the
      tissue region of interest. Short-time exposure above a magnetic flux density of
      about 150 mT resulted in a significant reduction of red blood cell velocity
      (vRBC) and segmental blood flow in tumor microvessels. At the maximum strength of
      587 mT, a reversible reduction of vRBC (approximately 40%) and of functional
      vessel densitiy (approximately 15%) was observed. Prolongation of the exposure
      time from 1 min to up to 3 h resulted in comparable reductions. Microvessel
      diameters and leukocyte-endothelial cell interactions remained unaffected by SMF
      exposure. However, in contrast to tumor-free striated muscle controls, exposure
      at the maximum flux density induced a significant increase in platelet
      endothelial cell adherence in a time-dependent manner that was reversible after
      reducing SMF strength. These reversible changes may have implications for
      functional measurements of tumor microcirculation by MRI and new therapeutic
      strategies using strong SMFs.

PMID- 18340116
TI  - A small molecule that disrupts Mdm2-p53 binding activates p53, induces apoptosis
      and sensitizes lung cancer cells to chemotherapy.
AB  - Mdm2 binds to p53 and promotes its degradation. A class of small molecule Mdm2
      inhibitors (MI) was recently discovered that binds to Mdm2 and disrupts Mdm2-p53
      binding. The efficacy of MI-43 was tested against two pairs of human lung cancer
      lines differing in p53 status: adenocarcinoma A549 (p53 wild-type, wt) and H522
      (p53-null) and non-small cell lung carcinoma H460 (p53wt) and H1299 (p53-null).
      MI-43 induced the accumulation of p53 and its downstream target genes, Mdm2, p21,
      Noxa and Puma only in wt p53-containing cells, indicating that disruption of Mdm2
      p53 binding increases p53, which is transcriptionally active. MI-43
      preferentially inhibited the growth of wt p53-containing cells in a p53 dependent
      manner, but was much less effective in p53-null cells. Mechanistically, MI-43
      induced G(1) or G(2) arrest at low concentration as result of p21 induction, and
      apoptosis at high concentration due to Puma/Noxa induction. Importantly, MI-43 is
      much less toxic to normal fetal lung fibroblast, MRC5 cells. Finally, when used
      in combination, MI-43 sensitized chemo-resistant A549 cells to etoposide-induced
      apoptosis. Thus, MI-43 or its analogues could be further developed as a novel
      class of anticancer drug for lung cancer cells harboring wt p53 as a single agent
      or in combination with chemo-drugs.

PMID- 18340117
TI  - Influence of IFNgamma co-expression on the safety and antiviral efficacy of
      recombinant fowlpox virus HIV therapeutic vaccines following interruption of
      antiretroviral therapy.
AB  - Therapeutic immunization to stimulate host immune responses and control human
      immunodeficiency virus (HIV-1) replication is being investigated as a
      supplementary treatment for the management of HIV infection. On completion of an
      earlier study involving three vaccinations while taking combination
      antiretroviral therapy (CART), twenty-five subjects with plasma viral load (pVL)
      <50 copies/mL received a booster vaccination with either placebo (n = 7); fowl
      pox vaccine (rFPV) expressing HIV-1 Gag/Pol; [partial construct- PC (n = 8)] or
      rFPV coexpressing HIV-1 Gag/Pol and human interferon gamma[full construct - FC (n
      = 10)]. One week after the booster vaccination, participants stopped ART and were
      monitored for safety, pVL and immunological parameters for < or =20 weeks. The
      time weighted mean change (SD) from baseline plasma HIV RNA was 1.80 (0.72), 1.78
      (0.91) and 0.96 (0.91) log(10) copies/mL for placebo, PC and FC recipients
      respectively (p = 0.06; mean differences between placebo and FC). Laboratory
      evaluations did not reveal differences in anti-HIV specific immune responses
      between study arms. No difference between treatment arms for host genetic factors
      known to affect pVL was demonstrated. In conclusion, vaccination with FC was
      associated with a trend toward lower rates of HIV replication following cessation
      of ART relative to placebo or PC. The promising antiretrovirological effect
      supports further study of FC in a larger trial with a broader population of
      patients with HIV disease.

PMID- 18340118
TI  - The changing epidemiology of severe cytomegalovirus disease in Australia.
AB  - Few studies have reported the epidemiological characteristics and burden of
      severe cytomegalovirus (CMV) in the hospital setting. This study used data
      compiled by the Australian Institute of Health and Wealthfare(1) to examine the
      trends in hospital admissions due to CMV in different patient groups. As CMV
      disease mainly occurs in high-risk populations and almost always results in
      hospitalization, hospital data are an appropriate source of information on the
      epidemiology of clinically relevant disease. The study found that between 1993
      and 2001 the average annual rate of hospital admissions where CMV was identified
      as the principal reason for admission amounted to 14.2 cases per 100,000
      populations. This rate varied between 21.6 (1993/94) and 2.0 (2000/01) per
      100,000 per year, and was always somewhat higher for men compared to women. The
      average annual incidence of children admitted to hospital with congenital CMV
      (principal and secondary diagnosis) in children aged 0-4, 5-9 and 10-14 years was
      1.4, 1.3 and 0.4 per 100,000 respectively. Correlations with Human
      Immunodeficiency Virus (HIV), organ transplantation and other causes of immuno
      suppression were also examined. The burden of severe CMV disease in Australia was
      found to be significant and comparable to other diseases for which national
      vaccination programs exist. As new vaccines for CMV may soon be available,
      understanding the pre-vaccination burden of CMV disease is useful for planning a
      vaccination program should a suitable vaccine be developed.

PMID- 18340119
TI  - Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) acute
      coronary syndromes Critical Pathway Toolkit.
AB  - The Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE)
      program has developed an acute coronary syndromes (ACS) Critical Pathways Toolkit
      to facilitate understanding and adoption of the new American College of
      Cardiology/American Heart Association Guidelines. This review provides many
      different types of tools, including pathway documents, pocket cards, standardized
      order sets, posters, and personal digital assistant programs, all aimed to
      improve the quality of care provided to patients with ACS. It is hoped that the
      availability of these materials will help physicians, nurses, and hospitals
      implement the new guidelines and thus improve outcomes for patients with ACS.

PMID- 18340120
TI  - Anticoagulation management strategies in patients with atrial fibrillation.

PMID- 18340121
TI  - PROVE-IT TIMI 22 Study: potential effects on critical pathways for acute coronary
      syndrome.

PMID- 18340122
TI  - Hospital performance with myocardial reperfusion therapy: are hospitals capable
      of meeting established guidelines?
AB  - OBJECTIVES: To determine whether hospitals are capable of delivering myocardial
      reperfusion therapy in a manner consistent with the American College of
      Cardiology/American Heart Association guidelines. DATA SOURCE AND STUDY SETTING:
      Data from the National Registry of Myocardial Infarction (NRMI)-2 and NRMI-3 were
      used. NRMI is an observational study, sponsored by Genentech, conducted from June
      1994 through June 2000 and involving 1876 hospitals and 1,310,030 patients across
      the United States. The protocol calls for collecting data on all patients with a
      diagnosis of acute myocardial infarction. The setting was community and tertiary
      hospitals in the United States. STUDY DESIGN: This observational study used
      process capability analysis. PRINCIPAL FINDINGS: Overall, no hospital was deemed
      capable of delivering myocardial reperfusion therapy consistent with the American
      College of Cardiology/American Heart Association guidelines. The highest
      thrombolytic and angioplasty CPUs were 0.44 and 0.52, respectively-well below the
      traditional value of 1.0 signifying minimum capability. In addition, among the
      hospitals examined, there remained a wide degree of variability in process
      capability, ranging from -0.69 to 0.52. CONCLUSIONS: Myocardial reperfusion
      therapy performance measurement systems relying solely on mean time-to
      reperfusion conceal true process performance, thereby obscuring quality
      improvement opportunities and strategies for improvement. Health care providers,
      purchasers, regulators, and other organizations interested in measuring and
      improving health care quality are encouraged to incorporate process capability
      analysis into their myocardial reperfusion therapy performance measurement and
      quality management systems.

PMID- 18340123
TI  - Emergency department observation unit management of heart failure.
AB  - The United States is currently in the midst of a heart failure (HF) epidemic. All
      predictions suggest that this will increase in both scope and impact.
      Consequently new methods to improve the clinical outcomes and financial
      consequences for HF treatment are needed. This manuscript reviews the potential
      of Emergency Department Observation to improve care for the decompensated HF
      patient. Suggested clinical pathways, order sheets, and the potential for
      improved outcomes are presented.

PMID- 18340124
TI  - Comment on "Emergency observation unit management of heart failure".

PMID- 18340125
TI  - Improvement in clinical outcomes in acute coronary syndromes after the
      implementation of a critical pathway.
AB  - Although several advances have been made in the management of acute coronary
      syndromes, the adoption of such measures in clinical practice has been
      suboptimal. The implementation of critical pathways has been suggested as a
      strategy to improve clinical effectiveness, although its effect is still to be
      demonstrated. The objective was to evaluate the impact of a critical pathway on
      the process of care of patients admitted with acute coronary syndromes in a
      teaching hospital. In a prospective cohort study, patients 30 years or older
      admitted to the emergency department with suspected acute coronary syndromes were
      evaluated. Primary outcomes were major cardiovascular events, percutaneous
      coronary intervention, and in-hospital mortality during 1 semester before and 4
      semesters after implementation of the pathway. Multivariate logistic regression
      analysis was used to adjust for differences between the periods studied and to
      identify predictors of poor prognosis. Of the 1003 patients evaluated, 150 (15%)
      had myocardial infarction, and 240 (24%) had unstable angina. There was no
      difference in clinical characteristics and risk assessment in the periods
      evaluated. Overall, the quality of care improved after the pathway, with a
      significant decrease in complication and mortality rates in the last 2 years. In
      multivariate analysis, patients admitted in the last semester showed fewer major
      cardiovascular events (odds ratio = 0.74; P = 0.02) and more percutaneous
      coronary intervention (odds ratio = 1.3; P = 0.03). The implementation of a
      critical pathway may have a positive impact on the quality of care of patients
      with acute coronary syndromes. Further studies are needed to evaluate better this
      and other initiatives aimed at maximizing clinical effectiveness.

PMID- 18340126
TI  - Controversies surrounding the use of glycoprotein IIb/IIIa inhibitors.
AB  - The use of glycoprotein IIb/IIIa inhibitors reduces morbidity and mortality in
      patients with acute coronary syndromes and patients undergoing percutaneous
      coronary intervention. Despite the sound body of evidence that supports the use
      of these agents, registry data indicate that there is substantial underuse in
      eligible patients. This may be due to their modest treatment effect, controversy
      over the significance of reductions in recurrent myocardial infarction, or
      confusion over appropriate combinations of antiplatelet and antithrombin agents.
      The challenge for clinicians is to identify patients that receive the most
      benefit from the use of glycoprotein IIb/IIIa inhibitors. Until the results of
      ongoing trials become available, the American College of Cardiology/American
      Heart Association guidelines provide reasonable recommendations on the use of
      these agents in clinical practice.

PMID- 18340127
TI  - Role of beta-blocker therapy in the postmyocardial infarction patient with and
      without left ventricular dysfunction consensus guideline.

PMID- 18340128
TI  - Venous Thromboembolism Guidebook, fourth edition.

PMID- 18340129
TI  - Probability stratification and systematic diagnostic approach for chest pain
      patients in the emergency department.
AB  - Management of chest pain patients in the emergency department has been a dilemma
      because of difficulty in identifying those who can be immediately discharged and
      those who need to be hospitalized. We assessed the efficacy of a probability
      stratification model and a systematic diagnostic strategy in 1003 consecutive
      chest pain patients prospectively evaluated and stratified for acute coronary
      syndromes according to chest pain characteristics and admission
      electrocardiogram. Patients with no suspicion of acute coronary syndromes (n =
      224) were immediately discharged, whereas those with very-high probability (n
      =119) were admitted to the coronary care unit. Remaining patients were evaluated
      in a Chest Pain Unit and investigated during a 9-hour period (intermediate
      probability, n = 433) (route 2) and a 6-hour period (low-probability, n = 277)
      (route 3). Sensitivity and negative predictive value of chest pain type for the
      diagnosis of acute myocardial infarction (94% and 97%, respectively) was much
      better than the admission electrocardiogram (49% and 86%, respectively) and
      admission creatine kinase-MB (46% and 86%, respectively). Serial creatine kinase
      MB determinations ruled out acute myocardial infarction by the third-hour
      postadmission in all route 3 patients but only at the ninth-hour in route 2
      patients. For patients with no ST-segment elevation, chest pain type was the
      strongest independent predictor of acute coronary syndromes. It is concluded that
      chest pain type is the best single diagnostic tool to rule in/out acute coronary
      syndromes on admission to the emergency department. Patients with suspicious
      chest pain must have serum creatine kinase-MB measurements up to 9 hours
      postadmission to rule out acute myocardial infarction.

PMID- 18340130
TI  - The role of an emergency department observation unit in a clinical pathway for
      atrial fibrillation.

PMID- 18340131
TI  - Comment on "The role of an emergency department observation unit in a clinical
      pathway for atrial fibrillation".

PMID- 18340132
TI  - The chest pain center as an operational model.
AB  - The purposes of this paper are to establish the acute coronary syndrome as a
      pathophysiologic model, to establish the Chest Pain Center model as a
      complementary operational model that can be employed by a wide range of hospitals
      that seek to improve the process of care related to acute coronary syndromes, to
      differentiate process improvement versus performance improvement, and to
      establish the individual facility as the nidus for the improvement process.

PMID- 18340133
TI  - Comment on "Improving the process of care related to acute coronary syndrome as
      distinguished from performance improvement".

PMID- 18340134
TI  - The PAIN pathway as a tool to bridge the gap between evidence and management of
      acute coronary syndrome.
AB  - Clinical guidelines on the management of Acute Coronary Syndrome (ACS) have
      consistently shown a major gap between the guidelines and their application in
      the actual management of ACS. In an attempt to achieve the goal of bridging the
      gap between these evidence-based guidelines and patient management, we have
      reorganized the pathway for the management of ACS at our institution. The pathway
      has been designated with the acronym of PAIN (Priority risk, Advanced risk,
      Intermediate risk, and Negative/Low risk), to reflect patients risk
      stratification upon admission. Along with the pathway comes a single detailed
      order sheet and a single discharge form which are color-coded according to the
      patient's risk stratification.This model is designed to mandate and, thus,
      markedly improve adherence to the published American Heart Association/American
      College of Cardiology guidelines for the management of ACS.

PMID- 18340135
TI  - Detecting patients with acute coronary syndrome in the chest pain center of the
      emergency department with cardiac magnetic resonance imaging.
AB  - Managing patients with chest pain in the Emergency Department (ED) remains a
      challenge where advanced imaging technology may play a role. Detecting acute
      coronary syndrome in the emergency department with cardiac magnetic resonance
      imaging (MRI) was studied in 161 consecutive chest pain patients in a prospective
      observational study. Patients with ST elevation myocardial infarction were
      excluded from study participation. All patients underwent MRI study when
      hemodynamically stable, free of ongoing chest pain, and within 12 hours of
      symptoms onset. The MRI study takes an average of 38 +/- 12 minutes and included
      global and regional left ventricular function, myocardial perfusion, and
      gadolinium-enhanced myocardial infarction detection. The sensitivity and
      specificity for detecting acute coronary syndrome was 84% and 85% by MRI. The MRI
      was more sensitive than strict electrocardiogram (ECG) criteria for ischemia (P <
      0.001) and peak troponin-I (P < 0.001). The MRI was more specific than an
      abnormal ECG (P < 0.001). Multivariate logistic regression analysis showed MRI
      was the strongest predictor of acute coronary syndrome and added diagnostic value
      over clinical parameters (P < 0.001). A nonstress cardiac MRI performed in this
      urgent clinical setting is safe and exhibited diagnostic operating
      characteristics suitable for triage of patients with chest pain in the emergency
      department. MRI accurately detected a high fraction of patients with acute
      coronary syndrome including patients with enzyme negative unstable angina.

PMID- 18340136
TI  - Comment on "Detecting patients with acute coronary syndrome in the chest pain
      center of the emergency department with cardiac magnetic resonance imaging".

PMID- 18340137
TI  - Selective use of bivalirudin to reduce post-PCI vascular complications.

PMID- 18340139
TI  - Accreditation of chest pain centers.

PMID- 18340138
TI  - Implementing clinical pathways for patients admitted to a medical service:
      lessons learned.
AB  - In an attempt to improve quality of care for patients admitted to our medical
      service we have implemented the use of pathways. These are printed standards of
      care and a mechanism for daily multidisciplinary documentation. The goals of our
      pathways are to: improve quality using printed standards of care; improve
      documentation of the care delivered; improve communication about daily goals
      between all team members, patients and families; standardize our in-patient chart
      format throughout the hospital; and increase efficiency of care. Pathways were
      designed to provide physicians and nurses with the standards for care and provide
      a mechanism for multidisciplinary documentation on our in-patient charts. We now
      have 2 pathways in use on our medical service. One is a clinical care plan (CCP)
      and the other is a Pancreatitis Pathway (PP) for patients admitted with acute
      pancreatitis and the other a guideline for care for all patients. The pathways
      were developed by teams including attending physicians (General Internists and
      Gastroenterologists), medicine house officers, nurses, and care coordinators. The
      pathways are used for all patients admitted to our medical service if they are
      admitted to one of 2 floors. This paper includes a comparison of outcomes for our
      first 9 patients who were managed using the pancreatitis pathway versus 7
      patients cared for without the pathway. Significant differences in the
      pancreatitis pathway treated patients included: 1) less intense pain on day 2, (P
      = 0.04); 2) less pain on day of refeeding (P = 0.004); and 3) less IV fluids
      administered (P = 0.05). We also describe several lessons we have learned about
      using pathways for in-patients on a medical service in an academic medical
      center. We have learned the following lessons. Nursing documentation is improved.
      Physicians need ongoing encouragement and education about the value of pathways.
      There is considerable work involved for unit coordinators, care coordinators, and
      nursing in using pathways on a medical-surgical floor. There must be physician
      and nurse champions. There must be ongoing feedback to users. There must be input
      from users and edits. We believe the use of pathways as a process to remind
      clinicians of quality standards will improve the care of our patients by
      decreasing variation, improving team communication, and enhancing patient and
      family education.

PMID- 18340140
TI  - Implications of the mechanical (PCI) vs thrombolytic controversy for ST segment
      elevation myocardial infarction on the organization of emergency medical
      services: the Boston EMS experience.
AB  - With the many advances in rapid reperfusion therapy for management of acute ST
      segment elevation myocardial infarction (STEMI), there is a need to revisit the
      current plan for prehospital triage (point of entry). Until recently in Boston,
      and nationwide, there has been a policy that patients with suspected acute MI
      were brought to the nearest hospital. Then, if ST segment elevation was present,
      patients were treated with either thrombolytic therapy or primary percutaneous
      coronary intervention (PCI). Recent data, however, have shown that with advances
      in interventional devices, techniques and institutional experience, primary PCI
      is associated with improved outcomes compared with thrombolytic therapy for all
      patients with STEMI when provided at expert centers with high institutional
      volumes, with experienced interventional cardiologists as the operators, and with
      relatively short time to treatment. We describe the rationale for and the
      implementation of the Boston EMS STEMI Triage Plan and Treatment Registry. Many
      of the issues that prompted the implementation of the Boston STEMI plan are
      relevant to all EMS systems. Among these issues are the accuracy of prehospital
      identification of STEMI patients, the availability of mechanical reperfusion
      therapy, the appropriate triage of patients with complicated myocardial
      infarction or shock, as well as the local consensus regarding strength of the
      evidence favoring mechanical reperfusion. This article describes the history of
      the Boston EMS STEMI Triage Plan and Treatment Registry and suggests the need for
      other EMS systems to develop a systematic approach to patients with STEMI.

PMID- 18340141
TI  - Perioperative use of beta-blocker in noncardiac surgery: a multicenter
      educational intervention to achieve best practice guidelines.
AB  - Perioperative cardiac ischemia and infarction are important causes of morbidity
      and mortality in patients undergoing noncardiac surgery. There is now significant
      evidence that the use of prophylactic beta-adrenergic antagonists among selected
      patients at risk for perioperative cardiovascular complications is associated
      with a reduction in myocardial ischemia and cardiac events. Furthermore,
      consensus guidelines have incorporated the findings of recent studies and provide
      recommendations for the appropriate utilization of beta-adrenergic antagonists
      among selected patients. Despite these guidelines, it is unknown to what extent
      these recommendations have become translated into clinical practice. After
      measuring perioperative beta-blocker use among participating hospitals within the
      New York Presbyterian Health Network, we developed a multicenter educational
      intervention to improve the overall utilization of beta-adrenergic prophylactic
      therapy in accordance with best practice guidelines. The literature supporting
      the development of this intervention is presented in this paper, along with the
      tools that are currently being used for decision support across an academic
      healthcare network.

PMID- 18340142
TI  - ST elevation MI admission orders: Harbor-UCLA Medical Center.

PMID- 18340143
TI  - Accuracy of a neural diagnostic tree for the identification of acute coronary
      syndrome in patients with chest pain and no ST-segment elevation.
AB  - Identifying acute coronary syndrome is a difficult task in the emergency
      department because symptoms may be atypical and the electrocardiogram has low
      sensitivity. In this prospective cohort study done in a tertiary community
      emergency hospital, we developed and tested a neural diagnostic tree in 566
      consecutive patients with chest pain and no ST-segment elevation for the
      diagnosis of acute coronary syndrome. Multivariate regression and recursive
      partitioning analysis allowed the construction of decision rules and of a neural
      tree for the diagnosis of acute myocardial infarction and acute coronary
      syndrome. Predictive variables of acute coronary syndrome were: age > or =60
      years (odds ratio [OR] = 2.3; P = 0.0016), previous history of coronary artery
      disease (OR = 2.9; P = 0.0008), diabetes (OR = 2.8; P = 0.0240),
      definite/probable angina-type chest pain (OR = 17.3; P = 0.0000) and ischemic
      electrocardiogram (ECG) changes on admission (OR = 3.5; P = 0.0002). The receiver
      operating characteristic curve of possible diagnostic decision rules of the
      regression model disclosed a C-index of 0.904 (95% confidence interval = 0.878 to
      0.930) for acute coronary syndrome and 0.803 (95% confidence interval 0.757 to
      0.849) for acute myocardial infarction. For both disorders, sensitivities of the
      neural tree were 99% and 93%, respectively, and negative predictive values were
      both 98%. Negative likelihood ratios were 0.02 and 0.1, respectively. It is
      concluded that this simple and easy-to-use neural diagnostic tree was very
      accurate in the identification of non-ST segment elevation chest pain patients
      without acute coronary syndrome. Patients identified as low probability of
      disease could receive immediate stress testing and be discharged if the test is
      negative.

PMID- 18340144
TI  - Change of care for patients with acute myocardial infarctions through algorithm
      and standardized physician order sets.
AB  - OBJECTIVE: To determine whether there was a difference in patient care for
      patients with acute myocardial infarction, when physicians had a choice of using
      standardized orders or de novo orders for acute coronary syndrome (ACS). In both
      instances, the physician had available an algorithm developed using the American
      Heart Association/American College of Cardiology (AHA/ACC) guidelines for ACS.
      METHODS: This was a retrospective study where hospital charts were reviewed that
      had the primary diagnosis of acute myocardial infarction (including segment
      elevation myocardial infarction (STEMI) and non-segment elevation myocardial
      infarction (NSTEMI). Charts were reviewed to assess medications ordered within
      the first 24 hours of hospitalization. These medications included aspirin, beta
      blockers, angiotensin-converting enzyme inhibitors (ACE inhibitors), I.V.
      unfractionated heparin therapy or subcutaneous low-molecular-weight heparin
      (enoxaparin or Lovenox), I.V. tenecteplase, or I.V. eptifibatide. Other patient
      care items were also reviewed: cardiac rehabilitation and cardiovascular medicine
      consultation. Finally, discharge medications were reviewed. RESULTS: Patients
      were more likely to receive aspirin, beta-blockers, and ACE inhibitor therapy
      when standardized (preprinted) orders were used as opposed to de novo orders
      constructed by the physicians for that particular admission. For those patients
      with STEMI, all received I.V. reperfusion therapy (I.V. tenecteplase), when
      standardized orders were used. This was not nearly the case when de novo orders
      were written by the physician. The same finding prevailed for the use of I.V.
      eptifibatide in the NSTEMI patients, when standardized orders were compared with
      de novo order sheets. Cardiac rehabilitation (phase I) was ordered more
      frequently in the patient subset that had the initiation of therapy with the
      standardized orders compared with the de novo orders. A perplexing issue did
      arise on review of discharge medications. Those patients who had their care
      initiated with standardized orders were less likely to go home on their
      hospitalization medications (aspirin, beta-blockers, and ACE inhibitors) than
      those patient that had their hospital care initiated with the de novo orders.
      CONCLUSION: A higher percentage of patients whose physicians initiated hospital
      therapy with standardized order sheets, which follow AHA/ACC guidelines, received
      appropriate medications in a timely fashion. This was not necessarily the case on
      review of the discharge medications. Without having standardized discharge
      orders; those patients whose care was initiated by standardized orders were less
      likely to be discharged on aspirin, beta-blockers, or ACE inhibitors. On further
      investigation, it was discovered that physicians who used standardized orders
      assumed the patient was discharged on the same medication they received in the
      hospital. After realization of this, the order sheet is being revised to include
      this part of patient care.

PMID- 18340145
TI  - Risk stratification and the management of non-ST-segment elevation acute coronary
      syndromes: the role of antiplatelet therapy.
AB  - Risk stratification is crucial in guiding the acute management of non-ST-segment
      elevation (NSTE) acute coronary syndromes (ACS). An early invasive strategy
      (catheterization/revascularization) in conjunction with aggressive antiplatelet
      and anticoagulant therapy offers the most effective means of reducing ischemic
      complications in intermediate- and high-risk patients. In low-risk patients,
      stress testing serves to indicate whether a secondary prevention strategy or
      elective catheterization/percutaneous coronary intervention and GP IIb/IIIa
      inhibition is more appropriate. NSTE ACS also confers a long-term risk of
      recurrent cardiovascular events, regardless of whether initial management follows
      a medical or interventional approach. Combination aspirin and clopidogrel therapy
      is effective for secondary prevention across the spectrum of NSTE ACS patients,
      regardless of risk or initial treatment strategy (conservative or invasive). Long
      term aspirin and clopidogrel therapy addresses the thrombotic component of
      atherothrombosis, while combined beta-blocker, ACE inhibitor, and statin therapy
      is directed against the atheroma.

PMID- 18340147
TI  - Future noninvasive evaluation of chest pain patients in the observation unit of
      the chest pain center.

PMID- 18340146
TI  - The use of CTA in the chest pain center: a perspective.
AB  - Suitable imaging methods to reliably rule out coronary artery disease as the
      underlying condition might be beneficially applied in the workup of patients with
      acute chest pain. The temporal and spatial resolution of computed tomgraphy and
      electron beam computed tomography has seen continuous improvements over the past
      years. Current scanner generations permit relatively reliable visualization of
      the coronary arteries and several studies have demonstrated a high negative
      predictive value to rule out coronary artery stenoses. Even though applications
      in the context of acute coronary syndromes have not yet been specifically
      evaluated, it seems likely that computed tomography imaging may develop into a
      tool that can be integrated into the workflow in chest pain centers once
      appropriate studies have been performed.

PMID- 18340148
TI  - Greater benefit of early invasive strategy for unstable angina and non-ST
      elevation myocardial infarction in United States compared with non-United States
      patients: a TACTICS-TIMI 18 substudy.
AB  - BACKGROUND: The TACTICS-TIMI 18 (Treat Angina with Aggrastat and Determine Cost
      of Therapy with an Invasive or Conservative Strategy - Thrombolysis in Myocardial
      Infarction 18) trial compared routine invasive to conservative care for the
      management of patients with unstable angina and non ST-elevation myocardial
      infarction, and included the routine use of the platelet glycoprotein IIb/IIIa
      inhibitor tirofiban in the initial medical stabilization of all patients.
      METHODS: Because previous trials utilizing IIb/IIIa inhibition for acute coronary
      syndrome (ACS) patients have demonstrated different outcomes in non-US and US
      patients, the authors sought to determine whether differences in baseline
      characteristics and practice patterns between 1844 US and 376 non-US patients and
      physicians would affect outcomes in the TACTICS-TIMI 18 trial. Event rates were
      stratified by treatment strategy and adjusted for baseline and treatment
      differences between cohorts. RESULTS: Although US subjects were more likely
      women, hypertensive, and diabetic, the US and non-US patients did not differ with
      respect to low, intermediate, or high TIMI risk scores. For US patients, the
      primary composite end point of death, myocardial infarction (MI), and
      rehospitalization for ACS was reduced with an invasive strategy by 40% (95% CI:
      0.43-0.83) at 30 days and by 30% (95% CI: 0.55-0.88) at 180 days. Non-US patients
      managed conservatively had 35% fewer events at 180 days than their invasive
      counterparts resulting in no benefit for the invasive strategy (P = 0.016 for the
      interaction term between country and treatment group). Similar results were
      observed for the additional outcome of death and MI, and in troponin-positive
      patients. Adjustment for baseline characteristics, medications during the initial
      hospitalization, and the use of cardiac procedures suggested that a higher cross
      over rate from conservative to invasive care in non-US patients (59% versus 49%,
      P = 0.02) was the most likely explanation for the lower event rate in the
      conservatively managed patients outside the US. CONCLUSION: US patients treated
      with tirofiban and early routine cardiac catheterization had a 30% reduction in
      major cardiac events by 6 months compared with those treated with tirofiban and a
      conservative (selective invasive) approach. Non-US patients treated
      conservatively had fewer events than US patients, which appears to be related to
      a higher rate of cross-over to invasive care. These findings emphasize the
      importance of both risk stratification and invasive management for ACS patients.

PMID- 18340149
TI  - The final common pathway for community heart attack care: combining prevention
      through intervention when acute events are taking place with future prevention
      using the novel emerging cardiovascular risk factors.

PMID- 18340150
TI  - The future of cardiac markers in the emergency department.
AB  - The development of new cardiac marker strategies has the potential of improving
      the treatment and triage of patients in the emergency department with possible
      acute coronary syndrome. Although there has been a proliferation of new cardiac
      markers, at present rigorous studies demonstrating the incremental utility of
      many of these are lacking.

PMID- 18340151
TI  - Emergency department evaluation and treatment of patients with ST-segment
      elevation myocardial infarction.
AB  - Acute coronary syndrome (ACS) identifies a set of clinical presentations with a
      common etiology. This entity accounts for more deaths in the United States than
      any other disease or form of injury. Early identification and management has been
      shown to substantially reduce the morbidity and mortality associated with ACS. As
      a result of efforts by several organizations to inform the public of the
      importance of immediately responding to signs and symptoms of ACS, a growing
      percentage of ACS patients are seeking emergency department care in a timely
      manner. Patients with ST segment elevation myocardial infarction (STEMI) are
      among the most vulnerable ACS patients. Immediate triage to a properly equipped
      and staffed ACS area within the ED is essential. Some therapeutic measures can be
      implemented while the initial assessment is underway. Additional therapeutic
      interventions will be dictated by the results of history, physical examination,
      electrocardiogram, serum marker measurements, radiologic and ultrasound results.
      Protocols designed to assist with the management of STEMI patients improve the
      speed and accuracy of treatment while helping to reduce medical errors. Protocols
      should include stimuli that will encourage timely, appropriate interfacility
      transfers, personal physician involvement, and cardiology consultation. The rapid
      pace of advancement in medical knowledge surrounding STEMI management
      necessitates monitoring of compliance with protocols and periodic revision to
      achieve optimal outcomes for patients.

PMID- 18340152
TI  - Early exercise testing for risk stratification of low-risk patients in chest pain
      centers.

PMID- 18340153
TI  - Early and aggressive treatment of patients with acute ST segment elevation and
      non-ST segment elevation myocardial infarction leads to improved clinical
      outcomes.
AB  - Acute myocardial infarction remains a significant burden to our society. Despite
      being the number 1 cause of mortality, there remains no uniform approach to
      treatment, which is unlike that of the triage and care of trauma victims. It is
      now well documented that acute reperfusion therapy has a profound benefit;
      however, many current strategies take too long to be performed and thus those
      potential benefits are often reduced. The emergence of prehospital treatment as a
      means to reducing time to reperfusion provides a new avenue for earlier therapy.
      With a coordinated aggressive treatment strategy and the identification of
      primary cardiovascular centers dedicated to the treatment of ST segment elevation
      myocardial infarctions (STEMI), we believe the mortality of an STEMI can be
      significantly reduced. Similarly, the treatment of non-ST segment elevation
      myocardial infarction has shifted to an aggressive approach. Although
      thrombolytic therapy is not indicated, the use of glycoprotein IIb/IIIa
      antagonists, as well as early interventional revascularization, is the current
      preferred treatment strategy. We review important current trials that shape the
      practice of treatment as well as introduce a novel concept of combined
      prehospital administration of thrombolytics with urgent culprit artery
      revascularization.

PMID- 18340154
TI  - Act in time to heart attack signs: update on the National Heart Attack Alert
      Program's campaign to reduce patient delay.
AB  - Outcomes of reperfusion treatment for acute myocardial infarction (MI) can be
      dramatically enhanced if patients present early after symptom onset. Yet delayed
      presentation by patients with acute coronary syndrome (ACS) symptoms (including
      MI and unstable angina) remains a tenacious challenge. The "Act in Time to Heart
      Attack Signs" is a public education campaign sponsored by the National Heart,
      Lung, and Blood Institute's (NHLBI's) National Heart Attack Alert Program (NHAAP)
      that addresses early recognition and response to ACS symptoms by patients,
      providers, and the general public. The campaign's materials and messages are
      based on those used in a multicenter research program, the Rapid Early Action for
      Coronary Treatment (REACT), funded by the National Heart, Lung, and Blood
      Institute from 1994-1998. Materials are available for providers, patients, and
      the public discussing heart attack risk, common heart attack symptoms, the
      importance of seeking early care, common misconceptions about how heart attacks
      present, and the importance of accessing care by calling 9-1-1. There is a
      critical need for all healthcare providers to relay this lifesaving information
      to the patients seen in their practice settings.

PMID- 18340155
TI  - Prevention of contrast-induced nephropathy with sodium bicarbonate: an evidence
      based protocol.
AB  - Contrast-induced nephropathy has continued to plague interventional cardiology as
      an all-too-frequent complication of diagnostic and therapeutic procedures. We
      present an evidence-based protocol for prevention of this complication that uses
      infusion of NaHCO3 to effect urinary alkalinization and possibly decrease free
      radical renal injury resulting from contrast exposure.

PMID- 18340156
TI  - Updated algorithms for using B-type natriuretic peptide (BNP) levels in the
      diagnosis and management of congestive heart failure.
AB  - The growing popularity of BNP testing is a testimony to its usefulness for
      diagnosing and managing patients with congestive heart failure. The algorithms in
      this article are based on the most-up-to-date evidence-based medicine we have
      intermingled with clinical judgement of someone who has used BNP testing since
      its inception.

PMID- 18340157
TI  - A rapid-response alphanumeric paging design decreases door-to-balloon times in
      patients undergoing primary percutaneous coronary intervention for ST elevation
      acute myocardial infarction.
AB  - INTRODUCTION: In acute ST elevation myocardial infarction (STEMI), rapid
      reperfusion of the infarcted artery improves cardiovascular outcomes; however,
      many hospitals have difficulty achieving recommended times. We hypothesized that
      a Rapid-Response Alphanumeric Paging Design (RAPiD) would reduce door-to-balloon
      time for primary percutaneous coronary intervention (PCI) in STEMI. METHODS: A
      chest pain algorithm and interdisciplinary team was established in December 2000.
      In August 2002, RAPiD was instituted to transmit the diagnosis and location of a
      STEMI to the chest pain team through a speed-dial button. All patients presenting
      to our emergency department from February 2002 through July 2003 with STEMI were
      included. Exclusion criteria included lack of chest pain, cardiopulmonary arrest
      before PCI, and catheterization or PCI not performed. Outside-referral STEMI, in
      patient STEMI, and failed thrombolysis patients were excluded. Data was obtained
      from medical records. Log transform of door-to-balloon (DTB) times was performed.
      RESULTS: Forty-seven events satisfied inclusion and exclusion criteria with 32
      occurring after RAPiD (post-RAPiD). Fifteen events occurred during on-hours (8 am
      to 7 pm on weekdays). Mean untransformed DTB times pre- and post-RAPiD were 162
      +/- 137 (standard deviation) minutes and 112 +/- 41 minutes. The main effects
      analysis of variance model showed a significant reduction in post-RAPiD DTB time
      (P = 0.03) with a mean reduction of 26% during off-hours and 20% during on-hours.
      The post-RAPiD estimate of mean DTB time, derived from the antilog of the log
      transform, was 96.7 minutes (95% confidence interval, 83.7-111.7). CONCLUSIONS:
      The institution of RAPiD in a hospital with a preexisting chest pain algorithm
      significantly decreases DTB times so as to satisfy current ACC/AHA guidelines.

PMID- 18340158
TI  - A triage algorithm for the rapid clinical assessment and management of emergency
      department patients presenting with chest pain.
AB  - This article describes an algorithm for the rapid clinical assessment and
      evidence-based managemant of patients presenting to the Emergency Department (ED)
      with chest pain. While broadly applicable, it is specifically designed for use in
      an ED-based chest pain unit, and incorporates time-sensitive pathways for
      patients with acute coronary syndromes as well as observation protocols for
      patients in which the etiology of chest pain is less clear.

PMID- 18340159
TI  - Improving care in patients with acute coronary syndromes: the Erlanger quality
      improvement initiative.
AB  - Quality improvement (QI) in emergency department (ED) patients with acute
      coronary syndromes (ACS) is a complex and dynamic phenomenon. ED physicians are
      faced with the challenge of multitasking a variety of patient complaints. This
      chaotic environment frequently hampers the ED physician's ability to properly
      evaluate and treat chest pain patients. Just as an airplane pilot would never
      take off without performing the comprehensive preflight operational checklist,
      the ED physician should have a standardized protocol for the evaluation and
      treatment of chest pain patients. In this report, we describe Erlanger Medical
      Center's 10-year QI initiative in developing a successful chest pain protocol for
      the rapid evaluation and treatment of patients with suspected ACS. Our initiative
      resulted from a collaborative effort among emergency physicians, cardiologists,
      nuclear radiologists, nursing staff, and administration. The systematic step-wise
      approach we utilized at our institution consisted of identification of the
      problem, development of standardized protocols, hospital-based QI initiatives,
      and continuation of QI efforts through national initiatives. Through this
      "building of bridges" among physicians, nursing, and administration, we hope that
      other institutions will modify our protocols to assist them in the development of
      their own successful QI program for improving the evaluation, treatment, and
      disposition of patients with suspected ACS.

PMID- 18340160
TI  - Understanding deep vein thrombosis.

PMID- 18340161
TI  - Dyslipidemia: the role of the hospitalist in guideline adherence and in-hospital
      initiation of therapy.

PMID- 18340162
TI  - Type 2 diabetes and the metabolic syndrome: National Cholesterol Education
      Program guidelines and supporting evidence.

PMID- 18340163
TI  - In-hospital initiation of lipid-lowering therapy.

PMID- 18340164
TI  - In-hospital initiation of lipid-lowering therapy: the role of the hospitalist.

PMID- 18340166
TI  - Dyslipidemia: raising the profile while lowering the levels.

PMID- 18340167
TI  - The hospitalist model of care: a positive influence on efficiency, quality of
      care, and outcomes.

PMID- 18340168
TI  - National Cholesterol Education Program guidelines and supporting evidence.

PMID- 18340169
TI  - A clinical and biochemical critical pathway for the evaluation of patients with
      suspected acute congestive heart failure: The ProBNP Investigation of Dyspnea in
      the Emergency Department (PRIDE) algorithm.
AB  - Dyspnea is a primary clinical manifestation of acute congestive heart failure
      (CHF) among patients presenting to the emergency department (ED). Unfortunately,
      other critical illnesses, including acute coronary syndromes, pulmonary embolism,
      chronic obstructive pulmonary disease, and pneumonia, may present with clinical
      symptoms and signs similar to acute CHF. N-terminal pro-brain natriuretic peptide
      (NT-proBNP) has proven to be a powerful tool in the diagnostic assessment of
      dyspnea as a result of its ability to confirm or exclude the presence of acute
      CHF. However, many of the disorders that mimic acute CHF may result in elevated
      NT-proBNP levels as well. Results from the ProBNP Investigation of Dyspnea in the
      Emergency Department (PRIDE) study recently demonstrated that a strategy
      integrating NT-proBNP testing into routine clinical assessment demonstrated a
      better diagnostic yield than each strategy used in isolation. We present a
      diagnostic algorithm integrating NT-proBNP testing with clinical assessment for
      use in routine clinical practice.

PMID- 18340170
TI  - Detection and management of aspirin resistance.

PMID- 18340171
TI  - Sedentary lifestyles, physical activity, and cardiovascular disease: from
      research to practice.
AB  - More than 60% of the world's population is not physically active at levels that
      promote health. In concert with other behavioral risk factors for cardiovascular
      disease (CVD), sedentary lifestyles exact a heavy medical and economic toll on
      individuals and societies. Physical activity lowers all-cause mortality, reduces
      several risk factors for cardiovascular disease, and is a category 2 intervention
      that can halve cardiovascular disease risk. The benefits extend across a wide
      spectrum of structured as well as lifestyle physical activity levels. Models and
      programs aimed at translating physical activity's promise in cardiovascular
      prevention have been assessed, but results have been generally disappointing. A
      pragmatic strategy based on the "stages of change" or transtheoretical model can
      be effective. It incorporates self efficacy and individual initiatives, both
      crucial ingredients necessary to surmount the inevitable hurdles on the path
      towards physically active lifestyles.

PMID- 18340172
TI  - Heart failure: an epidemic of the 21st century.
AB  - Heart failure is the leading cause of hospital admission in patients over the age
      of 65 in the United States and one of the leading causes of morbidity, mortality,
      and resource utilization in this country. This diagnosis carries an ominous
      prognosis worse than most cancers, and the financial burden exceeds 25 billion
      dollars a year. With the aid of a plethora of drugs, devices, and complementary
      therapies, heart failure management and outcomes have improved. However, as the
      country ages and more people survive their myocardial infarctions, as well as
      develop hypertension and diabetes, the incidence of heart failure continues to
      escalate. Heart failure has become such a broad epidemic that the American
      College of Cardiology, in collaboration with the American Heart Association, has
      developed new guidelines to prevent the development of systolic heart failure,
      thus changing the emphasis from clinical assessment to detection, intervention,
      and prevention. Hypertension and diabetes mellitus, in particular, are targeted
      as major risk factors for heart failure. These guidelines consist of 4 stages and
      provide objective categorization and evidence-based treatment recommendations
      from the literature for each of the stages. Inroads were made in the fight
      against heart attacks by the formation of care teams. Similarly, care teams for
      early identification of patients at risk, development of algorithms and critical
      pathways, and practicing evidence-based medicine are all within our capabilities
      for the battle against heart failure. Toward this end, the National Coalition for
      the Management of Left Ventricular Dysfunction has been formed and invites you to
      join in this comprehensive project to impact on the course of the heart failure
      epidemic at www.nclvd.org.

PMID- 18340173
TI  - PIES method of critique.
AB  - Critical evaluation of clinical trials is essential prior to applying results
      into clinical practice. We have created the acronym, PIES (Population,
      Intervention, Endpoints, and Statistics) that encapsulates the four basic aspects
      of a trial. The PIES method creates a systematic approach to critically
      evaluating a trial, allowing practitioners to formulate opinions as to the
      applicability to clinical practice.

PMID- 18340174
TI  - Postresuscitation myocardial stunning and its outcome: new approaches.
AB  - What is the successful cardiopulmonary resuscitation? It is the few minutes
      postcardiopulmonary arrest that can answer. Twenty to 40 percent of patients who
      sustained cardiac arrest are initially resuscitated, but only 10% survive to
      hospital discharge, and more than 60% of victims succumb within 24 hours. This
      high fatality rate in the early hours and days after successful resuscitation is
      mainly related to the acute, intense, and reversible form of postresuscitation
      myocardial dysfunction (stunning) together with the ventricular tachyarrhythmia.
      It is a reversible process, provided that we are aware of the pertinent
      pathophysiology and then intervene accordingly. Herein I reviewed most of the
      published relevant articles concerning the causes, underlying mechanism, and the
      updated trials for management of postresuscitation myocardial stunning. I do
      agree that not only the restoration of the circulation but also long-term outcome
      should be the aim of resuscitation, and I readdress the role of epinephrine,
      dobutamine, biphasic defibrillator, with the new promising agent (ie, potassium
      channel opener), Delta-opioid receptor agonist, unloading intracellular calcium,
      antioxidants, and therapeutic hypothermia to halt this period of stunning. This
      will improve the outcome of the resuscitation efforts.

PMID- 18340175
TI  - The use of vasodilators in the treatment of acute decompensated heart failure:
      novel versus conventional therapy.
AB  - The majority of patients who present with acute decompensated heart failure
      require the addition of vasodilators to adequately reduce filling pressures and
      improve symptoms. Conventional therapies such as nitroglycerin and nitroprusside,
      although relatively effective, are difficult to use. Nesiritide, a natriuretic
      peptide and neurohormonal antagonist with potent vasodilator properties, may be a
      reasonable alternative. It offers several benefits in safety and convenience over
      conventional vasodilators, making it particularly suitable for both emergency
      department and inpatient use.

PMID- 18340177
TI  - Critical Pathways in Cardiology, the official journal for the Society of Chest
      Pain Centers.

PMID- 18340176
TI  - Electron beam computed tomography for assessment of patients presenting to the
      emergency department with chest pain.
AB  - Electron beam computed tomography (EBCT) is a unique, noninvasive radiologic
      method capable of high-resolution imaging that is being increasingly used for
      evaluation of the cardiovascular system. Among its multiple applications,
      coronary artery calcium (CAC) imaging has attracted considerable attention
      because of the potential of this technique for early detection of coronary artery
      disease (CAD), the leading cause of mortality in our society. Although
      measurement of CAC has been primarily performed in the outpatient setting in both
      symptomatic and asymptomatic subjects, several studies have assessed the utility
      of the method to identify CAD in patients presenting to the emergency department
      with chest pain suggestive of myocardial ischemia but without objective evidence
      of the latter. This group comprises a majority of those presenting to the
      emergency department with chest pain, and their safe, accurate and cost-effective
      evaluation has been a continuing challenge.

PMID- 18340178
TI  - Positive impact of an interdisciplinary chest pain initiative on traditionally
      underserved populations.
AB  - BACKGROUND: We assessed the clinical impact of an interdisciplinary, cardiac
      nurse practitioner-facilitated chest pain (CP) initiative that stresses an early
      invasive approach for patients with CP with acute coronary syndromes in
      traditionally underserved patient populations, including females, blacks,
      Hispanics, and patients older than 60 years. METHODS: Two groups of patients were
      identified: Pre-CP initiative (December 1999-February 2000) and post-CP
      initiative (December 2000-February 2001). RESULTS: Analysis of 714 patients
      revealed significantly more cardiac diagnoses post-CP initiative (61% pre-CP
      initiative vs. 73% post-CP initiative, P = 0.002), including in patients with
      myocardial infarction (MI) who were older than 60 years, females, and Hispanics.
      There was a significant increase in rates of cardiac catheterizations within 1
      week of admission (10.5% vs. 20.4%, P <0.001), including in Hispanics. For rates
      of coronary artery stenting and/or bypass grafting (CABG), there was also a
      significant increase post-CP initiative (2.5% vs. 10.1%, P = 0.0005), as well as
      for Hispanics. Length of stay was significantly reduced for patients older than
      60 years (8.3 vs. 5.8 days, P = 0.002). CONCLUSION: Establishment of an
      interdisciplinary, cardiac nurse practitioner-facilitated CP initiative is
      associated with improvement in several clinical processes and outcomes: increased
      cardiac disease diagnosis in females, Hispanics, and patients older than 60
      years; increased rates of cardiac catheterizations in Hispanic patients,
      increased rates of coronary artery stenting and/or CABG, particularly in Hispanic
      patients; and decreased length of stay in patients older than 60 years. These
      data support a targeted interdisciplinary CP initiative as a strategy to
      systematically enhance access to cardiovascular diagnosis in underserved patient
      populations.

PMID- 18340179
TI  - B-type natriuretic peptide in heart failure: diagnostic, prognostic, and
      therapeutic use.
AB  - Chronic heart failure affects nearly 5 million people living in the United
      States, and the majority of economic burden is the result of hospitalizations for
      acute decompensated congestive heart failure. Patient history and symptom
      assessment, physical examination, and chest radiography remain the cornerstones
      of diagnosis and prognostic assessment. Evaluation of endogenous B-type
      natriuretic peptide (BNP) has emerged as a useful addition to standard methods
      for diagnosis and risk stratification of suspected congestive heart failure, and
      final diagnosis requires integration of BNP assays with traditional methods. BNP
      levels >500 pg/mL are more likely to be comfirmative of a primary diagnosis of
      heart failure and are also important predictors for long-term adverse prognosis;
      >100 pg/mL but <500 pg/mL suggests a reasonable likelihood for the diagnosis of
      heart failure but does require thoughtful exclusion of other potential
      confounders such as pulmonary disease resulting in right heart failure; and <100
      indicates that heart failure is very unlikely. Positive physiological effects of
      BNP, including improvements in hemodynamics, suppression of neurohormonal
      activity, preservation of renal function, diuresis and natriuresis, and balanced
      arterial and venous dilatation have suggested that this peptide also may have
      therapeutic use in congestive heart failure. In clinical trials, treatment of
      patients with acute decompensated congestive heart failure with nesiritide, a
      recombinant form of human BNP, was shown to significantly reduce pulmonary
      capillary wedge pressure versus placebo plus standard care, as well as provide a
      significant improvement in dyspnea versus placebo. Diagnostic, prognostic, and
      therapeutic applications of BNP can be integrated easily with standard methods to
      provide physicians with a useful evaluation and treatment algorithm that may
      result in faster identification of patients likely to benefit from early therapy,
      including nesiritide, thereby leading to the potential for more favorable patient
      outcomes.

PMID- 18340180
TI  - Use of statistical process control to support improved care for patients with
      acute myocardial infarction eligible for thrombolytic treatment: experience from
      2 hospitals in England during 2002-2003.
AB  - Efforts to reduce mortality from acute myocardial infarction (MI) through
      expediting thrombolytic and other reperfusion treatments have included the
      publication of clinical guidelines and standards of care for "door-to-needle"
      time in many countries. Across England, the National Service Framework, a
      national program of reform of cardiac care in the National Health Service, has
      resulted in, inter alia, significant reductions in treatment delay for
      thrombolysis-eligible patients. One component of the improvement program has been
      the use of service improvement methodologies, including statistical process
      control. We describe the early experience of 2 general hospitals in improving
      care of thrombolysis-eligible MI patients.

PMID- 18340181
TI  - How to join a clinical trial.

PMID- 18340182
TI  - Predictive instruments, critical care pathways, algorithms, and protocols in the
      rapid evaluation of chest pain.

PMID- 18340183
TI  - Pathway for the management of acute heart failure.
AB  - Acute heart failure poses a major healthcare problem. Recent guidelines for heart
      failure address management of outpatient chronic heart failure but do not address
      inpatient management. We present a unique, simple, yet comprehensive pathway that
      focuses on the differential diagnosis of new-onset heart failure and acute
      decompensation of chronic heart failure. An algorithm is presented for the
      optimal management of the patient with chronic heart failure who presents to the
      emergency room with acute symptomatic decompensation. The treatment algorithm
      provides recommendations for daily management and adjustments of therapy, which
      is primarily focused on a safe and rapid diuresis to the point of discharge from
      the acute care setting.

PMID- 18340184
TI  - Time to benefit: an emerging concept for assessing the efficacy of statin therapy
      in cardiovascular disease.

PMID- 18340185
TI  - What is the optimal timing of clopidogrel in acute coronary syndromes?

PMID- 18340186
TI  - A cooperative care model: cardiologists and hospitalists reduce length of stay in
      a chest pain observation unit.
AB  - Chest pain observation units are increasingly used to evaluate patients at low
      risk for cardiovascular events and are commonly staffed by cardiologists. The
      role of hospitalists in this setting has not been described. We assessed
      emergency department (ED) length of stay before and after adding hospitalists to
      the care team among 493 patients. Prior to intervention, median ED length of stay
      was 19.3 hours, which decreased to 11.0 hours with the addition of hospitalists
      (43% decrease, P <0.0001). No significant difference in 30-day cardiac event rate
      was observed (5% versus 6%, P = 0.68).

PMID- 18340187
TI  - Translation of critical pathways for acute coronary syndrome and for acute heart
      failure into admission forms and discharge planning.
AB  - We have recently developed and published 2 care pathways: 1 for the management of
      acute coronary syndrome and the other for acute heart failure. Our pathways are
      designed to optimize care for patients using clinical evidence models and to
      teach physicians in training consensus evaluation and management strategies. To
      implement our pathways to improve our patient care, we have developed unique
      admission and discharge forms derived from these pathways. These forms serve as
      reminders of key points of the pathways, as data collection devices, and most
      importantly as a health care agreement on discharge between patients and their
      healthcare providers.

PMID- 18340188
TI  - Tools for acute coronary syndromes from Northern California Kaiser Permanente.

PMID- 18340189
TI  - Unfortunate impact of age on the management and outcomes of unstable angina and
      non-ST elevation myocardial infarction (The GUARANTEE Registry).
AB  - Few data are available from the registries on the impact of age and gender on
      treatment and outcomes of patients admitted for unstable angina and non-ST
      elevation myocardial infarction (UA/NSTEMI). We examined the clinical
      characteristics, differences in management and outcomes, associated with age in
      2948 consecutive patients with UA/NSTEMI. Prospectively collected data from the
      Global Unstable Angina Registry and Treatment Evaluation (GUARANTEE) registry
      were analyzed, comparing patients older than 75 years of age and those 75 years
      and younger. Patients presenting at a younger age, both men and women, were more
      likely to have a family history of coronary artery disease, to be current
      smokers, and to have hypercholesterolemia (P < 0.001). Older patients more
      commonly had a prior history of stroke, angina, myocardial infarction (MI), and
      congestive heart failure (P < 0.05), and had more diffuse disease on angiography
      (P < 0.001). Although older women more often "ruled-in" for MI on admission, they
      were less likely to be cared for by a cardiologist (P < 0.05). A gradient in the
      use of cardiac catheterization was seen, with greatest use in younger men, 54.2%
      versus 47.4% for younger women, 43.1% for older men, and the lowest use in older
      women, 34.5% (P < 0.01). An opposite gradient of in-hospital mortality was seen,
      with 0.7%, 0.7%, 0.9%, and 3.2% across the 4 groups, respectively, with older
      women having worse outcomes (P = 0.008). Unfortunately, a "reverse targeting" of
      procedures to patient risk was seen among elderly, even when stratified by
      gender, with older patients being higher risk, but less likely to receive
      appropriate procedures. To improve the outcomes of elderly men and women with
      UA/NSTEMI, they should be managed more aggressively.

PMID- 18340190
TI  - Left main coronary angioplasty in surgical and nonsurgical candidates: putative
      role for a preconditioned expert culture on clinical outcome.
AB  - The impact of patient- and operator-related clinical variables of success and
      evaluation of subsequent midterm effects of percutaneous treatment of left main
      coronary stenosis were assessed at a tertiary-referral high-volume angioplasty
      center in a retrospective observational study. A total of 118 consecutive
      surgical and nonsurgical patients with protected and unprotected left main (LM)
      lesions were treated by operators within a preconditioned expert culture. There
      were 57 protected and 61 unprotected patients, including 13 patients with an
      acute myocardial infarction (AMI). Mean age was 67 years (range 33-90). The
      length of the stenotic segment was 4.8 +/- 2.3 mm, mean lumen diameter was 1.1 +/
      0.6 mm, and percentage diameter stenosis was 63.6 +/- 14.6%. There were 7 (5.9%)
      in-hospital cardiac deaths that presented with AMI and cardiogenic shock. All 7
      patients presented with unprotected LM lesions. Average follow-up was 8 months
      (range 1-36 months). Major adverse cardiac events (MACE) during follow-up
      comprised 8 (6.8%) cardiac deaths, 3 (2.5%) myocardial infarctions, 8 (6.8%)
      subjects with coronary bypass surgery, and 16 (13.6%) repeated angioplasties. The
      total event rate (MACE, n = 43) at the end of the follow-up period was 36.4%.
      There were more MACE in the unprotected group than in the protected group (41%
      vs. 31.6%, P<0.05). This study supports prior data on LM angioplasty. LM stenting
      in AMI showed less favorable in-hospital and late outcome.

PMID- 18340191
TI  - Nonemergent percutaneous coronary intervention with off-site surgery backup: an
      emerging new path to access.
AB  - Nonemergent primary coronary intervention (PCI) at hospitals with off-site
      cardiac surgery backup is currently given a "Class III" indication by the
      American College of Cardiology/American Heart Association (ACC/AHA) PCI
      Guidelines on the basis of "consensus opinion of experts," not on trials or
      studies (Level of Evidence C). Yet the evidence is mounting, both in the US and
      abroad, that urgent and elective PCI can be performed safely and effectively at
      qualified nonsurgical hospitals in controlled circumstances. As the need for PCI
      grows, especially in the large population with high-risk acute coronary syndromes
      (ACS), the lack of local access to and underutilization of timely PCI can
      demonstrably result in inferior outcomes. The multiple clinical, performance, and
      economic advantages of the broader availability of PCI are discussed extensively
      in this paper. Removing the requirement for on-site cardiac surgery from
      nonemergent PCI can also increase procedural volumes at the growing numbers of
      primary angioplasty programs at hospitals with off-site backup, while also
      reducing the pressure to build new low-volume cardiac surgery programs merely to
      support PCI programs. The many US hospitals that are already participating in
      this growing movement to provide PCI with off-site backup are encouraged to
      enroll in the ACC National Cardiovascular Data Registry to assure that this
      strategy is fairly assessed and monitored on a national level. We anticipate that
      state regulations and national guidelines will continue to evolve and keep pace
      with this growing movement and with the already-evolving guidelines from abroad.

PMID- 18340192
TI  - Brigham and Women's Hospital admission order set for unstable angina/non-ST
      elevation myocardial infarction.

PMID- 18340193
TI  - Implementation of critical pathways in the "real world".

PMID- 18340194
TI  - A cardiac discharge contract.

PMID- 18340195
TI  - Lack of utility of telemetry monitoring during transport to inpatient beds for
      identification of dysrhythmias for emergency department patients with potential
      and known acute coronary syndromes.
AB  - Patients admitted with acute and potential acute coronary syndromes (ACS)
      frequently required accompaniment by a registered nurse from the emergency
      department (ED) to inpatient telemetry beds. We tested the hypothesis that
      telemetry transport monitoring for patients with acute and potential ACS is of
      limited utility. We conducted a prospective cohort study of patients who were
      admitted from the ED with acute and potential ACS. Endpoints were life
      threatening ventricular dysrhythmias requiring intervention and duration of
      transport time. The setting was an urban tertiary-care emergency department with
      55,000 annual visits, and the subjects were adult patients admitted from the ED
      to inpatient beds (intensive care unit or floor telemetry) with ACS and potential
      ("rule-out") ACS. Main outcome measures were the development of a life
      threatening ventricular dysrhythmias during transport, any intervention by the
      transporting nurse, and the total transport time. Of 315 total admissions
      involving 310 patients, there were no life threatening ventricular dysrhythmias
      and interventions during transport [0%; 95% confidence interval 0-0.95%]. The
      total nurse time out of the ED spent transporting was 13.6 minutes (SD 5.2, range
      4-40). The routine use of nurses accompanying patients admitted with acute and
      potential acute coronary syndromes is of limited utility. Patient transportation
      without nurses may help alleviate ED overcrowding by saving almost 15 minutes of
      nursing time currently being used for transport without measurable benefit.

PMID- 18340196
TI  - The rate control, anticoagulation therapy, and electrophysiology/antiarrhythmic
      medication pathway for the management of atrial fibrillation and atrial flutter.
AB  - Atrial fibrillation is the most common cardiac rhythm disturbance encountered in
      clinical practice. Recent guidelines for the management of atrial fibrillation
      are complex and do not include the management of atrial flutter.To bridge the gap
      between currently available guidelines and patient management, we have developed
      a unique, simple, yet comprehensive pathway for the management of atrial
      fibrillation and atrial flutter. The pathway has been designed with the acronym
      RACE (rate control, anticoagulation therapy, and electrophysiology/antiarrhythmic
      medication) to reflect the 3 main components in patient management.This model is
      designed to mandate and then markedly improve adherence to the published American
      College of Cardiology, the American Heart Association and the European Society of
      Cardiology guidelines.

PMID- 18340198
TI  - View from the United Kingdom: chest pain center progress.

PMID- 18340197
TI  - Off-site percutaneous coronary intervention reduces hospital length of stay in
      vulnerable patients with acute myocardial infarction.
AB  - Primary percutaneious coronary intervention (PCI) is rapidly becoming the
      preferred therapy for acute ST-segment elevation myocardial infarction (AMI)
      because of a lower mortality rate and decreased hospital length of stay (LOS)
      compared with thrombolysis. However, generalizability of these findings beyond
      randomized trials involving specialized centers has not been well described. Many
      urban county hospitals care for disadvantaged patients and lack on-site PCI
      capabilities. Moreover, treatment delays and worse clinical outcomes have been
      demonstrated in this population. We sought to determine whether a shift from
      uniform on-site thrombolysis to off-site PCI for disadvantaged AMI patients
      reduces hospital LOS. We retrospectively reviewed 91 AMI patients presenting to
      an inner-city hospital without PCI capabilities, comparing 47 consecutive
      patients treated with off-site PCI with 44 historical controls who received
      thrombolysis. The primary end point was hospital LOS. Multivariable regression
      was used to adjust for baseline differences between the groups. Unadjusted median
      LOS was lower in the PCI group than the thrombolytic group (4 versus 6 days, P =
      0.004). These differences remained after adjusting for variation in baseline
      sociodemographic and clinical characteristics including the presence of
      cardiogenic shock. Fifteen patients (34%) in the thrombolytic group required
      urgent catheterization during index hospitalization versus none in the PCI group
      (P < 0.001). No differences in death or nonfatal reinfarction were noted 6 months
      after index event. This study supports the usefulness of primary PCI beyond
      highly selected populations in randomized controlled trials. Specifically, PCI
      significantly decreases hospital LOS among vulnerable AMI patients.

PMID- 18340199
TI  - Emerging diagnostics: impedance cardiography in the assessment and management of
      acute heart failure.

PMID- 18340200
TI  - Utility of brain natriuritic peptide as a diagnostic tool for congestive heart
      failure in the elderly.
AB  - We studied the performance characteristics of B-type natriuretic peptide (BNP) as
      a diagnostic test for congestive heart failure in the elderly dyspneic
      population. In a retrospective chart review study, dyspneic patients who had a
      BNP level drawn were included. To diagnose congestive heart failure (CHF), the
      Framingham Criteria were used. To diagnose pneumonia or a lower respiratory tract
      infection, the consensus development conference Criteria for Pneumonia/Lower
      Respiratory Tract Infection were used. Based on the criteria satisfied, the
      patients were categorized into one of 4 groups: group 1, pneumonia/lower
      respiratory tract infection; group 2, CHF; group 3, both; group 4, neither.
      Sensitivity, specificity, and positive and negative likelihood ratios were
      calculated for various BNP reference limits from 100 pg/ml upwards in increments
      of 100. A total of 70 patients (mean age 76.5) presenting with dyspnea were
      included in the study. Forty-six were females. The mean (+/-SD) BNP level for
      group 1 (n = 13) was 273 (+/-360) pg/ml, for group 2 (n = 30) it was 1394 (+/
      934) pg/ml, for group 3 (n = 17) it was 1138 (+/-842) pg/ml, and for group 4 (n =
      10) it was 403 (+/-362) pg/ml. Forty-seven patients (groups 2 and 3) met the
      Framingham criteria (CHF+). The other 23 (groups 1 and 4) did not (CHF-). The
      sensitivity and specificity of BNP for CHF at a cutoff of 100 pg/ml was 96% and
      26%, respectively. The sensitivity (87%) and specificity (74%) were optimal at a
      cutoff of 400 pg/ml. Our study indicates that the specificity of a BNP level of >
      or = 100 pg/ml for diagnosing CHF in the elderly is poor. Our data suggest an
      optimal BNP value of > or = 400 pg/ml. Elderly patients frequently have multiple
      etiologies contributing to dyspnea. In our study, one-fourth of the patients
      satisfied the criteria for a dual diagnosis of CHF and pneumonia.

PMID- 18340201
TI  - Acute coronary syndrome critical pathway: chest PAIN caremap: a qualitative
      research study--provider-level intervention.
AB  - Recently published data on healthcare performance continue to show a substantial
      gap between evidence-based guidelines and management of patients in real-world
      settings. This article describes an operational model that will be used to test
      whether a critical pathway applied in a secondary care-level institution may
      improve the process of care related to acute coronary syndromes (ACS). We have
      developed the pathway for management of all patients who present to our emergency
      department with a chief complaint of acute chest pain. Based on individual
      immediate ischemic event risk, patients are categorized according to a
      prespecified algorithm under the acronym of "PAIN" (P-Priority risk, A-Advanced
      risk, I-Intermediate risk, and N-Negative/low risk) as prespecified in an
      algorithm. Along with the algorithm come 2 detailed order sets, 1 for ST
      elevation ACS and another for non ST-elevation ACS. The pathway, together with
      the 2 order sets, are color-coded with the "PAIN" acronym (P-red, A-yellow, I
      yellow, N-green) that will guide patient management according to his or her risk
      stratification. These colors, similar to the road traffic light code, have been
      chosen as an easy reference for the provider about the sequential risk level of
      patients with ACS. This experimental model intends, with its unique structured
      approach, to increase awareness and improve adherence to the published American
      Heart Association/American College of Cardiology guidelines for the management of
      ACS.

PMID- 18340202
TI  - Integrating clinical practice guidelines into the routine of everyday practice.
AB  - For years, the American College of Cardiology and the American Heart Association,
      along with other professional organizations, have produced clinical practice
      guidelines to improve the quality of cardiovascular care. Producing these
      comprehensive documents has required extraordinary effort, primarily from
      volunteer professionals. Quality improvement efforts based on these guidelines,
      however, have not fully engaged practicing physicians, as evidenced by studies of
      guideline adherence. The translation of the guidelines into routine practice
      remains a persistent challenge.Practitioners work in a complex and fast paced
      environment. In the routine of everyday practice, physicians, like all decision
      makers, use cognitive shortcuts to help make rapid decisions under conditions of
      uncertainty. How practicing physicians package information in their working
      memory and use shortcuts called "heuristics" has implications for how clinical
      practice guidelines can most directly influence practice. Current guidelines are
      written as comprehensive review documents, but are not formatted to allow easy
      incorporation into the heuristics of everyday practice. Improving the interface
      between guidelines and routine practice may result in more rapid and appropriate
      translation of scientific evidence into practice.We describe the routine of
      everyday practice as a repetitive cycle where new scientific evidence is
      incorporated into the heuristics that drive daily medical decisions. Examining
      this cycle suggests ways to communicate guideline information more effectively
      and to improve practice routines. Recognizing the intuitive approaches that
      practicing physicians use to make rapid decisions may yield opportunities for
      responsive professional organizations and reflective practicing physicians to
      improve the quality of care.

PMID- 18340203
TI  - Are statins being underdosed in clinical practice? Data from TACTICS-TIMI 18.
AB  - BACKGROUND: Although clinical trials in the 1990s have found significant
      reductions in cardiovascular events with fixed doses of statins, specifically 40
      mg of simvastatin or pravastatin, in clinical practice, treatment is usually
      initiated at lower doses. It is not clear, however, if the doses are then
      titrated upward after the initial dosing. METHODS: We examined the dosing for
      patients receiving statins at the time of entry and at 6 months follow-up in the
      Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or
      Conservative Strategy-Thrombolysis In Myocardial Infarction (TACTICS-TIMI) 18
      trial, and their relationship to the measured low-density lipoprotein cholesterol
      (LDL-C) on admission. RESULTS: In the TACTICS-TIMI 18 trial, 727 of 2220 (33%)
      patients with unstable angina and non-ST elevation MI were on statins at study
      entry, of whom 371 had both LDL-C measurements and statin dose recorded on
      admission: 132 (36%) received atorvastatin, 126 (34%) simvastatin, 58 (16%)
      pravastatin, and the remainder lovastatin, fluvastatin, or cerivastatin. Only 18%
      and 38% of patients were treated with the 40-mg dose of simvastatin or
      pravastatin, respectively. Only 3 patients on atorvastatin were treated with 80
      mg. At entry, 46% of these patients had LDL-C < or =100 mg/dL (and even among all
      patients with either prior MI, CABG, PTCA, or diabetes, only 33% had LDL-C < or
      =100 mg/dL, increasing modestly to 48% for those also on a statin). At 6 months
      after the UA/NSTEMI event, although more patients (1113, 50%) were on statins,
      the doses used were not higher then those used at baseline. CONCLUSION: We
      observed that the doses of statins in clinical practice were usually lower than
      those used in the clinical efficacy trials. Furthermore, LDL-C of < or =100 mg/dL
      was achieved in fewer then 50% of acute coronary syndrome patients receiving
      statins at time of presentation. These data suggest that, in addition to
      previously documented underutilization of statins in clinical practice, there is
      also underdosing of this important class of drugs.

PMID- 18340204
TI  - Treating to low-density lipoprotein goal: a tool for initiating and optimizing
      lipid-lowering therapy in patients with atherosclerosis or similar risk.
AB  - Compelling, consistent clinical trial evidence indicates that lipid-lowering
      therapy reduces the risk of recurrent cardiovascular events and improves survival
      in patients with coronary heart disease, cerebral vascular disease, peripheral
      vascular disease, and diabetes. Despite this evidence and the national clinical
      guidelines recommending lipid-lowering treatment and low-density lipoprotein
      (LDL) goal attainment in patients with clinically evident atherosclerotic
      vascular disease or similar risk, study after study has documented low treatment
      rates. Furthermore, a large proportion of high-risk patients have not achieved
      LDL goals, thereby creating a clinical practice and public health dilemma. This
      article features a tool to guide the initiation and optimization of LDL-lowering
      therapy and a program to improve long-term treatment rates, LDL goal attainment,
      and clinical outcomes.

PMID- 18340205
TI  - Future options for management of heart failure in an emergency department
      observation unit.
AB  - In the next year there will be over 1 million United States hospitalizations for
      acute decompensated heart failure (ADHF), with 80% admitted to the hospital
      through the emergency department. The short stay Observation Unit represents a
      new strategy for diagnosis and treatment of ADHF. This manuscript examines some
      of the promising options that may become available to the practitioner in the
      near future. These include 1) ultrafiltration, where excess fluid is removed by
      the application of a minimally invasive extracorporeal blood circuit; 2) digital
      sound wave analysis, which provides improved specificity for the diagnosis of
      ADHF; 3) and intermittent infusion therapy, where initial studies suggest
      infusion therapy with nesiritide may improve chronic outcomes. These applications
      may be uniquely appropriate for the observation unit environment. While not
      currently mainstream or standard of care in their current usage, these
      opportunities may represent foreseeable directions in the early diagnosis and
      treatment of ADHF. Future research will place these maneuvers into their
      appropriate diagnostic and therapeutic roles, which will hopefully provide
      benefit to our patients.

PMID- 18340206
TI  - Supervision and interpretation of exercise treadmill tests by physician
      assistants.

PMID- 18340207
TI  - Update to International Classification of Diseases, 9th Revision codes:
      distinguishes STEMI from NSTEMI.

PMID- 18340208
TI  - View from Argentina: chest pain centers progress.
AB  - The prevalence of acute coronary syndromes (ACS) throughout the world has been a
      stimulus for the development of chest pain centers beyond the United States,
      where the concept first emerged. The rationale for the development of chest pain
      centers in Argentina includes the abundance of ACS and the objective of
      optimizing healthcare delivery.

PMID- 18340209
TI  - Diagnosis and management of the metabolic syndrome: an American Heart
      Association/National Heart, Lung, and Blood Institute scientific statement:
      Executive Summary.

PMID- 18340210
TI  - The evaluation and management of cardiogenic shock.
AB  - Cardiogenic shock (CS) continues to be the leading cause of death in patients who
      present to the hospital with acute myocardial infarction (AMI). Mortality in
      patients with AMI complicated by CS remains extremely high, with 1-month
      mortality rates ranging from 40% to 60%. Although pump failure is the dominant
      etiologic feature of CS after AMI, the inflammatory system has been implicated in
      its pathogenesis. The dominant therapy for treatment of CS is early mechanical
      revascularization with either percutaneous coronary intervention or coronary
      artery bypass graft surgery. Supportive measures such as intravenous vasopressors
      or intra-aortic balloon counterpulsation can complement the benefit of definitive
      revascularization. Newer therapies are directed at mitigating the inflammatory
      response or supporting cardiovascular function until either patient recovery or
      until other destination therapy is available. The strategies in this critical
      pathway outline the general approach in treating CS after AMI at our institution.

PMID- 18340211
TI  - Clinical tools for cardiovascular risk assessment/prevention/management:
      APOLLOlipids.org.

PMID- 18340212
TI  - Translation of the RACE pathway for management of atrial fibrillation and atrial
      flutter into admission forms.

PMID- 18340213
TI  - They're watching you! Performance measurement, staffing, and facilities
      requirements.
AB  - The aim of this article is to convey the importance of attention to performance
      measures, staffing, and facilities requirements when planning a heart failure
      management program in a short-stay area. Written performance measures that
      reflect care excellence and act as standards of care will ensure consistency in
      care delivery and lead to improved patient outcomes. Staffing can be carried out
      in many ways (physician led-program, physician-advanced practice nurse-led
      program, nurse-mediated care program, or multidisciplinary providers of care);
      however, a clinical leader willing to champion the program should be sought to
      promote performance achievement, negotiate for facilities resources, and guide
      staff through education and example. Facilities requirements include tools (forms
      that embed evidence-based practice to augment standards of care such as care
      algorithms, admission and discharge forms, and patient education materials) and
      devices that aide in patient assessment, diagnosis, management, and education.
      Minimal device resources needed to meet performance measures are access to
      echocardiography and B-type natriuretic peptide serum testing.

PMID- 18340214
TI  - Case management for heart failure in the emergency department.
AB  - Heart failure affects approximately 5 million individuals in the United States
      and is the most common discharge diagnosis among the elderly. The number of
      individuals diagnosed with heart failure will continue to rise as the population
      of the United States ages. The natural course of the disease is characterized by
      periods of stability interrupted by periods of symptom exacerbation. These
      periods of exacerbation often require emergency intervention or hospitalization
      for management. Once an individual is hospitalized, they are at a greater risk
      for rehospitalization. The causes of rehospitalizations are multifactorial and
      many are preventable. Case managers are in a position to have a positive impact
      on the readmission rate. Interventions include adherence to medication
      guidelines, increasing patients' knowledge of self-care measures, assessing
      discharge readiness and needs, and increasing the frequency of symptom monitoring
      for early intervention. Case management begins in the emergency department and
      facilitates care throughout the patient's stay by fostering communication among
      all caregivers and the patient and family. Case managers also affect the quality
      of care patients receive by instituting processes that streamline care and ensure
      that quality care is provided to the patients. They also serve as mentors and
      resources for other members of the healthcare team. Most of the information about
      case management comes from inpatient and outpatient programs; however, the
      emergency department nurse can adapt these models to support their role. More
      research is needed as to what specific portions of the case manager's role are
      most appropriate for the emergency department.

PMID- 18340215
TI  - Comprehensive hospital care improvement strategies reduce time to treatment in ST
      elevation acute myocardial infarction.
AB  - BACKGROUND: Delay in treatment of patients with ST-elevation acute myocardial
      infarction (STEMI) has an adverse effect on patient outcomes. Limited data are
      available on the effectiveness of hospital care improvement strategies (HCIS) to
      reduce time to reperfusion by percutaneous coronary intervention (PCI). This
      study evaluated the combined effect of HCIS implementation to reduce door-to
      balloon time in patients with STEMI. METHODS: Retrospective chart review was done
      for 95 consecutive patients with STEMI who underwent PCI at Charleston Area
      Medical Center. Patients with non-STEMI and patients transferred from other
      medical centers were excluded. Door-to-balloon time was defined as time from
      emergency department arrival to first PCI balloon inflation. A program of 3 HCIS
      was implemented: 1) a fast-track catheterization laboratory protocol, 2) feedback
      to cardiologists on their treatment times, and 3) a weekday 24-hour inhouse
      catheterization laboratory team. Patients were separated into groups before (n =
      46), during (n = 18), and after (n = 31) HCIS implementation. RESULTS: Mean age
      was 60.3 +/- 13 years and 74% were male. The majority (64%) arrived by ambulance;
      29% had a prehospital electrocardiogram done. Most patients presented during the
      day (68%) on weekdays (75%). Symptom onset-to-door time was 289 +/- 393 minutes.
      No significant differences were found between the groups for these variables.
      Door-to-PCI time in minutes was reduced in the group after versus the group
      before HCIS implementation (94.3 +/- 37 vs 133.5 +/- 53; P < 0.0001). CONCLUSION:
      Implementation of HCIS shortened door-to-PCI time for patients with STEMI by 39.2
      +/- 10 minutes. Thus, HCIS may be effective in improving patient outcomes.

PMID- 18340216
TI  - Increasing the speed and delivery of primary percutaneous coronary intervention
      in the community: should the ACC/AHA Guidelines be revisited?

PMID- 18340217
TI  - Comment on "Increasing the speed and delivery of primary percutaneous coronary
      intervention in the community: should the ACC/AHA Guidelines be revisited?".

PMID- 18340218
TI  - Acute coronary syndrome: the Time is Life Campaign at the Veterans Administration
      Medical Center San Diego.

PMID- 18340219
TI  - Missed diagnosis of the diagnosis codes: comparison of International
      Classification of Diseases, 9th Revision coding and ST- versus non-ST-elevation
      myocardial infarction diagnosis in the National Registry of Myocardial
      Infarction.
AB  - BACKGROUND: Although International Classification of Diseases, 9th Revision (ICD
      9) codes have been in use for decades to classify patients with acute myocardial
      infarction (AMI) in the United States, they did not allow characterization of
      patients with ST elevation MI (STEMI) versus non-ST elevation myocardial
      infarction (NSTEMI). METHODS: We evaluated all discharged patients with AMI
      participating in the National Registry of Myocardial Infarction 2, 3, and 4
      databases with coded ICD-9 information. Patients who were transferred out to a
      different institution were excluded. A comparison of the ICD-9 codes used for
      STEMI and NSTEMI patients, as determined by electrocardiography (ECG), was
      performed. A comparison of mortality for patients that were neither transferred
      in or out was also performed. RESULTS: Among 1.45 million patients, 521,332
      (36.1%) had STEMI and 923,757 (63.9%) had NSTEMI based on presenting ECG
      criteria. There were 10.9% of those with STEMI who were coded as 410.71
      (subendocardial MI). In contrast, 38.8% of NSTEMI patients had an ICD-9 code
      other than 410.71. Mortality across ICD-9 codes was similar between the STEMI and
      NSTEMI groups overall and within each ICD-9 subsection. CONCLUSION: Substantial
      overlap and inconsistency exists in ICD-9 codes for STEMI and NSTEMI patients,
      yet both ICD-9 code and STEMI predicted mortality. The new changes to ICD-9
      coding, implemented in October 2005 to segregate STEMI and NSTEMI, should allow
      better description of quality measures and outcomes of these 2 distinct types of
      MI patients.

PMID- 18340220
TI  - Assessing the need for functional diagnostic testing in low-risk women with chest
      pain.
AB  - OBJECTIVE: The objective of this study was to assess the need for functional
      diagnostic testing to identify coronary artery disease (CAD) in women presenting
      with chest pain and deemed at low risk in a chest pain evaluation unit (CPEU)
      setting. METHODS: Low-risk women evaluated in a CPEU were defined as having < or
      =1 intermediate determinant of CAD (hypertension, tobacco use, or
      hypercholesterolemia) or < or =2 minor determinants (age, obesity, sedentary
      lifestyle, or family history of CAD). Patients were followed for 30 days for the
      occurrence of CAD, defined as a positive stress imaging study, significant CAD on
      angiography, myocardial revascularization, myocardial infarction (MI), or cardiac
      death. RESULTS: Of 1355 consecutive women evaluated, 527 (39%) were classified as
      low risk. The rate of CAD in the low-risk group was 1.3% of which there were no
      coronary events. CONCLUSION: Women admitted to a CPEU and identified as low risk
      are at very low risk for CAD.

PMID- 18340221
TI  - Acute Coronary Syndromes Clinical Practice Guidelines.

PMID- 18340222
TI  - The clinical potential of a point-of-care assay to assess interindividual
      variability in platelet aggregation among patients taking clopidogrel.
AB  - Clopidogrel is an important component of medical therapy for patients with acute
      coronary syndromes and those receiving coronary artery stents. Despite use of
      clopidogrel, a significant number of patients experience recurrent adverse
      ischemic events. Interindividual variability of platelet aggregation in response
      to clopidogrel may be an explanation for some of these recurrent events, and
      small trials have linked "clopidogrel resistance" as measured by platelet
      function tests to adverse events. Additionally, the degree of clopidogrel-induced
      platelet inhibition appears to be a factor determining bleeding risk at coronary
      artery bypass grafting. A point-of-care device that could accurately and rapidly
      measure the degree of platelet inhibition among patients taking clopidogrel could
      be clinically valuable. Such a device would have the potential to allow
      therapeutic decision-making based on the degree of platelet inhibition,
      especially for patients undergoing percutaneous coronary intervention or coronary
      artery bypass grafting.

PMID- 18340223
TI  - Pathway for the management of hyperglycemia in critical care units.
AB  - Inhospital morbidity and mortality are increased in hyperglycemia. Normalization
      of blood glucose levels using intensive insulin infusion protocols improves
      clinical outcomes. Insulin infusion algorithms have been shown to be safe and
      effective; however, a major obstacle in their implementation is their complexity.
      We have developed a novel pathway for the management of hyperglycemia, which
      introduces the "wheel" concept for insulin dosing complemented by "catchup"
      insulin dosing. The "wheel" serves as a treatment guide. It is made up of 4
      concentric circles. The inner circle features blood glucose ranges and the 3
      outer circles correspond to increasing rates of insulin infusion. Simple
      guidelines are provided to facilitate conversion from insulin infusion to a
      subcutaneous insulin-delivery regimen in preparation for transfer from the
      critical care unit setting. Our protocols eliminate reliance on the familiar
      "sliding scale" insulin administration schemes with the introduction of "catchup"
      insulin dosing to supplement the basic regimen. This pathway is comprehensive yet
      simple and provides guidelines for treatment of hyperglycemia for all patients
      screened to a critical care unit or to a stepdown unit.

PMID- 18340224
TI  - Translation of hyperglycemia pathway into a critical care worksheet.

PMID- 18340225
TI  - Use of additional electrocardiograph leads in low-risk patients undergoing
      exercise treadmill testing.
AB  - BACKGROUND: Studies have shown that the addition of right precordial and left
      posterior leads to the standard 12-lead electrocardiogram (ECG) can significantly
      improve the sensitivity of exercise treadmill testing (ETT) for the diagnosis of
      myocardial ischemia. OBJECTIVE: The objective of this study was to determine the
      value of adding 2 rightsided (RV3, RV4) and 2 left posterior (V8, V9) auxiliary
      leads to enhance detection of myocardial ischemia in patients with chest pain
      identified as low risk. METHODS: The authors conducted a prospective study of all
      patients undergoing ETT as part of their management in a chest pain evaluation
      unit (CPEU) at a tertiary medical center from November 1999 to November 2001.
      Patients were considered low risk for acute coronary syndrome based on the
      clinical presentation to the CPEU, absence of ischemia on resting ECG, and
      negative initial cardiac markers. Diagnosis of coronary artery disease (CAD) was
      based on confirmatory testing, which included coronary angiography, myocardial
      stress scintigraphy, exercise echocardiography, or 30-day follow-up period.
      RESULTS: The study cohort comprised 705 patients who underwent 16-lead ETT. Of
      these, 70 (10%) had positive ETT and CAD was confirmed by further evaluation in
      26. ECG changes positive for ischemia were demonstrated on the standard 12-lead
      exercise ECG in 68 patients. An additional 2 patients had positive ECG
      alterations only in the 4 auxiliary leads on the 16-lead ECG. There was no
      significant difference in the sensitivity or positive predictive value between
      the 12- and 16-lead exercise ECG. CONCLUSION: Electrocardiographic changes in
      auxiliary leads did not change the diagnostic use of the ETT and therefore may
      provide only a minimal contribution to the assessment of the low-risk CPEU
      population.

PMID- 18340226
TI  - The Chest Pain Center movement and the need to develop a quasi-public health
      initiative for improving heart attack care in the United States.

PMID- 18340227
TI  - Prehospital fibrinolysis.
AB  - Reperfusion therapy for ST-elevation acute coronary syndromes aims at early and
      complete recanalization of the infarct-related artery to salvage myocardium and
      improve both early and late clinical outcomes. Prehospital diagnosis of ST
      elevation acute coronary syndrome can be made by electrocardiography with or
      without transtelephonic transmission, and subsequent fibrinolytic therapy can be
      instituted at home or in the ambulance. Prehospital fibrinolysis decreases time
      to treatment by approximately 1 hour compared with in-hospital therapy resulting
      in a significant 15% relative risk reduction in early mortality. This may compare
      well with primary angioplasty for ST-elevation acute coronary syndrome, although
      more studies are necessary.

PMID- 18340228
TI  - Thrombolysis for ST-elevation myocardial infarction in the emergency department.

PMID- 18340229
TI  - Regional transfer programs for primary percutaneous coronary intervention.

PMID- 18340230
TI  - Management of STEMI: assessment of reperfusion options.

PMID- 18340231
TI  - Prehospital electrocardiogram and early helicopter dispatch to expedite
      interfacility transfer for percutaneous coronary intervention.
AB  - Care provision and benchmarking for patients with ST-elevation myocardial
      infarction (STEMI) have focused on streamlining time between initial hospital
      presentation and opening of theinfarct-related artery. In a Boston-area regional
      system already characterized by expedited advanced life support (ALS) dispatch
      and paramedic performance of prehospital electrocardiogram (EKG), a critical
      pathway was designed that allows for helicopter dispatch based on ground ALS
      providers' STEMI diagnosis. The pathway dictates that as soon as ALS crews make
      the diagnosis of STEMI from their 12-lead EKG, they will contact Boston MedFlight
      (BMF) and a helicopter will be immediately dispatched to the participating
      community hospital (Lawrence General Hospital [LGH]). Based on historical and
      predicted time patterns, it is expected that BMF will arrive at LGH soon after
      the ALS ambulance delivers the patient to the LGH emergency department (ED). The
      patient will then undergo BMF transport from the ED into central Boston with
      direct transfer into an awaiting cardiac catheterization suite (ie, bypassing the
      receiving hospital ED). The pathway minimizes the delay between patient arrival
      at LGH and BMF arrival for transport to the catheterization laboratory. It is
      hoped that implementation of the critical pathway will allow the region's
      patients with STEMI to achieve coronary arterial patency within 90 minutes of LGH
      presentation. If the pathway proves effective, it can serve as a model for other
      regions and programs with similar clinical and logistic situations and advance
      the concept of "diagnosis-to-balloon" time.

PMID- 18340232
TI  - National impact of the troponin diagnostic standard on the prevalence and
      prognosis of acute myocardial infarction in older persons.
AB  - BACKGROUND: Consensus guidelines from the American College of Cardiology, the
      American Heart Association, and the European Society of Cardiology have made
      cardiac troponin central to the diagnosis of acute myocardial infarction (AMI).
      Although multiple studies have shown that the troponin diagnostic standard
      facilitates the identification of new AMI cases in the general population, and
      that elevations of troponin are associated with poor prognosis, questions remain
      regarding the impact of the troponin diagnostic standard on the prevalence and
      prognosis of AMI in older persons. METHODS: Nationwide samples of eligible
      Medicare beneficiaries aged > or =65 years who were hospitalized (n = 71,120)
      with a primary discharge diagnosis of AMI between April 1998 and March 1999
      (baseline cohort) or July 2000 and June 2001 (remeasurement cohort) were
      evaluated. The analysis was restricted to patients with clinically confirmed AMI
      who underwent testing for both CK-MB and troponin. RESULTS: The majority of these
      patients (71.0%) were both CK-MB- and troponin-positive, but 17.8% were diagnosed
      with AMI based solely on positive troponin levels. Combining the CK-MB or both
      groups as a reference and troponin as a design variable to fit Cox proportional
      hazards models, troponin-only-positive patients had an unadjusted risk ratio (RR)
      of 1.14 (95% confidence interval [CI], 1.07-1.22) for the 30-day mortality and RR
      of 1.09 (95% CI, 1.03-1.15) for the 3-year mortality. However, after adjusting
      for patient demographics, clinical characteristics, physician specialties, and
      hospitals characteristics, troponin-only-positive patients had similar risk for
      early- and long-term mortality as the other 2 groups; the risk-adjusted RR for 30
      day mortality was 0.96 (95% CI, 0.89-1.02) and for 3-year mortality was 0.95 (95%
      CI, 0.90-1.00). CONCLUSION: The widespread application of cardiac troponins
      results in a substantial increase in AMI diagnoses in older patients. Contrary to
      the prevailing wisdom that troponin-only-positive AMIs are smaller "infarctlets"
      and likely to have better prognosis, older persons with troponin-only AMIs are at
      similar risk for early and long-term mortality compared with those with CK-MB
      positive AMIs. Therefore, nationwide efforts should focus on the unique
      characteristics of this emerging patient population so as to improve quality of
      care provided to this high-risk cohort of patients with AMI.

PMID- 18340233
TI  - Early invasive strategy improves outcomes in patients with acute coronary
      syndrome with previous coronary artery bypass graft surgery: a report from
      TACTICS-TIMI 18.
AB  - BACKGROUND: Patients with previous coronary artery bypass graft surgery (CABG)
      have been classified as a high-risk subset of patients who experience non-ST
      elevation acute coronary syndrome (ACS). Recent studies suggest that an early
      invasive strategy is beneficial in moderate- and high-risk patients with non-ST
      elevation ACS. We hypothesized that an early invasive strategy is associated with
      improved outcomes in patients with non-ST elevation ACS with prior CABG. METHODS
      AND RESULTS: In the Treat Angina with Aggrastat and determine Cost of Therapy
      with an Invasive or Conservative Strategy-Thrombolysis in Myocardial Infarction
      18 trial (TACTICS-TIMI 18), 2220 patients with non-ST segment elevation ACS were
      randomized to an early invasive or conservative (selectively invasive) strategy.
      All patients were treated with aspirin, heparin, and tirofiban. Four hundred
      eighty-four (22%) of these patients had undergone CABG before enrollment. We
      analyzed whether patients with previous CABG had different 6-month outcomes and
      whether an early invasive strategy was associated with an improvement in long
      term outcomes. Prior CABG was associated with a higher risk of adverse outcomes
      by 6 months, including a higher rate of readmission for ACS (17.4% vs 11.0%, P <
      0.001) and a higher incidence of the composite end point of death, myocardial
      infarction, or rehospitalization for ACS (22.3% vs 16.4%, P = 0.002). There was a
      trend toward a higher incidence of myocardial infarction (7.1% vs 5.3%, P =
      0.051). An early invasive strategy was associated with a reduction in the
      composite of death or myocardial infarction (odds ratio [OR], 0.58; 95%
      confidence interval [CI], 0.31-1.0; P = 0.089) and a significant reduction in the
      incidence of myocardial infarction at 6 months (OR, 0.44; 95% CI, 0.21-0.93;
      P=0.032). CONCLUSIONS: Patients with non-ST segment elevation ACS who have had
      previous CABG are a high-risk subset. An early invasive strategy reduces risk of
      myocardial infarction in this high-risk group.

PMID- 18340234
TI  - The SELF pathway for the management of syncope.

PMID- 18340235
TI  - Overview of the American Heart Association "Get with the Guidelines" programs:
      coronary heart disease, stroke, and heart failure.

PMID- 18340236
TI  - The first SHAPE (Screening for Heart Attack Prevention and Education) guideline.
AB  - Atherosclerotic cardiovascular disease (A-CVD) is preventable. Major causal risk
      factors are known, and effective and safe treatments exist. However, A-CVD
      remains the leading cause of death and severe disability not only in affluent
      countries, but also globally. The burden of A-CVD is growing faster in poor and
      developing countries threatening their future economic development. Traditional
      methods for prevention of A-CVD have proven largely insufficient. Although many
      societal factors contribute to the epidemic of A-CVD (eg, smoking, obesity,
      diabetes, insufficient physical activity, and so on) and deserve renewed
      attention, early detection of the asymptomatic vulnerable patient who has
      significant subclinical atherosclerosis presents as a low hanging fruit in
      primary prevention of A-CVD. The Screening for Heart Attack Prevention and
      Education (SHAPE) Task Force, comprised of an international group of experts, has
      proposed the First SHAPE Guideline to address a major shortcoming in the existing
      guidelines in primary prevention of A-CVD. It is based on the observation that
      most heart attacks and strokes occur in people who are not classified as high
      risk by the traditional risk factor-based approach recommended in the United
      States (Framingham Risk Score) and Europe (SCORE). Unfortunately, these
      guidelines provide inadequate warning to asymptomatic individuals with
      subclinical atherosclerosis who are unaware of their high-risk status and are not
      aggressively treated by their physicians who follow the existing recommendations.
      Consequently, most of these asymptomatic individuals, who are vulnerable to a
      near-future heart attack, are not offered the benefit of existing prophylactic
      therapies. Unlike decades ago when screening for risk factors of A-CVD was the
      only available risk stratification method in primary prevention, today,
      noninvasive detection of atherosclerosis is feasible and widely available. It
      provides a direct and individualized method for risk assessment. A large body of
      evidence has been compiled in recent years showing the superior prognostic value
      of detecting atherosclerosis rather than risk factors of atherosclerosis. The
      First SHAPE Guideline calls for noninvasive screening of all asymptomatic men 45
      to 75 years old and asymptomatic women 55 to 75 years old (except those defined
      as very low risk) to detect and treat individuals with subclinical
      atherosclerosis. The intensity of treatment should correlate with the severity of
      the disease. Among existing tools for detection of subclinical atherosclerosis,
      the SHAPE Task Force has created the SHAPE Flow Chart based on the following 2
      noninvasive imaging techniques: coronary artery calcium scoring using computed
      tomography and carotid intima media thickness and plaque using B-mode
      ultrasonography.

PMID- 18340237
TI  - Contemporary scientific insights: role of biomarkers of inflammation in
      cardiovascular disease/atherosclerosis.

PMID- 18340238
TI  - Venous Thromboembolism Guidebook: fifth edition.

PMID- 18340239
TI  - Understanding prehospital delay behavior in acute myocardial infarction in women.
AB  - Studies demonstrate that acute myocardial infarction (AMI) mortality can be
      reduced if reperfusion therapy is initiated within 1 hour of AMI symptom onset.
      However, a considerable number of men and women arrive at the emergency
      department outside of the time frame for thrombolytic and angioplasty
      effectiveness. This is especially true for women who have been shown to delay
      longer than men due to their prehospital decision-making process utilized. With a
      mean total delay time greater than 4 hours, the time interval from symptom onset
      to transport activation to the hospital consumes the majority of the prehospital
      phase of emergency cardiac care. The health belief model, self-regulation model,
      theory of reasoned action, and theory of planned behavior have all been used to
      describe the prehospital decision-making process of both men and women with an
      AMI and the variables that impact that process. These models have identified the
      importance of symptom attribution to cardiac-related causes as a target variable
      for research and interventions related to care-seeking behavior.

PMID- 18340240
TI  - Summary of the methodology for the validation study for a termination of
      resuscitation clinical prediction rule.

PMID- 18340241
TI  - Exemestane: an alternative treatment option in early breast cancer. Foreward.

PMID- 18340242
TI  - Intergroup Exemestane Study mature analysis: overall survival data.
AB  - The findings of the Intergroup Exemestane Study (IES) challenge the standard
      adjuvant endocrine therapy consisting of 5 years of tamoxifen therapy in women
      with oestrogen receptor-positive breast cancer. The IES study confirmed that
      switching to an aromatase inhibitor (AI) such as exemestane after 2-3 years of
      tamoxifen therapy resulted in improved survival relative to women remaining on 5
      years of tamoxifen therapy. Data from IES concur with the findings of other
      studies with AIs that support the rationale of switching from tamoxifen to an AI
      after 2-3 years of tamoxifen in postmenopausal women who remain disease-free.

PMID- 18340243
TI  - Statistical analysis in cancer clinical trials.
AB  - Evidence suggests that over the long term (>5 years), tamoxifen should be
      replaced with an agent such as an aromatase inhibitor. Recent decisions to
      terminate several large clinical trials, in view of emerging efficacy data with
      the aromatase inhibitors, indicate that there is a need for guidelines that
      determine when trials should be discontinued. As a result of the interim efficacy
      analysis and subsequent discontinuation of the NCIC MA.17 trial, the National
      Surgical Adjuvant Breast and Bowel Project B-33 study was unblinded after a
      median of 10 months of treatment. The B-33 trial, nevertheless, demonstrated a
      statistically significant improvement in relapse-free survival indicating that
      exemestane is likely to be a valuable treatment option in postmenopausal women
      with early breast cancer who remain disease-free following 5 years of tamoxifen
      therapy.

PMID- 18340244
TI  - Influence of intrahepatic vessels on volume and shape of percutaneous thermal
      ablation zones: in vivo evaluation in a porcine model.
AB  - OBJECTIVES: Aim of the study was to evaluate the precise influence of different
      intrahepatic vessels, vessel sizes, and distances from the applicator on volume
      and shape of hepatic laser ablation zones in an in vivo porcine model. MATERIALS
      AND METHODS: The study was approved by the institutional animal care and use
      committee. Eighteen computed tomography-guided Nd:YAG laser ablations were
      performed in the livers of 10 pigs at varying distances from hepatic veins and
      portal fields. After hepatectomy the livers were cut into 2-mm slices
      perpendicular to the laser applicator axes. For each ablation zone the maximum
      achievable (ideal) volume, the segmented (real) volume, the maximum radius, and
      the radius at the position of adjacent hepatic vessels were determined. The
      shapes of the ablation zones were evaluated qualitatively. Comparative statistics
      using the unpaired t test and a multiple linear regression analysis were
      performed. RESULTS: Ideal and real ablation zone volumes differed by 27.3% (8.6
      +/- 1.5 mL vs. 6.4 +/- 1.1 mL; P < 0.0001). Thirty-eight of 60 (63%) hepatic
      veins versus 28 of 31 (90%) portal veins within the central slices of the 18
      ablation zones led to a reduction of the ablation zone's radius, depending on the
      distance between the vessel and the applicator and the vessel type. Portal fields
      revealed stronger effects than hepatic veins. The vessel diameter showed no
      independent effect (P > 0.05). When influencing, all hepatic veins showed a focal
      indentation whereas portal fields always showed broad flattening of the ablation
      zone. CONCLUSIONS: Portal fields lead to more heat sink than hepatic veins. The
      effects decreased with the distance between vessel and applicator tip, but less
      so for portal fields. The 2 vessel types induced considerably different shape
      alterations of the ablation zones. These results were not dependent on vessel
      size. This should be considered in the planning of thermal tumor ablations.

PMID- 18340245
TI  - Left ventricular postmyocardial infarction remodeling studied by combining MR
      tagging with delayed MR contrast enhancement.
AB  - OBJECTIVES: We sought to monitor the evolution of noninfarcted and infarcted
      myocardium function in the process of left ventricular (LV) remodeling after a
      reperfused myocardial infarction. MATERIAL AND METHODS: Pigs (n = 8) were
      subjected to reperfused infarction. Magnetic resonance imaging (MRI) was
      performed at 3 days and 8 weeks after infarction. Regional circumferential
      shortening (Ecc) and principal strain L1 in the infarcted, peri-infarcted, and
      remote myocardium were evaluated by tagged cine MRI combined with matched late
      enhancement data (Gadolinium-DOTA-enhanced IR-GRE) Global LV function was
      evaluated by cine MRI. Animals were euthanized after the second imaging session
      and tissue samples from the different myocardial regions were obtained for
      histopathologic study. RESULTS: There was a significant deterioration in Ecc
      between the 3-day and 8-week studies in the peri-infarcted myocardium at apex (
      9.9% +/- 4.5% to -6.5 +/- 3.9; P = 0.046) whereas it remained stable for all
      other regions at all levels. A trend toward improvement in Ecc existed in the
      infarcted myocardium when infarction transmurality was less than 50% of the LV
      wall (-7.5% +/- 0.8% to -12.2% +/- 2.9% P = 0.06). Ecc in infarcted myocardium
      was significantly inferior (P < 0.002) to that in remote and peri-infarcted
      myocardium at the apical level (2.7% +/- 2.6% vs. -14.4% +/- 3.3% and -9.9% +/-
      4.5%, respectively). Global LV function substantially deteriorated after
      infarction and was associated with a significant LV dilation. CONCLUSION: These
      results confirm the hypothesis that scarred myocardium imposes additional
      functional burden to the peri-infarcted myocardium.

PMID- 18340246
TI  - Optimization of low-contrast detectability in thin-collimated modern
      multidetector CT using an interactive sliding-thin-slab averaging algorithm.
AB  - OBJECTIVES: To analyze the effects of the sliding-thin-slab averaging algorithm
      on low-contrast performance in MDCT imaging and to find reasonable parameters for
      clinical routine work. MATERIALS AND METHODS: A low-contrast phantom simulating
      hypodense lesions (20 HU object contrast) was scanned with a 16-slice spiral CT
      scanner using different mAs-settings of 25, 50, 100, and 195 mAs. Other scan
      parameters were as follows: tube voltage = 120 kVp, slice collimation = 0.625 mm,
      pitch = 1.375 (high speed), reconstruction interval = 0.5 mm. Images were
      reconstructed with soft, standard, and bone algorithms, resulting in a total of
      12 datasets. A sliding-thin-slab averaging algorithm was applied to these primary
      datasets, systematically varying the slab thickness between 0.5 and 5.0 mm. The
      low-contrast performance of the resulting datasets was semi-automatically
      analyzed using a statistical reader-independent approach: A size-dependent
      analysis of the image noise within the phantom was used to empirically generate a
      contrast discrimination function (CDF). The ratio between the actual contrast and
      the minimum contrast necessary for the detection (as given by the CDF) was
      calculated for all lesions in each dataset and used to evaluate the low-contrast
      detectability of the different lesions at increasing slab thickness. The results
      were compared with the original datasets to calculate the improvement in low
      contrast detectability. RESULTS: Using the sliding-thin-slab algorithm, low
      contrast performance was increased by a factor between 1.1 and 1.7 when compared
      with the primary dataset. The improvement of the visibility index at optimal slab
      thickness when compared with the original slice thickness (0.625 mm) was
      statistically significant (P < 0.05, Student t test) for the following datasets:
      8 mm: all datasets; 6 mm: 25 mAs/soft, 195 mAs/bone, 25 mAs/bone; 5 mm: 25
      mAs/soft, 25 mAs/bone. The ideal slab thickness over all datasets was 43% (+/-3%)
      of the diameter of the lesion to be detected. CONCLUSIONS: The use of an
      interactive sliding-thin-slab averaging algorithm can be readily applied to
      optimize low-contrast detectability in thin-collimated CT datasets. As a general
      rule for daily routine, a slice thickness of approximately 2.5 to 3.0 mm can be
      regarded as a reasonable preset, resulting in an optimized detectability of
      lesions with a diameter of 5 mm and above.

PMID- 18340247
TI  - Gadobenate dimeglumine as a contrast agent for dynamic breast magnetic resonance
      imaging: effect of higher initial enhancement thresholds on diagnostic
      performance.
AB  - RATIONALE AND OBJECTIVE: Gadobenate dimeglumine (Gd-BOPTA), a high-relaxivity
      contrast agent, has been recently proposed for dynamic MR imaging of the breast.
      The objective of this study was to optimize the diagnostic performance of Gd
      BOPTA-enhanced dynamic breast MR imaging by using adjusted initial enhancement
      thresholds. METHODS: Thirty-four patients with 36 breast lesions
      (malignant/benign = 28/8) underwent dynamic breast MRI with 0.1 mmol/kg Gd-BOPTA
      and 120-second time resolution. A score system based on shape (round/oval/lobular
      = 0; linear/dendritic/stellate = 1), margins (defined = 0; undefined = 1),
      pattern (homogeneous = 0; inhomogeneous = 1; rim = 2), kinetics (continuous = 0;
      plateau = 1; washout = 2), and initial enhancement was used. Initial enhancement
      was determined with standard (<50% = 0; 50%-100% = 1; >100% = 2) and adjusted
      (<100% = 0; 100%-240% = 1; >240% = 2) thresholds. Scores of 0 to 3 indicated
      benign lesions and scores of 4 to 8 malignant lesions. Diagnostic performance was
      assessed in terms of sensitivity, specificity, positive and negative predictive
      values, and overall accuracy. RESULTS: The initial enhancement was >100% for 26
      malignant and 7 benign lesions and >240% for 16 and 1 lesions, respectively. The
      overall score was 5.89 +/- 1.34 with standard thresholds and 5.50 +/- 1.53 with
      adjusted thresholds (P = 0.003) for cancers, 4.00 +/- 1.93 and 3.25 +/- 1.75 (P =
      0.028) for benign lesions, respectively. Sensitivity, specificity, positive
      predictive value, negative predictive value, and accuracy was 96%, 13%, 79%, 50%,
      and 78%, respectively, with standard thresholds and 96%, 75%, 93%, 86%, and 92%,
      respectively, with adjusted thresholds. A ductal carcinoma in situ was false
      negative whereas a fat necrosis and a papilloma were false positive with both
      thresholds. Three fibroadenomas, 1 adenosis, and 1 fibrosis were false positive
      with standard thresholds but true negatives with adjusted thresholds.
      CONCLUSIONS: Lesion characterization with Gd-BOPTA requires higher thresholds for
      initial enhancement than those used with conventional Gd-chelates, leading to
      improved specificity, predictive values, and accuracy.

PMID- 18340249
TI  - Reduction of radiation dose estimates in cardiac 64-slice CT angiography in
      patients after coronary artery bypass graft surgery.
AB  - OBJECTIVES: The objectives of this prospective investigation in patients after
      bypass graft surgery were (1) to estimate radiation dose for routine bypass graft
      computed tomography (CT) angiography, (2) to study the impact of anatomically
      adapted and ECG-controlled tube current modulation on radiation dose estimates,
      and (3) effects on qualitative and quantitative image quality parameters.
      METHODS: Radiation dose was estimated for 194 consecutive patients undergoing 64
      slice CT angiography (Somatom Sensation 64 Cardiac, Siemens Medical Solutions).
      The impact of anatomically adapted tube current modulation was studied in 2
      consecutive patients groups. Furthermore, the impact of ECG-controlled tube
      current modulation, applied as indicated, was evaluated in both groups. RESULTS:
      Mean radiation dose estimate for a 64-slice CT bypass graft study was 18.9 +/-
      6.0 mSv (CTDIvol 42.3 +/- 12.9 mGy). The application of anatomically adapted tube
      current modulation had no effect on dose parameters (CTDIvol 43.3 +/- 13.2 vs.
      40.1 +/- 12.1 mGy for those with versus those without anatomically adapted tube
      current modulation, P = 0.1). Additional implementation of ECG-controlled tube
      current modulation resulted in reduced dose parameters (CTDIvol of 32.9 +/- 2.6
      vs. 58.9 +/- 3.9 mGy and radiation dose estimates: 14.7 +/- 1.9 mSv vs. 26.5 +/-
      2.1 mSv for those with versus those without ECG pulsing, both P < 0.01). There
      was no deterioration in image quality with use of tube current modulation
      algorithms. CONCLUSIONS: The radiation burden associated with 64-slice bypass
      graft CT angiographies is substantial. Anatomically adapted tube current
      modulation does not reduce radiation dose parameters, whereas ECG-controlled tube
      current modulation was associated with a 45% reduction in dose estimates.
      Application of both tube current modulation algorithms did not result in reduced
      image quality.

PMID- 18340248
TI  - In vivo vibroacoustography of large peripheral arteries.
AB  - OBJECTIVE: Vibroacoustography allows imaging of objects on the basis of their
      acoustic signal emitted during low-frequency (kHz) vibrations produced by 2
      intersecting ultrasound beams at slightly different frequencies. This study
      tested the feasibility of using vibroacoustography to distinguish between normal
      and calcified femoral arteries in a pig model. MATERIALS AND METHODS: Thirteen
      normal porcine femoral arteries, 7 with experimentally induced arterial
      calcifications, and 1 control artery injected with saline only were scanned in
      vivo. Images were obtained at 45 kHz using a 3 MHz confocal transducer. The
      acoustic emission signal was detected with a hydrophone placed on the animal's
      limb. Images were reconstructed on the basis of the amplitude of the acoustic
      emission signal. Vessel patency, vessel dimensions, and the extent of calcified
      plaques were confirmed in vivo by angiography and conventional ultrasound.
      Excised arteries were reexamined with vibroacoustography, X-ray radiography, and
      histology. RESULTS: In vivo, vibroacoustography produced high-resolution, speckle
      free images with a high level of anatomic detail. Measurements of femoral artery
      diameter were similar by vibroacoustography and conventional ultrasound (mean
      difference +/- SD, 0.1 +/- 0.4 mm). Calcified plaque area measured by different
      methods was comparable (vibroacoustography, in vivo: 1.0 +/- 0.9 cm;
      vibroacoustography in vitro: 1.1 +/- 0.6 cm2; X-ray radiography: 0.9 +/- 0.6
      cm2). The reproducibility of measurements was high. Sensitivity and specificity
      for detecting calcifications were 100% and 86%, respectively, and positive and
      negative predictive values were 77% and 100%, respectively. CONCLUSIONS:
      Vibroacoustography provides accurate and reproducible measurements of femoral
      arteries and vascular calcifications in living animals.

PMID- 18340250
TI  - Black-blood diffusion-weighted EPI acquisition of the liver with parallel
      imaging: comparison with a standard T2-weighted sequence for detection of focal
      liver lesions.
AB  - OBJECTIVES: To evaluate the performance of black-blood diffusion-weighted (DW)
      EPI sequences with parallel imaging for the detection of focal liver lesions in
      comparison with a standard T2-weighted (T2-w) sequence. MATERIALS AND METHODS:
      Twenty patients with known or suspected focal liver lesions underwent liver MRI
      using a DW-EPI sequence with a b-value of 50 S/mm2 (TR/TE 2200/50 ms) and a
      standard fat-saturated T2-w sequence (TR/TE 2800/107 ms) with 6-mm slice
      thickness on a 1.5-T MRI system. Both sequences used parallel imaging with an
      acceleration factor of 2. Overall image quality and degree of artifacts were
      compared on a 5-point scale with 5 being the most desirable score. The detection
      rate and the level of confidence with regard to lesion detection were evaluated
      for both sequences in comparison to a contrast-enhanced (Gadolinium and SPIO) MR
      examination, which was used as the standard of reference. RESULTS: The DW-EPI
      sequence showed significantly (P < 0.05) improved overall image quality (average
      score 4.15 vs. 3.63) and fewer artifacts (average score 4.2 vs. 3.5) in
      comparison with the T2-w sequence. The sensitivity for lesion detection was
      superior in the DW-EPI sequence (83% vs. 61%). The level of confidence in the
      detection of focal liver lesions was also superior for the DW-EPI sequence in
      comparison with the T2-w sequence (average score 3.9 vs. 3.2). CONCLUSIONS: DW
      EPI sequences for liver-imaging are feasible with parallel imaging and show
      excellent image quality. They may contribute to more easy and confident lesion
      detection in comparison with T2-w sequences.

PMID- 18340251
TI  - Pulse repetition time and contrast enhancement: simulation study of Gd-BOPTA and
      conventional contrast agent at different field strengths.
AB  - OBJECTIVES: To investigate theoretically enhancement and optimal pulse repetition
      times for Gd-BOPTA and Gd-DTPA enhanced brain imaging at 0.23, 1.5, and 3.0 T.
      METHODS: The theoretical relaxation times of unenhanced, conventional contrast
      agent (Gd-DTPA) and new generation contrast agent (Gd-BOPTA) enhanced glioma were
      calculated. Then, simulation of the signals and contrasts as a function of
      concentration and pulse repetition time (TR) in spin echo sequence was done at
      0.23, 1.5, and 3.0 T. The effect of echo time (TE) on tumor-white matter contrast
      was also clarified. Three patient cases were imaged at 0.23 T as a test of
      principle. RESULTS: Gd-BOPTA may give substantially better glioma-to-white matter
      contrast than Gd-DTPA but is more sensitive to the length of TR. These
      characteristics are accentuated at 0.23 T. Optimal TR lengths are shorter for Gd
      BOPTA than for Gd-DTPA enhanced imaging at all field strengths. TR optimized for
      Gd-DTPA may thus give suboptimal contrast in Gd-BOPTA enhanced imaging. Higher
      enhancement with Gd-BOPTA is further accentuated by short TE. CONCLUSION:
      Appropriate TRs at 0.23 T appear to be approximately 300 to 400 milliseconds and
      250 to 300 milliseconds, at 1.5 T 500 to 600 milliseconds and 400 to 450
      milliseconds and at 3.0 T 550 to 650 milliseconds and 475 to 525 milliseconds
      using Gd-DTPA and Gd-BOPTA, respectively. For Gd-BOPTA enhanced imaging, it seems
      justified to optimize TR according to contrast and seek options like parallel
      excitation (Hadamard encoding) for increasing the number of slices and SNR.

PMID- 18340252
TI  - Professionals and managers with severe mental illnesses: findings from a national
      survey.
AB  - This study explores the capacity of individuals with severe mental illness to be
      employed in managerial or professional jobs and the correlates of their
      vocational success. Using purposive sampling techniques, we identified a national
      sample of 347 individuals for a mail survey who had succeeded in obtaining and
      retaining mid to upper level managerial or professional positions. The majority
      worked full-time and held their job for more than 2 years. Their vocational
      success was operationalized based on 4 employment outcomes: employment status
      (full-time vs. part-time), job tenure, occupational rank, and annual income. Key
      factors that contributed to respondents' vocational success were lesser severity
      of the illness as indicated by lack of lifetime receipt of disability benefits,
      capacity to manage one's own psychiatric condition, and higher education. Study
      findings point to the role of supported education and self-efficacy in promoting
      the employment outcomes among individuals with severe mental illnesses.

PMID- 18340253
TI  - Relationship between self-focused attention and dissociation in patients with and
      without auditory hallucinations.
AB  - The purpose of this work was to study the relationship between self-focused
      attention and dissociative experiences in 4 groups of subjects: patients with a
      psychotic disorder who suffer from auditory hallucinations, patients with
      psychoses who have recovered from their hallucinations, patients with psychoses
      who have never had them, and a fourth nonclinical group. The private self
      consciousness scale, revised version by Scheier and Carver, J Appl Soc Psychol.
      1985;15:687-699, was used to measure self-focused attention, and the dissociative
      experience scale (DES-II, Bernstein and Putnam, J Nerv Ment Dis. 1986;174:727
      735) was used for dissociation. The results showed that the attention of subjects
      with hallucinations was more self-focused than the nonclinical group, but did not
      differentiate significantly from groups of patients without hallucinations. On
      the other hand, patients with hallucinations and those recovered from them had a
      higher percentage of dissociative experiences than the rest of the groups in the
      total DES-II score and in its 3 factors, dissociative amnesia, depersonalization,
      and absorption. We also found a positive correlation between self-focusing and
      dissociative experiences in subjects with hallucinations. The depersonalization
      factor on the DES-II was the only factor predicting auditory hallucinations. The
      conclusions discuss the relevance of dissociative factors and self-focused
      attention to understanding the etiology of auditory hallucinations and their
      contributions to current cognitive models of hallucinations.

PMID- 18340254
TI  - Heterogeneity in behavioral treatment response in severe mental illness.
AB  - An exploratory investigation of behavioral treatment response during inpatient
      rehabilitation for severe mental illness is presented. Archival data from 26
      weeks of behavioral contingency management (CM) programs targeting treatment
      nonadherence for 2 cohorts of participants were analyzed. For cohort 1 (N = 39),
      a multivariate analysis of longitudinal behavioral data identified 4
      qualitatively and quantitatively distinct patterns of CM response and these
      groups differed in verbal memory ability. Analysis of cohort 2 (N = 45)
      replicated the finding of 4 patterns of CM response. We further clarified
      behavioral heterogeneity in cohort 2 by using hierarchical linear modeling with
      neurocognitive and social cognitive covariates. Results indicated that memory,
      attention, and a high external locus of control (LOC) were associated with level
      of nonadherence at baseline. Reductions in external locus of control were
      associated with greater CM response during the course of rehabilitation.
      Implications for understanding individual responses to the rehabilitation process
      are discussed.

PMID- 18340255
TI  - Dysfunctional attitudes and cognitive schemas in bipolar manic and unipolar
      depressed outpatients: implications for cognitively based psychotherapeutics.
AB  - Dysfunctional thought patterns are presumed to underlie cognitive biases in mood
      disorder patients. However, few studies have compared dysfunctional thought
      patterns in bipolar manic and unipolar depressed patients. Cognitive schemas and
      dysfunctional attitudes were evaluated using the cognitive checklist for mania
      and Dysfunctional Attitudes Scale (DAS) in 34 bipolar manic, 35 unipolar
      depressed, and 29 nonpsychiatric control subjects. Unipolar depressed subjects
      had significantly higher total DAS scores and subfactor scores as compared with
      nonpsychiatric controls, whereas bipolar patients had intermediate scores between
      both groups. Significant correlations emerged between cognitive checklist for
      mania total and subcomponent scores and the DAS (total, performance subfactor,
      and approval subfactor scales) for the bipolar, but not the unipolar or
      nonpsychiatric control groups. Core beliefs among bipolar patients appear
      negativistic during manic phases, potentially reflecting an overcompensation for
      depression. The findings support clinical approaches targeting depressive
      cognitions regardless of the presence of manic symptoms.

PMID- 18340256
TI  - Intensive short-term dynamic psychotherapy for DSM-IV personality disorders: a
      randomized controlled trial.
AB  - This study evaluated the efficacy and long-term effectiveness of intensive short
      term dynamic psychotherapy (ISTDP) in the treatment of patients with DSM-IV
      personality disorders (PD). Twenty-seven patients with PD were randomized to
      treatment with ISTDP or a minimal-contact, delayed-treatment control condition.
      ISTDP-treated patients improved significantly more than controls on all primary
      outcome indices, reaching the normal ranges on both the brief symptom inventory
      (1.51-0.51, p < 0.001) and inventory of interpersonal problems (1.56-0.67, p <
      0.001). When control patients were treated, they experienced benefits similar to
      the initial treatment group. In long-term follow-up, the whole group maintained
      their gains and had an 83.3% reduction of personality disorder diagnoses.
      Treatment costs were thrice offset by reductions in medication and disability
      payments. This preliminary study of ISTDP suggests it is efficacious and cost
      effective in the treatment of PD. Limitations of this study and suggestions for
      future research are discussed.

PMID- 18340257
TI  - The importance of interpersonal treatment goals for depressed inpatients.
AB  - Increased understanding of the treatment goals of depressed patients may lead to
      improved treatments and assist researchers and program evaluators in choosing
      clinically relevant outcome measures. To characterize patients' depression
      treatment goals, we interviewed hospitalized depressed patients about their
      treatment goals. Common responses included improving relationships, decreasing
      sadness or anxiety, and finding a job or improving job performance. On a written
      questionnaire, patients also ranked decreasing suicidal thoughts highly. These
      results suggest that for many severely depressed individuals, primary treatment
      goals include improvements in social and occupational functioning in addition to
      symptomatic improvement.

PMID- 18340258
TI  - Adequacy of, attitudes toward, and adherence to treatments by suicidal and
      nonsuicidal depressed patients.
AB  - We examined differences in treatments received, and attitudes and adherence to
      them between suicidal and nonsuicidal patients with major depressive disorder
      (MDD). Psychiatric MDD patients with no suicidal behavior (N = 92), suicidal
      ideation (N = 92), or attempts (N = 34) were compared during 6 months of follow
      up in the Vantaa Depression Study (VDS). Patients with suicidal behavior received
      antidepressants or adequate antidepressant treatment significantly more often,
      had more frequent appointments with psychiatrists, more psychotherapeutic
      support, and more favorable attitudes toward antidepressant treatment than
      nonsuicidal patients. However, after adjusting for the confounding severity of
      depression, the significance of these differences was lost. Adherence to
      treatment was similar in the patient groups. Overall, among psychiatric patients
      with MDD, those known to be suicidal have higher suicide risk and should receive
      more intensive treatment. However, suicidal behavior per se does not seem to
      markedly influence treatments provided nor should it be associated with negative
      attitudes or poor adherence to treatments.

PMID- 18340259
TI  - Motives for nonsuicidal self-injury among women with borderline personality
      disorder.
AB  - Patients with borderline personality disorder (BPD) are known to use nonsuicidal
      self-injury (NSSI) as a dysfunctional strategy to regulate intense emotions. The
      primary purpose of this study was to clarify the motives for NSSI along with
      their interrelations. We further investigated the variety of emotions preceding
      NSSI and possible effects of NSSI on these emotions. To this end, a structured
      self-rating questionnaire on NSSI was administered to 101 female BPD-patients
      exhibiting NSSI. Most patients reported multiple motives for NSSI. The motives
      were more likely to compound than to exclude one another. Negative reinforcement
      was almost always involved in NSSI, whereas positive reinforcement (e.g.,
      "getting a kick") played an additional role among about half of the patients.
      NSSI was usually preceded by a large variety of negative feelings that were
      reported to clearly improve with NSSI. In conclusion, therapists should
      anticipate a multidimensional functional spectrum when exploring motives of NSSI.

PMID- 18340260
TI  - Crying as a gendered indicator of depression.
AB  - Crying is a gendered activity; women in the general population are known to cry
      more than men. However, crying is also used as a sign of depression. Its use may
      explain some of the discrepancy in rates of depression in men and women. We
      suggest that crying is an invalid indicator because of its gendered status and
      should be removed from the diagnostic criteria for depression. Men may show other
      symptoms when depressed more than women, such as aggression and irritability. The
      inclusion of crying items in depression instruments may therefore introduce a
      gender bias in the assessment of depression.

PMID- 18340261
TI  - Influence of negative cognition on the parental bonding instrument (PBI) in
      patients with major depression.
AB  - The aim of this study was to examine the effects of negative cognition on PBI
      score before and after treatment for depression. Forty major depressive disorder
      outpatients were assessed with the PBI scale and Structured Interview Guide for
      Hamilton Rating Scale for Depression (SIGH-D) at the time of the first medical
      examination (baseline) and 8 weeks later. The SIGH-D scores decreased by about
      50% from baseline to 8 weeks, but there was no significant change in the PBI
      scores of the depressed outpatients from baseline to 8 weeks. Analysis of
      covariance with the SIGH-D scores as covariate was conducted for PBI scores
      between baseline and 8 weeks to remove effects of MDD. No significant differences
      were found on any of the PBI scales. Even though the therapeutic values on the
      SIGH-D of the depressed patients indicated that depressive symptoms were reduced
      by about 50%, depression level did not influence the PBI scores. This study
      provides evidence for the stability of parental representations throughout
      treatment, as measured by the PBI.

PMID- 18340262
TI  - Religion, spirituality, and depression in adolescent psychiatric outpatients.
AB  - This study examines in a preliminary manner the relationship between multiple
      facets of religion/spirituality and depression in treatment-seeking adolescents.
      One hundred seventeen psychiatric outpatients aged 12 to 18 completed the brief
      multidimensional measure of religiousness/spirituality, the Beck Depression
      Inventory (BDI), a substance abuse inventory. Controlling for substance abuse and
      demographic variables, depression was related to feeling abandoned or punished by
      God (p < 0.0001), feeling unsupported by one's religious community (p = 0.0158),
      and lack of forgiveness (p < 0.001). These preliminary results suggest that
      clinicians should assess religious beliefs and perceptions of support from the
      religious community as factors intertwined with the experience of depression, and
      consider the most appropriate ways of addressing these factors that are sensitive
      to adolescents' and families' religious values and beliefs.

PMID- 18340263
TI  - Difficulty identifying feelings predicts the persistence of trauma symptoms in a
      sample of veterans who experienced military sexual trauma.
AB  - The current study examined the prospective association between alexithymia and
      the persistence of trauma symptoms in a clinical sample of 175 male and female
      veterans who experienced sexual trauma during military service (military sexual
      trauma; MST). Trauma symptoms decreased significantly over the course of a
      specialized residential treatment program. Difficulty identifying feelings was
      related to persistence of the following trauma symptoms: overall symptoms, sexual
      abuse trauma symptoms, dissociative symptoms, and anxiety. Men exhibited more
      persistent symptoms overall, more persistent sexual problems, and more sexual
      abuse trauma symptoms compared with women (over and above controlling for
      symptoms at intake). The results speak to the significant role that difficulty
      identifying feelings has in the treatment of PTSD. In addition, the results
      suggest that MST has different implications for men compared with women.
      Specifically, men who were sexually abused in the military experienced greater
      persistence of symptoms compared with women, especially in the areas of sexual
      functioning.

PMID- 18340268
TI  - Continuous EEG monitoring during thrombolysis in acute hemispheric stroke
      patients using the brain symmetry index.
AB  - Continuous EEG monitoring could benefit stroke patients as it may detect changes
      in brain function in a possible reversible state, allowing early intervention.
      The Brain Symmetry Index (BSI) was introduced previously as a measure to quantify
      ischemia in acute hemispheric stroke patients, and a positive correlation was
      found between the BSI and the National Institutes of Health Stroke Scale. Here,
      we explore the feasibility and potential clinical relevance of continuous EEG
      monitoring in acute hemispheric stroke, with the BSI as an indicator of the
      effect of thrombolysis with recombinant tissue plasminogen activator (r-tPA).
      Patients with acute hemispheric stroke treated with r-tPA were monitored using a
      bipolar eight channel EEG. The BSI is defined as the mean of the absolute value
      of the difference in the mean hemispheric amplitude spectrum; values range from 0
      (no asymmetry) to 1 (maximal asymmetry). The clinical condition of the patients
      was assessed with the National Institutes of Health Stroke Scale. In this pilot
      study 16 patients were included. In all patients, the BSI remained constant or
      showed improvement during and after treatment with r-tPA. The correlation between
      the BSI and National Institutes of Health Stroke Scale in this study is
      significant, and confirms previous results. The correlation between the change in
      BSI and the change in National Institutes of Health Stroke Scale during treatment
      with r-tPA is significant, as well. No clinical significant complications
      occurred during r-tPA treatment. Our results show that continuous EEG monitoring
      using the BSI is technically feasible and provides real-time information about
      the effect of thrombolysis in acute hemispheric stroke patients.

PMID- 18340269
TI  - Persistent suppression of postexercise facilitation of motor evoked potentials
      during alternate phases of bipolar disorder.
AB  - The current study sought to longitudinally evaluate the postexercise facilitation
      of motor evoked potentials (MEP) in two patients during different phases of short
      circle depressive-manic disorder. Each study included 50 baseline MEP elicited by
      transcranial magnetic stimulation, followed by 50 MEP immediately after
      nonfatiguing exercise of the examined muscle. Postexercise MEP facilitation,
      expressed as percentage of baseline value, varied from 71% to 119% and from 99%
      to 107% in each patient, respectively, being significantly lower than our mean
      normal control value (268%). No differences in MEP facilitation between phases of
      short-circle depressive-manic disorder were revealed. Reduced postexercise
      facilitation was independent of the bipolar disorder phases, suggesting an
      invariable underlying association of the psychiatric pathophysiological
      mechanisms to impaired cortical excitability.

PMID- 18340270
TI  - The colorful brain: visualization of EEG background patterns.
AB  - This article presents a method to transform routine clinical EEG recordings to an
      alternative visual domain. The method is intended to support the classic visual
      interpretation of the EEG background pattern and to facilitate communication
      about relevant EEG characteristics. In addition, it provides various quantitative
      features. The EEG features used in the transformation include color-coded time
      frequency representations of two novel symmetry measures and a synchronization
      measure, based on a nearest-neighbor coherence estimate. This triplet captures
      three highly relevant aspects of the dynamics of the EEG background pattern,
      which correlate strongly with various neurologic conditions. In particular, it
      quantifies and visualizes the spatiotemporal distribution of the EEG power in the
      anterioposterior and lateral direction, and the short-distance coherence. The
      potential clinical use is illustrated by application of the proposed technique to
      various normal and abnormal EEGs, including seizure activity and the transition
      to sleep. The proposed transformation visualizes various essential elements of
      EEG background patterns. Quantitative analysis of clinical EEG recordings and
      transformation to alternative domains assists in the interpretation and
      contributes to an objective interpretation.

PMID- 18340271
TI  - Determination of subthalamic nucleus location by quantitative analysis of
      despiked background neural activity from microelectrode recordings obtained
      during deep brain stimulation surgery.
AB  - Microelectrode recording during deep brain stimulation surgery is a useful
      adjunct for subthalamic nucleus (STN) localization. We hypothesize that
      information in the nonspike background activity can help identify STN boundaries.
      We present results from a novel quantitative analysis that accomplishes this
      goal. Thirteen consecutive microelectrode recordings were retrospectively
      analyzed. Spikes were removed from the recordings with an automated algorithm.
      The remaining "despiked" signals were converted via root mean square amplitude
      and curve length calculations into "feature profile" time series. Subthalamic
      nucleus boundaries determined by inspection, based on sustained deviations from
      baseline for each feature profile, were compared against those determined
      intraoperatively by the clinical neurophysiologist. Feature profile activity
      within STN exhibited a sustained rise in 10 of 13 tracks (77%). The sensitivity
      of STN entry was 60% and 90% for curve length and root mean square amplitude,
      respectively, when agreement within 0.5 mm of the neurophysiologist's prediction
      was used. Sensitivities were 70% and 100% for 1 mm accuracy. Exit point
      sensitivities were 80% and 90% for both features within 0.5 mm and 1.0 mm,
      respectively. Reproducible activity patterns in deep brain stimulation
      microelectrode recordings can allow accurate identification of STN boundaries.
      Quantitative analyses of this type may provide useful adjunctive information for
      electrode placement in deep brain stimulation surgery.

PMID- 18340272
TI  - The interaction between somatosensory and auditory cognitive processing assessed
      with event-related potentials.
AB  - Event-related potentials induced by somatosensory and after auditory stimulation
      or bilateral somatosensory stimulation in young adults were studied, aiming to
      evaluate interactions of cognitive processing of somatosensory and auditory
      information. In experiment 1, event-related potentials were elicited by four
      stimulus conditions which were randomly presented with an interstimulus interval
      of 20 +/- 3 milliseconds: electric stimuli delivered to the right median nerve
      (Con 1), auditory stimuli delivered to both ears (Con 2), electric and subsequent
      auditory stimuli (Con 3), and electric stimuli delivered to the bilateral median
      nerve (Con 4). In experiment 2, Con 2 was changed to electric stimulation of the
      left median nerve. The subtraction of grand averaged event-related potentials of
      Con 1 and Con 2 from those of Con 3 demonstrated a positive-negative peak complex
      with a positive peak at approximately 165 to 170 milliseconds after stimuli and a
      negative peak with a mean latency of 372 milliseconds in experiment 1. In
      experiment 2, the subtraction of event-related potentials in Con 1 and 2 from
      those in Con 4 revealed positive and negative peaks resembling those in
      experiment 1, but the distribution or latencies of the peaks differed from those
      in experiment 1. We speculate that the subtracted positive and negative peaks
      reflect different cognitive processing of bimodal and bifocal sensory
      information.

PMID- 18340273
TI  - Two types of remote propagation in mesial temporal epilepsy: analysis with scalp
      ictal EEG.
AB  - The purpose of this study was to describe the propagation pattern of ictal
      discharges, particularly remote patterns from a localized onset in patients with
      mesial temporal epilepsy, and to determine whether this provides additional
      information to that obtained from prolonged presurgery scalp EEG monitoring. This
      is a retrospective and analytical study that included a historical open cohort of
      18 patients with mesial temporal epilepsy, among whom 56 regionalized-lateralized
      onset seizures were recorded. These seizures were analyzed as to whether remote
      propagation occurred and as to their temporal characteristics. Thirty-eight
      regionalized-lateralized onset seizures did not show remote propagation, whereas
      18 did. Two types of remote propagation were identified, one early and one late,
      depending on whether the remote propagation occurred before or after 10 seconds
      had elapsed from the onset of the electroencephalographic seizure. When the
      seizures were compared according to the type of propagation, those with early
      remote propagation showed a correlation, not statistically significant, with the
      intractability of the epilepsy (P = 0.0754), toward independent bitemporal
      interictal discharges (P = 0.1667), and from the MRI perspective, to occur with
      temporal lesions other than pure mesial sclerosis (P = 0.6329). Early remote
      propagation seizures were not associated with nonlateralized onset (P = 0.2682).
      The only patient in our study with switch of lateralization seizures experienced
      early remote propagation seizures. Patients with late remote propagation seizures
      and those without remote propagation showed no statistically significant
      differences with respect to these variables. Ictal recording with scalp EEG
      allows for differentiating between early and late remote propagation in patients
      with mesial temporal epilepsy and regionalized-lateralized onset seizures. Early
      remote propagation probably identifies a subgroup of these patients with greater
      uni- or bitemporal hyperexcitability.

PMID- 18340274
TI  - EEG markers of future cognitive performance in the elderly.
AB  - This exploratory follow-up study investigated whether EEG parameters can predict
      future cognitive performance. Forty elderly subjects, ranging from cognitively
      unimpaired to those with Alzheimer disease underwent EEG registration at baseline
      and neuropsychological examination at both baseline and follow-up. We assessed
      relations between EEG measures and future cognitive performance (i.e., global
      cognition, memory, language, and executive functioning) controlling for age,
      follow-up time, and baseline cognitive performance. Regression models were
      constructed to predict performance on the Cambridge Cognitive Examination, a
      widely used tool within dementia screenings. Baseline EEG measures, i.e.,
      increased theta activity (4-8 Hz) during eyes closed and less alpha reactivity (8
      13 Hz) during eyes open and memory activation, indicated lower global cognitive,
      language (trend significant), and executive performance at follow-up. A
      regression model combining baseline cognitive and EEG measures provided the best
      prediction of future Cambridge Cognitive Examination performance (93%). EEG and
      cognitive measures alone predicted, respectively, 43% and 92% of variance. EEG
      and cognitive measures combined provided the best prediction of future cognitive
      performance. Although the "cognition only" model showed similar predictive power,
      the EEG provided significant additional value. The added value of EEG
      registration in the diagnostic work-up of dementia should be further assessed in
      larger samples.

PMID- 18340275
TI  - Limb temperature and nerve conduction velocity during warming with hot water
      blankets.
AB  - Electrodiagnostic assessments of the peripheral nervous system often require limb
      warming. The traditional warming method, the hot water bath, has several
      disadvantages. We present an alternative: hot water blankets containing
      circulating water of a constant temperature. In addition to having practical
      advantages, these blankets allow for accurate and continuous monitoring of limb
      temperature and nerve conduction velocity (NCV) during warming. We therefore
      aimed to determine (1) the temperature dependence of the NCV of the median motor
      and sensory nerve, deep peroneal nerve, and sural nerve during warming with
      blankets, and (2) the optimal warming strategy for clinical purposes. We warmed
      the limbs of 10 subjects for 90 minutes with blankets set at a temperature of 41
      degrees C. During warming, the NCV of the three nerves and distal motor latency
      of the two motor nerves were measured every 2(1/2) minutes. After 25 minutes of
      warming from an initial temperature of 28 degrees C, the NCV and distal motor
      latency of all nerves were within the normal range. However, after median nerve
      warming until a predefined temperature of 34 degrees C (i.e., for 17 minutes on
      average), two of nine subjects showed abnormal NCVs. We therefore conclude that
      for limb warming with hot water blankets, a fixed 25-minute warming period is
      optimal.

PMID- 18340276
TI  - Yield of the sural/radial ratio versus the medial plantar nerve in sensory
      neuropathies with a normal sural response.
AB  - The electrodiagnostic yield of the medial plantar nerve action potential (NAP)
      amplitude versus the sural/radial amplitude ratio (SRAR) was determined in 110
      consecutive patients with clinically diagnosed distal sensory polyneuropathy (SN)
      and normal sural responses. Forty-five consecutive patients with clinically
      diagnosed lumbosacral radiculopathy served as disease controls. Of the 110 SN
      patients, 32 were classified clinically as SN with large-fiber involvement (SN
      LFI), whereas 78 had clinically pure small-fiber SN. Plantar NAP amplitudes were
      abnormal in 18 of 32 patients (56%) with SN-LFI, and 15 of 78 (19%) with small
      fiber SN. A SRAR <0.21 (fifth percentile of normal) was found in 7 of 32 patients
      (22%) with SN-LFI and 8 of 78 (10%) with small-fiber SN. In the control group,
      the medial plantar NAP was normal in all 45 subjects (100%), whereas the SRAR was
      >0.21 in 43 subjects (96%). Thus, for a 50% pretest probability of SN-LFI, the
      positive predictive value of an abnormal medial plantar was 100% versus 85% for a
      SRAR <0.21. The medial plantar NAP amplitude is a more useful measure of SN, than
      is the SRAR, in patients under age 70, with suspected SN-LFI. The yield of the
      SRAR and plantar NAP amplitude is poor when clinical signs of large-fiber sensory
      dysfunction are lacking.

PMID- 18340277
TI  - United States Pharmacopeia review of the black cohosh case reports of
      hepatotoxicity.
AB  - OBJECTIVE: Black cohosh [Actaea racemosa L., formerly Cimicifuga racemosa (L.)
      Nutt.] is a botanical used mainly for the management of menopausal symptoms.
      Recently, regulatory agencies in Australia, Canada, and the European Union have
      released statements regarding the "potential association" between black cohosh
      and hepatotoxicity. In response, the Dietary Supplement Information Expert
      Committee of the US Pharmacopeia's Council of Experts reviewed safety information
      for black cohosh products. DESIGN: The Expert Committee analyzed information from
      human clinical case reports, adverse event reports, animal pharmacological and
      toxicological data, historical use, regulatory status, and contemporaneous extent
      of use. Reports were obtained from diverse sources, including the European
      Medicines Agency, Health Canada, the Australian Therapeutic Goods Administration,
      and the US Food and Drug Administration. Case reports pertaining to liver damage
      were evaluated according to the Naranjo causality algorithm scale. RESULTS:
      Thirty nonduplicate reports on use of black cohosh products concerning liver
      damage were analyzed. All the reports of liver damage were assigned possible
      causality, and none were probable or certain causality. The clinical
      pharmacokinetic and animal toxicological information did not reveal unfavorable
      information about black cohosh. CONCLUSIONS: Based on this safety review, the
      Dietary Supplement Information Expert Committee determined that black cohosh
      products should be labeled to include a cautionary statement. This is a change
      from the Expert Committee's decision of 2002, which required no such statement.
      With this decision, the US Pharmacopeia's Botanical Expert Committee may develop
      monographs for black cohosh, and the US Pharmacopeia may offer its verification
      programs to dietary supplement ingredient and product manufacturers.

PMID- 18340278
TI  - Transdermal estradiol reduces F2alpha-isoprostane levels in postmenopausal women.
AB  - OBJECTIVE: F2alpha-isoprostanes are considered the most reliable index of in vivo
      oxidative stress. Given the implication of oxidative stress in the pathogenesis
      of atherosclerosis, we investigated the effects of hormone therapy on the plasma
      levels of F2alpha-isoprostanes. DESIGN: Sixty-one healthy postmenopausal women
      were treated in a randomized trial with estradiol either orally (2 mg/day, 28
      women) or transdermally (50 mug/day, 33 women) for 4 weeks. Then women in each
      group were randomly assigned to oral progestogen, either micronized progesterone
      (300 mg/day) or medroxyprogesterone acetate (5 mg/day) for 2 additional weeks.
      Plasma samples were collected before and at the end of each treatment period,
      either estradiol alone or estradiol plus progestogen. F2alpha-isoprostanes were
      measured by a commercial enzyme immunoassay. RESULTS: A significant reduction in
      the levels of F2alpha-isoprostanes was detected only in women receiving
      transdermal estradiol, alone or in combination with medroxyprogesterone acetate.
      CONCLUSIONS: Transdermal estradiol alone or associated with medroxyprogesterone
      acetate decreased plasma levels of F2alpha-isoprostanes. These data elucidate
      additional details of the beneficial effect of estradiol on oxidative stress, a
      relevant mechanism in atherogenesis.

PMID- 18340279
TI  - Endogenous sex hormones and subclinical atherosclerosis.

PMID- 18340280
TI  - Adiposity and hot flashes: one more tree in the forest.

PMID- 18340282
TI  - Letter from Eugene Braunwald.

PMID- 18340283
TI  - Critical Pathways in Cardiology: a journal of evidence-based medicine:
      translating evidence into practice.

PMID- 18340284
TI  - Management of atrial fibrillation.

PMID- 18340285
TI  - Critical pathway for unstable angina and non-ST elevation myocardial infarction:
      February 2002.

PMID- 18340286
TI  - Assessment of compliance with the American College of Cardiology/American Heart
      Association guidelines for patients with acute coronary syndromes admitted to a
      tertiary care hospital coronary care unit.

PMID- 18340287
TI  - Venous thromboembolism guidebook.
AB  - This venous thromboembolism guidebook incorporates evolving contemporary concepts
      in diagnosis and management of pulmonary embolism (PE) and deep venous thrombosis
      (DVT) into a user-friendly menu. The purpose of this document is to provide a
      literature-based review of the current clinical approach to venous
      thromboembolism and up-to-date references for further study in this important
      topic.

PMID- 18340288
TI  - Underutilization of evidence-based medications in acute ST elevation myocardial
      infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 9
      Registry.
AB  - The TIMI 9 Registry set out to assess the management strategies and outcomes of
      an unselected group of patients with acute myocardial infarction presenting with
      ST segment elevation (STEMI). Demographic, procedural, and outcome data were
      collected from 840 consecutive patients with STEMI at 20 hospitals in United
      States and Canada between February and September 1994. Of them, 60% were treated
      with thrombolytic therapy, 9% with primary angioplasty, and 31% did not receive
      reperfusion therapy. Patients who did not receive reperfusion therapy were older,
      more likely female, and had a higher prevalence of prior myocardial infarction,
      congestive heart failure, higher Killip class on admission, and longer time from
      onset of symptoms to presentation. In evaluating the standard contraindications
      for fibrinolysis, approximately 10% in the thrombolytic group, 40% in the primary
      percutaneous coronary intervention (PCI), and 34% of those not receiving
      reperfusion therapy had at least one of these characteristics. Of those patients
      treated with fibrinolysis, only 20% met the National Heart Attack Alert Program
      goal of door-to-drug time < or =30 minutes. Likewise, of those treated with
      primary PCI, only 30% had PCI performed within < or =90 minutes. In-hospital
      mortality was significantly higher for patients not treated with reperfusion
      therapy (18.9%), compared with patients treated with fibrinolysis (7.6%) and
      those treated with primary PCI (10.5%) (P < 0.001). Thus, we found that
      reperfusion therapy was underused, with only 69% of patients with STEMI receiving
      this proven treatment, and of those only 25% treated within the recommended
      timeline. These data suggest that there is room for improvement in the management
      of these patients.

PMID- 18340289
TI  - How to develop a critical pathway: the acute coronary syndromes: Acute Cardiac
      Team to Implement Optimal Treatments Now (ACS ACTION) Program.

PMID- 18340290
TI  - "Act in Time to Heart Attack Signs" action plan: a patient-based critical
      pathway.
AB  - "Act in Time to Heart Attack Signs" provides various educational materials for
      health care providers, heart attack patients, and the public. These include a
      booklet, an educational video, and new Web pages, which can be reached through
      the National Heart, Lung, and Blood Institute website:
      http://www.nhlbi.nih.gov/actintime.

PMID- 18340291
TI  - Algorithms for using B-type natriuretic peptide levels in the diagnosis and
      management of congestive heart failure.

PMID- 18340292
TI  - Critical pathways for primary angioplasty in acute myocardial infarction at
      community hospitals without cardiac surgery.

PMID- 18340293
TI  - A successful strategy to improve door-to-balloon times in acute myocardial
      infarction: a single center experience.

PMID- 18340294
TI  - Critical pathway for acute ST-segment elevation myocardial infarction: estimating
      its potential impact in the TIMI 9 Registry.
AB  - BACKGROUND: Physicians are under increasing pressure to reduce costs and maintain
      high quality of care. Critical pathways may help accomplish this goal. METHODS:
      We assessed the potential impact of implementation of a critical pathway in the
      Thrombolysis in Myocardial Infarction (TIMI 9) Registry, in which 840 consecutive
      patients with ST-elevation myocardial infarction (STEMI) were enrolled at 20
      hospitals in the United States and Canada. The proposed critical pathway targets
      100% use of fibrinolysis in fibrinolytic-eligible patients, 95% use of aspirin,
      and 90% use of beta-blockers and angiotensin-converting enzyme inhibitors (ACE-I)
      and incorporates a strategy of early hospital discharge for low-risk patients.
      Risk reduction for each intervention was estimated based on the benefits seen in
      large randomized controlled clinical trials or meta-analysis. RESULTS: In the
      TIMI 9 Registry, fibrinolysis was used in 60% of the patients; primary
      percutaneous coronary intervention, in 9%; and no reperfusion therapy, in 31%.
      Only 87% of the registry patients took aspirin during hospitalization. Of those
      with documented left ventricular dysfunction or congestive heart failure, 32%
      were discharged on ACE-I; and of those with normal ejection fraction and no
      evidence of congestive heat failure, only 58% were treated with beta-blockers at
      discharge. For early benefit and by increasing the use of reperfusion therapy and
      aspirin to 95% and improving the time to treatment, one could potentially save 13
      lives per 1,000 patients treated per year. Similarly, if beta-blocker and ACE-I
      use increased up to 90% for the long term, almost 2 lives per 1,000 patients
      treated per year could potentially be saved. In summary, by expanding the use of
      a critical pathway for thrombolysis in STEMI, 15 lives per 1,000 patients treated
      per year could be saved. To evaluate the potential economic impact of this
      critical pathway on low-risk patients, 358 of 505 thrombolysis patients had no
      recurrent ischemia, MI, shock, or congestive heart failure through day 5. Their
      median length of stay was 6.7 days (25-75th percentiles, range, 4.8-10.3 days),
      with 73% staying in-hospital more than the target of 5 days, with similar
      findings for patients treated with primary angioplasty. CONCLUSIONS: These
      findings demonstrate that significant opportunities exist for improving medical
      management of patients with acute MI. Critical pathways may help reduce costs
      while improving quality of care.

PMID- 18340295
TI  - Palm Pilot programs to improve quality of care in acute coronary syndromes.

PMID- 18340296
TI  - Smoking cessation.

PMID- 18340297
TI  - A practical guide to understanding the 2002 ACC/AHA guidelines for the management
      of patients with non-ST segment elevation acute coronary syndromes.

PMID- 18340298
TI  - Assessing the effect of publication of clinical guidelines on the management of
      unstable angina and non-ST elevation myocardial infarction in the TIMI III (1990
      1993) and the GUARANTEE (1995-1996) Registries.
AB  - BACKGROUND: The clinical guidelines for unstable angina (UA) and non-ST elevation
      myocardial infarction (NSTEMI) published in 1994 by the Agency for Health Care
      Policy Research (AHCPR) were intended to help improve treatment. No large study,
      however, has evaluated the effect of the guidelines on clinical practice METHODS:
      We compared the treatment of 3,318 patients admitted with UA/NSTEMI in the
      preguideline Thrombolysis in Myocardial Infarction (TIMI) III Registry (1990
      1993) and 2,948 patients enrolled in the postguideline Global Unstable Angina
      Registry and Treatment Evaluation (GUARANTEE) Registry (1995-1996). RESULTS: More
      patients in GUARANTEE received guideline-recommended medication than did those in
      TIMI III, specifically beta-blockers (50.9% vs. 40.7%, P < 0.001), heparin (63.3%
      versus 57.5%, P < 0.001), and the combination of aspirin, heparin, and beta
      blockers on admission plus aspirin at discharge (26.9% vs. 18.8%, P < 0.001).
      These changes were similar in all subgroups, but the greatest improvement in
      medication use was seen in patients admitted to a tertiary care hospital and in
      those with a final diagnosis of NSTEMI, i.e., with positive cardiac markers.
      Conversely, fewer patients in GUARANTEE who fulfilled AHCPR criteria for
      catheterization underwent the procedure (62.3% in GUARANTEE tertiary centers vs.
      44.6% in GUARANTEE nontertiary centers vs. 66.0% in TIMI, P < 0.001). CONCLUSION:
      After publication of clinical guidelines for UA/NSTEMI, more patients received
      appropriate pharmacologic treatment, but a significant number of patients
      remained under-treated. Efforts to improve compliance with guideline
      recommendations via education and critical pathways are warranted, especially in
      nontertiary care settings.

PMID- 18340299
TI  - Use of intraaortic balloon counterpulsation in patients with acute myocardial
      infarction who present to community hospitals.

PMID- 18340301
TI  - Critical pathways: hypertension.

PMID- 18340300
TI  - Low molecular weight heparin use in percutaneous coronary intervention.

PMID- 18340302
TI  - Prodromal symptom recognition of a heart attack: an overlooked phenomenon for
      recognizing a window of opportunity for early heart attack care.

PMID- 18340303
TI  - Early heart attack warning signs.

PMID- 18340304
TI  - Pathway development.

PMID- 18340305
TI  - Strategy for developing a hospital affiliated ambulatory care medical emergency
      response team: is it worth a nickel to try to save a life?
AB  - Health care facilities should reassess their resuscitation team response
      strategies in light of the shift in care from inpatient to outpatient facilities.
      This article discusses a strategy for assessing a health care facility's
      resuscitation needs globally, including a detailed analysis of the physical
      layout, population requiring coverage, personnel, and equipment. Resuscitation
      system design is reviewed, with particular emphasis on training, equipment,
      process variables, administration, cost, and quality improvement. Widespread
      training of nurse-first responders in the use of automated external
      defibrillators along with an in-hospital or community emergency medical services
      advanced life-support response is a cost-effective way of providing tiered
      coverage to remote outpatient facilities or satellite units.

PMID- 18340306
TI  - Management of unstable angina.

PMID- 18340307
TI  - Best practice acute coronary syndromes: integration of a multidisciplinary
      healthcare delivery model.

PMID- 18340308
TI  - Commentary.

PMID- 18340309
TI  - Outcome of patients with acute coronary syndrome admitted to hospitals with or
      without onsite cardiac catheterization laboratory: a TACTICS-TIMI 18 substudy.
AB  - In the TACTICS-TIMI-18 trial, patients with acute coronary syndrome were treated
      with aspirin, heparin, and tirofiban and were randomized to an invasive strategy
      with routine catheterization or to a conservative strategy with catheterization
      (only if the patient had objective evidence of ischemia). Eighty-two of 2,220
      patients were treated in 13 peripheral hospitals without an onsite
      catheterization laboratory. Tirofiban was administered to the peripheral hospital
      group (which was treated invasively) for 28.4 hours before coronary angiography,
      compared with 20.6 hours in the tertiary center group (P = 0.01). There is a
      similar trend in outcomes with benefit of invasive therapy among patients treated
      in peripheral and tertiary hospitals, without increase risk of major bleeding.

PMID- 18340310
TI  - Computer-based clinical guidelines.

PMID- 18340311
TI  - Long-term experience with a contractility (autonomic nervous system) driven
      pacemaker sensor in patients with chronic chagasic cardiomyopathy.
AB  - We analyzed performance of a ventricle-paced, ventricle-sensed, inhibited, rate
      responsive (VVIR) pacemaker driven by autonomic nervous system activity sensor in
      chagasic patients with cardiac conduction system disturbances. Forty-seven
      chagasic patients were studied (28 male, 19 female; age, 24-68 years). Thirty-six
      patients had complete atrioventricular (AV) block, eight had second-degree AV
      block, and the remaining three patients had sinus node disease. Patients were
      divided into two groups according to their heart rate (HR) at rest: group 1 had
      an HR more than 65 bpm; group 2, HR less than 65 bpm. A comparative study that
      extended over the first 12 months after pacemaker implantation evaluated: HR at
      rest and during various types of stress tests, arterial blood pressure at rest
      and during exercise, and performance of the TIR-60 UP leads in conjunction with
      the sensor function as compared with the performance of other leads. Patients
      from group 1 had a higher HR at rest and a smaller HR variation during stress
      test than did patients from group 2. This indicates that with this type of rate
      adaptive system it is possible to control each patient individually. The blood
      pressure at rest and during stress tests did not differ between the two patient
      groups. With respect to the sensor function, the TIR-60 UP leads offered the same
      performance as others leads. The VVIR pacemaker equipped with the sensor of
      autonomic nervous system activity allowed chagasic patients to restore their
      physiologic mechanisms. Seventy-four percent of the patients had the New York
      Heart Association Functional Class improved by 1 or 2 steps, after the pacemaker
      implantation.

PMID- 18340312
TI  - Use of enoxaparin in patients undergoing percutaneous coronary intervention.
AB  - Recent large-scale trials have demonstrated superior clinical outcomes associated
      with the use of enoxaparin in patients with acute coronary syndromes and have led
      to its incorporation into the recent American College of Cardiology/American
      Heart Association guidelines for the management of patients with unstable
      angina/non-ST elevation myocardial infarction. Despite clinical trial evidence,
      questions arise as to how best to manage patients who have received subcutaneous
      enoxaparin who may then require subsequent coronary intervention. We present four
      potential management strategies for handling the transition of these patients to
      the catheterization laboratory and specific dosing recommendations for the use of
      enoxaparin in these circumstances.

PMID- 18340313
TI  - Critical pathway for cardiac rehabilitation after percutaneous coronary
      intervention.

PMID- 18340314
TI  - The American College of Cardiology-National Cardiovascular Data Registry (ACC
      NCDR): a must for all hospitals with cardiovascular programs.

PMID- 18340315
TI  - A comprehensive cardiac rehabilitation program in post-CABG patients: a rationale
      and critical pathway.

PMID- 18340316
TI  - Quality improvement tools designed to improve adherence to the ACC/AHA Guidelines
      for the care of patients with non-ST-segment acute coronary syndromes: the
      CRUSADE quality improvement initiative.

PMID- 18340317
TI  - The critical pathways of an anticoagulation service.

PMID- 18340318
TI  - Body surface mapping: potential role in a chest pain critical care pathway.
AB  - Recent advances in biomarkers have improved the evaluation of patients with acute
      chest pain, but current critical care pathways may still lead to important delays
      in early diagnosis and, hence, treatment of acute myocardial infarction (AMI).
      Electrocardiographic changes may occur within seconds of an ischemic insult, but
      the conventional 12-lead electrocardiogram (ECG) typically has only 50% to 60%
      sensitivity for diagnosis of AMI. Recording of multiple ECGs over a larger
      thoracic surface area, including the right ventricular, high left lateral, and
      posterior regions, by body surface mapping (BSM) has been made feasible in the
      setting of acute coronary syndromes by novel developments in electrode technology
      and simultaneous multichannel ECG data acquisition. Clinical studies of an Food
      and Drug Adminstration-approved BSM system (PRIME-ECG) have demonstrated improved
      early diagnosis of AMI in patients without 12-lead ST elevation and improved
      detection of right ventricular or posterior involvement in ST elevation MI. The
      improved diagnostic sensitivity compared with the conventional 12-lead ECG
      coupled with the potential reduction of delay to diagnosis compared with
      biomarkers suggest that BSM may have an important role as part of a chest pain
      critical care pathway for evaluation of patients with ischemic type chest pain.

PMID- 18340319
TI  - Commentary.

PMID- 18340320
TI  - Foreword to lessons learned.

PMID- 18340321
TI  - Lessons learned from clinical trials: a roundtable discussion.

PMID- 18340322
TI  - In-hospital initiation of cardiovascular protective therapies to improve
      treatment rates and clinical outcomes: the University of California-Los Angeles,
      Cardiovascular Hospitalization Atherosclerosis Management Program.
AB  - Despite the scientific evidence that secondary prevention medical therapies
      reduce mortality in patients with established atherosclerosis, these therapies
      continue to be underused in patients receiving conventional care. To address this
      issue, the University of California, Los Angeles, Cardiovascular Hospitalization
      Atherosclerosis Management Program was implemented in 1994. This hospital-based
      system focused on initiation of antiplatelet therapy, beta-blocker, angiotensin
      converting enzyme inhibitor, and statin therapy (irrespective of baseline low
      density lipoprotein cholesterol) in conjunction with diet and exercise counseling
      in patients hospitalized with coronary artery and other atherosclerotic vascular
      disease. Preprinted orders, critical pathways, discharge forms, physician and
      nursing education, pocket cards, patient educational material, and treatment
      utilization reports facilitated program implementation. Statin use at the time of
      discharge increased from 6% before initiation of the program to 86% after the
      Cardiovascular Hospitalization Atherosclerosis Management Program was implemented
      (P < 0.001). Improved use of aspirin, beta-blockers, and angiotensin-converting
      enzyme inhibitors was also observed. Importantly, in-hospital initiation of
      cardiovascular protective therapies had a dramatic effect on long-term treatment
      rates and patient compliance. The improved use of cardiovascular protective
      therapies was associated with a significant reduction in clinical events the
      first year after discharge: the death and nonfatal myocardial infarction rate
      decreased from 14.8% to 6.4% (odds ratio, 0.43; 95% confidence interval, 0.27
      0.59; P < 0.01). These improved treatment rates have been sustained over an 8
      year period. Compared with conventional care, the Cardiovascular Hospitalization
      Atherosclerosis Management Program has been associated with a significant
      increase in treatment utilization of evidence-based medications, more patients
      achieving low-density lipoprotein cholesterol less than 100 mg/dL, and improved
      clinical outcomes in patients hospitalized for cardiovascular disease. Hospital
      based atherosclerosis treatment systems are an important step to help eliminate
      the cardiovascular treatment gap and dramatically reduce the death and disability
      caused by atherosclerotic vascular disease.

PMID- 18340323
TI  - Acute coronary syndrome emergency treatment strategies: a rationale and road map
      for critical pathway implementation.
AB  - Clinical guidelines have been established to improve the effectiveness of
      treatment of patients seeking treatment for acute coronary syndromes and to
      address the variability in physician approaches to these risks. In patients with
      established coronary heart disease, clinical trials have consistently
      demonstrated reduction in morbidity and mortality with secondary prevention
      therapies. Both ends of this spectrum of therapy can be underused in patients
      receiving conventional care. Because implementation of evidence-based guideline
      recommendations into clinical care is limited, presented here is a rationale and
      process that have been successful in guideline implementation for patients with
      acute coronary syndromes.

PMID- 18340324
TI  - Critical pathway for an aggressive diagnostic strategy for patients who present
      with chest pain but a nondiagnostic electrocardiogram to the emergency
      department.
AB  - BACKGROUND: The prolonged length of stay for patients who seek treatment in the
      emergency department with chest pain and normal or nondiagnostic
      electrocardiogram has led to a backlog of patients in the emergency department
      and the telemetry unit. Correct early management requires risk stratification
      processes that can effectively separate the majority of these patients into low
      risk, low/intermediate-risk, intermediate-risk, and high-risk subsets. METHODS
      AND RESULTS: Patients who seek treatment in the emergency department with chest
      pain are risk-stratified into low-risk, low/intermediate-risk, and high-risk
      categories using a Risk Score to determine who would benefit from immediate
      exercise stress testing. Nurse-directed exercise stress testing using the Duke
      Treadmill Score is used to risk-stratify intermediate-risk patients further "on
      the-fly". Intermediate-risk Duke Treadmill Score patients are injected during
      exercise with a Tc-myocardial perfusion agent and undergo a gated single-photon
      emission computed tomography study. Normal exercise and single-photon emission
      computed tomography perfusion patients are discharged home. The overall length of
      stay and 30-day outcomes of these facilitated patients were compared with those
      of patients treated with a conservative approach using sequential
      electrocardiograms and cardiac enzymes. Patients who were evaluated using the
      facilitated approach had a shorter mean length of stay than those using a
      conservative method, with similar outcomes at 30 days. CONCLUSIONS: A facilitated
      approach incorporating on-demand nurse-directed early exercise stress testing
      with the injection of a Tc-myocardial perfusion agent on the fly in intermediate
      risk patients is safe and has decreased the backlog of patients in the emergency
      department and telemetry unit and expedited appropriate treatment of patients
      with acute chest pain and nondiagnostic electrocardiograms.

PMID- 18340325
TI  - Comment on "Critical pathway for an aggressive diagnostic strategy for patients
      who present with chest pain, but non-diagnostic EKG to the emergency department".

PMID- 18340326
TI  - Periprocedural management of the chronically anticoagulated patient: critical
      pathways for bridging therapy.
AB  - Periprocedural bridging of the patient on long-term anticoagulation is indicated
      in nonvalvular atrial fibrillation with additional risk factors, prosthetic heart
      valves, venous thromboembolism within 3 months of the procedure, and
      hypercoagulable conditions requiring oral anticoagulation. Until recently,
      intravenous unfractionated heparin was used for bridging. LMWH has now emerged as
      a safe and effective bridging alternative.

PMID- 18340327
TI  - Value of the history in evaluating patients for early myocardial ischemia in
      observation chest pain centers.

PMID- 18340328
TI  - Design of a comprehensive chest pain initiative in an academic urban hospital.
AB  - We describe the development and institution of an initiative based on a clinical
      diagnostic algorithm and treatment pathways, facilitated by cardiac nurse
      practitioners, for the treatment of the diverse group of patients with chest pain
      who seek treatment at our urban-based institution. We believe that our chest pain
      initiative incorporates previous strategies of rapid emergency department
      management with inpatient-based care while providing a framework for outpatient
      follow-up and secondary prevention. These strategies allow our hospital to meet
      its goals of providing chest pain patients with standardized, high-quality, and
      expeditious care, given the challenges faced by an academic urban hospital.

PMID- 18340329
TI  - Early warning signs of heart attack: three decades of public and professional
      education in the Southwest Missouri Ozarks.

PMID- 18340330
TI  - Complicated myocardial infarction.

PMID- 18340331
TI  - Use of colorectal cancer tests--United States, 2002, 2004, and 2006.
AB  - Colorectal cancer is the second-leading cause of cancer-related deaths in the
      United States among cancers that affect both men and women. The U.S. Preventive
      Task Force and other national organizations recommend that persons aged > or =50
      years at average risk be screened for colorectal cancer using one or more of the
      following methods: fecal occult blood testing (FOBT) every year, sigmoidoscopy or
      double-contrast barium enema every 5 years, or colonoscopy every 10 years. To
      estimate rates of use of colorectal cancer tests and to evaluate changes in test
      use, CDC compared data from the 2002, 2004, and 2006 Behavioral Risk Factor
      Surveillance System (BRFSS) surveys. This report describes the results of that
      comparison, which indicated that the proportion of respondents aged > or =50
      years reporting use of FOBT and/or sigmoidoscopy or colonoscopy increased overall
      from 2002 to 2006; however, certain populations, such as racial/ethnic minorities
      and those who reported no health insurance coverage, had lower prevalence of
      testing. Specific measures to increase colorectal cancer screening and address
      disparities in screening are needed.

PMID- 18340332
TI  - Update: recommendations from the Advisory Committee on Immunization Practices
      (ACIP) regarding administration of combination MMRV vaccine.
AB  - On February 27, 2008, new information was presented to the Advisory Committee on
      Immunization Practices (ACIP) regarding the risk for febrile seizures among
      children aged 12-23 months after administration of the combination measles,
      mumps, rubella, and varicella (MMRV) vaccine (ProQuad, Merck & Co., Inc.,
      Whitehouse Station, New Jersey). This report summarizes current knowledge
      regarding the risk for febrile seizures after MMRV vaccination and presents
      updated ACIP recommendations that were issued after presentation of the new
      information. These updated recommendations remove ACIP's previous preference for
      administering combination MMRV vaccine over separate injections of equivalent
      component vaccines (i.e., measles, mumps, and rubella [MMR] vaccine and varicella
      vaccine).

PMID- 18340333
TI  - Nonoccupational logging fatalities--Vermont, 1997-2007.
AB  - Professional logging is one of the most hazardous occupations in the United
      States, and the factors contributing to injuries and fatalities associated with
      this occupation are well documented. However, little has been reported about
      logging fatalities in the nonoccupational setting. To better characterize
      nonoccupational logging fatalities, the Vermont Department of Health analyzed
      medical examiner data from Vermont for the period 1997-2007. This report
      describes four cases and summarizes data on all nonoccupational logging
      fatalities. The findings indicated that tree felling accounted for 15 (83%) of
      the 18 nonoccupational logging fatalities during the 11-year period and that 14
      (78%) of the fatalities were attributed to injuries resulting from being struck
      by a falling tree or limb. Contributing factors in these incidents included
      absence of personal protective equipment (PPE), misjudgment of the path of
      falling trees, and being alone. Measures to reduce nonoccupational logging
      fatalities should focus on promoting safe tree-felling practices and increasing
      helmet use among nonprofessional woodcutters. Ideally, however, nonprofessionals
      should not participate in tree felling.

PMID- 18340334
TI  - Progress toward measles mortality reduction and elimination--Eastern
      Mediterranean Region, 1997-2007.
AB  - In 2005, the World Health Assembly set a goal of achieving a 90% reduction in
      global measles mortality by 2010, compared with levels in 2000. Eight years
      earlier, in 1997, the 22 countries in the World Health Organization (WHO) Eastern
      Mediterranean Region (EMR) had resolved to eliminate measles from their region by
      2010. To reach these two goals, the WHO Regional Office for the Eastern
      Mediterranean developed a four-pronged strategy: 1) achieve and maintain > or
      =90% vaccination coverage of children with the first dose of measles-containing
      vaccine (MCV1) in every district of each country through routine immunization
      services, 2) achieve > or =90% vaccination coverage with the second dose of
      measles-containing vaccine (MCV2) in every district either through a routine 2
      dose vaccination schedule or through supplementary immunization activities
      (SIAs), 3) establish case-based surveillance with investigation and laboratory
      testing of all suspected cases of measles, and 4) provide optimal clinical-case
      management, including supplementation of diets with vitamin A. This report
      summarizes the progress made in the EMR during 1997-2007 toward reducing
      mortality from measles and eliminating measles from the region. Countries in the
      EMR reduced the number of measles-related deaths by approximately 75% from 2000
      to 2007. However, large measles outbreaks continue to occur throughout the
      region, suggesting that much work remains to eliminate measles in the EMR.

PMID- 18340336
TI  - Oral health-related quality of life and the IOTN index as predictors of
      children's perceived needs and acceptance for orthodontic treatment.
AB  - OBJECTIVE: To evaluate whether the index of orthodontic treatment need (IOTN)
      could be improved by adding an oral health-related quality of life measure to
      predict both the outcome of orthodontic consultation and the child's perceived
      need for orthodontic treatment. METHODS: The sample consisted of 187 children
      aged 11-16 years referred to orthodontic clinics in the Bedfordshire Personal
      Dental Service (PDS) in the United Kingdom. The children completed a
      questionnaire containing the Child Perception Questionnaire (CPQ11-14), were
      clinically examined and completed the Child-OIDP index in face-to-face
      interviews. Demographic information and perceived need for orthodontic treatment
      were also collected. Clinical data on orthodontic treatment need was collected
      using the IOTN. RESULTS: 49.3% of children reported one or more oral impacts.
      Combining the IOTN index with either of the two oral health-related quality of
      life measures used in this study did not predict outcome of consultation, however
      it explained children's perceived need for braces. There were some discrepancies
      between need according to the orthodontist and children's perceptions.
      CONCLUSIONS: Adding an oral health-related quality of life measure to IOTN did
      not influence prediction of outcome of consultation but it explained the
      prediction of perceived need for braces. Importantly, children with an impact
      were denied orthodontic treatment.

PMID- 18340335
TI  - Improved group-specific PCR primers for denaturing gradient gel electrophoresis
      analysis of the genetic diversity of complex microbial communities.
AB  - Phylum- and class-specific PCR primers were tested for the production of clone
      libraries and for denaturing gradient gel electrophoresis (DGGE) analysis of
      complex bacterial communities. Primers were designed to specifically amplify 16S
      rRNA gene fragments of the phyla Bacteroidetes, Planctomycetes and Firmicutes, of
      three classes of the phylum Proteobacteria, the Alphaproteobacteria,
      Betaproteobacteria and Gammaproteobacteria, and of the Cyanobacteria (including
      chloroplast 16S rRNA genes). The specificity of the seven primer pairs was tested
      by producing clone libraries from environmental DNA samples from mesotrophic
      (Norwegian coastal) and oligotrophic (Northern Atlantic Gyre) environments. Five
      of the seven primer pairs specifically amplified target 16S rRNA gene sequences.
      Exceptions were the Betaproteobacteria- and Firmicutes-specific primers, which
      were relatively successful with coastal water mesocosm samples but less so with
      the Northern Atlantic Gyre sample. Phylogenetic analysis of sequences from the
      Gammaproteobacteria clone library revealed that the coastal sample yielded a
      number of clones that clustered within clades that belong to the oligotrophic
      marine Gammaproteobacteria (OMG) group, indicating that this group is not
      confined exclusively to the oligotrophic environment. Comparison of the bacterial
      diversity of the environmental DNA sample from the coastal and the open ocean
      using a two- or three-step nested PCR-DGGE process revealed significant
      differences in the bacterial communities. The application of the group-specific
      primers provides a higher resolution genetic fingerprinting approach than
      existing DGGE primer sets.

PMID- 18340337
TI  - IID2008. Abstracts of the 2008 International Investigative Dermatology Meeting.

PMID- 18340340
TI  - Aliskiren: the first renin inhibitor for clinical treatment.
AB  - The first evidence of the existence of renin was presented over 100 years ago.
      However, the importance of renin and the renin-angiotensin system in the
      pathogenesis of cardiovascular disease was only fully realized in the 1970s. It
      was another 20 years before the first inhibitors of renin were available for
      clinical research. Here, we describe the discovery and development of aliskiren,
      an orally active renin inhibitor, which became the first drug in its class to
      receive regulatory approval. In 2007, it was approved for the treatment of
      hypertension by the US Food and Drug Administration and the European Medicines
      Agency.

PMID- 18340341
TI  - The role of Streptococcus pneumoniae virulence factors in host respiratory
      colonization and disease.
AB  - Streptococcus pneumoniae is a Gram-positive bacterial pathogen that colonizes the
      mucosal surfaces of the host nasopharynx and upper airway. Through a combination
      of virulence-factor activity and an ability to evade the early components of the
      host immune response, this organism can spread from the upper respiratory tract
      to the sterile regions of the lower respiratory tract, which leads to pneumonia.
      In this Review, we describe how S. pneumoniae uses its armamentarium of virulence
      factors to colonize the upper and lower respiratory tracts of the host and cause
      disease.

PMID- 18340342
TI  - Anammox bacteria: from discovery to application.
AB  - Anaerobic ammonium oxidation (anammox) bacteria, which were discovered in waste
      water sludge in the early 1990s, have the unique metabolic ability to combine
      ammonium and nitrite or nitrate to form nitrogen gas. This discovery led to the
      realization that a substantial part of the enormous nitrogen losses that are
      observed in the marine environment--up to 50% of the total nitrogen turnover-
      were due to the activity of these bacteria. In this Timeline, Gijs Kuenen recalls
      the discovery of these unique microorganisms and describes the continuing
      elucidation of their roles in environmental and industrial microbiology.

PMID- 18340343
TI  - DNA polymerases in adaptive immunity.
AB  - To cope with an unpredictable variety of potential pathogenic insults, the immune
      system must generate an enormous diversity of recognition structures, and it does
      so by making stepwise modifications at key genetic loci in each lymphoid cell.
      These modifications proceed through the action of lymphoid-specific proteins
      acting together with the general DNA-repair machinery of the cell. Strikingly,
      these general mechanisms are usually diverted from their normal functions, being
      used in rather atypical ways in order to privilege diversity over accuracy. In
      this Review, we focus on the contribution of a set of DNA polymerases discovered
      in the past decade to these unique DNA transactions.

PMID- 18340344
TI  - Evolutionary struggles between NK cells and viruses.
AB  - Natural killer (NK) cells are well recognized for their ability to provide a
      first line of defence against viral pathogens and they are increasingly being
      implicated in immune responses against certain bacterial and parasitic
      infections. Reciprocally, viruses have devised numerous strategies to evade the
      activation of NK cells and have influenced the evolution of NK-cell receptors and
      their ligands. NK cells contribute to host defence by their ability to rapidly
      secrete cytokines and chemokines, as well as to directly kill infected host
      cells. In addition to their participation in the immediate innate immune response
      against infection, interactions between NK cells and dendritic cells shape the
      nature of the subsequent adaptive immune response to pathogens.

PMID- 18340346
TI  - The SCF FSN-1 ubiquitin ligase controls germline apoptosis through CEP-1/p53 in
      C. elegans.
AB  - The nematode Caenorhabditis elegans contains a single ancestral p53 family
      member, cep-1, which is required to activate apoptosis of germ cells in response
      to DNA damage. To understand how the cep-1/p53 pathway is regulated in response
      to genotoxic stress, we performed an RNA interference screen and identified the
      neddylation pathway and components of an SCF (Skp1/cullin/F-box) E3 ubiquitin
      ligase as negative regulators of cep-1-dependent germ cell apoptosis. Here, we
      show that the cullin gene cul-1, the Skp1-related gene skr-1, and the ring box
      genes rbx-1 and rpm-1 all negatively regulate cep-1-dependent germ cell apoptosis
      in response to the DNA-alkylating agent N-ethyl-N-nitrosourea (ENU). We also
      identified the F-box protein FSN-1, previously shown to form an SCF ligase that
      regulates synapse development, as a negative regulator of cep-1-dependent
      germline apoptosis. The hypersensitivity of fsn-1 mutants to ENU-induced germline
      apoptosis was completely suppressed by a cep-1 loss-of-function allele. We
      further provide evidence that the transcriptional activity, phosphorylation
      status, and levels of endogenous CEP-1 are higher in fsn-1 mutants compared with
      wild-type animals after ENU treatment. Our results uncover a novel role for the
      SCF(FSN-1) E3 ubiquitin ligase in the regulation of cep-1-dependent germ cell
      apoptosis.

PMID- 18340345
TI  - How dying cells alert the immune system to danger.
AB  - When a cell dies in vivo, the event does not go unnoticed. The host has evolved
      mechanisms to detect the death of cells and rapidly investigate the nature of
      their demise. If cell death is a result of natural causes - that is, it is part
      of normal physiological processes - then there is little threat to the organism.
      In this situation, little else is done other than to remove the corpse. However,
      if cells have died as the consequence of some violence or disease, then both
      defence and repair mechanisms are mobilized in the host. The importance of these
      processes to host defence and disease pathogenesis has only been appreciated
      relatively recently. This article reviews our current knowledge of these
      processes.

PMID- 18340348
TI  - Women in medicine: achieving tenure at home and work--prioritization is a
      personal decision.

PMID- 18340349
TI  - Calcium antagonists: Do they equally protect against kidney injury?
AB  - Calcium antagonists are a heterogeneous group of drugs that affect not only
      different channels but different parts of the same channel. These differences
      translate into different renal hemodynamic effects. This Commentary discusses the
      implications of these differences for surrogate markers of outcome.

PMID- 18340350
TI  - Low oxygen stimulates the immune system.
AB  - Changes in tissue oxygen levels trigger molecular signaling pathways that
      regulate cellular proliferation and differentiation in multiple cell types. The
      functional role of oxygen signaling in the immune system is not well understood.
      Rama and colleagues demonstrate that hypoxia induces dendritic-cell maturation;
      thus they provide a novel mechanistic link between hypoxia/ischemia and the
      activation of the immune system in the kidney.

PMID- 18340351
TI  - Hepatitis B in chronic kidney disease: moving toward effective prevention.
AB  - Control of hepatitis B virus (HBV) infection has been a continuous challenge in
      the management of patients with advanced kidney disease. HBV infections are still
      difficult to treat, so the main objective is disease prevention by timely
      immunization with hepatitis B surface antigen vaccines. In the general
      population, a simple two- or three-standard-dose vaccination strategy has been
      proven to be highly successful. In contrast, an intensified and more tailored
      approach is evolving in patients with advanced renal failure.

PMID- 18340352
TI  - Acute kidney injury: Better biomarkers and beyond.
AB  - We review fundamental epidemiologic concepts for testing the new early acute
      kidney injury biomarkers in clinical care.

PMID- 18340354
TI  - The case / Acute renal failure and anemia.

PMID- 18340355
TI  - A permanent tan from iron.

PMID- 18340356
TI  - Silencing Livin gene expression to inhibit proliferation and enhance
      chemosensitivity in tumor cells.
AB  - Livin, a novel member of the human inhibitors of apoptosis protein (IAP) family,
      plays an important role in tumor progression and occurrence by inhibiting cell
      apoptosis. It is selectively expressed in the most common human neoplasms and
      appears to be involved in tumor cell resistance to chemotherapeutic agents. To
      investigate its possibility as a therapeutic target for human malignancies, we
      established two genetically different stable tumor cell lines (LoVo and SPCA-1)
      and RNA interference (RNAi) technique was employed to downregulate Livin
      expression in two human tumor cell lines. The specific downregulation of Livin
      expression in tumor cell lines significantly inhibited in vitro cell
      proliferation and in vivo tumorigenicity. Furthermore, Livin knockdown led to
      cell arrest in the G(1)/G(0) phase of cell cycle, eventual apoptosis and
      chemosensitivity enhancement in tumor cells. All these results indicate that RNAi
      mediated downregulation of Livin expression can lead to potent antitumor activity
      and chemosensitizing effects in human cancers.

PMID- 18340357
TI  - In vivo restoration of RhoB expression leads to ovarian tumor regression.
AB  - Ovarian cancers are very aggressive cancers most often diagnosed when metastasis
      has already occurred in the entire peritoneal cavity. Ovarian adenocarcinoma
      cells present an undetectable level of RhoB GTPase. Using preclinical ovarian
      cancer models, we aimed to evaluate the potential use of RhoB cDNA as a tumor
      suppressor gene in gene therapy. RhoB restoration in vitro, through recombinant
      adenovirus transduction, resulted in the apoptosis of endogenous RhoB protein low
      expressing cell lines (OVCAR-3 and IGROV-1) through the activation of the
      intrinsic apoptotic caspase cascade. We showed that a single injection of 10(8)
      p.f.u. of adenoviral vector encoding a reporter gene into the peritoneal cavity
      of ovarian tumor bearing mice can induce the gene modification of a large
      quantity of cells throughout the cavity. We thereby tested the effect of AdRhoB
      injections to treat ovarian cancer-bearing mice. The ectopic expression of RhoB,
      following its introduction via viral transduction into nude mice in vivo, was
      highly effective in suppressing tumor growth of ovarian cancer xenografts.
      Therapeutic agents designed to correct defects of RhoB at the molecular level may
      thereby provide innovative treatment options for patients not responding to
      standard therapies.

PMID- 18340358
TI  - The effect of NOD2 activation on TLR2-mediated cytokine responses is dependent on
      activation dose and NOD2 genotype.
AB  - The mechanism by which mutations in NOD2 predispose to Crohn's disease (CD) is
      incompletely understood. In mice, NOD2 has been found to function as a negative
      regulator of Toll-like receptor 2 (TLR2) signaling. In contrast, studies in
      humans so far showed no negative regulatory interaction between NOD2 and TLR2,
      and in fact suggest a synergistic effect between the two. Here, we show that this
      interaction is dose dependent. Adding low doses of muramyl dipeptide (MDP) to
      TLR2 primed monocytes results in a significant increase in cytokine production,
      whereas adding higher doses of MDP led to a striking downregulation of the
      responses. This downregulation by high-dose MDP does not occur in monocytes from
      NOD2-deficient patients. The inhibitory role of NOD2 at high concentrations of
      MDP implicates a safety mechanism to prevent exaggerated antibacterial immune
      responses in the gut to high or perpetuating bacterial load. This regulatory
      mechanism is lost in NOD2-deficient CD patients.

PMID- 18340359
TI  - Lack of association between genetic variation in G-protein-coupled receptor for
      asthma susceptibility and childhood asthma and atopy.
AB  - G-protein-coupled receptor for asthma susceptibility (GPRA or GPR154) was
      identified as an asthma and atopy candidate gene by positional cloning. Some
      subsequent studies suggest associations of GPRA single nucleotide polymorphisms
      (SNPs) and haplotypes with asthma or atopy susceptibility. However, the
      associated SNPs or haplotypes vary among studies. The role of GPRA genetic
      variation in asthma and atopy remains unsolved. Published data on GRPA variants
      and asthma come exclusively from Caucasian and Asian populations. We examined
      whether GPRA SNPs and haplotypes are associated with asthma and atopy in a
      Mexican population. We genotyped and analyzed 27 GPRA SNPs in 589 nuclear
      families consisting of asthmatic children aged 4-17 years of age and their
      parents in Mexico City. Atopy was determined by skin prick tests to 25
      aeroallergens. The 27 SNPs examined provided excellent coverage of the GPRA gene.
      GPRA SNPs and haplotypes were not associated with childhood asthma and the degree
      of atopy to aeroallergens in a Mexican population. Our review of studies of GPRA
      variants in relation to asthma phenotypes shows considerable heterogeneity.
      Accordingly, our results suggest that GPRA variants are not an important
      contributor to childhood asthma and atopy susceptibility in a Mexican population.

PMID- 18340360
TI  - Combination of KIR and HLA gene variants augments the risk of developing birdshot
      chorioretinopathy in HLA-A*29-positive individuals.
AB  - Birdshot chorioretinopathy (BCR), a chronic ocular inflammatory disease with
      characteristic choroidal lymphocytic infiltrates, has been strongly associated
      with human leukocyte antigen (HLA)-A29. Although HLA-A29 occurs frequently in all
      populations, BCR affects only a small percentage of HLA-A29-positive Caucasians,
      indicating additional susceptibility factors for BCR. Discovery of HLA class I
      specific killer cell immunoglobulin-like receptors (KIR) led to a series of
      epidemiological studies implicating KIR-HLA gene combinations in disease. Here,
      we characterized KIR-HLA pairs in BCR patients and controls carrying HLA-A*29 as
      well as controls lacking HLA-A*29. KIR-HLA pairs implicated for weak inhibition
      (KIR2DL2/3+HLA-C1 and KIR3DL1+HLA-Bw4(T80)) in combination with activating KIR
      genes associated with autoimmunity (KIR2DS2, 2DS3 and 2DS4) augment the risk of
      developing BCR in HLA-A*29-positive individuals. The reciprocal association of
      strong inhibitory pairs (KIR3DL1+HLA-Bw4(I80) and KIR2DL1+HLA-C2) in combination
      with those implicated in protection from infection (KIR3DS1+HLA-Bw4(I80) and
      KIR2DS1+HLA-C2) was observed in HLA-A*29-negative controls. These results suggest
      that a profound effect of KIR2DS2/S3/S4 in the absence of strong inhibition may
      enhance the activation of natural killer cells and T-cell subsets against
      intraocular self-antigens, thereby contributing to pathogenesis of BCR.

PMID- 18340361
TI  - The association between type 1 diabetes and the ITPR3 gene polymorphism due to
      linkage disequilibrium with HLA class II.
AB  - A fine mapping study of the MHC region in a Swedish case-control population
      sample reported a novel type 1 diabetes (T1D) association from the inositol 1-, 4
      , 5-trisphosphate receptor type 3 gene (ITPR3) in a case-control study,
      reportedly independent of the HLA class II effect. We attempted to replicate this
      novel association in a family-based study of 1120 T1D families with at least one
      affected child, an approach immune to population stratification. We found
      association of the ITPR3 single nucleotide polymorphisms (SNPs) rs2296336 with
      T1D but in a direction opposite to that reported. Moreover, rs2296336 was in
      linkage disequilibrium (LD) with specific alleles of the HLA DQB1 gene.
      Conditional regression showed that all of the ITPR3 SNP T1D association could be
      accounted for by the DQB1 effect. Therefore, our findings do not support an
      obvious role of genetic variation of the ITPR3 gene in T1D risk.

PMID- 18340362
TI  - From model cell line to in vivo gene expression: disease-related intestinal gene
      expression in IBD.
AB  - Crohn's disease (CD) and ulcerative colitis (UC) are subforms of inflammatory
      bowel diseases (IBD). Genetic and environmental factors influencing the onset and
      course of the diseases have been recently identified. This study uses a two-step
      approach to detect genes involved in the pathogenesis of IBD by microarray
      analysis and real-time PCR (RT-PCR). In a first step, microarray expression
      screening was used to obtain tumour necrosis factor-alpha (TNF-alpha) induction
      profiles of two human cell lines to represent the tissue cell types involved in
      IBD. In a second step, a subset of differentially expressed genes was examined by
      real-time PCR in intestinal biopsy samples of normal controls (NC) compared with
      UC and CD patients, as well as to a cohort of patients suffering from intestinal
      diseases other than IBD. Data were obtained from 88 CD, 88 UC, 53 non-IBD
      patients (inflammatory control), DC and 45 NC individuals. The experimental
      design enabled the identification of disease-specific expressed genes. DnaJ
      (Hsp40) homologue, subfamily B, member 5 (DNAJB5) was downregulated in intestinal
      biopsy samples of the UC cohort compared with NC. A difference in JUNB expression
      levels was observed by comparing biopsy samples from inflamed and non-inflamed
      areas of UC patients. Transcript expression differences between IBD and control
      cohorts were found by examining histamine N-methyltransferase (HNMT), interleukin
      1A (IL-1A) and proplatelet basic protein (PPBP) expression. The experimental
      procedure represents an approach to identify disease-relevant genes, which is
      applicable to any disease where appropriate model systems are available.

PMID- 18340363
TI  - Complement factor H polymorphisms, renal phenotypes and age-related macular
      degeneration: the Blue Mountains Eye Study.
AB  - Complement factor H (CFH) is a key regulator of the alternative pathway of
      complement and its mutations have been associated with membranoproliferative
      glomerulonephritis type II, atypical hemolytic uremic syndrome and age-related
      macular degeneration (AMD), suggesting that alternative pathway dysregulation is
      a common pathogenetic feature of these ocular and renal conditions. In this study
      we tested the hypothesis that common CFH variants have a global role in renal
      function in the Australian population-based Blue Mountains Eye Study (BMES). We
      replicated the association of I62V with estimated glomerular filtration rate
      (GFR; P=0.017) and creatinine clearance (CRCL; P=0.015). The minor allele of I62V
      (G) was deleterious: adding one copy of the G allele decreased GFR/CRCL by
      approximately 0.98 ml min(-1) per 1.73 m(2) (95% confidence interval (CI): 0.97,
      0.99). We also replicated the association of Y402H with AMD and provided an
      unbiased estimate of population attributable risk (PAR). The minor allele of
      Y402H (C) was deleterious: the odds ratio estimate of CC genotype compared to TT
      was 1.87 (95% CI: 1.44, 2.45). The PAR of the C allele was estimated as 0.22 (95%
      CI: 0.15, 0.28). In summary, in the BMES population we confirmed the association
      between I62V and renal function, as measured by the estimated GFR, plus the
      association of Y402H with both early- and late-stage AMD.

PMID- 18340364
TI  - The vulnerable newborn: time we pay attention to them !

PMID- 18340365
TI  - Colonic diverticular disease: current perspectives.
AB  - Diverticular disease is a common condition affecting large intestine in the
      western world, which, although remains asymptomatic in majority of people, can
      present with abdominal pain, acute diverticulitis, perforation, haemorrhage,
      intestinal obstruction and fistulation through neighbouring organs. Complicated
      colonic diverticular disease (CDD) is associated with significant morbidity and
      mortality. Increasing urbanisation globally with intake of diet deficient in
      fibres has led to CDD as a significant problem; hence awareness of CDD is
      paramount for its prevention and appropriate management. The purpose of this
      article is to provide a comprehensive review of the epidemiology,
      pathophysiology, clinical presentations, and current management of diverticular
      disease of the colon and its complications.

PMID- 18340366
TI  - Comparative study between tramadol and dexamethasone as an admixture to
      bupivacaine in supraclavicular brachial plexus block.
AB  - This is a prospective, randomized, double blind study to evaluate the
      postoperative analgesia following supraclavicular brachial plexus block with
      Tramadol or Dexamethasone as an admixture to bupivacaine in upper extremity
      surgery. Total 60 patients of ASA I and II undergoing upper extremity surgery
      under brachial plexus block with Bupivacaine were randomly divided in to two
      groups; one group received Tramadol (2 mg/kg) and the other group received
      Dexamethasone (8 mg) as an admixture to Bupivacaine. The duration of
      postoperative analgesia was recorded in both groups using pain VAS score which
      was determined by maximum VAS score of 8-10 and when patient demands for
      additional analgesics. The mean duration of postoperative analgesia in the
      Dexamethasone group was 1028.00 minutes while in the tramadol group it was 453.17
      minutes We concluded that Dexamethasone with local anaesthetic prolongs
      postoperative analgesia significantly than Tramadol (P<0.05) when used as
      admixture to local anaesthetic in brachial plexus block in upper extremity
      surgery.

PMID- 18340367
TI  - Abnormal hepatic function and splenomegaly on the newly diagnosed acute leukemia
      patients.
AB  - To evaluate the liver function, splenomegaly and related factors in the newly
      diagnosed acute leukemia patients. One hundred of fifty eight acute leukemia
      patients admitted in our hospital from March 2003 to April 2006 were studied. The
      related factors such as peripheral WBC count, bone marrow blasts, peripheral
      blasts, sex, age, AML, ALL affecting the liver function and splenomegaly were
      evaluated. Sixty two (39.24%) patients presented with splenomegaly. Twelve
      (7.59%) patients presented with hepatomegaly. Serum ALT was elevated in 54
      (34.17%) patients. Similarly, serum AST, GGT, ALP, and Direct bilirubin were
      elevated in 26 (16.45%), 32 (20.25%), 20 (12.65%), and 22 (13.92%) patients,
      respectively. Low serum albumin was found in 40 (25.31%) patients. PT was
      prolonged in 62 (39.24%) patients. Statistical study shows that there is a
      relation between high WBC counts and elevated serum ALT (P<0.05) and high WBC
      counts and splenomegaly (P<0.05). Acute leukemia patients with leukocytosis are
      more prone to develop abnormal liver function and splenomegaly.

PMID- 18340368
TI  - Surgical treatment of isthmic spondylolisthesis with radicular pain in adults.
AB  - A common consensus has not yet been reached on surgical management of isthmic
      Spondylolisthesis especially regarding the optimal surgical procedure. This
      prospective study was carried to see the outcome of Posterolateral fusion with
      instrumentation without decompression. Eight consecutive patients, aged between
      43 to 55 years, underwent primary surgery for isolated L4, L5 lumbar isthmic
      Spondylolisthesis of less than grade II that presented with radicular pain and
      exhibited instability on dynamic radiograph. The surgical procedure consisted of
      instrumentation with pedicle screws and rods (Moss Miami System) and
      posterolateral fusion in situ by placement of autogeneous bone graft, harvested
      from posterior iliac crest. Postoperatively Clinical and Radiological status were
      assessed and were graded according to Stauffer and Coventry method. The patients
      were followed up for one to three years. Radiological evidence of fusion was
      clearly evident by six months in all cases. Symptomatically all were relieved of
      radicular pain completely. One patient had recurrent backache due to causes
      unrelated to the illness of surgical procedure requiring occasional analgesic. No
      serious complication was encountered. This lead to conclusion that in adults of
      our population with low grade isthmic spondylolisthesis and radicular pain
      Instrumentation with Posterolateral fusion without decompression was sufficient
      to relieve symptoms.

PMID- 18340369
TI  - Prevalence of acute diarrhoea in Kathmandu valley.
AB  - This retrospective study was conducted during January to September in the year
      1997. Three hundred and forty nine stool samples were collected from diarrhoea
      patients from different places of Kathmandu valley and examined at National
      Public Health Laboratory (NPHL), Teku, Kathmandu. Acute diarrhoea becomes
      epidemic in rainy season and is a major public health problem of the city. In
      this study, people with poor hygiene practice and poor education were infected
      more than other people. Among the 349 patients with the gastrointestinal disease,
      26.0% were found to have bacterial infection. Out of which, 88 (25.1%), one
      (0.28%), one (0.28%), and one (0.28%) were found to be Vibrio cholerae 01, Vibrio
      cholerae 0139, Shigella dysenteriae and Escherichia coli respectively. Cholera
      cases were found almost throughout the year in the city though the numbers
      increased during the rainy season. It was highest during July (34.6%) followed by
      August (32.35%), September 32% and June (6.89%). The uncommon species of Vibrio
      i.e. Vibrio cholerae 0139 was also found in the study. Higher prevalence was
      found in urban areas (83.52%) than in rural areas (16.48%). Antimicrobial
      susceptibility testing of bacterial isolates showed that Ciprofloxacin (97.85%)
      was found to be the most effective antibiotic followed by Tetracycline (92.34%),
      Erythromycin (92.34%), Norfloxacin (93.34%), Cholramphenicol, Ampicillim, but
      Cotrimoxazole were found to be resistant to all isolated Vibrio cholerae.

PMID- 18340370
TI  - Frequency dependence of hearing loss with perforations.
AB  - This cross-sectional study was conducted in different sizes of pars tensa
      perforation in patients with chronic suppurative otitis media (CSOM) tubo
      tympanic type undergoing myringoplasty. A total of 50 patients were recruited
      from the outpatient Department of Otorhinolaryngology - Head and Neck Surgery in
      TU Teaching Hospital from June 2003 to May 2004. Cases of CSOM tubo-tympanic type
      with dry central perforation, conductive type of hearing loss were subjected to
      myringoplasty. Preoperative audiometric evaluations were done. While operating
      under microscope diameter of perforations were measured and perforations were
      grouped according to the size. This study showed that the hearing loss was found
      to be more at lower frequencies and less as the frequencies increased. Hearing
      loss is more marked at lower frequencies as compared to higher frequencies,
      irrespective any size or location of perforation of pars tensa.

PMID- 18340371
TI  - A study of Body Mass Index (BMI) of Nepalese women attending gynaecology clinic.
AB  - This prospective study was carried out to find out the body mass index (BMI) of
      all the women attending a gynaecological clinic at Kathmandu Valley. Total of
      1450 women attended this clinic over the study period. After excluding few
      hundreds of women, one thousand women of reproductive age (15-49) were enrolled.
      Detail history was taken, general, systemic and pelvic examinations were
      performed and a provisional diagnosis was made on the clinical ground. In this
      process height and weight of each patient was measured then Body Mass Index (BMI)
      was calculated. Eight percent (8%) of women were underweight and equal numbers of
      them were obese too. Forty-four point six percent were healthy and 37.3 were
      overweight. Most of them were diagnosed vaginitis, urinary tract infection (UTI),
      pelvic inflammatory disease (PID), subfertility, menstrual disorders, and
      cervical conditions. In eleven percent no gynaecological abnormalities were
      detected (NAD). Commonly diagnosed conditions were vaginitis, UTI, PID, primary
      subfertility and menstrual disorders were the commonly diagnosed conditions.

PMID- 18340372
TI  - Treatment of recurrent anterior dislocations of shoulder by Laterjet-Bristow
      operation: an experience.
AB  - Shoulder dislocation is common problem in orthopaedics. Management of recurrent
      shoulder dislocation is painstaking with different surgical procedures having
      varying outcomes. Laterjet-Bristow procedure provides stability and good
      functional outcome in Rowe scale and long term patient satisfaction. This is an
      observational prospective study carried out at two different tertiary care
      centers at Nepal and Pakistan using the same protocol. Habitual and pathological
      recurrent dislocations were excluded and all the recurrent dislocation of
      shoulder following initial traumatic anterior dislocation was included in this
      study. Standard Laterjet-Bristow operation was done and followed up for average
      of 27 months. Functional evaluation was done using Rowe score and graded as
      excellent, good, fair and poor. There were 12 men and 9 women with the mean ages
      of 23.4 years. At 12 months, 11 patients had fair result and seven patients had
      good result. At two years only three had fair result, 15 had good result and
      three patients had excellent result. Only three patients had poor result at one
      year while none had poor result at two year. The mean loss of external rotation
      in operated shoulder at one year was 24.33 degrees which decreased to 21.2
      degrees at the end of second year. There was no restriction of external rotation
      in three patients at both yearly follow-ups while 18 patients had restriction in
      the range 10-30 degrees. Laterjet-Bristow can be the procedure of choice for
      surgical treatment of recurrent traumatic anterior dislocation and also as a
      salvage surgery for failed cases from other types of procedures. The only
      shortcoming of this procedure was some limitation in external rotation and minor
      loss in muscle power of that shoulder.

PMID- 18340373
TI  - Sarcoidosis--three clinical vignettes with a short review.
AB  - Sarcoidosis is a multi system disorder of unknown cause most commonly affecting
      the young and middle age adults and frequently presents bilateral hilar lymph
      adenopathy. The diagnosis of sarcoidosis is often delayed following the onset of
      symptoms. The reason being first, the disease is often sub clinical; second as
      the disease affects any system, the diagnosis of sarcoidosis may not be
      considered; third, the symptoms are not disease specific hence often treated as
      other chronic pulmonary diseases; finally economic issues or barriers to access
      for further workup may affect the timeliness of the diagnosis. No laboratory
      diagnosis is specific for diagnosing sarcoidosis but histological confirmation
      from the lymph nodes accessible for biopsy either direct or by intervention may
      be more specific.

PMID- 18340374
TI  - Diagnostic dilemma of an unusual pelvic mass in a young girl.
AB  - Dysgerminoma of ovary is the most common germ cell tumor, accounting for 50% of
      all germ cell tumor cases. About 20% of cases are diagnosed during pregnancy, and
      80% occur in women under 30. It is rare to find both ovaries to be involved in
      germ cell tumors. The prognosis of patients with malignant germ cell has improved
      significantly over the last two decades after the introduction of chemotherapy
      specially cisplatin. The only exceptions are stage 1, grade 1, immature teratoma
      and stage 1A dysgerminoima who are followed up after surgery without adjuvant
      chemotherapy. Normal ovarian functions and fertility can be retained in most
      patients by following the conservative surgery.

PMID- 18340375
TI  - Primary malignant melanoma of vagina--a case report with review of literature.
AB  - Primary vaginal malignant melanoma is a very rare tumor with less than 300 cases
      reported to date. We describe a case of primary vaginal melanoma and review the
      literature. A 60 years postmenopausal female patient presented with painless mass
      coming out of the vagina with occasional bleeding for last 2-3 weeks. On vaginal
      examination there was a firm polypoidal growth of size 7 cm attached to the right
      lateral wall of vagina and coming out of the introitus. Histopathology of the
      mass showed features of malignant melanoma. Wide local excision was done and
      adjuvant therapy was given. However patient came back after three months with
      widespread metastasis and expired 6 months after the initial diagnosis. Vaginal
      melanoma is a very aggressive tumor and the overall prognosis is very poor
      despite the treatment modality.

PMID- 18340376
TI  - Motif discovery in tissue-specific regulatory sequences using directed
      information.
AB  - Motif discovery for the identification of functional regulatory elements
      underlying gene expression is a challenging problem. Sequence inspection often
      leads to discovery of novel motifs (including transcription factor sites) with
      previously uncharacterized function in gene expression. Coupled with the
      complexity underlying tissue-specific gene expression, there are several motifs
      that are putatively responsible for expression in a certain cell type. This has
      important implications in understanding fundamental biological processes such as
      development and disease progression. In this work, we present an approach to the
      identification of motifs (not necessarily transcription factor sites) and examine
      its application to some questions in current bioinformatics research. These
      motifs are seen to discriminate tissue-specific gene promoter or regulatory
      regions from those that are not tissue-specific. There are two main contributions
      of this work. Firstly, we propose the use of directed information for such
      classification constrained motif discovery, and then use the selected features
      with a support vector machine (SVM) classifier to find the tissue specificity of
      any sequence of interest. Such analysis yields several novel interesting motifs
      that merit further experimental characterization. Furthermore, this approach
      leads to a principled framework for the prospective examination of any chosen
      motif to be discriminatory motif for a group of coexpressed/coregulated genes,
      thereby integrating sequence and expression perspectives. We hypothesize that the
      discovery of these motifs would enable the large-scale investigation for the
      tissue-specific regulatory role of any conserved sequence element identified from
      genome-wide studies.

PMID- 18340377
TI  - Excess adenosine in murine penile erectile tissues contributes to priapism via
      A2B adenosine receptor signaling.
AB  - Priapism, abnormally prolonged penile erection in the absence of sexual
      excitation, is associated with ischemia-mediated erectile tissue damage and
      subsequent erectile dysfunction. It is common among males with sickle cell
      disease (SCD), and SCD transgenic mice are an accepted model of the disorder.
      Current strategies to manage priapism suffer from a poor fundamental
      understanding of the molecular mechanisms underlying the disorder. Here we report
      that mice lacking adenosine deaminase (ADA), an enzyme necessary for the
      breakdown of adenosine, displayed unexpected priapic activity. ADA enzyme therapy
      successfully corrected the priapic activity both in vivo and in vitro, suggesting
      that it was dependent on elevated adenosine levels. Further genetic and
      pharmacologic evidence demonstrated that A2B adenosine receptor-mediated (A2BR
      mediated) cAMP and cGMP induction was required for elevated adenosine-induced
      prolonged penile erection. Finally, priapic activity in SCD transgenic mice was
      also caused by elevated adenosine levels and A2BR activation. Thus, we have shown
      that excessive adenosine accumulation in the penis contributes to priapism
      through increased A2BR signaling in both Ada -/- and SCD transgenic mice. These
      findings provide insight regarding the molecular basis of priapism and suggest
      that strategies to either reduce adenosine or block A2BR activation may prove
      beneficial in the treatment of this disorder.

PMID- 18340378
TI  - The initial steps of ovarian cancer cell metastasis are mediated by MMP-2
      cleavage of vitronectin and fibronectin.
AB  - Most patients (80%) with ovarian cancer (OvCa) present with metastatic disease.
      Attachment of OvCa cells to peritoneum and omentum represents the first rate
      limiting step for metastatic spread. Therefore, identifying factors regulating
      cell attachment in the abdominal cavity is critical to the development of
      therapeutic agents. We show here that MMP-2 expression was upregulated in OvCa
      cells upon attachment to their microenvironment. Downregulation of MMP-2 mRNA or
      pharmacological inhibition of MMP-2 proteolytic function, in both human OvCa
      primary cells and cell lines, reduced attachment of OvCa cells to a 3D
      organotypic model of metastatic OvCa, full human omentum or peritoneum, and in
      vivo to mouse peritoneum and omentum. Absence of MMP-2 in the host did not alter
      OvCa adhesion, as determined utilizing mice harboring homozygous null mutations
      in either the Mmp2 or Mmp9 genes. Conversely, adhesion induced upregulation of
      MMP-2 mRNA in OvCa cells. MMP-2 inhibition in OvCa cells through pharmacological
      or antibody treatment prior to i.p. dissemination in nude mice significantly
      decreased tumor growth and metastasis and extended survival. MMP-2 enhanced
      peritoneal adhesion of OvCa cells through cleavage of ECM proteins fibronectin
      (FN) and vitronectin (Vn) into small fragments and increased binding of OvCa
      cells to these FN and Vn fragments and their receptors, alpha5beta1 and
      alphaVbeta3 integrin. These findings indicate that MMP-2 expressed by metastatic
      OvCa cells functionally regulates their attachment to peritoneal surfaces.

PMID- 18340379
TI  - Reversal of axonal loss and disability in a mouse model of progressive multiple
      sclerosis.
AB  - Axonal degeneration is an important determinant of progressive neurological
      disability in multiple sclerosis (MS). Thus, therapeutic approaches promoting
      neuroprotection could aid the treatment of progressive MS. Here, we used what we
      believe is a novel water-soluble fullerene derivative (ABS-75) attached to an
      NMDA receptor antagonist, which combines antioxidant and anti-excitotoxic
      properties, to block axonal damage and reduce disease progression in a chronic
      progressive EAE model. Fullerene ABS-75 treatment initiated after disease onset
      reduced the clinical progression of chronic EAE in NOD mice immunized with myelin
      oligodendrocyte glycoprotein (MOG). Reduced disease progression in ABS-75-treated
      mice was associated with reduced axonal loss and demyelination in the spinal
      cord. Fullerene ABS-75 halted oxidative injury, CD11b+ infiltration, and CCL2
      expression in the spinal cord of mice without interfering with antigen-specific T
      cell responses. In vitro, fullerene ABS-75 protected neurons from oxidative and
      glutamate-induced injury and restored glutamine synthetase and glutamate
      transporter expression in astrocytes under inflammatory insult. Glutamine
      synthetase expression was also increased in the white matter of fullerene ABS-75
      treated animals. Our data demonstrate the neuroprotective effect of treatment
      with a fullerene compound combined with a NMDA receptor antagonist, which may be
      useful in the treatment of progressive MS and other neurodegenerative diseases.

PMID- 18340380
TI  - Identification in rats of a programming window for reproductive tract
      masculinization, disruption of which leads to hypospadias and cryptorchidism.
AB  - Becoming a phenotypic male is ultimately determined by androgen-induced
      masculinization. Disorders of fetal masculinization, resulting in hypospadias or
      cryptorchidism, are common, but their cause remains unclear. Together with the
      adult-onset disorders low sperm count and testicular cancer, they can constitute
      a testicular dysgenesis syndrome (TDS). Although masculinization is well studied,
      no unifying concept explains normal male reproductive development and its
      abnormalities, including TDS. We exposed rat fetuses to either anti-androgens or
      androgens and showed that masculinization of all reproductive tract tissues was
      programmed by androgen action during a common fetal programming window. This
      preceded morphological differentiation, when androgen action was, surprisingly,
      unnecessary. Only within the programming window did blocking androgen action
      induce hypospadias and cryptorchidism and altered penile length in male rats, all
      of which correlated with anogenital distance (AGD). Androgen-driven
      masculinization of females was also confined to the same programming window. This
      work has identified in rats a common programming window in which androgen action
      is essential for normal reproductive tract masculinization and has highlighted
      that measuring AGD in neonatal humans could provide a noninvasive method to
      predict neonatal and adult reproductive disorders. Based on the timings in rats,
      we believe the programming window in humans is likely to be 8-14 weeks of
      gestation.

PMID- 18340381
TI  - IRF9 and STAT1 are required for IgG autoantibody production and B cell expression
      of TLR7 in mice.
AB  - A hallmark of SLE is the production of high-titer, high-affinity, isotype
      switched IgG autoantibodies directed against nucleic acid-associated antigens.
      Several studies have established a role for both type I IFN (IFN-I) and the
      activation of TLRs by nucleic acid-associated autoantigens in the pathogenesis of
      this disease. Here, we demonstrate that 2 IFN-I signaling molecules, IFN
      regulatory factor 9 (IRF9) and STAT1, were required for the production of IgG
      autoantibodies in the pristane-induced mouse model of SLE. In addition, levels of
      IgM autoantibodies were increased in pristane-treated Irf9 -/- mice, suggesting
      that IRF9 plays a role in isotype switching in response to self antigens.
      Upregulation of TLR7 by IFN-alpha was greatly reduced in Irf9 -/- and Stat1 -/- B
      cells. Irf9 -/- B cells were incapable of being activated through TLR7, and Stat1
      -/- B cells were impaired in activation through both TLR7 and TLR9. These data
      may reveal a novel role for IFN-I signaling molecules in both TLR-specific B cell
      responses and production of IgG autoantibodies directed against nucleic acid
      associated autoantigens. Our results suggest that IFN-I is upstream of TLR
      signaling in the activation of autoreactive B cells in SLE.

PMID- 18340382
TI  - Dopamine regulates endothelial progenitor cell mobilization from mouse bone
      marrow in tumor vascularization.
AB  - Mobilization of endothelial progenitor cells (EPCs) from the bone marrow and
      their subsequent participation in neovessel formation are implicated in tumor
      growth and neovascularization. As the neurotransmitter dopamine (DA) modulates
      adult endothelial cell function, we hypothesized that DA might have a regulatory
      role in mobilization of EPCs from the bone marrow niche. We show that there was a
      significant decrease in bone marrow DA content and an increase in EPC
      mobilization in tumor-bearing mice associated with tumor neovascularization. DA
      treatment of tumor-bearing mice inhibited EPC mobilization and tumor growth
      through its D2 receptors, as DA treatment failed to inhibit EPC mobilization in
      tumor-bearing mice treated with a specific DA D2 receptor antagonist and in tumor
      bearing mice lacking the D2 receptor. In addition, we found that DA, through D2
      receptors, exerted its inhibitory effect on EPC mobilization through suppression
      of VEGFA-induced ERK1/ERK2 phosphorylation and MMP-9 synthesis. These findings
      reveal a new link between DA and EPC mobilization and suggest a novel use for DA
      and D2 agents in the treatment of cancer and other diseases involving neovessel
      formation.

PMID- 18340383
TI  - A case of appropriate inappropriate device therapy: hyperkalemia-induced
      ventricular oversensing.
AB  - The present case describes a patient who received inappropriate, but potentially
      life-saving, therapy from her implantable cardioverter defibrillator (ICD) in the
      setting of acute hyperkalemia (plasma potassium concentration = 8 mM).
      Hyperkalemia was associated with the development of a slow sinusoidal ventricular
      tachycardia, at a rate of 100 beats/min to 125 beats/min (610 ms to 480 ms) in a
      patient who is pacemaker-dependent. There was associated fractionation of the ICD
      electrogram and T wave oversensing, leading to ventricular oversensing with
      resultant detection in the ventricular fibrillation rate zone. This was followed
      by shock therapy, even though the ventricular tachycardia rate was below the
      programmed detection rate of the ICD. The subsequent emergency treatment of the
      hyperkalemia normalized the electrogram, corrected the ventricular oversensing
      and arrhythmia, and restored rate-adaptive single-chamber ventricular pacing.

PMID- 18340384
TI  - Cor triatriatum: a multimodality imaging approach.
AB  - A 60-year-old man presented with congestive heart failure and was diagnosed with
      cor triatriatum after echocardiography. The various imaging modalities used for
      the definitive diagnosis of this condition are reviewed.

PMID- 18340385
TI  - Ventricular septal rupture complicating myocardial infarction: comprehensive
      assessment of cardiac coronary arteries, anatomy, perfusion and function by
      multidetector computed tomography.

PMID- 18340387
TI  - The relationship between physician supply, cardiovascular health service use and
      cardiac disease burden in Ontario: supply-need mismatch.
AB  - BACKGROUND: While health service use appears to be positively correlated with
      resource availability, no study has explored the interactions among health
      service supply, cardiovascular disease burden and health service use. The
      objective of the present study was to examine the relationship among
      cardiovascular evaluation and management intensity, physician supply and
      cardiovascular disease burden in the Canadian population. METHODS: The present
      cross-sectional, population-based study consisted of adult residents in Ontario
      in 2001. Cardiac evaluation and management intensity, the main outcome measure,
      was measured at the individual level, and consisted of receiving one or more of
      the following services: noninvasive cardiac testing, coronary angiography and
      statin use (the latter among individuals 65 years of age and older). Mortality
      was the secondary outcome measure. Cardiovascular disease burden, and
      cardiologist and primary care physician supply were measured at the regional (ie,
      county) level. Analyses were adjusted for age and sex using Poisson regression,
      accounting for regional clustering. RESULTS: Regional per capita cardiologist
      supply varied more than twofold across regions, but was inversely related to the
      regional cardiovascular disease burden (r=-0.34, P=0.01). Primary care physician
      supply was relatively evenly distributed across regions. Residents in areas with
      more cardiologists were more likely to receive some form of cardiac intervention
      (RR=1.074, 95% CI 1.066 to 1.082 per additional cardiologist per 100,000). Those
      in areas with more primary care physicians were also more likely to receive
      noninvasive cardiac testing (RR=1.056, 95% CI 1.051 to 1.061 per six additional
      primary care physicians per 100,000). However, the intensity of provision of
      cardiac health services was unrelated to regional cardiovascular disease burden
      and was not associated with improved survival. CONCLUSIONS: The mismatch between
      physician supply and cardiac disease burden may explain why cardiovascular health
      service use is neither concordant with the cardiovascular disease burden nor
      associated with mortality in the population. These results underscore the
      importance of physician service maldistribution and supply-sensitive care on the
      appropriateness of cardiac health service use.

PMID- 18340388
TI  - Treating the right patient at the right time: an innovative approach to the
      management of atrial fibrillation.
AB  - The Canadian Cardiovascular Society Access to Care Working Group recently
      published a series of commentaries on access to cardiovascular care in Canada.
      These commentaries included proposed minimally acceptable wait times for patients
      with atrial fibrillation (AF) to be assessed by a cardiologist or an
      electrophysiologist. To improve access to medical care for the patient with AF, a
      nurse clinician-based AF clinic was established in the Calgary Health Region
      (Alberta) in 2005. More than 330 patients had been referred at the time of
      writing. The time from referral to initial nurse assessment was 38+/-31 days, to
      physician review and establishment of a management plan was 66+/-49 days and to
      in-person specialist physician assessment was 80+/-55 days. These wait times are
      markedly shorter than historical wait times to see an arrhythmia specialist in
      the Calgary Region. As experience increased, wait times continued to shorten
      significantly. Preliminary data suggest that early assessment and patient
      education may reduce emergency department visits and hospitalizations for AF.
      This experience suggests that a nurse clinician-based AF clinic may provide
      earlier access to medical care and may improve health outcomes in the long term.

PMID- 18340389
TI  - Changes in lifestyle after hypertension diagnosis in Canada.
AB  - Lifestyle modification should be an important part of therapy when hypertension
      is first diagnosed, with or without starting antihypertensive medication. The
      objective of the present study was to determine the extent to which recently
      diagnosed hypertensive Canadians modify their lifestyles and to examine how
      lifestyle modification relates to antihypertensive medication use. The
      longitudinal National Population Health Survey in Canada was conducted between
      1994 and 2002, including five interview cycles at two-year intervals. During this
      time, 1281 persons reported hypertension in one cycle but not in the previous
      cycle, and were considered to be new hypertensive patients. Information collected
      included body mass index, smoking, alcohol consumption, physical inactivity and
      medication use. The main lifestyle modification associated with newly diagnosed
      hypertensive patients was smoking cessation, with a 18.6% relative risk reduction
      (RRR). A smaller change was seen in decreasing physical inactivity (RRR 6.2%).
      Persons not taking antihypertensive medication were not more likely to make
      lifestyle improvements. Paradoxically, new hypertensive patients showed increased
      numbers in the obese category (RRR -9.6%). Weight gain was especially marked
      among antihypertensive medication users and largest in female beta-blocker users
      (RRR -36.6%). If confirmed, this needs to be considered when prescribing to
      overweight people. In general, a greater effort is required to manage
      hypertension by lifestyle risk modification with or without antihypertensive
      medication.

PMID- 18340390
TI  - IMPPACT: Investigation of Medical Professionals and Patients Achieving Control
      Together.
AB  - OBJECTIVE: To determine whether home blood pressure monitoring (HBPM) led to
      physician-initiated medication titration and improved achievement of target BP
      levels compared with standard, office-based management. METHODS: Physicians were
      randomly assigned to a treatment group or a control group. Patients in the
      control group were monitored by their physician and were drug-adjusted according
      to the usual approach. In the treatment group, patients were given home BP
      monitors (UA-767P [A&D Medical/Lifesource, USA]), and drug dosing was adjusted
      according to HBPM readings and protocol. Long-acting diltiazem (240 mg/day) was
      added at baseline, which was adjusted as necessary (other medications were added
      if more than 360 mg/day of diltiazem was required). A final BP measurement was
      taken in the office after six weeks. RESULTS: Nineteen physicians were randomly
      assigned to the office BP monitoring group and 34 were assigned to the HBPM
      group. Of the 270 subjects recruited, 97 were in the office BP monitoring group
      and 173 were in the HBPM group. From baseline to the final visit, there was a
      statistically significant time by group interaction with lower BP in the HBPM
      group (P=0.034 for both systolic BP and diastolic BP). BP fell from 159/91+/
      11/10 mmHg at baseline in the HBPM group to 138/80+/-13/8 mmHg on the final
      visit, and from 160/88+/-14/10 mmHg to 141/78+/-10/9 mmHg in the control group.
      CONCLUSIONS: BP was lowered significantly in both groups, and to a statistically
      greater degree in the HBPM group. The Hawthorne effect might have led to altered
      care by the physicians with improvement in BP control in both groups.

PMID- 18340391
TI  - Is elevated serum ceruloplasmin level associated with increased risk of coronary
      artery disease?
AB  - BACKGROUND: An imbalance between the lipid peroxidation process and antioxidative
      protection is associated with the pathophysiology of coronary artery disease
      (CAD). The authors aimed to determine the relationship between the contributors
      of antioxidant protection, such as paraoxonase-1 (PON1) activity, albumin,
      vitamin C and ceruloplasmin (CP) levels, and lipid peroxidation indicators.
      METHODS: In the present study, the activity of PON1 was measured, together with
      serum concentrations of a variety of lipid constituents, albumin, vitamin C and
      CP levels, and lipid peroxidation indicators (conjugated dienes [CDs] and
      thiobarbituric acid-reactive substances [TBARS]). Data were gathered from 26
      nondiabetic, angiographically proven, Turkish CAD patients and 26 healthy
      controls living in the Antalya region (Turkey). RESULTS: CAD patients had
      significantly lower PON1 activity, high-density lipoprotein cholesterol, vitamin
      C and albumin concentrations, and higher CP, CD and TBARS concentrations than the
      controls. In the entire study population (n=52), serum CP levels were positively
      correlated with TBARS and CD levels, and negatively correlated with albumin and
      vitamin C levels, as well as with PON1 activity. On multiple logistic regression
      analysis, risk factors associated with CAD included high CP and low albumin
      levels. CONCLUSIONS: CAD patients and controls were matched for age and sex, and
      high CP and low albumin levels were found to be independent risk factors for CAD.
      The present data gathered from the study group living in the Antalya region
      verifies that in CAD patients, CP impairs the oxidant-antioxidant balance in
      favour of the oxidants.

PMID- 18340392
TI  - Symptom-to-door time in ST segment elevation myocardial infarction:
      overemphasized or overlooked? Results from the AMI-McGill study.
AB  - BACKGROUND: Ischemic time is a major determinant of infarct size in ST segment
      elevation myocardial infarction (STEMI). Emphasis is placed on reducing the door
      to-reperfusion therapy time component, whereas the symptom-to-door time is often
      overlooked. OBJECTIVES: To correlate the symptom-to-door time with left
      ventricular ejection fraction (LVEF) in patients with STEMI. METHODS: Acute
      Myocardial Infarction (AMI)-McGill was a cohort study of consecutive patients
      with STEMI who presented to three adult university hospitals. Multivariate linear
      regression was performed to correlate the symptom-to-door time with
      postinfarction LVEF adjusted for reperfusion method, prior myocardial infarction
      and components of the Thrombolysis In Myocardial Infarction (TIMI) risk score.
      RESULTS: There were 188 patients, with a mean age of 66 years. On arrival to
      hospital, 23% of patients were in Killip class II to IV and 87% received
      reperfusion therapy (20% fibrinolytic therapy and 67% primary percutaneous
      coronary intervention). The median symptom-to-door time was 120 min (first
      quartile: 60 min, third quartile: 290 min) and the median door-to-reperfusion
      therapy time was 93 min (first quartile: 54 min, third quartile: 155 min). Three
      variables were independently correlated with LVEF in the study's regression
      model: symptom-to-door time (beta: -0.66, 95% CI -1.18 to -0.14; P=0.01), Killip
      class II to IV on arrival (beta: -6.43, 95% CI -11.87 to -0.99; P=0.02) and
      anterior territory of the infarction (beta: -5.86, 95% CI -10.55 to -1.18;
      P=0.02). CONCLUSIONS: Symptom-to-door time was negatively correlated with
      postinfarction LVEF in patients with STEMI. Strategies to shorten this delay,
      such as educating high-risk patients about the symptoms of AMI, should be
      considered.

PMID- 18340393
TI  - Two decades of cardiac transplantation at the Montreal Heart Institute.
AB  - BACKGROUND: The first heart transplantation in Canada was performed in 1968 at
      the Montreal Heart Institute (Montreal, Quebec). After nine patients transplanted
      in the precyclosporine era, the program was stopped. With the advent of
      cyclosporine, the program was reactivated in 1983. OBJECTIVE: To review the
      experience of the Montreal Heart Institute with heart transplantation between
      1983 and 2005. METHODS: Three hundred patients underwent heart transplantation
      and were followed at the transplant clinic. Patients were divided into two
      groups: group 1--first decade (1983 to 1993, n=145) and group 2--second decade
      (1994 to 2005, n=155). RESULTS: There were 125 men (86%) and 20 women (14%) with
      a mean age of 45+/-10 years in group 1 compared with 118 men (76%) and 37 women
      (24%) with a mean age of 48+/-12 years in group 2 (P=0.03 and P=0.02,
      respectively). Indications for transplantation included congestive heart failure
      and/or ischemic heart disease in the majority of patients of both groups, with
      83% in group 1 and 73% in group 2, respectively. In group 1, 30 patients (21%)
      required preoperative pharmacological support and 13 patients (9%) were on
      mechanical support compared with 16 (10%) and 34 (22%) patients in group 2
      (P<0.01). The mean age of donors was 27+/-10 years and 34+/-13 years in groups 1
      and 2, respectively (P<0.01). Major causes of mortality for donors included a
      motor vehicle accident in 65 cases (45%) and brain hemorrhage in 43 cases (30%)
      in group 1 compared with 34 cases (22%) and 68 cases (44%) in group 2 donors
      (P<0.01). The one-, five- and 10-year actuarial survival rates were 86%, 77% and
      71%, respectively, in group 1 compared with 84%, 80% and 68%, respectively, in
      group 2 (P=0.95). The one-, five- and 10-year freedom from rejection rates were
      35%, 28% and 25%, respectively, in group 1 compared with 41%, 36% and 33%,
      respectively, in group 2 (P=0.13). The one-, five- and 10-year freedom from
      infection rates were 38%, 24% and 17%, respectively, in group 1 compared with
      37%, 23% and 19%, respectively, in group 2 (P=0.72). The one- and five-year
      freedom from graft coronary artery disease rates were 93% and 67%, respectively,
      in group 1 compared with 88% and 81%, respectively, in group 2 (P<0.01). The one
      , five- and 10-year cancer-free survival rates were 98%, 91% and 73%,
      respectively, in group 1 compared with 98%, 90% and 77%, respectively, in group 2
      (P=0.76). CONCLUSIONS: Patients who underwent heart transplantation in the second
      decade of the investigators' experience were older and in worse preoperative
      clinical condition; the donors were also older. However, survival and event-free
      survival rates remained similar throughout both periods.

PMID- 18340394
TI  - Detection of plaque rupture using 64-slice multidetector row computed tomography.
AB  - The present case report describes a 37-year-old man who presented to the
      emergency room with symptoms of a myocardial infarction but no high-grade
      stenosis on conventional catheter angiography. Consecutive multidetector row
      computed tomography of the coronary arteries showed an intimal flap along a
      fibrous plaque formation in the left anterior descending artery. This finding was
      found to represent a plaque rupture, and the lesion was treated with an 18 mm
      stent. Multidetector row computed tomography helped to correctly position the
      stent by identifying the exact location of the rupture along the long plaque
      formation.

PMID- 18340395
TI  - Primary right ventricular osteosarcoma.
AB  - A 41-year-old man suffering from dyspnea on exertion was found to have a mass
      located on the right ventricle. Resection of the tumour required reconstruction
      of the right ventricular outflow tract and replacement of the pulmonary valve.
      Histopathology confirmed the diagnosis of high-grade osteosarcoma.

PMID- 18340396
TI  - A broken heart: right-to-left shunt in the setting of normal cardiac pressures.
AB  - A patent foramen ovale (PFO) is a common structural cardiac variant occurring in
      approximately 30% of the general population. Patients are usually asymptomatic
      because the defect is flap-like and does not permit significant left-to-right
      shunting. However, pathological conditions that result in cardiac rotation or
      higher than normal right atrial pressures can reverse the normal left atrial to
      right atrial pressure gradient and cause a right-to-left shunt through a PFO. If
      the right-to-left shunt is persistent, systemic hypoxemia or paradoxical emboli
      may result. The present report describes a case of refractory hypoxemia in a
      critically ill patient with a PFO who had a right-to-left shunt with normal right
      sided cardiac pressures.

PMID- 18340397
TI  - Do needs, symptoms or disability of outpatients with schizophrenia influence
      family burden?
AB  - BACKGROUND: Most needs of outpatients with schizophrenia are met by the family.
      This could cause high levels of family burden. The objective of this study is to
      assess the relationship between the patients' needs and other clinical and
      disability variables and the level of family burden. METHOD: A total sample of
      231 randomly selected outpatients with schizophrenia was evaluated with the
      Camberwell Assessment of Needs, Positive and Negative Syndrome Scale, Global
      Assessment of Functioning and Disability Assessment Scale. A total of 147
      caregivers also answered the objective and subjective family burden questionnaire
      (ECFOS-II). Correlations between total number of needs and family burden, t tests
      between presence or absence of need for each domain of family burden and
      regression models between family burden and needs, symptoms, disability and
      sociodemographic variables were computed. RESULTS: The number of patients' needs
      was correlated with higher levels of family burden in daily life activities,
      disrupted behaviour and impact on caregiver's daily routine. The patients' needs
      most associated with family burden were daytime activities, drugs, benefits, self
      care, alcohol, psychotic symptoms, money and looking after home. In a regression
      model, a higher number of needs, higher levels of psychopathology and disability,
      being male and older accounted for higher levels of family burden. CONCLUSION:
      Patients with schizophrenia with more needs cause greater family burden but not
      more subjective concerns in family members. The presence of patients' needs
      (daytime activities, alcohol and drug), severity of psychotic symptoms and
      disability are related to higher levels of family burden.

PMID- 18340398
TI  - Alcohol use prevalence and sociodemographic correlates of alcohol use in a
      university student sample in Turkey.
AB  - BACKGROUND: This study is a survey to determine prevalence and sociodemographic
      correlates of drinking problems among students from five university centres in
      Turkey. METHOD: Using an anonymous self-administered questionnaire and the CAGE
      Questionnaire for alcohol use problems, 1,720 students were surveyed. RESULTS: Of
      the whole student sample 63.3% reported that they had ever tried drinking
      alcohol, and 48.5% had used alcohol in the past year. Sixty five percent of the
      students had been drinking once a month or more frequently. The overall
      prevalence of alcohol use problems according to CAGE2+ was 9.7% (19.9% among the
      students who used alcohol in the past year). In multivariate analysis, male
      students tended to have problems with alcohol about three times more than
      females. Living in the dormitory seemed to be protective in terms of frequent
      drinking, and as educational level of the parents increased, the odds of drinking
      at least once a month increased. Students whose mothers were illiterate or
      primary school graduate tended to give more positive answers to the Cut-down,
      Annoyed and Guilty items. The odds of giving a positive answer to the Cut-down
      item among those living alone was greater than the other residence groups.
      Predictors of positive answer to the Eye-opener item were male gender, living
      alone at home, and residence of the family being in a foreign country. Paternal
      educational level being in the illiterate/primary school category was
      significantly related with more positive answers to the Guilty item. CONCLUSIONS:
      Drinking problems among university students in Turkey are more prevalent when
      compared with prevalence rates shown in other surveys in Turkey. Alternative ways
      of socialization should be provided for the university youth in order to prevent
      alcohol use problems in the future.

PMID- 18340399
TI  - Determination of solubilities and n-octanol/water partition coefficients and QSPR
      study for substituted phenols.
AB  - A shake-flask method was employed to determine the water solubility (-lgS (w))
      and n-octanol/water partition coefficient (lgK (ow)) of 20 substituted phenols at
      298.15 K. And optimized calculation was carried out at B3LYP/6-311G** level with
      DFT method. Afterwards the obtained parameters were taken as theoretical
      descriptors to establish the QSPR models for predicting -lgS (w) and lgK (ow), in
      which the conventional correlation coefficients (R (2)) are 0.9800 and 0.9941,
      respectively. The two models were further validated by variance inflation factors
      (VIF) and t-test. Upon comparison, the stability and predictive power are more
      advantageous than those based on AM1 molecular orbital method and molecular
      connectivity method.

PMID- 18340400
TI  - Serologic and hexon phylogenetic analysis of ruminant adenoviruses.
AB  - The objectives of this study were to determine the antigenic relationship among
      ruminant adenoviruses and determine their phylogenetic relationship based on the
      deduced hexon gene amino acid sequence. Results of reciprocal cross
      neutralization tests demonstrated antigenic relationships in either one or both
      directions among bovine adenovirus type 6 (BAdV-6), BAdV-7, ovine adenovirus type
      7 (OAdV-7), caprine adenovirus type 1 (GAdV-1), and deer adenovirus (Odocoileus
      adenovirus 1, OdAdV-1). No antigenic cross-reactivity was observed among BAdV-1
      through -5, and -8 and the other putative ruminant adenoviruses. Two PCR primer
      sets, one for mastadenovirus and atadenovirus that amplified an approximately
      2,700-bp region in the hexon genes were used for comparative studies.
      Phylogenetic analysis of the deduced hexon amino acid sequences clustered the
      ruminant adenoviruses on the Mastadenovirus and Atadenovirus genus branches of
      the Adenoviridae tree. The recent classification of BAdV-6, and -7 as members of
      the genus Atadenovirus was supported by phylogenetic distance matrix analysis of
      their deduced hexon amino acid sequences. Further, we propose that BAdV-6 and -7
      be recognized as members of new Atadenovirus species, Bovine adenovirus E and
      Bovine adenovirus F, respectively. Phylogenetic analysis of OdAdV-1 places this
      virus in the genus Atadenovirus with a proposed new species Odocoileus adenovirus
      A. OAdV-6 and GAdV-2 are proposed as members of new Mastadenovirus species Ovine
      adenovirus C and Goat adenovirus A, respectively.

PMID- 18340401
TI  - Characterization of a thermostable dihydrodipicolinate synthase from
      Thermoanaerobacter tengcongensis.
AB  - Dihydrodipicolinate synthase (DHDPS) catalyses the first reaction of the (S)
      lysine biosynthesis pathway in bacteria and plants. The hypothetical gene for
      dihydrodipicolinate synthase (dapA) of Thermoanaerobacter tengcongensis was found
      in a cluster containing several genes of the diaminopimelate lysine-synthesis
      pathway. The dapA gene was cloned in Escherichia coli, DHDPS was subsequently
      produced and purified to homogeneity. The T. tengcongensis DHDPS was found to be
      thermostable (T0.5=3 h at 90 degrees C). The specific condensation of pyruvate
      and (S)-aspartate-beta -semialdehyde was catalyzed optimally at 80 degrees C at
      pH 8.0. Enzyme kinetics were determined at 60 degrees C, as close as possible to
      in vivo conditions. The established kinetic parameters were in the same range as
      for example E. coli dihydrodipicolinate synthase. The specific activity of the T.
      tengcongensis DHDPS was relatively high even at 30 degrees C. Like most
      dihydrodipicolinate synthases known at present, the DHDPS of T. tengcongensis
      seems to be a tetramer. A structural model reveals that the active site is well
      conserved. The binding site of the allosteric inhibitor lysine appears not to be
      conserved, which agrees with the fact that the DHDPS of T. tengcongensis is not
      inhibited by lysine under physiological conditions.

PMID- 18340402
TI  - Congenital central hypoventilation syndrome with hyperinsulinism in a preterm
      infant.
AB  - Congenital central hypoventilation syndrome (CCHS), a rare disorder typically
      presenting in the newborn period, results in over 90% of cases from PHOX2B
      polyalanine repeat mutations. It is characterized by alveolar hypoventilation,
      symptoms of autonomic nervous system dysregulation, and in a subset of cases
      Hirschsprung's disease and, later, tumors of neural crest origin. We describe a
      preterm infant with severe phenotype of CCHS and hyperinsulinism. A novel de novo
      heterozygote missence mutation (Gly68Cys) in the PHOX2B gene could be identified.
      Based on the observation of three patients presenting with the combination of
      congenital hyperinsulinism and CCHS, hyperinsulinism might represent an
      additional clinical feature of CCHS.

PMID- 18340403
TI  - Structural study on mutant alpha-L-iduronidases: insight into
      mucopolysaccharidosis type I.
AB  - To elucidate the basis of mucopolysaccharidosis type I (MPS I), we constructed
      structural models of mutant alpha-L: -iduronidases (IDUAs) resulting from 33
      amino acid substitutions that lead to MPS I (17 severe, eight intermediate, and
      eight attenuated). Then, we examined the structural changes in the enzyme protein
      by calculating the number of atoms affected and determined the root-mean-square
      distance (RMSD) and the solvent-accessible surface area (ASA). In the severe MPS
      I group, the number of atoms influenced by a mutation and the average RMSD value
      were larger than those in the attenuated group, and the residues associated with
      the mutations identified in the severe group tended to be less solvent accessible
      than those in the attenuated group. The clinically intermediate phenotype group
      exhibited intermediate values for the numbers of atoms affected, RMSD, and ASA
      between those in the severe group and those in the attenuated group. The results
      indicated that large structural changes had occurred in the core region in the
      severe MPS I group and small ones on the molecular surface in the attenuated MPS
      I group. Color imaging revealed the distributions and degrees of the structural
      changes caused by representative mutations for MPS I. Thus, structural analysis
      is useful for elucidating the basis of MPS I. As there was a difference in IDUA
      structural change between the severe MPS I group and the attenuated one, except
      for a couple of mutations, structural analysis can help predict the clinical
      outcome of the disease.

PMID- 18340404
TI  - Methylenetetrahydrofolate reductase gene polymorphisms and lung cancer: a meta
      analysis.
AB  - So far, case-control studies on the association between methylenetetrahydrofolate
      reductase (MTHFR) gene polymorphisms and lung cancer provide controversial or
      inconclusive results. To clarify the effect of MTHFR polymorphisms on the risk of
      lung cancer, a meta-analysis of all case-control observational studies was
      performed. The studies provided 5,111/6,415 cases/controls for C677T and
      5,087/6,232 cases/controls for A1298C. The heterogeneity (P=0.0001, I(2)=76.6%)
      for C677T among the eight studies was extreme. Cluster analyses based on the
      frequencies of the C677T genotype of the control group in each study revealed
      that the studies could not cluster together according to their ethnicity. The
      random effects (RE) model showed that the 677T allele was not associated with the
      risk of lung cancer compared with the C allele [OR=1.12, 95% confidence interval
      (CI) (0.97-1.28), P=0.12]. The contrast of homozygotes, recessive model, dominant
      model produced the same pattern of results as the allele contrast. In regard to
      the A1298C polymorphism, there was no heterogeneity among the seven studies
      comparing the C versus the A allele (P=0.24, I(2)=24.4%), but no significant
      association was detected by the RE model or the fixed effects model [FE odds
      ratio (OR)=0.99 (0.93-1.05) and RE OR=1.00 (0.92-1.08)]. The effect of MTHFR
      polymorphisms (C677T, A1298C) on the risk of lung cancer was undetectable, even
      though analyzed on a relatively good number of subjects (totally 11,526 subjects)
      by meta-analysis (statistical power = 93.9%). Although MTHFR polymorphisms were
      associated with the risk of colorectal cancer, leukemia, and gastric cancer
      supported by other meta-analysis, our pooled data suggest no evidence for a major
      role of these two variants in carcinogenesis of lung cancer. The results implied
      that different tumors evolve by different pathological pathways and the roles of
      MTHFR in cancer is determined by its target genes.

PMID- 18340405
TI  - Pilocytic astrocytoma of the spinal cord in an adult.

PMID- 18340406
TI  - Uptake of Pb(2+ )by a cyanobacterium belonging to the genus Synechocystis,
      isolated from East Kolkata Wetlands.
AB  - East Kolkata Wetlands is a conserved wetland utilizing sewage and garbage,
      generated by Kolkata Municipal Corporation area for cultivation purpose.
      Cyanobacteria are the photosynthetic prokaryotes having bioremedial capacity. We
      have isolated a cyanobacterium from the sewage recycling fish-pond of East
      Kolkata Wetlands. Partial sequence of 16S rDNA gene of the isolated strain showed
      100% similarity with that of genus Synechocystis. Isolated strain and
      Synechocystis sp. PCC6803 survived up to 300 mug ml(-1) Pb(2+ )and growth was
      completely inhibited at 400 mug ml(-1) Pb(2+). All experiments were carried out
      with 100 mug ml(-1) Pb(2+) in which growth was the maximum. 91.67% of the total
      Pb(2+) got adsorbed to the outer surface of the cell and 1% of the total Pb(2+)
      entered the cell of the isolated strain as estimated by atomic absorption
      spectrometry, but in Synechocystis sp. PCC6803 72.72% adsorbed and 0.96%
      penetrated. Intracellular and periplasmic depositions of Pb(2+) were observed in
      both the strain. A filamentous structure developed outside the cell wall of the
      isolated cyanobacterium, but very little change was observed in Synechocystis sp.
      PCC6803. ZiaR-SmtB like regulator gene was expressed in both the strains after
      Pb(2+) induction. The cDNA sequence of ZiaR of the isolated cyanobacterium shows
      100% homology with that of Synechocystis sp. PCC6803. Upon Pb(2+) induction,
      expression of SOD gene increased. cDNA sequence of the SOD gene from the isolated
      strain showed 98% homology with that of Synechocystis sp. PCC6803. Enzymatic
      activity of catalase and SOD was also increased. No DNA damage was monitored upon
      induction with Pb(2+).

PMID- 18340407
TI  - Rofecoxib potentiates the anticonvulsant effect of topiramate.
AB  - The present study examines the effect of rofecoxib in combination with topiramate
      (a newer antiepileptic) against PTZ (80 mg/kg, i. p.)-induced chemoconvulsions in
      mice. Pretreatment with rofecoxib (1.0 and 5.0 mg/kg., i. p.) or topiramate (50
      and 100 mg/kg., i. p.) dose dependently protected the animals against PTZ-induced
      convulsions. However, the lower dose of neither rofecoxib (0.5 mg/kg., i. p.) nor
      topiramate (25 mg/kg., i. p.) modified the latency of any of the phase of PTZ
      induced convulsions. When a subeffective doses of rofecoxib (0.5 mg/kg, i. p.)
      was coadministered with a subprotective dose of topiramate (25 mg/kg, i. p.),
      there was no increase in onset latency of myoclonic jerks but an increase in the
      latency for clonus and extensor phase were observed. Rofecoxib may be used as an
      adjunct therapy with topiramate in the treatment of epilepsy.

PMID- 18340408
TI  - Leptin protection of salivary gland acinar cells against ethanol cytotoxicity
      involves Src kinase-mediated parallel activation of prostaglandin and
      constitutive nitric oxide synthase pathways.
AB  - Leptin, a pleiotropic cytokine secreted by adipocytes but also identified in
      salivary glands and saliva, is recognized as an important element of oral mucosal
      defense. Here, we report that in sublingual salivary glands leptin protects the
      acinar cells of against ethanol cytotoxicity. We show that ethanol- induced
      cytotoxicity, characterized by a marked drop in the acinar cell capacity for NO
      production, arachidonic acid release and prostaglandin generation, was subject to
      suppression by leptin. The loss in countering capacity of leptin on the ethanol
      induced cytotoxicity was attained with cyclooxygenase inhibitor, indomethacin and
      nitric oxide synthase (cNOS) inhibitor, L-NAME, as well as PP2, an inhibitor of
      Src kinase. Indomethacin, while not affecting leptin-induced arachidonic acid
      release, caused the inhibition in PGE2 generation, pretreatment with L-NAME led
      to the inhibition in NO production, whereas PP2 exerted the inhibitory effect on
      leptin-induced changes in NO, arachidonic acid, and PGE2. The leptin-induced
      changes in arachidonic acid release and PGE2 generation were blocked by ERK
      inhibitor, PD98059, but not by PI3K inhibitor, wortmannin. Further, leptin
      suppression of ethanol cytotoxicity was reflected in the increased Akt and cNOS
      phosphorylation that was sensitive to PP2. Moreover, the stimulatory effect of
      leptin on the acinar cell cNOS activity was inhibited not only by PP2, but also
      by Akt inhibitor, SH-5, while wortmannin had no effect. Our findings demonstrate
      that leptin protection of salivary gland acinar cells against ethanol
      cytotoxicity involves Src kinase-mediated parallel activation of MAPK/ERK and Akt
      that result in up-regulation of the respective prostaglandin and nitric oxide
      synthase pathways.

PMID- 18340409
TI  - Cyto-protective and immunomodulating effect of Curcuma longa in Wistar rats
      subjected to carbon tetrachloride-induced oxidative stress.
AB  - A comparison of crude curcuminoid extract and purified curcumin was made to
      evaluate hepato- and immunoprotective effect of Curcuma longa (turmeric)
      Zingiberaceae. Carbon tetrachloride (CCl4) induced cellular hepatic damage was
      evaluated by transmission electron microscopy, hepatic enzymes and thiobarbituric
      acid reactive species (TBAR) values. A selective cytolytic effect of CCl4 was
      observed among immature (PNA+) thymocytes and peripheral helper (CD4+) T
      lymphocytes in spleen and was paralleled by a significant reduction in CD25, CD71
      and Con A receptor expression. Treatment with curcuminoid crude extract at two
      different doses, showed a significant cellular recovery among hepatocytes, which
      was reflected in a reduction of hepatic enzymes and TBAR values. A significant
      restoration of lymphocyte viability and CD25, CD71 and Con A receptor expression
      in both immature (PNA+) thymocytes and splenic helper (CD4+) T lymphocytes was
      observed. Turmeric crude extract, at both low and high dose, was found to be more
      efficient as compared to purified curcumin.

PMID- 18340410
TI  - Enhanced production of high-quality biomass, delta-aminolevulinic acid,
      bilipigments, and antioxidant capacity of a food alga Nostochopsis lobatus.
AB  - The growing interest in natural food has raised the global demand for
      nutraceuticals. We studied enhanced production of biomass, delta-aminolevulinic
      acid (delta-ALA), bili pigments and antioxidant capacity of a food alga
      Nostochopsis lobatus in a full-factorial (three level) design with supplemental
      Zn, glutamine, and Zn + glutamine in batch culture. Production of biomass,
      pigments, and antioxidant capacity all were higher under immobilized cell
      cultures in comparison to free cell cultures. Maximum biomass (2,390 mg dry wt l(
      1)), delta-ALA (2.715 microg mg(-1) dry wt h(-1)), phycocyanin (98.50 mg g(-1)
      dry wt), phycoerythrin (158.0 mg g(-1) dry wt), and antioxidant capacity (140.50
      mumoles ascorbic acid equivalent capacity g(-1) fresh wt) were recorded when Zn
      and glutamine were supplemented together in the growth medium at pH 7.8. These
      effects were found to be significantly related to the activities of glutamine
      synthetase (GS(max): 490.2 nmoles mg protein(-1) min(-1)), glutamate synthase
      (GOGAT(max): 27.0 nmoles mg protein(-1) min(-1)), and glutamate dehydrogenase
      (GDH(max): 159.9 nmoles mg protein(-1) min(-1)). This study shows that N. lobatus
      could be a promising bioresource for the production of nutritionally rich
      biomass, delta-ALA, bili pigments, and antioxidants. Use of immobilized cells in
      batch culture supplemented with Zn and glutamine could be an effective approach
      for scaling up production for commercial use.

PMID- 18340411
TI  - Combined intravenous and intraarterial revascularization therapy using MRI
      perfusion/diffusion mismatch selection for acute ischemic stroke at 3-6 h after
      symptom onset.
AB  - BACKGROUND AND PURPOSE: Intravenous (IV) thrombolysis with recombinant tissue
      plasminogen activator (rt-PA) has demonstrated favorable clinical outcomes in a 3
      6 h window in patients selected with perfusion/diffusion mismatch. However, the
      advantages of combined IV and intraarterial (IA) thrombolysis after 3 h of stroke
      onset are unexplored. METHODS: Acute ischemic stroke patients with persistent
      occlusion of intracranial large arteries were screened prospectively for
      thrombolysis by evaluating perfusion/diffusion mismatch on MRI. The IV rt-PA was
      initiated within 3-6 h, and additional urokinase (UK) was then administered via
      the IA route after angiography. RESULTS: Four patients had middle cerebral artery
      occlusion and one patient had an internal carotid artery occlusion. The median
      time from the symptom onset to the initiation of IV therapy and to the initiation
      of IA treatment was 215 +/- 30 min and 292 +/- 41 min, respectively. The median
      National Institutes of Health Stroke Scale (NIHSS) scores were as follows:
      initial, 13; immediately after IA treatment, 8; at 24 h, 5; and at 7 days, 3. The
      Thrombolysis in Myocardial Infarction (TIMI) score after the completion of
      thrombolysis was 2-3. Four patients without intracerebral hemorrhage recovered
      completely or exhibited mild disability and one patient with hemorrhage also
      demonstrated a favorable outcome. CONCLUSION: This preliminary result suggests
      that if a significant perfusion/diffusion mismatch on MRI is identified, a
      sequential combination thrombolysis of IV rt-PA and IA UK is potentially
      beneficial in moderate to severe acute ischemic stroke patients who are treated
      within 3-6 h after symptom onset.

PMID- 18340412
TI  - [Sperm retrieval by transrectal electro-ejaculation in primary anorgasmy].

PMID- 18340413
TI  - [Pilomatrixoma. An important differential diagnosis of cystic tumors in adults].

PMID- 18340414
TI  - [Sexual self-reflection in patients with atopic dermatitis and psoriasis].
AB  - OBJECTIVE: The aim of this study was to evaluate the differences between the
      Sexual Self-Reflection in patients with atopic dermatitis and psoriasis from a
      group of healthy controls. Furthermore the influence of coping with the disease
      and pruritus on the patients' sexuality was studied METHODS: Patients with atopic
      dermatitis (n=38), psoriasis (n=31) and healthy controls (n=33) were tested with
      various psychological questionnaires. The German questionnaire for partnership
      attributes (PFB), Marburg questionnaire for coping with skin diseases (MHF) and
      questionnaire for pruritus and cognition (JKF), and sexual self-concept
      questionnaire (MSSCQ) served as psychometric measures. RESULTS: Patients with
      atopic dermatitis showed more fears of sex, with pruritus being the main factor,
      so that controlling pruritus should also improve sexual experience. Patients with
      psoriasis and sexual problems showed significantly more social fears and
      avoidance. CONCLUSION: Appropriate psychosomatic care and educational programs
      including the therapy of social fears, avoidance and pruritus may also improve
      sexual life in patients with psoriasis or atopic dermatitis.

PMID- 18340415
TI  - [Psychodermatology].

PMID- 18340416
TI  - [Hypertrichosis].
AB  - Hypertrichosis denotes growth of hair on any part of the body in excess of the
      amount usually present in persons of the same age, race, and sex, excluding
      androgen-dependent hair growth. Hypertrichosis may be an isolated finding or
      associated with a syndrome, be associated with additional congenital anomalies or
      a marker for systemic disease. In order to diagnose it accurately, the age of
      onset, type, localization and pattern of hair growth, associated disorders,
      medications and perhaps associated anomalies and family history should be
      considered. Even though hypertrichosis usually has limited medical significance,
      it often causes cosmetic embarrassment, often resulting in a significant
      emotional burden. Treatment options are available, though limited in terms of
      efficacy and patient satisfaction. No single method of hair removal is
      appropriate for all body locations and patients, and the one adopted will depend
      on the type, area, and amount of excessive hair growth, as well as on the age,
      sex, and personal preference of the patient. Patients with hypertrichosis should
      be adequately advised of the treatment modalities. These include cosmetic
      procedures (bleaching, trimming, shaving, plucking, waxing, chemical epilatories,
      electrosurgical epilation), and hair removal using light sources and lasers.

PMID- 18340417
TI  - [Unusual causes of biphonation].
AB  - Biphonation or diplophonia can be caused by several mechanisms. Although helpful
      for communication in some animals, biphonation in humans is usually perceived as
      increased roughness. Herein we report two unusual causes for biphonation. In the
      first case, a woman suffered from vocal fold bamboo nodes. These decoupled the
      anterior from the posterior part of the vocal folds, leading to an intermittent
      anterior-posterior vibration pattern during phonation. In the second case, a
      patient underwent a pitch-raising operation. Postoperatively we saw a transversal
      fixation of the vocal fold mucosa caused by a suture. This fixation led to two
      separated "neo" glottides, one being in the anterior third and the other in the
      posterior third of the vocal folds.

PMID- 18340418
TI  - [Chronic rhinosinusitis with septal perforation. Differential diagnostic
      considerations].
AB  - Chronic rhinosinusitis together with nasal septal perforation with or without
      pain of the nasal skeleton and without previous trauma or surgery point toward
      the possible diagnosis of Wegener's granulomatosis. However, nasal biopsy and
      serologic testing remain inconclusive in many patients. The otolaryngologist's
      role in this situation is to initiate, in close cooperation with a
      rheumatologist, therapy with sulfatrimethoprim, as well as with
      immunosuppressants if necessary. This helps stabilize the symptomatology and may
      prevent progressive systemic disease.

PMID- 18340419
TI  - [Update on computer- and mechatronic-assisted head and neck surgery in Germany].
AB  - A consequence of the ongoing advances in medical navigation is the development of
      so-called mechatronic assistant systems. Up to now, medical navigation had been
      used only for additional intrasurgical orientation. But improvements in accuracy
      in imaging and medical navigation can exceed the surgeon's possible manual
      accuracy of surgical manipulation. In such cases, mechatronic assistant systems
      can supplement certain surgical procedures in order to obtain the required
      precision, such as for positioning of implants. The development and possible use
      of such mechatronic assistant systems in the head and neck, as well as
      improvements in the accuracy of medical navigation, are the focus of several
      working groups. For coordinating and adapting the various research projects,
      different research groups were called to present their current projects and
      results in the context of ASKRA (working group for skull-base and craniofacial
      surgery of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery)
      workshops at the German Society for Computer- and Robot-Assisted Surgery (CURAC)
      convention on 14 October 2006 in Hanover. Different projects were presented, with
      topics including navigated controlled assistant systems for the frontal and
      lateral skull base, possibilities for sonographic-induced bone measurement, and
      requirements for high-precision surgery of the skull base.

PMID- 18340420
TI  - [Granular cell tumor of the larynx: a case report].
AB  - Granular cell tumors are benign subcutaneous or submucosal lesions of neurogenic
      origin. They are quite commonly found in the head and neck region, particularly
      in the tongue. However, only about 200 cases of laryngeal granular cell tumors
      have been reported so far. Most laryngeal granular cell tumors are located in the
      posterior part of the vocal fold and in the posterior commissure. Differentiation
      from inflammatory as well as from malignant lesions is possible only by biopsy.
      The treatment of choice is complete excision. However, tumor extension and
      expected morbidity of the surgery will inevitably influence the extent of the
      resection. Recurrences after complete excision are rare.

PMID- 18340421
TI  - [Metastasis to the lateral skull base].
AB  - BACKGROUND: Tumours and metastases of the lateral skull base are rare findings.
      Clinically, the progressive involvement of ipsilateral cranial nerves is
      important. CASE REPORT: A 69-year-old man presented with headache and palsies of
      the facial nerve and nerve VI. Furthermore, he had hearing loss and hypaesthesia
      of the trigeminal nerve (V3). Four months previously, laser therapy for carcinoma
      of the trachea (cT4 cN3 cM0) had been done. Computed tomography (CT) and magnetic
      resonance imaging (MRI) revealed an intrapetrosal mass with destruction of the
      lateral skull base. The findings suggested a metastasis of the tracheal
      carcinoma. We performed a mastoidectomy with specimen collection, and the
      pathological analysis revealed infiltration of a squamous cell carcinoma. The
      patient died within 3 weeks after radiotherapy with palliative intention despite
      malignant progression. CONCLUSION: The diagnosis and therapy of metastases to the
      lateral skull base is an interdisciplinary challenge. CT and MRI scans are
      essential for planning further procedures. In cases of headache and cranial nerve
      palsies, a metastasis to the lateral skull base must be considered in the
      differential diagnosis.

PMID- 18340422
TI  - [DNA-protective potential of polyphenols in human mucosa cell cultures].
AB  - BACKGROUND: The concept of field cancerization in the head and neck offers an
      excellent basis for chemopreventive interventions. Within the last few years,
      polyphenols, the most abundant phytochemicals in our diet, have been identified
      as interesting chemopreventive agents based on their multiple actions. This study
      was designed to add more experimental data regarding the chemopreventive features
      of epigallocatechin gallate (EGCG) and tannin (TA) in cultures of fresh biopsied
      tissue to epidemiologic studies and animal and cell line experiments. MATERIALS
      AND METHODS: Miniorgan cultures (MOC) were produced from oropharyngeal mucosa
      cubes about 1 mm(3), epithelialized and with their tissue structure preserved.
      The MOC were incubated with EGCG (0.1 and 5 microM) and TA (1 and 5 microM) for
      30 min on three consecutive days. On the 3rd day, DNA damage was introduced with
      metabolically activated tobacco carcinogen benzo[a]pyren-7,8-dihydrodiol-9,10
      epoxid (BPDE) [9 microM] for 60 min. The resulting DNA damage was measured with
      alkaline single-cell microgel electrophoresis (comet assay) and quantified using
      the olive tail moment (OTM). RESULTS: By incubating MOC with the polyphenols, the
      DNA damage caused by BPDE was significantly decreased at all concentrations.
      CONCLUSION: To our knowledge, this is the first test using cell cultures produced
      from fresh biopsies that demonstrates ECGC and TA as promising chemopreventive
      agents and confirms nutritional studies.

PMID- 18340423
TI  - [Septal perforation and palatal defect].

PMID- 18340424
TI  - A highly bone marrow metastatic murine breast cancer model established through in
      vivo selection exhibits enhanced anchorage-independent growth and cell migration
      mediated by ICAM-1.
AB  - To understand the mechanisms underlying bone marrow metastasis precisely, we
      established the highly metastatic 4T1E/M3 murine breast cancer cell line. 4T1
      murine breast cancer cells were transfected with the neomycin resistance gene,
      selected in G418, intravenously injected into mice, and harvested from bone
      marrow. By repeating this protocol three times, we established the 4T1E/M3 cells.
      The clonality of 4T1E/M3 cells was markedly high confirmed by genomic southern
      analysis using neo-gene probe. When tissues harvested from mice after intravenous
      injection of 4T1E/M3 cells were examined histologically, markedly enhanced bone
      marrow metastasis was observed; 77% of spines from 4T1E/M3-injected mouse showed
      metastasis as compared to 14% metastasis seen with the parent cells. In vitro,
      4T1E/M3 cells attached more strongly to the plastic plate and to bone marrow
      derived endothelial cells. DNA micro arrays, real time RT-PCR and FACS analyses
      revealed that the expression of ICAM-1 and beta2 integrin was upregulated in
      4T1E/M3 cells at both the mRNA and cell surface protein levels. 4T1E/M3 cells
      also showed greater anchorage-independent proliferation in soft agar, and
      migrated markedly faster than the parent cells in wound healing assays. Anti-ICAM
      1 antibodies strongly inhibited both the colony formation and the migration
      activity of 4T1E/M3 suggesting the importance of the role of ICAM-1. Our newly
      established highly metastatic 4T1E/M3 cells may provide a potentially powerful
      tool to study the molecular mechanisms of bone marrow metastasis and to identify
      new molecular targets for therapeutic interventions.

PMID- 18340425
TI  - Decreased adhesiveness, resistance to anoikis and suppression of GRP94 are
      integral to the survival of circulating tumor cells in prostate cancer.
AB  - The presence of circulating tumor cells (CTC) is common in prostate cancer
      patients, however until recently their clinical significance was unknown. The CTC
      stage is essential for the formation of distant metastases, and their continuing
      presence after radical prostatectomy has been shown to predict recurrent or
      latent disease. Despite their mechanistic and prognostic importance, due both to
      their scarcity and difficulties in their isolation, little is known about the
      characteristics that enable their production and survival. The aim of this study
      was to investigate the molecular mechanisms underlying the survival of CTC cells.
      A novel CTC cell line from the bloodstream of an orthotopic mouse model of
      castration-resistant prostate cancer was established and compared with the
      primary tumor using attachment assays, detachment culture, Western blot, flow
      cytometry and 2D gel electrophoresis. Decreased adhesiveness and expression of
      adhesion molecules E-cadherin, beta4-integrin and gamma-catenin, together with
      resistance to detachment and drug-induced apoptosis and upregulation of Bcl-2
      were integral to the development of CTC and their survival. Using proteomic
      studies, we observed that the GRP94 glycoprotein was suppressed in CTC. GRP94 was
      also shown to be suppressed in a tissue microarray study of 79 prostate cancer
      patients, indicating its possible role in prostate cancer progression. Overall,
      this study suggests molecular alterations accounting for the release and survival
      of CTC, which may be used as drug targets for either anti-metastatic therapy or
      the suppression of latent disease. We also indicate the novel involvement of
      GRP94 suppression in prostate cancer metastasis.

PMID- 18340426
TI  - [New data and recommendations of antiviral therapy of chronic hepatitis B and C].
AB  - According to the new German guidelines therapy of chronic hepatitis B is
      recommended when HBV-DNA is >10.000 copies/ml and when GPT is >twice the ULN or
      biopsy shows inflammation/fibrosis. When patients are not suitable for interferon
      therapy, mono-therapy with adefovir, entecavir, telbivudine of lamivudine may be
      initiated provided that HBV-DNA is <1 Mio. copies/ml and cirrhosis is absent.
      When viral load is high, entecavir should be preferred. HBV-DNA need to be
      checked for early detection of non-response or resistance. When resistance is
      present, combination therapy is recommended.New studies warrant individualization
      of previous recommendation for therapy of hepatitis C because one can now early
      evaluate how successful and long the therapy shall be. When viral load is low and
      HCV-RNA becomes negative after 4 weeks, therapy may be shortened to 24 weeks.
      Without such rapid response HCV-RNA needs to be checked after 12 and 24 weeks:
      when HCV-RNA becomes negative only after 24 weeks, a prolongation of therapy
      might be advisable.

PMID- 18340429
TI  - [Robot-assisted (da Vinci) laparoscopy: the beginning of a new era in operative
      urology?].
AB  - The da Vinci Surgical System represents a new technology in advanced laparoscopy:
      Sitting at a console that allows three-dimensional vision of the operating field,
      the robotic surgeon is enabled to perform complex laparoscopic procedures. The
      movements of telemanipulators ("masters") are transferred to EndoWrist
      instruments with all degrees of freedom. Compared with conventional laproscopy,
      the technology allows more dexterity, a shorter learning curve, improved vision,
      reduced operating time with reduced staff requirements, and an ergonomically
      designed work station with minimal burden on the back and joints. The following
      article describes the principles of this technology and the challenges of the
      capital investment and the running costs.

PMID- 18340430
TI  - Studies of regional adipose transplantation reveal a unique and beneficial
      interaction between subcutaneous adipose tissue and the intra-abdominal
      compartment.

PMID- 18340431
TI  - Glucose lowers the threshold for human aortic vascular smooth muscle cell
      migration: inhibition by protein phosphatase-2A.
AB  - AIMS/HYPOTHESIS: Atherosclerosis, which occurs prematurely in individuals with
      diabetes, incorporates vascular smooth muscle cell (VSMC) chemotaxis. Glucose,
      through protein kinase C-beta(II) signalling, increases chemotaxis to low
      concentrations of platelet-derived growth factor (PDGF)-BB. In VSMC, a biphasic
      response in PDGF-beta receptor (PDGF-betaR) level occurs as PDGF-BB
      concentrations increase. The purpose of this study was to determine whether
      increased concentrations of PDGF-BB and raised glucose level had a modulatory
      effect on the mitogen-activated protein kinase/extracellular-regulated protein
      kinase pathway, control of PDGF-betaR level and chemotaxis. METHODS: Cultured
      aortic VSMC, exposed to normal glucose (NG) (5 mmol/l) or high glucose (HG) (25
      mmol/l) in the presence of PDGF-BB, were assessed for migration (chemotaxis
      chamber) or else extracted and immunoblotted. RESULTS: At concentrations of PDGF
      BB <540 pmol/l, HG caused an increase in the level of PDGF-betaR in VSMC
      (immunoblotting) versus NG, an effect that was abrogated by inhibition of aldose
      reductase or protein kinase C-beta(II). At higher concentrations of PDGF-BB (>540
      pmol/l) in HG, receptor level was reduced but in the presence of aldose reductase
      or protein kinase C-beta(II) inhibitors the receptor levels increased. It is
      known that phosphatases may be activated at high concentrations of growth
      factors. At high concentrations of PDGF-BB, the protein phosphatase (PP)2A
      inhibitor, endothall, caused an increase in PDGF-betaR levels and a loss of
      biphasicity in receptor levels in HG. At higher concentrations of PDGF-BB in HG,
      the chemoattractant effect of PDGF-BB was lost (chemotaxis chamber). Under these
      conditions inhibition of PP2A was associated with a restoration of chemotaxis to
      high concentrations of PDGF-BB. CONCLUSION/INTERPRETATION: The biphasic response
      in PDGF-betaR level and in chemotaxis to PDGF-BB in HG is due to PP2A activation.

PMID- 18340432
TI  - [Revision surgery after implantation of a vertebral disc prosthesis].
AB  - Assessment of the revisability of surgery after the endoprosthetic replacement of
      vertebral discs shows that the surgical approach depends on the time of revision
      surgery and the reason why it is carried out. Our experience is based on nine
      revision operations out of 152 cervical vertebra prostheses of the Bryan and
      Prodisc C types implanted from 2003 to 2007 and 312 endoprostheses of the Charite
      and Prodisc types implanted from 1999 to 2007. Our own results show differing
      approaches in perioperative or late postoperative revision operations. Operations
      to exchange implants were not possible, whereas a change of surgical procedure is
      the rule. The same access route can usually be selected in the cervical spine,
      but in the lumbar spine this can only be done perioperatively; if revision
      surgery is carried out at a later date, an alternative access route must be used.
      Using strict indications for the primary implant is the only way to prevent
      postoperative revision surgery that is due to an inaccurate primary assessment
      and not to the vertebral endoprosthesis (e.g. post-discotomy syndrome, facet
      joint arthropathy, rotation instability, vertebral slip). The next generation of
      vertebral disc endoprostheses must incorporate reduced load of the zygapophyseal
      joints and improved revisability.

PMID- 18340433
TI  - [Balloon kyphoplasty for recent vertebral fractures in the elderly].
AB  - BACKGROUND: An increasing life expectancy is often accompanied by a possible
      increase of vertebral fractures. If operative therapy is necessary, open
      procedures might be problematic for elderly patients. In this case, balloon
      kyphoplasty might be an alternative. METHODS: We present our prospective data of
      30 patients with an average age of 72 years (range 65-82). The patients suffered
      from isolated thoracic and lumbar fractures (T6-L4) without neurological deficits
      and were operated on with balloon kyphoplasty. They were followed up an average
      of 13 months after surgery. RESULTS: Before surgery, the patients' average
      kyphotic angle was 12 degrees . After reduction with balloon kyphoplasty, this
      angle was significantly improved to 7 degrees , and at follow-up it was 8 degrees
      . Back pain, which was determined by a visual analogous scale, showed a
      significant reduction from 8.2 to 2.6 points at follow-up. No significant
      relationship between preoperative pain and improvement of the kyphotic angle
      could be found. Patients with a bad fracture reposition showed significantly more
      pain at follow-up. However, there was no difference between the reference group
      and the examined patients' quality of life regarding general health. CONCLUSION:
      Recent fractures of the thoracic or lumbar spine in elderly patients treated by
      balloon kyphoplasty showed good early results.

PMID- 18340435
TI  - DNA linearization through confinement in nanofluidic channels.
AB  - Stretching DNA has emerged as a vital process for studying the physical and
      biological properties of these molecules. Over the past decade, there has been
      increasing research interest in utilizing nanoscale fluidic channels to confine
      and stretch single DNA molecules. Nanofabricated systems for linearizing DNA have
      revealed new and important insights into the conformation changes of DNA
      molecules. They also have emerged as innovative techniques for efficiently
      separating DNA molecules based on size and for physically mapping genetic
      information along the genome. This review describes physical theories of DNA
      linearization, current DNA stretching techniques based on nanofabricated
      channels, and breakthroughs resulting from the use of nanofluidic channels for
      DNA linearization.

PMID- 18340436
TI  - Fluorescence detection techniques for protein kinase assay.
AB  - Traditional methods for protein kinase (PK) assay are mainly based on use of
      (32)P-labeled adenosine triphosphate (ATP); applications of such methods are,
      however, hampered by radioactive waste and short half-life of (32)P-labeled ATP.
      Therefore non-radioactive methods, such as fluorescence detection techniques are
      good alternative. In this review, we describe the principles of four fluorescence
      techniques (fluorescence intensity endpoint measurement, fluorescence resonance
      energy transfer (FRET), fluorescence polarization (FP), and fluorescence lifetime
      imaging) and provide an overview of applications of these fluorescence detection
      techniques in protein kinase assay, underlining their relative advantages and
      limitations. Research trends in this field are also highlighted. [figure: see
      text]

PMID- 18340437
TI  - Investigating morphological changes in treated vs. untreated stone building
      materials by x-ray micro-CT.
AB  - Calcareous stones have been largely used to build historical buildings. Among
      these, the calcarenites are usually characterized by a high content of calcite
      and a high open porosity, which make them very sensitive to the weathering caused
      by physical and chemical agents. In order to prevent their deterioration and to
      retard their decay, different protective products-mainly polymers-are applied on
      the stone artefact surfaces. In this work we apply the methodology tested in a
      preliminary study to investigate the morphological changes of the internal
      structure of a biocalcarenite (Lecce stone) by micro x-ray computed tomography
      (micro-CT). The porosity and other morphological parameters of the rock before
      and after the conservation treatment were calculated on a significant number of
      samples. The Student's t test was applied for statistical comparison. The results
      reveal that the treatment with Paraloid B72 (PB 72) is homogenously distributed
      and causes small changes to the natural properties of the rock, whereas the
      application of a fluoroelastomer (NH) causes an appreciable decrease in porosity
      and variation in terms of wall thickness distribution, probably resulting from
      its inhomogeneous distribution.

PMID- 18340438
TI  - Speed-related spinal excitation from ankle dorsiflexors to knee extensors during
      human walking.
AB  - Automatic adjustments of muscle activity throughout the body are required for the
      maintenance of balance during human walking. One mechanism that is likely to
      contribute to this control is the heteronymous spinal excitation between human
      ankle dorsiflexors and knee extensors (CPQ-reflex). Here, we investigated the CPQ
      reflex at different walking speeds (1-6 km/h) and stride frequencies (0.6-1.3 Hz)
      in healthy human subjects to provide further evidence of its modulation, and its
      role in ensuring postural stability during walking. The CPQ-reflex was small or
      absent at walking speeds below 2-3 km/h, then increased with walking speeds about
      3-4 km/h, and reached a plateau without any further change at walking speeds from
      4 to 6 km/h. The reflex showed no modulation when the stride cycle was varied at
      constant speed (4 km/h; short steps versus long steps). These changes were
      unlikely to be only caused by changes in the background EMG activity and
      modifications in peripheral input, and likely reflected central modulation of
      transmission in the involved reflex pathways as well. It is suggested that the
      purpose of the reflex is to ensure knee stability at moderate-to-high walking
      speeds.

PMID- 18340439
TI  - Neuropsychology of self-awareness in young adults.
AB  - Disorders of self-awareness are common following cortical damage, particularly to
      the frontal lobes, but there have been few studies of individual differences in
      self-awareness in the normal population. In the current study, we explored
      patterns of metacognitive awareness among healthy young adults, based on
      discrepancies of self- and other-ratings on the Frontal Systems Behavior Scale
      (FrSBe; Grace and Malloy, 2002). Those who showed poor metacognitive awareness
      showed more frequent lapses of attention, and higher levels of everyday
      absentmindedness, than those who accurately appraised their own behavior or those
      who overestimated their own FrSBe scores. Furthermore, among those with poor
      metacognitive awareness, online emergent awareness correlated positively with
      prospective memory performance, and negatively with anxiety scores. Our results
      suggest that accurate self-awareness in non-neurological participants relies on
      efficient sustained attention functioning, supporting the role of frontal control
      systems in neuroanatomical models of self-awareness.

PMID- 18340440
TI  - Interactions between auditory and somatosensory feedback for voice F0 control.
AB  - Previous studies have demonstrated the importance of both kinesthetic and
      auditory feedback for control of voice fundamental frequency (F0). In the present
      study, a possible interaction between auditory feedback and kinesthetic feedback
      for control of voice F0 was tested by administering local anesthetic to the vocal
      folds in the presence of perturbations in voice pitch feedback. Responses to
      pitch-shifted voice feedback were larger when the vocal fold mucosa was
      anesthetized than during normal kinesthesia. A mathematical model incorporating a
      linear combination of kinesthesia and pitch feedback simulated the main aspects
      of our experimental results. This model indicates that a feasible explanation for
      the increase in response magnitude with vocal fold anesthesia is that the vocal
      motor system uses both pitch and kinesthesia to stabilize voice F0 shortly after
      a perturbation of voice pitch feedback has been perceived.

PMID- 18340441
TI  - Solvent effects on fluorescence properties of protochlorophyll and its
      derivatives with various porphyrin side chains.
AB  - Fluorescence spectra and fluorescence lifetimes of protochlorophyll (Pchl) were
      measured in organic solvents having different physical and chemical properties
      and were analyzed taking into account the nonspecific (dependent on bulk solvent
      parameters), and specific (e.g. H bonds, Mg coordination) solvent-solute
      interactions. The energy of the fluorescence emission band decreased, while the
      Stokes shift increased for increasing solvent orientation polarizability, which
      is a function of both the dielectric constant (epsilon) and the refractive index
      (n). The extent of the dependence of the Stokes shift on solvent orientation
      polarizability was higher in protic (i.e. those able to form hydrogen-binding)
      than in aprotic solvents. High value of the Stokes shift was also observed in
      pyridine and methanol, i.e. in solvents hexacoordinating the central Mg atom. The
      fluorescence decay of Pchl was monoexponential in all of the investigated
      solvents. The fluorescence lifetime decreased for increasing solvent orientation
      polarizability from 5.5 +/- 0.1 ns in 1,4-dioxane to 3.3 +/- 0.1 ns in methanol.
      Longer lifetime values were observed in the case of aprotic solvents than in
      protic solvents. The hexacoordination of Mg had no effect on the fluorescence
      lifetime. The present data are discussed with respect to results found for
      protochlorophyllide (Pchlide) (Mysliwa-Kurdziel et al. in Photochem Photobiol
      79:62-67, 2004), and they indicate that the presence of phytol chain in the
      porphyrin ring influences the spectral properties of the whole chromophore. This
      is the first complex analysis comparing the fluorescence emission and
      fluorescence lifetimes of purified Pchl and Pchlide.

PMID- 18340442
TI  - From genome sequence to integrated bioprocess for succinic acid production by
      Mannheimia succiniciproducens.
AB  - Mannheimia succiniciproducens is a capnophilic gram-negative bacterium isolated
      from bovine rumen. Wild-type M. succiniciproducens can produce succinic acid as a
      major fermentation product with acetic, formic, and lactic acids as byproducts
      during the anaerobic cultivation using several different carbon sources. Succinic
      acid is an important C4 building block chemical for many applications. Here, we
      review the progress made with M. succiniciproducens for efficient succinic acid
      production; the approaches taken towards the development of an integrated process
      for succinic acid production are described, which include strain isolation and
      characterization, complete genome sequencing and annotation, development of
      genetic tools for metabolic engineering, strain development by systems approach
      of integrating omics and in silico metabolic analysis, and development of
      fermentation and recovery processes. We also describe our current effort on
      further improving the performance of M. succiniciproducens and optimizing the mid
      and downstream processes. Finally, we finish this mini-review by discussing the
      issues that need to be addressed to make this process of fermentative succinic
      acid production employing M. succiniciproducens to reach the industrial-scale
      process.

PMID- 18340443
TI  - Fertilizer-dependent efficiency of Pseudomonads for improving growth, yield, and
      nutrient use efficiency of wheat (Triticum aestivum L.).
AB  - Acquisition of nutrients by plants is primarily dependent on root growth and
      bioavailability of nutrients in the rooting medium. Most of the beneficial
      bacteria enhance root growth, but their effectiveness could be influenced by the
      nutrient status around the roots. In this study, two 1-aminocyclopropane-1
      carboxylate (ACC)-deaminase containing plant-growth-promoting rhizobacteria
      (PGPR), Pseudomonas fluorescens and P. fluorescens biotype F were tested for
      their effect on growth, yield, and nutrient use efficiency of wheat under
      simultaneously varying levels of all the three major nutrients N, P, and K (at
      0%, 25%, 50%, 75%, and 100% of recommended doses). Results of pot and field
      trials revealed that the efficacy of these strains for improving growth and yield
      of wheat reduced with the increasing rates of NPK added to the soil. In most of
      the cases, significant negative linear correlations were recorded between
      percentage increases in growth and yield parameters of wheat caused by
      inoculation and increasing levels of applied NPK fertilizers. It is highly likely
      that under low fertilizer application, the ACC-deaminase activity of PGPR might
      have caused reduction in the synthesis of stress (nutrient)-induced inhibitory
      levels of ethylene in the roots through ACC hydrolysis into NH(3) and alpha
      ketobutyrate. The results of this study imply that these Pseudomonads could be
      employed in combination with appropriate doses of fertilizers for better plant
      growth and savings of fertilizers.

PMID- 18340444
TI  - Enhancing thermostability of Escherichia coli phytase AppA2 by error-prone PCR.
AB  - Phytases are used to improve phosphorus nutrition of food animals and reduce
      their phosphorus excretion to the environment. Due to favorable properties,
      Escherichia coli AppA2 phytase is of particular interest for biotechnological
      applications. Directed evolution was applied in the present study to improve
      AppA2 phytase thermostability for lowering its heat inactivation during feed
      pelleting (60-80 degrees C). After a mutant library of AppA2 was generated by
      error-prone polymerase chain reaction, variants were expressed initially in
      Saccharomyces cerevisiae for screening and then in Pichia pastoris for
      characterizing thermostability. Compared with the wild-type enzyme, two variants
      (K46E and K65E/K97M/S209G) showed over 20% improvement in thermostability (80
      degrees C for 10 min), and 6-7 degrees C increases in melting temperatures (T
      (m)). Structural predictions suggest that substitutions of K46E and K65E might
      introduce additional hydrogen bonds with adjacent residues, improving the enzyme
      thermostability by stabilizing local interactions. Overall catalytic efficiency
      (k (cat) / K (m)) of K46E and K65E/K97M/S209G was improved by 56% and 152% than
      that of wild type at pH 3.5, respectively. Thus, the catalytic efficiency of
      these enzymes was not inversely related to their thermostability.

PMID- 18340445
TI  - Isoflavone aglycones production from isoflavone glycosides by display of beta
      glucosidase from Aspergillus oryzae on yeast cell surface.
AB  - For efficient production of isoflavone aglycones from soybean isoflavones, we
      isolated three novel types of beta-glucosidase (BGL1, BGL3, and BGL5) from the
      filamentous fungi Aspergillus oryzae. Three enzymes were independently displayed
      on the cell surface of a yeast Saccharomyces cerevisiae as a fusion protein with
      alpha-agglutinin. Three beta-glucosidase-displaying yeast strains hydrolyzed
      isoflavone glycosides efficiently but exhibited different substrate
      specificities. Among these beta-glucosidases, BGL1 exhibited the highest activity
      and also broad substrate specificity to isoflavone glycosides. Although glucose
      released from isoflavone glycosides are generally known to inhibit beta
      glucosidase, the residual ratio of isoflavone glycosides in the reaction mixture
      with BGL1-displaying yeast strain (Sc-BGL1) reached approximately 6.2%, and the
      glucose concentration in the reaction mixture was maintained at lower level. This
      result indicated that Sc-BGL1 assimilated the glucose before they inhibited the
      hydrolysis reaction, and efficient production of isoflavone aglycones was
      achieved by engineered yeast cells displaying beta-glucosidase.

PMID- 18340446
TI  - Toxins from cone snails: properties, applications and biotechnological
      production.
AB  - Cone snails are marine predators that use venoms to immobilize their prey. The
      venoms of these mollusks contain a cocktail of peptides that mainly target
      different voltage- and ligand-gated ion channels. Typically, conopeptides consist
      of ten to 30 amino acids but conopeptides with more than 60 amino acids have also
      been described. Due to their extraordinary pharmacological properties,
      conopeptides gained increasing interest in recent years. There are several
      conopeptides used in clinical trials and one peptide has received approval for
      the treatment of pain. Accordingly, there is an increasing need for the
      production of these peptides. So far, most individual conopeptides are
      synthesized using solid phase peptide synthesis. Here, we describe that at least
      some of these peptides can be obtained using prokaryotic or eukaryotic expression
      systems. This opens the possibility for biotechnological production of also
      larger amounts of long chain conopeptides for the use of these peptides in
      research and medical applications.

PMID- 18340447
TI  - Immunological mechanisms in the pathogenesis of diabetic retinopathy.
AB  - There is an accumulating body of evidence that immunological mechanisms play a
      prominent role in the pathogenesis of diabetic retinopathy (DR), which is
      characterized by many features typical of inflammation. The upregulation of
      cytokines and other inflammatory mediators leading to persistent low-grade
      inflammation and an influx of leukocytes, is believed to contribute actively to
      DR-associated damage to the retinal vasculature and retinal neovascularization.
      This review will describe preclinical and clinical studies that document an
      inflammatory basis for DR and that support the use of nonsteroidal anti
      inflammatory drugs, corticosteroids, and anti-vascular endothelial growth factor
      agents in its treatment. In addition, emerging therapeutic approaches based on
      ongoing investigations will be discussed, including those involving blockade of
      angiotensin receptors and other molecular targets such as tumor necrosis factor
      alpha.

PMID- 18340448
TI  - [Odontogenic tumors and cysts of the jaw].

PMID- 18340450
TI  - Ultrastructure and histochemical analysis of extracellular matrix surface network
      in kiwifruit endosperm-derived callus culture.
AB  - The study used Actinidia deliciosa endosperm-derived callus to investigate
      aspects of the morphology, histology and chemistry of extracellular matrix (ECM)
      structures in morphogenically stable tissue from long-term culture. SEM showed
      ECM as a membranous layer or reticulated fibrillar and granular structure linking
      the peripheral cells of callus domains. TEM confirmed that ECM is a distinct
      heterogeneous layer, up to 4 mum thick and consisting of amorphous dark-staining
      material, osmiophilic granules and reticulated fibres present outside the outer
      callus cell wall. ECM covered the surface of cells forming morphogenic domains
      and was reduced during organ growth. This structure may be linked to acquisition
      of morphogenic competence and thus may serve as a structural marker of it in
      endosperm-derived callus. ECM was also observed on senescent cells in contact
      with the morphogenic area. Treatment of living calluses with chloroform and
      washing with ether-methanol led to partial destruction of the extracellular
      layer. Digestion with pectinase removed the membranous layer almost completely
      and exposed thick fibrillar strands and granular remnants. Digestion with
      protease did not visibly affect the surface layer. Indirect immunofluorescence
      showed low-methylesterified pectic epitopes labelled by JIM5 monoclonal antibody.
      Immunolabelling, histochemistry, and solvent and enzyme treatments suggested
      pectins and lipids as components of the surface layer. These compounds may
      indicate protective, water retention and/or cell communication functions for this
      external layer.

PMID- 18340449
TI  - Chondroprotective effects of glucosamine involving the p38 MAPK and Akt signaling
      pathways.
AB  - The purpose of the present study was to elucidate the possible signal
      transduction pathway involved in the underlying mechanism of glucosamine (GLN)'s
      influence on the gene expression of matrix metalloproteinases (MMPs) in
      chondrocytes stimulated with IL-1beta. Using chondrosarcoma cells stimulated with
      IL-1beta, the effects of GLN on the mRNA and protein levels of MMP-3, the
      activation of JNK, ERK, p38, NF-kappaB, and AP-1, the nuclear translocation of NF
      kappaB/Rel family members, and PI3-kinase/Akt activation were studied. GLN
      inhibited the expression and the synthesis of MMP-3 induced by IL-1beta, and that
      inhibition was mediated at the level of transcription involving both the NF
      kappaB and AP-1 transcription factors. Translocation of NF-kappaB was reduced by
      GLN as a result of the inhibition of IkappaB degradation. A slightly synergistic
      effect on the activation of AP-1 induced by IL-1beta was shown in the presence of
      GLN. Among MAPK pathways involved in the transcriptional regulation of AP-1,
      phosphorylation of JNK and ERK was found to increase with the presence of GLN
      under IL-1beta treatment, while that for p38 decreased. It was also found that
      GLN alone, but also synergistically with IL-1beta, was able to activate the Akt
      pathway. The requirements of NF-kappaB translocation and p38 activity are
      indispensably involved in the induction of MMP-3 expression in chondrosarcoma
      cells stimulated by IL-1beta. Inhibition of the p38 pathway in the presence of
      GLN substantially explains the chondroprotective effect of GLN on chondrocytes
      that regulate COX-2 expression, PGE(2) synthesis, and NO expression and
      synthesis. The chondroprotective effect of GLN through the decrease in MMP-3
      production and stimulation of proteoglycan synthesis may follow another potential
      signaling pathway of Akt.

PMID- 18340451
TI  - Immunolocalization of cholesterol side chain cleavage enzyme (P450scc) in Mytilus
      galloprovincialis and its induction by nutritional levels.
AB  - We have examined the localization of P450scc in different tissues of the mollusc
      Mytilus galloprovincialis along a gonadal cycle by using a polyclonal antibody
      against rat cholesterol side-chain cleavage enzyme (cytochrome P450scc).
      Immunoreactivity specific for P450scc was found only in the cytoplasm of
      basophilic cells from digestive gland; gonad, gills and kidney appeared to be
      devoid of P450scc immunoreactivity. SDS-gel electrophoresis and western blot
      analysis of different subcellular fractions revealed that this protein is mainly
      located in microsomes, has a molecular weight of 51.4 kDa and is recognized by
      the antibody against rat P450scc. These results suggest that the digestive gland
      of M. galloprovincialis could be considered a steroidogenic tissue where the
      first step in biosynthesis of steroid hormones occurs. Moreover, seasonal slot
      blot analysis of post-mitochondrial fractions showed a P450scc induction by
      available nutrients and phytoplankton blooms.

PMID- 18340452
TI  - Colorectal cancer progression correlates with upregulation of S100A11 expression
      in tumor tissues.
AB  - BACKGROUND AND AIMS: Early detection and treatment of human colorectal cancers
      remain a challenge. Identification of new potential markers may help in the
      diagnosis of colorectal cancer. MATERIALS AND METHODS: By comparative two
      dimensional gel electrophoresis using extracts from colorectal tumor and adjacent
      normal tissues, we identified a calcium-binding protein, S100A11, which was
      highly expressed in colorectal cancer compared with adjacent normal tissues. We
      expanded our study in 89 clinical colorectal tumor samples to validate this
      finding and correlates S100A11 expression in human colorectal cancer tissues with
      various stages of the tumor by Western blotting and immunohistochemical staining.
      RESULTS: We identified a calcium-binding protein, S100A11, which was highly
      expressed in colorectal cancer compared with adjacent normal tissues. S100A
      protein was expressed predominantly in the cytoplasm of normal tissue; however,
      it was expressed in both the nuclei and cytoplasm of colorectal cancer. S100A11
      level in colorectal cancer tissue was increased following stage progression of
      the disease. CONCLUSION: These findings suggest S100A11 could be helpful in the
      pathological study of colorectal cancer, especially for the classification of
      different stages in colorectal cancer.

PMID- 18340453
TI  - Survivin expressions in human hepatoma HepG2 cells exposed to ionizing radiation
      of different LET.
AB  - Survivin is a member of the inhibitors of apoptosis (IAP) protein family that
      interferes with post-mitochondrial events including activation of caspases. To
      examine the regulation of survivin expression in response to irradiation with
      different linear energy transfer (LET), human hepatoma HepG2 cells were
      irradiated in vitro with X-rays and carbon ions. Cellular sensitivities to low-
      and high-LET radiation were determined by colony formation. Survivin expression
      at mRNA and protein level were measured with RT-PCR and Western blot analyses,
      respectively. Radiation-induced cell cycle arrest and apoptosis were investigated
      with flow cytometry. We found that low-LET X-rays induced dose-dependent
      increases in survivin expression. After exposure to high-LET carbon ions,
      survivin expression gradually increased from 0 to 4 Gy, and then declined at 6
      Gy. More pronounced survivin expression, stronger G(2)/M phase arrest was
      observed after exposure to carbon ions in comparison with X-rays at doses from 0
      to 4 Gy. These observations indicate that there is a differential survivin
      expression in response to different LET radiations and the cycle arrest mechanism
      may be associated with it. In addition, our data on induction of apoptosis are
      compatible with the assumption that survivin expression induced by low-LET X-rays
      radiation may play a critical role in inhibiting apoptosis. However, after
      irradiation with ions, an anti-apoptotic function of survivin is not evident,
      possibly because of the serious damage produced by densely ionizing radiation.

PMID- 18340454
TI  - Epithelial and endothelial barriers in the olfactory region of the nasal cavity
      of the rat.
AB  - The olfactory ensheathing (glial) cells (OECs) have been identified to be useful
      candidate cells to support regeneration after being transplanted into injured
      fiber tracts of the central nervous system. We investigated by means of
      immunocytochemistry and freeze-fracturing the morphology and molecular
      composition of OEC tight junctions in the rat olfactory system. In addition, we
      tested the hypothesis whether tight junctions and orthogonal arrays of particles
      (OAPs) which contain the water channel protein aquaporin-4 (AQP4), are mutually
      exclusive as suggested in previous studies. In OECs, we found neither OAPs nor
      AQP4, but tight junctions immunoreactive for ZO-1, occludin, and claudin-5, but
      immunonegative for ZO-2 and claudin-3. To shed more light on the function of OEC
      tight junctions, we tested the permeability and tight junction composition of
      blood vessels and fila olfactoria. We found them both, permeable for infused
      lanthanum nitrate, and to be immunopositive for ZO-1 and claudin-5. The tight
      junctions of the OECs are discussed to be responsible for micro
      compartmentalization within the olfactory fiber tract providing a benefit for
      axonal growth.

PMID- 18340455
TI  - Role of muscle mass on sprint performance: gender differences? by Jorge Perez
      Gomez, German Vicente Rodriguez, Ignacio Ara, Hugo Olmedillas, Javier Chavarren,
      Juan Jose Gonzalez-Henriquez, Cecilia Dorado and Jose A. L. Calbet.

PMID- 18340456
TI  - Effects of concentric and repeated eccentric exercise on muscle damage and
      calpain-calpastatin gene expression in human skeletal muscle.
AB  - The purpose of this study was to compare the responsiveness of changes in Ca(2+)
      content and calpain-calpastatin gene expression to concentric and eccentric
      single-bout and repeated exercise. An exercise group (n = 14) performed two bouts
      of bench-stepping exercise with 8 weeks between exercise bouts, and was compared
      to a control-group (n = 6). Muscle strength and soreness and plasma creatine
      kinase and myoglobin were measured before and during 7 days following exercise
      bouts. Muscle biopsies were collected from m. vastus lateralis of both legs prior
      to and at 3, 24 h and 7 days after exercise and quantified for muscle Ca(2+)
      content and mRNA levels for calpain isoforms and calpastatin. Exercise reduced
      muscle strength and increased muscle soreness predominantly in the eccentric leg
      (P < 0.05). These responses as well as plasma levels of creatine kinase and
      myoglobin were all attenuated after the repeated eccentric exercise bout (P <
      0.05). Total muscle Ca(2+)-content did not differ between interventions. mRNA
      levels for calpain 2 and calpastatin were upregulated exclusively by eccentric
      exercise 24 h post-exercise (P < 0.05), with no alteration in expression between
      bouts. Calpain 1 and calpain 3 mRNA did not change at any specific time point
      post-exercise for either intervention. Our mRNA results suggest a regulation on
      the calpain-calpastatin expression response to muscle damaging eccentric
      exercise, but not concentric exercise. Although a repeated bout effect was
      demonstrated in terms of muscle function, no immediate support was provided to
      suggest that regulation of expression of specific system components is involved
      in the repeated bout adaptation.

PMID- 18340457
TI  - Energy cost and energy sources of a ballet dance exercise in female adolescents
      with different technical ability.
AB  - This study evaluated energy cost and energy sources of a ballet exercise (grand
      adage) in young female dancers with different technical ability, and then related
      the energy sources to the subject's VO(2max) and anaerobic threshold (IAT).
      Twenty-five dancers (13-16 years) were divided into two different technical
      ability groups: low-level (n = 13) and high-level (n = 12). The overall energy
      requirement of dance exercise (VO(2eq)) was obtained by adding the amount of
      VO(2) during exercise above resting (aerobic source or VO(2ex)) to the VO(2) up
      to the fast component of recovery (anaerobic alactic source or VO(2al)) and to
      the energy equivalent of peak blood lactate accumulation (anaerobic lactic source
      or VO(2la) of recovery. VO(2eq) of exercise amounted to 81 +/- 10 and 94 +/- 9 ml
      kg(-1) in low-level and high-level groups, respectively. VO(2ex) represented the
      higher fraction (65 +/- 4% and 77 +/- 5%) in low-level and high-level groups,
      respectively, of VO(2eq )in both the groups. In the low-level group the remaining
      fractions were: 23 +/- 2 % for VO(2al) and 12 +/- 1% for VO(2la). In high-level
      group the remaining fractions were: 18 +/- 2 % for VO(2al) and 4 +/- 1% for
      VO(2la). Between two groups, significant differences were found in VO(2ex )(P <
      0.01), VO(2al) (P < 0.01), and VO(2al )(P < 0.05). IAT was 55 and 60% of VO(2max)
      for low-level and high-level dancers, respectively. Low-level dancers performed
      more exercise above IAT than high-level. For these reasons, it should be better
      to define exercise intensity according to the IAT parameter and not only to
      VO(2max).

PMID- 18340458
TI  - NOTES--third generation surgery. Vain hopes or the reality of tomorrow?
AB  - BACKGROUND: Laparoscopic approach has made many procedures less invasive;
      however, it seems like this is not enough. The newest challenge for the medical
      environment is applying the scarless surgery in humans. In this article, we
      review the origin, current state of art, and future of natural orifice
      transluminal endoscopic surgery (NOTES). The registered base of research in
      humans is yet scarce; however, the porcine model experimental studies hold a
      great promise. In NOTES, peritoneal cavity can be easily achieved, and some
      procedures are feasible through the natural orifices like digestive tract,
      vagina, or urinary bladder. If safety and advantages of these approaches will be
      proven beyond question, NOTES procedures are likely to be adapted in humans after
      overcoming the critical obstacles, like reliable closure methods, indispensable
      equipment invention, the multidisciplinary specialists training, etc. The aim of
      this article was to review available literature to provide current state of art
      in NOTES surgery. MATERIALS AND METHODS: Medical databases were searched for
      animal and human experience with NOTES to give an overview of history, current
      state of art, and future of this technique. RESULTS: NOTES is currently the
      subject of the intensive research. It seems like this is only the matter of time
      when a transluminal access to the abdominal or even thoracic cavity will become
      the reality. Moreover, this will enable the management of some diseases in a
      possibly minimally invasive pattern, nearly painless and leaving no scar at all.

PMID- 18340459
TI  - Involvement of polyamines in the post-anthesis development of inferior and
      superior spikelets in rice.
AB  - Early-flowered superior spikelets usually exhibit a faster grain filling rate and
      heavier grain weight than late-flowered inferior spikelets in rice (Oryza sativa
      L.). But the intrinsic factors responsible for the variations between the two
      types of spikelets are unclear. This study investigated whether and how
      polyamines (PAs) are involved in regulating post-anthesis development of rice
      spikelets. Six rice genotypes differing in grain filling rate were field grown,
      and PA levels and activities of the enzymes involved in PA biosynthesis were
      measured in both superior and inferior spikelets. The results showed that
      superior spikelets exhibited higher levels of free spermidine (Spd) and free
      spermine (Spm) and higher activities of arginine decarboxylase (ADC, EC
      4.1.1.19), S-adenosylmethionine decarboxylase (SAMDC, EC 4.1.1.50) and Spd
      synthase (EC 2.5.1.16) than inferior spikelets at the early endosperm cell
      division and grain filling stage. The maximum concentrations of free Spd and free
      Spm and the maximum activities of ADC, SAMDC and Spd synthase were significantly
      correlated with the maximum cell division and grain filling rates, maximum cell
      number and grain weight. Application of Spd and Spm to panicles resulted in
      significantly higher rates of endosperm cell division and grain filling in
      inferior spikelets along with the activities of sucrose synthase (EC 2.4.1.13),
      ADP glucose pyrophosphorylase (EC 2.7.7.27) and soluble starch synthase (EC
      2.4.1.21), suggesting that these PAs are involved in the sucrose-starch metabolic
      pathway. The results indicate that the poor development of inferior spikelets is
      attributed, at least partly, to the low PA level and its low biosynthetic
      activity.

PMID- 18340460
TI  - Ultrastructural analysis of prefrontal cortical inputs to the rat amygdala:
      spatial relationships to presumed dopamine axons and D1 and D2 receptors.
AB  - Projections from the prefrontal cortex (PFC) to the amygdala (AMG) regulate
      affective behaviors in a manner that is modulated by dopamine (DA). Although PFC
      and DA inputs overlap within the basolateral nucleus (BLA) and intercalated cell
      masses (ICMs), the spatial relationship between these afferents has not been
      investigated, nor is it known how DA D1 (D1R) and D2 (D2R) receptors are
      localized in relationship to PFC terminals. We therefore combined tract-tracing
      from the rat PFC to the AMG with immunocytochemical labeling of tyrosine
      hydroxylase (TH) to identify presumed DA axons or D1R and D2R. In both the ICMs
      and BLA, PFC terminals formed asymmetric synapses onto spines that typically did
      not receive secondary synaptic inputs. TH-immunoreactive (-ir) fibers in the
      adjacent neuropil typically contacted different structures. Although PFC and TH
      ir axons were sometimes apposed to the same dendrites or to each other, PFC
      terminals only rarely synapsed onto dendrites that also received synapses from TH
      ir axons. D1R-ir spines and dendrites were observed commonly within the ICMs but
      less frequently within the BLA, and PFC axons in the ICMs occasionally synapsed
      onto D1R-ir spines. Within both regions, D2R-ir spines, dendrites, and axons were
      observed. PFC terminals occasionally contained presynaptic labeling for D2R but
      were not observed to synapse onto D2R-ir targets. The infrequent observation of
      synaptic convergence between PFC and presumed DA terminals within the AMG
      suggests that DA modulates PFC inputs primarily via extrasynaptic mechanisms, a
      conclusion supported by the localization of D2R within and D1R postsynaptic to
      PFC terminals.

PMID- 18340461
TI  - Epitope-specific in vivo protection against cytomegalovirus disease by CD8 T
      cells in the murine model of preemptive immunotherapy.
AB  - Preclinical research in murine models as well as subsequent clinical trials have
      concordantly revealed a high protective potential of antiviral CD8 T cells, of
      donor-derived ex vivo memory CD8 T cells in particular, in the immunotherapy of
      cytomegalovirus (CMV) infection in immunocompromised recipients. Although it is
      generally held view that the observed beneficial effect of the transferred cells
      is viral epitope-specific, involving the recognition of MHC class-I presented
      peptides by cognate T cell receptors, this assumption awaits formal proof, at
      least with regard to the in vivo function of the CD8 T cells. This question is
      particularly evident for CMV, since the function of viral immune evasion proteins
      interferes with the MHC class-I pathway of peptide presentation. Alternatively,
      therefore, one has to consider the possibility that the requirement for epitope
      recognition may be bypassed by other ligand-receptor interactions between CD8 T
      cells and infected cells, which may trigger the signaling for effector functions.
      Clearly, such a mechanism might explain why CD8 T cells are so efficient in
      controlling CMV infection despite the expression of viral immune evasion
      proteins. Here we provide direct evidence for epitope-specificity of antiviral
      protection by employing a recombinant murine CMV (mCMV), namely the mutant virus
      mCMV-IE1-L176A, in which an immunodominant viral epitope of the regulatory
      immediate-early protein IE1 is functionally deleted by a point mutation replacing
      leucine with alanine at the C-terminal MHC anchor position of the antigenic
      peptide.

PMID- 18340462
TI  - Correlation of dendritic cell maturation and the formation of aggregates of poly
      ubiquitinated proteins in the cytosol.
AB  - Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs) in
      the immune system. Therefore, they are able to take up antigen by phagocytosis,
      macropinocytosis or endocytosis, process it in the cytosol and present it to
      naive T cells. It is known that presentation of the immunodominant influenza
      virus nucleoprotein-derived CTL epitope is delayed in bone marrow-derived DCs
      (BMDCs) compared to non-professional APCs. This delay coincided with the
      formation of transient aggregations of ubiquitinated proteins (DALIS, dendritic
      cell aggresome-like induced structures), which contain probably defective
      ribosomal products (DRiPs). DRiPs appear in the cytosol of maturing DCs and
      macrophages. Normally, DRiPs are degraded rapidly by proteasomes. However, their
      storage in DALIS delays their degradation. So, it is hypothesized that DALIS can
      function as antigen depots allowing DCs to coordinate maturation and antigen
      presentation during their migration to the lymph nodes. Upon inhibition of
      several pathways among the in signal transduction pathways of DCs, like the
      phosphatidylinositol 3-kinase (PI3-K) or the mammalian target of Rapamycin
      (mTOR), the cells show a rendered maturation profile. The formation of DALIS is
      inhibited in these cells which can be expected to influence antigen processing
      and presentation.

PMID- 18340463
TI  - Defining chronic diseases and health conditions in childhood (0-18 years of age):
      national consensus in the Netherlands.
AB  - A national consensus procedure was organised to define chronic diseases and
      health conditions in childhood. Based on (1) a systematic literature search on
      the definitions of chronic conditions in childhood and (2) a theoretical
      framework of determinants and indicators of health conditions, a definition of
      chronic conditions in childhood was proposed. This proposal was subsequently
      modified according to the comments received from 21 Dutch experts (clinicians,
      researchers and representatives of patient organisations) in two written
      consultation rounds and one national meeting, until consensus was reached.
      Consensus was attained on a definition consisting of four criteria: a disease or
      condition is considered to be a chronic condition in childhood if: (1) it occurs
      in children aged 0 up to 18 years; (2) the diagnosis is based on medical
      scientific knowledge and can be established using reproducible and valid methods
      or instruments according to professional standards; (3) it is not (yet) curable
      or, for mental health conditions, if it is highly resistant to treatment and (4)
      it has been present for longer than three months or it will, very probably, last
      longer than three months, or it has occurred three times or more during the past
      year and will probably reoccur. This definition was operationalised using the ICD
      10 classification of the World Health Organisation (WHO; International
      Statistical Classification of Diseases and Related Health Problems [ICD], 10th
      revision, Geneva, Switzerland, 1992). By this systematic and thorough procedure,
      national consensus on a comprehensive definition of chronic conditions in
      children which can be used for epidemiological research was reached.

PMID- 18340464
TI  - Larvicidal efficacy of five cucurbitaceous plant leaf extracts against mosquito
      species.
AB  - Larvicidal activity of crude hexane, ethyl acetate, petroleum ether, acetone, and
      methanol extracts of the leaf of five species of cucurbitaceous plants, Citrullus
      colocynthis, Coccinia indica, Cucumis sativus, Momordica charantia, and
      Trichosanthes anguina, were tested against the early fourth instar larvae of
      Aedes aegypti L. and Culex quinquefasciatus (Say) (Diptera: Culicidae). The
      larval mortality was observed after 24 h of exposure. All extracts showed
      moderate larvicidal effects; however, the highest larval mortality was found in
      petroleum ether extract of C. colocynthis, methanol extracts of C. indica, C.
      sativus, M. charantia, and acetone extract of T. anguina against the larvae of A.
      aegypti (LC50=74.57, 309.46, 492.73, 199.14, and 554.20 ppm) and against C.
      quinquefasciatus (LC50=88.24, 377.69, 623.80, 207.61, and 842.34 ppm),
      respectively. The petroleum ether extract of C. colocynthis and methanol extract
      of M. charantia were more effective than the other extracts. This is an ideal eco
      friendly approach for the control of the dengue vector, A. aegypti, and the
      lymphatic filariasis vector, C. quinquefasciatus.

PMID- 18340465
TI  - Spotted fever group Rickettsia in brown dog ticks Rhipicephalus sanguineus in
      southwestern Spain.
AB  - A total of 2,229 adults ticks (1,428 males and 801 females) belonging to the
      brown dog tick, Rhipicephalus sanguineus Latreille, 1806, collected from dogs in
      Seville province (Andalusia), distributed in 500 lots ranging from one to eight
      specimens per lot, were examined for the presence of rickettsiae by molecular
      techniques. Specific rickettsiae DNA were detected in 90 lots (18%) of ticks
      tested. Sequence analysis of amplicons revealed that R. sanguineus ticks were
      infected exclusively with Rickettsia massiliae (including the strain Bar-29). The
      results of this study extend the knowledge of the geographic distribution and
      prevalence of these spotted fever group (SFG) rickettsiae and indicate that at
      least two of them, with yet uncertain pathogenicity to humans, are present in
      brown dog ticks in south western Spain. Although Mediterranean spotted fever
      (MSF) is an endemic disease in Andalusia, Rickettsia conorii was not found,
      whereas R. massiliae, recently described as a pathogenic species, was highly
      prevalent in this area. Our data suggest that in Andalusia a number of MSF or MSF
      like cases attributed to R. conorii could have been actually caused by other SFG
      rickettsia present in R. sanguineus, particularly, R. massiliae.

PMID- 18340466
TI  - A new mechanism of dominance in hypophosphatasia: the mutated protein can disturb
      the cell localization of the wild-type protein.
AB  - The dominant negative effect of mutations is rare in metabolic diseases and its
      mechanism has not been studied much. Hypophosphatasia, a bone inherited metabolic
      disorder, is a good model because the disease can be dominantly transmitted. The
      gene product activity depends on a homodimeric configuration and many mutations
      have been reported in the ALPL gene responsible for the disease. Using CFP/YFP
      tagged-TNSALP plasmids, transfections in COS cells and confocal fluorescence
      analyses, we studied the point mutation G232V (c.746G>T). We showed that the
      G232V protein sequestrates some of the wild-type protein into the cells and
      prevents it from reaching the membrane where it plays its physiological role.

PMID- 18340467
TI  - Immunolocalization of aquaporins 1, 2 and 7 in rete testis, efferent ducts,
      epididymis and vas deferens of adult dog.
AB  - The transepithelial movement of water into the male reproductive tract is an
      essential process for normal male fertility. Protein water channels, referred to
      as aquaporins (AQPs), are involved in increasing the osmotic permeability of
      membranes. This study has examined the expression of AQP1, AQP2, and AQP7 in
      epithelial cells in adult dog efferent ducts, epididymis, and vas deferens.
      Samples of dog male reproductive tract comprising fragments of the testis,
      initial segment, caput, corpus and cauda epididymidis, and vas deferens were
      investigated by immunohistochemistry and Western blotting procedures to show the
      localization and distribution of the AQPs. AQP1 was noted in rete testis, in
      efferent ducts, and in vessels in the intertubular space, suggesting that AQP1
      participated in the absorption of the large amount of testicular fluid occurring
      characteristically in the efferent ducts. AQP2 expression was found in the rete
      testis, efferent ducts and epididymis, whereas AQP7 was expressed in the
      epithelium of the proximal regions of the epididymis and in the vas deferens.
      This is the first time that AQP2 and AQP7 have been observed in these regions of
      mammalian excurrent ducts, but their functional role in the dog male reproductive
      tract remains unknown. Investigations of AQP biology could be relevant for
      clinical studies of the male reproductive tract and to technologies for assisted
      procreation.

PMID- 18340468
TI  - Study of the potential spermatogonial stem cell compartment in dogfish testis,
      Scyliorhinus canicula L.
AB  - In the lesser-spotted dogfish (Scyliorhinus canicula), spermatogenesis takes
      place within spermatocysts made up of Sertoli cells associated with stage
      synchronized germ cells. As shown in testicular cross sections, cysts radiate in
      maturational order from the germinative area, where they are formed, to the
      opposite margin of the testis, where spermiation occurs. In the germinative zone,
      which is located in a specific area between the tunica albuginea of the testis
      and the dorsal testicular vessel, individual large spermatogonia are surrounded
      by elongated somatic cells. The aim of this study has been to define whether
      these spermatogonia share characteristics with spermatogonial stem cells
      described in vertebrate and non-vertebrate species. We have studied their
      ultrastructure and their mitotic activity by 5'-bromo-2'-deoxyuridine (BrdU)
      incorporation and proliferating cell nuclear antigen (PCNA) immunodetection.
      Additionally, immunodetection of c-Kit receptor, a marker of differentiating
      spermatogonia in rodents, and of alpha- and beta-spectrins, as constituents of
      the spectrosome and the fusome, has been performed. Ultrastructurally, nuclei of
      stage I spermatogonia present the same mottled aspect in dogfish as
      undifferentiated spermatogonia nuclei in rodents. Moreover, intercellular bridges
      are not observed in dogfish spermatogonia, although they are present in stage II
      spermatogonia. BrdU and PCNA immunodetection underlines their low mitotic
      activity. The presence of a spectrosome-like structure, a cytological marker of
      the germline stem cells in Drosophila, has been observed. Our results constitute
      the first step in the study of spermatogonial stem cells and their niche in the
      dogfish.

PMID- 18340469
TI  - Further examination of the candidate genes in chromosome 12p13 locus for late
      onset Alzheimer disease.
AB  - A broad region on chromosome 12p13 has been intensely investigated for novel
      genetic variants associated with Alzheimer disease (AD). We examined this region
      with 23 microsatellite markers using 124 North European (NE) families and 209
      Caribbean Hispanic families with late-onset AD (FAD). Significant evidence for
      linkage was present in a 5-cM interval near 20 cM in both the NE FAD (LOD = 3.5)
      and the Caribbean Hispanic FAD (LOD = 2.2) datasets. We further investigated
      these families and an independent NE case-control dataset using 14 single
      nucleotide polymorphisms (SNPs). The initial screening of the region at
      approximately 20 cM in the NE case-control dataset revealed significant
      association between AD and seven SNPs in several genes, with the strongest result
      for rs2532500 in TAPBPL (p = 0.006). For rs3741916 in GAPDH, the C allele, rather
      than the G allele as was observed by Li et al. (Proc Natl Acad Sci U S A
      101(44):15688-15693, 2004), was the risk allele. When the two family datasets
      were examined, none of the SNPs were significant in NE families, but two SNPs
      were associated with AD in Caribbean Hispanics: rs740850 in NCAPD2 (p = 0.0097)
      and rs1060620 in GAPDH (p = 0.042). In a separate analysis combining the
      Caribbean Hispanic families and NE cases and controls, rs740850 was significant
      after correcting for multiple testing (empirical p = 0.0048). Subsequent
      haplotype analyses revealed that two haplotype sets-haplotype C-A at SNPs 6-7
      within NCAPD2 in Caribbean Hispanics, and haplotypes containing C-A-T at SNPs 8
      10 within GAPDH in Caribbean Hispanic family and NE case-control datasets-were
      associated with AD. Taken together, these SNPs may be in linkage disequilibrium
      with a pathogenic variant(s) on or near NCAPD2 and GAPDH.

PMID- 18340470
TI  - Localised Fusobacterium necrophorum infections: a prospective laboratory-based
      Danish study.
AB  - During a 3-year prospective laboratory-based study in Denmark from 1998 to 2001,
      all patients who were diagnosed with localised Fusobacterium necrophorum
      infections were registered with the purpose of describing the variety of
      localised infections caused by F. necrophorum, especially in the head. We found
      267 patients, most of them previously healthy, with localised F. necrophorum
      infections in the head and neck. In children, F. necrophorum caused otitis media
      and solitary abscess formation in cervical lymphadenitis. In adolescents, F.
      necrophorum was found in 21% of peritonsillar abscesses. We also found F.
      necrophorum in young adults with tonsillitis and in middle-aged adults with
      sinusitis. F. necrophorum was found in substantial amounts and as the only
      bacterial pathogen in the majority of patients. All 267 patients recovered
      without sequelae. We found another 21 localised non-head-and-neck-associated F.
      necrophorum infections, mainly subcutaneous wound infections in adults. This
      study shows that F. necrophorum causes a variety of localised infections,
      especially in the head and neck region, with a characteristic age distribution.
      We recommend that anaerobic culture is performed on swabs from children with
      recurrent otitis media and adolescents with non-streptococcal group A
      tonsillitis.

PMID- 18340471
TI  - Wii knee.
AB  - We present the case of a 16-year-old boy who injured his knee whilst playing on
      the video games console Nintendo Wii. The patient presented with an acutely
      swollen and painful knee to the emergency department of our institution. Initial
      radiographs revealed an effusion and an osteochondral fracture. Further imaging
      with magnetic resonance imaging demonstrated evidence of lateral patella
      dislocation with medial patello-femoral ligamentous damage and a large femoral
      osteochondral fracture. The patient was successfully treated with surgical
      fixation of the osteochondral fragment and medial patello-femoral ligament
      repair. This case highlights the force that can be generated whilst using these
      new games consoles.

PMID- 18340472
TI  - Comparing methodologies for the cost estimation of hospital services.
AB  - The aim of the study was to determine whether the total cost estimate of a
      hospital service remains reliable when the cost components of bottom-up
      microcosting were replaced by the cost components of top-down microcosting or
      gross costing. Total cost estimates were determined in representative general
      hospitals in the Netherlands for appendectomy, normal delivery, stroke and acute
      myocardial infarction for 2005. It was concluded that restricting the use of
      bottom-up microcosting to those cost components that have a great impact on the
      total costs (i.e., labour and inpatient stay) would likely result in reliable
      cost estimates.

PMID- 18340473
TI  - PVA-alginate immobilized cells for anaerobic ammonium oxidation (anammox)
      process.
AB  - The feasibility of an anaerobic ammonium oxidation (anammox) process combined
      with a cell-immobilization technique for autotrophic nitrogen removal was
      investigated. Anammox biomass was cultivated from local activated sludge and
      achieved significant anammox activity in 6 months. The development of a mature
      anammox biomass was confirmed by fluorescence in situ hybridization (FISH)
      analysis and off-line activity measurements. The abundance fraction of the
      anammox bacteria determined by FISH analysis was estimated by software. The
      anaerobic ammonia oxidizers occupied almost half of the total cells.
      Additionally, the anammox biomass was granulated as spherical gel beads of 3-4 mm
      in diameter by using a cell-immobilization technique. The nitrogen removal
      activity was proved to be successfully retained in the beads, with about 80% of
      nitrogenous compounds (NH(4) (+), NO(2) (- )and total nitrogen) removed after 48
      h. These results offer a promising technique for the preservation of anammox
      microorganisms, the protection of them against the unfavorable surroundings, and
      the prevention of biomass washout towards the implementation of sustainable
      nitrogen elimination biotechnology. This is the first report on the
      immobilization of anammox biomass as gel beads.

PMID- 18340474
TI  - Endothelial cytoskeletal elements are critical for flow-mediated dilation in
      human coronary arterioles.
AB  - Mitochondrial H2O2 contributes to flow-mediated dilation (FMD) in human coronary
      arterioles (HCA). We examined the hypothesis that the endothelial cytoskeleton
      plays a critical role in transducing endothelial wall shear stress into a
      stimulus for releasing mitochondrial ROS. Phallacidin together with alpha-, beta
      tubulin antibodies and Mito-Tracker Red showed the proximity of F-actin,
      microtubules and mitochondria in endothelial cells. Cytochalasin D (CytoD) and
      nocodazole (Noc) disrupted endothelial F-actin and microtubules in HCA,
      respectively, concurrent with a reduction in the generation of cytosolic and H2O2
      (hydroethidine and dichlorodihydrofluorescein fluorescence) and mitochondrial
      superoxide (mitoSox) during flow (control: 3.5 +/- 1.6, Cyto D: 0.51 +/- 0.2,
      Noc: 0.81 +/- 0.6). FMD, but not the dilation to bradykinin or papaverine, was
      reduced by Cyto D (26 +/- 10% vs. 56 +/- 3%) or Noc (26 +/- 11% vs. 58 +/- 7%).
      These results suggest that cytoskeletal elements are a critical component of the
      signaling mechanism linking endothelial shear stress and mitochondrial release of
      ROS in the human coronary microcirculation.

PMID- 18340475
TI  - [Medical guideline for the treatment of adults with congenital heart
      abnormalities of the German-Austrian-Swiss Cardiology Specialty Society].

PMID- 18340476
TI  - Effect of nutrition on toxicity of contaminants to the epibenthic amphipod Melita
      plumulosa.
AB  - The amphipod Melita plumulosa is commonly used to assess the toxicity of
      contaminated sediments. Seven-day-old M. plumulosa are <1 mm in size, and during
      10-day tests in sandy sediments with low nutritional value, starvation can cause
      >50% mortality. In sediment toxicity tests, therefore, it can be difficult to
      determine if toxicity is due to contaminants or starvation, particularly in
      contaminated sandy sediments. This study investigated the influence of amphipod
      age and food addition on amphipod survival in toxicity tests. The 4-day LC(50)
      increased linearly from 120 to 470 microg/L when M. plumulosa age at the
      beginning of the test increased from 5 to 30 days. The addition of food as algae
      or fish food did not significantly affect the sensitivity of 11-day-old M.
      plumulosa (11-d Mp) to dissolved copper over 4 days in water-only tests. The
      survival of 11-d Mp in water-only tests over 10 days was poor without feeding,
      but when fed fish food, the 10-day LC(50) was 76 +/- 15 microg/L. In sediment
      tests, feeding 0.063 mg fish food/amphipod on days 3 and 7 of 10-day tests
      consistently resulted in greater than 80% survival of 11-d Mp for a range of
      clean, sandy sediments, which had low amphipod survival without added food. Algae
      were not always suitable as a food source, as their growth can be stimulated by
      nutrients released from sediment and was inhibited by contaminants. The toxicity
      of most contaminated sediments was not ameliorated by the addition of food,
      suggesting that food addition was suitable for inclusion in routine testing
      protocols for this amphipod.

PMID- 18340477
TI  - Computerized tomography virtual endoscopy in evaluation of upper urinary tract
      tumors: initial experience.
AB  - PURPOSE: To assess the usefulness of CT virtual endoscopy (VE) as an integration
      of CT-urography, for the detection of upper urinary tract tumor in patients with
      hematuria. MATERIALS AND METHODS: Fourteen patients with hematuria and high risk
      of transitional cell carcinoma of the upper urinary tract underwent urinary
      cytology, ultrasonography, excretory urography, cystoscopy, CT-urography with VE,
      and optical ureteroscopy. The CT urograms and VE were correlated with the
      pathological findings of surgical specimen (6/14) and cytological examination of
      ureteroscopy biopsy (8/14). RESULTS: VE revealed three renal pelvic and one
      ureteral tumors, not producing further information did not detected at CT
      urography. In two patients VE showed findings strongly indicative of
      malignancies, not noticed at CT-urography: ureteroscopic biopsy revealed an
      advanced dysplastic lesion and a malignancy, confirmed at surgery. In one patient
      VE was questionable (narrowing of the distal ureter) and ureteroscopic biopsy
      revealed an inflammation. Finally, VE diagnosed a fibrosis of the lumbar ureteral
      tract, confirmed at ureteroscopic biopsy. In other six patients, VE and
      ureteroscopy did not find abnormalities. CONCLUSION: VE should be useful as an
      integration of CT-urography for a complete evaluation of the upper urinary tract
      in patients with suspected tumor, limiting the need for fiberoptic ureteroscopic
      examination.

PMID- 18340478
TI  - The frequency of the plicae palmatae in the uterine cervix on MR imaging.
AB  - BACKGROUND: The plicae palmatae is a developmental remnant of the Mullerian
      ductal fusion, which is demonstrated as a ridge of low intensity in the cervical
      canal on axial T2-weighted MR images. The identification of the plicae palmatae
      on MR imaging is beneficial for avoiding misinterpretation of this finding as
      anomalous uterine septum. The current study is performed to investigate the
      frequency of this finding and its variation among different age groups. METHODS:
      Axial T2-weighted images in 433 subjects were evaluated regarding the presence of
      the plicae palmatae and uterine anomaly. RESULTS: The frequency of the plicae
      palmatae was 47.5-53.2% in the third to fifth decade groups, but it was
      significantly lower in the sixth decade group (24.8%) than in the fifth decade
      group (53.2%). In three subjects with uterine anomalies, the plicae palmatae was
      recognized in a bicornuate uterus with single cervix, whereas it was not
      identified in unicornuate uterus and bicornuate uterus with duplicated cervices.
      CONCLUSION: The plicae palmatae is commonly encountered in routine MR images of
      normal uterus, especially in reproductive-aged women.

PMID- 18340479
TI  - Preoperative neutrophil-to-lymphocyte ratio as a prognostic predictor after
      curative resection for hepatocellular carcinoma.
AB  - BACKGROUND: This study was designed to evaluate the impact of an elevated
      preoperative neutrophil-to-lymphocyte ratio (NLR) on outcome after curative
      resection for hepatocellular carcinoma (HCC). METHODS: Patients undergoing
      resection for HCC from January 1994 to May 2007 were identified from the
      hepatobiliary database. Demographics, laboratory analyses, and histopathology
      data were analyzed. RESULTS: A total of 96 patients were identified with a median
      age at diagnosis of 65 (range, 15-85) years. The 1-, 3-, and 5-year overall
      survival rates were 80%, 58%, and 52%, respectively. Although the presence of
      microvascular invasion, NLR >or=5, and R1 resection margin were adverse
      predictors of overall survival, there were no independent predictors identified
      on multivariate analysis. The 1-, 3-, and 5-year disease-free survival rates were
      74%, 63%, and 57%, respectively. Preoperative tumor biopsy, NLR >or= 5, multiple
      liver tumors, microvascular invasion, and R1 resection margin were all predictors
      of poorer disease-free survival. Multivariate analysis showed that a NLR >or= 5
      and R1 resection margin were independent predictors of poorer disease-free
      survival. The median disease-free survival of those with a NLR >or= 5 was 8
      months compared with 18 months for those with a NLR < 5. CONCLUSION: Preoperative
      NLR >or= 5 was an adverse predictor of disease-free and overall survival.

PMID- 18340480
TI  - Evidence for the role of perioperative PTH measurement after total thyroidectomy
      as a predictor of hypocalcemia.
AB  - BACKGROUND: Total thyroidectomy is now accepted worldwide as the standard
      surgical procedure for the management of benign bilateral nodular thyroid
      disease. Hypocalcemia is the most common complication of that procedure and a
      variety of strategies for diagnosing and managing post-thyroidectomy hypocalcemia
      have been advocated. Increasingly, the use of intact parathyroid hormone (PTH)
      has been utilized to try to predict those patients at risk of developing post
      thyroidectomy hypocalcemia. METHODS: A Medline search of English language
      literature was performed and we reviewed the evidence in relation to the
      following three issues: the accuracy of PTH in predicting hypocalcemia, the
      optimal timing for measuring PTH, and the routine use of oral calcium
      supplements. RESULTS: Post-thyroidectomy PTH levels accurately predict
      hypocalcemia but lack 100% accuracy. Progressive and severe hypocalcemia is
      unlikely in the setting of a normal PTH level and hence PTH can be cautiously
      used to facilitate discharge within 24 h for many patients. In addition, PTH
      levels can be used to implement early treatment with calcium and/or vitamin D
      supplements to reduce the incidence and severity of hypocalcemia. A single PTH
      measurement taken any time from 10 min to several hours postoperative will
      provide equally accurate results for predicting post-thyroidectomy hypocalcemia.
      Routine use of oral calcium supplements may reduce the incidence and severity of
      post-thyroidectomy hypocalcemia. CONCLUSION: Postoperative PTH can be used to
      stratify the risk of patients developing hypocalcemia after thyroidectomy. In
      addition, the routine use of oral calcium supplements can lead to decreased
      incidence and severity of post-thyroidectomy hypocalcemia. Protocols based on PTH
      and the routine use of oral calcium supplements can lead to improved patient
      outcomes after thyroidectomy.

PMID- 18340481
TI  - Previous laparotomy is not a contraindication to laparoscopy-assisted gastrectomy
      for early gastric cancer.
AB  - BACKGROUND: Laparoscopic procedures have generally been considered to be
      contraindicated in patients with a history of laparotomy because of a high risk
      of enteric injury during the procedure. Laparoscopy-assisted gastrectomy (LAG)
      has been used increasingly in the treatment of early gastric cancer, but its
      indication for patients with a history of laparotomy remains unclear. The aim of
      the present study was to estimate whether LAG is contraindicated for the patient
      with a history of laparotomy (PSURG). METHODS: From January 2003 to March 2006,
      139 patients with early gastric cancer underwent LAG with curative intent in our
      institute. Fifty were PSURG patients, and the remaining 89 patients underwent LAG
      without any history of laparotomy (NSURG). Operative and early postoperative
      outcomes were compared between the groups. RESULTS: Appendectomy and
      gynecological surgery were the predominant procedures performed in the PSURG
      group prior to undergoing LAG, involving 28 patients (56.0%) and 16 patients
      (32.0%), respectively. Detachment of adhesion above the umbilicus was required in
      25 PSURG patients (50.0%). There was no significant difference in operative and
      postoperative results between the two groups, although 1 PSURG patient developed
      symptoms of bowel injury on the first postoperative day, probably caused during
      the laparoscopic procedure for dissection of a jejuno-jejunal adhesion.
      CONCLUSIONS: There was no difference in outcome following LAG between the PSURG
      and NSURG groups in the present study. The PSURG patient is not contraindicated
      for LAG assuming careful attention is given for all operative procedures,
      including port insertion and dissection of intra-abdominal adhesions.

PMID- 18340482
TI  - Subtotal and near total versus total thyroidectomy for the management of
      multinodular goiter.
AB  - BACKGROUND: The purpose of the present work was to compare rates of postsurgical
      complications following thyroidectomy for multinodular goiter through a
      retrospective multicenter cohort study. METHODS: All cases of thyroidectomy
      (total-TT; near total-NT; and bilateral subtotal-ST) performed in two hospitals
      from 1990 to 2005 were studied to determine the incidence of complications after
      each procedure. Follow-up checked injury of laryngeal nerves, hypoparathyroidism,
      hypothyroidism, pathology recurrence, and appearance of neoplasm. RESULTS: There
      were 6,223 cases: TT, n = 3,834 (61.6%); ST, n = 2,238 (36%); and NT, n = 151
      (2.4%) NT). Of this total, 2,758 (44.3%) patients were men and 3,465 (55.7%) were
      women with a mean age of 48.7. Postoperative mean follow-up was 7 years, 2
      months. Permanent recurrent laryngeal nerve (RLN) injury was observed in 1.4% in
      the TT group, 1.2% in the ST group, and 1.1% in the NT group (p > 0.1). Permanent
      hypocalcemia was observed in 2% in TT group, 1.9% in the ST group, and 2% in the
      NT group (p > 0.1). Permanent hypothyroidism occurred in all patients in the TT
      and NT groups, compared to 91% of the patients in the ST group (p > 0.1).
      Recurrence of benign disease was noted in 491 patients (20.5% of ST and NT cases
      combined; p < 0.05), n = 482 (21.5%) after ST and n = 9 (5.9%) after NT. Of the
      patients with recurrence, 173 needed a completion thyroidectomy. Malignant
      transformation was observed in 28 cases. CONCLUSIONS: There is no statistically
      significant difference in complications among TT, NT, and ST groups. Partial
      thyroidectomies provide no decisive advantage over total thyroidectomies in terms
      of subsequent requirements of supplemental hormone therapy. The rate of
      reoperation in cases of recurrent pathology and incidental carcinoma was high.

PMID- 18340483
TI  - Surgical resection of stage IV colorectal cancer and prognosis.
AB  - BACKGROUND: Colorectal cancer (CRC) harbors accumulated genetic alterations with
      cancer progression, which results in uncontrollable disease. To regulate the most
      malignant CRC, we have to know the most dismal phenotype of stage IV disease.
      METHODS: A retrospective review of the Kitasato University Hospital was performed
      (from 1990 to 2001) to extract the 162 resected stage IV CRC. Clinical variables
      were tested for their relationship to survival in a multivariate prognostic
      analysis and revealed the interaction of the prognostic factors. RESULTS: In
      stage IV CRC with noncurable resection, the most robust univariate predictors for
      poor prognosis were preoperative high value of CA19-9, peritoneal dissemination,
      depth of invasion, age, extent of liver metastases, pathologic lymph node
      metastasis status, and gender as tumor factors, and postoperative therapy,
      perioperative transfusion, and lymph node dissection extent as treatment factors.
      Among these factors, postoperative therapy (p < 0.0001), perioperative
      transfusion (0.0002), CA19-9 (0.001), extent of liver metastases (0.004), and
      peritoneal dissemination (0.02) were identified as independent prognostic factors
      by multivariate analysis. Interestingly, among the independent prognostic
      factors, treatment factors did not depend upon tumor factors and the combination
      of the three tumor factors (CA19-9, extent of liver metastases, and peritoneal
      dissemination) can clearly classify the patients into the definite prognostic
      groups. CONCLUSION: Our results suggested that the most dismal CRC harbors three
      definite vectors that may represent the strongest phenotype of putative systemic
      immune (CA19-9), distant metastasis (extent of liver metastases), and local
      progression (peritoneal dissemination).

PMID- 18340484
TI  - Endovascular aortic aneurysm repair with the talent stent-graft: outcomes in
      patients with large iliac arteries.
AB  - The purpose of this study is to report outcomes following endovascular aneurysm
      repair (EVAR) of abdominal aortic aneurysm (AAA) in patients with ectatic common
      iliac arteries (CIAs). Of 117 AAA patients treated by EVAR between 1998 and 2005,
      87 (74%) had CIAs diameters <18 mm and 30 (26%) patients had one or more CIA
      diameters >18 but <25 mm. All patients were treated with Talent stent-grafts, 114
      bifurcated and 3 AUI devices. Departmental databases and patient records were
      reviewed to assess outcomes. Technical success, iliac-related outcome, and iliac
      related reintervention (IRSI) were analyzed. Patients with EVAR extending into
      the external iliac artery were excluded. Median (range) follow-up for the study
      group was 24 (1-84) months. Initial technical success was 98% for CIAs <18 mm and
      100% for CIAs >/=18 mm (p = 0.551). There were three distal type I endoleaks (two
      in the ectatic group) and six iliac limb occlusions (one in an ectatic patient);
      there were no statistically significant differences between groups (p = 0.4).
      There were nine IRSIs (three stent-graft extensions, six femorofemoral crossover
      grafts); three of these patients had one or both CIAs >/=18 mm (p = 0.232). One
      year freedom from IRSI was 92% +/- 3% and 84% +/- 9% for the <18-mm and >/=18-mm
      CIA groups, respectively (p = 0.232). We conclude that the treatment of AAA by
      EVAR in patients with CIAs 18-24 mm appears to be safe and effective, however, it
      may be associated with more frequent reinterventions.

PMID- 18340485
TI  - Effect on quality of life of continuous positive airway pressure in patients with
      obstructive sleep apnea syndrome: a meta-analysis.
AB  - Continuous positive airway pressure (CPAP) is the standard treatment for
      obstructive sleep apnea syndrome (OSAS). However, the impact of CPAP on quality
      of life (QOL) is controversial. The aim of this study was to systematically
      review and determine whether CPAP improves QOL in patients with OSAS. We
      performed a comprehensive literature search to identify studies published between
      1966 and 2007 comparing values of CPAP with control. Weighted mean difference
      (WMD) was used to analyze the data. The pooled WMD was calculated by using a
      fixed or random-effect model. The outcomes for 1,256 patients from 16 studies, of
      whom 656 patients underwent CPAP and 600 were controls, were included. CPAP led
      to significant improvements in the Nottingham health profile part 2 (WMD=1.657;
      95% CI=3.005, -0.308; p=0.016), but there was no difference in other general QOL
      scores. Patients undergoing CPAP scored better in physical function (WMD=3.457;
      95% CI=0.144, 6.771; p=0.041), body pain (WMD=4.017; 95% CI= -0.008, 8.042;
      p=0.05), energy vitality (WMD=6.984; 95% CI = 0.557, 13.411; p=0.033) and
      physical component summary (PCS) (WMD=2.040; 95% CI=0.045, 4.035; p=0.045) using
      the SF-36 tool. This meta-analysis shows that CPAP does not improve general QOL
      scores but does improve physical domains and vitality. Study design and QOL
      questionnaire tools are important to capture and evaluate information
      efficiently. However, generic QOL instruments may not be adequate in detecting
      important changes in quality of life in patients with OSAS.

PMID- 18340486
TI  - Behavioral responses of adult Sitophilus granarius to individual cereal
      volatiles.
AB  - The antennae of Sitophilus granarius (L.) (Coleoptera: Curculionidae) adults
      detect a wide variety of compounds in the odor blend of various cereal grains
      (Germinara et al., Tec. Molit., 53:27-34, 2002). In the present study, we looked
      at the behavioral responses of the granary weevil to 20 of these individual
      volatiles (aliphatic alcohols, aldehydes, ketones, and aromatics) in a two-choice
      pitfall olfactometer, using the aggregation pheromone and propionic acid as the
      attractant and repellent controls, respectively. Five doses, ranging from 1
      microg to 1 mg, of each compound were tested. At least one concentration of eight
      compounds attracted beetles but required doses 1,000- to 5,000-fold higher than
      the concentration of aggregation pheromone to elicit a response. Three compounds,
      while attractive at lower concentrations, acted as repellents at higher doses.
      Twelve compounds were repellent at concentrations similar to the quantity of
      propionic acid that significantly repelled beetles. The data show that granary
      weevil adults have the ability to respond behaviorally to a wide range of cereal
      volatiles and that responses may change as a function of concentration. The
      results suggest that host finding behavior of weevils will depend on the balance
      of positive and negative volatile stimuli from grain as the relative
      concentrations of volatiles may change during storage. An understanding of how
      the weevils respond to such changes could be useful for the development of
      effective integrated pest management strategies.

PMID- 18340487
TI  - Enantiospecific effect of pulegone and pulegone-derived lactones on Myzus
      persicae (Sulz.) settling and feeding.
AB  - The effect of pulegone chiral center configuration on its antifeedant activity to
      Myzus persicae was examined. Biological consequences of structural modifications
      of (R)-(+)- and (S)-(-)-pulegone, the lactonization, iodolactonization, and
      incorporation of hydroxyl and carbonyl groups were studied, as well. The most
      active compounds were (R)-(+)-pulegone (1a) and delta-hydroxy-gamma-spirolactones
      (5S,6R,8S)-(-)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2-one (5b) and
      (5R,6S,8S)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2-one (6b) derived from
      (S)-(-)-pulegone (1b). The compounds deterred aphid probing and feeding at
      preingestional, ingestional, and postingestional phases of feeding. The
      preingestional effect of (R)-(+)-pulegone (1a) was manifested as difficulty in
      finding and reaching the phloem (i.e., prolonged time preceding the first contact
      with phloem vessels), a high proportion of probes not reaching beyond the
      mesophyll layer before first phloem phase, and/or failure to find sieve elements
      by 20% of aphids during the 8-hr experiment. The ingestional activity of (R)-(+)
      pulegone (1a) and hydroxylactones 5b and 6b resulted in a decrease in duration of
      phloem sap ingestion, a decrease in the proportion of aphids with sustained sap
      ingestion, and an increase in the proportion of aphid salivation in phloem. delta
      Keto-gamma-spirolactone (5R,8S)-(-)-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2,6
      dione (8b) produced a weak ingestional effect (shortened phloem phase). The
      postingestional deterrence of (R)-(+)-pulegone (1a) and delta-hydroxy-gamma
      spirolactones (5R,6S,8R)-(+)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]-decan-2
      one (5a), 5b, (5S,6R,8R)-6-hydroxy-4,4,8-trimethyl-1-oxaspiro[4.5]decan-2-one
      (6a), 6b, and delta-keto-gamma-spirolactone 8b prevented aphids from settling on
      treated leaves. The trans position of methyl group CH3-8 and the bond C5-O1 in
      lactone 6b appeared to weaken the deterrent activity in relation to the cis
      diastereoisomer (5b).

PMID- 18340488
TI  - Targeting VEGF, EGFR, and other interacting pathways for gastric cancer-promises
      and reality.

PMID- 18340490
TI  - Fingerprinting lymph node metastases.

PMID- 18340491
TI  - Can intraoperative intraperitoneal free cancer cell detection techniques identify
      patients at higher recurrence risk following curative colorectal cancer
      resection? A meta-analysis.

PMID- 18340492
TI  - Extensive pathological analysis of selected melanoma sentinel lymph nodes: high
      metastasis detection rates at reduced workload.
AB  - BACKGROUND: Extensive pathological workup of sentinel lymph nodes (SLNs) in
      melanoma detects more patients with metastasis-positive SLNs than do routine
      protocols, but at the cost of high laboratory workloads. We aimed to design a
      protocol that reduced this workload without compromising metastasis detection.
      METHODS: We analyzed 920 SLNs from 321 consecutive patients with melanoma by
      complete step sectioning and immunohistochemistry. We designed different models
      to theoretically reduce the number of histological sections examined and compared
      the results from these simulations with results obtained with our extended
      protocol, with the restricted national Danish protocol, and with the protocol
      recommended by the European Organization for Research and Treatment of Cancer
      (EORTC). RESULTS: The extended protocol increased the metastasis detection rate
      by 22% (95% confidence interval, 11-34; 30.8% vs. 25.2%, P < .0001) compared with
      the national Danish protocol, and it had a similar rate to that reported by the
      EORTC (30.8% vs. 29.4%, P = .6229). The workload associated with complete step
      sectioning could be reduced by 40% by focusing step sectioning on the SLNs with
      the highest gamma counts, while examining SLNs with lower gamma counts with one
      to three central sections. The false-negative rate for detecting metastases with
      this reduced protocol was 6% compared with complete step sectioning. CONCLUSIONS:
      Combining complete step sectioning of SLNs with immunohistochemistry ensures high
      metastasis detection rates. Workloads can be markedly reduced with only a slight
      increase in the false-negative rate by focusing analysis on the SLNs most likely
      to contain metastases, i.e., those with the highest gamma counts.

PMID- 18340493
TI  - Surgical complications and the risk factors of laparoscopy-assisted distal
      gastrectomy in early gastric cancer.
AB  - BACKGROUND: Information on surgical complications of laparoscopy-assisted distal
      gastrectomy (LADG) and their risk factors is limited in the literature despite
      increasing popularity of this procedure. This study was performed to identify the
      surgical complications and their associated risk factors of LADG in early gastric
      cancer. METHODS: LADG was performed in 347 gastric cancer patients from January
      2002 to December 2006 at the Korean National Cancer Center by four surgeons with
      ample experience of open gastric surgery before LADG. LADG indications for cases
      of gastric cancer at our institution are preoperatively diagnosed cT1N0 or cT1N1,
      except in cases with an absolute indication for endoscopic resection. Lymph node
      dissection of more than D1 + beta was performed in all patients. Intraoperative
      and postoperative complications were reviewed and their risk factors were
      retrospectively analyzed by prospective database information. RESULTS: Forty
      complications occurred in 34 patients (9.8%), but there was no mortality.
      Intraoperative complications occurred in nine patients (2.6%), and open
      conversion was performed in eight (2.3%) of these patients. Early and late
      postoperative complications occurred in 21 (6.1%) and 10 (2.9%) patients,
      respectively. The most serious complication was vascular injury resulting in
      bleeding or organ ischemia, which occurred in seven patients. Degree of lymph
      node dissection and surgical inexperience were found to be risk factors of
      surgical complication (P = .023, odds ratio 2.832, 95% confidence interval 1.155
      6.946 vs. P = .028, odds ratio 2.975, 95% confidence interval 1.127-7.854).
      CONCLUSIONS: Lymph node dissection during LADG should be performed cautiously to
      prevent surgical complications like vascular injuries, especially during the
      surgeon's early learning period.

PMID- 18340495
TI  - Clinicopathologic characteristics and prognosis for young gastric adenocarcinoma
      patients after curative resection.
AB  - BACKGROUND: Conflicting results from previous studies on gastric adenocarcinoma
      (GC) in young patients have led to controversy surrounding the prognosis for
      young GC patients. METHODS: The authors studied 6954 patients with GC who
      received curative resections. They were classified into three groups: those aged
      40 years or less ("young," 12.7%); those aged 41-65 years ("middle-aged," 66.7%);
      and those aged more than 65 years ("elderly," 20.6%). Clinicopathologic
      characteristics and overall survival rates were analyzed. RESULTS: Young patients
      were predominately female and had tumors that were histologically
      undifferentiated. However, in regard to T4 invasion, N3 lymph node metastasis,
      and TNM stage IV, the characteristics of the tumors of young patients were
      similar to those of middle-aged and elderly patients. Overall survival rate was
      significantly better in young patients than middle-aged patients (P = .018) and
      elderly patients (P < .001). Stratified by TNM stage, young patients showed
      better overall survival at stage I than middle-aged patients, and at stages I,
      II, and IIIa than elderly patients. Multivariate analysis indicated that age was
      an independent prognostic factor (as well as gender, operation type, depth of
      invasion, and lymph node status). CONCLUSIONS: The predominance of female cases
      and tumors that were histologically undifferentiated were distinctive
      characteristics in young patients. Young patients could gain a survival benefit
      after curative resection with stage I disease.

PMID- 18340496
TI  - Spectral and fractal analysis of cerebellar activity after single and repeated
      brain injury.
AB  - The cerebellum, even when not directly damaged, is potentially interesting for
      understanding the adaptive responses to brain injury. Cerebellar electrocortical
      activity (ECoG) in rats was studied using spectral and fractal analysis after
      single and repeated unilateral injury of the parietal cortex. Local field
      potentials of cerebellar paravermal cortex were recorded before brain injury, in
      the acute phase (up to 2.5 hours) after a first injury of anesthetized rats, and
      then before and after second, third, and, in some cases, fourth injury. Relative
      gamma power (32.1-128.0 Hz) and fractal dimension of ECoGs were temporarily
      increased after the first injury. However, there was a permanent mild increase in
      gamma activity and a mild increase in the fractal dimension of cerebellar
      activity as a chronic change after repeated remote brain injury. There was a
      negative linear correlation between the normalized difference in fractal
      dimensions and normalized difference in gamma powers of cerebellar activity only
      in the case of repeated brain injury. This is the first study showing that
      correlation between the parameters of spectral and fractal analyses of cerebellar
      activity can discriminate between single and repeated brain injuries, and is,
      therefore, a promising approach for identifying specific pathophysiological
      states.

PMID- 18340497
TI  - Asymptotic enumeration of RNA structures with pseudoknots.
AB  - In this paper, we present the asymptotic enumeration of RNA structures with
      pseudoknots. We develop a general framework for the computation of exponential
      growth rate and the asymptotic expansion for the numbers of k-noncrossing RNA
      structures. Our results are based on the generating function for the number of k
      noncrossing RNA pseudoknot structures, Sk(n), derived in Bull. Math. Biol.
      (2008), where k-1 denotes the maximal size of sets of mutually intersecting
      bonds. We prove a functional equation for the generating function Sigman>or=0
      Sk(n)zn and obtain for k=2 and k=3, the analytic continuation and singular
      expansions, respectively. It is implicit in our results that for arbitrary k
      singular expansions exist and via transfer theorems of analytic combinatorics, we
      obtain asymptotic expression for the coefficients. We explicitly derive the
      asymptotic expressions for 2- and 3-noncrossing RNA structures. Our main result
      is the derivation of the formula S3(n) approximately 10.4724.4!/n(n-1)...(n
      4)(5+[sqrt]21/2)n.

PMID- 18340498
TI  - Selective surgical treatment of patients with rectal carcinoma and unresectable
      synchronous metastases based on response to preoperative chemotherapy.
AB  - BACKGROUND: The time schedule for chemotherapy and primary tumor resection in
      patients with rectal carcinoma (RC) and unresectable synchronous metastases (USM)
      is not well defined. We evaluated whether response to chemotherapy is an
      appropriate criterion for deciding to perform surgery. METHODS: We treated 22
      patients with RC and USM who received chemotherapy and were regularly evaluated.
      After documentation of a partial remission (PR) or stable disease (SD), patients
      were offered resection of the primary tumor. Results were compared with those of
      a historical control group of 42 patients who underwent immediate surgery.
      RESULTS: Seven patients had a PR, four showed SD, and 11 progressed under
      chemotherapy. Seven patients underwent resection of the primary tumor (no
      perioperative mortality). The median survival for all 22 patients was 20.2
      months. Patients with primary tumor resection survived 27.2 months, whereas
      patients without resection survived only 12.4 months (p = 0.017). The median
      survival in the control group was 13.5 months (perioperative mortality, 9.5%).
      CONCLUSION: Chemotherapy and response-dependent resection of the primary tumor
      results in the same survival time as that attained with immediate surgery.
      Patients who face a poor prognosis due to progressive disease are thereby spared
      the risks of major rectal surgery.

PMID- 18340499
TI  - Preliminary results of the laparoscopic adjustable gastric banding procedure by a
      new generation of silicone band: MIDBAND.
AB  - BACKGROUND: The surgical treatment of morbid obesity by laparoscopic adjustable
      gastric banding has become a "gold standard" in Europe. Currently, five types of
      silicone bands are used in the majority of countries performing bariatric
      surgery. METHODS: The MIDBAND was introduced to the European market in 2000. It
      is placed around the stomach using the Pars Flaccida technique described by
      Forsell. A prospective multicentric study on 113 cases was carried out to
      evaluate technical feasibility, complications, and the midterm weight loss
      outcomes (2 years). RESULTS: The percentage of excess body weight loss was 52.58%
      at 2 years. Perioperative mortality was nil and the complication rate was low
      (slippage <2%). CONCLUSION: These encouraging results require longer-term studies
      to validate this procedure.

PMID- 18340500
TI  - IFSO guidelines for safety, quality, and excellence in bariatric surgery.

PMID- 18340501
TI  - Pain and deformity of the index finger in a 41-year-old woman.

PMID- 18340502
TI  - Sclerosing epithelioid fibrosarcoma: case presentation and a systematic review.
AB  - In sclerosing epithelioid fibrosarcoma (SEF), a rare variant of low-grade
      fibrosarcoma, treatment results and therapeutic options are poorly characterized.
      We systematically analyzed the data of all 89 patients (43 female, 46 male; mean
      age, 47 years [range, 14-87 years]) reported in the literature concerning
      clinical presentation, histopathology, differential diagnosis, treatment,
      survival rates, and prognosis, and we present an additional case. Information
      detailing treatment, disease control, and followup was available in 60 (67%), 75
      (84%), and 68 patients (76%), respectively. Case history was variable with one
      third of patients reporting a painful, enlarging mass. Ten patients (13%)
      presented with metastases, 23 (31%) had metastases develop after diagnosis, and
      28 (37%) had local recurrence. Low cellularity, mild pleomorphy, and sclerotic
      hyaline matrix of SEF suggest a benign clinical behavior, and cell morphology
      allows for the wide differential diagnosis of benign, pseudosarcomatous, and
      malignant proliferations. In addition to surgery, 11 patients (15%) had
      chemotherapy, 22 (29%) had postoperative radiation therapy, and three (4%) had a
      combination of both. Twenty-three patients (34%) died from their disease after a
      mean of 46 months, 24 (35%) were alive with disease, and 20 (31%) were alive
      without evidence of disease. Patients with SEF of the head and neck had the worst
      prognosis. LEVEL OF EVIDENCE: Level III, prognostic study. See the Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 18340503
TI  - Generic tobramycin elutes from bone cement faster than proprietary tobramycin.
AB  - Elution of antibiotics from antibiotic-loaded polymethylmethacrylate (AL-PMMA)
      increases when soluble particulate filler is added to increase the permeability
      of the PMMA. Antibiotic powder is in itself soluble particulate filler. For
      greater volume fractions of filler, greater elution occurs. The volume of generic
      tobramycin powder is more than 3.5 times the volume of proprietary tobramycin
      powder for a 1.2 g dose leading to the question: Does generic tobramycin elute
      from AL-PMMA faster than proprietary tobramycin? We performed elution studies on
      AL-PMMA beads made with 1.2 g of either generic tobramycin or proprietary
      tobramycin per batch of PMMA. Generic tobramycin eluted more than two times
      faster than proprietary tobramycin. The release mechanism started as dissolution
      driven zero-order release for the generic bead set but for the proprietary bead
      set the released mechanism started as anomalous diffusion. The release mechanism
      progressed to diffusion-driven first-order release in both. The increased volume
      of the generic tobramycin caused more tobramycin to be available for release. The
      increased elution of tobramycin associated with the greater volume of generic
      tobramycin powder could lead to clinically higher levels of tobramycin in wound
      fluid and local tissues; however, the higher volume of powder could potentially
      cause greater mechanical compromise of the PMMA.

PMID- 18340504
TI  - Human prolidase and prolidase deficiency: an overview on the characterization of
      the enzyme involved in proline recycling and on the effects of its mutations.
AB  - Here we summarized what is known at the present about function, structure and
      effect of mutations in the human prolidase. Among the peptidases, prolidase is
      the only metalloenzyme that cleaves the iminodipeptides containing a proline or
      hydroxyproline residue at the C-terminal end. It is relevant in the latest stage
      of protein catabolism, particularly of those molecules rich in imino acids such
      as collagens, thus being involved in matrix remodelling. Beside its intracellular
      functions, prolidase has an antitoxic effect against some organophosphorus
      molecules, can be used in dietary industry as bitterness reducing agent and
      recently has been used as target enzyme for specific melanoma prodrug activation.
      Recombinant human prolidase was produced in prokaryotic and eukaryotic hosts with
      biochemical properties similar to the endogenous enzyme and represents a valid
      tool both to better understand the structure and biological function of the
      enzyme and to develop an enzyme replacement therapy for the prolidase deficiency
      (PD). Prolidase deficiency is a rare recessive disorder caused by mutations in
      the prolidase gene and characterized by severe skin lesions. Single amino acid
      substitutions, exon splicing, deletions and a duplication were described as
      causative for the disease and are mainly located at highly conserved amino acids
      in the sequence of prolidase from different species. The pathophysiology of PD is
      still poorly understood; we offer here a review of the molecular mechanisms so
      far hypothesized.

PMID- 18340505
TI  - A case of periodic-fever-syndrome-like disorder with lipodystrophy, myositis, and
      autoimmune abnormalities.
AB  - A 24-year-old Japanese woman had been suffering from a periodic fever since 10
      months of age. She developed deformities in her fingers, with severe atrophy of
      subcutaneous adipose tissue, myositis, and frostbitten hands. She showed elevated
      C-reactive protein, creatine kinase, and gamma-globulin. She was also positive
      for antinuclear, anti-DNA, anti-SS-B, and anti-U1RNP antibodies. Her myositis was
      similar to amyopathic dermatomyositis rather than juvenile dermatomyositis.
      Although consanguineous marriage of her parents and early onset of disease
      suggested her disease as a hereditary disorder with periodic fever, her clinical
      feature and laboratory tests were unlike any known periodic fever syndromes. Her
      disease was regarded as a unique type of periodic-fever-syndrome-like disorder
      with autoimmune abnormalities.

PMID- 18340506
TI  - Preoperative steroid therapy stabilizes postoperative respiratory condition in
      myasthenia gravis.

PMID- 18340507
TI  - Mutations in the epidermal growth factor receptor gene and effects of EGFR
      tyrosine kinase inhibitors on lung cancers.
AB  - Epidermal growth factor receptor (EGFR) gene mutations are frequent in lung
      cancer arising in patients of Asian ethnicity, female sex, nonsmokers, and
      adenocarcinoma histology. About 70% of the patients with EGFR mutations respond
      to EGFR tyrosine kinase inhibitors (TKIs) including gefitinib and erlotinib,
      whereas only 10% of those without the mutations do so. Therefore, EGFR mutation
      is being recognized as one of the most reliable predictive factors for treatment
      using EGFR-TKIs. Another important issue in clinical practice is the fatal
      interstitial lung disease (ILD) that can develop in patients with gefitinib
      treatment, especially Asian patients. A nested case-control study recently
      conducted in Japan identified some risk factors that cause ILD, including age >
      or = 55 years, a history of smoking, preexisting ILD, poor performance status,
      short duration since diagnosis of lung cancer, reduced extent of normal lung on
      computed tomography, and concurrent cardiac disease. About half of the acquired
      resistance to EGFR-TKIs that almost always occurs during the course of treatment
      is caused by a secondary mutation at codon 790 (T790M). EGFR-TKIs are not
      universally effective for treating lung cancers but are effective in patients
      with particular genotypes. Therefore, patients who would benefit from EGFR-TKIs
      therapy should be concentrated in clinical trials. Based on this concept, Phase
      III clinical trials comparing gefitinib monotherapy with standard platinum-based
      chemotherapy are currently ongoing for patients with EGFR mutations and lung
      cancer.

PMID- 18340508
TI  - Single ventricle repair in children with Down's syndrome.
AB  - OBJECTIVE: There is a paucity of information regarding appropriate management of
      children with Down's syndrome and a functional single ventricle. We report the
      results of bidirectional superior cavopulmonary shunts in six patients with
      Down's syndrome with a functional single ventricle. METHODS: Between January 1991
      and December 2004, we identified six patients with Down's syndrome among 263 who
      had undergone bidirectional superior cavopulmonary shunts (BCPSs). There were
      four males and two females. The age at BCPS ranged from 1 to 12 years (mean 4.3
      +/- 3.9 years), and body weight varied between 8.2 and 29.4 kg (mean 13.8 +/- 7.8
      kg). All six patients had an unbalanced complete atrioventricular septal defect,
      with right ventricular hypoplasia present in five and left ventricular hypoplasia
      in one. RESULTS: There were no operative deaths, but one case required takedown
      of the BCPS. Except for this case, postoperative courses were generally
      uneventful. The median duration of follow-up was 46 months (range 12-80 months).
      Only two of five survivors after BCPS underwent a subsequent Fontan procedure,
      and one of these patients died of pulmonary hypertension post-operatively. The
      remaining three patients appeared to have significant risk factors for the Fontan
      procedure due to severe common atrioventricular valve regurgitation or persistent
      pulmonary vascular obstructive disease, including one who has completely dropped
      out from the Fontan track. CONCLUSION: Down's syndrome is a risk factor in
      patients with functionally single ventricle due to persistent pulmonary
      hypertension and airway obstruction. These results show that single ventricle
      repair in patients with Down's syndrome is accompanied with difficulties, and
      patient selection for the Fontan procedure should be done carefully.

PMID- 18340509
TI  - Off-pump coronary artery bypass grafting using in situ bilateral skeletonized
      internal thoracic arteries.
AB  - OBJECTIVE: All arterial off-pump coronary artery bypass grafting (OPCAB) with in
      situ bilateral skeletonized internal thoracic arteries (ITAs) may become a
      standard procedure that would provide better long-term results without affecting
      early results. METHODS: Our study included 404 consecutive patients who underwent
      OPCAB with one or two ITAs. We compared the clinical results of 135 patients who
      underwent OPCAB using unilateral ITA (UITA group) to those of 269 patients using
      bilateral ITAs (BITA group). RESULTS: The average number of distal anastomoses
      was 3.07 in the UITA group and 3.47 in the BITA group (P < 0.01). Four operative
      mortalities occurred in the UITA group and two in the BITA group. There were no
      significant differences in morbidity between the two groups. CONCLUSION: OPCAB
      using bilateral skeletonized ITAs is technically feasible, with good early
      results. Arterial OPCAB using in situ bilateral skeletonized ITAs may become a
      standard procedure in the future.

PMID- 18340510
TI  - Preoperative steroid therapy stabilizes postoperative respiratory conditions in
      myasthenia gravis.
AB  - OBJECTIVE: We reviewed our experience from 1990 to 2005 to examine whether
      control of myasthenia gravis (MG) with steroid therapy before surgery could
      stabilize postoperative respiratory conditions, compared with the nonsteroid
      treatment. METHODS: Records of 43 consecutive patients with MG who underwent
      extended thymectomy at Kansai Medical University Hospital were retrospectively
      reviewed. Two groups, a steroid group (n = 28) and a nonsteroid group (n = 15)
      were compared. RESULTS: In the steroid group, steroid doses ranged from 10 to 100
      mg every other day, or 40-60 mg daily. The patients showed significantly less
      thymus hyperplasia in the pathological findings (P = 0.023). Whereas 3 of 28 (7%)
      in the steroid group suffered respiratory insufficiency within 3 days of surgery,
      5 of 15 (33%) in the nonsteroid group exhibited the same problem (P = 0.030).
      Univariate analysis showed that steroid treatment was the only significant factor
      (P = 0.041) affecting respiratory insufficiency. Patients in the steroid group
      achieved palliation of MG more quickly after surgery than patients in the
      nonsteroid group (86% vs. 57% within 6 months, P = 0.059; 84% vs. 42% within 1
      year, P = 0.042). CONCLUSION: The control of myasthenia gravis with steroid
      therapy before surgery seems to stabilize postoperative respiratory status
      without having adverse effects on surgical infection.

PMID- 18340511
TI  - Results of video-assisted thoracoscopic surgery for esophageal cancer during the
      induction period.
AB  - OBJECTIVE: The attainment of proficiency in thoracoscopic radical esophagectomy
      for thoracic esophageal cancer requires much experience. We aimed to master this
      procedure safely with our regular surgical team members under the direction of an
      experienced surgeon. We evaluated the efficacy of instruction during the
      induction period and the significance of our results. METHODS: We compared the
      results of 12 thoracic esophageal cancer patients who underwent thoracoscopic
      radical esophagectomy in our institution (group A) to those of the initial 17
      patients who underwent the same operation at the director's institution (group
      B). RESULTS: We were able to perform complete thoracoscopic radical
      esophagectomies without any direction after experiencing 10 cases that were
      performed under adequate direction. The number of dissected lymph nodes and the
      duration of the procedure were similar in the two groups: 34 (22-53) vs. 26 (9
      55) nodes, P = 0.23; and 327.5 (230-455) vs. 315 (190-515) min, P = 0.947,
      respectively. The amount of thoracic blood loss was significantly less in group A
      than in group B: 185 (110-380) g vs. 440 (110-2360) g, P = 0.0035. Postoperative
      pneumonia and atelectasis were observed in 25.0% of group A patients and in 17.6%
      of group B patients. The incidence of recurrent nerve palsy was 30.7% in group A
      and 11.7% in group B, but there was no statistically significant difference (P =
      0.19). The morbidity rates in group A and group B were 41.6% and 29.4%,
      respectively (P = 0.694). CONCLUSION: Thoracoscopic radical esophagectomy can be
      mastered relatively quickly and safely under the direction of an experienced
      surgeon and a regular surgical team.

PMID- 18340512
TI  - Treatment of double carcinoma of the esophagus and lung.
AB  - We report four cases of double carcinoma of the esophagus and the lung. Case 1: a
      patient with synchronous double carcinoma of the esophagus and the lung underwent
      chemoradiotherapy (CRT) because of respiratory dysfunction. Case 2: a patient who
      was diagnosed with esophageal carcinoma after the surgery for lung carcinoma
      underwent CRT because of respiratory dysfunction. Case 3: a patient with
      synchronous double carcinoma underwent a two-stage operation. Case 4: a patient
      with synchronous double carcinoma underwent CRT at another hospital. To further
      treat the patients, we chose a two-stage operation. CRT is believed to be a
      feasible treatment in inoperable patients because patients 1 and 2 are alive 28
      and 21 months after CRT, respectively. A two-stage operation is considered a
      suitably safe surgical procedure because no fatal postoperative complications
      occurred in cases 3 and 4.

PMID- 18340513
TI  - Acute dissection of the innominate artery: a case of report.
AB  - A 61-year-old man developed a ruptured innominate artery associated with
      localized acute dissection. The innominate artery was reconstructed with a
      bifurcated prosthetic graft without brain complication.

PMID- 18340514
TI  - Blunt cardiac rupture in a patient with a history of total correction of
      tetralogy of Fallot.
AB  - A 35-year-old man with a history of total correction of tetralogy of Fallot (TOF)
      fell down while riding a bike and experienced blunt cardiac rupture. His vital
      signs were stable because the bleeding was limited by an adhesion caused by the
      previous operation. Chest computed tomography clearly displayed the ruptured
      points, and an emergency operation was performed. Because a pneumothorax was
      suspected, a cardiopulmonary bypass was established with a femorofemoral bypass
      while the patient was conscious before artificial ventilation was initiated. Two
      ruptured points were detected on the anterior wall of the right ventricle and
      were repaired by suturing. The patient recovered and was discharged without any
      major complications 40 days after the operation. This is the first published case
      of blunt cardiac rupture after total correction of TOF.

PMID- 18340515
TI  - Mitral valve repair for broad, asymmetrical prolapse in the posterior mitral
      leaflet.
AB  - We designed a mitral valve repair and successfully performed this repair for a
      case of broad, asymmetrical prolapse in the middle scallop of the posterior
      mitral leaflet. The repair procedure consists of making a fan-shaped leaflet by
      resecting the prolapsed portion in a trapezoid shape with detachment of the
      leaflet along the annulus and leaflet reapproximation by rotating this fan-shaped
      leaflet. This technique can utilize more leaflet tissue for filling the gap made
      by leaflet resection than the quadrangular resection and suture technique. As a
      result, it helps reduce tension on the suture lines, avoids the need for
      extensive annular plication, and also avoids leaflet distortion while making it
      easier to adjust the height of the leaflets that should be reapproximated. The
      essence of this mitral valve repair exists in the "resecting line of the
      leaflet," which has not yet been reported.

PMID- 18340516
TI  - Ride Safe: a child passenger safety program for American Indian/Alaska Native
      children.
AB  - BACKGROUND: In American Indian/Alaska Native (AI/AN) communities, child safety
      seat (CSS) use rates are much lower than in non-native communities. To reduce
      this disparity, Indian Health Service (IHS) staff developed, pilot-tested, and
      implemented Ride Safe, which provided education, training, and child safety seats
      for children aged 3-5 participating in Tribal Head Start Centers. METHODS: Focus
      groups, key informant interviews, and technical review guided program development
      and implementation. Progress reports and child safety seat use observations,
      conducted at the beginning and end of three program years (Fall 2003 to Spring
      2006), assessed program reach and impact. To examine CSS use, we used three
      multiple logistic regressions, including a conservative intent to treat analysis.
      RESULTS: Ride Safe reached approximately 3,500 children and their families at 14
      sites in six states, providing over 1,700 parents/family members with educational
      activities, 2,916 child safety seats, and child passenger safety (CPS) technician
      certification training for 78 Tribal staff. Children were 2.5 times (OR = 2.55, p
      < .01) as likely to be observed in child safety seats comparing Rounds 1 and 2
      data, with the most conservative model showing that the odds of being observed
      restrained were 74% higher (OR = 1.74, p = or<.01) after implementation of the
      program. CONCLUSIONS: The Ride Safe Program effectively increased child safety
      seat use in AI/AN communities, however, observed use rates ranging from 30% to
      71% remain well below the 2006 all US rate of 93%. Results from CSS educational
      and distribution/installation programs such as Ride Safe should be considered in
      light of the need to increase distribution programs and enhance enforcement
      activities in AI/AN communities, thereby reducing the disparity in AI/AN motor
      vehicle injuries and death.

PMID- 18340517
TI  - Tobacco use and cessation among pregnant Alaska Natives from Western Alaska
      enrolled in the WIC program, 2001-2002.
AB  - OBJECTIVES: This study examined the rate of tobacco use (cigarette smoking and
      smokeless tobacco [ST]) at three time points: during the 3 months before
      pregnancy, during pregnancy, and at 6 weeks postpartum among Alaska Native women
      residing in the Y-K Delta region of Western Alaska. METHODS: A retrospective, non
      randomized observational cohort design was utilized. The sample consisted of 832
      Alaska Natives (mean maternal age = 26.2 years, average length of gestation = 3.8
      months) seen at their first prenatal visit and enrolled in the women, infant, and
      children (WIC) program at the Yukon-Kuskokwim Delta Regional Hospital in Bethel,
      Alaska, during a 2-year-period (2001-2002). Tobacco use was assessed using an
      interview format at the first prenatal and at the 6-week postpartum visits.
      RESULTS: The rates of any tobacco use were 48% (95% CI 45%, 52%) 3 months before
      pregnancy, 79% (95% CI 76%, 82%) during pregnancy, and 70% (95% CI 67%, 74%) at 6
      weeks postpartum. The proportion of women using ST changed significantly (P <
      0.001) over the three time points (14%, 60%, and 61%, respectively) as well as
      the proportion of women who smoked cigarettes (P < 0.001) (40%, 42%, and 19%,
      respectively). CONCLUSIONS: This study documents the high rate of tobacco use,
      particularly ST use, during pregnancy among Alaska Native women. Development of
      tobacco use prevention and cessation interventions during pregnancy for Alaska
      Native women is warranted.

PMID- 18340518
TI  - Predictors of psychiatric symptoms in children with an autism spectrum disorder.
AB  - This study examined mental health risk/protective factors for DSM-IV psychiatric
      symptoms in children with an autism spectrum disorder (ASD) and their
      contribution to functioning separate from ASD symptom severity. Mothers/teachers
      completed measures of risk/protection and social, adaptive, and school
      functioning in 6- to 12-year-olds with a diagnosed ASD (N = 238). Bivariate
      correlations and simultaneous regression analyses indicated a unique pattern of
      predictors for attention-deficit/hyperactivity disorder, aggression, anxiety, and
      depression symptoms. Moreover, psychiatric symptoms differentially predicted
      social and school performance. Findings indicate that co-occurring psychiatric
      symptoms and their associated mental health risk/protective factors may have
      important clinical implications and generally support a biopsychosocial model of
      psychopathology in children with an ASD that appears to share many similarities
      with models for non ASD children.

PMID- 18340519
TI  - Recalled sex-typed behavior in childhood and sports' preferences in adulthood of
      heterosexual, bisexual, and homosexual men from Brazil, Turkey, and Thailand.
AB  - This research used interview and questionnaire data from homosexual (n = 177),
      bisexual (n = 157), and heterosexual (n = 544) men between 20 and 30 years of age
      among lower class men and university students in three countries: Brazil,
      Thailand, and Turkey. The main goal of the study was to examine the recalled
      childhood sex-typed behavior and adult sports preferences that distinguish
      homosexuals from bisexuals and heterosexuals. In all three cultures and both
      social groups, homosexual men were almost always more likely as children to have
      wanted to be a girl, to cross-dress, to play with girls, to do girls' tasks, and
      to practice fewer sports. They were also less likely to bully others or to engage
      in physical fights. As children, homosexual men were more likely to prefer
      swimming and playing volleyball rather than soccer and, as adults, they preferred
      watching gymnastics and swimming over soccer. The bisexuals scored intermediate
      mostly in "desire to be a girl" and "cross-dressing," although they were much
      closer to the heterosexuals. These results, coupled with previous cross-cultural
      research, suggest that cross-gender behavior in childhood may characterize most
      male homosexuals regardless of their cultural milieu.

PMID- 18340520
TI  - Relative finger lengths, sex differences, and psychological traits.
AB  - Various finger length and personality and ability measures were obtained for a
      sample of Australian adolescent twins (306 boys and 397 girls). A new measure of
      relative finger length (the length of a given finger relative to the sum of all
      four fingers) was investigated, and shown to be superior to the traditional 2D:4D
      for discriminating between the sexes. It also had the advantage of permitting a
      more analytic approach: for example, the 2nd finger-length contributed much more
      than the 4th finger length to the sex difference in 2D:4D, and a smooth gradient
      of sex differences across the hand was evident. Sex differences on right hands
      were greater than those for left hands. Within-sex correlations were obtained
      between the various finger-length measures and a personality and an ability scale
      that showed relatively large sex differences (Eysenck's Psychoticism scale and
      the spatial subscale from Jackson's Multidimensional Aptitude Battery). The
      correlations were low, but on the whole consistent with the between-sex
      differences for the girls. For the boys, this was so for Psychoticism, but
      spatial ability was, if anything, correlated in the opposite direction.

PMID- 18340522
TI  - Emotion processing in the visual brain: a MEG analysis.
AB  - Recent functional magnetic resonance imaging (fMRI) and event-related brain
      potential (ERP) studies provide empirical support for the notion that emotional
      cues guide selective attention. Extending this line of research, whole head
      magneto-encephalogram (MEG) was measured while participants viewed in separate
      experimental blocks a continuous stream of either pleasant and neutral or
      unpleasant and neutral pictures, presented for 330 ms each. Event-related
      magnetic fields (ERF) were analyzed after intersubject sensor coregistration,
      complemented by minimum norm estimates (MNE) to explore neural generator sources.
      Both streams of analysis converge by demonstrating the selective emotion
      processing in an early (120-170 ms) and a late time interval (220-310 ms). ERF
      analysis revealed that the polarity of the emotion difference fields was reversed
      across early and late intervals suggesting distinct patterns of activation in the
      visual processing stream. Source analysis revealed the amplified processing of
      emotional pictures in visual processing areas with more pronounced occipito
      parieto-temporal activation in the early time interval, and a stronger engagement
      of more anterior, temporal, regions in the later interval. Confirming previous
      ERP studies showing facilitated emotion processing, the present data suggest that
      MEG provides a complementary look at the spread of activation in the visual
      processing stream.

PMID- 18340523
TI  - Neuronal processes involved in subjective feeling emergence: oscillatory activity
      during an emotional monitoring task.
AB  - Subjective feeling, defined as the conscious experience of emotion and measured
      by self-report, is generally used as a manipulation check in studying emotional
      processes, rather than being the primary focus of research. In this paper, we
      report a first investigation into the processes involved in the emergence of a
      subjective feeling. We hypothesized that the oscillatory brain activity presumed
      to underlie the emergence of a subjective feeling can be measured by
      electroencephalographic (EEG) frequency band activity, similar to what has been
      shown in the literature for the conscious representation of objects. Emotional
      reactions were induced in participants using static visual stimuli. Episodes for
      which participants reported a subjective feeling were compared to those that did
      not lead to a conscious emotional experience, in order to identify potential
      differences between these two kinds of reactions at the oscillatory level.
      Discrete wavelet transforms of the EEG signal in gamma (31-63 Hz) and beta (15-31
      Hz) bands showed significant differences between these two types of reactions. In
      addition, whereas beta band activities were widely distributed, differences in
      gamma band activity were predominantly observed in the frontal and prefrontal
      regions. The results are interpreted and discussed in terms of the complexity of
      the processes required to perform the affective monitoring task. It is suggested
      that future work on coherent mental representation of multimodal reaction
      patterns leading to the emergence of conscious emotional experience should
      include modifications in the time window examined and an extension of the
      frequency range to be considered.

PMID- 18340524
TI  - Bridging science and practice in violence prevention: addressing ten key
      challenges.
AB  - This article illustrates ideas for bridging science and practice generated during
      the Division of Violence Prevention's (DVP) dissemination/implementation planning
      process. The difficulty of moving what is known about what works into broader use
      is near universal, and this planning process pushed us to look beyond the common
      explanations (e.g., providers were resistant/unwilling to change practice) and
      think about the multiple layers and systems involved. As part of this planning
      process, the Interactive Systems Framework for Dissemination and Implementation
      (ISF) was developed and then applied to the fields of child maltreatment and
      youth violence prevention. Challenges for each of the three systems in the ISF
      are discussed as well as and action and research ideas to address the challenges.
      Also described are actions taken by DVP in response to the planning process to
      illustrate how a funder can use the ISF to bridge science and practice.

PMID- 18340525
TI  - Proteasome inhibitor does not enhance MPTP neurotoxicity in mice.
AB  - Dysfunction of the proteasome function is known to be a potential mechanism for
      dopaminergic neuron degeneration. Here, we investigated to determine whether
      systematic administration of proteasome inhibitor, carbobenzoxy-L-gamma-t-butyl-L
      glutamyl-L-alanyl-L-leucinal (PSI), causes the increased susceptibility in 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. PSI was injected
      into MPTP-treated mice over a period of 2 weeks. Thereafter, we evaluated the
      effect of PSI 2, 4, and 8 weeks after the cessation of treatment with PSI. In the
      present study with HPLC analysis, PSI did not enhance MPTP-induced dopaminergic
      neurotoxicity in mice. Our present study with Western blot analysis also
      demonstrated that the reduction of tyrosine hydroxylase (TH) and glial fibrillary
      acidic protein (GFAP) protein levels in MPTP-treated mice was more pronounced
      than that in MPTP + PSI-treated animals. These results suggest that proteasome
      inhibitor did not enhance MPTP neurotoxicity in mice. Our findings suggest that
      proteasome inhibition is not a reliable model for PD. Thus, our findings provide
      further valuable information for the pathogenesis of Parkinson's disease.

PMID- 18340526
TI  - Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran
      exposure.
AB  - Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non
      cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays
      an important role in carbofuran neurotoxicity after sub-chronic exposure. The
      purpose of the present study is to evaluate the role of mitochondrial oxidative
      stress and dysfunction as a primary event responsible for neurotoxic effects
      observed after sub-chronic carbofuran exposure. Carbofuran was administered to
      rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant
      inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after
      28 days of carbofuran exposure. Mitochondrial respiratory chain functions were
      assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium
      bromide) reduction and activity of succinate dehydrogenase in isolated
      mitochondria. It was observed that carbofuran exposure significantly inhibited
      MTT reduction (31%) and succinate dehydrogenase activity (57%). This was
      accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols
      (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria
      isolated from carbofuran-exposed rat brain. The changes in mitochondrial
      oxidative stress and functions were associated with impaired cognitive and motor
      functions in the animals exposed to carbofuran as compared to the control
      animals. Based on these results, it is clear that carbofuran exerts its
      neurotoxicity by impairing mitochondrial functions leading to oxidative stress
      and neurobehavioral deficits.

PMID- 18340527
TI  - Validation of the Tenon breast cancer score for predicting non-sentinel lymph
      node status in breast cancer patients with sentinel lymph node metastasis: a
      prospective multicenter study.
AB  - BACKGROUND: Axillary lymph node dissection (ALND) is the standard treatment for
      patients with sentinel node (SN) metastasis, but most of these patients have
      negative non-sentinel nodes (non-SN). We have developed a scoring system (the
      Tenon score) to help identify a subgroup of patients who have a low risk of
      having non-SN metastases and who may thus forgo ALND. Here we validated the Tenon
      score in an independent cohort of SN-positive patients. PATIENTS AND METHODS: We
      tested the accuracy of the Tenon score for predicting non-SN status in a
      prospective multicenter study of 226 SN-positive breast cancer patients. We
      calculated the false-negative rate, sensitivity, specificity, and positive (PPV)
      and negative predictive values (NPV). Receiver operating characteristics (ROC)
      curves were constructed and the areas under the curve (AUC) were calculated as a
      measure of discriminatory capacity. RESULTS: At least one non-SN was positive in
      63 patients (27.9%). One hundred and twenty (53.1%) of the 226 patients had a
      Tenon score of 3.5 or less. Among these 120 patients, five had at least one
      positive non-SN. With a score cut-off of 3.5, the negative predictive value was
      95.8% and the false-negative rate was 4.2%. Overall, the Tenon score accurately
      predicted non-SN status, with an AUC of 0.82 (95% confidence interval, 0.77
      0.88). CONCLUSION: In this multicenter study of an independent patient
      population, the Tenon score was accurate and reproducible for predicting non-SN
      status in breast cancer patients. The simplicity and reliability of the variables
      on which the Tenon score is based may be an advantage over other scoring systems.

PMID- 18340528
TI  - Gene expression of topoisomerase II alpha (TOP2A) by microarray analysis is
      highly prognostic in estrogen receptor (ER) positive breast cancer.
AB  - INTRODUCTION: Overexpression of Topoisomerase II alpha (TOP2A) has been
      implicated with gene amplification of the 17q21 amplicon and consecutively with
      ErbB2 overexpression and amplification. However, gene amplification does not
      necessarily correlate with RNA and protein expression. There is growing evidence
      that TOP2A protein expression is a strong prognostic and TOP2A gene amplification
      might be a predictive marker (particularly for the use of anthracyclines).
      METHODS: Large scale analysis was performed using Affymetrix microarray data from
      n = 1,681 breast cancer patients to evaluate TOP2A expression. RESULTS: TOP2A
      expression showed a strong correlation with tumor size (chi(2)-test, P < 0.001),
      grading (P < 0.001), ErbB2 (P < 0.001) and Ki67 expression (P < 0.001) as well as
      nodal status (P = 0.042). Survival analysis revealed a significant prognostic
      value in ER positive (n = 994; log rank P < 0.001), but not in ER negative breast
      cancer patients (n = 369, P = 0.35). The prognostic impact of TOP2A expression
      was independent of Ki67 expression in ER positive tumors (P = 0.002 and P = 0.007
      for high and low Ki67, respectively). Moreover a worse prognosis of high TOP2A
      expressing tumors was found in the subgroup of ErbB2 negative tumors (P < 0.001)
      and a trend among ErbB2 positive tumors (P = 0.11). The prognostic value of TOP2A
      was independent of whether the patients were untreated or had received adjuvant
      therapy. In multivariate Cox regression analysis including standard parameters
      TOP2A emerged to be the top prognostic marker (HR 2.40, 95% CI 1.68-3.43, P <
      0.001). CONCLUSION: TOP2A expression is an independent prognostic factor in ER
      positive breast cancer and could be helpful for risk assessment in ER positive
      breast cancer patients.

PMID- 18340529
TI  - A prospective study of genetic polymorphism in MPO, antioxidant status, and
      breast cancer risk.
AB  - Oxidative stress may be involved in breast carcinogenesis. Myeloperoxidase (MPO)
      is an endogenous oxidant enzyme that generates reactive oxygen species (ROS). A
      single nucleotide polymorphism (SNP) G-463A in the promoter region has been
      associated with a decrease in risk of breast cancer. We assessed the association
      between this polymorphism and breast cancer risk in a nested case-control study
      within the Nurses' Health Study (1,269 incident breast cancer cases and 1,761
      matched controls). We further investigated potential gene-gene and gene
      environment interactions. There were no significant associations between MPO or
      COMT genotypes and risk of breast cancer. However, the combination of a priori
      hypothesized low-risk genotypes in MPO and COMT genes was associated with a
      marginally significant decrease in breast cancer risk (OR, 0.28; 95% CI, 0.08
      1.00). Dietary intake and plasma antioxidant levels may modify the association
      between the MPO polymorphism and breast cancer risk. Although the test for
      departure from multiplicative interaction was not significant, inverse
      associations with MPO genotype were more pronounced among women who consumed
      higher amounts of total fruits and vegetables (OR, 0.58; 95% CI, 0.30-1.12); this
      association was not found among the low-consumption group (OR, 1.11; 95% CI, 0.63
      1.96). The relative risk associated with the MPO homozygous variant genotype was
      0.44 (95% CI, 0.18-1.09) for women who had the highest level of plasma
      carotenoids. Results from this study suggest that exogenous and endogenous
      modulators of oxidative stress may modify the association between the MPO
      polymorphism and breast cancer risk. Further research is needed to confirm these
      possible associations.

PMID- 18340530
TI  - BRCA1 2080insA mutation in familial breast cancer.

PMID- 18340531
TI  - Tenoxicam modulates antioxidant redox system and lipid peroxidation in rat brain.
AB  - We investigated effects of two doses of Tenoxicam, a type 2 cyclooxygenase
      inhibitor, administration on lipid peroxidation and antioxidant redox system in
      cortex of the brain in rats. Twenty-two male Wistar rats were randomly divided
      into three groups. First group was used as control. 10 and 20 mg/kg body weight
      Tenoxicam were intramuscularly administrated to rats constituting the second and
      third groups for 10 days, respectively. Both dose of Tenoxicam administration
      resulted in significant increase in the glutathione peroxidase activity, reduced
      glutathione and vitamins C and E of cortex of the brain. The lipid peroxidation
      levels in the cortex of the brain were significantly decreased by the
      administration. Vitamin A and beta-carotene concentration was not affected by the
      administration. There was no statistical difference in all values between 10 and
      20 mg Tenoxicam administrated groups. In conclusion, treatment of brain with 10
      and 20 mg Tenoxicam has protective effects on the oxidative stress by inhibiting
      free radical and supporting antioxidant redox system.

PMID- 18340532
TI  - Obstructive defecation in middle-aged women.
AB  - Obstructive defecation, a significant contributor to constipation, is frequently
      reported in middle-aged women, yet few population-based studies have established
      prevalence in this group. We analyzed data from the Reproductive Risks for
      Incontinence Study at Kaiser, a population-based cohort of racially diverse
      women, 40-69 years old, to describe the prevalence of obstructive defecation and
      identify associated risk factors. The Reproductive Risks for Incontinence Study
      at Kaiser is a randomly selected cohort of 2,109 women in the Kaiser Medical
      System. Obstructive defecation, determined by self-report, was defined as
      difficulty in passing stool, hard stool, straining for more than 15 min, or
      incomplete evacuation, occurring at least weekly. Age, race, income, education,
      drinking, health status, parity, pelvic organ prolapse, urinary incontinence,
      number of medications, hysterectomy, surgery for pelvic organ prolapse,
      colectomy, irritable bowel syndrome, and body mass index were assessed for both
      their univariate and multivariate association with obstructive defecation.
      Multivariate logistic regression was used to determine the independent
      association between associated factors and the primary outcome of obstructive
      defecation. Obstructive defecation that occurred at least weekly was reported by
      12.3% of women. Significant independent risk factors included irritable bowel
      syndrome [odds ratio 1.78, (95% confidence interval 1.21-2.60)], vaginal or
      laparoscopic hysterectomy [2.01 (1.15-3.54)], unemployment [2.33 (1.39-3.92)],
      using three or more medications [1.81 (1.36-2.42)], symptomatic pelvic organ
      prolapse [2.34 (1.47-3.71)], urinary incontinence surgery [2.52 (1.29-4.90)], and
      other pelvic surgery [1.35 (1.03-1.78)]. We concluded that obstructive defecation
      is common in middle-aged women, especially those with a history of treatment for
      pelvic floor conditions. Women who had undergone laparoscopic/vaginal
      hysterectomies or surgery for pelvic organ prolapse or urinary incontinence had a
      nearly two times greater risk of weekly obstructive defecation. Demographic
      factors, with the exception of employment status, were not significant,
      indicating that obstructive defecation, although widespread, does not affect any
      particular group of women.

PMID- 18340533
TI  - Developing a culturally competent peer support intervention for Spanish-speaking
      Latinas with breast cancer.
AB  - Little research exists on the need for, barriers to, and acceptability and
      effectiveness of psychosocial support services among Latinas with breast cancer,
      despite their increased risks of psychosocial distress. This formative research
      study identifies barriers to and benefits and components of an effective peer
      support counselor intervention for Spanish-speaking Latinas recently diagnosed
      with breast cancer. Analysis was based on interviews of 89 Latino cancer patients
      referred to psychosocial services; 29 Spanish-speaking survivors of breast
      cancer; and 17 culturally competent advocates for Latinos with cancer. Results
      indicate that interventions should begin close to diagnosis; build self-care
      skills; be culturally competent and emotionally supportive; provide language
      appropriate cancer information; encourage self-expression; and address lack of
      access to and knowledge of services. Creating such psychosocial programs with
      input from survivors and advocates who have similar self-identities to patients
      would improve quality of life in diverse and underserved populations.

PMID- 18340534
TI  - Effect of biopolymers on structure of hydroxyapatite and interfacial interactions
      in biomimetically synthesized hydroxyapatite/biopolymer nanocomposites.
AB  - The interfacial interaction and effect of biopolymer on crystal structure of
      hydroxyapatite in biomimetically synthesized nanocomposites,
      chitosan/hydroxyapatite (ChiHAP50), polygalacturonic acid/hydroxyapatite
      (PgAHAP50), and chitosan/polygalacturonic acid/hydroxyapatite (ChiPgAHAP50) have
      been investigated using atomic force microscopy (AFM), Fourier transform infrared
      (FTIR) spectroscopy, and Rietveld analysis. AFM phase images show nano-sized
      hydroxyapatite particles uniformly distributed in biopolymer. FTIR spectra
      indicate that chitosan interacts with hydroxyapatite through NH(3)(+) groups,
      whereas in polygalacturonic acid/hydroxyapatite, dissociated carboxylate groups
      (COO(-)) form unidentate chelate with calcium atoms. A change in lattice
      parameters of hydroxyapatite in all nanocomposites is observed using Rietveld
      analysis. The increase in lattice parameters was most prominent along c-axis in
      ChiHAP50 and ChiPgAHAP50 nanocomposites, which was 0.388% and 0.319%,
      respectively. Comparison between particle sizes of hydroxyapatite, determined
      from AFM and Rietveld analysis, indicates presence of amorphous phase in
      hydroxyapatite particles, which is believed to be present at the interface of
      hydroxyapatite and biopolymer.

PMID- 18340535
TI  - Impact of positive end-expiratory pressure during heterogeneous lung injury:
      insights from computed tomographic image functional modeling.
AB  - Image Functional Modeling (IFM) synthesizes three dimensional airway networks
      with imaging and mechanics data to relate structure to function. The goal of this
      study was to advance IFM to establish a method of exploring how heterogeneous
      alveolar flooding and collapse during lung injury would impact regional
      respiratory mechanics and flow distributions within the lung at distinct positive
      end-expiratory pressure (PEEP) levels. We estimated regional respiratory system
      elastance from computed tomography (CT) scans taken in 5 saline-lavaged sheep at
      PEEP levels from 7.5 to 20 cmH(2)O. These data were anatomically mapped into a
      computational sheep lung model, which was used to predict the corresponding
      impact of PEEP on dynamic flow distribution. Under pre-injury conditions and
      during lung injury, respiratory system elastance was determined to be spatially
      heterogeneous and the values were distributed with a hyperbolic distribution in
      the range of measured values. Increases in PEEP appear to modulate the
      heterogeneity of the flow distribution throughout the injured lung. Moderate
      increases in PEEP decreased the heterogeneity of elastance and predicted flow
      distribution, although heterogeneity began to increase for PEEP levels above 12.5
      15 cmH(2)O. By combining regional respiratory system elastance estimated from CT
      with our computational lung model, we can potentially predict the dynamic
      distribution of the tidal volume during mechanical ventilation and thus identify
      specific areas of the lung at risk of being overdistended.

PMID- 18340536
TI  - The evolution of extracranial approaches to the pituitary and anterior skull
      base.
AB  - The development of extracranial approaches to the anterior skull base has been a
      process in development for over a 100 years. Many neurosurgical (and non
      neurosurgical) pioneers have contributed to its evolution. In this paper, we will
      review the major contributors and contributions to this evolving field.

PMID- 18340537
TI  - Greater drug injecting risk for HIV, HBV, and HCV infection in a city where
      syringe exchange and pharmacy syringe distribution are illegal.
AB  - Comparing drug-injecting risk between cities that differ in the legality of
      sterile syringe distribution for injection drug use provides a natural experiment
      to assess the efficacy of legalizing sterile syringe distribution as a structural
      intervention to prevent human immunodeficiency virus (HIV) and other parenterally
      transmitted infections among injection drug users (IDUs). This study compares the
      parenteral risk for HIV and hepatitis B (HBV) and C (HCV) infection among IDUs in
      Newark, NJ, USA, where syringe distribution programs were illegal during the
      period when data were collected, and New York City (NYC) where they were legal.
      IDUs were nontreatment recruited, 2004-2006, serotested, and interviewed about
      syringe sources and injecting risk behaviors (prior 30 days). In multivariate
      logistic regression, adjusted odds ratios (AOR) and 95% confidence intervals (95%
      CI) for city differences are estimated controlling for potential city
      confounders. IDUs in Newark (n = 214) vs. NYC (n = 312) were more likely to test
      seropositive for HIV (26% vs. 5%; AOR = 3.2; 95% CI = 1.6, 6.1), antibody to the
      HBV core antigen (70% vs. 27%; AOR = 4.4; 95% CI = 2.8, 6.9), and antibody to HCV
      (82% vs. 53%; AOR = 3.0; 95% CI = 1.8, 4.9), were less likely to obtain syringes
      from syringe exchange programs or pharmacies (AOR = 0.004; 95% CI = 0.001, 0.01),
      and were more likely to obtain syringes from street sellers (AOR = 74.0; 95% CI =
      29.9, 183.2), to inject with another IDU's used syringe (AOR = 2.3; 95% CI = 1.1,
      5.0), to reuse syringes (AOR = 2.99; 95% CI = 1.63, 5.50), and to not always
      inject once only with a new, sterile syringe that had been sealed in a wrapper
      (AOR = 5.4; 95% CI = 2.9, 10.3). In localities where sterile syringe distribution
      is illegal, IDUs are more likely to obtain syringes from unsafe sources and to
      engage in injecting risk behaviors. Legalizing and rapidly implementing sterile
      syringe distribution programs are critical for reducing parenterally transmitted
      HIV, HBV, and HCV among IDUs.

PMID- 18340539
TI  - Introduction to the second special issue of Medical Geology in developing
      countries; a collaboration between SEGH and International Medical Geology
      Association (IMGA).

PMID- 18340538
TI  - Characterization of new hAT transposable elements in 12 Drosophila genomes.
AB  - In silico searches for sequences homologous to hAT elements in 12 Drosophila
      genomes have allowed us to identify 37 new hAT elements (8 in D. ananassae, 11 in
      D. mojavensis, 2 in D. sechellia, 1 in D. simulans, 2 in D. virilis, 3 in D.
      yakuba, 3 in D. persimilis, 1 in D. grimshawi, 5 in D. willistoni and 1 in D.
      pseudobscura). The size of these elements varies from 2,359 to 4,962 bp and the
      terminal inverted repeats (TIRs) show lengths ranging from 10 to 24 bp. Several
      elements show intact transposase ORFs, suggesting that they are active. Conserved
      amino acid motifs were identified that correspond to those important for
      transposase activity. These elements are highly variable and phylogenetic
      analysis showed that they can be clustered into four different families.
      Incongruencies were observed between the phylogenies of the transposable elements
      and those of their hosts, suggesting that horizontal transfer may have occurred
      between some of the species.

PMID- 18340540
TI  - Multicenter evaluation of noninvasive cardiac output measurement by bioreactance
      technique.
AB  - OBJECTIVES: Bioreactance, the analysis of intrabeat variations in phase of a
      transthoracic voltage in response to an applied high frequency transthoracic
      current, was recently introduced for noninvasive cardiac output measurement
      (NICOM). We evaluated NICOM compared to thermo- dilution (TD) in several clinical
      settings. METHODS: 111 patients with a clinical indication for TD cardiac output
      (CO) measurement were recruited at five centers, including patients in cardiac
      catheterization laboratories, cardiac care units and intensive care units. CO
      measurements were made simulta- neously with TD and the bioreactance method and
      compared by regression analysis. RESULTS: For studies in the intensive care
      units, TD-based CO and NICOM were highly correlated (r = 0.78, P < 0.0001) and
      did not differ significantly from each other (P = 0.55). Results in the cardiac
      catheterization laboratory were similar (r = 0.71, P < 0.001; P = 0.28 NICOM
      versus TD). In subsets of patients, NICOM was shown to be better corre- lated
      with TD-CO than CO obtained with the Fick method or with standard bioimpedance
      based measurements of CO. CONCLUSIONS: On average, compared to TD, bioreactance-
      based NICOM has acceptable accuracy in challenging clinical environments.
      Availability of such a tool may allow clinicians to have information about CO in
      patients where this information is not currently available to help diagnosis and
      guide therapy.

PMID- 18340541
TI  - Malignant melanoma risk after exposure to fertility drugs: results from a large
      Danish cohort study.
AB  - OBJECTIVE: The aim was to examine the effects of fertility drugs on malignant
      melanoma risk using data from the largest cohort of infertile women to date.
      METHODS: A cohort of 54,362 women with infertility problems referred to Danish
      fertility clinics in the period 1963-1998 was established. A detailed data
      collection including information about type and amount of treatment was
      conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of
      malignant melanoma associated with different fertility drugs after adjustment for
      parity status. RESULTS: 112 malignant melanomas were identified during follow-up
      through 2000. Use of clomiphene, gonadotrophins, hCG or GnRH did not affect risk
      of malignant melanoma significantly. When stratifying for parity, however, use of
      gonadotrophins (RR = 2.29; CI: 1.16-4.52) or GnRH (RR = 3.26; 95% CI: 1.50-7.09)
      among parous women was associated with a significant increased risk. For all
      groups of fertility drugs, we found no association with number of cycles of use
      or years since first use (latency). CONCLUSIONS: Our findings showed no strong
      association between malignant melanoma risk and use of fertility drugs, although
      the results indicated that use of gonadotrophins or GnRH might increase risk in
      parous women. Longer follow-up is needed to confirm our findings.

PMID- 18340542
TI  - Hormonal profile of diabetic men and the potential link to prostate cancer.
AB  - OBJECTIVE: Previous studies suggest men with diabetes may be at reduced risk for
      prostate cancer as compared to men without diabetes. To investigate potential
      biological mechanisms, hormonal profiles of diabetic men and non-diabetic
      controls were compared. METHODS: In the Health Professionals Follow-Up Study,
      plasma levels of C-peptide, testosterone, sex-hormone binding globulin, insulin
      like growth factor-1, and insulin-like growth factor binding protein-3 were
      determined in 171 diabetic men and 3,001 non-diabetic controls. Multiple linear
      regression analysis was conducted and least square means were calculated for
      hormones of interest. RESULTS: Plasma levels of several hormones either < or =1,
      1.1-6, 6.1-14.9, or > or =15 years after diagnosis with diabetes were examined.
      As time since diabetes diagnosis increased, plasma levels of C-peptide and IGFBP
      3 significantly decreased (p for trend: C-peptide =.05, IGFBP-3 =.03). While
      testosterone and SHBG levels both significantly increased with increasing time
      since diabetes diagnosis (p for trend: testosterone =.02, SHBG =.002), the ratio
      of testosterone to SHBG decreased, suggesting a reduction in bioavailable
      testosterone. Plasma IGF-1 levels were lower in diabetics than non-diabetics, but
      no significant time trend was noted. CONCLUSION: This study of hormonal profiles
      of diabetic versus non-diabetic men identified changes in diabetic men that may
      be consistent with reduced prostate cancer risk.

PMID- 18340543
TI  - Environmental contaminants in Canadian shorebirds.
AB  - Canadian shorebirds are exposed to environmental contaminants throughout their
      annual cycle. Contaminant exposure among species varies with diet, foraging
      behaviour and migration patterns. We sampled twelve species of shorebirds from
      four locations across Canada to assess their exposure to PCBs, organochlorine
      pesticides, as well as four trace elements (Hg, Se, Cd, As). SigmaPCB and
      SigmaDDT followed by SigmaCHL were most frequently found above trace level in the
      shorebird carcasses. In general, the plover species (American golden,
      semipalmated, black-bellied) appear to be the most contaminated with
      organochlorines, whereas Hudsonian and marbled godwits appear to be the least
      contaminated. Among adult birds, the greater and lesser yellowlegs had the
      highest hepatic Hg concentrations (2.4-2.7 microg g(-1) dw), whereas American
      golden plovers as well as Hudsonian and marbled godwits contained relatively low
      levels of Hg (<1 microg g(-1) dw). Renal Se concentrations varied from 3.2 to
      16.7 microg g(-1) dw and exhibited little interspecific or seasonal variation.
      Renal Cd levels in adult birds were highest in Hudsonian godwits from Quill Lakes
      (43 microg g(-1) dw) and Cape Churchill (12 microg g(-1) dw), and lowest (0.8-1.5
      microg g(-1) dw) in greater and lesser yellowlegs from Cape Churchill and Bay of
      Fundy. Renal As concentrations varied from 0.06 microg g(-1) dw in golden plovers
      from Cape Churchill to 4.6 and 5.1 microg g(-1) dw in dunlin samples from the
      Pacific coast. There is no evidence that contaminants were adversely affecting
      the shorebirds sampled from the Canadian locations in this study.

PMID- 18340544
TI  - Cloning, characterization and expression of the extracellular lipase gene from
      Aureobasidium pullulans HN2-3 isolated from sea saltern.
AB  - The extracellular lipase structural gene was isolated from cDNA of Aureobasidium
      pullulans HN2-3 by using SMART(TM) RACE cDNA amplification kit. The gene had an
      open reading frame of 1245 bp long encoding a lipase. The coding region of the
      gene was interrupted by only one intron (55 bp). It encodes 414 amino acid
      residues of a protein with a putative signal peptide of 26 amino acids. The
      protein sequence deduced from the extracellular lipase structural gene contained
      the lipase consensus sequence (G-X-S-X-G) and three conserved putative N
      glycosylation sites. According to the phylogenetic tree of the lipases, the
      lipase from A. pullulans was closely related to that from Aspergillus fumigatus
      (XP_750543) and Neosartorya fischeri (XP_001257768) and the identities were 50%
      and 52%, respectively. The mature peptide encoding cDNA was subcloned into pET
      24a (+) expression vector. The recombinant plasmid was expressed in Escherichia
      coli BL21(DE3). The expressed fusion protein was analyzed by SDS-PAGE and western
      blotting and a specific band with molecular mass of about 47 kDa was found.
      Enzyme activity assay verified the recombinant protein as a lipase. A maximum
      activity of 0.96 U/mg was obtained from cellular extract of E. coli BL21(DE3)
      harboring pET-24a(+)LIP1. Optimal pH and temperature of the crude recombinant
      lipase were 8.0 and 35 degrees C, respectively and the crude recombinant lipase
      had the highest hydrolytic activity towards peanut oil.

PMID- 18340545
TI  - Secretion pathway for the poly(3-hydroxybutyrate) depolymerase in Ralstonia
      pickettii T1.
AB  - The extracellular poly(3-hydroxybutyrate) depolymerase from Ralstonia pickettii
      T1 has been purified, its function and character investigated in detail, and its
      gene cloned and sequenced. However, the mechanism by which this enzyme is
      secreted has not been elucidated. A mutant unable to degrade poly(3
      hydroxybutyrate), N17, was obtained with the random insertion of a mini
      transposon, Tn5. Western analysis using antiserum against the poly(3
      hydroxybutyrate) depolymerase of Ralstonia pickettii T1, revealed that N17
      accumulated the poly(3-hydroxybutyrate) depolymerase in the periplasm and
      cytoplasm, and did not secrete the enzyme into the external medium. It was also
      found that 3-hydroxybutyrate-oligomer hydrolase was secreted but inactive. The
      disrupted gene in N17, depO, was analyzed by Southern hybridization and its
      nucleotide sequence was determined. One complete open reading frame was found in
      the cloned 2.3-kbp DNA fragment. From a BLAST search, this gene product was found
      to be homologous to PulO of Ralstonia eutropha JMP134 (60% identity) and XcpA of
      Pseudomonas aeruginosa (60% identity). These proteins are prepilin peptidase/N
      metyltransferases, a component of the Type II secretion pathway. DepO also had
      the four cysteines highly conserved in most prepilin peptidases at the same
      positions. The transcript of depO was examined by Northern hybridization using
      depO as a probe. In the total RNA of Ralstonia pickettii T1 in the early
      stationary phase, a band at 2.6-kb was detected, suggesting depO to be a
      functional gene. In this study, it was found that poly(3-hydroxybutyrate)
      depolymerase was secreted by the Type II pathway.

PMID- 18340546
TI  - A case of Cunninghamella bertholettiae rhino-cerebral infection in a leukaemic
      patient and review of recent published studies.
AB  - Cunninghamella bertholletiae infection occurs most frequently in neutropenic
      patients affected by haematological malignancies, is associated with an
      unfavourable outcome. We report a case of rhino-mastoidal fungal infection in a
      leukaemic patient. Bioptical tissue cultures yield the isolation of a mould with
      typical properties of Cunninghamella species. Liposomal amphotericin B (L-Amb)
      therapy combined with surgical intervention brought the lesion to recovery.
      Nevertheless, the patient died 14 days after bone marrow transplantation (BMT)
      from bacterial sepsis. Mastoiditis was documented at CT-scan. The conditioning
      regimen probably caused the reactivation of the Cunninghamella infection that led
      to the patient's fatal outcome; fungal hyphae were detected after autopsy of
      brain and lung tissue.

PMID- 18340547
TI  - In vitro inhibition of oral Candida albicans by chicken egg yolk antibody (IgY).
AB  - This study was conducted to measure Candida albicans-specific chicken egg yolk
      antibody (IgY) inhibition of fluconazole-sensitive and resistant strains of C.
      albicans in order to assess potential use in the prevention and treatment of oral
      candidiasis. In this study, laying hens were immunized, and IgY was extracted by
      water dilution. The Minimal Inhibitory Concentrations (MICs) of IgY for
      inhibiting C. albicans growth were determined using the broth microdilution
      method from the CLSI M27-A2 protocol. Fluconazole (FLC) was used as the control.
      The results were analyzed with the chi(2) test. The anti-Candida titer of anti-C.
      albicans IgY was 1:12,000. The concentration of the IgY extract that effectively
      inhibited the growth of C. albicans was between 1.25 g/l and 5.0 g/l, and the
      efficacy rate was 82.98% during the observed 24-48 h time period. No correlation
      was recorded between the drug resistance of FLC and growth inhibition by IgY. It
      was concluded that anti-C. albicans IgY inhibited the growth of C. albicans in
      vitro and there was no correlation between the drug resistance of FLC and the
      growth inhibition by IgY (P > 0.99).

PMID- 18340548
TI  - Domain II hairpin structure in ITS1 sequences as an aid in differentiating
      recently evolved animal and plant pathogenic fungi.
AB  - The hypothesis that ITS structural features can be used to define fungal groups,
      where sequence analysis is unsatisfactory, was examined in plant and animal
      pathogenic fungi. Structural models of ITS1 regions were predicted for presumed
      closely related species in Colletotrichum and Trichophyton anamorphs of
      Arthroderma species. Structural alignment of models and comparison with ITS
      sequence analysis identified a variable region in a conserved hairpin formed from
      a common inverted repeat. Thirteen different hairpin structure models were
      obtained for Colletotrichum species and five different models were obtained for
      Trichophyton species. The different structure types could be matched to
      individual species and species complexes as defined by ITS sequence analysis.

PMID- 18340549
TI  - Epidermal growth factor receptors: function modulation by phosphorylation and
      glycosylation interplay.
AB  - Post-translational modifications (PTMs) of proteins induce structural and
      functional changes that are most often transitory and difficult to follow and
      investigate in vivo. In silico prediction procedures for PTMs are very valuable
      to foresee and define such transitory changes responsible for the
      multifunctionality of proteins. Epidermal growth factor receptor (EGFR) is such a
      multifunctional transmembrane protein with intrinsic tyrosine kinase activity
      that is regulated primarily by ligand-stimulated transphosphorylation of
      dimerized receptors. In human EGFR, potential phosphorylation sites on Ser, Thr
      and Tyr residues including five autophosphorylation sites on Tyr were
      investigated using in silico procedures. In addition to phosphorylation, O-GlcNAc
      modifications and interplay between these two modifications was also predicted.
      The interplay of phosphorylation and O-GlcNAc modification on same or neighboring
      Ser/Thr residues is termed as Yin Yang hypothesis and the interplay sites are
      named as Yin Yang sites. Amongst these modification sites, one residue is
      localized in the juxtamembrane (Thr 654) and two are found in the catalytic
      domain (Ser 1046/1047) of the EGFR. We propose that, when EGFR is O-GlcNAc
      modified on Thr 654, EGFR may be transferred from early to late endosomes,
      whereas when EGFR is O-GlcNAc modified on Ser 1046/1047 desensitization of the
      receptor may be prevented. These findings suggest a complex interplay between
      phosphorylation and O-GlcNAc modification resulting in modulation of EGFR's
      functionality.

PMID- 18340550
TI  - Fluorescent in-situ hybridization of cattle and sheep chromosomes with cloned
      human fragile-X DNA.
AB  - An extensive study on spontaneous and 5-Fluorodeoxyuridine induced fragile sites
      identified Xq31 in cattle (Bos taurus) and (Xq24, Xq26) in sheep (Ovis aries) in
      addition to several autosomal fragile sites (under publication). A ZOO-FISH study
      using three cloned human fragile-X probes with CCG/CGG(n) trinucleotide repeat
      sequence was carried out to determine homology between human and bovine fragile
      X. The hybridisation results showed only a weak signal on a human chromosome that
      was not an X with all three fragile site probes. No signals were detected in
      sheep chromosomes. The signal of all three human fragile-X probes on cattle
      chromosomes was however, medium-prominent sub-centromeric signal on two
      homologues. BrdU administration in 12 h before harvesting identified these
      homologues to be chromosome number 5. In addition retrospective slides of cattle
      and sheep chromosomes used for fragile site studies showed no signals whatsoever.
      It was therefore concluded that no homology existed between human and bovine
      fragile-X.

PMID- 18340551
TI  - Heat resistance of allograft tissue.
AB  - Lyophilized allograft musculoskeletal tissue is generally intended to be stored
      at "ambient" or "room" temperature, and usually is kept in climate controlled
      indoor storage areas. However, there is a question of what temperature extremes
      tissue may see, especially during transportation, in that these extremes may
      exceed even the limits of "ambient" conditions. Temperatures may become quite
      hot, but only for a few hours and only during daytime. Damage from high
      temperatures, if it occurs, is expected to be evident by damage to the collagen
      component of bone, soft tissue, and demineralized bone, as well as to the growth
      factors contained in demineralized bone. If damage is significant, then
      temperature monitoring requirements for lyophilized allograft tissue might be
      necessary. To answer this question, a literature review was carried out to look
      at the short-term temperature resistance of collagen and demineralized bone. Both
      collagen and the growth factors in demineralized bone show remarkable short term
      tolerance to elevated temperatures in the dry state, and it was concluded that
      temperature excursions of 50 degrees C or less, lasting for a few days or less,
      would not cause any significant deterioration. This means that temperature
      monitoring also should not be required.

PMID- 18340552
TI  - Matrilysin inhibits proliferation and modulates sensitivity of lung cancer cells
      to FasL-mediated apoptosis.
AB  - AIMS AND BACKGROUND: Matrix metalloproteinase (MMP) family member MMP-7
      (matrilysin) cleaves various cell-surface proteins to alter their effector
      functions in addition to a broad substrate specificity against extracellular
      matrix components. Matrilysin expression is closely associated with the advanced
      clinicopathological stages and unfavorable prognosis. The current study tried to
      describe the comprehensive impacts of matrilysin on proliferation, and focused on
      its influence on the susceptibility to FasL-induced apoptosis in A549 lung
      adenocarcinoma cell line. We also detected the expressions of apoptosis-relative
      genes to further clarify the underlying mechanisms. STUDY DESIGN: The viability
      of A549 cells was determined by MTT and the apoptosis was assessed by Hoechst
      33342 staining and Annexin V-FITC/PI apoptosis kit. The expressions of apoptosis
      relative genes were evaluated by flow cytometry, ELISA, and real-time
      quantitative RT-PCR, respectively. RESULTS: Overall, matrilysin exhibited the
      inhibition of cell growth in a dose- and time-dependent manner by arresting in
      G0/G1 phase of the cell cycle and inducing apoptosis on A549 cells. Although it
      directly promoted apoptosis at high concentrations, a certain range of matrilysin
      might protect tumor cells from FasL-mediated death. The underlying mechanism may
      be due to the imbalance in the susceptibility of surface membrane-bound Fas
      receptor and ligand to proteolysis activity of matrilysin. CONCLUSION: Our data
      indicated matrilysin may be multiple, multifarious, and multifaceted functions
      contributing to early tumor growth. A therapeutic key might be to modulate
      activity and function of matrilysin under diverse pathological conditions, but
      not completely eliminate the expression or function.

PMID- 18340553
TI  - Factors associated with the presence of drug-resistant bacteria and recurrent
      acute otitis media in children--a study in a private clinic.
AB  - CONCLUSIONS: The proportion of drug-resistant bacteria was lower than previous
      reports. In children with acute otitis media (AOM), lower age, presence of
      multiple bacteria, and otitis media with effusion (OME) represented significant
      factors for recurrent AOM and the presence of drug-resistant bacteria. OBJECTIVE:
      Recently, the proportion of drug-resistant bacteria has been increasing in
      children with AOM. We studied the proportion of drug-resistant bacteria and
      background factors for detection of drug-resistant bacteria and recurrent AOM in
      a private clinic. SUBJECTS AND METHODS: Subjects comprised 170 patients <12 years
      old with AOM. Middle ear fluid was collected and pathogenic bacteria were
      identified. The following factors were considered: age, sex, use of antibiotics
      in the past 1 month, past history of recurrent AOM, presence of OME, and multiple
      bacteria of the three main strains (Streptococcus pneumoniae, Haemophilus
      influenzae, and Moraxella catarrhalis). RESULTS: A total of 169 strains were
      detected in 77% of children with AOM. Drug-resistant bacteria comprised 44 of the
      169 strains (26%). Lower age (p=0.001) and presence of multiple bacteria
      (p<0.001) represented significant factors for the presence of drug-resistant
      bacteria. OME was a significant factor for recurrent AOM (p<0.001).

PMID- 18340554
TI  - Changes in auditory behaviors of multiply handicapped children with deafness
      after hearing aid fitting.
AB  - CONCLUSION: The early diagnosis of deafness and the early fitting of hearing aids
      in multiply handicapped children are recommended for language development in
      these children even when their neurological or mental status is poor. SUBJECTS
      AND METHODS: The subjects consisted of 5 hearing-impaired infants with no other
      problems and 28 hearing-impaired children with multiple handicaps. Behavioral
      audiometry and auditory brainstem responses were used for evaluating hearing
      impairment. The 5 hearing-impaired infants with no other problems underwent
      hearing aid fitting at approximately 1 year of age and the 28 hearing-impaired
      children with multiple handicaps underwent hearing aid fitting at various times
      from 1 to 5 years of age. The effects of their hearing aids were compared on the
      basis of auditory behavioral changes. The developmental scale of auditory
      behaviors in infancy that we proposed was introduced to evaluate the development
      of auditory behaviors. RESULTS: The auditory behaviors of the hearing-impaired
      children with no other problems showed constant changes with age after hearing
      aid fitting. However, among the 28 hearing-impaired children with multiple
      handicaps, 17 showed improvement in auditory behaviors, 5 showed no improvement
      in auditory behaviors because of the associated severe motor and mental
      retardation, and epilepsy, and 6 were unable to adapt to wearing hearing aids.

PMID- 18340555
TI  - Isolated hearing loss associated with T7511C mutation in mitochondrial DNA.
AB  - CONCLUSION: The T7511C mutation is considered responsible for maternally
      inherited, isolated sensorineural hearing loss of cochlear origin. This mutation
      should be screened for in cases of nonsyndromic, familial sensorineural hearing
      loss compatible with maternal transmission. OBJECTIVES: To clarify the
      audiovestibular phenotype characteristics associated with a T7511C mutation in
      mitochondrial DNA and determine whether it causes isolated sensorineural hearing
      loss unaccompanied by other neuromuscular symptoms or signs. SUBJECTS AND
      METHODS: A proband and affected members of a Japanese family harboring a T7511C
      mutation in the mitochondrial tRNA(Ser(UCN)) gene were enrolled. Mutation
      analysis was done on genomic DNA extracted from blood samples. Auditory pathways
      involved were investigated in examinations that included pure-tone audiograms,
      acoustic reflexes, speech discrimination testing, distortion-product otoacoustic
      emissions, and auditory brainstem responses. The presence of other signs and
      symptoms, including vestibular ones, was investigated. RESULTS: We identified a
      homoplasmic T7511C mutation in the mitochondrial tRNA(Ser(UCN)) gene in this
      family. No other pathogenic mutations associated with hearing loss or common
      mitochondrial diseases were found. Hearing loss of cochlear origin mainly
      developed at mid to high frequencies. Vestibular systems were well preserved. No
      symptoms or signs characteristic of mitochondrial diseases were present in any
      family members.

PMID- 18340556
TI  - Cochlear neuronal tracing for frequency mapping with DiI, NeuroVue, and Golgi
      methods.
AB  - CONCLUSIONS: Labeling experiments using NeuroVue Red dye allowed us to
      demonstrate individual afferent fiber tracks in the cochlea from the synaptic
      region of the inner hair cell in the organ of Corti (OC) to the spiral ganglion
      in Rosenthal's canal. Further optimization is necessary to obtain 3-dimensional
      (3D) neural distribution in the apical region for frequency mapping. OBJECTIVES:
      We intend to develop a method by which the radial fibers of the spiral ganglion
      (SG) can be individually visualized and tracked in 3D from the base to the apex
      of the cochlea. The combined trajectories of fibers from each cochlea could then
      be calculated for modeling of the 3D relationship of OC and SG in cochlear
      implant studies to assist in the optimization of cochlear implants for music and
      speech perception in noise. MATERIALS AND METHODS: We tested three different
      methods to visualize cochlear nerve fibers from OC to SG. Adult rat and mouse
      ears were stained with DiI dye, modified Golgi-Cox method or NeuroVue dye,
      sectioned or whole-mounted, and viewed with confocal or standard light
      microscope. RESULTS: In DiI staining, spacial resolution and the number of
      neurons to be stained are too low to utilize this method to create a
      characteristic frequency map of the cochlea. The Golgi method mainly stained
      efferent nerve fibers, resulting in less information on cochlear nerve
      distribution. NeuroVue Red dye allowed clear tracking of individual fibers when
      combined with DAPI counterstaining.

PMID- 18340557
TI  - Questionnaire and interview in screening for hearing impairment in adults.
AB  - CONCLUSION: Questionnaire and brief interview played an important complementary
      role in the mass hearing screening. OBJECTIVES: To evaluate the efficacy of mass
      screening for hearing loss. SUBJECTS AND METHODS: Review of a 9-year prospective
      screening (n=31 902) in a university. The screening comprised pure tone hearing
      screening at two frequencies (1000 Hz and 4000 Hz) and a questionnaire. Brief
      interview was introduced during the later 4-year period. The final diagnosis was
      made in the university hospital. RESULTS: In hearing screening tests, approximate
      sensitivity was 89% for 1000 Hz and 91% for 4000 Hz. Approximate specificity was
      89% and 88% for 1000 Hz and 4000 Hz, respectively. Brief interview with the
      subjects on the spot improved the accuracy, especially in specificity. Low tone
      sensorineural hearing loss, exudative otitis media and chronic otitis media could
      be overlooked without questionnaires.

PMID- 18340558
TI  - Acute sensorineural hearing loss associated with aortitis syndrome.
AB  - CONCLUSIONS: Steroid treatment was effective in improving hearing in most
      episodes in our and previously reported patients with acute hearing loss
      associated with aortitis syndrome. This suggests that inflammatory changes due to
      autoimmune responses may play an important role in the manifestation of hearing
      loss in aortitis syndrome. OBJECTIVES: To clarify clinical features in patients
      with aortitis syndrome who exhibited hearing loss. CASE REPORTS: We describe two
      patients, 39-year-old and 53-year old women, who developed several episodes of
      acute sensorineural hearing loss associated with aortitis syndrome. RESULTS: In
      both patients, hearing loss involved the cochlea and hearing recovered following
      corticosteroid treatment. A literature review revealed that hearing loss was
      commonly manifested in middle-aged females and involved bilateral ears.
      Corticosteroid treatment was effective in improving hearing in most episodes in
      the previously reported cases as in our patients.

PMID- 18340559
TI  - The effect of eye position on the orientation of sound lateralization.
AB  - CONCLUSIONS: The data suggest that sound lateralization sensitivity during
      interaural time difference (ITD) discrimination is altered by eccentric gaze and
      that sound lateralization shifts toward the direction of the gaze. OBJECTIVE:
      Using dichotic sounds, the effect of eye position on the orientation of sound
      lateralization was investigated in humans. SUBJECTS AND METHODS: The subjects
      were studied by testing ITD discrimination under different conditions of visual
      fixation. RESULTS: The amplitudes obtained during the ITD discrimination tests
      during eccentric fixation were significantly greater than those obtained while
      gazing straight ahead (p<0.05). The median line of amplitude obtained during the
      ITD discrimination test shifted toward the direction of the gaze.

PMID- 18340560
TI  - Neurological complications after acoustic neurinoma radiosurgery: revised risk
      factors based on long-term follow-up.
AB  - CONCLUSIONS: The precise risk factors for neurological complications after
      acoustic neurinoma radiosurgery were identified on long-term follow-up. Type 2
      neurofibromatosis was found to be a risk factor for hearing loss and peripheral
      tumor dose was a risk factor for seventh and fifth cranial nerve injuries. These
      risk factors corresponded to those reported at other institutions. At the present
      time, controversy exists regarding history of prior surgical resection and tumor
      size as risk factors for cranial nerve complications. OBJECTIVES: To identify
      more precisely the risk factors for neurological complications after stereotactic
      radiosurgery (SRS) based on long-term follow-up. PATIENTS AND METHODS: Between
      June 1990 and September 1998, 138 patients with acoustic neurinomas had SRS at
      Tokyo University Hospital. Of these, the 125 patients who were followed up for at
      least 6 months were entered into the present study. The patients' ages ranged
      from 13 to 77 years (median 53 years). The average tumor diameter ranged from 6.7
      to 25.4 mm (mean 13.9 mm). The maximum tumor doses ranged from 20 to 40 Gy (mean
      29.8 Gy), and the peripheral doses ranged from 12 to 25 Gy (mean 15.4 Gy). One to
      12 isocenters were used (median 4). The follow-up period ranged from 6 to 191
      months (median 60 months). The potential risk factors for neurological
      complications were analyzed using two univariate actuarial analyses. The
      neurological complications studied included hearing loss, facial palsy, and
      trigeminal nerve dysfunction. The variables analyzed were age, gender, prior
      operation, neurofibromatosis type 2 (NF2), tumor diameter, maximum tumor dose,
      peripheral tumor irradiation dose, and the number of isocenters. Variables with
      significant p values (<0.05) on both actuarial analyses were considered risk
      factors. RESULTS: NF2 was significantly correlated with both total hearing loss
      and pure tone threshold (PTA) elevation; a history of prior surgical resection,
      tumor size, and the peripheral tumor dose were significantly correlated with
      facial palsy; and the peripheral tumor dose was significantly correlated with
      trigeminal neuropathy.

PMID- 18340561
TI  - Prediction of metabolic clearance using fresh human hepatocytes: comparison with
      cryopreserved hepatocytes and hepatic microsomes for five benzodiazepines.
AB  - 1. Predictions of in vivo intrinsic clearance from cryopreserved human
      hepatocytes may be systematically low. In the current study, the metabolite
      kinetics of a series of CYP3A4 substrates (benzodiazepines) in fresh human
      hepatocytes from five donors, via a major UK supplier, were investigated and
      compared with those previously reported (by the authors' laboratory) for
      cryopreserved human hepatocytes and hepatic microsomes. 2. A high incidence of
      autoactivation (up to tenfold) and heteroactivation (by testosterone, up to 14
      fold) among the major pathways was observed. CYP capacity (V(max)) was marginally
      lower and 'affinity' constants (K(M), S(50)) were marginally greater compared
      with cryopreserved hepatocytes. 3. Average intrinsic clearance (based on maximal
      clearance, CL(max)) was sevenfold lower than in cryopreserved hepatocytes
      (reflecting sensitivity of intrinsic clearance estimation in vitro to mechanistic
      parameter values, particularly those involving atypical kinetics), but scaled
      intrinsic clearances for fresh (and cryopreserved) hepatocytes were within the
      range previously determined in hepatic microsomes. 4. There was no evidence from
      this series of studies that fresh hepatocytes provide quantitatively improved
      estimates of intrinsic clearance over cryopreserved hepatocytes.

PMID- 18340562
TI  - In vivo approach for the evaluation of mechanism-based inhibition of cytochrome
      P450 3A in rats.
AB  - 1. There have been no reports showing that the area under the concentration-time
      curve (AUC) of a probe drug is elevated due to mechanism-based inhibition (MBI)
      of drug-metabolizing enzymes in animals. This study ascertained that mechanism
      based inhibitors reported to induce drug-drug interactions (DDIs) in humans also
      caused MBI in rats. 2. Midazolam (MDZ), mainly metabolized by cytochrome P450 3A
      in rats, and mibefradil, which showed the most intense time-dependent inhibition
      among the inhibitors tested, were selected as the probe and the inhibitor,
      respectively. Following pretreatment of mibefradil at 24 h before MDZ
      administration in rats, the C(max) and AUC values of MDZ were significantly
      elevated in comparison with the control. The free plasma concentration of
      mibefradil was substantially lower than the IC(50) value observed in the in vitro
      inhibition study, suggesting that the DDI was due to MBI. 3. It is concluded that
      the evaluation of MBI in rats in vivo in combination with in vitro data using
      human enzymes could be useful to evaluate risk in clinical studies.

PMID- 18340563
TI  - Pharmacokinetic characterization of hydroxylpropyl-beta-cyclodextrin-included
      complex of cryptotanshinone, an investigational cardiovascular drug purified from
      Danshen (Salvia miltiorrhiza).
AB  - 1. The study aimed to investigate the pharmacokinetics of cryptotanshinone in a
      hydroxylpropyl-beta-cyclodextrin-included complex in dogs and rats. 2. Animals
      were administrated the inclusion complex of cryptotanshinone and the
      concentrations of cryptotanshinone and its major metabolite tanshinone IIA were
      determined by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
      3. Cryptotanshinone in inclusion complex was absorbed slowly after an oral dose,
      and the C(max) and AUC(0-)(t) were dose-proportional. The bioavailability of
      cryptotanshinone in rats was (6.9% +/- 1.9%) at 60 mg kg(-1) and (11.1% +/- 1.8%)
      in dogs at 53.4 mg kg(-1). The t(1/2) of the compound in rats and dogs was 5.3
      7.4 and 6.0-10.0 h, respectively. Cryptotanshinone showed a high accumulation in
      the intestine, lung and liver after oral administration, while the lung, liver
      and heart had the highest level following intravenous dose. Excretion data in
      rats showed that cryptotanshinone and its metabolites were mainly eliminated from
      faeces and bile, and the dose recovery rate was 0.02, 2.2, and 14.9% in urine,
      bile, and faeces, respectively. 4. The disposition of cryptotanshinone in an
      inclusion complex was dose-independent and the bioavailability was increased
      compared with that without cyclodextrin used to formulate the drug.
      Cryptotanshinone was distributed extensively into different organs. Excretion of
      cryptotanshinone and its metabolites into urine was extremely low, and they were
      mainly excreted into faeces and bile.

PMID- 18340564
TI  - Disposition and metabolism of the colchicine derivative [14C]-ZD6126 in rat and
      dog.
AB  - 1. The tissue distribution, disposition and metabolism of ZD6126, a novel
      vascular targeting agent, were investigated in rat and dog. This paper comprises
      the findings of several investigations, including rat quantitative whole-body
      autoradiography (QWBA), rat and dog balance and metabolism (both in intact and
      bile-duct-cannulated animals), rat enterohepatic recirculation, and comparison of
      metabolism between young and mature rats. 2. Following intravenous administration
      of [(14)C]-ZD6126 to rats, quantitative whole-body autoradiography showed that
      radioactivity was widely distributed, then rapidly eliminated from the body. 3.
      ZD6126-related material was eliminated primarily in the faeces (approximately
      86%) of both species, indicating the importance of biliary clearance. 4.
      Metabolite profiles from intact and bile-duct-cannulated animals suggest that
      ZD6126 is cleared primarily by metabolism. In rat, the major metabolites were
      ZD6126 phenol, its glucuronide and other metabolites consistent with O
      demethylation and conjugation. ZD6126 was more extensively metabolized by male
      than female rats, and also in young compared with mature rats. In dog, metabolism
      occurred primarily via direct glucuronidation of the active species, ZD6126
      phenol. 5. Following intraduodenal infusion of bile containing [(14)C]-ZD6126
      related material to bile-duct-cannulated rats, 30% of the radioactivity was
      subsequently recovered in bile and urine, showing that one or more components in
      bile are reabsorbed and undergo enterohepatic recirculation.

PMID- 18340565
TI  - Dietary salt does not influence the disposition of verapamil enantiomers in
      relation to efflux transporter ABCB1 genetic polymorphism in healthy Korean
      subjects.
AB  - To evaluate the effects of dietary salt on the stereoselective disposition of
      verapamil enantiomers in relation to the transporter ABCB1 2677GG/3435CC and
      2677TT/3435TT haplotypes, ten healthy subjects were asked to take diets of three
      different salt levels for 7 days in a randomized, three-way crossover manner. The
      plasma concentrations of verapamil and norverapamil enantiomers were determined
      after a single oral dose of 240 mg verapamil on the last day of each phase.
      Pharmacokinetic parameters were calculated by non-compartmental analysis
      techniques and compared among the three different dietary salt phases. Compared
      with the medium salt diet, the high and low salt diets had no significant effect
      on the disposition of verapamil enantiomers. Moreover, the ABCB1 haplotypes did
      not alter the impact of dietary salt, although ABCB1 2677TT/3435TT subjects had
      slightly, but not significantly, higher C(max) and area under the curve (AUC) and
      lower T(max) for the verapamil enantiomers than did 2677GG/3435CC subjects in
      each salt phase.

PMID- 18340566
TI  - Effect of gender, dose, and time on 3-(3,5-dichlorophenyl)-2,4-thiazolidinedione
      (DCPT)-induced hepatotoxicity in Fischer 344 rats.
AB  - 1. The thiazolidinedione ring present in drugs available for type II diabetes can
      contribute to hepatic injury. Another thiazolidinedione ring-containing compound,
      3-(3,5-dichlorophenyl)-2,4-thiazoli-dinedione (DCPT), produces liver damage in
      rats. Accordingly, the effects of gender, dose, and time on DCPT hepatotoxicity
      were therefore evaluated. 2. Male rats were more sensitive to DCPT (0.4-1.0 mmol
      kg(-1) by intraperitoneal administration) as shown by increased serum alanine
      aminotransferase levels and altered hepatic morphology 24 h post-dosing. Effects
      in both genders were dose dependent. In males, DCPT (0.6 mmol kg(-1)) produced
      elevations in alanine aminotransferases and changes in liver sections 3 h after
      dosing that progressively worsened up to 12 h. DCPT-induced renal effects were
      mild. 3. It is concluded that male rats are more susceptible to DCPT
      hepatotoxicity and that damage occurs rapidly. DCPT primarily affects the liver
      and can be a useful compound to investigate the role of the thiazolidinedione
      ring in hepatic injury. However, the gender dependency and rapid onset of DCPT
      hepatotoxicity require further investigation.

PMID- 18340568
TI  - Preface. To commemorate the retirement of Professor Kimitaka Kaga from the
      Graduate School of Medicine, University of Tokyo.

PMID- 18340569
TI  - Development and regeneration of hair cells.
AB  - The vertebrate inner ear is derived from the otic placode and undergoes a
      complicated series of morphogenetic processes to differentiate into an elaborate
      structure harboring mechanosensory epithelia featuring hair cells, the
      mechanoreceptors of hearing and balance. Recently, the principal mechanisms
      producing hair cells and the key molecules involved in their fate determination
      and differentiation have been gradually unveiled. The in-depth understanding of
      hair cell development is consequently providing clues to strategies for mammalian
      hair cell regeneration. Among them, the identification and characterization of
      progenitor cells for the hair cell lineage, which is just emerging, is of
      particular interest. Herein, we review the molecular mechanisms of inner ear
      development with particular focus on perspectives for hair cell regeneration.

PMID- 18340570
TI  - Migraine-associated vertigo: clinical characteristics of Japanese patients and
      effect of lomerizine, a calcium channel antagonist.
AB  - CONCLUSION: Lomerizine, a calcium channel blocker, may be effective as a
      treatment for migraine-associated vertigo (MAV). Objective. To determine the
      clinical characteristics of patients with MAV in Japan and the effectiveness of
      lomerizine. PATIENTS AND METHODS: This was a retrospective chart review carried
      out in a university hospital of 33 patients who fulfilled the diagnostic criteria
      for MAV. All patients were initially treated with dietary manipulation. If this
      therapy was unsuccessful, oral medications, mainly lomerizine, were administered.
      Medical records were reviewed to find clinical characteristics of patients with
      MAV and to evaluate the effects of the therapy on vertigo/dizziness symptoms.
      RESULTS: A marked female predominance was found (23 women, 10 men). The frequency
      and the duration of vertigo varied across patients. About 60% of the patients had
      cochlear symptoms during an attack, among which bilateral aural fullness was most
      frequent. Oto-neurological examination showed abnormalities in 33% of the
      patients. Overall, 27 of the 33 patients (82%) responded to our therapy. Among
      the 22 patients who were prescribed lomerizine, 19 patients (87%) showed
      resolution or significant improvement of the symptoms.

PMID- 18340571
TI  - Aplasia and displacement of the horizontal portion of the petrous carotid artery
      in mandibulofacial dysostosis.
AB  - CONCLUSIONS: The horizontal portion of the petrous carotid artery (HPCA) of
      mandibulofacial dysostosis (MFD) patients had anterior-inferior displacement or
      was aplasia at birth. Our findings indicate that most MFD patients have aplasia
      of the internal carotid artery. This information may be very important for safe
      reconstruction surgery in atresia. OBJECTIVE: MFD rarely has malformations of the
      cardiovascular system such as those seen in Goldenhar syndrome. This study aimed
      to compare MFD patients and normal subjects with respect to the length and
      diameter of the HPCA. SUBJECTS AND METHODS: We radiographically studied 22 MFD
      patients (44 sides) using high-resolution computed tomography (HRCT), measuring
      the length and diameter of the HPCA and the angle between the right and left HPCA
      using computer software. Findings were compared with those in 86 ears with normal
      auricles (control group) using the nonparametric test. RESULTS: The HPCA in MFD
      patients averaged 23.2 mm in length and 4.8 mm in diameter. The angle between the
      right and left HPCA averaged 100.2 degrees. In MFD patients, on average, HPCA
      were 2.0 mm shorter (p=0.001) and 0.4 mm narrower (p=0.016) than in control
      subjects. Mean angle between right and left HPCA was 5.4 degrees more acute in
      MFD patients than in control subjects (p=0.026). Moreover, the genu of the
      vertical and horizontal petrous ICA in the MFD group was on average 3.2 mm more
      inferior than in controls (p<0.001).

PMID- 18340572
TI  - Neuro-otological findings in patients with very small (border zone) cerebellar
      infarcts.
AB  - CONCLUSIONS: The symptoms and signs in patients with very small (border zone)
      cerebellar infarcts (VSCIs) may mimic those in benign peripheral vestibular
      disorders, except that smooth pursuit eye movement is disturbed in patients with
      VSCI. OBJECTIVES: VSCIs are located at the boundary territories between well
      defined cerebellar arteries and are frequently manifested by dizziness or
      vertigo. The aim of the current study was to clarify the clinical characteristics
      of vestibular symptoms and signs associated with VSCI. PATIENTS AND METHODS: We
      studied the neuro-otological findings in five vertiginous patients, who were
      diagnosed as having VSCI based on magnetic resonance imaging (MRI). RESULTS: Four
      patients complained of only dizziness or only vertigo, and one complained of
      dizziness with dysarthria. Horizontal spontaneous nystagmus and saccadic eye
      movement on eye tracking test were observed in all patients, but there were no
      abnormalities on examinations for saccade, optokinetic pattern, or visual
      suppression. Canal paresis was present in three patients.

PMID- 18340573
TI  - Does acute dysfunction of the saccular afferents affect the subjective visual
      horizontal in patients with vestibular neurolabyrinthitis?
AB  - CONCLUSIONS: The results of a series of studies including the present study
      suggest that acute dysfunction of the utricular afferents accompanied by acute
      dysfunction of the saccular afferents might require more time for the
      compensation of the otolith-ocular system than acute utricular dysfunction that
      was not accompanied by acute saccular dysfunction. Perhaps the inputs from the
      saccule also have some contribution to the subjective visual horizontal (SVH).
      OBJECTIVE: To clarify if acute dysfunction of the saccular afferents affects the
      SVH. PATIENTS AND METHODS: Twenty-six patients with vestibular neurolabyrinthitis
      (20 men and 6 women, 23-67 years of age) were enrolled in this study. They had
      undergone measurement of SVH at the early stage (within 1 month after the attack)
      and 3 months after the attack. For the measurement of SVH, we used a device that
      has a red bar of light-emitting diodes with a head fixing frame. They also
      underwent vestibular evoked myogenic potentials (VEMPs) testing. For the
      recording of VEMPs, 95 dBnHL clicks were presented. RESULTS: Patients with
      vestibular neurolabyrinthitis showed deviation of SVH toward the affected side
      down at the early stage after the attack, irrespective of VEMP results. However,
      3 months after the attack SVH was significantly more deviated toward the affected
      side-down in patients who showed absent VEMPs than those with VEMPs present
      (p<0.01 Mann-Whitney U test).

PMID- 18340574
TI  - Benign mass lesions deep inside the temporal bone: imaging diagnosis for proper
      management.
AB  - CONCLUSION: Among mass lesions inside the temporal bone, benign tumors and
      cholesteatomas can be differentiated by contrast enhancement in T1-weighted
      images (T1WI) and by diffusion-weighted images (DWI). Moreover, DWI will also
      facilitate discrimination between cholesteatomas accompanied by granulation and
      other non-neoplastic lesions such as mucoceles and cholesterol granulomas.
      OBJECTIVES: To review the imaging characteristics of mass lesions inside the
      temporal bone and to investigate pertinent imaging modalities for differential
      diagnosis, which is crucial for appropriate treatment planning. PATIENTS AND
      METHODS: This was a retrospective case series study of six patients seen between
      2002 and 2005 with mass lesions deep inside the temporal bone. RESULTS: One
      patient had facial schwannoma, two had glomus jugulare tumor, and three had
      cholesteatoma. Plain high resolution CT gave few clues to the nature of the mass
      lesions. MRI study provided us with better clues: contrast enhancement on T1WI
      was observed only in benign tumors and only cholesteatomas showed high intensity
      on DWI. With the assistance of neurosurgeons, surgery was successfully performed
      in all cases.

PMID- 18340575
TI  - Eye movement disorders in myotonic dystrophy type 1.
AB  - CONCLUSIONS: No definite sign was found of central oculomotor system disorders
      being independent of saccadic slowing because (1) diminished maximum slow phase
      velocity of the optokinetic nystagmus (OKNspv) was closely related to saccadic
      slowing (p<0.01, r=0.59), (2) maximum frequency of optokinetic nystagmus (OKNfq)
      was normal, (3) visual suppression (VS) change was mild, and (4) the diminished
      maximum slow phase velocity of the caloric nystagmus (CNspv) seen in some
      patients is explained by both peripheral and central vestibular involvement.
      These findings support the extraocular muscle hypothesis. OBJECTIVE: To assess
      whether eye movement disorders seen in patients with myotonic dystrophy type 1
      (DM1) are caused by central oculomotor system involvement or extraocular muscle
      damage. PATIENTS AND METHODS: Oculomotor functions and their correlation with
      (CTG)n length were studied in 29 DM1 patients and 12 age-matched controls.
      RESULTS: Values for saccadic velocity (p<0.005), maximum OKNspv (p<0.005), and
      maximum CNspv (p<0.01) in the patient group were markedly lower than in the
      control group. VS of caloric nystagmus in the patient group was slightly lower
      than that in the controls. No significant difference was found between the two
      groups in the maximum OKNfq. Patients with greater (CTG)n lengths had lower
      saccadic velocities (p<0.01, r=0.71).

PMID- 18340576
TI  - + - Reconstruction of the intratemporal facial nerve using interposition nerve
      graft: time course of recovery in facial movement and electrophysiological
      findings.
AB  - CONCLUSIONS: Data about the recovery course of facial function after
      intratemporal facial nerve reconstruction using interposition nerve graft would
      provide useful information for clinicians to understand the regenerative process
      of the facial nerve after this type of surgery. It would also enable them to
      obtain informed consent from the patients by preoperatively explaining the
      predicted outcome of the postoperative facial paralysis. OBJECTIVE: The purpose
      of this study was to describe the recovery course of facial movement and
      electrophysiological findings after intratemporal facial nerve reconstruction
      using interposition graft. PATIENTS AND METHODS: Five patients who underwent
      reconstruction of the facial nerve using interposition nerve graft immediately
      after facial nerve excision during surgery for temporal bone lesions were
      included in this study. Each patient was evaluated for facial movement
      (Yanagihara score), blink reflex (BR), and electroneurography (ENoG)
      preoperatively and postoperatively. RESULTS: Improvement in facial movement began
      8-10 months postoperatively. The score then gradually increased, and reached a
      plateau level by 2 years following surgery. The final score in four of the five
      patients ranged from 20 to 24 points, while the facial score of one patient only
      reached 12 points even at 3 years after surgery. All patients demonstrated
      moderate to severe synkinesis. The reappearance of R1 in BR occurred 7-10 months
      postoperatively, almost simultaneously with the beginning of recovery of facial
      movement. The latency of R1 on the operated side became shortened with increasing
      postoperative time, although it remained considerably longer than that on the
      unoperated side, even after 2 postoperative years. The onset of recovery of ENoG
      value (10-12 months postoperatively) was always delayed compared with the actual
      facial movement recovery and never returned to the level in the unoperated side.

PMID- 18340577
TI  - Peritonsillar abscess with parapharyngeal and retropharyngeal involvement:
      incidence and intraoral approach.
AB  - CONCLUSION: This study illustrates common sites of infection seen in
      peritonsillar abscesses with involvement of the pharyngeal space and
      retropharyngeal space. Abscesses behind and/or inferior to the tonsil were
      encountered more frequently than expected. In these cases, the drainage had to be
      placed in the inferior pole of the tonsil and these types were frequently seen in
      older patients. OBJECTIVES: The aim of this study was to assess to what extent
      abscesses spread in patients with peritonsillar abscess and to determine to what
      extent pus can be drained intraorally. PATIENTS AND METHODS: The clinical charts
      of 45 patients with peritonsillar abscess involvement of the parapharyngeal space
      and/or retropharyngeal space were retrospectively reviewed. RESULTS: In 45 cases,
      21 patients were diagnosed with the superior type, and we could drain the pus
      intraorally in 90% of the patients. On the other hand, 24 cases were diagnosed
      with the inferior type and they were drained intraorally in 58% of the cases.

PMID- 18340578
TI  - Clinical usefulness of endoscopic intranasal dacryocystorhinostomy.
AB  - CONCLUSIONS: Endoscopic intranasal dacryocystorhinostomy (DCR) has the following
      advantages over external surgery: pain and hemorrhage are minimal; postoperative
      facial swelling and scarring are absent; and symptoms resolve rapidly after
      surgery. Furthermore, as no significant differences in postoperative results were
      apparent between external and endoscopic intranasal DCR, and because no facial
      skin incision is required, the clinical usefulness of endoscopic intranasal DCR
      is high. OBJECTIVES: In the treatment of nasolacrimal duct obstruction or chronic
      dacryocystitis in which epiphora or ocular discharge are chief complaints,
      endoscopic intranasal DCR is a safe, easy, minimally invasive, and reliable
      approach. In the present study, we describe the surgical procedures, techniques,
      and results of endoscopic intranasal DCR, and investigate its clinical
      usefulness. SUBJECTS AND METHODS: The subjects were 21 patients with nasolacrimal
      duct obstruction who underwent a total of 24 endoscopic intranasal DCR
      procedures. Etiologies of the obstruction were, respectively, cryptogenic
      (62.5%), secondary to partial maxillectomy (16.7%), complication of sinus surgery
      (12.5%), and due to underlying disease--Wegener's granulomatosis (4.2%) or nasal
      T-cell lymphoma (4.2%). To assess the clinical usefulness of this procedure,
      postoperative courses were assessed by reviewing medical records and conducting
      telephone interviews. In addition, to assess the therapeutic effects,
      postoperative results were statistically compared to those of external DCR.
      RESULTS: Closure of the surgical opening was seen in two cases (8.3%). In both
      cases, after the closed region was opened using an endoscopic procedure, symptoms
      resolved. Finally, lacrimal passage obstruction was not observed by lacrimal
      irrigation in any patient. None of the patients in the present study experienced
      major complications during or after surgery, and since their symptoms improved,
      the degree of satisfaction was high. When compared to external DCR, endoscopic
      intranasal DCR showed no statistically significant difference in postoperative
      results, thus confirming that similar therapeutic effects could be obtained for
      the two procedures.

PMID- 18340579
TI  - Immunohistochemical study of m1-m5 muscarinic receptors and nNOS in human
      inferior turbinate mucosa.
AB  - CONCLUSION: This study suggested that nitric oxide (NO) takes part in the
      parasympathetic nerve control functions mainly through m3 receptors and
      subsequently through m1 receptors. OBJECTIVES: The regulation of glandular
      secretions and vasomotor tone in human nasal mucosa implicates muscarinic
      receptors. There are five recognized classes (m1-m5) of muscarinic receptor
      subtypes. NO is a free radical gas that has been found to be produced in neuronal
      cells by the action of enzyme neural nitric oxide synthase (nNOS). The aim of
      this study was to identify the colocalization of muscarinic receptor subtypes (m1
      m5) and nNOS in the human inferior turbinate mucosa. MATERIALS AND METHODS: Human
      inferior turbinate mucosa was stained by using the antibody of muscarine receptor
      subtypes and nNOS in an immunohistochemical double-staining method. RESULTS: The
      colocalization of m3 receptors and nNOS-immunoreactive nerve fibers was most
      extensively distributed on glands, vessels, and epithelium in all muscarinic
      receptor subtypes. These findings lead us to propose that NO also acts as a
      neurotransmitter in glands, vessels, and epithelium of the human nasal mucosa and
      can be assigned to parasympathetic nerve structures through m3 receptors mainly
      and m1 receptors subsequently.

PMID- 18340580
TI  - Age-related change in the axonal diameter of the olfactory nerve in mouse lamina
      propria.
AB  - CONCLUSION: The present study demonstrated the age-related decrease in the axonal
      diameter of the olfactory nerve. This finding may represent the maturational
      change of the olfactory receptor neurons. OBJECTIVES: The aim of this study was
      to investigate age-related changes in the axonal diameter of the olfactory nerve
      in the lamina propria. MATERIALS AND METHODS: Female ICR mice, postnatal age 10
      days, 3 months, 7 months, and 16 months, were studied. The electron micrographs
      of septal olfactory mucosa were used to measure the axonal diameters of olfactory
      nerves. RESULTS: The distribution of the diameter shifted toward the thinner side
      between 10-day-old and 3-month-old mice. The axonal diameter showed significant
      decreases (p < 0.001) from the age of 10 days to that of 3 months.

PMID- 18340581
TI  - Olfactory neuroblastoma: long-term clinical outcome at a single institute between
      1979 and 2003.
AB  - CONCLUSIONS: The progression of olfactory neuroblastoma showed a biphasic
      pattern. As well as Hyams' histopathological grading and neck metastasis at
      presentation, early phase recurrence should be regarded as an important
      prognosticator. A high local failure rate suggests that craniofacial resection
      followed by postoperative radiotherapy should still be the standard treatment for
      olfactory neuroblastoma. OBJECTIVE: The aim of this study was to evaluate factors
      associated with survival and local control of olfactory neuroblastoma in the long
      run and to estimate treatment strategies. PATIENTS AND METHODS: Twelve patients
      (seven men and five women) who had undergone initial curative treatment for
      olfactory neuroblastoma were retrospectively analyzed. RESULTS: Cause-specific 10
      year survival was 64.8%, while disease-free 10-year survival remained 28.6%.
      Local failure was found in half of the patients. All of the three patients who
      did not receive radiotherapy developed local failure. A biphasic pattern of
      recurrence was observed. The early phase recurrence group showed a significantly
      poorer survival than the late phase recurrence group. Hyams' histopathological
      grading and neck metastasis at presentation were also correlated with survival.

PMID- 18340582
TI  - A clinical study of post-cricoid carcinoma.
AB  - CONCLUSION: The local control rate following surgery was very high in patients
      with post-cricoid carcinoma; however, many of the patients undergoing surgery
      later developed distant metastasis. Therefore, establishment of chemotherapeutic
      regimens for preventing distant metastasis is desirable. OBJECTIVES: To define
      the clinical course of the cancer, the problems that might be associated with its
      treatment, and the future course of treatment of this cancer at our hospital.
      PATIENTS AND METHODS: This study included 21 patients with post-cricoid carcinoma
      who had undergone primary treatment at our hospital between 1989 and 2004. The
      present study was designed to retrospectively investigate the therapeutic outcome
      of post-cricoid carcinoma at our hospital. RESULTS: The 5-year cause-specific
      survival rate was 52%. All the patients who eventually died did so within 3 years
      of the treatment. Seven patients had distant metastases, representing a higher
      frequency as compared with that of patients with recurrence of the primary focus
      and cervical lymph node metastasis. All of these patients who had been treated by
      surgery died of the cancer.

PMID- 18340583
TI  - Treatment results for 84 patients with base of tongue cancer.
AB  - CONCLUSIONS: For T2 tumors, surgery was indicated if functional preservation was
      possible. For T3/T4 tumors, the rate of primary disease control was not high and
      surgery frequently involved total laryngectomy. Points that surgeons must heed
      when performing such surgery were delineated. OBJECTIVES: Because tumors
      originating from the base of the tongue are rare, few large-scale studies of such
      tumors have been performed. We reviewed treatments and outcomes at our department
      to establish effective future therapeutic plans. PATIENTS AND METHODS: From 1971
      to 2000, 84 patients with previously untreated and resectable squamous cell
      carcinoma of the base of the tongue were treated at the Head and Neck Department
      of the Cancer Institute Hospital, Tokyo. Treatment selection and results were
      investigated. RESULTS: The main treatment options were radiotherapy for primary
      lesions < or = T2 and surgery for primary lesions > or = T3. Overall disease
      specific 5-year cumulative survival rate was 59.8%, but there was no significant
      difference in survival rate at each stage between the two treatments. Among
      patients who died of the primary disease, the area that was most difficult to
      control was the superior margin of the lateral wall of the oropharynx (n=7). The
      incidence of contralateral or retropharyngeal lymph node metastasis was low if
      tumors neither crossed the midline nor infiltrated the lateral wall. While total
      laryngectomy was performed on 48 patients, the larynx was operatively preserved
      in 5 T3 patients and one T4 patient.

PMID- 18340584
TI  - Clinicopathological factors related to cervical lymph node metastasis in a
      patient with carcinoma of the oral floor.
AB  - CONCLUSION: Tumors developing into the muscle layer and tumor thickness > or =5
      mm are the most important risk factors associated with nodal metastasis.
      OBJECTIVE: It is necessary to identify the risk factors associated with cervical
      metastasis in patients with oral floor cancer to reveal the role of elective neck
      dissection for oral floor cancer. PATIENTS AND METHODS: Forty-eight patients with
      oral floor cancer were retrospectively analyzed for a correlation between
      clinicopathologic factors and cervical lymph node metastasis using Fisher's exact
      test and a logistic regression test. RESULTS: Univariate analysis showed
      significantly positive correlations for growth type, mitosis, perineural
      invasion, vascular invasion, lymphatic invasion, depth, thickness, and
      infiltration growth ratio. Multivariate analysis had a significantly positive
      correlation with nest formation and depth in all patients, and with thickness in
      patients with T1 or T2. In patients with bilateral cervical lymph node
      metastasis, lymph node metastasis was significantly positively correlated with
      perineural invasion.

PMID- 18340585
TI  - Prognostic factors for hypopharyngeal cancer: a univariate and multivariate study
      of 142 cases.
AB  - CONCLUSIONS: Reduction of distant metastases is essential for better survival.
      Effective adjuvant chemotherapy should be developed for patients with advanced
      primary disease (T>2) as well as for patients with advanced nodal status (N>0 or
      PLN>2). OBJECTIVES: The aim of this study was to identify prognostic factors for
      hypopharyngeal cancer. PATIENTS AND METHODS: In all, 142 previously untreated
      patients were analyzed retrospectively; 75% of the cases were stage III or IV.
      Surgical resection was administered as primary treatment to 116 of the patients
      (82%), while 26 patients (18%) underwent primary radiotherapy. RESULTS: The cause
      specific 5-year actuarial survival was 46.3%. Distant metastases were the most
      frequent (23%) cause of failure, followed by local recurrence (15%), and regional
      recurrence (13%). Cox's regression analysis showed that the significant factors
      affecting cause-specific survival were N classification, T classification, number
      of pathological lymph node metastases (PLN), lymphatic invasion, and positive
      surgical margin. Similarly, T classification and PLN affected distant metastases.

PMID- 18340586
TI  - Carcinoid tumor of the larynx: clinical analysis of 33 cases in Japan.
AB  - CONCLUSION: In regard to the treatment of carcinoid tumor of the larynx,
      irradiation is not effective and tumor excision with a minimum surgical margin is
      associated with a high risk of local recurrence. Lymph node metastases to the
      neck are associated with worsening of the prognosis. To improve the survival
      rate, primary resection with a sufficient surgical margin (e.g. partial
      laryngectomy) and (elective) neck dissection is recommended, even for patients
      with early stage carcinoid tumors of the larynx. OBJECTIVE: The objective of this
      study was to clarify the prognostic factors, modalities of treatment for the
      primary lesions, and importance of neck dissection in the treatment of carcinoid
      tumors of the larynx. PATIENTS AND METHODS: The data of 33 cases of carcinoid of
      the larynx reported from Japan (including 2 of our cases) were analyzed. RESULTS:
      The distributions of the T and N classifications of the lesions were as follows
      T1, 50.0%; T2, 32.2%; T3, 14.3%; T4, 3.6%; N0, 57.1%; N1, 17.9%; N2, 25.0%; and
      N3, 0%. Fifteen patients underwent radiation therapy, of whom five underwent
      curative radiotherapy. While complete remission (CR) was maintained in one of
      these patients (T1N0), the remaining four patients developed recurrence. Five
      patients underwent preoperative radiation therapy. The response to the treatment
      was rated as no change in four patients and as progressive disease in the
      remaining one patient. Among the patients with N0 disease, seven patients (43.8%)
      developed lymph node metastases in the neck postoperatively. Distant metastases
      were the most frequent cause of death in the patients. The 3-year, 5-year, and 10
      year survival rates of the patients were 58.5%, 36.5%, and 12.2%, respectively.
      Significant differences were recognized in the survival rates between patients
      with and without neck lymph node involvement at the first treatment (p=0.008),
      and between patients with and without postoperative lymph node recurrence in the
      neck (p=0.037).

PMID- 18340587
TI  - A new aspect of tri-modal therapy with superselective intra-arterial chemotherapy
      in maxillary sinus carcinoma.
AB  - CONCLUSION: This superselective intra-arterial intervention technique enabled us
      to administer a higher dose of cisplatinum to the local lesion with a lower
      incidence of adverse issues by use of neutralizer, compared with the conventional
      methods. OBJECTIVE: A wide variety of modalities, including surgery,
      radiotherapy, and chemotherapy, alone or in combination, have been reported for
      the treatment of maxillary sinus cancer. However, there is still much controversy
      with regard to the optimum treatment to obtain better local control and
      acceptable preservation of shape and function. Since 2001, we have performed
      superselective intra-arterial infusion chemotherapy in combination with
      radiotherapy and surgery aiming at a higher local control rate. PATIENTS AND
      METHODS: This was a review of prospective collected data. The therapeutic design
      consisted of weekly intra-arterial infusion of high dose CDDP with concomitant
      radiotherapy and planned surgery performed during chemo-radiation therapy. From
      June 2001 to January 2004, 14 patients with squamous cell carcinoma of maxillary
      sinus underwent this treatment procedure at the University of Tokyo Hospital.
      RESULTS: The local response rate with this combined therapy was 85.7%. Overall
      survival rates at 1 and 2 years were 78.6% and 56.2%, respectively, with median
      follow-up of 25.5 months.

PMID- 18340588
TI  - Otosclerosis associated with Ehlers-Danlos syndrome: report of a case.
AB  - Hearing loss occurs rarely in Ehlers-Danlos syndrome (EDS). We report a case of a
      24-year-old woman with EDS who had conductive deafness due to otosclerosis and
      scar tissues around the malleus and incus. The scar was considered to develop by
      inflammatory response specific to EDS that had been induced by otitis media with
      effusion. Following stapes mobilization and removal of the scar tissues, her
      hearing was improved for several months but showed deterioration thereafter,
      probably due to recurrence of ossicular fixation. The tendency toward scar
      formation, infection, and inflammatory response, especially to foreign bodies, in
      EDS needs to be kept in mind to determine treatment of choice in patients with
      EDS and conductive hearing loss.

PMID- 18340589
TI  - Parathyroid adenoma causing spontaneous cervical hematoma: a case report.
AB  - A case of parathyroid adenoma causing a spontaneous cervical hematoma is
      reported. A 55-year-old woman presented with painful swallowing, dysphagia, and
      dyspnea. Primary hyperparathyroidism and a parathyroid tumor on the left side of
      the neck had been found 2 years earlier. Fiberoptic laryngoscopy and computed
      tomography (CT) showed a narrowing of the airway as a result of a retropharyngeal
      hematoma, and tracheostomy was carried out. Parathyroidectomy was performed 5
      months after the absorption of the hematoma, with no complications. A
      pathological diagnosis revealed a parathyroid adenoma with hemosiderin deposition
      and fibrosis. Serum calcium and intact parathormone levels normalized
      postoperatively. Although a spontaneous cervical hematoma resulting from
      parathyroid tumors rarely occurs, it may lead to an airway compromise. Physicians
      should be aware of this if such tumors are managed conservatively without
      surgery.

PMID- 18340590
TI  - Vocal cord abductor paralysis in multiple system atrophy: a case report.
AB  - Multiple system atrophy (MSA) is a progressive neurodegenerative disease that is
      characterized by varying degrees of parkinsonism and cerebellar, corticospinal,
      and autonomic dysfunction. Vocal cord abductor paralysis (VCAP) is considered a
      sign of a poor prognosis in MSA, because it is a life-threatening complication
      that may cause nocturnal sudden death. This case report presents a patient who
      was treated for Parkinson's disease, and complained of dizziness and sleep apnea.
      We examined VCAP using fiberoptic laryngoscopy as the possible cause of sleep
      apnea. VCAP usually occurs in the advanced stages of MSA and is accompanied by a
      worsening of other symptoms. Optokinetic nystagmus was severely impaired and the
      caloric test response was bilaterally absent. Objective findings such as VCAP and
      abnormal neuro-otological results led to the diagnosis of MSA.

PMID- 18340591
TI  - Bilateral hearing loss due to a meningioma located in the left posterior fossa: a
      case report.
AB  - We report the case of a 39-year-old woman with a left side meningioma, suffering
      from bilateral sensorineural hearing loss, who recovered audiometric hearing in
      both ears after surgery. A preoperative pure tone audiogram (PTA) revealed a
      bilateral sensorineural hearing loss. Several examinations for sensorineural
      hearing loss indicated cochlear and retrocochlear hearing loss in the left ear
      and cochlear hearing loss in the right ear. After the operation, bilateral
      hearing loss due to a left posterior fossa meningioma gradually improved. One
      year after surgery, with the exception of hearing at frequencies of 4 and 8 kHz
      in the left ear, the postoperative audiogram had improved to an almost normal
      level. We speculate that hearing loss in the left ear may have been induced by
      the indirect compression of the cochlear nerve caused by the tumor's edema,
      whereas that in the right ear may have resulted from changes in CSF pressure
      caused by the mass effects of the tumor.

PMID- 18340593
TI  - Lifetime suicide attempts in juvenile assessment center youth.
AB  - To describe suicide risk in youth seen at a Juvenile Assessment Center (JAC), we
      examined relationships among self-reported lifetime attempts and demographic,
      justice, and psychiatric data via logistic regression. Similar to other settings,
      youth reporting lifetime attempts were more likely to be older, female, not
      living with both parents and currently arrested for a violent or felony crime.
      Mood, substance use, and behavior disorder each increased prediction
      substantially. Anxiety Disorder was associated with elevated attempt rates for
      boys only. JACs need to develop protocols for identifying suicide risk; further,
      since suicide history predicts future attempts, Anxiety Disordered boys may be at
      particular risk.

PMID- 18340592
TI  - Neurobiology of suicidal behavior. An integration of biological and clinical
      findings.
AB  - Suicide is among the top ten leading causes of death in individuals of all ages.
      An explanatory model for suicidal behavior that links clinical and psychological
      risk factors or endophenotypes, to the underlying neurobiological abnormalities
      associated with suicidal behavior may enhance prediction, help identify treatment
      options and have heuristic value. Our explanatory model proposes that
      developmental factors that are biological (genetics) and psychological or
      clinical (early childhood adversity) may have causal relevance to the
      disturbances found in subjects with suicidal behavior. In this way, our model
      integrates findings from several perspectives in suicidology and attempts to
      explain the relationship between various neurobiological, genetic, and clinical
      observations in suicide research, offering a comprehensive hypothesis to
      facilitate understanding of this complex outcome.

PMID- 18340594
TI  - The relationship between suicidal behavior, ideation, and binge drinking among
      college students.
AB  - Suicidal ideation and behavior among college students are serious and prevalent
      problems that warrant considerable attention. While a variety of situational and
      personality factors have been linked to suicidal behavior, alcohol use is one of
      the most commonly cited factors. As alcohol consumption is a frequent activity
      for many college students, the association between alcohol use and suicidal
      behavior may have particularly lethal consequences for students. Yet, to date,
      few studies have examined the relationship between drinking and suicidal ideation
      and behavior in this population. This study provides empirical support for this
      relationship. That is, significant relationships were found between past alcohol
      use and past suicide attempt(s) and between past binge drinking and past suicidal
      behavior and ideation. The results are discussed in light of their implications
      for intervention with and assessment of students presenting with suicidal
      ideation, behavior, and/or binge drinking.

PMID- 18340595
TI  - Quality of depression among suicidal inpatient youth.
AB  - This study examined the relationship between suicidality and dependent and self
      critical depression among adolescents. Ninety-six adolescents participated: 32
      suicidal inpatients, 32 nonsuicidal inpatients and 32 healthy controls. The
      groups were matched for gender, age and education. Participants completed the
      Depressive Experience Questionnaire for Adolescents (DEQ-A), the Cognition
      Checklist (CCL), and the Multi-Attitude Suicidal Tendencies Scale (MAST). Results
      indicated that suicidal adolescents have significantly higher levels of self
      critical and dependent depression, compared to nonsuicidal inpatients and healthy
      controls. The distinctive quality of depression among suicidal adolescents
      suggests assessment and treatment strategies for these individuals.

PMID- 18340596
TI  - Community study of suicidal behaviors and risk factors among Iranian adults.
AB  - The present study is part of the WHO/SUPRE-MISS conducted in Iran. The aim of the
      study was to determine the lifetime prevalence of suicide behaviors in a
      community sample of Iranian adults. Five hundred and four families were selected
      randomly according to electricity bills in Karaj, 45 km from the capital city,
      represented the catchment area for this investigation. The SUPRE-MISS
      questionnaires used in this study compromised a variety of aspects of suicidal
      behaviors. Lifetime prevalence rates for suicidal ideation, planning and attempts
      were 14%, 6.6%, and 4.1% respectively. Tobacco users and long-term mental and
      physical disabilities were significantly higher among subjects with a history of
      suicidal attempts. Younger ages, tobacco abuse, and long-term mental or physical
      disabilities could be considered risk factors for attempting suicide.

PMID- 18340597
TI  - Evaluation of gatekeeper training for suicide prevention in veterans.
AB  - Clinical providers and "front line" nonclinical staff who work with veterans,
      families, and communities are natural gatekeepers to identify and to refer
      veterans at risk for suicide. A national cohort (n = 602) of community based
      counseling center staff from the U.S. Department of Veterans Affairs (VA)
      participated in an evaluation of a brief standardized gatekeeper training program
      and a scripted behavioral rehearsal practice session. A significant difference in
      knowledge and self efficacy was observed from pre to post (p < .0001) with the
      nonclinicians showing larger effect sizes for knowledge (0.96 vs. 0.42) and self
      efficacy (0.89 vs. 0.41). Gatekeeper training for suicide prevention shows
      promise for increasing the capacity of VA staff to work with at risk veterans.

PMID- 18340598
TI  - Epidemiology of suicide in Pakistan: determining rates in six cities.
AB  - In recent years suicide has become a major public health problem in Pakistan.
      Despite this there are no official statistics on suicide and national rates are
      unknown. To determine rates we carried out an analysis of suicide reports from
      six cities in Pakistan. Rates vary from 0.43/100,000 in Peshawar to 2.86/100,000
      in Rawalpindi. Rates for men are consistently higher than women; highest rates
      for men were 7.06/100,000 between the ages 20-40 years in Larkana, Sindh
      province. Given the legal, socio-cultural, and religious stigma of suicides in
      Pakistan, we believe these figures to be an underestimate. There is urgent need
      for a standard system of recording of suicides in Pakistan, so that true rates
      can be determined. This will help in informing policy and monitoring
      effectiveness of suicide prevention programs.

PMID- 18340599
TI  - The impact of suicidal rock music lyrics on youth: an investigation of individual
      differences.
AB  - This study attempted to predict reactions after listening to music with lyrics
      about suicide. One hundred and twenty-six volunteers completed self-reports of
      personality and mood, and then listened to the music. Afterwards, they completed
      projective stories, self-reports of moods and reactions, and a memory test for
      the lyrics. Low openness to experience, and to a lesser extent, high neuroticism
      and low self-esteem predicted higher levels of suicide-related content in
      projective story-writing, as did knowing a suicide victim. Both the personality
      measures and post-listening mood predicted remembering too many nihilistic
      lyrics. Surprisingly, 68% of participants wrote at least one projective story
      with altruistic content. Individual differences were modestly associated with
      suicidal thoughts after listening to the music.

PMID- 18340600
TI  - Suicide in the Soviet Gulag camps.
AB  - About 18 million Soviet citizens passed through the Gulag system of labor and
      concentration camps between 1929 and 1953. Based upon literary evidence from camp
      survivors and published documents, the authors present reports of attempted
      suicide and completed suicide, along with a discussion of whether suicide in
      Gulag camps was a frequent or rare behavior. Similar to reports from the Nazi
      concentration camps during WWII the existence of Muselmanner or dokhodyagi, the
      dying prisoners emaciated by hunger, sometimes considered as suicides, has been
      identified among the Gulag inmates. Also, the incidence and methods of self
      mutilation among the camp inmates are discussed.

PMID- 18340601
TI  - Are faces special? A case of pure prosopagnosia.
AB  - The ability to recognize individual faces is of crucial social importance for
      humans and evolutionarily necessary for survival. Consequently, faces may be
      "special" stimuli, for which we have developed unique modular perceptual and
      recognition processes. Some of the strongest evidence for face processing being
      modular comes from cases of prosopagnosia, where patients are unable to recognize
      faces whilst retaining the ability to recognize other objects. Here we present
      the case of an acquired prosopagnosic whose poor recognition was linked to a
      perceptual impairment in face processing. Despite this, she had intact object
      recognition, even at a subordinate level. She also showed a normal ability to
      learn and to generalize learning of nonfacial exemplars differing in the nature
      and arrangement of their parts, along with impaired learning and generalization
      of facial exemplars. The case provides evidence for modular perceptual processes
      for faces.

PMID- 18340602
TI  - Animist thinking in the elderly and in patients with Alzheimer's disease.
AB  - Some patients with Alzheimer's disease (AD) reveal low-level impairment in their
      concepts of living things (i.e., forgetting that zebras are striped). To test for
      more profound impairment, we investigated the concept alive--a "higher order"
      concept spanning every member of the domain. Many elderly controls were animists,
      attributing life to inanimates capable of self-generated activity (the sun,
      fire). Most AD patients were animists, with half even attributing life to
      inanimates whose activity is not self-generated (cars, lamps). Adult animists,
      like young children who have not yet acquired biological concepts, overattributed
      life to active inanimates. We believe this reflects an innate disposition to view
      active entities as agents, and that agency interferes with the biological concept
      alive. This interference, we suggest, reflects degradation of biological concepts
      in the face of spared perception of agents. It sheds light on the nature of
      fundamental questions concerning conceptual organization, innate endowment, and
      conceptual change.

PMID- 18340603
TI  - Remediation of developmental dyslexia: tackling a basic memory deficit.
AB  - Remediation studies of developmental dyslexia are extremely rare. We present a
      single case study of an 8-year-old German developmental dyslexic boy K.H. who is
      hypothesized to suffer from a severe memory problem, impeding the development of
      normal reading functions. The memory problem especially affects the storage and
      access to letter-sound associations. As a consequence, the boy was initially
      unable to accurately and quickly name most of the 26 letters of the alphabet. A
      multiple-baseline across-material design with a high-frequency errorless learning
      procedure was set up to improve letter-name associations. The intervention
      improved K.H.'s letter reading and even his word reading. We discuss the role of
      memory deficits in reading acquisition in the context of three different
      theoretical models. We show how such theoretical considerations can successfully
      guide remediation programmes.

PMID- 18340604
TI  - A tale of two agnosias: distinctions between form and integrative agnosia.
AB  - The performance of two patients with visual agnosia was compared across a number
      of tests examining visual processing. The patients were distinguished by having
      dorsal and medial ventral extrastriate lesions. While inanimate objects were
      disadvantaged for the patient with a dorsal extrastriate lesion, animate items
      are disadvantaged for the patient with the medial ventral extrastriate lesion.
      The patients also showed contrasting patterns of performance on the Navon Test:
      The patient with a dorsal extrastriate lesion demonstrated a local bias while the
      patient with a medial ventral extrastriate lesion had a global bias. We propose
      that the dorsal and medial ventral visual pathways may be characterized at an
      extrastriate level by differences in local relative to more global visual
      processing and that this can link to visually based category-specific deficits in
      processing.

PMID- 18340605
TI  - Synaesthesia: the existing state of affairs.
AB  - In synaesthesia one type of stimulation evokes the sensation of another, such as
      when hearing a sound produces photisms--that is, mental percepts of colours. In
      the past, the idiosyncrasy of this phenomenon, as well as the natural mistrust of
      scientists towards the subjective, consigned synaesthesia to the periphery of
      scientific interest. However, the landscape has changed radically in the last two
      decades. The labour of many researchers, inside as well as outside of cognitive
      neuroscience, has transformed synaesthesia into a scientific reality whose
      existence can be demonstrated and studied empirically. The present paper
      summarizes and reflects on our current knowledge concerning synaesthesia in all
      its aspects (cognition, behaviour, neurology, genetics, and demographics).

PMID- 18340606
TI  - Two orienting mechanisms, one architecture: a comment on Rusconi, Turatto and
      Umilta (2007).

PMID- 18340608
TI  - From the editor - girls at risk.

PMID- 18340609
TI  - Neuropsychiatric symptoms of hepatitis C.
AB  - More than 4 million (2%) people in the United States have been infected with the
      hepatitis C virus, of whom 2.7 million are chronically infected. The current
      treatment for chronic hepatitis C patients is Interferon and ribavirin
      combination therapy, which is associated with numerous neuropsychiatric side
      effects. The most common are fatigue, depression, cognitive dysfunction, and
      anxiety. Early identification and treatment of these symptoms may not only
      improve the patient's mental health, but also may increase the patient's
      functional ability and overall quality of life. Psychiatric nurses can play a
      pivotal role in the successful management of the neuropsychiatric symptoms.

PMID- 18340610
TI  - The ward atmosphere of single-sex wards in a maximum-security forensic
      psychiatric hospital in Sweden.
AB  - This exploratory study investigated the ward atmosphere of single-sex wards in a
      forensic psychiatric context in the light of Moos' conceptualization of the
      treatment setting. The wards for female patients bore similarities to
      Relationship-Oriented and Insight-Oriented programmes and had a generally
      positive ward atmosphere. On the other hand the wards for male patients did not
      resemble any treatment programme and had a more mixed diagnosis profile than
      those for female patients. Comparisons of the two types of wards are made and
      implications of the findings in terms of the overriding principle of
      normalization are discussed.

PMID- 18340611
TI  - A comparison of blogs by depressed men and women.
AB  - This paper reports on a study comparing Internet blogs written by 45 men and 45
      women who self-identified as depressed. Using qualitative and inductive methods,
      distinct differences among the male and female experiences of depression were
      documented. Among the most important differences were the distinctions male and
      female bloggers made in regards to (1) the bio-medicalization of depression; (2)
      the relative significance of world events as compared to relationships in
      depression experiences; and (3) violence, including suicide and cutting.
      Theoretical reasons and explanations for these findings are discussed.

PMID- 18340612
TI  - Sense of coherence and quality of life in women family members of the seriously
      mentally ill.
AB  - Providing care to a family member with serious mental illness (SMI) can reduce a
      family's quality of life. Quality of life, however, can be positively influenced
      by the caregiver's sense of coherence (SOC). Antonovsky's Salutogenic Health
      Model was examined in this secondary analysis of data from 60 women family
      members of adults with SMI. The results indicated that greater perceived stress
      decreased SOC and QoL, greater SOC enhanced QoL, and SOC partially mediated the
      effects of perceived stress on QoL. The findings suggest the need for reducing
      stress and strengthening SOC to promote optimal QoL for family members of adults
      with SMI.

PMID- 18340613
TI  - Living without a strong father figure: a context for teen mothers' experience of
      having become sexually active.
AB  - Family dynamics have often been considered central to understanding high risk
      behavior among adolescents. During a phenomenological study of their experiences
      of having become sexually active, ten teen mothers shared their personal stories.
      Some of the information shared represented features of the teens' life-world, or
      the context of their experiences. One feature of the life-world the participants
      described, living without a strong father figure, was seen as an important
      general context for these teens' experiences of having become sexually active.
      While there is evidence in the literature that growing up with an absent father
      is related to early onset of sexual activity, the experience of a father who
      might be present but not emotionally connected to his daughter has not been well
      explored. Therefore, this research offers a richer and deeper perspective on teen
      sexual behavior.

PMID- 18340614
TI  - Impact of physical abuse on adulthood depressive symptoms among women.
AB  - This manuscript provides a systematic review of the literature to examine the
      relationship between childhood physical abuse and intimate partner physical abuse
      with adulthood depressive symptoms among women. Thirty-five studies that targeted
      women, measured depressive symptoms, childhood physical abuse, and intimate
      partner physical abuse were reviewed. Findings indicated an association between
      physical abuse experiences and depressive symptoms. However, the association of
      other risk factors, including other types of abuse, with depressive symptoms
      confounded this relationship. Recommendations, including control for other types
      of abuse, use of valid and reliable measures, and provision of a clear definition
      of physical abuse, are provided.

PMID- 18340615
TI  - Does culture frame adjustment to the sick role?

PMID- 18340616
TI  - The medium, the message, and evidence-based practice.

PMID- 18340619
TI  - Elements of discovery.
AB  - I understand discovery as the essence of thinking man, or to paraphrase the
      notable French philosopher Rene Descartes, "I think, therefore I discover." In
      this study, I introduce discovery as the foundation of modern science. Discovery
      consists of six stages or elements, including: concept, belief, ability, support,
      proof, and protection. Each element is discussed within the context of the whole
      discovery enterprise. Fundamental tenets for understanding discovery are given
      throughout the paper, and a few examples illustrate the significance of some of
      the most important elements. I invite clinicians, researchers, and/or clinical
      researchers to integrate themselves into the active process of discovery.
      Remember--I think, therefore I discover.

PMID- 18340620
TI  - Lessons from the history of medicine.
AB  - What is the point of teaching the history of medicine? Many historians and
      clinicians find it regrettable that some medical students today will graduate
      knowing almost nothing of such "greats" of the past as Hippocrates, Galen,
      Vesalius, Harvey, Lister, and Pasteur. But does this really matter? After all,
      traditional history of medicine curricula tended to distort medicine's past,
      omitting the countless errors, wrong turns, fads, blunders, and abuses, in order
      to tell the sanitized stories of a few scientific superheroes. Modern scholarship
      has seriously challenged most of these heroic dramas; few of our heroes were as
      farsighted, noble, or obviously correct as once thought. Joseph Lister, for
      example, turns out to have had filthy wards, whereas William Harvey was devoted
      to the Aristotelianism he was long said to have overthrown [1]. But as the
      history of medicine has become less romanticized, it has also become much more
      relevant, for it promises to impart useful lessons in the vital importance of
      scientific scepticism.

PMID- 18340621
TI  - Granulocyte colony-stimulating factor increases hepatic sinusoidal perfusion
      during liver regeneration in mice.
AB  - Conditioning with granulocyte colony-stimulating factor (G-CSF) promotes liver
      regeneration in an experimental small-for-size liver remnant mouse model. The
      mechanisms involved in this extraordinary G-CSF effect are unknown. The aim of
      this study was to investigate the influence of G-CSF on the hepatic
      microvasculature in the regenerating liver. The hepatic sinusoidal
      microvasculature and microarchitecture of the regenerating liver were evaluated
      by intravital microscopy in mice. Three experimental groups were compared: (1)
      unoperated unconditioned animals (control; n = 5), (2) animals conditioned with G
      CSF 48 h after 60% partial hepatectomy (G-CSF-PH; n = 6), and (3) animals sham
      conditioned 48 h after 60% PH (sham-PH; n = 6). PH led to hepatocyte hypertrophy
      and increased hepatic sinusoidal velocity in the sham-PH and G-CSF-PH groups.
      Increased sinusoidal diameter and increased hepatic blood flow were observed in
      the G-CSF-PH group compared to the sham-PH and control groups. Furthermore, there
      was a strong positive correlation between spleen weight and hepatic sinusoidal
      diameter in the G-CSF-PH group. The increased hepatic blood flow could explain
      the observed benefit of G-CSF conditioning during liver regeneration. These
      results elucidate an unexplored aspect of pharmacological modulation of liver
      regeneration and motivate further experiments.

PMID- 18340622
TI  - The effect of intraperitoneal catalase on prevention of peritoneal adhesion
      formation in rats.
AB  - The objective of our study was to investigate the efficacy of catalase in
      preventing the formation of peritoneal adhesions induced by cecal serosal
      laceration in rats. A research study was set up using a randomized complete block
      design. This study was performed in the Experimental Surgical Research Center,
      Kahramanmaras Sutcuimam University, Kahramanmaras, Turkey. Thirty Wistar albino
      rats were assigned to 3 groups of 10 animals each. The animals were anesthetized,
      a median laparotomy was performed, and the cecum was traumatized. In the final
      stages of surgery, the first group received 30,000 U of catalase
      intraperitoneally (ip) (catalase group), the second group received 2 mL of saline
      solution ip (isotonic group), and the last group received no treatment (control
      group). All rats were sacrificed on day 14. Adhesions were counted and blood
      samples were taken for measuring the catalase level. There were significant
      differences between the adhesion scores among all groups (p < .05, Kruskal-Wallis
      test). The catalase group had significantly lower adhesion scores than the other
      groups (post hoc Mann-Whitney test). At day 14, blood catalase levels in the
      catalase group were significantly lower than in the other groups (p < .05). We
      conclude that introduction of catalase into the peritoneal cavity during surgery
      inhibited adhesion formation.

PMID- 18340623
TI  - In vitro effectiveness of different chemical agents on scolices of hydatid cyst.
AB  - In the surgical history of hepatic hydatid disease, multiple scolicidal agents
      have been used for sterilization of the cyst contents. However, none of these
      agents can be safely used, because most have unacceptable side effects, such as
      toxicity, caustic sclerosing cholangitis, bile duct stricture, and hypernatremia.
      Protoscolices were aseptically removed from liver hydatid cysts obtained from
      sheep slaughtered at the municipal abattoir in Kahramanmaras, Turkey. In this
      study, the effects of 0.9% NaCl (control group), 20% NaCl (hypertonic saline),
      20% silver nitrate, albendazole 20 mg/cm3, 50% dextrose (hypertonic glucose), and
      20% mannitol and aminomix-1 solutions on echinococe cysts were investigated under
      in vitro conditions. After 5, 10, 15, 20, 25, 30, 45, and 60 min for each
      concentration, the first 100 protoscolices were counted on the 10x microscopical
      field. Protoscolices, which showed positive staining by eosine were considered as
      dead ones. The averages of dead and total protoscolices were calculated. Our
      results showed that all observed protoscolices were dead after the treatments by
      20% silver nitrate in 20 min, by 50% dextrose and by aminomix-1 solution in 30
      min, and by 20% NaCl and by 20% mannitol in 45 min. Albendazole at 20 mg/cm3 was
      observed to lead to death of 65% of protoscolices in the first 5 min and 70% of
      protoscolices at the end of 60 min. Compared with 0.9% NaCl (saline), all of
      these scolicidal agents were significantly effective (p < .05). Aminomix-1, 20%
      mannitol, and 50% dextrose solutions may be used in percutaneous and surgical
      treatment of hydatid cyst. They may be preferred because they are readily
      available, can be administered intravenously, and have an equal or greater
      effectiveness than 20% hypertonic saline.

PMID- 18340624
TI  - Different effects of vertical banded gastroplasty and Roux-en-Y gastric bypass on
      meal inhibition of ghrelin secretion in morbidly obese patients.
AB  - A decrease in ghrelin plasma levels in morbidly obese patients subjected to
      bariatric surgery has been considered to help increase body weight loss.
      Contradictory results have been described after Roux-en-Y gastric bypass (RYGBP),
      and no study to date has compared RYGBP and vertical banded gastroplasty (VBG),
      the two main operations performed in the United States. We investigated the
      effects of RYGBP (10 patients) and VBG (12 patients) on basal and postmeal
      ghrelin plasma levels in 22 morbidly obese patients (20 F and 2 M), mean age 42.1
      +/- 3.7 years, mean weight 115 +/- 3.9 kg, mean body mass index (BMI) 43.5 +/-
      1.7. Before surgery and after a 20% reduction in BMI, ghrelin concentrations
      (pg/mL; radioimmunoassay [RIA], DRG Diagnostics, Germany) were measured in all
      patients 45 min before and for 3 h after a standard liquid meal (Osmolite RTH
      solution, 500 mL, 504 kcal). The results were expressed as mean +/- SD.
      Differences between times and groups were evaluated by Student's t-test and one
      way analysis of variance (ANOVA). We found that basal ghrelin plasma levels were
      reduced after RYGBP (to 73.1 +/- 6 pg/mL, p < .05) but increased after VBG (to
      172 +/- 26 pg/mL, p < .0009). After a standard liquid meal, ghrelin plasma levels
      decreased significantly over 1 h in VBG patients, whereas they remained unchanged
      in RYGBP patients. Since these results were obtained under the same metabolic and
      anthropometric conditions, we conclude that RYGBP acts through permanent
      inhibition of ghrelin secretion, whereas VBG merely restores the mechanisms of
      ghrelin regulation by nutrients.

PMID- 18340625
TI  - Improved preservation of warm ischemic livers by hypothermic machine perfusion
      with supplemented University of Wisconsin solution.
AB  - Hypothermic machine perfusion (HMP) has the potential to improve recovery and
      preservation of Donation after Cardiac Death (DCD) livers, including uncontrolled
      DCD livers. However, current perfusion solutions lack the needed substrates to
      improve energy recovery and minimize hepatic injury, if warm ischemic time (WIT)
      is extended. This proof-of-concept study tested the hypothesis that the
      University of Wisconsin (UW) solution supplemented with anaplerotic substrates,
      calcium chloride, thromboxane A2 inhibitor, and antioxidants could improve HMP
      preservation and minimize reperfusion injury of warm ischemic livers. Preflushed
      rat livers subjected to 60 min WIT were preserved for 5 h with standard UW or
      supplemented UW (SUW) solution. Post preservation hepatic functions and viability
      were assessed during isolated perfusion with Krebs-Henseleit solution. Livers
      preserved with SUW showed significantly (p < .001) improved recovery of tissue
      ATP levels (micromol/g liver), 2.06 +/- 0.10 (mean +/- SE), as compared to the UW
      group, 0.70 +/- 0.10, and the level was 80% of that of fresh control livers (2.60
      +/- 0.13). At the end of 1 h of rewarming, lactate dehydrogenase (U/L) in the
      perfusate was significantly (p < .05) lower in the SUW group (429 +/- 58) as
      compared to ischemia-reperfusion (IR) (781 +/- 12) and the UW group (1151 +/-
      83). Bile production (microg/min/g liver) was significantly (p < .05) higher in
      the SUW group (280 +/- 13) as compared to the IR (224 +/- 24) and the UW group
      (114 +/- 14). The tissue edema formation assessed by tissue wet-dry ratio was
      significantly (p < .05) higher in UW group. Histology showed well-preserved
      hepatic structure in the SUW group. In conclusion, this study suggests that HMP
      with SUW solution has the potential to restore and preserve livers with extended
      WIT.

PMID- 18340626
TI  - Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and
      trastuzumab.
AB  - PURPOSE: The aim of this study was to analyse the suspected adverse reactions
      associated with rituximab or trastuzumab reported to the Spanish
      Pharmacovigilance System. METHODS: From this national database, we selected the
      spontaneous reports registered between 1 January 1999 and 1 June 2006 and
      analysed both age and gender of the patient, the dose prescribed, the severity of
      the report, the evolution, the latency and recovery periods of the adverse
      reaction, the reporting odds ratio (ROR) and the presence of other suspected
      drugs. RESULTS: From 49 927 records registered in the period of analysis, 69 were
      associated with rituximab and 23 with trastuzumab. White cell disorders (n = 18),
      hypotension (n = 7), dyspnoea (n = 6) and pneumonitis (n = 4) were the most
      common adverse reactions associated with rituximab. The mean latency period of
      white cell disorders was 20.9 +/- 7.8 days, except in two cases where it was
      clearly longer (87 +/- 13 days). Hypotension and dyspnoea appeared immediately or
      a few days after the administration of the drug, and rapidly resolved.
      Pneumonitis seems to be a delayed adverse reaction, which required on average, 3
      months to develop. Cardiac failure was the adverse reaction more frequently
      associated with trastuzumab (n = 7). In five of the seven cases of cardiac
      failure reported patients had been taking other suspected medications.
      CONCLUSION: Our results are consistent with the safety profile of rituximab and
      trastuzumab observed in large randomised clinical trials.

PMID- 18340627
TI  - Comparison between pulsed-wave Doppler- and tissue Doppler-derived Tei indices in
      fetuses with and without congenital heart disease.
AB  - OBJECTIVES: The aim of this study was to compare the right (RV) and left (LV)
      ventricular Tei indices obtained by pulsed-wave Doppler (PD) and tissue Doppler
      (TD) methods in fetuses with structurally normal and abnormal hearts. METHODS:
      This was a retrospective cross-sectional study of 147 fetuses that had a fetal
      echocardiogram and Tei index measured during a 2-year period. The RV and LV Tei
      indices were measured using both PD and TD methods. The difference between the
      two methods of Tei index measurement was tested using paired sample t-test,
      Pearson correlation coefficient was used to examine their relationship, and the
      agreement between the methods was tested using Bland-Altman analysis. RESULTS: A
      total of 87 fetuses had normal hearts and 60 had a congenital heart defect. Both
      PD and TD Tei indices were measured successfully from at least one ventricle in
      123 cases and from both ventricles in 110 cases. The mean TD Tei index was
      significantly higher than the mean PD Tei index for both ventricles (P < 0.0001).
      There was a weak but statistically significant correlation between the PD and TD
      Tei indices of the right ventricle (r = 0.20, P = 0.029), whereas the PD and TD
      Tei indices of the left ventricle did not correlate significantly (r = 0.04, P =
      0.684). When pairs of Tei indices measured by two different methods (123 pairs
      for the right ventricle and 111 for the left ventricle) were tested with Bland
      Altman analysis, the bias and precision were 0.147 and 0.254, respectively, for
      the right ventricle, and 0.299 and 0.276, respectively, for the left ventricle.
      CONCLUSIONS: Correlation between Tei indices measured by PD and TD methods is
      weak and the agreement between individual measurements is poor. Therefore, they
      should not be used interchangeably in the assessment of fetal cardiac function.

PMID- 18340628
TI  - Proteomic analysis of wheat proteins recognized by IgE antibodies of allergic
      patients.
AB  - Wheat belongs to six major food allergens inducing IgE-mediated hypersensitivity
      reaction manifesting as cutaneous, gastrointestinal, and respiratory symptoms.
      Although cereals are a staple food item in most diets, only a few wheat proteins
      causing hypersensitivity have been identified. To characterize wheat allergens,
      salt-soluble wheat extracts were separated by 1-DE and 2-DE and IgE-binding
      proteins were detected by immunoblotting using sera of patients with allergy to
      ingested wheat. Proteins, frequently recognized by IgE on 2-DE were analyzed by
      MALDI-TOF and QTOF and their spectrum was completed by 1-DE and LCQ(DECA) nLC
      MS/MS IT technique. Using all three techniques we identified 19 potential wheat
      allergens such as alpha-amylase inhibitors, beta-amylase, profilin, serpin, beta
      D-glucan exohydrolase, and 27K protein. Employing newly developed ELISA, levels
      of IgE Abs against Sulamit wheat extract and alpha-amylase inhibitors type 1 and
      3 were quantified and shown to be significantly elevated in sera of allergic
      patients compared to those of healthy controls. The level of IgE Abs against
      alpha-amylase inhibitor type 3 was lower, slightly above the cut-off value in the
      majority of patients' sera. Our findings contribute to the identification of
      wheat allergens aimed to increase the specificity of serum IgE and cell
      activation diagnostic assays.

PMID- 18340629
TI  - Variability of polymorphic families of three types of xylanase inhibitors in the
      wheat grain proteome.
AB  - Cereals contain proteinaceous inhibitors of endo-beta-1,4-xylanases (E.C.3.2.1.8,
      xylanases). Since these xylanase inhibitors (XIs) are only active against
      xylanases of microbial origin and do not interact with plant endogenous
      xylanases, they are believed to act as a defensive barrier against
      phytopathogenic attack. So far, three types of XIs have been identified, i.e.
      Triticum aestivum XI (TAXI), xylanase inhibiting protein (XIP), and thaumatin
      like XI (TLXI) proteins. In this study the variation in XI forms present in wheat
      grain was elucidated using high-resolution 2-DE in combination with LC-ESI-MS/MS
      and biochemical techniques. Reproducible 2-DE fingerprints of TAXI-, XIP-, and
      TLXI-type XIs, selectively purified from whole meal of three European wheat
      cultivars using cation exchange chromatography followed by affinity
      chromatography, were obtained using a pH-gradient of 6 to 11 and a molecular mass
      range of 10 to 60 kDa. Large polymorphic XI families, not known to date, which
      exhibit different pI- and/or molecular mass values, were visualised by colloidal
      CBB staining. Identification of distinct genetic variants by MS/MS-analysis
      provides a partial explanation for the observed XI heterogeneity. Besides genetic
      diversity, PTMs, such as glycosylation, account for the additional complexity of
      the 2-DE patterns.

PMID- 18340630
TI  - Protein expression profile of Gluconacetobacter diazotrophicus PAL5, a sugarcane
      endophytic plant growth-promoting bacterium.
AB  - This is the first broad proteomic description of Gluconacetobacter
      diazotrophicus, an endophytic bacterium, responsible for the major fraction of
      the atmospheric nitrogen fixed in sugarcane in tropical regions. Proteomic
      coverage of G. diazotrophicus PAL5 was obtained by two independent approaches: 2
      DE followed by MALDI-TOF or TOF-TOF MS and 1-DE followed by chromatography in a
      C18 column online coupled to an ESI-Q-TOF or ESI-IT mass spectrometer. The 583
      identified proteins were sorted into functional categories and used to describe
      potential metabolic pathways for nucleotides, amino acids, carbohydrates, lipids,
      cofactors and energy production, according to the Enzyme Commission of Enzyme
      Nomenclature (EC) and Kyoto Encyclopedia of genes and genomes (KEGG) databases.
      The identification of such proteins and their possible insertion in conserved
      biochemical routes will allow comparisons between G. diazotrophicus and other
      bacterial species. Furthermore, the 88 proteins classified as conserved unknown
      or unknown constitute a potential target for functional genomic studies, aiming
      at the understanding of protein function and regulation of gene expression. The
      knowledge of metabolic fundamentals and coordination of these actions are crucial
      for the rational, safe and sustainable interference on crops. The entire dataset,
      including peptide sequence information, is available as Supporting Information
      and is the major contribution of this work.

PMID- 18340631
TI  - Involvement of post-translational modification of neuronal plasticity-related
      proteins in hyperalgesia revealed by a proteomic analysis.
AB  - To clarify roles of an endogenous pain modulatory system of the central nervous
      system (CNS) in hyperalgesia, we tried to identify qualitative and quantitative
      protein changes by a proteomic analysis using an animal model of hyperalgesia.
      Specifically, we first induced functional hyperalgesia on male Wistar rats by
      repeated cold stress (specific alternation of rhythm in temperature, SART). We
      then compared proteomes of multiple regions of CNS and the dorsal root ganglion
      between the hyperalgetic rats and non-treated ones by 2-D PAGE in the pI range of
      4.0-7.0. We found that SART changed the proteomes prominently in the
      mesencephalon and cerebellum. We thus analyzed the two brain regions in more
      detail using gels with narrower pI ranges. As a result, 29 and 23 protein spots
      were significantly changed in the mesencephalon and the cerebellum, respectively.
      We successfully identified 12 protein spots by a MALDI-TOF/TOF MS and subsequent
      protein database searching. They included unc-18 protein homolog 67K, collapsin
      response mediator protein (CRMP)-2 and CRMP-4, which were reported to be involved
      in neurotransmitter release or axon elongation. Interestingly, mRNA expression
      levels of these three proteins were not changed significantly by the induction of
      hyperalgesia. Instead, we found that the detected changes in the protein spots
      are caused by the post-translational modification (PTM) of proteolysis or
      phosphorylation. Taken together, development of the hyperalgesia would be linked
      to PTM of these three CNS proteins. PTM regulation may be one of the useful ways
      to treat hyperalgesia.

PMID- 18340632
TI  - Detailed proteome analysis of growing cells of the planctomycete Rhodopirellula
      baltica SH1T.
AB  - Rhodopirellula baltica SH1(T), which was isolated from the water column of the
      Kieler Bight, a bay in the southwestern Baltic Sea, is a marine aerobic,
      heterotrophic representative of the ubiquitous bacterial phylum Planctomycetes.
      We analyzed the R. baltica proteome by applying different preanalytical protein
      as well as peptide separation techniques (1-D and 2-DE, HPLC separation) prior to
      MS. That way, we could identify a total of 1115 nonredundant proteins from the
      intracellular proteome and from different cell wall protein fractions. With the
      contribution of 709 novel proteins resulting from this study, the current
      comprehensive R. baltica proteomic dataset consists of 1267 unique proteins
      (accounting for 17.3% of the total putative protein-coding ORFs), including 261
      proteins with a predicted signal peptide. The identified proteins were
      functionally categorized using Clusters of Orthologous Groups (COGs), and their
      potential cellular locations were predicted by bioinformatic tools. A unique
      protein family that contains several YTV domains and is rich in cysteine and
      proline was found to be a component of the R. baltica proteinaceous cell wall.
      Based on this comprehensive proteome analysis a global schema of the major
      metabolic pathways of growing R. baltica cells was deduced.

PMID- 18340633
TI  - The mouse sperm proteome characterized via IPG strip prefractionation and LC
      MS/MS identification.
AB  - Proteomic profiling of the mouse spermatozoon has generated a unique and valuable
      inventory of candidates that can be mined for potential contraceptive targets and
      to further our understanding of the PTMs that regulate the functionality of this
      highly specialized cell. Here we report the identification of 858 proteins
      derived from mouse spermatozoa, 23 of which demonstrated testis only expression.
      The list contained many proteins that are known constituents of murine
      spermatozoa including Izumo, Spaca 1, 3, and 5, Spam 1, Zonadhesin, Spesp1, Smcp,
      Spata 6, 18, and 19, Zp3r, Zpbp 1 and 2, Spa17, Spag 6, 16, and 17, CatSper4,
      Acr, Cylc2, Odf1 and 2, Acrbp, and Acrv1. Certain protein families were highly
      represented in the proteome. For example, of the 42 gene products classified as
      proteases, 26 belonged to the 26S-proteasome. Of the many chaperones identified
      in this proteome, eight proteins with a TCP-1 domain were found, as were seven
      Rab guanosine triphosphatases. Finally, our list yielded three putative seven
      transmembrane proteins, two of which have no known tissue distribution, an
      extragenomic progesterone receptor and three unique testis-specific kinases all
      of which may have some potential in the future regulation of male fertility.

PMID- 18340634
TI  - A simple and highly successful C-terminal sequence analysis of proteins by mass
      spectrometry.
AB  - A simple and efficient method for C-terminal sequencing of proteins has long been
      pursued because it would provide substantial information for identifying the
      covalent structure, including post-translational modifications. However, there
      are still significant impediments to both direct sequencing from C termini of
      proteins and specific isolation of C-terminal peptides from proteins. We describe
      here a highly successful, de novo C-terminal sequencing method of proteins by
      employing succinimidyloxycarbonylmethyl tris (2,4,6-trimethoxyphenyl) phosphonium
      bromide and mass spectrometry.

PMID- 18340635
TI  - Proteomic analysis of hearts from frataxin knockout mice: marked rearrangement of
      energy metabolism, a response to cellular stress and altered expression of
      proteins involved in cell structure, motility and metabolism.
AB  - A frequent cause of death in Friedreich's ataxia patients is cardiomyopathy, but
      the molecular alterations underlying this condition are unknown. We performed 2
      DE to characterize the changes in protein expression of hearts using the muscle
      creatine kinase frataxin conditional knockout (KO) mouse. Pronounced changes in
      protein expression profile were observed in 9 week-old KO mice with severe
      cardiomyopathy. In contrast, only several proteins showed altered expression in
      asymptomatic 4 week-old KO mice. In hearts from frataxin KO mice, components of
      the iron-dependent complex-I and -II of the mitochondrial electron transport
      chain and enzymes involved in ATP homeostasis (creatine kinase, adenylate kinase)
      displayed decreased expression. Interestingly, the KO hearts exhibited increased
      expression of enzymes involved in the citric acid cycle, catabolism of branched
      chain amino acids, ketone body utilization and pyruvate decarboxylation. This
      constitutes evidence of metabolic compensation due to decreased expression of
      electron transport proteins. There was also pronounced up-regulation of proteins
      involved in stress protection, such as a variety of chaperones, as well as
      altered expression of proteins involved in cellular structure, motility and
      general metabolism. This is the first report of the molecular changes at the
      protein level which could be involved in the cardiomyopathy of the frataxin KO
      mouse.

PMID- 18340636
TI  - Precision enhancement of MALDI-TOF MS using high resolution peak detection and
      label-free alignment.
AB  - We have developed an automated procedure for aligning peaks in multiple TOF
      spectra that eliminates common timing errors and small variations in spectrometer
      output. Our method incorporates high-resolution peak detection, re-binning, and
      robust linear data fitting in the time domain. This procedure aligns label-free
      (uncalibrated) peaks to minimize the variation in each peak's location from one
      spectrum to the next, while maintaining a high number of degrees of freedom. We
      apply our method to replicate pooled-serum spectra from multiple laboratories and
      increase peak precision (t/sigma(t)) to values limited only by small random
      errors (with sigma(t) less than one time count in 89 out of 91 instances, 13
      peaks in seven datasets). The resulting high precision allowed for an order of
      magnitude improvement in peak m/z reproducibility. We show that the CV for m/z is
      0.01% (100 ppm) for 12 out of the 13 peaks that were observed in all datasets
      between 2995 and 9297 Da.

PMID- 18340637
TI  - Familial mediterranean fever gene (MEVF) mutations in Crohn's disease in a
      Mediterranean area.

PMID- 18340638
TI  - Azathioprine-induced suicidal erythrocyte death.
AB  - BACKGROUND: Azathioprine is widely used as an immunosuppressive drug. The side
      effects of azathioprine include anemia, which has been attributed to bone marrow
      suppression. Alternatively, anemia could result from accelerated suicidal
      erythrocyte death or eryptosis, which is characterized by exposure of
      phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage.
      METHODS: The present experiments explored whether azathioprine influences
      eryptosis. According to annexin V binding, erythrocytes from patients indeed
      showed a significant increase of PS exposure within 1 week of treatment with
      azathioprine. In a second series, cytosolic Ca2+ activity (Fluo3 fluorescence),
      cell volume (forward scatter), and PS-exposure (annexin V binding) were
      determined by FACS analysis in erythrocytes from healthy volunteers. RESULTS:
      Exposure to azathioprine (> or =2 microg/mL) for 48 hours increased cytosolic
      Ca2+ activity and annexin V binding and decreased forward scatter. The effect of
      azathioprine on both annexin V binding and forward scatter was significantly
      blunted in the nominal absence of extracellular Ca2+. CONCLUSIONS: Azathioprine
      triggers suicidal erythrocyte death, an effect presumably contributing to
      azathioprine-induced anemia.

PMID- 18340639
TI  - Ex vivo simulation of IgG Fc and T-cell receptor functions: an application to
      inflammatory bowel disease.
AB  - BACKGROUND: Human leukocyte IgG Fc receptors (FcgammaR) and T-cell receptors
      (TCR) are primary molecules involved in inflammatory and immune pathways.
      METHODS: These 2 receptors were stimulated in whole blood for 2-4 hours with
      immune complex and specific agonistic antibody, respectively, and various mRNAs
      were quantified by a method we developed previously. RESULTS: FcgammaR
      stimulation induced tumor necrosis factor superfamily 2 (TNFSF2), TNFSF8,
      TNFSF15, interleukin 1B (IL1B), IL8, CCL chemokine 2 (CCL2), CCL3, CCL4, CCL11,
      CCL20, CXCL chemokine 1 (CXCL1), CXCL2, and CXCL3 mRNA, whereas TCR stimulation
      induced different subsets of mRNA such as TNFSF1, TNFSF2, TNFSF5, TNFSF6, TNFSF9,
      TNFSF14, IL6, CCL2, CCL8, CCL20, and CXCL10. Interestingly, respondents and
      nonrespondents were identified for each mRNA. When we applied this method to
      inflammatory bowel disease, the respondent populations of TCR-induced TNFSF2 (=
      TNFalpha), TNFSF5, TNFSF14, CCL2, CCL8, and CCL20 mRNA were significantly higher
      in Crohn's disease (CD) patients than in healthy controls or those with
      ulcerative colitis (UC). No difference was found for FcgammaR-mediated responses.
      The respondent population of TCR-induced TNFSF2 showed significantly (P = 0.05)
      higher incidence of multiple surgeries than did nonrespondents. CONCLUSIONS:
      These data demonstrate an underlining hyperfunction of TCR in peripheral-blood
      leukocytes in CD patients. The ex vivo simulation demonstrates an underlining
      hyperfunction of TCR in peripheral-blood leukocytes in CD patients and may form
      the basis of a relatively noninvasive test for distinguishing these IBDs.

PMID- 18340640
TI  - Do inflammatory bowel disease and cancer share susceptibility: a family study.

PMID- 18340641
TI  - Therapeutic benefit of pentostatin in severe IL-10-/- colitis.
AB  - BACKGROUND: Pentostatin, an adenosine deaminase (ADA) inhibitor, is a purine
      antimetabolite used for the treatment of leukemias. ADA inhibition blunts
      expansion of proliferating lymphocytes and increases adenosine release, a potent
      anti-inflammatory molecule. Human inflammatory bowel disease (IBD) is driven by
      expansion of effector T cells (T(eff)) that overwhelm reulatory T cells (T(reg))
      and propagate innate immune reponses. Here we study the therapeutic benefits of
      ADA inhibition to impair T(eff) cell expansion and reduce inflammatory cytokine
      release in IL-10-deficient (IL-10-/-) mice. METHODS: Colitis was induced in IL-10
      /- mice by administering piroxicam for two weeks. Mice were treated with daily
      pentostatin or phosphate-buffered saline for 1 week and effects on tissue
      inflammation, lymphocyte numbers and cytokine production examined. RESULTS:
      Pentostatin reduced inflammation by >50% and nearly normalized serum amyloid A
      levels. Lymphocyte expansions in the colon and mesenteric lymph node (MLN) (3.5
      fold and >5-fold respectively) dropped by >50-90%. Pro-inflammatory factors in
      the colon and MLN (IL-1beta, IFN-gamma, IL-6, CXCL10, TNF) dropped whereas FoxP3
      and TGF-beta were unchanged. Reductions in cytokine production from equivalent
      numbers of T cells from pentostatin-treated mice after in vitro (36h) or in vivo
      (3h) activation suggested anti-inflammatory effects of pentostatin independent of
      lymphodepletion contributed to its therapeutic benefit. Analysis of mucosal
      lymphocyte subsets suggested pentostatin reduced numbers of effector CD4+ CD69+ T
      cells, while sparing CD4+ CD62L+ T cells. CONCLUSIONS: Pentostatin dosages that
      avoid severe lymphocyte depletion effectively treat colitis by impairing T(eff)
      cell expansion and reducing pro-inflammatory cytokine production while preserving
      regulatory T(reg) populations and function.

PMID- 18340642
TI  - X-inactivation reveals epigenetic anomalies in most hESC but identifies sublines
      that initiate as expected.
AB  - The clinical and research value of human embryonic stem cells (hESC) depends upon
      maintaining their epigenetically naive, fully undifferentiated state.
      Inactivation of one X chromosome in each cell of mammalian female embryos is a
      paradigm for one of the earliest steps in cell specialization through formation
      of facultative heterochromatin. Mouse ES cells are derived from the inner cell
      mass (ICM) of blastocyst stage embryos prior to X-inactivation, and cultured
      murine ES cells initiate this process only upon differentiation. Less is known
      about human X-inactivation during early development. To identify a human ES cell
      model for X-inactivation and study differences in the epigenetic state of hESC
      lines, we investigated X-inactivation in all growth competent, karyotypically
      normal, NIH approved, female hESC lines and several sublines. In the vast
      majority of undifferentiated cultures of nine lines examined, essentially all
      cells exhibit hallmarks of X-inactivation. However, subcultures of any hESC line
      can vary in X-inactivation status, comprising distinct sublines. Importantly, we
      identified rare sublines that have not yet inactivated Xi and retain competence
      to undergo X-inactivation upon differentiation. Other sublines exhibit defects in
      counting or maintenance of XIST expression on Xi. The few hESC sublines
      identified that have not yet inactivated Xi may reflect the earlier epigenetic
      state of the human ICM and represent the most promising source of NIH hESC for
      study of human X-inactivation. The many epigenetic anomalies seen indicate that
      maintenance of fully unspecialized cells, which have not formed Xi facultative
      heterochromatin, is a delicate epigenetic balance difficult to maintain in
      culture.

PMID- 18340643
TI  - High throughput FRET screening of the plasma membrane based on TIRFM.
AB  - Monitoring protein function with high throughput at individual cell level is of
      high interest both for basic research and diagnostic applications. For this,
      following the changes in fluorescence resonance energy transfer (FRET) between a
      donor/acceptor pair, genetically encoded in the proteins of interest, is a
      frequently used tool. As proteins attached to or located in the plasma membrane
      represent a considerable fraction of total proteins, there is a need for high
      throughput imaging techniques suited for observation of proteins in the cell
      membrane only. A system is presented, which allows rapid imaging of large areas
      via total internal reflection fluorescence microscopy (TIRFM) conditions, using a
      focus-hold system, multiwavelength excitation and dual color detection. The
      developed imaging system enables screening of large numbers of cells under TIRFM
      illumination combined with FRET imaging, thereby providing the means to record,
      e.g., FRET-efficiency of a membrane-associated protein labeled with a donor
      acceptor pair. The capability of the system to perform live-FRET scanning with
      TIRFM on stoichiometric FRET constructs, reaching throughput of up to 1,000
      cells/s at the optical resolution limit is demonstrated. A comparison with
      confocal microscopy shows that TIRFM offers a 4.2-fold advantage in our
      conditions over confocal microscopy in detecting contributions from membrane
      localized proteins.

PMID- 18340644
TI  - Global rates of Crohn's disease.

PMID- 18340645
TI  - A multifunctional androgen receptor screening assay using the high-throughput
      Hypercyt flow cytometry system.
AB  - The androgen receptor (AR) is a steroid hormone receptor which regulates
      transcription of androgen-sensitive genes and is responsible for the development
      and maintenance of male secondary sexual characteristics. Chemicals that
      interfere with AR activity may lead to pathological conditions in androgen
      sensitive tissues. A variety of reporter systems have been developed, driven by
      androgen-sensitive promoters, which screen for chemicals that modulate androgenic
      activity. We have developed a flexible, high-throughput AR transcriptional
      activation assay, designated the Multifunctional Androgen Receptor Screening
      (MARS) assay, to facilitate the identification of novel modulators of AR
      transcriptional activity using flow cytometry. Androgen-independent human
      prostate cancer-derived PC3 cells were transiently cotransfected with an
      expression vector for the wild-type human AR and an androgen-sensitive promoter
      regulating the expression of destabilized enhanced GFP (dsEGFP). The transfected
      cells were stimulated with established androgenic and antiandrogenic compounds
      and assessed for increased or decreased dsEGFP expression. To screen for
      antagonists of AR transcription, the AR agonist R1881 was coadministered at
      submaximal concentrations with potential AR antagonists. The assay was formatted
      for high-throughput screening using the HyperCyt flow cytometry system. Agents
      with established androgenic and antiandrogenic activity were used for validation
      of the MARS assay. AR agonists were found to potently induce dsEGFP. Furthermore,
      AR agonists induced dsEGFP expression in a dose-dependent manner. Alternatively,
      AR antagonists blocked dsEGFP expression when coadministered with low-dose R1881,
      which also occurred in a dose-dependent manner. Modulators of AR transcriptional
      activity can be successfully identified by the MARS assay, utilizing a rapid,
      flexible, sensitive, and high-throughput format. Dose-response curves can be
      successfully generated for these compounds, allowing for an assessment of
      potency. Because of its simplicity and high-throughput compatibility, the MARS
      assay and HyperCyt system combined with flow cytometric analysis represents a
      valuable and novel addition to the current repertoire of AR transcriptional
      activation screening assays.

PMID- 18340646
TI  - Seeing through protein complexes by high-throughput FRET.

PMID- 18340647
TI  - Population-based case-control study of alpha 1-antitrypsin and SLC11A1 in Crohn's
      disease and ulcerative colitis.
AB  - BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are chronic
      inflammatory diseases of the digestive tract. Genetic factors and an abnormal
      immune response to infections are suspected to be involved in inflammatory bowel
      diseases. METHODS: In the present study 300 blood samples from CD patients (n =
      100), UC patients (n = 100), and healthy controls (n = 100) were taken from a
      population-based case-control study. PCR assays and capillary electrophoresis
      were used to detect alpha 1 antitrypsin M, S, and Z alleles and the C-to-T
      transition at the -237 nucleotide position of the SLC11A1 promoter. Additionally,
      length polymorphism of (gt)n alleles in the promoter region and TGTG and CAAA
      insertion/deletion in the untranslated region (3' UTR) of the SLC11A1 gene were
      evaluated. RESULTS: The Z allele only for AAT was associated (P < 0.05) with CD.
      No other significant results were detected for AAT alleles. For SLC11A1, alleles
      1 and 2 were significant (P < 0.05) for UC, but only allele 3 was significant (P
      < 0.05) for CD. There was a significant (P < 0.05) association of a CAAA
      insertion with CD but not for deletion in the 3' UTR. No differences (P < 0.05)
      were detected for TAAA. CONCLUSIONS: Because AAT and SLC11A1 proteins directly or
      indirectly function as inhibitors of human leukocyte elastase, mutations in the
      AAT and SLC11A1 genes may change the balance between elastase produced by
      leukocytes during phagocytosis.

PMID- 18340648
TI  - Reduced responsiveness of HLA-B27 transgenic rat cells to TGF-beta and IL-10
      mediated regulation of IFN-gamma production.
AB  - BACKGROUND: We have reported that commensal luminal bacterial components induce
      an active in vitro IFN-gamma response in mesenteric lymph node (MLN) and
      intestinal cells from specific pathogen-free (SPF) HLA-B27 transgenic (TG) rats
      with chronic colitis but not in cells from non-diseased SPF non-TG, germ-free
      (GF) non-TG or GF TG rats. METHODS: The study examined IL-12 stimulation of MLN
      IFN-gamma responses to luminal bacteria and regulation of these responses by
      suppressive cytokines. RESULTS: Exogenous IL-12 significantly increased the
      bacterial lysate-induced IFN-gamma response in SPF TG MLN cells, while bacterial
      lysate and IL-12 synergistically induced IFN-gamma from low baseline levels in
      cells obtained from both SPF and GF non-TG rats, and in GF TG cells. TGF-beta
      fully counteracted the effects of IL-12 and bacterial lysate on non-TG cells by
      almost completely inhibiting IFN-gamma production. In contrast, TG cells were
      less responsive to TGF-beta-mediated downregulation with a substantial residual
      IFN-gamma response to IL-12 plus bacterial lysate. Further experiments showed
      that CD4+/CD25+ cells had no inhibitory effect on the IFN-gamma production and
      were not required for TGF-beta-mediated suppression. Addition of exogenous IL-10
      also partially inhibited IFN-gamma production by non-TG cells but did not affect
      TG cells. Conversely, exogenous IL-12 preferentially suppressed bacterial lysate
      induced TGF-beta and IL-10 production in TG rat cells. CONCLUSIONS: An attenuated
      response to regulatory signals leads to uncontrolled potentiated induction of
      effector IFN-gamma responses to commensal bacteria in HLA-B27 TG rats that
      spontaneously develop chronic intestinal inflammation.

PMID- 18340650
TI  - Low and adequately dosed 6-thioguanine: not so bad after all.

PMID- 18340649
TI  - Role for epithelial dysregulation in early-onset colitis-associated colon cancer
      in Gi2-alpha-/- mice.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a risk factor for developing
      colorectal cancer but the mechanisms are poorly characterized. Mice lacking the G
      protein alpha subunit Gi2-alpha spontaneously develop colitis and colon cancer
      with high penetrance. Compared to canonical Wnt/APC signaling-based animal models
      of colon cancer, the tumors in Gi2-alpha-/- mice more closely recapitulate the
      features of IBD-associated cancers seen in humans. They are predominantly right
      sided, multifocal, mucinous, and arise from areas of flat dysplasia. METHODS: In
      evaluating the potential contribution of epithelial Gi2-alpha signaling to this
      phenotype, we found that Gi2-alpha-/- colonic epithelium is hyperproliferative
      even before the onset of colitis, and resistant to the induction of apoptosis. We
      generated colon cancer cell lines overexpressing dominant-negative Gi2-alpha.
      RESULTS: Like other cells lacking Gi2-alpha, these cells release less arachidonic
      acid, an important antiinflammatory and epithelial growth regulator. They are
      also hyperproliferative and resistant to camptothecin-induced apoptosis and
      caspase-3 activation. CONCLUSIONS: The colitis-associated cancers in Gi2-alpha-/-
      mice appear very similar to those seen in human IBD patients, and Gi2-alpha is a
      direct negative regulator of colonic epithelial cell growth.

PMID- 18340651
TI  - Glyphosate-resistant weeds and crops. Editorial.

PMID- 18340653
TI  - STEALTH in transplantation tolerance.

PMID- 18340652
TI  - Practice makes perfect: a volume-outcome study of hospital patients with HIV
      disease.
AB  - OBJECTIVE: There is considerable evidence that patients with HIV fare better in
      hospitals that treat more HIV-positive patients. Yet, it is possible that much of
      this benefit is attributable to the care provided by physicians who treat high
      volumes of HIV-positive patients. This study examines the relation between 2
      measures of volume (the number of HIV-positive patients treated in a hospital and
      the number of HIV-positive patients treated by the attending physician) and the
      probability of dying in the hospital. DATA: This study uses discharge data from
      43,325 patients hospitalized with HIV disease in 5 states (Colorado, Maryland,
      New Jersey, New York, and Washington State) in 2002. These data were obtained
      from the Agency for Healthcare Research and Quality's Healthcare Cost and
      Utilization Project State Inpatient Databases. STUDY DESIGN: Volume-outcome
      studies have demonstrated an inverse relation between the number of HIV-positive
      patients treated at a hospital and the mortality rate for these patients. Yet,
      the most current of these studies is based on data more than a decade old, and
      none of these account for the volume of HIV-positive patients treated by the
      physician. This study uses multivariate logistic regression analyses to estimate
      the impact of hospital and physician volume on patient mortality. RESULTS: This
      study found that when measures of physician and hospital volume are included in a
      regression equation explaining patient mortality, only the variable measuring
      physician volume remains statistically significant. Moreover, when a variable is
      defined for each patient based on the quartile rankings of the patient's hospital
      volume and the patient's physician volume, the quartile ranking of physician
      volume is a better predictor of survival than the quartile ranking of hospital
      volume. CONCLUSION: These findings suggest that the volume of patients treated by
      the attending physician is the key measure of volume associated with the survival
      of hospitalized HIV-positive patients.

PMID- 18340654
TI  - HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco,
      and Los Angeles, 2004 to 2005.
AB  - BACKGROUND: Syphilis outbreaks among men who have sex with men (MSM) in the
      United States have raised concerns about increased HIV transmission in this
      population. We sought to estimate HIV incidence among men diagnosed with primary
      or secondary (P&S) syphilis in sexually transmitted disease (STD) clinics in
      Atlanta, San Francisco, and Los Angeles. METHODS: We analyzed deidentified
      sociodemographic information from routine syphilis surveillance databases and
      matching remnant sera from consecutive male patients with P&S syphilis who were
      tested for syphilis at 3 public health laboratories during January 2004 through
      January 2006. Deidentified sera positive for Treponema pallidum by particle
      agglutination were screened for HIV-1 antibodies by enzyme immunoassay (EIA).
      Specimens that were confirmed HIV-positive by Western blot analysis were then
      tested for recent HIV infection using the less sensitive (LS) HIV-1 Vironostika
      EIA and BED HIV-specific IgG/total IgG assay. RESULTS: Of 357 men with P&S
      syphilis (98 in Atlanta, 151 in San Francisco, and 108 in Los Angeles), 32% had
      primary syphilis and 85% were MSM (12% no MSM risk and 3% no information). The
      median age was 36 years; 40% were white, 31% black, 20% Hispanic, and 8% other.
      Among men with P&S syphilis, 160 (45%) were HIV-positive, of whom 8 were
      classified as having acquired recent HIV infection by the LS-Vironostika EIA (all
      confirmed by BED) and had no history of antiretroviral use or HIV-positive
      results >6 months earlier. Seven of the 8 men with recent HIV infection were MSM.
      The estimated HIV incidence was 9.5% per year (95% confidence interval [CI]: 2.9
      to 16.0) among all men and 10.5% per year (95% CI: 2.7 to 18.3) among MSM.
      CONCLUSIONS: We found high HIV incidence among a high-risk population of US men
      diagnosed with P&S syphilis in STD clinics in Atlanta, San Francisco, and Los
      Angeles. Intensive integrated HIV/STD prevention programs are needed for this
      population.

PMID- 18340655
TI  - Proceedings of the 20th Annual Conference of the European Macrophage and
      Dendritic Cell Society, Freiburg, Germany, October 5-7, 2006.

PMID- 18340656
TI  - Limited knowledge and use of HIV post- and pre-exposure prophylaxis among gay and
      bisexual men.
AB  - BACKGROUND: Post-exposure prophylaxis (PEP) is currently recommended after
      certain high-risk exposures, and pre-exposure prophylaxis (PrEP) is undergoing
      evaluation in clinical trials. Media reports have suggested substantial levels of
      community PrEP use despite its unproven effectiveness. METHODS: We conducted a
      cross-sectional survey of 1819 HIV-uninfected gay/bisexual men in California to
      assess PEP and PrEP awareness and use. RESULTS: Overall, 47% reported PEP
      awareness and 4% ever used PEP. Men who were older than 25 years of age (odds
      ratio [OR] = 2.2, 95% confidence interval [CI]: 1.5 to 3.1), were white (OR =
      2.2, 95% CI: 1.6 to 3.0), had an annual income >$100,000 (OR = 2.0, 95% CI: 1.2
      to 3.4), self-identified as gay/homosexual (OR = 2.4, 95% CI: 1.4 to 4.3), and
      had unprotected anal sex (OR = 1.8, 95% CI: 1.3 to 2.3) or sex under the
      influence of a drug (OR = 2.0, 95% CI: 1.5 to 2.7) were more likely to be aware
      of PEP, whereas speed users (OR = 0.6, 95% CI: 0.4 to 0.9) were less likely to be
      aware of PEP. Only 16% reported PrEP awareness, and <1% ever used PrEP.
      Unprotected anal sex (OR = 1.6, 95% CI: 1.1 to 2.3) and sex under the influence
      of a drug (OR = 1.5, 95% CI: 1.0 to 2.2) were associated with PrEP awareness.
      CONCLUSIONS: PEP awareness and use were modest and PrEP use was rare among
      gay/bisexual men in California. Although PrEP is not currently recommended,
      community education on the availability of PEP is suggested.

PMID- 18340658
TI  - Proceedings and abstracts of the 9th National Conference on Anticoagulant
      Therapy, May 3-5, 2007, Chicago, Illinois, USA.

PMID- 18340657
TI  - Low utilization of HIV testing during pregnancy: What are the barriers to HIV
      testing for women in rural India?
AB  - INTRODUCTION: Sixty percent of India's HIV cases occur in rural residents.
      Despite government policy to expand antenatal HIV screening and prevention of
      maternal-to-child transmission (PMTCT), little is known about HIV testing among
      rural women during pregnancy. METHODS: Between January and March 2006, a cross
      sectional sample of 400 recently pregnant women from rural Maharashtra was
      administered a questionnaire regarding HIV awareness, risk, and history of
      antenatal HIV testing. RESULTS: Thirteen women (3.3%) reported receiving
      antenatal HIV testing. Neither antenatal care utilization nor history of sexually
      transmitted infection (STI) symptoms influenced odds of receiving HIV testing.
      Women who did not receive HIV testing, compared with women who did, were 95% less
      likely to have received antenatal HIV counseling (odds ratio = 0.05, 95%
      confidence interval: 0.02 to 0.17) and 80% less aware of an existing HIV testing
      facility (odds ratio = 0.19, 95% confidence interval: 0.04 to 0.75). CONCLUSIONS:
      Despite measurable HIV prevalence, high antenatal care utilization, and STI
      symptom history, recently pregnant rural Indian women report low HIV testing.
      Barriers to HIV testing during pregnancy include lack of discussion by antenatal
      care providers and lack of awareness of existing testing services. Provider
      initiated HIV counseling and testing during pregnancy would optimize HIV
      prevention for women throughout rural India.

PMID- 18340659
TI  - Current awareness in phytochemical analysis.

PMID- 18340660
TI  - TP53 mutations in head and neck cancer.

PMID- 18340661
TI  - Cetuximab for colorectal cancer.

PMID- 18340662
TI  - Cetuximab for colorectal cancer.

PMID- 18340663
TI  - Cetuximab for colorectal cancer.

PMID- 18340664
TI  - Addition of insulin to oral therapy in type 2 diabetes.

PMID- 18340665
TI  - Retraction notice to " Activation of p38MAPK by repetitive low grade oxidative
      stress leads to pro-survival effects" [Biochim Biophys Acta Mol Cell Res 1773
      (2007) 367-374].

PMID- 18340666
TI  - Subgroup analyses in clinical trials.

PMID- 18340667
TI  - [Proceedings and abstracts of the 13th Session of the National College of
      Cardiologists of General Hospitals, Paris, France, 23-24 November 2007].

PMID- 18340668
TI  - Proceedings of the IETS Pre- and Post-Conference Symposia: Animal Models of
      Reproduction and Recent Developments in the Practice of Bovine Embryo Transfer,
      January 2008, Denver, Colorado, USA.

PMID- 18340669
TI  - Respiratory syncytial virus (RSV) vaccines--two steps back for one leap forward.
AB  - Respiratory viruses are among the most important causes of morbidity and
      mortality worldwide. From a vaccine viewpoint, such viruses may be divided into
      two principle groups-those where infection results in long-term immunity and
      whose continued survival requires constant mutation, and those where infection
      induces incomplete immunity and repeated infections are common, even with little
      or no mutation. Influenza virus and respiratory syncytial virus (RSV) typify the
      former and latter groups, respectively. Importantly, successful vaccines have
      been developed against influenza virus. However, this is not the case for RSV,
      despite many decades of research and several vaccine approaches. Similar to
      natural infection, the principle limitation of candidate RSV vaccines in humans
      is limited immunogenicity, characterised in part by short-term RSV-specific
      adaptive immunity. The specific reasons why natural RSV infection is
      insufficiently immunogenic in humans are unknown but circumvention of innate and
      adaptive immune responses are likely causes. Fundamental questions concerning
      RSV/host interactions remain to be addressed at both the innate and adaptive
      immune levels in humans in order to elucidate mechanisms of immune response
      circumvention. Taking the necessary steps back to generate such knowledge will
      provide the means to leap forward in our quest for a successful RSV vaccine.
      Recent developments relating to some of these questions are discussed.

PMID- 18340670
TI  - Emerging influenza.
AB  - In 1918 the Spanish influenza pandemic, caused by an avian H1N1 virus, resulted
      in over 50 million deaths worldwide. Several outbreaks of H7 influenza A viruses
      have resulted in human cases, including one fatal case. Since 1997, the outbreaks
      of highly pathogenic avian influenza (HPAI) of the H5N1 subtype have affected a
      wide variety of mammals in addition to poultry and wild birds. Here, we give an
      overview of the current knowledge of the determinants of pathogenicity of these
      three subtypes of avian influenza A virus in mammals. Common mechanisms for
      acquisition of virulence and replication of these avian influenza viruses in
      mammals are becoming apparent. Therefore, monitoring these and additional genetic
      changes upon zoonotic infections is important. Identification of genetic changes
      responsible for transmission between mammals will be an important task for the
      near future.

PMID- 18340671
TI  - Mimicking atrial parasystole.

PMID- 18340672
TI  - Re: Cardiac denervation does/does not play a major role in exercise limitation
      after heart transplantation.

PMID- 18340673
TI  - Re: Cardiac denervation does/does not play a major role in exercise limitation
      after heart transplantation.

PMID- 18340674
TI  - Re: Cardiac denervation does/does not play a major role in exercise limitation
      after heart transplantation.

PMID- 18340675
TI  - Re: Cardiac denervation does/does not play a major role in exercise limitation
      after heart transplantation.

PMID- 18340676
TI  - Re: Cardiac denervation does/does not play a major role in exercise limitation
      after heart transplantation.

PMID- 18340677
TI  - Improving outcomes through collaboration.
AB  - A roundtable was convened to examine the issues surrounding the use of hormonal
      therapy in the treatment of acne. Obstetrician-gynecologists (OB/ GYNs) and
      dermatologists often have varying views with regard to the use of oral
      contraceptives (OCs) and other agents in patients with acne. If polycystic ovary
      syndrome (PCOS), the most common hormonal cause of acne, has been diagnosed, the
      use of OCs is not usually disputed. Hormonal evaluation is recommended for
      certain conditions such as virilization. Although PCOS is often the source of the
      problem, it is important to rule out a testosterone-producing tumor or an adrenal
      tumor. It was determined, however, that the perception that OCs cause cervical
      and breast cancer persists among some dermatologists. Even in women with a family
      history of breast cancer, OCs do not increase the risk. Nor is cervical cancer
      related to OC use; rather, it results from human papillomavirus. Thus, patients
      should be assured that OCs will not increase their risk for either of these
      cancers. Female patients should be advised to see their gynecologists annually
      for breast and pelvic examinations and to discuss their concerns surrounding the
      use of OCs.

PMID- 18340678
TI  - [Hypertension : a quiet sign of danger in the dialysed patients].

PMID- 18340679
TI  - [Epidemiology of HTN in dialysis].
AB  - Increased cardio-vascular morbidity-mortality in dialysed patients is
      particularly due to an insufficiency of blood pressure control. Previous
      epidemiological surveys show that prevalence of dialysis hypertension is high,
      from 55 to 85% according to period and mean age of the studied population,
      despite an improvement of dialysis strategies during the last decade. Control of
      hypertension is not better in peritoneal dialysis than in haemodialysis.
      Antihypertensive drugs are administered to 3/4 of dialysed patients. Dialysis
      strategies which increase the number of sessions per week or the duration of each
      session in conventional haemodialysis improve the volume control and consequently
      the blood pressure. Atherosclerosis, cause or consequence of hypertension in
      dialysed elderly patients, more and more old, lead to adapt treatment strategies
      in order to prevent hypotension, which is also, a major risk factor of morbidity
      mortality in dialysed patients (reverse epidemiology).

PMID- 18340680
TI  - [The physiopathology of dialysis-associated hypertension].
AB  - Hypertension in subjects on long term dialysis is frequent. Its origins are found
      in extracellular volume overload, which is complicated by increased peripheral
      arterial resistance. The latter is affected by many systems, including that of
      renin-angiotensin, endothelin, nitric oxide, the sympathetic nervous system, and
      others. The interaction between these factors may explain why the control of
      hypertension in dialysis patients requires ongoing attention to the many aspects
      of good dialysis.

PMID- 18340681
TI  - [Arterial hypertension, chronic renal insufficiency and dialysis].
AB  - The principal characteristic of hypertension in chronic kidney disease (CKD),
      especially at CKD stage 5. Is an increased systolic pressure, with normal or even
      low diastolic pressure. This isolated systolic hypertension is also characterized
      by ab abnormal increase in pulse pressure which is by itself an independent
      cardiovascular risk factor. The principal reason for these abnormalities is
      accelerated ageing of arterial system, principally the aorta and large central
      arteries. This ageing is characterized by stiffening of arteritis whose natural
      history is not clearly understood. One of the principal pathogenic factor
      associated with stiffening is extensive calcification of arterial walls, mainly
      the medial layer (media-calcinosis). Mineral metabolism disorders such as
      hyperphosphatemia, play a major role in pathophysiology of calcifications.
      Arterial stiffness is characterized by very steep volume-pressure relationship
      and for this reason is associated with hemodynamic instability. Small blood
      volume increase producing abnormally high pressure while small decrease in blood
      volume could be associated with deep hypotension.

PMID- 18340682
TI  - [Does hypertension impact on the mortality of hemodialysis patients?].
AB  - Hypertension is very common in standard haemodialysis patients in spite of a wide
      use of antihypertensive medications. Up to the last decade it was reported in
      dialysis nts, as in the general population, as a powerful mortality risk factor.
      More recently several reports have challenged this view, and hypotension rather
      than hypertension has been claimed as the real culprit. That a risk factor has an
      opposite effect on mortality in conditions such as dialysis than in the general
      population has been termed - reverse epidemiology ,,, and suggests that our
      therapeutic approach toward blood pressure control in dialysis should be
      reconsidered. In fact, this counter intuitive concept is explained by the effect
      of time. Hypertension is a long-term mortality risk factor, that in a population
      crippled by short-acting risk factors (e.g. diabetes, congestive heart failure,
      malnutrition...) has not the opportunity to express itself. The clear cut noxious
      effect of hypertension on mortality in the years when dialysis patients were
      young and fit has disappeared in the present aged and highly co-morbid
      population. This does not mean that hypertension becomes beneficial once dialysis
      has been started. Hypotension is a marker of a high risk of early mortality,
      hypertension is a cause of late mortality. There is no evidence that hypertension
      might be protective in dialysis patients. Avoiding hypertension remains a capital
      goal of maintenance dialysis.

PMID- 18340683
TI  - [Fluid and sodium balance and blood pressure control in APD/CAPD].
AB  - Cardiovascular disease remains the leading cause of death in ESRD patients
      related to long-standing hypertension. Early studies had recognized the
      favourable effect of PD in controlling hypertension but it was soon realized that
      such benefit was not sustained. A U shaped trend of hypertension in patients on
      PD has been recently demonstrated as a result of a steadily increased blood
      pressure partly attributed to fluid retention resulting from lower sodium removal
      with time. Effort in selecting the best strategy of ultrafiltration for a single
      patient along with a careful and frequent monitoring of combined 24 hours sodium
      elimination coupled with dietician counseling can improve significantly fluid an
      sodium balance which in turn will result in much better blood pressure control.
      The contribution of progress in biocompatibility of PD fluid that better preserve
      renal function and the implementation of the first glucose polymer Icodextrin
      were key interventions in that aim. Further studies should be conducted to assess
      the power of innovative PD solutions--Low Sodium PDF and/or Bimodal
      Ultrafiltration--in enhancing fluid and sodium removal during CAPD/APD
      programmes.

PMID- 18340684
TI  - [Non-pharmacologic treatment of arterial hypertension in hemodialysis patients].
AB  - High blood pressure in dialysis patients is related to extracellular volume
      excess and the related increase of systemic vascular resistances. Scribner has
      early described the treatment of hypertension with ultrafiltration and low salt
      diet, without any drugs. The dry weight method relies on the progressive
      reduction of the postdialysis body weight until blood pressure is normalized.
      Additional measures are needed such as low salt diet, neutral sodium balance
      during dialysis treatment, stop of antihypertensive drugs, adequate length of the
      dialysis session, and patient education. It may exist a lag time between the
      normalization of the extracellular volume and blood pressure. It is related to
      the correction of the hemodynamic consequences of the extracellular volume
      overload. Moreover, the dry weight may potentially vary in patients undergoing
      catabolic intercurrent events. The complications of these changes (severe
      hypertension, pulmonary oedema) must be anticipated by the nephrologist and the
      staff to avoid additional morbidity to the patient.

PMID- 18340685
TI  - [Drug treatment of hypertension in hemodialysed patients].
AB  - A fraction of the dialyzed patients remains hypertensive despite achievement of
      the "dry weight" and will eventually require a pharmacological antihypertensive
      treatment. There is only scarce randomized intervention trials available in those
      patients so it is difficult to estimate whether the cardiovascular benefit of the
      treatment is related to blood pressure lowering per se or to class or drug
      specific properties. This paper reviews the different class of antihypertensive
      drugs focusing on their advantages and disadvantages in dialysis patients. On a
      practical ground, prescription will be driven by pharmacokinetics considerations
      and mostly according to specific indications pertinent to cardiovascular
      complications associated with hypertension.

PMID- 18340686
TI  - 'Short on solutions' N.J. report mostly offers analysis of what's wrong.

PMID- 18340687
TI  - Ohio readies charity standards. Effort comes in wake of new Form 990 from IRS.

PMID- 18340688
TI  - Tough choices ahead. Candidates ignore pain of needed cuts to health costs.

PMID- 18340689
TI  - ACHE Gold Medal Award. Administrator and mentor.

PMID- 18340690
TI  - ACHE Lifetime Award. Long record of service.

PMID- 18340691
TI  - Power struggle. Energy consumption, while not a top-tier concern for hospitals,
      has gained attention as execs look at economics of conservation.

PMID- 18340692
TI  - American Psychiatric Association practice guideline for the treatment of patients
      with Alzheimer's disease and other dementias. Second edition.

PMID- 18340693
TI  - Luke, the Physician (Harnack), With Remarks on the Literary, Dramatic and Medical
      Quality of the Third Gospel, and The Acts.

PMID- 18340694
TI  - An Account of the Festival Held at Stockholm, May, 1907, in Commemoration of the
      200th Anniversary of the Birth of Carolus Linnaeus.

PMID- 18340695
TI  - Tuberculosis and the Creative Mind.

PMID- 18340696
TI  - Physicians as Contributors to British and American Literature.

PMID- 18340697
TI  - The Medical Library and Its Contents.

PMID- 18340698
TI  - St. Louis Medical History Club.

PMID- 18340699
TI  - "The AESculapian.".

PMID- 18340700
TI  - The Reprinting of American Medical Classics.

PMID- 18340701
TI  - Geography and Medicine.

PMID- 18340702
TI  - Physicians as Contributors to British and American Literature.

PMID- 18340703
TI  - The Bookstall.

PMID- 18340704
TI  - St. Louis Medical History Club.

PMID- 18340705
TI  - Reprints of Medical Classics.

PMID- 18340706
TI  - Queries, Answers, and Appeals to Readers.

PMID- 18340707
TI  - The Writings of Benjamin Franklin Pertaining to Medicine and the Medical
      Profession.

PMID- 18340708
TI  - Irving Collins Rosse: A Biographical Sketch.

PMID- 18340710
TI  - Frere Jacques.

PMID- 18340709
TI  - A Reply to Dr. Walsh's "The Supposed Warfare Between Medical Science and
      Theology.".

PMID- 18340712
TI  - The Writings of Benjamin Franklin Pertaining to Medicine and The Medical
      Profession.

PMID- 18340711
TI  - Dr. Adam Thomson, Originator of the American Method of Inoculation for Small-Pox:
      An Historical Sketch.

PMID- 18340713
TI  - On Finding Books.

PMID- 18340714
TI  - A Reply to Dr. Walsh's "The Supposed Warfare Between Medical Science and
      Theology.".

PMID- 18340715
TI  - St. Louis Medical History Club.

PMID- 18340716
TI  - A Literary Controversy.

PMID- 18340717
TI  - Proceedings of the Fourth Annual Meeting.

PMID- 18340718
TI  - Report of Treasurer.

PMID- 18340719
TI  - Report of Manager of the Exchange.

PMID- 18340720
TI  - The Exchange.

PMID- 18340722
TI  - Library Items.

PMID- 18340721
TI  - A Visit to the Hunterian Library at Glasgow.

PMID- 18340723
TI  - Some Statistics from the Library of the New York Academy of Medicine.

PMID- 18340724
TI  - Annual Meeting, 1902.

PMID- 18340725
TI  - Lists for the Exchange.

PMID- 18340726
TI  - Question Box.

PMID- 18340727
TI  - Constitution.

PMID- 18340728
TI  - Libraries Represented.

PMID- 18340729
TI  - Proceedings of the Fifth Annual Meeting.

PMID- 18340730
TI  - Treasurer's Report.

PMID- 18340731
TI  - Report of Manager of the Exchange.

PMID- 18340732
TI  - Some Aspects of American Medical Bibliography: Address at the Meeting of the
      Association of Medical Librarians, Saratoga, June 10, 1902.

PMID- 18340733
TI  - Notes on the Bulletin Work of One Library: Address at the Meeting of the
      Association of Medical Librarians, Saratoga, June 10, 1902.

PMID- 18340734
TI  - Practical Hints on Bookbinding for Medical Libraries.

PMID- 18340736
TI  - Classification used at the Library of the College of Physicians, Philadelphia.

PMID- 18340735
TI  - Library of the College of Physicians, Philadelphia.

PMID- 18340737
TI  - Statistics of Medical Libraries.

PMID- 18340738
TI  - Instruction for Making the Union Catalogue of Medical Books, etc.

PMID- 18340739
TI  - Sketches of Medical Libraries: I. The Quine Library.

PMID- 18340740
TI  - The Work of an Association of Medical Librarians.

PMID- 18340741
TI  - The Medical Profession as Seen by Charles Dickens.

PMID- 18340743
TI  - Sketches of Medical Libraries: IV. The Library of the Pennsylvania Hospital, the
      Oldest Medical Library in America.

PMID- 18340742
TI  - The Colorado Medical Library Association.

PMID- 18340744
TI  - Sketches of Medical Libraries: III. The Worcester District Medical Library.

PMID- 18340746
TI  - Reprints - Their Origin or Destiny.

PMID- 18340745
TI  - The Physician in Fiction: II. The Medical Profession as Seen by William Makepeace
      Thackeray.

PMID- 18340747
TI  - Sketches of Medical Libraries: V. The Treadwell Library of the Massachusetts
      General Hospital.

PMID- 18340748
TI  - The Medical College Library.

PMID- 18340749
TI  - The Newberry Library.

PMID- 18340751
TI  - The Cincinnati Hospital Medical Library.

PMID- 18340750
TI  - Sketches of Medical Libraries: VII. The McGill Medical Library Montreal, Canada.

PMID- 18340752
TI  - The Library of the Imperial Institute of Experimental Medicine.

PMID- 18340753
TI  - The Library of the Odessa Jewish Hospital.

PMID- 18340754
TI  - The Library Laboratory in Medical Colleges.

PMID- 18340756
TI  - The Care of Pamphlets.

PMID- 18340755
TI  - Medical Libraries Proper, or Medical Departments in General Libraries.-Which?

PMID- 18340757
TI  - The Best Binding for Books-What to Use and What Not to Use.

PMID- 18340758
TI  - The Library of the Hahnemann Medical College of Philadelphia.

PMID- 18340759
TI  - The Library of the Society of Russian Physicians in the City of Riga, Russia.

PMID- 18340760
TI  - The Library of the Manchester Medical Society, Manchester, England.

PMID- 18340761
TI  - Report of Dr. Henry Sewall, Secretary of the Colorado Medical Library Association
      for the Year 1899.

PMID- 18340762
TI  - The Medical Profession as seen by George Eliot.

PMID- 18340764
TI  - The Lloyd Museum and Library, Cincinnati, O.

PMID- 18340763
TI  - A Working Library on Ophthalmology.

PMID- 18340765
TI  - Medical Department's in State Libraries.

PMID- 18340766
TI  - Sketches of Medical Libraries: XV. Medical Department of the Indianapolis Public
      Library.

PMID- 18340767
TI  - Prospectus.

PMID- 18340768
TI  - Dr. William Browning, Ph. B., M. D., Librarian of the Medical Society of the
      County of Kings.

PMID- 18340769
TI  - The Library of the Rhode Island Medical Society.

PMID- 18340770
TI  - The Need of a Medical Library.

PMID- 18340771
TI  - James R. Chadwick, M. D.

PMID- 18340772
TI  - A Working Library in Surgery.

PMID- 18340773
TI  - The Neglect of a Great Opportunity for the Advancement of Medicine and Surgery in
      Denver.

PMID- 18340774
TI  - Qualifications of a Medical Librarian: An Illustrative Case.

PMID- 18340775
TI  - The Medical College Library.

PMID- 18340776
TI  - How to Use a Medical Library.

PMID- 18340777
TI  - Medical Departments in Public Libraries-A Symposium.

PMID- 18340779
TI  - Melvil Dewey.

PMID- 18340778
TI  - Reprints-Suggestions to Medical Writers.

PMID- 18340780
TI  - Medical Departments in Rate Supported Public Libraries.

PMID- 18340781
TI  - Medical Departments in Public Libraries.

PMID- 18340782
TI  - Medical Departments in Public Libraries.

PMID- 18340783
TI  - Jacobus Berengarius Carpensi and his Commentaries on Mundinus.

PMID- 18340784
TI  - The Book-Worm.

PMID- 18340785
TI  - A Brief Account of the Library of the Medical Society of the County of Kings.

PMID- 18340786
TI  - A Few Hints on Medical Library Administration.

PMID- 18340787
TI  - A Practical System of Classification for Medical Libraries, Large or Small.

PMID- 18340788
TI  - Association of Medical Librarians.

PMID- 18340789
TI  - Johns Hopkins Hospital Historical Club.

PMID- 18340790
TI  - Editorial.

PMID- 18340791
TI  - The Medicine and Doctors of Juvenal.

PMID- 18340792
TI  - Memorial Address on the Late Samuel Smith Purple, M.D.

PMID- 18340793
TI  - A Brief Account of the Pennsylvania Infirmary for Diseases of the Eye and Ear,
      Established in the City of Philadelphia in the Year 1822.

PMID- 18340794
TI  - Remarks on Library Management.

PMID- 18340796
TI  - Dusting the Library.

PMID- 18340795
TI  - The Boston Medical Library.

PMID- 18340797
TI  - Editorial.

PMID- 18340798
TI  - In Lighter Vein.

PMID- 18340799
TI  - The Author of "Rab and His Friends," Dr. John Brown, of Edinburgh.

PMID- 18340800
TI  - A Review of the London Pharmacopoeia and Dispensatory of 1654 and a Brief
      Retrospect of the Period.

PMID- 18340801
TI  - Dr. John Richmond of East Hampton Parish: An Episode of an Old-Time Practitioner.

PMID- 18340802
TI  - A Sketch of the History of the Treatment of Chlorosis with Iron.

PMID- 18340803
TI  - Dr. Thomas Cadwalader's "Essay": A Hunt for an Historical Error.

PMID- 18340804
TI  - The Theories of Life Before the Hippocratic Era.

PMID- 18340805
TI  - The Typewriter in Cataloging and Shelf-Listing.

PMID- 18340806
TI  - Keeping Track of "Wants" and "Duplicates.".

PMID- 18340807
TI  - Association of Medical Librarians.

PMID- 18340809
TI  - Editorial.

PMID- 18340808
TI  - Historical Club of the Department of Medicine of the University of Pennsylvania.

PMID- 18340810
TI  - An Epitome of the History of Carcinoma.

PMID- 18340811
TI  - Modern Literary Pessimism from a Medical Standpoint.

PMID- 18340812
TI  - Founders of Modern Medicine.I. Thomas Willis,M.A., M.D.(A.D. 1621-1675).

PMID- 18340813
TI  - Founders of Modern Medicine: Giovanni Battista Morgagni. (1682-1771).

PMID- 18340814
TI  - A Brief Sketch of the Historical Club of the Department of Medicine of the
      University of Pennsylvania.

PMID- 18340816
TI  - Editorial.

PMID- 18340815
TI  - Completing Periodical Files and the Use of Card Check Lists.

PMID- 18340817
TI  - The Popes and the History of Anatomy.

PMID- 18340818
TI  - Founders of Modern Medicine. III: James Benignus Winslow. (A.D. 1669-1760.) With
      A Note on Theophilus Bonetus and the "Sepulchretum.".

PMID- 18340819
TI  - Medicine in Its Relation to Human Progress.

PMID- 18340820
TI  - Titles of Books and Miscellaneous Documents.

PMID- 18340821
TI  - A Brief History of the Library of the Physicians to the German Hospital and
      Dispensary of the City of New York.

PMID- 18340822
TI  - Presentation of the Library of the Physicians to the German Hospital and
      Dispensary of the City of New York to the Library of the Medical Society of the
      County of Kings.

PMID- 18340823
TI  - Johns Hopkins Hospital Historical Club.

PMID- 18340824
TI  - Historical Club of the Department of Medicine of the University of Pennsylvania.

PMID- 18340826
TI  - Resume of Current Literature.

PMID- 18340825
TI  - Editorial.

PMID- 18340827
TI  - The Origin of Louisiana Leprosy: A Preliminary Note.

PMID- 18340828
TI  - The "Phthisiologia" of Richard Morton, M.D.

PMID- 18340829
TI  - Extracts from the Journal of a Scotch Medical Student of the Eighteenth Century.

PMID- 18340830
TI  - A Sketch of John Abernethy.

PMID- 18340831
TI  - The Medical Library Movement in the United States.

PMID- 18340832
TI  - Association of Medical Librarians.

PMID- 18340834
TI  - Editorial.

PMID- 18340833
TI  - Historical Club of the Department of Medicine of the University of Pennsylvania.

PMID- 18340835
TI  - Our Obstetrical and Gynecological Ancestors.

PMID- 18340836
TI  - Autobiographical Account of a Case of Suspended Animation in the Eighteenth
      Century.

PMID- 18340837
TI  - A Letter "Explaining the Difference between Christian Science and Some Other
      Systems".

PMID- 18340838
TI  - Winslow as Viewed by a Contemporary.

PMID- 18340839
TI  - The University of the State of Pennsylvania.

PMID- 18340840
TI  - An Historical Sketch of the American Medical Association.

PMID- 18340841
TI  - The Reverend Gershom Bulkeley of Connecticut, an Eminent Clerical Physician.

PMID- 18340842
TI  - Professor of Medicine, University of Edinburgh, 1747-1766.

PMID- 18340843
TI  - The History of Tuberculous Meningitis.

PMID- 18340844
TI  - Nicholas Steno.

PMID- 18340845
TI  - The Medical Library as a Factor in Medical Education.

PMID- 18340846
TI  - Medical Libraries in Smaller Cities.

PMID- 18340847
TI  - Medical Libraries, Medical Publishers and the Medical Profession.

PMID- 18340848
TI  - The New York State Medical Library.

PMID- 18340849
TI  - A Brief History of the Rush Monument.

PMID- 18340851
TI  - Johns Hopkins Hospital Historical Club.

PMID- 18340850
TI  - Association of Medical Librarians.

PMID- 18340853
TI  - The Development of Animal Physiology.

PMID- 18340852
TI  - Editorial.

PMID- 18340854
TI  - Samuel Sharp, the First Surgeon to make the Corneal Incision in Cataract
      Extraction with a Single Knife: A Biographical and Historical Sketch.

PMID- 18340856
TI  - From Hippocrates to Galen.

PMID- 18340855
TI  - The Importance of the Study of the History of Medicine.

PMID- 18340857
TI  - The Phenomenism of Hippocrates.

PMID- 18340859
TI  - Association of Medical Librarians.

PMID- 18340858
TI  - Editorial.

PMID- 18340861
TI  - Copernicus: Physician, Clergyman and Astronomer.

PMID- 18340860
TI  - The Medical Side of Rabelais.

PMID- 18340863
TI  - Joseph Towne, Wax Modeller of Guy's Hospital.

PMID- 18340864
TI  - Medical Libraries.

PMID- 18340865
TI  - The Development of Animal Physiology: The Physiology of Aristotle.

PMID- 18340866
TI  - Historical Club of the Department of Medicine of the University of Pennsylvania.

PMID- 18340867
TI  - Editorial.

PMID- 18340868
TI  - Association of Medical Librarians.

PMID- 18340869
TI  - Proposed Regulation of the Practice of Medicine and Surgery in Pennsylvania in
      the Eighteenth Century.

PMID- 18340870
TI  - Voltaire on Syphilis.

PMID- 18340872
TI  - The Development of Animal Physiology: Some of the Teachings of Aristotle
      Concerning the Generation of Animals.

PMID- 18340871
TI  - The Need Of a Medical Library In Buffalo.

PMID- 18340873
TI  - Historical Section of the Buffalo Medical Journal Club.

PMID- 18340874
TI  - A Portrayer of Kings-and Doctors.

PMID- 18340875
TI  - Dr. Johann David Schoepf, Surgeon of the Anspach-Bayreuth Troops in America, 1777
      1784.

PMID- 18340876
TI  - The Medical Library of the University of Michigan.

PMID- 18340877
TI  - Superstition in Medicine.

PMID- 18340878
TI  - Some Relations of the Church and Scientific Progress: An Introductory Address.

PMID- 18340879
TI  - The Development of Animal Physiology: The Theory of Animal Generation According
      to Aristotle.

PMID- 18340880
TI  - Value of a Medical Library to the Community.

PMID- 18340881
TI  - Historical Section of the Buffalo Medical Journal Club.

PMID- 18340882
TI  - Editorial.

PMID- 18340883
TI  - Is There a Medical Counterpart to the Kulturgeschichte Controversy?

PMID- 18340884
TI  - Dr. Robert Child, and His Troubles with the Puritan Fathers.

PMID- 18340885
TI  - European Medicine: A Resume of Medical Progress During the Eighteenth and
      Nineteenth Centuries.

PMID- 18340886
TI  - Pope John XXII and the Supposed Bull Forbidding Chemistry.

PMID- 18340887
TI  - The Bibliography of the Religio Medici of sir Thomas Browne.

PMID- 18340888
TI  - The Development of Animal Physiology: Some of the Physiologic Teachings of
      Praxagoras of Cos.

PMID- 18340889
TI  - Medical Libraries in Hospitals.

PMID- 18340890
TI  - Method of Keeping Case Records for Small Hospitals.

PMID- 18340891
TI  - Editorial.

PMID- 18340893
TI  - Exception Taken to the Publication of Dr. Cruikshankis Article.

PMID- 18340892
TI  - Exception Taken to the Publication of Dr. Cruikshankis Article.

PMID- 18340894
TI  - Exception Taken to the Publication of Dr. Cruikshankis Article.

PMID- 18340895
TI  - Exception Taken to the Publication of Dr. Cruikshankis Article.

PMID- 18340896
TI  - The Graduation Ceremony; With an Account of Some Modern Surgical Celebrations.

PMID- 18340898
TI  - Some Points in the Interior Arrangement and Construction of a Building for a
      Special Library.

PMID- 18340897
TI  - The Development of Animal Physiology: Some Physiologic Concepts of Theophrastus.

PMID- 18340899
TI  - A Tribute to the Memory of Dr. James Read Chadwick: Excerpted from the Thirtieth
      Annual Report of the Boston Medical Library.

PMID- 18340900
TI  - Association of Medical Librarians.

PMID- 18340901
TI  - St. Louis Medical History Club.

PMID- 18340902
TI  - Editorial.

PMID- 18340903
TI  - A Sketch of the Life of Thomas Bond, Clinician and Surgeon.

PMID- 18340904
TI  - The Alleged Dedication of Morgagni Recognizing Kinship to John Morgan.

PMID- 18340905
TI  - A Biography of Francois Magendie.

PMID- 18340906
TI  - The Antagonism of the Church to Scientific Progress During the Middle Ages: The
      Facts of the Case, and a Reply to the Criticism of Dr. James J. Walsh.

PMID- 18340907
TI  - The Antagonism of the Church to Scientific Progress During the Middle Ages: The
      Facts of the Case, and a Reply to the Criticism of Dr. James J. Walsh.

PMID- 18340908
TI  - European Medicine: A Resume of Medical Progress During the Eighteenth and
      Nineteenth Centuries.

PMID- 18340909
TI  - The Dutch Physician in New Amsterdam and His Colleagues at Home.

PMID- 18340911
TI  - A Photograph of the Head of Cardinal Richelieu Taken Two Hundred and Fifty Years
      After Death.

PMID- 18340910
TI  - The Trend of Medical Practice.

PMID- 18340912
TI  - Experiences of an American Physician at the Captuure of Washington by the British
      in 1814.

PMID- 18340913
TI  - On Union in Medicine: With Some Reflections on the Present State of Homeopathy
      and Homeopathic Literature.

PMID- 18340914
TI  - A Biography of Francois Magendie.

PMID- 18340915
TI  - The Development of Animal Physiology: Notes on Some Early Peripatetics and
      Praxagoreans.

PMID- 18340917
TI  - Johns Hopkins Hospital Historical Club.

PMID- 18340916
TI  - A Sketch of the Library of the Surgeon-General's Office.

PMID- 18340919
TI  - Editorial.

PMID- 18340918
TI  - St. Louis Medical History Club.

PMID- 18340921
TI  - A Sketch of Benjamin Rush.

PMID- 18340920
TI  - The Hotel-Dieu of Paris: An Historical Sketch.

PMID- 18340922
TI  - A Forgotten Medical Worthy, Dr. Diego Alvarex Chanca, of Seville, Spain, and His
      Letter Describing the Second Voyage of Christopher Columbus to America.

PMID- 18340923
TI  - The Supposed Warfare Between Medical Science and Theology.

PMID- 18340924
TI  - Controversy (A Quatrain.).

PMID- 18340925
TI  - German-American Influence in Medicine and Surgery.

PMID- 18340927
TI  - Editorial.

PMID- 18340926
TI  - A Biography of Francois Magendie.

PMID- 18340929
TI  - Some Lessons from the Life of Major Walter Reed.

PMID- 18340928
TI  - The Mondino Myth.

PMID- 18340930
TI  - Leonardo da Vinci and Vesalius: A Review.

PMID- 18340931
TI  - Joseph Roby, the Anatomist.

PMID- 18340932
TI  - A Biography of Francois Magendie.

PMID- 18340933
TI  - Historical Club of the Department of Medicine of the University of Pennsylvania.

PMID- 18340934
TI  - St. Louis Medical History Club.

PMID- 18340935
TI  - Editorial.

PMID- 18340936
TI  - Biographical Cyclopedia of Medical Men.

PMID- 18340937
TI  - Charles White: Surgeon and Obstetrician.

PMID- 18340939
TI  - A Biography of Francois Magendie.

PMID- 18340938
TI  - Aelius Aristides, A Hypochondriac in the Time of the Antonines.

PMID- 18340940
TI  - Should the Size or Growth of a Medical Library be Restricted.

PMID- 18340941
TI  - Association of Medical Librarians.

PMID- 18340943
TI  - Editorial.

PMID- 18340942
TI  - Association of Medical Librarians.

PMID- 18340944
TI  - How Much is the Library Appreciated.

PMID- 18340946
TI  - Association of Medical Librarians.

PMID- 18340945
TI  - The Association of Medical Librarians; Past, Present and Future.

PMID- 18340947
TI  - St. Louis Medical History Club.

PMID- 18340948
TI  - Editorial.

PMID- 18340949
TI  - Doctors of Samuel Johnson and His Court.

PMID- 18340951
TI  - Early Medical Libraries in America; Being an Account of the Origin and Growth of
      the Libraries of the Pennsylvania Hospital and of the College of Physicians of
      Philadelphia.

PMID- 18340950
TI  - Pasteur, A Study and Appreciation of his Career from a Layman's Standpoint.

PMID- 18340952
TI  - A Brief History of Antiseptic Surgery.

PMID- 18340953
TI  - Charles Linnaeas, M.D.

PMID- 18340954
TI  - Linnaeus' "Genera Morborum," and Some of His Other Medical Works.

PMID- 18340956
TI  - Medical Departments in Public Libraries.

PMID- 18340955
TI  - Doctors of Samuel Johnson and His Court.

PMID- 18340958
TI  - Tuberculosis and the Creative Mind.

PMID- 18340957
TI  - Editorial.

PMID- 18340959
TI  - The History of Mole Pregnancy.

PMID- 18340960
TI  - Doctors of Samuel Johnson and His Court.

PMID- 18340961
TI  - Diseases of Great Physicians of the Past.

PMID- 18340963
TI  - St. Louis Medical History Club.

PMID- 18340962
TI  - Medical History Repositories: A Suggestion.

PMID- 18340964
TI  - Editorial.

PMID- 18340965
TI  - Article withdrawal notice.

PMID- 18340966
TI  - Progress towards reducing   measles mortality and   eliminating measles, WHO  
      Eastern Mediterranean   Region, 1997-2007.

PMID- 18340967
TI  - Werner J. Schmidt (1950-2007). Pushing the boundary of neuroscience: a true
      academician and a complete gentleman.

PMID- 18340968
TI  - [Psychiatry as a therapeutic discipline].

PMID- 18340969
TI  - Themes in World Health.

PMID- 18340970
TI  - Senses of belonging: the politics of working-class insurance in Britain, 1880
      1914.

PMID- 18340971
TI  - Genomic 'valleys of death'.

PMID- 18340972
TI  - Data page. Number of hospital beds rise, community hospitals drop.

PMID- 18340973
TI  - [Insect proteins transporting hydrophobic substances: Introduction].

PMID- 18340974
TI  - Kangaroo mother care.

PMID- 18340975
TI  - Role of nurse in beating heart bypass surgery.

PMID- 18340976
TI  - Hot fomentation versus cold compress for reducing intravenous infiltration.

PMID- 18340977
TI  - Dental adhesives .... how it all started and later evolved.
AB  - This article describes how dental adhesives evolved from the cements developed by
      the Mayan Indians into today's modern dental adhesives. Particular attention is
      paid to Oskar Hagger, a chemist who worked for DeTrey/Amalgamated Dental Company,
      and already in 1949 developed an adhesive product called Sevriton Cavity Seal.
      That adhesive was acidic and interacted with the tooth surface on a molecular
      level. His ground-breaking concept makes him the true "Father of Modern Dental
      Adhesives." Hagger's concept was soon adopted by other investigators, and
      different generations of dental adhesives evolved thereafter. Today, after many
      years of accepting that the key to the success of dental adhesives is the
      micromechanical retention resulting from acid etching of dentin and enamel, we
      still return to Dr. Hagger's original concept that bonding can be achieved via
      molecular interactions between adhesives and tooth surfaces. That concept is
      obvious in the development of newer generations of dentin adhesives. These
      adhesives, like Sevriton Cavity Seal, rely on acidic monomers capable of etching
      and interacting on a molecular level with tooth surfaces in order to form
      physical/chemical bonds between the restoration and the tooth. Whether Hagger's
      concept will become the norm in the future is still an open question, but one
      thing is certain: Hagger's idea is still very much alive.

PMID- 18340978
TI  - Effectiveness of all-in-one adhesive systems tested by thermocycling following
      short and long-term water storage.
AB  - PURPOSE: To evaluate and compare the marginal integrity of in vitro Class V
      restorations made with all-in-one adhesive systems by thermocycling after
      different periods of water storage, to provide an analysis of static and quasi
      dynamic deterioration in water. MATERIALS AND METHODS: Standardized Class V
      cavities (17 groups, 8 specimens each) were prepared in extracted human caries
      free anterior teeth. The cavities were filled using 14 all-in-one adhesive
      systems/composite resin combinations in addition to the multi-bottle adhesive
      systems Syntac and OptiBond FL (etch-and-rinse technique) and Clearfil SE Bond
      (self-etching) as controls. The samples were thermocycled after water storage for
      21 days, after 1 year and again after 3 years (2000 cycles between 5 and 55
      degrees C) and replicas were made before and after each thermocycling treatment
      (TC) for quantitative marginal analysis in the SEM. RESULTS: In dentin, marginal
      adaptation showed no significant differences between all groups after the first
      TC. After one year of water storage and a second TC, the results for Prompt L-Pop
      (1999), Adper Prompt L-Pop/Tetric Ceram, and One-up Bond F Plus showed a
      statistically significant decrease of margin quality 1 (MQ1) score compared to
      the reference groups. When the all-in-one adhesives G-Bond, AQ-Bond, Hybrid Bond,
      and One-up Bond F Plus were used, the enamel margins of restorations showed lower
      percentages of "continuous margins" (p < 0.05) after 1 year of water storage and
      TC. Of the materials tested after 3 years of water storage and TC, only AQ Bond
      had a significantly lower MQ1 score. CONCLUSION: While all materials exhibited
      deterioration in the MQ1 quality score, the rate of deterioration varied, and the
      results show that different materials have different deterioration rates after
      initial vs long-term water storage. The deterioration along margins in dentin was
      not as extensive as predicted from other studies; however, the results from the
      enamel margins show that one-bottle all-in-one adhesives seem to be significantly
      affected by water storage. The results of this study suggest that the all-in-one
      adhesive group members perform very differently from each other: thus, data need
      to be explored further at the level of each different adhesive product.

PMID- 18340979
TI  - Clinical bonding of a single-step self-etching adhesive in noncarious cervical
      lesions.
AB  - PURPOSE: The aim of this study was to evaluate the clinical retention to dentin
      of a single-step self-etching adhesive system. MATERIALS AND METHODS: A total of
      133 Class V restorations were placed with the self-etching primer Xeno III and a
      resin composite (Tetric Ceram) or a polyacid-modified resin composite (Dyract AP)
      in noncarious cervical lesions without intentional enamel involvement. The
      restorations were evaluated at baseline and then every 6 months during a 2-year
      follow-up. Dentin bonding efficacy was determined by the percentage of lost
      restorations. RESULTS: During the 2 years, 130 restorations could be evaluated.
      The cumulative loss rate at 2 years was 7.7%, with no significant differences
      between the two restorative materials. The self-etching adhesive fulfilled the 18
      month full acceptance ADA criteria. CONCLUSION: The single-step self-etching
      adhesive showed acceptable clinical retention rates to dentin surfaces during the
      evaluation period independent of restorative material used.

PMID- 18340980
TI  - Shear bond strength and physicochemical interactions of XP Bond.
AB  - PURPOSE: The purpose of this study was to evaluate the shear bond strength of
      composite to dentin and enamel using the new etch-and-rinse adhesive XP Bond
      compared to other adhesives (OptiBond Solo Plus, Adper Scotchbond 1 XT, Syntac
      Classic). MATERIALS AND METHODS: Shear bond strength (MPa) was measured by
      shearing a resin cylinder 4.5 mm in diameter from prepared buccal surfaces of
      human third molars using an Instron Testing Machine equipped with a chisel-shaped
      rod. In addition, micro-Raman spectroscopy was performed to determine if there
      was a chemical interaction between the resin adhesive and dentin and enamel.
      RESULTS: Significant differences were observed among the dentin and enamel values
      generated with the adhesives tested. XP Bond generated statistically similar
      values to Optibond Solo Plus and Adper Scotchbond 1 XT to both enamel and dentin.
      Syntac Classic generated significantly lower values to both enamel and dentin.
      CONCLUSION: Micro-Raman spectroscopy showed a complete infiltration of resin into
      the demineralized dentin zone. In addition, it strongly suggested a chemical
      interaction with XP Bond and components of dentin. It is hypothesized that this
      interaction is due to the formation of calcium phosphate complexes derived from
      mineral apatite in the dentin and phosphate esters in the adhesive.

PMID- 18340981
TI  - Microshear fatigue testing of tooth/adhesive interfaces.
AB  - PURPOSE: The objective of the present study was to determine the fatigue
      resistance of several contemporary dentin adhesives as well as a resin-modified
      glass-ionomer cement. MATERIALS AND METHODS: Cyclic loading of the adhesive
      interface was achieved by a microshear fatigue setup following a staircase
      approach, where the stress level at which 50% of the specimens fail after 10(4)
      cycles was calculated as the median microshear fatigue resistance (muSFR).
      RESULTS: For all products tested, the muSFR was lower than the microshear
      strength. A wide spread in muSFR was observed, ranging from 24% to 76% of the
      quasi-static microshear strength, irrespective of the type of adhesive used.
      CONCLUSION: The results of this study show that the microshear test setup is a
      discriminative and reproducible way of testing tooth/adhesive interfaces, even at
      relatively low stresses. The results clearly indicate that such interfaces are
      vulnerable to progressive damage by cyclic loads. Further, at present there is
      not one bonding approach, whether "total etch" or "self-etching", that
      consistently yields higher fatigue resistance: the product factor seems to be of
      primary importance.

PMID- 18340982
TI  - Microleakage of Class V composite restorations placed with etch-and-rinse and
      self-etching adhesives before and after thermocycling.
AB  - PURPOSE: To evaluate the sealing ability of etch-and-rinse and self-etching
      adhesives in Class V cavities before and after thermocycling in vitro. MATERIALS
      AND METHODS: Etch-and-rinse adhesives (Prime & Bond NT [P&B], XP Bond [XPB],
      Scotchbond 1 XT [SBX], Syntac [SYN]) and self-etching adhesives (Xeno III [XNO],
      i-Bond [IBO], Clearfil SE Bond [CLF]) were used. A microleakage test was
      performed to evaluate marginal sealing. Seventy molars were divided into seven
      groups according to the adhesive used. Class V cavities were restored and each
      group was divided into two subgroups. One group was water immersed for 24 h and
      the other was thermocycled. Then, specimens were immersed in fuchsin and
      sectioned. Microleakage and dentin permeability were recorded on occlusal and
      gingival walls and data were statistically analyzed. RESULTS: Etch-and-rinse
      adhesives provided perfect occlusal sealing. Self-etching adhesives obtained
      slight occlusal leakage. In the gingival wall, XNO and CLF showed the lowest
      leakage, followed by XPB and SBX, then P&B. SYN and IBO exhibited the highest
      leakage. All SE adhesives and XPB provided sealed dentinal tubules. Thermocycling
      did not affect the occlusal sealing but reduced the gingival sealing when P&B,
      SYN, XNO, CLF, and IBO were used. CONCLUSION: In enamel, marginal leakage was
      prevented when phosphoric acid was used. Self-etching adhesives promoted slight
      occlusal leakage. The gingival sealing was poorer than the occlusal sealing. XNO,
      CLF followed by XPB obtained the best gingival sealing. Thermocycling did not
      affect the occlusal bonding but reduced the gingival sealing, except when XPB and
      SBX were used.

PMID- 18340983
TI  - Microleakage of XP Bond in Class II cavities after artificial aging.
AB  - PURPOSE: To determine the microleakage of etch and rinse adhesives. MATERIALS AND
      METHODS: Standardized Class II cavities were cut in 40 human molars with one
      proximal box limited within enamel and one proximal box extending into dentin.
      Teeth were assigned randomly to 5 groups (n = 8) and restored with incrementally
      placed composite restorations. Five combinations were tested: G1 = XP Bond +
      Ceram X Mono, G2 = Syntac Classic + Tetric EvoCeram, G3 = Scotchbond 1 XT + Z250,
      G4 = P&B NT + Ceram X mono, G5 = Optibond Solo Plus + CeramX Mono. After
      finishing and polishing, teeth were stored for 48 h in water at 37 degrees C
      before being subjected to artificial aging by thermal stress (5/55 degrees C,
      2000x, 30 s) and mechanical loading (50 N, 50,000x). Teeth were isolated with
      nail varnish and immersed in 5% methylene blue for 1 h. After sectioning,
      specimens were evaluated for leakage (ordinal scale: 0 to 4) at enamel and dentin
      margins under a stereomicroscope. Results were analyzed using the Kruskal-Wallis
      H-test and Mann-Whitney U-test (p < 0.05). RESULTS: Statistical analysis showed
      significant differences among the groups in both enamel and dentin. Mean ranks (H
      test) were: enamel: G2 (64.44) < G1 (66.69) < G4 (74.88) < G3 (98.25) and G5
      (98.25); dentin: G3 (65.53) < G1 (74.42) < G4 (81.09) < G2 (81.84) < G5 (99.61).
      CONCLUSION: Microleakage of XP Bond is at the same level as or even better than
      other etch-and-rinse adhesives.

PMID- 18340984
TI  - Six-month clinical evaluation of XP BOND in noncarious cervical lesions.
AB  - PURPOSE: To evaluate the 6-month clinical performance of the etch-and-rinse one
      bottle adhesive system XP BOND, used in combination with the composite resin
      Ceram X duo for the restoration of Class V noncarious cervical lesions (NCCL).
      MATERIALS AND METHODS: XP BOND was tested in a total of 40 patients who received
      two Class V Ceram X duo restorations, Adper Scotchbond 1 XT was used as a
      control. After cleaning the teeth, the surface of the NCCL was treated using a
      carbide bur in dentin and a 40-microm diamond bur in enamel with no retentive
      preparations. The lesions were filled with two increments of Ceram X duo after
      the application of the respective adhesive by a single operator according to
      manufacturer's instructions. After 6 months, the retention and the marginal
      integrity were evaluated. RESULTS: Thirty-eight of 40 patients were evaluated
      after 6 months by two clinicians according to modified USPHS criteria, and all
      restorations using XP BOND were still in place. In the control group (using Adper
      Scotchbond 1XT), one restoration was lost. The statistical evaluation (chi2 test)
      showed no significant differences in any of the criteria. No difference of
      marginal integrity was found between the two adhesive systems. CONCLUSION: XP
      BOND meets the ADA success criteria after 6 months.

PMID- 18340985
TI  - Adhesive luting revisited: influence of adhesive, temporary cement, cavity
      cleaning, and curing mode on internal dentin bond strength.
AB  - PURPOSE: To evaluate microtensile bond strength to Class I cavity floor dentin
      beneath adhesive inlays that were luted with different adhesives, temporary
      cements, cleaning methods, and curing modes. MATERIALS AND METHODS: Occlusal
      cavities (4 x 4 mm, depth 3 mm) were prepared in 96 extracted human third molars.
      One part of the cavities was temporized with different temporary cements, which
      were removed after one week using three techniques (scaler or air polishing with
      Prophypearls or ClinPro powder). Direct resin composite inlays (Clearfil AP-X)
      were then placed with the luting composite Calibra using three adhesives (XP
      BOND/SCA, Syntac, OptiBond FL). Teeth were cut into beams and after 24 h of water
      storage at 37 degrees C, the sticks were subjected to microtensile bond strength
      evaluation. Samples were subjected to SEM fractographic analysis of failed
      interfaces. RESULTS: Contamination with temporary cement reduced dentin bond
      strengths (p < 0.05). Removing remnants of cements with Prophypearls air
      polishing resulted in the lowest bond strengths (p < 0.05). Separate light curing
      of the adhesives did not produce higher dentin bond strengths (p > 0.05). Syntac
      still worked when Heliobond was omitted (p > 0.05). Immediate dentin sealing
      prior to temporizing increased internal bond strength (p < 0.05). CONCLUSION: The
      dual-cured adhesive provided higher internal bond strengths between adhesive
      inlays and dentin. Contamination of dentin with temporary cements is a hazard for
      excellent dentin adhesion of adhesive inlays. Therefore, immediate dentin sealing
      and resin coating is promising.

PMID- 18340986
TI  - XP BOND in self-curing mode used for luting porcelain restorations. Part A:
      Microtensile test.
AB  - PURPOSE: To assess the bond strength to dentin of an experimental adhesive and
      the proprietary resin cement used in different curing modes to lute ceramic disks
      of different thicknesses. MATERIALS AND METHODS: Empress II disks (Ivoclar
      Vivadent) were luted to dentin using XP BOND (Dentsply [XP]) in combination with
      the proprietary self-curing activator (SCA) and cement Calibra (Dentsply [C]).
      Curing of the adhesive was induced either by mixing with the activator
      (activator, groups 3 to 6) or by light irradiation for 20 s (group 2). The cement
      was either light cured for 40 s through the ceramic onlay (groups 1 to 5) or
      cured chemically (groups 6 and 7). Groups 2 and 4 were compared with group 1, in
      which Prime & Bond NT (Dentsply DeTrey) was tested as control. In groups 3 and 6,
      2-mm-thick onlays were luted with XP+SCA, and the cement was light cured for 40 s
      or autocured for 5 min, respectively. These groups were compared with group 7, in
      which Syntac (Ivoclar Vivadent) was applied with C and, in order to reproduce the
      handling procedures of group 6 (although contrary to manufacturer's
      instructions), no light irradiation was provided for the adhesive or the cement.
      The influence of onlay thickness (2, 3, 4 mm) on the bond strength developed by
      XP+SCA/C was assessed by comparing groups 3, 4, 5. In these groups, C was light
      cured for 40 s through the onlay. Microtensile beams were obtained from the luted
      teeth. RESULTS: Bond strengths not including pretest failures (in parentheses:
      value including pretest failures as 0 MPa) were 21.0 (17.5) MPa in group 1, 24.9
      (21.2) MPa in group 2, 23.7 (21.3) MPa in group 3, 29.9 (26.7) MPa in group 4,
      30.3 (24.6) MPa in group 5, 28.6 (24.6) MPa in group 6, and 17.1 (9.2) MPa in
      group 7. Statistically significant differences were found between groups 1 and 4,
      groups 3 and 5, and groups 6 and 7. CONCLUSION: The bonding potential of XP BOND
      used with the activator or light cured in combination with Calibra in self- or
      dual-curing mode outperformed that of a control adhesive-cement system. The bond
      strength of XP+ SCA + Calibra was not negatively affected by the onlay thickness.

PMID- 18340987
TI  - XP BOND in self-curing mode used for luting porcelain restorations. Part B:
      Placement and 6-month report.
AB  - PURPOSE: The aim of this clinical study was to evaluate the postoperative
      hypersensitivity of Empress II inlays/onlays luted under clinical conditions with
      XP BOND in combination with SCA and Calibra cured in self-curing mode. MATERIALS
      AND METHODS: Fifty-three restorations were placed in 38 patients in March and
      April 2006. No patient received more than two restorations. Luting procedures
      were performed following manufacturers' instructions. The restorations were
      evaluated after 2 weeks and 6 months for postoperative hypersensitivity, marginal
      discoloration, marginal integrity, secondary caries, maintenance of interproximal
      contact, and fracture. RESULTS: At the 2-week recall, the postoperative
      hypersensitivity was reported in only 10 and after 6 months in only 3 patients.
      All other parameters showed alpha scores. CONCLUSION: All the evaluated
      restorations were in place and acceptable. The postoperative hypersensitivity
      recorded after using XP BOND and Calibra in self-curing mode was clinically
      acceptable.

PMID- 18340988
TI  - [The pacemaker and automated implantable defibrillator in daily care].

PMID- 18340989
TI  - [Blood pressure in cardiac insufficiency, an educational mission].

PMID- 18340990
TI  - [Rehabilitation of the coronary patient, a diverse process].

PMID- 18340991
TI  - [The nurse at the home of the chronic stabilized coronary insufficiency patient].

PMID- 18340992
TI  - [The Nantes clinics in partnership with the Respecticoeur network].

PMID- 18340993
TI  - [The adaptation of coronary insufficiency patients to a low-salt diet].

PMID- 18340994
TI  - [Ablation of atrial fibrillation].

PMID- 18340995
TI  - [Recent understanding of sepsis: mechanisms of organ dysfunction and advances in
      treatment --preface and comments].
AB  - This special issue focuses on recent advances in understanding pathogenesis and
      altered physiology of sepsis on cellular and molecular basis. It is recognized
      that remarkable advances have been made in understanding the basic cellular and
      molecular mechanisms of multiple organ dysfunction associated with sepsis. The
      rationale for therapeutic targets in sepsis has arisen from the concept of
      pathogenesis. Although a lot of clinical trials have been conducted, a small
      number of treatment or management protocols have been proven to be effective in
      severe sepsis. Although critical questions remain unanswered, these new insights
      into sepsis-associated mechanisms are likely to lead to effective treatment
      approaches that ultimately improve clinical outcome.

PMID- 18340996
TI  - [Pathophysiology of sepsis--will the basic research contribute to the improvement
      of outcome in clinical sepsis?].
AB  - In this decade, the molecular mechanism of sepsis has been strikingly clarified.
      Especially, the identification of toll-like receptors as the pivotal molecules
      for the recognition of the stimulation of the inflammatory products of
      microorganisms has contributed to the elucidation of intracellular signaling
      pathways which result in severe systemic inflammatory response in sepsis. The
      production and release of a variety of pro-inflammatory mediators have been found
      to be associated with severe systemic inflammation and multiple organ dysfunction
      syndrome (MODS). In the pathophysiology of the development of MODS in sepsis, the
      disturbance of peripheral microcirculation, the insult of tissues and cells by
      leukocytes and activated complements and the augmentation of the disorder of
      fibrinolytic and coagulation systems, which often results in the outbreak of
      disseminated intravascular coagulopathy (DIC), will be critically involved.
      Despite of the advance in the basic research regarding molecular pathophysiology
      of sepsis, sepsis is still accompanied by high mortality in clinical settings.
      Almost all clinical trials targeting sepsis-associated mediators have failed,
      except the substitution therapy of activated protein C. However, further trials
      based on the basic findings, including the therapies targeting the multiple
      mediators, will contribute to the improvement of outcome of clinical sepsis. ple
      organ dysfunction syndrome (MODS), pro-inflammatory mediator, disseminated
      intravascular coagulopathy (DIC).

PMID- 18340997
TI  - [Impact of nitric oxide synthase 3 on myocardial dysfunction in sepsis].
AB  - Septic shock is a complex syndrome that claims over 200,000 lives per year in the
      United States. While majority of the late mortality of sepsis appears to be due
      to multi-system organ failure, early death has been attributed either to
      distributive shock or to a cardiogenic form of septic shock. Overproduction of
      nitric oxide (NO), presumably by NO synthase 2 (NOS 2), has been implicated in
      the pathogenesis of cardiovascular dysfunction of sepsis. However, in clinical
      trials, NOS inhibitors that are not isoform-specific increased mortality in
      septic patients due to cardiac dysfunction, suggesting salutary effects of NOS 1
      and/or NOS 3. Recently, we found that cardiomyocyte-specific overexpression of
      NOS 3 prevents lipopolysaccharide (LPS)-induced myocardial dysfunction and
      mortality in mice. Myocardial mechanical efficiency was markedly impaired in wild
      type and NOS 3-deficient mice but not in mice with the NOS 3 transgene after LPS
      challenge. Improved myocardial function by excess NO during endotoxemia was
      associated with decreased myocardial oxidative stress, increased myofilament
      sensitivity to calcium, and increased phospholamban (PLB) phosphorylation. These
      results suggest that increased myocardial NO levels attenuate endotoxin-induced
      ROS production and increase total sarcoplasmic reticulum Ca2+ load and
      myofilament sensitivity to Ca2+ thereby reducing myocardial dysfunction and
      mortality in murine models of septic shock.

PMID- 18340998
TI  - [Lessons from SARS: a new potential therapy for acute respiratory distress
      syndrome (ARDS) with angiotensin converting enzyme 2 (ACE2)].
AB  - During several months of 2002, severe acute respiratory syndrome (SARS) caused by
      SARS-coronavirus (SARS-CoV) spread rapidly from China throughout the world
      causing more than 800 deaths due to the development of acute respiratory distress
      syndrome (ARDS). Interestingly, a novel homologue of angiotensin converting
      enzyme (ACE), termed angiotensin converting enzyme 2 (ACE2) has been identified
      as a receptor for SARS-CoV. ACE and ACE2 share homology in their catalytic domain
      and provide different key functions in the renin-angiotensin system. ACE cleaves
      angiotensin I to generate angiotensin II that is a key effector peptide of the
      system and exerts multiple biological functions, whereas ACE2 reduces angiotensin
      II levels and thus is a negative regulator of the system. Importantly, our recent
      studies using ACE2 knockout mice have demonstrated that ACE2 protects murine
      lungs from ARDS. Furthermore, SARS-CoV infections and the Spike protein of the
      SARS-CoV reduce ACE2 expression. Notably, injection of SARS-CoV Spike into mice
      worsens acute lung failure in vivo that can be attenuated by blocking the renin
      angiotensin pathway, suggesting the activation of pulmonary RAS influences the
      pathogenesis of ARDS and SARS.

PMID- 18340999
TI  - [Regulation of inflammatory responses by endothelial cells--understanding the
      molecular mechanism(s) and its therapeutic application to sepsis].
AB  - Endothelial cells are activated by shear-stress and inflammatory mediators that
      are capable of activating sensory neurons. Activated endothelial cells increase
      the production of nitric oxide and prostaglandins, thereby regulating
      inflammatory responses induced by various insults. Dysfunction of sensory neurons
      and excess inflammatory mediators released from activated neutrophils damage
      endothelial cells, thereby increasing inflammatory responses such as an increase
      in tumor necrosis factor production. Pulmonary endothelial dysfunction plays a
      critical role in the development of acute lung injury and shock, leading to multi
      organ failure. Determination of soluble E-selectin in serum samples of patients
      with sepsis predicts the future development of acute lung injury. Therapeutic
      agents that are capable of stimulating sensory neurons or inhibiting leukocyte
      activation might be useful in the treatment of severe sepsis especially when
      these agents are administered in the early stage of severe sepsis.

PMID- 18341000
TI  - [Oxidative stress and tissue injury].
AB  - Production of reactive oxygen species (ROS) and defense systems against them are
      balanced well in the living body. This balance is very important for the
      maintenance of physiological condition. The collapse of the balance such as in
      inflammation causes ROS toxicity and induces oxidative injury in various tissues.
      In this report, the relation between oxidative stress and tissue injury is
      discussed.

PMID- 18341001
TI  - [Alert cell strategy for severe sepsis].
AB  - Recent progress in cellular and molecular research has provided a new insight
      into the improvement of multiple organ dysfunction in sepsis. This paper
      introduces gene therapy targeting nuclear factor- kappaB, activator protein-1 and
      apoptosis of inflammatory alert cells in severe sepsis.

PMID- 18341002
TI  - [Assessment by logistic model of hemodynamic changes during general anesthesia].
AB  - The anesthesia induction with strong anesthetic agents generally reduces blood
      pressure. Cardiovascular agents used during anesthesia induce hemodynamic
      changes. The time courses of systolic (sBP) and diastolic blood pressure (dBP)
      and heart rate (HR) are expressed as sigmoidal curve. We have found that the
      hemodynamic changes can be precisely curve-fitted with a logistic function giving
      non-linear curve. The four parameters of the logistic function present the first
      asymptote, the last asymptote, the slope at the inflection point, and the time to
      the inflection point. Moreover, each logistic parameter is used for the effects
      of drug dose, age and sex differences of subjects on the hemodynamic change. In
      this review, we introduce the analyses with the logistic function for the changes
      in sBP, and dBP during preintubation period and HR, sBP, and dBP during infusion
      of landiolol hydrochloride, an ultra-short-acting beta1-adrenergic receptor
      blocking agent, which is used for subjects with tachycardia during general
      anesthesia. The logistic parameters are useful for assessing the hemodynamic
      response during general anesthesia. The assessment method of the hemodynamic
      change using the logistic model contributes much to the management of anesthesia.

PMID- 18341003
TI  - [Airway obstruction after tracheostomy in a neurologically impaired child].
AB  - A 14-year-old boy neurologically impaired was scheduled for tracheostomy under
      general anesthesia because of the prolonged tracheal intubation. He had twice
      received artificial respiration under tracheal intubation for aspiration
      pneumonia. During emergence from anesthesia, bucking occurred and suddenly the
      patient's lungs could not be ventilated. Neither anesthetic circuit nor
      tracheostomy tube were not functioning well, and airway obstruction was not
      relieved by manual and positive pressure ventilation within 40 mmHg. SpO2
      gradually decreased to 48%, resulting in bradicardia. However, it became possible
      to inflate the lungs immediately because of the respiratory effort decreased.
      SpO2 rapidly increased to normal range and heart rate recovered. The patient was
      suspected of having tracheomalacia as a result of flexible bronchoscopy performed
      through tracheostomy tube, revealing slight collapse of the trachea.
      Tracheomalacia can be a cause of sudden difficult ventilation in neurologically
      impaired children.

PMID- 18341004
TI  - [Anesthetic management of four patients with Fournier syndrome].
AB  - We experienced anesthetic managements of four patients with Fournier syndrome. In
      the anesthetic management of the patients with Fournier syndrome the following
      three points should be kept in mind; (a) the necessity of careful preoperative
      examination, (b) the better anesthesia, and (c) the careful postoperative care.

PMID- 18341005
TI  - [Anesthetic management of a patient with spinal muscular atrophy type III].
AB  - We report a 38-year-old man with Kugelberg-Welander disease who underwent triple
      arthrodesis for talipes equinovarus under combined spinal-epidural anesthesia
      supplemented with continuous intravenous infusion of propofol. There was no
      ventilatory disturbance, muscle weakness, or neurologic untoward event during
      perioperative period.

PMID- 18341006
TI  - [Anesthetic management for surgery of the ankle joint fracture in a patient with
      Ebstein's anomaly].
AB  - The authors describe the successful anesthetic management of a patient with
      Ebstein's anomaly and Wolff-Parkinson-White syndrome who underwent repair for
      foot joint fracture. Anesthesia was provided by combined spinal-epidural block to
      minimize hemodynamic changes which cause an increase in right-to-left shunt and
      hypoxemia. We estimated hemodynamic status using radial arterial pressure,
      central venous pressure and ECG from the start of anesthesia. During anesthesia,
      his vital signs were unchanged to any significant degree. The recovery was rapid
      and the postoperative course was uneventful.

PMID- 18341007
TI  - [Cases of femoral nerve palsy after radical prostatectomy].
AB  - Although postoperative femoral neuropathy is an uncommon complication occurring
      after pelvic surgery, we experienced several cases of femoral nerve palsy in
      patients after radical prostatectomy. All cases had neither previous vascular nor
      peripheral nerve disease. To investigate the possible etiology, we compared the
      difference in age, height, body weight, body mass index (BMI), duration of
      surgery, and volume of bleeding in patients with or without femoral nerve palsy.
      Although age and volume of bleeding were similar in groups, height, body weight,
      BMI, and duration of surgery in nerve palsy group (n = 5) were significantly
      larger than those without nerve palsy (n = 9). To evade these complications,
      inappropriate stretching and prolonged compression of the nerve during surgery,
      two major mechanisms of the neuropathy, were asked not to do to urological
      surgeons. In addition, intravenous patient-controlled analgesia (IV-PCA) was also
      used for postoperative analgesia instead of epidural analgesia. After these
      strategies, we found that the frequency of femoral nerve palsy had considerably
      decreased. Patients received physical therapy and showed nearly total
      neurological recovery. We report here unusual complication following major pelvic
      surgery, and discuss the possible etiology and some strategies for prevention of
      this injury.

PMID- 18341008
TI  - [Case of aprotinin-induced anaphylactic shock].
AB  - We report a case of anaphylactic shock caused by repeated use of aprotinin.
      Following re-administration of aprotinin at the beginning of repeated mitral
      valve replacement, the patient fell into shock state probably induced by
      anaphylactic reactions. Immediately, bispectral index (BIS) decreased from 40 to
      5, and near-infrared spectroscopy showed regional tissue oxygen saturation (rSO2)
      of frontal head decreasing from 64/56% (left/right) to 26/36%. Despite massive
      use of inotropes, the blood pressure, BIS and frontal rSO2 were not improved.
      After the immediate initiation of cardiopulmonary bypass, the perfusion pressure
      increased to 40 mmHg, and BIS and frontal rSO2 recovered to 45 and 70/61%,
      respectively. The patient had no significant neurological sequela after the
      surgery. We conclude that parallel changes of BIS and frontal rSO2 reflect acute
      global cerebral ischemia, and these parameters may be useful for decision making
      in the treatment of shock patients.

PMID- 18341009
TI  - [Intraoperative motor-evoked potential monitoring].

PMID- 18341010
TI  - [Occipital transtentorial approach to pineal and juxta-pineal tumors: guidance
      for safe surgery of the pineal region tumor].

PMID- 18341011
TI  - [Radiosurgery of hypothalamic hamartomas].
AB  - Hypothalamic hamartomas are relatively rare congenital tumors and present
      peculiar clinical symptoms such as convulsive and gelastic seizures, mental
      retardation, various abnormal behaviors as well as precocious puberty. We have
      treated 8 cases of symptomatic hypothalamic hamartomas with gamma knife surgery.
      There are 7 males and one female, ages ranging from 2 to 28 years (mean of 14.3
      years). All the patients presented with convulsive and gelastic seizures, and
      some of them showed abnormal behavior and precocious puberty. At radiosurgery
      hypothalamic tumors, 8 to 22 mm in diameter (mean 13.5 mm), were treated with the
      mean maximum and marginal doses of 32.9 Gy and 18.5 Gy respectively. In general
      an entire tumor coverage was intended, but a few were partially covered, because
      of the tumor size as well as nearby sensitive structures like the optic nerve and
      the hypothalamus. With the mean follow-up of 53.7 months after the radiosurgery,
      generalized seizures were well controlled in 6 out of 8 cases, but gelastic
      seizures were not always controlled. In order to achieve an excellent seizure
      control and a favorable neurological outcome, a marginal dose of more than 18 Gy
      with total tumor coverage is definitely required. In conclusion, radiosurgery can
      play a role in treating hamartomas since neurological outcome and seizure control
      are apparently improved.

PMID- 18341012
TI  - [Carotid artery stenting using the transbrachial approach: technical case
      report].
AB  - We described a case of endoluminal stent placement for cervical internal carotid
      artery stenosis in which access was obtained via the proximal portion of the
      right radial artery. A 70-year-old man with a history of arteriosclerosis
      obliterans presented for endoluminal revascularization of a stenosed left
      internal carotid artery. The transfemoral approach was not possible because of
      severe atherosclerosis of the bilateral common iliac arteries. An approach was
      attempted via the right radial artery. After placement of a 6F short sheath in
      the proximal portion of the right radial artery, the guiding catheter was
      positioned in the left common carotid artery using the coaxial catheter system.
      Stenting was successfully performed under distal protection. This novel approach
      should be considered for endovascular procedures for which access to the carotid
      artery is limited.

PMID- 18341013
TI  - [Operative case of eosinophilic granuloma of the skull with dural invasion].
AB  - Eosinophilic granuloma is the localized form of Langerhans' cell histiocytosis.
      There are several reports of magnetic resonance (MR) imaging of eosinophilic
      granuloma of the skull, however there are few reports about dural enhancement. We
      report an operative case of eosinophilic granuloma of the skull with dural
      invasion. A 42-year old man was admitted to our hospital. He was neurologically
      intact and there were no other osseous or soft tissue lesions. CT showed an
      osteolytic lesion in the left parietal bone. MR images showed the lesion as
      isointense on T1-weighted, and high intense on T2-weighted images. T1-weighted
      images with Gd-DTPA demonstrated the mass which was enhanced with dural surface
      and subgaleal tissue. The angiogram demonstrated a tumor stain fed by the left
      occipital artery. Bone scintigraphy demonstrated a solitary lesion showing
      peripheral uptake with a central defect. The patient underwent craniectomy with
      removal of the dura and a subgaleal lesion. Histological examination revealed
      characteristic eosinophilic granuloma with dural invasion. No recurrence of the
      lesion was demonstrated 6 months after surgery.

PMID- 18341014
TI  - [Case of venous angioma with chronic encapsulated hematoma].
AB  - We would like to report a rare case of a venous angioma with a chronic
      encapsulated hematoma, in a 31-year-old woman who was admitted to our hospital in
      November, 2005. Her neurological examination was noted to be normal. A CT was
      performed which showed an isodense mass in the left cerebellar hemisphere. This
      finding was confirmed on MR imaging, which showed a hyperintense mass on T1
      weighted imaging, and a hypo to isointense area on T2-weighted images. T1
      weighted images with Gd-DTPA enhancement revealed a dilated vein and, as a
      result, an angiogram was obtained. The venous phase demonstrated medullary veins
      converging on a central vein, which is usually known as a caput medusae. Follow
      up T1-weighted images with Gd-DTPA enhancement showed peripheral ring enhancement
      and expansion of the capsulated hematoma. Total removal of the hematoma and its
      capsule was performed in July, 2006. The hematoma was seen both inside and
      outside the tough capsule. A histological examination revealed that the capsule
      consisted of an outer collagenous layer and an inner granulated layer with
      deposits of hemosiderin. The hemorrhage rate of a venous angioma has been
      reported as between 0.22-0.61% per year. We thought that the initial small
      hemorrhage from the venous angioma resulted in the development of an encapsulated
      hematoma, and the total hematoma had expanded not only inside due to the
      hemorrhage of the capsule, but also outside because of the venous angioma.

PMID- 18341015
TI  - [Case of pineocytoma causing repetitive subarachnoid hemorrhage for 43 years].
AB  - A 61-year-old woman had suffered from severe headache and nausea over 20 times
      during the last 43 years. An subarachnoid hemorrhage (SAH) was detected by spinal
      puncture in some other hospitals, but the source of hemorrhage remained unknown
      in spite of repeated angiography. At the age of 61, she was diagnosed as having
      normal pressure hydrocephalus, and received a ventriculo-peritoneal shunt. She
      suffered from sudden headache 12 days after surgery. A CT scan showed a SAH and
      enlargement of the pineal mass. The tumor was totally removed via the occipital
      interhemispheric transtentorial approach and was diagnosed histologically as a
      pineocytoma. She has been free from SAH for three years since removal of the
      tumor. Pineal apoplexy should be considered as a cause of SAH.

PMID- 18341016
TI  - [Gene therapy for brain tumors: strategy utilizing herpes simplex virus type 1].

PMID- 18341017
TI  - Serological response to chemoprophylaxis in extended contacts in leprosy--a
      randomized controlled trial.
AB  - Chemoprophylaxis was carried out on high risk group of extended contacts of new
      leprosy cases in Nyaungdon Township, Ayeyarwaddy Division, Myanmar and
      serological response was followed up for two years. In September 2003, blood
      samples were collected from 829 contacts after getting informed consent and sera
      were tested for immunoglobulin M antibodies using NTP-BSA ELISA test. These 300
      seropositives were randomized to treated and non-treated groups. In each group
      102 each were enrolled in adults and 48 each in children. A single dose of ROM
      (rifampicin, ofloxacin and minocycline) and RMP (rifampicin) by body weight was
      administered to treated group of above 15 years and those below 15 years
      respectively. The vitamins were administered to non-treated group. The blood
      samples of all contacts were collected again in September 2004 and September 2005
      and ELISA was carried out on paired samples on one plate. The mean optical
      density (OD) titers before vs after chemoprophylaxis were 0.24 vs 0.10 and 0.20
      vs 0.09 in treated and non-treated group respectively in adults and 0.25 vs 0.11
      and 0.22 vs 0.11 respectively in children after one year. These were 0.24 vs 0.17
      and 0.20 vs 0.19 respectively in adults and 0.25 vs 0.19 and 0.22 vs 0.20
      respectively in children after two years. The difference of mean antibody titers
      before and after chemoprophylaxis in treated group was significantly reduced
      compared to non-treated group in adults but was not significant in children. The
      findings show that there is a significant role of chemoprophylaxis on serological
      response in the form of decreasing antibody titer among the adult group of
      extended contacts.

PMID- 18341018
TI  - Midfacial leprosy.
AB  - Leprosy is a chronic bacterial disease that has many clinical presentations. We
      are reporting a patient who presented with an erythematous plaque over the nose,
      which was proved to be due to leprosy. We think that this type of clinical
      feature is not a common presentation for leprosy.

PMID- 18341019
TI  - [Present leprosy situation in the world in 2007].
AB  - The epidemiological situation of leprosy is reported by the health division of
      each country to WHO. The reported data is collected by WHO and is immediately run
      on the Weekly Epidemiological Record. On this latest edition, data from the
      beginning of 2007 was reported. In almost all of the highly endemic countries,
      control activities have been integrated within the general healthcare system.
      However, Leprosy control programmes in many countries will need continued support
      from all partners to ensure that leprosy remains on the health agenda as long as
      necessary and that success does not lead to complacency.

PMID- 18341020
TI  - [Overseas medical cooperation for elimination of leprosy].
AB  - The typical leprosy doctor is disappearing in Japan. One of the reasons for this
      is that no more new cases arise among people of Japanese nationality.
      Furthermore, among people of other nationality living in Japan, occurrence of the
      cases has become rare. At the same time, it has become difficult to get a new
      medical person for leprosy field because the interest for the overseas medical
      cooperation has become diversified and there is a misunderstanding that the
      problem of leprosy in the world has been resolved. However we need to keep
      speaking out that there are still much more to be done. When we fortunately have
      someone who wishes to become a leprologist, his/her training is only possible in
      the very site of NGO in developing countries. One may start his/her work by
      passionate motivation of "living together", but actually he/she needs to be
      nurtured by people there. Another way to get involved is to first become a
      specialist of some sort, and then get in a medical system of a developing country
      as a narrow range specialist, and while serving them there, one can deepen
      his/her experiences as a whole leprosy. It is also important for us to think how
      we accept people who have worked overseas. We need to investigate and construct
      the supporting system for them. As long as leprosy patients exist in the world
      who are still suffering, we, as Japanese, need to make efforts in continuously
      sending people who live with them.

PMID- 18341021
TI  - Leprosy situation in Vietnam--reduced burden of stigma.

PMID- 18341022
TI  - [Leprosy links the world].

PMID- 18341023
TI  - [Status of collaboration in nursing and the care for leprosy patients].

PMID- 18341024
TI  - [Safety meal assistance--a trial of deglutition exercises for leprosy patients].

PMID- 18341025
TI  - [Leprosy patient comprehension using a perspective model and KOMI chart--clinical
      case conference].

PMID- 18341026
TI  - [Molecular mechanisms for intracellular parasitisation and exclusion in
      macrophage infected with Mycobacterium leprae].
AB  - It was previously demonstrated that TLR2 and CORO1A (TACO, Coronin 1, p57)
      localize phagosome membrane of macrophage. However, the functional relationship
      between TLR2 and CORO1A was not known. We show here that there is a functional
      counteraction between TLR2 and CORO1A.

PMID- 18341027
TI  - [Involvement of a cell adhesion molecule, CADM1/TSLC1 in oncogenesis and
      spermatogenesis].

PMID- 18341028
TI  - [Structural biology of receptor tyrosine kinase kit].

PMID- 18341029
TI  - [Epigenetic regulation of neural stem cell fate specification].

PMID- 18341030
TI  - [Lysophospholipid acyltransferase and platelet-activating factor (PAF)
      biosynthetic enzyme].

PMID- 18341031
TI  - [Progress in proton-sensitive GPCR research].

PMID- 18341032
TI  - [Cell cycle dependent dynamics of nuclear pores].

PMID- 18341033
TI  - [Molecular mechanisms of RAD6 DNA damage tolerance pathway in Saccharomyces
      cerevisiae].

PMID- 18341034
TI  - [RAD18 regulates DNA damage tolerance].

PMID- 18341035
TI  - [Cooperation between enzyme science and theoretical chemistry for a new paradigm
      in enzyme research].

PMID- 18341036
TI  - [Detection for subtype-specific genomic/genetic alterations in diffuse large B
      cell lymphoma (DLBCL)].

PMID- 18341037
TI  - [Clinicopathological analysis of patients with angioimmunoblastic T-cell lymphoma
      (AILT)].
AB  - We retrospectively analyzed the clinical course and prognosis of 11 patients with
      angioimmunoblastic T-cell Lymphoma (AILT). Median patient age was 62 years old
      (range 39 to 85). All patients were in clinical stage III or IV. Clinical
      features included B symptoms, hepatosplenomegaly, skin rushes, pleural effusion,
      ascites and polyclonal hypergammaglobulinemia. The disease can be classified into
      three categories based on histological findings: 3 cases of AILT with
      hyperplastic germinal centers, 4 cases of typical AILT, and 4 cases of AILT with
      numerous clear cells. As the initial therapy, 10 patients received combination
      chemotherapy and only 1 patient received autologous peripheral blood stem cell
      transplantation. Seven patients achieved CR and 4 showed PD. The response rate
      was 63% and the median survival time was 20 months. One patient survived in CR
      for 122 months. Patients with AILT demonstrating hyperplastic germinal centers
      and no bone marrow infiltration were able to achieve long-term survival. The
      survival time of AILT demonstrated a wide range. It was thought that further
      consideration of the prognostic factors and stratification was required.

PMID- 18341038
TI  - [Granulocyte transfusion for the treatment of prolonged pneumonia in a patient
      with MDS-RAEB-2 at allogeneic hematopoietic stem cell transplantation].
AB  - We report that granulocyte transfusion (GTX) was effective for prolonged
      pneumonia at allogeneic bone marrow transplantation. A 58-year-old man with MDS
      RAEB-2 was admitted to our hospital for allogeneic bone marrow transplantation.
      He was complicated with pneumonia, which was not improved with G-CSF and
      antibiotics. We therefore decided to perform a GTX transplantation. During the
      period of neutropenia, pneumonia did not deteriorate. A combination of allogeneic
      stem cell transplantation and GTX is expected not only to improve transplantation
      results but also to expand the adaptation for transplantation. However, detailed
      investigation of the effect of GTX in allogeneic stem cell transplantation should
      be performed, and more cases should be accumulated.

PMID- 18341040
TI  - [Cutaneous non-tuberculous mycobacterial infection following cord blood stem cell
      transplantation].
AB  - We describe a 4-year-old-girl with familial hemophagocytic lymphohistiocytosis
      (FHL) who developed disseminated cutaneous nontuberculous mycobacterial (NTM)
      infection after unrelated cord blood stem cell transplantation (uCBSCT). After
      transplantation, the patient developed steroid-refractory acute graft-versus-host
      disease, and was given methylprednisolone, cyclosporin and mycophenolate mofetil.
      Six months after uCBSCT, cutaneous lesions that looked like insect bites appeared
      and spread widely over the thighs. NTM infection was diagnosed by skin biopsy
      although no organism could be identified. Minocycline (MINO) and
      sulfamethoxazole/trimethoprim (ST) were administered. However, the cutaneous
      disease followed a course of remissions and exacerbations. One month after the
      skin biopsy, mycobacterium chelonae was detected by bacteriological culture of
      abscess drainage. Ten months after uCBSCT, the cutaneous lesions quickly
      progressed and the inguinal lymph nodes became enlarged and painful. Then the
      antibiotics were switched from MINO and ST to amikacin and clarithromycin (CAM)
      based on the results of mycobacterial susceptibility test. The cutaneous lesions
      gradually improved after continuous administration of CAM. Cutaneous NTM
      infection is rare, but it may occur in immunocompromised patients after SCT.

PMID- 18341039
TI  - [Successful treatment of azole-refractory Candida guilliermondii fungemia with a
      combination therapy of micafungin and liposomal amphotericin B].
AB  - Candida guilliermondii (C. guilliermondii) are uncommon, representing
      approximately 1% of all Candida infections, but have been reported to show a
      higher rate of drug-resistance and mortality rate than C. albicans. Current
      guidelines for treatment of non-albicans candidemia in neutropenic patients now
      recommend the use of amphotericin B or voriconazole (VRCZ). We describe here the
      successful treatment for a 58-year-old male with azole-refractory C.
      guilliermondii fungemia by combination with liposomal (L-AmB) and micafungin
      (MCFG) therapy. He was diagnosed as having mantle cell lymphoma, and treatment
      with HyperCVAD (Rituximab, cyclophosphamide, vincristine, doxorubicin,
      dexamethasone) was started. Despite prophylactic treatment with fluconazole, he
      developed fungemia due to C. guilliermondii 41 days after the start of
      chemotherapy. Positive blood culture and high levels of (1-->3)-beta-D-glucan
      persisted despite changing the treatment from fluconazole to voriconazole.
      Although L-AmB was also added to VRCZ, the clinical symptoms worsened. When MCFG
      was combined with L-AmB, the symptoms and data dramatically improved. Thus,
      combination therapy consisting of MCFG and L-AmB might be more effective against
      candidemia that is refractory to azole than combination therapy with VRCZ and L
      AmB.

PMID- 18341041
TI  - [Graves' disease with splenomegaly and pancytopenia, mimicking B-cell
      lymphoproliferative disease].
AB  - A 48-year-old woman was referred to our hospital because of fever and general
      fatigue. Peripheral blood analysis showed a hemoglobin level of 82 g/l, a white
      blood cell count of 1.95 x 10(9)/l and a platelet count of 80 x 10(9)/l. There
      were 9% CD5-positive B-cells in peripheral blood and 35% CD10-positive B-cells in
      bone marrow. The patient had a high serum soluble interleukin-2 receptor (SIL-2R)
      level of 5,185 U/ml and splenomegaly. Lymphoproliferative disease was suspected,
      however monoclonal rearranged band of immunoglobulin heavy chain was not
      detected. She also showed hyperthyroidism, Graves' disease and then treatment
      with thiamazole started. However, the treatment was stopped because of
      agranulocytosis and she received subtotal thyroidectomy. After treatment for
      hyperthyroidism, serum SIL-2R level decreased to 504 U/ml and pancytopenia
      gradually improved. Fifteen months postoperatively, the percentage of CD5
      positive B-cells in peripheral blood and CD10-positive B-cells in bone marrow
      decreased to 8% and 2%, respectively. This clinical course suggests that
      polyclonal B-cell proliferation was caused by hyperthyroidism.

PMID- 18341042
TI  - [Additional chromosomal changes in impaired chimeric analysis of a patient with
      relapsed leukemia after bone marrow transplantation].
AB  - Chimerism analysis by polymerase chain reaction amplification of short tandem
      repeats (PCR-STR) has become a routine diagnostic procedure for evaluating grafts
      and assessing the likeliness of original disease recurrence after allogeneic stem
      cell transplantation. Following a sex-mismatched hematopoietic stem cell
      transplantation (HSCT), we monitored the clinical course of a 61-year old male
      AML M6 patient with trisomy 8 using PCR-STR with a TH01 locus on 11p15 and
      fluorescence in situ hybridization (FISH) analysis specific for alpha satellite
      DNA on chromosome 8. Ten months after HSCT, FISH analysis showed 24.8% recipient
      cells, but PCR-STR demonstrated 100% donor type chimerism. Further XY FISH
      analysis of May-Grunwald-Giemsa-stained bone marrow samples clearly demonstrated
      relapse of the original disease and G-banding analysis of bone marrow samples at
      relapse showed that an additional chromosomal abnormality, del(11) (p10), had
      deleted the PCR-STR detection site in all recipient type cells. As such,
      clinicians should consider the possibility that unexpected karyotype changes may
      invalidate PCR-STR analysis findings, especially when conflicting results appear
      among chimerism analyses.

PMID- 18341044
TI  - [A 4-year-old girl showing lower limb pain and dysbasia].

PMID- 18341043
TI  - [My carrier as a researcher].

PMID- 18341046
TI  - [Biological clocks in brain and body].

PMID- 18341045
TI  - [Difference in susceptibility and vulnerability to seizures between immature
      brain and mature brain].

PMID- 18341047
TI  - [Functional role of redox for neuronal disease].

PMID- 18341048
TI  - [The matrix cell and the development of the brain map].

PMID- 18341049
TI  - [Classification of acute encephalopathy with emphasis on acute encephalopathy
      with febrile convulsive status].

PMID- 18341050
TI  - [A concept of acute encephalopathy with febrile convulsive status epilepticus
      (AEFCSE) and theophylline as one of its precipitating causes].

PMID- 18341051
TI  - [Neuroradiological findings in acute encephalopathy with biphasic seizures and
      late reduced diffusion (AESD)].

PMID- 18341052
TI  - [Acute infantile encephalopathy predominantly affecting the frontal lobes
      (AIEF)].

PMID- 18341053
TI  - [Cytokine analysis of acute encephalopathy following prolonged febrile seizures].

PMID- 18341054
TI  - [Status epilepticus type of acute encephalopathy from the viewpoint of serum and
      cerebrospinal fluid cytochrome c levels].

PMID- 18341055
TI  - [Treatment for seizures during theophylline medication].

PMID- 18341056
TI  - [Retrospective study of the usefulness of phenobarbital injection in children].

PMID- 18341057
TI  - [Valproate sodium is effective as prophylactic therapy for cyclic vomiting
      syndrome in a case].

PMID- 18341060
TI  - NZNO members favour workplace educational opportunities.

PMID- 18341061
TI  - Moving from an academic setting to clinical practice.

PMID- 18341062
TI  - Using nursing skills to relieve the symptoms of Parkinson's disease. Interview by
      Anne Manchester.

PMID- 18341063
TI  - Getting back to nursing.

PMID- 18341064
TI  - To sink or swim?

PMID- 18341065
TI  - Making the preceptorship model work better for students.

PMID- 18341066
TI  - Professional focus. Respecting caregivers and their work.

PMID- 18341067
TI  - Industrial focus. Respecting caregivers and their work.

PMID- 18341069
TI  - Protecting and promoting the rights and welfare of students.

PMID- 18341070
TI  - Nursing and pre-registration nursing education under the spotlight again.

PMID- 18341071
TI  - A qualitative investigation of the palliative care needs of terminally ill people
      who live alone.
AB  - This paper investigates the support needs of people living alone with a terminal
      illness from a client perspective. In depth, interviews were conducted with 11
      clients from Silver Chain Hospice Care in Western Australia to capture their
      personal experiences of managing at home alone and to assess their physical,
      social and emotional needs. Findings provided useful insights with respect to
      many of the motivations, beliefs and wishes of individuals who endeavour to cope
      on their own with minimal assistance. The needs of these individuals are
      practical, emotional, physical and existential. At the heart of these concerns is
      a strong need to be independent and maintain a sense of dignity at end of life.

PMID- 18341072
TI  - Implications for Australian practice of North American guidelines for the support
      of the family in patient-centred intensive care.
AB  - Patient-centred care, in which health care professionals inform patients and
      families, maintain active involvement in decision making, coordinate care across
      disciplines, provide families with physical comfort and emotional support and
      ensure care is culturally sensitive, is recommended over clinician- or disease
      centred care for better patient outcomes. Patients in intensive care are often
      too ill to participate in communication and decision making, so the patient's
      family should be involved in communication and decision making about the
      patient's care. The Society of Critical Care Medicine published clinical practice
      guidelines for the support of the family in the patient-centred intensive care
      unit. The purpose of this paper is to assess whether the 42 recommendations in
      the guidelines are valid and applicable in Australia. We used a recognised
      framework for evaluation of clinical practice guidelines. It was found that the
      guidelines were developed systematically using accepted methods of guideline
      development as much as possible. An extensive literature review was conducted and
      publications containing all levels of evidence were considered for inclusion.
      There were some weaknesses in the guideline development, especially lack of
      consultation with patients and families and a lack of high-level evidence,
      however the authors have provided comprehensive recommendations to guide all
      aspects of patient-centred care. We conclude that the recommendations are largely
      applicable to the patients and families receiving treatment and support within
      intensive care units in Australia. Where strong evidence is lacking, the
      recommendations should be a stimulus to conduct studies that test interventions
      that may benefit intensive care patients, their families, and intensive care
      staff.

PMID- 18341073
TI  - Designing nursing interventions.
AB  - The development of nursing interventions that demonstrate the link between
      nursing actions and patient outcomes is a high priority for nursing research. The
      development of intervention research frequently focuses on the methods used to
      test the intervention while less attention is placed on rigor in intervention
      development and design. The purpose of this paper is to provide thinking points
      for researchers considering the development of nursing interventions. The
      thinking points were developed from the limited literature on this topic in
      synthesis with the authors own experiences of designing nursing interventions.
      Adoption of a systematic approach to intervention testing is advocated along with
      a step-wise intervention development process. This process calls for attention to
      problem definition, conceptual underpinnings, desired outcomes and measures and
      evidence-based content along with careful consideration of delivery methods, dose
      and attention to protecting the integrity of the intervention during testing. The
      approach advocated will help to ensure that nursing intervention research makes a
      useful contribution to the development of nursing practice.

PMID- 18341074
TI  - Servant leadership in nursing: a framework for developing sustainable research
      capacity in nursing.
AB  - In the current professional climate, research activities are highly valued with
      nurses in all sectors actively encouraged to participate. However, working
      environments for many nurses are such that it can be difficult to privilege
      research activities in any sustained way. A number of organisational challenges
      coalesce to impede participation in research activities, including limited
      resources, lack of skills, knowledge and opportunities, and a culture of
      individualism. Strong, effective research leadership is essential to help mediate
      some of these negative aspects of organisational life, and promote creative
      environments to facilitate the development of research capacity. Servant
      leadership is a service-oriented approach that focuses on valuing and developing
      people, and offers a participatory and collaborative framework within which to
      build creative and productive research communities. Such communities can
      encourage connectedness between people, deepen the capacity for supportive
      collegiality, and foster a holistic social learning milieu to support researchers
      of all levels, including early career researchers and research higher degree
      candidates.

PMID- 18341075
TI  - Effect of seven hours intermittent suckling and flavour recognition on piglet
      performance.
AB  - A low feed intake during the first days after weaning is predisposing for weaning
      diarrhoea and weight loss. In this experiment we tried to increase the feed
      intake of the piglets after weaning by stimulating the solid feed intake during
      the last two weeks before weaning by separating them from the sows for 7 h/d. In
      addition, the effect of flavour recognition and the interaction of flavour
      recognition with intermittent suckling were tested. In two consecutive weaning
      rounds, sows were divided over two compartments with 7 to 10 sows each. They were
      assigned to one of four treatments in a two factorial design: control
      housing/control feed (n = 7); control housing/ flavoured feed (n = 8);
      intermittent suckling/control feed (n = 7); intermittent suckling/ flavoured feed
      (n = 9). After weaning, for each round 3 pens of 6 pigs were selected per
      treatment group. All these piglets received the same feed with the same flavour
      at the same concentration. Contrary to the expectations, intermittent suckling
      decreased the solid feed intake during the last two weeks before weaning. Flavour
      addition to the creep feed did not increase feed intake or other performance
      parameters before and after weaning, nor did it interact with intermittent
      suckling. Although after intermittent suckling pigs ate less creep feed before
      weaning, they did not perform worse after weaning. However, to increase feed
      intake after weaning, longer periods of separation might be necessary.

PMID- 18341076
TI  - Effects of dietary energy and lysine intake during late gestation and lactation
      on blood metabolites, hormones, milk composition and reproductive performance in
      multiparous sows.
AB  - This study was conducted to investigate the effects of different energy and
      lysine intake on reproductive performance of multiparous sows during late
      gestation and lactation. Thirty-six sows were allocated to six dietary treatments
      in a 3 x 2 factorial arrangement and each treatment had six replicates. Three
      energy levels and two lysine levels were used during late gestation and
      lactation. The results demonstrated that higher lysine intake improved (p < 0.05)
      the body condition of sows during both periods and their reproductive performance
      during lactation. Both, dietary energy and lysine level had a significant effect
      (p < 0.05) on the composition of colostrum and milk. In general, dietary
      treatments had no effect on blood metabolites and hormones. These results suggest
      that energy levels recommended by the National Research Council (1998) for sows
      are enough; however, higher lysine levels than those recommended could improve
      reproductive performance during late gestation and lactation in multiparous sows.

PMID- 18341077
TI  - Effects of fermentation products of Ganoderma lucidum on growth performance and
      immunocompetence in weanling pigs.
AB  - The purpose of this study was to test fermentation, for its products of a Chinese
      medicinal mushroom, Ganoderma lucidum, cultured by submerged fermentation for its
      effect on growth performance and immunocompetence in weanling piglets. In
      Experiment 1, 72 weanling piglets were allotted to one of four treatments
      receiving these fermentation products (GLF, expressed as amount of beta-glucans)
      at 0 (control), 50, 100, and 150 mg/kg feed for 4 weeks. The results showed that
      at a supplementation level of 50 mg/kg feed, GLF caused the best growth
      performance, the highest pseudorabies antibody titre, and a decrease of blood
      glucose level. It was also demonstrated that GLF up-regulated the cell-mediated
      immune response related cytokines (IL-2, IFN-gamma, and TNF-alpha) expression in
      different lymphoid tissues. After challenging with porcine circovirus (PCV) type
      2 (Experiment 2), a supplementation with 50 mg GLF per kg feed also inhibited PCV
      2 virus amplification, and ameliorated lymphocyte depletion in different lymphoid
      tissues. Conclusively, feed supplemented with GLF at 50 mg/kg could be beneficial
      to counteract the physiological stress in weanling piglets.

PMID- 18341078
TI  - Effect of adding extracted hesperetin, naringenin and pectin on egg cholesterol,
      serum traits and antioxidant activity in laying hens.
AB  - In this study three feed additives (hesperetin, naringenin and pectin) for laying
      hens were investigated on their influence on the egg yolk cholesterol, serum
      traits and antioxidant activities in hens. Additives were extracted from citrus
      and grapefruit peels and contained 31.5% crude hesperetin, 39% crude naringenin
      and 60% galacturonic acid (pectin). Eighty 30-week-old Leghorn laying hens were
      randomly assigned to four groups and received, for two months, a control diet or
      diets with 0.05% hesperetin, 0.05% naringenin or 0.5% pectin. All additives
      reduced the egg yolk cholesterol level significantly. Feeding diets with added
      flavonoids (hesperetin and naringenin) increased the yolk weight and the ratio of
      yolk weight/egg weight and the blood serum superoxide dismutase (SOD) activity
      was elevated. Total antioxidation capacity, the level of thiobarbituric acid
      reactive substances and superoxide scavenging capacity in the naringenin group
      were greater than in the control group. Supplemented flavonoids reduced the serum
      cholesterol level significantly, while serum triglyceride concentration in the
      naringenin and pectin groups was reduced. Addition of flavonoids resulted in an
      enhanced cholesterol level in excreta. The results of this study indicated that
      intake of hesperetin, naringenin and pectin extracted from citrus and grapefruit
      peel in laying hens diet, may exhibit positive effects.

PMID- 18341079
TI  - Late gestational nutrient restriction: effects on ewes' metabolic and homeorhetic
      adaptation, consequences for lamb birth weight and lactation performance.
AB  - We investigated the effect of 50% nutrient restriction during the last 6 weeks of
      gestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, beta
      hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb
      birth weight and ewes' lactation performance. Plasma metabolite and hormone
      concentrations in restricted ewes suggest that maternal tissues were being
      mobilised. Despite the ewes' adaptations their lambs weighed significantly less
      at birth. Furthermore, colostrum and milk yields were markedly reduced up until
      the latest measurement at 3 weeks post partum despite ad libitum access to feed.
      Reduced milk yields coincided with reduced plasma IGF-1 concentration pre partum
      in nutrient restricted ewes indicating, that mammary gland development may have
      been compromised. The present data suggest that leptin is not involved in the
      regulation of early lactation changes in feed intake and energy balance. It is
      concluded that severely reduced nutrient availability in late gestation affects
      fetal growth in utero and has a prolonged negative effect on lactation
      performance.

PMID- 18341080
TI  - Influence of feeding whole sunflower seed and extruded linseed on production of
      dairy cows, rumen and plasma constituents, and fatty acid composition of milk.
AB  - Holstein cows were fed total mixed rations (TMR) supplemented with protected palm
      fat (PPF), whole sunflower seed (WSS) or extruded linseed (ELS) for 100 days.
      Percentage of dietary crude fat was 5.3, 5.1 and 5.1, respectively. Diet had no
      (p > 0.05) effect on feed intake, milk yield or milk protein content. Percentage
      of milk fat and yield of fat--corrected milk were significantly increased when
      diets were supplemented with WSS and ELS. Feeding PPF resulted in the lowest (p <
      0.05) ruminal concentration of volatile fatty acids. No significant dietary
      effect on plasma characteristics was observed. Concentration of polyunsaturated
      fatty acids (PUFA) was higher (p < 0.05), and PUFA n-6/n-3 ratio lower (p <
      0.05), in the milk fat from cows fed ELS compared to WSS. Supplementation of TMR
      with oilseeds compared to PPF increased the content of CLA in milk fat (p <
      0.005) and decreased its atherogenicity, primarily due to a significant reduction
      of palmitic acid concentration. Both oilseeds significantly improved the
      spreadability index of manufactured butter. ELS, but not WSS, increased the
      susceptibility of milk fat to oxidation (p < 0.05). It can be concluded that
      feeding of oilseeds to dairy cows improved nutritional quality of milk fat, with
      supplementation with ELS producing an even more desirable milk fatty acid profile
      than WSS supplementation.

PMID- 18341081
TI  - Effects of malate supplementation on acid-base balance and productive performance
      in growing/finishing bull calves fed a high-grain diet.
AB  - This study investigated the effects of malate supplementation on blood acid-base
      balance and serum lactate levels in a 137-day feedlot experiment with bull
      calves. Animals were allotted to one of two experimental groups: (1) A control
      group (no supplementation), and (2) a group receiving a salt of DL-malic acid.
      Blood pH, pCO2, HCO3-, base excess, serum L-lactate and productivity parameters
      were evaluated. Our data reveal that under the conditions of the present
      experiment malate supplementation did not have any significant effect on
      productivity parameters by comparison with non-supplemented animals. As regards
      acid-base balance, no significant effects attributable only to malate were
      observed. In conclusion, the time-course and the overall means of serum L-lactate
      for both groups in both growing and finishing periods (0.44 +/- 0.04 mmol/l and
      0.39 +/- 0.02 mmol/l, respectively, for control animal; and 0.54 +/- 0.03 mmol/l
      and 0.49 +/- 0.01 mmol/l, respectively, for supplemented animals) suggests that
      malate does not have any beneficial effects in animals fed a diet of similar
      characteristics to that given in this study.

PMID- 18341082
TI  - Nitrogen excretion in rats on a protein-free diet and during starvation.
AB  - Nitrogen balances (six days) were determined in male Wistar rats during feeding a
      diet with sufficient protein or a nearly protein-free diet (n = 2 x 24), and then
      during three days of starvation (n = 2 x 12). The objective was to evaluate the
      effect of protein withdrawal on minimum nitrogen excretion in urine (UN),
      corresponding to endogenous UN, during feeding and subsequent starvation periods.
      The rats fed the protein free-diet had almost the same excretion of urinary N
      during feeding and starvation (165 and 157 mg/kg W(0.75)), while it was 444 mg/kg
      W(0.75) in rats previously fed with protein, demonstrating a major influence of
      protein content in a diet on N excretion during starvation. Consequently, the
      impact of former protein supply on N losses during starvation ought to be
      considered when evaluating minimum N requirement necessary to sustain life.

PMID- 18341083
TI  - Health care coverage in America: the penalty of the uninsured, insured and
      physician.

PMID- 18341084
TI  - Update on coeliac disease and type 1 diabetes mellitus in childhood.
AB  - The increased prevalence of coeliac disease (CD) among children with type 1
      diabetes mellitus (DM1) implies that there is more than a simple association. A
      link between the gut immune system and DM1 has been suggested both in animal
      models and in humans. We review the literature on the epidemiology and genetic
      and clinical aspects shared by these two diseases and speculate on the role of
      gluten on the possible relationship between CD and DM1, on the basis of recent
      animal and human studies. The data suggest a failure in oral tolerance mechanisms
      in DM1 other than that in CD. It remains to be understood why only a small
      proportion of patients with DM1 proceed to the production of coeliac-associated
      antibodies and to overt enteropathy.

PMID- 18341085
TI  - McCune-Albright syndrome.

PMID- 18341086
TI  - Thyroid function in extremely premature neonates: a reference database.

PMID- 18341087
TI  - Thyroid function in preterm infants 27-29 weeks of gestational age during the
      first four months of life: results from a prospective study comprising 80 preterm
      infants.
AB  - AIM: Assessment of thyroid function in preterm neonates (PTN) 27-29 weeks of
      gestational age. PATIENTS AND METHODS: 80 PTN, gestational age 27 weeks in 24, 28
      weeks in 28, and 29 weeks in 28. Neonates were classified as healthy (n=17) or
      sick (n=63). Measurement of serum TSH, free T4, T4, T3 and rT3 in the mother and
      in the cord at the time of delivery, and in the infant at 1 hour, 24 hours, 1
      week, 3 weeks, and 2 and 4 months of postnatal age. RESULTS: In healthy and sick
      preterms, TSH values peaked at 1 hour and decreased thereafter. Healthy PTN
      presented a peak in free T4 values at 24 hours that was not observed in sick
      neonates. Sick PTN had a lower TSH peak and lower free T4 values at 24 hours and
      1 week than healthy ones (p < 0.05). Healthy PTN 27-29 weeks had lower TSH peak
      at 1 hour and lower free T4, T3 and T4 values during the first 2 months than
      healthy PTN 30-35 weeks (PTN30-35w) previously evaluated (p < 0.05). However, at
      all postnatal times healthy preterms had free T4 values above -2 SD of the mean
      values of healthy PTN30-35w. A wide range of free T4 values was observed in the
      sick group. Free T4 values above -2 SD of the mean values of healthy PTN30-35w
      were detected in a high proportion of sick PTN (58.3% at 24 hours, 73.5% at 1
      week, 93.9% at 3 weeks, 85.1% at 2 months and 100% at 4 months). CONCLUSIONS:
      Prematurity and disease influence thyroid function, and consequently thyroid
      function should be individually assessed in preterms 27-29 weeks of gestation
      during the first 2 months of life.

PMID- 18341088
TI  - Adrenal steroid concentrations in children seven to seventeen years of age.
AB  - During puberty, serum steroid concentrations change dramatically. The objective
      of this study was to determine the adrenal steroid concentrations in children
      from 7 to 17 years of age. Tanner stage was determined in each child by physical
      examination. 11-Deoxycortisol, pregnenolone, 17-hydroxypregnenolone, 17
      hydroxyprogesterone and testosterone were quantified by liquid chromatography
      tandem mass spectrometry (LC-MS/MS). Androstenedione and dehydroepiandrosterone
      sulfate were measured by immunoassay. The median and central 95% of the steroid
      concentrations were determined for age, gender, and Tanner stage. Except for 11
      deoxycortisol, all of the steroids exhibited an increase in concentration after
      age 7-9 years in both boys and girls. 11-Deoxycortisol, which is made exclusively
      in the adrenal cortex, declined with age and Tanner stage. This suggests that a
      rise in gonadal function and decreased efficiency of 11beta-hydroxylase with age
      may contribute to an increase in the remaining steroids. Testosterone
      concentrations increased more dramatically in boys, but increases were seen with
      each Tanner stage in girls.

PMID- 18341089
TI  - Kinetic profiles of 18 systemic pro- and anti-inflammatory mediators during and
      following exercise in children.
AB  - While acute changes in systemic pro-/antiinflammatory cytokines occur with
      exercise, individual kinetics during and following exercise remain unclear;
      particularly, information is scarce regarding children. This study investigated
      the exercise-induced kinetic profiles of major pro-/anti-inflammatory mediators
      in 21 healthy children (13.9 +/- 0.8 yr, 7 M/14 F). Exercise was 30 min of
      intermittent cycling at approximately 80% VO2max. Multiple blood samples were
      drawn at baseline, during, and following exercise for cytokines assay. IL-1alpha,
      IL-6, IL-17, IL-8, IP-10, MIP-1alpha, and MIP-1beta initially decreased (nadir:
      14-19 min into exercise) and subsequently exceeded baseline levels (peaks: 20-24
      min into exercise). TNF-alpha, IL-12p70, IL-1RA, IL-4, EGF, TGF-alpha, GM-CSF,
      Eotaxin, and MCP-1 were moderately and persistently decreased throughout. VEGF
      was unchanged; sCD40L was elevated during exercise and recovery. Our results
      indicate that key immunomodulators display non-linear, biphasic kinetic profiles
      in response to exercise, suggesting that detection of exercise-induced changes
      over baseline may depend on exercise duration and sampling timing.

PMID- 18341090
TI  - Administration of arginine plus growth hormone releasing hormone to evaluate
      growth hormone (GH) secretory status in children with GH deficiency.
AB  - BACKGROUND: Diagnosis of growth hormone deficiency (GHD) in childhood is usually
      based on growth hormone (GH) response to at least two provocative stimuli. The
      aim of this study was to determine whether sequential administration of arginine
      (Arg) plus GH releasing hormone (GHRH) could be a useful tool in evaluating GHD
      in children. METHODS: Thirty patients with short stature (mean age 9.0 years)
      with decreased growth rate were tested for GHD with Arg and the insulin tolerance
      test (ITT). Patients with confirmed GHD (peak GH <8 ng/ml) were subsequently
      tested with Arg + GHRH. RESULTS: Maximum GH stimulation for Arg and ITT was 6.3
      (1.0-7.8) and 6.7 (0.5-7.7) ng/ml, respectively. Peak GH for the Arg + GHRH test
      was 36.3 (4.3-84.5) ng/ml and significantly different from the other provocative
      tests. Peak GH values for the three tests were not significantly correlated
      between tests or with clinical parameters. There were no significant differences
      in Arg + GHRH results between children with or without abnormal hypothalamic
      pituitary MRI scans. CONCLUSION: Arg + GHRH gave higher GH levels than insulin or
      Arg alone. Because of the different causes of childhood GHD (hypothalamic and/or
      pituitary dysfunction), the Arg + GHRH test is unsuitable .for evaluating GHD and
      deciding whether GH replacement therapy is indicated.

PMID- 18341091
TI  - The effects of recombinant human growth hormone on linear growth in children with
      Crohn's disease and short stature.
AB  - BACKGROUND/AIMS: The efficacy of recombinant human growth hormone (rhGH) in
      treating the growth failure associated with Crohn's disease (CD) is unclear.
      METHODS: Retrospective data analysis at 12 months before (T-12), 6 months before
      (T-6), at baseline (T+0), 6 months after (T+6) and 12 months after (T+12) rhGH
      treatment in seven patients with CD (five males). RESULTS: Median chronological
      age (CA) and median difference between CA and bone age was 15.9 yr (range, 13.0
      to 17.9) and 1.7 yr (-0.7 to 3.3), respectively. Median dose of rhGH at T+0 was
      0.23 mg/wk (0.15 to 0.31). Pubertal status remained unchanged in 6/7 patients.
      Median albumin and C-reactive protein (CRP) were similar at T+0 and T+6. Median
      height SDS at T+0, T+6 and T+12 was -2.2 (-4.0 to -1.5), -1.9 (-4.1 to -0.8), 
      1.9 (-4.1 to -0.7), respectively (NS). Median height velocity (HV) SDS at T+0 and
      T+6 was -2.5 (-4.8 to 1.4) and -0.9 (-5.3 to 3.4), respectively (NS). There was a
      positive correlation between percentage change in HV SDS at T+6 and dose of rhGH
      at T+0 (r = 0.8, p = 0.03). CONCLUSION: Introduction of rhGH therapy was
      associated with a cessation in the deterioration in linear growth. However, an
      improvement in height SDS was not observed over the period of the study. Future
      studies should explore the efficacy of a higher dose of rhGH in CD.

PMID- 18341092
TI  - Foot length before and during insulin-like growth factor-I treatment of children
      with laron syndrome compared to human growth hormone treatment of children with
      isolated growth hormone deficiency.
AB  - OBJECTIVE: To compare foot length deficits between patients with Laron syndrome
      (LS) (primary growth hormone [GH] insensitivity) and congenital isolated GH
      deficiency (IGHD) and their response to replacement therapy with insulin-like
      growth factor-I (IGF-I) and hGH, respectively. DESIGN: Data for the study were
      collected from the records of nine children with LS (3 M, 6 F) 7.8 +/- 4.8 years
      old (mean +/- SD), and nine children with IGHD (3 M, 6 F), 3.8 +/- 3.3 years old.
      Fifteen non-treated adult patients with LS were also included in the study.
      METHODS: Measurements of foot length were recorded without treatment and
      monitored during 9 years of treatment in the children and in the untreated adult
      patients. For statistical analysis the non-parametric Mann-Whitney U test was
      used. RESULTS: With almost similar basal values in growth deficit and pre
      treatment growth velocities, the achievements towards norms after 9 years of
      treatment were greater in the patients with IGHD than in the patients with LS:
      foot length reached -1.4 +/- 0.8 vs. -3.3 +/- 1.0 SDS (mean +/- SD), and body
      height -2.2 +/- 1.0 vs. -3.9 +/- 0.5 SDS. The difference between the two groups
      could be due to the initiation of replacement therapy in the patients with IGHD
      at a younger age. Adult foot size of untreated patients with LS is small but less
      retarded than the height deficit. CONCLUSIONS: Both IGF-I and hGH are potent
      growth stimulating hormones of linear growth and acrae as exemplified by foot
      growth.

PMID- 18341093
TI  - No evidence for additional imprinting defects in Silver-Russell syndrome patients
      with maternal uniparental disomy 7 or 11p15 epimutation.
AB  - Silver-Russell syndrome (SRS) is mainly characterised by intrauterine and
      postnatal growth retardation (IUGR and PNGR), asymmetry, clinodactyly V and
      craniofacial abnormalities. More than 35% of patients carry a hypomethylation of
      the telomeric imprinting centre region 1 (ICR1) in 11p15; single patients show a
      maternal duplication of 11p15. An additional 7-10% of patients with SRS have
      maternal uniparental disomy of chromosome 7 (mUPD7). Another disorder caused by
      epigenetic defects is transient neonatal diabetes mellitus (TNDM) which is
      associated with loss of methylation (LOM) in 6q24. After detecting methylation
      loss at multiple imprinted loci in patients with TNDM, Mackay et al. recently
      proposed the existence of a maternal hypomethylation syndrome presenting as TNDM.
      They therefore concluded that patients with other disorders associated with LOM
      at one (maternally) methylated locus might also carry LOM at multiple loci.
      Similar observations have also been reported in Beckwith-Wiedemann syndrome
      (BWS): nearly 25% of patients displayed abnormal methylation patterns of ICRs
      additional to those in 11p15. To show whether general hypomethylation is a common
      phenomenon in imprinting disorders we carried out methylation analyses for the
      imprinted regions 14q32, 6q24 and the centromeric imprinting region ICR2 on 11p15
      for 10 patients with SRS carrying mUPD7 and 22 patients with LOM at the telomeric
      imprinting region ICR1. We showed that further epigenetic defects did not occur
      in the groups of SRS with LOM of ICR1 or mUPD7, and that these subentities do not
      belong to the diseases with a general hypomethylation defect, such as TNDM and
      BWS.

PMID- 18341094
TI  - Precocious puberty in a girl with floating-harbor syndrome.
AB  - Floating-Harbor syndrome (FHS) is a rare genetic disorder characterized by short
      stature, delayed bone age, mild to moderate mental retardation, speech problems,
      and peculiar craniofacial features. In these patients pubertal development has
      been reported to be normal. In this paper, we describe a girl with FHS who
      developed precocious puberty. FHS diagnosis was made at 2 years 5 months on the
      basis of peculiar clinical features. At 7 years 7 months, the girl began pubertal
      development; her height was 112.5 cm (-2.42 SDS) and pubertal staging was B2 PH2
      AH1. LHRH test underlined LH and FSH peak values of 11.7 mIU/ml and 6.2 mIU/ml,
      respectively. Plasma levels of 17beta-estradiol were normal (8.5 pg/ml).
      Ophthalmological and neurological examinations, including nuclear magnetic
      resonance imaging of the brain, were normal. Treatment with gonadotrophin
      releasing hormone analogue was begun. At 10 years 1 month, because of reduced
      height velocity, her growth hormone secretion was evaluated with diagnosis of
      neurosecretory dysfunction; hGH therapy was begun. The patient showed a good
      response to hGH treatment, reaching a normal adult height (156.1 cm; -1.20 SDS).
      This report suggests that, in patients with FHS, precocious puberty should be
      taken into consideration; in these patients, a careful endocrinological followup
      for the possible presence of growth and pubertal disorders is needed.

PMID- 18341095
TI  - The variable clinical phenotype of liver glycogen synthase deficiency.
AB  - We report two new cases of liver glycogen synthase deficiency (GSD0). The first
      patient presented at the age of 8 months with recurrent hypoglycemic seizures.
      The second patient presented at 14 months with asymptomatic incidental
      hyperglycemia. Glucose monitoring in both patients revealed daily fluctuations
      from fasting hypoglycemia to postprandial hyperglycemia. Genetic analysis of the
      GYS2 gene confirmed the diagnosis. GSD0 is more common than previously assumed.
      Recognition of the variable phenotype spectrum of GSD0 and routine analysis of
      GYS2 are essential for the correct diagnosis.

PMID- 18341096
TI  - HIM legislation--stuck in a moment?

PMID- 18341097
TI  - How legal is your EHR? Identifying key functions that support a legal record.

PMID- 18341098
TI  - Legal EHR roundtable. Views and needs differ by stakeholder.

PMID- 18341099
TI  - Enterprise content and records management.

PMID- 18341100
TI  - Enterprise content management from the ground up.

PMID- 18341101
TI  - Clinical data exchange models. Matching HIE goals with IT foundations.

PMID- 18341102
TI  - Working without a paper net.

PMID- 18341103
TI  - Metadata, law, and the real world.

PMID- 18341104
TI  - Handling sensitive information in an NHIN.

PMID- 18341105
TI  - Understanding use cases.

PMID- 18341106
TI  - Transforming nursing through EHRs.

PMID- 18341107
TI  - Litigation response planning and policies for E-discovery.

PMID- 18341108
TI  - 2008 CPT coding update.

PMID- 18341109
TI  - Reducing outpatient billed as inpatient errors.

PMID- 18341110
TI  - Teaching the legal record.

PMID- 18341111
TI  - Effects of climate change on flux of nitrogen and carbon: air-land-freshwater
      marine links.

PMID- 18341112
TI  - Effect of climate change on flux of N and C: air-land-freshwater-marine links:
      synthesis.
AB  - Projected climate change might increase the deposition of nitrogen by about 10%
      to seminatural ecosystems in southern Norway. At Storgama, increased
      precipitation in the growing season increased the fluxes of total organic carbon
      (TOC) and total organic nitrogen (TON) in proportion to the water flux. In
      winter, soil temperatures near 0 degrees C, common under a snowpack, induced
      higher runoff of inorganic nitrogen (N) and lower runoff of TOC. By contrast,
      soil temperatures below freezing, caused by little snow accumulation (expected in
      a warmer world), reduced runoff of inorganic N, TON, and TOC. Long-term
      monitoring data showed that reduced snowpack can cause either decreased or
      increased N leaching, depending on interactions with N deposition, soil
      temperature regime, and winter discharge. Seasonal variation in TOC was mainly
      climatically controlled, whereas deposition of sulfate and nitrate (NO3)
      explained the long-term TOC increase. Upscaling to the river basin scale showed
      that the annual flux of NO3 will remain unchanged in response to climate change
      projections.

PMID- 18341113
TI  - Climate change impact on atmospheric nitrogen deposition in northwestern Europe:
      a model study.
AB  - A high-resolution chemical transport model, driven by meteorology representing
      current and future climate, was used to investigate the effects of possible
      future changes in climate on nitrogen deposition in northwestern Europe. The
      model system was able to resolve the climatology of precipitation and chemical
      properties observed in northern Europe during the 1980s, albeit with some
      underestimation of the temporal and spatial variability of meteorological
      parameters and chemical components. The results point toward a substantial
      increase (30% or more) in nitrogen deposition over western Norway as a
      consequence of increasing precipitation but more moderate changes for other
      areas. Deposition of oxidized nitrogen will increase more than the deposition of
      reduced nitrogen. Over Sweden, oxidized nitrogen will increase only marginally
      and reduced nitrogen will decrease, although annual precipitation is expected to
      increase here as well. This is probably because more reduced nitrogen will be
      removed further west in Scandinavia because of the strong increase in
      precipitation along the Norwegian coast. The total deposition of oxidized
      nitrogen over Norway is expected to increase from 96 Gg N y(-1) during the
      current climate to 107 Gg N y(-1) by 2100 due only to changes in climate. The
      corresponding values for Sweden are more modest, from 137 Gg N y(-1) to 139 Gg N
      y(-1).

PMID- 18341114
TI  - Natural variability in soil and runoff from small headwater catchments at
      Storgama, Norway.
AB  - To provide baseline data for climate manipulation experiments in 11 small (30-268
      m2) headwater catchments at Storgama, Telemark County, Southern Norway, we
      assessed the natural variability in site characteristics and runoff quality.
      Annual average concentrations in runoff at the sites have coefficients of
      variation between 26-61%, with the smallest values for total organic carbon (TOC)
      and carbon to nitrogen (C/N) ratios and the largest for inorganic nitrogen (N).
      The catchments have between two and five times higher concentrations of inorganic
      N, TOC, and total phosphorus than the larger (0.6 km2) Storgama watershed nearby.
      Concentrations of TOC and TON in runoff tend to increase with soil C and N
      content and with the volume of soil in the catchment. For nitrate (NO3) and
      ammonium in runoff, the reverse is true. In wet years the proportion of bare rock
      is a major predictor for the annual average NO3 concentration in runoff.

PMID- 18341115
TI  - Manipulation of snow in small headwater catchments at Storgama, Norway: effects
      on leaching of inorganic nitrogen.
AB  - We have manipulated the winter-time soil temperature regime of small headwater
      catchments in a montane heathland area of southern Norway to study the possible
      effects on concentrations and fluxes of inorganic nitrogen in runoff. The
      experiments included extra insulation of soils in two catchments to prevent
      subzero temperatures during winter, and removal of snow in two other catchments
      to promote soil frost. Increased soil temperatures during winter increased the
      springtime concentrations and fluxes of ammonium (NH4) and nitrate (NO3) in
      runoff. By contrast, snow removal with development of significant soil frost
      showed no systematic effects on mean concentrations or fluxes of inorganic N. The
      results from our experiments suggest that warmer soils during winter caused by
      exceptionally mild winters, or alternatively a heavy snowpack, imply a greater
      risk for inorganic N leaching in this region than a possible increase of soil
      frost events because of reduced snow cover.

PMID- 18341116
TI  - Manipulation of snow in small headwater catchments at Storgama, Norway: effects
      on leaching of total organic carbon and total organic nitrogen.
AB  - Projected increases in winter temperature due to future climate change may cause
      decreased snow accumulation at lower and intermediate altitudes in northern
      temperate regions. The resulting changes in soil temperature and water regime may
      affect the leaching of total organic carbon (TOC) and total organic nitrogen
      (TON). We manipulated the snow cover of small headwater catchments in a montane
      heathland area of southern Norway to quantify its effect on concentrations and
      fluxes of TOC and TON in runoff. Manipulations included snow removal, to promote
      soil frost, and insulation, to prevent soil frost. Snow removal resulted in
      increased TOC and TON concentrations, but decreased fluxes. Insulation caused a
      slight decrease in concentrations and fluxes of TOC. Our experiments show that a
      change in snow depth, and thus soil temperature, is not likely to have serious
      effects on TOC and TON leaching in the montane heathland area studied.

PMID- 18341117
TI  - Manipulation of precipitation in small headwater catchments at Storgama, Norway:
      effects on leaching of organic carbon and nitrogen species.
AB  - Projected changes in climate in Southern Norway include increases in summer and
      autumn precipitation. This may affect leaching of dissolved organic matter (DOM)
      from soils. Effects of experimentally added extra precipitation (10 mm week)
      during the growing season of 3 years (2004-2006) to small headwater catchments at
      Storgama (59 degrees 0'N, 550-600 m a.s.l.) on leaching of total organic carbon
      (TOC) and total organic nitrogen (TON) were assessed. Extra precipitation did not
      have a significant effect on average TOC and TON concentrations in runoff. Thus,
      fluxes of TOC and TON increased nearly proportionally with water fluxes. This
      suggests that a store of adsorbed and potentially mobile TOC and TON in catchment
      soils buffers the concentration of DOM in runoff. The size and dynamics of the
      pool of TOC and TON depends on the balance between production and leaching rates.
      Infrequent short droughts had only small effects on TOC and TON fluxes in runoff
      from the reference catchments.

PMID- 18341118
TI  - Projected stream water fluxes of NO3 and total organic carbon from the Storgama
      headwater catchment, Norway, under climate change and reduced acid deposition.
AB  - Fluctuations in the 20-year record of nitrate (NO3) and total organic carbon
      (TOC) concentrations and fluxes in runoff at the small headwater catchment
      Storgama, southern Norway, were related to climate and acid deposition. The long
      term decline in NO3 related to reduced NO3 deposition and increased winter
      discharge, whereas the long-term increase in TOC related to reduced sulfur
      deposition. Multiple regression models describing long-term trends and seasonal
      variability in these records were used to project future concentrations given
      scenarios of climate change and acid deposition. All scenarios indicated reduced
      NO3 fluxes and increased TOC fluxes; the largest projected changes for the period
      2071-2100 were -86% and +24%, respectively. Uncertainties are that the predicted
      future temperatures are considerably higher than the historical record. Also,
      nonlinear responses of ecosystem processes (nitrogen [N] mineralization) to
      temperature, N-enrichment of soils, and step-changes in environmental conditions
      may affect future leaching of carbon and N.

PMID- 18341119
TI  - Effect of climate change on fluxes of nitrogen from the Tovdal River basin,
      Norway, to adjoining marine areas.
AB  - The mass transport model TEOTIL was used to project nitrate (NO3) fluxes from the
      Tovdal River basin, southernmost Norway, given four scenarios of climate change.
      Forests, uplands, and open water currently account for 90% of the NO3 flux.
      Climate scenarios for 2071-2100 suggest increased temperature by 2-4 degrees C
      and precipitation by 3-11%. Climate experiments and long-term monitoring were
      used to estimate future rates of nitrogen (N) leaching. More water will run
      through the terrestrial catchments during the winter but less will run in the
      spring. The annual NO3 flux from the Tovdal River to the adjoining Topdalsfjord
      is projected to remain unchanged, but with more NO3 delivered in the winter and
      less in the spring. Algal blooms in coastal waters can be expected to occur
      earlier in the year. Major sources of uncertainty are in the long-term fate of N
      stored in soil organic matter and the impacts of forest management.

PMID- 18341120
TI  - Broken English, broken bones? Mechanisms linking language proficiency and
      occupational health in a Montreal garment factory.
AB  - Language barriers are often cited as a factor contributing to ethnic inequalities
      in occupational health; however, little information is available about the
      mechanisms at play. The authors describe the multiple ways in which language
      influences occupational health in a large garment factory employing many
      immigrants in Montreal. Between 2004 and 2006, individual, semi-structured
      interviews were conducted with 15 women and 10 men from 14 countries of birth.
      Interviews were conducted in French and English, Canada's official languages, as
      well as in non-official languages with the help of colleague-interpreters.
      Observation within the workplace was also carried out at various times during the
      project. The authors describe how proficiency in the official languages
      influences occupational health by affecting workers' ability to understand and
      communicate information, and supporting relationships that can affect work
      related health. They also describe workers' strategies to address communication
      barriers and discuss the implications of these strategies from an occupational
      health standpoint. Along with the longer-term objectives of integrating
      immigrants into the linguistic majority and addressing structural conditions that
      can affect health, policies and practices need to be put in place to protect the
      health and well-being of those who face language barriers in the short term.

PMID- 18341121
TI  - The right to vacation: an international perspective.
AB  - This report reviews international vacation and holiday laws and finds that the
      United States is the only advanced economy that does not guarantee its workers
      any paid vacation or holidays. As a result, one in four U.S. workers do not
      receive any paid vacation or paid holidays. The lack of paid vacation and paid
      holidays in the United States is particularly acute for lower-wage and part-time
      workers, and for employees of small businesses. This report also includes a
      comparative appendix with information on paid leave and holiday laws in
      Australia, Austria, Belgium, Canada, Denmark, Finland, France, Germany, Greece,
      Ireland, Italy, Japan, the Netherlands, New Zealand, Norway, Portugal, Spain,
      Sweden, Switzerland, and the United Kingdom.

PMID- 18341122
TI  - Increasing differential mortality by educational attainment in adults in the
      United States.
AB  - Economic inequality has increased substantially in the United States since the
      early 1970s. Inequality in mortality increased from 1960 to 1986. To assess the
      trend in inequality in mortality the authors calculate age-adjusted mortality
      rates by educational attainment for 2000 and compare them with rates from 1960
      and 1986, using relative and absolute indexes of inequality. Rates are calculated
      for non-Hispanic white and black adults aged 25 to 64 years, using mortality data
      from U.S. Vital Statistics and population estimates from the Census Public Use
      Microdata Sample. The trend toward increasing inequality in mortality between
      1960 and 1986 accelerated from 1986 to 2000. Improvements in mortality went
      disproportionately to those with the most education. Mortality rates for whites
      with low education, which declined from 1960 to 1986, actually rose from 1986 to
      2000. The relative change was greatest for those with only a high school
      education. This change, however, is largely explained by shifts in the
      distribution of education, which left those with a high school education in a
      lower position. The increase in inequality was particularly strong in whites and
      stronger in men than in women. For black men there was a small decline in
      absolute inequality between 1986 and 2000.

PMID- 18341123
TI  - Shaping public policy and population health in the United States: why is the
      public health community missing in action?
AB  - Renewed international interest in the structural determinants of health manifests
      itself in a focus on the social determinants of health and the public policy
      antecedents that shape their quality. This increased international interest in
      public policy in support of the structural determinants of health has had little
      traction in the United States. This should be surprising since the United States
      presents one of the worst population health profiles and public policy
      environments in support of health among wealthy developed nations. The U.S.
      position as a health status and policy outlier results from long-term
      institutional changes that are shaped by political, economic, and social forces.
      U.S. public health researchers' and workers' neglect of these structural and
      public policy issues conforms to the dominant ideological discourses that serve
      to justify these changes. The author presents some means by which public health
      researchers and workers can challenge these dominant discourses.

PMID- 18341124
TI  - Assessment of the FDA backgrounder on platinum in silicone breast implants:
      implications for public health policy.
AB  - A recent report by the U.S. Food and Drug Administration reviewed the literature
      on the subject of platinum in silicone gel-filled breast implants. In this study
      the author evaluates the FDA report for scientific accuracy and impartiality, and
      provides relevant discussions on financial conflicts of interest, an Institute of
      Medicine report, and public health policy. The study suggests that the FDA used
      discredited scientific practices in compiling its report. Reports by regulatory
      agencies should be scientifically accurate, with no partiality to industry. The
      current policy of one-way information flow from the FDA directly to those being
      informed needs to be revised. Greater importance should be placed on studies in
      which authors have no financial conflicts of interest.

PMID- 18341125
TI  - Minimum income protection and European integration: trends and levels of minimum
      benefits in comparative perspective, 1990-2005.
AB  - This article draws attention to the Europeanization of social policy and the
      development of minimum income protection in a large number of welfare
      democracies. The empirical analyses are based on unique institutional and
      comparative data on benefit levels from the Social Assistance and Minimum Income
      Protection Interim Dataset. There is some evidence of convergence in benefit
      levels among the European countries in the new millennium, but there is no clear
      proof of universal ambitions to fight poverty or of the existence of a single
      European social model. There are still welfare front-runners and those who lag
      behind in this regard, not only among industrial welfare democracies in general
      but also in Europe.

PMID- 18341126
TI  - Death in China: market reforms and health.
AB  - Has China's remarkable reduction in income poverty since 1980 been accompanied by
      comparable progress in health? The author's findings are fourfold. First,
      province-level rates of improvement in life expectancy (LE) were higher in the
      1990s than in the 1970s and 1980s, and were lowest in the 1980s. Second, even in
      the 1990s, when the province-level rates of improvement in LE were highest, they
      were lower than for many countries with similar initial LE level (although higher
      than the average for all such countries). Third, China's LE improvement between
      1980 and 2000 was achieved much more quickly by almost all other countries
      considered, and in particular by most lower-middle-income countries that had
      similar LE improvements; similar conclusions are drawn from an analysis of
      China's LE improvements relative to two other sets of comparator countries-
      selected presently rich countries and high-growth East Asian countries. Finally,
      even those Chinese provinces that performed best over the period experienced
      rates of improvement significantly lower than for comparator countries. China's
      experience of reducing health deprivations has been notably less impressive than
      its record of income poverty reduction. There is a need for China to invest in
      the redevelopment of its public health infrastructure, which has withered during
      the period of market-oriented reforms.

PMID- 18341127
TI  - Human genome epidemiology: reviewing the stakes.
AB  - Social science analysis of developments associated with the "new genetics," as
      the science moves from the laboratory into the policy arena, has focused
      primarily on the implications of numerous potential interventions and the
      introduction of data banks. The field continues to burgeon. This article
      interrogates the key assumptions of a newly emerging field, that of human genome
      epidemiology--a field that is yet to receive sustained attention from critical
      social theorists. Genome epidemiology, however, is the field of knowledge that is
      considered to be centrally important to mapping out the new directions for policy
      initiatives. The concern of this article is to "review the stakes." This involves
      pointing to and exploring the gap that has opened up between the advocates of an
      unproblematized rendition of a geneticized future and those critical of the basic
      problems accompanying its foundational concepts and dynamics. The work of Oyama
      is used to interrogate how this chasm is manifest when considering the domain of
      human genome epidemiology. The article explores the implications of such a
      critique at the level of the onto-epistemological assumptions of the accepted
      science of genetics, and the sociological concerns that emerge when these
      assumptions are extrapolated into the social research arena of epidemiology.

PMID- 18341128
TI  - The independence of international civil servants during the neoliberal decades:
      implications of the work stoppage involving 700 staff of the World Health
      Organization in November 2005.
AB  - The independence of international civil servants is critical to the fulfillment
      of their organizations' mandates, but it has been seriously undermined during 25
      years of neoliberal influence in U.N. agencies, including the World Health
      Organization. In November 2005, 700 staff at WHO headquarters participated in a
      one-hour work stoppage--the first industrial action in the organization's
      history. Hierarchical and arbitrary management, abuse of rules and procedures,
      nepotism and harassment, and undue influence of international financial
      institutions, powerful member states, and transnational corporations have
      exhausted morale and motivation, creating a conformist environment and
      interfering with technical health work. In the neoliberal era, WHO staff confront
      conflicting duties of loyalty to a handful of member states and their private
      interests and loyalty to WHO's constitutional mandate. International civil
      servants need support from governing bodies and from the world's people in
      finding the correct balance. A first essential step would be respect for
      international labor standards within the U.N. family and, in particular,
      negotiation status and collective bargaining--human rights in the workplace and
      prerequisites for staff independence, integrity, and competence, qualities
      required to serve the world's people.

PMID- 18341129
TI  - Is the unemployment rate in Sweden really 17 percent?
AB  - In 2006 the McKinsey Global Institute published an analysis of the Swedish
      economy, with the finding that the "de facto" unemployment rate in 2004 was 15 to
      17 percent, about three times higher than the official unemployment rate of 5.4
      percent. These estimates were cited in the media as part of critiques of recent
      Swedish economic performance. To arrive at the 15 to 17 percent "de facto"
      unemployment rate, McKinsey included "people who don't work, even though they
      should be able to" in the pool of the unemployed. The analysis reported here
      accepts the McKinsey methodology and applies it to the United States. The
      resulting "de facto" unemployment rate for the United States is 13.8 percent,
      compared with the 5.5 percent official U.S. unemployment rate, and the estimated
      15.5 percent "de facto" Swedish unemployment rate. If the two countries' prison
      and jail populations are also included in the "de facto" unemployment rate, the
      U.S. rate rises to 15.2 percent, just 0.5 percentage points lower than what
      McKinsey's equivalent figure would be for Sweden--15.7 percent.

PMID- 18341130
TI  - Diagnosis: Michael Moore--media paint filmmaker to be health care system's main
      problem.
AB  - The media reporting on Sicko, Michael Moore's documentary about the failures of
      the U.S. health care system, provides an example of how corporate media continue
      to twist and restrict the much-needed debate on health care reform. Aside from an
      occasional concession that having 46 million uninsured Americans is indeed
      problematic, the media's hype-filled conversation on health care avoids the
      issues and echoes old myths about the dangers of "government-run" and
      "socialized" health care. But in the face of the media demonization, universal
      health care is remarkably popular among the public.

PMID- 18341131
TI  - Bush aide blocked report: global health draft in 2006 rejected for not being
      political.
AB  - A surgeon general's report in 2006 that called on Americans to help tackle global
      health problems has been kept from the public by a Bush political appointee
      without any background or expertise in medicine or public health, chiefly because
      the report did not promote the administration's policy accomplishments. The
      report described the link between poverty and poor health, urged the U.S.
      government to help combat widespread diseases as a key aim of its foreign policy,
      and called on corporations to help improve health conditions in the countries
      where they operate.

PMID- 18341132
TI  - Coordination variability and skill development in expert triple jumpers.
AB  - The aim of this study was to examine the influence of skill of expert triple
      jumpers on the coordination variability of lower extremity intra-limb couplings.
      In contrast to the traditional motor learning perspective, we hypothesized that
      as skill and thus performance increases, movement coordination variability will
      also increase. Three-dimensional kinematic and ground reaction force data were
      collected during the hop-step transition phase of the triple jump. Relative
      motion plots and a modified vector coding technique were used to quantify the
      coordination variability across the trials. The results were consistent with a U
      shaped curve, representing coordination variability, as skill increases. The high
      coordination variability in less skilled athletes is present while the
      appropriate characteristics defining the movement coordination patterns are
      acquired. This coordination variability may not be beneficial to performance. As
      the refinement of these characteristics is achieved, coordination variability
      decreases, resulting in a more consistent or regulated performance. In the final
      stages of developing a skilled performance, a functional variability is accessed
      that brings flexibility to the system allowing it to cope with perturbations.
      This study highlights the need to address the learning effect when analysing
      coordination variability from a dynamical systems perspective.

PMID- 18341133
TI  - Biomechanical considerations of distance kicking in Australian Rules football.
AB  - Kicking for distance in Australian Rules football is an important skill. Here, I
      examine technical aspects that contribute to achieving maximal kick distance.
      Twenty-eight elite players kicked for distance while being videoed at 500 Hz. Two
      dimensional digitized data of nine body landmarks and the football were used to
      calculate kinematic parameters from kicking foot toe-off to the instant before
      ball contact. Longer kick distances were associated with greater foot speeds and
      shank angular velocities at ball contact, larger last step lengths, and greater
      distances from the ground when ball contact occurred. Foot speed, shank angular
      velocity, and ball position relative to the support foot at ball contact were
      included in the best regression predicting distance. A continuum of technique was
      evident among the kickers. At one end, kickers displayed relatively larger knee
      angular velocities and smaller thigh angular velocities at ball contact. At the
      other end, kickers produced relatively larger thigh angular velocities and
      smaller knee angular velocities at ball contact. To increase kicking distance,
      increasing foot speed and shank angular velocity at ball contact, increasing the
      last step length, and optimizing ball position relative to the ground and support
      foot are recommended.

PMID- 18341134
TI  - Canoe slalom competition analysis.
AB  - The aim of this study was to quantify the differences between groups of elite
      canoe slalom athletes based on the class they paddle in and the strategies they
      use in competition. Canoe and kayak footage was recorded using three cameras and
      analysed using lapsed-time time-motion analysis. Analysis was undertaken on the
      ten fastest competition runs for men's kayak and canoes and women's kayak for the
      22-gate semi-final/final course at the 2005 canoe slalom world championships.
      Comparison between the categories of paddlers revealed that despite canoe
      paddlers taking significantly (P < or = 0.05) fewer strokes than kayak paddlers,
      they were not significantly slower than men's single kayak paddlers with respect
      to their run times and only significantly slower between 4 of 22 gates. Results
      revealed also that paddlers using different turn strategies (spin vs. pivot) had
      significantly (P < or = 0.05) different split times for the gates before and
      after the execution of the manoeuvre. For a paddler this means that their
      individual strategy could be analysed and compared with those of others to
      determine if alternate strategies would be beneficial to their performance.

PMID- 18341135
TI  - Upper extremity kinematic trends of fly-casting: establishing the effects of line
      length.
AB  - Fly-fishing is a popular form of recreation. Recent evidence has associated
      overhand fly-casting movements with upper extremity pain. However, little
      research exists on the motions and coordination common to fly-casting. The aim of
      this study was to establish upper extremity kinematic trends of fly-casting while
      casting greater line lengths. It was hypothesized that kinematic casting
      parameters would increase and time between peak angular velocities would decrease
      with greater line length. Eighteen males participated in the study. Three
      dimensional motion capture was conducted to calculate shoulder, elbow, and wrist
      kinematics during casting conditions of 6.1, 12.2, 18.3, and 24.4 m of line.
      Multiple analyses of variance were used to assess the condition effect of line
      length on the kinematic variables (P = 0.05). Overall, total range of movement
      increased with increasing length of line cast. Peak angular velocity exhibited a
      proximal-to-distal trend: peak shoulder internal rotation followed by elbow
      extension, then wrist ulnar deviation. Time between peak shoulder and elbow
      angular velocities increased significantly as line length increased. Our findings
      indicate that specific changes in total range of movement accommodate the demands
      of casting greater lengths of line. Also, joint velocity coordination patterns of
      fly-casting appear to follow a proximal-to-distal pattern. These findings
      represent an initial foundation for connections between kinematics and upper
      extremity pain reported by fly-fisherman.

PMID- 18341136
TI  - The effects of differential and variable training on the quality parameters of a
      handball throw.
AB  - The aim of this study was to undertake a comprehensive temporal, effective, and
      practical training study (variable and differential learning) that would offer
      athletes the opportunity to increase their performance, and to analyse the
      effects by measuring kinematics and quality parameters. Two participants of
      differing standards--a player of the first Austrian League and an Olympic and
      World Champion--but of similar anthropometric characteristics were recruited. One
      of the participants (Austrian League) was tested on five different occasions (pre
      test and four retests) to measure the effects of four different training phases
      using kinematic analysis. The results of the study indicate an increase in ball
      velocity within the differential training phases (first, second, and fourth
      phases), different proximal-to-distal sequences of the participants, and a change
      of movement pattern during training measured by the segment velocities and the
      angle-time courses.

PMID- 18341137
TI  - Technique analysis of the kuda and sila serves in sepaktakraw.
AB  - The aims of this study were to gain insights on sepaktakraw serves, identify
      technique differences, and establish factors influencing ball speeds. The best
      successful kuda and sila serves of nine elite male national sepaktakraw players
      were captured using seven ProReflex 1000 optical cameras operating at 240 Hz. The
      kuda and sila serves are non-planar kicking techniques exhibiting a non proximal
      to-distal sequence. Differences in kicking kinematics (P < 0.05) signify
      differences between techniques. Compared with the sila, the kuda kicking limb is
      a longer rigid segment that moves over a greater range of motion. Together with a
      greater increase in foot and shank angular accelerations approaching ball
      contact, this leads to marginally higher kuda foot impact speeds. Since foot
      speeds were not at their peak during impact, a longer rigid kuda kicking limb was
      the primary determinant of kuda ball release speeds. Greater range of motion
      enables the longer rigid kuda lever to generate greater kicking angular momentum,
      resulting in greater impact impulse. This immediately translated to the
      significantly higher ball release speeds based on the impulse-momentum
      relationship. Coaching implications include improving hip joint flexibility and
      working on a fluid movement of a longer rigid segment kicking technique.

PMID- 18341138
TI  - An examination of slo-pitch pitching trajectories.
AB  - Many slo-pitch coaches and players believe that generating spin on a ball can
      affect its trajectory. The influence of air resistance on a ball that is thrown
      at a moderate speed and spin is unclear. The aim of this study was to examine the
      influence of spin on the ball's trajectory in slo-pitch pitching using both
      experimental results and ball flight simulations. Fourteen pitchers participated
      in the study, each of whom threw five backspin and topspin pitches each. Data
      were collected using standard three-dimensional videography. The horizontal
      velocity, vertical velocity, angular velocity, release height, and horizontal
      displacement of the backspin pitches were significantly higher than those of the
      topspin pitches. The ball flight simulations were developed to examine the
      influence of the ball spin, and it was concluded that the spin of the ball had a
      significant effect on the ball's vertical and horizontal displacements.
      Furthermore, our results suggest that a backspin pitch that reaches the maximum
      height allowable and lands in the front edge of the strike zone has the steepest
      slope. The present results add to our understanding of projectile motion and
      aerodynamics.

PMID- 18341139
TI  - Front- or rear-weighted track start or grab start: which is the best for female
      swimmers?
AB  - The aim of this study was to compare three competitive swimming starts (grab,
      rear-weighted track, and front-weighted track). The starts were compared in terms
      of time and instantaneous horizontal velocity, both at take-off from the block
      and at 5 m from the wall. Twenty US college female swimmers performed three
      trials of each of the three randomly ordered starts. Swimmers left the block
      significantly sooner using the front-weighted track start (0.80 s) than the other
      two starts (both 0.87 s; P < 0.001). In the rear-weighted track start, however,
      the athletes left the blocks with significantly higher horizontal velocity than
      in the grab or front-weighted track start (3.99 vs. 3.87 and 3.90 m/s,
      respectively; each P < 0.001). By 5 m, the front-weighted track start maintained
      its time advantage over the grab start (2.19 vs. 2.24s; P = 0.008) but not the
      rear-weighted track start (2.19 vs. 2.21 s; P = 0.336). However, the rear
      weighted track start had a significant advantage over the front-weighted track
      start in terms of instantaneous horizontal velocity at 5 m (2.25 vs. 2.18 m/s; P
      = 0.009). Therefore, the rear-weighted track start had a better combination of
      time and velocity than the front-weighted track start. There was also a trend for
      the rear-weighted track start to have higher velocity at 5 m than the grab start,
      although this did not reach statistical significance (2.25 vs. 2.20 m/s; P =
      0.042). Overall, these results favour the rear-weighted track start for female
      swimmers even though most of the athletes had little or no prior experience with
      it. Additional research is needed to determine whether males would respond
      similarly to females in these three different swimming starts.

PMID- 18341140
TI  - Biomechanics research in ski jumping, 1991-2006.
AB  - In this paper, I review biomechanics research in ski jumping with a specific
      focus on publications presented between 1991 and 2006 on performance enhancement,
      limiting factors of the take-off, specific training and conditioning,
      aerodynamics, and safety. The first section presents a brief description of ski
      jumping phases (in-run, take-off, early flight, stable flight, and landing)
      regarding the biomechanical and functional fundamentals. The most important and
      frequently used biomechanical methods in ski jumping (kinematics, ground reaction
      force analyses, muscle activation patterns, aerodynamics) are summarized in the
      second section. The third section focuses on ski jumping articles and research
      findings published after the establishment of the V-technique in 1991, as the
      introduction of this technique has had a major influence on performance
      enhancement, ski jumping regulations, and the construction of hill profiles. The
      final section proposes topics for future research in the biomechanics of ski
      jumping, including: take-off and early flight and the relative roles of vertical
      velocity and forward somersaulting angular momentum; optimal jumping patterns
      utilizing the capabilities of individual athletes; development of kinematic and
      kinetic feedback systems for hill jumps; comparisons of simulated and hill jumps;
      effect of equipment modifications on performance and safety enhancement.

PMID- 18341141
TI  - Can fast-twitch muscle fibres be selectively recruited during lengthening
      contractions? Review and applications to sport movements.
AB  - Literature examining the recruitment order of motor units during lengthening
      (eccentric) contractions was reviewed to determine if fast-twitch motor units can
      be active while lower threshold slow-twitch motor units are not active. Studies
      utilizing surface electromyogram (EMG) amplitude, single motor unit activity,
      spike amplitude-frequency analyses, EMG power spectrum, mechanomyographic, and
      phosphocreatine-to-creatine ratio (PCr/Cr) techniques were reviewed. Only single
      motor unit and PCr/Cr data were found to be suitable to address the goals of this
      review. Nine of ten single motor unit studies, examining joint movement
      velocities up to 225 degrees/s and forces up to 53% of a maximum voluntary
      contraction, found that the size principle of motor unit recruitment applied
      during lengthening contractions. Deviation from the size principle was
      demonstrated by one study examining movements within a small range of low
      velocities and modest forces, although other studies examining similar low forces
      and lengthening velocities reported size-ordered recruitment. The PCr/Cr data
      demonstrated the activation of all fibre types in lengthening maximal
      contractions. Most evidence indicates that for lengthening contractions of a wide
      range of efforts and speeds, fast-twitch muscle fibres cannot be selectively
      recruited without activity of the slow-twitch fibres of the same muscle.

PMID- 18341142
TI  - Kinetics of struvite precipitation: effect of the magnesium dose on induction
      times and precipitation rates.
AB  - The presence of white deposits in specific areas of wastewater treatment plants
      is generally the consequence of the spontaneous formation of a mineral called
      struvite. Struvite forms when the levels of phosphate, ammonium and magnesium
      naturally available in wastewater effluents reach a minimum molar ratio 1:1:1
      under specific conditions of pH, temperature and mixing energy. Originally
      regarded as a phenomenon to be controlled or eliminated, struvite has been lately
      identified as an alternative way of removing and recovering P from wastewater
      effluents and generating a product identified as an excellent base for the
      production of slow release fertilisers. Chemical and physical principles of
      struvite precipitation and the development of crystallisation technologies have
      been widely investigated. However, little interest has been given to kinetics of
      struvite precipitation. In the present work the kinetics of struvite formation
      have been investigated at both laboratory and pilot scale in synthetic solutions
      containing Mg(2+), NH4(+), and PO4(3-) ions in a molar ratio 1:2:2 at room
      temperature. These different tests have used pH measurements to assess the impact
      of water chemistry on induction times, and more precisely the influence of
      magnesium levels on kinetic rates. Experimental results and kinetic calculations
      revealed that the control of the magnesium dose initially present in solution is
      decisive of the speed at which struvite nucleates.

PMID- 18341143
TI  - Comparison of textile dye treatment by biosorption and membrane bioreactor.
AB  - The Cassulfon CMR is a sulphuric textile dye mainly used to colour "jeans". It
      has a dark black-blue colour, with high intensity of colour and high mineral
      compounds (71% of dry matter). Direct filtration experiments were carried out to
      quantity the capacity of macro porous membranes (1.2, 0.2 or 0.1 microm) to
      separate organic matter and colour from the effluent. The results show that no
      direct membrane filtration was efficient. To evaluate the capacity of a
      biological way for the elimination of this dye, batch experiments were performed
      to quantify the dye sorption capacity on activated sludge. Results show the high
      capacity of the biomass to adsorb colour (more than 4gCOD gMLVSS(-1)) while 15%
      of COD remain in the soluble fraction. To evaluate the biodegradability potential
      of the sludge, continuous operations were carried out in a membrane bioreactor
      (MBR). Results confirm the very high MBR potential to treat such dye effluents.
      During operations, the organic load was progressively increased from 0.33 to 1.33
      kg m(-3) d(-1) and the permeate quality was always free of suspended solids or
      turbidity. Moreover, the permeate COD values were always lower than 60 mg l(-1)
      and small permeate coloration only appeared during malfunctioning periods.

PMID- 18341144
TI  - A comparative study of five horizontal subsurface flow constructed wetlands using
      different plant species for domestic wastewater treatment.
AB  - This project studied domestic wastewater treatment by horizontal subsurface flow
      (HSSF) constructed wetlands (CW) and compared the effect of four different plant
      species on the operating conditions, dissolved oxygen (DO), and redox potential
      (ORP), and their efficiency on pollutants removal. Five HSSF CWs were fed for 10
      months with low loaded synthetic domestic wastewater, using theoretical hydraulic
      residence time of 7.6 days. The plant species under study were the following:
      Phragmites australis (CW1), Lythrum salicaria (CW3), Cladium mariscus (CW4) and
      Iris pseudacorus (CW5). CW2 was not planted and this was used as control.
      Qualitative measurements determined a greater growth of Lythrum salicaria and
      Iris pseudacorus than the others. Dissolved oxygen concentrations were very low
      in the entire bulk liquid of all the CWs. Also ORP values were very similar in
      all wetlands, dealing with facultative anaerobic environments. All planted
      wetlands improved pollutants removal compared with the unplanted control wetland.
      The performances in terms of COD, TN, TP and SO4(2-) removal obtained by the
      different CWs were in the ranges 80-90%, 35-55%, 15-40% and 45-60% respectively.
      Lythrum salicaria and Iris pseudacorus, which exhibited greater growth, were
      always the most efficient species that improved not only nutrients plant uptake
      but also other microbial removal processes probably due to a higher aeration
      potential, such as nitrification or aerobic respiration. Sulphate reduction was
      the most important mechanism for COD removal. Cladium mariscus, an autochthonous
      plant that grows in the south-central Iberian Peninsula, was less efficient than
      Lythrum salicaria and Iris pseudacorus, but improved the unplanted wetland
      wastewater efficiency.

PMID- 18341146
TI  - Antibacterial effects of chitosan powder: mechanisms of action.
AB  - Chitosan, the deacetylated derivative of chitin, is a natural D-glucosamine
      polymer that can be extracted from the shells of seafood such as prawns crabs and
      lobsters. It can be used as a flocculent, plant disease resistant promoter, anti
      cancer agent, wound healing promotion agent and antimicrobial agent. The aim of
      this paper is the study of the interaction between chitosan powder and various
      kinds of pathogen microorganisms potentially present in water. First of all,
      physico-chemical characterisations of chitin and chitosan powder were performed.
      The deacetylation yields were 35%, 60% and 80 +/- 10%. The experimental studies
      focused on the measurements of the mortality constant rate for various bacterial
      strains, Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis and
      Staphylococcus saprophyticus. An explanation of the antibacterial mechanisms is
      proposed involving the cell wall disruption due to free amino groups present in
      chitosan.

PMID- 18341145
TI  - Treatment of surfactant stabilized oil-in-water emulsions by means of chemical
      oxidation and coagulation.
AB  - The model wastewater samples investigated in the current study represented oil-in
      water (O/W) emulsions with small oil (diesel/black oil) and high surfactant
      (Anrol/Decon90) concentrations generated during washing of oil tankers or tank
      wagons. Coagulation with aluminium sulphate, ferric chloride and lime milk, and
      chemical oxidation by hydrogen peroxide catalyzed ferrous ions were applied as
      traditional and advanced treatment processes, respectively. Coagulation proved
      more feasible for oil content removal than for COD reduction. Both COD and oil
      content removal, were higher if Anrol was used as a surface active agent. The
      comparison of wastewater samples with different oil products but the same
      detergent showed more effective black oil removal. Coagulation was found
      ineffective as a pre-treatment technology for biodegradability improvement and
      toxicity reduction in surfactant stabilized O/W emulsion wastewater samples. The
      application of Fenton chemistry showed significant COD, UV absorbance and BOD
      removal, but no improvement in wastewater samples biodegradability. The maximum
      COD reduction and oil content removal from wastewater samples was above 90%. The
      oxidation of wastewater containing Decon90 required higher dosages of the Fenton
      reagent than wastewater with Anrol. Both Anrol and Decon90 contaminated
      wastewater samples were found to be detoxified even after moderate hydrogen
      peroxide dosages had been applied in the oxidation step.

PMID- 18341147
TI  - Influence of complex fibrous media composition on their performances for VOC and
      particle removal.
AB  - Amongst atmospheric pollutants, two major types can be distinguished: airborne
      particles such as dust, and gaseous compounds such as Volatile Organic Compounds
      (VOCs). Fibrous filters are commonly used to remove particles while activated
      carbon beds trap VOCs. In order to obtain a single-stage device as efficient at
      collecting particles with a size less than 10 microm (PM10) as removing VOCs,
      prototype fibrous media containing activated carbon fibers (ACF) associated with
      cellulose fibers (CF), which are non-adsorptive, have been developed. The
      influence of ACF ratio and the degree of beating of CF on porous structure,
      mechanical strength and treatment performances of the medium was studied.
      Experimental results show that an increase in ACF mass ratio increases the inter
      fiber porosity and overall adsorption capacity (the intrinsic adsorption capacity
      of ACF remains constant whatever the composition), but decreases the mechanical
      strength and particle collection efficiency of the medium. Moreover, an increase
      in the beating of CF enhances the mechanical strength of the medium and its
      particle collection efficiency, but decreases its porosity and has no effect on
      adsorption capacity. Consequently, a medium containing 50% ACF associated with CF
      with a low degree of beating (16 degrees SR) presents the best performance for
      combined filtration.

PMID- 18341148
TI  - Assessment of capillary suction time (CST) test methodologies.
AB  - The capillary suction time (CST) test is a commonly used method to measure the
      filterability and the easiness of removing moisture from slurry and sludge in
      numerous environmental and industrial applications. This study assessed several
      novel alterations of both the test methodology and the current standard capillary
      suction time (CST) apparatus. Twelve different papers including the standard
      Whatman No. 17 chromatographic paper were tested. The tests were run using four
      different types of sludge including a synthetic sludge, which was specifically
      developed for benchmarking purposes. The standard apparatus was altered by the
      introduction of a novel rectangular funnel instead of a standard circular one. A
      stirrer was also introduced to solve the problem of test inconsistency (e.g. high
      CST variability) particularly for heavy types of sludge. Results showed that
      several alternative papers, which are cheaper than the standard paper, can be
      used to estimate CST values accurately, and that the test repeatability can be
      improved in many cases and for different types of sludge. The introduction of the
      rectangular funnel demonstrated an obvious enhancement of test repeatability. The
      use of a stirrer to avoid sedimentation of heavy sludge did not have
      statistically significant impact on the CST values or the corresponding data
      variability. The application of synthetic sludge can support the testing of
      experimental methodologies and should be used for subsequent benchmarking
      purposes.

PMID- 18341149
TI  - Developmental study of a low-pH magnesium phosphate cement for environmental
      applications.
AB  - This paper presents a laboratory investigation into the development of a low-pH
      magnesium phosphate-based cement for use in in-situ stabilisation/solidification
      systems, as a more effective alternative to Portland cement. The idea is to
      develop a cement-based binder with a low enough pH to facilitate biodegradation
      in combination with stabilisation/solidification processes. Potassium dihydrogen
      orthophosphate was selected as the phosphate source, dead-burned magnesia as the
      magnesium source and boric acid as the retarder. The range of mixes were tested
      primarily on their pH development which was found to be in the range of 6-9.5 for
      a magnesia to phosphate ratio range of 1:1 to 1:5. The testing revealed a dense
      microstructure, high early-age strength development and low volume expansion of
      the developed cement. Observed fracturing of some of the cured cement samples has
      been related to the curing conditions and the impurities present in the magnesia.
      On the basis of microstructural examination, observed white crystalline deposits
      on cured samples are likely to be a reaction product of magnesia and potassium
      dihydrogen phosphate.

PMID- 18341150
TI  - Heavy metal and phosphorus content of fractions from manure treatment and
      incineration.
AB  - Alternative uses of pig manure are being considered, including separation and
      eventual incineration of the solid fraction to produce energy and ash. The
      efficiency of a screw press, a decanting centrifuge and chemical treatment in
      transferring N, P and heavy metals from slurry to a solid fraction were compared.
      Chemical treatment by coagulants and flocculants removed heavy metals most
      efficiently; they were transferred to the solid fraction in the order Zn > Cu >
      Cd by all three types of equipment. With centrifugation the heavy metal load on
      land where the solid fraction was applied was very low, whereas on land where the
      liquid fraction was applied it was only slightly less than that from un-separated
      manure. Conversely, chemical treatment resulted in a heavy metal load similar to
      that from un-separated manure with the solid fraction, while with the liquid
      fraction it was reduced to 20% of that from un-separated manure. Incineration of
      the solid fraction produces bottom ash and fly ash containing high levels of P.
      Most of the P and less than 10% of Cd is present in the bottom ash, producing an
      ash low in Cd content and a fly ash high in Cd. However, Cu and Ni tend to
      accumulate in the bottom ash. Chemical extraction procedures revealed that P
      availability was high in all liquid and solid fractions except the bottom ash
      from incineration where approximately 80% of the P was transformed into a form of
      apatite. Since more bottom ash than fly ash is being formed, significant amounts
      of P may be immobilized by incineration of solid fractions.

PMID- 18341151
TI  - The effect of silver ions and chlorine on the survival of Staphylococcus aureus
      and Bacillus cereus in dishwater.
AB  - This paper investigates the effect of chlorine and silver ion solutions on the
      survival of Bacillus cereus (vegetative phase) and Staphylococcus aureus in batch
      cultures, representing dishwater. Dishwater contains organic matter and bacteria
      and bacterial activities are partly reduced by high pH (11-12) and temperature
      (55-65 degrees C) in professional and domestic dishwashers. In manual
      dishwashing, temperature and pH are kept lower (45 degrees C and pH 7), which is
      less sufficient for the reduction of bacteria. In a broth, organic loaded in
      order to mimic dishwater, solutions of Ag or hypochlorite were added at 45
      degrees C and pH 7 and samples were withdrawn for a period of 40 minutes. 1 ppm
      Ag+ was required to obtain a 1 to 2 log unit reduction of B. cereus and S. aureus
      in 10 minutes. An addition of 160 ppm hypochlorite reduced B. cereus and S.
      aureus by 4 log units in two minutes, whereas 16 ppm of hypochlorite had no
      effect on the survival of S. aureus. The level of free residual chlorine varied
      with the COD value of the cultured solutions. We found that both silver and
      hypochlorite can be used as antibacterial agents in dishwater. The disadvantage
      with the use of hypochlorite is that the COD value determines the antibacterial
      effect. Using Ag+ solutions to reduce bacteria has the drawback that they are
      toxic to water-living organisms and are considered to develop Ag+ resistant
      bacteria. To reduce the risk of cross-contamination from dishwater to dishware
      high temperature and detergent with high pH is to be preferred.

PMID- 18341152
TI  - What makes a legal system effective?

PMID- 18341153
TI  - Coke v. Bumble--comments on some aspects of unlawful killing and its disposal.
AB  - The publication of the Law Commission's Consultation Paper and final proposals
      for the reform of homicide legislation has prompted the author to review some
      clinical and legal aspects of homicidal behaviour. It is suggested that the
      complexities of this behaviour are not well served under current legal
      provisions.

PMID- 18341154
TI  - A tale of two cities: a review of homicide in Melbourne and Glasgow in 2005.
AB  - The Departments of Forensic Medicine and Science at the University of Glasgow and
      the Victorian Institute of Forensic Medicine in Melbourne are academic university
      based forensic medicine units providing a medico-legal death investigation
      service to the Strathclyde region of Scotland and the State of Victoria,
      Australia, respectively. We reviewed and compared homicides in the two
      jurisdictions for the year 2005. Whilst gross numbers were comparable, the
      homicide rate per capita was significantly higher in Glasgow. Death due to
      stabbing comprised a greater proportion of homicides in Glasgow, reflective of a
      well recognised social epidemic of knife-related trauma amongst young males.
      Blunt force trauma was the most prevalent cause of homicidal injury in the
      Australian cases. The cities shared a low incidence of firearm- related homicide,
      reflective of strict legislative initiatives.

PMID- 18341155
TI  - Offending in the learning disabled population: a retrospective audit of Tayside
      learning disability service court reports.
AB  - The literature regarding offending in the learning disabled population is
      limited; the effects of normalisation and deinstitutionalisation on offending
      behaviour is not yet determined. We retrospectively examined 93 court reports
      completed by the Tayside learning disability service since 1986. Twenty patients
      were not considered to be learning disabled. Sixty-four of the subjects deemed
      learning disabled faced charges, the most common being public order offences,
      which was in common with previous reports. Eighteen per cent of these had a co
      morbid mental illness, the majority attracting a diagnosis of schizophrenia.
      Inpatient assessment, assessment as a day patient or probation were recommended
      for about two-thirds. Fewer than 50% of cases had no psychiatric recommendation
      made to the court. There was a predominance of arson and sexual offending.
      Arsonists were twice as likely as sex offenders to be recommended for inpatient
      treatment.

PMID- 18341156
TI  - Hospital bed related fatalities: a review.
AB  - All medico-legal cases of unexpected death during hospitalisation or
      accommodation in rest or nursing homes, which were investigated at the Department
      of Forensic Medicine during a 30-year-period, have been reviewed. In the majority
      of cases, the fatal outcome was bedrail or restraint related, but falls out of
      bed or from a patient hoist lift can also trigger a death. As expected, the
      manner of death was mainly accidental. In about 70% of cases, mechanical asphyxia
      (such as smothering and thoraco-abdominal compression) was substantiated as the
      mechanism of death. A substantial number of the patients had important medical
      antecedents, such as cognitive impairment due to cerebro-vascular accidents. In
      about half of the cases, human negligence was clearly related to the event
      whereas in only 15% of cases was there a technical mistake. We believe that some
      sudden and unexpected fatalities, due to physical restraint or other devices
      (such as a patient hoist lift), are under-reported because of the medico-legal
      implications. However, reporting such events could induce better precautions and
      prevent recurrences. Therefore, this study may be important not only for forensic
      pathologists, but also for a larger group of social workers.

PMID- 18341157
TI  - A comparison of external and internal injuries within an autopsy series.
AB  - The relationship between external injuries and internal injuries was
      investigated, with the aim of determining whether potentially lethal internal
      injuries could be reliably inferred from external findings alone. From a database
      of post-mortem reports, 291 were extracted and examined. The external and
      internal injuries were coded according to region, type and severity. Analysis of
      the data consisted of Spearman correlations for severity and positive predictive
      values for internal injuries of high lethality. Overall, the correlation between
      external and internal injuries was poor. The most predictive external injuries
      were multiple lacerations, large abrasions with lacerations, and gross
      distortions. Predictably, the most severe external injuries were the most
      reliable predictors of lethal internal injuries. External injuries of the head
      were more predictive of internal damage than external injuries elsewhere. Minor
      external injuries (such as bruises, small abrasions or small lacerations) did not
      predict lethal internal injuries. In conclusion, external examination findings
      are largely unreliable as markers of lethal internal injuries in the forensic
      investigation of victims of motor vehicle trauma, especially in situations where
      the external injuries are minor. Further research into non-invasive methods of
      forensic investigation is warranted.

PMID- 18341158
TI  - Sections 37/41 Mental Health Act 1983: a study of judges' practice and assessment
      of risk to the public.
AB  - Previous studies have reported that a significant proportion of forensic
      psychiatrists have had experience of restriction orders being made contrary to
      medical recommendations. Judges were interviewed to ascertain their experiences,
      sentencing practice and the factors taken into consideration when determining
      whether or not to attach a restriction order. In particular, the reasons why a
      restriction order might be made contrary to medical opinion were explored. Twelve
      judges sitting in crown courts in England were interviewed. The interviewees were
      unanimous in their view that where a hospital order was being considered
      involving a serious offence a psychiatrist should take a firm view on whether a
      restriction order was also required. Furthermore, the interviewees stated that
      they would anticipate a positive recommendation from psychiatrists in cases
      involving homicide, arson and serious sexual and violent offences. Demographic
      factors, including ethnicity, were irrelevant in their deliberations. The
      experience of this sample is that restriction orders are rarely made contrary to
      medical recommendations and in the rare circumstances they are made, insufficient
      emphasis has been placed on previous offending behaviours or the issue of public
      protection. In addition to the primary intention to protect the public nearly
      half the sample stated that an additional intention was to ensure compliance with
      both after-care services and medication.

PMID- 18341159
TI  - Sudden death while driving a four-wheeled vehicle: an autopsy analysis.
AB  - We retrospectively analysed forensic autopsies to resolve various issues
      associated with sudden natural death while driving. We collected information
      about the medical history, drug treatment, anthropometry and body mass index
      (BMI) of 34 individuals who suddenly died of natural causes while driving four
      wheeled vehicles. The reasons for driving, details of the vehicle, type of
      collision, perspective of vehicle behaviour and types of avoidance manoeuvres
      were also examined. The injury severity score (ISS), the Abbreviated Injury Scale
      (AIS) and the degree of cardiomegaly of the driver were determined from autopsy
      findings. The dominant cause of death was ischemic heart disease, which closely
      agreed with previous findings. However, forensic signs indicated that only 20.6%
      of deceased drivers had attempted avoidance manoeuvres such as braking or
      steering before the fatal accident, which contradicts previous findings.

PMID- 18341160
TI  - Section 5(2) MHA 1983: results of a three-year rapid cycle clinical audit.
AB  - The aim of this paper was to establish whether section 5(2) of the Mental Health
      Act 1983 was being used appropriately in an inpatient psychiatric unit in the UK.
      A clinical audit was conducted over three consecutive years. Peer review of
      decisions to use section 5(2) on the hospital's adult and old age wards was
      conducted by junior medical staff. Ninety-eight per cent of the uses of section
      5(2) were felt to be appropriate and most were reviewed within 72 hours. Very few
      patients (5%) were placed on this section again during their admission. The
      number placed on section 5(4) prior to section 5(2) increased from 2% to 12%. The
      proportion reviewed within the first 24 hours of detention nearly doubled over
      the audit period and fewer patients subsequently went on to sections 2 or 3 by
      the third year. There was no evidence of inappropriate use of section 5(2).
      Changes in the shift system for junior medical staff may have inadvertently led
      to a more frequent use of section 5(4). The use of further formal detention after
      section 5(2) declined, although this decline was not statistically significant.

PMID- 18341161
TI  - Trivial trauma, heart disease and medico-legal interpretation of death.
AB  - Forensic experts are often required to give an opinion on the cause of death and
      its medico-legal interpretation in cases where an individual dies after receiving
      non-fatal injuries and at autopsy is discovered to have had a natural disease
      that alone could have caused death. The significance of this varies in different
      countries depending on the local laws relating to death in cases of trivial
      trauma associated with natural disease. This paper discusses this issue from an
      Indian perspective with the help of an illustrative case report and highlights
      the importance of the forensic pathologist in such cases.

PMID- 18341162
TI  - A devastating case of purpura fulminans in a young adult seven years after a
      splenectomy: a case report.
AB  - It is well known that asplenic patients can suffer immediate and long-term
      infective sequelae, most of all from capsulated bacteria, whereas appropriate
      immunization can reduce the incidence of postsplenectomy sepsis. We discuss the
      case of a young adult developing an overwhelming post-splenectomy sepsis (OPSS)
      due to streptococcus pneumoniae seven years after the splenectomy for a traumatic
      injury. Neither immunoprophylaxis nor antibiotic therapy, whose value is
      underlined by literature data and international guidelines, was ever
      administered, either by the hospital physicians or by the general practitioner.

PMID- 18341163
TI  - Fast eating syndrome: a case report.
AB  - Choking while consuming food is a cause of death that has long been known and
      studied. Such deaths were popularly known as 'cafe coronary deaths', which
      denoted a fatal occlusion of the upper airway by food substances. The event
      commonly occurs while also consuming large quantities of ethyl alcohol or drugs,
      or in a psychiatric patient. Here, we present a case of an individual who choked
      to death while on duty and the main reason for choking was his eating habit which
      deviated from the known common causes of choking. We also discuss some causes of
      choking in elderly individuals.

PMID- 18341164
TI  - The use of multiple exostoses in the identification of incinerated human remains:
      a case report.
AB  - A case of roentgenographic medical identification of an incinerated deceased
      sixteen-year-old male is reported. Comparison of ante-mortem and post-mortem
      radiographs of the fibula, tibia and femur for purposes of identification was
      based on the deceased person's recent radiographic medical history, recorded less
      than two months prior to the death, with a diagnosis of multiple exostoses.
      Radiographic evaluation of the anatomic variants of the lower limb bones
      associated with this neoplastic process provided a positive identification in a
      visually unidentifiable person with no antemortem dental records, and an
      inability to fingerprint due to soft tissue destruction.

PMID- 18341165
TI  - Decapitation with egg shelling of the skull in a road traffic accident: a case
      report.
AB  - A 40-year-old lady was found dead on a road early one morning. She had allegedly
      been run over by a speeding vehicle. The head of the deceased had been
      decapitated, with egg shelling of the skull from the scalp and face. The skull
      was lying a little distance away from the rest of the body. Although decapitation
      is not an unknown entity in a road traffic accident, subsequent egg shelling of
      the skull, leaving behind scalp and face tissue, has not been reported in a road
      traffic accident in the forensic literature.

PMID- 18341166
TI  - Elderly and depression.
AB  - It is believed that it is 'normal' for the elderly per sons to become depressed
      and many cases aren't recognized and thus lead to untold misery for the sufferers
      and their families. We have found that majority of the clients under study were
      females belonging to low socio economic status, uneducated and unemployed.
      Majority of the clients had moderate depression (58%), And about 19% of them had
      severe depression. The problems related to subjective depressive feelings were
      investigated through a structured questionnaire surveyed among 100 elderly
      clients in Udhyava Village of Udupi district. We conclude that there is a
      significant relationship between family--friend relationships and depressive
      feelings of aged people.

PMID- 18341167
TI  - Importance of play for hospitalized children.

PMID- 18341168
TI  - Community health nurse in disaster management.

PMID- 18341169
TI  - Attitude towards nursing profession.

PMID- 18341170
TI  - Effectiveness of structured teaching on home care management of diabetes
      mellitus.

PMID- 18341171
TI  - Nurses' knowledge of their legal responsibilities towards patient care.

PMID- 18341172
TI  - Human development and the legacy of women.

PMID- 18341173
TI  - Health, poverty and development.

PMID- 18341174
TI  - Community-based initiatives and their relation to poverty reduction and health
      development: experiences in the Eastern Mediterranean region.

PMID- 18341175
TI  - The role of health promotion in poverty reduction.

PMID- 18341176
TI  - Seroprevalence of hepatitis A among children of different socioeconomic status in
      Cairo.
AB  - To determine seroprevalence of anti-hepatitis A virus (HAV) antibodies and
      potential risk factors for and age of contracting symptomatic hepatitis A
      infection among children of different socioeconomic status (SES) in Cairo, we
      carried out a cross-sectional study on 426 children aged 3-18 years from low SES
      areas and 142 from high SES areas. Seroprevalence was significantly higher with
      age. Seropositivity to anti-HAV antibodies was significantly higher among
      children of low and very low SES, 90%, compared to children of high SES, 50%.
      Water supply and sewage disposal were the most significant risk factors for HAV
      seropositivity in children of low SES. Children of high SES were more likely to
      be vulnerable to infection in adolescence than those of low SES.

PMID- 18341177
TI  - Breast cancer risk factors in south of Islamic Republic of Iran: a case-control
      study.
AB  - A case-control study was carried out from April 2000 to March 2002 to investigate
      risk factors for breast cancer in Bandar Abbas, south Islamic Republic of Iran.
      Using logistic regression analysis, 168 women with pathologically confirmed
      primary breast cancer were compared with 504 age-matched controls. Significant
      risk factors were: family history of breast cancer in a first-degree relative,
      younger age at menarche, never married, first full-term pregnancy age 30+ years
      and >5 full-term pregnancies. In multivariate analysis, negative history of
      breastfeeding was also significant. Cases and controls did not differ with regard
      to parity, history of abortion, oral contraceptive use, menopausal status, age at
      menopause, ever-use of hormone replacement therapy, history of benign breast
      disease or history of cigarette smoking.

PMID- 18341178
TI  - [Pilot study of antiretroviral therapy in Djibouti].
AB  - A cross-sectional survey was conducted among 112 HIV positive patients who had
      received antiretroviral therapy for >3 months to assess the efficacy of treatment
      (viral load <400 copies/mL). The median age at enrolment was 36 years, 90% of
      patients were at the AIDS stage and median CD4 rate was 118/mm3. Patients
      received a combined treatment of 2 NRTI +1 NNRTI (51%), 3 NRTI (45%) and 2 NRTI+1
      PI (4%). Virological efficacy was seen in 74% of the patients, irrespective of
      the prescribed protocol and the initial clinical and immunological profile. Mean
      improvements measured were 20% on the Karnofsky index (KI), 2.1 kg/m2 in body
      mass index and 82 cells/mm in CD4. The prevalence of side effects was 84%. The
      predictors for treatment success were quality of care and KI > 70%.

PMID- 18341179
TI  - [Evaluation of compliance with antiretroviral treatment in a cohort of 200
      patients in Djibouti, 2005].
AB  - We determined the rate of compliance with antiretroviral therapy and investigated
      the factors that influence it among 86 HIV patients. Compliance ratio (number of
      tablets taken/number prescribed) was assessed by tablet count. The mean ratio of
      compliance was 92%. By tablet count, 77% of the patients were compliant
      (compliance ratio > or =90%). Non-compliance was significantly associated with
      side-effects, degree of confidentiality of the care centre and travelling.
      Compliance correlated significantly with viral load. In multivariate analysis,
      community support and level of education protected against non-compliance.
      Patients having already missed a dose and those dissatisfied with confidentiality
      had a 4 times greater risk of non-compliance.

PMID- 18341180
TI  - Economic cost of malaria on households during a transmission season in Khartoum
      State, Sudan.
AB  - This study was conducted in 2004 among 1200 households in Khartoum to estimate
      the direct and indirect economic costs of malaria for households. Information on
      the household and the malaria episodes was collected (care-seeking behaviour,
      working days lost and expenditure on malaria treatment). There were 327 episodes
      of malaria; 25.2% of the households reported at least 1 malaria episode during
      the month preceding the survey. In only 18.0% of malaria episodes was the
      individual economically active. The average treatment expenditure per fully cured
      case was US$ 6.3 (SD 5.9). The average indirect cost per fully cured case was
      U.S. $3.2 (SD 9.2); it was higher for individuals working in the informal sector
      than those employed in the formal sector.

PMID- 18341181
TI  - Incidence and risk factors of neonatal hypothermia at referral hospitals in
      Tehran, Islamic Republic of Iran.
AB  - To identify the incidence rate and risk factors of neonatal hypothermia at
      referral hospitals in Tehran, Islamic Republic of Iran, 900 neonates were
      randomly selected. Body temperature was measured repeatedly at different time
      points after birth. More than 50% became hypothermic soon after birth. Multiple
      regression analysis showed that low birth weight, low gestational age
      environmental temperature, low Apgar score, multiple pregnancy and receiving
      cardiopulmonary resuscitation were significantly associated with hypothermia.
      These findings suggested that there is an urgent need to sensitize and educate
      all levels of staff dealing with neonates in our country.

PMID- 18341182
TI  - BDN programmes and the effect of medical students' interventions to promote child
      health in Sudan.
AB  - Basic development needs (BDN) is an approach to community development that aims
      at improving quality of life through the full involvement and self-management of
      communities, supported by intersectoral collaboration. The objective of this
      study was to assess the effects of BDN implementation in an area of Sudan on
      aspects of a programme implemented by students from the Faculty of Medicine,
      University of Gezira. The study revealed that the joint implementation of BDN
      programmes and students' interventions brought about marked improvement of family
      and community practices as well as greater reduction in the incidence of all
      assessed major childhood illnesses (diarrhoea, cough and fever) than when the
      students' programme was implemented alone. BDN implementation also facilitated
      the retrieval of good quality community-based data.

PMID- 18341183
TI  - Influence of parental and socioeconomic factors on stunting in children under 5
      years in Egypt.
AB  - We assessed the relationship between parental and socioeconomic characteristics
      and nutritional status of children under 5 years in Egypt. Data from the 2000
      Egypt Demographic and Health Survey were used. A logistic regression technique
      was used to estimate the odds of being malnourished. Children whose mothers had a
      higher level of education and were >150 cm had a lower risk of stunting than
      those of mothers with no education and shorter height (<150 cm). Parental
      consanguinity, rural residence, high birth order and short birth interval
      significantly increased the odds of stunting. Children aged > 12 months had
      greater odds of stunting than those <12 months.

PMID- 18341184
TI  - Maternal risk factors associated with low birth weight in Karachi: a case-control
      study.
AB  - To evaluate maternal risk factors associated with low birth weight (LBW) among
      women aged 15-35 years, we carried out a hospital-based, case-control study on
      262 cases (mothers of neonates weighing < or = 2.5 kg) and 262 controls (mothers
      of neonates weighing > 2.5 kg). Odds of delivering a low-birth-weight baby
      decreased with increase in maternal haemoglobin [odds ratio (OR): 0.701; 95%
      confidence interval (CI): 0.62-0.79]. Odds were greater among mothers not using
      iron supplements during pregnancy (OR: 2.88; 95% CI: 1.83-4.54). Mothers of LBW
      babies had lower haemoglobin levels before delivery.

PMID- 18341185
TI  - Maternal characteristics in relation to income in a semi-rural community in
      Pakistan.
AB  - Women's health and socioeconomic status is fundamental to development. The aim of
      this study was to evaluate the relationship of monthly household income with
      demographic, nutritional and social characteristics in women living in a semi
      rural location near Karachi. Thus 1111 mothers with at least 1 child under 5
      years of age were interviewed. Self-reported monthly income was positively
      associated with gravidity, mid upper-arm circumference, cooking frequency per day
      and self and spousal literacy; it was negatively associated with number of
      occupants per room, wood used as cooking fuel, and spouse in a skilled
      occupation. Income is dependent on non-income factors such as literacy, and the
      nutritional and reproductive health status of women.

PMID- 18341186
TI  - Fertility and its relationship with sociocultural factors in Kuwaiti society.
AB  - The aim of this study was to examine the effect of some sociocultural variables
      on the fertility of Kuwaiti women. A questionnaire was administered to a sample
      of 7749 married women (aged 15-78 years) selected randomly from 10 primary health
      care clinics in Kuwait. The fertility rate was 3.58 live births per woman.
      Fertility was higher among Sunni Muslim women, those of Bedouin ethnicity, and
      those in a consanguineous marriage (P < 0.001). There was a significant negative
      relationship between fertility and respondents' educational level, occupation,
      age at marriage, socioeconomic status and type of marriage (consanguineous or
      not). There was a positive relationship between fertility and the respondents'
      age and the family income.

PMID- 18341187
TI  - Utilization of family planning services by married Sudanese women of reproductive
      age.
AB  - To explore differences in utilization of family planning services and
      predisposing factors, we surveyed 601 women from urban and rural areas of
      Khartoum state. About half were using modern family planning techniques; there
      were no significant differences in utilization rates between urban and rural
      settings. Contraceptive pills were the most frequently used modern method (47.7%)
      followed by intrauterine devices (10.2%) and injections (7.5%). Breastfeeding was
      used by around 33% of both groups. The rhythm method and withdrawal were more
      often used by urban women (22.2% and 8.6% respectively) than rural women (16.1%
      and 3.6% respectively). Use of male methods (condom; sterilization) was extremely
      low. Socioeconomic status, knowledge and education level were the most important
      determinants of using modern methods.

PMID- 18341188
TI  - Family planning and unmet need among Iraqi Kurds.
AB  - This study in Dohuk district of Kurdistan region, northern Iraq, in 2003
      estimated the prevalence of contraceptive use and unmet need, and investigated
      associated knowledge, attitudes and practices. With multi-stage sampling, 800
      married women aged 15-49 years were interviewed. Current prevalence of
      contraceptive use (any method) among 668 non-pregnant women was 60.6%: use of
      modern methods was 26.5% and traditional methods was 34.1%. Among all
      respondents, current unmet need for any contraception was 29.3% (most commonly
      among women of low socioeconomic status) and that for modern (effective)
      contraception was 28.5% (most commonly among women of high socioeconomic status).
      A comprehensive and decentralized family planning programme needs to be
      implemented in the region.

PMID- 18341189
TI  - Unintended pregnancy in Egypt: evidence from the national study on women giving
      birth in 1999.
AB  - The current study aimed to estimate the prevalence and correlates of unintended
      pregnancy among ever-married women. The study sample was 2349 ever-married women
      aged 15-49 years who gave birth in 1999. Unintended pregnancy was defined as
      unwanted and mistimed pregnancies. Of these, 431 (18.5%) women reported
      unintended pregnancy: 137 were mistimed (5.9%) and 294 were unwanted (12.6%).
      Women of older age, living in frontier governorates, with poor knowledge of the
      ovulatory cycle, having a more than ideal family size, using contraceptive
      methods and having 4 or more children were at increased odds of reporting
      unintended pregnancies. Fewer antenatal care visits and low child weight at birth
      were significantly associated with unintended pregnancy.

PMID- 18341190
TI  - Condom use among males (15-49 years) in Lower Egypt: knowledge, attitudes and
      patterns of use.
AB  - We conducted a cross-sectional study on a randomly selected sample of 2304 males
      aged 15-49 years from 4 governorates in Lower Egypt to assess their condom use
      and knowledge and attitudes towards condom use. Condoms were considered an
      effective method of contraception and prevention of transmission of sexually
      transmitted infections (STIs) by 60.5% and 60.0% respectively. Only 23.9% had
      ever used condoms, mainly for contraception, but 26.8% would consider using them
      in the future. A quarter reported knowing how to use condoms properly. Obstacles
      to condom use included perceived lack of need (75.7%), rejection by partner
      (57.6%) and hazards of condoms (31.9%). The majority knew about HIV/AIDS (90.8%)
      but a few felt at risk of STIs (11.2%) or HIV infection (10.3%).

PMID- 18341191
TI  - Prevalence of and reasons for domestic violence among women from low
      socioeconomic communities of Karachi.
AB  - We conducted a cross-sectional study to estimate the prevalence of domestic
      violence and identify the reasons for it among 400 married women aged 15-45 years
      in low socioeconomic areas in urban Karachi. Data were collected with a pretested
      questionnaire. The prevalence of verbal abuse was 97.5% by the husband and 97.0%
      by the in-laws; the prevalence of physical abuse was 80.0% and 57.5% by the
      husband and in-laws respectively. Financial issues were the commonest reason for
      domestic violence followed by infertility and not having a son. The prevalence of
      domestic violence in our sample of women is high. There is a need to address this
      problem with efforts from health workers, policy-makers, nongovernmental
      organizations and others.

PMID- 18341192
TI  - Assessment of the pharmaceutical quality of omeprazole capsule brands marketed in
      Egypt.
AB  - The pharmaceutical quality of 7 local omeprazole capsule brands in Egypt was
      assessed relative to the proprietary product (Losec). Drug content, content
      uniformity, drug release (using USP test for enteric coated articles and a
      modified release test) were determined. Products were subjected to a 3-month
      stability study. Of the 7 brands, 6 had satisfactory drug content and content
      uniformity. All brands passed the USP drug release test. The modified release
      test proved to be more discriminative. After 3 months storage, drug content of 3
      brands remained > 90% and 2 of these brands maintained drug release above 75%.
      Changes in pellet appearance during storage were indicative of omeprazole
      chemical degradation.

PMID- 18341193
TI  - Environmental behavioural modification programme for street children in
      Alexandria, Egypt.
AB  - An environmental behavioural modification programme was implemented in Alexandria
      city, Egypt, in order to help street children to change their behaviour, discover
      their abilities and develop and acquire new skills and knowledge. The programme
      included camping and field trips, recreational activities and games, role play
      and theatre, story-telling, life-skill activities, and gardening and animal care.
      Data were collected from observational sheets of adaptive behaviour and
      conversation sessions before and after the intervention on a sample of 35 street
      children aged between 7 and 15 years. The mean scores for each behavioural item
      and all items together before and after the intervention were significantly
      improved in a number of areas, except for speech disorders and substance use.

PMID- 18341194
TI  - Characteristics and risk factors of tobacco consumption among University of
      Sharjah students, 2005.
AB  - This study aimed to estimate the prevalence, patterns and risk factors of tobacco
      consumption among a stratified random sample of students at University of
      Sharjah, United Arab Emirates (UAE), during 2005. The overall reported smoking
      prevalence among 1057 sampled students was 15.1%; cigarette smokers were 9.4% and
      waterpipe smokers 5.6%. While women comprised only 8.9% of cigarette smokers,
      they were 26.2% of waterpipe smokers. Multiple linear regression analysis showed
      that the most important predictors for smoking among the students were: male sex,
      having a smoking friend, having a smoking family member (father/mother/both), non
      UAE nationality and older age. There is a need to intensify efforts to prevent
      young people from starting smoking and to help young smokers to stop.

PMID- 18341195
TI  - Women's empowerment and health: the role of institutions of power in Pakistan.
AB  - Women's right to health has been reiterated many times. However, there are social
      and cultural barriers in developing countries that hinder their empowerment.
      Women's low status, deprivation of education and lack of control over their own
      lives and bodies have a negative impact on their health status and that of their
      families. This paper discusses women's empowerment and health within the
      framework of the 4 institutions of power in a society-family, community, health
      care systems and the state--with special reference to the situation in Pakistan.
      It concludes that to improve women's health status, concerted efforts are needed
      by all these institutions of power to work towards gender equality and the
      greater empowerment of women.

PMID- 18341196
TI  - Impact of rural health development programme in the Islamic Republic of Iran on
      rural-urban disparities in health indicators.
AB  - By 1979 50 years of uneven development and modernization by governments prior to
      the Islamic Revolution had left rural parts of the Islamic Republic of Iran with
      extremely low economic and health status. This paper reports on the impact of the
      rural health development programme implemented as an effective and inexpensive
      way to improve the heath of the rural population, especially mothers and
      children. It describes the system of rural health centres, health houses and
      community health workers (behvarz) and demonstrates the effectiveness of the
      programme through declining measures of rural-urban disparities in health
      indicators. The implications of inexpensive rural health policies for other
      countries in the region such as Afghanistan and Central Asian countries with a
      similar sociocultural structure are discussed.

PMID- 18341197
TI  - Achieving sustainability, quality and access: lessons from the world's largest
      revolving drug fund in Khartoum.
AB  - Ensuring a reliable and affordable supply of essential drugs to health facilities
      is one of the main challenges facing developing countries. This paper describes
      the revolving drug fund in Khartoum, which was set up in 1989 to improve access
      to high quality drugs across the State. An evaluation in 2004 showed that the
      fund has successfully managed a number of threats to its financial sustainability
      and has expanded its network of facilities, its range of products and its
      financial assets. It now supplies essential drugs to 3 million out of the 5
      million population of Khartoum each year, at prices between 40% and 100% less
      than alternative sources. However, results illustrated the tension between
      achieving an efficient cost-recovery system and access for the poorest.

PMID- 18341198
TI  - Cancer magnitude, challenges and control in the Eastern Mediterranean region.
AB  - Cancer is increasingly recognized as a major and growing health concern in the
      Eastern Mediterranean Region (EMR). This report outlines the current burden of
      cancer in the Region and the challenges faced by the countries; these are mainly
      lack of national cancer surveillance, lack of a model of integrated care for
      noncommunicable disease prevention in general and cancer in particular,
      inadequate national capacity-building and lack of programme sustainability.
      Strategies for cancer prevention, control and care in the Region are discussed,
      such as: the formulation of evidence-based policies, mobilization and appropriate
      allocation of resources, active participation of all stakeholders, government
      commitment to legislation, education and international collaboration.

PMID- 18341199
TI  - Study on child labour in automobile workshops of Peshawar, Pakistan.
AB  - To determine the characteristics of children working in car workshops in
      Peshawar, a descriptive survey was conducted from June to November 2005 of 200
      boys (6-15 years) randomly selected from 32 workshops. A questionnaire was used
      to collect socioeconomic and work-related data. The majority of the boys had no
      or little education, had started work before the age of 10 years and earned <700
      rupees/month. Most of their fathers had little education and were in poorly paid
      jobs, unemployed or deceased. About 40% of the boys were engaged in mechanical
      work. Watery eyes (31%), chronic cough (29%) and diarrhoea (22%) were the
      commonest symptoms reported by the boys and 38% had had a major injury.

PMID- 18341200
TI  - Human immunodeficiency virus-1 Tat protein: immunological facets of a
      transcriptional activator.
AB  - Human immunodeficiency virus-1 (HIV-1) infection is characterized by chronic
      immune activation and progressive loss of CD4+ T cells, leading to a wide array
      of immune dysfunction, particularly involving immune response directed against
      viral antigens. HIV-1 encodes for fifteen proteins, which might serve as a target
      for immune recognition. Immune response to the envelope proteins have been
      studied more due to their presence on the surface of the virus. Recent studies on
      HIV vaccine development have focused on the Gag and Pol proteins. The
      transactivator Tat and Rev proteins have also been the focus of immunization
      studies due to their potent regulatory activity. The Tat (transactivator of
      transcription) protein although being nuclear in localization is also released
      from infected cells and acts on uninfected cells. Extracellular Tat seems to play
      an important role in AIDS pathogenesis. Furthermore, a correlation has been found
      between anti-Tat immune response and slow progression of the disease. Although
      several studies have shown Tat as a potential vaccine candidate with encouraging
      results, there are also reports raising doubt about its efficacy in multi
      component HIV vaccine strategy. Here, we have addressed the issue of immune
      response to the most indispensable HIV-1 regulatory protein Tat.

PMID- 18341201
TI  - Cellular AATF gene: armour against HIV-1.
AB  - Outcome of HIV-1 infection at the cellular level is decided by the orchestrated
      balance that exists between cellular nucleic acid-based adaptive immune mechanism
      involving non-coding micro RNAs (miRNAs) and offensive tactics of HIV-1 to
      suppress this host cellular immunity. In this context, the review explains the
      importance of a novel miRNA encoded exclusively and conspicuously by HIV-1 genome
      that has the ability to specifically target cellular AATF gene recognized to play
      a crucial role in the maintenance of adaptive immunity at nucleic acid level
      against HIV-1 invasion.

PMID- 18341202
TI  - Mycobacterium tuberculosis and dendritic cells: recognition, activation and
      functional implications.
AB  - The highly complex nature of interactions of Mycobacterium tuberculosis with
      cells of the immune system has puzzled researchers the world-over in
      understanding the pathogenesis and immunology associated with tuberculosis (TB).
      This has contributed to the delay in development of effective vaccine(s) for TB.
      Several excellent studies have provided only a glimpse of the kind and degree of
      immune responses elicited following infection by mycobacteria. Preferred entry
      via respiratory route results in the capture of mycobacteria by alveolar
      macrophages that eventually become their long-term hosts. Since the pathogen is
      rarely cleared this has resulted in the human population serving as a large
      reservoir for mycobacteria. Owing to their unique ability to prime naive and
      memory T cells, dendritic cells (DCs) play important and indispensable roles in
      the initiation and maintenance of protective immune responses following
      infection. The kind of immune response initiated by DCs with respect to
      mycobacteria determines the character of immune responses mounted by the host
      against the pathogen. The profile of cytokines and chemokines secreted as a
      result of infection of DCs by mycobacteria further plays an important role in
      defining the course of infection. This minireview attempts to highlight key
      interactions of mycobacteria with dendritic cells. We discus the uptake of
      mycobacteria by DCs followed by DC activation and the spectrum of immune
      responses initiated by infected/activated DCs, followed by numerous ways the
      pathogen has devised to subvert protective responses.

PMID- 18341203
TI  - Type II phosphatidylinositol 4-kinase(s) in cell signaling cascades.
AB  - Phosphorylated derivatives of phosphatidylinositol (PtdIns) are key components of
      many signaling cascades. Many isoforms of PtdIns kinases, PtdIns phosphate
      kinases and phosphatases use these lipids in amazing networks of signaling
      cascades that are yet to be understood fully. PtdIns 4-kinase(s) phosphorylates
      PtdIns at the 4th -OH position of inositol head group and are classified in to
      type II and III PtdIns 4-kinases. While type III PtdIns 4-kinases are implicated
      in vesicular trafficking, type II PtdIns 4-kinases are suggested to play a role
      in cell signaling, cytoskeletal rearrangements, cell motility and in microbial
      pathogenicity. This paper reviews the role of type II PtdIns 4-kinases in cell
      signaling cascades in health and disease.

PMID- 18341204
TI  - Prodigiosins: a novel family of immunosuppressants with anti-cancer activity.
AB  - Prodigiosins (PrGs) are a family of promising therapeutic molecules, isolated
      mostly from Gram-negative bacteria and characterized by a common
      pyrryldipyrrylmethene structure with varying side chains. They show a broad
      spectrum of activities such as anti-microbial, anti-malarial, anti-cancer and
      immunosuppressive. PrGs are attracting increasing attention due to the ongoing
      research for less toxic, but effective agents for cancer chemotherapy and
      immunosuppression for preventing allograft rejection and autoimmunity. Different
      analogues have been synthesized and evaluated. This review discusses the
      immunosuppressive and anti-cancer activities of this class of compounds, as both
      involve inhibition of cell proliferation. The main focus is on the in vitro and
      in vivo immunosuppressive activity of the different PrGs and the mechanisms
      involved. PrGs primarily target the T cells, though some effects are observed on
      other cell types also. Unlike the well-known immunosuppressant cyclosporin A,
      PrGs do not inhibit the secretion of IL-2 but inhibit the mitogenic signaling
      from IL-2, suggesting a different mechanism of action. Janus tyrosine kinase 3
      (Jak3) that associates with IL-2R upon activation is considered as the molecular
      target for PrGs. Its restricted expression makes Jak3 as an attractive target for
      immunosuppressive therapy. However, the available literature suggests that some
      other pathways are also influenced by the PrGs. These may be important for the
      anti-cancer activity, as well as immunosuppressive action. Therefore, PrGs appear
      to be potential candidates for pharmaceutical development as immunosuppressants
      and also as anti-cancer agents.

PMID- 18341205
TI  - Inducible nitric oxide synthase (iNOS): role in asthma pathogenesis.
AB  - Asthma is one of the most common chronic inflammatory disorder of the airways of
      the lungs, affecting more than 300 million people all over the world. Nitric
      oxide (NO) is endogenously produced in mammalian airways by nitric oxide synthase
      (NOS) and is known to regulate many aspects of human asthma, including the
      modulation of airway and vascular smooth muscle tone and the inflammation.
      Asthmatic patients show an increased expression of inducible nitric oxide
      synthase (iNOS) in airway epithelial cells and an increased level of NO in
      exhaled air. Using various NO inhibitors (non-specific or iNOS-specific) and gene
      knock-out experiments, controversial results have been obtained regarding iNOS's
      beneficial and deleterious effects in the disease. In the present review, we have
      attempted to summarize the results of these experiments and also the genetic
      studies being undertaken to understand the role of iNOS in asthma. It is argued
      that extensive biochemical, clinical and genetic studies will be required to
      assess the precise role of NO in the asthma. This may help in designing selective
      and more potent iNOS inhibitors and NO donors for developing novel therapeutics
      for the asthma patients.

PMID- 18341206
TI  - Nitric oxide and immune response.
AB  - Nitric oxide (NO), initially described as a physiological mediator of endothelial
      cell relaxation plays an important role in hypotension. It is an intercellular
      messenger and has been recognized as one of the most versatile players in the
      immune system. Cells of the innate immune system--macrophages, neutrophils and
      natural killer (NK) cells use pattern recognition receptors to recognize
      molecular patterns associated with pathogens. Activated macrophages then inhibit
      pathogen replication by releasing a variety of effector molecules, including NO.
      In addition to macrophages, a large number of other immune system cells produce
      and respond to NO. Thus, NO is important as a toxic defense molecule against
      infectious organisms. It also regulates the functional activity, growth and death
      of many immune and inflammatory cell types including macrophages, T lymphocytes,
      antigen-presenting cells, mast cells, neutrophils and NK cells. However, the role
      of NO in non-specific and specific immunity in vivo and in immunologically
      mediated diseases and inflammation is poorly understood. This review discusses
      the role of NO in immune response and inflammation and its mechanisms of action
      in these processes.

PMID- 18341207
TI  - Immunological, cellular and molecular events in typhoid fever.
AB  - Salmonella, a facultative intracellular Gram-negative bacterium infects a wide
      range of hosts causing several gastrointestinal diseases and enteric fever in
      humans and certain animal species. Typhoid caused by Salmonella typhi remains a
      major health concern in India and worldwide. Also, with emergence of multidrug
      resistant strains, Salmonella has acquired increased virulence, communicability
      and survivability, resulting in increased morbidity and mortality. Though a
      number of vaccines for typhoid are available against S. typhi (or also against S.
      typhimurium), these have certain undesirable side effects and the search for new
      immunogens suitable for vaccine formulation is still continuing. The immune
      response to primary Salmonella infection involves both humoral and cell-mediated
      responses. The protective immunity against Salmonella depends on host- parasite
      interaction, however; the detailed mechanism of virulence, innate resistance and
      susceptibility of host remains unclear. This review focuses on the molecular,
      immunological and cellular mechanisms of pathogenesis of Salmonella infection to
      provide an insight to counteract bacterial infections and allow a better
      understanding of its clinical manifestations. It also reviews better
      technological possibilities combined with increased knowledge in related fields
      such as immunology and molecular biology and allow for new vaccination
      strategies. Some new approaches such as subunit and nucleic acid vaccines and
      recombinant antigen which are becoming increasingly important for the development
      of potential vaccines have also been discussed. A significant progress has been
      made in our understanding of Salmonella pathogenesis. Despite these efforts,
      however, many challenges exist, especially for investigators who aim to
      understand how the pathogenic mechanisms operating in vitro apply to in vivo
      model systems. However, unyielding work and collaborations between Salmonella
      researchers and clinicians worldwide have made significant contributions to
      understanding the interaction between virulence determinants and immunity
      required to stop the spread of this pathogen.

PMID- 18341208
TI  - Viral complement regulators: the expert mimicking swindlers.
AB  - The complement system is a principal bastion of innate immunity designed to
      combat a myriad of existing as well as newly emerging pathogens. Since viruses
      are obligatory intracellular parasites, they are continuously exposed to host
      complement assault and, therefore, have imbibed various strategies to subvert it.
      One of them is molecular mimicry of the host complement regulators. Large DNA
      viruses such as pox and herpesviruses encode proteins that are structurally and
      functionally similar to human regulators of complement activation (RCA), a family
      of proteins that regulate complement. In this review, we have presented the
      structural and functional aspects of virally encoded RCA homologs (vRCA), in
      particular two highly studied vRCAs, vaccinia virus complement control protein
      (VCP) and Kaposi's sarcoma-associated herpesvirus complement regulator
      (kaposica). Importance of these evasion molecules in viral pathogenesis and their
      role beyond complement regulation are also discussed.

PMID- 18341209
TI  - Role of T-cells in diabetic pregnancy and macrosomia.
AB  - A number of studies have recently addressed the correlationship between diabetic
      pregnancy/macrosomia and differentiation of T-cells into Th1 and Th2 subsets.
      Diabetic pregnancy has been found to be associated with a decreased Th1 phenotype
      and IL-4 mRNA expression. In macrosomic offspring, high expression of IL-2 and
      IFN-gamma mRNA, but not of Th2 cytokines is observed, indicating that the Th1
      phenotype is upregulated during macrosomia. T-cells of gestational diabetic rats
      and their macrosomic offspring seem to present a defect in signal transduction.
      Indeed, the recruitment of free intracellular calcium concentrations from
      intracellular pool in T-cells of these animals is altered. The phenotype of
      regulatory T-cells (T-Reg) is upregulated in diabetic pregnancy and their
      infants. T-cells in diabetic pregnancy and macrosomic obese offspring are in vivo
      activated. Adipokines and peroxisome proliferator-activated receptor-alpha
      (PPARalpha) also seem to modulate the pro-inflammatory cytokines in these
      pathologies. Hence, activation of the immune system might be considered as one of
      the regulatory pathways including metabolic abnormalities in these two
      pathologies.

PMID- 18341210
TI  - Role of IL-10 in immune suppression in cervical cancer.
AB  - Cervical cancer is the second most common cancer in the women worldwide and the
      most frequent in developing countries, including India. Human papilloma virus
      (HPV) is the major etiological factor in cervical cancer patients. Host factors
      are also critical in regulating tumor growth and cytokines that modulate
      immunologic control may be of particular importance. In the present study, we
      investigated the correlation between the presence of HPV and type of cytokines
      expressed in cervical carcinomas and attempted to elucidate the possible reasons
      for the immune suppression. Cytokines investigated were type-1 cytokine IFN-gamma
      (shows immunostimulatory function and capable of limiting tumor growth) and type
      2 cytokines IL-4, IL-10 and IL-6 (show immunosuppressive function and capable of
      stimulating tumor growth). Our data demonstrated the presence of HPV sub-types 16
      and 18 in 86% and 13.8% of cervical tumor biopsies, respectively. The cervical
      tumor biopsies showed increased presence for mRNA for IL-10 and IL-1alpha, while
      none of the biopsies showed expression for IFN-gamma. A correlation was observed
      between the presence of HPV in cervical tumor biopsies and mRNA for IL-10.
      Increased percentages of CD4+CD25+ regulatory T cells (Tregs) were observed in
      circulation in cervical cancer patients, providing evidence for increased immune
      suppression. IL-10 may play a key role in maintenance of Tregs and explains the
      immunosuppressive state of cervical cancer patients.

PMID- 18341211
TI  - Comparative analysis of differential expression of sialic acids and adhesion
      molecules on mononuclear cells of bone marrow and peripheral blood in childhood
      acute lymphoblastic leukaemia at diagnosis and clinical remission.
AB  - Childhood acute lymphoblastic leukaemia (ALL) is characterized by the neoplasm of
      immature haematopoietic precursor cells (HPCs). We report significant differences
      between the expression of sialoglycoproteins and adhesion molecules on
      mononuclear cells (MNCs) of bone marrow (BM) and peripheral blood (PB) from
      individual children at diagnosis of the disease. Lymphoblasts in PB predominantly
      expressed 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs), sialic acid, alpha2
      3 linked sialic acid, L- and P-selectins and vascular cell adhesion molecule -1
      (VCAM-1) on their surface compared to BM, as determined with selective lectins
      and monoclonal antibodies (mAbs) by flow cytometric analysis. CD34+CD38+ cells
      present either in diagnostic PB or BM always showed enhanced expression of both
      alpha2-3 and alpha2-6 linked sialic acids, Neu5,9Ac2-GPs, L- and P-selectins and
      VCAM-1, compared to CD34+CD38- population, as confirmed by higher mean
      fluorescence intensity (MFI). Expression of ICAM-1 was reverse. However, MFI of
      Neu5,9Ac2-GPs was always higher both in CD34+CD38+ and CD34+CD38- population in
      PB compared to BM. Diverse trend of these cell surface macromolecules was
      observed during clinical remission. This is the first comparative study between
      PB and BM, where significant differential distribution of sialylated
      macromolecules and adhesion molecules was observed. Hence, supervising these cell
      surface macromolecules at various stages of treatment might help in minimal
      residual disease detection, identifying mobilization factor(s) and in isolation
      of normal HPCs for autologous BM transplantation.

PMID- 18341212
TI  - Immunomodulatory role of arabinosylated lipoarabinomannan on Leishmania donovani
      infected murine macrophages.
AB  - Arabinosylated lipoarabinomannan (Ara-LAM), a surface glycolipid antigen isolated
      from avirulent Mycobacterium smegmatis is involved in modulation of host cell
      signaling. In this study, we investigated Ara-LAM-mediated modulation of impaired
      immune responses during visceral leishmaniasis caused by protozoan parasite
      Leishmania donovani. Ara-LAM treatment at dose of 3 microg/ml in L. donovani
      infected murine peritoneal macrophages as well as J774A.1 macrophage cell line
      exhibited a distinct up-regulation of pro-inflammatory cytokines like TNF-alpha
      and IL-12 both at the protein and transcriptional level. In addition, generation
      of nitric oxide and iNOS expression were also observed. The present study showed
      that Ara-LAM was significantly effective in elimination of L. donovani parasites
      from both peritoneal as well as J774A.1 macrophages. Thus, it could be utilized
      as an immunomodulatory agent in prevention of leishmanial pathogenesis.

PMID- 18341213
TI  - Advanced glycosylated end products-mediated activation of polymorphonuclear
      neutrophils in diabetes mellitus and associated oxidative stress.
AB  - Two important consequences of hyperglycemia in diabetes are development of
      oxidative stress and formation of advanced glycation end products (AGE) which are
      known to be associated with diabetic complications. Relationship between AGE
      formation and development of oxidative stress (OS) is yet to be established. In
      the present study, the involvement of AGE in PMN-mediated ROS generation and the
      associated OS were investigated in type 2 diabetic mellitus (DM) patients. We
      assessed OS parameters (serum MDA, FRAP and GSH), PMN oxidative functions
      (respiratory burst and superoxide production) and total serum AGE in 90 subjects
      divided equally in three groups--control group, Group I consisting of type 2
      diabetic patients without microvascular complications and Group II consisting of
      type 2 diabetic patients with microvascular complications. PMNs isolated from
      both groups (I and II) exhibited higher level of respiratory burst (RB) and
      produced increased amount of superoxide anion as compared to the controls. The
      increase was more pronounced in diabetes with complications, as compared to those
      without. Serum malondialdehyde (MDA) level was elevated, whereas glutathione
      (GSH) and ferric reducing ability of plasma (FRAP) levels were significantly
      reduced in diabetes as compared to the controls, suggesting the presence of
      oxidative stress in DM. A positive correlation between PMN oxidative function and
      OS parameters suggested the involvement of PMN in the development of OS in DM.
      Serum AGE level was also elevated in diabetic groups as compared to the controls.
      Further, the positive correlation between serum AGE level and PMN oxidative
      function suggested the involvement of AGE in increased RB and generation of
      reactive oxygen species (ROS) by resting diabetic PMN. The results of the study
      indicate that AGE-PMN interaction possibly upregulates NADPH oxidase, leading to
      enhanced ROS generation and thus contributes to the pathogenesis in diabetes.

PMID- 18341214
TI  - Partial purification and characterization of acetylcholinesterase isozymes from
      adult bovine filarial parasite Setaria cervi.
AB  - Filariasis is a major health problem, affecting millions of people in tropical
      and sub-tropical regions of the world. The isolation and characterization of
      parasite-specific enzyme targets is essential for developing effective control
      measures against filariasis. Acetylcholinesterase (AchE, E.C. 3.1.1.7), an
      important enzyme of neuromuscular transmission is found in a number of helminths
      including filarial parasites and may be playing a role in host-parasite
      interactions. Earlier, we demonstrated the presence of two isozymes of AchE,
      different from the host enzyme in the human (Brugia malayi) and bovine (Setaria
      cervi) filarial parasites. In the present study, two isozymes of AchE (pAchE1 and
      pAchE2) were isolated from S. cervi adults and characterized biochemically and
      immunochemically. The AchE was partially purified on Con-A Sepharose column and
      then subjected to preparative polyacrylamide gel electrophoresis (PAGE) for
      separation of the isozymes. The AchE activity was localized by the staining of
      gel and the isozymes were isolated from the PAGE strips by electroelution. Both
      isozymes preferentially utilized acetylcholine iodide as substrate and were
      strongly inhibited by the true AchE inhibitor (BW284c51), suggesting that they
      were true AchE. The polyclonal antibodies produced against the isozymes showed
      significant cross-reactivity with B. malayi AchE, but not against the host
      enzyme. These findings suggested that both the isozymes were biochemically (in
      terms of their substrate specificity and inhibitor sensitivity) and
      immunochemically similar, but different from the host enzyme.

PMID- 18341215
TI  - Liposomal delivery of Mycobacterium leprae antigen(s) with murabutide and Trat
      peptide inhibits Fas-mediated apoptosis of peripheral blood mononuclear cells
      derived from leprosy patients.
AB  - Protective immunity against intracellular pathogen Mycobacterium leprae is
      dependent on the activation of T cells. Repeated stimulation of T cells by M.
      leprae antigens MLCwA (M. leprae total cell wall antigen) and ManLAM (mannose
      capped lipoarabinomannan) may lead to apoptosis in leprosy patients. In the
      present study, inhibition of the Fas-induced apoptosis of peripheral blood
      mononuclear cells of leprosy patients was investigated using above M. leprae
      antigen(s), in combination with immunomodulators murabutide (MB) and a Trat
      peptide in particulate form (liposome). Incubation of the cells with particulate
      mode of antigen presentation led to both decreased percentage of propidium iodide
      (PI) positive cells and T cells expressing Fas-FasL, as well as decreased caspase
      8/-3 activities in the lepromatous patients, thereby inhibiting apoptosis, while
      converse was true with stimulation with soluble antigen. Concurrently, there was
      an upregulation of antiapoptotic protein Bcl-X(L) in the lepromatous patients,
      thereby inhibiting apoptosis. Thus, the liposomal formulation of antigen promoted
      proliferation of anergized T cell by inhibiting apoptosis through decreased
      expression of death receptors and caspase activities and increased expression of
      anti-apoptotic protein Bcl-X(L) in these patients.

PMID- 18341216
TI  - Correlation of circulatory immunoglobulin levels with Mu opiate receptor allele.
AB  - Opiates are known to induce immunosuppression in their users (addicts). Evidences
      supporting their role in suppressing a variety of immunological end points in
      addicts have been reported by several investigators. In the present study, we
      investigated the changes in serum immunoglobulin (Ig) levels and their
      correlation with Mu opiate receptor (MOR) genotypes. Eighty-seven users and forty
      five non-users were recruited for the study. Genomic DNA, isolated from the
      peripheral blood, was used for genotyping for C17T and A118G polymorphism using
      PCR-RFLP method. The frequency of A and G alleles in non-users was 89% and 11%
      respectively, whereas in addicts, it was 67% and 33% respectively. Case control
      analysis between groups revealed that 118G allele was associated with opioid
      dependence [Chi square (chi2) = 13.56, odds ratio (OR) = 3.90, confidence
      interval 95% (CI 95%) = 1.80-8.67, p = 0.000231]. C17T polymorphism showed no
      association with opioid dependence [(chi2) = 0.9, OR = 2.49, CI 95% = 0.528
      16.12, p = 0.343]. Mean Ig levels, both IgG (student's t-test = 2.2738, p =
      0.007) and IgA (student's t-test = 2.848, p = 0.0051) differed between opiate
      users and nonusers. IgG and IgA levels were also significantly different in
      individuals with different MOR genotypes. Immunosuppression was observed in AA
      genotype-bearing individuals, while no suppression was seen in AG and GG
      genotypes bearing individuals. In case of C17T polymorphism, both CC and CT
      genotypes bearing individuals showed immunosuppression, as judged by circulating
      Ig levels.

PMID- 18341217
TI  - Role of virulence plasmid of Aeromonas hydrophila in the pathogenesis of
      ulcerative disease syndrome in Clarias batrachus.
AB  - Pathogenic Aeromonas hydrophila (strain VB21), a multiple-drug resistance strain
      contains a plasmid of about 21 kb. After curing of plasmid, the isolates became
      sensitive to antimicrobials, to which they were earlier resistant. The cured
      bacteria exhibited significant alterations in their surface structure, growth
      profile and virulence properties, and failed to cause ulcerative disease syndrome
      (UDS) when injected into the Indian catfish Clarias batrachus. Routine
      biochemical studies revealed that the plasmid curing did not alter the
      biochemical properties of the bacteria. After transformation of the plasmid into
      cured A. hydrophila the bacterium regained its virulence properties and induced
      all the characteristic symptoms of UDS when injected into fish. Thus, the plasmid
      plays a pivotal role in the phenotype, growth and virulence of A. hydrophila and
      pathogenesis of aeromonad UDS.

PMID- 18341218
TI  - Understanding safety of glutamate in food and brain.
AB  - Glutamate is ubiquitous in nature and is present in all living organisms. It is
      the principal excitatory neurotransmitter in central nervous system. Glutamate is
      being used as food additive for enhancing flavour for over last 1200 years
      imparting a unique taste known as "umami" in Japanese. It is being marketed for
      about last 100 years. The taste of umami is now recognized as the fifth basic
      taste. Many of the foods used in cooking for enhancing flavour contain high
      amount of glutamate. Breast milk has the highest concentration of glutamate
      amongst all amino acids. Glutamate in high doses as gavage or parenteral
      injection have been reported to produce neurodegeneration in infant rodents. The
      neurodegeneration was not produced when gluamate was given with food. The Joint
      FAO/WHO Expert Committee on Food Additives, based on enumerable scientific
      evidence, has declared that, "glutamate as an additive in food" is not an health
      hazard to human being. Glutamate is used as signaling molecule not only in
      neuronal but also in non-neuronal tissues. Excessive accumulation of glutamate in
      the synaptic cleft has been associated with excitotoxicty and glutamate is
      implicated in number of neurological disorders. Excessive accumulation could be
      attributed to increase release, failure of transport system for uptake mechanism,
      neuronal injury due to hypoxia-ischemia, trauma and associated metabolic
      failures. The role blood brain barrier, vesicular glutamate and sodium dependent
      excitatory amino acid transporters in glutamate homeostasis are emphasized in the
      review.

PMID- 18341219
TI  - Assessment of respiratory and sympathetic cardiovascular parameters in obese
      school children.
AB  - The study was undertaken to assess the respiratory and sympathetic cardiovascular
      functions in obese and non obese school children of 12-16 years age group,
      randomly selected from two schools of Rajpura (Punjab), representing mixed
      socioeconomic group of Punjabi ethnicity and categorized as obese or controls as
      per standard criteria for Body Mass Index (BMI). Dynamic lung function tests and
      pressor response to cold (Cold pressor test) and isometric exercise (Handgrip
      dynamometer test) were carried out. Statistical analysis comprised students' t
      test, at 95% confidence level and simple linear regression analysis. The results
      indicated significantly higher baseline diastolic blood pressure (DBP) (P <
      0.004) in obese children correlating positively with BMI (r = 0.57).
      Significantly increased DBP response to applied cold stimulus (response/range, P
      < 0.02 and maximal value, P < 0.001) and borderline response to isometric
      exercise (P < 0.002) in obese children indicated autonomic instability. The
      dynamic lung functions were significantly decreased (P < 0.04) in obese subjects
      and correlated negatively with BMI. Personal data forms of obese children
      revealed less physical activity and excessive intake of junk foods. Thus it is
      concluded that obese children have derangement of sympathetic cardiovascular
      functions and reduced pulmonary functions.

PMID- 18341220
TI  - Pulmonary functions in petrol pump workers: a preliminary study.
AB  - Occupational exposures to petrol/diesel vapors have been shown to affect
      functioning of different systems of the body. The present study was planned to
      assess the pulmonary functions in petrol pump workers (filling attendants) who
      are continuously exposed to petrol/diesel vapors during duty hours. Thirty
      healthy non-smoker males working in petrol pump for more than one year formed the
      study group, while thirty healthy non-smoker males from hospital staff served as
      control group. The pulmonary functions were assessed using computerized
      spirometer. The FVC and FEV1 were decreased in the study group while their ratio
      did not differ much. Both the inspiratory and expiratory flow rates were also
      decreased in the study group. These findings point towards adverse effects of
      petrol/diesel fumes mainly on lower airways with restrictive pattern of disease.

PMID- 18341221
TI  - Decline in respiratory performance of Varanasi population in 22 years: a cross
      sectional study.
AB  - Lung function tests were performed on apparently healthy, non-smoking male
      volunteers aged 16-50 years normally staying in Varanasi city area. The
      volunteers were divided into five groups according to their age (16-19 yr, 20-25
      yr, 26-30 yr, 31-35 yr, 40-50 yr). Anthropometric determinants (height and
      weight) and respiratory performance (vital capacity and peak expiratory flow
      rate) were recorded in the year 1982 and 2004. No significant (P>0.05) difference
      in height, weight and body mass index was detected between the age matched groups
      in the year 1982 and 2004. The Vital capacity (VC) was measured in 483 and 387
      volunteers in the year 1982 and 2004 respectively; peak expiratory flow rate
      (PEFR) was measured in 200 and 388 subjects in the year 1982 and 2004
      respectively. Both VC and PEFR were found to be reduced in the year 2004 as
      compared to those measured in 1982 from the similar population matched for age
      groups. They were significantly (P<0.001) lower (20-23% less for VC and 4-14%
      less for PEFR) in the 20-30 years age group. There was also significant (P<0.05)
      decrease in PEFR for the population of 16-19 years age group studied in 2004
      compared to that of 1982. Significant (P<0.001) deterioration in VC per meter of
      height was observed in the population above 20 years of age. The mean values of
      VC (ml/m height) ranging from 2119.27 +/- 316.64 (20-25 years age group) to
      1923.29 +/- 225.43 (40-50 years age group) in 1982 have dropped to 1896.54 +/-
      289.50 and 1593.64 +/- 419.36 for the respective age groups in 2004. Similarly,
      mean value of PEFR (L/ min) was found to be reduced from 523.67 +/- 64.69 in 1982
      to 471.44 +/- 85.25 in 2004 for the same age groups of 20-25 years. Similar
      reduction was also recorded for 16-19 yr group and 26-30 yr group of population.
      Air-pollution and sedentary lifestyles in the population of this city may be
      probable reasons for the decline in respiratory performance.

PMID- 18341222
TI  - The effects of carbamazepine on sperm morphology in wistar rats.
AB  - Carbamazepine (5 H-dibenz (b, f) azepine-5-carboxamide), is an antiepileptic drug
      which is expected to be administered regularly over a substantial part of
      patients lifetime. As the gender focus in epilepsy the later years has primarily
      been on women, there certainly is a lack of studies focused on the effects
      particular to men. The present study was aimed to investigate its effects on germ
      cell's by employing the sperm morphology assay. Twelve groups of male wistar rats
      were treated with sterile water 0.5 ml, cyclophosphamide (CP) 20 mg/kg,
      carbamazepine 9, 18, 36 mg/kg (i.p) and 2% gumacasia 0.25 ml/100 g respectively
      for 5 consecutive days at intervals of 24 hrs. Following the last exposure, on
      days 14 and 35 sperm morphology assay was conducted as per the standard
      procedure. Mann-Whitney 'U' test was used for statistical analysis and the level
      of significance was P<0.01. Neither carbamazepine nor cyclophosphamide induced
      formation of abnormally shaped sperms at 14 day time interval. Whereas on day 35,
      with 18 mg/kg dose level of carbamazepine there was an increase in the number of
      sperms with heads defects (P<0.01); Whereas in the other two dose levels the
      number of abnormally shaped sperms had decreased. 2% gumacasia increased the
      number of sperms with tail defects at day 35. (Mann-Whitney 'U' test).
      CONCLUSION: Carbamazepine and 2% gumacasia could be germ cell mutagens and could
      cause infertility on prolonged use therefore further studies with serum drug
      level estimations are needed.

PMID- 18341223
TI  - The medial septum acts through the medial preoptic area for thermoregulation and
      works with it for sleep regulation.
AB  - The chronic changes in sleep-wakefulness (S-W), body temperature (Tb), locomotor
      activity (LMA) and thermal preference were studied in male Wistar rats after the
      destruction of neurons in both the medial preoptic area (mPOA) and the medial
      septum (MS) by intracerebral injection of N-methyl-D-aspartic acid. An increase
      in the Tb, and a preference for higher ambient temperature (Tamb) of 30 degrees C
      were observed after the combined lesion of the mPOA and the MS. Similar changes
      were reported to occur after the lesion that was restricted to the mPOA. But
      these alterations were in contrast to the decrease in Tb and preference for lower
      Tamb, observed after the MS lesion. The thermostat of the brain would have been
      reset at a higher level after the combined lesion, as there was an increase in
      Tb, along with a preference for a higher Tamb, and an increase in LMA. There was
      a reduction in the frequency and the duration of the slow wave sleep (SWS)
      episodes, and a reduction in the frequency of the paradoxical sleep (PS) episodes
      after the combined lesion. The destruction of the MS neurons was probably
      responsible for the reduction in the frequency of SWS, whereas the loss of mPOA
      neurons was responsible for the decrease in the duration of SWS and frequency of
      PS. It can be suggested that the MS exerts its influence on thermoregulation
      through the mPOA. However, the MS and the mPOA seem to play independent, but
      complementary roles in sleep promotion.

PMID- 18341224
TI  - Investigation on the effect of eclipta alba on animal models of learning and
      memory.
AB  - Short and long term memory loss may result from deteriorating cerebral mechanisms
      due to varied causes which could have a tremendous impact on the quality of life.
      Herbs are being constantly explored to resolve cognitive deficits. Eclipta alba
      (Ea) commonly called as the trailing Eclipta is being examined for its memory
      enhancing quality as it is traditionally used for this purpose. The shade dried
      leaves of Eclipta alba was extracted with distilled water. The suspension of Ea
      containing 100 and 200 mg/kg was administered to rats to evaluate Transfer
      Latency (TL) on an elevated plus maze. TL was a measure of acquisition and
      retrieval learning. Mice were placed at the center of open field apparatus to
      assess spatial habitual learning, observed for 20 minutes for rearing and time
      spent during rearing using varied doses for 30 minutes, 24 hours and 96 hours and
      144 hrs. The results revealed significant improvement of retrieval memory.

PMID- 18341225
TI  - Effect of exercise on rate pressure product in premenopausal and postmenopausal
      women with coronary artery disease.
AB  - Incidence of coronary artery disease (CAD) increases sharply after menopause in
      women. Rate pressure product (RPP) is a major determinant of cardiac oxygen
      consumption. It is an important indicator of ventricular function. RPP varies
      with exercise. The peak rate pressure product (PRPP) which gives an accurate
      reflection of the myocardial oxygen demand and myocardial workload is the RPP at
      peak of exercise. The higher the PRPP, the more will be myocardial oxygen
      consumption (MVO2). The ability to reach higher PRPP is associated with more
      adequate coronary perfusion. Thus the low value of PRPP suggests significant
      compromise of coronary perfusion and decreased left ventricular function. In the
      present study effect of exercise on RPP of pre and postmenopausal women with CAD
      was compared. The percentage increase in RPP was significantly more in
      postmenopausal women with CAD (62%) as compared to premenopausal women with CAD
      (54%) indicating more compromised coronary perfusion in postmenopausal women.

PMID- 18341226
TI  - Status of lipid peroxidation, glutathione, ascorbic acid, vitamin E and
      antioxidant enzymes in patients with pregnancy--induced hypertension.
AB  - The exact pro-oxidant and antioxidant status in pregnancy--induced hypertension
      patients is still not clear. To add a new insight to the question, changes in the
      erythrocyte lipid peroxidation products (malondialdehyde; MDA), levels of
      glutathione (GSH), ascorbic acid and plasma vitamin E (non enzymatic antioxidant
      parameters) and activities of antioxidant enzymes superoxide dismutase (SOD),
      glutathione peroxidase (GPx), catalase in erythrocytes were studied in thirty
      five patients with pregnancy--induced hypertension and thirty five healthy
      pregnant normotensive cases. It was observed that there was a significant
      increase in erythrocyte MDA levels, activities of SOD, GPx and a significant
      decrease in erythrocyte GSH, ascorbic acid, plasma vitamin E levels and catalase
      activity in patients with pregnancy--induced hypertension when compared to
      controls. The results of our study have shown higher oxygen free radical
      production, evidenced by increased levels of MDA and decreased levels of GSH,
      ascorbic acid, vitamin E and Catalase activity supports the oxidative stress in
      pregnancy--induced hypertension. The increased activities of antioxidant enzymes
      may be a compensatory regulation in response to increased oxidative stress. The
      decreased concentrations of glutathione and antioxidant vitamin status supports
      the hypothesis that lipid peroxidation is an important causative factor in the
      pathogenesis of preeclampsia.

PMID- 18341227
TI  - Status of lipid peroxidation and plasma iron level in bronchial asthmatic
      patients.
AB  - Low antioxidant levels and oxidative stress due to airway inflammation may be
      determinant of asthma severity. The study was conducted to find the extent of
      lipid peroxidation and change in the levels of plasma iron in asthmatic patients
      with severity of disease. Study included 155 asthmatic and 156 healthy volunteers
      of the age groups 18-45 of either sex. Asthmatic patients were grouped into mild,
      moderate and severe groups on the basis of Forced Expiratory Volume in first
      second percent (FEV1%). Level of plasma malondialdhyde (MDA) was used as index of
      lipid peroxidation. A significant increase (P<0.01) in plasma MDA and plasma iron
      levels was found in asthmatic subjects as compared to controls. There was maximum
      increase in plasma MDA and iron levels in moderate asthmatic group. A positive
      correlation between plasma MDA and iron (r = +0.3) has been found in asthmatic
      patients. An increased plasma iron levels in asthmatics may contribute to
      aggravate lipid peroxidation.

PMID- 18341228
TI  - Correlation of antioxidants and fitness levels in undergraduate medical students.
AB  - Fitness is the ability of the organism to maintain the various internal
      equilibriums as closely as possible to the resting state during strenuous
      exercise and to restore promptly after exercise. The aim of the present study was
      to evaluate the fitness and correlate it with anti-oxidant levels of 50 male
      medical students in the age group of 18 to 25 years. Fitness was assessed by
      Harvard Step Test. The antioxidant status was assessed by Vitamin C and Vitamin E
      levels in the blood. Three groups were formed on the basis of fitness score. The
      mean values of fitness scores were 95.33 +/- 7.66, 68.5 +/- 9.22 and 37 +/- 10.9,
      in-group A, B and C, respectively. Between the three groups, Vitamin E values
      were significantly different but not the Vitamin C levels. Thus, it is concluded
      that Vitamin E levels influence the fitness state of an individual.

PMID- 18341229
TI  - A study to compare the effectiveness of GSR biofeedback training and progressive
      muscle relaxation training in reducing blood pressure and respiratory rate among
      highly stressed individuals.

PMID- 18341230
TI  - Phosphate transport by the everted intestinal and gallbladder sacs of the frog.

PMID- 18341231
TI  - R-R variability from standard 12 lead ECG may be useful for assessment of
      autonomic nervous function.

PMID- 18341232
TI  - Measuring the value of nonwage employee benefits: building a model of the
      relation between benefit satisfaction and value.
AB  - Researchers have commonly assumed benefits that employees view as more valuable
      have a greater influence on their attitudes and behaviors. Researchers have used
      2 common methods to measure benefit value: attaching a monetary value to benefits
      and using self-reports of benefit importance. The present authors propose that
      the 2 approaches are conceptually distinct and have different implications. They
      use a social exchange perspective to justify this distinction and integrate both
      approaches and benefit satisfaction into a more comprehensive model of benefit
      perception. Results suggest that both measures have practical applications
      depending on the nature of the exchange relationship between the organization and
      employees. However, this relationship depends on the specific benefit and on
      employee satisfaction with that benefit. Some benefits lend themselves to a
      monetary estimate, whereas others lend themselves more to a nonmonetary
      valuation.

PMID- 18341233
TI  - Psychologists versus psychologists: evaluating the claims of psychologists who
      publicly criticize their profession.
AB  - Since the 1990s, 7 psychologists have written books for a public audience
      expressing great dissatisfaction with mental health practitioners. These critics
      represent 4 English-speaking countries: Australia, Canada, the United Kingdom,
      and the United States. Those psychologists make 3 basic arguments: (a) any
      improvements attributed to psychotherapy are due to placebo effect, (b)
      psychological assessments have little value, and (c) clinicians do not meet the
      legal standards to qualify as experts in a court of law. The present author
      examines these arguments and concludes that these concerns are unfounded. The
      exception is that several forensic psychologists had been using tests that were
      invalid for legal purposes, but this situation has shown gradual improvement in
      the past 15 years.

PMID- 18341234
TI  - Creativity, intelligence, and personality: a critical review of the scattered
      literature.
AB  - The authors examined the relations among intelligence, personality, and
      creativity. They consider the concept and definition of creativity in conjunction
      with the qualifications that researchers in the field have suggested. The present
      authors briefly refer to historiometric studies but focus on psychometric
      intelligence and its relations to tests of divergent thinking (DT) and ratings of
      creativity. The authors consider the relation between personality and creativity
      in the context of Eysenckian 3-factor and 5-factor models of personality and with
      reference to DT tests and ratings of creativity. The authors also present
      recommendations for the future study of creativity.

PMID- 18341235
TI  - Using epistemic ratios to evaluate hypotheses: an imprecision penalty for
      imprecise hypotheses.
AB  - According to Bayesians, the null hypothesis significance-testing procedure is not
      deductively valid because it involves the retention or rejection of the null
      hypothesis under conditions where the posterior probability of that hypothesis is
      not known. Other criticisms are that this procedure is pointless and encourages
      imprecise hypotheses. However, according to non-Bayesians, there is no way of
      assigning a prior probability to the null hypothesis, and so Bayesian statistics
      do not work either. Consequently, no procedure has been accepted by both groups
      as providing a compelling reason to accept or reject hypotheses. The author aims
      to provide such a method. In the process, the author distinguishes between
      probability and epistemic estimation and argues that, although both are important
      in a science that is not completely deterministic, epistemic estimation is most
      relevant for hypothesis testing. Based on this analysis, the author proposes that
      hypotheses be evaluated via epistemic ratios and explores the implications of
      this proposal. One implication is that it is possible to encourage precise
      theorizing by imposing a penalty for imprecise hypotheses.

PMID- 18341236
TI  - Systematic reviews: I. The correlation between laboratory tests on marginal
      quality and bond strength. II. The correlation between marginal quality and
      clinical outcome.
AB  - PURPOSE: An accepted principle in restorative dentistry states that restorations
      should be placed with the best marginal quality possible to avoid postoperative
      sensitivity, marginal discoloration, and secondary caries. Different laboratory
      methods claim to predict the clinical performance of restorative materials, for
      example, tests of bond strength and microleakage and gap analysis. The purpose of
      this review was twofold: (1) find studies that correlated the results of bond
      strength tests with either microleakage or gap analysis for the same materials,
      and (2) find studies that correlated the results of microleakage and/or gaps with
      the clinical parameters for the same materials. Furthermore, influencing factors
      on the results of the laboratory tests were reviewed and assessed. MATERIALS AND
      METHODS: For the first question, searches for studies were conducted in the
      MEDLINE database and IADR/AADR abtracts online with specific search and inclusion
      criteria. The outcome for each study was assessed on the basis of the statistical
      test applied in the study, and finally the number of studies with or without
      correlation was compiled. For the second question, results of the quantitative
      marginal analysis of Class V restorations published by the University of Zurich
      with the same test protocol and prospective clinical trials were searched that
      investigated the same materials for at least 2 years in Class V cavities. Pearson
      correlation coefficients were calculated for pooled data of materials and
      clinical outcome parameters such as retention loss, marginal discoloration,
      marginal integrity, and secondary caries. For the correlation of dye penetration
      and clinical outcome, studies on Class V restorations published by the same
      research institute were searched in MEDLINE that examined the same adhesive
      systems as the selected clinical trials. RESULTS: For the correlation bond
      strength/microleakage, 30 studies were included into the review, and for the
      correlation bond strength/gap analysis 18 studies. For both topics, about 80% of
      the studies revealed that there was no correlation between the two methods. For
      the correlation quantitative marginal analysis/clinical outcome, data were
      compared to the clinical outcome of 11 selected clinical studies. In only 2 out
      of the 11 studies (18%) did the clinical outcome match the prognosis based on the
      laboratory tests; the remaining studies did not show any correlation. When
      pooling data on 20 adhesive systems, no correlation was found between the
      percentage of continuous margin of restorations placed in extracted premolars and
      the percentage of teeth that showed no retention loss in clinical studies, no
      discoloured margins, acceptable margins, or absence of secondary caries. With
      regard to the correlation of dye penetration and clinical studies, no sufficient
      number of studies was found that matched the inclusion criteria. However,
      literature data suggest that there is no correlation between microleakage data as
      measured in the laboratory and clinical parameters. CONCLUSION: The results of
      bond strength tests did not correlate with laboratory tests that evaluated the
      marginal seal of restorations such as microleakage or gap analysis. The
      quantitative marginal analysis of Class V fillings in the laboratory was unable
      to predict the performance of the same materials in vivo. Therefore, microleakage
      tests or the quantitative marginal analysis should be abandoned and research
      should focus on laboratory tests that are validated with regard to their ability
      to satisfactorily predict the clinical performance of restorative materials.

PMID- 18341237
TI  - Marginal integrity: is the clinical performance of bonded restorations
      predictable in vitro?
AB  - PURPOSE: In vitro testing of dental materials is daily routine for the
      preclinical investigation of restoratives. Although clinical trials remain the
      ultimate instrument, preclinical screenings are still important. However, it is
      still not fully understood whether clinical performance is predictable in the
      lab. The aim of this paper is to combine known facts and recent results to answer
      the question concerning in vitro predictability of clinical marginal integrity
      and related outcome. MATERIALS AND METHODS: (a) The literature in the field from
      1990-2005 was analyzed regarding marginal integrity in vitro and in vivo,
      especially in frequently cited papers. (b) Five different adhesives, a 4-step
      etch-and-rinse adhesive (Syntac), a 3-step etch-and-rinse adhesive (OptiBond FL),
      a 2-step etch-and-rinse adhesive (Single Bond), a 2-step self-etching adhesive
      (Clearfil SE Bond), and a 1-step self-etching adhesive (Xeno III) were used for
      bonding of a resin composite (Tetric Ceram) in Class I cavities (n = 8 in vitro
      and n = 8 in vivo). In vitro, the restorations were thermomechanically loaded
      (TML; 100,000 with 50 N and 2500 cycles of 5 degrees C/55 degrees C) according to
      a previously published protocol. Replicas of restorations were analyzed initially
      and after TML (in vitro) and two years of clinical service (respectively).
      RESULTS: (a) Marginal integrity is reliably predictable in laboratory in vitro
      studies by simulating clinical circumstances. However, marginal analyses of
      direct restorations in vitro still suffer from not being able to determine a
      lower boderline, ie, actually worse in vitro results may still result in
      acceptable restorations in vivo. (b) The in vitro-in vivo comparison revealed
      significantly better marginal adaptation in (enamel) margins when etch-and-rinse
      adhesives were used for bonding. After 2 years of clinical service, restorations
      bonded with self-etching adhesives did not clinically fail but exhibited
      significantly more marginal gaps. CONCLUSION: Clinical behavior of restoration
      margins is predictable. However, marginal adaptation is only one among several
      important aspects in restorative dentistry, ie, clinical outcome is not
      predictable from marginal integrity alone.

PMID- 18341238
TI  - Prediction of clinical outcomes of a restoration based on in vivo marginal
      quality evaluation.
AB  - The question "Does initial marginal quality of composite restorations have any
      affect on clinical longevity?" is posed and evidence presented to attempt to
      provide an answer. This paper examines the literature on what is known regarding
      the rates and causes of failure of restorations, clinical evaluation of
      restoration outcomes and marginal quality, the relationship between marginal
      quality and secondary caries, and the relationship of polymerization shrinkage
      and clinical failures. The most frequently reported cause for restoration
      replacement is secondary caries. The evidence that poor marginal quality promotes
      or is the primary cause for secondary caries is limited and indicates that any
      direct relationship is unlikely. There is evidence that secondary caries is
      related to the bacterial composition of marginal plaque, and that this and oral
      hygiene are the primary factors in disease initiation. Evidence also exists that
      dentists vary in their diagnoses of secondary caries and that except in the
      presence of frank secondary caries, it is not possible to diagnose secondary
      caries with high sensitivity and specificity based on visual and tactile
      examination of restoration margins. Marginal gaps created by polymerization
      shrinkage do not appear to increase the risk for secondary caries, but can lead
      to marginal staining. Initial marginal quality should not affect longevity, as it
      does not necessarily increase the risk of secondary caries. However, poor
      marginal quality is, in fact, likely to decrease clinical longevity due to the
      misdiagnosis of secondary caries.

PMID- 18341239
TI  - Recommendations for conducting controlled clinical studies of dental restorative
      materials. Science Committee Project 2/98--FDI World Dental Federation study
      design (Part I) and criteria for evaluation (Part II) of direct and indirect
      restorations including onlays and partial crowns.
AB  - About 35 years ago, Ryge provided a practical approach to the evaluation of the
      clinical performance of restorative materials. This systematic approach was soon
      universally accepted. While that methodology has served us well, a large number
      of scientific methodologies and more detailed questions have arisen that require
      more rigor. Current restorative materials have vastly improved clinical
      performance, and any changes over time are not easily detected by the limited
      sensitivity of the Ryge criteria in short-term clinical investigations. However,
      the clinical evaluation of restorations not only involves the restorative
      material per se but also different operative techniques. For instance, a
      composite resin may show good longevity data when applied in conventional
      cavities but not in modified operative approaches. Insensitivity, combined with
      the continually evolving and nonstandard investigator modifications of the
      categories, scales, and reporting methods, has created a body of literature that
      is extremely difficult to interpret meaningfully. In many cases, the
      insensitivity of the original Ryge methods leads to misinterpretation as good
      clinical performance. While there are many good features of the original system,
      it is now time to move on to a more contemporary one. The current review
      approaches this challenge in two ways: (1) a proposal for a modern clinical
      testing protocol for controlled clinical trials, and (2) an in-depth discussion
      of relevant clinical evaluation parameters, providing 84 references that are
      primarily related to issues or problems for clinical research trials. Together,
      these two parts offer a standard for the clinical testing of restorative
      materials/procedures and provide significant guidance for research teams in the
      design and conduct of contemporary clinical trials. Part 1 of the review
      considers the recruitment of subjects, restorations per subject, clinical events,
      validity versus bias, legal and regulatory aspects, rationales for clinical trial
      designs, guidelines for design, randomization, number of subjects,
      characteristics of participants, clinical assessment, standards and calibration,
      categories for assessment, criteria for evaluation, and supplemental
      documentation. Part 2 of the review considers categories of assessment for
      esthetic evaluation, functional assessment, biological responses to restorative
      materials, and statistical analysis of results. The overall review represents a
      considerable effort to include a range of clinical research interests over the
      past years. As part of the recognition of the importance of these suggestions,
      the review is being published simultaneously in identical form in both the
      Journal of Adhesive Dentistry and Clinical Oral Investigations. Additionally, an
      extended abstract will be published in the International Dental Journal, giving a
      link to the web full version. This should help to introduce these considerations
      more quickly to the scientific community.

PMID- 18341240
TI  - Empire matters: implications for pastoral care.
AB  - In this essay, I argue that the American Empire matters for pastoral care. I
      begin with a discussion of the meaning of empire and the particular historical
      roots and characteristics of the American Empire. From this, I contend that the
      American Empire matters because the United States has had a long history of
      expansionist aims, which has been couched in idealized secular discourse as well
      as ensconced in theo-political discourse. These discourses, which have,
      implicitly or explicitly, supported foreign policies and actions aimed at
      political, economic, and military dominion, are joined to an empire psyche. This
      empire psyche and the actions of U.S. governments are matters for pastoral care
      because of a) the various physical, psychological, and spiritual harms that
      attend hubris, greed, entitlement, and the quest for hegemony, and b) the
      theological contradictions inherent in Christian discourse that supports the
      American Empire. These consequences and contradictions serve as reasons why
      pastoral theologians and caregivers ought to bring these matters to public
      reflection and conversation. I conclude with a brief depiction of possible
      pastoral actions given the reality of the American Empire.

PMID- 18341241
TI  - Patient profiles in psoriatic disease: a case-based approach.
AB  - Psoriasis and psoriatic arthritis are related conditions that can have numerous
      untoward consequences. Moreover, appropriate management of these conditions can
      be challenging, as each affected patient has unique needs that must be addressed.
      With that in mind, the authors discuss three real-life cases, highlighting
      principles that may facilitate the effective case-by-case management of psoriatic
      disease.

PMID- 18341242
TI  - New landscape of type 2 diabetes management.

PMID- 18341243
TI  - Beyond glycemic control: the role of incretin hormones.

PMID- 18341244
TI  - Clinical pearls and strategies to optimize patient outcomes.

PMID- 18341245
TI  - Quantitative structure-activity relationship study of ATP-sensitive potassium
      channel openers: derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1
      dioxide.
AB  - The inhibitory activity of glucose-induced insulin secretion on isolated rat
      pancreatic islets and the contractile activity of KCl-depolarized rat aorta rings
      of the derivatives of 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxide are
      quantitatively analyzed using multiple regression analysis. The study has helped
      to ascertain the role of different substituents in explaining these observed
      inhibitory activities. From a derived most significant correlation equation, it
      was concluded that a less hydrophobic 3-substituent and a less bulky 7
      substituent in addition to a 3-aminoisopropyl and a 6-chloro substituent are
      advantageous to enhance the inhibitory action of a compound towards rat
      pancreatic islets. On the other hand, the more hydrophobic 6- and 7-substituents
      augment the contractile activity. The analysis, in this way, provided the grounds
      for rationalizing the substituent selection in designing the improved potency
      compounds in the series.

PMID- 18341246
TI  - Kinetic analysis of urea-inactivation of beta-galactosidase in the presence of
      galactose.
AB  - The effect of galactose on the inactivation of purified beta-galactosidase from
      the black bean, Kestingiella geocarpa, in 5 M urea at 50 degrees C and at pH 4.5,
      was determined. Lineweaver-Burk plots of initial velocity data in the presence
      and absence of urea and galactose were used to determine the relevant K(m) and
      V(max) values, with p-nitrophenyl beta-D-galactopyranoside (PNPG) as substrate,
      S. The inactivation data were analysed using the Tsou equation and plots. Plots
      of ln([P](infinity) - [P](t) ) against time in the presence of urea yielded the
      inactivation rate constant, A. Plots of A vs [S] at different galactose
      concentrations were zero order showing that A was independent of [S]. Plots of
      [P](infinity) vs [S] were used to determine the mode of inhibition of the enzyme
      by galactose, and slopes and intercepts of the 1/[P](infinity) vs. 1/[S] yielded
      k(+0) and k '(+0), the microscopic rate constants for the free enzyme and the
      enzyme-substrate complex, respectively. Plots of k(+0) and k '(+0) vs. galactose
      concentrations showed that galactose protected the free enzyme and not the enzyme
      substrate complex against urea inactivation via a noncompetitive mechanism at low
      galactose concentrations and a competitive pattern of inhibition at high
      galactose concentrations. The implication of the different modes of inhibition in
      protecting the free enzyme was discussed.

PMID- 18341247
TI  - pH-dependent inhibition of mushroom tyrosinase by N-substituted N
      nitrosohydroxylamines.
AB  - Several synthetic N-substituted N-nitrosohydroxylamines were found to inhibit
      mushroom tyrosinase in a pH-dependent manner regardless of the N-substituent. The
      inhibitory activity, or pI(50) ( - log [IC(50), M]) value, linearly decreased as
      the pH of the media increased. The inhibitory activities of tested N-substituted
      N-nitrosohydroxylamines at pH 6.8 and 5.8 were found to be almost 10 times and
      100 times greater than at pH 7.8, respectively. The types of inhibition were
      different at pH 6.8 and 5.8. These results suggest that the inhibitory effect of
      N-substituted N-nitrosohydroxylamines is caused by the non-ionized form of the
      inhibitor. Furthermore, the mechanism of inhibition depends on the interaction
      between the inhibitor and the active site of tyrosinase at different pH values.

PMID- 18341248
TI  - Irreversible inhibition of aldolase by a phosphorylated alpha-dicarbonyl
      compound.
AB  - The preparation of a phosphorylated alpha-dicarbonyl compound designed to
      specifically react with arginine residues of enzymes accepting phosphorylated
      compounds as effectors is reported, and shown to inhibit rabbit muscle aldolase
      in a time-dependent and irreversible manner. This irreversible inhibition occured
      in a buffer devoid of borate ions, suggesting that the presence of the phosphate
      moiety contributes in the stabilization of the adduct formed with arginine
      residues. Under the same conditions, the metalloenzyme iron superoxide dismutase,
      in which an arginine is known to be critical for the catalytic function, is not
      significantly inhibited.

PMID- 18341249
TI  - In-vitro evaluation of selected chalcones for antioxidant activity.
AB  - Synthetic chalcones (SCs) having different side chains on the 1-(2-Hydroxy-3-(2
      hydroxy-cyclohexyl)-4,6 dimethoxy-phenyl(-methanone structure were examined in
      vitro for their antioxidant abilities by DPPH (2,2-diphenyl-1-picryl hydrazine)
      radical scavenging activity, reducing ability, OH radical scavenging activity,
      inhibition of polyphenol oxidase (PPO) and formation of diene conjugates.
      Overall, with few exceptions, all the SCs showed moderate biological activity in
      all the parameters examined. The SCs were found to be reactive towards DPPH
      radical and had considerable reducing ability. With few exceptions, all the test
      compounds under study were found to possess moderate to poor OH radical
      scavenging activity and inhibited PPO significantly and all were found to be
      effective inhibitors of hydroperoxide formation. These findings suggest that
      these SCs can be considered as potential antioxidant agents which might be
      further explored for the design of lead antioxidant drug candidates.

PMID- 18341250
TI  - In vitro inhibition of cytosolic carbonic anhydrases I and II by some new
      dihydroxycoumarin compounds.
AB  - A new series of 6, 7-dihydroxy-3-(methylphenyl) chromenones, including three new
      derivatives, i.e. 6,7-dihydroxy-3-(2-methylphenyl)-2H-chromen-2-one (OPC); 6,7
      dihydroxy-3-(3-methylphenyl)-2H-chromen-2-one (MPC); 6,7-dihydroxy-3-(4
      methylphenyl)-2H-chromen-2-one (PPC) and one previously described, namely 6,7
      dihydroxy-3-phenyl-2H-chromen-2-one (DPC), were synthesized. These compounds were
      investigated as inhibitors of human carbonic anhydrase I (hCA-I) and human
      carbonic anhydrase II (hCA-II) which had been purified from human erythrocytes on
      an affinity gel comprised of L-tyrosine-sulfonamide-Sepharose 4B.

PMID- 18341251
TI  - Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors.
AB  - Some novel fused heterocyclic compounds of 2, 5-disubstituted-benzoxazole and
      benzimidazole derivatives, which were previously synthesized by our group, were
      investigated for their inhibitory activity on both eukaryotic DNA topoisomerase I
      and II in a cell free system. 2-Phenoxymethylbenzimidazole (17), 5-amino-2-(p
      fluorophenyl)benzoxazole (3), 5-amino-2-(p-bromophenyl)benzoxazole (5), 5-nitro-2
      phenoxymethyl-benzimidazole (18), 2-(p-chlorobenzyl)benzoxazole (10) and 5-amino
      2-phenylbenzoxazole (2) were found to be more potent as eukaryotic DNA
      topoisomerase I poisons than the reference drug camptothecin having IC(50) values
      of 14.1, 132.3, 134.1, 248, 443.5, and 495 microM, respectively. 5-Chloro-2-(p
      methylphenyl)benzoxazole (4), 2-(p-nitrobenzyl)benzoxazole (6) and 5-nitro-2-(p
      nitrobenzyl)benzoxazole (8) exhibited significant activity as eukaryotic DNA
      topoisomerase II inhibitors, having IC(50) values of 22.3, 17.4, 91.41 microM,
      respectively, showing higher potency than the reference drug etoposide.

PMID- 18341252
TI  - Synthesis and biological evaluation of novel angular fused Pyrrolocoumarins.
AB  - Angular pyrrolocoumarins were synthesized from the reaction of 4-hydroxyindole or
      5-hydroxyindole with DMAD and PPh(3) and were tested for anti-inflammatory and
      antioxidant activity. These compounds significantly inhibited the carrageenin
      induced paw edema (60.5%-73.4%) and have important scavenging activity. Although
      their interaction with the free stable radical DPPH is not high, compound 9 is
      the most potent (73.4%) in the in vivo experiment. Compound 7 seems to be a
      potent LOX inhibitor. An attempt was made to correlate the biological results
      with their structural characteristics and physicochemical parameters.

PMID- 18341253
TI  - Quantitative structure-activity relationship study of novel rhinacanthins and
      related naphthoquinone esters as anticancer agents.
AB  - The anticancer activity of rhinacanthins and related naphthoquinone esters is
      quantitatively analyzed through Fujita-Ban and Hansch approaches. The analyses
      have helped to ascertain the role of different substituents in explaining the
      observed inhibitory actions of these compounds. From both approaches it appeared
      that naphthalene ring instead of benzene ring, dimethyl substitution at R(1) and
      R(2), and hydrogen-bond acceptor substituents at R(3) (Figure 1) are advantageous
      to improve the activity of a compound against KB cell lines. This in turn leads
      to the suggestion that the rhinacanthin-N scaffold is the structural entity that
      needs exploration for new potential compounds. Further, in the Fujita-Ban
      analysis, it is observed that the compounds bearing a OMe substitution, relative
      to H, at R(4) have a slight positive contribution to pIC(50) (KB) whereas the
      substituents H or OMe at R(5), relative to OH, have negative contributions. In
      conformity with these findings, the Hansch approach revealed that a more
      hydrophobic group at R(4) and a more hydrophilic group at R(5) positions are
      beneficial in raising the activity. The two quantitative structure-activity
      relationship (QSAR) analyses, differing in parametric approach, therefore,
      provided the grounds for rationalizing the substituent selection to design more
      potent compounds of the series.

PMID- 18341254
TI  - 6-Azathymidine-4'-thionucleosides: synthesis and antiviral evaluation.
AB  - The synthesis of dideoxy-6-azathymidine 4'-thionucleoside 1-(2,3-dideoxy-4-thio
      beta-D-erythro-pentofuranosyl)-(6-azathymidine) (2), and the L-nucleoside, 1-(4
      thio-beta-L-erythro-pentofuranosyl)-(6-azathymidine) (3) and their evaluation
      against a wide panel of antiviral assays are described. The L-thionucleoside (3)
      was devoid of antiviral activity. The dideoxy-thionucleoside (2) was moderately
      active against vaccinia virus (VV) and the herpes simplex virus strains HSV-1
      (strain KOS) and HSV-2 (strain G) (MIC 12 microM) and retained inhibitory
      activity vs a thymidine kinase-deficient strain HSV-1/TK(-), suggesting that (2)
      is not dependent on viral TK-catalysed phosphorylation for antiviral activity
      and/or may use an alternative metabolic activation pathway.

PMID- 18341255
TI  - Mild and efficient synthesis of new tetraketones as lipoxygenase inhibitors and
      antioxidants.
AB  - A mild and efficient route to tetraketones (2-22) has been developed by way of
      tetraethyl ammonium bromide (Et(4)N(+)Br(- )) mediated condensation of dimedone
      (5,5-dimethylcyclohexane-1,3-dione, 1) with a variety of aldehydes. All these
      compounds showed significant lipoxygenase inhibitory activity and moderate to
      strong antioxidant potential. Compounds 19 (IC(50) = 7.8 microM), 22 (IC(50) =
      12.5 microM), 3 (IC(50) = 16.3 microM), 11 (IC(50) = 17.5 microM) and 8 (IC(50) =
      21.3 microM) showed significant inhibitory potential against lipoxygenase
      (baicalein, IC(50) = 22.4 microM). On the other hand compound 19 (IC(50) = 33.6
      microM) also showed strong antioxidant activity compared to the standard (IC(50)
      = 44.7 microM). This study is likely to lead to the discovery of therapeutically
      efficient agents against very important disorders including inflammation, asthma,
      cancer and autoimmune diseases.

PMID- 18341256
TI  - Synthesis of monooxime-monocarbamoyl bispyridinium compounds bearing (E)-but-2
      ene linker and evaluation of their reactivation activity against tabun- and
      paraoxon-inhibited acetylcholinesterase.
AB  - Six AChE monooxime-monocarbamoyl reactivators with an (E)-but-2-ene linker were
      synthesized using modification of currently known synthetic pathways. Their
      potency to reactivate AChE inhibited by the nerve agent tabun and insecticide
      paraoxon was tested in vitro. The reactivation efficacies of pralidoxime, HI-6,
      obidoxime, K048, K075 and the newly prepared reactivators were compared.
      According to the results obtained, one reactivator seems to be promising against
      tabun-inhibited AChE and two reactivators against paraoxon-inhibited AChE. The
      best results were obtained for bisquaternary substances with at least one oxime
      group in position four.

PMID- 18341257
TI  - Synthesis and in vitro antimicrobial studies of some new 3-[phenyldiazenyl]
      benzaldehyde N-phenyl thiosemicarbazones.
AB  - The increasing clinical importance of drug resistant microbial pathogens has lent
      additional urgency to microbiological research and new antimicrobial compound
      development. For this purpose, a new series of 3-[phenyldiazenyl] benzaldehyde N
      phenylthiosemicarbazones were synthesized and evaluated for antifungal and
      antibacterial activity. The reaction of 2-hydroxy-5-[phenyldiazenyl] benzaldehyde
      (I) with N-phenylhydrazinecarbothioamide (II) were carried out in DMF. The
      antimicrobial activity of the synthesized target compounds (III) were evaluated
      by screening on different human pathogens using the disc diffusion assay. All the
      compounds exhibited considerable inhibition against the bacteria and fungi
      tested.

PMID- 18341258
TI  - A novel synthesis and antimicrobial activity of 1-[(Substituted-phenyl)
      sulfonyl]pyrrolidin-2-ones.
AB  - Novel cyclization of 4-(substituted-phenylsulfonamido)butanoic acids to their
      corresponding 1-[(substituted-phenyl)sulfonyl]pyrrolidin-2-ones was successfully
      achieved by using polyphosphate ester (PPE). The reaction time was considerably
      reduced with corresponding increase in the yields, when polyphosphate ester (PPE)
      was used in combination with 4-(N,N-dimethylamino)pyridine (DMAP). All the
      synthesized compounds were screened for their antimicrobial activity. Minimum
      Inhibitory Concentration (MIC) values of synthesized compounds were also
      determined, and were found to be in the range of 0.09-1.0 mg.

PMID- 18341259
TI  - Three components coupling catalysed by NaHSO(4).Sio(2) - a convenient synthesis,
      antibacterial and antifungal activities of novel 6-Aryl-1,2,4,5-tetrazinan-3
      ones.
AB  - A novel method has been developed for the synthesis of 6-aryl-1,2,4,5-tetrazinan
      3-ones through a one-pot reaction of urea, various substituted aromatic
      benzaldehyde having electron donating and electron withdrawing groups and
      ammonium acetate in the presence of reusable NaHSO(4).SiO(2) heterogeneous
      catalyst in dry media under microwave irradiation. FT-IR, (1)H NMR, D(2)O
      Exchange, (13)C NMR, Heteronuclear Single Quantum Correlation (HSQC) spectra, MS
      and elemental analysis characterized all the synthesized compounds. In vitro
      antibacterial/fungal activities were evaluated for six new compounds. The
      antibacterial studies revealed that compounds 1-6 had better activity against
      tested Gram-positive and Gram-negative organisms. Compounds 1 and 5 were more
      active against beta-Heamolytic streptococcus, a Gram-positive bacteria and
      Pseudomonas, a Gram-negative bacteria, respectively, than the standard drug
      ciprofloxacin. Besides, of all the compounds tested, compound 5 was more
      effective against Aspergillus flavus, a fungal strain than the standard drug
      fluconazole.

PMID- 18341260
TI  - Targeting human DNA polymerase alpha for the inhibition of keratinocyte
      proliferation. Part 1. Homology model, active site architecture and ligand
      binding.
AB  - In order to understand the binding modes of human DNA polymerase alpha (pol
      alpha) inhibitors on a molecular level, a 3D homology model of the active site of
      the enzyme was proposed based on the application of molecular modelling methods
      and molecular dynamic simulations using available crystal coordinates of pol
      alpha relatives. Docking results for a series of known nucleotide analogue
      inhibitors were consistent with reported experimental binding data and offered
      the possibility to elucidate structure-activity relationships via investigations
      of active site-inhibitor interactions. Furthermore, the study could explain, at
      least partially, the inhibitory effect of aphidicolin on pol alpha. In molecular
      dynamics simulations, aphidicolin occupied the catalytic centre, but acted in a
      not truly competitive manner with respect to nucleotides. It destabilized the
      replicating "closed" form of the pol alpha and transferred the enzyme into the
      inactive "open" conformation. This result is consistent with recent experiments
      on the binding mode of aphidicolin.

PMID- 18341261
TI  - Carbonic anhydrase inhibitors. Inhibition of the cytosolic and tumor-associated
      carbonic anhydrase isozymes I, II and IX with some 1,3,4-oxadiazole- and 1,2,4
      triazole-thiols.
AB  - Novel mercapto-1,3,4-oxadiazole and -1,2,4-triazole derivatives were synthesized
      by various pathways starting from 4-(4-halogeno-phenylsulfonyl)benzoic acid
      hydrazides which were reacted with carbon disulfide or isothiocyanates. The
      heterocyclic mercaptans prepared in this way were assayed as inhibitors of three
      physiologically relevant isoforms of the zinc enzyme carbonic anhydrase (CA, EC
      4.2.1.1), i.e., the cytosolic CA I and II, and the tumor-associated,
      transmembrane isozyme CA IX. Interesting biological activity was detected for
      some of the new mercaptans, with inhibition constants in the low micromolar
      range.

PMID- 18341262
TI  - Synthesis, characterization and biological aspects of novel five-coordinated
      dimeric-Cu(II) systems.
AB  - The structural and spectroscopic properties of novel five-coordinated dimeric
      Cu(II) system have been investigated. The biocidal activities of all eight
      compounds, ligands, cupric nitrate and standard drugs against six bacteria and
      three fungi were determined. The DNA interaction activity of complexes was
      studied using spectrophotometry and electrophoresis. The superoxide dismutase
      (SOD)-like activity of the complexes was compared with previously reported
      monomeric- and dimeric copper complexes. The results support the five-coordinated
      dimeric square pyramidal geometry for the quinolone-Cu(II) system.

PMID- 18341263
TI  - Metal-based sulfonamides: their preparation, characterization and in-vitro
      antibacterial, antifungal & cytotoxic properties. X-ray structure of 4-[(2
      hydroxybenzylidene) amino] benzenesulfonamide.
AB  - Synthesis, characterization and biological studies of Schiff base-derived
      sulfonamides and their Co (II), Cu (II), Ni (II) and Zn (II) complexes have been
      reported and screened for in-vitro antibacterial activity against six Gram
      negative; E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis, S. typhi and S.
      dysenteriae and four Gram-positive; B. cereus, C. diphtheriae, S. aureus and S.
      pyogenes bacterial strains and for in-vitro antifungal activity against T.
      longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glaberata. All
      compounds showed moderate to significant antibacterial activity, however, the
      zinc (II) complexes were found to be more active. Some of the compounds also
      showed significant antifungal activity against various fungal strains. Only
      compounds (6) and (10) displayed potent cytotoxic activity with LD(50) = 4.644 x
      10(- 4) and 4.106 x 10(- 4) moles/mL respectively, against Artemia salina. The X
      ray structure of 4-[(2-hydroxybenzylidene)amino]benzenesulfonamide is also
      reported.

PMID- 18341264
TI  - A microtitre plate assay for measuring glycosidase activity.
AB  - Glycosidases perform a wide range of functions in physiology and pathology, and
      are potential targets for the treatment of diseases such as influenza, cancer,
      AIDS and diabetes. This paper reports a convenient discontinuous colourimetric
      assay for the measurement of glycosidase activity. The assay utilises 4
      nitrophenyl- substrates and quantities of product are determined by measuring
      absorbance at 405 nm. This assay is performed in a 96 well microtitre plate and
      has been used to characterise the properties of seven different glycosidases from
      bacteria, yeast and higher eukaryotes and their kinetic parameters determined.
      Assays in the presence of known inhibitors showed that inhibition modes can be
      determined, and IC(50) and K(i) values calculated. This assay appears to be of
      widely applicable and of general utility for the measurement of glycosidase
      activity and the evaluation of inhibitors.

PMID- 18341265
TI  - Antibacterial and antifungal activities of teucrium royleanum (Labiatea).
AB  - The crude methanolic extract and subsequent fractions of Teucrium royleanum
      (Labiatea) were screened for antibacterial and antifungal activities. Against
      tested pathogens, crude extract and subsequent fractions demonstrated moderate to
      excellent antibacterial activities. Highest antibacterial activity was displayed
      by the ethyl acetate fraction against S. typhi (100%), against E.coli (76.7%) and
      against P. aerugenosa (70.8%) followed by the chloroform fraction against S.
      typhi (85.7%). Similarly, the crude extract and its subsequent fractions showed
      mild to excellent activities in the antifungal bioassay with maximum antifungal
      activity against M. canis (87%) by the chloroform fraction followed by the ethyl
      acetate (71%) and n-butanol (70%) fractions.

PMID- 18341266
TI  - Lipoxygenase inhibiting and antioxidant iridoids from Buddleja crispa.
AB  - Phytochemical investigations on the ethyl acetate-soluble fraction of the whole
      plant of Buddleja crispa led to the isolation of the iridoids 1-7. Compound 2
      displayed significant inhibitory potential against enzyme lipoxygenase in a
      concentration-dependant fashion with IC(50) value of 39.7 +/- 0.02microM, along
      with DPPH radical scavenging activity with IC(50) value 0.638 mM.

PMID- 18341267
TI  - Effects of some antibiotics on human erythrocyte glutathione reductase: an in
      vitro study.
AB  - Inhibitory effects of some antibiotics on purified human erythrocyte glutathione
      reductase were investigated. Human erythrocyte glutathione reductase was purified
      2800-fold (29% yield) at 4 degrees C using 2', 5'-ADP Sepharose 4B affinity gel
      and Sephadex G-200 gel filtration chromatography. SDS polyacrylamide gel
      electrophoresis showed a single band for the enzyme. Imipenem, rifamycin,
      sulfanylacetamide, ceftazidime, chloramphenicol, seftriaxon, vancomycin,
      cefuroxime and ornidazole exhibited inhibitory effects but clindamycin,
      lincomycin, amoxicillin, amikacin exhibited activatory effects on the enzyme in
      vitro. The IC(50) values of imipenem, rifamycin, sulfanylacetamide, ceftazidime,
      chloramphenicol, seftriaxon, vancomycin, cefuroxime and ornidazole were 0.030,
      0.146, 0.59, 2.476, 2.36, 2.88, 4.83, 15.43 and 19.632 mM, respectively, and the
      K(i) constants were 0.06 +/- 0.01, 0.275 +/- 0.10, 0.85 +/- 0.05, 3.59 +/- 0.51,
      3.85 +/- 0.40, 3.71 +/- 0.60, 15.11 +/- 2.50, 23.50 +/- 2.94 and 28.49 +/- 6.50
      mM, respectively. While imipenem, rifamycin, sulfanylacetamide, ceftazidime,
      chloramphenicol and seftriaxon cefuroxime and ornidazole showed competitive
      inhibition, vankomycine displayed noncompetitive inhibition.

PMID- 18341268
TI  - In vitro prooxidant effect of caffeine.
AB  - Caffeine is a methylxanthine compound that acts as a stimulant in humans. It is
      the most widely consumed behaviourally active substance in the western world and
      it affects calcium influx and release in living cells. Caffeine is present in
      various substances such as tea, coffee and some medications. This article is
      focused on the impact of caffeine on oxidation. Caffeine promoted the
      peroxidation of linoleic acid emulsions used by 32.5, 48.9, and 54.3%,
      respectively, at 15, 30 and 45 microg/mL concentrations. Standard antioxidants
      such as alpha-tocopherol and trolox, a water-soluble analogue of tocopherol,
      inhibited 76.2 and 93.2% peroxidation of linoleic acid emulsion at 45 microg/mL
      concentration. Also, PC(50) value (caffeine concentration that produced a 50%
      increase in linoleic acid peroxidation) of caffeine was found to be 185 microM.

PMID- 18341269
TI  - Docking ligands into flexible and solvated macromolecules. 2. Development and
      application of fitted 1.5 to the virtual screening of potential HCV polymerase
      inhibitors.
AB  - HCV NS5B polymerase is a validated target for the treatment of hepatitis C, known
      to be one of the most challenging enzymes for docking programs. In order to
      improve the low accuracy of existing docking methods observed with this
      challenging enzyme, we have significantly modified and updated F itted 1.0, a
      recently reported docking program, into F itted 1.5. This enhanced version is now
      applicable to the virtual screening of compound libraries and includes new
      features such as filters and pharmacophore- or interaction-site-oriented docking.
      As a first validation, F itted 1.5 was applied to the testing set previously
      developed for F itted 1.0 and extended to include hepatitis C virus (HCV)
      polymerase inhibitors. This first validation showed an increased accuracy as well
      as an increase in speed. It also shows that the accuracy toward HCV polymerase is
      better than previously observed with other programs. Next, application of F itted
      1.5 to the virtual screening of the Maybridge library seeded with known HCV
      polymerase inhibitors revealed its ability to recover most of these actives in
      the top 5% of the hit list. As a third validation, further biological assays
      uncovered HCV polymerase inhibition for selected Maybridge compounds ranked in
      the top of the hit list.

PMID- 18341270
TI  - Glycoside esters of 5-aminolevulinic acid for photodynamic therapy of cancer.
AB  - Aliphatic and ethylene glycol esters of 5-aminolevulinic acid (ALA) are very
      efficient precursors of the photosensitizer protoporphyrin IX (PpIX) for
      photodynamic therapy; however, they diffuse passively across the cell membrane
      and thus lack cell selectivity. We evaluated whether alpha-glucose, alpha
      mannose, or beta-galactose esters of ALA would present improved properties as
      precursors of PpIX. Esterification was performed either at the position O-1 or O
      6 of the sugars with or without an ethylene glycol linker, and these glycoside
      esters of ALA were evaluated in human cells. The results demonstrated that
      glycoside esters of ALA are efficient precursors of PpIX in human cancer and
      angiogenic endothelial cells, comparable to free ALA, but not in normal human
      fibroblasts. PpIX production was confirmed by fluorescence microscopy and
      photodynamic treatment of cells. The O-1 or O-6 positions of functionalization
      and the nature of the sugar moiety did not influence PpIX production. The
      presence of the ethylene glycol linker generally resulted in decreased PpIX
      production. The uptake of these glycoside esters of ALA by cells was not
      decreased in the presence of high concentrations of the related sugars.
      Inhibitors of alpha-glucosidases or alpha-mannosidases did not decrease PpIX
      production. These results suggest the involvement of active non-glycoside
      specific membrane transporter(s) for uptake and of esterases rather than
      glycosidases in the release of ALA from the glycoside esters of ALA.

PMID- 18341271
TI  - Amphiphilic copolymer for delivery of xenobiotics: in vivo studies in a
      freshwater invertebrate, a Mesostominae flatworm.
AB  - The synthesis of an amphiphilic polymethacrylate copolymer containing cholesterol
      hydrophobic moieties and rhodamine as a fluorescent probe, the formation of
      microspheres, and the uptake of these microspheres in an invertebrate are
      reported. The cholesterol-derived methacryloyl monomer, which was prepared via a
      one-step synthesis, was copolymerized with methacrylic acid and methacryloxyethyl
      thiocarbamoyl rhodamine B in the presence of AIBN as initiator. The obtained dye
      labeled copolymer was characterized by (1)H NMR and UV-vis spectroscopy.
      Fluorescence and TEM microscopies studies show that this amphiphilic copolymer
      aggregates to give microspheres with diameters ranging from approximately 3 to 11
      microm. The in vivo study in a freshwater invertebrate, a Mesostominae flatworm
      (Rhabdocoela, Thyphloplanidae), indicates that the microspheres enter the cells
      by endocytosis. The data collected demonstrate that the rhodamine B covalently
      attached to the amphiphilic copolymers is bioaccumulated without being
      translocated out of the cell by the multixenobiotic resistance (MXR)
      transporters. As the MXR system is similar to the multidrug resistance (MDR)
      first observed in tumor cell lines resistant to anticancer drugs, the present
      data confirm the significant role that amphiphilic copolymers can play in the
      ongoing development of drug delivery strategies to overcome multidrug resistance.
      These investigations illustrate a promising approach for the development of new
      medical and ecotoxicological tools that can deliver specific molecules within
      cells.

PMID- 18341272
TI  - Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel
      [18F]fluorinated aldehyde-containing prosthetic groups.
AB  - Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for
      the (18)F-labeling of peptides for quantitative receptor imaging using positron
      emission tomography (PET). In this study, we extend the toolbox of oxime
      chemistry to include the novel prosthetic groups [(18)F]-(2-{2-[2-(2
      fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [(18)F]5, and [(18)F]-4-(3
      fluoropropoxy)benzaldehyde, [(18)F]9, in addition to the widely used 4
      [(18)F]fluorobenzaldehyde, [(18)F]12. The three (18)F-aldehydes were conjugated
      to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group
      on biodistribution and tumor uptake studied in mice. The peptide conjugate
      [(18)F]7 was found to possess superior in vivo pharmacokinetics with higher tumor
      to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either
      [(18)F]10 or [(18)F]13. The radioactivity from the [(18)F]7 conjugate excreted
      more extensively through the kidney route with 79%id passing through the urine
      and bladder at the 2 h time point compared to around 55%id for the more
      hydrophobic conjugates [(18)F]10 and [(18)F]13. The chemical nature of a
      prosthetic group can be employed to tailor the overall biodistribution profile of
      the radiotracer. In this example, the hydrophilic nature of the ethylene glycol
      containing prosthetic group [(18)F]5 clearly influences the overall excretion
      pattern for the RGD peptide conjugate.

PMID- 18341273
TI  - Novel prostaglandin D synthase inhibitors generated by fragment-based drug
      design.
AB  - We describe the discovery of novel inhibitors of prostaglandin D2 synthase (PGDS)
      through fragment-based lead generation and structure-based drug design. A library
      of 2500 low-molecular-weight compounds was screened using 2D nuclear magnetic
      resonance (NMR), leading to the identification of 24 primary hits. Structure
      determination of protein-ligand complexes with the hits enabled a hit
      optimization process, whereby we harvested increasingly more potent inhibitors
      out of our corporate compound collection. Two iterative cycles were carried out,
      comprising NMR screening, molecular modeling, X-ray crystallography, and in vitro
      biochemical testing. Six novel high-resolution PGDS complex structures were
      determined, and 300 hit analogues were tested. This rational drug design
      procedure culminated in the discovery of 24 compounds with an IC 50 below 1
      microM in the in vitro assay. The best inhibitor (IC 50 = 21 nM) is one of the
      most potent inhibitors of PGDS to date. As such, it may enable new functional in
      vivo studies of PGDS and the prostaglandin metabolism pathway.

PMID- 18341274
TI  - Two-step synthesis of achiral dispiro-1,2,4,5-tetraoxanes with outstanding
      antimalarial activity, low toxicity, and high-stability profiles.
AB  - A rapid, two-step synthesis of a range of dispiro-1,2,4,5-tetraoxanes with potent
      antimalarial activity both in vitro and in vivo has been achieved. These 1,2,4,5
      tetraoxanes have been proven to be superior to 1,2,4-trioxolanes in terms of
      stability and to be superior to trioxane analogues in terms of both stability and
      activity. Selected analogues have in vitro nanomolar antimalarial activity and
      good oral activity and are nontoxic in screens for both cytotoxicity and
      genotoxicity. The synthesis of a fluorescent 7-nitrobenza-2-oxa-1,3-diazole (NBD)
      tagged tetraoxane probe and use of laser scanning confocal microscopy techniques
      have shown that tagged molecules accumulate selectively only in parasite infected
      erythrocytes and that intraparasitic formation of adducts could be inhibited by
      co-incubation with the iron chelator desferrioxamine (DFO).

PMID- 18341275
TI  - On the mechanism of asymmetric allylation of aldehydes with allyltrichlorosilanes
      catalyzed by QUINOX, a chiral isoquinoline N-oxide.
AB  - Allylation of aromatic aldehydes 1a-m with allyl- and crotyl-trichlorosilanes 2-
      4, catalyzed by the chiral N-oxide QUINOX (9), has been found to exhibit a
      significant dependence on the electronics of the aldehyde, with p
      (trifluoromethyl)benzaldehyde 1g and its p-methoxy counterpart 1h affording the
      corresponding homoallylic alcohols 6g, h in 96 and 16% ee, respectively, at -40
      degrees C. The kinetic and computational data indicate that the reaction is
      likely to proceed via an associative pathway involving neutral, octahedral
      silicon complex 22 with only one molecule of the catalyst involved in the rate-
      and selectivity-determining step. The crotylation with (E) and (Z)
      crotyltrichlorosilanes 3 and 4 is highly diastereoselective, suggesting the
      chairlike transition state 5, which is supported by computational data. High
      level quantum chemical calculations further suggest that attractive aromatic
      interactions between the catalyst 9 and the aldehyde 1 contribute to the
      enantiodifferentiation and that the dramatic drop in enantioselectivity, observed
      with the electron-rich aldehyde 1h, originates from narrowing the energy gap
      between the (R)- and (S)-reaction channels in the associative mechanism (22).
      Overall, a good agreement between the theoretically predicted
      enantioselectivities for 1a and 1h and the experimental data allowed to
      understand the specific aspects of the reaction mechanism.

PMID- 18341276
TI  - Diiron dithiolato carbonyls related to the H(ox)CO state of [FeFe]-hydrogenase.
AB  - Oxidation of the electron-rich (E(1/2) = -175 vs Ag/AgCl) ethanedithiolato
      complex Fe2(S2C2H4)(CO)2(dppv)2 (1) under a CO atmosphere yielded [Fe2(S2C2H4)(mu
      CO)(CO)2(dppv)2](+) ([1(CO)](+)), a model for the H(ox)(CO) state of the [FeFe]
      hydrogenases. This complex exists as two isomers: a kinetically favored
      unsymmetrical derivative, unsym-[1(CO)](+), and a thermodynamically favored
      isomer, sym-[1(CO)](+), wherein both diphosphines span apical and basal sites.
      Crystallographic characterization of sym-[1(CO)](+) confirmed a C2-symmetric
      structure with a bridging CO ligand and an elongated Fe-Fe bond of 2.7012(14) A,
      as predicted previously. Oxidation of sym-[1(CO)](+) and unsym-[1(CO)](+) again
      by 1e(-) oxidation afforded the respective diamagnetic diferrous derivatives
      where the relative stabilities of the sym and unsym isomers are reversed. DFT
      calculations indicate that the stabilities of sym and unsym isomers are affected
      differently by the oxidation state of the diiron unit: the mutually trans CO
      ligands in the sym isomer are more destabilizing in the mixed-valence state than
      in the diferrous state. EPR analysis of mixed-valence complexes revealed that,
      for [1](+), the unpaired spin is localized on a single iron center, whereas for
      unsym/sym-[1(CO)](+), the unpaired spin was delocalized over both iron centers,
      as indicated by the magnitude of the hyperfine coupling to the phosphine ligands
      trans to the Fe-Fe vector. Oxidation of 1 by 2 equiv of acetylferrocenium
      afforded the dication [1](2+), which, on the basis of low-temperature IR
      spectrum, is structurally similar to [1](+). Treatment of [1](2+) with CO gives
      unsym-[1(CO)](2+).

PMID- 18341277
TI  - Modeling the catalysis of anti-cocaine catalytic antibody: competing reaction
      pathways and free energy barriers.
AB  - The competing reaction pathways and the corresponding free energy barriers for
      cocaine hydrolysis catalyzed by an anti-cocaine catalytic antibody, mAb15A10,
      were studied by using a novel computational strategy based on the binding free
      energy calculations on the antibody binding with cocaine and transition states.
      The calculated binding free energies were used to evaluate the free energy
      barrier shift from the cocaine hydrolysis in water to the antibody-catalyzed
      cocaine hydrolysis for each reaction pathway. The free energy barriers for the
      antibody-catalyzed cocaine hydrolysis were predicted to be the corresponding free
      energy barriers for the cocaine hydrolysis in water plus the calculated free
      energy barrier shifts. The calculated free energy barrier shift of -6.87 kcal/mol
      from the dominant reaction pathway of the cocaine benzoyl ester hydrolysis in
      water to the dominant reaction pathway of the antibody-catalyzed cocaine
      hydrolysis is in good agreement with the experimentally derived free energy
      barrier shift of -5.93 kcal/mol. The calculated mutation-caused shifts of the
      free energy barrier are also reasonably close to the available experimental
      activity data. The good agreement suggests that the protocol for calculating the
      free energy barrier shift from the cocaine hydrolysis in water to the antibody
      catalyzed cocaine hydrolysis may be used in future rational design of possible
      high-activity mutants of the antibody as anti-cocaine therapeutics. The general
      strategy of the free energy barrier shift calculation may also be valuable in
      studying a variety of chemical reactions catalyzed by other antibodies or
      proteins through noncovalent bonding interactions with the substrates.

PMID- 18341278
TI  - Photocurrent-generating properties of organometallic fullerene molecules on an
      electrode.
AB  - Compact, rigid, five-legged fullerene derivatives C60R5Me and M(C60R5)Cp (M = Fe
      and Ru; R = C6H4COOH, C6H4C6H4COOH, and CH2COOH) were synthesized and arrayed on
      an indium-tin oxide (ITO) surface. These devices exhibit a respectable quantum
      yield with photocurrent generation up to 18%, and, more importantly, the
      direction of the photocurrent can be changed not only by the molecular structure
      itself but also by changing the geometric configuration of the photoactive
      acceptor (fullerene) and donor (metal atom) on the ITO surface.

PMID- 18341279
TI  - Resolution enhancement in solid-state NMR of oriented membrane proteins by
      anisotropic differential linebroadening.
AB  - We demonstrate that a significant improvement in the spectral resolution may be
      achieved in solid-state NMR experiments of proteins in inhomogeneously disordered
      oriented lipid bilayers. Using 1H homonuclear decoupling instead of standard 1H
      heteronuclear decoupling, the 15N line widths may be reduced by up to seven times
      for such samples. For large oriented membrane proteins, such resolution
      enhancements may be crucial for assignment and structural interpretation.

PMID- 18341280
TI  - Coordination-driven self-assembly of cavity-cored multiple crown ether
      derivatives and poly[2]pseudorotaxanes.
AB  - The synthesis of a new 120 degree diplatinum(II) acceptor unit and the self
      assembly of a series of two-dimensional metallacyclic polypseudorotaxanes that
      utilize both metal-ligand and crown ether-dialkylammonium noncovalent
      interactions are described. Judiciously combining complementary diplatinum(II)
      acceptors with bispyridyl donor building blocks, with an acceptor and/or donor
      possessing a pendant dibenzo[24]crown-8 (DB24C8) moiety, allows for the formation
      of three new rhomboidal bis-DB24C8, one new hexagonal tris-DB24C8, and four new
      hexakis-DB24C8 metallacyclic polygons in quantitative yields. The size and shape
      of each assembly, as well as the location and stoichiometry of the DB24C8
      macrocycle, can be precisely controlled. Each polygon is able to complex two,
      three, or six dibenzylammonium ions without disrupting the underlying
      metallacyclic polygons, thus producing eight different poly[2]pseudorotaxanes and
      demonstrating the utility and scope of this orthogonal self-assembly technique.
      The assemblies are characterized with one-dimensional multinuclear ((1)H and
      (31)P) and two-dimensional ((1)H-(1)H COSY and NOESY) NMR spectroscopy as well as
      mass spectrometry (ESI-MS). Further analysis of the size and shape of each
      assembly is obtained through molecular force-field simulations. (1)H NMR
      titration experiments are used to establish thermodynamic binding constants and
      poly[2]pseudorotaxane/dibenzylammonium stoichiometries. Factors influencing the
      efficiency of poly[2]pseudorotaxane formation are discussed.

PMID- 18341281
TI  - Highly sensitive and stable humidity nanosensors based on LiCl doped TiO2
      electrospun nanofibers.
AB  - A new type of humidity nanosensor based on LiCl-doped TiO2 nanofibers with
      poly(vinyl pyrrolidone) (PVP) nanofibers as sacrificial template has been
      fabricated through electrospinning and calcination. The sensor exhibited
      excellent sensing characteristics, such as ultrafast response and recovery times,
      good reproducibility, linearity, and environmental stability, which are of
      importance for applications in humidity monitoring and control.

PMID- 18341282
TI  - Pentasaccharide glycosides from the tubers of sweet potato (Ipomoea batatas).
AB  - Sweet potato ( Ipomoea batatas) has been used as food and herb in many countries.
      In this research on the active constituents of sweet potato, nine compounds were
      isolated and identified, including seven new resin glycosides, batatosides A-G (1
      7), along with two known compounds, batatinoside I ( 8) and simonin IV ( 9). The
      structures of 1- 9 have been established by a combination of spectroscopic and
      chemical methods. The major characteristics of the new compounds are the presence
      of three different substituents. The absolute configuration of aglycones was
      established as S by Mosher's method. Batatoside E ( 5) showed weak cytotoxic
      activity against Hep-2 cells.

PMID- 18341283
TI  - Phase model interpretation of the structural properties of two molecular soy
      protein fractions.
AB  - The structural properties of mixtures of two molecular soy fractions, 11S
      (glycinin) and 2S, were investigated in the presence of glucono-delta-lactone
      (GDL) during an isothermal run at 25 degrees C for 1500 min. Analytical
      methodology included small-deformation dynamic oscillation, visual observations,
      scanning electron microscopy, and blending-law modeling. The aim of the work was
      to identify the state of phase separation and the pattern of solvent distribution
      between the two constituent polymers. It was found that the high molecular weight
      distribution of 11S supported rapid kinetics of structure formation, with this
      continuous matrix being concentrated and, hence, further reinforced in the
      presence of small additions of 2S. Blending-law modeling suggested that 2S was
      able to retain disproportionate volumes of solvent within its phase. A
      consequence of such property was that high additions of 2S leading to equal
      concentrations of the two molecular fractions in the blend resulted in a
      catastrophic drop in the values of the overall network strength. This behavior is
      rather unexpected for the structural properties of a phase-separated system, and
      it has been rationalized on the basis of the high water-holding capacity of the
      small molecular weight fraction. 2S entraps in its phase the polymeric segments
      of glycinin, which are then unable to become structural knots of a cohesive three
      dimensional morphology observed in single 11S preparations.

PMID- 18341284
TI  - Effect of sucrose on functional properties of soy globulins: adsorption and foam
      characteristics.
AB  - In this contribution, we have analyzed the effect of sucrose on dynamic
      interfacial (dynamic surface pressure and surface dilatational properties) and
      foaming (foam capacity and foam stability) characteristics of soy globulins (7S
      and 11S). The protein (at 1 x 10(-3), 1 x 10(-2), 0.1, and 1 wt %) and sucrose
      (at 0, 0.25, 0.5, and 1.0 M) concentrations in aqueous solution and the pH (at 5
      and 7), and ionic strength (at 0.05 and 0.5 M) were analyzed as variables. The
      temperature was maintained constant at 20 degrees C. We have observed the
      following. (i) The dynamics of adsorption (presence of a lag period, diffusion,
      and penetration at the air-water interface) of soy globulins depend on the
      peculiar molecular features of proteins (7S or 11S soy globulin) and the level of
      association/dissociation of these proteins by varying the pH and ionic strength,
      as well as the effect of sucrose in the aqueous phase on the unfolding of the
      protein. The rate of adsorption increases with the protein concentration in
      solution, at pH 7 compared to pH 5, at high ionic strength, and in the absence of
      sucrose. (ii) The surface dilatational properties reflect the fact that soy
      globulin adsorbed films exhibit viscoelastic behavior. The surface dilatational
      modulus increases at pH 7 compared to pH 5, but decreases with the addition of
      sucrose into the aqueous phase. (iii) The rate of adsorption and surface
      dilatational properties (surface dilatational modulus and phase angle) during
      adsorption at the air-water interface play an important role in the formation of
      foams generated from aqueous solutions of soy globulins. (iv) The increased
      interfacial adsorption (at high surface pressures) and the combined effects of
      interfacial adsorption and interfacial interactions between adsorbed soy globulin
      molecules (at high surface dilatational modulus) can explain the higher stability
      of the foam, with few exceptions.

PMID- 18341285
TI  - An efficient and facile synthesis of highly substituted 2,6-dicyanoanilines.
AB  - A one-pot procedure for the synthesis of substituted 2,6-dicyanoanilines starting
      from readily available ynones and malononitrile has been developed. For instance,
      penta-1,4-diyn-3-one is converted into the acetylene-substituted aniline
      derivative 1 in good yield. Upon photoexcitation, this chromophore shows a strong
      blue emission with a high quantum yield. The ground- and the excited-state
      geometries, charge distributions, and excitation energies of 1 have been
      evaluated by ab initio calculations.

PMID- 18341286
TI  - A potential route to neuroprostanes and isoprostanes: preparation of the four
      enantiomerically pure diastereomers of 13-F4t-neuroP.
AB  - We report a potential synthetic route to the isoprostanes and the neuroprostanes
      that could allow ready access to each of the enantiomerically pure diastereomers
      of the several regioisomers of these important human metabolites. The key
      transformation in the synthesis is a highly diastereoselective thermal
      intramolecular ene reaction. A critical observation is that the four
      enantiomerically pure diastereomers of an intermediate acetylenic ester are
      easily separated from one another. Each of these four has been carried on to a
      different enantiomerically pure diastereomer of 13-F4t-neuroprostane.

PMID- 18341287
TI  - Sesterterpenoids from the sponge Sarcotragus sp.
AB  - Nineteen new sesterterpenoids and eight known compounds were isolated from the
      sponge Sarcotragus sp. collected from Soheuksan Island, Korea. The structures of
      these compounds were determined to be linear sesterterpenoids containing furan or
      related oxygenated functionalities on the basis of combined chemical and
      spectroscopic analyses. In addition, the configurations of several previously
      undetermined compounds were assigned. Several compounds exhibited moderate to
      major antibacterial activity (compounds 1- 3, 17, 18) and cytotoxicity ( 3, 11,
      12) against the K562 cell line and inhibitory activity against isocitrate lyase (
      6, 13).

PMID- 18341288
TI  - alpha-Glucosidase inhibitory activity of triterpenoids from Cichorium intybus.
AB  - Two new triterpenoids, 18alpha,19beta-20(30)-taraxasten-3beta,21alpha-diol
      (cichoridiol) (1) and 17-epi-methyl-6-hydroxyangolensate (intybusoloid) (2), were
      obtained from the methanolic extract of seeds of Cichorium intybus along with 11
      known compounds, lupeol (3), friedelin (4), beta-sitosterol (5), stigmasterol
      (6), betulinic acid (7), betulin (8), betulinaldehyde (9), syringic acid (10),
      vanillic acid (11) 6,7-dihydroxycoumarin (12), and methyl-alpha-D
      galactopyranoside (13). Compounds 1, 1a, and 11 showed a good alpha-glucosidase
      inhibitory activity.

PMID- 18341289
TI  - Anionic phospholipids affect the rate and extent of flux through the
      mechanosensitive channel of large conductance MscL.
AB  - The mechanosensitive channel of large conductance MscL from Escherichia coli has
      been reconstituted into sealed vesicles, and the effects of lipid structure on
      the flux of the fluorescent molecule calcein through the open channel have been
      studied. The channel was opened by reaction of the G22C mutant of MscL with the
      reagent [2-(triethylammonium)ethyl]methanethiosulfonate (MTSET) which introduces
      five positive charges within the pore constriction. Flux through the channel was
      small when the lipid was phosphatidylcholine, but addition of the anionic lipids
      phosphatidylglycerol, phosphatidic acid, or cardiolipin up to 50 mol % resulted
      in increases in the amplitudes and rates of release of calcein. Similar effects
      were seen when either wild-type MscL or the G22C mutant was opened by osmotic
      pressure difference; rates of release of calcein were very slow in the absence of
      anionic lipid but increased with increasing concentrations of
      phosphatidylglycerol to 50 mol %. The observed partial release of trapped calcein
      following activation of MscL was attributed to the formation of a long-lived
      subconductance state of MscL following channel opening. Effects of anionic lipid
      were attributed to an increase in the rate of the transition from closed to fully
      open state and to a decrease in the rate of the transition from the fully open
      state to the subconductance state. Higher concentrations of anionic lipid led to
      a decrease in the rate and amplitude of release of calcein, possibly due to a
      decreased rate of flux through the open channel. In mixtures with anionic lipids,
      phosphatidylethanolamine resulted in lower rates and amplitude of release than
      phosphatidylcholine.

PMID- 18341290
TI  - Probing the acyl-binding pocket of aminoacylase-1.
AB  - The aminoacylase-1/metallopeptidase 20 (Acy1/M20) family features several l
      aminoacylases useful in biocatalysis. Mammalian Acy1, in particular, has been
      applied in racemic resolution and reverse hydrolysis. Despite recent advances in
      our understanding of the active site architecture and functioning, determinants
      of Acy1 substrate specificity have remained uncharted. Comparison to bacterial
      homologues points to a sterically more restricted acyl-binding pocket for Acy1.
      Here we sought to map characteristics of the acyl-binding pocket of human and
      porcine Acy1. Toward this end, we determined Michaelis constants for an analogue
      series of aliphatic N-acyl- l-methionine substrates and translated the values
      into three-dimensional quantitative structure-activity relationship models
      employing the minimal topological difference-partial least square method. The
      QSAR models for the two enzymes suggest overall similar binding pockets in the
      acetyl-binding portion and indicate a general preference for straight-chain acyl
      moieties. Embedding of the QSAR map for human Acy1 in the structure of its metal
      binding domain associates the side chain of Ile177 with limited acyl chain
      elongation which was not observed for the porcine enzyme. The topological model
      further supports roles of Thr347 and Leu372, which are both conserved in the
      porcine enzyme, in restricting acyl chain branching at the alpha- and beta
      positions, respectively. Mutational analyses confirmed our predictions for Thr347
      and Leu372. Moreover, the T347S variant of human Acy1 exhibited markedly
      increased catalytic efficiency against N-benzoylamino acids, demonstrating the
      potential for engineering of substrate specificity in Acy1. We discuss the more
      general application of the employed procedure for protein design.

PMID- 18341291
TI  - Characterization of Na,K-ATPase and H,K-ATPase enzymes with glycosylation
      deficient beta-subunit variants by voltage-clamp fluorometry in Xenopus oocytes.
AB  - The role of N-linked glycosylation of beta-subunits in the functional properties
      of the oligomeric P-type ATPases Na,K- and H,K-ATPase has been examined by
      expressing glycosylation-deficient Asn-to-Gln beta-variants in Xenopus oocytes.
      For both ATPases, the absence of the huge N-linked oligosaccharide moiety on the
      beta-subunit does not affect alpha/beta coassembly, plasma membrane delivery or
      functional activity of the holoenzyme. Whereas this is in line with several
      previous glycosylation studies on Na,K-ATPase, this is the first report showing
      that the cell surface delivery and enzymatic activity of the gastric H,K-ATPase
      is unaffected by the lack of N-linked glycosylation. Sulfhydryl-specific labeling
      of introduced cysteine reporter sites with the environmentally sensitive
      fluorophore tetramethylrhodamine-6-maleimide (TMRM) upon expression in Xenopus
      oocytes enabled us to further investigate potential effects of the N-glycans on
      more subtle enzymatic properties, like the distribution between E 1P/E 2P states
      of the catalytic cycle and the kinetics of the E 1P/E 2P conformational
      transition under presteady state conditions. For both Na,K-ATPase and H,K-ATPase,
      we observed differences in neither the voltage-dependent E 1P/E 2P ratio nor the
      kinetics of the E 1P/E 2P transition between holoenzymes comprising glycosylated
      and glycosylation-deficient beta-subunits. We conclude that the N-linked glycans
      on these essential accessory subunits of oligomeric P-type ATPases are
      dispensable for proper folding, membrane stabilization of the alpha-subunit and
      transport function itself. Glycosylation is rather important for other cellular
      functions not relevant in the oocyte expression system, such as intercellular
      interactions or basolateral versus apical targeting in polarized cells, as
      demonstrated in other expression systems.

PMID- 18341292
TI  - A single Caenorhabditis elegans Golgi apparatus-type transporter of UDP-glucose,
      UDP-galactose, UDP-N-acetylglucosamine, and UDP-N-acetylgalactosamine.
AB  - The genome of Caenorhabditis elegans encodes for 18 putative nucleotide sugar
      transporters even though its glycome only contains 7 different monosaccharides.
      To understand the biological significance of this phenomenon, we have begun a
      systematic substrate characterization of the above putative transporters and have
      determined that the gene ZK896.9 encodes a Golgi apparatus transporter for UDP
      glucose, UDP-galactose, UDP- N-acetylglucosamine, and UDP- N-acetylgalactosamine.
      This is the first tetrasubstrate nucleotide sugar transporter characterized for
      any organism and is also the first nonplant transporter for UDP-glucose. Evidence
      for the above substrate specificity and substrate transport saturation kinetics
      was obtained by expression of ZK896.9 in Saccharomyces cerevisiae followed by
      Golgi enriched vesicle isolation and assays in vitro. Further evidence for UDP
      glucose transport was obtained by expression of ZK 896.9 in Giardia lamblia, an
      organism recently characterized as having endogenous transport activity for only
      UDP- N-acetylglucosamine. Expression of ZK896.9 was also able to correct the
      phenotype of a mutant Chinese ovary cell line specifically defective in the
      transport of UDP-galactose into the Golgi apparatus and of a mutant of the yeast
      Kluyveromyces lactis specifically defective in the transport of UDP- N
      acetylglucosamine into its Golgi apparatus. Because up to now all three other
      characterized nucleotide sugar transporters of C. elegans have been found to
      transport two or three substrates, the substrate specificity of ZK896.9 raises
      questions as to the evolutionary ancestry of this group of proteins in this
      nematode.

PMID- 18341293
TI  - DNA tandem lesion repair by strand displacement synthesis and nucleotide excision
      repair.
AB  - DNA tandem lesions are comprised of two contiguously damaged nucleotides. This
      subset of clustered lesions is produced by a variety of oxidizing agents,
      including ionizing radiation. Clustered lesions can inhibit base excision repair
      (BER). We report the effects of tandem lesions composed of a thymine glycol and a
      5'-adjacent 2-deoxyribonolactone (LTg) or tetrahydrofuran abasic site (FTg). Some
      BER enzymes that act on the respective isolated lesions do not accept the tandem
      lesion as a substrate. For instance, endonuclease III (Nth) does not excise
      thymine glycol (Tg) when it is part of either tandem lesion. Similarly,
      endonuclease IV (Nfo) does not incise L or F when they are in tandem with Tg.
      Long-patch BER overcomes inhibition by the tandem lesion. DNA polymerase beta
      (Pol beta) carries out strand displacement synthesis, following APE1 incision of
      the abasic site. Pol beta activity is enhanced by flap endonuclease (FEN1), which
      cleaves the resulting flap. The tandem lesion is also incised by the bacterial
      nucleotide excision repair system UvrABC with almost the same efficiency as an
      isolated Tg. These data reveal two solutions that DNA repair systems can use to
      counteract the formation of tandem lesions.

PMID- 18341294
TI  - Crystal structure and mechanism of the Staphylococcus cohnii virginiamycin B
      lyase (Vgb).
AB  - The semisynthetic streptogramin antibiotic quinupristin/dalfopristin (trade name
      Synercid, Aventis Pharma) is a mixture of the A-type streptogramin dalfopristin
      and the B-type streptogramin quinupristin, a capped hexapeptide macrolactone.
      Quinupristin/dalfopristin was developed to combat multidrug resistant pathogens,
      but suffers from its own problems with drug resistance. Virginiamycin B lyase
      (Vgb) inactivates the quinupristin component of Synercid by lactone ring opening.
      Remarkably, the enzyme promotes this reaction by intramolecular beta-elimination
      without the involvement of a water molecule. Recently, structures of S. aureus
      Vgb in the presence and absence of substrate were reported and used together with
      detailed mutagenesis data to suggest a catalytic mechanism. Here, we report an
      independent determination of the S. cohnii Vgb crystal structure and a
      biochemical characterization of the enzyme. As expected, the S. cohnii and S.
      aureus Vgb structures and active sites are very similar. Moreover, both enzymes
      catalyze quinupristin lactone ring opening with similar rate constants, albeit
      perhaps with different dependencies on divalent metal ions. Replacement of the
      conserved active site residues His228, Glu268, or His270 with alanine reduces or
      abolishes S. cohnii Vgb activity. Residue Lys285 in S. cohnii Vgb is spatially
      equivalent to the S. aureus Vgb active site residue Glu284. A glutamate but not
      an alanine residue can substitute for the lysine without significant loss of
      activity.

PMID- 18341295
TI  - Interactions of the pleckstrin homology domain with phosphatidylinositol
      phosphate and membranes: characterization via molecular dynamics simulations.
AB  - The mechanism of interaction of pleckstrin homology (PH) domains with
      phosphatidylinositol 4,5-bisphosphate (PIP 2)-containing lipid bilayers remains
      uncertain. While crystallographic studies have emphasized PH-inositol 1,4,5
      trisphosphate (IP 3) interactions, biophysical studies indicate a degree of less
      specific protein-bilayer interactions. We have used molecular dynamics
      simulations to characterize the interactions of the PH domain from phospholipase
      C-delta1 with IP 3 and with PIP 2, the latter in lipid bilayers and in detergent
      micelles. Simulations of the PH domain in water reveal a reduction in protein
      flexibility when IP 3 is bound. Simulations of the PH domain bound to PIP 2 in
      lipid bilayers indicate a tightening of ligand-protein interactions relative to
      the PH-IP 3 complex, alongside formation of H-bonds between PH side chains and
      lipid (PC) headgroups, and a degree of penetration of hydrophobic side chains
      into the core of the bilayer. Comparison with simulations of the PH-bound domain
      to a PC bilayer in the absence of PIP 2 suggests that the presence of PIP 2
      increases the extent of PH-membrane interactions. Thus, comparative molecular
      dynamics simulations reveal how a PI-binding domain undergoes changes in
      conformational dynamics on binding to a PIP 2-containing membrane and how
      interactions additional to those with the PI headgroup are formed.

PMID- 18341296
TI  - Diversity-oriented fluorescence library approach (DOFLA) to the discovery of
      chymotrypsin sensor.
AB  - The diversity-oriented fluorescence library approach (DOFLA) has emerged and
      found applications in various fields to meet the acute demands for novel
      fluorescence sensors. The power of this approach has been demonstrated with the
      impressive discoveries of novel sensors for polymers such as DNA and heparin or
      for small molecules such as GTP and glutathione ( J. Am. Chem. Soc. 2003, 125,
      1130- 1131 ; J. Am. Chem. Soc. 2006, 128, 10380- 10381 ; J. Am. Chem. Soc. 2007,
      129, 4510- 4511 ; Chem. Commun. [Online early access]. DOI: 10.1039/b717058k.
      Published online Dec 11, 2008.
      http://www.rsc.org/publishing/journals/CC/article.asp?doi=b717058k ). Herein we
      report the application of this approach on quinaldinium fluorescent dye library
      synthesis on solid support and novel chymotrypsin sensor discovery. The new
      sensors are not only selective to chymotrypsin over other proteins but also only
      to the active conformation of chymotrypsin.

PMID- 18341297
TI  - Search for new red phosphors using genetic algorithm-assisted combinatorial
      chemistry.
AB  - A genetic algorithm was employed in association with high-throughput synthesis
      and characterization in an attempt to search for red phosphors with high
      photoluminescent intensity. A tetravalent manganese-doped alkali earth germanium
      oxide system, with an emission color close to a desirable deep red, was screened
      with the assistance of a genetic algorithm to pinpoint the phosphor exhibiting
      the highest photoluminescence. As the genetic algorithm was in progress, the PL
      intensity increased and maximized in the fourth generation. The highest and the
      average PL intensity of the fourth generation improved by 23 and 120%,
      respectively, compared with that of the first generation.

PMID- 18341298
TI  - Fabrication of very high aspect ratio metal nanowires by a self-propulsion
      mechanism.
AB  - A novel synthesis method of very high aspect ratio metal nanowires is described.
      The synthesis utilizes a nanoporous membrane as a template and self
      electrophoresis as a directed force that continuously push formed nanowires out
      of the pores in a rate that is identical to the rate of their elongation. As a
      result, while the pores of membranes are only 6 microm long, the formed nanowires
      could be more than 100 microm long.

PMID- 18341299
TI  - On the absence of detectable carrier multiplication in a transient absorption
      study of InAs/CdSe/ZnSe core/Shell1/Shell2 quantum dots.
AB  - Tunable femtosecond pump-near IR probe measurements on InAs/CdSe/ZnSe
      core/shell1/shell2 nanocrystal quantum dots were conducted to quantify
      spontaneous carrier multiplication previously reported in this system.
      Experimental conditions were chosen to eliminate the need for determining
      absolute wavelength dependent cross sections of the nanocrystals and allow direct
      comparison of band edge absorption bleach kinetics for different excitation
      energies up to 3.7 times the band gap. Results for two sample sizes show no signs
      of carrier multiplication within that range. This result is discussed in light of
      reports describing occurrence of this novel phenomenon in quantum dots based on
      this as well as numerous other semiconductor materials.

PMID- 18341300
TI  - Single-cell fluorescence imaging using metal plasmon-coupled probe 2: single
      molecule counting on lifetime image.
AB  - Multiple Alexa Fluor 647-conjugated concanavalin A (conA) molecules were
      covalently bound to a single 20 nm silver particle to synthesize metal plasmon
      coupled probes (PCPs). The fluorescence images were recorded by scanning confocal
      microscopy in both intensity and lifetime. The brightness of PCPs was 30-fold
      brighter than those of free conA and the lifetime of PCPs was shortened
      dramatically. PCPs were used to label T-lymphocytic ( PM1) cells. The emission
      spots by PCPs bound on the cell surfaces were separated clearly from the cell
      images by autofluorescence due to the brighter signal and shorter lifetime of
      PCPs. The emission spots by PCPs were also scanned in three dimensions to count
      the distribution of bound fluorophores on the cell surfaces. The metal-associated
      fluorophores thus are suggested using as novel molecular imaging agents to
      quantify the components and describe their distributions on the cell surfaces.

PMID- 18341301
TI  - Separation of single-walled carbon nanotubes by use of ionic liquid-aided
      capillary electrophoresis.
AB  - This paper presents a simple, highly efficient method for analyzing single-walled
      carbon nanotube (SWNT) bundles based on (1) ultrasound-assisted
      solubilization/dispersion of SWNTs in the ionic liquid 1-butyl-3
      methylimidazolium tetrafluoroborate, (2) encapsulation of the nanotubes in sodium
      dodecyl sulfate micelles, and (3) analysis by capillary electrophoresis. The
      process by which SWNTs disperse in the ionic liquid was studied by Raman
      spectroscopy. No degradation of SWNTs was observed under mild sonication
      conditions. The shape and position changes observed in the Raman spectral bands
      for the nanotubes are ascribed to debundling and interaction with the ionic
      liquid. Separation of solubilized SWNTs was accomplished by using a 50 mM formic
      acid solution at pH 2.0 as background electrolyte and a potential of -10 kV.
      Under these conditions, separation was completed within only 4 min. Eighteen
      peaks for SWNTs were identified in the analysis of commercial SWNT bundles. The
      two types of bundles studied exhibited distinct, highly characteristic
      electrophoretic profiles which could be used to control SWNTs purity.

PMID- 18341302
TI  - Microplate-compatible biamperometry array for parallel 48-channel amperometric or
      coulometric measurements.
AB  - We report a new reusable electrochemical array for parallel biamperometric
      measurements that has been designed for use with standard microplates. The 48
      channel array uses half of the available 96 wells and has 48 pairs of Pt wire
      electrodes. Applications to the quantitation of a variety of oxidizable species,
      including acetaminophen, ascorbic acid, hydroquinone, trolox, and uric acid, are
      demonstrated in assays that use potassium ferricyanide as an oxidant to produce a
      mixture of ferri- and ferrocyanide. Hydrogen peroxide quantitation is also
      demonstrated, based on an assay in which ferrocyanide is oxidized, again to
      produce a mixture of ferri- and ferrocyanide. Detection limits (signal-to-noise
      ratio (S/N) = 3) in these assays range from 1 (acetaminophen, R2 = 0.994) to 8
      microM (ascorbic acid, R2 = 0.967), and linearity was observed to analyte
      concentrations of at least 100 microM. We also demonstrate the application of the
      biamperometric array to enzymatic assays, using the glucose oxidase reaction as
      an example; following a 20 min enzyme reaction time, a detection limit of 0.1 mM
      glucose was obtained. These results indicate that applications to other oxidase
      based assays are feasible in this high-throughput format. The new electrochemical
      array employs standard, inexpensive microplates, and the biamperometric
      measurements are simple, precise, and rapid, requiring only 2 min for 48 parallel
      measurements.

PMID- 18341303
TI  - Intercomparison of infrared cavity leak-out spectroscopy and gas chromatography
      flame ionization for trace analysis of ethane.
AB  - Comparison of two different methods for the measurement of ethane at the parts
      per-billion (ppb) level is reported. We used cavity leak-out spectroscopy (CALOS)
      in the 3 microm wavelength region and gas chromatography-flame ionization
      detection (GC-FID) for the analysis of various gas samples containing ethane
      fractions in synthetic air. Intraday and interday reproducibilities were studied.
      Intercomparing the results of two series involving seven samples with ethane
      mixing ratios ranging from 0.5 to 100 ppb, we found a reasonable agreement
      between both methods. The scatter plot of GC-FID data versus CALOS data yields a
      linear regression slope of 1.07 +/- 0.03. Furthermore, some of the ethane
      mixtures were checked over the course of 1 year, which proved the long-term
      stability of the ethane mixing ratio. We conclude that CALOS shows equivalent
      ethane analysis precision compared to GC-FID, with the significant advantage of a
      much higher time resolution (<1 s) since there is no requirement for sample
      preconcentration. This opens new analytical possibilities, e.g., for real-time
      monitoring of ethane traces in exhaled human breath.

PMID- 18341304
TI  - Theoretical studies of the tautomers of pyridinethiones.
AB  - Pyridinethiones are important ligand precursors of coordination complexes of
      therapeutic value. In aqueous solution, pyridinethiones can dimerize and
      tautomerize to the corresponding thiols. However, the tautomerism of
      pyridinethiones, which can impact on therapeutic performance, is yet not fully
      understood. To resolve this important issue, we have carried out ab initio and
      DFT calculations to compute the geometries, energies, dipole moments, and NMR,
      IR, and UV-vis spectroscopic properties of all possible tautomers of
      pyridinethiones and compared our theoretical results with the existing
      experimental data. We found that the thione form of the tautomer is dominant for
      monomers of the pyridinethiones studied here. This work can serve as a reference
      for exploring other similar organosulfur compounds.

PMID- 18341305
TI  - Evidence of an unexpectedly long C-C bond (>2.7 A) in 1,3-metalladiyne complexes
      [Cp2MCCR]2 (M = Ti, Zr): QTAIM and ELF analyses.
AB  - Topological analyses of the electron density using the quantum theory of atoms in
      molecules (QTAIM) and electron localization function (ELF) have been carried out,
      at the B3LYP/DGVZVP and MP2/DGVZVP theoretical levels, on different 1,3
      metalladiyne cyclic compounds [Cp2M(CCR)]2, (M = Ti, Zr; R = F, CH3, H, SiH3).
      The QTAIM results indicate the presence of an extraordinarily long C-C bond (in a
      2.7-3.0 A range) connecting the CCR moieties, contrary to the common geometrical
      assumption of a M-M bond in similar metallacycles. The existence of this C-C bond
      is also supported by the distinct consequences on the reaction profiles for the
      Ti and Zr complexes, the CC oxidative coupling reactions being favored only for
      the Ti complexes. Moreover, the consequences of this bonding in the
      coupling/cleavage reactions of these metallacyclic complexes are reported and
      analyzed, revealing the transcendence of these long-range bonds in the overall
      behavior of these compounds.

PMID- 18341306
TI  - Competing channels in the thermal decomposition of azidoacetone studied by
      pyrolysis in combination with molecular beam mass spectrometric techniques.
AB  - The thermal decomposition of azidoacetone (CH3COCH2N3) was studied using a
      combined experimental and computational approach. Flash pyrolysis at a range of
      temperatures (296-1250 K) was used to induce thermal decomposition, and the
      resulting products were expanded into a molecular beam and subsequently analyzed
      using electron bombardment ionization coupled to a quadrupole mass spectrometer.
      The advantages of this technique are that the parent molecules spend a very short
      time in the pyrolysis zone (20-30 mus) and that the subsequent expansion permits
      the stabilization of thermal products that are not observable using conventional
      pyrolysis methods. A detailed analysis of the mass spectra as a function of
      pyrolysis temperature revealed the participation of five thermal decomposition
      channels. Ab initio calculations on the stable structures and transition states
      of the azidoacetone system in combination with an analysis of the dissociative
      ionization pattern of each channel allowed the identity and mechanism of each
      channel to be elucidated. At low temperatures (296-800 K) the azide decomposes
      principally by the loss of N2 to yield the imine (CH3COCHNH), which can further
      decompose to CH3CO and CHNH. At low and intermediate temperatures a process
      involving the loss of N2 to yield CH3CHO and HCN is also open. Finally, at high
      temperatures (800-1250 K) a channel in which the azide decomposes to a stable
      cyclic amine (CO(CH2)2NH) (after loss of N2) is active. The last channel involves
      subsequent thermal decomposition of this cyclic amine to ketene (H2CCO) and
      methanimine (H2CNH).

PMID- 18341307
TI  - Molecular self-assembly inhibition leads to basket-shaped cyclophane formation
      with chiral dynamics.
AB  - Planar perylene derivatives form macrocyclic dimers and concatenated dimer-dimer
      rings under the action of molecular self-assembly. If this underpinning principle
      is true, highly twisted perylene derivatives should be more frustrated toward
      formation of multimeric cyclic compounds such as macrocyclic dimers and
      concatenated dimer-dimers because of perturbation resulting from intermolecular
      pi-pi stacking. Indeed, 1,6,7,12- tetraphenoxy-substituted perylene is highly
      twisted and undergoes unimolecular cyclization rather than bimolecular or
      multimolecular cyclization. The resulting monocyclic monomer exhibits interesting
      conformation switching from one chiral structure (left-handedness) to another
      chiral structure (right-handedness) at room temperature. NMR studies of
      conformational dynamics reveal that such configuration change between the two
      enantiomers can be frozen at low temperature (-45 degrees C). An activation
      enthalpy barrier of 13.4 +/- 0.5 kcal.mol-1 for twisting the perylene plane in
      order to convert from one enantiomer to the other has been found.

PMID- 18341308
TI  - Proton-coupled hole transfer in X-irradiated doped crystalline cytosine.H2O.
AB  - Following exposure to X-irradiation at low temperatures, the main reactions
      taking place in single crystals of cytosine monohydrate doped with minute amounts
      of 2-thiocytosine are hole transfer (HT) from the electron-loss centers to the
      dopant and recombination of oxidation and reduction products, assumedly by
      electron transfer. A huge deuterium kinetic isotope effect (KIE; >102-103) at 100
      K, together with the kinetic curves obtained and density functional theory (DFT)
      calculations of equilibrium energy changes, indicates that these reactions
      proceed through a concerted proton-coupled electron/hole transfer where the
      proton transfer occurs between hydrogen-bonded cytosine molecules. The
      temperature dependence of these reaction rates between 10 and 150 K in normal and
      partially deuterated samples was investigated by monitoring the growth and decay
      of the various radical species over time using electron paramagnetic resonance
      (EPR) spectroscopy. By assuming a random distribution of the hole donors and
      acceptors in the crystals, the data are consistent with an exponential distance
      dependent rate, giving a distance decay constant (beta) around 1 A-1 for the HT,
      which indicates that a long-range single-step superexchange mechanism mediates
      the charge transfer. The reactions undergo a transition from a slow, weakly
      temperature-dependent rate to an Arrhenius-type rate at 40-50 K, presumably being
      activated by excitation of low-frequency intermolecular vibrations that couple to
      the process. Below this transition temperature, the transfer probability might be
      dominated by temperature-independent nuclear tunneling. A similar beta value in
      both temperature regions suggests that hopping is not activated.

PMID- 18341309
TI  - Structure of the phenylacetylene-water complex as revealed by infrared
      ultraviolet double resonance spectroscopy.
AB  - The structure of the phenylacetylene-water complex has been elucidated based on
      spectral shifts in electronic and vibrational transitions. Phenylacetylene forms
      a cyclic complex with water incorporating C-H...O and O-H...pi hydrogen bonds,
      which is different from both the benzene-water and acetylene-water complexes,
      even though phenylacetylene combines the features of both benzene and acetylene.
      Formation of such a complex can be rationalized on the basis of cooperativity
      between the two sets of hydrogen bonds.

PMID- 18341310
TI  - Microsolvation of glycine: a DFT study.
AB  - PBE1PBE/6-311+G(d,p) computations exploring the microsolvation of neutral and
      zwitterionic glycine are reported. A broad configuration search was performed to
      identify the lowest energy clusters of glycine with one to seven water molecules.
      The structures of the clusters are analyzed on the basis of the hydrogen-bonding
      network established between the water molecules and between water and glycine.
      Neutral glycine is favored when associated with zero to six water molecules, but
      with seven water molecules the two structures are isoenergetic.

PMID- 18341311
TI  - Low-temperature FTIR spectroscopic and theoretical study on an energetic
      nitroimine: dinitroammeline (DNAM).
AB  - This paper presents an overview of recent progress in spectroscopic studies of
      the energetic nitroimine 4,6-bis(nitroimino)-1,3,5-triazinan-2-one (DNAM), based
      on experimental and theoretical data. The following topics are considered:
      variable temperature FTIR spectroscopy (4000-400 cm(-1)) applied to the study of
      natural and isotopically substituted (deuterated) samples aiming to obtain a
      successful vibrational assignment of the spectra and to investigate H-bonding
      interactions; extensive theoretical work based on accurate quantum chemical
      calculations (ab initio MP2 and DFT/B3LYP; harmonic and anharmonic vibrational
      calculations) to model and help interpreting the experimental findings, as well
      as to provide fundamental data on this simple prototype nitroimine that can be
      used as a starting point to the study of more complex related compounds. This
      work allowed us to reveal detailed features of the IR spectrum of the title
      compound, presenting, for the first time, plausible assignments.

PMID- 18341312
TI  - Thermochemistry and gas-phase ion energetics of 2-hydroxy-4-methoxy-benzophenone
      (oxybenzone).
AB  - We have investigated the thermochemistry and ion energetics of the oxybenzone (2
      hydroxy-4-methoxy-benzophenone, C14H12O3, 1H) molecule. The following parameters
      have been determined for this species: gas-phase enthalpy for the of neutral
      molecule at 298.15K, (Delta(f)H0(m)(g) = -303.5 +/- 5.1 kJ x mol-1), the
      intrinsic (gas-phase) acidity (GA(1H) = 1402.1 +/- 8.4 kJ x mol-1), enthalpy of
      formation for the oxybenzone anion (Delta(f)H0(m)(1-,g) = -402.3 +/- 9.8 kJ x mol
      1). We also have obtained the enthalpy of formation of, 4-hydroxy-4'
      methoxybenzophenone (Delta(f)H0(m)(g) = -275.4 +/- 10 kJ x mol-1) and 3
      methoxyphenol anion (Delta(f)H0(m)(C7H7O2-,g) = -317.7 +/- 8.7 kJ x mol-1). A
      reliable experimental estimation of enthalpy related to intramolecular hydrogen
      bonding in oxybenzone has also been obtained (30.1 +/- 6.3 kJ x mol-1) and
      compared with our theoretical calculations at the B3LYP/6-311++G** level of
      theory, by means of an isodesmic reaction scheme. In addition, heat capacities,
      temperature, and enthalpy of fusion have been determined for this molecule by
      differential scanning calorimetry.

PMID- 18341313
TI  - Stereoelectronic effects on molecular geometries and state-energy splittings of
      ligated monocopper dioxygen complexes.
AB  - The relative energies of side-on versus end-on binding of molecular oxygen to a
      supported Cu(I) species, and the singlet versus triplet nature of the ground
      electronic state, are sensitive to the nature of the supporting ligands and, in
      particular, depend upon their geometric arrangement relative to the O2 binding
      site. Highly correlated ab initio and density functional theory electronic
      structure calculations demonstrate that optimal overlap (and oxidative charge
      transfer) occurs for the side-on geometry, and this is promoted by ligands that
      raise the energy, thereby enhancing resonance, of the filled Cu dxz orbital that
      hybridizes with the in-plane pi* orbital of O2. Conversely, ligands that raise
      the energy of the filled Cu dz2 orbital foster a preference for end-on binding as
      this is the only mode that permits good overlap with the in-plane O2 pi*. Because
      the overlap of Cu dz2 with O2 pi* is reduced as compared to the overlap of Cu dxz
      with the same O2 orbital, the resonance is also reduced, leading to generally
      more stable triplet states relative to singlets in the end-on geometry as
      compared to the side-on geometry, where singlet ground states become more easily
      accessible once ligands are stronger donors. Biradical Cu(II)-O2 superoxide
      character in the electronic structure of the supported complexes leads to
      significant challenges for accurate quantum chemical calculations that are best
      addressed by exploiting the spin-purified M06L local density functional, single
      reference completely renormalized coupled-cluster theory, or multireference
      second-order perturbation theory, all of which provide predictions that are
      qualitatively and quantitatively consistent with one another.

PMID- 18341314
TI  - Influence of ethanol on lipid membranes: from lateral pressure profiles to
      dynamics and partitioning.
AB  - We have combined experiments with atomic-scale molecular dynamics simulations to
      consider the influence of ethanol on a variety of lipid membrane properties. We
      first employed isothermal titration calorimetry together with the solvent-null
      method to study the partitioning of ethanol molecules into saturated and
      unsaturated membrane systems. The results show that ethanol partitioning is
      considerably more favorable in unsaturated bilayers, which are characterized by
      their more disordered nature compared to their saturated counterparts. Simulation
      studies at varying ethanol concentrations propose that the partitioning of
      ethanol depends on its concentration, implying that the partitioning is a
      nonideal process. To gain further insight into the permeation of alcohols and
      their influence on lipid dynamics, we also employed molecular dynamics
      simulations to quantify kinetic events associated with the permeation of alcohols
      across a membrane, and to characterize the rotational and lateral diffusion of
      lipids and alcohols in these systems. The simulation results are in agreement
      with available experimental data and further show that alcohols have a small but
      non-vanishing effect on the dynamics of lipids in a membrane. The influence of
      ethanol on the lateral pressure profile of a lipid bilayer is found to be
      prominent: ethanol reduces the tension at the membrane-water interface and
      reduces the peaks in the lateral pressure profile close to the membrane-water
      interface. The changes in the lateral pressure profile are several hundred
      atmospheres. This supports the hypothesis that anesthetics may act by changing
      the lateral pressure profile exerted on proteins embedded in membranes.

PMID- 18341315
TI  - Pt(II) uptake by dendrimer outer pockets: 1. Solventless ligand exchange
      reaction.
AB  - Density functional theory is used to elucidate molecular-level details of the
      complexation of Pt(II) metal compounds with PAMAM dendrimers. Particular
      attention is given to the ligand exchange reaction (LER). Binding of Pt(II)
      complexes to one dendrimer atom site (monodentate binding) is found to be
      thermodynamically feasible. Tertiary amine nitrogen (N3) is found to be the most
      favorable binding site in agreement with previous experimental work. Comparing
      the binding of Pt(II) species to atom sites in simple molecules with those to
      similar sites in dendrimer outer pockets allowed us to assess the impact of
      dendrimer branches on the binding. The impact of branches is manifested in more
      complex reaction profiles for complexation of Pt(II) species, because of the
      numerous ways in which a single molecule could be hosted by an outer dendrimer
      pocket. It is found that branches slightly improve the binding strength to all
      sites, particularly to N3. However, they could also be responsible for the
      increase of the activation energy for direct LER of PtCl(4)(2-) and
      PtCl(3)(H(2)O)- at the N3 site. Considering the thermodynamics of both
      complexation steps, namely noncovalent binding (NCB) and LER, it is found that to
      have a PtCl(3)(-) moiety bound to N3, as a result of NCB + LER operating on
      PtCl(4)(2-), is more likely than to have any other ion hosted in the outer
      pockets. However, the activation energy for direct LER of PtCl(4)(2-) at the N3
      site is found to be the largest among all Pt(II) metal complexes and even larger
      than the barrier to its own aquation yielding PtCl(3)(H(2)O)(-).

PMID- 18341316
TI  - Pt(II) uptake by dendrimer outer pockets: 2. Solvent-mediated complexation.
AB  - We study the effect of the solvent (water) on the ligand exchange reaction (LER)
      step of Pt(II) complexation to PAMAM dendrimers. The results suggest that
      aquation of tetrachloroplatinate anion (PtCl(4)(2-)) inside PAMAM outer pockets
      occurs prior to its reaction with dendrimer atom binding sites. Thus, the active
      involvement of water opens up several pathways by which Pt(II) can bind to
      tertiary amine sites (N3). Monodentate binding pathways by which a PtCl(3)(-)
      moiety is obtained as a final product rather than PtCl(2)(H(2)O) are considered
      to be the predominant routes due to their smaller degree of complexity, including
      aspects such as less number of intermediates and lower energy barriers.
      Monodentate binding of Pt(II) to the secondary amide site (N2) is found to be
      feasible, in agreement with previous NMR experiments, once aquation of the
      tetrachloroplatinate anion has occurred. For this type of binding to occur, the
      dendrimer branch amide group configuration would have to switch from its
      equilibrium position (trans) to a cis position. It is also found that outer
      pockets aid Pt(II) complexation with the dendrimer mainly by making the
      noncovalent binding (NCB) step more favorable than that in branchless
      environments. Finally, our results predict that competitive monodentate binding
      of Pt(II) to either N3 or N2 is thermodynamically rather than kinetically driven.

PMID- 18341317
TI  - Release of lysozyme from the branched polyelectrolyte-lysozyme complexation.
AB  - On the basis of the discretely charged sphere model of lysozyme, the release
      behavior of lysozyme from the branched polyelectrolyte-lysozyme complexation is
      investigated by adding salt and changing the pH values of the solution. It is
      found that, with the increase of the salt ionic strength of the solution, the
      lysozymes are gradually released from the oppositely charged polyelectrolyte as a
      result of the screening of electrostatic attraction between the two ionic species
      by adding the salt. Interestingly, there exists a critical salt ionic strength at
      which all proteins are released from the branched polyelectrolyte, and the
      polyelectrolyte-protein complexation is broken completely. Beyond the critical
      value, the increase of the salt ionic strength causes self-association of the
      proteins released from the branched polyelectrolyte-protein complexation. The
      self-association of the protein is detrimental in biological systems. By
      calculating the second virial coefficient, we found that the optimal salt content
      for the dispersion of proteins coincides with the critical ionic strength,
      because the second virial coefficient reaches its maximum at the critical ionic
      strength. Similarly, increasing the pH value of the solution can also release the
      lysozymes from the polyelectrolyte, because the increase of pH value of the
      solution changes the charge distribution and net charge of the lysozyme, weakens
      the attraction between lysozymes mediated by polyelectrolyte, and finally leads
      to the dissolution of the complexation of branched polyelectrolyte with lysozymes
      in strong alkaline solution. In addition, by exploring the effect of architecture
      of the polyelectrolyte on the release behavior of proteins, we found that it is
      more difficult to release proteins from the branched polyelectrolyte than from
      the linear polyelectrolyte.

PMID- 18341318
TI  - Molecular mechanisms of cryoprotection in aqueous proline: light scattering and
      molecular dynamics simulations.
AB  - Free proline amino acid is a natural cryoprotectant expressed by numerous
      organisms under low-temperature stress. Previous reports have suggested that
      complex assemblies underlie its functional properties. We investigate here
      aqueous proline solutions as a function of temperature using combinations of
      Raman spectroscopy, Rayleigh-Brillouin light scattering, and molecular dynamics
      simulations with the view to revealing the molecular origins of the mixtures'
      functionality as a cryoprotectant. The evolution of the Brillouin frequency
      shifts and line widths with temperature shows that, above a critical proline
      concentration, the water-like dynamics is suppressed and viscoelastic behavior
      emerges: Here, the Landau-Placzek ratio also shows a temperature-independent
      maximum arising from concentration fluctuations. Molecular dynamics simulations
      reveal that the water-water correlations in the mixtures depend much more weakly
      on temperature than does bulk water. By contrast, the water OH Raman bands
      exhibit strong red-shifts on cooling similar to those seen in ices; however, no
      evidence of ice lattice phonons is observed in the low-frequency spectrum. We
      attribute this primarily to enhanced proline-water hydrogen bonding. In general,
      the picture that emerges is that aqueous proline is a heterogeneous mixture on
      molecular length scales (characterized by significant concentration fluctuations
      rather than well-defined aggregates). Simulations reveal that proline also
      appears to suppress the normal dependence of water structure on temperature and
      preserves the ambient-temperature correlations even in very cold solutions. The
      water structure in cold proline solutions therefore appears to be similar to that
      at a higher effective temperature. This, coupled with the emergence of glassy
      dynamics offers a molecular explanation for the functional properties of proline
      as a cryoprotectant without the need to invoke previously proposed complex
      aggregates.

PMID- 18341319
TI  - Complex of calcium receptor blocker nifedipine with glycyrrhizic acid.
AB  - Physicochemical methods were used to explore the regularities of complexing
      between the calcium channel blocker nifedipine (NF) and pharmaceutically
      acceptable complex-forming glycyrrhizic acid (GA) in view of the discovered
      influence of GA on the therapeutic activity of NF. 1H NMR (including relaxation
      measurements) and UV-vis spectra have produced illustrative evidence that NF
      forms stable complexes with GA within a wide concentration range, from 0.05 to 5
      mM. At low GA concentrations, below 0.5 mM, NF forms an inclusion complex where
      each NF molecule is bound by two molecules of GA. Computer simulations of the NMR
      experimental data have shown that, in aqueous solution, the stability constant of
      this complex, K, is about 10(5) M(-1). At higher concentrations, GA forms large
      micelle-like aggregates which increase the water solubility of NF. Quenching of
      chemically induced dynamic nuclear polarization effects in the photoinduced
      interaction of the NF-GA complex with tyrosine suggests that complex formation
      with GA completely blocks the single electron-transfer step between NF and the
      amino acid. This, arguably, could explain the increased therapeutic activity of
      GA complexes, since GA might protect the drug molecule from the reaction with
      amino acid residues of the receptor binding site.

PMID- 18341320
TI  - Structural organization in aqueous solutions of 1-Butyl-3-methylimidazolium
      halides: a high-pressure infrared spectroscopic study on ionic liquids.
AB  - High-pressure infrared spectroscopy was applied to study the hydrogen-bonding
      structures of 1-butyl-3-methylimidazolium halides/D2O mixtures. No drastic
      changes were observed in the concentration dependence of the alkyl C-H band
      frequency at high concentration of 1-butyl-3-methylimidazolium chloride.
      Nevertheless, the alkyl C-H exhibits an increase in frequency upon dilution at
      low concentration. These observations may indicate a clustering of the alkyl
      groups at high concentration and the formation of a certain water structure
      around alkyl C-H groups in the water-rich region. The imidazolium C-H band at ca.
      3051 cm(-1) displays a monotonic blue-shift in frequency as the sample was
      diluted at high concentration of 1-butyl-3-methylimidazolium chloride. That is,
      water can be added to change the structural organization of 1-butyl-3
      methylimidazolium chloride in the ionic liquid-rich composition region by
      introducing water-imidazolium C-H interactions. Analyzing the pressure dependence
      of the imidazolium C-H stretches yielded anomalous nonmonotonic pressure-induced
      frequency shifts. This result may reflect the strengthening of C-H-O interactions
      between imidazolium C-H groups and the water clusters. Density functional theory
      calculations also revealed that the characteristic bonded C2-H vibration may be
      shifted via the modification of C2-H-Cl- associations.

PMID- 18341321
TI  - Glassy protein dynamics and gigantic solvent reorganization energy of
      plastocyanin.
AB  - We report the results of molecular dynamics simulations of electron-transfer
      activation parameters of plastocyanin metalloprotein involved as an electron
      carrier in natural photosynthesis. We have discovered that slow, non-ergodic
      conformational fluctuations of the protein, coupled to hydrating water, result in
      a very broad distribution of donor-acceptor energy gaps far exceeding those
      observed for commonly studied inorganic and organic donor-acceptor complexes. The
      Stokes shift is not affected by these fluctuations and can be calculated from
      solvation models in terms of the linear response of the solvent dipolar
      polarization. The non-ergodic character of large-amplitude protein/water mobility
      breaks the strong link between the Stokes shift and the reorganization energy
      characteristic of equilibrium (ergodic) theories of electron transfer. This
      mechanism might be responsible for fast electronic transitions in natural
      electron-transfer proteins characterized by low reaction free energy.

PMID- 18341322
TI  - The thermal stability of lattice-energy minima of 5-fluorouracil: metadynamics as
      an aid to polymorph prediction.
AB  - This paper reports a novel methodology for the free-energy minimization of
      crystal structures exhibiting strong, anisotropic interactions due to hydrogen
      bonding. The geometry of the thermally expanded cell was calculated by exploiting
      the dependence of the free-energy derivatives with respect to cell lengths and
      angles on the average pressure tensor computed in short molecular dynamics
      simulations. All dynamic simulations were performed with an elaborate anisotropic
      potential based on a distributed multipole analysis of the isolated molecule
      charge density. Changes in structure were monitored via simulated X-ray
      diffraction patterns. The methodology was used to minimize the free energy at
      ambient conditions of a set of experimental and hypothetical 5-fluorouracil
      crystal structures, generated in a search for lattice-energy minima with the same
      model potential. Our results demonstrate that the majority ( approximately 75%)
      of lattice-energy minima are thermally stable at ambient conditions, and hence,
      the free-energy (like the lattice-energy) surface is complex and highly
      undulating. Metadynamics trajectories (Laio, A.; Parrinello, M. Proc. Natl. Acad.
      Sci. U.S.A. 2002, 99, 12562) started from the free-energy minima only produced
      transitions that preserved the hydrogen-bonding motif, and thus, further
      developments are needed for this method to efficiently explore such free-energy
      surfaces. The existence of so many free-energy minima, with large barriers for
      the alteration of the hydrogen-bonding motif, is consistent with the range of
      motifs observed in crystal structures of 5-fluorouracil and other 5-substituted
      uracils.

PMID- 18341323
TI  - Pulse radiolysis studies on reactions of hydroxyl radicals with selenocystine
      derivatives.
AB  - Reactions of hydroxyl radicals (*OH) with selenocystine (SeCys) and two of its
      analogues, diselenodipropionic acid (SeP) and selenocystamine (SeA), have been
      studied in aqueous solutions at pHs of 1, 7, and 10 using the pulse radiolysis
      technique coupled with absorption detection. All of these diselenides react with
      *OH radicals with rate constants of approximately 10(10) M(-1) s(-1), producing
      diselenide radical cations ( approximately 1-5 micros after the pulse), with an
      absorption maximum at 560 nm, by elimination of H(2)O or OH(-) from hydroxyl
      radical adducts. Assignment of the 560 nm band to the diselenide radical cation
      was made by comparing the transient spectra with those produced upon reaction of
      diselenides with specific one-electron oxidants, Cl(2)(*-) (pH 1) and Br(2)(*-)
      radicals (pHs of 7 and 10). SeP having a carboxylic acid functionality showed
      quantitative conversion of hydroxyl radical adducts to radical cations. The
      compounds SeCys and SeA, having an amino functional group, in addition to the
      radical cations, produced a new transient with lambda(max) at 460 nm, at later
      time scales ( approximately 20-40 micros after the pulse). The rate and yield of
      formation of the 460 nm band increased with increasing concentrations of either
      SeCys or SeA. In analogy with similar studies reported for analogous disulfides,
      the 460 nm transient absorption band has been assigned to a triselenide radical
      adduct. The one-electron reduction potentials of the compounds were estimated to
      be 0.96, 1.3, and 1.6 V versus NHE, respectively, for SeP, SeCys, and SeA at pH
      7. From these studies, it has been concluded that the electron-donating
      carboxylic acid group decreases the reduction potential and facilitates
      quantitative conversion of hydroxyl radical adducts to radical cations, while the
      electron-withdrawing NH(3)(+) group not only increases the reduction potential
      but also leads to fragmentation of the hydroxyl radical adduct to selenyl
      radicals, which are converted to triselenide radical adducts.

PMID- 18341324
TI  - Density measurement of 1-d confined water by small angle neutron scattering
      method: pore size and hydration level dependences.
AB  - Small angle neutron scattering (SANS) is used to measure the absolute density of
      water contained in 1-D cylindrical pores of a silica material MCM-41-S with pore
      diameters of 19 and 15 A. By being able to suppress the homogeneous nucleation
      process inside the narrow pore, one can keep water in the liquid state down to at
      least 160 K. From a combined analysis of SANS data from both H(2)O and D(2)O
      hydrated samples, we determined the absolute value of the density of 1-D confined
      water. We found that the average density of water inside the fully hydrated 19 A
      pore is 8% higher than that of the bulk water at room temperature. The
      temperature derivative of the density shows a pronounced peak at T(L) = 235 K
      signaling the crossing of the Widom line at ambient pressure and confirming the
      existence of a liquid-liquid phase transition at an elevated pressure. Pore size
      and hydration level dependences of the density are also studied.

PMID- 18341325
TI  - Self-assembly of the beta2-microglobulin NHVTLSQ peptide using a coarse-grained
      protein model reveals a beta-barrel species.
AB  - Although a wide variety of proteins can assemble into amyloid fibrils, the
      structure of the early oligomeric species on the aggregation pathways remains
      unknown at an atomic level of detail. In this paper we report, using molecular
      dynamics simulations with the OPEP coarse-grained force field, the free energy
      landscape of a tetramer and a heptamer of the beta2-microglobulin NHVTLSQ
      peptide. On the basis of a total of more than 17 ns trajectories started from
      various states, we find that both species are in equilibrium between amorphous
      and well-ordered aggregates with cross-beta-structure, a perpendicular bilayer
      beta-sheet, and, for the heptamer, six- or seven-stranded closed and open beta
      barrels. Moreover, analysis of the heptamer trajectories shows that the
      perpendicular bilayer beta-sheet is one possible precursor of the beta-barrel,
      but that this barrel can also be formed from a twisted monolayer beta-sheet with
      successive addition of chains. Comparison with previous aggregation simulations
      and the fact that nature constructs transmembrane beta-sheet proteins with pores
      open the possibility that beta-barrels with small inner diameters may represent a
      common intermediate during the early steps of aggregation.

PMID- 18341326
TI  - Quantum chemistry in solution by combining 3D integral equation theory with a
      cluster embedding approach.
AB  - Free energy changes associated with chemical reactions in solution are treated by
      integral equation theory in the form of the 3D reference interaction site model
      (RISM) in combination with quantum-chemical calculations via an embedded cluster
      approach (EC-RISM). The electronic structure of the solute is computed self
      consistently with the solvent structure by mapping the charge distribution of the
      solvent onto a set of discrete background point charges that are added to the
      molecular Hamiltonian. The EC-RISM procedure yields chemical accuracy in free
      energy predictions for several benchmark systems without adjusting empirical
      parameters. We apply the method to the standard reaction free energy for the
      gauche-trans equilibrium of 1,2-dichloroethane in water and to pKa shift
      calculations for trifluoroacetic acid/acetic acid and 4-nitroaniline/aniline in
      water.

PMID- 18341327
TI  - Physicochemical properties, structure, and conformations of 1-Butyl-3
      methylimidazolium bis(trifluoromethanesulfonyl)imide [C4mim]NTf2 ionic liquid.
AB  - Thermodynamic properties of 1-butyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide ([C4mim]NTf2) ionic liquid have been studied
      by adiabatic calorimetry in the temperature range of 5 to 370 K. This compound
      has been found to form crystal, liquid, and glass. The temperature and enthalpy
      of fusion for [C(4)mim]NTf(2) have been determined to be T(fus) = 270.22 +/- 0.02
      K and Delta(fus)H = 23.78 +/- 0.04 kJ.mol(-1), respectively. The heat capacity of
      crystalline [C(4)mim]NTf(2) in the T range of 205 to 255 K may vary by a few
      percent, subject to the procedure of the crystal preparation. The glass
      transition temperature for [C(4)mim]NTf(2) has been found to be T(g) = 181.5 +/-
      0.1 K. On the basis of the results of DFT quantum chemical calculations, the
      experimental vibrational spectra, and the available literature data,
      thermodynamic properties of [C(4)mim]NTf(2) in the ideal-gas state have been
      calculated by the statistical thermodynamic methods. The entropy values for the
      gaseous compound obtained from the experimental data and the calculations are in
      satisfactory agreement.

PMID- 18341328
TI  - Molecular basis of carbon dioxide transport in polycarbonate membranes.
AB  - Gas transport of carbon dioxide in poly[bisphenol A carbonate-co-4,4'-(3,3,5
      trimethylcyclohexylidene)diphenol carbonate] films over a wide range of pressure
      is described. The interpretation of the experimental results in terms of the dual
      mode model allowed the evaluation of the parameters of the model that govern the
      gas permeation process. The value of the diffusion coefficient obtained for
      carbon dioxide at zero concentration was 2.4 x 10(-8) cm(2) s(-1), at 303 K. This
      parameter was also measured by using pulsed field gradient NMR finding that its
      value reaches a nearly constant value of (2.7 +/- 0.9) x 10(-8) cm(2) s(-1), at
      298 K, for diffusion times greater than 20 ms. Both the diffusion and solubility
      coefficients were also computed by using simulation methods based on the
      transition states theory and the Widom method, respectively. The value obtained
      for the diffusion coefficient was 1.8 x 10(-8) cm(2) s(-1), at 303 K, which
      compares very favorably with the experimental measurements. The drop of the
      simulated solubility coefficient with increasing pressure is sharper than that of
      the experimental one, at low pressures, and similar, at high pressures.

PMID- 18341329
TI  - Effects of sugars and polyols on the stability of azurin in ice.
AB  - This study represents the first attempt to gain a quantitative estimate of the
      protective influence of sugars (sucrose and trehalose) and polyols (sorbitol and
      glycerol) on the thermodynamic stability (DeltaG degrees ) of a protein in low
      temperature part-frozen aqueous solutions. The method, based on guanidinium
      chloride denaturation of the azurin mutant C112S from Pseudomonas aeruginosa,
      distinguishes between the effects of cooling to subfreezing temperatures from
      those induced specifically by the formation of a solid ice phase. The results
      point out that in the liquid state the generally stabilizing effect (at molar
      concentrations) of these polyhydric compounds is markedly attenuated on cooling
      to subfreezing temperatures such that at -15 degrees C, only sucrose still exerts
      a significant increase in DeltaG degrees . At this temperature, and in the
      absence of additives, the formation of ice caused a progressive destabilization
      of the native fold, DeltaG degrees decreasing up to 3-4 kcal/mol as the fraction
      of liquid water in equilibrium with ice (V(L) was reduced to less than 1%.
      Unexpectedly, denaturation profiles in ice at selected V(L) demonstrate that none
      of the above sugars and polyols counters effectively the decrease in protein
      stability at small V(L). Only trehalose was able to partly attenuate the ice
      perturbation, raising DeltaG degrees by a modest 0.6-0.8 kcal/mol relative to the
      salt reference. In all cases the reduction in DeltaG degrees caused by the
      solidification of water correlates with the decrease in m-value. The implication
      is that DeltaASA of unfolding is smaller in ice because protein-ice interactions
      either increase the solvent-accessible surface area (ASA) of the native fold
      (partial unfolding) or reduce the ASA of the denatured state (compaction), or
      both. Information on the protein tertiary structure in ice, in the absence and in
      the presence of sucrose or glycerol, suggests that these osmolytes play an
      important role in maintaining a compact native state that in their absence is
      expanded and partly unfolded. Thus, it appears that the prevailing mechanism by
      which these osmolytes act as cryoprotectants is through preservation of the
      native conformation in the liquidus rather than by increasing the thermodynamic
      stability of the native fold.

PMID- 18341330
TI  - Colloidal shape controlled by molecular adsorption at liquid crystal interfaces.
AB  - The ability to control finely the structure of materials remains a central issue
      in colloidal science. Due to their elastic properties, liquid crystals (LC) are
      increasingly used to organize matter at the micrometer scale in soft composites.
      Textures and shapes of LC droplets are currently controlled by the competition
      between elasticity and anchoring, hydrodynamic flows, or external fields.
      Molecules adsorbed specifically at LC interfaces are known to orient LC molecules
      (anchoring effect), but other induced effects have been poorly explored. Using
      specifically designed amphitropic surfactants, we demonstrate that large-shape
      transformations can be achieved in direct LC/water emulsions. In particular, we
      focus on unusual nematic filaments formed from spherical droplets. These results
      suggest new approaches to design new soft LC composite materials through the
      adsorption of molecules at liquid crystal interfaces.

PMID- 18341331
TI  - The smallest amphiphiles: nanostructure in protic room-temperature ionic liquids
      with short alkyl groups.
AB  - Room-temperature ionic liquids (ILs) are low-melting-point organic salts that,
      until recently, were thought to have homogeneous microstructure. In this work, we
      investigate nanoscale segregation of short (<C(4)) alkyl chain ILs using
      propylammonium nitrate (PAN) and ethylammonium nitrate (EAN). Structure peaks at
      q = 0.54 A(-1) for PAN and at q = 0.66 A(-1) for EAN, corresponding to Bragg
      spacings (D* = 2pi/q(max)) of 11.6 and 9.7 A respectively, provide the first
      experimental evidence of nanoscale heterogeneity for ILs with alkyl chains less
      than C(4). The observation that these ILs are not optically birefringent and the
      fits obtained suggest a disordered, locally smectic or sponge-like structure.
      Solvophobic interaction between alkyl groups is the most important factor for the
      production of nanoscale heterogeneities, but electrostatic and hydrogen bonding
      attractions between the amine nitrogen and the nitrate anion will also play a
      role.

PMID- 18341332
TI  - Nucleophilic beta-oniovinylation: concept, mechanism, scope, and applications.
AB  - Insertion of an electron-deficient alkyne A-C[triple bond]C-A (A = CO2Me) into
      the C-L+ bond of an acyl-onio salt R-C(O)-L+ (R = Ar, OAlk; L = 4
      dimethylaminopyridine, PPh3) has for the first time been achieved in the presence
      of catalytic amounts of the nucleophile L. For R = OMe, a second insertion of the
      alkyne was observed. X-ray structures were obtained for a number of such beta
      oniovinylation products. Depending on reaction conditions, preferentially E- or Z
      stereochemistry was observed, the Z-isomer being the thermodynamically more
      stable. A mechanism for this novel insertion reaction is presented which accounts
      for the topology of the products and rationalizes the observed stereochemistry.
      The beta-onio-activated Michael systems thus generated represent a virtually
      unexplored class of compounds. The onio substituent in such compounds can be
      selectively replaced by a number of nucleophiles. Thus a series of Michael
      systems with donor functions in the beta-position is easily synthesized. These
      compounds represent a source for useful further transformations, for example,
      cyclizations to quinolones, thiochromones, and pyrazoles.

PMID- 18341333
TI  - Spectroscopic and electronic structure studies of symmetrized models for reduced
      members of the dimethylsulfoxide reductase enzyme family.
AB  - Enzymes belonging to the dimethylsulfoxide reductase (DMSOR) family of
      pyranopterin Mo enzymes have a unique active-site geometry in the reduced form
      that lacks a terminal oxo ligand, unlike the reduced active sites of other
      pyranopterin Mo enzymes. Furthermore, the DMSOR family is characterized by the
      coordination of two pyranopterin-ene-1,2-dithiolate ligands in their active
      sites, which is distinctive among the other pyranopterin Mo enzymes but analogous
      to all of the currently known tungsten-containing enzymes. Electronic absorption,
      resonance Raman, and ground- and excited-state density functional calculations of
      symmetrized analogues of the reduced DMSOR active site
      ([NEt4][Mo(IV)(QAd)(S2C2Me2)2] where Ad = 2-adamantyl; Q = O, S, Se) have allowed
      for a detailed description of Mo-bisdithiolene electronic structure in the
      absence of a strong-field oxo ligand. The electronic absorption spectra are
      dominated by dithiolene S --> Mo charge-transfer transitions, and the totally
      symmetric Mo-S Raman stretch is observed at approximately 400 cm(-1) for all
      three complexes. These data indicate that the Mo-bisdithiolene bonding scheme in
      high-symmetry [Mo(QAd)(S2C2Me2)2]- complexes is not strongly perturbed by the
      apical QAd- ligands, but instead, the dithiolene ligands define the t(2g) ligand
      field splitting. The effects of conserved geometric distortions observed in
      DMSOR, relative to these high-symmetry models, were explored by spectroscopically
      calibrated bonding calculations, and the results are discussed within the context
      of electronic structure contributions to ground-state destabilization and
      transition-state stabilization. The specific electronic structure tuning of the
      endogenous amino acid ligation on the mechanism of DMSOR is also discussed.

PMID- 18341334
TI  - DNA-templated polymerization of side-chain-functionalized peptide nucleic acid
      aldehydes.
AB  - The DNA-templated polymerization of synthetic building blocks provides a
      potential route to the laboratory evolution of sequence-defined polymers with
      structures and properties not necessarily limited to those of natural
      biopolymers. We previously reported the efficient and sequence-specific DNA
      templated polymerization of peptide nucleic acid (PNA) aldehydes. Here, we report
      the enzyme-free, DNA-templated polymerization of side-chain-functionalized PNA
      tetramer and pentamer aldehydes. We observed that polymerization of tetramer and
      pentamer PNA building blocks with a single lysine-based side chain at various
      positions in the building block could proceed efficiently and sequence
      specifically. In addition, DNA-templated polymerization also proceeded
      efficiently and in a sequence-specific manner with pentamer PNA aldehydes
      containing two or three lysine side chains in a single building block to generate
      more densely functionalized polymers. To further our understanding of side-chain
      compatibility and expand the capabilities of this system, we also examined the
      polymerization efficiencies of 20 pentamer building blocks each containing one of
      five different side-chain groups and four different side-chain regio- and
      stereochemistries. Polymerization reactions were efficient for all five different
      side-chain groups and for three of the four combinations of side-chain regio- and
      stereochemistries. Differences in the efficiency and initial rate of
      polymerization correlate with the apparent melting temperature of each building
      block, which is dependent on side-chain regio- and stereochemistry but relatively
      insensitive to side-chain structure among the substrates tested. Our findings
      represent a significant step toward the evolution of sequence-defined synthetic
      polymers and also demonstrate that enzyme-free nucleic acid-templated
      polymerization can occur efficiently using substrates with a wide range of side
      chain structures, functionalization positions within each building block, and
      functionalization densities.

PMID- 18341335
TI  - Structure, self-assembly, and dual role of a beta-defensin-like peptide from the
      Chinese soft-shelled turtle eggshell matrix.
AB  - Biomineral matrix formation and molecular recognition are two important processes
      associated with eggshell biomineralization. To understand these two processes, a
      major intracrystalline peptide, pelovaterin, was isolated from turtle (Pelodiscus
      sinensis) eggshell and its tertiary and quaternary structures were established.
      The global fold of pelovaterin is similar to that of human beta-defensins but has
      a large hydrophobic core and a short hydrophilic N-terminal segment, which is not
      preserved in defensins. Pelovaterin exhibits strong antimicrobial activity
      against two pathogenic gram-negative bacteria, Pseudomonas aeruginosa and Proteus
      vulgaris, and stabilizes a thin film of metastable vaterite. We show that
      pelovaterin self-aggregates in the form of micellar nanospheres and the
      aggregation in solution is entropy-driven. It is suggested that the micellar
      aggregation of pelovaterin is responsible for the induction and stabilization of
      the metastable phase by altering the interfacial energy. The results demonstrate
      the adaptability of an extracellular matrix protein to perform multiple tasks:
      polymorph discrimination and protection of the contents of the egg against
      bacterial invasion.

PMID- 18341336
TI  - Distinguishing between Dexter and rapid sequential electron transfer in
      covalently linked donor-acceptor assemblies.
AB  - The syntheses, physical, and photophysical properties of a family of complexes
      having the general formula [M2(L)(mcb)(Ru(4,4'-(X)2-bpy)2)](PF6)3 (where M =
      Mn(II) or Zn(II), X = CH3 or CF3, mcb is 4'-methyl-4-carboxy-2,2'-bipyridine, and
      L is a Schiff base macrocycle derived from 2,6-diformyl-4-methylphenol and bis(2
      aminoethyl)-N-methylamine) are described. The isostructural molecules all consist
      of dinuclear metal cores covalently linked to a Ru(II) polypyridyl complex.
      Photoexcitation of [Mn2(L)(mcb)(Ru((CF3)2-bpy)2)](PF6)3 (4) in deoxygenated
      CH2Cl2 solution results in emission characteristic of the 3MLCT excited state of
      the Ru(II) chromophore but with a lifetime (tau(obs) = 5.0 +/- 0.1 ns) and
      radiative quantum yield (Phi(r) approximately 7 x 10(-4)) that are significantly
      attenuated relative to the Zn(II) model complex [Zn2(L)(mcb)(Ru((CF3)2
      bpy)2)](PF6)3 (6) (tau(obs) = 730 +/- 30 ns and Phi(r) = 0.024, respectively).
      Quenching of the 3MLCT excited state is even more extensive in the case of
      [Mn2(L)(mcb)(Ru((CH3)2-bpy)2)](PF6)3 (3), whose measured lifetime (tau(obs) = 45
      +/- 5 ps) is >10(4) shorter than the corresponding model complex
      [Zn2(L)(mcb)(Ru((CH3)2-bpy)2)](PF6)3 (5) (tau(obs) = 1.31 +/- 0.05 micros). Time
      resolved absorption measurements on both Mn-containing complexes at room
      temperature revealed kinetics that were independent of probe wavelength; no
      spectroscopic signatures for electron-transfer photoproducts were observed. Time
      resolved emission data for complex 4 acquired in CH2Cl2 solution over a range of
      200-300 K could be fit to an expression of the form k(nr) = k0 + A x exp{
      DeltaE/kB T} with k0 = 1.065 +/- 0.05 x 10(7) s(-1), A = 3.7 +/- 0.5 x 10(10) s(
      1), and DeltaE = 1230 +/- 30 cm(-1). Assuming an electron-transfer mechanism, the
      variable-temperature data on complex 4 would require a reorganization energy of
      lambda approximately 0.4-0.5 eV which is too small to be associated with charge
      separation in this system. This result coupled with the lack of enhanced emission
      at temperatures below the glass-to-fluid transition of the solvent and the
      absence of visible absorption features associated with the Mn(II)2 core allows
      for a definitive assignment of Dexter transfer as the dominant excited-state
      reaction pathway. A similar conclusion was reached for complex 3 based in part on
      the smaller driving force for electron transfer (DeltaG0(ET) = -0.1 eV), the
      increase in probability of Dexter transfer due to the closer proximity of the
      donor excited state to the dimanganese acceptor, and a lack of emission from the
      compound upon formation of an optical glass at 80 K. Electronic coupling
      constants for Dexter transfer were determined to be approximately 10 cm(-1) and
      approximately 0.15 cm(-1) in complexes 3 and 4, respectively, indicating that the
      change in spatial localization of the excited state from the bridge (complex 3)
      to the periphery of the chromophore (complex 4) results in a decrease in
      electronic coupling to the dimanganese core of nearly 2 orders of magnitude. In
      addition to providing insight into the influence of donor/acceptor proximity on
      exchange energy transfer, this study underscores the utility of variable
      temperature measurements in cases where Dexter and electron-transfer mechanisms
      can lead to indistinguishable spectroscopic observables.

PMID- 18341337
TI  - Orientation of fluorinated cholesterol in lipid bilayers analyzed by 19F tensor
      calculation and solid-state NMR.
AB  - 6-F-cholesterol was reported to exhibit biological and interfacial properties
      similar to unmodified cholesterol. We have also found that 6-F-cholesterol
      mimicked the cholesterol activity observed in the systems of amphotericin B and
      lipid rafts. However, to use 6-F-cholesterol as a molecular probe to explore
      molecular recognition in membranes, it is indispensable to have detailed
      knowledge of the dynamic and orientation properties of the molecule in membrane
      environments. In this paper, we present the molecular orientation of 6-F
      cholesterol (30 mol %) in dimyristoylphosphatidylcholine (DMPC) bilayers revealed
      by combined use of 19F chemical shift anisotropy (CSA), 2H NMR, and C-F
      rotational echo double resonance (REDOR) experiments. The axis of rotation of 6-F
      cholesterol was shown to be in a similar direction to that of cholesterol in DMPC
      bilayers, which is almost parallel to the long axis of the molecular frame. The
      molecular order parameter of 6-F-cholesterol was determined to be ca. 0.85, which
      is within the range of reported values of cholesterol. These findings suggest
      that the dynamic properties of 6-F-cholesterol in DMPC are quite similar to those
      of unmodified cholesterol; therefore, the introduction of a fluorine atom at C6
      has virtually no effect on cholesterol dynamics in membranes. In addition, this
      study demonstrates the practical utility of theoretical calculations for
      determining the 19F CSA principal axes, which would be extremely difficult to
      obtain experimentally. The combined use of quantum calculations and solid-state
      19F NMR will make it possible to apply the orientation information of 19F CSA
      tensors to membrane systems.

PMID- 18341338
TI  - On-virus construction of polyvalent glycan ligands for cell-surface receptors.
AB  - Glycans arrayed on the exterior of virus particles were used as substrates for
      glycosyltransferase reactions to build di- and trisaccharides from the virus
      surface. The resulting particles exhibited tight and specific associations with
      cognate receptors on beads and cells, in one example defeating in cis cell
      surface interactions in a manner characteristic of polyvalent binding. Combined
      with the ability of viruses to provide structurally well-defined attachment
      points, the methodology provides a convenient and powerful way to prepare complex
      carbohydrate ligands for clustered receptors.

PMID- 18341339
TI  - Gas-phase thermochemistry of ruthenium carbene metathesis catalysts.
AB  - Quantitative energy-resolved collision-induced dissociation cross-sections by
      tandem ESI-MS provide absolute thermochemical data for phosphine binding energies
      in first- and second-generation ruthenium metathesis catalysts of 33.4 and 36.9
      kcal/mol, respectively. Furthermore a study of the ring-closing metathesis in the
      second-generation system to liberate norbornene by forming the 14-electron
      reactive intermediate from the intramolecular pi-complex gives an estimate of the
      olefin binding energy to the 14-electron complex of around 18 kcal/mol, assuming
      a loose transition state. The results reported here are in remarkably good
      agreement with the latest DFT calculations using the M06-L functional.

PMID- 18341340
TI  - Kinetic and thermodynamic characterization of Co(II)-substrate radical pair
      formation in coenzyme B12-dependent ethanolamine ammonia-lyase in a cryosolvent
      system by using time-resolved, full-spectrum continuous-wave electron
      paramagnetic resonance spectroscopy.
AB  - The formation of the Co(II)-substrate radical pair catalytic intermediate in
      coenzyme B12 (adenosylcobalamin)-dependent ethanolamine ammonia-lyase (EAL) from
      Salmonella typhimurium has been studied by using time-resolved continuous-wave
      electron paramagnetic resonance (EPR) spectroscopy in a cryosolvent system. The
      41% v/v DMSO/water cryosolvent allows mixing of holoenzyme and substrate, (S)-2
      aminopropanol, at 230 K under conditions of kinetic arrest. Temperature step from
      230 to 234-248 K initiates the cleavage of the cobalt-carbon bond and the
      monoexponential rise (rate constant, k(obs) = tau(obs)(-1)) of the EPR-detected
      Co(II)-substrate radical pair state. The detection deadtime: tau(obs) ratio is
      reduced by >10(2), relative to millisecond rapid mixing experiments at ambient
      temperatures. The EPR spectrum acquisition time is <tau(obs), which allows
      continuous acquisition of spectra during progress of the reaction. The k(obs)
      values and Co(II)-substrate radical pair amplitudes are independent of substrate
      concentration at each temperature. Therefore, the reaction occurs from the enzyme
      x coenzyme x substrate ternary complex. The constant value of the Co(II)
      substrate radical pair amplitude at reaction times >5tau(obs), the approximately
      10(2)-fold slower rate of the substrate radical rearrangement reaction relative
      to k(obs), and the reversible temperature dependence of the amplitude indicate
      that the Co(II)-substrate radical pair and ternary complex are essentially at
      equilibrium. The reaction is thus treated as a relaxation to equilibrium by using
      a linear two-step, three-state mechanism. The intermediate state in this
      mechanism, the Co(II)-5'-deoxyadenosyl radical pair, is not detected by EPR at
      signal-to-noise ratios of 10(3), which indicates that the free energy of the
      Co(II)-5'-deoxyadenosyl radical pair state is >3.3 kcal/mol, relative to the
      Co(II)-substrate radical pair. Van't Hoff analysis yields DeltaH13 = 10.8 +/- 0.8
      kcal/mol and DeltaS13 = 45 +/- 3 cal/mol/K for the transition from the ternary
      complex to the Co(II)-substrate radical pair state. The free energy difference,
      DeltaG13, is zero to within one standard deviation over the temperature range 234
      248 K. The extrapolated value of DeltaG13 at 298 K is -2.6 +/- 1.2 kcal/mol. The
      estimated EAL protein-associated contribution to the free energy difference is
      DeltaG(EAL) = -24 kcal/mol at 240 K, and DeltaH(EAL) = -13 kcal/mol and
      DeltaS(EAL) = 38 cal/mol/K. The results show that the EAL protein makes both
      strong enthalpic and entropic contributions to overcome the large, unfavorable
      cobalt-carbon bond dissociation energy, which biases the reaction in the forward
      direction of Co-C bond cleavage and Co(II)-substrate radical pair formation.

PMID- 18341341
TI  - Manganous phosphate acts as a superoxide dismutase.
AB  - A substantial body of evidence indicates that high intracellular concentrations
      of inorganic manganous ions render some cells resistant to ionizing radiation and
      provide substantial antioxidant protection to aerobic cells lacking superoxide
      dismutase (SOD) enzymes. We found that manganous phosphate is unique among those
      manganous salts studied in its ability to remove superoxide rapidly and
      catalytically from aqueous solution via a disproportionation mechanism that is
      entirely different from those of the SOD enzymes.

PMID- 18341342
TI  - Design, synthesis, and properties of 2',4'-BNA(NC): a bridged nucleic acid
      analogue.
AB  - The novel bridged nucleic-acid analogue 2',4'-BNA(NC) (2'-O,4'-C-aminomethylene
      bridged nucleic acid), containing a six-membered bridged structure with an N-O
      linkage, was designed and synthesized efficiently, demonstrating a one-pot
      intramolecular NC bond-forming key reaction to construct a perhydro-1,2-oxazine
      ring (11 and 12). Three monomers of 2',4'-BNA(NC) (2',4'-BNA(NC)[NH], [NMe], and
      [NBn]) were synthesized and incorporated into oligonucleotides, and their
      properties were investigated and compared with those of 2',4'-BNA (LNA)-modified
      oligonucleotides. Compared to 2',4'-BNA (LNA)-modified oligonucleotides, 2',4'
      BNA(NC) congeners were found to possess: (i) equal or higher binding affinity
      against an RNA complement with excellent single-mismatch discriminating power,
      (ii) much better RNA selective binding, (iii) stronger and more sequence
      selective triplex-forming characters, and (iv) immensely higher nuclease
      resistance, even higher than the S(p)-phosphorthioate analogue. 2',4'-BNA(NC)
      modified oligonucleotides with these excellent profiles show great promise for
      applications in antisense and antigene technologies.

PMID- 18341343
TI  - Solution structure of a DNA duplex containing a guanine-difluorotoluene pair: a
      wobble pair without hydrogen bonding?
AB  - The incorporation of synthetic nucleoside analogues into DNA duplexes provides a
      unique opportunity to probe both structure and function of nucleic acids. We used
      1H and 19F NMR and molecular dynamics calculations to determine the solution
      structures of two similar DNA decamer duplexes, one containing a central G-T
      mismatched or "wobble" base pair, and one in which the thymine in this base pair
      is replaced by difluorotoluene (a thymine isostere) creating a G-F pair. Here, we
      show that the non-hydrogen-bonding G-F pair stacks relatively well into the helix
      and that the distortions caused by each non-Watson-Crick G-T or G-F base pair are
      quite localized to a three base pair site around the mismatch. A detailed
      structural analysis reveals that the absence of hydrogen bonding introduces more
      dynamic motion into the G-F pair relative to G-T and permits the G-F pair to
      exhibit stacking and conformational features characteristic of both a Watson
      Crick base pair (on the guanine containing strand) and a wobble base pair (on the
      strand containing the difluorotoluene). We used these results to posit a
      rationale for recognition and repair of mismatch sites in DNA.

PMID- 18341344
TI  - Utilizing the lability of lead selenide to produce heterostructured nanocrystals
      with bright, stable infrared emission.
AB  - Infrared-emitting nanocrystal quantum dots (NQDs) have enormous potential as an
      enabling technology for applications ranging from tunable infrared lasers to
      biological labels. Notably, lead chalcogenide NQDs, especially PbSe NQDs, provide
      efficient emission over a large spectral range in the infrared, but their
      application has been limited by instability in emission quantum yield and peak
      position on exposure to ambient conditions. Conventional methods for improving
      NQD stability by applying a shell of a more stable, wider band gap semiconductor
      material are frustrated by the tendency of lead chalcogenide NQDs toward Ostwald
      ripening at even moderate reaction temperatures. Here, we describe a partial
      cation-exchange method in which we take advantage of this lability to
      controllably synthesize PbSe/CdSe core/shell NQDs. Critically, these NQDs are
      stable against fading and spectral shifting. Further, these NQDs can undergo
      additional shell growth to produce PbSe/CdSe/ZnS core/shell/shell NQDs that
      represent initial steps toward bright, biocompatible near-infrared optical
      labels.

PMID- 18341345
TI  - Organocatalytic asymmetric conjugate addition to allenic esters and ketones.
AB  - The first example of an organocatalytic enantioselective conjugate addition of
      cyclic beta-ketoesters and glycine imine derivatives to electron-deficient
      allenes is described. We disclose that the corresponding chiral beta,gamma
      unsaturated carbonyl compounds are formed exclusively under phase-transfer
      conditions using either cinchona-alkaloid-derived or biphenyl-based chiral
      quaternary ammonium salts as catalysts. The scope of the reaction for beta
      ketoesters is outlined for allenes having a ketone or ester motif as electron
      withdrawing group as well as different substituents in the 3-position, giving the
      optically active products in high yields and excellent diastereo- and
      enantioselectivities (90-96% ee). The conjugate addition also proceeds for a
      number of cyclic beta-ketoesters having different ring sizes, ring systems, and
      substituents in high yields and enantioselectivities. Glycine imine derivatives
      also undergo the asymmetric conjugate addition to electron-deficient allenes in
      high yields and with enantioselectivities in the range of 60-88% ee, thus
      providing a rapid entry to optically active alpha-vinyl-substituted alpha-amino
      acid derivatives. It is shown that the enantioselectivity is strongly dependent
      on the size of the ester moiety of the nucleophile in combination with the
      catalytic system used. The high synthetic value of the chiral products arising
      from these new catalytic processes is demonstrated by two straightforward
      transformations leading in one case to optically active hexahydrobenzopyranones
      and in the other to substituted pyroglutamates (gamma-lactames).

PMID- 18341346
TI  - Regio- and enantioselective catalytic cyclization of pyrroles onto N-acyliminium
      ions.
AB  - The regio- and enantioselective cyclization of pyrroles onto N-acyliminium ions
      generated in situ from hydroxylactams is reported. Modest to excellent ee's and
      yields are obtained in these novel Pictet-Spengler-type reactions with a chiral
      thiourea-pyrrole catalyst. Useful synthetic transformations of the versatile
      pyrroloindolizidinone and pyrroloquinolizidinone products are presented.

PMID- 18341347
TI  - Diastereomers of N-alpha-phenylethyl-t-butylsulfinamide: absolute configurations
      and predominant conformations.
AB  - N-alpha-Phenylethyl-t-butylsulfinamide is a complicated system for determining
      molecular stereochemistry because of numerous possibilities for assigning the
      absolute configuration and a predominant conformation. Two diastereomers of N
      alpha-phenylethyl-t-butylsulfinamide derived from (-)-(S)-alpha-phenylethyl
      amine, a (+)-diastereomer and a (-)-diastereomer, have been synthesized and their
      experimental chiroptical spectroscopic properties have been measured. These
      properties include vibrational circular dichroism, electronic circular dichroism
      and optical rotatory dispersion. Using these experimental data, in conjunction
      with corresponding density functional theoretical predictions, the absolute
      configuration and predominant conformations of these two diastereomers have been
      determined. Also, the absolute configuration of (-)-diastereomer has been
      independently confirmed by determining its structure from X-ray diffraction data.

PMID- 18341348
TI  - Synthesis of the potent anticancer agents ottelione A and ottelione B in both
      racemic and natural optically pure forms.
AB  - The powerful antitumor agents ottelione A and B were synthesized in racemic form
      by a method that relies on selective ring closing metathesis. Optically pure
      natural (+)-ottelione A was then made from d-ribose, via an alpha-keto
      cyclopropane. A key feature of the route is that the cyclopropyl group controls
      the stereochemistry in the attachment of the ArCH2 unit and is then converted by
      the action of SmI2 into a vinyl group, so that the substituents on the resulting
      five-membered ring have the required trans relationship. Epimerization of an
      intermediate gave access by the same method to the trans ring fused isomer (-)
      ottelione B.

PMID- 18341349
TI  - Design, synthesis, and photophysical characterization of water-soluble chlorins.
AB  - The use of chlorins as photosensitizers or fluorophores in a range of biological
      applications requires facile provisions for imparting high water solubility. Two
      free base chlorins have been prepared wherein each chlorin bears a geminal
      dimethyl group in the reduced ring and a water-solubilizing unit at the chlorin
      10-position. In one design (FbC1-PO3H2), the water-solubilizing unit is a 1,5
      diphosphonopent-3-yl ("swallowtail") unit, which has previously been used to good
      effect with porphyrins. In the other design (FbC2-PO3H2), the water-solubilizing
      unit is a 2,6-bis(phosphonomethoxy)phenyl unit. Two complementary routes were
      developed for preparing FbC2-PO3H2 that entail introduction of the protected
      phosphonate moieties either in the Eastern-half precursor to the chlorin or by
      derivatization of an intact chlorin. Water-solubilization is achieved in the last
      step of each synthesis upon removal of the phosphonate protecting groups. The
      chlorins FbC1-PO3H2 and FbC2-PO3H2 are highly water-soluble (>10 mM) as shown by
      1H NMR spectroscopy (D2O) and UV-vis absorption spectroscopy. The photophysical
      properties of the water-soluble chlorins in phosphate-buffered saline solution
      (pH 7.4) at room temperature were investigated using static and time-resolved
      absorption and fluorescence spectroscopic techniques. Each chlorin exhibits
      dominant absorption bands in the blue and the red region (lambda = 398, 626 nm),
      a modest fluorescence yield (Phi f approximately 0.11), a long singlet excited
      state lifetime (tau = 7.5 ns), and a high yield of intersystem crossing to give
      the triplet state (Phi isc = 0.9). The properties of the water-soluble chlorins
      in aqueous media are comparable to those of hydrophobic chlorins in toluene. The
      high aqueous solubility combined with the attractive photophysical properties
      make these compounds suitable for a wide range of biomedical applications.

PMID- 18341350
TI  - Synthesis and identification of heterocyclic derivatives of fullerene C60:
      unexpected reaction of anionic C60 with benzonitrile.
AB  - During the reaction of reduced C60 with benzyl bromide in benzonitrile, a novel
      cis-1 C60 adduct, 1,4-dibenzyl-2,3-cyclic phenylimidate C60 (1), was obtained
      rather than the expected product of 1,4-dibenzyl C60. The structure of compound 1
      was analyzed by X-ray single-crystal diffraction, identifying the presence of a
      five-membered heterocycle at a [5,6] bond of C60. One of the heteroatoms is
      assigned as a nitrogen atom; however, the identity of the other heteroatom cannot
      be determined unambiguously by crystallography due to similarity between the
      nitrogen and oxygen atoms. A related compound (2) bearing the same heterocycle
      was obtained from anionic C60 benzonitrile solution when no benzyl bromide was
      added. The structure of compound 2 was determined by NMR, MALDI FT-ICR MS, and UV
      vis. Results from MALDI FT-ICR MS for compound 2 show unambiguously that the
      second heteroatom is an oxygen atom, which is probably from traces of water in
      the solvent. Control experiments of the reactivity of the neutral, monoanionic,
      dianionic, and trianionic C60 have shown that the reactive species for the
      unexpected reaction is the C60 trianion.

PMID- 18341351
TI  - Synthesis of gamma-hydroxyalkyl substituted piperidine iminosugars from D
      glucose.
AB  - D-Glucose was converted to synthetic equivalent of meso-pentodialdose, namely 3-C
      (1'-aminoethyl)-alpha-d-ribo-pentodialdo-1,4-furanose 10 that gives an easy
      access to manipulate the aldehyde functionalities on either sides to get
      enantiomeric pair of 3. Thus, reduction of C5-aldehyde followed by hydrolysis of
      1,2-acetonide functionality and reductive aminocyclization with C1-aldehyde
      afforded gamma-1,2-dihydroxyethyl piperidine iminosugar 3. On the other hand,
      first reductive aminocyclization with C5-aldehyde gave piperidine ring skeleton
      12 that on removal of 1,2-acetonide and reduction of C1-aldehyde gave ent-3 while
      chopping of C1-aldehyde in 12 and reduction afforded gamma-hydroxymethyl
      piperidine iminosugar 4.

PMID- 18341352
TI  - Short alpha/beta-peptides as catalysts for intra- and intermolecular aldol
      reactions.
AB  - Short alpha/beta-peptides, containing conformationally restricted cis-beta
      aminocyclopropylcarboxylic acid units as turn-inducing elements, have been found
      to be efficient catalysts for inter- and intramolecular aldol reactions. The
      tripeptide H-(L)-Pro-black triangle-(L)-Pro-OH was identified to perform
      especially well in homogeneous and heterogeneous aqueous solutions as well as in
      organic solvents.

PMID- 18341353
TI  - Simultaneous determination of ozone and carbonyls using trans-1,2-bis(4
      pyridyl)ethylene as an ozone scrubber for 2,4-dinitrophenylhydrazine-impregnated
      silica cartridge.
AB  - A new method for the simultaneous determination of ozone and carbonyls in air
      using a two-bed cartridge system has been developed. Each bed consists of reagent
      impregnated silica particles. The first contains trans-1,2-bis-(4-pyridyl)
      ethylene (BPE) while the second contains 2,4-dinitrophenylhydrazine (DNPH). Air
      samples are drawn through the cartridge first through the BPE and then through
      the DNPH. Ozone in the air sample is trapped in the first bed by the BPE-coated
      silica particles and produce pyridine-4-aldehyde. Airborne carbonyls pass
      unimpeded thorough the BPE and are trapped in the second bed by the DNPH-coated
      silica particles. They produce carbonyl 2,4-DNPhydrazones. DNPH and carbonyl 2,4
      DNPhydrazones are not influenced by ozone because of effective trapping by the
      BPE. Extraction is performed in the direction reverse to air sampling. When
      solvent is eluted through the BEP/DNPH cartridge, excess DNPH is washed into the
      BPE bed where it reacted with pyridine-4-aldehyde and forms the corresponding
      hydrazone derivative. All of the hydrazones derived from airborne carbonyls and
      pyridine-4-aldehyde (derived from ozone) are completely separated and measured
      using high-performance liquid chromatography. An Ascentis RP-Amide column is
      used, and the mobile phase is 40% aqueous acetonitrile containing 2 mmol/L
      ammonium acetate. The use of a BPE/DNPH cartridge has made possible the
      simultaneous determination of ozone and carbonyls. A separate ozone scrubber is
      not necessary with the BPE/DNPH cartridge because the BPE portion of the sampler
      serves this function.

PMID- 18341354
TI  - Detecting D-amino acid-containing neuropeptides using selective enzymatic
      digestion.
AB  - Neuropeptides, gene products that undergo extensive post-translational
      modification (PTM), are frequently characterized using mass spectrometry (MS).
      One PTM in particular, the conversion of an L-amino acid to a D-amino acid, has
      no associated mass shift. Therefore, this PTM is difficult to evaluate using MS
      alone, especially in complex peptide mixtures. Here, enzymatic digestion using
      microsomal alanyl aminopeptidase is combined with MS characterization. This
      enzyme selectively degrades peptides lacking a D-amino acid in the second
      position from the N-terminus. By comparing a sample before and after digestion, D
      amino acid-containing peptides (DAACPs) present in small quantities in a complex
      mixture can be identified, even among much larger quantities of other non-DAACPs.
      Protocols that use microsomal alanyl aminopeptidase as a discovery-enabling agent
      are described and validated by identifying a known DAACP from the Aplysia
      californica abdominal ganglion.

PMID- 18341355
TI  - On-chip isoelectric focusing using photopolymerized immobilized pH gradients.
AB  - We present the first successful adaptation of immobilized pH gradients (IPGs) to
      the microscale (muIPGs) using a new method for generating precisely defined
      polymer gradients on-chip. Gradients of monomer were established via diffusion
      along 6 mm flow-restricted channel segments. Precise control over boundary
      conditions and the resulting gradient is achieved by continuous flow of stock
      solutions through side channels flanking the gradient segment. Once the desired
      gradient is established, it is immobilized via photopolymerization. Precise
      gradient formation was verified with spatial and temporal detection of a
      fluorescent dye added to one of the flanking streams. Rapid (<20 min) isoelectric
      focusing of several fluorescent pI markers and proteins is demonstrated across pH
      3.8-7.0 muIPGs using both denaturing and nondenaturing conditions, without the
      addition of carrier ampholytes. The muIPG format yields improved stability and
      comparable resolution to prominent on-chip IEF techniques. In addition to rapid,
      high-resolution separations, the reported muIPG format is amenable to multiplexed
      and multidimensional analysis via custom gradients as well as integration with
      other on-chip separation methods.

PMID- 18341356
TI  - Raman multiplexers for alternative gene splicing.
AB  - Nonfluorescent labels were used for an array-format multiplex detection of
      alternative splice junctions of breast cancer susceptibility gene 1 (BRCA1) by
      surface-enhanced Raman scattering (SERS). A four-plex detection scheme using
      nonfluorescent labels was demonstrated for DNA sequences specific to four BRCA1
      alternative splice variants: Delta(11q) (the last 3309 nt deleted from exon 11),
      Delta(9, 10) (exon 9 and 10 deleted), Delta(5) (exon 5 deleted), and Delta(5q, 6)
      (the last 22 nt of exon 5 and the entire exon 6 is deleted). This is the first
      proof-of-concept study to apply SERS-based detection using nonfluorescent labels
      to investigate alternative gene splicing. Detection sensitivity of up to 1 fM was
      demonstrated for the Raman labels chosen to clearly discriminate the splice
      junctions via specific target identification. The proposed approach has the
      potential to become a highly sensitive and selective tool for comprehensive
      alternative splicing profiling of BRCA1 or other genes relevant to specific
      diseases.

PMID- 18341357
TI  - Effective path length in attenuated total reflection spectroscopy.
AB  - Attenuated total reflection (ATR) spectroscopy is now the most popular sampling
      technique for the measurement of infrared spectra of condensed phase samples.
      Most practitioners of ATR spectroscopy use the equation for depth of penetration,
      d(p), to estimate the path length of the evanescent wave through the sample.
      However, the effective path length, d(e), of the evanescent wave in an ATR
      measurement, i.e., the equivalent path length in a transmission measurement that
      would lead to an absorption band of the same intensity, is a more accurate metric
      than d(p). In measurements designed to obtain the absorptivity of bands in the
      spectrum of a strongly absorbing viscous liquid, we have shown that the
      refractive index used in the expressions for d(e) must be modified to take into
      account the effect of anomalous dispersion before accurate effective path lengths
      and band absorptivities can be measured.

PMID- 18341358
TI  - Dynamic measurement of altered chemical messenger secretion after cellular uptake
      of nanoparticles using carbon-fiber microelectrode amperometry.
AB  - In this work, carbon-fiber microelectrode amperometry is used to characterize
      serotonin exocytosis from murine peritoneal mast cells cocultured with
      fibroblasts in the presence of Au nanoparticles. In the case of mast cell
      exposure to 1 nM 28 nm diameter spherical Au nanoparticles, there is a decrease
      of greater than 30% in the number of successful granule transport and fusion
      events, greater than 30% increase in the rate of intragranular matrix expansion,
      and greater than 20% increase in the number of secreted serotonin molecules per
      granule. These results suggest that nanoparticles interrupt the dense-core
      biopolymer intragranular matrix and present the potential for systematic studies
      showing how exocytotic function is influenced by nanoparticle size, shape, and
      composition.

PMID- 18341359
TI  - Interactions between chitosan and SDS at a low-charged silica substrate compared
      to interactions in the bulk--the effect of ionic strength.
AB  - The effect of ionic strength on association between the cationic polysaccharide
      chitosan and the anionic surfactant sodium dodecyl sulfate, SDS, has been studied
      in bulk solution and at the solid/liquid interface. Bulk association was probed
      by turbidity, electrophoretic mobility, and surface tension measurements. The
      critical aggregation concentration, cac, and the saturation binding of
      surfactants were estimated from surface tension data. The number of associated
      SDS molecules per chitosan segment exceeded one at both salt concentrations. As a
      result, a net charge reversal of the polymer-surfactant complexes was observed,
      between 1.0 and 1.5 mM SDS, independent of ionic strength. Phase separation
      occurs in the SDS concentration region where low charge density complexes form,
      whereas at high surfactant concentrations (up to several multiples of cmc SDS)
      soluble aggregates are formed. Ellipsometry and QCM-D were employed to follow
      adsorption of chitosan onto low-charged silica substrates, and the interactions
      between SDS and preadsorbed chitosan layers. A thin (0.5 nm) and rigid chitosan
      layer was formed when adsorbed from a 0.1 mM NaNO3 solution, whereas thicker (2
      nm) chitosan layers with higher dissipation/unit mass were formed from solutions
      at and above 30 mM NaNO3. The fraction of solvent in the chitosan layers was high
      independent of the layer thickness and rigidity and ionic strength. In 30 mM
      NaNO3 solution, addition of SDS induced a collapse at low concentrations, while
      at higher SDS concentrations the viscoelastic character of the layer was
      recovered. Maximum adsorbed mass (chitosan + SDS) was reached at 0.8 times the
      cmc of SDS, after which surfactant-induced polymer desorption occurred. In 0.1 mM
      NaNO3, the initial collapse was negligible and further addition of surfactant
      lead to the formation of a nonrigid, viscoelastic polymer layer until desorption
      began above a surfactant concentration of 0.4 times the cmc of SDS.

PMID- 18341360
TI  - Synthesis and characterization of an amphiphilic cyclodextrin, a micelle with two
      recognition sites.
AB  - A cyclodextrin derivative (Mod-CD) was synthesized through the monoesterification
      of beta-cyclodextrin (beta-CD) with 3-((E)-dec-2-enyl)-dihydrofuran-2,5-dione.
      The compound is an interesting surfactant that can form large aggregates not only
      through the interaction of the hydrophobic tails as in common amphiphilic
      compounds but also through the inclusion of the alkenyl chain into the cavity of
      another Mod-CD molecule. The self-inclusion of the chain in the cavity of
      cyclodextrin as well as the intermolecular inclusion was demonstrated by 1H NMR
      measurements that were able to detect methyl groups in three different
      environments. Besides, in the aggregates of Mod-CD, the cavity is available to
      interact with external guests such as phenolphthalein, 1-amino adamantane, and
      Prodan. Phenolphthalein has the same binding constant with Mod-CD and beta-CD,
      but the equilibrium constant for the interaction with Prodan is about 2 times
      larger for Mod-CD than for beta-CD. The latter result is attributed to the fact
      that this probe interacts with the micelle in two binding sites: the cavity of
      the cyclodextrin and the apolar heart of the micelle as evidenced by the
      spectrofluorimetric behavior of Prodan in solutions containing different
      concentrations of Mod-CD.

PMID- 18341361
TI  - Water penetration of damaged self-assembled monolayers.
AB  - The interaction of water with self-assembled monolayers (SAMs) on amorphous
      silica is investigated using classical molecular dynamics simulation. Damage is
      induced through shear simulations with model atomic force microscopy (AFM) tips
      and separately with controlled extraction. We find that SAM coatings that have
      been slightly damaged (by normal loads close to 10 nN from a 10-nm-diameter AFM
      tip) are susceptible to water penetration and migration to the underlying
      hydrophilic substrate. The controlled damage studies indicate that the presence
      of water tends to heal damage below a threshold radius and exploits and magnifies
      damage above this threshold. For the systems studied here, Si(OH)3(CH2)10CH3
      alkylsilane chains on amorphous silica, this threshold radius is between 0.5 and
      1.0 nm.

PMID- 18341362
TI  - Evaporative self-assembly from complex DNA-colloid suspensions.
AB  - Evaporation-induced pattern formation has attracted considerable attention as a
      simple yet versatile method for generating self-assembled structures that have
      broad applications from photonic devices to biomacromolecular recognition.
      Previous study of evaporative self-assembly has mainly focused on single
      nonvolatile component systems, and the driving mechanisms have been extensively
      investigated. In contrast, pattern formation from evaporating multicomponent
      systems, despite its wide existence in nature and numerous engineering
      applications, has been rarely explored. In this work, we examine a DNA-colloid
      binary suspension as a model system to understand the evaporation-induced
      interfacial hydrodynamics and self-assembled morphology in multicomponent systems
      involving complex competing intermolecular and interfacial interactions. Direct
      microscopic observations show that the composition of the binary system plays a
      critical role in the multiple-ring formation upon evaporation: (1) suspensions
      with high DNA concentrations and low colloidal concentrations favor the formation
      of the multiple-ring pattern; (2) the size of colloidal particles added into DNA
      aqueous droplets can significantly disrupt smooth multiple rings to form rippled
      rings and curtain-like periodic patterns with a curious spoke-like structure as
      the size of colloidal particles increases; and (3) the enhancement of DNA-colloid
      interaction by oppositely charged colloidal particles results in considerably
      high irregularity of DNA stain ring spacing. We examine the disruption of the
      multiring morphology under varied conditions and attribute it to local
      hydrodynamics governed by colloid aggregation and sedimentation. Our results
      demonstrate the feasibility of fabricating periodic self-assembled hybrid
      structures via one-step evaporation of droplets consisting of multiple
      components.

PMID- 18341363
TI  - Expeditious synthesis of water-soluble, monolayer-protected gold nanoparticles of
      controlled size and monolayer composition.
AB  - A protocol is reported for the preparation of water-soluble, thiol-protected Au
      nanoparticles (Au-MPC) where dioctylamine is used as a stabilizing agent when the
      gold cluster is formed using the two-phase Brust and Schiffrin procedure. The
      amount of amine controls the size of the nanoparticles in the 1.9-8.9 nm diameter
      range. The final stabilization of the gold clusters by addition of functionalized
      thiols is performed under very mild conditions compatible with most biomolecules.
      The procedure is suitable for a wide variety of functional groups present in the
      thiol and allows one to use thiol mixtures with a precise control of their
      composition in the monolayer. As a proof of principle, examples of nanoparticles
      protected with thiols comprising functional groups ranging from polyethers,
      saccharides, polyamines and ammonium ions are reported.

PMID- 18341364
TI  - Toxicological effect of ZnO nanoparticles based on bacteria.
AB  - Streptococcus agalactiae and Staphylococcus aureus are two pathogenetic agents of
      several infective diseases in humans. Biocidal effects and cellular
      internalization of ZnO nanoparticles (NPs) on two bacteria are reported, and ZnO
      NPs have a good bacteriostasis effect. ZnO NPs were synthesized in the EG aqueous
      system through the hydrolysis of ionic Zn2+ salts. Particle size and shape were
      controlled by the addition of the various surfactants. Bactericidal tests were
      performed in an ordinary broth medium on solid agar plates and in liquid systems
      with different concentrations of ZnO NPs. The biocidal action of ZnO materials
      was studied by transmission electron microscopy of bacteria ultrathin sections.
      The results confirmed that bactericidal cells were damaged after ZnO NPs
      contacted with them, showing both gram-negative membrane and gram-positive
      membrane disorganization. The surface modification of ZnO NPs causes an increase
      in membrane permeability and the cellular internalization of these NPs whereas
      there is a ZnO NP structure change inside the cells.

PMID- 18341365
TI  - Thermosensitive copolymer coatings with enhanced wettability switching.
AB  - Expanded cross-linked copolymers of poly(N-isopropylacrylamide) (PNiPAAm) and
      poly(acrylic acid) (PAAc) of varying monomer ratios were grafted from a
      crystalline silicon surface. Surface-tethered polymerization was performed at a
      slightly basic pH, where electrostatic repulsion among acrylic acid monomer units
      forces the network into an expanded polymer conformation. The influence of this
      expanded conformation on switchability between a hydrophilic and a hydrophobic
      state was investigated. Characterization of the copolymer coating was carried out
      by means of X-ray photoelectron spectroscopy (XPS) ellipsometry, and diffuse
      reflectance IR. Lower critical solution temperatures (LCSTs) of the copolymer
      grafts on the silicon surfaces were determined by spectrophotometry. Temperature
      induced wettability changes were studied using sessile drop contact angle
      measurements. The surface topography was investigated by atomic force microscopy
      (AFM) in Milli-Q water at 25 and 40 degrees C. The reversible attachment of a
      fluorescently labeled model protein was studied as a function of temperature
      using a fluorescence microscope and a fluorescence spectrometer. Maximum
      switching in terms of the contact angle change around the LCST was observed at a
      ratio of 36:1 PNiPAAm to PAAc. The enhanced control of biointerfaces achieved by
      these coatings may find applications in biomaterials, biochips, drug delivery,
      and microfluidics.

PMID- 18341366
TI  - Stick slip contact mechanics between dissimilar materials: effect of charging and
      large friction.
AB  - Measurements of the contact radius as a function of applied force between a mica
      surface and a silica surface (mica/silica) in air are reported. The load/unload
      results show that the contact radius generally increases with applied force.
      Because of the presence of charging due to contact electrification, both a short
      range van der Waals adhesion force and longer-range electrostatic adhesive
      interaction contribute to the measured force. The results indicate that
      approximately 20% of the pull-off force is due to van der Waals forces. The
      contact radius versus applied force results can be fit to Johnson-Kendall-Roberts
      (JKR) theory by considering that only the short-range van der Waals forces
      contribute to the work of adhesion and subtracting a constant longer-range
      electrostatic force. Also, an additional and unexpected step function is
      superimposed on the contact radius versus applied force curve. Thus, the contact
      diameter increases in a stepped dependence with increasing force. The stepped
      contact behavior is seen only for increasing force and is not observed when
      symmetric mica/mica or silica/silica contacts are measured. In humid conditions,
      the contact diameter of the mica/silica contact increases monotonically with
      applied force. Friction forces between the surfaces are also measured and the
      shear stress of a mica/silica interface is 100 times greater than the shear
      stress of a mica/mica interface. This large shear stress retards the increase in
      contact area as the force is increased and leads to the observed stepped contact
      mechanics behavior.

PMID- 18341367
TI  - Layer-by-layer self-assembly of multiwalled carbon nanotube polyelectrolytes
      prepared by in situ radical polymerization.
AB  - Anionic and cationic multiwalled carbon nanotube polyelectrolytes, prepared by
      covalent modification of multiwalled carbon nanotubes (MWCNTs) with poly(acrylic
      acid) and poly(acrylamide), were used for the layer-by-layer (LBL) self-assembly
      of MWCNTs on different substrates with polyelectrolytes, such as
      poly(diallyldimethylammonium chloride) and sodium poly(styrenesulfonate).
      Thermogravimetric analysis, Raman spectroscopy, and scanning electron microscopy
      (SEM) were used to demonstrate the modification of MWCNTs. Investigations using
      Fourier transform infrared spectroscopy, atomic force microscopy, SEM, and
      ultraviolet-visible spectroscopy proved this method to be practicable for
      preparing LBL films.

PMID- 18341368
TI  - Capillary condensation in porous materials. Hysteresis and interaction mechanism
      without pore blocking/percolation process.
AB  - We have performed measurements of boundary hysteresis loops, reversal curves, and
      subloops in p+-type porous silicon, a porous material composed of straight non
      interconnected pores. These data show that a strong interaction mechanism exists
      between the pores. The pores of porous silicon are non-independent, whereas they
      are not interconnected. This hysteretic behavior is very similar to that observed
      in porous glass, which consists of cavities connected to each other by
      constrictions. This questions the so-called pore blocking/percolation model
      developed to explain the behavior of fluid in porous glass. More generally, if we
      disregard the shape of the boundary hysteresis loops which depends on the porous
      material (H1 for MCM-41 and SBA-15, H2 for porous glass and p+-type porous
      silicon), the hysteretic features inside the main loop are qualitatively the same
      for all these porous systems. This shows that none of these systems are composed
      of independent pores. A coupling between the pores is always present whether they
      are interconnected or not and whatever the shape of the main loop is.

PMID- 18341369
TI  - Photochemical modification of an optical fiber tip with a silver nanoparticle
      film: a SERS chemical sensor.
AB  - We present a method of photochemical modification of an optical fiber tip with a
      silver nanoparticle film. The deposited silver nanoparticle film displays
      alternating light and dark circles, which are similar to a radial diffraction
      pattern. The modified optical fiber is examined as a chemical sensor for in situ
      detection. The modified fibers show excellent SERS activity, a low limit of
      detection (LOD), and good reproducibility. The maximum SERS activity of the
      sensor was achieved within 5.0 min of deposition. Thus, the method is also quite
      rapid.

PMID- 18341370
TI  - Synthesis, characterization, and antifouling potential of functionalized copper
      nanoparticles.
AB  - The synthesis, characterization, and antimicrobial properties of functionalized
      copper nanoparticle/polymer composites are reported. Copper nanoparticles (Cu
      NPs) are stabilized by surface attachment of the acrylic functionality that can
      be copolymerized with other acrylic monomers, thus, becoming an integral part of
      the polymer backbone. Biological experiments show that Cu NP/polymer composites
      exhibit antimicrobial activity similar to that of conventional copper-based
      biocides. Atomic absorption spectroscopy shows the smallest amount of copper ions
      leaching from chemically bound acrylated Cu NPs compared to the nonfunctionalized
      biocides. These composites have a strong potential for use in antibacterial or
      marine antifouling coatings.

PMID- 18341373
TI  - Luminescent cyclometalated Rh(III), Ir(III), and (DIP)2Ru(II) complexes with
      carboxylated bipyridyl ligands: synthesis, X-ray molecular structure, and
      photophysical properties.
AB  - Luminescent cyclometalated rhodium(III) and iridium(III) complexes of the general
      formula [M(ppy) 2(N (wedge)N)][PF 6], with N (wedge)N = Hcmbpy = 4-carboxy-4'
      methyl-2,2'-bipyridine and M = Rh ( 1), Ir ( 2) and N (wedge)N = H 2dcbpy = 4,4'
      dicarboxy-2,2'-bipyridine and M = Rh ( 3), Ir ( 4), were prepared in high yields
      and fully characterized. The X-ray molecular structure of the monocarboxylic
      iridium complex [Ir(ppy) 2(Hcmbpy)][PF 6] ( 2) was also determined. The
      photophysical properties of these compounds were studied and showed that the
      photoluminescence of rhodium complexes 1 and 3 and iridium complexes 2 and 4
      originates from intraligand charge-transfer (ILCT) and metal-to-ligand charge
      transfer/ligand-centered MLCT/LC excited states, respectively. For comparison
      purposes, the mono- and dicarboxylic acid ruthenium complexes [Ru(DIP)
      2(Hcmbpy)][Cl] 2 ( 5) and [Ru(DIP) 2(H 2dcbpy)][Cl] 2 ( 6), where DIP = 4,7
      diphenyl-1,10-phenanthroline, were also prepared, whose emission is MLCT in
      nature. Comparison of the photophysical behavior of these rhodium(III),
      iridium(III), and ruthenium(II) complexes reveals the influence of the carboxylic
      groups that affect in different ways the ILCT, MLCT, and LC states.

PMID- 18341374
TI  - Where do we stand with targeted therapy of refractory thyroid cancer?--Utility of
      RECIST criteria.

PMID- 18341375
TI  - The EUGOGO consensus statement on the management of Graves' orbitopathy: equally
      applicable to North American clinicians and patients.

PMID- 18341376
TI  - Altered intestinal absorption of L-thyroxine caused by coffee.
AB  - OBJECTIVE: To report eight case histories, and in vivo and in vitro studies
      showing coffee's potential to impair thyroxine (T4) intestinal absorption.
      DESIGN: Of eight women with inappropriately high or nonsuppressed thyroid
      stimulating hormone (TSH) when T4 was swallowed with coffee/espresso, six
      consented to the evaluation of their T4 intestinal absorption. This in vivo test
      was also administered to nine volunteers. In three separate tests, two 100 microg
      T4 tablets were swallowed with coffee, water, or water followed, 60 minutes
      later, by coffee. Serum T4 was assayed over the 4-hour period of the test. Two
      patients and two volunteers also agreed on having tested the intestinal
      absorption of T4 swallowed with solubilized dietary fibers. In the in vitro
      studies, classical recovery tests on known concentrations of T4 were performed in
      the presence of saline, coffee, or known T4 sequestrants (dietary fibers,
      aluminium hydroxide, and sucralfate). MAIN OUTCOME: For the in vivo test, average
      and peak incremental rise of serum T4 (AIRST4 and PIRST4), time of maximal
      incremental rise of serum T4 (TMIRST4), and area under the curve (AUC) were
      determined. In patients and volunteers, the four outcome measures were similar in
      the water and water + coffee tests. In patients and volunteers, compared to
      water, coffee lowered AIRST4 (by 36% and 29%), PIRST4 (by 30% and 19%), and AUC
      (by 36% and 27%) and delayed TMIRST4 (by 38 and 43 minutes); bran was a superior
      interferer. In the in vitro studies, coffee was weaker than known T4
      sequestrants. CONCLUSION: Coffee should be added to the list of interferers of T4
      intestinal absorption, and T4 to the list of compounds whose absorption is
      affected by coffee.

PMID- 18341377
TI  - Differentiated thyroid cancers 11-20 mm in diameter have clinical and
      histopathologic characteristics suggesting higher aggressiveness than those < or
      =10 mm.
AB  - OBJECTIVE: To compare characteristics and outcomes of differentiated thyroid
      cancers < or =10 mm with those 11-20 mm in diameter. DESIGN: Retrospective chart
      review of 426 patients with thyroid carcinoma < or =20 mm diagnosed and treated
      between 1990 and 2004 in one university clinic. MAIN OUTCOMES: Lymph node
      metastases were more frequent at diagnosis in 11-20 mm than in < or =10 mm
      cancers (p < 0.001). The prevalence of distant metastases did not differ between
      < or =10 mm and 11-20 mm cancers. One hundred and thirty-three patients (73%)
      with tumors 11-20 mm were disease free 2 years after 131I treatment, and no
      recurrence has been observed over 2-14 years of follow-up. Forty-one patients
      (22%) with cancers 11-20 mm (N1 or M1) required 2-4 years to become disease free.
      Neck lymph node recurrence was observed in nine patients (4.9%) 4 months to 14
      years after surgery and (131)I therapy. Four patients (1.6%) with cancers < or
      =10 mm in diameter had cancer recurrence (p = 0.05 compared to the 11-20 mm
      cancers). Based on the presence of distant metastases at diagnosis and recurrence
      of disease during follow-up, cancers 11-20 mm in diameter seemed more aggressive
      than those < or =10 mm (p < 0.05). CONCLUSION: Cancers 11-20 mm seem more
      aggressive than those < or =10 mm.

PMID- 18341378
TI  - Limited cytoprotective effects of amifostine in high-dose radioactive iodine 131
      treated well-differentiated thyroid cancer patients: analysis of quantitative
      salivary scan.
AB  - PURPOSE: The aim of present study was to investigate the cytoprotective effect of
      amifostine on salivary glands in 131I-treated differentiated thyroid cancer (DTC)
      patients using serial quantitative analysis of salivary gland scans. METHODS:
      Serial quantitative salivary scintigraphies were performed in 80 newly diagnosed
      DTC patients (9 men, 71 women; mean age, 43.2 years old; range, 21-58 years old).
      Forty-two patients were assigned randomly to the amifostine treatment group,
      which received 300 mg/m2 amifostine intravenously before 131I administration.
      RESULTS: In both amifostine-treated and nontreated groups statistically
      significant declines of functional parameters after 131I treatment were revealed
      by quantitative salivary scintigraphy in DTC patients. Amifostine pretreatment
      did not prevent the parenchymal damage to major salivary gland function after
      131I treatment (F = 1.37, p = 0.2461). However, the dose of 131I had significant
      effects on salivary gland function after 131I treatment (F = 9.72, p = 0.0002).
      CONCLUSION: The present study did not show cytoprotective effects of amifostine
      for DTC patients treated with 131I.

PMID- 18341379
TI  - Consensus statement of the European group on Graves' orbitopathy (EUGOGO) on
      management of Graves' orbitopathy.

PMID- 18341380
TI  - Reference values for spot urinary iodine concentrations in iodine-sufficient
      newborns using a new pad collection method.
AB  - BACKGROUND: Iodine deficiency in infancy can impair neurocognitive development,
      but there are few available indicators of iodine intake during this critical
      period. In many countries, access to newborns in maternity clinics in the first
      few days after birth is high. If spot urine samples could be collected, reference
      data for urinary iodine concentration (UIC) would be useful to evaluate their
      iodine status. The study objectives were 1) to develop and validate a simple pad
      system for collection of spot urine samples for iodine; 2) to establish a
      reference range for UIC in newborns in the first week after birth for use in
      monitoring iodine nutrition. METHODS: A two-stage cluster sampling was used to
      obtain a representative national sample of healthy, term Swiss infants, 0 to 5
      days old (n = 634). Gestational information, whole blood for thyrotropin, and
      spot urine samples on two consecutive days were collected. RESULTS: The pad
      collection system was well-accepted and performed well during recovery and
      contamination testing. Median UIC in the total sample (n = 1224) was 77 (95%
      confidence interval; 76, 81) microg/L; there was a gradual increase in median UIC
      within the range of 70-100 microg/L from days 1 through 4. Because urinary
      creatinine concentrations were high and variable, the UI:creatinine ratio was not
      useful for standardization. CONCLUSIONS: The current WHO median UIC cut-off (>
      100 microg/L) for iodine sufficiency in infancy may be too high for the first
      week after birth. Reference data from iodine-sufficient newborns and a simple
      collection system may facilitate use of UIC as an indicator of iodine status in
      this age group.

PMID- 18341381
TI  - Rhabdomyolysis, renal failure, pericardial effusion, and acquired von Willebrand
      disease resulting from hypothyroidism in a 10-year-old girl.
AB  - A 10-year-old girl manifested unexplained muscle aches and high creatine
      phosphokinase (CPK) concentrations attributed to rhabdomyolysis in association
      with severe hypothyroidism due to autoimmune thyroiditis. The response to therapy
      strongly suggested that hypothyroidism was the cause of rhabdomyolysis.
      Hypothyroidism is a rare cause of rhabdomyolysis. It should always be considered
      in a patient with muscular symptoms and elevated CPK concentrations. In addition,
      the patient developed other uncommon manifestations of hypothyroidism such as
      pericardial effusion, acute renal failure, and acquired von Willebrand disease.
      After thyroxine replacement, the symptoms and abnormal findings disappeared. The
      patient was also diagnosed as having celiac disease, which is often associated
      with autoimmune thyroiditis. Conditions accompanying autoimmune thyroid disease
      may result from altered thyroid function and from the presence of other
      autoimmune diseases. The butterfly-shaped thyroid gland has a tremendous impact
      on metabolism, which may be compared to a phenomenon termed the "Butterfly
      Effect".

PMID- 18341382
TI  - A six-year-old boy with a suspicious thyroid nodule: intrathyroidal thymic
      tissue.
AB  - BACKGROUND: Ectopic intrathyroidal thymus tissue that forms mass lesions as a
      consequence of aberrant thymic migration during embryogenesis is rarely reported
      in the literature. METHODS: We present the case of a 6-year-old boy with a right
      thyroid nodule and bilateral cervical lymph nodes. Thyroid hormone, antibodies,
      and routine chemistry tests were normal. Real-time thyroid ultrasound showed a
      right calcified nodule measuring 8 x 5 x 7 mm and multiple bilateral cervical
      lymph nodes. I131 scan showed mild decreased uptake in the right upper lobe. On
      fine-needle aspiration biopsy we discovered an atypical lymphoid proliferation
      that was suspicious, although not diagnostic, of a lymphoma. Immunostain for
      calcitonin was negative. Flow cytometry of the thyroid nodule aspirate
      demonstrated an abnormal polyclonal T cell population with dual expression of CD4
      and CD8, and a subpopulation of cells that expressed TdT suggesting the
      possibility of lymphoblastic lymphoma. DNA analysis, as well as polymerase chain
      reaction for T cell and B cell gene rearrangement, did not demonstrate changes in
      the gene for the heavy chain of immunoglobulin of B cells and gamma chain of the
      T cell receptor. Lymph node aspirate showed unremarkable T and B lymphoid cells.
      MAIN OUTCOMES: The diagnosis of ectopic intrathyroidal thymus was made after the
      operation. CONCLUSION: Ectopic thymus tissue should be considered in the
      differential diagnosis of thyroid masses, especially in children.

PMID- 18341383
TI  - Thyroid hemiagenesis associated with thyroid adenomatous hyperplasia and
      papillary thyroid carcinoma.

PMID- 18341385
TI  - Announcement of new features for Neurosurgical Focus.

PMID- 18341386
TI  - Shifting the balance: cell-based therapeutics as modifiers of the amyotrophic
      lateral sclerosis-specific neuronal microenvironment.
AB  - Recent advances in the laboratory have improved the current understanding of
      neurobiological mechanisms underlying the initiating events and pathological
      progression observed in amyotrophic lateral sclerosis (ALS). Whereas initial
      studies have revealed the late-stage intracellular cascades contributing to
      neuronal dysfunction and cell death, more recently collected data have begun to
      elucidate the presence and importance of a "non-cell autonomous" component
      indicating that affected glial cell subtypes may serve distinct and required
      roles. Pharmacological interventions for ALS have largely been disappointing
      likely in part because they have failed to address either the proximate events
      contributing to neuronal dysfunction and death or the deleterious contributions
      of non-neuronal cells within the local microenvironment. Alternatively, cell
      based therapeutics offer the potential of a multifaceted approach oriented toward
      the dual ends of protecting remaining viable neurons and attempting to restore
      neuronal function lost as a manifestation of disease progression. The authors
      review the evolving knowledge of disease initiation and progression, with
      specific emphasis on the role of affected glia as crucial contributors to the
      observed ALS phenotype. This basis is used to underscore the potential roles of
      cell-based therapeutics as modifiers of the ALS-specific microenvironment.

PMID- 18341388
TI  - Central nervous system therapy for lysosomal storage disorders.
AB  - Most lysosomal storage disorders are characterized by progressive central nervous
      system impairment, with or without systemic involvement. Affected individuals
      have an array of symptoms related to brain dysfunction, the most devastating of
      which is neurodegeneration following a period of normal development. The blood
      brain barrier has represented a significant impediment to developing therapeutic
      approaches to treat brain disease, but novel approaches-including enzyme
      replacement, small-molecule, gene, and cell-based therapies-have given children
      afflicted by these conditions and those who care for them hope for the future.

PMID- 18341387
TI  - Stem cell sources and therapeutic approaches for central nervous system and
      neural retinal disorders.
AB  - In the past decades, stem cell biology has made a profound impact on our views of
      mammalian development as well as opened new avenues in regenerative medicine. The
      potential of stem cells to differentiate into various cell types of the body is
      the principal reason they are being explored in treatments for diseases in which
      there may be dysfunctional cells and/or loss of healthy cells due to disease. In
      addition, other properties are unique to stem cells; their endogenous trophic
      support, ability to home to sites of pathological entities, and stability in
      culture, which allows genetic manipulation, are also being utilized to formulate
      stem cell-based therapy for central nervous system (CNS) disorders. In this
      review, the authors will review key characteristics of embryonic and somatic
      (adult) stem cells, consider therapeutic strategies employed in stem cell
      therapy, and discuss the recent advances made in stem cell-based therapy for a
      number of progressive neurodegenerative diseases in the CNS as well as neuronal
      degeneration secondary to other abnormalities and injuries. Although a great deal
      of progress has been made in our knowledge of stem cells and their utility in
      treating CNS disorders, much still needs to be elucidated regarding the biology
      of the stem cells and the pathogenesis of targeted CNS diseases to maximize
      therapeutic benefits. Nonetheless, stem cells present tremendous promise in the
      treatment of a variety of neurodegenerative diseases.

PMID- 18341389
TI  - Stroke repair with cell transplantation: neuronal cells, neuroprogenitor cells,
      and stem cells.
AB  - Stroke is a common cause of death and disability. The role of cellular
      transplantation to promote functional recovery has been explored. Preclinical
      studies first established the potential for cultured neuronal cells derived from
      a teratocarcinoma cell line to be tested for safety and efficacy in the treatment
      of human stroke. In animal models of stroke that caused reproducible learning and
      motor deficits, injection of neuronal cells resulted in a return of learning
      behavior retention time and motor function. In this report the authors review
      several current concepts for cellular repair, discuss important patient selection
      and surgical technique issues, and discuss plans for future experiments.

PMID- 18341390
TI  - Growth factors, stem cells, and stroke.
AB  - Postischemic neurogenesis has been identified as a compensatory mechanism to
      repair the damaged brain after stroke. Several factors are released by the
      ischemic tissue that are responsible for proliferation, differentiation, and
      migration of neural stem cells. An understanding of their roles may allow future
      therapies based on treatment with such factors. Although damaged cells release a
      variety of factors, some of them are stimulatory whereas some are inhibitory for
      neurogenesis. It is interesting to note that factors like insulin-like growth
      factor-I can induce proliferation in the presence of fibroblast growth factor-2
      (FGF-2), and promote differentiation in the absence of FGF-2. Meanwhile, factors
      like transforming growth factor-beta can induce the differentiation of neurons
      while inhibiting the proliferation of neural stem cells. Therefore, understanding
      the role of each factor in the process of neurogenesis will help physicians to
      enhance the endogenous response and improve the clinical outcome after stroke. In
      this article the authors discuss the role of growth factors and stem cells
      following stroke.

PMID- 18341391
TI  - Intravascular cell replacement therapy for stroke.
AB  - The use of stem cell transplantation to restore neurological function after
      stroke is being recognized as a potential novel therapy. Before stem cell
      transplantation can become widely applicable, however, questions remain about the
      optimal site of delivery and timing of transplantation. In particular, there
      seems to be increasing evidence that intravascular cell delivery after stroke is
      a viable alternative to intracerebral transplantation. In this review, the
      authors focus on the intravascular delivery of stem cells for stroke treatment
      with an emphasis on timing, transendothelial migration and possible mechanisms
      leading to neuroprotection, angiogenesis, immunomodulation, and neural
      plasticity. They also review current concepts of in vivo imaging and tracking of
      stem cells after stroke.

PMID- 18341392
TI  - Cell replacement therapy for intracerebral hemorrhage.
AB  - Intracerebral hemorrhage (ICH), for which no effective treatment strategy is
      currently available, constitutes one of the most devastating forms of stroke. As
      a result, developing therapeutic options for ICH is of great interest to the
      medical community. The 3 potential therapies that have the most promise are cell
      replacement therapy, enhancing endogenous repair mechanisms, and utilizing
      various neuroprotective drugs. Replacement of damaged cells and restoration of
      function can be accomplished by transplantation of cells derived from different
      sources, such as embryonic or somatic stem cells, umbilical cord blood, and
      genetically modified cell lines. Early experimental data showing the benefits of
      cell transplantation on functional recovery after ICH have been promising.
      Nevertheless, several studies have focused on another therapeutic avenue,
      investigating novel ways to activate and direct endogenous repair mechanisms in
      the central nervous system, through exposure to specific neuronal growth factors
      or by inactivating inhibitory molecules. Lastly, neuroprotective drugs may offer
      an additional tool for improving neuronal survival in the perihematomal area.
      However, a number of scientific issues must be addressed before these
      experimental techniques can be translated into clinical therapy. In this review,
      the authors outline the recent advances in the basic science of treatment
      strategies for ICH.

PMID- 18341393
TI  - Developing cell transplantation for temporal lobe epilepsy.
AB  - Mesial temporal lobe epilepsy (MTLE) is presumed to develop progressively as a
      consequence of synaptic reorganization and neuronal loss, although the exact
      etiology of seizure development is unknown. Nearly 30% of patients with MTLE have
      disabling seizures despite pharmacological treatment, and the majority of these
      patients are recommended for resection. The authors review cell transplantation
      as an alternative approach to the treatment of epilepsy. Recent work in animal
      models shows that grafted neuronal precursors that differentiate into inhibitory
      interneurons can increase the level of local inhibition. Grafts of these
      inhibitory neurons could help restore equilibrium in MTLE. Developing a sound
      transplantation strategy involves careful consideration of the etiology of MTLE
      and the expected functional role of transplanted cells. These issues are
      reviewed, with a focus on those factors most likely to influence clinically
      applicable results.

PMID- 18341395
TI  - Current status of experimental cell replacement approaches to spinal cord injury.
AB  - Despite advances in medical and surgical care, the current clinical therapies for
      spinal cord injury (SCI) are largely ineffective. During the last 2 decades, the
      search for new therapies has been revolutionized by the discovery of stem cells,
      which has inspired scientists and clinicians to search for a stem cell-based
      reparative approaches to many diseases, including neurotrauma. In the present
      study, the authors briefly summarize current knowledge related to the
      pathophysiology of SCI, including the concepts of primary and secondary injury
      and the importance of posttraumatic demyelination. Key inhibitory obstacles that
      impede axonal regeneration include the glial scar and a number of myelin
      inhibitory molecules including Nogo. Recent advancements in cell replacement
      therapy as a therapeutic strategy for SCI are summarized. The strategies include
      the use of pluripotent human stem cells, embryonic stem cells, and a number of
      adult-derived stem and progenitor cells such as mesenchymal stem cells, Schwann
      cells, olfactory ensheathing cells, and adult-derived neural precursor cells.
      Although current strategies to repair the subacutely injured cord appear
      promising, many obstacles continue to render the treatment of chronic injuries
      challenging. Nonetheless, the future for stem cell-based reparative strategies
      for treating SCI appears bright.

PMID- 18341394
TI  - Cell therapies for traumatic brain injury.
AB  - Preliminary discoveries of the efficacy of cell therapy are currently being
      translated to clinical trials. Whereas a significant amount of work has been
      focused on cell therapy applications for a wide array of diseases, including
      cardiac disease, bone disease, hepatic disease, and cancer, there continues to be
      extraordinary anticipation that stem cells will advance the current therapeutic
      regimen for acute neurological disease. Traumatic brain injury is a devastating
      event for which current therapies are limited. In this report the authors discuss
      the current status of using adult stem cells to treat traumatic brain injury,
      including the basic cell types and potential mechanisms of action, preclinical
      data, and the initiation of clinical trials.

PMID- 18341396
TI  - Stem cells and central nervous system therapeutics.

PMID- 18341397
TI  - Stem cell biology and its therapeutic applications in the setting of spinal cord
      injury.
AB  - The development of an acute traumatic spinal cord injury (SCI) inevitably leads
      to a complex cascade of ischemia and inflammation that results in significant
      scar tissue formation. The development of such scar tissue provides a severe
      impediment to neural regeneration and healing with restoration of function. A
      multimodal approach to treatment is required because SCIs occur with differing
      levels of severity and over different lengths of time. To achieve significant
      breakthroughs in outcomes, such approaches must combine both neuroprotective and
      neuroregenerative treatments. Novel techniques modulating endogenous stem cells
      demonstrate great promise in promoting neuroregeneration and restoring function.

PMID- 18341398
TI  - Stem cell-mediated regeneration of the intervertebral disc: cellular and
      molecular challenge.
AB  - Regenerative medicine and stem cells hold great promise for intervertebral disc
      (IVD) disease. The therapeutic implications of utilizing stem cells to repair
      degenerated discs and treat back pain are highly anticipated by both the clinical
      and scientific communities. Although the avascular environment of the IVD poses a
      challenge for stem cell-mediated regeneration, neuroprogenitor cells have been
      discovered within degenerated discs, allowing scientists to revisit the hostile
      environment of the IVD as a target for stem cell therapy. Issues now under
      investigation include the timing of cell delivery and manipulation of stem cells
      to make them more efficient and adaptive in the IVD niche. This review covers the
      mechanisms underlying disc degeneration as well as the molecular and cellular
      challenges involved in directing stem cells to the desired cell type for
      intradiscal transplantation.

PMID- 18341399
TI  - Cellular therapy for childhood neurodegenerative disease. Part I: rationale and
      preclinical studies.
AB  - Successful cellular replacement in the diseased human central nervous system
      (CNS) faces numerous hurdles. In this first installment of a 2-part review, the
      authors report on the preclinical challenges involved in preparing for a major
      Phase I trial investigating the safety of human neural stem cell transplantation
      in a lysosomal storage disorder. Specifically, they discuss choice of the ideal
      disease for treatment, best donor cell type and source for implantation, the in
      vitro and in vivo methods used to estimate safety and efficacy, the challenges to
      noninvasive tracking of cells after transplantation, and the unique issues
      related to the immunology of CNS cellular transplantation.

PMID- 18341400
TI  - Cellular therapy for childhood neurodegenerative disease. Part II: clinical trial
      design and implementation.
AB  - Cellular replacement therapy attempts to improve functioning of the diseased
      human central nervous system (CNS). In this second installment of a 2-part
      review, the authors discuss the major challenges to the translation of in vitro
      and animal studies of neural stem cell (NSC) therapy in the clinical setting.
      This analysis details the problems unique to the design of clinical trials using
      human NSCs, outlines patient selection practices, describes surgical techniques
      for cellular transplantation, and reviews the regulatory issues and ethical
      concerns in trials involving neurologically impaired children.

PMID- 18341401
TI  - Stem cells: new frontiers of ethics, law, and policy.
AB  - After the successful isolation of human embryonic stem cells in 1998, ethics and
      policy debates centered on the moral status of the embryo-whether the 2- to 4-day
      old blastocyst is a person, and whether we should protect it at all costs. As the
      research has moved quickly forward, however, new questions have emerged for the
      study of stem cell ethics, law, and policy. Powerful new lines made without eggs
      or embryos have recently been reported, the intellectual property and regulatory
      environment is uncertain, and clinical trials using adult stem cells and cells
      derived from embryonic stem cells are about to commence. The new landscape of
      ethics, law, and policy is discussed in the context of these developments, with
      an emphasis on the evaluation of risks and benefits for first-in-human clinical
      studies.

PMID- 18341402
TI  - Molecular and cell biology of brain tumor stem cells: lessons from neural
      progenitor/stem cells.
AB  - The results of studies conducted in the past several years have suggested that
      malignant brain tumors may harbor a small fraction of tumor-initiating cells that
      are likely to cause tumor recurrence. These cells are known as brain tumor stem
      cells (BTSCs) because of their multilineage potential and their ability to self
      renew in vitro and to recapitulate original tumors in vivo. The understanding of
      BTSCs has been greatly advanced by knowledge of neural progenitor/stem cells
      (NPSCs), which are multipotent and self-renewing precursor cells for neurons and
      glia. In this article, the authors summarize evidence that genetic mutations that
      deregulate asymmetric cell division by affecting cell polarity, spindle
      orientation, or cell fate determinants may result in the conversion of NPSCs to
      BTSCs. In addition, they review evidence that BTSCs and normal NPSCs may reside
      in similar vascularized microenvironments, where similar evolutionarily conserved
      signaling pathways control their proliferation. Finally, they discuss preliminary
      evidence that mechanisms of BTSC-associated infiltrativeness may be similar to
      those underlying the migration of NPSCs and neurons.

PMID- 18341403
TI  - Biology of brain tumor stem cells.

PMID- 18341404
TI  - Brain tumor stem cells and the tumor microenvironmen.
AB  - Recent advances in stem cell research and developmental neurobiology have
      uncovered new perspectives from which to investigate various forms of cancer.
      Specifically, the hypothesis that tumors consist of a subpopulation of malignant
      cells similar to stem cells is of great interest to scientists and clinicians and
      has been dubbed the "cancer stem cell hypothesis." The region in which this
      assertion is most relevant is within the brain. Cancer stem cells have been
      isolated from brain tumors that exhibit characteristics of differentiation and
      proliferation normally seen only in neural stem cells. These cancer stem cells
      may be responsible for tumor origin, survival, and proliferation. Furthermore,
      these cells must be considered within their immediate microenvironment when
      investigating mechanisms of tumorigenesis. Evidence of brain tumor stem cells is
      reviewed along with the role of tumor environment as the context within which
      these cells should be understood.

PMID- 18341405
TI  - New strategy for the analysis of phenotypic marker antigens in brain tumor
      derived neurospheres in mice and humans.
AB  - OBJECT: Brain tumor stem cells (TSCs) hypothetically drive the malignant
      phenotype of glioblastoma multiforme (GBM), and evidence suggests that a better
      understanding of these TSCs will have profound implications for treating gliomas.
      When grown in vitro, putative TSCs grow as a solid sphere, making their
      subsequent characterization, particularly the cells within the center of the
      sphere, difficult. Therefore, the purpose of this study was to develop a new
      method to better understand the proteomic profile of the entire population of
      cells within a sphere. METHODS: Tumor specimens from patients with confirmed GBM
      and glioma models in mice were mechanically and enzymatically dissociated and
      grown in traditional stem cell medium to generate neurospheres. The neurospheres
      were then embedded in freezing medium, cryosectioned, and analyzed with
      immunofluorescence. RESULTS: By sectioning neurospheres as thinly as 5 mum, the
      authors overcame many of the problems associated with immunolabeling whole
      neurospheres, such as antibody penetration into the core of the sphere and
      intense background fluorescence that obscures the specificity of
      immunoreactivity. Moreover, the small quantity of material required and the speed
      with which this cryosectioning and immunolabeling technique can be performed make
      it an attractive tool for the rapid assessment of TSC character. CONCLUSIONS:
      This study is the first to show that cryosectioning of neurospheres derived from
      glioma models in mice and GBM in humans is a feasible method of better defining
      the stem cell profile of a glioma.

PMID- 18341406
TI  - Human embryonic stem cells: a potential source of transplantable neural
      progenitor cells.
AB  - The primary therapeutic goal of embryonic stem cell (ESC) research is cell
      replacement therapy. During the last decade, great strides have been made in
      developing in vitro protocols for differentiating human ESCs into neuroepithelial
      progenitors. More recent progress has been made in further directing them into
      becoming cells with specialized regional and neurotransmitter identities, such as
      midbrain dopaminergic and spinal motor neurons. Along with directed
      differentiation, other current efforts are aimed at efficient enrichment,
      avoidance of immune rejection, demonstration of functional integration, genetic
      modification to regulate neurotransmitter and factor release, directed axon
      growth, in vivo cell tracking, and measures to ensure safety. This review will
      focus on the potential of ESCs as a source of transplantable cells for use in
      cell replacement therapy.

PMID- 18341407
TI  - Generation of embryonic stem cells: limitations of and alternatives to inner cell
      mass harvest.
AB  - Embryonic stem (ES) cells are pluripotent cells derived from the inner cell mass
      of the early mammalian embryo. Because of their plasticity and potentially
      unlimited capacity for self-renewal, ES cells have generated tremendous interest
      both as models for developmental biology and as possible tools for regenerative
      medicine. This excitement has been attenuated, however, by scientific, political,
      and ethical considerations. In this article the authors describe somatic cell
      nuclear transfer and transcription-induced pluripotency, 2 techniques that have
      been used in attempts to circumvent the need to derive ES cells by the harvest of
      embryonic tissue.

PMID- 18341408
TI  - Inhibition of oligodendrocyte precursor cell differentiation by myelin-associated
      proteins.
AB  - OBJECT: Promoting repair of central nervous system (CNS) white matter represents
      an important approach to easing the course of a number of tragic neurological
      diseases. For this purpose, strategies are currently being evaluated for
      transplanting cells capable of generating new oligodendrocytes into areas of
      demyelination and/or enhancing the potential of endogenous stem/precursor cells
      to give rise to new oligodendrocytes. Emerging evidence, however, indicates that
      increasing the presence of cells capable of forming new myelin sheaths is not
      sufficient to promote repair because of unknown inhibitors that accumulate in
      lesions as a consequence of myelin degeneration and impair the generation of new
      oligodendrocytes. The aim of the present study was to characterize the nature of
      the inhibitory molecules present in myelin. METHODS: Differentiation of primary
      rat oligodendrocyte precursor cells (OPCs) in the presence of CNS and peripheral
      nervous system myelin was assessed by immunocytochemical methods. The authors
      further characterized the nature of the inhibitors by submitting myelin membrane
      preparations to biochemical precipitation and digestion. Finally, OPCs were grown
      on purified Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated
      glycoprotein, the most prominent inhibitors of axon regeneration. RESULTS: Myelin
      membrane preparations induced a differentiation block in OPCs that was associated
      with down-regulation of expression of the transcription factor Nkx2.2. The
      inhibitory activity in myelin was restricted to the CNS and was predominantly
      associated with white matter. Furthermore, the results demonstrate that myelin
      proteins that are distinct from the most prominent inhibitors of axon outgrowth
      are specific inhibitors of OPC differentiation. CONCLUSIONS: The inhibitory
      effect of unknown myelin-associated proteins should be considered in future
      treatment strategies aimed at enhancing CNS repair.

PMID- 18341409
TI  - Recent advances in cell-based therapy for Parkinson disease.
AB  - In this review, the authors discuss recent advances in the field of cell therapy
      for Parkinson disease (PD). They compare and contrast recent clinical trials
      using fetal dopaminergic neurons. They attribute differences in cell preparation
      techniques, cell type specification, and immunosuppression as reasons for
      variable outcome and for some of the side effects observed in these clinical
      trials. To address ethical, practical, and technical issues related to the use of
      fetal cell sources, alternative sources of therapeutic dopaminergic neurons are
      being developed. The authors describe the progress in enrichment and purification
      strategies of stem cell-derived dopaminergic midbrain neurons. They conclude that
      recent advances in cell therapy for PD will create a viable long-term treatment
      option for synaptic repair for this debilitating disease.

PMID- 18341410
TI  - Cell-based therapy for Parkinson disease.

PMID- 18341411
TI  - Survival, differentiation, and migration of bioreactor-expanded human neural
      precursor cells in a model of Parkinson disease in rats.
AB  - OBJECT: Fetal tissue transplantation for Parkinson disease (PD) has demonstrated
      promising results in experimental and clinical studies. However, the widespread
      clinical application of this therapeutic approach is limited by a lack of fetal
      tissue. Human neural precursor cells (HNPCs) are attractive candidates for
      transplantation because of their long-term proliferation activity. Furthermore,
      these cells can be reproducibly expanded in a standardized fashion in suspension
      bioreactors. In this study the authors sought to determine whether the survival,
      differentiation, and migration of HNPCs after transplantation depended on the
      region of precursor cell origin, intracerebral site of transplantation, and
      duration of their expansion. METHODS: Human neural precursor cells were isolated
      from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of
      human fetuses 8-10 weeks of gestational age, and their differentiation potential
      characterized in vitro. After expansion in suspension bioreactors, the HNPCs were
      transplanted into the striatum and substantia nigra of parkinsonian rats.
      Histological analyses were performed 7 weeks posttransplantation. RESULTS: The
      HNPCs isolated from various regions of the neuraxis demonstrated diverse
      propensities to differentiate into astrocytes and neurons and could all
      successfully expand under standardized conditions in suspension bioreactors. At 7
      weeks posttransplantation, survival and migration were significantly greater for
      HNPCs obtained from the more rostral brain regions. The HNPCs differentiated
      predominantly into astrocytes after transplantation into the striatum or
      substantia nigra regions, and thus no behavioral improvement was observed.
      CONCLUSIONS: Understanding the regional differences in HNPC properties is
      prerequisite to their application for PD cell restoration strategies.

PMID- 18341412
TI  - Cell therapy in Huntington disease.
AB  - Huntington disease (HD), caused by polyglutamate expansions in the huntingtin
      protein, is a progressive neurodegenerative disease resulting in cognitive and
      motor impairments and death. Neuronal dysfunction and degeneration contribute to
      progressive physiological, motor, cognitive, and emotional disturbances
      characteristic of HD. A major impetus for research into the treatment of HD has
      centered on cell therapy strategies to protect vulnerable neuronal cell
      populations or to replace dysfunctional or dying cells. The work underlying 3
      approaches to HD cell therapy includes the potential for self-repair through the
      manipulation of endogenous stem cells and/or neurogenesis, the use of fetal or
      stem cell transplantation as a cell replacement strategy, and the administration
      of neurotrophic factors to protect susceptible neuronal populations. These
      approaches have shown some promising results in animal models of HD. Although
      striatal transplantation of fetal-derived cells has undergone clinical assessment
      since the 1990s, many cell therapy strategies have yet to be applied in the
      clinic environment. A more thorough understanding of the pathophysiologies
      underlying HD as well as the response of both endogenous and exogenous cells to
      the degenerating brain will inform their merit as potential therapeutic agents
      and enhance the framework by which the success of such strategies are determined.

PMID- 18341413
TI  - A new method for hemorrhoid surgery: experimental model of diode laser
      application in monkeys.
AB  - OBJECTIVE: Detailed here is an experimental model in monkeys of a new approach to
      treat hemorrhoids using a diode laser. BACKGROUND DATA: Hemorrhoids are a common
      source of pain and suffering. Endovascular laser therapy for variceal veins is a
      method that potentially could be used in the treatment of hemorrhoids. There is
      currently no such method described in the literature. MATERIALS AND METHODS:
      Hemorrhoids were induced in monkeys by ligation of the inferior hemorrhoidal
      vein, similar to their cause in humans. After the piles were identified, laser
      fibers were introduced into them, and they were irradiated with laser energy (810
      nm at 1-2 W in 1-sec pulses of 1-2 J each, for a total fluency of 4-10 J).
      RESULTS: The piles were completely reduced, and histological examination
      performed 10 d post-surgery showed reduction of the dilated vessels and complete
      healing. The laser energy was not delivered directly into the veins, but instead
      to the surrounding submucosal interstitial tissue, effectively reducing the
      hemorrhoids. CONCLUSION: The diode laser energy delivered into the hemorrhoids
      led to their complete resolution. Further clinical trials using this protocol
      must be carried out to determine its applicability to human hemorrhoids.

PMID- 18341414
TI  - Evaluation of patient perceptions of frenectomy: a comparison of Nd:YAG laser and
      conventional techniques.
AB  - OBJECTIVE: The aim of the randomized controlled clinical trial described here was
      to determine the anxiety levels of patients prior to frenectomy using the Nd:YAG
      laser and conventional technique, and to compare the effects of these two methods
      on the degree of postoperative pain, discomfort, and functional complications
      (eating and speech). METHODS: Forty patients with mucogingival problems due to
      labial frenums (both maxillary and mandibular) were included in the study.
      Ratings of preoperative fear and postoperative pain and functional complications
      for each patient were recorded using a visual analog scale at 3 h, 1 d, and 1 wk
      post-surgery. RESULTS: The results indicated that patients treated with the
      Nd:YAG laser had less postoperative pain and fewer functional complications (p <
      0.05). CONCLUSION: The results suggest that in the population studied, Nd:YAG
      laser treatment of soft tissue disorders provides better patient perceptions of
      success than those seen with conventional surgery.

PMID- 18341415
TI  - Laser-assisted anterior cervical corpectomy versus posterior laminoplasty for
      cervical myelopathic patients with multilevel ossification of the posterior
      longitudinal ligament.
AB  - OBJECTIVE: This study reports on the comparative results of a series of patients
      with multilevel cervical ossification of the posterior longitudinal ligament
      (OPLL) who were treated with laser-assisted anterior corpectomy or laminoplasty.
      METHODS: Forty-eight patients (21 patients with anterior corpectomy and 27
      patients with laminoplasty) with cervical OPLL involvement of three or more
      vertebral bodies were retrospectively reviewed. Both pre- and postoperatively
      neurological status was graded according to the Nurick grading system. The
      anteroposterior (AP) diameter change at the narrowest part of the spinal canal,
      the change in the regional and the overall cervical Cobb's angle, and the change
      in cervical range of motion (ROM) were all measured. The mean follow-up periods
      were 21.8 mo and 29.1 mo for the corpectomy and laminoplasty patients,
      respectively. RESULTS: The mean changes in the pre- to postoperative Nurick
      grades were 1.9 for the corpectomy group and 1 for the laminoplasty group (p <
      0.05). The mean changes in the pre- to postoperative spinal canal AP diameters
      were 9.1 mm and 4.11 mm, respectively, for the corpectomy group and the
      laminoplasty group (p < 0.05). The mean changes of the regional Cobb's angle were
      1.7 degrees and -3.1 degrees (p = 0.06), and the mean changes of the overall
      cervical Cobb's angle were 1.1 degrees and -1.6 degrees , respectively, for the
      corpectomy group and the laminoplasty group (p > 0.05). The changes in the
      cervical degree of ROM were -19.6 degrees and -19.7 degrees , respectively, for
      the corpectomy group and the laminoplasty group (p > 0.05). CONCLUSIONS: Direct
      decompression of the spinal cord by laser-assisted anterior cervical corpectomy
      was shown to be a better surgical option on long-term follow-up, yielding more
      recovery of neurological deficits, achieving adequate decompression of the spinal
      canal, and preventing the development of regional kyphosis at the operated level
      of the spine, in patients with multilevel cervical OPLL.

PMID- 18341416
TI  - Diagnosis of ovarian cancer by Raman spectroscopy: a pilot study.
AB  - OBJECTIVE: To assess the efficacy of conventional Raman spectroscopy in
      combination with discriminating parameters, Mahalanobis distance, spectral
      residuals, and "limit test" methodology in differentiation of normal and
      malignant ovarian tissues. BACKGROUND DATA: Ovarian cancer is the second most
      common cancer among women and the leading cause of death among gynecologic
      malignancies. Initial laparotomy and subsequent frozen section analysis can
      influence the surgical management of ovarian cancers. Although frozen section
      pathology is sensitive and specific enough, interpretation is often subjective,
      time consuming, and requires highly skilled personnel. Raman spectroscopy is
      sensitive to biochemical variations in the samples, rapid, more objective, and
      amenable to multivariate statistical tools. It can therefore be an ideal tool for
      discrimination between normal and malignant ovarian tissues. METHODS: 72 Spectra
      from eight normal and seven malignant ovarian tissues were recorded by
      conventional near-infrared (NIR) Raman spectroscopy (excitation wavelength of 785
      nm). Spectral data were analyzed by principal components analysis (PCA) and other
      discriminating parameters such as Mahalanobis distance, spectral residuals, and a
      multiparametric limit test approach. RESULTS: A mean malignant spectrum exhibits
      a broader amide I band, a stronger amide III band, a minor blue shift in the
      delta CH2 band, and a hump around 1480 cm(-1) compared to a normal spectrum. The
      normal spectra show relatively stronger peaks around the 855 and 940 cm(-1)
      region. Scores of factor 1 as well as Mahalanobis distance and spectral residuals
      gave good classification among the tissue types. The limit test approach provided
      unambiguous and objective discrimination. CONCLUSION: The findings of this study
      demonstrate the efficacy of conventional Raman spectroscopy and our statistical
      methodologies in discrimination of normal from malignant ovarian tissues.
      Prospectively, by evaluating the models and developing suitable fiberoptic
      probes, this technique could be useful in diagnosis during initial laparotomy.

PMID- 18341417
TI  - Low-power laser treatment in patients with frozen shoulder: preliminary results.
AB  - OBJECTIVE: In this study I sought to test the efficacy of low-power laser therapy
      (LLLT) in patients with frozen shoulder. BACKGROUND DATA: The use of low-level
      laser energy has been recommended for the management of a variety of
      musculoskeletal disorders. MATERIALS AND METHODS: Sixty-three patients with
      frozen shoulder were randomly assigned into one of two groups. In the active
      laser group (n = 31), patients were treated with a 810-nm Ga-Al-As laser with a
      continuous output of 60 mW applied to eight points on the shoulder for 30 sec
      each, for a total dose of 1.8 J per point and 14.4 J per session. In the placebo
      group (n = 32), patients received placebo laser treatment. During 8 wk of
      treatment, the patients in each group received 12 sessions of laser or placebo,
      two sessions per week (for weeks 1-4), and one session per week (for weeks 5-8).
      RESULTS: Relative to the placebo group, the active laser group had: (1) a
      significant decrease in overall, night, and activity pain scores at the end of 4
      wk and 8 wk of treatment, and at the end of 8 wk additional follow-up (16 wk post
      randomization); (2) a significant decrease in shoulder pain and disability index
      (SPADI) scores and Croft shoulder disability questionnaire scores at those same
      intervals; (3) a significant decrease in disability of arm, shoulder, and hand
      questionnaire (DASH) scores at the end of 8 wk of treatment, and at 16 wk
      posttreatment; and (4) a significant decrease in health-assessment questionnaire
      (HAQ) scores at the end of 4 wk and 8 wk of treatment. There was some improvement
      in range of motion, but this did not reach statistical significance. CONCLUSIONS:
      The results suggested that laser treatment was more effective in reducing pain
      and disability scores than placebo at the end of the treatment period, as well as
      at follow-up.

PMID- 18341418
TI  - Computer-guided CO2-laser osteotomy of the sheep tibia: technical prerequisites
      and first results.
AB  - OBJECTIVE: The purpose of this study was to examine for the first time the
      feasibility of performing complete osteotomy of sheep tibia using a computer
      guided CO2-laser osteotome, and to examine bone healing under functional loading.
      BACKGROUND DATA: Bone cutting without aggravating thermal side effects has been
      demonstrated with scanning CO2-laser osteotomy. Further research is necessary to
      develop a clinically usable laser osteotome, which may allow new types of bone
      surgical procedures. MATERIALS AND METHODS: The scanning parameters for
      performing tibial osteotomies were determined in preliminary ex vivo trials.
      Osteotomies were performed in the mid-diaphysis of sheep tibia using either the
      prototype laser osteotome (osteoLAS, study group; n = 12), or an oscillating saw
      (control group; n = 12). Both groups were divided into two subgroups each (n =
      6), and the two groups were sacrificed after 4 and 12 wk. Radiographs were taken
      postoperatively and after 4, 8, and 12 wk to compare the course of bone healing.
      RESULTS: Laser osteotomies of sheep tibia up to a depth of 20 mm were possible
      without visible thermal damage to the bone. A sequential PC-controlled cut
      geometry with artificial widening of the osteotomy gap was required for a
      complete osteotomy. Both clinically and radiologically, the laser and control
      groups showed undisturbed primary gap healing. Bone healing was similar and
      undelayed after both laser osteotomy and osteotomy done by mechanical saw.
      CONCLUSIONS: Osteotomy of multi-layered bones with a scanning CO2-laser
      demonstrates clinical and radiological healing patterns comparable to those seen
      with osteotomy done by standard mechanical instruments. It is, however, a
      technically demanding procedure, and complete laser osteotomies of long bones are
      only reasonable in bones with a diameter <20 mm, which will likely restrict the
      use of this technique to bones 7-10 mm thick. Through the use of computer
      guidance, extremely precise osteotomies and sophisticated cut geometries are
      possible using this technique. For practical applications, precise control of the
      depth of laser cutting and easier manipulation of the osteotome are required.

PMID- 18341419
TI  - The combined treatment effects of therapeutic laser and exercise on tendon
      repair.
AB  - OBJECTIVE: In this study we investigated the effects of different intensities of
      therapeutic laser energy and running exercise, and their combined effects on the
      repair of Achilles tendons in rats. MATERIALS AND METHODS: Thirty-six mature
      Sprague-Dawley rats that received surgical hemi-transection of their right
      Achilles tendon were tested. Three laser dosages (4 J/cm2, 1 J/cm2 and 0 J/cm2)
      and three running periods (30 min, 15 min, and 0 min) resulting in nine different
      dosage and time groups were studied with four rats in each group. The treatments
      were given on alternate days starting on day 5 post-injury. On day 22, the
      tendons were tested for load-relaxation, stiffness, and ultimate strength.
      RESULTS: There was a significant effect of laser energy on normalized load
      relaxation, the rats receiving 4 J/cm2 had less load-relaxation than those
      receiving no laser treatment (p = 0.05). Results of stiffness testing revealed a
      significant effect, and rats that ran for 30 min had more stiffness than those
      that did not run (p = 0.015). For ultimate strength, due to a significant
      interaction (p = 0.05), the two factors were analyzed separately, and the results
      showed that for rats receiving no laser therapy, those that had run for 15 min
      and 30 min had more strength than those that did not run (p = 0.02 and 0.04,
      respectively). CONCLUSIONS: Both laser therapy and running were found to hasten
      Achilles tendon repair In general, the rats that received higher dosages of laser
      energy (4 J/cm2) and ran for longer periods (30 min) performed better than those
      that received lower dosages of laser energy and ran for shorter periods.

PMID- 18341420
TI  - Infrared laser light further improves bone healing when associated with bone
      morphogenetic proteins and guided bone regeneration: an in vivo study in a rodent
      model.
AB  - OBJECTIVE: This study assessed histologically the effect of laser
      photobiomodulation on the repair of surgical defects created in the femurs of
      Wistar rats treated or not treated with bone morphogenetic proteins (BMPs) and
      organic bovine bone graft. BACKGROUND DATA: This paper is part of an ongoing
      series of works in which biomaterials and/or guided bone regeneration (GBR) are
      used in association with laser photobiomodulation. Several previous reports from
      our group have shown that the use of laser photobiomodulation improves the
      treatment of bone defects. MATERIALS AND METHODS: Forty-eight adult male Wistar
      rats were divided into four randomized groups: group 1 (controls, n = 12); group
      2 (laser photobiomodulation, n = 12); group 3 (BMPs + organic bovine bone graft +
      GBR, n = 12); and group 4 (BMPs + organic bovine bone graft + GBR + laser
      photobiomodulation, n = 12). The irradiated groups received seven irradiations
      every 48 h, the first immediately after the surgical procedure. Laser
      photobiomodulation (830 nm, 40 mW, CW, phi approximately 0.6 mm) consisted of a
      total of 16 J/cm2 per session at four points (4 J/cm2 each) equally spaced around
      the periphery of the defect. The animals were sacrificed after 15, 21, and 30 d,
      and the specimens were routinely embedded in wax and stained with hematoxylin and
      eosin and Sirius red stains and analyzed under light microscopy. RESULTS: The
      results showed histological evidence of increased deposition of collagen fibers
      (at 15 and 21 d), as well as an increased amount of well-organized bone trabeculi
      at the end of the experimental period (30 d) in irradiated animals compared to
      non-irradiated controls. CONCLUSION: We concluded that the use of laser
      photobiomodulation in association with BMPs, organic bovine bone grafts, and GBR
      increases the positive biomodulating effects of laser energy.

PMID- 18341421
TI  - Treatment of hemangioma of the head and neck with diode laser and forced
      dehydration with induced photocoagulation.
AB  - OBJECTIVE: The aim of this study was to investigate the efficacy of treating oral
      hemangiomas using forced dehydration with induced photocoagulation (FDIP) via
      diode laser. METHODS: One-hundred sixty patients were treated between 1999 and
      2006 (76 men, 46%; 84 women, 54%). In 136 cases we used FDIP to treat hemangioma,
      and in 24 cases complete surgical excision was performed. One-hundred thirty-four
      lesions had a surface area <2 x 2 cm2, whereas only two had large lesions
      measuring 2.5 x 2 cm2. RESULTS: In 136 patients with hemangiomas treated with
      FDIP, 134 cases (98.53%) showed complete remission, one case (0.735%) did not
      show complete remission, and one case (0.735%) displayed tumor growth. There were
      no adverse effects and all patients were carefully followed-up until complete
      healing was documented, along with any complications. CONCLUSIONS: Our findings
      suggest that FDIP is a useful and effective treatment for benign oral vascular
      lesions. FDIP treatment of these oral lesions is clinically significant because
      it provides effective management, avoids recurrence, and shortens healing time.
      We believe that the use of this method by medical and dental specialists should
      be supported.

PMID- 18341422
TI  - Therapy of anemia in kidney failure, using plasmid encoding erythropoietin.
AB  - Numerous studies using erythropoietin (EPO) gene delivery vectors, either viral
      or nonviral, have shown uncontrolled EPO expression leading to transient or
      sustained erythrocytosis and, more recently, severe autoimmune anemia. Therefore,
      there is a need to develop other EPO gene delivery systems that allow sustained
      and adjustable expression of EPO. We have examined a new approach of delivering
      plasmid encoding mouse EPO cDNA into mouse skeletal muscle, using an amphiphilic
      block copolymer. Repeated injections of low doses of block copolymer-EPOcDNA
      formulations increased hematocrit in a dose-dependent manner for more than 9
      months, without any initial overshoot. Low doses of block copolymer-EPOcDNA
      formulations prevented autoimmune anemia in immunocompetent Swiss mice and
      prevented or reversed chronic anemia in an acquired mouse model of renal failure.
      We conclude that repeated injections of low doses of block copolymer-DNA
      formulations that do not induce (1) inflammation at the injection site, (2)
      overexpression of EPO, or (3) the production of anti-EPO neutralizing auto
      antibodies hold promise for in vivo expression of therapeutic proteins, in
      particular for systemic delivery.

PMID- 18341423
TI  - Immunological approaches for amyloid-beta clearance toward treatment for
      Alzheimer's disease.
AB  - The pathology of Alzheimer's disease is characterized primarily by extracellular
      plaques and intracellular neurofibrillary tangles. Plaques are composed mainly of
      the amyloid-beta peptide, whereas tangles are derived from the cytoskeletal
      protein tau. The most studied hypothesis of development of the disease is that of
      the amyloid cascade, which states that overproduction of amyloid-beta peptide, or
      failure to clear this peptide, leads to Alzheimer's disease primarily through
      amyloid deposition, which is presumed to be involved in neurofibrillary tangle
      formation; these lesions are then associated with cell death, which is reflected
      in memory impairment, the hallmarks of this dementia. We developed a new concept
      showing that site-directed antibodies against amyloid-beta peptide may modulate
      formation of amyloid filaments, which has become the theoretical basis of the
      immunological approach for treatment of Alzheimer's disease. The performance of
      anti-beta-amyloid antibodies in transgenic mouse models of Alzheimer's disease
      showed they are delivered to the central nervous system, clearing amyloid plaques
      and protecting the mice from learning and age-related memory deficits. Amyloid
      plaque clearance via specific anti-amyloid-beta peptide antibodies follows
      multiple mechanisms. As immunotherapy is at the crossroads of immunology and the
      nervous system, a deeper understanding of the amyloid-beta peptide clearance
      mechanism may lead to an optimized therapeutic approach to the treatment of
      Alzheimer's disease. Antibodies generated with the first-generation vaccine might
      not have the desired therapeutic properties to target the "correct" mechanism,
      however, new immunological approaches are now under consideration.

PMID- 18341424
TI  - Zinc in elderly people: effects of zinc supplementation on psychological
      dimensions in dependence of IL-6 -174 polymorphism: a Zincage study.
AB  - Zinc is relevant for psychological dimensions, which are altered in zinc
      deficiency, as in aging. Since zinc deficiency and the beneficial effect of zinc
      supplementation may be related to genotypes of IL-6 -174 polymorphism, the main
      goal was to examine psychological dimensions in relationship to plasma zinc and
      genetic background of IL-6 in healthy elderly subjects, recruited in Italy,
      Greece, and Poland, before and after zinc supplementation. On the basis of IL-6 
      174 polymorphism, significant restoration occurs for PSS, especially in Greece
      and Poland, less for MMSE and GDS, after zinc supplementation, suggesting zinc is
      important in reducing stress in elderly people.

PMID- 18341425
TI  - Repeat mild heat shock increases dermal fibroblast activity and collagen
      production.
AB  - Repeat mild heat shock (RMHS) has been shown to have anti-aging effects on
      cellular and biological processes within human dermal fibroblasts. We have
      investigated the potential of an abridged mild heat shock regime to impact upon
      the functional properties of human dermal fibroblasts derived from three donors
      (male, 12 years; female, 22 years; female, 65 years). For each donor mild heat
      shock increased the rate of contraction of fibroblast-containing collagen gels
      and increased the de novo synthesis of collagen. Thus, hormetic mechanisms are
      proposed to provide functional anti-aging benefits to skin cells.

PMID- 18341426
TI  - Modulation of genes involved in zinc homeostasis in old low-grade atherosclerotic
      patients under effects of HMG-CoA reductase inhibitors.
AB  - Taking into account the antioxidant properties of zinc, it is difficult to
      explain the beneficial effects of HMG-CoA reductase inhibitors in the context of
      a well-known decreased zinc status. Therefore, intracellular zinc homeostasis was
      studied in patients with low-grade carotid atherosclerosis under treatment with
      HMG-CoA reductase inhibitors using a custom microarray-based approach developed
      by pooling information across microarray studies. Experimental data unravel an
      active zinc signaling in PBMC from low-grade atherosclerotic patients under lipid
      reduction therapy, suggesting that monitoring intracellular zinc status could be
      a key factor for an optimal strategy and targeting a level of intervention.

PMID- 18341427
TI  - Genetic polymorphisms and human aging: association studies deliver.
AB  - Aging shows great heterogeneity between people, with a substantial part
      attributable to genetic differences. In a candidate gene study across three older
      populations, polymorphisms in the p16/p15 locus (INK4a/INK4b, CDKN2a/b) were
      associated with a substantial difference in levels of physical functioning.
      Recent large-scale genome wide association (GWA) studies for type 2 diabetes and
      myocardial infarction have also found major variants in this locus, confirming
      the p16/p15 region as a key aging site. Many other GWA findings are in novel
      pathways, providing new potential targets for interventions to slow aging.

PMID- 18341428
TI  - Cerebral amyloid-beta protein accumulation with aging in cotton-top tamarins: a
      model of early Alzheimer's disease?
AB  - Alzheimer's disease (AD) is the most common progressive form of dementia in the
      elderly. Two major neuropathological hallmarks of AD include cerebral deposition
      of amyloid-beta protein (Abeta) into plaques and blood vessels, and the presence
      of neurofibrillary tangles in brain. In addition, activated microglia and
      reactive astrocytes are often associated with plaques and tangles. Numerous other
      proteins are associated with plaques in human AD brain, including Apo E and
      ubiquitin. The amyloid precursor protein and its shorter fragment, Abeta, are
      homologous between humans and non-human primates. Cerebral Abeta deposition has
      been reported previously for rhesus monkeys, vervets, squirrel monkeys,
      marmosets, lemurs, cynomologous monkeys, chimpanzees, and orangutans. Here we
      report, for the first time, age-related neuropathological changes in cotton-top
      tamarins (CTT, Saguinus oedipus), an endangered non-human primate native to the
      rainforests of Colombia and Costa Rica. Typical lifespan is 13-14 years of age in
      the wild and 15-20+ years in captivity. We performed detailed immunohistochemical
      analyses of Abeta deposition and associated pathogenesis in archived brain
      sections from 36 tamarins ranging in age from 6-21 years. Abeta plaque deposition
      was observed in 16 of the 20 oldest tamarins (>12 years). Plaques contained
      mainly Abeta42, and in the oldest animals, were associated with reactive
      astrocytes, activated microglia, Apo E, and ubiquitin-positive dystrophic
      neurites, similar to human plaques. Vascular Abeta was detected in 14 of the 20
      aged tamarins; Abeta42 preceded Abeta40 deposition. Phospho-tau labeled
      dystrophic neurites and tangles, typically present in human AD, were absent in
      the tamarins. In conclusion, tamarins may represent a model of early AD
      pathology.

PMID- 18341429
TI  - Aggregation and amyloid fibril formation of the prion protein is accelerated in
      the presence of glycogen.
AB  - Prion diseases like Creutzfeldt-Jakob disease in humans or scrapie in sheep and
      goats are infectious neurodegenerative diseases. Their infectious agent, called
      prion, is composed mainly of aggregated and misfolded prion protein and non
      proteinaceous components. An example of such a common non-proteinaceous secondary
      component of natural prions is the polysaccharide scaffold. We studied the
      influence of such a polysaccharide on the conformational transition of PrP
      applying an in vitro conversion system. Here we report that glycogen supports and
      accelerates PrP amorphous aggregation similar to seeded aggregation and leads to
      co-aggregates. Furthermore, PrP fibril formation was highly accelerated in the
      presence of glycogen.

PMID- 18341430
TI  - Quercetin attenuates UV- and H(2)O(2)-induced decrease of collagen type I in
      cultured human lens epithelial cells.
AB  - Ultraviolet (UV) radiation is related to cataract formation. The dynamics of
      matrix proteins play crucial roles in cell proliferation, cell migration, and the
      remodeling of lens capsule and, possibly, cataract formation. However, the change
      of dynamics of matrix proteins, such as collagens, in lens cells in response to
      UV radiation has not been investigated. Using cultured human lens epithelial
      cells, we, for the first time, demonstrate that UV radiation induces a decrease
      of collagen type I in a time- and dose-dependent manner. Hydrogen peroxide
      (H(2)O(2)) also induces a collagen type I decrease in a similar pattern. We
      observed that UV and H(2)O(2) induce JNK and its downstream component, c-Jun,
      activation in both a time- and dose-dependent manner. The pharmacologic inhibitor
      of JNK or JNKi inhibits UV-induced JNK and c-Jun activation and attenuates a UV
      induced decrease of collagen type I. Quercetin, a well known antioxidant, also
      protects against a UV- and H(2)O(2)-induced decrease of collagen type I in a dose
      dependent manner. Quercetin inhibits UV- and H(2)O(2)-induced JNK and c-Jun
      activation. Collectively, we conclude that quercetin attenuates both a UV- and
      H(2)O(2)-induced decrease of collagen type I via the inhibiting of JNK/c-Jun
      activity. Understanding the cellular-signaling pathways involved in the UV- and
      H(2)O(2)-induced decrease of collagen type I may reveal potential therapeutic
      targets for the UV-induced cataract.

PMID- 18341431
TI  - Effects of switching from topical beta-blockers to latanoprost on intraocular
      pressure in patients with normal-tension glaucoma.
AB  - AIMS: The effects of switching from topical beta-blockers (beta) to latanoprost
      (LA) on intraocular pressure (IOP) and IOP-reduction rate (IOP-RR) in patients
      with normal-tension glaucoma (NTG) were investigated. SUBJECTS AND METHODS: Sixty
      (60) NTG patients (60 eyes) were divided into three equal groups receiving
      carteolol hydrochloride (group A), nipradilol (group B), and betaxolol
      hydrochloride (group C) twice-daily for 3 months. The drugs were changed to
      topical LA administered once-daily for the next 3 months. RESULTS: Baseline IOP
      was 14.4 +/- 0.9, 14.6 +/- 0.6, and 14.6 +/- 0.9 mmHg in groups A, B, and C,
      respectively. At 3 months, IOP was 12.4 +/- 0.6, 13.4 +/- 0.6, and 12.9 +/- 0.8
      mmHg and 10.5 +/- 0.5, 11.1 +/- 0.8, and 11.7 +/- 0.8 mmHg at 6 months in groups
      A, B, and C, respectively. At 3 months, IOP-RR was 10.4 +/- 5.5, 9.5 +/- 2.6, and
      10.8 +/- 4.7% and 24.1 +/- 4.3, 22.9 +/- 5.9, and 19.4 +/- 3.8% at 6 months in
      groups A, B, and C, respectively. The groups did not significantly differ in the
      first 3 months regarding IOP and IOP-RR. Switching to LA significantly decreased
      IOP and increased IOP-RR in all groups. CONCLUSION: In NTG patients, LA reduced
      IOP more effectively than the beta tested.

PMID- 18341432
TI  - Insurance planning can be key in practice protection. Appropriate coverage can
      protect a veterinarian's future.

PMID- 18341433
TI  - Preparedness: global in nature, local in practice.

PMID- 18341434
TI  - Creationist questions JAVMA News statement.

PMID- 18341435
TI  - What is your diagnosis? Diagnosis: Luxation of the left patella with DJD
      involving the left stifle joint and subluxation of the left hip joint.

PMID- 18341436
TI  - Theriogenology question of the month. Cause of postestral vulvar discharge.

PMID- 18341437
TI  - Animal behavior case of the month. Persistent vomiting of food and gastric fluid
      about 3 times a day for the previous 24 months.

PMID- 18341438
TI  - Direct and indirect zoonotic transmission of Shiga toxin-producing Escherichia
      coli.

PMID- 18341439
TI  - Highlights juxtaposition of obesity article and dessert recipe.

PMID- 18341442
TI  - Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected
      idiopathic epilepsy.
AB  - OBJECTIVE: To assess pharmacokinetics, efficacy, and tolerability of oral
      levetiracetam administered as an adjunct to phenobarbital treatment in cats with
      poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label,
      noncomparative clinical trial. ANIMALS: 12 cats suspected to have idiopathic
      epilepsy that was poorly controlled with phenobarbital or that had unacceptable
      adverse effects when treated with phenobarbital. PROCEDURES: Cats were treated
      with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week
      of treatment, serum levetiracetam concentrations were measured before and 2, 4,
      and 6 hours after drug administration, and maximum and minimum serum
      concentrations and elimination half-life were calculated. Seizure frequencies
      before and after initiation of levetiracetam treatment were compared, and adverse
      effects were recorded. RESULTS: Median maximum serum levetiracetam concentration
      was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3
      microg/mL, and median elimination half-life was 2.9 hours. Median seizure
      frequency prior to treatment with levetiracetam (2.1 seizures/mo) was
      significantly higher than median seizure frequency after initiation of
      levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as
      having responded to levetiracetam treatment (ie, reduction in seizure frequency
      of >or=50%). Two cats had transient lethargy and inappetence. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that levetiracetam is well tolerated in
      cats and may be useful as an adjunct to phenobarbital treatment in cats with
      idiopathic epilepsy.

PMID- 18341444
TI  - Effects of training and strenuous exercise on hematologic values and peripheral
      blood leukocyte subsets in racing sled dogs.
AB  - OBJECTIVE: To determine the effects of training and sustained submaximal exercise
      on hematologic values in racing sled dogs. DESIGN: Cohort study. ANIMALS: 39
      Alaskan sled dogs bred for endurance racing. Procedures-Blood samples were
      collected prior to initiation of a 7-month training regimen (n=39), after
      completion of the training regimen (19), and after completion of an 1,100-mile
      race (9), and a CBC, differential cell count, and flow cytometry for leukocyte
      surface antigens were performed. RESULTS: Both training and exercise caused
      significant decreases in PCV and hemoglobin concentration and significant
      increases in total WBC count. In contrast, training and exercise were not found
      to have significant effects on absolute numbers or fractions of CD4+ or CD8+
      lymphocytes, other than a significant increase in the fraction of CD8+
      lymphocytes associated with training. CONCLUSIONS AND CLINICAL RELEVANCE: Results
      suggested that training and exercise induced changes in several hematologic
      values in racing sled dogs. Extracellular fluid volume expansion was the likely
      explanation for the training-induced decrease in PCV, and acute blood loss
      secondary to gastrointestinal tract bleeding was likely responsible for the
      decrease in PCV associated with acute exercise.

PMID- 18341445
TI  - Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short
      term single-agent protocol in dogs with lymphoma.
AB  - OBJECTIVE: To compare response rates and remission and survival times in dogs
      with lymphoma treated with a continuous, multiagent, doxorubicin-based
      chemotherapeutic protocol or with a short-term single-agent protocol
      incorporating doxorubicin. DESIGN: Nonrandomized controlled clinical trial.
      ANIMALS: 114 dogs with lymphoma. PROCEDURES: Dogs were treated with a
      chemotherapeutic protocol consisting of L-asparaginase, vincristine,
      cyclophosphamide, doxorubicin, methotrexate, and prednisolone (n=87) or
      doxorubicin alone (27). RESULTS: 63 of 86 (73%) dogs treated with the multiagent
      protocol (data on response was unavailable for 1 dog) and 14 of 27 (52%) dogs
      treated with the single-agent protocol had a complete remission. Dogs with
      lymphoma classified as substage<or=and dogs with a high BUN concentration at the
      time of initial diagnosis were significantly less likely to have a complete
      remission. No significant difference in remission or survival time could be
      demonstrated between treatment groups. Incidence of hematologic and
      gastrointestinal tract toxicoses did not differ between treatment groups, with
      the exception that vomiting was more common among dogs treated with the
      multiagent protocol. CONCLUSIONS AND CLINICAL RELEVANCE: In this population of
      dogs, we were not able to identify any significant difference in remission or
      survival times between dogs with lymphoma treated with a continuous, multiagent
      chemotherapeutic protocol and dogs treated with a short-term single-agent
      protocol involving doxorubicin.

PMID- 18341446
TI  - Arthropathy caused by a lead bullet in a dog.
AB  - CASE DESCRIPTION: A 3-year-old spayed female Labrador Retriever was evaluated for
      progressive lameness of the left forelimb 21 months after being shot in the elbow
      with a lead bullet. CLINICAL FINDINGS: Physical examination findings were
      consistent with moderate osteoarthritis of the left elbow joint. Orthogonal
      radiographic views of the elbow revealed multiple metallic fragments in and
      around the joint space as well as signs of osteoarthritis. TREATMENT AND OUTCOME:
      The elbow joint was evaluated arthroscopically. A lead-based bullet fragment was
      seen in the lateral synovial compartment and removed in multiple pieces. Excess
      fibrin and synovium were removed, and microfractures were created in exposed
      subchondral bone to stimulate neovascularization and fibrocartilage formation. In
      a follow-up telephone conversation 4 months after surgery, the owner reported a
      marked improvement in the lameness. CLINICAL RELEVANCE: Removal of lead intra
      articular foreign bodies may be indicated even if the material is not believed to
      mechanically interfere with joint motion.

PMID- 18341447
TI  - Comparison of tibial plateau angles in dogs with unilateral versus bilateral
      cranial cruciate ligament rupture: 150 cases (2000-2006).
AB  - OBJECTIVE: To compare tibial plateau angle (TPA) in dogs with unilateral versus
      bilateral cranial cruciate ligament (CCL) rupture, to compare right versus left
      TPA in dogs with bilateral CCL rupture, and to determine whether TPA can be used
      to predict whether a dog with unilateral CCL rupture would subsequently rupture
      the contralateral CCL. DESIGN: Retrospective case series. ANIMALS: 150 dogs with
      unilateral (n=58) or bilateral (92) CCL rupture. PROCEDURES: Medical records were
      reviewed and TPA was recorded. Dogs with unilateral CCL rupture that were not
      known to have ruptured the contralateral ligament were followed up for a minimum
      of 2 years. RESULTS: Dogs with unilateral CCL rupture were significantly older
      (median, 7.0 years) than dogs with bilateral CCL rupture (median, 4.5 years).
      Median TPA for dogs with unilateral CCL rupture (26 degrees) was not
      significantly different from median TPA for dogs with bilateral rupture (27
      degrees in both the right and left limbs), and right and left TPAs were not
      significantly different in dogs with bilateral CCL rupture. There was no
      correlation between TPA and the time interval between diagnosis of the initial
      and subsequent CCL ruptures in dogs with bilateral CCL rupture. CONCLUSION AND
      CLINICAL RELEVANCE: Results suggested that TPA in the range studied (mostly<35
      degrees) was not a useful predictor of contralateral CCL rupture among dogs with
      unilateral CCL rupture, although age may be a risk factor for development of
      bilateral CCL rupture. The incidence of bilateral CCL rupture may be higher than
      previously reported.

PMID- 18341448
TI  - Relationship between Doppler blood pressure and survival or response to treatment
      in critically ill cats: 83 cases (2003-2004).
AB  - OBJECTIVE: To evaluate the relationship between Doppler blood pressure (DBP) and
      survival or response to treatment in critically ill cats. DESIGN: Retrospective
      case series. ANIMALS: 83 cats. PROCEDURES: Medical records from cats admitted to
      the intensive care unit with at least 2 recorded DBP measurements were included
      in the study. Hypotension was defined as 1 or more DBP measurements d 90 mm Hg.
      Change in blood pressure, survival to hospital discharge, heart rate, rectal
      temperature, PCV, plasma pH, serum ionized calcium concentration, disease
      process, body weight, age, duration of hospitalization, and catecholamine
      treatment were also evaluated. RESULTS: 39 cats were included in the hypotensive
      group, and 44 were consistently normotensive. Overall survival rate was 53%
      (44/83), with a significantly higher mortality rate in the hypotensive group (64%
      vs 32%). Among other variables, only low rectal temperature and low PCV were
      significantly associated with hypotension. Hypotensive cats with an increase in
      blood pressure of >or=20 mm Hg during hospitalization were more likely to survive
      to discharge (mortality rate, 69% vs 17%). CONCLUSIONS AND CLINICAL RELEVANCE:
      Hypotensive cats had increased mortality rate with lower rectal temperatures and
      lower PCV, compared with normotensive critically ill cats. The implications of
      these findings with regard to treatment remain to be elucidated, but addressing
      these abnormalities may be appropriate.

PMID- 18341449
TI  - Multinodular pulmonary fibrosis in five horses.
AB  - CASE DESCRIPTION: 5 horses were evaluated because of decreased appetite, weight
      loss, fever, cough, tachypnea, and respiratory distress. CLINICAL FINDINGS:
      Tachycardia, tachypnea, increased respiratory effort, lethargy, fever, poor body
      condition, and nasal discharge were detected in various combinations on initial
      physical examination. Evaluation of the lower portion of the respiratory tract
      via radiography and ultrasonography revealed a severe nodular interstitial
      pattern. Histologic examination of lung tissue revealed interstitial expansion of
      alveolar parenchyma with collagen, intraluminal accumulation of neutrophils and
      macrophages within the alveoli, and occasional intranuclear inclusion bodies
      within alveolar macrophages. Equine herpesvirus type 5 was detected in samples of
      lung tissue, bronchoalveolar lavage fluid, or both via polymerase chain reaction
      assay in all cases. A diagnosis of equine multinodular pulmonary fibrosis (EMPF)
      was established. TREATMENT AND OUTCOME: Horses were provided supportive treatment
      and were administered a variety of medications including corticosteroids and
      acyclovir. Two horses survived and returned to their previous level of activity.
      Three horses were euthanized because of either deterioration of clinical
      condition (n=2) or failure to improve within 4 weeks of initiation of treatment
      (1). CLINICAL RELEVANCE: EMPF should be considered as a differential diagnosis
      for adult horses with interstitial pneumonia and should be suspected on the basis
      of characteristic radiographic, ultrasonographic, and histopathologic findings.
      Equine herpesvirus type 5 is found in association with EMPF; although the exact
      pathogenic role this virus plays in EMPF is unknown, equine herpesvirus type 5
      may be an etiologic agent or cofactor in the development of EMPF.

PMID- 18341450
TI  - A field evaluation of mortality rate and growth performance in pigs vaccinated
      against porcine circovirus type 2.
AB  - OBJECTIVE: To evaluate, under field conditions, the effects of a commercial
      porcine circovirus type 2 (PCV2) vaccine on mortality rate and growth performance
      in a herd infected with PCV2 that had a history of porcine circovirus disease.
      DESIGN: Randomized controlled clinical trial. ANIMALS: 485 commercial, cross
      bred, growing pigs. PROCEDURES: Prior to weaning, pigs were randomly assigned
      within litter to a vaccination or unvaccinated control group. Pigs in the
      vaccination group were given a commercial PCV2 vaccine at weaning and 3 weeks
      later. Mortality rate was recorded, and pigs were weighed prior to vaccination,
      when moved from the nursery, and prior to marketing. Infection status was
      assessed by serologic testing and detection of viral DNA in serum. RESULTS:
      Compared with control pigs, pigs vaccinated against PCV2 had a significantly
      lower mortality rate during the finishing phase, significantly higher average
      daily gain during the finishing phase, and significantly lower likelihood of
      being lightweight at the time of marketing. For vaccinated pigs, overall
      mortality rate was reduced by 50% and average daily gain during the finishing
      period was increased by 9.3%. At the time of marketing, vaccinated pigs weighed
      an average of 8.8 kg (19.4 lb) more than control pigs, without any difference in
      days to marketing. Serum PCV2 antibody titers increased in control pigs, and PCV2
      DNA was detected, indicating active PCV2 infection. CONCLUSIONS AND CLINICAL
      RELEVANCE: Results suggested that vaccination against PCV2 was effective at
      reducing mortality rate and improving growth performance among pigs in a herd
      infected with PCV2.

PMID- 18341451
TI  - Selecting medical students.

PMID- 18341452
TI  - Obstructive sleep apnoea--getting to the heart of the matter?

PMID- 18341454
TI  - Booster seat use by children aged 4-11 years: evidence of the need to revise
      current Australasian standards to accommodate overweight children.
AB  - OBJECTIVE: To examine the relationship between child weight and vehicle booster
      seat usage in the context of current Australasian booster seat standards. DESIGN,
      SETTING AND PARTICIPANTS: Questionnaire survey conducted between February and
      April 2005. A convenience sample of parents with children aged 4-11 years in New
      South Wales and Victoria completed a questionnaire, reporting on the height and
      weight of their children and the nature of restraint devices used in the family
      vehicle. MAIN OUTCOME MEASURES: Proportion of children meeting standard-specified
      weight and height criteria who are not restrained in booster seats; proportion of
      children who meet the specified height criteria but whose weight exceeds the
      specified weight. RESULTS: 699 of 3959 questionnaires were returned (response
      rate, 18%), of which seven lacked essential details. The remaining 692 responses
      provided information on 1500 children. Of these children, 633 aged 4-11 years
      fell within the recommended height range for using booster seats, but only 29%
      were typically restrained in booster seats, the majority (70%) being restrained
      in normal seatbelts. A key finding was that 37% of the children who met the
      recommended height criteria exceeded the maximum weight for booster seats
      stipulated by the current Australasian safety standard. CONCLUSION: In view of
      increasing rates of overweight and obesity in children, it is important to
      reassess current Australasian standards for child restraints in vehicles. A
      concerted parental education campaign is also needed to raise awareness of which
      restraint types are appropriate for children of various heights and weights.

PMID- 18341455
TI  - Comparing risk-prediction methods using administrative or clinical data in
      assessing excess in-hospital mortality in patients with acute myocardial
      infarction.
AB  - OBJECTIVES: To compare results of statistical process-control analyses of in
      hospital deaths of patients with acute myocardial infarction by using either
      administrative or clinical data sources and prediction models, and to assess
      variation in results according to selected patient characteristics. DESIGN:
      Retrospective, cross-sectional study comparing variable life-adjusted display
      (VLAD) curves derived by using administrative or clinical prediction models
      applied to a single patient sample. PARTICIPANTS AND SETTING: Data from 467
      consecutive patients admitted to a tertiary hospital in Queensland, between 1
      July 2003 and 31 March 2006, with a coded discharge diagnosis of acute myocardial
      infarction. MAIN OUTCOME MEASURE: Statistical estimates of cumulative lives
      gained or lost in excess of those predicted at the end of the study period.
      RESULTS: The two prediction models, when applied to all patients, generated
      almost identical VLAD curves, showing a steadily increasing excess mortality over
      the study period, culminating in an estimated 11 excess deaths. Risk estimates
      for individual patients from each model were significantly correlated (r = 0.46,
      P < 0.001). After exclusion of misclassified cases, out-of-hospital cardiac
      arrests and deaths within 30 minutes of presentation, replotting the curves
      reversed the mortality trend and yielded, depending on the model, a net gain of
      three or seven lives. After further exclusion of transfers in from other
      hospitals and patients whose care had a palliative or conservative intent, the
      net gain increased to seven or 10 lives. CONCLUSION: Appropriate patient
      selection is more important than choice of dataset or risk-prediction model when
      statistical process-control methods are used to flag unfavourable mortality
      trends suggestive of suboptimal hospital care.

PMID- 18341456
TI  - Prescribing of psychostimulant medications for attention deficit hyperactivity
      disorder in children: differences between clinical specialties.
AB  - OBJECTIVE: To examine differences in psychostimulant prescribing between
      paediatricians and child/adolescent psychiatrists for treating children with
      attention deficit hyperactivity disorder (ADHD) in Western Australia. DESIGN:
      Using whole-population prescribing data, logistic and linear regressions were
      used to model the number of children (aged 2-17 years) treated with
      psychostimulants between August 2003 and December 2004 for ADHD and medication
      dose prescribed by clinical specialty, controlling for age, sex, body weight, and
      other medication use. MAIN OUTCOME MEASURES: Mean number of patients treated by
      specialty; associations between prescriber specialty and patient characteristics;
      associations between stimulant dose and patient characteristics and prescriber
      specialty. RESULTS: 54 paediatricians and 23 child/adolescent psychiatrists
      prescribed stimulant medications for children with ADHD. The mean number of
      patients treated (per prescriber) was 159.8 (range, 1-1977) for paediatricians
      and 34.3 (range, 1-166) for psychiatrists. Boys were 32% more likely to be
      treated with stimulants by paediatricians (P = 0.002). Psychiatrists were 2.9
      times (95% CI, 2.4-3.3; P < 0.001) more likely than paediatricians to treat
      patients with multiple psychotropic medications. When controlled for all other
      factors, psychiatrists prescribed higher stimulant doses (4.5 mg/day greater; 95%
      CI, 2.0-7.0 mg/day; P < 0.001) than paediatricians. CONCLUSION: Treatment of
      children with stimulant medicines for ADHD differed between clinical specialties.
      Paediatricians treated more patients per prescriber, a greater proportion of
      boys, and a younger age demographic, but relied less on combined psychotropic
      pharmacotherapy and prescribed lower stimulant doses than psychiatrists.

PMID- 18341457
TI  - Outcomes for general medical inpatients with diabetes mellitus and new
      hyperglycaemia.
AB  - OBJECTIVES: To investigate the relationship between admission glycaemic status
      and inpatient mortality in patients with and without pre-existing diabetes.
      DESIGN: Prospective observational cohort study. SETTING: A general medical ward
      in an Australian tertiary referral hospital. PARTICIPANTS: 903 patients admitted
      to the general medical ward between February 2003 and July 2004. MAIN OUTCOME
      MEASURE: Inpatient death. RESULTS: The overall inpatient mortality was 5.4% (n =
      49). In the total cohort, age > 75 years and admission fasting plasma glucose
      (FPG) levels > or = 5.6 mmol/L were independent predictors of mortality. For
      patients without a known history of diabetes, each 1 mmol/L rise in admission FPG
      was associated with a 33% increase in mortality. In these patients, elevated (>
      6.0%) and normal glycated haemoglobin (HbA(1c)) levels were associated with
      mortalities of 11.3% and 4.4%, respectively (odds ratio, 2.47; 95% CI, 1.16
      5.26). In contrast, in patients with known diabetes, there was no association
      between admission FPG levels, HbA(1c) and mortality. Length of stay was not
      independently associated with FPG, HbA(1c), or diabetes status. CONCLUSIONS: In
      patients without known diabetes, the risk of death was increased for admission
      FPG levels > or = 5.6 mmol/L. However, pre-existing abnormal glucose metabolism,
      reflected by elevated HbA(1c) levels, appeared a more important predictor of
      inpatient mortality than glucose levels in patients without known diabetes.

PMID- 18341458
TI  - Community-based asylum seekers' use of primary health care services in Melbourne.
AB  - OBJECTIVE: To investigate primary health care service utilisation and health
      presentations among asylum seekers living in Melbourne. DESIGN AND SETTING:
      Retrospective audit of files of people who attended three Melbourne asylum-seeker
      health clinics between 1 July 2005 and 30 June 2006. MAIN OUTCOME MEASURES: Rates
      of reasons for the encounter, diagnostic tests or investigations required,
      treatments prescribed and referrals. RESULTS: Data were collected from 998
      consultations corresponding to 341 people. Eighty-eight per cent of visits
      involved people with no Medicare access, owing to their visa status. The most
      common reasons for the encounter were general and unspecified symptoms or
      problems (rate, 59.9 per 100 encounters; 95% CI, 55-65), followed by
      musculoskeletal conditions (27.1; 95% CI, 24-30), and psychological problems
      (26.5; 95% CI, 23-30). The rate of referrals was 18.3 per 100 encounters (95% CI,
      16-21). CONCLUSIONS: The three clinics providing services to asylum seekers in
      Melbourne are delivering care to a considerable number of people with complex
      health needs. A substantial number of asylum seekers present to clinics with
      psychological and social problems. Most cannot access government-subsidised
      health care. This must be addressed urgently by policy change at the federal and
      state and territory levels.

PMID- 18341459
TI  - Medical school selection criteria and the prediction of academic performance.
AB  - OBJECTIVE: To assess how well prior academic performance, admission tests, and
      interviews predict academic performance in a graduate medical school. DESIGN,
      SETTING AND PARTICIPANTS: Analysis of academic performance of 706 students in
      three consecutive cohorts of the 4-year graduate-entry medical program at the
      University of Queensland. MAIN OUTCOME MEASURES: Proportion of academic
      performance during the medical program explained by selection criteria, and
      correlation between selection criteria and performance. Selection criteria were
      grade point average (GPA), GAMSAT (Graduate Australian Medical School Admissions
      Test) score, and interview score. Academic performance was defined as overall
      total in all examinations combined, in first and fourth year examinations, and in
      individual written, ethics and clinical components. RESULTS: Selection criteria
      explained 21.9% of variation in overall total score, falling from 28.2% in Year 1
      to 17.7% in Year 4. This was highest for the written examination in Year 1
      (30.5%) and lowest for the clinical examination in Year 4 (10.9%). GPA was most
      strongly correlated with academic performance (eg, for overall score, partial
      Spearman's correlation coefficient [pSCC], 0.47; P < 0.001), followed by
      interviews (pSCC, 0.12; P = 0.004) and GAMSAT (pSCC, 0.07; P = 0.08). The
      association between GPA and performance waned from Year 1 to Year 4, while the
      association between interview score and performance increased from Year 1 to Year
      4. CONCLUSION: The school's selection criteria only modestly predict academic
      performance. GPA is most strongly associated with performance, followed by
      interview score and GAMSAT score. The school has changed its selection process as
      a result.

PMID- 18341460
TI  - Effectiveness of complementary and self-help treatments for anxiety in children
      and adolescents.
AB  - OBJECTIVE: To review the evidence for the effectiveness of complementary and self
      help treatments for anxiety disorders and situational anxiety in children and
      adolescents. DATA SOURCES: Systematic literature search using PubMed, PsycINFO
      and the Cochrane Library for 111 treatments up to February 2006. STUDY SELECTION:
      There were 11 treatments for which intervention studies had been undertaken and
      reported. DATA EXTRACTION: Studies on each treatment were reviewed by one author
      and checked by a second. A consensus was reached for level of evidence. DATA
      SYNTHESIS: Relevant evidence was available for bibliotherapy, dance and movement
      therapy, distraction techniques, humour, massage, melatonin, relaxation training,
      autogenic training, avoiding marijuana, a mineral-vitamin supplement (EMPower +)
      and music therapy. Findings from case-control studies, individual cohort studies
      or low quality randomised controlled trials indicated that several treatments may
      have potential to reduce anxiety, including bibliotherapy, massage, melatonin,
      and relaxation training. CONCLUSIONS: Although some complementary and self-help
      treatments might be useful for children and adolescents with anxiety, they need
      to be tested adequately through randomised controlled trials before they could be
      recommended.

PMID- 18341461
TI  - Consent in paediatric research: an evaluation of the guidance provided in the
      2007 NHMRC National statement on ethical conduct in human research.
AB  - In 2007, the National Health and Medical Research Council (NHMRC) released a
      revised National statement on ethical conduct in human research. Public
      submissions in the review process leading to the 2007 statement highlighted four
      main areas of concern: children's competence to consent, mature minors and the
      requirement for parental consent, whether children can refuse to participate, and
      the provision of information to children. A useful addition to the statement is
      the concept of levels of maturity, which help determine whether a child or young
      person's consent is necessary and/or sufficient for participation in research.
      Changes in terminology ("capacity" instead of "competence" and introduction of
      the term "vulnerability") have the potential to create confusion, as the new
      terms are not clearly defined, and capacity is used in several senses.

PMID- 18341462
TI  - Preventing primary liver cancer: how well are we faring towards a national
      hepatitis B strategy?
AB  - Worldwide, over 80% of primary liver cancers are attributable to chronic
      infection with hepatitis B or C virus. Over the past two decades, primary liver
      cancer incidence rates have been consistently rising in Australia. In New South
      Wales, the standardised incidence ratios for primary liver cancer in males born
      in Vietnam, Hong Kong and Macau, Korea, Indonesia and China and in females born
      in Vietnam and China are 6-12 times those in Australian-born populations. The
      incidence of liver cancer is likely to continue to increase unless a coordinated
      approach to disease control can be developed. Effective programs for chronic
      hepatitis B management need to link prevention, treatment and care, and enhance
      opportunities for research and surveillance activities. The evidence that
      suppression of hepatitis B virus replication could limit disease progression
      needs to inform the development of a public health response. Lessons learned in
      the development of the National Hepatitis C Strategy and the experience of
      international hepatitis B control programs need to inform this process.

PMID- 18341463
TI  - Safe year-long use of a very-low-calorie diet for the treatment of severe
      obesity.
AB  - We report the case of a 59-year-old severely obese man with coexisting type 2
      diabetes, hypertension and dyslipidaemia who was treated with a very-low-calorie
      diet (VLCD) program for 12 months. He continued to lose weight during the
      treatment, with marked improvement in his comorbidities and no adverse effects.
      This case demonstrates that prolonged use of a VLCD under close medical
      supervision is safe and effective in certain obese patients.

PMID- 18341464
TI  - Acute unilateral anterior uveitis and scleritis following a single infusion of
      zoledronate for metastatic breast cancer.

PMID- 18341465
TI  - NHMRC grant applications: a comparison of "track record" scores allocated by
      grant assessors with bibliometric analysis of publications.

PMID- 18341466
TI  - Necrotising pneumonia due to Panton-Valentine leukocidin-positive methicillin
      sensitive Staphylococcus aureus.

PMID- 18341467
TI  - Tako-tsubo cardiomyopathy: how stress can mimic acute coronary occlusion.

PMID- 18341469
TI  - Our hearts and minds--what would it take to become the healthiest country in the
      world?

PMID- 18341470
TI  - Patient journeys: the process of clinical redesign.
AB  - *Clinical process redesign is a successful improvement method that has been used
      to increase access to health services in 60 public hospitals across New South
      Wales, and at Flinders Medical Centre (FMC) in South Australia. *The method
      focuses on the patient journey as the primary improvement locus, and uses process
      mapping to identify the value-adding steps in that journey; it involves redesign
      teams identifying and eliminating non-value-adding steps to improve flow and
      reduce delays in access to emergency and elective care. *The method engages
      clinicians, managers, patients and carers, and delivers real gains in health care
      delivery. *This article outlines the clinical process redesign programs being
      used by NSW Health and at FMC.

PMID- 18341471
TI  - Clinical process redesign for unplanned arrivals in hospitals.
AB  - *Emergency department performance had been deteriorating in NSW Health facilities
      and at Flinders Medical Centre before a fundamentally new approach involving a
      redesign method, additional bed capacity and more rigorous hospital performance
      management was applied. *Redesign was undertaken in over 60 hospitals in New
      South Wales. *Numerous disconnections and misalignments in the process of care
      delivery have been uncovered during the diagnostic phase of this redesign.
      *Solutions addressed the entire patient journey through the hospital, to produce
      smoother patient flow along the continuum of care. *To achieve a sustained
      improvement in performance, numerous solutions must be simultaneously implemented
      in each hospital. *With this multipronged approach, a turnaround in NSW emergency
      access performance has been achieved in the face of rising demand for services;
      the improvement has continued over 3 years. *This article reports on our findings
      from system-wide redesign for unplanned hospital attendances.

PMID- 18341472
TI  - Applying clinical process redesign methods to planned arrivals in New South Wales
      hospitals.
AB  - *Competing demands of planned and unplanned arrivals present major challenges for
      hospitals. *Applying clinical process redesign methods to the planned patient
      journey allows management to recognise the blocks and inefficiencies in the
      journey and facilitates the development of solutions for improvement. *Redesign
      of the planned patient journey in New South Wales has promoted the expansion of
      the extended day-only model of care, reformed the waiting times policy,
      standardised patient preadmission assessment and preparation, and targeted
      operating theatre use. *Improved performance management at Area Health Service
      and local facility levels has accompanied the redesign of planned arrival
      processes. *The results in redesign of surgery undertaken by the Area Health
      Services in 96 NSW hospitals have been impressive, with results within 2 years of
      commencing the clinical services redesign program showing: a 97% reduction in the
      numbers of patients in Category 1 (admission desirable within 30 days) whose
      surgery was overdue, from 5308 in January 2005 to 135 in June 2007; and a 99%
      reduction in the number of patients who have waited > 365 days for surgery, from
      10 551 in January 2005 to 84 in June 2007. *Improved surgical service efficiency,
      safety and quality justify the continuation of the redesign program.

PMID- 18341473
TI  - Redesigning care at the Flinders Medical Centre: clinical process redesign using
      "lean thinking".
AB  - *The Flinders Medical Centre (FMC) Redesigning Care program began in November
      2003; it is a hospital-wide process improvement program applying an approach
      called "lean thinking" (developed in the manufacturing sector) to health care.
      *To date, the FMC has involved hundreds of staff from all areas of the hospital
      in a wide variety of process redesign activities. *The initial focus of the
      program was on improving the flow of patients through the emergency department,
      but the program quickly spread to involve the redesign of managing medical and
      surgical patients throughout the hospital, and to improving major support
      services. *The program has fallen into three main phases, each of which is
      described in this article: "getting the knowledge"; "stabilising high-volume
      flows"; and "standardising and sustaining". *Results to date show that the
      Redesigning Care program has enabled the hospital to provide safer and more
      accessible care during a period of growth in demand.

PMID- 18341474
TI  - Implementing and sustaining transformational change in health care: lessons
      learnt about clinical process redesign.
AB  - *Clinical process redesign has enabled significant improvements in the delivery
      of health care services in emergency departments and elective surgery programs in
      New South Wales and at Flinders Medical Centre in South Australia, with tangible
      benefits for patients and staff. *The principles used in clinical process
      redesign are not new; they have been applied in other industries with significant
      gains for many years, but have only recently been introduced into health care
      systems. *Through experience with clinical process redesign, we have learnt much
      about the factors critical to the success of implementing and sustaining this
      process in the health care setting. *The key elements for success are leadership
      by senior executives, clinical leadership, team-based problem solving, a focus on
      the patient journey, access to data, ambitious targets, strong performance
      management, and a process for maintaining improvement.

PMID- 18341475
TI  - Clinical process redesign--can the leopard change its spots?

PMID- 18341476
TI  - Health services under siege: the case for clinical process redesign.
AB  - *Public health services are struggling to cope with rising demand. *Strain on
      health services manifests as longer waiting lists for surgery, queuing in the
      emergency departments, increased rates of adverse events, and delays in
      discharge, particularly for older patients. *Traditional responses are not
      resolving these problems. *Analysis shows that the day-to-day system processes
      underlying clinical care are poorly designed and do not produce a well planned,
      well coordinated patient journey. *Numerous disconnections along the continuum of
      care have a cumulative effect in obstructing patient flow and causing frustration
      for patients and staff. *Rigorous clinical process redesign methods can
      significantly improve performance, even in the face of rising demand.

PMID- 18341477
TI  - Trafficking properties and activity regulation of the neuronal glycine
      transporter GLYT2 by protein kinase C.
AB  - The neuronal glycine transporter GLYT2 controls the availability of the
      neurotransmitter in glycinergic synapses, and the modulation of its function may
      influence synaptic transmission. The active transporter is located in membrane
      rafts and reaches the cell surface through intracellular trafficking. In the
      present study we prove that GLYT2 constitutively recycles between the cell
      interior and the plasma membrane by means of a monensin-sensitive trafficking
      pathway. Also, a regulated trafficking can be triggered by PMA. We demonstrate
      that PMA inhibits GLYT2 transport by causing net accumulation of the protein in
      internal compartments through an increase of the internalization rate. In
      addition, a small increase of plasma membrane delivery and a redistribution of
      the transporter to non-raft domains is triggered by PMA. A previously identified
      phorbol-ester-resistant mutant (K422E) displaying an acidic substitution in a
      regulatory site, exhibits constitutive traffic but, in contrast with the wild
      type, fails to show glycine uptake inhibition, membrane raft redistribution and
      trafficking modulation by PMA. We prove that the action of PMA on GLYT2 involves
      PKC (protein kinase C)-dependent and -independent pathways, although an important
      fraction of the effects are PKC-mediated. We show the additional participation of
      signalling pathways triggered by the small GTPase Rac1 on PMA action. GLYT2
      inhibition by PMA and monensin also take place in brainstem primary neurons and
      synaptosomes, pointing to a GLYT2 trafficking regulation in the central nervous
      system.

PMID- 18341478
TI  - Haem oxygenase-1 gene transfer protects retinal ganglion cells from
      ischaemia/reperfusion injury.
AB  - RGC (retinal ganglion cell) death following ischaemic insult is the major cause
      of a number of vision-threatening diseases, including glaucoma. The aim of the
      present study was to evaluate the role of HO-1 (haem oxygenase-1) in the retina
      against IR (ischaemia/reperfusion) injury. Adenovirus-mediated HO-1 gene transfer
      (Adv-HO-1) was carried out by injection into the vitreous body to induce HO-1
      overexpression. At 3 weeks after transfection, levels of HO-1 expression, as
      measured by Western blot analysis, immunohistochemical staining and activity
      assay, were drastically up-regulated. Transient retinal ischaemia was induced by
      raising the intraocular pressure to 150 mmHg for 60 min. Untreated IR caused a
      significant decrease in RGC numbers at 3 and 7 days after reperfusion (76.1 and
      67.2% of control eyes with sham IR respectively; P<0.001). Eyes pretreated with
      Adv-HO-1 had less RGC loss on day 3 and 7 following reperfusion compared with
      control eyes injected with Adv-GFP (adenovirus containing a gene for green
      fluorescent protein; 94.3 and 88.2% respectively; P=0.007 and 0.001). SnP (tin
      protoporphyrin), an HO-1 inhibitor, counteracted the effects of Adv-HO-1. In
      conclusion, these findings provide evidence that augmentation of HO-1 enzyme
      overexpression by intravitreal injection is able to protect RGCs against IR
      induced damage.

PMID- 18341479
TI  - Cell-penetrating peptides: from molecular mechanisms to therapeutics.
AB  - The recent discovery of new potent therapeutic molecules which do not reach the
      clinic due to poor delivery and low bioavailability have made the delivery of
      molecules a keystone in therapeutic development. Several technologies have been
      designed to improve cellular uptake of therapeutic molecules, including CPPs
      (cell-penetrating peptides), which represent a new and innovative concept to
      bypass the problem of bioavailability of drugs. CPPs constitute very promising
      tools and have been successfully applied for in vivo. Two CPP strategies have
      been described to date; the first one requires chemical linkage between the drug
      and the carrier for cellular drug internalization, and the second is based on the
      formation of stable complexes with drugs, depending on their chemical nature. The
      Pep and MPG families are short amphipathic peptides, which form stable
      nanoparticles with proteins and nucleic acids respectively. MPG- and Pep-based
      nanoparticles enter cells independently of the endosomal pathway and efficiently
      deliver cargoes, in a fully biologically active form, into a large variety of
      cell lines, as well as in animal models. This review focuses on the structure
      function relationship of non-covalent MPG and Pep-1 strategies, and their
      requirement for cellular uptake of biomolecules and applications in cultured
      cells and animal models.

PMID- 18341480
TI  - Effect of glycosylation on the extracellular domain of the Ag43 bacterial
      autotransporter: enhanced stability and reduced cellular aggregation.
AB  - Autotransporters constitute the biggest group of secreted proteins in Gram
      negative bacteria and contain a membrane-bound beta-domain and a passenger domain
      secreted to the extracellular environment via an unusually long N-terminal
      sequence. Several passenger domains are known to be glycosylated by cytosolic
      glycosyl transferases, promoting bacterial attachment to mammalian cells. In the
      present study we describe the effect of glycosylation on the extracellular
      passenger domain of the Escherichia coli autotransporter Ag43alpha, which induces
      frizzy colony morphology and cell settling. We identify 16 glycosylation sites
      and suggest two possible glycosylation motifs for serine and threonine residues.
      Glycosylation stabilizes against thermal and chemical denaturation and increases
      refolding kinetics. Unexpectedly, glycosylation also reduces the stabilizing
      effect of Ca(2+) ions, removes the ability of Ca(2+) to promote cell adhesion,
      reduces the ability of Ag43alpha-containing cells to form bacterial amyloid and
      increases the susceptibility of the resulting amyloid to proteolysis. In
      addition, our results indicate that Ag43alpha folds without a stable
      intermediate, unlike pertactin, indicating that autotransporters may arrive at
      the native state by a variety of different mechanisms despite a common overall
      structure. A small but significant fraction of Ag43alpha can survive intact in
      the periplasm if expressed without the beta-domain, suggesting that it is able to
      adopt a protease-resistant structure prior to translocation across the membrane.
      The present study demonstrates that glycosylation may play significant roles in
      structural and functional properties of bacterial autotransporters at many
      different levels.

PMID- 18341481
TI  - Cholesterol binding is a prerequisite for the activity of the steroidogenic acute
      regulatory protein (StAR).
AB  - Steroidogenesis depends on the delivery of cholesterol from the outer to the
      inner mitochondrial membrane by StAR (steroidogenic acute regulatory protein).
      However, the mechanism by which StAR binds to cholesterol and its importance in
      cholesterol transport are under debate. According to our proposed molecular
      model, StAR possesses a hydrophobic cavity, which can accommodate one cholesterol
      molecule. In the bound form, cholesterol interacts with hydrophobic side-chains
      located in the C-terminal alpha-helix 4, thereby favouring the folding of this
      helix. To verify this model experimentally, we have characterized the in vitro
      activity, overall structure, thermodynamic stability and cholesterol-binding
      affinity of StAR lacking the N-terminal 62 amino acid residues (termed N-62
      StAR). This mature form is biologically active and has a well-defined tertiary
      structure. Addition of cholesterol to N-62 StAR led to an increase in the alpha
      helical content and T degrees (melting temperature), indicating the formation of
      a stable complex. However, the mutation F267Q, which is located in the C-terminal
      helix interface lining the cholesterol-binding site, reduced the biological
      activity of StAR. Furthermore, the cholesterol-induced thermodynamic stability
      and the binding capacity of StAR were significantly diminished in the F267Q
      mutant. Titration of StAR with cholesterol yielded a 1:1 complex with an apparent
      K(D) of 3 x 10(-8). These results support our model and indicate that StAR can
      readily bind to cholesterol with an apparent affinity that commensurates with
      monomeric cholesterol solubility in water. The proper function of the C-terminal
      alpha-helix is essential for the binding process.

PMID- 18341483
TI  - Gastric Cancer Consensus conference recommends Helicobacter pylori screening and
      treatment in asymptomatic persons from high-risk populations to prevent gastric
      cancer.
AB  - Gastric adenocarcinoma remains a common cause of death worldwide, and there is
      convincing evidence that this cancer is causally linked to Helicobacter pylori.
      The first Asian-Pacific Gastric Cancer Consensus brought together leading
      authorities in the field including the authors, and systematically reviewed all
      of the available evidence for the role of H. pylori, diet and other risk factors
      in this malignancy. The consensus conference boldly recommended population-based
      screening and treatment for H. pylori in particularly high-risk population
      settings. The evidence for these recommendations is summarized in this report,
      and the global and U.S. implications are considered.

PMID- 18341484
TI  - Recovery from gut flora sepsis in the Ancient World.

PMID- 18341485
TI  - Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene
      polymorphisms in Japanese patients.
AB  - OBJECTIVES: Autoimmune pancreatitis (AIP) is characterized by high serum IgG4
      concentrations, lymphoplasmacytic inflammation, and a favorable response to
      corticosteroid treatment. Although the HLA DRB1*0405-DQB1*0401 haplotype and Fc
      receptor-like 3 polymorphisms have been associated with AIP, the role of other
      genetic factors is largely unknown. As cytotoxic T-lymphocyte antigen 4 (CTLA4)
      polymorphisms have recently been linked with several autoimmune diseases, we
      sought to determine if CTLA4 polymorphisms and serum sCTLA4 levels were
      associated with AIP as well. METHODS: Five CTLA4 polymorphisms, located at -1722,
      -658, and -318 in the promoter, +49 in exon 1, and +6230 in the 3' untranslated
      region, were genotyped in 59 patients with AIP and 102 healthy subjects. Serum
      sCTLA4 levels were also determined in cohorts of 52 patients and 32 controls.
      RESULTS: Compared with healthy subjects, we found a significant increase in the
      +6230 G/G genotype (64%vs 42%, odds ratio [OR] 2.48, P= 0.011) in AIP patients.
      Haplotype 2, which had the +6230A, was associated with AIP resistance (OR 0.49,
      P= 0.011). The +49A/A and +6230A/A genotypes were associated with an enhanced
      risk of relapse (OR 5.45, P= 0.038 and OR 12.66, P= 0.022). Additionally, median
      serum sCTLA4 levels were significantly higher in patients with AIP (8.9 ng/mL)
      compared with healthy subjects (2.9 ng/mL, P < 0.001). The +6230 G/A polymorphism
      did not influence sCTLA4 levels in AIP patients. CONCLUSIONS: Our findings
      suggest that AIP is associated with a genetic polymorphism in CTLA4 and is
      positively correlated with serum sCTLA4 levels.

PMID- 18341486
TI  - Are regulatory molecules for T cells involved in the development of autoimmune
      pancreatitis?
AB  - Impaired regulatory functions such as CTLA4 on T cells and naive regulatory T
      cells may be involved in the development of AIP.

PMID- 18341487
TI  - IL23R and ATG16L1 SNPs in IBD: alphabet soup or something more?
AB  - The results of recently completed genome-wide association studies have rapidly
      advanced knowledge of inflammatory bowel disease (IBD) genetics. Several
      promising associations between IBD and gene variants have been identified with
      the two best replicated so far being variants in the IL23R and ATG16L1 genes.
      These findings highlight the importance of the immune system and interactions
      with intestinal microflora in the pathogenesis of IBD.

PMID- 18341488
TI  - Unstable composition of the fecal microbiota in ulcerative colitis during
      clinical remission.
AB  - BACKGROUND AND AIM: Studies have identified abnormal characteristics of the gut
      microbiota in patients with active IBD, but whether the changes are causal or
      secondary to inflammation remains uncertain. We investigated dynamics of fecal
      microbiota in ulcerative colitis (UC) during remission by genomic technology.
      PATIENTS AND METHODS: Patients in clinical remission and on stable maintenance
      mesalazine therapy were recruited (N = 33). Fecal samples were collected at
      regular intervals over a period of 1 yr. Sixteen patients who remained in
      remission and eight healthy controls were included in the analysis. Variable V6
      to V8 regions of the 16S rRNA gene in DNA extracts from fecal samples were
      amplified by polymerase chain reaction. Amplicons were separated by denaturant
      gradient gel electrophoresis, band profiles were compared by software, and
      similarity indices were calculated from densitometric curves. RESULTS: Band
      profiles showed unique patterns with low similarity index between individuals,
      suggesting host specificity in the predominant microbiota. Within the same
      individual, profiles were stable in controls but varied notably over time in
      patients. In controls, the similarity index was remarkably stable (78 +/- 8% mean
      +/- SD) over a period of 24 months. However, patients showed a steady decline in
      similarity index versus the initial profile, dropping down to 42 +/- 24% at month
      3 of follow-up and to 23 +/- 19% at month 12 (P < 0.001). Biodiversity of the
      dominant microbiota, as estimated by number of bands, was lower in patients (17
      +/- 4) than controls (23 +/- 4, P < 0.01). CONCLUSION: Molecular analysis of
      fecal bacteria in patients with inactive UC shows low biodiversity and temporal
      instability.

PMID- 18341489
TI  - The role of CARD15 mutations and smoking in the course of Crohn's disease in a
      Mediterranean area.
AB  - AIM: To evaluate the role of CARD15 mutations and smoking in the main events of
      Crohn's disease (CD). PATIENTS AND METHODS: A total of 182 patients with CD were
      included in a prospective study in order to evaluate the role of CARD15 mutations
      and smoking in the main outcomes of disease course: first operation and surgical
      recurrence. The following variables were evaluated in a univariable and
      multivariable analysis: age, sex, site of disease, pattern, smoking habit,
      extraintestinal manifestations, duration of disease, and CARD15 mutation. The
      Kaplan-Meier method for survival curves and Cox model for multivariable analysis
      were, respectively, used. RESULTS: A total of 110 patients were operated on and
      32 were reoperated on. The 7-yr cumulative free rate of surgery was 42% (95% CI
      34-51%). At multivariate analysis only stricturing and penetrating pattern were
      predictors of surgery (HR 1.7, 95% CI 1-2.8; HR 3.2, CI 1.8-5.5, respectively).
      The 7-yr cumulative free rate of reoperation was 75% (95% CI 0.52-0.88). At
      multivariable analysis in the model with any CARD15 mutation, only smoking habit
      at diagnosis (HR 3.6, 95% CI 1.4-9.1) was predictive of surgical recurrence. When
      single mutations were considered in the model smoking (HR 4.2, 95% CI 1.8-10.1)
      and L1007fs mutation (HR 2.9, 95% CI 1.1-7.3) were predictive of reoperation.
      CONCLUSIONS: In CD, smoking predicts recurrence after surgery. The role of CARD15
      mutations in the clinical course of CD remains undefined.

PMID- 18341490
TI  - Revised criterion for diagnosis of ineffective esophageal motility is associated
      with more frequent dysphagia and greater bolus transit abnormalities.
AB  - BACKGROUND: Ineffective esophageal motility (IEM) has been defined by the
      presence of > or = 30% liquid swallows with contraction amplitude < 30 mmHg
      (ineffective swallows) in the distal esophagus ("old" IEM). A recent study with
      combined multichannel intraluminal impedance and manometry (MII-EM) raised the
      question whether the manometric diagnosis of IEM should be based on a new
      definition: > or = 50% ineffective liquid swallows ("new" IEM). The aim of this
      study was to evaluate the association between the number of ineffective liquid
      swallows and symptoms and bolus transit in patients with "new" or "old" IEM who
      underwent MII-EM studies using 10 liquid and 10 viscous swallows. MATERIALS AND
      METHODS: There were 150 patients with "old" IEM included in the study. The
      patients diagnosed with "old" IEM (N = 150) (group A) were compared with those
      who retained a manometric diagnosis of IEM by the new definition (N = 101) (group
      B). The patients who did not retain their manometric diagnosis of IEM by the new
      definition (N = 49) (group C) were compared with group B. IEM was characterized
      as mild (normal bolus transit for both liquid and viscous swallows), moderate
      (abnormal bolus transit either for liquid or viscous swallows), or severe
      (abnormal bolus transit for both liquid and viscous swallows). RESULTS: There was
      no statistical difference in frequency of mild, moderate, or severe IEM and
      frequency of symptoms between group A and B. Group C had a significantly higher
      frequency of mild IEM and significantly lower frequency of severe IEM than group
      B. Heartburn (25.7%vs 10.2%, P= 0.03) and dysphagia (24.8%vs 12.3%, P= 0.08)
      showed a trend towards a greater frequency in group B than in group C.
      CONCLUSION: Our study indicates that IEM with > or = 50% ineffective liquid
      swallows is frequently associated with bolus transit abnormalities and esophageal
      symptoms. Our results underscore the rationale for using the new definition of
      IEM.

PMID- 18341491
TI  - Spatiotemporal characteristics of acid refluxate and relationship to symptoms in
      premature and term infants with chronic lung disease.
AB  - BACKGROUND AND OBJECTIVES: The prevalence of gastroesophageal reflux (GER) is
      high among infants with chronic lung disease (CLD), and the associated pathogenic
      mechanisms are not clear. The relationship of symptoms to the extent or duration
      of acid reflux events (AREs) is not well known in preterm or term infants. Our
      aim was to evaluate the relationship between spatial (height) and temporal
      (duration) characteristics of AREs (pH <4.0) with symptoms in CLD. We tested the
      hypothesis that in infants with CLD, AREs into the pharynx are associated with
      increased symptom occurrence and delayed clearance. METHODS: Nine infants born at
      29.8 +/- 5.5 wk gestation (mean +/- SD, range 24.7-39.0 wk) with CLD were
      evaluated for GER at 49.7 +/- 8.0 wk postmenstrual age (mean +/- SD, range 39.9
      67.4 wk). Esophageal manometry was first performed to determine the nares-lower
      esophageal sphincter (LES) distance. A pH-impedance probe was placed at 87% of
      the nares-LES distance, and a recording was performed for about 24 h at cribside.
      Symptoms (respiratory, sensory, and movement) were documented by nurses that were
      blinded to the pH-impedance recordings. A symptom was considered associated with
      an ARE if it occurred 2 min before, during, or 2 min after the ARE. The proximal
      extent and associated clearance mechanisms were correlated with symptom
      sensitivity index (SSI = number of AREs with symptoms/total AREs *100). Multiple
      logistic regression methods, analysis of variance (ANOVA) models, and chi(2)
      tests were performed. Data are described as median, mean +/- SD, or %. RESULTS: A
      total of 511 AREs, based on pH-Impedance methods, were analyzed from 203 h of
      recordings in the nine infants. The distal esophagus was the maximal height
      reached in 80% of AREs (P < 0.001, compared to other esophageal segments).
      Overall 33% of the AREs were associated with symptoms, and an SSI of 77% was
      noted with high AREs into the pharynx. The average acid clearance time was
      prolonged with symptomatic AREs versus nonsymptomatic AREs by 3.5-fold (P <
      0.001). CONCLUSIONS: The occurrence and frequency of symptoms with AREs depend on
      the most proximal extent of the ARE and the acid clearance time.

PMID- 18341492
TI  - Molecular genetics of gastroenteropancreatic neuroendocrine tumors.
AB  - Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are usually sporadic;
      however, familial (inherited) syndromes, such as the multiple endocrine neoplasia
      1 (MEN-1) syndrome, von Hippel-Lindau (VHL) syndrome, neurofibromatosis (NF-1),
      as well as tuberous sclerosis, may be associated with proximal intestinal and
      pancreatic NETs. For example, 25% of gastrinoma patients have MEN-1 syndrome.
      Over the last two decades, the genetic basis of tumorigenesis for these familial
      syndromes has been clearly identified, providing clinicians with useful screening
      tools for affected families. Also, over the last few years, advanced molecular
      genetic techniques, such as comparative genomic hybridization (CGH) and loss of
      heterozygosity (LOH) analyses, have detected some differences in genomic
      aberrations among various types of NETs. Whether these chromosomic alterations
      have implications in the treatment of patients and the outcome of the disease is
      still unclear.

PMID- 18341497
TI  - Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's
      esophagus.

PMID- 18341498
TI  - Nonmetastatic cancer of the colon associated with pyogenic liver abscess.

PMID- 18341499
TI  - The appropriateness of colorectal cancer screening by fecal occult blood tests.

PMID- 18341500
TI  - Acute phosphate nephropathy--comment on Sica et al.

PMID- 18341501
TI  - Hiccups: an unrecognized symptom of esophageal cancer?

PMID- 18341502
TI  - Blood cultures of 19 Crohn's disease patients.

PMID- 18341503
TI  - Inflammatory bowel disease: lessons from animal models.

PMID- 18341504
TI  - Polyflex or ultraflex stents to treat peptic refractory esophageal strictures?

PMID- 18341505
TI  - Low colorectal cancer screening rates and primary care physicians' behavior.

PMID- 18341506
TI  - The impact of medical therapy for inflammatory bowel disease on pregnancy
      outcome.

PMID- 18341507
TI  - Colorectal cancer screening in Latin America: the Panama experience.

PMID- 18341508
TI  - Septic pylephlebitis mimicking biliary obstruction.

PMID- 18341509
TI  - Phosphate nephropathy.

PMID- 18341510
TI  - Response to Schiano et al. Hepatoportal sclerosis as a cause of noncirrhotic
      portal hypertension in patients with HIV.

PMID- 18341511
TI  - Frequency and pattern of endoscopic recurrence in Crohn's disease patients with
      ileocolonic resection using a laparoscopic versus laparotomic approach: a
      prospective longitudinal study.

PMID- 18341512
TI  - Effects of perinatal, combined exposure to 1,4-dichlorobenzene and 1,1-dichloro
      2,2-bis(p-chlorophenyl)ethylene on rat female reproductive system.
AB  - Prenatal or early postnatal exposure to some synthetic chemicals may affect the
      later reproductive system of the offspring. 1,4-Dichlorobenzene (DCB) is used as
      an air freshener and a moth repellent and 1,1-dichloro-2,2-bis(p-chlorophenyl)
      ethylene (p,p'-DDE) is a persistent metabolite of 1,1,1-trichloro-2,2-bis(p
      chlorophenyl)ethane that was used as a pesticide before. DCB concentrations of
      residential air and oral p,p'-DDE intake through marine products are demonstrated
      to be rather high in Japan. Such situations lead to high body burden of these
      pollutants in pregnant women. Consequently, foetuses and neonates will be exposed
      much more to DCB and p,p'-DDE via the mother. Therefore, the effects of the
      perinatal, combined exposure to DCB and p,p'-DDE on the female reproductive
      system have been investigated in mature rat female offspring of dams ingesting 25
      p.p.m. DCB (approximately 2 mg/kg) and 125 p.p.m. p,p'-DDE (approximately 10
      mg/kg) during the gestational and lactational period. Sexual maturation was fully
      developed in the rat female offspring perinatally exposed to DCB and/or p,p'-DDE
      through maternal exposure. The combined effect of DCB and p,p'-DDE was observed,
      and the ovarian weight was seen to decrease to approximately 80% of the control
      rat in matured female offspring following perinatal exposure to DCB and p,p'-DDE.
      This alteration might lead to reproductive dysfunction in matured female
      offspring. However, biological relevance of the alteration in the ovary remained
      uncertain in the present study. Further investigations concerning the
      reproductive function and mechanistic implication are required for elucidating
      the combined effects of perinatal exposure to DCB and p,p'-DDE on the later
      female reproductive system entirely.

PMID- 18341513
TI  - Antioxidant and acetylcholinesterase response to repeated malathion exposure in
      rat cerebral cortex and hippocampus.
AB  - The wide use of the organophosphate insecticide malathion is accompanied by the
      risk of human exposure, especially in developing countries, which underlines the
      need of basic studies in this area. Some reports have shown that low doses of
      malathion, in a repeated treatment regimen, are unable to reduce
      acetylcholinesterase (AChE) activity in the rat brain, in contrast to the
      inhibitory effect in acute treatment. In order to investigate if AChE activity is
      affected by repeated low-level malathion administration, female Wistar rats were
      exposed to malathion (50 and 100 mg/kg, intraperitoneally) for 3 consecutive
      days. Exposure to malathion 50 mg/kg did not affect AChE activity, as previously
      observed. Contrary to expectation, 100 mg/kg malathion produced a significant
      increase in AChE activity in both cerebral cortex and hippocampus. Besides AChE
      inhibition, malathion may act as a pro-oxidative agent by interfering with
      antioxidant defences, as shown by a decrease of glutathione peroxidase and
      glutathione reductase activity in the cerebral cortex (100 mg/kg malathion).
      These effects are in contrast to response in the hippocampus where the increase
      in AChE activity correlates positively with the antioxidant defences, while the
      opposite was found in the cerebral cortex. These data indicate that, with low
      doses, and after a short period of exposure, malathion induces an up-regulation
      of AChE activity, a pattern similar to that found in the hippocampus for the
      antioxidant defences studied. The cerebral cortex was more vulnerable to
      malathion, as reflected in a decrease of two antioxidant enzymes. This study
      indicates that (i) alternatively to AChE inhibition, interference with the
      antioxidant defence system may be another important target for malathion
      toxicity; (ii) hippocampal and cortical AChE activity in rats can be increased
      after repeated low-dose malathion exposure. This response suggests the occurrence
      of a pathophysiological response in order to maintain the homeostasis of the
      cholinergic system in these cerebral structures.

PMID- 18341514
TI  - N-acetylcysteine effects on genotoxic and oxidative stress parameters in
      cirrhotic rats with hepatopulmonary syndrome.
AB  - The aim of this study was to evaluate the potential antioxidant effects of N
      acetylcysteine in hepatopulmonary syndrome, a complication of cirrhosis, using an
      experimental model of common bile duct ligation in rats. Male Wistar rats were
      divided into four experimental groups: CBDL (animals submitted to common bile
      duct ligation); Sham (animals submitted to simulated common bile duct ligation);
      Sham + N-acetylcysteine, and CBDL + N-acetylcysteine. N-acetylcysteine (10 mg/kg,
      intraperitoneally) was administered for 2 weeks starting on day 14 after surgery.
      Some alterations in the liver integrity were investigated by evaluation of serum
      enzymes aspartate aminotransferase, alanine aminotransferase, alkaline
      phosphatase, and arterial blood gases. Lipoperoxidation by thiobarbituric acid
      reactive substances assay, superoxide dismutase activity and total nitrates was
      measured as parameters of oxidative stress, performed on lung homogenates.
      Micronucleus assay in bone marrow and comet assay in lung, liver and blood were
      performed to assess the genotoxic effects by oxidative stress. The results showed
      an improvement in the enzymatic parameters and arterial blood gases, a reduction
      of lipoperoxidation and in the total nitrates after treatment with N
      acetylcysteine. Histological analysis showed vasodilatation in the lung, which
      was reversed by N-acetylcysteine. Micronuclei frequency and DNA damage in lung
      and liver were increased in the CBDL group. N-Acetylcysteine caused no genotoxic
      effect and did not influence the induction of micronucleus in bone marrow and DNA
      damage in lung and liver. The results suggest protective effects after treatment
      with N-acetylcysteine in cirrhotic rats with hepatopulmonary syndrome.

PMID- 18341515
TI  - Metyrapone and mifepristone reverse recognition memory loss induced by
      spontaneous morphine withdrawal in mice.
AB  - Morphine withdrawal leads to an increase in corticosterone concentration in
      plasma, and cognitive deficits are found after withdrawal. Evidence indicates
      that glucocorticoid hormones affect memory. The aim of the current study was to
      evaluate the effects of metyrapone and mifepristone on memory deficit following
      spontaneous morphine withdrawal. Memory was tested by using the object
      recognition task. The novel object recognition task was carried out in a square
      wooden open-field apparatus using objects. The test was comprised of three
      sections: habituation for 15 min., first trial for 12 min. and test trial for 5
      min. In this learning paradigm, the difference in exploration between a
      previously seen object and a novel object is taken as an index of memory
      performance (recognition index - RI). Male mice were made dependent by increasing
      doses of morphine (30-90 mg/kg) subcutaneously twice daily for 3 days. RI was
      assessed 4 hr after the last dose of morphine on the third day. Mifepristone (50
      and 100 mg/kg) and metyrapone (12.5 and 25 mg/kg) were used subcutaneously before
      the first trial and effects were compared to control values. Metyrapone (25
      mg/kg) and mifepristone (50 mg/kg) improved RI to 34.8 +/- 10.8% and 25.4 +/-
      11.7%, respectively, which are significantly different from control values (RI = 
      14.8 +/- 10.7%, P < 0.05). These results show that increased glucocorticoid
      concentration may be involved in memory deficit caused by morphine withdrawal.
      Metyrapone by inhibiting glucocorticoid formation, and mifepristone by inhibiting
      glucocorticoid receptors may be useful for preventing memory deficit following
      morphine withdrawal.

PMID- 18341516
TI  - Melatonin uptake in prostate cancer cells: intracellular transport versus simple
      passive diffusion.
AB  - Melatonin, an indole mainly synthesized in the pineal gland during the dark
      phase, plays a role as an endogenous antioxidant and an anticancer agent in many
      tumors. Melatonin, at pharmacological concentrations, inhibits cell growth and
      induces neuroendocrine differentiation in prostate cancer cells. Classically it
      has been considered that melatonin enters freely into most of cells by passive
      diffusion through the cell membrane; however, there are few studies examining how
      melatonin is taken up by cancer cells. The aim of the present paper was to study
      the uptake of melatonin into human androgen-dependent LNCaP and androgen
      independent PC-3 prostate cancer cells. Increased concentrations of melatonin
      induced a rapid and transitory rise in intracellular melatonin content in both
      cell types, with a peak of maximal content at 6 hr after melatonin addition,
      following a rhythmic uptake; melatonin was found in both cytoplasm and nuclear
      fractions. Inhibition of protein or RNA synthesis partially blocked melatonin
      uptake in both cell lines. Interestingly, melatonin pulse incubation led to a
      higher uptake after four cycles of pulse incubation. Neither extracellular
      Ca(2+)/K(+) alterations nor the presence of bovine serum albumin or charcoal
      stripped serum modified the profile of melatonin uptake. On the contrary,
      chemical binding of melatonin to BSA totally prevented melatonin from entering
      into cells. The present data support the hypothesis that a facilitated diffusion
      or an active process rather than simple passive diffusion through the cell
      membrane is the major mechanism in melatonin uptake by prostate cancer cells and
      it accounts for its intracellular concentration (350 nM-3.3 microM), which is
      related to its anti-tumor actions.

PMID- 18341517
TI  - Potential role of tryptophan derivatives in stress responses characterized by the
      generation of reactive oxygen and nitrogen species.
AB  - To face physicochemical and biological stresses, living organisms evolved
      endogenous chemical responses based on gas exchange with the atmosphere and on
      formation of nitric oxide (NO(*)) and oxygen derivatives. The combination of
      these species generates a complex network of variable extension in space and
      time, characterized by the nature and level of the reactive oxygen (ROS) and
      nitrogen species (RNS) and of their organic and inorganic scavengers. Among the
      latter, this review focusses on natural 3-substituted indolic structures.
      Tryptophan-derived indoles are unsensitive to NO(*), oxygen and superoxide anion
      (O(2)(*-)), but react directly with other ROS/RNS giving various derivatives,
      most of which have been characterized. Though the detection of some products like
      kynurenine and nitroderivatives can be performed in vitro and in vivo, it is more
      difficult for others, e.g., 1-nitroso-indolic compounds. In vitro chemical
      studies only reveal the strong likelihood of their in vivo generation and
      biological effects can be a sign of their transient formation. Knowing that 1
      nitrosoindoles are NO donors and nitrosating agents indicating they can thus act
      both as mutagens and protectors, the necessity for a thorough evaluation of
      indole-containing drugs in accordance with the level of the oxidative stress in a
      given pathology is highlighted.

PMID- 18341518
TI  - C-terminal domains within human MT1 and MT2 melatonin receptors are involved in
      internalization processes.
AB  - Melatonin, a molecule implicated in a variety of diseases, including cancer,
      often exerts its effects through G-protein-coupled melatonin receptors, MT(1) and
      MT(2). In this study, we sought to understand further the domains involved in the
      function and desensitization patterns of these receptors through site-directed
      mutagenesis. Two mutations were constructed in the cytoplasmic C-terminal tail of
      each receptor subtype: (i) a cysteine residue in the C-terminal tail was mutated
      to alanine, thus removing a putative palmitoylation site, and a site possibly
      required for normal receptor function (MT(1)C7.72A and MT(2)C7.77A) and (ii) the
      C-terminal tail in the MT(1) and MT(2) receptors was truncated, removing the
      putative phosphorylation and beta-arrestin binding sites (MT(1)Y7.64 and
      MT(2)Y7.64). These mutations did not alter the affinity of 2-[(125)I]
      iodomelatonin binding to the MT(1) or MT(2) receptors. Using confocal microscopy,
      it was determined that the putative palmitoylation site (cysteine residue) did
      not play a role in receptor internalization; however, this residue was essential
      for receptor function, as determined by 3',5'-cyclic adenosine monophosphate
      (cAMP) accumulation assays. Truncation of the C-terminal tail of both receptors
      (MT(1)Y7.64 and MT(2)Y7.64) inhibited internalization as well as the cAMP
      response, suggesting the importance of the C-terminal tail in these receptor
      functions.

PMID- 18341519
TI  - Quality of pharmacotherapy and outcomes for older veterans discharged from the
      emergency department.
AB  - OBJECTIVES: To determine whether suboptimal pharmacotherapy increases the risk of
      adverse outcomes in older adults discharged from the emergency department (ED).
      DESIGN: Retrospective, cohort study. SETTING: Academically affiliated Veterans
      Affairs Medical Center. PARTICIPANTS: Nine hundred forty-two veterans aged 65 and
      older discharged from the ED. MEASUREMENTS: The primary independent variable,
      suboptimal pharmacotherapy, was based on drugs-to-avoid criteria, drug-drug
      interactions, drug-disease interactions, or failure to satisfy explicit quality
      indicators (QIs). An adverse outcome was defined as one or more repeat ED visits
      or hospitalizations or death within 90 days of ED discharge. RESULTS: Four
      hundred twenty-one patients were prescribed a new medication at ED discharge. Of
      these, 134 (31.8%) had suboptimal pharmacotherapy; 49 (11.6%) were prescribed a
      drug to avoid, 53 (12.6%) received a drug that introduced a new drug-drug
      interaction, 24 (5.7%) were given a drug that introduced a drug-disease
      interaction, and 74 (17.6%) did not have a QI satisfied. Overall, 320 patients
      (34.0%) experienced an adverse outcome within 90 days. Multivariable analyses
      suggested a trend toward greater risk of adverse outcomes in patients with
      suboptimal pharmacotherapy (hazard ratio=1.32, 95% confidence interval=0.95,
      1.84). CONCLUSION: A substantial number of older male veterans discharged from
      the ED may be at risk for adverse events due to suboptimal prescribing and
      inadequate medication monitoring. Efforts to improve the quality of
      pharmacotherapy in this vulnerable population are warranted.

PMID- 18341520
TI  - Effect of Paclitaxel-eluting versus sirolimus-eluting stents on coronary
      restenosis in Korean diabetic patients.
AB  - BACKGROUND: With the introduction of drug-eluting stents (DES), the angiographic
      rates of restenosis have reduced dramatically but less prominently in diabetic
      patients. We compared the effects of sirolimus-eluting stents (SES) versus
      paclitaxel-eluting stents (PES) on 6-month angiographic and clinical outcomes in
      Korean diabetic patients. METHOD: Diabetic patients with de novo coronary lesions
      (169 patients with 190 lesions) were randomly assigned to either SES or PES in
      six different cardiovascular centers from April 2005 to January 2006. Patients
      with vessel size >2.0 mm and < or =2 vessel diseases requiring < or =2 DES
      implantation were included in the study. RESULTS: Baseline clinical and
      angiographic characteristics were similar between the two groups. At 6-month
      follow-up, the late lumen loss (0.26 +/- 0.76 in the SES group vs. 0.39 +/- 0.92
      mm in the PES group, P = 0.356) and the rate of binary restenosis (2.8%[n = 2] in
      the SES group vs. 6.9%[n = 5] in the PES group, P = 0.441) showed no significant
      differences. Rates of death (1.2%[n = 1] in the SES group vs. 1.2%[n = 1] in the
      PES group, P = 1.000), myocardial infarction (1.2%[n = 1] in the SES group vs.
      1.2%[n = 1] in the PES group, P = 1.000), and target lesion revascularization
      (2.4%[n = 2] in the SES group vs. 4.8%[n = 4] in the PES group, P = 0.443) were
      similar in both groups during 6 months of follow-up. CONCLUSION: The use of
      either SES or PES demonstrated similar 6-month angiographic and clinical outcomes
      in Korean diabetic patients with coronary artery disease.

PMID- 18341521
TI  - Early results of balloon dilatation of the stenotic bovine jugular vein graft in
      the right ventricular outflow tract in children.
AB  - The aim of this study was to evaluate the early results of interventional balloon
      dilatation of stenotic bovine jugular vein (BJV) grafts implanted for
      reconstruction of the right ventricular outflow tract (RVOT) in children.
      METHODS: From May 2001 to December 2005, 153 BJV grafts were implanted in
      children in our institution. An average of 16.9 (7.6-41.1) months after
      implantation, 17 balloon dilatations in a significant stenosis proximal (n = 1),
      distal anastomosis (n = 8), BJV valve (n = 3), or at multiple sites (n = 5) were
      performed in 15 children (male:female = 9:6) with a mean age of 3.9 (0.8-13.0)
      years. Balloon diameter was 75-133.3% (mean 100.3) of the original BJV size. Mean
      follow-up was 8.8 (2 days to 22.8 months) months. RESULTS: In 10 interventions
      (58.8%) the instantaneous peak gradient was reduced below 50 mmHg. A balloon
      diameter > or =100% of the original BJV size correlated significantly with a
      successful intervention. No major complications, two minor (nonobstructive
      floating membranes at the dilatation site and one septicemia) occurred afterward.
      Freedom from reintervention after 6 months was 58.2% for all, 77.8% for
      dilatations of the proximal anastomosis and mixed stenotic lesions, and 33.3% for
      the distal anastomosis. CONCLUSION: Balloon dilatation of stenotic BJV grafts is
      safe and can significantly reduce the pressure gradient in two-thirds of
      interventions. Balloon diameters above the original graft size should be aimed
      for. The most frequent stenosis of the distal anastomosis tends to renarrow early
      after dilatation. Nevertheless, balloon dilatation should be considered in nearly
      every stenotic graft to gain time until a surgical or interventional graft
      exchange.

PMID- 18341522
TI  - Fluoroscopy-guided femoral artery puncture reduces the risk of PCI-related
      vascular complications.
AB  - BACKGROUND: In previous work by the Northern New England Cardiovascular Study
      Group, risk factors for vascular access site complications in percutaneous
      coronary intervention (PCI) were identified and a regional effort to reduce these
      complications was initiated. As part of this effort we considered making a
      regional recommendation that location of the femoral head as seen on fluoroscopy
      (fluoro) be used to help determine the site of femoral artery puncture.
      Therefore, we assessed the use of fluoro to determine whether it actually reduced
      the rate of vascular complications and shortened length of stay. METHODS: Data
      were collected prospectively on 2,651 consecutive PCIs at Eastern Maine Medical
      Center from 2000 to 2003 including use of fluoro, vascular access site
      complications (bleeding, pseudoaneurysm formation, hematoma, embolic event or
      thrombus, A-V fistula), and length of stay. RESULTS: Use of fluoro among eight
      interventionists was variable: 3 < 20%, 3 35-50%, 2 > 70%. Among all
      interventions, 48% were performed with fluoro to guide vascular access. The use
      of fluoro was associated with a significantly lower incidence of pseudoaneurysms
      (0.3% vs. 1.1%, P = 0.017) and any arterial injury (0.7% vs. 1.9%, P < 0.01).
      There was no significant difference in bleeding (1.6% vs. 1.8%, P = 0.69). For
      each physician, there were fewer vascular injuries when fluoro was used. Average
      length of stay was significantly lower among patients in the fluoro group (2.1
      days vs. 2.4, P < 0.01). CONCLUSION: We conclude that using fluoro to guide
      vascular access leads to lower complication rates and a shorter length of stay.
      This approach may become our regional standard of care.

PMID- 18341523
TI  - Retrograde crossing through the pedal arch for totally occluded tibial artery.
AB  - Critical limb ischemia is characterized by atherosclerotic disorder of the crural
      arteries. The occlusion of dorsalis pedis and paramalleolar posterior tibial
      arteries is a rare atherosclerotic pattern in the crural arteries. We present a
      successful case of retrograde posterior tibial artery crossing through the pedal
      arch after antegrade recanalization of occluded anterior tibial and dorsalis
      pedis arteries, leading to the achievement of complete infrapopliteal
      recanalization and wound healing.

PMID- 18341524
TI  - Characterisation of user-defined health status in older adults with intellectual
      disabilities.
AB  - BACKGROUND: Older adults with Intellectual Disabilities (ID) have an excess
      disease burden that standard health assessments are designed to detect. Older
      adults with ID have a broader concept of health with dimensions of well being in
      addition to absence of disease in line with the World Health Organization's
      health definition. We sought to characterise user-defined health status in a
      sample of older adults with ID. METHODS: We administered a user-led health
      assessment to 57 adults with ID aged 40 years and over. Cluster analysis on user
      defined health themes of participation, nutrition and hygiene/self-care
      identified clear separation of participants into a healthier and a less healthy
      group. RESULTS: Disease burden (P = 0.002) and medication use (P = 0.003) were
      greater in the less healthy group. The healthier group were taller (P = 0.005),
      stronger (P = 0.005) and had better vision (P < 0.001) than the less healthy
      group. Constipation (P = 0.014), urinary incontinence (P < 0.001) and faecal
      incontinence (P < 0.001) were commoner in the less healthy group. There were few
      significant differences between health groups on the majority of standard
      physical-examination items. CONCLUSIONS: There is considerable overlap between
      user-defined health and that assessed by standard instruments. In addition, user
      defined health encompasses aspects of physical fitness not captured by
      traditional disease-based health models.

PMID- 18341525
TI  - Health and sleep problems in Cornelia de Lange Syndrome: a case control study.
AB  - BACKGROUND: Self-injury, sleep problems and health problems are commonly reported
      in Cornelia de Lange Syndrome (CdLS) but there are no comparisons with
      appropriately matched participants. The relationship between these areas and
      comparison to a control group is warranted. METHOD: 54 individuals with CdLS were
      compared with 46 participants with intellectual disability (ID) of mixed
      aetiology who were similar in terms of degree of ID, mobility, age and gender
      using informant-based measures of health problems, sleep and self-injury.
      RESULTS: Participants with CdLS experienced significantly more current and
      lifetime health problems with eye problems and gastrointestinal disorders
      prominent. Although 55% of those with CdLS experienced sleep problems this
      prevalence was not different from the comparison group. Sleep disorder was not
      associated with self-injury in the CdLS group, skin problems were associated with
      severity of self-injury but not presence. DISCUSSION: People with CdLS experience
      a range of significant health problems and have more health concerns than others
      with the same degree of ID. Although this has been well documented in the past,
      the current high prevalence of health concerns indicates the need for regular
      health assessment and appropriate intervention.

PMID- 18341526
TI  - A comparison of patients with intellectual disability receiving specialised and
      general services in Ontario's psychiatric hospitals.
AB  - BACKGROUND: Over the years, the closure of institutions has meant that
      individuals with intellectual disabilities (IDs) must access mainstream (i.e.
      general) mental health services. However, concern that general services may not
      adequately meet the needs of patients with ID and mental illness has led to the
      development and implementation of more specialised programmes. This study
      compares patients with ID receiving specialised services to patients with ID
      receiving general services in Ontario's tertiary mental healthcare system in
      terms of demographics, symptom profile, strengths and resources and clinical
      service needs. METHOD: A secondary analysis of Colorado Client Assessment Record
      data collected from all tertiary psychiatric hospitals in the province was
      completed for all 371 inpatients with ID, from both specialised and general
      programmes. RESULTS: Inpatients in specialised programmes were more likely to
      have a diagnosis of mood disorder and were less likely to have a substance abuse
      or psychotic disorder. Individuals receiving specialised services had higher
      ratings of challenging behaviour than those in more general programmes. The two
      groups did not differ significantly in terms of recommended level of care,
      although more inpatients from specialised programmes were rated as requiring
      Level 4 care than inpatients from general programmes. CONCLUSIONS: In Ontario,
      inpatients in specialised and general programmes have similar overall levels of
      need but unique clinical profiles that should be taken into consideration when
      designing interventions for them.

PMID- 18341527
TI  - A strong note of caution in using matrix metalloproteinase-1 and its inhibitor,
      TIMP-1 in serum as biomarkers in systolic heart failure.

PMID- 18341528
TI  - Endogenous sex hormones and C-reactive protein in healthy postmenopausal women.
AB  - BACKGROUND: Oral oestrogen replacement therapy increases levels of C-reactive
      protein (CRP). CRP is an established strong predictor of cardiovascular events.
      It is unknown whether endogenous oestrogen levels are associated with CRP. We
      therefore studied the relationship between endogenous sex hormones and CRP in
      healthy postmenopausal women emphasizing the role of body composition as
      peripheral fat is both a main source of oestrogen production after menopause and
      an endocrine tissue with inflammatory activities. SUBJECTS AND METHODS: The study
      population comprised 889 women participating in the PROSPECT study, an ongoing
      population-based cohort study. Information on risk factors was collected by
      questionnaires and clinical examination. Endogenous sex hormone levels and CRP
      were measured with double antibody radio immuno assay (RIA) from fasting plasma
      samples. In this cross-sectional study, associations between risk factors and
      lnCRP were studied using linear regression models. RESULTS: Increases in oestrone
      and free oestradiol levels and the free androgen index were related to an
      increase in lnCRP of 1.19, 1.23 and 1.21 mg dL(-1) respectively. Body mass index
      (BMI), waist circumference and physical activity were strongly related to CRP
      levels, independent of age and other cardiovascular risk factors. Levels of all
      sex steroids but dehydroepiandrostenedione decreased with age. In age-adjusted
      analyses, an increase in waist circumference or BMI by one quartile was
      associated with a 1.28-fold and 1.26-fold increase in CRP. The relationship
      between endogenous hormones and CRP was modestly attenuated but remained highly
      significant after adjustment for body composition, physical activity and other
      traditional cardiovascular risk factors. CONCLUSIONS: Our findings show that in
      postmenopausal women high levels of endogenous oestrogenic and androgenic sex
      steroids coincide with high CRP levels. This was only explained in part by
      markers of body composition or intra-abdominal fat.

PMID- 18341529
TI  - L-arginine preferentially dilates stenotic segments of coronary arteries thereby
      increasing coronary flow.
AB  - BACKGROUND AND OBJECTIVES: Oxidized LDL cholesterol and cytokines increase
      arginase and decrease nitric oxide (NO) synthase expression in human endothelial
      cells, leading to a decrease in NO production. In arteriosclerotic plaques,
      characterized by increased oxidized LDL and cytokine levels, a sustained local NO
      reduction might enhance sensitivity of the downstream guanylyl cyclase system
      towards an acute NO increase. We tested whether application of the NO synthase
      substrate l-arginine (l-arg, 150 micromol min(-1)) or the NO donor isosorbide
      dinitrate (ISDN; 0.3 mg) preferentially dilates stenotic coronary artery segments
      (CS) subsequently increasing poststenotic coronary blood flow (CBF) in patients
      with coronary artery disease (CAD). DESIGN, SETTING AND SUBJECTS: Changes in
      coronary diameter and circumferential surface area were assessed by quantitative
      coronary angiography (QCA) in a nonstenotic upstream segment, the CS, downstream
      the CS and in a reference vessel (n = 24). CBF was estimated in a subset of 13
      patients by QCA and intracoronary Doppler. RESULTS: CS ranged from 62% to 89% (77
      +/- 5%). l-arg increased minimal luminal diameter of the stenotic segment from
      0.98 +/- 0.06 to 1.14 +/- 0.07 mm (P < 0.05) without affecting other coronary
      segments. Poststenotic CBF increased by 24 +/- 3%. ISDN dilated all segments
      again with a predominance of CS (25 +/- 4%) and increased poststenotic CBF by 38
      +/- 9%. In a multifactorial anova, a medication with an angiotensin-converting
      enzyme inhibitor (decreasing inflammation and radical formation) and a ratio of
      LDL/HDL <3.5 were predictive for an l-arg-induced dilation. CONCLUSION: The
      increase in poststenotic CBF without affecting nondiseased arteries highlights
      the therapeutic potential of l-arg in patients with CAD.

PMID- 18341530
TI  - Plasma exchange for the management of the catastrophic antiphospholipid syndrome:
      importance of the type of fluid replacement.

PMID- 18341531
TI  - Circulating matrix metalloproteinase 9 levels in relation to sampling methods,
      femoral and carotid atherosclerosis.
AB  - OBJECTIVES: To examine whether circulating levels of matrix metalloproteinase 9
      (MMP-9) were associated with ultrasound-assessed intima-media thickness (IMT) and
      echolucent plaques in the carotid and femoral arteries. To examine preanalytical
      sources of variability in MMP-9 concentrations related to sampling procedures.
      SUBJECTS AND DESIGN: Plasma and serum MMP-9 levels were compared with ultrasound
      assessed measures of femoral and carotid atherosclerosis, in a cross-sectional
      study of 61-year-old men (n = 473). Preanalytical sources of variability in MMP-9
      levels were examined in 10 healthy subjects. Main outcome measures were
      circulating levels of MMP-9 in serum and plasma, IMT of the carotid and femoral
      arteries, and plaque status based on size and echolucency. SETTING: Research unit
      at university hospital. RESULTS: Plasma concentrations of total and active MMP-9
      were associated with femoral artery IMT independently of traditional
      cardiovascular risk factors, and were higher in subjects with moderate to large
      femoral plaques. Plasma MMP-9 concentration was higher in men with echolucent
      femoral plaques (P = 0.006) compared with subjects without femoral plaques. No
      similar associations were found for carotid plaques. MMP-9 concentrations were
      higher in serum than in plasma, and higher when sampling was performed with
      Vacutainer than with syringe. MMP-9 levels in serum were more strongly associated
      with peripheral neutrophil count compared with MMP-9 levels in plasma.
      CONCLUSIONS: Plasma MMP-9 levels were associated with atherosclerosis in the
      femoral artery, and total MMP-9 concentration was higher in men with echolucent
      femoral plaques. The choice of sample material and sampling method affect the
      measurements of circulating MMP-9 levels.

PMID- 18341532
TI  - Cutaneous abscess and bacteremia due to Serratia ficaria.

PMID- 18341533
TI  - Leukocytosis associated with low leukocyte alkaline phosphatase score following
      intravenous steroid therapy for atopic dermatitis.

PMID- 18341534
TI  - Infliximab for the treatment of severe pustular psoriasis: 6 years later.

PMID- 18341535
TI  - Necrotizing fasciitis following intramuscular diclofenac injection.

PMID- 18341536
TI  - Reported sexually transmitted infections in Swedish Internet-using men and women.
AB  - Although the Internet has become a forum for making sexual contacts, and has been
      associated with increased sexually transmitted infection (STI) transmission, we
      have little information of history of STIs in Internet-based samples. The
      Internet behaviours that are associated with STI acquisition are poorly
      understood. We analysed STI histories reported by 904 Swedish men and 931 Swedish
      women who responded to an Internet-based survey on sexual behaviour in 2002:
      16.6% of men and 22.5% of women reported a lifetime history of STIs, with
      Chlamydia being the most common for both genders. 3% of men and 5% of women who
      reported an STI, indicated that they had had more than one. Sources of the STI,
      where known, were Internet-acquired partners in only 3% of cases. There were no
      differences between men and women with or without an STI history regarding the
      kind of online sexual activities they engaged in, how they found sexual material
      online, and the reasons they engage in sexual activities. These rates are similar
      to those reported in a national random study of sexuality in Sweden. Contrary to
      prior research, these results suggest no relationship between STI and specific
      Internet characteristics usage patterns. These data suggest that the Internet is
      not yet a major source of STIs in Swedish men and women. Given these STI
      histories, the Internet may be a useful medium to include in STI prevention
      efforts.

PMID- 18341537
TI  - Redefining colour of Indian skin.

PMID- 18341538
TI  - Subcision in acne scar with and without subdermal implant: a clinical trial.
AB  - BACKGROUND: Subcision is a procedure that has been reported to be beneficial in
      treatment of acne scars. OBJECTIVE: This stady aims to assess the efficacy of
      subcision in the treatment of rolling acne scars and evaluate a novel subdermal
      filler 'absorbable plain catgut suture' with subcision. METHODS: Twenty-two
      patients with rolling acne scars underwent subcision, 20 of whom completed
      treatment and follow-up period. One side of the face underwent subcision and
      another side subcision with subdermal implant. The patients and investigators'
      assessment of improvement were both recorded. RESULTS: Subcision showed mild
      improvement in about 60% of patient and moderate improvement in about 40% of
      them. The rate of response showed no significant difference with the use of
      subdermal implant. The side-effects of local oedema, bruising and infection were
      all transient. CONCLUSIONS: Subcision seems to be a safe method to correct the
      rolling acne scars with long-term improvement. However, the subdermal implant led
      to no significant superior results.

PMID- 18341539
TI  - Disturbed gastrointestinal motility and decreased interstitial cells of Cajal in
      diabetic db/db mice.
AB  - BACKGROUND AND AIM: Diabetes mellitus (DM) often causes gastrointestinal
      dysmotility. Interstitial cells of Cajal (ICC), which express c-kit receptor
      tyrosine kinase (KIT), are considered the pacemaker cells for gastrointestinal
      movement. The present study was designed to determine the role of ICC in the
      pathogenesis of gastroenteropathy in type 2 DM. METHODS: We examined C57BL/KsJ
      db/db mice as a model for type 2 DM. Gastrointestinal motility was evaluated by
      measuring gastric emptying, whole gut transit time, and isometric tension of the
      isolated small intestine. The area of KIT-positive cells in the gastrointestinal
      tract was examined by image analysis of fluorescent immunohistochemistry. The
      mRNA expression of KIT ligand, stem cell factor (SCF), in the gastrointestinal
      tract was quantified by real-time reverse transcription-polymerase chain reaction
      (RT-PCR). RESULTS: Compared with 12-week-old db/+m control mice, diabetic db/db
      mice of the same age exhibited delayed gastric emptying, prolonged whole gut
      transit time, irregular frequency of isometric tension in the small intestine,
      smaller areas of KIT-positive cells in the antrum, small intestine, and colon,
      and lower mRNA expression levels of SCF in the small intestine and colon.
      CONCLUSIONS: We demonstrated disturbed gastrointestinal motility in db/db mice
      with reduced areas of ICC and expression of SCF. Our results suggest the
      involvement of ICC in the gastroenteropathy of type 2 DM.

PMID- 18341540
TI  - Correlation of transforming growth factor beta-1 gene polymorphisms C-509T and
      T869C and the risk of gastric cancer in China.
AB  - BACKGROUND AND AIM: As an important cytokine that modulate the cell cycle, the
      involvement of transforming growth factor beta-1 (TGF-beta1) in carcinogenesis
      has been extensively studied for many years. Literatures have demonstrated that
      TGF-beta1 gene polymorphisms may alter the risk of various cancers, such as lung,
      prostate and breast. To investigate whether polymorphisms of the TGF-beta1 gene
      can modify the risk of gastric cancer, we conduct this hospital-based, case
      control study. METHODS: One hundred and sixty-seven cases and 193 gender, age
      matched healthy controls were enrolled in this case-control study. TGF-beta1
      polymorphisms C-509T and T + 869C were identified by PCR-RFLP and ARMS-PCR
      protocols, respectively. RESULTS: Significantly different distributions of both
      genes were demonstrated between the case and control. Variant genotypes -509CT, 
      509TT, +869TC and +869CC were associated with increased risk of gastric cancer (P
      = 0.001, OR = 2.54; P = 0.016, OR = 2.09; P < 0.001, OR = 3.46; P < 0.001, OR =
      4.04, respectively). With haplotype analysis, wild type CT (-509C and +869T) led
      to a lower frequency in case than that in control (P < 0.001), while haplotype TC
      was more frequent in case than in control (P < 0.001). Multiple logistic
      regression analysis revealed that individuals with haplotype TC had an increased
      likelihood of developing gastric cancer (OR = 3.19, 95%CI = 1.72-5.90).
      CONCLUSIONS: Our findings imply that -509C > T and +869T > C gene polymorphisms
      in TGF-beta1 may be a critical risk factor of genetic susceptibility to gastric
      cancer in the Chinese population.

PMID- 18341541
TI  - Inbreeding depression and outbreeding depression in Digitalis purpurea: optimal
      outcrossing distance in a tetraploid.
AB  - An optimal crossing distance exists within plant populations if inbreeding and
      outbreeding depression operate simultaneously. In a population of tetraploid
      Digitalis purpurea, maternal plants were pollinated with donors at four
      distances: 0 (self-pollination), 1, 6 and 30 m. Lifetime fitness of F1 progeny
      was investigated in greenhouse experiments, and significant inbreeding and
      outbreeding depression were detected at five vs. three life history traits.
      Inbreeding depression increased at later life stages, whereas outbreeding
      depression was relatively constant. The existence of within-population
      outbreeding depression suggests substantial genetic structuring at moderate
      distances in D. purpurea, and corroborates recent findings of significant
      outbreeding depression in F1 progeny in polyploids. The moderate inbreeding
      depression found in this predominately outcrossing population supports the notion
      that effects of inbreeding are less severe in polyploids than in diploids.

PMID- 18341542
TI  - Analysis of range expansion in two species undergoing character displacement: why
      might invaders generally 'win' during character displacement?
AB  - Ecological character displacement occurs when interacting species diverge in
      resource use and associated traits in response to selection to minimize resource
      competition between them. Yet, when resource quality is asymmetric, the species
      that monopolizes the more profitable resource following character displacement
      may have higher fitness and therefore be deemed the 'winner'. Here, we ask: does
      the winner tend to be the resident species (i.e. the earlier inhabitant of the
      geographic region where character displacement occurred) or the invader (i.e. the
      subsequent inhabitant of the region)? We focus on two spadefoot toad species that
      have undergone character displacement. Previous studies revealed that Spea
      bombifrons gains the higher quality resource following character displacement;
      consequently, Spea multiplicata must use the lower quality resource, and as a
      result, experiences negative fitness consequences. Where the two species have
      undergone character displacement, three lines of evidence implicate S. bombifrons
      as the invader: S. bombifrons possess lower haplotype and nucleotide diversity;
      they do not exhibit isolation by distance (in contrast to S. multiplicata); and
      they display much higher population growth rates. We hypothesize that historical
      patterns of selection in its ancestral range pre-adapted S. bombifrons to evolve
      phenotypes capable of monopolizing the superior resource. Generally, because
      superior competitive abilities may facilitate successful invasions, invaders may
      be well positioned to win during character displacement.

PMID- 18341543
TI  - Deliberate self-harm within an international community sample of young people:
      comparative findings from the Child & Adolescent Self-harm in Europe (CASE)
      Study.
AB  - BACKGROUND: Deliberate self-harm among young people is an important focus of
      policy and practice internationally. Nonetheless, there is little reliable
      comparative international information on its extent or characteristics. We have
      conducted a seven-country comparative community study of deliberate self-harm
      among young people. METHOD: Over 30,000 mainly 15- and 16-year-olds completed
      anonymous questionnaires at school in Australia, Belgium, England, Hungary,
      Ireland, the Netherlands and Norway. Study criteria were developed to identify
      episodes of self-harm; the prevalence of self-harm acts and thoughts, methods
      used, repetition, reasons given, premeditation, setting for the act, associations
      with alcohol and drugs, hospitalisation, and whether other people knew, were
      examined. RESULTS: Self-harm was more than twice as common among females as males
      and, in four of the seven countries, at least one in ten females had harmed
      herself in the previous year. Additional young people had thought of harming
      themselves without doing so. More males and females in all countries except
      Hungary cut themselves than used any other method, most acts took place at home,
      and alcohol and illegal drugs were not usually involved. The most common reasons
      given were 'to get relief from a terrible state of mind' followed by 'to die',
      although there were differences between those cutting themselves and those taking
      overdoses. About half the young people decided to harm themselves in the hour
      before doing so, and many did not attend hospital or tell anyone else. Just over
      half those who had harmed themselves during the previous year reported more than
      one episode over their lifetime. CONCLUSIONS: Deliberate self-harm is a
      widespread yet often hidden problem in adolescents, especially females, which
      shows both similarities and differences internationally.

PMID- 18341544
TI  - Models and determinants of vocabulary growth from kindergarten to adulthood.
AB  - BACKGROUND: Increasing evidence suggests that childhood language problems persist
      into early adulthood. Nevertheless, little is known about how individual and
      environmental characteristics influence the language growth of individuals
      identified with speech/language problems. METHOD: Individual growth curve models
      were utilised to examine how speech/language impairment and environmental
      variables (socioeconomic status, family separation, and maternal factors)
      influence vocabulary development from age 5 to 25. Participants were taken from a
      community sample of children initially diagnosed with speech/language problems at
      age 5 and their sex- and age-matched controls. RESULTS: The language impaired
      group had significantly poorer receptive vocabulary than the speech impaired and
      control groups throughout the 20-year period. Family income was a significant
      predictor of vocabulary growth when considered separately, but ceased to be a
      predictor when language impairment status was taken into account. Maternal
      education and family separation were determinants of vocabulary at age 5, over
      and above language impairment status. CONCLUSION: Language impairment is a
      significant risk factor for vocabulary development from childhood to adulthood.
      Individuals with speech impairment were less impaired on receptive vocabulary
      than individuals with language impairment. Further investigation into maternal
      and familial risk factors may provide targets for early intervention with
      children at risk for language impairment.

PMID- 18341545
TI  - No differences between group versus individual treatment of childhood anxiety
      disorders in a randomised clinical trial.
AB  - BACKGROUND: The present study compares an individual versus a group format in the
      delivery of manualised cognitive-behavioural therapy (FRIENDS) for children with
      anxiety disorders. Clinically referred children (aged 8 to 12) diagnosed with
      Separation Anxiety Disorder (n = 52), Generalised Anxiety Disorder (n = 37),
      Social Phobia (n = 22) or Specific Phobia (n = 16) were randomly assigned to
      individual (n = 65) or group (n = 62) treatment. METHOD: Analyses were conducted
      separately for the intent-to-treat sample and the sample of children who
      completed treatment. Analyses included chi-square comparisons and regression
      analyses with treatment format as a predictor. RESULTS: Forty-eight percent of
      the children in the individual versus 41% in the group treatment were free of any
      anxiety disorder at post-treatment; 62% versus 54% were free of their primary
      anxiety disorder. Regression analyses showed no significant difference in outcome
      between individual and group treatment. CONCLUSIONS: Children improved in both
      conditions. Choice between treatments could be based on pragmatic considerations
      such as therapeutic resources, referral rates, and the preference of the parents
      and the child.

PMID- 18341546
TI  - Early risk indicators of internalizing problems in late childhood: a 9-year
      longitudinal study.
AB  - BACKGROUND: Longitudinal studies on risk indicators of internalizing problems in
      childhood are in short supply, but could be valuable to identify target groups
      for prevention. METHODS: Standardized assessments of 294 children's internalizing
      problems at the age of 2-3 years (parent report), 4-5 years (parent and teacher
      report) and 11 years (parent and teacher) were available in addition to risk
      indicators from the child, family and contextual domain. RESULTS: Low
      socioeconomic status, family psychopathology at child age 2-3, parenting stress
      at child age 4-5 years, and parents' reports of child internalizing problems at
      age 4-5 years were the strongest predictors of internalizing problems at the age
      of 11. If these early risk factors were effectively ameliorated through
      preventive interventions, up to 57% of internalizing cases at age 11 years could
      be avoided. CONCLUSIONS: Predictors from as early as 2-5 years of age are
      relevant for identifying children at risk of internalizing problems in late
      childhood. The methodological approach used in this study can help to identify
      children who are most in need of preventive interventions and help to assess the
      potential health gain and efficiency of such interventions.

PMID- 18341547
TI  - Early phonological and sociocognitive skills as predictors of later language and
      social communication outcomes.
AB  - BACKGROUND: Previous studies of outcome for children with early language delay
      have focused on measures of early language as predictors of language outcome.
      This study investigates whether very early processing skills (VEPS) known to
      underpin language development will be better predictors of specific language and
      social communication outcomes than measures of language itself. METHOD:
      Participants were 163 children referred to clinical services with concerns about
      language at 2;6-3;6 years and followed up at 4-5 years. Novel assessments of
      phonological and sociocognitive processing were administered at Time 1 (T1),
      together with a standardised test of receptive and expressive language, and
      parental report of expressive vocabulary. The language test was re-administered
      at Time 2 (T2), together with assessments of morphosyntax and parental reports of
      social communication. RESULTS: Intercorrelations at and between T1 and T2 were
      high, and dissociations were rare. Ordinal regressions were run, entering
      predictors singly and simultaneously. With the exception of the phonological
      task, every early measure on its own was significantly predictive of most
      outcomes, and receptive language was the strongest all-round predictor. Results
      of simultaneous entry, controlling for the effect of other predictors, showed
      that early language was the strongest predictor of general language outcome, but
      early phonology was the strongest predictor of a measure of morphosyntax, and
      early sociocognition the strongest predictor of social communication.
      CONCLUSIONS: Language measures which draw on a wide range of skills were the
      strongest overall predictors of general language outcomes. However, our VEPS
      measures were stronger predictors of specific outcomes. The clinical and
      theoretical implications of these findings are discussed.

PMID- 18341548
TI  - Personality of young adults born prematurely: the Helsinki study of very low
      birth weight adults.
AB  - BACKGROUND: Today, the first generations of very low birth weight (VLBW <or= 1500
      g) infants are entering adulthood but very little is known of their personality
      traits, associated with both psychopathological vulnerability and resilience.
      METHODS: In this cohort study we compared personality traits among young adults
      (age range 18 to 27 years, mean 21.4, SD 2.19) with VLBW (n = 158) with those of
      term-born controls (n = 168) of same gender, age, and maternity hospital. The
      participants completed the Neo-Personality Inventory. RESULTS: Of the five main
      traits, the VLBW participants scored significantly higher in conscientiousness
      (MD .1, 95% CI .0 to .3; p < .03), agreeableness (MD .2, 95% CI .0 to .3; p <
      .001), and lower in openness to experience (MD -.1, 95% CI -.2 to .0; p < .02).
      In addition, the VLBW group differed from the controls with regard to facets of
      neuroticism (lower hostility and impulsivity, ps < .05) and extraversion (less
      assertiveness p < .01). Furthermore, there were fewer undercontrolled personality
      profiles among the VLBW subjects (p < .01). All differences were independent of
      gender, age at assessment, parental education, individual school grade average,
      and maternal pre-eclampsia and smoking during pregnancy. CONCLUSIONS: Young
      adults born with VLBW showed markedly different personality traits compared with
      their controls. The VLBW group displayed less negative emotions, were more
      dutiful and cautious, and displayed more warmth in their social relationships
      than their term-born peers. We present two potential mechanisms underlying these
      findings. The first relates to parental influences and the other to evidence
      linking biological mechanisms associated with prematurity with personality
      characteristics in adulthood.

PMID- 18341549
TI  - Maternal separation anxiety as a regulator of infants' sleep.
AB  - BACKGROUND: The regulation of infants' sleep is determined not only by biological
      factors but by relational aspects too. This study focused on maternal separation
      anxiety and examined its association with sleep-wake regulation at 10 months of
      age. METHOD: In a community sample comprising 52 infants and their mothers, sleep
      was measured objectively with an activity monitor, as well as through
      questionnaires. The mothers reported on their own separation anxiety and on the
      child's perceived distress. RESULTS: The main finding was that maternal
      separation anxiety was linked to settling to sleep routines and to night-waking.
      The contribution of the mothers' own separation anxiety to their infants' night
      waking remained significant after controlling for the child's fussiness.
      CONCLUSIONS: Consistent with the transactional perspective, the current research
      documented an interplay between maternal separation anxiety and aspects of the
      child's sleep-wake transitions.

PMID- 18341550
TI  - Traumatic events and suicide-related outcomes among Mexico City adolescents.
AB  - BACKGROUND: We report the prevalence and associations between traumatic events
      and suicidal ideation, suicide plans and suicide attempts among Mexican
      adolescents. METHODS: The data are from a representative multistage probability
      household survey of 3,005 adolescents aged 12 to 17 years residing in the Mexico
      City Metropolitan Area that was carried out in 2005. We used discrete time
      survival analyses to model the net impact of retrospectively reported prior
      occurrence of traumatic events on ideation, plans and attempts, taking into
      account the onset of psychiatric disorders. RESULTS: Prevalence of suicidality
      was high among respondents with traumatic events, ranging from a 43% prevalence
      of suicidal ideation among those with a history of 'Being raped' to a 25%
      prevalence of suicide attempts among those that reported 'Purposely injured,
      tortured or killed someone.' In cross-sectional estimates, any traumatic event
      was associated with an increase of 3.2 times the odds of suicide ideation, 5.1
      times the odds of a plan and 6.6 times the odds of an attempt. Number of events
      was also associated with increasing suicidality such that those with three or
      more events were 13.7 times more likely to report a suicide attempt than those
      with none. Multivariate discrete time survival models that took into account a
      large number of demographic, suicide-related and psychiatric disorder variables
      reduced in strength but did not alter these basic relationships. CONCLUSIONS: We
      conclude that traumatic events such as rape and sexual assault have a profound
      impact upon suicidality and that this relationship is not entirely explained by
      the onset of psychiatric disorders. Comprehensive interventions for adolescent
      victims of traumatic events, especially those with a history of cumulative
      events, should include, but not be restricted to, treatment of any associated
      psychiatric disorder.

PMID- 18341551
TI  - Continuity of behavioral and emotional problems from pre-school years to pre
      adolescence in a developing country.
AB  - BACKGROUND: All previous longitudinal community studies assessing the continuity
      of child behavioral/emotional problems were conducted in developed countries.
      METHOD: Six hundred and one children randomly selected from a Brazilian birth
      cohort were evaluated for behavioral/emotional problems through mother interview
      at 4 and 12 years with the same standard procedure - Child Behavior Checklist
      (CBCL). RESULTS: CBCL Total Problem score presented a medium stability (r = .42)
      with externalizing problems showing higher stability and more homotypic
      continuity than internalizing problems. Of the children presenting deviant scores
      at the age of 4, only 31% remained deviant at the age of 12 (p < .001). A deviant
      CBCL Total Problem score at 12 years old was predicted by Rule-Breaking Behavior
      [OR = 7.46, 95% CI 2.76-20.19] and Social Problems [OR = 3.56, 95% CI 1.36-9.30]
      scores at 4 years of age. Either Rule-Breaking or Aggressive Behavior -
      externalizing syndromes - were part of the predictors for the three broad-band
      CBCL scores and six out of the eight CBCL syndromes. CONCLUSIONS:
      Behavioral/emotional problems in preschool children persist moderately up to pre
      adolescence in a community sample. Externalizing problems at the age of 4
      comprise the developmental history of most behavioral/emotional problems at pre
      adolescence. Our findings concur with findings from developed countries and are
      quite similar for continuity, stability and predictability.

PMID- 18341552
TI  - Predictors (0-10 months) of psychopathology at age 11/2 years - a general
      population study in The Copenhagen Child Cohort CCC 2000.
AB  - BACKGROUND: Epidemiological studies of mental health problems in the first years
      of life are few. This study aims to investigate infancy predictors of
      psychopathology in the second year of life. METHODS: A random general population
      sample of 210 children from the Copenhagen Child Birth Cohort CCC 2000 was
      investigated by data from National Danish registers and data collected
      prospectively from birth in a general child health surveillance programme. Mental
      health outcome at 1(1/2) years was assessed by clinical and standardised measures
      including the Child Behavior Check List 1(1/2)-5 (CBCL 1(1/2)-5), Infant Toddler
      Symptom Check List (ITSCL), Checklist for Autism in Toddlers (CHAT), Bayley
      Scales of Infant Development (BSID II), Mannheim Eltern Interview (MEI), Parent
      Child Early Relational Assessment (PC ERA) and Parent Infant Relationship Global
      Assessment Scale (PIR-GAS), and disordered children were diagnosed according to
      the International Classification of Diseases (ICD-10) and Diagnostic
      Classification Zero to Three (DC: 0-3). RESULTS: Deviant language development in
      the first 10 months of life predicted the child having any disorder at 1(1/2)
      years, OR 3.3 (1.4-8.0). Neuro-developmental disorders were predicted by deviant
      neuro-cognitive functioning, OR 6.8 (2.2-21.4), deviant language development, OR
      5.9 (1.9-18.7) and impaired social interaction and communication, OR 3.8 (1.3
      11.4). Unwanted pregnancy and parents' negative expectations of the child
      recorded in the first months of the child's life were significant predictors of
      relationship disturbances at 1(1/2) years. CONCLUSIONS: Predictors of neuro
      developmental disorders and parent-child relationship disturbances can be
      identified in the first 10 months of life in children from the general
      population.

PMID- 18341553
TI  - Characterization of Vibrio harveyi strains recovered from diseased farmed
      Senegalese sole (Solea senegalensis).
AB  - AIM: To characterize 16 Vibrio harveyi strains isolated from different epizootic
      outbreaks affecting farmed Senegalese sole. MATERIALS AND RESULTS: The Vibrio
      harveyi strains tested have broad phenotypic diversity based on their biochemical
      and exoenzymatic patterns, outer membrane proteins (OMP), extracellular product
      (ECP) patterns and presence of prophages. Lethal dose 50 (LD(50)) of the strains
      and in vitro antagonism tests with two probiotic strains were also determined.
      The OMP analysis revealed three different patterns (A, M and V). The
      electrophoretic analysis of the ECP showed two different groups. All strains
      considered virulent based on their LD(50) exhibited the same protein pattern in
      their ECP (pattern I), while all nonvirulent strains showed a different profile
      (pattern II). About 32% of the tested strains were positive for prophages,
      although a clear relationship between virulence and the presence of prophages has
      not been established. CONCLUSIONS: The results obtained have shown differences
      between virulent and avirulent strains isolated from diseased farmed Senegalese
      sole based on the protein patterns of their ECP. However, a clear relationship
      between virulence and presence of prophages has not been established.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The differences observed between virulent
      and nonvirulent strains could be used to design prophylactic strategies against
      diseases caused by V. harveyi in farmed Senegalese sole.

PMID- 18341554
TI  - Use of the modified Robbins device to study the in vitro biofilm removal efficacy
      of NitrAdine, a novel disinfecting formula for the maintenance of oral medical
      devices.
AB  - AIMS: To evaluate the use of the modified Robbins device (MRD) to test
      disinfection strategies against biofilms that form on oral medical devices and to
      test the biofilm removal efficacy of NitrAdine, a disinfectant for the
      maintenance of oral medical devices. METHODS AND RESULTS: Biofilms were grown on
      discs using the MRD and biofilms formed in this system were used to evaluate the
      efficacy of NitrAdine and to determine the optimal disinfection conditions. Our
      data indicate that the use of the MRD allows for the rapid and reproducible
      formation of high-density biofilms. Determination of the efficacy of NitrAdine
      revealed high activity against biofilms tested (e.g. >3 log reduction for Candida
      albicans and Staphylococcus aureus) and allowed the determination of the optimal
      conditions for its use. CONCLUSION: The high reproducibility and flexibility of
      the MRD make it an excellent candidate for standardized testing of disinfectants
      aimed at reducing biofilms on oral medical devices. Using this system, we were
      able to demonstrate that NitrAdine exhibits high activity against biofilms formed
      by the micro-organisms tested. SIGNIFICANCE AND IMPACT OF THE STUDY: Our data
      suggest that our procedure is appropriate for standardized testing of
      disinfectants aimed at reducing biofilms on oral medical devices.

PMID- 18341555
TI  - Vibrio parahaemolyticus serovar O3:K6 gastroenteritis in northeast Brazil.
AB  - AIMS: To examine the virulence factors and the genetic relationship isolates of
      the serogroup O3 of Vibrio parahaemolyticus in outbreaks of diarrhoea in the
      northeast region of Brazil. METHODS AND RESULTS: Eighteen samples of the O3:K6
      and O3:KUT serotypes of V. parahaemolyticus were analysed by multiplex polymerase
      chain reaction (m-PCR) for detection of the tl, tdh and trh genes, by random
      amplified polymorphic DNA (RAPD) using two primers, and by amplification of the
      rDNA 16S-23S region. The gene tl was amplified in all the samples, tdh in 16
      while trh in none; amplification of rDNA 16S-23S generated only one profile; each
      RAPD primer produced two amplification patterns allowing grouping two tdh(-)
      Kanagawa-negative isolates. CONCLUSIONS: V. parahaemolyticus with characteristics
      of the pandemic clone appears to be widely disseminated in the studied region.
      Because of the genetic uniformity of the isolates, elucidation of outbreaks or
      tracking the source of contamination by the present molecular techniques seems
      useless. SIGNIFICANCE AND IMPACT OF THE STUDY: Detection of V. parahaemolyticus
      with virulence potential of pandemic clone from two outbreaks and from several
      isolated gastroenteritis cases points out the need for inclusion of this micro
      organism in the Brazilian routine monitoring of the diarrhoeas for elucidation of
      their aetiology.

PMID- 18341556
TI  - A novel feeding method in commercial Baker's yeast production.
AB  - AIMS: The aim of this investigation was to determine a better leavening ability
      and shelf life for the same biomass yield of final product. METHODS AND RESULTS:
      A commercial fed-batch bioreactor equipped with circulation loop was used to
      study the effect of carbon source, molasses, profile on dough-leavening ability,
      shelf life and biomass yield of Baker's yeast, Saccharomyces cerevisiae. A set of
      32 commercial batches were performed to investigate the effect of sugar
      concentration and compare with 32 control experiments. CONCLUSIONS: Higher local
      sugar concentration in circulation loop resulted in a better leavening ability
      and shelf life for the same biomass yield of the final product. In addition, this
      method improved nitrogen assimilation which resulted in higher protein content.
      Increase in leavening ability and protein content could be a result of the higher
      levels of glycolytic enzymes. SIGNIFICANCE AND IMPACT OF THE STUDY: It was
      observed that this change resulted in considerable improvement in leavening
      ability and shelf life at a commercial scale. It must be emphasized that to
      improve product quality, it is not necessary to pursue classical mutagenesis and
      selection strategies. A high-quality product can be achieved only by optimizing
      the feeding profile and strategy.

PMID- 18341557
TI  - Comparison of Lactococcus garvieae strains isolated in northern Italy from dairy
      products and fishes through molecular typing.
AB  - AIMS: To investigate the genetic relatedness between Lactococcus garvieae strains
      isolated from fish and dairy samples collected in northern Italy, using random
      amplified polymorphic DNA (RAPD)-polymerase chain reaction (PCR), Sau-PCR and
      amplified fragment length polymorphism (AFLP). METHODS AND RESULTS: Eighty-one
      isolates from bovine and caprine dairy products (n = 53) and from diseased
      rainbow trouts and other fishes (n = 28) were examined. All methods showed a
      typeability of 100%, repeatability ranging from 84.4% to 97.5% and discriminatory
      powers from 0.798 to 0.986. Dairy and fish strains revealed a low genetic
      relatedness as they are often grouped into distinct clusters. RAPD analysis
      discriminated 52 genotypes when primer M13 was used, whereas with primer P5 only
      27 genotypes were identified. When Sau-PCR was performed, 13 genotypes were
      detected while AFLP analysis allowed the differentiation of 32 genotypes.
      CONCLUSION: L. garvieae strains isolated from dairy samples are generally not
      related to those collected from fish lactococcosis outbreaks. SIGNIFICANCE AND
      IMPACT OF THE STUDY: L. garvieae strains exhibit a genetic diversity related to
      the specific animal host they colonize. RAPD M13 fingerprinting proved to be a
      molecular tool for comparing isolates, whereas Sau-PCR and AFLP analyses were
      useful techniques to investigate the distribution of L. garvieae populations in
      the environment.

PMID- 18341558
TI  - Isolation of an unusual strain of Edwardsiella tarda from turbot and establish a
      PCR detection technique with the gyrB gene.
AB  - AIMS: The aim of this study was to report an unusual Edwardsiella tarda and
      develop an effective method to identify this bacterium. METHODS AND RESULTS:
      During the spring and summer of 2006, an epizootic occurred among cultured turbot
      (Scophthalmus maximus) in Qingdao, China. A gram-negative, rod-shaped bacterium
      (designated as LTB-4) was isolated from the infected fish, and was proved to be
      virulent to turbot. Based on the 16S rDNA sequencing and phenotypic tests, the
      bacterial pathogen was identified as E. tarda. Unlike those commonly described E.
      tarda strains, no flagellate was observed. Partial gyrB genes were amplified from
      E. tarda using the universal primers of gyrB genes and sequenced. The polymerase
      chain reaction (PCR) primers for the gyrB gene were designed specific to E.
      tarda. It revealed positive amplification of the gyrB fragment in E. tarda,
      whereas other bacterial species were negative. In addition, the technique enabled
      the recognition of E. tarda from diseased fish. CONCLUSIONS: The isolate was
      identified as E. tarda without flagellate and an effective method was developed
      to identify E. tarda based on using the gyrB gene as a taxonomic marker.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The unusual E. tarda was first reported in
      China and the PCR allowed the rapid and sensitive detection of E. tarda.

PMID- 18341559
TI  - Cross-contamination in the kitchen: effect of hygiene measures.
AB  - AIMS: To determine the effect of hygiene measures on cross-contamination of
      Campylobacter jejuni at home and to select a safe tracer organism for C. jejuni.
      METHODS AND RESULTS: Comparative tests were conducted with nonpathogenic
      Escherichia coli and Lactobacillus casei and L. casei was chosen as the safe
      tracer organism. Salads containing chicken breast fillet contaminated with a
      known number of C. jejuni and L. casei were prepared according to different cross
      contamination scenarios and contamination levels of salads were determined. Cross
      contamination could be strongly reduced when cleaning cutting board and cutlery
      with hot water (68 degrees C), but generally was not prevented using consumer
      style cleaning methods for hands and cutting board. CONCLUSIONS: Dish-washing
      does not sufficiently prevent cross-contamination, thus different cutting boards
      for raw meat and other ingredients should be used and meat-hand contact should be
      avoided or hands should be thoroughly cleaned with soap. Lactobacillus casei can
      be used as a safe tracer organism for C. jejuni in consumer observational
      studies. SIGNIFICANCE AND IMPACT OF THE STUDY: Cross-contamination plays an
      important role in the transmission of food-borne illness, especially for C.
      jejuni. This study delivers suitable data to quantitatively assess the risk of
      campylobacteriosis caused by cross-contamination and it shows the effect of
      different preventive hygiene measures.

PMID- 18341560
TI  - Study on the antimicrobial effect of silver-containing inner liners in
      refrigerators.
AB  - AIMS: To investigate the effect of silver-based antimicrobial material
      incorporated in the inner liners of refrigerators on food safety and quality.
      METHODS AND RESULTS: In the first stage, the bactericidal effect was tested in
      the laboratory. Silver-containing samples and control plates were inoculated with
      different bacterial suspensions and stored at various temperatures. After defined
      storage periods the bacterial reduction was calculated by comparing viable cell
      count on reference plates and on silver-containing plates. The reduction caused
      by the silver-containing material varied between 1.0 and 5.9 log(10) units,
      depending on bacterial strain, incubation time and temperature. In the second
      stage, food storage experiments have been carried out. Thus, perishable foods
      were stored in coated and untreated refrigerators. After certain time periods the
      products were analysed for their sensorial and microbiological characteristics. A
      clear drop in viable counts both on the refrigerator wall and on the food was
      demonstrated using the silver-based antimicrobial material. CONCLUSIONS: Silver
      prevents refrigerators from being a hot spot for contaminants that could be
      transferred upon contact with food. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      study provides original results regarding the antimicrobial activity of silver
      containing refrigerator surfaces.

PMID- 18341561
TI  - Silicon as a plant defence against insect herbivory: response to Massey, Ennos
      and Hartley.
AB  - 1. Silicon (Si) has received increased attention as a nutrient capable of
      providing some measure of defence for plants against fungal pathogens, and insect
      and mammalian herbivores. 2. On the basis of a study including two generalist
      insect folivores and a phloem feeder, Massey, Ennos & Hartley (2006; Journal of
      Animal Ecology, 75, 595-603) have drawn attention to a putative distinction
      between the effects of plant Si in defending against folivorous and phloem
      feeding insects. On the basis of their results they imply that phloem feeders are
      less likely to be adversely affected by increased plant Si than folivores. 3.
      However, in making this suggestion, Massey et al. have ignored many previous
      studies demonstrating a clear effect of plant Si on a range of phloem-feeding and
      some xylem-feeding insects, and that this effect stems not only from leaf
      mechanical properties based on opaline silica, but also from induced chemical
      defences seemingly mediated by soluble Si. 4. Furthermore, Massey et al. cannot
      claim that their study was the first demonstration of a direct effect of Si on
      insect herbivore preference and performance; there have been numerous earlier
      studies demonstrating this from folivores, stem borers, and phloem and xylem
      feeders. 5. We contend that current evidence indicates that Si is likely to be
      involved to a similar extent in enhancing resistance to all four insect feeding
      guilds and that any conclusion to the contrary is, at this stage, premature.

PMID- 18341562
TI  - Effect of xylitol and xylitol-fluoride lozenges on approximal caries development
      in high-caries-risk children.
AB  - AIM: To evaluate the effect of xylitol- and xylitol/fluoride-containing lozenges
      on approximal caries development in young adolescents with high caries risk.
      STUDY DESIGN: A 2-year double-blind trial with two parallel arms and a
      nonrandomized reference group. MATERIAL AND METHODS: One hundred and sixty
      healthy 10- to 12-year-old children with high caries risk were selected. After
      informed consent, they were randomly assigned into a xylitol and a
      xylitol/fluoride group. They were instructed to take two tablets three times a
      day (total xylitol and fluoride dose 2.5 g and 1.5 mg, respectively). The
      compliance was checked continuously and scored as good, fair, or poor. A
      reference no-tablet group was also selected (n = 70) for group comparison. The
      outcome measure was approximal caries incidence. RESULTS: The dropout rate was
      28%, and 41% exhibited a good compliance with the study protocol. No
      statistically significant differences in caries incidence could be found between
      the study groups (P > 0.05). Among a subgroup of children who demonstrated good
      compliance, the mean DeltaDMFSa value was significantly lower in the
      xylitol/fluoride group compared to the xylitol group, 1.0 +/- 2.3 vs. 3.3 +/- 4.6
      (P < 0.05), while no difference could be displayed between any of the study
      groups and the reference group (P > 0.05). CONCLUSION: The results from this 2
      year trial did not support a self-administered regimen of xylitol- or
      xylitol/fluoride-containing lozenges for the prevention of approximal caries in
      young adolescents with high caries risk.

PMID- 18341563
TI  - The changes in the T-lymphocyte subsets in a population of Turkish children with
      puberty gingivitis.
AB  - OBJECTIVE: The aim of the study was to investigate the number of CD4 and CD8 T
      lymphocytes, analyse subjects with gingivitis and those without, and determine
      the role of T lymphocytes in the pathobiology of puberty gingivitis. MATERIAL AND
      METHODS: Fifty individuals with and without puberty gingivitis were recruited for
      this study. The CD4(+) and CD8(+) T-lymphocyte counts were determined using flow
      cytometry on the biopsy samples, and the CD4(+)/CD8(+) ratio was calculated. At
      the same time, periodontal index scores were recorded to assess the periodontal
      status. Acquired data were analysed statistically using a paired t-test to
      compare laboratory values obtained before and after the treatment in individuals
      with puberty gingivitis and disease-free individuals. In addition, Pearson's
      correlation analysis was performed to investigate the relation between laboratory
      values and clinical measurements. RESULTS: The CD4(+)/CD8 ratio in gingival
      tissues obtained from test group was significantly higher (P < 0.05) than that
      found in the gingival tissue obtained from control group. We found that the
      CD4(+) and CD8(+) lymphocyte counts continued to increase significantly (P <
      0.001) and the CD4(+)/CD8(+) ratio continued to drop significantly (P < 0.05)
      after treatment in test group. CONCLUSIONS: T lymphocytes could play a
      significant role in the pathobiology of puberty gingivitis.

PMID- 18341564
TI  - Lidocaine 20% patch vs lidocaine 5% gel for topical anaesthesia of oral mucosa.
AB  - BACKGROUND: Topical anaesthetics are important to provide pain control at dental
      injection. AIM: The aim was to evaluate the effectiveness of the intraoral
      topical anaesthetics lidocaine 20% patch (DentiPatch) and lidocaine 5% gel.
      DESIGN: The randomized unblinded cross-over study included 31 patients (ten boys,
      21 girls) aged 13.5 +/- 2.5 years. Application of lidocaine patch or gel was
      randomly used at first and second visit in the upper premolar region. Heart rate
      was measured before and at each needle insertion after 2.5, 5, and 15 min and at
      injection after 15 min. Discomfort and pain were expressed in visual analogue
      scales (VAS). Paired t-test and Mann-Whitney U-test were used for statistic
      analyses. RESULTS: Heart rate at buccal injection decreased more when the patch
      was used (P = 0.0149). Heart rate was lower at the second visit (P = 0.0287).
      Patients expressed less discomfort when the patch was used on both buccal (P =
      0.0150) and palatal (P = 0.0391) site. Boys had lower heart rate and VAS pain
      scale ratings than girls. CONCLUSIONS: Good pain control can reduce the patients'
      anxiety level--expressed in heart rate--at the second appointment. The patch and
      gel seem to provide similar pain reduction at needle stick and injection of local
      anaesthetics.

PMID- 18341565
TI  - Effect of acid etching time on bond strength of an etch-and-rinse adhesive to
      primary tooth dentine affected by amelogenesis imperfecta.
AB  - BACKGROUND: Dentine affected by amelogenesis imperfecta (AI) is histologically
      altered following loss of the hypoplastic enamel and becomes hypermineralized,
      which would make bonding less predictable. AIM: This study examined the effect of
      etching time on the microtensile bond strength (microTBS) to AI-affected primary
      dentine. DESIGN: Flat coronal dentine surface was obtained from extracted AI
      affected and noncarious primary molars. Teeth were etched either for 15 or for 30
      s using 34% phosphoric acid. Prime & Bond NT (Dentsply De Trey), an etch-and
      rinse adhesive, was applied to dentine surfaces, air-dried and light-cured,
      followed by composite build-ups. The bonded teeth were sectioned into beams of
      0.8 mm(2) and stressed to failure under tension. Representative fractured beams
      from each group were examined under scanning electron microscopy. RESULTS: The
      extended etching time had an adverse effect on the microTBS for the normal
      dentine, while no significant difference was found for AI-affected dentine. When
      the AI-affected dentine was etched for 30 s, the fracture occurred in the
      demineralized dentine at the base of the hybrid layer. CONCLUSION: Bonding to AI
      affected dentine compromised the bonding of the etch-and-rinse adhesive. The
      bonding could not be improved by increasing etching time.

PMID- 18341566
TI  - Insulin resistance phenotypes and coronary artery disease in a native Pakistani
      cohort.
AB  - OBJECTIVE: To determine the relationship between insulin resistance (IR) and
      atheroma burden in Pakistanis. METHODS: A prospective case-control study of 400
      patients selected for the presence/absence of angiographic disease. Coronary
      atheroma burden was quantified and IR and cardiovascular risk factors were
      measured. RESULTS: The patients were divided into two groups by QuickI score.
      Waist circumference (90 +/- 10 vs. 90 +/- 9 cm; p = 0.7) was similar but the
      groups differed in body mass index (26.5 +/- 3.7 vs. 24.2 +/- 3.5 kg/m(2); p <
      0.001) and waist:hip ratio (0.94 +/- 0.09 vs. 0.90 +/- 0.06; p < 0.001). Lipid
      parameters showed similar high-density lipoprotein cholesterol (HDL-C) (0.77 +/-
      0.23 vs. 0.82 +/- 0.22 mmol/l; p = 0.1) differences in triglycerides [1.32 (0.08
      3.98) vs. 1.12 (0.37-3.61) mmol/l; p = 0.01], but no difference in low-density
      lipoprotein cholesterol (LDL-C) (2.75 +/- 1.00 vs. 2.90 +/- 0.94 mmol/l; p =
      0.14). In insulin-resistant patients C-reactive protein (CRP) [6.8 (0.3-175.1)
      vs. 3.9 (0.2-57.9) mg/l: p < 0.001], sialic acid (82 +/- 14 vs. 77 +/- 15 mg/l; p
      < 0.001) aspartate transaminase [24 (7-171) vs. 21 (7-83) IU/l; p < 0.001] and
      gamma-glutamyl transferase [27 (8-482) vs. 21 (7-168) IU/l; p = 0.005] levels
      were increased. In insulin-resistant patients (n = 187), coronary artery disease
      (CAD) burden correlated (r = 0.55) with age (beta = 1.62; p < 0.001), HDL-C (beta
      = -53.2; p < 0.001), lipoprotein (a) (beta = 11.4; p = 0.007), smoking (beta =
      7.98; p = 0.004), CRP (beta = 6.06; p = 0.03) and QuickI index (beta = -146; p =
      0.04). In contrast in insulin-sensitive patients (n = 178) CAD burden (r = 0.46)
      correlated with LDL-C (beta = 10.0; p = 0.02), CRP (beta = 7.13; p = 0.03), HDL-C
      (beta = -38.1; p = 0.03), and weakly with age (beta = 0.73; p = 0.07) and smoking
      (beta = 5.52; p = 0.09). CONCLUSIONS: Indian Asians show a dichotomous insulin
      resistance phenotype. Atheroma is associated with low HDL-C and inflammation
      associated in all but LDL-C is a factor in the insulin sensitive in contrast to
      age and extent of IR in the insulin resistant.

PMID- 18341567
TI  - Relevance between lipid metabolism-associated genes and rat liver regeneration.
AB  - AIM: Lipids are important in constituting cell structure and participating in
      many biological processes, particularly in energy supplementation to cells. The
      aim of the present study is to elucidate the action of lipid metabolism
      associated genes on rat liver regeneration (LR). METHODS: Lipid metabolism
      associated genes were obtained by collecting website data and retrieving related
      articles, and their expression changes in the regenerating rat liver were checked
      by the Rat Genome 230 2.0 array. RESULTS: In total, 280 genes involved in lipid
      metabolism were proven to be LR-associated by comparing the gene expression
      discrepancy between the partial-hepatectomy and sham-operation groups. The
      initial and total expression numbers of these genes occurring in the initial
      phase, G(0)/G(1) transition, cell proliferation, cell differentiation, and
      structure-functional rebuilding of LR were 128, 33, 135, 6, and 267, 147, 1026,
      306, respectively, illustrating that these genes were initially expressed mainly
      in the initiation stage and functioned in different phases. Upregulation (850
      times) and downregulation (749 times), as well as 25 types of expression
      patterns, showed that the physiological and biochemical activities were diverse
      and complicated in LR. CONCLUSION: According to the results of the chip
      detection, it was presumed that fatty acid synthesis at 24-66 h, leukotriene and
      androgen synthesis at 16-168 h, prostaglandin synthesis at 2-96 h, triglyceride
      synthesis at 18-24 h, glycosphingolipid synthesis at 0.5-66 h, metabolism of
      phosphatidyl inositol and sphingomyelin at 2-16 h, and cholesterol catabolism at
      30-168 h were enhanced. Throughout almost the whole LR, the genes participating
      in estrogen, glucocorticoid, and progesterone synthesis, and triglyceride
      catabolism were upregulated, while phospholipid and glycosphingolipid catabolism
      were downregulated.

PMID- 18341568
TI  - Decreased expression of thymidine phosphorylase/platelet-derived endothelial cell
      growth factor in basal cell carcinomas.
AB  - Thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor is
      associated with tumor angiogenesis. We evaluated the TP mRNA and protein
      expression in basal cell carcinomas (BCC) and in various skin tumors including
      numerous BCC histological simulants. Immunohistochemistry was performed on 99
      paraffin sections of formalin-fixed skin tumors using monoclonal antibodies (mAb)
      against TP. TP mRNA levels were measured by real time RT-PCR in whole BCCs (wBCC)
      and laser capture microdissected (LCM) BCC tumor cells. TP immunostaining was
      negative in all BCC variants and in most of the benign trichogeneic tumors
      studied. By contrast, TP was constantly immunodetected in actinic keratosis (AK),
      squamous cell carcinomas (SCC), syringomatous carcinomas (SC), basosquamous
      carcinomas (BSC) and melanomas. TP mRNA levels were low and statistically not
      different in wBCC and normal skin but were strongly downregulated in LCM-BCC as
      compared with LCM-normal epidermis. We concluded that (i) anti-TP mAb is an
      useful marker to differentiate BCC from AK, SCC, BSC and SC but not from
      trichoblastic tumors, (ii) the lack of TP protein expression in BCC tumoral cells
      is linked to transcriptional regulatory mechanisms, (iii) the low TP mRNA levels
      in whole BCC may be related to the low intra-tumoral microvessel density, the
      slow growth and the very low metastatic potential of these tumors.

PMID- 18341569
TI  - Anti-inflammatory and immune-regulatory mechanisms prevent contact
      hypersensitivity to Arnica montana L.
AB  - Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of
      Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)
      kappaB activation because of alkylation of the p65 subunit. Despite its known
      immunosuppressive action, Arnica has been classified as a plant with strong
      potency to induce allergic contact dermatitis. Here we examined the dual role of
      SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We
      tested the anti-inflammatory and allergenic potential of SL in the mouse contact
      hypersensitivity model. We also used dendritic cells to study the activation of
      NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different
      doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB
      activation and IL-12 production in dendritic cells at high concentrations, but
      had immunostimulatory effects at low concentrations. Contact hypersensitivity
      could not be induced in the mouse model, even when Arnica tinctures or SL were
      applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed
      contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene
      and activation of dendritic cells. However, contact hypersensitivity to Arnica
      tincture could be induced in acutely CD4-depleted MHC II knockout mice. These
      results suggest that induction of contact hypersensitivity by Arnica is prevented
      by its anti-inflammatory effect and immunosuppression as a result of immune
      regulation in immunocompetent mice.

PMID- 18341570
TI  - Tetracycline suppresses ATP gamma S-induced CXCL8 and CXCL1 production by the
      human dermal microvascular endothelial cell-1 (HMEC-1) cell line and primary
      human dermal microvascular endothelial cells.
AB  - Tetracyclines (TCN) have powerful anti-inflammatory properties in addition to
      their anti-microbial effects. These anti-inflammatory effects are thought to play
      a role in inhibiting cutaneous inflammation in patients with rosacea and acne;
      however, the mechanism(s) of this action remains poorly understood. We have
      previously shown that adenosine-5'-triphosphate (ATP)gamma S, a hydrolysis
      resistant ATP analogue, augments secretion of pro-inflammatory messengers by a
      human dermal microvascular endothelial cell line (HMEC-1). ATP released by the
      sympathetic nerves during stress may stimulate release of pro-inflammatory
      chemokines by dermal vessel endothelial cells, resulting in recruitment of
      inflammatory cells and exacerbation of inflammatory skin disease. Here we
      demonstrate that TCN inhibits ATP gamma S-induced release of pro-inflammatory
      mediators by HMEC-1 cells and primary human dermal microvascular endothelial
      cells. TCN dose-dependently inhibited ATP gamma S-induced augmentation of CXCL8
      (interleukin-8) and CXCL1 (growth-regulated oncogene-alpha) production by HMEC-1
      cells and primary human dermal endothelial cells in vitro. TCN and ATP gamma S
      did not affect HMEC-1 cell viability as determined by trypan-blue exclusion and
      cell counts. Inhibition of production of inflammatory mediators by endothelial
      cells may be one mechanism by which TCN improves inflammatory skin diseases. The
      ability to inhibit release of inflammatory mediators induced in HMEC-1 cells by
      purinergic agonists may be a useful way to screen for potential therapeutic
      agents for cutaneous inflammation.

PMID- 18341571
TI  - Staphylococcal enterotoxin B enhances a flare-up reaction of murine contact
      hypersensitivity through up-regulation of interferon-gamma.
AB  - BACKGROUND: We often see aggravation of eczematous skin lesions associated with
      bacterial infection, but the mechanism of this phenomenon is unclear.
      Staphylococcus aureus is known to colonize on the eczematous lesion and produce
      some exotoxins, which act as bacterial superantigens. OBJECTIVES: To investigate
      the potential role of superantigens in chronic dermatitis, we investigated the
      effect of staphylococcal enterotoxin B (SEB) on the skin reaction, the
      proliferative response and the cytokine production of local lymph node cells in
      the mouse model of contact hypersensitivity reaction. METHODS: Sensitized BALB/c
      mice were repeatedly challenged with dinitrofluorobenzene (DNFB), and
      intravenously injected with SEB and dinitrobenzne sulfonic acid sodium salt
      (DNBS). The ear swelling response was measured after DNBS injection. Cervical
      lymph node cells of those mice were cultured with DNBS in vitro. Their
      proliferative responses and the production of cytokines were assessed. RESULTS:
      SEB markedly enhanced the flare-up reaction of ear swelling induced by DNBS, the
      proliferative response of lymph node cells and the production of IFN-gamma. In
      contrast, the production of IL-5 was decreased. CONCLUSIONS: The present study
      may provide some clues for elucidating the mechanism involved in the exacerbation
      of dermatitis associated with staphylococcal infection.

PMID- 18341572
TI  - Fibulin-5 accelerates elastic fibre assembly in human skin fibroblasts.
AB  - Fibulin-5 null mice display abnormalities in the elastic fibres in the dermis. We
      postulated, therefore, that fibulin-5 might be a regulator of elastic fibre
      assembly and stability. To clarify the role of fibulin-5 in elastic fibre
      formation, we employed in vitro systems that allowed increasing expression of
      elastic fibre components by gene transduction using retroviral vector constructs.
      First, the human tropoelastin gene (ELN) was transduced into human dermal
      fibroblasts, which resulted in elevated gene expression. These cells were then
      cultured in monolayer, but the overexpression of ELN in this system did not alter
      the assembly of elastic fibres. However, incubation of fibroblasts with TGF-beta1
      resulted in elastic fibre accumulation, and the expression of fibulin-5 was
      enhanced by TGF-beta1. Thus, we overexpressed human fibulin-5 cDNA in dermal
      fibroblasts using a retroviral vector containing a cytomegalovirus (CMV)
      promoter. These cells deposited elastic fibres. These results suggest that
      fibulin-5 is a critical component in the control of elastic fibre assembly by
      dermal fibroblasts.

PMID- 18341573
TI  - K6PC-5, a novel sphingosine kinase activator, improves long-term ultraviolet
      light-exposed aged murine skin.
AB  - Sphingosine-1-phosphate (S1P), which is formed by phosphorylation of sphingosine
      through a process catalysed by sphingosine kinase (SK), is a multifunctional
      mediator of a variety of cellular responses including proliferation,
      differentiation, motility, and survival. K6PC-5, which was recently synthesized
      as a novel SK activator, is expected to increase S1P levels. Indeed studies have
      already demonstrated that K6PC-5 exhibits anti-aging effects on intrinsic aged
      murine skin by increasing fibroblasts, collagen synthesis, dermal thickness, and
      epidermal differentiation. However, photoaging and intrinsic aging have highly
      different clinical and histopathological properties. In this study, we developed
      a photoaged murine model by exposing mice that were 56 weeks old to ultraviolet
      (UV)B and UVA radiation for 8 weeks. We then investigated whether K6PC-5, as an
      SK activator, had anti-aging effects on photoaged murine skin in addition to its
      effects on intrinsic aged murine skin and determined the mechanism. K6PC-5
      increased dermal collagen density in photoaged skin through increases in
      fibroblasts and collagen production. Photoaged murine skin treated with K6PC-5
      showed an increase in stratum corneum (SC) integrity with increased
      corneodesmosome density and an improvement in barrier recovery rate. Matrix
      metalloproteinase 13 remained unchanged. These results indicate that topical
      application of K6PC-5 improves photoaged skin by improving skin barrier and
      increasing fibroblast count and function. In conclusion, K6PC-5, as an S1P
      activator, improves long-term UV-exposed aged skin as well as intrinsic aged
      skin.

PMID- 18341574
TI  - Skin surface electric potential as an indicator of skin condition: a new, non
      invasive method to evaluate epidermal condition.
AB  - We previously demonstrated that the skin surface electric potential, which has
      been long recognized as a parameter of emotional or physiological state, is
      generated by epidermal keratinocytes and is strongly associated with the ion
      concentration gradient in the epidermis. Thus, at temperatures below the
      threshold of sweating, the potential provides a measure of the epidermal ion
      concentration gradient, which in turn is related to epidermal homeostasis and
      pathology. In the present study, we established a new, non-invasive method to
      measure skin surface electric potential. In healthy skin, calcium ion was
      localized in the uppermost epidermis and the gradation disappeared by tape
      stripping. Skin surface potential was also disappeared by tape stripping.
      Moreover, environmental humidity affected the potential, whereas temporary
      hydration of the stratum corneum did not affect it. These results suggest that
      the skin surface electric potential may be an indicator of the pathophysiology of
      the living layer of epidermis, and thus may be useful as a new parameter to
      evaluate skin condition.

PMID- 18341575
TI  - An update on molecular aspects of the non-syndromic ichthyoses.
AB  - Ichthyosis includes a number of subtypes from congenital severe forms, such as
      harlequin ichthyosis (HI), to mild non-congenital forms, such as ichthyosis
      vulgaris. Recently, research into the pathomechanisms of ichthyoses has
      dramatically advanced and led to the identification of several causative genes
      and molecules underlying the genetic defects. In most types of ichthyosis,
      pathogenic mechanisms are associated with defects in skin barrier function. Three
      major components of the stratum corneum barrier are (i) intercellular lipid
      layers, (ii) cornified cell envelope and (iii) keratin-filaggrin degradation
      products. The causative molecules underlying ichthyosis subtypes include ABCA12,
      lipoxygenase-3, 12R-lipoxygenase, CYP4F2 homolog, ichthyin and steroid sulphatase
      and all these are thought to be related to the intercellular lipid layers.
      Transglutaminase 1 has a function in cornified cell envelope formation. Keratins
      1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and
      filaggrin are essential for formation of keratohyalin granules. In fact, loss of
      ABCA12 function leads to a defective lipid barrier in the stratum corneum,
      resulting in the HI phenotype and ABCA12 is a known keratinocyte lipid
      transporter associated with lipid transport in lamellar granules. Filaggrin gene
      mutations in ichthyosis vulgaris cause keratohyalin granule deficiency.
      Information concerning genetic defects and ichthyotic disease pathomechanisms are
      beneficial to develop effective therapy and provide information for genetic
      counselling including prenatal diagnosis for families affected by ichthyotic
      disease.

PMID- 18341576
TI  - Chinese herbal medicine (Tuhuai extract) exhibits topical anti-proliferative and
      anti-inflammatory activity in murine disease models.
AB  - While psoriasis is one of the most common skin disorders in humans, effective,
      safe and inexpensive treatments are still largely unavailable. Chinese herbal
      medicine (CHM) has been used for centuries for treating psoriasis and several
      reports claim that systemic administration of one such CHM, Tuhuai, mainly
      composed of flos sophorae, smilax glabra roxb and licorice, is effective in
      psoriasis. However, the mechanisms by which this CHM improves psoriasis are not
      yet clear. Two universal features of psoriasis are epidermal hyperplasia and
      inflammation. Moreover, drugs that specifically inhibit epidermal hyperplasia
      and/or inflammation are widely used to treat psoriasis. Here, we investigated
      whether topical applications of Tuhuai extract exhibit anti-proliferative and
      anti-inflammatory activities in two murine models of inflammatory dermatoses. To
      assess Tuhuai's potential anti-proliferative effect, we disrupted epidermal
      barrier function twice-daily for 4 days in normal hairless mice followed by
      topical applications of either 1% Tuhuai extract or Vehicle to both flanks
      immediately after each barrier perturbation. Changes in epidermal proliferation
      and apoptosis were evaluated by immunohistochemistry and TUNEL staining. To
      assess the anti-inflammatory effects of Tuhuai, both irritant (phorbol ester) and
      acute allergic contact dermatitis (oxazolone) models were used. Whereas topical
      Tuhuai extract did not alter epidermal proliferation or induce irritation in
      normal skin, it both reduced epidermal hyperplasia in the epidermal
      hyperproliferative model, and reduced inflammation in both irritant and allergic
      contact dermatitis models. As topical Tuhuai extract exhibits anti-proliferative
      and anti-inflammatory properties in a variety of human models of inflammatory
      dermatoses, Tuhuai could provide an effective, relatively safe and inexpensive
      therapeutic alternative for the treatment of inflammatory dermatoses, including
      psoriasis.

PMID- 18341577
TI  - Pilot study to assess the validity of the single assessment process as a
      screening tool for dental treatment needs in older people.
AB  - OBJECTIVE: To assess the feasibility of using a questionnaire-based needs
      assessment tool (D-E-N-T-A-L) to screen for dental treatment need as part of the
      single assessment process (SAP) for older people in Sheffield. MATERIALS AND
      METHODS: Test validation study comparing questionnaire-assessed and normative
      need in two consecutive samples of older adults: 48 living at home in the
      transition phase of older age and 29 frail older adults living in care homes.
      Each answered the six D-E-N-T-A-L questions as part of SAP and a dental
      examination was carried out within 2 weeks in participants' homes. Question
      defined need was then compared to the normative need. RESULTS: Questionnaire
      defined and normative need were high in both the transitional group (83% and 90%
      respectively) and the frail group (83% and 62%). These high levels of need meant
      that the sensitivity and positive predictive values of D-E-N-T-A-L were high, but
      the specificity and negative predictive values were low. CONCLUSION: The high
      levels of need in these patient groups suggests that preliminary questionnaire
      based screening is an unnecessary step. A clinical examination of all older
      people undergoing SAP may be necessary. Further research may be warranted on the
      use of questionnaires to assess dental treatment needs among people with
      different attendance patterns.

PMID- 18341578
TI  - Yeast biodiversity and dynamics during sweet wine production as determined by
      molecular methods.
AB  - In this study we investigated yeast biodiversity and dynamics during the
      production of a sweet wine obtained from dried grapes. Two wineries were selected
      in the Collio region and grapes, grape juices and wines during fermentations were
      analyzed by culture-dependent methods (plating on WLN medium) and culture
      independent methods (PCR-DGGE). Moreover, the capability of the Saccharomyces
      cerevisiae starter cultures to take over the fermentation was assessed by RAPD
      PCR. On WLN agar several species of non-Saccharomyces yeasts (Hanseniaspora,
      Metschnikowia, Pichia, Candida, Torulaspora and Debaryomyces), but also strains
      of S. cerevisiae, were isolated. After inoculation of the starter cultures, only
      colonies typical of S. cerevisiae were observed. Using PCR-DGGE, the great
      biodiversity of moulds on the grapes was underlined, both at the DNA and RNA
      level, while the yeast contribution started to become important only in the
      musts. Here, bands belonging to species of Candida zemplinina and Hanseniaspora
      uvarum were visible. Lastly, when the S. cerevisiae isolates were compared by
      RAPD-PCR, it was determined that only in one of the fermentations followed, the
      inoculated strain conducted the alcoholic fermentation. In the second
      fermentation, the starter culture was not able to promptly implant and other
      populations of S. cerevisiae could be isolated, most likely contributing to the
      final characteristics of the sweet wine produced.

PMID- 18341579
TI  - A new group of parasporal inclusions encoded by the S-layer gene of Bacillus
      thuringiensis.
AB  - Bacillus thuringiensis produces various groups of active proteins, such as Cyt,
      Vip and Parasporin, in addition to the Cry protein. In this study we show S-layer
      proteins to be a new group of parasporal inclusions of B. thuringiensis. The S
      layer consists of a two-dimensional lattice structure and is the outermost
      component of many archaeobacteria and eubacteria. The parasporal inclusion of B.
      thuringiensis strain CTC was found to be not a typical crystal protein encoded by
      the cry gene, but a proteinaceous inclusion encoded by the S-layer gene.
      Furthermore, the CTC-like strains (with their parasporal inclusions coded by the
      S-layer gene) are widely distributed and accounted for 25.4% of the B.
      thuringiensis strains tested. These strains constitute a new group of parasporal
      inclusions encoded by the S-layer gene of B. thuringiensis and shed new light on
      B. thuringiensis nontoxic strains.

PMID- 18341580
TI  - Resting spore formation of aphid-pathogenic fungus Pandora nouryi depends on the
      concentration of infective inoculum.
AB  - Resting spore formation of some aphid-pathogenic Entomophthorales is important
      for the seasonal pattern of their prevalence and survival but this process is
      poorly understood. To explore the possible mechanism involved in the process,
      Pandora nouryi (obligate aphid pathogen) interacted with green peach aphid Myzus
      persicae on cabbage leaves under favourable conditions. Host nymphs showered with
      primary conidia of an isolate (LC(50): 0.9-6.7 conidia mm(-2) 4-7 days post
      shower) from air captures in the low-latitude plateau of China produced resting
      spores (azygospores), primary conidia or both spore types. Surprisingly, the
      proportion of mycosed cadavers forming resting spores (P(CFRS)) increased sharply
      within the concentrations (C) of 28-240 conidia mm(-2), retained high levels at
      240-1760, but was zero or extremely low at 0.3-16. The P(CFRS)-C relationship fit
      well the logistic equation P(CFRS) = 0.6774/[1 + exp(3.1229-0.0270C)] (r(2) =
      0.975). This clarified for the first time the dependence of in vivo resting spore
      formation of P. nouryi upon the concentration of infective inoculum. A hypothesis
      is thus proposed that some sort of biochemical signals may exist in the host
      pathogen interaction so that the fungal pathogen perceives the signals for prompt
      response to forthcoming host-density changes by either producing conidia for
      infecting available hosts or forming resting spores for surviving host absence in
      situ.

PMID- 18341581
TI  - A system for the construction of targeted unmarked gene deletions in the genus
      Burkholderia.
AB  - Burkholderia species are extremely multidrug resistant, environmental bacteria
      with extraordinary bioremediation and biocontrol properties. At the same time,
      these bacteria cause serious opportunistic infections in vulnerable patient
      populations while some species can potentially be used as bioweapons. The
      complete DNA sequence of more than 10 Burkholderia genomes provides an
      opportunity to apply functional genomics to a collection of widely adaptable
      environmental bacteria thriving in diverse niches and establishing both symbiotic
      and pathogenic associations with many different organisms. However, extreme
      multidrug resistance hampers genetic manipulations in Burkholderia. We have
      developed and evaluated a mutagenesis system based on the homing endonuclease I
      SceI to construct targeted, non-polar unmarked gene deletions in Burkholderia.
      Using the cystic fibrosis pathogen Burkholderia cenocepacia K56-2 as a model
      strain, we demonstrate this system allows for clean deletions of one or more
      genes within an operon and also the introduction of multiple deletions in the
      same strain. We anticipate this tool will have widespread environmental and
      biomedical applications, facilitating functional genomic studies and construction
      of safe strains for bioremediation and biocontrol, as well as clinical
      applications such as live vaccines for Burkholderia and other Gram-negative
      bacterial species.

PMID- 18341582
TI  - The coordinate regulation of multiple terminal oxidases by the Pseudomonas putida
      ANR global regulator.
AB  - Pseudomonas putida KT2440 contains a branched aerobic respiratory chain with
      multiple terminal oxidases. Their relative proportion varies according to
      environmental conditions. The role of the oxygen-responsive ANR global regulator
      on expression of these terminal oxidases was analysed. During exponential growth
      in a highly aerated complete medium, ANR activated expression of the Cbb3-1
      terminal oxidase (equivalent to Pseudomonas aeruginosa Cbb3-2), but had little
      role on expression of other terminal oxidases. In early stationary phase, or
      under oxygen limitation, inactivation of the anr gene led to increased expression
      of the bo(3)-type cytochrome (Cyo) and cyanide-insensitive (CIO) terminal
      oxidases, and to a much lower expression of Cbb3-1. DNase I footprints identified
      ANR binding sites at the promoters for these oxidases. Their location suggests
      that ANR is a transcriptional activator of Cbb3-1 genes and a repressor of CIO
      genes, consistent with expression data. ANR binding sites at the promoter for Cyo
      genes suggests a complex regulation in combination with other factors. Therefore,
      ANR coordinates expression of Cyo, CIO and Cbb3-1, but does not influence
      cytochrome aa3 and Cbb3-2 terminal oxidases under the conditions analysed.
      Functional assays showed that Cyo has a leading role during aerobic exponential
      growth, while Cbb3-1 becomes very important in stationary phase.

PMID- 18341583
TI  - Differences of heterotrophic 13CO2 assimilation by Pseudomonas knackmussii strain
      B13 and Rhodococcus opacus 1CP and potential impact on biomarker stable isotope
      probing.
AB  - Motivated by the finding that Pseudomonas knackmussii B13 but not Rhodococcus
      opacus 1CP grows in the absence of externally provided CO(2), we investigated the
      assimilation of (13)CO(2) into active cells cultivated with non-labelled glucose
      as sole energy substrate. (13)C found in the bulk biomass indicated a substantial
      but different CO(2) assimilation by Pseudomonas and Rhodococcus, respectively
      (3500 per thousand and 2600 per thousand). Cellular fatty acids were labelled
      from -15 per thousand to 470 per thousand and amino acids from 500 per thousand
      to 24,000 per thousand demonstrating clear differences between various compound
      classes. 'You are what you eat plus 1 per thousand' is therefore only valid for
      the average bulk C without specific isotope signature deviation of the external
      CO(2) or carbonates. Odd-numbered and 10-methyl fatty acids, which are much more
      abundant in Rhodococcus or other Gram-positive bacteria, were up to fivefold
      higher enriched in (13)C relative to the Pseudomonas fatty acids. A high-level
      growth-phase-independent, labelling of the oxaloacetate-derived amino acids
      indicated heterotrophic CO(2) fixation by anaplerotic reactions known to
      replenish the tricarboxylic acid cycle. Although both strains assimilate CO(2)
      via similar general pathways, Rhodococcus depends to a much higher extent on
      carboxylations reactions with external CO(2) owing to the formation of odd
      numbered fatty acids. As a general consequence, heterotrophic fixation of CO(2)
      should be taken into account in investigations of degradation experiments using
      isotope tracer compounds.

PMID- 18341584
TI  - Widespread distribution of a unique marine protistan lineage.
AB  - Unicellular eukaryotes (protists) are key components of marine food webs, yet
      knowledge of their diversity, distributions and respective ecologies is limited.
      We investigated uncultured protists using 18S rRNA gene sequencing, phylogenetic
      analyses, specific fluorescence in situ hybridization (FISH) probes and other
      methods. Because few studies have been conducted in warm water systems, we
      focused on two Atlantic subtropical regions, the Sargasso Sea and the Florida
      Current. Cold temperate waters were also sampled. Gene sequences comprising a
      unique eukaryotic lineage, herein termed 'biliphytes', were identified in most
      samples, whether from high- (30 degrees C) or from low- (5 degrees C) temperature
      waters. Sequences within this uncultured group have previously been retrieved
      from high latitudes. Phylogenetic analyses suggest biliphytes are a sister group
      to the cryptophytes and katablepharids, although the relationship is not
      statistically supported. Bootstrap-supported subclades were delineated but
      coherence was not obvious with respect to geography or physicochemical
      parameters. Unlike results from the initial publication on these organisms
      (therein 'picobiliphytes'), we could not detect a nucleomorph, either visually,
      or by targeted primers. Phycobilin-like fluorescence associated with biliphyte
      specific FISH-probed cells supports the hypothesis that they are photosynthetic.
      Our data indicate the biliphytes are nanoplanktonic in size, averaging 4.1 +/-
      1.0 x 3.5 +/- 0.8 microm (+/-SD) for one probed group, and 3.5 +/- 0.9 x 3.0 +/-
      0.9 microm (+/-SD) for another. We estimate biliphytes contributed 28 (+/-6)% of
      the phytoplanktonic biomass in tropical eddy-influenced surface waters. Given
      their broad thermal and geographic distribution, understanding the role these
      protists play in biogeochemical cycling within different habitats is essential.

PMID- 18341585
TI  - Testing the assumptions of chronosequences in succession.
AB  - Many introductory ecology textbooks illustrate succession, at least in part, by
      using certain classic studies (e.g. sand dunes, ponds/bogs, glacial till, and old
      fields) that substituted space for time (chronosequence) in determining the
      sequences of the succession. Despite past criticisms of this method, there is
      continued, often uncritical, use of chronosequences in current research on topics
      besides succession, including temporal changes in biodiversity, productivity,
      nutrient cycling, etc. To show the problem with chronosequence-based studies in
      general, we review evidence from studies that used non-chronosequence methods
      (such as long-term study of permanent plots, palynology, and stand
      reconstruction) to test the space-for-time substitution in four classic
      succession studies. In several cases, the tests have used the same locations and,
      in one case, the same plots as those in the original studies. We show that
      empirical evidence invalidates the chronosequence-based sequences inferred in
      these classic studies.

PMID- 18341586
TI  - The antibacterial and antifungal properties of trappin-2 (pre-elafin) do not
      depend on its protease inhibitory function.
AB  - Trappin-2 (also known as pre-elafin) is an endogenous inhibitor of neutrophil
      serine proteases and is involved in the control of excess proteolysis, especially
      in inflammatory events, along with the structurally related secretory leucocyte
      proteinase inhibitor. Secretory leucocyte proteinase inhibitor has been shown to
      have antibacterial and antifungal properties, whereas recent data indicate that
      trappin-2 has antimicrobial activity against Pseudomonas aeruginosa and
      Staphylococcus aureus. In the present study, we tested the antibacterial
      properties of trappin-2 towards other respiratory pathogens. We found that
      trappin-2, at concentrations of 5-20 microm, has significant activity against
      Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pneumoniae,
      Branhamella catarrhalis and the pathogenic fungi Aspergillus fumigatus and
      Candida albicans, in addition to P. aeruginosa and S. aureus. A similar
      antimicrobial activity was observed with trappin-2 A62D/M63L, a trappin-2 variant
      that has lost its antiprotease properties, indicating that trappin-2 exerts its
      antibacterial effects through mechanisms independent from its intrinsic
      antiprotease capacity. Furthermore, the antibacterial and antifungal activities
      of trappin-2 were sensitive to NaCl and heparin, demonstrating that its mechanism
      of action is most probably dependent on its cationic nature. This enables trappin
      2 to interact with the membranes of target organisms and disrupt them, as shown
      by our scanning electron microscopy analyses. Thus, trappin-2 not only provides
      an antiprotease shield, but also may play an important role in the innate defense
      of the human lungs and mucosae against pathogenic microorganisms.

PMID- 18341587
TI  - Upregulation of DR5 by proteasome inhibitors potently sensitizes glioma cells to
      TRAIL-induced apoptosis.
AB  - This study was undertaken to explore the potential of new therapeutic approaches
      designed to reactivate cell death pathways in apoptosis-refractory gliomas and to
      characterize the underlying molecular mechanisms of this reactivation. Here we
      investigated the sensitivity of a panel of glioma cell lines (U87, U251, U343,
      U373, MZ-54, and MZ-18) to apoptosis induced by the death receptor ligand tumor
      necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL in combination
      with gamma irradiation, and TRAIL in combination with proteasome inhibitors
      (MG132 and epoxomicin). Analysis of these six glioma cell lines revealed drastic
      differences in their sensitivity to these treatments, with two of the six cell
      lines revealing no significant induction of cell death in response to TRAIL
      alone. Interestingly, the proteasome inhibitors MG132 and epoxomicin were capable
      of potentiating TRAIL-induced apoptosis in TRAIL-sensitive U87 and U251 cells and
      of reactivating apoptosis in TRAIL-resistant U343 and U373 cells. In contrast,
      gamma irradiation had no synergistic effects with TRAIL in the two TRAIL
      resistant cell lines. RNA interference against death receptor 5 (DR5) revealed
      that reactivation of TRAIL-induced apoptosis by proteasome inhibitors depended on
      enhanced transcription and surface expression of DR5. Transient knockdown of the
      transcription factor GADD153/C/EBP homologous protein and application of the
      synthetic c-Jun N-terminal kinase inhibitor SP600125 indicated that enhanced DR5
      expression occurred independently of GADD153/C/EBP homologous protein, but
      required activation of the c-Jun N-terminal kinase/c-Jun signaling pathway. Novel
      therapeutic approaches using TRAIL or agonistic TRAIL receptor antibodies in
      combination with proteasome inhibitors may represent a promising approach to
      reactivate apoptosis in therapy-resistant high-grade gliomas.

PMID- 18341588
TI  - Distinct signaling pathways of microtubule inhibitors--vinblastine and Taxol
      induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent
      mechanisms, respectively.
AB  - Vinblastine and paclitaxel (Taxol) are widely used chemotherapeutic drugs that
      inhibit the normal function of microtubules causing mitotic arrest and cell
      death. Despite these similarities, the signaling pathways that mediate and
      regulate cell death induced by these agents remain incompletely understood. The
      purpose of this study was to directly compare the two drugs in terms of their
      ability to activate components of the c-Jun N-terminal protein kinase (JNK)
      pathway, and to establish the importance of these signaling events in apoptosis
      induced by these agents. We show that both drugs induce mitotic arrest and
      subsequent apoptotic cell death with highly similar kinetics and that both
      activate JNK and induce c-Jun protein and c-jun mRNA expression. Surprisingly,
      vinblastine induced c-Jun phosphorylation and c-jun transcriptional activation,
      although Taxol failed to do so. However, inhibition of JNK or an absence of JNK
      protected against both vinblastine- and Taxol-induced cell death. These results
      suggest that although JNK activation plays an important role in cell death
      induced by both agents, vinblastine and Taxol differ markedly with respect to
      signaling downstream of JNK, with AP-1-dependent and -independent mechanisms,
      respectively. In addition, these results show, contrary to popular belief, that
      JNK activation is not necessarily accompanied by c-Jun activation, and thus c-Jun
      is not an obligate substrate of JNK.

PMID- 18341589
TI  - Structural modeling and mutational analysis of yeast eukaryotic translation
      initiation factor 5A reveal new critical residues and reinforce its involvement
      in protein synthesis.
AB  - Eukaryotic translation initiation factor 5A (eIF5A) is a protein that is highly
      conserved and essential for cell viability. This factor is the only protein known
      to contain the unique and essential amino acid residue hypusine. This work
      focused on the structural and functional characterization of Saccharomyces
      cerevisiae eIF5A. The tertiary structure of yeast eIF5A was modeled based on the
      structure of its Leishmania mexicana homologue and this model was used to predict
      the structural localization of new site-directed and randomly generated
      mutations. Most of the 40 new mutants exhibited phenotypes that resulted from eIF
      5A protein-folding defects. Our data provided evidence that the C-terminal alpha
      helix present in yeast eIF5A is an essential structural element, whereas the
      eIF5A N-terminal 10 amino acid extension not present in archaeal eIF5A homologs,
      is not. Moreover, the mutants containing substitutions at or in the vicinity of
      the hypusine modification site displayed nonviable or temperature-sensitive
      phenotypes and were defective in hypusine modification. Interestingly, two of the
      temperature-sensitive strains produced stable mutant eIF5A proteins--eIF5A(K56A)
      and eIF5A(Q22H,L93F)--and showed defects in protein synthesis at the restrictive
      temperature. Our data revealed important structural features of eIF5A that are
      required for its vital role in cell viability and underscored an essential
      function of eIF5A in the translation step of gene expression.

PMID- 18341590
TI  - Hypoxia-driven proliferation of embryonic neural stem/progenitor cells--role of
      hypoxia-inducible transcription factor-1alpha.
AB  - We recently reported that intermittent hypoxia facilitated the proliferation of
      neural stem/progenitor cells (NPCs) in the subventricule zone and hippocampus in
      vivo. Here, we demonstrate that hypoxia promoted the proliferation of NPCs in
      vitro and that hypoxia-inducible factor (HIF)-1alpha, which is one of the key
      molecules in the response to hypoxia, was critical in this process. NPCs were
      isolated from the rat embryonic mesencephalon (E13.5), and exposed to different
      oxygen concentrations (20% O(2), 10% O(2), and 3% O(2)) for 3 days. The results
      showed that hypoxia, especially 10% O(2), promoted the proliferation of NPCs as
      assayed by bromodeoxyuridine incorporation, neurosphere formation, and
      proliferation index. The level of HIF-1alpha mRNA and protein expression detected
      by RT-PCR and western blot significantly increased in NPCs subjected to 10% O(2).
      To further elucidate the potential role of HIF-1alpha in the proliferation of
      NPCs induced by hypoxia, an adenovirus construct was used to overexpress HIF
      1alpha, and the pSilencer 1.0-U6 plasmid as RNA interference vector targeting HIF
      1alpha mRNA was used to knock down HIF-1alpha. We found that overexpression of
      HIF-1alpha caused the same proliferative effect on NPCs under 20% O(2) as under
      10% O(2). In contrast, knockdown of HIF-1alpha inhibited NPC proliferation
      induced by 10% O(2). These results demonstrated that moderate hypoxia was more
      beneficial to NPC proliferation and that HIF-1alpha was critical in this process.

PMID- 18341591
TI  - Assessment of papillary fibroelastomas with live three-dimensional transthoracic
      echocardiography.
AB  - Seven consecutive patients presenting with typical echocardiographic features of
      papillary fibroelastoma requiring surgery were studied. All patients underwent
      standard two-dimensional (2D) transthoracic echocardiography (TTE) followed by
      live three-dimensional (live 3D) echocardiography with data set storage allowing
      analysis with systematic cropping of the acquired 3D data and volume measurement
      of the lesions. Assessment of papillary fibroelastoma by 2D and live 3D TTE was
      compared to operative findings. The feasibility of live 3D echocardiography in
      this setting was 100%. The quality of images was considered as optimal in three
      patients, good in three patients, and poor in one patient. A typical speckled
      appearance of the tumor was observed in three patients presenting with large
      tumors. The location of the tumor attachment was precisely defined in all but one
      patient, with a clear improvement in spatial assessment with live 3D TTE in three
      patients. Live 3D TTE also improved the operative planning in three patients.
      Live 3D TTE appears to be useful in the assessment of intracardiac tumors as
      small as papillary fibroelastomas, leading to a comprehensive approach of the
      lesion and facilitating the operative planning.

PMID- 18341592
TI  - Cardiovascular risk factor management is poorer in diabetic patients with
      undiagnosed peripheral arterial disease than in those with known coronary heart
      disease or cerebrovascular disease. Results of a nationwide study in tertiary
      diabetes centres.
AB  - AIMS: To assess whether patients with Type 2 diabetes mellitus and unrecognized
      peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI),
      have poorer cardiovascular risk factor management (CVRFs) and receive fewer
      medications than patients previously diagnosed with coronary heart disease (CHD)
      or cerebrovascular disease (CVD). METHODS: In 31 diabetes centres throughout
      Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using
      the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were
      recorded. RESULTS: Forty-one patients had an ABI > 1.30 and were excluded,
      leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened,
      790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no
      CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known
      history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD
      and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density
      lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001)
      and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared
      with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P
      < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet
      agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P <
      0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the
      undiagnosed PAD group was associated with the underutilization of statins.
      CONCLUSIONS: Measurement of ABI detected a significant number of patients with
      PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly
      controlled compared with subjects with CHD and/or CVD.

PMID- 18341593
TI  - Thermoregulatory sudomotor dysfunction and diabetic neuropathy develop in
      parallel in at-risk feet.
AB  - AIMS: To establish the longitudinal relationship of foot complications to
      neuropathy based on a 4-year follow-up of diabetic patients stratified by
      sudomotor dysfunctions. METHODS: One hundred and nineteen Type 2 diabetic
      patients and 36 non-diabetic subjects were initially registered in the
      prospective cohort study. Plantar skin temperature and sympathetic skin response
      (SSR) were used to monitor sympathetic mediated thermoregulation and sudomotor
      function. Peripheral somatic and central autonomic functions were studied using
      clinical, nerve conduction and cardiovascular reflex tests. At enrolment, the
      diabetic patients were classified into one of three groups by the progressive
      stages of sudomotor dysfunction: SSR+ (SSR present; 49 patients), SSR- (SSR
      absent; 41 patients) and at-risk group (SSR absent but with cracked skin
      involving partial thickness of the dermis; 29 patients). RESULTS: The at-risk
      group had 13.4 times (95% confidence interval 1.4-125.7) higher plantar
      ulceration rates than the other two patient groups during the 4 years. Skin
      temperature elevation occurred in parallel with development of foot sweating
      problems. There were no significant differences between the three patient groups
      in the ratios of abnormal heart rate variation, orthostatic test and clinical
      neuropathy score at follow-up. After 4 years of follow-up, nerve conduction
      abnormalities were more frequent in the at-risk and SSR- groups than in the SSR+
      group. CONCLUSIONS: Early deterioration of small sympathetic fibres could not be
      quantified accurately by the clinical, somatic and autonomic tests. Assessing
      skin integrity and sudomotor function in at-risk individuals identifies early
      peripheral sympathetic neuropathy, even if the patients have no overt clinical
      symptoms.

PMID- 18341594
TI  - The development of personal models of diabetes in the first 2 years after
      diagnosis: a prospective longitudinal study.
AB  - AIMS: Personal models of diabetes comprise beliefs about symptoms, treatment
      effectiveness, consequences and emotional responses to possible future
      complications. They are associated with, and influence, self-care behaviour.
      Little work has examined potential influences on the development and maintenance
      of personal models. The aims of this study were: (i) to assess changes in
      personal models over 2 years from diagnosis of diabetes; and (ii) to examine the
      relative contributions of health threat communication (at diagnosis, since
      diagnosis, during follow-up care) and personality to personal models of diabetes
      2 years post-diagnosis. METHODS: Newly diagnosed patients were interviewed at
      diagnosis (< 3 months; time 1) and 6 months (time 2), 1 year (time 3) and 2 years
      (time 4) after diagnosis. Data were available for 158 patients at time 1 (32 Type
      1 patients and 126 Type 2 patients), 147 at time 2, 142 at time 3 and 138 at time
      4. RESULTS: Perceptions of symptoms, consequences, course and control of diabetes
      remained stable over time. Emotional responses decreased and illness coherence
      (perceived understanding) increased over time. Health threat communication was a
      stronger predictor of personal models than personality. Emotional responses to
      diabetes 2 years after diagnosis were predicted by perceptions of a threatening
      health message (at diagnosis 18%, at follow-up 5%). Health threat communication
      predicted perceptions of serious consequences (at diagnosis 5%, at follow-up 9%).
      Perceptions of a reassuring message during follow-up were related to beliefs of
      treatment effectiveness (26%). CONCLUSIONS: The communication of information and
      the way it is perceived is an important determinant of the patient's view of
      their diabetes. The initial effects of the education process at diagnosis
      persisted 2 years after diagnosis.

PMID- 18341596
TI  - Comparison of vildagliptin and acarbose monotherapy in patients with Type 2
      diabetes: a 24-week, double-blind, randomized trial.
AB  - AIMS: To compare the efficacy and tolerability of the dipeptidyl peptidase-4
      inhibitor, vildagliptin, with the alpha glucosidase inhibitor, acarbose, in drug
      naive patients with Type 2 diabetes. METHODS: This multi-centre, randomized,
      double-blind, parallel-arm study compared the efficacy and tolerability of
      vildagliptin (100 mg daily, given as 50 mg twice daily, n = 441) and acarbose (up
      to 300 mg daily, given as three equally divided doses, n = 220) during 24-week
      treatment in drug-naive patients with Type 2 diabetes. RESULTS: Monotherapy with
      vildagliptin or acarbose decreased glycated haemoglobin (HbA(1c)) (baseline
      approximately 8.6%) to a similar extent during 24-week treatment. The adjusted
      mean change from baseline to end-point (AMDelta) in HbA(1c) was -1.4 +/- 0.1% and
      -1.3 +/- 0.1% in patients receiving vildagliptin and acarbose, respectively,
      meeting the statistical criterion for non-inferiority (upper limit of 95%
      confidence interval for between-treatment difference < or = 0.4%). The decrease
      in fasting plasma glucose was similar with acarbose (-1.5 +/- 0.2 mmol/l) and
      vildagliptin (-1.2 +/- 0.1 mmol/l). Body weight did not change in vildagliptin
      treated patients (-0.4 +/- 0.1 kg) but decreased in acarbose-treated patients (
      1.7 +/- 0.2 kg, P < 0.001 vs. vildagliptin). The proportion of patients
      experiencing any adverse event (AE) was 35% vs. 51% in patients receiving
      vildagliptin or acarbose, respectively; gastrointestinal AEs were significantly
      more frequent with acarbose (25.5%) than vildagliptin (12.3%, P < 0.001). No
      hypoglycaemia was reported for either group. CONCLUSIONS: Vildagliptin is
      effective and well tolerated in patients with Type 2 diabetes, demonstrating
      similar glycaemic reductions to acarbose, but with better tolerability.

PMID- 18341597
TI  - Chronic renal dysfunction following liver transplantation.
AB  - With most of the immunosuppressive protocols consisting of calcineurin inhibitors
      (CI), nephrotoxicity has become a major long-term complication often compromising
      outcome. In a single-center retrospective study, we reviewed 1173 liver
      transplantations to identify variables indicative for the occurrence of chronic
      renal dysfunction (CRD) (defined as > or = 1 episode of serum creatinine increase
      > or = 1.8 mg/dL > or = 2 wk). Chronic renal dysfunction was found in 137 (11.7%)
      of all transplants [82 (7%) early (after 3-12 months), 55 (4.7%) late-onset (> 12
      months)]. Compared to 5-/10-yr survival rates in non-CRD transplants (84/74%)
      survival was significantly decreased in early (66/46%), but unchanged in late
      onset CRD (98/86%). Rates of alcoholic cirrhosis and prior renal dysfunction were
      significantly increased in patients with CRD. In a multivariate logistic
      regression analysis, only cyclosporine A (CyA) as immunosuppression remained an
      independent risk factor. No correlations to age, gender,
      rejection/retransplantation or diabetes were found. Surprisingly, renal function
      (creatinine) showed no difference between patients on CI monotherapy (FK/CyA)
      compared to those who had mycophenolate mofetil (MMF) added. In liver
      transplantation, early onset CRD significantly compromises survival. CyA-based
      immunosuppression appears to have a stronger impact than FK. The fact that
      patients with long-term severe chronic renal dysfunction failed to improve under
      MMF rescue therapy emphasizes the importance of new diagnostic strategies to
      earlier identify at-risk patients.

PMID- 18341598
TI  - Calcium-binding protein 1 of Entamoeba histolytica transiently associates with
      phagocytic cups in a calcium-independent manner.
AB  - EhCaBP1, a calcium-binding protein of the parasite Entamoeba histolytica, is
      known to participate in cellular processes involving actin filaments. This may be
      due to its direct interaction with actin. In order to understand the kinetics of
      EhCaBP1 in such processes, its movement was studied in living cells expressing
      GFP-EhCaBP1. The results showed that EhCaBP1 accumulated at phagocytic cups and
      pseudopods transiently. The time taken for appearance and disappearance of
      EhCaBP1 was found to be around 12 s. Site-directed mutagenesis was used to
      generate an EhCaBP1 mutant with reduced Ca(2+)- and G-actin binding ability
      without any defect in its ability to bind F-actin. The overexpression of this
      mutant EhCaBP1 in the E. histolytica trophozoites resulted in the impairment of
      erythrophagocytosis, uptake of bacterial cells, killing of target cells but not
      fluid-phase pinocytosis. However, the mutant protein was still found to
      transiently localize with F-actin at the phagocytic cups and pseudopods. The
      mutant protein displayed reduced ability to activate endogenous kinase(s)
      suggesting that phagosome formation may require Ca(2+)-EhCaBP1 transducing
      downstream signalling but initiation of phagocytosis may be independent of its
      intrinsic ability to bind Ca(2+). The results suggest a dynamic association of
      EhCaBP1 with F-actin-mediated processes.

PMID- 18341599
TI  - Periodontal disease definition may determine the association between
      periodontitis and pregnancy outcomes.
AB  - AIM: The aim of this secondary analysis is to explore whether the application of
      different definition criteria of periodontitis, used in other similar studies,
      has an influence on the significance of the association between periodontitis and
      prematurity or low birth weight. MATERIAL AND METHODS: Fourteen periodontitis
      definitions and more than 50 periodontal disease continuous measurements, found
      in 23 published studies, were applied to a cohort study that included 1296
      pregnant women. The associations with adverse pregnancy outcomes were analysed
      using logistic regression analysis. RESULTS: Six of the 14 tested definitions of
      periodontitis resulted in statistically significant adjusted odds ratios (ORs)
      for some of the adverse pregnancy outcomes, while no significance was found for
      the other eight case definitions. Out of more than 50 periodontal continuous
      measurements tested, only 17 demonstrated statistically significant ORs.
      CONCLUSIONS: Our results support the hypothesis that the significance of the
      association between periodontal disease and pregnancy outcomes may be determined
      by the periodontal disease definition or measurement used.

PMID- 18341600
TI  - Effect of ultrasonic debridement using a chlorhexidine irrigant on circulating
      levels of lipopolysaccharides and interleukin-6.
AB  - AIM: Transient bacteraemia and endotoxaemia, and elevated levels of systemic
      cytokines have been reported following subgingival debridement. This study aimed
      to investigate the effect of chlorhexidine (CHX) solution on circulating levels
      of lipopolysaccharide (LPS) and interleukin-6 (IL-6) when used as an irrigant
      during ultrasonic debridement in patients with periodontitis. MATERIAL AND
      METHODS: Eighteen patients with moderate to advanced chronic periodontitis were
      treated in a split-mouth, crossover, single-masked study. Irrigation with 0.02%
      CHX solution or water was used during treatment of two ipsilateral quadrants on
      two separate occasions 7 days apart, randomized as to order. Peripheral blood
      samples were collected for circulating levels of LPS and IL-6 at baseline, 5 and
      120 min. after instrumentation commenced. RESULTS: Median concentrations of LPS
      were elevated from baseline to 5 min. into treatment with both CHX and control
      irrigant (p<0.05). Median levels of IL-6 increased with both treatments from
      baseline to 120 min. (p<0.001): CHX, 0.81-1.85 pg/ml; control, 0.78-1.78 EU/ml.
      CONCLUSIONS: Ultrasonic instrumentation in patients with moderate to advanced
      periodontitis increases circulating levels of LPS after 5 min. and IL-6 120 min.
      after commencement of treatment, and is not affected by using 0.02% CHX as an
      irrigant instead of water.

PMID- 18341601
TI  - Clinical outcomes after treatment of intra-bony defects with an EMD/synthetic
      bone graft or EMD alone: a multicentre randomized-controlled clinical trial.
AB  - OBJECTIVES: Comparison of the outcomes of a combination of an enamel matrix
      derivative and a synthetic bone graft (EMD/SBC) with EMD alone in wide intra-bony
      defects. MATERIAL AND METHODS: Seventy-three patients with chronic periodontitis
      were recruited in five centres in Germany. All patients had one wide intra-bony
      defect of >/=4 mm. Surgical procedures involved microsurgical technique and the
      modified papilla preservation flap. After debridement, defects were randomly
      assigned to EMD/SBC (test) or EMD (control). Assessments at baseline and after 6
      months included bone sounding, attachment levels, probing pocket depths, bleeding
      on probing and recessions. Early wound-healing, adverse effects and patients'
      perceptions were also recorded. RESULTS: Both treatment modalities led to
      significant clinical improvements. Change in bone fill 6 months after surgery was
      2.0 mm (+/- 2.1) in the test group and 2.1 mm (+/- 1.2) in the control group. A
      gain in clinical attachment of 1.3 mm (+/- 1.8) in the test group and 1.8 mm (+/-
      1.6) in the control group was observed. One week after surgery, primary closure
      was maintained in 95% of the test sites and 100% of the control sites. No
      differences in patients' perceptions were found. CONCLUSION: The results of the
      present study showed similar clinical outcomes following both treatment
      modalities.

PMID- 18341602
TI  - A double-blind randomized clinical evaluation of enamel matrix derivative
      proteins for the treatment of proximal class-II furcation involvements.
AB  - OBJECTIVE: The aim of the present randomized, double-blind study was to evaluate
      the clinical response of proximal furcations treated with enamel matrix
      derivative proteins (EMD). MATERIAL AND METHODS: Fifteen patients, each with a
      pair of contralateral class-II proximal furcation involvements, presenting
      probing depths (PDs) >/=5 mm and bleeding on probing (BOP) were selected. The
      patients were randomly assigned to: control group (n=15) - open flap debridement
      (OFD)+24% ethylenediaminetetraacetic acid (EDTA) conditioning; test group (n=15) 
      OFD+24% EDTA conditioning+EMD application. Plaque index (PI), BOP, PD, gingival
      margin position (GMP), relative vertical and horizontal clinical attachment level
      (RVCAL and RHCAL), vertical and horizontal bone level (VBL and HBL) and furcation
      closure were evaluated immediately before and 2, 4 and 6 months after the
      surgeries. RESULTS: At 6 months, the RVCAL gains of the control and test group
      were 0.39 +/- 1.00 and 0.54 +/- 0.95 mm, while the RHCAL gains were 1.21 +/- 2.28
      and 1.36 +/- 1.26 mm (p>0.05). The VBL and HBL gains of the control group were
      1.04 +/- 1.12 and 1.00 +/- 1.79 mm, and 0.82 +/- 1.82 and 1.17 +/- 1.38 mm for
      the test group (p>0.05). In addition, a statistical difference was observed in
      the number of the remaining class-II furcations between the test and control
      groups (p<0.05) in this period. CONCLUSION: It may be concluded that the use of
      EMD in proximal furcations did not promote a superior reduction in PD or a gain
      in clinical and osseous attachment levels, but resulted in a higher rate of class
      II to class-I furcation conversion.

PMID- 18341603
TI  - Association between alcohol consumption and dental health.
AB  - OBJECTIVES: To study the association of alcohol consumption with dental health in
      a sample from the County of Stockholm. MATERIAL AND METHODS: In a longitudinal
      investigation, 513 individuals were examined in 1970 and 1990. Clinical and
      radiographic examinations were performed as well as an interview including
      questions on alcohol consumption. The clinical investigation consisted of the
      registration of the number of remaining teeth, dental restorations, caries and
      periodontal conditions. The marginal bone level and longitudinal bone loss were
      determined by assessments on the proximal surfaces of all measurable teeth on the
      radiographs. Stepwise multiple regression analyses were adopted to calculate the
      partial correlations between alcohol consumption and the investigated
      odontological variables. RESULTS: The group of subjects with the highest alcohol
      consumption (>5 cl pure alcohol per day) had more tooth surfaces with caries,
      more calculus and more teeth with apical lesions compared with those who reported
      an alcohol consumption </=5 cl of pure alcohol per day. Alcohol consumption was
      not associated with periodontal disease. CONCLUSION: The observations do not
      support any association between alcohol consumption and periodontal disease.
      However, individuals with high alcohol consumption had significantly more teeth
      with decayed surfaces and apical lesions indicating that lifestyle-related
      factors may influence dental health.

PMID- 18341604
TI  - Factors influencing the trailing endpoint observed in Candida albicans
      susceptibility testing using the CLSI procedure.
AB  - The trailing endpoint phenotype observed during testing of Candida albicans
      susceptibility to azoles according to the CLSI procedure is defined as a
      difference in MIC depending on whether the result is obtained after 24 or 48 h.
      This study investigated whether intrinsic differences between the EUCAST and CLSI
      methods could explain trailing growth. The glucose concentration in the medium
      and the shape of the microtitre plate wells were both found to be involved. In
      order to reduce the incidence of trailing growth according to the CLSI procedure,
      the use of higher glucose concentrations and flat-bottomed microtitre plates
      could be valuable improvements.

PMID- 18341605
TI  - Mental retardation in a girl with a subtelomeric deletion on chromosome 20q and
      complete deletion of the myelin transcription factor 1 gene (MYT1).
AB  - A great number of syndromes and inborn errors of metabolism associated with
      impaired development have been observed, but the aetiology of mental retardation
      remains unclear in a considerable proportion of cases. Here, we present the
      clinical and molecular data from a patient with a new de novo subtelomeric
      deletion on chromosome 20 [46,XX.ish del(20)(qter-)]. For further refinement,
      bacterial artificial chromosome clones are used. The deletion spans exactly two
      genes called MYT1 and PCMTD2. Both genes play an important role in myelination
      and regulating neural differentiation. Loss of these two genes seems to be
      responsible for the severe mental retardation and mild facial dysmorphic features
      in our young patient. It might show the phenotypic picture of this specified
      deletion.

PMID- 18341606
TI  - Huntington disease-like 2: the first patient with apparent European ancestry.
AB  - Huntington disease-like 2 (HDL2) is a rare autosomal dominant disorder of the
      nervous system, apparently indistinguishable from Huntington disease (HD). HDL2
      is caused by the expansion above 40 CTG/CAG repeats, in a variably spliced exon
      of the junctophilin-3 gene, on chromosome 16q24.3. All patients described so far
      have been of African ancestry. A clinical evaluation, including the Unified
      Huntington's Disease Rating Scale, and brain Magnetic resonance imaging were
      achieved in a 48-year-old Brazilian man of apparent European extraction, and
      presenting a picture very suggestive of HD. Gene mutation analysis (HD, HDL1,
      HDL2, dentatorubralpallidoluysian atrophy and spinocerebellar ataxia 17) was
      performed. After exclusion of the HD mutation and other HDL disorders, we
      identified an expansion of 47 CTG/CAG at the HDL2 locus. To clarify the origin of
      the mutation and estimate the patient's ancestry, we performed haplotype studies
      and used the insertion/deletion polymorphisms method. Despite the fact that this
      patient had an estimated likelihood of 97.4% of being of European ancestry, the
      haplotype containing the expanded allele has been found only in Africans. Thus,
      this is the first HDL2 case reported in a patient with an apparent European
      ancestry, although bearing an African HDL2 haplotype. This work stresses the
      importance of performing the diagnosis of HDL2 in HD-like patients of various
      ethnicities, and particularly in highly mixed populations.

PMID- 18341607
TI  - Family history as a predictor of uptake of cancer preventive procedures by women
      with a BRCA1 or BRCA2 mutation.
AB  - Women with a BRCA1 or BRCA2 mutation are at an elevated risk of developing breast
      and ovarian cancer; however, it is unclear to what extent family history
      influences the uptake of cancer prevention options. Women with a BRCA1/2 mutation
      completed a follow-up questionnaire that assessed uptake of cancer preventive
      options. The pedigree of each woman was reviewed, and information was recorded on
      cancers diagnosed in relatives. Five hundred and seventeen women were included in
      the study. Women with a sister with breast cancer were more likely to have a
      prophylactic mastectomy than those without a sister with breast cancer [odds
      ratios (OR) = 2.4, p = 0.003]. Uptake of prophylactic mastectomy was
      significantly lower in women with a mother with ovarian cancer compared with
      those whose mother did not have ovarian cancer (OR = 0.4, p = 0.01). Having a
      mother or sister with ovarian cancer significantly predicted the uptake of
      prophylactic oophorectomy (OR = 1.6, p = 0.04). Women with a BRCA2 mutation were
      less likely to have a prophylactic oophorectomy than those with a BRCA1 mutation
      (OR = 0.49, p = 0.0004). Among women with a BRCA1 or BRCA2 mutation, family
      history predicts the uptake of prophylactic mastectomy and prophylactic
      oophorectomy.

PMID- 18341608
TI  - Inclusion body myopathy, Paget's disease of the bone and frontotemporal dementia:
      recurrence of the VCP R155H mutation in an Italian family and implications for
      genetic counselling.
AB  - The acronym IBMPFD denotes a syndrome including inclusion body myopathy, Paget's
      disease of the bone (PDB) and frontotemporal dementia (FTD) as cardinal features,
      which is caused by missense mutations in the VCP gene. We studied the clinical
      characteristics and the histopathological features in two siblings and their
      mother who presented with adult-onset myopathy and presenile, rapidly progressive
      FTD. One sibling also showed PDB. Light and electron microscopy performed on
      muscle biopsies demonstrated degenerative changes with inclusion bodies and
      abnormal aggregates. Mutation analysis of the VCP gene on affected siblings
      revealed a heterozygous missense mutation (R155H) in a hot spot. This is the
      first Italian family with multiple individuals diagnosed as having IBMPFD and
      carrying the recurrent R155H mutation. The implications for genetic counselling
      were also discussed, with regard to the procedures that may be offered to
      families suffering from a multisystem disorder with high risk of cognitive
      decline.

PMID- 18341609
TI  - High mobility group box 1 and adenosine are both released by endothelial cells
      during hypothermic preservation.
AB  - Hypothermic preservation of solid allografts causes profound damage of vascular
      endothelial cells. This, in turn, might activate innate immunity. In the present
      study we employed an in vitro model to study to what extent supernatants of
      damaged endothelial cells are able to activate innate immunity and to study the
      nature of these signals. The expression of high mobility group box 1 (HMGB1) and
      adhesion molecules on human umbilical vein endothelial cell was studied by
      immunofluorescence, fluorescence activated cell sorter and Western blotting.
      Cytokine production was performed by enzyme-linked immunosorbent assay. HMGB1
      expression was lost completely in endothelial cells after hypothermic
      preservation. This was associated with cell damage as it occurred only in
      untreated endothelial cell but not in cells rendered resistant to hypothermia
      mediated damage by dopamine treatment. Only supernatants from hypothermia
      susceptible cells up-regulated the expression of interleukin (IL)-8 and adhesion
      molecules in cultured endothelial cells in an HMGB1-dependent manner. In whole
      blood assays, both supernatants of hypothermia susceptible and resistant cells
      inhibited tumour necrosis factor (TNF)-alpha production concomitantly with an
      increased IL-10 secretion. The activity of the supernatants was already found
      after 6 h of hypothermic preservation, and paralleled the decrease in
      intracellular adenosine triphosphate (ATP) levels. Modulation of TNF-alpha and IL
      10 production by these supernatants was abrogated completely by prior treatment
      with adenosine deaminase and was similar to the response of an A2R agonist. Our
      study demonstrates that both HMGB1 and adenosine are released during hypothermic
      preservation. While release of HMGB1 is caused by cell damage, release of
      adenosine seems to be related to ATP hydrolysis, occurring in both susceptible
      and resistant cells.

PMID- 18341610
TI  - Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a
      mouse model of B cell lymphoma.
AB  - Regulatory T cells (T(regs)) may inhibit immunity against cancer. Induction and
      expansion of T(regs) in the immunosuppressive microenvironment created by a
      growing tumour appear to be one of the mechanisms by which it can evade host
      defence. We studied the impact of CD25+ T(regs) in a B cell lymphoma model in
      which Rag2-/- mice received adoptive transfer of wild-type spleen cells with or
      without CD25+ cells, and concurrently subcutaneous inoculation of the B cell
      lymphoma cell line A20. We also examined the effect of engaging the
      glucocorticoid-induced tumour necrosis factor receptor (GITR) - an approach
      reported previously to abrogate the suppressive effects of T(regs). Mice that
      received spleen cells depleted of CD25+ T(regs) showed significantly slower
      tumour growth and increased survival compared with mice that received unsorted
      spleen cells. The T(reg)-depleted group also had significantly more CD8+ T cells
      infiltrating the tumours and higher levels of serum immunoglobulin G subclasses.
      The anti-GITR treatment had no significant effect on tumour growth, survival or
      immunoglobulin production. In the CD25-depleted group four of 10 mice developed
      clinical signs of autoimmunity, in contrast to none in the non-depleted group.
      Forkhead box P3+ T cells were found in tumour-draining lymph nodes in mice in the
      CD25-depleted group, suggesting an in vivo induction or expansion of rare
      transferred donor T(regs). Thus, our study showed that removal of CD25+ T(regs)
      enhanced anti-tumour immunity against local growth of a B cell lymphoma and that
      induction or expansion of T(regs) could be one mechanism by which the growing
      tumour evades immune surveillance.

PMID- 18341611
TI  - Reduced arthritis in MIF deficient mice is associated with reduced T cell
      activation: down-regulation of ERK MAP kinase phosphorylation.
AB  - Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory
      cytokine with many cellular targets in rheumatoid arthritis (RA). MIF has been
      reported to activate cells via mitogen-activated protein kinase and
      serine/threonine kinase (AKT or protein kinase B)-dependent signal transduction
      pathways. Its contribution to T cell activation and signalling in RA is not
      known. Using MIF -/- mice and a T cell-mediated model of RA, antigen-induced
      arthritis, we investigated the role of MIF in T cell activation and signalling.
      Arthritis severity was significantly reduced in MIF -/- mice compared with
      wildtype mice. This reduction was associated with decreased T cell activation
      parameters including footpad delayed type hypersensitivity, antigen-induced
      splenocyte proliferation and cytokine production. Splenocyte proliferation
      required extracellular signal-regulated kinase (ERK)1/2 phosphorylation, and
      decreased T cell activation in MIF -/- mice was associated with decreased
      phosphorylation of ERK1/2 but not AKT. Collectively, these data suggest that MIF
      promotes antigen-specific immune responses via regulation of ERK phosphorylation
      in T cells.

PMID- 18341612
TI  - The value of serum neopterin, interferon-gamma levels and interleukin-12B
      polymorphisms in predicting acute renal allograft rejection.
AB  - Acute rejection remains a poor predictor of graft outcome. In this study, we
      measured serum levels of interferon (IFN)-gamma and neopterin by enzyme-linked
      immunosorbent assay and a single nucleotide polymorphism (SNP) within the 3'
      untranslated region of the interleukin (IL)-12 B gene (1188 A/C) to determine
      whether either of these factors could predict acute rejection in renal
      transplantation. Significantly higher early post-transplant neopterin levels
      (days 5-7; 35.7 versus 19.9 nmol/l) were observed in recipients who subsequently
      rejected their grafts. Post-transplant neopterin levels showed a strong positive
      correlation with 1-month creatinine levels (Spearman's correlation 0.62, P <
      0.001), suggesting macrophage activation early after transplantation.
      Pretransplant neopterin and IFN-gamma levels and the IL-12B gene SNP did not
      predict acute rejection in this small retrospective study. The ability to predict
      acute rejection non-invasively early after transplantation could lead to
      individual tailoring of immunosuppressive regimens and perhaps lead eventually to
      longer graft survival.

PMID- 18341613
TI  - Two-dimensional gel electrophoresis analysis in simultaneous influenza pneumonia
      and bacterial infection in mice.
AB  - Severe pneumonia is found in simultaneous influenza pneumonia and bacterial
      infection, and suggests a relationship with immunological mechanisms. Here, we
      performed two-dimensional gel electrophoresis to detect immunological molecules
      related to the fulminant pneumonia caused by influenza virus and Streptococcus
      pneumoniae co-infection in mice. We found two spots that were expressed strongly
      in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly
      infected mouse lungs. The spots were analysed by mass spectrometry, and
      identified as alpha-1 anti-trypsin (A1AT), known as an anti-protease for
      neutrophil-derived proteolytic enzymes, and creatine kinase, which reflects a
      greater degree of lung damage and cell death. A1AT expression was increased
      significantly, and proteolytic enzymes from neutrophils, such as neutrophil
      elastase, myeloperoxidase and lysozyme, were also secreted abundantly in
      influenza virus and S. pneumoniae co-infected lungs compared with S. pneumoniae
      or influenza virus singly infected lungs. These data suggest that A1AT may play a
      central role as a molecule with broad anti-inflammatory properties, and
      regulation of the neutrophil-mediated severe lung inflammation is important in
      the pathogenesis of co-infection with influenza virus and bacteria.

PMID- 18341614
TI  - Atorvastatin does not alter serum levels of sCD95 and sCD95L in multiple
      sclerosis.
AB  - Elimination of autoreactive T cells by apoptosis is critical for restricting
      immune responses to self-antigens. An errant lytic interaction between the CD95
      death receptor and its ligand CD95L is presumed to be involved in the
      pathogenesis of multiple sclerosis (MS). Statins are promising agents for the
      treatment of MS and were shown to modulate levels of soluble death receptors.
      Here, we evaluated the in vivo effects by interferon (IFN)-beta and atorvastatin
      on soluble CD95 (sCD95) and sCD95L in serum of patients with MS. Concentrations
      of sCD95 and sCD95L did not show any differences between MS and healthy control
      subjects. In patients with MS, treatment with IFN-beta increased serum levels of
      sCD95 and sCD95L significantly (P < 0.01 and P < 0.05 respectively). Addition of
      atorvastatin to IFN-beta did not alter serum levels of sCD95 and sCD95L
      significantly. Our study suggests that atorvastatin does not affect IFN-beta
      induced increases of the soluble death receptors in the serum of patients with
      MS.

PMID- 18341615
TI  - The tumour suppressor gene p53 modulates the severity of antigen-induced
      arthritis and the systemic immune response.
AB  - p53 is a transcription factor with a well-described role in the induction of
      apoptosis and cell cycle arrest as part of a protective response to a variety of
      stressful stimuli. Expansion of inflamed tissue in rheumatoid arthritis has been
      related to the loss of functioning p53, and the severity of collagen-induced
      arthritis is increased in p53-/- mice. Our objective was to assess the role of
      p53 in a model of adaptive immunity, antigen-induced arthritis (AIA). AIA was
      induced in p53-/- and wild-type mice by priming with methylated bovine serum
      albumin followed by intra-articular challenge. Severity of arthritis was assessed
      using a standardized scoring system and synovial apoptosis was detected by TdT
      mediated biotin-dUTP nick-end labelling. Splenocyte proliferation was measured by
      [H(3)] incorporation and interferon (IFN)-gamma release. Splenocyte viability was
      assessed using Titreglow. Splenic T cell activation status was assessed by flow
      cytometry. Serum cytokines were measured using enzyme-linked immunosorbent assay.
      Increased severity of AIA in p53-/- mice was associated with decreased synovial
      apoptosis and with increased delayed-type hypersensitivity response, increased
      mitogen and antigen-induced splenocyte proliferation and increased IFN-gamma
      release in p53-/- mice compared with wild-type mice. Antigen-specific
      immunoglobulin responses were equivalent in both groups. Splenocyte viability was
      increased in p53-/- mice but T cell apoptosis was equivalent. T cell activation
      markers were increased in p53-/- mice compared with wild-type mice.
      Lipopolysaccharide-induced tumour necrosis factor release was increased in p53-/-
      mice with a trend to increased interleukin-6 in p53-/- mice compared with
      littermates. p53 is involved in the modulation of adaptive and innate immune
      responses relevant to arthritis models and is also involved in the modulation of
      severity of AIA by both cell-cycle dependent and cell-cycle-independent
      mechanisms.

PMID- 18341616
TI  - Monitoring non-immediate allergic reactions to iodine contrast media.
AB  - Non-immediate reactions to iodine contrast media (ICM) affect 2-5% of patients
      receiving these agents. We studied the immunological mechanisms involved in
      patients with a confirmed non-immediate reaction, maculopapular exanthema, after
      administration of ICM. The diagnosis was carried out by skin testing or drug
      provocation test. The immunological study was performed in sequential peripheral
      blood mononuclear cells taken from the onset of the reaction by flow cytometry
      and in skin biopsy by immunohistochemistry, with specific recognition by the
      lymphocyte transformation test (LTT) with different ICM. Flow cytometry showed an
      increase in the different activation markers [CD69, CD25 and human leucocyte
      antigen D-related (HLA-DR)] and the skin homing receptor [cutaneous lymphocyte
      associated antigen (CLA)] in CD4 lymphocytes, whereas perforin was higher in the
      CD8 lymphocytes. The skin biopsy showed a perivascular mononuclear infiltrate
      composed of CD4 lymphocytes, expressing CD25, HLA-DR and CLA, with eosinophils.
      Intradermal skin tests and the LTT were positive to several ICM, including the
      culprit agent in four and three patients, respectively, with negative results in
      all 10 tolerant controls. We showed that a specific immunological mechanism was
      implicated in patients with non-immediate reactions to ICM. Moreover, the
      positive results in skin tests and lymphocyte proliferation tests indicated that
      an important cross-reactivity exists.

PMID- 18341617
TI  - A novel, helminth-derived immunostimulant enhances human recall responses to
      hepatitis C virus and tetanus toxoid and is dependent on CD56+ cells for its
      action.
AB  - We have described previously an immunostimulant derived from Onchocerca volvulus,
      the helminth parasite that causes onchocerciasis. Recombinant O. volvulus
      activation-associated secreted protein-1 (rOv-ASP-1) was a potent adjuvant for
      antibody and cellular responses to protein, polypeptide and small peptide
      antigens. Our aims were to determine whether rOv-ASP-1 is immunostimulatory for
      human peripheral blood mononuclear cells (PBMC) and, if so, whether it could
      augment cellular responses against human pathogen antigens in vitro. Cytokines
      from rOv-ASP-1-stimulated human PBMC were measured by a fluorescence activated
      cell sorter-based multiplex assay. Recall responses of normal healthy donor (NHD)
      and chronic hepatitis C virus (c-HCV)-infected patient PBMC to tetanus toxoid
      (TT) or HCV core (HCVco) antigen, respectively, were measured by interferon-gamma
      enzyme-linked immunospot assays. Interferon-gamma was the predominant cytokine
      induced by rOv-ASP-1. 77.3% of NHD anti-TT and 88.9% of c-HCV anti-HCVco
      responses were enhanced by rOv-ASP-1. The immunostimulant effect was dependent
      upon contact between CD56+ and CD56- fractions of PBMC. We have described a
      helminth-derived protein that can act as an immunostimulant for human recall
      responses in vitro to TT and, perhaps more importantly, HCV antigens in patients
      with chronic HCV infection. Our longer-term goal would be to boost anti-viral
      responses in chronic infections such as HCV.

PMID- 18341618
TI  - Rapid subcutaneous immunoglobulin administration every second week results in
      high and stable serum immunoglobulin G levels in patients with primary antibody
      deficiencies.
AB  - Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy
      in patients with primary antibody deficiences (PAD) is being applied
      increasingly. However, only a few published pharmacokinetic studies are available
      for this route of administration. Therefore, the pharmacokinetics of a 16%
      immunoglobulin G (IgG) preparation intended for subcutaneous use were
      investigated in patients with common variable immunodeficiency and X-linked
      agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to
      12 adult patients every 14 days for 24 weeks (total of 144 infusions).
      Pharmacokinetic parameters were determined based on serum IgG trough levels and
      antibody levels against tetanus. The median half-life of the total serum IgG and
      for the tetanus antibodies was 40.6 and 23.3 days respectively. Median in vivo
      recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively.
      Median, preinfusion serum IgG trough levels per patient were high without major
      variations between infusions and ranged from 7.24 to 7.86 g/l. Safety, in terms
      of adverse events including systemic adverse reactions and local tissue reactions
      at infusions sites, was monitored throughout the study. Six mild, local tissue
      reactions were observed during the study in one patient. No systemic adverse
      reactions related to the study drug were observed and no serious other adverse
      event occurred during the study. It is concluded that the bi-weekly SCIG therapy
      was well tolerated in the study and that it results in high and stable serum IgG
      levels, offering an alternative therapy regimen to patients suffering from PAD.

PMID- 18341619
TI  - Combined effect of tumour necrosis factor-alpha and interleukin-13 polymorphisms
      on bronchial hyperresponsiveness in Korean children with asthma.
AB  - BACKGROUND: TNF-alpha and IL-13, two pivotal pro-inflammatory cytokines, are
      increased in asthmatic airways and may be linked to asthma susceptibility and/or
      bronchial hyperresponsiveness (BHR). OBJECTIVE: We investigated the association
      between the TNF-alpha-308G/A polymorphism and asthma susceptibility or asthma
      related phenotypes in Korean children with asthma, and tested for a combined
      effect with IL-13 polymorphisms. METHODS: Asthmatic children (n=719) and non
      atopic healthy control children (n=243) were evaluated for asthma phenotypes
      including total serum IgE and BHR to methacholine. Genotypes were determined by
      PCR-restriction fragment length polymorphism analysis. RESULTS: The allele
      frequency of TNF-alpha-308A in asthmatics (14.1%) was higher than that in control
      children [8.7%, odds ratio (OR) 1.72, 95% confidence interval (CI) 1.05-2.82].
      Significantly lower PC(20) values were found in asthmatic children carrying one
      or two copies of the TNF-alpha risk allele (-308A) vs. those homozygous for the
      common allele (P=0.026). Combined analysis revealed that atopic asthmatic
      children co-inherited the risk alleles of TNF-alpha-308G/A and IL-13 +2044G/A
      more frequently than control children (aOR 1.91, 95% CI 1.00-3.65), and asthmatic
      children co-inheriting both risk alleles had significantly lower PC(20) values
      vs. asthmatic children homozygous for the common alleles (P=0.024). CONCLUSION:
      The TNF-alpha promoter polymorphism (-308G/A) may be associated with asthma
      susceptibility and BHR in Korean children with asthma. In addition, there appears
      to be a synergistic effect between the TNF-alpha promoter polymorphism and an IL
      13 coding region polymorphism in terms of asthma susceptibility and BHR in this
      population.

PMID- 18341620
TI  - Severe atopic dermatitis is associated with a high burden of environmental
      Staphylococcus aureus.
AB  - BACKGROUND: About 90% of patients with atopic dermatitis (AD) are colonized with
      Staphylococcus aureus. S. aureus worsens AD by secreting superantigens and
      structural molecules within the cell wall that induce skin inflammation.
      Therefore, S. aureus in the home may contribute to persistent skin inflammation
      and disease severity. OBJECTIVE: To quantify S. aureus burden in homes of
      participants with AD of varying severities. METHODS: Participants with mild
      (n=18), moderate (n=14), severe (n=15), and no AD (n=15), collected dust from
      their bed and bedroom floor, and from their home vacuum cleaner bag. DNA was
      extracted from dust samples, and the S. aureus-specific femB gene was quantified
      using quantitative real-time PCR. Data was log-transformed, and then
      statistically analysed with anova, student's t-test, and Spearman's r. RESULTS:
      Participants with severe AD (geometric mean: 14.67 pg/mg dust) had significantly
      more S. aureus DNA in their bed dust than those with moderate (0.41 pg/mg dust,
      P<0.0001), mild (1.42 pg/mg dust, P=0.0051), and no AD [0.09 pg/mg dust, P<0.0001
      (t-test)]. Similar patterns were observed for dust from the bedroom floors and
      vacuum bags. S. aureus DNA was highest in dust from beds as compared with bedroom
      floors or vacuum bags (medians: 1.51, 0.69, 0.21 pg/mg dust, respectively;
      P=0.007). Eczema Area and Severity Index scores correlated with S. aureus DNA
      from the bed (Spearman's r=0.7263; P=0.0004) and floor (0.6846; P=0.0002) dust,
      but not with the vacuum bag dust (0.3783; 0.0684). CONCLUSIONS: In the home and
      especially the bedroom, higher levels of S. aureus may contribute to disease
      severity and persistence in AD patients.

PMID- 18341621
TI  - Aurora kinase B is an independent protective factor in superficial bladder
      tumours with a dysfunctional G1 checkpoint.
AB  - OBJECTIVES: To investigate the clinical role of Aurora kinases (essential for
      regulating mitosis) in human bladder pathogenesis, by quantifying Aurora kinase A
      and B, phospho-Aurora A, and phospho-Rb and p53 in bladder tumours, analysing the
      correlations between expression and clinicopathological features. PATIENTS AND
      METHODS: We evaluated levels of Aurora A, B, phospho-Aurora A, phospho-Rb and p53
      in 73 superficial bladder tumours using tissue microarrays and
      immunohistochemistry, and correlated expression with pathological variables and
      clinical outcome. RESULTS: None of the Aurora proteins, when analysed alone,
      significantly predicted either tumour recurrence or progression. In tumours with
      an aberrant G1 checkpoint, assessed by phospho-Rb and p53 status, expression of
      neither Aurora A nor its phosphorylated form predicted either tumour recurrence
      or progression. Surprisingly, high expression of Aurora B in tumours with an
      aberrant G1 checkpoint significantly protected from tumour recurrence. On
      multivariate analysis, Aurora B was the only significant factor that predicted
      tumour recurrence in the presence of either phospho-Rb or mutated p53. This
      difference was not evident in tumours with an intact G1 checkpoint. CONCLUSIONS:
      High expression of Aurora B in superficial bladder tumours with an aberrant G1
      checkpoint significantly protects patients from tumour recurrence. The potential
      application of nonspecific Aurora kinase inhibitors in non-muscle-invasive
      bladder cancer might be detrimental.

PMID- 18341622
TI  - Protein oxidation as a novel biomarker of bladder decompensation.
AB  - OBJECTIVE: To measure the degree to which partial bladder outlet obstruction
      (PBOO) results in oxidative bladder damage, which subcellular components of the
      bladder are affected and whether these changes correlate with bladder function.
      MATERIALS AND METHODS: In all, 32 rabbits were divided into four groups. Each
      group underwent PBOO for 1, 2, 4, and 8 weeks, respectively. Bladder tissue from
      each group was homogenized and separated into subcellular fractions via
      differential centrifugation. The carbonyl content within the subcellular
      fractions, including the nuclear, mitochondrial, and microsomal pellets, was then
      quantified by dot blot analysis. RESULTS: Total bladder oxidation increased with
      duration of obstruction across all subcellular fractions. The largest increase in
      total oxidation occurred between 4 and 8 weeks. Protein oxidation density in the
      nuclear and microsomal fractions both showed increases at 2 weeks obstruction,
      decreases at 4 weeks, and then large increases at 8 weeks. The increase in
      protein oxidation density between 4 and 8 weeks obstruction was most pronounced
      in the microsomal fraction. CONCLUSIONS: Overall bladder protein oxidation
      increased with the duration of obstruction and increased at a greater rate during
      the transition to decompensation. Furthermore, the subcellular fraction that
      exhibited the most oxidation was the microsomal pellet. The amount of protein
      oxidation correlated with the functional changes in the bladder.

PMID- 18341623
TI  - Clinical and pathological features of screen vs non-screen-detected prostate
      cancers: is there a difference?
AB  - OBJECTIVE: To evaluate the clinical and pathological characteristics of screen vs
      non-screen-detected prostate cancers, to determine if there is a difference in
      the same prostate-specific antigen (PSA) range. PATIENTS AND METHODS: In all, 997
      patients who had had a radical prostatectomy were evaluated; 806 were Tyrolean
      screening volunteers, and 191 were from outside Tyrol, representing the 'referred
      prostate cancer' group. PSA level, age, prostate volume and pathological
      characteristics were assessed, as was the amount of over- and under-diagnosis.
      RESULTS: There were no statistically significant differences in patient age or
      PSA levels in the two groups. Even in the same PSA range there were statistically
      significantly more extraprostatic cancers in the referral group, at 31.7% and
      17.4%, respectively. In the referred and screening groups there was over
      diagnosis in 7.9% and 16.8%, and under-diagnosis in 40.8% and 27.8%,
      respectively. CONCLUSION: This study suggests that screening volunteers have a
      statistically significantly higher rate of organ-confined prostate cancers, and a
      statistically significantly lower rate of extracapsular extension and positive
      surgical margins than their counterparts in the referral group even in the same
      PSA range. As the pathological stage and surgical margin status are significant
      predictors of recurrence, these findings support the concept of PSA screening.

PMID- 18341624
TI  - Conservative management in selected patients with upper tract urothelial
      carcinoma compares favourably with early radical surgery.
AB  - OBJECTIVE: To compare the outcomes of patients treated for upper tract urothelial
      carcinoma with either immediate nephroureterectomy (NU) or initial endoscopic
      management. PATIENTS AND METHODS: The treatments of 108 patients (120 renal
      units) at the authors' institution were retrospectively reviewed and divided into
      two groups, i.e. those who received immediate NU and those who had conservative
      initial therapy, which included renal units solely treated with endoscopy with or
      without delayed NU. Overall and disease-specific survival (DSS) were compared
      between the treatment groups. RESULTS: There were 48 low-grade tumours, of which
      27 (56%) were managed conservatively and 21 (44%) by immediate NU. Seven patients
      treated conservatively had stage or grade progression and had delayed NU. The
      mean (sd) DSS at 5 years in patients with low-grade disease was equally good for
      conservative treatment and immediate NU, at 86.2 (9.1)% vs 87.4 (8.4)% (P =
      0.909). There were 68 high-grade tumours, of which 12 (18%) patients had
      conservative management and 56 (82%) had immediate NU. Among the former, seven of
      12 had a solitary kidney and three had bilateral disease. In patients managed
      endoscopically, four of 30 (13%) required delayed NU. The DSS for the
      conservative and immediate NU groups were 68.6 (18.6)% vs 75.0 (8.1)% (P =
      0.528). CONCLUSION: Management with a conservative approach in selected patients
      provides comparable outcomes to immediate NU in patients with low-grade disease.

PMID- 18341625
TI  - Mitogenic and anti-apoptotic actions of adipocyte-derived hormone leptin in
      prostate cancer cells.
AB  - OBJECTIVE: To investigate the proliferative and anti-apoptotic effects of leptin
      on human prostate cancer cells, and the role of related signalling pathways in
      mediating these actions, as obesity is a possible risk factor for prostate cancer
      and leptin, an adipocyte-derived hormone, has mitogenic action in various cell
      types. MATERIALS AND METHODS: Two human prostate cancer cell lines, DU145 and PC
      3, were treated with leptin (5-100 ng/mL) for up to 48 h. Under serum-free
      conditions, cell proliferation was measured using a colorimetric tetrazolium
      assay and apoptosis by an enzyme-linked immunosorbent assay measuring cell death.
      Also, the phosphorylation of ERK1/2 and Akt was detected by Western blotting, and
      specific inhibitors of mitogen-activated protein kinase (MAPK) (PD98059; 40
      microm) and phosphatidylinositol 3-kinase (PI3-K, LY294002; 40 microm) were used
      to evaluate the role of these signalling pathways. RESULTS: Leptin dose
      dependently increased the cell number in both cell lines for up to 48 h of
      incubation, the mean (sem) percentage of the control being 189 (4.3)% for DU145
      and 173 (7.5)% for PC-3 (100 ng/mL leptin, 48 h; P < 0.01). Leptin also
      significantly reduced the number of apoptotic cells after 24 h of treatment, dose
      dependently caused ERK1/2 and Akt phosphorylation; pretreatment with inhibitors
      of MAPK and PI3-K inhibited these responses. CONCLUSION: These results show that
      chronic increases in leptin might enhance the growth of prostate cancer via the
      MAPK and PI3-K pathways. Further studies are needed to investigate whether the
      ability of leptin to stimulate mitogenic/anti-apoptotic signal transduction
      pathways could represent a target for anticancer drug discovery.

PMID- 18341626
TI  - Progression after radical prostatectomy for men in their thirties compared to
      older men.
AB  - OBJECTIVE: To assess the biochemical outcome after radical prostatectomy (RP)
      specifically for men aged 30-39 years, as previous studies suggest that prostate
      cancer in young men might be more aggressive. PATIENTS AND METHODS: From a large
      (15 899) database of RPs (1975-2007) we identified 42 men aged 30-39, 893 aged 40
      49, 4085 aged 50-59, 3766 aged 60-69, and 182 men aged > or =70 years old. The
      clinical characteristics and treatment outcomes were compared between men aged 30
      39 years and older men. RESULTS: Among the men in their thirties, 81% had organ
      confined disease in the RP specimen, vs 62% of men aged > or =40 years. At a mean
      follow-up of 5 years, there was biochemical progression in 4.8% of men in their
      thirties and 16.1% of men age > or =40 years (P = 0.055). The corresponding 5
      year biochemical progression-free survival estimates were 95% for men in their
      thirties and 83% for men aged > or =40 years (P = 0.045). On multivariate
      analysis, increasing age was a significant independent predictor of biochemical
      progression. CONCLUSION: Contrary to earlier reports, in the present study men in
      their thirties did not have more aggressive disease. Instead, they had more
      favourable pathological features and progression-free survival rates than their
      older counterparts. After controlling for other prognostic variables on
      multivariate analysis, being in the fourth decade was independently associated
      with a lower risk of biochemical progression. These results suggest that early
      aggressive treatment for these patients with a long life-expectancy is associated
      with favourable long-term biochemical outcomes.

PMID- 18341627
TI  - The utility of prostate-specific antigen velocity thresholds in clinical
      practice: a population-based analysis.
AB  - OBJECTIVE: To investigate the ability of prostate-specific antigen velocity
      (PSAV) to predict prostate cancer, and assess the test characteristics of several
      PSAV thresholds for identifying prostate cancer and high-grade cancers. PATIENTS
      AND METHODS: From a population-based database of PSA results, men with an initial
      PSA level of <10.0 ng/mL, taken between I January 1994 and 31 December 2003, were
      identified. Those with three or more PSA tests before diagnosis, taken over > or
      =18 months, were included. Men were followed for a diagnosis of prostate cancer
      or histologically confirmed benign disease until 31 December 2003. RESULTS: In
      all, 24 709 men were included, with 716 (2.9%) diagnosed with prostate cancer and
      1488 (6.0%) with benign histology. The mean (10.38 vs 0.43 ng/mL/year) and median
      (1.47 vs 0.03 ng/mL/year) PSAV were considerably higher in men with prostate
      cancer than in those with no cancer (P < 0.001). There was no PSAV threshold that
      could reliably identify prostate cancer or high-grade cancers without requiring
      many men to proceed to prostate biopsy. CONCLUSION: In this population, PSAV had
      additional value over one PSA value in identifying men with prostate cancer. Many
      men with prostate cancer might have a 'normal' (<0.75 ng/mL/year) PSAV. As with
      total PSA level, there was no PSAV threshold that could reliably predict prostate
      cancer, but rather a continuum of risk of cancer associated with PSAV level.

PMID- 18341628
TI  - Endoscopic incision for obstruction of vesico-ureteric anastomosis in
      transplanted kidneys.
AB  - OBJECTIVE: To report our experience of endoscopic incision for obstruction of
      vesico-ureteric anastomosis (VUA) in transplanted kidneys. PATIENTS AND METHODS:
      Between February 2001 and March 2006, six men and two women (mean age 38 years,
      range 27-57) with VUA obstruction in their transplanted kidneys were treated by
      percutaneous nephrostomy and endoscopic incision. After the anastomosis was
      completely cut, two JJ stents were placed in the ureter for 4-6 weeks. During the
      follow-up, serum urea, creatinine and uric acid levels were measured, and urine
      culture, ultrasound examination and washout renal scintigraphy were performed
      every month for the first 6 months, then every 3 months. RESULTS: In all, 12
      procedures of endoureterotomy were performed and all procedures resulted in
      successful incision of the obstruction. There were no complications during or
      after the procedures. The retrograde and antegrade endoureterotomies were
      performed with four procedures in two patients and eight procedures in six
      patients, respectively. At a mean (range) follow-up of 16 (4-45) months, five of
      the eight patients had ureteric patency and stable renal function. In three
      patients there was a recurrence of obstructive uropathy, immediately after JJ
      stent removal, which finally required open surgical correction. CONCLUSIONS:
      Percutaneous nephrostomy and endoscopic incision is safe and effective for
      obstruction of VUA in transplanted kidney, and it can be the initial therapy for
      ureteric obstruction in transplanted kidneys; however, open surgical
      reconstruction should be considered if the initial endoscopic incision procedure
      fails.

PMID- 18341629
TI  - Advances in clinical research in sickle cell disease.
AB  - Sickle cell disease continues to cause significant morbidity and mortality
      despite increases in life expectancy. This review looks at recent translational
      research in sickle cell disease, covering the red cell membrane, the vascular
      endothelium, local and systemic inflammation and the potentially pivotal role of
      nitric oxide as a key regulator of sickle cell complications. Clinical research
      reviewed includes pulmonary hypertension, which is emerging as a particularly
      deadly scourge of adults with any haemolytic anaemia, and newer insights into
      older, more established complications and treatments, such as red cell
      transfusions, the need for and use of iron chelation and avascular necrosis.
      Finally, recent studies about those factors that affect the day-to-day lives of
      persons with sickle cell disease, pain and neuropsychiatric functioning, are
      discussed.

PMID- 18341630
TI  - Disorders of red cell membrane.
AB  - Studies during the last three decades have enabled the development of detailed
      molecular insights into the structural basis of altered function in various
      inherited red cell membrane disorders. This review highlights our current
      understanding of molecular and mechanistic insights into various inherited red
      cell membrane disorders involving either altered membrane structural organization
      (hereditary spherocytosis, hereditary elliptocytosis and hereditary ovalocytosis)
      or altered membrane transport function (hereditary stomatocytosis). The molecular
      basis for the vast majority of cases of hereditary spherocytosis, elliptocytosis
      and ovalocytosis have been fully defined while little progress has been made in
      defining the molecular basis for hereditary stomatocytosis. Mutations in a number
      of distinct genes account for hereditary spherocytosis and elliptocytosis, while
      a single genetic defect accounts for all cases of hereditary ovalocytosis. Based
      on these molecular insights, a comprehensive understanding of the structural
      basis for altered membrane function has been developed. Loss of vertical linkage
      between membrane skeleton and lipid bilayer leads to membrane loss in hereditary
      spherocytosis, while weakening of lateral linkages between skeletal proteins
      leads to membrane fragmentation and surface area loss in hereditary
      elliptocytosis. Importantly, the severity of anaemia in both these disorders is
      directly related to extent of membrane surface area loss. Splenectomy results in
      amelioration of anaemia.

PMID- 18341631
TI  - Fibrinolytic inhibitor levels and polymorphisms in Behcet disease and their
      association with thrombosis.
AB  - This study aimed to assess the fibrinolytic inhibitors and their association with
      thrombosis in Behcet disease. Thrombin activatable fibrinolysis inhibitor (TAFI)
      (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) levels (P = 0.022) were
      significantly higher in 79 patients than in 84 controls. No significant
      differences were observed in CPB2 (TAFI) Thr325Ile and SERPINE1 (PAI1) 4G/5G
      polymorphism distribution between patients and controls. TAFI activity levels
      were significantly higher in patients with thrombosis than in those without
      thrombosis (P = 0.024). In conclusion, the increased TAFI levels in Behcet
      disease could contribute to the increased risk of thrombosis observed in these
      patients.

PMID- 18341632
TI  - The VWF/ADAMTS13 axis in the antiphospholipid syndrome: ADAMTS13 antibodies and
      ADAMTS13 dysfunction.
AB  - Autoantibodies to ADAMTS13 (a disintegrin-like and metalloprotease with
      thrombospondin type I motif, member 13) play an important role in the development
      of microthrombosis in thrombotic thrombocytopenic purpura (TTP). In severe cases
      of antiphospholipid syndrome (APS), microthrombosis can occur similar to that
      seen in TTP, suggesting possible mutual pathogenic factors. However, the role of
      ADAMTS13 in APS is unknown. We hypothesised that aberrations in ADAMTS13 may
      occur in APS and evaluated ADAMTS13 and von Willebrand factor (VWF) in 68
      patients with antiphospholipid antibodies (aPA) including 52 with APS. Thirty
      three (49%) had IgG anti-ADAMTS13 with 12 of these patients having reduced
      ADAMTS13 activity, suggesting neutralising antibodies. Low ADAMTS13 activity
      (median 34%) was demonstrated in 22/68 (33%), all with normal ADAMTS13 antigen
      levels consistent with dysfunctional ADAMTS13. Reduced ADAMTS13 activity was not
      secondary to elevated von Willebrand factor (VWF), or increased VWF secretion
      (normal VWF propeptide), although a reduced VWF clearance was noted in APS.
      Analysis found no associations between the ADAMTS13 abnormalities and any aPA
      profile or thrombotic/obstetric complications, although this study was not
      adequately powered to address clinical associations. Nevertheless, these findings
      highlight that ADAMTS13 autoantibodies and ADAMTS13 dysfunction can occur in APS,
      and although the clinical significance remains undetermined, ADAMTS13 dysfunction
      may be contributory to thrombogenesis in autoimmune conditions other than TTP.

PMID- 18341633
TI  - Redox homeostasis modulates the sensitivity of myeloma cells to bortezomib.
AB  - The use of proteasome inhibitors have been a major advance in the treatment of
      multiple myeloma (MM), but their mechanisms of action remain largely unclear. A
      better understanding of the cellular events downstream of proteasome inhibition
      is essential to improve the response and identify new combination therapies for
      MM and other malignancies. This study analysed the relationships between redox
      homeostasis and bortezomib treatment in MM cells. Our data showed that decreasing
      intracellular glutathione through buthionine sulfoximine treatment strongly
      enhances bortezomib toxicity, whilst antioxidants protect MM cells from
      bortezomib-mediated cell death. Bortezomib treatment decreases intracellular
      glutathione both in MM cell lines and in malignant plasma cells obtained from MM
      patients. Glutamate-cysteine ligase (GCLM) and haem-oxygenase-1 (HMOX1), two
      genes involved in the Nrf-2-mediated antioxidant response, as well as two
      eIF2alpha-downstream transcription factors, activating transcription factor 4
      (ATF4) and C/EBP homologous protein (CHOP), are upregulated, indicating that
      redox-related adaptive responses are initiated in bortezomib-treated MM cells.
      These findings demonstrate tight links between sensitivity to proteasome
      inhibition and redox homeostasis in MM cells and have potential implications for
      treatment.

PMID- 18341634
TI  - The insulin-like growth factor-I receptor inhibitor NVP-AEW541 provokes cell
      cycle arrest and apoptosis in multiple myeloma cells.
AB  - Multiple myeloma (MM) is a B-cell malignancy characterized by accumulation of
      monoclonal plasma cells in the bone marrow (BM). Despite recent advances in the
      treatment, MM represents an incurable disease for which development of new
      therapies is required. We report the antimyeloma effect of NVP-AEW541, a small
      molecule that belongs to the pyrrolo[2,3-d]pyrimidine class, identified as a
      selective inhibitor of the insulin-like growth factor-I receptor (IGF-IR) in
      vitro kinase activity. NVP-AEW541 had a potent cytotoxic effect on fresh cells
      and in a murine MM model. NVP-AEW541 partially abrogated the proliferative
      advantage conferred by the coculture with BM stromal cells and the presence of
      growth factors produced by the BM microenvironment. In addition, NVP-AEW541
      potentiated the action of drugs, such as bortezomib, lenalidomide, dexamethasone
      or melphalan. Moreover the triple combination of NVP-AEW541, dexamethasone and
      bortezomib resulted in a significant increase in growth inhibition. Mechanistic
      studies indicated that NVP-AEW541 provoked a marked cell cycle blockade
      accompanied by pRb downregulation. Interestingly, NVP-AEW541 increased the levels
      of p27 associated with a reduction in the CDK2 activity. Finally, NVP-AEW541
      induced cell death through caspase-dependent and -independent mechanisms. All
      these data, suggest the potential effect of IGF-IR kinase inhibitors as
      therapeutic agents for MM patients.

PMID- 18341635
TI  - beta-Dystroglycan modulates the interplay between actin and microtubules in human
      adhered platelets.
AB  - To maintain the continuity of an injured blood vessel, platelets change shape,
      secrete granule contents, adhere, aggregate, and retract in a haemostatic plug.
      Ordered arrays of microtubules, microfilaments, and associated proteins are
      responsible for these platelet responses. In full-spread platelets, microfilament
      bundles in association with other cytoskeleton proteins are anchored in focal
      contacts. Recent studies in migrating cells suggest that co-ordination and direct
      physical interaction of microtubules and actin network modulate adhesion
      development. In platelets, we have proposed a feasible association between these
      two cytoskeletal systems, as well as the participation of the dystrophin
      associated protein complex, as part of the focal adhesion complex. The present
      study analysed the participation of microtubules and actin during the platelet
      adhesion process. Confocal microscopy, fluorescence resonance transfer energy and
      immunoprecipitation assays were used to provide evidence of a cross-talk between
      these two cytoskeletal systems. Interestingly, beta-dystroglycan was found to act
      as an interplay protein between actin and microtubules and an additional
      communication between these two cytoskeleton networks was maintained through
      proteins of focal adhesion complex. Altogether our data are indicative of a
      dynamic co-participation of actin filaments and microtubules in modulating focal
      contacts to achieve platelet function.

PMID- 18341636
TI  - Mutated and non-mutated TP53 as targets in the treatment of leukaemia.
AB  - TP53 is mutated in 10-20% of cases of chronic lymphocytic leukaemia (CLL) and 3
      8% of cases of acute myeloid leukaemia (AML). Recently, two classes of compounds
      that restore the function of p53 in tumours have been described. PRIMA-1 (p53
      dependent reactivation and induction of massive apoptosis) restores the wild-type
      conformation of mutant TP53, whereas RITA (reactivation of p53 and induction of
      tumour cell apoptosis) increases intracellular levels of p53. We evaluated the
      effects of RITA alone and in combination with PRIMA-1 or conventional cytostatics
      on leukaemic cells isolated from AML and CLL patients. AML samples with -17,
      which are more resistant to daunorubicin and cytarabine compared with samples
      without -17, were effectively killed by PRIMA-1. RITA, which stabilizes the
      function of wild-type p53, induced apoptosis in AML cells. In contrast to that
      seen with PRIMA-1, AML patient samples without -17 were significantly more
      sensitive to RITA. Similarly, RITA exerted dose-dependent apoptosis and
      cytotoxicity in CLL cells, which was significantly more pronounced in samples
      without hemizygous TP53 deletion. Notably, a synergistic effect was observed in
      all CLL samples with RITA and fludarabine in combination. In both AML and CLL
      cells exposure to RITA resulted in induction of intracellular p53. We conclude
      that small molecules targeting p53 might be of clinical importance in the future
      for treating drug-resistant leukaemia.

PMID- 18341637
TI  - Cytogenetic abnormalities and clinical correlations in peripheral T-cell
      lymphoma.
AB  - Cytogenetic correlations among most types of peripheral T-cell lymphoma (PTCL)
      have not been very informative to date. This study aimed to identify recurrent
      chromosomal abnormalities in angioimmunoblastic T-cell lymphoma (AITL), ALK
      negative anaplastic large cell lymphoma (ALK-ALCL) and peripheral T-cell
      lymphoma, unspecified (PTCL-US), and to evaluate their prognostic value. We
      reviewed the cytogenetic findings of 90 previously-diagnosed cases of PTCL and
      correlated the cytogenetic findings with the specific histological subtype. The
      most common abnormalities for AITL were 5q (55%), 21 (41%) and 3q (36%) gains,
      concurrent trisomies of 5 and 21 (41%), and loss of 6q (23%). In ALK(-) ALCL,
      gains of 1q (50%) and 3p (30%), and losses of 16pter (50%), 6q13q21 (30%), 15
      (30%), 16qter (30%) and 17p13 (30%) were frequent findings. In PTCL-US, frequent
      gains involved 7q22q31 (33%), 1q (24%), 3p (20%), 5p (20%), and 8q24qter (22%),
      and losses of 6q22q24 (26%) and 10p13pter (26%). We did not observe any
      association between specific chromosomal abnormalities and overall survival (OS).
      However, cases with complex karyotypes, most frequently observed in ALK(-) ALCL
      and PTCL-US, had a significantly shorter OS. Although, genetic differences were
      noted in these subtypes, further studies are needed to determine the key
      pathogenetic events in PTCL.

PMID- 18341638
TI  - The effect of anti-CD40 ligand in immune thrombocytopenic purpura.
AB  - Immune thrombocytopenic purpura (ITP) is mediated by antiplatelet autoantibodies
      possibly involving CD40:CD40L co-stimulation. Two humanized anti-CD40L monoclonal
      antibodies, hu5c8 and IDEC-131, were evaluated in 46 patients with chronic
      refractory ITP. Fifteen patients were treated with 20 mg/kg of hu5c8: four (27%)
      had complete responses (CR) and two (13%) had partial responses (PR). Three
      responders to hu5c8 were successfully retreated with IDEC-131, demonstrating its
      efficacy. Thirty-one subsequent patients were treated with 5-20 mg/kg per
      infusion of IDEC-131: five (16%) responded (one CR and four PR). The 24% (11/46)
      overall response rate demonstrates the potential role of CD40-CD40L in the
      pathogenesis of ITP.

PMID- 18341639
TI  - Acute myeloid leukaemia blast cells with a tyrosine kinase domain mutation of
      FLT3 are less sensitive to lestaurtinib than those with a FLT3 internal tandem
      duplication.
AB  - FLT3 tyrosine kinase domain mutations (FLT3/TKDs) are associated with a
      favourable prognosis in acute myeloid leukaemia (AML), unlike FLT3 internal
      tandem duplications (FLT3/ITDs) that have a poor prognosis. Whilst FLT3/ITD+
      cells are more susceptible to the cytotoxic effects of FLT3 inhibitors than wild
      type (WT) cells, the sensitivity of FLT3/TKD+ cells to therapeutic agents is
      unclear, as is the importance of the mutant level. We therefore studied the
      effect of cytarabine and the FLT3 inhibitor lestaurtinib, either alone or in
      combination, on in vitro survival of blast cells from 36 cases of AML (14
      FLT3/WT, 11 FLT3/ITD+ and 11 FLT3/TKD+). All three groups showed similar
      sensitivity to the cytotoxic effects of cytarabine but FLT3/ITD mutant level was
      inversely correlated with cytarabine cytotoxicity (P = 0.04) whereas FLT3/TKD
      mutant level had no impact. FLT3/TKD+ cells showed a similar response to
      lestaurtinib as FLT3/WT cells, whereas FLT3/ITD+ cells were more sensitive (P =
      0.004). There was no correlation between mutant level and lestaurtinib
      sensitivity for either FLT3/ITD+ or FLT3/TKD+ cells. Synergistic cytotoxicity of
      lestaurtinib plus cytarabine was demonstrated in all three groups. These results
      suggest that FLT3/TKD+ and FLT3/WT cases should not be differentiated when
      considering patients for treatment with FLT3 inhibitors.

PMID- 18341640
TI  - Is the beta thalassaemia trait of clinical importance?
AB  - Although the beta thalassaemia trait affects millions of people worldwide, there
      have been no controlled studies to determine whether it is associated with any
      clinical disability or abnormal physical signs. To address this question, 402
      individuals were studied: 217 with beta thalassaemia trait, of whom 154 were
      aware of the diagnosis and 63 were unaware until after the completion of the
      study; 89 normal controls; and 96 controls with mild hypochromic anaemia. There
      was a significant increase in symptoms ascribable to anaemia and episodes of
      pyrexia in those with the beta thalassaemia trait that were not influenced by
      prior knowledge that they had this condition. There was no difference in physical
      findings, notably splenomegaly, between those with beta thalassaemia trait and
      either control group.

PMID- 18341641
TI  - Bortezomib (PS-341) in patients with human herpesvirus 8-associated primary
      effusion lymphoma.

PMID- 18341642
TI  - A robust linkage analysis method using combined allele sharing and transmission
      disequilibrium information from case-parent tetrad families.
AB  - There are two types of linkage information, the allele sharing information and
      transmission disequilibrium information, that can be extracted from case-parent
      tetrad families for deriving statistics for test of linkage. By extracting allele
      sharing information the mean test can be derived. By extracting transmission
      disequilibrium information the transmission/disequilibrium test (TDT) can be
      derived. The power performances of the two tests are different with respect to
      the extent of linkage disequilibrium. The TDT is more powerful than the mean test
      when the extent of linkage disequilibrium is moderate to strong, but the mean
      test has better power performance than the TDT when linkage disequilibrium is
      weak. Some previous studies have proposed several post-combination analysis
      methods, which combine the two tests after they are derived using the two types
      of linkage information respectively, to yield robust test statistics against the
      interference of linkage disequilibrium. Instead of adopting the post-combination
      approach, in this paper we investigate the approach of using the pre-combination
      idea to yield robust statistics for test of linkage. The pre-combination methods
      combine the two types of linkage information first, and then use the combined
      information to construct robust test statistics. Simulation studies are conducted
      to compare the power performances of the proposed pre-combination tests with
      those of the existing post-combination methods.

PMID- 18341643
TI  - Ethanol induces apoptotic death of beta-endorphin neurons in the rat hypothalamus
      by a TGF-beta 1-dependent mechanism.
AB  - BACKGROUND: We have previously shown that developing beta-endorphin neurons, in
      the arcuate nucleus of the hypothalamus become increasingly apoptotic when
      exposed to ethanol. As in the previous study we have observed an involvement in
      transforming growth factor beta 1 (TGF-beta1) in mediation of the apoptotic
      process, the present study was conducted to determine the ethanol-induced changes
      in this apoptotic regulatory peptide signaling in the arcuate nucleus of the
      hypothalamus of neonatal rats. METHODS: Pups were exposed to 11.34% ethanol in a
      milk-based diet or control diet on postnatal day (PND) 3 to PND7. Two hours after
      the last daily feeding, brains were collected and frozen in liquid nitrogen for
      analysis of various apoptosis regulatory proteins in the arcuate tissue by
      Western blots. Some animals were fixed in 4% paraformaldehyde and analyzed
      immunohistochemically. RESULTS: Ethanol exposure increased apoptotic death of
      beta-endorphin neurons in the arcuate nucleus of the hypothalamus. The cell death
      was associated with an increase in the tissue levels of TGF-beta1 in the
      mediobasal hypothalamus. This was correlated with a reduction in the arcuate
      level of retinoblastoma protein (Rb) phosphorylation. The reduced level of Rb
      phosphorylation was associated with an increased protein level of the cyclin
      dependent kinase inhibitor p27/kip but with a decreased protein level of cyclin
      dependent kinase 4 and cyclin D3. In addition, the apoptotic cell death was
      positively correlated with the level of Bclxs but negatively correlated with the
      level of the Bcl2. CONCLUSIONS: These results suggest that ethanol exposure
      increases TGF-beta1 signaling involving Bcl2 and Rb repression that may lead to
      apoptotic death of cells including beta-endorphin neurons in the arcuate nucleus
      of the hypothalamus.

PMID- 18341644
TI  - Na,K-ATPase expression is increased in the lungs of alcohol-fed rats.
AB  - BACKGROUND: Alcohol abuse independently increases the risk of developing the
      acute respiratory distress syndrome (ARDS), a disease characterized by diffuse
      alveolar epithelial damage, lung edema, and consequent severe hypoxemia. Chronic
      alcohol abuse increases alveolar epithelial permeability both in vitro and in
      vivo, in part due to altered tight junction formation. However, both alcohol-fed
      animals and otherwise healthy alcoholic humans do not have pulmonary edema at
      baseline, even though their lungs are highly susceptible to acute edematous
      injury in response to inflammatory stresses. This suggests that active fluid
      transport by the alveolar epithelium is preserved or even augmented in the
      alcoholic lung. Chronic alcohol ingestion increases expression of apical sodium
      channels in the alveolar epithelium; however, its effects on the Na,K-ATPase
      complex that drives sodium and fluid transport out of the alveolar space have not
      been examined. METHODS: Age- and gender-matched Sprague-Dawley rats were fed the
      Lieber-DeCarli liquid diet containing either alcohol or an isocaloric
      substitution (control diet) for 6 weeks. Gene and protein expression of lung Na,K
      ATPase alpha1, alpha2, and beta1 subunits were quantified via real-time PCR and
      immunobiological analyses, respectively. Alcohol-induced, Na,K-ATPase-dependent
      epithelial barrier dysfunction was determined by calculating lung tissue wet:dry
      ratios following an ex vivo buffer-perfused challenge for 2 hours in the presence
      of ouabain (10(-4) M), a Na,K-ATPase inhibitor. RESULTS: Chronic alcohol
      ingestion significantly increased gene and protein expression of each Na,K-ATPase
      subunit in rat lungs. Immunohistochemical analyses of the alcoholic lung also
      revealed that protein expression of the Na,K-ATPase alpha1 subunit was increased
      throughout the alveolar epithelium. Additionally, lungs isolated from alcohol-fed
      rats developed more edema than comparably treated lungs from control-fed rats, as
      reflected by increased lung tissue wet:dry ratios. CONCLUSIONS: These findings
      indicate that chronic alcohol ingestion, which is known to increase alveolar
      epithelial paracellular permeability, actually increases the expression of Na,K
      ATPase in the lung as a compensatory mechanism. This provides a potential
      explanation as to why the otherwise healthy alcoholic does not have evidence of
      pulmonary edema at baseline.

PMID- 18341645
TI  - Ethanol selectively attenuates NMDAR-mediated synaptic transmission in the
      prefrontal cortex.
AB  - BACKGROUND: Brain imaging studies have revealed abnormal function in the
      prefrontal cortex (PFC) of alcoholics that may contribute to the impulsive
      behavior and lack of control over drinking that characterizes this disorder.
      Understanding how ethanol affects the physiology of PFC neurons may help explain
      this loss of control and lead to better treatments for alcohol addiction. In a
      previous study from this laboratory, we showed that ethanol inhibits complex
      patterns of persistent activity (known as "up-states") in medial PFC (mPFC)
      neurons in a reversible and concentration-dependent manner. METHODS: In the
      current study, whole-cell patch clamp recordings were used to directly examine
      the effects of ethanol on the glutamatergic and GABAergic components that
      underlie persistent activity. RESULTS: In deep-layer mPFC pyramidal neurons,
      ethanol reversibly attenuated electrically evoked N-methyl-D-aspartate-type
      glutamate receptor (NMDAR)-mediated EPSCs. Significant inhibition was observed at
      concentrations as low as 22 mM, equivalent to a blood ethanol concentration
      (0.1%) typically associated with legal limits for intoxication. In contrast to
      NMDA responses, neither evoked nor spontaneous EPSCs mediated by alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid-type glutamate receptor were affected
      by ethanol at concentrations as high as 88 mM, a concentration that can be fatal
      to non-tolerant individuals. At similar concentrations, ethanol also had little
      effect on spontaneous or evoked IPSCs mediated by a-type gamma-aminobutyric acid
      receptor. Finally, mPFC neurons showed little evidence of GABAR-mediated tonic
      current and this was unaffected by ethanol. CONCLUSIONS: Together, these results
      suggest that NMDAR-mediated processes in the mPFC may be particularly susceptible
      to disruption following the acute ingestion of ethanol.

PMID- 18341646
TI  - Adipose differentiation-related protein is a reliable lipid droplet marker in
      alcoholic fatty liver of rats.
AB  - BACKGROUND: Adipose differentiation-related protein (ADRP) is a lipid droplet
      associated protein that coats cytoplasmic lipid droplets. The present study
      evaluated whether alcohol feeding enhances ADRP expression and whether ADRP is a
      lipid droplet marker in alcoholic fatty liver of rats. Because medium-chain
      triglycerides (MCT) reduce alcoholic hepatosteatosis, their effects on ADRP were
      also evaluated. METHODS: Fatty liver was induced in rats by the consumption of
      the Lieber-DeCarli alcohol liquid diet with or without replacement of long-chain
      triglycerides (LCT) by MCT (32% of calories). Immunohistochemical staining for
      ADRP was performed in formalin-fixed, paraffin-embedded liver sections. ADRP
      immunostaining was quantified by image analysis. Triacylglycerol was measured
      chemically. ADRP mRNA and protein were analyzed by real-time polymerase chain
      reaction and western blot, respectively. Double staining technique was performed
      to distinguish ADRP from glycogen in hepatocytes. RESULTS: Alcohol feeding for 21
      days increased ADRP staining in the centrilobular and mid zonal regions of the
      liver lobules coincident with fat deposition in the liver. Replacing LCT in the
      alcohol diet with MCT diminished ADRP immunostaining in parallel with reduced
      steatosis. MCT also attenuated the up-regulation of ADRP mRNA and protein after
      alcohol. In steatotic hepatocytes ADRP selectively stained the surface of
      macrovesicular and microvesicular lipid droplets. ADRP immunostaining
      quantitatively correlated with hepatic triacylglycerol levels, validating ADRP as
      a reliable lipid droplet marker. Compared with hematoxylin and eosin stains, ADRP
      was more sensitive in detecting microvesicular lipid droplets. ADRP
      immunostaining also distinguished lipid droplets from glycogen, as demonstrated
      by double staining for ADRP and glycogen. CONCLUSIONS: Alcohol induction of fatty
      liver enhances ADRP expression and MCT oppose the alcohol effects. ADRP is a
      reliable and sensitive marker for lipid droplets in alcoholic fatty liver. ADRP
      immunostaining permits quantification of fatty change in hepatocytes and can be
      used as an ancillary technique in assessing the efficacy of diets or drugs
      against hepatosteatosis.

PMID- 18341647
TI  - A voluntary oral ethanol-feeding rat model associated with necroinflammatory
      liver injury.
AB  - BACKGROUND: The intragastric (IG) ethanol infusion model results in fatty liver,
      necrosis, inflammation and fibrosis. This model was utilized to study the
      pathogenesis of alcoholic liver disease (ALD). Disadvantages of the IG model
      include maintenance of the animals and equipment expense. To develop a voluntary
      feeding model for ALD, we took advantage of two important observations in the IG
      model: (i) female rats demonstrate greater severity of alcohol-induced liver
      injury than males and (ii) rats fed fish oil as a source of fatty acids develop
      more severe alcoholic liver injury than rats fed other fatty acids with ethanol.
      METHODS: Female Wistar rats (205 to 220 g) were fed for 8 weeks a diet containing
      8% ethanol, fish oil (30% of calories), protein, and dextrose. Pair-fed controls
      (FD) received dextrose in amounts isocaloric to ethanol. The following
      measurements were made: liver pathology [fatty liver (0 to 4), necrosis,
      inflammation and fibrosis by Sirius Red], endotoxin and alanine aminotransferase
      (ALT) in plasma, urine ethanol, lipid peroxidation, nuclear factor kappa-B (NF
      kappaB) and mRNA levels for tumor necrosis factor-alpha (TNF-alpha),
      cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Protein
      levels for iNOS and nitrotyrosine were evaluated by immunohistochemistry and
      Western Blot analysis. Liver proteasome and cytochrome P450 2E1 activity and
      protein levels of asialoglycoprotein receptor (ASGPR) were also evaluated. In
      addition, mRNA levels of fibrogenic markers were assessed. RESULTS: All animals
      lost weight for the initial 2 to 3 weeks but then gained weight until killing at
      8 weeks. There was, however, a significant difference (p < 0.05) in weight
      between the ethanol-fed (Etoh) and (FD) groups at the end of the experiment. The
      mean urine ethanol levels ranged between 190 and 240 mg/dl. The severity of
      pathological changes was greater (p < 0.01) in Etoh vs. FD: fatty liver, 3.0 +/-
      1.2 vs. 1.2 +/- 0.4; necrosis (foci/mm(2)), 3.9 +/- 2.3 vs. 0.4 +/- 0.3;
      inflammation (cells/mm(2)), 19.0 +/- 6.3 vs. 1.8 +/- 0.6. Centrilobular collagen
      deposition (% area), assessed by Sirius Red staining, was greater in Etoh vs. FD.
      Levels of endotoxin, ALT, CYP2E1 and lipid peroxidation markers were also higher
      (p < 0.01) in Etoh vs. FD. Levels of NF-kappaB and mRNA of pro-inflammatory
      mediators (TNF-alpha, COX-2, iNOS) and procollagen-I were increased (p < 0.05) in
      ethanol-fed rats. Immunohistochemical analysis showed more intense staining for
      both iNOS and nitrotyrosine in the centrilobular areas in the Etoh vs. FD groups.
      The greater area of positive staining for iNOS and nitrotyrosine in Etoh vs. FD
      was confirmed by Western Blot analysis. An increase in the expression of mRNA for
      profibrogenic genes (p < 0.05) was seen in ethanol-fed rats. CONCLUSIONS: A
      voluntary feeding regimen consisting of fish oil and ethanol in female rats is
      technically less demanding yet produces pathological and biochemical changes
      similar to those observed with the IG model. Pathological changes include fatty
      liver, necrosis and inflammation. Increased NF-kappaB and mRNA and protein levels
      of the pro-inflammatory mediators TNF-alpha, COX-2 and iNOS, coincided with the
      presence of necroinflammatory changes. The voluntary feeding regimen is proposed
      as an alternative to the IG model in the study of alcoholic liver injury.

PMID- 18341648
TI  - Patterns of alcohol consumption and alcohol-impaired driving in the United
      States.
AB  - BACKGROUND: Alcohol-related motor vehicle crashes kill approximately 17,000
      Americans annually and were associated with more than $51 billion in total costs
      in 2000. Relatively little is known about the drinking patterns of alcohol
      impaired (AI) drivers in the United States. METHODS: 2006 Behavioral Risk Factor
      Surveillance System (BRFSS) was analyzed for alcohol consumption and self
      reported AI driving among U.S. adults aged > or =18 years for all states. Alcohol
      consumption was divided into 4 categories: binge/heavy, binge/nonheavy,
      nonbinge/heavy, and nonbinge/nonheavy. Binge drinking was defined as > or =5
      drinks for men or > or =4 drinks for women on one or more occasions in the past
      month, and heavy drinking was defined as average daily consumption of >2
      drinks/day (men) or >1 drink/day (women). The prevalence of AI driving was
      examined by drinking pattern and by demographic characteristics. Logistic
      regression analysis was used to assess the association between drinking patterns
      and AI driving. RESULTS: Five percent of drinkers were engaged in AI driving
      during the past 30 days. Overall, 84% of AI drivers were binge drinkers and 88%
      of AI driving episodes involved binge drinkers. By drinking category,
      binge/nonheavy drinkers accounted for the largest percentage of AI drivers
      (49.4%), while binge/heavy drinkers accounted for the most episodes of AI driving
      (51.3%). The adjusted odds of AI driving were 20.1 (95% CI: 16.7, 24.3) for
      binge/heavy, 8.2 (6.9, 9.7) for binge/nonheavy, and 3.9 (2.4, 6.3) for
      nonbinge/heavy drinkers, respectively. CONCLUSIONS: There is a strong association
      between binge drinking and AI driving. Most AI drivers and almost half of all AI
      driving episodes involve persons who are not heavy drinkers (based on average
      daily consumption). Implementing effective interventions to prevent binge
      drinking could substantially reduce AI driving.

PMID- 18341649
TI  - Strain differences in alcohol-induced neurochemical plasticity: a role for
      accumbens glutamate in alcohol intake.
AB  - BACKGROUND: Repeated alcohol administration alters nucleus accumbens (NAC) basal
      glutamate content and sensitizes the capacity of alcohol to increase NAC
      extracellular glutamate levels. However, the relevance of alcohol-induced changes
      in NAC glutamate for alcohol drinking behavior is under-investigated. METHODS: To
      examine the relationship between genetic variance in alcohol consumption and
      alcohol-induced neuroadaptations within the NAC, in vivo microdialysis was
      conducted in the alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA2/J
      (D2) mouse strains on injections 1 and 8 of repeated alcohol treatment (8 x 2
      g/kg, IP). To confirm an active role for NAC glutamate in regulating alcohol
      drinking behavior, the glutamate reuptake inhibitor dl-threo-beta
      benzyloxyaspartic acid (TBOA) (300 microM) and the Group 2 metabotropic glutamate
      autoreceptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC) (50
      microM) were infused into the NAC of B6 and D2 mice prior to alcohol consumption
      in a 4 bottle-choice test. RESULTS: While strain differences were not apparent
      for NAC basal levels of dopamine, serotonin or gamma-amino butyric acid (GABA),
      repeated alcohol treatment elevated NAC basal glutamate content only in B6 mice.
      Strain differences in both the acute and the sensitized neurochemical responses
      to 2 g/kg alcohol were observed for all neurotransmitters examined. While the
      alcohol-induced rise in NAC dopamine and glutamate levels sensitized in B6 mice,
      a sensitization was not observed in D2 animals. Moreover, B6 mice exhibited a
      sensitized serotonin and GABA response to alcohol followed repeated treatment,
      whereas neither tolerance nor sensitization was observed in D2 animals. An intra
      NAC APDC infusion reduced alcohol intake in both B6 and D2 mice by approximately
      50%. In contrast, TBOA infusion elevated alcohol intake selectively in B6 mice.
      CONCLUSIONS: These data indicate an active role for NAC glutamate in regulating
      alcohol consumption in mice and support the hypothesis that predisposition to
      high alcohol intake involves genetic factors that facilitate alcohol-induced
      adaptations in glutamate release within the NAC.

PMID- 18341650
TI  - Adult transition from at-risk drinking to alcohol dependence: the relationship of
      family history and drinking motives.
AB  - BACKGROUND: Prospective studies have not previously examined whether a family
      history of alcoholism and drinking motives conjointly predict a diagnosed DSM-IV
      alcohol abuse or dependence in adults, despite a large literature that each is
      associated with alcohol consumption. The focus of this study is the conjoint,
      prospective examination of these risk factors in a 10-year longitudinal study of
      adults who were at-risk drinkers at baseline. METHODS: Prospective, population
      based cohort of drinkers aged 18 or older from a Northeastern U.S. area initially
      evaluated for history of alcohol use disorders and drinking motives in 1991 to
      1992. New onset dependence was studied in those who never met the criteria for
      alcohol dependence at baseline (n = 423), and new onset abuse was studied in
      those who never met the criteria for alcohol abuse at baseline (n = 301) and who
      did not develop dependence during the follow-up. RESULTS: Family history
      significantly interacted with 2 baseline drinking motives in predicting new
      onsets of DSM-IV alcohol dependence: drinking to reduce negative affect (OR 3.38;
      95% CI 1.05, 10.9) and drinking for social facilitation (OR 3.88; CI 1.21, 12.5).
      Effects were stronger after conditioning the drinking motives on having a
      positive family history of alcoholism. In contrast, in predicting new onsets of
      alcohol abuse, drinking motives did not have direct effects or interact with
      family history. CONCLUSIONS: Those who drank to reduce negative affect or for
      social facilitation at baseline were at greater risk of alcohol dependence 10
      years later if they also had a family history of alcoholism. These results
      suggest an at-risk group that can be identified prior to the development of
      alcohol dependence. Further, the findings suggest utility in investigating the
      interaction of drinking motives with measured genetic polymorphisms in predicting
      alcohol dependence.

PMID- 18341651
TI  - A haplotype of the DRD1 gene is associated with alcohol dependence.
AB  - BACKGROUND: The D1 dopamine receptor has been involved in a number of brain
      functions, including motor control, inattentive symptoms and reward and
      reinforcement mechanisms. Indeed, DRD1 antagonists may reduce cocaine-seeking
      behavior and the acquisition of cocaine-cue associations. The D1.1/r4532 marker
      of the DRD1 gene has been associated with a large set of phenotypes including
      addictive behaviors, but none with alcohol dependence per se. METHODS: We
      analyzed a population of 134 patients with alcohol dependence, also assessing
      more homogeneous (severe) phenotypes, comparing this sample with a healthy
      control population, assessing two SNPs within the DRD1 gene in order to depict
      the role of DRD1 polymorphisms and haplotypes. RESULTS: The T allele of the rs686
      polymorphism within DRD1 gene was significantly more frequent in patients with
      alcohol dependence (p = 0.0008), with a larger excess for patients with severe
      dependence (p = 6 x 10(-6)), and even more for patients with severe complications
      such as withdrawal seizures (p = 7 x 10(-7)). A specific haplotype rs686*T
      rs4532*G within the DRD1 gene was significantly more precisely associated with
      alcohol dependence in our sample (p = 5 x 10(-6)). CONCLUSIONS: Even though
      chance finding cannot be ruled out, convergent evidence is given that the DRD1
      gene is a susceptibility gene in alcohol dependence, regarding the fact that
      relying on more homogeneous phenotypes (i.e., more severe patients) and more
      informative genetic markers (i.e., haplotypes) reinforce the initial association.

PMID- 18341653
TI  - Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF
      kappaB/cyclin D1 pathway and facilitates tumor growth.
AB  - Recent research indicates that inflammatory factors play important roles in the
      initiation and progression of cancers, including breast cancer.
      Daintain/allograft inflammatory factor-1 (AIF-1) is a crucial mediator in the
      inflammatory response, but it has not yet been reported whether daintain/AIF-1 is
      involved in the development of breast cancers. In this study, immunohistochemical
      analysis found strong positive expression of daintain/AIF-1 in breast ductal
      tumor epithelia, but only weakly positive or negative expression in the adjacent
      histologically normal ductal epithelia. Then, the effect of daintian/AIF-1 on the
      proliferation of the breast cancer cell line MDA-MB-231 was explored via
      transduction of the daintian/AIF-1 gene into the cells, and via inhibition of the
      expression of daintain/AIF-1 through short interference RNA. The results
      demonstrated that up-regulation and down-regulation of daintain/AIF-1 expressions
      promoted and inhibited the proliferation of MDA-MB-231, respectively. More
      interestingly, daintain/AIF-1 overexpression facilitated tumor growth in female
      nude mice. Furthermore, we found that daintain/AIF-1 overexpression up-regulated
      the expression of cyclin D1 and enhanced the transcriptional activity of nuclear
      factor-kappa B (NF-kappaB), a regulator of cyclin D1 expression. In contrast, the
      down-regulation of daintain/AIF-1 expression decreased cyclin D1 expression and
      inhibited the transcriptional activity of NF-kappaB. These results strongly
      suggest that daintain/AIF-1 can promote the growth of breast tumors via
      activating NF-kappaB signaling, which consequently up-regulates the expression of
      cyclin D1, implying that daintain/AIF-1 may be a novel target molecule for the
      prognosis and therapy of breast cancer.

PMID- 18341654
TI  - Both CD4+ and CD8+ T cell epitopes fused to heat shock cognate protein 70 (hsc70)
      can function to eradicate tumors.
AB  - Vaccination with heat shock proteins (HSP) protects mice from challenge with the
      tumor from which the HSP were isolated. The antigenicity of HSP vaccination is
      thought to result from HSP-associated endogenous major histocompatibility complex
      class I peptides or their precursors. The vaccination effect can be achieved in
      an adjuvant-free manner and is mediated by CD8(+) T cells, indicating that HSP
      can act as a natural adjuvant and cross-prime T cells in vivo. We previously
      devised a recombinant vaccine composed of a CD8(+) T cell epitope fused to the
      carboxyl-terminus of hsc70 and demonstrated efficient generation of antigen
      specific cytotoxic T lymphocyte (CTL) after vaccination with a few micrograms of
      the hsc70-CTL epitope fusion protein. The present study aimed to determine if the
      fusion protein vaccine could control tumor growth in vivo and whether
      simultaneous fusion of a CD4(+) T cell epitope to the amino terminus of the hsc70
      CTL epitope would be a more potent vaccine compared to the CTL epitope alone.
      Ovalbumin (OVA)-derived 8 mer peptide, OVA(257-264), and 16mer peptide, OVA(265
      280), were used as CD8(+) and CD4(+) T cell epitopes, respectively. Vaccination
      with hsc70-OVA(257-264) generated peptide specific CTL more effectively than a
      peptide plus incomplete Freund's adjuvant combination, and suppressed growth of
      OVA expressing EL4 (E.G7) and B16 melanoma tumor cells. Addition of OVA(265-280)
      to the amino-terminus of hsc70-OVA(257-264) (OVA(265-280)-hsc70-OVA(257-264))
      enhanced the generation of the OVA(257-264)-specific CTL population, leading to
      better eradication of MO5 lung metastasis compared to hsc70-OVA(257-264). Our
      results suggest that fusion of both CD4(+) and CD8(+) T cell epitopes to hsc70
      enhances tumor immunity beyond the effect of the CD8(+) T cell epitope alone.

PMID- 18341655
TI  - In vitro and clinical immunomodulatory effects of a novel Pentaherbs concoction
      for atopic dermatitis.
AB  - BACKGROUND: Our group recently reported a randomized and placebo-controlled
      clinical trial on the efficacy of a twice-daily concoction of five herbal
      ingredients (Pentaherbs formulation, PHF) in treating children with atopic
      dermatitis (AD). OBJECTIVES: To investigate the immunomodulatory effects that may
      be induced by PHF treatment. METHODS: We investigated the effects of PHF on
      cytotoxicity and proliferation of phytohaemagglutinin (PHA)- and staphylococcal
      enterotoxin B (SEB)-stimulated peripheral blood mononuclear cells (PBMC) isolated
      from buffy coat of blood donors. PHF-induced immunomodulation for five
      inflammatory mediators in cultured PBMC was measured by reverse transcription
      polymerase chain reaction and enzyme-linked immunosorbent assay. The effects of a
      3-month, open-label study of PHF on circulating inflammatory mediators in
      children with AD were also assessed. RESULTS: PHF at up to 1 mg mL(-1) dose
      dependently suppressed PBMC proliferation. The addition of PHF to cultured PBMC
      reduced supernatant concentrations of brain-derived neurotrophic factor (BDNF),
      interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha in response to PHA,
      and BDNF and thymus and activation-regulated chemokine (TARC) following SEB
      stimulation. PHF increased epithelial cell-derived neutrophil activating peptide
      78 levels in culture supernatants. At the RNA level, PHF suppressed the
      transcription of BDNF, TARC, IFN-gamma and TNF-alpha. Twenty-eight children with
      AD were treated with PHF for 3 months, and their mean plasma concentrations of
      BDNF and TARC decreased significantly from 1798 pg mL(-1) and 824 pg mL(-1) at
      baseline to 1378 pg mL(-1) and 492 pg mL(-1) (P = 0.002 and 0.013, respectively)
      upon study completion. CONCLUSIONS: PHF possesses in vitro and in vivo
      immunomodulatory properties that may mediate the clinical efficacy observed in AD
      treatment.

PMID- 18341656
TI  - Dermoscopy of fully regressive cutaneous melanoma.
AB  - BACKGROUND: Metastatic melanoma of unknown origin is a difficult challenge
      diagnostically and therapeutically. Diagnosis of the putative primary lesion is
      difficult. This difficulty increases when the primary lesion has undergone
      complete regression. OBJECTIVE: To define the dermoscopic features of fully
      regressed melanoma. PATIENTS AND METHODS: A single-institution, register-based
      study of an unselected consecutive series of seven cases of metastatic melanoma
      in the lymph nodes with no known or visible primary lesion was carried out. Skin
      examination included dermoscopy; when a suspicious area was found, observed
      dermoscopic features were recorded and a biopsy was performed. Diagnosis of
      completely regressive cutaneous melanoma was based on clinical-pathological
      correlation according to widely accepted criteria. RESULTS: Seven dermoscopic
      features were associated with completely regressive melanoma: scar-like
      depigmentation (100%); pink coloration of the background (100%); linear-irregular
      vessels (86%); globular pattern of the vessels (43%); remnants of pigmentation
      (86%), either macular (43%) or with a peppering aspect (43%); and white lighter
      transverse bands (43%). The last feature was only observed with polarized light
      dermoscopy devices. CONCLUSION: Dermoscopy more accurately distinguishes the
      vascular, pigmentary and scarring changes of fully regressive melanoma. We
      believe that dermoscopy should be included in the search for a regressive primary
      lesion in case of metastatic melanoma of unknown origin.

PMID- 18341657
TI  - Antinuclear antibodies in patients with polymorphic light eruption: a long-term
      follow-up study.
AB  - BACKGROUND: Previous studies have shown elevated titres of antinuclear antibodies
      (ANA) in 2.9-19% of patients with polymorphic light eruption (PLE). A diagnosis
      of lupus erythematosus (LE) was finally established in some of these ANA-positive
      patients. OBJECTIVES: To investigate whether the presence of ANA in patients with
      PLE merely represents an epiphenomenon or is associated with an increased risk of
      eventual progression to LE. METHODS: We identified 472 patients with PLE who had
      received prophylactic photo(chemo)therapy between 1986 and 2003 and were
      routinely tested for the presence of ANA. All ANA-positive (ANA titre of>or=1:80)
      patients were asked to attend for a follow-up examination comprising a medical
      history, complete skin inspection and a detailed laboratory analysis including
      ANA and antibodies against extractable nuclear antigens. RESULTS: Of all the
      patients, 55 (11.7%) were found to be ANA positive on one or several occasions,
      and three (0.6%) also had antibodies to SS-A/Ro. Thirty-nine (71%) of all ANA
      positive patients including all Ro+ subjects were available for follow-up after a
      median follow-up period of 8 years (interquartile range 5-11.5). Twenty-five
      patients showed persistence of ANA positivity with a median titre of 1:160 (range
      1:80-1:640), whereas in 14 patients ANA titres had returned to normal levels.
      None of the patients revealed additional clinical, histopathological or
      laboratory abnormalities suggestive of LE. CONCLUSIONS: After a median follow-up
      period of 8 years none of the ANA-positive patients developed LE. Our findings
      indicate that PLE is a benign disease without tendency to progress to LE.

PMID- 18341658
TI  - Activated status of basophils in chronic urticaria leads to interleukin-3 hyper
      responsiveness and enhancement of histamine release induced by anti-IgE stimulus.
AB  - BACKGROUND: Basophils and mast cells are the main target cells in chronic
      idiopathic urticaria (CIU). Besides the basopenia, intrinsic defects of the anti
      IgE cross-linking signalling pathway of basophils have been described in CIU.
      OBJECTIVES: We sought to investigate the profile of expression of activation
      markers on basophils of patients with CIU and to explore the effect of
      interleukin (IL)-3 priming upon anti-IgE cross-linking stimuli through expression
      of activation markers and basophil histamine releasability. METHODS: Evaluation
      of the surface expression of FcepsilonRIalpha, CD63, CD203c and CD123 on whole
      blood basophils of patients with CIU undergoing autologous serum skin test (ASST)
      was performed by flow cytometry. The effect of pretreatment with IL-3 in the anti
      IgE response was analysed by the expression of basophil activation markers and
      histamine release using enzyme-linked immunosorbent assay. RESULTS: Blood
      basophils of patients with CIU were reduced in number and displayed increased
      surface expression of FcepsilonRIalpha, which was positively correlated with the
      IgE serum levels. Upregulation of expression of both surface markers CD203c and
      CD63 was verified on basophils of patients with CIU, regardless of ASST response.
      High expression of IL-3 receptor on basophils was detected only in ASST+ patients
      with CIU. Pretreatment with IL-3 upregulated CD203c expression concomitantly with
      the excreting function of blood basophils and induced a quick hyper
      responsiveness to anti-IgE cross-linking on basophils of patients with CIU
      compared with healthy controls. CONCLUSIONS: Basophils of patients with CIU
      showed an activated profile, possibly due to an in vivo priming. Functionally,
      basophils have high responsiveness to IL-3 stimulation, thereby suggesting that
      defects in the signal transduction pathway after IgE cross-linking stimuli are
      recoverable in subjects with chronic urticaria.

PMID- 18341659
TI  - Cutaneous graft-versus-host-like histology in childhood. Importance of clonality
      analysis in differential diagnosis. A case report.

PMID- 18341660
TI  - Method of assessing involved facial areas: rule of fours.
AB  - BACKGROUND: Disease extent or affected area is probably the most easily and most
      frequently measured index of patient disability in dermatological disorders such
      as psoriasis. However, no standard method is available for assessing involved
      facial areas. OBJECTIVES: To devise a method for assessing involved facial areas
      and to examine its validity and reliability. METHODS: In study 1, the facial
      areas of 26 healthy adults were analysed and a new method for assessing facial
      areas was devised. In study 2, the validity and reliability of the devised method
      were investigated by 10 dermatologists using 30 photographs of patients with
      facial psoriasis. RESULTS: In study 1, facial regions were defined to have
      percentage areas that were multiples of 4% of the total facial area (which we
      refer to as the rule of fours), i.e. forehead 24%, one cheek 20%, perioral area
      8%, one aspect of an ear 4%, one periorbital area 4%, and nose 4%. In study 2, a
      comparison of values obtained using the rule of fours with those obtained using
      an image analysis system showed excellent intrarater and inter-rater reliability
      when using the rule of fours. CONCLUSIONS: The rule of fours is useful for
      assessing involved facial areas. The application of this rule was found to
      provide an accurate and reliable method as compared with image analysis.

PMID- 18341661
TI  - Nicorandil and ulcerations: a NAD/NADP and nicotinic acid-dependent side-effect?

PMID- 18341662
TI  - Ethnicity and other risk factors for acute lower limb cellulitis: a U.K.-based
      prospective case-control study.
AB  - BACKGROUND: Acute lower limb cellulitis is a common yet potentially serious
      condition. Previous studies have identified risk factors in the non-U.K.
      population. Ethnicity has been postulated as a possible risk factor but has not
      previously been investigated. OBJECTIVES: To identify risk factors for acute
      lower limb cellulitis in the U.K. population. METHODS: One hundred and fifty
      consecutive patients with cellulitis requiring hospital admission and 300
      controls were recruited to this prospective case-control study. Controls were
      matched for age and sex. RESULTS: Strongly predictive risk factors for acute
      lower limb cellulitis in the U.K. include being of white ethnicity and preceding
      episodes of injury to the affected leg. No systemic illnesses were identified as
      increasing an individual's risk of presenting with cellulitis. CONCLUSIONS: This
      study has identified that patients of white ethnicity are at higher risk of
      developing acute lower limb cellulitis compared with other ethnic groups. The
      importance of local risk factors has also been shown in the U.K. population.

PMID- 18341663
TI  - Multicentre intraindividual randomized trial of topical methyl aminolaevulinate
      photodynamic therapy vs. cryotherapy for multiple actinic keratoses on the
      extremities.
AB  - BACKGROUND: Methyl aminolaevulinate-photodynamic therapy (MAL-PDT) is an
      effective treatment in facial/scalp actinic keratosis (AK). OBJECTIVES: The aims
      of this study were to compare efficacy, safety, cosmetic outcome and patient
      preference of MAL-PDT vs. cryotherapy in patients with AK at other locations.
      METHODS: A multicentre, controlled, randomized, open, intraindividual, right-left
      comparison was performed. Patients with nonhyperkeratotic AK were treated once
      with MAL-PDT and cryotherapy on either side of the body. At week 12, lesions
      showing noncomplete response were retreated. The primary efficacy variable was
      the lesion response at week 24. Investigator's assessment of cosmetic outcome,
      patient's preference in terms of cosmetic outcome and a patient preference
      questionnaire were also analysed at week 24. RESULTS: In total, of 121 patients
      with 1343 lesions (98% located on the extremities and the remainder on the trunk
      and neck) were included. Both treatments provided a high mean percentage
      reduction in lesion count at week 24 with significantly higher efficacy for
      cryotherapy: 78% for MAL-PDT and 88% for cryotherapy (P=0.002, per protocol
      population). Investigator's assessment of cosmetic outcome was significantly
      better for MAL-PDT than cryotherapy (P<0.001), 79% of lesions having an excellent
      cosmetic outcome with MAL-PDT vs. 56% with cryotherapy at week 24. The cosmetic
      outcome achieved by MAL-PDT compared with cryotherapy was also preferred by
      patients (50% vs. 22%, respectively, P<0.001), and 59% of patients would prefer
      to have any new lesions treated with MAL-PDT compared with 25% with cryotherapy
      (P<0.001). Both treatment regimens were safe and well tolerated. CONCLUSIONS: MAL
      PDT showed inferior efficacy for treatment of non-face/scalp AK compared with
      cryotherapy. However, both treatments showed high efficacy, and MAL-PDT conveyed
      the advantages of better cosmesis and higher patient preference.

PMID- 18341664
TI  - Efficacy and safety of retapamulin ointment as treatment of impetigo: randomized
      double-blind multicentre placebo-controlled trial.
AB  - BACKGROUND: Impetigo is a common skin infection, primarily caused by
      Staphylococcus aureus and mainly occurring in children. It is usually treated
      topically with antibiotics to achieve a quick cure and prevent spread of the
      infection. Worldwide, resistance rates of S. aureus against commonly used
      antibiotics are rising. Retapamulin belongs to a newly developed class of
      antibiotics for the treatment of uncomplicated skin infections. OBJECTIVES: Our
      aim was to compare the efficacy and safety of topical application of retapamulin
      ointment with topical placebo ointment in the treatment of primary impetigo.
      METHODS: In a randomized, double-blind, multicentre study, patients received
      either topical retapamulin ointment 1% twice daily for 5 days or topical placebo.
      Patients were enrolled into the study for 14 days and attended the clinic for
      three visits during which clinical and laboratory evaluations were performed.
      RESULTS: Two hundred and thirteen patients were randomized, with 139 evaluable
      patients in the retapamulin group and 71 in the placebo group. Based on the
      primary efficacy endpoint of clinical response after 7 days (intention to treat),
      retapamulin ointment was superior to placebo (success rate 85.6% vs. 52.1%;
      P<0.0001). Similar results were found in the per protocol analysis and in the
      subgroup of patients who had a pathogen isolated at baseline. The most common
      adverse effect, pruritus at the application site, was reported by 6% and 1% of
      patients in the retapamulin and placebo groups, respectively. CONCLUSIONS: This
      study shows that topical retapamulin is effective and safe in the treatment of
      primary impetigo, offering a new treatment option.

PMID- 18341665
TI  - Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis:
      prevention of flare progression. A randomized controlled trial.
AB  - BACKGROUND: Previous studies suggested that early intervention with pimecrolimus
      cream 1% at the first signs and/or symptoms of a relapse of atopic dermatitis
      (AD) following remission may prevent the occurrence of more severe flares and
      therefore reduce corticosteroid exposure in the long term. However, this
      possibility was not rigorously evaluated. OBJECTIVES: To evaluate the
      effectiveness of pimecrolimus cream 1% for the prevention of flare progression in
      adults with AD. METHODS: A 26-week randomized controlled study was conducted in
      543 patients aged>or=18 years, with a history of mild or moderate AD, who were
      clear/almost clear of disease before randomization to pimecrolimus cream 1%
      (n=277) or matching vehicle cream (n=266). Twice-daily treatment with study
      medication was started at the onset of the first signs and/or symptoms of a
      relapse. If disease worsened, despite the application of study medication for at
      least 3 days, treatment with a moderately potent topical corticosteroid (TCS) was
      allowed in both groups. The primary efficacy endpoint was the number of days
      without TCS use for disease worsening. RESULTS: The mean number of TCS-free days
      was significantly higher (P<0.001) in the pimecrolimus cream 1% group (152 days)
      than in the vehicle cream group (138.7 days). In comparison with vehicle cream,
      pimecrolimus cream 1% reduced the mean number of flares requiring TCS use from
      1.39 to 0.97 (P=0.0014). Patients on pimecrolimus cream 1% made 30% fewer
      unscheduled visits (156) than patients on vehicle cream (223). CONCLUSIONS: In
      adults with a history of mild or moderate AD but free of active skin lesions,
      intervention with pimecrolimus cream 1% at the first signs and/or symptoms of a
      subsequent recurrence reduces the number of flares requiring TCS use and
      decreases the number of disease-related office visits.

PMID- 18341666
TI  - Polymorphisms in the PTPN22 region are associated with psoriasis of early onset.
AB  - BACKGROUND: Psoriasis, a chronic inflammatory skin disease, affects approximately
      2% of the population worldwide. Although the aetiology of psoriasis is poorly
      understood, patients with disease of early onset (Type I, age of onset<or=40
      years) usually have a strong genetic component to the disease. OBJECTIVES: The
      purpose of this study was to investigate the role of the protein tyrosine
      phosphatase nonreceptor type 22 (PTPN22) gene region in susceptibility to Type I
      psoriasis. PATIENTS AND METHODS: Thirteen single nucleotide polymorphisms (SNPs)
      mapping to the PTPN22 region were genotyped in 647 patients with Type I psoriasis
      and 566 normal controls. RESULTS: The rs2476601 (R620W) SNP, widely associated
      with other inflammatory autoimmune diseases, showed no evidence of association
      with susceptibility to Type I psoriasis. Two SNPs (rs1217414 and rs3789604)
      demonstrated significant association with Type I psoriasis and were subsequently
      genotyped in a further 253 unrelated patients and 2024 normal controls. rs1217414
      and rs3789604 were also significantly associated with Type I psoriasis in the
      combined datasets (P=0.003 and P=0.0002, respectively); furthermore carriage of
      both risk alleles was also significantly associated (P=0.002). CONCLUSIONS: This
      study demonstrates evidence of association of two SNPs (rs1217414 and rs3789604)
      in the PTPN22 region with Type I psoriasis, providing evidence for a role of this
      gene in Type I psoriasis that is not conferred by the R620W variant previously
      associated with a number of inflammatory diseases.

PMID- 18341667
TI  - Noninvasive biophysical assessments of the efficacy of a moisturizing cosmetic
      cream base for patients with atopic dermatitis during different seasons.
AB  - BACKGROUND: The use of emollients is recommended for patients with atopic
      dermatitis (AD) to maintain improved condition. OBJECTIVES: To ascertain
      objectively the effectiveness of a moisturizing cream for patients with AD during
      different seasons. METHODS: We conducted clinical evaluations, noninvasive
      biophysical measurements and biochemical analyses of the stratum corneum (SC)
      components of the volar forearm skin of 23 patients with AD after a moisturizer
      was applied twice daily for 4 weeks. The moisturizer was formulated according to
      the consensus of cosmetic scientists belonging to major Japanese cosmetic
      companies. The nontreated forearm served as a control. RESULTS: After using the
      moisturizer treatment, the hydration of the SC significantly increased together
      with a decrease in the desquamation measurements and an improvement in the
      regularity of skin surface corneocytes. An improvement was observed in the SC
      barrier function in winter, but was achieved only after 4 weeks in late spring
      during which time there even occurred exacerbation of skin conditions in three
      patients. With use of the moisturizer treatment, we found no change in the SC
      content of free amino acids or ceramides, the ratio of interleukin (IL)-1
      receptor antagonist to IL-1alpha, the ratio of immature to mature cornified
      envelopes, the size of the corneocytes or the emergence of parakeratotic cells in
      the skin surface corneocytes. CONCLUSION: Treatment with an adequate moisturizer
      is beneficial for the dry skin of patients with AD during the dry, cold season
      but it does not influence the impaired SC barrier function as effectively in the
      less arid season.

PMID- 18341668
TI  - Variability in the pharmacokinetics of intravenous busulphan given as a single
      daily dose to paediatric blood or marrow transplant recipients.
AB  - AIM: To examine inter- and intrapatient variability in the pharmacokinetics of
      intravenous (i.v.) busulphan given as a single daily dose to children with
      malignant (n = 19) and nonmalignant (n = 21) disease. METHODS: Busulphan (120 mg
      m(-2), 130 mg m(-2) or 3.2 mg kg(-1)) was administered over median 2.1 h. Blood
      samples (4-10) were collected after the first dose, busulphan concentrations were
      measured and pharmacokinetic parameters, including clearance (CL) and area under
      the concentration-time curve (AUC), were determined using the Kinetica software
      (Innaphase). Interpatient variability was assessed as percent coefficient of
      variation (% CV). Intrapatient variability was assessed by calculating percent
      differences between observed full dose AUC and AUC predicted from an initial 65
      mg m(-2) dose in 13 children who had busulphan pharmacokinetic monitoring.
      RESULTS: Clearance of i.v. busulphan in 40 children was 4.78 +/- 2.93 l h(-1) (%
      CV 61%), 0.23 +/- 0.08 l h(-1) kg(-1) (% CV 35%) and 5.79 +/- 1.59 l h(-1) m(-2)
      (% CV 27%). Age correlated significantly (p < 0.001) with CL (l h(-1)) and CL (l
      h(-1) kg(-1)), but not with CL (l h(-1) m(-2)). AUC normalized to the 130 mg m(
      2) dose ranged from 14.1 to 56.3 mg l(-1) x h (% CV 37%) and also did not
      correlate with age. Interpatient variability in CL (l h(-1) m(-2)) was highest in
      six children with immune deficiencies (60%) and lowest in seven children with
      solid tumours (14%). Intrapatient variability was <13% for nine (of 13) children,
      but between 20 and 44% for four children. CONCLUSIONS: There is considerable
      inter- and intrapatient variability in i.v. busulphan CL (l h(-1) m(-2)) and
      exposure that is unrelated to age, especially in children with immune
      deficiencies. These results suggest that monitoring of i.v. busulphan
      pharmacokinetics is required.

PMID- 18341669
TI  - An unusual systemic reaction associated with topical salicylic acid in a
      paediatric patient.

PMID- 18341670
TI  - Impact of CYP3A5 genetic polymorphism on pharmacokinetics of tacrolimus in
      healthy Japanese subjects.

PMID- 18341671
TI  - Absence of respiratory effects with ivabradine in patients with asthma.
AB  - AIM: beta-Blockers are commonly prescribed for stable angina and are recommended
      as initial therapy. However, beta-blockers are contraindicated in patients with
      obstructive airway disease because of a risk of bronchoconstriction. Ivabradine
      is a specific heart rate-lowering agent that acts via I(f) pacemaker channels in
      the sinoatrial node with no beta-adrenoreceptor activity. Ivabradine has been
      recently approved for the treatment of stable angina. This study assessed the
      effects of repeated administration of ivabradine on lung function in patients
      with asthma. METHODS: In this double-blind, placebo-controlled, crossover study,
      20 subjects with asthma received either oral ivabradine 10 mg b.i.d. or placebo
      for 4.5 days. Forced expiratory volume in 1 s (FEV(1)) and peak expiratory flow
      rate (PEFR) were designated as the main outcome variable. Diary cards were used
      to monitor asthma symptoms on a five-point scale, rescue medication usage, and
      adverse events. RESULTS: There were no significant differences in mean variation
      of FEV(1) (ivabradine P = 0.664; placebo P = 0.652) or PEFR (ivabradine P =
      0.153; placebo P = 0.356) from baseline following administration of ivabradine.
      There was also no significant difference in maximum percent variation in FEV(1)
      or PEF between treatment groups (P = 0.994; FEV(1) and P = 0.704; PEF). On a
      similar note, there was no significant difference in asthma symptoms or rescue
      medication usage reported between the two groups. Adverse events were generally
      mild-to-moderate in intensity and no cardiovascular or serious adverse events
      were recorded. CONCLUSIONS: This study confirms that ivabradine does not affect
      respiratory function or symptoms in patients with asthma and therefore represents
      a valuable therapeutic alternative to beta-blockers for treating patients with
      stable angina and asthma.

PMID- 18341672
TI  - Candidate mechanisms for capecitabine-related hand-foot syndrome.
AB  - AIMS: The oral fluoropyrimidine prodrug capecitabine is widely used in oncology.
      Capecitabine was designed to generate 5FU via the thymidine phosphorylase (TP)
      enzyme, preferentially expressed in tumoral tissues. Hand-foot syndrome (HFS) is
      a limiting toxicity of capecitabine. A pilot study on healthy volunteers was
      conducted in order to test the hypothesis that the occurrence of HFS could be
      related to tissue-specific expression of drug-metabolizing enzymes in the skin of
      the palm and sole. To this end, the expression of TP (activating pathway),
      dihydropyrimidine dehydrogenase (DPD, catabolic pathway) and cell proliferation
      (Ki67) were measured in the skin of the palm (target tissue for HFS) and of the
      lower back (control area). METHODS: Two paired 4-mm diameter punch biopsy
      specimens (palm and back) were taken in 12 healthy volunteers.
      Immunohistochemical analyses were performed on frozen tissues. RESULTS:
      Proliferation rate (Ki67 staining) was significantly higher in epidermal basal
      cells of the palm compared with the back (P = 0.008). Also, TP and DPD expression
      were significantly greater in the palm relative to the back (P = 0.039 and 0.012,
      respectively). TP and Ki67 expression were positively and significantly
      correlated in the palm. CONCLUSIONS: The high proliferation rate of epidermal
      basal cells in the palm could make them more sensitive to the local action of
      cytotoxic drugs. TP-facilitated local production of 5FU in the palm during
      capecitabine treatment could explain the occurrence of HFS. This observation may
      support future strategies to limit the occurrence of HFS during capecitabine
      therapy.

PMID- 18341673
TI  - The pharmacokinetics, CNS pharmacodynamics and adverse event profile of
      brivaracetam after multiple increasing oral doses in healthy men.
AB  - AIMS: Brivaracetam is a novel synaptic vesicle protein 2A ligand that has shown
      potent activity in animal models of epilepsy. This study examined the
      pharmacokinetics, central nervous system pharmacodynamics and adverse event
      profile of multiple oral doses of brivaracetam in healthy male subjects. METHODS:
      Three successive panels of 12 healthy male subjects received double-blind
      brivaracetam 200, 400 or 800 mg day(-1) (all doses well above the expected
      therapeutic range) or placebo (9 : 3), in two divided doses, for 14 days.
      RESULTS: Brivaracetam was rapidly absorbed (t(max) approximately 2 h) and
      eliminated (t(1/2) 7-8 h). Volume of distribution was slightly lower than total
      body water. A small fraction of the dose (5-8%) was excreted unchanged in urine
      together with significant levels of metabolites, suggesting predominantly
      metabolic clearance. Based on 6-beta-hydroxycortisol/cortisol ratios in urine,
      there was no evidence of induction of CYP3A4 activity. Saliva and plasma
      brivaracetam levels were highly correlated. Adverse events were mostly mild to
      moderate, central nervous system-related and resolved within the first day of
      treatment. No clinically relevant changes were observed in laboratory tests,
      vital signs, physical examinations or ECGs. Pharmacodynamic tests showed dose
      related sedation and decreased alertness that only persisted at 800 mg daily.
      CONCLUSIONS: Brivaracetam was well tolerated by healthy male volunteers at doses
      of 200-800 mg daily for 2 weeks, well above the expected clinically effective
      dose range. Brivaracetam had a favourable pharmacokinetic profile in this
      population, characterized by rapid absorption, volume of distribution limited to
      total body water, apparent single-compartment elimination and dose
      proportionality.

PMID- 18341674
TI  - The Dutch model for clinical pharmacology: collaboration between physician- and
      pharmacist--clinical pharmacologists.

PMID- 18341675
TI  - Phosphodiesterase 4 inhibitors in chronic obstructive pulmonary disease: a new
      approach to oral treatment.
AB  - Chronic obstructive pulmonary disease represents a major global health care
      burden for both primary and secondary care providers and is the most common
      respiratory condition necessitating hospital admission. Short-acting
      bronchodilators play a vital role in immediate relief of symptoms, while inhaled
      long-acting bronchodilators and inhaled corticosteroids are advocated for regular
      use in individuals with persistent symptoms and exacerbations. Theophylline is a
      nonspecific phosphodiesterase inhibitor and is usually reserved for patients with
      ongoing symptoms despite optimum inhaled bronchodilator treatment or when
      difficulty is encountered with inhaler devices. However, it is often not widely
      used mainly due to frequency of dose-related adverse effects, numerous drug
      interactions and narrow therapeutic index. This in turn has lead to the
      development of more selective phosphodiesterase inhibitors in an attempt to
      create a drug which patients can use with beneficial effects but without the
      problems associated with theophylline. Current data do indicate that
      phosphodiesterase 4 inhibitors confer some benefits in chronic obstructive
      pulmonary disease when compared to placebo in terms of lung function, quality of
      life and exacerbations. They are also generally well tolerated. Further studies
      are required to determine fully their long-term beneficial and adverse effect
      profiles and ultimately where they might comfortably sit in management
      algorithms.

PMID- 18341676
TI  - Respirable dose delivery of fluticasone propionate from a small valved holding
      chamber, a compact breath actuated integrated vortex device and a metered dose
      inhaler.
AB  - AIMS: To compare the respirable dose delivery of the hydrofluroalkane fluticasone
      propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a
      Synchro-Breathe (SB) device, and pMDI Evohaler (EH). METHODS: Seventeen mild to
      moderate asthmatics completed the study using a randomized, double-blind, double
      dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were
      administered via the EH, AP, and SB devices. The overnight urinary cortisol :
      creatinine ratio (OUCC) was measured at baseline and after each dose. RESULTS:
      Significant suppression of OUCC occurred from baseline with AP and SB but not EH
      devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P <
      0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37
      (equating to 68%, 45% and 9% falls, respectively). Significant differences in
      OUCC between devices were as follows: (geometric mean fold difference, 95% CI):
      AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P =
      0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37%
      differences, respectively). CONCLUSIONS: The use of an optimally prepared AP
      spacer and breath actuated SB device, when compared with pMDI, significantly
      increased the respirable dose of HFA-FP.

PMID- 18341677
TI  - A new formulation of tolevamer, a novel nonantibiotic polymer, is safe and well
      tolerated in healthy volunteers: a randomized phase I trial.
AB  - AIMS: To evaluate the safety and tolerability of a new oral solution formulation
      of tolevamer potassium sodium, a nonantibiotic polymer that binds Clostridium
      difficile toxins A and B. METHODS: This phase 1 randomized, double-blind, placebo
      controlled study evaluated four doses of tolevamer potassium sodium in 40 healthy
      volunteers using a sequential dose escalation paradigm and doses of 6, 9, 12 and
      15 g day(-1) for 9 days. Within each 10 patient cohort, eight patients received
      active treatment and two matching placebo. Placebo subjects were pooled to
      provide eight per arm. All subjects received three times daily dosing on days 2-8
      as well as a loading dose (a single dose equal to the total daily dose) either on
      day 1 or day 9. RESULTS: All 40 subjects completed the study per protocol.
      Treatment-emergent adverse events (TEAEs) were generally mild, transient, and
      resolved without sequelae. There were no serious AEs or deaths. There was no
      relationship detected between dose and the incidence of TEAEs, whether drug
      related (all gastrointestinal disorders) or not. No clinically significant
      changes in laboratory parameters, including serum and urinary potassium
      concentrations, vital signs, and results of physical examination, were observed.
      A small but statistically significant reduction in 24 h urine potassium excretion
      was seen in the 15 g day(-1) dose group, and on day 10 in the 6 g day(-1) group.
      CONCLUSIONS: Tolevamer oral solution administered for 9 days at total daily doses
      up to 15 g, with loading doses of up to 15 g, was generally safe and well
      tolerated in healthy volunteers.

PMID- 18341678
TI  - Eprosartan modulates the reflex activation of the sympathetic nervous system in
      sodium restricted healthy humans.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: A sympatho-inhibitory effect of ACE
      inhibitors and AT(1) receptor antagonists has been widely demonstrated in animal
      models, but in humans this effect tends only to be present during chronic
      treatment in conditions with pre-existing high levels of sympathetic activity.
      Sodium restriction increases renal sympathetic nerve activity and the activity of
      the renin-angiotensin system and may be a favourable condition to demonstrate
      sympatho-inhibition as a short-term effect of the AT(1) receptor antagonist
      eprosartan in healthy humans. WHAT THIS STUDY ADDS: Results from our study
      indicate that during sodium restriction eprosartan has a small inhibitory effect
      on nonbaroreflex mediated activation of the sympathetic nervous system. During
      arterial baroreflex mediated activation of the sympathetic nervous system this
      effect is, however, completely overruled by an increased sensitivity of the
      arterial baroreflex. AIMS To test the hypothesis that eprosartan inhibits both
      nonbaroreflex and arterial baroreflex mediated activation of the sympathetic
      nervous system, assessed by renal tubular function, systemic haemodynamics and
      vasoactive hormones, in sodium restricted healthy humans. METHODS: The effect of
      eprosartan on urinary sodium, lithium and water excretion, heart rate (HR), blood
      pressure and vasoactive hormones was measured before, during and after a cold
      pressor test (CPT) and sodium nitroprusside (SNP) infusion in a randomized,
      placebo controlled, double-blind, crossover study in 17 healthy subjects.
      Glomerular filtration rate and renal tubular function were determined by a
      continuous infusion clearance technique and vasoactive hormones by
      radioimmunoassays. RESULTS: Eprosartan attenuated the impact of the CPT on HR
      (mean difference from placebo (95% confidence interval) (3.9 (0.7, 7.0) min(-1))
      and mean arterial pressure (MAP) (4.7 (0.3, 9.2) mmHg), but no effect of
      eprosartan was observed on the impact of the CPT on renal tubular function.
      During a SNP induced reduction in MAP of 10 mmHg eprosartan decreased fractional
      excretions of sodium (0.46 (0.14, 0.76)%) and lithium (5.1 (2.5, 7.6)%) and
      tended to increase HR (4.1 (-0.26, 8.4) min(-1)) and plasma concentrations of
      norepinephrine (33.8 (-5.8, 72.1) pg ml(-1)). CONCLUSIONS; These findings suggest
      that during mild sodium restriction eprosartan has a small inhibitory effect on
      nonbaroreflex mediated activation of the sympathetic nervous system. During
      arterial baroreflex mediated activation of the sympathetic nervous system this
      effect is, however, completely overruled by an increased sensitivity of the
      arterial baroreflex.

PMID- 18341679
TI  - Clinically informative measures of the effect of drugs or other interventions.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Several comparative measures (ratios,
      differences, or the number needed to treat) are used to express the effect of a
      drug or another intervention. These measures can vary in the way they are
      affected by the background risk measured from the reference group. WHAT THIS
      STUDY ADDS: This paper reviews the formulation, interpretation and limitations of
      measures of effect. We describe a little-known parameter, the attained effect or
      clinical result ratio, a positive reformulation of the relative risk difference,
      and suggest how available parameters can be best used to summarize results of
      studies of the effect of drugs. AIMS Measures to compare two drugs are often
      affected by the background risk in the reference group; a ceiling effect results
      when the background risk is small. We review measures of the effect of drugs,
      including a special formulation of the relative risk difference, the attained
      effect or clinical result ratio, that addresses background risk and ceiling
      effect. METHODS: Existing measures are the risk and odds ratios, the absolute and
      relative risk differences, and the number needed to treat. The attained effect is
      defined as the observed gain in success (the difference of proportion of success
      between the two interventions), divided by the maximum attainable gain, the
      maximum proportion of success one can expect. We illustrate the relationship
      between these measures with published results of two meta-analyses. RESULTS: In
      studies of the effectiveness of cell salvage, the baseline risk ranged between 8
      and 95%. This variability affected the risk difference and number needed to
      treat, while the attained effect, with a ceiling residual risk of 2%, showed that
      the gain in success was half the maximum attainable gain. In studies of the
      effectiveness of therapy in patients infected by the human immunodeficiency
      virus, where the baseline risk was less variable, and there was no ceiling
      effect, the maximum attained effect indicated that the gain could be much
      smaller. CONCLUSION: The attained effect, interpreted as the proportion of
      effectiveness that remains to gain for future interventions, can usefully
      complete the number needed to treat as a clinically informative effect measure.

PMID- 18341680
TI  - Human pharmacology of a performance-enhancing dietary supplement under resting
      and exercise conditions.
AB  - WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Performance-enhancing dietary
      supplements have not been clinically tested for safety or efficacy. In clinical
      trials performed under resting conditions, performance-enhancing supplements
      raise blood pressure and affect glucose homeostasis. The effect of exercise on
      the pharmacokinetics and pharmacodynamics of stimulant herbals is unknown. WHAT
      THIS STUDY ADDS: Supplement-induced effects on blood pressure and glucose levels
      are not ameliorated by exercise. Exercise does not affect the kinetics of
      stimulant ingredients, caffeine and synephrine. Performance-enhancing supplement
      use modestly improves exercise tolerance. AIMS Dietary supplements (DS) promoted
      to enhance athletic performance often contain herbal sympathomimetics such as
      Citrus aurantium (synephrine) and caffeine. We aimed to characterize the
      pharmacology of a performance-enhancing DS in the setting of exercise. METHODS:
      Ten healthy adults (three women) aged 20-31 years participated in a three-arm,
      double-blind, placebo-controlled, crossover study. Subjects ingested one dose of
      DS (Ripped Fuel Extreme Cut(R) with 21 mg synephrine and 304 mg caffeine by
      analysis) under resting conditions and 1 h prior to moderately intense exercise
      (30 min on cycle ergometer at 75-80% HR(max)), with a placebo (PLC)/exercise
      control. Plasma synephrine and caffeine concentrations were measured over 12 h,
      and vital signs, serum electrolytes, oxygen consumption and perceived exercise
      exertion were monitored. RESULTS: No significant adverse events occurred.
      Synephrine and caffeine pharmacokinetics were unaffected by exercise. Post
      exercise diastolic blood pressure was higher after DS (peak mean 71.7 +/- 8.7
      mmHg) than PLC (63.0 +/- 4.9 mmHg) (p = 0.007). There were no substantial
      treatment-related differences in post-exercise HR, systolic blood pressure, or
      temperature. Postprandial plasma glucose increased to 121.0 +/- 31.6 mg dl(-1)
      with DS and exercise vs. 103.7 +/- 25.5 mg dl(-1) with PLC and exercise (P =
      0.004). No treatment differences in exercise-related oxygen consumption, serum
      lactate, or insulin were observed. Exercise was rated less difficult with DS than
      PLC (P = 0.001). CONCLUSIONS: Blood pressure and plasma glucose increased post
      exercise with DS use, which could be detrimental in some people. Exercise was
      perceived as less strenuous after DS, presumably due to the stimulant effects of
      caffeine.

PMID- 18341681
TI  - Graft rejection: pharmacogenetic analysis or drug anamnesis?
AB  - AIMS: A 23-year-old Caucasian woman, with cystic fibrosis, bilateral lung
      transplantation and immunosuppressive therapy with prednisolone, tacrolimus and
      sirolimus, presented with clinical symptoms of a chronic transplant rejection.
      METHODS: Since constant sufficient blood level of tacrolimus and sirolimus had
      never been achieved, a genetic analysis was carried out to clarify drug
      metabolism. RESULTS: The genetic analysis for polymorphisms of cytochrome P450
      (CYP) 3A4,5,7 revealed no sequence alterations in the CYP 3A4,5,7 gene. Thus,
      drug intake was scrutinized in detail, disclosing a missing interval between the
      intake of both immunosuppressive agents. After a correct drug intake the woman's
      condition ameliorated and the blood levels reached normal range. CONCLUSIONS:
      This case report highlights the crucial importance of basic medical skills like
      an accurate and dainty drug anamnesis before high tech approaches were applied.

PMID- 18341682
TI  - Assessing general practitioners' prescribing behaviour in elderly patients with
      concealed renal failure.

PMID- 18341683
TI  - Asymptomatic idiopathic intracranial hypertension in children.
AB  - OBJECTIVE: To define characteristics of pediatric asymptomatic idiopathic
      intracranial hypertension (IIH). PATIENTS AND METHODS: We retrospectively
      reviewed our Neuro-Ophthalmology database (2000-2006) for all cases of
      symptomatic and asymptomatic pediatric IIH. RESULTS: Out of 45 IIH cases, 14
      (31.1%) were asymptomatic (incidental examination). When compared with children
      with symptomatic IIH, asymptomatic cases were younger [5.6 (1.8-15) vs 11.0 (5
      17) years, P = 0.007], had lower percentage of obesity (14.3% vs 48.4%, P =
      0.046), and had male predominance (71.4% vs 38.7%, P = 0.06). Asymptomatic cases
      required shorter duration of acetazolamide treatment [3 (0-8), vs 6 (0-20)
      months, P = 0.021], and resulted in complete resolution of swollen discs.
      CONCLUSIONS: We speculate that asymptomatic IIH may be more common in young
      children and could represent a milder form or a presymptomatic phase before
      evolving into classic symptomatic IIH. Further studies to assess the clinical
      significance of asymptomatic IIH are warranted.

PMID- 18341684
TI  - Hepatotoxicity associated with antiepileptic drugs.
AB  - BACKGROUND: Drug-induced liver injury associated with antiepileptic drugs (AED)
      is well recognized. The frequency of the most common AED is rare but the
      consequences can be very serious leading to death or liver transplantation due to
      acute liver failure induced by these drugs. CLINICAL FEATURES: Hypersensitivity
      features are found in more than 70% of patients with phenytoin-induced liver
      injury, whereas this is only observed in 30% of carbamazepine-associated
      hepatotoxicity and very rarely with valproate (VPA)-induced liver injury.
      PATHOPHYSIOLOGY: The underlying mechanisms behind hepatotoxicity induced by AED
      are not clear. Reactive metabolites from AED can, in some cases, lead to direct
      cytotoxicity and liver cell necrosis, whereas in other cases this may lead to
      neoantigen formation inducing immunoallergic mechanisms. TREATMENT: No specific
      therapy is of proved value in severe hepatotoxicity due to AED. However, N
      acetylcystein is an appropriate treatment in patients with clinically significant
      liver injury due to phenytoin and carbamazepine. In patients with VPA-associated
      liver injury, carnitine that is an important co-factor in the mitochondrial beta
      oxidation of fatty acids is the recommended treatment. Early referral of patients
      with severe liver reactions and coagulopathy to liver transplant centers before
      encephalopathy can be the difference between liver transplantation and death.

PMID- 18341685
TI  - Deceased organ donor characteristics and clinical interventions associated with
      organ yield.
AB  - While the function of each organ is used by each transplant team to assess
      suitability for transplantation, little is known about the donor characteristics
      and clinical interventions that contribute toward overall organ transplantation
      potential. We conduct a retrospective review of United Network for Organ Sharing
      (UNOS) deceased donor registry data from January 2005 to December 2006. This
      registry contains all deceased donors from whom organs were recovered during this
      time period (n = 15,601). Ordinary least-squares (OLS) regression models using
      variables in the registry are estimated to predict the number of organs
      transplanted. Outcome is the number of organs transplanted per donor. Organ yield
      is found to depend significantly on donor age, anoxia as cause of death, history
      of myocardial infarction (MI), hypertension and/or diabetes, body mass index
      (BMI), B or AB blood type, cocaine and/or cigarette use and hepatitis infection
      (p < 0.01). In addition, the clinical interventions of steroid administration,
      desmopressin (DDAVP) and diuretic usage, as well as oxygenation, are associated
      with organ yield. Both intrinsic donor characteristics and medical management
      practice are observed to be highly variable across organ procurement
      organizations (OPOs). These findings may provide important information to explore
      and assess the efficacy of clinical interventions, compare OPO performance and
      point to best practices.

PMID- 18341686
TI  - Transient depletion of dividing T lymphocytes in mice induces the emergence of
      regulatory T cells and dominant tolerance to islet allografts.
AB  - We previously showed that transient depletion of dividing T cells at the time of
      an allogeneic transplantation induces long-term tolerance to the allograft. Here
      we investigated the role of homeostatic perturbation and regulatory T cells
      (Treg) in such tolerance. Transient depletion of dividing T cells was induced at
      the time of an allogeneic pancreatic islets graft, by administration of
      ganciclovir for 14 days, into diabetic transgenic mice expressing a thymidine
      kinase (TK) conditional suicide gene in T cells. Allograft tolerance was obtained
      in 63% of treated mice. It was not due to global immunosuppression, permanent
      deletion or anergy of donor-alloantigens specific T cells but to a dominant
      tolerance process since lymphocytes from tolerant mice could transfer tolerance
      to naive allografted recipients. The transient depletion of dividing T cells
      induces a 2- to 3-fold increase in the proportion of CD4(+)CD25(+)Foxp3(+) Treg,
      within 3 weeks that persisted only in allograft-bearing mice but not in
      nongrafted mice. Tolerance with similar increased proportion of Treg cells was
      also obtained after a cytostatic hydroxyurea treatment in normal mice. Thus, the
      transient depletion of dividing T cells represents a novel means of immuno
      intervention based on disturbance of T-cell homeostasis and subsequent increase
      in Treg proportion.

PMID- 18341687
TI  - Efficacy of motor imagery in post-stroke rehabilitation: a systematic review.
AB  - BACKGROUND: Evaluation of how Motor Imagery and conventional therapy
      (physiotherapy or occupational therapy) compare to conventional therapy only in
      their effects on clinically relevant outcomes during rehabilitation of persons
      with stroke. DESIGN: Systematic review of the literature METHODS: We conducted an
      electronic database search in seven databases in August 2005 and also hand
      searched the bibliographies of studies that we selected for the review. Two
      reviewers independently screened and selected all randomized controlled trials
      that compare the effects of conventional therapy plus Motor Imagery to those of
      only conventional therapy on stroke patients. The outcome measurements were: Fugl
      Meyer Stroke Assessment upper extremity score (66 points) and Action Research Arm
      Test upper extremity score (57 points). Due to the high variability in the
      outcomes, we could not pool the data statistically. RESULTS: We identified four
      randomized controlled trials from Asia and North America. The quality of the
      included studies was poor to moderate. Two different Motor imagery techniques
      were used (three studies used audiotapes and one study had occupational
      therapists apply the intervention). Two studies found significant effects of
      Motor Imagery in the Fugl-Meyer Stroke Assessment: Differences between groups
      amounted to 11.0 (1.0 to 21.0) and 3.2 (-4 to 10.3) respectively and in the
      Action Research Arm Test 6.1 (-6.2 to 18.4) and 15.8 (0.5 to 31.0) respectively.
      One study did not find a significant effect in the Fugl-Meyer Stroke Assessment
      and Color trail Test (p = 0.28) but in the task-related outcomes (p > 0.001).
      CONCLUSION: Current evidence suggests that Motor imagery provides additional
      benefits to conventional physiotherapy or occupational therapy. However, larger
      and methodologically sounder studies should be conducted to assess the benefits
      of Motor imagery.

PMID- 18341688
TI  - Atypically distributed cutaneous lesions of Norwegian scabies in an HIV-positive
      man in South India: a case report.
AB  - INTRODUCTION: Immune-compromised subjects, especially those with underlying HIV
      disease, are prone to be infected with Norwegian scabies, where the cutaneous
      lesions are classically distributed over the extremities. CASE PRESENTATION: We
      report the case of an HIV-positive 16-year-old man with severe crusted Norwegian
      scabies initially misdiagnosed as a dermal fungal infection. The patient had
      extensive, generalized, thick, hyperkeratotic, crusting, yellowish papule lesions
      distributed on the entire body from his scalp to his toes.The patient was started
      with Ivermectin and topical Permethrin, which eventually resulted in complete
      resolution. Interestingly, despite quarantining efforts, one of the patient's
      acquaintances and a healthcare worker acquired the symptoms of itching.
      CONCLUSION: This atypical presentation of Norwegian scabies emphasizes the need
      to include scabies in the differential diagnosis when HIV-infected patients
      present with crusted, generalized cutaneous lesions.

PMID- 18341689
TI  - From multidimensional neuropsychological outcomes to a cognitive complication
      rate: the International Subarachnoid Aneurysm Trial.
AB  - BACKGROUND: The neuropsychological arm of the International Subarachnoid Aneurysm
      Trial (N-ISAT) evaluated the cognitive outcome of 573 patients at 12 months
      following subarachnoid haemorrhage (SAH). The assessment included 29 psychometric
      measures, yielding a substantial and complex body of data. We have explored
      alternative and optimal methodologies for analysing and summarising these data to
      enable the estimation of a cognitive complication rate (CCR). Any differences in
      cognitive outcome between the two arms of the trial are not however reported
      here. METHODS: All individual test scores were transformed into z-scores and a
      5th percentile cut-off for impairment was established. A principal components
      analysis (PCA) was applied to these data to mathematically transform correlated
      test scores into a smaller number of uncorrelated principal components, or
      cognitive 'domains'. These domains formed the basis for grouping and weighting
      individual patients' impaired scores on individual measures. In order to increase
      the sample size, a series of methods for handling missing data were applied.
      RESULTS: We estimated a 34.1% CCR in all those patients seen face-to-face, rising
      to 37.4% CCR with the inclusion of patients who were unable to attend assessment
      for reason related to the index SAH. This group demonstrated significantly more
      self and carer/relative rated disability on a Health Related Quality of Life
      questionnaire, than patients classified as having no functionally significant
      cognitive deficits. CONCLUSION: Evaluating neuropsychological outcome in a large
      RCT involves unique methodological and organizational challenges. We have
      demonstrated how these problems may be addressed by re-classifying interval data
      from 29 measures into a dichotomous CCR. We have presented a 'sliding scale' of
      undifferentiated individual cognitive impairments, and then on the basis of PCA
      derived cognitive 'domains', included consideration of the distribution of
      impairments in these terms. In order to maximize sample size we have suggested
      ways for patients who did not complete the entire protocol to be included in the
      overall CCR. ISAT TRIAL REGISTRATION: ISRCTN49866681.

PMID- 18341690
TI  - HPV type infection in different anogenital sites among HIV-positive Brazilian
      women.
AB  - OBJECTIVES: To evaluate the prevalence of human papillomavirus (HPV) types, and
      risk factors for HPV positivity across cervix, vagina and anus, we conducted a
      study among 138 women with human immunodeficiency virus (HIV). GOAL: Compare the
      prevalence of different HPV types and the risk factors for HPV positivity in
      three sites. RESULTS: The most frequently detected HPV types in all sites were,
      in decreasing order, HPV16, 53, 18, 61 and 81. Agreement between the cervix and
      vagina was good (kappa 0.60 - 0.80) for HPV16 and 53 and excellent (Kappa > 0.80)
      for HPV18 and 61. HPV positivity was inversely associated with age for all
      combinations including the anal site. CONCLUSION: In HIV positive women, HPV18 is
      the most spread HPV type found in combinations of anal and genital sites. The
      relationship of anal to genital infection has implications for the development of
      anal malignancies. Thus, the efficacy of the current HPV vaccine may be
      considered not only for the cervix, but also for prevention of HPV18 anal
      infection among immunossuppressed individuals.

PMID- 18341691
TI  - Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-alpha
      and dexamethasone.
AB  - BACKGROUND: CD38 is expressed in human airway smooth muscle (HASM) cells,
      regulates intracellular calcium, and its expression is augmented by tumor
      necrosis factor alpha (TNF-alpha). CD38 has a role in airway hyperresponsiveness,
      a hallmark of asthma, since deficient mice develop attenuated airway
      hyperresponsiveness compared to wild-type mice following intranasal challenges
      with cytokines such as IL-13 and TNF-alpha. Regulation of CD38 expression in HASM
      cells involves the transcription factor NF-kappaB, and glucocorticoids inhibit
      this expression through NF-kappaB-dependent and -independent mechanisms. In this
      study, we determined whether the transcriptional regulation of CD38 expression in
      HASM cells involves response elements within the promoter region of this gene.
      METHODS: We cloned a putative 3 kb promoter fragment of the human cd38 gene into
      pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of
      the putative cd38 promoter region revealed one NF-kappaB and several AP-1 and
      glucocorticoid response element (GRE) motifs. HASM cells were transfected with
      the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-kappaB and some
      of the AP-1 sites, or the promoter with mutations of the NF-kappaB and/or AP-1
      sites. Using the electrophoretic mobility shift assays, we determined the binding
      of nuclear proteins to oligonucleotides encoding the putative cd38 NF-kappaB, AP
      1, and GRE sites, and the specificity of this binding was confirmed by gel
      supershift analysis with appropriate antibodies. RESULTS: TNF-alpha induced a two
      fold activation of the 3 kb promoter following its transfection into HASM cells.
      In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF
      kappaB and/or AP-1 sites or in the presence of dexamethasone, there was no
      induction in the presence of TNF-alpha. The binding of nuclear proteins to
      oligonucleotides encoding the putative cd38 NF-kappaB site and some of the six AP
      1 sites was increased by TNF-alpha, and to some of the putative cd38 GREs by
      dexamethasone. CONCLUSION: The EMSA results and the cd38 promoter-reporter assays
      confirm the functional role of NF-kappaB, AP-1 and GREs in the cd38 promoter in
      the transcriptional regulation of CD38.

PMID- 18341692
TI  - Genome assembly forensics: finding the elusive mis-assembly.
AB  - We present the first collection of tools aimed at automated genome assembly
      validation. This work formalizes several mechanisms for detecting mis-assemblies,
      and describes their implementation in our automated validation pipeline, called
      amosvalidate. We demonstrate the application of our pipeline in both bacterial
      and eukaryotic genome assemblies, and highlight several assembly errors in both
      draft and finished genomes. The software described is compatible with common
      assembly formats and is released, open-source, at http://amos.sourceforge.net.

PMID- 18341693
TI  - Responding to infectious diseases in Burma and her border regions.

PMID- 18341694
TI  - Increase coverage of HIV and AIDS services in Myanmar.
AB  - Myanmar is experiencing an HIV epidemic documented since the late 1980s. The
      National AIDS Programme national surveillance ante-natal clinics had already
      estimated in 1993 that 1.4% of pregnant women were HIV positive, and UNAIDS
      estimates that at end 2005 1.3% (range 0.7-2.0%) of the adult population was
      living with HIV. While a HIV surveillance system has been in place since 1992,
      the programmatic response to the epidemic has been slower to emerge although
      short- and medium-terms plans have been formulated since 1990. These early plans
      focused on the health sector, omitted key population groups at risk of HIV
      transmission and have not been adequately funded. The public health system more
      generally is severely under-funded.By the beginning of the new decade, a number
      of organisations had begun working on HIV and AIDS, though not yet in a formally
      coordinated manner. The Joint Programme on AIDS in Myanmar 2003-2005 was an
      attempt to deliver HIV services through a planned and agreed strategic framework.
      Donors established the Fund for HIV/AIDS in Myanmar (FHAM), providing a pooled
      mechanism for funding and significantly increasing the resources available in
      Myanmar. By 2006 substantial advances had been made in terms of scope and
      diversity of service delivery, including outreach to most at risk populations to
      HIV. More organisations provided more services to an increased number of people.
      Services ranged from the provision of HIV prevention messages via mass media and
      through peers from high-risk groups, to the provision of care, treatment and
      support for people living with HIV. However, the data also show that this scaling
      up has not been sufficient to reach the vast majority of people in need of HIV
      and AIDS services.The operating environment constrains activities, but does not,
      in general, prohibit them. The slow rate of service expansion can be attributed
      to the burdens imposed by administrative measures, broader constraints on
      research, debate and organizing, and insufficient resources. Nevertheless,
      evidence of recent years illustrates that increased investment leads to more
      services provided to people in need, helping them to obtain their right to health
      care. But service expansion, policy improvement and capacity building cannot
      occur without more resources.

PMID- 18341695
TI  - Displacement and disease: The Shan exodus and infectious disease implications for
      Thailand.
AB  - Decades of neglect and abuses by the Burmese government have decimated the health
      of the peoples of Burma, particularly along her eastern frontiers, overwhelmingly
      populated by ethnic minorities such as the Shan. Vast areas of traditional Shan
      homelands have been systematically depopulated by the Burmese military regime as
      part of its counter-insurgency policy, which also employs widespread abuses of
      civilians by Burmese soldiers, including rape, torture, and extrajudicial
      executions. These abuses, coupled with Burmese government economic mismanagement
      which has further entrenched already pervasive poverty in rural Burma, have
      spawned a humanitarian catastrophe, forcing hundreds of thousands of ethnic Shan
      villagers to flee their homes for Thailand. In Thailand, they are denied refugee
      status and its legal protections, living at constant risk for arrest and
      deportation. Classified as "economic migrants," many are forced to work in
      exploitative conditions, including in the Thai sex industry, and Shan migrants
      often lack access to basic health services in Thailand. Available health data on
      Shan migrants in Thailand already indicates that this population bears a
      disproportionately high burden of infectious diseases, particularly HIV,
      tuberculosis, lymphatic filariasis, and some vaccine-preventable illnesses,
      undermining progress made by Thailand's public health system in controlling such
      entities. The ongoing failure to address the root political causes of migration
      and poor health in eastern Burma, coupled with the many barriers to accessing
      health programs in Thailand by undocumented migrants, particularly the Shan,
      virtually guarantees Thailand's inability to sustainably control many infectious
      disease entities, especially along her borders with Burma.

PMID- 18341696
TI  - An assessment of vulnerability to HIV infection of boatmen in Teknaf, Bangladesh.
AB  - BACKGROUND: Mobile population groups are at high risk for contracting HIV
      infection. Many factors contribute to this risk including high prevalence of
      risky behavior and increased risk of violence due to conflict and war. The Naf
      River serves as the primary border crossing point between Teknaf, Bangladesh and
      Mynamar [Burma] for both official and unofficial travel of people and goods.
      Little is known about the risk behavior of boatmen who travel back and forth
      between Teknaf and Myanmar. However, we hypothesize that boatmen may act as a
      bridging population for HIV/AIDS between the high-prevalence country of Myanmar
      and the low-prevalence country of Bangladesh. METHODS: Methods included initial
      rapport building with community members, mapping of boatmen communities, and in
      depth qualitative interviews with key informants and members from other
      vulnerable groups such as spouses of boatmen, commercial female sex workers, and
      injecting drug users. Information from the first three stages was used to create
      a cross-sectional survey that was administered to 433 boatmen. RESULTS: Over 40%
      of the boatmen had visited Myanmar during the course of their work. 17% of these
      boatmen had sex with CSW while abroad. There was a significant correlation found
      between the number of nights spent in Myanmar and sex with commercial sex
      workers.In the past year, 19% of all boatmen surveyed had sex with another man.
      14% of boatmen had participated in group sex, with groups ranging in size from
      three to fourteen people. Condom use was rare {0 to 4.7% during the last month},
      irrespective of types of sex partners. Regression analysis showed that boatmen
      who were 25 years and older were statistically less likely to have sexual
      intercourse with non- marital female partners in the last year compared to the
      boatmen aged less than 25 years. Similarly deep-sea fishing boatmen and non
      fishing boatmen were statistically less likely to have sexual intercourse with
      non- marital female partners in the last year compared to the day long fishing
      boatmen adjusting for all other variables. Boatmen's knowledge regarding HIV
      transmission and personal risk perception for contracting HIV was low.
      CONCLUSION: Boatmen in Teknaf are an integral part of a high-risk sexual
      behaviour network between Myanmar and Bangladesh. They are at risk of obtaining
      HIV infection due to cross border mobility and unsafe sexual practices. There is
      an urgent need for designing interventions targeting boatmen in Teknaf to combat
      an impending epidemic of HIV among this group. They could be included in the
      serological surveillance as a vulnerable group. Interventions need to address
      issues on both sides of the border, other vulnerable groups, and refugees. Strong
      political will and cross border collaboration is mandatory for such
      interventions.

PMID- 18341697
TI  - Effects of cyclic nucleotides on midgut infections and maturation of T. b. brucei
      in G. m. morsitans.
AB  - Cyclic nucleotide signalling through cyclic adenosine monophosphate (cAMP) is
      thought to play an important role in the transformation of the long slender
      (dividing) form to the short-stumpy (arrested) form in the mammalian bloodstream
      but the role of cyclic nucleotides in the tsetse-based part of the trypanosome
      life cycle is unknown. In a series of in vivo experiments, it was found that
      cyclic guanosine monophosphate (cGMP) but not cAMP could induce significantly
      higher rates of midgut infection in tsetse. Continuous feeding of either cGMP or
      cAMP to tsetse had no effect on rates of maturation of established midgut
      infections suggesting that these two parts of the life cycle in tsetse are not
      linked.

PMID- 18341698
TI  - Hepatic abscess in a pre-existed simple hepatic cyst as a late complication of
      sigmoid colon ruptured diverticula: a case report.
AB  - INTRODUCTION: Hepatic abscesses have been reported as a rare complication of
      diverticulitis of the bowel. This complication is recognized more commonly at the
      time of the diagnosis of diverticulitis, or ruptured diverticula, but also can be
      diagnosed prior to surgery, or postoperatively. CASE PRESENTATION: This report
      describes a man who developed an hepatic abscess within a simple hepatic cyst,
      two months after operation for ruptured diverticula of the sigmoid colon. The
      abscess was drained surgically and the patient made a complete recovery.
      CONCLUSION: The development of an hepatic abscess in a pre-existing hepatic cyst,
      secondary to diverticulitis, is a rare complication. A high degree of clinical
      suspicion is required for immediate diagnosis and treatment.

PMID- 18341699
TI  - Hydrological modeling of geophysical parameters of arboviral and protozoan
      disease vectors in Internally Displaced People camps in Gulu, Uganda.
AB  - BACKGROUND: The aim of this study was to determine if remotely sensed data and
      Digital Elevation Model (DEM) can test relationships between Culex
      quinquefasciatus and Anopheles gambiae s.l. larval habitats and environmental
      parameters within Internally Displaced People (IDP) campgrounds in Gulu, Uganda.
      A total of 65 georeferenced aquatic habitats in various IDP camps were studied to
      compare the larval abundance of Cx. quinquefasciatus and An. gambiae s.l. The
      aquatic habitat dataset were overlaid onto Land Use Land Cover (LULC) maps
      retrieved from Landsat imagery with 150 m x 150 m grid cells stratified by levels
      of drainage. The LULC change was estimated over a period of 14 years. Poisson
      regression analyses and Moran's I statistics were used to model relationships
      between larval abundance and environmental predictors. Individual larval habitat
      data were further evaluated in terms of their covariations with spatial
      autocorrelation by regressing them on candidate spatial filter eigenvectors.
      Multispectral QuickBird imagery classification and DEM-based GIS methods were
      generated to evaluate stream flow direction and accumulation for identification
      of immature Cx. quinquefasciatus and An. gambiae s.l. and abundance. RESULTS: The
      main LULC change in urban Gulu IDP camps was non-urban to urban, which included
      about 71.5 % of the land cover. The regression models indicate that counts of An.
      gambiae s.l. larvae were associated with shade while Cx. quinquefasciatus were
      associated with floating vegetation. Moran's I and the General G statistics for
      mosquito density by species and instars, identified significant clusters of high
      densities of Anopheles; larvae, however, Culex are not consistently clustered. A
      stepwise negative binomial regression decomposed the immature An. gambiae s.l.
      data into empirical orthogonal bases. The data suggest the presence of roughly
      11% to 28 % redundant information in the larval count samples. The DEM suggest a
      positive correlation for Culex (0.24) while for Anopheles there was a negative
      correlation (-0.23) for a local model distance to stream. CONCLUSION: These data
      demonstrate that optical remote sensing; geostatistics and DEMs can be used to
      identify parameters associated with Culex and Anopheles aquatic habitats.

PMID- 18341700
TI  - Invasive micropapillary carcinomas arising 42 years after augmentation
      mammoplasty: a case report and literature review.
AB  - BACKGROUND: There has been no definitive consensus regarding the causal
      relationships between foreign bodies in the breast and carcinogenesis. This
      report describes the first case of invasive micropapillary carcinomas after
      augmentation mammoplasty. Multiple tumors located in immediate contact with the
      siliconomas suggested a causal link between the siliconomas and carcinomas. CASE
      PRESENTATION: This report presents the case of a 64-year-old female who underwent
      liquid silicone injections for augmentation mammoplasty 42 years previously.
      Eight years before admission, siliconomas of the left breast were removed due to
      pain and discomfort. The patient visited the hospital for further treatment of
      newly diagnosed carcinoma of the left breast. Images showed multiple tumors
      located in various areas of the left breast. The pathological findings of the
      left breast showed each tumor to be solitary and not continuous with the others.
      The tumors were diagnosed to be invasive micropapillary carcinomas, and they all
      came into immediate contact with the residual siliconomas. The siliconomas were
      therefore suspected to have played a causative role in the development of the
      breast cancer. CONCLUSION: This rare case of multiple invasive micropapillary
      carcinomas following augmentation mammoplasty provides evidence that siliconomas
      may lead to carcinomas. Although a causal relationship was not established
      unequivocally, we review evidence that suggest silicone gel may cause cell damage
      responsible for carcinoma development.

PMID- 18341701
TI  - Comparing the prevalence of rheumatic diseases in China with the rest of the
      world.
AB  - Geographic or ethnic differences in the occurrence of disease often provide
      insights into causes of disease and possible opportunities for disease
      prevention. Persons in China appear to have a consistently lower prevalence of
      rheumatoid arthritis and fibromyalgia than persons in the United States and
      Europe; reasons for these prevalence differences might include genetic
      differences, differences in environmental exposures or a combination of both.
      With increasing obesity, gout is becoming endemic in China. Finally, symptomatic
      knee osteoarthritis is extremely common in China and constitutes a major public
      health problem there.

PMID- 18341702
TI  - A persistently elevated C-reactive protein level in pneumonia may indicate
      empyema.

PMID- 18341703
TI  - On the nature of thumbs.
AB  - Asymmetric regulation of Hox gene expression pre-dates the appearance of tetrapod
      digits, and was co-opted in the development of 'thumbness'. This asymmetric
      expression correlates with independent morphological evolutionary variation of
      digit 1.

PMID- 18341704
TI  - A Caenorhabditis elegans genetic-interaction map wiggles into view.
AB  - Systematic mapping of genetic-interaction networks will provide an essential
      foundation for understanding complex genetic disorders, mechanisms of genetic
      buffering and principles of robustness and evolvability. A recent study of
      signaling pathways in Caenorhabditis elegans lays the next row of bricks in this
      foundation.

PMID- 18341706
TI  - The quest for optimal positive end-expiratory pressure continues.

PMID- 18341705
TI  - Bench-to-bedside review: Mitochondrial injury, oxidative stress and apoptosis-
      there is nothing more practical than a good theory.
AB  - Apoptosis contributes to cell death in common intensive care unit disorders such
      as traumatic brain injury and sepsis. Recent evidence suggests that this form of
      cell death is both clinically relevant and a potential therapeutic target in
      critical illness. Mitochondrial reactive oxygen species (ROS) have become a
      target for drug discovery in recent years since their production is
      characteristic of early stages of apoptosis. Among many antioxidant agents,
      stable nitroxide radicals targeted to mitochondria have attracted attention due
      to their ability to combine electron and free radical scavenging action with
      recycling capacities. Specific mechanisms of enhanced ROS generation in
      mitochondria and their translation into apoptotic signals are not well
      understood. This review focuses on several contemporary aspects of oxidative
      stress-mediated mitochondrial injury, particularly as they relate to oxidation of
      lipids and their specific signaling roles in apoptosis and phagocytosis of
      apoptotic cells.

PMID- 18341707
TI  - How much insulin is acceptable following aneurysmal subarachnoid hemorrhage?

PMID- 18341708
TI  - Innate recognition of non-self nucleic acids.
AB  - The immune system has evolved a plethora of innate receptors that detect
      microbial DNA and RNA, including Toll-like receptors in the endosomal compartment
      and RIG-I-like receptors and Nod-like receptors in the cytosol. Here we discuss
      the recognition of and responses to non-self nucleic acids via these receptors as
      well as their involvement in autoimmune diseases.

PMID- 18341709
TI  - Restoring normoglycaemia: not so harmless.
AB  - Three independent studies of tight glucose control were recently stopped
      prematurely due to an excess mortality in the intensive treatment arm. This
      commentary briefly discusses the potential mechanisms and reminds the potential
      benefits of physiological stress hyperglycemia.

PMID- 18341710
TI  - The Amborella genome: an evolutionary reference for plant biology.
AB  - The nuclear genome sequence of Amborella trichopoda, the sister species to all
      other extant angiosperms, will be an exceptional resource for plant genomics.

PMID- 18341711
TI  - Rheumatologists, take heart! We may be doing something right.
AB  - In the present issue of Arthritis Research & Therapy data are presented
      suggesting that antirheumatic therapies decrease the risk of cardiovascular
      disease in patients with rheumatoid arthritis. The QUEST-RA group, a large
      international collaboration, analyzed data on 4,363 patients in a cross-sectional
      manner. Traditional risk factors were all significantly associated with
      cardiovascular events, and the presence of extraarticular disease significantly
      increased the risk, confirming a previous publication. The most interesting
      analysis in this study suggests that effective antirheumatic treatment, with
      traditional disease-modifying antirheumatic drugs (DMARDs), glucocorticoids, or
      anti-TNF biologics, reduces the risk of cardiovascular disease in rheumatoid
      arthritis. Some methodological issues are discussed, however, and confirmatory
      studies are suggested.

PMID- 18341712
TI  - Rethinking bystander CPR for out-of-hospital cardiac arrest.

PMID- 18341713
TI  - Breast Cancer Research--the first ten years.

PMID- 18341714
TI  - Refractory neuropathic mixed incontinence.

PMID- 18341715
TI  - Prognostic relevance of the histological subtype of renal cell carcinoma.
AB  - OBJECTIVE: According to several studies, when the histological subtype of renal
      cell carcinoma is established it is possible to attribute a different life
      expectancy to each patient. We analyzed the prognostic significance of the
      histological subtype in renal cell carcinoma. MATERIALS AND METHODS: The authors
      retrospectively analyzed the follow-up of 230 patients after radical or
      conservative renal surgery. The histological characteristics of the different
      subtypes of tumor were obtained and the disease-free and cancer-specific survival
      curves for the clear cell, cromophobic, papillary, collecting duct (Bellini)
      subtypes and those with sarcomatoid differentiation were individualized. RESULTS:
      The disease-free and cancer-specific survival rates for clear cell tumors were
      76.6% and 68.0% respectively, 71.2% and 82.1% respectively for the cromophobic
      type, 71.1% and 79.8% respectively for the papillary type, 26.9% and 39.3%
      respectively for the sarcomatoid type, and 0.0% and 0.0% respectively for the
      collecting ducts (p < 0.001). CONCLUSION: The histological subtypes of renal
      tumors can stratify patients into different prognostic groups only when the
      sarcomatoid differentiation is present.

PMID- 18341716
TI  - Retrospective study comparing six- and twelve-core prostate biopsy in detection
      of prostate cancer.
AB  - OBJECTIVE: We compared the safety and efficacy of the 12-core biopsy with those
      of the conventional systematic 6-core biopsy with PSA levels between 4.1 and 20.0
      ng/mL. MATERIALS AND METHODS: This study included 428 patients who underwent a 6
      core biopsy and 128 patients who underwent a 12-core biopsy. Biopsies were
      performed transrectally under ultrasound guidance. The 12-core biopsy scheme
      involved obtaining 6 far lateral cores. RESULTS: For patients with PSA level
      between 4.1 and 10.1 ng/mL, 47 of the 265 patients who underwent 6-core biopsy
      and 32 of the 91 patients who underwent a12-core biopsy were diagnosed with
      prostate cancer (p = 0.0006). Among the patients with a PSA level between 10.1
      and 20.0 ng/mL, 48 of 163 patients who underwent the 6-core biopsy and 16 of 37
      patients who underwent the 12-core biopsy were diagnosed with prostate cancer (p
      = 0.0606). Three of the 95 patients who were diagnosed with prostate cancer
      through the 6-core biopsy and 12 of the 48 patients who were diagnosed through
      the 12-core biopsy had cancer located in the anterior apex. The 12-core biopsy
      increased the diagnostic rate in the apex (p = 0.001). No statistically
      significant differences were found in incidence of complications. CONCLUSION: We
      concluded that the 12-core biopsy is a safe and more effective procedure for
      increasing the diagnostic rate of prostate cancer than the 6-core biopsy in
      patients with PSA level between 4.1 and 10.0 ng/mL, and the most useful
      anatomical area to be added was found to be cores from the anterior apex.

PMID- 18341717
TI  - Evaluation of core and surface body temperatures, prevalence, onset, duration and
      severity of hot flashes in men after bilateral orchidectomy for prostate cancer.
AB  - OBJECTIVE: To assess the prevalence, onset, duration and severity of hot flashes
      in men after bilateral orchidectomy (BO) for prostate cancer, to evaluate body
      temperature changes during hot flashes and to determine whether an elevated
      temperature within a few days after BO can be caused by deprivation of androgen.
      MATERIALS AND METHODS: Patients (n = 101) were questioned about the
      characteristics of their hot flashes after BO for prostate cancer. A subgroup of
      these men (n = 17) were instructed to record their oral and forehead temperatures
      during and at fixed intervals between hot flashes daily for 4 weeks. RESULTS: The
      mean age was 71.6 years, mean follow-up after BO was 33.2 months. Hot flashes
      were reported by 87 men (86%) with previous spontaneous remission in 9 (10%). The
      median time between BO and the onset of hot flashes was 21 days (range 1-730),
      median number of hot flashes 3 per day (range 1-20), and median duration was 120
      seconds (range 5 to 1800). There was no significant difference between median
      oral (36.4(o) C) and forehead (36.0(o) C) temperature in the normal state, but
      during hot flashes the median forehead temperature (37.0(o) C) was higher than
      the oral temperature (36.5(o) C) (p = 0.0004). Both median oral and forehead
      temperatures were higher during hot flashes (36.5(o) C and 37.0(o) C) than in the
      normal state (36.4(o) C and 36.0(o) C, respectively) (p < 0.0001). During hot
      flashes, the oral temperature was 38(o) C to 40(o) C in only 3.2% of 593 readings
      in 17 patients. CONCLUSIONS: The median oral and forehead temperatures are higher
      during hot flashes than in normal periods. Oral temperature elevation > 38(o) C
      within days after a BO is unlikely to be the result of androgen deprivation
      alone.

PMID- 18341718
TI  - Gleason score as predictor of clinicopathologic findings and biochemical (PSA)
      progression following radical prostatectomy.
AB  - OBJECTIVE: There is evidence showing that Gleason grading of prostatic
      adenocarcinoma is one of the most powerful predictors of biological behavior and
      one of the most influential factors used to determine treatment for prostate
      cancer. The aim of the current study was to compare the Gleason score for needle
      biopsy to the Gleason score for the correspondent surgical specimen, find any
      possible difference in the biochemical (PSA) progression following surgery in
      upgraded cases, correlate Gleason score in the specimens to several
      clinicopathologic variables, and compare outcomes between patients with low-grade
      vs. high-grade Gleason and Gleason scores 3+4 vs. 4+3. MATERIALS AND METHODS: The
      study population consisted of 200 consecutive patients submitted to radical
      prostatectomy. Biochemical progression was defined as PSA > or = 0.2 ng/mL. Time
      to PSA progression was studied using the Kaplan-Meier product-limit analysis.
      RESULTS: In 47.1% of the cases, there was an exact correlation and 40.6% of cases
      were underestimated in the biopsies. Half of the tumors graded Gleason 6 at
      biopsy were Gleason score 7 at surgery. These upgraded tumors had outcomes
      similar to tumors with Gleason score 7 in both biopsy and surgery. There was a
      positive correlation of high-grade Gleason score in the surgical specimens to
      higher preoperative PSA, more extensive tumors, positive margins and more
      advanced pathologic staging. Tumors with a Gleason score > or = 7 have lower PSA
      progression-free survival vs. Gleason scores < 7. In this series, there was no
      significant difference when comparing Gleason scores of 3+4 vs. 4+3. CONCLUSIONS:
      The findings support the importance of Gleason grading for nomograms, which are
      used by clinicians to counsel individual patients and help them make important
      decisions regarding their disease.

PMID- 18341719
TI  - Semen and urine culture in the diagnosis of chronic bacterial prostatitis.
AB  - OBJECTIVE: To assess the diagnostic accuracy of semen and urine culture in the
      diagnosis of chronic bacterial prostatitis (CBP). MATERIALS AND METHODS: In 70
      consecutive men suspected of having chronic bacterial prostatitis along with 17
      asymptomatic controls, we obtained urine and semen cultures followed 1 week later
      by the Meares and Stamey test, our reference standard. The interpretation of each
      of the cultures was blind to the results of other tests. RESULTS: 139 men were
      referred for evaluation of chronic bacterial prostatitis and 70 received all
      tests. Additionally, 17 control men volunteered to participate. The Meares and
      Stamey Test was positive in 69 (79%) patients. The semen culture had a
      sensitivity of 45% and a specificity of 94%. The likelihood ratio associated with
      a positive semen culture was 8.1 (95% confidence interval (CI) 1.2 to 55.3); the
      likelihood ratio associated with a negative semen culture was 0.6 (95% CI 0.5 to
      0.7). The urine culture had a sensitivity of 4% and a specificity of 100%. The
      likelihood ratio of a positive urine culture was infinity and of a negative urine
      culture was 0.96 (95% CI 0.9 to 1). CONCLUSIONS: While a positive semen culture
      in a symptomatic patient may suffice to select and start antibiotic treatment
      against chronic bacterial prostatitis, a negative culture does not rule out the
      condition. Urine cultures alone are not useful for diagnosing CBP. The Meares and
      Stamey test remains important for the diagnosis of CBP in practice.

PMID- 18341720
TI  - Prostate specific antigen levels following transurethral resection of the
      prostate.
AB  - OBJECTIVE: Determine how serum prostate-specific antigen (t-PSA) levels and free
      PSA (f/t PSA) ratio change following transurethral resection of the prostate
      (TURP). MATERIALS AND METHODS: Thirty men with a mean age of 67.0 +/- 4.2 years
      (range 46 to 84 years) underwent TURP for BPH between May 2005 and October 2005.
      Preoperative assessment included symptom evaluation with the International
      Prostate Symptom Score (I-PSS) and the prostate volume estimation by transrectal
      ultrasound. Total PSA and f/t PSA ratio were assessed before the procedure, as
      well as 30, 60 and 180 days after the TURP. RESULTS: Clinical improvement after
      TURP, reflected by I-PSS score, was demonstrated as early as 30 days and remained
      stable until the end of the follow-up. Mean t-PSA declined 71% after TURP and 60
      days after surgery the reduction reached its peak, stabilizing afterwards. It
      varied from 6.19 +/- 7.06 ng/mL before surgery to 1.75 +/- 1.66 ng/mL on day 60
      (p < 0.001). The mean baseline f/t PSA ratio was 18.2% +/- 3.4% and was not
      significantly changed at any given time point in the postoperative period (p =
      0.91). There were also no statistically significant differences in t-PSA or f/t
      PSA between patients with and without prostatitis at any time point (p = 0.23).
      Resected prostate fragments weighed 29.9 +/- 19.6 g, corresponding to 39.1% of
      the estimated preoperative prostate volume. Each gram of tissue resected
      decreased PSA by 0.15 +/- 0.11 ng/mL, while 1% prostate volume resected led to a
      reduction of 2.4% +/- 0.4% in serum PSA from baseline. CONCLUSIONS: PSA decreases
      drastically in patients who undergo TURP. These low levels stabilize within 60
      days after surgery. The f/t PSA ratio did not change, and the finding of chronic
      prostatitis did not affect the levels of these variables.

PMID- 18341721
TI  - Sperm defect severity rather than sperm Source is associated with lower
      fertilization rates after intracytoplasmic sperm injection.
AB  - OBJECTIVE: To evaluate the impact of sperm defect severity and the type of
      azoospermia on the outcomes of intracytoplasmic sperm injection (ICSI). MATERIALS
      AND METHODS: This study included 313 ICSI cycles that were divided into two major
      groups according to the source of spermatozoa used for ICSI: 1) Ejaculated (group
      1; n = 220) and 2) Testicular/Epididymal (group 2; n = 93). Group 1 was
      subdivided into four subgroups according to the results of the semen analysis: 1)
      single defect (oligo-[O] or astheno-[A] or teratozoospermia-[T], n = 41), 2)
      double defect (a combination of two single defects, n = 45), 3) triple defect
      (OAT, n = 48), and 4) control (no sperm defects; n = 86). Group 2 was subdivided
      according to the type of azoospermia: 1) obstructive (OA: n = 39) and 2) non
      obstructive (NOA: n = 54). Fertilization (2PN), cleavage, embryo quality,
      clinical pregnancy and miscarriage rates were statistically compared using one
      way ANOVA and Chi-square analyses. RESULTS: Significantly lower fertilization
      rates were obtained when either ejaculated sperm with triple defect or testicular
      sperm from NOA patients (63.4 +/- 25.9% and 52.2 +/- 29.3%, respectively) were
      used for ICSI as compared to other groups ( approximately 73%; P < 0.05).
      Epididymal and testicular spermatozoa from OA patients fertilized as well as
      normal or mild/moderate deficient ejaculated sperm. Cleavage, embryo quality,
      pregnancy and miscarriage rates did not differ statistically between ejaculated
      and obstructive azoospermia groups. However, fertilization, cleavage and
      pregnancy rates were significantly lower for NOA patients. CONCLUSION: Lower
      fertilization rates are achieved when ICSI is performed with sperm from men with
      oligoasthenoteratozoospermic and non-obstructive azoospermic, and embryo
      development and pregnancy rates are significantly lower when testicular
      spermatozoa from NOA men are used.

PMID- 18341722
TI  - Relevance of herniography for accurate diagnosis of patent processus vaginalis in
      cryptorchidism.
AB  - OBJECTIVE: To clarify the role of peritoneography in assessing the patency of
      processus vaginalis (PV) in pediatric patients diagnosed with cryptorchidism.
      MATERIALS AND METHODS: We designed a prospective clinical trial to evaluate the
      patency of PV in boys presenting cryptorchidism. Herniography was performed in
      310 prepubertal boys. Data about the morphology of PV was compared with operative
      findings in those surgically treated patients. Retractile and ectopic testes were
      excluded from the study. RESULTS: Of the 376 undescended testes (310 patients),
      281 cases were associated with an obliterated PV. Herniography revealed 95 cases
      of open PV in cryptorchid boys. The 244 normally descended testes had associated
      patent processus vaginalis in only 31 cases. CONCLUSIONS: Herniography is the
      most relevant procedure for accurate diagnosis of persistent PV. The persistence
      of PV was significantly more frequent when the position of the testes is more
      cranial. The incidence of an open PV decreases with age.

PMID- 18341723
TI  - An effective day case treatment combination for refractory neuropathic mixed
      incontinence.
AB  - OBJECTIVE: Women with drug refractory neurogenic mixed incontinence (NMI) have
      limited minimally invasive treatment options and require reconstructive surgery.
      We examined efficacy of a combination of day case intradetrusor (ID) botulinum
      toxin (BTX-A) bladder injections and transobturator (TOT) or tension free vaginal
      tape (TVT). MATERIALS AND METHODS: Eleven women who are pharmacotherapy
      intolerant or who have drug refractory NMI were treated. Two opted for open
      surgery and the remaining 9 received 1000 units of Dysport diluted in 30 mL
      saline cystoscopically at 30 ID sites followed by TOT in 6 or TVT in 3 as a day
      case combination treatment. Patient demographics, pre and post treatment
      videocystometrogram (VCMG), pad test and International Committee on Incontinence
      Questionnaire (ICIQ) scores were recorded. At 6 weeks (repeat ICIQ, pad test and
      patient satisfaction), at 3 and 12 months (VCMG) and 'current' (ICIQ and patient
      satisfaction) was recorded. RESULTS: The mean age was 56.7 years (range 41 to 78)
      with a mean follow up of 19.1 months (range 7 to 33). All women were continent at
      3 and 12 months. Quality of life (ICIQ scores) improved at 6 weeks (p > 0.001)
      and remained stable up to the last follow up (p > 0.001). Eight women have
      stopped using pads. At 3 months, there was significant improvement in MDP (p >
      0.014) and MCC (p = 0.002). Anticholinergics were discontinued in 7 with global
      high satisfaction with the treatment BTX-A injections were repeated in 4 (mean
      13.5 months). CONCLUSION: Anticholinergic refractory women with NMI can be
      effectively treated as a day case with combination of ID BTX-A injections and TVT
      or TOT.

PMID- 18341724
TI  - Preoperative Valsalva leak point pressure may not predict outcome of mid-urethral
      slings. Analysis from a randomized controlled trial of retropubic versus
      transobturator mid-urethral slings.
AB  - OBJECTIVE: To test the hypothesis that preoperative Valsalva leak point pressure
      (VLPP) predicts long-term outcome of mid-urethra slings for female stress urinary
      incontinence (SUI). MATERIALS AND METHODS: One hundred and forty-five patients
      with SUI were prospectively randomized to two mid-urethra sling treatments:
      Tension free vaginal tape (TVT) or transobturator tape (TOT). They were followed
      up at 3, 6, 12 months post-operatively and then annually for the primary outcome
      variable, i.e. dry or wet and secondary outcome variables such as scores on the
      urogenital distress inventory (UDI-6) and the impact of incontinence on quality
      of life (IIQ-7) questionnaire as well as patient satisfaction as scored on a
      visual analogue scale (VAS). Preoperative VLPP was correlated with primary and
      secondary outcome variables. RESULTS: Mean follow-ups were 32 +/- 12 months
      (range 12-55) for TVT and 31 +/- 15 months (range 12-61) for TOT. When patients
      were analyzed according to VLPP stratification, 95 (65.5%) patients showed a VLPP
      > 60 cm H2O and 50 (34.5%) patients had a VLPP < or = 60 cm H2O. The overall
      objective cure rates were 75.8% for patients with VLPP > 60 cm H2O and 72% for
      those with VLPP < or = 60 cm H2O (p < 0.619). No significant differences in
      objective cure rates emerged when patients were stratified for pre-operative VLPP
      and matched for TOT or TVT procedures: VLPP > 60 cm H2O (82% vs. 68.9% p <
      0.172); VLPP < or = 60 cm H2O (68% vs. 76% p < 0.528). CONCLUSIONS: When patients
      were stratified for preoperative VLPP (< or = or > of 60 cm H2O), preoperative
      VLPP was not linked to outcome after TVT or TOT procedures.

PMID- 18341725
TI  - Posterior repair with perforated porcine dermal graft.
AB  - OBJECTIVE: To compare postoperative vaginal incision separation and healing in
      patients undergoing posterior repair with perforated porcine dermal grafts with
      those that received grafts without perforations. Secondarily, the tensile
      properties of the perforated and non-perforated grafts were measured and
      compared. MATERIALS AND METHODS: This was a non-randomized retrospective cohort
      analysis of women with stage II or greater rectoceles who underwent posterior
      repair with perforated and non-perforated porcine dermal grafts (Pelvicol(TM) CR
      Bard Covington, GA USA). The incidence of postoperative vaginal incision
      separation (dehiscence) was compared. A secondary analysis to assess graft
      tensile strength, suture pull out strength, and flexibility after perforation was
      performed using standard test method TM 0133 and ASTM bending and resistance
      protocols. RESULTS: Seventeen percent of patients (21/127) who received grafts
      without perforations developed vaginal incision dehiscence compared to 7% (5/71)
      of patients who received perforated grafts (p = 0.078). Four patients with
      vaginal incision dehiscence with non-perforated grafts required surgical revision
      to facilitate healing. Neither tensile strength or suture pull out strength were
      significantly different between perforated and non-perforated grafts (p = 0.81, p
      = 0.29, respectively). There was no difference in the flexibility of the two
      grafts (p = 0.20). CONCLUSION: Perforated porcine dermal grafts retain their
      tensile properties and are associated with fewer vaginal incision dehiscences.

PMID- 18341727
TI  - Re: results from three municipal hospitals regarding radical cystectomy on
      elderly patients.

PMID- 18341726
TI  - Effects of repeated extracorporeal shock wave on kidney apoptosis of normal and
      diabetic rat.
AB  - OBJECTIVE: To assess the effect of repeated extracorporeal shock waves (ESW) on
      the apoptosis of renal parenchyma in normal and diabetic rats by the caspase-3
      expression. MATERIALS AND METHODS: 80 rats were assigned for ESW (Direx Tripter
      X1(R) - 14 KVA) to one of three groups with 50% rats with diabetes (A) and 50%
      normal (B) in each: G1 (n = 40): no ESW; G2 (n = 20): one ESW; G3 (n = 20): two
      ESWin an interval of 14 days. The animals were sacrificed 3 days after the ESW
      and samples of the renal parenchyma were histologically prepared, stained by the
      caspase-3 cleavage immunohistochemical method, and the apoptotic index (ApIn) was
      calculated by computer program Image Pro-Plus V 4,5,1 Media Cybernetics ( ApIn =
      number of apoptotic cells in the microscopic section / total cells in the
      microscopic section). RESULTS: There was no statistical difference in ApIn of
      normal rats with one ESW (8.4 +/- 0.2) or two ESW (9.1 +/- 0.3) and both were
      similar to the control group with no ESW (7.9 +/- 0.2). The ApIn of diabetic rats
      with one ESW (7.4 +/- 0.3) was similar to the normal rats with one or two ESW. On
      the other hand, the ApIn was statistically higher in diabetic rats with two ESW
      (11.9 +/- 0.4) than in diabetic rats with one ESW (7.4 +/- 0.3). CONCLUSIONS: The
      ApIn of normal rats with a single (2,000 SW) or repeated ESW (4,000 SW) was
      similar to the control animals without any ESW. In diabetic rats, the repeated
      ESW (4,000 SW) may result in an additional risk of tissue damage expressed by the
      higher ApIn.

PMID- 18341728
TI  - Re: pudendal somatosensory evoked potentials in normal women.

PMID- 18341749
TI  - Are elderly suicide rates improved by increased provision of mental health
      service resources? A cross-national study.
AB  - BACKGROUND: Elderly suicide rates may be influenced by mental health service
      provision. METHODS: A cross-national study examining the hypothesis that the
      relationship between elderly suicide rates and markers of mental health service
      provision would be curvilinear (inverted-U shaped curve) and fit the quadratic
      equation y = a + bx - cx2 (where y is the elderly suicide rate, x is a marker for
      mental health service provision, and a, b and c are constants) was undertaken by
      utilizing data from the World Health Organization. RESULTS: The relationship
      between the logarithm of suicide rates in both sexes in both the elderly age
      bands and the percentage of the total health budget spent on mental health, the
      total number of psychiatric beds per 10,000 population and the total number of
      psychiatrists per 10,000 population were curvilinear (inverted U-shaped curve)
      and fitted the quadratic equation y = a + bx - cx2 with statistical significance.
      CONCLUSIONS: The direction of the causal relationship could be examined in
      longitudinal studies, after further improvement in levels of mental health
      service provision, in individual countries segregated by low and high levels of
      existing mental health service provision.

PMID- 18341750
TI  - Trauma and post-traumatic stress symptoms in former German child soldiers of
      World War II.
AB  - BACKGROUND: The aim of the study was to determine the amount of trauma impact and
      significant post-traumatic stress symptoms, which can indicate a possible post
      traumatic stress disorder (PTSD), in a sample of former German child soldiers of
      World War II. METHODS: 103 participants were recruited through the press, then
      administered a modified Post-traumatic Diagnostic Scale (PDS). RESULTS: Subjects
      reported a high degree of trauma exposure, with 4.9% reporting significant post
      traumatic stress symptoms after WW II, and 1.9% reporting that these symptoms
      persist to the present. CONCLUSION: In line with other studies on child soldiers
      in actual conflict settings, our data document a high degree of trauma exposure
      during war. Surprisingly, the prevalence of significant post-traumatic stress
      symptoms indicating a possible PTSD was low compared to other groups of aging,
      long-term survivors of war trauma. Despite some limitations our data highlight
      the need for further studies to identify resilience and coping factors in
      traumatized child soldiers.

PMID- 18341751
TI  - Discriminatory behavior of family physicians toward a person with Alzheimer's
      disease.
AB  - BACKGROUND: It has been anecdotally suggested that health care professionals have
      stigmatic beliefs about persons with Alzheimer's disease (AD). However, the
      nature and prevalence of those beliefs have yet to be elucidated. The aim of the
      present study is to examine stigma towards a person with AD among primary care
      physicians. METHODS: A nationally representative sample of 501 family physicians
      (54.1% female, mean age = 49, mean years in the profession = 21) were interviewed
      using a computer-assisted telephone interview and a structured questionnaire
      based on an expanded version of attribution theory. RESULTS: The findings showed
      that physicians' discriminatory behavior was especially high in the dimension of
      avoidance and coercion, but low in the dimension of segregation. Two central
      emotions (anger-fear and pity) were found to affect participants' tendency to
      discriminate, as were attributions of dangerousness. CONCLUSIONS: Addressing
      these factors may require targeted education of health professionals as well as
      the enforcement of anti-discrimination policies.

PMID- 18341752
TI  - Depression among newly admitted Australian nursing home residents.
AB  - BACKGROUND: This research concerns the prevalence and course of depression in
      newly admitted nursing home residents. We attempted to recruit consecutive
      admissions into the study, irrespective of cognitive status, enabling a
      comparison of the prevalence and course of depression experienced by cognitively
      intact residents and those exhibiting all levels of cognitive impairment. METHOD:
      Depression was assessed at one month, three months and six months post-admission.
      The assessment of mood in this study entailed the conduct of a semi-structured
      clinical interview, which encompassed DSM-IV criteria and Cornell Scale for
      Depression in Dementia (CSDD) items. RESULTS: Recruitment difficulties resulted
      in a sample of 51 newly admitted residents, drawn from six nursing homes located
      in Victoria, Australia. Of particular interest, throughout the duration of the
      study, only the cognitively impaired were diagnosed with major depression (MD).
      One month post-admission, 24% of the sample were diagnosed with MD, and a further
      20% evidenced a non-major depressive disorder. At the second and third
      assessments, MD was observed in 14% and 15% of residents, respectively. For
      residents who completed all three assessments, there was no appreciable change in
      the proportion diagnosed with a depressive disorder, nor was there a change in
      the levels of depressive symptomatology. CONCLUSION: Although subject to
      limitations, the current study indicated that clinical depression in nursing home
      facilities most often occurs in residents who also exhibit pronounced cognitive
      impairment. These depressions are unlikely to remit spontaneously. Accordingly,
      care staff and general practitioners must be trained in the identification of
      depression in dementia, and any interventions implemented in these facilities
      should be tailored to meet the unique needs of this group.

PMID- 18341753
TI  - Discontinuation of donepezil for the treatment of Alzheimer's disease in
      geriatric practice.
AB  - BACKGROUND: Maintaining continuous pharmacological treatment of patients with
      dementia is often difficult. In the current study we surveyed the discontinuation
      of donepezil, a cholinesterase inhibitor, for the treatment of Alzheimer's
      disease in a Japanese geriatric outpatient clinic in a university hospital.
      METHODS: Using a retrospective chart review from 1 July 2003 to 30 June 2005,
      prescriptions of donepezil and the reasons for discontinuing the prescription in
      a university hospital were determined. The severity of dementia was evaluated by
      the clinical dementia rating (CDR). RESULTS: Out of 264 patients, 140 (53.1%)
      discontinued taking donepezil during the two-year observation period. The mean
      age of the continued group and the discontinued group did not differ
      significantly (79.5 +/- 6.7, 79.8 +/- 6.4, respectively). Kaplan-Meier analysis
      showed that the patients with more severe cognitive impairment (CDR score = 3)
      discontinued donepezil earlier and more frequently. The reasons for
      discontinuation were a change in the doctors treating the patients (n = 71),
      ineffectiveness (n = 16), gastrointestinal side-effects (n = 11), and others (n =
      41). In patients with CDR = 1 or 2, changes of doctors were the most frequent
      reason for discontinuation. However, in patients with CDR = 3, ineffectiveness of
      the medication was the major reason for discontinuation. CONCLUSION: Donepezil
      was frequently discontinued, and the rate of discontinuation was higher in
      patients with advanced dementia.

PMID- 18341754
TI  - Long-chain n-3 polyunsaturated fatty acid from fish oil modulates aortic nitric
      oxide and tocopherol status in the rat.
AB  - In spite of their high oxidisability, long-chain n-3 PUFA protect against CVD.
      Dietary fatty acids modulate the fatty acid composition of lipoproteins involved
      in atherosclerosis. We thought that if long-chain n-3 PUFA were able to increase
      NO production by the aorta, then by its antioxidant activity the NO will prevent
      lipid peroxidation. However, the beneficial effect of NO in vivo on VLDL + LDL
      oxidation would only be possible if NO could diffuse to their lipidic core. Rats
      were fed maize oil- or fish oil as menhaden oil- (MO) rich diets for 8 weeks, to
      study the effects of MOon aortic NO production, NO diffusion into VLDL + LDL, the
      extent of oxidation in native VLDL + LDL and their oxidisability ex vivo. Aortic
      NO production and its alpha-tocopherol content were increased and n-3 PUFA were
      incorporated into the VLDL + LDL. In spite of the higher peroxidisability and the
      low alpha-tocopherol in native VLDL + LDL from rats fed MO, native VLDL + LDL
      from the two groups shared similar electrophoretic patterns, conjugated dienes,
      thiobarbituric acid-reactive substances, total antioxidant capacity, and NO
      diffusibility on VLDL + LDL, indicative of an in vivo protection against
      oxidation. However, these results do not correlate with the ex vivo oxidisability
      of VLDL+ LDL, as NO is lacking. Thus, the in vivo beneficial effects can be
      explained by increased a-tocopherol in aorta and by a compensatory effect of NO
      onVLDL + LDL against the low alpha-tocopherol levels, which may contribute to the
      anti-atherogenic properties of fish oil.

PMID- 18341755
TI  - Urinary felinine excretion in intact male cats is increased by dietary cystine.
AB  - Felinine is a branched-chain sulfur amino acid present in the urine of certain
      Felidae, including domestic cats. The objective of the present study was to
      determine if additional cystine and/or dietary N would increase felinine and N
      acetylfelinine excretion by intact male cats fed a low-protein(LP) diet. Feeding
      five adult intact male cats an LP diet (18.8% of metabolisable energy (ME) as
      protein) v. a high-protein diet (38.6% of ME as protein) resulted in a trend
      (P=0.08) for decreased urinary felinine and no change in N-acetylfelinine
      excretion. In a 23 d study, when the LP diet was supplemented with L-cystine at
      9.3 g/kg DM, urinary felinine:creatinine ratio showed a linear two-fold (121 %)
      increase (P<0.01) from 0.24 (SEM 0.05) to 0.53 (SEM 0.13) after 10 d. Subsequent
      feeding of the LP diet resulted in a decrease in felinine excretion to base
      levels. Plasma gamma-glutamyl felinylglycine concentrations were consistent with
      the excretion of felinine. Supplementation of the LP diet with L-cystine (9.3
      g/kg DM),dispensable amino acids and arginine to a second group (n 5) also
      resulted in a significant (P<0.01) but smaller (+72 %) increase in the daily
      felinine:creatinine ratio (0.25 (SEM 0.04) to 0.43 (SEM 0.05)). The degree of
      felinine N-acetylation within groups was unaffected by dietary addition and
      withdrawal of amino acids. The results indicate that felinine synthesis is
      regulated by cystine availability, and that arginine may be physiologically
      important in decreasing felinine biosynthesis in intact male cats.

PMID- 18341756
TI  - Immunomodulatory effects of the intake of fermented milk with Lactobacillus casei
      DN114001 in lactating mothers and their children.
AB  - The healthy action of probiotics is not only due to their nutritional properties
      and their influence on the gastrointestinal environment, but also to their action
      on the immune system. The aim of the present study was to determine if 6 weeks of
      probiotic intake would be able to modulate the immune system in women who had
      recently delivered and were breast-feeding. The design consisted of a randomised,
      controlled and double-blind nutritional intervention study with parallel groups
      with a sample size of 104 women. The main variable is the T helper type 1/T
      helper type 2 (Th1/Th2) profile determined by measuring interferon-gamma (Th1)
      and IL-4 (Th2) values in peripheral blood by flow cytometry. The modifications of
      cytokines were evaluated in maternal milk by cytometric bead array in a flow
      cytometer and ELISA at three stages of breast-feeding: colostrum, early milk (10
      d) and mature milk (45 d). Additionally, the anthropometry and infectious and
      allergic episodes in the newborn were followed up throughout the first 6 months
      of life. After the consumption of milk fermented with Lactobacillus casei during
      the puerperium, we observed a nonsignificant increase in T and B lymphocytes and
      a significant increase in natural killer cells. A decrease in the pro
      inflammatory cytokine TNF-alpha in maternal milk and fewer gastrointestinal
      disturbances were also observed in the breast-fed child of the mothers who
      consumed L. casei. The intake of milk fermented with L. casei during the
      lactation period modestly contributes to the modulation of the mother's
      immunological response after delivery and decreases the incidence of
      gastrointestinal episodes in the breast-fed child.

PMID- 18341757
TI  - Comparison of body fat estimation using waist:height ratio using different
      'waist' measurements in Australian adults.
AB  - The objective of the present study was to determine differences in predicting
      total and regional adiposity using the waist:height ratio (WHtR) calculated using
      different 'waist' measurements. Body composition of ninety-five males and 121
      female Australian adults (aged 20 years and above) was measured using dual-energy
      X-ray absorptiometry. The WHtR was calculated using: (1) the narrowest point
      between the lower costal border and the top of the iliac crest (WHtR-W), and (2)
      at the level of the umbilicus (WHtR-A). Relationships between calculated WHtR and
      measured body composition, such as percentage body fat (%BF) and percentage trunk
      fat (%TF) were determined. Values obtained from WHtR-A were significantly greater
      than WHtR-W in both groups (P < 0.05). While no correlation differences between
      WHtR-W and WHtR-A in relation to body composition variables were observed,
      females showed significantly lower correlation with lean mass compared with BMI.
      Regression analyses showed that neither WHtR had an age influence on %TF
      estimation. Estimated %BF and %TF were comparable for both WHtR and also with
      estimated values using a BMI of 25 kg/m2. Sensitivity of excess %BF and %TF
      increased by using WHtR-A, particularly in females. In conclusion, the umbilicus
      measurement may be better than using the narrowest site in the WHtR calculation,
      particularly in females. To improve the screening ability of the WHtR and make
      comparisons between studies easier there may be a need to standardise the
      measurement location. Further studies are recommended to confirm the findings
      across different ethnic groups.

PMID- 18341758
TI  - Folate and vitamin B12 status in relation to cognitive impairment and anaemia in
      the setting of voluntary fortification in the UK.
AB  - Concerns about risks for older people with vitamin B12 deficiency have delayed
      the introduction of mandatory folic acid fortification in the UK. We examined the
      risks of anaemia and cognitive impairment in older people with low B12 and high
      folate status in the setting of voluntary fortification in the UK. Data were
      obtained from two cross-sectional studies (n 2403) conducted in Oxford city and
      Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of
      cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45
      pmol/l) with or without high folate status (defined either as serum folate >30
      nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and
      study. Mean serum folate levels increased from 15.8 (sd 14.7) nmol/l in 1995 to
      31.1 (sd 26.2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in
      9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment
      with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR
      1.50 (95 % CI 0.91, 2.46) v. 1.45 (95 % CI 1.19, 1.76)), respectively. The
      associations of cognitive impairment with low B12 status were also similar using
      the higher cut-off point of 60 nmol/l for folate status ((OR 2.46; 95 % CI 0.90,
      6.71) v. (1.56; 95 % CI 1.30, 1.88)). There was no evidence of modification by
      high folate status of the associations of low B12 with anaemia or cognitive
      impairment in the setting of voluntary fortification, but periodic surveys are
      needed to monitor fortification.

PMID- 18341759
TI  - How reliable and robust are current biomarkers for copper status?--comments by
      Brewer and Althaus.

PMID- 18341760
TI  - Modelling the resource implications and budget impact of new reimbursement
      guidelines for the management of cow milk allergy in Finland.
AB  - OBJECTIVE: To assess the impact of the decision by Kela (The Social Insurance
      Institution) to adopt guidelines for the management of food allergies in
      children, developed by the Finnish Medical Society Duodecim, as the basis for
      reimbursing clinical nutrition preparations for the treatment of cow milk allergy
      (CMA) in Finland. METHODS: A decision model was constructed using published
      clinical outcomes and clinician-derived resource utilisation estimates. The model
      was used to estimate the net resource implications and associated costs of Kela's
      new policy for the annual cohort of 1443 new CMA sufferers over the first 6
      months following referral to a specialist. The analysis was conducted from the
      perspective of Kela, patients and Finnish society. RESULTS: Kela's new policy for
      reimbursing clinical nutrition preparations for the treatment of CMA is expected
      to increase healthcare resource use, including a 10% increase in the number of
      specialist visits over the first 6 months following referral. Consequently,
      Kela's 6-monthly expenditure on 1443 new CMA sufferers following referral is
      expected to increase by 12% from 889,389 euros to 992,761 euros. Additionally,
      parents' costs are expected to increase by 10% and fathers' absenteeism from work
      to increase by 11% within the first 6 months following referral. CONCLUSION: It
      is important to validate guidelines in clinical practice before their
      implementation. Within the limitations of our model, Kela's new criteria for
      reimbursing clinical nutrition preparations for the treatment of CMA is expected
      to increase healthcare resource use in paediatric departments in public hospitals
      in Finland and increase costs to Kela, patients and Finnish society.

PMID- 18341761
TI  - Transfer of T cells from intranasal ovalbumin-immunized mice ameliorates allergic
      response in ova-sensitized recipient mice.
AB  - Mucosal immunotherapy is suggested as a treatment strategy for tolerance
      induction in allergic diseases. The purpose of this study was to determine the
      effect of transferred splenic T cells from intranasal ovalbumin (OVA)-immunized
      mice to naive mice before sensitization on its impact of cytokine production and
      airway histopathology. BALB/c mice in group I received intranasal immunotherapy
      (days1-6), carboxylfluorescein succinyl ester (CFSE)-labeled splenocytes or
      splenic T cells were i.v. transferred to naive recipients (group II) before OVA
      sensitization. Acute murine asthma model was established by two i.p. OVA
      injections (days 21 and 28) and seven OVA nebulizations (days 42-48) in groups I,
      II and III. Groups III and IV served as asthma model and control, respectively.
      CFSE-labeled cells in splenocytes and lymph node lymphocytes, lung
      histopathology, IL-4, IL-10, and interferon (IFN) gamma cytokines of recipients
      were analyzed 24 hours after OVA nebulization challenge. CFSE-labeled T cells
      from group I were detected in spleen and regional lymph nodes of the OVA
      sensitized recipients (group II). Smooth muscle and thickness of airways were
      less in intranasal OVA immunotherapy and OVA-sensitized recipients when compared
      with the asthma model (p < 0.05). Area of inflammation was significantly
      suppressed in OVA-sensitized recipients compared with the asthma model (p <
      0.01). IL-10 and IFN-gamma levels in splenocyte supernatants were significantly
      increased in intranasal immunotherapy and OVA-sensitized recipients compared with
      asthma model and controls (p < 0.01). IL-4 levels were significantly less in
      intranasal immunotherapy group and the OVA-sensitized recipient group when
      compared with asthma the model group (p < 0.05). This study suggests that
      intranasal immunotherapy with allergens regulates T-cell responses and
      ameliorates airway histopathology in sensitized mice, hence, encouraging mucosal
      tolerance induction as a suitable treatment of allergic diseases.

PMID- 18341762
TI  - The effect of bipolar I disorder and major depressive disorder on workforce
      function.
AB  - This investigation was undertaken to explore and compare the effect of bipolar I
      disorder (BD) and major depressive disorder (MDD) on workforce function. The data
      for this analysis were procured from the Canadian Community Health Survey (CCHS
      1.2). The sample consisted of 20,747 individuals (>or=18 years or older and
      currently working); the proportions screening positive for lifetime BD and MDD
      were 2.4% and 11.2%, respectively. Individuals with BD or MDD had a significantly
      lower mean annual income, compared to people without these disorders. Individuals
      with BD had a significantly lower annual income when compared to MDD (p < 0.05).
      Results from a multiple logistic regression also indicate that employed
      individuals with BD had greater odds of reporting one or more mental health
      disability days in the past two weeks, compared with those with MDD (OR = 1.6;
      95% CI = 1.0 to 2.6). Currently employed individuals with BD had lower odds of
      "good job security" relative to those with MDD (OR = 0.6 95% CI = 0.5 to 0.9).
      The data herein underscore the pernicious effect of BD on workforce function, and
      suggest that opportunistic screening for BD in all individuals utilizing
      employment assistance programs for depression might be warranted.

PMID- 18341763
TI  - A new population-based measure of the economic burden of mental illness in
      Canada.
AB  - This paper presents a comprehensive measure of the incremental economic burden of
      mental illness in Canada which incorporates the use of medical resources and
      productivity losses due to long-term and short-term disability, as well as
      reductions in health-related quality of life (HRQOL), for the diagnosed and
      undiagnosed population with mental illness. The analysis was based on the
      population-based Canadian Community Health Survey Cycle 2.1 (2003). For all
      persons, we measured all health services utilization, longterm and short-term
      work loss, and health-related quality of life and their dollar valuations, with
      the economic burden being the difference in dollar measures between the
      populations with and without mental health problems. In total, the economic
      burden was $51 billion in 2003. Over one-half was due to reductions in HRQOL. The
      current accepted practice in economic assessments is to include changes in
      medical resource use, work loss, and reductions in HRQOL.

PMID- 18341764
TI  - The evolution of HPV-related anogenital cancers reported in Quebec - incidence
      rates and survival probabilities.
AB  - Non-cervical anogenital cancers (i.e. anal, vulvar, vaginal and penile cancers)
      associated with the human papillomavirus (HPV), for which HPV is known to be the
      necessary cause of carcinogenesis, are poorly documented due to their relatively
      low incidence rate. The aim of this study is to describe the incidence rates of
      these cancers between 1984 and 2001, and their relative survival probabilities,
      in Quebec (Canada) between 1984 and 1998. The incidence of these cancers is on
      the rise, particularly anal cancer in women and, more recently (since 1993-95),
      vulvar cancer. Between 1984-86 and 1993-95, the 5-year relative survival
      probability for men with anal cancer decreased from 57% to 46%, while that for
      penile cancer dropped from 75% to 59%. However, during the same period, the 5
      year relative survival probability for women with anal cancer rose from 56% to
      65%, and remained stable for cervical and vulvar cancers, at 74% and 82%,
      respectively.

PMID- 18341765
TI  - A new brief measure of oral quality of life.
AB  - INTRODUCTION: We developed a brief measure of the impact of oral conditions on
      individual functioning and well-being, known as oral quality of life. METHODS:
      Among older male veterans (N = 827) and community dental patients (N = 113), we
      administered surveys consisting of extant oral quality of life items, using
      clinical dental data from the veteran samples. We assigned each oral quality of
      life item to a theoretical dimension, conducted an iterative series of multitrait
      scaling analyses to examine the item-fit with the dimensions, reduced the number
      of items, and examined the psychometric characteristics of new scales and their
      association with clinical indices. RESULTS: We developed two brief oral quality
      of life scales, one consisting of 12 items and the other of 6, the latter a
      subset of the former. Each demonstrated sound psychometric properties and was
      sensitive to clinical indices. CONCLUSION: The two brief oral quality of life
      scales can be used to assess the population-based impact of oral conditions as
      well as outcomes of dental care.

PMID- 18341767
TI  - Addressing heart disease and stroke prevention through comprehensive population
      level approaches.

PMID- 18341768
TI  - Heart-healthy and stroke-free, 2008.

PMID- 18341769
TI  - Perspectives from the Cardiovascular Health Council.

PMID- 18341770
TI  - Applying the findings of public health research to communities: balancing ideal
      conditions with real-world circumstances.

PMID- 18341771
TI  - Trends in fruit and vegetable consumption among U.S. men and women, 1994-2005.
AB  - INTRODUCTION: Eating a diet high in fruits and vegetables as part of an overall
      healthful diet can help lower chronic disease risk and aid in weight management.
      Increasing the percentage of Americans who consume enough fruits and vegetables
      every day is part of the Healthy People 2010 objectives for the nation. Assessing
      trends in consumption of these foods is important for tracking public health
      initiatives to meet this goal and for planning future objectives. METHODS: We
      assessed total and sex-specific changes in daily consumption of fruits and
      vegetables among 1,227,969 adults in the 50 U.S. states and the District of
      Columbia who participated in the Behavioral Risk Factor Surveillance System from
      1994 through 2005. To estimate changes in consumption according to dietary
      recommendations that were in place during the years examined, we used geometric
      mean and the percentage of people eating fruits or vegetables or both five or
      more times per day. Estimates were standardized for sex, age, and race/ethnicity
      and analyzed by multivariate regression. RESULTS: From 1994 through 2005, the
      geometric mean frequency of consumption of fruits and vegetables declined
      slightly (standardized change: men and women, -0.22 times/day; men, -0.26
      times/day; women, -0.17 times/day). The proportion of men and women eating fruits
      or vegetables or both five or more times per day was virtually unchanged (men,
      20.6% vs 20.3%; women, 28.4% vs 29.6%); however, we found small increases for men
      aged 18 to 24 years and for women who were aged 25 to 34 years, non-Hispanic
      black, or nonsmokers. Consumption of fruit juice and non-fried potatoes declined
      for both sexes. CONCLUSION: The frequency of fruit and vegetable consumption
      changed little from 1994 through 2005. If consumption is to be increased, we must
      identify and disseminate promising individual and environmental strategies,
      including policy change.

PMID- 18341772
TI  - Cultural attitudes toward weight, diet, and physical activity among overweight
      African American girls.
AB  - INTRODUCTION: The growing epidemic of childhood obesity has led to an increasing
      focus on strategies for prevention. However, little is known about attitudes and
      perceptions toward weight, diet, and physical activity among American youth, and
      particularly among young African American females. This pilot study sought to
      qualitatively explore cultural attitudes and perceptions toward body image, food,
      and physical activity among a sample of overweight African American girls.
      METHODS: We recruited 12 overweight girls, aged 12 to 18 years, from a hospital
      based pediatric diabetes screening and prevention program. Five semistructured
      group interviews were conducted to explore attitudes on weight, diet, and
      physical activity. Sessions averaged 1 hour and were conducted by trained
      interviewers. Data were transcribed and evaluated for content and relevant
      themes. RESULTS: The following themes emerged: weight and body size preferences
      were primarily determined by the individual and her immediate social circle and
      were less influenced by opinions of those outside of the social circle; food
      choices depended on texture, taste, appearance, and context more than on
      nutritional value; engagement in recreational physical activity was influenced by
      time constraints from school and extracurricular activities and by neighborhood
      safety; participation in structured exercise was limited because of the cost and
      time related to maintenance of personal aesthetics (hair and nails); and
      celebrities were not perceived as role models for diet and physical activity
      habits. CONCLUSION: In this sample of girls, the findings imply that perceptions
      of weight and healthy lifestyle behaviors are largely determined by environmental
      and personal influences. These factors should be considered in the development of
      healthy-weight interventions for African American girls.

PMID- 18341773
TI  - Worksite characteristics and environmental and policy supports for cardiovascular
      disease prevention in New York state.
AB  - INTRODUCTION: Worksite policy and environmental supports that promote physical
      activity, healthy eating, stress management, and preventive health screenings can
      contribute to the prevention of cardiovascular disease and lower employer costs.
      This study examines the availability of these four categories of supports in a
      statewide survey of New York State worksites. METHODS: In 2002, we recruited a
      statewide sample of worksites in New York State with 75 or more employees to
      participate in a mailed survey assessing worksite policy and environmental
      supports for wellness and health promotion. The overall response rate was 34.8%.
      The analysis included data from 832 worksites. RESULTS: Worksite size was an
      independent predictor of health promotion supports with small (75-99 employees)
      and medium-small (100-199 employees) worksites reporting significantly fewer
      policy and environmental supports in all four categories than worksites with 300
      or more employees. Worksites in which most employees were nonwhite reported fewer
      supports for physical activity, healthy eating, and stress management than
      worksites in which most employees were white. A wellness committee or wellness
      coordinator was associated with more health promotion supports, regardless of the
      size of the worksite or composition of its workforce. CONCLUSION: Worksites with
      fewer than 200 employees have an increased need for assistance in establishing
      environmental and policy supports promoting cardiovascular health. Worksites that
      have a wellness committee or coordinator are better able to establish and sustain
      supports with the potential to improve the health of their workers.

PMID- 18341774
TI  - Start-up of the colorectal cancer screening demonstration program.
AB  - INTRODUCTION: In 2005, the Centers for Disease Control and Prevention funded five
      sites to implement the Colorectal Cancer Screening Demonstration Program
      (CRCSDP). An evaluation is being conducted that includes a multiple case study.
      Case study results for the start-up period, the time between initial funding and
      screening initiation, provide details about the program models and start-up
      process and reveal important lessons learned. METHODS: The multiple case study
      includes all five CRCSDP sites, each representing a unique case. Data were
      collected from August 2005 through September 2006 from documents, observations,
      and more than 70 interviews with program staff and stakeholders. RESULTS: Sites
      differed by geographic service area, screening modality selected, and service
      delivery structure. Program models were influenced by two factors: preexisting
      infrastructure and the need to adapt programs to fit local service delivery
      structures. Several sites modeled program components after their National Breast
      and Cervical Cancer Early Detection Program. Medical advisory boards convened by
      all sites provided clinical support for developing program policies and quality
      assurance plans. Partnerships with comprehensive cancer control programs
      facilitated access to financial and in-kind resources. CONCLUSION: The program
      models developed by the CRCSDP sites offer a range of prototypes. Case study
      results suggest benefits in employing a multidisciplinary staff team, assembling
      a medical advisory board, collaborating with local partners, using preexisting
      resources, designing programs that are easily incorporated into existing service
      delivery systems, and planning for adequate start-up time.

PMID- 18341775
TI  - Facilitators and challenges to start-up of the colorectal cancer screening
      demonstration program.
AB  - INTRODUCTION: The Centers for Disease Control and Prevention (CDC) funded the
      Colorectal Cancer Screening Demonstration Program in 2005. To assess the
      feasibility of providing community-based colorectal cancer screening, CDC is
      conducting a multiple-case study as part of a larger evaluation effort. This
      article highlights key facilitators and challenges common to the five programs
      studied during the start-up period. METHODS: The multiple-case study that
      includes all five program sites is being conducted during the 3-year program as
      part of process evaluation efforts. Data collection for program start-up occurred
      during August 2005 through September 2006. Data include approximately 70
      interviews with program staff and stakeholders, document review, and
      observations. Both case-specific and cross-case analyses were conducted. RESULTS:
      On the basis of the cross-case analysis, we identified four factors that
      facilitated program start-up and four factors that challenged program start-up.
      Facilitating factors included 1) pre-existing program infrastructure, 2)
      partnerships, 3) clinical expertise, and 4) program champions. Factors
      challenging program start-up included 1) contracts with endoscopists, 2)
      resources for treating medical complications of screening and for cancer
      treatment, 3) administrative barriers, and 4) resource limitations. Additionally,
      preplanning was critical, allowing programs to efficiently initiate activities
      once funds became available. CONCLUSION: The most important facilitator
      identified was the ability to build on pre-existing infrastructure, which
      provided experienced staff, partnerships, and provider relationships, as well as
      aided program integration with other chronic disease programs. Results also
      suggest that substantial planning and partnership development can begin before
      funds are secured to implement a colorectal cancer screening program.

PMID- 18341776
TI  - A comparative case study on active transport to and from school.
AB  - INTRODUCTION: This study investigates active-transport-to-school initiatives
      through the Active Living by Design Community Action Model framework. The
      framework outlines five strategies that influence physical activity: preparation,
      promotion, programs, policies, and physical projects. METHODS: A comparative case
      study was conducted to investigate active-transport-to-school initiatives at two
      North Carolina schools. A group of key stakeholders from each site was
      interviewed (N = 16), including principals, physical education teachers, public
      safety officers, city planners, regional transportation planners, city council
      members, and parent representatives. Content analysis was carried out using NVivo
      software, and data were evaluated using the framework. RESULTS: Applications
      designed around all five strategies positively influenced active-transport-to
      school programs. Both schools used similar strategies including promotional
      tactics, policies, and physical projects; however, only one used all five
      strategies. The scope and duration of these strategies varied by school and
      ultimately seemed to influence their success. Enablers and challenges to active
      transport-to-school programs were identified, including funding, school location,
      available infrastructure, community involvement, school support, parental buy-in,
      and sufficient program promotion. CONCLUSION: The quality of the strategies, not
      their mere presence or use, proved important in active-transport-to-school
      programs. These results suggest that a multidisciplinary approach that develops
      promotional materials, resources, school support, and environmental changes to
      sustain factors that influence parental buy-in will prove critical to the success
      of future walk-to-school initiatives.

PMID- 18341777
TI  - Awareness of necessity to call 9-1-1 for stroke symptoms, upstate New York.
AB  - INTRODUCTION: Stroke is the third leading cause of death and a leading cause of
      disability in New York State. A New York study determined that only 19.9% of
      patients arrived at a designated stroke center within 3 hours of symptom onset.
      Yet, receiving treatment within 90 minutes of stroke symptom onset is optimal for
      improved outcomes. Delay in recognition of stroke symptoms and their severity
      contributes to treatment delay. METHODS: A random-digit-dialed, list-assisted
      telephone survey about stroke knowledge was administered to 1789 adults aged 30
      years or older in upstate New York in 2006. Bivariate and regression analysis
      were used to examine factors associated with intent to call 9-1-1 for symptoms of
      stroke. RESULTS: The largest proportion of respondents (72.4%; 95% confidence
      interval [CI], 69.9%-74.8%) reported they would call 9-1-1 if they noticed they
      or someone else had difficulty speaking, and the fewest (33.3%; 95% CI, 30.7%
      36.0%) respondents reported they would call 9-1-1 for trouble seeing or double
      vision. Multivariate analysis found that those who had a history of delay in
      getting medical care in the past 6 months had decreased odds of intending to call
      9-1-1 for stroke symptoms (difficulty speaking: adjusted odds ratio [AOR], 0.76;
      95% CI, 0.58-1.00; trouble seeing: AOR, 0.69; 95% CI, 0.53-0.91; facial droop:
      AOR, 0.85; 95% CI, 0.65-1.11; arm weakness: AOR, 0.80; 95% CI, 0.63-1.03). Age,
      education, and history of a stroke or heart event were not consistently
      associated with intent to call 9-1-1. CONCLUSION: Survey respondents do not
      interpret some stroke symptoms as urgent enough to activate the emergency medical
      system. History of delaying care is a behavioral pattern that influenced intent
      to call 9-1-1.

PMID- 18341778
TI  - Process evaluation of the Los Angeles Unified School District Nutrition Network.
AB  - INTRODUCTION: This study evaluated the Los Angeles Unified School District
      Nutrition Network, a large multicomponent nutrition and physical activity program
      in an ethnically diverse school district, launched in 2000. METHODS: We
      calculated descriptive statistics and performed hierarchical logistic regression
      on school-level demographic and implementation data. RESULTS: Thirty-six percent
      of eligible schools participated in 2001, and 79% of participating schools
      reapplied the following year. Elementary schools and schools that applied for
      grant money were more likely to re-apply. Produce sampling was the most
      frequently cited program highlight, and making purchases with program grant money
      was the most frequently cited challenge. CONCLUSION: Our findings suggest that
      schools serving students of low socioeconomic status and diverse ethnicities can
      be recruited into a large program to promote healthy dietary choices and physical
      activity, especially elementary schools. Effectiveness and institutionalization
      of the program might be positively affected by fostering local ownership,
      allowing school personnel who apply for the grant to tailor the program to their
      individual schools.

PMID- 18341779
TI  - Validity of the SF-12 for use in a low-income African American community-based
      research initiative (REACH 2010).
AB  - INTRODUCTION: The objective of our study was to assess the psychometric
      properties of the Medical Outcomes Study's 12-Item Short Form Survey Instrument
      (SF-12) for use in a low-income African American community. The SF-12, a commonly
      used functional health status assessment, was developed based on responses of an
      ethnically homogeneous sample of whites. Our assessment addressed the
      appropriateness of the instrument for establishing baseline indicators for mental
      and physical health status as part of Nashville, Tennessee's, Racial and Ethnic
      Approaches to Community Health (REACH) 2010 initiative, a community-based
      participatory research study. METHODS: A cross-sectional random residential
      sample of 1721 African Americans responded to a telephone survey that included
      the SF-12 survey items and other indicators of mental and physical health status.
      The SF-12 was assessed by examining item-level characteristics, estimates of
      scale reliability (internal consistency), and construct validity. RESULTS:
      Construct validity assessed by the method of extreme groups determined that SF-12
      summary scores varied for individuals who differed in self-reported medical
      conditions. Convergent and discriminate validity assessed by multitrait analysis
      yielded satisfactory coefficients. Concurrent validity was also shown to be
      satisfactory, assessed by correlating SF-12 summary scores with independent
      measures of physical and mental health status. CONCLUSION: The SF-12 appears to
      be a valid measure for assessing health status of low-income African Americans.

PMID- 18341780
TI  - Implementing case management in New York State's partnerships for publicly funded
      breast cancer screening.
AB  - INTRODUCTION: This research aimed to explore differences in the implementation of
      case management among local breast cancer screening partnerships in New York
      State after changes in federal public policy in 1998 and to achieve a better
      understanding of case management in a new and distinct practice setting. Capacity
      and willingness to implement change were theorized to explain local differences
      in implementation. Local breast cancer screening programs that received federal
      funding through the New York State Department of Health were invited to
      participate in the study. METHODS: A mail survey was administered to the
      directors of New York's 53 local breast cancer screening partnerships in 2003.
      The survey included questions about willingness and capacity to implement case
      management and a scale to assess case management program philosophy. Factor
      analysis and correlations were used to compare willingness and capacity with
      differences in implementation. RESULTS: Two common factors--task focus and self
      identity focus--were identified as factors that differentiated case management
      programs. Task-focus partnerships undertook a broader range of tasks but were
      less likely to report autonomy in making program changes. Self-identity
      partnerships were less likely to report difficulties with other agencies and
      scored highly on innovation, involvement in work, and interest in client service.
      Having a nurse as the case manager, being aware of the standards of case
      management, and providing health education were associated with both task focus
      and self-identity focus. CONCLUSION: The study identified distinct styles of
      implementation. These styles have implications for the breadth of services
      provided, such as whether client-level services only are offered. Interagency
      coordination was facilitated in partnerships with comprehensive case management.

PMID- 18341781
TI  - Correlation of obesity with elevated blood pressure among racial/ethnic minority
      children in two Los Angeles middle schools.
AB  - INTRODUCTION: To identify anthropometric and fitness correlates of elevated blood
      pressure, serum cholesterol, and glycated hemoglobin, we examined anthropometric
      and physiologic biomarkers among racial/ethnic minority children aged 11 to 13
      years in two urban Los Angeles middle schools. We explored the potential for
      using obesity or fitness level as screening variables for cardiovascular disease
      risk factors in these students. METHODS: During regularly scheduled physical
      education classes, we collected data on demographic characteristics, height,
      weight, blood pressure, nonfasting total serum cholesterol, glycated hemoglobin,
      time to run/walk 1 mile, and a range of self-reported behaviors. A total of 199
      sixth-graders (121 Latinos, 78 African Americans) participated in the study.
      RESULTS: Bivariate analyses indicated that 48.6% of sixth-graders were of
      desirable weight, 17.5% were overweight, 29.9% were at risk for overweight, and
      4.0% were underweight. Higher weight was associated with higher levels of serum
      cholesterol, systolic blood pressure, and diastolic blood pressure (P values for
      all associations <.02) but not with glycated hemoglobin. Multivariate analyses
      maintained the findings with regard to blood pressure but not serum cholesterol.
      CONCLUSION: Overweight status could be a screening variable for identifying youth
      at risk for high blood pressure. Obesity prevention and intervention programs and
      policies need to target low-income racial/ethnic minority children. Assessment of
      hypertension status also seems warranted in low-income racial/ethnic minority
      sixth-graders, as does early intervention for children at high risk.

PMID- 18341782
TI  - Cost of starting colorectal cancer screening programs: results from five
      federally funded demonstration programs.
AB  - INTRODUCTION: In 2005, the Centers for Disease Control and Prevention (CDC)
      started a 3-year colorectal cancer screening demonstration project and funded
      five programs to explore the feasibility of a colorectal cancer program for the
      underserved U.S. population. CDC is evaluating the five programs to estimate
      implementation cost, identify best practices, and determine the most cost
      effective approach. The objectives are to calculate start-up costs and estimate
      funding requirements for widespread implementation of colorectal cancer screening
      programs. METHODS: An instrument was developed to collect data on resource use
      and related costs. Costs were estimated for start-up activities, including
      program management, database development, creation of partnerships, public
      education and outreach, quality assurance and professional development, and
      patient support. Monetary value of in-kind contributions to start-up programs was
      also estimated. RESULTS: Start-up time ranged from 9 to 11 months for the five
      programs; costs ranged from $60,602 to $337,715. CDC funding and in-kind
      contributions were key resources for the program start-up activities. The budget
      category with the largest expenditure was labor, which on average accounted for
      67% of start-up costs. The largest cost categories by activities were management
      (28%), database development (17%), administrative (17%), and quality assurance
      (12%). Other significant expenditures included public education and outreach (9%)
      and patient support (8%). CONCLUSION: To our knowledge, no previous reports
      detail the costs to begin a colorectal cancer screening program for the
      underserved population. Start-up costs were significant, an important
      consideration in planning and budgeting. In-kind contributions were also critical
      in overall program funding. Start-up costs varied by the infrastructure available
      and the unique design of programs. These findings can inform development of
      organized colorectal cancer programs.

PMID- 18341783
TI  - Obesity and diabetes in New York City, 2002 and 2004.
AB  - INTRODUCTION: Obesity and diabetes have increased rapidly nationwide, yet
      reliable information on these disease trends in local urban settings is
      unavailable. We undertook this study to characterize trends in obesity and
      diagnosed diabetes from 2002 to 2004 among white, black, and Hispanic adult
      residents of New York City. METHODS: We used data from the Community Health
      Survey, an annual random-digit-dial telephone survey of approximately 10,000 New
      York City adults aged 18 years or older, and from the Behavioral Risk Factor
      Surveillance System, a similar nationwide survey. Main outcome measures were body
      mass index (BMI), calculated from self-reported height and weight, and self
      reported diabetes. RESULTS: In 2 years, the prevalence of obesity increased 17%
      in New York City, from 19.5% in 2002 to 22.8% in 2004 (P < .0001). The prevalence
      of diagnosed diabetes also increased 17%, from 8.1% in 2002 to 9.5% in 2004 (P <
      .01). Nationally, the prevalence of obesity increased by 6% during this same time
      period (P < .05), and diabetes prevalence did not increase significantly. The
      median BMI among white adults in New York City was 25.1 kg/m(2), significantly
      lower than among Hispanics (26.4 kg/m(2)) and blacks (26.6 kg/m(2), P < .05). The
      prevalence of diabetes increased across all BMI categories. DISCUSSION: The rapid
      increase in obesity and diabetes in New York City suggests the severity of these
      twin epidemics and the importance of collecting and analyzing local data for
      local programming and policy making.

PMID- 18341784
TI  - Addressing stroke signs and symptoms through public education: the Stroke Heroes
      Act FAST campaign.
AB  - INTRODUCTION: In 2003, only 18% of Massachusetts adults were aware of all signs
      and symptoms of stroke, but 80% would call 9-1-1 if they thought someone was
      having a stroke or heart attack. Because early recognition leads to early
      treatment and improved clinical outcomes, increasing symptom recognition could
      have an impact on stroke survival and stroke patients' quality of life. METHODS:
      We conducted secondary research to identify messages with evidence-based
      effectiveness for communicating stroke signs and symptoms. From these results, a
      Stroke Heroes Act FAST animation was created and concept-tested. Non-Hispanic
      white and non-Hispanic black women aged 40 to 64 years received education on
      stroke signs and symptoms. Knowledge change about stroke signs and symptoms was
      calculated immediately following and 3 months after the education session.
      RESULTS: Using Stroke Heroes Act FAST educational materials that were developed,
      72 women (mean age, 54 years; 15.5% were non-Hispanic blacks) received education
      about signs and symptoms of stroke and took the pretests and posttests to assess
      knowledge change. Immediately after the education session, significant increases
      were seen in the percentage of participants who recognized that facial droop (92%
      vs 99%, P = .02) and arm weakness or numbness (86% vs 97%, P = .004) were
      symptoms of stroke. Of the 65 participants who were given the 3-month follow-up
      survey, 100% remembered slurred speech and facial drooping as symptoms; 98.5%
      recalled arm weakness or numbness; and 97% would call 9-1-1 if they thought
      someone was having a stroke. None of these is a significant change from the
      posttest. CONCLUSION: The Stroke Heroes Act FAST kit may be a useful tool for
      improving knowledge of stroke signs and symptoms among adults.

PMID- 18341785
TI  - Determinants of the use of breast cancer screening among women workers in urban
      Mexico.
AB  - INTRODUCTION: This case-control study aimed to determine critical factors
      influencing the use of clinical breast examination and mammography among women
      workers in Monterrey, Mexico. METHODS: We determined case and control status from
      survey results. Cases were defined in accordance with the guidelines of the
      Official Mexican Standard as lack of at least one clinical breast examination
      during the past year by surveyed women. For women older than 40 years, cases were
      further defined as lack of at least one mammogram in the previous 2 years and,
      for women older than 50, lack of a mammogram in the previous year. Controls were
      defined as adherence by surveyed women to these guidelines. Participants (N = 306
      clerks aged 18-60) provided information about their practices, knowledge, and
      perceptions regarding breast cancer screening. Factors identified by odds ratio
      analysis as significantly different between cases and controls were analyzed by
      multivariate logistic regression. RESULTS: Survey participants' knowledge about
      the utility of breast self-examination (odds ratio, 6.0; 95% confidence interval,
      1.0-33.9), perception that the health care system has enough equipment and
      personnel for clinical breast examination (odds ratio, 4.7; 95% confidence
      interval, 1.7-13.2), and perception that they have enough time to wait for and
      receive clinical breast examinations (odds ratio, 2.5; 95% confidence interval,
      1.1-5.8) significantly predisposed women to use screening services independent of
      years of formal education, number of pregnancies, number of living children,
      hours worked per week, and monthly family income. CONCLUSION: Perception of
      organizational and structural factors played a significant role in screening use.
      Our findings have implications for the general population, provider practices,
      community interventions, and future development of strategies to increase use of
      screening services in similar locales.

PMID- 18341786
TI  - Pilot study of a faith-based physical activity program among sedentary blacks.
AB  - INTRODUCTION: Physical activity participation is low among blacks, and strategies
      are needed to successfully create immediate and sustained behavior change related
      to physical activity. Churches can play an important role in health promotion
      efforts among blacks because of their central role in spiritual guidance,
      communication, social support, and networking. This pilot study evaluated the
      feasibility and acceptability of implementing a physical activity program for
      sedentary black adults in churches. METHODS: We used a
      preintervention/postintervention single-group design to evaluate the effect of a
      3-month faith-based physical activity intervention on daily walking and moderate-
      and vigorous-intensity physical activity among sedentary blacks. Eighty-seven
      black adults participated in eight group sessions that included discussion of
      physical activity-related topics, an instructor-led physical activity session,
      and weekly incentives to promote physical activity. We used a questionnaire to
      assess moderate and vigorous physical activity in minutes per week at baseline
      and after 3 months. Walking was assessed weekly in steps per day by using a
      pedometer. RESULTS: Participants (mean age, 52 yrs; mean body mass index, 35
      kg/m(2)) reported 27 +/- 54 and 10 +/- 25 minutes per week in moderate-intensity
      and vigorous-intensity physical activity, respectively, and walked 4822 +/- 2351
      steps per day at baseline. After 12 weeks, moderate- and vigorous-intensity
      physical activity increased by 67 +/- 78 and 44 +/- 66 minutes per week,
      respectively (P </= .01), and daily walking increased by 1373 +/- 728 steps per
      day (P < .001). CONCLUSION: These data suggest that a faith-based physical
      activity intervention may be an appropriate strategy for increasing physical
      activity among sedentary black adults. Future research will determine the impact
      of this program in a randomized, controlled design.

PMID- 18341787
TI  - Strategies for controlling blood pressure among low-income populations in
      Georgia.
AB  - BACKGROUND: In Georgia an estimated 32% of blacks and 28% of whites have high
      blood pressure. In 2004 the rate of death from stroke in Georgia was 12% higher
      than the national average, and blacks in the state have a 1.4 times greater rate
      of death from stroke than that of whites. CONTEXT: The Georgia legislature funds
      the Stroke and Heart Attack Prevention Program (SHAPP) to provide treatment and
      medications for indigent Georgians. The median rate of blood pressure (BP)
      control among SHAPP enrollees is approximately 60%, compared with the national
      average of 35%. METHODS: SHAPP was evaluated through interviews with key health
      care and administrative staff and through focus groups of patients in two
      clinics. CONSEQUENCES: Outcomes for patients were increased knowledge of their BP
      and improved compliance with taking medication and keeping clinic appointments.
      INTERPRETATION: Successful components of SHAPP include an easy enrollment
      process; affordable medication; use of evidence-based, documented protocols and
      patient tracking systems; routine follow-up of patients; and effective
      communication between staff and patients. Challenges and recommendations for
      improvement are identified.

PMID- 18341788
TI  - A case study of the South Puget Intertribal Planning Agency's comprehensive
      cancer control planning and community mobilization process.
AB  - BACKGROUND: The high rates of cancer among American Indians and Alaska Natives
      are of growing concern. CONTEXT: In response to high cancer rates, national,
      state, and tribal organizations have worked to assess knowledge, attitudes,
      beliefs, and screening practices related to cancer in American Indian and Alaska
      Native communities and to increase awareness and use of cancer screening. The
      National Comprehensive Cancer Control Program (NCCCP) of the Centers for Disease
      Control and Prevention is one such effort. NCCCP's comprehensive cancer control
      (CCC) planning process provides a new approach to planning and implementing
      cancer control programs. The CCC process and components for American Indians and
      Alaska Natives are not yet fully understood because this is a fairly new approach
      for these communities. Therefore, the purpose of our case study was to describe
      the CCC process and its outcomes and successes as applied to these communities
      and to identify key components and lessons learned from the South Puget
      Intertribal Planning Agency's (SPIPA's) CCC planning and community mobilization
      process. METHODS: We used interviews, document reviews, and observations to
      collect data on SPIPA's CCC planning and community mobilization process.
      CONSEQUENCES: We identified the key components of SPIPA's CCC as funding and
      hiring key staff, partnering with outside organizations, developing a project
      management plan and a core planning team, creating community cancer orientations,
      conducting community cancer surveys, developing a community advisory committee,
      ongoing training and engaging of the community advisory committee, and supporting
      the leadership of the communities involved. INTERPRETATION: The CCC planning
      process is a practicable model, even for groups with little experience or few
      resources. The principles identified in this case study can be applied to the
      cancer control planning process for other tribes.

PMID- 18341789
TI  - Emergency medical services data for cardiovascular disease surveillance, program
      planning, and evaluation in Maine.
AB  - Rapid access to medical treatment is a key determinant of outcomes for
      cardiovascular events. Emergency medical services (EMS) play an important role in
      delivering early treatment for acute cardiovascular events. Attention has
      increased on the potential for EMS data to contribute to our understanding of
      prehospital treatment. Maine recently began to explore the possible role of EMS
      data in cardiovascular disease surveillance and cardiovascular health program
      planning and evaluation. We describe the Maine EMS data system, discuss findings
      on ease of data use and data quality, provide a sample of findings, and share how
      we plan to use EMS data for program planning and evaluation of community-level
      interventions and to partner with EMS provider organizations to improve
      treatment. Our objective is to increase understanding of the promise and
      limitations of using EMS data for cardiovascular disease surveillance and program
      planning and evaluation.

PMID- 18341790
TI  - Prehospital and emergency department capacity for acute stroke care in Minnesota.
AB  - INTRODUCTION: Stroke is the third leading cause of death in Minnesota. One
      strategy to reduce the burden of stroke is to implement systems-level
      improvements in the prehospital and acute care settings. Two surveys conducted in
      2006 obtained information about current practices and capacities of emergency
      medical services and emergency departments in Minnesota. METHODS: In 2006, the
      Minnesota Department of Health and the Minnesota Stroke Partnership (the
      statewide stroke collaborative group) conducted two surveys. The survey for
      emergency medical services organizations, mailed to every licensed ambulance
      service in Minnesota, asked about transportation policies and training needs. The
      survey for hospitals, mailed to every hospital in the state, asked about capacity
      to treat acute stroke. Results were calculated using simple frequency analyses.
      RESULTS: Of 257 surveys mailed to ambulance services, 199 (77%) were returned.
      Ambulance services generally considered stroke an emergency. Training on stroke
      was reported most effective in person annually or semiannually. Of 133 surveys
      mailed to hospitals, 120 (90%) were returned. Stroke capacity differed markedly
      between hospitals in rural areas and hospitals in the large Minneapolis-St. Paul
      metropolitan area. Many hospitals, particularly small hospitals, reported lacking
      stroke protocols. Training for stroke is needed overall but particularly in small
      hospitals. CONCLUSION: Transport and treatment of people with acute stroke in
      Minnesota vary by hospital size and location. Standardization of transport and
      protocols for acute treatment may increase efficiency and overall care for stroke
      patients. In addition, the need to train ambulance personnel and emergency
      departments about stroke remains high.

PMID- 18341791
TI  - The WISEWOMAN program: reflection and forecast.
AB  - The WISEWOMAN program targets low-income under- and uninsured women aged 40-64
      years for screening and interventions aimed at reducing the risk of heart
      disease, stroke, and other chronic diseases. The program enters its third phase
      on June 30, 2008. Design issues and results from Phase I and Phase II have been
      published in a series of papers. We summarize remaining challenges, which were
      identified through systematic research and evaluation. Phase III will address
      these challenges through a number of new initiatives such as allowing
      interventions of different intensities, taking advantage of resources for
      promoting community health, and providing evidence-based interventions through
      the program's Center of Excellence. Finally, we provide a framework and vision so
      that organizational, community, and other partners can make the case for the
      importance of the program to their communities and for what is needed to make it
      work.

PMID- 18341792
TI  - A collaborative approach to collecting data on children's oral health and weight
      status, Georgia, 2005.

PMID- 18341793
TI  - Tools for developing, implementing, and evaluating state policy.
AB  - Policy can improve health by initiating changes in physical, economic, and social
      environments. In contrast to interventions focused on individual people, policies
      have the potential to affect health across populations. For this reason, the
      Division for Heart Disease and Stroke Prevention of the Centers for Disease
      Control and Prevention (CDC) advises states funded under the Heart Disease and
      Stroke Prevention Program to engage in activities supporting the development and
      maintenance of policies that can help reduce the burden of cardiovascular
      disease. Currently, the Division for Heart Disease and Stroke Prevention funds
      programs in 33 states and the District of Columbia to promote cardiovascular
      health. One goal of these programs is to build states' capacity to develop,
      implement, track, and sustain population-based interventions that address heart
      disease and stroke. Because of the critical role of policy in these activities,
      CDC provides guidance in developing, implementing, and evaluating policy. In
      2004, the division contracted with Mathematica Policy Research, Inc, to conduct
      the Heart Disease and Stroke Prevention Policy Project, which included
      development of an online database of state heart disease and stroke prevention
      policies and a mapping application to show which states have these policies. We
      discuss the method for developing the database, mapping application, and other
      tools to assist states in developing, implementing, and evaluating heart disease
      and stroke prevention policies. We also highlight lessons learned in developing
      these tools and ways that states can use the tools in their policy and program
      planning.

PMID- 18341794
TI  - A Purchaser's Guide to Clinical Preventive Services: a tool to improve health
      care coverage for prevention.
AB  - INTRODUCTION: In 2005, representatives from the Centers for Disease Control and
      Prevention partnered with the National Business Group on Health and the Agency
      for Healthcare Research and Quality to form a work group for developing A
      Purchaser's Guide to Clinical Preventive Services: Moving Science into Coverage.
      This guide, designed as a tool for employers, describes recommended clinical
      preventive services for 46 conditions. The guide includes the scientific evidence
      and benefits language that employers need to include comprehensive clinical
      preventive services in their medical benefit plans. METHODS: The work group
      determined that the guide would address conditions that 1) affected a large
      percentage of the working population, 2) were costly to control, and 3) had well
      defined and accepted recommendations for preventive services. Subject matter
      experts from the Centers for Disease Control and Prevention, the National
      Business Group on Health, and the Agency for Healthcare Research and Quality
      developed or reviewed statements of scientific evidence for 46 diseases and
      conditions. RESULTS: The Purchaser's Guide, written for an employer audience,
      includes descriptions for recommended clinical preventive services and their cost
      savings, syntheses of supporting evidence, strategies for prioritization, and
      recommendations to improve the delivery and use of preventive services. Twelve
      hundred copies were sent to more than 275 members of the National Business Group
      on Health and other purchasers of health care; training sessions on the Guide
      were held for 228 business leaders, health benefit consultants, and health plan
      administrators; and an online version was created through the Web sites of the
      National Business Group on Health and the Centers for Disease Control and
      Prevention. The online version has received more than 260,000 hits since its
      release. CONCLUSION: In 2007, the National Business Group on Health reported that
      some Fortune 500 companies will be using the Purchaser's Guide when negotiating
      their health benefit contracts and developing their health care strategies.
      Further research is under way to determine whether the Guide influences employers
      to purchase recommended clinical preventive services.

PMID- 18341795
TI  - Adapting logic models over time: the Washington State Heart Disease and Stroke
      Prevention Program experience.
AB  - Logic models are graphic representations of the relationship between program
      activities and their intended effects and are used for both program planning and
      evaluation. Logic models can provide an important foundation for program
      evaluation by identifying evaluation questions that most appropriately assess
      program processes and outcomes and by guiding measurement decisions. We
      demonstrate how logic models can be used to plan program evaluation by describing
      the adoption of logic modeling by the Washington State Heart Disease and Stroke
      Prevention Program (WaHDSPP) and by specifying the changes in process and use of
      logic models since the program's initial funding. Our paper describes how a logic
      model was used in generating the program evaluation plan for the WaHDSPP,
      including the identification of evaluation questions and development of
      indicators to track progress effectively. We describe the use of evaluation
      results, as well as steps state programs can take to use logic models in program
      evaluation.

PMID- 18341796
TI  - NHLBI step-by-step approach to adapting cardiovascular training and education
      curricula for diverse audiences.
AB  - Racial and ethnic minority communities need to be involved in developing health
      information to ensure its cultural appropriateness, improve its acceptability,
      and stimulate adoption of healthy behaviors. The National Heart, Lung, and Blood
      Institute at the National Institutes of Health adapted a heart-health curriculum
      for Latinos into culturally appropriate curricula for American Indians/Alaska
      Natives, African Americans, and Filipinos. Lessons learned from this process can
      assist public health practitioners interested in adapting science-based heart
      health information into practical health education messages that meet the
      cultural and contextual needs of diverse groups.

PMID- 18341797
TI  - The role of public health in promoting quality improvement in care for stroke and
      heart disease.

PMID- 18341798
TI  - Modeling the local dynamics of cardiovascular health: risk factors, context, and
      capacity.

PMID- 18341799
TI  - Development of a federally funded demonstration colorectal cancer screening
      program.
AB  - Colorectal cancer is the second leading cause of cancer-related mortality among
      U.S. adults. In 2004, treatment costs for colorectal cancer were $8.4 billion.
      There is substantial evidence that colorectal cancer incidence and mortality are
      reduced with regular screening. The natural history of this disease is also well
      described: most colorectal cancers develop slowly from preexisting polyps. This
      slow development provides an opportunity to intervene with screening tests, which
      can either prevent colorectal cancer through the removal of polyps or detect it
      at an early stage. However, much less is known about how best to implement an
      effective colorectal cancer screening program. Screening rates are low, and
      uninsured persons, low-income persons, and persons who have not visited a
      physician within a year are least likely to be screened. Although the Centers for
      Disease Control and Prevention (CDC) has 15 years of experience supporting the
      National Breast and Cervical Cancer Early Detection Program for the underserved
      population, a similar national program for colorectal cancer is not in place. To
      explore the feasibility of implementing a national program for the underserved
      U.S. population and to learn which settings and which program models are most
      viable and cost-effective, CDC began a 3-year colorectal cancer screening
      demonstration program in 2005. This article describes briefly this demonstration
      program and the process CDC used to design it and to select program sites. The
      multiple-methods evaluation now under way to assess the program's feasibility and
      describe key outcomes is also detailed. Evaluation results will be used to inform
      future activities related to organized screening for colorectal cancer.

PMID- 18341800
TI  - The topography of poverty.

PMID- 18341802
TI  - Preventing school dropouts should start in preschool.

PMID- 18341805
TI  - [Standardizing the diagnosis and treatment of chronic heart failure following new
      guidelines].

PMID- 18341803
TI  - Parental education key to health for parents and children.

PMID- 18341806
TI  - [Guidelines for the diagnosis and management of chronic heart failure].

PMID- 18341807
TI  - [Efficacy of cardiac resynchronization therapy-defibrillator for treating
      patients with chronic heart disease].
AB  - OBJECTIVE: To observed the clinical efficacy of cardiac resynchronization therapy
      defibrillator (CRT-D) in selected patients with chronic heart failure one year
      after implantation. METHODS: Seventeen patients with drug-refractory heart
      failure received CRT-D implantation (6 patients were implanted with InSync
      Sentry). The underlying heart diseases were dilated cardiomyopathy in 12 patients
      and ischemic heart disease in 5 patients. There were 13 patients with a history
      of ventricular tachycardia/ventricular fibrillation. RESULTS: CRT-D were
      successfully implanted in all patients without complication. The mean left
      ventricular pacing threshold was 1.6 V. The defibrillation threshold was no more
      than 20 J. During a mean follow-up of 13 months, no death occurred and LV
      function was improved. The shock induced by ventricular tachycardia was delivered
      in 5 patients and alarming due to heart failure occurred twice in 1 patient.
      CONCLUSIONS: The implantation of CRT-D for treating refractory heart failure
      patients is feasible and safe. The application of CRT-D was associated with an
      improved cardiac function and a reduced risk of sudden cardiac death.

PMID- 18341808
TI  - [Factors associated with efficacy of cardiac resynchronization therapy for
      patients with congestive heart failure].
AB  - OBJECTIVE: The efficacy of cardiac resynchronization therapy (CRT) in patients
      with congestive heart failure and the potential factors associated with responder
      or nonresponder were investigated. METHODS: Fifty three patients with congestive
      heart failure (42 with sinus rhythm and 11 with atrial fibrillation) underwent
      CRT were enrolled in this study. Conventional echocardiography and tissue Doppler
      imaging were performed in each patient before implantation and 6 month post
      implantation. Clinical response was defined as improvement of one NYHA functional
      class and echocardiographic response was defined as a reduction in LV end
      systolic volume by > 15% or an increase of absolute value of LVEF > 5%. RESULTS:
      The clinical response rate was 75% and echocardiographic response rate was 69.8%
      during 6 month follow-up. The echocardiographic response rate for patients with
      atrial fibrillation was lower than that for patients with sinus rhythm (45.5% vs.
      76.2%, P < 0.05). In patients with sinus rhythm, higher response rate was seen in
      patients with widen QRS duration, lower pulmonary systolic pressure and prolonged
      left ventricular pre-ejection time (LVPT) while response rate was not affected by
      LVEF, left ventricular volume, NYHA functional class and intra-ventricular
      dyssynchrony. CONCLUSIONS: Response rate to CRT was lower in patients with atrial
      fibrillation compared to patients with sinus rhythm. In patients with sinus
      rhythm, QRS duration, LVPT and pulmonary systolic pressure were useful parameters
      to predict the response to CRT.

PMID- 18341809
TI  - [Effect of cardiac resynchronization therapy on cardiac function post A-V and V-V
      optimization].
AB  - OBJECTIVE: To assess the effect of A-V, V-V delay optimization on cardiac
      function and clinical improvement in patients with refractory heart failure
      underwent cardiac resynchronization therapy (CRT). METHOD: Thirty-two patients
      with chronic heart failure received CRT and cardiac function was measured at 7
      days, 3 months and 6 months post CRT before and after A-V and V-V delay
      optimizations. RESULTS: A-V delay optimization was initiated in 28, 10 and 6
      cases at 7th day, 3rd month and 6th month after CRT. V-V delay optimization was
      performed in 29, 6 and 5 cases at 7th day, 3rd month and 6th month after CRT. Ts
      SD, LVEF, VTI and E/Em were significantly improved after CRT compared to pre-CRT
      (P < 0.01, P < 0.05, P < 0.05, P < 0.05; respectively). Compared to pre
      optimization, the indexes of ventricular synchronization were significantly
      improved (P < 0.05) while indexes of cardiac function remained unchanged post
      optimization at 7th day after CRT. The indexes of ventricular synchronization
      post optimization were similar at 7th, 3rd and 6th months after CRT (P > 0.05).
      LVEF and diastolic filling time were significantly increased after 6 months CRT
      post A-V, V-V delay optimization (P < 0.01). CONCLUSION: A-V, V-V delay
      optimization at 7th day after CRT can significantly improve ventricular
      synchronization and is associated with further improved cardiac function 6 months
      after CRT.

PMID- 18341810
TI  - [Right ventricular desynchronization in patients with pacemaker syndrome].
AB  - OBJECTIVE: To observe the incidence of ventricular desynchronization in patients
      with or without pacemaker syndrome (PMS). METHODS: The systolic peak velocity,
      the acceleration and the time to peak velocity of the interventricular septum
      (IVS), left ventricular (LV) and right ventricular (RV) lateral wall were
      detected by tissue Doppler imaging (TDI) in 14 atrial fibrillation patients
      without pacemaker implantation (control), 18 atrial fibrillation patients without
      PMS and 16 atrial fibrillation patients with PMS. All patients were free of valve
      disease, myocardial infarction, severe pulmonary hypertension, low left
      ventricular eject fraction (< or = 50%), significant segmental hypokinesis of
      ventricular wall or complete bundle branch block. RESULTS: Compared to the
      control patients, the systolic peak velocity and the accelerations on lateral
      walls of the LV and RV reduced significantly in patients with implanted
      pacemakers (P < 0.05). The intervals to peak velocity of the IVS and LV lateral
      walls were significantly prolonged [PMS group (80.13 +/- 26.92) ms vs. (25.60 +/-
      4.30) ms, P < 0.01; without PMS group (76.22 +/- 23.32) ms vs. (25.60 +/- 4.30)
      ms, P < 0.01] and the intervals to peak velocity of the IVS and RV lateral walls
      significantly shortened [PMS group (16.33 +/- 6.85) ms vs. (40.70 +/- 7.60) ms, P
      < 0.01; without PMS group (21.20 +/- 7.34) ms vs. (40.70 +/- 7.60) ms, P < 0.01].
      The systolic peak velocities, the accelerations of the IVS and bilateral walls
      and the intervals to peak velocity of the IVS and LV lateral wall were similar in
      patients with and without PMS (P > 0.05), however, the intervals to peak velocity
      of the IVS and RV lateral wall was significant shorter in patients with PMS
      compared to that of patients without PMS [(16.33 +/- 6.85) ms vs. (21.20 +/-
      7.34) ms, P < 0.01]. CONCLUSION: RV desynchronization but not LV
      desynchronization might play an important role in patients with PMS.

PMID- 18341811
TI  - [Effects of rapid atrial pacing on L-type calcium channel subunits and potassium
      channel Kv4.3 expressions in rabbits].
AB  - OBJECTIVE: To investigate rapid atrial pacing (RAP) induced atrial
      ultrastructural changes and mRNA and protein expression changes of L-type calcium
      channel subunits and potassium channel Kv4.3 in a rabbit model. METHODS: Thirty
      six rabbits were electrically paced at a frequency of 600 beats/min for durations
      ranging from 0 - 48 h via bipolar endocardial leads through surgical techniques.
      Ultrastructural changes of the atrium were observed through a transmission
      electron microscope (TEM), L-type calcium channel subunits and potassium channel
      Kv4.3 expressions at mRNA and protein levels were analyzed by reverse
      transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS:
      Atrial ultrastructure changes characterized by mitochondrial vacuolization,
      myofilament lysis, and glycogen accumulation were detected obvious at 3 h post
      pacing. Down-regulated mRNA expression of Ca(2+) channel beta1 and alpha1
      subunits was observed 6 h post pacing, Kv4.3 mRNA down-regulation occurred 24 h
      post pacing, auxiliary subunit alpha2 was not affected by pacing. Protein
      expression of alpha1c subunit and potassium channel Kv4.3 paralleled their mRNA
      expression changes. CONCLUSION: RAP induced ultrastructural changes of the atrium
      and down-regulated mRNA and protein expressions of L-type calcium channel
      subunits and potassium channel Kv4.3 occurred thereafter in response to
      intracellular calcium overload induced by RAP.

PMID- 18341814
TI  - [Gene (SCN5A) mutation analysis of a Chinese family with Brugada syndrome].
AB  - OBJECTIVE: To analyze the gene mutations on the cardiac sodium channel gene SCN5A
      in a Chinese family with Brugada syndrome. METHOD: Polymerase chain reaction and
      DNA sequencing were used to screen gene mutations on the cardiac sodium channel
      gene SCN5A in all family members of a Chinese pedigree with Brugada syndrome,
      single strand conformation polymorphism analysis were performed in 136 normal
      controls to detect the mutations of SCN5A gene. RESULT: Two heterozygosis
      mutations, which include a missense mutation (Y1494N) and a same sense mutation
      (A29A), were identified on SCN5A gene in the proband with Brugada syndrome and
      these mutations were not detected in other family members with Brugada syndrome
      and in controls. CONCLUSION: We detected a reported polymorphism site (A29A) and
      a novel missense mutation (Y1494N) on SCN5A in this Chinese family with Brugada
      syndrome.

PMID- 18341815
TI  - [Efficacy of intravenous aspirin use in patients with acute coronary syndrome].
AB  - OBJECTIVE: To compare the efficacy of intravenous versus oral aspirin use in
      patients with acute coronary syndrome (ACS). METHODS: ACS patients were randomly
      treated with intravenous aspirin (300 mg/d, IA, n = 30), low oral aspirin (100
      mg/d, OA1, n = 32) or high oral aspirin (300 mg/d, OA2, n = 33). Aspirin
      sensitivity was tested by optical platelet aggregation using adenosine
      diphosphate (ADP) and arachidonic acid (AA). The serum CD62p contents were
      examined by Flow cytometry. RESULTS: Platelet aggregation expressed as ratio of
      reduction of ADP and AA post various aspirin were similar among 3 groups [IA: ADP
      (12.0 +/- 10.4)%, AA (6.7 +/- 11.2)%; OA1: ADP (6.0 +/- 14.6)%, AA (6.9 +/-
      12.3)%; OA2: ADP (9.4 +/- 16.6)%, AA (7.3 +/- 13.0)%, all P > 0.05]. CD62p
      decreasing level post various aspirin were also similar among groups [IA: (10.9
      +/- 18.6)%, OA1: (9.0 +/- 11.8)%, OA2: (7.1 +/- 15.7)%, all P > 0.05]. Side
      effects and MACE post various aspirin use were comparable among groups.
      CONCLUSION: Inhibiting efficacy on platelets function by intravenous aspirin (300
      mg/d) was comparable to that of by oral aspirin (100 mg/d, 300 mg/d) in patients
      with acute coronary syndrome and could be used as an alternative route for
      patients who can't take oral aspirin.

PMID- 18341816
TI  - [The study on the tolerability of perindopril in patients with stable coronary
      heart disease].
AB  - OBJECTIVE: To evaluate the tolerability of perindopril dose-adjustment from 4
      mg/d to 8 mg/d in Chinese patients with stable coronary heart disease (CHD).
      METHODS: CHD patients with or without hypertension were eligible to this open
      lebel, multicenter study. Before admission, all patients received and tolerated
      perindopril 4 mg/d for at least 1 month. Adverse events, blood pressure, heart
      rate, Na(+), K(+), Cr, BUN at baseline, week 4 and week 8 were recorded. RESULTS:
      A total of 109 patients with stable CHD were included in this study, 18 out of
      109 (16.5%) patients experienced mild adverse events during observation period.
      No serious adverse event was recorded. Perindopril 8 mg/d was well tolerated in
      102 patients (93.6%). One patient (0.9%) withdrew from the study because of
      severe cough. In patients with elevated baseline blood pressure, switching
      perindopril from 4 mg/d to 8 mg/d significantly lowered blood pressure from
      (149.4 +/- 7.6)/(84.1 +/- 11.0) mm Hg (1 mm Hg = 0.133 kPa) to (128.8 +/-
      14.2)/(79.5 +/- 8.9) mm Hg (P < 0.01). Serum electrolytes, creatinine and BUN
      were stable during study period. CONCLUSION: Perindopril 8 mg/d can be well
      tolerated by Chinese patients with stable coronary heart disease.

PMID- 18341817
TI  - [The incidence of thrombosis after implantation of drug-eluting stents in
      patients with coronary artery disease in the real world: a single center registry
      study].
AB  - OBJECTIVE: To observe the incidence rate of stent thrombosis after implantation
      of drug-eluting stents (DES) in patients with coronary artery disease (CAD) in
      the real world. METHODS: A total of 8190 consecutive CAD patients underwent
      implantation with Cypher or Cypher Select stents (Cordis, USA, n = 2986), TAXUS
      stents (Boston Scientific Corp., USA, n = 1587) and Chinese Rapamycin eluting
      stents (Firebird, Microport Medical Company, China, n = 3617) for enrolled in
      this single center registry study from Dec.2001 to April 2007. One-year follow-up
      was completed in 5412 patients (2210 Cypher or Cypher select stents, 1238 TAXUS
      stents and 1964 Firebird stents). Two-year follow-up was finished in 2176
      patients (1245 Cypher or Cypher Select stents, 558 TAXUS stents and 373 Firebird
      stents). 80.1% of all the lesions were the type B2 and type C lesions. All
      patients were treated with aspirin plus clopidogrel for at least 9 months post
      DES. RESULTS: Among 8190 patients, 17 patients had acute stent thrombosis
      (0.21%): 7 in the Cypher group, 4 in the TAXUS group, 6 in the Firebird group; 23
      patients had subacute stent thrombosis (0.28%): 8 in Cypher group, 6 in TAXUS
      group and 9 in Firebird group. The incidence rate of acute and subacute
      thrombosis was 0.49% (40/8190) and incidence of thrombosis was similar among the
      three groups (0.50% in Cypher group, 0.63% in TAXUS group and 0.41% in Firebird
      group, P > 0.05). One-year follow-up showed that late thrombosis rate was 0.63 %
      (34/5412) and similar among the groups (0.63% in Cypher group, 0.89% in TAXUS
      group and 0.46% in Firebird group, P > 0.05). Two-year follow-up showed that late
      thrombosis rate was 0.74 % (16/2176) and was similar among the 3 groups (0.72% in
      Cypher group, 0.90% in TAXUS group and 0.54% in Firebird group, P > 0.05).
      CONCLUSION: This study indicates that using the first-generation DES to treat
      complex coronary lesions is safe and effective and the incidence of late
      thrombosis remains low (< 1%) under double antiplatelet treatment.

PMID- 18341818
TI  - [The efficacy of percutaneous coronary intervention combined percutaneous
      thrombectomy on coronary thrombotic lesions in patients with acute myocardial
      infarction].
AB  - OBJECTIVE: To evaluate the efficacy of percutaneous coronary intervention (PCI)
      combined percutaneous thrombectomy on coronary thrombotic lesions in patients
      with acute myocardial infarction (AMI). METHODS: PCI were performed in 56
      patients with AMI and positive coronary thrombus shown by angiography and these
      patients were randomly divided into PCI therapy group (n = 28) and PCI combined
      percutaneous thrombectomy group (n = 28). Real-time myocardial contrast
      echocardiography (RT-MCE) was performed at 24h and 1 week after PCI. Contrast
      score index (CSI), regional wall motion score index (WMSI), endocardial length of
      contrast defect (CDL), and wall motion abnormality (WML) were calculated. The
      plasma level of hs-CRP was measured by immunonephelometry. The plasma
      concentration of N-terminal proB-type natriuretic peptide (NT-proBNP) and matrix
      metalloproteinase-9 (MMP-9) were detected by enzyme-linked immunosorbent assay
      (ELISA). RESULTS: CSI, WMSI, CDL and WML at 24 hours and 1 week post procedure as
      well as the levels of hs-CPR and NT-proBNP at 1 week post procedure [(4.56 +/-
      1.98) mg/L vs. (5.96 +/- 2.03) mg/L, P < 0.05; (544.7 +/- 185.3) pmol/L vs.
      (897.6 +/- 215.9) pmol/L, P < 0.01] were significantly lower in PCI combined
      percutaneous thrombectomy group than those in PCI group in various time points.
      There were no differences in the plasma level of MMP-9 between the two groups
      [(672.7 +/- 175.9) microg/L vs. (609.6 +/- 196.5) microg/L, P > 0.05] at 1 week
      after PCI. CONCLUSIONS: PCI combined percutaneous thrombectomy can significantly
      reduce no-reflow phenomenon, improve microcirculation and myocardial dysfunction.
      Thus PCI combined percutaneous thrombectomy is a feasible therapy in patients
      with AMI.

PMID- 18341819
TI  - [Association between positive autoantibodies against AT1-receptor and cardiac
      remodeling in patients with hypertension].
AB  - OBJECTIVE: To observe the association between positive autoantibodies against
      AT(1)-receptor and cardiac remodeling in primary hypertensive patients. METHODS:
      Echocardiography was performed and serum autoantibodies against AT(1)-receptor
      were detected by enzyme linked immunosorbent assay (ELISA) in 592 patients with
      primary hypertension. The differences on blood pressure level, course of
      hypertension, vasoactive substance and echocardiography parameters between the
      positive group and negative group were compared. Factors related to left
      ventricular enlargement were analyzed by multiple logistic regressions. RESULTS:
      The positive percentage of autoantibodies against AT(1)-receptor was 38.0%
      (225/592). End-diastolic right atrial and left ventricular diameters in positive
      group were significantly larger than that in negative group (P = 0.049 and P =
      0.044, respectively). Regression analysis demonstrated that positive
      autoantibodies against AT(1)-receptor, male gender, diastolic blood pressure and
      course of hypertension were related to left ventricular enlargement (all P <
      0.05). CONCLUSION: The autoantibodies against AT(1)-receptor is associated with
      left ventricular and right atrial enlargement in hypertensive patients.

PMID- 18341820
TI  - [Plasma hydrogen sulfide and homocysteine levels in hypertensive patients with
      different blood pressure levels and complications].
AB  - OBJECTIVE: The present study was designed to observe the plasma concentrations of
      hydrogen sulfide (H(2)S) and homocysteine (HCY) in hypertensive patients with
      different blood pressure levels and complications. METHODS: A total of 165
      outpatients with essential hypertension were involved in this study (84 males, 81
      females, mean age 59.81 +/- 10.60 years old). There were 28 new-onset untreated,
      137 ever-treated patients. Among ever-treated patients, blood pressure was normal
      in 38, grade 1 hypertension in 43, grade 2 and 3 hypertension in 56 patients.
      Thirty-two patients were accompanied with coronary heart disease (CAD), and 42
      patients were accompanied with stroke. A total of 32 age- and sex-matched healthy
      controls (18 males) were also recruited. Plasma H(2)S and HCY concentrations were
      determined in all patients and controls. RESULTS: (1) Plasma H(2)S levels were
      significantly lower (P < 0.05) and HCY levels were significantly higher (P <
      0.01) in ever-treated hypertensive patients compared with controls. (2) Plasma
      HCY levels were significantly higher in patients with hypertension history > 6
      months and complicated with CAD compared to patients without CAD. (3) Plasma
      H(2)S concentrations in patients with stroke history > 5 years were significantly
      lower than that in patients without stroke (P < 0.01). Plasma HCY concentrations
      were increased in proportion to stroke history. (4) In ever-treated hypertensive
      patients, plasma H(2)S concentrations in patients with grade 2 and 3 hypertension
      were significantly lower (P < 0.05) and HCY levels significantly higher (P <
      0.01) than that in patients with well-controlled blood pressure. CONCLUSION:
      Hyperhomocysteinemia and the novel signaling gasotransmitter H(2)S might play
      important roles in the pathogenesis and development of hypertension.

PMID- 18341822
TI  - [Hyperinsulinemia induced immune maturation of human monocyte derived dendritic
      cells: bridging between diabetes and atherosclerosis].
AB  - OBJECTIVE: Dendritic cells an hyperinsulinemia are both implicated in the
      pathogenesis of atherosclerosis. The aim of this study is to explore the effect
      of high concentration of insulin on the maturation of monocyte-derived dendritic
      cells (MoDCs) and related signal transduction pathways. METHODS: Human monocytes
      were purified (over 98%) using Anti-CD14 micro-beads and cultured for 5 days with
      DC Cellgro medium containing rhGM-CSF (100 microg/L) and rhIL-4 (20 microg/L).
      Immature DC were then incubated with insulin of various concentrations (0, 1, 10,
      100 nmol/L) for 24 hours in the presence or absence of LY294002 (PI3K inhibitor)
      or PD98059 (MAPK inhibitor). Immunophenotypic expression of CD86 and CD83 were
      detected using flow cytometry. Endocytosis function of the MoDCs was evaluated
      using FITC-Dextran and MoDCs secretion IL-12, IFN-gamma and TNF-alpha were
      measured by ELISA. RESULTS: Insulin induced significantly higher CD83 and CD86
      expressions on MoDCs in a dose-dependent manner. The endocytosis function of
      MoDCs were significantly inhibited and cytokine secretions of IL-12, IFN-gamma
      and TNF-alpha significantly increased by 10 nmol/L and 100 nmol/L insulin. These
      effects could be blocked by the LY294002 and PD98059. CONCLUSION:
      Hyperinsulinemia contributed to atherosclerosis via stimulating immune maturation
      of MoDCs via both PI3K and MAPK pathways.

PMID- 18341823
TI  - [Electrocardiogram analysis in high risk population of unexplained sudden death
      in Yunnan province].
AB  - OBJECTIVE: The purpose of this study was to analyze the electrocardiographic
      features of the people living in the area with high incidence of unexplained
      sudden deaths in Yunnan province. METHOD: The electrocardiograms of 338 residents
      from three villages (Dayao, Ninglang, Heqing) with high incidence of unexplained
      sudden deaths and one control village (Dali) were analyzed [averaged age was
      (33.4 +/- 11.7) years, 175 men and 163 women]. RESULTS: The incidence of cardiac
      arrhythmias was similar low in all groups. The left ventricular hypertrophy was
      observed in 34.6% of residents from Dayao. QTc significantly prolonged in the
      residents from all 3 high incidence areas compare the control area of Dali
      [control (386.8 +/- 27.22) ms, Ninglang (428.92 +/- 25.71) ms, Heqing (440.67 +/-
      28.03) ms, Dayao (417.7 +/- 24.00) ms, P < 0.05 vs. control]. Incidence of U wave
      was significantly higher in Heqing village than that in control village (P <
      0.05). The QUc of these 3 villages was: (613.67 +/- 37.34) ms, (597.19 +/- 46.47)
      ms, (608.59 +/- 39.59) ms respectively, and also significantly longer than the
      control village of Dali (589.33 +/- 41.27) ms (P < 0.05). The typical pattern of
      U wave presents as enlarged U wave and apparent T-U complex. In the 7 residents
      who have the family history of unexplained sudden death, 6 residents have U wave,
      and 4 of them present typical U wave pattern. CONCLUSION: The significant ECG
      changes in villages with high incidence of unexplained sudden death in Yunnan
      province were prolonged QTc, enlarged U wave and apparent T-U complex and these
      ECG features suggested the repolarization abnormalities of the heart in these
      subjects.

PMID- 18341826
TI  - [Progresses of tissue engineering for promoting myocardial regeneration post
      myocardial infarction].

PMID- 18341829
TI  - [Usefulness of galectin-3 expression in the clinical behavior of differentiated
      thyroid carcinoma].
AB  - BACKGROUND AND OBJECTIVE: Our objective was to quantify the galectin-3 (gal-3)
      expression in differentiated thyroid carcinoma and study its relation with the
      clinical behavior of these tumors. PATIENTS AND METHOD: We investigated the
      immunohistochemical reaction of gal-3 in patients with papillary thyroid
      carcinoma (PTC) and follicular thyroid carcinoma (FTC) and performed a
      retrospective study in order to find correlations with clinical features. Gal-3
      expression was studied in 53 differentiated tyroid carcinomas (42 PTC and 11
      FTC), and was related with clinical features: metastases, extrathyroid invasion
      and initial stage in the diagnosis and persistence disease and relapses in the
      follow up. RESULTS: Gal-3 expression positivity in PTC had a median of 60%
      (percentil 25 [p25], 17.5%; percentil 75 [p75], 100%), and was significantly
      higher (p < 0.0001) than in FTC (median, 0%; p25, 0%; p75, 15%). In PTC, gal-3
      expression was significantly higher in advanced stages at the time of initial
      diagnosis (p = 0.014), persistent disease (p = 0.012) and relapses (p = 0.012)
      during the follow up. We did not find any significant association between gal-3
      expression and clinical features of FTC. CONCLUSIONS: Gal-3 is a negative
      prognosis marker in PTC but not in FTC.

PMID- 18341830
TI  - [Adherence and effectiveness of the treatment of latent tuberculosis infection
      with isoniazid for 9 months in a cohort of 755 patients].
AB  - BACKGROUND AND OBJECTIVE: The effectiveness of the treatment of latent
      tuberculosis infection depends on its efficacy, the adherence to treatment and
      patient's risk of tuberculosis. The objective of this study was to evaluate the
      adherence to treatment with daily isoniazid for 9 months, its effectiviness and
      equivalent adherence with daily isoniazid for 6 months so that treatment can be
      as effective as with daily isoniazid for 9 months. PATIENTS AND METHOD: Cohort of
      755 contacts of patients with lung confirmed tuberculosis with latent
      tuberculosis infection treated from 1986 to 2004, classified according to risk of
      tuberculosis disease into converters (high risk), frequent and non-frequent
      contacts. Adherence's rate for daily isoniazid for 9 months is evaluated
      according to percentage of treatment completion and effectiveness achieved is the
      number necessary to treat for preventing one tuberculosis case. Efficacy
      (reduction of morbidity) with isoniazid for 9 months: 93%, and with isoniazid for
      6 months: 69%. RESULTS: Adherence's rate: 53/59 (89.9%; 95% confidence interval
      [CI], 82.1-97.5%) in converters; 305/380 (80.3%; 95% CI, 76.3-84.3%) in frequent
      contacts; and 205/211 (64.9%; 95% CI, 59.6-70.2%) in non-frequent contacts. The
      number necessary to treat with isoniazid for 9 months was 9 for converters, 16
      for frequent contacts, and 79 for non-frequent contacts. Equivalent adherence for
      daily isoniazid for 6 months was 121% for converters, 108% for frequent contacts
      and 87.5% for non-frequent contacts. CONCLUSIONS: For latent tuberculosis
      infection, a 9-month-isoniazid treatment has the highest effectiveness in the
      converters and frequent contacts. Such high effectiveness is impossible to
      achieve with a daily 6-month-isoniazid regimen.

PMID- 18341831
TI  - [High-dose ifosfamide and etoposide regimen as salvage and mobilization therapy
      for patients with lymphoma].
AB  - BACKGROUND AND OBJECTIVE: Several groups have used salvage chemotherapy in
      relapsed or refractory lymphomas to mobilize peripheral blood stem cells. The
      objective of this study was to evaluate the antilymphomatous efficacy, the
      ability of mobilization and the toxicity of a regimen containing high-dose
      ifosfamide, etoposide, methylprednisolone (IFOVM) and granulocyte colony
      stimulating factor (G-CSF). PATIENTS AND METHOD: Twenty-four patients with
      relapsed or refractory lymphoma received IFOVM and G-CSF. The median age was 45
      years and 13 were males. The histologyc subtypes of lymphoma were: diffuse large
      B cell (DLBCL) (n = 15), Hodgkin (n = 2), Burkitt (n = 2), mantle cell (n = 2),
      anaplastic (n = 1), peripheral T-cell (n = 1) and follicular (n = 1). RESULTS:
      Two patients died of sepsis within the pancytopenia period. In 17 (77%) of the
      remaining patients more than 1.5 x 10(6) CD34+ cells/kg (median: 7.7 x 10(6)
      CD34+ cells/kg) were collected. The median time to peripheral blood stem cells
      harvest was 17 (range: 13-24) days and 4 patients required 2 procedures of
      apheresis. Sixteen patients (67%) developed neutropenic fever. The median time to
      achieve granulocyte cell count > 1 x 10(9)/l and platelet count > 20 x 10(9)/l
      was 15 and 16 days, respectively. The only factor predicting successful
      mobilization was the diagnosis of DLBCL (p = 0.04). Ten patients underwent
      peripheral blood stem cells transplantation. CONCLUSIONS: The regimen IFOVM and G
      CSF allows an effective peripheral blood stem cells mobilization in patients with
      lymphoma, particularly in those with DLBCL, but it is associated with significant
      toxicity.

PMID- 18341832
TI  - [Stents and thrombosis].

PMID- 18341833
TI  - [Livedo reticularis and thrombosis].

PMID- 18341834
TI  - [Efficacy and security of tumor necrosis factor antagonists in the treatment of
      rheumatoid arthritis].
AB  - In the last decade, tumor necrosis factor (TNF) antagonists had supposed an
      important therapeutic advance in the treatment of patients with rheumatoid
      arthritis (RA) in both early and established RA. Three agents currently available
      -infliximab, etanercept, and adalimumab--have been designed to modify the
      biologic effects of TNF. Infliximab and adalimumab are monoclonal antibodies,
      whereas etanercept is a soluble protein, with different pharmacokinetic and
      pharmacodynamic properties, conditioning some possible adverse effects. Although
      comparative studies are not available, the 3 drugs have demonstrated efficacy and
      security, with a better quality of life of patients with RA. Infliximab,
      etanercept and adalimumab have been proved alone and in combination with
      methotrexate, with a better therapeutic, clinical, radiological and functional
      response in the group under combined therapy. Both clinical trials and post
      market experience have demonstrated the security of these drugs, minimizing the
      risks with an adequate selection of patients.

PMID- 18341835
TI  - [Lights and shades in the application of new guidelines for the management of
      type 2 diabetes mellitus. Practical advice about combined therapy and insulin
      therapy].
AB  - Type 2 diabetes is a disease with an increasing prevalence due to the ageing and
      sedentary lifestyle of the general population. Its associated with the risk of
      developing a series of chronic complications in mid/long-term. The current
      guidelines recommend certain therapy targets that have proven difficult to
      achieve due to poor compliance or because doctors do not always adhere to expert
      guidelines. The inability to achieve an adequate glycemic control in the course
      of diabetes may result in part from the typical conservative stepwise treatment
      approach that includes monotherapy initiated alter failure of diet and exercise,
      followed by a combination of oral antiglycemic agents, and ultimately insulin
      therapy. With respect to insulin therapy, the availability of different analogues
      as well as the new routes of administration (e.g., inhaled insulin) may allow the
      early introduction of this therapy, which may be more readily accepted by the
      patient.

PMID- 18341836
TI  - [Significance of the insulin resistance in vascular disease associated to
      rheumatoid arthritis].

PMID- 18341837
TI  - [Coexistence of hepatosplenic myeloid metaplasia of donor's cells and graft
      versus host liver disease in a recipient of an allogenic transplant of
      hematopoietic progenitors due to idiopathic myelofibrosis].

PMID- 18341838
TI  - [Community-adquired necrotizing fasciitis by Serratia marcescens].

PMID- 18341839
TI  - [Acute coronary syndrome. Hyperhomocysteinaemia and methylenetrahydrofolate
      reductase c677t mutation with failure in the anticoagulation].

PMID- 18341840
TI  - [Acetabular periprothesic fracture].

PMID- 18341841
TI  - [High incidence rates of inflammatory bowel disease in Navarra (Spain). Results
      of a prospective, population-based study].
AB  - INTRODUCTION: As reflected in the European Collaborative Study on Inflammatory
      Bowel Disease (1991-1993), differences between northern and southern European
      countries in the incidence of ulcerative colitis (UC) and Crohn's disease (CD)
      show a tendency to decrease. No data are available on the current incidence of
      these diseases in Navarre (northern Spain). AIM: To determine the present
      incidence of inflammatory bowel disease (IBD) in Navarra. PATIENTS AND METHODS: A
      prospective, population-based study was performed to determine the incidence of
      IBD in Navarra between 2001 and 2003. Total population: 569,628 inhabitants
      (284,620 males). All cases of IBD diagnosed in any public or private hospital in
      Navarre were included in the study. Crude rates and age- and sex-specific rates
      adjusted to the European standard population were calculated. RESULTS: A total of
      288 cases were diagnosed (UC 176, CD 102, indeterminate colitis 10). Crude rates
      of UC, CD and indeterminate colitis were 10.29, 5.96 and 0.58 cases/100,000
      inhabitants/year respectively (the population aged 0-14 years of age was
      included). Specific rates were 9.57 (95% CI, 7.27-12.57) and 5.85 (95% CI, 3.99
      8.14) cases/100,000 inhabitants/year for UC and CD, respectively. CONCLUSIONS:
      The incidence of UC and CD in Navarra has increased in the last decade, with
      rates close to those of northern European countries and higher than those
      recently published in Spanish prospective studies.

PMID- 18341842
TI  - [The Euro-Wilson project: a European project for the study of Wilson's disease].

PMID- 18341843
TI  - [Pharmacological agents for the treatment of chronic hepatitis B].

PMID- 18341844
TI  - [Phantom tumor of the pancreas].

PMID- 18341845
TI  - [Spontaneous bacterial peritonitis due to Gemella morbillorum in a patient under
      chronic treatment with norfloxacin].

PMID- 18341846
TI  - [Acute hepatitis due to varicella zoster virus].

PMID- 18341847
TI  - [PROLOGO: efalizumab].

PMID- 18341848
TI  - [The lymphocyte: protagonism in the new era of the biological therapies].
AB  - Psoriasis is a systemic type T cell mediated immune system chronic inflammatory
      skin disease. These cells play an important role in the immune system and in the
      inflammatory response that determines the development and maintenance of the
      psoriasis lesions. However, greater understanding of the pathophysiology of this
      disease has led to the development of specific and selective biological
      treatments. Efalizumab is a humanized IgG1 monoclonal antibody that binds to the
      Leukocyte-Function-Associated Antigen 1 (LFA-1). When it binds to the CD11a-
      alpha subunit of LFA1--it inhibits the binding of this ligand to the
      intercellular adhesion molecule 1. This inhibits several processes related with
      the T cells that are fundamental in the pathogenesis of psoriasis: activation of
      the T cells in the lymph nodes, the migration of the T cells towards the dermis
      and epidermis and finally the reactivation of these in the inflammatory focus.
      The clinical studies have demonstrated that efalizumab, administered
      subcutaneously only once a week, provides a clinical benefit as well as
      improvement in the quality of life in patients with psoriasis with chronic,
      moderate or severe plaques. Long-term treatment studies suggest that continuous
      therapy with efalizumab is more beneficial in the maintenance of the improvement
      of the response and demonstrate that efalizumab may be administered safely for
      prolonged periods. Given its efficacy, rapid onset action, safety profile due to
      its selective action mechanism and convenience in its subcutaneous self
      administration weekly, efalizumab offers a new therapeutic option, especially of
      interest for the treatment of psoriasis.

PMID- 18341849
TI  - [Efficacy of short- and long-term efalizumab].
AB  - T cells play an important role in the immune system and in the inflammatory
      response that determines the development and maintenance of psoriasis plaques.
      Better understanding of the pathophysiology of this disease has led to the
      development of specific biological treatments aimed at patients with extensive
      psoriasis. Traditionally, psoriasis has been treated with drugs which, in spite
      of their efficacy, have a toxicity associated to their long-term use. Thus, they
      cannot be used safely, comfortably or efficiently in many patients. Efalizumab, a
      biological agent specifically and selectively directed towards blocking the key
      steps in the pathogenesis of psoriasis, has been shown to be effective and safe
      in the short and long term in the treatment of psoriasis in more than 15 phase I,
      II and III clinical trials. In this article, the results of efficacy at 12 weeks,
      6 months and three years are reviewed. Efalizumab arises as an important addition
      to the dermatological pharmacopoeia for the long-term treatment of psoriasis.

PMID- 18341850
TI  - [Is efalizumab a safe treatment for a chronic disease?].
AB  - Psoriasis is a chronic disease that has a very negative impact on the quality of
      life of those suffering it. Therefore, treatments that make it possible to
      satisfactorily control the disease in the long term and maintain a good safety
      profile are needed. Efalizumab fulfills both requirements. In this article, the
      potential risks involved in treatment with efalizumab, specifically the acute flu
      like syndrome, alterations in laboratory data (leukocytosis, lymphocytosis,
      thrombocytopenia, hemolytic anemia, elevation of alkaline phosphatase and hepatic
      biochemistry), infections, neoplasms, skin disorders related with psoriasis
      (localized papular rash, generalized inflammatory rash, changes in the morphology
      of psoriasis, rebound phenomenon), joint manifestations, acute inflammatory
      polyradiculoneuropathy and hypersensitivity reactions are reviewed. The
      contraindications, presence of antiefalizumab antibodies, their drug
      interactions, use of vaccines and relationship with pregnancy and breast-feeding
      are also discussed. An adequate selection of the patient, detailed information to
      the patient on the benefits and risks and correct knowledge of the potential
      adverse effects by the clinician are essential requirements for satisfactory use
      of efalizumab in long-term continued therapy.

PMID- 18341851
TI  - [Long-term control of psoriasis is necessary].
AB  - Psoriasis is an immune mediated, inflammatory skin condition affecting
      approximately 1.43% of Spanish population. In clinical practice, physicians use
      PASI index to assess the severity. Psoriasis causes physical and mental
      disability comparable to other chronic diseases and affects seriously the
      patients quality of life. For treatment we have different options. Conventional
      systemic treatment such as methotrexate, cyclosporine and acitretin may be
      associated with relevant side effects, and organ toxicity that avoid long term
      therapy. Several psoriasis patients have other comorbid disorders like obesity,
      diabetes, dyslipemia, hypertension and an increased rate of cardiovascular
      disease and metabolic syndrome and these patients need safer treatments. The
      accumulating clinical experience with new therapies consistent on biological
      agents like efalizumab indicates that are effective therapies, with safety
      profile and no evidence of cumulative toxicity that allows a long term use. A
      better control of psoriasis improves patients quality of life.

PMID- 18341852
TI  - [Strategies to improve treatment with efalizumab].
AB  - It is essential to improve the clinical results of efalizumab and to assure that
      it is used under safety criteria in order to obtain a systemic management of the
      treatment. Prior to proposing and prescribing the treatment, the dermatologist
      should make sure that the patient fulfills pills the requirements to be able to
      initiate it and that, on the other hand, there is no serious contraindication
      that may affect its short-to-long term safety. During the course of the
      treatment, some follow-up guidelines should be established that will make it
      possible to compare the evolution of the patient with the general perspectives of
      efalizumab as well as to monitor and manage the most common adverse effects
      associated to its use. Finally, it would be convenient to become familiar with
      the natural course of the disease once the treatment is discontinued in those
      cases in which this action is decided or should be carried out.

PMID- 18341853
TI  - [Which patient is a candidate for treatment with efalizumab and why?].
AB  - With the coming of the biological therapies, long-term maintained control of
      psoriasis is becoming a reality and means a significant improvement in the
      quality of life in some patients with persistent clearing of the disease. This
      result was difficult to obtain previously. Efalizumab, a recombinant IgG1 anti
      CD11a antibody approved for the treatment of psoriasis in moderate-to-severe
      chronic plaques, has an excellent safety profile and its therapeutic results in
      the clinical practice have surpassed the expectations based on the clinical
      trials. At 12 weeks of treatment (when its efficacy should be evaluated), a PASI
      75 response can be expected in 35 to 40% of the patients and a PASI 50 response
      in two thirds of them. This degree of improvement may be maintained and may even
      increase in 80% of the patients, making it possible to achieve an almost complete
      clearing in more than 40% of the patients who continue the treatment over several
      years. Localized, transitory exacerbations may appear, especially in the
      beginning of the treatment, but these can generally be managed in combination
      with another treatment. There may also be generalized inflammatory outbreaks,
      especially in patients with scarce or null response, who require treatment with a
      rapid effect systemic drug at the onset. This is because they may be a prelude to
      the development of rebounds, that may acquire an erythrodermic or pustular
      morphology or be accompanied by arthritis, and which tend to appear after the
      sudden withdrawal of the drug. An adequate selection of the patients may maximize
      the possibilities of success. Patients without arthritis and with stable,
      extensive and non-inflammatory forms of the disease tend to be the best
      candidates. Special attention should be given to the administration of systemic
      agents in transition regimes when efalizumab is introduced or withdrawn. The
      clinical criteria is fundamental to optimize the therapeutic results with
      efalizumab, that may be an attractive challenge but may also be an especially
      satisfactory therapeutic option when long-term control is the disease is
      proposed.

PMID- 18341854
TI  - [My clinical experience with efalizumab in the Hospital of Conxo].
AB  - Psoriasis in plaques is a chronic disease that requires systemic treatment in its
      moderate and severe forms. Because the need for treatment is generally prolonged,
      many medications indicated for its treatment cannot be used continuously and have
      to be replaced by other different drugs, but also with a limited use, both due to
      their possible side effects, their teratogenicity, the time of use and
      accumulated dose, among other reasons. The biological drugs have been designed
      for middle and long term control of the disease. Efalizumab is a drug that has
      been shown to be effective and safe in patients who have moderate-to-severe
      psoriasis. We present our results in a group of 50 patients, our special cases,
      the form in which we have treated the side effects due to Efalizumab and those
      due to the disease.

PMID- 18341855
TI  - [A case of excellent response to efalizumab. Experience in the University
      Hospital of Salamanca].
AB  - Before initiating treatment with efalizumab, or with any other biological
      treatment, it is necessary to use objective assessment techniques that allow us
      to evaluate the activity on course of psoriasis, thus being able to justify the
      indication of biological therapy and to evaluate the percentage of response to
      treatment, loss of response or its possible inefficacy. In spite of its
      limitations, Psoriasis Area and Severity Index (PASI) is the best available
      option. The definition of moderate psoriasis has been proposed as beginning with
      a baseline PASI = 7 while serious psoriasis has a score of, according to the
      different authors, 10 or 12. In the usual clinical practice, other parameters
      must also be evaluated in the definition of the seriousness of psoriasis and in
      the indication of establishing a systemic treatment since some forms of psoriasis
      have a more aggressive course (erythrodermic psoriasis, pustulous psoriasis) and
      there are locations (head, genitals, hands, etc.) that interfere more intensely
      with the quality of life of the patients, with increase of social dysfunction,
      physical incapacity and psychological deterioration. All of the patients treated
      with biological therapy in our hospital site fulfill the criteria established by
      the European Medicines Evaluation Agency (EMEA): adult patients with psoriasis in
      chronic moderate-to-serious ones who have not responded or in its use is
      contraindicated or who do not tolerate another systemic therapy, including,
      cyclosporine, methotrexate or phototherapy.

PMID- 18341856
TI  - [Clinical experience with efalizumab in the Hospital of Cruces].
AB  - Efalizumab (Raptiva) is one of the biological agents approved recently for the
      treatment of patients with moderate-severe psoriasis who have not responded to
      conventional treatments. It is a humanized IgG1 monoclonal antibody which, due to
      its anti-D11 effect, is capable of blocking the endothelial migration and T cell
      activation on the skin, fundamental processes in the etiopathogeny of psoriasis.
      We present the experience we have had in our hospital over the last two years
      with 23 patients who have initiated treatment with efalizumab.

PMID- 18341858
TI  - [Redundant publication: everyone against].

PMID- 18341857
TI  - [Final recommendations to incorporate efalizumab into the clinical practice].

PMID- 18341859
TI  - [Olfactory alterations in allergic rhinitis to pollens and mites].
AB  - INTRODUCTION: In the last 80 years, the presence of allergies has increased among
      Europeans from 0.28% to 14.2%. Allergic rhinitis is the main presentation, rising
      from 18% to 40% of cases. The aim of this study is to demonstrate that allergic
      rhinitis due to pollen and mites has an effect on the olfactory system. MATERIAL
      AND METHODS: We describe the impairment of olfactory function in two groups of
      individuals with allergic rhinitis due to mites or pollen (n = 76; 42 with
      allergy to pollen [48.9%], and 34 with allergy to mites [39%]), compared with a
      group of healthy volunteers (n = 120). Olfactory ability was measured by the BAST
      24 (Barcelona Smell Test) olfactometer comprising 20 odours tested by the forced
      choice method to compare the levels of odour detection (knowing if there is odour
      in the environment), and efficacy (identifying what was smelt). RESULTS: The
      results show firstly that people with allergic rhinitis have a clear, definitive,
      and significant impairment (P >.05) in olfactory levels; secondly, there is a
      tendency towards greater olfactory loss in the case of people with pollen-related
      allergic rhinitis than in those allergic to mites; and thirdly, the different
      odours are affected differently in the 2 groups. CONCLUSIONS: We propose
      consideration of the study of olfactory status in the assessment of patients with
      allergic rhinitis.

PMID- 18341860
TI  - [Unilateral benign choanal polyp: review of 51 patients].
AB  - INTRODUCTION: Choanal polyps are a benign pathology arising in the sinusal mucosa
      and entering the nasal fossa heading for the choana. It is a unilateral condition
      mainly affecting young people. It must be surgically removed, with exeresis of
      both the nasal and the sinusal lesions. MATERIAL AND METHOD: A retrospective
      review has been made of 51 patients treated for choanal polyp at our centre. They
      were diagnosed through physical examination, nasal endoscopy, nasosinusal CT, and
      histological examination of biopsy from the mass in selected cases. RESULTS: The
      choanal polyps originated in the maxillary sinus in 46 cases, in the ethmoidal
      sinus of 5 patients, and only 1 in the sphenoid sinus. Antrochoanal and
      ethmoidochoanal polyps were simultaneously found in 1 patient. Unilateral nasal
      obstruction was the main clinical presentation in our series. Nasal discharge,
      epistaxis, and snoring were other initial clinical findings. Eighty-five per cent
      (39/46) of antrochoanal polyps (ACP) emerged into the nasal fossa through
      Giraldes's accessory orifice, and 15% (7/46) through the natural ostium of the
      sinus. The origin in the maxillary sinus was adequately documented in 18 cases.
      The endoscopic approach was used in 46 patients. Other options employed were the
      Caldwell-Luc approach and a combination of limited antrostomy and endoscopic
      nasal surgery; these were among the first cases seen and therefore the oldest.
      Two of them relapsed and were treated again with an endoscopic nasosinusal
      approach. CONCLUSIONS: Endoscopic nasosinusal surgery is a safe and effective
      option and represents the approach of choice for the treatment of this pathology.

PMID- 18341861
TI  - [Nasosinusal endoscopic surgery as major out-patient surgery].
AB  - INTRODUCTION: Functional endoscopic sinus surgery (FESS) is a useful and
      widespread technique that allows the treatment of a large number of nasal
      pathologies. Nevertheless, although many ENT operations are carried out on an out
      patient basis, FESS procedures commonly require at least 1 day of hospital
      admission in many centres. OBJECTIVES: To evaluate our experience in FESS as day
      case, to study causes of unexpected overnight admission, and to identify any risk
      factors for failing to comply with early discharge. MATERIAL AND METHOD: We
      studied 145 patients consecutively subjected to out-patient FESS procedures for
      chronic rhinosinusitis, antrochoanal polyps, and dacryocystorhinostomy from
      August 2004 to June 2007. We analyzed sex, age, medical history (arterial
      hypertension, asthma, Widal syndrome), pathology, associated septoplasty, extent
      of the surgery, and revision surgery. RESULTS: The re-admission rate was 13.1%
      with the following as the most frequent causes: bleeding (31.6%), requiring only
      observation in over half the cases (ie, without changing the nasal packing), and
      dizziness/weakness (36.8%). Only revision surgery was associated with an increase
      in the re-admission rate (odds ratio, 3.5; 95% CI, 1.2-10.1). CONCLUSIONS: Our
      experience in FESS for out-patient surgery shows a readmission rate of 13.1 %,
      although most cases were related to minor complications. The revision surgery was
      the only variable that could be associated with an increase in re-admission rate.

PMID- 18341862
TI  - [Undiagnosed (corrected) cases of obstructive sleep apnoea syndrome: a new reason
      for involvement of otorhinolaryngologists].
AB  - INTRODUCTION: In Spain there are around 2 million people with obstructive sleep
      apnoea syndrome who should be treated. However, less than 10 % have been
      diagnosed and treated. Untreated patients are associated with a higher risk of
      cardiovascular and neurological complications, higher accident rates, reduced
      quality of life and greater health-care consumption. It is necessary, therefore,
      to reduce these consequences through early diagnosis and treatment. OBJECTIVE: To
      demonstrate the usefulness of a simple series of questions and examination as a
      mechanism to detect patients with undiagnosed obstructive sleep apnoea syndrome,
      in a consultation with a general otorhinolaryngologist. MATERIAL AND METHOD: Five
      hundred two consecutive patients coming to an otorhinolaryngological consultation
      for reasons other than sleep pathology were submitted to a series of questions
      and an examination of upper aerodigestive tract, to search for indications of
      suspected sleep apnoea. For the different clinical and anatomical comparisons, a
      control group of 178 consecutive already-diagnosed patients was used. RESULTS: Of
      the 502 cases, 74 (14.7%) fulfilled the requirements for suspicion and 35 of them
      agreed to take a polysomnograph test (47.29%). Of this group, an apnoea/
      hypopnoea index greater than 5 was found in 24 of the 35 cases (4.78%).
      CONCLUSIONS: The prevalence of obstructive sleep apnoea in the group of patients
      studied is greater than that of the general population. With a simple interview
      and physical examination, a high rate of success can be obtained in the detection
      of undiagnosed sleep apnoea cases.

PMID- 18341863
TI  - [Auditory threshold in professional divers not exposed to noise].
AB  - OBJECTIVES: Otologic and audiometric evaluation of professional divers without
      noise exposure has been carried out to analyze the repercussions of this activity
      on their hearing. MATERIAL AND METHOD: A total of 233 professional divers,
      working in a no noise environment, with an average experience of 9.6 years and
      2074 lifetime dives, in a working depth between 10 m and 27 m, average 4.6 hours
      underwater time were evaluated. This atypical population of divers did not follow
      any decompression schedule and engaged in diving in a purely empirical and
      intuitive fashion. RESULTS: Eighty-nine point two per cent presented symptoms of
      decompression sickness (DCS). Only 19.7% presented a mean hearing threshold below
      20 dB while 73.5% had a mild hearing loss. Significant differences (P < .0001)
      were found in hearing thresholds at 3, 4, and 6 kHz when hearing thresholds were
      grouped by years of experience and diver's age. No such increase was found when
      the sample was grouped by DCS symptoms, vestibular symptoms, number of dives, or
      patent foramen ovale. CONCLUSIONS: The presence of high-frequency sensorineural
      hearing loss in professional divers is related to their age and experience, even
      without a noisy working environment.

PMID- 18341864
TI  - [Peripheral vertigo classification. Consensus document. Otoneurology committee of
      the Spanish otorhinolaryngology society (2003-2006)].
AB  - There are many different vertigo classifications and different denominations are
      frequently used for the same clinical processes. The Otoneurology Committee of
      the Spanish Society for Otorhinolaryngology and Head and Neck Pathology proposes
      an eminently practical classification of peripheral vertigo to facilitate a
      common terminology that can be easily used by the general ENT practitioners. The
      methodology used has been by consensus within our Society and especially among
      the most outstanding work groups in the area of otoneurology in Spain. Initially
      vertigo is divided into single-episode vertigo and recurring attacks of vertigo,
      and these are then sub-divided into 2 groups, depending on whether or not hearing
      loss is present. Acute vertigo without hearing loss corresponds to vestibular
      neuritis and if it is associated with hearing loss, it is due to labyrinthitis of
      different aetiologies and cochleo-vestibular neuritis. Recurrent vertigos without
      hearing loss are classified as induced, either by posture (BPPV) or pressure
      (perilymphatic fistula), or as spontaneous, including migraine-associated
      vertigo, metabolic vertigo, childhood paroxysmal vertigo and vertigo of vascular
      causes (AITs, vertebral-basilar failure). Finally, recurrent vertigo with hearing
      loss includes Meniere's disease and others such as vertigo-migraine (with hearing
      loss), autoimmune pathology of the inner ear, syphilitic infection, and
      perilymphatic fistula (with hearing loss).

PMID- 18341865
TI  - [Fast-growing atypical cervical mass].
AB  - Aneurysms of the jugular vein are an uncommon condition, typical of childhood and
      adolescence although they can appear at any age. Clinically, they normally
      constitute an asymptomatic cervical mass which increases when Valsalva's
      manoeuvre is applied. Doppler echography is the most effective diagnostic test,
      with CT or NMR for doubtful situations. Treatment is conservative except for
      complications or major aesthetic repercussions. We present here the case of a 65
      year-old female patient, and review the literature regarding aneurysms of the
      jugular vein.

PMID- 18341866
TI  - [Usefulness of video-assisted cervicotomy on the extraction of foreign bodies].
AB  - Foreign bodies located in the upper aerodigestive tract, if not diagnosed and
      taken out speedily, may be the cause of great morbimortality. We present a female
      patient who arrived at the emergency department reporting she had swallowed a
      fish bone; it was finally located in the pre-vertebral muscle at the level of C3
      C4, where it had entered from the oesophagus at 2 cm from the superior
      oesophageal sphincter. We used a cervicotomy assisted by endoscopy, showing a new
      application for videoendoscopy.

PMID- 18341867
TI  - [Image-based diagnosis of cervical hibernoma].

PMID- 18341868
TI  - [Comments on the physiology of single-ossicle transmission systems].

PMID- 18341871
TI  - [Is parapneumonic empyema increasing?].

PMID- 18341872
TI  - [Is the incidence of parapneumonic pleural effusion increasing?].
AB  - INTRODUCTION: Streptococcus pneumoniae is the microorganism most frequently
      associated with complicated pleural effusion. After the introduction of the
      heptavalent pneumococcal vaccine, there was a decline in the incidence of
      invasive pneumococcal disease and, to a lesser extent, in that of pneumonia.
      However, the incidence of empyema apparently increased. The antipneumococcal
      heptavalent vaccine was introduced in Spain in 2001. OBJECTIVES: To determine
      whether the incidence of pleural effusion secondary to pneumonia has increased in
      hospitalized patients and to examine the possible influence of the
      antipneumococcal heptavalent vaccine on the incidence rate of parapneumonic
      effusions. PATIENTS AND METHODS: Patients aged less than 16 years old admitted to
      our hospital with a diagnosis of pneumonia between 1999 and 2005 were
      retrospectively reviewed. We calculated the annual incidence rate of pleural
      effusion with respect to the total number of patients admitted with pneumonia and
      with respect to patients considered to have probable bacterial pneumonia, based
      on previously established criteria. RESULTS: A total of 337 patients were
      analyzed, of which 213 (63.2%) met the criteria for a diagnosis of probable
      bacterial pneumonia. Pleural effusion was found in 34 patients (15.9%), and 13 of
      these effusions (38%) were complicated. No clear trend was detected in the annual
      incidence of probable bacterial pneumonia per 100 admitted patients, although the
      highest numbers were detected in the last two years of the study period. The
      percentage of complications (effusions) remained constant (mean: 16.28%). No
      differences were found in the effusion rate between vaccinated and unvaccinated
      patients (12.5% vs 18.6%). CONCLUSIONS: The trend in the incidence of
      parapneumonic pleural effusions was parallel and proportional to that of probable
      bacterial pneumonia.

PMID- 18341873
TI  - [Increase in the incidence of bacterial pneumonia between 2001 and 2004].
AB  - AIM: To study patients with typical community-acquired pneumonia (CAP) admitted
      to our hospital between 2001 and 2004 in order to analyze the incidence of this
      disease in our health area during this period. METHODS: A retrospective study was
      performed of patients with CAP admitted to our hospital from 2001 to 2004. Only
      those patients who fulfilled the criteria for typical pneumonia of possible
      bacterial origin based on clinical and radiological features and laboratory data
      were included. The annual incidence rates of CAP were analyzed using demographic
      data from our health area and from all children admitted to the infectious
      diseases unit of our hospital during this period. RESULTS: During the study
      period, 569 children were diagnosed with typical CAP: 116 in 2001, 133 in 2002,
      154 in 2003 and 166 in 2004. The incidence rate was 1.3 cases/1,000 children
      under 14 years old/year in 2001, 1.51 in 2002, 1.69 in 2003 and 1.72 in 2004.
      These findings represent an increment of 25% in the incidence per
      1,000/children/year and an increment of 53% in the incidence per 100 children
      admitted to our unit. Blood cultures were performed before antibiotic therapy was
      administered in 487 patients and were positive in 22 (4.5%). Streptococcus
      pneumoniae was isolated in 21 patients and Streptococcus pyogenes in one. Chest
      radiographs revealed lobar consolidation in 95% of the patients and 15 %
      developed pleural effusion. CONCLUSIONS: Cases of CAP of probable pneumococcal
      etiology increased in our health area during the study period. The number of
      complicated cases also increased.

PMID- 18341874
TI  - [Total white blood cell count, erythrosedimentation rate and C-reactive protein
      for the detection of serious bacterial infections in 0- to 90-day-old infants
      with fever without a source].
AB  - INTRODUCTION: Total white blood cell count (WBC), erythrosedimentation rate (ESR)
      and C-reactive protein (CRP) are frequently used by primary care physicians
      attending infants < 90 days old with fever without localizing signs to
      distinguish those with a serious bacterial infection (SBI). The main objective of
      this study was to obtain the diagnostic values of these parameters in infants
      with fever. PATIENTS AND METHODS: We analyzed previously healthy infants aged 0
      to 90 days old and fever with no source of infection admitted to the emergency
      room and/or hospitalized. The main outcome measure was the presence or absence of
      a SBI (urinary tract infection, bacteremia, meningitis, pneumonia, enteritis) and
      diagnostic values of WBC, ESR and CRP. RESULTS: A total of 103 infants met the
      inclusion criteria. Of these, 22 infants (21.3%) had a SBI, the most common being
      urinary tract infection. Absolute neutrophil count (ANC) and WBC had an area
      under the ROC curve (AUC) of 0.6 (95% CI: 0.46-0.73) and 0.55 (95% CI: 0.44-0.68)
      respectively. An ANC>or=10,000/microl had a sensitivity and specificity of 9%
      (95% CI: 1-21) and 92.5% (95% CI: 86-98) respectively. A WBC>or=15,000/microl had
      a sensitivity and specificity of 13.6% (95% CI: 1-28) and 85% (95% CI: 77-93)
      respectively. CRP showed an AUC of 0.71 (95% CI: 0.55-0.86) and a best cut-off
      point of 2 mg/dL (sensitivity 53% [95% CI: 29-76] and specificity of 85% [95% CI:
      75-94]). ESR>or=20 mm/hour had an AUC, sensitivity and specificity of 0.53 (95%
      CI: 0.37-0.7), 38% (95% CI: 16-62) and 75% (95% CI: 65-85) respectively.
      CONCLUSIONS: None of these parameters alone, commonly used by physicians, is a
      reliable diagnostic tool to rule out SBI in infants<90 days old with fever
      without source of infection.

PMID- 18341875
TI  - [Macrophage activation syndrome and juvenile idiopathic arthritis. A multicenter
      study].
AB  - INTRODUCTION: Macrophage activation syndrome (MAS) is a severe complication of
      systemic juvenile idiopathic arthritis (sJIA). OBJECTIVE: To describe the
      clinical characteristics and outcome of patients diagnosed with MAS in Spanish
      pediatric rheumatology units. PATIENTS AND METHOD: A protocol for data collection
      was designed and distributed to pediatricians and rheumatologists attending
      children with rheumatic diseases. RESULTS: Information was available from 31
      patients (16 boys and 15 girls) who had 37 MAS episodes. Twenty-seven children
      had only one episode, three had two episodes and one had four episodes. The
      interval between episodes ranged from 1 to 33 months. The median age was 5.9
      years (range 1-23). MAS was the initial manifestation of sJIA in nine patients.
      The most frequent symptom was fever (97%), followed by skin rash (49%), central
      nervous system dysfunction (41%), and gastrointestinal abnormalities (15%).
      Abnormal laboratory findings included thrombopenia (78%) and elevated levels of
      hepatic enzymes (70%). Hemophagocytosis was confirmed in 16 of 30 bone marrow
      samples evaluated, 15 with cyclosporine A and six with etoposide. All episodes
      but one were treated with steroids. One patient received a liver transplant
      before diagnosis. The mortality rate was 6.5% (2/31). CONCLUSION: MAS is a
      severe, potentially lethal, complication of sJIA. The clinical and laboratory
      abnormalities characteristic of sJIA complicate its diagnosis. The earliest and
      most frequent findings were decreased in platelet count and elevation of hepatic
      enzymes. A high degree of suspicion as well as early diagnosis and prompt
      treatment are essential in this disease.

PMID- 18341876
TI  - [Design and validation of a dosing algorithm for vancomycin in premature
      neonates].
AB  - INTRODUCTION: Inappropriate use of vancomycin contributes to the development of
      resistant bacteria and jeopardizes the safety and effectiveness of treatment. The
      aim of this article was to design and validate an empirical dosing algorithm for
      vancomycin in premature neonates according to their population-based
      pharmacokinetic characteristics. PATIENTS AND METHODS: We performed a
      retrospective analysis of 129 serum samples from a cohort of 53 neonates.
      Homogeneous population groups were identified both from their individual
      pharmacokinetic parameters and from their biometric characteristics. The design
      of the dosing algorithm was based on simulation of the serum vancomycin
      concentration that would be reached with several different doses. The algorithm
      was validated in another cohort of 30 neonates and 108 serum samples. RESULTS:
      Introduction of the algorithm significantly increased the percentage initial
      values obtained with correct minimum and maximum concentrations in the first
      monitoring round (p<0.05). The mean number of serum samples obtained per patient
      for treatment monitoring was significantly reduced (3.6+/-2 vs. 4.9+/-3).
      CONCLUSIONS: The implantation of the dosing algorithm for vancomycin in premature
      neonates increased the efficiency of treatment, reduced monitoring requirements,
      and optimized serum vancomycin concentrations from the start of treatment.

PMID- 18341877
TI  - [Staphylococcal scalded skin syndrome].
AB  - INTRODUCTION: Staphylococcal scalded skin syndrome is a rare disease caused by
      Staphylococcus aureus that produces exfoliative toxins. There are few
      epidemiological data in our environment. PATIENTS AND METHODS: We present an
      observational cohort study. We review the cases of staphylococcal scalded skin
      syndrome monitored at La Paz Children Hospital during the last ten years (January
      1997 to December 2006). RESULTS: We obtained 26 patients, 7 in the first 5 years
      and 19 more in the following years. The mean age at diagnosis was 19 months. Four
      cases (15%) occurred during the neonatal period. Sixty-seven percent of the cases
      were diagnosed during spring and summer. Main clinical signs were: erythroderma
      with blisters and posterior desquamation (100%), perioral fissures (54%), fever
      (46%), conjunctivitis (42%) and palpebral edema (31%). No significant increases
      in leukocytes (mean: 11,341/.l) or C-reactive protein (mean: 9 mg/l) were found
      on blood analysis. Diagnosis was made by clinical findings. S. aureus was
      isolated in nasal or conjunctival samples on 59% of cases. All strains were
      sensitive to cloxacillin, clindamycin and vancomycin. The patients were treated
      with cloxacillin with good progress. CONCLUSIONS: Staphylococcal scalded skin
      syndrome seems to be more common in the last few years. It must be suspected in
      children with acute erythroderma and perioral or conjunctival lesions. Treatment
      with cloxacillin leads to healing without sequelae.

PMID- 18341878
TI  - [Economic impact of rotavirus vaccination in Panama].
AB  - INTRODUCTION: Rotavirus (RV) gastroenteritis (GE) causes a significant health and
      economic burden in Panama. The main objective of this study is to estimate the
      healthcare costs and the cost-effectiveness of vaccination in Panama from the
      societal perspective. METHODS: An economic model was constructed, using published
      epidemiological data, country-specific cost estimates, and vaccine efficacy data.
      The main outcome measures were disease burden, economic burden and the
      incremental cost-effectiveness ratio (US$/DALY and US$/life saved) of
      vaccination. RESULTS: In Panama, among children during the first five years of
      life, it is estimated that due to RV GE, 283 per 1,000 have a clinic visit, 24
      per 1,000 are hospitalized, and 0.53 per 1,000 die. For every 1,000 children
      born, RV infection results in US$16,463 in total costs during their first five
      years of life. An estimated US$862,388 may be spent annually on treatment of
      outpatient and hospitalized cases in Panama. Vaccination would prevent 65% of the
      associated deaths, 68% of hospitalizations, 69% of outpatient visits and 65% of
      associated DALY (Disability Adjusted Life Years). From the societal perspective,
      RV vaccination produces a cost-effectiveness ratio of US$487 per DALY when the
      price of the vaccine is US$7.50 per dose. CONCLUSIONS: Vaccination can
      effectively reduce the disease burden and healthcare costs of RV GE in Panama.

PMID- 18341879
TI  - [Hepatitis B serological markers in children adopted from Russia and Ukraine].
AB  - OBJECTIVE: To determine the prevalence of the hepatitis B virus (HBV) infection
      and to verify the immunization status against HBV of children adopted from Russia
      and Ukraine. PATIENTS AND METHODS: Cohort study of 102 children (58.8% boys)
      adopted from Russia (90) and Ukraine (12) between 2002 and 2007. All children had
      medical records that certified they had received 3 doses of HBV vaccine from the
      birth country. They were evaluated within 2 weeks of their arrival (mean age of
      28.3 months; range, 12 to 88 months) according to a standard protocol that
      includes the hepatitis B serological markers, surface antigen (HBsAg), core
      antibody (HBcAb), and surface antibody (HBsAb). RESULTS: All children were
      negative for HBsAg and HBcAb (prevalence of active or previous HBV infection,
      0%), and 78 (76.5%) showed a protective antibody response (HBsAb>or=10 mIU/ml)
      due to HBV vaccination. The results are contrasted with those observed by other
      researchers. CONCLUSIONS: We show that children adopted from Russia and Ukraine
      have a relatively high prevalence of protective immunity due to effective HBV
      vaccination. Therefore, we recommended determining the 3 serological markers for
      HBV (HBsAg, HBcAb, and HBsAb). Using this, we may detect an active infection or
      other infection risks, and we know the immunization status. Thus we can assess
      the need for retest, and provide criteria for individualized vaccinations, which
      could avoid generalized HBV vaccination in this specific population of
      internationally adopted children.

PMID- 18341880
TI  - [Low stature in males with normal phenotype and 45,X/46,XY mosaicism].
AB  - There is wide variation in the clinical expression of 45,X/46,XY mosaicism.
      Ninety percent of prenatally diagnosed boys have normal male phenotype at birth,
      while those diagnosed postnatally show a wide spectrum of phenotypes, ranging
      from Turner syndrome, mixed gonadal dysgenesis, and male pseudohermaphroditism to
      apparent normality. We report the clinical, cytogenetic, endocrinologic and
      histologic findings in three boys with an apparently normal male phenotype and
      45,X/46,XY mosaicism who were diagnosed postnatally because of their short
      stature. With the exception of one patient with Turner stigmata, no other
      abnormal features were found. No correlation between the proportion of 45,X/46,XY
      cell lines in blood, gonads and phenotype was found. Both prenatally and
      postnatally diagnosed boys with normal male phenotype must be followed-up because
      they can develop late-onset abnormalities, such as dysgenetic testes leading to
      infertility or neoplastic transformation, and short stature, which could be
      improved with growth hormone therapy.

PMID- 18341881
TI  - [Tumor necrosis factor receptor-associated periodic syndrome].
AB  - Tumoral necrosis factor receptor-associated periodic syndrome (TRAPS) is an
      autosomal dominantly inherited disease belonging to the hereditary periodic fever
      syndromes, which are the main subgroup among systemic autoinflammatory diseases.
      TRAPS is characterized by prolonged and recurrent inflammatory attacks associated
      with fever and an acute phase reaction. Articular, cutaneous, ocular and
      abdominal symptoms may also be present. We describe the case of a 4-year-old boy
      with recurrent inflammatory episodes, fever and cutaneous symptoms who was
      diagnosed with TRAPS. We review the clinical and laboratory findings, genetic
      diagnosis, and treatment approach in this disease.

PMID- 18341882
TI  - [Scrotal hair in infants].
AB  - The presence of pubic hair is exceptional in healthy infants of both sexes. In
      most of the cases described in the literature, the process was self-limited and
      no etiology was found. Nevertheless, in some patients, this finding has been
      associated with other manifestations of hyperandrogenism related to potentially
      serious diseases such as congenital adrenal hyperplasia or virilizing tumors. In
      the present article, we describe seven infants followed-up in the Pediatric
      Endocrine Clinic because of scrotal hair. In all patients, the process was self
      limited and resolved spontaneously and no hormonal or developmental alterations
      were observed. Key words: Scrotal hair, infants, virilization.

PMID- 18341883
TI  - [Program of sanitary education for people with autistic spectrum disorder].
AB  - INTRODUCTION: Autism is a developmental disorder that it is characterized by a
      qualitative alteration of social interaction, communication and repetitive and
      stereotyped behaviours, interests and activities. Recent studies about health are
      showing that people with autism have lower hope of life. Among other causes,
      difficulty to identify and to communicate uneasiness and resistance to allow
      medical explorations are important factors to consider. AIMS: To design and to
      implant a specific program for people with Autistic Spectrum Disorder (ASD) with
      the objective of habituating them to the medical explorations so that they admit
      it and collaborate, facilitating the sanitary personnel's work. Our aim was to
      evaluate the effectiveness of the program and the maintenance of the potentials
      improvements. METHOD: Our sample was formed by twenty-two children with ASD (mean
      chronological age, 9;10 years). A quasi-experimental design of interrupted
      temporary series was carried out. VARIABLES: two grouping variables (clinical
      characteristics of the groups about QI and about linguistic abilities) as
      dependent variable a measure of percentage of success has been used through an
      observation protocol designed for this program. RESULTS: Improvements in all the
      groups. Results are not conditioned neither for the level of intellectual
      abilities (IQ) neither for the existence or not of linguistic abilities.
      Likewise, it is found that carrying out maintenance sessions in period of seven
      weeks allows to maintain long term achievements reached by the program. However,
      we found that those children which were severely impaired could obtain more
      benefit from more frequent maintenance sessions.

PMID- 18341884
TI  - [Why are pediatric empyemas on the increase in Spain?].
AB  - There is a widespread perception among Spanish pediatricians that the incidence
      of empyema has significantly increased in the last few years, even though the
      objective information available is limited, and there is no specific active
      epidemiological surveillance system for this condition. In the present article,
      we review the situation of empyema in Spain, and discuss the main hypotheses put
      forward in the international literature to explain this increase, as well as the
      limitations of the sources available. Despite the scarcity of information, we
      draw the following conclusions: 1) the incidence of pediatric empyema is
      increasing in Spain, both generally and when caused by pneumococcus in
      particular; 2) the reason for this increase remains unknown, and to date no firm
      link has been established between this phenomenon and the heptavalent conjugate
      pneumococcal vaccine; and 3) this situation justifies the establishment of
      prospective systems for the surveillance and control of empyema and, once again,
      highlights the importance of developing active surveillance systems for
      pneumococcal disease.

PMID- 18341885
TI  - [Evaluation of energy expenditure in children. Physiological and clinical
      implications and measurement methods].
AB  - The present article reviews the importance of the study of energy metabolism and
      its methods of assessment in children. Classically, energy requirements have been
      assessed by predictive equations based on anthropometric data. However, there are
      several physiologic and pathogenic states that may cause discrepancies between
      estimated and real values and consequently direct measurements of energy
      expenditure should be used. The gold standard to assess total energy expenditure
      during prolonged periods is the doubly labeled water method, which is mainly used
      for research studies. The best approach for resting energy expenditure
      determination in the clinical setting is indirect calorimetry. However, this
      method does not provide data on energy consumption under free-living conditions
      and its use in some critical care patients is restricted by technical
      limitations. Several other approaches to assess activity have been developed,
      based on heart rate, body temperature measurements, motion sensors and combined
      methods.

PMID- 18341886
TI  - [SEN1500: design and implementation of a registry of infants weighing less than
      1,500 g at birth in Spain].
AB  - OBJECTIVE: To design and implement a registry of infants weighing less than 1,500
      g at birth in Spain. MATERIAL AND METHODS: Prospective, cohort, multicenter
      study. All live born infants weighing less than 1,500 g in several voluntarily
      participating neonatal units in public and private hospitals were included.
      RESULTS: In the first 4 years of the registry (2002 to 2005), 9,638 very-low
      birth-weight infants were born in the 65 neonatal units that have so far joined
      the program. CONCLUSIONS: The goal of very-low-birth-weight infant databases is
      to try to improve the quality and safety of the medical care given to these
      newborns and their families. This type of program helps to coordinate and promote
      several areas, including those of health education, training of medical staff,
      research and development, surveillance and quality improvement.

PMID- 18341887
TI  - [Pulmonary hypertension associated with vertically transmitted HIV infection in
      an adolescent girl].

PMID- 18341888
TI  - [Pseudocoarctation of the aorta associated with a retroaortic innominate vein].

PMID- 18341889
TI  - [Therapeutic fiberoptic bronchoscopy in the pediatric intensive care unit].

PMID- 18341890
TI  - [Spontaneous chylothorax in a 16-month-old child].

PMID- 18341891
TI  - [Unilateral nonsyndromic cryptophthalmos].

PMID- 18341892
TI  - [Henoch-Schonlein purpura and Chlamydophila pneumoniae].

PMID- 18341893
TI  - [Hypertrophic myocardiopathy associated with oral corticosteroids in an infant
      with cutaneous hemangioma].

PMID- 18341894
TI  - [Generalized urticarial reaction after the use of baby wipes].

PMID- 18341895
TI  - [Hypoferritinemia and tics. An incidental or causal association?].

PMID- 18341896
TI  - [Type I neurofibromatosis and school phobia].

PMID- 18341897
TI  - [Training in breast reconstruction and oncoplastic surgery].

PMID- 18341898
TI  - [Is there a minimum number of lymph nodes that should be examined after surgical
      resection of colorectal cancer?].
AB  - Metastasis to regional lymph nodes, after distant metastasis, is the most
      important prognostic factor of colorectal carcinomas. It is also of primary
      importance in decisions related to the administration of adjuvant treatments.
      Most scientific associations recommend the examination of at least 12 lymph nodes
      for the reliable determination of the absence of nodal metastases. We performed a
      literature review on lymph node recovery in order to determine whether 12 is the
      minimum and optimal number of lymph nodes to be examined after colorrectal cancer
      surgery. The differences between authors suggest that an optimal number of lymph
      nodes to be examined after colorectal cancer surgery probably does not exist and
      depends on many factors. Thus, recovering as many lymph nodes as possible seems
      to be a good option.

PMID- 18341899
TI  - [Society and surgery. Burnout and surgeons].
AB  - Burnout syndrome is a mental and emotional state of tiredness, characterised by
      feelings of emptiness and negative attitudes to work and life. It appears
      particularly in care professionals associated with human interactions, and starts
      progressive, affecting the professional as well as the organisation. It is
      currently the most common cause of absence from work. Its incidence among doctors
      is about 50%, but, despite being considered a high risk group, its incidence and
      consequences among surgeons is still unknown. The causal factors are analysed and
      coping strategies are offered to be able to control the problem.

PMID- 18341900
TI  - [Arterial trauma in hip arthroplasty].
AB  - INTRODUCTION: Arterial injuries due to total hip arthroplasty can be a serious
      complication. The risk of vascular injury is related to proximity of the
      structures, tractions, and the aggressive use of instruments. OBJECTIVES: To
      analyze the frequency, injury mechanism, clinical presentation and therapeutic
      options in this kind of injury. PATIENTS AND METHOD: A group of 4162 patients
      subjected to total hip arthroplasty between 1986 and 2006 (reinterventions 7.2%).
      We describe 8 cases (5 women and 3 men) with a mean age of 61 years
      (reinterventions 50%). The vascular surgery was performed at less than 1 hour (n
      = 4), 6 hours (n = 2), 16 hours (n = 1) and 20 days (n = 1). RESULTS: The most
      frequent locations were external iliac artery (n = 3), common femoral (n = 3),
      internal iliac (n = 1) and deep femoral (n = 1). The clinical presentation was,
      internal bleeding (50%), acute limb ischemia (37%) and subacute limb ischemia
      (13%). The surgical interventions were bypass (50%), arteriorrhaphy (25%),
      primary repair (12.5%), and thrombectomy and patching (12.5%). One case was
      reoperated 6 years later, as we found a false anastomotic aneurism in a previous
      ilio-femoral bypass. The death and amputation rates were 0%. CONCLUSIONS:
      Although these injuries are rare, they involve a life-threatening complication.
      The external iliac artery/common femoral artery are the most frequent location.
      Most patients required a bypass, although the surgical technique depends on the
      injury location.

PMID- 18341901
TI  - [Home treatment of patients with pancreatic fistula].
AB  - INTRODUCTION: Hospital-at-home (HaH) has been previously described as a useful
      model to shorten length of hospital stay. Nevertheless, few experiences have been
      reported on the effectiveness of this scheme in patients with postoperative
      complications. We described the results of home management of patients with
      pancreatic fistula. PATIENTS AND METHOD: A retrospective analysis was performed
      on the clinical data more six patients with postoperative pancreatic fistula
      attended in our hospital-at-home unit. RESULTS: All patients were male with ages
      ranging from 42 to 72 years (mean 59). The average hospital stay was 53 days
      (range 27 to 91). All patients, but one, presented pancreatic drainage more than
      100 mL at the time of HaH admission. During HaH period hospital level treatments
      such as complex cures, intraabdominal lavages, specific laboratory tests,
      intravenous antimicrobial therapy and CT scanning were performed. The average
      time to closure of fistula was 93 days, of which 38 (41%) days were spent at
      home. At the end of HaH period all patients recovered and expressed a high degree
      of satisfaction. CONCLUSIONS: Our data suggest that hospital-at-home is an
      effective model to shorten length of hospital stay in selected patients with
      postoperative pancreatic fistulas.

PMID- 18341902
TI  - [Role of intra-operative echography and computed tomography with multiple
      detectors in the surgery of hepatic metastases: a prospective study].
AB  - OBJECTIVES: To study the performance of the intraoperative ecography in the
      diagnosis of new liver metastases in the era of computerized tomography (CT) with
      multidetectors and its impact on the surgical operation. PATIENTS AND METHOD:
      Between February 2005 and April 2006 patients with resectable liver metastases
      where studied prospectively in a multidisciplinary meeting (surgeons,
      radiologist, oncologist). The preoperative CT findings were compared with the
      intraoperative findings and ultrasound study and the results of the surgical
      operation. RESULTS: Forty-five candidates for curative surgery had a total of 171
      hepatic lesions. CT correctly detected 115 lesions with a sensitivity of 67%, and
      a positive predictive value of 97%, with a false negative rate of 33% and false
      positive rate of 2%. In 5 patients intraoperative findings were the cause of
      changing the surgical procedure, three patients were unresectable (rate of
      resectability of 93%) and two patients needed a larger hepatic resection.
      CONCLUSIONS: CT with multidetectors and multidisciplinary meetings are the most
      important factors in the decision making of surgery of liver metastases with a
      high resectability rate. Intraoperative ecography is useful for the detection of
      10% more liver metastases, but rarely involves a change in the surgical
      procedure.

PMID- 18341903
TI  - [Radical resection of a hilar cholangiocarcinoma. Indications and results].
AB  - OBJECTIVE: The objective of the study is to review our experience in the surgical
      treatment of Klatskin tumours, after the systematic application of the current
      concepts of radicalism. Sixty-one patients resected using these criteria are
      presented. PATIENTS AND METHOD: We have studied 154 patients. Surgery was ruled
      out in 59 (41%) of them, and a liver transplant was performed on 9; of the 86
      patients operated on, 25 were resectable. Resectability was 71% (of the 86
      patients operated on) and was 39% of the total patients. The results during two
      periods are compared, 1989-1998 (pre-99) and 1999-2007 (post-99). RESULTS: On
      comparing the two periods, resectability increased from 26% to 53% (p = 0.01),
      the percentage of exploratory laparotomies decreasing (pre: 45% vs post: 22%; p =
      0.04). Hepatectomy was performed in 53 cases (87%), being most frequent post-99
      (pre: 66% vs post: 91%; p = 0.02). Resection of the caudate was performed in 48
      cases (90%), being most frequent in the post-99 period (pre: 40% vs pos: 89%; p =
      0.005). Post-operative morbidity was 77%, with 28% the patients being re-operated
      on, and the post-operative mortality was 16.4%, with no significant differences
      between the periods. Actuarial survival at 5 years increases in the post-99
      period (pre: 26% vs post: 51%; p = 0.06). CONCLUSIONS: Adequate staging,
      associated with an aggressive surgical strategy can achieve a greater than 50%
      resectability rate. The post-operative morbidity and mortality of this strategy
      is high, but the survival that it achieves justifies this.

PMID- 18341904
TI  - [Pericardial window by videothoracoscope in the treatment of pericardial effusion
      and tamponade].
AB  - INTRODUCTION: Malignancies are the most common causes of pericardial effusion
      (PE) or tamponade (PT). Lung and breast carcinoma are the most frequent. The
      treatment of PE consists in the performance of drainage and/or pericardial window
      (PW) usually subxiphoid. In the present study we describe our experience with the
      PW by videothoracoscopic (VATS) approach, a procedure scarcely referred to in the
      literature. OBJECTIVE: To evaluate the efficacy of the PW by videothoracoscopic
      (VATS) approach in the treatment of PE and/or PT. PATIENTS AND METHOD:
      Retrospective study of 12 patients with PE submitted to PW by VATS in a period of
      10 years, since February 1994 to October 2004. The surgical procedure employed
      was VATS, under general anesthesia, selective intubation and lateral decubitus.
      We systematically performed a PW anterior to phrenic nerve and studied pleural
      and pericardial fluids. Talc pleurodesis was added if neoplastic pleural effusion
      was objectived by a previous needle thoracocentesis and cytological analysis of
      pleural fluid. A single chest drain (24 F) was inserted after surgery, and
      removed when daily debit was under 100 ml. RESULTS: 12 patients were operated on,
      4 men and 8 women, mean age of 58.6 years (range, 32-78). There was no surgical
      mortality. There were 8 cases of PT. The causes of PE were: breast carcinoma in 8
      cases, lung carcinoma in 3 cases and infectious origin in one case. Mean duration
      of surgical procedure was 30 minutes. All the patients had concomitant pleural
      effusion. Surgical approach was by the left side in all the cases. Talc
      pleurodesis was added in 8 cases of the 12 that had pleural effusion, in the 8
      cases cytological analysis had shown paraneoplastic origin. Chest drain was
      removed after a mean period of 3.5 days. There was no mortality associated with
      the procedure. Mean stay was 3.8 days. Mean survival was 12 months for breast
      cancer patients and 4 months for lung cancer. CONCLUSIONS: PW by VATS is a
      suitable procedure for the management of massive PE or PT. In our experience this
      procedure showed no mortality and minimal morbidity, providing symptomatic
      improvement (in PE and pleural efusion) in all the patients. This approach also
      makes possible the study of pleural cavity, the obtaining of parietal pleura
      samples and, if necessary, the performance of talc pleurodesis.

PMID- 18341905
TI  - [Splenic epidermoid cyst].

PMID- 18341906
TI  - [Primary actinomycosis of the abdominal wall].

PMID- 18341907
TI  - [Acute surgery 72 hours after an acute myocardial infarction: what do we do?].

PMID- 18341908
TI  - [Mediastinal ganglioneuroma, a fortuitous finding in lung metastasectomy and
      liver germ cell tumour].

PMID- 18341909
TI  - [Small (oat)-cell carcinoma of the gastrointestinal tract].

PMID- 18341910
TI  - [Hepatic rupture associated with HELLP syndrome].

PMID- 18341911
TI  - [Horner syndrome and central line septic phlebitis: two uncommon complications
      after inserting central venous lines].

PMID- 18341912
TI  - [Iatrogenic perforation of the colon: could it be a conservative option?].

PMID- 18341914
TI  - [Body packer: a review and experience in a reference hospital].

PMID- 18341915
TI  - [Respiratory viruses: the most common, the most often overlooked].

PMID- 18341916
TI  - Evaluation of liquid biphasic Granada medium and instant liquid biphasic Granada
      medium for group B streptococcus detection.
AB  - INTRODUCTION: Group B streptococci (GBS) are transmitted from the mother to the
      newborn. Prevention of neonatal infection is achieved by intrapartum prophylaxis
      given to mothers colonized with GBS at 35 to 37 weeks of pregnancy. MATERIALS AND
      METHODS: Liquid biphasic Granada medium (LB) and instant liquid biphasic Granada
      medium (ILB) were evaluated for GBS detection. Vaginal swabs obtained from 300
      women were inoculated onto LB or ILB, or onto Todd-Hewitt broth and analyzed with
      the ATB system (comparison method). RESULTS: Prevalence of GBS was 20% (61/300).
      LB and Todd-Hewitt with ATB detected GBS in 20% of women, and ILB in 19% of
      women. No growth was observed at four hours in any of the media studied. At 10 h
      and 14 h, identification of GBS was possible in 43/300 (14%) and 53/300 (18%) of
      ILB cultures, respectively, and in 32/300 (11%) and 46/300 (15%) of LB cultures.
      CONCLUSION: All the media used are suitable for GBS detection. The majority of
      GBS were identified in ILB and LB cultures at 10 h and 14 h.

PMID- 18341917
TI  - [Clinical and epidemiological characteristics of respiratory infections caused by
      human metapneumovirus in pediatric patients].
AB  - INTRODUCTION: Human Metapneumovirus (hMPV) was first identified in 2001 in
      respiratory samples from children and adults with acute respiratory tract
      infection. The aim of this prospective study was to determine the clinical and
      epidemiological characteristics of pediatric patients with an acute respiratory
      tract infection and exclusive isolation of hMPV in respiratory samples (December
      2005-January 2007). MATERIAL AND METHODS: All respiratory tract samples were
      submitted to rapid antigen detection against respiratory syncytial virus (RSV)
      and influenza A and B viruses. To isolate respiratory viruses, samples were
      inoculated in various cell lines using the shell vial culture assay. To isolate
      hMPV, the LLC-MK2 cell line was used. Only antigen-negative samples were studied
      for the presence of hMPV. RESULTS: Over the study period, 32 hMPV were isolated
      from different patients, accounting for 1.7% of all samples studied for this
      virus (only RSV-negative samples, 1,791) and 1.5% of all samples studied. Peak
      incidence was found between December and March of the two years studied. Of the
      32 patients in whom hMPV was detected, 17 (53.2%) were female and 15 (46.8%)
      male. Mean age was 12.5 months (range, 1 month-4 years). The most frequent
      clinical symptoms were fever (90.6%), cough (87.5%), rhinorrhea and bronchiolitis
      (46.8%). Three patients (9.4%) were hospitalized. CONCLUSIONS: Respiratory
      infection caused by hMPV is considered an emergent disease in pediatric patients.
      The clinical manifestations are very similar to those of RSV infection; hence,
      only virological study can establish the definite etiological diagnosis.

PMID- 18341918
TI  - [Microbiological Surveillance Network in the Valencian community].
AB  - BACKGROUND: Computerization of microbiological laboratories generates an enormous
      amount of data that has not been fully exploited due to the heterogeneity of the
      information systems used. The aim of this paper is to present the Microbiological
      Surveillance Network of the Valencian Community, which provides real-time
      detection of circulating microorganisms and resistance patterns, and enables
      microbiological surveillance in the public health setting. METHODS AND RESULTS:
      We describe the Microbiological Surveillance Network of the Valencian Community,
      an information system that gathers, analyzes and disseminates the results of
      microbiological testing to health professionals in our setting. CONCLUSION:
      Development of the Microbiological Surveillance Network has made available a
      centralized system with the results from all the microbiological analyses
      performed in hospital laboratories of the Valencian Community. This effort
      provides valuable information for public health, and for studies in research and
      quality. In addition, it demonstrates the important role of microbiology within
      the field of medicine and public health.

PMID- 18341919
TI  - [Antifungal activity of posaconazole and caspofungin in yeast causing invasive
      fungal infection (2002-2003). E-test system evaluation].
AB  - Posaconazole (POS) and caspofungin (CAS) are new therapeutic options for treating
      fungal infection. This study establishes the activity of POS and CAS against
      yeast causing invasive fungal infections. In addition, the utility of the E-test
      system for estimating the minimum inhibitory concentrations (MICs) related to
      these antifungal drugs has been assessed. The study includes 53 yeast isolates
      causing invasive fungal infection. MIC50 and MIC90 values were determined by the
      M27-A2 reference method. MIC values obtained with the reference method were then
      compared with those obtained with E-testing. The results were MIC50/90
      (microg/mL) POS: 0.25/1, CAS: 0.06/4. Overall agreement with E-test: POS: 63.9%,
      CAS: 80.2%. None of the yeast isolates studied showed high MIC values for POS and
      CAS. Although it has some limitations, the E-test is a simple and fairly reliable
      system for determining the MICs of POS and CAS for yeast.

PMID- 18341920
TI  - [Human immunodeficiency virus-infected patients with community-acquired
      pneumonia: implication of respiratory viruses].
AB  - The role of respiratory viruses in community-acquired pneumonia (CAP) in human
      immunodeficiency virus (HIV)-infected patients has not been extensively
      investigated. The objective was to study the implication of respiratory viruses
      in HIV patients with CAP, through a prospective, three-year study in a third
      level hospital. Respiratory viruses were implicated in 14 of the 67 cases of CAP
      diagnosed and were the only microorganism isolated in 8 of them. Evolution of the
      disease was similar in patients with CAP associated with respiratory virus
      infection and those with CAP alone. Respiratory virus infection in HIV-infected
      patients with CAP is not associated with a poorer prognosis.

PMID- 18341921
TI  - Completely sequenced genomes of pathogenic bacteria: a review.
AB  - Six out of ten completely sequenced bacterial genomes are pathogenic or
      opportunistic bacteria. The genome sequence of at least one strain of all the
      principal pathogenic bacteria will soon be available. This information should
      enable us to identify genes that encode virulence factors. As these genes are
      potential targets for drugs and vaccines, their identification should have
      considerable repercussions on prevention, diagnosis, and treatment of the main
      bacterial infectious diseases. Comparison of genome sequences of several strains
      of the same species should allow identification of the genetic clues responsible
      for the differing behavior of related bacterial pathogens. This article reviews
      the genomes from pathogenic bacteria that have been or are currently being
      sequenced, describes the main tasks to be accomplished after a genome sequence
      becomes available, and discusses the benefits of having the genome sequence of
      bacterial pathogens.

PMID- 18341922
TI  - [Diagnosis, management and treatment of chronic Chagas' heart disease in areas
      where Trypanosoma cruzi infection is not endemic].
AB  - Chagas' disease, or American trypanosomiasis, is a parasitic zoonosis found only
      in the Americas. Under natural conditions, Trypanosoma cruzi is transmitted by
      insects belonging to different species of Triatoma. However, several routes of
      transmission that do not involve insect vectors have also been described, such as
      transmission via blood products or transplantation of infected organs, and
      vertical transmission. At present, the number of people infected with Chagas'
      disease worldwide is estimated to be about 10-12 million. The process of
      urbanization in Latin America and migratory population movements from endemic
      countries have led to the disease being diagnosed in non-endemic areas. It is
      estimated that 20-30% of individuals infected with T. cruzi will develop
      symptomatic heart disease at some point during their lives. The specific
      differential characteristics of chronic chagasic cardiopathy, lack of knowledge
      of the disease among many healthcare workers, and the fact that arrhythmia or
      sudden death is frequently the first manifestation of disease all make it
      essential that diagnostic and therapeutic protocols for the disease are developed
      and disseminated. The aim should be to improve patient care by increasing
      understanding of the condition by physicians and other healthcare professionals
      who may be involved in its detection and treatment.

PMID- 18341923
TI  - [Activity of antimicrobial agents on bacterial biofilms].
AB  - Bacterial biofilms are very resistant to antimicrobial activity. The
      concentration of drugs required to achieve bactericidal activity may be several
      orders of magnitude higher than the sensitivity for planktonic bacteria, since it
      is very difficult to completely sterilize infected surfaces. Biofilm
      antimicrobial resistance is a multifactorial process and is mainly related to the
      structural and physiological characteristics of the biofilms. Various control
      strategies have been designed to inhibit biofilm formation on medical devices, in
      most cases with little success. The most important mechanisms of biofilm
      resistance to antimicrobial agents and their effect on the activity of the main
      groups of antimicrobials are discussed.

PMID- 18341924
TI  - [Worsening of leprosy lesions in a Philippine-born patient].

PMID- 18341925
TI  - [A 34-year-old man with diarrhea and epigastralgia].

PMID- 18341926
TI  - [Greater hand hygiene adherence in hospitals is possible].

PMID- 18341927
TI  - [Diabetes mellitus during interferon therapy].

PMID- 18341929
TI  - [Assessment of commercial tuberculocidal products: normalization].

PMID- 18341930
TI  - [Introduction: update in cardiology].

PMID- 18341931
TI  - [Update on geriatric cardiology].
AB  - This article contains a review of the main developments in the field of geriatric
      cardiology reported during 2007, and discusses recent consensus statements. The
      article focuses on work dealing with the specific characteristics of elderly
      patients with ischemic heart disease, arrhythmias, heart failure, pulmonary
      hypertension and valvular heart disease.

PMID- 18341932
TI  - [Advances in pediatric cardiology and congenital heart diseases].
AB  - This article reviews the most significant developments reported between July 2006
      and July 2007 in the fields of pediatric cardiology and congenital heart disease,
      in diagnosis and treatment in particular. In the area of imaging techniques, the
      increasing clinical roles of magnetic resonance imaging, tissue Doppler imaging
      and three-dimensional echocardiography are highlighted, as is the application of
      these techniques to fetal cardiology and its repercussions. The incidence and
      treatment of arrhythmias in children are also discussed and, with regard to heart
      failure, there is an assessment of recent findings in epidemiology and diagnosis,
      new drugs, ventricular assist systems, and the current status of heart
      transplantation. In the area of interventional cardiology, present-day techniques
      for the closure of atrial and ventricular septal defects are reviewed and there
      is an assessment of early results with partially absorbable devices, percutaneous
      pulmonary valve implantation, and new types of stent (e.g., premounted, coated
      and absorbable stents). In cardiac surgery, the focus is on studies that evaluate
      outcome quality, the search for new biocompatible conduits, experience with new
      techniques for treating complex transpositions (e.g., the Nikaidoh procedure and
      its variants), the medium- and long-term results of treating aortic valvular
      disease with pulmonary autografts (i.e., the Ross and Ross-Konno procedures), and
      current findings on the treatment of pulmonary insufficiency after correction of
      either the tetralogy of Fallot or a dysfunctional Fontan circuit.

PMID- 18341933
TI  - [Arrhythmias and cardiac electrophysiology].
AB  - This article contains a review of some of the most significant advances in
      cardiac arrhythmias that have taken place in the last year, particularly those
      concerning the most common clinical conditions associated with the risk of
      arrhythmia, such as sudden cardiac death, atrial fibrillation and syncope, and
      genetically determined and hereditary heart disease, as well as advances
      concerning the principal nonpharmacologic treatments, such as catheter ablation,
      and the use of implantable defibrillators and cardiac resynchronization therapy.

PMID- 18341934
TI  - [Ischemic heart disease: update].
AB  - This article contains a review of the main developments reported during 2007 in
      either publications or presentations on patients with ST-segment elevation or non
      ST segment elevation acute coronary syndromes in the areas of pathophysiology,
      secondary prevention, prognosis and treatment. In addition, the latest clinical
      practice guidelines are discussed.

PMID- 18341935
TI  - [Heart failure].
AB  - This article discusses the most important developments in heart failure reported
      during the last year. It contains a review of new findings on chronic heart
      failure, acute heart failure, cardiac resynchronization therapy, heart
      transplantation, with particular emphasis on the situation in Spain, and surgery
      in heart failure. In addition, the article describes progress in the treatment of
      anemia, vasopressin receptor antagonists, non-invasive ventilation, inotropic
      therapy, and resynchronization therapy in patients with heart failure and atrial
      fibrillation, and examines the current role of echocardiography in detecting
      asynchrony and in selecting patients.

PMID- 18341936
TI  - [Advances in hypertension and diabetes in 2007].
AB  - This article contains a review of some of the main developments reported in 2007
      on the topics of hypertension and diabetes. The most important was the
      publication of the European Society of Cardiology's clinical practice guidelines
      on the two conditions, both of which have been adopted by the Spanish Society of
      Cardiology. Elsewhere, we have recently been witnessing crucial debates on the
      use of rosiglitazone for the treatment of diabetes and on the drug's effect on
      cardiovascular outcomes. The evidence available up to the present time is
      assessed. Finally, we will review the results of the most recent large clinical
      trial on the prevention of vascular complications in diabetics, which employed an
      antihypertensive approach.

PMID- 18341937
TI  - [Interventional cardiology].
AB  - Percutaneous intervention, both coronary and noncoronary, is one area of medicine
      that has experienced significant progress in recent years. This article does not
      attempt to present an exhaustive review of all the publications that have
      appeared in the field in the last year, but is rather intended to summarize those
      which have had the greatest impact on daily practice. The controversy about drug
      eluting stents (DESs) revived in the last year with the emergence of copious data
      that has, finally, demonstrated that DESs can reduce the need for
      revascularization at the expense of a slight increase in the rate of late stent
      thrombosis, though without a significant increase in mortality. Nonetheless, the
      patients who will benefit most must be carefully selected and double antiplatelet
      therapy must be continued for at least a year. The debate about the use of
      percutaneous coronary intervention (PCI) for unprotected left main coronary
      artery stenosis remains open while the results of randomized clinical trials
      comparing it with surgery are awaited. For the treatment of bifurcation lesions,
      it appears that implantation of a single stent, when possible, provides the
      optimum approach. The treatment of chronic total occlusions continues to provide
      a real challenge for PCI, though both the number treated and the success rate are
      increasing. The use of DESs and new antiplatelet drugs, which are safer but no
      less effective, is revolutionizing the treatment of non-ST-elevation acute
      coronary syndrome. Moreover, the role of primary PCI is increasingly being
      recognized in the treatment of acute myocardial infarction, as is the importance
      of reducing the door-to-balloon-angioplasty time. However, there are well-founded
      doubts about the safety of DESs in this setting. There has been a significant
      increase in the use of closure devices for closing patent foramen ovale in the
      past year, and there have been reports of possible benefits in patients with
      migraine.

PMID- 18341938
TI  - [Clinical cardiology: update].
AB  - Clinical cardiology encompasses all forms of heart disease and their more general
      characteristics, and its sphere of activity includes practical aspects of
      prevention, diagnosis, and inpatient and outpatient treatment as applied to
      patients on an everyday basis. Since certain areas of cardiology have become
      highly specialized, this review of new developments reported in the past year has
      attempted to bring together all those advances that are not the subject of
      research in some particular specialization within cardiology and that have such a
      wide range of application that they should be familiar to all clinical
      cardiologists, irrespective of their daily responsibilities. For the purposes of
      this review, articles were classified according to their origin as either English
      language, European, or domestic publications. The review concludes with a summary
      of registry data collected in the last two years by the Clinical and Outpatient
      Cardiology Section of the Spanish Society of Cardiology.

PMID- 18341939
TI  - [Cardiovascular prevention and cardiac rehabilitation].
AB  - This article contains a review of the main developments in cardiovascular disease
      prevention reported during the last year. In addition, the most recent clinical
      practice guidelines are also discussed. The aims of cardiovascular prevention are
      to reduce mortality and morbidity in individuals at a high risk and to help those
      at a low risk to maintain their status. Lifestyle modification and the reduction
      of modifiable cardiovascular risk factors are key to cardiovascular disease
      prevention. The implementation of clinical practice guidelines provides the
      primary means of achieving these goals.

PMID- 18341940
TI  - [Update on cardiac imaging techniques. Echocardiography, cardiac magnetic
      resonance and multidetector computed tomography].
AB  - This review of progress in cardiac imaging techniques summarizes the most
      significant development reported in the last year on different echocardiographic
      techniques and their application in a range of settings, from the treatment of
      heart failure to their use in intraoperative monitoring and guiding
      interventional procedures. Large sections are devoted to recent developments in
      three-dimensional imaging and, because of its clinical importance, to magnetic
      resonance imaging. Finally, there is a comprehensive update on the use of
      multidetector computed tomography in cardiology.

PMID- 18341941
TI  - [Progress in cardiac pacing].
AB  - This review summarizes recent scientific developments in ambulatory monitoring
      and its legal implications in appropriately selected patients. It also considers
      how new cardiac pacing devices can be used in the clinical monitoring of atrial
      fibrillation, sleep apnea and, in transplant patients, heart failure and
      transplant rejection. In addition, the system of accreditation for cardiac pacing
      services in Spain is outlined, with a focus on process development and quality
      indicators. Finally, the scientific articles on cardiac pacing that made the
      greatest impact in 2007 are summarized.

PMID- 18341942
TI  - Secondary aortoenteric fistula after endovascular aortic interventions: a
      systematic literature review.
AB  - PURPOSE: To evaluate the collective incidence of, and experience with,
      aortoenteric fistula after endovascular aortoiliac therapy. MATERIALS AND
      METHODS: A systematic literature research was performed to identify cases of
      aortoenteric fistulation after aortic stent-graft procedures or stent
      implantation. RESULTS: The review revealed 16 cases of aortoenteric fistulation
      after aortic stent-grafting (n = 15) or stent placement (n = 1), in 14 patients
      with abdominal aortic aneurysm. Six had undergone endovascular aneurysm repair
      because of what was considered a "hostile abdomen." The symptoms did not differ
      from those in patients with arterioenteric fistulation after open aortic repair.
      A defect in the stent-graft or its function was the predominant cause of
      fistulation. One fistula was diagnosed at autopsy, two patients died
      perioperatively, and 13 survived with in situ repair or an axillobifemoral graft,
      all after removal of the stent-graft or stent. However, the follow-up time was
      short, longer than 1 year in only five of the 13 survivors. CONCLUSIONS:
      Aortoenteric fistulation does occur after endovascular implantation of stents and
      stent-grafts. The incidence is unknown but is probably low. Follow-up time in
      most publications was less than 1 year, which is considered short to assess
      potential graft infection.

PMID- 18341943
TI  - Inadvertent C-arm movements: potential cause of patient and staff injury.

PMID- 18341944
TI  - Does percutaneous transluminal angioplasty improve quality of life?
AB  - PURPOSE: To prospectively assess the impact of peripheral percutaneous
      transluminal angioplasty (PTA) on quality of life (QOL) in patients with
      intermittent claudication or critical limb ischemia (CLI). The secondary purpose
      was to determine if periprocedural medication altered patient QOL. MATERIALS AND
      METHODS: A total of 72 patients underwent lower-limb PTA (86 lesions) over a
      period of 12 months. QOL data were obtained before PTA and at 1 and 6 months
      after PTA with use of the Short Form-36 (SF-36) questionnaire. RESULTS: The SF-36
      questionnaire was completed in 100% of cases before PTA, in 89% at 1 month after
      PTA, and in 78% at 6 months after PTA. Baseline QOL was worse than the QOL quoted
      for the normal population. Overall, there was an improvement in QOL in seven of
      the nine health domains at 1 month after PTA, and the improvements were
      significant (P < .01) in five. Improvement was demonstrated at 6 months in all
      nine QOL domains measured, which was significant (P < .01) in five. Patients with
      intermittent claudication (n = 40) exhibited an improvement in all nine health
      domains at 6 months, which was significant (P < .05) in seven. The CLI group (n =
      32) showed an improvement in five domains at 6 months, which was significant (P <
      .05) in two. Subjects with intermittent claudication experienced a more
      significant improvement than those with CLI. SF-36 pain scores at 1 month after
      PTA were significantly better in patients taking aspirin than in those who were
      not (P < .001). CONCLUSIONS: PTA results in improved QOL in patients with
      intermittent claudication and CLI as early as 1 month, which was shown to be
      maintained at 6 months in our small series. Aspirin significantly improves pain
      after PTA. QOL assessment is useful after peripheral angioplasty.

PMID- 18341945
TI  - How do patients perceive the benefits and risks of peripheral angioplasty?
      Implications for informed consent.
AB  - PURPOSE: To explore perceptions of benefits and risks of patients undergoing
      peripheral angioplasty and to investigate factors that modify them. MATERIALS AND
      METHODS: Two hundred patients undergoing peripheral angioplasty during a 12-month
      period (134 men and 66 women; mean age, 68.8 years; age range, 37-94 years) were
      interviewed by one interventional radiologist who asked 18 questions with regard
      to the risks and benefits of this procedure. The patients were randomly assigned
      into two groups of 100 patients. The first group answered questions with use of a
      recognized risk assessment chart. The other group answered without the aid.
      Depending on the referral pathway, patients received the institution's patient
      information sheet. RESULTS: Of the 200 patients, 178 (89%) thought that they
      would have at least a 75% (three in four) chance of benefiting from angioplasty.
      Eighty patients (40%) thought they would definitely benefit from angioplasty. One
      hundred one patients (50%) thought the test would be painful. Fifty-four patients
      (27%) thought there would be no radiation exposure. Forty-one patients (21%)
      realized there was a chance of needing emergency surgery. Sixty-seven patients
      (34%) thought the test was easier than anticipated. Previous peripheral
      angioplasty altered perceptions of benefit (P = .012), but not risk. The use of a
      risk assessment chart altered perceptions of benefit (P = .049). The use of a
      patient information sheet predicted (made more realistic) the patients'
      perceptions of risks (P = .012) and benefits (P = .001). CONCLUSIONS: Patients
      who undergo peripheral angiography tend to underestimate the risks and
      overestimate the benefits of peripheral angioplasty. The patient information
      sheet and risk assessment tool used in this study altered patient perceptions of
      risks and benefits of the procedure and, therefore, aid informed consent.

PMID- 18341946
TI  - Low-profile primary stent placement for the treatment of focal calcified
      ulcerated stenosis in the infrarenal aorta.
AB  - PURPOSE: To analyze the immediate and midterm success of low-profile stent
      placement in calcified ulcerated lesions of the infrarenal aorta in patients with
      arterial occlusive disease. MATERIALS AND METHODS: In this prospective case
      series, 13 symptomatic patients (eight men, five women; mean age, 64.8 years +/-
      12.1; age range, 44-84 years) with focal calcified ulcerated stenoses of the
      infrarenal aorta were treated with stent placement by using a low-profile
      technique in a radiology intervention center during a 4-year period. Clinical
      examinations and duplex ultrasonography were used to evaluate the stents? patency
      and clinical success. Kaplan-Meier graphs were calculated to analyze the freedom
      of-symptom rate. RESULTS: The initial technical success rate was 92% (12 of 13
      patients). Due to extended calcifications, a residual stenosis of 50%-60%
      remained in one patient. No peri-interventional complications occurred. The mean
      follow-up was 26 months (range, 5-53 months). During follow-up, one patient had a
      restenosis after 7 months and presented clinically with Fontaine stage IIb. Two
      patients had iliac and/or femoral stenoses, and both presented with Fontaine
      stage IIb. One patient's symptoms originated from the lumbar spine. Primary
      patency and primary clinical success rates were 85% and 69%, respectively.
      According to Kaplan-Meier tables, the freedom-from-symptom rates were 92%, 84%,
      73%, and 63% at 0, 7, 12, and 21 months, respectively. CONCLUSIONS: Low-profile
      stent placement in calcified, ulcerated lesions of the infrarenal aorta is an
      effective and safe treatment for symptomatic stenoses in patients with arterial
      occlusive disease after a mean follow-up of 26 months.

PMID- 18341947
TI  - Cholesterol embolism evaluated by polarized light microscopy after primary renal
      artery stent placement with filter protection.
AB  - PURPOSE: Cholesterol microembolization may explain some treatment failures after
      renal artery stent placement. The identification of cholesterol crystals may
      provide significant help in diagnosing the real frequency and severity of this
      complication. The aim of the present study was to examine the efficacy of
      polarized light imaging in the detection of cholesterol emboli trapped in a
      protection device. MATERIALS AND METHODS: During a period of 18 months, 15
      significant atherosclerotic stenoses of the ostium of the main renal artery were
      treated with primary stent placement with embolic protection. The filter device
      used was made of polyurethane, with a pore size of 115 ?m. The device was mounted
      over a 0.014-inch guide wire. For pathologic analysis, the recaptured filter
      basket was compressed between two slides and examined in a microscope under
      polarized light. RESULTS: All the stenoses were successfully treated without
      clinical complications. All the filters were deployed and recaptured without
      difficulty. Cholesterol crystals were detected in 12 filters and no cholesterol
      was found in three. In one case, trouble with filter manipulation precluded
      pathologic analysis. No worsening of renal function was detected in any patient
      during follow-up. CONCLUSIONS: Microscopic analysis with polarized light easily
      detects the cholesterol crystals trapped in the filter device. This provides
      evidence that renal cholesterol microembolism is highly prevalent during renal
      artery stent placement.

PMID- 18341948
TI  - Long-term efficacy and safety of uterine artery embolization in young patients
      with and without uteroovarian anastomoses.
AB  - PURPOSE: To assess long-term clinical efficacy of uterine artery embolization
      (UAE) in young women and the clinical significance of patent anastomoses between
      uterine and ovarian arteries. MATERIALS AND METHODS: Consecutive women no older
      than 39 years of age treated with UAE for symptomatic uterine leiomyomata with at
      least 3 years of follow-up were included in the study. Analysis includes
      angiographic images, pre- and postoperative magnetic resonance (MR) images, and
      symptom evaluations. Clinical evaluation and symptom severity scores (SSSs) were
      obtained at 6 months and yearly. Leiomyomata volume change, SSS, and repeat
      intervention rates were compared for patients with and without anastomoses
      between uterine and ovarian arteries. RESULTS: The study cohort included 87
      patients, including 30 white patients (34.4%), 49 black patients (56.3%), and
      eight patients of other ethnicities (9.2%). Anastomoses were demonstrated in 41
      patients (47.1%). Seventy patients (80.5%) completed the long-term follow-up, of
      whom 35 had an anastomosis (85.4% of the 41 patients with anastomoses) and 35 did
      not (76.1% of the 46 patients without anastomoses). Mean leiomyoma volume
      reduction was 49.1% (P = .018), and reduction of uterine volume was 36.0% (P <
      .001). Mean clinical follow-up duration was 45 months. Overall, 18 of 70 patients
      (25.7%) underwent repeat interventions, including 13 (37.1%) with anastomoses and
      five (14.3%) without anastomoses (P = .029). One patient (1.4%) developed natural
      amenorrheic change in the long term after UAE. Nineteen patients (27.1%)
      attempted pregnancy after UAE, and 12 patients had 15 pregnancies, with six
      pregnancies to full term. CONCLUSIONS: UAE in young patients achieves significant
      dominant leiomyoma volume reduction and symptomatic improvements, with overall
      repeat intervention rates of 25.7% in the long term. Uteroovarian anastomoses in
      young patients are associated with higher rates of repeat intervention after UAE.

PMID- 18341949
TI  - Tunneled infusion catheter breakage: frequency and repair kit outcomes.
AB  - PURPOSE: To determine the frequency of tunneled infusion catheter breakage and
      the durability of a repair kit used to repair damage to the external catheter
      segment, avoiding catheter replacement. MATERIALS AND METHODS: With use of a
      quality assurance database, 724 silicone tunneled infusion catheters placed
      between July 2002 and September 2005 were identified. The repair kit outcomes
      portion of the study focused on 10-F triple-lumen catheters (n = 433), the type
      placed most frequently in our practice and that with the most repairs available
      for analysis. To compare durability, nonrepaired catheters and those requiring
      repair were compared by using Cox proportion hazard regression. RESULTS: Breakage
      occurred in 53 of 443 (12%) 10-F triple-lumen catheters, three of 64 (5%) 10-F
      dual-lumen catheters, four of 159 (3%) 11-F triple-lumen catheters, four of 12
      (33%) 9.6-F single-lumen catheters, and eight of 56 (14%) 9-F double-lumen
      catheters. In the 10-F subset, the mean time to catheter breakage was 60 days.
      The mean catheter days for the nonrepaired group (143 days) and the repaired
      group (145 days) were not significantly different (chi2, 0.071; hazard ratio,
      1.07; P = .79). Mean catheter dwell after repair was 79 days. The failure rate
      for the repair kit was 14% (seven of 51 attempts). CONCLUSIONS: Tunneled infusion
      catheter breakage is common. Given the high breakage rates observed for many
      catheter designs, the development of more durable catheters should be a priority
      for catheter manufacturers. Until more durable catheters are developed, the
      catheter repair kit studied is an easy, effective, durable, and relatively
      inexpensive solution for the repair of external segment damage in tunneled
      infusion catheters.

PMID- 18341950
TI  - Initial experience with 3% sodium tetradecyl sulfate foam and fibered coils for
      management of adolescent varicocele.
AB  - PURPOSE: To report the results of treatment of adolescent patients with
      varicocele with use of 3% sodium tetradecyl sulfate foam (STS) in combination
      with pushable fibered coils. MATERIALS AND METHODS: From September 2004 to
      September 2006, 16 adolescent patients (age 12-19 y) with symptomatic varicocele,
      testicular atrophy, or surgical recurrence underwent embolization with STS foam
      and coils. The left internal spermatic vein (ISV) was coaxially catheterized from
      the right femoral vein. Three percent STS foam was placed distally in the ISV
      during compression so minimal foam entered the pampiniform plexus. A second nest
      of coils was placed in the ISV at a position over the sacroiliac (SI) joint that
      occluded most of the parallel collateral vessels. Coils were not placed above the
      SI joint in most instances. Additional foam was injected in the ISV at the upper
      level of the SI joint. The upper ISV was left unoccluded. Our standard follow-up
      consisting of ultrasound and/or physical examination after varicocele occlusion
      was performed 2-12 months after the procedure. RESULTS: All occlusions were
      technically successful, and 15 of 16 patients (94%) exhibited proven
      disappearance of the varicocele. All patients were asymptomatic except one who
      had pain despite disappearance of the varicocele. One patient with a bleeding
      disorder had 48 hours of scrotal discomfort as a result of pampiniform phlebitis
      caused by the deliberate passage of foam into the pampiniform plexus.
      CONCLUSIONS: The use of 3% STS foam in combination with pushable fibered coils is
      a safe and effective sclerosing procedure for adolescent subjects with
      varicocele.

PMID- 18341951
TI  - Endovenous laser ablation of the saphenous veins: bilateral versus unilateral
      single-session procedures.
AB  - PURPOSE: To assess the feasibility of bilateral endovenous laser ablation (EVLA)
      of saphenous veins in a single session with use of diluted lidocaine for
      tumescent anesthesia. MATERIALS AND METHODS: Among 122 consecutive EVLA
      procedures (112 patients; mean age, 49 years; 75% women) over a 12-month period,
      there were 75 unilateral procedures (n = 67) and 47 bilateral interventions (n =
      45). Tumescent anesthesia consisted of lidocaine diluted to 0.10% for unilateral
      procedures versus 0.05% for bilateral cases (lidocaine dose <4.5 mg/kg body
      weight). Procedural data, immediate success rates on an intent-to-treat basis,
      and outcomes at 3-6-month follow-up were compared between groups with
      nonparametric tests. RESULTS: Bilateral procedures could be performed
      successfully with low lidocaine dilutions with a similar success rate (96%) as
      unilateral procedures (100%). No significant variation in systolic and diastolic
      blood pressure and heart rate was observed between bilateral and unilateral
      groups. No patient experienced signs of lidocaine toxicity. After adjusting for
      length of vein treated, there were no significant differences in the total
      lidocaine dose used, tumescent anesthesia volume, or procedure duration.
      CONCLUSIONS: Bilateral saphenous vein ablation in a single session appears safe
      and effective when tumescent anesthesia is given with very dilute lidocaine
      (0.05%). This approach may help meet patients' requests for simultaneous
      bilateral treatment and reduce duration of postprocedural discomfort.

PMID- 18341952
TI  - Role of biliary stress manometry after biliary stricture dilation in living donor
      liver transplant recipients.
AB  - PURPOSE: To report on the use of biliary manometry for determining treatment
      completion in living donor liver transplant recipients. MATERIALS AND METHODS:
      Twenty of 85 patients (24%) who underwent living donor liver transplantation
      developed postoperative anastomotic biliary strictures. Fifteen patients
      underwent transhepatic biliary drainage and percutaneous dilation. In 10
      patients, biliary stress manometry was used to assess treatment adequacy after a
      mean of 2.5 dilation sessions occurring during a mean period of 62 days (range, 5
      55 days). An intrabiliary pressure of less than 20-cm H2O after an escalating
      intrabiliary infusion to 1,200 mL per hour for 3 minutes was defined as the
      success threshold (in lieu of a capped external catheter "clinical trial").
      RESULTS: There were no complications during the infusion study. In all 10
      patients in whom manometry was successful, biliary catheters were removed. One
      patient (who underwent manometry and catheter removal after only one dilation
      session) required repeat intubation 7 weeks later. The remaining nine patients
      (90%) remained free of evidence of biliary obstruction at a mean of 8.4 months.
      With Kaplan-Meier survival analysis, the probability of biliary patency at 3, 6,
      and 12 months was 90%. CONCLUSIONS: This biliary stress manometry protocol offers
      a promising alternative to the catheter "clinical trial" for determining
      endpoints for multisession anastomotic biliary stricture dilation in living donor
      transplant recipients.

PMID- 18341953
TI  - Membrane degradation of covered stents in the upper gastrointestinal tract:
      frequency and clinical significance.
AB  - PURPOSE: To evaluate the frequency, clinical significance, and predictive factors
      of membrane degradation of covered stents in the upper gastrointestinal (UGI)
      tract. MATERIALS AND METHODS: From 1996 to 2006, 166 stents were removed from 151
      patients. Indications for stent removal included temporary stent placement for
      esophageal cancer before radiation therapy or radiation-chemotherapy (n = 53),
      stent migration (n = 40), temporary stent placement for a benign UGI stricture (n
      = 32), pain (n = 21), recurrent obstruction (n = 16), incomplete stent expansion
      (n = 1), recurrent transesophageal fistula (n = 2), and aspiration (n = 1).
      Removed stents were examined to evaluate possible causes of membrane degradation.
      Multivariate analysis was performed to determine the predictive factors of
      membrane degradation. RESULTS: Degradation of the covering membrane occurred in
      14 of the 166 stents (8%). Recurrent obstruction due to tumor ingrowth (n = 7)
      and reopening of the transesophageal fistula (n = 1) through the degraded
      membrane occurred in eight stents (5%). At multivariate logistic regression
      analysis, the type of covering membrane (P = .018), stricture location (P =
      .006), and duration of stent placement (P = .002) were significantly associated
      with degradation of the covering membrane. CONCLUSIONS: Degradation of the
      covering membrane after stent placement in the UGI tract is not an uncommon
      event, and recurrent obstruction or fistula can occur through the degraded
      membrane. A polyurethane membrane is not biostable and dissolves over time,
      particularly in the gastroduodenal area.

PMID- 18341954
TI  - New vertebral osteoporotic compression fractures after percutaneous
      vertebroplasty: retrospective analysis of risk factors.
AB  - PURPOSE: To investigate risk factors for new vertebral compression fractures
      (VCFs) after vertebroplasty. MATERIALS AND METHODS: The authors analyzed the
      occurrence of new VCFs in 70 patients who had previously undergone vertebroplasty
      for the treatment of one VCF. The following covariates were analyzed: age, sex,
      body weight, height, body mass index (BMI), treated vertebral level, relative
      distance between treated vertebrae and new VCFs, pre-existing untreated VCFs, gas
      containing vertebrae before treatment, and surgical approach. Surgical variables,
      including cement leakage into the disk, anterior vertebral height restoration,
      and kyphosis correction of treated vertebrae were also analyzed. A Cox
      proportional hazards regression analysis was used to determine the relative risk
      of new adjacent VCFs. The Kaplan-Meier method was used to calculate mean fracture
      free rate over time. RESULTS: Seventy patients were reviewed, with a mean follow
      up of 20.0 months +/- 10.2 (range, 6-48 months). We identified 22 new fractures
      in 19 of the 70 patients (27%), with 16 adjacent and six nonadjacent VCFs. The
      mean time to new fracture was 10.6 months +/- 9.5, and there was no significant
      difference in time to adjacent or nonadjacent VCF. Increased risk of VCF was
      associated with proximity to the treated vertebra, greater kyphosis correction,
      and low patient BMI. The 1-year fracture-free rate was 79.5%. CONCLUSIONS: New
      VCFs are common in patients with a low BMI, which suggests osteoporosis as a
      mechanism of fracture.

PMID- 18341955
TI  - Endovascular training with animals versus virtual reality systems: an economic
      analysis.
AB  - PURPOSE: To assess the relative costs of a virtual reality (VR) laboratory and an
      animal laboratory for endovascular skills training. MATERIALS AND METHODS: Cost
      data extracted from a previous experiment was used to perform a financial
      analysis according to the guidelines published by the National Institutes of
      Health. The analysis compared the purchase or rental of a Procedicus Vascular
      Interventional System Trainer to the rental of an animal laboratory. RESULTS: The
      VR laboratory course cost $3,434 per trainee versus $4,634 in the animal
      laboratory according to the purchase-versus-rental analysis. The cost ratio was
      0.74 in favor of the VR laboratory. Cost ratio sensitivity analysis ranged from
      0.25 in favor of the VR laboratory to 2.22 in favor of the animal laboratory. The
      first-year potential savings were $62,410 assuming exclusive use of the VR
      laboratory. The 5-year training savings totaled $390,376, excluding the $60,000
      residual value of the simulator. Simulator rental reduced the course price to
      $1,076 per trainee and lowered the cost ratio to 0.23 in favor of the VR
      laboratory. Findings of sensitivity analysis ranged from 0.08 to 0.70 in favor of
      the VR laboratory. The first-year and 5-year potential national savings increased
      to $185,026 and $1,013,238, respectively. CONCLUSIONS: Although evidence remains
      sparse that the training of interventional skills in artificial environments
      translates to better performance in human procedures, there are good pedagogic
      grounds on which to believe that such training will become increasingly
      important. The present comparison of the direct costs of two such models suggests
      that VR training is less expensive than live animal training.

PMID- 18341956
TI  - Pancreas allografts: comparison of three-dimensional rotational angiography with
      standard digital subtraction angiography.
AB  - PURPOSE: To define the role of three-dimensional (3D) rotational angiography (RA)
      for the evaluation of pancreas allografts and compare 3D RA to standard digital
      subtraction angiography (DSA). MATERIALS AND METHODS: DSA and 3D RA were
      performed in patients with vascular abnormalities diagnosed on contrast medium
      enhanced magnetic resonance (MR) angiography. Patency of the allograft
      vasculature, confidence in the ability to make a therapeutic decision, and value
      of the study for definition of the optimal projection for an intervention was
      assessed on a graded scale. RESULTS: Seventeen standard DSA projections (mean,
      3.4; range, 2-6) and 10 3D RA images (mean, 2; range, 1-3) were obtained in five
      patients. An average iodinated contrast agent dose of 14.4 mL (range, 8-22 mL)
      was administered for DSA. An average CO2 dose of 54 mL (range, 0-120 mL) was
      administered for 3D RA. Five 3D RA procedures were timed for the arterial phase
      and five were timed for the arterial and venous phases. Average contrast agent
      doses were 17.6 mL (range, 11-22 mL) for arterial 3D RA and 24.4 mL (range, 16-34
      mL) for arterial- and venous-phase 3D RA. Of 68 vascular segments available for
      direct comparison of patency, complete concordance was present in 96%. There was
      no difference in the reviewers' diagnostic confidence (10 +/- 0 for both
      techniques). Three-dimensional RA was considered significantly superior for
      planning the optimal projection for intervention (10 +/- 0 for 3D RA vs 7.2 +/-
      1.6 for DSA; P = .0052). CONCLUSIONS: Three-dimensional RA of pancreatic
      allografts is feasible and does not differ in accuracy from conventional DSA. It
      provides similar reviewer confidence in the ability to make an accurate treatment
      decision, but its key advantage is its superior ability to define the optimal
      projection for planned endovascular interventions.

PMID- 18341957
TI  - Similarity of the swine vasculature to the human carotid bifurcation: analysis of
      arterial diameters.
AB  - PURPOSE: We assessed the similarities of the iliac bifurcation in two breeds of
      swine to the known human carotid bifurcation, in order to assess its
      applicability as a preclinical model of the human carotid bifurcation. MATERIALS
      AND METHODS: Mixed-Landrace crossbreed (domestic; n = 66) and Yucatan miniswine
      (Yucatan; n = 13) were studied. The diameters of the iliac bifurcation arteries
      were measured from angiographic pictures, the relations between the arterial
      diameters and the animal's weight assessed, and diametrical ratios calculated.
      Findings were compared with the known human carotid bifurcation. RESULTS: The
      external iliac diameter (approximately 6-7mm) in the lower weight swine was
      similar to the known human common carotid artery. The best similarity was found
      between the diametrical ratios of the human internal to common carotid artery
      (mean 0.63) to the swine profunda to external iliac (means 0.68 and 0.65 for the
      domestic and Yucatan, respectively). The arterial diameters of the domestic swine
      were highly correlated with their weight that increased considerably with time,
      while in the Yucatan group, arterial diameters did not change with increasing
      weight and the average weight increase rate was low. Thus, the estimated arterial
      diameter increase rate over time was high in the domestic while minor in the
      Yucatan group. CONCLUSIONS: Similarities were found between the swine iliac
      bifurcation arteries to the human carotid bifurcation in terms of diameters,
      diametrical ratios and angle. The swine iliac bifurcation may be used for
      preclinical endovascular research of devices intended to the human carotid
      bifurcation, with miniswine strains a preferable model for long-term studies.

PMID- 18341958
TI  - Expression of hypoxia inducible factor-1 alpha, macrophage migration inhibition
      factor, matrix metalloproteinase-2 and -9, and their inhibitors in hemodialysis
      grafts and arteriovenous fistulas.
AB  - PURPOSE: It is well recognized that arteriovenous fistulas (AVFs) used for
      hemodialysis access have better primary patency rates with less restenosis than
      polytetrafluoroethylene (PTFE) grafts; however, the mechanism responsible for
      this is not known. Recent data suggest that hypoxia inducible factor-1 alpha (HIF
      1 alpha) is associated with vascular restenosis, possibly through mechanisms that
      increase the production of macrophage migration inhibition factor (MIF), matrix
      metalloproteinase-2 (MMP-2) and MMP-9, and their inhibitors (tissue inhibitor of
      MMPs; TIMP). The present study tested the hypothesis that there are differences
      in the expression patterns of HIF-1 alpha, MIF, MMP-2, MMP-9, and TIMPs in
      specimens removed from patients with AVFs and PTFE grafts. MATERIALS AND METHODS:
      Whole-vessel tissue samples were obtained from the vein distal to the vein-to
      PTFE graft anastomosis and the proximal outflow vein (within 6 cm of the
      arteriovenous anastomosis) of AVFs from 17 patients who required a surgical
      revision for thrombosis and stenosis. Nonstenotic veins of four patients
      undergoing hemodialysis vascular access placement were used as controls. PTFE
      grafts (n = 6), AVFs (n = 6), and control samples (n = 3) underwent Western blot
      analysis and zymography. A separate group of five patients with PTFE hemodialysis
      grafts and one control subject were used for immunohistochemical analysis.
      RESULTS: Specimens from patients with PTFE grafts had significantly higher
      expression of HIF-1 alpha (P = .03), MIF (P = .02), TIMP-1 (P = .0006), pro-MMP-2
      (P = .02), and pro-MMP-9 (P = .046) compared with control veins. The expression
      of only pro-MMP-9 was significantly higher in AVFs compared with control samples
      (P = .004). There was a significant increase in the expression of MIF (P = .007)
      and TIMP-1 (P < .0001) in PTFE graft specimens compared with AVFs. MIF and TIMP-1
      were localized to the adventitia of the vein distal to the vein-to-PTFE graft
      anastomosis. CONCLUSIONS: There were major differences in the expression patterns
      of hypoxia (ie, HIF-1 alpha) and proteins regulated by HIF-1?, including MIF, pro
      MMP-2, pro-MMP-9, and TIMP-1, in specimens removed from patients with PTFE grafts
      and AVFs. Understanding the role of HIF-1 alpha and these proteins in
      hemodialysis access failure can help improve outcomes.

PMID- 18341959
TI  - Increased expression of hypoxia-inducible factor-1 alpha in venous stenosis of
      arteriovenous polytetrafluoroethylene grafts in a chronic renal insufficiency
      porcine model.
AB  - PURPOSE: To create a more clinically relevant model of hemodialysis graft failure
      in pigs by creating chronic renal insufficiency before polytetrafluoroethylene
      (PTFE) hemodialysis graft placement and to determine the expression of hypoxia
      inducible factor-1 alpha (HIF-1 alpha) at the vein-to-graft anastomosis (VGA).
      MATERIALS AND METHODS: Chronic renal insufficiency was created in 14 castrated
      juvenile male pigs with complete embolization of the left renal artery and the
      partial embolization of the right renal artery by infusing 150-250-mum polyvinyl
      acrylide spherical particles. The efficacy of the embolization was assessed by
      determining the amount of polyvinyl acrylide particles used per kidney, the
      weight of the kidneys at sacrifice, and kidney function (blood urea nitrogen
      [BUN] and creatinine levels). Twenty-eight days after embolization, PTFE grafts
      were placed from the carotid artery to the ipsilateral jugular vein and removed
      3, 7, and 14 days after graft placement. Western blot for HIF-1 alpha was
      performed in the VGA and control vessel. RESULTS: The left kidney required two
      times the polyvinyl acrylide particles than did the right kidney (P < .05). The
      right kidney weighed nearly three times more than the left (P < .05). The BUN and
      creatinine levels at graft placement were significantly higher than those at
      baseline (P < .05). Four grafts were patent at day 3, four at day 7, and four at
      day 14. By day 7, the mean HIF-1 alpha at the VGA had increased significantly
      when compared with that of control vessels (P < .05). CONCLUSIONS: A more
      clinically relevant porcine model of hemodialysis graft failure was created, and
      there was significantly increased expression of HIF-1 alpha by day 7 at the VGA.

PMID- 18341960
TI  - Transcatheter arterial embolization with absolute ethanol injection for enlarged
      polycystic kidneys after failed metallic coil embolization.
AB  - Kidney enlargement in autosomal-dominant polycystic kidney disease (ADPKD) may
      cause symptoms by compressing the alimentary tract, lungs, and heart. The
      clinical symptoms may be progressive, may markedly decrease quality of life, and
      may even be life-threatening. Although treatment of this disease is often
      difficult, transcatheter arterial embolization (TAE) with metallic coils has been
      reported as a renal contraction therapy that is less invasive than surgery. The
      present report describes a case of ADPKD successfully treated by TAE with
      absolute ethanol after a previous TAE procedure with metallic coils failed to
      contract the affected kidneys because of recanalization.

PMID- 18341961
TI  - Treatment of complex stenoses involving renal artery bifurcations with use of
      drug-eluting stents.
AB  - Percutaneous angioplasty with stent placement is effective for the treatment of
      renal artery stenosis (RAS). RAS involving the bifurcation is technically
      challenging because of possible occlusion of a renal artery branch after stent
      implantation. The present report describes experiences in four patients with
      stenosis involving the renal artery bifurcation treated with drug-eluting stents
      (DESs). DESs were used instead of bare stents because of their potential
      advantage of lower restenosis rates. There was no evidence of restenosis on
      ultrasonography, with stable renal function and blood pressure at a median follow
      up of 13 months.

PMID- 18341962
TI  - Uterine artery embolization in patients with symptomatic diffuse leiomyomatosis
      of the uterus.
AB  - Six patients with symptomatic diffuse uterine leiomyomatosis underwent
      technically successful uterine artery embolization. After a median follow-up of
      16 months, five women presented with permanent alleviation of symptoms and a
      normalized quality of life according to the Uterine Fibroid Symptom and Quality
      of Life questionnaire. Magnetic resonance imaging showed impressive recovery of
      the myometrium, and the infarcted leiomyomas shrank and were partially expelled.
      No additional treatment was necessary. Failure of therapy occurred in one patient
      with atypical growth of fibroid tumor tissue shortly after embolization, which
      was suspicious for malignancy. Hysterectomy was performed and pathologic
      evaluation revealed benign leiomyomatosis.

PMID- 18341963
TI  - Retrograde cannulation of the thoracic duct and embolization of the cisterna
      chyli in the treatment of chylous ascites.
AB  - The authors offer a previously undescribed technique for cisterna chyli
      embolization in the treatment of chylous ascites. After the failure of
      conventional percutaneous direct cisterna chyli cannulation, the authors accessed
      the thoracic duct directly from the subclavian vein. Retrograde microcatheter
      access through the thoracic duct enabled embolization of the cisterna chyli.
      Embolization materials included fibered endovascular coils, gelatin sponge, and
      doxycycline. The patient's symptoms returned 10 days after embolization. This
      technique provided short-term success in the treatment of the patient's chylous
      ascites.

PMID- 18341964
TI  - CT fluoroscopy-guided postmyelographic transthecal radiofrequency ablation of a
      posterior vertebral body osteoid osteoma.
AB  - The present case report describes a unique case of radiofrequency (RF) ablation
      of an osteoid osteoma in the inferoposterior paramedian region of the L5
      vertebral body. After computed tomographic (CT) myelography, CT fluoroscopy was
      used to guide the transthecal approach of the RF ablation procedure.

PMID- 18341965
TI  - Laser ablation of a biliary duct for treatment of a persistent biliary-cutaneous
      fistula.
AB  - A persistent biliary-cutaneous fistula detected after biliary drainage catheter
      removal could not be resolved with diversionary techniques and Gelfoam and fibrin
      glue administration in the fistulous tract. As an alternative approach for
      treatment of the fistula, obliteration of the contributing bile duct with laser
      ablation was performed.

PMID- 18341966
TI  - Comment on "Fracture of a Nitinol Carotid Artery Stent that Caused Restenosis".

PMID- 18341967
TI  - Yttrium-90-labeled microsphere radioembolotherapy of liver-dominant metastases
      from thoracic malignancies.

PMID- 18341968
TI  - Embolization of a right gastroepiploic artery pseudoaneurysm associated with
      Churg-Strauss syndrome.

PMID- 18341969
TI  - [Targeted HCC therapies: the door has been opened!].

PMID- 18341970
TI  - [Use of sorafenib (Nexavar) in the treatment of hepatocellular carcinoma: PRODIGE
      AFEF recommendations].

PMID- 18341971
TI  - [Natural Orifice Translumenal Endoscopic Surgery: first procedures in humans and
      development strategy].

PMID- 18341972
TI  - Endoscopic resection of a large Brunner's gland hamartoma.
AB  - Brunner's Gland Hamartoma (BGH) is a benign tumor of the duodenum that can lead
      to gastrointestinal bleeding and intestinal obstruction. Endoscopic resection has
      seldom been reported. We describe the case of a duodenal obstruction caused by a
      large BGH (6 cm x 4 cm). We report a 57-year-old woman hospitalized for tarry
      stools, weight loss and anorexia. Endoscopy revealed a large BGH (6 cm x 4 cm).
      Endoscopic ultrasound (EUS) revealed a submucosal duodenal tumor. In this paper,
      we report a case of large hyperplasia of BGH, successfully treated by endoscopic
      technique.

PMID- 18341973
TI  - [Hormone replacement therapy and colorectal cancer].

PMID- 18341974
TI  - [National study of adjuvant treatments of resected cholangiocarcinoma].

PMID- 18341975
TI  - Multimodal imaging for the detection and characterization of liver lesions in a
      mouse model of neuroendocrine tumor.
AB  - BACKGROUND: The aim of this study was to compare in vivo magnetic resonance
      imaging (MRI) and ex vivo autoradiography with histopathological results for the
      detection and characterization of liver lesions in an experimental model of human
      neuroendocrine tumors. MATERIAL AND METHODS: Intestinal STC-1 endocrine tumor
      cells were injected into 30 nude mice to achieve hepatic dissemination. Seven to
      30 days after injection, T2-weighted in vivo images covering the entire liver
      were acquired with a 7-T system. Autoradiographs were also obtained in 28 mice
      after injection of fluorodeoxyglucose (18F-FDG). The autoradiographic liver
      samples were then stained with an antichromogranin antibody before histological
      analysis. Tumor size and the hepatic tumor fraction were measured using the three
      imaging modalities. RESULTS: Metastatic tumors visualized on the histological
      liver sections ranged in size from 50 microm (day 7) to 3 mm (day 30). The
      hepatic tumor fraction increased with time, reaching 30% of the hepatic surface
      area on day 30. Visual analysis revealed variable tumor distribution and type
      (solid and/or cystic). On MRI, lesions were identified from day 12 (about 100
      icrom in diameter) and the hepatic tumor fraction was up to 48% at day 30. The
      smallest lesions (350 microm in diameter) were also detected at day 12 on the
      autoradiographs. There was good correlation between tumor fractions determined
      from autoradiographic and histological data. CONCLUSION: In vivo, MRI appears to
      be well suited to the follow-up of liver lesions in a mouse model of
      neuroendocrine tumor. Preliminary results using 18F-FDG in this animal model are
      promising, showing differences in FDG uptake.

PMID- 18341976
TI  - [Chronic intestinal pseudo-obstruction and anti-Hu syndrome: 13 years of follow
      up without neoplasia].
AB  - Chronic intestinal pseudo-obstruction (CIPO) is a heterogeneous group of rare
      disorders characterised by symptoms of intestinal obstruction with no mechanical
      evidence of obstruction. It is caused by ineffective intestinal contractions due
      to visceral neuropathy and/or neuropathy. In adults, CIPO is mostly secondary.
      The most common causes are metabolic disorders, connective tissue disorders,
      neuropathic drug related injuries, paraneoplasic and post-infectious syndromes
      and amyloidosis. Secondary forms of CIPO have been reported with anti-Hu
      antibodies. This corresponds to an antineuronal antibody that recognizes a
      protein expressed in the nuclei of neuron (ANNA-1) and neoplasic cells. The anti
      Hu antibody must be searched for in patients over 40 years old with CIPO
      (associated with small cell lung cancer in 75% of cases). Recently, the
      association of CIPO and the anti-Hu antibody has been described without
      associated neoplasia. We report a case of an association of CIPO and anti-Hu
      antibody without cancer after 13 years of follow-up.

PMID- 18341977
TI  - [Long-term evolution of achalasia of the lower esophageal sphincter and
      intestinal paraneoplasic pseudo-obstruction revealing small cell lung carcinoma].
AB  - We report a case of a small cell carcinoma of the lung revealed by chronic
      intestinal pseudo-obstruction associated with achalasia of the lower esophageal
      sphincter. Tumoral remission was achieved for more than 21 months after
      chemoradiotherapy but this did not prevent the paraneoplasic syndrome from
      persisting and medical treatment was not successful in treating the intestinal
      pseudo-obstruction or the dysphagia, which was not improved by esophageal
      dilation.

PMID- 18341978
TI  - Hepatitis C virus structural proteins do not prevent human dendritic cell
      maturation.
AB  - AIM: Infection with hepatitis C virus (HCV) results in chronic hepatitis in more
      than 70% of cases. Alterations in the maturation of dendritic cells (DC) might
      play a role in the immune system's inability to eliminate the virus, although
      viral factors that could be involved have not been identified. This study in
      vitro investigated whether HCV structural proteins affect maturation of monocyte
      derived DC. METHODS: HCV proteins (core, E1, E2) were expressed by transduction
      with recombinant adenoviruses of immature DC. The ability of these transduced DC
      to respond to a maturation stimulus was evaluated by measuring cell surface
      markers, allogenic lymphocyte stimulation and interleukin (IL)-12 production.
      RESULTS: Expression of HCV structural proteins did not modify DC maturation in
      the presence of lipopolysaccharide, as determined by their phenotype and
      stimulatory functioning. IL-12 secretion was not affected by HCV protein
      expression in mature DC. CONCLUSION: Our results suggest that HCV structural
      proteins do not affect maturation of monocyte-derived DC by lipopolysaccharide.
      These findings are important for further studies to clarify the pathogenesis of
      chronic HCV infection and towards the rational design of cellular vaccine
      approaches for immunotherapy against hepatitis C.

PMID- 18341979
TI  - [Hepatic splenosis: a rare etiology of hepatic nodules].
AB  - Splenosis is the autotransplantation of splenic tissue, generally after traumatic
      splenic rupture. Usually, the peritoneal surface is affected. The viscera are
      rarely involved in this graft. We report a case of intrahepatic splenosis, which
      presented as a liver tumour on imagery in a 55-year-old man followed for lung
      carcinoma and chronic hepatitis C and who had undergone a splenectomy for trauma
      22 years before. The different characteristics and diagnostic methods of 16 cases
      of hepatic splenosis are presented from the literature. These different reports
      emphasize the necessity of considering splenosis in the differential diagnosis of
      hepatic tumours.

PMID- 18341980
TI  - [Idiopathic peliosis hepatis complicated by a hepatopulmonary syndrome].

PMID- 18341981
TI  - [The role of echoendoscopic biopsy in diagnosing tuberculosis of pancreas].
AB  - The diagnosis of an abdominal mass using imaging techniques is difficult for
      clinicians and radiologists. We report a case of an atypical peripancreatic mass,
      mimicking a carcinoma on abdominal computed tomography and which was only
      diagnosed after an echoendoscopic biopsy of the mass was performed. It is
      difficult to differentiate abdominal tuberculosis from a neoplasm, especially if
      there is no pulmonary tuberculosis. Usually, the diagnosis of abdominal
      tuberculosis is only confirmed histologically, after surgical resection of the
      mass. Echoendoscopic biopsy confirmed the infectious nature of the mass and
      prevented complicated and difficult surgery.

PMID- 18341982
TI  - V1 neurons: in tune with the neighbors.
AB  - In this issue of Neuron, Nauhaus et al. use a combination of optical imaging and
      multiple electrode recording to demonstrate that the orientation tuning of single
      cells in primary visual cortex is reliably related to the local structure of the
      orientation preference map in both cats and monkeys.

PMID- 18341983
TI  - Hotheaded: TRPV1 as mediator of hippocampal synaptic plasticity.
AB  - TRPV1 is a sensory transduction channel that mediates thermal nociception and
      some aspects of pathological pain. In this issue of Neuron, Gibson et al. report
      that TRPV1 also plays important roles in hippocampal synaptic plasticity,
      presenting a potential challenge for TRPV1-targeted therapeutics for the
      treatment of pain.

PMID- 18341984
TI  - Mesoprefrontal dopamine neurons distinguish themselves.
AB  - By distinguishing groups of dopamine neurons that differ in their projection
      patterns and intrinsic properties, Lammel and colleagues report in this issue of
      Neuron that mesocorticolimbic dopamine neurons of the ventral tegmental area
      (VTA) form a distinct subclass of dopamine cells.

PMID- 18341985
TI  - Cocaine-paired cues activate aversive representations in accumbens neurons.
AB  - Aversive states are proposed to drive addiction. Here, Wheeler and colleagues
      show that drug-associated cues come to activate neural representations of
      aversive information in nucleus accumbens and that this activation predicts
      subsequent drug use. These remarkable data identify a potential neural substrate
      through which aversive affective representations may motivate drug use.

PMID- 18341987
TI  - Fast three-dimensional fluorescence imaging of activity in neural populations by
      objective-coupled planar illumination microscopy.
AB  - Unraveling the functions of the diverse neural types in any local circuit
      ultimately requires methods to record from most or all of its cells
      simultaneously. One promising approach to this goal is fluorescence imaging, but
      existing methods using laser-scanning microscopy (LSM) are severely limited in
      their ability to resolve rapid phenomena, like neuronal action potentials, over
      wide fields. Here we present a microscope that rapidly sections a three
      dimensional volume using a thin illumination sheet whose position is rigidly
      coupled to the objective and aligned with its focal plane. We demonstrate that
      this approach allows exceptionally low-noise imaging of large neuronal
      populations at pixel rates at least 100-fold higher than with LSM. Using this
      microscope, we studied the pheromone-sensing neurons of the mouse vomeronasal
      organ and found that responses to dilute urine are largely or exclusively
      restricted to cells in the apical layer, the location of V1r-family-expressing
      neurons.

PMID- 18341986
TI  - Genetic dissection of neural circuits.
AB  - Understanding the principles of information processing in neural circuits
      requires systematic characterization of the participating cell types and their
      connections, and the ability to measure and perturb their activity. Genetic
      approaches promise to bring experimental access to complex neural systems,
      including genetic stalwarts such as the fly and mouse, but also to nongenetic
      systems such as primates. Together with anatomical and physiological methods,
      cell-type-specific expression of protein markers and sensors and transducers will
      be critical to construct circuit diagrams and to measure the activity of
      genetically defined neurons. Inactivation and activation of genetically defined
      cell types will establish causal relationships between activity in specific
      groups of neurons, circuit function, and animal behavior. Genetic analysis thus
      promises to reveal the logic of the neural circuits in complex brains that guide
      behaviors. Here we review progress in the genetic analysis of neural circuits and
      discuss directions for future research and development.

PMID- 18341988
TI  - Neuronal selectivity and local map structure in visual cortex.
AB  - The organization of primary visual cortex (V1) into functional maps makes
      individual cells operate in a variety of contexts. For instance, some neurons lie
      in regions of fairly homogeneous orientation preference (iso-orientation
      domains), while others lie in regions with a variety of preferences (e.g.,
      pinwheel centers). We asked whether this diversity in local map structure
      correlates with the degree of selectivity of spike responses. We used a
      combination of imaging and electrophysiology to reveal that neurons in regions of
      homogeneous orientation preference have much sharper tuning. Moreover, in both
      monkeys and cats, a common principle links the structure of the orientation map,
      on the spatial scale of dendritic integration, to the degree of selectivity of
      individual cells. We conclude that neural computation is not invariant across the
      cortical surface. This finding must factor into future theories of receptive
      field wiring and map development.

PMID- 18341989
TI  - Transcriptional regulation of beta-secretase by p25/cdk5 leads to enhanced
      amyloidogenic processing.
AB  - Cyclin-dependent kinase 5 (cdk5) has been implicated in Alzheimer's disease (AD)
      pathogenesis. Here, we demonstrate that overexpression of p25, an activator of
      cdk5, led to increased levels of BACE1 mRNA and protein in vitro and in vivo. A
      p25/cdk5 responsive region containing multiple sites for signal transducer and
      activator of transcription (STAT1/3) was identified in the BACE1 promoter. STAT3
      interacts with the BACE1 promoter, and p25-overexpressing mice had elevated
      levels of pSTAT3 and BACE1, whereas cdk5-deficient mice had reduced levels.
      Furthermore, mice with a targeted mutation in the STAT3 cdk5 responsive site had
      lower levels of BACE1. Increased BACE levels in p25 overexpressing mice
      correlated with enhanced amyloidogenic processing that could be reversed by a
      cdk5 inhibitor. These data demonstrate a pathway by which p25/cdk5 increases the
      amyloidogenic processing of APP through STAT3-mediated transcriptional control of
      BACE1 that could have implications for AD pathogenesis.

PMID- 18341990
TI  - The transmembrane protein Golden goal regulates R8 photoreceptor axon-axon and
      axon-target interactions.
AB  - During Drosophila visual system development, photoreceptor (R) axons choose their
      correct paths and targets in a step-wise fashion. R axons with different
      identities make specific pathfinding decisions at different stages during
      development. We show here that the transmembrane protein Golden goal (Gogo),
      which is dynamically expressed in all R neurons and localizes predominantly to
      growth cones, is required in two distinct steps of R8 photoreceptor axon
      pathfinding: Gogo regulates axon-axon interactions and axon-target interactions
      in R8 photoreceptor axons. gogo loss-of-function and gain-of-function phenotypes
      suggest that Gogo mediates repulsive axon-axon interaction between R8 axons to
      maintain their proper spacing, and it promotes axon-target recognition at the
      temporary layer to enable R8 axons to enter their correct target columns in the
      medulla. From detailed structure-function experiments, we propose that Gogo
      functions as a receptor that binds an unidentified ligand through its conserved
      extracellular domain.

PMID- 18341991
TI  - Rapid activity-dependent modifications in synaptic structure and function require
      bidirectional Wnt signaling.
AB  - Activity-dependent modifications in synapse structure play a key role in synaptic
      development and plasticity, but the signaling mechanisms involved are poorly
      understood. We demonstrate that glutamatergic Drosophila neuromuscular junctions
      undergo rapid changes in synaptic structure and function in response to patterned
      stimulation. These changes, which depend on transcription and translation,
      include formation of motile presynaptic filopodia, elaboration of
      undifferentiated varicosities, and potentiation of spontaneous release frequency.
      Experiments indicate that a bidirectional Wnt/Wg signaling pathway underlies
      these changes. Evoked activity induces Wnt1/Wg release from synaptic boutons,
      which stimulates both a postsynaptic DFz2 nuclear import pathway as well as a
      presynaptic pathway involving GSK-3beta/Shaggy. Our findings suggest that
      bidirectional Wg signaling operates downstream of synaptic activity to induce
      modifications in synaptic structure and function. We propose that activation of
      the postsynaptic Wg pathway is required for the assembly of the postsynaptic
      apparatus, while activation of the presynaptic Wg pathway regulates cytoskeletal
      dynamics.

PMID- 18341992
TI  - The subspine organization of actin fibers regulates the structure and plasticity
      of dendritic spines.
AB  - Synapse function and plasticity depend on the physical structure of dendritic
      spines as determined by the actin cytoskeleton. We have investigated the
      organization of filamentous (F-) actin within individual spines on CA1 pyramidal
      neurons in rat hippocampal slices. Using two-photon photoactivation of green
      fluorescent protein fused to beta-actin, we found that a dynamic pool of F-actin
      at the tip of the spine quickly treadmilled to generate an expansive force. The
      size of a stable F-actin pool at the base of the spine depended on spine volume.
      Repeated two-photon uncaging of glutamate formed a third pool of F-actin and
      enlarged the spine. The spine often released this "enlargement pool" into the
      dendritic shaft, but the pool had to be physically confined by a spine neck for
      the enlargement to be long-lasting. Ca2+/calmodulin-dependent protein kinase II
      regulated this confinement. Thus, spines have an elaborate mechanical nature that
      is regulated by actin fibers.

PMID- 18341993
TI  - Accumulation of AMPA receptors in autophagosomes in neuronal axons lacking
      adaptor protein AP-4.
AB  - AP-4 is a member of the adaptor protein complexes, which control vesicular
      trafficking of membrane proteins. Although AP-4 has been suggested to contribute
      to basolateral sorting in epithelial cells, its function in neurons is unknown.
      Here, we show that disruption of the gene encoding the beta subunit of AP-4
      resulted in increased accumulation of axonal autophagosomes, which contained AMPA
      receptors and transmembrane AMPA receptor regulatory proteins (TARPs), in axons
      of hippocampal neurons and cerebellar Purkinje cells both in vitro and in vivo.
      AP-4 indirectly associated with the AMPA receptor via TARPs, and the specific
      disruption of the interaction between AP-4 and TARPs caused the mislocalization
      of endogenous AMPA receptors in axons of wild-type neurons. These results
      indicate that AP-4 may regulate proper somatodendritic-specific distribution of
      its cargo proteins, including AMPA receptor-TARP complexes and the autophagic
      pathway in neurons.

PMID- 18341995
TI  - Unique properties of mesoprefrontal neurons within a dual mesocorticolimbic
      dopamine system.
AB  - The mesocorticolimbic dopamine system is essential for cognitive and emotive
      brain functions and is thus an important target in major brain diseases like
      schizophrenia, drug addiction, and attention deficit hyperactivity disorder.
      However, the cellular basis for the diversity in behavioral functions and
      associated dopamine-release pattern within the mesocorticolimbic system has
      remained unclear. Here, we report the identification of a type of dopaminergic
      neuron within the mesocorticolimbic dopamine system with unconventional fast
      firing properties and small DAT/TH mRNA expression ratios that selectively
      projects to prefrontal cortex and nucleus accumbens core and medial shell as well
      as to basolateral amygdala. In contrast, well-described conventional slow-firing
      dopamine midbrain neurons only project to the lateral shell of the nucleus
      accumbens and the dorsolateral striatum. Among this dual dopamine midbrain system
      defined in this study by converging anatomical, electrophysiological, and
      molecular properties, mesoprefrontal dopaminergic neurons are unique, as only
      they do not possess functional somatodendritic Girk2-coupled dopamine D2
      autoreceptors.

PMID- 18341994
TI  - TRPV1 channels mediate long-term depression at synapses on hippocampal
      interneurons.
AB  - TRPV1 receptors have classically been defined as heat-sensitive, ligand-gated,
      nonselective cation channels that integrate nociceptive stimuli in sensory
      neurons. TRPV1 receptors have also been identified in the brain, but their
      physiological role is poorly understood. Here we report that TRPV1 channel
      activation is necessary and sufficient to trigger long-term synaptic depression
      (LTD). Excitatory synapses onto hippocampal interneurons were depressed by either
      capsaicin, a potent TRPV1 channel activator, or the endogenously released
      eicosanoid, 12-(S)-HPETE, whereas neighboring excitatory synapses onto CA1
      pyramidal cells were unaffected. TRPV1 receptor antagonists also prevented
      interneuron LTD. In brain slices from TRPV1-/- mice, LTD was absent, and neither
      capsaicin nor 12-(S)-HPETE elicited synaptic depression. Our results suggest
      that, in the hippocampus, TRPV1 receptor activation selectively modifies synapses
      onto interneurons. Like other forms of hippocampal synaptic plasticity, TRPV1
      mediated LTD may have a role in long-term changes in physiological and
      pathological circuit behavior during learning and epileptic activity.

PMID- 18341996
TI  - Behavioral and electrophysiological indices of negative affect predict cocaine
      self-administration.
AB  - The motivation to seek cocaine comes in part from a dysregulation of reward
      processing manifested in dysphoria, or affective withdrawal. Learning is a
      critical aspect of drug abuse; however, it remains unclear whether drug
      associated cues can elicit the emotional withdrawal symptoms that promote cocaine
      use. Here we report that a cocaine-associated taste cue elicited a conditioned
      aversive state that was behaviorally and neurophysiologically quantifiable and
      predicted subsequent cocaine self-administration behavior. Specifically, brief
      intraoral infusions of a cocaine-predictive flavored saccharin solution elicited
      aversive orofacial responses that predicted early-session cocaine taking in rats.
      The expression of aversive taste reactivity also was associated with a shift in
      the predominant pattern of electrophysiological activity of nucleus accumbens
      (NAc) neurons from inhibitory to excitatory. The dynamic nature of this
      conditioned switch in affect and the neural code reveals a mechanism by which
      cues may exert control over drug self-administration.

PMID- 18341997
TI  - Separable substrates for anticipatory and consummatory food chemosensation.
AB  - Perception of the smell of a food precedes its ingestion and perception of its
      flavor. The neurobiological underpinnings of this association are not well
      understood. Of central interest is whether the same neural circuits code for
      anticipatory and consummatory phases. Here, we show that the amygdala and
      mediodorsal thalamus respond preferentially to food odors that predict immediate
      arrival of their associated drink (FO+) compared to food odors that predict
      delivery of a tasteless solution (FO-) and compared to the receipt of the drink.
      In contrast, the left insula/operculum responds preferentially to the drink,
      whereas the right insula/operculum and left orbitofrontal cortex respond to FO+
      and drink. These findings indicate separable and overlapping representation of
      anticipatory and consummatory chemosensation. Moreover, since ratings of
      perceived pleasantness of FO+, FO-, and drink were similar, the response in the
      amygdala and thalamus cannot reflect acquired affective value but rather
      predictive meaning or biological relevance.

PMID- 18341998
TI  - The NLR gene family: a standard nomenclature.

PMID- 18341999
TI  - T testing the immune system.
AB  - Amid the flurry of grant writing and experimentation, statistical analysis
      sometimes gets less attention than it requires. Here, we describe fully the
      considerations that should go into the employment of the statistical two-sample t
      test.

PMID- 18342000
TI  - Baseless assumptions: activation of TLR9 by DNA.
AB  - The Toll-like receptor 9 (TLR9) is activated by DNA presented in acidified,
      intracellular compartments. Previous studies suggested that signaling required
      unmethylated CpG dinucleotides, but in this issue of Immunity, Haas et al. (2008)
      challenge this view, showing that DNA can activate TLR9 in a sequence-independent
      manner.

PMID- 18342001
TI  - Multitasking of interferon regulatory factor-4 in early B cells.
AB  - Immunoglobulin heavy- and light-chain genes are rearranged in a temporally
      ordered manner. In this issue, Johnson et al. (2008) show that interferon
      regulatory factor-4 regulates light-chain gene rearrangement by activating
      enhancers and attenuating interleukin-7 signaling.

PMID- 18342002
TI  - Thymus lineage commitment: a single switch.
AB  - In this issue of Immunity, He et al. (2008) establish the logic and circuitry
      that determine CD4-CD8 lineage specification. It all comes down to an eighty base
      pair silencer switch.

PMID- 18342003
TI  - Living in context with the survival factor BAFF.
AB  - In this issue, Gardham et al. (2008) show that BAFF, a tumor necrosis factor
      (TNF) family member, promotes B cell survival by hindering interactions between
      TNF-receptor-associated factors, blocking their negative regulation of
      nonclassical NF-kappaB activity.

PMID- 18342004
TI  - Neuropilin-1: the glue between regulatory T cells and dendritic cells?
AB  - The interaction between dendritic cells and regulatory T cells is critical for
      the maintenance of self-tolerance. In this issue of Immunity, Sarris et al.
      (2008) find that Neuropilin-1 contributes to the prolonged interaction of
      regulatory T cells with dendritic cells.

PMID- 18342005
TI  - The fidelity, occasional promiscuity, and versatility of T cell receptor
      recognition.
AB  - Although there are multiple structures showing how alphabeta T cell receptors
      (TCRs) specifically recognize antigenic peptides bound to the major
      histocompatibility complex (MHC) molecules (pMHC-I and pMHC-II), we have little
      data on how TCRs interact with lipid-based antigens presented by members of the
      CD1 family. Here, we review recent findings in the field of TCR recognition,
      including TCR-pMHC complexes and the structure of a TCR in complex with CD1d
      glycolipid. Collectively, these studies have revealed the versatility of the TCR
      in recognizing the distinct yet evolutionarily related proteinaceous and lipid
      presenting molecules of the immune system.

PMID- 18342006
TI  - The DNA sugar backbone 2' deoxyribose determines toll-like receptor 9 activation.
AB  - CpG motifs within phosphorothioate (PS)-modified DNA drive Toll-like receptor 9
      (TLR9) activation, but the rules governing recognition of natural phosphodiester
      (PD) DNA are less understood. Here, we showed that the sugar backbone determined
      DNA recognition by TLR9. Homopolymeric, base-free PD 2' deoxyribose acted as a
      basal TLR9 agonist as it bound to and activated TLR9. This effect was enhanced by
      DNA bases, even short of CpG motifs. In contrast, PS-modified 2' deoxyribose
      homopolymers acted as TLR9 and TLR7 antagonists. They displayed high affinity to
      both TLRs and did not activate on their own, but they competitively inhibited
      ligand-TLR interaction and activation. Although addition of random DNA bases to
      the PS 2' deoxyribose backbone did not alter these effects, CpG motifs
      transformed TLR9-inhibitory to robust TLR9-stimulatory activity. Our results
      identified the PD 2' deoxyribose backbone as an important determinant of TLR9
      activation by natural DNA, restrict CpG-motif dependency of TLR9 activation to
      synthetic PS-modified ligands, and define PS-modified 2' deoxyribose as a prime
      effector of TLR9 and TLR7 inhibition.

PMID- 18342007
TI  - CD4-CD8 lineage commitment is regulated by a silencer element at the ThPOK
      transcription-factor locus.
AB  - The transcription factor ThPOK is necessary and sufficient to trigger adoption of
      the CD4 lymphocyte fate. Here we investigate the regulation of ThPOK expression
      and its subsequent control of CD4+ T cell commitment. Treatment of immature
      thymocytes with anti-TCR (T cell receptor) showed that TCR signals were important
      in ThPOK induction and that the CD4+8lo stage was the likely target of the
      inductive TCR signal. We identified at the ThPOK locus a key distal regulatory
      element (DRE) that mediated its differential expression in class I- versus II
      restricted CD4+8lo thymocytes. The DRE was both necessary for suppression of
      ThPOK expression in class I-restricted thymocytes and sufficient for its
      induction in class II-restricted thymocytes. Mutagenesis analysis defined an
      essential 80bp core DRE sequence and its potential regulatory motifs. We propose
      a silencer-dependent model of lineage choice, whereby inactivation of the DRE
      silencer by a strong TCR signal leads to CD4 commitment, whereas continued
      silencer activity leads to CD8 commitment.

PMID- 18342008
TI  - Complementation in trans of altered thymocyte development in mice expressing
      mutant forms of the adaptor molecule SLP76.
AB  - The adaptor protein SLP76 directs signaling downstream of the T cell receptor
      (TCR) and is essential for thymocyte development. SLP76 contains three N-terminal
      tyrosines that are critical for its function. To define the role of these
      residues in thymocyte development, we generated two lines of "knock-in" mice, one
      expressing a mutation in tyrosine 145 (Y145F) and a second harboring two point
      mutations at tyrosines 112 and 128 (Y112-128F). We show here that although
      thymocyte development requires both Y145- and Y112-128-generated signals,
      selection was more dependent upon Y145. Although several proximal TCR signaling
      events were defective in both mutant mice, phosphorylation of the guanine
      nucleotide exchange factor, Vav1, and activation of Itk-dependent pathways were
      differentially affected by mutations at Y112-128 and Y145, respectively. Analysis
      of mice expressing one Y145F and one Y112-128F allele revealed that these mutants
      could complement one another in trans, demonstrating cooperativity between two or
      more SLP76 molecules. Thus, the N-terminal tyrosines of SLP76 are required for
      thymocyte selection but can function on separate molecules to support TCR
      signaling.

PMID- 18342010
TI  - Restoring the association of the T cell receptor with CD8 reverses anergy in
      human tumor-infiltrating lymphocytes.
AB  - For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL)
      clones exhibit a decrease in their effector activity and in their binding to
      human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this
      state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8.
      Effector function and TCR-CD8 colocalization were restored with galectin
      disaccharide ligands, suggesting that the binding of TCR to galectin plays a role
      in the distancing of TCR from CD8. These findings appear to be applicable in
      vivo, as TCR was observed to be distant from CD8 on human tumor-infiltrating
      lymphocytes, which were anergic. These lymphocytes recovered effector functions
      and TCR-CD8 colocalization after ex vivo treatment with galectin disaccharide
      ligands. The separation of TCR and CD8 molecules could be one major mechanism of
      anergy in tumors and other chronic stimulation conditions.

PMID- 18342009
TI  - The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization
      domain containing 2-triggered signals.
AB  - Muramyl dipeptide (MDP), a product of bacterial cell-wall peptidoglycan,
      activates innate immune cells by stimulating nucleotide-binding oligomerization
      domain containing 2 (NOD2) -dependent activation of the transcription factor
      NFkappaB and transcription of proinflammatory genes. A20 is a ubiquitin-modifying
      enzyme that restricts tumor necrosis factor (TNF) receptor and Toll-like receptor
      (TLR) -induced signals. We now show that MDP induces ubiquitylation of receptor-
      interacting protein 2 (RIP2) in primary macrophages. A20-deficient cells exhibit
      dramatically amplified responses to MDP, including increased RIP2 ubiquitylation,
      prolonged NFkappaB signaling, and increased production of proinflammatory
      cytokines. In addition, in vivo responses to MDP are exaggerated in A20-deficient
      mice and in chimeric mice bearing A20-deficient hematopoietic cells. These
      exaggerated responses occur independently of the TLR adaptors MyD88 and TRIF as
      well as TNF signals. These findings indicate that A20 directly restricts NOD2
      induced signals in vitro and in vivo, and provide new insights into how these
      signals are physiologically restricted.

PMID- 18342011
TI  - Structure analysis of the fourth transmembrane domain of Nramp1 in model
      membranes.
AB  - Nramp1 (natural resistance-associated macrophage protein 1) is an integral
      membrane protein with 12 putative transmembrane domains. As a proton-coupled
      divalent metal cation transporter, it is involved in defense against
      intracellular pathogens. Disease-causing mutation in Nramp1 occurring at glycine
      169 located within the fourth transmembrane domain (TM4) suggests functional
      importance of this domain. In this paper, we study the three-dimensional
      structures of a peptide, corresponding to the TM4 of the wild-type Nramp1, in SDS
      micelles and 2, 2, 2-trifluoroethanol solvent using CD and NMR spectroscopies. We
      have found that an alpha-helix is predominantly induced in membrane-mimetic
      environments and the folding of the C-terminal residues is regulated by pH in SDS
      micelles. The peptide is embedded in SDS micelles and self-associated by coiled
      coil interactions. The helix of the peptide in TFE is lengthened towards the N
      terminus compared with those in SDS micelles at acidic pH and the self
      association of the peptide is also observed in TFE. The fact that Mn(2+) ions are
      accessible to Asp-14 located in the interior of SDS micelles is found and the
      binding affinity is increased with increasing pH. The self-association of the
      peptide may provide a path by which Mn(2+) ions pass through the membrane.

PMID- 18342012
TI  - Preanalytical venous blood sampling practices demand improvement--a survey of
      test-request management, test-tube labelling and information search procedures.
AB  - BACKGROUND: Most errors in laboratory medicine are preanalytical in nature. In
      the present study, we aimed to survey preanalytical steps in venous blood
      sampling, prior to actual sample collection. These steps included test-request
      management and test-tube labelling, as well as information search procedures.
      METHODS: Venous blood sampling staff (n=314, response rate 94%) in hospital wards
      and laboratories completed a questionnaire related to clinical chemistry testing.
      RESULTS: Instructions for test-request management and test-tube labelling were
      not always followed. For example, only 66% of the ward staff reported always
      checking the test-request if someone else completed it, compared to 90% of the
      laboratory staff (p=0.003). As few as 16% of the ward staff reported desirable
      practices regarding test-tube labelling, compared to 100% of the laboratory staff
      (p<0.001). Furthermore, 18% of the ward staff reported always using online
      manuals (the only source of updated information), compared to 63% of the
      laboratory staff (p<0.001). CONCLUSIONS: Our results indicate a substantial risk
      of preanalytical error in test-request management, test-tube labelling, and
      information search practices, particularly in the wards. Our findings thus
      underscore the importance of quality control in venous blood sampling, in order
      to increase patient safety in modern health care.

PMID- 18342013
TI  - Factor V Leiden: is it the chief contributor to activated protein C resistance in
      Asian-Indian patients with deep vein thrombosis?
AB  - BACKGROUND: Deep vein thrombosis is a condition, which has several acquired as
      well as genetic causes. One of the most common reasons for deep vein thrombosis
      is activated protein C resistance caused by Factor V Leiden. METHOD: We examined
      the risk posed by Factor V Leiden, Hong Kong/Cambridge and HR2 Haplotype
      mutations in 155 deep vein thrombosis patients and 120 healthy controls in the
      background of activated protein C resistance. RESULT: Thirty-one of our patients
      showed activated protein C resistance of which only 16 carried Factor V Leiden
      mutation which was a far lower number than what is usually seen in Caucasian
      population. Factor V Leiden mutation was significantly associated with the risk
      of deep vein thrombosis (Yates corrected p-value=0.002; 95%CI; odds ratio: 13.7).
      Factor V Hong Kong/Cambridge and HR2 Haplotype were not found to be associated
      with the risk of deep vein thrombosis. There is a possibility that Factor V HR2
      Haplotype might also be associated with activated protein C resistance even in
      the absence of Factor V Leiden. CONCLUSIONS: Factor V Leiden mutation was seen to
      contribute far less towards activated protein C resistance in Asian-Indian deep
      vein thrombosis patients than what has been commonly observed in Caucasians.

PMID- 18342014
TI  - Retinoic acid induces caspase-8 transcription via phospho-CREB and increases
      apoptotic responses to death stimuli in neuroblastoma cells.
AB  - Caspase-8 is frequently deleted or silenced in neuroblastoma and other solid
      tumor such as medulloblastoma and small cell lung carcinoma. Caspase-8 expression
      can be re-established in neuroblastoma cell lines by treatment with demethylating
      agents or with IFN-gamma. Here we show that four different retinoic acid (RA)
      derivatives also increase caspase-8 protein expression in neuroblastoma,
      medulloblastoma and small cell lung carcinoma cell lines. This increase in
      protein expression is mirrored by an increase in RNA expression in NB cells.
      However, the promoter region of the caspase-8 gene was not responsible for the
      induction of caspase-8 expression. Rather, we identified another intronic region
      containing a CREB binding site that was required for maximal induction of caspase
      8 via RA. DNA-protein interaction assays revealed increased phospho-CREB binding
      to this response element in RA-treated NB cells. Furthermore, mutations of the
      CREB binding site completely blocked caspase-8 induction in the luciferase
      reporter system assay and transfection of dominant-negative form of CREB
      repressed the up-regulation of caspase-8 by RA. Importantly, RA-released cells
      maintained caspase-8 expression for at least 2-5 days and were more sensitive to
      doxorubicin and TNFalpha. Thus, RA treatment in conjunction with TNFalpha and/or
      subsets of cytotoxic agents may have therapeutic benefits.

PMID- 18342015
TI  - Examination of intrinsic sulfonamide resistance in Bacillus anthracis: a novel
      assay for dihydropteroate synthase.
AB  - Dihydropteroate synthase (DHPS) catalyzes the formation of dihydropteroate and Mg
      pyrophosphate from 6-hydroxymethyl-7,8-dihydropterin diphosphate and para
      aminobenzoic acid. The Bacillus anthracis DHPS is intrinsically resistant to
      sulfonamides. However, using a radioassay that monitors the dihydropteroate
      product, the enzyme was inhibited by the same sulfonamides. A continuous
      spectrophotometric assay for measuring the enzymatic activity of DHPS was
      developed and used to examine the effects of sulfonamides on the enzyme. The new
      assay couples the production of MgPPi to the pyrophosphate-dependent
      phosphofructokinase/aldolase/triose isomerase/alpha-glycerophosphate
      dehydrogenase reactions and monitors the disappearance of NADH at 340nm. The
      coupled enzyme assay demonstrates that resistance of the B. anthracis DHPS
      results in part from the use of the sulfonamides as alternative substrates,
      resulting in the formation of sulfonamide-pterin adducts, and not necessarily due
      to an inability to bind them.

PMID- 18342016
TI  - Increased urinary 1,N6-ethenodeoxyadenosine and 3,N4-ethenodeoxycytidine
      excretion in thalassemia patients: markers for lipid peroxidation-induced DNA
      damage.
AB  - Thalassemic diseases including homozygous beta-thalassemia and beta
      thalassemia/Hb E (beta-Thal/Hb E) are prevalent in Southeast Asia. Iron overload
      is a common complication in beta-thalassemia patients which induces intracellular
      oxidative stress and lipid peroxidation (LPO). LPO end products generate
      miscoding etheno adducts in DNA which after their repair are excreted in urine.
      We investigated whether urinary levels of 1,N6-ethenodeoxyadenosine (epsilondA)
      and 3,N4-ethenodeoxycytidine (epsilondC) can serve as putative cancer risk
      markers in beta-Thal/Hb E patients. epsilondA and epsilondC levels were assayed
      in collected urine samples by immunoprecipitation-HPLC-fluorescence and 32P
      postlabeling TLC, respectively. Mean epsilondA (fmol/micromol creatinine) levels
      in urine of beta-Thal/Hb E patients ranged from 4.8 to 120.4 (33.8+/-3.9; n=37)
      and were 8.7 times higher compared to asymptomatic controls (1.4-13.8; 3.9+/-0.8;
      n=20). The respective epsilondC levels ranged from 0.15 to 32.5 (5.2+/-1.3; n=37)
      and were increased some 13 times over controls (0.04-1.2; 0.4+/-0.7; n=20).
      epsilondC levels were correlated positively with NTBI (r=0.517; P=0.002), whereas
      epsilondA showed only a trend (r=0.257; P=0.124). We conclude that the strongly
      increased urinary excretion of etheno adducts indicates elevated LPO-induced DNA
      damage in internal organs such as the liver. These highly promutagenic lesions
      may contribute to the increased risk of thalassemia patients to develop
      hepatocellular carcinoma.

PMID- 18342018
TI  - Vitamin B12b enhances the cytotoxicity of dithiothreitol.
AB  - It has been found previously that vitamin B12b amplifies significantly the
      cytotoxic effects of ascorbic acid by catalyzing the formation of reactive oxygen
      species, and the antioxidant dithiothreitol (DTT), in contrast to catalase, does
      not prevent the cytotoxicity. Therefore, in this study we examined whether B12b
      is able to enhance the cytotoxicity of DTT. It was revealed that B12b strongly
      increases the cytotoxic effect of DTT. Vitamin B12b added to DTT catalyzed the
      generation and drastic accumulation of hydrogen peroxide in culture medium to a
      concentration of 260 microM within 7 min. The extracellular oxidative burst
      induced by the combination of B12b and DTT (DTT + B12b) was accompanied by
      intracellular oxidative stress, the destabilization of lysosomes, and damage to
      DNA. The accumulation of DNA lesions led to the initiation of apoptotic cell
      death, including the activation of caspase-3 and the release of cytochrome c. The
      antioxidants pyruvate and catalase completely prevented the DTT + B12b-induced
      oxidative stress and cell death. The iron chelators desferrioxamine and
      phenanthroline prevented the geno- and cytotoxic action of the combination
      although they did not reduce the exogenous oxidative burst, indicating a key role
      for intracellular iron in the cytotoxicity of the combination. Thus, vitamin B12b
      dramatically enhances the cytotoxicity of DTT, catalyzing the generation of
      hydrogen peroxide and inducing extra- and intracellular oxidative stress, early
      destabilization of lysosomes, and iron-dependent DNA damage.

PMID- 18342017
TI  - Role of reactive oxygen species in the neurotoxicity of environmental agents
      implicated in Parkinson's disease.
AB  - Among age-related neurodegenerative diseases, Parkinson's disease (PD) represents
      the best example for which oxidative stress has been strongly implicated. The
      etiology of PD remains unknown, yet recent epidemiological studies have linked
      exposure to environmental agents, including pesticides, with an increased risk of
      developing the disease. As a result, the environmental hypothesis of PD has
      developed, which speculates that chemical agents in the environment are capable
      of producing selective dopaminergic cell death, thus contributing to disease
      development. The use of environmental agents such as 1-methyl-4-phenyl-1,2,3,6
      tetrahydropyridine, rotenone, paraquat, dieldrin, and maneb in toxicant-based
      models of PD has become increasingly popular and provided valuable insight into
      the neurodegenerative process. Understanding the unique and shared mechanisms by
      which these environmental agents act as selective dopaminergic toxicants is
      critical in identifying pathways involved in PD pathogenesis. In this review, we
      discuss the neurotoxic properties of these compounds with specific focus on the
      induction of oxidative stress. We highlight landmark studies along with recent
      advances that support the role of reactive oxygen and reactive nitrogen species
      from a variety of cellular sources as potent contributors to the neurotoxicity of
      these environmental agents. Finally, human risk and the implications of these
      studies in our understanding of PD-related neurodegeneration are discussed.

PMID- 18342020
TI  - Allosteric modulation of kinases and GPCRs: design principles and structural
      diversity.
AB  - Allosteric binding sites, as opposed to traditional orthosteric binding sites,
      offer unparalleled opportunities for drug discovery by providing high levels of
      selectivity, mimicking physiological conditions, affording fewer side effects
      because of desensitization/downregulation, and engendering ligands with
      chemotypes divergent from orthosteric ligands. For kinases, allosteric mechanisms
      described to date include alteration of protein kinase conformation blocking
      productive ATP binding which appear 'ATP competitive' or blocking kinase
      activation by conformational changes that are 'ATP non-competitive'. For GPCRs,
      allosteric mechanisms impart multiple modes of target modulation (positive
      allosteric modulation (PAM), negative allosteric modulation (NAM), neutral
      cooperativity, partial antagonism (PA), allosteric agonism and allosteric
      antagonism). Here, we review recent developments in the design principles and
      structural diversity of allosteric ligands for kinases and GPCRs.

PMID- 18342019
TI  - Influence of PDZK1 on lipoprotein metabolism and atherosclerosis.
AB  - PDZK1 is a scaffold protein containing four PDZ protein interaction domains,
      which bind to the carboxy termini of a number of membrane transporter proteins,
      including ion channels (e.g., CFTR) and cell surface receptors. One of these, the
      HDL receptor, scavenger receptor class B type I (SR-BI), exhibits a striking,
      tissue-specific dependence on PDZK1 for its expression and activity. In PDZK1
      knockout (KO) mice there is a marked reduction of SR-BI protein expression
      (approximately 95%) in the liver, but not in steroidogenic tissues or, as we show
      in this report, in bone marrow- or spleen-derived macrophages, or lung-derived
      endothelial cells. Because of hepatic SR-BI deficiency, PDZK1 KO mice exhibit
      dyslipidemia characterized by elevated plasma cholesterol carried in abnormally
      large HDL particles. Here, we show that inactivation of the PDZK1 gene promotes
      the development of aortic root atherosclerosis in apolipoprotein E (apoE) KO mice
      fed with a high fat/high cholesterol diet. However, unlike complete SR-BI
      deficiency in SR-BI/apoE double KO mice, PDZK1 deficiency in PDZK1/apoE double
      knockout mice did not result in development of occlusive coronary artery disease
      or myocardial infarction, presumably because of their residual expression of SR
      BI. These findings demonstrate that deficiency of an adaptor protein essential
      for normal expression of a lipoprotein receptor promotes atherosclerosis in a
      murine model. They also define PDZK1 as a member of the family of proteins that
      is instrumental in preventing cardiovascular disease by maintaining normal
      lipoprotein metabolism.

PMID- 18342021
TI  - Locating the rate-determining step(s) for three-step hydrolase-catalyzed
      reactions with DYNAFIT.
AB  - Hydrolytic reactions of oligopeptide 4-nitroanilides catalyzed by human-alpha
      thrombin, human activated protein C and human factor Xa were studied at pH 8.0
      8.4 and 25.0+/-0.1 degrees C by the progress curve method and individual rate
      constants were calculated mostly within 10% internal error using DYNAFITV. A
      systematic strategy has been developed for fitting a three-step consecutive
      mechanism to eighteen hundred to six thousand time-course data points polled from
      two to four independent kinetic experiments. Enzyme and substrate concentrations
      were also calculated. Individual rate constants well reproduce published values
      obtained under comparable conditions and the Michaelis-Menten kinetic parameters
      calculated from these elementary rate constants are also within reasonable limits
      of published values. For comparison, the integrated Michaelis-Menten equation was
      also fitted to data from twelve sets. Both the k(cat) and k(cat)/K(m) values are
      within 15% agreement with those calculated using the elementary rate constants
      obtained with DYNAFITV. Rate constants for the second and third consecutive steps
      are within 3-4 fold indicating that both determine the overall rate. The Factor
      Xa-catalyzed hydrolysis of N-alpha-Z-D-Arg-Gly-Arg-pNA.2HCl at pH 8.4 in a series
      of buffers containing increasing fractions of deuterium at 25.0+/-0.1 degrees C
      shows a very strong dependence of k(3) and a moderate dependence of k(2) on D
      content in the buffer: the fractionation factors are: 0.49+/-0.03 for K(1,)
      0.70+/-0.05 for k(2), and (0.32+/-0.03)(2) for k(3).

PMID- 18342022
TI  - Transcriptional regulation of the 5'-flanking region of the human transcription
      factor Sp3 gene by NF-1, c-Myb, B-Myb, AP-1 and E2F.
AB  - We analyzed in detail the proximal promoter of transcription factor Sp3, which
      expands 281 bp from the translational start. This sequence contains putative
      binding sites for Sp1, NF-Y, NF-1, Myb, AP-1 and E2F transcription factors. In
      this work, we further explored the role of these boxes on the regulation of the
      Sp3 gene. Gel-shift and competition assays showed specific binding of NF-1, Myb,
      AP-1 and E2F. Furthermore, chromatin immunoprecipitation assays demonstrated that
      Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb, c-Jun and E2F1 actually occupied the Sp3
      promoter in HeLa cells. Transient transfections and luciferase assays revealed
      activation of the Sp3 proximal promoter upon overexpression of NF-1, c-Myb, B
      Myb, c-Jun and c-Fos, and repression after overexpression of E2F/DP1. Point
      mutation of the binding sites for NF1, Myb, AP1 and E2F and cell incubation with
      specific siRNAs further confirmed the role of these transcription factors in the
      regulation of the Sp3 promoter. The regulation of the endogenous Sp3 gene was
      also observed at the mRNA level when the studied transcription factors were
      overexpressed or knocked down by siRNA incubation. These results help to explain
      the complex regulation of the Sp3 gene, which depends, at least in part, on the
      relative amount of Sp1, Sp3, NF-Y, NF-1, c-Myb, B-Myb, AP-1, and E2F proteins in
      the cell.

PMID- 18342023
TI  - Evolution of microRNAs and their targets: are all microRNAs biologically
      relevant?
AB  - MicroRNAs (miRNAs) are defined by their precise processing from a longer stem
      loop precursor and by their subsequent ability to direct the regulation of target
      RNAs distinct from the miRNA precursor. Several lines of evidence suggest that
      miRNAs arose at least twice during eukaryotic evolution from an ancestral, pan
      eukaryotic small RNA producing molecular machinery, though alternative scenarios
      cannot be ruled out. A handful of plant miRNAs are strongly expressed, widely
      conserved among plants, and have identical targets in long-diverged species; most
      of these very well conserved miRNA-target relationships involve DNA-binding
      transcription factors with suspected roles in developmental control. In contrast,
      a much greater number of plant miRNAs are weakly expressed, poorly conserved, and
      have few if any readily identifiable targets. These miRNAs appear to be
      evolutionarily "transient", and many of them may be of little to no selective
      value. However, this ever-changing cast of transient miRNAs could provide a
      reservoir of potentially useful miRNAs from which new regulatory interactions
      sometimes are selected.

PMID- 18342024
TI  - [Cellular strategies in bone tissue engineering: a review].
AB  - The objective of bone tissue engineering is to reconstruct bone stock using
      matrix structures, osteoinductor factors and osteogenic cells. Different types of
      natural or synthetic biomaterials are available or under development. The
      objective of recent work is to optimize matrix materials, particularly with
      better cell adhesion to the surface and better osteoconduction. For
      osteoinductors, most research is currently focused on bone morphogenetic protein
      (BMP) and angiogenic factors such as vascular endothelial growth factor (VEGF).
      Concerning the nature of the cells to be implanted, there is a clear dissociation
      between fundamental and clinical studies. Many clinical studies have demonstrated
      the strong osteogenic potential of fresh harvested total bone marrow. There has
      been nevertheless little fundamental work on the use of total bone marrow as a
      source of cells for bone tissue engineering. Most of the fundamental work has
      been focused on the use of mesenchymatous stromal cells selected from bone marrow
      and cultivated ex vivo. This approach which was first developed more than fifteen
      years ago has shown that the adjunction of these cells can improve the
      osteoformative capacity of bone substitutes. This strategy has, however, had
      almost no clinical impact to date since only two studies involving four patients
      have been reported. The purpose of this article is to review current research
      concerning bone tissue engineering using total bone marrow and mesenchymatous
      stromal cells.

PMID- 18342025
TI  - [Comparative study of the anatomic and clinical effect of Weaver or subtotal
      subscapularis tendon section in Latarjet procedure].
AB  - PURPOSE OF THE STUDY: The aim of this work was to compare the anatomic and
      functional effect on the subscapularis muscle of two ways of sectioning its
      tendon during Latarjet procedure: complete vertical section and Weaver section
      (partial section of the lower third preserving the upper part of the tendon).
      MATERIAL AND METHODS: We compared two series (eight-year interval) of patients
      comparable for age, gender, form of instability, type and level of sports
      activity. Twenty-nine patients underwent complete vertical section (group 1) and
      30 Weaver section (group 2). All were reviewed with minimum four year follow-up.
      The clinical analysis involved strength of internal rotation, the maximal hand
      back distance, and the Constant and Duplay scores. The radiographic analysis was
      coupled with computed tomography in 46 patients (23 in each group). Loss of
      subscapularis muscle thickness compared with the non-operated side was noted as
      was the Bernageau fatty infiltration stage. RESULTS: No recurrent dislocation was
      noted in either group. There were six cases of nonynion in group 1 and seven in
      group 2. The Gerber was positive in five patients in group 1 and zero in group 2
      (P=0.01). Loss of internal rotation strength between the operated and healthy
      side, expressed in percentage, was 48.4% for group 1 and 17.9% for group 2
      (P<0.0006). In group 1, the fatty infiltration stage of the subscapularis muscle
      was: stage 0 (n=3), stage 1 (n=11), stage 2 (n=3), stages 3 and 4 (n=6). In group
      2, these stages were: stage 0 (n=21), stage 1 (n=1), stage 1 (n=2) and zero stage
      3 and 4 (P<0.0001). DISCUSSION: The Latarjet operation remains the reference
      procedure for anterior stabilization of the shoulder joint. The choice of the
      incision technique for the subscapularis muscle tendon remains a subject of
      debate. Recent studies have demonstrated the importance of subscapularis muscle
      trophicity to obtain a good mid- and long-term clinical outcome. We have
      ourselves demonstrated elsewhere that complete section of the subscapularis
      tendon leads to secondary tears and subsequent fatty degeneration. CONCLUSION:
      Our study demonstrates that Weaver section in the Latarjet procedure enables
      placing the bone block in conditions equivalent to those achieved with total
      section while preserving better trophicity of the subscapularis muscle.

PMID- 18342026
TI  - [Traumatic hip dislocations in children].
AB  - PURPOSE OF THE STUDY: Traumatic hip dislocation is a rare event in children.
      Appropriate management remains a subject of debate. The purpose of this study was
      to investigate the epidemiological, therapeutic features of this situation and
      the long-term outcome after treatment. MATERIAL AND METHODS: This was a
      retrospective analysis of 15 traumatic hip dislocations collected over a period
      of 20 years in pediatric patients with at least two years follow-up. We searched
      for predisposing factors and factors affecting prognosis. RESULTS: The series
      included 11 boys and three girls, mean age eight years. Dislocation was posterior
      in 13 hips and anterior in two. Time to reduction was less than 3h in eight
      cases, 3-6h in five and greater than 6h in two. After reduction, traction was
      performed in nine children, for 20 days on average, followed in five cases by
      immobilization for 40 days on average. Five hips were immobilized directly after
      reduction. We identified two groups by age: group 1 with dislocations in children
      aged less than six years (seven children) were characterized by low-energy
      trauma. Dislocation was not associated with other lesions. Predisposing factors
      (overt ligament hyperlaxity, insufficient superolateral head cover, coax valga)
      were noted in six children. Reduction was simple. Later treatment consisted in
      immobilization with a pelvispedious cast for 30-45 days. Group 2 were
      dislocations in children aged over six years (seven children) victims of high
      energy trauma. Associated injuries were frequent. Predisposing factors were not
      present. At mean 11 years follow-up, all hips are considered normal clinically.
      The radiograph was normal for 14 hips. In one case, there was a slight coax
      magna. In three patients, defective femoral head cover persisted. Coxa valga
      persisted in two patients. DISCUSSION: Traumatic dislocation of the hip joint is
      rare in very young children, but results from a minimally traumatic event. This
      suggests the presence of predisposing factors in this category of patients,
      particularly capsuloligamentary hyperlaxity. After reduction, immobilization can
      be recommended. Traumatic hip dislocations in children are different from the
      adult variety due to their rarity, the general absence of associated fractures,
      easy reduction and better prognosis. The epidemiological and therapeutic features
      in children older than six years are however similar to those in adults.

PMID- 18342027
TI  - [Treatment of femoral fracture on previous implants with minimally-invasive
      surgery and total weight-bearing: benefit of locking plate. Preliminary report].
AB  - PURPOSE OF THE STUDY: We report a consecutive prospective series of femoral
      fractures on previous implants. The purpose was to assess treatment with locking
      compression plates and total weight-bearing. MATERIAL AND METHOD: From June 2002
      to December 2005, we treated 21 patients (16 women, five men) for fractures on
      previous implants: total hip arthroplasty (n=11), total knee arthroplasty (n=1),
      unicompartmental prosthesis (n=1), gamma nail (n=4), hip screw (n=1). Mean
      patient age was 75.8 years (range 39-90). Osteosynthesis was performed on an
      orthopedic table or on a standard table using a minimally-invasive approach for
      fixation with a locking compression plate (Synthes) LCP) to bridge the implants
      in place and avoid any zone of weakness. The rehabilitation protocol included
      immediate total weight bearing. RESULTS: At last follow-up there were three
      deaths and one failure so that there were 17 patients with a mean follow-up of
      15.9 months (range 6-45 months). The following outcomes were noted. Minimally
      invasive surgery was used in 18 cases, access to the fracture focus in three.
      Total weight bearing was possible immediately after surgery in 12 patients and
      partial weight bearing (20 kg) for two. There were two infections, two general
      complications and one early displacement. Healing was achieved at 6-10 weeks.
      Misalignment greater than 10 degrees was noted in three cases. DISCUSSION: This
      work illustrates the use of locking plates for minimally-invasive repair of
      fractures on previous implants with total weight bearing. This technique combines
      the principles of closed fixation and preservation of the fracture hematoma with
      material stability. In this form, use developed progressively. It is now common
      practice to use plate fixation for femoral fractures. The LISS system was then
      developed progressively for minimally-invasive repair of distal fractures. We
      widened the concept to include more proximal approaches. The use of the locking
      screws in the plate corresponds to what could be called an internal external
      fixator with three pins (two corresponding to the cortical screws plus the
      plate), which enable a solid fixation. Screw hold seems to be sufficient to allow
      early weight bearing. CONCLUSION: Locking plates have been shown to be an
      effective treatment for femoral fractures on previous implants allowing a stable
      fixation sufficient for early weight bearing.

PMID- 18342028
TI  - [Results of the Evora dual mobility socket: five years follow-up].
AB  - PURPOSE OF THE STUDY: Dislocation is a well-known complication of total hip
      arthroplasty. The risk can be reduced to one or two cases per thousand using a
      double mobility cup. The survival rate achieved with the Bousquet implant is 95%
      at 10 years. The complications with this implant are early mobilization and
      inguinal pain. An overly large cup and insufficient primary and secondary
      fixation can be implicated. The design of the original implant was later modified
      to limit these early complications. The purpose of this work was to check the
      validity of the changes made. PATIENTS AND METHODS: The chromium-cobalt moulded
      cup was used. The outer surface of this cup presents large geometric striations
      and is coated with hydroxyapatite. The cup has the shape of a half sphere of 180
      degrees and a posterior wall prolongation measuring 6.5mm. Three mechanisms were
      used for the primary fixation: an asymmetrical growth ring, four anchorage stems,
      and a superior screw. Two hundred cups were implanted in 194 patients. The
      femoral piece was a Charnley stainless steel implant (n=139), a titanium SEM
      implant (n=59) or another implant (n=12). Cement was used for 193 implantations.
      The series included 97 women and 103 men with osteoarthritis (n=180), necrosis
      (n=16), surgery for fracture and primary arthroplasty (n=9). The Harris and
      Postel-Merle-d'Aubigne scores were noted. Eight radiographic criteria were
      analyzed to assess the position of the cup and the radiological course of the
      interface. RESULTS: Mean time to surgery was six years. Mean age at surgery was
      70 years (range: 32-91) and varied depending on the operators from 67 to 73
      years. At last follow-up: 17 patients had died, eight were lost to follow-up and
      five were bedridden. Three patients underwent revision surgery. Thus, this
      analysis included 170 prostheses followed for more than five years (mean: six
      years, range: 5-7 years). The Harris score improved from 48 to 92 and the Postel
      Merle-d'Aubigne score from 2/5/4 to 5.8/5.9/5.5 (range: 4-6/5-6/1-6). None of the
      patients complained of anterior pain during hip flexion against resistance. Cup
      inclination was 46 degrees on average (range: 62-22 degrees ). Medialization,
      lateralization or ascension greater than 10mm of the centre of rotation was not
      observed on the postoperative films. At last follow-up, no measurable
      mobilization or migration could be identified on plain X-rays. Lucent lines,
      condensations and bony defects around the cup, when visible postoperatively, were
      not found on the last follow-up X-rays. There were two cemented femoral pieces,
      which developed a lucent line in the nonspecific metaphyseal area. There were no
      cases of granuloma and no cam effect. Three patients underwent revision for
      femoral loosening, fracture of the femur below the prosthesis, and hematogenous
      infection. There were no cases of dislocation. DISCUSSION: Changing the design of
      the implant to modify its volume, material and primary fixation has eliminated
      the early mobilizations and inguinal pain described for the original Bousquet
      cup. These options have not had any deleterious effect on prosthesis stability.
      The question of long-term wear remains an important problem and requires
      optimization: a neck as thin as possible, optimized surfacing, elimination of
      laser marks, extraction leads, head skirts.

PMID- 18342029
TI  - [Survival of dual mobility socket with a mean 17 years follow-up].
AB  - PURPOSE OF THE STUDY: Within the framework of the 2007 symposium of the French
      Hip and Knee Society devoted to the dual mobility socket, we report a
      retrospective multicentric series of 438 first-intention total hip prostheses
      with a dual mobile socket at 17 years mean follow-up. The purpose of our report
      was to ascertain the 15-year survival and analyze failures. MATERIAL AND METHODS:
      The series included 438 first-intention prostheses. This was a homogeneous
      multicentric series. Sockets were: 80 Novae-1 titanium Serf cups and 358 Novae-1
      stainless steel Serf cups. All stems were inserted without cement: 185 Pf)
      stainless steel screwed Serf stems, 228 PRO titanium screwed Serf stems, 25
      Corail stems. The mobile polyethylene insert was retaining. All of the heads were
      22.2mm chromium-cobalt heads. Degenerative hip disease was the main etiology and
      mean follow-up was 17.18 years (range: 12-20). Mean age at implantation was 54.8
      years (range: 23-87). The actuarial method with 95% interval of confidence was
      used to determine the 15-year cup survival. RESULTS: At last follow-up, none of
      the patients had presented an episode of early or late instability. Analysis of
      the socket at last follow-up showed: 13 aseptic loosenings, 23 intraprosthetic
      dislocations, and seven replacements of the polyethylene insert for wear. The
      overall 15-year prosthesis survival was 89.2+/-8.7%. The overall 15-year socket
      survival was 96.3+/-3.7%. DISCUSSION: The fact that at last follow-up none of the
      implants had exhibited instability confirms the long-term stability of the dual
      mobility socket. The results in terms of 15-year survival confirm earlier
      reports. The main cause of failure was cup fixation, which is the weak point of
      this technique with the initial Novae cup, which did not have hydroxyapatite
      coating. The second leading cause was intraprosthetic dislocation, which can be
      divided into three main categories. The first is intraprosthetic dislocation in a
      context of pure wear with normal function of the dual mobility; the retaining
      feature of the insert looses its efficacy due to wear. The second category is
      intraprosthetic dislocation in a context of cup loosening with a third-body
      effect and increased retention wear, in which case we consider that the cup
      loosening is the primary event leading to secondary rapid wear and subsequent
      intraprosthetic dislocation. The third category is intraprosthetic dislocation
      cause by a cam effect in a context of fibrosis or impingement involving a large
      calcification. We have had only two femoral failures by aseptic loosening, most
      certainly related to use of noncemented implants, which limits the extension of
      granulomas to the polyethylene. Studying more specifically the three series from
      Saint-Etienne where three different configurations were used, it would appear
      that the titanium cup has a better survival and that the titanium used for the
      thinner necks would be an unfavorable factor for intraprosthetic dislocation.

PMID- 18342030
TI  - [Acute hematogenous osteomyelitis of the neck of the femur in children: 28
      cases].
AB  - PURPOSE OF THE STUDY: Osteomyelitis of the neck of the femur is uncommon, often
      with a misleading clinical presentation. We report a series of 28 cases of
      osteomyelitis of the femoral neck to illustrate the particular clinical and
      imaging findings related to this localization. MATERIAL AND METHODS: This was a
      series of 28 children treated in our unit from 1990 through 2004: 17 boys and 11
      girls, mean age eight years (range one month to 14 years). We analyzed the data
      in this series using a standard checklist, which noted the diagnostic and
      therapeutic measures. Results were analyzed by studying the complications,
      anatomic and functional outcome at mean follow-up of 3.5 years. RESULTS: Time
      from symptom onset to consultation was five days on average with a delay of 4.5
      days from consultation to hospitalization. Intense pain was noted for eight
      patients (28%) and total functional incapacity of the limb was noted for 15
      (53%). Hip stiffness was observed in 11 patients (39%). The diagnosis of
      osteomyelitis of the femoral neck was established on the basis of imaging (MRI or
      scintigraphy) in three patients with bacteriological proof in two, of operative
      findings which confirmed the neck localization in 19, and on changes in the X-ray
      image of the neck in six. A positive bacteriology was noted in 71%. The germ was
      isolated from blood cultures and local samples obtained by arthrotomy in five
      patients (same germ), only in blood cultures for four, and only in local samples
      in 11. Met-S Staphylococcus aureus was isolated in 18 patients, Met-R S. aureus
      in one and a Streptococcus in one. All patients were given medical treatment and
      25 underwent surgery. There were five thromboembolic complications and five
      patients who developed femoral pandiaphysitis. Results were analyzed at mean 3.5
      years (range four months to 14 years). Complete hip motion was recovered in 78%.
      There were four cases of hip stiffness and two cases of ankylosis. Partial
      cephalic necrosis was noted in two hips and total necrosis of the head and neck
      in two. DISCUSSION: Little data is available in the literature on isolated
      osteomyelitis of the femoral neck. Based on the pathogenic mechanisms known for
      osteomyelitis, an isolated localization in the neck of the femur, with no other
      site in the hip joint, is quite possible in an early stage of infection. We
      discuss the specific clinical and imaging features of this localization. Analysis
      of our findings show that the prognosis of femoral neck osteomyelitis is directly
      related to time to management. Outcome is poorer when treatment is started late.
      Prognosis is poor if pandiaphysitis develops.

PMID- 18342031
TI  - [Hip septic arthritis in young children with sickle-cell disease].
AB  - PURPOSE OF THE STUDY: Sickle-cell anemia is an inherited disorder exposing
      patients to diverse complications, particularly bone and joint disease. Septic
      arthritis of the hip joint is a frequent infection in sickle-cell anemia. Without
      early management, there is an important risk of invalidating hip dysfunction. The
      purpose of this study was to analyze the epidemiological, clinical and
      therapeutic aspects of septic arthritis of the hip joint in order to focus on the
      need for early diagnosis, the best way to improve the prognosis of hip function.
      MATERIAL AND METHODS: This was a retrospective study over a 10 year period (1987
      1996) which included nine children (seven boys and two girls), mean age six years
      who were managed in our hospital for septic arthritis of the hip joint. These
      children had at least one hemoglobin S: phenotypes SS (n=5), SC (n=2), AS (n=2).
      RESULTS: In these sickle-cell anemia children, the septic arthritis developed in
      a non traumatic context with osteonecrosis of the femoral head. One hip was
      involved in six children and both in three (12 hips). Mean time from symptom
      onset to consultation was eight days. Salmonella sp. were identified in nine hips
      (including all of the bilateral cases) and Staphylococcus sp. in three. The
      treatment included antibiotics for six weeks, puncture-drainage, and
      immobilization for three to four weeks. Outcome was excellent in nine hips and
      good in three. DISCUSSION: The diagnosis of septic arthritis of the hip joint
      must be made early, based on ultrasound or scintigraphic findings.
      Bacteriological samples of joint fluids are required to adjust the antibiotic
      regimen. Salmonella sp. were the most common agents in our patients, but other
      series have reported Klebsiella pneumoniae and Staphylococcus or Pneumococcus sp.
      Drainage is preferred, if possible by arthroscopy. Arthrotomy should be reserved
      for cases with a thick discharge which is difficult to evacuate via puncture
      drainage. Early diagnosis, careful evacuation of the joint collection, and
      adapted antibiotic therapy with hip immobilization are the keys to good
      functional outcome.

PMID- 18342032
TI  - [Pigmented villonodular synovitis in children: review of six cases].
AB  - PURPOSE OF THE STUDY: Pigmented villonodular synovitis is an exceptional
      condition in children. The clinical, biological and imaging presentation is not
      specific and a histology sample is required for certain diagnosis. Because of
      this lack of specificity, together with the rare occurrence of the disease, late
      diagnosis is not uncommon, making correct management an even greater challenge in
      the growing child. MATERIAL AND METHOD: Between 1995 and 2001, six children were
      treated for pigmentary villonodular synovitis, four girls and two boys, mean age
      11.5 years. The knee was involved in five cases (three diffuse forms and two
      localized forms). One diffuse form involved the ankle. The diagnosis was
      suggested by the MRI findings in all patients and confirmed at the histological
      examination of a biopsy sample. Surgery was used in five cases and medical
      treatment in one patient with a diffuse form affecting the knee. A synoviorthesis
      (Hexatrione) was used systematically in three diffuse forms affecting the knee
      joint. RESULTS: Mean follow-up was 58 months. Recurrence was noted in two diffuse
      forms, one involving the knee at 10 months from arthroscopic synovectomy and one
      involving the ankle 24 months after surgical synovectomy. Systematic use of the
      synoviorthesis did not prevent recurrence in one case. The synoviorthesis was
      also used in the two cases of recurrence as a complement to surgical treatment
      but with no effect. Growth was not affected in any of the children. DISCUSSION:
      The etiopathogenic mechanism underpinning pigmented villonodular synovitis
      remains unclear. Genetic factors are suspected in childhood cases. MRI is the
      complementary examination of choice for diagnosis and follow-up. In children,
      treatment of pigmented villonodular synovitis depends on marginal excision of the
      lesion for localized forms and total synovectomy for the diffuse forms. The
      efficacy of the triamcinolone hexacetonide synoviorthesis remains open to debate
      and would require a larger series with longer follow-up for evaluation.

PMID- 18342033
TI  - [Arthroscopic tightening of the anterior cruciate ligament].
AB  - We present here the preliminary results obtained with arthroscopic tightening of
      the anterior cruciate ligament. Six patients underwent the technique. Four had
      had prior ligamentoplasty, two had sequelae of tibial spine fractures. Laxity
      persisted in all cases. The transplant or the ligament were continuous and
      insertion points were well-positioned. The procedure consisted in using a
      trephine to bore the tibial bone at the "foot" of the ligament or transplant in
      order to tighten the ligament. There was no evidence of instability after the
      arthroscopic tightening procedure. Mean pre- and postoperative differential
      anterior drawer values were successively 9.2 and 3.9 mm. For native or
      reconstructed anterior cruciate ligaments, which are continuous and well
      positioned but not loose, arthroscopic tightening spares the need for ligament
      transplant and appears to be free of specific morbidity.

PMID- 18342034
TI  - [Original vacuum dressing for the treatment of open femur fracture with gangrene
      immobilized by external fixation].
AB  - We report a case of gangrene, which developed following an open fracture of the
      femur immobilized with an external fixator in a 45-year-old patient. A
      conventional vacuum dressing (VAC Therapy) could not be applied with the external
      fixator in place. An original vacuum dressing was thus fashioned after surgical
      debridement. Scabs were covered with calcium alginate. The lower limb was
      enveloped in sterile dressings and vacuum was achieved by suction with gastric
      tubes under adhesive films. The dressing was redone every 48 h in a surgical
      setting. Antibiotic prophylaxis enabled cure of the infection. Budding appeared
      within two weeks enabling skin grafting. Centro-medullary nailing was undertaken
      on day 30 to accelerate bone healing. At three months from the trauma, the
      initial loss of sensitivity in the leg and foot noted at the first weight bearing
      required programmed disarticulation of the knee after femur and wound healing. At
      six months, the patient had resumed his occupational activities and was pain
      free. This type of dressing could be useful for tissue loss over a fracture
      immobilized with an external fixator. This type of assembly can easily be
      installed in the operating room.

PMID- 18342035
TI  - [Bilateral congenital fusion of the scaphoid and the trapezium. A case report].
AB  - Congenital synostosis has been described between nearly all of the carpal bones.
      It can occur in an isolated form or most commonly in relation between the lunatum
      and the triquetrum. It can also occur in a multiple form and be associated with
      other malformations. We report a rare case of scaphoid-trapezium fusion observed
      bilaterally in a nearly asymptomatic 63-year-old patient.

PMID- 18342036
TI  - [Thirty-four years follow-up of a bilateral Mac Kee-Farrar arthroplasty without
      loosening or osteolysis].
AB  - We report the case of a 93-year-old patient with bilateral Mac Kee-Farrar hip
      arthroplasties implanted 34 years ago. The patient was seen in 2005 for a type B1
      periprosthetic fracture on the right prosthesis implanted in 1973. There was no
      loosening and the fracture was treated by plate fixation. Before the fracture,
      the Postel-Merle d'Aubigne (PMA) score was 16 on both sides, with a Devane
      activity score grade 2. At last follow-up, the PMA score was 13 for both hips,
      with a Devane activity score grade 1. Serum cobalt level was 1.36 microg/L
      (normal <1 microg/L). This exceptional case is to our knowledge the longest
      observed with this implant without clinical or radiographic signs of loosening.
      The serum cobalt level, rarely assayed after more than 30 years, was within the
      limits accepted for a metal-on-metal hip bilateral arthroplasty. We discuss the
      causes of failure and success of the Mac Kee-Farrar implant as reported in the
      literature and remark that long survival of the metal-on-metal bearing can
      occasionally be observed without signs of wear. Recent works on the metal-on
      metal bearing merit attention.

PMID- 18342037
TI  - [Sclerosing epithelioid fibrosarcoma. A case report].
AB  - Sclerosing epithelioid fibrosarcoma is a rare variant of fibrosarcomas, which was
      recently identified as a separate entity due to specific histologic and
      immunohistochemistry features and its poor prognosis. We report a case of
      sclerosing epithelioid fibrosarcoma of soft tissues, which developed in a 37-year
      old woman who presented a tumor involving the posteromedial aspect of the left
      knee and which progressed in size for one year. Imaging revealed a well-delimited
      tumor process measuring 8 cm in its largest diameter and situated in the medial
      compartment of the left knee. Histology of the tumorectomy specimen and the
      immunohistochemistry study led to the diagnosis of sclerosing epithelioid
      fibrosarcoma of soft tissues. This new case illustrates the characteristic
      features of this tumor and recalls the difficult pathological diagnosis.

PMID- 18342038
TI  - [Osteoid osteoma of the talus and simple bone cyst of the homolateral calcaneus.
      A rare association].
AB  - Osteoid osteoma and simple bone cyst are readily observed in long bones, but are
      much less common in the short bones of the foot. The association of these two
      tumors in the same foot is exceptional. We report the case of a 15-year-old girl
      who presented an osteoid osteoma of the talus and a simple bone cyst of the
      calcaneus of the left foot. The patient complained of pain in the rear foot for
      four months which worsened at night and was of the inflammatory type. The
      physical examination was normal. Standard x-rays revealed a simple bone cyst in
      the calcaneus which could not explain the nighttime inflammatory pain.
      Scintigraphy and computed tomography of the left foot revealed an osteoid oseoma
      of the talus. Biopsy total resection of the osteoid osteoma with curettage and
      filling with cancellous bone of the simple bone cyst were performed. The patient
      has been free of recurrence at three years follow-up.

PMID- 18342053
TI  - [Myoclonus and epilepsy: diagnosis and pathophysiology].
AB  - Myoclonus presents as a sudden brief involuntary jerk triggered by the central
      nervous system. Electromyographic studies enable determining whether the jerk is
      caused by a muscular contraction, i.e. positive myoclonus, or by an interruption
      of muscular activity, i.e. negative myoclonus. Many classifications have been
      proposed, reflecting our lack of understanding about myoclonus. Myoclonus is a
      symptom and should never be considered as a diagnosis. Clinical history and
      physical examination are the basis to diagnosis. Clinical neurophysiology testing
      can reveal a neuroanatomical localization and certain patterns have some
      etiological specificity. Etiological hypotheses can be put forward on the basis
      of clinical and neurophysiological data. The cortex is the most commonly
      identified source of myoclonus, but the subcortical area and spinal area can also
      be involved. Myoclonus is considered epileptic when it is combined with an
      epileptiform discharge on the EEG. The International Classification of Epileptic
      Syndromes should be applied in this situation. Myoclonic epilepsies are a
      collection of syndromes in which myoclonic seizures are a prominent feature.
      Myoclonus can occur as one among several seizure components, as the only
      manifestation of seizure, or as one of multiple seizure types within an epileptic
      syndrome. Neurophysiological studies are needed to investigate the
      pathophysiological mechanisms of the myoclonus. Electrophysiological studies
      report that myoclonic seizures are produced through a cortical generator via a
      polysynaptic mechanism acting on muscles. Apparently, the epileptiform discharges
      stimulate the motor cortex resulting in myoclonus jerk. Despite recent progress,
      advances are still needed to achieve a better understanding of the
      pathophysiological mechanisms involved in myoclonus. In myoclonic epileptic
      syndromes, more useful information can probably be obtained from studies grouping
      several patients with a same epileptic syndrome than from single case reports.

PMID- 18342054
TI  - [Hereditary ataxias, spastic parapareses and neuropathies in Eastern Canada].
AB  - It has been demonstrated, for many inherited diseases, that historical events
      have shaped the various regional gene pools of Eastern Canada. In so doing, it
      has given rise to the increased prevalence of some rare diseases due, to founder
      effects. The following neurogenetic disorders were first identified in patients
      from Eastern Canada: AOA-2, Arsacs, HSN-2, Arca-1, HMSN/ACC and Arsal. The
      population of Eastern Canada, we are convinced, will still allow the
      identification of new rare forms of hereditary ataxias, spastic parapareses and
      neuropathies as well as contribute to the uncovering of their mutated genes. We
      have summarized our current knowledge of the various hereditary ataxias, spastic
      parapareses and neuropathies in Eastern Canada. The study of the more common and
      homogenous features of these diseases has been largely completed.

PMID- 18342055
TI  - [Update on vascular dementias].
AB  - The concept of vascular dementia greatly evolved since Hachinski's description of
      multi-infarct dementia. Vascular dementias are reviewed with emphasis on current
      diagnostic criteria, elusive natural history, neuroradiological aspects,
      difficult epidemiological features and intriguing links with Alzheimer's disease.
      The recent proposed shift from vascular dementias to a broader definition of
      "vascular cognitive disorders", including non demented subjects with "vascular
      cognitive impairment", is described, followed by a brief review of current
      treatments.

PMID- 18342056
TI  - [Bilateral papilledema: prospective study of fifty patients].
AB  - In this prospective study, we report fifty consecutive cases of bilateral
      papilledema without neurosurgical or obvious ophthalmologic etiology, referred to
      our institution between January 2005 and March 2007. Lumbar puncture with opening
      CSF pressure measurement distinguished two groups of patients: Group 1 (n=39)
      with and Group 2 (n=11) without intracranial hypertension. In Group 1, 9/39
      patients presented secondary intracranial hypertension mainly due to cerebral
      venous thrombosis. In 30 patients, after complete investigations, a diagnosis of
      idiopathic intracranial hypertension was made: as commonly reported, patients
      were predominantly overweight (96.7% with body mass index>25kg/m2) young (mean
      age=27.6 years) and women (96.7%). Eleven patients with intracranial hypertension
      had no headaches. In Group 2, the most common diagnosis was bilateral non
      arteritic anterior ischemic optic neuropathy, but rare causes have been
      identified.

PMID- 18342057
TI  - [Cognitive impact of mitoxantrone and methylprednisolone in multiple sclerosis:
      an open label study].
AB  - Interferons beta have shown some positive effects on cognitive function in
      multiple sclerosis (MS). The potential immunosuppressive impact of mitoxantrone
      on cognitive dysfunction in MS has never been evaluated. We assessed changes in
      cognitive dysfunction in patients with very active MS treated with mitoxantrone
      combined with methylprednisolone. We assessed a non randomized controlled trial
      including successively 15 consecutive MS patients. Very active MS was defined by
      a progression of at least two EDSS points or more than two relapses during the
      previous year and at least one enhanced lesion after gadolinium infusion on MRI.
      All patients received a monthly intravenous pulse of mitoxantrone (20mg) for six
      months with methylprednisolone (1g). Global cognitive efficiency, memory and
      executive function were assessed before treatment (M0) and after six months (M6)
      and 12 months (M12) of treatment. To evaluate the learning effect, 15 healthy
      subjects also participated. A significant improvement in global cognitive
      efficiency was observed at M6 and was sustained at M12, as a few parameters on
      memory and executive functions. We suggest that mitoxantrone combined with
      methylprednisolone has a potential positive effect on cognitive functions.

PMID- 18342058
TI  - [Dystonia, tremor and repetitive instrumental use].
AB  - Three characteristic observations are presented along with three tables
      presenting 24 patients with the following elements in common: excessively
      repeated use of an instrument such as a pen, a musical instrument or a tool. The
      appearance after that use of a central pathological phenomenon that includes a
      local dystonia of a hand or the mouth, a tremor, or the association of a tremor
      and a dystonia, all within the muscular domain corresponding to that of the use.
      The discussion, which is based exclusively on the clinical findings, deals with
      the following elements: the role of the use of the instrument rather than task
      itself, the predominant pathogenic factor which is the repetitive action, to
      which is added a genetic component in one incompletely penetrant case of DYT 1,
      and a probable genetic susceptibility in the others. The absence of improvement
      with rest distinguishes this central pathology from rheumatologic or orthopaedic
      problems involving repetitive activities. The evolution is slowly declining when
      the responsible action is continued. This occurs in three stages: a specific
      disorder involving only the use of the particular instrument, a more enlarged
      involvement affecting other activities and eventually a dystonia associated with
      a tremor or a postural tremor always located to the initial area. The therapeutic
      interventions suggested by the pathologic role of the repetitive movement is: (1)
      to advise a new training for the instrument that excludes the habitual movement;
      (2) to advise the patient to vary any newly acquired repetitive movements.

PMID- 18342059
TI  - [Cerebral vasculitis with aneurysms caused by varicella-zoster virus infection
      during AIDS: a new clinicoangiographical syndrome].
AB  - We describe three cases of cerebral angiopathy with aneurysms caused by a
      meningeal varicella-zoster virus infection occurring during AIDS. The clinical
      picture was rather stereotyped: severe immunocompromission due to HIV infection,
      ongoing multifocal cerebrovascular disease with territorial infarcts, lymphocytic
      meningitis with normal glucose content (two cases) or hypoglycorrhachia (one
      case), multifocal cerebral vasculopathy with narrowings and aneurysms, healing
      with or without neurological sequelae after intravenous aciclovir treatment. The
      diagnosis of varicella-zoster virus-induced angiopathy was ascertained by the
      positive specific PCR in the CSF in the three cases and by the results of the
      cerebromeningeal biopsy in one case. Although, varicella-zoster virus is already
      known as a cause of cerebral angiopathy both in the immunocompetent and the
      immunocompromised, these three cases are the first ever described of a particular
      angiopathy with narrowings and ectasias complicating AIDS. The infectious
      treatable cause and the risk of aggravation without treatment require early
      active oriented investigations in case of a patient with cerebrovascular disease
      occurring during HIV infection, including a CSF study with varicella-zoster PCR,
      to allow specific antiviral treatment. In our three cases, aciclovir intravenous
      treatment (30mg/kg per day) enabled VZ virus clearing from the CSF and stopped
      the course of the vasculopathy.

PMID- 18342060
TI  - [Lambert-Eaton Myasthenic Syndrome associated with vocal cord carcinoma].
AB  - INTRODUCTION: Lambert-Eaton Myasthenic Syndrome (LEMS) is an autoimmune
      channelopathy in which patients produce autoantibodies directed against voltage
      gated calcium channels. LEMS is paraneoplastic in 50% of patients, most
      frequently associated with small cell lung carcinoma. We describe a case of
      paraneoplastic LEMS associated with a vocal cord carcinoma. OBSERVATION: A 64
      year-old man developed in five months muscle weakness affecting gait. Clinical
      examination showed proximal muscular deficiency, areflexia and dysphonia.
      Electrophysiologic study showed potentiation greater than 500% after post
      exercise facilitation and 76 percent increment response at high-rate repetitive
      nerve stimulation (20Hz). Diagnosis of LEMS was confirmed by electrophysiologic
      study and anti-voltage gated calcium channel antibodies (90pM, positive value
      greater or equal to 70pM). Left vocal cord lesion histology showed epidermoid
      carcinoma. A combination of vocal cord tumor removal by endoscopy and treatment
      by pyridostigmine, 3-4 diaminopyridine and intravenous human immunoglobulin
      improved neurological symptoms. CONCLUSION: Paraneoplastic syndromes in
      association with cancers of the larynx and hypopharynx are unusual. Only two
      cases are reported with LEMS associated with larynx carcinoma. We describe an
      unusual case of LEMS associated with a left vocal cord carcinoma.

PMID- 18342061
TI  - [Post-traumatic tarsal tunnel syndrome: interest of muscular MRI].
AB  - INTRODUCTION: Tarsal tunnel syndrome is a compressive neuropathy of the tibial
      nerve with multiple causes. This syndrome is difficult to diagnose and can be
      missed because of its subjective symptomatology. OBSERVATION: In our patient,
      suspected post-traumatic tarsal tunnel syndrome was confirmed at MRI. This case
      highlights muscle signal anomalies caused by their denervation in the tibial
      nerve territory. CONCLUSION: MRI can provide supplementary information to the
      electromyography (EMG) and contribute to positive and etiologic diagnosis of
      peripheral nerve lesions.

PMID- 18342062
TI  - [Cervicobrachial neuralgia revealing neurosarcoma].
AB  - Malignant peripheral nerve sheath tumor (MPNST) or neurofibrosarcoma, previously
      described as malignant Schwannoma or neurosarcoma, is an extremely rare cause of
      malignancy localized in the neck. Half of reported cases occurred in patients
      with neurofibromatosis in Von Recklinghausen disease type I. Typical features
      include high grade malignancy and a tendency to recurrence and distant
      metastases. We report the case of a 56-year-old woman with neurosarcoma of the
      neck, which was revealed by a cervicobrachial neuralgia. The physical examination
      found a mass on the left side of the neck. Plain radiographs showed
      osteoarthritis. MRI showed a well-defined paravertebral mass. Pathologic
      diagnosis was neurosarcoma. Radiotherapy was delivered.

PMID- 18342063
TI  - [Abstracts of the 8th Annual Meeting of the French Neurology Society, 17-18
      January 2008, Paris, France].

PMID- 18342066
TI  - [Questioning the role of systemic corticosteroids and urticaria].

PMID- 18342067
TI  - [Acne and diet].

PMID- 18342068
TI  - [Antibiotic susceptibility of Staphylococcus aureus strains responsible for
      community-acquired skin infections].
AB  - BACKGROUND: The appearance and worldwide spread of community-acquired methicillin
      resistant Staphylococcus aureus (MRSA) skin infections warrant new studies of
      antibiotic resistance among strains of S. aureus responsible for cutaneous
      infections seen in general practice. PATIENTS AND METHODS: A prospective,
      multicentre study was performed from December 2003 to August 2004 in outpatients
      of both sexes presenting with a common bacterial skin infection presumed due to
      S. aureus (primary or secondary impetigo, ecthyma, paronychia, folliculitis,
      furunculosis). The investigators (n=50) were GPs from seven French regions.
      Clinical data (history, previous hospitalisation, type of infection, site,
      previous treatment, etc.) were collected using a standard questionnaire. A
      bacteriological sample was taken in attempt to isolate S. aureus after which
      antibiograms were prepared and minimal inhibiting concentrations determined (11
      antibiotics). RESULTS: Four hundred and eighty patients of mean age 42 years
      (range: 2-94 years) were included. S. aureus was isolated from cultures in 205 of
      477 samples, i.e. in 197 patients (eight had two strains of S. aureus). Patients
      with S. aureus had a primary skin infection in 104/197 cases (53%) (24 impetigo,
      20 paronychia, 45 folliculitis or furunculosis) and a secondary infection in
      93/197 cases (47%), with 4.9% patients being hospitalized within the preceding
      six months (median: 10 days). Percentages of resistant S. aureus strains were as
      follows: penicillin: 86%, erythromycin: 32%, ciprofloxacin: 9.3%, tetracycline:
      5.8%, oxacillin: 5.8% (representing MRSA strains), fusidic acid: 4.4%,
      clindamycin: 3.4%, mupirocin: 1% and gentamicin: 0.5%. All S. aureus strains were
      sensitive to vancomycin and rifampicin. Except for one strain also resistant to
      tetracycline and fusidic acid, all MRSA strains were also resistant to
      ciprofloxacin. DISCUSSION: Multiresistant bacterial strains could become a
      concern in the community in France in the near future. In our study, only 14/197
      (6.8%) S. aureus strains were sensitive to all tested antibiotics, whereas 21/197
      (10.7%) were resistant to at least three of them. Compared to a French study
      performed in private practice in 2000, the level of MRSA is growing only slowly
      (5.8% versus 3.9%), whereas the percentage of strains of Peni-R/Oxa-S S. aureus
      are stable (80.5%). CONCLUSION: Common bacterial infections of the skin due to
      MRSA or to multiresistant S. aureus are not rare in France and have tended to
      increase slowly in recent years.

PMID- 18342069
TI  - [Impact of corticosteroid withdrawal in chronic urticaria: a prospective study of
      17 patients].
AB  - BACKGROUND: Although two reports have indicated benefits of oral steroids in
      acute urticaria, the 2003 French guidelines emphasized their inefficacy in the
      treatment of idiopathic chronic urticaria, and the lack of studies. We present
      the results of a prospective study in 17 patients presenting severe chronic
      urticaria who agreed to stop taking oral steroids over a one-year period.
      PATIENTS AND METHODS: This single-centre prospective study included adults (1)
      presenting chronic urticaria as defined by the French consensus conference
      committee on chronic urticaria (2003), (2) exhibiting at least two of the
      following three criteria: sleep disturbance due to itching, repeated angioedema,
      general symptoms; (3) unresponsive or mildly improved by antihistaminic (anti-H1)
      therapy; (4) receiving oral steroids at least three days per month. After
      inclusion in the study, oral steroids were stopped either immediately or
      gradually, on a case-by-case basis. Two different anti-H1 agents were prescribed
      at inclusion with follow-up visits two, four and 12 months after complete
      withdrawal of oral steroids. RESULTS: Seventeen patients were included (M/F sex
      ratio: 0.54; mean age: 40 years). General signs (fever, arthralgia, various
      pains), delayed pressure urticaria, and idiopathic cutaneous vasculitis were
      noted respectively, in seven, nine and three cases. Oral steroids had been taken
      for three to 30 days per month before inclusion. Three patients had received
      prior treatment (e.g., immunosuppressants), with no improvement. After withdrawal
      of oral steroids, (1) 47% of patients presented a short relapse and/or worsening
      of chronic urticaria, (2) three patients dropped out of the study at four months
      (persistence of chronic urticaria unacceptable to patients, despite a clinical
      score showing mild response), (3) six (35%) had complete remission of chronic
      urticaria at 12 months, with delayed pressure urticaria in three of these cases,
      (4) eight (47%) had partial remission, five of whom had delayed pressure
      urticaria, (5) lasting remission of general symptoms. DISCUSSION: Our study shows
      that most cases of chronic urticaria are managed without oral steroids since
      inefficacy of anti-H1 drugs is generally only temporary. After withdrawal of oral
      steroids, a short increase in chronic urticaria was frequently observed with
      constant remission from extracutaneous signs and/or histological evidence of
      vasculitis. We suggest an active role of oral steroids in the failure of anti-H1
      therapy. Moreover, oral steroids do not seem to confer any benefits in delayed
      pressure urticaria, and pending further prospective controlled studies, we
      recommend that these drugs be prescribed sparingly in chronic urticaria.

PMID- 18342070
TI  - [Acne, pregnant women and zinc salts: a literature review].
AB  - BACKGROUND: Acne in adult women is a common reason for dermatological
      consultation. Dermatologists are occasionally confronted with the problem of
      treating acne in women who are either pregnant or seeking to become pregnant, or
      in breast-feeding women, in whom zinc salts are the only form of systemic
      treatment that may be envisaged. PATIENTS AND METHODS: The purpose of our study
      was to provide an overview of existing data concerning the use of the zinc salts
      in pregnant and breast-feeding women based on a literature review, a survey of
      prescription of zinc gluconate by French dermatologists, and finally, analysis of
      French pharmacovigilance data. RESULTS: There are many studies involving the use
      of zinc supplements during pregnancy. In these studies, more than 2500 pregnant
      women were given zinc at different doses. None of these studies described any
      abnormalities, congenital malformation, harmful effects or risk for the foetus
      associated with the use of zinc during pregnancy at doses below 75 mg/day.
      Although there are fewer studies of the use of zinc supplements in breast-feeding
      women, no abnormalities associated with use of zinc during breast-feeding have
      been reported. According to the results of the prescription survey, around 10,000
      pregnant women and 2000 breast-feeding women are treated each year for acne using
      zinc gluconate, with only four serious adverse events involving zinc being
      reported since the initial introduction of the product, and with zinc having a
      doubtful causal relationship. DISCUSSION: Zinc plays a key role in our body's
      physiology, since it is involved in the activities of many enzymes. In addition,
      zinc requirements increase during pregnancy, mainly because of its utilisation
      during embryogenesis and fetal development. This literature review shows that use
      of zinc salts in pregnant women is beneficial in those with zinc deficiency but
      that it has no harmful effects in those without zinc deficiency.

PMID- 18342071
TI  - [Genetics of skin barrier impairment in atopic dermatitis].

PMID- 18342072
TI  - [Interstitial granulomatous dermatitis with arthritis: four cases].
AB  - BACKGROUND: Interstitial granulomatous dermatitis with arthritis, or Ackerman's
      syndrome, is characterized by inflammatory articular flares of potentially
      destructive outcome and cutaneous lesions of varied patterns: cord-like lesions
      on the flanks or violaceous plaques on the trunk and limbs. Histologically, the
      main features are histiocytes laminated between collagen fibres, sometimes
      organized in rosettes comprising tiny granulomas surrounding fibres of
      homogeneous aspect. CASE REPORTS: Four patients fitting this description were
      investigated. Cutaneous lesions displayed various patterns: cord-like lesions
      (one patient), brown plaques on the flanks edged with papules (one patient),
      grossly annular violaceous plaques on the back (one patient), and infiltrated
      plaques on the palms and thighs (one patient). Joint symptoms were present in all
      cases (one seropositive rheumatoid arthritis and one seronegative rheumatoid
      arthritis, both already known; acute rheumatoid arthritis in two cases). The
      histological pattern was quite similar in all cases, with laminated histiocytes
      in palisading layers mixed with swollen collagen fibres; "rosette" figures were
      present in two cases. Autoimmune response was seen with antinuclear antibodies
      (two cases) and/or rheumatoid factor (two cases). The short-term outcome of
      cutaneous lesions was rapidly favourable in most cases with systemic steroids
      (one case) or Non Steroidal Anti-Inflammatory Drugs (one case), and spontaneously
      in one case. COMMENTS: This entity, defined by the presence of inflammatory
      arthritis and cutaneous lesions of various clinical types, either more specific
      but infrequent (cord-like), or less specific but more frequent (plaque-like), and
      featuring a peculiar histological pattern, chiefly affects women aged between 30
      and 80 years. Pathophysiological mechanisms and nosological borders are debatable
      and authors consider this condition as either an autonomous disease or else a
      mere subset of vasculitis with palisading granulomas in collagen vascular
      disorders, despite the rarity of authentic vasculitis. A setting of autoimmunity
      is frequently present. Furthermore, a fairly similar histological pattern is
      sometimes seen in some lesions forming a subset of cutaneous side-effects of
      drugs. Articular outcome may be unfavourable with joint destruction in more than
      half of patients, whether or not in a setting of rheumatoid arthritis.
      Spontaneous resorption can occur. Treatment has not yet been codified and is
      based primarily on anti-inflammatory drugs.

PMID- 18342073
TI  - [Pseudo-Kaposi's sarcoma secondary to superficial arteriovenous malformation:
      Stewart-Bluefarb syndrome].
AB  - BACKGROUND: Pseudo-Kaposi's sarcoma or Stewart-Bluefarb subtype
      acroangiodermatitis is uncommon and is caused by arteriovenous fistula and
      malformation. We report a new case. CASE REPORT: A 33-year-old man presented with
      painful red-violet plaque on the dorsum of the toes with angiomatous nodules on
      the sole. Histological and immunohistochemical studies for CD34 were consistent
      with Kaposi's sarcoma. Doppler ultrasonography and femoral angiography showed
      multiple distal arteriovenous shunts. Free-flow embolisation with fragments of
      Ethibloc gelatin sponge was performed and arteriography, performed immediately
      afterwards, showed delayed venous drainage. The outcome was good with complete
      drainage of the angiomatous lesions. DISCUSSION: Pseudo-Kaposi's sarcoma Stewart
      Bluefarb subtype begins early in life in male subjects, with unilateral skin
      lesions. It bears clinical and histological resemblance to Kaposi's sarcoma.
      Doppler ultrasonography and angiography show arteriovenous fistulas that
      classically develop at shunts, explaining the role of traumatism and high
      vascular pressure in the genesis of this disease.

PMID- 18342074
TI  - [Melanoma in invisible naevus spilus].
AB  - BACKGROUND: Diagnosis of naevus lesions may be complex where they contain little
      or no pigmentation. Naevus spilus (or naevus on naevus) is, generally, readily
      identified by the difference in pigmentation between overlying and underlying
      naevi and healthy skin. Malignant transformation of naevus spilus is rare. We
      report two cases of melanoma in which surgical procedures revealed underlying
      melanocyte lesions, diagnosed at histology but undetectable on clinical
      examination. PATIENTS AND METHODS: Two patients were operated for melanoma in
      which surgery, at a site remote from the melanoma, suggested incomplete relapse
      despite the fact that previous clinical examination had indicated healthy skin. A
      diagnosis was made of melanoma in invisible naevus spilus. DISCUSSION: Diagnosis
      of melanoma in invisible naevus spilus may be suspected where several naevi are
      found together in a specific area. The main problem is the therapeutic stance to
      be adopted since complete excision of the underlying naevi is difficult in
      practice. Wood's light examination may be helpful.

PMID- 18342075
TI  - [Infantile fibrosarcoma mimicking rapidly involuting congenital haemangioma
      (RICH)].
AB  - BACKGROUND: While haemangioma is common, an unusual appearance or course should
      alert the clinician's concern. Congenital haemangioma, particularly rapidly
      involuting congenital haemangioma (RICH), may carry a risk of misdiagnosis as
      congenital malignant tumours such as infantile fibrosarcoma (also known as
      congenital infantile fibrosarcoma). In this case, histological diagnosis may
      prove inconclusive, as in the case reported herein. PATIENTS AND METHODS: At
      birth, a newborn baby presented angiomatous lesions on the sole of the left foot
      that was initially considered as congenital haemangioma. Histopathological
      examination suggested highly remodelled immature infantile haemangioma. After
      surgery, the tumour increased in size within eight weeks. Reanalysis of the
      histology slides resulted in a diagnosis of infantile fibrosarcoma. This
      diagnosis was confirmed by the presence of a specific translocation seen in
      infantile fibrosarcoma (ETV6/NTRK3). CONCLUSION: There is a risk of erroneous
      diagnosis in newborn infants between angiomatous tumour in RICH and malignant
      congenital tumours (particularly infantile fibrosarcoma). Clinicians should be
      attentive for this type of lesion and take all necessary diagnostic measures.

PMID- 18342076
TI  - [Cyclosporine-induced follicular eruption].
AB  - BACKGROUND: Cyclosporine is one of the immunosuppressant agents most widely used
      in the prevention and treatment of organ transplant rejection and also in
      autoimmune diseases. Many cutaneous side effects have been described with oral
      cyclosporine, mainly in transplant recipients, for example, hypertrichosis,
      gingival hyperplasia and viral skin infections. Here, we report an unusual
      follicular eruption induced by this drug. PATIENTS AND METHODS: A 22-year-old man
      presenting cystic fibrosis received a double-lung graft in January 2005. Six
      weeks later, he developed a subacute eruption of follicular papules, not highly
      pruritic, located mainly on the trunk, the extensor surfaces of the limbs and the
      face. Diagnosis of cyclosporine-induced follicular eruption was adopted on the
      basis of the histological and microbiological findings. Complete regression was
      obtained after switching to tacrolimus. DISCUSSION: Three similar cases were
      previously reported characterized by typical follicular changes different from
      those observed in hypertrichosis or pilar keratosis. This rare cutaneous side
      effect may be explained by the direct action of cyclosporine on the pilosebaceous
      unit: this drug is known to extend the anagen phase of the follicular cycle and
      to induce toxic follicular dystrophy at higher tissue concentrations. This
      particular toxicity is usually seen after many months of treatment. In our
      patient, the time to onset was shorter, probably due to occasionally excessive
      plasma concentrations.

PMID- 18342077
TI  - [Sporotrichoid cutaneous leishmaniasis in Tunisia: a clinical and histological
      study].
AB  - BACKGROUND: The sporotrichoid variety of cutaneous leishmaniasis is defined by
      the presence of dermal and hypodermal nodules along the lymphatic stream, and
      remote from the primary inoculation lesions. This clinical form is usually
      considered rare. The aim of our study was to investigate the epidemiological,
      clinical, histological and evolutionary particularities of sporotrichoid
      cutaneous leishmaniasis in the south of Tunisia. PATIENTS AND METHODS: During a
      systematic study of all cases of cutaneous leishmaniasis from the south of
      Tunisia diagnosed in our hospital in 2002, sporotrichoid forms were diagnosed on
      the basis of clinical criteria. In all cases of sporotrichoid cutaneous
      leishmaniasis, the principal clinical characters were systematically specified.
      Cutaneous biopsies of subcutaneous nodules were performed in six cases. RESULTS:
      Of 102 patients with cutaneous leishmaniasis, 19 presented sporotrichoid
      cutaneous leishmaniasis, that is, a frequency of 19%. Between two and 20 painless
      subcutaneous nodules were arranged in linear strings on the upper leg in 79% of
      cases. Time to appearance varied between 12 days and one year after the primary
      lesions. Fourteen appeared without any preliminary treatment for cutaneous
      leishmaniasis and five appeared after Glucantime infiltration in the primary
      lesions. Biopsies of the nodules showed an inflammatory infiltrate composed of
      lymphocytes and histiocytes. This infiltrate was particularly dense and rich in
      plasmocytes at the level of the deep dermis. The biopsies were deep enough to
      involve the hypoderm in one case and the same type of infiltrate was noted at the
      level of interlobular septa. A small number amastigotes was seen in one deep
      biopsy sample. Outcome was favourable in all cases under treatment. CONCLUSION:
      Sporotrichoid cutaneous leishmaniasis appears to be common in the south of
      Tunisia, were cutaneous leishmaniasis is dominant because of Leishmania major. It
      is not associated with a poor prognosis.

PMID- 18342078
TI  - [Crusted scabies at the spinal injury site of a paraplegic man].

PMID- 18342079
TI  - [Tunisian pemphigus foliaceus with antidesmoglein 3 antibody].

PMID- 18342080
TI  - [Cutaneous schistosomiasis: six cases].

PMID- 18342081
TI  - [Diffuse papular lesions].

PMID- 18342082
TI  - [Keratitis-ichthyosis-deafness (KID) syndrome].

PMID- 18342083
TI  - [Lichen planus].

PMID- 18342084
TI  - [Missense mutations in the BCS1L gene in Bjornstad syndrome].

PMID- 18342085
TI  - [Adult-onset xanthelasmoid mastocytosis].

PMID- 18342086
TI  - [Contact allergy with tacrolimus then pimecrolimus].

PMID- 18342087
TI  - [Extent of lymph node clearance required in stage III-B melanoma].

PMID- 18342088
TI  - [Actinic keratoses are still actinic keratoses].

PMID- 18342089
TI  - [Ocular malignancies of xeroderma pigmentosum: clinical and therapeutic
      features].
AB  - BACKGROUND: Our aim was to determine the epidemiological, clinical and
      histopathological features as well as the most suitable therapeutic management of
      malignant ocular tumours in xeroderma pigmentosum based on a retrospective study
      of 32 patients. PATIENTS AND METHODS: Our study was conducted in the
      ophthalmology unit of the Charles-Nicolle hospital between January 2001 and
      January 2004. A complete bilateral ophthalmologic investigation was performed for
      all patients and the severity of photophobia was scored on a four-point scale.
      RESULTS: Thirty-two xeroderma pigmentosum patients were examined during this
      period. Photophobia was found in 66% of cases and 19 of 32 patients (59%) were
      presenting ocular and periocular malignancies. The mean age of patients was 19
      years (four to 40 years). Thirty-three tumours were diagnosed in these 19
      patients. Blindness was noted in 3/26 (12%) eyes in patients without malignant
      tumour and in 10/38 (26%) eyes in patients with malignant tumour. CONCLUSION:
      Various types of malignant ocular-cutaneous tumours relating to sunlight
      developed in xeroderma pigmentosum patients. These disorders are more prevalent
      in severe and moderate forms of xeroderma pigmentosum. Lesions occur almost
      exclusively in the eyelids, conjunctiva, limbus and/or cornea. The rapid
      regression of these tumours, particularly in the cornea and limbus, may cause
      blindness, emphasising the importance of early management and regular monitoring
      of patients in order to allow early diagnosis of this condition, thereby ensuring
      the least mutilant treatment possible.

PMID- 18342090
TI  - [The value of allergy survey in a retrospective series of 40 patients with
      burning-mouth syndrome (stomatodynia)].
AB  - BACKGROUND: By definition, stomatodynia or burning-mouth syndrome involves oral
      pain with no causes being found on history taking or examination. An allergic
      origin is often suspected by doctors and patients alike. In this study, we
      attempted to assess the value of epicutaneous tests in demonstrating allergic
      causes for patients presenting stomatodynia. PATIENTS AND METHODS: This was a
      single-centre retrospective study of patients undergoing epicutaneous tests
      between 1996 and 2003 to screen for allergic causes of mouth pain not accounted
      for by any abnormalities seen during examination performed at consultations for
      mouth disease. RESULTS: Forty patients were included (11 male, 29 female; mean
      age: 58 years), and 39 were excluded. Sixteen patients presented at least one
      positive test, with a total of 35 positive tests in all. In decreasing order of
      frequency, the causes were metals, mercury derivatives (nickel salts: n=5; chrome
      salts: n=3; palladium salts: n=2; phenylmercuric acetate: n=2; thiomersal: n=2;
      cobalt salts: n=1; gold salts: n=1; mercury: n=1) and resins (acrylates: n=4).
      The relevance of these test results was considered probable in three cases and
      possible in five cases, associated with the existence of metals or resins in
      patients' mouths. The Peru balm test was positive in four cases but was not
      relevant. Tests for personal products were negative in all cases, with the
      exception of one case of resin from a prosthesis and one case of tixocortol
      pivalate. COMMENTS: Type I stomatodynia (daily occurrence with gradually increase
      in discomfort throughout the day) and type II stomatodynia (permanent) are not
      normally attributable to allergies. However, for type III stomatodynia (non
      permanent, with acute episodes followed by remission), an allergy survey guided
      by questioning may be undertaken to determine the cause, primarily prostheses or
      diet. The relevance of positive test results must be interpreted with caution in
      view of the incidence of positive epicutaneous tests for metals and Peru balm
      among the general population studied.

PMID- 18342091
TI  - [Chromomycosis in Guadeloupe].
AB  - BACKGROUND: Chromomycosis is a widespread subcutaneous fungal infection seen
      essentially in tropical and subtropical regions and transmitted via skin injury
      caused by the prickles of plants or infected wood splinters. It is prevalent
      throughout the West Indies including Guadeloupe, where its incidence is not well
      known. PATIENTS AND METHODS: This retrospective and descriptive study concerns
      five histologically established cases of chromomycosis in Guadeloupe between 1995
      and 2005. The five patients were diagnosed and treated at Pointe-a-Pitre
      University Teaching Hospital. RESULTS: The study concerned four male patients and
      one female patient with an average age of 78 years; four were from the Basse
      Terre district and one was from the Grande-Terre district. The most frequent
      clinical aspect was nodular or verrucous. The most common initial topography was
      the upper limbs. Fonsecaea pedrosoi was the only species identified. Diagnosis
      was confirmed by histopathology, which in all cases revealed sclerotic cells.
      Three patients underwent surgical treatment and two received medical treatment;
      only two patients were cured by 2005. DISCUSSION: Our study confirms the presence
      of a source of chromomycosis in Guadeloupe, where Fonsecaea pedrosoi is clearly
      the best adapted species. It also highlights the difficulties of therapeutic care
      in tropical areas.

PMID- 18342092
TI  - [Reticulated telangiectasic erythema following morphine pump implantation].
AB  - BACKGROUND: Reticulated telangiectasic erythema is a cutaneous complication
      reported after in the implementation of pacemakers and cardiac defibrillators.
      Here we report a case occurring after the implantation of a morphine pump.
      PATIENTS AND METHODS: Reticulated and pigmented telangiectasic erythema was
      observed at the morphine pump implantation site in a 56-year-old man presenting
      chronic lower back pain. DISCUSSION: To date, cutaneous telangiectasic erythema
      has been reported following implantation of cardiac defibrillators and pacemakers
      although the physiopathogenesis of the condition is poorly understood. An
      identical case was recently described following implantation of morphine pump, as
      in our case. We discuss hypotheses concerning the possible physiopathogenesis of
      such lesions.

PMID- 18342093
TI  - [AA amyloidosis: a little-known complication of chronic leg ulcer].
AB  - INTRODUCTION: AA amyloidosis, secondary to inflammatory chronic diseases like
      rheumatoid arthritis, is often complicated by renal failure. Chronic inflammatory
      dermatoses constitute rare causes of AA amyloidosis. CASE-REPORT: We describe two
      cases of AA amyloidosis discovered after renal failure in patients presenting leg
      ulcers for several years. AL amyloidosis was suspected in both cases because of a
      history of monoclonal gammopathy in one patient and of plasmocytoma in the other.
      The diagnosis of AA amyloidosis was confirmed on renal histology through the
      detection of AA antibodies in amyloid deposits. No extrarenal amyloidosis was
      seen in either patient and there were no inflammatory diseases other than chronic
      leg ulcers. DISCUSSION: AA amyloidosis is caused by serum amyloid protein A
      (SAA), a reactive inflammatory protein. AA amyloidosis is thus caused by chronic
      inflammatory diseases, but only rarely by cutaneous inflammatory diseases. To our
      knowledge, the literature contains only seven other published cases of AA
      amyloidosis secondary to chronic leg ulcers. A review of the literature does not
      indicate whether cure of ulcers has any effect on the accompanying renal failure.
      We imagine that AA amyloidosis secondary to leg ulcer is in fact under-diagnosed.
      However, since the first specific treatment for AA amyloidosis is currently being
      evaluated by the Food and Drug Administration, it is essential that this serious
      complication of chronic leg ulcers be widely recognised.

PMID- 18342094
TI  - [Disseminated cutaneous leishmaniasis secondary to lymphoedema: two cases].
AB  - BACKGROUND: Dissemination of cutaneous leishmaniasis may take various forms:
      satellite papules, sporotrichoid nodules and widespread papulonodular lesions
      (disseminated cutaneous leishmaniasis). We describe a particular clinical form of
      dissemination in two patients with erysipelas secondary to lymphoedema. PATIENTS
      AND METHODS: Case 1. A 75-year-old man with diabetes consulted for erysipelas of
      the leg secondary to lymphoedema. The site of entry was an infected cutaneous
      leishmaniasis lesion. The initial outcome was favourable under intravenous
      penicillin G treatment. Twelve days later, some fifty papulonodular lesions
      appeared and were strictly limited to the erythematous erysipelas plaque. PCR
      screening of papulonodular lesion smears for Leishman bodies was positive.
      Histological examination of skin biopsy samples showed lobular panniculitis. Case
      2. A 64-year-old woman with diabetes presented erysipelas in the right upper limb
      secondary to lymphoedema scattered with multiple erythematous, infiltrated,
      papular lesions in a setting of cutaneous leishmaniasis lesions. PCR analysis of
      smears taken from the secondary nodular lesions demonstrated the presence of
      leishmaniasis, while histological analysis of biopsy samples revealed
      panniculitis. DISCUSSION: Disseminated cutaneous leishmaniasis is characterized
      by the appearance of multiple (>10) pleomorphic lesions on two or more
      noncontiguous areas of the body. Our two patients presented certain features of
      disseminated cutaneous leishmaniasis. However, they were unusual in terms of the
      strict localisation of nodular lesions to the erysipelas plaque. This particular
      aspect suggests haemolymphatic dissemination of the protozoan infection from the
      initial lesion as a result of local factors.

PMID- 18342095
TI  - [Contiguous cutaneous inflammation].
AB  - BACKGROUND: Contiguous cutaneous inflammation is a circumscribed inflammatory
      reaction of the skin overlying a pathological process affecting an adjacent deep
      seated anatomical structure. Contiguous cutaneous inflammation can sometimes
      reveal serious internal diseases. Through a case report and a literature review,
      we characterize the concept of contiguous cutaneous inflammation. CASE REPORT: A
      77-year-old woman with a past medical history of rhinorrhoea and chronic headache
      was admitted for a verrucous and erythematous lesion on her right cheek, evolving
      for two months with incomplete remission after numerous antibiotics.
      Histopathological examination was inconclusive. Facial CT revealed pansinusitis.
      Diagnosis of contiguous cutaneous inflammation to sinusitis was retained.
      Complete healing of cutaneous lesions was observed after surgical treatment of
      the sinusitis. DISCUSSION: Contiguous cutaneous inflammation is characterized by
      localization over the causal disease, parallel evolution with the latter and the
      absence of clinicopathological specificity. The underlying pathological process
      is variable and may be tumoral or infectious, or simply the presence of an
      internal device. Migration of inflammatory cells and/or diffusion of mediators in
      a localized skin area could be involved in pathogenesis.

PMID- 18342096
TI  - [Nicorandil-induced cutaneous ulceration on a pacemaker implantation wound].
AB  - BACKGROUND: Nicorandil is a potassium-channel activator used to prevent angina.
      While mucosal ulceration is a well-known adverse effect of this drug, skin ulcers
      have been described only rarely, and always in association with mucosal ulcers.
      PATIENTS AND METHODS: An 86-year-old woman presented ulceration on a pacemaker
      implantation scar despite complete initial wound healing. Nicorandil had been
      initiated three months earlier. None of the usual causes of ulceration of a
      pacemaker scar were seen. Complete and permanent wound-healing was achieved 12
      days after discontinuation of nicorandil. DISCUSSION: This is the first reported
      case of cutaneous ulceration on a vulnerable area of skin ascribable to high-dose
      nicorandil.

PMID- 18342097
TI  - [Tobacco contact dermatitis caused by sensitivity to sorbic acid].
AB  - BACKGROUND: Contact dermatitis caused by tobacco is rare and poorly understood.
      In this paper, we report what is to our knowledge, the first case of tobacco
      contact dermatitis with identification of the causative agent. PATIENTS AND
      METHODS: A 46-year-old man was hospitalised for diffuse dermatitis originating in
      the left leg. Subsequent epicutaneous tests indicated that this dermatitis was
      ascribable to sensitisation to the sorbic acid present in Fucidin cream applied
      around a chronic wound. A persistent plaque of eczema observed on the day of
      examination opposite the patient's right trouser pocket suggested the implication
      of tobacco powder with which the pocket was soiled. An epicutaneous test using
      tobacco (moistened in water) proved positive (++ at 48 and 72 h). This tobacco
      contained sorbic acid, used as a preservative. DISCUSSION: The positive test for
      sorbic acid was relevant not only regarding the lesions on the patient's legs
      (application of a topical cream containing sorbic acid) but also for the lesion
      on the patient's thigh and for palmar dyshidrosis (through contact with strands
      of loose rolling tobacco). To our knowledge, this is the first recorded case of
      contact dermatitis caused by sorbic acid in tobacco.

PMID- 18342098
TI  - [Do emollients prevent active episodes of atopic dermatitis?].

PMID- 18342099
TI  - [DRESS syndrome with severe pulmonary involvement following oral intake of a
      homeopathic drug].

PMID- 18342100
TI  - [Study of variations between surgeons regarding inguinal lymph node clearance in
      melanoma].

PMID- 18342101
TI  - [Bullous eruption on the hands of a 34-year-old woman].

PMID- 18342102
TI  - [Cutaneous side effects of sorafenib and sunitinib].

PMID- 18342103
TI  - [Dermoscopic diagnosis of scabies].

PMID- 18342104
TI  - [Phototoprotection: a new classification of sun protection products].

PMID- 18342105
TI  - [Cutaneous dirofilariosis].

PMID- 18342106
TI  - [Pseudoxanthoma elasticum with cutis laxa and multiple coagulation factor
      deficiency: a single genetic entity].

PMID- 18342107
TI  - [Phtiriasis palpebrarum in an infant].

PMID- 18342108
TI  - [Three diseases heralded by glossitis].

PMID- 18342109
TI  - [Adverse effects of Cimicifuga].

PMID- 18342110
TI  - [Radiation induced skin reactions].
AB  - Radiotherapy is one of the most important treatment modality of cancers. Skin
      secondary effects are well known. Cutaneous complications are described.
      Physiopathogenic mechanisms are reported. Many preventative and treatment options
      have been used with varying degrees of evidence of success. Information of
      patients, further research studies and a multidisciplinary approach are necessary
      to increase the management of radiation induced skin reactions.

PMID- 18342111
TI  - [Interest of a sterilised anti-burning gel in radiation dermatitis: results of a
      comparative study].
AB  - Trial objectives were to assess effectiveness and tolerance of sterilized Avene
      thermal spring water anti burning gel (ATSW gel) in prevention of radiation
      dermatitis in adults irradiated (6 weeks) for breast (n=61) or head and neck
      (n=8) cancer. Patients included in this open labelled, 2 parallel groups,
      multicentric study, were randomly assigned to apply five times daily for ten
      weeks either the Avene spring water gel (n=35) or trolamine cream (n=34). The
      median of emergence of the first objective radiation dermatitis signs was 31 days
      in the ATSW gel group and 29 days in the control group (p=0,924). The median
      incidence for pruritus in patients of the ETA gel group was 46 days versus 27
      days (p=0,028) and 44 days versus 24 days for pain (p=0,426). Global efficacy was
      <<very good>> in 46,7 % of patients of the ETA gel group versus 17,2 % (p=0,029)
      and tolerance was <<very good>> in 65,5 % of the ETA gel group versus 40,7 %
      (p=0,107). No radionecrosis was observed. In conclusion, the efficacy of the
      Avene spring water gel was similar to the control product in prophylaxis of
      radiation dermatitis. Tolerance was better and the pruritus was significantly
      more delayed in patients who applied the Avene spring water gel than in controls.

PMID- 18342112
TI  - [Tolerance of the association sucralfate / Cu-Zn salts in radiation dermatitis].
AB  - The aim of this study was to evaluate the tolerance of topical application of the
      combination sucralfate / copper zinc salts in radiation dermatitis in women
      suffering from breast cancer and treated by radiotherapy. 47 patients (average
      age : 57,5 years) that have to be treated by radiation therapy on non lesional
      areas, were included into this open multicentric study. They had to apply
      Cicalfate cream twice a day, from the fi rst radiation therapy session and during
      10 weeks. Patients were treated by photon- or electrontherapy (72 % et 28 %,
      respectively; cumulated total dose : 58,6Gy). Tolerance was considered to be
      excellent. The radiation dermatitis (score NCIC > or = 2) was noted at the 3rd
      week of radiotherapy only in 5 % of the subjects and in 53 % of the subjects, the
      last week of treatment. Pruritus was significantly increased at D21. Pain and
      discomfort were increased at D28, but remained low intensity. The soothing effect
      of the combination of sucralfate/ copper zinc salts were considered satisfying or
      very satisfying by investigators and patients during the study, varying from 94
      to 100 % of satisfaction. The impact of radiation therapy on the patients'quality
      of life, assessed by DLQI, evaluated at the end of the study was not
      statistically different from the score calculated at D7 (DLQI=0,8 et D7 versus
      DLQI=1 at D70). Thus, topical application of the combination sucralfate / copper
      zinc salts can be used in the indication radiation dermatitis.

PMID- 18342113
TI  - [Cutaneous side effects associated with epidermal growth factor receptor and
      tyrosine kinase inhibitors].
AB  - Basic knowledge in oncogenesis has dramatically improved in the last decade
      providing more recently new drugs for cancer treatment. These new targeted
      compounds usually act by inhibiting tyrosine kinase activity of one or more than
      one proteins involved in tumor growth and cancer progression. This
      pharmacological effect is the result of monoclonal or small molecule action. Many
      of these new compounds have cutaneus secondary effects. Cancer patients are now
      facing new toxicity, essentially skin toxicity. The cutaneous side effects
      observed in the patients depend on the drug. For example, EGFR inhibitors induce
      acneiform rash whereas multitarget tyrosine kinase inhibitors induce different
      more complex effects which physiopatholgy is not yet completely understood. The
      secondary effects that are frequently observed are described is this article. A
      better clinical long term management of these effects is a clear medical need as
      of these effects could be surrogate markers of drug efficacy.

PMID- 18342114
TI  - [Medical corrective make-up in post- chemotherapy].
AB  - INTRODUCTION: Medical corrective make up can be applied to hide the adverse
      effects of cancer treatments. The aim of this study was to evaluate the tolerance
      and the satisfaction of patients needing medical make up to hide the cutaneous
      side effects induced by chimiotherapy and to improve self-esteem. METHODS: 90
      cancer patients were included in this multicentric study. They were being treated
      by chimiotherapy and had eyebrow alopecia, complexion changes, irregular lip
      contour or lip dryness. They were made up by socio-esthecians. Photos were taken
      before and after applications of make up. The patients had to fill in a self
      questionnaire at home. The duration of the study varied from 1 to 4 weeks.
      RESULTS: Included patients were 52 years old. Tolerance was considered to be
      satisfactory or very satisfactory by 95,4% and 98,9% of the patients for eyebrow
      pencil corrector and the dual lip and contour corrector, respectively. Questions
      on quality of live and self-esteem revealed that the medical corrective make up
      improved the quality of life in general for 81,2% of the patients. This product
      range enhanced the self-esteem of 76,8% of the patients. Cosmetic agreement was
      highly satisfactory. CONCLUSION: In this study in which patients were suffering
      from cancer and treated by chimiotherapy, we showed that medical corrective make
      up can improve the quality of life with a very good tolerance.

PMID- 18342116
TI  - [Esthetic dermatology].

PMID- 18342117
TI  - [Anatomy, immunology of skin and cutaneous annexes].
AB  - The aim of this paper, is to bring to the young dermatologists, the basic
      knowledges in the fields of anatomy, immunology and physiology of the skin which
      are necessary to know, for starting aesthetic dermatology with a sufficient
      security for the patient.

PMID- 18342118
TI  - [Normal and abnormal human skin colour: from research to aesthetics].
AB  - Skin color is controlled by pigmentary genes that regulate constitutive skin
      pigmentation and by environmental factors, the most obvious of them being solar
      U.V. At this time, more than 125 distinct pigmentary genes are known. They affect
      embryogenesis and survival of the melanocyte system, melanosome biogenesis,
      melanogenesis, melanosome transport and transfer, eumelanins/pheomelanins ratio
      and epidermal melanosome turn-over and elimination. The pigmentary disorders of
      the skin are common and represent an important part of dermatologist activity.
      They concern at the same time the general dermatology and the aesthetic
      dermatology.

PMID- 18342119
TI  - [Skin aging: clinicopathological features and mechanisms].
AB  - Skin aging various considerably between individuals and depends on intrinsic
      factors such as age, oestrogen deficiency during menopause, and on extrinsic
      factors such as exposure to UV light and tobacco addiction. The clinical and
      histological characteristics of these different types of aging are described as
      well as the principle highly complex mechanisms that are involved. Treatment for
      skin aging has become the main reason why patients consult in cosmetic
      dermatology. For this reason, dermatologist should know how to analyse this
      condition and offer suitable therapeutic care that takes into account the aging
      of the subcutaneous tissue.

PMID- 18342120
TI  - [Subcutaneous tissue: anatomy and aging].
AB  - A deep understanding of the soft tissue from the face and his aging is necessary
      when dealing with facial volume injections.

PMID- 18342121
TI  - [Soft-tissue fillers].
AB  - Injections of soft-tissue fillers have rapidly become accessible and essential.
      When dealing with facial aging, it is logical to compensate for the loss of
      volume, but the optimisation of a younger face involves a 3D strategy as well.

PMID- 18342122
TI  - [Injection of resorbable materials].
AB  - Resorbable filling materials are currently the safest products available. The
      side effects with this type of material are few compared to the number of
      patients treated. We can therefore suggest materials that have maximum safety to
      our patients, particularly in cosmetic indications.

PMID- 18342123
TI  - [Adverse reactions to injectable fillers].
AB  - The number of "fillers" grows constantly and allows responding to an ever larger
      demand with mostly hyaluronic acid or collagen based products. However, products
      degrading more slowly, containing polylactic acid or bioactive ceramics. All
      these products bring in general satisfactory results. Their short term tolerance
      shows few side effects, benign and always reversible. Long term, foreign body
      granulomas are very rare if interrogation prior to patient's treatment is
      exhaustive. On the reverse, non degradable products are at the origin of
      unaesthetic and invalidating granulomas, often very delayed and resisting to
      various local treatments. For this reason, these products should not be used
      anymore or only very exceptionally, for soft tissue augmentation.

PMID- 18342124
TI  - [Botulinum toxin A in the treatment of the wrinkles in the upper third of the
      face].
AB  - The practice of botulinum toxin injections is unavoidable in the correction of
      facial aging. In effect botulinum toxin allows to erase dynamic wrinkles, by
      transient and reversible muscular relaxation. This is the best wrinkle treatment
      for the upper part of the face: glabellar lines, horizontal forehead lines and
      crow's feet. This technique requires a good understanding of facial muscular
      anatomy, in order to correctly apply the basics of injection. Every patient is
      unique and only a big experience will allow to refine and personalise injections.

PMID- 18342125
TI  - [Superficial peelings].
AB  - Superficial peels treat frequent skin diseases. Procedures are standardized if we
      respect them. Maintenance program at home is useful to optimize the result. To
      learn how to proceed is easy: it's an ambulatory procedure easy to perform in the
      office of the dermatologist.

PMID- 18342126
TI  - [Theory of lasers and lamps].
AB  - Lasers emit a coherent and monochromatic light beam, whereas pulsed lights
      produce a polychromatic light whose bandwidth is selected by adapted filters. The
      skin's chromophores are made up of water, hemoglobin, and melanin, to which must
      be added the exogenous pigments of tattoos. Each chromophore has its specific
      absorption spectrum. Lasers' main mechanisms of action are the photothermal
      effect and the photomechanical effect.

PMID- 18342127
TI  - [Ablative and fractional lasers].
AB  - The use of pulsed or scanning Carbon Dioxide, and pulsed Erbium-YAG lasers allows
      the programmable and reproducible photocoagulation of thin layers of the
      epidermis and superficial dermis. Thermal damage depends on the type of laser and
      is greater with CO(2) lasers. The degree of neocollagenesis is proportional to
      the thermal damage and is better with CO(2) lasers. Their main indication is the
      correction of photoaged facial skin but they can also be used for corrective
      dermatology, e.g. for scars and genodermatosis. Results are highly satisfactory
      but the technique is invasive and the patient experiences a social hindrance of
      around two weeks. The fractional techniques such as Fraxel are used to treat non
      adjacent microzones without ablation of the epidermis. Around 25 p. 100 of the
      affected region is treated per session without ablation of the epidermis. Each
      fraction is only mini-invasive and is performed under local anesthesia. Social
      hindrance is minimal. Nonetheless, the results are inferior to those obtained
      with ablative lasers, especially regarding deep wrinkles. The treatment is costly
      and four sessions are usually required to treat the whole affected area. Others
      regions of the face may also be treated. Encouraging results have been obtained
      with melasma.

PMID- 18342128
TI  - [Vascular lasers].
AB  - After reviewing the main technical features of the lasers and flashlamps
      currently available, the indications for these devices are detailed, mainly port
      wine stains, facial telangiectasia, hemangiomas, and lower-limb varicosities.
      Respecting the principles of treatment (briefly reviewed herein), contributes to
      preventing complications, which are consequently becoming rare.

PMID- 18342129
TI  - [Laser hair removal].
AB  - The theory behind laser hair removal and pulsed flashlamps is briefly reviewed,
      as are the devices currently available for this indication. Today, the treatment
      procedure has been firmly established so that clear and precise information can
      be provided to patient on the results obtained with these techniques, both for
      medical and esthetic indications. The potential complications are discussed with
      respect to the treatment procedures and a thorough understanding of the
      theoretical foundations.

PMID- 18342130
TI  - [Pigmentary lasers and other polychromatic implements].
AB  - Since the beginning of the 21st century, lasers and flashlamps have replaced
      liquid nitrogen and peelings for depigmentation. They target either endogenous or
      exogenous hyperpigmentation from melanin and tattoo pigments, respectively.
      Ideally, specific QS laser is used, which explodes the target by energy
      confinement with a minimum of side effects. The new fractional lasers, although
      less specific, nevertheless seem promising, notably in melasma, which is not an
      indication for QS laser. Flashlamps, with a broader spectrum, are sometimes
      preferred in certain indications such as Erythrosis coli. The choice of the
      treatment parameters is made based on the type and depth of the pigmentation but
      also the patient's skin phototype.

PMID- 18342131
TI  - [Cosmetic camouflage for a better quality of life].
AB  - Cosmetic camouflage improves the quality of life of our patients without
      interfering with the treatment. This fact has been confirmed by many
      publications. However do we, dermatologists, talk enough about quality of life
      with our patients? The use of camouflage must be included in our medical
      prescription for patients with disfiguring skin diseases.

PMID- 18342132
TI  - [Cosmetics in skin aging].
AB  - Regarding the new active substance proposed to fight against skin-aging, is it
      possible to talk about cosmetic revolution? According to the first definition, a
      revolution is a regular movement that brings an object at its initial place. If
      we look up the pharaonic period, for instance, we realize that we haven't
      invented much. This definition is really far away from the actual meaning of the
      word: a movement that changes the data and deviates from its initial point. We
      finally have two opposite values: a return to the past and a new beginning; we
      could say a change in continuity. This last definition seems to match with the
      aging cosmetology which benefits today from means of modern investigations to
      show some of its effects determined clinically and which registers very broadly
      in a worry of health and ease for each of us.

PMID- 18342133
TI  - [Vigilance in aesthetic dermatology].
AB  - As the acts in aesthetic dermatology are medical acts, they are under vigilance,
      i.e. the indesirable effects have to be declared to structures which centralize
      them for analysing their imputability. VigiDEC have been created by the gDEC, to
      be one of these structures: its objective is confraternal. A precise report of
      the act when it is make, allows to make a right declaration of the unwanted
      effect using the VigiDEC file.

PMID- 18342134
TI  - [Legal guidelines in aesthetic dermatology].
AB  - In cosmetic dermatology where treatment is not subject to a therapeutic need, the
      legal framework must be closely respected. For example, it is essential not to
      undertake procedures that go beyond the scope of one's training, an insurance
      policy is mandatory, and the patient's fully informed consent must be obtained.
      Information must be clear, objective and understandable to the patient, so
      discussion with him/her is of paramount importance. Fact sheets are useful but
      are not to be used instead of discussion. The patient should receive an estimate
      and be given two weeks t think things over before giving his/her informed
      consent. In the event of the patient filing a complaint, it is up to the
      clinician to prove that the patient received adequate information, hence the
      importance of keeping all documentary evidence such as an updated medical file
      and copies of all correspondence. The estimate must be signed by the patient but
      not the fact sheets, contrary to what has come to be common practice in some
      institutions. Insurance companies need a document signed by the patient. This may
      be a pre-printed form stating that the patient has been fully informed by the
      clinician and has given his//her informed consent to the planned procedure.

PMID- 18342135
TI  - [Aesthetic consultation within the activity of the dermatologist].
AB  - Cosmetic and corrective dermatology is a fully fledged field within dermatology
      that should be treated with the same scientific rigor as any other field in
      dermatology. To adapt to growing patient demand, the dermatologist should develop
      particular skills in communication and management in addition to specific medical
      skills.

PMID- 18342136
TI  - [Aesthetic and Corrective Dermatology. Proceedings of the meeting of the
      Aesthetic and Corrective Academy of Dermatology, Nantes, France, 18-20 October
      2007].

PMID- 18342137
TI  - Comparing the CNS morphology and immunobiology of different EAE models in C57BL/6
      mice - a step towards understanding the complexity of multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic neurodegenerative disease that causes
      central nervous system (CNS) inflammation and demyelination, affecting
      approximately two million people worldwide. In humans, different subtypes of the
      disease have been noted, characterized by distinct clinical courses and different
      histopathological manifestations. These disease variants likely result from the
      targeting of different neuroantigens in the CNS and possibly from the involvement
      of different effector arms of the immune system such as CD4(+) and CD8(+) T cells
      as well as autoantibodies. Mechanistic studies addressing the pathomechanisms of
      MS involve experimental autoimmune encephalomyelitis (EAE) in which immunization
      with neuroantigens is used to elicit the disease. Mechanism-oriented studies of
      EAE rely mostly on gene-modified mice on the C57BL/6 (B6) background. Here, we
      discuss how a systematic immuno- and histopathological comparison of the
      presently available EAE models on the B6 background, i.e. myelin basic protein
      proteolipid protein (MBP-PLP) fusion protein (MP4)-, myelin oligodendrocyte
      glycoprotein (MOG) peptide 35-55- and PLP peptide 178-191-induced EAE, can
      facilitate our understanding of the complexity of MS. We point out how the
      development of further models on this basis can help cover the plethora of
      disease manifestations seen in MS.

PMID- 18342138
TI  - The dissection course - necessary and indispensable for teaching anatomy to
      medical students.
AB  - Anatomy is a major basic subject in medicine and related biomedical sciences. A
      central tool most universities use for teaching anatomy is the "dissection
      course", in which medical students learn the basic constructional principles of
      the human body by dissecting a cadaver. In recent years, the relevance and value
      of the dissection laboratory have been under discussion at different universities
      due to high costs and problems of shortness in time in some medical curricula.
      Indeed, during the last 10 years, several universities in the US and the UK have
      abandoned dissection and have moved from a cadaver-oriented to a cadaverless
      anatomy. This development results in a fundamental discussion on the role of the
      "dissection course" in the medical curriculum, ultimately raising the question as
      to whether we should continue teaching anatomy by dissection. This article
      presents nine arguments for the dissection course as a central tool for teaching
      macroscopic anatomy and is an attestment to the continuation of the use of
      cadaver material in anatomical laboratories within the auspices of scholastic and
      university order for the benefit of future physicians with due respect and honour
      guaranteed for every donor.

PMID- 18342139
TI  - Body Worlds: looking back and looking ahead.
AB  - After 10 years of intensive debate about Gunther von Hagens' "Body Worlds"
      exhibition, this article systematically analyses the arguments that have been
      raised. Two elements of the debate are critical: the donor's self-determination
      and consideration for the family and acquaintances. However, the arguments for
      and against the public exhibition of human remains, and the unusual positioning
      of the figurative plastinates seems to be amenable to discussion and also seems
      to allow different ethical weighing. Perhaps this can be understood as an
      indicator that, to start with, discussion is necessary in regard to our general
      burial culture.

PMID- 18342140
TI  - Emil Zuckerkandl (1849-1910): anatomist and pathologist.
AB  - Emil Zuckerkandl (1849-1910), an Austrian anatomist and pathologist, is
      remembered with several eponyms; organ of Zuckerkandl (para-aortic chromaffin
      body), Zuckerkandl's fascia (posterior layer of the renal fascia), Zuckerkandl's
      gyrus (subcallosal area), Zuckerkandl's tuberculum (lateral projection of the
      thyroid gland), Zuckerkandl's operation (perineal prostatectomy), Zuckerkandl's
      dehiscence (fissures in the ethmoid bone), and concha of Zuckerkandl (a rare
      nasal concha). He was a favorite pupil of both Josef Hyrtl (1810-1894) and Carl
      von Langer (1819-1887) at the Vienna School of Anatomy, and succeeded the chair
      of anatomy there. Zuckerkandl strove to make anatomy "subservient" to the patient
      and thus was an early pioneer of clinical anatomy. He was prolific and wrote over
      164 publications at the time of his death. His wife, Berta Zuckerkandl-Szeps, was
      a famous Austrian journalist and a remarkable personality of Jewish society in
      Vienna during the last decades of the Austro-Hungarian Empire until World War II.
      Emil Zuckerkandl left a tremendous legacy regarding anatomical knowledge. This
      early anatomist was credited with the comment that "anatomy is the war map for
      the operations of the physician". This concept gave rise to many surgical
      subspecialities and his anatomical descriptions serve as a basis of our current
      morphological understanding.

PMID- 18342141
TI  - Effect of diagnostic ultrasound during the fetal period on learning and memory in
      mice.
AB  - BACKGROUND: An experiment was conducted to find out whether in utero exposure to
      diagnostic ultrasound leads to changes in postnatal behavior in adult mice.
      METHODS: A total of 15 pregnant Swiss albino mice were exposed to diagnostic
      levels of ultrasound (3.5 MHz, 65 mW/cm(2), intensity((spatial peak-temporal
      peak)) (I(SPTP))=1 mW/cm(2), intensity((spatial average-temporal average))
      (I(SATA))=240 mW/cm(2)) for 30 min on day 14 or 16 of gestation. All exposed as
      well as control animals were left to complete gestation and parturition. Their
      offspring were used in our further studies. They were monitored during early
      postnatal life for standard developmental markers (such as pinna detachment, eye
      opening and fur development) and postnatal mortality was recorded up to 6 weeks
      of age. The litters were subjected to behavioral tests for learning and memory at
      4 months of age. Representative animals from each group were sacrificed and the
      hippocampal region of the brain was assayed for biogenic amines, noradrenaline,
      dopamine, serotonin (5-HT) and 5-HT's metabolite, 5-hydroxy indoleacetic acid (5
      HIAA), in order to determine whether ultrasound exposure produced any biochemical
      changes in the hippocampal region of the brain. Coronal sections from the dorsal
      hippocampus from the representative animals from each group were processed for
      staining and the number of neurons was counted. RESULTS: Neither the standard
      developmental markers (such as pinna detachment, eye opening and fur development)
      nor the postnatal mortality was affected by ultrasound exposure. However, there
      was a significant impairment in learning (hole board test) and memory functions
      (shuttle box test) in both the exposure groups. Significant reductions in the
      biogenic amines and the decrease in the neuronal density were found only in day
      14th pc ultrasound-exposed group compared with the control animals. The 16th day
      exposure group is relatively resistant to ultrasound-induced impairment of brain
      functions. CONCLUSIONS: The results suggest that the early fetal brain is highly
      susceptible to induction of neurobehavioral changes by ultrasound exposure.

PMID- 18342142
TI  - Review of apoptotic and non-apoptotic events in non-ciliated cells of the
      mammalian oviduct.
AB  - Reproductive organs are known to undergo dynamic changes during the oestrus cycle
      and pregnancy. Cell growth and regeneration of the reproductive tissues are
      closely correlated with ovarian steroid hormone levels. This review focuses on
      apoptotic and non-apoptotic degenerative events within oviduct epithelium that
      occur in a species-, cycle-, and segment-specific manner. Epithelial extrusion of
      larger cell fragments including nuclei and whole cells is the characteristic
      feature of non-apoptotic cell loss of non-ciliated cells in large (pig, sheep,
      goat, cattle) and small animals (dog). This mechanism of epithelial cell loss is
      most frequently observed in the luteal phase of the oestrus cycle and after
      progesterone treatment, respectively. Using light- and electron-microscopic
      techniques, typical apoptotic epithelial cells characterized by extensive nuclear
      and cytoplasmic fragmentation are found very sporadically in most species. In
      contrast, oviduct epithelial cells of subhuman primates and cats in part show
      marked signs of apoptosis, which could be explained by their respective cycle
      specific characteristics. Recent investigations using histochemical markers of
      apoptosis and our own findings in the porcine oviduct suggest that the
      degenerative process in the mammalian oviduct includes the death of numerous
      epithelial cells by apoptosis. Advancement in the knowledge of elimination of
      oviduct epithelial cells is necessary to understand the physiological process of
      epithelial renewal and pathological processes caused by imbalances between cell
      renewal and elimination.

PMID- 18342143
TI  - Scanning electron microscopic study of the human auditory ossicles.
AB  - The human mallei, incudes and stapedes from 34 cadavers were examined using
      scanning electron microscope (SEM) to compare the bone surface type among
      different regions of auditory ossicles for males and females. On the malleus of
      both males and females, almost all of the surfaces showed a smooth fibrous
      appearance, characteristic of resting surface. Limited bone-forming or resorbing
      surfaces were identified on the malleus. As compared with the malleus, the
      percentage area of the resorbing surface and the vascular canal openings were
      higher on the incus and stapes, especially on the long process (Crus longum) of
      the incus and the neck of the stapes for both males and females. The percentage
      area occupied by the resorbing surface of the long process of the incus and the
      neck of the stapes correlated with that of the vascular canal openings. We
      consider that the malleus maintained the stable condition, while the long process
      of the incus and the neck of the stapes demonstrated marked bone resorption. We
      suppose that the bone erosion may be related to the vascularization in these
      regions. Though the percentage area of the resorbing surface and the vascular
      canal openings had the tendency to be high in females, we did not find any
      significant differences between the males and females. There was no significant
      correlation between the age and the area of resorbing surface or vascular canal
      openings.

PMID- 18342144
TI  - Regulation of MUC16 by inflammatory mediators in ocular surface epithelial cell
      lines.
AB  - The aim of the present study was to evaluate the regulation of membrane-anchored
      mucin MUC16 by proinflammatory cytokines and bacterial components at the ocular
      surface. Expression and distribution of MUC16 in conjunctival (HCjE) and corneal
      (HCE) epithelial cell lines was monitored by RT-PCR and immunohistochemistry. To
      determine the regulation of MUC16, cultured HCjEs and HCEs were stimulated with
      different cytokines, bacterial components and bacterial supernatants, and
      analyzed by real-time PCR, immunodot blot and immunohistochemistry. The results
      indicate that MUC16 is differentially regulated between HCjEs and HCEs after
      challenge with inflammatory mediators and suggest shedding of MUC16 from the
      ocular surface epithelia into the tear film. This seems to be precisely
      regulated. MUC16 shedding can be differentially increased and decreased,
      suggesting a protective function of membrane-anchored MUC16 and supporting the
      hypothesis that dysregulation of membrane-anchored MUC16 at the ocular surface
      may be involved in dry eye pathology.

PMID- 18342145
TI  - Alteration of gene expression in rat colon mucosa after exercise.
AB  - The development of colon cancer is highly influenced by lifestyle factors such as
      nutrition and physical inactivity. Detailed biological mechanisms are thus far
      unclear. The purpose of this study was to investigate the effects of regular
      treadmill exercise on gene expression in rat colon mucosa. For this purpose, 6
      week-old male Wistar rats completed a stress-free voluntary treadmill exercise
      period of 12 weeks. Sedentary rats served as a control group. In the colon
      mucosa, steady-state mRNA expression levels of approximately 10,000 genes were
      compared between both groups by micro-array analysis (MWG rat 10K array). A total
      of 8846 mRNAs were detected above background level. Regular exercise led to a
      decreased expression of 47 genes at a threshold-factor of 2.0. Three genes were
      found to be up-regulated in the exercise group. The identified genes encode
      proteins involved in signal transduction (n=11), transport (n=8), immune system
      (n=7), cytoskeleton (n=6), protein targeting (n=6), metabolism (n=5),
      transcription (n=3) and vascularization (n=2). Among the genes regulated by
      regular exercise, the betaine-homocysteine methyltransferase 2 (BHMT2) seems to
      be of particular interest. Physical activity may protect against aberrant
      methylation by repressing the BHMT2 gene and thus contribute to a decreased risk
      of developing colon cancer. We have also identified vascular endothelial growth
      factor (VEGF), angiopoietin-2 (ANG-2) and calcium-independent phospholipase a2
      (iPL-A2), all of them with markedly reduced transcript levels in the mucosa of
      active rats. In summary, our experiment presents the first gene expression
      pattern in rat colon mucosa following regular treadmill activity and represents
      an important step in understanding the molecular mechanisms responsible for the
      preventive effect of physical activity on the development of colon cancer.

PMID- 18342146
TI  - The clinical anatomy of the crista terminalis, pectinate muscles and the teniae
      sagittalis.
AB  - The crista terminalis (CT) is an important anatomic landmark due its close
      association with the sinoatrial node artery and the origin of the pectinate
      muscles (PM). However, the gross anatomy of the PM in relation to the CT has not
      been well described. The aim of our study has been to investigate the location
      and the morphology of PM in relation to the CT. We examined 300 adult formalin
      fixed human hearts. All PM originated from the CT and extended along the wall of
      the appendage toward the vestibule of the tricuspid valve. It was observed that
      the PM varied significantly with respect to arrangement and course of its fibers.
      We were able to classify the course of the PM, including the most prominent PM
      called the tenia sagittalis (TS), into 6 different patterns with 3 different TS
      types. In Type A (15%), the TS was absent. Type B (65%) demonstrated a single TS
      and Type C (20%) was characterized by the presence of multiple TS. Furthermore,
      the course of the PM was classified into 6 patterns: Type I (40%), the PM was
      oriented perpendicular to the CT with uniform spacing and lack of crossover
      (trabeculation); Type II (20%), non-uniform PM was organized in a haphazard,
      trabecular fashion with numerous crossovers; Type III (15%), the PM had uniform
      spacing with no trabeculation with fibers oriented parallel to the CT; Type IV
      (10%), had arborizing PM originating from a common muscular trunk (solitary
      trunk); Type V (10%), fibers were oriented both perpendicular and parallel to the
      CT, similar in architecture to Type III, but with more than one common muscular
      trunk; Type VI (5%), prominent muscular column with velamentous PM with potential
      implications in cardiac catheterization procedures. The exact morphology of PM
      and TS may be clinically important in right atrial catheterization procedures, as
      well as in the development of arrhythmias but further investigations are now
      necessary to prove this theory.

PMID- 18342147
TI  - [http://ees.elsevier.com/purol: change, innovation or evolution?].

PMID- 18342148
TI  - [Time-course of plasma testosterone in patients with prostate cancer treated by
      endocrine therapy].
AB  - OBJECTIVE: To assess the time-course of plasma testosterone in patients with
      prostate cancer treated by endocrine therapy. METHODS: A PubMed review of the
      literature on plasma testosterone and the various endocrine therapies for
      prostate cancer was performed. RESULTS: The time-course of plasma testosterone
      varies according to the type of endocrine therapy. The effective castration
      level, classically considered to be 50 ng/dl, is currently tending to be replaced
      by 20 ng/dl. Following surgical castration, plasma testosterone reaches effective
      castration levels within several hours, while with LH-RH agonist therapy, plasma
      testosterone reaches its trough value after three to four weeks, and remains low
      for six months after stopping treatment. However, about 15% of patients treated
      with LH-RH agonists do not achieve effective castration levels. Plasma
      testosterone remains unchanged or even increases in response to anti-androgens.
      Plasma testosterone assay is of limited value in routine clinical practice in
      patients receiving endocrine therapy for prostate cancer, but should be performed
      in the case of elevation of PSA to ensure that the patient has achieved effective
      castration levels. CONCLUSION: The correlation between plasma testosterone and
      progression of prostate cancer is unclear. Other studies are therefore necessary
      to define the value of plasma testosterone assay in patients treated for prostate
      cancer.

PMID- 18342149
TI  - [Prostate cancer and disseminated intravascular coagulation: review of the
      literature].
AB  - Disseminated intravascular coagulation is a rare complication of prostatic cancer
      evolution. Occurring on hormonorefractory phase, it remains most often
      infraclinic. Cases of acute, severe intravascular disseminated coagulation at
      first presentation are life-threatening because of hemorragic and thrombotic
      complications, justifying emergency medical treatment. In the light of a review
      of literature, we insist on epidemiological features, physiopathology and
      therapeutics of intravascular disseminated coagulation. In spite of a pejorative
      prognosis, this could help to achieve a period of remission.

PMID- 18342150
TI  - [Management of male urinary incontinence after radical prostatectomy (CTMH AFU
      2006-1/5): incidence and role of urodynamic assessment and electromyography].
AB  - The incidence of postprostatectomy urinary incontinence varies according to the
      technique used, over time and according to the type of management, with an
      incidence at one year ranging from just a few percent to more than 60%.
      Assessment is required in the case of persistent disabling urinary incontinence
      despite well conducted perineal rehabilitation one year after surgery or earlier
      in the case of severe incontinence. Urodynamic assessment is the essential
      examination to quantify urethral closure pressure. A review of the literature of
      urodynamic assessment and electromyography is presented.

PMID- 18342151
TI  - [Management of male urinary incontinence after radical prostatectomy (CTMH AFU
      2006-2/5): place of perineal rehabilitation and medical treatment].
AB  - The treatment of incontinence is changing, but perineal rehabilitation still
      plays an essential role and is usually able to rapidly and effectively improve
      urinary incontinence. Medical treatment modalities are fairly limited:
      anticholinergic drugs have a limited efficacy except in the case of unstable
      bladder demonstrated by urodynamic assessment and, despite encouraging
      preliminary results, duloxetine has not obtained scientific recognition or
      marketing authorization.

PMID- 18342152
TI  - [Management of male urinary incontinence after radical prostatectomy (CTMH AFU
      2006-3/5): place of periurethral balloon and suburethral tape].
AB  - The treatment of incontinence is changing. Perineal rehabilitation still plays an
      essential role, but new modalities are now available with promising results,
      particularly periurethral balloon and suburethral tape, which may be indicated
      after failure of well-conducted perineal rehabilitation and before artificial
      sphincter. Periurethral balloons consist of two silicone balloons filled with a
      mixture of saline and radiopaque agent inserted transperineally on either side of
      the urethra as close as possible to the bladder neck. Titanium ports connected to
      each balloon allow adjustment of the volume contained in the balloon at any time
      after surgery. This technique appears to be promising but further studies are
      required to clearly define many unresolved issues, including results based on
      longer follow-up and patient selection according to the severity of incontinence
      or their treatment history (radiotherapy). Suburethral tape is used to exert
      permanent static compression of the urethra and was still under development in
      2006. Fairly heterogeneous materials are used and no consensus on this issue has
      yet been reached. Follow-up is still relatively short and few studies have
      addressed the problem of patient selection. Some authors consider that the best
      indication is mild-to-moderate incontinence, which has not yet been clearly
      defined.

PMID- 18342153
TI  - [Management of renal colic in pregnant women, based on a series of 48 cases].
AB  - INTRODUCTION: Urinary stones are relatively frequent in pregnant women and raise
      specific diagnostic and therapeutic problems. The authors conducted a
      retrospective review of the management of this disease in their establishment.
      PATIENTS AND METHODS: Between January 1999 and December 2003, out of a total of
      10,398 parturients, 48 pregnant women were hospitalised for renal colic, that is,
      incidence of 0.04%. The medical records of these patients were retrospectively
      reviewed and clinical, laboratory, treatment and outcome data were analysed.
      RESULTS: Standard analgesic treatment, comprising paracetamol and an
      antispasmodic, achieved pain relief in 84% of cases. A concomitant short course
      of corticosteroid therapy in cases of renal colic refractory to standard
      treatment was effective in 71% of patients and allowed deferral of surgical
      management in five out of seven cases. A double J stent was placed in all
      patients requiring urinary diversion, followed by closer ultrasound and
      bacteriological monitoring throughout pregnancy. Only two patients required
      surgical management of their stone after delivery. The only obstetric event
      related to renal colic was induction of labour at term in two cases because of
      foetal distress. CONCLUSION: The authors propose a two-stage management plan for
      renal colic in pregnant women resulting in a low maternal and foetal complication
      rate.

PMID- 18342154
TI  - [PTa bladder tumours: prognostic factors of recurrence and progression].
AB  - OBJECTIVE: The aim of this work has been to study the prognostic factors of
      recurrence and progression of stage pTa bladder tumours. PATIENTS AND METHODS:
      The case files of 193 patients, consecutively undergoing transurethral resection
      for primary pTa bladder tumour between 1980 and 2003, were retrospectively
      reviewed. Recurrence, progression and specific survival rates were studied.
      Prognostic factors associated with this type of tumour were then investigated.
      RESULTS: After a mean follow-up of 58 months, the recurrence rate was 56.5% and
      the rate of progression to stage T1 was 9.3%. The 10-year specific survival was
      95.8%, but the 10-year recurrence-free survival rate was only 22.5%. Two risk
      factors for recurrence were identified on univariate analysis: haematuria at the
      time of diagnosis (p=0.009) and tumour size (p=0.01). Two factors were associated
      with a risk of progression: tumour size (p=0.03) and relapse during the first
      year after initial resection (p=0.003). None of these factors were independent
      prognostic factors on multivariate analysis. CONCLUSION: pTa bladder tumours
      present a high risk of recurrence. However, with attentive follow-up, the risk of
      progression is low and their 10-year specific survival rate is greater than 95 %.
      Tumour size at the initial diagnosis and early relapse increase the risk of
      progression to more aggressive disease.

PMID- 18342155
TI  - [Correct use of prostate-specific antigen in office practice].
AB  - OBJECTIVE: To standardize interpretation and comments of prostate-specific
      antigen (PSA) assay results by clinical pathology laboratories in office
      practice. MATERIAL: From September 2004 to May 2006, interpretation and comments
      of PSA assay results performed by 100 different laboratories were analysed
      retrospectively. RESULTS: Nineteen different PSA assay kits were used. The so
      called "normal" value for total PSA was less than 4 ng/ml for two-thirds of kits.
      Determination of the free PSA/total PSA ratio (91 cases) was based on a cut-off
      value ranging from 10 to 25% and the frequent laboratory comments (89 cases) more
      often referred to benign prostatic hyperplasia (51 case) than prostate cancer
      (nine cases). CONCLUSION: The marked diversity of PSA assay techniques currently
      used and the divergent interpretations by various laboratories lead to problems
      of interpretation for both practitioners and patients.

PMID- 18342156
TI  - [General practical survey of individual prostate cancer screening].
AB  - OBJECTIVE: To assess the practices of general practitioners in the Auvergne
      region concerning individual prostate cancer screening, to compare these
      practices with published guidelines and to identify those points that are most
      difficult to perform. MATERIAL: An anonymous postal survey using a predefined
      questionnaire was conducted among 1339 general practitioners in the Auvergne
      region identified by the URSSAF file on 1st January 2006. This was a declarative
      survey with no individual financial reward. The questionnaire comprised three
      aspects: general practitioner identification criteria, screening practices and
      the doctors' opinion concerning guidelines. RESULTS: The participation rate was
      49.1: 98.3% of general practitioners declared that they proposed screening and
      89.5% declared that they proposed screening to all men within certain age limits,
      from 50 to 75 years in 80.8% of cases. Only 4.6% of doctors provided complete
      preliminary information to their patients. Among the doctors,75.6% combined
      digital rectal examination and total PSA assay, but in the presence of an
      abnormality, only 10.5% referred their patients directly to an urologist without
      prescribing other complementary investigations (first- or second-line). Finally,
      53.5% of doctors considered that published guidelines were adapted to their
      clinical practice. CONCLUSION: Individual prostate cancer screening is massively
      proposed, but differences are observed between the doctors' reported practices
      and official guidelines. This study emphasizes the need to provide patients with
      clear and complete information and to improve the general practitioners'
      knowledge on screening tests and patient referral in the case of positive
      screening tests.

PMID- 18342157
TI  - [Observational survey on variations of prostate cancer incidence by stage in the
      Nord-Pas-de-Calais region between 1998 and 2004].
AB  - OBJECTIVE: The aim of this work is to study variations of prostate cancer
      incidence by stage as a function of time and place in a region of France.
      MATERIAL AND METHODS: Retrospective observational survey conducted in five
      private and public urology centres representative of the various demographic
      features of the Nord-Pas-de-Calais region. In each centre, the medical records of
      the first 25 cases of prostate cancer diagnosed in 1998, 2002 and 2004,
      identified from histology laboratory data, were studied by means of a case report
      form evaluating the circumstances of diagnosis, PSA level, grade, stage (TNM 97,
      classification) and initial management. RESULTS: This analysis was based on 123,
      124 and 125 patients in five centres in 1998, 2002 and 2004, respectively. The
      age at diagnosis ranged from 71.14 to 68.9 years between 1998 and 2004 (p=0.054).
      Median PSA decreased over this six-year period from 18 to 10.8 ng/ml. Between
      1998 and 2004, the percentage of patients with localized cancer (PSA<20 ng/ml)
      increased from 44.8 to 66.4% (p<0.05), the percentage of patients with locally
      advanced cancer (PSA between 20 and 50 ng/ml) decreased from 17 to 9.6% (p<0.05),
      the percentage of patients with regional or distant metastatic disease (N1 and/or
      M1 and/or PSA>50 ng/ml) decreased from 29.4 to 22.4% (p<0.05) and the percentage
      of patients receiving curative treatment increased from 30 to 54.4% (p<0.005).
      CONCLUSION: The prostate cancer incidence by stage varied between 1998 and 2004,
      with a significantly higher proportion of localized stages, which can be
      explained by the increased use of screening and diagnostic tests. Routine surveys
      can measure trends and the amplitude of incidence variations in the population of
      a region. A representative survey conducted in centres throughout France would
      allow evaluation of national trends between two publications of incidence by
      stage results in French registries.

PMID- 18342158
TI  - [Retropubic, laparoscopic and robot-assisted total prostatectomies: comparison of
      postoperative course and histological and functional results based on a series of
      86 prostatectomies].
AB  - OBJECTIVE: Compare three surgical approach procedures of total prostatectomy
      (retropubic, transperitoneal laparoscopic and robot-assisted laparoscopic), about
      technical, oncological and functional results. METHODS: Eighty-six patients had a
      total prostatectomy for localized cancer, in a unique center, performed by two
      expert surgeons, on a 16-months-period. Twenty nine had a retropubic, 23 a
      transperitoneal laparoscopic and 34 a robot-assisted (Da Vinci) surgical
      approach. Retrospectively, operative time, blood loss, per- and postoperative
      complications, duration of catheterization, length of hospital stay, in each
      group had been compared. The positive margin rates, the PSA levels at one and six
      months postoperative had been compared. The continence has also been evaluated at
      six months. RESULTS: The three groups are comparable even if the median age is
      significatively lower in the retropubic group (p=0.018). Duration of catheter
      (p<2.2 x 10(-16)), blood loss (p<3.12 x 10(-5)) and operative times support
      significatively the laparscopic approaches, clearer the conventional than the
      robot-assisted one. No significative difference has been shown about positive
      margin rates, even if it's higher in the robot-assisted group (p=0.37). Finally,
      the continence rate is quite higher in the laparoscopic groups without statistic
      significativity (76 % retropubic versus 96.8 % laparoscopic and 85.3 % robot
      assisted). CONCLUSIONS: The conventional laparoscopic and robot-assisted
      approaches seem to present technical advantages. Nevertheless, pathologic results
      are shader: the positive margin rate in the robot-assisted group is higher, in
      particular regarding to pT2. These results are concordant with the available
      datas of the literature.

PMID- 18342159
TI  - [Treatment by iterative endoscopic retroperitoneal adrenalectomy of an ectopic
      adrenal adenoma revealed by a Cushing syndrome].
AB  - We report a case of a Cushing syndrome, enduring after retroperitoneal
      laparoscopic bilateral adrenalectomy whose aetiology was an ectopic adenoma. This
      lesion had then been treated by a secondary retroperitoneal laparoscopic
      procedure.

PMID- 18342160
TI  - [Abdominoscrotal hydrocele complicated by hydroureteronephrosis].
AB  - Abdominoscrotal hydrocele is a very rare clinical entity especially in childhood
      with less than 100 paediatric cases reported in the literature. It is associated
      with various complications and its pathogenesis is still a matter for debate. The
      authors report a case of abdominoscrotal hydrocele in the child. The methods of
      the diagnosis as well as the specific treatment are pointed out.

PMID- 18342161
TI  - Update on smoking cessation interventions for the primary care physician.
      Introduction.

PMID- 18342162
TI  - Nonpharmacologic therapy for smoking cessation: characteristics and efficacy of
      current approaches.
AB  - This article reviews the most common nonpharmacologic approaches used to support
      smoking cessation and, where possible, provides estimates of their efficacy in
      controlled clinical trials. Virtually all of the approaches that have been
      systematically evaluated to date have demonstrated modest efficacy in increasing
      quit rates. A cornerstone of effective treatment is tobacco dependence
      counseling, for which there is a dose-response relation between the intensity of
      counseling (total minutes of contact) and its effectiveness. New approaches in
      which treatment is tailored to individual patient characteristics appear
      promising for the future but require further study. Also, new technologies that
      permit delivery of smoking interventions to a wider range of patients could have
      a significant impact on reducing smoking prevalence worldwide in the future.
      Overall, the clinical literature strongly endorses combining nonpharmacologic
      interventions with pharmacotherapy to optimize support for smokers who are trying
      to quit.

PMID- 18342163
TI  - Update on pharmacologic options for smoking cessation treatment.
AB  - Although the proportion of the adult population in the United States that smokes
      has decreased steadily, the rate of successful quit attempts is still low.
      Smokers develop nicotine dependence that resembles other addictions, and may
      require multiple attempts and long-term treatment to sustain abstinence.
      Currently available first-line agents for smoking cessation therapy include
      nicotine replacement therapy, which is available in several formulations,
      including transdermal patch, gum, nasal spray, inhaler, and lozenge; bupropion,
      an atypical antidepressant; and varenicline, a partial agonist of the
      alpha(4)beta(2) nicotinic acetylcholine receptor that was recently developed and
      approved specifically for smoking cessation therapy. Second-line agents are
      nortriptyline, a tricyclic antidepressant agent, and clonidine, an
      antihypertensive drug. With the exception of varenicline, which has been shown to
      offer significant improvement in abstinence rates over bupropion, all of the
      available treatments appear similarly effective. However, the adverse event
      profiles of nortriptyline and clonidine make them more appropriate for second
      line therapy, when first-line treatments have failed or are not tolerated.
      Rimonabant, a cannabinoid-1 receptor antagonist that was being developed for
      smoking cessation, received a nonapprovable letter from the FDA in 2006 and there
      is no further information as to whether development for this indication is
      continuing for this agent. Nicotine vaccines are under investigation and offer
      promise, especially for relapse prevention. Ultimately, selection of
      pharmacologic agent should be based on the patient's comorbidities and
      preferences, as well as on the agent's adverse event profile.

PMID- 18342164
TI  - Neurobiology of nicotine addiction: implications for smoking cessation treatment.
AB  - Nicotine sustains addictive tobacco use, which in turn causes much premature
      disability and death. The essence of drug addiction is loss of control of drug
      use. Molecular biology studies suggest that the alpha(4)beta(2) nicotinic
      acetylcholine receptor subtype is the main receptor mediating nicotine
      dependence. Nicotine acts on these brain nicotinic cholinergic receptors to
      facilitate neurotransmitter release (dopamine and others), producing pleasure,
      stimulation, and mood modulation. Neuroadaptation develops with repeated exposure
      to nicotine, resulting in tolerance to many of the effects of nicotine. When a
      smoker stops smoking, a nicotine withdrawal syndrome ensues, characterized by
      irritability, anxiety, increased eating, dysphoria, and hedonic dysregulation,
      among other symptoms. Smoking is also reinforced by conditioning, such that
      specific stimuli that are psychologically associated with smoking become cues for
      an urge to smoke. These include the taste and smell of tobacco, as well as
      particular moods, situations, and environmental cues. Pharmacotherapies to aid
      smoking cessation should ideally reduce nicotine withdrawal symptoms and block
      the reinforcing effects of nicotine obtained from smoking without causing
      excessive adverse effects. Further, given the important role of sensory effects
      of smoking and psychoactive effects of nicotine, counseling and behavioral
      therapies are important adjuncts to and substantially augment the benefits of
      pharmacotherapy.

PMID- 18342165
TI  - Efficacy and safety of varenicline for smoking cessation.
AB  - Effective treatment of nicotine addiction is essential for reducing the
      substantial current and predicted morbidity and mortality associated with tobacco
      smoking. Despite the availability of effective treatments for smoking cessation,
      such as nicotine replacement therapy and bupropion sustained-release (SR),
      abstinence rates remain less than optimal. Varenicline is the first in a new
      class of agents for smoking cessation, the alpha(4)beta(2) nicotinic
      acetylcholine receptor (nAChR) partial agonists. Nicotine addiction is mediated
      by stimulation of central alpha(4)beta(2) nAChRs by nicotine, which causes the
      release of dopamine, ultimately leading to the pleasurable effects of smoking. As
      a nAChR partial agonist, varenicline attenuates the craving and withdrawal
      symptoms that occur with abstinence from nicotine and also reduces the rewarding
      effects of nicotine obtained from smoking in patients who lapse. Thus,
      varenicline offers a new therapeutic option for the treatment of nicotine
      addiction. Clinical trials have demonstrated superior efficacy of this agent over
      placebo and bupropion-SR for achieving abstinence from smoking, and varenicline
      has also been shown to significantly delay smoking relapse. As the newest agent
      approved for smoking cessation, the mechanism of action, efficacy, and safety of
      varenicline.

PMID- 18342166
TI  - Port site metastasis and tumor seeding in oncologic laparoscopic urology.
AB  - Tumor seeding and port site metastasis remain a valid concern during laparoscopic
      procedures for urologic malignancies. A systematic review of all cases reported
      in published studies was performed. A MEDLINE search identified 17 English
      studies reporting a total of 29 cases of port site metastasis or tumor seeding
      secondary to urologic laparoscopic procedures in the past 20 years. Many factors
      contribute to port site metastases and tumor seeding. Nevertheless, we believe
      that only proper preoperative criteria, along with cautious intraoperative
      judgment, will keep port site metastasis to a minimum in the future.

PMID- 18342167
TI  - Citrate levels in fresh tomato juice: a possible dietary alternative to
      traditional citrate supplementation in stone-forming patients.
AB  - OBJECTIVES: To detect citrate levels in fresh tomato juice, to reveal whether it
      can be studied for prevention of recurrent hypocitraturic nephrolithiasis.
      METHODS: Juices of tomato, orange, lemon, and mandarin were extracted and blended
      with a hand blender, and 10 samples of 100 mL were taken from each. Citrate,
      oxalate, calcium, phosphorus, magnesium, sodium, potassium, chloride, and pH
      levels were examined in these. The same variables were re-evaluated after the
      samples were stored at +4 degrees C for 1 week. RESULTS: In fresh tomato juice,
      higher citrate and magnesium levels as well as lower sodium and oxalate levels
      were detected as compared with the other juices. No differences were observed
      with regard to all variables among fresh orange, lemon, and mandarin juices. The
      level of citrate in the fresh tomato juice was higher at a statistically
      significant level than that in tomato juice that was stored for 1 week. The
      amount of oxalate increased in stored tomato juice. CONCLUSIONS: Fresh tomato
      juice is considered a rich source of citrate. Furthermore, a high level of
      magnesium and a low level of sodium and oxalate content were detected in fresh
      tomato juice, the usability of which in recurrent hypocitraturic nephrolithiasis
      can be investigated in clinical studies.

PMID- 18342169
TI  - Prospective comparison of magnetic resonance angiography with selective renal
      angiography for living kidney donor assessment.
AB  - OBJECTIVES: For years, the reference standard in the evaluation of living donor
      vascular anatomy has been selective renal angiography (SRA). Because of the
      potential morbidity associated with SRA, we prospectively evaluated magnetic
      resonance angiography (MRA) in the assessment of renal donors. METHODS: All
      patients had SRA and 53 renal units were prospectively evaluated by MRA. We used
      SRA supplemented by findings at donor nephrectomy (DN) as our standard. We
      defined a positive test as the detection of any abnormality in the number of
      renal arteries. RESULTS: Selective renal angiography yielded a sensitivity of
      86%, specificity of 95%, positive predictive value (PPV) of 75%, and negative
      predictive value (NPV) of 97% compared with findings at DN. MRA had a sensitivity
      of 64%, 88% specificity, 58% PPV, and 90% NPV. MRA correctly identified only 7 of
      11 renal units with accessory arteries. MRA also incorrectly identified 5
      accessory arteries not present on SRA or DN. Two patients diagnosed with
      fibromuscular dysplasia by SRA were missed using MRA. CONCLUSIONS: We have shown
      that MRA is not capable of replacing SRA as the reference standard in renal donor
      imaging.

PMID- 18342170
TI  - Optimal measure of PSA kinetics to identify prostate cancer.
AB  - OBJECTIVES: To compare different tools for evaluate prostate-specific antigen
      (PSA) kinetics before prostate biopsy, such as PSA velocity, PSA slope, natural
      logarithm PSA slope (lnPSA slope), and PSA doubling time (PSADT). METHODS: This
      study was conducted involving 325 male patients evaluated with transrectal
      ultrasound-guided biopsy of prostate. Patients with at least three consecutive
      PSA measurements taken in at least 24 months entered in the study. We estimated
      PSA slope from the slope of the least squares regression line fit to PSA versus
      time in years; PSA velocity was calculated as the running average of the rate of
      change during at least three consecutive assays. The acceleration of PSA (lnPSA
      slope) was calculated as the slope of lnPSA versus time, where ln is the natural
      logarithm. PSADT was calculated using the formula: PSADT = ln 2/(lnPSA slope).
      RESULTS: We found a total of 74 cancers at the ultrasound guided prostate
      biopsies. At the receiver operating characteristic (ROC) analysis, lnPSA slope
      (area under the curve [AUC], 0.793) evidenced better results than PSA (AUC,
      0.585; P <0.001), PSA velocity (AUC, 0.734; P <0.009), PSA slope (AUC, 0.752; P
      <0.043), and PSADT (AUC, 0.516; P <0.001). CONCLUSIONS: The results for PSA, PSA
      velocity, PSA slope, and lnPSA slope were significantly higher in patients with
      prostate cancer than in controls. The results of the present study suggest that
      lnPSA slope may be useful for prostate cancer diagnosis. At the ROC analyses, the
      lnPSA slope AUC was better than that of PSA, PSA velocity, PSA slope, and PSADT.

PMID- 18342171
TI  - Relationship of prostate-specific antigen and prostate volume in Korean men with
      biopsy-proven benign prostatic hyperplasia.
AB  - OBJECTIVES: To investigate the relationship between prostate-specific antigen
      (PSA) and prostate volume in a histologically defined subset of Korean men
      confirmed to have benign prostatic hyperplasia (BPH) only from multicore biopsy
      of prostate. METHODS: A total of 707 Korean men with a PSA level of 10 ng/mL or
      lower who were shown to have stromoglandular hyperplasia only from transrectal
      ultrasound (TRUS)-guided multicore biopsy of prostate were included in the study.
      We analyzed PSA and total prostate volume (TV) measured through TRUS by
      stratified age cohorts. We used Pearson correlation coefficient (r) and linear
      regression model to describe the relationship between variables. RESULTS: Serum
      PSA level significantly correlated with TV in all stratified age cohorts, with r
      ranging from 0.29 to 0.47 (all P <0.001). Meanwhile, the degree of correlation
      appeared to increase with age. The slope of linear regression showing an
      association of PSA and TV was 3.68. The PSA increase per unit prostate volume
      decreased with the advancing cohort of age when we excluded subjects 70 years or
      older. CONCLUSIONS: Although PSA was significantly correlated with TV, the exact
      nature of the relationship between PSA and TV in Korean men with biopsy-proven
      BPH may be different from that in other races. Further basic research on the
      pathophysiology of BPH is needed to explain such a racial difference.

PMID- 18342172
TI  - Saturation prostate biopsy in high risk patients after multiple previous negative
      biopsies.
AB  - OBJECTIVES: To evaluate the diagnostic value of saturation prostate biopsy in
      patients with prostate-specific antigen (PSA) greater than 10 ng/mL, PSA velocity
      greater than 0.75 ng/mL/year, free PSA ratio less than 0.2, and at least 3 sets
      of negative biopsy specimens. METHODS: Twenty-seven patients underwent the
      procedure with the use of a transrectal approach under general or regional
      anesthesia. A systematic coverage of the peripheral zone was accomplished by
      maintaining a fixed distance between punctures (5 mm). In addition, multiple
      cores were obtained from the transition zone bilaterally, bladder neck, and
      midline according to a strict preplanned template. RESULTS: The mean number of
      cores obtained per patient was 61.7 +/- 9.5 (range 41 to 76). Average PSA was
      19.4 +/- 8.5 ng/mL (range 10.1 to 49). Prostate cancer (Gleason score 3+3) was
      found in 3 patients (11.1%). All 3 patients who received a diagnosis of cancer
      had minimal disease affecting less than 1% of a single core sampled from the
      peripheral zone. Two patients were designated for watchful waiting and 1 patient
      chose radical prostatectomy. His pathologic specimen contained carcinoma of
      prostate (Gleason 3+3) in less than 1% of the total prostate volume. All patients
      were discharged within 24 hours after the procedure. Asymptomatic bacteremia was
      documented in 1 patient. Two patients had epididymitis develop and were treated
      conservatively. CONCLUSIONS: According to our findings, saturation prostate
      biopsy has low diagnostic yield in patients who previously had at least 3 sets of
      negative traditional biopsy specimens. In all the cases, that prostate cancer was
      found, it had histologic features consistent with biologically insignificant
      disease.

PMID- 18342173
TI  - Surgeons' perceptions and injuries during and after urologic laparoscopic
      surgery.
AB  - OBJECTIVES: The biomechanical and mental strains placed on the surgeon while
      performing laparoscopic procedures are significantly higher compared with open
      surgical techniques. We undertook this study to assess the prevalence of
      surgeons' deleterious perceptions or injuries related to laparoscopic urologic
      surgery. METHODS: Members of endourological society were mailed a questionnaire
      evaluating their laparoscopic experience, total number of standard laparoscopic
      surgeries (SLS), hand-assisted laparoscopic surgeries (HALS), and robotic
      assisted laparoscopic surgeries (RALS) they performed. The subjects reported any
      neuromuscular or arthritic injuries sustained during laparoscopic surgery, and
      graded the degree of pain, numbness, and fatigue they experienced. RESULTS: A
      total of 73 urologists completed the questionnaires. The average responder was 44
      years old, had completed a median of 117 procedures, and was performing 3
      laparoscopic surgeries per week. Neuromuscular or arthritic symptoms during
      surgery were reported by 22 responders (30%), the most common was finger
      paresthesia (18%). At the conclusion of HALS, 45% of the surgeons suffered from
      hand and wrist numbness and 37% reported pain in these areas. A significant
      association was observed between the risk of sustaining injury during surgery and
      the total number of laparoscopic procedures performed by the responder (P =
      0.016). RALS was the procedure least associated with injuries, and HALS the most.
      CONCLUSIONS: The laparoscopic operating theater is a hostile ergonomic
      environment. Surgeons' awareness of the common injuries associated with
      laparoscopic surgery and careful equipment adjustments before surgery are
      mandatory to minimize injury. Future improvements in instrument design according
      to ergonomic principles are highly warranted.

PMID- 18342174
TI  - Functional and morphological effects of postpercutaneous nephrolithotomy
      superselective renal angiographic embolization.
AB  - OBJECTIVES: To evaluate the functional and morphological effects of
      postpercutaneous nephrolithotomy (PCNL) superselective renal angiographic
      embolization. METHODS: Between January 1995 and March 2006, superselective renal
      angiography was needed to control severe bleeding after 41 of 4095 PCNL
      procedures (1%). We evaluated the short-term effects of embolization after 3
      months with renal ultrasonography (RUS), dimercaptosuccinic acid (DMSA) renal
      scan, and estimation of serum creatinine. We evaluated long-term morphological
      and functional effects with RUS, DMSA renal scan, and excretory urography (IVU).
      RESULTS: Bleeding was controllable with superselective embolization in 38
      patients (93%). Six of them developed early postembolization complications, in
      the form of perinephric hematoma in 4 and urinary leakage in 2 patients. At 3
      months, serum creatinine levels increased in 3 of 9 patients with a solitary
      kidney, but none required renal replacement therapy. Long-term follow-up was
      completed for 30 patients for a mean period of 3.9 +/- 2.3 years. We performed
      IVU for 27 patients. Among them, 2 renal units (7%) showed no dye excretion. DMSA
      scans showed homogeneous distribution of radiotracer with no evidence of
      photopenic areas in 6 renal units (20%). The mean percentage of DMSA uptake by
      the corresponding kidney improved from 25 +/- 9% at the 3-month scans to 34 +/-
      11% at the last follow-up scans (P <0.001). CONCLUSIONS: The short-term
      deleterious effects of superselective renal embolization for post-PCNL renal
      vascular injuries were more pronounced in patients with a solitary kidney.
      However, the long-term follow-up showed functional and morphological
      improvements.

PMID- 18342175
TI  - Comparing lymphadenectomy during radical nephroureterectomy: open versus
      laparoscopic.
AB  - OBJECTIVES: Laparoscopic nephroureterectomy (LNU) is an accepted treatment for
      tumors of the ureter and renal pelvis, although the ability to perform a regional
      lymphadenectomy has been criticized. We compared the quality of lymphadenectomy
      with LNU with that involving open nephroureterectomy (ONU) to determine whether
      oncologic principles are maintained. METHODS: We searched our institutional
      database for patients who had undergone ONU from 1990 to 2005. These were
      compared with a series of patients from January 2003 to April 2007 who underwent
      LNU. From each patient's medical records, we assessed the number of lymph nodes
      removed, the number of positive nodes removed, and the density of positive nodes.
      The differences between groups were analyzed using the Wilcoxon rank sum
      statistical test. RESULTS: We identified 106 patients who underwent ONU with
      lymphadenectomy and 28 who underwent LNU with lymphadenectomy. The median number
      of nodes removed, median number of positive nodes, and median density of positive
      nodes were, respectively, 3, 0, and 0 for the ONU group; and 6, 0, and 0, for the
      LNU group. There was a statistically significant difference between groups with
      respect to the number of nodes removed (P = 0.01) but not with respect to the
      number of positive nodes removed (P = 0.61) or the lymph node density (P = 0.42).
      CONCLUSIONS: Offsetting the benefits of laparoscopy could be a flawed oncologic
      technique. We have demonstrated that lymphadenectomy, which is a potentially
      important component of nephroureterectomy, can be performed as well during LNU as
      it is with ONU when a dedicated effort is made.

PMID- 18342176
TI  - Issue of prostate gland size, laparoscopic radical prostatectomy, and continence
      revisited.
AB  - OBJECTIVES: To evaluate the influence of prostate gland size on the
      perioperative, pathologic, and continence outcomes after laparoscopic radical
      prostatectomy (LRP). METHODS: 144 LRPs for which 18-month continence data were
      available were performed by a single surgeon, and were retrospectively reviewed.
      Patients were divided initially into two groups based on final prostate gland
      size: group 1 (weight less than 50 g) and group 2 (weight 50 g or more). Group 2
      patients were stratified into group IIa (weight 50 to 70 g) and Group IIb (weight
      70 g or more) to further examine the effect of gland size on continence. RESULTS:
      Larger glands had higher mean prostate-specific antigen (P <0.05) but among
      groups there were no significant differences in patient age, Gleason sum,
      pathological stage, operative time, intraoperative blood loss, or positive margin
      rate. We noted a significant difference in mean time to recovery of continence
      for patients with small glands versus large glands: group 1 (8.2 months), group 2
      (9.9 months), group IIa (8.5 months), and group IIb (13.8 months) (P <0.05).
      CONCLUSIONS: Prostate gland size had no effect on perioperative outcomes.
      However, recovery of postoperative continence can be delayed in patients with
      large prostates.

PMID- 18342177
TI  - Transperitoneal laparoscopic radical nephrectomy for large (more than 7 cm) renal
      masses.
AB  - OBJECTIVES: To evaluate our laparoscopic radical nephrectomy (LRN) series to
      determine whether any significant increases have occurred in operative morbidity
      when resecting large (7 cm or greater) renal masses. LRN is becoming the
      reference standard for treating suspicious renal masses not amenable to nephron
      sparing surgery. METHODS: We retrospectively reviewed the charts of 164
      consecutive patients who had undergone laparoscopic radical nephrectomy performed
      for suspicious renal masses by two surgeons from February 2000 and December 2006.
      After institutional review board approval, we reviewed the patient charts to
      determine whether patients with 7-cm or larger lesions had significant
      differences in age, body mass index, American Society of Anesthesiologists class,
      operative time, estimated blood loss, conversion rate, positive margin rate,
      postoperative creatinine, and hematocrit compared with patients with lesions
      smaller than 7 cm. RESULTS: The data from 164 patients were reviewed. Of these
      164 patients, 124 had less than 7-cm masses and 40 had lesions 7 cm or larger.
      The mean tumor size in the less than 7-cm group was 4.2 cm (range 1.8 to 6.9) and
      was 9.2 cm (range 7 to 14) in the 7-cm or larger group. The patients with large
      tumors had a significantly longer operative time, greater estimated blood loss,
      and increase in postoperative serum creatinine than those with smaller tumors but
      all other perioperative variables were similar. Two conversions to open radical
      nephrectomy occurred in both groups. CONCLUSIONS: Our data have clearly shown
      that larger tumors can safely be resected with transperitoneal laparoscopic
      nephrectomy. Open nephrectomy for large tumors can be associated with increased
      morbidity and the use of LRN could minimize this increased risk. Urologists with
      laparoscopic experience should consider expanding their indication for LRN.

PMID- 18342179
TI  - Urethroplasty, by perineal approach, for bulbar and membranous urethral
      strictures in children and adolescents.
AB  - OBJECTIVES: To evaluate the safety and efficacy of urethroplasty for bulbar and
      membranous urethral strictures using the perineal approach in children and
      adolescents. Urethroplasty by the perineal approach is considered the best
      treatment for bulbar and membranous urethral strictures in adults. It is not as
      clear whether this also holds true in children, because the published data
      addressing this question are scant. METHODS: We retrospectively reviewed our
      urethroplasty database to identify patients who had undergone urethroplasty using
      the perineal approach surgery at age 1 to 13 years (children) and 14 to 18 years
      (adolescents). RESULTS: A total of 14 patients who had undergone urethroplasty by
      the perineal approach were identified, including 5 children (mean age 10.8 years)
      and 9 adolescents (mean age 16.7 years). Of the 14 patients, 7 had membranous and
      7 bulbar urethral strictures. The membranous strictures were all secondary to
      pelvic fractures. The bulbar strictures were "idiopathic" in 57%, traumatic in
      29%, and secondary to hypospadias in 14%. All bulbar strictures had been
      previously treated for 2.5 years, on average, by repeated dilation or urethrotomy
      that failed. Anastomotic urethroplasty was used in 79% of the patients and tissue
      transfer techniques in the remainder. The mean follow-up was 30 months (range 12
      to 54). Surgery was primarily successful in 93% of the patients, and subsequently
      successful in 100%. The mean maximal urinary flow increased from 2.65 mL/s
      preoperatively to 27.65 mL/s postoperatively. No significant complications
      occurred, and success was similar in both groups. CONCLUSIONS: In pediatric
      patients, as in adults, bulbar and membranous strictures can be treated
      successfully with urethroplasty using the perineal approach. These patients
      should probably not be treated "conservatively" with urethral dilation or
      endoscopic incision. Longer follow-up is needed to confirm that these good
      results are maintained as these patients cross into adulthood, especially for
      those who underwent repair before puberty.

PMID- 18342178
TI  - Prostate mechanical imaging: a new method for prostate assessment.
AB  - OBJECTIVES: To evaluate the ability of prostate mechanical imaging (PMI)
      technology to provide an objective and reproducible image and to assess the
      prostate nodularity. METHODS: We evaluated the PMI device developed by Artann
      Laboratories in a pilot clinical study. For the 168 patients (ages 44 to 94) who
      presented to an urologist for prostate evaluation, PMI-produced images and
      assessment of prostate size, shape, consistency/hardness, mobility, and
      nodularity were compared with digital rectal examination (DRE) findings. The PMI
      and DRE results were further tested for correlation against a transrectal
      ultrasound of the prostate (TRUS) guided biopsy for a subgroup of 21 patients
      with an elevated prostate-specific antigen level. RESULTS: In 84% of the cases,
      the PMI device was able to reconstruct three-dimensional (3D) and 2D cross
      sectional images of the prostate. The PMI System and DRE pretests were able to
      determine malignant nodules in 10 and 6 patients, respectively, of the 13
      patients with biopsy-confirmed malignant inclusions. The PMI System findings were
      consistent with all 8 biopsy negative cases, whereas the DRE had 1 abnormal
      reading for this group. The correlation between PMI and DRE detection of palpable
      nodularity was 81%, as indicated by the area under the receiver operating
      characteristic curve. Estimates of the prostate size provided by PMI and DRE were
      statistically significantly correlated. CONCLUSIONS: The PMI has the potential to
      enable a physician to obtain, examine, and store a 3D image of the prostate based
      on mechanical and geometrical characteristics of the gland and its internal
      structures.

PMID- 18342182
TI  - Utility of dextranomer/hyaluronic acid injection in setting of bladder and
      ureteral anomalies.
AB  - OBJECTIVES: Previous studies have shown that the cure rates after
      dextranomer/hyaluronic acid (Dx/HA) injection can be decreased in patients with
      neurogenic bladder, previous ureteroneocystostomy, duplicated ureters, or
      periureteral diverticula. We attempted to determine whether these factors reduce
      the efficacy of Dx/HA injection compared with that in otherwise normal patients.
      METHODS: All children with vesicoureteral reflux (VUR) undergoing Dx/HA injection
      from April 2002 to March 2006 at two institutions were eligible for this study.
      Multivariate logistic regression models were built to assess the effect of
      bladder/ureteral anomalies on the success of Dx/HA injection. We adjusted for
      previously described predictors of injection success, including VUR grade, sex,
      age, surgeon experience, and injection technique. RESULTS: A total of 543
      refluxing ureters (373 patients) were included, of which 145 (27%) had persistent
      VUR on postoperative voiding cystourethrography; 86 ureters (16%) had anatomic
      anomalies. On univariate analysis, the most important predictors of injection
      failure were increasing VUR grade, male sex, younger age, subureteral injection,
      ureteral duplication anomaly, increasing Dx/HA volume, and surgeon experience. On
      multivariate analysis, however, the only significant predictors of injection
      failure were increasing VUR grade, subureteral injection technique, and surgeon
      experience. No anatomic or functional abnormalities, considered individually or
      grouped, significantly affected the probability of injection failure.
      CONCLUSIONS: In our experience, children with functional and anatomic
      bladder/ureteral anomalies were no more likely to have Dx/HA injection fail than
      were children with uncomplicated VUR. The most important predictors of Dx/HA
      success remained VUR grade, injection technique, and surgeon experience. Dx/HA
      injection in patients with complex bladders could be a reasonable therapeutic
      option.

PMID- 18342183
TI  - Renal ultrasonography should be done routinely in children with first urinary
      tract infections.
AB  - OBJECTIVES: To assess the consequences of renal ultrasonography (RUS) in the
      treatment of children younger than 5 years of age with a first febrile urinary
      tract infection. METHODS: We retrospectively reviewed the results of imaging
      studies, including RUS, computed tomography, and voiding cystourethrography in
      children with a first febrile urinary tract infection during a 2-year period.
      Children with known urologic anomalies, other underlying diseases, or
      simultaneous combined illnesses were excluded. Children with nephromegaly were
      diagnosed with acute lobar nephronia by computed tomography. RESULTS: A total of
      390 children were included in this study. Of the 390 children, 112 (28.7%) had
      abnormal RUS findings. The children with abnormal RUS findings of nephromegaly,
      small kidney, intermittent hydronephrosis, or a double collecting system had a
      significantly greater incidence of vesicoureteral reflux than children with
      normal RUS findings. Additionally, the occurrence of high-grade vesicoureteral
      reflux in children with abnormal RUS findings was more frequent than in children
      with normal RUS findings. CONCLUSIONS: The results of our study indicate that it
      is worth performing RUS in children with a first febrile urinary tract infection
      because abnormal kidney size or other specific structural ultrasound findings
      should be investigated, in addition to isolated hydronephrosis.

PMID- 18342184
TI  - Evidence-based criteria for pain of interstitial cystitis/painful bladder
      syndrome in women.
AB  - OBJECTIVES: No diagnostic physical signs, urologic findings, or laboratory tests
      are available for interstitial cystitis/painful bladder syndrome (IC/PBS). Its
      diagnosis is determined by symptoms and the exclusion of mimicking diseases. We
      hypothesized that certain pain characteristics are sensitive criteria for
      diagnosing IC/PBS. METHODS: In women with recent-onset IC/PBS recruited in 2004
      to 2006 for the case-control study, "Events Preceding Interstitial Cystitis," we
      identified the locations of each patient's pain and in a nonleading way asked
      about the effects of 17 different experiences (criteria) on the pain. We
      identified a set of criteria that described the largest number of patients in the
      Events Preceding Interstitial Cystitis study. In a secondary analysis of another
      cohort recruited by others in 1993 to 1997, the Interstitial Cystitis Database,
      we determined the proportion of patients captured by these same criteria.
      RESULTS: In the Events Preceding Interstitial Cystitis study, pain that worsened
      with a certain food or drink and/or worsened with bladder filling and/or improved
      with urination was reported by 151 (97%) of 156 patients. These were the only
      three criteria that applied directly to the bladder. The same three criteria
      described the pain of 262 (97%) of 270 women in the Interstitial Cystitis
      Database who "definitely" had IC/PBS. CONCLUSIONS: An hypothesis generated in one
      IC/PBS patient group and tested in another--pain that worsened with certain food
      or drink and/or worsened with bladder filling and/or improved with urination--was
      described by 97% of the patients with IC/PBS in each cohort. This triad might
      describe the pain of IC/PBS and contribute to a sensitive case definition.
      Estimating specificity awaits comparison with other diseases with similar
      symptoms.

PMID- 18342185
TI  - Trospium 60 mg once daily (QD) for overactive bladder syndrome: results from a
      placebo-controlled interventional study.
AB  - OBJECTIVES: A once-daily (QD) formulation of trospium chloride has been developed
      for the management of overactive bladder syndrome (OAB). This randomized
      controlled trial evaluated the efficacy and tolerability of this new extended
      release formulation, trospium chloride 60 mg QD. METHODS: Adults with OAB with
      urinary urgency, frequency, and urgency urinary incontinence (UUI) were eligible
      for inclusion. Subjects received trospium 60 mg QD or placebo for 12 weeks.
      Change in the mean number of toilet voids per day and UUI episodes per day were
      the primary outcome variables. Changes in urgency severity were also assessed and
      adverse events (AEs) were recorded. RESULTS: Overall, 564 subjects participated
      in the study (trospium QD 280; placebo 284). Trospium QD demonstrated significant
      improvement in both primary outcome variables. The mean number of toilet voids
      per day was reduced from approximately 13 at baseline to 10.3 for trospium QD
      versus 11.1 for placebo (P <0.001) at week 12, whereas the number of UUI episodes
      per day was reduced from approximately 4 at baseline to 1.7 at week 12 with
      trospium QD versus 2.4 for placebo (P <0.001). Trospium QD also reduced urgency
      severity (P <0.001) and increased voided volume (P <0.01) compared with placebo.
      Benefits over placebo were apparent within the first week of treatment. Trospium
      QD was well tolerated; the most frequent AEs being dry mouth (trospium QD 12.9%;
      placebo 4.6%) and constipation (7.5% versus 1.8%, respectively). Central nervous
      system side effects were rarely observed and were comparable between groups.
      CONCLUSIONS: Trospium QD represents a convenient, effective, and well-tolerated
      treatment option for OAB.

PMID- 18342186
TI  - Urodynamic assessment of poor responders after botulinum toxin-A treatment for
      overactive bladder.
AB  - OBJECTIVES: Botulinum toxin-A (BTX-A) is effective in treating overactive bladder
      (OAB) refractory to anticholinergics. Most patients have improvements in
      symptoms, urodynamic parameters, and quality of life, and a poor response is
      uncommon. The aim of this study was to determine whether poor responders could be
      predicted from preoperative urodynamic parameters. METHODS: Data were collected
      prospectively from 33 OAB patients with idiopathic detrusor overactivity. All
      patients underwent intradetrusor injections of 200 U BTX-A. Response to treatment
      was assessed by patient perception, OAB symptoms, and quality of life data.
      Urodynamics were conducted at baseline and 4, 12, and 24 weeks postinjection. We
      performed statistical analysis using the Wilcoxon matched pairs, Mann-Whitney,
      two-sample, and paired t-tests. Receiver operator characteristic (ROC) curves
      were plotted for relevant parameters. RESULTS: Five patients had a poor response
      to treatment. Significant increases in maximum cystometric capacity (MCC), reflex
      detrusor volume (RDV), and bladder compliance with decreases in maximum detrusor
      pressures (MDP) on filling were observed in the responders over 24 weeks. Minimal
      urodynamic benefit was observed in the poor responders group over the same
      period. When comparing the two groups, baseline MDP in poor responders was 138.0
      +/- 30.7 compared with 74.4 +/- 32.6 in the responders (P = 0.0028). ROC analysis
      suggested that a pretreatment MDP greater than 110 may have predictive value
      (AUC, 0.946; sensitivity, 0.86; specificity, 1.0) for a poor response to
      treatment. CONCLUSIONS: Very high MDP greater than 110 may predict a poor
      response to treatment with 200 U of BTX-A. Higher doses may be necessary in these
      patients.

PMID- 18342187
TI  - Role of trospium chloride in brachytherapy-related detrusor overactivity.
AB  - OBJECTIVES: After prostate brachytherapy, pronounced urinary irritative
      symptomatology occurs in a substantial minority of patients. In this study, we
      evaluated the impact of trospium chloride in prostate brachytherapy patients with
      symptoms consistent with an overactive bladder (OAB). METHODS: From January 1999
      through December 2005, 69 permanent prostate brachytherapy patients were
      identified who received trospium as first-line treatment for OAB. The median
      interval from implant to initiation of trospium was 23.4 months. Before trospium,
      we obtained a postvoid residual urine assessment (PVR) and International Prostate
      Symptom Score (IPSS) for all patients. IPSS resolution was defined as a return to
      within 2 points of the pre-brachytherapy value and individual IPSS question
      resolution was defined by a decrease of at least 1 point. RESULTS: The mean
      patient age was 66.0 years, with a pre-brachytherapy prostate volume of 31.0
      cm(3) and a mean preimplant IPSS of 6.5. At trospium initiation, the mean IPSS
      was 9.6 with a mean PVR of 12.3 mL. IPSS normalization was documented in 55
      (79.7%) patients. Twelve months after trospium initiation, the IPSS had decreased
      by a mean of 4.3 points with the improvement most pronounced for urgency. After
      trospium, no clinically significant differences were noted in the mean PVR.
      Twenty-two patients discontinued trospium as a result of the absence of a
      clinical response or pharmacologic side effects, or after complete resolution of
      symptoms. CONCLUSIONS: Nearly 80% of patients with brachytherapy-related detrusor
      overactivity responded favorably to trospium with improvements in IPSS
      (especially urgency). This was accomplished with an acceptable morbidity profile.

PMID- 18342188
TI  - Uroflowmetric differences between standing and sitting positions for men used to
      void in the sitting position.
AB  - OBJECTIVES: To compare the results of uroflowmetry in the standing and sitting
      position in men who void only in the sitting position. METHODS: Two hundred
      patients were subjected to pelvic ultrasonography while their bladders were full,
      and then after voiding. Uroflowmetry was done both in sitting and standing
      positions and compared for all patients. Further comparisons were made according
      to patients' age (below and above 50) and Qmax (at or below 15 mL per second
      versus greater than 15 mL per second). We performed statistical analysis using
      Wilcoxon matched-pairs signed-ranks test. RESULTS: Comparison of uroflowmetric
      results in both positions showed no statistical differences except for
      significantly larger residual urine volume in the standing position (86.1 +/- 77)
      relative to the sitting position (73 +/- 80.2) (P = 0.04). On substratifying
      patients according to age, Qmax was significantly higher in the sitting position
      (16.6 +/- 8.94) relative to the standing position (15.2 +/- 7.5) in the young
      group (P = 0.02). Such a significant difference was not seen in the elder
      (greater than 50 years) group. In contrary to the low-flow group, cases with high
      flow showed significantly higher Qmax and Qave and significantly lower voiding
      and flow times and significantly lower residual urine volume in the sitting
      position. CONCLUSIONS: Voiding in the sitting position showed significantly
      better flow rates than during standing in patients with higher flow and younger
      age. Moreover, postvoid residual was significantly less in the sitting position
      in the previous two groups and in the total groups of patients. On the contrary,
      the presence of low flow nullifies these uroflowmetric positional differences.
      Uroflowmetry should be always performed in the preferred position.

PMID- 18342189
TI  - Diagnostic and predictive value of voiding diary data versus prostate volume,
      maximal free urinary flow rate, and Abrams-Griffiths number in men with lower
      urinary tract symptoms suggestive of benign prostatic hyperplasia.
AB  - OBJECTIVES: To investigate the information of voiding data in relation to
      symptoms and well-being in men with lower urinary tract symptoms (LUTS)
      suggestive of benign prostatic hyperplasia (BPH) and to compare this information
      with that of prostate volume (Vprostate), maximal free urinary flow rate
      (Q(max,free)), and obstruction grade (OG). METHODS: We performed mandatory tests,
      recommended tests, and pressure-flow studies in 384 consecutive men with LUTS
      suggestive of BPH. We estimated nocturia, diuria, and mean voided volume (Vmean)
      from their voiding diaries. Symptoms and well-being were quantified by American
      Urological Association symptom index (SI), quality-of-life score (QoL), symptom
      problem index (SPI), and BPH impact index (BII). We investigated the influence of
      Vprostate, Q(max,free), OG, Vmean, nocturia, and diuria on SI, QoL, SPI, and BII.
      We re-evaluated 48 men 6 months after transurethral resection of the prostate
      (TURP). We analyzed the predictive value of preoperative Q(max,free), Vprostate,
      OG, Vmean, nocturia, and diuria for the improvements of SI, QoL, SPI, and BII
      after TURP. We studied the improvements of Q(max,free), OG, Vmean, nocturia, and
      diuria after TURP and the improvements of SI, QoL, SPI, and BII. RESULTS:
      Prostate volume, Q(max,free), and OG were only slightly associated with SI, QoL,
      SPI, and BII, in contrast to Vmean, nocturia, and diuria. The predictive value of
      all parameters on the outcome of TURP was poor. Improvements of all parameters
      were strongly associated with improvements of SI, QoL, SPI, and BII after TURP.
      CONCLUSIONS: Voiding data should have a prominent role in the initial evaluation
      of men with LUTS suggestive of BPH.

PMID- 18342190
TI  - Longitudinal association between prostatitis and development of benign prostatic
      hyperplasia.
AB  - OBJECTIVES: To determine whether physician-diagnosed prostatitis was associated
      with later development of benign prostatic hyperplasia (BPH)-associated events in
      a longitudinal, population-based sample of 2447 men residing in Olmsted County,
      Minnesota. METHODS: Medical records were reviewed for physician diagnosis of
      prostatitis and subsequent diagnoses of BPH, enlarged prostate, prostatism, and
      acute urinary retention. Records were also reviewed for medical or surgical
      treatments for BPH. Odds ratios were calculated to assess the associations
      between physician-diagnosed prostatitis and later development of development of
      BPH-associated events. RESULTS: Physician-diagnosed prostatitis was associated
      with a 2.4-fold increased odds of receiving a later diagnosis of prostatism,
      enlarged prostate, or BPH (OR: 2.44, 95% CI: 1.48, 4.01). Prostatitis was also
      associated with a 70% increased odds of requiring later treatment for BPH (OR:
      1.69, 95% CI: 1.28, 2.22), and a non-significant increased odds of acute urinary
      retention (OR: 1.33, 95% CI: 0.89, 1.99). CONCLUSIONS: Physician-diagnosed
      prostatitis was associated with an increased risk of later onset of several BPH
      associated events. Physician-diagnosed prostatitis may therefore be an early
      marker or a risk factor for development of later prostatic or urologic problems.

PMID- 18342192
TI  - Impotence and suing for sex in eighteenth-century England.
AB  - OBJECTIVES: To explore the individual and social experiences and meanings of
      impotence in 18th-century England. METHODS: Close reading and period
      contextualization of various primary source records about impotence, including
      legal documents from lawsuits for nullity of marriage by reason of impotence,
      bestselling medical texts, and cheap pornographic pamphlets was done. RESULTS:
      Contemporary, humoral and mechanical medicine and physiology characterized
      impotence by various etiologies and patient presentations. This left room for
      laymen, and especially women, to diagnose and interpret the condition according
      to their own devices. A matter of public, as well as private, concern, impotence
      carried with it the meanings of failed masculinity, neglected civic
      responsibility, foreignness, and Catholicism. CONCLUSIONS: Impotence in 18th
      century England served as a catch-all diagnosis for sexual dysfunction and a
      vehicle through which to address anxieties about the stability of patriarchal
      power, female deceit, religion, and politics. Today, medicine, physiology, and
      the disease itself are very different, but the individual and social meanings of
      impotence remain influential and worthy of consideration.

PMID- 18342193
TI  - Effects of varicocele repair in adults on ultrasonographically determined
      testicular volume and on semen profile.
AB  - OBJECTIVES: We determined the effect of varicocele repair on testicular volume
      according to scrotal ultrasonography, reported to provide the best approximation
      of actual testicular volume. METHODS: Forty-four men with left varicocele (mean
      age +/- standard deviation, 33.4 +/- 5.4 years) underwent varicocele repair. We
      performed both scrotal ultrasonography with color Doppler imaging and semen
      analysis before and after varicocele repair. Among these patients, 19 had a
      clinical left varicocele, 22 had clinical left and subclinical right varicoceles,
      and 3 had clinical left and right varicoceles. We calculated testicular volumes
      using the formula: Length x Width x Height x 0.71. RESULTS: For all 44 patients,
      mean left and total testicular volume improved significantly after varicocele
      repair (increases of 1.5 and 2.4 mL, respectively) as did semen profile data such
      as sperm per unit volume and percentage of motile sperm. In the 19 men with a
      clinical left varicocele, mean left testicular volume increased significantly (by
      1.5 mL) after left varicocele repair, in association with increases in sperm per
      unit volume and motility percentage. In the 25 men with clinical left varicocele
      plus a subclinical or clinical right varicocele, mean left and total testicular
      volume improved significantly after repair of right and left varicoceles
      (increases of 1.5 and 2.7 mL, respectively). However, right testicular volume
      showed no significant increase in any patient group. CONCLUSIONS: Varicocele
      repair in adults with a clinical left varicocele increased left testicular volume
      and improved semen profiles.

PMID- 18342194
TI  - Age-related increase of reactive oxygen species in neat semen in healthy fertile
      men.
AB  - OBJECTIVES: The effects of advancing paternal age on the male reproductive system
      are well known, but its effects on fecundity remain controversial. Although
      oxidative stress is associated with poor semen quality and function, a
      relationship with advancing male age has not been established. The objective of
      this study was to analyze the relationship between male age and seminal reactive
      oxygen species (ROS) levels in men presenting for voluntary sterilization.
      METHODS: We prospectively evaluated 98 fertile men who were candidates for
      vasectomy. These were divided into 2 age groups: less than 40 years (n = 78) and
      40 or more years (n = 20). We used 46 infertile patients as positive controls.
      Standard semen analysis, seminal leukocyte count and ROS levels were measured in
      all samples. Fertile men with leukocytospermia were excluded. RESULTS: The mean
      age of the men was 35.1 +/- 5.6 years. Men 40 years and older had significantly
      higher ROS levels compared with younger men (P <0.001). We observed a positive
      correlation between seminal ROS levels and age (r = 0.20; P = 0.040). In
      addition, ROS was negatively correlated with sperm concentration (r = -0.48; P
      <0.001) and motility (r = -0.21; P = 0.030). CONCLUSIONS: Reactive oxygen species
      levels are significant higher in seminal ejaculates of healthy fertile men older
      than 40 years. ROS levels in whole ejaculate are significantly correlated to age
      among fertile men. Because ROS are clearly implicated in the pathogenesis of male
      infertility, these data suggest that delayed fatherhood may reduce the chances of
      pregnancy as men become progressively less fertile with age.

PMID- 18342195
TI  - Single center preliminary experience with hand-assisted laparoscopic resection of
      isolated renal cell carcinoma fossa recurrences.
AB  - OBJECTIVES: Solitary metastasis to the renal fossa after radical nephrectomy for
      renal cell carcinoma is uncommon. We report the first series on hand-assisted
      laparoscopic excision for renal cell carcinoma fossa recurrences. METHODS: We
      performed a retrospective review of patients who underwent hand-assisted
      laparoscopic excision of renal cell carcinoma fossa recurrence. Patients with
      distant metastasis or local lymph node or adrenal metastasis were excluded from
      analysis. We collected data on patient and tumor characteristics, nephrectomy and
      fossa mass excision procedures, and postoperative outcomes. RESULTS: Between 2001
      and 2007, 5 patients underwent laparoscopic resection of a renal fossa
      recurrence. Mean time to recurrence after radical nephrectomy was 23 months
      (range, 5 to 46 months) and mean size of the renal fossa mass was 6 cm (range,
      4.2 to 9.5 cm). The average operative time was 232 minutes (range, 150 to 300
      minutes) and average estimated blood loss was 175 mL (range, 25 to 400 mL). One
      patient required conversion to open surgery. There were no postoperative
      complications and mean hospital stay was 4 days. With mean follow-up of 43
      months, the cancer-specific and disease-free survival rates were 60% and 20%,
      respectively. Of the 4 patients who underwent complete resection, 2 died from
      metastatic disease at 13 and 56 months, 1 continues to have progressive
      metastatic disease at 69 months, and 1 remains free of any clinical evidence of
      metastatic disease or recurrence at 37 months. One patient who underwent
      incomplete resection as a result of inferior vena cava invasion continues to have
      progressive local and distant metastatic disease at 40-month follow-up.
      CONCLUSIONS: Hand-assisted laparoscopic excision of renal fossa recurrence after
      radical nephrectomy appears to be safe and effective for carefully selected
      patients.

PMID- 18342197
TI  - Prostate-specific antigen doubling time is a reliable predictor of imageable
      metastases in men with biochemical recurrence after radical retropubic
      prostatectomy.
AB  - OBJECTIVES: To examine the incidence of imageable metastases at the time of
      biochemical recurrence after radical prostatectomy and to determine whether
      prostate-specific antigen doubling time (PSADT) reliably predicts these imageable
      metastases. METHODS: Between October 2000 and October 2005, 1112 men underwent
      open radical retropubic prostatectomy by a single surgeon. All men were advised
      to undergo bone scintigraphy and an abdominal/pelvic imaging study at the time of
      biochemical recurrence. We ascertained the sensitivity, specificity, and positive
      and negative predictive values of a PSADT cut-point of 3 months to predict the
      presence of imageable metastases. RESULTS: Seventy-four (6.7%) men developed a
      biochemical recurrence and imageable metastases were demonstrable in 7 cases.
      Imageable metastases were identified in 11.3% and 7.5% of men undergoing bone
      scans and abdominal/pelvic imaging, respectively. Extracapsular extension, and
      older age positive surgical margins, and PSADT were associated with a
      significantly greater risk of exhibiting imageable metastases. The sensitivity,
      specificity, and positive and negative predictive values of a PSADT cut-point of
      3 months for predicting imageable metastasis were 100%, 98.0%, 87.5%, and 100%,
      respectively. CONCLUSIONS: A relatively small proportion of men at the time of
      developing biochemical recurrence after radical prostatectomy exhibit imageable
      metastasis. The 100% sensitivity and negative predictive value of a PSADT cut
      point of 3 months strongly suggests that PSADT can be used as an excellent proxy
      for imageable metastasis. Omitting routine bone scintigraphy and body imaging at
      the time of biochemical recurrence minimizes the costs, inconvenience, and
      anxiety associated with these studies.

PMID- 18342198
TI  - Asians with localized prostate cancer treated with 3-dimensional conformal
      radiation therapy and adjuvant hormonal therapy: comparing Phoenix and American
      Society of Therapeutic Radiology and Oncology (ASTRO) definitions in an Asian
      population.
AB  - OBJECTIVES: Conformal radiotherapy with adjuvant androgen suppression is used in
      our center to treat localized prostate cancer. We compare Phoenix as an
      alternative to American Society of Therapeutic Radiology and Oncology (ASTRO) for
      defining biochemical failure. Our primary aim was to assess the Phoenix and ASTRO
      definitions of biochemical failure in a population of mainly Asian men with early
      localized prostate cancer treated with conformal radiotherapy with and without
      androgen ablation. METHODS: We retrospectively analyzed 141 patients who were
      treated for T1/T2 cancer of the prostate in our center from January 1997 to June
      2002 with a mean duration of follow-up of 62 months. Outcomes were analyzed by
      using both Phoenix and ASTRO definitions of biochemical failure as well as
      clinical failure. RESULTS: The Phoenix definition of biochemical failure was
      superior as measured by sensitivity, specificity, positive and negative
      predictive values, accuracy, and a greater concordance with clinical outcome as
      measured by Kappa analysis. CONCLUSIONS: The ASTRO definition helped to
      standardize reporting of biochemical failures post-radiotherapy but inadequacies
      have been identified especially when adjuvant hormone therapy has been given. The
      Phoenix definition has been noted to be a more accurate and precise description
      of biochemical failure in international series, and we find this to be true in
      our Asian population as well.

PMID- 18342199
TI  - Screening and management of prostate cancer in elderly men: the Iowa Prostate
      Cancer Consensus.
AB  - OBJECTIVES: The issue of prostate cancer screening and management is likely to
      assume greater importance with progressive aging of the population. Because there
      are no currently established guidelines for screening and management of prostate
      cancer in elderly men (older than 75 years), a multidisciplinary panel was
      convened to develop consensus recommendations. METHODS: The panel consisted of
      experts in urology, internal medicine/geriatrics, medical oncology, radiation
      oncology, family practice, law, patient advocacy and physician assistants. Four
      internationally known experts on prostate cancer served as external advisors.
      Relevant literature was reviewed and consensus was developed based on expert
      opinion, given the lack of level I evidence regarding most aspects of prostate
      cancer diagnosis and management in men older than 75 years of age. RESULTS: On
      the basis of the opinions of the expert panel, recommendations for screening and
      management of prostate cancer in elderly men older than 75 years of age was
      developed. In general, there was support for using greater discretion in
      screening for prostate cancer in elderly men. The lack of adequate patient
      education tools to facilitate discussion with patients was recognized. There was
      also agreement on the need for greater and renewed patient counseling regarding
      benefits and risks of prostate cancer screening beyond age 75. CONCLUSIONS: It is
      possible to build consensus around a standardized approach to prostate cancer
      screening and management in older men. Promulgation of such consensus
      recommendations and their widespread adoption may help engender a tailored
      approach to managing prostate cancer in older men, thereby decreasing health care
      costs and morbidity while limiting unnecessary therapy.

PMID- 18342200
TI  - Ten-year biochemical disease control for patients with prostate cancer treated
      with cryosurgery as primary therapy.
AB  - OBJECTIVES: Prostate cryosurgery has been increasingly used for the management of
      localized prostate cancer since its introduction in a minimally invasive form in
      the early 1990s. We performed a retrospective study of the largest and most
      mature patient group treated with cryosurgery reported thus far. METHODS: We
      retrospectively analyzed the data from 370 patients treated consecutively from
      1991 to 1996 with a focus on the determination of biochemical disease-free
      survival for a group of patients with T1 to T3 prostate cancer who had undergone
      prostate cryosurgery as primary monotherapy. Only patients with no previous
      radiotherapy, hormonal therapy, or surgery were included. RESULTS: The median
      follow-up was 12.55 years. Using a nadir plus 2 ng/dL definition, Kaplan-Meier
      analysis demonstrated a biochemical disease-free survival rate at 10 years of
      80.56%, 74.16%, and 45.54% for low, moderate, and high-risk groups, respectively.
      The 10-year negative biopsy rate was 76.96%. CONCLUSIONS: The results for this
      pilot group of patients who underwent percutaneous prostate cryosurgery
      monotherapy demonstrated biochemical disease-free survival rates that overlap
      with those of similar groups of patients treated under similar circumstances
      using other types of nonextirpative monotherapy.

PMID- 18342201
TI  - Clinical model of cost of bladder cancer in the elderly.
AB  - OBJECTIVES: To develop a population-based clinical model of bladder cancer (BC)
      care costs and identify cost drivers. METHODS: We retrospectively reviewed a
      cohort of 4863 patients with BC identified from the linked Surveillance,
      Epidemiology and End Results-Medicare database, aged at least 65 years and
      diagnosed between 1994 and 1996. We collected the records of Medicare
      reimbursements (a surrogate of costs) through 1998 and classified them into
      clinically relevant intervals and care types by disease invasiveness to derive
      the cumulative costs of care. We calculated the incremental resource use costs
      using sex and age-matched controls from a 5% general population sample and
      compared similarly matched patients with other cancer (OC). We inflated all costs
      to 2006 U.S. dollars. RESULTS: The annual cost of care for all patients with
      muscle-invasive BC (MIBC) was $35.72M (95% confidence interval $35.69M to
      $35.75M), 70% more than the $21.03M (95% confidence interval $21.00M to $21.05M)
      for patients with non-MIBC. The major cost drivers, regardless of disease stage,
      were diagnostic/surveillance and complications, accounting for up to 43% and 37%
      of BC care costs, respectively. Comorbidity-adjusted incremental annual resource
      costs per patient with MIBC were more than four times greater than those for
      patients with non-MIBC, similar to those of OC controls (P = 0.490-0.913), except
      for inpatient (P = 0.002) and hospice (P <0.001) costs, which were both
      statistically significantly lower. Annual adjusted incremental Medicare
      reimbursements totaled $36.3M for non-MIBC and $96.1 million for MIBC.
      CONCLUSIONS: The results of this study have indicated that a reduction of BC care
      costs could be realized with strategies inhibiting disease progression and
      reducing the occurrence and severity of complications.

PMID- 18342202
TI  - Effects of phosphodiesterase inhibitors on tension induced by norepinephrine and
      accumulation of cyclic nucleotides in isolated human prostatic tissue.
AB  - OBJECTIVES: To further evaluate the mechanism of action of phosphodiesterase
      (PDE) inhibitors on the human prostate, the effects of PDE4 and PDE5 inhibitors
      on the tension induced by norepinephrine (NE) and on the intracellular levels of
      cyclic nucleotides in isolated human prostatic tissue were investigated. METHODS:
      Using the organ bath technique, the effects of increasing concentrations (1 nM to
      10 microM) of the PDE5 inhibitors sildenafil, tadalafil, and vardenafil and the
      PDE4 inhibitors rolipram and RP 73401 on the tension induced by NE (40 microM) of
      prostate strip preparations were investigated. The accumulation of cyclic
      guanosine monophosphate and cyclic adenosine monophosphate in response to drug
      exposure was determined by radioimmunoassays. RESULTS: The tension induced by NE
      was dose dependently reversed by the drugs with the following rank order of
      efficacy: tadalafil greater than RP 73401 greater than rolipram greater than or
      equal to vardenafil greater than sildenafil. The maximal reversion of tension
      values ranged from 52.3% (tadalafil) to 17% (sildenafil). Of the PDE inhibitors,
      only tadalafil induced a 50% reversion of the initial tension. The most prominent
      enhancement in tissue cyclic adenosine monophosphate was registered in response
      to RP 73401 (11-fold), and cyclic guanosine monophosphate levels were
      significantly elevated by tadalafil, vardenafil, and sildenafil (28-fold, 12
      fold, and 3-fold, respectively). CONCLUSIONS: Our results have demonstrated that
      drugs interfering with the cyclic nucleotide-mediated pathways can reverse the
      tension induced by NE in isolated prostatic tissue and elevate cyclic adenosine
      monophosphate and cyclic guanosine monophosphate. Our findings serve to explain
      how PDE inhibitors can affect symptoms of lower urinary tract symptoms and benign
      prostatic hyperplasia.

PMID- 18342203
TI  - Solar ultraviolet B radiation compared with prostate cancer incidence and
      mortality rates in United States.
AB  - OBJECTIVE: To investigate whether the prostate cancer incidence and mortality
      rates in the United States correlate inversely with solar ultraviolet (UV) B
      radiation levels computed from a mathematical model using forecasted ozone
      levels, cloud levels, and elevation. Another objective was to explore whether the
      annual prostate cancer rates correlated more strongly with the cumulative UVB
      exposure for the year or for exposure during certain seasons. METHODS: The age
      adjusted incidence and mortality cancer rates for black and white men in the
      continental United States were correlated with the mean UV index values averaged
      for the year and for each season. RESULTS: We found an inverse correlation
      between the UVB levels and prostate cancer incidence (R = -0.42, P <0.01) and
      mortality rates (R = -0.53, P <0.001) for white men and for incidence (R = -0.40,
      P <0.05) for black men, but the strength of the correlation depended on the
      season of UVB irradiance. No statistically significant results for black male
      mortality were found. The annual prostate cancer incidence and mortality rates
      for white men correlated most strongly with UVB exposure levels in the fall and
      winter, and incidence rates for black men correlated with UVB exposure levels in
      the summer. CONCLUSIONS: Increased solar UVB radiation might reduce the risk of
      prostate cancer, but the efficacy depends on the season of UVB irradiance.

PMID- 18342204
TI  - Proteomic investigation on chronic bladder irritation in the rat.
AB  - OBJECTIVES: Interstitial cystitis (IC) is a painful bladder syndrome associated
      with urinary frequency and urgency. Elusive cause of IC makes its diagnosis only
      possible by exclusion in many cases. In this study, we used proteomics for
      identifying disease-associated proteins in a rat model of chronic bladder
      irritation. METHODS: Chronic irritation of the rat bladder was caused by a brief
      (90 seconds) intravesical instillation of 0.2 mL of 0.4 N HCl. Whole bladders
      were collected at different time points after treatment, snap frozen, and nuclear
      and cytosolic protein extracts were obtained. Samples were resolved in standard 2
      dimensional (2D) gels stained with an improved Coomasie stain or by differential
      gel electrophoresis (DIGE). Differentially expressed spots were excised and
      identified by MALDI-TOF MS/MS. Histologic and Western blot analyses were also
      performed. RESULTS: Bladder morphology and histologic appearance of bladder
      sections after HCl treatment reflected hemorrhage, edema, epithelial denudation,
      detrusor mastocytosis, and eosinophilia. Proteomic analysis of irritated rat
      bladder revealed marked overexpression of 4 nuclear proteins and marked
      underexpression of 1 nuclear protein compared with normal rat bladders. Among
      these proteins, inflammation-associated calgranulin A (over) and smooth muscle
      protein-22/transgelin (under) showed opposed expression patterns after bladder
      irritation. CONCLUSIONS: Presence of mast cells and eosinophils and
      overexpression of calgranulin A confirm the inflammatory component of HCl
      irritated bladder. Altered expression of nuclear proteins is of particular
      interest because of their possible role as a prognostic marker in inflammatory
      bladder disorders. However, more studies are needed before clinical application
      of these findings can be established.

PMID- 18342205
TI  - Effect of age on the role of Rho-kinase in short-term partial bladder outlet
      obstruction.
AB  - OBJECTIVES: We examined the expression of Rho-kinase (ROK) isoforms in young and
      old rabbits' detrusor smooth muscles (SM) during the progression of short-term
      partial bladder outlet obstruction and correlated them with the time course of
      obstruction. METHODS: We obtained detrusor samples from bladders after 1, 3, 7,
      and 14 days of obstruction and also sham-operated control rabbits. We used
      reverse transcriptase-polymerase chain reaction, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis, and Western blotting to determine the
      relative levels of ROK isoform expression at the mRNA and protein levels.
      RESULTS: Bladder weight for young rabbits increased between 1 and 7 days'
      obstruction and came back toward control levels at 14 days' obstruction. In old
      rabbits, bladder weight increased after obstruction, reaching a maximum at 3 days
      and remaining at this level throughout the 14 days. In young rabbits, the
      expression of ROKalpha increased in 1- to 7-day obstructed groups and decreased
      in the 14-day group, whereas it increased progressively in the old rabbits at
      both the mRNA and protein levels. There was a significant decrease in the
      expression of ROKbeta in young obstructed rabbits, which gradually decreased
      during the course of 1- to 7-day obstruction period and increased after 14 days
      of obstruction. In old groups, there was a decrease in expression after 1 day of
      obstruction and values remained at a decreased level throughout the course of the
      study. CONCLUSIONS: Young rabbit bladders are better able to adapt to bladder
      outlet obstruction and ROK isoforms respond in a similar way.

PMID- 18342206
TI  - Granular cell tumor of the glans penis in a 9-year-old boy.
AB  - Granular cell tumor of the penis is a rare lesion, especially in the pediatric
      population. We present a case of a 9-year-old white boy with a granular cell
      tumor of the glans penis, as well as a review of literature. We also discuss
      clinical management and subsequent implications pertinent to lesion location.

PMID- 18342207
TI  - First male apocrine genital carcinoma mimicking a penile cancer.
AB  - Perineal apocrine carcinoma is a rare malignant tumor that has its origin in the
      apocrine sudoriparous glands of the genital and perianal regions. It often
      progresses quietly and metastasizes in the superficial inguinal and retrorectal
      lymph nodes. We report a case of a genital apocrine carcinoma located at the
      penile basis. To our knowledge our report represents the first case of a
      pathologically confirmed genital apocrine carcinoma mimicking a penile cancer.

PMID- 18342208
TI  - Osteuria.

PMID- 18342209
TI  - Long-term remission of metastatic small cell carcinoma of the prostate.
AB  - Metastatic small cell carcinoma of the prostate portends a poor prognosis.
      Survival expectancy is generally estimated in months with few reports in the
      literature of patients surviving more than 2 years. We report a case of one of
      the longest known surviving patients in continuous complete remission with
      metastatic small cell carcinoma of the prostate and review the available
      literature reporting longer-term survival in this condition.

PMID- 18342210
TI  - A case of portal venous gas after extracorporeal shockwave lithotripsy and
      obstructive pyelonephritis.
AB  - The presence of gas in the portal venous system is considered an ominous sign
      often mandating immediate exploratory laparotomy; however, there are numerous
      reports of benign incidences of this finding. This report describes a case of
      portal venous gas after extracorporeal shockwave lithotripsy. The patient had the
      rare complication of obstructive pyleonephritis that progressed to sepsis and
      subsequently underwent a negative exploratory laparotomy. It is suggested that
      the radiographic finding of portal venous gas should be correlated with the
      likely cause and overall clinical picture.

PMID- 18342211
TI  - Plexiforme neurofibroma with compromising of the penile function.
AB  - The objective of this article was to describe a case of Von Recklinghausen's
      disease with plexiform neurofibroma of the penis. The patient was 26 years old
      and reported difficulty with sexual intercourse owing to a penile mass, despite
      experiencing normal sensation and erection. Physical examination demonstrated
      this penile mass with cafe au lait spots, subcutaneous neurofibromas, and lisch
      nodules. The treatment consisted of subcoronal incision and resection of the
      lesion. Pathologic examination revealed a plexiform neurofibroma. The patient
      recovered well with subsequent maintenance of penile sensation and erection. In
      cases of plexiform neurofibroma compromising penile function, total resection of
      penile mass offers a good therapeutic option.

PMID- 18342212
TI  - Wegener's granulomatosis presenting as a renal mass.
AB  - Wegener's granulomatosis is a systemic necrotizing vasculitis that usually
      involves the kidneys, typically causing segmental necrotizing glomerulonephritis.
      An association between Wegener's granulomatosis and renal cell carcinoma was
      recently reported. We describe a case of Wegener's granulomatosis presenting as a
      renal mass in a 72-year-old woman. Histologic examination of the mass revealed
      granulomatous inflammation, an extremely rare manifestation of this disease. We
      also review the incidence of renal mass in Wegener's granulomatosis and highlight
      the importance of excluding the coexistence of renal cell carcinoma.

PMID- 18342213
TI  - Laparoscopic findings of transverse testicular ectopia.
AB  - Transverse testicular ectopia (TTE) is an extremely rare congenital anomaly in
      which both testes descend through the same inguinal canal. We report an 8-month
      old male with TTE and hypospadias. To help manage the patient, we conducted
      laparoscopy to elucidate the anatomy of the spermatic cord of the ectopic testis.
      On laparoscopy, we clearly identified the spermatic cord of the right ectopic
      testis. In addition, the laparoscopic guide was helpful when doing the trans
      septal orchidopexy, in that the ectopic testis could be precisely discriminated
      without confusion as to the laterality of the testes. Long-term follow-up at 32
      months confirmed that both testes were properly positioned in the scrotum and had
      a good consistency.

PMID- 18342214
TI  - Extra-nodal small cell lymphocytic lymphoma of prostate: an unusual cause of
      lower urinary tract symptoms.
AB  - Malignant lymphoma of the prostate is a rare occurrence. We describe a case of 60
      year-old man presenting with acute urinary retention due to small cell
      lymphocytic secondary lymphoma of the prostate. We present the clinical
      manifestation of the disease emphasizing that all lower urinary tract symptom
      (LUTS) cases should be evaluated for the potential that metastatic cancers or
      lymphomas may present with such a diagnosis. We also present and tabulate a
      detailed review of at least 5 such similar reports (in which LUTS was the
      presenting symptom) published in the English literature to date.

PMID- 18342215
TI  - [Criteria of choice of an antibiotic in 2007: Efficiency for the patient-
      Conservation of the bacterial ecology].

PMID- 18342217
TI  - [Pristinamycin use in the treatment of acute exacerbations of COPD (COPD =
      chronic obstructive pulmonary disease)].

PMID- 18342219
TI  - [Pristinamycin use in the treatment of acute maxillary sinusitis in adults].

PMID- 18342220
TI  - [In Process Citation].

PMID- 18342221
TI  - Cardiogenic and aortogenic brain embolism.
AB  - Cardioaortic brain embolism is a potentially devastating condition that presents
      frequent diagnostic and therapeutic challenges. In this report, we review key
      aspects of the etiology, clinical presentation, diagnosis, prognosis, and
      treatment of cardiogenic and aortogenic stroke. Emphasis is on advances in
      diagnostic imaging capabilities and on recent literature addressing secondary
      prevention for specific cardioembolic sources, upon which diagnosis and prognosis
      primarily depend. While early evaluation with modern neuroimaging techniques
      offers to enhance diagnostic accuracy, additional study is required to define
      optimal utilization. Appropriate imaging of the heart and aorta is paramount to
      identifying potential sources of embolism. Secondary prevention for high-risk
      embolic sources generally involves anticoagulation, but immediate initiation of
      anticoagulation is not routinely indicated. Medium-risk sources have more modest
      or undefined risks and little randomized comparative evidence to guide
      management, but antiplatelet therapy is generally favored. One possible exception
      is patent foramen ovale, for which high-risk features may warrant anticoagulation
      or mechanical closure. Definitive recommendations for this and other findings
      await completion of ongoing clinical trials.

PMID- 18342222
TI  - Direct stenting for stable angina pectoris is associated with reduced
      periprocedural microcirculatory injury compared with stenting after pre-dilation.
AB  - OBJECTIVES: We conducted a randomized study to compare the effect of direct
      stenting (DS) and conventional stenting (CS) on post-procedural index of
      microcirculatory resistance (IMR) values. BACKGROUND: Direct stenting has been
      suggested to reduce periprocedural microcirculatory injury compared with stenting
      that follows pre-dilation (CS). The index of microcirculatory resistance is a
      sensitive invasive marker of coronary microvascular resistance. METHODS: Fifty
      patients admitted for elective percutaneous coronary intervention (PCI) were
      included. All patients had stable angina (Canadian Cardiovascular Society class
      <IV) related to a lesion suitable for DS and were randomized to DS (n = 25) or CS
      (n = 25). Baseline demographics and clinical and procedural data were comparable
      in both groups. An intracoronary pressure/temperature sensor-tipped guide wire
      was used. Thermodilution curves were obtained at baseline and during maximal
      hyperemia achieved by infusion of intravenous adenosine. The index of
      microcirculatory resistance was calculated from the ratio of the mean distal
      coronary pressure at maximal hyperemia to the inverse of mean hyperemic transit
      time. RESULTS: After otherwise-uneventful PCI, patients treated with CS had
      significantly greater IMR (DS 13 +/- 3, CS 24 +/- 14; p < 0.01) and tended to
      have greater post-PCI troponin T values (DS 0.035 +/- 0.04, CS 0.17 +/- 0.02; p =
      0.07). In the whole sample, 20% of patients had post-PCI troponin release
      (troponin T >0.03 ng/ml). Patients with troponin elevation had significantly
      greater post-PCI IMR values than patients without troponin elevation: 24.7 +/-
      13.2 versus 16.9 +/- 10.2; p = 0.04. CONCLUSIONS: In patients undergoing
      successful coronary stenting for stable angina, DS is associated with reduced
      microvascular dysfunction induced by PCI as compared with CS.

PMID- 18342223
TI  - Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than
      conventional regimens: results from the PREPAIR randomized study.
AB  - OBJECTIVES: The objective of this study was to compare the level of platelet
      inhibition achieved by 3 different clopidogrel loading regimens in patients
      undergoing elective angiography and percutaneous coronary intervention when
      appropriate. BACKGROUND: Optimal platelet inhibition is a key therapeutic goal
      for patients undergoing percutaneous coronary intervention. Although 600 mg has
      been described as the maximum absorbed dose when given as a single bolus, the
      effects of 2 boluses given 24 h apart have not been described. METHODS: Patients
      (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300
      mg the day before (>or=15 h) + 75 mg the morning of the procedure; Group B,
      clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C,
      clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the
      procedure (>or=2 h). Blood samples were obtained at baseline and immediately
      before angiography. Peak and late platelet aggregation were measured in platelet
      rich plasma, with researchers blinded to treatment allocation. RESULTS: There was
      a consistent difference favoring Group C in all aggregation parameters. Percent
      inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for
      peak aggregation (5 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%,
      57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar
      striking reductions were observed when 20 micromol/l adenosine diphosphate was
      used. All comparisons between Group C and the other 2 groups were statistically
      significant, and those between Groups A and B were not. CONCLUSIONS: Clopidogrel
      600-mg double bolus achieves greater platelet inhibition than conventional single
      loading doses.

PMID- 18342224
TI  - Randomized controlled trial of an implantable continuous hemodynamic monitor in
      patients with advanced heart failure: the COMPASS-HF study.
AB  - OBJECTIVES: The purpose of this study was to determine whether a heart failure
      (HF) management strategy using continuous intracardiac pressure monitoring could
      decrease HF morbidity. BACKGROUND: Patients with HF may experience frequent
      decompensations that require hospitalization despite intensive treatment and
      follow-up. METHODS: The COMPASS-HF (Chronicle Offers Management to Patients with
      Advanced Signs and Symptoms of Heart Failure) study was a prospective,
      multicenter, randomized, single-blind, parallel-controlled trial of 274 New York
      Heart Association functional class III or IV HF patients who received an
      implantable continuous hemodynamic monitor. Patients were randomized to a
      Chronicle (Medtronic Inc., Minneapolis, Minnesota) (n = 134) or control (n = 140)
      group. All patients received optimal medical therapy, but the hemodynamic
      information from the monitor was used to guide patient management only in the
      Chronicle group. Primary end points included freedom from system-related
      complications, freedom from pressure-sensor failure, and reduction in the rate of
      HF-related events (hospitalizations and emergency or urgent care visits requiring
      intravenous therapy). RESULTS: The 2 safety end points were met with no pressure
      sensor failures and system-related complications in only 8% of the 277 patients
      who underwent implantation (all but 4 complications were successfully resolved).
      The primary efficacy end point was not met because the Chronicle group had a
      nonsignificant 21% lower rate of all HF-related events compared with the control
      group (p = 0.33). A retrospective analysis of the time to first HF
      hospitalization showed a 36% reduction (p = 0.03) in the relative risk of a HF
      related hospitalization in the Chronicle group. CONCLUSIONS: The implantable
      continuous hemodynamic monitor-guided care did not significantly reduce total HF
      related events compared with optimal medical management. Additional trials will
      be necessary to establish the clinical benefit of implantable continuous
      hemodynamic monitor-guided care in patients with advanced HF.

PMID- 18342225
TI  - Learning the points of COMPASS-HF: assessing implantable hemodynamic monitoring
      in heart failure patients.

PMID- 18342226
TI  - Prolonged signal-averaged P-wave duration as an intermediate phenotype for
      familial atrial fibrillation.
AB  - OBJECTIVES: This study sought to perform a genome-wide linkage analysis in a
      large atrial fibrillation (AF) kindred using AF and abnormally prolonged signal
      averaged (SA) P-wave duration as the phenotype. BACKGROUND: Although inherited
      forms of AF exist, phenotypic complexity has limited efforts to ascertain
      mutation carriers and thus identify causal genes. The identification of
      intermediate or endophenotypes may accelerate this effort. METHODS: A genome-wide
      linkage analysis was performed in a 4-generation AF kindred of 27 individuals, 8
      with AF documented by electrocardiogram. The analysis was performed using AF as
      the phenotype, and repeated using an abnormally prolonged SA P-wave duration as
      the phenotype. RESULTS: Linkage analysis and fine mapping generated a maximum
      multipoint logarithm of the odds (LOD) score of 3.0 at chromosome 5p15 between
      markers D5S406 and D5S635. Importantly, 8 heterozygous carriers had a prolonged
      SA P-wave (203 +/- 21 ms) compared with 17 noncarriers (116 +/- 12 ms, p <
      0.00001). Using prolonged SA P-wave (conventionally defined as >155 ms) as an
      endophenotype, a maximum LOD score of 3.6 was obtained in the same region of
      chromosome 5p15, a span of 5.75 centi-Morgans. CONCLUSIONS: In a large AF
      kindred, we have identified a novel AF locus on chromosome 5p15 and shown that
      affected individuals with AF and mutation carriers can be identified by a
      prolonged SA P-wave duration. Importantly, identification of an endophenotype in
      this kindred not only aided ascertainment of additional family members but also
      increased the LOD score, providing increased support for linkage at this locus.
      Identification of the causal gene, mapped to chromosome 5p15, will advance our
      understanding of the molecular basis of AF.

PMID- 18342227
TI  - An irregularly irregular inheritance.

PMID- 18342228
TI  - Pre-operative N-terminal pro-brain natriuretic peptide predicts outcome in type A
      aortic dissection.
AB  - BACKGROUND: Acute Stanford type A aortic dissection (AAD) is associated with
      substantial perioperative mortality and morbidity. OBJECTIVE: N-terminal pro
      brain natriuretic peptide (NT-proBNP) is a prognostic biomarker of outcome in
      cardiovascular disease. Its predictive power in patients undergoing emergency
      surgery for acute type A aortic dissection is yet unknown. METHODS: We
      prospectively measured pre-operative NT-proBNP in 104 patients (39 female, 35%;
      median age 61 years) undergoing emergency surgery for AAD during a 6-year study
      period. European System for Cardiac Operative Risk Evaluation risk scores were
      recorded and patients were followed for 30-day mortality and major adverse events
      (MAEs) as defined by the need for rethoracotomy, occurrence of postoperative
      heart failure, neurologic deficit, lung failure, renal failure, or sepsis.
      RESULTS: Median logistic European System for Cardiac Operative Risk Evaluation in
      the cohort was 12 (interquartile range 7 to 19). During the first 30 days, 23
      patients (22%) died, and 53 patients (51%) experienced MAEs. Median
      (interquartile range) NT-proBNP levels in survivors versus nonsurvivors were 328
      pg/ml (157 to 569) versus 2,240 pg/ml (515 to 4,734; p < 0.001), and in patients
      without versus with MAEs, 227 pg/ml (107 to 328) and 719 pg/ml (442 to 2,287; p <
      0.001), respectively. Adjusted odds ratios for increasing tertiles of NT-proBNP
      compared with the lowest tertile were 0.98 (95% confidence interval [CI] 0.18 to
      5.33; p = 0.98) and 11.67 (95% CI 2.61 to 52.09; p = 0.001) for 30-day mortality
      and 9.07 (95% CI 2.58 to 31.83; p = 0.001) and 50.21 (95% CI 10.85 to 232.45; p <
      0.001) for MAEs, respectively, indicating a significant association between pre
      operative NT-proBNP levels and outcome. CONCLUSIONS: Pre-operative NT-proBNP
      predicts outcome in patients undergoing surgery of AAD.

PMID- 18342229
TI  - Dose-related effects of repeated ETC-216 (recombinant apolipoprotein A-I Milano/1
      palmitoyl-2-oleoyl phosphatidylcholine complexes) administrations on rabbit lipid
      rich soft plaques: in vivo assessment by intravascular ultrasound and magnetic
      resonance imaging.
AB  - OBJECTIVES: This study sought to evaluate in vivo the minimal dose of
      apolipoprotein (apo) A-I(Milano) phospholipid complex (recombinant apoA-I(Milano)
      and 1-palmitoyl-2-oleoyl phosphatidylcholine complexes [ETC-216]) able to induce
      atherosclerosis regression in a rabbit model of lipid-rich plaques. BACKGROUND: A
      single high dose of recombinant apoA-I(Milano) has promoted atherosclerosis
      regression in animal models. More recently, regression of atherosclerosis was
      achieved in coronary patients by repeated infusions of ETC-216. METHODS: Thirty
      six rabbits underwent perivascular injury at both carotid arteries, followed by a
      1.5% cholesterol diet. After 90 days, rabbits were randomly divided into 6 groups
      and treated 5 times with vehicle or ETC-216 at 5, 10, 20, 40, or 150 mg/kg dose
      every 4 days. Carotid plaque changes were evaluated in vivo by intravascular
      ultrasound (IVUS) and magnetic resonance imaging (MRI), performed before and at
      the end of treatments. Magnetic resonance imaging scans were also recorded after
      administration of the second dose for rabbits infused with vehicle 40 or 150
      mg/kg. RESULTS: Atheroma volume in vehicle-treated rabbits increased dramatically
      between the first and the second IVUS analyses (+26.53%), whereas in ETC-216
      treated animals, a reduced progression at the lower doses and a significant
      regression at the higher doses, up to -6.83%, was detected. Results obtained by
      MRI analysis correlated significantly with those at IVUS (r = 0.706; p < 0.0001).
      The MRI evaluations after the second infusion established that a significant
      regression was achieved with only 2 administrations of the highest dose.
      CONCLUSIONS: These results confirm the efficacy of ETC-216 for atherosclerosis
      treatment and provide guidance for dose selection and frequency to obtain a
      significant reduction of plaque volume.

PMID- 18342230
TI  - Rapid change in plaque size, composition, and molecular footprint after
      recombinant apolipoprotein A-I Milano (ETC-216) administration: magnetic
      resonance imaging study in an experimental model of atherosclerosis.
AB  - OBJECTIVES: This study sought to assess the effect of short-term apolipoprotein
      (apo) A-I(Milano) administration on plaque size and on suspected markers of
      plaque vulnerability. BACKGROUND: Long-term lipid-lowering interventions can
      regress and stabilize atherosclerotic plaques. However, the majority of recurrent
      events occur early after the first episode. Interventions able to acutely induce
      plaque regression and stabilization are lacking. Regression of human coronary
      lesions after 5 weeks of treatment with apoA-I(Milano) administration has been
      shown. However, there are no data regarding its effect on plaque vulnerability.
      METHODS: Advanced aortic lesions were induced in New Zealand White rabbits (n =
      40). Plaque size was assessed by magnetic resonance imaging (MRI) at the end of
      atherosclerosis induction. Animals were randomized to placebo or apoA-I(Milano)
      phospholipids (ETC-216), 2 infusions 4 days apart. After the last dose, another
      MRI study was performed and aortas were processed for cellular composition and
      gene protein expression of markers associated with plaque instability. RESULTS:
      Pre-treatment MRI showed similar plaque size in both groups, whereas post
      treatment MRI showed 6% smaller plaques in apoA-I(Milano)-treated animals
      compared with placebo (p = 0.026). The apoA-I(Milano) treatment induced a 5%
      plaque regression (p = 0.003 vs. pre-treatment), whereas the placebo showed no
      significant effect. Plaque regression by apoA-I(Milano) was associated with a
      reduction in plaque macrophage density and a significant down-regulation in gene
      and protein expression of tissue factor, monocyte chemoattractant protein-1, and
      cyclooxygenase-2, as well as marked decrease in gelatinolytic activity.
      Conversely, cyclooxygenase-1 was significantly up-regulated. CONCLUSIONS: Acute
      plaque regression observed after short-term apoA-I(Milano) administration was
      associated with a significant reduction in suspected makers of plaque
      vulnerability in an experimental model of atherosclerosis.

PMID- 18342231
TI  - ApoA-I(Milano)/phospholipid complex: clinical implications of dose-response
      studies in rabbit atherosclerosis with intravascular ultrasound and magnetic
      resonance imaging.

PMID- 18342232
TI  - Reversal of cardiac dysfunction after long-term expression of SERCA2a by gene
      transfer in a pre-clinical model of heart failure.
AB  - OBJECTIVES: The aim of this study was to examine the effects of sarcoplasmic
      reticulum Ca(2+) ATPase (SERCA2a) gene transfer in a swine heart failure (HF)
      model. BACKGROUND: Reduced expression and activity of SERCA2a have been
      documented in HF. Prior studies have reported the beneficial effects of short
      term SERCA2a overexpression in rodent models. However, the effects of long-term
      expression of SERCA2a in pre-clinical large animal models are not known. METHODS:
      Yorkshire-Landrace pigs were used (n = 16) to create volume overload by
      percutaneously severing chordae tendinae of the mitral apparatus with a bioptome
      to induce mitral regurgitation. At 2 months, pigs underwent intracoronary
      delivery of either recombinant adeno-associated virus type 1 (rAAV1) carrying
      SERCA2a under a cytomegalovirus promoter (rAAV1.SERCA2a) (n = 10; group 1) or
      saline (n = 6; group 2). RESULTS: At 2 months, study animals were found to be in
      a compensated state of volume-overload HF (increased left ventricular internal
      diastolic and systolic diameters [LVIDd and LVIDs]). At 4 months, gene transfer
      resulted in: 1) positive left ventricular (LV) inotropic effects (adjusted peak
      left ventricular pressure rate of rise (dP/dt)max/P, 21.2 +/- 3.2 s(-1) group 1
      vs. 15.5 +/- 3.0 s(-1) group 2; p < 0.01); 2) improvement in LV remodeling (%
      change in LVIDs -3.0 +/- 10% vs. +15 +/- 11%, respectively; p < 0.01). At follow
      up, brain natriuretic peptide levels remained stable in group 1 after gene
      transfer, in contrast to rising levels in group 2. Further, cardiac SERCA2a
      expression was significantly decreased in group 2 whereas in group 1 it was
      restored to normal levels. There was no histopathological evidence of acute
      myocardial inflammation or necrosis. CONCLUSIONS: Using a large-animal, volume
      overload model of HF, we report that long-term overexpression of SERCA2a by in
      vivo rAAV1-mediated intracoronary gene transfer preserved systolic function,
      potentially prevented diastolic dysfunction, and improved ventricular remodeling.

PMID- 18342233
TI  - Clinical trials and clinical judgment.

PMID- 18342235
TI  - Fractional flow reserve-guided intervention of angiographically nonsignificant
      coronary stenoses.

PMID- 18342236
TI  - Drug-eluting stent implantation may not affect vasomotor function in early phase.

PMID- 18342237
TI  - Early detection of rheumatic heart disease and prevention of heart failure in sub
      Saharan Africa.

PMID- 18342241
TI  - Genetic and environmental modulation of postprandial lipemia: from a better
      knowledge of the mechanisms to a more effective treatment strategy.

PMID- 18342240
TI  - ACCF/ASE/ACEP/AHA/ASNC/SCAI/SCCT/SCMR 2008 appropriateness criteria for stress
      echocardiography: a report of the American College of Cardiology Foundation
      Appropriateness Criteria Task Force, American Society of Echocardiography,
      American College of Emergency Physicians, American Heart Association, American
      Society of Nuclear Cardiology, Society for Cardiovascular Angiography and
      Interventions, Society of Cardiovascular Computed Tomography, and Society for
      Cardiovascular Magnetic Resonance endorsed by the Heart Rhythm Society and the
      Society of Critical Care Medicine.
AB  - The American College of Cardiology Foundation (ACCF) and the American Society of
      Echocardiography (ASE) together with key specialty and subspecialty societies,
      conducted an appropriateness review for stress echocardiography. The review
      assessed the risks and benefits of stress echocardiography for several
      indications or clinical scenarios and scored them on a scale of 1 to 9 (based
      upon methodology developed by the ACCF to assess imaging appropriateness). The
      upper range (7 to 9) implies that the test is generally acceptable and is a
      reasonable approach, and the lower range (1 to 3) implies that the test is
      generally not acceptable and is not a reasonable approach. The midrange (4 to 6)
      indicates a clinical scenario for which the indication for a stress
      echocardiogram is uncertain. The indications for this review were drawn from
      common applications or anticipated uses, as well as from current clinical
      practice guidelines. Use of stress echocardiography for risk assessment in
      patients with coronary artery disease (CAD) was viewed favorably, while routine
      repeat testing and general screening in certain clinical scenarios were viewed
      less favorably. It is anticipated that these results will have a significant
      impact on physician decision making and performance, reimbursement policy, and
      will help guide future research.

PMID- 18342242
TI  - Secondary structure of ITS2 rRNA provides taxonomic characters for systematic
      studies--a case in Lycoperdaceae (Basidiomycota).
AB  - The secondary structure of the ITS2 rDNA transcript (pre-rRNA) could provide
      information for identifying homologous nucleotide characters useful for cladistic
      inference of relationships. Such structure data could become taxonomic
      characters. This work compares the effect of several modern nucleotide alignment
      strategies, including those making use of structure data, on phylogenetic
      inference. From both the phylogenetic analyses and comparative secondary
      structure, implications for taxonomy and evolution of puffball fungi are
      discussed. Lycoperdaceae remain insufficiently resolved with present taxon and
      data sampling. Neither alignment allows statistically robust phylogenetic
      hypotheses under any current optimality criterion. The secondary structure data
      at this time are best used as accessory taxonomic characters as their
      phylogenetic resolving power and confidence in validity is limited compared with
      underlying nucleotide characters. We introduce a preliminary nomenclature
      convention to describe secondary structure for defining consensus features. These
      consensus structures are illustrated for the clades /Calvatia, /Handkea
      Echinatum, /Vascellum, /Morganella, and /Plumbea-Paludosa (Bovista).

PMID- 18342243
TI  - The beetle by the name of Tribolium typology and etymology of Tribolium castaneum
      Herbst, 1797. Introduction.

PMID- 18342244
TI  - Analysis of transcriptome data in the red flour beetle, Tribolium castaneum.
AB  - The whole genome sequence of Tribolium castaneum, a worldwide coleopteran pest of
      stored products, has recently been determined. In order to facilitate accurate
      annotation and detailed functional analysis of this genome, we have compiled and
      analyzed all available expressed sequence tag (EST) data. The raw data consist of
      61,228 ESTs, including 10,704 obtained from NCBI and an additional 50,524 derived
      from 32,544 clones generated in our laboratories. These sequences were amassed
      from cDNA libraries representing six different tissues or stages, namely: whole
      embryos, whole larvae, larval hindguts and Malpighian tubules, larval fat bodies
      and carcasses, adult ovaries, and adult heads. Assembly of the 61,228 sequences
      collapsed into 12,269 clusters (groups of overlapping ESTs representing single
      genes), of which 10,134 mapped onto 6,463 (39%) of the 16,422 GLEAN gene models
      (i.e. official Tribolium gene list). Approximately 1,600 clusters (13% of the
      total) lack corresponding GLEAN models, despite high matches to the genome,
      suggesting that a considerable number of transcribed sequences were missed by the
      gene prediction programs or were removed by GLEAN. We conservatively estimate
      that the current EST set represents more than 7,500 transcription units.

PMID- 18342245
TI  - The red flour beetle's large nose: an expanded odorant receptor gene family in
      Tribolium castaneum.
AB  - The Tribolium castaneum genome sequence reveals a large number of odorant
      receptor (Or) genes compared to those found in other insects whose olfactory
      genomes have been studied-341 Or genes and pseudogenes, encoding 259 intact
      odorant receptor proteins. An RT-PCR study of larvae and adults revealed that
      only 145 (64%) of 233 genes with successful genomic DNA amplifications were
      expressed. No expression of the other 87 genes was detected at any age,
      suggesting either that these genes are not expressed in this particular strain,
      or that they are induced only in certain environmental or developmental
      conditions. TcOR1, the ortholog of the Drosophila Or83b (DmOr83b) gene, which is
      required for the function of olfactory receptor proteins in Drosophila, was
      expressed in extracts from adult and larval heads and in extracts from adult
      bodies. Expression of 41 TcOr genes was detected in extracts from larval head
      tissue and 111 in extracts from adult head tissue (both figures exclude TcOr1).
      Twenty-eight TcOrs were detected only in adult bodies. Beetle pupae were injected
      with TcOr1 dsRNA; unlike sham-injected and control beetles, these knock-down
      beetles showed no significant response to the Tribolium aggregation pheromone,
      supporting the hypothesis that TcOr1 plays a similar decisive role in olfaction
      to DmOr83b. The substantial number of Ors poses the question of why Tribolium has
      such a large olfactory receptor repertoire, and underlines the need for more
      studies of the natural history of this species.

PMID- 18342246
TI  - The SNMP/CD36 gene family in Diptera, Hymenoptera and Coleoptera: Drosophila
      melanogaster, D. pseudoobscura, Anopheles gambiae, Aedes aegypti, Apis mellifera,
      and Tribolium castaneum.
AB  - Sensory neuron membrane proteins (SNMPs) are membrane bound proteins initially
      identified in olfactory receptor neurons of Lepidoptera and are thought to play a
      role in odor detection; SNMPs belong to a larger gene family characterized by the
      human protein CD36. We have identified 12-14 candidate SNMP/CD36 homologs from
      each of the genomes of Drosophila melanogaster, D. pseudoobscura, Anopheles
      gambiae and Aedes aegypti (Diptera), eight candidate homologs from Apis mellifera
      (Hymenoptera), and 15 from Tribolium castaneum (Coleoptera). Analysis (sequence
      similarity and intron locations) suggests that the insect SNMP/CD36 genes fall
      into three major groups. Group 1 includes the previously characterized D.
      melanogaster emp (epithelial membrane protein). Group 2 includes the previously
      characterized D. melanogaster croquemort, ninaD, santa maria, and peste. Group 3
      genes include the SNMPs, which fall into two subgroups referred to as SNMP1 and
      SNMP2. D. melanogaster SNMP1 (CG7000) shares both significant sequence similarity
      and five of its six intron insertion sites with the lepidopteran Bombyx mori
      SNMP1. The topological conservation of this gene family within the three major
      holometabolous lineages indicates that it predates the coleopteran and
      hymenoptera/dipera/lepidoptera split 300+ million years ago. The current state of
      knowledge of the characterized insect members of this gene family is discussed.

PMID- 18342247
TI  - Annotation of Tribolium nuclear receptors reveals an increase in evolutionary
      rate of a network controlling the ecdysone cascade.
AB  - The Tribolium genome contains 21 nuclear receptors, representing all of the six
      known subfamilies. This first complete set for a coleopteran species reveals a
      strong conservation of the number and identity of nuclear receptors in
      holometabolous insects. Two novelties are observed: the atypical NR0 gene knirps
      is present only in brachyceran flies, while the NR2E6 gene is found only in
      Tribolium and in Apis. Using a quantitative analysis of the evolutionary rate, we
      discovered that nuclear receptors could be divided into two groups. In one group
      of 13 proteins, the rates follow the trend of the Mecopterida genome-wide
      acceleration. In a second group of five nuclear receptors, all acting early
      during the ecdysone cascade, we observed an even higher increase of the
      evolutionary rate during the early divergence of Mecopterida. We thus extended
      our analysis to the 12 classic ecdysone transcriptional regulators and found that
      six of them (ECR, USP, HR3, E75, HR4 and Kr-h1) underwent an increase in
      evolutionary rate at the base of the Mecopterida lineage. By contrast, E74, E93,
      BR, HR39, FTZ-F1 and E78 do not show this divergence. We suggest that coevolution
      occurred within a network of regulators that control the ecdysone cascade. The
      advent of Tribolium as a powerful model should allow a better understanding of
      this evolutionary event.

PMID- 18342248
TI  - Identification and characterization of nuclear receptors from the red flour
      beetle, Tribolium castaneum.
AB  - Nuclear receptors (NRs) are classified by the presence of a well-conserved DNA
      binding domain and a less conserved ligand-binding domain and function as key
      control points in diverse signaling and metabolic pathways. NRs are switched on
      and off by small molecule ligands with properties similar to insecticides.
      Therefore, NRs are attractive targets for developing new insecticides. Nineteen
      canonical and two Knirps family NRs were identified in the genome of Tribolium
      castaneum. RNAi analysis showed that 10 out of the 19 canonical NRs, TcE75,
      TcHR3, TcHR4, TcEcR, TcUSP, TcFTZ-F1, TcHR51, SVP, TcHR38, TcHR39 are important
      for metamorphosis. Knocking down the expression of five NRs, TcTll, TcDsf, TcHNF4
      and TcHR78 caused defects in production of offspring. TcHNF4, TcHR78, TCHR51 and
      TcDsf affected egg production and TcTll affected embryonic development. Knocking
      down the expression of non-canonical NR Knirps-like affected adults and caused
      reduction in egg production. The other Knirps family member, Eagle, and five
      canonical NRs, TcE78, TcHR83, TcHR96, TcPNR-like and TcERR did not show much
      effect on metamorphosis or production of offspring. Quantitative real-time
      reverse transcriptase analysis showed that the mRNA levels of all NRs tested were
      reduced in DsRNA injected larvae when compared to their levels in control larvae
      injected with bacterial malE DsRNA suggesting that the RNAi worked well but
      reduction in expression levels of some of the NRs did not affect metamorphosis or
      production of offspring.

PMID- 18342249
TI  - Domain organization and phylogenetic analysis of proteins from the chitin
      deacetylase gene family of Tribolium castaneum and three other species of
      insects.
AB  - A bioinformatics investigation of four insect species with annotated genome
      sequences identified a family of genes encoding chitin deacetylase (CDA)-like
      proteins, with five to nine members depending on the species. CDAs (EC 3.5.1.41)
      are chitin-modifying enzymes that deacetylate the beta-1,4-linked N
      acetylglucosamine homopolymer. Partial deacetylation forms a heteropolysaccharide
      that also contains some glucosamine residues, while complete deacetylation
      produces the homopolymer chitosan, consisting exclusively of glucosamine. The
      genomes of the red flour beetle, Tribolium castaneum, the fruit fly, Drosophila
      melanogaster, the malaria mosquito, Anopheles gambiae, and the honey bee, Apis
      mellifera contain 9, 6, 5 and 5 genes, respectively, that encode proteins with a
      chitin deacetylase motif. The presence of alternative exons in two of the genes,
      TcCDA2 and TcCDA5, increases the protein diversity further. Insect CDA-like
      proteins were classified into five orthologous groups based on phylogenetic
      analysis and the presence of additional motifs. Group I enzymes include CDA1 and
      isoforms of CDA2, each containing in addition to a polysaccharide deacetylase
      like catalytic domain, a chitin-binding peritrophin-A domain (ChBD) and a low
      density lipoprotein receptor class A domain (LDLa). Group II is composed of CDA3
      orthologs from each insect species with the same domain organization as group I
      CDAs, but differing substantially in sequence. Group III includes CDA4s, which
      have the ChBD domain but do not have the LDLa domain. Group IV comprises CDA5s,
      which are the largest CDAs because of a very long intervening region separating
      the ChBD and catalytic domains. Among the four insect species, Tribolium is
      unique in having four CDA genes in group V, whereas the other insect genomes have
      either one or none. Most of the CDA-like proteins have a putative signal peptide
      consistent with their role in modifying extracellular chitin in both cuticle and
      peritrophic membrane during morphogenesis and molting.

PMID- 18342250
TI  - Domain organization and phylogenetic analysis of the chitinase-like family of
      proteins in three species of insects.
AB  - A bioinformatics-based investigation of three insect species with completed
      genome sequences has revealed that insect chitinase-like proteins
      (glycosylhydrolase family 18) are encoded by a rather large and diverse group of
      genes. We identified 16, 16 and 13 putative chitinase-like genes in the genomic
      databases of the red flour beetle, Tribolium castaneum, the fruit fly, Drosophila
      melanogaster, and the malaria mosquito, Anopheles gambiae, respectively.
      Chitinase-like proteins encoded by this gene family were classified into five
      groups based on phylogenetic analyses. Group I chitinases are secreted proteins
      that are the most abundant such enzymes in molting fluid and/or integument, and
      represent the prototype enzyme of the family, with a single copy each of the
      catalytic domain and chitin-binding domain (ChBD) connected by an S/T-rich linker
      polypeptide. Group II chitinases are unusually larger-sized secreted proteins
      that contain multiple catalytic domains and ChBDs. Group III chitinases contain
      two catalytic domains and are predicted to be membrane-anchored proteins. Group
      IV chitinases are the most divergent. They usually lack a ChBD and/or an S/T-rich
      linker domain, and are known or predicted to be secreted proteins found in gut or
      fat body. Group V proteins include the putative chitinase-like imaginal disc
      growth factors (IDGFs). In each of the three insect genomes, multiple genes
      encode group IV and group V chitinase-like proteins. In contrast, groups I-III
      are each represented by only a singe gene in each species.

PMID- 18342251
TI  - Characterization of recombinant chitinase-like proteins of Drosophila
      melanogaster and Tribolium castaneum.
AB  - Insect chitinase (CHT) family proteins are encoded by as many as 16 genes
      depending upon the species of interest. We have classified these proteins in
      three species into five different groups based on amino acid sequence
      similarities (Zhu et al., companion paper). The functions of most of the
      individual proteins of this family during growth and development are largely
      unknown. To help determine their enzymatic properties and physiological roles, we
      expressed representative members belonging to this protein family from Drosophila
      melanogaster (Dm) and Tribolium castaneum (Tc), and characterized their kinetic
      and carbohydrate-binding properties. Seven proteins, including DmCHT 4, 5, 9 and
      DmDS47 from Drosophila, and TcCHT5, TcIDGF2 and TcIDGF4 from Tribolium, belonging
      to groups I, IV or V of the chitinase-like family were expressed in a baculovirus
      insect cell line expression system, purified and characterized. Their enzymatic
      and chitin-binding properties were compared to those of the well-characterized
      chitinase, MsCHT535, from Manduca sexta (Ms). All of these proteins, except those
      belonging to group V that are related to imaginal disc growth factors (IDGFs),
      exhibited chitinolytic activity against the long polymeric substrate, CM-Chitin
      RBV, and/or the short oligomeric substrate, MU-(GlcNAc)(3). TcCHT5, DmCHT5 and
      MsCHT535, which are members of group I chitinases, cleaved both polymeric and
      oligomeric substrates. Their enzymatic properties, including pH optima, kinetic
      parameters, and susceptibility to substrate inhibition by chitooligosaccharides,
      were similar. Two group IV chitinases, DmCHT4 and DmCHT9, also were
      characterized. DmCHT4 had one optimum pH of 6 towards the polymeric substrate and
      no detectable chitinolytic activity towards an oligosaccharide substrate. DmCHT9
      had high activity from pH 4 to 8 towards the polymeric substrate and exhibited
      low activity towards the oligosaccharide substrate. The group V proteins, TcIDGF2
      and TcIDGF4, contain all of the catalytically critical residues within conserved
      region II of family 18 chitinases but neither exhibited chitinolytic activity.
      Another group V protein, DmDS47, which lacks the critical glutamate residue in
      region II and the C-terminal CBD, also exhibited no chitinolytic activity.
      However, all three of the group V proteins bound to chitin tightly. A comparison
      of the amino acid sequences and homology model structures of group V proteins
      with enzymatically active members of the chitinase family indicated that the
      presence of additional loops of amino acids within the (betaalpha)(8)-barrel
      structure of these proteins interferes with productive substrate binding and/or
      catalysis.

PMID- 18342252
TI  - Characterization and expression of the beta-N-acetylhexosaminidase gene family of
      Tribolium castaneum.
AB  - Enzymes belonging to the beta-N-acetylhexosaminidase family cleave chitin
      oligosaccharides produced by the action of chitinases on chitin into the
      constituent N-acetylglucosamine monomer. Four genes encoding putative
      chitooligosaccharidolytic beta-N-acetylhexosaminidases (hereafter referred to as
      N-acetylglucosaminidases (NAGs)) in the red flour beetle, Tribolium castaneum,
      namely TcNAG1, TcFDL, TcNAG2, and TcNAG3, and three other related hexosaminidases
      were identified by searching the recently completed genome [Tribolium Genome
      Sequencing Consortium, 2007. The first genome sequence of a beetle, Tribolium
      castaneum, a model for insect development and pest biology. Nature, submitted for
      publication]. Full-length cDNAs for all four NAGs were cloned and sequenced, and
      the exon-intron organization of the corresponding genes was determined. Analyses
      of their developmental expression patterns indicated that, although all four of
      the NAGs are transcribed during most developmental stages, each gene had a
      distinct spatial and temporal expression pattern. TcNAG1 transcripts are the most
      abundant, particularly at the late pupal stage, while TcNAG3 transcripts are the
      least abundant, even at their peak levels in the late larval stages. The function
      of each NAG during different developmental stages was assessed by observations of
      lethal phenotypes after gene-specific double-stranded RNA (dsRNA)-mediated
      transcript depletion as verified by real-time PCR. TcNAG1 dsRNA was most
      effective in interrupting all three types of molts: larval-larval, larval-pupal,
      and pupal-adult. Treated insects died after failing to completely shed their old
      cuticles. Knockdown of transcripts for the other three NAG genes resulted in
      phenotypes similar to those of TcNAG1 dsRNA-treated insects, but the effects were
      somewhat variable and less severe. Sequence comparisons with other enzymatically
      characterized insect homologs suggested that TcFDL, unlike the other NAGs, may
      have a role in N-glycan processing in addition to its apparent role in cuticular
      chitin turnover. These results support the hypothesis that TcNAGs participate in
      chitin turnover and/or N-glycan processing during insect development and that
      each NAG fulfills an essential and distinct function.

PMID- 18342253
TI  - Large diversity of the piggyBac-like elements in the genome of Tribolium
      castaneum.
AB  - The piggyBac transposable element (TE), originally discovered in the cabbage
      looper, Trichoplusia ni, has been widely used in insect transgenesis including
      the red flour beetle Tribolium castaneum. We surveyed piggyBac-like (PLE)
      sequences in the genome of T. castaneum by homology searches using as queries the
      diverse PLE sequences that have been described previously. The search yielded a
      total of 32 piggyBac-like elements (TcPLEs) which were classified into 14
      distinct groups. Most of the TcPLEs contain defective functional motifs in that
      they are lacking inverted terminal repeats (ITRs) or have disrupted open reading
      frames. Only one single copy of TcPLE1 appears to be intact with imperfect 16bp
      ITRs flanking an open reading frame encoding a transposase of 571 amino acid
      residues. Many copies of TcPLEs were found to be inserted into or close to other
      transposon-like sequences. This large diversity of TcPLEs with generally low copy
      numbers suggests multiple invasions of the TcPLEs over a long evolutionary time
      without extensive multiplications or occurrence of rapid loss of TcPLEs copies.

PMID- 18342255
TI  - Genetic evaluation of intellectual disabilities.
AB  - All children with an intellectual disability (mental retardation) or global
      developmental delay should have a comprehensive evaluation to establish the
      etiology of the disability. A specific etiologic diagnosis offers the opportunity
      to discuss treatment, prognosis, and genetic recurrence risk. A diagnosis also
      avoids unnecessary testing and can lead to opportunities for improved health and
      functional outcomes. The key elements of the diagnostic evaluation are the
      medical and developmental history, 3-generation family history, dysmorphologic
      examination, neurologic examination, and judicious use of the laboratory and
      neuroimaging. All published guidelines for the evaluation of children with
      intellectual disability acknowledge that there is a substantial percentage of
      patients who are undiagnosed after a comprehensive evaluation and who deserve
      ongoing follow-up for the purpose of establishing a diagnosis. Recently, studies
      of the clinical application of array comparative genomic hybridization (aCGH) to
      individuals with intellectual disability indicate that this approach provides a
      diagnosis in as much as 10% of patients and that this technique is replacing the
      use of fluorescent in situ hybridization for subtelomere imbalances now used for
      such patients when the standard karyotype is normal. The literature suggests that
      history and examination by an expert clinician will lead to a diagnosis in 2 of 3
      patients in whom a diagnosis is made. Laboratory studies alone, including
      neuroimaging, provide a diagnosis in the remaining one third. The approach to the
      evaluation of the patient in whom an etiologic diagnosis is not suspected after
      the history and physical examinations includes a standard karyotype, Fragile X
      molecular genetic testing, aCGH, and neuroimaging, based on the evidence to date.
      One can expect rapid changes in the microarray technology in the near future.

PMID- 18342256
TI  - The evaluation of the hypotonic infant.
AB  - The pediatric neurologist is regularly asked to evaluate a hypotonic patient.
      This consultation request usually occurs in 2 different situations; the first is
      in the newborn period when the neurologist is asked to evaluate the "floppy
      infant," and the second is in the latter half of the first year of life and is
      usually accompanied by concern about the developmental progress of the infant
      and, in particular, the motor development of the infant. In this article, I will
      try to outline the factors related to the production of muscle tone in infants
      and children. The elements of the clinical evaluation of the hypotonic child
      including those clinical tests most helpful in the measurement of tone will be
      reviewed. A scheme for localizing the origin of the disturbance in muscle tone is
      presented, many of the known causes of the tone abnormalities are reviewed, and a
      rational approach to the diagnostic evaluation of these children is offered.

PMID- 18342257
TI  - Genetics considerations in cerebral palsy.
AB  - Cerebral palsy refers to a collective of neurologic conditions that share in
      common disorders of motor function and posture. Traditionally, and still today in
      many circles, the term is considered almost synonymous with brain injury.
      Multiple lines of evidence, however, point to the fact that cerebral palsy is
      rarely caused by problems with perinatal management. In fact, a mounting body of
      evidence points to strong genetic influences on the occurrence of cerebral palsy.
      Like most neurogenetic conditions, cerebral palsy exhibits complex inheritance.
      The best descriptor of the inheritance of cerebral palsy would be that of
      "multifactorial inheritance." This implies etiologic and genetic heterogeneity
      with complex interactions with multiple environmental influences. This article
      reviews known genetic influences on the origin of cerebral palsy. A proposed
      scheme for the genetic evaluation in identifying the etiology of cerebral palsy
      is provided.

PMID- 18342258
TI  - Genetic evaluation of autism.
AB  - The autism spectrum disorders represent a collective of neurogenetic conditions
      that have in common altered socialization and communication. Much attention has
      been given lately to the marked increased in the reported incidence of these
      conditions. Significant debate also exists as to the basis of the reported
      increase. Regardless, clinical geneticists and pediatric neurologists alike are
      seeing a tremendous increase in the number of referrals for autism and related
      conditions. Continuing advances in genetic testing provide a moving target for
      the clinician in determining an appropriate diagnostic plan. In this article, we
      review the most recent advances in genetic testing technology and their potential
      application to the etiologic evaluation of patients with autism spectrum
      disorders.

PMID- 18342259
TI  - The Hitchhiker's guide to the child neurologist's genetic evaluation of epilepsy.
AB  - Over the past several decades, familial aggregation studies as well as twin
      studies have supported a genetic component to seizures. The recent advent of the
      genome project has served as a catalyst in the search for elucidating the
      hereditary influences of various epilepsies. Overlapping seizure features may
      lead to ambiguity when attempting to isolate a single phenotype. Conversely, the
      phenomenon of genetic heterogeneity implies that multiple genetic mutations may
      give rise to a similar phenotype. Despite valiant attempts at strictly defining
      epilepsy phenotype and mode of penetrance, one must also consider the role of
      environment in gene expression. Genetics (testing) in epilepsy is no longer
      limited to the idiopathic epilepsies but may have an equally significant role in
      the symptomatic epilepsies. This article guides the reader through the genetics
      of epilepsy via discussion of the phenotypic description of known genetic
      childhood epilepsy syndromes, illustration of the associated gene mutations
      identified thus far, and the implications of genetic testing in clinical
      practice.

PMID- 18342260
TI  - Excessive daytime sleepiness: population and etiology versus nosology.

PMID- 18342261
TI  - From wakefulness to excessive sleepiness: what we know and still need to know.
AB  - The epidemiological study of hypersomnia symptoms is still in its infancy; most
      epidemiological surveys on this topic were published in the last decade. More
      than two dozen representative community studies can be found. These studies
      assessed two aspects of hypersomnia: excessive quantity of sleep and sleep
      propensity during wakefulness excessive daytime sleepiness. The prevalence of
      excessive quantity of sleep when referring to the subjective evaluation of sleep
      duration is around 4% of the population. Excessive daytime sleepiness has been
      mostly investigated in terms of frequency or severity; duration of the symptom
      has rarely been investigated. Excessive daytime sleepiness occurring at least 3
      days per week has been reported in between 4% and 20.6% of the population, while
      severe excessive daytime sleepiness was reported at 5%. In most studies, men and
      women are equally affected. In the International Classification of Sleep
      Disorders, hypersomnia symptoms are the essential feature of three disorders:
      insufficient sleep syndrome, hypersomnia (idiopathic, recurrent or posttraumatic)
      and narcolepsy. Insufficient sleep syndrome and hypersomnia diagnoses are poorly
      documented. The co-occurrence of insufficient sleep and excessive daytime
      sleepiness has been explored in some studies and prevalence has been found in
      around 8% of the general population. However, these subjects often have other
      conditions such as insomnia, depression or sleep apnea. Therefore, the prevalence
      of insufficient sleep syndrome is more likely to be between 1% and 4% of the
      population. Idiopathic hypersomnia would be rare in the general population with
      prevalence, around 0.3%. Narcolepsy has been more extensively studied, with a
      prevalence around 0.045% in the general population. Genetic epidemiological
      studies of narcolepsy have shown that between 1.5% and 20.8% of narcoleptic
      individuals have at least one family member with the disease. The large variation
      is mostly due to the method used to collect the information on the family
      members; systematic investigation of all family members provided higher results.
      There is still a lot to be done in the epidemiological field of hypersomnia.
      Inconsistencies in its definition and measurement limit the generalization of the
      results. The use of a single question fails to capture the complexity of the
      symptom. The natural evolution of hypersomnia remains to be documented.

PMID- 18342262
TI  - Social insect histology from the nineteenth century: the magnificent pioneer
      sections of Charles Janet.
AB  - Charles Janet (1849-1932) was the leading pioneer in the histological description
      of the internal anatomy of social insects, in particular of ants and wasps.
      Because many of the original Janet sections still exist, this article is able to
      illustrate the amazing skills through some selected pictures taken from this more
      than a century old material, and thus to pay tribute to this French founder of
      insect morphology.

PMID- 18342263
TI  - Comparison of spermatheca morphology between reproductive and non-reproductive
      females in social wasps.
AB  - Social wasps show an obvious evolution of the differentiation in behavior and
      external size between reproductive and non-reproductive females, with no clear
      differences in the Stenogastrinae, via overlap in the Polistinae, to clear
      differences in the Vespinae. In this study, we examined the morphological
      appearance of the spermatheca in representative species of these three
      subfamilies. The general anatomical organization of the spermatheca comprises a
      reservoir, a duct and two spermathecal glands, and is in line with its common
      structure in other social Hymenoptera. All examined wasp species have a
      spermathecal reservoir with uniform wall thickness, which is similar to the
      situation in the bees, but differentiates them from the ants. Within the wasps,
      the shape of the reservoir, the shape of the spermathecal glands and their
      attachment site to the spermatheca differs among the Stenogastrinae, Polistinae
      and Vespinae. The reservoir wall is thick in the Polistinae and Vespinae, while
      in the Stenogastrinae, it varies from thin in Parischnogaster to thick in
      Eustenogaster, with an intermediate situation in Liostenogaster. In all examined
      species, we found no differences in the spermathecal development between
      reproductive and non-reproductive wasps.

PMID- 18342264
TI  - Regeneration of the tibia and somatotopy of regenerated hair sensilla in
      Schistocerca gregaria (Forskal).
AB  - After injury many arthropods are able to regenerate lost body parts and their
      innervation. Here, regeneration was studied in the desert locust Schistocerca
      gregaria after amputation of the midleg tibia and tarsus in the first larval
      instar. A regenerate was formed first in the third larval instar and it increased
      in size with each larval moult. The regenerate was always unsegmented and
      remained much shorter than the intact leg parts. The growth rate was initially
      rather high and decreased thereafter to that of intact parts. The amputation also
      influenced the growth rate of proximal leg parts (femur and trochanter) resulting
      in shortened leg segments. The regenerate carried many sense organs like trichoid
      sensilla and canal sensilla. The primary mechanosensory neurons of the trichoid
      sensilla projected somatotopically into the mesothoracic ganglion. A comparison
      of these projections from intact leg segments and regenerates showed a regrow
      into the target neuropil areas and a restoration of the somatotopy. Intact
      sensilla on the injured leg and regenerated sensilla expanded their central
      projections lateral-medially.

PMID- 18342265
TI  - Limb articulation in caridoid crustaceans revisited - new evidence from
      Euphausiacea (Malacostraca).
AB  - The propodial articulation of thoracopods in Malacostraca is revisited. Two major
      joints at the base of the limb, a thorax-coxa joint and a coxa-basis joint permit
      promotion-remotion and abduction-adduction, respectively. In representatives of
      Decapoda, Anaspidacea and Euphausiacea, the coxa forms proximally a dicondylic
      articulation with the thorax, permitting promotion-remotion, and distally another
      dicondylic joint with the basis, permitting abduction-adduction. In Lophogastrida
      and Mysida, the thorax-coxa hinge line is antero-posteriorly oriented, as is the
      coxa-basis hinge line. Promotion-remotion in Mysida and Lophogastrida is possible
      because of the presence of an intrabasal joint which is also present in
      Euphausiacea and Anaspidacea. In Mysida, Lophogastrida and Euphausiacea, the
      intrabasal joint is only present anteriorly, just distally of the anterior coxa
      basis joint between a small, triangular proximal part of the basis and a larger
      distal part. In Anaspidacea, the intrabasal joint is also present posteriorly and
      permits abduction-adduction. Homology with the intrabasal joint of the other taxa
      seems doubtful. Limb articulation in Anaspidacea shows, nevertheless,
      correspondences with that in Euphausiacea, Lophogastrida and Mysida: the coxa is
      posteriorly invaginated and has an open ring-like structure very different from
      the solid coxa in decapods. Despite the high level of structural correspondence
      between the intrabasal joint in Euphausiacea and that in Lophogastrida and
      Mysida, their different functional roles make homology implausible. In
      Lophogastrida and Mysida the intrabasal joint is thought to replace the promotion
      remotion movement of the thorax-coxa articulation, which in these taxa permits
      abduction-adduction only, probably in connection with the evolution of the
      marsupium. In Euphausiacea, the intrabasal joint might play a role in feeding
      mechanisms. Neither the feeding basket nor a marsupium can reasonably be
      suggested for any common ancestor of Euphausiacea and Mysidacea (or Peracarida).

PMID- 18342266
TI  - Half-time for the Millennium Development Goals: time for travel medicine to enter
      the field.

PMID- 18342267
TI  - Communicable diseases in the immigrant population attended to in a tropical
      medicine unit: epidemiological aspects and public health issues.
AB  - For geographical and historical reasons, Spain is receiving an increasing number
      of immigrants. The aim of this study was to evaluate some epidemiological aspects
      and the main public health issues of communicable diseases in Barcelona's
      immigrant population. From 2001 to 2004, a population of immigrants from
      tropical, subtropical regions and Eastern Europe was attended to in our centre.
      Each patient was offered a complete screening for tropical and common diseases.
      The prevalence and demographical characteristics of eight diseases with a
      potential risk of transmission in our setting were studied: latent and active
      tuberculosis, syphilis, human immunodeficiency virus (HIV), hepatitis B virus
      (HBV) and hepatitis C virus (HCV), Chagas disease, Giardia intestinalis and
      Entamoeba histolytica/Entamoeba dispar. In all, 2464 immigrants mainly from sub
      Saharan Africa were seen. Among the patients who underwent the screening, 46.5%
      had a positive tuberculin skin test (>or=10 mm), incidence of active tuberculosis
      was 324.7/100,000 immigrants in the period of the study, 6.4% had a positive
      syphilis serology, 7.7% had a positive HBsAg, 3.1% had a positive serology for
      HCV and 2.8% were HIV positive, 41 patients from Latin America with risk factors
      for American Trypanosomiasis were screened for Chagas disease by
      immunofluorescence assay and 34% had a positive result; 5.4% of stools
      parasitological tests were positive for G. intestinalis; 4.2% for E.
      histolytica/E. dispar. Communicable diseases in immigrant population could lead
      to emerging and re-emerging infections in the European Union with important
      issues for public health. European countries may have to establish guidelines for
      screening of infectious diseases in immigrants from low-income countries.

PMID- 18342268
TI  - Assessment of rabies exposure risk among Israeli travelers.
AB  - BACKGROUND: The decision whether or not to administer rabies pre-exposure
      prophylaxis (PEP) to travelers visiting endemic areas is a complex one. Paramount
      for making that decision is knowledge of the risk of animal bites during travel.
      This study attempts to estimate the risk of bites in travelers, and study the
      action they took before and after the incident. METHODS: Travelers presenting for
      pre-travel immunizations during the period of August through December 2004, who
      planned a travel of >or= 1 month's duration were retrospectively identified,
      contacted and interviewed by a structured questionnaire. These travelers did not
      receive specific advice concerning rabies. RESULTS: The study cohort comprised of
      815 travelers (median age=25), of who 13 (1.6%) were injured by a potentially
      rabid animal (mainly, dog=6; monkey=4). The incidence of potential rabies
      exposure was found to be of 2.66 per 1000 travelers per month. Those injured had
      significantly longer trips than the non-injured (6.9+/-3.8 vs. 4+/-5.0 months,
      p=0.037); notably, the injuries occurred after a median of 5 weeks from
      departure. Although seven travelers noted blood at the site of injury, only four
      (31%) of the injured sought medical attention following the exposure, and all
      four received post-exposure prophylaxis. CONCLUSIONS: An injury by potentially
      rabid animals is not rare among long-term travelers. As the injury may occur
      early in the itinerary, rabies PEP should be considered for this population.
      Educational efforts are required in light of the lack of understanding of the
      dismal consequences of rabies among travelers.

PMID- 18342269
TI  - Jet lag: therapeutic use of melatonin and possible application of melatonin
      analogs.
AB  - Each year millions of travelers undertake long distance flights over one or more
      continents. These multiple time zone flights produce a constellation of symptoms
      known as jet lag. Familiar to almost every intercontinental traveler is the
      experience of fatigue upon arrival in a new time zone, but almost as problematic
      are a number of other jet lag symptoms. These include reduced alertness,
      nighttime insomnia, loss of appetite, depressed mood, poor psychomotor
      coordination and reduced cognitive skills, all symptoms which are closely
      affected by both the length and direction of travel. The most important jet lag
      symptoms are due to disruptions to the body's sleep/wake cycle. Clinical and
      pathophysiological studies also indicate that jet lag can exacerbate existing
      affective disorders. It has been suggested that dysregulation of melatonin
      secretion and occurrence of circadian rhythm disturbances may be the common links
      which underlie jet lag and affective disorders. Largely because of its regulatory
      effects on the circadian system, melatonin has proven to be highly effective for
      treating the range of symptoms that accompany transmeridian air travel.
      Additionally, it has been found to be of value in treating mood disorders like
      seasonal affective disorder. Melatonin acts on MT(1) and MT(2) melatonin
      receptors located in the hypothalamic suprachiasmatic nuclei, the site of the
      body's master circadian clock. Melatonin resets disturbed circadian rhythms and
      promotes sleep in jet lag and other circadian rhythm sleep disorders, including
      delayed sleep phase syndrome and shift-work disorder. Although post-flight
      melatonin administration works efficiently in transmeridian flights across less
      than 7-8 times zones, in the case longer distances, melatonin should be given by
      2-3 days in advance to the flight. To deal with the unwanted side effects which
      usually accompany this pre-departure treatment (acute soporific and sedative
      effects in times that may not be wanted), the suppression of circadian
      rhythmicity by covering symmetrically the phase delay and the phase advance
      portions of the phase response curve for light, together with the administration
      of melatonin at local bedtime to resynchronize the circadian oscillator, have
      been proposed. The current view that sleep loss is a major cause of jet lag has
      focused interest on two recently developed pharmacological agents. Ramelteon and
      agomelatine are melatonin receptor agonists which, compared to melatonin itself,
      have a longer half-life and greater affinity for melatonin receptors and
      consequently are thought to hold promise for treating a variety of circadian
      disruptions.

PMID- 18342270
TI  - Effectiveness of co-artemether in an unsupervised outpatient setting for the
      treatment of falciparum malaria.
AB  - OBJECTIVES: To assess artemether-lumefantrine effectiveness in the treatment of
      falciparum malaria in an unsupervised outpatient setting in Africa. DESIGN: Open
      label prospective study. SETTING: Occupational health clinic, Mozambique.
      SUBJECTS: Semi-immune Mozambican adults. OUTCOME MEASURES: 28-day treatment
      failures. RESULTS: 54/54 subjects were smear negative on day 2, and at 'day 28'
      (range 26-34 days). CONCLUSIONS: Artemether-lumefantrine is effective in semi
      immune adults in an unsupervised outpatient setting in Southern Africa, with no
      evidence of recrudescence.

PMID- 18342271
TI  - Klebsiella pneumoniae meningitis in a 38-year-old Chinese traveller with impaired
      glucose tolerance: a new emerging syndrome?
AB  - Early diagnosis and appropriate empirical treatment of bacterial meningitis
      reduce morbidity and mortality. Prevalence rates of different causative pathogens
      associated with bacterial meningitis can depend on age, the underlying medical
      condition, way of infection and geographical distribution. Klebsiella pneumoniae
      represents an infrequent cause of community-acquired meningitis in South-East
      Asia and North-East Asia, where it accounts for 20% of all bacterial meningitis,
      frequently associated with septic metastatic complications. We describe a case of
      K. pneumoniae meningitis, diplopia and chemosis in a recently immigrated patient
      with impaired glucose tolerance. The reason for the high prevalence of metastatic
      septic infections caused by K. pneumoniae in Taiwan and South-East Asia remains
      unclear: high prevalence in this area of serotype K1 and K2 and the expression of
      a novel locus called magA conferring to bacterium an elevated phagocytosis
      resistance and an active proliferation ability have been suggested. A high degree
      of suspicion for this etiology must be taken into account in immigrants from
      China and Taiwan. Due to a very high lethality, guidelines on empiric treatment
      should be considered in the management of bacterial meningitis, with the patients
      geographical origin and the clinical syndrome (meningitis and endophtalmitis) as
      potential risk factors for K. pneumoniae infection.

PMID- 18342272
TI  - A case of autochthonous Plasmodium vivax malaria, Corsica, August 2006.
AB  - A case of Plasmodium vivax malaria was diagnosed in Corsica in summer 2006. This
      is the first case of autochthonous transmission of malaria to be reported in
      Corsica since 1972. Corsica is a well-known malaria endemic region characterised,
      for several years now by an anophelism situation without malaria disease, due to
      the presence of An. labranchiae and An. saccharovi able to transmit P. vivax. The
      occurring sequence of malaria signs in an imported case on 9 July and in an
      autochthonous case on 5 August, both in Porto, implies a transmission by local
      Anopheles. This suspicion is reinforced by the results of entomological
      investigations. However, from June to September 2006, no other P. vivax malaria
      case and no other autochthonous case were detected in Corsica. Therefore, it
      seems that no permanent malaria transmission occurs in this island. Mosquito
      eradication actions and anti-vectorial measures have been reinforced as well as
      individual prevention measures against imported diseases while travelling in
      tropical countries. Obviously, detection of one exceptional autochthonous
      transmission of one malaria case in Corsica does not justify proposing malaria
      protection to tourists.

PMID- 18342273
TI  - Eosinophilic meningitis due to Angiostrongylus cantonensis in a Belgian
      traveller.
AB  - Eosinophilic meningitis is a rare clinical entity. The most frequent cause in
      travellers to the tropics is infection with the rat lungworm Angiostrongylus
      cantonensis. In this report, we describe a case of eosinophilic meningitis due to
      infection with this nematode in a traveller who presented with slight headache,
      diarrhoea, general malaise and thoracic radicular pain after a trip through Latin
      America and the Fiji Islands. She responded less than optimally to repeated
      steroid and albendazole treatments, but finally recovered completely.

PMID- 18342274
TI  - Extensive hookworm-related cutaneous larva migrans in Norwegian travellers to the
      tropics.
AB  - Hookworm-related cutaneous larva migrans is a common dermatosis in travellers to
      the tropics and typically presents as one or a few migrating serpiginous lesions
      on the lower extremities or buttocks. We present two Norwegian holidaymakers who
      developed extensive disease after returning from Brazil and Tanzania,
      respectively. Both patients responded to the treatment with ivermectin.

PMID- 18342275
TI  - Dengue maculopathy: was there also optic nerve involvement?

PMID- 18342276
TI  - Back to basics: from bench to bedside.

PMID- 18342277
TI  - New antimalarial targets: the example of glucose transport.
AB  - In order for a novel drug target to attract attention it must be shown to be
      essential for parasite survival. In addition, it is desirable that a novel target
      provides some molecular and functional basis for the development of selective
      inhibitors. In this respect the pathway for transport of glucose to the parasite
      in Plasmodium falciparum has attracted increasing interest as a target for
      antimalarial chemotherapy. In particular, the plasmodial hexose transporter,
      PfHT, known to mediate transport of this essential substrate to the parasite has
      been a promising candidate for development of inhibitors. The article summarises
      the steps involved in development of this parasite protein as a drug target.
      Details of PfHT identification, functional characterisation and its validation as
      a drug target by using a selective inhibitor are discussed. The potential use of
      a robust system to screen libraries of compounds in a high-throughput format, in
      pursuit of an inhibitor of PfHT is also described. In conclusion PfHT represents
      one example of a rational approach in the drug discovery process to structure
      base design of drugs.

PMID- 18342278
TI  - Understanding the role of inflammatory cytokines in malaria and related diseases.
AB  - It is now broadly accepted for infectious disease in general that it is not the
      invading organism, but the body's unbridled response to it--the "cytokine storm"-
      that causes illness and pathology. Nevertheless, many researchers still regard
      the harmful effects of falciparum malaria as being governed by oligaemic hypoxia
      arising from parasitised erythrocytes obstructing blood flow through vulnerable
      organs, particularly the brain, and we summarise why these notions are no longer
      tenable. In our view, this harmful sequestration is readily accommodated within
      the cytokine storm perspective as one of its secondary effects. We approach these
      issues by examining aspects of malaria, sepsis and influenza in parallel, and
      discuss the insights that comparisons of the literature can provide on the
      validity of possible anti-disease therapies.

PMID- 18342279
TI  - Molecular diagnostic and surveillance tools for global malaria control.
AB  - Malaria is the most devastating parasitic infection in the world, annually
      causing over 1 million deaths and extensive morbidity. The global burden of
      malaria has increased over the last several decades, as have rates of imported
      malaria into non-endemic regions. Rapid and accurate diagnostics are a crucial
      component of malaria control strategies, and epidemiological surveillance is
      required to monitor trends in malaria prevalence and antimalarial drug
      resistance. Conventional malaria diagnostic and surveillance tools can be
      cumbersome and slow with limitations in both sensitivity and specificity. New
      molecular techniques have been developed in an attempt to overcome these
      restrictions. These molecular techniques are discussed with regard to their
      technical advantages and disadvantages, with an emphasis on the practicality of
      implementation in malaria-endemic and non-endemic regions.

PMID- 18342280
TI  - [Consensus conference: management of differentiated thyroid cancers].

PMID- 18342281
TI  - [Guidelines for the management of differentiated thyroid cancers].

PMID- 18342282
TI  - [Annex I: surgical management of differentiated thyroid cancers].

PMID- 18342283
TI  - [Annex II: thyroglobulin determination in the follow up of differentiated cancers
      of the thyroid vesicular structure].

PMID- 18342284
TI  - [Annex III: neck ultrasound in the management of differentiated thyroid cancers].

PMID- 18342285
TI  - [Annex IV: modalities of iodine radioisotope administration and iodine 131
      scintigraphies in the management of differentiated thyroid cancers].

PMID- 18342286
TI  - [Annex V: 18-fluorodeoxyglucose positron emission tomography in the management of
      differentiated thyroid cancers].

PMID- 18342287
TI  - SLC9A6 mutations cause X-linked mental retardation, microcephaly, epilepsy, and
      ataxia, a phenotype mimicking Angelman syndrome.
AB  - Linkage analysis and DNA sequencing in a family exhibiting an X-linked mental
      retardation (XLMR) syndrome, characterized by microcephaly, epilepsy, ataxia, and
      absent speech and resembling Angelman syndrome, identified a deletion in the
      SLC9A6 gene encoding the Na(+)/H(+) exchanger NHE6. Subsequently, other mutations
      were found in a male with mental retardation (MR) who had been investigated for
      Angelman syndrome and in two XLMR families with epilepsy and ataxia, including
      the family designated as having Christianson syndrome. Therefore, mutations in
      SLC9A6 cause X-linked mental retardation. Additionally, males with findings
      suggestive of unexplained Angelman syndrome should be considered as potential
      candidates for SLC9A6 mutations.

PMID- 18342288
TI  - Effects of oxytocin-induced uterine hyperstimulation during labor on fetal oxygen
      status and fetal heart rate patterns.
AB  - OBJECTIVE: The objective of the study was to evaluate effects of oxytocin-induced
      hyperstimulation on fetal oxygen saturation and fetal heart rate patterns. STUDY
      DESIGN: Uterine activity of 56 women was evaluated retrospectively for
      hyperstimulation lasting 30 minutes using 2 definitions: group 1: 5 or more but
      less than 6 contractions in 10 minutes (n = 102, 30-minute periods); group 2: 6
      or more contractions in 10 minutes (n = 56, 30-minute periods). Fetal oxygen
      saturation and heart rate patterns during each period and the preceding 30
      minutes of less than 5 contractions in 10 minutes were compared. RESULTS:
      Hyperstimulation was associated with significant oxygen desaturation: (group 1 =
      10.68 [20%] decrease from 52.14 to 41.46; P < .001); group 2 = 15.34 [29%]
      decrease from 52.02 to 36.68: P < .001) and significantly more nonreassuring
      fetal heart rate characteristics, compared with normal uterine activity.
      CONCLUSION: Hyperstimulation is associated with negative effects on fetal status.
      The more contractions in 30 minutes, the more pronounced the effect.

PMID- 18342289
TI  - A case of recurrent hyperreactio luteinalis.
AB  - Hyperreactio luteinalis (HL) in normal pregnancy has been reported previously.
      However, only a few cases of HL recurrence have been reported. The present report
      describes HL in a normal singleton pregnancy presenting with an acute abdomen
      requiring surgical intervention. In a subsequent normal singleton pregnancy, HL
      recurred and was treated conservatively.

PMID- 18342290
TI  - The frequency and significance of intraamniotic inflammation in patients with
      cervical insufficiency.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency and clinical
      significance of intraamniotic inflammation in patients with acute cervical
      insufficiency. STUDY DESIGN: Amniocentesis was performed in 52 patients with
      acute cervical insufficiency (cervical dilation, > or =1.5 cm) and intact
      membranes and without regular uterine contractions (gestational age, 17-29
      weeks). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and
      genital mycoplasmas and assayed for matrix metalloproteinase-8. Intraamniotic
      inflammation was defined as an elevated AF matrix metalloproteinase-8
      concentration (>23 ng/mL). Nonparametric statistics and survival techniques were
      used for analysis. RESULTS: The prevalence of intraamniotic inflammation was 81%
      (42/52); the prevalence of a positive AF culture was 8% (4/52). Intraamniotic
      inflammation was present in all cases with a positive AF culture. Preterm
      delivery within 7 days occurred in 50% of cases (19/38), and delivery before 34
      weeks of gestation occurred in 84% of cases (32/38) with intraamniotic
      inflammation but without AF infection. Fifty-five percent of newborn infants
      (21/38) who were born to mothers with intraamniotic inflammation but without AF
      infection died immediately after birth (<1 day). The amniocentesis-to-delivery
      interval was shorter in patients with intraamniotic inflammation than in those
      without inflammation (P < .05). There were no differences in the interval-to
      delivery or the rate of adverse outcome between patients with intraamniotic
      inflammation and a negative culture and patients with proven AF infection.
      CONCLUSION: Intraamniotic inflammation, regardless of AF culture result, is
      present in approximately 80% of patients with acute cervical insufficiency and is
      a risk factor for impending preterm delivery and adverse outcomes.

PMID- 18342291
TI  - Gingival crevicular fluid transforming growth factor-beta1 in cyclosporine and
      tacrolimus treated renal transplant patients without gingival overgrowth.
AB  - BACKGROUND: Gingival crevicular fluid (GCF) levels of transforming growth factor
      beta(1) (TGF-beta(1)) have been previously investigated in relation to the
      pathogenesis of cyclosporine-A (CsA)-induced gingival overgrowth (GO) but no
      clinical data are available regarding the GCF levels of TGF-beta(1) in patients
      treated with tacrolimus (Tac). However, as gingival inflammation is pronounced at
      sites of GO and this consequently may lead to an elevation in TGF-beta(1) levels
      the present study aimed to evaluate gingival crevicular fluid (GCF) TGF-beta(1)
      levels in renal transplant patients using CsA or Tac without GO. METHODS: GCF TGF
      beta(1) levels were investigated in 30 renal transplant patients without GO
      medicated with either CsA (n=15) or Tac (n=15). Sixteen gingivitis patients and
      15 periodontally healthy subjects were selected as controls. Periodontal status
      was evaluated by measuring probing depth, plaque index and papilla bleeding
      index. The TGF-beta(1) levels were analysed by enzyme-linked immunosorbent assay.
      RESULTS: Both CsA and Tac groups had significantly elevated GCF TGF-beta(1) total
      amount compared to gingivitis and healthy groups (p<0.008). GCF TGF-beta(1) total
      amount of CsA and Tac groups was similar (p>0.008). Gingivitis and healthy groups
      had also similar GCF TGF-beta(1) total amount (p>0.008). CONCLUSIONS: Within the
      limits of the present data it is unlikely that TGF-beta(1) is an exclusive
      mediator of CsA- or Tac-induced GO. However, pathogenesis of GO is multifactorial
      and contribution of TGF-beta(1) to the interrelations between cytokines and
      growth factors with fibrogenic potential cannot be disregarded.

PMID- 18342292
TI  - Catastrophic associations predict level of change in anxiety sensitivity in
      response to cognitive-behavioural treatment for panic.
AB  - The aim of the present study was to elucidate one of the factors that might be
      responsible for the maintenance of panic patients' harmful beliefs about anxiety.
      Specifically, it was hypothesized that harmful beliefs about anxiety, i.e.
      anxiety sensitivity, is maintained in panic patients by automatic activation of
      idiographic catastrophic cognitions. To test this prediction, panic patients
      participated in a one-session cognitive-behavioural treatment of 4-8h to reduce
      anxiety sensitivity. The strength of automatic catastrophic cognitions in
      response to idiographic anxiety symptoms, measured with a modified semantic
      priming task, as well as the strength of the consciously accessible catastrophic
      meaning of these symptoms were assessed before treatment. In accordance with the
      hypothesis, stronger automatic catastrophic cognitions predicted a smaller
      reduction of anxiety sensitivity independently of the strength of conscious
      catastrophic cognitions. Moreover, in a first exploration, the strength of
      catastrophic associations was also shown to have an incremental predictive value
      for change in anxiety sensitivity beyond that of a number of demographic,
      clinical, treatment and assessment variables. The theoretical and clinical
      implications are discussed.

PMID- 18342293
TI  - 14-3-3 protein regulates Ask1 signaling and protects against diabetic
      cardiomyopathy.
AB  - Mammalian 14-3-3 proteins are dimeric phosphoserine-binding proteins that
      participate in signal transduction and regulate several aspects of cellular
      biochemistry. Diabetic cardiomyopathy is associated with increased oxidative
      stress and inflammation. In order to study the pathogenic changes underlying
      diabetic cardiomyopathy, we examined the role of 14-3-3 protein and apoptosis
      signal-regulating kinase 1 (Ask1) signaling by using transgenic mice with cardiac
      specific expression of a dominant-negative 14-3-3eta protein mutant (DN 14-3
      3eta) after induction of experimental diabetes. The elevation in blood glucose
      was comparable between wild type (WT) and DN 14-3-3eta mice. However, a marked
      downregulation of thioredoxin reductase was apparent in DN 14-3-3eta mice
      compared to WT mice after induction of diabetes. Significant Ask1 activation in
      DN 14-3-3eta after diabetes induction was evidenced by pronounced de
      phosphorylation at Ser-967 and intense immunofluorescence observed in left
      ventricular (LV) sections. Echocardiographic analysis revealed that cardiac
      functions were notably impaired in diabetic DN 14-3-3eta mice compared to
      diabetic WT mice. Marked increases in myocardial apoptosis, cardiac hypertrophy,
      and fibrosis were observed with a corresponding up-regulation of atrial
      natriuretic peptide and galectin-3, as well as a downregulation of
      sarcoendoplasmic reticulum Ca2+ ATPase2 expression. Furthermore, diabetic DN 14-3
      3eta mice displayed significant reductions of platelet-endothelial cell adhesion
      molecule-1 staining as well as endothelial nitric acid synthase and vascular
      endothelial growth factor expression. In conclusion, our data suggests that
      enhancement of 14-3-3 protein could provide a novel therapeutic strategy against
      hyperglycemia-induced left ventricular dysfunction and can limit the progression
      of diabetic cardiomyopathy by regulating Ask1 signaling.

PMID- 18342294
TI  - Domain mapping of a claudin-4 modulator, the C-terminal region of C-terminal
      fragment of Clostridium perfringens enterotoxin, by site-directed mutagenesis.
AB  - A C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) is a
      modulator of claudin-4. We previously found that upon deletion of the C-terminal
      16 amino acids, C-CPE lost its ability to modulate claudin-4. Tyrosine residues
      in the 16 amino acids were involved in the modulation of claudin-4. In the
      present study, we performed functional domain mapping of the 16-amino acid region
      of C-CPE by replacing individual amino acids with alanine. To evaluate the
      ability of the alanine-substituted mutants to interact with claudin-4, we carried
      out a competition analysis using claudin-4-targeting protein synthesis inhibitory
      factor. We found that Tyr306Ala, Tyr310Ala, Tyr312Ala, and Leu315Ala mutants had
      reduced binding to claudin-4 compared to C-CPE. Next, we investigated effects of
      each alanine-substituted mutant on the TJ-barrier function in Caco-2 monolayer
      cells. The TJ-disrupting activity of C-CPE was reduced by the Tyr306Ala and
      Leu315Ala substitutions. Enhancement of rat jejunal absorption was also decreased
      by each of these mutations. The double mutant Tyr306Ala/Leu315Ala lost the
      ability to interact with claudin-4, modulate TJ-barrier function, and enhance
      jejunal absorption. These data indicate that Tyr306 and Leu315 are key residues
      in the modulation of claudin-4 by C-CPE. This information should be useful for
      the development of a novel claudin modulator based on C-CPE.

PMID- 18342295
TI  - Dendritic and axonal localization of cytotoxic T-lymphocyte antigen-2 alpha
      protein in mouse brain.
AB  - Cytotoxic T-lymphocyte antigen-2 alpha (CTLA-2alpha) is a novel cysteine
      proteinase inhibitor protein originally discovered and expressed in mouse
      activated T-cells and mast cells. Expressed recombinant CTLA-2alpha is shown to
      exhibit selective inhibition of cathepsin L-like cysteine proteinases. We have
      recently reported the expression pattern of CTLA-2alpha mRNA in mouse brain by in
      situ hybridization, demonstrating that it is mainly enriched within neuronal
      populations. In this study we present the distribution profile of the protein by
      immunohistochemical analysis. Results showed that CTLA-2alpha protein is
      preferentially localized in dendritic and axonal compartments. In telencephalon,
      strong labeling was detected in dendrites in the cerebral cortices, stratum
      radiatum and stratum lacunosum moleculare and within axonal fibers of stratum
      lucidum where mossy fibers emanating from all parts of the granule cell layer of
      dentate gyrus terminate at pyramidal neurons and interneurons. In diencephalon,
      moderate staining was found in all thalamic nuclei but was strong in medial
      habenular nucleus and the hypothalamic nuclei including suprachiasmatic nucleus,
      optic chiasm, arcuate nucleus and median eminence. In mesencephalon, strong
      immunoreactivity was detected in superior colliculus, inferior colliculus and
      paramedian raphe nucleus. In the rhombencephalon, the pontine nucleus and
      transverse fibers of the pons revealed strong staining but were moderate in
      vestibular nuclei. Strong immunoreactivity was also observed in the internal
      white matter, granule cell layer and Purkinje cell layer within cerebellum. On
      Western blot analysis, a band of 14 kDa for CTLA-2alpha from protein extracts of
      the cerebrum, cerebellum, pons and medulla was detected. The distribution pattern
      and functional considerations of CTLA-2alpha in the brain are discussed.

PMID- 18342296
TI  - Microinjection of the vehicle dimethyl sulfoxide (DMSO) into the periaqueductal
      gray modulates morphine antinociception.
AB  - Dimethyl sulfoxide (DMSO) is commonly used as a solvent for water-insoluble
      drugs. Given that DMSO has varying cellular and behavioral effects ranging from
      increased membrane permeability to toxicity, microinjection of DMSO as a vehicle
      could confound the effects of other drugs. For example, DMSO is often used as a
      vehicle for studies examining the neurochemical mechanisms underlying morphine
      antinociception. Given that the ventrolateral periaqueductal gray (vlPAG) plays a
      major role in morphine antinociception and tolerance, the effects of DMSO on
      morphine antinociception mediated by the vlPAG needs to be evaluated. The present
      experiment tested whether co-administration of DMSO (0, 0.2, 2, or 20%) would
      alter the antinociceptive effect of microinjecting morphine into the vlPAG. DMSO
      had no effect on nociception when microinjected into the vlPAG alone, but 2% DMSO
      enhanced morphine potency when co-administered with morphine. In contrast, twice
      daily microinjections of DMSO (5 or 20%) for two days reduced the potency of
      subsequent microinjections of morphine into the vlPAG--an effect that persisted
      for at least one week. A similar rightward shift in the morphine dose-response
      curve was caused by morphine tolerance. Co-administration of morphine and DMSO
      during the pretreatment did not cause a greater shift in the morphine dose
      response curve compared to morphine pretreated alone. In conclusion, DMSO can
      alter morphine antinociception following both acute (enhancement) and chronic
      (inhibition) administration depending on the concentration. These data reinforce
      the need to be cautious when using DMSO as a vehicle for drug administration.

PMID- 18342297
TI  - Repetitive hyperbaric oxygen exposures enhance sensitivity to convulsion by
      upregulation of eNOS and nNOS.
AB  - BACKGROUND: Repetitive hyperbaric oxygen (HBO) exposures as preconditioning
      methods produce ischemic tolerance, but may increase the risk of convulsions in
      patients. The purpose of this study was to investigate the mechanisms in
      increased sensitivity to convulsions and the role of nitric oxide (NO) and its
      synthases after repetitive HBO exposures. METHODS: Mice were randomly assigned
      into three groups: HBO group, hyperbaric air (HBA) group and normobaric air (NBA)
      group. Mice in HBO or HBA group were exposed to hyperbaric oxygen or hyperbaric
      air respectively for 60 min twice daily for 3 consecutive days (2.5 atmosphere
      absolute [ATA]). 24 h after the last exposure, mice were exposed to HBO (100% O2,
      6 ATA). The latency of convulsions was recorded. In addition, the levels of NO,
      NADPH-diaphorase, mRNA and protein expressions of NOS isoforms in hypothalamus
      and hippocampus were determined. RESULTS: Latency to seizures was significantly
      shortened in mice after six HBO pre-exposures. The level of NO in hypothalamus in
      HBO group was increased. The number of NADPH-d positive cells and the levels of
      protein and mRNA of eNOS and nNOS in hypothalamus and hippocampus were increased.
      CONCLUSION: After repeated HBO exposures, elevated NO may enhance the sensitivity
      to convulsions and this may lead to seizures during the subsequent oxygen
      exposures. Prevention of seizures is needed when HBO is used as preconditioning
      method.

PMID- 18342298
TI  - Chemical analysis of a new fucoglucan isolated from an edible mushroom,
      Termitomyces robustus.
AB  - A water-soluble fucoglucan, isolated from alkali-treated edible mushroom,
      Termitomyces robustus, consists of L-fucose and D-glucose in a molar proportion
      of 1:4. Structural investigation of the polysaccharide was carried out by using
      total hydrolysis, methylation analysis, and periodate oxidation followed by GLC
      MS, and the final structure was determined using NMR experiments (1H, 13C, DQF
      COSY, TOCSY, NOESY, ROESY, HMQC, and HMBC). On the basis of the above experiments
      it is concluded that the following repeating unit is present in the
      polysaccharide: [Formula: see text].

PMID- 18342299
TI  - Reference directions and reference objects in spatial memory of a briefly viewed
      layout.
AB  - Two experiments investigated participants' spatial memory of a briefly viewed
      layout. Participants saw an array of five objects on a table and, after a short
      delay, indicated whether the target object indicated by the experimenter had been
      moved. Experiment 1 showed that change detection was more accurate when non
      target objects were stationary than when non-target objects were moved. This
      context effect was observed when participants were tested both at the original
      learning perspective and at a novel perspective. In Experiment 2, the arrays of
      five objects were presented on a rectangular table and two of the non-target
      objects were aligned with the longer axis of the table. Change detection was more
      accurate when the target object was presented with the two objects that were
      aligned with the longer axis of the table during learning than when the target
      object was presented with the two objects that were not aligned with the longer
      axis of the table during learning. These results indicated that the spatial
      memory of a briefly viewed layout has interobject spatial relations represented
      and utilizes an allocentric reference direction.

PMID- 18342300
TI  - Age-associated increase in aneuploidy and changes in gene expression in mouse
      eggs.
AB  - An increase in the incidence of aneuploidy is well documented with increasing
      maternal age, in particular in human females. Remarkably, little is known
      regarding the underlying molecular basis for the age-associated increase in
      aneuploidy, which is a major source of decreased fertility in humans. Using mouse
      as a model system we find that eggs obtained from old mice (60-70 weeks of age)
      display a 6-fold increase in the incidence of hyperploidy as assessed by
      chromosome spreads. Expression profiling of transcripts in oocytes and eggs
      obtained from young and old mice reveals that approximately 5% of the transcripts
      are differentially expressed in oocytes obtained from old females when compared
      to oocytes obtained from young females (6-12 weeks of age) and that this fraction
      increases to approximately 33% in eggs. The latter finding indicates that the
      normal pattern of degradation of maternal mRNAs that occurs during oocyte
      maturation is dramatically altered in eggs obtained from old mice and could
      therefore be a contributing source to the decline in fertility. Analysis of the
      differentially expressed transcripts also indicated that the strength of the
      spindle assembly checkpoint is weakened and that higher errors of microtubule
      kinetochore interactions constitute part of molecular basis for the age
      associated increase in aneuploidy in females. Last, BRCA1 expression is reduced
      in oocytes obtained from old females and RNAi-mediated reduction of BRCA1 in
      oocytes obtained from young females results in perturbing spindle formation and
      chromosome congression following maturation.

PMID- 18342302
TI  - Regulation of cytosolic and mitochondrial ATP levels in mouse eggs and zygotes.
AB  - Fertilization activates development by stimulating a plethora of ATP consuming
      processes that must be provided for by an up-regulation of energy production in
      the zygote. Sperm-triggered Ca(2+) oscillations are known to be responsible for
      the stimulation of both ATP consumption and ATP supply but the mechanism of up
      regulation of energy production at fertilization is still unclear. By measuring
      [Ca(2+)] and [ATP] in the mitochondria of fertilized mouse eggs we demonstrate
      that sperm entry triggers Ca(2+) oscillations in the cytosol that are transduced
      into mitochondrial Ca(2+) oscillations pacing mitochondrial ATP production. This
      results, during fertilization, in an increase in both [ATP](mito) and
      [ATP](cyto). We also observe the stimulation of ATP consumption accompanying
      fertilization by monitoring [Ca(2+)](cyto) and [ATP](cyto) during fertilization
      of starved eggs. Our observations reveal that lactate, in contrast to pyruvate,
      does not fuel mitochondrial ATP production in the zygote. Therefore lactate
      derived pyruvate is somehow diverted from mitochondrial oxidation and may be
      channeled to other metabolic routes. Together with our earlier findings, this
      study confirms the essential role for exogenous pyruvate in the up-regulation of
      ATP production at the onset of development, and suggests that lactate, which does
      not fuel energetic metabolism may instead regulate the intracellular redox
      potential.

PMID- 18342301
TI  - Misexpression of MIA disrupts lung morphogenesis and causes neonatal death.
AB  - Microarray experiments designed to identify genes differentially expressed in the
      E11.5 lung and trachea showed that melanoma inhibitory activity (Mia1) was
      expressed only in the lung. Mia1 was abundantly expressed during early lung
      development, but was virtually absent by the end of gestation. Distal embryonic
      lung epithelium showed high levels of Mia1 expression, which was suppressed by
      treatment with either retinoic acid or the FGF signaling antagonist SU5402. Late
      gestation fetuses in which lung epithelial hyperplasia was induced by
      misexpression of FGF7 or FGF10 showed continued expression of Mia1 in areas of
      aberrant morphogenesis. Mia1 expression was also significantly increased in
      urethane-induced lung adenomas. Treatment of E18.5 lung explants with exogenous
      MIA caused significant reductions in the expression of the lung differentiation
      markers Sftpa, Sftpb, Sftpc, and Abca3. Bitransgenic mice expressing MIA under
      the control of the SFTPC promoter after E16.5, the age when Mia1 is normally
      silenced, died from respiratory failure at birth with morphologically immature
      lungs associated with reduced levels of saturated phosphatidylcholine and mature
      SP-B. Microarray analysis showed significant reductions in the expression of
      Sftpa, Sftpb, Abca3, Aqp5, Lzp-s, Scd2, and Aytl2 in lungs misexpressing MIA.
      These results suggest that the silencing of Mia1 that occurs in late gestation
      may be required for maturation of the surfactant system.

PMID- 18342303
TI  - Complex cell rearrangements during intersegmental vessel sprouting and vessel
      fusion in the zebrafish embryo.
AB  - The formation of intersegmental blood vessels (ISVs) in the zebrafish embryo
      serves as a paradigm to study angiogenesis in vivo. ISV formation is thought to
      occur in discrete steps. First, endothelial cells of the dorsal aorta migrate out
      and align along the dorsoventral axis. The dorsal-most cell, also called tip
      cell, then joins with its anterior and posterior neighbours, thus establishing a
      simple vascular network. The vascular lumen is then established via formation of
      vacuoles, which eventually fuse with those of adjacent endothelial cells to
      generate a seamless tube with an intracellular lumen. To investigate the cellular
      architecture and the development of ISVs in detail, we have analysed the
      arrangement of endothelial cell junctions and have performed single cell live
      imaging. In contrast to previous reports, we find that endothelial cells are not
      arranged in a linear head-to-tail configuration but overlap extensively and form
      a multicellular tube, which contains an extracellular lumen. Our studies
      demonstrate that a number of cellular behaviours, such as cell divisions, cell
      rearrangements and dynamic alterations in cell-cell contacts, have to be
      considered when studying the morphological and molecular processes involved in
      ISV and endothelial lumen formation in vivo.

PMID- 18342304
TI  - Xenopus tropicalis allurin: expression, purification, and characterization of a
      sperm chemoattractant that exhibits cross-species activity.
AB  - Previously we reported the identification of the first vertebrate sperm
      chemoattractant, allurin, in the frog Xenopus laevis (Xl) and demonstrated that
      it was a member of the CRISP family of proteins. Here we report identification,
      purification, and characterization of Xenopus tropicalis (Xt) allurin, a
      homologous protein in X. tropicalis. "Egg water" as well as purified allurin from
      both species exhibit efficient cross-species sperm chemoattractant activity.
      Western blots show that Xt egg water contains a single anti-allurin cross
      reactive protein whose molecular weight (20,497 Da by MALDI MS) agrees well with
      the molecular weight of the hypothetical gene product for a newly recognized
      "Crisp A" gene in the X. tropicalis genome. A recombinant form of the protein,
      expressed in 3T3 cells, exhibits chemoattraction for both Xt and Xl sperm and
      cross reacts with anti-allurin antibodies. Examination of Crisp protein
      expression in the Xt oviduct using RT-PCR showed that of five documented Xt Crisp
      genes (Crisps 2, 3, LD1, LD2 and A) only Crisp A was expressed. In contrast,
      Crisp 2, Crisp 3, Crisp LD1, and Crisp LD2, but not Crisp A, were all found to be
      expressed in the Xt testes while subsets of Crisp proteins where expressed in the
      Xt ovary. These data suggest that Crisp proteins in amphibians may play multiple
      roles in sperm production, maturation and guidance just as they are thought to in
      mammals indicating that Crisp protein involvement in reproduction may not be
      limited to mammals.

PMID- 18342305
TI  - Gene transfer of dimethylarginine dimethylaminohydrolase-2 improves the
      impairments of DDAH/ADMA/NOS/NO pathway in endothelial cells induced by
      lysophosphatidylcholine.
AB  - Dimethylarginine dimethylaminohydrolase (DDAH) is a key enzyme responsible for
      the metabolism of nitric oxide (NO) synthase (NOS) inhibitor asymmetric
      dimethylarginine (ADMA), and DDAH2 is the predominant isoform in vascular
      endothelium. Lysophosphatidylcholine (LPC) and ADMA are implicated in endothelial
      dysfunction of atherosclerosis. This study was to examine changes in
      DDAH/ADMA/NOS/NO pathway in endothelial cells after exposure to LPC and
      investigate whether DDAH2 gene transfer could reverse LPC-induced changes. Human
      endothelial cell line ECV304 cells were transfected with recombinant pcDNA3.1
      hDDAH2 plasmid and incubated with 3 micromol/L LPC for 48 h. Cells were harvested
      for assays of DDAH transcription, DDAH and NOS activities. The culture medium was
      collected for measurements of ADMA and nitrite/nitrate concentrations. LPC
      treatment suppressed DDAH2 transcription and DDAH activity in parallel with
      increased ADMA concentration, inhibited NOS activity and decreased NO metabolites
      content. DDAH2 gene transfer not only prevented the suppression of DDAH activity
      and the elevation of endogenous ADMA, but also attenuated the inhibition of NOS
      activity and the reduction of NO level induced by LPC in endothelial cells. These
      results suggest that LPC induces impairments of DDAH/ADMA/NOS/NO pathway, and
      DDAH2 gene transfer could improve the LPC-elicited impairments in endothelial
      cells.

PMID- 18342306
TI  - In vivo neurochemical effects of the NR2B selective NMDA receptor antagonist CR
      3394 in 6-hydroxydopamine lesioned rats.
AB  - Microdialysis in intact and denervated striatum of unilaterally 6-hydroxydopamine
      (6-OHDA) lesioned rats was used to investigate whether CR 3394, N-[2-(3,5
      dimethyl-1-adamantyl)ethyl]acetamidine, an adamantane derivative with
      preferential selectivity for the NR2B subunit of the NMDA receptor, has dopamine
      releasing properties in vivo. We also investigated whether this NMDA antagonist
      can potentiate the effects of L-Dopa on extracellular dopamine in these animals.
      After systemic injection, there was no significant effect of CR 3394 on
      extracellular dopamine, at all doses studied (1, 5 and 20 mg/kg i.p.), in either
      intact or in denervated striatum. On the other hand, striatal perfusion with 100
      microM of the compound elicited release of dopamine in intact, but not in
      denervated striatum. In denervated striatum of the 6-OHDA-lesioned rats, CR 3394
      (5 mg/kg) significantly enhanced the dopamine release induced by L-Dopa
      administration (25 mg/kg i.p.) in combination with benserazide (10 mg/kg i.p.).
      In particular, the onset of action of L-Dopa was potentiated. However, when
      combined with a subthreshold dose of L-Dopa (5 mg/kg), the effects of CR 3394
      were lost. We conclude that CR 3394, like other NR2B receptor antagonists, has
      dopamine releasing properties in vivo. It enhances the effects of suprathreshold
      doses of L-Dopa in the denervated striatum, but not of low doses of L-Dopa.
      Therefore, future studies are necessary to establish the potential of selective
      NR2B receptor antagonists as L-Dopa-sparing agents.

PMID- 18342307
TI  - The beta-lactam antibiotic ceftriaxone inhibits physical dependence and
      abstinence-induced withdrawal from cocaine, amphetamine, methamphetamine, and
      clorazepate in planarians.
AB  - Ceftriaxone (a beta-lactam antibiotic) has recently been identified as having the
      rare ability to increase the expression and functional activity of the glutamate
      transporter subtype 1 (GLT-1) in rat spinal cord cultures. GLT-1 has been
      implicated in diverse neurological disorders and in opioid dependence and
      withdrawal. It has been speculated that it might also be involved in the physical
      dependence and withdrawal of other abused drugs, but demonstration of this
      property can be difficult in mammalian models. Here, we demonstrate for the first
      time using a planarian model that ceftriaxone attenuates both the development of
      physical dependence and abstinence-induced withdrawal from cocaine, amphetamine,
      methamphetamine, and a benzodiazepine (clorazepate) in a concentration-related
      manner. These results suggest that physical dependence and withdrawal from
      several drugs involve a common - beta-lactam-sensitive - mechanism in planarians.
      If these findings can be shown to extend to mammals, beta-lactam antibiotics
      might represent a novel pharmacotherapy or adjunct approach for treating drug
      abuse or serve as a template for drug discovery efforts aimed at treating drug
      abuse, recovery from drug abuse, or ameliorating the withdrawal from chronic use
      of therapeutic medications.

PMID- 18342308
TI  - Focus on molecules: connexin 43--mind the gap.

PMID- 18342309
TI  - Pallidal neuronal discharge in Huntington's disease: support for selective loss
      of striatal cells originating the indirect pathway.
AB  - Chorea is the predominant motor manifestation in the early symptomatic phase of
      adult onset Huntington's disease (HD). Pathologically, this stage is marked by
      differential loss of striatal neurons contributing to the indirect pathway. This
      pattern of neuronal loss predicts decreased neuronal firing rates in GPi and
      increased firing rates in GPe, the opposite of the changes in firing rate known
      to occur in Parkinson's disease (PD). We present single-unit discharge
      characteristics (33 neurons) observed in an awake patient with HD (41 CAG
      repeats) undergoing microelectrode guided surgery for pallidal deep brain
      stimulation. Pallidal single-unit activity at "rest" and during voluntary
      movement was discriminated off line by principal component analysis and evaluated
      with respect to discharge rate, bursting, and oscillatory activity in the 0-200
      Hz range. 24 GPi and 9 GPe units were studied, and compared with 132 GPi and 50
      GPe units from 14 patients with PD. The mean (+/-SEM) spontaneous discharge rate
      for HD was 58+/-4 for GPi and 73+/-5 for GPe. This contrasted with discharge
      rates in PD of 95+/-2 for GPi and 57+/-3 for GPe. HD GPi units showed more
      bursting than PD GPi units but much less oscillatory activity in the 2-35 Hz
      frequency range at rest. These findings are consistent with selective early loss
      of striatal cells originating the indirect pathway.

PMID- 18342310
TI  - Caloric restriction and age affect synaptic proteins in hippocampal CA3 and
      spatial learning ability.
AB  - Caloric restriction (CR) is a daily reduction of total caloric intake without a
      decrease in micronutrients or disproportionate reduction of any one dietary
      component. CR can increase lifespan reliably in a wide range of species and
      appears to counteract some aspects of the aging process throughout the body. The
      effects on the brain are less clear, but moderate CR seems to attenuate age
      related cognitive decline. Thus, we determined the effects of age and CR on key
      synaptic proteins in the CA3 region of the hippocampus and whether these changes
      were correlated with differences in behavior on a hippocampal-dependent learning
      and memory task. We observed an overall, age-related decline in the NR1, N2A and
      N2B subunits of the N-methyl-d-aspartate (NMDA)-type and the GluR1 and GluR2
      subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)
      type ionotropic glutamate receptors. Interestingly, we found that CR initially
      lowers the glutamate receptor subunit levels as compared to young AL animals, and
      then stabilizes the levels across lifespan. Synaptophysin, a presynaptic vesicle
      protein, showed a similar pattern. We also found that both CR and ad libitum (AL)
      fed animals exhibited age-related cognitive decline on the Morris water maze
      task. However, AL animals declined between young and middle age, and between
      middle age and old, whereas CR rats only declined between young and middle age.
      Thus, the decrease in key synaptic proteins in CA3 and cognitive decline
      occurring across lifespan are stabilized by CR. This age-related decrease and CR
      induced stabilization are likely to affect CA3 synaptic plasticity and, as a
      result, hippocampal function.

PMID- 18342311
TI  - Echinococcus granulosus: variability of the host-protective EG95 vaccine antigen
      in G6 and G7 genotypic variants.
AB  - Cystic hydatid disease in humans is caused by the zoonotic parasite Echinococcus
      granulosus. As an aid to control transmission of the parasite, a vaccine has been
      produced for prevention of infection in the parasite's natural animal
      intermediate hosts. The vaccine utilizes the recombinant oncosphere protein,
      EG95. An investigation into the genetic variability of EG95 was undertaken in
      this study to assess potential antigenic variability in E. granulosus with
      respect to this host-protective protein. Gene-specific PCR conditions were first
      established to preferentially amplify the EG95 vaccine-encoding gene (designated
      eg95-1) from the E. granulosus genome that also contains several other EG95
      related genes. The optimized PCR conditions were used to amplify eg95-1 from
      several parasite isolates in order to determine the protein-coding sequence of
      the gene. An identical eg95-1 gene was amplified from parasites showing a G1 or
      G2 genotype of E. granulosus. However, from isolates having a G6 or G7 genotype,
      a gene was amplified which had substantial nucleotide substitutions (encoding
      amino acid substitutions) compared with the eg95 gene family members. The amino
      acid substitutions of EG95 in the G6/G7 genotypes may affect the
      antigenicity/efficacy of the EG95 recombinant antigen against parasites of these
      genotypes. These findings indicate that characterization of eg95 gene family
      members in other strains/isolates of E. granulosus may provide valuable
      information about the potential for the EG95 hydatid vaccine to be effective
      against E. granulosus strains other than the G1 genotype.

PMID- 18342312
TI  - Appearances and chronological changes of mummichog Fundulus heteroclitus FSH
      cells and LH cells during ontogeny, sexual differentiation, and gonadal
      development.
AB  - To examine relationships between gonadal stages and the initial appearance and
      subsequent development of gonadotrophs, hatched larvae of the mummichog Fundulus
      heteroclitus were reared until first maturity under suitable conditions for
      maturation (20 degrees C-16L). Evident FSH cells generally appeared 1-2 weeks
      after hatching (wah), around or slightly before the morphological sex
      differentiation which occurred at 2 wah. During this period, 3beta-hydroxysteroid
      dehydrogenase positive cells also appeared in the gonads. While FSH cells existed
      throughout the early phases of gonadal development such as cortical alveoli
      formation and basic spermatogenesis, LH cells appeared later (6-12 wah), after
      the commencement of the early gonadal development. Both FSH cells and LH cells
      were abundant at 36 wah when the fish had attained full maturity. These results
      indicate the possibility that FSH is responsible for gonadal differentiation by
      inducing steroidogenesis in the gonads, implying the importance of FSH on the
      early phases of gonadal development. These results also suggest cooperation of
      FSH and LH in later phases of gonadal development such as yolk globule
      accumulation and active spermatogenesis. The mode of changes in the abundances of
      the gonadotrophs according to the gonadal development was somewhat different from
      previously observed changes during the annual reproductive cycle in adult
      mummichog. Possible complementary roles of the two GTHs in vitellogenesis and
      spermatogenesis may be involved in the difference by providing flexibility to the
      controlling mechanism.

PMID- 18342313
TI  - Isolation and expression of the retinoid X receptor from last instar nymphs and
      adult females of the soft tick Ornithodoros moubata (Acari: Argasidae).
AB  - Retinoid X receptors (RXR) exist broadly from invertebrates to vertebrates, and
      play essential roles in physiological processes of these organisms. In
      arthropods, RXRs form a complex with the ecdysteroid receptor (EcR) and
      ecdysteroids to mediate the regulation of ecdysis and reproduction. Compared to
      EcR, RXR and its homologue ultraspiracle (USP) are much less well understood.
      Therefore, we identified RXR of the soft tick Ornithodoros moubata (OmRXR) and
      used real-time PCR to examine the expression of OmRXR. This is the first report
      of RXR from a soft tick. OmRXR showed higher homology to hard tick, crustacean
      and vertebrate RXRs than insect RXRs and USPs. OmRXR expression was observed
      during molting in the last instar nymphs coinciding with EcR expression and
      increases in ecdysteroid titers. Tick vitellogenesis normally occurs soon after
      engorgement and OmRXR expression coinciding with EcR expression and ecdysteroid
      titers in engorged females occurred before vitellogenin (Vg) synthesis and egg
      maturation. The ecdysteroid/EcR/RXR complex appears to be important in the
      regulation of molting and vitellogenesis of soft ticks.

PMID- 18342314
TI  - Vitellogenin, steroid plasma levels and spawning performance of cultured female
      Senegalese sole (Solea senegalensis).
AB  - The Senegalese sole (Solea senegalensis) is a high value market flatfish, which
      aquaculture is compromised by severe reproductive problems; these are mostly
      found in soles hatched and raised in captivity (F1 generation). To gain knowledge
      on the reproductive dysfunctions observed in cultured (F1) Senegalese sole, this
      work aimed at developing a specific vitellogenin (VTG) ELISA, for the measurement
      of plasma VTG levels in this species. Profiles of VTG were correlated with those
      of sexual steroids and spawning performance of an F1 broodstock, during three
      consecutive years. The Senegalese sole VTG (ssVTG) was purified by precipitation
      with MgCl(2)-EDTA and anion-exchange chromatography and showed a molecular mass
      of 172 kDa, by SDS-PAGE. Specific antibodies were obtained and used to develop a
      competitive ELISA, which had a sensitivity of 3.6 ng ml(-1), and inter- and intra
      assay coefficients of variation of 9.5% (n=29) and 6.7% (n=12), respectively.
      Annual profiles of plasma VTG showed a major peak at pre-spawning, and a second
      minor rise around autumn, which mirrored plasma profiles of both estradiol (E(2))
      and testosterone (T) levels. Spontaneous spawning occurred every year in the
      spring season, but no fertilized eggs were obtained. In conclusion, this study
      described, for the first time, the purification and development of a sensitive
      and specific ELISA for Senegalese sole VTG. The endocrine and spawning data
      suggested that F1 female broodstock showed normal VTG and steroid releasing
      profiles in captivity with occurrence of spontaneous spawning, but no
      fertilization of the eggs was recorded.

PMID- 18342315
TI  - Doctoral education in the context of international development strategies.

PMID- 18342316
TI  - Myxozoan parasitism in waterfowl.
AB  - Myxozoans are spore-forming, metazoan parasites common in cold-blooded aquatic
      vertebrates, especially fishes, with alternate life cycle stages developing in
      invertebrates. We report nine cases of infection in free-flying native and
      captive exotic ducks (Anseriformes: Anatidae) from locations across the United
      States and describe the first myxozoan in birds, Myxidium anatidum n. sp. We
      found developmental stages and mature spores in the bile ducts of a Pekin duck
      (domesticated Anas platyrhynchos). Spores are lens-shaped in sutural view,
      slightly sigmoidal in valvular view, with two polar capsules, and each valve cell
      has 14-16 longitudinal surface ridges. Spore dimensions are 23.1 microm x 10.8
      microm x 11.2 microm. Phylogenetic analysis of the ssrRNA gene revealed closest
      affinity with Myxidium species described from chelonids (tortoises). Our novel
      finding broadens the definition of the Myxozoa to include birds as hosts and has
      implications for understanding myxozoan evolution, and mechanisms of geographical
      and host range extension. The number of infection records indicates this is not
      an incidental occurrence, and the detection of such widely dispersed cases
      suggests more myxozoans in birds will be encountered with increased surveillance
      of these hosts for pathogens.

PMID- 18342317
TI  - Matrix metalloproteinase-3 (MMP3) and MMP9 genes and risk of myocardial
      infarction, ischemic stroke, and hemorrhagic stroke.
AB  - OBJECTIVE: We assessed the association of genetic variation in MMP3 and MMP9 with
      risk of myocardial infarction and stroke. METHODS: A case-control study was
      conducted among members of Group Health (GH), a large-integrated health care
      delivery system. Case subjects with incident non-fatal myocardial infarction
      (n=854), ischemic stroke (n=367), and hemorrhagic stroke (n=66) were identified
      and validated. A matched control group was selected from among GH members without
      myocardial infarction or stroke (n=2696). Haplotype-tagging sets of single
      nucleotide polymorphisms (SNPs) in MMP3 and MMP9 were genotyped. RESULTS: MMP3
      haplotype 2 was associated with reduced risk of myocardial infarction (adjusted
      odds ratio (OR) per copy=0.80, 95% confidence interval 0.66, 0.98) and increased
      risk of hemorrhagic stroke (OR=1.69, 95% confidence interval 1.05, 2.75). Results
      for MMP3 haplotype 2 and ischemic stroke resembled those for myocardial
      infarction but did not achieve statistical significance (OR=0.85, 95% confidence
      interval 0.64, 1.12). No individual SNP identified MMP3 haplotype 2, and none of
      the individual MMP3 SNPs were associated with myocardial infarction or stroke.
      MMP9 haplotypes or SNPs were not associated with myocardial infarction or stroke.
      CONCLUSIONS: MMP3 haplotype may predict both cardiac events and stroke.

PMID- 18342318
TI  - Bacterial signatures in atherosclerotic lesions represent human commensals and
      pathogens.
AB  - BACKGROUND: Various studies have suggested the involvement of infectious agents
      in chronic inflammatory diseases, including atherosclerosis. By using a novel
      subtraction broad-range PCR approach, we defined bacterial DNA signatures in
      surgically removed sterile abdominal aorta samples of patients with aortic
      atherosclerosis. METHODS: Partial bacterial 16S rDNA nucleotide sequences were
      determined using broad-range PCR from aortic samples of 20 patients, and from
      appropriate methodological controls. In all, 160 sequences from 16 clone
      libraries were studied. RESULTS: After subtraction analysis 16 clinically
      relevant bacterial sequence-types were identified among the patient samples,
      whereas 29 were discarded as potential methodological contaminants. On average
      2.2+/-1.2 different bacterial sequence-types were present in the nine true PCR
      positive atheroma samples. CONCLUSIONS: Many studies have reported the presence
      of a variety of bacterial sequences from atherosclerotic lesions. However, the
      results obtained with these PCR technologies may have been skewed by
      methodological contaminants. After our subtraction approach, 63% of the remaining
      sequence-types from sites of aortic atherosclerosis were related to those of
      known human pathogens. This may imply that advanced atherosclerotic plaques
      accumulate bacterial DNA.

PMID- 18342319
TI  - Optimality in forward dynamics simulations.
AB  - This paper discusses a methodology and an algorithm for the analysis of dynamics
      of bio-mechanical systems, and in particular of optimal movement patterns between
      initial and target configurations. The basic formulation utilizes a finite
      element time discretization and establishes a large set of equations in
      displacements and forces. These are solved simultaneously for the whole time
      interval considered. The algorithm allows different optimization criteria for the
      movement, based on either the smoothness of the movement or the minimization of
      needed controls or control rates. It is primarily aimed at musculoskeletal
      simulations with either the joint resultant moments or the redundant muscular
      tensions as unknowns. Kinetic and kinematic constraints can be introduced for the
      obtained movement. Examples show that the obtained results are strongly dependent
      on the optimality criterion used. Systematic usage of the algorithm can improve
      knowledge about optimal motion planning.

PMID- 18342320
TI  - Quantitative associations between osteocyte density and biomechanics, microcrack
      and microstructure in OVX rats vertebral trabeculae.
AB  - Osteocytes actively regulate bone modeling and remodeling, direct skeletal
      mineralization, and regulate calcium/phosphate homeostasis and extracellular
      matrix metabolism; yet the specific role of osteocytes in maintaining bone
      structural integrity and strength is unknown. Studies have shown that the density
      of osteocytes decreases with age and estrogen deficiency, as seen in
      postmenopausal women. Here, we examined the relationships between osteocyte
      density and the related variables, including biomechanics, bone mineral density,
      microcrack and microstructure of vertebral trabeculae, in ovariectomized rats. We
      found that osteocyte density correlated with some of the parameters that
      determine the biomechanical quality of bone. Our findings suggest that osteocytes
      could play a crucial role in maintaining the mechanical quality of bone, and
      osteocyte density could be considered as an alternative index in assessing bone
      quality.

PMID- 18342321
TI  - An automated method for the simultaneous determination of pravastatin, 3-hydroxy
      isomeric metabolite, pravalactone and fenofibric acid in human plasma by
      sensitive liquid chromatography combined with diode array and tandem mass
      spectrometry detection.
AB  - In this study, a sensitive and selective method based on liquid chromatography
      combined with diode array and tandem mass spectrometry detection (LC-DAD-MS/MS)
      was developed for the simultaneous quantitative determination of fenofibric acid,
      pravastatin and its main metabolites in human plasma. In this method, an
      automated solid-phase extraction (SPE) on disposable extraction cartridges (DECs)
      is used to isolate the compounds from the biological matrix and to prepare a
      cleaner sample before injection and analysis in the LC-DAD-MS/MS system. On-line
      LC-DAD-MS/MS system using an atmospheric pressure ionization (TurboIonSpray) was
      then developed for the simultaneous determination of pravastatin, 3-hydroxy
      isomeric metabolite (3-OH metab), pravalactone and fenofibric acid. The
      separation is obtained on an endcapped dodecyl silica based stationary phase
      using a mobile phase consisting of a mixture of acetonitrile, methanol and 5mM
      ammonium acetate solution (30:30:40, v/v/v). Sulindac and triamcinolone were used
      as internal standards (ISs). The detection of the fenofibric acid and sulindac
      was achieved by means of a DAD system. The MS/MS ion transitions monitored were
      m/z 442.2-->269.1, 442.2-->269.1, 424.3-->183.0 and 435.2-->397.2 for
      pravastatin, 3-OH metab, pravalactone and triamcinolone, respectively. The method
      was validated regarding stability, selectivity, extraction efficiency, response
      function, trueness, precision lower limit of quantitation and matrix effect. The
      limits of quantitation (LOQs) were around 0.50 ng/ml for pravastatin, 0.25 ng/ml
      for 3-OH metab, 0.05 ng/ml for pravalactone and 0.25 microg/ml for fenofibric
      acid.

PMID- 18342322
TI  - p-tert-Butylcalix[8]arene-bonded silica monoliths for liquid chromatography.
AB  - Monolithic silica columns have inspired considerable research interests in the
      separation science because of their unique properties in permeability, mass
      transfer, efficiency and throughput. In this paper, a chemically p-tert
      butylcalix[8]arene-bonded silica monolith was prepared as the promising candidate
      for versatile LC separations. Micrometer-sized macropores and nanometer-sized
      mesopores in this derivatized silica monolith reduce the diffusion path length
      and provide both low backpressure and high column efficiencies, leading to high
      speed and high-throughput separations. Since p-tert-butylcalix[8]arene possesses
      a pi-donors cavity composed of benzene rings while polycyclic aromatic
      hydrocarbons, anthraquinones, phenol regio isomers and fullerenes are pi-systems
      with appreciable electron affinity, they may have a chance to get involved in
      forming host-guest inclusion complexes through non-covalent interactions, e.g.
      hydrophobic and pi-pi interactions. Compared with RP-18e, the prepared calixarene
      bonded monolith exhibited better selectivity to molecules which contains more pi
      electrons and more condensed cyclic moieties. The column efficiency was about
      22,000 plates/m. The calixarene-bonded monolith also showed its good performances
      in separation of fullerenes and dihydropyridines, indicating a promising approach
      for purification of fullerenes with high purity from the carbon soot.

PMID- 18342323
TI  - Application of surface complexation modeling to the reactivity of iron(II) with
      nitroaromatic and oxime carbamate contaminants in aqueous TiO2 suspensions.
AB  - This study reports on the application of surface complexation modeling to
      interpret observed kinetic trends for Fe(II) redox reactions with model
      nitroaromatic (4-chloronitrobenzene) and oxime carbamate (oxamyl) contaminants in
      aqueous TiO(2(s)) suspensions. Pseudo-first-order rate constants for reduction of
      the two probe contaminants (k(red), s(-1)) vary by several orders of magnitude
      with changing conditions (100-500 microM Fe(II), 0-15 g L(-1) TiO(2(s)), pH 2-9),
      but the relationship between reaction rates and Fe(II) speciation differs
      considerably for the two contaminants. For oxamyl, k(red) measurements are most
      strongly correlated with the volumetric total adsorbed Fe(II) concentration
      (moles Fe(II) adsorbed per liter of TiO(2(s)) suspension), whereas k(red)
      measurements for 4-chloronitrobenzene are proportional to the concentration of
      the hydrolyzed Fe(II) surface complex (equivalent TiOFe(II)OH(0)). The differing
      trends demonstrate that Fe(II) redox reactivity at the aqueous/TiO(2(s))
      interface is influenced, in part, by specific molecular interactions with the
      target oxidant. Results are also geochemically relevant in that they demonstrate
      unambiguously that mononuclear Fe(II)-metal (hydr)oxide surface complexes are
      sufficiently reactive species to reduce nitroaromatic contaminants, an issue that
      remained open following earlier studies in Fe(III) (hydr)oxide suspensions
      because structural Fe(II) species are simultaneously present in such systems
      because of interfacial Fe(II)-to-Fe(III) electron transfer processes that occur
      on Fe(II) adsorption.

PMID- 18342324
TI  - Solvent effect on the film formation and the stability of the surface properties
      of poly(methyl methacrylate) end-capped with fluorinated units.
AB  - The surface structure and stability (the resistance to surface reconstruction) of
      end-capped poly(methyl methacrylate) films were greatly affected by the solvents
      used for film preparation. Films of end-capped PMMA with about four 2
      perfluorooctylethyl methacrylate units cast with benzotrifluoride solution
      exhibited excellent stability and resistance to polar environments compared with
      those cast with cyclohexanone and toluene solutions. The observed difference in
      stability between these fluorinated surfaces is attributed to their surface
      microstructures formed during the film formation processes, which are closely
      related to the associative behavior of the end-capped PMMA in the solution. A
      relatively perfect close-packed and well-ordered structure of the perfluoroalkyl
      side chains at the surface of the PMMA(857)-ec-FMA(3.3) film was formed when the
      film was cast with benzotrifluoride solution, in which only unimers existed. This
      study indicates that such a solvent effect may be used to promote the formation
      of a well-ordered packing structure of the fluorinated moieties at the film
      surface. The ordering of the packing structure is to a certain extent more
      important than the content of the fluorinated moieties at the surface for
      improving the surface stability.

PMID- 18342325
TI  - Competitive solubilization of cholesterol and phytosterols in nonionic
      microemulsions studied by pulse gradient spin-echo NMR.
AB  - The actual mechanism of cholesterol reduction by phytosterols is yet to be
      explored. One hypothesis states that cholesterol and phytosterols compete on the
      solubilization locus within gastric bile salt micelles. In this study competitive
      solubilization within microemulsions as vehicles for dietary intake of
      cholesterol and phytosterols was studied by pulse gradient spin-echo nuclear
      magnetic resonance. The loaded microemulsions undergo phase transitions as a
      function of dilution, the type of solubilized sterol, and the weight ratio of the
      cosolubilized sterols. Microemulsions containing 10-20 wt% of aqueous phase, show
      similar diffusivity of the oil and aqueous phases in all examined systems
      (excluding PS-loaded one) reflecting the minor influence of these solubilizates
      on the structure of the inner and the outer phases. The closeness of these
      structures enables the mobility of water molecules between them. Upon further
      dilution (>20 wt% aqueous phase), significant differences in decrease rate of the
      oil and increase of the water phases mobilities (occurring upon inversion), were
      detected within the studied systems. It was concluded that the solubilized
      sterols influence the structural transitions based on their location within the
      structures and their competitive solubilization. The phytosterols solubilized
      mostly in the continuous oil phase and between the surfactant tails. Cholesterol
      is solubilized in the vicinity of the surfactant headgroups and affects the
      surface curvature. In mixtures of cholesterol and phytosterols, structural
      changes are dictated mostly by the presence of the cholesterol.

PMID- 18342326
TI  - Swollen and collapsed lyotropic lamellar rheology.
AB  - We have investigated linear rheological properties and the structure-flow
      relationship of the swollen (Lam(1)) and collapsed (Lam(2)) lamellar phases,
      formed on didodecyldimethylammonium bromide (DDAB)/lecithin/water ternary system
      at 25 degrees C. Both lamellar phases behaved like Bingham fluids and showed
      remarkable yield stresses. At rest the Lam(1) phase, which is characterized by
      densely packed vesicles whose sizes increase as the water content decreases in
      accordance to evolution of (2)H NMR spectral profiles of D(2)O, resulted in a
      strong elastic gel-like response. On the other hand, the Lam(2) phase, formed at
      high surfactant concentrations, showed a weak-gel viscoelasticity and (2)H NMR
      spectral patterns which are typical of planar bilayered structures. The increase
      of the quadrupole splitting as the water content decreases was assumed as a
      strong evidence of size increasing of the lamellar domains. We have demonstrated
      that by using dynamic rheology and the derived relaxation time spectra, along
      with (2)H NMR spectra of D(2)O, it is possible to differentiate between
      equilibrium lamellar structures occurring in a broad interval of total surfactant
      concentration. In addition, a shear-thickening regime, observed at intermediate
      shear-rate values, highlighted the onset of out-equilibrium lamellar structures
      which were present both on Lam(1) and Lam(2) phases.

PMID- 18342327
TI  - Shear-thickening flow of nanoparticle suspensions flocculated by polymer
      bridging.
AB  - The steady-shear viscosity, dynamic viscoelasticity, and stress relaxation
      behavior were measured for suspensions of silica nanoparticles dispersed in
      aqueous solutions of poly(ethylene oxide) (PEO). The suspensions of silica with
      diameters of 8-25 nm show striking shear-thickening profiles in steady shear and
      highly elastic responses under large strains in oscillatory shear. Since the
      silica particles are much smaller than the polymer coils, one molecule can extend
      through several particles by intrachain bridging. Each polymer coil may remain
      isolated as a floc unit and the silica particles hardly connect two flocs.
      Therefore, the flow of suspensions is Newtonian with low viscosity at low shear
      rates. When the polymer coils containing several nanoparticles are subjected to
      high shear fields, three-dimensional network is developed over the system. The
      shear-thickening flow may arise from the elastic forces of extended bridges. But,
      the polymer chain is easily detached from particle surface by thermal energy
      because of large curvature of particles. As a result, the network structures are
      reversibly broken down in a quiescent state and the suspensions behaves as
      viscoelastic fluids with the zero-shear viscosity.

PMID- 18342328
TI  - Short-term hardening effects on survival of acute and chronic cold exposure by
      Drosophila melanogaster larvae.
AB  - We quantified the variation and plasticity in cold tolerance among four larval
      stages of four laboratory strains of Drosophila melanogaster in response to both
      acute (<2h of cold exposure) and chronic ( approximately 7h of cold exposure)
      cold exposure. We observed significant differences in basal cold tolerance
      between the strains and among larval stages. Early larval instars were generally
      more tolerant of acute cold exposures than third-instar larvae. However,
      wandering larvae were more tolerant of chronic cold exposures than the other
      stages. Early stages also displayed a more pronounced rapid cold-hardening
      response than the later stages. Heat pre-treatment did not confer a significant
      increase in cold tolerance to any of the strains at any stage, pointing to
      different mechanisms being involved in resolving heat- and cold-elicited damage.
      However, when heat pre-treatment was combined with rapid cold-hardening as
      sequential pre-treatments, both positive (heat first) and negative (heat second)
      effects on cold tolerance were observed. We discuss possible mechanisms
      underlying cold-hardening and the effects of acute and chronic cold exposures.

PMID- 18342329
TI  - Is the social parasite Vespa dybowskii using chemical transparency to get her
      eggs accepted?
AB  - Both avian and insect cuckoos must trick their hosts into accepting foreign eggs.
      In birds this is achieved through egg mimicry. Within the hornets the only known
      social parasite is the rare Vespa dybowskii. We investigated how the V. dybowskii
      queen induces tens or hundreds of host workers to accept her eggs and offspring.
      Since hydrocarbons function as recognition cues in social insects, we
      investigated these compounds from the surface of eggs and workers of V.
      dybowskii, both host species (V. simillima and V. crabro) and an additional four
      non-host species. We found that chemical mimicry of the hosts' colony odour and
      their eggs normally associated with wasps was not being employed by V. dybowskii.
      Chemical insignificance is also unlikely as the amounts of hydrocarbons extracted
      from parasite, host and non-host eggs were similar. Eggs of V. dybowskii may
      survive in part due to being chemically transparent, as methyl-branched compounds
      only represent a tiny proportion (<1%) of the parasites hydrocarbon profile but a
      large proportion (26-41%) in both host species. However, the functions of various
      hydrocarbon groups need to be investigated in the hornets before this new
      acceptance mechanism of parasite eggs and adults is understood.

PMID- 18342330
TI  - Structural, biochemical, and in vivo characterization of the first virally
      encoded cyclophilin from the Mimivirus.
AB  - Although multiple viruses utilize host cell cyclophilins, including severe acute
      respiratory syndrome (SARS) and human immunodeficiency virus type-1(HIV-1), their
      role in infection is poorly understood. To help elucidate these roles, we have
      characterized the first virally encoded cyclophilin (mimicyp) derived from the
      largest virus discovered to date (the Mimivirus) that is also a causative agent
      of pneumonia in humans. Mimicyp adopts a typical cyclophilin-fold, yet it also
      forms trimers unlike any previously characterized homologue. Strikingly,
      immunofluorescence assays reveal that mimicyp localizes to the surface of the
      mature virion, as recently proposed for several viruses that recruit host cell
      cyclophilins such as SARS and HIV-1. Additionally mimicyp lacks peptidyl-prolyl
      isomerase activity in contrast to human cyclophilins. Thus, this study suggests
      that cyclophilins, whether recruited from host cells (i.e. HIV-1 and SARS) or
      virally encoded (i.e. Mimivirus), are localized on viral surfaces for at least a
      subset of viruses.

PMID- 18342331
TI  - Molecular determinants of substrate specificity in plant 5'-methylthioadenosine
      nucleosidases.
AB  - 5'-Methylthioadenosine (MTA)/S-adenosylhomocysteine (SAH) nucleosidase (MTAN) is
      essential for cellular metabolism and development in many bacterial species.
      While the enzyme is found in plants, plant MTANs appear to select for MTA
      preferentially, with little or no affinity for SAH. To understand what determines
      substrate specificity in this enzyme, MTAN homologues from Arabidopsis thaliana
      (AtMTAN1 and AtMTAN2, which are referred to as AtMTN1 and AtMTN2 in the plant
      literature) have been characterized kinetically. While both homologues hydrolyze
      MTA with comparable kinetic parameters, only AtMTAN2 shows activity towards SAH.
      AtMTAN2 also has higher catalytic activity towards other substrate analogues with
      longer 5'-substituents. The structures of apo AtMTAN1 and its complexes with the
      substrate- and transition-state-analogues, 5'-methylthiotubercidin and formycin
      A, respectively, have been determined at 2.0-1.8 A resolution. A homology model
      of AtMTAN2 was generated using the AtMTAN1 structures. Comparison of the AtMTAN1
      and AtMTAN2 structures reveals that only three residues in the active site differ
      between the two enzymes. Our analysis suggests that two of these residues,
      Leu181/Met168 and Phe148/Leu135 in AtMTAN1/AtMTAN2, likely account for the
      divergence in specificity of the enzymes. Comparison of the AtMTAN1 and available
      Escherichia coli MTAN (EcMTAN) structures suggests that a combination of
      differences in the 5'-alkylthio binding region and reduced conformational
      flexibility in the AtMTAN1 active site likely contribute to its reduced
      efficiency in binding substrate analogues with longer 5'-substituents. In
      addition, in contrast to EcMTAN, the active site of AtMTAN1 remains solvated in
      its ligand-bound forms. As the apparent pK(a) of an amino acid depends on its
      local environment, the putative catalytic acid Asp225 in AtMTAN1 may not be
      protonated at physiological pH and this suggests the transition state of AtMTAN1,
      like human MTA phosphorylase and Streptococcus pneumoniae MTAN, may be different
      from that found in EcMTAN.

PMID- 18342332
TI  - Fibril growth kinetics reveal a region of beta2-microglobulin important for
      nucleation and elongation of aggregation.
AB  - Amyloid is a highly ordered form of aggregate comprising long, straight and
      unbranched proteinaceous fibrils that are formed with characteristic nucleation
      dependent kinetics in vitro. Currently, the structural molecular mechanism of
      fibril nucleation and elongation is poorly understood. Here, we investigate the
      role of the sequence and structure of the initial monomeric precursor in
      determining the rates of nucleation and elongation of human beta(2)-microglobulin
      (beta(2)m). We describe the kinetics of seeded and spontaneous (unseeded) fibril
      growth of wild-type beta(2)m and 12 variants at pH 2.5, targeting specifically an
      aromatic-rich region of the polypeptide chain (residues 62-70) that has been
      predicted to be highly amyloidogenic. The results reveal the importance of
      aromatic residues in this part of the beta(2)m sequence in fibril formation under
      the conditions explored and show that this region of the polypeptide chain is
      involved in both the nucleation and the elongation phases of fibril formation.
      Structural analysis of the conformational properties of the unfolded monomer for
      each variant using NMR relaxation methods revealed that all variants contain
      significant non-random structure involving two hydrophobic clusters comprising
      regions 29-51 and 58-79, the extent of which is critically dependent on the
      sequence. No direct correlation was observed, however, between the extent of non
      random structure in the unfolded state and the rates of fibril nucleation and
      elongation, suggesting that the early stages of aggregation involve significant
      conformational changes from the initial unfolded state. Together, the data
      suggest a model for beta(2)m amyloid formation in which structurally specific
      interactions involving the highly hydrophobic and aromatic-rich region comprising
      residues 62-70 provide a complementary interface that is key to the generation of
      amyloid fibrils for this protein at acidic pH.

PMID- 18342333
TI  - Molecular mechanism of p73-mediated regulation of hepatitis B virus core
      promoter/enhancer II: implications for hepatocarcinogenesis.
AB  - Hepatitis B virus (HBV) is a causative agent of chronic hepatitis and
      hepatocellular carcinoma. Recent findings demonstrating p73 and specifically N
      terminally truncated p73 (DeltaTAp73) accumulation in hepatocellular carcinoma
      suggest that p73 plays a role in the malignant phenotype. Here, we investigated
      the mechanism of HBV pregenomic core promoter/enhancer II (cp/EII) regulation by
      full-length TAp73 and its oncogenic counterpart DeltaTAp73. Ectopic and
      endogenous expression of TAp73 leads to a significant downregulation of cp/EII
      activity in p53-deficient hepatoma cell lines. In contrast, overexpression of
      DeltaTAp73 results in significant cp/EII activation and increased HBV core (HBc)
      expression. TAp73-mediated repression of HBV transcription was substantially
      abolished by DeltaTAp73. We show that both TAp73 and DeltaTAp73 proteins directly
      bind to the Sp1 transcription factor, a key stimulator of HBV gene expression.
      However, only TAp73 abolishes Sp1 binding to cp/EII, whereas the DeltaTAp73-Sp1
      complex further persists on the DNA. The inhibitory effect of p53/p73 on HBc
      expression is associated with the inhibition of viral replication, while
      DeltaTAp73 is not. These data strongly support the fact that the p73-isoform
      related interaction with Sp1 is the underlying mechanism of the diverse outcome
      on HBc expression, suggesting a new mechanism by which oncogenic DeltaTAp73 could
      enhance the carcinogenic process in liver cells.

PMID- 18342334
TI  - Biochemical and structural analysis of substrate promiscuity in plant Mg2+
      dependent O-methyltransferases.
AB  - Plant S-adenosyl-l-methionine-dependent class I natural product O
      methyltransferases (OMTs), related to animal catechol OMTs, are dependent on
      bivalent cations and strictly specific for the meta position of aromatic vicinal
      dihydroxy groups. While the primary activity of these class I enzymes is
      methylation of caffeoyl coenzyme A OMTs, a distinct subset is able to methylate a
      wider range of substrates, characterized by the promiscuous phenylpropanoid and
      flavonoid OMT. The observed broad substrate specificity resides in two regions:
      the N-terminus and a variable insertion loop near the C-terminus, which displays
      the lowest degree of sequence conservation between the two subfamilies.
      Structural and biochemical data, based on site-directed mutagenesis and domain
      exchange between the two enzyme types, present evidence that only small
      topological changes among otherwise highly conserved 3-D structures are
      sufficient to differentiate between an enzymatic generalist and an enzymatic
      specialist in plant natural product methylation.

PMID- 18342335
TI  - Development of an outcome prediction measure for alcoholism therapy by multimodal
      monitoring of treatment processes.
AB  - Outcome prediction in alcoholism therapy is of major sociopolitical and economic
      significance. Instruments based on psychotherapeutic processes are lacking.
      Therefore, treatment processes of 64 chronic alcohol dependent patients have been
      investigated at three time-points, t(1) (week 3), t(2) (month 6), and t(3) (month
      12) during the first year of a comprehensive outpatient treatment program,
      guaranteeing strictly controlled alcohol abstinence. Main focus of the study was
      the prediction of cumulative abstinence probability over a follow-up period of up
      to 4 years based on these treatment processes. One hundred and seventy-five video
      recordings of therapy sessions were analyzed with the behavior observational
      system VAMP (Video-Assisted Monitoring of Psychotherapeutic Processes in Chronic
      Psychiatric Disease). Patients' self-rating of treatment processes was measured
      with questionnaires for self-efficacy, abstinence confidence, self-consciousness
      and stress coping. Prediction of cumulative abstinence probability was determined
      with Cox regression analysis. By integrating the observer rated process variables
      with the highest predictive validity, the composite score TOPPS (Therapy
      Orientation by Process Prediction Score) was constructed. It includes the process
      variables experience of resources, abstinence self-efficacy, implicit craving,
      relapse alertness, relapse risk, disease concept, dysfunctional therapeutic
      engagement, and dysfunctional problem solving of current problems. Whereas
      patients' self-rating of treatment processes was insufficiently predictive, the
      TOPPS strongly predicted four-year abstinence probability at any of the 3 time
      points (p<0.001). The results suggest to validate the item combination described
      in the TOPPS in addiction therapy as a treatment guideline of individual relapse
      prevention strategies.

PMID- 18342336
TI  - Remote protein homology detection using recurrence quantification analysis and
      amino acid physicochemical properties.
AB  - Remote homology detection refers to the detection of structure homology in
      evolutionarily related proteins with low sequence similarity. Supervised learning
      algorithms such as support vector machine (SVM) are currently the most accurate
      methods. In most of these SVM-based methods, efforts have been dedicated to
      developing new kernels to better use the pairwise alignment scores or sequence
      profiles. Moreover, amino acids' physicochemical properties are not generally
      used in the feature representation of protein sequences. In this article, we
      present a remote homology detection method that incorporates two novel features:
      (1) a protein's primary sequence is represented using amino acid's
      physicochemical properties and (2) the similarity between two proteins is
      measured using recurrence quantification analysis (RQA). An optimization scheme
      was developed to select different amino acid indices (up to 10 for a protein
      family) that are best to characterize the given protein family. The selected
      amino acid indices may enable us to draw better biological explanation of the
      protein family classification problem than using other alignment-based methods.
      An SVM-based classifier will then work on the space described by the RQA metrics.
      The classification scheme is named as SVM-RQA. Experiments at the superfamily
      level of the SCOP1.53 dataset show that, without using alignment or sequence
      profile information, the features generated from amino acid indices are able to
      produce results that are comparable to those obtained by the published state-of
      the-art SVM kernels. In the future, better prediction accuracies can be expected
      by combining the alignment-based features with our amino acids property-based
      features. Supplementary information including the raw dataset, the best
      performing amino acid indices for each protein family and the computed RQA
      metrics for all protein sequences can be downloaded from
      http://ym151113.ym.edu.tw/svm-rqa.

PMID- 18342337
TI  - Mating group size and evolutionarily stable pattern of sexuality in barnacles.
AB  - Barnacles, marine crustaceans, have various patterns of sexuality depending on
      species including simultaneous hermaphroditism, androdioecy (hermaphrodites and
      dwarf males), and dioecy (females and dwarf males). We develop a model that
      predicts the pattern of sexuality in barnacles by two key environmental factors:
      (i) food availability and (ii) the fraction of larvae that settle on the sea
      floor. Populations in the model consist of small individuals and large ones. We
      calculate the optimal resource allocation toward male function, female function
      and growth for small and large barnacles that maximizes each barnacle's lifetime
      reproductive success using dynamic programming. The pattern of sexuality is
      defined by the combination of the optimal resource allocations. In our model, the
      mating group size is a dependent variable and we found that sexuality pattern
      changes with the food availability through the mating group size: simultaneous
      hermaphroditism appears in food-rich environments, where the mating group size is
      large, protandric simultaneous hermaphroditism appears in intermediate food
      environments, where the mating group size also takes intermediate value, the
      other sexuality patterns, androdioecy, dioecy, and sex change are observed in
      food-poor environments, where the mating group size is small. Our model is the
      first one where small males can control their growth to large individuals, and
      hence has ability to explain a rich spectrum of sexual patterns found in
      barnacles.

PMID- 18342338
TI  - Potential use of mangroves as constructed wetland for municipal sewage treatment
      in Futian, Shenzhen, China.
AB  - A pilot-scale mangrove wetland was constructed in Futian, Shenzhen for municipal
      sewage treatment. Three identical belts (length: 33m, width: 3m, depth: 0.5m)
      were filled with stone (bottom), gravel and mangrove sand (surface). Seedlings of
      two native mangrove species (Kandelia candel, Aegiceras corniculatum) and one
      exotic species (Sonneratia caseolaris) were transplanted to the belts with one
      species for each belt. The hydraulic loading was 5m(3)d(-1) and hydraulic
      retention time 3d. High levels of removal of COD, BOD(5), TN, TP and NH(3)-N were
      obtained. The treatment efficiency of S. caseolaris and A. corniculatum was
      higher than that of K. candel. Faster plant growth was obtained for S.
      caseolaris. The substrate in the S. caseolaris belt also showed higher enzyme
      activities including dehydrogenase, cellulase, phosphatase, urease and beta
      glucosidase. The removal rates of organic matter and nutrients were positively
      correlated with plant growth. The results indicated that mangroves could be used
      in a constructed wetland for municipal sewage treatment, providing post-treatment
      to remove coliforms was also included.

PMID- 18342339
TI  - Impact of estrogenic compounds on DNA integrity in human spermatozoa: evidence
      for cross-linking and redox cycling activities.
AB  - A great deal of circumstantial evidence has linked DNA damage in human
      spermatozoa with adverse reproductive outcomes including reduced fertility and
      high rates of miscarriage. Although oxidative stress is thought to make a
      significant contribution to DNA damage in the male germ line, the factors
      responsible for creating this stress have not been elucidated. One group of
      compounds that are thought to be active in this context are the estrogens, either
      generated as a result of the endogenous metabolism of androgens within the male
      reproductive tract or gaining access to the latter as a consequence of
      environmental exposure. In this study, a wide variety of estrogenic compounds
      were assessed for their direct effects on human spermatozoa in vitro. DNA
      integrity was assessed using the Comet and TUNEL assays, lesion frequencies were
      quantified by QPCR using targets within the mitochondrial and nuclear (beta
      globin) genomes, DNA adducts were characterized by mass spectrometry and redox
      activity was monitored using dihydroethidium (DHE) as the probe. Of the
      estrogenic and estrogen analogue compounds evaluated, catechol estrogens,
      quercetin, diethylstilbestrol and pyrocatechol stimulated intense redox activity
      while genistein was only active at the highest doses tested. Other estrogens and
      estrogen analogues, such as 17beta-estradiol, nonylphenol, bisphenol A and 2,3
      dihydroxynaphthalene were inactive. Estrogen-induced redox activity was
      associated with a dramatic loss of motility and, in the case of 2
      hydroxyestradiol, the induction of significant DNA fragmentation. Mass
      spectrometry also indicated that catechol estrogens were capable of forming
      dimers that can cross-link the densely packed DNA strands in sperm chromatin,
      impairing nuclear decondensation. These results highlight the potential
      importance of estrogenic compounds in creating oxidative stress and DNA damage in
      the male germ line and suggest that further exploration of these compounds in the
      aetiology of male infertility is warranted.

PMID- 18342340
TI  - [Extra dural arachnoid cyst: case report].
AB  - Extradural arachnoid cysts are uncommon expanding lesions in the spinal canal,
      which may communicate with the subarachnoid space. Usually located in the lower
      thoracic spine, they may cause symptoms by compressing the spinal cord or nerve
      roots. We report a case of an extradural thoracic arachnoid cyst revealed by
      progressive spinal cord compression. CT myelography and MRI enabled diagnosis.
      Rapid neurological improvement was observed after surgical resection.

PMID- 18342341
TI  - Cognitive ability and continuous measures of relative hand skill: a note.
AB  - This note re-examines a finding by Crow et al. [Crow, T. J., Crow, L. R., Done,
      D. J., & Leask, S. (1998). Relative hand skill predicts academic ability: Global
      deficits at the point of hemispheric indecision. Neuropsychologia, 36(12), 1275
      1281] that equal skill of right and left hands is associated with deficits in
      cognitive ability. This is consistent with the idea that failure to develop
      dominance of one hemisphere is associated with various pathologies such as
      learning difficulties. Using the same data source but utilising additional data,
      evidence is found of a more complex relationship between cognitive ability and
      relative hand skill.

PMID- 18342342
TI  - Phonological short-term store impairment after cerebellar lesion: a single case
      study.
AB  - The cerebellum is a recent addition to the growing list of cerebral areas
      involved in the multifaceted structural system that sustains verbal working
      memory (vWM), but its contribution is still a matter of debate. Here, we present
      a patient with a selective deficit of vWM resulting from a bilateral cerebellar
      ischemic lesion. After this acute event, the patient had impaired immediate and
      delayed word-serial recall and auditory-verbal delayed recognition. The digit
      span, however, was completely preserved. To investigate the cerebellar
      contribution to vWM, four experiments addressing the function of different vWM
      phonological loop components were performed 18 months after the lesion, and
      results were compared with normative data or, when needed, with a small group of
      matched controls. In Experiment 1, digit span was assessed with different
      presentation and response modalities using lists of digits of varying lengths. In
      Experiment 2, the articulatory rehearsal system was analyzed by measurement of
      word length and articulatory suppression effects. Experiment 3 was devoted to
      analyzing the phonological short-term store (ph-STS) by the recency effect, the
      phonological similarity effect, short-term forgetting, and unattended speech.
      Data suggested a possible key role of the semantic component of the processed
      material, which was tested in Experiment 4, in which word and nonword-serial
      recall with or without interpolating activity were analyzed. The patient showed
      noticeably reduced scores in the tasks that primarily or exclusively engaged
      activity of the ph-STS, namely those of Experiment 3, and good performance in the
      tests that investigated the recirculation of verbal information. This pattern of
      results implicates the ph-STS as the cognitive locus of the patient's deficit.
      This report demonstrates a cerebellar role in encoding and/or strengthening the
      phonological traces in vWM.

PMID- 18342343
TI  - Attentional bias as trait: correlations with novelty seeking.
AB  - Pseudoneglect is traditionally viewed as reflecting right hemisphere
      specialization for processing spatial information, which brings about relatively
      greater activation of the right hemisphere and orienting towards the
      contralateral space. Such interpretation implies that the leftward attentional
      bias is a population trait. Animal studies, however, suggest that orienting bias
      is a trait of the individual and individual differences in the direction and
      magnitude of this orienting bias reflect individual differences in asymmetry in
      dopaminergic brain systems, which are also reflected in other behavioral
      differences. The present study was designed to test the hypothesis that healthy
      individuals show consistent attentional bias, the direction and magnitude of
      which varies among individuals and is associated with the degree of novelty
      seeking, a temperament trait associated with dopamine asymmetry. Forty-nine right
      handed participants performed the greyscales task on two separate occasions and
      completed the Tridimensional Personality Questionnaire. Although on average some
      degree of leftward attentional bias was observed on both occasions, both the
      direction and the magnitude of the bias differed greatly, with some individuals
      showing a strong leftward bias whereas others showed a strong rightward bias. A
      highly significant correlation was found between degree and magnitude of this
      bias on the two testing sessions, supporting the hypothesis that it may reflect
      an individual trait. As predicted, higher scores on novelty seeking were
      associated with rightward attentional bias, suggesting that this bias may reflect
      asymmetries in dopaminergic circuits in healthy individuals.

PMID- 18342344
TI  - Fingerprint profile of Ginkgo biloba nutritional supplements by LC/ESI-MS/MS.
AB  - Ginkgo biloba is one of the most popular herb nutrition supplements, with terpene
      lactones and flavonoids being the two major active components. A fingerprint
      profile method was developed using a capillary HPLC/MS method which can identify
      more than 70 components from the G. biloba product. The method allows the
      flavonoids and terpene lactones to be detected simultaneously and information of
      both the parent ion and its fragmentation can be obtained in just one HPLC/MS
      run. Targeted post-acquisition analysis allows mass spectrometric information
      regarding the identification of flavonoid components to be easily distinguished
      from other data, however the same approach for terpene lactones was less
      successful due to dimer formation and requires further development. The
      fingerprint profiles of five commercial G. biloba nutritional supplements were
      obtained and compared; variation of some components among the samples was
      observed and fortification could be detected. In the quality control analysis of
      the G. biloba product this method could be viewed as complementary to specific
      quantitative analysis of some bioactive components of the herb.

PMID- 18342345
TI  - Diversification of an ancient theme: hydroxynitrile glucosides.
AB  - Many plants produce cyanogenic glucosides as part of their chemical defense. They
      are alpha-hydroxynitrile glucosides, which release toxic hydrogen cyanide (HCN)
      upon cleavage by endogenous plant beta-glucosidases. In addition to cyanogenic
      glucosides, several plant species produce beta- and gamma-hydroxynitrile
      glucosides. These do not release HCN upon hydrolysis by beta-glucosidases and
      little is known about their biosynthesis and biological significance. We have
      isolated three beta-hydroxynitrile glucosides, namely (2Z)-2-(beta-D
      glucopyranosyloxy)but-2-enenitrile and (2R,3R)- and (2R,3S)-2-methyl-3-(beta-D
      glucopyranosyloxy)butanenitrile, from leaves of Ribesuva-crispa. These compounds
      have not been identified previously. We show that in several species of the
      genera Ribes, Rhodiola and Lotus, these beta-hydroxynitrile glucosides co-occur
      with the L-isoleucine-derived hydroxynitrile glucosides, lotaustralin (alpha
      hydroxynitrile glucoside), rhodiocyanosides A (gamma-hydroxynitrile glucoside)
      and D (beta-hydroxynitrile glucoside) and in some cases with sarmentosin (a
      hydroxylated rhodiocyanoside A). Radiolabelling experiments demonstrated that the
      hydroxynitrile glucosides in R. uva-crispa and Hordeum vulgare are derived from L
      isoleucine and L-leucine, respectively. Metabolite profiling of the natural
      variation in the content of cyanogenic glucosides and beta- and gamma
      hydroxynitrile glucosides in wild accessions of Lotus japonicus in combination
      with genetic crosses and analyses of the metabolite profile of the F2 population
      provided evidence that a single recessive genetic trait is most likely
      responsible for the presence or absence of beta- and gamma-hydroxynitrile
      glucosides in L. japonicus. Our findings strongly support the notion that the
      beta- and gamma-hydroxynitrile glucosides are produced by diversification of the
      cyanogenic glucoside biosynthetic pathway at the level of the nitrile
      intermediate.

PMID- 18342346
TI  - Biofilm-forming associated genotypic and phenotypic characteristics of
      Staphylococcus spp. isolated from animals and air.
AB  - Biological monitoring is performed to detect and analyze microorganisms that have
      continuously made an effort to survive in the environment. Of such
      microorganisms, Staphylococcus spp. is considered a common cause of nosocomial
      and environmental infections., Microbial Surface Components Recognizing Adhesive
      Matrix Molecules (MSCRAMMs) are required for the adhesion and biofilm formation
      of Staphylococci. Thirty-six and thirty-five Staphylococci isolated from animals
      and air, respectively, were analyzed. Biofilm formation and ten MSCRAMM genes
      were investigated using Congo red agar, tissue culture plate methods, and PCR.
      Airborne isolates were shown to have higher adherence and stronger biofilm
      formation than those from animals. The prevalence of MSCRAMM genes from air
      isolates was also higher than those from animals. Of the genes, eno was mainly
      associated with biofilm formation in both animals and airborne isolates (P<0.05).
      Moreover, the rate of airborne isolates harboring the eno gene was higher than in
      animal isolates. These results indicated that analysis of MSCRAMM genes with a
      phenotypic assay might be a helpful bacterial control system for the environment.

PMID- 18342347
TI  - [Botryoid odontogenic cyst].
AB  - INTRODUCTION: The botryoid odontogenic cyst (BOC) is a developmental cyst of
      odontogenic epithelial origin considered as a rare multilocular variety of
      lateral periodontal cyst (WHO 1992). This cystic lesion site is in the
      periodontal space of vital teeth. OBSERVATION: A 21-year-old woman consulted for
      a swelling of the anterior maxillary region. The clinical examination revealed
      bucal swelling extending from the left central incisor to the first left
      premolar. The mucosa was normal. The adjacent teeth were vital. X-ray revealed a
      bilocular radiolucency extending between the roots of teeth 21 and 24. The lesion
      was enucleated, under local anaesthesia via a vestibular approach. Histology was
      typical of a BOC with cystic spaces lined by squamous epithelium with thickening
      and clear cells. Forty-eight months after surgery, there was sign of recurrence.
      DISCUSSION: BOC is known to be a recurrent odontogenic cyst. Several cases of
      multiple recurrences have been reported up to nine years after the initial
      surgery. Long-term follow-up is thus mandatory.

PMID- 18342348
TI  - Rapid and estrogen receptor beta mediated actions in the hippocampus mediate some
      functional effects of estrogen.
AB  - The steroid hormone, estradiol (E(2)), has numerous targets in the central
      nervous system, including the hippocampus, which plays a key role in cognition
      and affective behavior. This review focuses on our evidence from studies in
      rodents that E(2) has diverse mechanisms in the hippocampus for its functional
      effects. E(2) has rapid, membrane-mediated effects in the hippocampus to enhance
      cognitive performance. Administration of E(2) to the hippocampus of rats for 10
      min following training enhances performance in a hippocampus-mediated task.
      Increased cell firing in the hippocampus occurs within this short-time frame.
      Furthermore, administration of free E(2) or an E(2) conjugate, E(2):bovine serum
      albumin (BSA), to the hippocampus produces similar performance-enhancing effects
      in this task, suggesting that E(2) has membrane actions in the hippocampus for
      these effects. Further evidence that E(2) has rapid, membrane-mediated effects is
      that co-administration of E(2) and inhibitors of mitogen-activated protein kinase
      (MAPK), rather than intracellular E(2) receptors (ERs) or protein synthesis,
      attenuate the enhancing effects of E(2) in this task. Despite these data that
      demonstrate E(2) can have rapid and/or membrane-mediated effects in the
      hippocampus, there is clear evidence to suggest that intracellular ERs,
      particularly the beta (rather than alpha) isoform of ERs, may be important
      targets for E(2)'s functional effects for hippocampal processes. Administration
      of ligands that are specific for ERbeta, but not ERalpha, have enhancing effects
      on hippocampal processes similar to that of E(2) (which has similar affinity for
      ERalpha and ERbeta). These effects are attenuated when ERbeta expression is
      knocked down in transgenic models or with central administration of antisense
      oligonucleotides. Thus, there may be a convergence of E(2)'s actions through
      rapid, membrane-mediated effects and intracellular ERs in the hippocampus for
      these functional effects.

PMID- 18342349
TI  - Modulation of hypothalamic neuronal activity through a novel G-protein-coupled
      estrogen membrane receptor.
AB  - Estrogens are involved in the hypothalamic control of multiple homeostatic
      functions including reproduction, stress responses, energy metabolism, sleep
      cycles, temperature regulation and motivated behaviors. The actions of 17beta
      estradiol (E(2)) in the brain have been attributed to the activation of estrogen
      receptors alpha and beta, as well as G-protein-coupled or other membrane
      associated estrogen receptors. Recently, we have identified a putative membrane
      associated estrogen receptor that is coupled to desensitization of GABA(B)
      receptors in guinea pig and mouse hypothalamic neurons including
      proopiomelanocortin (POMC) neurons. We have synthesized a new nonsteroidal
      compound, STX, which selectively targets the Galphaq-coupled phospholipase C
      protein kinase C-protein kinase A pathway, and have established that STX is more
      potent than E(2) in mediating this desensitization in an ICI 182,780-sensitive
      manner in both guinea pig and mouse neurons. Both E(2) and STX are fully
      efficacious in estrogen receptor alpha, beta knock-out mice. Finally, we observed
      that the putative membrane-associated estrogen receptor is different from GPR30
      in arcuate neurons using whole-cell patch recording in hypothalamic slices from
      GPR30 knock-out mice. Collectively, these findings suggest that the mER is
      distinct from ERalpha, ERbeta or GPR30.

PMID- 18342350
TI  - A microwave promoted and Lewis acid catalysed solventless approach to 4
      azasteroids.
AB  - The preparation of 3-oxo-4-azasteroid from A-nor-3,5-secosteroid-3-oic acid is
      described in a solventless condition catalysed by Lewis acid under microwave
      irradiation. We utilized urea as an environmentally benign source for the
      generation of ammonia for the aza cyclization reaction.

PMID- 18342352
TI  - Viral diversity limits immune diversity in asymptomatic phase of HIV infection.
AB  - We propose a new diversity threshold theory which states that the specific CTLs
      to the viral strain become inactivated (that is, some HIV strain can escape from
      its specific immune response) when the diversity of HIV strains exceeds some
      threshold number. We call this number "immune diversity threshold". Our theory
      can explain the inactivation of specific immune response and a limit of maximum
      immune diversity. We can conclude that the accumulation of viral diversity
      eventually leads to AIDS.

PMID- 18342351
TI  - Membrane actions of progestins at dopamine type 1-like and GABAA receptors
      involve downstream signal transduction pathways.
AB  - In the ventral tegmental area (VTA), progestins facilitate lordosis via rapid
      actions at membrane dopamine Type 1-like (D(1)) and/or GABA(A) receptors (GBRs),
      rather than via cognate, intracellular progestin receptors (PRs). Downstream
      signal transduction pathways involved in these effects were investigated using
      lordosis as a bioassay. If progestins' actions at D(1) and/or GBRs in the VTA
      require activation of G-proteins, adenylyl cyclase, cyclic AMP-dependent protein
      kinase A (PKA), phospholipase C (PLC), and/or PKC, then pharmacologically
      blocking these pathways would be expected to attenuate progestin-facilitated
      lordosis and its enhancement by D(1) and GBR activity. Ovariectomized, estradiol
      primed rats were infused first with vehicle or signal transduction inhibitor, and
      second with vehicle, a D(1) or GBR agonist, and then with vehicle or progestins
      to the VTA. Rats were tested for lordosis following infusions. Results indicated
      that initiation of G-proteins, adenylyl cyclase, PKA, PLC, or PKC in the VTA is
      required for rapid effects of progestins through D(1) and/or GBRs to facilitate
      lordosis. As well, progestins' actions at n-methyl-d-aspartate receptors (NMDARs)
      may modulate activity at D(1) and/or GBRs and mitogen activated protein kinase
      (MAPK) may be a common signaling pathway. Findings from a microarray study
      demonstrated that there was upregulation of genes associated with steroid
      metabolism, GBRs, D(1), NMDARs and signal transduction factors in the midbrain
      VTA of naturally receptive mated compared to non-mated rats. Thus, in the VTA,
      progestins have rapid membrane-mediated actions via D(1), GBRs, NMDARs and their
      downstream signal transduction pathways.

PMID- 18342353
TI  - Electron microscopic observations of the anterior pituitary gland. Part I. The
      neurons in the "transitional zone" of the anterior pituitary gland.
AB  - Since [Westlud, K.N., Chils, G.V., 1982. Localization of serotonin fibers in the
      rat adenohypophysis. Endocrinology 111, 1761-1763] initially identified the
      serotonin nerve fibers in the anterior pituitary gland, attention has been paid
      to the rostral zone of the anterior lobe into which nerve fibers enter and
      subsequently spread to deeper regions of the lobe. The rostral zone is the
      trifurcated junction of the partes tuberalis, intermedia and distalis, and has
      the important role(s) for hormone secretion via the "transitional zone" [Sato, G,
      Shirasawa, N, Sakuma, E, Sato, Y, Asai, Y, Wada, I, Horiuchi, O, Sakamoto, A,
      Herbert, DC, Soji, T, 2005a. Intercellular communications within the rat anterior
      pituitary. XI: An immunohistochemical study of distributions of S-100 positive
      cells in the anterior pituitary of the rat. Tissue and Cell 37, 269-280.]. The
      objective of this study was to focus on the ultrastructure of this "zone." All of
      the animals studied were fixed by perfusion with glutaraldehyde via the left
      ventricle of the heart and examined by electron microscopy. In the "transitional
      zone," a cluster of neuronal elements was observed between the folliculo-stellate
      cell-rich area and the anterior lobe. This cluster consisted of myelinated
      fibers, unmyelinated fibers, neuroendocrine fibers, large cells, and supporting
      cells. The large cells were perikarya of neurons which made a "ganglion-like"
      structure with associated satellite cells. Agranular, folliculo-stellate cells
      were intermingled among the elements. This is the first report that neuronal
      elements form clusters in the "transitional zone." A relationship of the
      unmyelinated and neuroendocrine fibers in the basal layer and in the
      "transitional zone" is discussed.

PMID- 18342354
TI  - Proteomic assessment of sulfur mustard-induced protein adducts and other protein
      modifications in human epidermal keratinocytes.
AB  - Although some toxicological mechanisms of sulfur mustard (HD) have been
      uncovered, new knowledge will allow for advanced insight in the pathways that
      lead towards epidermal-dermal separation in skin. In the present investigation,
      we aimed to survey events that occur at the protein level in human epidermal
      keratinocytes (HEK) during 24 h after exposure to HD. By using radiolabeled (14)C
      HD, it was found that proteins in cultured HEK are significant targets for
      alkylation by HD. HD-adducted proteins were visualized by two-dimensional gel
      electrophoresis and analyzed by mass spectrometry. Several type I and II
      cytokeratins, actin, stratifin (14-3-3sigma) and galectin-7 were identified.
      These proteins are involved in the maintenance of the cellular cytoskeleton.
      Their alkylation may cause changes in the cellular architecture and, in direct
      line with that, be determinative for the onset of vesication. Furthermore,
      differential proteomic analysis was applied to search for novel features of the
      cellular response to HD. Partial breakdown of type I cytokeratins K14, K16 and
      K17 as well as the emergence of new charge variants of the proteins heat shock
      protein 27 and ribosomal protein P0 were observed. Studies with caspase
      inhibitors showed that caspase-6 is probably responsible for the breakdown of
      type I cytokeratins in HEK. The significance of the results is discussed in terms
      of toxicological relevance and possible clues for therapeutic intervention.

PMID- 18342355
TI  - Pharmacokinetics of tetrodotoxin in puffer fish Takifugu rubripes by a single
      administration technique.
AB  - Marine puffer fish accumulates tetrodotoxin (TTX) in the liver and ovary. In this
      study, we examined the pharmacokinetics of TTX in Takifugu rubripes by a single
      administration under general anesthesia at 20 degrees C for 300 min. The blood
      concentration-time profile showed multiple distinct phases after injection into
      hepatic portal vein. The area under the blood concentration-time curve (AUC)
      increased linearly at the dosage of 0.25-0.75 mg TTX/kg body weight, and the
      total body clearance was 2.06+/-0.17 mL/min/kg body weight. The AUCs following
      administration into the hepatic portal vein and hepatic vein were closely similar
      (147+/-33 versus 141+/-1 ng.min/microL), indicating negligible hepatic first-pass
      effect. Comparison of the AUCs following an administration to the hepatic vein
      and gastrointestinal tract (0.25 mg TTX/kg body weight) elucidated the
      bioavailability of TTX to be 62%. There was no significant increase in the AUCs
      following direct injection into the gastrointestinal tract (0.50 versus 1.0 mg
      TTX/kg body weight). At the dosage of 0.25 mg TTX/kg body weight into the hepatic
      vein, hepatic portal vein or gastrointestinal tract, TTX amount in the liver
      accounted for 84+/-6%, 70+/-9% or 49+/-17% of the total TTX amount applied,
      respectively. These results demonstrate that TTX is absorbed into the systemic
      circulation from the gastrointestinal tract by saturable mechanism and finally
      accumulated in the liver within 300 min.

PMID- 18342356
TI  - Effects of cooking and heat treatment on concentration and tissue distribution of
      okadaic acid and dinophysistoxin-2 in mussels (Mytilus edulis).
AB  - Using high-performance liquid chromatography with mass spectrometry, the
      influence of conventional steaming and another heat treatment on the level of
      okadaic acid and dinophysistoxin-2 in mussels (Mytilus edulis) was investigated.
      Concentration increases correlated with water loss during steaming, and increased
      distribution of okadaic acid and dinophysistoxin-2 from the digestive glands to
      the remainder tissues was observed as a result of the processes examined. This
      suggests that the analysis of whole flesh tissues, as opposed to dissected
      digestive glands, is more appropriate for regulatory purposes, particularly if
      cooked samples are being analysed. A systematic heat treatment experiment showed
      that while okadaic acid group toxins are stable during cooking processes,
      degradation does occur in mussel tissues after prolonged exposure to high
      temperatures. The findings of the studies reported here have importance in terms
      of the methodology applied in regulatory phycotoxin monitoring programmes.
      Therefore, options for sample pretreatment are discussed.

PMID- 18342357
TI  - Event-based size distributions of particulate matter transported during urban
      rainfall-runoff events.
AB  - Source area rainfall-runoff conveyances are capable of mobilizing and
      transporting a very hetero-disperse size gradation of particulate matter (PM).
      This PM is most commonly characterized through a single event-based gravimetric
      index such as total suspended solids (TSS) or suspended sediment concentration
      (SSC) without an examination of PM fractions or particle size distributions
      (PSDs). Recognizing the utility of such indices, this study went further to
      examine PM suspended-settleable-sediment fractions and PSDs to representatively
      characterize the entire event-based PSD of the PM non-colloidal fractions from 1
      microm to larger than 24,500 microm transported by urban source area runoff
      events. This study examined the hetero-disperse PSD, and provided a mass balance
      analysis to ensure representative event-based results. On an event basis, fine PM
      (<75 microm; the suspended and settleable fractions) accounted for from 25% to
      80% of the gradation on a mass basis, and gravel-size PM (>2000 microm) ranged
      from 0.5% to 30%. Measured PSDs were compared to literature PSDs on paved
      surfaces, and in urban runoff from paved surfaces as well as the associated
      sampling and analysis methods. Results indicate that published urban street
      surface PSDs are generally within a similar range, with wider variability for
      published runoff PSDs. PSD variability is attributed to differences in sampling
      and analytical methods between studies. Knowledge of PSDs is critical for PM
      transport and fate, pollutant partitioning and distribution, as well as the non
      stationary behavior of unit operations.

PMID- 18342358
TI  - Arsenic removal from water employing heterogeneous photocatalysis with TiO2
      immobilized in PET bottles.
AB  - Arsenic oxidation (As(III) to As(V)) and As(V) removal from water were assessed
      by using TiO2 immobilized in PET (polyethylene terephthalate) bottles in the
      presence of natural sunlight and iron salts. The effect of many parameters was
      sequentially studied: TiO2 concentration of the coating solution, Fe(II)
      concentration, pH, solar irradiation time; dissolved organic carbon
      concentration. The final conditions (TiO2 concentration of the coating solution:
      10%; Fe(II): 7.0 mg l(-1); solar exposure time: 120 min) were applied to natural
      water samples spiked with 500 microg l(-1) As(III) in order to verify the
      influence of natural water matrix. After treatment, As(III) and total As
      concentrations were lower than the limit of quantitation (2 microg l(-1)) of the
      voltammetric method used, showing a removal over 99%, and giving evidence that
      As(III) was effectively oxidized to As(V). The results obtained demonstrated that
      TiO2 can be easily immobilized on a PET surface in order to perform As(III)
      oxidation in water and that this TiO2 immobilization, combined with
      coprecipitation of arsenic on Fe(III) hydroxides(oxides) could be an efficient
      way for inorganic arsenic removal from groundwaters.

PMID- 18342359
TI  - Use of highly sensitive sublethal stress responses in the social amoeba
      Dictyostelium discoideum for an assessment of freshwater quality.
AB  - In this work, the sensitivity of a battery of tests on the social amoeba
      Dictyostelium discoideum has been assessed within a freshwater toxicity study.
      The results obtained from the evaluation of survival and replication rate of D.
      discoideum were compared to those derived with a series of widely used tests for
      freshwater toxicity assessment, i. e. bioassays using Vibrio fischeri, Daphnia
      magna and Pseudokirchneriella subcapitata. The effects on sublethal endpoints,
      i.e. lysosomal membrane stability (LMS) and endocytotic rate, were analysed in
      conjunction with high-level endpoints to verify the potential to make a typical
      bioassay more sensitive. The field ecotoxicological investigation employing D.
      discoideum is part of a monitoring study assessing environmental quality of the
      Bormida River (Italy), subjected until recently to a chronic industrial
      pollution. The survey was carried out at several stations (upstream and
      downstream of a chemical factory outlet) in two different periods. In 2002, the
      results of chemical analyses performed on river water indicated no contamination.
      The ecotoxicological data obtained in this period showed that no evidence of
      biological effects was observed using V. fischeri and D. magna bioassays. In
      spite of the previous classical acute toxicity tests, significant differences in
      cell viability of D. discoideum were found. By analysing the effects measured on
      LMS and endocytotic rate, more relevant changes were observed for these sublethal
      stress biomarkers compared to survival. The chronic toxicity data showed
      significant changes in cell growth both of P. subcapitata and D. discoideum.
      Nevertheless, more sensitive and rapid responses were obtained when assessing the
      effects of exposure on D. discoideum. The chemical and ecotoxicological data
      obtained in 2006 indicated a full recovery of the quality of the river water
      (neither contamination nor toxicity found). Altogether, the results reported in
      this study underline that the use of a battery of biomarkers in conjunction with
      high-level endpoints may help follow the pollutant-induced stress syndrome in the
      organisms from early sublethal effects to starting mortality.

PMID- 18342360
TI  - Overriding the blockade of antinociceptive actions of opioids in rats treated
      with extended-release naltrexone.
AB  - A monthly extended-release formulation of the opioid antagonist naltrexone (XR
      NTX) is approved for treatment of alcohol dependence. There is little research
      regarding overriding chronic (>21 days) competitive opioid receptor blockade with
      opioids for acute pain. Using the hot plate test after XR-NTX or placebo
      microsphere administration, rats were treated with an opioid analgesic to
      determine the dose required to produce the maximum response latency (MRL; 60 s).
      Rats were later treated with the same opioid to determine any potential effects
      on respiration rate or locomotor activity. In naive rats, 15 mg/kg morphine, 0.1
      mg/kg fentanyl and 8 mg/kg hydrocodone produced MRL. In XR-NTX treated rats,
      morphine produced 36% and 46% MRL at 90 mg/kg on days 4 and 19 and 96% MRL at 45
      mg/kg on day 39. Fentanyl produced 100% MRL at 2.0 mg/kg on days 4 and 19 and at
      0.5 mg/kg on day 39. Hydrocodone (80 mg/kg) produced 69%, 80% and 100% MRL on
      days 4, 19 and 39. Compared to placebo, these doses did not further depress
      respiration or alter locomotor activity. Thus, opioid receptor blockade with XR
      NTX can be overcome in rats with higher doses of opioids without further
      affecting respiration or locomotor activity.

PMID- 18342361
TI  - Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5'
      terminal nucleotide.
AB  - Argonaute (AGO) proteins recruit small RNAs to form the core of RNAi effector
      complexes. Arabidopsis encodes ten AGO proteins and a large network of small
      RNAs. How these small RNAs are sorted into specific AGO complexes remains largely
      unknown. We have cataloged small RNAs resident in four AGO complexes. We found
      that AGO2 and AGO4 preferentially recruit small RNAs with a 5' terminal
      adenosine, whereas AGO1 harbors microRNAs (miRNAs) that favor a 5' terminal
      uridine. AGO5 predominantly binds small RNAs that initiate with cytosine.
      Changing the 5' terminal nucleotide of an miRNA predictably redirected it into a
      different AGO complex and alters its biological activity. These results reveal a
      role for small RNA sequences in assorting among AGO complexes. This suggests that
      specialization of AGO complexes might involve remodeling the 5' end-binding
      pocket to accept certain small RNA sequences, perhaps explaining the evolutionary
      drive for miRNAs to initiate with uridine.

PMID- 18342362
TI  - Specificity of ARGONAUTE7-miR390 interaction and dual functionality in TAS3 trans
      acting siRNA formation.
AB  - Trans-acting siRNA form through a refined RNAi mechanism in plants. miRNA-guided
      cleavage triggers entry of precursor transcripts into an RNA-DEPENDENT RNA
      POLYMERASE6 pathway, and sets the register for phased tasiRNA formation by DICER
      LIKE4. Here, we show that miR390-ARGONAUTE7 complexes function in distinct
      cleavage or noncleavage modes at two target sites in TAS3a transcripts. The AGO7
      cleavage, but not the noncleavage, function could be provided by AGO1, the
      dominant miRNA-associated AGO, but only when AGO1 was guided to a modified target
      site through an alternate miRNA. AGO7 was highly selective for interaction with
      miR390, and miR390 in turn was excluded from association with AGO1 due entirely
      to an incompatible 5' adenosine. Analysis of AGO1, AGO2, and AGO7 revealed a
      potent 5' nucleotide discrimination function for some, although not all,
      ARGONAUTEs. miR390 and AGO7, therefore, evolved as a highly specific miRNA
      guide/effector protein pair to function at two distinct tasiRNA biogenesis steps.

PMID- 18342363
TI  - Degree of conversion of resin blends in relation to ethanol content and
      hydrophilicity.
AB  - OBJECTIVES: To evaluate the degree of conversion of five experimental adhesive
      systems in relation to their hydrophilicity. The resin blends ranged from
      hydrophobic to hydrophilic and were tested as neat bonding agents, or solvated
      with increasing percentages of ethanol. The hypothesis tested was that extent of
      polymerization of resin blends is affected by resin hydrophilicity, solvent
      concentrations or time of polymerization. METHODS: Five light-curing versions of
      neat experimental resin blends were submitted to investigation: (1) 70% E-BisADM,
      28.75% TEGDMA; (2) 70% BisGMA, 28.7% TEGDMA; (3) 70% BisGMA, 28.7% HEMA; (4) 40%
      BisGMA, 30% TCDM, and 28.75% TEGDMA; (5) 40% BisGMA, 30% BisMP, and 28.75% HEMA.
      All blends included 1% EDMAB and 0.25% CQ. Ethanol in different weight
      percentages (A: 0%, B: 30%, C: 50%, D: 70% and E: 90%) was added to these resin
      blends simulating different formulation of adhesives. A differential scanning
      calorimeter was used to measure the degree of conversion of resin blends as a
      function of resin hydrophilicity, solvent concentration and time of curing. Data
      were analyzed with three-way ANOVA and Tukey's post hoc test. RESULTS: Exotherms
      showed that degree of conversion was influenced by the hydrophilicity of the
      blends resin (p<.05), percentage of ethanol dilution (p<.05) and time of curing
      (p<.05). 30% ethanol dilution increased degree of conversion compared to neat
      compounds irrespective to resin type and curing time, showing the highest degree
      of conversion values of the study design. SIGNIFICANCE: This study supports the
      hypothesis that high ethanol percentages (>50mass%) may compromise extent of
      polymerization kinetics of dental adhesives.

PMID- 18342364
TI  - Quantitative immunochemical evaluation of fish metallothionein upon exposure to
      cadmium.
AB  - Efficient implementation of an environmental biomarker requires multi-annual
      comparability over a wide geographical range. The present study improved the
      comparability of a quantitative competitive metallothionein (MT) enzyme-linked
      immuno-sorbent-assay (ELISA) in the sentinel fish Lithognathus mormyrus by
      introducing to the assay recombinant MT and beta-actin standards. Commercial
      antibodies for cod MT and mammalian actin were implemented. In addition, a
      sensitive anti L. mormyrus MT antibody was produced, adequate only for solid
      phase immunochemical assays. Cadmium was applied to the fish through injection
      and feeding to serve as a testing platform of the ELISA. The results demonstrated
      high potential protective capacity of the liver against toxic levels of
      transition metals through increasing MT levels. MT transcript levels were
      evaluated also from fish sampled at polluted and relatively clean natural sites,
      indicating applicability of MT as biomarker of exposure to a multi-factorial
      pollution, in comparison to its low revealed sensitivity to controlled cadmium
      exposure.

PMID- 18342365
TI  - Changes in amphipod (Crustacea) assemblages associated with shallow-water algal
      habitats invaded by Caulerpa racemosa var. cylindracea in the western
      Mediterranean Sea.
AB  - The effects of the invasive species Caulerpa racemosa var. cylindracea (hereafter
      C. racemosa) on amphipod assemblages associated with shallow-water rocky habitats
      were studied. Two habitats located along the SE Iberian Peninsula were compared;
      invaded and non-invaded. The results showed that growth of C. racemosa affects
      habitat structure, influencing the species composition and biomass of macroalgae,
      and detritus accumulation. In turn, such changes in habitat features affected the
      associated amphipod assemblages with different ecological requirements. However,
      the species richness of amphipods was relatively high in both habitats, while the
      species composition of amphipods changed completely. For example, some species
      such as Ampithoe ramondi and Hyale schmidti did not colonize invaded habitats,
      while others such as Apocorophium acutum were favoured by the spread of C.
      racemosa. Habitat invasion by C. racemosa can have an important influence on
      biotic assemblages, modifying both habitat structure and the associated fauna,
      with unknown effects on the overall ecosystem.

PMID- 18342366
TI  - The effects of matrix stiffness and RhoA on the phenotypic plasticity of smooth
      muscle cells in a 3-D biosynthetic hydrogel system.
AB  - Studies using 2-D cultures have shown that the mechanical properties of the
      extracellular matrix (ECM) influence cell migration, spreading, proliferation,
      and differentiation; however, cellular mechanosensing in 3-D remains under
      explored. To investigate this topic, a unique biomaterial system based on
      poly(ethylene glycol)-conjugated fibrinogen was adapted to study phenotypic
      plasticity in smooth muscle cells (SMCs) as a function of ECM mechanics in 3-D.
      Tuning the compressive modulus between 448 and 5804 Pa modestly regulated SMC
      cytoskeletal assembly in 3-D, with spread cells in stiff matrices having a
      slightly higher degree of F-actin bundling after prolonged culture. However,
      vinculin expression in all 3-D conditions was qualitatively low and was not
      assembled into the classic focal adhesions typically seen in 2-D cultures. Given
      the evidence that RhoA-mediated cytoskeletal contractility represents a critical
      node in mechanosensing, we molecularly upregulated contractility by inducing SMCs
      to express constitutively active RhoA. In these cells, F-actin bundling and total
      vinculin expression increased, and focal adhesion-like structures began to
      emerge, consistent with RhoA's mechanism of action in cells cultured on 2-D
      substrates. Furthermore, SMC proliferation in 3-D did not depend significantly on
      matrix stiffness, and was reduced by constitutive activation of RhoA irrespective
      of ECM mechanical properties. Conversely, the expression of contractile markers
      globally increased with constitutive RhoA activation and depended on 3-D matrix
      stiffness only in cells with heightened RhoA activity. Combined, these data
      suggest that the synergistic effects of ECM mechanics and RhoA activity on SMC
      phenotype in 3-D are distinct from those in 2-D, and highlight the importance of
      studying the mechanical role of cell-matrix interactions in tunable 3-D
      environments.

PMID- 18342367
TI  - Individually programmable cell stretching microwell arrays actuated by a Braille
      display.
AB  - Cell culture systems are often static and are therefore nonphysiological. In
      vivo, many cells are exposed to dynamic surroundings that stimulate cellular
      responses in a process known as mechanotransduction. To recreate this
      environment, stretchable cell culture substrate systems have been developed,
      however, these systems are limited by being macroscopic and low throughput. We
      have developed a device consisting of 24 miniature cell stretching chambers with
      flexible bottom membranes that are deformed using the computer-controlled,
      piezoelectrically actuated pins of a Braille display. We have also developed
      efficient image capture and analysis protocols to quantify morphological
      responses of the cells to applied strain. Human dermal microvascular endothelial
      cells (HDMECs) were found to show increasing degrees of alignment and elongation
      perpendicular to the radial strain in response to cyclic stretch at increasing
      frequencies of 0.2, 1, and 5 Hz, after 2, 4, and 12h. Mouse myogenic C2C12 cells
      were also found to align in response to the stretch, while A549 human lung
      adenocarcinoma epithelial cells did not respond to stretch.

PMID- 18342368
TI  - Hypoxia inducible factor 1 alpha regulates matrigel-induced endovascular
      differentiation under normoxia in a human extravillous trophoblast cell line.
AB  - Extravillous trophoblast (EVT) cells mimic endothelial cells during angiogenesis,
      inducing remodeling of the spiral arteries that increases blood flow toward the
      intravillous space. We have previously shown that signals involving the vascular
      endothelial growth factor (VEGF) axis are essential for endovascular
      differentiation through integrin signaling from the extracellular matrix: This
      was accomplished with use of the human EVT cell line TCL1, which shows tube
      formation that specifically recalls morphological changes in endothelial cells.
      To investigate endovascular differentiation in EVT further, we investigated the
      role of hypoxia inducible factor (HIF)1A, a subunit of HIF1 transcription factor
      that regulates not only adaptive responses to hypoxia, but also many cellular
      functions under normoxia, which was up-regulated in DNA microarray analysis
      during matrigel-induced endovascular differentiation under normoxia. HIF1A
      induces VEGF and ITGAV/ITGB3 aggregation, actions known to be important for
      cellular survival and endovascular differentiation in EVT. Inhibition of HIF1A up
      regulation using siRNA introduction or chemical inhibition suppressed hypoxia
      responsive element transcriptional activity, VEGF induction, ITGAV/ITGB3
      aggregation accompanied by the inhibition of tube formation in TCL1 cells. These
      results suggest that HIF1A has a crucial role in regulating EVT behavior
      including matrigel-induced endovascular differentiation under normoxia.

PMID- 18342370
TI  - Neoliberalism and its implications for mental health in the UK.
AB  - This article sets out to outline the tenets of neoliberalism and globalization,
      prior to the identification of the implications of neoliberalism for the British
      health system since 1979. The article then focuses on the applications and
      implications of neoliberalism for the British mental health system in terms of
      service organization and management, and the impact these changes in direction
      had on the three existing service sectors: users, carers and professionals. The
      discussion and the conclusion highlight the significance of these developments in
      the mental health system in the rather hybrid context of health, mental health,
      and social care policy and practice in the United Kingdom.

PMID- 18342371
TI  - Gaze following among toddlers.
AB  - Children's cooperative activities with their peers become markedly coordinated
      during the 3rd year of life. During these activities, the child needs to follow
      his/her peers' gaze to objects, and look at the same objects to initiate
      coordinated action. Since 3-year-olds' ability to follow their peers' gaze has
      not been studied, we experimentally investigated this in our study. In the
      experimental trials, an experimenter induced a child (looker) to look at a doll
      on display, and observed the reaction of another child (follower) who was in
      front of the looker (and not looking at the doll). In the control trials, the
      experimenter displayed the doll in an identical manner when the follower was
      alone. The followers followed the gaze of the lookers, looking at the doll in
      approximately 90% of the experimental trials, compared with 20% of the control
      trials. These results indicate that 3-year-olds can follow their peers' gaze.

PMID- 18342372
TI  - Role of DNA dynamics in Alzheimer's disease.
AB  - DNA is a dynamic molecule, the conformation of which plays a major role in
      biological function. The non-B-form of DNA conformations are reported in the
      patho-physiology of diseases like Fragile X-syndrome, Huntington's chorea,
      Alzheimer's and others. Recently, our laboratory discovered the presence of Z-DNA
      in the hippocampal region of severely affected Alzheimer's disease (AD) brain
      samples. Alternate purine-pyrimidine bases, potential sequences adopting Z-DNA,
      are present in the promoter regions of AD specific genes like amyloid precursor
      protein (APP), Presenilin and ApoE. Thus, Z-DNA might be involved in the
      expression of these pathologically important genes. In the present review, we
      have focused on the possible mechanisms/hypothetical models of Z-DNA transition
      and its implications in AD. We propose that Z-DNA is formed in the promoter
      region of the APP, and Presenilin genes and Z-DNA may absorb the negative
      supercoils at that region. This decreases the supercoil density, altering the
      domain's native supercoiling state and facilitates the binding of effectors,
      which positively regulate gene expression of AD-related genes like APP and
      Presenilin. Further, it is presumed that Z-DNA may be involved in the down
      regulation of genes involved in Abeta clearance, anti-oxidant and defense
      mechanisms in AD. The proposed working model is novel and reveals possible
      triggering factors or precursors, which regulate the modulation of the
      supercoiling level of DNA involving putative Z-DNA forming sequences and
      regulatory proteins binding to DNA in AD.

PMID- 18342373
TI  - Long-term eye movement recordings with a scleral search coil-eyelid protection
      device allows new applications.
AB  - The search coil technique is regarded as the gold standard in eye movement
      recordings. The manufacturers of scleral search coils (SSC) do not recommend
      using them longer than 30 min. The temporal limitations result from potential
      cornea damage and from irritations of the lid margins and palpebral conjunctiva
      which subjects perceive as unpleasant. Here we introduce a new coil-eyelid
      protection device (CEPD) which allows recording intervals up to 2 h with
      considerably reduced discomfort. Ophthalmic examinations and saccade recordings
      were used for comparison with the conventional SSC recording technique. In three
      experiments subjects were examined using SSCs with a commercially available
      cornea bandage lens on top of the search coil up to 120 min recording time.
      Ophthalmic testing revealed no apparent harmful effects on eyes or lid surface.
      Saccade parameters (main sequence) remained unchanged comparing SSC and CEPD
      recordings. Subjects rated less discomfort by using the CEPD. For the first time
      we show that SSC recordings can be extended over about 120 min without hazard to
      the eye, when using an eyelid protection lens. This advanced method allows new
      applications like eye movement recordings during sleep (rapid eye movements) or
      perceptional or motor learning tasks, e.g. saccade adaptation paradigms.

PMID- 18342374
TI  - HPT axis, CSF monoamine metabolites, suicide intent and depression severity in
      male suicide attempters.
AB  - A lower thyroid-stimulating hormone (TSH) response to thyrotropin-releasing
      hormone (TRH) in depressed women has been associated with violent suicide
      attempts, suicidal intent, higher lethality and suicide risk. The cerebrospinal
      fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA)
      levels are related to suicidal behaviour. We studied the HPT axis function in
      twelve male suicide attempters and eight healthy volunteers submitted to lumbar
      puncture and to TRH test. Suicidal behaviour and depression severity were
      assessed. There was no association between deltamaxTSH and violent suicidality or
      subsequent suicide. The deltamaxTSH correlated with CSF HVA in suicide
      attempters. The plasma T3 showed a negative correlation with the Beck Suicide
      Intent Scale and the Montgomery Asberg Depression rating scale. Dopaminergic
      regulatory mechanisms on the thyroid hormone activity may be altered in male
      suicide attempters.

PMID- 18342375
TI  - Is feline foamy virus really apathogenic?
AB  - Feline foamy virus (FFV) is a retrovirus commonly found in cats. It is generally
      thought to be apathogenic, making it a suitable candidate as a gene therapy
      vector. However, there have been reports of association of FFV with chronic
      progressive arthritis and a cofactor effect with feline immunodeficiency virus.
      This study investigated experimental FFV infection and whether this was
      associated with signs of disease. Eight young specific pathogen free cats were
      inoculated intramuscularly with FFV. The cats were examined twice weekly and
      blood and pharyngeal samples were taken. Haematology, biochemistry and FFV
      quantitative polymerase chain reaction (qPCR) were performed. Tissue samples were
      also collected throughout the six month period. FFV was initially detected by
      qPCR in the blood within the first two weeks of infection and viraemia persisted
      throughout the study. Two peaks of viraemia were observed, at day 20 (80
      170FFU/ml blood) and day 155 (332-415FFU/ml blood). FFV was also consistently
      detected in oropharyngeal samples after day 36. Anti-FFV IgG was detected in all
      cats by ELISA; antibody levels had an early peak around day 35 and then increased
      again following the second rise in circulating viral load. All cats remained
      clinically normal, except for one cat with an unrelated gingivitis. None of the
      cats developed pyrexia. The biochemical profile and blood cell counts remained
      within normal limits except for one cat with a persistent eosinophilia. Initial
      fluctuations in white cell counts settled within three weeks and did not deviate
      outside of the normal ranges. All tissue samples contained FFV DNA;
      lymphoreticular tissues, salivary gland and lung had the highest viral loads.
      Although there were no gross pathological lesions on post mortem examination,
      histologically a mild glomerulonephritis and a moderate interstitial pneumonia
      were observed in all cats. We conclude that during the six month period of
      infection, although cats appeared clinically normal, histopathological changes
      were observed in the lungs and kidneys. Further investigation of the significance
      of these changes is warranted before FFV is developed as a vector for gene
      delivery.

PMID- 18342376
TI  - The Wnt/frizzled/GSK-3 beta pathway: a novel therapeutic target for cardiac
      hypertrophy.
AB  - An excessive hypertrophic response of the heart to an increased workload is a
      leading cause of heart failure. At present, cardiac hypertrophy is treated with
      inhibitors of the renin-angiotensin system or with beta-adrenoceptor antagonists.
      These current therapeutic strategies inhibit prohypertrophic signaling pathways,
      but this therapy is inadequate in a substantial number of patients. However, the
      hypertrophic response of the heart is the net result of activation of
      prohypertrophic and antihypertrophic pathways. Glycogen synthase kinase-3 beta
      (GSK-3 beta) has a powerful antihypertrophic effect, but is inhibited by growth
      factors and hypertrophic stimuli through phosphorylation at the Ser9 residue of
      GSK-3 beta. Activation of the Wnt/frizzled pathway also results in inactivation
      of GSK-3 beta through sequestration of the kinase rather than phosphorylation at
      Ser9. In this Opinion article we will review the current evidence for the
      involvement of Wnt/frizzled signaling and the activation of GSK-3 beta in the
      regulation of cardiac hypertrophy, and subsequently discuss the potential of this
      pathway to serve as a novel therapeutic approach for cardiac hypertrophy.

PMID- 18342377
TI  - Rapid and sensitive detection of ostreid herpesvirus 1 in oyster samples by real
      time PCR.
AB  - Herpes and herpes-like virus infections have been reported in various marine
      mollusc species associated with high mortality rates. Following the
      characterisation and genome sequencing of ostreid herpesvirus 1 (OsHV-1),
      specific diagnostic tools have been developed based on conventional PCR
      techniques or in situ hybridisation. We have now developed a real-time PCR assay
      for rapid, sensitive and quantitative detection of OsHV-1, and compared it with a
      conventional PCR technique described previously. The new assay utilised SYBR((R))
      Green chemistry with specific primers C(9)/C(10) targeting the C region. The melt
      curve analysis of OsHV-1 DNA or DNA extracted from infected material showed only
      one melting temperature peak (75.75+/-0.1 degrees C). The assay had a detection
      limit of 4 copies/microL of viral genomic DNA and a dynamic range of 5 logs.
      Using infected oyster samples as template, the assay was about 100-fold more
      sensitive than single PCR method using C(2)/C(6) primers. The assay was applied
      successfully for rapid diagnosis (100 min) and quantitation of OsHV-1 in
      different developmental stages of Crassostrea gigas. Although it already exists a
      competitive PCR method to quantify OsHV-1 DNA, quantitative data that will emerge
      in future using the new sensitive and reliable assay will illuminate aspects of
      pathogenesis, in particular the viral loads in asymptomatic oysters and the
      kinetics of infection in specific target tissues.

PMID- 18342378
TI  - Wheel-running in a transgenic mouse model of Alzheimer's disease: protection or
      symptom?
AB  - Several studies on both humans and animals reveal benefits of physical exercise
      on brain function and health. A previous study on TgCRND8 mice, a transgenic
      model of Alzheimer's disease, reported beneficial effects of premorbid onset of
      long-term access to a running wheel on spatial learning and plaque deposition.
      Our study investigated the effects of access to a running wheel after the onset
      of Abeta pathology on behavioural, endocrinological, and neuropathological
      parameters. From day 80 of age, the time when Abeta deposition becomes apparent,
      TgCRND8 and wildtype mice were kept with or without running wheel. Home cage
      behaviour was analysed and cognitive abilities regarding object recognition
      memory and spatial learning in the Barnes maze were assessed. Our results show
      that, in comparison to Wt mice, Tg mice were characterised by impaired object
      recognition memory and spatial learning, increased glucocorticoid levels,
      hyperactivity in the home cage and high levels of stereotypic behaviour. Access
      to a running wheel had no effects on cognitive or neuropathological parameters,
      but reduced the amount of stereotypic behaviour in transgenics significantly.
      Furthermore, wheel-running was inversely correlated with stereotypic behaviour,
      suggesting that wheel-running may have stereotypic qualities. In addition, wheel
      running positively correlated with plaque burden. Thus, in a phase when plaques
      are already present in the brain, it may be symptomatic of brain pathology,
      rather than protective. Whether or not access to a running wheel has beneficial
      effects on Alzheimer-like pathology and symptoms may therefore strongly depend on
      the exact time when the wheel is provided during development of the disease.

PMID- 18342379
TI  - Acquisition and retention of enhanced active avoidance are unaffected by
      interference with serotonergic activity.
AB  - Pre-training administration of p-chloroamphetamine (PCA) produces reliable
      deficits of avoidance learning. When animals are trained in inhibitory avoidance
      with relatively high foot-shock intensities, other amnesic treatments have no
      effect. The present experiment was conducted to determine if this protective
      effect of high foot shock is also observed after administration of PCA (10mg/kg,
      i.p., injected 7 days before training; this dose produces a lesion of central
      serotonin neurons). Rats were trained in active avoidance (a single 20-trial
      session), administering shocks of 0.6, 0.8, 1.0, or 1.4 mA to independent groups
      of rats. When compared to saline-injected groups trained with the same
      intensities, PCA produced a significant learning deficit in the low foot-shock
      groups, but not in the high foot-shock animals. These results indicate that the
      dose of PCA administered, which is known to deplete cerebral serotonin, does not
      interfere with acquisition and retention of enhanced active avoidance training.

PMID- 18342380
TI  - Quantitative assessment of the likelihood of the introduction of classical swine
      fever virus into the Danish swine population.
AB  - Classical swine fever virus (CSFV) is a major infectious-disease agent of
      livestock and causes production losses through increased morbidity and mortality,
      particularly of young pigs. We identified the pathways for introduction of CSFV
      into Denmark and assessed the annual probability of introduction (based on a US
      Department of Agriculture model). We developed pathways based on material from
      scientific articles, reports from veterinary agencies and custom officers, and
      consultations with experts in the field. Returning livestock trucks and legal
      meat imports were the most important pathways for CSFV introduction to Denmark
      from other EU states with predicted overall likelihood of one or more
      introductions of CSFV within a median of 130 years (46-280) provided mitigating
      steps, such as cleaning trucks, were maintained to a very high standard. The
      likelihood would increase dramatically if these activities were abandoned: one or
      more introductions within a median of 5.2 years (2-14). The predicted risks from
      live-animal imports and semen were extremely low given the very few imports of
      these products. The most important countries for Denmark's CSFV risk are Germany
      and the Netherlands, though this risk is again predicted to be dramatically
      reduced as long as mitigating activities are maintained. We predicted the risk
      from illegal movements of pork into Denmark to be low because little pork enters
      through this route and only a small fraction of this pork would be fed to pigs.

PMID- 18342381
TI  - A phase I-B trial of the radiosensitizer: etanidazole (SR-2508) with radiosurgery
      for the treatment of recurrent previously irradiated primary brain tumors or
      brain metastases (RTOG Study 95-02).
AB  - RTOG 95-02 assessed patient tolerance to hypoxic cell radiosensitizer,
      etanidazole (SR-2508), combined with radiosurgery. Patients had primary or
      metastatic brain tumors and previously localized or whole brain irradiation. The
      toxicity is reported in three groups of patients according to the tumor size.
      Etanidazole doses of 12g/m2 combined with radiosurgery were well tolerated.

PMID- 18342382
TI  - Bounded stability of the quiet standing posture: an intermittent control model.
AB  - The paper presents a control model of body sway in quiet standing, which aims at
      achieving bounded stability by means of an intermittent control mechanism.
      Control bursts are generated when the current state vector exits an area of
      uncertainty around the reference point in the phase plane. This area is
      determined by the limited resolution of proprioceptive signals and the burst
      generation mechanism is predictive in the sense that it incorporates a rough, but
      working knowledge (internal model) of the biomechanics of the human inverted
      pendulum. We show that such a model, in spite of its simplicity and of the fact
      that it relies on very noisy measurements, is robust and can explain in a
      detailed way the measured sway patterns.

PMID- 18342383
TI  - Targeting green fluorescent protein to dendritic membrane in central neurons.
AB  - Dendritic and axonal processes are input and output sites, respectively, of
      neuronal information, and detailed visualization of these processes may be
      indispensable for elucidating the neuronal circuits and revealing the principles
      of neuronal functions. To establish a method for completely visualizing dendritic
      processes, we first developed green fluorescent protein (GFP)-based proteins and,
      by using lentivirus with a neuron-specific promoter, examined whether or not the
      protein fully visualized the dendritic processes of infected neurons. When GFP
      with a palmitoylation (palGFP) or myristoylation/palmitoylation site (myrGFP) was
      expressed in rat brain with lentiviruses, myrGFP labeled dendritic membrane
      better than palGFP. Subsequently, dendrite-targeting efficiencies of three
      basolateral membrane-sorting and three putative dendrite-targeting domains, which
      were attached to myrGFP C-terminus, were examined in striatonigral GABAergic and
      corticothalamic glutamatergic neurons, and in cultured cortical neurons. Of the
      six domains, C-terminal cytoplasmic domain of low density lipoprotein receptor
      (LDLRct) was most efficient in targeting the protein to dendrites, showing 8.5-15
      fold higher efficiency in striatonigral neurons compared with myrGFP. Finally,
      dendritic membrane-targeting potency of myrGFP-LDLRct was confirmed in transgenic
      mice using Thy1 or Gad1 expression cassette. Thus, myrGFP-LDLRct is an excellent
      synthetic protein for dendritic visualization, and may be a useful tool for the
      morphological analysis of neuronal circuits.

PMID- 18342384
TI  - [French Society of Physical and Rehabilitation Medicine (SOFMER) web site].

PMID- 18342385
TI  - Relationship between response of gamma-glutamyltransferase to alcohol consumption
      and levels of fasting plasma glucose.
AB  - To examine whether the response of fasting plasma glucose (FPG) to alcohol
      consumption differs among individuals, a cross-sectional study was conducted in
      6100 men with a body-mass index below 24 who did not take medication for
      diabetes. Information regarding current medication and lifestyle habits was
      obtained by a self-reported questionnaire. The subjects were divided into four
      groups according to their level of alcohol consumption: non-drinkers, light
      drinkers (1-188ml/week), intermediate drinkers (189-377ml/week), and heavy
      drinkers (>or=378ml/week). The frequency of subjects with an FPG of 110mg/dl or
      more rose significantly as alcohol consumption increased, from 6.7% in non
      drinkers to 10.1% in intermediate drinkers and 12.1% in heavy drinkers. In
      contrast, when only the subjects with a gamma-glutamyltransferase level of less
      than 40IU/L were analyzed, no difference was observed in the frequency of
      subjects with an FPG level of 110mg/dl or more among the four groups. Multiple
      logistic regression analysis also revealed similar results. The findings
      suggested individual variability in the response of FPG to drinking. Appropriate
      levels of drinking could be different among individuals.

PMID- 18342386
TI  - Factors influencing risk of macrosomia in women with gestational diabetes
      mellitus undergoing intensive diabetic care.
AB  - AIMS: The aim of study was to assess the impact of intensive diabetic care,
      defined as target values for fasting glucose of 60-90mg/dl and 1-h postprandial
      glucose of below 130mg/dl, on neonatal birth weight in relation to risk
      indicators for fetal macrosomia in women with gestational diabetes mellitus
      (GDM). METHODS: In women with (N=543) and without GDM (N=1011) age, height,
      weight, previous GDM, history of macrosomia, family history of type 2 diabetes,
      parity and weight gain during pregnancy were recorded. RESULTS: Neonatal birth
      weight and frequency distribution of macrosomia and infants with small for
      gestational age did not differ between women with and without GDM. Neonatal birth
      weight was strongly associated with traditional risk predictors for GDM, such
      like prior macrosomia (OR 5.03; 95%CI 3.36-7.53), prior GDM (OR 2.52; 95%CI 1.37
      4.64) and prepregnancy body mass index (BMI)>23kg/m(2) (OR 1.82; 95%CI 1.27
      2.63). CONCLUSIONS: Neonatal birth weight and the incidence of macrosomia were
      similar in comparison of pregnancies with and without GDM. In the population of
      Caucasian women the strongest single predictors for macrosomia were prior
      macrosomia, BMI>23kg/m(2) and prior GDM.

PMID- 18342387
TI  - Anti-thyroid peroxidase antibody, IA-2 antibody, and fasting C-peptide levels
      predict beta cell failure in patients with latent autoimmune diabetes in adults
      (LADA)--a 5-year follow-up of the Ehime study.
AB  - OBJECTIVE: To clarify the natural course and factors involved in beta cell
      failure in Japanese latent autoimmune diabetes in adults (LADA) patients.
      RESEARCH DESIGN AND METHODS: Insulin secretion in 57 LADA patients identified
      from among 4980 adult-onset diabetic patients in a hospital-based Ehime study
      were examined over a 5-year period. Postprandial serum C-peptide levels below
      0.33 nmol/l were defined as beta cell failure. The involvement of clinical and
      immunological factors in the progression to beta cell failure were evaluated.
      RESULTS: Forty-two of the fifty-seven LADA patients completed the 5-year follow
      up. Eleven (26.2%) required insulin treatment and five (11.9%) progressed to beta
      cell failure. A Cox regression analysis revealed that positive anti-thyroid
      peroxidase antibody (TPOAb) and insulinoma-associated protein 2 (IA-2Ab) were
      associated with the need for insulin treatment (p<0.05 and p<0.01, respectively).
      Positive TPOAb, anti-thyroglobulin antibody (TGAb), IA-2 antibody (p<0.01 for
      each), and lower serum fasting C-peptide levels (p<0.05) were contributors to the
      progression to beta cell failure. Involvement of type 1 diabetes susceptible HLA
      class II genes was not evident. CONCLUSIONS: Japanese LADA patients are a
      heterogeneous population. In addition to IA-2 antibody, presence of TPOAb and
      fasting C-peptide level could indicate an oncoming deterioration of beta cell
      function.

PMID- 18342388
TI  - Allocating HIV prevention resources: a tool for state and local decision making.
AB  - The CDC provides funding for HIV prevention activities and state and local
      decision-makers must allocate these funds. The implementation of a resource
      allocation tool designed to facilitate this process that incorporates concepts of
      efficiency and equity as well as CDC mandates on the use of community planning
      groups is demonstrated, showing how information obtained from the resource
      allocation tool can be used to guide the policy analysis. The demonstration uses
      a simplified example based on data from Florida. The tool quantifies the inherent
      trade-offs associated with efficiency and equity and allows decision-makers to
      explore different ways of achieving equity. Given the underlying epidemiological
      model, results are not necessarily linear so common proportionality assumptions
      do not hold. However, a sense of equity can be provided by implementing various
      metrics allowing the policy maker flexibility in their decision process. By
      quantifying the impact of policy choices in terms of efficiency, cost, and
      distribution, the resource allocation tool makes the decision process more
      transparent and permits more informed choices.

PMID- 18342389
TI  - Present situation of vector-control management in Bangladesh: a wake up call.
AB  - OBJECTIVES: Kala-azar or visceral leishmaniasis is one of the major vector-borne
      diseases in Bangladesh. The disease is transmitted by sandfly. The incidence of
      the disease, which has been increasing since the early eighties, must be reduced
      by taking adequate vector-control measures. The objective of the present study
      was to identify the favorable factors and the constraints of present vector
      control management in Bangladesh. METHODS: Purposively selected senior
      entomologist and retired senior entomologist at central level, civil surgeons,
      entotechnicians, health inspectors and spray men from kala-azar-endemic
      districts, community leaders, and NGO representatives were key informants of the
      study. A household survey to learn about knowledge and perceptions of the people
      about kala-azar vector was carried out, using a structured questionnaire, in 202
      randomly selected households. RESULTS: Practically, there was no vector-control
      activity in the nine most kala-azar-endemic districts of Bangladesh. Inadequate
      human resources, lack of logistics, and unavailability of funds for vector
      control were the major constraints. Community perception about kala-azar vector
      was poor. However, the use of bednets in the community was high. No private
      organization was involved in kala-azar vector control. Knowledge of the spray men
      about the insecticide-spraying technique was also unsatisfactory. CONCLUSION:
      Kala-azar vector control in Bangladesh needs immediate attention of policy-makers
      and donors, otherwise, elimination of kala-azar from the country by 2015 may not
      be achievable.

PMID- 18342390
TI  - HDL-cholesterol and the incidence of lung cancer in the Atherosclerosis Risk in
      Communities (ARIC) study.
AB  - SUMMARY: This study examined prospectively the association of baseline plasma HDL
      cholesterol levels with incidence of lung cancer in 14,547 members of the
      Atherosclerosis Risk in Communities (ARIC) cohort. There were 259 cases of
      incident lung cancer identified during follow-up from 1987 through 2000. Results
      of this study indicated a relatively weak inverse association of HDL-cholesterol
      with lung cancer that was dependent on smoking status. The hazard ratio of lung
      cancer incidence in relation to low HDL-cholesterol, adjusted for race, gender,
      exercise, alcohol consumption, body mass index, triglycerides, age, and cigarette
      pack-years of smoking, was 1.45 (95% confidence interval 1.10, 1.92). This
      association was observed among former smokers (hazard ratio: 1.77, 95% confidence
      interval 1.05, 2.97), but not current smokers. The number of cases among never
      smokers in this study was too small (n=13) for meaningful interpretation of
      effect estimates. Excluding cases occurring within 5 years of baseline did not
      appreciably change the point estimates, suggesting lack of reverse causality. The
      modest association of low plasma HDL-cholesterol with greater incident lung
      cancer observed in this study is in agreement with existing case-control studies.

PMID- 18342391
TI  - The significance of leptin, adiponectin, and resistin serum levels in non-small
      cell lung cancer (NSCLC).
AB  - SUMMARY: Adipose tissue secretes adipokines with proinflammatory and anti
      inflammatory properties. Our aim was to assess the role of adipose tissue in
      generalized inflammatory state of advanced NSCLC patients and the possible use of
      leptin, adiponectin and resistin as diagnostic and prognostic markers.
      Correlation of adipose tissue with weight loss in advanced NSCLC patients was
      also studied. Fasting serum levels of leptin, adiponectin and resistin were
      determined in 101 advanced NSCLC patients (76 without weight loss and 25 with
      weight loss) and 51 healthy volunteers using commercially available ELISA.
      Adipokine serum levels were determined at diagnosis, at the end of first-line
      chemotherapy and at the time of disease progression for those who responded to
      treatment. Epidemiological, anthropometrical and laboratory data were assessed.
      Serum leptin and adiponectin levels presented no differences. Serum resistin
      levels were significantly increased in NSCLC patients after adjustment for age,
      sex and BMI. Multivariate analysis showed that these adipokines at diagnosis
      could not be used as predictive factors for overall survival or time to
      progression. Only serum resistin levels were associated with weight loss. Despite
      no direct involvement of leptin and adiponectin, resistin as a proinflammatory
      cytokine may play a role in the pathogenesis of weight loss in NSCLC patients.

PMID- 18342392
TI  - Protein tyrosine phosphatases in osteoclast differentiation, adhesion, and bone
      resorption.
AB  - Osteoclasts are large cells derived from the monocyte-macrophage hematopoietic
      cell lineage. Their primary function is to degrade bone in various physiological
      contexts. Osteoclasts adhere to bone via podosomes, specialized adhesion
      structures whose structure and subcellular organization are affected by
      mechanical contact of the cell with bone matrix. Ample evidence indicates that
      reversible tyrosine phosphorylation of podosomal proteins plays a major role in
      determining the organization and dynamics of podosomes. Although roles of several
      tyrosine kinases are known in detail in this respect, little is known concerning
      the roles of protein tyrosine phosphatases (PTPs) in regulating osteoclast
      adhesion. Here we summarize available information concerning the known and
      hypothesized roles of the best-researched PTPs in osteoclasts - PTPRO, PTP
      epsilon, SHP-1, and PTP-PEST. Of these, PTPRO, PTP epsilon, and PTP-PEST appear
      to support osteoclast activity while SHP-1 inhibits it. Additional studies are
      required to provide full molecular details of the roles of these PTPs in
      regulating osteoclast adhesion, and to uncover additional PTPs that participate
      in this process.

PMID- 18342393
TI  - A new role for cortactin in invadopodia: regulation of protease secretion.
AB  - Invadopodia are actin-dependent organelles that function in the invasion and
      remodeling of the extracellular matrix (ECM) by tumor cells. Cortactin, a
      regulator of the Arp2/3 complex, is of particular importance in invadopodia
      function. While most of the focus has been on the possible role of cortactin in
      actin assembly for direct formation of actin-rich invadopodia puncta, our recent
      data suggest that the primary role of cortactin in invadopodia is to promote
      protease secretion. In this manuscript, we review our previous work and present
      new data showing that cortactin is essential for both the localization of key
      invadopodia matrix metalloproteinases (MMPs) to actin-positive puncta at the cell
      ECM interface and for ECM degradation induced by overexpression of MT1-MMP-GFP.
      Based on these data and results from the literature, we propose potential
      mechanisms by which cortactin may link vesicular trafficking and dynamic branched
      actin assembly to regulate protease secretion for invadopodia-associated ECM
      degradation.

PMID- 18342394
TI  - The role of palladin in actin organization and cell motility.
AB  - Palladin is a widely expressed protein found in stress fibers, focal adhesions,
      growth cones, Z-discs, and other actin-based subcellular structures. It belongs
      to a small gene family that includes the Z-disc proteins myopalladin and
      myotilin, all of which share similar Ig-like domains. Recent advances have shown
      that palladin shares with myotilin the ability to bind directly to F-actin, and
      to crosslink actin filaments into bundles, in vitro. Studies in a variety of
      cultured cells suggest that the actin-organizing activity of palladin plays a
      central role in promoting cell motility. Correlative evidence also supports this
      hypothesis, as palladin levels are typically up-regulated in cells that are
      actively migrating: in developing vertebrate embryos, in cells along a wound
      edge, and in metastatic cancer cells. Recently, a mutation in the human palladin
      gene was implicated in an unusually penetrant form of inherited pancreatic
      cancer, which has stimulated new ideas about the role of palladin in invasive
      cancer.

PMID- 18342395
TI  - Effect of sensory education on willingness to taste novel food in children.
AB  - As part of 'EduSens', a project aiming to measure the effect of a sensory
      education program developed in France on the food behaviour of school children,
      the present paper shows the results regarding neophobia. One hundred and eighty
      children (8-10 years old) were involved in the study. Half of them (experimental
      group) were educated during school-time with the 12 sessions of taste lessons
      "Les classes du gout" by J. Puisais. The others served as a control group. Food
      neophobia was evaluated before and after the education period of the experimental
      group and once again 10 months later. An adapted food neophobia scale was used
      (AFNS) and the willingness to taste novel food (WTNF) was evaluated by the
      presentation of eight unknown foods. To improve involvement in the expressed
      willingness to taste new foods, the children were told that they would have to
      eat one of the not rejected unknown foods afterwards. Results revealed that, at
      the end of the education period, in the educated group, declarative food
      neophobia decreased significantly and participants' willingness to taste novel
      food seemed to increase compared to the control group. Nevertheless, these
      effects had disappeared 10 months later. Thus, we have shown that sensory
      education can influence childrens' food neophobia, but does so only temporarily.
      This is especially true for the WTNF test, which measures the expression of
      neophobia in concrete situations, whereas neophobia measured as a psychological
      trait by the AFNS test hardly changes.

PMID- 18342396
TI  - Associations between maternal feeding style and food intake of children with a
      higher risk for overweight.
AB  - OBJECTIVE: The aim of this study is to examine the impact of different feeding
      strategies on the child's food intake as well as the effect and influence socio
      economic status and weight have on the use of feeding strategies. METHODS: 219
      mothers and their children between 3 and 6 years of age at risk for becoming
      overweight took part in this cross-sectional study. The participating mothers
      were recruited from inpatient-clinics and kindergartens with a lower socio
      economic background. Besides demographic and weight data, which describe the
      child's risk for overweight, the mothers were asked for their use of feeding
      strategies and their child's food intake. RESULTS: Maternal feeding practices
      have an important impact (22.2-26.9% explained variance) on the child's food
      intake. There are three strategies (rewarding, child's control and pressure)
      which turned out to be significant predictors. Additionally, the child's weight,
      family income and educational level have an effect on the choice of feeding
      strategies and their impact on the child's food intake. CONCLUSIONS: The results
      are evidence of the influence of parental feeding practices on the child's food
      intake. Parent training in prevention and intervention of childhood obesity
      should include the discussion and modification of feeding practices.

PMID- 18342397
TI  - Mirror exposure reduces body dissatisfaction and anxiety in obese adolescents: a
      pilot study.
AB  - Many obese adolescents show intense body shape and weight concerns that render
      them vulnerable to cognitive biases, psychological distress and eating disorders.
      Current treatments, however, generally do not address negative body image in
      obese adolescents. The present pilot study tested if body exposure and describing
      one's body in a neutral way is an effective approach for increasing body
      satisfaction in obese adolescents. The exposure was shown to be a powerful
      strategy to decrease anxiety and to increase body satisfaction. Also body weight
      at post-treatment was a significant predictor of positive feelings. These results
      indicate that adding body exposure and neutral description of one's body to a
      weight reduction programme might be an effective way to increase body
      satisfaction in obese adolescents.

PMID- 18342398
TI  - Effects of L-phenylalanine on energy intake in overweight and obese women:
      interactions with dietary restraint status.
AB  - L-Phenylalanine (Phe), is a potent releaser of the satiety hormone,
      cholecystokinin (CCK) and previous studies, conducted primarily in men, show that
      ingestion of Phe reduces energy intake. The objective of the current study was to
      test the effects of Phe on energy intake in overweight and obese women. Subjects
      (n=32) received three treatments (high-dose (10 g Phe), low-dose (5 g Phe and 5 g
      glucose) or control (10 g glucose)) 20 min before an ad libitum lunch and dinner
      meal in a within-subjects', counterbalanced, double-blind study. No effect of Phe
      was found, however, interactions with dietary restraint status were detected in
      post-hoc analyses. Energy intake over the day was 11% lower following high-dose
      Phe versus control for women classified in the lower tertile of rigid restraint,
      a subscale of the dietary restraint scale, whereas no effects were noted for
      women in the middle and upper tertiles. High-dose Phe increased ratings of
      nausea, however, reduced energy intake in the high-dose condition was noted only
      for subjects with low nausea ratings. These results suggest that the satiety
      response to Phe is modulated by rigid restraint status and that reductions in
      food intake occur independently of Phe's effects on nausea.

PMID- 18342399
TI  - Bovine hemoglobin: an attractive source of antibacterial peptides.
AB  - A peptic hemoglobin hydrolysate was fractioned by a semi-preparative reversed
      phase HPLC and some fractions have an antibacterial activity against four
      bacteria strains: Micrococcus luteus A270, Listeria innocua, Escherichia coli and
      Salmonella enteritidis. These fractions were analyzed by ESI/MS and ESI/MS/MS, in
      order to characterize the peptides in these fractions. Each fraction contains at
      least three peptides and some fractions contain five peptides. All these
      fractions were purified several times by HPLC to obtain pure peptides. Thirty
      antibacterial peptides were identified. From the isolated antibacterial peptides,
      24 peptides were derived from the alpha chains of hemoglobin and 6 peptides were
      derived from the beta chains of hemoglobin. The lowest concentration of these
      peptides (minimum inhibitory concentration (MIC)) necessary to completely inhibit
      the growth of four bacteria strain was determined. The cell population of all of
      the tested bacteria species decreased by at least 97% after a 24-h incubation
      with any of the peptides at the minimum inhibitory concentration.

PMID- 18342400
TI  - Peripheral obestatin has no effect on feeding behavior and brain Fos expression
      in rodents.
AB  - Obestatin is produced in the stomach from proghrelin by post-translational
      cleavage. The initial report claimed anorexigenic effects of obestatin in mice.
      Contrasting studies indicated no effect of obestatin on food intake (FI). We
      investigated influences of metabolic state (fed/fasted), environmental factors
      (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in
      rats, and used the protocol from the original study assessing obestatin effects
      in mice. FI was determined in male rats injected ip before onset of dark or light
      phase, with obestatin (1 or 5 micromol/kg), CCK8S (3.5 nmol/kg) or 0.15 M NaCl,
      after fasting (16 h, n=8/group) or ad libitum (n=10-14/group) food intake. Fos
      expression in hypothalamic and brainstem nuclei was examined in freely fed rats
      90 min after obestatin (5 micromol/kg), CCK8S (1.75 nmol/kg) or 0.15 M NaCl
      (n=4/group). Additionally, fasted mice were injected ip with obestatin (1
      micromol/kg) or urocortin 1 (2 nmol/kg) 15 min before food presentation. No
      effect on FI was observed after obestatin administration during the light and
      dark phase under both metabolic conditions while CCK8S reduced FI irrespectively
      of the conditions. The number of Fos positive neurons was not modified by
      obestatin while CCK8S increased Fos expression in selective brain nuclei.
      Obestatin did not influence the refeeding response to a fast in mice, while
      urocortin was effective. Therefore, peripheral obestatin has no effect on FI
      under various experimental conditions and did not induce Fos in relevant central
      neuronal circuitries modulating feeding in rodents.

PMID- 18342401
TI  - Constrained analogues of tocainide as potent skeletal muscle sodium channel
      blockers towards the development of antimyotonic agents.
AB  - 1-Benzyl-N-(2,6-dimethylphenyl)piperidine-3-carboxamide and 4-benzyl-N-(2,6
      dimethylphenyl)piperazine-2-carboxamide, two conformationally restricted
      analogues of tocainide, were designed and synthesized as voltage-gated skeletal
      muscle sodium channel blockers. They showed, with respect to tocainide, a marked
      increase in both potency and use-dependent block.

PMID- 18342402
TI  - Synthesis, biological evaluation and docking studies of 4-amino substituted 1H
      pyrazolo[3,4-d]pyrimidines.
AB  - The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with
      their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is
      reported. Some compounds emerged as good dual inhibitors of the two enzymes,
      showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K
      562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking
      studies have been also performed to analyze the binding mode of compounds under
      study and to identify the structural determinants of their interaction with both
      Src and Abl.

PMID- 18342403
TI  - Rational design, synthesis and biological evaluation of new 1,5-diarylpyrazole
      derivatives as CB1 receptor antagonists, structurally related to rimonabant.
AB  - Among cannabinoid type-1 (CB(1)) receptor antagonists, those developed around the
      1,5-diarylpyrazole scaffold of rimonabant (Acomplia are the most extensively
      investigated. In recent years, many SAR and QSAR reports on this topic have been
      published, focusing on the substitution and orientation of the N1 and C5 aryl
      functionalities and on the substituents at the 3-carboxamide position. In this
      context, the purpose of our study was to design and synthesize a set of 1-(2,4
      dichlorophenyl)-5-arylpyrazoles strictly related to rimonabant, but with the
      hydrazide/amide group shifted from position 3 to position 4 of the pyrazole
      scaffold. The synthesized compounds were evaluated in vitro for their affinity on
      human CB(1) and CB(2) (cannabinoid type-2) receptors. Computational studies,
      performed both in the design step and after biological assays, contributed to
      rationalize the obtained results in terms of specific molecular interactions
      between antagonists and the human CB(1) receptor.

PMID- 18342404
TI  - Structure-activity relationships in the acronycine and benzo[b]acronycine series:
      role of the pyran ring.
AB  - In order to explore the structure-activity relationships in the acronycine
      series, simplified analogues of cis-1,2-diacetoxy-1,2-dihydroacronycine and cis
      1,2-diacetoxy-1,2-dihydrobenzo[b]acronycine (S23906-1, under clinical trials)
      lacking the fused pyran ring, but possessing an acetoxymethyl leaving group at
      position 4 were prepared. These new analogues only displayed marginal
      antiproliferative activity compared to the parent compounds. The presence of the
      angularly fused dimethylpyran ring appears as an indispensable structural
      requirement to observe significant cytotoxic activity in this series.

PMID- 18342405
TI  - In vitro and in vivo investigations on the antiviral activity of a series of
      mixed-valence rare earth borotungstate heteropoly blues.
AB  - A series of mixed-valence rare earth borotungsto-heteropoly blues,
      K15H2[Ln(BW9W2O39)2].28H2O (Ln2, Ln=La, Ce, Pr, Nd, Sm, Eu, Gd), have been
      prepared and characterized by IR, UV, XPS, ESR and electrochemistry. The
      cytotoxicity and antiviral activity of these rare earth borotungstate heteropoly
      blues were investigated against influenza A(FluVA) strain (A/H1N1/Jingfang/1/91
      and A/H3N2/Jingfang/30/95) and influenza virus B(FluVB) (B/Hufang/1/87) in MDCK
      cells. The results show that K15H2[Pr(BW9W2O39)2].28H2O (Pr2) exhibits the
      highest antiviral activity against FluVA with EC50 of less than 4.0 microg/ml
      (A/H1N1/Jingfang/1/91) and 6.0 microg/ml (A/H3N2/Jingfang/30/95), respectively,
      and has the lowest toxicity with CC50 of more than 480 microg/ml against MDCK
      cells. Additionally, both K15H2[Pr(BW9W2O39)2].28H2O (Pr2) and
      K15H2[Eu(BW9W2O39)2].28H2O (Eu2) showed excellent antiviral activities against
      FluVB by inhibiting FluVB replication at an EC50 of less than 8.0 microg/ml.
      Furthermore, investigation on in vivo antiviral activity of Pr2 against
      FluVA(FM1) in mice by giving the dosage either orally (p.o.) or intraperitoneally
      (i.p.), indicates that Pr2 exhibits higher inhibitory activity than that of
      positive control, virazole, and that it's more effective when administered by
      i.p.

PMID- 18342406
TI  - Dietary and nutritional biomarkers of lens degeneration, oxidative stress and
      micronutrient inadequacies in Indian cataract patients.
AB  - BACKGROUND & AIMS: Habitual food and nutrient intakes of 140 Indian cataract
      patients and 100 age- and sex-matched controls (50-75 years), from high income
      group and low income groups, were assessed. METHODS: Food intake was recorded by
      food frequency questionnaire and data were examined for linkages with blood/lens
      parameters of oxidative stress through a case-control study. RESULTS: Intake of
      animal foods and fried snacks was significantly higher while vegetables, green
      leafy vegetables, fruit, tea and micronutrient intakes were lower in patients
      than in controls (p<0.001). Lens oxidative stress and opacity showed a
      significant negative association with fruit intake (p<0.05). Multiple regression
      analysis indicated association of intakes of iron, beta-carotene, ascorbic acid,
      tannic acid and inositol pentaphosphate with plasma oxidative stress (p<0.01) and
      association of intakes of iron, ascorbic acid and inositol triphosphate with lens
      oxidative stress (p<0.01). Weighted least square regression for lens opacity
      revealed that intakes of ascorbic acid, folic acid and inositol pentaphosphate
      explained 59.7% of the total variation (p<0.01). CONCLUSIONS: Dietary deficiency
      of antioxidant micronutrients was greater for patients than controls. Deficiency
      of beta-carotene, ascorbic acid, folic acid, iron, phytate and polyphenols
      increased oxidative stress in blood and lens.

PMID- 18342407
TI  - Amino acids are necessary for the insulin-induced activation of mTOR/S6K1
      signaling and protein synthesis in healthy and insulin resistant human skeletal
      muscle.
AB  - BACKGROUND: Amino acids (AA) activate the mammalian target of rapamycin (mTOR)
      signaling pathway but overactivation has a negative feedback effect on insulin
      signaling which may lead to insulin resistance and type 2 diabetes (T2DM).
      PURPOSE: To determine the effect of reduced AA concentrations on mTOR and insulin
      signaling during increased nutrient and insulin availability. METHODS: Six
      control and six T2DM subjects were studied at baseline and following a 5h AA
      lowering high energy and insulin clamp. Stable isotopic techniques in combination
      with femoral catheterizations were used to measure AA kinetics across the leg
      while muscle biopsies were used to measure mTOR and insulin signaling proteins
      using immunoblotting techniques. RESULTS: AA concentrations decreased by
      approximately 30-60% in both groups (p<0.05). Phospho-mTOR, S6K1, eEF2, and
      eIF2alpha were unchanged in both groups following the clamp (p>0.05). In T2DM
      subjects, IRS-1 serine phosphorylation was unchanged while phospho-AMPKalpha
      decreased and phospho-Akt, phospho-AS160 and glucose uptake increased following
      the clamp (p<0.05). In comparison, AA concentrations were maintained in a
      separate group during an insulin infusion. In this group, phospho-Akt, mTOR and
      S6K1 (n=4) increased. CONCLUSION: Amino acids are necessary for insulin-induced
      activation of mTOR signaling and protein synthesis in both healthy and insulin
      resistant skeletal muscle.

PMID- 18342409
TI  - Chimeric foot-and-mouth disease viruses: evaluation of their efficacy as
      potential marker vaccines in cattle.
AB  - Previous work in pigs, has demonstrated that full protection against foot-and
      mouth disease (FMD) can be achieved following vaccination with chimeric foot-and
      mouth disease virus (FMDV) vaccines, in which the VP1 G-H loop had been
      substituted with that from another serotype. If proven to be effective in other
      economically important species such as cattle, such vaccine constructs could be
      trialed as potential marker vaccines. Here, we determine if G-H loop chimera FMDV
      vaccines can: (i) protect cattle from virus challenge and (ii) induce an antibody
      response that would enable the identification of infection, regardless of
      vaccination status. Inactivated, oil adjuvanated, chimeric vaccine constructs,
      based on the backbone sequence of the A(12)119 serotype virus, fully protected
      cattle from challenge 21 days post-vaccination. Differentiation assays developed
      for use in this study were able to identify sub-clinical infection, which in one
      vaccinated animal, persisted beyond day 32 post-challenge. This paper emphasises
      the importance of epitopes outside of the VP1 G-H loop for protective immunity in
      cattle, and demonstrates that chimeric FMDV vaccines could prove to be useful
      marker vaccines for the future.

PMID- 18342408
TI  - Prime-boost immunization with cruzipain co-administered with MALP-2 triggers a
      protective immune response able to decrease parasite burden and tissue injury in
      an experimental Trypanosoma cruzi infection model.
AB  - Cruzipain (Cz), a key Trypanosoma cruzi enzyme, is a main candidate antigen for
      vaccines against Chagas' disease. We evaluated a vaccination protocol based on
      intradermal priming with recombinant Cz and intranasal boosting with rCz co
      administered with a derivative of the TLR2/6 agonist MALP-2. Vaccination
      triggered strong systemic and mucosal antibody responses, and a vigorous cell
      mediated immunity characterized by lymphoproliferation, DTH reactivity and IFN
      gamma production. The immune responses protected against a lethal trypomastigote
      challenge and, upon sub-lethal infection, immunized mice showed reduction of
      tissue damage and normal enzymatic markers of muscle injury. This prime-boost
      regimen appears promising for further development, since warranted survival,
      provided efficient control of parasite load and restricted inflammatory myopathy.

PMID- 18342410
TI  - Identification and characterization of novel antigenic vaccine candidates of
      Actinobacillus pleuropneumoniae.
AB  - Actinobacillus pleuropneumoniae is an important respiratory pathogen of swine,
      for which there is no highly effective vaccine. A phage expression library of the
      A. pleuropneumoniae genome was constructed and screened to identify potential
      vaccine components. Open reading frames within immuno-reactive phage were
      analyzed in silico to identify conserved outer membrane proteins. Four ORFs,
      named comL, lolB, lppC and ompA were chosen for further study. The four encoded
      proteins were shown experimentally to be antigenic, highly conserved, outer
      membrane, in vivo-expressed proteins. In pig protection studies, none of the
      proteins was individually capable of protecting pigs from colonization and
      infection with the homologous A. pleuropneumoniae strain, despite a detectable
      specific antibody response being induced.

PMID- 18342411
TI  - Intranasal delivery of DNA encoding antigens of Mycobacterium tuberculosis by non
      pathogenic invasive Escherichia coli.
AB  - Naturally invasive bacteria have been successfully used for mucosal delivery of
      DNA vaccines against bacterial, viral and tumour antigens. Recently, an
      alternative delivery system based on a genetically modified mutant of the non
      pathogenic commensal bacterium Escherichia coli, was developed and successfully
      used to deliver therapeutic genes and immunogenic proteins to epithelial cells in
      vivo. In this work, we used these recombinant invasive bacteria to deliver DNA
      vaccines against two Mycobacterium tuberculosis proteins (FbpA, and HtpX)
      following intranasal administration. Both DNA vaccines were able to induce an
      antigen-specific T-cell response. Moreover, mice immunized with the recombinant
      bacteria carrying the DNA vaccine encoding HtpX, were significatively protected
      from challenge with M. tuberculosis.

PMID- 18342412
TI  - Stakeholder interaction within the ERICA Integrated Approach.
AB  - Within the ERICA project, stakeholder involvement has been addressed within three
      main areas: generic interactions throughout the project, specific consultation by
      means of attendance to events and considerations as part of the ERICA Integrated
      Approach and Assessment Tool. The word stakeholders meant namely any individual
      or group who may be affected by or have an interest in an issue, and to include
      experts, lay-people and the public. An End-Users-Group (EUG) was set up to
      facilitate the two-way dialogue between the ERICA Consortium and stakeholders.
      The ERICA EUG consisted of representatives of 60 organisations ranging from
      regulatory bodies, national advisory bodies, academia, non-governmental
      organisations, industry, consultants and inter-governmental organisations.
      Stakeholder interaction was included from the very start of the project. Inputs
      from the EUG were recorded and in most instances incorporated within the
      development of the project and thus influenced and helped to shape some of the
      ERICA deliverables.

PMID- 18342413
TI  - Seasonal variation of air kerma rate in Sicily.
AB  - Thermoluminescence dosimetry has been used to measure air kerma in 29 sites in
      Sicily. Four three month measurement campaigns have been carried out in order to
      assess seasonal variations. Average annual values between 20 and 90 nGy h(-1),
      after cosmic background subtraction, are reported. Average annual values are
      strongly dependent on site lithology, and we find that winter data are generally
      the highest, while spring and autumn rates are generally the lowest with very
      similar trends in any site. Summer values generally lay in between. Largest
      seasonal variations are found in sites along the southern coast of the island,
      probably because of stronger action of winds affecting radon, along with its
      progeny, concentrations at ground level.

PMID- 18342414
TI  - An assessment of cumulative external doses from Chernobyl fallout for a forested
      area in Russia using the optically stimulated luminescence from quartz inclusions
      in bricks.
AB  - Optically stimulated luminescence (OSL) has been used for estimation of the
      accumulated doses in quartz inclusions obtained from two fired bricks, extracted
      in July 2004 from a building located in the forested surroundings of the
      recreational area Novie Bobovichi, the Bryansk Region, Russia. The area was
      significantly contaminated by Chernobyl fallout with initial (137)Cs ground
      deposition level of approximately 1.1 MBq m(-2). The accumulated OSL doses in
      sections of the bricks varied from 141 to 207 mGy, of which between 76 and 146
      mGy are attributable to Chernobyl fallout. Using the OSL depth-dose profiles
      obtained from the exposed bricks and the results from a gamma-ray-survey of the
      area, the Chernobyl-related cumulative gamma-ray dose for a point detector
      located in free air at a height of 1m above the ground in the study area was
      estimated to be ca. 240 mGy for the time period starting on 27 April 1986 and
      ending on 31 July 2004. This result is in good agreement with the result of
      deterministic modelling of the cumulative gamma-ray dose in free air above
      undisturbed ground from the Chernobyl source in the Bryansk Region. Over the same
      time period, the external Chernobyl-related dose via forest pathway for the most
      exposed individuals (e.g., forest workers) is estimated to be approximately 39
      mSv. Prognosis for the external exposure from 1986 to 2056 is presented and
      compared with the predictions given by other investigators of the region.

PMID- 18342415
TI  - Joint kinetics during Tai Chi gait and normal walking gait in young and elderly
      Tai Chi Chuan practitioners.
AB  - BACKGROUND: Tai Chi Chuan is becoming a popular exercise among elders. This study
      measured the inter-segmental forces and moments at the lower extremity joints
      during a Tai Chi gait as compared to those during normal walking gait, in both
      apparently healthy young and elderly Tai Chi Chuan practitioners. METHODS: Three
      dimensional inter-segmental joint reaction force and moment were computed using
      the Inverse Dynamic Approach based on the kinematics and ground reaction force
      measurements in a laboratory setting in six young (two females, mean age 28; SD 6
      years) and six elderly (five females, mean age 72; SD 8 years) subjects who had
      previous training of Yang style Tai Chi Chuan. FINDINGS: The results showed
      significant gait differences in both age groups, with significantly smaller peak
      compressive forces, larger peak shear forces in the ankle, knee and hip joints,
      and larger peak moments in the knee and hip joints during Tai Chi gait as
      compared to normal gait. Moreover, the peak shear force was oriented more in the
      medial-lateral direction at the ankle and knee joints, and the peak moment was in
      the frontal plane at the knee and hip joints. The results also showed significant
      age differences, with significantly smaller peak shear forces in all three joints
      in the elderly group than in the young group during Tai Chi gait. INTERPRETATION:
      Tai Chi gait has an increased shear force and frontal plane torque at lower
      extremity joints than normal gait. The shear force at all three lower extremity
      joints during Tai Chi gait is lower in the elderly subjects than young subjects.
      This data suggest that, in Tai Chi Chuan training, elderly people with
      degenerative joint diseases in the lower extremity should use caution when
      practicing Tai Chi Chuan.

PMID- 18342416
TI  - Static and dynamic biomechanical properties of the regenerating rabbit Achilles
      tendon.
AB  - BACKGROUND: Since tendons show viscoelastic behavior, dynamic viscoelastic
      properties should be assessed in addition to static biomechanical properties. We
      evaluated differences between static and dynamic biomechanical properties of the
      regenerating rabbit Achilles tendon following tenotomy. METHODS: At 3, 6, or 12
      weeks after right Achilles tenotomy, the right (regenerating) and left (control)
      tendons were collected with the calcaneus from 49 rabbits. A unidirectional
      failure test and a dynamic viscoelastic test were conducted. FINDINGS: Tensile
      strength and Young's modulus (static biomechanical properties) in the
      regenerating group at Week 6 were significantly greater than at Week 3, while at
      Week 12, these were significantly greater than at Week 6. However, even at Week
      12, both parameters were less than in the control group. The value of tan delta
      represents dynamic viscoelasticity, a smaller tan delta indicates greater
      elasticity. tan delta for the regenerating group was significantly greater than
      for the control group at Week 3, but regenerating and control groups did not
      significantly differ at Week 6. No marked change was seen from Weeks 6 to 12 in
      the regenerating group, and no significant difference in tan delta was evident
      between the regenerating and control groups at Week 12. INTERPRETATION: Dynamic
      biomechanical properties of regenerating rabbit Achilles tendons may improve more
      rapidly than static biomechanical properties. Ability to tolerate dynamic
      movement in the healing Achilles tendon may improve more rapidly than ability to
      withstand static stresses.

PMID- 18342417
TI  - Mercury cycling in surface water, pore water and sediments of Mugu Lagoon, CA,
      USA.
AB  - Mugu Lagoon is an estuary in southern California, listed as impaired for mercury.
      In 2005, we examined mercury cycling at ten sites within at most four habitats.
      In surface water (unfiltered and filtered) and pore water, the concentration of
      total mercury was correlated with methylmercury levels (R2=0.29, 0.26, 0.27,
      respectively, p<0.05), in contrast to sediments, where organic matter and reduced
      iron levels were most correlated with methylmercury content (R2=0.37, 0.26,
      respectively, p<0.05). Interestingly, levels for percent methylmercury of total
      mercury in sediments were higher than typical values for estuarine sediments
      (average 5.4%, range 0.024-38%, n=59), while pore water methylmercury Kd values
      were also high (average 3.1, range 2.0-4.2l kg(-1), n=39), and the estimated
      methylmercury flux from sediments was low (average 1.7, range 0.14-5.3ng m(-2)
      day(-1), n=19). Mercury levels in predatory fish tissue at Mugu are >0.3ppm,
      suggesting biogeochemical controls on methylmercury mobility do not completely
      mitigate methylmercury uptake through the food web.

PMID- 18342418
TI  - Sensitivity analysis of a parameterization of the stomatal component of the DO3SE
      model for Quercus ilex to estimate ozone fluxes.
AB  - A sensitivity analysis of a proposed parameterization of the stomatal conductance
      (g(s)) module of the European ozone deposition model (DO(3)SE) for Quercus ilex
      was performed. The performance of the model was tested against measured g(s) in
      the field at three sites in Spain. The best fit of the model was found for those
      sites, or during those periods, facing no or mild stress conditions, but a worse
      performance was found under severe drought or temperature stress, mostly
      occurring at continental sites. The best performance was obtained when both
      f(phen) and f(SWP) were included. A local parameterization accounting for the
      lower temperatures recorded in winter and the higher water shortage at the
      continental sites resulted in a better performance of the model. The overall
      results indicate that two different parameterizations of the model are needed,
      one for marine-influenced sites and another one for continental sites.

PMID- 18342419
TI  - Interactions of forests with secondary air pollutants: some challenges for future
      research.
AB  - The effects of ozone and other photochemical oxidants on individual trees have
      been studied for several decades, but there has been much less research on the
      potential effects on entire forest ecosystems. Given that ozone and other
      oxidants affect the production and subsequent fate of biogenic volatile organic
      compounds that act as signalling molecules, there is a need for more detailed
      study of the role of oxidants in modifying trophic interactions in forests.
      Deposition of fine particulates to forests may act as a source of nutrients, but
      also changes leaf surface properties, increasing the duration of surface wetness
      and modifying the habitat for epiphytic organisms, leading to increased risks
      from pathogens. Even where this pathway contributes a relatively small input of
      nutrients to forests, the indirect effects on canopy processes and subsequent
      deposition to the forest floor in throughfall and litter may play a more
      important role that has yet to be fully investigated.

PMID- 18342420
TI  - Identification and enumeration of asbestos fibers in the mining environment:
      mission and modification to the Federal Asbestos Standard.
AB  - Since the promulgation of the first Federal Asbestos Standard by the Occupational
      Safety and Health Administration in 1972, other federal agencies have modified
      the standard to better carry on their own unique missions. The instruments used
      to identify and measure asbestos, the sampling protocol, and the criteria used to
      define asbestos, have been modified to some degree. The Mine Safety and Health
      Administration regulates and controls asbestos dust in the mining and mineral
      commodity industries. However, crushed stone and processed ores contain mineral
      fragments that are frequently difficult to distinguish from asbestos. Mineral
      nomenclature, instruments for particle analysis, and sampling strategy must be
      accommodated to some degree to make asbestos control workable and meaningful.
      Precedent in other agencies has made consideration of these changes possible.
      Newly identified amphibole asbestos minerals have further complicated the
      agency's regulatory charge. Changes in its Asbestos Standard are now being
      considered. Crushed taconite ore in the Eastern Mesabi highlights many of these
      issues.

PMID- 18342421
TI  - Producing effective knowledge agents in a pluralistic environment: what future
      for community health workers?
AB  - This paper is concerned with how poor populations can obtain access to trusted,
      competent knowledge and services in increasingly pluralistic health systems where
      unregulated markets for health knowledge and services dominate. The term
      "unregulated" here derives from the literature on the development of markets in
      low income countries and refers to the lack of state enforcement of formal laws
      and regulations. We approach this question of access through the changing roles
      and fortunes of community health workers over the last few decades and ask what
      kind of role they can be expected to play in the future. Community based health
      agents have been used in many settings as a way of filling gaps in service
      provision where more skilled personnel are not available. They have also
      fulfilled a more transformative role in broad based community development. We
      explore the reasons for the decline of programmes from the 1980s onwards. Using
      the specific experience of Bangladesh, the paper considers what lessons can be
      learned from past successes and failures and what needs to change to meet the
      challenges of 21st century health systems. These challenges are those of
      establishing credibility and legitimacy in a pluralistic environment and creating
      a sustainable livelihood strategy. The article concludes with a discussion of
      four potential models of community based health agents which are not necessarily
      exclusive: a generic agent that is closely linked to a reputable supervisory
      agency; a specialist cadre working with particular health conditions; an expert
      advocate; and a mobiliser or facilitator who can mediate between users and health
      markets.

PMID- 18342422
TI  - Incidence, staff awareness and mortality of patients at risk on general wards.
AB  - The aim of this study was to estimate the incidence, staff awareness and
      subsequent mortality of patients with abnormal vital signs on general wards in a
      Danish university hospital. DESIGN AND SETTINGS: Prospective data collection in
      two surgical and three medical wards at Herlev University Hospital, Copenhagen.
      Study personnel measured vital signs of all patients present on the wards at
      random points during the evening and interviewed nursing staff about patients
      with abnormal vital signs. Simplified medical emergency team (MET) calling
      criteria were used to define abnormal vital signs. INTERVENTIONS: None. RESULTS:
      During the 2-month data collection period, 877 patients were included in the
      study and 155 (18%) had abnormal vital signs. The 30-day mortality in this group
      was 13% compared to 5% among patients with normal vital signs (p<0.0001). Of the
      155 patients with abnormal signs, nursing staff were not aware of all of the
      patient's abnormalities in 67 (43%) cases. For 20 patients (13%), staff were
      aware of some of their abnormalities, while for 52 patients (34%), staff were
      aware of all their abnormalities. CONCLUSIONS: One out of five patients in the
      general wards developed abnormal vital signs during the 2-month study period and
      these patients had a 3-fold increased 30-day mortality. For almost half of the
      patients, nursing staff were unaware of their abnormal vital signs. Strategies to
      improve identification of patients at risk should be an initial step in
      preventing serious adverse events on the general wards.

PMID- 18342423
TI  - An fMRI study in monozygotic twins discordant for obsessive-compulsive symptoms.
AB  - To examine neurobiological changes underlying obsessive-compulsive symptoms (OCS)
      we examined intrapair differences in behavior and fMRI brain activation in
      monozygotic twins discordant for OCS, using a Tower of London planning paradigm.
      Despite only mild evidence for impairment at the behavioral level, twins with OCS
      showed significantly decreased brain activation during planning in dorsolateral
      prefrontal cortex, thalamus pulvinar, and inferior parietal cortex. These
      findings are consistent with the hypothesis of disturbed cortico-striato-thalamo
      cortical (CSTC) circuitry underlying OCS. In contrast to previous studies in
      patients with obsessive-compulsive disorder (OCD) we did not find robust evidence
      for reduced responsiveness in striatal brain regions. Together, these findings
      suggest that neurobiological mechanisms underlying OCS of environmental origin
      partly overlap with neurobiological changes in patients with OCD, where the
      disorder is likely caused by a combination of genetic and environmental
      influences. A difference between genetical and environmental etiologies may
      relate to the amount of reduced striatal responsiveness.

PMID- 18342424
TI  - The neural correlates of verbal encoding and retrieval in monozygotic twins at
      low or high risk for depression and anxiety.
AB  - Emotional processing and brain activation were examined during an encoding and
      recognition paradigm using emotionally salient words in a sample of monozygotic
      twin pairs at low or high risk for anxiety and depression. Discordant twin pairs
      were used to chart the effects of environmental risk factors and concordant twin
      pairs were used to chart the effects of genetic risk factors on performance and
      brain activation. Performance data did not support the existence of a negative
      response bias in subjects at high risk. At the neural level, however, increased
      left inferior frontal gyrus (LIFG) activation by negative words was found in high
      risk subjects, most prominently during recognition. Increased LIFG activity was
      found in subjects at high risk through either genetic or environmental risk
      factors. These results suggest that fMRI activation of the LIFG in a verbal
      emotional memory task may be a useful vulnerability marker for anxiety and
      depression.

PMID- 18342425
TI  - Partial molar volumes and adiabatic compressibilities of unfolded protein states.
AB  - We determined the partial molar volumes, V degrees , and adiabatic
      compressibilities, K degrees (S), of N-acetyl amino acids with neutralized
      carboxyl termini, N-acetyl amino acid amides, and N-acetyl amino acid
      methylamides between 18 and 55 degrees C. The individual compounds in the three
      classes have been selected so as to collectively cover the 20 naturally occurring
      amino acid side chains. We interpret our experimental results in terms of the
      volumetric contributions and hydration properties of individual amino acid side
      chains and their constituent atomic groups. We also conducted pH-dependent
      densimetric and acoustic measurements to determine changes in volume and
      compressibility accompanying protonation of the aspartic acid, glutamic acid,
      histidine, lysine, and arginine side chains. We use our resulting data to develop
      an additive scheme for calculating the partial molar (specific) volume and
      adiabatic compressibility of fully extended polypeptide chains as a function of
      pH and temperature. We discuss the differences and similarities between our
      proposed scheme and the reported additive approaches. We compare our calculated
      volumetric characteristics of the fully extended conformations of apocytochrome c
      and apomyoglobin with the experimental values measured in water (for
      apocytochrome c) or acidic pH (for apomyoglobin). At these respective
      experimental conditions, the two proteins are unfolded. However, the comparison
      between the calculated and experimental volumetric characteristics suggests that
      neither apocytochrome c nor apomyoglobin are fully unfolded and retain a sizeable
      core of solvent-inaccessible groups.

PMID- 18342426
TI  - Lipid membrane domain formation and alamethicin aggregation studied by
      calorimetry, sound velocity measurements, and atomic force microscopy.
AB  - An experimental study of phosphocholine membranes made from one lipid, from
      mixtures of DPPC and DLPC, and also from lipids and small amounts of alamethicin
      is presented. We used atomic force microscopy to investigate the spatial
      organization and structure of lipid domains and also of the defects induced by
      the peptide. Alamethicin was found to alter the state of lipids in the gel state
      in a way that domains of fluid lipids are formed close to the defects.
      Differential calorimetry revealed phase characteristics of the lipid mixtures and
      the effect of small amounts of alamethicin on the phase behavior. It was also
      shown that the sound velocity profiles of the membranes suspensions can be well
      calculated from the heat capacity traces of the samples. This result confirms the
      correlation between the mechanical properties and the specific heat of membrane
      systems.

PMID- 18342427
TI  - Using Earth Observation to update a Natura 2000 habitat map for a wetland in
      Greece.
AB  - The European Habitats Directive 92/43/EEC has defined the need for the
      conservation of habitats and species with the adoption of appropriate measures.
      Within the Natura 2000 ecological network of special areas of conservation,
      natural habitats will be monitored to ensure the maintenance or restoration of
      their composition, structure and extent. The European Space Agency's GlobWetland
      project has provided remotely sensed products for several Ramsar wetlands
      worldwide, such as detailed land cover-land use, water cycle and inundated
      vegetation maps. This paper presents the development and testing of an
      operational methodology for updating a wetland's habitat map using the
      GlobWetland products, and the evaluation of the extent to which GlobWetland
      products have contributed to the habitat map updating. The developed methodology
      incorporated both automated and analyst-supervised techniques to photo-interpret,
      delineate, refine, and evaluate the updated habitat polygons. The developed
      methodology was proven successful in its application to the wetland complex of
      the Axios-Loudias-Aliakmon delta (Greece). The resulting habitat map met the
      European and Greek national requirements. Results revealed that GlobWetland
      products were a valuable contribution, but source data (enhanced satellite
      images) were necessary to discriminate spectrally similar habitats. Finally, the
      developed methodology can be modified for original habitat mapping.

PMID- 18342428
TI  - Strategies to reduce the environmental impact of an aluminium pressure die
      casting plant: a scenario analysis.
AB  - This study explores a model (MIKADO) to analyse scenarios for the reduction of
      the environmental impact of an aluminium die casting plant. Our model calculates
      the potential to reduce emissions, and the costs associated with implementation
      of reduction options. In an earlier paper [Neto, B., Kroeze, C., Hordijk, L.,
      Costa, C., 2008. Modelling the environmental impact of an aluminium pressure die
      casting company and options for control. Environmental Modelling & Software 23
      (2) 147-168] we included the model description and explored the model by applying
      it to a plant in which no reduction options are assumed to be implemented (so
      called zero case, reflecting the current practice in the plant). Here, we perform
      a systematic analysis of reduction options. We analysed seven types of reduction
      strategies, assuming the simultaneous implementation of different reduction
      options. These strategies are analysed with respect to their potential to reduce
      emissions, environmental impact and costs associated with the implementation of
      options. These strategies were found to differ largely in their potential to
      reduce the environmental impact of the plant (10-87%), as well as in the costs
      associated with the implementation of options (-268 to +277keuro/year). We were
      able to define 11 strategies, reducing the overall environmental impact by more
      than 50%. Of these, two have net negative costs, indicating that the company may
      in fact earn money through their implementation.

PMID- 18342429
TI  - Editorial comment on: predicting the probability of deferred radical treatment
      for localised prostate cancer managed by active surveillance.

PMID- 18342430
TI  - Predicting the probability of deferred radical treatment for localised prostate
      cancer managed by active surveillance.
AB  - OBJECTIVES: Outcome data from a prospective study of active surveillance of
      localised prostate cancer were analysed to identify factors, present at the time
      of diagnosis, that predict subsequent radical treatment. METHODS: Eligible
      patients had clinical stage T1-T2a, N0-Nx, M0-Mx adenocarcinoma of the prostate
      with serum PSA<15 ng/ml, Gleason score <or= 7, primary Gleason grade <or= 3, and
      % positive biopsy cores (pbc) <or= 50%. Monitoring included serial PSA
      measurement and repeat prostate biopsies. Radical treatment was initiated in the
      event of biochemical progression (PSA velocity > 1 ng/ml/yr) or histological
      progression (primary Gleason grade >or= 4, or %pbc > 50%). Multivariate Cox
      regression analysis of baseline variables was performed with respect to time to
      radical treatment. RESULTS: The 326 men recruited from 2002 to 2006 have been
      followed for a median of 22 mo. Median age was 67 yr, and median initial PSA
      (iPSA) 6.4 ng/ml. Sixty-five patients (20%) had deferred radical treatment, 16
      (5%) changed to watchful waiting because of increasing comorbidity, 7 (2%) died
      of other causes, and 238 (73%) remain on surveillance. On multivariate Cox
      regression analysis, the free/total PSA ratio (p<0.001) and clinical T stage
      (p=0.006) were independent determinants of time to radical treatment.
      CONCLUSIONS: In addition to established prognostic factors, the free/total PSA
      ratio may predict time to radical treatment in patients with untreated, localised
      prostate cancer managed by active surveillance. This possibility warrants further
      study.

PMID- 18342431
TI  - Endothelial rehabilitation: the impact of chronic PDE5 inhibitors on erectile
      function and protein alterations in cavernous tissue of diabetic rats.
AB  - BACKGROUND: Diabetic men generally have reduced efficacy with PDE-5 inhibitors
      (PDE5i) for the treatment of erectile dysfunction (ED). OBJECTIVE: To determine
      whether chronic vardenafil exposure alters cavernous protein expression
      predicting improved erectile function in diabetes. DESIGN: Forty-two adult male
      Sprague Dawley rats with streptozotocin-induced (50mg/kg IP) diabetes for 4 wk,
      were exposed to either vehicle or vardenafil for 6 wk. Assessments compared the
      impact of vardenafil given at 1h and 20 h to erectile function and cellular
      alterations and downstream translation of cavernous protein profiles were aimed.
      INTERVENTION: Vehicle or vardenafil 0.5mg/kg/day by oral gavage for 6 wk.
      MEASUREMENTS: Erectile function, penile tissue morphology, protein expression and
      surface enhanced laser desorption/ionization time-of-flight mass spectrometry
      (SELDI) protein profiling were determined. RESULTS AND LIMITATIONS: A significant
      increase of intracavernous pressure was seen in both treatment arms compared to
      diabetic rats not receiving vardenafil. Immunohistochemical staining showed
      improved endothelial and smooth muscle cell staining with chronic vardenafil use.
      Western blot analysis demonstrated increased endothelial cell eNOS and smooth
      muscle alpha-actin protein content. SELDI protein profiling showed enhanced
      proteins expression at molecular weights of 14.7, 20, 41.9, 66.2, and 83.9 kDa in
      the chronically treated vardenafil group. CONCLUSIONS: Vardenafil was effective
      in treating diabetic-induced ED with the greatest effect achieved through chronic
      dosing, with no additive effect measured with the final acute dose. Changes noted
      in the histology and protein expression indicate that vardenafil may have a
      protective effect in this disease state. This finding may serve as a basis for
      further work evaluating the utility of chronic vardenafil dosing in diabetic men.

PMID- 18342433
TI  - The endocannabinoid system in vertebrate male reproduction: a comparative
      overview.
AB  - Prevailing studies emphasize on endocannabinoid activity in brain. However,
      sporadic evidences hint that endocannabinoid system controls male reproduction
      ranging from invertebrates to vertebrates. Although N-arachidonoylethanolamine is
      described in rat testis, its activity is still poorly known. Type-1 cannabinoid
      receptor and fatty acid amide hydrolase are particularly expressed in elongating
      spermatids and spermatozoa suggesting that endocannabinoids affect spermiogenesis
      and sperm physiology. Aim of this paper is to provide an analysis of the
      information available in vertebrates on male germ cell progression and sperm
      maturation mediated by the endocannabinoid system.

PMID- 18342434
TI  - Anandamide modulates growth and lipid metabolism in the zebrafish Danio rerio.
AB  - Endocannabinoids are known to be lipidic mediators with several biological
      functions as the stimulation of food intake and lipid metabolism via cannabinoid
      receptor CB1. Many evidences, such as the presence of CB1 mRNA in fat tissue,
      suggest a peripheral role for endocannabinoids in regulating lipogenesis and body
      weight in mammals. As animal models constitute good tools to study
      endocannabinoid system dynamics, we analyzed the role of the endocannabinoid
      anandamide (AEA) in modulating lipid metabolism and growth in zebrafish larvae
      and adults. The data obtained indicated that AEA administered via water modulates
      the transcription of its own receptor CB1, besides to up-regulate gene expression
      of sterol regulatory element binding protein (SREBP) and of the insulin-like
      growth factors (IGF-1 and IGF-2). The results here obtained represent the first
      evidence in fish of the endocannabinoid system involvement in lipid metabolism
      and growth.

PMID- 18342435
TI  - An autopsy case of acute multiple sclerosis (Marburg's type) during pregnancy.
AB  - We report a case of a 9-month pregnant woman who presented acute psychiatric and
      neurological symptoms with extensive involvement of the white matter on MRI and
      no oligoclonal bands on CSF examination. Despite high doses of intravenous
      steroids, plasmapheresis and immunosuppressive drugs, a fatal outcome (coma) was
      noted 8 months later. Neuropathological examination confirmed the diagnosis of
      Marburg's type of multiple sclerosis showing sharp-edged lesions of
      demyelination, giant astrocytes, numerous macrophages and little perivascular
      inflammation. We discuss the definition and limits of the Marburg entity with
      reference to acute disseminated encephalomyelitis, impact of pregnancy, unusual
      MRI features, neuropathology and treatment.

PMID- 18342436
TI  - Effects of curcumin on bladder cancer cells and development of urothelial tumors
      in a rat bladder carcinogenesis model.
AB  - Curcumin, a well-known dietary pigment derived from Curcuma longa, inhibited
      growth of several types of malignant cells both in vivo and in vitro. Its effects
      on cell proliferation and the induction of apoptosis in human bladder cancer cell
      lines and intravesical activity in a rat bladder tumor model were studied.
      Exposure of human bladder cancer cells to curcumin resulted in the induction of
      apoptotic cell death and caused cells to arrest in the G2/M phase. The anti
      apoptotic Bcl-2 and Survivin protein was downregulated by the curcumin treatment
      together with enhancement of the Bax and p53 expression. The inhibitory
      activities of curcumin were stronger than those of cisplatin and could not be
      prevented by catalase pretreatment in T24 cells. Clonal assay indicated large
      dose and short-term curcumin was lethal to bladder cancer cells. Moreover, the in
      vivo study revealed curcumin did induce apoptosis in situ, inhibit and slow the
      development of bladder cancer. These observations suggest that curcumin could
      prove an effective chemopreventive and chemotherapy agent for bladder cancer.

PMID- 18342437
TI  - Valorization of olive mill wastewater by its incorporation in building bricks.
AB  - This investigation deals with the possibility of incorporating the effluent
      resulting from olive oil extraction activity, known as olive oil mill wastewater
      (OMW), in the brick-making process. It was undertaken at an important Tunisian
      brickworks company. In this study, the OMW was mixed with clays following the
      same brick-making procedure used at the collaborative brickworks in Tunisia. The
      samples containing OMW were found to be comparable in forming/extrusion
      performance to a control product that used fresh water. The experimental products
      produced were tested for their comparative physical properties (volume shrinkage,
      water absorption, tensile strength of bricks, after firing at 920 degrees C and
      paste plasticity) in the unfired and fired states against a control representing
      the commercial product in the same factory. The results showed a significant
      increase in the volume shrinkage (10%) and the water absorption (12%), while the
      tensile strength remained constant. The maximum plasticity index value was found
      when incorporating 23% of OMW. This rate either maintained the physical and
      mechanical properties of bricks or improved them. The incorporation of OMW in
      bricks can represent a promising way to valorize this effluent, to rid the
      environment of a highly polluting wastewater and to save huge and precious
      amounts of water in a country where water shortage is a serious problem. This
      newly-prepared material has a double positive impact: it protects the environment
      and allows water economy.

PMID- 18342438
TI  - Potabilization of low NOM reservoir water by ultrafiltration spiral wound
      membranes.
AB  - Membrane technologies such as ultrafiltration offer an interesting alternative to
      integral treatment of surface water destined for human consumption. With this in
      mind, a pilot-scale ultrafiltration module was set up, equipped with spiral-wound
      polyethersulphone membranes (16.6m(2)) with an effective pore size of 0.05
      microm. The system operated continuously with a stable production of 0.9 m(3)/h
      (54 lmh) and a constant transmembrane pressure of -0.2 bar. The effluent obtained
      showed a total absence of faecal contamination indicators of both bacterial and
      viral origin, and also presented an excellent physico-chemical quality,
      independently of the quality of influent. Total aerobic bacteria counts revealed
      the problem of bacterial contamination in the membrane permeate zone, which could
      be controlled through daily chemical cleansing of the membrane. The chief problem
      presented by this type of system, applied as exclusive treatment, is low
      effectiveness in the retention of natural organic matter (NOM), in which respect
      the quality of the effluent was observed to depend on the quality of influent.
      This constitutes the principal limitation for applying the system to surface
      water due to the risk of disinfection by-products formation during the final post
      chlorination. However, spiral wound ultrafiltration (SWUF) membranes could be
      used for low NOM reservoir water total treatment offering several advantages over
      conventional technologies.

PMID- 18342439
TI  - Screening of native plants and algae growing on fly-ash affected areas near
      National Thermal Power Corporation, Tanda, Uttar Pradesh, India for accumulation
      of toxic heavy metals.
AB  - The present investigation was carried out to screen native plants growing in fly
      ash (FA) contaminated areas near National Thermal Power Corporation, Tanda, Uttar
      Pradesh, India with a view to using them for the eco-restoration of the area. A
      total number of 17 plants (9 aquatic, 6 terrestrial and 2 algal species) were
      collected and screened for heavy metal (Fe, Zn, Cu, Mo, B, Si, Al, Cr, Pb, Cd, Hg
      and As) accumulation. Differential accumulation of various heavy metals by
      different species of plants was observed. Hydrilla verticillata was found to be
      the most efficient metal accumulator among 9 aquatic plants, Eclipta alba among 6
      terrestrial plants and Phormedium papyraceum between 2 algal species. In general,
      the maximum levels of most metals were found in terrestrial plants while the
      lowest in algal species. However, translocation of the metals from root to shoot
      was found to be higher in aquatic plants than terrestrial ones. These results
      suggest that various aquatic, terrestrial and algal species of plants may be used
      in a synergistic way to remediate and restore the FA contaminated areas.

PMID- 18342440
TI  - Removal enhancement of 1-naphthol and 1-naphthylamine in single and binary
      aqueous phase by acid-basic interactions with polymer adsorbents.
AB  - In the present study removal performance of 1-naphthol and 1-naphthylamine from
      wastewater by single and binary adsorption was compared. Synergistic effects were
      investigated in single-solute, binary-solute, and the preloading adsorption
      systems at 293 K. Two commercial polystyrene adsorbents Amberlite XAD-4, a
      macroporous adsorbent, and NDA-100, a hyper-cross-linked adsorbent, were employed
      here for their frequent use in organic pollutants removal from contaminated
      waters. All the adsorption isotherms of 1-naphthol and 1-naphthylamine on both
      adsorbents were found to be well represented by the Langmuir equation. Adsorption
      capacity of the primary solute was enhanced in the presence of the co-solute,
      arising presumably from the synergistic effect caused by the laterally acid-base
      interaction between the adsorbed 1-naphthol and 1-naphthylamine molecules. Due to
      the stronger adsorption affinity of 1-naphthylamine to nonpolar adsorbents,
      adsorption enhancement of 1-naphthylamine in the presence of 1-naphthol is
      greater than that of 1-naphthol in the presence of 1-naphthylamine. The greater
      synergistic effect of 1-naphthol/1-naphthylamine equimolar mixtures on XAD-4 than
      that on NDA-100 partly results from the larger average pore size of the former
      adsorbent. A modified extended Langmuir model is proved to well describe the
      synergistic adsorption of 1-naphthol/1-naphthylamine equimolar mixtures in the
      binary-solute system. The synergistic coefficient of one adsorbate is linearly
      correlated with the amount of the other adsorbed on the adsorbent.

PMID- 18342441
TI  - A wintertime study of polycyclic aromatic hydrocarbons in PM(2.5) and PM(2.5-10)
      in Beijing: assessment of energy structure conversion.
AB  - Sixteen priority polycyclic aromatic (PAHs) in PM(2.5) and PM(2.5-10) samples
      collected from 20 sites in Beijing, China in December 2005 and January 2006 were
      analyzed to determine the composition, spatial distribution and sources. Total
      PAHs of PM(2.5) and PM(2.5-10) ranged from 5.2 to 1062.2 ng m(-3) and 7.6 to
      759.7 ng m(-3), respectively, categorized as heavier pollution. Among five kind
      of functional zones involved, industrial center, commercial area and village were
      heavily polluted. The mean concentration of PAHs in PM(2.5) of 407 ng m(-3) was
      1.67-fold of that in PM(2.5-10), which was relatively high compared to the
      previous studies (winter in 2001 and 2002). The most evident change was the
      increase of Flu, BbkF and InP, which are believed to be less harmful and related
      to the increasing use of clean energy. However, pollution distribution was
      spatially heterogeneous inside the city. The most polluted sites located in the
      southeast of the city. Unlike previous studies, fluoranthene was the most
      abundant component quantified, which could be associated with increasing use of
      natural gas as clean energy. Compositional analysis and principal component
      analysis (PCA) suggested that different kinds of combustion were the main source
      of the PAHs in PM, though contribution of coal was still evident.

PMID- 18342442
TI  - Olive mill wastewater triggered changes in physiology and nutritional quality of
      tomato (Lycopersicon esculentum mill) depending on growth substrate.
AB  - We have studied the changes in the physiology and nutritional quality of
      Lycopersicon esculentum exposed to olive mill wastewater (OMW) with regard to
      cultivation in sand and soil. Tomato plant performance decreased with increasing
      concentration of OMW to both substrates. Root was more sensitive to OMW than the
      upper parts of the plants, grown either in sand or in soil for 10 days and 3
      months, respectively, probably due to the direct OMW toxicity on roots as
      compared to other parts. Significant restriction on uptake and translocation of
      nutrients (K, Na, Fe, Ca and Mg) under OMW application was found. The decrease in
      the photochemical efficiency of PSII photochemistry in the light adapted state
      and the big decrease in photochemical quenching, indicate that OMW resulted in
      diminished reoxidation of Q(A)(-) and started to inactivate the reaction centers
      of PSII. The OMW supply on soil and sand, resulted in leaf water stress and
      lesser water use efficiency. Plants treated with high OMW concentration, produced
      fewer but bigger tomatoes as compared to plants treated with lower OMW
      concentration. Generally, fruit yield and nutritional value was inhibited under
      OMW application.

PMID- 18342443
TI  - Differential effects of overexpression of wild-type and mutant human alpha
      synuclein on MPP+-induced neurotoxicity in PC12 cells.
AB  - The genetic background and the pathogenesis of familial Parkinson's disease (PD)
      have not been fully elucidated. Two missense mutations in the alpha-synuclein
      gene, A30P and A53T, have been linked to familial PD. Increasing evidence
      suggests the involvement of alpha-synuclein, the dopamine transporter (DAT), and
      neurotoxins in the pathogenesis of PD, but their relationships to the death of
      nigral cells remains poorly understood. In the present study, we used the PC12
      cell line, a well recognized model of the nigral cell, to investigate the effects
      of overexpression of wild-type (WT) and mutant human alpha-synuclein on MPP+
      induced neurotoxicity. We found that overexpression of mutant alpha-synuclein
      enhanced the toxicity of MPP+ to PC12 cells and elevated intracellular reactive
      oxygen species (ROS) levels, whereas overexpression of WT alpha-synuclein
      protected PC12 cells against MPP+ toxicity and lowered ROS levels. Furthermore,
      assays of 131I-FP-beta-CIT binding with DAT membrane fractions showed that WT and
      mutant alpha-synuclein had different effects on the expression of DAT on the cell
      membrane following exposure to MPP+. WT alpha-synuclein reduced the toxic effect
      of MPP+ by facilitating DAT internalization, while both A30P and A53T alpha
      synuclein aggravated the toxic effect of MPP+ by reducing DAT internalization.
      These data indicate that alpha-synuclein regulates ROS levels and DAT surface
      expression in dopaminergic neurons, and thus changes the response of these cells
      to MPP+.

PMID- 18342444
TI  - Effect of the XbaI polymorphism of estrogen receptor alpha on postmenopausal gray
      matter.
AB  - The frequent polymorphism XbaI (A351G) in the estrogen receptor alpha (ERalpha)
      gene has been associated with some postmenopausal pathologies' risk such as
      Alzheimer's disease (AD) or cognitive decline. In the present study, we explored
      whether the XbaI polymorphism leads to different gray matter volumes using voxel
      based morphometry (VBM) on 20 magnetic resonance images of healthy postmenopausal
      women. Subjects carrying the less common XbaI/X allele were contrasted to non
      carriers in groups well balanced by relevant confounding variables. The XbaI/X
      allele carriers displayed clusters ranging from 9 to 28% of tissue reductions in
      the cerebellar (cluster size, z, stereotactic coordinates: 16 mm(3); 3.17; 14, 
      94, -38) and cerebral cortex, in particular in the occipital lobe (272 mm(3);
      3.76; -38,-68,-16), in the middle frontal gyrus (192 mm(3); 3.71; 38, 12, 38) and
      in the middle temporal gyrus, while the opposite comparison was negative. The
      XbaI/X allele in ERalpha gene is associated to smaller gray matter volumes of the
      cerebral and cerebellar cortex. This allele might increase the susceptibility for
      senile neurodegenerative conditions, being associated to smaller cerebral
      reserve.

PMID- 18342445
TI  - Up-regulation of reactivity and survival genes in astrocytes after exposure to
      short duration overpressure.
AB  - Gurdjian et al. proposed decades ago that pressure gradients played a major
      factor in neuronal injury due to impact. In the late 1950s, their experiments on
      concussion demonstrated that the principal factor in the production of concussion
      in animals was the sudden increase of intracranial pressure accompanying head
      injury. They reported the increase in pressure severity correlated with an
      increase in 'altered cells' resulting in animal death. More recently, Hardy et
      al. (2006) demonstrated the presence of transient pressure pulses with impact
      conditions. These studies indicate that short duration overpressure should be
      further examined as a mechanism of traumatic brain injury (TBI). In the present
      study, we designed and fabricated a barochamber that simulated overpressure noted
      in various head injury studies. We tested the effect of overpressure on
      astrocytes. Expressions of apoptotic, reactivity and survival genes were examined
      at 24, 48 and 72 h post-overpressure exposure. At 24 h, we found elevated levels
      of reactivity and survival gene expression. By 48 h, a decreased expression of
      apoptotic genes was demonstrated. This study reinforces the hypothesis that
      transient pressure acts to instigate the cellular response displayed following
      TBI.

PMID- 18342446
TI  - Sympathetic nerve fibers sprout into rat odontoblast layer, but not into dentinal
      tubules, in response to cavity preparation.
AB  - This study was designed to determine if sympathetic nerve fibers exist in
      dentinal tubules in rat normal dental pulp, and if they sprout into the dentinal
      tubules in response to artificial cavity preparation in dentin. Sympathetic nerve
      fibers in rat molar dental pulp were labeled using an anterograde axonal
      transport technique involving injection of wheat germ agglutinin-horseradish
      peroxidase (WGA-HRP) into the superior cervical ganglion (SCG). They were then
      observed using light and electron microscopes. In normal dental pulp (control),
      scattered WGA-HRP reaction products were observed in unmyelinated nerve endings
      in the odontoblast layer and subodontoblastic region. In injured pulp 3 weeks
      after cavity preparation, reaction products were about 1.8-times more plentiful
      in the above areas (versus control pulp). However, no labeled nerve fibers were
      observed in the dentinal tubules in either control or injured dental pulp. These
      results indicate that although sympathetic nerve fibers do indeed sprout in rat
      dental pulp in response to cavity preparation, they do not penetrate into the
      dentinal tubules in which postganglionic nerve endings derived from the SCG were
      not originally present.

PMID- 18342447
TI  - Prevalence and characteristics of opioid use in the US adult population.
AB  - This report describes the prevalence of opioid use in the US adult population,
      overall and in subgroups, the characteristics of opioid use, and concomitant
      medication use among opioid users. Data were obtained from the Slone Survey, a
      population-based random-digit dialing survey. One household member was randomly
      selected to answer a series of questions regarding all medications taken during
      the previous week. There were 19,150 subjects aged > or = 18 interviewed from
      1998 to 2006. Opioids were used 'regularly' ( > or = 5 days per week for > or = 4
      weeks) by 2.0%; an additional 2.9% used opioids less frequently. Regular opioid
      use increased with age, decreased with education level, and was more common in
      females and in non-Hispanic whites. The prevalence of regular opioid use
      increased over time and was highest in the South Central region. Nearly one-fifth
      of regular users had been taking opioids for > or = 5 years. Concomitant use of >
      or = 10 non-opioid medications was reported by 21% of regular opioid users
      compared to 4.5% of subjects who did not use opioids. Regular opioid users were
      more likely to use stool softeners/laxatives (9% vs. 2%), proton pump inhibitors
      (25% vs. 8%), and antidepressants (35% vs. 10%). From this nationally
      representative telephone survey, we estimate that over 4.3 million US adults are
      taking opioids regularly in any given week. Information on the prevalence and
      characteristics of use is important as opioids are one of the most widely
      prescribed classes of drugs in the US.

PMID- 18342448
TI  - Kelvin force microscopy at the second cantilever resonance: an out-of-vacuum
      crosstalk compensation setup.
AB  - We investigate the gap-voltage control loop in a Kelvin force microscopy setup
      with simultaneous non-contact topography imaging. The Kelvin controller
      electrostatically excites the second resonance of the cantilever at about 6.3
      times the first resonance frequency and adjusts the DC component of the gap
      voltage to cancel the oscillation amplitude at this frequency, while the non
      contact topography imaging is based on a frequency control loop that maintains a
      constant frequency of the mechanically excited first resonance of the cantilever
      by adjusting the tip-sample separation. Due to the self-excitation of the first
      resonance in our setup, it has to be considered that the electrostatic excitation
      at the second resonance frequency is applied to a closed feedback loop and cannot
      be considered as a simple superposition to the oscillation at the first resonance
      frequency. In particular, special care has to be taken about internal capacitive
      crosstalk between the tip bias and the cantilever deflection output signal. It is
      shown that such a coupling cannot be corrected by subtraction of a constant
      offset at the demodulator output since the crosstalk is sent into the self
      excitation loop and is multiplied by the closed loop transfer function. We
      present a circuit that actively compensates, outside the vacuum environment, the
      internal crosstalk by adding to the deflection output a dephased fraction of the
      electrostatic excitation signal.

PMID- 18342449
TI  - Brown-headed cowbirds (Molothrus ater) harbor Sarcocystis neurona and act as
      intermediate hosts.
AB  - We tested the hypothesis that brown-headed cowbirds (Molothrus ater) harbor
      Sarcocystis neurona, the agent of equine protozoal myeloencephalitis (EPM), and
      act as intermediate hosts for this parasite. In summer 1999, wild caught brown
      headed cowbirds were collected and necropsied to determine infection rate with
      Sarcocystis spp. by macroscopic inspection. Seven of 381 (1.8%) birds had grossly
      visible sarcocysts in leg muscles with none in breast muscles. Histopathology
      revealed two classes of sarcocysts in leg muscles, thin-walled and thick-walled
      suggesting two species. Electron microscopy showed that thick-walled cysts had
      characteristics of S. falcatula and thin-walled cysts had characteristics of S.
      neurona. Thereafter, several experiments were conducted to confirm that cowbirds
      had viable S. neurona that could be transmitted to an intermediate host and cause
      disease. Specific-pathogen-free opossums fed cowbird leg muscle that was enriched
      for muscle either with or without visible sarcocysts all shed high numbers of
      sporocysts by 4 weeks after infection, while the control opossum fed cowbird
      breast muscle was negative. These sporocysts were apparently of two size classes,
      11.4+/-0.7 microm by 7.6+/-0.4 microm (n=25) and 12.6+/-0.6 microm by 8.0+/-0
      microm (n=25). When these sporocysts were excysted and introduced into equine
      dermal cell tissue culture, schizogony occurred, most merozoites survived and
      replicated long term and merozoites sampled from the cultures with long-term
      growth were indistinguishable from known S. neurona isolates. A cowbird
      Sarcocystis isolate, Michigan Cowbird 1 (MICB1), derived from thin-walled
      sarcocysts from cowbirds that was passaged in SPF opossums and tissue culture
      went on to produce neurological disease in IFNgamma knockout mice
      indistinguishable from that of the positive control inoculated with S. neurona.
      This, together with the knowledge that S. falcatula does not cause lesions in
      IFNgamma knockout mice, showed that cowbird leg muscles had a Sarcocystis that
      fulfills the first aim of Koch's postulates to produce disease similar to S.
      neurona. Two molecular assays provided further support that both S. neurona and
      S. falcatula were present in cowbird leg muscles. In a blinded study, PCR-RFLP of
      RAPD-derived DNA designed to discriminate between S. neurona and S. falcatula
      showed that fresh sporocysts from the opossum feeding trial had both Sarcocystis
      species. Visible, thick-walled sarcocysts from cowbird leg muscle were positive
      for S. falcatula but not S. neurona; thin-walled sarcocysts typed as S. neurona.
      In 1999, DNA was extracted from leg muscles of 100 wild caught cowbirds and
      subjected to a PCR targeting an S. neurona specific sequence of the small subunit
      ribosomal RNA (SSU rRNA) gene. In control spiking experiments, this assay
      detected DNA from 10 S. neurona merozoites in 0.5g of muscle. In the 1999
      experiment, 23 of 79 (29.1%) individual cowbird leg muscle samples were positive
      by this S. neurona-specific PCR. Finally, in June of 2000, 265 cowbird leg muscle
      samples were tested by histopathology for the presence of thick- and thin-walled
      sarcocysts. Seven percent (18/265) had only thick-walled sarcocysts, 0.8% (2/265)
      had only thin-walled sarcocysts and 1.9% (5/265) had both. The other half of
      these leg muscles when tested by PCR-RFLP of RAPD-derived DNA and SSU rRNA PCR
      showed a good correlation with histopathological results and the two molecular
      typing methods concurred; 9.8% (26/265) of cowbirds had sarcocysts in muscle,
      7.9% (21/265) had S. falcatula sarcocysts, 1.1% (3/265) had S. neurona
      sarcocysts, and 0.8% (2/265) had both. These results show that some cowbirds have
      S. neurona as well as S. falcatula in their leg muscles and can act as
      intermediate hosts for both parasites.

PMID- 18342450
TI  - First report of Enterocytozoon bieneusi infection on a pig farm in the Czech
      Republic.
AB  - Enterocytozoon bieneusi infects humans and animals and can cause life-threatening
      diarrhea in immunocompromised people. The routes of transmission and its zoonotic
      potential are not fully understood. Pigs have been frequently reported to have E.
      bieneusi; therefore, we surveyed farm-raised pigs in the Czech Republic to
      determine its presence and genetic diversity. Spores were detected by microscopy
      in the faeces of 65 out of 79 examined animals (82%). A species-specific
      polymerase chain reaction (PCR) identified E. bieneusi in 94% of samples.
      Genotyping based on the ITS regions of the SSU rRNA gene identified that most
      pigs were infected with the species-specific genotype F, while two animals had
      the zoonotic genotype D and two had genotype Peru 9. This is the first report of
      E. bieneusi in swine in the Czech Republic, and demonstrated that most infections
      were with pig-specific genotypes. Nonetheless, swine may still play a role in the
      transmission of E. bieneusi to humans.

PMID- 18342451
TI  - Cognitive development and cortisol patterns in mid-life: findings from a British
      birth cohort.
AB  - Life-course associations among cortisol, cognitive development and educational
      attainment in the general population are not well understood. Using the 1958
      British birth cohort, our aim was to establish whether cortisol patterns at age
      45y are associated with childhood cognition and qualification level by adulthood.
      We measured salivary cortisol in 6527 individuals, 45min after waking (t(1)) and
      3h later (t(2)). To identify lack of morning cortisol peak and diurnal rhythm, we
      defined groups with: (a) t(1) cortisol in the bottom 5% of the distribution, or
      (b) 'flat't(1)-t(2) cortisol. Data on cognitive tests at ages 7, 11 and 16y and
      educational level were used. All childhood cognitive tests (maths, reading,
      verbal and non-verbal ability) were inversely associated, although not always
      significantly, with low t(1) and flat t(1)-t(2) cortisol. For example, at age 11
      for males, a standard deviation (SD) increase in maths score was associated with
      a 28% decreased odds for lowest t(1) cortisol, and with a 13% decreased odds of
      flat t(1)-t(2) cortisol. Associations for lowest t(1) and flat t(1)-t(2) cortisol
      were attenuated after adjustment for qualification level at 33y among males,
      although adjustment for childhood socio-economic position had little effect.
      Weaker associations for lowest t(1) cortisol among females were either unchanged
      or strengthened after adjustment for qualification level. Our results for males,
      but less so for females, are compatible with a causal relationship in either
      direction, namely from cortisol to cognitive ability or vice versa.

PMID- 18342452
TI  - Apocrine carcinomas of the breast in Turkish women: hormone receptors, c-erbB-2
      and p53 immunoexpression.
AB  - The aims of this study were twofold: (i) to determine the occurrence frequency of
      apocrine carcinoma of the breast (ApBCa) in Turkish breast cancer (BCa) patients;
      and (ii) to evaluate the expression of estrogen receptor (ER), progesterone
      receptor (PR), androgen receptor (AR), gross cystic disease protein-15 (GCDFP
      15), c-erbB-2, and p53 in these cases. Six hundred and twenty-six cases of BCa
      were studied immunohistochemically (streptoavidin-biotin horseradish peroxidase
      method). The results of ApBCa were compared with those of invasive ductal
      carcinoma not otherwise specified type (IDC-NOS) cases of similar grade. Thirteen
      cases of ApBCa were encountered, accounting for 2.1% of all BCa cases.
      Immunohistochemically, ApBCa positivity was as follows: GCDFP-15 (100%), ER
      (39%), PR (8%), AR (54%), p53 (39%), and c-erbB-2 (85%). In the IDC-NOS group,
      GCDFP-15* was expressed in less than 50% of the tumors. The occurrence
      frequencies of the other markers were as follows: ER (69%), PR (69%)*, AR (46%),
      c-erbB-2 (0%)*, and p53 (31%), (*) indicating significant differences between the
      two groups. For Turkish BCa patients, (i) the occurrence rate of ApBCa (2.1%) was
      high; and (ii) the following combination would allow for an immunohistochemical
      identification of ApBCa: GCDFP-15(+), c-erbB-2(+), and PR(-).

PMID- 18342453
TI  - Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a
      randomized and controlled double-blind crossover trial with long-term follow-up.
AB  - PURPOSE: Cancer patients who undergo radiotherapy remain at life-long risk of
      radiation-induced injury to normal tissues. We conducted a randomized,
      controlled, double-blind crossover trial with long-term follow-up to evaluate the
      effectiveness of hyperbaric oxygen for refractory radiation proctitis. METHODS
      AND MATERIALS: Patients with refractory radiation proctitis were randomized to
      hyperbaric oxygen at 2.0 atmospheres absolute (Group 1) or air at 1.1 atmospheres
      absolute (Group 2). The sham patients were subsequently crossed to Group 1. All
      patients were re-evaluated by an investigator who was unaware of the treatment
      allocation at 3 and 6 months and Years 1-5. The primary outcome measures were the
      late effects normal tissue-subjective, objective, management, analytic (SOMA
      LENT) score and standardized clinical assessment. The secondary outcome was the
      change in quality of life. RESULTS: Of 226 patients assessed, 150 were entered in
      the study and 120 were evaluable. After the initial allocation, the mean SOMA
      LENT score improved in both groups. For Group 1, the mean was lower (p = 0.0150)
      and the amount of improvement nearly twice as great (5.00 vs. 2.61, p = 0.0019).
      Similarly, Group 1 had a greater portion of responders per clinical assessment
      than did Group 2 (88.9% vs. 62.5%, respectively; p = 0.0009). Significance
      improved when the data were analyzed from an intention to treat perspective (p =
      0.0006). Group 1 had a better result in the quality of life bowel bother
      subscale. These differences were abolished after the crossover. CONCLUSION:
      Hyperbaric oxygen therapy significantly improved the healing responses in
      patients with refractory radiation proctitis, generating an absolute risk
      reduction of 32% (number needed to treat of 3) between the groups after the
      initial allocation. Other medical management requirements were discontinued, and
      advanced interventions were largely avoided. Enhanced bowel-specific quality of
      life resulted.

PMID- 18342454
TI  - Proposed rectal dose constraints for patients undergoing definitive whole pelvic
      radiotherapy for clinically localized prostate cancer.
AB  - PURPOSE: Although several institutions have reported rectal dose constraints
      according to threshold toxicity, the plethora of trials has resulted in multiple,
      confusing dose-volume histogram recommendations. A set of standardized,
      literature-based constraints for patients undergoing whole pelvic radiotherapy
      (RT) for prostate cancer would help guide the practice of prostate RT. The
      purpose of this study was to develop these constraints, demonstrate that they are
      achievable, and assess the corresponding rectal toxicity. METHODS AND MATERIALS:
      An extensive literature search identified eight key studies relating dose-volume
      histogram data to rectal toxicity. A correction factor was developed to address
      differences in the anatomic definition of the rectum across studies. The dose
      volume histogram constraints recommended by each study were combined to generate
      the constraints. The data from all patients treated with definitive intensity
      modulated RT were then compared against these constraints. Acute rectal toxicity
      was assessed. RESULTS: A continuous, proposed rectal dose-constraint curve was
      generated. Intensity-modulated RT not only met this constraint curve, but also
      was able to achieve at least 30-40% lower dose to the rectum. The preliminary
      clinical results were also positive: 50% of patients reported no acute bowel
      toxicity, 33% reported Grade 1 toxicity, and 17% reported Grade 2 toxicity. No
      patients reported Grade 3-4 acute rectal toxicity. CONCLUSIONS: In this study, we
      developed a set of proposed rectal dose constraints. This allowed for volumetric
      assessment of the dose-volume relationship compared with single dose-volume
      histogram points. Additional research will be performed to validate this
      threshold as a class solution for rectal dose constraints.

PMID- 18342455
TI  - Impact of traditional Samoan lifestyle (fa'aSamoa) on cancer screening practices.
AB  - BACKGROUND: The Samoan way of life, or the fa'aSamoa, is a collection of
      practices and rituals by which Samoans conduct their lives. The purpose of this
      study was to explore the possible influence of the fa'aSamoa on cancer prevention
      practices. METHODS: The investigators conducted six focus groups; three in
      Carson, California and three in Pago Pago, American Samoa among 60 men from the
      communities, matai (chiefs), faifeau (pastors). Using a discussion guide,
      bilingual Samoan moderators asked questions about the fa'aSamoa, how traditional
      cultural practices might influence cancer prevention, and whether certain aspects
      of the fa'aSamoa could be incorporated into cancer screening programs to improve
      screening rates. Through qualitative content analysis, the investigators
      identified major themes and came to a consensus about them. RESULTS: The mean age
      of the 60 participants was 61 years, all were married, 50 were born in American
      Samoa, and 10 were born in the Independent State of Samoa. Among the themes,
      three were particularly important. First, participants confirmed that the
      fa'aSamoa remains an important concept in Samoan life. Second, they believed that
      disease prevention was not an integral part of the fa'aSamoa. Indeed,
      traditionally modesty and reluctance to discuss personal issues may inhibit use
      of screening services. Despite these a beliefs, a third theme emerged. Because of
      the influence of the matai and faifeau in the fa'aSamoa, participants stressed
      that seeking input from these leaders could improve cancer prevention programs.
      CONCLUSION: The lack of emphasis on disease prevention in the fa'aSamoa may
      contribute to low cancer screening rates. However, other aspects of the culture,
      such as the respect for matai and faifeau could be incorporated into cancer
      prevention programs aimed at improving cancer control among Samoans.

PMID- 18342456
TI  - Comparative evaluation of successive extracts of leaf and stem bark of Albizzia
      lebbeck for mast cell stabilization activity.
AB  - Successive chloroform, methanol and water extracts of bark and leaves of Albizzia
      lebbeck were tested for its in vitro mast cell stabilizing effect against
      compound 48/80. Methanolic extract of leaf and methanolic and water extracts of
      bark have shown maximum activity comparable to that of disodium chromoglycate.

PMID- 18342457
TI  - Behavioural responses to photographs by pictorially naive baboons (Papio anubis),
      gorillas (Gorilla gorilla) and chimpanzees (Pan troglodytes).
AB  - This study assessed how pictorially naive nonhuman primates understand pictures.
      Fifty-five baboons with no prior exposure to pictures were trained to grasp a
      slice of banana presented against a pebble in a two alternative forced choice
      task. Post-training testing involved three stimulus pairs: (1) real banana slice
      vs. its picture, (2) the banana picture vs. a real pebble and (3) banana picture
      vs. a pebble picture which were presented twice. Preliminary data were also
      collected on naive gorillas (n=4) and chimpanzees (n=7) using the same procedure.
      Baboons revealed a preference for the food picture in (2) and (3) and often ate
      this stimulus, but the food item and its picture were accurately discriminated in
      (1). These results suggest that baboons mistook the pictorial stimulus and its
      referent, but processed the banana pictures as poor exemplars of the real banana
      category. Among apes, only gorillas ate the banana pictures, suggesting that
      picture-object confusion may also occur in this species. Findings are discussed
      as pertaining to the general issue of representational abilities in nonhuman
      primates, and its evolution.

PMID- 18342458
TI  - Effects of monetary reserves and rate of gain on human risky choice under budget
      constraints.
AB  - The energy-budget rule is an optimal foraging model that predicts that choice
      should be risk averse when net gains plus reserves meet energy requirements
      (positive energy-budget conditions) and risk prone when net gains plus reserves
      fall below requirements (negative energy-budget conditions). Studies have shown
      that the energy-budget rule provides a good description of risky choice in humans
      when choice is studied under economic conditions (i.e., earnings budgets) that
      simulate positive and negative energy budgets. In previous human studies,
      earnings budgets were manipulated by varying earnings requirements, but in most
      nonhuman studies, energy budgets have been manipulated by varying reserves and/or
      mean rates of reinforcement. The present study therefore investigated choice in
      humans between certain and variable monetary outcomes when earnings budgets were
      manipulated by varying monetary reserves and mean rates of monetary gain.
      Consistent with the energy-budget rule, choice tended to be risk averse under
      positive-budget conditions and risk neutral or risk prone under negative-budget
      conditions. Sequential choices were also well described by a dynamic optimization
      model, especially when expected earnings for optimal choices were high. These
      results replicate and extend the results of prior experiments in showing that
      humans' choices are generally consistent with the predictions of the energy
      budget rule when studied under conditions analogous to those used in nonhuman
      energy-budget studies, and that choice patterns tend to maximize reinforcement.

PMID- 18342459
TI  - Early alcohol experiences and adolescent mental health: a population-based study
      in Taiwan.
AB  - In this study, we examine whether adolescent emotional and behavior problems vary
      by history of early alcohol experiences. A national sample of 6974 alcohol-naive
      and 4337 alcohol-experienced youths aged 15-18 years were identified within the
      2004 National Survey of Illegal Drug Use among Adolescents in Taiwan. Four
      alcohol experience groups were created based on recency and frequency of alcohol
      use: (1) naive; never drank alcohol, (2) trial use; first and only consumption of
      alcohol occurred more than 6 months preceding the assessment, (3) past use;
      alcohol used on more than one occasion but had not had a drink in the 6 months
      prior to the assessment, and (4) current use; consumed alcohol more than once and
      drank within the 6 months preceding the interview. A Chinese adaptation of the
      Youth Self-Report (YSR) assessed eight behavior syndromes: withdrawn,
      anxious/depressed, somatic complaints, social problems, thought problems,
      attention problems, rule-breaking behavior, and aggressive behavior. Multivariate
      response models (GLM/GEE) were used to examine the relationship of alcohol
      experiences with emotional and behavior problems. Alcohol-using youth were more
      likely to experience several specific emotional or behavioral syndromes than
      their alcohol-naive counterparts. For example, youth with a history of alcohol
      use had an estimated 30-60% increase in the odds of experiencing items within the
      aggressive behavior syndrome as compared with alcohol-naive youth. The type of
      early alcohol involvement in adolescence may exert differential effects on
      emotions and behaviors expressed across and within syndromes; these may warrant
      distinctions in informing etiological research and preventive efforts.

PMID- 18342461
TI  - The use of atomic force microscopy to study the conditioning of micronised
      budesonide.
AB  - Patent literature describes "conditioning" techniques which employ organic
      vapours to recrystallise amorphous regions in micronised particles, with the aim
      of improving their processability and physico-chemical stability. This report
      describes a preliminary study investigating the efficacy of PhaseImaging atomic
      force microscopy (AFM) for the investigation of such processes. AFM phase images
      demonstrated variation in mechanical properties across the surface of milled
      budesonide particles, which diminished upon exposure to ethanol vapour. No
      variation was seen in phase images of unmilled budesonide. Dynamic vapour
      sorption confirmed the presence amorphous material in the milled sample and its
      subsequent recrystallisation following exposure to ethanol vapour under the same
      conditions as those used in the AFM experiment. It was therefore hypothesised
      that variation in the phase images indicated the presence of amorphous regions
      which were subsequently conditioned. PhaseImaging AFM may therefore be a useful
      method for the study of conditioning techniques, enabling the efficacy and
      kinetics of the process to be observed.

PMID- 18342460
TI  - Relationship between BMD, dental panoramic radiographic findings and biochemical
      markers of bone turnover in diagnosis of osteoporosis.
AB  - OBJECTIVE: Mandibular indices, measured on panoramic radiographs, may be useful
      screening implements for low skeletal bone mass density (BMD). Recent studies
      suggest that radiographic examination of mandible may constitute an effective
      process for the early diagnosis of osteoporosis. Biochemical markers of bone
      turnover may be of value for prediction of individual bone loss and they may help
      in predicting risk of fracture in elderly women. In contrast to the vast
      information available on dental radiographic findings and BMD only scarce data
      exist on the relationship between panoramic mandibular indices and biochemical
      markers. The aim of this study was to examine the diagnostic performance of
      dental panoramic radiography and biochemical markers of bone turnover in relation
      to BMD at the spine in a group of postmenopausal women. SUBJECTS AND METHODS: An
      assessment of the number of lost teeth, mandibular cortical width (MCW) at the
      mental region and morphologic classification of mandibular inferior cortex (MIC
      grade) was performed on dental panoramic radiographs in a group of 141
      postmenopausal women 38-81 years of age. BMD at the lumbar spine was measured by
      dual energy X-ray absorptiometry. BMD values were categorized as normal (T-score
      greater than 1.0), and as indicative of osteopenia (T-score -1.0 to -2.5) or
      osteoporosis (T-score less than -2.5) according to the World Health Organization
      classification. Serum bone alkaline phosphatase (BAP) was measured with an enzyme
      immunoassay. Cross-linked N-telopeptides of type I collagen (NTx) corrected for
      creatinine secretion, was measured with a competitive-inhibition enzyme-linked
      immunosorbent assay ELISA. RESULTS: In our study, a decrease in MCW by 1mm
      increases the likelihood of osteopenia or osteoporosis to 47% (p-value<0.05),
      having taken into consideration the effect of the years elapsed since menopause.
      The increase of alkaline phosphatase (ALP) per unit increase the likelihood of
      osteopenia or osteoporosis to 14% (p-value<0.05), having checked the effect of
      the years since menopause. A decrease in MCW by 1mm increases the likelihood of
      moderately or severely eroded cortex to 97% (p-value<0.001). The increase in ALP
      per 1 unit increases the likelihood of moderate or severe erosion per 10% (p
      value<0.05), taking into account the years since menopause. CONCLUSIONS: Our
      results suggest that dentists have sufficient clinical and radiographic
      information that enables them to play a significant role in early diagnosis of
      osteoporosis in postmenopausal women. Panoramic radiographs and biochemical
      markers of bone turnover may be of value for prediction of individual bone loss
      and they may help in predicting risk of fracture in elderly women.

PMID- 18342462
TI  - Water-immiscible room temperature ionic liquids (RTILs) as drug reservoirs for
      controlled release.
AB  - Water-immiscible room temperature ionic liquids (RTILs) have a largely unexplored
      potential as pharmaceutical solvents and reservoirs. This paper explores some
      relevant properties of the hexafluorophosphate (PF6(-)) salts of butyl, hexyl and
      octyl-3-methylimidazolium cations (BMIM, HMIM, OMIM, respectively). The dodecyl
      analogue is solid at room temperature, but its melting point can be lowered by
      addition of the lower homologues. Although water-immiscible, the liquids absorb
      water to an extent depending on their structure, the higher alkyl analogues
      having a lower affinity for absorbed water. The RTIL/water partition coefficients
      of sucrose, penicillin V potassium, dexametasone, progesterone and dehydro
      epiandrosterone have been compared with octanol-water coefficients. The
      viscosities of the salts were measured in anhydrous, water-saturated and
      intermediate states. The PF6(-) ionic liquids display a low and decreasing
      aqueous solubility as the alkyl chain length is increased: 0.035 moll(-1) (BMIM),
      0.032 moll(-1) (HMIM) and 0.09 moll(-1) (OMIM). The release of sucrose and
      dexametasone from RTIL reservoirs into water can be prolonged over 48 h.
      Saturated solutions of these RTILs show little toxicity towards Caco-2 cells,
      although the OMIM derivative, which is more surface-active, has a small effect on
      cell viability.

PMID- 18342463
TI  - Coding of FM sweep trains and twitter calls in area CM of marmoset auditory
      cortex.
AB  - The primate auditory cortex contains three interconnected regions (core, belt,
      parabelt), which are further subdivided into discrete areas. The caudomedial area
      (CM) is one of about seven areas in the belt region that has been the subject of
      recent anatomical and physiological studies conducted to define the functional
      organization of auditory cortex. The main goal of the present study was to
      examine temporal coding in area CM of marmoset monkeys using two related classes
      of acoustic stimuli: (1) marmoset twitter calls; and (2) frequency-modulated (FM)
      sweep trains modeled after the twitter call. The FM sweep trains were presented
      at repetition rates between 1 and 24 Hz, overlapping the natural phrase frequency
      of the twitter call (6-8 Hz). Multiunit recordings in CM revealed robust phase
      locked responses to twitter calls and FM sweep trains. For the latter, phase
      locking quantified by vector strength (VS) was best at repetition rates between 2
      and 8 Hz, with a mean of about 5 Hz. Temporal response patterns were not strictly
      phase-locked, but exhibited dynamic features that varied with the repetition
      rate. To examine these properties, classification of the repetition rate from the
      temporal response pattern evoked by twitter calls and FM sweep trains was
      examined by Fisher's linear discrimination analysis (LDA). Response
      classification by LDA revealed that information was encoded not only by phase
      locking, but also other components of the temporal response pattern. For FM sweep
      trains, classification was best for repetition rates from 2 to 8 Hz. Thus, the
      majority of neurons in CM can accurately encode the envelopes of temporally
      complex stimuli over the behaviorally-relevant range of the twitter call. This
      suggests that CM could be engaged in processing that requires relatively precise
      temporal envelope discrimination, and supports the hypothesis that CM is
      positioned at an early stage of processing in the auditory cortex of primates.

PMID- 18342464
TI  - Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and
      alter cell morphology.
AB  - Matrix metalloproteinases (MMPs) play vital roles in many pathological
      conditions, including cancer, cardiovascular disease, arthritis and inflammation.
      Modulating MMP activity may therefore be a useful therapeutic approach in
      treating these diseases. Qing-Kai-Ling is a popular Chinese anti-inflammatory
      formulation used to treat symptoms such as rheumatoid arthritis, acute
      hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract
      infection. In this paper, we report that one of the components of Qing-Kai-Ling,
      Fructus gardeniae, strongly inhibits MMP activity. The IC50 values for the
      primary herbal extract and water extract against MMP-16 were 32 and 27 microg/ml,
      respectively. In addition, we show that the herbal extracts influence HT1080
      human fibrosarcoma cell growth and morphology. These data may provide molecular
      mechanisms for the therapeutic effects of Qing-Kai-Ling and herbal medicinal
      Fructus gardeniae.

PMID- 18342465
TI  - Study of the antitumor potential of Bidens pilosa (Asteraceae) used in Brazilian
      folk medicine.
AB  - AIM OF THE STUDY: Bidens pilosa (L.) (Asteraceae) is a medicinal plant
      traditionally used in Brazil for treating conditions that can be related to
      cancer. Therefore the present study was carried out to evaluate the antitumor
      activity of extracts obtained from the aerial parts of this plant species.
      MATERIALS AND METHODS: The crude hydroalcoholic extract (HAE) (water:alcohol,
      6:4) and solvent fractions (chloroform=CHCl3,ethyl acetate=EtOAc, methanol=MeOH)
      were assessed for cytotoxicity assay by the brine shrimp and hemolytic, MTT and
      NRU assays. The antiproliferative potential of the crude extract and fractions
      was investigated in vivo using the Ehrlich ascites carcinoma (EAC) in isogenic
      Balb/c mice that were administered intraperitoneally 150 and 300 mg/kg body
      weight per day for nine days beginning 24 h after tumor inoculation. RESULTS: In
      in vitro cytotoxicity using Ehrlich ascites carcinoma cell line assay CHCl3
      extract proved to be more toxic than the crude HAE with an IC(50) of 97+/-7.2 and
      83+/-5.2 microg/mL to NRU and MTT, respectively. Histomorphological evaluations
      indicated that the treatment with CHCl3 and HAE extracts significantly reduced
      (P<0.05) body weight, abdominal circumference, tumor volume, packed cell volume
      and viable cell count, when compared to EAC control group. Furthermore, nonviable
      tumor cell count increased significantly (P<0.01) only under treatment with CHCl3
      or HAE, and this was accompanied by a marked percentage increase in life span
      (54.2 and 41.7%, respectively). Biochemical assays revealed that CHCl3 and HAE
      extracts were also able to decrease serum LDH activity (39.5 and 30.6%) and GSH
      concentration (94.6 and 50.7%) in ascitic fluid, respectively. CONCLUSION: The
      chloroform fraction showed the best and methanolic the worst antitumor activity.

PMID- 18342466
TI  - [Pancreatitis with hepatitis revealing a systemic lupus erythematosus].
AB  - We report the case of a 27 years old woman, hospitalised for non necrotizing
      acute pancreatitis and cytolytic hepatitis. No usual aetiology was found.
      Associated cutaneous manifestations and biologic abnormalities were the clue to
      the diagnosis of lupus-related pancreatitis and hepatitis. Disease course was
      uneventful with systemic corticotherapy and antimalarials. Pancreatitis is a very
      uncommon manifestation of systemic lupus erythematosus. Its incidence is
      estimated at 1.1/1000 lupus per year. Ten cases of lupus-revealing pancreatitis
      have been reported. This case is the first one associated with a lupus-related
      hepatitis. It is important to seek specific cutaneous signs to ascertain the
      diagnosis as soon as possible and avoid useless and deleterious investigations.
      In our patient, the favourable evolution of the pancreatitis with corticosteroids
      adds further evidence to the idea that lupus-related pancreatitis is not a side
      effect of corticosteroid therapy.

PMID- 18342467
TI  - Age and natural metabolically-intensive behavior affect oxidative stress and
      antioxidant mechanisms.
AB  - Flying honey bees have among the highest mass-specific metabolic rates ever
      measured, suggesting that their flight muscles may experience high levels of
      oxidative stress during normal daily activities. We measured parameters of
      oxidative stress and antioxidant capacity in highly metabolic flight muscle and
      less active head tissue in cohorts of age-matched nurse bees, which rarely fly,
      and foragers, which fly several hours per a day. Naturally occurring foraging
      flight elicited an increase in flight muscle Hsp70 content in both young and old
      foragers; however catalase and total antioxidant capacity increased only in young
      flight muscle. Surprisingly, young nurse bees also showed a modest daily increase
      in Hsp70, catalase levels and antioxidant capacity, and these effects were likely
      due to collecting the young nurses soon after orientation flights. There were no
      differences in flight muscle carbonyl content over the course of daily activity
      and few differences in Hsp70, catalase, total antioxidant capacity and protein
      carbonyl levels in head tissue regardless of age or activity. In summary, honey
      bee flight likely produces high levels of reactive oxygen species in flight
      muscle that, when coupled with age-related decreases in antioxidant activity may
      be responsible for behavioral senescence and reduced longevity.

PMID- 18342468
TI  - Extracellular Gd-CA: differences in prevalence of NSF.
AB  - Until recently it was believed that extracellular gadolinium-based contrast
      agents were safe for both the kidneys and all other organs within the dose range
      up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some
      gadolinium-based contrast agents may trig the development of nephrogenic systemic
      fibrosis, a generalized fibrotic disorder, in renal failure patients. As no
      prospective studies can be performed we must rely on retrospective data. From
      those data it is obvious that the prevalence of NSF is significantly higher after
      the unstable agent gadodiamide than after any other gadolinium-based agent (3-7%
      versus 0-1% per injection) in patients with reduced renal function. Prevalence
      after exposure to two gadodiamide injections is as high as 36% in patients with
      chronic kidney disease (CKD) stage 5. No report of NSF after the most stable
      agents has been reported in the peer-reviewed literature documenting that there
      is a difference between the various agents regarding triggering NSF.

PMID- 18342469
TI  - Reducing the risk of iodine-based and MRI contrast media administration:
      recommendation for a questionnaire at the time of booking.
AB  - This paper presents a practical questionnaire to be used when a contrast medium
      examination is requested. The questionnaire is based on the guidelines from the
      European Society of Urogenital Radiology. Its aim is to identify patients at
      increased risk of clinically relevant renal and non-renal adverse reactions to
      iodine-based and MRI contrast agents. The questionnaire should be completed by
      the referring physician when the examination is requested.

PMID- 18342470
TI  - Nephrogenic systemic fibrosis--implications for nephrologists.
AB  - Nephrogenic systemic fibrosis (NSF) is a debilitating disorder seen in-patient
      with advanced chronic kidney disease (CKD). Recent evidence suggests a link
      between NSF and the administration of gadolinium-based contrast agents (Gd-CA).
      In addition, other risk factors have also been suggested to facilitate the
      development of NSF in this population after Gd-CA. These include metabolic
      acidosis, high-dose erythropoietin therapy, and the altered mineral metabolism of
      CKD. While it is possible that these factors may increase the risk of NSF after
      Gd-CA exposure, they may also simply reflect conditions that increase the risk of
      getting exposed to Gd-CA, particularly at high doses. Furthermore, given the risk
      of NSF in CKD, physicians must weigh the risks of NSF versus the risk of contrast
      induced nephropathy (CIN) with iodinated agents in this population. In this
      review, we will provide a nephrologist's perspective on these issues and the
      nephrologist's role in the prevention of NSF.

PMID- 18342471
TI  - FDG PET scan strategies and long-term outcomes after first-line therapy in
      Hodgkin's disease.
AB  - BACKGROUND: The use of positron emission tomography with fluoro-deoxy-glucose
      (FDG PET) in Hodgkin's disease (HD) is continuing to expand worldwide, with
      response assessment after completion of therapy being its most widely utilized
      application. A positive scan has been associated with high relapse rates and
      disease progression. METHODS: A decision analysis was performed to determine the
      long-term impact of FDG PET restaging both with and without computed tomography
      (CT) in terms of the 5-year progression-free survival (5yrPFS). Outcomes and
      utilities were based on published data. The first strategy involved CT restaging
      after first-line therapy, with or without subsequent FDG PET, while the second
      strategy used FDG PET scan alone. All positive test required histological
      examination. Upon histological confirmation of active lymphoma, patients were
      considered candidates for autologous transplantation and long-term outcomes were
      retrieved. The expected clinical benefit of the two strategies was calculated and
      depicted, along with the mean costs. One-way and two-way sensitivity analyses
      were performed to ensure the validity of the results. RESULTS: CT restaging plus
      FDG PET when residual mass is detected, results in a 2% benefit at 5yrPFS at
      baseline compared to FDG PET-alone restaging and remains positive for a wide
      range of probabilities. This strategy reduces the average cost by euro 1863 per
      patient, including costs of biopsy and autologous transplantation. CONCLUSION: A
      more conservative approach that includes CT restaging after first-line therapy
      and FDG PET scan only on residual mass, is the preferred strategy in HD.
      Furthermore it appears to confer the maximal diagnostic yield along with a
      substantial reduction in the mean cost.

PMID- 18342472
TI  - Acute non-traumatic marrow edema syndrome in the knee: MRI findings at
      presentation, correlation with spinal DEXA and outcome.
AB  - PURPOSE: The aim of the study was to present the MRI findings of non-traumatic
      edema-like lesions presented acutely in the adult knee and to correlate them with
      the 3-year outcome and the bone mineral density (BMD) in the spine. MATERIALS AND
      METHODS: Ninety-eight patients (40 men, 58 women, mean age 60.1+/-11 years, age
      range 27-82 years), were followed up clinically as well as with MR imaging, when
      indicated, for at least 3 years. Patients were classified according to
      presentation in 3 groups (A: bone marrow edema (BME), B: BME and subchondral
      fracture, C: BME and articular collapse) and according to outcome in 2 groups (A:
      reversible BME, B: articular collapse). BMD measurements of the spine were
      carried out in males over 70 and females over 60 years old using DEXA. RESULTS:
      The isolated BME pattern was observed in 64.3% (Group A), subchondral fractures
      without articular collapse in 11.2% (Group B) and articular collapse in 24.5%
      (Group C). Significant differences were found among the 3 groups at presentation,
      regarding the age, sex, BMD, affected area and duration of symptoms prior to
      imaging (p<0.05). Localization of the lesions in the weight-bearing areas of the
      knee was shown in 100% of C, in 90.9% of B and in 50.8% of A. The duration of
      symptoms prior to imaging was longer in C (7.6+/-2.8m) than in A (2.5+/-1.7m) and
      B (4.0+/-3.2m) (p<0.05). Group B progressed to articular collapse in 45.5%, the
      rest demonstrating a favourable outcome. Group C showed clinical improvement in
      75% and persistent symptoms that required knee arthroplasty in 25% of cases.
      Articular collapse was the final outcome in 29.6% and transient BME in 70.4% of
      patients. These two groups showed significant differences regarding the age (p
      approximately 0), sex (p=0.002), low BMD (p=0.004), affected area (p
      approximately 0), presence of subchondral sparing (p approximately 0), duration
      of symptoms prior to imaging (p approximately 0), time from onset of symptoms to
      the final outcome (p approximately 0) and need for arthroplasty (p=0.001). None
      of the patients with transient BME syndrome eventually progressed to articular
      collapse. CONCLUSION: In the context of acute non-traumatic knee BME, the age and
      sex of the patient, the duration of symptoms before imaging, the pattern of BME,
      and the BMD appear to correlate with the final outcome.

PMID- 18342473
TI  - Spatio-temporal pattern of vestibular information processing after brief caloric
      stimulation.
AB  - Processing of vestibular information at the cortical and subcortical level is
      essential for head and body orientation in space and self-motion perception, but
      little is known about the neural dynamics of the brain regions of the vestibular
      system involved in this task. Neuroimaging studies using both galvanic and
      caloric stimulation have shown that several distinct cortical and subcortical
      structures can be activated during vestibular information processing. The insular
      cortex has been often targeted and presented as the central hub of the vestibular
      cortical system. Since very short pulses of cold water ear irrigation can
      generate a strong and prolonged vestibular response and a nystagmus, we explored
      the effects of this type of caloric stimulation for assessing the blood-oxygen
      level-dependent (BOLD) dynamics of neural vestibular processing in a whole-brain
      event-related functional magnetic resonance imaging (fMRI) experiment. We
      evaluated the spatial layout and the temporal dynamics of the activated cortical
      and subcortical regions in time-locking with the instant of injection and were
      able to extract a robust pattern of neural activity involving the contra-lateral
      insular cortex, the thalamus, the brainstem and the cerebellum. No significant
      correlation with the temporal envelope of the nystagmus was found. The temporal
      analysis of the activation profiles highlighted a significantly longer duration
      of the evoked BOLD activity in the brainstem compared to the insular cortex
      suggesting a functional de-coupling between cortical and subcortical activity
      during the vestibular response.

PMID- 18342474
TI  - Risk factors for Candida non-albicans candidemia.

PMID- 18342475
TI  - Determination of moxifloxacin anaerobic susceptibility breakpoints according to
      the Clinical and Laboratory Standards Institute guidelines.
AB  - A summary of the key data presented to Clinical and Laboratory Standards
      Institute (CLSI, formerly National Committee for Clinical and Laboratory
      Standards) in determination of moxifloxacin anaerobic breakpoints is presented.
      The breakpoint analysis required review of a variety of data, including
      bacteriologic and clinical outcomes by MIC of anaerobic isolates from prospective
      clinical trials in patients with complicated intra-abdominal infections, human
      and animal pharmacokinetic/pharmacodynamic (PK/PD) information and in vitro
      models, MIC distributions of indicated organisms, and animal model efficacy data
      for strains with MIC values around prospective breakpoints. The compilation of
      the various components of this breakpoint analysis supports the US Food and Drug
      Administration (FDA) and CLSI moxifloxacin anaerobic breakpoints of < or =2 mg/L
      (susceptible), 4 mg/L (intermediate), and > or =8 mg/L (resistant), and provides
      information to European investigators for interpretation of MICs prior to
      establishment of the European Committee on Antimicrobial Susceptibility Testing
      breakpoints.

PMID- 18342476
TI  - Tigecycline for treating bloodstream infections: a critical analysis of the
      available evidence.

PMID- 18342477
TI  - Neuroprotective effects of SB-415286 on hydrogen peroxide-induced cell death in
      B65 rat neuroblastoma cells and neurons.
AB  - Glycogen synthase kinase-3 (GSK-3) is involved in the pathogenesis of several
      neurodegenerative diseases. In addition, as oxidative stress has been implicated
      in all neurodegenerative disorders, the inhibition of both pathways offers a
      potential strategy for preventing or delaying neurodegeneration. We examined the
      cytoprotective effects of lithium and SB-415286, two inhibitors of GSK-3, using a
      rat B65 cell line and also in cerebellar granule cells (CGN). H(2)O(2) decreased
      the inactive form of GSK-3 (phospho-GSK-3 at Ser9), as measured by immunoblot
      experiments involving an antibody against the inactive form of the enzyme.
      Moreover, lithium inhibited this effect. While SB-415286 exerted a protective
      effect, lithium did not attenuate the toxic effects of H(2)O(2) (1mM). We then
      examined those mechanisms implicated in the protective effects of SB-415286. When
      we analyzed reactive oxygen species (ROS) production using the fluorescent probe
      2,7-dichlorodihydrofluorescein diacetate in B65 cells, as well as in CGN, we
      found that SB-415286 strongly reduced DCF fluorescence. Lithium, however, did not
      exhibit any antioxidant properties. We conclude that the GSK-3 inhibitor SB
      415286 has antioxidant properties, which may explain the cytoprotective effects
      against H(2)O(2) damage. Furthermore, inhibition of GSK-3 activity was not
      involved in this protective effect.

PMID- 18342478
TI  - Lifetime physical and sexual abuse and substance use treatment outcomes in men.
AB  - Although lifetime physical and sexual abuse are common among substance use
      disorder (SUD) patients, few studies have examined the impact of abuse on
      treatment outcomes, particularly for men. Men with lifetime physical (n = 49),
      sexual (n = 49), or no abuse (n = 117) history were assessed at entry to
      outpatient SUD treatment and at 6 and 12 months postintake. Men with a history of
      physical or sexual abuse had more severe drug problems at intake, but by 6
      months, there were no group differences in drug use. However, relative to men
      without an abuse history, men with a sexual abuse history had more severe
      psychiatric problems at all three time points and were more likely to report
      significant suicidality at intake and 6 months. Findings suggest that men with a
      history of sexual abuse benefit from SUD treatment, but additional intervention
      may be warranted to remedy persisting psychiatric distress.

PMID- 18342479
TI  - Comparison of cannabis and tobacco withdrawal: severity and contribution to
      relapse.
AB  - This naturalistic telephone survey study compared perceptions of withdrawal
      severity in 67 daily cannabis users and 54 daily tobacco cigarette smokers who
      made quit attempts during the prior 30 days. A Withdrawal Symptom Checklist
      assessed the severity of abstinence symptoms and a Likert scale assessed
      perceived relations between abstinence symptoms and relapse. A composite
      Withdrawal Discomfort Score did not differ significantly between groups (M = 13.0
      for cannabis, vs. M = 13.2 for tobacco). Individual symptom severity ratings were
      also of similar magnitude, except craving and sweating were slightly higher for
      tobacco. Both groups reported that withdrawal contributed substantially to
      relapse, and the strength of these ratings was similar across groups. The diverse
      convenience sample examined in this study adds external validity and
      generalizability to prior studies that included only users not planning to quit
      or excluded many common types of cannabis users. The comparable withdrawal
      experience from these heterogeneous cannabis and tobacco users supports previous
      findings from controlled laboratory studies and indicates that real-world,
      frequent cannabis users perceive that withdrawal symptoms negatively affect their
      desire and ability to quit.

PMID- 18342480
TI  - Outcomes and survival after laparoscopic gastrectomy for adenocarcinoma. Analysis
      on 65 patients operated on by conventional or robot-assisted minimal access
      procedures.
AB  - AIMS: Despite laparoscopic surgery for gastric cancer has gained worldwide
      acceptance, long term results and survival are seldom reported. This study was
      designed to assess long term outcomes after laparoscopic gastrectomy with D2
      dissection. The short term results of conventional and robot-assisted minimally
      invasive procedures were also examined. PATIENTS AND METHODS: The charts of 65
      patients who underwent laparoscopic surgery for non-metastatic adenocarcinoma
      were reviewed retrospectively. This series included 35 patients with early
      gastric cancer (EGC) and 30 with advanced gastric cancer (AGC). A 4/5
      laparoscopic subtotal gastrectomy (LSG) with D2 nodal clearance was the procedure
      of choice for distal cancers. Laparoscopic total gastrectomy (LTG) with modified
      D1 lymphadenectomy was performed for mid-proximal EGC. RESULTS: Sixty
      gastrectomies were carried out laparoscopically, 56 LSG and 4 LTG. Conversion to
      laparotomy was required in 5 patients with distal cancer. No intraoperative
      complication was registered. Morbidity included 2 duodenal leaks that healed
      conservatively. Two postoperative deaths were registered. An average number
      31.3+/-8.8 lymph nodes were collected. The mean hospital stay was 10 days (range
      7-24). The mean follow up was 30 months (range 2-86) and the cumulative overall 5
      year survival rate was 78%. Survival at 5 years for EGC was 94% and survival at 4
      years for AGC was 53% (57% for non-converted patients). CONCLUSIONS: Laparoscopic
      gastrectomy for cancer represents a valid alternative to open surgery with
      minimal morbidity and acceptable long term survival. Considering the risk of
      preoperative under diagnoses a D2 lymphadenectomy is suggested also for EGC. This
      study validated the effectiveness of minimally invasive technique in the
      management of gastric cancer.

PMID- 18342482
TI  - [Should personality disorders be treated?].
AB  - Personality disorders are mental diseases in their own right. Their common
      characteristic is their onset during adolescence or, at the latest, in early
      adulthood. Personality disorders are very diverse and range from neuroses to
      psychoses. Personality disorders spontaneously become chronic, but they are
      nonetheless accessible to treatment. Possible treatments include psychoanalytic
      and cognitive-behavioral psychotherapies and psychotropic medications.

PMID- 18342483
TI  - [Influenza incidence estimated with a rapid diagnostic test in critically ill
      patients with acute respiratory failure during the 2005 and 2006 winter flu
      epidemics].
AB  - OBJECTIVE: To estimate the incidence of influenza infection with a rapid
      diagnostic test in patients hospitalized in an intensive care unit (ICU) during
      the epidemic periods of two consecutive winters (2005-2006). METHODS: This study
      tested nasal aspirate of all patients admitted to the ICU for acute respiratory
      failure during the influenza epidemic period with the QuickVue influenza rapid
      diagnostic test. RESULTS: The study included 39 patients: 22 men and 17 women.
      Their mean age was 69.7+/-13 years, their mean SAPS II score 54+/-21, their mean
      length of stay 14.7+/-20 days, and 43.5% had been vaccinated against influenza.
      The mortality rate was 33.3% (n=13). Four patients (10.2%) had a positive
      QuickVue test and were considered to have influenza associated with their primary
      diagnosis: pneumococcal pneumonia, haemophilus pneumonia, acute bronchitis, and
      acute bronchitis with acute cardiogenic edema. These patients were older than
      those with a negative test (80+/-7 versus 68+/-13 years, p=0.02). Their SAPS II,
      length of stay and mortality rate did not differ statistically from those with
      negative results. Chronic heart failure (but not COPD or non-vaccination) was
      more frequent in these patients (p=0.01). DISCUSSION: Several published studies
      report a satisfactory specificity and sensitivity for QuickVue. With this test,
      we estimated the incidence of influenza in patients hospitalized in our ICU for
      acute respiratory failure during flu epidemics at around 10%, close to that
      reported in previous studies.

PMID- 18342484
TI  - [Treatment of psychiatric diseases: many recent evolutions].

PMID- 18342481
TI  - Triple play: promoting neurovascular longevity with nicotinamide, WNT, and
      erythropoietin in diabetes mellitus.
AB  - Oxidative stress is a principal pathway for the dysfunction and ultimate
      destruction of cells in the neuronal and vascular systems for several disease
      entities, not promoting the ravages of oxidative stress to any less of a degree
      than diabetes mellitus. Diabetes mellitus is increasing in incidence as a result
      of changes in human behavior that relate to diet and daily exercise and is
      predicted to affect almost 400 million individuals worldwide in another two
      decades. Furthermore, both type 1 and type 2 diabetes mellitus can lead to
      significant disability in the nervous and cardiovascular systems, such as
      cognitive loss and cardiac insufficiency. As a result, innovative strategies that
      directly target oxidative stress to preserve neuronal and vascular longevity
      could offer viable therapeutic options to diabetic patients in addition to more
      conventional treatments that are designed to control serum glucose levels. Here
      we discuss the novel application of nicotinamide, Wnt signaling, and
      erythropoietin that modulate cellular oxidative stress and offer significant
      promise for the prevention of diabetic complications in the nervous and vascular
      systems. Essential to this process is the precise focus upon diverse as well as
      common cellular pathways governed by nicotinamide, Wnt signaling, and
      erythropoietin to outline not only the potential benefits, but also the
      challenges and possible detriments of these therapies. In this way, new avenues
      of investigation can hopefully bypass toxic complications, or at the very least,
      avoid contraindications that may limit care and offer both safe and robust
      clinical treatment for patients.

PMID- 18342485
TI  - A mathematical model of the in vitro keratinocyte response to chromium and nickel
      exposure.
AB  - A mathematical model describing the main mechanistic processes involved in
      keratinocyte response to chromium and nickel has been developed and compared to
      experimental in vitro data. Accounting for the interactions between the metal
      ions and the keratinocytes, the law of mass action was used to generate ordinary
      differential equations which predict the time evolution and ion concentration
      dependency of keratinocyte viability, the amount of metal associated with the
      keratinocytes and the release of cytokines by the keratinocytes. Good agreement
      between model predictions and existing experimental data of these endpoints was
      observed, supporting the use of this model to explore physiochemical parameters
      that influence the toxicological response of keratinocytes to these two metals.

PMID- 18342486
TI  - The factor structure of Posttraumatic Stress Disorder symptoms among bereaved
      individuals: a confirmatory factor analysis study.
AB  - Posttraumatic Stress Disorder (PTSD) is defined in DSM-IV as an anxiety disorder
      that encompasses symptom-clusters of reexperiencing, avoidance, and hyperarousal.
      Several studies have examined the factor structure of PTSD symptoms. To our
      knowledge, no studies have yet examined the factor structure of loss-related PTSD
      symptoms in samples exclusively comprised of bereaved individuals. Such an
      examination is important because it can advance our understanding of the
      stability of the structure of PTSD symptoms across groups confronted with
      different aversive life-events and of processes underlying the occurrence of PTSD
      symptoms after loss. In this study, five alternative models of the factor
      structure of PTSD symptoms were examined in a sample of 347 mourners. Results
      showed that, in this group, PTSD symptoms are best conceptualized as forming four
      factors: reexperiencing, avoidance, dysphoria, and hyperarousal. Patterns of
      correlations with depression and complicated grief supported the validity of the
      model.

PMID- 18342487
TI  - A formal decision analysis identifies an optimal treatment strategy in a resource
      poor setting.
AB  - OBJECTIVE: Decision analytic techniques use formal specifications of utility for
      the four fundamental decision events: true positives, false positives, true
      negatives, and false negatives. An optimal policy is the one with the lowest
      expected net cost. In this paper, decision analytic techniques for treatment
      selection based on patient characteristics are applied to a resource-poor
      setting. STUDY DESIGN AND SETTING: A cohort of 986 female sex workers in
      Antananarivo and Tamatave, Madagascar were tested for cervical infection at
      baseline and again 2 months later after presumptive treatment for gonorrhea and
      chlamydia. RESULTS: Three equivalent approaches to identify the optimal policy
      based on patient characteristic subgroups are demonstrated. Two of them require
      exhaustive searches of all possible alternatives. The third identifies the
      optimal policy as an analytic expression that compares a decision function with a
      threshold and leads to a closed-form solution. With this approach, the optimal
      policy can be expressed in four equivalent forms using basic epidemiological
      measures: likelihood ratio, predicted probability of disease, logistic regression
      parameters, and total risk score. CONCLUSION: These methods illustrate the
      application of a decision analysis to clinical epidemiology. Management of
      cervical infection for sex workers in Madagascar occurs under severe resource
      constraints, and therefore requires an algorithm for identifying optimal
      treatment regimens.

PMID- 18342488
TI  - Feasibility and validity were demonstrated of an online case-control study using
      the prototype of recent-onset systemic lupus erythematosus.
AB  - OBJECTIVE: To test the feasibility and validity of the online case-control study
      design through the empirical deployment of a prototype study of recent-onset
      systemic lupus erythematosus (SLE). STUDY DESIGN AND SETTING: We conducted an
      Internet-based case-control study of SLE during 2003-2005. The source population
      comprised Google users searching on medical key terms, solicited using sponsored
      links. Cases fulfilled a self-administered algorithm for SLE diagnosed within 5
      years. A subset underwent confirmation by medical record review. Controls were
      matched to cases using a propensity score. RESULTS: Four hundred and two cases
      and 693 control applicants finished the questionnaires, yielding 389 matched case
      control pairs. Eighty-two percentage of the records documented a clinical
      diagnosis of SLE, and 61% documented >or=4 American College of Rheumatology
      criteria for SLE. Control applicants resembled Internet users, with the
      exceptions of comprising more women (86% vs. 52%) and fewer minority individuals
      (e.g., 5% vs. 9% for African-Americans). There was a broad representation of
      clinical manifestations. SLE was associated with miscarriage (odds ratio
      [OR]=3.0, 95% confidence interval [CI]=2.0-4.7), allergy to sulfonamides (OR=2.2,
      CI=1.5-3.2), hives (OR=1.9, CI=1.4-2.5), and shingles (OR=2.3, CI=1.4-3.7).
      CONCLUSION: It is possible to perform case-control studies over the Internet
      using an internally valid design, obtain reliable information from participants,
      and confirm established associations.

PMID- 18342489
TI  - Patients with systemic autoimmune diseases could not distinguish comorbidities
      from their index disease.
AB  - OBJECTIVE: To assess the construct validity of the Self-Administered Comorbidity
      Questionnaire (SCQ) in patients with systemic sclerosis (SSc) and systemic lupus
      erythematosus (SLE). METHODS: The SCQ was modified for the SSc cohort to
      emphasize the objective of recording problems other than the patients'
      scleroderma. It was administered to 406 SSc and 147 SLE patients. Construct
      validity of the SCQ was evaluated separately in the SSc and SLE cohorts by
      testing the hypotheses that a valid comorbidity index should correlate with age
      and health-related quality of life (Medical Outcomes Trust Short Form 36 [SF 36])
      but not with disease-specific variables. RESULTS: The SCQ score correlated with
      age in the SSc patients only (Tau B=0.37, P<0.001) and not in the SLE patients.
      It correlated with the SF 36 in both SSc and SLE. However, it also correlated
      with several disease-related variables. There was significant overlap between
      reports of comorbidities and disease-related problems in the SSc cohort.
      CONCLUSION: Patients with systemic autoimmune diseases cannot distinguish true
      comorbidities from conditions related to their index disease and, as such, a self
      administered comorbidity questionnaire does not appear useful in these diseases.

PMID- 18342490
TI  - How to do a safe tracheostomy.
AB  - A new technique of surgical tracheostomy is described. Prior to performing the
      tracheostomy, the endotracheal tube (ETT) is advanced further down the trachea so
      that the end of the tube is positioned just above the carina. Using the flexible
      endoscope within the ETT the positioning can be done with precision. This
      manoeuvre avoids the cuff of the ETT being perforated as it is well below the
      site of the tracheal window. Following the creation of an opening in the trachea,
      the patient continues to have a definitive airway. In this controlled
      environment, time is taken to obtain haemostasis at the tracheostomy site, place
      a rescue stitch and also suction above the cuff of the ETT. A study was carried
      out in a series of 15 patients by recording various measurements during the
      procedure to confirm the accuracy of this technique.

PMID- 18342491
TI  - Changes of visual evoked potential induced by lateral geniculate nucleus kindling
      in rats.
AB  - PURPOSE: The present study was undertaken to investigate the changes of visual
      evoked potential (VEP) induced by lateral geniculate nucleus (LGN) kindling in
      comparison with those induced by amygdala (AMG) and hippocampus (HPC) kindling in
      rats. METHODS: Under pentobarbital anesthesia, the rats were fixed to a
      stereotaxic apparatus, and stainless steel electrodes were implanted into the
      LGN, AMG, HPC and the occipital cortex (OCOR). Bipolar stimulation was applied to
      the LGN, AMG or HPC every day until generalized seizure was obtained. VEP was
      recorded from the OCOR before the first day of electric stimulation (pre-kindled)
      and after the development of kindling (post-kindled). RESULTS: After the
      development of LGN kindling, the amplitudes of early VEP components (P(1)-N(1)
      and N(1)-P(2)) were significantly augmented in comparison with those of pre
      kindled rats. In addition, the duration of the photically evoked after-discharge
      burst (duration of VEP) was significantly prolonged by LGN kindling. On the other
      hand, in AMG and HPC kindling, no significant changes were observed in VEP
      between pre-kindled and post-kindled rats. CONCLUSIONS: The changes of VEP
      observed in patients with photosensitive epilepsy are also demonstrated in animal
      study using LGN kindling.

PMID- 18342492
TI  - Community-associated methicillin-resistant Staphylococcus aureus (MRSA) in
      Australia.
AB  - A series of epidemics of community-associated methicillin-resistant
      Staphylococcus aureus (CA-MRSA) have occurred in Australia, starting in Western
      Australia in the early 1990s, in the Northern Territory soon thereafter and in
      eastern states in the mid 1990s. The Western Australian epidemic has been due
      mainly to Panton-Valentine leukocidin (PVL)-negative clones, whilst PVL-positive
      clones have predominated in the east. More recently, the major epidemic clones
      have spread throughout the country, whilst multiple new minor clones have
      emerged, mainly in Western Australia. A total of 45 clones of CA-MRSA have been
      detected in Australia to date: 30 of these carry SCCmec IV, 6 carry SCCmec V and
      9 carry novel SCCmec types. Overall, CA-MRSA clones have been associated
      predominantly with skin and soft-tissue infections. PVL-positive clones have been
      associated with furunculosis, necrotising pneumonia and osteomyelitis and have
      caused fatalities in otherwise healthy children and young adults. Initial
      treatment of these infections remains problematic, as it is frequently
      inappropriate. Of particular concern, healthcare-associated acquisition of CA
      MRSA clones is now increasing, although major hospital outbreaks have not
      occurred yet.

PMID- 18342493
TI  - Optimised NQR pulse technique for the effective detection of Heroin Base.
AB  - The nuclear quadrupole resonance (NQR) method has been applied to Heroin Base
      (HB) to find an optimised multi-pulse technique for effective detection of HB.
      Experimental results of applying the proposed spin-locking multi-pulse (SLMP)
      technique to nitrogen-14 NQR in this sample are presented and convincingly
      demonstrate as a path towards efficient detection. A detection using a sequence
      of this character could be achieved over real-world scan volumes for screening of
      goods. All experiments were carried out at room temperature.

PMID- 18342494
TI  - (51)V solid-state NMR investigations and DFT studies of model compounds for
      vanadium haloperoxidases.
AB  - Three cis-dioxovanadium(V) complexes with similar N-salicylidenehydrazide ligands
      modeling hydrogen bonding interactions of vanadate relevant for vanadium
      haloperoxidases are studied by (51)V solid-state NMR spectroscopy. Their
      parameters describing the quadrupolar and chemical shift anisotropy interactions
      (quadrupolar coupling constant C(Q), asymmetry of the quadrupolar tensor eta(Q),
      isotropic chemical shift delta(iso), chemical shift anisotropy delta(sigma),
      asymmetry of the chemical shift tensor eta(sigma) and the Euler angles alpha,
      beta and gamma) are determined both experimentally and theoretically using DFT
      methods. A comparative study of different methods to determine the NMR parameters
      by numerical simulation of the spectra is presented. Detailed theoretical
      investigations on the DFT level using various basis sets and structural models
      show that by useful choice of the methodology, the calculated parameters agree to
      the experimental ones in a very good manner.

PMID- 18342495
TI  - QDs-labeled microspheres for the adsorption of rabbit immunoglobulin G and
      fluoroimmunoassay.
AB  - This paper presents a study on the adsorption of rabbit immunoglobulin G onto
      CdTe quantum dots (QDs)/polystyrene microspheres. The adsorption appears to be
      sensitive to pH conditions and ionic strength. Maximum adsorption for protein was
      obtained near the isoelectric point. Adsorption isotherm analysis demonstrated
      that the electrostatic interaction plays an important role in the adsorption of
      protein. The thickness of adsorbed layer calculated from the maximal adsorption
      amounts (q(m)) is 6.5 nm, which indicates that the rabbit IgG molecules exist
      between the side-on and end-on mode in the monolayer. The bio-functional rabbit
      IgG/fluorescent microspheres were further used for the detection of antibody in
      fluoroimmunoassays. This approach allowed detection of goat anti-rabbit IgG in
      the range of 1-100 ng/mL.

PMID- 18342497
TI  - [Treatment of pediatric genital condyloma].
AB  - Condyloma, also known as venereal warts, are caused by human papillomavirus
      (HPV). Conventional wart therapies destroy infected keratinocytes rather than
      directly inhibiting viral infection or replication. No available drug therapy
      effectively eliminates HPV. Treatments are often disappointing for the patient,
      the family and the physician due to the duration of the disease and the frequency
      of recurrences in spite of treatment.

PMID- 18342498
TI  - Inhaled corticosteroids during pregnancy: a review of methodologic issues.
AB  - BACKGROUND: There is evidence in the literature that inhaled corticosteroids
      (ICSs) are safe for pregnant women with asthma and their infants. Although this
      is useful information about ICS use during pregnancy, some articles must be
      viewed cautiously because of lack of power and adjustment for potentially
      important confounding variables. OBJECTIVE: To summarize evidence on the
      potential effects of ICSs to treat asthma in pregnant mothers and their children
      with particular focus on study power. METHODS: Studies published before September
      1, 2007, and focusing mainly on ICS use for asthma treatment during pregnancy
      were researched in Pubmed and the Cochrane Library. Post hoc power calculations
      were completed using data reported in the published articles. RESULTS: Twenty
      three studies that evaluated the associations between ICS use during pregnancy
      and maternal and/or perinatal outcomes were retained. Only six studies on the
      association between ICS use and maternal outcomes reported significant results;
      five studies found significant associations between ICS use and perinatal
      outcomes. Regarding non-significant results, two studies on maternal outcomes and
      seven studies on perinatal outcomes had a power higher than 80% to detect a
      relative risk of 1.5 or a mean birth weight difference of 500 g. CONCLUSION:
      While there currently is some degree of evidence to support the safety of ICS use
      during pregnancy, this review highlights the limited statistical power of several
      studies published in this area.

PMID- 18342499
TI  - Epidermal Notch signalling: differentiation, cancer and adhesion.
AB  - The Notch pathway plays an important role in regulating epidermal
      differentiation. Notch ligands, receptors and effectors are expressed in a
      complex and dynamic pattern in embryonic and adult skin. Genetic ablation or
      activation of the pathway reveals that Notch signalling promotes differentiation
      of the hair follicle, sebaceous gland and interfollicular epidermal lineages and
      that Notch acts as an epidermal tumour suppressor. Notch signalling interacts
      with a range of other pathways to fulfil these functions and acts via RBP-Jkappa
      dependent and independent mechanisms. The effects on differentiation can be cell
      autonomous and non-autonomous, and Notch contributes to stem cell clustering via
      modulation of cell adhesion.

PMID- 18342500
TI  - Bortezomib-mediated proteasome inhibition as a potential strategy for the
      treatment of rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood,
      divided into two major histological subtypes, embryonal (ERMS) and alveolar
      (ARMS). To explore the possibility that the proteasome could be a target of
      therapeutic value in rhabdomyosarcoma, we treated several RMS cell lines with the
      proteasome inhibitor bortezomib (Velcade or PS-341) at a concentration of 13-26
      nM. RMS cells showed high sensitivity to the drug, whereas no toxic effect was
      observed in primary human myoblasts. In both ERMS and ARMS cells bortezomib
      promoted apoptosis, activation of caspase 3 and 7 and induced a dose-dependent
      reduction of anchorage-independent growth. Furthermore, bortezomib induced
      activation of the stress response, cell cycle arrest and the reduction of NF
      kappaB transcriptional activity. Finally, bortezomib decreased tumour growth and
      impaired cells viability, proliferation and angiogenesis in a xenograft model of
      RMS. In conclusion, our data indicate that bortezomib could represent a novel
      drug against RMS tumours.

PMID- 18342501
TI  - Dying with cancer, living well with advanced cancer.
AB  - INTRODUCTION: There are 1.7 million deaths from cancer in Europe each year and by
      2020 the World Health Organisation (WHO) estimates that, globally, more than 15
      million people will experience cancer and 10 million will die from it each year.
      Furthermore, as new therapies are developed, people are living longer with cancer
      than in the past, and the population with cancer will be older. MATERIALS AND
      METHODS: We used epidemiologically based needs assessment approaches to estimate
      the number of people in Europe with symptoms and problems, published data and
      reviews to appraise treatment options, issues of communication, family care,
      bereavement and socio-demographic factors affecting care, and a European survey
      to consider the types of services. In addition, we used systematic literature
      review data to appraise the effectiveness of services and factors affecting place
      of death. RESULTS: The quality of life of virtually all cancer patients with
      advanced disease is impaired by one or more symptoms, emotional, social,
      spiritual and communication concerns. Patients have a median of 11 symptoms. In
      Europe there are up to 1.6 million patients with pain each year, and in around
      one third of these it will be severe, requiring complex treatment. Almost an
      equal number are affected by fatigue, and more than 1 in 2 are affected by
      anxiety and/or depression, breathlessness, insomnia, nausea, constipation and/or
      anorexia. There is a complex interaction of factors affecting place of death-
      related to illness, the individual and environment--and although most people want
      to die at home, in most countries the majority of cancer patients die in
      hospital. In response to patient and family needs, systematic review shows the
      effectiveness of palliative care services. However, the distribution of services
      across Europe is inequitable. CONCLUSION: Palliative care is becoming
      increasingly recognised as a vital component of cancer care, but requires
      investment in research, education and services, incorporating appropriate needs
      assessment and outcome measurements.

PMID- 18342502
TI  - Treatment of childhood T-cell lymphoblastic lymphoma according to the strategy
      for acute lymphoblastic leukaemia, without radiotherapy: long term results of the
      EORTC CLG 58881 trial.
AB  - From June 1989 through to November 1998, 121 children with newly diagnosed T-cell
      lymphoblastic lymphoma (T-LBL) were included in the EORTC 58881 trial conducted
      by the Children's Leukaemia Group. The therapy regimen was based on a Berlin
      Frankfurt-Munster protocol, for a total duration of 24 months. Cranial
      irradiation, prophylactic cranial and local, was omitted, even for patients with
      central nervous involvement at diagnosis. In total, 119 patients were evaluable.
      The median follow-up was 6.7 years. The overall event-free survival (EFS) rate at
      6 years was 77.5% (standard error (SE)=4%). Median time of relapse was 1 year
      after complete remission (range 0.2-5.9 years). Only two (1.8%) patients had an
      isolated central nervous system relapse. For patients with complete response
      (n=16) to the 7-day prephase, the EFS rate at 6 years was 100% versus 14%
      (P<0.001) for patients with no response (n=7). Overall survival rate at 6 years
      was 86% (SE=3%). An intensive acute lymphoblastic leukaemia type chemotherapy
      regimen without irradiation leads to a high cure and survival rate in childhood T
      LBL without an increased CNS recurrence. This suggests that prophylactic cranial
      irradiation can safely be omitted. Response to the prephase appeared to be a
      strong prognostic factor for EFS.

PMID- 18342503
TI  - CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of
      gastric cancer in the European Prospective Investigation into Cancer and
      Nutrition (EPIC-EURGAST).
AB  - Despite declining incidence rates, gastric cancer (GC) is a major cause of death
      worldwide. E-Cadherin is an adhesion molecule that is thought to be involved in
      GC. Germline mutations in the E-Cadherin gene (CDH1) have been identified in
      hereditary diffuse GC. Also, a promoter polymorphism at position -160 C/A has
      been suggested to lead to transcriptional down regulation and has been shown to
      affect GC risk in some studies. However, very little information exists on the GC
      risk association of other CDH1 polymorphisms and it is unclear whether any
      associations may be different by GC anatomical sites or histological types. Thus,
      a case-control study (cases=245/controls=950) nested within the European
      Prospective Investigation into Cancer and Nutrition (EPIC) cohort was conducted
      to assess the GC risk association of eight CDH1 gene polymorphisms. None of the
      CDH1 polymorphisms or haplotypes analysed were associated with GC risk and no
      differences of effect were observed by Helicobacter pylori infection status.
      However, three CDH1 polymorphisms in the same haplotype block, including the CDH1
      160C/A, interacted with smoking to increase GC risk in smokers but not in never
      smokers. These findings should be confirmed in larger independent studies.

PMID- 18342504
TI  - The influence of the degree of cross-linking on the adsorption properties of
      chitosan beads.
AB  - The influence of the degree of cross-linking (DCL) on chitosan beads was studied.
      Chitosan was prepared from the exoskeleton of Cape rock-lobsters, collected from
      the surroundings of Cape Town, South Africa. The chitosan beads were
      characterized; the beads water contents and pKa varied in the range of 90-96% and
      4.3-6.0, respectively, and were found to decrease with increasing DCL (0.0
      34.0%). A pH-model, which described the reversibility of the metal adsorbed onto
      the beads, was used to predict the equilibrium properties of copper adsorption
      onto the cross-linked beads. The model accounts for the effect of pH and the
      important model parameters, the equilibrium adsorption constant (Kads) and to a
      lesser extent the adsorbent adsorption capacity (qmax) showed to decrease with
      the DCL. The adsorbent capacity and the adsorption constant were determined as
      3.8-5.0mmol/g chitosan and (9-90)x10(-4), respectively. The adsorption kinetics
      could be described using a shrinking core model and the effective diffusion
      coefficient (Deff) was determined as (8.0-25.8)x10(-11)m2/s. It was found that
      Deff decreases with the DCL mainly due to the decreased in water content of the
      beads at high DCL.

PMID- 18342505
TI  - Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory
      FMS inhibitors.
AB  - A series of pyrimidinopyridones has been designed, synthesized and shown to be
      potent and selective inhibitors of the FMS tyrosine kinase. Introduction of an
      amide substituent at the 6-position of the pyridone core resulted in a
      significant potency increase. Compound 24 effectively inhibited in vivo LPS
      induced TNF in mice greater than 80%.

PMID- 18342506
TI  - Synthesis of novel spiropyrrolizidines as potent antimicrobial agents for human
      and plant pathogens.
AB  - A series of novel dispirooxindolopyrrolizidine derivatives have been synthesized
      through 1,3-dipolar cycloaddition reaction of azomethine ylide generated from
      proline and isatin with the dipolarophile (E)-2-arylidine-1-keto carbazoles. The
      synthesized cycloadducts were evaluated for antimicrobial activities. Compounds
      7d and 7e showed relatively good antibacterial and antifungal activities.

PMID- 18342507
TI  - A visual sense of number.
AB  - Evidence exists for a nonverbal capacity for the apprehension of number, in
      humans [1] (including infants [2, 3]) and in other primates [4-6]. Here, we show
      that perceived numerosity is susceptible to adaptation, like primary visual
      properties of a scene, such as color, contrast, size, and speed. Apparent
      numerosity was decreased by adaptation to large numbers of dots and increased by
      adaptation to small numbers, the effect depending entirely on the numerosity of
      the adaptor, not on contrast, size, orientation, or pixel density, and occurring
      with very low adaptor contrasts. We suggest that the visual system has the
      capacity to estimate numerosity and that it is an independent primary visual
      property, not reducible to others like spatial frequency or density of texture
      [7].

PMID- 18342508
TI  - A simple vision-based algorithm for decision making in flying Drosophila.
AB  - Animals must quickly recognize objects in their environment and act accordingly.
      Previous studies indicate that looming visual objects trigger avoidance reflexes
      in many species [1-5]; however, such reflexes operate over a close range and
      might not detect a threatening stimulus at a safe distance. We analyzed how fruit
      flies (Drosophila melanogaster) respond to simple visual stimuli both in free
      flight and in a tethered-flight simulator. Whereas Drosophila, like many other
      insects, are attracted toward long vertical objects [6-10], we found that smaller
      visual stimuli elicit not weak attraction but rather strong repulsion. Because
      aversion to small spots depends on the vertical size of a moving object, and not
      on looming, it can function at a much greater distance than expansion-dependent
      reflexes. The opposing responses to long stripes and small spots reflect a simple
      but effective object classification system. Attraction toward long stripes would
      lead flies toward vegetative perches or feeding sites, whereas repulsion from
      small spots would help them avoid aerial predators or collisions with other
      insects. The motion of flying Drosophila depends on a balance of these two
      systems, providing a foundation for studying the neural basis of behavioral
      choice in a genetic model organism.

PMID- 18342509
TI  - Reproducibility of sagittal pelvic tilt measurements in normal subjects using
      digital inclinometry.
AB  - Standing sagittal pelvic tilt posture is widely assessed qualitatively, yet no
      efficient non-invasive quantitatively method is available for measuring pelvic
      tilt position or its amplitude. The main objective of the current study was to
      assess the intra- and inter-tester reproducibility of digital inclinometry-based
      (DI) measurements of pelvic tilt in healthy subjects. Pelvic inclination was
      measured while standing in neutral position (NP), maximal anterior pelvic tilt
      (APT) and maximal posterior pelvic tilt (PPT) which served for calculating the
      total pelvic tilt (TPT) range of motion (TPT=PPT-APT). On two separate test
      occasions two convenience samples of healthy women and men (N=15 in each) were
      each measured by two different testers. In both groups the intra-tester
      reproducibility indices of NP, APT, PPT and TPT were acceptable as revealed by
      high and significant ICCs and low standard error of measurements (SEM). In women
      the inter-tester reproducibility indices, of the same variables, were high as
      distinguished by no significant differences between testers and high and
      significant ICCs. In men, significant differences were found in APT and PPT but
      the between-testers TPT scores were similar. Collectively these findings indicate
      that pelvic inclinometry yields acceptable reproducibility which in the light of
      the facility of the method may render it an efficient clinical tool.

PMID- 18342510
TI  - Age-related changes in the rat hippocampus.
AB  - The human brain is uniquely powerful in its cognitive abilities, yet the
      hippocampal and neocortical circuits that mediate these complex functions are
      highly vulnerable during aging. In this study, we analyzed age-related changes in
      the rat hippocampus by studying newborn (1 month), middle-aged (12 months), and
      older (24 months) male and female Sprague-Dawley rats. We evaluated neuronal
      dystrophy, neuron scattering, and granulovacuolar degeneration in the hippocampal
      area using light microscopy, according to age and gender. We detected significant
      neuronal dystrophy in the CA1, CA2, and CA3 areas in male rats, and in the CA1,
      CA3, and CA4 areas in female rats. Degenerative changes, indicated by neuron
      scattering, were observed in the CA1, CA2, and CA3 areas of male and the CA2 and
      CA4 areas of female rats. Changes in all areas of the hippocampus were observed
      with increasing age; these changes included neuronal dystrophy and neuron
      scattering and did not differ significantly between male and female rats.

PMID- 18342511
TI  - Multiple infected cerebral hydatid cysts.
AB  - We report an unusual patient with multiple infected cerebral hydatid cysts. A 20
      year-old man presented with a 2-month history of headache and progressive left
      sided hempiparesis. A cerebral CT scan showed a large and heterogeneous parieto
      occipital lesion. During surgery an infected hydatid cyst was discovered with
      multiple daughter vesicles. Post-operatively the patient was treated with
      albendazol, cefotaxime and metronidazole. The clinical course was good with total
      recovery of the hemiparesis. A follow-up CT scan showed persistence of some small
      deep-seated cysts. Multiple infected cerebral hydatid cyst is uncommon and can be
      confused with other cystic brain lesions. The aim of surgery is to remove the
      cyst unruptured and this should be followed by antihelminthic and antibiotic
      treatment in order to avoid recurrences.

PMID- 18342512
TI  - In vivo evaluation of an episcleral multielectrode array for stimulation of the
      retina with reduced retinal ganglion cell mass.
AB  - A visual prosthesis is an experimental device designed to activate residual
      functional neurons in the visual pathway to generate artificial vision for blind
      patients. Specifically, for photoreceptor disease, a microelectrode array applied
      to the surface of the sclera could potentially serve to stimulate the remaining
      interneurons in the retina to produce topographically mapped visual percepts.
      However, of those neurons spared in the disease process, the retinal ganglion
      cells (RGC), which represent the final output neurons of the retina, can be
      markedly reduced in number. Using an albino rabbit model with RGC deficits, acute
      recording of cortical electrical evoked potential was performed to ascertain
      whether such a stimulation strategy is feasible. By analyzing the strength
      duration curve (current threshold vs. pulse duration) and cortical activation
      profiles, our results prove that bioelectrically safe and spatially
      differentiated stimulation of the retina is feasible notwithstanding the
      condition of markedly reduced RGC counts.

PMID- 18342513
TI  - Use of ventricular cerebrospinal fluid lactate measurement to diagnose
      cerebrospinal fluid infection in patients with intraventricular haemorrhage.
AB  - Early diagnosis of ventriculostomy-associated cerebrospinal fluid (CSF) infection
      in acute neurosurgical patients can be difficult. The use of prophylactic
      antibiotics in intraventricular or subarachnoid haemorrhage decreases the
      sensitivity of cell counts, Gram staining and bacterial culture as diagnostic
      tools. We prospectively collected clinical and cerebrospinal data for 16 patients
      with intraventricular haemorrhage, with an external ventricular drain inserted,
      with or without spontaneous subarachnoid haemorrhage. Three (18.8%) patients had
      cerebrospinal fluid infection, with appropriate changes in antibiotic regimens
      needed. All three patients had CSF lactate levels of >4 mmol/L (6.4 mmol/L, 7.8
      mmol/L, 7.9 mmol/L). Eleven out of 13 patients without CSF infection had CSF
      lactate levels of below 4 mmol/L. The two patients with CSF lactate levels of 4-6
      mmol/L were grade 5 subarachnoid haemorrhage patients, one with renal impairment.
      Using a cut-off lactate level of 4 mmol/L, the positive predictive value was 60%
      and negative predictive value was 100% for CSF infection. A CSF lactate level of
      above 4 mmol/L should prompt suspicion of CSF infection in intraventricular
      haemorrhage patients with an external ventricular drain.

PMID- 18342514
TI  - Primary Ewing's sarcoma of the petroclival bone.
AB  - A 17-year-old male presented with signs of raised intracranial tension and
      multiple cranial nerve dysfunction. Radiological imaging revealed an extradural
      calcified tumor involving the right petrous bone and adjacent clivus. The patient
      underwent extensive surgical debulking of the mass. Histopathological study
      revealed that the tumor was Ewing's sarcoma. Post-operative radio- and
      chemotherapy were administered. The patient's cranial nerve dysfunctions had
      recovered to some extend at 12 months' follow-up. Ewing's sarcoma arising from
      the skull base is an extremely rare lesion. The relevant literature on the
      subject is reviewed.

PMID- 18342515
TI  - Features of stabbing, cough, exertional and sexual headaches in a Turkish
      population of headache patients.
AB  - The aim of this study was to determine the features and prevalence of primary
      stabbing headache, primary exertional headache, primary headache associated with
      sexual activity, and primary cough headache in a Turkish population of headache
      patients. The data for this study were obtained from 245 patients with headache.
      Of these patients, 55 fulfilled the International Classification of Headache
      Disorders (second edition) diagnostic criteria for 'other primary headaches' such
      as primary stabbing headache (n=31), primary cough headache (n=1), primary
      exertional headache (n=13), primary headache associated with sexual activity
      (n=4), and both primary cough headache and primary exertional headache (n=6).
      Primary stabbing headache was found in 12.6% of patients, primary cough headache
      in 0.4%, primary exertional headache in 5.3% and primary headache associated with
      sexual activity in 1.6%.

PMID- 18342516
TI  - Spontaneous involution of two sinus pericranii - a unique case and review of the
      literature.
AB  - Sinus pericranii is a rare vascular anomaly in which an abnormal communication
      exists between the extracranial venous system and the dural venous sinuses. The
      natural history is of increasing size and potential life-threatening
      complications, including thrombosis and haemorrhage. Thus surgical management is
      the mainstay of treatment. We present a unique case of spontaneous involution of
      two sinus pericranii in a 1-year-old patient, the second reported case of
      spontaneous involution in the literature, and the first in which regression
      occurred at such a young age. The clinical, diagnostic and management options are
      discussed.

PMID- 18342517
TI  - Investigating biological activity spectrum for novel quinoline analogues 2:
      hydroxyquinolinecarboxamides with photosynthesis-inhibiting activity.
AB  - Two series of amides based on quinoline scaffold were designed and synthesized in
      search of photosynthesis inhibitors. The compounds were tested for their
      photosynthesis-inhibiting activity against Spinacia oleracea L. and Chlorella
      vulgaris Beij. The compounds lipophilicity was determined by the RP-HPLC method.
      Several compounds showed biological activity similar or even higher than that of
      the standard (DCMU). The structure-activity relationships are discussed.

PMID- 18342518
TI  - Novel 5-azaindolocarbazoles as cytotoxic agents and Chk1 inhibitors.
AB  - We describe here an efficient synthesis of new 5-azaindolocarbazoles designed for
      cytotoxic and Chk1 inhibiting properties. The synthesis of 'symmetrical' and
      'dissymmetrical' structures is discussed. Concerning the dissymmetrical 5
      azaindolocarbazoles derivatives, with both an indole moiety and a 5-azaindole
      moiety, the synthesis was achieved using two very efficient key steps. The first
      one is a Stille reaction with a 3-trimethylstannyl-5-azaindole derivative and the
      second one a photochemical step leading to the proposed polycyclic structure.
      Various pharmacomodulations were performed to investigate the structure-activity
      relationships (SAR). Several substituents such as OBn, OH, and methylenedioxy
      groups were successfully introduced on the indole moiety of the 5
      azaindolocarbazole. Compounds with or without substituents on the nitrogen atom
      of the maleimide were prepared, as well as derivatives with glucopyranosyl
      substituent on the nitrogen atom of the indole moiety. The cytotoxicity of these
      new compounds was evaluated on two cell lines (L1210, HT29). Several compounds
      showed cytotoxicity in the sub-micromolar range. Among the most cytototoxic was
      the 1,3-dioxolo[4,5-b]-6-(2-dimethylaminoethyl)-1H-pyrido[3',4':4,5]pyrrolo[3,2
      i]pyrrolo[3,4-g]carbazole-5,7(6H,12H)-dione (35, IC(50)=195 nM on L1210). The
      compounds were also investigated for their Chk1 inhibiting activity. Compounds
      without any substitution on the maleimide moiety were the most potent. This is
      the case of compounds 45-47 with IC(50) of, respectively, 72, 27, and 14nM toward
      Chk1. Compound 46, which exhibits moderate cytotoxicity, appears to be a good
      candidate for development in a multi-drug anticancer therapy.

PMID- 18342519
TI  - Computational modeling study of functional microdomains in cannabinoid receptor
      type 1.
AB  - The seven transmembrane helices (TMH) G-protein-coupled receptors (GPCRs)
      constitute one of the largest superfamily of signaling proteins found in mammals.
      Some of its members, in which the cannabinoid (CB) receptors are included, stand
      out because their functional states can be modulated by a broad spectrum of
      effector molecules. The relative ligand promiscuity exhibited by these receptors
      could be related with particular attributes conferred by their molecular
      architecture and represents a motivating issue to be explored. In this regard,
      this study represents an effort to investigate the cannabinoid receptor type 1
      (CB1) ligand recognition plasticity, using comparative modeling, molecular
      dynamics (MD) simulations and docking. Our results suggest that a cooperative set
      of subtle structural rearrangements within the TMHs provide to the CB1 protein
      the plasticity to reach alternate configurations. These changes include the
      relaxation of intramolecular constraints, the rotations, translations and kinks
      of the majority of TMHs and the reorganization of the ligand binding cavities.

PMID- 18342520
TI  - Cytogenetics of four species of Spirostreptidae (Diplopoda, Spirostreptida).
AB  - Considering an estimated number of millipedes of approximately 80,000,
      cytogenetic studies on these animals are rare, as only a total of 70 species have
      their karyotypes described. The present study reports on the chromosomal number
      of four Brazilian diplopods of the family Spirostreptidae: Urostreptus
      atrobrunneus with 2n=24, XY; Gymnostreptus olivaceus 2n=12, XY and Alloporus
      araraquarensis and A. principes, 2n=18, XY. The C-banding pattern and NOR
      staining of U. atrobrunneus, G. olivaceus and A. araraquarensis are described.

PMID- 18342521
TI  - Standardization of (125)I by the coincidence method and practical applications.
AB  - A new coincidence system, based on two thin NaI(Tl) crystals, 50 x 2mm(2), with
      beryllium windows, 1.5mgcm(-2), positioned approximately symmetrically from the
      source holder (at various distances) was constructed. The electronic chains of a
      classical 4piPC-gamma system were utilized. A multichannel analyzer was employed
      for energy calibration, and an oscilloscope for visualization of the pulses.
      After calibration, the system was used for the standardization of an (125)I
      solution. An energy window of 12-95keV containing the entire spectrum (single and
      sum peak) was employed, and a simple demonstration of Taylor's equation [1967. X
      ray-X-ray coincidence counting methods for the standardization of (125)I and
      (197)Hg. In: Standardization of Radionuclides: Proceedings of a International
      Atomic Energy Agency Symposium, Vienna, 1966, pp. 341-353, SM-79/65] for whole
      spectrum counting, was developed. The method and system were tested during the
      calibration of a LKB 2104 multi-gamma counter, by comparing the detection
      efficiency values obtained for this prepared standard solution and that utilized
      in the CIPM-CCRI(II) key comparison. The efficiency of the equipment was
      calculated as the mean of the two individual values. The result validates the
      method and demonstrates the accomplishment of the national traceability assurance
      in nuclear medicine for (125)I.

PMID- 18342522
TI  - On the use of mercury as a means of locating background sources in ultra low
      background HPGe-detector systems.
AB  - In low-level gamma-ray spectrometry, it is common to measure large samples in
      order to obtain low detection limits for the massic activity (in mBq/kg). These
      samples have significant shielding effects. In order to study whether the
      background sources in three ultra low-background HPGe detectors were located in
      the detector or in the shield, Marinelli beakers filled with hyperpure mercury
      were measured. Although the measurements were hampered by the presence of
      cosmogenically produced (194)Hg, information regarding the major background
      location of (40)K, (60)Co, (137)Cs, (210)Pb, (226)Ra, (228)Ra and (228)Th could
      be obtained.

PMID- 18342523
TI  - Defined solid-angle counter with variable geometry.
AB  - We describe a defined solid-angle counter for the standardization of radioactive
      sources of alpha-particle emitters. It has been built with the aim of combining
      good counting efficiencies, low uncertainties and flexibility of operation. The
      distance between source and detector can be changed in a continuous way with a
      precision guide and a ball screw from 8 to 19cm, which correspond to counting
      efficiencies between 0.023 and 0.004 for small size sources. A linear encoder
      allows the accurate determination of the source position. Alpha spectra of the
      sources are measured with an implanted silicon detector with an active area of
      2000mm(2). Uncertainties, excluding counting statistics, are below 0.1%.

PMID- 18342524
TI  - Liquid-scintillation-based anticoincidence counting of Co-60 and Pb-210.
AB  - The method of liquid-scintillation-based 4pibeta-gamma anticoincidence counting
      was employed to assay the radioactivity concentration of acid solutions
      containing radionuclides (60)Co and (210)Pb (in equilibrium with its daughters).
      The limiting factors on the accuracy for such activity measurements and
      suggestions for minimizing such factors are reported.

PMID- 18342525
TI  - Numerical analysis of alpha spectra using two different codes.
AB  - This work presents an intercomparison between commercial software for alpha
      particle spectrometry, Genie 2000, and the new free available software, Winalpha,
      developed by International Atomic Energy Agency (IAEA). In order to compare both
      codes, different environmental spectra containing plutonium, uranium, thorium and
      polonium have been analyzed, together with IAEA test alpha spectra. A statistical
      study was performed in order to evaluate the precision and accuracy in the
      analyses, and to enhance the confidence in using the software on alpha
      spectrometric studies.

PMID- 18342526
TI  - Standardization of (55)Fe by tracing method.
AB  - This work describes the procedure followed by the Laboratorio de Metrologia
      Nuclear (LMN) for the standardization of (55)Fe by the tracing method. This
      technique was applied using two radionuclides, which decay by the electron
      capture process followed by a prompt gamma-ray, namely (51)Cr and (54)Mn, as
      tracers. The calibration was performed in a 4pibeta-gamma coincidence system. The
      efficiency was obtained by selecting a gamma-ray window set at the 320keV total
      absorption peak for (51)Cr and at 834keV for (54)Mn.

PMID- 18342527
TI  - Pattern of axonal injury in murine myelin oligodendrocyte glycoprotein induced
      experimental autoimmune encephalomyelitis: implications for multiple sclerosis.
AB  - Axonal damage is a correlate for increasing disability in multiple sclerosis.
      Animal models such as experimental autoimmune encephalomyelitis (EAE) may help to
      develop better therapeutical neuroprotective strategies for the human disease.
      Here we investigate the pattern of axonal injury in murine myelin oligodendrocyte
      glycoprotein peptide 35-55 (MOG) induced EAE. Inflammatory infiltration, axonal
      densities and expression of amyloid precursor protein (APP), neurofilaments
      (SMI31 and 32) as well as expression of sodium channels were quantified in
      lesions, the perilesional area and normal appearing white matter (NAWM).
      Quantification of T cells and macrophages revealed a significant reduction of
      inflammatory infiltration at later disease stages despite an increase of
      demyelinated areas and persistent clinical disability. In lesions, axonal density
      was already significantly reduced early and throughout all investigated disease
      stages. A significant axonal loss was also seen in the grey matter and at later
      time points in the perilesion as well as NAWM. Numbers of axons characterized by
      non-phosphorylated neurofilaments and re-distribution of sodium channels 1.2 and
      1.6 increased over the course of MOG-EAE whilst APP positive axons peaked at the
      maximum of disease. Finally, double-labeling experiments revealed a strong
      colocalization of sodium channels with APP, neurofilaments and the axonal nodal
      protein Caspr, but not glial and myelin markers in actively demyelinating
      lesions. In summary, progressive axonal loss distant from lesions is mainly
      associated with changes in neurofilament phosphorylation, re-distribution of
      sodium channels and demyelination. This axonal loss is dissociated from acute
      inflammatory infiltration and markedly correlates with clinical impairment.
      Consequently, therapeutic intervention may be promising at early stages of EAE
      focusing on inflammation, or later in disease targeting degenerative mechanisms.

PMID- 18342528
TI  - Accuracy and survival of repeat mediastinoscopy after induction therapy for non
      small cell lung cancer in a combined series of 104 patients.
AB  - OBJECTIVE: Precise restaging of non-small cell lung cancer after induction
      therapy is of utmost importance. Remediastinoscopy remains a controversial
      procedure. In a combined, updated series of two thoracic centres, accuracy and
      survival of remediastinoscopy were determined. METHODS: From November 1994 to
      August 2005, remediastinoscopy was performed in 104 patients (98 men, 6 women)
      after induction therapy for locally advanced non-small cell lung cancer. Mean age
      was 64.3 years (range 38-85). Neoadjuvant chemotherapy was given in 79 patients
      and chemoradiotherapy in 25. Follow-up data were completed in January 2007.
      RESULTS: Remediastinoscopy was technically feasible in all patients except for
      one who died due to perioperative haemorrhage. Remediastinoscopy was positive in
      40 patients and negative in 64; the latter group underwent thoracotomy. There
      were 17 false-negative remediastinoscopies. Sensitivity of remediastinoscopy was
      71%, specificity 100% and accuracy 84%. Follow-up was complete for all patients.
      Sixty-nine died, mostly of distant metastases. Median survival time for the whole
      group was 18 months (95% confidence interval 11-25). Median survival time in
      patients with a positive remediastinoscopy was 14 months (95% confidence interval
      8-20), with a negative remediastinoscopy 28 months (95% confidence interval 15
      41) and with a false-negative remediastinoscopy 24 months (95% confidence
      interval 3-45). In univariate analysis the difference between positive and
      negative remediastinoscopies was highly significant (p=0.001). In a multivariate
      analysis including sex, age, histology, centre, and nodal status at
      remediastinoscopy, only nodal status was a significant independent prognostic
      factor (p=0.008). CONCLUSIONS: Remediastinoscopy is a valuable restaging
      procedure after induction therapy. Persisting mediastinal nodal involvement
      proven at remediastinoscopy heralds a poor prognosis.

PMID- 18342529
TI  - The place of excision repair cross complementation 1 (ERCC1) in surgically
      treated non-small cell lung cancer.
AB  - Platinum-based regimens are the cornerstones of therapy in adjuvant and
      neoadjuvant management of early stage non-small cell lung cancer (NSCLC).
      However, the survival benefit associated with platinum-based chemotherapy is
      marginal and therefore adequate patient selection is essential. Excision repair
      cross complementation 1 (ERCC1) is a key-enzyme in the repair of platinum-DNA
      adducts that has been demonstrated to influence the response to platinum-based
      therapy. We performed a systematic review of the literature from 1996 to
      September 2007 on studies that assessed the role of ERCC1 in resected NSCLC.
      Overall, nine studies were identified. ERCC1 expression has been assessed by mRNA
      expression (n=5) and/or by protein expression (immunohistochemistry) (n=5). One
      study assessed ERCC1 status by both methods. In these studies, patients with
      early stage NSCLC treated by surgery alone survived longer if ERCC1 levels are
      high (favourable prognostic value of high ERCC1 level). Conversely, patients
      treated by surgery and who receive chemotherapy, either as adjuvant therapy or
      for disease relapse, have a better overall survival when ERCC1 levels are low
      (favourable predictive value of low ERCC1 level). ERCC1 expression might assist
      in selecting patients who will respond to adjuvant (neoadjuvant) platinum-based
      chemotherapy. However, further investigation is necessary in order to
      prospectively confirm these results and to ascertain the most appropriate method
      of assessment. Thoracic surgeons should participate in this field of research.

PMID- 18342530
TI  - Factors affecting early and long-term outcomes after completion pneumonectomy.
AB  - OBJECTIVE: To identify factors that affect operative mortality and morbidity and
      long-term survival after completion pneumonectomy. METHODS: We retrospectively
      reviewed the charts of consecutive patients who underwent completion
      pneumonectomy at our cardiothoracic surgery department from January 1996 to
      December 2005. RESULTS: We identified 69 patients, who accounted for 17.8% of all
      pneumonectomies during the study period; 22 had benign disease and 47 malignant
      disease (second primary lung cancer, n=19; local recurrence, n=17; or metastasis,
      n=11). There were 50 males and 19 females with a mean age of 60 years (range, 29
      80 years). Postoperative mortality was 12% and postoperative morbidity 41%.
      Factors associated with postoperative mortality included obesity (p=0.005),
      coronary artery disease (p=0.03), removal of the right lung (p=0.02), advanced
      age (p=0.02), and renal failure (p<0.0001). Preoperative renal failure was the
      only significant risk factor for mortality by multivariate analysis (p=0.036).
      Bronchopleural fistula developed in seven patients (10%), with risk factors being
      removal of the right lung (p=0.04) and mechanical stump closure (p=0.03). Overall
      survival was 65% after 3 years and 46% after 5 years. Long-term survival was not
      affected by the reason for completion pneumonectomy. CONCLUSION: Although long
      term survival was acceptable, postoperative mortality and morbidity rates
      remained high, confirming the reputation of completion pneumonectomy as a
      challenging procedure. Significant comorbidities and removal of the right lung
      were the main risk factors for postoperative mortality. Improved patient
      selection and better management of preoperative renal failure may improve the
      postoperative outcomes of this procedure, which offers a chance for prolonged
      survival.

PMID- 18342531
TI  - Cardiothoracic surgery: time for reappraisal!

PMID- 18342532
TI  - Indications and outcome of salvage surgery for oesophageal cancer.
AB  - OBJECTIVE: Some patients with localised oesophageal cancer are treated with
      definitive chemoradiotherapy (CRT) rather than surgery. A subset of these
      patients experiences local failure, relapse or treatment-related complication
      without distant metastases, with no other curative treatment option but salvage
      oesophagectomy. The aim of this study was to assess the benefit/risk ratio of
      surgery in such context. METHODS: Review of a single institution experience with
      24 patients: 18 men and 6 women, with a mean age of 59 years (+/-9). Histology
      was squamous cell carcinoma in 18 cases and adenocarcinoma in 6. Initial stages
      were cIIA (n=5), cIIB (n=1) and cIII (n=18). CRT consisted of 2-6 sessions of the
      association 5-fluorouracil/cisplatin concomitantly with a 50-75 Gy radiation
      therapy. Salvage oesophagectomy was considered for the following reasons: relapse
      of the disease with conclusive (n=11) or inconclusive biopsies (n=7), intractable
      stenosis (n=3), and perforation or severe oesophagitis (n=3), at a mean delay of
      74 days (14-240 days) following completion of CRT. RESULTS: All patients
      underwent a transthoracic en-bloc oesophagectomy with 2-field lymphadenectomy.
      Thirty-day and 90-day mortality rates were 21% and 25%, respectively. Anastomotic
      leakage (p=0.05), cardiac failure (p=0.05), length of stay (p=0.03) and the
      number of packed red blood cells (p=0.02) were more frequent in patients who
      received more than 55 Gy, leading to a doubled in-hospital mortality when
      compared to that of patients having received lower doses. A R0 resection was
      achieved in 21 patients (87.5%). A complete pathological response (ypT0N0) was
      observed in 3 patients (12.5%). Overall and disease-free 5-year survival rates
      were 35% and 21%, respectively. There was no long-term survivor following R1-R2
      resections. Functional results were good in more than 80% of the long-term
      survivors. CONCLUSION: Salvage surgery is a highly invasive and morbid operation
      after a volume dose of radiation exceeding 55 Gy. The indication must be
      carefully considered, with care taken to avoid incomplete resections. Given that
      long-term survival with a fair quality of life can be achieved, such high-risk
      surgery should be considered in selected patients at an experienced centre.

PMID- 18342533
TI  - Is video-assisted thoracoscopic surgery a feasible approach for clinical N0 and
      postoperatively pathological N2 non-small cell lung cancer?
AB  - OBJECTIVE: It remains controversial whether video-assisted thoracoscopic surgery
      (VATS) major pulmonary resection (VMPR) with systematic node dissection (SND) is
      a feasible approach for clinical N0 and pathological N2 non-small cell lung
      cancer (cN0-pN2 NSCLC). We compared the clinical outcome of patients who
      underwent VMPR with SND for cN0-pN2 NSCLC with the outcome of patients who
      underwent MPR with SND by thoracotomy. We conducted this study to determine the
      feasibility of VMPR for cN0 and pN2 NSCLC patients and intraoperative node
      staging by node sampling. METHODS: Between 1997 and 2006, 770 patients underwent
      MPR with SND for NSCLC, wherein 450 patients had VMPR and 320 were subjected to
      open thoracotomy. There were 673 clinical N0 patients. Among them, we
      retrospectively reviewed 69 patients (10.3%) with cN0-pN2 NSCLC of which the
      greatest tumor dimension ranged from 20 to 50mm. These patients were divided into
      two groups: 37 patients under group V, who underwent VMPR, and 32 patients under
      group T, who underwent MPR by thoracotomy, for cN0-pN2 NSCLC. The majority of the
      patients underwent postoperative chemotherapy. RESULTS: There were no differences
      between the two groups regarding preoperative data or the number of nodes
      dissected. The rate of nodal metastasis (number of metastatic nodes/number of
      dissected nodes) was similar between the two groups (group V vs group T, 0.24 vs
      0.24 in total nodes dissected, 0.24 vs 0.23 in mediastinal nodes dissected). The
      3-year and 5-year recurrence-free survivals were similar (60.9% vs 49.6% and
      60.9% vs 49.6%), as well. Most of the pattern of recurrence was due to remote
      metastasis. In like manner, the 3-year and 5-year survivals were similar (67.6%
      vs 57.7% and 45.4% vs 41.1%). CONCLUSIONS: This study demonstrates that VMPR with
      SND is a feasible surgical therapy for cN0-pN2 NSCLC without loss of curability.
      It is unnecessary to convert the VATS approach to thoracotomy in order to do SND
      even if pN2 disease is revealed during VMPR.

PMID- 18342534
TI  - Hypericin phototoxicity induces different modes of cell death in melanoma and
      human skin cells.
AB  - Hypericin, the major component of St. John's Wort, absorbs light in the UV and
      visible ranges whereupon it becomes phototoxic through the production of reactive
      oxygen species. Although photodynamic mechanisms (i.e. through endogenous
      photosensitizers) play a role in UVA phototherapy for the treatment of skin
      disorders such as eczema and psoriasis, photodynamic therapy employing exogenous
      photosensitizers are currently being used only for the treatment of certain forms
      of non-melanoma skin cancers and actinic keratoses. There are few reports however
      on its use in treating melanomas. This in vitro study analyses the phototoxic
      effect of UVA (400-315 nm) - activated hypericin in human pigmented and
      unpigmented melanomas and immortalised keratinocytes and melanocytes. We show
      that neither hypericin exposure nor UV irradiation alone reduces cell viability.
      We show that an exposure to 1 microM UVA-activated hypericin does not bring about
      cell death, while 3 microM activated hypericin induces a necrotic mode of cell
      death in pigmented melanoma cells and melanocytes and an apoptotic mode of cell
      death in non-pigmented melanoma cells and keratinocytes. We hypothesis that the
      necrotic mode of cell death in the pigmented cells is possibly related to the
      presence of melanin-containing melanosomes in these cells and that the hypericin
      induced increase in reactive oxygen species leads to an increase in permeability
      of melanosomes. This would result in toxic melanin precursors (of an indolic and
      phenolic nature) leaking into the cytoplasm which in turn leads to cell death.
      Hypericin localisation in the endoplasmic reticulum in these cells shown by
      fluorescent microscopy, further support a disruption in cellular processing and
      induction of cell death. In contrast, this study shows that cells that do not
      contain melanosomes (non-pigmented melanoma cells and keratinocytes) die by
      apoptosis. Further, using a mitochondrial-specific fluorescent dye, we show that
      intracellular accumulation of hypericin induces a mitochondrial-associated
      caspase-dependent apoptotic mode of cell death. This work suggests that UVA is
      effective in activating hypericin and that this phototoxicity may be considered
      as treatment option in some cases of lentigo maligna or lentigo maligna melanoma
      that are too large for surgical resection.

PMID- 18342535
TI  - Meningioma.
AB  - Meningiomas are mostly benign tumours originating from the arachnoid cap cells,
      represent 13-26% of all intracranial tumours. They are more common in older age
      and in females. Deletion in NF2 gene and exposure to ionizing radiation are
      established risk factors, while the role of sex hormones is yet not clarified.
      Five-year survival for typical meningiomas exceeds 80%, but is poorer (5-year
      survival <60%) in malignant and atypical meningiomas. Papillary and
      haemangiopericytic morphology, large tumour size, high mitotic index, absence of
      progesterone receptors, deletions and loss of heterozygosity are poor prognostic
      factors. Complete surgical excision is the standard treatment. Radiotherapy is
      currently used in the clinical practice in atypical, malignant or recurrent
      meningioma at a total dose of 45-60Gy. However, the role of adjuvant irradiation
      is still controversial and has to be compared in a randomised prospective setting
      with a policy of watchful waiting. Radiosurgery has gained more and more
      importance in the management of meningiomas, especially in meningiomas that
      cannot be completely resected as for many skull base meningiomas. Medical therapy
      for patients with recurrent, progressive and symptomatic disease after repeated
      surgery, radiosurgery and radiotherapy is investigational. Hormonal therapy with
      progesterone antagonists has shown modest results, while chemotherapy with
      hydroxyurea appears moderately active.

PMID- 18342536
TI  - New therapies for ovarian cancer: cytotoxics and molecularly targeted agents.
AB  - Ovarian cancer, although a chemo-sensitive disease, is associated with high
      morbidity and mortality due to its often-late presentation. Platinums and taxanes
      have improved the prognosis over recent years but median overall survival is
      still unacceptably low (24-60 months). Apart from the manipulation of doses,
      schedules, mode of delivery, and combinations of existing drugs, new cytotoxics
      and molecularly targeted agents with different mechanisms of action must be
      evaluated in this patient population. This article will review the most recent
      clinical trials data pertaining to these new cytotoxic drugs including
      patupilone, telcyta, and trabectedin, as well as those of small molecules and
      inhibitors of the EGFR and VEGF receptor families. It will also discuss other
      potential signal transduction targets worthy of further evaluation in future
      trials.

PMID- 18342537
TI  - IL-4-induced Stat6 activities affect apoptosis and gene expression in breast
      cancer cells.
AB  - IL-4-induced Stat6 signaling is active in a variety of cell types, including
      immune cells and cancer cells, and plays an important role in the regulation of
      gene expression. Using EMSA gel shift assay and an antibody to Stat6, we
      phenotyped two breast cancer cell lines, ZR-75-1 being active Stat6(high)
      phenotype and BT-20 being defective Stat6(null) phenotype, respectively. Breast
      cancer cells carrying Stat6(null) phenotype exhibited increased spontaneous
      apoptosis compared with those carrying Stat6(high) phenotype. Expression
      microarray analyses demonstrated that IL-4 upregulated CCL26, SOCS1, CISH, EGLN3,
      and SIDT1, and downregulated DUSP1, FOS, and FOSB, respectively, in these breast
      cancer cells. Among those genes, CCL26 and SOCS1 were known genes regulated by IL
      4/Stat6 pathway, but CISH, EGLN3, SIDT1, DUSP1, FOS, and FOSB were novel genes
      demonstrated to be IL-4 responsive for the first time. IL-4 also upregulated 38
      genes unique to Stat6(null) BT-20 cells and 23 genes unique to Stat6(high) ZR-75
      1 cells, respectively. Furthermore, Stat6(high) and Stat6(null) cells showed very
      different profiles of constitutively expressed genes relevant to apoptosis and
      metastasis among others, which serve as a valuable expression database and
      warrant for detailed studies of IL-4/Stat6 pathway in breast cancer.

PMID- 18342538
TI  - Purification of GFP fusion proteins with high purity and yield by monoclonal
      antibody-coupled affinity column chromatography.
AB  - GFP has often been used as a marker of gene expression, protein localization in
      living and fixed tissues as well as for protein targeting in intact cells and
      organisms. Monitoring foreign protein expression via GFP fusion is also very
      appealing for bioprocess applications. Many cells, including bacterial, fungal,
      plant, insect and mammalian cells, can express recombinant GFP (rGFP)
      efficiently. Several methods and procedures have been developed to purify the
      rGFP or recombinant proteins fused with GFP tag. However, most current GFP
      purification methods are limited by poor yields and low purity. In the current
      study, we developed an improved purification method, utilizing a FMU-GFP.5
      monoclonal antibody (mAb) to GFP together with a mAb-coupled affinity
      chromatography column. The method resulted in a sample that was highly pure (more
      than 97% homogeneity) and had a sample yield of about 90%. Moreover, the GFP
      epitope permitted the isolation of almost all the active recombinant target
      proteins fused with GFP, directly and easily, from the crude cellular sources.
      Our data suggests this method is more efficient than any currently available
      method for purification of GFP protein.

PMID- 18342539
TI  - Fifty years of coiled-coils and alpha-helical bundles: a close relationship
      between sequence and structure.
AB  - alpha-Helical coiled coils are remarkable for the diversity of related
      conformations that they adopt in both fibrous and globular proteins, and for the
      range of functions that they exhibit. The coiled coils are based on a heptad (7
      residue), hendecad (11-residue) or a related quasi-repeat of apolar residues in
      the sequences of the alpha-helical regions involved. Most of these, however,
      display one or more sequence discontinuities known as stutters or stammers. The
      resulting coiled coils vary in length, in the number of chains participating, in
      the relative polarity of the contributing alpha-helical regions (parallel or
      antiparallel), and in the pitch length and handedness of the supercoil (left- or
      right-handed). Functionally, the concept that a coiled coil can act only as a
      static rod is no longer valid, and the range of roles that these structures have
      now been shown to exhibit has expanded rapidly in recent years. An important
      development has been the recognition that the delightful simplicity that exists
      between sequence and structure, and between structure and function, allows coiled
      coils with specialized features to be designed de novo.

PMID- 18342540
TI  - The cortical motor threshold reflects microstructural properties of cerebral
      white matter.
AB  - Transcranial magnetic stimulation (TMS) can be used to probe distinct aspects of
      excitability of the primary motor hand area (M1(Hand)). The motor threshold (MT)
      reflects the trans-synaptic excitability of corticospinal output neurons. The MT
      corresponds to the minimal intensity at which TMS evokes a contralateral motor
      response. Here, we employed diffusion-weighted imaging (DWI) to examine whether
      inter-individual differences in MT of the left and right M1(Hand), an index of
      cortical excitability, are associated with variations in fractional anisotropy
      (FA), an index of white matter microstructure. Resting and active MT showed an
      inverse linear relationship with regional FA values in large bihemispheric
      clusters, including the white matter underlying primary motor, premotor and
      posterior prefrontal cortices, as well as the genu of the internal capsule,
      cerebral peduncles and corpus callosum. The linear increase in FA with cortical
      excitability as indexed by the MT remained significant after controlling for
      differences in handedness or coil-cortex distance. The posterior limb of the
      internal capsule, where fast-conducting corticospinal fibres from M1(Hand) pass
      through, showed only a weak linear relationship between FA and MT. The FA
      measurements show that a high level of corticospinal excitability is associated
      with a higher fibre coherence in large parts of cerebral white matter. The higher
      FA values in the white matter beneath premotor and motor cortices may reflect a
      structural property of cortico-cortical connections that renders M1(Hand) more
      susceptible to TMS-induced trans-synaptic excitation of the corticospinal fibres
      and may account for the inverse linear relationship between MT and FA.

PMID- 18342541
TI  - Indirect measurement of regional axon diameter in excised mouse spinal cord with
      q-space imaging: simulation and experimental studies.
AB  - Q-space imaging (QSI), a diffusion MRI technique, can provide quantitative tissue
      architecture information at cellular dimensions not amenable by conventional
      diffusion MRI. By exploiting regularities in molecular diffusion barriers, QSI
      can estimate the average barrier spacing such as the mean axon diameter in white
      matter (WM). In this work, we performed ex vivo QSI on cervical spinal cord
      sections from healthy C57BL/6 mice at 400 MHz using a custom-designed uniaxial
      50T/m gradient probe delivering a 0.6 microm displacement resolution capable of
      measuring axon diameters on the scale of 1 microm. After generating QSI-derived
      axon diameter maps, diameters were calculated using histology from seven WM
      tracts (dorsal corticospinal, gracilis, cuneatus, rubrospinal, spinothalamic,
      reticulospinal, and vestibulospinal tracts) each with different axon diameters.
      We found QSI-derived diameters from regions drawn in the seven WM tracts (1.1 to
      2.1 microm) to be highly correlated (r(2)=0.95) with those calculated from
      histology (0.8 to 1.8 microm). The QSI-derived values overestimated those
      obtained by histology by approximately 20%, which is likely due to the presence
      of extra-cellular signal. Finally, simulations on images of synthetic circular
      axons and axons from histology suggest that QSI-derived diameters are informative
      despite diameter and axon shape variation and the presence of intra-cellular and
      extra-cellular signal. QSI may be able to quantify nondestructively changes in WM
      axon architecture due to pathology or injury at the cellular level.

PMID- 18342542
TI  - Classification images reveal the information sensitivity of brain voxels in fMRI.
AB  - Reverse correlation methods have been widely used in neuroscience for many years
      and have recently been applied to study the sensitivity of human brain signals
      (EEG, MEG) to complex visual stimuli. Here we employ one such method, Bubbles
      (Gosselin, F., Schyns, P.G., 2001. Bubbles: A technique to reveal the use of
      information in recognition tasks. Vis. Res. 41, 2261-2271), in conjunction with
      fMRI in the context of a 3AFC facial expression categorization task. We highlight
      the regions of the brain showing significant sensitivity with respect to the
      critical visual information required to perform the categorization judgments.
      Moreover, we reveal the actual subset of visual information which modulates BOLD
      sensitivity within each such brain region. Finally, we show the potential which
      lies within analyzing brain function in terms of the information states of
      different brain regions. Thus, we can now analyse human brain function in terms
      of the specific visual information different brain regions process.

PMID- 18342543
TI  - Impact of inconsistent resolution on VBM studies.
AB  - This paper considers the effects of using magnetic resonance scans with different
      voxel dimensions in voxel-based morphometry studies. This is of potential
      relevance to many longitudinal studies or any ad-hoc study that relies on pre
      existing databases of subjects. In order to study this effect, a group of
      controls were contrasted with a group of semantic dementia as well as with a
      group of Alzheimer's disease patients using a mixture of different voxel
      dimensions scans on each side of the statistical test. Scans were interpolated
      using a sinc function in order to obtain a different voxel depth. The effects
      were measured by comparing the output of each analysis to the benchmark in which
      all scans had the original depth (and highest resolution), both visually and
      through the computation of the root-mean-square error difference between the
      resulting t-maps. It was shown that the impact is highly dependent on the scan
      itself, with some images showing more robustness to the interpolation process,
      and hence yielding fewer differences. A measure of robustness is proposed, which
      may be used in order to understand the impact of mixing different dimensions or
      adjusting them for each scan. Indiscriminate use of voxel dimensions on both
      groups was found to produce more errors (false positives/false negatives) than
      does an approach involving the use of balanced groups and a voxel dimension
      nuisance covariate.

PMID- 18342544
TI  - The neural basis of belief encoding and integration in moral judgment.
AB  - Moral judgment in the mature state depends on "theory of mind", or the capacity
      to attribute mental states (e.g., beliefs, desires, and intentions) to moral
      agents. The current study uses functional magnetic resonance imaging (fMRI) to
      investigate the cognitive processes for belief attribution in moral judgment.
      Participants read vignettes in a 2x2x2 design: protagonists produced either a
      negative or neutral outcome, based on the belief that they were causing the
      negative outcome or the neutral outcome; presentation of belief information
      either preceded or followed outcome information. In each case, participants
      judged the moral permissibility of the action. The results indicate that while
      the medial prefrontal cortex is recruited for processing belief valence, the
      temporo-parietal junction and precuneus are recruited for processing beliefs in
      moral judgment via two distinct component processes: (1) encoding beliefs and (2)
      integrating beliefs with other relevant features of the action (e.g., the
      outcome) for moral judgment.

PMID- 18342545
TI  - Interposition arthroplasty of the elbow with hinged external fixation for post
      traumatic arthritis.
AB  - This retrospective case series reviewed 9 men and 4 women (mean age, 41 years)
      with severe post-traumatic elbow arthrosis treated with interposition
      arthroplasty and temporary hinged external fixation. In 2 patients, treatment was
      considered to have failed because of early postoperative instability, and their
      results were classified as poor. The remaining 11 were followed up for a mean of
      4 years (range, 1-11 years). The mean arc of flexion improved from 48 degrees
      before surgery to 110 degrees after surgery. The mean postoperative Broberg
      Morrey score was 77 points, reflecting a mean improvement of 41 points (range, 13
      68 points) and corresponding with 1 excellent, 4 good, 4 fair, and 4 poor
      results. Four patients had severe instability associated with bone loss of the
      distal humerus or trochlear notch. Interposition arthroplasty can improve elbow
      motion and function but at the expense of elbow stability despite hinged external
      fixation.

PMID- 18342546
TI  - Electromyographic analysis of muscle function after latissimus dorsi tendon
      transfer.
AB  - The latissimus dorsi transfer is an established method for irreparable tears of
      the rotator cuff. The original task of the muscle is to move the arm downward and
      to rotate it internally. After the transfer, it has to perform the completely new
      function of elevating the arm. We used surface electromyography to calculate the
      mean values of the activity pattern in relation to the Constant score in 45
      patients. We assessed patients after 6 weeks and at 6, 9, and 19 months. After
      the operation, most patients showed a typical activity pattern of the latissimus
      dorsi on electromyography, which improved in the course of the study. We also
      found a strong correlation between the activity pattern on electromyography and
      the Constant score in different areas. We conclude that the functional
      improvement is due to an active muscle contraction as shown on electromyography
      and is not just an interposition or tenodesis effect.

PMID- 18342547
TI  - Rotator interval dimensions in different shoulder arthroscopy positions: a
      cadaveric study.
AB  - The rotator interval was defined as a triangular structure, where the base of the
      triangle was the coracoid base, the upper border was the anterior margin of the
      supraspinatus, and the lower border was the superior margin of the subscapularis
      muscle-tendon unit. We evaluated the rotator interval dimensions in 15 shoulders
      from 10 lightly embalmed adult cadavers in 3 shoulder arthroscopy positions: 0
      degrees of abduction and 30 degrees of flexion (beach chair [BC]), 45 degrees of
      abduction and 30 degrees of flexion (lateral decubitus 1), and 70 degrees of
      abduction and 30 degrees of flexion (lateral decubitus 2). In each shoulder
      position, measurements were made in neutral rotation (NR), 45 degrees of external
      rotation (ER), and 45 degrees of internal rotation (IR). The coracoid base
      lengthened with IR in all positions and shortened in ER in the lateral decubitus
      position but not in the BC position. Abduction significantly lengthened the
      coracoid base, which was shortest in the BC position with ER (24 +/- 4 mm) and
      longest in the lateral decubitus 2 position with IR (33 +/- 5 mm). The coracoid
      base, where sutures are placed during plication of the interval, was observed to
      lengthen and, therefore, loosen with IR and abduction. To prevent postoperative
      ER restriction, plication should be made in ER or neutral rotation when operating
      in the BC position and the degree of abduction should be decreased and the
      shoulder held in ER when operating in the lateral decubitus position.

PMID- 18342548
TI  - Open intercondylar fractures of the distal humerus: Management using a mini
      external fixator construct.
AB  - Intercondylar fractures of the distal humerus are a challenging entity to treat.
      Open reduction-internal fixation with plating is well accepted as the standard
      treatment for these fractures, because it allows early mobilization and prevents
      joint stiffness. However, this technique may be associated with inferior
      postoperative results and a higher risk of infection in open fractures. External
      fixation appears to be an interesting option in such cases, where the results of
      open reduction-internal fixation with plating may be suboptimal. We present a
      bilateral uniplanar mini-external fixator construct for the treatment of open
      intercondylar distal humeral fractures. We managed 8 cases with this external
      fixation technique, with 6 of 8 patients achieving good to excellent results as
      determined by Cassebaum's rating system.

PMID- 18342549
TI  - In vivo imaging of cartilage degeneration using microCT-arthrography.
AB  - OBJECTIVE: In vivo imaging of cartilage degeneration in small animal models is
      nowadays practically impossible. In the present study, we investigated the use of
      micro-computed tomography (microCT) in combination with a negatively charged
      ionic iodine dimer (ioxaglate) for in vivo assessment of cartilage degeneration
      in a small animal model. METHODS: Cartilage degeneration was induced in the right
      knee of rats by injection of mono-iodoacetate (MIA). We imaged the rat knees with
      ioxaglate enhanced microCT-arthrography at 4, 16 and 44 days after MIA injection.
      Subsequently, microCT-arthrographic findings were evaluated and compared with
      quantitative histology of the patellar cartilage. RESULTS: In vivo microCT
      arthrography clearly detected cartilage degeneration in the rat knee-joints, in
      which the ioxaglate diffused into the degenerated cartilage layer. Higher microCT
      attenuation values and smaller total volumes of the cartilage layer were detected
      at longer time periods after MIA injection, which is quantitatively confirmed by
      histology. CONCLUSION: In vivo microCT-arthrography is a valuable tool for
      detection of minor cartilage alterations and distinguishes different stages of
      cartilage degeneration in a small animal model. Since microCT, at the same time,
      also visualizes osteophyte formation and changes in the underlying subchondral
      bone structures, the technique will be very useful for longitudinal overall
      assessment of the development of (osteo)arthritis and to study interventions in
      small animal models.

PMID- 18342550
TI  - A 160 kDa protein with carbonic anhydrase activity is complexed with rubisco on
      the outer surface of thylakoids.
AB  - This study provides evidence that, in the soluble fraction from buffer-washed pea
      thylakoids, one form of soluble carbonic anhydrase (CA) is associated with
      rubisco in a stromal protein complex. On native-PAGE gels, it is present as a
      protein band with MW approximately 160 kDa. On SDS-PAGE gels, it is resolved as a
      single 25-kDa polypeptide. Analysis of Western blots developed with polyclonal
      antibodies to barley rubisco and to soluble pea CA shows that a 160-kDa protein
      with CA activity is associated with rubisco in a protein complex localized on the
      outer surface of thylakoid membranes.

PMID- 18342551
TI  - Differential role of the hippocampal endocannabinoid system in the memory
      consolidation and retrieval mechanisms.
AB  - CB1 cannabinoid receptors are abundantly expressed in the brain, with large
      concentrations present in the hippocampus, a brain structure essential for memory
      processing. In the present study, we have investigated the possible modulatory
      role of the endocannabinoid system in the dorsal hippocampus upon the different
      phases of memory processing of an aversive task. AM251, a selective antagonist of
      CB1 receptors, and anandamide, an endogenous agonist of cannabinoid receptors,
      were bilaterally infused into the dorsal hippocampus of male Wistar rats either
      before training, immediately after training, or before test in the step-down
      inhibitory avoidance (IA) task. Results showed that pre-training infusion of CB1
      drugs did not influence the acquisition of the task. In contrast, post-training
      infusion of the CB1 antagonist disrupted while the antagonist facilitated memory
      consolidation of IA. The post-training results demonstrate that memory
      consolidation depends on the integrity of the endocannabinoid system in the CA1
      region of the dorsal hippocampus. While we still have no direct proof of
      endocannabinoids released there after an aversive task such as IA, these results
      suggests that (a) AM251 acts blocking the binding of endogenously released
      cannabinoids and (b) exogenously supplemented anandamide may be adding its
      contribution to the action of the endogenously released pool. Considering our
      data and the higher density of CB1 receptors present in the GABAergic
      interneurons, we propose them as the putative target of the endocannabinoid
      modulation of memory, a hypothesis that needs to be proven. In addition, pre-test
      infusion of the CB1 receptor antagonist facilitated while infusion of the agonist
      did not affect memory retrieval of IA. The completely opposite action of the same
      drug upon memory at the post-training (consolidation) and pre-test (recall)
      contexts suggests that some durable change took place in the CA1 region during
      the consolidation process that modified the logical attributes of the
      pharmacological response, i.e., the drug response changed from memory disruption
      to memory facilitation. A similar phenomenon was previously described by us in
      the M4 cholinergic muscarinic subsystem in the hippocampus for the same task
      (Diehl, F., Furstenau, L. O., Sanchez, G., Camboim, C., de Oliveira Alvares, L.,
      Lanziotti, V. B., et al. (2007). Facilitatory effect of the intra-hippocampal
      pretest administration of MT3 in the inhibitory avoidance task. Behavioral Brain
      Research, 177(2), 227-231), but the biological nature of such change in the local
      neural circuitry remains to be investigated.

PMID- 18342553
TI  - Basophils play a pivotal role in immunoglobulin-G-mediated but not immunoglobulin
      E-mediated systemic anaphylaxis.
AB  - Anaphylaxis is an acute, severe, and potentially fatal systemic allergic
      reaction. Immunoglobulin E (IgE), mast cells, and histamine have long been
      associated with anaphylaxis, but an alternative pathway mediated by IgG has been
      suggested to be more important in the elicitation of anaphylaxis. Here, we showed
      that basophils, the least common blood cells, were dispensable for IgE-mediated
      anaphylaxis but played a critical role in IgG-mediated, passive and active
      systemic anaphylaxis in mice. In vivo depletion of basophils but not macrophages,
      neutrophils, or NK cells ameliorated IgG-mediated passive anaphylaxis and rescued
      mice from death in active anaphylaxis. Upon capture of IgG-allergen complexes,
      basophils released platelet-activating factor (PAF), leading to increased
      vascular permeability. These results highlight a pivotal role for basophils in
      vivo and contrast two major, distinct pathways leading to allergen-induced
      systemic anaphylaxis: one mediated by basophils, IgG, and PAF and the other
      "classical" pathway mediated by mast cells, IgE, and histamine.

PMID- 18342552
TI  - The signal transducer STAT5 inhibits plasmacytoid dendritic cell development by
      suppressing transcription factor IRF8.
AB  - The development of distinct dendritic cell (DC) subsets is regulated by
      cytokines. The ligand for the FMS-like tyrosine kinase 3 receptor (Flt3L) is
      necessary for plasmacytoid DC (pDC) and conventional DC (cDC) maturation. The
      cytokine GM-CSF inhibits Flt3L-driven pDC production while promoting cDC growth.
      We show that GM-CSF selectively utilized its signal transducer STAT5 to block
      Flt3L-dependent pDC development from the lineage-negative, Flt3+ (lin- Flt3+)
      bone-marrow subset. The signaling molecule STAT3, by contrast, was necessary for
      expansion of DC progenitors but not pDC maturation. In vivo, STAT5 suppressed pDC
      formation during repopulation of the DC compartment after bone-marrow ablation.
      GM-CSF-dependent STAT5 signaling rapidly extinguished pDC-related gene expression
      in lin- Flt3+ progenitors. Inspection of the Irf8 promoter revealed that STAT5
      was recruited during GM-CSF-mediated suppression, indicating that STAT5 directly
      inhibited transcription of this critical pDC gene. Our results therefore show
      that GM-CSF controls the production of pDCs by employing STAT5 to suppress IRF8
      and the pDC transcriptional network in lin- Flt3+ progenitors.

PMID- 18342554
TI  - The role of mycotoxins in the health and performance of dairy cows.
AB  - In comparison to monogastric species, ruminant animals are generally considered
      to be less susceptible to the adverse effects caused by contamination of feeds
      with mycotoxins. This is based on the assumption that the rumen flora degrade and
      inactivate mycotoxins, thus protecting the animal. A number of mycotoxins,
      however, resist rumen degradation, causing distinct clinical signs of
      intoxication. Moreover, due to their complex diet, dairy cows may be exposed to a
      varying number of mycotoxins, originating from different feed materials such as
      roughage and concentrates. Exposure to these complex mixtures of mycotoxins may
      result in unexpected health risks. Due to a pre-existing negative energy balance,
      cows in the transition period are considered to be particularly sensitive to the
      exposure to feeds contaminated with moulds, fungal spores and mycotoxins.

PMID- 18342555
TI  - The monitoring, prevention, and treatment of milk fever and subclinical
      hypocalcemia in dairy cows.
AB  - The periparturient cow undergoes a transition from non-lactating to lactating at
      calving. The animal is tremendously challenged to maintain calcium homeostasis.
      Those that fail can develop milk fever, a clinical disorder that is life
      threatening to the cow and predisposes the animal to a variety of other
      disorders. Guidelines for monitoring the incidence of hypocalcemia and methods
      for treating milk fever are reviewed. The physiological factors that cause milk
      fever and strategies for prevention of milk fever are discussed, focusing on the
      effects diet cation-anion difference can have on tissue sensitivity to
      parathyroid hormone. Another major risk factor for milk fever is hypomagnesemia,
      which is observed when animals are fed inadequate amounts of magnesium, or some
      factor is present in the diet that prevents adequate absorption of magnesium.
      Moderate hypomagnesemia impairs the ability of the cow to maintain calcium
      homeostasis and hypocalcemia occurs.

PMID- 18342556
TI  - Production diseases of the transition cow.
AB  - Production diseases of the dairy cow are caused by a level of production
      inconsistent with nutrient intake, provision of an inadequate diet, an unsuitable
      environment, an inappropriate breeding policy or various combinations of these
      factors. Although the transition period of 3 weeks pre-calving until 3 weeks post
      calving is associated with a peak incidence of production disease, the effects of
      these diseases on dairy cow health and productivity extend far into the following
      lactation. Recent advances in understanding of production diseases include the
      emergence of propylene glycol and rumen protected choline as the supplements of
      choice for preventing fatty liver and the absence of any preventative effect of
      increased energy density in the close-up dry period diet on this condition; the
      linear negative influence of dietary cation anion difference (DCAD) on the
      incidence of milk fever regardless of urinary pH or the target level of dietary
      DCAD achieved; the inflammatory response associated with subacute rumen acidosis
      and its effect on feed intake; an increased awareness of the potential for
      antioxidant status to improve immunity and health in the transition period; the
      development of more standardised diagnostic criteria and treatment protocols for
      uterine infection. A significant body of knowledge already exists which should
      allow for the optimal management and prevention of bovine production diseases.
      One of the important challenges facing the dairy industry is the development,
      implementation and economic assessment of practical, integrated, blueprints of
      best practice for prevention of the production diseases and other diseases of the
      dairy cow.

PMID- 18342557
TI  - Neck muscles' cross-sectional area in adolescents with and without headache - MRI
      study.
AB  - BACKGROUND: Cervical musculature may play an important role in the genesis of
      tension-type headache. However, there are no reports on a possible association
      between the morphometrical features of the neck flexion and extension muscles and
      adolescence headache. AIM: To examine differences in neck flexion and extension
      muscles cross-sectional area (CSA) in adolescents with and without headache.
      METHODS: A population-based sample of 17-year-old adolescents with migraine
      (N=19), tension-type headache (N=24) and healthy controls without headache (N=22)
      was examined. CSA of the neck muscles was measured from axial T1-weighted
      magnetic resonance images (MRI). RESULTS: Boys with tension-type headache showed
      significantly smaller CSA of right sternocleidomastoid muscle than boys with
      migraine and girls with tension-type headache showed significantly smaller CSA of
      combined right sternocleidomastoid and scalenus muscles than girls with migraine.
      In addition, boys with migraine had significantly larger CSA of both right
      sternocleidomastoid and combined right sternocleidomastoid and scalenus muscles,
      and left semispinalis capitis muscle and combined left semispinalis and splenius
      muscles than boys without headache. In boys and girls no other significant
      differences were observed in the CSA of neck flexion or extension muscles.
      CONCLUSIONS: This preliminary work demonstrates that both girls and boys with
      tension-type headache and migraine have differences in the size of neck flexion
      muscles, especially unilaterally. In boys, unilaterally increased size of neck
      flexion and extension muscles is associated with migraine. These findings, if
      confirmed in further studies, may have important diagnostic and therapeutic
      implications for rehabilitation of adolescents with headache.

PMID- 18342558
TI  - Magnetic resonance in systems with equivalent spin-1/2 nuclides. Part 2: energy
      values and spin states.
AB  - In an earlier paper (Part 1), featuring group-theoretical analysis, it was shown
      that the isotropic EPR spectra of free radical (S=1/2) species XL(n), where the n
      equivalent nuclei also have spin 1/2, have a more complicated form than
      anticipated from the usual (first-order) oversimplified analysis. The nucleus of
      X is taken to be spin-less. The latter predicts n+1 lines with intensity ratios
      given by the coefficients of the binomial expansion; for systems with n=3, the
      EPR spectrum in fact consists of 6 lines. Analogous considerations hold for NMR
      spectroscopy of XL(n) non-radicals. For n > or = 3 systems, the degeneracy of the
      energy levels cannot be completely removed by the Zeeman electronic and nuclear
      interactions. Explicit solutions for n=3 (analytic, as well as computational) of
      the spin-hamiltonian for the energies and spin states have been obtained and are
      given in the present work. Discussion of the underlying theory, invoking exchange
      degeneracy, is included herein in some detail, focusing on line positions and
      relative spectral intensities.

PMID- 18342559
TI  - Acute effects of sildenafil on exercise pulmonary hemodynamics and capacity in
      patients with COPD.
AB  - BACKGROUND: We investigated in chronic obstructive pulmonary disease (COPD)
      patients whether a single dose of sildenafil can attenuate the exercise-induced
      increase in pulmonary artery pressure, thereby allowing augmentation of stroke
      volume (SV), and improving maximal exercise capacity. METHODS: Eighteen COPD
      patients (GOLD II-IV) underwent right heart catheterization at rest and
      submaximal exercise. Mean pulmonary artery pressure (mPpa) and cardiac output
      (CO) were assessed. Resting and exercise measurements were repeated 60 min after
      oral intake of 50mg sildenafil. Also, on different days, patients performed two
      maximal exercise tests (CPET) randomly, 1h after placebo and after 50mg
      sildenafil. RESULTS: Five COPD patients had pulmonary hypertension (PH) at rest
      (mPpa >25 mmHg) and six developed PH during exercise (mPpa >30 mmHg). In all
      patients, mPpa increased from rest to submaximal exercise (23+/-10-35+/-14 mmHg).
      After sildenafil mPpa at rest was 20+/-10 mmHg, in exercise mPpa was increased
      less to 30+/-14 mmHg (p<0.01). The reduced augmentation in mPpa was not
      accompanied by an increased SV and CO. In COPD patients with PH the percentage
      increase in mPpa to submaximal exercise was 68% before, and 51% after oral intake
      of sildenafil (p=0.07). In COPD without PH, these values were 46% and 41% (ns),
      respectively. Maximal exercise capacity and CPET characteristics were unchanged
      after sildenafil. CONCLUSION: Regardless of mPpa at rest, sildenafil attenuates
      the increase in mPpa during submaximal exercise in COPD. This attenuated increase
      is neither accompanied by enhanced SV and CO, nor by improved maximal exercise
      capacity.

PMID- 18342560
TI  - Introduction to the pulmonary research group's symposium upper airway disease:
      clinical and research perspectives.

PMID- 18342561
TI  - Comparison of antimicrobial activity in the epidermal mucus extracts of fish.
AB  - The mucus layer on the surface of fish consists of several antimicrobial agents
      that provide a first line of defense against invading pathogens. To date, little
      is known about the antimicrobial properties of the mucus of Arctic char
      (Salvelinus alpinus), brook trout (S. fontinalis), koi carp (Cyprinus carpio sub
      sp. koi), striped bass (Morone saxatilis), haddock (Melanogrammus aeglefinus) and
      hagfish (Myxine glutinosa). The epidermal mucus samples from these fish were
      extracted with acidic, organic and aqueous solvents to identify potential
      antimicrobial agents including basic peptides, secondary metabolites, aqueous and
      acid soluble compounds. Initial screening of the mucus extracts against a
      susceptible strain of Salmonella enterica C610, showed a significant variation in
      antimicrobial activity among the fish species examined. The acidic mucus extracts
      of brook trout, haddock and hagfish exhibited bactericidal activity. The organic
      mucus extracts of brook trout, striped bass and koi carp showed bacteriostatic
      activity. There was no detectable activity in the aqueous mucus extracts. Further
      investigations of the activity of the acidic mucus extracts of brook trout,
      haddock and hagfish showed that these fish species had specific activity for fish
      and human pathogens, demonstrating the role of fish mucus in antimicrobial
      protection. In comparison to brook trout and haddock, the minimum bactericidal
      concentrations of hagfish acidic mucus extracts were found to be approximately
      1.5 to 3.0 times lower against fish pathogens and approximately 1.6 to 6.6 folds
      lower for human pathogens. This preliminary information suggests that the mucus
      from these fish species may be a source of novel antimicrobial agents for fish
      and human health related applications.

PMID- 18342562
TI  - Assembly and disassembly dynamics of the cyanobacterial periodosome.
AB  - In vitro incubation of three Kai proteins, KaiA, KaiB, and KaiC, with ATP induces
      a KaiC phosphorylation cycle that is a potential circadian clock pacemaker in
      cyanobacterium Synechococcus elongatus PCC 7942. The Kai proteins assemble into
      large heteromultimeric complexes (periodosome) to effect a robust oscillation of
      KaiC phosphorylation. Here, we report real-time measurements of the
      assembly/disassembly dynamics of the Kai periodosome by using small-angle X-ray
      scattering and determination of the low-resolution shapes of the KaiA:KaiC and
      KaiB:KaiC complexes. Most previously identified period-affecting mutations could
      be mapped to the association interfaces of our complex models. Our results
      suggest that the assembly/disassembly processes are crucial for phase entrainment
      in the early synchronizing stage but are passively driven by the phosphorylation
      status of KaiC in the late oscillatory stage. The Kai periodosome is assembled in
      such a way that KaiA and KaiB are recruited to a C-terminal region of KaiC in a
      phosphorylation-dependent manner.

PMID- 18342563
TI  - Correlation between compression, tensile and tearing tests on healthy and
      calcified aortic tissues.
AB  - An anastomosis performed in calcified tissues tears up faster than in healthy
      tissues. This study develops and validates an in vitro non-destructive method to
      distinguish healthy from calcified aortic tissues. An uniaxial unconfined
      compression test is able to distinguish healthy from calcified aortas (p<0.01).
      The compressive E-modulus at a strain level of 10% is 227+/-34kPa for
      artificially calcified and 147+/-15kPa for healthy porcine aortic tissues.
      Calcified aortic tissues have a lower tensile strength than healthy porcine
      aortic tissues (p<0.05). The ultimate tensile strength is 1.34+/-0.18MPa and
      1.55+/-0.31MPa for artificially calcified and healthy porcine aortic tissues
      respectively. Calcified aortic tissues have a lower resistance to tearing than
      healthy aortic tissues (p<0.05). The resistance to tearing is 1.78+/-0.33N/mm and
      2.16+/-0.64N/mm for artificially calcified and healthy porcine aortic tissues
      respectively.

PMID- 18342564
TI  - Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss
      family.
AB  - AIM: To describe a large family with autosomal dominant parkinsonism. BACKGROUND:
      Seven genes are directly implicated in autosomally inherited parkinsonism.
      However, there are several multigenerational large families known with no
      identifiable mutation. MATERIAL AND METHODS: Family members were evaluated
      clinically, by history and chart review. Genetic investigation included SCA2,
      SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The
      proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was
      available. RESULTS: Eleven patients had a diagnosis of Parkinson's disease (PD),
      nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive
      parkinsonism. Disease progression was slow but severe motor fluctuations
      occurred. One patient required subthalamic nucleus deep-brain stimulation with a
      good motor outcome. One patient had mental retardation, schizophrenia and became
      demented, and another patient was demented. Three patients and also two
      unaffected subjects had mild learning difficulties. All genetic tests yielded
      negative results. FD-PET showed marked asymmetric striatal tracer uptake
      deficiency, consistent with PD. Pathological examination demonstrated no Lewy
      bodies and immunostaining was negative for alpha-synuclein. CONCLUSION: Apart
      from a younger age of onset and a female predominance, the phenotype was
      indistinguishable from sporadic tremor-predominant PD, including FD-PET scan
      results. As known genetic causes of autosomal dominant PD were excluded, this
      family harbors a novel genetic defect.

PMID- 18342565
TI  - The persistent effects of unilateral pallidal and subthalamic deep brain
      stimulation on force control in advanced Parkinson's patients.
AB  - The persistent effects of unilateral deep brain stimulation (DBS) of the globus
      pallidus interna (GPi) or subthalamic nucleus (STN) on specific movement
      parameters produced by Parkinson's disease (PD) patients are poorly understood.
      The aim of this study was to determine the effects of unilateral GPi and STN DBS
      on the force-producing capabilities of PD patients during maximal efforts and
      functional bimanual dexterity. Clinical and biomechanical data were collected
      from 14 unilaterally implanted patients (GPi=7; STN=7), at least 13 months post
      DBS surgery, during On and Off stimulation in the absence of medication.
      Unilateral DBS of either location produced a 33% improvement in UPDRS motor
      scores. Significant gains in maximum force production were present in both limbs
      during unimanual efforts. The greatest increase in maximum force, for both limbs,
      was under bimanual conditions. Force in the contralateral limb increased more
      than 30% during bimanual efforts while ipsilateral force increased by 25%.
      Unilateral DBS improved grasping force control and consistency of digit placement
      during the performance of a bimanual dexterity task. The clinical and
      biomechanical data indicate that unilateral DBS of GPi or STN results in
      persistent improvements in the control and coordination of grasping forces during
      maximal efforts and functional dexterous actions. Unilateral DBS implantation of
      either site should be considered an option for those patients in which bilateral
      procedures are contraindicated.

PMID- 18342566
TI  - Cellular roles of ADAM12 in health and disease.
AB  - ADAM12 belongs to the large family of ADAMs (a disintegrin and metalloproteases)
      and possesses extracellular metalloprotease and cell-binding functions, as well
      as intracellular signaling capacities. Interest in ADAM12 has increased recently
      because its expression is related to tumor progression and it is a potential
      biomarker for breast cancer. It is therefore important to understand ADAM12's
      functions. Many cellular roles for ADAM12 have been suggested. It is an active
      metalloprotease, and has been implicated in insulin-like growth factor (IGF)
      receptor signaling, through cleavage of IGF-binding proteins, and in epidermal
      growth factor receptor (EGFR) pathways, via ectodomain shedding of membrane
      tethered EGFR ligands. These proteolytic events may regulate diverse cellular
      responses, such as altered cell differentiation, proliferation, migration, and
      invasion. ADAM12 may also regulate cell-cell and cell-extracellular matrix
      contacts through interactions with cell surface receptors - integrins and
      syndecans - potentially influencing the actin cytoskeleton. Moreover, ADAM12
      interacts with several cytoplasmic signaling and adaptor molecules through its
      intracellular domain, thereby directly transmitting signals to or from the cell
      interior. These ADAM12-mediated cellular effects appear to be critical events in
      both biological and pathological processes. This review presents current
      knowledge on ADAM12 functions gained from in vitro and in vivo observations,
      describes ADAM12's role in both normal physiology and pathology, particularly in
      cancer, and discusses important areas for future investigation.

PMID- 18342567
TI  - An improved system for exposure of cultured mammalian cells to gaseous compounds
      in the chromosomal aberration assay.
AB  - A gas exposure system using rotating vessels was improved for exposure of
      cultured mammalian cells to gaseous compounds in the chromosomal aberration
      assay. This system was composed of 12 square culture vessels, a device for
      preparation of air containing test gas, and positive and negative control gases
      at target concentrations and for supplying these gases to the culture vessels,
      and a roller apparatus in an incubator. Chinese hamster lung cells (CHL/IU) were
      grown on one side of the inner surface of the square culture vessel in the MEM
      medium. Immediately prior to exposure, the medium was changed to the modified
      MEM. Air in the culture vessel was replaced with air containing test gas,
      positive or negative control gas. Then, the culture vessels were rotated at 1.0
      rpm. The monolayered culture cells were exposed to test gas during about 3/4
      rotation at upper positions and alternatively immersed into the culture medium
      during about 1/4 rotation at lower positions. This system allowed the chromosomal
      aberration assay simultaneously at least at three different concentrations of a
      test gas together with positive and negative control gases with and without
      metabolic activations, and duplicate culture at each exposure concentration.
      Seven gaseous compounds, 1,3-butadiene, chlorodifluoromethane, ethyl chloride,
      methyl bromide, methyl chloride, propyne, and vinyl chloride, none of which has
      been tested to date, were tested on CHL/IU for the chromosomal aberration assay
      using this gas exposure system. All the compounds except chlorodifluoromethane
      showed positive responses of the structural chromosomal aberrations, whereas
      polyploidy was not induced by any of these gases. This improved gas exposure
      system proved to be useful for detecting chromosomal aberrations of gaseous
      compounds.

PMID- 18342568
TI  - The next innovation cycle in toxicogenomics: environmental epigenetics.
AB  - Toxicogenomics is a field that emerged from the combination of conventional
      toxicology with functional genomics. In recent years, this field contributed
      immensely in defining adverse biological effects resulting from environmental
      stressors, toxins, drugs and chemicals. Through microarray technology, large
      scale detection and quantification of mRNA transcripts and of microRNAs, related
      to alterations in mRNA stability or gene regulation became feasible. Other
      'omics' technologies, notably proteomics and metabonomics soon joined in
      providing further fine tuning in the gathering and interpretation of
      toxicological data. A field that will inevitably modify the landscape for
      toxicogenomics is 'epigenetics', a term which refers to heritable changes in gene
      expression without accompanying alterations in the DNA sequence. These epigenetic
      changes are brought about by mechanisms such as DNA methylation, histone
      modifications, and non-coding RNAs in the regulation of gene expression patterns.
      Epigenetic mechanisms are essential in normal development and differentiation,
      but these can be misdirected leading to diseases, notably cancer. Indeed, there
      is now a mounting body of evidence that environmental exposures particularly in
      early development can induce epigenetic changes, which may be transmitted in
      subsequent generations or serve as basis of diseases developed later in life. In
      either way, epigenetic mechanisms will help interpret toxicological data or
      toxicogenomic approaches to identify epigenetic effects of environmental
      exposures. Thus, a full understanding of environmental interactions with the
      genome requires keeping abreast of epigenetic mechanisms, as well as conducting
      routine analysis of epigenetic modifications as part of the mechanism of actions
      of environmental exposure. A number of approaches are currently available to
      study epigenetic modifications in a gene-specific or genome-wide manner. Here we
      describe our approaches in studying the epigenetic modification of the tumor
      suppressor gene Tslc1 (Igsf4a) in lung tumors obtained from transgenic mouse
      models.

PMID- 18342569
TI  - An evaluation of the Dental 3D Multimedia System on dentist-patient interactions:
      a report from China.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of introducing the
      Dental 3D Multimedia (D3DM) System on dentist-patient interactions. DESIGN: An
      initial version of the D3DM developed in a series of researches was applied to
      the current study. A longitudinal pre-post study was setup: volunteer patients
      answered questionnaires at three differing intervals during the course of the
      study: before the introduction of the D3DM during the first visit, after the
      introduction of the D3DM during the first visit, and after the introduction of
      the D3DM during the second visit. The questionnaires related to patient
      satisfaction and covered three main areas of interests: (1) satisfaction with
      visit components, (2) comprehension about dental issues, and (3) perceptions with
      regard to dental office computing. RESULTS: Compared with baseline, patient
      overall satisfaction increased significantly both immediately after the
      introduction of the D3DM and at the second visit. Patient's satisfaction with
      dentist's familiarity with them, and satisfaction with dental issues generally
      increased. On measures of psychological communication and available time,
      patients generally reported that no changes occurred during visits. A majority of
      participants reported that they preferred the D3DM more than traditional dentist
      patient communication patterns. There were no significant changes in patient
      perceptions of the computer use over time. CONCLUSIONS: the D3DM appeared to have
      positive effects on dentist-patient communications, improving the mutual
      understanding between them. There were no significant negative effects directly
      generated from the computer intervention. Further research is needed to update
      the current D3DM and investigate how the system might be best implemented in the
      dental office environment.

PMID- 18342570
TI  - Changes in excitability properties associated with axonal regeneration in human
      neuropathy and mouse Wallerian degeneration.
AB  - OBJECTIVE: The aim of this study was to investigate changes in excitability
      properties associated with axonal regeneration in human neuropathy and a mouse
      Wallerian degeneration model. METHODS: Threshold tracking was used to measure
      axonal excitability indices such as strength-duration time constant (SDTC),
      threshold electrotonus, supernormality in median motor axons at the wrist of 13
      patients with vasculitic neuropathy in their recovery phase, and in tibial motor
      axons at the ankle of mice with sciatic nerve crush. In the mouse model,
      excitability testing was performed 4, 8, 12, and 20weeks after the nerve crush.
      RESULTS: In patients, there were longer SDTC, greater threshold changes at 0.2ms
      in latent addition, and greater threshold changes in depolarizing and
      hyperpolarizing threshold electrotonus, compared with controls. The pattern of
      changes in excitability indices was similar to those in experimental nerve crush,
      in which the indices remained abnormal for 20weeks after the crush. These changes
      suggest an increase in nodal persistent sodium currents, whereas multiple factors
      may also contribute to changes in excitability properties, such as axonal
      hyperpolarization, increased internodal resistance, and altered potassium
      currents. CONCLUSIONS: Excitability properties in regenerating axons are
      characterized by increased nodal persistent currents with variable combination of
      changes in passive properties, membrane potential, and potassium currents.
      SIGNIFICANCE: Increased persistent sodium currents are potential reasons for
      positive symptoms in patients with axonal neuropathy. Sodium channel blockers
      could be considered a treatment option.

PMID- 18342571
TI  - Cancer survivors' views of work 3 years post diagnosis: a UK perspective.
AB  - The impact of cancer on people's working lives is an increasingly important
      concern but knowledge on this issue is very limited in the UK. Forty-one people
      of working age were purposively selected from the North Western Cancer
      Intelligence Service and interviewed by telephone to describe their experiences
      to returning to work following diagnosis and treatment. The data was subject to
      qualitative thematic analysis using NVIVO software. The results indicated the
      importance of returning to work from diagnosis and through treatment which was
      then followed by a re-assessment of work-life balance when people recovered from
      primary treatment and were back in employment. The principle motivations for
      returning to work were a quest for normality and financial pressures. One barrier
      to returning to work was the lack of medical advice from cancer specialists and
      general practitioners regarding the appropriate time to get back to work. A good
      relationship with their employer/manager was a major influence on returning to
      work and appeared to be related to duration of service rather than occupational
      status. These findings demonstrate the importance of paid work to people
      diagnosed with cancer and highlight the need to improve the support from medical
      professionals, especially oncology nurses.

PMID- 18342572
TI  - Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in
      previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase
      II non-randomised trial (FLUMIZ).
AB  - BACKGROUND: Follicular lymphoma is the most common form of lymphoma in Europe and
      the USA. In this prospective, single-arm, open-labelled, multicentre non
      randomised phase II trial (FLUMIZ [FLUdarabine, MItoxantrone, Zevalin] trial) we
      aimed to assess the efficacy and safety of fludarabine and mitoxantrone plus
      radioimmunotherapy in untreated patients with follicular non-Hodgkin lymphoma
      (NHL). METHODS: Patients with stage III or IV untreated indolent follicular NHL
      were enrolled between June 1, 2004, and April 15, 2006, at 13 Italian
      institutions, and were treated with oral fludarabine (40 mg/m2 on days 1 to 3)
      and intravenous mitoxantrone (10 mg/m2 on day 1) every 28 days for six cycles.
      Patients who had at least a partial response (PR) with normal platelet counts
      (>100x10(9)/L) and granulocyte counts (1.5x10(9)/L), and bone-marrow infiltration
      less than 25% 4-6 weeks after completion of the sixth cycle of chemotherapy were
      deemed eligible for consolidation treatment 6-10 weeks after the sixth cycle with
      one course of yttrium-90 ((90)Y)-labelled ibritumomab tiuxetan (Zevalin), which
      consisted of an initial infusion of intravenous rituximab (250 mg/m2) on day 1
      followed by a second 250 mg/m2 infusion on day 7, 8, or 9. The second infusion
      was followed by a weight-based dose of 90Y-ibritumomab tiuxetan, administered as
      a slow intravenous push over 10 min. Primary endpoints were complete response
      (CR) and haematological toxic effects and secondary endpoints were overall
      survival and progression-free survival. Responses were classified according to
      the International Workshop for Response Criteria for non-Hodgkin's lymphomas.
      Analysis was per protocol. This trial is registered as a European Standard
      Controlled Trial on the EudraCT website http://oss-sper-clin.agenziafarmaco.it,
      number 2004-002211-92. FINDINGS: 61 patients were enrolled in the trial and
      received six cycles of fludarabine and mitoxantrone, after which an overall
      response was noted in 98% (60 of 61) of patients (43 of 61 patients had CR and 17
      of 61 patients had PR). 57 patients (43 with CR and 14 with PR) were deemed
      eligible for subsequent (90)Y-ibritumomab tiuxetan. Of the 14 patients who had PR
      after the initial treatment, 12 obtained CR after (90)Y-ibritumomab tiuxetan. By
      the end of the entire treatment regimen 55 of 57 patients achieved CR. With a
      median follow-up of 30 months (range 21-48), 3-year progression-free survival was
      estimated to be 76% (95% CI 72.3-82.4) and 3-year overall survival 100%. 36 of 57
      patients had grade 3 or 4 haematological toxic effects, and blood transfusions
      were given to 21 of 57 patients. INTERPRETATION: This trial has provided evidence
      for the feasibility, tolerability, and efficacy of fludarabine and mitoxantrone
      plus (90)Y-ibritumomab tiuxetan in untreated patients with follicular NHL.

PMID- 18342573
TI  - Antigen cocktails: valid hypothesis or unsubstantiated hope?
AB  - After more than three decades of research into the development of vaccines
      against parasites, a substantial number of antigens have been identified that, as
      purified native proteins or recombinant proteins, induce some protection against
      the target parasite. Very few achieve a degree of efficacy likely to make them
      candidates for single-antigen vaccines. Therefore, multi-antigen or 'cocktail'
      vaccines are proposed based on the assumption that such cocktails will show
      enhanced efficacy. This assumption, although often poorly acknowledged, has
      become central to much vaccine research. The experimental evidence for it,
      however, is extremely scarce and contradictory. The efficacy of multicomponent
      vaccines deserves greater experimental attention than it has received.

PMID- 18342574
TI  - Sex in Plasmodium: a sign of commitment.
AB  - The gametocyte, or sexual blood-stage, of the malaria parasite represents the
      only stage of the parasite that can be transmitted to the mosquito vector
      following sexual development within the infected bloodmeal. Little is known about
      the processes leading to this cellular differentiation and specialization. The
      recent completion of the Plasmodium genome, and subsequent transcriptome and
      proteome analyses have revealed for the first time a molecular map of the genes
      that are differentially regulated at the onset of and during gametocytogenesis.
      In this review, we outline the underlying mechanisms involved in this process,
      focusing on the transition between the asexual and the sexual blood-stages of the
      parasite.

PMID- 18342575
TI  - Human monocytes represent a competitive source of interferon-alpha in peripheral
      blood.
AB  - Interferon-alpha (IFN-alpha) has a critical role in antiviral immunity and
      plasmacytoid dendritic cells (pDCs) have been demonstrated as the principal IFN
      alpha source after Toll-like receptor (TLR) 7 and 9 stimulation. Little is known
      about the contribution of pDC-independent IFN-alpha sources to total IFN-alpha
      production capacity of human peripheral blood. Using an array of pathogen
      associated molecular patterns (PAMPs), Poly(I:C)/Dotap represented the second
      strongest IFN-alpha stimulus in total PBMC. Poly(I:C)/Dotap induced three times
      more IFN-alpha, when compared to TLR7-stimulation (R848) and four times less,
      when compared to TLR9-stimulation. Dotap (mediator of cellular uptake)
      dramatically increased Poly(I:C)-induced IFN-alpha production. Sorting
      experiments and ELISpot assays revealed that monocytes and not myeloid DCs are
      the main IFN-alpha source after Poly(I:C)/Dotap stimulation. ELISpot analyses
      demonstrated the highest IFN-alpha spot numbers after Poly(I:C)/Dotap
      stimulation. Although pDCs produced highest IFN-alpha levels per cell, monocytes
      represent a competing IFN-alpha source in total PBMC due to their high frequency.

PMID- 18342576
TI  - Muscle inflammation induces a protein kinase Cepsilon-dependent chronic-latent
      muscle pain.
AB  - Skeletal muscle injuries can induce chronic pain, but the underlying mechanism is
      unknown. One possible cause has been suggested to be an increased sensitivity to
      inflammatory mediators. We demonstrate that self-limited inflammatory
      hyperalgesia induced by intramuscular carrageenan (lasting approximately 5 days)
      results in a state of chronic-latent hyperalgesia, revealed by injection of
      prostaglandin E(2) (PGE(2)) 10 days after carrageenan at the same site. In
      carrageenan-pretreated muscle, PGE(2) produced hyperalgesia that was unattenuated
      even 14 days after injection, markedly longer than the 4-hour hyperalgesia
      induced by PGE(2) in naive rats. This chronic-latent hyperalgesia was reversed as
      well as prevented by spinal intrathecal injection of oligodeoxynucleotide
      antisense to protein kinase Cepsilon, a second messenger implicated in long
      lasting plasticity in cutaneous nociceptors. PERSPECTIVE: We describe a novel
      experimental model for chronic muscle pain, produced by mild acute muscle
      inflammation, that has clinical significance since it has the potential to reveal
      cellular processes by which acute inflammation or muscle trauma underlies chronic
      muscle pain.

PMID- 18342577
TI  - Nonmedical use of prescription opioids: motive and ubiquity issues.
AB  - Two issues relating to prescription opioid nonmedical use that to our knowledge
      have not been comprehensively addressed in the peer-reviewed literature are
      discussed: Motives for nonmedical use and the extent of nonmedical use of
      prescription opioids in other countries. The United States' national annual
      survey on illicit drug use in the general population (National Survey on Drug Use
      and Health) asks respondents whether they have used prescription opioids for
      nonmedical purposes but does not assess motives for such use. By not assessing
      motives, nonmedical users who use only for pain relief and nonmedical users who
      have other motives for use are grouped together, but 2 recent epidemiological
      studies suggest that these 2 groups may differ in a propensity to have substance
      use-related problems. We suggest that the survey add a question that assesses
      motives for nonmedical use. Regarding whether countries besides the United States
      have problems associated with nonmedical use of prescription opioids, after
      searching for epidemiological surveys and other materials potentially relevant to
      this issue, we were unable to determine the extent of nonmedical use of
      prescription opioids in other countries or draw cross-national comparisons. We
      suggest that more countries include specific questions about nonmedical use of
      prescription opioids in their national epidemiological surveys. PERSPECTIVE: We
      believe that critical information surrounding the nonmedical use of prescription
      opioids is not being gathered. Such information would allow for a better
      understanding of the problem. We invite discussion and commentaries regarding the
      issues we raise to more effectively address this public health issue.

PMID- 18342579
TI  - Dipyridamole, cerebrovascular disease, and the vasculature.
AB  - Stroke is a leading cause of morbidity and mortality and the most common cause of
      neurological disability in older individuals. Prevention of recurrent stroke
      includes risk factor modification as well as the use of therapies that inhibit
      platelet activation. One such recommended therapy, dipyridamole, is given in
      combination with aspirin. Dipyridamole's inhibitory effect is thought to be due
      to inhibition of the adenosine transporter leading to an increase in cAMP, an
      inhibitor of platelet aggregation. However, recent studies suggest that
      dipyridamole possesses beneficial properties in vasculature in addition to anti
      platelet effects. This includes direct and indirect effects on the endothelium
      such as inhibition of proliferation, antioxidant, and anti-inflammatory
      properties as well as their subsequent effect on cell signaling. The purpose of
      this review is to examine whether the recently identified beneficial antioxidant
      and anti-inflammatory properties of aspirin/extended-release dipyridamole may
      partially underlie the clinical benefits observed in the secondary prevention of
      stroke.

PMID- 18342578
TI  - The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast
      lineages in Drosophila.
AB  - In both vertebrates and insects, neurons typically arise from neural stem cells
      or terminally dividing intermediate progenitors. Here, we describe another mode
      of neurogenesis where neural stem cells generate secondary precursors that
      undergo multiple rounds of self-renewing transit-amplifying divisions. We
      identify the Posterior Asense-Negative (PAN) neuroblasts, which do not express
      the transcription factors Asense or Prospero. PAN neuroblasts rely on the
      segregating determinants Numb and Brat to generate smaller, secondary neuroblasts
      that in turn give rise to ganglion mother cells (GMCs) and neurons throughout
      larval development. In brat or numb mutants, misspecified secondary neuroblasts
      are unable to produce differentiated progeny and initiate tumor-like overgrowth.
      In prospero mutants, however, tumors arise from GMCs while secondary neuroblasts
      are correctly specified. Our data describe a transit-amplifying lineage in the
      Drosophila nervous system and suggest that different vulnerabilities in
      intermediate cell types can affect the outcome of tumor suppressor loss in stem
      cell lineages.

PMID- 18342580
TI  - Association between practice patterns and body mass index percentile in infants
      and young children with cystic fibrosis.
AB  - BACKGROUND: Few guidelines focus on the preventive and maintenance care of
      infants with cystic fibrosis (CF). We explored how practice variability at
      accredited CF centers affected nutritional outcomes. METHODS: A retrospective
      cohort study using Cystic Fibrosis Foundation registry data (1993-2004) from
      three CF centers compared the initial management with respiratory, antimicrobial,
      and nutritional agents in infants. Further, we examined the association between
      dornase alpha use prior to two years of age and BMI percentile over time
      accounting for several possible factors including gender, race, CF center,
      presentation, age at diagnosis, sweat value, F508del status, first Pseudomonas
      aeruginosa infection age, second-year weight percentile, supplemental feedings
      use, and pancreatic enzymes use. RESULTS: Patient characteristics and prescribed
      therapies were similar at all sites for 165 patients who met inclusion criteria.
      However, one CF center prescribed dornase alpha significantly more frequently,
      82% vs. 10% (p<0.001), and supplemental feeds significantly less frequently, 56%
      vs. 78% (p=0.04). Dornase alpha prescription prior to age two was associated with
      a 10-percentile increase in BMI through age six compared to infants not
      prescribed dornase alpha. CONCLUSIONS: Treating infants less than two years old
      with dornase alpha may improve nutritional outcome through age six.

PMID- 18342581
TI  - 'Priming' exercise and O2 uptake kinetics during treadmill running.
AB  - We tested the hypothesis that priming exercise would speed V(O2) kinetics during
      treadmill running. Eight subjects completed a square-wave protocol, involving two
      bouts of treadmill running at 70% of the difference between the running speeds at
      lactate threshold (LT) and V(O2) max, separated by 6-min of walking at 4 km h(
      1), on two occasions. Oxygen uptake was measured breath-by-breath and
      subsequently modelled using non-linear regression techniques. Heart rate and
      blood lactate concentration were significantly elevated prior to the second
      exercise bout compared to the first. However, V(O2) kinetics was not
      significantly different between the first and second exercise bouts (mean+/-S.D.,
      phase II time constant, Bout 1: 16+/-3s vs. Bout 2: 16+/-4s; V(O2) slow component
      amplitude, Bout 1: 0.24+/-0.10 L min(-1)vs. Bout 2: 0.20+/-0.12 L min(-1); mean
      response time, Bout 1: 34+/-4s vs. Bout 2: 34+/-6s; P>0.05 for all comparisons).
      These results indicate that, contrary to previous findings with other exercise
      modalities, priming exercise does not alter V(O2) kinetics during high-intensity
      treadmill running, at least in physically active young subjects. We speculate
      that the relatively fast V(O2) kinetics and the relatively small V(O2) slow
      component in the control ('un-primed') condition negated any enhancement of V(O2)
      kinetics by priming exercise in this exercise modality.

PMID- 18342582
TI  - Determination of voriconazole in human plasma and saliva using high-performance
      liquid chromatography with fluorescence detection.
AB  - Voriconazole is a widely used triazole antifungal agent with a broad spectrum
      including Aspergillus species. A simple, sensitive and selective high-performance
      liquid chromatography method for the determination of voriconazole in human
      plasma and saliva was developed. Drug and internal standard (UK-115 794) were
      extracted from alkaline plasma and saliva with n-hexane-ethyl acetate (3:1, v/v)
      and analyzed on a Luna C 18 column with fluorimetric detection set at excitation
      and emission wavelengths of 254 and 372 nm, respectively. The calibration curve
      was linear through the range of 0.1-10 microg/ml using a 0.3 ml sample volume.
      The intra- and inter-day precisions were all below 6.1% for plasma and below 9.1%
      for saliva. Accuracies ranged from 94 to 109% for both matrices. Mean recovery
      was 86+/-4% for voriconazole. The method showed acceptable values for precision,
      recovery and sensitivity and is well suited for routine analysis work and for
      pharmacokinetic studies.

PMID- 18342583
TI  - Development and validation of a liquid chromatography-tandem mass spectrometric
      assay for pitavastatin and its lactone in human plasma and urine.
AB  - A rapid, selective and sensitive liquid chromatography-tandem mass spectrometry
      (LC-MS/MS) method with electrospray ionization (ESI) was developed and validated
      for the simultaneous determination of pitavastatin and its lactone in human
      plasma and urine. Following a liquid-liquid extraction, both the analytes and
      internal standard racemic i-prolact were separated on a BDS Hypersil C(8) column,
      using methanol-0.2% acetic acid in water (70: 30, v/v) as the mobile phase. The
      mass spectrometer was operated in multiple reaction monitoring (MRM) mode using
      the transition m/z 422.4-->m/z 290.3 for pitavastatin, m/z 404.3-->m/z 290.3 for
      pitavastatin lactone and m/z 406.3-->m/z 318.3 for the internal standard,
      respectively. Linear calibration curves of pitavastatin and its lactone were
      obtained in the concentration range of 1-200 ng/ml, with a lower limit of
      quantitation of 1 ng/ml. The intra- and inter-day precision values were less than
      4.2%, and accuracies were between -8.1 and 3.5% for both analytes. The proposed
      method was utilized to support clinical pharmacokinetic studies of pitavastatin
      in healthy subjects following oral administration.

PMID- 18342584
TI  - Development of a two-step injector for GC-MS with on-column derivatization, and
      its application to the determination of amphetamine-type stimulants (ATS) in
      biological specimens.
AB  - A two-step auto-injector has been developed for the automated on-column
      derivatization and subsequent GC-MS of amine-type drugs and metabolites. To
      effectively derivatize such analytes, this injector has been designed to inject
      the derivatization reagent several seconds after the sample has been injected.
      Eleven kinds of amphetamine-type stimulants (ATS) and their typical metabolites
      were examined, using the trifluoroacetylation reagent N-methyl
      bis(trifluoroacetamide) (MBTFA). Although the quantitative derivatization of the
      hydroxyl groups was difficult, this technique was successfully applied to the
      determination of ATS in urine, blood, and hair specimens. The detection limits of
      methamphetamine and amphetamine in hair were 0.2 and 0.1 ng/mg hair,
      respectively, in the full-scan mode, when a 10 mg hair sample is analyzed.

PMID- 18342585
TI  - Determination of the cyclic depsipeptide FK228 in human and mouse plasma by
      liquid chromatography with mass-spectrometric detection.
AB  - An analytical method was developed and validated for the quantitative
      determination of the cyclic depsipeptide FK228 (romidepsin, formerly FR901228;
      NSC 630176), a histone deacetylase inhibitor, in human and mouse plasma.
      Calibration curves were linear in the concentration range of 2-1000 ng/mL. Sample
      pretreatment involved a liquid-liquid extraction of 0.1 mL aliquots of plasma
      with ethyl acetate. FK228 and the internal standard, harmine, were separated on a
      Zorbax SB C18 column (75 mm x 2.1mm, 3.5 microm), using a mobile phase composed
      of methanol and 0.2% formic acid. The column eluent was monitored by mass
      spectrometry with electrospray ionization. Accuracy and precision of four
      concentrations of quality control samples ranged from 101.5 to 106.4% and 0.7 to
      3.5% in human plasma and 93.6 to 100.6% and 0.6 to 6.5%, in mouse plasma,
      respectively. This method represents a significant improvement over our
      previously published analytical assay for this agent, decreasing the sample
      volume requirements, increasing the accuracy and precision (through addition of a
      suitable internal standard), expanding the analytical range and validating in
      additional biological matrices. The developed method was applied to study the
      pharmacokinetics of FK228 in over 1000 clinical and preclinical samples.

PMID- 18342586
TI  - Development and validation of a liquid chromatography/tandem mass spectrometry
      assay for the simultaneous determination of nateglinide, cilostazol and its
      active metabolite 3,4-dehydro-cilostazol in Wistar rat plasma and its application
      to pharmacokinetic study.
AB  - Nateglinide (NTG), an insulin secretogogue, has been studied in rats for drug
      drug interaction with cilostazol (CLZ), an antiplatelet agent commonly used in
      diabetics. We developed a liquid chromatography tandem mass spectrometry (LC
      MS/MS) based method that is capable of simultaneous monitoring plasma levels of
      nateglinide, cilostazol, and its active metabolite 3,4-dehydro-cilostazol (DCLZ).
      All analytes including the internal standard (Repaglinide) were chromatographed
      on reverse phase C(18) column (50 mm x 4.6mm i.d., 5 microm) using acetonitrile:
      2mM ammonium acetate buffer, pH 3.4 (90:10, v/v) as mobile phase at a flow rate
      0.4 ml/min in an isocratic mode. The detection of analyte was performed on LC
      MS/MS system in the multiple reaction monitoring (MRM) mode. The quantitations
      for analytes were based on relative concentration. The method was validated over
      the concentration range of 20-2000 ng/ml and the lower limit of quantitation was
      20 ng/ml. The recoveries from spiked control samples were >79% for all analytes
      and internal standard. Intra- and inter-day accuracy and precision of validated
      method were with in the acceptable limits of <15% at all concentration. The
      quantitation method was successfully applied for simultaneous estimation of NTG,
      CLZ and DCLZ in a pharmacokinetic drug-drug interaction study in Wistar rats.

PMID- 18342587
TI  - Enantiomeric analysis of anatabine, nornicotine and anabasine in commercial
      tobacco by multi-dimensional gas chromatography and mass spectrometry.
AB  - A fully automated multi-dimensional gas chromatography (MDGC) system with a
      megabore precolumn and cyclodextrin-based analytical column was developed to
      analyze the enantiomeric compositions of anatabine, nornicotine and anabasine in
      commercial tobacco. The enantiomer abundances of anatabine and nornicotine varied
      among different tobacco. S-(-)-anatabine, as a proportion of total anatabine, was
      86.6% for flue-cured, 86.0% for burley and 77.5% for oriental tobacco. S-(-)
      nornicotine, as a proportion of total nornicotine, was 90.8% in oriental tobacco
      and higher than in burley (69.4%) and flue-cured (58.7%) tobacco. S-(-)
      anabasine, as a proportion of total anabasine, was relatively constant for flue
      cured (60.1%), burley (65.1%) and oriental (61.7%) tobacco. A simple solvent
      extraction with dichloromethane followed by derivatisation with trifluoroacetic
      anhydride gave relative standard deviations of less than 1.5% for the
      determination of the S-(-)-isomers of all three alkaloids. The study also
      indicated that, a higher proportion of S-(-)-nornicotine is related to the more
      active nicotine demethylation in the leaf.

PMID- 18342588
TI  - A cost analysis of gastro-oesophageal reflux disease and dyspepsia in Iran.
AB  - BACKGROUND AND AIM: To provide a first-time report on the health care utilization
      and costs of gastro-oesophageal reflux disease and dyspepsia in Iran. METHODS: A
      consecutive sample of 501 patients referred for upper endoscopy to an outpatient
      gastroenterology clinic in central Tehran (May 2005 to January 2006) was
      investigated using two interview-assisted questionnaires for gastro-oesophageal
      reflux disease (i.e. heartburn or regurgitation on a weekly basis for at least
      the past 3 months, and symptom onset at least 12 months prior to the study) or
      dyspepsia symptom (based on Rome II criteria). The frequency of health resource
      utilization (i.e. physician visit, hospitalization, laboratory tests,
      instrumental studies, and medications) and productivity loss (days off work) due
      to gastro-oesophageal reflux disease/dyspepsia-related symptoms in the past 12
      months were recorded. Societal perspective was used, and cost of illness per
      person per year was estimated in purchasing power parity dollars (PPP$). RESULTS:
      The cost of illness per person per year for patients with gastro-oesophageal
      reflux disease, and dyspepsia alone were around PPP$195 and PPP$215,
      respectively. There was no statistically significant difference in the cost of
      illness between the two patient groups. The direct costs of disease comprised
      88%, and 82% of the total costs in gastro-oesophageal reflux disease and
      dyspepsia patients, respectively with the costs of medications being the dominant
      component. There was also no statistically significant difference in the cost of
      disease between the gastro-oesophageal reflux disease patients with and without
      oesophagitis (based on Los Angeles criteria). CONCLUSION: As drugs cost was found
      to be a dominant cost component, cost-minimization studies to find the best
      medication therapy strategies considering the regional factors is suggested.

PMID- 18342589
TI  - Hydrolytic degradation and drug release properties of ganciclovir-loaded
      biodegradable microspheres.
AB  - The in vitro hydrolytic degradation of ganciclovir (GCV)-loaded biodegradable
      microspheres of poly(D,L-lactide) and poly(D,L-lactide-co-glycolide) polymers
      were studied. Microspheres of size 120+/-40 microm were prepared using an oil-in
      water emulsification/solvent evaporation technique. The effects of polymer
      molecular weight, lactide (LA) to glycolide (GA) ratio and GCV payload on the
      degradation and drug release profiles were investigated in vitro in phosphate
      buffered solution (pH 7.0) at 37 degrees C. GCV accelerated the hydrolysis
      process of the low (5-7 wt.%) GCV-loaded microspheres due to a basic catalytic
      effect, giving a larger degradation rate, k', compared with blank and high (18-20
      wt.%) GCV-loaded microspheres. In the high GCV-loaded microspheres, hydrolysis of
      the polymer backbone occurred with little and/or no autocatalytic effect,
      resulting in a smaller k' compared with low GCV-loaded microspheres. This was due
      to pores and microchannels created at the surface following the initial burst
      release, which increased water uptake and the dissolution and diffusion of GCV
      and degradation products from the matrix. The rate of hydrolytic degradation was
      also affected by the LA to GA ratio. For polymers of similar LA to GA ratio,
      those with a higher degree of blockiness had faster hydrolytic degradation rates
      irrespective of the initial molecular weight. The release profile had a biphasic
      pattern, which closely followed the degradation profile of the polymer. The time
      taken for the complete release of GCV was controlled by the diffusion phase and
      was dependent on the hydrolytic degradation rate of the polymers.

PMID- 18342590
TI  - Laparoscopic versus open appendicectomy in pregnancy: a systematic review.
AB  - BACKGROUND: Acute appendicitis is the most common non-obstetric indication for
      surgical intervention in pregnant women. The benefits of a laparoscopic over an
      open approach to appendicectomy are well established in the non-pregnant
      population. Data on the optimal surgical approach to acute appendicitis in
      pregnant women are conflicting. METHODS: A systematic review of reported cases of
      laparoscopic appendicectomy (LA) in pregnancy over the period 1990 to 2007.
      Twenty-eight articles documenting 637 cases of LA in pregnancy were included.
      Data on pregnancy outcome, patient characteristics, operative technique and peri
      operative complications were analysed. RESULTS: The rate of fetal loss following
      LA in pregnancy approaches 6% and is significantly higher than that following
      open appendicectomy. Fetal loss was highest in cases of complicated appendicitis.
      Incidence of preterm delivery appears lower in the LA group although this
      complication is likely to be under-reported in a significant proportion of cases.
      Trimester at the time of LA does not appear to influence complication rates. The
      negative appendicectomy rate in this series was 27%, which is higher than in the
      non-pregnant population. Complication rates following LA with negative
      appendicitis are as high as with simple appendicitis. Rates of entry-related
      complications were 2.8% in the Veress needle group and 0% in the Hasson open
      entry group. The overall rate of conversion to laparotomy was 1%. No difference
      was found in the preterm delivery rate between women who received prophylactic
      tocolysis and those who were not tocolysed. CONCLUSIONS: Laparoscopic
      appendicectomy in pregnancy is associated with a low rate of intra-operative
      complications in all trimesters. However, LA in pregnancy is associated with a
      significantly higher rate of fetal loss compared to open appendicectomy. Rates of
      preterm delivery appear similar or slightly better following a laparoscopic
      approach. Open appendicectomy would appear to be the safer option for pregnant
      women for whom surgical intervention is indicated.

PMID- 18342591
TI  - Does viewing of surgical specimen improve patient satisfaction? A cohort study.
AB  - The purpose of this study was to assess a cohort of patients who underwent
      elective gynecologic surgery to determine whether viewing of intraoperative
      photographic images by patients played a role in patient satisfaction. Three
      hundred and eighteen patients participated in this study, out of which 159
      patients were assigned to view the operative photographic pictures and 159 were
      not. According to the results obtained in this study, a greater number of women
      who viewed their operative photographic pictures, expressed satisfaction in
      comparison to those who did not. In addition, this difference was significantly
      greater in those who encountered intra- and/or postoperative complications.

PMID- 18342592
TI  - Prevention of tourniquet pain by subcutaneous injection into the posterior half
      of the axilla.

PMID- 18342593
TI  - Gomez-Lopez-Hernandez syndrome: an easily missed diagnosis.
AB  - Gomez-Lopez-Hernandez syndrome (GLHS) is a rare syndrome comprising the triad
      rhombencephalosynapsis (RS), parietal alopecia, and trigeminal anesthesia. Other
      typical findings are skull abnormalities, craniofacial dysmorphic signs, and
      short stature. Intellectual impairment is typical but cases with normal cognitive
      functions have also been reported. Only 15 cases of GLHS have been described so
      far, all sporadic. We report four further patients with GLHS: one neonate, two
      children and a middle aged man. In all cases the diagnosis was made only in
      retrospect; one child died as neonate due to esophageal atresia. All patients
      presented RS and parietal alopecia, three intermittent head stereotypies, two had
      obvious trigeminal anesthesia, and one normal cognition. Alopecia and also
      trigeminal anesthesia can be very mild and can be easily missed. However, the
      dysmorphic signs including bilateral alopecia are already present in the neonatal
      period and are highly suggestive of GLHS. RS should be looked for in this
      situation. It is important to mention that neuroimaging does not allow
      distinguishing between isolated RS and GLHS. If RS is diagnosed the clinical
      signs of GLHS should be sought. The diagnosis of GLHS can only be made by the
      combination of the typical dysmorphic signs and neuroimaging in the neonatal
      period, but not prenatally.

PMID- 18342594
TI  - A 15Mb duplication of 6q24.1-q25.3 associated with typical but milder features of
      the duplication 6q syndrome.
AB  - We report on a female patient carrying a de novo 15Mb duplication of 6q24.1-q25.3
      detected by conventional karyotyping and fine-mapped by molecular karyotyping
      with a 250K SNP array. Pure interstitial duplications of 6q are rarely reported
      in the literature and none of them exactly mapped by array technique so far. Our
      patient shows typical aspects of the "duplication 6q" syndrome such as
      hypertelorism, downslanting palpebral fissures, carp shaped mouth and joint
      contractures, but milder mental retardation and no growth retardation.

PMID- 18342595
TI  - Atypical 22q11.2 deletion in a patient with DGS/VCFS spectrum.
AB  - Deletions in region 22q11.2 usually occur between two low copy repeat regions
      (LCRs), which are preferred chromosome sites for rearrangements. Most of the
      deletions encompass the same approximately 3 or approximately 1.5 Mb region, with
      breakpoints at LCR A and D or at LCR A and B, respectively. We report on a
      patient with clinical features of the 22q deletion syndrome who presents a novel,
      atypical deletion, smaller than 1.5 Mb, with distal breakpoint in LCR B and
      proximal breakpoint within no known LCR site.

PMID- 18342596
TI  - Direct tandem duplication in chromosome 19q characterized by array CGH.
AB  - Partial trisomy of the long arm of chromosome 19 is a rare aneusomy. Only six
      cases of pure duplications have been previously reported, two of which were
      prenatally detected. Here we describe the clinical manifestations in a 15-month
      old girl with a de novo dup(19)(q12q13.2) and the application of array-based
      comparative genomic hybridization with a resolution of approximately 1 Mb to
      characterize the duplicated segment. Seven clones were found duplicated, and the
      size of the fragment was determined to be 10.8 Mb. The scarce number of patients
      reported and the difficulty of accurately defining the duplicated segment when
      conventional cytogenetic methods are applied hamper the delineation of a clinical
      phenotype for duplication of chromosome 19q. To our knowledge this is the fifth
      live born reported with a pure dup(19), and the first report in which the
      duplicated segment has been accurately characterized by means of array CGH.

PMID- 18342598
TI  - Increased mTORC1 signaling UPRegulates stress.
AB  - In this issue of Molecular Cell, Ozcan et al. (2008) show that the loss of the
      tuberous sclerosis tumor suppressor complex induces endoplasmic reticulum stress,
      leading to attenuation of insulin receptor signaling activity via the unfolded
      protein response.

PMID- 18342597
TI  - The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated
      from the cell surface by the viral Vpu protein.
AB  - The HIV-1 accessory protein Vpu counteracts a host factor that restricts virion
      release from infected cells. Here we show that the interferon-induced cellular
      protein BST-2/HM1.24/CD317 is such a factor. BST-2 is downregulated from the cell
      surface by Vpu, and BST-2 is specifically expressed in cells that support the vpu
      phenotype. Exogenous expression of BST-2 inhibits HIV-1 virion release, while
      suppression of BST-2 relieves the requirement for Vpu. Downregulation of BST-2
      requires both the transmembrane/ion channel domain and conserved serines in the
      cytoplasmic domain of Vpu. Endogenous BST-2 colocalizes with the HIV-1 structural
      protein Gag in endosomes and at the plasma membrane, suggesting that BST-2 traps
      virions within and on infected cells. The unusual structure of BST-2, which
      includes a transmembrane domain and a lumenal GPI anchor, may allow it to retain
      nascent enveloped virions on cellular membranes, providing a mechanism of viral
      restriction counteracted by a specific viral accessory protein.

PMID- 18342599
TI  - "Unraveling the tail" of how SRPK1 phosphorylates ASF/SF2.
AB  - In this issue of Molecular Cell, Ngo et al. (2008) describe the crystal structure
      of the SRPK1 protein kinase in complex with its substrate, the spliceosome factor
      ASF/SF2, providing an unprecedented view of multiple targeting mechanisms in
      action on a single substrate.

PMID- 18342600
TI  - Tbf1 or not Tbf1?
AB  - In this issue of Molecular Cell, Hogues et al. (2008) demonstrate a wholesale
      shift in the key regulatory protein involved in ribosomal protein (RP) synthesis
      during the evolution of S. cerevisiae and, en passant, raise interesting
      questions about the relationship between RP genes and telomeres.

PMID- 18342601
TI  - Tat-SIRT1 tango.
AB  - In a recent issue of Cell Host & Microbe, Kwon et al. (2008) report that the
      human immunodeficiency virus (HIV) transactivator Tat inhibits the SIRT1
      deacetylase, resulting in increased acetylation of the NF-kappaB p65 subunit and
      subsequently in T cell hyperactivation.

PMID- 18342602
TI  - Loss of the tuberous sclerosis complex tumor suppressors triggers the unfolded
      protein response to regulate insulin signaling and apoptosis.
AB  - Mammalian target of rapamycin, mTOR, is a major sensor of nutrient and energy
      availability in the cell and regulates a variety of cellular processes, including
      growth, proliferation, and metabolism. Loss of the tuberous sclerosis complex
      genes (TSC1 or TSC2) leads to constitutive activation of mTOR and downstream
      signaling elements, resulting in the development of tumors, neurological
      disorders, and at the cellular level, severe insulin/IGF-1 resistance. Here, we
      show that loss of TSC1 or TSC2 in cell lines and mouse or human tumors causes
      endoplasmic reticulum (ER) stress and activates the unfolded protein response
      (UPR). The resulting ER stress plays a significant role in the mTOR-mediated
      negative-feedback inhibition of insulin action and increases the vulnerability to
      apoptosis. These results demonstrate ER stress as a critical component of the
      pathologies associated with dysregulated mTOR activity and offer the possibility
      to exploit this mechanism for new therapeutic opportunities.

PMID- 18342603
TI  - Transcription factor substitution during the evolution of fungal ribosome
      regulation.
AB  - Coordinated ribosomal protein (RP) gene expression is crucial for cellular
      viability, but the transcriptional network controlling this regulon has only been
      well characterized in the yeast Saccharomyces cerevisiae. We have used whole
      genome transcriptional and location profiling to establish that, in Candida
      albicans, the RP regulon is controlled by the Myb domain protein Tbf1 working in
      conjunction with Cbf1. These two factors bind both the promoters of RP genes and
      the rDNA locus; Tbf1 activates transcription at these loci and is essential.
      Orthologs of Tbf1 bind TTAGGG telomeric repeats in most eukaryotes, and TTAGGG
      cis-elements are present upstream of RP genes in plants and fungi, suggesting
      that Tbf1 was involved in both functions in ancestral eukaryotes. In all
      Hemiascomycetes, Rap1 substituted Tbf1 at telomeres and, in the S. cerevisiae
      lineage, this substitution also occurred independently at RP genes, illustrating
      the extreme adaptability and flexibility of transcriptional regulatory networks.

PMID- 18342604
TI  - A sliding docking interaction is essential for sequential and processive
      phosphorylation of an SR protein by SRPK1.
AB  - The 2.9 A crystal structure of the core SRPK1:ASF/SF2 complex reveals that the N
      terminal half of the basic RS domain of ASF/SF2, which is destined to be
      phosphorylated, is bound to an acidic docking groove of SRPK1 distal to the
      active site. Phosphorylation of ASF/SF2 at a single site in the C-terminal end of
      the RS domain generates a primed phosphoserine that binds to a basic site in the
      kinase. Biochemical experiments support a directional sliding of the RS peptide
      through the docking groove to the active site during phosphorylation, which ends
      with the unfolding of a beta strand of the RRM domain and binding of the unfolded
      region to the docking groove. We further suggest that the priming of the first
      serine facilitates directional substrate translocation and efficient
      phosphorylation.

PMID- 18342605
TI  - The Glc7 phosphatase subunit of the cleavage and polyadenylation factor is
      essential for transcription termination on snoRNA genes.
AB  - Glc7, the yeast protein phosphatase 1, is a component of the cleavage and
      polyadenylation factor (CPF). Here we show that downregulation of Glc7, or its
      dissociation from CPF in the absence of CPF subunits Ref2 or Swd2, results in
      similar snoRNA termination defects. Overexpressing a C-terminal fragment of Sen1,
      a superfamily I helicase required for snoRNA termination, suppresses the growth
      and termination defects associated with loss of Swd2 or Ref2, but not Glc7.
      Suppression by Sen1 requires nuclear localization and direct interaction with
      Glc7, which can dephosphorylate Sen1 in vitro. The suppressing fragment, and in a
      similar manner full-length Sen1, copurifies with the snoRNA termination factors
      Nrd1 and Nab3, suggesting loss of Glc7 from CPF can be compensated by recruiting
      Glc7 to Nrd1-Nab3 through Sen1. Swd2 is also a subunit of the Set1c histone H3K4
      methyltransferase complex and is required for its stability and optimal
      methyltransferase activity.

PMID- 18342606
TI  - Molecular dissection of mammalian RNA polymerase II transcriptional termination.
AB  - Transcriptional termination of mammalian RNA polymerase II (Pol II) is an
      essential but little-understood step in protein-coding gene expression.
      Mechanistically, termination by all DNA-dependent RNA polymerases can be reduced
      to two steps, namely release of the RNA transcript and release of the DNA
      template. Using a simple nuclear fractionation procedure, we have monitored
      transcript and template release in the context of both natural and artificial Pol
      II terminator sequences. We describe the timing and relationship between these
      events and in so doing establish the roles of the poly(A) signal,
      cotranscriptional RNA cleavage events, and 5'-3' exonucleolytic RNA degradation
      in the mammalian Pol II termination process.

PMID- 18342607
TI  - Interaction of the glucocorticoid receptor with the chromatin landscape.
AB  - The generality and spectrum of chromatin-remodeling requirements for nuclear
      receptor function are unknown. We have characterized glucocorticoid receptor (GR)
      binding events and chromatin structural transitions across GR-induced or 
      repressed genes. This analysis reveals that GR binding invariably occurs at
      nuclease-accessible sites (DHS). A remarkable diversity of mechanisms, however,
      render these sites available for GR binding. Accessibility of the GR binding
      sites is either constitutive or hormone inducible. Within each category, some DHS
      sites require the Brg1-containing Swi/Snf complex, but others are Brg1
      independent, implicating a different remodeling complex. The H2A.Z histone
      variant is highly enriched at both inducible and constitutive DHS sites and is
      subject to exchange during hormone activation. The DHS profile is highly cell
      specific, implicating cell-selective organization of the chromatin landscape as a
      critical determinant of tissue-selective receptor function. Furthermore, the
      widespread requirement for chromatin remodeling supports the recent hypothesis
      that the rapid exchange of receptor proteins occurs during nucleosome
      reorganization.

PMID- 18342608
TI  - Activation of ubiquitin-dependent DNA damage bypass is mediated by replication
      protein a.
AB  - Replicative DNA damage bypass, mediated by the ubiquitylation of the sliding
      clamp protein PCNA, facilitates the survival of a cell in the presence of
      genotoxic agents, but it can also promote genomic instability by damage-induced
      mutagenesis. We show here that PCNA ubiquitylation in budding yeast is activated
      independently of the replication-dependent S phase checkpoint but by similar
      conditions involving the accumulation of single-stranded DNA at stalled
      replication intermediates. The ssDNA-binding replication protein A (RPA), an
      essential complex involved in most DNA transactions, is required for damage
      induced PCNA ubiquitylation. We found that RPA directly interacts with the
      ubiquitin ligase responsible for the modification of PCNA, Rad18, both in yeast
      and in mammalian cells. Association of the ligase with chromatin is detected
      where RPA is most abundant, and purified RPA can recruit Rad18 to ssDNA in vitro.
      Our results therefore implicate the RPA complex in the activation of DNA damage
      tolerance.

PMID- 18342609
TI  - Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E.
AB  - During mitosis, chromosome alignment depends on the regulated dynamics of
      microtubules and on motor protein activities. At the kinetochore, the interplay
      between microtubule-binding proteins, motors, and kinases is poorly understood.
      Cenp-E is a kinetochore-associated kinesin involved in chromosome congression,
      but the mechanism by which this is achieved is unclear. Here, we present a study
      of the regulation of Cenp-E motility by using purified full-length (FL) Xenopus
      Cenp-E protein, which demonstrates that FL Cenp-E is a genuine plus-end-directed
      motor. Furthermore, we find that the Cenp-E tail completely blocks the motility
      of Cenp-E in vitro. This is achieved through direct interaction between its motor
      and tail domains. Finally, we show that Cenp-E autoinhibition is reversed by MPS1
      or CDK1-cyclin B-mediated phosphorylation of the Cenp-E tail. This suggests a
      model of dynamic control of Cenp-E motility, and hence chromosome congression,
      dependent upon phosphorylation at the kinetochore.

PMID- 18342610
TI  - SbcCD causes a double-strand break at a DNA palindrome in the Escherichia coli
      chromosome.
AB  - Long DNA palindromes are sites of genome instability (deletions, amplification,
      and translocations) in both prokaryotic and eukaryotic cells. In Escherichia
      coli, genetic evidence has suggested that they are sites of DNA cleavage by the
      SbcCD complex that can be repaired by homologous recombination. Here we obtain in
      vivo physical evidence of an SbcCD-induced DNA double-strand break (DSB) at a
      palindromic sequence in the E. coli chromosome and show that both ends of the
      break stimulate recombination. Cleavage is dependent on DNA replication, but the
      observation of two ends at the break argues that cleavage does not occur at the
      replication fork. Genetic analysis shows repair of the break requires the RecBCD
      recombination pathway and PriA, suggesting a mechanism of bacterial DNA DSB
      repair involving the establishment of replication forks.

PMID- 18342611
TI  - Quantitative analysis of a novel glucosylated phospholipid by liquid
      chromatography-mass spectrometry.
AB  - Building upon the demonstrated presence of a new glyceroglycolipid,
      phosphatidylglucoside (PtdGlc), in rat embryonic brain tissues, we have developed
      a method to identify minute amounts of PtdGlc in cultured cells by using nano
      flow high-performance liquid chromatography and negative-ion-mode electrospray
      linear-ion trap time-of-flight mass spectrometry (LC-MS). A normal-phase silica
      gel-based column enabled us to separate PtdGlc from other lipid classes. PtdGlc
      was identified from its tandem mass spectrometry spectrum and from its retention
      time in the column. Using an internal standard collection and LC-MS, we obtained
      the linearity of PtdGlc at a range of 6.3-800 fmol per injection. We applied this
      method to analyze quantitative changes in PtdGlc in C6 glioma cells after
      cellular differentiation into GFAP-positive glial cells. PtdGlc in C6 glioma
      cells consisted exclusively of C18:0/C20:0 fatty acyl chains. Differentiation
      induced by the addition of anti-PtdGlc antibody plus cAMP in culture medium
      significantly increased the glycolipid content.

PMID- 18342612
TI  - Impurity profiling quality control testing of synthetic peptides using liquid
      chromatography-photodiode array-fluorescence and liquid chromatography
      electrospray ionization-mass spectrometry: the obestatin case.
AB  - Following several conflicting publications, the inability to reproduce the
      original findings on in vitro obestatin binding and activation of GPR39 receptors
      was recently reported by its discoverers, and several hypotheses to rationalize
      these findings were proposed. Based on one of these postulations (i.e., presence
      of impurities), peptide identity and impurity profiles were thoroughly evaluated
      on obestatin peptides obtained from five different manufacturers, as used by the
      different research groups. We found that one of the products examined was in
      reality a totally different peptide and that the quality of two-thirds of the
      other peptides was insufficient for in vitro and in vivo experiments (i.e.,
      peptide purity less than 95% and/or individual impurities exceeding 1%). These
      observations question the divergent conclusions reported in the literature about
      the activity of obestatin. Therefore, we strongly recommend appropriate quality
      control testing before using any peptides for biomedical research purposes.

PMID- 18342613
TI  - Characterization of virus-like particle assembly for DNA delivery using
      asymmetrical flow field-flow fractionation and light scattering.
AB  - This study illustrates the application of asymmetrical flow field-flow
      fractionation (AF4) and light scattering analysis during the development of a
      gene delivery vehicle based on virus-like particles (VLPs) derived from the human
      polyoma JC virus. The analytical system was created by connecting an AF4
      apparatus to the following detectors: diode array, fluorescence, multiangle light
      scattering, dynamic light scattering, and refractometer. From a single analysis,
      the molar mass, root mean square and hydrodynamic radii, composition, and purity
      of the sample could be determined. The VLPs were purified from baculovirus
      infected Sf158 insect cells overexpressing the recombinant VP1 protein using weak
      anion exchange chromatography. The VLPs were dissociated to VP1 pentamers, and
      the contaminating DNA and proteins were removed using strong anion exchange
      chromatography. The gene delivery vehicle was created by reassembling the VP1
      pentamers in the presence of the desired DNA. The newly formed VLPs encapsulated
      the DNA and were shown to be capable of delivering the gene of interest to target
      cells where it was translated into protein. This paper describes the scalable
      process that was derived to produce the VLPs and demonstrates how the AF4-based
      analytical characterization was indispensable during the development process.

PMID- 18342614
TI  - Real-time assay for monitoring membrane association of lipid-binding domains.
AB  - The C2 domain is a common protein module which mediates calcium-dependent
      phospholipid binding. Several assays have previously been developed to measure
      membrane association. However, these assays either have technical drawbacks or
      are laborious to carry out. We now present a simple solution-based turbidity
      method for rapidly assaying membrane association of single lipid-binding domains
      in real time. We used the first C2 domain of synaptotagmin 1 (C2A) as a model
      lipid-binding moiety. Our use of the common dimeric glutathione-S-transferase
      (GST) fusion tag allowed two C2A domains to be brought into close proximity.
      Consequently, calcium-triggered phospholipid binding by this artificially
      dimerized C2A resulted in liposomal aggregation, easily assayed by following
      absorbance of the solution at 350 nm. The assay is simple and sensitive and can
      be scaled up conveniently for use in a multiwell plate format, allowing high
      throughput screening. In our screens, we identified nickel as a novel activator
      of synaptotagmin 1 C2A domain membrane association. Finally, we show that the
      turbidity method can be applied to the study of other GST-tagged lipid-binding
      proteins such as epsin, protein kinase C-beta, and synaptobrevin.

PMID- 18342615
TI  - Substrate specificity of human glutamine transaminase K as an aminotransferase
      and as a cysteine S-conjugate beta-lyase.
AB  - Rat kidney glutamine transaminase K (GTK) exhibits broad specificity both as an
      aminotransferase and as a cysteine S-conjugate beta-lyase. The beta-lyase
      reaction products are pyruvate, ammonium and a sulfhydryl-containing fragment. We
      show here that recombinant human GTK (rhGTK) also exhibits broad specificity both
      as an aminotransferase and as a cysteine S-conjugate beta-lyase. S-(1,1,2,2
      Tetrafluoroethyl)-l-cysteine is an excellent aminotransferase and beta-lyase
      substrate of rhGTK. Moderate aminotransferase and beta-lyase activities occur
      with the chemopreventive agent Se-methyl-l-selenocysteine. l-3-(2
      Naphthyl)alanine, l-3-(1-naphthyl)alanine, 5-S-l-cysteinyldopamine and 5-S-l
      cysteinyl-l-DOPA are measurable aminotransferase substrates, indicating that the
      active site can accommodate large aromatic amino acids. The alpha-keto acids
      generated by transamination/l-amino acid oxidase activity of the two catechol
      cysteine S-conjugates are unstable. A slow rhGTK-catalyzed beta-elimination
      reaction, as measured by pyruvate formation, was demonstrated with 5-S-l
      cysteinyldopamine, but not with 5-S-l-cysteinyl-l-DOPA. The importance of
      transamination, oxidation and beta-elimination reactions involving 5-S-l
      cysteinyldopamine, 5-S-l-cysteinyl-l-DOPA and Se-methyl-l-selenocysteine in human
      tissues and their biological relevance are discussed.

PMID- 18342616
TI  - Function and structure of lipid storage droplet protein 1 studied in lipoprotein
      complexes.
AB  - Triglycerides (TG) stored in lipid droplets (LDs) are the main energy reserve in
      all animals. The mechanism by which animals mobilize TG is complex and not fully
      understood. Several proteins surrounding the LDs have been implicated in TG
      homeostasis such as mammalian perilipin A and insect lipid storage proteins
      (Lsd). Most of the knowledge on LD-associated proteins comes from studies using
      cells or LDs leaving biochemical properties of these proteins uncharacterized.
      Here we describe the purification of recombinant Lsd1 and its reconstitution with
      lipids to form lipoprotein complexes suitable for functional and structural
      studies. Lsd1 in the lipid bound state is a predominately alpha-helical protein.
      Using lipoprotein complexes containing triolein it is shown that PKA mediated
      phosphorylation of Lsd1 promoted a 1.7-fold activation of the main fat body
      lipase demonstrating the direct link between Lsd1 phosphorylation and activation
      of lipolysis. Serine 20 was identified as the Lsd1-phosphorylation site
      triggering this effect.

PMID- 18342617
TI  - Photophysical properties of popular fluorescent adenosine nucleotide analogs used
      in enzyme mechanism probing.
AB  - Fluorescent nucleotide analogs are widely used in mechanistic studies of
      nucleotide binding and utilizing proteins. We describe here an overview of the
      photophysical parameters of the most popular nucleotide analogs that have a
      fluorescent N-methylanthraniloyl-group attached at various positions of the
      nucleotide. Steady state absorption and fluorescence spectra of free chromophores
      depend on the type of modification (ribose, base or phosphate moiety) and the
      addition of proteins suggests that the labeled nucleotides also vary in
      sensitivity depending upon their local protein environment. Fluorescence lifetime
      measurements imply two to three lifetimes for each nucleotide with complex
      changes in dependence on solvent but more importantly also on the protein. The
      measured quantum yields quantify the increase in fluorescence for (C8)-MABA-ADP,
      MANT-ATP and (Pgamma)-MABA-ATP as 153%, 93% and 14% when bound to DnaK, ClpB and
      Trap1, respectively, compared to free in buffer solution.

PMID- 18342618
TI  - Role of cations in stability of acidic protein Desulfovibrio desulfuricans
      apoflavodoxin.
AB  - Apoflavodoxin from the sulfate reducing bacteria Desulfovibrio desulfuricans is a
      small, acidic protein with a net charge of -19 at neutral pH. Here, we show that
      monovalent cations in biologically relevant amounts have dramatic effects on
      apoflavodoxin stability. The effect is largest for Gdm(+) and decreases as a
      function of increased cation charge density (Gdm(+)>NH(4)(+)K(+) approximately
      Cs(+) approximately Na(+)>Li(+)). A linear correlation of stabilizing effects
      with cation hydration properties suggests an important role of dehydration in
      efficient cation interaction with the protein. The effects on stability are due
      to preferential binding of one cation to native apoflavodoxin and results in an
      increase in thermal midpoint of 20 degrees C and the free energy of unfolding (at
      20 degrees C) increases fivefold. Tuning of biophysical properties (such as
      folding and ligand/cofactor binding) of acidic proteins by cation binding may be
      important in vivo.

PMID- 18342619
TI  - pH and monovalent cations regulate cytosolic free Ca(2+) in E. coli.
AB  - The results here show for the first time that pH and monovalent cations can
      regulate cytosolic free Ca(2+) in E. coli through Ca(2+) influx and efflux,
      monitored using aequorin. At pH 7.5 the resting cytosolic free Ca(2+) was 0.2-0.5
      microM. In the presence of external Ca(2+) (1 mM) at alkaline pH this rose to 4
      microM, being reduced to 0.9 microM at acid pH. Removal of external Ca(2+) caused
      an immediate decrease in cytosolic free Ca(2+) at 50-100 nM s(-1). Efflux rates
      were the same at pH 5.5, 7.5 and 9.5. Thus, ChaA, a putative
      Ca(2+)/H(+)exchanger, appeared not to be a major Ca(2+)-efflux pathway. In the
      absence of added Na(+), but with 1 mM external Ca(2+), cytosolic free Ca(2+) rose
      to approximately 10 microM. The addition of Na(+)(half maximum 60 mM) largely
      blocked this increase and immediately stimulated Ca(2+) efflux. However, this
      effect was not specific, since K(+) also stimulated efflux. In contrast, an
      increase in osmotic pressure by addition of sucrose did not significantly
      stimulate Ca(2+) efflux. The results were consistent with H(+) and monovalent
      cations competing with Ca(2+) for a non-selective ion influx channel. Ca(2+)
      entry and efflux in chaA and yrbG knockouts were not significantly different from
      wild type, confirming that neither ChaA nor YrbG appear to play a major role in
      regulating cytosolic Ca(2+) in Escherichia coli. The number of Ca(2+) ions
      calculated to move per cell per second ranged from <1 to 100, depending on
      conditions. Yet a single eukaryote Ca(2+) channel, conductance 100 pS, should
      conduct >6 million ions per second. This raises fundamental questions about the
      nature and regulation of Ca(2+) transport in bacteria, and other small living
      systems such as mitochondria, requiring a new mathematical approach to describe
      such ion movements. The results have important significance in the adaptation of
      E. coli to different ionic environments such as the gut, fresh water and in sea
      water near sewage effluents.

PMID- 18342620
TI  - The self-organization of lipids and proteins of myelin at the membrane interface.
      Molecular factors underlying the microheterogeneity of domain segregation.
AB  - The advances over the last 10 years on the understanding of myelin heterogeneity
      are reviewed. The main focus is on the applicability of Langmuir monolayers,
      Langmuir-Blodgett films and some associated techniques to unravelling the
      behaviour of interfaces formed with all the components of a natural membrane.
      Lipid-protein lateral segregation appears as a major driving force to determine
      surface patterns that can change under compression from circular domains to two
      dimensional fractal structures. The major proteins of the myelin membrane induce
      lateral segregation in an otherwise homogeneous surface formed by the mixture of
      total myelin lipids. The lipid and protein components appear to distribute in the
      surface domains according to their charge, compressibility and relative molecular
      weight: myelin proteins, ganglioside GM1 and fluorescent lipid probes partition
      into liquid-expanded phase domains; other components such as phosphatidylserine
      and galactocerebroside partition into another liquid phase enriched in
      cholesterol. Simplified protein-lipid mixtures allow assessment of the
      participation of the major proteins in the two dimensional pattern development.
      One of the major myelin proteins, the Folch-Lees proteolipid, self-segregates
      into, and determines formation of, fractal-like patterns. The presence of the
      second major protein, myelin basic protein, leads to round liquid-expanded
      domains in the absence of Folch-Lees proteolipid and softens the boundaries of
      the fractal structures in its presence. The location of myelin basic protein in
      the interface is surface pressure sensitive, being slightly squeezed out at high
      surface pressure, allowing the fractal domains enriched in Folch-Lees proteolipid
      to evolve.

PMID- 18342621
TI  - Inhibition of histone deacetylase1 induces autophagy.
AB  - Autophagy is a process where cytoplasmic materials are degraded by lysosomal
      machinery. Histone deacetylase (HDAC) inhibitors induce autophagy, and HDAC6, one
      of class II HDAC isotypes, is directly involved in autophagic degradation in the
      cell. However, it is unclear if class I HDAC isotype such as HDCA1 is involved in
      this process. To investigate if class I HDAC isotype is involved in autophagy, a
      specific class I HDAC inhibitor and an siRNA of HDAC1 were used to treat HeLa
      cells. Autophagic markers were then investigated. Both inhibition and genetic
      knock-down of HDAC1 in the cells significantly induced autophagic vacuole
      formation and lysosome function. Moreover, disruption of HDAC1 leads to the
      conversion of LC3-I to LC3-II. Together, these results demonstrate that HDAC1
      could play a role in autophagy and specific inhibition of HDAC1 can induce
      autophagy.

PMID- 18342622
TI  - Increased dopaminergic signaling impairs aversive olfactory memory retention in
      Drosophila.
AB  - Dopamine is necessary for the aversive olfactory associative memory formation in
      Drosophila, but its effect on other stages of memory is not known. Herein, we
      studied the effect of enhanced dopaminergic signaling on aversive olfactory
      memory retention in flies. We used l-3,4-dihydroxyphenylalanine (l-DOPA) to
      elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning
      performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant
      flies or flies treated with the DAT inhibitor desipramine exhibited poor memory
      retention. Flies subjected to heat stress after training exhibited a decrease in
      memory. Memory was restored by blocking dopaminergic neuronal output during heat
      stress, suggesting that dopamine is involved in heat stress-induced memory
      impairment in flies. Taken together, our findings suggest that increased
      dopaminergic signaling impairs aversive olfactory memory retention in flies.

PMID- 18342623
TI  - Heparin blocks the adhesion of E. coli O157:H7 to human colonic epithelial cells.
AB  - Adhesion of Shiga toxin-producing Enterohemorrhagic Escherichia coli (EHEC)
      O157:H7 to human colonic epithelium is a critical step for infection by this type
      of bacteria. Here, we demonstrate that adherence of EHEC O157:H7 to cultured
      human colonic T84 epithelial monolayers can be blocked by heparin and heparan
      sulfate in a dose-dependent fashion. In doing this, heparin and heparan sulfate
      also prevent dysfunction of the T84 barrier and disorganization of epithelial
      tight junction protein ZO-1 caused by EHEC O157:H7. This inhibition by heparin
      and heparan sulfate seems to result from a block in the binding interactions of
      bacteria intimin with epithelial beta(1) integrins. This study provides evidence,
      for the first time, that heparin and heparan sulfate can serve as novel effective
      blockers in preventing EHEC O157:H7 infection.

PMID- 18342624
TI  - Prediction of translation initiation sites in human mRNA sequences with AUG start
      codon in weak Kozak context: A neural network approach.
AB  - Translation of eukaryotic mRNAs is often regulated by nucleotides around the
      start codon. A purine at position -3 and a guanine at position +4 contribute
      significantly to enhance the translation efficiency. Algorithms to predict the
      translation initiation site often fail to predict the start site if the sequence
      context is not present. We have developed a neural network method to predict the
      initiation site of mRNA sequences that lack the preferred nucleotides at the
      positions -3 and +4 surrounding the translation initiation site. Neural networks
      of various architectures comprising different number of hidden layers were
      designed and tested for various sizes of windows of nucleotides surrounding
      translation initiation sites. We found that the neural network with two hidden
      layers showed a sensitivity of 83% and specificity of 73% indicating a vastly
      improved performance in successfully predicting the translation initiation site
      of mRNA sequences with weak Kozak context. WeakAUG server is freely available at
      http://bioinfo.iitk.ac.in/AUGPred/.

PMID- 18342625
TI  - Altered Stra13 and Dec2 circadian gene expression in hypoxic cells.
AB  - The circadian system regulates rhythmically most of the mammalian physiology in
      synchrony with the environmental light/dark cycle. Alteration of circadian clock
      gene expression has been associated with tumour progression but the molecular
      links between the two mechanisms remain poorly defined. Here we show that Stra13
      and Dec2, two circadian transcriptional regulators which play a crucial role in
      cell proliferation and apoptosis are overexpressed and no longer rhythmic in
      serum shocked fibroblasts treated with CoCl(2,) a substitute of hypoxia. This
      effect is associated with a loss of circadian expression of the clock genes Rev
      erbalpha and Bmal1, and the clock-controlled gene Dbp. Consistently,
      cotransfection assays demonstrate that STRA13 and DEC2 both antagonize
      CLOCK:BMAL1 dependent transactivation of the Rev-erbalpha and Dbp promoters.
      Using a transplantable osteosarcoma tumour model, we show that hypoxia is
      associated with altered circadian expression of Stra13, Dec2, Rev-erbalpha, Bmal1
      and Dbp in vivo. These observations collectively support the notion that
      overexpression of Stra13 and Dec2 links hypoxia signalling to altered circadian
      clock gene expression.

PMID- 18342626
TI  - Effect of chronic alcohol consumption on Hepatic SIRT1 and PGC-1alpha in rats.
AB  - The nuclear genes, NAD-dependent deacetylase Sirtuis 1 (SIRT1) and the peroxisome
      proliferator-activated receptor-gamma coactivator1alpha (PGC-1alpha) are
      regulators of energy metabolism. Here, we studied the role of alcohol consumption
      in expression of these sensing molecules. Alcohol significantly reduced hepatic
      SIRT1 mRNA by 50% and PGC-1alpha mRNA by 46% and it significantly inhibited the
      protein expression of SIRT1 and PGC-1alpha, while the transcription factor PPAR
      gamma remained unchanged. However, when the lipid composition of the alcohol diet
      was changed by replacing long-chain triglycerides (LCT) with medium chain
      triglycerides (MCT), SIRT1 and PGC-1alpha mRNA were restored to near control
      levels. This study demonstrates that alcohol reduces key energy sensing proteins
      and that replacement of LCT by MCT affects the transcription of these genes.
      Since there is a pathophysiological link between SIRT1 and PGC-1alpha and
      mitochondrial energy, the implication of the study is that mitochondrial
      dysfunction due to alcohol abuse can be treated by dietary modifications.

PMID- 18342627
TI  - Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes
      is down regulated by insulin.
AB  - Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong
      association with type 2 diabetes with two defined risk haplotypes, HapA and
      HapB(T2D). TCF7L2 may play a role in both glucose homeostasis and adipogenesis.
      Our aim was to characterize the TCF7L2 mRNA expression and regulation in human
      adipose tissue. We quantified TCF7L2 mRNA levels in cultured human adipocytes and
      in biopsies from visceral (VAT) and subcutaneous (SAT) adipose tissue from 38
      obese non-diabetic subjects, using real-time PCR. The influence of haplotype and
      clinical traits on TCF7L2 mRNA levels were investigated. In vitro, insulin
      decreased TCF7L2 mRNA expression. This effect was attenuated in cells incubated
      with the free fatty acids palmitate or oleate. In vivo, we found significantly
      higher expression in SAT from more insulin resistant subjects. No correlations
      between TCF7L2 mRNA expression and obesity measures were observed. TCF7L2
      expression was higher in VAT than in SAT and when stratifying for haplotype, this
      difference was seen in HapA carriers but not in non-HapA carriers. In conclusion,
      TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in
      insulin resistant subjects and in HapA carriers.

PMID- 18342628
TI  - PKCdelta mediates thrombin-augmented fibroblast-mediated collagen gel
      contraction.
AB  - Fibroblast-mediated collagen gel contraction has been used as an in vitro model
      of tissue remodeling. Thrombin is one of the mediators present in the milieu of
      airway inflammation and may be involved in airway tissue remodeling. We have
      previously reported that thrombin stimulates fibroblast-mediated collagen gel
      contraction partially through the PAR1/PKCepsilon signaling pathway [Q. Fang, X.
      Liu, S. Abe, T. Kobayashi, X.Q. Wang, T. Kohyama, M. Hashimoto, T. Wyatt, S.I.
      Rennard, Thrombin induces collagen gel contraction partially through PAR1
      activation and PKC-epsilon, Eur. Respir. J. 24 (2004) 918-924]. Here, we further
      report that the delta-isoform of PKC (PKCdelta) is also activated by thrombin and
      involved in the thrombin-mediated augmentation of collagen gel contraction.
      Thrombin (10nM) significantly increased PKCdelta activity (over 5-fold increase
      after 15-30min stimulation) and stimulated phosphorylation of PKCdelta.
      Rottlerin, a PKCdelta inhibitor, completely inhibited activation of PKCdelta and
      partially blocked collagen gel contraction stimulated by thrombin. Similarly,
      PKCdelta-specific siRNA significantly inhibited PKCdelta activation without
      affecting PKCepsilon expression and activation. Furthermore, suppression of
      PKCdelta by siRNA resulted in partial blockade of thrombin-augmented collagen gel
      contraction. These results suggest that thrombin contributes to the tissue
      remodeling in inflammatory airways and lung diseases at least partially through
      both PKCdelta and PKCepsilon signaling.

PMID- 18342629
TI  - RNA-binding proteins and post-transcriptional gene regulation.
AB  - RNAs in cells are associated with RNA-binding proteins (RBPs) to form
      ribonucleoprotein (RNP) complexes. The RBPs influence the structure and
      interactions of the RNAs and play critical roles in their biogenesis, stability,
      function, transport and cellular localization. Eukaryotic cells encode a large
      number of RBPs (thousands in vertebrates), each of which has unique RNA-binding
      activity and protein-protein interaction characteristics. The remarkable
      diversity of RBPs, which appears to have increased during evolution in parallel
      to the increase in the number of introns, allows eukaryotic cells to utilize them
      in an enormous array of combinations giving rise to a unique RNP for each RNA. In
      this short review, we focus on the RBPs that interact with pre-mRNAs and mRNAs
      and discuss their roles in the regulation of post-transcriptional gene
      expression.

PMID- 18342630
TI  - Store-operated Ca(2+) channels and Stromal Interaction Molecule 1 (STIM1) are
      targets for the actions of bile acids on liver cells.
AB  - Cholestasis is a significant contributor to liver pathology and can lead to
      primary sclerosis and liver failure. Cholestatic bile acids induce apoptosis and
      necrosis in hepatocytes but these effects can be partially alleviated by the
      pharmacological application of choleretic bile acids. These actions of bile acids
      on hepatocytes require changes in the release of Ca(2+) from intracellular stores
      and in Ca(2+) entry. However, the nature of the Ca(2+) entry pathway affected is
      not known. We show here using whole cell patch clamp experiments with H4-IIE
      liver cells that taurodeoxycholic acid (TDCA) and other choleretic bile acids
      reversibly activate an inwardly-rectifying current with characteristics similar
      to those of store-operated Ca(2+) channels (SOCs), while lithocholic acid (LCA)
      and other cholestatic bile acids inhibit SOCs. The activation of Ca(2+) entry was
      observed upon direct addition of the bile acid to the incubation medium, whereas
      the inhibition of SOCs required a 12 h pre-incubation. In cells loaded with fura
      2, choleretic bile acids activated a Gd(3+)-inhibitable Ca(2+) entry, while
      cholestatic bile acids inhibited the release of Ca(2+) from intracellular stores
      and Ca(2+) entry induced by 2,5-di-(tert-butyl)-1,4-benzohydro-quinone (DBHQ).
      TDCA and LCA each caused a reversible redistribution of stromal interaction
      molecule 1 (STIM1, the endoplasmic reticulum Ca(2+) sensor required for the
      activation of Ca(2+) release-activated Ca(2+) channels and some other SOCs) to
      puncta, similar to that induced by thapsigargin. Knockdown of Stim1 using siRNA
      caused substantial inhibition of Ca(2+)-entry activated by choleretic bile acids.
      It is concluded that choleretic and cholestatic bile acids activate and inhibit,
      respectively, the previously well-characterised Ca(2+)-selective hepatocyte SOCs
      through mechanisms which involve the bile acid-induced redistribution of STIM1.

PMID- 18342631
TI  - Disulfide bond isomerization in prokaryotes.
AB  - Proteins with multiple cysteine residues often require disulfide isomerization
      reactions before they attain their correct conformation. In prokaryotes this
      reaction is catalyzed mainly by DsbC, a protein that shares many similarities in
      structure and mechanism to the eukaryotic protein disulfide isomerase. This
      review discusses the current knowledge about disulfide isomerization in
      prokaryotes.

PMID- 18342632
TI  - Macrophage mediated protein hydroperoxide formation and lipid oxidation in low
      density lipoprotein are inhibited by the inflammation marker 7,8
      dihydroneopterin.
AB  - The formation of oxidised low density lipoprotein (LDL) within the
      atherosclerotic plaque appears to be a factor in the development of advanced
      atherosclerotic plaques. LDL oxidation is dependent on the balance of oxidants
      and antioxidants within the intima. In addition to producing various oxidants,
      human macrophages release 7,8-dihydroneopterin which in vivo is oxidised to the
      inflammation marker neopterin. Using macrophage-like THP-1 cells and human
      monocyte-derived macrophages, we demonstrate that 7,8-dihydroneopterin is a
      potent inhibitor of cell-mediated LDL oxidation. 7,8-Dihydroneopterin scavenges
      the chain propagating lipid peroxyl radical, inhibiting both lipid and protein
      hydroperoxide formation. A significant amount of the hydroperoxide formed during
      cell-mediated LDL oxidation was protein hydroperoxide. 7,8-Dihydroneopterin
      oxidation to 7,8-dihydroxanthopterin was only observed in the presence of both
      cells and LDL, showing that 7,8-dihydroneopterin had no effect on initiating
      oxidant generation by the cells. 7,8-Dihydroneopterin did not regenerate alpha
      tocopherol but competed with it for the lipid peroxyl radical. Although
      stimulation of both cell types with gamma-interferon failed to produce sufficient
      7,8-dihydroneopterin to inhibit LDL oxidation in tissue culture, analysis of
      advanced atherosclerotic plaque removed from patients showed that total neopterin
      levels could reach low micromolar concentrations. This suggests that 7,8
      dihydroneopterin synthesis by macrophages could play a significant role in the
      development of atherosclerotic plaques.

PMID- 18342633
TI  - Nuclear export of LEI/L-DNase II by Crm1 is essential for cell survival.
AB  - LEI/L-DNase II is the key protein of a caspase-independent pathway activated by
      serine proteases. LEI (Leukocyte elastase inhibitor), L-DNase II precursor, is a
      member of the clade B serpins (also called serpin b1). In its native conformation
      it inhibits several intracellular proteases and has an anti-apoptotic activity.
      Following a metabolic stress and the increase of protease activity in the cell,
      LEI is cleaved and transformed into L-DNase II (LEI-derived DNase II). This
      transformation is due to a conformational modification that exposes a nuclear
      localization signal and an endonuclease active site. In this paper we show that
      LEI can bind the exportin Crm1, and we identify on LEI a nuclear export signal
      involved in the control of LEI/L-DNase II nuclearization in healthy cells. Point
      mutation of this site increases the accumulation of the molecule in the nucleus
      and triggers cell death.

PMID- 18342634
TI  - Senescence and apoptosis in yeast mother cell-specific aging and in higher cells:
      a short review.
AB  - It is our intention to give the reader a short overview of the relationship
      between apoptosis and senescence in yeast mother cell-specific aging. We are
      studying yeast as an aging model because we want to learn something of the basic
      biology of senescence and apoptosis even from a unicellular eukaryotic model
      system, using its unrivalled ease of genetic analysis. Consequently, we will
      discuss also some aspects of apoptosis in metazoa and the relevance of yeast
      apoptosis and aging research for cellular (Hayflick type) and organismic aging of
      multicellular higher organisms. In particular, we will discuss the occurrence and
      relevance of apoptotic phenotypes for the aging process. We want to ask the
      question whether apoptosis (or parts of the apoptotic process) are a possible
      cause of aging or vice versa and want to investigate the role of the cellular
      stress response system in both of these processes. Studying the current
      literature, it appears that little is known for sure in this field and our review
      will therefore be, for a large part, more like a memorandum or a program for
      future research.

PMID- 18342635
TI  - Photosensitizer effects on cancerous cells: a combined study using synchrotron
      infrared and fluorescence microscopies.
AB  - Hypocrellin A (HA), a lipid-soluble peryloquinone derivative, isolated from
      natural fungus sacs of Hypocrella bambusae, has been reported to be a highly
      potential photosensitizer in photodynamic therapy (PDT). It has been studied
      increasingly because of its anticancer activities when irradiated with light. We
      have studied the interaction mechanisms of HA with HeLa cells as a function of
      incubation time. Fluorescence microscopy confirmed that HA localisation is
      limited in the cytoplasm before eventually concentrating in clusters around the
      nucleus. The IR spectra of HA-treated, PDT-treated and control HeLa cells were
      recorded at the ESRF Infrared beamline (ID21). Principal component analysis has
      been used to assess the IR spectral changes between the various HeLa cells
      spectral data sets (The Unscrambler software, CAMO). PCA revealed that there is a
      frequency shift of protein amide I and amide II vibrational bands, indicating
      changes in the protein secondary structures of the HA-treated and PDT-treated
      cancer cells compared to the control cells. In addition, the relative DNA
      intensity in HA-treated cells decreases gradually along the incubation time. The
      use of synchrotron infrared microscopy is shown to be of paramount importance for
      targeting specifically the biochemical modification induced in the cell nucleus.

PMID- 18342636
TI  - A catalytic mechanism that explains a low catalytic activity of serine
      dehydratase like-1 from human cancer cells: crystal structure and site-directed
      mutagenesis studies.
AB  - SDH (l-serine dehydratase, EC 4.3.1.17) is a pyridoxal-5'-phosphate (PLP)
      dependent enzyme that catalyzes dehydration of l-Ser/Thr to yield
      pyruvate/ketobutyrate and ammonia. A SDH isoform (cSDH) found in human cancer
      cell lines has relatively low catalytic activity in comparison with the liver
      enzyme (hSDH). The crystal structure of cSDH has been determined at 2.8 angstroms
      resolution. A PLP is covalently attached to K48 by Schiff-base linkage in the
      active site. The ring nitrogen of PLP is involved in a H-bonding with C309, but
      is apparently not protonated. Twenty-three amino residues that compose the active
      site surfaces were identified. The human and rat liver enzymes (hSDH and rSDH)
      have the same residues, while residues G72, A172, and S228 in cSDH are replaced
      with A66, S166, and A222, respectively, in hSDH. These residues in hSDH and cSDH
      were mutated to make complementary pairs of mutated enzymes, and their kinetic
      parameters were determined. C303 of hSDH and C309 of cSDH which are H-bonding
      partner of the ring nitrogen of PLP were mutated to alanine and their kinetic
      parameters were also determined. The crystal structures and the mutation data
      suggest that having a glycine at residue 72 of cSDH is the major reason for the
      reduction of catalytic activity of cSDH. Changing alanine to glycine at residue
      72 increases the flexibility of the substrate binding-loop (71S(G/A)GN74), so
      that the bound substrate and PLP are not pushed deep into the active cleft.
      Consequently, the proton transfer rate from S(G) of C309 to N1 of the bound PLP
      is decreased, which determines the rate of catalytic reaction.

PMID- 18342637
TI  - Apigenin-induced prostate cancer cell death is initiated by reactive oxygen
      species and p53 activation.
AB  - Apigenin, a plant flavone, potentially activates wild-type p53 and induces
      apoptosis in cancer cells. We conducted detailed studies to understand its
      mechanism of action. Exposure of human prostate cancer 22Rv1 cells, harboring
      wild-type p53, to growth-suppressive concentrations (10-80 microM) of apigenin
      resulted in the stabilization of p53 by phosphorylation on critical serine sites,
      p14ARF-mediated downregulation of MDM2 protein, inhibition of NF-kappaB/p65
      transcriptional activity, and induction of p21/WAF-1 in a dose- and time
      dependent manner. Apigenin at these doses resulted in ROS generation, which was
      accompanied by rapid glutathione depletion, disruption of mitochondrial membrane
      potential, cytosolic release of cytochrome c, and apoptosis. Interestingly, we
      observed accumulation of a p53 fraction to the mitochondria, which was rapid and
      occurred between 1 and 3 h after apigenin treatment. All these effects were
      significantly blocked by pretreatment of cells with the antioxidant N
      acetylcysteine, p53 inhibitor pifithrin-alpha, and enzyme catalase. Apigenin
      mediated p53 activation and apoptosis were further attenuated by p53 antisense
      oligonucleotide treatment. Exposure of cells to apigenin led to a decrease in the
      levels of Bcl-XL and Bcl-2 and increase in Bax, triggering caspase activation.
      Treatment with the caspase inhibitors Z-VAD-FMK and DEVD-CHO partially rescued
      these cells from apigenin-induced apoptosis. In vivo, apigenin administration
      demonstrated p53-mediated induction of apoptosis in 22Rv1 tumors. These results
      indicate that apigenin-induced apoptosis in 22Rv1 cells is initiated by a ROS
      dependent disruption of the mitochondrial membrane potential through
      transcriptional-dependent and -independent p53 pathways.

PMID- 18342638
TI  - Latrunculin B facilitates Shiga toxin 1 transcellular transcytosis across T84
      intestinal epithelial cells.
AB  - Shiga toxins (Stx), released into the intestinal lumen by enterohemorrhagic
      Escherichia coli (EHEC), are major virulence factors responsible for
      gastrointestinal and systemic illnesses. These pathologies are believed to be due
      to the action of the toxins on endothelial cells, which express the Stx receptor,
      the glycosphingolipid Gb3. To reach the endothelial cells, Stx must translocate
      across the intestinal epithelial monolayer. This process is poorly understood. We
      investigated Stx1 movement across the intestinal epithelial T84 cell model and
      the role of actin turnover in this transcytosis. We showed that changes in the
      actin cytoskeleton due to latrunculin B, but not cytochalasin D or
      jasplakinolide, significantly facilitate toxin transcytosis across T84
      monolayers. This trafficking is transcellular and completely inhibited by tannic
      acid, a cell impermeable plasma membrane fixative. This indicates that actin
      turnover could play an important role in Stx1 transcellular transcytosis across
      intestinal epithelium in vitro. Since EHEC attachment to epithelial cells causes
      an actin rearrangement, this finding may be highly relevant to Stx-induced
      disease.

PMID- 18342639
TI  - Metals in Alzheimer's and Parkinson's diseases.
AB  - There has been steadily growing interest in the participation of metal ions
      (especially, zinc, copper, and iron) in neurobiological processes, such as the
      regulation of synaptic transmission. Recent descriptions of the release of zinc
      and copper in the cortical glutamatergic synapse, and influencing the response of
      the NMDA receptor underscore the relevance of understanding the inorganic milieu
      of the synapse to neuroscience. Additionally, major neurodegenerative disorders,
      including Alzheimer's disease and Parkinson's disease, are characterized by
      elevated tissue iron, and miscompartmentalization of copper and zinc (e.g.
      accumulation in amyloid). Increasingly sophisticated medicinal chemistry
      approaches, which correct these metal abnormalities without causing systemic
      disturbance of these essential minerals, are being tested. These small molecules
      show promise of being disease-modifying.

PMID- 18342640
TI  - Octamers and nanoparticles as hemoglobin based blood substitutes.
AB  - Progress in developing a blood substitute is aided by new biotechnologies and a
      better understanding of the circulatory system. For Hb based solutions, there is
      still a debate over the best set of fundamental parameters concerning the oxygen
      affinity which is correlated with the oxidation rate, the cooperativity, the
      transporter size, and of course the final source of material. Genetic engineering
      methods have helped discover novel globins, but not yet the quantity necessary
      for the high demand of blood transfusions. The expanding database of globin
      properties has indicated that certain individual parameters are coupled, such as
      the oxygen affinity and the oxidation rate, indicating that one must accept a
      compromise of the best parameters. After a general introduction of these basic
      criteria, we will focus on two strategies concerning the size of the oxygen
      transporter: Hb octamers, and Hb integrated within a nanoparticle.

PMID- 18342641
TI  - Role of tryptophan-208 residue in cytochrome c oxidation by ascorbate peroxidase
      from Leishmania major-kinetic studies on Trp208Phe mutant and wild type enzyme.
AB  - Ascorbate peroxidase from L. Major (LmAPX) is a functional hybrid between
      cytochrome c peroxidase (CCP) and ascorbate peroxidase (APX). We utilized point
      mutagenesis to investigate if a conserved proximal tryptophan residue (Trp208)
      among Class I peroxidase helps in controlling catalysis. The mutant W208F enzyme
      had no effect on both apparent dissociation constant of the enzyme-cytochrome c
      complex and K(m) value for cytochrome c indicating that cytochrome c binding
      affinity to the enzyme did not alter after mutation. Surprisingly, the mutant was
      1000 times less active than the wild type in cytochrome c oxidation without
      affecting the second order rate constant of compound I formation. Our diode array
      stopped-flow spectral studies showed that the substrate unbound wild type enzyme
      reacts with H(2)O(2) to form compound I (compound II type spectrum), which was
      quite different from that of compound I in W208F mutant as well as horseradish
      peroxidase (HRP). The spectrum of the compound I in wild type LmAPX showed a red
      shift from 409 nm to 420 nm with equal intensity, which was broadly similar to
      those of known Trp radical. In case of compound I for W208F mutant, the peak in
      the Soret region was decreased in heme intensity at 409 nm and was not shifted to
      420 nm suggesting this type of spectrum was similar to that of the known
      porphyrin pi-cation radical. In case of an enzyme-H(2)O(2)-ascorbate system, the
      kinetic for formation and decay of compound I and II of a mutant enzyme was
      almost identical to that of a wild type enzyme. Thus, the results of cytochrome c
      binding, compound I formation rate and activity assay suggested that Trp208 in
      LmAPX was essential for electron transfer from cytochrome c to heme ferryl but
      was not indispensable for ascorbate or guaiacol oxidation.

PMID- 18342643
TI  - Pelvic inflammatory disease attributable to the IUD: modeling risk in West
      Africa.
AB  - BACKGROUND: In Africa, use of the intrauterine device (IUD) is avoided because of
      perceived risk of pelvic inflammatory disease (PID) associated with sexually
      transmitted infections (STI). However, one recent model suggests that the risk of
      PID attributable to the IUD is very low, only 0.15% or less than 1 in 600. STUDY
      DESIGN: Using rates from a 2004 study of cervical STI prevalence in Benin,
      Burkina Faso, Ghana, Guinea, and Mali; we calculate PID risk attributable to the
      IUD in West Africa. RESULTS: Based on 4.4% combined prevalence of chlamydial and
      gonococcal infections, we estimate the risk is 0.075%, or less than 1 in 1,300.
      CONCLUSIONS: In West Africa, PID risk from IUDs is extremely low. This should be
      better communicated to family planning providers in the region who may under
      provide the IUD based on erroneous perceptions of PID risk.

PMID- 18342642
TI  - Quality control of bacterial mRNA decoding and decay.
AB  - Studies in eukaryotes and prokaryotes have revealed that gene expression is not
      only controlled through altering the rate of transcription but also through
      varying rates of translation and mRNA decay. Indeed, the expression level of a
      protein is strongly affected by the steady state level of its mRNA. RNA decay
      can, along with transcription, play an important role in regulating gene
      expression by fine-tuning the steady state level of a given transcript and
      affecting its subsequent decoding during translation. Alterations in mRNA
      stability can in turn have dramatic effects on cell physiology and as a
      consequence the fitness and survival of the organism. Recent evidence suggests
      that mRNA decay can be regulated in response to environmental cues in order to
      enable the organism to adapt to its changing surroundings. Bacteria have evolved
      unique post transcriptional control mechanisms to enact such adaptive responses
      through: 1) general mRNA decay, 2) differential mRNA degradation using small non
      coding RNAs (sRNAs), and 3) selective mRNA degradation using the tmRNA quality
      control system. Here, we review our current understanding of these molecular
      mechanisms, gleaned primarily from studies of the model gram negative organism
      Escherichia coli, that regulate the stability and degradation of normal and
      defective transcripts.

PMID- 18342644
TI  - Over-the-counter access to emergency contraception for teens.
AB  - This synopsis of teens and OTC access is part of a series of briefs on emergency
      contraception, which address the following issues as they relate to EC: Is
      emergency contraception safe? Is emergency contraception effective at preventing
      pregnancy? Does emergency contraception promote sexual risk-taking? Is emergency
      contraception cost-effective? Does emergency contraception cause abortion? The
      full series can be found at http://crhrp.ucsf.edu.

PMID- 18342645
TI  - The relationship between body mass index and unintended pregnancy: results from
      the 2002 National Survey of Family Growth.
AB  - BACKGROUND: The study was conducted to characterize the relationship between body
      mass index (BMI) and unintended pregnancy, contraceptive use patterns, and
      perceived fertility. METHODS: This study employed a cross-sectional, nationally
      representative database (2002 National Survey of Family Growth). Unintended
      pregnancy was compared among BMI groups [normal (<25 m/kg(2)), overweight (25-30
      m/kg(2)) and obese (>30 m/kg(2))]. Analyses also evaluated the association
      between demographic, socioeconomic, behavioral and health-related variables and
      BMI. Multiple logistic regression with adjustment for sampling design was used to
      measure associations of interest. RESULTS: BMI data were available from 6690
      nonpregnant women. Of these, 3600 (53.6%) were normal weight, 1643 (25%) were
      overweight and 1447 (21.4%) were obese. Compared to women with normal BMIs, the
      risk of unintended pregnancy in the last 5 years did not differ among overweight
      [adjusted OR 0.95 (95% CI 0.77-1.17)] or obese [adjusted OR 0.87 (95% CI 0.70
      1.09)] women. There were no differences in contraceptive use patterns or
      perceived fertility among BMI groups. CONCLUSION: Data from the 2002 NSFG do not
      support an association between obesity and unintended pregnancy.

PMID- 18342646
TI  - Longitudinal study of depot medroxyprogesterone acetate (Depo-Provera) effects on
      bone health in adolescents: study design, population characteristics and baseline
      bone mineral density.
AB  - BACKGROUND: This analysis was conducted to assess the baseline data and design
      methodology within an observational longitudinal comparison of use vs. nonuse of
      the injectable (intramuscular) contraceptive depot medroxyprogesterone acetate
      (DMPA-IM) and its effect on bone mass in adolescent women. STUDY DESIGN: A
      prospective, observational, open-label, unmatched-cohort, safety study in females
      aged 11-18 years. Participants either self-selected DMPA-IM (Depo-Provera) 150 mg
      to be administered every 12 weeks for up to 240 weeks with a 120-week post
      treatment follow-up or were nonusers (users of nonhormonal contraception or
      sexually abstinent) who were to be followed up for up to 360 weeks. As each
      participant entered the study, bone mineral density (BMD) was measured by dual
      energy X-ray absorptiometry at the lumbar spine, hip and femoral neck regions,
      along with total body bone mineral content; serum and urine specimens were
      obtained for assay of bone metabolism markers and participants' histories of
      parity and tobacco and alcohol use were obtained. RESULTS: A total of 389
      participants were enrolled: 169 elected to begin DMPA-IM; 26 chose nonhormonal
      methods and 194 were abstinent. The baseline characteristics indicated
      significant disparities between DMPA-IM users and nonusers: compared with the
      nonusers, DMPA-IM users had more advanced chronologic and gynecologic ages, were
      more likely to have smoked, been pregnant and included more blacks. These factors
      would likely influence bone accretion rates independent of DMPA-IM exposure.
      Comparison of participant BMDs with standard reference data revealed that the
      study cohorts did not match reference populations closely enough to make a direct
      between-cohort comparative analysis feasible. CONCLUSIONS: The baseline
      differences in cohort characteristics preclude a meaningful comparison of mean
      BMD changes over time between DMPA-IM users and nonusers cohorts, and comparisons
      of changes in Z-scores between cohorts were also not appropriate. Therefore,
      within-participant BMD decreases from baseline were established as safety
      thresholds, and the proportion of individuals crossing those thresholds on a
      persistent or progressive basis was identified as the revised primary end point.

PMID- 18342647
TI  - Efficacy and safety of 3 mg drospirenone/20 mcg ethinylestradiol oral
      contraceptive administered in 24/4 regimen in the treatment of acne vulgaris: a
      randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: A randomized, double-blind, parallel-group study to investigate the
      efficacy and safety of the 3 mg drospirenone (drsp)/20 mcg ethinylestradiol (EE)
      combined oral contraceptive (COC) administered in a 24/4 regimen (24 active
      tablets and 4 inert tablets per cycle) for the treatment of moderate acne
      vulgaris. STUDY DESIGN: Healthy females (aged 14-45 years old) with moderate
      facial acne were randomized to 3 mg drsp/20 mcg (n=266) or placebo (n=268) for
      six cycles of 28 days. RESULTS: Women who received the 3 mg drsp/20 mcg EE 24/4
      COC had greater reductions from baseline in inflammatory, noninflammatory and
      total lesion counts. The odds of women in the 3 mg drsp/20 mcg EE 24/4 regimen
      COC group having 'clear' or 'almost clear' skin as rated by the investigators at
      end point was about fourfold greater than that in the placebo group (odds ratio
      4.31; 95% CI: 2.11-9.60; p=.001). The 3 mg drsp/20 mcg EE 24/4 regimen COC was
      well tolerated and had a safety profile consistent with low-dose COC use.
      CONCLUSION: The 3 mg drsp/20 mcg EE 24/4 regimen COC was significantly more
      effective than placebo in treating moderate acne vulgaris.

PMID- 18342648
TI  - Hormonal contraceptive discontinuation patterns according to formulation:
      investigation of associations in an administrative claims database.
AB  - BACKGROUND: Hormonal contraceptive use is generally characterized by poor
      adherence and relatively high discontinuation. This study investigated whether
      specific hormonal contraceptive formulations and/or delivery systems might be
      correlated with discontinuation of contraception. STUDY DESIGN: This was a
      retrospective descriptive analysis within a large administrative claims database.
      The sample included women aged 15-40 years with a pharmacy benefit and at least
      one new hormonal contraception prescription during the study period and no
      prescription in the previous 6 months. Filled contraceptive prescriptions were
      grouped into several categories of delivery system, dosage, progestin type and
      monophasic vs. triphasic formulations. In each, a baseline number of women was
      established who filled a first prescription for a contraceptive formulation in
      the specified category. Then, the percentage of these women who filled a
      prescription for a contraceptive in the same category within 3 months' time was
      determined. Continuation or change rates were compared within each group.
      RESULTS: Oral contraceptives (OCs) were the least likely to be discontinued at 3
      months; injectables were the most likely. OC formulations associated with
      increased risk of discontinuation (odds ratios above 1.3 representing a 5% or
      higher increased discontinuation) included very-low-dose (20-25 mcg ethinyl
      estradiol) pills containing norethindrone acetate or norgestimate, as compared to
      a preparation with the same progestin type but with a higher dose of estrogen.
      Desogestrel and norethindrone-containing triphasics were more likely to be
      discontinued than other triphasic progestins. OC formulations with desogestrel
      and norethindrone/norethindrone acetate were more likely than formulations with
      other progestins to be discontinued overall. CONCLUSIONS: This investigation in a
      sample of nearly 250,000 women suggests possible associations between
      discontinuation of hormonal contraception and factors such as estrogen dosing,
      progestin type and changes in dosage during the cycle. Identification of factors
      correlated with contraceptive discontinuation may inform management and improve
      adherence.

PMID- 18342649
TI  - Trends in prescribing patterns of hormonal contraceptives for adolescents.
AB  - BACKGROUND: Little is known regarding how prescribing patterns of hormonal
      contraceptives to adolescents in the United States have changed over time as new
      formulations become available and knowledge of thrombosis risk increases.
      Desogestrel and high-dose estrogen-containing formulations have been associated
      with a higher risk of thrombosis than other methods. STUDY DESIGN: We used the
      National Ambulatory Medical Care/National Hospital Ambulatory Medical Care
      surveys to describe trends in contraception prescriptions for 11- to 21-year-old
      females between 1993 and 2004. RESULTS: The majority of prescriptions arose from
      obstetrics/gynecology clinics. The proportion of desogestrel-containing
      prescriptions was approximately 10% throughout the study period. Ortho Evra
      (transdermal norelgestromin, ethinyl estradiol) and Yasmin (oral drospirenone,
      ethinyl estradiol) accounted for a steadily increasing proportion of
      prescriptions. CONCLUSION: With regard to contraception and thrombosis risk, a
      significant minority of adolescents are prescribed desogestrel-containing
      contraceptives, and a greater number are exposed to higher levels of estrogen
      from transdermal contraception. Future studies are needed to evaluate the
      absolute risk of thrombosis in adolescents using these formulations so clinicians
      have accurate safety information when prescribing to this unique population.

PMID- 18342650
TI  - Contraceptive knowledge and use among low-income Hispanic immigrant women and non
      Hispanic women.
AB  - BACKGROUND: With the rising influx of Hispanics to the United States, there is an
      ongoing need to promote health and wellness care to this non-English-speaking,
      minority population group. Programs, specifically developed to address the unique
      cultural mores of Hispanics, need to focus on increasing knowledge about health
      issues, particularly in the area of reproductive health. A study was conducted in
      Memphis, TN, to examine the differences between low-income Hispanic immigrants'
      and low-income non-Hispanics' (1) contraceptive use; (2) reproduction and
      contraception knowledge; as well as (3) the demographic and knowledge factors
      associated with their choice of contraceptive, in order to better formulate
      successful educational programs for area Hispanics. STUDY DESIGN: A cross
      sectional survey of 226 women, recruited through a federal assistance program in
      Tennessee, was performed over a 5-month period in 2000 to 2001. Women, between
      the ages of 18 and 42, were individually interviewed to learn more about their
      reproduction knowledge and method of contraception. RESULTS: This study found
      that knowledge about reproduction and contraceptive use was significantly lower
      among Hispanics than non-Hispanics. Furthermore, contraceptive use was
      significantly lower among Hispanics than among non-Hispanics. Hispanics were less
      likely to use the oral contraceptive or have a tubal ligation, preferring
      injectable contraceptive. Non-Hispanics, who were more likely to use
      contraceptive methods, were less likely to use injectables, preferring the oral
      contraceptive. Among Hispanics, knowledge about contraceptives, number of
      children and marital status were associated with contraceptive use. Among non
      Hispanics, only education was associated with contraceptive use. CONCLUSION:
      Interventions targeting Hispanic immigrants should be developed to increase their
      knowledge about contraceptive methods.

PMID- 18342651
TI  - Self-described impact of noncompliance among users of a combined hormonal
      contraceptive method.
AB  - BACKGROUND: A number of factors related to the user and the method affect
      contraceptive compliance. STUDY DESIGN: This cross-sectional multicenter study
      was designed to assess self-described impact of noncompliant behavior among
      26,250 typical users of a combined hormonal contraceptive method who consulted
      their physicians for control visits. A self-administered questionnaire was
      completed. RESULTS: Sixty-five percent of women used the pill, 23% the vaginal
      ring and 12% the transdermal patch. Noncompliant behavior (missing/delays in
      taking/application, insertion or removal of the pill/skin patch/vaginal ring) was
      recorded in 71% of pill users, 32% of patch users and 21.6% of vaginal ring users
      (p<.0001). Emergency contraception was requested by 14% of pill users, 11% of
      patch users and 6.3% of ring users. About 40% of women in all groups called or
      visited a physician. Seventy percent of women continued to have active sex life,
      and 60% used an additional contraceptive method. Noncompliant behavior negatively
      affected work activities and/or couple relationships in 10-20% of cases. More
      than 50% of women reported they were worried and about 20% were scared due to
      inconsistent use of the contraceptive method. After filling out the
      questionnaire, 64.7% of pill users continued to prefer the pill, 61.7% of patch
      users preferred the patch and 96.6% of women using the vaginal ring preferred the
      ring. CONCLUSIONS: Noncompliant behavior had noticeable effects on emotional well
      being, prompted request for physicians' advice, and use of emergency
      contraception. Despite recognition of problems associated with inconsistent use,
      women tended to prefer the currently used contraceptive method.

PMID- 18342652
TI  - Communication between parents and their children about sexual health.
AB  - BACKGROUND: Communicating about sex with parents has been shown to influence some
      aspects of sexual behavior in young people. The aim of this study was to
      investigate how comfortable parents and children find this type of discussion and
      to compare parental responses with those of their children. STUDY DESIGN: Self
      completed questionnaires were distributed to 317 teenagers from a state school in
      Edinburgh, Scotland, and to 575 of their parents. The questionnaire was designed
      to appraise relative levels of comfort/discomfort about discussing six sexual
      health topics. Where a parent and their child had both completed questionnaires,
      their responses were compared. RESULTS: Three hundred forty-five parents, 162
      girls and 155 boys, completed questionnaires. Most parents considered themselves
      "comfortable" or "very comfortable" discussing sexual health issues with their
      children, with "boyfriends/girlfriends" as the most comfortable (p< or =.001) and
      "sexual intercourse" the least comfortable topic (p<.0005). However, many
      children stated they "definitely would not" talk to parents (19-65% of
      participants, depending on the topic), citing "embarrassment" as the main reason.
      Eight-six pairs of parent-child responses were matched and compared showing that
      on all topics the least communication occurred between fathers and their
      daughters. CONCLUSIONS: There are clearly barriers to communicating about sexual
      health issues between parents and their children in this population, and this
      seems to stem from reluctance on the part of the children rather than of their
      parents.

PMID- 18342653
TI  - Predictors of delay in each step leading to an abortion.
AB  - BACKGROUND: Approximately 1 out of 10 abortions in the United States occurs in
      the second trimester of pregnancy. This study uses survival analysis to identify
      the factors which delay each step of the process of obtaining an abortion. STUDY
      DESIGN: This is a secondary data analysis of a cross-sectional study
      investigating a sample of 398 women who presented for elective abortion at an
      urban hospital. Respondents completed a survey using an audio-assisted self
      interviewing program and provided a timeline for their process of obtaining an
      abortion. RESULTS: In our analysis, we divided the abortion process into three
      steps ending in three distinct events (first pregnancy test, calling a clinic,
      getting an abortion). Factors associated with delay during the first step include
      obesity [hazard ratio (HR) 0.8, 95% CI 0.6-1.0], abuse of drugs or alcohol (HR
      0.7, 95% CI 0.6-1.0), prior second-trimester abortion (HR 0.6, 95% CI 0.4-0.8)
      and being unsure of last menstrual period (HR 0.6, 95% CI 0.4-0.7) and emotional
      factors such as being in denial (HR 0.8, 95% CI 0.6-1.0) and fear of abortion (HR
      0.7, 95% CI 0.5-1.0). CONCLUSION: This study identified key factors associated
      with delay in obtaining abortion care. Interventions which seek to address these
      factors, especially those factors associated with later pregnancy suspicion and
      testing, may reduce abortion delay and facilitate women obtaining their abortions
      when medical risk and overall cost are lower.

PMID- 18342654
TI  - High prevalence of Mycoplasma genitalium in women presenting for termination of
      pregnancy.
AB  - BACKGROUND: Sexually transmitted infections increase the risk of postoperative
      complications after termination of pregnancy. Mycoplasma genitalium is sexually
      transmitted and associated with adverse clinical outcomes in both males and
      females. The prevalence of M. genitalium is not yet known in New Zealand women or
      among women presenting for termination of pregnancy. STUDY DESIGN: This study
      involved prospective data collection at a public hospital clinic for termination
      of pregnancy. Participants were 300 under 25-year-old women presenting for
      termination of pregnancy. The study aimed to describe the prevalence of M.
      genitalium in women presenting for termination of pregnancy using real-time
      polymerase chain reaction (PCR) testing. Women provided a vaginal swab that was
      sent to the laboratory for PCR detection of M. genitalium. Data collection
      included age, ethnicity, previous pregnancy history, gestational age, procedure
      type, results of STI tests performed on referral for a termination of pregnancy
      (C. trachomatis, N. gonorrhoeae, T. vaginalis and bacterial vaginosis) and use of
      antimicrobials in the past 3 weeks. RESULTS: M. genitalium was detected in 26
      women (8.7%). Rates of infection did not differ significantly by patient
      characteristics such as age, ethnicity or previous pregnancies. Infection with M.
      genitalium was not significantly associated with bacterial vaginosis or C.
      trachomatis infection. CONCLUSIONS: To our knowledge, this is the first
      prospective study designed to determine the prevalence of M. genitalium in women
      presenting for termination of pregnancy. Given the high proportion of cases
      observed in this study, further research is needed to determine the clinical
      significance of M. genitalium in postoperative termination of pregnancy
      complications.

PMID- 18342655
TI  - Investigation of the release behavior of cupric ion for three types of Cu-IUDs
      and indomethacin for medicated Cu-IUD in simulated uterine fluid.
AB  - BACKGROUND: A number of copper-bearing intrauterine devices (Cu-IUDs) are now
      commercially available in China. The release behavior of cupric ion from Cu-IUDs
      is essential to the success of contraception, and the release behavior of
      indomethacin from medicated Cu-IUD is related to its therapeutic effect. STUDY
      DESIGN: In this study, analytical methods were established to investigate the
      release behavior of cupric ion of three existing types of Cu-IUDs and
      indomethacin of one medicated Cu-IUD (Yuangong 365 Cu-IUD). Cu-IUDs were
      incubated in simulated uterine fluid (SUF). The concentrations of cupric ion and
      indomethacin were analyzed by flame atomic absorption spectrometer (FAAS) for 250
      days and UV 752 spectrophotometer for 300 days, respectively. RESULTS: The
      release behavior of cupric ion for three types of Cu-IUDs was biphasic, which
      consisted of the initial burst release and then slow and constant release. The
      release of cupric ion from the medicated Cu-IUD Yuangong 365 showed a zero-order
      process. In vitro release experiment confirmed a sustained release of
      indomethacin from Yuangong 365 and the release was in accordance with the Weibull
      equation. CONCLUSION: The cupric ion release appears to be more constant in the
      medicated Cu-IUD than in the others. In view of the feature of indomethacin
      release from medicated Cu-IUD, it is conjectured that the design of this device
      could be useful to avoid the adverse effects caused by all Cu-IUDs.

PMID- 18342656
TI  - The phosphodiesterase 3 inhibitor ORG 9935 inhibits oocyte maturation in the
      naturally selected dominant follicle in rhesus macaques.
AB  - BACKGROUND: The study was conducted to determine whether the phosphodiesterase
      (PDE) 3 inhibitor ORG 9935 prevents the resumption of meiosis in primate oocytes
      during natural menstrual cycles. STUDY DESIGN: Regularly cycling adult female
      macaques (n=8) were followed during the follicular phase and then started on a 2
      day treatment regimen of human recombinant gonadotropins to control the timing of
      ovulation. Monkeys received no further treatment (controls) or ORG 9935. Oocytes
      were recovered by laparoscopic follicle aspiration 27 h after an ovulatory
      stimulus, cultured in vitro in the absence of inhibitor and inseminated. The
      primary outcome was the meiotic stage of the oocyte. RESULTS: In six ORG 9935
      cycles, five of the recovered oocytes were germinal vesicle (GV)-intact, and one
      exhibited GV breakdown (GVBD). In contrast, all three oocytes that recovered
      during control cycles were GVBD (p<.05). None of the ORG 9935-treated oocytes
      underwent fertilization compared with 2/3 (67%) from controls. CONCLUSIONS: These
      results demonstrate that ORG 9935 blocks resumption of meiosis in the naturally
      selected dominant follicle in primates and suggest that PDE3 inhibitors have
      potential clinical use as contraceptives in women.

PMID- 18342657
TI  - Clinical guidelines. Cervical preparation for surgical abortion from 20 to 24
      weeks' gestation.
AB  - Although less than 2% of abortions in the United States occur after 20 weeks,
      procedures performed at more advanced gestations are associated with increased
      morbidity and mortality. Adequate cervical preparation before dilation and
      evacuation (D&E) at 20 or more weeks' gestation reduces procedural risk. However,
      few clinical trials have included sufficient information on best practices for
      cervical preparation in this gestational age range. For procedures at 20 or more
      weeks' gestation, at least 1 day of cervical preparation is recommended. Evidence
      is less clear that the procedure is faster or safer with the use of either serial
      dilation over more than 1 day or adjuvant misoprostol. Osmotic dilators are
      preferable to misoprostol, but there are insufficient data to support either
      laminaria or Dilapan as the preferred dilator. Fewer Dilapan are needed to gain
      the same amount of dilation as laminaria. The Society of Family Planning
      recommends preoperative cervical preparation before D&E between 20 and 24 weeks.
      Further studies are needed to clarify the best means to prepare the cervix to
      minimize abortion complications and improve outcome in this gestational age
      range.

PMID- 18342658
TI  - Epstein-Barr virus-associated epithelial and mesenchymal neoplasms.
AB  - Epstein-Barr virus (EBV) is a ubiquitous human pathogen that usually maintains a
      harmonious relationship with its host. Rarely, this host-virus balance is
      perturbed, causing a diverse group of malignancies in both immunocompetent and
      immunosuppressed patients. In addition to its role in hematologic malignancies
      (Burkitt lymphoma, subsets of Hodgkin and T-cell lymphomas, posttransplant
      lymphomas), EBV has been implicated in both epithelial (undifferentiated
      nasopharyngeal carcinoma, a subset of gastric adenocarcinomas) and mesenchymal
      (EBV-associated smooth muscle tumor, inflammatory pseudotumor-like follicular
      dendritic cell tumor) neoplasms. This review will focus on EBV-associated
      epithelial and mesenchymal neoplasms.

PMID- 18342659
TI  - An examination of professional and ethical issues in the fellowship application
      process in pathology.
AB  - Approximately 34 medical specialty and subspecialty fellowship programs in the
      United States have formalized the application process through the National
      Resident Matching Program. This approach sets standards for the application
      process, offers a formalized match similar to that for residency programs,
      functions within a specific timeline, and establishes binding rules of behavior
      for both applicants and programs. For fellowship programs that operate outside
      the National Resident Matching Program, such as those in pathology, no published
      guidelines exist to help programs and applicants address the many questions and
      problems that can arise. As a result, programs are free to set their own
      timelines for interviews, application requirements, contract negotiations and
      finalizations, and other details. Consequently, applicants often feel pressured
      to apply earlier and earlier in their residency for competitive fellowship
      programs, are often required to fill out multiple unique applications, may feel
      no "loyalty" toward honoring an acceptance without a contract, and often feel
      disenfranchised by the whole process. This article addresses professional and
      ethical aspects of the current application process and offers possible solutions
      for improving it.

PMID- 18342660
TI  - A Web-based database for pathology faculty effort reporting.
AB  - To ensure appropriate mission-based budgeting and equitable distribution of funds
      for faculty salaries, our compensation committee developed a pathology-specific
      effort reporting database. Principles included the following: (1) measurement
      should be done by web-based databases; (2) most entry should be done by
      departmental administration or be relational to other databases; (3) data entry
      categories should be aligned with funding streams; and (4) units of effort should
      be equal across categories of effort (service, teaching, research). MySQL was
      used for all data transactions (http://dev.mysql.com/downloads), and scripts were
      constructed using PERL (http://www.perl.org). Data are accessed with forms that
      correspond to fields in the database. The committee's work resulted in a novel
      database using pathology value units (PVUs) as a standard quantitative measure of
      effort for activities in an academic pathology department. The most common
      calculation was to estimate the number of hours required for a specific task,
      divide by 2080 hours (a Medicare year) and then multiply by 100. Other methods
      included assigning a baseline PVU for program, laboratory, or course directorship
      with an increment for each student or staff in that unit. With these methods, a
      faculty member should acquire approximately 100 PVUs. Some outcomes include (1)
      plotting PVUs versus salary to identify outliers for salary correction, (2)
      quantifying effort in activities outside the department, (3) documenting salary
      expenditure for unfunded research, (4) evaluating salary equity by plotting PVUs
      versus salary by sex, and (5) aggregating data by category of effort for mission
      based budgeting and long-term planning.

PMID- 18342661
TI  - Immunohistochemical expression of folate receptor alpha in colorectal carcinoma:
      patterns and biological significance.
AB  - Folate receptor alpha (FRalpha) has emerged as a potential cancer therapy target
      with several folate-linked therapeutic agents currently undergoing clinical
      trials. In addition, FRalpha expression in tumors may offer prognostic
      significance. Most studies on FRalpha expression used reverse transcriptase
      polymerase chain reaction or cytofluorimetric assays. The applicability of such
      methods to paraffin-embedded tissues is limited. The aims of this study were to
      assess the feasibility of immunohistochemistry in detecting FRalpha expression
      and to assess the patterns and clinical significance of FRalpha expression in
      colorectal tissues. We used tissue microarrays containing 152 normal colorectal
      mucosa samples, 42 adenomas, 177 primary, and 52 metastatic colorectal
      carcinomas. Our results showed that staining for FRalpha on colorectal tissues
      was simple and easy to read. FRalpha positivity was more frequent in carcinomas
      (33% in primaries and 44% in metastases) than in normal mucosa or adenoma (7% in
      both) (P < .001). Positive staining in primary carcinomas correlated with younger
      age (n = 130) (P = .008), presence of distant metastasis (n = 130) (P = .043),
      and non-high-frequency microsatellite instability status (as detected by the
      standard polymerase chain reaction method using the 5 National Cancer Institute
      recommended markers) (n = 77) (P = .006). Positive staining in primary carcinomas
      also correlated with a worse 5-year disease-specific survival (P = .04) on
      univariate but not multivariate analysis. Thus, our data show that there is
      selective expression of FRalpha in some colorectal cancers, providing a
      foundation for investigating the use of folate conjugates for imaging and therapy
      of colorectal tumors. Furthermore, our results suggest that a possible
      association exists between FRalpha expression and the microsatellite instability
      status in colorectal carcinoma. The significance of such an association as well
      as the prognostic value of FRalpha expression deserves further exploration.

PMID- 18342662
TI  - Calling time on young people's alcohol consumption.

PMID- 18342663
TI  - Can DFID help reform the World Bank?

PMID- 18342664
TI  - More options to screen for colorectal cancer.

PMID- 18342665
TI  - Biodegradable drug-eluting stents: promises and pitfalls.

PMID- 18342666
TI  - Antibiotics for sinusitis-like symptoms in primary care.

PMID- 18342667
TI  - Heart disease in Soweto: facing a triple threat.

PMID- 18342668
TI  - Non-laboratory-based prediction of cardiovascular risk.

PMID- 18342669
TI  - Maternal deaths and vulnerable migrants.

PMID- 18342670
TI  - Prioritisation of routine vaccines: a mistake for the USA.

PMID- 18342671
TI  - Decision time for pancreatic islet-cell transplantation.

PMID- 18342675
TI  - The ethics of non-inferiority trials.

PMID- 18342676
TI  - The ethics of non-inferiority trials.

PMID- 18342677
TI  - The ethics of non-inferiority trials.

PMID- 18342678
TI  - The ethics of non-inferiority trials.

PMID- 18342679
TI  - The ethics of non-inferiority trials.

PMID- 18342681
TI  - Survival rates in very preterm babies in England and Wales.

PMID- 18342682
TI  - Now voyager sail thou forth to seek and find.

PMID- 18342683
TI  - Neonatal euthanasia in France.

PMID- 18342684
TI  - A bioabsorbable everolimus-eluting coronary stent system for patients with single
      de-novo coronary artery lesions (ABSORB): a prospective open-label trial.
AB  - BACKGROUND: A fully bioabsorbable drug-eluting coronary stent that scaffolds the
      vessel wall when needed and then disappears once the acute recoil and
      constrictive remodelling processes have subsided has theoretical advantages. The
      bioasorbable everolimus-eluting stent (BVS) has a backbone of poly-L-lactic acid
      that provides the support and a coating of poly-D,L-lactic acid that contains and
      controls the release of the antiproliferative agent everolimus. We assessed the
      feasibility and safety of this BVS stent. METHODS: In this prospective, open
      label study we enrolled 30 patients who had either stable, unstable, or silent
      ischaemia and a single de-novo lesion that was suitable for treatment with a
      single 3.0 x 12 mm or 3.0 x 18 mm stent. Patients were enrolled from four
      academic hospitals in Auckland, Rotterdam, Krakow, and Skejby. The composite
      endpoint was cardiac death, myocardial infarction, and ischaemia-driven target
      lesion revascularisation. Angiographic endpoints were available for 26 patients
      and intravascular-ultrasound endpoints for 24 patients. Clinical endpoints were
      assessed in all 30 patients at 6 and 12 months. In a subset of 13 patients,
      optical coherence tomography was undertaken at baseline and follow-up. Analysis
      was by intention to treat. This study is registered with ClinicalTrials.gov,
      number NCT00300131. FINDINGS: Procedural success was 100% (30/30 patients), and
      device success 94% (29/31 attempts at implantation of the stent). At 1 year, the
      rate of major adverse cardiac events was 3.3%, with only one patient having a non
      Q wave myocardial infarction and no target lesion revascularisations. No late
      stent thromboses were recorded. At 6-month follow-up, the angiographic in-stent
      late loss was 0.44 (0.35) mm and was mainly due to a mild reduction of the stent
      area (-11.8%) as measured by intravascular ultrasound. The neointimal area was
      small (0.30 [SD 0.44] mm2), with a minimal area obstruction of 5.5%.
      INTERPRETATION: This study shows the feasibility of implantation of the
      bioabsorbable everolimus-eluting stent, with an acceptable in-stent late loss,
      minimal intrastent neointimal hyperplasia, and a low stent area obstruction.
      FUNDING: Abbott Vascular.

PMID- 18342685
TI  - Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta
      analysis of individual patient data.
AB  - BACKGROUND: Primary-care physicians continue to overprescribe antibiotics for
      acute rhinosinusitis because distinction between viral and bacterial sinus
      infection is difficult. We undertook a meta-analysis of randomised trials based
      on individual patients' data to assess whether common signs and symptoms can be
      used to identify a subgroup of patients who benefit from antibiotics. METHODS: We
      identified suitable trials--in which adult patients with rhinosinusitis-like
      complaints were randomly assigned to treatment with an antibiotic or a placebo-
      by searching the Cochrane Central Register of Controlled Trials, Medline, and
      Embase, and reference lists of reports describing such trials. Individual
      patients' data from 2547 adults in nine trials were checked and re-analysed. We
      assessed the overall effect of antibiotic treatment and the prognostic value of
      common signs and symptoms by the number needed to treat (NNT) with antibiotics to
      cure one additional patient. FINDINGS: 15 patients with rhinosinusitis-like
      complaints would have to be given antibiotics before an additional patient was
      cured (95% CI NNT[benefit] 7 to NNT[harm] 190). Patients with purulent discharge
      in the pharynx took longer to cure than those without this sign; the NNT was 8
      patients with this sign before one additional patient was cured (95% CI
      NNT[benefit] 4 to NNT[harm] 47). Patients who were older, reported symptoms for
      longer, or reported more severe symptoms also took longer to cure but were no
      more likely to benefit from antibiotics than other patients. INTERPRETATION:
      Common clinical signs and symptoms cannot identify patients with rhinosinusitis
      for whom treatment is clearly justified. Antibiotics are not justified even if a
      patient reports symptoms for longer than 7-10 days.

PMID- 18342686
TI  - Spectrum of heart disease and risk factors in a black urban population in South
      Africa (the Heart of Soweto Study): a cohort study.
AB  - BACKGROUND: The Heart of Soweto Study aims to increase our understanding of the
      characteristics and burden imposed by heart disease in an urban African community
      in probable epidemiological transition. We aimed to investigate the clinical
      range of disorders related to cardiovascular disease in patients presenting for
      the first time to a tertiary-care centre. METHODS: From Jan 1 to Dec 31, 2006, we
      recorded data for 4162 patients with confirmed cases of cardiovascular disease
      (1593 newly diagnosed and 2569 previously diagnosed and under treatment) who
      attended the cardiology unit at the Chris Hani Baragwanath Hospital in Soweto,
      South Africa. We developed a prospectively designed registry and gathered
      detailed clinical data relating to the presentation, investigations, and
      treatment of all 1593 patients with newly diagnosed cardiovascular disease.
      FINDINGS: Most patients were black Africans (n=1359 [85%]), and the study
      population contained more women (n=939 [59%]) than men. Women were slightly
      younger than were men (mean 53 [SD 16] years vs 55 [15] years; p=0.031), with 399
      (25%) patients younger than 40 years. Heart failure was the most common primary
      diagnosis (704 cases, 44% of total). Moderate to severe systolic dysfunction was
      evident in 415 (53%) of 844 identified cases of heart failure, 577 (68%) of which
      were attributable to dilated cardiomyopathy or hypertensive heart disease, or
      both. Black Africans were more likely to be diagnosed with heart failure than
      were the rest of the cohort (739 [54%] vs 105 [45%]; odds ratio [OR] 1.46, 95% CI
      1.11-1.94; p=0.009) but were less likely to be diagnosed with coronary artery
      disease (77 [6%] vs 88 [38%]; OR 0.10, 0.07-0.14; p<0.0001). Prevalence of
      cardiovascular risk factors was very high, with 897 (56%) patients diagnosed with
      hypertension (190 [44%] of whom were also obese). Only 209 (13%) patients had no
      identifiable risk factors, whereas 933 (59%) had several risk factors.
      INTERPRETATION: We noted many threats to the present and future cardiac health of
      Soweto, including a high prevalence of modifiable risk factors for
      atherosclerotic disease and a combination of infectious and non-communicable
      forms of heart disease, with late clinical presentations. Overall, our findings
      provide strong evidence that epidemiological transition in Soweto, South Africa
      has broadened the complexity and spectrum of heart disease in this community.
      This registry will enable continued monitoring of the range of heart disease.

PMID- 18342687
TI  - Laboratory-based versus non-laboratory-based method for assessment of
      cardiovascular disease risk: the NHANES I Follow-up Study cohort.
AB  - BACKGROUND: Around 80% of all cardiovascular deaths occur in developing
      countries. Assessment of those patients at high risk is an important strategy for
      prevention. Since developing countries have limited resources for prevention
      strategies that require laboratory testing, we assessed if a risk prediction
      method that did not require any laboratory tests could be as accurate as one
      requiring laboratory information. METHODS: The National Health and Nutrition
      Examination Survey (NHANES) was a prospective cohort study of 14 407 US
      participants aged between 25-74 years at the time they were first examined
      (between 1971 and 1975). Our follow-up study population included participants
      with complete information on these surveys who did not report a history of
      cardiovascular disease (myocardial infarction, heart failure, stroke, angina) or
      cancer, yielding an analysis dataset N=6186. We compared how well either method
      could predict first-time fatal and non-fatal cardiovascular disease events in
      this cohort. For the laboratory-based model, which required blood testing, we
      used standard risk factors to assess risk of cardiovascular disease: age,
      systolic blood pressure, smoking status, total cholesterol, reported diabetes
      status, and current treatment for hypertension. For the non-laboratory-based
      model, we substituted body-mass index for cholesterol. FINDINGS: In the cohort of
      6186, there were 1529 first-time cardiovascular events and 578 (38%) deaths due
      to cardiovascular disease over 21 years. In women, the laboratory-based model was
      useful for predicting events, with a c statistic of 0.829. The c statistic of the
      non-laboratory-based model was 0.831. In men, the results were similar (0.784 for
      the laboratory-based model and 0.783 for the non-laboratory-based model). Results
      were similar between the laboratory-based and non-laboratory-based models in both
      men and women when restricted to fatal events only. INTERPRETATION: A method that
      uses non-laboratory-based risk factors predicted cardiovascular events as
      accurately as one that relied on laboratory-based values. This approach could
      simplify risk assessment in situations where laboratory testing is inconvenient
      or unavailable.

PMID- 18342688
TI  - Mumps.
AB  - Mumps is a common childhood infection caused by the mumps virus. The hallmark of
      infection is swelling of the parotid gland. Aseptic meningitis and encephalitis
      are common complications of mumps together with orchitis and oophoritis, which
      can arise in adult men and women, respectively; other complications include
      deafness and pancreatitis. Clinical diagnosis can be based on the classic parotid
      swelling; however, this feature is not present in all cases of mumps and can also
      occur in various other disorders. Laboratory diagnosis is based on isolation of
      virus, detection of viral nucleic acid, or serological confirmation (generally
      presence of IgM mumps antibodies). Mumps is vaccine-preventable, and one dose of
      mumps vaccine is about 80% effective against the disease. Routine vaccination has
      proven highly effective in reducing the incidence of mumps, and is presently used
      by most developed countries; however, there have been outbreaks of disease in
      vaccinated populations. In 2005, a large epidemic peaked in the UK, and in 2006
      the American midwest had several outbreaks. In both countries, the largest
      proportion of cases was in young adults. In the UK, susceptible cohorts too old
      to have been vaccinated and too young to have been exposed to natural infections
      were the primary cause of the mumps epidemic. In the USA, effectiveness and
      uptake in combination appear not to have been sufficient to obtain herd immunity
      for mumps in populations such as college students.

PMID- 18342689
TI  - Mycosis fungoides and Sezary syndrome.
AB  - Mycosis fungoides and Sezary syndrome are the most common of the cutaneous T-cell
      lymphomas, which are a heterogeneous group of neoplasms that affect the skin as a
      primary site. Although the aetiologies of mycosis fungoides and Sezary syndrome
      are unknown, important insights have been gained in the immunological and genetic
      perturbations that are associated with these diseases. Unlike some B-cell
      lymphomas, cutaneous T-cell lymphomas as a group are rarely if ever curable and
      hence need chronic-disease management. New approaches to treatments are being
      investigated and include biological and cytotoxic drugs, phototherapy, and
      monoclonal antibodies that are directed towards novel molecular targets. New
      molecular technologies such as complementary-DNA microarray have the potential to
      increase the accuracy of diagnosis and provide important prognostic information.
      Treatments can be combined to greatly improve clinical outcome without
      substantially increasing toxic effects in advanced disease that is otherwise
      difficult to treat. Although present treatment strategies are generally not
      curative, there is hope that experimental treatments, particularly immunotherapy,
      might eventually reverse or suppress the abnormalities of mycosis fungoides and
      Sezary syndrome to the point at which they become non-life-threatening, chronic
      diseases.

PMID- 18342690
TI  - Blood, semen, and an innocent man.

PMID- 18342691
TI  - Steps Forward in Pompe Disease. Abstracts of the 2nd European Symposium. Nice,
      France. November 9-10, 2007.

PMID- 18342707
TI  - A comment on "Kavanagh M, Shams K. Botulinum toxin type A by iontophoresis for
      primary palmar hyperhidrosis".

PMID- 18342708
TI  - Chemotherapeutic agents and the skin: An update.
AB  - Chemotherapeutic agents give rise to numerous well described adverse effects that
      may affect the skin, hair, mucous membranes, or nails. The mucocutaneous effects
      of longstanding agents have been extensively studied and reviewed. Over the last
      2 decades, a number of new molecular entities for the treatment of cancer have
      been approved by the United States Food and Drug Administration (FDA). This
      article reviews the cutaneous toxicity patterns of these agents. It also reviews
      one drug that has not received FDA approval but is in use outside the United
      States and is important dermatologically. Particular emphasis is placed on the
      novel signal transduction inhibitors as well as on newer literature pertaining to
      previously described reactions. LEARNING OBJECTIVES: At the completion of this
      learning activity, participants should able to list the newer chemotherapeutic
      agents that possess significant mucocutaneous side effects and describe the range
      of reactions that are seen with each drug. In addition, they should be able to
      formulate appropriate management strategies for these reactions.

PMID- 18342709
TI  - Primary cutaneous adenoid cystic carcinoma.
AB  - Primary cutaneous adenoid cystic carcinoma is a rare, slow-growing malignancy
      first described by Boggio in 1975. This tumor characteristically consists of
      basophilic cells with a distinct adenoid or cribriform pattern in the mid to deep
      reticular dermis. Modified myoepithelial cells with prominent basement membrane
      material often surround true lumina. Definitive diagnosis relies on the
      characteristic histologic features and the exclusion of metastatic disease. We
      describe two patients who presented with painful papules of the scalp and were
      successfully treated with wide local excision.

PMID- 18342710
TI  - Epidermal growth factor receptor inhibitors and hair.
AB  - Dialogues in Dermatology, a monthly audio program from the American Academy of
      Dermatology, contains discussions between dermatologists on timely topics.
      Commentaries from Dialogues Editor-in-Chief Warren R. Heymann, MD, are provided
      after each discussion as a topic summary and are provided here as a special
      service to readers of the Journal of the American Academy of Dermatology.

PMID- 18342711
TI  - Sclerodermiform linear lupus erythematosus: A distinct entity or coexistence of
      two autoimmune diseases?
AB  - The coexistence of features of chronic cutaneous lupus erythematosus and
      scleroderma in the same skin lesions is very infrequent and has only been
      reported in 3 patients. This exceedingly rare condition has been named
      "sclerodermiform linear lupus erythematosus." We describe a new case of this
      dermatosis. Although the cause remains obscure, possible explanations include
      mosaicism following Blaschko's lines or the transfer of microchimerisms that
      mount a chronic graft-versus-host-like reaction. We suggest that these features
      may be a distinct clinicopathologic disorder characterized by an initial
      lichenoid reaction followed by the production of excessive, abnormal connective
      tissue.

PMID- 18342712
TI  - Multiple papules and nodules on the face and neck caused by the larvae of an
      unknown nematode: A noncreeping type eruption.
AB  - Cutaneous larva migrans is caused by various nematodes. Skin manifestations may
      include superficial or creeping eruptions, folliculitis, and migratory
      subcutaneous nodules. We report a 52-year-old man with asymptomatic, multiple
      eruptive papules and nodules on the face and neck caused by the larvae of an
      unknown nematode. The patient never had any creeping or migratory eruptions. Our
      case is very unusual and differs from previously reported cases of cutaneous
      larva migrans.

PMID- 18342713
TI  - IgM-lambda paraproteinemia with associated cutaneous lymphoplasmacytic infiltrate
      in a patient who meets diagnostic criteria for POEMS syndrome.
AB  - POEMS is a rare multisystem paraneoplastic syndrome featuring polyneuropathy,
      organomegaly, endocrinopathy, a monoclonal protein, and skin changes. In the
      relatively few reported biopsies of POEMS-associated cutaneous hyperpigmentation,
      the most common skin finding seen in patients with the disorder, only a non
      specific inflammatory infiltrate has been demonstrated histologically. We present
      the case of a 79-year-old man with polyneuropathy, autoimmune thyroiditis,
      pancytopenia, and a history of lymphadenopathy who presented to the inpatient
      dermatology service with cutaneous hyperpigmentation. A skin biopsy of a
      hyperpigmented area showed a cutaneous lymphoplasmacytic infiltrate, prompting
      further investigation. A monoclonal IgM-lambda paraprotein was subsequently
      identified, leading to administration of combination chemotherapy for a diagnosis
      of POEMS syndrome. The novel finding of a lymphoplasmacytic infiltrate in POEMS
      associated hyperpigmentation suggests a diagnostic role for skin biopsy in these
      patients.

PMID- 18342714
TI  - Cutaneous plasmablastic lymphoma.
AB  - Plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma occurring in
      immunocompromised individuals. Multiple organ sites may be involved; however,
      cutaneous involvement has been rarely reported in the medical literature. To
      date, there have been only 7 reports of cutaneous plasmablastic lymphoma without
      systemic involvement. We report a case of isolated cutaneous plasmablastic
      lymphoma occurring in an HIV-positive man with more than 10 years of follow-up.

PMID- 18342715
TI  - Pagetoid reticulosis in a 5-year-old boy.
AB  - We present a rare case of pagetoid reticulosis arising in a 5-year-old white boy.
      He had a history of a large chronic erythematous, scaly patch on his left buttock
      that had shown intermittent partial response to a topical antifungal medication.
      A punch biopsy specimen revealed dramatic epidermal hyperplasia, with
      parakeratosis and prominent exocytosis of single and clustered mononuclear cells
      (Pautrier's microabscesses) into the epidermis. Some of these exhibited
      hyperchromatic nuclei with irregular contours. They stained prominently for CD3,
      CD4, and CD8, with a predominance of CD8(+) cells. T-cell receptor gene
      rearrangement by polymerase chain reaction was negative for a clonal process on a
      second biopsy specimen that was nondiagnostic on routine sections. Pagetoid
      reticulosis is an indolent, unilesional variant of mycosis fungoides, in which
      the atypical T cells may express a CD4(-)/CD8(+) phenotype. This is in contrast
      to primary cutaneous epidermotropic CD8(+) cytotoxic T-cell lymphoma, which is
      often very aggressive with a poor outcome. Pagetoid reticulosis is exceedingly
      rare in children and adolescents. Two features predict a benign course in this 5
      year-old child: the unilesional clinical presentation and the CD8 predominance of
      the epidermal lymphocytes.

PMID- 18342716
TI  - Single-plaque vegetating bromoderma.
AB  - Potassium bromide is still in use for the treatment of multidrug-resistant
      seizures. It is a known cause of severe drug-induced skin disorders. The clinical
      presentation of bromoderma may be similar to that of pyoderma gangrenosum when
      occurring with a single lesion. The case of a young girl with a single vegetating
      plaque of bromoderma on the leg is reported. The presence of pustules at the
      periphery of the plaque provides the clinical clue to the diagnosis.

PMID- 18342717
TI  - Abortive or minimal-growth hemangiomas: Immunohistochemical evidence that they
      represent true infantile hemangiomas.
AB  - BACKGROUND: Infantile hemangiomas have a characteristic natural history of rapid
      proliferation in the first weeks of life followed by spontaneous involution. At
      birth, they may be present as a precursor lesion. Sometimes one may see precursor
      lesions that never undergo a growth phase or that undergo minimal growth. It is
      unclear the exact nature of these precursor-like lesions. OBJECTIVE: We sought to
      describe the morphology and histopathology of these precursor-like lesions.
      METHODS: We describe 4 patients with macules resembling precursor lesions of
      hemangiomas that did not show proliferation phase or minimal growth. The
      histopathologic and immunohistochemical study with glucose transporter-1 was
      performed in all of these cases. RESULTS: The skin biopsy specimen showed
      superficial ectatic vessels that reacted with anti-glucose transporter-1
      antibodies. All skin biopsy specimens exhibited capillary lobules in papillary
      dermis and, in two of them, in the reticular dermis and subcutis. LIMITATIONS:
      This text is limited by the number of cases reported. CONCLUSIONS: Precursor
      lesions of hemangioma that do not show proliferation phase or minimal growth
      represent, in the view of glucose transporter-1 immunoreactivity, true
      hemangiomas of infancy with an aborted or arrested growth cycle.

PMID- 18342718
TI  - Reactive eccrine syringofibroadenoma arising in peristomal skin: An unusual
      presentation of a rare lesion.
AB  - We report the third case of eccrine syringofibroadenoma (ESFA) arising in
      peristomal skin. A 55-year-old man presented with a 15- x 10-cm pale pink
      verrucous, exophytic, intermittently tender plaque involving his ileostomy site.
      He had undergone proctocolectomy with ileostomy creation 33 years prior for
      ulcerative colitis. The clinical differential diagnosis included granulomatous
      dermatitis, infection (fungus or atypical mycobacterium), or neoplasm. A punch
      biopsy specimen was performed and showed ESFA. Although ESFA is considered to be
      benign, recent reports have demonstrated an association of ESFA with malignancy
      or malignant transformation of ESFA. Furthermore, ESFA and reported cases of
      ileostomy carcinoma share similar clinical symptoms at presentation including
      pain, irritation, ulceration, bleeding, and the presence of a fungating mass. The
      lesion was, therefore, excised in toto and the excisional specimen showed no
      evidence of malignancy. We speculate that ESFA is a reaction to chronic
      irritation and, analogous to other long-standing reactive processes such as
      lichen sclerosis or burn scar ulcers, may be associated with malignant
      transformation. Because of this possibility and the clinical overlap with
      ileostomy carcinoma, peristomal ESFA should be treated with complete excision. If
      it is not amenable to complete excision because of lesion size or anatomic
      complexity, generous sampling and close clinical follow-up are recommended.

PMID- 18342719
TI  - Macrocephaly-cutis marmorata telangiectatica congenita: A case report and review
      of salient features.
AB  - Macrocephaly-cutis marmorata telangiectatica congenita is a recently recognized
      syndrome described mainly in the genetics literature. However, children with
      macrocephaly-cutis marmorata telangiectatica congenita are likely to present
      first to a dermatologist, with generalized cutis marmorata telangiectatica
      congenita as the main feature. These children are at risk of neurologic
      abnormalities and life-threatening complications. Therefore it is important for
      dermatologists to recognize this syndrome to monitor these children for potential
      complications. We report the case of a 2-year-old boy with macrocephaly-cutis
      marmorata telangiectatica congenita in association with dysmorphic facies,
      seizures, and facial and limb asymmetry, and we review the salient features of
      this syndrome.

PMID- 18342720
TI  - Transforming growth factor-beta overexpression in cutaneous extramedullary
      hematopoiesis of a patient with myelodysplastic syndrome associated with
      myelofibrosis.
AB  - Extramedullary hematopoiesis (EMH) is a relatively rare, but well-documented,
      manifestation of chronic myeloproliferative disorders. Microscopically, foci of
      EMH consist of erythroid and myeloid precursors intermixed with megakaryocytes.
      It typically occurs in the spleen and liver, but very occasionally manifests as
      cutaneous EMH. We report a 76-year-old Japanese man with cutaneous EMH arising
      from myelodysplastic syndrome associated with myelofibrosis. His cutaneous
      manifestations showed multiple skin-colored firm nodules over the head, trunk,
      and extremities. We detected high plasma levels of transforming growth factor
      (TGF)-beta1 in our patient. Immunohistochemical analysis of the skin biopsy
      sample revealed TGF-beta1 overexpression in immature hematopoietic cells and
      dermal fibroblasts within the cutaneous EMH mass of the dermis. These findings
      suggest that TGF-beta could play some role in the onset of cutaneous EMH. Five
      months after his first visit to our dermatologic clinic, the patient developed
      bone-marrow failure and died. Based on our observations, accelerated malignancy
      in the bone marrow should be considered in any patient with cutaneous EMH. It is
      presumed that TGF-beta released from hematopoietic cells within the cutaneous EMH
      play a critical role in the activation of hematologic malignancy.

PMID- 18342721
TI  - Dystrophic calcinosis cutis in pseudoxanthoma elasticum.
AB  - Pseudoxanthoma elasticum (PXE) is a genetic disorder in which elastic fibers
      become calcified with prominent cutaneous, ocular, and cardiovascular features.
      Calcinosis cutis is an acquired disorder of calcium deposition in cutaneous
      tissues that occurs as one of the following forms: dystrophic, metastatic,
      idiopathic, and iatrogenic. We report a case of a woman with PXE who developed
      widespread dystrophic calcinosis cutis in areas affected by PXE. Although tumoral
      calcification and nephrolithiasis have been reported in patients with PXE, only
      one other case in the English-language literature of PXE and calcinosis cutis has
      been reported and this case was characterized by small, milia-like papules on the
      front of the neck, without significant discomfort, whereas our patient had
      widespread involvement that was very painful and pruritic. On 6-month follow-up,
      this patient had only mild improvement after treatment with an anti-itch lotion
      and aluminum hydroxide, with which she was noncompliant.

PMID- 18342722
TI  - Targeted therapy of oral hairy leukoplakia with gentian violet.
AB  - Oral hairy leukoplakia (OHL) is a common oral manifestation of HIV infection.
      Clinically, these lesions appear as white plaques on the edges of the tongue.
      Pathophysiologically, these lesions occur because of infection of oral epithelium
      with Epstein-Barr virus (EBV). No universally effective therapy exists for OHL.
      We have previously shown that EBV infection and EBV viral products induce the
      generation of reactive oxygen. We have also demonstrated that the Food and Drug
      Administration-approved over-the-counter medication gentian violet is a potent
      inhibitor of reactive oxygen species. We thus chose to treat a patient with
      biopsy-proven OHL with topical gentian violet. Gentian violet solution was
      applied topically to the tongue of a patient with OHL. Complete clinical
      resolution was noted after three treatments. Treatment with topical gentian
      violet resulted in resolution of the lesions. Further studies with larger numbers
      of patients are required. The application of gentian violet can be used as a
      method to OHL treatment. Gentian violet is an inexpensive and safe therapy and,
      given that it inhibits reactive oxygen, this old therapy is now a targeted novel
      therapy.

PMID- 18342723
TI  - Neoplasia-induced autoimmunity encompasses a spectrum of changes.

PMID- 18342724
TI  - Disclosure does not absolve!

PMID- 18342725
TI  - Videodermoscopy of the hyponychium in nail bed psoriasis.

PMID- 18342726
TI  - The need for leadership: How can we better train the next generation of
      dermatologists?

PMID- 18342727
TI  - Technical tips for vascular and endovascular surgeons. Introduction.

PMID- 18342728
TI  - Technical tips for carotid angioplasty and stenting.
AB  - Angioplasty and stenting of the carotid artery has become an accepted procedure
      in properly selected patients with carotid artery stenosis. The potential for
      devastating neurologic complications and significant hemodynamic changes
      separates endovascular treatment of the carotid artery from other percutaneous
      peripheral vascular procedures. In this article, the technique for carotid artery
      angioplasty and stenting is described and the strategies for management of the
      hemodynamic changes occuring with carotid stenting are reviewed.

PMID- 18342729
TI  - Technical tips for thoracic aortic endografting.
AB  - Thoracic aortic endografting is proving to be extremely useful for correcting a
      variety of lesions with few complications. Endovascular intervention avoids
      sternotomy or thoracotomy, the use of chest tubes, respirators, and general
      anesthesia, and limits blood loss. Compared with traditional open surgery,
      complications such as paraplegia, renal failure, and cardiac and pulmonary
      difficulties are minimized; hospital and rehabilitation times are also reduced.
      Selection of patients on the basis of favorable anatomy and pathology for a
      specific device is critical to procedural success. In some cases, a
      retroperitoneal conduit may be useful. In addition, left carotid-subclavian
      bypass or a transposition of the left subclavian artery to the left common
      carotid artery may be necessary before endografting, and spinal cord fluid
      drainage may be important when there is potential for cord ischemia.

PMID- 18342730
TI  - Tips for successful outcomes for descending thoracic and thoracoabdominal aortic
      aneurysm procedures.
AB  - The continuing evolution of endovascular approaches to the repair of descending
      thoracic and thoracoabdominal aortic aneurysms necessitates careful evaluation of
      the safety and efficacy of these alternative therapies as they compare to the
      "gold standard" of open surgical repair. The purpose of this report is to present
      our approach to conventional open surgical repair of these aneurysms. Routine
      surgical modalities include use of moderate systemic heparinization, mild
      permissive hypothermia, and sequential aortic clamping. For extensive
      thoracoabdominal and select descending aortic procedures, additional modalities
      are used. The multimodal approach to organ protection during surgical treatment
      of descending thoracic and thoracoabdominal aneurysms has evolved substantially
      over the past 20 years. Experienced surgical centers now have much lower
      mortality and morbidity rates for these operations than previously reported.
      Current management strategies enable patients to undergo conventional open
      aneurysm repairs with excellent early survival and acceptable morbidity.

PMID- 18342731
TI  - Optimal exposure of thoracic inlet vascular structures: transmanubrial approach.
AB  - Exposure of the neurovascular structures of the thoracic inlet is limited by the
      bony thorax and clavicle. A cervicothoracic approach with resection of the medial
      one third of the clavicle or total claviculectomy provide excellent exposure but
      may render the patient with a significant cosmetic and functional defect. We
      describe a transmanubrial approach that preserves rigid fixation of the shoulder
      girdle and allows full access to the thoracic inlet. This technique is
      straightforward and may be easily modified to fit the particular needs of the
      patient, including access to the proximal brachiocephalic vessels, the hilum of
      the lung and the vertebral bodies of the lower cervical and upper thoracic spine.

PMID- 18342732
TI  - Technical tips for abdominal aortic endografting.
AB  - Favorable clinical results combined with increased patient demand for minimally
      invasive surgery has resulted in an increased application of endovascular aortic
      aneurysm repair (EVAR), and this treatment modality is now being extended to
      younger, healthier patients. While it seems that EVAR is becoming a desirable
      option for many patients, it is essential to realize that the feasibility of the
      procedure may be limited at times by patient anatomy and technical difficulties.
      Specific anatomical difficulties can be imposed by difficult access, short
      tortuous and calcified aortic and iliac landing zones, and presence of coincident
      complex iliac aneurysms. Renal failure has also presented a concern for patients
      being considered for treatment with EVAR, as the contrast loads required for the
      procedure, as well as for continued postoperative surveillance, may place the
      patient at risk. We will discuss technical maneuvers and considerations when
      encountering difficult anatomy and challenging surgical procedures.

PMID- 18342733
TI  - Technical tips for endovascular repair of common iliac artery aneurysms.
AB  - Isolated common iliac artery aneurysms are rare, comprising <2% of all aneurysm
      disease. These aneurysms present as either isolated disease, .03% of the
      population, or, in conjunction with abdominal aortic aneurysm, in approximately
      20% to 25% of such cases. Common iliac artery aneurysms are defined as any
      localized dilatation of the common iliac artery >1.5 cm in diameter. Elective
      repair for isolated common iliac artery aneurysms is generally not undertaken for
      aneurysms <3 cm in diameter unless they are part of an abdominal aortic aneurysm
      repair. Most common iliac artery aneurysms are found incidentally during
      abdominal/pelvic diagnostic imaging studies or at the time of pelvic or abdominal
      surgery. As with abdominal aortic aneurysms, endovascular repair of common iliac
      artery aneurysms follows techniques similar to those used for endovascular repair
      of abdominal aortic aneurysm. Management includes aneurysm exclusion with an
      endograft, which seals at sites within the proximal and distal common iliac
      artery and may involve coil occlusion of the hypogastric artery with extension of
      the reconstruction into the proximal external iliac artery, or use a "bell
      bottom" endograft limb placed at the common iliac bifurcation. Technical tips for
      successful outcome are described here, and all US Food and Drug Administration
      approved endografts have been used for repair. There were no statistically
      significant differences in outcomes that correlated with device or repair
      techniques used for management of common iliac artery aneurysms. Mid-term 54
      month outcome has been excellent, with no common iliac artery ruptures or
      aneurysm-related deaths and the need for secondary interventions was gratifyingly
      small.

PMID- 18342734
TI  - Femoral vein harvest for vascular reconstructions: pitfalls and tips for success.
AB  - The femoral-popliteal vein has proved to be an excellent conduit for a variety of
      indications. These include in situ reconstruction of infected aortic grafts, and
      mesenteric, brachiocephalic, and lower-extremity bypasses. This article discusses
      the technical details of successful deep vein harvest. Information regarding the
      preoperative evaluation, postoperative surveillance, reintervention, and venous
      morbidity is provided. The femoral-popliteal vein graft has proven to be a
      durable conduit with minimal late venous morbidity.

PMID- 18342735
TI  - Endovascular infrainguinal revascularization: technical tips for atherectomy
      device selection and procedural success.
AB  - The superficial femoral artery (SFA) is the interventionalist's most frequent
      adversary in infrainguinal revascularization, and we have yet to conquer it.
      Despite having numerous devices and techniques in our arsenal, we have, in large
      part, been unable to devise a treatment that yields not only excellent, safe, and
      reproducible acute outcomes, but also consistently good results at long-term
      follow-up. Angioplasty and stenting of the SFA has come under severe criticism
      due to numerous reports of stent fractures, unacceptable restenosis rates, and
      lack of US Food and Drug Administration-approved specific stents in this
      location. An alternative to displacement techniques is now being pursued. These
      include debulking the atheromatous plaque. We review these techniques and also
      offer helpful tips to achieve maximum success in infrainguinal revascularization.

PMID- 18342736
TI  - Endovenous and surgical extirpation of lower-extremity varicose veins.
AB  - Lower-extremity varicose veins are a very prevalent problem in the United States
      and represent a common referral for treatment. Therapeutic options for patients
      with lower-extremity superficial venous insufficiency have expanded in recent
      years, thanks to technological advances. Correction of both primary and secondary
      varicose veins can now be accomplished with endovenous and other minimally
      invasive techniques that allow for increased periprocedural patient comfort, as
      well as allowing more-rapid resumption of work or leisure activities with lower
      complication profiles. This article describes the first author's preferences and
      practice incorporating newer techniques for treatment of superficial venous
      reflux and varicose veins in an outpatient venous practice.

PMID- 18342737
TI  - Intravascular lead extraction using the excimer laser: pitfalls and tips for
      success.
AB  - Removal of retained pacemaker and defibrillator leads is often indicated in the
      face of infection, venous obstruction, or lead malfunction with the need to
      upgrade to a newer lead. While simple traction is often successful in newly
      placed or infected leads, chronic leads can be problematic in their removal. The
      laser extraction sheath offers a method for removal by "cutting" through scar
      tissue. This device can be potentially hazardous, so the laser lead extraction
      procedures should be performed in a properly equipped operating room for
      immediate cardiothoracic surgical intervention should massive bleeding occur.
      This article outlines a few suggestions for avoiding severe complications with
      this useful procedure.

PMID- 18342738
TI  - Brazilian intensive care nursing.

PMID- 18342740
TI  - Reprint of "Fiducial-less alignment of cryo-sections" [J. Struct. Biol. 159
      (2007) 413-423].
AB  - Cryo-electron tomography of vitreous sections is currently the most promising
      technique for visualizing arbitrary regions of eukaryotic cells or tissue at
      molecular resolution. Despite significant progress in the sample preparation
      techniques over the past few years, the three dimensional reconstruction using
      electron tomography is not as simple as in plunge frozen samples for various
      reasons, but mainly due to the effects of irradiation on the sections and the
      resulting poor alignment. Here, we present a new algorithm, which can provide a
      useful three-dimensional marker model after investigation of hundreds to
      thousands of observations calculated using local cross-correlation throughout the
      tilt series. The observations are chosen according to their coherence to a
      particular model and assigned to virtual markers. Through this type of
      measurement a merit figure can be calculated, precisely estimating the quality of
      the reconstruction. The merit figures of this alignment method are comparable to
      those obtained with plunge frozen samples using fiducial gold markers. An
      additional advantage of the algorithm is the implicit detection of areas in the
      sections that behave as rigid bodies and can thus be properly reconstructed.

PMID- 18342741
TI  - Reprint of "Stereology meets electron tomography: towards quantitative 3D
      electron microscopy" [J. Struct. Biol. 159 (2007) 443-450].
AB  - Stereological tools are the gold standard for accurate (i.e., unbiased) and
      precise quantification of any microscopic sample. The past decades have provided
      a broad spectrum of tools to estimate a variety of parameters such as volumes,
      surfaces, lengths, and numbers. Some of them require pairs of parallel sections
      that can be produced by either physical or optical sectioning, with optical
      sectioning being much more efficient when applicable. Unfortunately, transmission
      electron microscopy could not fully profit from these riches, mainly because of
      the large depth of field. Hence, optical sectioning was a long-time desire for
      electron microscopists. This desire was fulfilled with the development of
      electron tomography that yield stacks of slices from electron microscopic
      sections. Now, parallel optical slices of a previously unimagined small thickness
      (2-5nm axial resolution) can be produced. These optical slices minimize problems
      related to overprojection effects, and allow for direct stereological analysis,
      e.g., volume estimation with the Cavalieri principle and number estimation with
      the optical disector method. Here, we demonstrate that the symbiosis of
      stereology and electron tomography is an easy and efficient way for quantitative
      analysis at the electron microscopic level. We call this approach quantitative 3D
      electron microscopy.

PMID- 18342742
TI  - Reprint of "Three-dimensional elemental mapping of phosphorus by quantitative
      electron spectroscopic tomography (QuEST)" [J. Struct. Biol. 160 (2007) 35-48].
AB  - We describe the development of quantitative electron spectroscopic tomography
      (QuEST), which provides 3-D distributions of elements on a nanometer scale.
      Specifically, it is shown that QuEST can be applied to map the distribution of
      phosphorus in unstained sections of embedded cells. A series of 2-D elemental
      maps is derived from images recorded in the energy filtering transmission
      electron microscope for a range of specimen tilt angles. A quantitative 3-D
      elemental distribution is then reconstructed from the elemental tilt series. To
      obtain accurate quantitative elemental distributions it is necessary to correct
      for plural inelastic scattering at the phosphorus L(2,3) edge, which is achieved
      by acquiring unfiltered and zero-loss images at each tilt angle. The data are
      acquired automatically using a cross correlation technique to correct for
      specimen drift and focus change between successive tilt angles. An algorithm
      based on the simultaneous iterative reconstruction technique (SIRT) is
      implemented to obtain quantitative information about the number of phosphorus
      atoms associated with each voxel in the reconstructed volume. We assess the
      accuracy of QuEST by determining the phosphorus content of ribosomes in a
      eukaryotic cell, and then apply it to estimate the density of nucleic acid in
      chromatin of the cell's nucleus. From our experimental data, we estimate that the
      sensitivity for detecting phosphorus is 20 atoms in a 2.7 nm-sized voxel.

PMID- 18342743
TI  - Reprint of "On the feasibility of visualizing ultrasmall gold labels in
      biological specimens by STEM tomography" [J. Struct. Biol. 159 (2007) 507-522].
AB  - Labeling with heavy atom clusters attached to antibody fragments is an attractive
      technique for determining the 3D distribution of specific proteins in cells using
      electron tomography. However, the small size of the labels makes them very
      difficult to detect by conventional bright-field electron tomography. Here, we
      evaluate quantitative scanning transmission electron microscopy (STEM) at a beam
      voltage of 300kV for detecting 11-gold atom clusters (Undecagold) and 1.4nm
      diameter nanoparticles (Nanogold) for a variety of specimens and imaging
      conditions. STEM images as well as tomographic tilt series are simulated by means
      of the NIST Elastic-Scattering Cross-Section Database for gold clusters embedded
      in carbon. The simulations indicate that the visibility in 2D of Undecagold
      clusters in a homogeneous matrix is maximized for low inner collection semi
      angles of the STEM annular dark-field detector (15-20mrad). Furthermore, our
      calculations show that the visibility of Undecagold in 3D reconstructions is
      significantly higher than in 2D images for an inhomogeneous matrix corresponding
      to fluctuations in local density. The measurements demonstrate that it is
      possible to detect Nanogold particles in plastic sections of tissue freeze
      substituted in the presence of osmium. STEM tomography has the potential to
      localize specific proteins in permeabilized cells using antibody fragments tagged
      with small heavy atom clusters. Our quantitative analysis provides a framework
      for determining the detection limits and optimal experimental conditions for
      localizing these small clusters.

PMID- 18342744
TI  - Tricuspid regurgitation after cardiac transplantation: an old problem revisited.
AB  - Tricuspid regurgitation (TR) is the most common valvular abnormality after
      orthotopic heart transplantation (OHT), with a reported incidence of up to 84%,
      depending on the definition of significant regurgitation and surgical methods of
      OHT employed. While multiple etiologies are implicated in the development of TR
      after OHT, endomyocardial biopsy (EMB), performed to detect allograft rejection,
      is the single most important contributor to significant TR by causing anatomic
      disruption of the tricuspid valvular structure. Although the clinical course of
      TR is heterogeneous, hemodynamically significant regurgitation generally leads to
      progressive right-heart dysfunction and symptoms. In cases refractory to diuretic
      based medical therapy, surgical correction of TR has been shown to effectively
      alleviate the condition and provide symptomatic and organ function improvement.
      Tricuspid valve repair and replacement are viable surgical options, the
      application of which often depends on the institution's experience and underlying
      valve pathology. A non-invasive surveillance technique to detect allograft
      rejection is on the horizon, and may reduce the number of EMBs performed as well
      as the procedure-related tissue damage that leads to TR.

PMID- 18342745
TI  - Influence of inflow cannula length in axial-flow pumps on neurologic adverse
      event rate: results from a multi-center analysis.
AB  - BACKGROUND: The application of axial-flow pumps in patients with end-stage heart
      failure reveals a significantly reduced infectious complication rate as compared
      with rates observed with pulsatile devices. The remaining adverse event rate
      relates mainly to thromboembolic complications with neurologic consequences. We
      investigated the dependence of the neurologic adverse event rate on the length of
      the inflow cannula. METHODS: A total of 216 consecutive patients with an axial
      flow pump (INCOR; Berlin Heart GmbH, Berlin, Germany) were included in a
      retrospective multi-center analysis. In 138 patients, a short inflow cannula (24
      mm tip length into the left ventricle), and in 78 patients a long inflow cannula
      (tip length 34 mm) was applied. RESULTS: Patients with a long inflow cannula (LC)
      demonstrated a better survival rate than those with a short inflow cannula (SC)
      at the end of the observation period (LC, 63.4%; SC, 52.9%; p = 0.05). The
      thromboembolic adverse event rate was also significantly lower. Only 3 of the 78
      patients (3.8%) with an LC had a thromboembolic adverse event (thromboembolic
      events per patient-year = 0.11) as compared with 32 (23.2%) of SC patients
      (thromboembolic events per patient-year = 0.50, p < 0.001). CONCLUSIONS: Patients
      with a long inflow cannula had a better survival rate and a lower incidence of
      cerebrovascular adverse events than patients with a short inflow cannula.

PMID- 18342746
TI  - Effects of pulsatile- and continuous-flow left ventricular assist devices on left
      ventricular unloading.
AB  - BACKGROUND: In patients with end-stage heart failure, the use of left ventricular
      assist devices (LVADs) has improved clinical outcomes. Although newer continuous
      flow devices have significant advantages, the effect of continuous flow on left
      ventricular unloading and hemodynamics is less well established. The aim of this
      investigation was to compare the effects of pulsatile- vs continuous-flow LVADs
      on left ventricular reverse remodeling and hemodynamic indices. METHODS: Thirty
      five patients undergoing implantation with a pulsatile volume displacement pump
      operating at fixed speed (n = 15; HeartMate XVE; Thoratec Corp., Pleasanton, CA)
      or a continuous-flow rotary pump with an axial design operating at a fixed rotor
      speed (n = 20; HeartMate II; Thoratec) were evaluated. Right heart
      catheterization and echocardiography were performed pre-operatively, and at 1-
      and 6-month follow-up intervals. RESULTS: Thirty-five of 40 eligible patients
      with end-stage heart failure were included in this study. When used at fixed
      speed, use of both devices led to a substantial reduction in left ventricular
      volumes and dimensions at 1 month (p < 0.01). A marked and sustained reduction in
      filling pressures was also noted with both devices at 1 and 6 months (p < 0.01).
      The volume and pressure unloading effects of the HeartMate XVE were not superior
      to those with the HeartMate II (all p-values not statistically significant).
      CONCLUSIONS: Substantial left ventricular unloading and hemodynamic improvement
      is achieved with the HeartMate XVE and the HeartMate II. We conclude that
      continuous-flow LVADs are as effective as pulsatile-flow LVADs with regard to
      degree of left ventricular unloading and cardiac hemodynamics.

PMID- 18342747
TI  - Use of an intraperitoneal ventricular assist device with a
      polytetrafluoroethylene barrier decreases infections.
AB  - BACKGROUND: Infection rates for ventricular assist devices (VADs) are improving
      but the presence of infections remains problematic. Intraperitoneal pump
      placement may decrease the rate of infection. METHODS: This study is a single
      institution, retrospective comparison of infections for an extraperitoneal vs an
      intraperitoneal position with a polytetrafluoroethylene (PTFE) sheet separating
      the VAD from visceral organs. Implants were performed by a single surgical team
      from January 1, 2002 to May 31, 2006 (n = 65) for bridge-to-transplant or
      destination therapy. Patients with paracorporeal pumps (17 patients) or implant
      times of <30 days (n = 7; 4 died, 3 ongoing, 0 with pocket infections) were
      excluded. Thirty-five pulsatile left VADs were analyzed, whereas 6 rotary VADs
      were excluded from analysis. Twenty-three pulsatile VADs were placed in an
      extraperitoneal pocket (pocket patients) in 18 patients (5 patients had more than
      one left VAD implant), whereas 12 patients had intraperitoneal (IP patients) VAD
      placement. RESULTS: Infection with the implanted VAD occurred in 8 of 23 pocket
      implants (mean support 310 +/- 249 days) and 0 of 12 IP implants (mean support
      220 +/- 131 days; pocket vs IP infections: p = 0.003). Staphylococcus and
      Enterococcus accounted for most of the infections. Four infections in the pocket
      group recurred during VAD support. Two infected pocket patients had dehiscence of
      the mid-line wound. CONCLUSIONS: Infections of implanted VADs are associated with
      serious morbidity (e.g., prolonged antibiotic therapy, recurrent device
      infections and wound dehiscence). Placing VADs in an intraperitoneal position
      with a PTFE barrier to protect the viscera may reduce the prevalence of these
      infections.

PMID- 18342748
TI  - Graft side-mismatching for single-lung transplantation does not affect outcomes:
      role of the pre-operative quantitative lung perfusion scan.
AB  - BACKGROUND: There are concerns about which lung to explant during single-lung
      transplantation (SLT). Traditionally, a quantitative lung perfusion scan (QLPS)
      is performed, and the better-perfused lung is retained. Occasionally, there is
      transplantation with graft "side-mismatching," where the less-well-perfused lung
      is retained. We performed a retrospective study of patients undergoing SLT at our
      institution to evaluate the effects of side-mismatching (according to the QLPS)
      on graft performance and outcome. METHODS: We defined graft side-mismatching with
      a prospectively designed formula using baseline QLPS, and defined patients as
      either side-matched or side-mismatched. Data on mortality, requirement for
      cardiopulmonary bypass, relative graft perfusion, lung function and exercise
      capacity were obtained from institutional databases and patients' files. RESULTS:
      In a cohort of 114 patients, we defined 97 as having received a side-matched SLT
      and 17 as having received a side-mismatched graft. After lung transplantation,
      forced expiratory volume in 1 second (FEV(1)) and exercise capacity improved in
      both groups (p < 0.001). Patients with mismatched lungs had significantly higher
      relative graft perfusion post-operatively (p = 0.0012). There was no significant
      difference between the two groups (matched vs mismatched) in mortality,
      physiologic parameters and need for cardiopulmonary bypass. CONCLUSIONS: There is
      no apparent risk to the patient when a side-mismatched lung graft is
      transplanted. We conclude that side-mismatched lung transplantation appears to be
      feasible when required.

PMID- 18342749
TI  - Exudative bronchiolitis after lung transplantation.
AB  - BACKGROUND: After lung transplantation patients frequently develop small airways
      disease. Exudative bronchiolitis (EB) has not been described previously in this
      population. We describe a case series of patients who have developed EB after
      lung transplantation. METHODS: We reviewed the clinical records and radiologic
      data of 99 patients who underwent single and bilateral lung transplantation. Data
      relating to ethnicity, transplant indication, human leukocyte antigen (HLA)
      status, complications and survival were recorded. The EB cohort, defined by high
      resolution computed tomographic (HRCT) evidence of the disease, was compared with
      a group of patients who had not developed EB. RESULTS: The majority of patients
      had chronic obstructive pulmonary disease (COPD; n = 51), followed by cystic
      fibrosis (CF; n = 22), pulmonary fibrosis (n = 8), pulmonary hypertension (n =
      7), bronchiectasis (n = 5), lymphangioleiomyomatosis (n = 3) and Eisenmenger's
      syndrome (n = 3). Thirteen patients were found to have developed EB. EB was more
      commonly seen in Maori and Pacific Island patients (p < 0.05). EB was
      significantly associated with early infection post-transplant (p < 0.05) and a
      history of Aspergillus infection (p < 0.005) or diabetes (p < 0.05). The patients
      with EB were also significantly more likely to develop bronchiolitis obliterans
      syndrome (p < 0.0005), bronchiectasis (p < 0.0005) or small airways disease (p <
      0.05). Patients with EB had a varied response to treatment, with the majority
      showing improvement. CONCLUSIONS: EB was noted to occur after lung
      transplantation in a significant proportion of patients, but will not be detected
      unless HRCT is used routinely. It has been associated with patients' ethnicity,
      donor haplotype, infection and the development of airways disease. EB may be a
      prominent indicator of the likelihood of developing BOS.

PMID- 18342750
TI  - Outcome of influenza infection managed with oseltamivir in lung transplant
      recipients.
AB  - BACKGROUND: Influenza causes significant morbidity and mortality in lung
      transplant recipients and likely predisposes to obliterative bronchiolitis.
      Neuraminidase inhibitors shorten the duration of symptoms and virus shedding and
      the number of antibiotic-requiring complications in ambulatory immunocompetent
      patients, although the efficacy of these agents in lung transplant recipients has
      not been assessed previously. METHODS: In this study, 9 lung transplant patients
      who were treated with oseltamivir for influenza infections were identified and
      analyzed retrospectively. RESULTS: Oseltamivir was well tolerated. Infection
      resolved in all patients and there were no deaths. Two patients developed
      pneumonia shortly after their influenza infection and both responded to
      antibiotic therapy. None of the patients had persistent abnormalities noted on
      chest imaging and most did not show significant changes on pulmonary function
      testing. Two patients with the lowest pulmonary function test (PFT) values pre
      infection had persistent defects after infection. CONCLUSIONS: Oseltamivir is
      well tolerated in lung transplant recipients and may reduce the risk of
      complications, although further studies are warranted.

PMID- 18342751
TI  - Quilty indicates increased risk for microvasculopathy and poor survival after
      heart transplantation.
AB  - BACKGROUND: The impact of Quilty (sub-endocardial infiltration of lymphocytes) on
      the development of stenotic microvasculopathy and outcome after heart
      transplantation has not yet been evaluated. METHODS: Biopsies (n = 9,713)
      obtained within the first post-transplant year from 873 patients (722 men, age
      49.3 +/- 0.3 years) were evaluated by light microscopy (hematoxylin-eosin) for
      Quilty and cellular rejection (ISHLT), stenotic microvasculopathy (luminal
      radius:medial thickness ratio <1) and endothelial disease (core diameter:cell
      diameter ratio < or =1). Risk factors for stenotic microvasculopathy were
      analyzed by logistic regression. Overall survival and freedom from graft failure
      (cardiac re-transplantation, myocardial infarction and sudden cardiac death) were
      estimated by the Kaplan-Meier method and tested using a Cox proportional hazard
      model. RESULTS: We found 1,830 (19%) Quilty-positive biopsies in 481 (55%) Quilty
      formers and stenotic microvasculopathy in 866 (9%) biopsies of 379 (43%)
      patients. Evidence of Quilty (odds ratio [OR] 1.77; 95% confidence interval [CI]
      1.26 to 2.57) and endothelial disease (OR 4.98; 95% 95% CI 3.31 to 7.49)
      indicated higher risk, whereas post-transplant statin therapy was associated with
      lower risk for stenotic microvasculopathy (OR 0.68; 95% CI 0.48 to 0.97). Freedom
      from graft failure was lower in Quilty-formers (p = 0.0060) and even worse if
      patients suffered from both Quilty and stenotic microvasculopathy (p = 0.0017).
      Both factors were confirmed in multivariate regression analysis (stenotic
      microvasculopathy risk ratio [RR] 1.90, 95% CI 1.23 to 2.95; Quilty RR 1.77, 95%
      CI 1.11 to 2.82, p = 0.0430). CONCLUSIONS: Presence of Quilty indicates increased
      risk for stenotic microvasculopathy in biopsy early after heart transplantation.
      Both are associated with poor outcome due to graft failure.

PMID- 18342752
TI  - Clinical implications and longitudinal alteration of peripheral blood
      transcriptional signals indicative of future cardiac allograft rejection.
AB  - BACKGROUND: We have previously demonstrated that a peripheral blood
      transcriptional profile using 11 distinct genes predicts onset of cardiac
      allograft rejection weeks to months prior to the actual event. METHODS: In this
      analysis, we ascertained the performance of this transcriptional algorithm in a
      Bayesian representative population: 28 cardiac transplant recipients who
      progressed to moderate to severe rejection; 53 who progressed to mild rejection;
      and 46 who remained rejection-free. Furthermore, we characterized longitudinal
      alterations in the transcriptional gene expression profile before, during and
      after recovery from rejection. RESULTS: In this patient cohort, we found that a
      gene expression score (range 0 to 40) of <or =20 represents very low risk of
      rejection in the subsequent 12 weeks: 0 progressed to treatable (ISHLT Grade > or
      =3A) rejection; 16 of 53 (30%) from the intermediate group (those who progressed
      to ISHLT Grade 1B or 2) and 13 of 46 (28%) controls (who remained Grade 0 or 1A)
      had scores < or =20. A gene score of > or =30 was associated with progression to
      moderate to severe rejection in 58% of cases. These two extreme scores (< or =20
      or > or =30) represented 44% of the cardiac transplant population within 6 months
      post-transplant. In addition, longitudinal gene expression analysis demonstrated
      that baseline scores were significantly higher for those who went on to reject,
      remained high during an episode of rejection, and dropped post-treatment for
      rejection (p < 0.01). CONCLUSIONS: The use of gene expression profiling early
      after transplantation allows for separation into low-, intermediate- or high-risk
      categories for future rejection, permitting development of discrete surveillance
      strategies.

PMID- 18342753
TI  - Assessment and characterization of time-related differences in plaque composition
      by intravascular ultrasound-derived radiofrequency analysis in heart transplant
      recipients.
AB  - BACKGROUND: The survival of heart transplant patients is limited by cardiac
      allograft vasculopathy (CAV). Intravascular ultrasound (IVUS) and IVUS-derived
      radiofrequency plaque composition analysis (IVUS-RF) provide further information
      about the process of coronary atherosclerosis. METHODS: In this study we aimed to
      assess the time-dependent differences in disease progression in patients with
      CAV. Fifty-six patients were divided into three groups according to time interval
      after transplantation (Group I: 1 to 3 months, 18 patients; Group II, 1 to 5
      years, 20 patients; Group III: 5 to 15 years, 18 patients). RESULTS: IVUS-RF
      revealed time-dependent increases in all plaque components. The largest increase
      was shown for fibrotic, fibrofatty and necrotic tissue between Groups I and II.
      Dense calcium area increased uniformly in all groups. IVUS-RF-derived plaque type
      analysis revealed predominantly fibrotic plaques in all groups with a decrease of
      frequency over time. Fibrolipidic and fibrotic-calcific plaques increased
      uniformly. High-risk lesions, such as thick-cap fibroatheromas (FAs), increased
      in Groups I and II and decreased in Group III. Thin-cap FAs were detected only in
      Group III. CONCLUSIONS: IVUS-RF, as compared with gray-scale IVUS, provides
      better detailed information about the development of CAV by plaque morphology and
      composition analysis in different stages after heart transplantation. Serial IVUS
      RF analysis in these patients may improve the stratification of heart transplant
      recipients.

PMID- 18342754
TI  - Detection of high-grade stenoses with multislice computed tomography in heart
      transplant patients.
AB  - BACKGROUND: Post-transplant follow-up of heart transplant patients consists of
      repeated coronary angiography, which is associated with high costs, discomfort
      and risk. We sought to determine whether multislice computed tomography (MSCT)
      permits the exclusion or progression of coronary artery disease in heart
      transplant patients. METHODS: MSCT scanning (Philips CT MX 8000 IDT) and invasive
      coronary angiography were performed on 66 consecutive heart transplant patients.
      One hundred milliliters of non-ionic iodinated contrast medium was applied for CT
      angiography. For MSCT analysis, coronary arteries and side branches with a
      diameter > or =1.5 mm were assessed for the presence of luminal narrowing of
      >70%. MSCT results were compared with those of quantitative coronary angiography
      analysis. RESULTS: Ten patients (17%) had one significant stenosis, whereas 3
      patients (5%) had 2-vessel disease and none had 3-vessel disease. MSCT was
      performed successfully on 60 patients enrolled in our analysis. Forty-two of 44
      patients (95%) who were estimated to be fully evaluable for MSCT were correctly
      classified. On per-segment-based analysis, sensitivity, specificity and positive
      and negative predictive values were 59%, 94%, 91% and 99.43%, respectively. After
      exclusion of unevaluable segments, sensitivity and specificity increased to 71%
      and 99.86%, respectively. On per-patient-based analysis, sensitivity, specificity
      and positive and negative predictive values were 88%, 97%, 88% and 97%,
      respectively, in evaluable transplant recipients. CONCLUSIONS: MSCT with its high
      specificity and high negative predictive value allows the exclusion of
      significant coronary artery vasculopathy in evaluable patients. From the clinical
      point of view, this might spare additional invasive coronary angiography in heart
      transplant patients.

PMID- 18342755
TI  - Myocardial pro-inflammatory cytokine expression and cellular rejection in
      pediatric heart transplant recipients.
AB  - BACKGROUND: Accumulating evidence suggests that immune-mediated injury is
      important in the development of rejection after heart transplantation. We
      hypothesized that pro-inflammatory cytokine expression would increase in biopsy
      samples that manifest cellular rejection and that this would correlate with the
      development and progression of transplant cellular rejection. METHODS: Children
      with heart transplants were prospectively enrolled from July 2004 to November
      2005. Right ventricular endomyocardial biopsies were obtained during routine
      catheterization for rejection surveillance. Cellular rejection was graded using
      criteria established by the International Society for Heart and Lung
      Transplantation. RNA was extracted from biopsy samples and reverse transcription
      was used for complementary DNA synthesis. The cDNA product was evaluated by
      quantitative real-time polymerase chain reaction (PCR) to measure the following
      cytokines: interleukin (IL)-1beta, IL-6 and IL-18; tumor necrosis factor-alpha
      (TNF-alpha); and interferon-gamma (IFN-gamma). Normalized cytokine mRNA
      transcripts were correlated with cellular rejection scores and the presence of
      viral genome. RESULTS: Seventy-four children (mean age 9.6 +/- 5.5 years, range
      0.2 to 20.5 years) were enrolled and 95 biopsies were obtained. None of the
      cytokines demonstrated a correlation with the cellular rejection score, even
      within individual patients for whom multiple, serial biopsy samples were studied.
      Eighteen biopsy samples were found to have parvovirus B19 genome present, but
      there was no correlation between cytokine levels and the presence of parvovirus.
      CONCLUSIONS: Cytokine transcripts in heart transplants do not correlate with
      cellular rejection. In addition, there is no correlation between cytokine
      transcripts and the presence of viral genome.

PMID- 18342756
TI  - Performance of limited sampling strategies for predicting mycophenolic acid area
      under the curve in thoracic transplant recipients.
AB  - BACKGROUND AND METHODS: Eight limited sampling strategies (LSSs) for estimating
      mycophenolic acid area under the concentration-time curve (4 developed from lung
      transplant recipients at our center, 4 developed for heart transplant recipients
      from other research groups) were evaluated in 27 heart or heart-kidney transplant
      patients. RESULTS: The LSSs from our lung transplant patients performed well when
      applied to the heart transplant population, with percent bias and percent
      precision within the acceptable limit of +/-15%. CONCLUSIONS: The LSSs developed
      at our center are robust enough to be applied to both lung and heart transplant
      populations. Application of LSSs from other research groups yielded less optimal
      results, reinforcing the need to re-establish or re-validate LSSs for each
      specific center.

PMID- 18342757
TI  - Pulmonary hypertension in end-stage pulmonary sarcoidosis: therapeutic effect of
      sildenafil?
AB  - BACKGROUND: The objectives of this study were to assess the frequency and
      severity of pulmonary hypertension (PH) and the effect of sildenafil treatment in
      patients with recalcitrant pulmonary sarcoidosis. METHODS: This investigation was
      a single-center, retrospective study of all patients (n = 25) with end-stage
      pulmonary sarcoidosis referred for lung transplantation. Hemodynamic measurements
      were evaluated by right-side cardiac catheterization in 24 of 25 patients.
      Sildenafil treatment for patients with sarcoidosis-associated PH was introduced
      in April 2004. RESULTS: The study group of 24 patients (16 men, 8 women) had a
      median age of 45 (range 35 to 58) years, and duration of sarcoidosis of 11 (range
      2 to 38) years. Mean pulmonary arterial pressure (MPAP) was median 36 (range 18
      to 73) mm Hg. PH (MPAP >25 mm Hg) was present in 19 of 24 patients (79%).
      Sildenafil was administered to 12 of 13 patients at a dose of 150 (range 75 to
      225) mg/day for 4 (range 1 to 12) months. Sildenafil treatment was associated
      with reductions in MPAP of -8 mm Hg (CI -1 to -15 mm Hg), and PVR -4.9 Wood units
      (CI -7.2 to -2.6 Wood units). Cardiac output and cardiac index also increased
      during treatment (p = 0.01, respectively). There were no consistent changes in 6
      minute walk distance. CONCLUSIONS: Patients with severe pulmonary sarcoidosis
      have a high prevalence of PH. Sildenafil treatment was associated with
      significant improvements in hemodynamic parameters.

PMID- 18342758
TI  - Prevalence and characteristics of restless legs syndrome in patients with
      pulmonary hypertension.
AB  - BACKGROUND: Patients with pulmonary hypertension (PH) have an increased
      prevalence of risk factors for restless legs syndrome (RLS). We performed a cross
      sectional study to determine the prevalence and characteristics of RLS in this
      population. METHODS: Patients filled out two questionnaires during a visit: (1) a
      diagnostic tool for RLS, based on the core clinical features; and (2) a 10
      question rating scale used to assess severity. Data were obtained by medical
      record review with regard to demographics, characteristics of PH and known RLS
      risk factors. RESULTS: Restless legs syndrome was found in 43.6% (24 of 55) (mean
      age +/- SD: 49 +/- 14 years; 41 women, 14 men) of patients and 54% of these had
      moderate or severe RLS. Patients with RLS were younger but gender differences
      were not appreciated. Presence of RLS did not correlate with measures of PH
      severity; however, patients with RLS were more likely to have a better 6-minute
      walk distance (p = 0.015) and lower BNP level (p = 0.07) and less likely to be
      WHO Class IV or require oxygen during the 6-minute walk test. Patients with a
      history of hypothyroidism (67%; p = 0.04) and those on opioids for relief of leg
      pain (69%) were more likely to have RLS. CONCLUSIONS: Patients with PH had a very
      high prevalence of RLS and most had moderate or severe symptoms. RLS was more
      common in more active patients and those who were hypothyroid or on opioids for
      relief of leg pain. Patients with PH should be screened for RLS because good
      treatment options are available.

PMID- 18342759
TI  - Prognostic value of timing and duration characteristics of exercise oscillatory
      ventilation in patients with heart failure.
AB  - BACKGROUND: Exercise oscillatory ventilation (EOV) occurs in a sub-group of
      patients with increased heart failure (HF) severity and poorer prognosis. The
      purpose of this investigation was to examine the prognostic value of the largest
      ventilatory oscillation characteristics in HF patients. METHODS: One hundred
      fifty-four subjects diagnosed with HF underwent cardiopulmonary exercise testing.
      Subjects with EOV were then divided into two sub-groups: (1) largest ventilatory
      oscillation during the first half of exercise with an oscillation width > or =30
      seconds; and (2) largest ventilatory oscillation during the second half of
      exercise or an oscillation width <30 seconds. Subjects were tracked for major
      cardiac events after the exercise test. RESULTS: The fifty-five subjects (35.7%)
      in the overall group demonstrating EOV during the exercise test were at
      significantly higher risk for adverse events (hazard ratio = 3.0, 95% confidence
      interval 1.6 to 5.5, p < 0.001). The prognostic value of this ventilatory
      phenomenon improved when only subjects with the largest ventilatory oscillation
      during the first half of exercise with an oscillation width > or =30 seconds were
      defined as having EOV (hazard ratio = 3.6, 95% confidence interval 1.6 to 7.9, p
      = 0.002). CONCLUSIONS: In this study we found that the characteristics of the
      largest oscillatory ventilation provide valuable prognostic information in
      patients with EOV.

PMID- 18342760
TI  - Use of extracorporeal membrane oxygenation as a bridge to primary lung
      transplant: 3 consecutive, successful cases and a review of the literature.
AB  - Many transplant centers have considered extracorporeal membrane oxygenation
      (ECMO) to be a contraindication to lung transplantation, due to historically poor
      outcomes. However, recent advances in the technical aspects of ECMO have enabled
      patients to be supported with relative safety for several weeks until a donor
      lung becomes available. We present 3 young patients with acute (in 1 case, acute
      on chronic), severe respiratory failure that was refractory to conventional
      ventilation, who were placed on venovenous ECMO. In each case, a clinical
      decision was made that the patient's respiratory failure was irreversible and
      they were successfully managed with urgent lung transplantation.

PMID- 18342761
TI  - Successful radiofrequency ablation therapy for intractable ventricular
      tachycardia with a ventricular assist device.
AB  - Refractory ventricular tachycardia (VT) can be a potentially life-threatening
      rhythm in the presence of non-ischemic dilated cardiomyopathy, particularly when
      it results in hemodynamic compromise. A 65-year-old man with non-ischemic
      cardiomyopathy was referred for multiple episodes of VT. A HeartMate left
      ventricular assist device (LVAD) was implanted to stabilize and control the VT.
      However, he had multiple episodes of VT and the frequency of ventricular
      arrhythmias did not improve after LVAD implantation. He required electrical
      cardioversion to treat each episode. On Day 41 post-operatively, radiofrequency
      ablation was performed. Two significant areas of scarring were identified and
      were successfully ablated. After ablation, he did not have significant sustained
      VT episodes and was discharged.

PMID- 18342762
TI  - Current topics in radiology health services research.

PMID- 18342763
TI  - Digital mammography: are there advantages in screening for breast cancer?
AB  - Digital mammography separates the processes of image acquisition, processing, and
      display, which allows for the optimization of each process. The result addresses
      some of the limitations of screen film mammography. This work reviews the
      advantages of the decoupling of the processes and the clinical trials comparing
      digital mammography with film-screen mammography in the screening setting.
      Advanced applications of digital mammography, such as contrast-enhanced digital
      mammography and tomosynthesis, are also discussed.

PMID- 18342764
TI  - Breast MRI for cancer detection and characterization: a review of evidence-based
      clinical applications.
AB  - RATIONALE AND OBJECTIVES: Breast MRI is an important new tool in the imaging
      armamentarium for the detection and characterization of breast carcinoma.
      Understanding the evidence-supported benefits and potential harms of breast MRI
      is important to ensure the appropriate utilization of this medical resource.
      MATERIALS AND METHODS: This article reviews the clinical settings in which MRI
      for breast cancer assessment has been shown to be advantageous. The evidence
      regarding the diagnostic accuracy of MRI and the impact of this imaging tool on
      clinical outcomes are described. Novel breast MRI techniques which may lead to
      future improvements in performance are discussed. RESULTS: Breast MRI has been
      shown in multiple studies to be advantageous for screening patients at high risk,
      evaluating patients with a new breast cancer diagnosis, monitoring treatment
      response in patients undergoing neoadjuvant chemotherapy and evaluating patients
      with metastatic axillary adenocarcinoma and unknown primary site. Among the
      limitations of MRI are its high cost and modest specificity resulting in false
      positive examinations. CONCLUSIONS: When used in evidence-supported clinical
      settings, the high sensitivity of MRI results in earlier cancer detection or
      greater accuracy of detection compared to existing tests for breast carcinoma.
      Further scientific endeavors are crucial to optimize the future performance and
      application of breast MRI.

PMID- 18342765
TI  - Communication in the diagnostic mammography suite: implications for practice and
      training.
AB  - RATIONALE AND OBJECTIVES: The diagnostic mammography suite is a microcosm of
      challenging physician-patient communication in radiology. Little has been written
      about communication practices in the diagnostic mammography suite, the effect of
      this communication on both physicians and patients, and implications for
      radiology training programs. We surveyed radiology residents and staff about
      communication training, practices, and experiences communicating directly with
      patients in the diagnostic mammography suite. MATERIALS AND METHODS: We asked the
      membership of the Association of Program Directors in Radiology to disseminate
      surveys to radiology residents and staff radiologists in their institutions. We
      analyzed response frequencies and correlations. RESULTS: We received responses
      from 142 residents and 120 staff radiologists. More than half of staff
      respondents spoke personally with every patient who had an abnormal diagnostic
      mammogram; 37% felt they had inadequate time to do so. Most residents and staff
      highly rated their own communication skills and confidence in ability to explain
      results and respond to patients' emotions, but experienced stress doing so. A
      majority of respondents reported no formal communication skills education after
      medical school. Twenty-nine percent of staff respondents regularly observed
      residents' communication with patients and 39% of residents reported receiving
      feedback about their communication. Residents' opportunities to observe staff
      communicate with a patient and to receive feedback on their own patient
      interactions were correlated with self-rated communication skill and confidence
      in ability to respond to patients' emotions (P < .05). CONCLUSIONS: Radiologists
      engage in challenging and stressful patient communication interactions. There is
      a paucity of educational curricula on interpersonal and communication skills in
      radiology. This has implications for both patient and physician satisfaction and
      patient outcomes.

PMID- 18342766
TI  - Patients as partners in radiology education: an innovative approach to teaching
      and assessing patient-centered communication.
AB  - RATIONALE AND OBJECTIVES: Effective communication is essential for high quality
      care, yet little is known about radiologists' communication with patients, what
      constitutes "best communication practices," and how best to teach and evaluate
      it. We piloted educational strategies and an assessment instrument to teach and
      evaluate radiologists' communication skills. We focused on communication in the
      diagnostic mammography suite, where patient-radiologist interactions are often
      intense and stressful. MATERIALS AND METHODS: We adapted existing instruments to
      create a Radiology Communication Skills Assessment Tool (RCSAT). We piloted an
      educational program that included patients as teachers and raters of
      interpersonal and communication skills, and implemented a radiology objective
      structured clinical examination (OSCE). We measured radiology residents' self
      assessed skills, confidence and stress, as well as patient-rated communication
      skills using the RCSAT. RESULTS: Residents' baseline self-assessed communication
      skills regarding abnormal mammograms were fair, confidence in their communication
      was minimal, and they found this communication stressful. Overall baseline
      communication skills, rated by patient-teachers using the RCSAT, were 3.62 on a 5
      point scale (1 = poor to 5 = excellent). Analysis of post-OSCE debriefing
      comments yielded nine themes regarding effective radiology communication, as well
      as residents' reflections on the communication challenges they experience. The
      themes were integrated into subsequent RCSAT revisions. Residents' reflections
      were used to inform teaching workshops. CONCLUSION: Educational curricula on
      communication about difficult information can be implemented in radiology
      training programs. Radiology residents' performance can be assessed using a
      communication skills assessment tool during standardized patient-teacher
      encounters. Further research is necessary in this important domain.

PMID- 18342767
TI  - Is e-mail communication effective in changing ordering patterns in the emergency
      department? A case study of computed tomography for pulmonary embolus.
AB  - RATIONALE AND OBJECTIVES: We sought to evaluate the effectiveness of e-mail
      communication to reduce the utilization of computed tomography for pulmonary
      thromboembolism (PE) in young patients (aged 40 and under) in our institution.
      MATERIALS AND METHODS: An e-mail was sent to all of our institution's emergency
      department (ED) physicians in response to a series of negative PE studies in
      young females. The periods 90 days before and 90 days after were evaluated to
      assess the total number of PE studies performed in patients aged 40 and younger,
      the rate of positivity, and the utilization of D-dimer and ventilation/perfusion
      scans during each period. RESULTS: Over the 180-day period, a total of 65 PE
      studies were ordered in patients aged 40 and younger in the ED. Studies were
      positive for PE in 1 of 33 (3%) before the e-mail and 4 of 32 (12.5%) after (P =
      .343). There was no difference in the number of D-dimer studies ordered during
      each period for patients studied with computed tomography. Ventilation/perfusion
      scanning was not performed on any ED patients younger than 40 during the 180-day
      period. CONCLUSIONS: One-time e-mail communication was not effective in changing
      ED ordering habits of PE studies. Scant information exists in regard to effective
      clinician-to-clinician communication. Further evaluation for successful
      mechanisms to promote health practice reform and quality improvement is
      necessary.

PMID- 18342768
TI  - Emergency MRI utilization trends at a tertiary care academic medical center:
      baseline data.
AB  - RATIONALE AND OBJECTIVES: This study evaluates utilization trends of emergency
      department (ED)-ordered magnetic resonance imaging (MRI) examinations in an adult
      academic medical center over a 5-year period (2001-2005). MATERIALS AND METHODS:
      MRI examinations from the ED-ordering location were identified by searching the
      radiology information system (RIS). Overall MRI volume and ED patient encounters
      were also assessed during the same period. Each examination was assessed by type
      of examination, examination completion time, and primary and secondary clinical
      indications by reviewing the RIS and medical record. RESULTS: During the study
      period, 1,900 ED-ordered MRI examinations were performed on 1,020 patients.
      During the same period, 62,823 total MRI examinations were performed, and the
      total ED patient volume was 420,840. ED-ordered MRI volume increased 391% over
      the study period (125 to 614 examinations/year), whereas total MRI volume
      increased only 38.9% and ED patient volume in our institution actually decreased
      by -9%. MRI examinations of the brain, magnetic resonance angiography of the head
      and neck, and spinal MRI were the most commonly ordered tests. Clinical
      indications were analyzed. Peak times of ED-ordered examination completion were
      between 4:00 PM and 11:00 PM. A total of 15.5% of examinations required overtime
      or callback of MRI technologists for completion. CONCLUSIONS: Multiple reasons
      are suggested that may increase utilization (perceived need for diagnostic
      certainty, as well as medico-legal and patient-driven factors). Whether this
      increase in MRI utilization resulted in improved patient outcomes is unclear and
      should be studied further. Implications for radiologist coverage and resident
      training are discussed.

PMID- 18342769
TI  - Diagnostic performance of positron emission tomography in the detection of
      coronary artery disease: a meta-analysis.
AB  - RATIONALE AND OBJECTIVES: Although myocardial perfusion positron emission
      tomography (PET), using either cyclotron-produced ammonia or generator-produced
      rubidium 82, has reported excellent diagnostic capabilities in the detection of
      coronary artery disease (CAD) in individual studies, the technique is not widely
      used in practice. This may be driven by cost and availability or by unawareness
      of performance. The purpose of our study was to conduct an evidence-based
      evaluation of PET in the diagnosis of CAD. MATERIALS AND METHODS: We examined
      studies from January 1977 to July 2007 using MEDLINE and EMBASE. A study was
      included if it (1) used PET as a diagnostic test for CAD and (2) used catheter x
      ray angiography as the reference standard (> or =50% diameter stenosis). Analysis
      was performed on a subject and coronary territory level. RESULTS: Nineteen
      studies (1442 patients) met the inclusion criteria. On a patient level, PET
      demonstrated a sensitivity of 0.92 (95% confidence interval [CI]: 0.90-0.94) and
      specificity of 0.85 (CI: 0.79-0.90), with a positive likelihood ratio (LR+) of
      6.2 (CI: 3.3-11.8) and negative likelihood ratio (LR-) of 0.11 (CI: 0.08-0.14).
      On a coronary territory level (n = 1130), PET showed a sensitivity of 0.81 (CI:
      0.77-0.84) and specificity of 0.87 (CI: 0.84-0.90), with an LR+ of 5.9 (CI: 4.5
      7.9) and an LR- of 0.19 (CI: 0.09-0.38). CONCLUSION: PET demonstrates excellent
      diagnostic properties in the diagnosis of CAD, especially at the patient level.
      The capabilities appear superior to those reported in meta-analyses for perfusion
      imaging with Tl-201 and sestamibi, or anatomical imaging with coronary MDCT
      angiography or MRA. Given that previous studies have found PET to be cost
      effective and the current findings of excellent sensitivity and specificity, the
      modality should be more widely considered as an initial test in the diagnosis of
      CAD.

PMID- 18342770
TI  - Comparison of diagnostic accuracy of 64-slice computed tomography coronary
      angiography in patients with low, intermediate, and high cardiovascular risk.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to compare the diagnostic
      accuracy of 64-slice computed tomographic coronary angiography (CTCA) in groups
      of patients with low, intermediate, and high risk for coronary artery disease
      (CAD) events. MATERIALS AND METHODS: The institutional review board approved this
      study; written informed consent was obtained from all patients. Eighty-eight
      consecutive patients with suspected CAD (40 women; mean age, 64.3 +/- 9.4 years;
      range, 39-82) underwent CTCA, calcium scoring, and invasive coronary angiography
      and were grouped according to their Framingham 10-year risk for hard coronary
      events into low (<10%), intermediate (10%-20%), and high (>20%) risk categories.
      Significant stenoses (luminal diameter narrowing > or =50%) were assessed on an
      intention-to-diagnose-basis; no coronary segment was excluded and nonevaluative
      segments were rated false positive. To determine differences between groups,
      Kruskal-Wallis tests were performed for individually determined values of
      diagnostic performance. RESULTS: Per-patient sensitivity, specificity, negative
      predictive, and positive predictive values were 90.0%, 79.2%, 95.0%, and 64.3%,
      respectively, with low (n = 34), 87.5%, 92.3%, 85.7%, and 93.3%, respectively,
      with intermediate (n = 29), and 100%, 75.0%, 100%, and 89.5%, respectively, with
      high risk (n = 25), with a trend toward higher positive predictive value (P =
      .07). Per-segment negative predictive value was lower with high pretest
      probability (P < .01). Mean calcium-score units were 90, 220, and 312 (P = .23),
      and the prevalence of CAD was 29.4%, 55.2%, and 68.0% (P < .01) with low,
      intermediate, and high risk. CONCLUSION: Sensitivity and specificity of CTCA are
      not influenced by the prevalence of CAD, whereas the negative predictive value is
      lower and the positive predictive value tends to be higher in patients with a
      high prevalence of CAD.

PMID- 18342771
TI  - Screening for familial intracranial aneurysms: decision and cost-effectiveness
      analysis.
AB  - RATIONALE AND OBJECTIVES: To evaluate the potential benefits, harms, and cost
      effectiveness of screening for asymptomatic, unruptured intracranial aneurysms in
      family members of patients with aneurysmal subarachnoid hemorrhage (SAH).
      MATERIALS AND METHODS: Using a Markov model, we performed a decision and cost
      effectiveness analysis comparing magnetic resonance (MR) angiography screening
      for asymptomatic, unruptured intracranial aneurysms to no screening in family
      members of patients with aneurysmal SAH. Treatment of unruptured intracranial
      aneurysms was determined according to patient age and aneurysm size and location.
      Cohort age was taken as 40 years. RESULTS: In family members with two or more
      affected first-degree relatives, screening compared with no screening had an
      incremental cost-effectiveness ratio (ICER) of $37,400 per quality-adjusted life
      year (QALY). With screening, life expectancy increased from 39.44 years to 39.55
      years. The ICER of screening was >$50,000 per QALY if age at screening was > or
      =50 years. In family members with one affected first-degree relative, screening
      compared with no screening had an ICER of $56,500 per QALY. CONCLUSIONS: The
      results suggest that MR angiography screening for asymptomatic, unruptured
      intracranial aneurysms in family members with two or more affected first-degree
      relatives is cost-effective. The benefit and cost-effectiveness are dependent on
      age at screening.

PMID- 18342772
TI  - The impact of acoustic noise found within clinical departments on radiology
      performance.
AB  - RATIONALE AND OBJECTIVES: In recent years, there has been increasing interest in
      the impact of environmental factors such as ambient light on radiologist
      performance. One commonly encountered distractor found within all clinical
      departments that has received little or no attention is acoustic noise. MATERIALS
      AND METHODS: The present work records the level of noises encountered within
      environments where radiologic images are viewed and establishes the impact of a
      clinically relevant level of noise on the ability of radiologists to perform a
      typical diagnostic task. Noise levels were recorded 10 times within each of 14
      environments, 11 of which were locations where radiologic images are judged.
      Thirty chest images were then presented to 26 senior radiologists, who were asked
      to detect up to three nodular lesions within 30 posteroanterior chest x-ray
      images in the absence and presence of noise at an amplitude demonstrated in the
      clinical environment. Jackknife free-response receiver-operating characteristic
      analyses was performed on the free-response data. RESULTS: The results
      demonstrated that noise amplitudes rarely exceeded that encountered with normal
      conversation with the maximum mean value for an image-viewing environment being
      56.1 dB. This level of noise had no impact on the ability of radiologists to
      identify chest lesions with figure of merits of 0.68, 0.69, and 0.68 with noise
      and 0.65, 0.68, and 0.67 without noise for chest radiologists, nonchest
      radiologists, and all radiologists, respectively. Equally, no differences were
      seen for false-positive and false-negative scores or on the time required to
      judge the images. CONCLUSION: These findings suggest that noise at levels
      encountered within areas where radiologic images are viewed is not a major
      distractor within the reporting environment, but the need for further work has
      been identified.

PMID- 18342773
TI  - MDCT of the myocardium: a new contribution to ischemic heart disease.
AB  - RATIONALE AND OBJECTIVES: Despite the progress made in diagnosis and treatment,
      cardiovascular diseases remain the main cause of death worldwide. MATERIALS AND
      METHODS: Multidetector row computed tomography (MDCT) provides several diagnostic
      insights, namely assessment of coronary artery anatomy and measurement of left
      ventricular volume and function. The ability of CT to show myocardial infarcted
      areas as an enhanced territory was described in the late 1970s in an animal
      model. RESULTS: This method found a second wind with the arrival of MDCT
      technology that led to its clinical application. Several authors describe the
      ability of MDCT to assess myocardial injury both in animals and humans. The MDCT
      assessment of myocardial late enhancement is based on the same principle as
      delayed enhancement MRI. CONCLUSIONS: The aim of this review is to cover the
      technical aspects of cardiac MDCT in assessing the myocardium and its potential
      in diagnosing ischemic heart disease.

PMID- 18342774
TI  - Optimization of region of interest luminances may enhance radiologists' light
      adaptation.
AB  - RATIONALE AND OBJECTIVES: Radiologic image details are best discriminated at
      luminance levels to which the eye is adapted. Recommendations that ambient light
      conditions are matched to overall monitor luminance to encourage appropriate
      adaptation are based on an assumption that clinically significant regions within
      the image match average monitor luminance. The current work examines this
      assumption. MATERIALS AND METHODS: Three image types were considered:
      posteroanterior (PA) chest; PA wrist; and computed tomography (CT) head.
      Luminance at clinically significant regions was measured at hilar region and
      peripheral lung (chest), distal radius (wrist), and supraventricular white matter
      (head). Average monitor luminances were calculated from measurements at 16
      regions of the display face plate. Three ambient light levels-30, 100 and 400 lux
      were employed. Thirty samples of each image type were used. RESULTS:
      Statistically significant differences were noted between average monitor
      luminances and clinically important regions of interest of up to a factor of 3.8,
      2, and 6.3 for chest, wrist, and CT head images respectively (P < .0001). Values
      for the hilum of the chest and distal radius were higher than average monitor
      levels, whereas the reverse was observed for the peripheral lung and CT brain.
      Increasing ambient light had no impact on results. CONCLUSIONS: Clinically
      important radiologic information for common radiologic examinations is not being
      presented to observers in a way that facilitates optimized adaptation. This may
      have a significant impact on the ability of the observer to identify details with
      low contrast discriminability. The importance of image-processing algorithms
      focussing on clinically significant abnormalities rather than anatomic regions is
      highlighted.

PMID- 18342775
TI  - The disruptive professional case scenarios.
AB  - This article examines certain critical aspects relating to the clinical
      competency of professionalism. A discussion is presented which is centered on an
      analysis of two fictional scenarios explored from the standpoint of a current and
      a former program director, an associate dean, a department chair, and a lawyer.
      These cases are followed by a series of questions and a legal discussion which
      can then be used for either individual study or group discussion.

PMID- 18342778
TI  - Murine models of chronic graft-versus-host disease: insights and unresolved
      issues.
AB  - Chronic graft-versus-host-disease (cGVHD) is a major barrier to successful
      allogeneic hematopoietic stem cell transplantation (allo-HSCT), with highly
      variable clinical presentations. The pathophysiology of cGVHD remains relatively
      poorly understood. The utilization of murine models to study cGVHD encompasses
      experimental challenges distinct from those that have been successfully used to
      study acute GVHD (aGVHD). Nevertheless, despite these challenges, murine models
      of cGVHD have contributed to the understanding of cGVHD, and highlight its
      mechanistic complexity. In this article, insights into the pathophysiology of
      cGVHD obtained from murine studies are summarized in the context of their
      relevancy to clinical cGVHD. Despite experimental limitations, current and future
      models of murine cGVHD will continue to provide insights into the understanding
      of clinical cGVHD and provide information for new therapeutic interventions.

PMID- 18342779
TI  - Chronic Graft-versus-Host Disease--implementation of the National Institutes of
      Health Consensus Criteria for Clinical Trials.

PMID- 18342780
TI  - A role for TNF receptor type II in leukocyte infiltration into the lung during
      experimental idiopathic pneumonia syndrome.
AB  - Idiopathic pneumonia syndrome (IPS) is a frequently fatal complication following
      allogeneic stem cell transplantation (allo-SCT). Experimental models have
      revealed that TNF-alpha contributes to pulmonary vascular endothelial cell (EC)
      apoptosis, and modulates the infiltration of donor leukocytes into the lung
      parenchyma. The inflammatory effects of TNF-alpha are mediated by signaling
      through the type I (TNFRI) or type II (TNFRII) TNF receptors. We investigated the
      relative contribution of TNFRI and TNFRII to leukocyte infiltration into the lung
      following allo-SCT by using established murine models. Wild-type (wt) B6 mice or
      B6 animals deficient in either TNFRI or TNFRII were lethally irradiated and
      received SCT from allogeneic (LP/J) or syngeneic (B6) donors. At week 5 following
      SCT, the severity of IPS was significantly reduced in TNFRII-/- recipients
      compared to wt controls, but no effect was observed in TNFRI-/- animals.
      Bronchoalveolar lavage fluid (BALF) levels of RANTES and pulmonary ICAM-1
      expression in TNFRII-/- recipients were also reduced, and correlated with a
      reduction of CD8(+) cells in the lung. Pulmonary inflammation was also decreased
      in TNFRII-/- mice using an isolated MHC class I disparate model (bm1 --> B6), and
      in bm1 wt mice transplanted with B6 TNF-alpha-/- donor cells. Collectively, these
      data demonstrate a role for TNF-alpha signaling through TNFRII in leukocyte
      infiltration into the lung following allo-SCT, and suggest that disruption of the
      TNF-alpha:TNFRII pathway may be an effective tool to prevent or treat IPS.

PMID- 18342781
TI  - Potential role of a mismatched HLA-specific CTL clone developed pre-transplant in
      graft rejection following cord blood transplantation.
AB  - Graft rejection is a serious complication in cord blood transplantation (CBT),
      but little is known about the mechanism of rejection. To investigate the
      potential role of T lymphocytes in graft rejection, we isolated a CD8(+)
      cytotoxic T lymphocyte (CTL) clone of recipient origin from blood obtained from a
      patient with graft rejection after CBT from an HLA-mismatched unrelated donor.
      The isolated CTL clone specifically recognized an HLA-B( *)1501 molecule as an
      alloantigen, which was expressed in donor cells but not in recipient cells. The
      results of a microchimerism analysis specific for HLA-B( *)1501 and a polymerase
      chain reaction assay specific for the T cell receptor on DNA from pretransplant
      peripheral blood mononuclear cells revealed that the patient was exposed to HLA
      B( *)1501 prior to CBT, and that the CTL clone was in the patient's blood prior
      to transplantation. The present study demonstrates a potential role for
      pretransplant CTL in graft rejection following CBT.

PMID- 18342782
TI  - Chronic kidney disease after nonmyeloablative stem cell transplantation in
      adults.
AB  - Chronic kidney disease (CKD) after myeloablative stem cell transplantation (SCT)
      is a well-established problem. Little is known about CKD after nonmyeloablative
      SCT. We performed a retrospective cohort study of 108 adults who received
      nonmyeloablative SCT with fludarabine and/or total-body irradiation (TBT)
      conditioning. Renal function was assessed by estimating glomerular filtration
      rate (GFR) with the MDRD equation. CKD was defined as GFR <60 mL/min/1.73 m(2).
      CKD developed in 15% of patients after a median of 15 months. None of the
      patients required dialysis. Cumulative incidence of CKD was 7% at 12 months, 14%
      at 24 months, and 22% at 48 months. Risk factors for CKD were female sex (P =
      .021), older age (P = .040), and lower GFR pretransplant (P < .001).
      Complications after SCT were not associated with CKD. SCT nephropathy, a cause of
      CKD after myeloablative SCT, did not occur. Overall survival (OS) was 66%. There
      was no difference in survival between patients with or without CKD. In
      conclusion, CKD is a frequent complication after nonmyeloablative SCT and is not
      related to SCT nephropathy. Women, patients above 50 years of age, and patients
      with slightly decreased kidney function pretransplant have the greatest risk of
      development of CKD.

PMID- 18342783
TI  - ABO incompatibility is associated with increased non-relapse and GVHD related
      mortality in patients with malignancies treated with a reduced intensity regimen:
      a single center experience of 221 patients.
AB  - The effect of ABO-incompatibility on transplantation outcome remains a
      controversial issue, with many of the reported studies showing conflicting
      results. In this study, we evaluate: the association between ABO-incompatibility
      and myeloid engraftment; the incidence and severity of acute and chronic graft
      versus-host disease (GVHD); non-relapse mortality (NRM); GVHD-associated
      mortality, relapse and overall survival (OS). Our study includes 221 patients
      with malignant diseases treated in the same institution with the same reduced
      intensity regimen. Other variables known to affect the transplantation outcome
      such as age, disease, disease risk, and donor characteristics were well-balanced
      between ABO-matched and ABO-mismatched transplants. Analysis of our data shows
      increased incidence of NRM during the first months after transplantation in the
      groups of patients with major and minor ABO-incompatibility. Although neither
      incidence nor severity of GVHD differed significantly among the different groups,
      we found increased mortality associated with GVHD in the major ABO-incompatible
      groups. Long-term OS and relapse rate were not different, although we observed a
      trend for decreased OS during the first year post transplantation in the group of
      patients with major ABO-incompatibility. Our study showed that ABO
      incompatibility has an adverse impact on the transplantation outcome.

PMID- 18342784
TI  - Allogeneic transplantation with reduced-intensity conditioning for Hodgkin and
      non-Hodgkin lymphoma: importance of histology for outcome.
AB  - Allogeneic stem cell transplantation (SCT) with reduced-intensity conditioning
      (RIC) has the potential to lead to long-term remissions for patients with
      lymphoma. However, the role of RIC SCT in the treatment of lymphoma is still
      unclear. Specifically, the relative benefit of RIC SCT across lymphoma
      histologies and the prognostic factors in this population are incompletely
      defined. We retrospectively analyzed the outcomes of 87 patients with advanced
      lymphoma who underwent RIC SCT at the Dana-Farber Cancer Institute over a 6-year
      period with a homogeneous conditioning regimen consisting of fludarabine and low
      dose busulfan. Thirty-six patients had Hodgkin disease (HD) and 51 had non
      Hodgkin lymphoma (NHL). Sixty-eight percent had undergone prior autologous
      transplantation. The 1-year cumulative incidence of nonrelapse mortality was 13%,
      and the 3-year cumulative incidence of progression was 49%. The incidence of
      grade 3-4 acute GVHD was 11%. The 2-year cumulative incidence of chronic GVHD was
      68%, and its development was associated with a decreased risk of progression and
      an improved progression-free survival (PFS). Three-year overall survival (OS) was
      56% for patients with HD, 81% for indolent NHL, 42% for aggressive NHL, and 40%
      for mantle cell lymphoma. The corresponding figures for 3-year PFS were 22%, 59%,
      22%, and 30%, respectively. Multivariate analysis identified elevated
      pretransplantation lactate dehydrogenase (LDH) as an adverse factor for PFS,
      while indolent NHL histology was favorable. For OS, advanced age and elevated
      pretransplantation LDH were adverse factors, whereas indolent NHL histology was
      favorable. Low early donor chimerism was not predictive of poor outcome in
      univariate or multivariate analyses. Moreover, progression was not associated
      with loss of chimerism. These results emphasize the importance of lymphoma
      histology for patients undergoing RIC SCT, as well as the lack of relevance of
      donor chimerism for outcome in this patient population.

PMID- 18342785
TI  - Circulating endothelial progenitor cells decreased in patients with
      sclerodermatous chronic graft-versus-host disease.
AB  - Chronic graft-versus-host disease (cGVHD) is a common late complication of
      allogeneic stem cell transplantation (allo-SCT). Some cGVHD patients develop skin
      lesions, and the skin lesions in sclerodermatous cGVHD (s-cGVHD) patients
      resemble those in progressive systemic sclerosis (PSS), which is characterized by
      impaired production of circulating endothelial progenitor cells (EPCs). We
      investigated, retrospectively, whether low EPC production may promote the
      development of sclerodermatous lesions in cGVHD. Peripheral blood (PB) was
      obtained from 14 healthy volunteers and 27 allo-SCT patients. Five patients
      developed s-cGVHD. CD34(+) cells were purified by using the magnetic cell-sorting
      separation system, and the CD34(+)/CD133(+)/vascular endothelial growth factor
      (VEGF) receptor-2(+) EPCs were quantified. The endothelial cell colony-formation
      potential was evaluated. Serum VEGF and basic fibroblast growth factor (b-FGF)
      concentrations were measured by ELISA. The s-cGVHD patients had significantly
      lower median circulating EPCs frequencies than non-s-cGVHD patients or control
      (145 of 20 mL [interquartial range-IQR 107-193] versus 1083.5 [IQR 669.3-2151]; P
      = .0023, and versus 1530.5 [IQR 961.3-2158]; P = .0012, respectively). They also
      had impaired median endothelial-forming ability compared to non-s-cGVHD patients
      or controls (3.8 [IQR 1.0-4.3] versus 12.8 [IQR 8.8-28.8], and versus 26.4 [IQR
      23.6-30.6], respectively; P = .0012). Their VEGF and b-FGF serum levels were also
      higher than in controls. In conclusion, s-cGVHD patients show findings consistent
      with those seen in PSS with impaired vasculogenesis that may limit blood
      perfusion and may contribute to the development of sclerodermatous lesions.

PMID- 18342786
TI  - Incidence, predisposing factors, and outcome of engraftment syndrome in pediatric
      allogeneic stem cell transplant recipients.
AB  - Engraftment syndrome (ES) has been recognized as an inflammatory condition during
      neutrophil recovery after hematopoietic stem cell transplantation (HSCT)
      characterized by noninfectious fever and skin rash. It has been reported to occur
      frequently after autologous HSCT in children and adults, and has been shown to be
      an independent risk factor for increased transplant-related mortality (TRM).
      However, virtually no data exist on its occurrence after allogeneic HSCT in
      children. To determine incidence, predisposing factors for, and complications of
      ES in a pediatric transplant cohort, we analyzed 61 consecutive recipients of a
      myeloablative allogeneic HSCT for the occurrence of ES. Diagnosis of ES was
      established when children presented with > or =2 of the following symptoms within
      7 days before engraftment: (1) fever >38.0 degrees C, (2) skin rash, (3) weight
      gain and albumin drop, or (4) dyspnea, hypoxia, and pulmonary infiltrates.
      Incidence of ES in this cohort was 48% (29 of 61). In a univariate analysis,
      posttransplant granulocyte-colony stimulating factor (G-CSF) administration (P =
      .02), and high mononuclear cell count (MNC) (P = .002) were identified as
      significant risk factors predisposing for the development of ES. In a multiple
      logistic regression analysis, amphotericin B therapy (P = .009) and high MNC (P =
      .004) were significant explanatory variables for ES risk. There was a slight
      trend toward a higher rate of chronic GVHD (cGVHD) in patients with ES (P = .11).
      However, after a median follow-up of 9.5 years overall survival (OS) (P = .53)
      and TRM (P = .65) did not differ between the 2 groups. ES presenting with fever,
      rash, weight gain, and pulmonary symptoms should be recognized as a frequent
      complication of allogeneic HSCT after myeloablative conditioning in children.
      Treatment with G-CSF, amphotericin B, and a high nucleated cell count of the
      graft predisposed for the development of ES in this study. OS and TRM in this
      cohort were not affected by the occurrence of ES.

PMID- 18342787
TI  - Second stem cell transplantation in patients with Fanconi anemia using
      antithymocyte globulin alone for conditioning.
AB  - Despite the promising data on the outcome of allogeneic stem cell transplantation
      (SCT) in patients with Fanconi anemia (FA), a certain percentage of these
      patients still experience graft failure; some of these patients undergo second
      transplants, but the existing data on the outcome of the second SCT in FA
      patients are scarce, with no long-term follow-up provided in many of the
      publications addressing this issue. This is a review of our experience in 4 such
      patients who underwent second stem cell transplants using rabbit ATG only for
      conditioning. Three engrafted promptly and are alive and free of disease at 25,
      23, and 21 months, respectively. We conclude, therefore, that the use of ATG
      alone for conditioning before a second SCT may offer a chance of long-term
      disease-free survival for FA patients who fail their first transplant.

PMID- 18342788
TI  - Impact of graft cell dose on transplant outcomes following unrelated donor
      allogeneic peripheral blood stem cell transplantation: higher CD34+ cell doses
      are associated with decreased relapse rates.
AB  - Peripheral blood stem cells (PBSC) have been increasingly used in the matched
      unrelated donor (MUD) transplant setting, but the impact of CD34(+) cell dose on
      outcomes in this setting have not been well characterized. We analyzed 181
      consecutive patients who underwent MUD-PBSC transplantation at the City of Hope
      between August 2000 to December 2004. Patients were conditioned with either full
      intensity regimen or reduced-intensity regimen. There was a significant inverse
      relationship between higher CD34(+) cell dose and faster neutrophil engraftment
      (r = -0.16, P = .035). By univariate analysis, a CD34(+) cell dose > or =4.2 x
      10(6)/kg (above the lowest quartile) was associated with significantly lower
      relapse risk (hazard ratio [HR] = 0.67, P = .0126), with a trend for
      corresponding improvement for disease-free survival (HR = 0.84, P = .12) but not
      overall survival (HR = 0.91, P = .46). The impact of the CD34(+) cell dose
      remained significant in multivariate analysis. The higher CD34(+) cell dose was
      significantly associated with faster recovery of absolute lymphocyte counts on
      day +30 posttransplant. Subset analysis demonstrated that the higher CD34(+) cell
      dose was associated with (1) greater reduction in relapse in myeloid malignancies
      than that in lymphoid malignancies, (2) greater reduction in reduced-intensity
      conditioning than in full-intensity conditioning, (3) greater reduction in
      relapse when there is a inhibitory killer-cell immunoglobulin-like receptor
      ligand (iKIRL)-mismatch in the gravft-versus-host (GVH) direction, and (4)
      greater reduction in relapse when there is a lack of iKIRL, suggesting that the
      protective effect of CD34(+) cell dose against relapse may be immune-mediated,
      possibly through NK cell recovery.

PMID- 18342789
TI  - Transplantation in remission improves the disease-free survival of patients with
      advanced myelodysplastic syndromes treated with myeloablative T cell-depleted
      stem cell transplants from HLA-identical siblings.
AB  - From 1985 to 2004, 49 patients with advanced myelodysplastic syndromes (MDS) (>
      or =5% blasts) or acute myeloid leukemia (AML) transformed from MDS underwent T
      cell depleted bone marrow or peripheral blood hematopoietic stem cell
      transplantation (HSCT) from HLA-identical siblings following conditioning with a
      myeloablative regimen that included total body irradiation (44 patients) or
      busulfan (5 patients). Thirty-six patients received chemotherapy (3 low dose and
      33 induction doses) before conditioning, and 13 patients did not receive any
      chemotherapy. Prior to transplantation, 22 of the 36 treated patients were in
      hematologic remission; 4 were in a second refractory cytopenia phase (26
      responders); 8 had failed to achieve remission; and 2 of the responders had
      progression or relapse of their MDS (10 failures). No post-transplantation
      pharmacologic prophylaxis for graft-versus-host disease (GVHD) was given. The
      median age was 48 yrs (range 13-61). Forty-five of the 49 patients engrafted; 2
      had primary graft failure; and 2 died before engraftment. Only 3 patients
      developed acute GVHD (aGVHD) (grades I and III) and 1 chronic GVHD (cGVHD). At 3
      yrs post-transplantation, the overall survival (OS) was 54% in the responders;
      31% in the untreated group; and 0% in the failure group (P=.0004). The disease
      free survival (DFS) was 50%, 15% and 0% in each group respectively (P=.0008). In
      multivariate analysis, disease status before cytoreduction remained highly
      correlated with DFS (P<.001). The cumulative incidence (CI) of relapse at 2-yrs
      post-transplantation for the responders was 23%; for the untreated group was 38%;
      and for the failures was 50%. The CI of non-relapse mortality at 2-yrs post
      transplantation, for the responders was 23%; for the untreated group was 38%; and
      for the failures was 40%. All survivors achieved a Karnofsky Performance Status
      (KPS) of > or =90. These results indicate that patients with advanced MDS who
      achieve and remain in remission or a second refractory cytopenia phase with
      chemotherapy before conditioning can achieve successful long-term remissions
      following a myeloablative T cell depleted allogeneic HSCT.

PMID- 18342790
TI  - Haploidentical hematopoietic stem cell transplantation without in vitro T cell
      depletion for treatment of hematological malignancies in children.
AB  - To investigate the efficacy and safety of haploidentical (from family member
      donors) hematopoietic stem cell transplantation (HSCT) for children. 42 children
      under 14 yrs old with hematological malignancies underwent haploidentical HSCT.
      Outcomes were analyzed. Thirty-three children were classified as high-risk
      candidates. Of 42 patient/donor pairs, 4 (9.5%) were mismatched in 2 HLA loci, 15
      (35.7%) in 3 loci, and 23 (54.8%) in 4 loci. Follow-ups were performed for a
      median of 1110 (449-1959) days after transplantation. All patients achieved
      stable engraftments. The cumulative incidence of acute graft-versus-host disease
      (aGVHD) of grade 2-4 was 57.2%, and that of grade 3-4 was 13.8%. The cumulative
      incidence of chronic graft-versus-host disease (cGVHD) was 56.7% for total and
      29.5% for extensive. Twenty-seven patients survived with a 3-yr probability of
      leukemia-free survival (LFS), 57.3+/-8%, 18 of them were in the high-risk group.
      Fifteen patients died, 4 from infection, 7 from relapse of leukemia, 2 from heart
      failure, one from severe aGVHD, and one from lymphoproliferative disorders. The
      results encourage extending haploidentical HSCT without T cell depletion
      treatments to children with an indication for transplantation.

PMID- 18342791
TI  - Evidence of a graft-versus-Hodgkin lymphoma effect in the setting of extensive
      bone marrow involvement.

PMID- 18342792
TI  - Allogeneic hematopoietic stem cell transplantation for peripheral T cell
      lymphomas; evidence of graft-versus-T cell lymphoma effect.

PMID- 18342793
TI  - Genetics--getting personal.

PMID- 18342794
TI  - Australia--the premier Asia-Pacific hub for biotech investment.

PMID- 18342795
TI  - Polymorph control: past, present and future.
AB  - The appearance and disappearance of polymorphs is no longer a mysterious and
      inexplicable process. Although methods for polymorph control are still imperfect,
      there is a large armoury of methods that can be used to tackle this important and
      challenging problem. We survey the methods and their successes over the last few
      years.

PMID- 18342796
TI  - From a glucocentric to a lipocentric approach towards metabolic syndrome.
AB  - Insulin resistance, the essential component of metabolic syndrome, has
      traditionally been defined from a glucocentric viewpoint, with glucotoxicity
      playing a lead role. However, as overabundant circulating fatty acids are now
      known to be overt contributors, there is a paradigm shift in the understanding of
      metabolic syndrome acknowledging the importance of lipotoxicity as a major
      perpetuator of insulin resistance. Ectopic accumulation of fat in liver, adipose,
      muscle and pancreatic islets, provokes insulin resistance through various
      mechanisms. Chronic inflammation/adipocytokine generation, endoplasmic reticulum
      stress and mitochondrial dysfunction/oxidative stress also contribute
      significantly towards insulin resistance. Targets that can act as counter
      regulators/master switches at the converging point of all these metabolic
      pathways are currently under intense development.

PMID- 18342797
TI  - Towards improving compound selection in structure-based virtual screening.
AB  - Structure-based virtual screening is now an established technology for supporting
      hit finding and lead optimisation in drug discovery. Recent validation studies
      have highlighted the poor performance of currently used scoring functions in
      estimating binding affinity and hence in ranking large datasets of docked
      ligands. Progress in the analysis of large datasets can be made through the use
      of appropriate data mining techniques and the derivation of a broader range of
      descriptors relevant to receptor-ligand binding. In addition, simple scoring
      functions can be supplemented by simulation-based scoring protocols. Developments
      in workflow design allow the automation of repetitive tasks, and also encourage
      the routine use of simulation-based methods and the rapid prototyping of novel
      modelling and analysis procedures.

PMID- 18342798
TI  - Helping science to succeed: improving processes in R&D.
AB  - Bringing drugs to the market remains a costly and, until now, often unpredictable
      challenge. Although understanding the underlying science is key to further
      progress, our imperfect knowledge of disease and complex biological systems
      leaves excellence in execution as the most tangible lever to sustain our
      serendipitous approach to drug discovery. The problems encountered in
      pharmaceutical R&D are not unique, but to learn from other industries it is
      important to recognise similarity, rather than differences, and to advance
      industrialisation of R&D beyond technology and automation. Tools like Lean and
      Six Sigma, already applied to increase business excellence across diverse
      organisations, can equally be introduced to pharmaceutical R&D and offer the
      potential to transform operations without large-scale investment.

PMID- 18342799
TI  - Motilin, ghrelin and related neuropeptides as targets for the treatment of GI
      diseases.
AB  - Motilin and ghrelin are released from the upper gut during fasting, to stimulate
      gastric motility. Additional actions of ghrelin (e.g. changes in appetite, nausea
      or endocrine functions) improve the possibility of using ghrelin receptor
      agonists to treat complex disorders such as functional dyspepsia. However,
      changes in endocrine functions increase the risk of unacceptable side effects. By
      comparison, the more restricted prokinetic activity of motilin limits the
      therapeutic possibilities but improves the risk:benefit ratio. Compounds
      targeting both receptors are in development. Recently, additional peptides have
      been identified from preproghrelin (obestatin) and prepromotilin. These exert
      biological activity but their pathophysiological significance is unknown.

PMID- 18342800
TI  - Translational dermatology in drug discovery: perspectives for integrating
      humanized xenograft models and experimental clinical studies.
AB  - Application of humanized xenotransplantation disease models and experimental
      clinical studies in the context of translational research in drug discovery in
      dermatology is an opportunity to reduce failure due to lack of efficacy in
      clinical development stage.

PMID- 18342801
TI  - Drug delivery from the oral cavity: focus on a novel mechatronic delivery device.
AB  - Dental drug delivery systems have been used for a long time, in particular for
      the local therapy of diseases affecting the oral cavity. Research today
      concentrates on the design of formulations to increase their retention time. Even
      today, however, prosthetic devices incorporating drug delivery are rarely used.
      Mainly, they are focused on prophylaxis and the release of antibacterial agents.
      However, as buccal delivery, because of its undeniable advantages, has become
      popular for systemic drug delivery, and prolonged well-controlled release has
      been identified as beneficial, especially for chronic diseases, a new class of
      delivery systems is evolving: highly miniaturized computerized delivery systems,
      integrated into a dental appliance. Dental delivery systems today are used in two
      ways: the main application is the local treatment of diseases affecting the oral
      cavity itself like periodontitis or fungal infections. The second is for systemic
      drug delivery.

PMID- 18342802
TI  - New insights into the causes and therapy of cerebral vasospasm following
      subarachnoid hemorrhage.
AB  - Cerebral vasospasm lingers as the leading preventable cause of death and
      disability in patients who experience aneurysmal subarachnoid hemorrhage. Despite
      the potentially devastating consequences of cerebral vasospasm, the mechanisms
      behind it are incompletely understood. Nitric oxide, endothelin-1, bilirubin
      oxidation products and inflammation appear to figure prominently in its
      pathogenesis. Therapies directed at many of these mechanisms are currently under
      investigation and hold significant promise for an ultimate solution to this
      substantial problem.

PMID- 18342803
TI  - Discovery of tight junction modulators: significance for drug development and
      delivery.
AB  - Tight junction biology has many important applications, from improving knowledge
      of diseases characterized by the loss of epithelial or endothelial tissue barrier
      function to providing a mechanistic basis for improving non-invasive drug
      delivery. A variety of chemical and molecular biological tools have been
      developed, including high throughput cell-based screening of molecular libraries
      that facilitate discovery of novel peptides and lipids to modulate tight junction
      function safely and reversibly. Further development of novel tight junction
      modulating excipients necessitates consideration of physicochemical,
      toxicological, pharmaceutical and regulatory issues.

PMID- 18342804
TI  - Advances in measuring cellular bioenergetics using extracellular flux.
AB  - Cell-based assays have become a favored format for drug discovery because living
      cells have relevant biological complexity and can be highly multiplexed to screen
      for drugs and their mechanisms. In response to a changing extracellular
      environment, disease and/or drug exposure, cells remodel bioenergetic pathways in
      a matter of minutes to drive phenotypic changes associated with these
      perturbations. By measuring the extracellular flux (XF), that is the changes in
      oxygen and proton concentrations in the media surrounding cells, one can
      simultaneously determine their relative state of aerobic and glycolytic
      metabolism, respectively. In addition, XF is time-resolved and non-invasive,
      making it an attractive format for studying drug effects in vitro.

PMID- 18342806
TI  - Why is clinical progress in acute myelogenous leukemia so slow?

PMID- 18342807
TI  - Apoptosis in leukemia: from molecular pathways to targeted therapies.
AB  - Knowledge about apoptosis pathways developed in the last few years is already
      being translated into novel targeted therapies. Two illustrative approaches to
      this process are the development of small molecule BCL2 inhibitors and X-linked
      inhibitors of apoptosis proteins (XIAP) inhibitors. This work demonstrates both
      the development of new agents based on molecular mechanisms and how these agents
      further our understanding of the biology of apoptosis.

PMID- 18342808
TI  - Can FLT3 inhibitors overcome resistance in AML?
AB  - The identification of FLT3 mutations across a range of the cytogenetic subgroups
      of AML has opened up the possibility of a targeted therapeutic approach with
      broad applicability. Four agents are currently in clinical trials, at least 3 of
      which have both sufficient activity against AML and sufficiently acceptable
      toxicity profiles to support continued efforts to refine their inclusion into
      therapeutic regimens for AML. Better understanding of the genetics of inherent
      and acquired resistance is needed to guide development of second-generation
      agents. Optimizing the integration of FLT3 inhibitor therapy with chemotherapy
      has the potential both to decrease toxicity and improve response.

PMID- 18342809
TI  - Has gene expression profiling improved diagnosis, classification, and outcome
      prediction in AML?
AB  - Gene expression profiling, the simultaneous measurement of the global patterns of
      gene expression in cells using microarray technologies, has held promise to
      improve diagnosis, risk classification, and outcome prediction in acute leukemias
      as well as in other human cancers. But how much has gene expression profiling
      impacted or improved current diagnosis and risk classification schemes and
      therapeutic targeting in acute myeloid leukemia (AML)? To date, gene expression
      profiling of AML has largely confirmed the presence of well-established recurring
      cytogenetic abnormalities, such as translocations, deletions, point mutations, or
      normal karyotypes, and has led to the identification of sets of genes reflective
      of these abnormalities. The use of expression profiling and statistical modeling
      to develop molecular classifiers that improve outcome prediction beyond
      traditional prognostic variables or the targeting of patients to specific
      therapies or transplantation has been less successful. Similarly, expression
      profiling has not led to the identification of many novel therapeutic targets in
      AML. Using advanced statistical modeling techniques, our group has focused on
      expression profiling in adult AML patients with poor risk features in order to
      identify novel cluster groups and potential targets for therapy in this highly
      resistant form of disease. To further advance the application of gene expression
      profiling and other comprehensive genomic and phosphoproteomic techniques to the
      study of AML, it would be ideal for the NCI Cooperative Groups to register all
      patients to common or intergroup collaborative clinical trials or registration
      studies in order to develop large, well-characterized cohorts of uniformly
      treated patients for future research studies.

PMID- 18342810
TI  - New approaches in acute myeloid leukemia.
AB  - Today, treatment of patients with acute myeloid leukemia (AML) remains
      predominantly a "one-fits-all" approach with intensive cytarabine-based
      chemotherapy as the mainstay, but we are finally beginning to reap the rewards of
      decades of basic, translational, and clinical research. Developing
      individualized, "targeted" therapy for each AML patient based on unique molecular
      features of disease remains a daunting goal, yet one that we can now begin to
      envision. Hypothesis-based study designs--from preclinical/laboratory experiments
      to phase 1 and subsequent efficacy trials--provide the foundation for advances in
      the diagnosis, risk stratification, and treatment of patients with AML. The
      following is an outline of several key areas of ongoing AML research.

PMID- 18342812
TI  - Consolidation therapy: what should be the standard of care?
AB  - Adults 18-60 years old with acute myelogenous leukemia (AML) should undergo some
      form of postremission therapy, however, how much and what kinds of postremission
      chemotherapy remain unclear. In contrast, for older patients more than one cycle
      of chemotherapy postremission does not appear justified except perhaps in those
      rare patients with favorable cytogenetics who are young enough to tolerate
      standard therapy and in whom there is still an option for cure. Routine
      postremission therapy is not justifiable for those with unfavorable cytogenetics.
      However, the median age of AML patients approaches 70 years; this is a group of
      patients who often reach minimal disease, but with a median disease-free survival
      of only 4 to 5 months, regardless of their cytogenetics, and are therefore an
      ideal patient group for clinical studies. Older patients have limited tolerance
      for intensive regimens, although relatively nontoxic agents exist that can be
      explored. The issue of maintenance remains open.

PMID- 18342811
TI  - Is it important to decipher the heterogeneity of "normal karyotype AML"?
AB  - Almost half of adult acute myelogenous leukemia (AML) is normal cytogenetically,
      and this subgroup shows a remarkable heterogeneity of genetic mutations at the
      molecular level and an intermediate response to therapy. The finding of recurrent
      cytogenetic abnormalities has influenced, in a primary way, the understanding and
      treatment of leukemias. Yet "normal karyotype AML" lacks such obvious
      abnormalities, but has a variety of prognostically important genetic
      abnormalities. Thus, the presence of a FLT3-ITD (internal tandem duplication),
      MLL-PTD (partial tandem duplication), or the increased expression of ERG or EVI1
      mRNAs confer a poor prognosis, and an increased risk of relapse. In contrast, the
      presence of cytoplasmic nucleophosmin or C/EBPA mutations is associated with
      lower relapse rates and improved survival. Although resistance to treatment is
      associated with specific mutations, the degree to which the leukemia resembles a
      stem cell in its functional properties may provide greater protection from the
      effects of treatment. Although usually all of the circulating leukemia cells are
      cleared following treatment, a small residual population of leukemic cells in the
      bone marrow persists, making this disease hard to eradicate. Increased
      understanding of the biological consequences of at least some of these mutations
      in "normal karyotype AML" is leading to more targeted approaches to develop more
      effective treatments for this disease.

PMID- 18342813
TI  - Older adults: should the paradigm shift from standard therapy?
AB  - For older adults (ie, those age 60 and above) with acute myelogenous leukemia,
      patient and clinician have three choices: standard therapy, ie, a "3+7" regimen
      or low-dose ara-C, investigational therapy, or palliative care. Investigational
      treatments sponsored by pharmaceutical companies tend to exclude the 10-20% of
      older patients who have a poor performance status (Zubrod >2), an increased
      bilirubin, or creatinine (>1.9 mg/ml) and who are thereby unlikely to do well
      with standard therapy. However, even excluding such patients, standard treatment
      offers little obvious benefit for most older patients. Nonetheless, these older
      patients are not uniform and can be stratified to receive investigational
      therapy, which is mandatory for most, or standard therapy, which is not
      inappropriate for some.

PMID- 18342814
TI  - Hematopoietic cell transplantation for patients with myelodysplastic syndromes
      (MDS): when, how and for whom?
AB  - Hematopoietic cell transplantation (HCT) offers potentially curative therapy for
      patients with myelodysplastic syndromes (MDS). However, who should and can be
      transplanted, with which approach, and when is a matter of debate. Various
      classification schemes and prognostic scoring systems have helped in the decision
      making process. Offering HCT to patients who were not considered transplant
      candidates in the past is now possible with the development of new transplant
      strategies. In addition to disease stage, patient age, comorbid conditions,
      preHCT chemotherapy, type of donor, source of stem cells, and possibly other
      factors, need to be considered prior to transplant. Patients without substantial
      comorbid conditions up to 60 years with the availability of unrelated donor
      grafts or 65 years with related donor grafts can be transplanted with more
      conventional (higher dose) regimens (e.g. targeted BU/CY; Flu/BU). Older patients
      and patients with comorbid conditions should be enrolled in trials aimed at
      optimizing RIC/nonmyeloablative HCT (e.g. Flu/melphalan; Flu/low dose TBI).
      Patients who present with 'advanced' MDS or are transfusion dependent, and do not
      have a del(5q), should probably be transplanted early in their course. GVHD (in
      all patients) and post-HCT relapse (in patients with high risk disease) remain
      major problems. Modifications of transplant conditioning regimens have reduced
      transplant-related mortality and allow successful HCT even in older patients.
      However, prospective randomized trials are needed to determine the role of pre
      HCT chemotherapy and the type of transplant conditioning regimen best suited for
      a given patient.

PMID- 18342815
TI  - Should all unrelated donors for transplantation be matched?
AB  - Previous analyses have suggested that hematopoietic cell transplantation (HCT)
      from an unrelated donor results in better survival if the patient is younger and,
      possibly also if the donor is younger. Additionally, survival is improved if HCT
      is performed during early disease stage and if the recipient and possibly the
      donor are cytomegalovirus (CMV) seronegative. Equivocal data have been published
      comparing bone marrow vs. (granulocyte-colony stimulating factor) G-CSF
      stimulated peripheral blood stem cells for transplantation. A randomized trial is
      underway by the Blood and Marrow Transplant Clinical Trials Network that is
      testing the prospective comparison of bone marrow vs. primed peripheral blood
      grafts from unrelated donors and patients with hematologic malignancies. Of most
      significance, however, is that the best donor is HLA-compatible, healthy,
      promptly available, and willing to give the requested product for HCT.

PMID- 18342816
TI  - Incorporating hematopoietic cell transplantation (HCT) into the management of
      adults aged under 60 years with acute myeloid leukemia (AML).
AB  - Current strategies for incorporating hematopoietic cell transplantation into the
      treatment of adults with AML are based predominantly on pre-treatment patient,
      donor and disease characteristics. These strategies, while useful, have
      significant shortcomings in that they recommend deferred transplantation for many
      patients who would benefit from earlier intervention and, at the same time,
      direct other patients who would be cured with chemotherapy alone to the more
      risky and toxic approach of early transplantation. Here we review the currently
      accepted indications for transplantation and raise the possibility that
      alternative approaches to incorporating transplantation into the management of
      adults with AML that rely predominantly on the measurement of minimal residual
      disease (MRD) could save additional lives without any major advance in
      chemotherapy or transplant technologies.

PMID- 18342817
TI  - Are there effective new strategies for the treatment of acute and chronic GvHD?
AB  - The molecular biology and pathophysiology underlying graft-versus-host disease
      (GvHD) remains an area of intensive research. Understanding normal and abnormal
      developments of both the innate and adaptive immune systems are beginning to
      provide understanding of the details of relevant pathways. Recent work in gene
      expression profiling suggests a critical next step in identifying broader
      patterns that will stand up to examination in independent data sets and provide a
      sturdy basis for targeted therapy and preventive measures against GvHD.

PMID- 18342818
TI  - The uses and benefits of cluster analysis in pharmacy research.
AB  - PURPOSE: Cluster analysis (CA) refers to a set of analytic procedures that reduce
      complex multivariate data into smaller subsets or groups. Compared with other
      data reduction methods, such as factor analysis, CA yields groupings that are
      based on the similarity of whole cases, as opposed to the individual variables
      that comprise those cases. CA represents a valuable analytic tool for the health
      sciences, and may be used to devise patient or consumer profiles, or in the
      development of classification systems or taxonomies. CA has become a more widely
      used analytic tool because before the advent of personal computers with high
      processing power, CA methods were too complex to be time efficient. Yet in the
      past few decades, interest in and the applied use of CA have advanced
      considerably. CA tools are now integrated into most popular statistical software
      packages and are therefore more accessible. METHODS: The authors provide a
      discussion of CA that seeks to introduce the various methods, issues, and
      considerations to the researcher who is largely unfamiliar with CA. A conceptual
      understanding of CA is guided through breaking down CA into a series of steps and
      issues to consider including composition of the dataset, selection of variables,
      decisions about standardizing variables, selecting a measure of association,
      selecting a clustering method, determining the number of clusters, and
      interpretation. RESULTS/CONCLUSIONS: Because the range of CA methods is diverse,
      and because the steps within each method are so varied, an attempt to offer a
      complete "how-to" process in a single article is imprudent. Rather, the novice
      reader will be able to use this article as a starting point for conducting his or
      her own particular CA study.

PMID- 18342819
TI  - Evaluating medication-related services in a hospital setting using the
      disconfirmation of expectations model of satisfaction.
AB  - BACKGROUND: Patient satisfaction is considered an important outcome measure of
      services and associated with behavioral intentions. The appraisal process
      commonly used in satisfaction models is the disconfirmation of expectations. A
      patient compares his or her experience to preexisting expectations. The resulting
      satisfaction from this comparison is dependent on whether the patient's
      expectations are superior, inferior, or just as expected. OBJECTIVES: The aims of
      this study were to (1) determine the relationship between disconfirmation of
      expectations with medication-related services and patient satisfaction with
      medical care; and (2) determine if patient satisfaction is related to the
      likelihood to say good things about the medical care provided at the hospital to
      family and friends. METHODS: A cross-sectional, nonexperimental study design was
      implemented to test the disconfirmation of expectations model. Patients on
      warfarin therapy and recently discharged from an acute care hospital to their
      homes were surveyed by mail. The survey asked about how well the hospital
      services related to medication therapy met patient expectations. Satisfaction
      with medical care and the likelihood of positive word of mouth regarding the
      medical care were also measured. Structural equation modeling (SEM) was used to
      test the model. RESULTS: The survey response rate was 34% (n=187). Factor
      analysis of the 7 disconfirmation of expectation items resulted in a 2-factor
      solution: (1) medication counseling and (2) discharge medication services. The
      SEM demonstrated that the model was significant; however, the disconfirmation of
      expectation items did not significantly relate to the 1-item satisfaction
      measure. Patient satisfaction and the behavioral intentions measures were
      significantly related. A post hoc analysis using SEM demonstrated that the
      disconfirmation of expectations factors did significantly relate to a higher
      order latent construct. This construct also related to patient satisfaction.
      CONCLUSION: The disconfirmation of expectations has a role in a postservice
      experience response expressed by the patient, but not as a direct antecedent to
      patient satisfaction. Opportunities to improve the model are the use of a multi
      item satisfaction measure and the inclusion of patient affect.

PMID- 18342820
TI  - Older adults' drug benefit beliefs: construct definition and measure development.
AB  - BACKGROUND: The Medicare Prescription Drug, Improvement and Modernization Act of
      2003 provides coverage of outpatient prescription drugs for Medicare
      beneficiaries. Although much has been learned since the program's implementation,
      a context within which this information can be understood is lacking. OBJECTIVE:
      The purpose of this study was to develop a reliable and valid multi-item
      instrument measuring beliefs about Medicare prescription drug benefits. METHODS:
      Survey items were generated using focus group transcripts, other surveys on the
      Medicare Part "D" program, and past studies of choice and satisfaction in drug
      insurance programs. Using data from the survey pilot test, item and reliability
      analyses were used to reduce and refine an initial pool of items. Data then were
      collected from a cross-sectional, mail survey of older adults living in
      Minnesota. Data were analyzed using exploratory factor analysis. Summated rating
      scales then were constructed and assessed further using reliability analyses.
      Construct validity of summated scales was examined by comparing scale scores
      across response categories of survey items that collected information on general
      political attitudes, perceptions of the Medicare Part "D" program, health status,
      and health care utilization and demographics. RESULTS: The adjusted response rate
      for the main survey was 55.98% (744/1329). Iterative factor analysis produced 2
      interpretable scales. The first, termed "access/equity" (13 items, Cronbach's
      alpha=0.89) measures beliefs that a Medicare drug benefit should both provide
      affordable prescription drugs for beneficiaries and do this in a manner that is
      equitable for all participants. The second, termed "comprehensibility" (6 items,
      Cronbach's alpha=0.80) assesses beliefs that regulations governing a Medicare
      drug benefit should be easily understood. Discriminant validity tests suggest
      that these measures behave in a manner consistent with related research in these
      areas. CONCLUSIONS: Measures of 2 facets of older adults' drug benefit beliefs
      were developed using a multiple step procedure. Future research could focus on
      developing a better understanding of other facets of these beliefs and sound
      methods of measurement.

PMID- 18342821
TI  - Association between diabetes patients' knowledge about medications and their
      blood glucose control.
AB  - BACKGROUND: Diabetes mellitus is a common chronic disorder frequently resulting
      in hyperglycemia and numerous long-term complications. Research has shown that
      improved glycemic control reduces the rate and number of diabetes-related
      complications. Evidence suggests that patients who are more knowledgeable about
      diabetes self-care may be more likely to achieve better glycemic control.
      OBJECTIVE: The purpose of this study is to determine the relationship between
      patients' knowledge about their diabetes medications and their blood glucose
      control. METHODS: Patients receiving oral pharmacologic treatment for type 2
      diabetes mellitus were asked to answer a short questionnaire assessing their
      knowledge about their medications. Patients were part of an ambulatory care
      practice in Baltimore, Maryland, that provides primary care medical services to
      an inner-city, predominantly African American population. A medication knowledge
      score (number of correct responses to 8 components) was tabulated and correlated
      to the most recent glycosylated hemoglobin (A1c) (drawn within the previous 90
      days). Multivariate models were constructed, with A1c as the outcome and
      patients' medication knowledge as the independent variable. Potential confounders
      included in the models were age, sex, education level, number of diabetes
      medications, and insurance status. RESULTS: Fifty patients were screened for the
      study; 44 agreed to participate and met inclusion criteria. Patients' diabetes
      medication knowledge scores ranged between 1 and 7, with a median score of 5.
      Older patients (65 years and older) and male patients scored lower than their
      counterparts. There was a strong inverse association between knowledge score and
      A1c (r=-0.61; P<.001). Glycosylated hemoglobin was one-half unit lower with each
      one-unit increase in knowledge score among men; among women A1c was 1.6 units
      lower for each one-unit increase in knowledge score. CONCLUSION: Patients with
      greater understanding and knowledge of their diabetes medications demonstrated
      better glycemic control. This cross-sectional association of medication knowledge
      and A1c was more pronounced in women than in men.

PMID- 18342822
TI  - Effects of repeated callbacks on response rate and nonresponse bias: results from
      a 17-state pharmacy survey.
AB  - BACKGROUND: Although surveys are the most common method of data collection in
      research in the social & behavioral pharmaceutical sciences, little evidence
      exists on pharmacists' and pharmacies' patterns of telephone survey participation
      and the impact of repeated callbacks on minimizing nonresponse bias. OBJECTIVES:
      To (1) describe final disposition of the survey sample, (2) describe the effect
      of repeated callbacks on response rate, and (3) examine whether hard-to-contact
      cases differ from those that are relatively easier to contact in terms of general
      pharmacy characteristics and characteristics specific to survey topics. METHODS:
      This study used a cross-sectional descriptive survey design that gathered
      information from key informants of 2558 community pharmacies in 17 states.
      Telephone interviews were conducted using a Computer Assisted Telephone Interview
      system. Final disposition of the sample units and the final response rate were
      reported. General pharmacy characteristics and characteristics specific to
      immunization delivery (ID) and emergency preparedness and response (EPR)
      activities were compared across different ease-of-contact levels. RESULTS: A
      total of 1707 pharmacies (66.7%) completed the interview; 757 (29.6%) were
      eligible cases that were not interviewed; 8 (0.3%) and 86 (3.4%) were cases of
      unknown eligibility and ineligibility, respectively. The final response rate was
      69.1%. The number of calls to pharmacies was most productive on the first 9 calls
      and leveled off after the 14th call. When comparing characteristics among
      different ease-of-contact levels, 2 out of 3 characteristics related to ID
      activities were different. No differences were found in general pharmacy
      characteristics and characteristics specific to EPR activities, however.
      CONCLUSION: The greater number of callbacks resulted in higher response rates due
      to greater number of completed interviews. The increase in response rate did not
      rule out nonresponse bias, however. Hard-to-contact cases differed from
      relatively easier to contact cases in terms of characteristics related to the
      survey topic, but not general characteristics.

PMID- 18342823
TI  - Pharmacists as health educators and risk communicators in the early detection of
      prostate cancer.
AB  - BACKGROUND: Community pharmacist involvement in health communication could assist
      in ameliorating health disparities in a number of areas. One such area is the
      early detection of prostate cancer in patients. OBJECTIVES: The primary goal of
      this study was to explore the role of pharmacists as health educators and risk
      communicators in the prevention of prostate cancer mortality. The study
      objectives were to (1) describe community pharmacists' attitudes and beliefs
      related to serving as health educators and risk communicators on prostate cancer;
      and (2) assess community pharmacists' knowledge about prostate cancer. METHODS: A
      cross-sectional survey methodology was used to collect data from pharmacists
      present at the Florida Pharmacy Association 115th Annual Meeting. Eighty-nine
      pharmacists were administered a survey to measure their knowledge, attitudes, and
      beliefs using a structured survey form. Descriptive statistics and multiple
      regression analyses were used to analyze participants' responses. RESULTS: The
      mean age of participants was 45 years and they were mostly male, White (non
      Hispanic) with B.S. Pharmacy as the highest degree. The face validity of the
      survey instrument was established through pilot test. Participants' views about
      offering prostate cancer education for patients were generally positive; however,
      participants' score on the general prostate cancer knowledge scale for patients
      was lower than expected for health care professionals, with approximately 45% of
      the participating pharmacists scoring less than 80% on the Odedina Prostate
      Cancer Screening Behavior Scale. Based on multiple regression analyses,
      participants' gender and disease state management status were found to be
      significantly associated with prostate cancer knowledge, whereas prostate cancer
      knowledge, technician staffing, and the type of pharmacy significantly predicted
      pharmacists' interest in prostate cancer education. CONCLUSIONS: Although the
      community pharmacists in this study were willing to take on responsibilities in
      the prevention and detection of prostate cancer, their knowledge base may serve
      as an impediment to action. Future research may identify means by which to
      educate pharmacists and enable their involvement.

PMID- 18342824
TI  - An evaluation of the validity of inferences made from 3 diabetes assessment
      instruments: a Rasch analysis.
AB  - BACKGROUND: Many patients who have diabetes lack adequate knowledge, positive
      attitudes, and sufficient resources to achieve optimal outcomes in the management
      of their disease. A key to assessing the impact of pharmacists' interactions with
      diabetes patients is the resultant impact on patient knowledge, attitudes, and
      satisfaction. As such, it is important that quality instruments be used to obtain
      accurate and dependable measures of these outcomes. OBJECTIVE: To evaluate the
      validity of inferences made from 3 separate diabetes instruments used in the
      assessment of patient knowledge, attitudes, and satisfaction. METHODS: This pilot
      study enrolled 30 patients with diabetes mellitus to evaluate the following 3
      instruments: (1) Check Your Hemoglobin A1CIQ, (2) the revised Diabetes
      Questionnaire, and (3) a satisfaction questionnaire. The instruments were used to
      assess patient knowledge of diabetes and diabetes-related complications,
      attitudes toward having diabetes mellitus, and satisfaction with the services
      provided in a pharmacist-run diabetes clinic, respectively. Rasch analysis was
      used to determine if the instruments were able to measure the concepts they are
      intended to measure when used in this sample. RESULTS: After evaluating the 3
      instruments, it was determined that Instrument 1 displayed construct
      underrepresentation and some mistargeting. Moreover, Instrument 2 demonstrated
      reasonably good rating scale function but exhibited construct underrepresentation
      and ceiling effects. Finally, Instrument 3 did not meet the necessary
      requirements for proper rating scale function and displayed ceiling effects and
      mistargeting. CONCLUSIONS: This pilot evaluation suggested that none of the
      instruments were useful in this population, which reinforces the need for
      researchers to use item response theories to examine the psychometric properties
      of instruments used in reporting various patient outcome measures. Pharmacists
      and other health care professionals should be alerted to potential problems with
      the validity of inferences made from underperforming instruments, so as to
      prevent inaccurate conclusions.

PMID- 18342825
TI  - HELLP syndrome: an atypical presentation.
AB  - HELLP syndrome without proteinuria or hypertension is rare. We present the case
      of a 33-year-old primigravid who initially was diagnosed with pulmonary embolism.
      The patient was readmitted with a diagnosis of subcapsular hematoma and
      eventually diagnosed with HELLP syndrome with a sequela of hepatic rupture.

PMID- 18342826
TI  - Inadequate screening in patients evaluated by nongynecologists for cervical
      cancer: a case control analysis.
AB  - OBJECTIVE: The purpose of this study was to determine the rate of unsatisfactory
      Papanicolaou tests between gynecology and nongynecology providers at a single
      institution. STUDY DESIGN: Vanderbilt University Medical Center data were used to
      obtain a list of all liquid-based cervical Papanicolaou smears that were
      collected between September 2002 and October 2006. Unsatisfactory samples were
      identified as 2 groups (gynecology vs nongynecology) for statistical comparison.
      RESULTS: There were 69,129 Papanicolaou smears that had been collected between
      September 2002 and October 2006; 47,165 smears were in the gynecology group, and
      21,964 smears were in the nongynecology group. Of these, 1206 smears were
      designated to be "unsatisfactory." A nongynecology provider was more likely to
      have an unsatisfactory Papanicolaou test result, compared with a gynecology
      physician (3% [602/21,964] vs 1% [604/47,165]; P < .001). The odds of having an
      unsatisfactory Papanicolaou test result was 2 times higher with nongynecology,
      compared with gynecology, physicians (odds ratio, 2.17; 95% CI, 1.94-2.43).
      CONCLUSION: Rates of liquid-based smears reported as unsatisfactory are higher
      among nongynecology providers. Competency-based learning programs might help to
      address this discrepancy.

PMID- 18342827
TI  - Dome-shaped macula in eyes with myopic posterior staphyloma.
AB  - PURPOSE: To describe an unusual feature in myopic eyes responsible for visual
      loss, which we call a dome-shaped macula. DESIGN: Retrospective, observational
      case series. METHODS: After observing isolated cases of dome-shaped macula, we
      analyzed optical coherence tomography (OCT) scans of 140 highly myopic eyes
      present in our OCT database to find similar cases. Fifteen eyes of 10 patients
      had a dome-shaped macula. These patients all had undergone fluorescein
      angiography (FA), indocyanine green angiography (ICGA), and B-scan
      ultrasonography examinations. RESULTS: The mean refractive error of the affected
      eyes was -8.25 diopters (D; range, -2 to -15 D). Median visual acuity was 20/50.
      Recent visual impairment was noted in 11 of the 15 eyes studied, and
      metamorphopsia was noted in eight eyes. Four eyes were asymptomatic. FA showed
      atrophic changes in the macular retinal pigment epithelium (RPE) in all eyes,
      combined with focal points of leakage in seven of the 15 eyes. The dome-shaped
      appearance of the macula was visible on both B-scan ultrasonography and OCT: a
      characteristic bulge of the macular retina, RPE, and choroid within the concavity
      of the moderate posterior staphyloma was present in all eyes. In 10 eyes, OCT
      also showed a shallow foveal detachment at the top of the dome-shaped macula.
      CONCLUSIONS: A dome-shaped macula within a myopic staphyloma is an unreported
      type of myopic posterior staphyloma. The dome-shaped macula often is associated
      with RPE atrophic changes and foveal retinal detachment, which may explain the
      visual impairment in these eyes.

PMID- 18342828
TI  - Primary vitrectomy without scleral buckling for pseudophakic rhegmatogenous
      retinal detachment.
AB  - PURPOSE: To report the anatomic and functional results of primary vitrectomy
      without scleral buckling for the treatment of pseudophakic rhegmatogenous retinal
      detachment (PsRD). DESIGN: Prospective, nonrandomized surgical technique study.
      METHODS: One hundred eyes of 98 patients with PsRD were operated by vitrectomy
      alone. Internal subretinal fluid drainage, cryocoagulation and/or endolaser and
      fluid-air exchange with sulfur hexafluoride 20% was applied in all cases. The
      preoperative and postoperative characteristics were analyzed. Main outcome
      measures were anatomic success rates after initial surgical intervention and
      after reoperation for primary failures, visual outcome at the last follow-up
      visit, and complications. RESULTS: Mean follow-up +/- standard deviation (SD) was
      12 +/- 6.3 months (range, seven to 36 months). Mean final visual acuity +/- SD
      was 0.42 +/- 0.45 logarithm of the minimum angle of resolution (logMAR) compared
      with 0.95 +/- 0.73 logMAR before surgery (P < .01). Mean number +/- SD of retinal
      breaks found before surgery was 1.36 +/- 1.12 (range, zero to five), and an
      additional 1.58 +/- 2.26 (range, zero to 15) retinal breaks were found during
      surgery. The retina was reattached successfully after a single surgery in 92 eyes
      (92%). Recurrence of retinal detachment occurred in eight eyes (8%), caused by
      proliferative vitreoretinopathy in six eyes (75%) and by new breaks in two eyes
      (25%). Final anatomic reattachment was obtained in these cases after a mean of
      1.75 subsequent operations. Three eyes required permanent silicone oil tamponade
      so that final anatomic success was achieved in 97 eyes (97%). The most common
      postoperative complication was ocular hypertonia of more than 21 mm Hg, observed
      in 36 (36%) eyes, which was managed successfully. CONCLUSIONS: Primary vitrectomy
      without scleral buckling provides a high anatomic success rate in eyes with PsRD
      and is associated with few complications.

PMID- 18342829
TI  - Photoreceptor inner and outer segment defects in myopic foveoschisis.
AB  - PURPOSE: To evaluate pathologic features of the photoreceptors in myopic
      foveoschisis with the Fourier-domain optical coherence tomography (FD-OCT).
      DESIGN: Observational case series. METHODS: Seventeen eyes of 15 patients with
      myopic foveoschisis (foveal detachment type, six eyes; foveoschisis type, 11
      eyes) were included. We observed the photoreceptor inner and outer segments
      (IS/OS) and evaluated the morphologic status using FD-OCT. Fundus photographs and
      time-domain OCT (TD-OCT) images also were obtained. RESULTS: IS/OS defects, which
      are uncommon in retinal detachments in eyes with myopia, were seen clearly in
      five eyes (three eyes [50%] with the foveal detachment type; two eyes [18%] with
      the foveal schisis type). Fundus photographs showed myopic chorioretinal atrophy
      in eight study eyes (47%), including diffuse atrophy in four eyes (24%) and
      patchy atrophy in four eyes (24%). The IS/OS defects on FD-OCT were accompanied
      by myopic chorioretinal atrophy in three (60%) of five eyes. CONCLUSIONS: FD-OCT
      enables observation of more detailed retinal structures in these myopic eyes. The
      IS/OS defects may be specific to, but are not rare, in myopic foveoschisis and
      may predict the postoperative visual recovery.

PMID- 18342830
TI  - Three-dimensional spectral-domain optical coherence tomography images of the
      retina in the presence of epiretinal membranes.
AB  - PURPOSE: To study the inner surface of the retina in the presence of epiretinal
      membranes (ERMs) using a prototype spectral-domain optical coherence tomography
      (SD-OCT) device. DESIGN: Small case series, performed in the Department of
      Ophthalmology, Bascom Palmer Eye Institute, Miller School of Medicine, University
      of Miami, from August 2005 through December 2006. METHOD: An 8-microm axial
      resolution SD-OCT instrument was used to scan the eyes of patients diagnosed with
      ERM. The ERM and the internal limiting membrane (ILM) were segmented separately
      to evaluate the traction caused by the ERM on the retina. It was then possible to
      reconstruct the ILM and ERM surfaces in 3-dimensional space and to obtain
      corresponding retinal thickness maps. RESULTS: SD-OCT B scans showed the points
      of attachment of the ERM to the ILM. Segmented surface maps of the ERM produced
      very smooth sheets, whereas those of the ILM presented wrinkles under and around
      the ERM. CONCLUSIONS: SD-OCT revealed the geometry of retinal traction in eyes
      with ERM and may be useful in understanding further the pathologic features of
      these lesions.

PMID- 18342831
TI  - Descemet stripping endothelial keratoplasty: effect of the surgical procedure on
      corneal optics.
AB  - PURPOSE: To determine the changes in corneal optical performance after posterior
      lamellar corneal transplantation. DESIGN: Retrospective case series. METHODS: The
      anterior segment in four eyes of four patients who underwent Descemet stripping
      endothelial keratoplasty (DSEK) with cataract extraction and intraocular lens
      (IOL) implantation were imaged with the Visante anterior segment optical
      coherence tomography [OCT] (Carl Zeiss Meditec, Dublin, California, USA). The
      curvature of the posterior surface of the donor graft was compared with that of
      the host cornea, and corneal thickness was measured. RESULTS: All eyes had a
      hyperopic refractive error after surgery. The posterior corneal curvature after
      surgery was more than that before surgery. Average preoperative keratometry was
      43.4 diopters (D), and after surgery, it was 42.8 D using keratometry. However,
      when the postsurgical corneal power was calculated using the Gaussian optics
      method, the average value was 40.8 D. CONCLUSIONS: The addition of a donor
      corneal graft to the posterior surface of decompensated corneas may lessen the
      effective optical power of the cornea and may have implications for IOL power
      calculations in these eyes.

PMID- 18342832
TI  - Stability of laser epithelial keratomileusis with and without mitomycin C
      performed to correct myopia in thin corneas: a 15-month follow-up.
AB  - PURPOSE: To study the stability of the refraction 15 months after myopic laser
      epithelial keratomileusis (LASEK) performed in thin corneas with and without
      adjuvant mitomycin C (MMC). DESIGN: Retrospective review. METHODS: One hundred
      and thirty-six consecutive eyes that had undergone LASEK to correct their myopia
      and that had a preoperative central corneal thickness (CCT) of <500 microm at
      Vissum Madrid, Spain, were included. Intraoperative MMC was applied when the
      ablation depth exceeded 50 microm (49 eyes). We compared the residual refraction
      between the three- and 15-month examinations to detect a possible myopic change
      that would suggest secondary corneal ectasia. RESULTS: Mean preoperative CCT +/-
      standard deviation (SD) was 484.4 +/- 11.8 microm (range, 440 to 499 microm).
      Mean CCT +/- SD three months after surgery was 417.9 +/- 32.1 microm (range, 339
      to 473 microm). Mean preoperative spherical refraction +/- SD was -3.49 +/- 2.10
      diopters (D). Mean preoperative cylinder +/- SD was -0.87 +/- 1.20 D. The mean
      residual sphere +/- SD was 0.15 +/- 0.40 D three months after surgery and 0.11 +/
      0.60 D 15 months after surgery (P = .45). The mean cylinder +/- SD was -0.13 +/-
      0.30 D and -0.25 +/- 0.50 D, respectively (P = .06). Both the uncorrected visual
      acuity (UCVA) and the best-spectacle corrected visual acuity (BSCVA) showed
      statistically significant improvement on the 15-month examination (P = .01 and P
      = .0001, respectively). When analyzed separately, the subgroup treated with
      intraoperative MMC also showed stability of the refraction and a statistically
      significant improvement both in UCVA and in BSCVA. Topography showed no signs of
      ectasia in any case. CONCLUSIONS: Myopic LASEK performed on thin corneas,
      regardless of the use of intraoperative MMC, seems to obtain stable refractive
      results, with no sign of ectasia during a 15-month follow-up.

PMID- 18342833
TI  - Unilateral ligature-induced periodontitis influences the expression of
      neuropeptides in the ipsilateral and contralateral trigeminal ganglion in rats.
AB  - OBJECTIVES: Expression of neuronal neuropeptides in inflammatory conditions is
      altered. The changes in expression of substance P (SP) and calcitonin gene
      related peptide (CGRP) in ipsilateral and contralateral trigeminal ganglion (TG)
      neurons were investigated by immunohistochemistry one week after unilateral
      ligature-induced periodontitis in rats. DESIGN: A retrograde nerve tracer
      Fluorogold (FG) was applied into the gingival sulcus of the second maxillary
      molar to identify the neurons in TG that specifically innervate the inflamed
      gingivomucosa. In addition, neurons from the corresponding maxillary and the
      adjacent mandibular-ophthalmic regions in TG were analysed. RESULTS:
      Statistically significantly higher frequencies of CGRP-positive neurons,
      regardless of their size, were found in TG ipsilateral to the periodontitis (83%
      and 73% in FG-labelled and maxillary regions, respectively) than in the control
      group without periodontitis (52% and 42% in FG-labelled and maxillary regions,
      respectively). The frequency of small FG-labelled SP-positive neurons in the
      ipsilateral TG (60%) was significantly higher than in the control TG (25%). In
      the contralateral TG the frequency of CGRP-positive neurons in maxillary region
      (66%) was significantly higher than in the control group. Surprisingly, the
      number of SP-positive neurons in all regions of contralateral TG decreased when
      compared to control and ipsilateral TGs. CONCLUSIONS: Taken together, these
      results implicate a role of neurogenic component in the pathogenesis of
      periodontitis. The contralateral response in the TG could be mediated through the
      transmedian neurological pathways crossing in the trigeminal nuclear complex or
      through the systemic inflammatory reaction and the activation of the so called
      "neuro-immune axis".

PMID- 18342834
TI  - Decision-making and risk aversion among depressive adults.
AB  - Depression is associated with behavioral avoidance of potentially rewarding
      environmental contexts. The present study examined the performance of depressive
      individuals and controls on a neuropsychological measure of decision-making that
      favors risk avoidance. Depressive (n=41) and control (n=44) participants were
      administered the Iowa Gambling Task, which measures the ability of participants
      to maximize earnings by choosing low-risk, low-reward responses over high-risk,
      high-reward responses. Results provided partial support for the hypothesis that
      depressive participants would learn to avoid risky responses faster than control
      participants. Depressive participants demonstrated better performance than
      controls, scoring higher than controls overall and showing a trend toward earning
      more money overall. However, the lack of an interaction between depressive status
      and time does not support the specific hypothesis of more rapid learning.
      Findings suggested enhanced feedback-based decision-making and risk aversion
      among depressive individuals.

PMID- 18342835
TI  - Overgeneral autobiographical memory predicts diagnostic status in depression.
AB  - Major depressive disorder (MDD) is characterised by difficulties in retrieving
      specific autobiographical memories, with a significant propensity towards
      categoric memories (i.e. memories of a summary type). Previous studies have
      demonstrated that this overgeneral memory is a valid predictor of the course of
      depression, with reduced specificity being associated with worse outcome. Most of
      these studies have employed continuous measures of depression to assess the
      course of the symptoms. This study investigated whether overgeneral memory also
      predicts clinical status at follow-up (i.e. whether patients still meet criteria
      for depression). Patients who fulfilled criteria for major depressive disorder
      were tested shortly after admission to the hospital and were retested some weeks
      later. It was found that lower levels of specificity or a higher number of
      categoric memories were associated with a higher probability of still being
      diagnosed with MDD. These memory variables outperformed other relevant indices,
      such as depression severity, rumination, level of self-esteem and dysfunctional
      attitudes.

PMID- 18342836
TI  - Histone deacetylase inhibitor SAHA induces ERalpha degradation in breast cancer
      MCF-7 cells by CHIP-mediated ubiquitin pathway and inhibits survival signaling.
AB  - Estrogen receptor alpha (ERalpha) plays an important role in the development and
      progression of breast cancer, and recent studies showed that ERalpha expression
      is associated with resistance to hormonal therapy. Therefore, a number of studies
      have explored ways to deplete ERalpha from breast cancer cells as a new therapy
      especially for hormone-refractory breast cancer. We reported here that
      suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor,
      effectively depletes ERalpha in breast cancer MCF-7 cells. However, the intrinsic
      mechanisms by which SAHA decreases ERalpha levels are not clear. Our present data
      demonstrated that both inhibition of ERalpha mRNA level and promotion of ERalpha
      degradation by the proteasome contribute to SAHA-induced ERalpha depletion,
      indicating that SAHA may exert its effects through transcriptional and
      posttranslational mechanisms. Furthermore, the decrease of ERalpha protein level
      in MCF-7 cells after SAHA treatment is mainly the result of its rapid degradation
      by the ubiquitin-proteasome pathway rather than transcriptional inhibition. In
      addition, we showed that inactivation of the heat shock protein-90 (Hsp90) is
      involved in SAHA-induced ERalpha degradation, and ubiquitin ligase CHIP (C
      terminal Hsc70 interacting protein) enhances SAHA-induced ERalpha degradation.
      SAHA-induced ERalpha depletion is paralleled with reduction of transcriptional
      activity of ERalpha and SAHA is able to effectively inhibit cell proliferation
      and induce apoptosis of MCF-7 cells. Taken together, our results revealed a
      mechanism for SAHA-induced ERalpha degradation and indicated that SAHA is a
      suitable pharmacological agent for depletion of ERalpha and a potential choice
      for breast cancer expressing high ERalpha.

PMID- 18342837
TI  - Changes in maternal liver Cyp2c and Cyp2d expression and activity during rat
      pregnancy.
AB  - During human pregnancy, CYP2C9, CYP2C19, and CYP2D6 activities are altered. The
      aim of the current study was to determine if this phenomenon can be replicated in
      the rat, and to evaluate the mechanisms that contribute to the changes in Cyp2c
      and Cyp2d activity during pregnancy. The intrinsic clearance of dextromethorphan
      O-demethylation, a measure of Cyp2d2 activity, was decreased 80% at both days 9
      and 19 of gestation when compared to non-pregnant controls. The decreased
      intrinsic clearance was a result of both decreased V(max) and increased K(m)
      values at both days of gestation. Quantitative RT-PCR revealed that transcripts
      of Cyp2d2 and Cyp2d4 were significantly decreased at day 19 of pregnancy (p<0.05)
      when compared to day 9 and non-pregnant controls. The decrease in Cyp2d mRNA
      levels correlated with a decrease in several nuclear receptor mRNA levels
      (RARalpha, RXRalpha, HNF1 and HNF3beta) but not with the mRNA levels of nuclear
      receptors usually associated with regulation of P450 enzymes (PXR, CAR and
      HNF4alpha). In contrast, Cyp2c12 and Cyp2c6 transcription and protein expression
      were not significantly altered during rat pregnancy although the intrinsic
      clearance of Cyp2c6 mediated diclofenac 4'-hydroxylation was increased 2-fold on
      day 19 of gestation when compared to non-pregnant controls. The increase in
      intrinsic clearance was due to a decrease in the K(m)-value for 4'
      hydroxydiclofenac formation. These data show that pregnancy significantly alters
      the expression and activity of drug metabolizing enzymes in an enzyme and
      gestational stage specific manner. These changes are likely to have toxicological
      and therapeutic implications.

PMID- 18342838
TI  - Inhibitory effect of fluoxetine on lymphoma growth through the modulation of
      antitumor T-cell response by serotonin-dependent and independent mechanisms.
AB  - Fluoxetine, a selective serotonin reuptake inhibitor, is widely used for the
      treatment of depressive symptoms of cancer patients. However, there are
      contradictory evidences about its effects on immunity and cancer. Thus, we
      studied the effects of fluoxetine on tumor growth and on antitumoral T-cell
      mediated immunity. In vivo chronic fluoxetine treatment inhibited tumor growth,
      and increased latency of appearance of solid tumors and survival of mice.
      Fluoxetine administration also increased mitogen-induced T-cell proliferation and
      Tumor Necrosis Factor-alpha (TNF-alpha) and Interferon-gamma (IFN-gamma)
      expression, without altering CD4(+)/CD8(+) ratio. In vitro, fluoxetine did not
      affect tumor cells proliferation, but it exerted a direct effect on T
      lymphocytes. Both fluoxetine and serotonin stimulated proliferation induced by a
      suboptimal mitogen concentration but inhibited proliferation at the optimal one.
      When both drugs were combined the results indicated that the effects of
      fluoxetine are in part independent of its ability to elevate serotonin
      extracellular levels. Finally, continue fluoxetine administration in nude mice -
      devoid of T lymphocytes - did not modify tumor progression, thus supporting the
      hypothesis of an immuno-modulatory effect of this drug on T cells that drives
      tumor growth control. These findings indicate, for the first time, that
      fluoxetine inhibits tumor growth through modulation of T-cell-mediated immunity
      by the already known serotonin-dependent pathway and by a novel independent
      mechanism.

PMID- 18342839
TI  - Food restriction enhances peak corticosterone levels, cocaine-induced locomotor
      activity, and DeltaFosB expression in the nucleus accumbens of the rat.
AB  - Chronic stress has been known to potentiate addictive behaviours in both human
      addicts and experimental animals. In the present study, chronic mild food
      restriction was used as a stressor to investigate its effect on the locomotor
      simulant effects of cocaine as well as FosB expression in the nucleus accumbens
      and caudate putamen. Chronic mild food restriction enhanced the locomotor
      response to the first cocaine injection, such that chronically food restricted
      animals showed a significant increase in activity upon an initial administration
      of 15 mg/kg of cocaine, an effect which only became apparent in control animals
      after repeated injections. Food restriction also increased expression of the 35
      37 kDa isoforms of DeltaFosB compared to free-fed rats. DeltaFosB proteins have
      been previously implicated in the rewarding effects of drugs of abuse and
      therefore their upregulation by the prolonged stress of food restriction suggests
      a possible mechanism for the enhancement of addictive behaviours by stress.

PMID- 18342840
TI  - Long-term administration of estrogen or tamoxifen to ovariectomized rats affords
      neuroprotection to hippocampal neurons by modulating the expression of Bcl-2 and
      Bax.
AB  - Recently we reported that chronic treatment with 17beta-estradiol (E2) or
      tamoxifen (TAM) regulates the ovariectomy-induced downregulation of the key
      molecules linked to hippocampal synaptic plasticity and signal transduction
      pathway. We now report modulation of the antiapoptotic (Bcl-2) and proapoptotic
      (Bax) proteins in the hippocampus of both the ovariectomized (OVX) rats as well
      as those given E2 or TAM subcutaneously as a daily dose for four weeks post
      ovariectomy. Forty bilaterally OVX animals were divided into four groups of 10
      each, namely i) OVX+E2 (0.1 mg/kg body weight), ii) OVX+TAM (0.05 mg/kg body
      weight), iii) OVX+vehicle (0.1 ml of sesame oil) and iv) OVX controls. An
      additional group of 10 animals constituted the ovary intact controls. Following
      culmination of treatment regimen, brain tissues of five animals from each group
      were processed for immunohistochemical staining of Bcl-2 and Bax on perfusion
      fixed cryo-sections. The remaining animals in each group were utilized for
      protein and Western blot analyses using unfixed hippocampal tissue. The results
      revealed that chronic administration of both E2 and TAM prevented the ovariectomy
      induced downregulation of Bcl-2 and upregulation of Bax expression while
      restoring the Bcl-2/Bax ratio as observed in the ovary intact rats. Furthermore,
      TUNEL assay demonstrated a decline in the percentage of TUNEL positive cells in
      E2 or TAM treated groups. Confocal microscope studies of ERalpha and the
      apoptotic markers revealed that these two proteins co-reside in the same ERalpha
      positive hippocampal neurons. Thus, long-term E2 or TAM therapy modulates the
      apoptotic proteins and affords neuroprotection to the hippocampal neurons.
      Furthermore the estrogen-like effects of TAM point towards its potential as a
      beneficial therapeutic agent for neurodegenerative disorders, particularly in the
      postmenopausal women.

PMID- 18342841
TI  - Striatal projections from the rat lateral posterior thalamic nucleus.
AB  - The dorsocentral striatum (DCS) has been implicated as an associative striatal
      area receiving inputs from several cortical areas including medial agranular
      cortex (AGm), posterior parietal cortex (PPC), and visual association cortex to
      form a cortical-subcortical circuit involved in directed attention and neglect.
      The lateral posterior thalamic nucleus (LP) may also play a role in directed
      attention and neglect because LP has robust reciprocal connections with these
      cortical areas and projects to DCS. We used anterograde axonal tracing to map
      thalamostriatal projections from LP and surrounding thalamic nuclei, with a focus
      on projections to DCS. The thalamic nuclei investigated included LP, laterodorsal
      thalamic nucleus (LD), central lateral nucleus (CL), and posterior thalamic
      nucleus (Po). We found that the mediorostral part of LP (LPMR) projects strongly
      to DCS as well as to the dorsal peripheral region of the striatum. Further, there
      is topography within LPMR and DCS such that the far medial LPMR projects to the
      central region of DCS (projection area of AGm) and the central LPMR projects to
      the dorsal region of DCS (projection area of PPC and Oc2M). In contrast, the
      laterorostral part of LP (LPLR) and other thalamic nuclei surrounding LP project
      to dorsolateral to dorsomedial peripheral regions of the striatum but do not
      project to DCS. These findings indicate that DCS is a region of convergence for
      thalamostriatal and corticostriatal projections from regions that are themselves
      interconnected, serving as the key element of the corticostriatal-thalamic
      network mediating spatial processing and directed attention.

PMID- 18342842
TI  - A journal of molecular, cellular and biochemical toxicology.

PMID- 18342843
TI  - On stent-graft models in thoracic aortic endovascular repair: a computational
      investigation of the hemodynamic factors.
AB  - In treating thoracic aortic diseases, endovascular repair involves the placement
      of a self-expanding stent-graft system across the diseased thoracic aorta.
      Computational fluid dynamic techniques are applied to model the blood flow by
      numerically solving the three-dimensional continuity equation and the time
      dependent Navier-Stokes equations for an incompressible fluid. From our results,
      high blood pressure level and high systolic slope of the pressure waveform will
      significantly increase the drag force on a stent-graft whereas high blood
      viscosity causes only a mild increase. It indicates that hemodynamic factors
      might have an important impact on the drag force and thus play a significant role
      in the risk of stent-graft failure.

PMID- 18342844
TI  - Lung nodule detection in low-dose and thin-slice computed tomography.
AB  - A computer-aided detection (CAD) system for the identification of small pulmonary
      nodules in low-dose and thin-slice CT scans has been developed. The automated
      procedure for selecting the nodule candidates is mainly based on a filter
      enhancing spherical-shaped objects. A neural approach based on the classification
      of each single voxel of a nodule candidate has been purposely developed and
      implemented to reduce the amount of false-positive findings per scan. The CAD
      system has been trained to be sensitive to small internal and sub-pleural
      pulmonary nodules collected in a database of low-dose and thin-slice CT scans.
      The system performance has been evaluated on a data set of 39 CT containing 75
      internal and 27 sub-pleural nodules. The FROC curve obtained on this data set
      shows high values of sensitivity to lung nodules (80-85% range) at an acceptable
      level of false positive findings per patient (10-13 FP/scan).

PMID- 18342845
TI  - Texture analysis on MRI images of non-Hodgkin lymphoma.
AB  - The aim here is to show that texture parameters of magnetic resonance imaging
      (MRI) data changes in lymphoma tissue during chemotherapy. Ten patients having
      non-Hodgkin lymphoma masses in the abdomen were imaged for chemotherapy response
      evaluation three consecutive times. The analysis was performed with MaZda texture
      analysis (TA) application. The best discrimination in lymphoma MRI texture was
      obtained within T2-weighted images between the pre-treatment and the second
      response evaluation stage. TA proved to be a promising quantitative means of
      representing lymphoma tissue changes during medication follow-up.

PMID- 18342846
TI  - Cis-regulatory organization of the Pax6 gene in the ascidian Ciona intestinalis.
AB  - The Pax6 gene has attracted intense research interest due to its apparently
      important role in the development of eyes and the central nervous system (CNS) in
      many animal groups. Pax6 is also of interest for comparative genomics since it
      has not been duplicated in tetrapods, making for a direct orthology between the
      Ciona intestinalis gene CiPax6 and Pax6 in mammals. CiPax6 has been shown to be
      expressed in the anterior brain, caudal nerve cord, and in parts of the brain
      associated with the photoreceptive ocellus. This information was extended here
      using in-situ hybridization, and shows that CiPax6 transcripts mark the lateral
      regions of the nerve cord, remarkably similar to Pax6 expression in the mouse. As
      a means of dissecting the cis-regulation of CiPax6 we tested 8 kb of sequence
      using transient reporter transgene assays. Three separate regions were found that
      work together to drive the overall CiPax6 expression pattern. A 211 bp sequence 2
      kb upstream of the first exon was found to be a major enhancer driving expression
      in the sensory vesicle (the anterior portion of the ascidian brain). Other
      upstream sequences were shown to work with the sensory vesicle enhancer to drive
      expression in the remainder of the CNS. An "eye enhancer" was localized to the
      first intron, which controls specific expression in the central portion of the
      sensory vesicle, including photoreceptor cells. The fourth intron was found to
      repress ectopic expression of the reporter gene in middle portions of the
      embryonic brain. Aspects of this overall regulatory organization are similar to
      the organization of the Pax6 homologs in mice and Drosophila, particularly the
      presence of intronic elements driving expression in the eye, brain and nerve
      cord.

PMID- 18342847
TI  - Ca2+/Calmodulin-dependent kinase II signaling causes skeletal overgrowth and
      premature chondrocyte maturation.
AB  - The long bones of vertebrate limbs originate from cartilage templates and are
      formed by the process of endochondral ossification. This process requires that
      chondrocytes undergo a progressive maturation from proliferating to postmitotic
      prehypertrophic to mature, hypertrophic chondrocytes. Coordinated control of
      proliferation and maturation regulates growth of the skeletal elements. Various
      signals and pathways have been implicated in orchestrating these processes, but
      the underlying intracellular molecular mechanisms are often not entirely known.
      Here we demonstrated in the chick using replication-competent retroviruses that
      constitutive activation of Calcium/Calmodulin-dependent kinase II (CaMKII) in the
      developing wing resulted in elongation of skeletal elements associated with
      premature differentiation of chondrocytes. The premature maturation of
      chondrocytes was a cell-autonomous effect of constitutive CaMKII signaling
      associated with down-regulation of cell-cycle regulators and up-regulation of
      chondrocyte maturation markers. In contrast, the elongation of the skeletal
      elements resulted from a non-cell autonomous up-regulation of the Indian hedgehog
      responsive gene encoding Parathyroid-hormone-related peptide. Reduction of
      endogenous CaMKII activity by overexpressing an inhibitory peptide resulted in
      shortening of the skeletal elements associated with a delay in chondrocyte
      maturation. Thus, CaMKII is an essential component of intracellular signaling
      pathways regulating chondrocyte maturation.

PMID- 18342848
TI  - Misty somites, a maternal effect gene identified by transposon-mediated
      insertional mutagenesis in zebrafish that is essential for the somite boundary
      maintenance.
AB  - Somite boundary formation is crucial for segmentation of vertebrate somites and
      vertebrae and skeletal muscle morphogenesis. Previously, we developed a Tol2
      transposon-mediated gene trap method in zebrafish. In the present study, we aimed
      to isolate transposon insertions that trap maternally-expressed genes. We found
      that homozygous female fish carrying a transposon insertion within a maternally
      expressed gene misty somites (mys) produced embryos that showed obscure somite
      boundaries at the early segmentation stage (12-13 hpf). The somite boundaries
      became clear and distinct after this period and the embryos survived to
      adulthood. This phenotype was rescued by expression of mys cDNA in the homozygous
      adults, confirming that it was caused by a decreased mys activity. We analyzed a
      role of the mys gene by using morpholino oligonucleotides (MOs). The MO-injected
      embryo exhibited severer phenotypes than the insertional mutant probably because
      the mys gene was partially active in the insertional mutant. The MO-injected
      embryo also showed the obscure somite boundary phenotype. Fibronectin and
      phosphorylated FAK at the intersomitic regions were accumulated at the boundaries
      at this stage, but, unlike wild type embryos, somitic cells adjacent to the
      boundaries did not undergo epithelialization, suggesting that Mys is required for
      epithelialization of the somitic cells. Then in the MO-injected embryos, the
      boundaries once became clear and distinct, but, in the subsequent stages,
      disappeared, resulting in abnormal muscle morphogenesis. Accumulation of
      Fibronectin and phosphorylated FAK observed in the initial stage also
      disappeared. Thus, Mys is crucial for maintenance of the somite boundaries formed
      at the initial stage. To analyze the mys defect at the cellular level, we placed
      cells dissociated from the MO-injected embryo on Fibronectin-coated glasses. By
      this cell spreading assay, we found that the mys-deficient cells reduced the
      activity to form lamellipodia on Fibronectin while FAK was activated in these
      cells. Thus, we demonstrate that a novel gene misty somites is essential for
      epithelialization of the somitic cells and maintenance of the somite boundary.
      Furthermore, Mys may play a role in a cellular pathway leading to lamellipodia
      formation in response to the Fibronectin signaling. We propose that the Tol2
      transposon mediated gene trap method is powerful to identify a novel gene
      involved in vertebrate development.

PMID- 18342849
TI  - Sox8 is a critical regulator of adult Sertoli cell function and male fertility.
AB  - Sox8 encodes a high-mobility group transcription factor that is widely expressed
      during development. Sox8, -9 and -10 form group E of the Sox gene family which
      has been implicated in several human developmental disorders. In contrast to
      other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly
      showed only idiopathic weight loss and reduced bone density. The careful analysis
      of our Sox8 null mice, however, revealed a progressive male infertility
      phenotype. Sox8 null males only sporadically produced litters of reduced size at
      young ages. We have shown that SOX8 protein is a product of adult Sertoli cells
      and its elimination results in an age-dependent deregulation of spermatogenesis,
      characterized by sloughing of spermatocytes and round spermatids, spermiation
      failure and a progressive disorganization of the spermatogenic cycle, which
      resulted in the inappropriate placement and juxtaposition of germ cell types
      within the epithelium. Those sperm that did enter the epididymides displayed
      abnormal motility. These data show that SOX8 is a critical regulator of adult
      Sertoli cell function and is required for both its cytoarchitectural and
      paracrine interactions with germ cells.

PMID- 18342850
TI  - Cancer incidence among pesticide applicators exposed to trifluralin in the
      Agricultural Health Study.
AB  - Trifluralin, 2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline, is a 2,6-dinitro
      herbicide widely used to control annual grasses and broadleaf weeds in
      agricultural settings. The association between trifluralin use and common cancer
      incidence was evaluated among 50,127 private and commercial pesticide applicators
      in the Agricultural Health Study (AHS), a prospective cohort study of licensed
      pesticide applicators and their spouses in Iowa and North Carolina. Poisson
      regression was used to examine internal dose-response relationships, while
      controlling for important lifestyle factors and other agricultural exposures. Two
      metrics of exposure (lifetime days and intensity-weighted lifetime days) were
      used in exposure-response analyses with non-exposed applicators, as well as
      applicators in the lowest tertile of exposure, as reference groups. Incident
      cancers were identified through state tumor registries from enrollment in 1993
      through 2002. Trifluralin exposure was not associated with cancer incidence
      overall among 51% of private and commercial applicators (n=25,712) who had used
      trifluralin. However, there was an excess of colon cancer in the exposure
      category of higher half of highest tertile (rate ratios (RR) of 1.76 (95% CI=1.05
      2.95) using the non-exposed as a referent and 1.93 (95% CI=1.08-3.45) using those
      with the lowest tertile of exposure as the referent). There was also a non
      significantly elevated risk for kidney cancer and bladder cancer in the highest
      exposure group, although only the kidney cancer finding was consistent across
      exposure metrics. Although there was a possible link between trifluralin exposure
      and colon cancer, small numbers and inconsistencies in dose-response and subgroup
      analyses indicate that this may be a chance finding.

PMID- 18342851
TI  - Putting the diet back into diet-induced obesity: diet-induced hypothalamic gene
      expression.
AB  - A wealth of detailed mechanistic information relating to obesity and body weight
      regulation has emerged from study of single gene mutation models, and continues
      to be generated by engineered rodent models targeting specific genes. However, as
      an early step in translational research, many researchers are turning to models
      of diet-induced obesity. Interpretation of data generated from such models is not
      aided by the variety of diets and rodent strains employed in these studies and a
      strong case could be made for rationalisation. Differences in experimental
      protocol, which may deploy a single obligatory solid diet, a choice of solid
      diets, or liquid/solid combinations, and which may or may not allow a preferred
      macronutrient composition to be selected, mean that different models of diet
      induced obesity achieve that obesity by different routes. The priority should be
      to mimic the palatability- and choice-driven over-consumption that probably
      underlies the majority of human obesity. Some of the hypothalamic energy balance
      genes apparently 'recognise' developing diet-induced obesity as indicated by
      counter-regulatory changes in expression levels. However, substantial changes in
      gene expression on long-term exposure to obesogenic diets are not able to prevent
      weight gain. Forebrain reward systems are widely assumed to be overriding
      hypothalamic homeostatic energy balance systems under these circumstances. More
      mechanism-based research at the homeostatic/reward/diet interface may enable
      diets to be manipulated with therapeutic benefit, or define the contribution of
      these interactions to susceptibility to diet-induced obesity.

PMID- 18342853
TI  - Transporter associated with antigen processing (TAP) 1 gene polymorphisms in
      patients with hypersensitivity pneumonitis.
AB  - Hypersensitivity pneumonitis (HP) is a lung inflammatory disease caused by the
      inhalation of a variety of antigens. Previous studies support the role of the
      major histocompatibility complex (MHC) class II genes in the susceptibility to
      develop HP. However, the putative role of other MHC loci has not been elucidated.
      Transporters associated with antigen processing (TAP) genes are located within
      the MHC class II region and play an important role transporting peptides across
      the endoplasmic reticulum membrane for MHC class I molecules assembly. The
      distribution of single nucleotide polymorphisms (SNPs) in TAP1 genes was analyzed
      in 73 hypersensitivity pneumonitis (HP) patients and 58 normal subjects. We found
      a significant association of the allele Gly-637 (GGC) (p=0.00004, OR=27.30,
      CI=3.87-548.04) and the genotypes Asp-637/Gly-637 (p=0.01, OR=16.0, CI=2.19
      631.21), Pro-661/Pro-661 (p=0.006, OR=11.30, CI=2.28-75.77) with HP. A
      significant decrease in the frequency of the allele Pro-661 (CCA) (p=0.008,
      OR=0.06, CI=0-0.45), the genotype Asp-637/Asp-637 (p=0.01, OR=0.17, 95% CI=0.05
      0.58) and the haplotype [Val-333 (GTC), Val-458 (GTG), Gly-637 (GGC), Pro-661
      (CCA)] was detected in HP patients compared with controls (p=0.002, OR=0.07,
      CI=0.0-0.57). These findings suggest that TAP1 gene polymorphisms are related to
      HP risk, and highlight the importance of the MHC in the development of this
      disease.

PMID- 18342852
TI  - Synaptic physiology of central CRH system.
AB  - Corticotropin-Releasing Hormone (CRH) or Corticotropin-Releasing Factor (CRF) and
      its family of related naturally occurring endogenous peptides and receptors are
      becoming recognized for their actions within central (CNS) and peripheral (PNS)
      nervous systems. It should be recognized that the term 'CRH' has been displaced
      by 'CRF' [Guillemin, R., 2005. Hypothalamic hormones a.k.a. hypothalamic
      releasing factors. J. Endocrinol. 184, 11-28]. However, to maintain uniformity
      among contributions to this special issue we have used the original term, CRH.
      The term 'CRF' has been associated recently with CRH receptors and designated
      with subscripts by the IUPHAR nomenclature committee [Hauger, R.L., Grigoriadis,
      D.E., Dallman, M.F., Plotsky, P.M., Vale, W.W., Dautzenberg, F.M., 2003.
      International Union of Pharmacology. XXXVI. Corticotrophin-releasing factor and
      their ligands. Pharmacol. Rev. 55, 21-26] to denote the type and subtype of
      receptors activated or antagonized by CRH ligands. CRH, as a hormone, has long
      been identified as the regulator of basal and stress-induced ACTH release within
      the hypothalamo-pituitary-adrenal axis (HPA axis). But the concept, that CRH and
      its related endogenous peptides and receptor ligands have non-HPA axis actions to
      regulate CNS synaptic transmission outside the HPA axis, is just beginning to be
      recognized and identified [Orozco-Cabal, L., Pollandt, S., Liu, J., Shinnick
      Gallagher, P., Gallagher, J.P., 2006a. Regulation of Synaptic Transmission by CRF
      Receptors. Rev. Neurosci. 17, 279-307; Orozco-Cabal, L., Pollandt, S., Liu, J.,
      Vergara, L., Shinnick-Gallagher, P., Gallagher, J.P., 2006b. A novel rat medial
      prefrontal cortical slice preparation to investigate synaptic transmission from
      amygdala to layer V prelimbic pyramidal neurons. J. Neurosci. Methods 151, 148
      158] is especially noteworthy since this synapse has become a prime focus for a
      variety of mental diseases, e.g. schizophrenia [Fischbach, G.D., 2007. NRG1 and
      synaptic function in the CNS. Neuron 54, 497-497], and neurological disorders,
      e.g., Alzheimer's disease [Bell, K.F., Cuello, C.A., 2006. Altered synaptic
      function in Alzheimer's disease. Eur. J. Pharmacol. 545, 11-21]. We suggest that
      "The Stressed Synapse" has been overlooked [c.f., Kim, J.J., Diamond, D.M. 2002.
      The stressed hippocampus, synaptic plasticity and lost memories. Nat. Rev.,
      Neurosci. 3, 453-462; Radley, J.J., Morrison, J.H., 2005. Repeated stress and
      structural plasticity in the brain. Ageing Res. Rev. 4, 271-287] as a major
      contributor to many CNS disorders. We present data demonstrating CRH
      neuroregulatory and neuromodulatory actions at three limbic synapses, the
      basolateral amygdala to central amygdala synapse; the basolateral amygdala to
      medial prefrontal cortex synapse, and the lateral septum mediolateral nucleus
      synapse. A novel stress circuit is presented involving these three synapses. We
      suggest that CRH ligands and their receptors are significant etiological factors
      that need to be considered in the pharmacotherapy of mental diseases associated
      with CNS synaptic transmission.

PMID- 18342854
TI  - Identification of a repeated domain within mammalian alpha-synemin that interacts
      directly with talin.
AB  - The type VI intermediate filament (IF) protein synemin is a unique member of the
      IF protein superfamily. Synemin associates with the major type III IF protein
      desmin forming heteropolymeric intermediate filaments (IFs) within developed
      mammalian striated muscle cells. These IFs encircle and link all adjacent
      myofibrils together at their Z-lines, as well as link the Z-lines of the
      peripheral layer of cellular myofibrils to the costameres located periodically
      along and subjacent to the sarcolemma. Costameres are multi-protein assemblies
      enriched in the cytoskeletal proteins vinculin, alpha-actinin, and talin. We
      report herein a direct interaction of human alpha-synemin with the cytoskeletal
      protein talin by protein-protein interaction assays. The 312 amino acid insert
      (SNTIII) present only within alpha-synemin binds to the rod domain of talin in
      vitro and co-localizes with talin at focal adhesion sites within mammalian muscle
      cells. Confocal microscopy studies showed that synemin co-localizes with talin
      within the costameres of human skeletal muscle cells. Analysis of the primary
      sequences of human alpha- and beta-synemins revealed that SNTIII is composed of
      seven tandem repeats, each containing a specific Ser/Thr-X-Arg-His/Gln (S/T-X-R
      H/Q) motif. Our results suggest human alpha-synemin plays an essential role in
      linking the heteropolymeric IFs to adherens-type junctions, such as the
      costameres within mammalian striated muscle cells, via its interaction with
      talin, thereby helping provide mechanical integration for the muscle cell
      cytoskeleton.

PMID- 18342855
TI  - The PERK/eIF2 alpha signaling pathway of Unfolded Protein Response is essential
      for N-(4-hydroxyphenyl)retinamide (4HPR)-induced cytotoxicity in cancer cells.
AB  - N-(4-hydroxyphenyl)retinamide (4HPR) is a synthetic retinoid that has been tested
      in clinical trials as a cancer chemopreventive drug. 4HPR is cytotoxic to cancer
      cells but the underlying molecular mechanisms are at present only partially
      understood. Here we demonstrate that in the human cervical cancer cell line HeLa
      and the human leukemia cell line HL-60, 4HPR caused rapid, Reactive Oxygen
      Species (ROS)-dependent activation of the Unfolded Protein Response (UPR). In
      HeLa cells, 4HPR was shown to induce cell death and activation of procaspases.
      These effects of 4HPR could be abolished by the over-expression of dominant
      negative mutants of PERK or eIF2 alpha. HeLa cells incubated with 4HPR were found
      to form autophagosomes that were also mediated by the PERK/eIF2 alpha pathway.
      While 4HPR-induced cell death could be significantly prevented by the presence of
      specific caspase inhibitors, 3-methyladenine (3-MA) that inhibits autophagosome
      formation enhanced 4HPR-induced cell death. Examination of individual 4HPR
      treated HeLa cells revealed that those without the development of autophagosomes
      hence exhibiting an incomplete UPR were caspase-active and were not viable, while
      those with autophagosomes were caspase-inactive and retained cell viability. Our
      data suggest that the PERK/eIF2 alpha pathway is essential for the cytotoxicity
      of 4HPR that targets on cancer cells with malfunctional UPR.

PMID- 18342856
TI  - Lens diameter and thickness as a function of age and pharmacologically stimulated
      accommodation in rhesus monkeys.
AB  - Uncertainty exists regarding accommodative and age changes in lens diameter and
      thickness in humans and monkeys. In this study, unaccommodated and accommodated
      refraction, lens diameter, and lens thickness were measured in rhesus monkeys
      across a range of ages. Iridectomized eyes were studied in 33 anesthetized
      monkeys aged 4-23 years. Refraction was measured using a Hartinger coincidence
      refractometer and lens thickness was measured with A-scan ultrasound. Lens
      diameters were measured with image analysis from slit-lamp images captured via a
      video camera while a saline filled, plano perfusion lens was placed on the
      cornea. Accommodation was pharmacologically stimulated with 2% pilocarpine via
      the perfusion lens in 21 of the monkeys and lens diameters were measured until a
      stable minimum was achieved. Refraction and lens thickness were measured again
      after the eye was accommodated. Unaccommodated lens thickness increased linearly
      with age by 0.029 mm/year while unaccommodated lens diameter showed no systematic
      change with age. Accommodative amplitude decreased by 0.462 D/year in response to
      pilocarpine. The accommodative increase in lens thickness decreased with age by
      0.022 mm/year. The accommodative decrease in lens diameter declined linearly with
      age by 0.021 mm/year. Rhesus monkeys undergo the expected presbyopic changes
      including increasing lens thickness and a decreasing ability of the lens to
      undergo changes in thickness and diameter with accommodation, however without an
      age-related change in unaccommodated lens diameter. As in humans, the age-related
      decrease in accommodative amplitude in rhesus monkeys cannot be attributed to an
      age-related increase in lens diameter.

PMID- 18342857
TI  - Comparison of daily and alternate day recombinant follicle-stimulating hormone
      stimulation protocols for intrauterine insemination.
AB  - OBJECTIVE: To determine the efficacy of daily versus alternate-day stimulation
      for patients undergoing intrauterine insemination (IUI). DESIGN: Retrospective
      comparative study. SETTING: University tertiary care center for infertility.
      PATIENT(S): Women with anovulatory or unexplained infertility for over 12 months
      who had not responded to or not conceived with clomiphene citrate treatment.
      INTERVENTION(S): Ovarian stimulation with recombinant follicle-stimulating
      hormone (FSH; follitropin-beta) given either daily or on alternate days before
      IUI. MAIN OUTCOME MEASURE(S): Clinical pregnancy at ultrasound 4 weeks after IUI.
      Secondary outcome measures were duration of stimulation, total gonadotropin dose,
      ovarian response, and multiple pregnancy rate. RESULT(S): Of the 212 women who
      underwent a first cycle of gonadotropin stimulation, 28 had daily injections and
      117 had alternate-day injections of follitropin-beta only for IUI. Female age,
      antral follicle count, and day-3 serum FSH were comparable. The median duration
      of stimulation (8 days vs. 8 days) and the median number of follicles over 14 mm
      (3.5 vs. 3.0) were similar in both groups. However, the total recominbinant FSH
      dose (825 vs. 625 IU) and endometrial thickness (10.1 vs. 9.3 mm) were greater in
      the daily injection group. The clinical pregnancy rate per cycle was 42% (12 out
      of 28) in the daily injection group and 19% (22 out of 117) in the alternate-day
      group. CONCLUSION(S): Daily recombinant FSH stimulation for IUI seems to be
      associated with a higher clinical pregnancy rate than alternate-day FSH
      stimulation. Prospective randomized trials would be needed to determine whether
      this is indeed the case.

PMID- 18342858
TI  - Ultrasound-guided transvaginal ovarian needle drilling (UTND) for treatment of
      polycystic ovary syndrome: a randomized controlled trial.
AB  - OBJECTIVE: To evaluate the outcome of ovarian needle drilling using transvaginal
      ultrasound guidance as an alternative to the traditional laparoscopic
      electrosurgical drilling for patients with polycystic ovary syndrome (PCOS).
      DESIGN: A randomized controlled study. SETTING: University teaching hospital and
      private practice setting. PATIENT(S): The study comprised 163 patients with
      clomiphene-resistant PCOS. INTERVENTION(S): Patients were randomly allocated to
      either treatment with ultrasound-guided transvaginal needle ovarian drilling
      (UTND; n = 82) or laparoscopic electrosurgery ovarian drilling (n = 81). MAIN
      OUTCOME MEASURE(S): Hormonal changes (FSH, LH, T), ovulation and pregnancy.
      RESULT(S): There were no significant differences between the two groups with
      regard to body mass index, hormonal profiles, clinical manifestations, and
      ultrasound findings of PCOS. The duration of UTND was 15.3 +/- 5.61 minutes (10.5
      22.3 minutes), while it was 25.6 +/- 8.2 minutes (20.3-38.1 minutes) in
      laparoscopic drilling, with a statistically significant difference between the
      two groups. There were no significant differences between the two groups with
      regard to resumption of normal menstruation, hirsutism, acne, ovulation, and
      pregnancy. UTND resulted in significant improvement in the ovulation, pregnancy,
      hirsutism, and acne. There were significant decreases in the serum LH and T
      levels but not in the FSH or LH/FSH levels after UTND as well. CONCLUSION(S):
      UTND can be adopted as an outpatient office procedure. The ease of scheduling,
      reduced costs, and rapid recovery suggest it as a first-line treatment for PCOS
      cases resistant to clomiphene citrate.

PMID- 18342859
TI  - Sex-reversed phenotype in association with two novel mutations c.2494delA and
      c.T3004C in the ligand-binding domain of the androgen receptor gene.
AB  - OBJECTIVE: To establish the diagnosis of complete androgen insensitivity syndrome
      (CAIS) in two patients with characteristic clinical and hormonal findings,
      relative family history in one of them, and unusual Mullerian remnants in the
      other. DESIGN: Case report. SETTING: Research laboratory in the Department of
      Medical Genetics at a university children's hospital. PATIENT(S): Two patients
      with 46,XY sex reversal and two maternal aunts of the first patient with the same
      clinical condition were tested. INTERVENTION(S): Bilateral gonadectomy was
      performed on both patients. MAIN OUTCOME MEASURE(S): Genetic counseling, cancer
      prophylaxis, hormone substitution therapy. RESULT(S): Molecular analysis revealed
      two novel mutations, a frameshift familial (c.2494delA) in patient 1 and a
      missense sporadic (c.T3004C) in patient 2. The c.2494delA mutation was also
      detected in two of the three affected maternal aunts of patient 1. Patient 2
      presents an unusual persistence of Mullerian structures. CONCLUSION(S): Genetic
      counseling of potential women carriers of androgen receptor (AR) mutations is
      crucial for the early diagnosis of the affected offspring. The presence of
      Mullerian remnants, although rare, should not exclude the diagnosis of CAIS. Both
      identified mutations are novel and provide further evidence for the correlation
      between specific AR mutations and phenotype.

PMID- 18342860
TI  - Effect of smoking on blood lead levels in workers and role of reactive oxygen
      species in lead-induced sperm chromatin DNA damage.
AB  - OBJECTIVE: To investigate whether cigarette smoking affects the blood lead levels
      (BLL) and whether exposure to lead introduces sperm chromatin DNA damage in
      factory workers. DESIGN: Cross-sectional study. SETTING: A battery plant in
      Taiwan. PATIENT(S): Eighty male workers employed within a battery plant.
      INTERVENTION(S): Standard semen analysis was performed according to the World
      Health Organization guidelines. MAIN OUTCOME MEASURE(S): Assessment of BLL, sperm
      chromatin DNA structure, reactive oxygen species generation and other
      conventional parameters of semen quality. RESULT(S): As compared with nonsmoking
      workers, the BLL were found to be considerably higher among smokers.
      Statistically significant differences were found in the sperm DNA denaturation
      (alphaT) induction and the percentage of sperm with increased DNA denaturation
      (COMP alphaT) in workers with moderate BLL (>or=25 microg/dL). After adjustment
      for smoking propensity, a positive correlation was discernible between BLL and
      alphaT, COMP alphaT, and morphologic abnormality. Furthermore, alphaT and COMP
      alphaT were also found to have positive correlations with sperm superoxide anion
      production. CONCLUSION(S): Workers with higher BLL were found to be at a higher
      risk of sperm morphologic abnormality and chromatin DNA integrity. These data are
      significant because they can facilitate the estimation of lead exposure in
      reproductive toxicology.

PMID- 18342861
TI  - Inhibitory effect of chicken gonadotropin-releasing hormone II on food intake in
      the goldfish, Carassius auratus.
AB  - Gonadotropin-releasing hormone (GnRH) is an evolutionarily conserved neuropeptide
      with 10 amino acid residues, which possesses some structural variants. A
      molecular form known as chicken GnRH II ([His(5) Trp(7) Tyr(8)] GnRH, cGnRH II)
      is widely distributed in vertebrates, and has recently been implicated in the
      regulation of sexual behavior and food intake in an insectivore, the musk shrew.
      However, the influence of cGnRH II on feeding behavior has not yet been studied
      in model animals such as rodents and teleost fish. In this study, therefore, we
      investigated the role of cGnRH II in the regulation of feeding behavior in the
      goldfish, and examined its involvement in food intake after
      intracerebroventricular (ICV) administration. ICV-injected cGnRH II at graded
      doses, from 0.1 to 10 pmol/g body weight (BW), induced a decrease of food
      consumption in a dose-dependent manner during 60 min after treatment. Cumulative
      food intake was significantly decreased by ICV injection of cGnRH II at doses of
      1 and 10 pmol/g BW during the 60-min post-treatment observation period. ICV
      injection of salmon GnRH ([Trp(7) Leu(8)] GnRH, sGnRH) at doses of 0.1-10 pmol/g
      BW did not affect food intake. The anorexigenic action of cGnRH II was completely
      blocked by treatment with the GnRH type I receptor antagonist, Antide. However,
      the anorexigenic action of cGnRH II was not inhibited by treatment with the
      corticotropin-releasing hormone (CRH) 1/2 receptor antagonist, *-helical CRH((9
      41)), and the melanocortin 4 receptor antagonist, HS024. These results suggest
      that, in the goldfish, cGnRH II, but not sGnRH, acts as an anorexigenic factor,
      as is the case in the musk shrew, and that the anorexigenic action of cGnRH II is
      independent of CRH- and melanocortin-signaling pathways.

PMID- 18342862
TI  - The effect of glucocorticoids on bradykinesia induced by immobilization stress.
AB  - It is well known that the release of glucocorticoids from the adrenal gland is
      increased in response to many types of stressors and plays a principal role in
      stress responses. We have shown that the synthesis of prostaglandins (PGs) in the
      brain is increased under several stress conditions including immobilization
      (IMO), and that endogenous glucocorticoids counteract this stress-induced PG
      synthesis. It was also recently reported that IMO damages dopaminergic (DA)
      neurons in the substantia nigra (SN), which is known to cause symptoms similar to
      Parkinson's disease (PD). The present study was therefore undertaken to determine
      the role of glucocorticoids in modulating the signs of PD induced by IMO. The
      pole test, in which each mouse was placed head upward at the top of a pole and
      the time taken to turn downward and to arrive on the floor was recorded, and
      immunohistochemistry for tyrosine hydroxylase (TH) in the SN were performed to
      evaluate bradykinesia and injury of DA neurons, respectively. Intact and
      adrenalectomized (ADX) mice were immobilized for 2 h twice, 1 day apart. Both
      bradykinesia and a decrease in the number of TH-immunoreactive cells in the SN
      were observed in ADX mice, but not in intact mice, following IMO. These effects
      of IMO on ADX mice were restored by treatment with corticosterone or
      indomethacin, a PG synthesis inhibitor. These results suggest that
      glucocorticoids play a role in preventing the detrimental effect of IMO on nigral
      DA neurons and resulting bradykinesia, and that this effect of IMO involves PG
      mediated mechanisms.

PMID- 18342863
TI  - Synchronous early-stage endometrial and ovarian cancer.
AB  - OBJECTIVE: To explore the clinicopathologic findings and oncological outcome of
      early-stage synchronous endometrial and ovarian malignancies. METHODS: A
      retrospective study of 93 women with synchronous stage I ovarian and stage I-II
      endometrial cancer treated between December 1981 and August 2005 in the
      gynecologic oncology department of San Gerardo Hospital, Italy. RESULTS: Fifty
      one percent of the ovarian tumors were stage Ia and 71% of the endometrial
      cancers had minimal myometrial invasion. Endometrioid histology and grade 2
      disease were prevalent in both sites. Hyperplasia and endometriosis coexisted in
      71% and 22% of endometrial and ovarian cancers, respectively. The actuarial 5
      year disease-free and overall survival rates were 83% and 96%, respectively.
      CONCLUSION: The incidence of synchronous endometrial and ovarian cancer is not
      negligible, especially among young women. Synchronous cancers show very favorable
      pathologic features and have an excellent oncologic outcome. Adjuvant therapy
      should be tailored according to surgical staging and histology.

PMID- 18342864
TI  - Assessment of coronary heart disease risk by combined analysis of coagulation
      factors.
AB  - OBJECTIVE: Prospective studies have reported a positive association of
      coagulation factors with risk of coronary heart disease (CHD). It is unclear
      whether these coagulation factors interact. METHODS AND RESULTS: Using a
      prospective case-cohort design, we analyzed by Cox proportional hazard regression
      interactions between soluble thrombomodulin (sTM) and fibrinogen, factor VIII
      (FVIII), FVII, or plasminogen activator inhibitor-1 (PAI-1) in 410 CHD cases and
      721 non-cases from the Atherosclerosis Risk in Communities (ARIC). There was a
      significant interaction between sTM and fibrinogen (p=0.027). We next assessed
      risk ratios (RR) by combined tertile analysis. Combined analysis revealed that
      being in the upper sTM tertile counteracted the CHD risk imposed by higher
      fibrinogen whereas being in the lower sTM tertile amplified the CHD risk of
      higher fibrinogen. sTM and fibrinogen mutually influenced CHD incidence in a
      concentration-dependent manner. When analyzed as single factors by tertiles,
      FVIII, FVII and PAI-1 were not associated with CHD. However, when analyzed
      together with sTM, FVIII and PAI-1 were both positively associated with CHD for
      those in the lower sTM tertile. CONCLUSION: There is a complex interaction
      between sTM and prothrombotic coagulation factors. Combined analysis improves CHD
      risk assessment.

PMID- 18342865
TI  - Effect of voluntary activation on age-related muscle fatigue resistance.
AB  - Ageing is associated with a higher fatigue resistance during submaximal or
      maximal fatiguing contractions. The present study aimed to investigate the
      contribution of the central and peripheral fatigue to the age-related differences
      in fatigue development of the plantar flexor muscles. Therefore, the voluntary
      activation, rest twitch moment and voluntary plantar flexor moment were examined
      before during as well as 2, 5 and 10min after a fatiguing task. This consisted of
      intermittent isometric submaximal plantar flexor contractions at equal intensity
      for both young and old adults (considering the age-related differences in muscle
      inhibition). Consequently, possible differences between young and old adults in
      voluntary activation during the maximal contraction utilised for determining the
      intensity of the fatiguing task, which can influence fatigue development, have
      been taken into account. The plantar flexors moment was calculated using inverse
      dynamics and the voluntary activation was measured using the twitch interpolation
      technique. Changes in voluntary activation and rest twitch moment during the
      fatiguing task were used to assess central and peripheral fatigue, respectively.
      In both young and old adults, peripheral ( approximately 20%) as well as central
      fatigue ( approximately 9%) contributed to the time to task failure. Old adults
      demonstrated greater time to task failure than young ones, but similar voluntary
      activation behaviour during the fatiguing task. We concluded that, the age
      related enhancement in fatigue resistance is not attributable to voluntary
      activation but is linked to mechanisms located within the working muscle.

PMID- 18342866
TI  - Comments on "Measurement of the microstructural fracture toughness of cortical
      bone using indentation fracture".

PMID- 18342867
TI  - Analysis of trace contamination of phthalate esters in ultrapure water using a
      modified solid-phase extraction procedure and automated thermal desorption-gas
      chromatography/mass spectrometry.
AB  - The present study was aimed to develop a procedure modified from the conventional
      solid-phase extraction (SPE) method for the analysis of trace concentration of
      phthalate esters in industrial ultrapure water (UPW). The proposed procedure
      allows UPW sample to be drawn through a sampling tube containing hydrophobic
      sorbent (Tenax TA) to concentrate the aqueous phthalate esters. The solid trap
      was then demoisturized by two-stage gas drying before subjecting to thermal
      desorption and analysis by gas chromatography-mass spectrometry. This process
      removes the solvent extraction procedure necessary for the conventional SPE
      method, and permits automation of the analytical procedure for high-volume
      analyses. Several important parameters, including desorption temperature and
      duration, packing quantity and demoisturizing procedure, were optimized in this
      study based on the analytical sensitivity for a standard mixture containing five
      different phthalate esters. The method detection limits for the five phthalate
      esters were between 36 ng l(-1) and 95 ng l(-1) and recovery rates between 15%
      and 101%. Dioctyl phthalate (DOP) was not recovered adequately because the
      compound was both poorly adsorbed and desorbed on and off Tenax TA sorbents.
      Furthermore, analyses of material leaching from poly(vinyl chloride) (PVC) tubes
      as well as the actual water samples showed that di-n-butyl phthalate (DBP) and
      di(2-ethylhexyl) phthalate (DEHP) were the common contaminants detected from PVC
      contaminated UPW and the actual UPW, as well as in tap water. The reduction of
      DEHP in the production processes of actual UPW was clearly observed, however a
      DEHP concentration of 0.20 microg l(-1) at the point of use was still being
      quantified, suggesting that the contamination of phthalate esters could present a
      barrier to the future cleanliness requirement of UPW. The work demonstrated that
      the proposed modified SPE procedure provided an effective method for rapid
      analysis and contamination identification in UPW production lines.

PMID- 18342868
TI  - Effect of silane reagent functionality for fluorinated alkyl and phenyl silica
      bonded stationary phases prepared in supercritical carbon dioxide.
AB  - This research examines the effect of silane reagent functionality for the
      preparation of fluorinated alkyl silica-bonded stationary phases prepared using
      supercritical carbon dioxide (sc-CO(2)) as a bonding medium. We present results
      that demonstrate that alkyl (C(8) and C(10)) and phenyl (pentafluorophenylpropyl,
      PFPP) silica bonded stationary phases can be prepared under sc-CO(2) conditions
      of 100 degrees C, 414bar and 3h, with surface coverages comparable to those
      obtained using organic solvent based methods. Fluorinated alkyl silica bonded
      phase preparation with a trichloro silane generates high ligand densities and
      more chemically uniform silica surface species compared to phases prepared using
      a monochloro or alkoxy silanes, as evidenced by thermogravimetric analysis (TGA)
      and (29)Si cross polarisation magic angle spinning (CP-MAS) NMR spectroscopy. In
      addition, the sc-trichloro prepared fluorinated C(8) bonded phases have
      demonstrated the ability to separate solutes on the basis of their molecular
      shape with the separation of the LC column shape selectivity test mixture, SRM
      869a in the elution order of PhPh<BaP=TBN with a selectivity value of
      alpha(TBN/BaP)=1.0. These chromatographic findings are indicative of a
      fluorinated C(8) silica bonded stationary phase that is capable of some shape
      recognition.

PMID- 18342869
TI  - Chiral separation of hydroxyflavanones in cyclodextrin-modified capillary zone
      electrophoresis using sulfated cyclodextrins as chiral selectors.
AB  - Chiral separations of three hydroxyflavanone aglycones, including 2'-, 3'-, and
      4'-hydroxyflavanone, in capillary zone electrophoresis (CZE) using randomly
      sulfate-substituted beta-cyclodextrin (S-beta-CD) or dual cyclodextrin (CD)
      systems consisting of S-beta-CD and a neutral CD at low pH were investigated. The
      results indicate that S-beta-CD is an excellent chiral selector for
      enantioseparation of 2'-hydroxyflavanone and is a good chiral selector for 3'
      hydroxyflavanone. Depending on the concentration of S-beta-CD ranging from 2.0 to
      0.75% (w/v), the enantioresolution values were 10.5-19.5 and 1.8-3.4 for 2'- and
      3'-hydroxyflavanone, respectively. The enantiomers of 4'-hydroxyflavanone could
      be effectively separated with S-beta-CD at a concentration of 2.0% (w/v) within
      20 min. The enantioselectivity and enantioresolution follow the order 2'
      hydroxyflavanone>>3'-hydroxyflavanone>4'-hydroxyflavanone. Alternatively, with
      the addition of sodium dodecyl sulfate (SDS) monomers at low concentrations in
      the electrophoretic system, enantioselectivity of these hydroxyflavanone
      aglycones could be enhanced with dual CD systems. In this case, SDS monomer acted
      as a complexing agent probably first with S-beta-CD and then subsequently with
      the analytes for increasing the effective electrophoretic mobility of the
      analytes towards the anode and as a selectivity controller for affecting the
      selectivity of hydroxyflavanones. Better enantioseparation between 2'
      hydroxyflavanone and 3'-hydroxyflavanone could be achieved with a dual CD system
      consisting of S-beta-CD and gamma-CD than that with S-beta-CD and beta-CD. In
      addition, possible chiral recognition mechanisms of hydroxyflavanones are
      discussed.

PMID- 18342870
TI  - In-line system containing porous polymer monoliths for protein digestion with
      immobilized pepsin, peptide preconcentration and nano-liquid chromatography
      separation coupled to electrospray ionization mass spectroscopy.
AB  - The use of two different monoliths located in capillaries for on-line protein
      digestion, preconcentration of peptides and their separation has been
      demonstrated. The first monolith was used as support for covalent immobilization
      of pepsin. This monolith with well-defined porous properties was prepared by in
      situ copolymerization of 2-vinyl-4,4-dimethylazlactone and ethylene
      dimethacrylate. The second, poly(lauryl methacrylate-co-ethylene dimethacrylate)
      monolith with a different porous structure served for the preconcentration of
      peptides from the digest and their separation in reversed-phase liquid
      chromatography mode. The top of the separation capillary was used as a
      preconcentrator, thus enabling the digestion of very dilute solutions of proteins
      in the bioreactor and increasing the sensitivity of the mass spectrometric
      detection of the peptides using a time-of-flight mass spectrometer with
      electrospray ionization. Myoglobin, albumin, and hemoglobin were digested to
      demonstrate feasibility of the concept of using the two monoliths in-line.
      Successive protein injections confirmed both the repeatability of the results and
      the ability to reuse the bioreactor for at least 20 digestions.

PMID- 18342871
TI  - AFM relative stiffness measurement of the plasticising effect of a non-ionic
      surfactant on plant leaf wax.
AB  - An AFM relative stiffness technique was applied to reconstituted Beta vulgaris L.
      wax films. Consecutive force arrays (n=100) made on the waxy surface at the same
      locations showed that there was no relative change in surface elasticity and this
      information was used as a reference to further experimental measurements. A
      surfactant solution was subsequently dropped on the waxy surface and the same
      array of indents was made at the same location as the reference test. The plant
      wax surface showed a reduction in its surface elasticity properties. The study
      has demonstrated that the AFM technique could be used to undertake a systematic
      assessment of the plasticising effects of agrochemicals on native and
      reconstituted plant wax films.

PMID- 18342872
TI  - Electrochemical and electrochemiluminescence study of Ru(bpy)(2+)3-doped silica
      nanoparticles with covalently grafted biomacromolecules.
AB  - Spherical Ru(bpy)(2+)(3)-doped silica (RuSi) nanoparticles were prepared via a
      water-in-oil microemulsion approach. The electrochemical and
      electrochemiluminescent properties of the RuSi nanoparticles immobilized on an
      indium tin oxide (ITO) electrode were investigated. Further,
      electrochemiluminescence (ECL) of the RuSi nanoparticles with covalently coated
      biomacromolecules was studied. By covalent cross-linking with glutaraldehyde,
      gamma-(aminopropyl) triethoxysilane (APTES)-pretreated RuSi nanoparticles were
      coupled with different concentrations of bovine serum albumin (BSA), hemoglobin,
      and myoglobin, respectively. ECL from these biomacromolecule-coated RuSi
      nanoparticles decreased with the increase of the loading of biomacromolecules.
      Moreover, the ECL of coreactants with different sizes was studied. The ECL
      decrease could be assigned to the steric hindrance and limited diffusion of
      coreactant molecules into the RuSi nanoparticles after biomacromolecule
      conjugation. Since tens of thousands of Ru(bpy)(2+)(3) molecules are contained in
      the silica particles and the RuSi nanoparticle surface modification could improve
      their biocompatibility, the biomacromolecule-coated RuSi nanoparticles could be
      readily used as efficient and stable ECL tag materials in the future.

PMID- 18342873
TI  - Hydrodynamic control of droplet division in bifurcating microchannel and its
      application to particle synthesis.
AB  - We describe herein a microfluidic system for active and precise control of
      droplet division at a bifurcation point in a microchannel. Water-in-oil or oil-in
      water droplets, which were initially formed at a T-junction, were introduced into
      the bifurcation point, and then divided into two daughter droplets. By
      continuously introducing 'tuning flow' into the downstream of one of the branch
      channels, and by controlling the flow rates distributed into the two branch
      channels, the sizes of the daughter droplets could be precisely tuned. The ratio
      of the volumetric flow rates into the branch channels was estimated by regarding
      the microchannel network as a resistive circuit. In addition, we performed
      synthesis of monodispersed polymer particles with controlled sizes utilizing the
      presented system. The ability to hydrodynamically control the droplet sizes will
      open new possibilities not only for producing useful emulsions, but also for
      conducting controlled chemical and biochemical reactions in a confined space.

PMID- 18342874
TI  - Site-selective time-resolved laser fluorescence spectroscopy of Eu3+ in calcite.
AB  - Three samples of calcite homogeneously doped with Eu(3+) were synthesized in a
      mixed-flow reactor. By means of selective excitation of the 5D0-->7F0 transition
      at low temperatures (T<20 K), three different Eu(3+) species (species A, B, and
      C, respectively) could be discriminated. For each one, the emission spectrum and
      lifetime were obtained after selective excitation of the single species. On the
      basis of these data, species C could be identified as Eu(3+) incorporated into
      the calcite lattice on the (nearly) octahedral Ca(2+) site. Species B was also
      identified as Eu(3+) incorporated into the calcite lattice, but the ligand field
      shows a much weaker symmetry. Species A, however, is not incorporated into the
      crystal's bulk, having 1-2 H(2)O ligands left in its first coordination sphere
      and showing very little symmetry, and is considered as Eu(3+) adsorbed onto the
      calcite surface. The emission spectra of species C for Eu:calcite grown in the
      presence of Na(+) were found to differ from those of Eu:calcite synthesized in
      the presence of K(+). The latter revealed a strong distortion in site symmetry,
      which was not observed in the samples grown in Na(+) solutions. This finding
      provides spectroscopic evidence in favor of an incorporation mechanism based on
      the charge-balanced coupled substitution of Na(+)+Eu(3+)<-->2Ca(2+).

PMID- 18342875
TI  - Micellar behavior of aqueous solutions of dodecyldimethylethylammonium bromide,
      dodecyltrimethylammonium chloride and tetradecyltrimethylammonium chloride in the
      presence of alpha-, beta-, HPbeta- and gamma-cyclodextrins.
AB  - Conductivity, static fluorescence and (1)H NMR measurements have been carried out
      to study the micellar behavior of aqueous solutions of
      dodecyldimethylethylammonium bromide (DDAB), dodecyltrimethylammonium chloride
      (DTAC) and tetradecyltrimethylammonium chloride (TDAC) in absence and presence of
      alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), hydroxypropyl-beta
      cyclodextrin (HPbeta-CD) and gamma-cyclodextrin (gamma-CD). The conductivity
      measurements were carried out at 298.15 K. The influence of cyclodextrins on the
      micellar parameters, such as cmc* (apparent critical micellar concentration),
      beta (degree of ionization) have been analyzed. Thermodynamics of the systems was
      discussed in terms of the change in standard free energy of micellization,
      DeltaG(m)(0). Micellization was found to be less spontaneous in presence of
      cyclodextrins. The fluorescence intensity of the surfactant solutions is enhanced
      by the addition of cyclodextrins. The association constants obtained from
      conductivity and fluorescence data suggest the binding of gamma-CD with the
      surfactants to be strongest among all the cyclodextrins used. (1)H NMR chemical
      shift changes provide powerful means for probing the cyclodextrin-micellar
      interactions and inclusion of surfactant is shown by the change in the chemical
      shift of some of the guest and host protons in comparison with the chemical
      shifts of the same protons in the free compounds.

PMID- 18342876
TI  - Dielectric and electrical properties of electrorheological carbon suspensions.
AB  - Measurements of electrorheological (ER) effects, dielectric properties, and
      electrical conductivity are made on an ER suspension composed of carbonaceous
      particles and silicone oil to understand the mechanism which governs the ER
      effect. In the frequency dependence of the dielectric permittivities, a
      dielectric dispersion is observed in the first-order dielectric permittivity,
      while in the third-order dielectric permittivity a resonance peak, which is due
      to shear-induced particle rotation, is recognized, showing that such dielectric
      properties are closely related to ER properties of the suspension. An electrical
      conduction mechanism, which is responsible for the ER effect, is also
      investigated from the dependence of dc electrical conductivity on electric-field
      strength and temperature.

PMID- 18342877
TI  - Histopathological classification of lesions observed in natural cases of
      paratuberculosis in free-ranging fallow deer (Dama dama).
AB  - Ninety-five adult fallow deer, legally hunted in the Regional Hunting Reserve of
      El Sueve (Northern Spain), were subjected to a post-mortem examination for
      paratuberculosis, samples being taken from the proximal and distal jejunum,
      proximal and distal ileum, ileocaecal valve and associated lymph nodes. The
      lesions were divided into four categories. Focal lesions (n=19 cases) consisted
      of small granulomas, mainly in the jejunal and ileal lymph nodes. Multifocal
      lesions (n=4) consisted of well-demarcated granulomas in the intestinal lymphoid
      tissue and also in the intestinal lamina propria. Diffuse multibacillary lesions
      (n=2) were characterized by a severe granulomatous enteritis and lymphadenitis.
      Macrophages and numerous Langhans giant cells containing many mycobacteria were
      present, resulting in macroscopical changes in the normal gut morphology. These
      changes were found from the proximal jejunum to the ileocaecal valve, but lesions
      were always particularly severe in the distal jejunum. In diffuse intermediate
      (multibacillary-lymphocytic) lesions (n=3) the infiltrate consisted of
      lymphocytes, macrophages and Langhans giant cells, with small numbers of
      mycobacteria. Mycobacterium avium subspecies paratuberculosis was identified by a
      polymerase chain reaction technique. The widespread occurrence of
      paratuberculosis in fallow deer in this Reserve represents a potential source of
      infection for other susceptible species.

PMID- 18342878
TI  - Left-sided intraventricular conduction delay concealed by right bundle branch
      block.
AB  - The electrocardiograms of a 69-year-old woman with severe heart failure showed a
      left-sided nonspecific intraventricular conduction delay (QRS duration, 0.13
      seconds) characterized by notches and slurrings in the descending part of the R
      waves in the left precordial leads and in the ascending parts of the S waves in
      the right precordial leads. Subsequently, a complete right bundle branch block
      with wider QRS complexes (0.17 seconds) appeared. It is possible to consider that
      the left-sided nonspecific intraventricular conduction delay was concealed by the
      greater conduction delay occurring when the complete right bundle branch block
      was present. This would be in keeping with a previous study using Doppler tissue
      imaging in which this was postulated but where the corresponding
      electrocardiograms were not shown.

PMID- 18342879
TI  - Thresholds in the relationship between mortality and left ventricular hypertrophy
      defined by electrocardiography.
AB  - BACKGROUND: Electrocardiographic criteria for the diagnosis of left ventricular
      hypertrophy in current use were defined using autopsy results or
      echocardiography; criteria defined using mortality might be more clinically
      meaningful. METHODS: Using data from Third National Health and Nutrition
      Examination Survey (NHANES III), we selected electrocardiographic measures that
      best differentiated those surviving at 5 years from those who did not. We
      identified voltage thresholds using regression techniques and then compared
      survival for subjects above and below the thresholds. RESULTS: Cornell voltage,
      Cornell product, and Novacode estimate of left ventricular mass index were
      discriminative for mortality and had identifiable thresholds present in their
      relationships with mortality. Independent of systolic blood pressure, there were
      significant associations with 5-year mortality for Novacode index above
      threshold; hazard ratios were 1.58 for women and 1.27 for men, and for 5-year
      cardiovascular mortality were 1.78 for women and 2.34 for men. CONCLUSIONS:
      Electrocardiographic criteria for left ventricular hypertrophy validated against
      mortality might be clinically useful.

PMID- 18342880
TI  - False ST elevation in a modified 12-lead surface electrocardiogram.
AB  - Precise recording of the standard 12-lead electrocardiogram (ECG) is technically
      time consuming. Placing limb leads on the torso has the major advantages of ease
      of use, increased speed of application, and decreased artifact. This modified ECG
      frequently substitutes for the standard 12-lead ECG in intensive care units to
      detect ischemia, although its implementation should be limited to interpreting
      arrhythmias. We describe a patient who was misdiagnosed with acute inferior
      myocardial infarction in a modified 12-lead ECG. To the best of our knowledge,
      this is the first case report regarding detection of false ST elevations in this
      setting. Always, a standard 12-lead ECG is recommended to evaluate any ST-T
      changes.

PMID- 18342881
TI  - Heart rate turbulence and other autonomic risk markers for arrhythmia risk
      stratification in dilated cardiomyopathy.
AB  - BACKGROUND: Noninvasive arrhythmia risk stratification in patients with
      nonischemic dilated cardiomyopathy (DCM) using autonomic markers have yielded
      disappointing results. Heart rate turbulence is a new method to assess cardiac
      autonomic function. AIM: The aim of the study was to compare the predictive value
      of heart rate turbulence with those of conventional autonomic risk markers for
      ventricular tachyarrhythmic events in patients with DCM. METHODS: The predictive
      value of heart rate turbulence, baroreflex sensitivity (phenylephrine method),
      and heart rate variability was assessed in patients with symptomatic congestive
      heart failure due to DCM who were in sinus rhythm and had a 24-hour Holter
      recording. Patients were followed for a combined end point of ventricular
      tachyarrhythmic events. RESULTS: A total of 114 patients (mean left ventricular
      ejection fraction, 28 +/- 11%), included in the Frankfurt DCM database between
      1996 and 2000, fulfilled the criteria for inclusion in this study. Determinate
      test results were obtained for heart rate variability in 98%, for baroreflex
      sensitivity in 90%, and for heart rate turbulence in 75% of patients (P = .008).
      Correlation between the different autonomic markers were only modest (r values,
      0.36-0.43). During a follow-up of 22 +/- 17 months, an end point event occurred
      in 15 patients. On univariate analysis, left ventricular ejection fraction and
      baroreflex sensitivity were significant predictors of arrhythmic events. On
      multivariate analysis, only baroreflex sensitivity remained an independent
      predictor (chi(2) = 3.17; P = .07). CONCLUSION: Reliable analysis of heart rate
      turbulence is possible in approximately 75% of eligible patients with DCM.
      Whereas blunted baroreflex sensitivity is a predictor of arrhythmic events, heart
      rate variability and turbulence do not yield predictive power in these patients.

PMID- 18342882
TI  - Spontaneous alternans in Brugada ST-segment morphology within minutes.
AB  - Brugada syndrome is an inherited, life-threatening, cardiac channelopathy where
      the electrocardiogram (ECG) characteristically depicts a classic pattern of
      complete or incomplete right bundle-branch block with ST-segment elevation in the
      right precordial leads V(1) to V(3). These, almost inalienable, ECG patterns may
      be dynamic, where changes may resolve to baseline or one particular type may
      evolve into another. Such alternans has been described with fever, electrolyte
      imbalances, atrial pacing, glucose and/or insulin administration, psychotropic
      drugs, beta-adrenergic blocker use, class IA and IC antiarrhythmic provocation
      testing, such as with ajmaline, procainamide, or flecainide, and even large
      meals, that is, "full stomach sign." However, spontaneous alternans between the
      different types of Brugada ECG patterns (types) have not been reported within
      minutes, in the absence of previously described precipitating factors. We present
      a novel case where classic, type 2, Brugada-like ECG pattern evolved
      spontaneously to type 1 before returning to type 2 within minutes of
      presentation.

PMID- 18342883
TI  - Longitudinal dissociation and concealed electrotonic conduction as a possible
      mechanism of AV block.

PMID- 18342884
TI  - Heterotypic trans-interaction of LI- and E-cadherin and their localization in
      plasmalemmal microdomains.
AB  - Cadherins are calcium-dependent adhesion molecules important for tissue
      morphogenesis and integrity. LI-cadherin and E-cadherin are the two prominent
      cadherins in intestinal epithelial cells. Whereas LI-cadherin belongs to the
      subfamily of 7D (seven-domain)-cadherins defined by their seven extracellular
      cadherin repeats and short intracellular domain, E-cadherin is the prototype of
      classical cadherins with five extracellular domains and a highly conserved
      cytoplasmic part that interacts with catenins and thereby modulates the
      organization of the cytoskeleton. Here, we report a specific heterotypic trans
      interaction of LI- with E-cadherin, two cadherins of distinct subfamilies. Using
      atomic force microscopy and laser tweezer experiments, the trans-interaction of
      LI- and E-cadherin was characterized on the single-molecule level and on the
      cellular level, respectively. This heterotypic interaction showed similar binding
      strength (20-52 pN at 200-4000 nm/s) and lifetime (0.8 s) as the respective
      homotypic interactions of LI- and E-cadherin. VE-cadherin, another classical
      cadherin, did not bind to LI-cadherin. In enterocytes, LI-cadherin and E-cadherin
      are located in different membrane regions. LI-cadherin is distributed along the
      basolateral membrane, whereas the majority of E-cadherin is concentrated in
      adherens junctions. This difference in membrane distribution was also reflected
      in Chinese hamster ovary cells stably expressing either LI- or E-cadherin. We
      found that LI-cadherin is localized almost exclusively in cholesterol-rich
      fractions, whereas E-cadherin is excluded from these membrane fractions. Given
      their different membrane localization in enterocytes, the heterotypic trans
      interaction of LI- and E-cadherin might play a role during development of the
      intestinal epithelium when the cells do not yet have elaborate membrane
      specializations.

PMID- 18342885
TI  - The integrity of the sarcin/ricin domain of 23 S ribosomal RNA is not required
      for elongation factor-independent peptide synthesis.
AB  - The elongation stage of protein synthesis consists of repeated cycles of the
      binding of aminoacyl-tRNA, peptide bond formation, and translocation. The process
      is normally catalyzed by the elongation factors Tu and G; however, the reactions
      can proceed, at least in prescribed and limited circumstance, in the absence of
      the elongation factors, a finding that strongly implies that the chemistry of
      protein synthesis is inherent in the ribosome. The sarcin/ricin domain in 23 S
      rRNA, the site of inactivation of ribosomes by ribotoxins, is where the
      elongation factors bind. The question that arises is whether the sarcin/ricin
      domain is necessary for factor-independent peptide synthesis. The answer is that
      it is not. The disruption of the sarcin/ricin domain by covalent modification
      with either sarcin or pokeweed antiviral protein did not affect factor
      independent peptide synthesis; nor did lethal mutations of nucleotides that
      abolish the binding of elongation factors. The results imply that the sole
      function of the sarcin/ricin domain is to provide a binding site for the
      elongation factors and, hence, to facilitate the elongation reactions. The
      results also raise the possibility of the co-evolution of the sarcin/ricin domain
      and the elongation factors.

PMID- 18342886
TI  - Solution structure and dynamics of peptidyl-tRNA hydrolase from Mycobacterium
      tuberculosis H37Rv.
AB  - Eubacterial peptidyl-tRNA hydrolase is an essential enzyme that hydrolyzes
      peptidyl-tRNAs that are released into the cytoplasm because of premature
      termination of translation, expression of minigenes, and action of lincosamide
      and macrolide antibiotics. This averts the arrest of protein synthesis caused by
      depletion of free tRNA. Recently, we demonstrated that Mycobacterium tuberculosis
      peptidyl-tRNA hydrolase (MtPth) is present in the cytosol of mycobacterium and is
      capable of hydrolyzing peptidyl-tRNA. Here, we present the solution structure of
      MtPth, which is the first solution structure for this family of proteins. MtPth
      typically consists of seven-stranded mixed beta-sheet surrounded by six alpha
      helices. The backbone dynamics for this enzyme were probed by measuring (15)N
      relaxation parameters and these were analyzed with model-free formalism and
      reduced spectral density mapping analysis. Overall, the protein molecule has
      tau(m) of 9.67+/-0.02 ns. The (15)N relaxation data analysis reveals that while
      majority of the protein backbone is rigid to motions, a short segment consisting
      of enzymatically critical residue H22, the loop-helix cover over the active site
      crevice, and the C-terminal helical hairpin exhibit motions on the milli-to
      microsecond timescale, all of which are linked to interaction with the substrate
      peptidyl-tRNA.

PMID- 18342887
TI  - Characterization of ligand-binding properties of the human BMP type II receptor
      extracellular domain.
AB  - ActR-IIA, ActR-IIB, and BMPR-II are low-affinity type II receptors that bind bone
      morphogenetic proteins (BMPs) in the same overall manner. The binding of BMPs by
      ActR-IIs has been analyzed structurally and functionally, but no detailed
      analysis of BMPR-II has been reported. The objective of this study was to
      determine ligand-binding epitopes and specificity determinants in two regions,
      the hydrophobic patch and the A-loop of the BMPR-II extracellular domain (ECD). A
      series of alanine-substituted variants was generated using a recently published X
      ray structure of the unliganded form of the ovine BMPR-II ECD as a guide. These
      variants were characterized using one-dimensional NMR and functional activity
      assays with BMP-2, BMP-7 and GDF-5 as ligands. The results showed that alanine
      substitutions of conserved residues W85 and Y113 within the hydrophobic patch of
      the ECD differentially perturbed BMP ligand binding without disrupting receptor
      folding, suggesting that they are critical determinants for ligand binding and
      ligand specificity. Our results further revealed that the nonconserved residue
      L69 in the hydrophobic patch contributes to ligand-binding activity and
      specificity. Mutations of several residues within the A-loop resulted in minimal
      effects on the binding of the different BMP ligands. Overall, these observations
      identify several amino acid residues that play different roles in BMPR-II and
      ActR-II and thereby enable BMPR-II and ActR-IIs to bind different subclasses of
      BMP ligands.

PMID- 18342888
TI  - Blunted ACTH response to dexamethasone suppression-CRH stimulation in
      posttraumatic stress disorder.
AB  - Previous studies have suggested that patients with posttraumatic stress disorder
      (PTSD) have an enhanced negative feedback sensitivity of the hypothalamic
      pituitary-adrenal (HPA) system and a blunted ACTH response to corticotropin
      releasing hormone (CRH). The effects of two dexamethasone dosages (0.75 and 1.5
      mg) on the ACTH and cortisol concentrations after CRH stimulation (100 microg)
      were studied in eight patients with PTSD and matched healthy control subjects.
      Compared to healthy subjects, patients with PTSD have a blunted ACTH response to
      CRH. Cortisol concentrations were only significantly influenced by dexamethasone
      dosage. Our results give further evidence for a central role of the pituitary in
      reflecting changes of the negative feedback sensitivity of the HPA system in
      patients with PTSD.

PMID- 18342890
TI  - Mutual interaction in network motifs robustly sharpens gene expression in
      developmental processes.
AB  - The gene regulatory network of a developmental process contains many mutually
      repressive interactions between two genes. They are often regulated by or
      regulate an additional factor, which constitute prominent network motifs, called
      regulated and regulating mutual loops. Our database analysis on the gene
      regulatory network for Drosophila melanogaster indicates that those with mutual
      repression are working specifically for the segmentation process. To clarify
      their biological roles, we mathematically study the response of the regulated
      mutual loop with mutual repression to input stimuli. We show that the mutual
      repression increases the response sensitivity without affecting the threshold
      input level to activate the target gene expression, as long as the network output
      is unique for a given input level. This high sensitivity of the motif can
      contribute to sharpening the spatial domain pattern without changing its
      position, assuring a robust developmental process. We also study transient
      dynamics that shows shift of domain boundary, agreeing with experimental
      observations. Importance of mutual repression is addressed by comparing with
      other types of regulations.

PMID- 18342891
TI  - The influence of social structure on the propagation of social information in
      artificial primate groups: a graph-based simulation approach.
AB  - Observations of primate groups have shown that social learning can lead to the
      development of temporal stable traditions or even proto-culture. The social
      structure of primate groups is highly diverse and it has been proposed that
      differences in the group structure shall influence the patterns of social
      information transmission. While empirical studies have mainly focused on the
      psychological mechanisms of social learning in individuals, the phenomenon of
      information propagation within the group has received relatively little
      attention. This might be due to the fact that formal theories that allow actual
      testing have not been formulated, or were kept too simple, ignoring the social
      dynamics of multi-agent societies. We want to propose a network approach to
      social information transmission that (1) preserves the complexity of the social
      structure of primate groups and (2) allows direct application to empirical data.
      Results from simulation experiments with artificial group structures confirm that
      association patterns of group-members influence the expected speed of information
      transmission during the propagation process. Introducing a forgetting rate shows
      that under certain conditions the proportion of informed individuals will reach a
      stable rate in some systems while it will drop to zero in others. This suggests
      that the likelihood to observe temporal stable traditions shall differ between
      social systems with different structure.

PMID- 18342892
TI  - Beneficial effects of diclofenac therapy on serum lipids, oxidized low-density
      lipoprotein and antioxidant defenses in rats.
AB  - To study the effects of diclofenac, a nonselective nonsteroidal anti-inflammatory
      drug (NSAID), on lipid profile, oxidized low-density-lipoprotein (Ox-LDL), serum
      antioxidant defenses and markers of oxidative stress, male Wistar rats were
      divided into two groups (n=10): (C) receiving intramuscularly a single daily dose
      of saline (NaCl 0.9%), and (AI) receiving intramuscularly a single daily dose of
      10 mg/kg diclofenac sodium (C14H10Cl2NNaO2). After 28 days diclofenac-treated
      rats had lower Ox-LDL, apoprotein B (apo-B), apo-B/LDL-cholesterol and lipid
      hydroperoxide than C. Total antioxidant substances and superoxide dismutase were
      increased in diclofenac-treated rats, while no significant changes were observed
      in catalase, glutathione peroxidase and nitric oxide. A perincubation test done
      to examine the possibility of mechanism-based activation showed that diclofenac
      had no effect on maximal superoxide dismutase velocity, but significantly reduced
      the Michaelis-Menten (KM) constant, indicating that diclofenac induced SOD
      activation increasing substrate linkage affinity to the enzyme-catalytic site. In
      conclusion, diclofenac had beneficial effects decreasing Ox-LDL and improving
      antioxidant defense. It appears that the application of this agent may be
      feasible and beneficial for serum antioxidant protection, which certainly would
      bring new insights on dyslipidemia control.

PMID- 18342893
TI  - Visualization of spatial patterns and temporal trends for aerial surveillance of
      illegal oil discharges in western Canadian marine waters.
AB  - This paper examines the use of exploratory spatial analysis for identifying
      hotspots of shipping-based oil pollution in the Pacific Region of Canada's
      Exclusive Economic Zone. It makes use of data collected from fiscal years
      1997/1998 to 2005/2006 by the National Aerial Surveillance Program, the primary
      tool for monitoring and enforcing the provisions imposed by MARPOL 73/78. First,
      we present oil spill data as points in a "dot map" relative to coastlines,
      harbors and the aerial surveillance distribution. Then, we explore the intensity
      of oil spill events using the Quadrat Count method, and the Kernel Density
      Estimation methods with both fixed and adaptive bandwidths. We found that oil
      spill hotspots where more clearly defined using Kernel Density Estimation with an
      adaptive bandwidth, probably because of the "clustered" distribution of oil spill
      occurrences. Finally, we discuss the importance of standardizing oil spill data
      by controlling for surveillance effort to provide a better understanding of the
      distribution of illegal oil spills, and how these results can ultimately benefit
      a monitoring program.

PMID- 18342894
TI  - An effective transplanting technique using shells for restoration of Zostera
      marina habitats.
AB  - Significant declines in seagrass coverage have occurred in many parts of the
      world. In recent decades, transplanting projects for seagrass restoration at die
      off areas have been attempted, but most current seagrass transplanting techniques
      are cost and labor intensive. We have developed a new seagrass transplanting
      method in which oyster shells are used as an anchoring device, and does not
      require SCUBA diving for sub-tidal planting. Here, we tested the shell method for
      feasibility and efficiency in large-scale seagrass restoration. Planting units
      consisting of two Zostera marina shoots anchored to one oyster shell were dropped
      from a boat to settle on the sediment at the test site. Four transplanting trials
      were conducted throughout the experimental period (December 2003, January,
      February, and November 2004) in Koje Bay on the southern coast of Korea. Eelgrass
      shoots planted using the shell method successfully established at the test areas,
      and the survival rates of transplants were comparable to those obtained using
      other common planting techniques. The transplant shoot density declined during
      the first 2-3 months following transplantation due to the initial transplant
      shock, and then surviving shoots became established at the sites and produced new
      lateral shoots after these periods. Plant size and leaf productivity of
      transplants 7 months post-transplanting were similar to or exceeded those of pre
      existed shoots, suggesting that the physiological status of transplants is
      similar to that of natural population after 7 months. Because the shell method
      did not require workers to be in the water, the method was cost and labor
      effective. Additionally, given that shells originate from marine environments,
      the shell method did not leave any hazardous materials in the transplanting areas
      after restoration.

PMID- 18342895
TI  - First experiments on the maternal transfer of metals in the cuttlefish Sepia
      officinalis.
AB  - The aim of this study was to provide a first insight on the incorporation of
      eight metals in the eggs of the cuttlefish Sepia officinalis via maternal
      transfer, using radiotracer techniques ((110m)Ag, (241)Am, (109)Cd, (60)Co,
      (134)Cs, (54)Mn, (75)Se and (65)Zn). The cuttlefish was fed daily with
      radiolabelled crabs for two weeks; it then started to spawn every three days.
      Among the eight tracers, only (110m)Ag, (75)Se and (65)Zn were significantly
      transferred to the eggs. The radiotracer distribution among the egg compartments
      showed that (75)Se and (65)Zn were accumulated mainly in the vitellus whereas
      (110m)Ag was found in similar proportion in the vitellus and the eggshell. During
      the embryonic development, (75)Se and (65)Zn contained in the vitellus were
      progressively transferred to the embryo, likely to supply its metabolic needs in
      these essential elements. Although it has no known biological functions, Ag
      contained in both vitellus and eggshell was also transferred to the embryo.
      Overall, our results showed that transfer of Ag, Se, and Zn does actually occur
      from a female cuttlefish to its eggs, at least during the last two weeks before
      spawning.

PMID- 18342896
TI  - Calculating the time to extinction of a reactivating virus, in particular bovine
      herpes virus.
AB  - The expected time to extinction of a herpes virus is calculated from a rather
      simple population-dynamical model that incorporates transmission, reactivation
      and fade-out of the infectious agent. We also derive the second and higher
      moments of the distribution of the time to extinction. These quantities help to
      assess the possibilities to eradicate a reactivating infection. The key
      assumption underlying our calculations is that epidemic outbreaks are fast
      relative to the time scale of demographic turnover. Four parameters influence the
      expected time to extinction: the reproduction ratio, the reactivation rate, the
      population size, and the demographic turn-over in the host population. We find
      that the expected time till extinction is very long when the reactivation rate is
      high (reactivation is expected more than once in a life time). Furthermore, the
      infectious agent will go extinct much more quickly in small populations. This
      method is applied to bovine herpes virus (BHV) in a cattle herd. The results
      indicate that without vaccination, BHV will persist in large herds. The use of a
      good vaccine can induce eradication of the infection from a herd within a few
      decades. Additional measures are needed to eradicate the virus from a whole
      region within a similar time-span.

PMID- 18342897
TI  - Type 2 diabetes mellitus and skeletal muscle metabolic function.
AB  - Type 2 diabetic patients are characterized by a decreased fat oxidative capacity
      and high levels of circulating free fatty acids (FFAs). The latter is known to
      cause insulin resistance, in particularly in skeletal muscle, by reducing insulin
      stimulated glucose uptake, most likely via accumulation of lipid inside the
      muscle cell. A reduced skeletal muscle oxidative capacity can exaggerate this.
      Furthermore, type 2 diabetes is associated with impaired metabolic flexibility,
      i.e. an impaired switching from fatty acid to glucose oxidation in response to
      insulin. Thus, a reduced fat oxidative capacity and metabolic inflexibility are
      important components of skeletal muscle insulin resistance. The cause of these
      derangements in skeletal muscle of type 2 diabetic patients remains to be
      elucidated. An impaired mitochondrial function is a likely candidate. Evidence
      from both in vivo and ex vivo studies supports the idea that an impaired skeletal
      muscle mitochondrial function is related to the development of insulin resistance
      and type 2 diabetes mellitus. A decreased mitochondrial oxidative capacity in
      skeletal muscle was revealed in diabetic patients, using in vivo 31-Phosphorus
      Magnetic Resonance Spectroscopy (31P-MRS). However, quantification of
      mitochondrial function using ex vivo high-resolution respirometry revealed
      opposite results. Future (human) studies should challenge this concept of
      impaired mitochondrial function underlying metabolic defects and prove if
      mitochondria are truly functional impaired in insulin resistance, or low in
      number, and whether it represents the primary starting point of pathogenesis of
      insulin resistance, or is just an other feature of the insulin resistant state.

PMID- 18342898
TI  - The enhancement of arbovirus transmission and disease by mosquito saliva is
      associated with modulation of the host immune response.
AB  - Arthropod-borne (arbo-) viruses have emerged as a major human health concern.
      Viruses transmitted by mosquitoes are the cause of the most serious and
      widespread arbovirus diseases worldwide and are ubiquitous in both feral and
      urban settings. Arboviruses, including dengue and West Nile virus, are injected
      into vertebrates within mosquito saliva during mosquito feeding. Mosquito saliva
      contains anti-haemostatic, anti-inflammatory and immunomodulatory molecules that
      facilitate the acquisition of a blood meal. Collectively, studies investigating
      the effects of mosquito saliva on the vertebrate immune response suggest that at
      high concentrations salivary proteins are immmunosuppressive, whereas lower
      concentrations modulate the immune response; specifically, T(H)1 and antiviral
      cytokines are downregulated, while T(H)2 cytokines are unaffected or amplified.
      As a consequence, mosquito saliva can impair the antiviral immune response, thus
      affecting viral infectiousness and host survival. Mounting evidence suggests that
      this is a mechanism whereby arbovirus pathogenicity is enhanced. In a range of
      disease models, including various hosts, mosquito species and arthropod-borne
      viruses, mosquito saliva and/or feeding is associated with a potentiation of
      virus infection. Compared with arbovirus infection initiated in the absence of
      the mosquito or its saliva, infection via mosquito saliva leads to an increase in
      virus transmission, host susceptibility, viraemia, disease progression and
      mortality.

PMID- 18342899
TI  - Sex-steroid hormones and EGF signalling in breast and prostate cancer cells:
      targeting the association of Src with steroid receptors.
AB  - Sex-steroid hormones trigger association of their receptors with signalling
      effectors. Remarkably, various hormonal effects, such as DNA synthesis of
      different cell types are evoked by this association. In mammary and prostate
      cancer cells, EGF, androgen or estradiol trigger the assembly of AR/ER/Src
      complex. SH2-Src interacts with a phosphotyrosine residue of ER and SH3-Src
      interacts with a proline rich sequence of AR. This association stimulates Src
      dependent signalling, DNA synthesis and cytoskeleton changes. We now report that
      in prostate or breast cancer cells stimulated by EGF or androgen or estradiol,
      small peptides (6-10 amino acids) derived from ER or AR sequences involved in the
      receptor interaction with Src, prevent AR/ER/Src association, Src/Erk pathway
      stimulation, cyclin D1 expression and DNA synthesis. The peptide action is
      restricted to cells expressing the steroid receptors and to signals mediated by
      these receptors. Remarkably, the peptides do not modify the steroid receptor
      dependent transcriptional activity. Growth of prostate or mammary cancer cell
      xenografts is strongly inhibited by these novel receptor antagonists.

PMID- 18342900
TI  - EPR studies of in vivo radical production by 3,3',5,5'-tetrabromobisphenol A
      (TBBPA) in the Sprague-Dawley rat.
AB  - Brominated flame retardants (BFRs) are present in many consumer products ranging
      from fabrics to plastics and electronics. Wide use of flame retardants can pose
      an environmental hazard and it is of interest to determine the mechanism of their
      toxicity. Of all the BFRs, 3,3',5,5'-tetrabromobisphenol A (TBBPA) is produced in
      the largest volume. Previous studies by Szymanska et al. (2000) have shown that
      TBBPA is hepatotoxic in rats. We report here that when TBBPA (100 or 600 mg/kg)
      dissolved in DMSO and alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (POBN) was
      administered ip to male Sprague-Dawley rats the POBN/CH(3) spin adduct was
      detected by electron paramagnetic resonance (EPR) in the bile. When (13)C-DMSO
      was employed the POBN/C(13)H(3) adduct was observed. Also present in the bile was
      the 2,6-dibromobenzosemiquinone radical derived from 2,6-dibromohydroquinone, a
      known metabolite of TBBPA. Reaction of the 2,6-dibromobenzosemiquinone radical
      with oxygen would generate superoxide from which hydrogen peroxide can form by
      dismutation. The hydroxyl radical generated via the Fenton reaction from hydrogen
      peroxide reacts in vivo with DMSO to give the methyl radical which is trapped by
      POBN. These observations suggest that the hepatotoxicity of TBBPA in rats may be
      due to the in vivo generation of the hydroxyl radical as a result of redox
      reactions involving the TBBPA metabolite 2,6-dibromohydroquinone and its
      corresponding semiquinone radical.

PMID- 18342901
TI  - Revisiting cangitoxin, a sea anemone peptide: purification and characterization
      of cangitoxins II and III from the venom of Bunodosoma cangicum.
AB  - Sodium channel toxins from sea anemones are employed as tools for dissecting the
      biophysical properties of inactivation in voltage-gated sodium channels.
      Cangitoxin (CGTX) is a peptide containing 48 amino acid residues and was formerly
      purified from Bunodosoma cangicum. Nevertheless, previous works reporting the
      isolation procedures for such peptide from B. cangicum secretions are
      controversial and may lead to incorrect information. In this paper, we report a
      simple and rapid procedure, consisting of two chromatographic steps, in order to
      obtain a CGTX analog directly from sea anemone venom. We also report a
      substitution of N16D in this peptide sample and the co-elution of an inseparable
      minor isoform presenting the R14H substitution. Peptides are named as CGTX-II and
      CGTX-III, and their effects over Nav1.1 channels in patch clamp experiments are
      demonstrated.

PMID- 18342902
TI  - Disturbance of smooth muscle regulatory function by Eisenia foetida toxin
      lysenin: insight into the mechanism of smooth muscle contraction.
AB  - Lysenin, a toxin present in the coelomic fluid of the earthworm Eisenia foetida,
      is known to cause a long-lasting contraction of rat aorta smooth muscle strips.
      We addressed the mechanisms underlying its action on smooth muscle cells and
      present the first report demonstrating a completely new property of lysenin
      unrelated to its basic sphingomyelin-binding ability. Here we report lysenin
      enhancement effect on smooth muscle actomyosin ATPase activity and the ability of
      networking the actin filaments. The maximum enhancement of the ATPase activity of
      actomyosin at 120 mM KCl was observed at a molar ratio of lysenin to actin of
      about 1:10(5), while at 70 mM KCl at the ratio of about 1:10(6). The effect of
      lysenin became most pronounced only when both smooth muscle regulatory proteins,
      tropomyosin and caldesmon, were present. Co-sedimentation experiments indicated
      that lysenin did not displace neither tropomyosin nor caldesmon from the thin
      filament. Thus, the lysenin-dependent abolishment of the inhibitory effect of
      caldesmon on the ATPase activity was related rather to the modification of the
      filament structure. The ability of the toxin to exert its stimulatory effect at
      extremely low concentrations (as low as one molecule of lysenin per 10(6) actin
      molecules) may result from the long-range cooperative transitions in the entire
      thin filament with an involvement of smooth muscle tropomyosin, while the role of
      caldesmon may be limited exclusively to the inhibition of ATPase activity.

PMID- 18342903
TI  - Immunochemical and proteomic technologies as tools for unravelling toxins
      involved in envenoming by accidental contact with Lonomia obliqua caterpillars.
AB  - The accidental contact with Lonomia obliqua caterpillar causes local and systemic
      symptoms (such as fibrinogen depletion), leading, in some cases, to serious
      clinical complications (acute renal failure and intracranial haemorrhage).
      Fortunately, a successful therapeutical approach using anti-Lonomic serum,
      produced in horses against L. obliqua's bristle extract, has already been put in
      place. However, a global view of immunogenic toxins involved in the coagulation
      disorders could help to elucidate the envenoming process. In the present study,
      our aim was to identify bristle extract's immunogenic components, especially
      those related to the haemostasis, coupling proteomics and immunochemical
      approaches (bidimensional electrophoresis, mass spectrometry and immunoblotting).
      The bidimensional map of bristle extract showed a broad profile of 157 silver
      stained spots, where at least 153 spots were immunochemically revealed. Twenty
      four of these spots were submitted to sequencing by mass spectrometry and three
      different categories of proteins were identified: lipocalins, cuticle proteins
      and serpins. From these protein families, it was observed that the most abundant
      was the lipocalin family, specifically represented by different isoforms of Lopap
      (a prothrombin activator protein), reinforcing its relevance during envenoming.
      Peptide sequences of several other immunochemically revealed spots showed no
      correspondence to any known sequence and were classified as unknown proteins.
      These proteins could represent new immunogenic molecules and/or toxins. The
      sequences presented in this article can be used for oligonucleotide design aiming
      the amplification of cDNAs coding for new molecules using L. obliqua bristles'
      cDNA libraries or isolated RNAs as template.

PMID- 18342904
TI  - Role of endocytosis and cathepsin-mediated activation in Nipah virus entry.
AB  - The recent discovery that the Nipah virus (NiV) fusion protein (F) is activated
      by endosomal cathepsin L raised the question if NiV utilize pH- and protease
      dependent mechanisms of entry. We show here that the NiV receptor ephrin B2,
      virus-like particles and infectious NiV are internalized from the cell surface.
      However, endocytosis, acidic pH and cathepsin-mediated cleavage are not necessary
      for the initiation of infection of new host cells. Our data clearly demonstrate
      that proteolytic activation of the NiV F protein is required before incorporation
      into budding virions but not after virus entry.

PMID- 18342905
TI  - Ozonation kinetics of cork-processing water in a bubble column reactor.
AB  - The oxidative degradation of organic pollutants present in cork-processing water
      at natural pH (6.45) was studied in a bubble column ozonation reactor. A steady
      reduction in both chemical oxygen demand (COD) and total organic carbon (TOC) was
      observed under the action of ozone alone and the feasibility of deep
      mineralisation (organic matter removal more than 90% in 120 min under the
      following experimental conditions: liquid volume 9L; superficial gas velocity
      6.8x10(-3) m s(-1); ozone partial pressure 1.31 kPa; initial COD 328 mg L(-1);
      initial TOC 127 mg L(-1)) was demonstrated. The monitoring of pH, redox potential
      (ORP) and the mean oxidation number of carbon (MOC) was correlated with the
      oxidation and mineralisation of the organic species in the water. The ozonation
      of cork-processing water in the bubble column was analysed in terms of a mole
      balance coupled with ozonation kinetics modelled by the two-film theory of mass
      transfer and chemical reaction. Under the experimental conditions used, and in
      contrast with the literature, it was determined that the reaction follows a fast
      kinetic regime at the beginning of the oxidation process, shifting to the
      moderate and the slow kinetic regimes at later stages of the oxidation reaction.
      The dynamic change of the rate coefficient estimated by the model was correlated
      to changes in the water composition.

PMID- 18342906
TI  - The mineralization of 5-amino-2,4,6-triiodoisophthalic acid by a two-stage fixed
      bed reactor.
AB  - Iodinated X-ray contrast media have been detected in hospital effluent, sewage
      treatment plant effluent, rivers and groundwater aquifers. No process has been
      developed to remove triiodinated aromatic molecules. In this paper, we present a
      biological sequential process using an anaerobic fixed-bed reactor coupled in
      series with an aerobic fixed-bed reactor for degrading 5-amino-2,4,6
      triiodoisophthalic acid (ATIA), the core structure of a X-ray contrast media
      family. The results obtained showed that the coupled reactor eliminated up to
      870+/-44 mg of carbon L(-1) day(-1), with a molar ethanol/ATIA ratio of 4 in the
      feeding medium. The anaerobic reactor (ANR) undertook the majority of the
      deiodination of the aromatic nucleus and had a maximum deiodination rate of
      23.4+/-0.06 mM day(-1). The aerobic reactor (AER) mineralized ATIA and was also
      able to eliminate its metabolites. This study suggests that the mineralization of
      ATIA can be achieved efficiently in a coupled anaerobic-aerobic bioreactor.

PMID- 18342907
TI  - High-performance thin-layer hydrogel composite membranes for ultrafiltration of
      natural organic matter.
AB  - Thin-layer hydrogel composite (TLHC) ultrafiltration (UF) membranes were
      synthesized by photo-grafting of either poly(ethylene glycol) methacrylate
      (PEGMA) or N,N-dimethyl-N-(2-methacryloyloxyethyl-N-(3-sulfopropyl) ammonium
      betaine (SPE) onto commercial polyethersulfone (PES) UF membranes. The
      performance of TLHC UF membranes was evaluated for natural organic matter (NOM)
      filtration and compared to commercial PES UF membranes. The fouling evaluation
      was done by investigation of membrane-solute interactions (adsorptive fouling)
      and membrane-solute-solute interactions (UF). The results suggest that the TLHC
      membranes convincingly displayed a higher adsorptive fouling resistance than
      unmodified PES UF membranes. In long-term stirred dead-end UF, a much lower
      fouling was observed for TLHC membranes than for commercial membranes with the
      same flux and rejection. Further, water flux recovery was also much higher. An
      analysis using an existing blocking model was performed in order to elucidate the
      effect of a polymer hydrogel layer on fouling mechanism as well as cake layer
      characteristics. The TLHC membranes synthesized by photo-grafting of PEGMA (40
      g/L) and PEGMA with a low concentration of cross-linker monomer in the reaction
      mixture (ratio: 40/0.4 (g/L)/(g/L)) showed a much better performance than the
      other composite membranes. Those membranes could reduce the cake resistance on
      the membrane surface. This work has relevance for the design of high-performance
      UF membranes for applications in water treatment.

PMID- 18342908
TI  - Phosphatase activity in anaerobic bioreactors for wastewater treatment.
AB  - Phosphatase (PO4ase) activity was investigated in continuous and fed-batch
      anaerobic bioreactors for wastewater treatment. PO4ase levels were high in
      continuously fed reactors (880-2632 micromol/L/h), compared to a fed-batch
      reactor (FBR) (540-1249 micromol/L/h). Alkaline and acid PO4ases were present in
      all the reactors, but in varying magnitudes and total PO4ase activity exhibited a
      10-30% variation even at steady-state reactor conditions. The PO4ase activity was
      not affected by the inorganic phosphate (Pi) level in the reactors, but biomass
      level and wastewater type, including specific PO4ases (either alkaline or acid),
      strongly influenced the PO4ase activity in a reactor. Both flocculated and
      suspended cells produced PO4ase, and 60-65% of the enzyme was cell bound,
      remaining entrapped in the extracellular matrix and in cell-free form. Batch
      studies with anaerobic sludge showed a negative correlation between Pi and PO4ase
      activity. An increase in PO4ase activity was observed under starvation and higher
      salinity (above 15 g/L). Glucose and propionate (at 10 mM level) induced PO4ase
      activity, whereas acetate and butyrate (10 mM) addition had no response. This
      study also reveals that Archaea and bacteria contributed 45% and 55%,
      respectively, of total PO4ase activity in anaerobic sludge.

PMID- 18342909
TI  - A time series model for influent temperature estimation: application to dynamic
      temperature modelling of an aerated lagoon.
AB  - Thirty-nine linear regression and time series models were built and calibrated
      for influent temperature (Ti) estimation at the primary aerated facultative
      lagoon in a municipal wastewater treatment plant. The models were based on mean
      daily ambient air temperature (Ta) and/or daily rainfall (P), and-optionally
      wastewater temperature autoregression. The best fits were achieved with some time
      series models involving Ta and P, and Ti autoregression. The best-fit model was
      able to estimate influent temperature with a root-mean-square-error of 0.5
      degrees C, and an R2 of 0.925, for the calibration period of 10.5 months. In
      addition, a dynamic lagoon-temperature (Tw) model from the literature was
      modified in its terms of solar radiation and aeration latent heat, and applied to
      the primary lagoon. The model was fed with the estimated influent temperature,
      and five model parameters were identified by calibration against 10.5-month Tw
      data. Dynamic lagoon-temperature estimation results were comparable to or better
      than other results of long-term simulations found in the literature. Sensitivity
      analyses were run on both models. Further validation with independent sets of
      data is needed for verification of the predictive capability of the models.

PMID- 18342910
TI  - Mercury in air in an area impacted by strong industrial activities.
AB  - The concentrations of total gaseous mercury (TGM) and its relevant environmental
      parameters were measured at a highly industrialized area in the Ban Wall
      industrial complex (BWIC) in An San city, Korea from March to May 2005. The mean
      concentrations of Hg measured during the entire study period were computed to be
      6.32+/-8.56 ng m(-3) (range of 2.32-181 ng m(-3); N=1,160). Due to the effects of
      strong man-made activities, the significantly high Hg concentration levels (e.g.,
      at or above 10 ng m(-3)) comprised about 7.5% of all data with the mean of 21.8+/
      26.3 ng m(-3) (N=87). By separating the data into daytime and nighttime periods,
      the Hg values exhibited a notable daytime enhancement possibly due to strong man
      made activities during working hours. The results of the correlation analysis
      indicated the possible relationship between the Hg concentration and the
      temperature as well as several pollutant species (e.g., NO(2) and NO(x)).
      Evaluation of the Hg data in relation with the air mass transport pattern
      confirms that the Hg concentration levels in this industrial area are affected
      most eminently by local, rather than distant, pollution sources.

PMID- 18342911
TI  - Trichoderma atroviride F6 improves phytoextraction efficiency of mustard
      (Brassica juncea (L.) Coss. var. foliosa Bailey) in Cd, Ni contaminated soils.
AB  - Trichoderma atroviride F6, isolated from decaying feather and resistant to 100 mg
      l(-1) Cd2+ and 250 mg l(-1) Ni2+, was applied for rhizoremediation of Cd, Ni and
      Cd-Ni combination contaminated soils through association with Brassica juncea
      (L.) Coss. var. foliosa. The strain significantly alleviated the cellular
      toxicity of cadmium and nickel to plants. Inoculation of B. juncea (L.) Coss.
      var. foliosa with T. atroviride F6 resulted a 110%, 40% and 170% increase in
      fresh weight in Cd, Ni and Cd-Ni contaminated soils, respectively (P<0.05). The
      translocation factors and metal bioconcentration factors calculated for the
      inoculated plant were increased compared to the noninoculated plants. The results
      indicated that the efficiency of phytoextraction for B. juncea (L.) Coss. var.
      foliosa enhanced after inoculating with T. atroviride F6. The fungal treated
      plants grown in Cd-Ni combination contaminated soils showed higher
      phytoextraction efficiency than those in Cd or Ni contaminated soils. Thus, it is
      suggested that the fungus T. atroviride F6 endowed with organic-degrading
      capabilities could be exploited for fungi-assisted phytoremediation of mixed
      organic-metal contaminated soils.

PMID- 18342912
TI  - Reaction pathways of dimethyl phthalate degradation in TiO2-UV-O2 and TiO2-UV
      Fe(VI) systems.
AB  - The photocatalytic degradation of dimethyl phthalate (DMP) in aqueous TiO2
      suspension under UV illumination has been investigated using oxygen (O2) and
      ferrate (Fe(VI)) as electron acceptors. The experiments demonstrated that Fe(VI)
      was a more effective electron acceptor than O2 for scavenging the conduction band
      electrons from the surface of the catalyst. Some major intermediate products from
      DMP degradation were identified by HPLC and GC/MS analyses. The analytical
      results identified dimethyl 3-hydroxyphthalate and dimethyl 2-hydroxyphthalate as
      the two main intermediate products from the DMP degradation in the TiO2-UV-O2
      system, while in contrast phthalic acid was found to be the main intermediate
      product in the TiO2-UV-Fe(VI) system. These findings indicate that DMP
      degradation in the TiO2-UV-O2 and TiO2-UV-Fe(VI) systems followed different
      reaction pathways. An electron spin resonance analysis confirmed that hydroxyl
      radicals existed in the TiO2-UV-O2 reaction system and an unknown radical species
      (most likely an iron-oxo species) is suspected to exist in the TiO2-UV-Fe(VI)
      reaction system. Two pathway schemes of DMP degradation in the TiO2-UV-O2 and
      TiO2-UV-Fe(VI) reaction systems are proposed. It is believed that the radicals
      formed in the TiO2-UV-O2 reaction system preferably attack the aromatic ring of
      the DMP, while in contrast the radicals formed in the TiO2-UV-Fe(VI) reaction
      systems attack the alkyl chain of DMP.

PMID- 18342913
TI  - Phytostabilization of copper mine tailings with biosolids: implications for metal
      uptake and productivity of Lolium perenne.
AB  - A greenhouse pot experiment was conducted to evaluate the feasibility of using
      biosolids and Lolium perenne for the phytostabilization of copper mine tailings
      and to evaluate the patterns of metal accumulation and translocation in plants.
      Biosolids were applied either on the surface or mixed with the tailings at rates
      of 0, 6, and 12% w/w. All pots were seeded with L. perenne and after six months,
      the plants were harvested and separated into roots and shoots for metal
      concentrations analyses as well as some physiological characteristics of the
      plants. In order to correlate the metal content in plant tissues with some
      chemical properties, the pore-water of the substrates was analyzed for metals, pH
      and dissolved organic carbon. Results showed that biosolids application increased
      the dry biomass production of L. perenne and the shoot concentrations of N and
      chlorophyll. On the other hand, biosolids increased the concentration of Cu and
      Zn in the pore-water and in plant tissues. Despite this, there were no evident
      symptoms of phytotoxicity and the concentration of metals was within the normal
      ranges described for plants and below the maximum tolerable level for animals. In
      addition, plant tissue analysis showed that the application of biosolids could
      significantly reduce Mo uptake and shoot accumulation in plants. The metals were
      taken up by plants in the following order: Cu>Zn>Mo>Cd. The distribution patterns
      of metals in plants showed that metals were mainly accumulated in the roots and
      only a small amount of them were transported to the shoots. These results suggest
      that mixed application of biosolids (6%) and the use of L. perenne could be
      appropriate for use in programs of phytostabilization of copper mine tailings.
      However, these results should be tested under field conditions in order to
      confirm their efficacy under semi-arid Mediterranean climate conditions.

PMID- 18342914
TI  - Tracing the sources of nitrate in the Han River watershed in Korea, using
      delta15N-NO3- and delta18O-NO3- values.
AB  - The dissolved nitrate concentrations and their nitrogen and oxygen isotopic
      ratios were analyzed in seasonal samples from Korea's Han River to ascertain the
      seasonal and spatial variations of dissolved nitrate and its possible sources.
      Nitrate concentrations in the South Han River (SHR) were much higher than those
      in the North Han River (NHR), probably because of the more extensive distribution
      of agricultural fields, residential areas and animal farms in the SHR drainage
      basin. The nitrogen isotopic composition of dissolved nitrate indicates that
      nitrate-nitrogen (NO(3)(-)-N) is derived mainly from atmospheric deposition
      and/or soil organic matter in the NHR but comes principally from manure or
      sewage, with only a minor contribution from atmospheric deposition or soil
      organic matter, in the SHR. The oxygen isotopic compositions of dissolved nitrate
      suggest that most atmospheric nitrate undergoes microbial nitrification before
      entering the river.

PMID- 18342915
TI  - Correlation between factors involved in the local haemostasis and angiogenesis in
      full term human placenta.
AB  - INTRODUCTION: Few studies have been carried out to investigate whether distinct
      areas of full term placenta express different amounts of markers involved in the
      placental haemostasis and angiogenesis. A possible relationship between the
      expression of genes involved in the haemostasis and angiogenesis of human
      placenta has not been investigated. MATERIALS AND METHODS: Twenty-eight fresh
      human placentas (35-41 weeks of gestation) from uneventful pregnancies were
      dissected with two different methods. Quantitative mRNA expression of the tissue
      factor (TF), TF pathway inhibitor (TFPI), TFPI-2, plasminogen activator inhibitor
      (PAI-2), annexin V (Anx V), vascular endothelial growth factor (VEGF), and
      thrombomodulin (TM) genes was evaluated by quantitative real time PCR system.
      Histology of each sample was graded. RESULTS: Gene expression of all the
      considered markers was not significantly different in each area, using both the
      different methods of dissection. A significant correlation (p<0.05) was found
      between the expression of TF and TFPI-2. TF and TFPI-2 were significantly
      (p<0.05) associated with VEGF, whereas a stronger association (p<0.01) was found
      between TFPI and TFPI-2. TFPI and TFPI-2 were strongly associated with PAI-2
      expression (p<0.01). CONCLUSIONS: In placentas with central cord insertion, gene
      expression is not dependent on the method of sampling site. A significant
      relationship between haemostasis and angiogenesis in at term placentas was shown.

PMID- 18342916
TI  - Delayed orchiectomy at postchemotherapy retroperitoneal lymph node dissection due
      to laterality of retroperitoneal metastatic pattern consistent with testicular
      primary: assessment of pathologic findings.
AB  - OBJECTIVES: It has been estimated that extragonadal germ cell tumors (EGCTs)
      constitute 3% to 5% of germ cell neoplasms. An interesting clinical scenario
      occurs when a patient with a presumed EGCT and normal testicular examination and
      ultrasound findings has a retroperitoneal metastatic pattern consistent with
      either a right or left-sided testicular primary. We reviewed the pathologic data
      of patients presenting with these clinical findings after delayed orchiectomy at
      postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). METHODS: We
      identified 14 patients with apparent EGCT who had undergone simultaneous
      orchiectomy at PC-RPLND at our institution from July 1979 to July 2002 because of
      a lateralizing pattern of retroperitoneal metastases concerning for a testicular
      primary. Of the 14 patients, 3 had completely normal testicular ultrasound
      findings after chemotherapy and 11 had minimal ultrasound findings not consistent
      with a testicular tumor. RESULTS: Two (14%) of the PC orchiectomy specimens
      contained mature teratoma and eight (57%) contained necrosis and/or focal
      fibrosis. Thus, 10 (71%) of 14 patients undergoing PC orchiectomy at PC-RPLND
      because of metastatic disease laterality had evidence of a testicular primary.
      CONCLUSIONS: Most (71%) patients with a presumed EGCT who underwent PC
      orchiectomy because of lateralizing retroperitoneal metastases had histologic
      evidence of a testicular primary (20% teratoma, 80% focal necrosis or fibrosis).
      If the retroperitoneal pattern of metastatic tumor spread is consistent with a
      primary testicular tumor, we offer PC orchiectomy to patients with apparent EGCT
      at PC-RPLND, even if the PC testicular examination and ultrasound findings are
      normal.

PMID- 18342917
TI  - Impact of comorbidity on survival of Danish prostate cancer patients, 1995-2006:
      a population-based cohort study.
AB  - OBJECTIVES: The existence of comorbid diseases among men with newly diagnosed
      prostate cancer may affect prostate cancer prognosis. METHODS: We identified
      patients (n = 8114) with a first-time discharge diagnosis of prostate cancer from
      Danish hospitals between 1995 and 2006. We measured comorbidity using the
      Charlson Comorbidity Index. RESULTS: The number of patients doubled between 1995
      and 2006. The proportion of patients with Charlson scores of 0 (no comorbidity)
      increased from 62% to 63% of total patients diagnosed, whereas the proportion of
      patients with Charlson scores of 1 to 2 (moderate comorbidity) decreased from 31%
      to 29%, and the proportion with Charlson scores of 3 or higher (severe
      comorbidity) increased from 106 to 227 (7% to 8%). Among patients with a Charlson
      score of 0, the 1-year survival rate improved from 79% to 94%; among patients
      with Charlson scores of 1 to 2, the 1-year survival rate increased from 68% to
      83%; and in patients with a Charlson score of 3 or higher, this rate increased
      from 61% to 69%. Compared with patients with Charlson scores of 0, patients with
      scores of 1 to 2 had age-adjusted 1-year mortality rate ratios (MRRs) of 1.60 in
      1995 to 1997, increasing to 2.67 in 2004 to 2006. For patients with Charlson
      scores of 3 or higher, the adjusted MRR increased from 3.11 in 1995 to 1997 to
      5.08 in 2004 to 2006. CONCLUSIONS: Comorbidity was present in more than one-third
      of prostate cancer patients and was a negative prognostic factor. Although
      prostate cancer survival generally has improved in Denmark in recent years, no
      improvement was found among those with high levels of comorbidity.

PMID- 18342918
TI  - Histotripsy: minimally invasive technology for prostatic tissue ablation in an in
      vivo canine model.
AB  - OBJECTIVES: Symptoms of benign prostatic hyperplasia affect men increasingly as
      they age. Minimally invasive therapies for the treatment of benign prostatic
      hyperplasia continue to evolve. We describe histotripsy, a noninvasive,
      nonthermal, focused ultrasound technology for precise tissue ablation, and report
      the initial results of using histotripsy for prostatic tissue ablation in an in
      vivo canine model. METHODS: An annular 18-element, 750-kHz, phased-array
      ultrasound system delivered high-intensity (22 kW/cm(2)), ultrasound pulses (15
      cycles in 20 ms) at pulse repetition frequencies of 100 to 500 Hz to canine
      prostates. Eight lateral lobe and nine periurethral treatments were performed in
      11 anesthetized dogs. Diagnostic ultrasound transducers provided in-line and
      transrectal imaging. Retrograde urethrography was performed before and after the
      periurethral treatments. After treatment, the prostates were grossly examined,
      sectioned, and submitted for histologic examination. RESULTS: In the lateral lobe
      treatments, a well-demarcated cavity containing liquefied material was present at
      the ablation site. Microscopically, the targeted volume was characterized by the
      presence of histotripsy paste (debris, absent cellular structures). A narrow
      margin of cellular injury was noted, beyond which no tissue damage was apparent.
      The periurethral treatments resulted in total urethral ablation or significant
      urethral wall damage, with visible prostatic urethral defects on retrograde
      urethrography. Real-time ultrasound imaging demonstrated a dynamic hyperechoic
      zone at the focus, indicative of cavitation and suggesting effective tissue
      ablation. CONCLUSIONS: The results of our study have shown that histotripsy is
      capable of precise prostatic tissue destruction and results in subcellular
      fractionation of prostate parenchyma. Histotripsy can also produce prostatic
      urethral damage and thereby facilitate drainage of finely fractionated material
      per urethra, producing immediate debulking.

PMID- 18342919
TI  - Rare case of atypical epitelioid hemangioma of penis initially misdiagnosed as
      Peyronie's disease: report with clinical, radiologic, and immunohistochemical
      analysis.
AB  - We report a rare case of atypical epithelioid hemangioma of the penis in a 42
      year-old man with a painful penile dorsal nodule, first misdiagnosed on simple
      penile ultrasonography as Peyronie's disease. Even though the patient underwent
      treatment, the lesion improved and a penile echo-color Doppler scan showed
      abundant vascularization. After local excision, the pathologic diagnosis was
      atypical epithelioid hemangioma (central epithelioid cells bordered by immature
      vessels), with immunohistochemical positivity for CD31 and CD34 and negativity
      for epithelial membrane antigen. At 12 months after surgery, the patient was free
      of disease. Penile echo-color Doppler ultrasonography is essential to perform a
      differential diagnosis between Peyronie's disease from other penile nodular
      diseases.

PMID- 18342920
TI  - Additional benefit of laparoscopy for nonpalpable testes: finding a contralateral
      patent processus.
AB  - OBJECTIVES: To determine the incidence of contralateral patent processus
      vaginalis discovered at laparoscopy in patients presenting with a unilateral
      nonpalpable testis. METHODS: From August 1997 through February 2006, 159 boys
      underwent laparoscopic exploration for a unilateral nonpalpable testis. The data
      were retrospectively reviewed to determine the incidence of contralateral
      patency, and the results were analyzed with respect to age at repair and side and
      size of the unilateral nonpalpable testis. RESULTS: The median age of the
      patients was 1.2 years (range 2 months to 16 years). The nonpalpable testis was
      on the left side in 100 patients (63%) and on the right side in 59 (37%). The
      testis was absent in 13 patients (8%), atrophic in 78 (49%), and of normal size
      in 68 (42%). The overall incidence of a contralateral patent processus vaginalis
      was 19% (30 of 159). A contralateral patent processus vaginalis was seen in 21%
      of the boys younger than 2 years old, 19% of boys 2 to 5 years old, and 12% of
      boys older than 5 years. The incidence of a contralateral patent processus
      vaginalis was no different for patients with right (20%) versus left (18%)
      nonpalpable testes. Patients with normal-size testes (34%) had a much greater
      rate of a contralateral patent processus vaginalis than did those with an
      atrophic/absent testis (8%) (P <0.001). CONCLUSIONS: Our data suggest that the
      incidence of a contralateral patent processus vaginalis is considerable in
      patients presenting with a unilateral nonpalpable testis. This is another benefit
      of laparoscopy in patients with nonpalpable testes.

PMID- 18342921
TI  - Distribution of lymphatic vessel network in normal urinary bladder.
AB  - OBJECTIVES: The lymphatic vessel endothelial hyaluronan receptor (LYVE-1) is a
      novel lymphatic vessel marker that is expressed on lymph vessel endothelial
      cells. The objective of this study was to determine the LYVE-1 expression
      patterns in normal urothelium and to compose the geometric topography of the
      lymphatic network. METHODS: Immunohistochemical staining for LYVE-1 and von
      Willebrand factor was performed to assess the differences in the distribution of
      lymphatic vessels between the components in the urinary bladder. The sizes of the
      individual lymphatic vessels were categorized as small, medium, and large. To
      compare the lymphatic density (counts per square millimeter), the number of
      lymphatic vessels of the five random areas was counted in each specimen. RESULTS:
      LYVE-1 expression and the lymphatic density of the muscularis propria were
      significantly greater than those of other layers, including the epithelium,
      lamina propria, perivesical fat, and serosa (P <0.0001). The size of the
      lymphatic vessels in the muscularis propria was significantly smaller than that
      in the other layers (P <0.0001). The greatest distribution of the lymphatic
      vessels was identified in the border areas consisting of the lamina propria and
      muscular propria or the muscular propria and adventitia, including the
      perivesical fat and serosa. CONCLUSIONS: We have developed a new type of color
      geometric topography to accurately exhibit the distribution of that complex
      network. Lymphatic vessels, although small, are predominately distributed in the
      muscularis propria in the normal urothelium compared with that in the other
      layers. The LYVE-1 antibody was a useful specific marker for the illustration of
      the lymphatic vessel in conventional paraffin-embedded specimens of the urinary
      bladder.

PMID- 18342922
TI  - The University of Michigan experience with percutaneous nephrostolithotomy for
      urinary matrix calculi.
AB  - OBJECTIVES: To evaluate commonalities in presentation and long-term efficacy of
      treatment by percutaneous nephrostolithotomy of matrix stones, a rare form of
      urinary calculi. METHODS: The clinical data of 9 consecutive patients with
      urinary matrix calculi in 11 kidneys treated at our institution between 1995 and
      2007 were retrospectively reviewed. RESULTS: The matrix component in all 11
      kidneys was successfully treated with percutaneous nephrostolithotomy, with few
      complications. Among 8 patients (9 kidneys) with follow-up, none has had
      recurrence of matrix stones after a mean follow-up of 3.8 years. Along with
      previously known risk factors for matrix stones, such as urinary tract infections
      and renal insufficiency, we identified smoking as another possible risk factor.
      Long-term antimicrobial prophylaxis was used in only 1 patient and thus does not
      seem necessary for prevention of recurrence. CONCLUSIONS: Matrix stone treatment
      with percutaneous nephrostolithotomy is durable and should remain the treatment
      modality of choice.

PMID- 18342923
TI  - Fesoterodine dose response in subjects with overactive bladder syndrome.
AB  - OBJECTIVES: To compare the efficacy of fesoterodine 4 mg versus 8 mg in treating
      subjects with overactive bladder (OAB) syndrome. METHODS: This is a pooled
      analysis of data from 2 randomized placebo (PBO)-controlled phase III trials.
      Eligible subjects with frequency and urgency or urgency urinary incontinence
      (UUI) were randomized to PBO or fesoterodine 4 or 8 mg for 12 weeks. Subjects
      assessed efficacy using 3-day bladder diaries recording the time of each void,
      urgency, and incontinence episode. Endpoints included treatment response (based
      on a 4-point Treatment Benefit scale) and change from baseline in micturitions,
      UUI episodes, mean volume voided, urgency episodes, and continent days. We
      assessed tolerability and safety by evaluating adverse events, residual urine
      volume, laboratory parameters, and treatment withdrawals. RESULTS: At the end of
      treatment, both doses of fesoterodine showed statistically significant
      improvements in all efficacy endpoints versus PBO (P <0.01). These effects were
      seen 2 weeks after initiation of treatment (the earliest evaluation point) and
      were sustained throughout the treatment period. Fesoterodine 8 mg performed
      significantly better than fesoterodine 4 mg in improving all diary variables (P
      <0.05) except micturition frequency, demonstrating a dose-response relationship.
      Adverse events reported more frequently with fesoterodine than with PBO included
      dry mouth, constipation, and urinary tract infection. CONCLUSIONS: Both
      fesoterodine 4 and 8 mg are effective in improving OAB symptoms. The higher 8-mg
      dose provides additional benefit compared with the lower dose in improving most
      bladder diary variables, thus offering the possibility of dose flexibility and
      titration.

PMID- 18342924
TI  - The effect of ureteral stent placement on post-ureteroscopy complications: a meta
      analysis.
AB  - OBJECTIVES: To determine, by systematic review and meta-analysis of all
      randomized controlled trials examining ureteral stent placement after
      ureteroscopy, whether the presence or absence of a stent was associated with
      postoperative complications. METHODS: All randomized clinical trials of ureteral
      stent placement after ureteroscopy were identified with PubMed. The primary
      outcome was the occurrence of a urologic complication, defined as secondary
      procedure, emergency department evaluation, or hospital admission. The
      complication rates were compared between the stented (treatment) and unstented
      (control) arms of each trial as a risk difference, pooled as a weighted average
      across all studies, using both fixed and random-effects models. RESULTS: Ten
      trials were identified, with a total of 891 subjects. Patients undergoing
      ureteral stent placement after ureteroscopy had a 4% lower occurrence of urologic
      complications (95% confidence interval -10.1%, 1.8%). This difference, however,
      failed to reach statistical significance after accounting for heterogeneity in
      the data (P = 0.175). CONCLUSIONS: There is a slightly lower absolute risk of
      complication associated with the placement of a ureteral stent after
      ureteroscopy. However, meta-analysis of the present literature does not detect a
      significant difference in outcome between patients who undergo ureteral stent
      placement after ureteroscopy and those who do not.

PMID- 18342925
TI  - Macroscopic hematuria in patient with myelofibrosis caused by extramedullary
      hematopoiesis of bladder.
AB  - Extramedullary hematopoiesis (EMH) is a physiologic process in fetal life.
      However, after birth, its occurrence is abnormal, and it develops when
      hematopoiesis in the bone marrow is disturbed, such as occurs in many hematologic
      disorders. EMH can become symptomatic, depending on its extent and location. We
      describe the case of a 67-year-old man with postpolycythemic myelofibrosis who
      presented clinically with macroscopic hematuria due to EMH in the bladder. EMH in
      the bladder is extremely rare but illustrates the importance of an adequate
      pathologic assessment of transurethral resection chips, especially in patients
      with underlying disease.

PMID- 18342926
TI  - Prostate-specific antigen kinetics in screen-detected prostate cancer in Japan.
AB  - OBJECTIVES: It would be of value to compare the features of prostate cancer
      detected in various screening series around the world. Recently, some studies
      have demonstrated the value of pretreatment prostate-specific antigen (PSA)
      kinetics in predicting the outcome of radical prostatectomy and radiotherapy for
      men with localized prostate cancer. Therefore, the distribution of PSA velocity
      (PSAV) or PSA doubling time in screen-detected prostate cancer might be objective
      parameters to investigate how well each national screening system is working.
      METHODS: From 1992 to 2004, 957 men with prostate cancer were detected by
      screening in Gunma Prefecture, Japan. Of those, 275 men (29%) detected with
      consecutive screening tests participated in the present study. The PSAV was
      calculated by the PSA change between the most recent screening test and cancer
      diagnosis and also by linear regression analysis. The PSA doubling time was also
      calculated for 146 men who underwent screening at least three times. RESULTS: The
      median PSAV was 1.3 ng/mL/yr in those with Stage T1cN0M, 1.1 ng/mL/yr in those
      with T2N0M0, and 2.1 ng/mL/yr in those with T3N0M0. The percentage of men with a
      PSAV (linear regression analysis) greater than 2.0 ng/mL/yr was 13%, 12%, and 49%
      in men with clinical Stage T1cN0M0, T2N0M0, and T3N0M0, respectively. The median
      PSA doubling time was 57.1, 51.7, and 28.0 months for those with T1cN0M0, T2N0M0,
      and T3N0M0, respectively. CONCLUSIONS: Patients with prostate cancer with
      aggressive features are still detected in the population-based screening system
      in Japan. Even in Japan, where PSA screening is perhaps the most widespread among
      Asian countries, the screening system might be still immature compared with the
      systems in the United States and Western Europe.

PMID- 18342927
TI  - Bcl-XL and Bcl-2 expression in bilharzial squamous cell carcinoma of the urinary
      bladder: which protein is prognostic?
AB  - OBJECTIVES: Bcl-2 and Bcl-XL are the most important antiapoptotic members of the
      Bcl-2 family frequently overexpressed in bladder cancer. Overexpression of Bcl-XL
      bilharzial-related bladder cancer was associated with tumor progression. However,
      the negative prognostic value of Bcl-2 expression is still questionable. This
      work studied the expression of Bcl-XL and Bcl-2 immunohistochemically in
      bilharzial-related squamous cell carcinoma of the urinary bladder and determined
      their prognostic value in relation to recurrence after radical cystectomy.
      METHODS: A total of 72 patients with muscle-invasive bilharzial squamous cell
      carcinoma of the urinary bladder underwent radical cystectomy at our institution.
      The specimens were examined immunohistochemically for Bcl-XL and Bcl-2
      expression. The patients were followed up for 3 years or until recurrence. The
      expression of Bcl-XL and Bcl-2 were related to the other prognostic indicators
      and patient survival. RESULTS: The expressions of both Bcl-2 and Bcl-XL were
      significantly different according to the grade of malignancy. Bcl-XL expression
      was significantly related to tumor recurrence, but Bcl-2 expression was not.
      CONCLUSIONS: To our knowledge, the present study is the first report of a
      negative prognostic value for Bcl-XL in bilharzial squamous cell carcinoma of the
      urinary bladder. However, this is another negative report on the prognostic value
      of bcl-2 in bilharzial bladder tumors.

PMID- 18342928
TI  - Urologic disease burden in the United States: veteran users of Department of
      Veterans Affairs healthcare.
AB  - OBJECTIVES: To determine the disease burden, measured by resource utilization, of
      four urologic conditions among veteran users of U.S. Department of Veterans
      Affairs (VA) healthcare services and to assess variations by selected
      sociodemographic characteristics. METHODS: We applied expert-derived diagnosis
      clusters to establish four patient cohorts from a population of U.S. veterans
      aged 18 years and older with at least one outpatient visit in a VA healthcare
      facility in fiscal year 2001 (n = 3,691,519): (1) benign prostatic
      hyperplasia/lower urinary tract symptoms (BPH/LUTS), (2) kidney stones (KS), (3)
      urinary tract infections (UTI), and (4) urinary incontinence (UI). We identified
      patients with qualifying diagnosis codes associated with outpatient visits in the
      national VA Outpatient Clinic file, thereby generating case counts for each
      diagnostic category. RESULTS: Among veteran users of VA healthcare services, when
      defined as the primary reason for the visit, the prevalence of BPH/LUTS was 4811
      per 100,000 veterans (4.8%); the prevalence of KS was 597 per 100,000 (0.6%); the
      prevalence of UTI was 4265 and 1719 per 100,000 female and male veterans,
      respectively (4.3% and 1.7%); and the prevalence of UI was 2161 and 515 per
      100,000 female and male veterans, respectively (2.2% and 0.5%). Prevalence of
      these conditions when ascertained by capturing diagnoses appearing as secondary
      reasons for a physician visit was much higher. CONCLUSIONS: Although we expected
      the prevalence of urologic conditions to be high among veterans who use the VA
      system for care, we found the burden of urologic disease among veterans to be
      comparable to other national data sets. Prevalence estimates based on primary
      diagnosis, rather than secondary or "any" diagnosis, significantly underestimated
      the disease burden among veterans.

PMID- 18342929
TI  - Delayed diagnosis of prostate cancer with neuroendocrine differentiation after
      laser TURP.
AB  - Laser transurethral resection of the prostate (TURP) is becoming widely used for
      surgical management of lower urinary tract symptoms from benign prostatic
      hyperplasia. Yet, one drawback to laser vaporization is the lack of a prostatic
      tissue sample for pathologic evaluation. We report the case of a 57-year-old man
      who presented with urinary obstruction, a normal digital rectal examination and a
      prostate-specific antigen level of 0.44 ng/mL. The patient then underwent
      transrectal ultrasonography to determine the size of his prostate (60 g). On the
      basis of these normal findings, laser TURP was performed. The patient's symptoms
      did not improve after the procedure, and cystoscopy confirmed continued prostatic
      obstruction. The patient subsequently underwent bipolar TURP, and the pathologic
      examination of the prostate chips revealed highly aggressive prostate
      adenocarcinoma with neuroendocrine differentiation. We discuss the potential
      drawbacks of laser TURP in the diagnosis of clinically undetectable prostate
      cancer.

PMID- 18342930
TI  - Fear of recurrence, symptom burden, and health-related quality of life in men
      with prostate cancer.
AB  - OBJECTIVES: To examine the contributions of fear of recurrence and the more
      commonly examined treatment-related symptoms to the health-related quality of
      life (HRQOL) of men treated for localized prostate cancer. METHODS: A total of
      730 men with localized disease were identified from the Cancer of the Prostate
      Strategic Urologic Research Endeavor, a national, prospective study of men with
      prostate cancer. Pre- to post-treatment changes in fear of recurrence, treatment
      specific symptoms and burden, comorbidities at diagnosis, number of new symptoms,
      and post-treatment HRQOL data were analyzed. RESULTS: Linear regression, adjusted
      for clinical and demographic characteristics, showed that improved fear of
      recurrence (P <0.01), higher number of post-treatment symptoms (P <0.01), and
      improved bowel function (P <0.01) significantly predicted better mental health
      scores. For physical health, improved urinary bother (P <0.01) and lower number
      of post-treatment symptoms (P <0.01) were associated with better physical health.
      CONCLUSION: Understanding men's fears about cancer recurrence and how these fears
      influence physical and mental health are important components of providing care
      to this growing population.

PMID- 18342931
TI  - Vesicovaginal fistula repair with rectus abdominus myofascial interposition flap.
AB  - OBJECTIVES: Complex, recurrent vesicovaginal fistulas (VVFs) can be very
      challenging to repair and often require interposition of nonirradiated, well
      vascularized tissue between the urinary system and vagina. We report our
      experience using a rectus abdominus myofascial (RAM) interposition flap for VVF
      repair. METHODS: A retrospective analysis was performed to identify patients who
      had undergone VVF repair with RAM interposition. Data were collected focusing on
      preoperative patient characteristics, etiology of VVF, intraoperative parameters,
      including surgical techniques, and postoperative patient outcomes. RESULTS: We
      used a RAM interposition flap for VVF repair in 5 patients. All VVFs had
      developed postoperatively; no patient had received radiotherapy. VVF developed
      after total abdominal hysterectomy (TAH) or radical cystectomy in 3 and 2 cases,
      respectively. Both cases of VVF after radical cystectomy occurred in conjunction
      with orthotopic diversion (neobladder-vaginal fistula). In 3 patients with post
      TAH VVF, a total of five previous failed repairs were attempted before RAM
      interposition. In 1 patient with a neobladder-vaginal fistula, who had received
      adjuvant chemotherapy, RAM interposition failed, and the patient ultimately
      required cutaneous urinary diversion after two subsequent failed attempts at
      repair (68 months of follow-up). The remaining 4 patients (80%) had no evidence
      of recurrent VVF or voiding abnormalities at a mean follow-up of 19 months (range
      8 to 32). CONCLUSIONS: Rectus abdominus muscle can be a successful interposition
      flap during repair of complex, recurrent VVF. In our experience, this has been
      successful in most cases, particularly in younger patients with nonmalignant
      processes.

PMID- 18342932
TI  - A candidate precursor to pelvic serous cancer (p53 signature) and its prevalence
      in ovaries and fallopian tubes from women with BRCA mutations.
AB  - BACKGROUND: Early serous carcinomas predominate in the fimbria of women with BRCA
      mutations (BRCA+). An entity in non-neoplastic mucosa sharing several properties
      of early serous carcinomas--the "p53 signature"--has been described in the distal
      fallopian tube and proposed as a precursor to serous carcinomas. This study
      compared the prevalence of p53 signatures in ovarian cortical inclusion cysts
      (CICs) and fallopian tubes from BRCA+ women and explored their relationship.
      DESIGN: All tissues from 75 completely excised ovaries and tubes obtained during
      prophylactic surgery were studied by conventional microscopy, immunostaining for
      p53, and in selected cases, gamma-H2AX (DNA damage). P53 signatures were defined
      as 12 or more consecutive p53-positive secretory cell nuclei. Their prevalence in
      fallopian tubes and CICs was recorded, compared to an existing database of
      consecutive women without a suspicion of BRCA+ or ovarian cancer, and correlated
      with the number of CICs. RESULTS: Tubal p53 signatures were detected in 29 of 75
      cases (38%); 20 of 30 (66%) signatures examined were gamma-H2AX-positive. One
      ovary contained a small gamma-H2AX negative p53 signature on the ovarian surface;
      no p53 signatures were identified in CICs. The prevalence of BRCA+ p53 tubal
      signatures was similar to that of women with unknown BRCA status (38 v 33%).
      Presence of p53 signatures did not correlate with number of CICs. CONCLUSIONS:
      p53 signatures were common in the fallopian tubes of BRCA+ women, were not
      identified in CICs, and did not correlate with the latter. The tubal p53
      signature merits serious consideration as an important early event in serous
      carcinogenesis in BRCA+ women.

PMID- 18342933
TI  - Interaction of selected cosolvents with bovine alpha-lactalbumin.
AB  - Alpha-lactalbumin constitutes about 3% of bovine milk proteins. The preferential
      solvent interactions between selected cosolvents (sorbitol, sucrose and glycerol)
      and alpha-lactalbumin at pH 7.5 was determined using precision densitimetry. The
      preferential interaction parameter (xi(3)) and other thermodynamic parameters
      were calculated at different solvent concentrations. The xi(3) parameter was
      maximum at 30%, 45% and 40% (w/v) concentrations with the values of -0.282g/g, 
      0.171g/g and -0.299g/g for sorbitol, sucrose and glycerol, respectively. Thus the
      principal driving energy in the system being preferential hydration and mutual
      exclusion of bulk solvent. There was only a marginal change in the CD spectra of
      the protein with these cosolvents indicating the integrity of secondary
      structures. The results of thermal denaturation measurements indicated an
      increase in thermal stability of alpha-lactalbumin with these cosolvents. In the
      presence of 30% sorbitol there was an increase in the apparent thermal transition
      temperature (apparent T(m)) from 65 to 71 degrees C. These results indicate that
      the selected cosolvents in this study stabilizes alpha-lactalbumin without
      altering the structure of the protein.

PMID- 18342934
TI  - Placental mesenchymal dysplasia with beckwith-wiedemann syndrome fetus in the
      context of biparental and androgenic cell lines.
AB  - Placental mesenchymal dysplasia (PMD) is a distinct placental disorder that may
      coexist with a normal fetus. In one-third of cases, the fetus exhibits Beckwith
      Wiedemann Syndrome (BWS). In the present study, we report a case of PMD changes
      associated with an unusual genetic constitution. Pathological examination showed
      an enlarged placenta with a mixture of normal but also numerous clusters of grape
      like fluid-filled vesicles confined to the stem villi without trophoblast
      proliferation. Some stem villi contained many large vessels filled by partially
      organized thrombi consistent with PMD. The fetus presented an enlarged liver and
      cytomegaly in the adrenal glands, hyperplastic islets of Langerhans in the
      pancreas, and some microcysts with cuboidal epithelium in the kidneys. These
      findings suggest the Beckwith-Wiedemann syndrome phenotype. DNA genetic markers
      showed three alleles for three independent markers and two alleles for the 12
      others. Fluorescent in situ hybridization (FISH) demonstrated that villous
      trophoblast and fetal tissues are diploid. The haploid paternal complement found
      in the androgenetic cells was different from that found in biparental cells,
      suggesting a double fertilization event. Preferential distribution of the
      androgenetic cells into the placenta explains the predominance of molar villi
      with an apparently normal fetus. This represents a well-documented case of
      androgenic and biparental mixture of cell types in both fetal and placental
      tissues.

PMID- 18342935
TI  - Anti-fas activating antibody enhances trophoblast outgrowth on endometrial
      epithelial cells by induction of P38 MAPK/JNK-mediated apoptosis.
AB  - In species with hemochorial placentation, such as the mouse and human,
      trophoblast cells of the implanting blastocyst induce apoptosis and displace
      endometrial epithelial cells (EEC) to cross the luminal epithelium of the
      endometrium. Since Fas and Fas ligand (FasL) are expressed in EEC and trophoblast
      cells respectively and mitogen-activated protein kinases (MAPKs) mediate Fas
      induced apoptosis, the roles of Fas/FasL and MAPK signaling in trophoblast-EEC
      interactions were studied. By co-culturing BeWo trophoblast spheroids with RL95-2
      EEC monolayers to mimic blastocyst-endometrial interactions, we found that
      trophoblast spheroid outgrowth on EEC was significantly enhanced by anti-Fas
      activating antibody. Since anti-Fas activating antibody had no effect on spheroid
      expansion on EEC-free culture surfaces, its enhancing effect on spheroid
      outgrowth on EEC may be mediated by acting on EEC to facilitate trophoblast
      induced EEC apoptosis and displacement. Valyl-alanyl-aspartyl-[O-methyl]
      fluoromethylketone (VAD-FMK) staining showed that the percentage of apoptotic EEC
      at the spheroid-EEC interface was markedly increased by anti-Fas activating
      antibody. Moreover, the pancaspase inhibitor benzyloxycarbonyl-VAD-FMK was able
      to suppress the enhancing effect of anti-Fas activating antibody on spheroid
      expansion on EEC. Upon anti-Fas activating antibody stimulation, both p38 MAPK
      and c-Jun NH(2)-terminal kinase (JNK) were activated. Furthermore, the anti-Fas
      activating antibody-enhanced EEC apoptosis and spheroid expansion on EEC were
      significantly inhibited by the p38 MAPK inhibitor SB203580 and JNK inhibitor
      SP600125. Our results establish that anti-Fas activating antibody could activate
      p38 MAPK and JNK to induce EEC apoptosis, thereby promoting trophoblast outgrowth
      on EEC.

PMID- 18342936
TI  - Inequality, privacy, and mental health.
AB  - The state's mental health power is standardly understood in terms of the state's
      power to intervene with persons or populations to address mental health problems.
      This article advances a more expansive view of the state's mental health power,
      one which seeks to capture those exercises of state power that do not directly
      concern mental health but that nevertheless can have a profound effect on mental
      well-being. The article considers two features of contemporary American society
      that implicate the state in conditions that undermine, or threaten to undermine,
      mental health. The first concerns the impact of poverty and inequality on mental
      health. The second concerns the threat to the self posed by measures that would
      significantly erode privacy. The article argues that a greater commitment to
      liberal principles of equality and tolerance is crucial to overcoming the perils
      for mental health that poverty and losses of privacy generate.

PMID- 18342937
TI  - Does the nutrition profile of vitamins, fatty acids and microelements counteract
      the negative impact from organohalogen pollutants on bone mineral density in
      Greenland sledge dogs (Canis familiaris)?
AB  - There is a great need for understanding the impact from dietary OHCs
      (organohalogen compounds) on bone mineral composition - and thereby osteoporosis 
      in especially arctic wildlife such as polar bears (Ursus maritimus) as well as
      humans. For that purpose, we measured BMD (bone mineral density) by DXA scanning
      (g/cm(-2)) in 15 age and weight normalized sledge dog (Canis familiaris) bitches
      and their 26 pups divided into a control group (n=26) given 50-200 g/day clean
      pork (Suis scrofa) fat and a treated group (n=15) given 50-200 g/day OHC polluted
      minke whale (Balaenoptera acutorostrata) blubber as main lipid sources. The
      results showed that BMD increased significantly with age (linear regression:
      p<0.0001, r(2)=0.83, n=41) while no sex difference was found in the F-generation
      (two-way ANOVA: all p>0.3). No differences in BMD(femur) or BMD(vertebrae)
      between exposed and control individuals in the bitch generation were found
      (linear mixed effect model: both p>0.38). Likewise, no difference between exposed
      and control subadults and juveniles in the F-generation was found (two-way ANOVA:
      all p>0.33). Correlation analyses between BMD(femur), BMD(vertebrae) and groups
      of OHCs, respectively, did not show any statistically significant relationships
      nor a clear or decreasing trend (Pearson's: p: 0.07-0.78; r: -0.2-0.59; n: 10
      18). As the groups were similar regarding genetics, age and sex are the only
      factors that can explain this observation. Either the pollutants did not have an
      impact on BMD using the present time frame and OHC concentrations (threshold
      levels not reached), or the difference in food composition (mainly vitamins and
      n3 fatty acids) conceal the potential OHC impact on BMD. Such information is
      important when evaluating the positive and negative health consequences from
      eating polluted marine species.

PMID- 18342938
TI  - Converting Toxic Equivalents (TEQ) of dioxins and dioxin-like compounds in fish
      from one Toxic Equivalency Factor (TEF) scheme to another.
AB  - Toxic Equivalency Factors (TEFs) are an essential part of the Toxic Equivalent
      (TEQ) concept and have evolved for dioxins/dioxin-like compounds over the last
      two and half decades. Therefore, it is difficult to compare past and current TEQs
      that are reported using different TEFs without explicitly mentioning underlying
      congener concentrations. Using what likely is the largest known dioxin/furan
      (PCDD/F) and dioxin-like polychlorinated biphenyl (dl-PCB or DLP) fish database,
      here we present regression models that can facilitate conversion of a fish TEQ
      from an old to a newer TEF scheme. The results show that the mammalian PCDD/F-TEQ
      based on the latest TEF(WHO-05) is about 7.5% lower than that based on TEF(WHO
      98). The mammalian DLP-TEQ(WHO-05) is on average 25-26% lower than almost
      identical DLP-TEQ(WHO-94) and DLP-TEQ(WHO-98). Total-TEQ(WHO-05) is on average
      22% lower than Total-TEQ(WHO-98). According to the current toxicological
      standards for dioxins/furans, all previous major TEF schemes except TEF(Germany
      85) and TEF(USEPA-87) were conservative (i.e., higher) in estimating TEQs. The
      major (> 75%) contribution to PCDD/F-TEQ(WHO-05) is from 2,3,7,8-TCDD (33%),
      1,2,3,7,8-PCDD (26%), 2,3,7,8-TCDF (10%), and 2,3,4,7,8-PCDF (9%). The DLP
      TEQ(WHO-05) is dominated by PCB-126 which on average contributes about 88%. The
      DLP-TEQ generally contribute > 70% of Total-TEQ. When reporting TEQs, we
      recommend that the underlying congener specific concentrations are presented, TEF
      scheme used is clearly stated, names of compounds included are explicitly
      expressed, and TEQs are identified accordingly (e.g., DLP-TEQ, PCDD/F-TEQ, Total
      TEQ).

PMID- 18342939
TI  - Syndecan-2 and -4 expressed on activated primary human CD4+ lymphocytes can
      regulate T cell activation.
AB  - Syndecans bind to cell adhesion molecules, growth factors and cytokines, and can
      act as coreceptors, and in this way modulate leukocyte cell function. Here,
      expression of the syndecans on primary human CD4 T cells was examined. Cell
      stimulation dramatically increased the amount of syndecan-4, and in a lower
      extent that of syndecan-2. Expression of syndecan-2 and -4 show different
      induction kinetics. Whereas syndecan-4 expression is fast and significant, that
      of syndecan-2 is more delayed and short-lived decreasing its mRNA expression at
      day 4. Both CD45RA+ naive and CD45RA- memory CD4 T cells express syndecan-2 and 
      4 upon activation. When incubated with human peripheral blood lymphocytes in a
      mixed leukocyte reaction, anti-syndecan-4 but not anti-syndecan-2 antibodies,
      decreased T cell proliferation. However, cross-linking of cell-bound syndecan-2
      or syndecan-4 via immobilized antibodies blocked proliferation and decreased TNF
      production of T cells in the presence of optimal levels of anti-CD3. These
      findings suggest that syndecan-2 and -4 act as inhibitors of T cell activation.
      We also investigated the role that MAPK signalling pathways play in control of
      syndecan expression in T cells. We show that production of syndecan-2 but not
      syndecan-4 requires signaling via p38 MAP kinase alpha/beta in T CD4 cells. As
      mechanisms that confer syndecan-2 expression are unknown, we analyse the
      chromatin hypersensitivity of syndecan-2 promoter proximal region in Jurkat T
      cells and endothelial cells. The analysis reveals a chromatin accessible site in
      the +3.5kb intronic region, concomitant with a region showing high evolutionary
      conservation. We isolate and analyse 5'-flanking regions of human syndecan-2
      gene, by transfection assays. The +3.5kb hypersensitive site in the intronic
      region demonstrates basal promoter activity in Jurkat. This study provides
      evidence for the up-regulation of syndecan-2 and -4 in human primary CD4 T cells
      during in vitro activation and suggest an inhibitory role for these syndecans in
      CD4 T cells.

PMID- 18342940
TI  - A role for matrix metalloproteinases in granulocyte infiltration and testicular
      remodelation in a seasonal breeding teleost.
AB  - The testicular cystic structure and the abrupt morphological changes that the
      fish testis undergoes during the reproductive cycle (RC) make it an interesting
      model for studying the regulation of spermatogenesis, in particular the role of
      matrix metalloproteinases (Mmps). The gilthead seabream is a seasonal breeding
      teleost whose testis undergoes drastic remodeling events, especially during the
      post-spawning stage when a massive infiltration of a immune cell type, the
      acidophilic granulocytes, occurred. Bearing this in mind, we studied the gilthead
      seabream testis gelatinolytic activities involved in migration and tissue
      remodeling and its regulation by endocrine, immune and tissue stimuli. Thus, we
      demonstrated that the germinal epithelium of the testis showed gelatinolytic
      activity during spermatogenesis and post-spawning but not during resting, when
      only scarce interstitial cells were stained. Moreover, the precursor and mature
      forms of two gelatinases, Mmp2- and Mmp9-like, were active in the gonad, whose
      activities were up-regulated by 17beta-estradiol (E(2)) but not by
      lipopolysaccharide (LPS)/bacterial DNA (VaDNA) in testicular cell suspensions.
      E(2) and LPS/VaDNA also up-regulated a variety of cytokines and chemokines. We
      also cloned mmp9, mmp13, tissue inhibitors of Mmps (timp)-2a and timp2b genes and
      found that all of them were expressed in the gonad in a RC stage-dependent
      manner. Interestingly, mmps and timps were highly expressed by the testicular
      acidophilic granulocytes. Moreover, in these cells, the gelatinolytic activity
      seemed to correspond to the precursor and mature forms of putative Mmp2 and Mmp9
      gelatinases, while the main gelatinolytic activity seemed to correspond to the
      mature form of Mmp2 in head-kidney acidophilic granulocytes. Finally, although
      none of the stimuli used were able to induce the gelatinolytic activity of Mmp9
      like in head-kidney acidophilic granulocytes, the expression of mmp9, timp2a and
      timp2b were all up-regulated by LPS/VaDNA in these cells, while only mmp9 and
      timp2a expression increased upon stimulation with gelatin.

PMID- 18342941
TI  - Optic disc and peripapillary morphology in unilateral nonarteritic anterior
      ischemic optic neuropathy and age- and refraction-matched normals.
AB  - PURPOSE: To compare optic disc morphologic features and peripapillary retinal
      nerve fiber layer (RNFL) thickness between the unaffected eyes of patients with
      unilateral nonarteritic anterior ischemic optic neuropathy (NAION) and their
      affected eyes and the eyes of age- and refraction-matched normal control
      subjects. DESIGN: Cross-sectional comparative study. PARTICIPANTS: Thirty-one
      patients with unilateral NAION and 62 age- and refraction-matched normal control
      subjects. METHODS: Optic disc morphologic features and peripapillary RNFL
      thickness were evaluated in both eyes of patients with unilateral NAION and in
      one randomly chosen eye of the normal control subjects. MAIN OUTCOME MEASURES:
      Optic disc and cup parameters were measured using the Heidelberg Retina Tomograph
      II (Heidelberg Engineering GmbH, Dossenheim, Germany), and RNFL thickness was
      measured by scanning laser polarimetry with variable corneal compensation (GDx
      VCC; Carl Zeiss Meditec, Dublin, CA). RESULTS: There was no significant
      difference in the disc area between the NAION affected eyes and the unaffected
      fellow eyes. The cup area, cup-to-disc area ratio, cup volume, and cup shape
      measure were greater, whereas the peripapillary RNFL thickness was smaller in the
      former than the latter (P = 0.001 to approximately 0.043). When the unaffected
      eyes of patients with NAION and the age- and refraction-matched normal control
      eyes were compared, the disc area, cup area, cup-to-disc area ratio, cup volume,
      mean cup depth, and cup shape measure were smaller in the former (P = 0.0006 to
      approximately 0.03); there was no significant difference in the RNFL thickness
      between the two (P>0.06). CONCLUSIONS: A comparison of the eyes with NAION and
      the fellow eyes indicated that the cup was slightly larger in the former than in
      the latter, suggesting the acquired enlargement of the cupping after NAION
      develops. A comparison of the unaffected fellow eyes in patients with NAION and
      the age- and refraction-matched normal control eyes suggested that a smaller disc
      area and smaller cupping were predisposing risk factors for the development of
      NAION.

PMID- 18342942
TI  - Artificial neural networks estimating survival probability after treatment of
      choroidal melanoma.
AB  - PURPOSE: To describe neural networks predicting survival from choroidal melanoma
      (i.e., any uveal melanoma involving choroid) and to demonstrate the value of
      entering age, sex, clinical stage, cytogenetic type, and histologic grade into
      the predictive model. DESIGN: Nonrandomized case series. PARTICIPANTS: Patients
      resident in mainland Britain treated by the first author for choroidal melanoma
      between 1984 and 2006. METHODS: A conditional hazard estimating neural network
      (CHENN) was trained according to the Bayesian formalism with a training set of
      1780 patients and evaluated with a test set of another 874 patients. Conditional
      hazard estimating neural network-generated survival curves were compared with
      those obtained with Kaplan-Meier analyses. A second model was created with
      information on chromosome 3 loss, using training and test sets of 211 and 140
      patients, respectively. MAIN OUTCOME MEASURES: Comparison of CHENN survival
      curves with Kaplan-Meier analyses. Representative results showing all-cause
      survival and inferred melanoma-specific mortality, according to age, sex,
      clinical stage, cytogenetic type, and histologic grade. RESULTS: The predictive
      model plotted a survival curve with 95% credibility intervals for patients with
      melanoma according to relevant risk factors: age, sex, largest basal tumor
      diameter, ciliary body involvement, extraocular extension, tumor cell type,
      closed loops, mitotic rate, and chromosome 3 loss (i.e., monosomy 3). A survival
      curve for the age-matched general population of the same sex allowed estimation
      of the melanoma-related mortality. All-cause survival curves generated by the
      CHENN matched those produced with Kaplan-Meier analysis (Kolmogorov-Smirnov,
      P<0.05). In older patients, however, the estimated melanoma-related mortality was
      lower with the CHENN, which accounted for competing risks, unlike Kaplan-Meier
      analysis. Largest basal tumor diameter was most predictive of mortality in tumors
      showing histologic and cytogenetic features of high-grade malignancy. Ciliary
      body involvement and extraocular extension lost significance when cytogenetic and
      histologic data were included in the model. Patients with a monosomy 3 melanoma
      of a particular size were predicted to have shorter survival if their tumor
      showed epithelioid cells and closed loops. CONCLUSIONS: Estimation of survival
      prognosis in patients with choroidal melanoma requires multivariate assessment of
      age, sex, clinical tumor stage, cytogenetic melanoma type, and histologic grade
      of malignancy.

PMID- 18342943
TI  - A national program director survey of the shift to competency-based education in
      ophthalmology.
AB  - PURPOSE: To assess the resources, progress, and barriers for program director
      (PD) compliance with the Accreditation Council for Graduate Medical Education
      (ACGME) mandate. DESIGN: Survey. PARTICIPANTS: Ophthalmology PDs in the United
      States. METHODS: A survey instrument was sent to all ophthalmology PDs in the
      United States. MAIN OUTCOME MEASURES: The survey instrument assessed PD tenure,
      funding, current efforts, evaluation modalities, barriers, and desired resources
      to meet the ACGME competency mandate. RESULTS: The survey was completed by 88 of
      104 (85%) PDs. Significant disparities exist between PD financial compensation
      and actual time spent performing PD duties. This disparity and lack of
      understanding by faculty of the ACGME competencies were the most frequently cited
      barriers to success in complying with the ACGME mandate. The most commonly
      utilized assessment tools are the global or 360 degrees evaluations and clinical
      evaluation exercises. CONCLUSIONS: Program directors surveyed believe they are
      not receiving adequate resources to allow them to comply with the ACGME mandate.
      Although some tools have been implemented by PDs for assessing the competencies,
      additional national and centralized resources would be helpful.

PMID- 18342944
TI  - A phase I/II study of direct intraarterial (ophthalmic artery) chemotherapy with
      melphalan for intraocular retinoblastoma initial results.
AB  - OBJECTIVE: To develop a technique that would allow us to cannulate repeatedly the
      ophthalmic artery of young children with advanced retinoblastoma, to find a dose
      of melphalan that would be tolerable and tumoricidal for retinoblastoma when
      given intraarterially, and to study the local ocular and systemic side effects of
      intraarterial melphalan in these children. DESIGN: Phase I/II clinical trial.
      PARTICIPANTS: Ten children with advanced retinoblastoma (Reese-Ellsworth V) eyes
      who were indicated for enucleation were entered into an institutional review
      board-approved protocol of ophthalmic artery infusion of melphalan to avoid
      enucleation. METHODS: Cannulation of the ophthalmic artery was performed by a
      femoral artery approach using microcatheters while the children were under
      anesthesia and anticoagulated. Chemotherapy (melphalan) was infused into the
      artery over a 30-minute period. MAIN OUTCOME MEASURES: Ophthalmic examinations,
      retinal photography, and electroretinograms were used to document local toxicity,
      whereas physical examinations and complete blood counts were used to measure
      systemic toxicity. RESULTS: The ophthalmic arteries were successfully cannulated
      in 9 cases (total, 27 times), as many as 6 times in 1 patient. Dramatic
      regression of tumors, vitreous seeds, and subretinal seeds were seen in each
      case. No severe systemic side effects (sepsis, anemia, neutropenia, fever, or
      death) occurred. No transfusions were required (red cells or platelets). Three
      patients developed conjunctival and lid edema that resolved without treatment.
      There was no toxicity to the cornea, anterior segment, pupil, or motility. One
      (previously irradiated) eye developed retinal ischemia; another eye had no
      toxicity after intraarterial chemotherapy but did develop a radiationlike
      retinopathy after brachytherapy. Vision stabilized or improved in all but 1
      patient after treatment. Electroretinograms were generally poor (advanced eyes
      were treated), but in 2 cases, the electroretinogram improved after treatment
      (and resolution of a retinal detachment). Seven eyes avoided enucleation. Two
      intraarterially treated eyes were enucleated, with no viable tumors identified
      pathologically. CONCLUSIONS: We developed a technique of direct ophthalmic artery
      infusion of melphalan for children with retinoblastoma. The technique had minimal
      systemic side effects (one patient had grade 3 neutropenia) and minimal local
      toxicity. Among the first 9 cases treated with this technique, 7 eyes destined to
      be enucleated were salvaged.

PMID- 18342945
TI  - Gender differences in susceptibility to kainic acid-induced neurodegeneration in
      aged C57BL/6 mice.
AB  - Some epidemiological studies concerning gender differences in Alzheimer's disease
      (AD) support the higher prevalence and incidence of AD in women, while most
      studies using animal models of aging have included only male subjects. It is
      still uncommon for aged males and females to be compared in the same study. In
      the present study, we investigated how age and gender influence the excitotoxic
      neurodegeneration by treating C57BL/6 mice (aged females and males as well as
      adult females and males) with kainic acid (KA) intranasally. Clinical signs,
      behavioural changes, pathological changes and astrocyte proliferation were
      tested; and the levels of brain-derived neurotrophic factor (BDNF) and nerve
      growth factor (NGF) were measured after KA treatment. The results showed that
      aged female mice were more sensitive to KA-induced excitotoxicity as demonstrated
      by severer seizure activity, increased locomotion and rearing in open-field test,
      prominent hippocampal neuronal damage, enhanced astrocyte proliferation compared
      with aged males, adult females and adult male mice. In addition, higher BDNF
      level in hippocampus of aged female mice was observed. These results denote the
      disparity of aging and gender in KA-induced hippocampal neurodegeneration and
      aged female mice are more sensitive to the excitotoxicity.

PMID- 18342946
TI  - Beta-haemolytic group A streptococci emm75 carrying altered pyrogenic exotoxin A
      linked to scarlet fever in adults.
AB  - OBJECTIVE: To determine the etiological cause of a food-borne outbreak of scarlet
      fever in adults. METHODS: Swabs from the throats of the patients and asymptomatic
      control were cultured on blood agar plates individually. Biochemical
      identification of all isolates was performed with a VITEX automated system.
      Antibiotic susceptibility was examined by using the Kirby-Bauer disc diffusion
      method. emm gene and extracellular pyrogenic exotoxins of each isolate were
      amplified by using polymerase chain reaction and subjected to DNA sequencing.
      Sequence differences between the isolated and the highly similar reference
      sequences were compared on BLAST. Bioinformatics was used to predict protein
      structures. RESULTS: Beta-haemolytic group A streptococci (GAS) emm75 were
      identified from 10 of 13 available patients. The isolates were susceptible to
      penicillin, ampicillin, vancomycin, cefatriaxone, ofloxacin, linezolid and
      quinupristin. All of the isolates carried pyrogenic exotoxin A (speA) and
      cysteine protease (speB). Isolated speA was phylogenetically different from 30
      highly similar references on BLAST. Differences in the primary sequence of the
      deduced protein were 14.37-20.12% between the speA and each of 11 references.
      Secondary protein structure of the speA was different from the references at the
      N-terminal. CONCLUSIONS: GAS emm75 encoding altered speA was responsible for the
      food-borne outbreak of scarlet fever in adults.

PMID- 18342947
TI  - Gram-negative organisms predominate in Hickman line-related infections in non
      neutropenic patients with hematological malignancies.
AB  - BACKGROUND: Catheter-related blood stream infections (CRBSI) cause significant
      morbidity and mortality in patients with hematological malignancies. Previous
      studies have identified a predominance of gram-positive organisms causing CRBSI
      but they included both neutropenic and non-neutropenic patients with solid organ
      and hematological malignancies. The aim of our study was to evaluate the
      incidence and microbiological profile of CRBSIs in a specific cohort of patients
      with hematological malignancies in their non-neutropenic phase of illness.
      METHODS: A detailed retrospective review was done from January 2003 to December
      2005 on all patients with hematological malignancies who had double-lumen non
      antibiotic impregnated tunneled CVCs (Hickman catheters) inserted in our hospital
      to identify those fulfilling our criteria for CRBSI episodes. RESULTS: Amongst
      273 evaluable patients, 61 developed CRBSI on 70 occasions. In contrast to
      previous studies, there was a predominance of gram-negative infections (68%). The
      majority (73%) of initial CRBSI episodes required catheter removal within 7 days
      of onset. Vancomycin and cefepime was the most common initial antibiotic regimen
      used. CONCLUSIONS: This study highlights the predominance of gram-negative
      infections in our cohort of non-neutropenic patients with underlying
      hematological malignancies who had Hickman catheters whose lines were not
      salvageable in the majority of cases. Empiric monotherapy with an antimicrobial
      agent with broad spectrum gram-negative cover needs to be given upfront pending
      results of the nature and sensitivity of organisms identified.

PMID- 18342948
TI  - How do mutant Nav1.1 sodium channels cause epilepsy?
AB  - Voltage-gated sodium channels comprise pore-forming alpha subunits and auxiliary
      beta subunits. Nine different alpha subtypes, designated Nav1.1-Nav1.9 have been
      identified in excitable cells. Nav1.1, 1.2 and 1.6 are major subtypes in the
      adult mammalian brain. More than 200 mutations in the Nav1.1 alpha subtype have
      been linked to inherited epilepsy syndromes, ranging in severity from the
      comparatively mild disorder Generalized Epilepsy with Febrile Seizures Plus to
      the epileptic encephalopathy Severe Myoclonic Epilepsy of Infancy. Studies using
      heterologous expression and functional analysis of recombinant Nav1.1 channels
      suggest that epilepsy mutations in Nav1.1 may cause either gain-of-function or
      loss-of-function effects that are consistent with either increased or decreased
      neuronal excitability. How these diverse effects lead to epilepsy is poorly
      understood. This review summarizes the data on sodium channel mutations and
      epilepsy and builds a case for the hypothesis that most Nav1.1 mutations have
      their ultimate epileptogenic effects by reducing Nav1.1-mediated whole cell
      sodium currents in GABAergic neurons, resulting in widespread loss of brain
      inhibition, an ideal background for the genesis of epileptic seizures.

PMID- 18342949
TI  - Automated measurement of spatial preference in the open field test with
      transmitted lighting.
AB  - New modification of the open field was designed to improve automation of the
      test. The main innovations were: (1) transmitted lighting and (2) estimation of
      probability to find pixels associated with an animal in the selected region of
      arena as an objective index of spatial preference. Transmitted (inverted)
      lighting significantly ameliorated the contrast between an animal and arena and
      allowed to track white animals with similar efficacy as colored ones. Probability
      as a measure of preference of selected region was mathematically proved and
      experimentally verified. A good correlation between probability and classic
      indices of spatial preference (number of region entries and time spent therein)
      was shown. The algorithm of calculation of probability to find pixels associated
      with an animal in the selected region was implemented in the EthoStudio software.
      Significant interstrain differences in locomotion and the central zone preference
      (index of anxiety) were shown using the inverted lighting and the EthoStudio
      software in mice of six inbred strains. The effects of arena shape (circle or
      square) and a novel object presence in the center of arena on the open field
      behavior in mice were studied.

PMID- 18342950
TI  - Automated detection and analysis of foraging behavior in Caenorhabditis elegans.
AB  - Foraging is a rapid, side-to-side movement of the nose generated by
      Caenorhabditis elegans as it explores its environment. In this paper, we present
      an automated method to detect and analyze foraging behavior of C. elegans in a
      video sequence. Several morphological image-processing methods are used to locate
      the precise nose position of the worm in each image. Then foraging events are
      detected by measuring the bending angle of the nose and investigating the overall
      bending curve using periodograms. We measure foraging-related parameters which
      have not previously been studied. The algorithm has applications in classifying
      and characterizing genetic mutations associated with this behavior.

PMID- 18342951
TI  - Changes in outpatient lithium treatment in the Netherlands during 1996-2005.
AB  - BACKGROUND: The objectives of the present study were to investigate in
      outpatients in the Netherlands between 1996 and 2005, changes in 1) the incidence
      and prevalence of lithium use and 2) lithium use patterns (discontinuation, add
      on, and switch). METHODS: Incidence and prevalence of lithium use were determined
      for each year between 1996 and 2005. In addition, we determined cumulative
      changes in lithium use (discontinuation, add-on, and switching) at three, six, 12
      and 24 months for three separate time-cohorts (1998-1999, 2000-2001 and 2002
      2003). Lastly, concomitant use of other drugs used in the treatment of bipolar
      disorders next to lithium during the 24 months after the first lithium
      prescription was determined for the three time-cohorts. RESULTS: Incidence of
      lithium use was constant at approximately 0.2 per 1000 person-years, prevalence
      increased with 26% from 0.95 to 1.2 per 1000 persons. The percentage of patients
      receiving an add-on drug used in the treatment of bipolar disorders was constant
      over the three time-cohorts, with a significant decrease in use of tricyclic
      antidepressants. Within the patient group that stopped using lithium, more
      patients switched from lithium to another agent used in the treatment of bipolar
      disorders over calendar time, and fewer patients discontinued lithium. There was
      a significant increase in the use of atypical antipsychotics and valproic acid
      next to lithium. LIMITATIONS: We did not know the specific diagnosis for which
      lithium treatment was instituted. CONCLUSION: The changes were in line with the
      increase in alternatives during the last decade and in line with Dutch
      guidelines.

PMID- 18342952
TI  - Cost-effectiveness of usual general practitioner care with or without
      antidepressant medication for patients with minor or mild-major depression.
AB  - BACKGROUND: Minor depression is common in primary care and associated with
      increased health care costs. Many mildly depressed patients are prescribed
      antidepressants, although there is insufficient information on the cost
      effectiveness of antidepressants for these patients. The objective of this study
      was to evaluate whether usual care without antidepressants is equivalent to (i.e.
      as effective as and as expensive as) usual care with antidepressants in patients
      with minor or mild-major depression. METHODS: Severity of depression was measured
      using the Montgomery Asberg Depression Rating Scale (MADRS) and quality-adjusted
      life-years (QALYs) using the EuroQol. Resource use was measured from a societal
      perspective using cost diaries. Bootstrapping was used to analyze the cost
      effectiveness data. RESULTS: Equivalence could not be shown for improvement in
      MADRS score or QALYs gained at 52 weeks. The mean (95% CI) difference in total
      costs between usual care without antidepressants and usual care with
      antidepressants was -euro751 (-3601; 1522). Using an equivalence margin of
      euro500 equivalence in costs could not be shown. In the cost-effectiveness
      analyses equivalence also could not be shown. LIMITATIONS: This study was
      underpowered for economic outcomes. Another limitation was the loss-to-follow-up.
      CONCLUSIONS: Although equivalence could not be shown in the costs and cost
      effectiveness analyses, 95% confidence intervals also did not show that usual
      care without antidepressants was vastly superior or inferior to usual care with
      antidepressants. Therefore, we recommend general practitioners to show restraint
      when prescribing antidepressants to mildly depressed patients.

PMID- 18342953
TI  - Brain structure and symptom dimension relationships in obsessive-compulsive
      disorder: a voxel-based morphometry study.
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is a clinically heterogenous
      disorder characterized by temporally stable symptom dimensions. Past inconsistent
      results from structural neuroimaging studies of OCD may have resulted from the
      effects of these specific symptom dimensions as well as other socio-demographic
      and clinical variables upon gray matter (GM) volume. METHODS: GM volume was
      measured in 25 adult OCD patients and 20 adult healthy controls using voxel-based
      morphometry (VBM), controlling for age and total brain GM volume. Univariate and
      multivariate regression analyses were carried out between regions of GM
      difference and age, age of onset, medication load, OCD severity, depression
      severity, and separate symptom dimension scores. RESULTS: Significant GM
      volumetric differences in OCD patients relative to controls were found in dorsal
      cortical regions, including bilateral BA6, BA46, BA9 and right BA8
      (controls>patients), and bilateral midbrain (patients>controls). Stepwise
      regression analyses revealed highly significant relationships between greater
      total OCD symptom severity and smaller GM volumes in dorsal cortical regions and
      larger GM volumes in bilateral midbrain. Greater age was independently associated
      with smaller GM volumes in right BA6, left BA9, left BA46 and larger GM volumes
      in right midbrain. Greater washing symptom severity was independently associated
      with smaller GM volume in right BA6, while there was a trend association between
      greater hoarding symptom severity and lower GM volume in left BA6. LIMITATIONS:
      The sample was relatively small to examine the relationship between symptom
      scores and GM volumes. Multiple patients were taking medication and had comorbid
      disorders. CONCLUSIONS: These analyses suggest dorsal prefrontal cortical and
      bilateral midbrain GM abnormalities in OCD that appear to be primarily driven by
      the effects of total OCD symptom severity. The results regarding the relationship
      between GM volumes and symptom dimension scores require examination in larger
      samples.

PMID- 18342954
TI  - Identifying differences in biased affective information processing in major
      depression.
AB  - This study investigates the extent to which participants with major depression
      differ from healthy comparison participants in the irregularities in affective
      information processing, characterized by deficits in facial expression
      recognition, intensity categorization, and reaction time to identifying
      emotionally salient and neutral information. Data on diagnoses, symptom severity,
      and affective information processing using a facial recognition task were
      collected from 66 participants, male and female between ages 18 and 54 years,
      grouped by major depressive disorder (N=37) or healthy non-psychiatric (N=29)
      status. Findings from MANCOVAs revealed that major depression was associated with
      a significantly longer reaction time to sad facial expressions compared with
      healthy status. Also, depressed participants demonstrated a negative bias towards
      interpreting neutral facial expressions as sad significantly more often than
      healthy participants. In turn, healthy participants interpreted neutral faces as
      happy significantly more often than depressed participants. No group differences
      were observed for facial expression recognition and intensity categorization. The
      observed effects suggest that depression has significant effects on the
      perception of the intensity of negative affective stimuli, delayed speed of
      processing sad affective information, and biases towards interpreting neutral
      faces as sad.

PMID- 18342955
TI  - Cloning, in vitro expression and bioactivity of duck interleukin-18.
AB  - The encoding sequence for duck IL-18 was obtained, using reverse transcription
      polymerase chain reaction, from mRNA harvested from Con A-stimulated Gushi (GS)
      duck splenic mononuclear cells. Recombinant duck IL-18 (rduIL-18) was produced in
      a prokaryotic expression system. In vitro bioactivity of rduIL-18 was determined
      in a lymphocyte proliferation assay and in vivo bioactivity of rduIL-18 was
      assessed by addition to a vaccine. Monoclonal antibody (mAb) and polyclonal
      antibodies (pAbs) specific for rduIL-18 were generated and subsequently
      characterized by ELISA, Western blot and neutralizing assays. Sequence analysis
      of GS duck IL-18 demonstrated an open reading frame (ORF) of 603 base pairs
      encoding for a 200 amino acid precursor protein. The duck encoding sequence
      shares 85.3% similarity to the chicken equivalent, at the nucleotide level. A His
      duIL-18 fusion protein was recognized in Western blot by mAbs against duck and
      chicken IL-18 (chIL-18), but not by mAb against human IL-18. Recombinant duIL-18
      induced in vitro proliferation of Con A-stimulated duck splenocytes and enhanced
      the immune response of ducks vaccinated with an inactivated oil emulsion vaccine
      against avian influenza virus. PAb and mAb 5B2 against rduIL-18 had neutralizing
      ability, inhibiting the biological activities of both recombinant duIL-18 and
      endogenous duIL-18. The results indicate that rduIL-18 has the potential to be
      used as an immunoadjuvant, and the mAb against rduIL-18 further facilitates basic
      immunobiological studies of the role of IL-18 in the avian immune system.

PMID- 18342956
TI  - Mast cell mediated inflammatory response in chickens after infection with very
      virulent infectious bursal disease virus.
AB  - The potential role of the mast cells in the invasion of very virulent infectious
      bursal disease virus (vvIBDV) is unknown. We evaluated mast cell activity and
      tryptase production after vvIBDV infection in special pathogen-free (SPF)
      chickens using cytochemistry and immunohistochemistry analyses. The results were
      as follows: (1) severe histologic lesions were observed in the thymus, spleen,
      cloacal bursa, liver, kidney and other tissues. vvIBDV viral antigens were
      detected and presented extensively in the parenchymatous organs, in particular,
      the cloacal bursa, liver, kidney, thymus, spleen and pancreas. (2) In the vvIBDV
      infected group, the mast cell population increased markedly in the liver, kidney,
      thymus, glandular stomach, spleen and cloacal bursa on days 1, 2 and 3 after
      vvIBDV infection (p<0.05). However, very few mast cells were observed in those
      same tissues in the controls, especially in the bursa of Fabricius. (3) Tryptase,
      a marker for activated mast cells, has a positive correlation with mast cell
      distribution. The mast cells identified in the tissues were likely to be
      activated since they were associated with cell degranulation and the presence of
      tryptase. Furthermore, the co-localization of mast cells, and presence of vvIBDV
      antigens suggests that the mast cells were activated by vvIBDV infection. Our
      results also suggest that tryptase may contribute to the inflammation of acute
      IBD induced by vvIBDV infection. Our research contributes to the further
      understanding of inflammatory response mechanisms and the contribution of mast
      cell activity to this process.

PMID- 18342957
TI  - Increased depressive behaviour in females and heightened corticosterone release
      in males to swim stress after adolescent social stress in rats.
AB  - We previously reported that males undergoing chronic social stress (SS) (daily 1h
      isolation and new cage partner on days 30-45 of age) in adolescence habituated
      (decreased corticosterone release) to the homotypic stressor, but females did
      not. Here, we report that adolescent males exposed to chronic social stress had
      potentiated corticosterone release to a heterotypic stressor (15 min of swim
      stress) compared to acutely stressed and control males. The three groups of males
      did not differ in depressive-like behaviour (time spent immobile) during the swim
      stress. Corticosterone release in socially stressed females was elevated 45 min
      after the swim stress compared to acutely stressed and control females, and
      socially stressed females exhibited more depressive behaviour (longer durations
      of immobility and shorter durations of climbing) than the other females during
      the swim stress. Separate groups of rats were tested as adults several weeks
      after the social stress, and there were no group differences in corticosterone
      release after the swim stress. The only group difference in behaviour among the
      adults was more time spent climbing in socially stressed males than in controls.
      Thus, there are sex-specific effects of social stress in adolescence on endocrine
      responses and depressive behaviour to a heterotypic stressor, but, unlike for
      anxiety, substantial recovery is evident in adulthood in the absence of
      intervening stress exposures.

PMID- 18342958
TI  - Nitric oxide involvement and neural substrates of the conditioned and innate fear
      as evaluated in the T-maze test in rats.
AB  - The L-arginine/nitric oxide (NO) pathways are widely distributed in the central
      nervous system (CNS) and have been implicated in the modulation of anxiety. The
      elevated plus-maze (ETM) is an animal test pharmacologically validated for the
      study of experimental anxiety in rats, designed to evaluate inhibitory avoidance
      (AVOID) learning and one-way escape (ESC) from open arms, thought to represent
      learned (conditioned) and innate (unconditioned) fear, respectively. The aim of
      the present study was to evaluate the effect of prior treatment with the NO
      synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on both AVOID
      and ESC behavior of rats in the ETM, when applied to different cerebral regions
      associated with defensive behaviors. Central treatment with L-NAME (50, 100, 400
      and 800 nmol) did not impair the AVOID response through the trials and had no
      effect on the ESC behavior. Nevertheless, animals treated with L-NAME at 200 nmol
      into the lateral ventricle (LV), basolateral amygdala (BLA), dorsolateral
      periaqueductal gray (dlPAG) matter, lateral septal nucleus (LSN), but not in the
      bed nucleus of stria terminalis (BNST), displayed impaired AVOID2 in comparison
      to the control group. Thus, our results suggest that NO may underlie learned fear
      in the ETM via BLA, dlPAG and LSN, but not BNST. These results are compatible
      with the proposal that NO exerts a positive modulatory role on defensive
      reactions in rats, exerting among them an anxiogenic-like effect as evaluated in
      rats submitted to ETM.

PMID- 18342959
TI  - Cadmium inhibits neurogenesis in zebrafish embryonic brain development.
AB  - Cadmium is a non-essential heavy metal found abundantly in the environment.
      Children of women exposed to cadmium during pregnancy display lower motor and
      perceptual abilities. High cadmium body burden in children is also related to
      impaired intelligence and lowered school achievement. However, little is known
      about the molecular and cellular basis of developmental neurotoxicity in the
      sensitive early life stages of animals. In this study, we explore neurological
      deficits caused by cadmium during early embryonic stages in zebrafish by
      examining regionalization of the neural tube, pattern formation and cell fate
      determination, commitment of proneural genes and induction of neurogenesis. We
      show that cadmium-treated embryos developed a smaller head with unclear
      boundaries between the brain subdivisions, particularly in the mid-hindbrain
      region. Embryos display normal anterior to posterior regionalization; however,
      the commitment of neural progenitor cells was affected by cadmium. We observe
      prominent reductions in the expression of several proneuronal genes including
      ngn1 in cell clusters, zash1a in the developing optic tectum, and zash1b in the
      telencephalon and tectum. Cadmium-treated embryos also have fewer differentiated
      neurons and glia in the facial sensory ganglia as indicated by decreased zn-12
      expression. Also, a lower transcription level of neurogenic genes, ngn1 and
      neuroD, is observed in neurons. Our data suggest that cadmium-induced
      neurotoxicity can be caused by impaired neurogenesis, resulting in markedly
      reduced neuronal differentiation and axonogenesis.

PMID- 18342960
TI  - Frequency, predictors and outcome of stent fracture after sirolimus-eluting stent
      implantation.
AB  - BACKGROUND: Recently, stent fracture (SF) of sirolimus-eluting stents (SES) has
      been shown to be associated with an increased risk of in-stent restenosis. We
      sought to evaluate the incidence, predictors and clinical outcome of SF after SES
      implantation in comparable unselected lesions. METHODS: A total of 430 lesions of
      382 patients treated with SES were analyzed. SF was defined as single or multiple
      stent strut fracture as well as complete separation of stent segments. RESULTS:
      At follow-up, SF was identified in 33 of 430 lesions (7.7%). In lesions with SF,
      the in-stent restenosis was observed more frequently than non-SF lesions (15.2%
      vs. 4.0%, P=0.004). At 450 days, however, the cumulative rate of major cardiac
      events was not significantly different between lesions with and without SF (9.1%
      vs. 7.1%, P=0.722). The risk of SF was independently associated with total stent
      length (OR 2.22; 95% CI, 1.25 to 3.95; P=0.007), the change in the angulation of
      the lesion after stenting (OR 1.55; 95% CI, 1.07 to 2.25; P=0.020), and the right
      coronary artery lesions (OR 3.26; 95% CI, 1.18 to 8.96; P=0.022). CONCLUSIONS:
      The occurrence of SF after SES implantation, was found to be relatively common in
      the particular population, however, did not lead to an increased risk of adverse
      cardiac events at 450 days, despite a higher incidence of in-stent restenosis.

PMID- 18342961
TI  - A successful implantation of a dual-chambers cardioverter defibrillator for a
      patient with severe tortuous persistent left superior vena cava.
AB  - We report a case of successful implantation of a dual-chambers transvenous
      cardioverter defibrillator for a dilated cardiomyopathy patient with severe
      tortuous persistent left superior vena cava and a very small innominate vein.
      After confirming the presence of a right superior vena cava, a dilated sheath was
      advanced into the narrow innominate vein to increase the lumen of innominate
      vein. The active atrial and ventricular leads were successfully inserted into
      right atrium and right ventricle through innominate bridge by the support of
      steerable long sheaths.

PMID- 18342962
TI  - The mortality cost to smokers.
AB  - This article estimates the mortality cost of smoking using the first labor market
      estimates of the value of statistical life by smoking status. The value of
      statistical life is $7 million for both smokers and nonsmokers. Using this value
      in conjunction with the increase in the mortality risk over the life cycle due to
      smoking, the value of statistical life by age and gender, and information on the
      number of packs smoked over the life cycle, the private mortality cost of smoking
      is $222 per pack for men and $94 per pack for women in $2006, based on a 3%
      discount rate. At discount rates of 15% or more, the cost decreases to under $25
      per pack.

PMID- 18342963
TI  - Can insurance increase financial risk? The curious case of health insurance in
      China.
AB  - We analyze the effect of insurance on the probability of an individual incurring
      'high' annual health expenses using data from three household surveys. All come
      from China, a country where providers are paid fee-for-service according to a
      schedule that encourages the overprovision of high-tech care and who are only
      lightly regulated. We define annual spending as 'high' if it exceeds a threshold
      of local average income and as 'catastrophic' if it exceeds a threshold of the
      household's own per capita income. Our estimates allow for different thresholds
      and for the possible endogeneity of health insurance (we use instrumental
      variables and fixed effects). Our main results suggest that in all three surveys
      health insurance increases the risk of high and catastrophic spending. Further
      analysis suggests that this is due to insurance encouraging people to seek care
      when sick and to seek care from higher-level providers.

PMID- 18342964
TI  - Randomized clinical trial on 7-days-a-week postoperative radiotherapy for high
      risk squamous cell head and neck cancer.
AB  - PURPOSE: To evaluate the normal tissue reactions and loco-regional control rates
      (LRC) in patients treated with 7-days-a-week postoperative continuous irradiation
      (p-CAIR) compared to conventionally fractionated 5-days-a-week postoperative
      radiotherapy (CF). MATERIALS/METHODS: Between 2001 and 2004, 279 patients with
      high-risk squamous cell cancer of the larynx (158 pts.) or cancer of the oral
      cavity/oropharynx (121 pts.) were enrolled. They were stratified according to the
      primary cancer site (larynx vs. others) and the treating center and randomized to
      receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 pts: CF) or 7-days
      a-week (139 pts: p-CAIR). RESULTS: The acute and late toxicity was considered
      acceptable, although the proportion of patients with confluent mucositis was
      higher in p-CAIR compared to CF (60.0 vs. 33.3%). The actuarial 3-year LRC were
      64 vs. 70% for CF and p-CAIR, respectively, p=0.32. A statistically significant
      improvement in 3-year LRC in p-CAIR arm appeared in a subset of the patients with
      cancer of the oropharynx/oral cavity (74% p-CAIR vs. 53% CF, p=0.02). By
      contrast, there was no improvement in LRC in a subset of the patients with cancer
      of the larynx (p=0.46). CONCLUSION: An improvement in LRC attributable to
      acceleration of postoperative radiotherapy appeared restricted to the patients
      with cancer of the oropharynx/oral cavity. In patients with cancer of the larynx
      acceleration of postoperative radiotherapy did not have any beneficial effect.

PMID- 18342965
TI  - A dose escalation study of hyperfractionated accelerated radiation delivered with
      integrated neck surgery (HARDWINS) for the management of advanced head and neck
      cancer.
AB  - BACKGROUND AND PURPOSE: To determine toxicity and outcome of radiation dose
      escalation with hyperfractionated accelerated radiation delivered with neck
      surgery (HARDWINS) for head and neck cancer. PATIENTS AND METHODS: Patients with
      stage III and IV squamous cell carcinoma of the oropharynx, hypopharynx or larynx
      were enrolled. Dose levels of 60, 62 and 64Gy were delivered with twice daily
      fractionation in 40 fractions over 4 weeks. Involved and at-risk nodal regions
      received microscopic dose (46.5-48Gy) with neck dissection for node positive
      patients 8 weeks after radiation. RESULTS: One hundred and sixty-nine patients
      were enrolled (60Gy n=22, 62Gy n=26, 64Gy n=121). No grade 4 acute toxicity was
      observed. Incidence of acute grade 3 toxicity was: skin (2%), larynx (6%),
      pharynx and esophagus (66%) and mucous membrane (75%). Feeding tube dependence
      was observed in 14% of patients receiving 64Gy. Overall survival, and relapse
      free rate at 5 years were 65% and 63%, respectively. Local, nodal and distant
      relapse free rates at 5 years were 77%, 94% and 81% (median follow-up 3.8 years).
      CONCLUSIONS: HARDWINS can be delivered without acute grade 4 toxicity but
      significant grade 3 acute toxicity. A significant proportion of the patients have
      prolonged swallowing dysfunction. Outcomes suggest this regimen represents an
      alternative to chemoradiation.

PMID- 18342966
TI  - Nutritional factors as predictors of response to radio-chemotherapy and survival
      in unresectable squamous head and neck carcinoma.
AB  - BACKGROUND AND PURPOSE: This study sought to evaluate nutritional prognostic
      factors before treatment in patients with unresectable head and neck cancer
      treated by concomitant radio-chemotherapy. METHODS AND MATERIALS: Seventy-two
      consecutive patients were treated. We studied the potential effects of CRP, Alb,
      preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response
      to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of
      potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier
      estimates, and curves were compared using the log-rank test. RESULTS: All
      biological nutritional factors were statistically correlated with the response to
      radio-chemotherapy. In multivariate analysis, only CRP (p=0.004) remained
      statistically significant. A statistical correlation was found between Alb and
      EFS in multivariate analysis (p=0.04). The factors influencing OS in univariate
      analysis were Alb (p=0.008), CRP (p=0.004), orosomucoid (p=0.01) and NRI
      (p=0.01), response to radio-chemotherapy (p<0.001) and staging (p=0.04). In
      multivariate analysis, only the response to radio-chemotherapy (p<0.001) remained
      significant. CONCLUSIONS: This study illustrates the prognostic value of
      nutritional status. CRP and Alb may be useful in the assessment of advanced head
      and neck cancer patients at diagnosis and for stratifying patients taking part in
      randomized trials.

PMID- 18342967
TI  - 18FDG-PET based radiation planning of mediastinal lymph nodes in limited disease
      small cell lung cancer changes radiotherapy fields: a planning study.
AB  - BACKGROUND AND PURPOSE: To investigate the influence of selective irradiation of
      18FDG-PET positive mediastinal nodes on radiation fields and normal tissue
      exposure in limited disease small cell lung cancer (LD-SCLC). MATERIAL AND
      METHODS: Twenty-one patients with LD-SCLC, of whom both CT and PET images were
      available, were studied. For each patient, two three-dimensional conformal
      treatment plans were made with selective irradiation of involved lymph nodes,
      based on CT and on PET, respectively. Changes in treatment plans as well as
      dosimetric factors associated with lung and esophageal toxicity were analyzed and
      compared. RESULTS: FDG-PET information changed the treatment field in 5 patients
      (24%). In 3 patients, this was due to a decrease and in 2 patients to an increase
      in the number of involved nodal areas. However, there were no significant
      differences in gross tumor volume (GTV), lung, and esophageal parameters between
      CT- and PET-based plans. CONCLUSIONS: Incorporating FDG-PET information in
      radiotherapy planning for patients with LD-SCLC changed the treatment plan in 24%
      of patients compared to CT. Both increases and decreases of the GTV were
      observed, theoretically leading to the avoidance of geographical miss or a
      decrease of radiation exposure of normal tissues, respectively. Based on these
      findings, a phase II trial, evaluating PET-scan based selective nodal
      irradiation, is ongoing in our department.

PMID- 18342968
TI  - Efficacy of novel hypoxic cell sensitiser doranidazole in the treatment of
      locally advanced pancreatic cancer: long-term results of a placebo-controlled
      randomised study.
AB  - Novel hypoxic cell radiosensitiser doranidazole was tested for unresectable
      pancreatic cancer administered at intraoperative radiotherapy. Short-term
      survival was not different. However, difference has been observed concerning 3
      year survival (doranidazole group vs. placebo; 23% vs. 0%, p=0.0192). This
      sensitiser might be effective in improving long-term survival for pancreatic
      cancer.

PMID- 18342969
TI  - Late tissue effects following radiotherapy and neoadjuvant hormone therapy of the
      prostate measured with quantitative magnetic resonance imaging.
AB  - BACKGROUND AND PURPOSE: To use quantitative MRI to detect changes in the vascular
      and MR relaxation characteristics of the prostate gland 1 year after external
      beam radiotherapy. MATERIALS AND METHODS: Twenty-one patients underwent MRI
      before and after external beam radiotherapy for prostatic adenocarcinoma. Tracer
      kinetics analysis was applied to data from regions of interest in prostate
      tumour, normal prostate peripheral zone and muscle to obtain estimates of blood
      flow, extravascular-extracellular volume, blood volume and capillary permeability
      surface area product. T(1) and T(2) were also measured in these regions. RESULTS:
      Significant changes (p<0.05) after radiotherapy were found in all three tissues
      examined. Tumour blood flow was 0.34 and 0.14 ml (ml tissue)(-1) min(-1) before
      and after treatment, respectively, and T(1) increased from 922 to 1,070 ms. In
      normal peripheral zone, extravascular-extracellular volume increased from 0.21 to
      0.52 ml (ml tissue)(-1), and T(2) decreased from 126 to 106 ms. In muscle, both
      permeability surface area product and T(2) rose, from 0.02 to 0.06 ml (ml
      tissue)(-1) min(-1) and from 50 to 56 ms, respectively. CONCLUSIONS: Quantitative
      MRI can be used to measure significant changes in both vascular and MR relaxation
      properties of the prostate and nearby muscle following treatment for prostate
      cancer using external beam radiotherapy.

PMID- 18342970
TI  - Directed evolution of transketolase substrate specificity towards an aliphatic
      aldehyde.
AB  - Mutants of transketolase (TK) with improved substrate specificity towards the non
      natural aliphatic aldehyde substrate propionaldehyde have been obtained by
      directed evolution. We used the same active-site targeted saturation mutagenesis
      libraries from which we previously identified mutants with improved activity
      towards glycolaldehyde, which is C2-hydroxylated like all natural TK substrates.
      Comparison of the new mutants to those obtained previously reveals distinctly
      different subsets of enzyme active-site mutations with either improved overall
      enzyme activity, or improved specificity towards either the C2-hydroxylated or
      non-natural aliphatic aldehyde substrate. While mutation of phylogenetically
      variant residues was found previously to yield improved enzyme activity on
      glycolaldehyde, we show here that these mutants in fact gave improved activity on
      both substrate types. In comparison, the new mutants were obtained at conserved
      residues which interact with the C2-hydroxyl group of natural substrates, and
      gave up to 5-fold improvement in specific activity and 64-fold improvement in
      specificity towards propionaldehyde relative to glycolaldehyde. This suggests
      that saturation mutagenesis can be more selectively guided for evolution towards
      either natural or non-natural substrates, using both structural and sequence
      information.

PMID- 18342971
TI  - Production and characterization of recombinant dengue virus type 4 envelope
      domain III protein.
AB  - Dengue fever, a mosquito-borne viral disease has become a major worldwide public
      health problem with a dramatic expansion in recent years. Cultivation process for
      production of recombinant dengue virus type 4 envelope domain III (rDen 4 EDIII)
      protein in Escherichia coli was developed for its diagnostic use as well as for
      further studies in immunoprophylaxis. The dissolved oxygen level was maintained
      at 20-30% of air saturation. The culture was induced with 1mM of isopropyl beta-d
      thiogalactoside when dry cell weight was 13.78 g l(-1) and cells were further
      grown for 4h to reach 17.31 g l(-1) of culture. The protein was overexpressed in
      the form of insoluble inclusion bodies. The rDen 4 EDIII protein was purified by
      affinity chromatography and analyzed by SDS-PAGE. The final yield of purified
      rDen 4 EDIII protein in this method was approximately 196 mg l(-1) of culture.
      The purified protein was recognized in Western blot analysis and enzyme-linked
      immunosorbent assay (ELISA) with dengue infected human serum samples. These
      results show that the product has the potential to be used for the diagnosis of
      dengue infection or for further studies in vaccine development. This production
      system may also be suitable for the high yield of other recombinant dengue
      proteins.

PMID- 18342972
TI  - A novel hydantoinase process using recombinant Escherichia coli cells with
      dihydropyrimidinase and L-N-carbamoylase activities as biocatalyst for the
      production of L-homophenylalanine.
AB  - A dihydropyrimidinase gene (pydB) was cloned from the moderate thermophilic
      Brevibacillus agri NCHU1002 and expressed in Escherichia coli. The purified
      dihydropyrimidinase exhibited strict d-enantioselectivity for D,L-p
      hydroxyphenylhydantoin and D,L-5-[2-(methylthio)ethyl]hydantoin, and non
      enantiospecificity for D,L-homophenylalanylhydantoin (D,L-HPAH). The hydrolytic
      activity of PydB was enhanced notably by Mn2+, with a maximal activity at 60
      degrees C and pH 8.0. This enzyme was completely thermostable at 50 degrees C for
      20 days. A whole cell biocatalyst for the production of L-homophenylalanine (L
      HPA) from D,L-HPAH by coexpression of the pydB gene and a thermostable L-N
      carbamoylase gene from Bacillus kaustophilus CCRC11223 in E. coli JM109 was
      developed. The expression levels of dihydropyrimidinase and L-N-carbamoylase in
      the recombinant E. coli cells were estimated to be about 20% of the respective
      total soluble proteins. When 1% (w/v) isopropyl-beta-D-thiogalactopyranoside
      induced cells were used as biocatalysts, a conversion yield of 49% for L-HPA with
      more than 99% ee could be reached in 16 h at pH 7.0 from 10mM D,L-HPAH. The cells
      can be reused for at least eight cycles at a conversion yield of more than 43%.
      Our results revealed that coexpression of pydB and lnc in E. coli might be a
      potential biocatalyst for L-HPA production.

PMID- 18342973
TI  - Characterization of cross-reactive and serotype-specific epitopes on the
      nucleocapsid proteins of hantaviruses.
AB  - The hantavirus nucleocapsid (N) protein fulfills several key roles in virus
      replication and assembly and is the major antigen in humoral immune responses in
      humans and mice. Here we report on epitopes involved in serotype-specific and
      cross-reactive recognition of the N proteins of hantaviruses using monoclonal
      antibodies (mAbs) against the N proteins of Andes virus (ANDV) and Sin Nombre
      virus (SNV). The mAbs define at least twelve different epitopic patterns which
      span eight sequences, including amino acids 17-59, 66-78, 79-91, 157-169, 222
      234, 244-263, 274-286 and 326-338 on the SNV and ANDV N proteins. Studies on the
      cross-reactivity of these mAbs with different hantavirus N proteins indicated
      that epitopes located within amino acids 244-286 are related to serotype
      specificity. We analyzed further the location of epitopes with available three
      dimensional structure information including the N-terminal coiled-coil and
      derived exposed and hidden residues of these epitopes. The generated recombinant
      N proteins and the characterized mAbs are functional tools being now available
      for hantavirus diagnostics and replication studies.

PMID- 18342974
TI  - The potential of lipid- and polymer-based drug delivery carriers for eradicating
      biofilm consortia on device-related nosocomial infections.
AB  - Microbial biofilms are microcosm attaching irreversibly to abiotic or biotic
      surfaces and they are promulgated as congregate of single or multiple
      populations. The potential of lipid- and polymer-based drug delivery carriers for
      eradicating biofilm consortia on device-related nosocomial infections is explored
      in this review. Liposomes-loaded with antimicrobial agents could effectively be
      applied as anti-biofilm coating to reduce microbial adhesion/colonisation onto
      medical devices and as drug delivery carriers to biofilm interfaces and in
      intracellular infection. Many polymer-based carrier systems have also been
      proposed, including those based on biodegradable polymers such as poly(lactide co
      glycolide) as well as fibrous scaffolds and thermoreversible hydrogels and
      surface (properties) modified polymeric catheter materials such as antimicrobial,
      antiseptic or metallic substances-coated polymeric materials. Their contribution
      to the prevention/resolution of infection is reviewed.

PMID- 18342975
TI  - Pulsatile release of biomolecules from polydimethylsiloxane (PDMS) chips with
      hydrolytically degradable seals.
AB  - We demonstrate, for the first time, a robust novel polydimethylsiloxane (PDMS)
      chip that can provide controlled pulsatile release of DNA based molecules,
      proteins and oligonucleotides without external stimuli or triggers. The PDMS chip
      with arrays of wells was constructed by replica molding. Poly(lactic acid-co
      glycolic acid) (PLGA) polymer films of varying composition and thickness were
      used as seals to the wells. The composition, molecular weight and thickness of
      the PLGA films were all parameters used to control the degradation rate of the
      seals and therefore the release profiles. Degradation of the films followed the
      PLGA composition order of 50:50 PLGA>75:25 PLGA>85:15 PLGA at all time-points
      beyond week 1. Scanning electron microscopy images showed that films were
      initially smooth, became porous and ruptured as the osmotic pressure pushed the
      degrading PLGA film outwards. Pulsatile release of DNA was controlled by the
      composition and thickness of the PLGA used to seal the well. Transfection
      experiments in a model Human Embryonic Kidney 293 (HEK293) cell line showed that
      plasmid DNA loaded in the wells was functional after pulsatile release in
      comparison to control plasmid DNA at all time-points. Thicker films degraded
      faster than thinner films and could be used to fine-tune the release of DNA over
      day length periods. Finally the PDMS chip was shown to provide repeated
      sequential release of CpG oligonucleotides and a model antigen, Ovalbumin (OVA),
      indicating significant potential for this device for vaccinations or applications
      that require defined complex release patterns of a variety of chemicals, drugs
      and biomolecules.

PMID- 18342976
TI  - A fatigue questionnaire (QFES) for child athletes: a four-year follow-up study in
      young skiers.
AB  - BACKGROUND: The use of a fatigue monitoring questionnaire is an increasingly
      widespread practice in sports medicine. OBJECTIVE: To evaluate variations in the
      QFES fatigue questionnaire score according to periods of rest, training or
      competition. METHODS: Sixty-six skiers (either alpine or cross-country skiers,
      aged between 11 and 14 years and training for between 12 and 18 hours per week)
      filled out a total of 400 fatigue questionnaires over a four-year follow-up
      period. RESULTS: Our analysis of the QFES fatigue scores showed that only a small
      proportion of the skiers (5.25%, on average) exceeded the fatigue alert threshold
      at some point during the longitudinal follow-up; periods of competition
      correspond to rising fatigue scores, in comparison with the beginning of season
      and girls always have higher scores than boys (25.32+/-0.90 versus 20.46+/-0.91,
      respectively; p<0.0002). In contrast, there was no correlation between fatigue
      levels and the type of skiing discipline practiced. CONCLUSION: Our main results
      show that the QFES fatigue questionnaire is a sensitive tool for tracking down
      particular periods of fatigue (competition, intense training). Even though the
      mechanism of fatigue is still not fully understood (highlighting the complexity
      of this syndrome), the systematic use of a fatigue questionnaire when monitoring
      children performing competitive sport and high volumes of training confirms the
      possible preventive role of this type of tool.

PMID- 18342977
TI  - [Development and test of a new plantar pressure control device for foot
      unloading].
AB  - OBJECTIVE: To validate a new plantar pressure control device able to detect
      excessive plantar pressure on-line and to improve the subject's awareness of the
      gait pattern in order to correct and optimize the load distribution patterns. The
      aim of this study was to verify the feasibility of a deliberate and partial
      unload of the first metatarsal head. MATERIAL AND METHOD: Eight healthy subjects
      were equipped with the plantar pressure sensors integrated in customized insoles.
      They were told to unload the first metatarsal head of the right foot by 5%.
      During the trials, the auditory and visual signals inform the subject of an
      excessive, insufficient or correct unload. RESULTS: Five subjects over eight
      succeeding in modifying significantly their gait pattern and in unloading by 5%
      the first metatarsal head. The unload is effective in 70.7% of the trials.
      However, the subjects were spontaneously inclined to reduce peak pressure under
      the first metatarsal head beyond the critical peak plantar pressure threshold
      (48.2% of the trials). DISCUSSION - CONCLUSION: The results showed the
      feasibility of a partial and deliberate foot unloading in using biofeedback
      device but emphasized the subject's difficulty to control a discriminated and
      accurate unload of the first metatarsal head. That points out the necessity of
      learning period. The baropodometric biofeedback rehabilitation focuses on the
      subject's capacities to modify its own locomotor pattern. It would be used as
      primary and secondary prevention means of diabetic foot ulceration.

PMID- 18342978
TI  - Detailed glomerular ultrastructure in Japanese type 2 diabetic patients by the
      quick-freezing and deep-etching method.
AB  - Mesangial expansion and glomerular basement membrane (GBM) thickening did not
      correlate with urinary albumin excretion (UAE) in type 2 diabetic patients in our
      previous studies; therefore, it was necessary to elucidate more detailed
      ultrastructural changes in the early stages of diabetic nephropathy (DN) in type
      2 diabetic patients. The quick-freezing and deep-etching (QF-DE) method allows us
      to examine three-dimensional ultrastructures of human renal glomeruli in vivo at
      high resolution. The QF-DE method was applied to six type 2 diabetic patients
      without definable renal diseases other than DN. Four patients were
      normoalbuminuric (NA) and the other two were microalbuminuria (MA). Three control
      specimens were the normal parts from nephrectomies due to renal cell carcinomas.
      Electron microscopic morphometric analyses provided quantitative glomerular
      structural changes. Replica membranes were prepared by the QF-DE method, and
      diameters of mesh structures at the GBM and mesangial matrix (MM) were measured
      on electron micrographs as previously described. By the QF-DE method, both the
      GBM middle layer and MM were composed of polygonal meshwork structures. The mesh
      pores of the GBM and MM were more enlarged and irregular in shape in NA diabetic
      patients than those of the controls, and these ultrastructural changes became
      more obvious in MA patients. The mesh diameters of the GBM and MM in the diabetic
      patients were also larger than those of the controls. Such a mesh diameter of the
      GBM was well correlated with the amount of UAE, while the mesh diameter of MM
      showed a slight correlation with UAE. Although there were small number of
      subjects in the present study, the detailed ultrastructural changes in NA and MA
      type 2 diabetic patients, which had not been disclosed by conventional electron
      microscopy, were revealed by the QF-DE method. Increased mesh diameters of GBM
      might be related with the increase of UAE.

PMID- 18342979
TI  - Recent Australian suicide trends for males and females at the national level: has
      the rate of decline differed?
AB  - OBJECTIVES: In keeping with international public health policy development,
      suicide prevention in Australia has received increasing attention. The mid to
      late 1990s saw the introduction of a range of co-ordinated national prevention
      programmes. Since 1997, suicides have decreased, but the comparative rates of
      decline for males and females have not been well studied at the national level.
      METHODS: Standardised suicide rates were calculated for males and females, using
      data from 1997 to 2005. Linear models (ordinary least squares) were used to
      calculate rates of decline, with trends compared for males and females. RESULTS:
      Male suicides appear to have fallen more rapidly than female suicides.
      CONCLUSIONS: Australian males, an 'at risk' demographic, appear to be
      experiencing benefits from the existence of current national suicide prevention
      strategies and related social changes. It is recommended that greater
      consideration be given to researching risk factors such as intimate partner
      violence, sexual abuse, and substance dependence, for Australian female suicide.

PMID- 18342980
TI  - Public purchasers contracting external primary care providers in Central America
      for better responsiveness, efficiency of health care and public governance:
      issues and challenges.
AB  - Several national health systems in Latin America initiated health reforms to
      counter widespread criticisms of low equity and efficiency. For public purchasing
      agencies, these reforms often consisted in contracting external providers for
      primary care provision. This paper intends to clarify both the complex and
      intertwined issues characterizing such contracting as well as health system
      performances within the context of four Central American countries. It results
      from a European Commission financed project lead between 2002 and 2005, involving
      participants from Costa Rica, Guatemala, Nicaragua, Salvador, United Kingdom,
      Netherlands and Belgium, whose aim was to promote exchanges between these
      participants. The findings presented in this paper are the results of a two stage
      process: (a) the design of an initial analytical framework, built upon findings
      from the literature, interlinking characteristics of contractual relation with
      health systems performances criteria and (b) the use of that framework in four
      case studies to identify cross-cutting issues. This paper reinforces two pivotal
      findings: (a) contracting requires not only technical, but also political choices
      and (b) it cannot be considered as a mechanical process. The unpredictability of
      its evolution requires a flexible and reactive approach. This should be better
      assimilated by national and international organizations involved in health
      services provision, so as to progressively come out of dogmatic approaches in
      deciding to initiate contractual relation with external providers for primary
      care provision.

PMID- 18342981
TI  - Biofidelic child head FE model to simulate real world trauma.
AB  - Biomechanics of human head has been widely studied since several decades. At a
      mechanical level, the use of engineering allowed investigating injury mechanisms
      developing numerical models of adult head. For children, the problem is more
      difficult and evaluating child injury mechanisms using data obtained from scaling
      adult injury criteria does not account for differences in morphology and
      structure between adults and children. During growth, child head undergoes
      different modifications in morphology and structure. The present paper compares
      the anthropometry and numerical simulations of a child head model based on
      medical CT scans to a child head model developed by scaling an adult head model
      using the method proposed by Mertz [H.J. Mertz, A procedure for normalizing
      impact response data, SAE paper 840884, 1984]. These analysis point out
      significant differences showing that scaling down an adult head to obtain a child
      head does not appear relevant. Biofidelic and specific child geometry is needed
      to investigate child injury mechanisms.

PMID- 18342982
TI  - Phase II trial of weekly docetaxel and gemcitabine for previously untreated,
      advanced non-small cell lung cancer.
AB  - Docetaxel and gemcitabine combination chemotherapy has been reported to be active
      against non-small cell lung cancer (NSCLC) and myelosuppression is the most
      common dose-limiting toxicity. This prospective phase II study was designed to
      test the hypothesis that better tolerance and increased dose intensity might be
      achieved if patients are treated with weekly administration schedule. Thirty-five
      patients with stage IIIB/IV NSCLC and a performance status 0-2 received first
      line chemotherapy with docetaxel 35mg/m2 and gemcitabine 600mg/m2 on days 1, 8
      and 15. Treatment was repeated every 4 weeks, for up to 4 cycles. In total, 85
      chemotherapy cycles were given (median, 2; range, 1-4). Other than the completion
      of all 4 planned cycles (n=6), the main reasons for treatment discontinuation
      were toxicity (n=15) and progressive disease (n=14). The most frequently
      encountered toxic effects were anemia (52% of patients), nausea and vomiting
      (60%), fatigue (71%) and anorexia (57%). One patient died of bilateral
      pneumonitis, which developed shortly after the administration of second cycle.
      Disease control (objective response and stable disease) in the intent-to-treat
      (ITT) population was achieved in 60% of patients and the overall response rate
      was 29% (95% CI, 14-44%). With a median follow-up duration of 13 months, the
      median progression-free survival and overall survival were 2.8 (95% CI, 0.7-4.8)
      months and 10.6 (95% CI, 7.0-14.3) months, respectively. In conclusion, weekly
      schedule of docetaxel and gemcitabine has modest activity with acceptable
      toxicity profile in advanced NSCLC, but as high frequency of early
      discontinuation occurred does not merit further study with the present regimen.

PMID- 18342983
TI  - Integrins and the activation of latent transforming growth factor beta1 - an
      intimate relationship.
AB  - Integrins are crucial for the ability of cells to sense mechanical perturbations
      and to transmit intracellular stress to their environment. We here review the
      more recently discovered role of integrins in activating the pleiotrophic
      cytokine transforming growth factor beta 1 (TGF-beta1). TGF-beta1 controls tissue
      homeostasis in embryonic and normal adult tissues and contributes to the
      development of fibrosis, cancer, autoimmune and vascular diseases when being mis
      regulated. In most of these conditions, active TGF-beta1 is generated by
      dissociation from a large latent protein complex that sequesters latent TGF-beta1
      in the extracellular matrix (ECM). Two main models are proposed how integrins
      contribute to latent TGF-beta1 activation: (1) In a protease-dependent mechanism,
      integrins alphavbeta8 and alphavbeta3 are suggested to simultaneously bind the
      latent TGF-beta1 complex and proteinases. This close vicinity at the cell surface
      improves enzymatic cleavage of the latent complex to release active TGF-beta1.
      (2) Integrins alphavbeta3, alphavbeta5, alphavbeta6, and alphavbeta8 appear to
      change the conformation of the latent TGF-beta1 complex by transmitting cell
      traction forces. This action requires association of the latent complex with a
      mechanically resistant ECM and is independent from proteolysis. Understanding
      that different integrins use different mechanisms to activate latent TGF-beta1
      opens new possibilities to develop cell-specific therapeutic strategies for TGF
      beta1-induced pathologies.

PMID- 18342984
TI  - Interplay between TRP channels and the cytoskeleton in health and disease.
AB  - Transient receptor potential (TRP) channels are a family of cation channels that
      play a key role in ion homeostasis and cell volume regulation. In addition, TRP
      channels are considered universal integrators of sensory information required for
      taste, vision, hearing, touch, temperature, and the detection of mechanical
      force. Seminal investigations exploring the molecular mechanisms of
      phototransduction in Drosophila have demonstrated that TRP channels operate
      within macromolecular complexes closely associated with the cytoskeleton. More
      recent evidence shows that mammalian TRP channels similarly connect to the
      cytoskeleton to affect cytoskeletal organization and cell adhesion via ion
      transport-dependent and -independent mechanisms. In this review, we discuss new
      insights into the interplay between TRP channels and the cytoskeleton and provide
      recent examples of such interactions in different physiological systems.

PMID- 18342985
TI  - Genetic variability of nitrogen accumulation during vegetative development and
      remobilization during the forcing process in witloof chicory tuberized root
      (Cichorium intybus L.).
AB  - A better knowledge of genetic variability of traits related to nitrogen use
      efficiency (NUE) is a potential strategy to optimize N fertilization and to
      reduce environmental pollution without decreasing marketable yield and quality.
      To this aim, in this study, 13 cultivars of witloof chicory were compared with
      three reference cultivars known for their adaptation to low, intermediate and
      high N availability in the field during the vegetative phase of development.
      Pertinent criteria used for this study were determined by a thorough comparison
      of nitrogen reserve accumulation in tuberized roots during vegetative development
      and mobilization during the forcing process in the three reference cultivars.
      Cluster analysis allowed us to sort the cultivars into four main groups we named
      G1, G2, G3 and G4. Cultivars of group G4, better adapted to soils with high
      nitrogen contents (N-demanding cultivars), showed higher total N, nitrate, total
      amino acids (AA), glutamine contents and lower total N and AA mobilization for
      chicon growth than did cultivars of group G1, adapted to soils with low nitrogen
      content (N-sensitive cultivars). An intermediate behavior was exhibited by
      cultivars of groups G2 and G3, characterized as N tolerant. It is proposed that
      either chicory growers or breeders may take advantage of the genetic variability
      revealed in the present study to gain flexibility in choosing the right cultivar
      for the type of soil available (N-rich soil vs N-poor soil) or to adapt the level
      of N fertilization to the type of cultivar (N-demanding vs N-sensitive) in order
      to target the highest NUE for the best chicon yield and trade quality.

PMID- 18342986
TI  - Modification of vacuolar proton pumps in cucumber roots under salt stress.
AB  - The time-dependent effect of 50mM NaCl on the activities of two tonoplast proton
      pumps was investigated in Cucumis sativus L. var. Krak root cells. Distinct
      activity profiles for vacuolar proton transporting ATPase (V-ATPase) (EC
      3.6.3.14) and vacuolar proton transporting pyrophosphatase (V-PPase) (EC 3.6.1.1)
      under salinity are presented. ATP-dependent proton transport and ATP hydrolysis
      increased after 24h of NaCl exposure, and then decreased in roots stressed with
      NaCl for 4 and 8d. Both PP(i)-driven H(+) transport and PP(i) hydrolysis were
      clearly inhibited by NaCl at all times examined. It was demonstrated that changes
      in enzyme activities were not due to the salt action on the expression of
      encoding genes. The levels of specific transcripts for subunit A of V-ATPase
      (CsVHA-A), subunit c of V-ATPase (CsVHA-c) and V-PPase (CsVP) were similar in
      cucumber roots untreated (control) and treated with salt. Such results suggest
      that alterations of proton pump activities under salinity are rather due to the
      post-translational alterations induced by NaCl.

PMID- 18342987
TI  - Low temperature and defoliation affect fructan-metabolizing enzymes in different
      regions of the rhizophores of Vernonia herbacea.
AB  - In addition to the storage function, fructans in Asteraceae from floras with
      seasonal growth have been associated with drought and freezing tolerance.
      Vernonia herbacea, native of the Brazilian Cerrado, bears underground reserve
      organs, rhizophores, accumulating inulin-type fructans. The rhizophore is a
      cauline branched system with positive geotropic growth, with the apex (distal
      region) presenting younger tissues; sprouting of new shoots occurs by development
      of buds located on the opposite end (proximal region). Plants induced to
      sprouting by excision of the aerial organs present increased 1-fructan
      exohydrolase (1-FEH) activity in the proximal region, while plants at the
      vegetative stage present high 1-sucrose:sucrose fructosyltransferase (1-SST) in
      the distal region. The aim of the present study was to analyze how low
      temperature (5 degrees C) could affect fructan-metabolizing enzymes and fructan
      composition in the different regions of the rhizophores of intact and excised
      plants. 1-SST and 1-fructan:fructan fructosyltransferase (1-FFT) were higher in
      the distal region decreasing towards the proximal region in intact plants at the
      vegetative phase, and were drastically diminished when cold and/or excision were
      imposed. In contrast, 1-FEH increased in the proximal region of treated plants,
      mainly in excised plants subjected to cold. The ratio fructo-oligo to fructo
      polysaccharides was significantly higher in plants exposed to low temperature
      (1.17 in intact plants and 1.64 in excised plants) than in plants exposed to
      natural temperature conditions (0.84 in intact vegetative plants and 0.58 in
      excised plants), suggesting that oligosaccharides are involved in the tolerance
      of plants to low temperature via 1-FEH, in addition to 1-FFT. Principal component
      analysis indicated different response mechanisms in fructan metabolism under
      defoliation and low temperature, which could be interpreted as part of the
      strategies to undergo unfavorable environmental conditions prevailing in the
      Cerrado during winter.

PMID- 18342989
TI  - Resisting temptation: effects of exposure to a forbidden food on eating
      behaviour.
AB  - The study tests existing evidence on the paradoxical effects of exposure to a
      forbidden snack. Sixty-eight females were assigned randomly to one of two
      conditions: a temptation group, who were given the instruction to abstain from a
      favourite snack for 24h while being exposed to it, or a control group, who were
      given no specific instructions. A further distinction was made between high
      restraint/high-disinhibition (n=21), high-restraint/low-disinhibition (n=20) and
      low-restraint participants (n=27) based on DEBQ subscale scores. After exposure
      to the foods, all participants were given free access to the food. Participants
      ate more of the snack after abstinence with exposure. The high-restraint/high
      disinhibition group in particular displayed a substantial disinhibition effect.
      Results indicate that prohibition with exposure may backfire and increase the
      risk of loss of control over eating behaviour, particularly in at-risk groups of
      disinhibited restrained eaters.

PMID- 18342988
TI  - Psychometric properties of a new questionnaire to assess eating in the absence of
      hunger in children and adolescents.
AB  - BACKGROUND: Eating in the absence of hunger (EAH), studied in the context of
      laboratory paradigms, has been associated with obesity and is predictive of
      excess weight gain in children. However, no easily administered questionnaire
      exists to assess for EAH in children. OBJECTIVE: We developed an Eating in the
      Absence of Hunger Questionnaire to be administered to children and adolescents
      (EAH-C) and examined psychometric properties of the measure. DESIGN: Two-hundred
      and twenty-six obese (BMI > or = 95th percentile for age and sex, n=73) and non
      obese (BMI<95th percentile, n=153) youth (mean age+/-S.D., 14.4+/-2.5 y)
      completed the EAH-C and measures of loss of control and emotional eating, and
      general psychopathology. Temporal stability was assessed in a subset of
      participants. RESULTS: Factor analysis generated three subscales for the EAH-C:
      Negative Affect, External Eating, and Fatigue/Boredom. Internal consistency for
      all subscales was established (Cronbach's alphas: 0.80-0.88). The EAH-C subscales
      had good convergent validity with emotional eating and loss of control episodes
      (p's<0.01). Obese children reported higher Negative Affect subscale scores than
      non-obese children (p</=0.05). All three subscales were positively correlated
      with measures of general psychopathology. Intra-class correlation coefficients
      revealed temporal stability for all subscales (ranging from 0.65 to 0.70,
      p's<0.01). We conclude that the EAH-C had internally consistent subscales with
      good convergent validity and temporal stability, but may have limited
      discriminant validity. Further investigations examining the EAH-C in relation to
      laboratory feeding studies are required to determine whether reported EAH is
      related to actual energy intake or to the development of excess weight gain.

PMID- 18342990
TI  - Body dissatisfaction mediates the association between body mass index and risky
      weight control behaviors among White and Native American adolescent girls.
AB  - The developmental path leading to eating disorders among adolescent girls often
      proceeds from increasing body size, to increasing body dissatisfaction, to
      increasing eating disorder (ED) risk. To determine whether body dissatisfaction
      (BD) mediates the association between body size and risky weight control
      behaviors, we examined data from White (n=709) and Native American (n=253) girls,
      who differ substantially in terms of average body mass and reported weight
      control behaviors. Measures of BD included weight, shape, and appearance
      concerns. Measures of ED risk included dieting, exercising to control weight,
      binge eating, and vomiting. Results showed body dissatisfaction was a highly
      significant mediator of the relationship between body mass index (BMI) and ED
      risk for both ethnic groups; although, BD did not mediate the association between
      BMI and binge eating for either group. BD is apparently an important mediator of
      the association between body size and some, but not all, risky weight control
      behaviors.

PMID- 18342991
TI  - Factors enhancing career satisfaction among female emergency physicians.
AB  - STUDY OBJECTIVE: Attrition rates in emergency medicine have been reported as high
      as 25% in 10 years. The number of women entering emergency medicine has been
      increasing, as has the number of female medical school graduates. No studies have
      identified factors that increase female emergency physician career satisfaction.
      We assess career satisfaction in women emergency physicians in the American
      College of Emergency Physicians (ACEP) and identify factors associated with
      career satisfaction. METHODS: The survey questionnaire was developed by querying
      3 groups: (1) ACEP women in the American Association of Women Emergency
      Physicians, the (2) Society for Academic Emergency Medicine Mentoring Women
      Interest Group, and (3) nonaffiliated female emergency physicians. Their
      responses were categorized into 6 main areas: schedule, relationships with
      colleagues, administrative support and mentoring, patient/work-related issues,
      career advancement opportunities, and financial. The study cohort for the survey
      included all female members of ACEP with a known e-mail address. All contact with
      survey recipients was exclusively through the e-mail that contained a uniform
      resource locator link to the survey itself. RESULTS: Two thousand five hundred
      two ACEP female members were sent the uniform resource locator link. The Web
      survey was accessed a total of 1,851 times, with a total of 1,380 surveys
      completed, an overall response rate of 56%. Most women were satisfied with their
      career as an emergency physician, 492 (35.5%) very satisfied, 610 (44.0%)
      satisfied, 154 (11.1%) neutral, 99 (7.1%) not satisfied, and 31 (2.3%) very
      unsatisfied. Significant factors for career satisfaction included amount of
      recognition at work, career advancement, schedule flexibility, and the fairness
      of financial compensation. Workplace factors associated with high satisfaction
      included academic practice setting and sex-equal opportunity for advancement and
      sex-equal financial compensation. CONCLUSION: Most of the ACEP female physicians
      surveyed were satisfied with their career choice of emergency medicine.
      Opportunities for career advancement, fairness in financial compensation, and
      schedule flexibility were key factors in career satisfaction among female
      emergency physicians.

PMID- 18342992
TI  - Electrocardiographic criteria for detecting acute myocardial infarction in
      patients with left bundle branch block: a meta-analysis.
AB  - STUDY OBJECTIVE: Numerous investigators have evaluated the ECG algorithm
      described by Sgarbossa et al to predict acute myocardial infarction in the
      presence of left bundle branch block and have arrived at divergent conclusions.
      To clarify the utility of the Sgarbossa ECG algorithm, we perform a systematic
      review and meta-analysis of these trials. METHODS: A structured search was
      applied to MEDLINE and Scopus databases, beginning with the year that the
      algorithm was derived (1996). Two reviewers independently screened citations,
      assessed for method quality, and extracted data (individual study
      characteristics, screening performance, and interobserver agreement) with a
      standardized extraction tool. We assessed qualifying studies for heterogeneity
      and generated summary estimates for the sensitivity, specificity, and positive
      and negative likelihood ratios with fixed-effect models. RESULTS: We identified
      11 studies with 2,100 patients that met criteria for at least 1 component of the
      analysis. Ten studies with 1,614 patients reported a Sgarbossa ECG algorithm
      score of greater than or equal to 3. These yielded a summary sensitivity of 20%
      (95% confidence interval [CI] 18% to 23%), specificity of 98% (95% CI 97% to
      99%), a positive likelihood ratio of 7.9 (95% CI 4.5 to 13.8), and a negative
      likelihood ratio of 0.8 (95% CI 0.8 to 0.9). The summary diagnostic odds ratio
      revealed homogeneity. Seven studies with 1,213 patients reported a Sgarbossa ECG
      algorithm score of greater than or equal to 2. These yielded sensitivities
      ranging from 20% to 79% and specificities ranging from 61% to 100%. Positive
      likelihood ratios ranged from 0.7 to 6.6 and negative likelihood ratios ranged
      from 0.2 to 1.1. The summary diagnostic odds ratio revealed heterogeneity. Intra-
      and interobserver agreement was substantial. Sensitivity analysis using the
      highest-quality studies yielded similar results. CONCLUSION: A Sgarbossa ECG
      algorithm score of greater than or equal to 3, representing greater than or equal
      to 1 mm of concordant ST elevation or greater than or equal to 1 mm ST depression
      in leads V1 to V3, is useful for diagnosing acute myocardial infarction in
      patients who present with left bundle branch block on ECG. The scoring system
      demonstrates good to excellent overall interobserver variability. A score of 2,
      representing 5 mm or more of discordant ST deviation, demonstrated ineffective
      positive likelihood ratios. A Sgarbossa ECG algorithm score of 0 is not useful in
      excluding acute myocardial infarction.

PMID- 18342993
TI  - Risk prediction with procalcitonin and clinical rules in community-acquired
      pneumonia.
AB  - STUDY OBJECTIVE: The Pneumonia Severity Index and CURB-65 predict outcomes in
      community-acquired pneumonia but have limitations. Procalcitonin, a biomarker of
      bacterial infection, may provide prognostic information in community-acquired
      pneumonia. Our objective is to describe the pattern of procalcitonin in community
      acquired pneumonia and determine whether procalcitonin provides prognostic
      information beyond the Pneumonia Severity Index and CURB-65. METHODS: We
      conducted a multicenter prospective cohort study in 28 community and teaching
      emergency departments. Patients presenting with a clinical and radiographic
      diagnosis of community-acquired pneumonia were enrolled. We stratified
      procalcitonin levels a priori into 4 tiers: I: less than 0.1; II: greater than
      0.1 to less than 0.25; III: greater than 0.25 to less than 0.5; and IV: greater
      than 0.5 ng/mL. Primary outcome was 30-day mortality. RESULTS: One thousand six
      hundred fifty-one patients formed the study cohort. Procalcitonin levels were
      broadly spread across tiers: 32.8% (I), 21.6% (II), 10.2% (III), and 35.4% (IV).
      Used alone, procalcitonin had modest test characteristics: specificity (35%),
      sensitivity (92%), positive likelihood ratio (1.41), and negative likelihood
      ratio (0.22). Adding procalcitonin to the Pneumonia Severity Index in all
      subjects minimally improved performance. Adding procalcitonin to low-risk
      Pneumonia Severity Index subjects (classes I to III) provided no additional
      information. However, subjects in procalcitonin tier I had low 30-day mortality,
      regardless of clinical risk, including those in higher risk classes (1.5% versus
      1.6% for those in Pneumonia Severity Index classes I to III versus classes IV/V).
      Among high-risk Pneumonia Severity Index subjects (classes IV/V), one quarter
      (126/546) were in procalcitonin tier I, and the negative likelihood ratio of
      procalcitonin tier I was 0.09. Procalcitonin tier I was also associated with
      lower burden of other adverse outcomes. Similar results were observed with CURB
      65 stratification. CONCLUSION: Selective use of procalcitonin as an adjunct to
      existing rules may offer additional prognostic information in high-risk patients.

PMID- 18342994
TI  - Can we improve how we treat patients with heart failure in the emergency
      department?

PMID- 18342995
TI  - Assessment of a novel screening score for nutritional risk in predicting
      complications in gastro-intestinal surgery.
AB  - BACKGROUND & AIMS: Malnutrition is a recognized risk factor for perioperative
      morbidity, but there is currently no standardized definition of malnutrition. The
      Nutrition Risk Screening 2002 score was recently proposed to identify patients at
      nutritional risk who may benefit from nutritional support therapy, and has been
      officially adopted by the European Society of Parenteral and Enteral Nutrition.
      The aim of this study was to assess the value of the Nutrition Risk Screening
      2002 score in predicting the incidence and severity of postoperative
      complications in gastrointestinal surgery. METHODS: We prospectively evaluated
      608 patients admitted for elective gastrointestinal surgery. Nutritional risk was
      defined by the Nutrition Risk Screening 2002 score and correlated to the
      incidence and severity of postoperative complications. Complications were
      classified using an established surgical complication classification. RESULTS:
      The overall incidence of nutritional risk was 14%. We observed a significantly
      higher complication rate of 40% (35 out of 87) in patients at nutritional risk,
      compared to 15% (81 out of 521) in patients with a normal score (p<0.001). The
      incidence of severe complications was significantly higher in patients at
      nutritional risk (54% versus 15%; p<0.001). The odds ratio to develop a
      complication was 2.8 in patients at risk (p=0.001), and 3.0 in patients with
      malignant disease (p<0.001). The median length of stay in nutritional risk
      patients was significantly longer (10 versus 4 days, p<0.001). CONCLUSION: The
      prevalence of nutritional risk patients in gastrointestinal surgery is high. We
      showed that nutritional risk screening using the NRS 2002 strongly predicts the
      incidence and severity of complications.

PMID- 18342996
TI  - Comparative assessment of a metabolically attenuated Mycoplasma gallisepticum
      mutant as a live vaccine for the prevention of avian respiratory mycoplasmosis.
AB  - In a previous study, signature sequence mutagenesis (SSM) was used to identify a
      mutant with a disruption of the gene encoding the metabolic factor,
      dihydrolipoamide dehydrogenase, and that mutant was designated Mg 7. The current
      study assessed the safety, immunogenicity and efficacy of Mg 7 in comparison to
      two commercially available vaccines (ts-11 and F) as well as a laboratory vaccine
      strain, GT5. Intratracheal vaccination of chickens with all four attenuated
      mutants induced varying levels of protection against intratracheal challenge with
      virulent Mycoplasma gallisepticum strain R(low). Mg 7 vaccinated chickens rapidly
      cleared the challenge strain, had lower histopathologic tracheal lesion scores
      when compared to unvaccinated chickens, and mounted a strong humoral anti-M.
      gallisepticum-specific IgG response. The IgG levels increased 2- to 3-fold upon
      R(low) challenge. Mg 7 induced a greater level of protection against
      intratracheal R(low) challenge than that observed with the other three attenuated
      strains, as evidenced by a lower recovery of R(low) from tracheas and lower
      histopathologic lesion scores in tracheas and air sacs. Based on these findings,
      Mg 7 appears to have good potential as a safe and effective vaccine for the
      prevention of avian mycoplasmosis.

PMID- 18342997
TI  - Longitudinal analyses of immune responses to Plasmodium falciparum derived
      peptides corresponding to novel blood stage antigens in coastal Kenya.
AB  - We have recently described 95 predicted alpha-helical coiled-coil peptides
      derived from putative Plasmodium falciparum erythrocytic stage proteins. Seventy
      peptides recognized with the highest level of prevalence by sera from three
      endemic areas were selected for further studies. In this study, we sequentially
      examined antibody responses to these synthetic peptides in two cohorts of
      children at risk of clinical malaria in Kilifi district in coastal Kenya, in
      order to characterize the level of peptide recognition by age, and the role of
      anti-peptide antibodies in protection from clinical malaria. Antibody levels from
      268 children in the first cohort (Chonyi) were assayed against 70 peptides.
      Thirty-nine peptides were selected for further study in a second cohort (Junju).
      The rationale for the second cohort was to confirm those peptides identified as
      protective in the first cohort. The Junju cohort comprised of children aged 1-6
      years old (inclusive). Children were actively followed up to identify episodes of
      febrile malaria in both cohorts. Of the 70 peptides examined, 32 showed
      significantly (p<0.05) increased antibody recognition in older children and 40
      showed significantly increased antibody recognition in parasitaemic children. Ten
      peptides were associated with a significantly reduced odds ratio (OR) for an
      episode of clinical malaria in the first cohort of children and two of these
      peptides (LR146 and AS202.11) were associated with a significantly reduced OR in
      both cohorts. LR146 is derived from hypothetical protein PFB0145c in PlasmoDB.
      Previous work has identified this protein as a target of antibodies effective in
      antibody dependent cellular inhibition (ADCI). The current study substantiates
      further the potential of protein PFB0145c and also identifies protein PF11_0424
      as another likely target of protective antibodies against P. falciparum malaria.

PMID- 18342998
TI  - A study of mechanisms responsible for incorporation of cesium and radiocesium
      into fruitbodies of king oyster mushroom (Pleurotus eryngii).
AB  - Ex vitro cultures of Pleurotus eryngii were carried out under controlled
      conditions using sterile medium composed of barley seeds. The influence of alkali
      and alkaline earth element salts (CsCl, KCl, NaCl, RbCl, and CaCl(2)) and
      tetraethylammonium chloride on incorporation of cesium, potassium, sodium,
      rubidium and calcium, and their distribution within fruitbodies, was examined.
      The results show that incorporation of cesium into fruitbodies was not suppressed
      by Na(+) and Rb(+) or tetraethylammonium chloride. However, it was inhibited by
      Ca(2+) and stimulated by high concentrations of K(+). The inhibition of cesium
      incorporation by Ca(2+), lack of influence of tetraethylammonium chloride and
      stimulation by high K(+) concentrations suggest that there may exist two pathways
      of passive transport of cesium in mycelium: (i) uptake mediated by a non-specific
      potassium channel localised in plasmalemma (similar to voltage-insensitive cation
      channel, VICC) followed by diffusive transport inside hyphae and (ii)
      extracellular transport from the medium through inter-hyphal cavities into
      fruitbodies. The results highlight distinctiveness of mechanisms responsible for
      the uptake and incorporation of cesium in mushrooms and plants.

PMID- 18342999
TI  - Piezoelectric surgery: twenty years of use.
AB  - The use of ultrasonic vibrations for the cutting of bone was first introduced two
      decades ago. Piezoelectric surgery is a minimally invasive technique that lessens
      the risk of damage to surrounding soft tissues and important structures such as
      nerves, vessels, and mucosa. It also reduces damage to osteocytes and permits
      good survival of bony cells during harvesting of bone. Piezoelectric surgery was
      first used by oral and maxillofacial surgeons for osteotomies, but recently some
      specific applications in neurosurgery and orthopaedics have been proposed. We
      review the different applications of piezoelectric surgery.

PMID- 18343000
TI  - Chinese midwives' views on a proposed midwife-led normal birth unit.
AB  - OBJECTIVE: to investigate and assess Chinese midwives' views of their roles and
      ability to practice in a proposed midwife-led normal birth unit (MNBU). DESIGN: a
      self-completed questionnaire supplemented with semi-structured telephone
      interviews. Memos, diaries, correspondence and comments of Chinese collaborators
      were also accessed. SETTING: six hospitals in Hangzhou, the capital of Zhejiang
      province. PARTICIPANTS: 143 midwives were contacted and completed the
      questionnaire survey. Three midwives were subsequently interviewed. FINDINGS: the
      response rate was 100%; 86% of midwives supported the development of an MNBU, and
      94.4% expressed confidence that they would be able to practice in an MNBU. The
      study shed new light on: (1) the meaning of an MNBU in the Chinese context; (2)
      the need for development of an MNBU; (3) role conflicts among midwives, doulas,
      nurses and obstetricians; (4) professional expertise and tension; and (5) the low
      status of Chinese midwives. CONCLUSION: the proposed MNBU is welcomed by Chinese
      midwives. Their consensus and confidence show that there is enthusiasm for this
      project to proceed. However, the Chinese have never thought of MNBU services
      before. There is a need to develop well-structured philosophy, policy, procedures
      and outcome measures. IMPLICATIONS FOR PRACTICE: the findings highlight the
      importance of an MNBU to re-establish Chinese midwives' support of physiological
      childbirth. The extent to which Chinese midwives understand an MNBU could be
      further explored. The result may provide a possible route to the continuity of
      midwifery care and support.

PMID- 18343001
TI  - Effect of foot rotation on knee kinetics and hamstring activation in older adults
      with and without signs of knee osteoarthritis.
AB  - BACKGROUND: To determine the effects of changing the natural foot progression
      angle during gait (internal and external foot rotation) on the knee's adduction
      moment, lateral-medial shear force, and the ratio of medial-lateral hamstring
      muscle activation in those with signs of knee osteoarthritis and a matched
      healthy control group. METHODS: Twelve subjects with signs of knee osteoarthritis
      and 12 matched healthy control subjects were evaluated. A 3D gait analysis system
      calculated forces and moments at the knee while the subjects walked in three
      conditions: (1) normal foot position, (2) external foot rotation, (3) internal
      foot rotation. Medial and lateral hamstring EMG data was also collected
      simultaneously and used to calculate the medial-lateral hamstring activation
      ratio during the stance phase of the gait cycle. Repeated measures ANOVAs were
      used to compare foot rotation conditions within each group; while between group
      comparisons were performed in the normal rotation condition only using t-tests.
      FINDINGS: Those with knee osteoarthritis (OA) had an increased late stance knee
      adduction moment and a decreased medial-lateral hamstring activation ratio as
      compared to the healthy control group. Also, external foot rotation decreased the
      late stance knee adduction moment, lateral-medial shear force, and hamstring
      activation ratio. However, internal foot rotation did not increase these
      measures. INTERPRETATION: Changes in foot position during gait have the ability
      to alter both the external loading of the knee joint and hamstring muscle
      activation patterns during gait. This may have implication in helping to unload
      the knee's articular cartilage.

PMID- 18343002
TI  - Management of viral hepatitis in hematologic malignancies.
AB  - Viral hepatitis is the third major cause of liver dysfunction in allogeneic
      transplant recipients and has become a significant concern in patients with
      hematological malignancies receiving chemotherapy. Thus, identification of
      patients at risk for viral hepatitis is very important when evaluating and
      treating hematological malignancies. Serologic screening for all patients should
      include anti-HCV, hepatitis B surface antigen (HBsAg), hepatitis B surface
      antibody (anti-HBs), and hepatitis B core antibody (anti-HBc) testing. Current
      therapies for hepatitis B (HBV) virus infection are aimed at viral suppression,
      while treatment for hepatitis C (HCV) virus can eradicate infection in many
      treated patients. To prevent HBV viral reactivation, prophylaxis with nucleoside
      analogues should be initiated for all HBsAg-positive patients. HCV infection
      appears to have little impact on short-term survival after bone marrow
      transplantation (BMT), but eventually can impact long-term survival due to
      progression of liver disease. In this review we will highlight the mechanisms of
      virus reactivation, clinical manifestations, and management strategies to
      minimize acute and chronic morbidity in this population.

PMID- 18343003
TI  - High-level Zn and Cd tolerance in Silene paradoxa L. from a moderately Cd- and Zn
      contaminated copper mine tailing.
AB  - Cadmium and zinc tolerance were examined in populations of Silene paradoxa, one
      from uncontaminated calcareous soil (CVD) and one from a mine tailing (FC) (Cd<1
      15 ppm, Zn 400-1300 ppm, pH 2-6). The mine population exhibited extremely high Zn
      and Cd tolerance levels, although the degrees of Cd and Zn enrichment relatively
      low at the population site. Cd and Zn hypertolerance in FC were associated with
      reduced rates of accumulation of these metals, both in roots and shoots (Cd), or
      exclusively in shoots (Zn). However, exclusion potentially explained only a minor
      part of the superior tolerance in FC. Cd hypertolerance in FC was associated with
      decreased, rather than enhanced phytochelatin accumulation. The remarkably high
      levels of Cd and Zn hypertolerance in FC might relate to the low soil pH, due to
      oxidation of sulphide minerals, and the absence of soil organic matter at the FC
      site.

PMID- 18343004
TI  - The influence of nitrogen in stemflow and precipitation on epiphytic bryophytes,
      Isothecium myosuroides Brid., Dicranum scoparium Hewd. and Thuidium tamariscinum
      (Hewd.) Schimp of Atlantic oakwoods.
AB  - The spatial relationship between the concentration and deposition of the major
      ions in precipitation and stemflow and their influence on the tissue nitrogen
      concentration of three epiphytic bryophytes on Quercus petraea (Matt) Liebl. and
      Q. robur L. was investigated at seven UK Atlantic oak woodland sites with a range
      of total N deposition of 55-250 mmol m(-2). The main driver of change in tissue N
      concentrations of three epiphytic bryophytes (Isothecium myosuroides Brid.
      (Eurhynchium myosuroides (Brid.) Schp.), Dicranum scoparium Hewd. and Thuidium
      tamariscinum (Hewd.) Schimp.) was total N deposition in stemflow, dominated by
      ammonium deposition. The three epiphytic species also showed strong relationships
      between tissue N concentration and total N deposition in rainfall but a poor
      correlation with total N ion concentration in rainfall. This study shows that
      epiphytic bryophytes utilise stemflow N and thus increase their risk from inputs
      of total N deposition compared to terricolous species at the same site.

PMID- 18343005
TI  - Information and communications technology for future health systems in developing
      countries.
AB  - There has been much discussion of the role that recent advances in information
      and communication technologies (ICTs) could play in improving health systems in
      developing countries, but limited independent analysis of existing applications.
      Combining a case study approach with a general discussion of the issues, this
      paper attempts to assess the potential benefits of a diverse range of ICT
      innovations and some of the constraints they will need to overcome. Four broad
      areas are considered: improvements in traditional health information systems;
      computer-aided diagnosis and treatment monitoring; a range of applications
      generically labelled 'telemedicine'; and the use of ICT to inform general
      populations on health and healthcare. The final section speculates on the
      possible medium-term impacts of ICT in terms of improving the performance of
      existing systems, allowing scope for radical innovations, or even changing basic
      assumptions about the provider-patient relationship.

PMID- 18343006
TI  - Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic
      receptor regulation: interactions with clozapine actions and attentional
      performance in rats.
AB  - Blockade of NMDA glutamate receptors with dizocilpine (MK-801) has been shown to
      cause substantial cognitive deficits and has been used to model symptoms of
      schizophrenia. Nicotine or nicotinic agonists, in contrast, may enhance cognitive
      or attentional functions and be of therapeutic potential in schizophrenia.
      Nicotinic-glutamatergic interactions, therefore, may have important implications
      in cognitive functions and antipsychotic treatments. Clozapine, a widely used
      antipsychotic drug, has been shown in some studies to be effective in
      ameliorating the cognitive deficits associated with schizophrenia. However, there
      is some evidence to suggest that clozapine similar to haloperidol may impair
      sustained attention in rats. In this study, we sought to determine whether
      chronic nicotine or dizocilpine may modify the effects of acute clozapine on
      attentional parameters and whether the behavioral effects would correlate with
      nicotinic or NMDA receptor densities in discrete brain regions. Adult female rats
      trained on an operant visual signal detection task were given 4 weeks of nicotine
      (5 mg/kg/day), dizocilpine (0.15 mg/kg/day), the same doses of both nicotine and
      dizocilpine as a mixture, or saline by osmotic minipump. While on chronic
      treatment, rats received acute injections of various doses of clozapine (0,
      0.625, 1.25, 2.5 mg/kg, sc) 10 min prior to tests on attentional tasks. The pumps
      were removed on day 28 and 24 h later the animals were sacrificed for
      measurements of receptor densities in specific brain regions. The percent correct
      hit as a measure of sustained attention was significantly impaired by clozapine
      in a dose-related manner. Neither chronic nicotine nor dizocilpine affected this
      measure on their own or modified the effects of clozapine. Both nicotine and
      dizocilpine affected the receptor bindings in a region specific manner and their
      combination further modified the effects of each other in selective regions.
      Attentional performance was inversely correlated with alpha-bungarotoxin binding
      in the frontal cortex only. In conclusion, the data suggest attentional
      impairments with clozapine alone and no modification of this effect with nicotine
      or dizocilpine. Moreover, cortical low affinity nicotinic receptors may have a
      role in attentional functions.

PMID- 18343007
TI  - Calcineurin A gamma and B gene expressions in the whole blood in Japanese
      patients with schizophrenia.
AB  - Calcineurin (CaN) has been regarded as a candidate gene for vulnerability of
      schizophrenia. Although CaN gene expression has been investigated with postmortem
      brain specimens or in association studies, little information is available about
      CaN gene expression levels in peripheral sources. We obtained whole blood samples
      from 16 patients with schizophrenia and 16 controls, and total RNA was extracted.
      CaN A gamma and CaN B genes were analyzed by quantitative RT-PCR. In the patient
      group, expression levels of both genes were correlated with psychopathology, as
      measured by the Brief Psychiatric Rating Scale (BPRS), and neuroleptic dose. No
      significant differences in CaN A gamma or CaN B gene expression were observed
      between patients with schizophrenia and normal controls. Linear regression
      analysis revealed that the CaN A gamma gene expression level was associated with
      the BPRS score but not with neuroleptic dose. Neither of the clinical variables
      was associated with the CaN B gene expression level. The results of this study
      suggest that the CaN A gamma gene may be an effective predictor of the
      progression of psychosis. The effect of medications on expression of CaN genes
      requires further study.

PMID- 18343008
TI  - Validation of the electronic Visual Analogue Scale of Anxiety.
AB  - Currently, the use of electronic scales is increasing rapidly, which is not
      surprising considering its accuracy, the ease of use and the increased
      compliance. The value of Visual Analogue Scales as a mean to objectify subjective
      variables has long been recognised. The current study aimed to validate the
      electronic Visual Analogue Scale of Anxiety (eVAAS). Seventy-one subjects,
      control subjects (n=46) and Panic Disorder patients (n=25), filled out the paper
      VAAS and the eVAAS in a randomised order. Panic was provoked using 35% CO(2)
      inhalation allowing us to include maximal scores in our analyses. The correlation
      between eVAAS and pVAAS was very strong and highly significant (r=0.98, p<0.001).
      pVAAS scores were slightly higher than eVAAS scores (p<0.001), but this
      difference is clinically unimportant. The VAAS established on a tablet PC is a
      useful and valid measure of anxiety and holds intrinsic benefits for anxiety
      assessment.

PMID- 18343009
TI  - Percutaneous absorption of aromatic amines - a contribution for human health risk
      assessment.
AB  - Several aromatic amines (AA) are human carcinogens. AA are widely-used, e.g., in
      the rubber industry. The uptake of AA at the workplace occurs by inhalation and
      percutaneous absorption. At present there are no risk assessment studies for
      percutaneous AA absorption using occupationally relevant concentrations. We
      conducted diffusion cell experiments for aniline (ANI), o-toluidine (OT), 4,4'
      methylenedianiline (MDA) and N-phenyl-2-naphthylamine (PBNA). Excised human skin
      was exposed to different AA concentrations in vehicles containing water and
      solvents. Recovery for ANI in receptor fluid was about 20-38% and for MDA 15%
      over 24h. PBNA could not be detected in the receptor fluid. Further data for OT
      and beta-naphthylamine (BNA) were considered from our recent study. A semi
      quantitative percutaneous absorption ranking for AA was derived:
      BNA>OT>ANI>MDA>PBNA. For aqueous ANI solutions up to saturation a linear
      relationship of exposed dose and penetrated amount was observed. However, a
      linear extrapolation of the flux of neat compounds, as often recommended for risk
      assessment policies, underestimates considerably the percutaneous uptake. The in
      vitro data support our recent findings in rubber industry workers that the
      percutaneous absorption may significantly contribute to overall exposure of AA.

PMID- 18343010
TI  - Lactobacillus rhamnosus strain GG restores alkaline phosphatase activity in
      differentiating Caco-2 cells dosed with the potent mycotoxin deoxynivalenol.
AB  - Deoxynivalenol (DON) contamination of cereal crops occurs frequently, and may
      cause acute exposure at high levels or chronic more moderate exposure. DON has
      proven toxicity including restriction of enterocyte differentiation, which may
      play a part in DON induced gastroenteritis. The probiotic bacteria Lactobacillus
      rhamnosus strain GG (GG) can bind DON, and therefore potentially restrict
      bioavailability of this toxin. Binding efficacy is not significantly altered by
      heat treatment, and therefore this in vitro study evaluated whether heat
      inactivated GG could restore the differentiation process in Caco-2 cells, using
      alkaline phosphatase (ALP) activity as a marker of differentiation. DON
      (200ng/mL) caused a significant (p<0.001) 36% reduction in ALP activity (1598+/
      137U/mg protein) compared to untreated cells (2502+/-80U/mg). A dose dependant
      restoration of ALP activity was observed where DON treated cells were co
      incubated with heat inactivated GG (1719+/-84; 2007+/-142; 2272+/-160U/mg for GG
      at 1x10(4) (p>0.9), 1x10(7) (p<0.001), and 1x10(10)CFU/mL (p<0.001),
      respectively). Co-incubation of the non-binding strain, LC-705 (1x10(10)CFU/mL),
      with DON did not significantly restore the ALP (1841+/-97U/mg, p<0.077) compared
      to DON only treated cells. When viable GG were co-incubated with DON a similar
      restoration of ALP activity was observed as seen for heat inactivated GG. These
      combined data suggest that the major effect of GG on restoring ALP activity, and
      therefore Caco-2 cell differentiation, was due to specific binding of DON, with
      possibly a more minor role of non-specific bacterial interference.

PMID- 18343011
TI  - Effects of short-term supplementation of clinoptilolite in colostrum and milk on
      hematology, serum proteins, performance, and health in neonatal dairy calves.
AB  - In recent years, the use of both natural and synthetic zeolites in animal
      nutrition has increased, mainly to improve their performance, health, and to
      protect against mycotoxins intoxication. Thirty calves were used in the present
      study for the determination of the effects of clinoptilolite supplementation on
      hematology, serum proteins, performance, and health. The animals were divided
      equally into three groups (control, test 1 and test 2). The three groups of
      calves were homogeneous for parity of dams, sex, and month of birth. For test 1
      group, clinoptilolite in the concentration of 2% of each colostrum meal was added
      for 48h and for test 2 group, clinoptilolite in the concentration of 2% was added
      to each colostrum and milk meal for 14 days. Blood samples were taken from all
      calves 12h after birth and at the end of the first, second, third, forth, fifth
      and sixth weeks of life (end of the experiment: 42 days of life) and analyzed for
      hematology, plasma fibrinogen and for total protein, albumin, beta and gamma
      globulin measurement. Performance and health of calves were also recorded during
      the experiment. For statistical analysis of data a repeated measures approach
      using ANOVA with Mixed linear models, and chi-test was used. Clinoptilolite
      supplementation had significant effect on the values of hematocrit (HCT), red
      cell count (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), monocyte
      (Mono), and albumin (Alb). The values of most above parameters were significantly
      higher in test group 2, except MCV that was significantly lower in test group 1
      than other trial groups (p<0.05). No significant difference was seen for other
      measured parameters, performance, and health between trial groups.

PMID- 18343012
TI  - Effect of uranyl nitrate on enzymes of carbohydrate metabolism and brush border
      membrane in different kidney tissues.
AB  - Uranium, the heaviest of the naturally occurring elements is widely present as
      environmental contaminant from natural deposits, industrial emissions and most
      importantly from modern weapons. Histopathological examinations revealed that
      uranyl nitrate (UN) exposure caused severe damage to pars recta of renal proximal
      tubule. However, biochemical events involved in cellular response to renal injury
      are not completely elucidated. We hypothesized that UN exposure would severely
      damage kidney tissues and alter their metabolic functions. Rats were treated with
      a single nephrotoxic dose of UN (0.5mg/kg body weight) i.p. After 5d, effect of
      UN was studied on the activities of various enzymes of carbohydrate metabolism,
      brush border membrane (BBM) and oxidative stress in different kidney tissues.
      Activity of lactate dehydrogenase increased whereas activities of isocitrate,
      succinate and malate dehydrogenases, glucose-6-phosphatase and fructose-1,6
      bisphosphatase significantly decreased by UN exposure. Activity of glucose-6
      phosphate dehydrogenase decreased whereas that of NADP-malic enzyme increased.
      The activities of BBM enzymes were significantly lowered and after dissociation
      from BBM excreted in urine. Lipid peroxidation and the activities of superoxide
      dismutase and glutathione peroxidase increased whereas catalase activity
      decreased by UN. UN treatment caused specific alterations in the activities of
      metabolic and membrane enzymes and perturbed antioxidant defenses.

PMID- 18343013
TI  - Mucoadhesion, hydration and rheological properties of non-aqueous delivery
      systems (NADS) for the oral cavity.
AB  - OBJECTIVES: Effective delivery of oral care actives from conventional hydrogel
      formulations is often compromised by poor retention associated with shear forces
      present in the mouth, salivary washout and over-hydration of the gel which can
      lead to structural breakdown and adhesive failure. Non-aqueous gels offer the
      opportunity to formulate rheologically acceptable vehicles with higher
      concentrations of bioadhesive polymer than is possible using water as the primary
      solvent. Accordingly, this study describes the formulation and characterisation
      of the rheology, hydration and bioadhesive properties of a range of non-aqueous
      delivery systems (NADS). METHODS: The formulations were composed principally of
      glycerol, with varying amounts of polyethylene glycol (PEG) 400 and Carbopol 974P
      being incorporated in the ranges 0-31.34% and 0-4% (w/w). Work of adhesion (WOA)
      and maximum force of detachment (Fmax) were determined using a Dartec tensile
      tester after application of a normal force. Rheology was assessed using a Bohlin
      CS CVO rheometer. RESULTS: WOA and Fmax increased with increasing compression
      time and Carbopol concentration. Addition of 30% (w/w) PEG 400 to the formulation
      containing 2% Carbopol in glycerol improved bioadhesive function. Formulation
      rheology was largely controlled by the Carbopol concentration, and to a lesser
      extent by the concentration of PEG 400 and these, in turn, largely determined the
      bioadhesion parameters and rates of hydration. CONCLUSION: The results of this in
      vitro study suggest that bioadhesion, and consequently potential drug
      bioavailability, would be enhanced by use of a water miscible non-aqueous
      delivery vehicle such as glycerol containing a bioadhesive polymer such as
      Carbopol with the addition of controlled amounts of PEG as plasticiser.

PMID- 18343014
TI  - Removal of chromium (VI) from aqueous solution using walnut hull.
AB  - In this study, removal of chromium (VI) from aqueous solution by walnut hull (a
      local low-cost adsorbent) was studied. The extent of adsorption was investigated
      as a function of solution pH, contact time, adsorbent and adsorbate
      concentration, reaction temperature and supporting electrolyte (sodium chloride).
      The Cr (VI) removal was pH-dependent, reaching a maximum (97.3%) at pH 1.0. The
      kinetic experimental data were fitted to the first-order, modified Freundlich,
      intraparticle diffusion and Elovich models and the corresponding parameters were
      obtained. A 102.78 kJ/mol Ea (activation energy) for the reaction of chromium
      (VI) adsorption onto walnut indicated that the rate-limiting step in this case
      might be a chemically controlled process. Both the Langmuir and Freundlich
      isotherms were suitable for describing the biosorption of chromium (VI) onto
      walnut hull. The uptake of chromium (VI) per weight of adsorbent increased with
      increasing initial chromium (VI) concentration up to 240-480 mg/L, and decreased
      sharply with increasing adsorbent concentration ranging from 1.0 to 5.0 g/L. An
      increase in sodium chloride (as supporting electrolyte) concentration was found
      to induce a negative effect while an increase in temperature was found to give
      rise to a positive effect on the chromium (VI) adsorption process. Compared to
      the various other adsorbents reported in the literature, the walnut hull in this
      study shows very good promise for practical applicability.

PMID- 18343015
TI  - Use of an ultrasound blood-mimicking fluid for Doppler investigations of
      turbulence in vitro.
AB  - Turbulence is an important factor in the assessment of stenotic disease and a
      possible causative mechanism for thromboembolism. Previous Doppler studies of
      turbulence have typically used whole-blood preparations or suspensions of
      erythrocytes. Recently, a water-glycerol based blood-mimicking fluid (BMF) has
      been developed for use in Doppler ultrasound studies. This fluid has desirable
      ultrasound properties but it has not previously been described during in vitro
      investigations of turbulence intensity. We report on investigations of grid
      generated and constrained-jet turbulence in an in vitro test system. The BMF was
      found to generate significant levels of turbulence during steady flow at
      physiological flow rates, producing turbulent patterns in the distal region that
      were consistent with previous studies. Turbulence intensity increased
      significantly with flow rate (p < 0.005) for both the constrained jet and the
      constrained grid. Based on our observations, we conclude that a water-glycerol
      based BMF provides a suitable working fluid during in vitro investigations of
      turbulence using Doppler ultrasound.

PMID- 18343016
TI  - On the differences between two-dimensional and three-dimensional simulations for
      assessing elastographic image quality: a simulation study.
AB  - In this work, we introduced an elastographic simulation framework, which
      estimates upper bounds on elastographic image quality by accounting for three
      dimensional (3D) tissue motion and the 3D nature of the ultrasound beam. For the
      boundary conditions and the range of applied strains considered in this study, it
      was observed that for applied strains smaller than 0.7%, fast two-dimensional
      (2D) simulations and 3D simulations predicted similar upper bounds on
      elastographic signal-to-noise (SNR(e)) and contrast-to-noise ratios (CNR(e));
      however, for applied strains greater than 0.7%, the predictions by 2D simulations
      grossly overestimated the achievable results when compared with upper bound
      results from 3D simulations. It was also found that linear increments in the
      elevational-to-lateral beamwidth ratio (beam ratio) resulted in nonlinear
      degradation in the achievable upper bounds on elastographic signal-to-noise
      ratio. For the modulus contrast ratio of ten between the target and the
      background, the peak difference in the prediction of contrast-to-noise by 2D and
      3D simulations was approximately 10 dB, whereas, for modulus contrast ratio of
      1.5, the peak difference increased to approximately 30 dB. No significant
      difference was observed between the spatial resolution predicted by 2D and 3D
      simulations; however, increase in beam ratio resulted in decrease in target
      detectability, especially at lower modulus contrast ratios.

PMID- 18343018
TI  - Doppler ultrasound compatible plastic material for use in rigid flow models.
AB  - A technique for the rapid but accurate fabrication of multiple flow phantoms with
      variations in vascular geometry would be desirable in the investigation of
      carotid atherosclerosis. This study demonstrates the feasibility and efficacy of
      implementing numerically controlled direct-machining of vascular geometries into
      Doppler ultrasound (DUS)-compatible plastic for the easy fabrication of DUS flow
      phantoms. Candidate plastics were tested for longitudinal speed of sound (SoS)
      and acoustic attenuation at the diagnostic frequency of 5 MHz. Teflon was found
      to have the most appropriate SoS (1376 +/- 40 m s(-1) compared with 1540 m s(-1)
      in soft tissue) and thus was selected to construct a carotid bifurcation flow
      model with moderate eccentric stenosis. The vessel geometry was machined directly
      into Teflon using a numerically controlled milling technique. Geometric accuracy
      of the phantom lumen was verified using nondestructive micro-computed tomography.
      Although Teflon displayed a higher attenuation coefficient than other tested
      materials, Doppler data acquired in the Teflon flow model indicated that
      sufficient signal power was delivered throughout the depth of the vessel and
      provided comparable velocity profiles to that obtained in the tissue-mimicking
      phantom. Our results indicate that Teflon provides the best combination of
      machinability and DUS compatibility, making it an appropriate choice for the
      fabrication of rigid DUS flow models using a direct-machining method.

PMID- 18343017
TI  - Ultrasound simulation in the distal radius using clinical high-resolution
      peripheral-CT images.
AB  - The overall objective of this research is to develop an ultrasonic method for
      noninvasive assessment of the distal radius. The specific objective of this study
      was to examine the propagation of ultrasound through the distal radius and
      determine the relationships between bone mass and architecture and ultrasound
      parameters. Twenty-six high-resolution peripheral-CT clinical images were
      obtained from a set of subjects that were part of a larger study on secondary
      osteoporosis. A single midsection binary slice from each image was selected and
      used in the two-dimensional (2D) simulation of an ultrasound wave propagating
      from the anterior to the posterior surfaces of each radius. Mass and
      architectural parameters associated with each radius, including total (trabecular
      and cortical) bone mass, trabecular volume fraction, trabecular number and
      trabecular thickness were computed. Ultrasound parameters, including net time
      delay (NTD), broadband ultrasound attenuation (BUA) and ultrasound velocity (UV)
      were also evaluated. Significant correlations were found between NTD and total
      bone mass (R2 = 0.92, p < 0.001), BUA and trabecular number (R2 = 0.78, p < 0.01)
      and UV and trabecular bone volume fraction (R2 = 0.82, p < 0.01). There was only
      weak, statistically insignificant correlation (R2 < 0.14, p = 0.21) found between
      trabecular thickness and any of the ultrasound parameters. The study shows that
      ultrasound measurements are correlated with bone mass and architecture at the
      distal radius and, thus, ultrasound may prove useful as a method for noninvasive
      assessment of osteoporosis and fracture risk.

PMID- 18343019
TI  - Effects of acoustic insonation parameters on ultrasound contrast agent
      destruction.
AB  - Ultrasound contrast agents (UCAs) are used to enhance the acoustic backscattered
      intensity of blood and thereby assist the assessment of blood perfusion.
      Characterization of UCA destruction provides important information for the design
      of contrast-assisted perfusion imaging. High-speed optical observation of single
      microbubble destruction during acoustic insonation has been performed in previous
      studies. The results identified that pressure, center frequency and transmission
      phase have significant effects on the fragmentation threshold. We proposed an
      acoustic-based experiment method to demonstrate the relationship between
      different acoustic exposure conditions and the degree of UCA destruction. The
      method also provides a simple and convenient way to determine the microbubble
      destruction threshold. The experiments introduced three insonation parameters,
      including acoustic pressure (0 to 1 MPa), pulse frequency (1, 2.25, 5 and 7.5
      MHz) and pulse length (1 to 10 cycles). The term of surviving percentage (SP) was
      proposed to represent the ratio of UCA backscattered power with and without
      acoustic insonation. The results showed that the SP decreased with decreasing
      pulse frequency, but with increasing transmission acoustic pressure and pulse
      length. In addition, there was an exponential relationship between SP and
      acoustic pressure, and thus the UCA destruction pressure threshold could be
      predicted from the fitted exponential curve. The results also show that the
      degree of UCA destruction was not related to mechanical index (MI). Potential
      applications of this method include UCA high-resolution destruction/replenishment
      imaging model, microbubble cavitation, sonoporation in drug delivery and gene
      therapy.

PMID- 18343020
TI  - Reliability of measuring sciatic and tibial nerve movement with diagnostic
      ultrasound during a neural mobilisation technique.
AB  - Diagnostic ultrasound provides a technique whereby real-time, in vivo analysis of
      peripheral nerve movement is possible. This study measured sciatic nerve movement
      during a "slider" neural mobilisation technique (ankle dorsiflexion/plantar
      flexion and cervical extension/flexion). Transverse and longitudinal movement was
      assessed from still ultrasound images and video sequences by using frame-by-frame
      cross-correlation software. Sciatic nerve movement was recorded in the transverse
      and longitudinal planes. For transverse movement, at the posterior midthigh (PMT)
      the mean value of lateral sciatic nerve movement was 3.54 mm (standard error of
      measurement [SEM] +/- 1.18 mm) compared with anterior-posterior/vertical (AP)
      movement of 1.61 mm (SEM +/- 0.78 mm). At the popliteal crease (PC) scanning
      location, lateral movement was 6.62 mm (SEM +/- 1.10 mm) compared with AP
      movement of 3.26 mm (SEM +/- 0.99 mm). Mean longitudinal sciatic nerve movement
      at the PMT was 3.47 mm (SEM +/- 0.79 mm; n = 27) compared with the PC of 5.22 mm
      (SEM +/- 0.05 mm; n = 3). The reliability of ultrasound measurement of transverse
      sciatic nerve movement was fair to excellent (Intraclass correlation coefficient
      [ICC] = 0.39-0.76) compared with excellent (ICC = 0.75) for analysis of
      longitudinal movement. Diagnostic ultrasound presents a reliable, noninvasive,
      real-time, in vivo method for analysis of sciatic nerve movement.

PMID- 18343021
TI  - The acoustic properties, centered on 20 MHZ, of an IEC agar-based tissue
      mimicking material and its temperature, frequency and age dependence.
AB  - The purpose of this study was to characterize the ultrasonic properties of agar
      based tissue-mimicking materials (TMMs) at ultrasound frequencies centered around
      20 MHz. The TMM acoustic properties measured are the amplitude attenuation
      coefficient alpha (dB cm(-1)MHz(-1)), the speed of sound (ms(-1)) and the
      backscattered power spectral density (distribution of power per unit frequency
      normalized to the total received power) characteristics of spectral slope (dB
      MHz(-1)), y-axis intercept (dB) and reflected power (dB). The acoustic properties
      are measured over a temperature range of 22 to 37 degrees C. An intercomparison
      of results between two independent ultrasound measurement laboratories is also
      presented. A longitudinal study of the acoustic properties over a period of two
      years is also detailed, and the effect of water immersion on the acoustic
      properties of TMM is measured. In addition, the physical parameters of mass
      density rho (kg m(-3)) and specific heat capacity C (J kg(-1) K(-1)) are
      included. The measurement techniques used were based on the substitution
      technique using both broadband and narrowband pulses centered on 20 MHz. Both the
      attenuation coefficient and speed of sound (both group and phase) showed good
      agreement with the expected values of 0.5 dB cm(-1) MHz(-1) and 1540 ms(-1),
      respectively, with average values over the three-year period of 0.49 dBcm(-1)MHz1
      (SD +/- 0.05) and 1540.9 ms(-1) (SD +/- 8.7). These results also showed agreement
      between the two independent measurement laboratories. Speed of sound and
      attenuation coefficient were shown to change with temperature with rates of + 2.1
      m s(-1) degrees C(-1) and -0.005 dB cm(-1) MHz(-1) degrees C(-1), respectively.
      Attenuation changed linearly with frequency at the high frequency range of 17 to
      23 MHz, and speed of sound was found to be independent of frequency in this
      range. The spectral slope of relative backscattered power for the material
      increased with frequency at typically 1.5 dB MHz(-1). This compared favorably
      with theoretical spectral slope values, calculated for a variety of scatterer
      sizes, albeit at a lower frequency range. It is also noticed that, on
      extrapolation back to lower frequencies, the backscatter is comparable with that
      measured at 7 MHz. Overall, this non-commercial agar-based TMM is shown to
      perform as expected at the higher frequency range of 17 to 23 MHz and is seen to
      retain its acoustic properties of attenuation and speed of sound over a three
      year period.

PMID- 18343022
TI  - The influence of fragmentation on the acoustic response from shrinking bubbles.
AB  - Bubble disruption is associated with the response of ultrasound contrast agents
      (UCAs) exposed to high acoustic pressures. This behavior is important for bubble
      detection techniques as well as flow quantitation and some proposed therapeutic
      applications. Previous work has measured acoustically the disruption threshold
      and postdisruption echo from populations of microbubbles. This suggests a model
      for UCA disruption whereby ultrasound breaks their shell, leaving free gas
      bubbles. Diffusion of gas causes the bubbles to shrink and, consequently, reduces
      the measured backscatter echo over time. In this work, similar bubbles containing
      three different gases were measured and their echo behavior with time compared
      with a simple simulation based on diffusion of gas out of the bubble. It was
      found that, in general, the simulations and experiments compared well at low
      disruption pressures. Incorporating bubble fragmentation in the simulation model
      brought its results closer to experiment.

PMID- 18343023
TI  - Endocannabinoids affect the reproductive functions in teleosts and amphibians.
AB  - Following the discovery in the brain of the bonyfish Fugu rubripes of two genes
      encoding for type 1 cannabinoid receptors (CB1A and CB1B), investigations on the
      phylogeny of these receptors have indicated that the cannabinergic system is
      highly conserved. Among the multiple functions modulated by
      cannabinoids/endocannabinoids through the CB1 receptors one of the more
      investigated is the mammalian reproduction. Therefore, since studies performed in
      animal models other than mammals might provide further insight into the biology
      of these signalling molecules, the major aim of the present paper was to review
      the comparative data pointing toward the endocannabinoid involvement in the
      reproductive control of non-mammalian vertebrates, namely bonyfish and
      amphibians. The expression and distribution of CB1 receptors were investigated in
      the CNS and gonads of two teleosts, Pelvicachromis pulcher and Carassius auratus
      as well as in the anuran amphibians Xenopus laevis and Rana esculenta. In general
      the large diffusion of neurons targeted by cannabinoids in both fish and
      amphibian forebrain indicate endocannabinoids as pivotal local messengers in
      several neural circuits involved in either sensory integrative activities, like
      the olfactory processes (in amphibians) and food response (in bonyfish), or
      neuroendocrine machinery (in both). By using immunohistochemistry for CB1 and
      GnRH-I, the codistribution of the two signalling molecules was found in the fish
      basal telencephalon and preoptic area, which are key centers for gonadotropic
      regulation in all vertebrates. A similar topographical codistribution was
      observed also in the septum of the telencephalon in Rana esculenta and Xenopus
      laevis. Interestingly, the double standard immunofluorescence on the same brain
      section, aided with a laser confocal microscope, showed that in anurans a subset
      of GnRH-I neurons exhibited also the CB1 immunostaining. The fact that CB1-LI-IR
      was found indeed in the FSH gonadotrophs of the Xenopus pituitary gland and CB1
      receptors together with the fatty acid amide hydrolase, the degradative enzyme of
      the endocannabinoid anandamide, were demonstrated in both bonyfish and frog
      gonads, strongly suggests that endocannabinoids are involved in central and
      peripheral gonadotropic functions of teleosts and amphibians.

PMID- 18343024
TI  - Guggulsterone, a plant sterol, inhibits NF-kappaB activation and protects
      pancreatic beta cells from cytokine toxicity.
AB  - Guggulsterone has been used to treat hyperlipidemia, arthritis, and obesity.
      Although its anti-inflammatory and anti-hyperlipidemic effects have been well
      documented, the effect of guggulsterone on pancreatic beta cells is unknown.
      Therefore, in this study, the effect of guggulsterone on IL-1beta- and IFN-gamma
      induced beta-cell damage was investigated. Treatment of RINm5F (RIN) rat
      insulinoma cells with IL-1beta and IFN-gamma induced cell damage, and this damage
      was well correlated with nitric oxide (NO) and prostaglandin E2 (PGE2)
      production. However, guggulsterone completely prevented cytokines-mediated
      cytotoxicity, as well as NO and PGE2 production, and these effects were
      correlated with reduced levels of the inducible form of NO synthase (iNOS) and
      cyclooxygenase-2 (COX-2) mRNA and protein expressions. The molecular mechanism by
      which guggulsterone inhibits iNOS and COX-2 gene expressions appeared to involve
      the inhibition of NF-kappaB activation. The cytoprotective effects of
      guggulsterone were also mediated through the suppression of the JAK/STAT pathway.
      Cells treated with the cytokines downregulated the protein level of SOCS-3,
      however pretreatment with guggulsterone attenuated this decrease. Additionally,
      in a second set of experiments in which rat islets were used, the findings
      regarding the beta-cell protective effects of guggulsterone were essentially the
      same as those observed when RIN cells were used; guggulsterone prevented
      cytokines-induced NO and PGE2 production, iNOS and COX-2 expressions, JAK/STAT
      activation, NF-kappaB activation, downregulation of SOCS-3, and impairment of
      glucose-stimulated insulin secretion. Collectively, these results suggest that
      guggulsterone may be used to preserve functional beta-cell mass.

PMID- 18343025
TI  - GATA-4 upregulates glucose-dependent insulinotropic polypeptide expression in
      cells of pancreatic and intestinal lineage.
AB  - A thorough examination of glucose-dependent insulinotropic polypeptide (GIP)
      expression has been hampered by difficulty in isolating widely dispersed, GIP
      producing enteroendocrine K-cells. To elucidate the molecular mechanisms
      governing the regulation of GIP expression, 14 intestinal and pancreatic cell
      lines were assessed for their suitability for studies examining GIP expression.
      Both STC-1 cells and the pancreatic cell line betaTC-3 were found to express GIP
      mRNA and secrete biologically active GIP. However, levels of GIP mRNA and
      bioactive peptide and the activity of transfected GIP reporter constructs were
      significantly lower in betaTC-3 than STC-1 cells. When betaTC-3 cells were
      analyzed for transcription factors known to be important for GIP expression, PDX
      1 and ISL-1, but not GATA-4, were detected. Double staining for GIP-1 and GATA-4
      in mouse duodenum demonstrated GATA-4 expression in intestinal K-cells. Exogenous
      expression of GATA-4 in betaTC-3 cells led to marked increases in both GIP
      transcription and secretion. Lastly suppression of GATA-4 via RNA interference,
      in GTC-1 cells, a subpopulation of STC-1 cells with high endogenous GIP
      expression resulted in a marked an attenuation of GIP promoter activity. Our data
      support the hypothesis that GATA-4 may function to augment or enhance GIP
      expression rather than act as an initiator of GIP transcription.

PMID- 18343026
TI  - Kaempferol-7-O-beta-D-glucoside (KG) isolated from Smilax china L. rhizome
      induces G2/M phase arrest and apoptosis on HeLa cells in a p53-independent
      manner.
AB  - Kaempferol-7-O-beta-D-glucoside (KG), a flavonoid glycoside, isolated from Smilax
      china L. rhizome, displayed marked anticancer activity on a panel of established
      cancer cells, of which, HeLa human cervix carcinoma cells were the most
      sensitive. Meanwhile, the cytotoxic effects of KG on normal human cells (HEK293
      embryonic kidney cells and L-02 embryonic liver cells) were much smaller than on
      cancer cells. This work studied the molecular mechanisms underlying KG induced
      growth inhibition in HeLa cells. The results showed that KG induced G2/M phase
      growth arrest correlated with Cyclin B1 and Cdk1 decrease in a p53-independent
      manner, and also caused an increase in apoptosis, which was confirmed by
      characteristic morphological changes, evident DNA fragmentation, increased
      apoptotic sub-G1 population. Furthermore, inhibition of NF-kappaB nuclear
      translocation, up-regulation of Bax and down-regulation of Bcl-2, were observed
      in HeLa cells treated with KG, which indicated that the mitochondrial pathway was
      involved in the apoptosis signal pathway. In summary, KG displayed a significant
      anti-tumor effect through cell cycle arrest and apoptotic induction in HeLa
      cells, which suggested that KG might have therapeutic potential against cervix
      carcinoma.

PMID- 18343027
TI  - Celastrol inhibits the growth of human glioma xenografts in nude mice through
      suppressing VEGFR expression.
AB  - Celastrol, a compound purified from Tripterygium wilfordii whose preparations
      have been used for clinical treatment for rheumatoid arthritis, has been
      demonstrated to have antiangiogenic activity, and be inhibitory against mice
      tumor growth by a few recent studies. However, whether its antiangiogenic
      activity plays a role in the celastrol-mediated suppression of tumor growth and
      the molecular basis of anti-tumor activity are poorly understood. In this study,
      we found that celastrol inhibited the growth of human glioma xenografts in mice,
      which concurred with the suppression of angiogenesis. Interestingly, while
      celastrol had no effect on either the expression of VEGF or its mRNA levels,
      celastrol treatment lowered the expression levels of its receptors (VEGFR-1 and
      VEGFR-2) and their mRNA levels. These findings suggest that celastrol have
      potential to be used as an antiangiogenesis drug through its role in suppressing
      VEGF receptors expression that might consequently reduce the signal transduction
      between VEGF and VEGFR.

PMID- 18343028
TI  - Isolation and characterization of cancer stem cells from a human glioblastoma
      cell line U87.
AB  - A variety of malignant cancers have been found to contain a subpopulation of stem
      cell-like tumor cells, or cancer stem cells (CSCs). However, the existence of
      CSCs in U87, a most commonly used glioma cell line, is still controversial. In
      this study, we demonstrate that U87 cell line contained a fraction of tumor cells
      that could form tumor spheres and were enriched by progressively increasing the
      concentration of serum-free neural stem cell medium with or without low dose
      vincristine. These cells possessed the ability of self-renewal and multipotency,
      the defined characteristics of CSCs. Moreover, the tumors formed by the secondary
      spheres displayed typical histological features of human glioblastoma, including
      cellular pleomorphism, pseudopalisades surrounding necrosis, hyperchromatic
      nuclei, high density of microvessels and invasion to the brain parenchyma. These
      results indicate that gradually increasing the concentration of serum-free neural
      stem cell culture medium with or without vincristine is a simple and effective
      method for isolation of CSCs to study the initiation and progression of human
      glioblastoma.

PMID- 18343029
TI  - Bcl-2 overexpression attenuates SP600125-induced apoptosis in human leukemia U937
      cells.
AB  - SP600125 is a specific inhibitor of c-Jun N-terminal kinase (JNK) that is known
      to strongly induce apoptosis and block cell cycle progression in G2/M phase. In
      this study, we demonstrated that treatment of U937 cells with SP600125 resulted
      in significant G2/M cell cycle arrest that was due to decreased cyclin B1 and
      cdc25c protein levels. Moreover, SP600125 promoted LDH release and DNA
      fragmentation that was associated with caspase-3 activation and degradation of
      its substrates. In contrast, overexpression of the antiapoptotic protein Bcl-2
      rendered leukemia cells resistant to SP600125-induced apoptosis, but more
      sensitive to G2/M phase arrest and endoreduplication (>4N DNA). Overexpression of
      Bcl-2 significantly inhibited SP600125-induced caspase-3 activation and
      degradation of its substrates, and sustained expression levels of the IAP-2
      proteins following SP600125 treatment. The inhibitory effect of Bcl-2 on
      apoptosis was attenuated by treatment with the small molecule Bcl-2 inhibitor,
      HA14-1. These data provide important mechanistic insights related to Bcl-2
      mediated resistance to SP600125-induced apoptosis, and induction of G2/M phase
      arrest and endoreduplication.

PMID- 18343030
TI  - Equilibrium, kinetic and sorber design studies on the adsorption of Aniline blue
      dye by sodium tetraborate-modified Kaolinite clay adsorbent.
AB  - Raw Kaolinite clay obtained Ubulu-Ukwu, Delta State of Nigeria and its sodium
      tetraborate (NTB)-modified analogue was used to adsorb Aniline blue dye. Fourier
      transformed infrared spectra of NTB-modified Kaolinite suggests that modification
      was effective on the surface of the Kaolinite clay with the strong presence of
      inner -OH functional group. The modification of Kaolinite clay raised its
      adsorption capacity from 1666 to 2000 mg/kg. Modeling adsorption data obtained
      from both unmodified and NTB-modified Kaolinite clay reveals that the adsorption
      of Aniline blue dye on unmodified Kaolinite clay is on heterogeneous adsorption
      sites because it followed strongly the Freundlich isotherm equation model while
      adsorption data from NTB-modified Kaolinite clay followed strongly the Langmuir
      isotherm equation model which suggest that Aniline blue dye was adsorb
      homogeneous adsorption sites on the NTB-modified adsorbent surface. There was an
      observed increase in the amount of Aniline blue adsorbed as initial dye
      concentration was increased from 10 to 30 mg/L. It was observed that kinetic data
      obtained generally gave better robust fit to the second-order kinetic model
      (SOM). The initial sorption rate was found to increased with increasing initial
      dye concentration (from 10 to 20 mg/L) for data obtained from 909 to 1111 mg kg(
      1)min(-1) for unmodified and 3325-5000 mg kg(-1) min(-1) for NTB-modified
      adsorbents. Thereafter there was a decrease in initial sorption rate with further
      increase in dye concentration. The linearity of the plots of the pseudo-second
      order model with very high-correlation coefficients indicates that chemisorption
      is involved in the adsorption process. From the design of a single-batch adsorber
      it is predicted that the NTB-modified Kaolinite clay adsorbent will require 50%
      less of the adsorbent to treat certain volumes of wastewater containing 30 mg/L
      of Aniline blue dye when it is compared with the unmodified adsorbent. This will
      be cost effective in the use of NTB-modified adsorbent for the adsorption of
      Aniline blue dye from water and wastewater.

PMID- 18343031
TI  - Detection of amyloid beta protein in the urine of Alzheimer's disease patients
      and healthy individuals.
AB  - To seek for a new valid biomarker using non-invasive specimens for the diagnosis
      of Alzheimer's disease (AD) and mild cognitive impairment (MCI), we carried out
      the detection of amyloid beta (Abeta) protein in urine. Ten-millilitre urine
      samples were first sedimented with trichloroacetic acid, and the pellets were
      resuspended for further analysis by Western blotting with anti-Abeta antibody.
      The detection sensitivity of the method was 40pg/ml. Rates of subjects positive
      for monomeric Abeta according to their clinical dementia rating (CDR) were 11.1%
      for CDR 0, 62.5% for CDR 0.5, 83.3% for CDR 1, 54.5% for CDR 2 and 0% for CDR 3.
      A single Abeta band relative to the CDR score reflects an alteration in the
      production, solubility and clearance of Abeta in the brain. Thus, the method
      could be used as both a diagnostic and monitoring tool in assessing AD and MCI
      patients during disease-modifying therapies.

PMID- 18343032
TI  - Contribution of P2Y(1) receptors to ADP signalling in mouse spinal cord cultures.
AB  - Mixed neuronal and glial cell spinal cord cultures from neonates express ADP
      sensitive P2Y(1,12&13) receptors. ADP (10microM) evoked increases in
      intracellular calcium that were essentially abolished by the P2Y(1) receptor
      antagonist MRS2179 (10microM), responses were also absent in preparations from
      P2Y(1) receptor deficient mice however UTP (100microM) evoked calcium rises were
      unaffected. ADP also evoked a robust increase in extracellular signal-regulated
      protein kinase (ERK) phosphorylation that was of similar magnitude in the
      cultures from wild type and P2Y(1) receptor deficient mice. These results suggest
      that ADP acts through P2Y(1) receptors to mediate an increase in intracellular
      calcium but not to stimulate ERK phosphorylation in the spinal cord.

PMID- 18343033
TI  - A review of the evidence against the "first come first served" hypothesis.
      Comment on Truini et al. [Pain 2007;131:43-7].

PMID- 18343034
TI  - Antinociceptive profile of ring A-reduced progesterone metabolites in the
      formalin test.
AB  - The present study investigated the effect of acute systemic administration of six
      progesterone metabolites on formalin-induced pain in the rat. The 3alpha
      hydroxylated metabolites allopregnanolone and pregnanolone are highly potent
      positive modulators at the GABA(A) receptor and produced a biphasic effect on
      pain in the formalin test. Dose-dependent antinociception was observed at lower
      doses (maximal antinociception at 0.16mg/kg) and was reversed at higher doses.
      Bicuculline abolished the antinociceptive effect. The 3beta-hydroxylated
      epipregnanolone and isopregnanolone are inactive or only weekly active at the
      GABA(A) receptor, and did not affect formalin-induced pain. 5alpha- and 5beta
      dihydroprogesterone have also been shown to have low affinity for the GABA(A)
      receptor, but can be rapidly metabolized to their 3alpha-hydroxylated
      counterparts. In the formalin test, they produced a biphasic effect on pain
      similar to that of pregnanolone and allopregnanolone, but with lower potency. The
      effect was reversible by bicuculline, showing involvement of the GABA(A)
      receptor, and was blocked by indomethacin, implying that the antinociceptive
      effect is dependent on their conversion to allopregnanolone or pregnanolone. The
      results indicate that GABA-ergic progesterone metabolites modulate nociception. A
      change in levels of GABA-ergic progesterone metabolites, such as is observed in
      depression, chronic fatigue and premenstrual dysphoric disorder could, therefore,
      contribute to the pain complaints associated with these disorders.

PMID- 18343035
TI  - Changing patient perceptions of their illness: can they contribute to an improved
      outcome for episodes of musculoskeletal pain?

PMID- 18343036
TI  - Thermal nociception and TRPV1 function are attenuated in mice lacking the
      nucleotide receptor P2Y2.
AB  - Recent studies indicate that ATP and UTP act at G protein-coupled (P2Y)
      nucleotide receptors to excite nociceptive sensory neurons; nucleotides also
      potentiate signaling through the pro-nociceptive capsaicin receptor, TRPV1. We
      demonstrate here that P2Y(2) is the principal UTP receptor in somatosensory
      neurons: P2Y(2) is highly expressed in dorsal root ganglia and P2Y(2)-/- mice
      showed profound deficits in UTP-evoked calcium transients and potentiation of
      capsaicin responses. P2Y(2)-/- mice were also deficient in the detection of
      painful heat: baseline thermal response latencies were increased and mutant mice
      failed to develop thermal hypersensitivity in response to inflammatory injury
      (injection of complete Freund's adjuvant into the hindpaw). P2Y(2) was the only
      Gq-coupled P2Y receptor examined that showed an increase in DRG mRNA levels in
      response to inflammation. Surprisingly, TRPV1 function was also attenuated in
      P2Y(2)-/- mice, as measured by the frequency and magnitude of capsaicin responses
      in vitro and behavioral responses to capsaicin administration in vivo. However,
      TRPV1 mRNA levels and immunoreactivity were not reduced, and behavioral
      sensitivity to capsaicin could be largely restored in P2Y(2)-/- mice by
      pretreatment with bradykinin, suggesting that normal function of TRPV1 requires
      ongoing modulation by G protein-coupled receptors. These results indicate that
      nucleotide signaling through P2Y(2) plays a key role in thermal nociception.

PMID- 18343037
TI  - Role of ASIC3 in the primary and secondary hyperalgesia produced by joint
      inflammation in mice.
AB  - The acid sensing ion channel 3 (ASIC3) is critical for the development of
      secondary hyperalgesia as measured by mechanical stimulation of the paw following
      muscle insult. We designed experiments to test whether ASIC3 was necessary for
      the development of both primary and secondary mechanical hyperalgesia that
      develops after joint inflammation. We used ASIC3 -/- mice and examined the
      primary (response to tweezers) and secondary hyperalgesia (von-Frey filaments)
      that develops after joint inflammation comparing to ASIC3 +/+ mice. We also
      examined the localization of ASIC3 to the knee joint afferents innervating the
      synovium using immunohistochemical techniques before and after joint
      inflammation. We show that secondary mechanical hyperalgesia does not develop in
      ASIC3 -/- mice. However, the primary mechanical hyperalgesia of the inflamed knee
      joint still develops in ASIC3 -/- mice and is similar to ASIC3 +/+ mice. In knee
      joint synovium from ASIC3 +/+ mice without joint inflammation, ASIC3 was not
      localized to joint afferents that were stained with an antibody to protein gene
      product (PGP) 9.5 or calcitonin gene-related peptide (CGRP). ASIC3 was found,
      however, in synoviocytes of the knee joint of uninflamed mice. In ASIC3 +/+ mice
      with joint inflammation, ASIC3 co-localized with PGP 9.5 or CGRP in joint
      afferents innervating the synovium. We conclude that the decreased pH that occurs
      after inflammation would activate ASIC3 on primary afferent fibers innervating
      the knee joint, increasing the input to the spinal cord resulting in central
      sensitization manifested behaviorally as secondary hyperalgesia of the paw.

PMID- 18343038
TI  - Infectivity, pathogenicity, and genetic characteristics of mammalian gastric
      Cryptosporidium spp. in domestic ruminants.
AB  - Farm ruminants were infected experimentally with four mammalian gastric
      Cryptosporidium, namely Cryptosporidium andersoni LI03 originated from cattle and
      three isolates of Cryptosporidium muris from brown rat (isolate RN66), Bactrian
      camel (isolate CB03) and firstly characterized isolate from East African mole rat
      (isolate TS03). Sequence characterizations of the small-subunit rRNA gene showed
      that the LI03 isolate was C. andersoni and the other three isolates belonged to
      C. muris, although the TS03 isolate showed unique sequence variations (one single
      nucleotide change and four nucleotide insertions). C. andersoni LI03 was
      infectious for calves only, whereas lambs and kids were susceptible to C. muris
      CB03. C. muris TS03 and RN66 were not infectious for any farm ruminants.
      Infection dynamics including prepatent and patent period and infection intensity
      of the isolates used differed depending on the host species, but no clinical
      signs of cryptosporidiosis were observed in any of experimentally infected hosts.
      Cryptosporidium developmental stages were only detected in infected animals in
      the abomasum region. Histopathological changes were characterized by dilatation
      and epithelial metaplasia of infected gastric glands with no significant
      inflammatory responses in the lamina propria.

PMID- 18343039
TI  - Testosterone and gonadotropins but not estrogen associated with spatial ability
      in women suffering from schizophrenia: a double-blind, placebo-controlled study.
AB  - The aim of this study was to investigate the association between estrogen and
      spatial ability tasks in women suffering from schizophrenia. For this purpose, a
      placebo-controlled, double-blind, three-time cross-over study using 17beta
      estradiol combined with norethisterone acetate for replacement therapy and as an
      adjunct to a naturalistic maintenance antipsychotic treatment was carried out
      over a period of 8 months. Nineteen women (mean age=38.0 years, SD=9.9 years)
      with schizophrenia hospitalized for the first time or repeatedly were included in
      the study. Sex hormones - 17beta-estradiol, luteinizing hormone (LH), follicle
      stimulating hormone (FSH), prolactin, testosterone, and dehydroepiandrosterone
      sulfate - were measured and the patients completed a neuropsychological test in
      the last two active drug and/or placebo phases. Three different spatial ability
      tasks - spatial orientation, spatial visualization, and flexibility of closure -
      were measured by a paper-and-pencil test. No association between estrogen and
      spatial ability was found; however, in an additional exploratory data analysis,
      high levels of testosterone, LH, and FSH correlated significantly with
      performance in the flexibility of closure task. This is the very first study,
      based on estrogen intervention instead of physiological hormone changes, to
      examine the association between estrogen and spatial ability in women with
      schizophrenia.

PMID- 18343040
TI  - Predictors of involvement in the juvenile justice system among psychiatric
      hospitalized adolescents.
AB  - OBJECTIVE: Several risk factors for juvenile justice involvement have been
      identified in previous research among delinquents and include mental illness,
      substance use, trauma and abuse, family dysfunction, poor parenting, school
      problems, and aggressive behavior. However, most of these predictors resulted
      from studies among adolescents incarcerated in the juvenile justice system. We
      were interested in finding out the prevalence rates of juvenile justice
      involvement among psychiatric inpatient adolescents and determining predictors of
      juvenile justice involvement in this high-risk group. METHODS: Six hundred and
      thirty-six medical records from adolescents ages 12-17 years who were
      consecutively admitted to one of two psychiatric inpatient units between July 1,
      2003 and June 30, 2004 were examined. RESULTS: Almost half (43.6%) of
      hospitalized adolescents had a history of juvenile justice involvement. Logistic
      regression analysis was conducted to determine predictors of juvenile justice
      involvement. Significant predictors of juvenile justice involvement included
      being male, parental legal history, family substance abuse history, disruptive
      disorder, cocaine use, being sexually active, and having a history of aggressive
      behavior. CONCLUSIONS: Adolescents in mental health or substance abuse treatment
      settings should be screened for juvenile justice involvement and appropriate
      referrals made to prevent worsening problems for at-risk youth.

PMID- 18343041
TI  - The influence of attitudes, acculturation, and gender on substance use for
      Mexican American middle school students.
AB  - The present study tested if current drug use was related to acculturation
      (measured by language spoken at home), gender, or youth attitudes towards drugs
      in a large sample of 8th grade, predominantly Mexican American, Hispanic youth.
      The data were obtained via self-report survey from 2964 Hispanic youth in 108
      schools. Hierarchical linear modeling (HLM) was used to test if acculturation,
      gender, or youth attitudes towards drugs predicted past 30-day use of alcohol,
      inhalant, or marijuana use and assess school-level influences. Acculturation and
      gender interacted with attitudes towards drugs to predict current alcohol use.
      Gender interacted with attitudes towards drugs to predict current alcohol and
      inhalant use. Having positive attitudes towards drugs was related to increased
      substance use for all three drug types. Hispanic eighth grade girls had
      significantly higher use rates than boys for both alcohol and inhalants.
      Additional research is needed to better understand the influence of acculturation
      on substance use among Hispanic youth.

PMID- 18343042
TI  - A broken BDNF hypothesis.

PMID- 18343043
TI  - Could calcitonin be a useful therapeutic agent for trigeminal neuralgia?
AB  - Trigeminal neuralgia (TN) has been recognized as one of the most common
      neurovascular syndromes caused by the vascular contact of the trigeminal nerve in
      its root entry zone (REZ) with a branch of the superior or anterior inferior
      cerebellar arteries, leading to a demyelinization of trigeminal sensory fibers
      within either the nerve root or, less commonly, the brainstem. There is a lack of
      certainty regarding the aetiology and pathophysiology of TN, therefore the
      treatment of trigeminal neuropathic pain disorders continues to be a major
      therapeutic challenge. The identification of novel therapeutic agents for the
      treatment of these disorders is important. Calcitonin (especially intranasal)
      provides an interesting analgesic effect in a series of painful conditions
      including reflex sympathetic dystrophy syndrome, adhesive capsulitis, ankylosing
      spondylitis, rheumatoid arthritis, vertebral crush fractures and metastasis,
      phantom limb pain, etc. Exogenous calcitonin is thought to cross the blood-brain
      barrier and to accumulate slowly in the brain, inducing analgesia once sufficient
      receptors are occupied. We hypothesize that calcitonin may has anti - trigeminal
      neuralgia properties. From the clinical point of use, the analgesic effect of
      calcitonin will be beneficial throughout the whole period of medical treatment of
      trigeminal neuralgia patients.

PMID- 18343044
TI  - Intestinal protozoa are hypothesized to stimulate immunosurveillance against
      colon cancer.
AB  - Colon cancer in humans results in considerable morbidity and mortality throughout
      most of the world. During the twentieth century, there was a rapid rise in colon
      cancer within modernizing countries that has not been adequately explained,
      although the role of diet has been widely explored. Previously, we showed that
      the presence of the endemic Eimeria spp. protozoan in intestinal tissues is
      associated with regions of low tumorigenesis in the large and small bovine
      intestine and that an Eimeria surface protein is a potent activator of dendritic
      cells and a useful immunomodulator, with anti-cancer and anti-viral properties.
      Therefore, we hypothesize that the persistent presence of such an intestinal
      protozoan enhances immunosurveillance by elevating the intestinal alert status
      and that the loss of these organisms could lead to a higher incidence of colon
      cancer. Preliminary support of this hypothesis derives from the observations that
      domestic animals, known to maintain this protozoan, have very low colon cancer
      incidence. We propose that this also may occur in human populations that use
      human excrement (night soil) as a fertilizer, a practice that serves to complete
      the life cycle of this type of microbe. We examine some evidence for this
      hypothesis in Japan's mortality patterns, where we show that colon cancer
      increased after the cessation of night soil use, but before the change to a
      western diet. We conclude that this hypothesis, a variation of the hygiene
      hypothesis, is worth further consideration and continued elaboration.

PMID- 18343045
TI  - Breast cancer screening among Chamorro women in California.
AB  - BACKGROUND: This study evaluated breast cancer-related knowledge, attitudes and
      behaviors among Chamorros in San Diego, California and compared mammogram use
      between those affiliated with the military and others. METHODS: A survey was
      administered to 110 self-reported Chamorro women. Inclusion criteria included
      being self-reported Chamorro woman >40 years with no history of breast cancer.
      Approximately equal proportions of participants with (52%) and without (48%)
      military affiliation were recruited to test the assumption that use of
      mammography differed between the two groups. Descriptive statistics and bivarate
      analyses were conducted. RESULTS: Of the 110 respondents, 42% had at least some
      college education, 41% had household incomes of at least $50,000, and 87%
      reported having health insurance. Approximately 93% reporting ever having a
      mammogram and 75% reported having it within the past 2 years. The difference
      between mammography use among women with and without military affiliation was not
      significant (85% versus 72%; p=0.11). However, women with military insurance
      (95%) were more likely than others (74%) to have had a mammogram within that time
      frame (p=.05). Other factors associated with higher mammography use included
      reporting better access to medical care (p=.03), receiving a recommendation for
      mammography from a health care provider (p=.002), and knowledge that cancer can
      be cured if detected early (p=.01) and that women should get a mammogram yearly
      (p=.01). CONCLUSION: Chamorro women in San Diego have relatively high rates of
      mammography use. This finding may be due, in part, to the relatively high rates
      of health insurance coverage (particularly military insurance) among these women.

PMID- 18343046
TI  - Reducing cancer health disparities: perspective of the National Cancer Institute.
AB  - BACKGROUND: The National Cancer Institute created the Special Population Network
      (SPN) to develop cancer awareness, research and training with partnerships from
      community and research organizations. METHODS: Eighteen SPNs were funded with the
      goals of enlisting community partnerships, enhancing training opportunities for
      minority scientists, and conducting pilot research projects. RESULTS: The SPN
      program concluded in 2005 after achieving many major milestones. CONCLUSION: This
      paper provides background information about the SPN and one of its programs, the
      Pacific Islander Cancer Control Network.

PMID- 18343047
TI  - [Antibiotics susceptibility of Streptococcus and Enterococcus: data of Onerba
      network].
AB  - This work was aimed to analyze trends in susceptibility to antibiotics among the
      main species of beta-hemolytic streptococci involved in community-acquired
      infections in human (Streptococcus pyogenes and Streptococcus agalactiae), or in
      animals (Streptococcus suis and Streptococcus uberis) and also among the main
      enterocci species, Enterococcus faecalis and Enterococcus faecium. Data were
      recorded since 1996 through the Onerba networks. S. pyogenes, as the other beta
      hemolytic streptococci studied remained fully susceptible to beta-lactam
      antibiotics. However, susceptibility to macrolides is clearly decreasing in S.
      pyogenes. In 2002, only 62 to 65% of the strains according to the network
      considered, were susceptible to erythromycin. A similar trend was observed for S.
      agalactiae with only 75% of erythromycin susceptibility in 2002, and for both
      species isolated from animals S. suis and S. uberis, with respectively 35 and 76%
      of strains susceptible to erythromycin. In enterococci, susceptibility to beta
      lactams remained stable between 2000 and 2004. Indeed, the susceptibility to
      aminopenicillins remained high in E. faecalis (about 98%), whereas the proportion
      of E. faecium isolates susceptible to these antibiotics were lower than 60%. From
      1999 to 2004, various studies conducted in French hospitals showed that the
      vancomycin resistance among enterococci accounted for less than 2%. However, the
      recent emergence of glycopeptide resistant enterococci clusters in French
      hospitals is a matter of concern and emphasizes the need for an ongoing
      surveillance. Such trend in macrolide resistance among S. pyogenes or S.
      agalactiae should consequently lead to propose other alternatives in case of beta
      lactam allergy, and for pharyngitis, to rethink the place of the culture for
      susceptibility testing.

PMID- 18343048
TI  - Contextual fear conditioning differs for infant, adolescent, and adult rats.
AB  - Contextual fear conditioning was tested in infant, adolescent, and adult rats in
      terms of Pavlovian-conditioned suppression. When a discrete auditory-conditioned
      stimulus (CS) was paired with footshock (unconditioned stimulus, US) within the
      largely olfactory context, infants and adolescents conditioned to the context
      with substantial effectiveness, but adult rats did not. When unpaired
      presentations of the CS and US occurred within the context, contextual fear
      conditioning was strong for adults, weak for infants, but about as strong for
      adolescents as when pairings of CS and US occurred in the context. Nonreinforced
      presentations of either the CS or context markedly reduced contextual fear
      conditioning in infants, but, in adolescents, CS extinction had no effect on
      contextual fear conditioning, although context extinction significantly reduced
      it. Neither CS extinction nor context extinction affected responding to the CS
      context compound in infants, suggesting striking discrimination between the
      compound and its components. Female adolescents showed the same lack of effect of
      component extinction on response to the compound as infants, but CS extinction
      reduced responding to the compound in adolescent males, a sex difference seen
      also in adults. Theoretical implications are discussed for the development of
      perceptual-cognitive processing and hippocampus role.

PMID- 18343049
TI  - Surface irregularity induced-tunneling behavior of the formosan subterranean
      termite.
AB  - Subterranean termites forage from place to place by tunneling through soil. In
      order to examine termite-tunneling responses to external factors, we designed a
      square arena that contains five introduction chambers connected with narrow
      paths, which was filled with sand. Triangle-shaped indentation with width W and
      height H was provided as surface irregularity on the sand facing the introduction
      chambers by using templates. After termites were introduced into the chambers, we
      measured elapsed time, tau, for a tunnel to reach the point at 3 mm away from the
      apex of the irregularity. We found that for W=0 mm (the absence of irregularity),
      termites (Coptotermes formosanus Shiraki) did not tunnel for approximately 7h,
      whereas, for W=1, 2, 3, and 4 mm, they exhibited the tunneling behavior within 20
      min. The result indicated that the presence of surface irregularity is essential
      to induce termite tunneling. In addition, we found that W was correlated with
      tau, whereas H did not influence tau. This was briefly discussed in the context
      of individual movement behavior.

PMID- 18343050
TI  - Further evidence of an association between adolescent bipolar disorder with
      smoking and substance use disorders: a controlled study.
AB  - Although previous work suggests that juvenile onset bipolar disorder increases
      risk for substance use disorders and cigarette smoking, the literature on the
      subject is limited. We evaluated the association of risk for substance use
      disorders and cigarette smoking with bipolar disorder in adolescents in a case
      control study of adolescents with bipolar disorder (n=105, age 13.6+/-2.5 years
      [mean]; 70% male) and without bipolar disorder ("controls"; n=98, age 13.7+/-2.1
      years; 60% male). Rates of substance use and other disorders were assessed with
      structured interviews (KSADS-E for subjects younger than 18, SCID for 18-year-old
      subjects). Bipolar disorder was associated with a significant age-adjusted risk
      for any substance use disorder (hazard ratio[95% confidence interval]=8.68[3.02
      25.0], chi(2)=16.06, p<0.001, df=1), alcohol abuse (7.66 [2.20 26.7],
      chi(2)=10.2, p=0.001, df=1), drug abuse (18.5 [2.46 139.10], chi(2)=8.03,
      p=0.005, df=1) and dependence (12.1 [1.54 95.50], chi(2)=5.61, p=0.02, df=1), and
      cigarette smoking (12.3 [2.83 53.69], chi(2)=11.2, p<0.001, df=1), independently
      of attention deficit/hyperactivity disorder, multiple anxiety, and conduct
      disorder (CD). The primary predictor of substance use disorders in bipolar youth
      was older age (BPD-SUD versus BPD+SUD, logistic regression: chi(2)=89.37,
      p<0.001). Adolescent bipolar disorder is a significant risk factor for substance
      use disorders and cigarette smoking, independent of psychiatric comorbidity.
      Clinicians should carefully screen adolescents with bipolar disorder for
      substance and cigarette use.

PMID- 18343051
TI  - Effects of a universal classroom behavior program in first and second grades on
      young adult problem outcomes.

PMID- 18343052
TI  - Endemic asthma inhaler abuse among antisocial adolescents.
AB  - BACKGROUND: Approximately 40 million prescriptions were dispensed in the U.S. for
      asthma inhalers in 2006. Although the pervasive distribution of asthma inhalers
      warrants greater attention to possible misuse of these products, few
      investigations have examined asthma inhaler misuse. The purpose of this study was
      to describe the prevalence, correlates and consequences of asthma inhaler misuse
      among antisocial youth. METHOD: A cross-sectional survey with face-to-face
      interviews assessing substance use, psychiatric symptoms, and antisocial
      behaviors among adolescents (N=723) in residential treatment. RESULTS: More than
      26% (N=193) of youth were diagnosed with asthma; 91.2% of asthmatic youth had
      received a prescription for an inhaler. Of the 373 youth who had used a
      prescribed or non-prescribed asthma inhaler, 23.6% (N=88) reported using an
      inhaler to get high (i.e., were inhaler misusers). Asthma inhaler misusers had an
      earlier onset of antisocial conduct, significantly greater levels of current
      psychiatric distress and lifetime suicidality, higher rates of lifetime substance
      use problems and volatile solvent abuse, and significantly higher levels of
      temperamental impulsivity and fearlessness than did inhaler non-users or users.
      Caucasian racial status, current level of psychiatric distress, and lifetime
      volatile solvent abuse significantly distinguished lifetime asthma inhaler users
      and misusers in multivariate logistic regression analyses. Asthma inhaler
      misusers were significantly more likely to report euphoria, memory problems,
      slurred speech, blurred vision, confusion, dizziness, and a variety of other
      acute reactions to asthma inhaler use than were asthma inhaler users.
      CONCLUSIONS: Asthma inhaler misuse for the purposes of getting high was prevalent
      among antisocial youth, co-occurred with other psychiatric and substance use
      problems, and was associated with adverse consequences.

PMID- 18343053
TI  - Mycobacterium avium subsp. paratuberculosis-specific mpt operon expressed in M.
      bovis BCG as vaccine candidate.
AB  - Mycobacterium (M.) avium subspecies paratuberculosis is the etiological agent of
      paratuberculosis (Johne's disease) in ruminants. Vaccination against
      paratuberculosis with an attenuated live vaccine has been shown not only to
      prevent or reduce disease symptoms but also to have severe side effects. In
      contrast, the tuberculosis vaccine strain M. bovis BCG is considered safe and the
      efficacy of vaccination with M. bovis BCG transformants carrying foreign antigens
      has been shown in several studies. The mpt genes of M. avium subsp.
      paratuberculosis are part of a putative pathogenicity island and have been
      described as possible virulence determinants. In this study we show that the mpt
      genes are transcribed on a single polycistronic mRNA in M. avium subsp.
      paratuberculosis. We cloned the entire mpt operon, transformed it into M. bovis
      BCG Pasteur using the integrative vector pMV306 and showed transcription and
      expression of the mpt genes in the M. bovis BCG transformant. In a challenge
      experiment with Balb/c mice we demonstrated that immunization with M. bovis BCG
      expressing the M. avium subsp. paratuberculosis-derived mpt operon significantly
      reduces amplification of M. avium subsp. paratuberculosis in liver and spleen of
      the host in comparison to both the mock-immunized animals as well as the M. bovis
      BCG-immunized control. These findings imply that immunization with M. bovis BCG
      transformants may constitute a new strategy in the development of an efficacious
      and safe vaccine against paratuberculosis.

PMID- 18343054
TI  - Sequence analysis of the protein-coding regions of foot-and-mouth disease virus
      O/HK/2001.
AB  - The nucleotide sequence of the protein-coding region of foot-mouth-disease virus
      (FMDV) strain O/HK/2001 was determined and compared with the sequences of other
      FMDVs that were registered in GenBank. The protein-coding region was 6966
      nucleotides in length and encoded a protein of 2322 amino acid residues.
      Comparison of the nucleotide sequence and its deduced amino acid sequence with
      those of other isolates indicated that O/HK/2001 belonged to the Cathay topotype.
      A genomic coding region nucleotide sequence phylogenetic tree of several FMDV-O
      isolates showed that O/HK/2001 was most closely related to FMDV isolates found in
      Taiwan during 1997, and especially shared significant similarity to HKN/2002,
      suggesting that the virus causing outbreaks in Hong Kong was genetically most
      closely related to that causing an outbreak of type O in Taiwan. Mutations in
      O/HK/2001 were revealed, including frequent substitutions in the VP1 and L
      proteins, and deletions involving 10 amino acid residues in the 3A protein. This
      study was undertaken to assess the regional variation of prevalent FMDV type O
      viruses and to establish a sequence database for FMDV molecular epidemiological
      investigation.

PMID- 18343055
TI  - Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human
      intestinal Caco-2 cells.
AB  - Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in
      Europe and North America. In human intestinal Caco-2 cells, DON activates the
      mitogen-activated protein kinases (MAPKs). We hypothesized a link between DON
      ingestion and intestinal inflammation, and used Caco-2 cells to assess the
      effects of DON, at plausible intestinal concentrations (250-10,000 ng/ml), on
      inflammatory mediators acting downstream the MAPKs cascade i.e. activation of
      nuclear factor-kappaB (NF-kappaB) and interleukin-8 (IL-8) secretion. In
      addition, Caco-2 cells were co-exposed to pro-inflammatory stimuli in order to
      mimic an inflamed intestinal epithelium. Dose-dependent increases in NF-kappaB
      activity and IL-8 secretion were observed, reaching 1.4- and 7.6-fold,
      respectively using DON at 10 microg/ml. Phosphorylation of inhibitor-kappaB
      (IkappaB) increased (1.6-fold) at DON levels <0.5 microg/ml. Exposure of Caco-2
      cells to pro-inflammatory agents, i.e. 25 ng/ml interleukin-1beta, 100 ng/ml
      tumor necrosis factor-alpha or 10 microg/ml lipopolysaccharides, activated NF
      kappaB and increased IL-8 secretion. Synergistic interactions between these
      stimuli and DON were observed. These data show that DON induces NF-kappaB
      activation and IL-8 secretion dose-dependently in Caco-2 cells, and this effect
      was accentuated upon pro-inflammatory stimulation, suggesting DON exposure could
      cause or exacerbate intestinal inflammation.

PMID- 18343056
TI  - Breast cancer risk in postmenopausal women using testosterone in combination with
      hormone replacement therapy.
AB  - OBJECTIVES: Testosterone supplementation can be considered as a treatment option
      for surgically postmenopausal women with a distressful low sexual desire
      disorder, while on oestrogen therapy with or without progestagens. The purpose of
      this study is to review the available clinical data on the impact of exogenous
      testosterone containing postmenopausal hormone therapy on breast cancer risk.
      METHODS: A literature search was done in MEDLINE (1969-July 2007) and in addition
      in EMBASE and Biosis (1990-July 2007) for original reports in English and French.
      Case reports and studies without a control group were excluded. RESULTS: No
      prospective randomized clinical trials were found. The five studies found (two
      case-control studies, two cohort studies and one retrospective observational
      study) showed inconsistent results. All studies had severe methodological
      limitations. Formulations and dosages used could be considered suboptimal.
      CONCLUSION: At present, there are no valid randomized or observational clinical
      studies that provide evidence that the addition of testosterone to conventional
      postmenopausal hormone therapy influences breast cancer risk.

PMID- 18343057
TI  - Prevalence of osteoporosis in middle Anatolian population using calcaneal
      ultrasonography method.
AB  - BACKGROUND: There are a few studies on the prevalence of osteoporosis in Turkey.
      Most of such studies have been performed using classical diagnostic methods.
      Quantitative calcaneal ultrasonography is a contemporary procedure used in the
      diagnosis of osteoporosis. OBJECTIVE: The aim of this study is to determine the
      prevalence of the osteoporosis and risk factors in middle Anatolian population
      aged more than 40, using quantitative calcaneal ultrasonography. SUBJECTS AND
      METHODS: The present study was carried out in rural and urban areas of primary
      health care units. Evaluation of skeletal status was based on calcaneal
      quantitative ultrasound measurement, carried out by the Sahara Clinical Bone
      Sonometer (Hologic Waltham, MA, USA). RESULTS: There were 1437 individuals, 866
      were females (60.3%) and 571 were males (39.7%), aged in between 40 and 89 years.
      Standardized prevalence rates using Segi's population were found to be 14.0% in
      total, 17.1% in female and 9.2% in male. Osteoporosis prevalence increased with
      increasing ages. The highest prevalence value was determined in the individuals
      older than 70 years of age. Osteoporosis was more common among women compared to
      men. Osteoporosis prevalence increased in consistent with a decrease in the
      amount of milk, yoghurt and cheese consumption. CONCLUSION: Based on current
      study, it is concluded that osteoporosis is an important health problem.
      Requiring health education about life styles (activity and nutrition) to avoid
      and even control osteoporosis.

PMID- 18343058
TI  - In situ gelling hydrogels for pharmaceutical and biomedical applications.
AB  - Since Wichterle et al. introduced hydrogels as novel materials possibly suitable
      for a variety of biomedical applications, hydrogel research has become a fast
      developing and exciting research field. The soft and hydrophilic nature of
      hydrogels makes them particularly suitable as protein delivery system or as cell
      entrapping scaffold in tissue engineering. Traditional hydrogels were formed by
      chemical crosslinking of water-soluble polymers or by polymerization (of
      mixtures) of water-soluble monomers. Because of incompatibility of these
      crosslinking methods with fragile molecules like pharmaceutical proteins and
      living cells, in recent years research interest has been focused on hydrogels
      that gel spontaneously under physiological conditions. In these systems, hydrogel
      formation occurs in situ, at the site of injection, without the aid of
      potentially toxic or denaturizing crosslinking agents. This review provides an
      overview of in situ gelling systems and their potential in biomedical
      applications. Both photopolymerizable as well as self-assembling hydrogels, based
      on either chemical crosslinks or physical interactions will be addressed.

PMID- 18343059
TI  - Lipid nanoparticles for prolonged topical delivery: an in vitro and in vivo
      investigation.
AB  - Dermal therapy is still a challenge due to the difficulties in controlling the
      active pharmaceutical ingredient (API) fate within the skin. Recently, lipid
      nanoparticles have shown a great potential as vehicle for topical administration
      of active substances, principally owing to the possible targeting effect and
      controlled release in different skin strata. Ketoprofen and naproxen loaded lipid
      nanoparticles were prepared, using hot high pressure homogenization and
      ultrasonication techniques, and characterized by means of photo correlation
      spectroscopy and differential scanning calorimetry. Nanoparticle behavior on
      human skin was assessed, in vitro, to determine drug percutaneous absorption
      (Franz cell method) and, in vivo, to establish the active localization (tape
      stripping technique) and the controlled release abilities (UVB-induced erythema
      model). Results demonstrated that the particles were able to reduce drug
      penetration increasing, simultaneously, the permeation and the accumulation in
      the horny layer. A prolonged anti-inflammatory effect was observed in the case of
      drug loaded nanoparticles with respect to the drug solution. Direct as well as
      indirect evidences corroborate the early reports on the usefulness of lipid
      nanoparticles as carriers for topical administration, stimulating new and deeper
      investigations in the field.

PMID- 18343060
TI  - Controlling granule size by granulation liquid feed pulsing.
AB  - The effects of inlet air humidity, granulation liquid feed rate and granulation
      liquid feed pulsing on the particle-size distribution of final granules were
      studied in a laboratory scale fluid-bed granulator using a central composite
      study design. The factors examined were modelled using three different particle
      size measurement techniques (sieve analysis, laser light diffraction and the
      spatial filtering technique). Best goodness of fit (R2=0.94) and goodness of
      prediction (Q2=0.90) values were obtained using particle-size results of the
      spatial filtering technique. Increasing inlet air humidity and granulation liquid
      feed rate resulted in greater median granule size, as expected. When pulsing
      (interruption of granulation liquid feed in predetermined sequences) was used,
      the median granule size decreased clearly. This effect was strong, especially
      with high inlet air humidity and rapid liquid feed rate processes. Granulation
      liquid feed pulsing is an effective way to modify the particle size of final
      granules. Pulsing can be used as a controlling tool to compensate for excessive
      moisture content in the granulation process.

PMID- 18343061
TI  - Thermodynamic studies of Fenbufen, Diflunisal, and Flurbiprofen: sublimation,
      solution and solvation of biphenyl substituted drugs.
AB  - Temperature dependency of saturated vapour pressure for Fenbufen (FBF) was
      obtained. Heat capacities for Fenbufen, Diflunisal (DIF), and Flurbiprofen (FBP)
      were measured, and standard thermodynamic functions of sublimation were
      calculated (FBF: DeltaGsub298=74.0 kJ mol(-1); DeltaHsub298=155.0+/-0.8 kJ mol(
      1); DeltaSsub298=272+/-3 J mol(-1)K(-1); DIF: DeltaGsub298=57.6 kJ mol(-1);
      DeltaHsub298=120.1+/-0.6 kJ mol(-1); DeltaSsub298=210+/-2 J mol(-1)K(-1); FBP:
      DeltaGsub298=53.3 kJ mol(-1); DeltaHsub298=110.2+/-0.5 kJ mol(-1);
      DeltaSsub298=191+/-2 J mol(-1)K(-1)). Thermochemical parameters of fusion process
      for FBF were obtained, and evaporation enthalpy was estimated from fusion and
      sublimation enthalpies. Temperature dependencies of the solubility in buffer
      solutions (pHs 2.0 and 7.4), n-Octanol, and n-Hexane were measured, and solution
      and solvation thermodynamic functions were calculated. The transfer thermodynamic
      functions from n-Hexane to solvents used (imitating specific "drug-solvent"
      interaction), and from buffer solutions to n-Octanol (imitating
      partitioning/distribution processes) were analyzed. Specific/non-specific "drug
      solvent" interaction ratios in terms of solvation enthalpies were estimated. All
      studied solutions are characterized by prevalence of non-specific "drug-solvent"
      interactions. A difference exists between mechanisms of partitioning and
      distribution of studied drugs.

PMID- 18343062
TI  - Penetrating multichannel stimulation and recording electrodes in auditory
      prosthesis research.
AB  - Microelectrode arrays offer the auditory systems physiologists many opportunities
      through a number of electrode technologies. In particular, silicon substrate
      electrode arrays offer a large design space including choice of layout plan,
      range of surface areas for active sites, a choice of site materials and high
      spatial resolution. Further, most designs can double as recording and stimulation
      electrodes in the same preparation. Scala tympani auditory prosthesis research
      has been aided by mapping electrodes in the cortex and the inferior colliculus to
      assess the CNS responses to peripheral stimulation. More recently silicon
      stimulation electrodes placed in the auditory nerve, cochlear nucleus and the
      inferior colliculus have advanced the exploration of alternative stimulation
      sites for auditory prostheses. Multiplication of results from experimental effort
      by simultaneously stimulating several locations, or by acquiring several streams
      of data synchronized to the same stimulation event, is a commonly sought after
      advantage. Examples of inherently multichannel functions which are not possible
      with single electrode sites include (1) current steering resulting in more
      focused stimulation, (2) improved signal-to-noise ratio (SNR) for recording when
      noise and/or neural signals appear on more than one site and (3) current source
      density (CSD) measurements. Still more powerful are methods that exploit closely
      spaced recording and stimulation sites to improve detailed interrogation of the
      surrounding neural domain. Here, we discuss thin-film recording/stimulation
      arrays on silicon substrates. These electrode arrays have been shown to be
      valuable because of their precision coupled with reproducibility in an ever
      expanding design space. The shape of the electrode substrate can be customized to
      accommodate use in cortical, deep and peripheral neural structures while flexible
      cables, fluid delivery and novel coatings have been added to broaden their
      application. The use of iridium oxide as the neural interface site material has
      increased the efficiency of charge transfer for stimulation and lowered impedance
      for recording electrodes.

PMID- 18343063
TI  - Comparative studies of the effects of Tabebuia avellanedae bark extract and beta
      lapachone on the hematopoietic response of tumour-bearing mice.
AB  - The effects of Tabebuia avellanedae (TACE), traditionally prescribed in the
      treatment of cancer, and the naphtoquinone beta-lapachone (beta-lap) on the
      growth and differentiation of granulocyte and macrophage progenitor cells (CFU
      GM) were studied in Ehrlich ascites tumour-bearing mice. Myelosuppression
      concomitant with increases in spleen CFU-GM and in serum colony-stimulating
      activity (CSA) were observed in these animals. Treatment with TACE (30-500 mg/kg)
      and beta-lap (1-5mg/kg) reversed these effects in a dose-dependent manner. The
      optimal biologically active doses of 120 mg/kg TACE and 1mg/kg beta-lap prolonged
      life span of tumour-bearing mice, both producing the same rate of extension in
      the duration of survival. Toxic manifestations were produced by the higher doses
      of beta-lap in normal and tumour-bearing mice. In spite of similarities between
      treatments, TACE concentrations used to treat the animals presented no traces of
      beta-lap, as measured by TLC and HPLC analyses. Our findings suggest that the
      antitumour effect of TACE and beta-lap, acting synergistically with other
      factors, such as specific cytokines, may result from enhanced macrophage
      activation against tumour cells. In addition, it is clear from our results that
      hematopoietic disorders produced by tumours are an important pathological
      condition that must be considered in drug development.

PMID- 18343064
TI  - Antidepressant effect of Yueju-Wan ethanol extract and its fractions in mice
      models of despair.
AB  - AIM OF THE STUDY: Yueju-Wan (YJ), a traditional Chinese medicinal formula, is
      commonly used for the treatment of depression-related syndromes in China. This
      study was conducted to evaluate the antidepressant activity of YJ ethanol extract
      (YJ-E) and its four different fractions, the petroleum ether fraction (YJ-EA),
      ethyl acetate fraction (YJ-EB), n-butanol fraction (YJ-EC) and final aqueous
      fraction (YJ-ED). MATERIALS AND METHODS: Two experimental despair animal models:
      the mice tail suspension test (TST) and the mice forced swimming test (FST) were
      used to evaluate the antidepressant activity of YJ-E and its fractions. These
      extracts or fractions were administered orally for 7 days, while the parallel
      positive control was given at the same time using fluoxetine hydrochloride (FLU)
      in TST and imipramine hydrochloride (IMI) in FST respectively. RESULTS: YJ-E high
      dose (YJ-E2), YJ-EA, YJ-EC and the positive control groups could decrease the
      duration of immobility in the TST and FST and have no significant changes in
      locomotor activity. YJ-E low dose (YJ-E1), YJ-EB, YJ-ED and the vehicle solvent
      (VEH) control group have no obvious effect on these same tests. CONCLUSIONS: In
      these despair animal models, YJ ethanol extract, the petroleum ether fraction and
      n-butanol fraction show potent antidepressant effects. The petroleum ether
      fraction and n-butanol fraction appear to be the active fractions of YJ-E.

PMID- 18343065
TI  - Reporting a fatality during tumescent liposuction.
AB  - Deaths of patients during elective surgery have drawn attention to the danger of
      anesthesia. Tumescent local anesthesia is subcutaneous infiltration of large
      volumes of dilute lidocaine with epinephrine to produce vasoconstriction while
      delivering anesthesia over large areas without lidocaine toxicity. This report
      documents the case of a 38-year-old woman who attended an outpatient clinic to
      undergo liposuction of the abdomen and bilateral hips and thighs. According to
      one witness, around 30 min after anesthesia administration, the victim suffered
      an episode of tonic-clonic convulsion. When the emergency medical services
      arrived the patient was in asystole. She died in spite of attempted
      cardiopulmonary resuscitation. The patient had no significant past medical
      history including no history of allergies or any known complications with
      anesthesia. A complete autopsy was performed and possible causes of death such as
      myocardial infarction, aspiration of food or foreign body, and pulmonary embolism
      were discarded. Anaphylactic shock was considered a possible but unlikely
      explanation for the fatality. Toxicological analyses revealed the presence of
      lidocaine and mepivacaine in heart blood, at concentrations of 4.9 and 16.2mg/L,
      respectively. All drugs involved in the case were detected using gas
      chromatography with nitrogen-phosphorus detector and confirmed using gas
      chromatography-mass spectrometry full scan mode after solid-phase extraction
      using Chem-Elut columns. An additional high-performance liquid chromatography
      coupled to diode-array detection screening also obtained the same results. Based
      on the autopsy findings, case history, and toxicology results, the forensic
      pathologists ruled that the cause of death was an overdose of local anesthetic
      agents. The Court of Law ruled the death as an involuntary homicide due to gross
      negligence.

PMID- 18343066
TI  - Transient encephalopathy with reversible white matter lesions: a case report.
AB  - We report on a boy with bilateral optic nerve hypoplasia and mild psychomotor
      retardation. At 1 year and 9 months of age, he was admitted to hospital with a
      cluster of febrile convulsions and unconsciousness. Magnetic resonance imaging
      (MRI) revealed widespread areas of high signal intensity on diffusion-weighted
      imaging of the deep cerebral white matter and corpus callosum. This imaging
      disappeared at five days of illness. No atrophy or abnormalities were noted on
      the 6-month follow-up MRI. Despite full recovery after the acute episode, the
      patient showed retarded developmental progress. We discuss the differential
      diagnosis for this case.

PMID- 18343067
TI  - [Sturge--Weber-Klippel--Trenaunay syndrome (case report)].
AB  - INTRODUCTION: Sturge-Weber syndrome is characterized by capillary malformations
      in the face, associated with leptomeningeal and choroidal venous malformations.
      Klippel-Trenaunay syndrome consists of the triad: capillary malformation of one
      leg, ipsilateral hypertrophy and varicose veins. OBSERVATION: We report the case
      of a 23-year-old male patient who presented a complex congenital neurocutaneous
      syndrome with vascular malformations involving the brain, face and limbs and
      associated with epilepsia and leptomeningeal calcifications. The patient
      fulfilled the diagnostic criteria of both vascular phacomatosis syndromes.
      DISCUSSION AND CONCLUSION: Similar descriptions of dual or overlapping syndromes
      have been published. Many show that there is no clear distinction between Klippel
      Trenaunay syndrome and Sturge-Weber syndrome. There is a clinical and biological
      overlap. The complexity of the disease phenotypes shows that a classification
      based on an eponymous category does not enable resolution of the nosological
      problems. Some authors suggest that these vascular malformations are best
      described in anatomical/histological or functional terms. We report a new
      observation that illustrates these difficulties.

PMID- 18343068
TI  - [Gastric calcifying fibrous pseudotumor, a rare mesenchymal tumor of the
      stomach].
AB  - We report a case of calcifying fibrous pseudotumor fortuitously discovered on
      abdominal CT-scan in a 50 year-old woman presenting with metrorragia. CT-scan
      showed a 2 cm hypodense nodular tumor of the gastric wall with granular
      calcifications. Upper endoscopy showed a nodular tumor along the lesser curvature
      of the gastric body, covered by normal gastric mucosa and biopsies were negative.
      A diagnosis of gastric stromal tumor was suspected and a partial gastrectomy was
      performed. On gross examination surgical specimen showed a firm, whitish nodular
      tumor measuring 2 cm in diameter. On microscopic examination the tumor was
      composed of whorls of dense hyalinized collagen bundles with a few fibroblasts.
      There were psammomatous calcifications and nodular aggregates of mononuclear
      inflammatory cells. Immunohistochemically, spindle cells stained for vimentin.
      They did not stain for smooth muscle actin, desmin, CD34, CD117, S100 protein, Ki
      67 and ALK-1. Surgical resection of the tumor was complete. Patient has no
      evidence of disease with a follow-up of 12 months. Only seven cases of gastric
      calcifiying fibrous pseudotumors have been reported in the literature. These
      benign tumors are usually incidentally discovered. They have characteristic
      imaging and microscopic features and appear as a distinct clinicopathologic
      entity different from stromal tumors.

PMID- 18343069
TI  - [Colonic lipoma: case report and literature review].
AB  - Colonic lipoma is a rare benign tumor infrequently met in clinical practice. We
      report a case of symptomatic lipoma of the ascending colon in a 61-year-old
      woman. Diagnosis was suspected on CT scan. Colotomy with lipectomy was performed.
      The diagnosis was confirmed by histological examination. Reviewing the literature
      and combining with our experience, we discuss the clinical features, diagnosis
      and treatment of this uncommon disease.

PMID- 18343070
TI  - [External radiotherapy and photodynamic therapy for esophageal carcinoma: a
      dangerous association?].
AB  - A 60-year-old man presented an oesophageal transmural necrosis fistulised in the
      trachea following curative photodynamic therapy (PDT) for a superficial
      recurrence of an oesophageal carcinoma, initially treated by radiochemotherapy.
      Two stents, a tracheal and an oesophageal one, were placed. Eight months later
      the patient is in complete remission with only mild swallowing problems. This
      complication, although unusual, has already been described by other teams with
      the association of radiochemotherapy and PDT. The present case study suggests
      that illumination dose should be lowered in this indication.

PMID- 18343071
TI  - MRI contrast media are used to improve visualization of abnormal structures or
      lesions in various parts of the body. Introduction.
AB  - Until recently it was believed that extracellular gadolinium based contrast
      agents (Gd-CA) were safe for both the kidneys and all other organs within the
      dose range up to 0.3mmol/kg body weight. However, in 2006, it was demonstrated
      that some Gd-CA may trig the development of nephrogenic systemic fibrosis, a
      generalized fibrotic disorder, in renal failure patients. This sub-section of
      European Journal of Radiology covers the current knowledge about NSF from many
      aspects. The prevention of NSF must be given high priority, but it should not
      lead to a denial of a well-justified, enhanced MRI examination with a stable
      agent.

PMID- 18343072
TI  - Extracellular gadolinium contrast agents: differences in stability.
AB  - Extracellular gadolinium contrast agents (Gd-CA) are either linear or macrocyclic
      chelates available as ionic or non-ionic preparations. The molecular structure
      whether cyclic or linear and ionicity determines the stability of Gd-CA. Linear
      chelates are flexible open chains which do not offer a strong binding to Gd(3+).
      In contrast, the macrocyclic chelates offer a strong binding to Gd(3+) by the
      virtue of being preorganized rigid rings of almost optimal size to cage the
      gadolinium atom. Non-ionic preparations are also less stable in comparison to the
      ionic ones as the binding between Gd(3+) with the negatively charged carboxyl
      groups is stronger in comparison to that with amides or alcohol in the non-ionic
      preparations. According to stability constants and kinetic measurements, the most
      stable Gd-CM is the ionic-macrocyclic chelate Gd-DOTA and the least stable agents
      are the non-ionic linear chelates gadodiamide and gadoversetamide. In vivo data
      confirmed the low stability of non-ionic linear chelates but no significant
      difference was observed amongst the macrocyclic agents whether ionic (Gd-DOTA) or
      non-ionic such as Gd-HP-DO3A and Gd-BT-DO3A. The stability of Gd-CA seems to be
      an important factor in the pathogenesis of the serious complication of
      nephrogenic systemic fibrosis. Gd-CA of low stability are likely to undergo
      transmetallation and release free Gd ions that deposit in tissue and attract
      circulating fibrocytes to initiate the process of fibrosis. No cases of NSF have
      been observed so far after the exclusive use of the stable macrocyclic Gd-CA.

PMID- 18343073
TI  - LC and LC-MS methods for the investigation of polypills for the treatment of
      cardiovascular diseases. Part 1. Separation of active components and
      classification of their interaction/degradation products.
AB  - "Polypill" is a fixed-dose combination (FDC) containing three or more drugs in a
      single pill. The same is under development for the treatment and prevention of
      cardiovascular diseases. In the present study, gradient LC methods were developed
      for simultaneous determination of the possible components of a polypill, i.e.,
      lisinopril, aspirin and one each among atenolol/hydrochlorothiazide and
      atorvastatin/simvastatin/pravastatin, in the presence of a total of 13 major
      interaction/degradation products. The drugs and the products were well separated
      using a reversed-phase (C-8) column and a mobile phase comprising of
      acetonitrile: phosphate buffer (pH 2.3). Other HPLC parameters were flow rate, 1
      ml/min; detection wavelength, 210 nm; column oven temperature, 60 degrees C; and
      injection volume, 5 microl. The methods were validated for linearity, precision,
      accuracy, and specificity. These were further modified to make them compatible
      for LC-MS studies by removal of the phosphate buffer and adjustment of pH by
      formic acid. The suitability of the methods for LC-MS studies was established by
      matching the theoretical mass values of the drugs with those obtained
      experimentally. These methods were used to determine mass values of the major
      interaction/degradation products, which helped to know the source of their
      origin.

PMID- 18343074
TI  - Evaluation of restriction enzymes for standardizing pulsed-field gel
      electrophoresis protocol for rapid subtyping of Vibrio parahaemolyticus.
AB  - We evaluated the cost-effectiveness of the restriction enzymes with rare-cutting
      sites in the genome of Vibrio parahaemolyticus RIMD 2210633 for pulsed-field gel
      electrophoresis (PFGE) analysis. The evaluation indicated that PFGE with both
      NotI and SfiI was discriminatory, but NotI was more cost-effective. Based on the
      results of this study, we suggest using NotI and SfiI as the 1st and the 2nd
      restriction enzyme for standardizing the PulseNet PFGE protocol for molecular
      subtyping and global surveillance of V. parahaemolyticus.

PMID- 18343075
TI  - The evaluation of cardiac complaints in marathon runners.
AB  - In the United States there are now approximately 521 marathons, and in 2005
      approximately 432,000 participants completed one. The number of frequent runners
      (more than 100 days a year) is estimated at over 11 million. When one of these
      patients presents to the emergency department with cardiac complaints, the risk
      profile and evaluation may be different than in sedentary subjects. The first and
      most important step to patient evaluation is the history. An electrocardiogram
      (ECG) should be obtained in all patients with suspected cardiac complaints.
      Depending on the study and what is defined as abnormal, 40-80% of athletes' ECGs
      will show some abnormality. A normal ECG has a 96% negative predictive value for
      ruling out structural cardiovascular abnormalities, but a positive predictive
      value for disease of only 7%. The electrocardiogram, cardiac enzymes, and stress
      testing are useful, but should be interpreted in the context of the sport and the
      athlete. Echocardiography and cardiac magnetic resonance imaging are indicated
      for the diagnosis of certain conditions. Cardiology consultation or inpatient
      evaluation may be indicated when a specific disease process is suspected based on
      history, physical examination, or ECG. Some patients may require follow-up for
      further diagnostic testing.

PMID- 18343076
TI  - A child with incomplete Kluver-Bucy syndrome developed during acute encephalitis.

PMID- 18343077
TI  - Outcomes of high pretest probability patients undergoing d-dimer testing for
      pulmonary embolism: a pilot study.
AB  - ELISA (enzyme-linked immunosorbent assay) D-dimer testing is commonly used in the
      evaluation of possible pulmonary embolism (PE) in the emergency department, but
      is not recommended in high pretest probability patients. Whether a negative ELISA
      D-dimer can safely rule out PE in these patients is not known, as there have been
      no large studies comparing ELISA D-dimer results and outcomes in high pretest
      probability patients. This was a prospective observational pilot study of
      emergency department patients evaluated for PE. Patients evaluated for PE had
      pretest probability assessed by the Wells PE Score. High pretest probability was
      defined as: dichotomized Wells Score>4 points and patients with trichotomized
      Wells Score>6 points. Patients had an ELISA D-dimer ordered by the treating
      physician. Pulmonary embolism was defined as: positive computed tomography scan,
      high probability ventilation/perfusion scan, positive pulmonary angiogram, or PE
      on 3-month follow-up. We calculated sensitivity, specificity, positive and
      negative predictive value, and likelihood ratios for the ELISA D-dimer. We
      prospectively enrolled 541 patients who underwent D-dimer testing for PE, of whom
      130 patients had Wells Score>4 and 33 patients had Wells Score>6 (not mutually
      exclusive). Of subjects with Wells Score>4, 23 (18%) were diagnosed with PE and
      40 (31%) had a negative D-dimer. No patient with Wells Score>4 (sensitivity 100%,
      95% confidence interval [CI] 82%-100%; specificity 37%, 95% CI 28%-47%) or Wells
      Score>6 (sensitivity 100%, 95% CI 63%-100%; specificity 56%, 95% CI 35%-76%) who
      had a negative D-dimer was diagnosed with PE. The likelihood ratio for a negative
      D-dimer was 0 for both the Wells>4, and Wells>6 groups, however, the upper limits
      of the confidence interval around the post-test probability for PE were 16% and
      33%, respectively, for these high probability groups. In this pilot study, the
      rapid ELISA D-dimer had high sensitivity and negative predictive value even when
      applied to patients with high pretest probability for PE. However, with the post
      test probability of PE still as high as 16-33% in the negative D-dimer groups,
      this precludes applying the results to patient care at present. Further testing
      is warranted to determine whether these findings can be safely incorporated into
      practice.

PMID- 18343078
TI  - Utility of radiography in suspected ventricular shunt malfunction.
AB  - It is common to evaluate pediatric patients with suspected malfunction of
      intraventricular shunts (VS) with cranial computed tomography (CT) as well as
      radiographs. Yet, the clinical yield of these studies is not well defined. We
      conducted a study to determine if radiographs of VS add useful clinical data in
      the evaluation of shunt malfunctions. A retrospective chart review of children
      evaluated in the emergency department for potential VS malfunction was conducted.
      CT scan results were categorized into five distinct categories based on the
      presence of shunt malfunction and comparison to prior studies. Determination of
      the presence of VS malfunction was based upon the discharge diagnosis. There were
      205 patient encounters identified. The mean age was 5.3 years. Forty-four of the
      visits involved children younger than 2 years of age. Forty-eight children (23%
      of total) were taken to surgery for shunt malfunction. Only 8 had radiography
      demonstrating breakage or discontinuity of the shunt or tubing. Of these, 6 had
      CT scans demonstrating increased intracranial pressure. The remaining 2 had
      vomiting and lethargy, with one also having evidence of cerebrospinal fluid
      extravasation on examination. Overall, CT scans identified 46 of 48 (96%)
      patients with malfunction of their VS. The 2 remaining children had radiographs
      demonstrating abnormality of their VS. Both children, however, had a classic
      clinical presentation of shunt malfunction. In this series, plain radiography in
      patients with suspected shunt malfunction, looking for breakage or discontinuity
      of the shunt, may represent unnecessary ionizing radiation exposure and expense.

PMID- 18343079
TI  - Oral analgesia before pediatric ketamine sedation is not associated with an
      increased risk of emesis and other adverse events.
AB  - The objective of this study was to determine the association between recent
      administration of oral analgesics and frequency of adverse events during ketamine
      sedation in pediatric patients undergoing fracture reduction in the emergency
      department (ED). This retrospective study was conducted in the ED of a large,
      urban pediatric teaching hospital. Subjects were patients aged <or= 18 years seen
      between November 1, 2004 and October 31, 2005 who received ketamine sedation for
      fracture reduction. Patients with and without prior oral analgesia within 6 h of
      ED presentation were compared with respect to emesis and other post-sedation
      complications. Of 471 evaluable patients who underwent ketamine sedation, 201
      received oral analgesia within 6 h. The groups with and without recent oral
      analgesia were similar in age, weight, and fasting duration for solid foods.
      Ketamine doses (in mg/kg) were slightly greater in the no prior oral analgesic
      group (1.40 mg/kg vs. 1.54 mg/kg, respectively, mean difference 0.15 [95%
      confidence interval (CI) -0.26 to -0.03]). Among patients receiving oral
      analgesia, 10 of 201(5%) experienced emesis, in contrast to 7 of 270 (2.6%) in
      the no oral analgesic group, (difference in proportions 2.4% [95% CI -1.1 to
      6.5]). Total adverse events were comparable for groups receiving oral analgesia
      (5%) or no oral analgesia (5.6%, difference in proportions -0.6% [95% CI -4.7% to
      3.9%]). No association was found between administration of oral analgesia before
      procedural sedation and anesthesia and the frequency of emesis or other adverse
      events.

PMID- 18343080
TI  - Metformin overdose with a resultant serum pH of 6.59: survival without sequalae.
AB  - Metformin, widely used in the treatment of diabetes mellitus, is known to cause
      lactic acidosis in both therapeutic use and after an overdose. We report the case
      of a 40-year-old woman who claimed to have ingested between 75 and 100 grams of
      metformin and subsequently developed severe lactic acidosis. She eventually
      developed a peak serum lactate level of 40.0 mmol/L and a serum pH nadir of 6.59
      and became obtunded, hypotensive, and hypothermic. After aggressive supportive
      therapy with mechanical ventilation, vasopressor agents, sodium bicarbonate, and
      hemodialysis, her metabolic derangements steadily improved and she made a
      complete recovery without any residual sequelae. Her admission serum metformin
      concentration was later determined to be 160 microg/mL (therapeutic range is 1-2
      microg/mL). There are several case reports and case series describing lactic
      acidosis secondary to metformin ingestion, although the exact mechanism remains
      unclear. The overall management of metformin overdose is reviewed. This case
      represents the largest reported amount of ingested metformin, the lowest serum
      pH, and the highest serum lactate concentration in any intentional metformin
      overdose survivor in the literature. Despite potentially lethal metabolic
      derangements, such patients can survive with aggressive supportive care.

PMID- 18343081
TI  - Melatonin inhibitory effect on cAMP accumulation in the chick retina development.
AB  - During vertebrate neurodevelopment, neuritogenesis and synaptogenesis are
      modulated by intracellular cAMP rises. Melatonin, which is implicated in neuronal
      differentiation, mainly inhibits this pathway. Here, an investigation about the
      profile of this effect during the vertebrate neurodevelopment is reported. In the
      embryonic chick retinas at days 8, 12, 14, 16 and at 2 days post-hatched (E8,
      E12, E14, E16 and PH), those control embryonic retinas incubated only with the
      phosphodiesterase inhibitor at days corresponding to commencement of neuronal
      differentiation (E8, E12) and PH, presented cAMP levels inhibited by melatonin.
      While the cAMP accumulation stimulated by forskolin was inhibited in the
      embryonic retinas at all testing days. Neither the unselective antagonist N
      acetyl-2-benziltryptamine (luzindole) nor the selective Mel(1b) antagonist 4
      phenyl-2-propionamidotetralin (4-P-PDOT) blocked the melatonin concentration
      dependent inhibitory effect on cAMP accumulation in the retinas initiating
      differentiation (E7-E9), suggesting a tight binding between melatonin and their
      receptors. However, 4-P-PDOT competitively reverted the melatonin effect on cAMP
      stimulated by forskolin during synaptogenesis stages. Together, the melatonin
      effect on cAMP levels in chick retina, which is mainly through melatonin
      receptors, is depending on the developmental period observed, probably taking
      part in the mechanisms surrounding the melatonin action on neuronal
      differentiation.

PMID- 18343082
TI  - An audit of outcomes of a series of periampullary carcinomas.
AB  - BACKGROUND: Non-pancreatic periampullary carcinoma such as ampullary carcinoma
      (AmpCA), distal cholangiocellular carcinoma (CholCA) and duodenal carcinoma
      (DuoCA) have a better prognosis than pancreatic head adenocarcinoma (PanCA). This
      study describes the outcome and parameters, which predict survival of non
      pancreatic periampullary carcinoma after resection. METHODS AND PATIENTS: Data
      from 148 consecutive patients with non-pancreatic periampullary carcinomas were
      recorded prospectively between 1993 and 2005 and analyzed using univariate and
      multivariate models. RESULTS: One hundred thirty-three of 148 (90%) patients were
      resected for histologically proven non-pancreatic periampullary carcinomas. R0
      resection was achieved for 92% of AmpCA, for 88% of CholCA and for all the DuoCA.
      The lowest recurrence rate was seen in DuoCA with 18%, followed by AmpCA with 21%
      and CholCA with 46%. The mean survival time was 60.9 months for AmpCA patients,
      42.9 months for CholCA and 45.4 months for DuoCA patients. Five-year survival was
      50.5%, 29.9% and 24.5% for AmpCA, CholCA and DuoCA, respectively. Multivariate
      analysis identified low bilirubin levels (<100 micromol/l), R0 resections and
      absence of surgical complications to be strong independent predictors of survival
      (p<0.05). In AmpCA low tumor stages are also an independent predictor of long
      term survival (p<0.01). For T1/T2 AmpCA the 5-year survival rate was 61%, whereas
      none of the patients with a T3/T4 tumor survived 5 years. CONCLUSION: Only T1/T2
      ampullary carcinomas have a good prognosis, whereas T3/T4 ampullary tumors show
      aggressiveness similar to that of pancreatic head adenocarcinomas. Absence of
      surgical complications determines long-term outcome. Therefore, the combination
      of a complication-free and radical resection is essential for long-term survival.

PMID- 18343083
TI  - Breast cancer during pregnancy: a mini-review.
AB  - BACKGROUND: As modern women delay childbearing, pregnancy-associated breast
      cancer (PABC) becomes a more frequent problem faced by oncologists,
      gynecologists, and obstetricians alike. However, no evidence exists concerning
      the management of this condition. METHODS: We summarized the current literature
      regarding epidemiology, pathology, diagnosis, treatment and prognosis of PABC.
      Data were collected by searching PubMed and Medline for the period from 1950 to
      2007. RESULTS: There are no randomized controlled trials regarding PABC
      management. Current evidence suggests that diagnosis may be carried out with
      limitations regarding staging; surgical treatment may be performed as for the non
      pregnant women. Radiotherapy and endocrine therapy are contraindicated during
      pregnancy, while chemotherapy is allowed after the first trimester. Prognosis is
      considered poor. Subsequent pregnancy is allowed only 2 years after completing
      treatment. CONCLUSIONS: Due to lack of prospective randomized controlled clinical
      studies, both ongoing studies and future evidence are expected to solve problems
      related to breast cancer management during pregnancy.

PMID- 18343084
TI  - Preoperative predictors of vascular invasion in hepatocellular carcinoma.
AB  - AIMS: Vascular invasion is an established adverse prognostic factor in
      hepatocellular carcinoma (HCC). The aim of the current study was to identify the
      preoperative predictors of vascular invasion in patients undergoing partial
      hepatectomy for HCC. METHODS: A retrospective analysis of 227 consecutive
      patients who underwent partial hepatectomy for HCC was conducted. Vascular
      invasion was defined as gross or microscopic involvement of the vessels (portal
      vein or hepatic vein) within the peritumoral liver tissue. RESULTS: Seventy-six
      (33%) patients had vascular invasion. Among the preoperative factors, only the
      tumour size (relative risk, 16.78; p<0.01) and the serum alpha-fetoprotein (AFP)
      level (relative risk, 3.57; p<0.01) independently predicted vascular invasion. As
      the tumour size increased, the incidence of vascular invasion increased: < or =2
      cm, 3%; 2.1-3 cm, 20%; 3.1-5 cm, 38%; and > 5 cm, 65%. The incidence of vascular
      invasion was 32% in patients with serum AFP levels < or =1000 ng/mL, compared to
      61% in patients with higher serum AFP levels (p<0.01). Patients with both tumours
      >5 cm and serum AFP levels >1000 ng/mL had an 82% incidence of vascular invasion.
      CONCLUSIONS: The tumour size and serum AFP level, alone or in combination, are
      useful in predicting the presence or absence of vascular invasion before
      hepatectomy for HCC.

PMID- 18343085
TI  - [Surgical management of rupture of a subcapsular hepatic haematoma at 39 weeks'
      gestation].

PMID- 18343086
TI  - Antimycobacterial activity of novel N-(substituted)-2
      isonicotinoylhydrazinocarbothioamide endowed with high activity towards isoniazid
      resistant tuberculosis.
AB  - Various isonicotinoylhydrazinocarbothioamides were prepared by reacting
      isonicotinoyl hydrazide (INH) with appropriate potassium salt of substituted
      phenyl thiocarbamate and were tested for their antimycobacterial activity in
      vitro against Mycobacterium tuberculosis H(37)R(v) and INH resistant M.
      tuberculosis using the agar dilution method. Among the synthesized compounds, 2
      isonicotinoyl-N-[2-(trifluoromethyl)phenyl]hydrazinecarbothioamide (4i) was found
      to be the most potent compound with minimum inhibitory concentration of 0.58
      microM against M. tuberculosis H(37)R(v) and INH resistant M. tuberculosis. When
      compared to INH, 4i was found to be 1.24 and 157 times more active against M.
      tuberculosis H(37)R(v) and INH resistant M. tuberculosis respectively, with a
      selectivity index of >218.

PMID- 18343087
TI  - Malingering detection in a Spanish population with a known-groups design.
AB  - Malingering detection has become a topic of increased interest in the US over the
      last years. However, this development has not been matched in Europe. For
      example, in Spain there is insufficient evidence to support the use of reliable
      and valid malingering tests. In this study, we tested the applicability of two
      malingering detection tests (Test of Memory Malingering (TOMM) and Dot Counting
      Test) in a Spanish sample. The sample included three groups of patients (30 non
      compensation seeking, 14 compensation seeking non-suspected of malingering, and
      10 suspected of malingering) and a group of analog students (n=54). Tests'
      results were able to discriminate between the groups of malingerers (both
      patients and analogs) and non-malingerers (both compensation seeking and non
      compensation seeking). However, the TOMM achieved a higher overall classification
      rate than the Dot Counting Test. Our results encourage the use of the TOMM as an
      indicator of malingering with Spanish population.

PMID- 18343088
TI  - Screening for neuropsychological impairment in children using Reitan and
      Wolfson's preliminary neuropsychological test battery.
AB  - This study examined the efficacy of two screening batteries developed by Reitan
      and Wolfson [Reitan, R. M., & Wolfson, D. (2006). Issues in neuropsychology:
      Where have we succeeded? Where have we failed? What are the clinical and forensic
      implications? Presented at the 26th annual conference of the National Academy of
      Neuropsychology] for predicting neuropsychological impairment on the Halstead
      Reitan Neuropsychological Test Battery for Older Children (ages 9-14) and the
      Reitan-Indiana Neuropsychological Test Battery (ages 5-8). Sixty-eight subjects
      were selected from archival data collected from cases in a private practice
      setting. Using Reitan and Wolfson's recommended screening battery
      neuropsychological deficit scale score (SBNDS) cut-off of 16/17 correctly
      classified 82.5% of older children as normal or impaired according to total GNDS
      scores. The screening battery for young children (n=28) resulted in 100% correct
      classification using Reitan and Wolfson's recommended SBNDS cut-off of 22/23.

PMID- 18343089
TI  - Social performance deficits in social anxiety disorder: reality during
      conversation and biased perception during speech.
AB  - Cognitive models emphasize that patients with social anxiety disorder (SAD) are
      mainly characterized by biased perception of their social performance. In
      addition, there is a growing body of evidence showing that SAD patients suffer
      from actual deficits in social interaction. To unravel what characterizes SAD
      patients the most, underestimation of social performance (defined as the
      discrepancy between self-perceived and observer-perceived social performance), or
      actual (observer-perceived) social performance, 48 patients with SAD and 27
      normal control participants were observed during a speech and conversation.
      Consistent with the cognitive model of SAD, patients with SAD underestimated
      their social performance relative to control participants during the two
      interactions, but primarily during the speech. Actual social performance deficits
      were clearly apparent in the conversation but not in the speech. In conclusion,
      interactions that pull for more interpersonal skills, like a conversation, elicit
      more actual social performance deficits whereas, situations with a performance
      character, like a speech, bring about more cognitive distortions in patients with
      SAD.

PMID- 18343090
TI  - Transcriptional and epigenetic status of protamine 1 and 2 genes following round
      spermatids injection into mouse oocytes.
AB  - The use of round spermatids that are fully active at the transcriptional level to
      create zygotes (i.e. round spermatid injection; ROSI) raises the question
      regarding the downregulation of all specific genes that are transcribed from the
      paternal genome at fertilization. In this study, we show that protamine 1 and 2
      mRNAs, which are specific to the round spermatid stage, are repressed at the two
      pronuclei (6 h) and two-cell (30 h) stages postfertilization, respectively, in
      ROSI embryos, by distinct mechanisms. Both genes are fully methylated in round
      spermatids and sperm but unmethylated in oocytes. At 6 h postfertilization, the
      protamine 1 and 2 genes are actively demethylated, but the demethylation process
      happens more rapidly in ROSI than in sperm zygotes. Treatment of zygotes with
      trichostatin A, a histone deacetylase (HDAC) inhibitor, maintained the protamine
      2 mRNAs expression up to 30 h postfertilization while the DNA methylation status
      of the gene is not affected. Thus, HDACs are involved in the clearance of
      protamine 2 mRNAs in ROSI two-cell embryos independently of the methylation
      status of the repressed gene. Contrastingly, HDACs are not directly involved in
      protamine 1 regulation since trichostatin A does not reverse the silencing of the
      gene in ROSI embryos at 6 h. The protamine 1 CpG island located in the coding
      region is actively demethylated in ROSI one-cell embryos where the gene is
      repressed and may contribute to the regulation of protamine 1 gene expression.
      The comparison with gene reprogramming occurring during nuclear transfer makes
      ROSI embryos an attractive model to study the mechanisms involved in gene
      silencing elicited by the oocyte.

PMID- 18343091
TI  - A deletion mutation in Slc12a6 is associated with neuromuscular disease in gaxp
      mice.
AB  - Giant axonopathy (gaxp), an autosomal recessive mouse mutation, exhibits ataxia
      of the hind legs with a slight side-to-side wobble while walking. Within the
      genomic region of the gaxp locus, a total of 94 transcripts were identified; the
      annotation of these genes using OMIM and PubMed yielded three potential candidate
      genes. By cDNA microarray analysis, 54 genes located on or near the gaxp locus
      were found to exhibit differential expression between gaxp and littermate
      controls. Based on microarray data and the known function of genes identified,
      Slc12a6 was selected as the primary candidate gene and analyzed using the Reveal
      technology of SpectruMedix. A 17-base deletion was detected from within exon 4 of
      Slc12a6. Reverse transcriptase polymerase chain reaction validated the difference
      in Slc12a6 expression in different types of mice at the mRNA level, revealing a
      marked reduction in gaxp mice. Western blot analysis indicated that the protein
      product of Slc12a6, the K(+)-Cl(-) cotransporter Kcc3, was not detectable in gaxp
      mice. The causative role of the exon 4 mutation within Slc12a6 in the gaxp
      phenotype was further confirmed by screening multiple inbred strains and by
      excluding the mutation of nearby genes within the gaxp locus.

PMID- 18343092
TI  - Improved detection and annotation of transposable elements in sequenced genomes
      using multiple reference sequence sets.
AB  - Transposable elements (TEs) are ubiquitous components of eukaryotic genomes that
      impact many aspects of genome function. TE detection in genomic sequences is
      typically performed using similarity searches against a set of reference
      sequences built from previously identified TEs. Here, we demonstrate that this
      process can be improved by designing reference sets that incorporate key aspects
      of the structure and evolution of TEs and by combining these sets with Repbase
      Update (RU), which is composed mainly of consensus sequences. Using the
      Arabidopsis genome as a test case, our approach leads to the detection of an
      extra 12.4% of TE sequences. These correspond to novel TE fragments as well as to
      the extension of TE fragments already detected by RU. Significantly, we find that
      TE detection could be readily optimized using only two reference sets, one
      containing true consensus sequences and the other mosaic sequences that capture
      the structural diversity of TE copies within a family.

PMID- 18343093
TI  - DHPC: a new tool to express genome structural features.
AB  - The DHPC (DNA Hilbert-Peano curve) is a new tool for visualizing large-scale
      genome sequences by mapping sequences into a two-dimensional square. It utilizes
      the space-filling function of Hilbert-Peano mapping. By applying a Gauss
      smoothing technique and a user-defined color function, a large-scale genome
      sequence can be mapped into a two-dimensional color image. In the calculated
      DHPCs, many genome characteristics are revealed. In this article we introduce the
      method and show how DHPCs may be used to identify regions of different base
      composition. The power of the method is demonstrated by presenting multiple
      examples such as repeating sequences, degree of base bias, regions of homogeneity
      and their boundaries, and mark of annotated segments. We also present several
      genome curves generated by DHPC to demonstrate how DHPC can be used to find
      previously unidentified sequence features in these genomes.

PMID- 18343094
TI  - Bridging human and animal research: a comparative approach to studies of
      personality and health.
AB  - This article evaluates a comparative approach to personality and health research.
      We (1) review evidence showing that personality exists and can be measured in
      animals, (2) illustrate the benefits of animal studies for human personality
      research, (3) illustrate the benefits of human studies for animal personality
      research, and (4) provide guidelines for making cross-species comparisons. We
      conclude that a comparative approach can provide unique insights into personality
      psychology, especially into research on personality, immunity, and health.

PMID- 18343095
TI  - Effect of bone sialoprotein and collagen coating on cell attachment to TICER and
      pure titanium implant surfaces.
AB  - To improve integration between implants and biological tissues, this study
      compared bone sialoprotein (BSP) as a surface-coating material against the major
      organic and inorganic components of bone, collagen type I and hydroxyapatite
      (TICER). The expression of osteocalcin, osteonectin and transforming growth
      factor ss was evaluated using immunohistochemical staining procedures. The
      distribution patterns of osteoblasts on the surface of pure titanium with a
      smooth machined surface and a rough surface (TICER) were determined by image
      processing using confocal laser scanning microscopy. The results compared to
      uncoated control materials showed that, at all times investigated, the number of
      cells on the surface of the TICER and pure titanium samples differed
      significantly (P<0.1), demonstrating the superiority of TICER over pure titanium
      in this respect. For pure titanium implants, collagen-precoated surfaces were not
      beneficial for the attachment of bone-derived cells with the exception of day 3
      in vitro (P<0.01). BSP-precoated implant surfaces displayed non-significantly
      higher numbers of settled cells. BSP-precoated implant surfaces were beneficial
      for osteoinduction as revealed by osteocalcin and osteonectin expression. BSP
      precoating of the rough TICER implant surface enhanced the osteoinductive effect
      much more than did collagen precoating. These results contribute to the
      consideration of at least two distinct pathways of osseointegration.

PMID- 18343096
TI  - Prognostic factors for adult sarcomas of head and neck.
AB  - The optimal management of adult soft-tissue sarcomas is not clearly established.
      To assess prognostic factors and survival, the experience of 45 recent successive
      cases was reviewed. Data were collected from a retrospective database (1993-2005)
      and statistically analyzed. Rhabdomyosarcomas were excluded. The mean age was
      50.1 years; there were 24 men and 21 women. The main histological subtypes were
      undifferentiated sarcoma (14) and angiosarcoma (10); 21 tumours were grade 3
      (46%). The most frequent primary sites were neck muscles (15, 33%) and scalp (11,
      24%). At presentation, 5 (20%) cases with lymph-node involvement and another 11
      cases (24%) with distant metastasis were observed. The treatment was with
      curative intent in 33 cases (73%). This entailed surgery, with adjuvant
      radiotherapy in 15 cases and adjuvant chemotherapy in 5 cases. The 5-year overall
      survival was 52% (+/-8%). In univariate analysis, the poor prognostic factors
      were high grade, initial metastasis or lymph nodes, absence of surgery, and
      number of surgical procedures. In multivariate analysis, two factors remained
      significant: grade (P=0.006) and absence of surgery (P=0.005). After taking into
      account grade and metastasis at presentation, quality of surgery has prognostic
      value. The primary aim of a multidisciplinary approach to these tumours must
      favour complete resection.

PMID- 18343097
TI  - Preparation and properties of inhalable nanocomposite particles: effects of the
      size, weight ratio of the primary nanoparticles in nanocomposite particles and
      temperature at a spray-dryer inlet upon properties of nanocomposite particles.
AB  - Nanoparticles are expected to be applicable to inhalation as carrier but there
      exist disadvantages because of their size. Their deposition dose to the lung will
      be small. To overcome this problem and utilize nanoparticles for inhalation, we
      have prepared nanocomposite particles as drug carriers targeting lungs. The
      nanocomposite particles are prepared as drug-loaded nanoparticles-additive
      complex to reach deep in the lungs and to be decomposed into nanoparticles when
      they deposit into lung. In this study, we examined the effect of preparation
      condition--inlet temperature, size of primary nanoparticles and weight ratio of
      primary nanoparticles--on the property of nanocomposite particles. When the size
      of primary nanoparticles was 400 nm and inlet temperature was 90 degrees C, only
      the nanocomposite particles containing between 45 and 55% of primary
      nanoparticles could be decomposed into nanoparticles in water. On the other hand,
      when the inlet temperature was 80 degrees C, nanocomposite particles were
      decomposed into nanoparticles independent of the weight ratio of primary
      nanoparticles. Also, the aerodynamic diameter of the nanocomposite particles was
      between 1.5 and 2.5 microm, independent of the weight ratio of primary
      nanoparticles. When the size of primary nanoparticles was 200 nm and inlet
      temperature was 70 degrees C, nanocomposite particles were decomposed into
      nanoparticles independent of the weight ratio of primary nanoparticles. Also, the
      aerodynamic diameters of them were almost 2.0 microm independent of the weight
      ratio of primary nanoparticles. When the nanocomposite particles containing
      nanoparticles with the size of 200 nm are prepared at 80 degrees C, no
      decomposition into nanoparticles was observed in water. Fine particle values,
      FPF, of the nanocomposite particles were not affected by the weight ratio of
      primary nanoparticles when they were prepared at optimum inlet temperature.

PMID- 18343098
TI  - In vitro methods can forecast the effects of intragastric residence on dosage
      form performance.
AB  - Intragastric conditions can affect the performance of solid dosage forms. For two
      cases, the ability of in vitro methods to forecast these effects was
      investigated: first, the ability of cholestyramine to sequester bile salts in the
      fed small intestine and, second, disintegration times of hard gelatin capsules.
      After incubating cholestyramine for 90 min in milk gradually digested with
      pepsin, the binding of taurocholates from fed state simulating intestinal fluid
      onto the resin became non-specific and the affinity constant was reduced from 220
      l/mole (without prior incubation) to 60 l/mole. These data are consistent with
      the comparatively poor performance of cholestyramine products when administered
      in the fed state. Scintigraphic studies showed that intragastric disintegration
      times of hard gelatin capsules are delayed in both the fasted and fed states
      according to the degree of cross-linking. These results were satisfactorily
      predicted by the in vitro disintegration times in fasted state simulating gastric
      fluid and in milk gradually digested with pepsin, whereas results were poorly
      predicted in compendial media. This work illustrates that recently proposed
      methods for simulating intragastric environment may be useful in predicting the
      performance of solid dosage forms.

PMID- 18343099
TI  - Maternal and fetal brain contents of docosahexaenoic acid (DHA) and arachidonic
      acid (AA) at various essential fatty acid (EFA), DHA and AA dietary intakes
      during pregnancy in mice.
AB  - We investigated essential fatty acids (EFA) and long-chain polyunsaturated fatty
      acids (LCP) in maternal and fetal brain as a function of EFA/LCP availability to
      the feto-maternal unit in mice. Diets varying in parent EFA, arachidonic acid
      (AA), and docosahexaenoic acid (DHA) were administered from day 3 prior to
      conception till day 15 of pregnancy. We concentrated on DHA, AA, Mead acid, and
      EFA-index [(omega-3+omega-6)/(omega-7+omega-9)] in maternal erythrocytes,
      maternal brain, and fetal brain. It was found that erythrocyte EFA/LCP
      sensitively reflects declining EFA/LCP status in pregnancy, although this decline
      was not apparent in maternal brain. Differences in erythrocyte EFA/LCP coincided
      with larger differences in fetal brain EFA/LCP as compared to EFA/LCP in maternal
      brain. Both maternal and fetal brains were affected by short-term EFA/LCP intake,
      but the developing fetal brain proved most sensitive. The inverse relationship
      between fetal brain AA and DHA suggests the need of a maternal dietary DHA/AA
      balance, at least in mice.

PMID- 18343100
TI  - Enhanced efficiency of a capillary-based biosensor over an optical fiber
      biosensor for detecting calpastatin.
AB  - A capillary-based optical biosensor has been developed to detect calpastatin, an
      indicator of meat tenderness. Longissimus muscle samples (n=11) were extracted
      from beef carcasses at 0 and 48h post-mortem. These samples were assayed for
      calpastatin by traditional laboratory methods and with a newly developed
      capillary tube biosensor as well as for Warner-Bratzler shear force (WBSF) and
      crude protein and the responses were compared. Additionally, the response from
      the capillary-based biosensor was compared to a previously developed optical
      fiber biosensor. When the 0 and 48h sampling periods were combined, the capillary
      tube biosensor was moderately accurate in predicting calpastatin activity
      (R(2)=0.6058). There was less variation in the 0h capillary tube biosensor
      compared to the 0h pre-column (P=0.006) and post-column optical fiber biosensors
      (P=0.047), therefore the capillary tube biosensor is a more precise system of
      measurement. This research further advances the development of a calpastatin
      biosensor and makes online assessment one step closer to reality.

PMID- 18343101
TI  - Bond-rupture immunosensors--a review.
AB  - It has long been the goal of researchers to develop fast and reliable point-of
      care alternatives to existing lab-based tests. A viable point-of-care biosensor
      is fast, reliable, simple, cost-effective, and detects low concentrations of the
      target analyte. The target of biosensors is biological such as bacteria or virus
      and as such, the antibody-antigen bond derived from the real immune response is
      used. Biosensor applications include lab-based tests for the purposes of
      diagnostics, drug discovery, and research. Additional applications include
      environmental, food, and agricultural monitoring. The main merits of the bond
      rupture method are quick, simple, and capable of discriminating between specific
      and non-specific interactions. The separation of specific and non-specific bonds
      is important for working in real-life complex serums such as blood. The bond
      rupture technique can provide both qualitative results, the detection of a
      target, and quantitative results, the concentration of target. Bond-rupture
      achieves this by a label-free method requiring no pre-processing of the analyte.
      A piezoelectric transducer such as the quartz crystal microbalance (QCM) shakes
      the bound particles free from the surface. Other transducers such as Surface
      Acoustic Wave (SAW) are also considered. The rupture of the bonds is detected as
      electronic noise. This review article links diverse research areas to build a
      picture of a field still in development.

PMID- 18343102
TI  - DNA repair deficiency as a therapeutic target in cancer.
AB  - Inhibitors of DNA repair proteins have been used in cancer therapy, mostly to
      potentiate the effects of cytotoxic agents. However, tumor cells frequently
      exhibit deficiencies in the signalling or repair of DNA damage. These
      deficiencies probably contribute to pathogenesis of the disease, but they also
      present an opportunity to target the tumor. Recently, inhibitors of poly(ADP
      ribose) polymerase (PARP) have been shown to be highly selective for tumor cells
      with defects in the repair of double-strand DNA breaks (DSBs) by homologous
      recombination, particularly in the context of BRCA1 or BRCA2 mutation. It seems
      likely that other DNA repair processes can be targeted in a similar manner. These
      synthetic lethal approaches highlight how an understanding of DNA repair
      processes can be used in the development of novel cancer treatments.

PMID- 18343103
TI  - Cholesterol sulphate sulphohydrolase of human placenta lysosomal membrane.
AB  - In this paper we report that the activity of cholesterol sulphate sulphohydrolase
      (CHS-ase) is associated with the lysosomal membranes. The procedure of
      purification of CHS-ase from human placenta lysosomes was elaborated. The
      purified enzyme is highly specific to cholesterol sulphate (specific activity
      2126.60+/-940.90 nmol min(-1) mg protein(-1)) and acts optimally at pH 3.4. The
      K(M) value for the hydrolysis of cholesterol sulphate is 3.6+/-0.95 x 10(
      5)mol/l. The isoelectric point (pI) has the value 5.7, molecular weight estimated
      by SDS-PAGE electrophoresis is 38 kDa. The described enzyme may be involved in a
      regulation of cholesterol and cholesterol sulphate levels in the lysosomal
      membrane.

PMID- 18343104
TI  - Optimization of biobleaching of paper pulp in an expanded bed bioreactor with
      immobilized alkali stable xylanase by using response surface methodology.
AB  - Purified alkali stable xylanase from Aspergillus fischeri was immobilized on
      polystyrene beads using diazotization method. An expanded bed bioreactor was
      developed with these immobilized beads to biobleach the paper pulp in continuous
      mode. Response surface methodology was applied to optimize the biobleaching
      conditions. Temperature (degrees C), flow rate of pulp (ml/min) and concentration
      of the pulp (%) were selected as variables in this study. Optimal conditions for
      biobleaching process were reaction temperature 60 degrees C, flow rate of 2
      ml/min and 5% (w/v) of pulp. The kappa number reduced from 66 in the unbleached
      pulp to 20 (reduction of 87%). This system proves to be a better option for the
      conventional chlorine based pulp bleaching.

PMID- 18343105
TI  - Thermophilic anaerobic digestion of source-sorted organic fraction of municipal
      solid waste.
AB  - The influence of different organic fraction of municipal solid wastes during
      anaerobic thermophilic (55 degrees C) treatment of organic matter was studied in
      this work: food waste (FW), organic fraction of municipal solid waste (OFMSW) and
      shredded OFMSW (SH_OFMSW). All digester operated at dry conditions (20% total
      solids content) and were inoculated with 30% (in volume) of mesophilic digested
      sludge. Experimental results showed important different behaviours patterns in
      these wastes related with the organic matter biodegradation and biogas and
      methane production. The FW reactor showed the smallest waste biodegradation
      (32.4% VS removal) with high methane production (0.18 LCH4/gVS); in contrast the
      SH_OFMSW showed higher waste biodegradation (73.7% VS removal) with small methane
      production (0.05 LCH4/g VS). Finally, OFMSW showed the highest VS removal (79.5%)
      and the methane yield reached 0.08 LCH4/g VS. Therefore, the nature of organic
      substrate has an important influence on the biodegradation process and methane
      yield. Pre-treatment of waste is not necessary for OFMSW.

PMID- 18343106
TI  - Beta-lactam congeners of orlistat as inhibitors of fatty acid synthase.
AB  - Beta-lactam derivatives of orlistat were prepared and their inhibitory activities
      toward the thioesterase domain of fatty acid synthase (FAS-TE) were evaluated
      using a recombinant form of the enzyme. While in general these derivatives showed
      lower potency compared to beta-lactones, a reasonably potent, lead compound (-)-9
      (IC(50)=8.6microM) was discovered that suggests that this class of compounds
      should be evaluated further.

PMID- 18343107
TI  - Solid-phase synthesis of oligomers carrying several chromophore units linked by
      phosphodiester backbones.
AB  - A method for the preparation of oligomers by linking chromophore units is
      described. Specifically, the synthesis of chromophore units having a protected
      hydroxyl group and a phosphoramidite function is described, along with a method
      to link several units using solid-phase phosphite-triester protocols.

PMID- 18343108
TI  - Synthesis of barbiturate-based methionine aminopeptidase-1 inhibitors.
AB  - The syntheses of a new class of barbiturate-based inhibitors for human and
      Escherichia Coli methionine aminopeptidase-1 (MetAP-1) are described. Some of the
      synthesized inhibitors show selective inhibition of the human enzyme with high
      potency.

PMID- 18343109
TI  - TIE-2/VEGF-R2 SAR and in vitro activity of C3-acyl dihydroindazolo[5,4
      a]pyrrolo[3,4-c]carbazole analogs.
AB  - Orally bioavailable, dual inhibitors of TIE-2/VEGF-R2 were identified by
      elaborating the C3/N13 SAR around a fused pyrrolodihydroindazolocarbazole
      scaffold. Analogs bearing a C3-thiophencarbonyl group were evaluated in enzymatic
      and cellular biochemical assays; two orally bioavailable analogs were further
      profiled in functional assays and found to inhibit microvessel growth in rat
      aortic explant cultures and inhibit Ang-1-stimulated chemotaxis of HUVECs.

PMID- 18343110
TI  - Sugar Chips immobilized with synthetic sulfated disaccharides of heparin/heparan
      sulfate partial structure.
AB  - Carbohydrate chip technology has a great potential for the high-throughput
      evaluation of carbohydrate-protein interactions. Herein, we report syntheses of
      novel sulfated oligosaccharides possessing heparin and heparan sulfate partial
      disaccharide structures, their immobilization on gold-coated chips to prepare
      array-type Sugar Chips, and evaluation of binding potencies of proteins by
      surface plasmon resonance (SPR) imaging technology. Sulfated oligosaccharides
      were efficiently synthesized from glucosamine and uronic acid moieties.
      Synthesized sulfated oligosaccharides were then easily immobilized on gold-coated
      chips using previously reported methods. The effectiveness of this analytical
      method was confirmed in binding experiments between the chips and heparin binding
      proteins, fibronectin and recombinant human von Willebrand factor A1 domain (rh
      vWf-A1), where specific partial structures of heparin or heparan sulfate
      responsible for binding were identified.

PMID- 18343111
TI  - Novel mitochondrial tRNA Leu(CUN) transition and D4Z4 partial deletion in a
      patient with a facioscapulohumeral phenotype.
AB  - Point mutations in mtDNA-encoded tRNA genes frequently cause isolated myopathies
      but rarely cause the facioscapulohumeral phenotype. We report on a patient
      affected with chronic progressive weakness of facioscapulohumeral/peroneal
      muscles whose muscle biopsy showed a mitochondrial myopathy. mtDNA direct
      sequencing and RFLP analysis revealed a heteroplasmic transition T12313C which
      disrupts a conserved site in the T Psi C stem of the tRNA(Leu(CUN)) gene and
      fulfills the accepted criteria of pathogenicity. A partial deletion of the
      nuclear DNA D4Z4 region with residual repeat sizes of 25 kb was also found in the
      patient and in her mother. This is the first reported case of mitochondrial
      myopathy/facioscapulohumeral muscular dystrophy (FSHD) "double trouble".

PMID- 18343112
TI  - Microarray analysis of mdx mice expressing high levels of utrophin: therapeutic
      implications for dystrophin deficiency.
AB  - Duchenne Muscular Dystrophy (DMD) is a fatal muscle wasting disorder caused by
      dystrophin deficiency. Previous work suggested that increased expression of the
      dystrophin-related protein utrophin in the mdx mouse can reduce the dystrophic
      pathophysiology. Physiological tests showed that the transgenic mouse muscle
      functioned in a way similar to normal muscle. More recently, it has become
      possible to analyse disease pathways using microarrays, a sensitive method to
      evaluate the efficacy of a therapeutic approach. We thus examined the gene
      expression profile of mdx mouse muscle compared to wild-type mouse muscle and
      compared the data with that obtained from the transgenic line overexpressing
      utrophin. The data confirm that the expression of utrophin in the mdx mouse
      muscle results in a global gene expression profile more similar to that seen for
      the wild-type mouse. This study confirms that a strategy to up-regulate utrophin
      is likely to be beneficial in dystrophin deficiency.

PMID- 18343113
TI  - Adenovirus and adeno-associated virus-mediated delivery of human myophosphorylase
      cDNA and LacZ cDNA to muscle in the ovine model of McArdle's disease: expression
      and re-expression of glycogen phosphorylase.
AB  - At present there is no satisfactory treatment for McArdle's disease, deficiency
      of myophosphorylase. Injection of modified adenovirus 5 (AdV5) and adeno
      associated virus 2 (AAV2) vectors containing myophosphorylase expression
      cassettes, into semitendinosus muscle of sheep with McArdle's disease, produced
      expression of functional myophosphorylase and some re-expression of the non
      muscle glycogen phosphorylase isoforms (both liver and brain) in regenerating
      fibres. Expression of both non-muscle isoforms was also seen after control
      injections of AdV5LacZ vectors. There was up to an order of magnitude greater
      expression of phosphorylase after myophosphorylase vector injection than after
      LacZ controls (62% of sections with over 1000 positive muscle fibres, versus 7%).
      The results presented here suggest that the use of viral vector-mediated
      phosphorylase gene transfer may be applicable to the treatment of McArdle's
      disease and that sustained re-expression of the brain and liver isoforms should
      also be investigated as a possible treatment.

PMID- 18343114
TI  - Expression of caveolar components in primary desminopathy.
AB  - Myofibrillar myopathies (MFM) involve accumulation of various proteins in the
      muscle cytoplasm. In myopathy with a heterozygous A337P mutation of the desmin
      gene, electron-micrographs showed aggregates of vesicular and tubular structures.
      Positive cytoplasmic reaction for caveolin-3 immunohistochemistry and cholera
      toxin B binding suggested that caveolae comprised some of the aggregates. As
      caveolae occur in the Golgi complex and are transported to the cell surface, the
      results suggest inhibition of their trafficking to the sarcolemma. Alternatively,
      they could be trapped during internalization. We hypothesize that the
      accumulation of multiple proteins in MFM could be partially due to inhibited
      intracellular trafficking.

PMID- 18343115
TI  - Genotype-phenotype analysis in patients with giant axonal neuropathy.

PMID- 18343116
TI  - Elevation of neuron-specific enolase and S-100beta protein level in experimental
      acute spinal cord injury.
AB  - We evaluated the protein levels of neuron-specific enolase (NSE) and S-100beta in
      serum and cerebrospinal fluid (CSF) in an animal model of acute spinal cord
      injury and ascertained their relevance. Spinal cord injury was induced at the T8
      level in rats. Enzyme-linked immunosorbent assay was used to measure the protein
      levels of NSE and S-100beta in both serum and CSF at different time points (30
      min, 2 h, 6 h, 12 h and 24 h after induction of spinal cord injury). There
      existed a significant correlation between neurological deficits and the severity
      of spinal cord injury (p<0.05). Compared with the control group, the protein
      levels of NSE and S-100beta in serum and CSF significantly increased from 2 h
      after injury (p<0.05) and reached a maximum at 6 h. Within a certain time window,
      the protein levels of NSE and S-100beta in serum and CSF were closely related to
      the severity of injury level (p<0.05). The protein levels of NSE and S-100beta in
      serum and CSF significantly increased after experimental spinal cord injury in a
      time-dependent manner and thus may be considered specific biomarkers for acute
      spinal cord injury.

PMID- 18343117
TI  - Connective tissue disorders in dissections of the carotid or vertebral arteries.
AB  - Dissections of the carotid or vertebral arteries are a significant cause of
      ischemic stroke. Their etiology includes not only mechanical forces but also
      underlying arteriopathies such as Ehlers-Danlos syndrome type IV and other
      connective tissue disorders. Furthermore, dissections often occur spontaneously
      or after minor trauma in otherwise healthy individuals without clinically evident
      underlying aberrations. However, in some of these patients ultrastructural
      connective tissue changes can be detected. An overview of connective tissue
      disorders associated with dissections of the carotid or vertebral arteries is
      presented.

PMID- 18343118
TI  - Tauroursodeoxycholic acid and secondary damage after spinal cord injury in rats.
AB  - Greater clinical understanding of the pivotal role of apoptosis in spinal cord
      injury (SCI) has led to new and innovative apoptosis-based therapies for patients
      with an SCI. Tauroursodeoxycholic acid (TUDCA) is a biliary acid with
      antiapoptotic properties. To our knowledge, this is the first study in the
      English language to evaluate the therapeutic efficacy of TUDCA in an experimental
      model of SCI. Thirty rats were randomized into three groups (sham-operated,
      trauma only, and trauma plus TUDCA treatment) of 10 each. In groups 2 and 3,
      spinal cord trauma was produced at the T8-T10 level via the Allen weight drop
      technique. Rats in group 3 were treated with TUDCA (200 mg/kg intraperitoneal) 1
      min after trauma. The rats were killed either 24 h or 5 days after injury. The
      neuroprotective effect of TUDCA on injured spinal cord tissue and the effects of
      that agent on the recovery of hind-limb function were assessed. The efficacy of
      treatment was evaluated with histopathologic examination and terminal
      deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL)
      analysis. Histopathologic characteristics were analyzed by comparison of
      hematoxylin-and-eosin stained specimens. Neurologic evaluations were performed 24
      h, 3 days, and 5 days after trauma. Hind-limb function was assessed with the
      inclined plane technique of Rivlin and Tator and the modified version of Tarlov's
      grading scale. Twenty-four hours after injury, there was a significantly higher
      number of apoptotic cells in the lesioned spinal cord group than in the sham
      operated control group. Treatment of the rats with TUDCA significantly reduced
      the number of apoptotic cells (4.52+/-0.30 vs. 2.31+/-0.24 in group 2) and the
      degree of tissue injury. Histopathologic examination showed that group 3 rats had
      better spinal cord architecture compared with group 2 rats. Five days after
      injury, the mean inclined plane angles in groups 1, 2, and 3 were 65.50 degrees
      +/- 2.09, 42.00 degrees +/- 2.74, and 53.50 degrees +/- 1.36. Motor grading of
      the rats revealed a similar trend. These differences were statistically
      significant (p<0.05). The mechanism of neuroprotection in the treated rats,
      although not yet elucidated, may be related to the marked antiapoptotic
      properties of TUDCA. A therapeutic strategy using TUDCA may eventually lead to
      effective treatment of SCI without toxic effects in humans.

PMID- 18343119
TI  - Non-steroidal anti-inflammatory drug use and the risk of Parkinson disease: a
      retrospective cohort study.
AB  - Using the British Columbia Linked Health Databases, we explored the association
      between nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of developing
      Parkinson's disease (PD). We followed a cohort of older adults in the Province of
      British Columbia from 1997 to 2003. A time-dependent Cox model was used to
      estimate adjusted rate ratios for users and non-users of NSAIDs. The results of
      our study did not show a protective effect of NSAIDs for PD (rate ratio 0.84, 95%
      CI 0.81-1.09).

PMID- 18343120
TI  - Active core structure of terfestatin A, a new specific inhibitor of auxin
      signaling.
AB  - The auxins, plant hormones, regulate many aspects of the growth and development
      of plants. Terfestatin A (TrfA), a novel auxin signaling inhibitor, was
      identified in a screen of Streptomyces sp. F40 extracts for inhibition of the
      expression of an auxin-inducible gene. However, the mode of action of TrfA has
      not been elucidated. To identify the active core structure, 25 derivatives of
      TrfA were synthesized and their inhibitory activities against auxin-inducible
      gene expression were evaluated. The structure-activity relationships revealed the
      essential active core structure of TrfA, 3-butoxy-4-methylbiphenyl-2,6-diol,
      which will lead to the design of biotin-tagged active TrfA.

PMID- 18343121
TI  - Structure-based virtual screening against SARS-3CL(pro) to identify novel non
      peptidic hits.
AB  - Severe acute respiratory syndrome is a highly infectious upper respiratory tract
      disease caused by SARS-CoV, a previously unidentified human coronavirus. SARS
      3CL(pro) is a viral cysteine protease critical to the pathogen's life cycle and
      hence a therapeutic target of importance. The recently elucidated crystal
      structures of this enzyme provide an opportunity for the discovery of inhibitors
      through rational drug design. In the current study, Gold docking program was
      utilized to conduct extensive docking studies against the target crystal
      structure to develop a robust and predictive docking protocol. The validated
      docking protocol was used to conduct a structure-based virtual screening of the
      Asinex Platinum collection. Biological evaluation of a screened selection of
      compounds was carried out to identify novel inhibitors of the viral protease.

PMID- 18343122
TI  - Inhibitors of DNA polymerase beta: activity and mechanism.
AB  - Bioassay-guided fractionation of extracts prepared from Couepia polyandra and
      Edgeworthia gardneri resulted in the isolation of the DNA polymerase beta (pol
      beta) inhibitors oleanolic acid (1), edgeworin (2), betulinic acid (3), and
      stigmasterol (4). Study of these pol beta inhibitors revealed that three of them
      inhibited both the lyase and polymerase activities of DNA polymerase beta, while
      stigmasterol inhibited only the lyase activity. Further investigation indicated
      that the four inhibitors had substantially different effects on the DNA-pol beta
      binary complex that is believed to be an obligatory intermediate in the lyase
      reaction. It was found that the inhibitors potentiated the inhibitory action of
      the anticancer drug bleomycin in cultured A549 cells, without any influence on
      the expression of pol beta in the cells. The results of the unscheduled DNA
      synthesis assay support the thesis that the potentiation of bleomycin
      cytotoxicity by DNA pol beta inhibitors was a result of an inhibition of DNA
      repair synthesis.

PMID- 18343123
TI  - Natural and non-natural prenylated chalcones: synthesis, cytotoxicity and anti
      oxidative activity.
AB  - A general strategy for the synthesis of 3'-prenylated chalcones was established
      and a series of prenylated hydroxychalcones, including the hop (Humulus lupulus
      L.) secondary metabolites xanthohumol (1), desmethylxanthohumol (2),
      xanthogalenol (3), and 4-methylxanthohumol (4) were synthesized. The influence of
      the A-ring hydroxylation pattern on the cytotoxic activity of the prenylated
      chalcones was investigated in a HeLa cell line and revealed that non-natural
      prenylated chalcones, like 2',3,4',5-tetrahydroxy-6'-methoxy-3'-prenylchalcone
      (9, IC(50) 3.2+/-0.4microM) as well as the phase 1 metabolite of xanthohumol (1),
      3-hydroxyxanthohumol (8, IC(50) 2.5+/-0.5microM), were more active in comparison
      to 1 (IC(50) 9.4+/-1.4microM). A comparison of the cytotoxic activity of
      xanthohumol (1) and 3-hydroxyxanthohumol (8) with the non-prenylated analogs
      helichrysetin (12, IC(50) 5.2+/-0.8) and 3-hydroxyhelichrysetin (13, IC(50)
      14.8+/-2.1) showed that the prenyl side chain at C-3' has an influence on the
      cytotoxicity against HeLa cells only for the dihydroxylated derivative. This
      offers interesting synthetic possibilities for the development of more potent
      compounds. The ORAC activity of the synthesized compounds was also investigated
      and revealed the highest activity for compounds 12, 4'-methylxanthohumol (4), and
      desmethylxanthohumol (2), with 4.4+/-0.6, 3.8+/-0.4, and 3.8+/-0.5 Trolox
      equivalents, respectively.

PMID- 18343124
TI  - Synthesis, penetrability and intracellular targeting of fluorescein-tagged
      peptoids and peptide-peptoid hybrids.
AB  - The search for novel, generally applicable and highly efficient delivery tools is
      a major activity in the biotechnology arena. Using highly optimized microwave
      based solid-phase chemistry a series of fluorescein-labelled cationic peptoid
      conjugates were synthesized within 24h and cellular uptake into HeLa, L929 and
      K562 cells examined via flow cytometry. As expected, analysis revealed that
      longer oligomers achieved greater cellular penetration (7e (9 mer)>7d (7 mer)>7c
      (5 mer)>7b (3 mer)>7a (1 mer)) with the nonamer 7e proving to be a remarkable
      vehicle for all the cell lines, showing excellent penetrability into K562 and
      L929 cells and extraordinary cell delivery into HeLa cells. Confocal microscopy
      showed that the hybrid peptoid-nuclear localizing sequence (PKKKRKV from the
      simian virus 40 large T antigen) resulted in very high levels of nuclei delivery
      after 3h, opening up a range of applications such as nuclei staining of living
      cells with non-DNA-intercalating fluorescent probes.

PMID- 18343125
TI  - Formation of fluorine-18 labeled diaryl ureas--labeled VEGFR-2/PDGFR dual
      inhibitors as molecular imaging agents for angiogenesis.
AB  - Urea subunits are common components of various pharmaceuticals' core structure.
      Since in most cases the design and development of PET biomarkers is based on
      approved or potential drugs, there is a growing need for a general labeling
      methodology of urea-containing pharmacophores. As a part of research in the field
      of molecular imaging of angiogenic processes, we synthesized several highly
      potent VEGFR-2/PDGFR dual inhibitors as potential PET biomarkers. The structure
      of these inhibitors is based on the N-phenyl-N'-{4-(4-quinolyloxy)phenyl}urea
      skeleton. A representative inhibitor was successfully labeled with fluorine-18 by
      a three-step process. Initially, a two-step radiosynthesis of 4-[(18)F]fluoro
      aniline from 1,4-dinitrobenzene (60min, EOB decay corrected yield: 63%) was
      performed. At the third and final step, the 4-[(18)F]fluoro-aniline synthon
      reacted for 30min at room temperature with 4-(2-fluoro-4-isocyanato-phenoxy)-6,7
      dimethoxy-quinoline to give complete conversion of the labeled synthon to 1-[4
      (6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-3-(4-[(18)F]fluoro-phenyl)
      urea. The desired labeled product was obtained after total radiosynthesis time of
      3h including HPLC purification with 46+/-1% EOB decay corrected radiochemical
      yield, 99% radiochemical purity, 99% chemical purity, and a specific activity of
      400+/-37GBq/mmol (n=5).

PMID- 18343126
TI  - Co-existence of alpha-glucosidase-inhibitory and liver X receptor-regulatory
      activities and their separation by structural development.
AB  - Liver X receptors (LXR), which were originally reported as oxysterol-activated
      nuclear receptors, were recently found to recognize glucose as a physiological
      ligand. On this basis, we have already developed novel LXR antagonists based upon
      alpha-glucosidase inhibitors derived from thalidomide. Here, to clarify the
      relationship between alpha-glucosidase inhibition and LXR modulation, we
      investigate the alpha-glucosidase-inhibitory activity of typical LXR ligands and
      the LXR-modulating activity of typical alpha-glucosidase inhibitors. Although
      there were some exceptions, co-existence of LXR-regulatory and alpha-glucosidase
      inhibitory activities seemed to be rather general among the examined compounds.
      The LXR ligands were found to be non-competitive alpha-glucosidase inhibitors,
      suggesting that it might be possible to separate the two activities. To test this
      idea, we focused on riccardin C, a naturally occurring LXR ligand, which we found
      here to be a potent alpha-glucosidase inhibitor as well. Structural development
      of riccardin C afforded novel LXR antagonists lacking alpha-glucosidase
      inhibitory activity, 19c and 19f, and a LXRalpha-selective antagonist, 22.

PMID- 18343127
TI  - Enantiospecific synthesis and cytotoxicity of 7-(4-methoxyphenyl)-6-phenyl
      2,3,8,8a-tetrahydroindolizin-5(1H)-one enantiomers.
AB  - An enantiospecific synthesis was developed to generate both enantiomers of 7-(4
      methoxyphenyl)-6-phenyl-2,3,8,8a-tetrahydroindolizin-5(1H)-one. A biological
      assay utilizing the HCT-116 colon cancer cell line to determine the cytotoxicity
      of these analogs revealed that only the (R)-enantiomer exhibited appreciable
      cytotoxicity with an IC(50) value of 0.2 microM.

PMID- 18343128
TI  - Beta-turn secondary structure and melanocortin ligands.
AB  - The melanocortin pathway has emerged during this past decade as an important
      target area for the discovery and development of therapeutic agents related to
      obesity and type 2 diabetes. This peptide-G-protein coupled receptor (GPCR)
      pathway has evolved from peptide-based ligands to small molecules possessing a
      variety of different molecular scaffolds. Herein, we summarize the originating
      hypothesis of the importance of the reverse beta-turn secondary structure for
      agonist ligand potency at the melanocortin receptors and how that information was
      utilized for the discovery of small molecules based upon this type of turn
      structure.

PMID- 18343129
TI  - A road less traveled by: exploring a decade of Ellman chemistry.
AB  - The Ellman group has been one of the most influential in the development and
      widespread adoption of combinatorial chemistry techniques for biomedical
      research. Their work has included substantial methodological development for
      library synthesis with a particular focus on new scaffolds rationally targeted to
      biomolecules of interest and biologically relevant natural products. Herein we
      analyze a representative set of libraries from this group with respect to their
      biological and biomedical relevance in comparison to existing drugs and probe
      compounds. This analysis reveals that the Ellman group has not only provided new
      methodologies to the community but also provided libraries with unique potential
      for further biological study.

PMID- 18343130
TI  - Half analytical method with application to the high order Laue zone effects in
      monoclinic and triclinic crystals.
AB  - The simulation of the high order Laue zone (HOLZ) diffractions of monoclinic and
      triclinic crystals is a very complicated problem. The conventional multislice
      (MS) method suffers from the problem of infinity of the phase grating size. To
      avoid the difficulty of the infinity, Chen et al. arranged the phase grating
      plane along the ab plane of the crystal lattice. In this paper we introduce a new
      method which allows the incident and exit wavefunction planes perpendicular to
      the zone axis without the difficulty of infinity. We name the method half
      analytical method. The results calculated by half analytical method are in good
      agreement with those calculated by the conventional MS method.

PMID- 18343131
TI  - Morphological and histological effects on the medial pterygoid muscle after
      unilateral exodontia in gerbils.
AB  - Morphological effects on the medial pterygoid muscle were evaluated in 20 male
      gerbils (average weight, 55 g) after occlusal alterations induced by extraction
      of left side molar teeth. Controls were only submitted to surgical stress. Sixty
      days after surgery, the groups were divided into two subgroups for the following
      studies: (1) observation of macroscopic morphology and vessels distribution
      (n=10); (2) light microscopy histological analysis (n=10). Group results were
      statistically compared using the Wilcoxon and Mann-Whitney tests, with a
      significant value of p<0.05. Statistical differences in biometric data were found
      between the left and right sides of the experimental group (p=0.043), and between
      the left side of the control group when compared to the same side in the
      experimental group (p=0.044). Vessels supplied by bundles of the external carotid
      artery in the medial pterygoid muscle did not show distribution differences in
      group comparisons. Histological alterations were found in the ipsilateral side of
      the experimental group, with a central localization of the nucleus and
      degenerative aspect of the fibers, usually near to internal aponeurosis. Fiber
      diameters seemed reduced and the neuromuscular spindles were localized near
      internal aponeurosis and had a modified appearance. It is concluded that the
      medial pterygoid muscle in the gerbil is sensitive to alterations of the
      masticatory movements.

PMID- 18343132
TI  - Analysis of the results of the international comparison of activity measurements
      of a solution of (55)Fe.
AB  - The results of an international comparison of activity measurements of a solution
      of (55)Fe organized by the BIPM in 2005 are reported and analysed. This exercise,
      which follows the procedures of the CIPM mutual recognition arrangement to update
      older comparisons, is a renewal of the comparison organized by the BIPM that took
      place in 1978. A EUROMET comparison was organized in 1996 specifically to compare
      activity measurements of a (55)Fe solution by means of liquid-scintillation
      techniques. Results of these three comparisons are presented and discussed in
      this paper. The radionuclide solution was provided by the NPL, which also
      distributed the samples to the participants. The activity of the ampoules was
      measured by 16 laboratories using 12 methods producing 25 results. Some general
      considerations on uncertainty assessments pertaining to the different techniques
      used are drawn. The outcome of four different estimators is compared from which
      the presence of at least one outlier can be confirmed. Further measurements
      should be made to try to reduce the discrepancy between the results. To date the
      outcome of the present comparison does not show an improvement to that of the
      1996 comparison.

PMID- 18343134
TI  - IAEA Coordinated Research Project: updated decay data library for actinides.
AB  - Recommended nuclear decay data for specific actinides are important in fuel-cycle
      studies for thermal and fast reactors and inventory studies for safeguards.
      Therefore, a programme of work was initiated in 2005 to improve the actinide
      decay data library of the International Atomic Energy Agency through the efforts
      of a Coordinated Research Project (CRP). The proposed contents of the new
      database are described, including the agreement to include additional actinides
      and a significant number of natural decay chain radionuclides. This work is on
      going, and is estimated for completion in 2009/10.

PMID- 18343135
TI  - Determination of radioiodine activity in charcoal cassettes.
AB  - Sampling of radioiodine in air is accomplished by passing an air sample through
      an activated charcoal cassette. A mathematical model was developed, which assumes
      that radioiodine distribution along the cassette axis can be expressed by an
      exponential function. The model was validated experimentally for cassettes used
      for air sampling of radioiodine production boxes. There is a good agreement
      between the measurements and model predictions. Furthermore, when breakthrough
      occurs, the model can be used to estimate the activity that passed through the
      cassette unabsorbed.

PMID- 18343136
TI  - A low-noise current-sensitive amplifier-discriminator system for beta particle
      counting.
AB  - NPL has developed a low-noise current amplifier/discriminator system for
      radionuclides that emit low-energy electrons and X-rays. The new beta amplifier
      is based on the low-noise Amptek A-250 operational amplifier. The design has been
      configured for optimum signal to noise ratio. The new amplifier is described and
      results obtained using primarily electron-capture decaying radionuclides are
      presented. The new amplifier gives rise to higher particle detection efficiency
      than the previously used Atomic Energy of Canada Limited-designed amplifier. This
      is shown by measurements of (54)Mn and (65)Zn. The counting plateaux are
      significantly longer and have reduced gradients.

PMID- 18343137
TI  - Cascades of pile-up and dead time.
AB  - Count loss through a cascade of pile-up and dead time is studied. Time interval
      density-distribution functions and throughput factors are presented for counters
      with a series arrangement of pile-up and extending or non-extending dead time. A
      counter is considered, where an artificial dead time is imposed on every counted
      event, in order to control the length and type of dead time. For such a system,
      it is relatively easy to determine an average count-loss correction factor via a
      live-time clock gated by the imposed dead-time signal ('live-time mode'), or
      otherwise to apply a correction factor based on the inversion of the throughput
      function ('real-time mode'). However, these techniques do not account for
      additional loss through pulse pile-up. In this work, counting errors associated
      with neglecting cascade effects are calculated for measurements in live-time and
      real-time mode.

PMID- 18343138
TI  - Standardisation of (56)Co and (57)Co using software coincidence counting system.
AB  - Activities of the radionuclides (56)Co and (57)Co were determined by the
      efficiency extrapolation method applied to 4pi(PC)-gamma coincidence counting.
      Solutions of (56)Co usually contain a significant amount of (57)Co and (58)Co, so
      the measured activity of (56)Co requires correction. When the conventional
      coincidence method is used for (56)Co standardisation, the corrections are
      derived from the dependence of Proportional Counter (PC) detection efficiencies
      for (57)Co and (56)Co measured using sources with mixture of (56)Co and (57)Co,
      which is complicated. These difficulties were reduced by means of a software
      coincidence method, with a HPGe detector in gamma channel, where the detection
      efficiencies were evaluated directly from the records of coincidence measurements
      of standardised sources. In the case of (57)Co standardisation, the software
      coincidence counting system was applied for the evaluation of optimal setting of
      coincidence parameters. The results obtained by software coincidence counting
      system were compared with those obtained by the conventional coincidence method.

PMID- 18343139
TI  - Investigating the background of a 1-cm(3) quartz gas proportional counter.
AB  - The background count rate of a 1-cm(3) quartz gas proportional counter (GPC) was
      investigated for measuring natural radioactivity levels of small samples. Using a
      new multiparameter digital counting system, spurious or afterpulses that
      contribute to background were identified by their pulse waveform and by a special
      event indicator defined by the time (<2000micros) between two successive pulses.
      With the GPC in coincidence with a low-background NaI(Tl) scintillation guard
      detector, the weighted mean and standard uncertainty anticoincidence counts per
      day (d(-1)) was 6.2+/-0.4d(-1).

PMID- 18343140
TI  - Study of a Monte Carlo rearrangement model for the activity determination of
      electron-capture nuclides by means of liquid scintillation counting.
AB  - A new Monte Carlo approach for the computation of the electron spectra of
      electron-capture nuclides is applied to obtain efficiencies in liquid
      scintillation counting for CIEMAT/NIST applications. The new method is applied to
      the radionuclides (109)Cd and (125)I by using a stochastic atomic rearrangement
      model, taking into account rearrangement processes including L-, M-, and N
      subshells. The counting efficiencies were computed with the new code MICELLE
      which also comprises an approach for calculating the counting efficiency of a
      radionuclide in a gel phase sample. The calculated counting efficiencies are
      compared with experimental results.

PMID- 18343141
TI  - Measurement of (55)Fe solution activity by LSC-TDCR method.
AB  - A solution of (55)Fe was measured by using liquid scintillation counting (LSC)
      TDCR method. The measurement was performed within the frame of the CIPM CCRI(II)
      K2.Fe-55 comparison during the year 2006. Two computation codes were used for the
      calculation of detection efficiency, the difference between the results being
      analyzed. The photomultipliers asymmetry and its influence on the results, as
      well as the long-term stability are also analyzed. The influence of the variation
      of kB value over the activity value is compared with the case of (3)H
      standardization.

PMID- 18343142
TI  - A tool for processing decay scheme data that encompasses coincidence summing
      calculations.
AB  - A description is given of the tool implemented in GESPECOR to process coincidence
      summing corrections and derive decay scheme data. The method of analysis produces
      relevant decay scheme data and the joint emission probability for any group of
      photons (gamma emissions, X-rays, annihilation photons resulting from beta(+)
      decay) emitted in the decay of any nuclide with less than 100 levels.

PMID- 18343143
TI  - Ultra-low-level determination of (236)U in IAEA marine reference materials by
      ICPMS and AMS.
AB  - The development of analytical procedures for the measurement of ultra-low levels
      of (236)U in marine samples using high-resolution inductively coupled plasma mass
      spectrometry (HR-ICPMS) and accelerator mass spectrometry (AMS) techniques are
      discussed and results are presented for IAEA reference materials-marine sediments
      (IAEA-135, 306, 384 and 385), marine biota (IAEA-134 and 414) and seawater (IAEA
      381), collected in areas affected by nuclear reprocessing plants and nuclear
      weapons tests. The obtained minimum detection limit of the (236)U/(238)U atom
      ratio was 1x10(-8) for AMS and 1x10(-6) for HR-ICPMS.

PMID- 18343144
TI  - Experimental determination of the HPGe spectrometer efficiency curve.
AB  - A review of the calibration procedures of the semiconductor HPGe spectrometer is
      presented in this paper. Calibration standards were prepared using the
      standardized radioactive solution of the common monoenergetic radionuclides
      mixture and standardized multigamma (152)Eu solution. The matrix materials were
      spiked using the activated carbon, and homogenized mechanically or by suspension
      in C(2)H(5)OH. Experimentally determined efficiency curves were compared with
      those obtained by Monte Carlo simulation.

PMID- 18343145
TI  - Differential regulation of phenylalanine ammonia lyase activity and protein level
      by light in tomato seedlings.
AB  - Red light, acting via phytochrome, stimulates phenylalanine ammonia lyase (PAL)
      activity in cotyledons and hypocotyls of tomato seedlings. The time course of
      photoinduction of PAL activity has a peak level at 4 h after which activity
      declines significantly. In tomato seedlings PAL activity comprised of three
      isoforms and light stimulated activity of all three isoforms. A polyclonal
      antibody raised against PAL purified from tomato leaves recognized PAL protein
      belonging to PAL-II and PAL-III isoforms. The mode of increase in PAL activity
      was investigated by immunochemical techniques. The photostimulated increase in
      PAL activity appeared to be dependent on de novo synthesis of protein and nucleic
      acid. However, inhibition of protein phosphatase activity blocked increase in PAL
      activity without affecting the increase in PAL protein levels. The results
      indicate that in addition to de novo synthesis, the photostimulation of PAL
      activity likely requires dephosphorylation by a type 2C protein phosphatase.

PMID- 18343146
TI  - Functional role of polyhydroxy compounds on protein structure and thermal
      stability studied by circular dichroism spectroscopy.
AB  - Polyhydroxy compounds such as cyclitols, acyclic polyols and sugars are produced
      by a wide variety of organisms under stressful conditions in order to protect
      macromolecular structure. Plants undergoing abiotic stresses like heat and
      dehydration accumulate enormous amounts of polyhydroxy compounds (up to 400 mM)
      in their cellular tissues. Not only do they serve as osmoprotectants ("compatible
      solutes"), they also protect membrane structure and preserve enzymatic activity.
      To gain further insight into the mechanism of protein protection by polyhydroxy
      compounds, we examined the structural and thermal stability of six model proteins
      (bovine serum albumin, glutamine synthetase of Escherichia coli, malate
      dehydrogenase of pig heart, SH2 domain of phospholipaseCgamma1, SH2_Myc and
      GST_MycMax fusion proteins) upon the addition of various polyhydroxy compounds by
      circular dichroism spectroscopy. Our results show that D-pinitol (1D-3-O-methyl
      chiro-inositol), L-quebrachitol (1L-2-O-methyl-chiro-inositol), myo-inositol, D
      chiro-inositol, mannitol, glucose and trehalose promoted improved structural and
      thermal stability for each protein, whereas conduritol (1,4/2,3
      cyclohexanetetrol) and glycerol were not effective. An increase in the midpoint
      denaturation temperature (T(m)) of 3.3 degrees C to 4.7 degrees C was observed
      for each protein upon the addition of 400 mM myo-inositol. Although the apparent
      T(m) of each protein was shifted by the addition of polyhydroxy compounds, the
      influence seems to be dependent on attributes like the protein surface topology,
      the hydration shell and on the nature of the protective solute, as well as on its
      concentration. The O-methylated cyclitols D-pinitol and L-quebrachitol were more
      effective preservatives than the less hydrophobic non-methylated myo-inositol and
      D-chiro-inositol. Amongst various polyhydroxy compounds, hydrophobic cyclitols
      were the most effective stabilizers.

PMID- 18343147
TI  - Calcified aneurysm of the left ventricle mimicking hydatid disease of the lung.

PMID- 18343148
TI  - Pericardial patch augmentation for repair of incompetent bicuspid aortic valves
      at midterm.
AB  - OBJECTIVE: Reoperation rates after repair of bicuspid aortic valves are higher
      than for mitral valve reconstruction. Satisfactory results have been reported for
      patch augmentation for tricuspid aortic valves. We have applied this technique
      for the repair of bicuspid aortic valves. METHODS: Autologous pericardium is
      sutured to the free edge of the prolapsing bicuspid leaflet. A large coaptation
      surface is created and competence of the bicuspid valve is achieved. Forty
      patients underwent reconstruction of their bicuspid aortic valves by pericardial
      patch augmentation. Patients were followed up at regular intervals by
      echocardiography in yearly intervals. RESULTS: There were no perioperative
      deaths. One year postoperatively, one patient died due to endocarditis. Seven
      patients (17.5%) had aortic regurgitation grade I, and the other 33 patients had
      non or trivial aortic regurgitation at discharge. At 4.2+/-3.1 years
      postoperatively, only four patients (10%) had aortic regurgitation grade I. There
      were no cases of progression of regurgitation. Planimetric effective orifice
      areas ranged above 2 cm2. Mean aortic gradients dropped from 8.2+/-4.8 mmHg at
      discharge to 3.8+/-3 at four years and the mean height of coaptation surface from
      14.7+/-2mm to 12.3+/-4, respectively. CONCLUSIONS: The pericardial patch
      augmentation technique increases coaptation surface, and thus provides reliable
      early and midterm competence of reconstructed bicuspid aortic valves.

PMID- 18343149
TI  - Lung metastasis resection of adenoid cystic carcinoma of salivary glands.
AB  - BACKGROUND: Adenoid cystic carcinoma is a rare tumour originating from the
      exocrine mucous glands, known for its high propensity for distant metastases. The
      value of lung metastasis resection from adenoid cystic carcinoma of salivary
      glands origin is evaluated. METHODS: A retrospective study was conducted on
      patients undergoing surgery for primary adenoid cystic carcinoma of the salivary
      glands between 1982 and 2006. Patients were excluded who had primary tumour
      macroscopic incomplete resection or were lost at follow-up. From a database of 50
      eligible patients, 27 were identified as having presented a tumour recurrence
      during follow-up; in 20 it was first diagnosed in the form of distant metastases,
      and in 7 in the form of loco-regional recurrence. Nine patients who presented
      isolated lung recurrence underwent complete lung metastasectomy. Demographic
      data, pathologic characteristics and operative and postoperative record were
      reviewed, as well as updated survival. RESULTS: Twenty-six men and 24 women with
      a median age of 57 years (range 33-79) underwent radical surgery for adenoid
      cystic carcinoma during the study period. In 20 patients, at a median free
      interval time of 3 years (range 1-12), a distant metastasis relapse was observed.
      Nine patients with a median free interval time of 5 years (range 1-12) underwent
      lung metastasectomy: five had single metastasis resection, one multiple mono
      pulmonary and three multiple and bilateral. In six of these patients a new
      disease recurrence was noted: four patients underwent further lung
      metastasectomy, but in all of them progression of the disease was observed. Mean
      survival of the population as a whole resulted as being 16 years (SE=1.4) with an
      actuarial survival of 77% at 5 years, 66% at 10 years and 56% at 15 years. Mean
      survival of patients having presented with distant metastases resulted as being
      11 years (SE=2.2). Mean survival after appearance of distant metastases resulted
      as being 72 months (SE=15.8) in the 9 patients treated by metastasectomy, and 62
      months (SE=15.1) in the 11 who did not have metastasis resection. CONCLUSIONS:
      Patients with adenoid cystic carcinoma could be frequently encountered with
      disease recurrence confined to the lung. The impact of complete lung metastasis
      resection on the course of the disease, however, is yet to be determined.

PMID- 18343150
TI  - Effect of phosphatidylglycerol depletion on the surface electric properties and
      the fluorescence emission of thylakoid membranes.
AB  - To explore the possible effect of phosphatidylglycerol (PG) on the surface
      electric properties and chlorophyll fluorescence characteristics we used electric
      light scattering technique and 77K chlorophyll fluorescence of thylakoid
      membranes from a cyanobacterium, Synechocystis PCC6803 (wild type) and its pgsA
      mutant defective in PG synthesis. We found a strong decrease in the permanent and
      induced electric dipole moments of the mutant thylakoids, following long-term PG
      depletion parallel with a decrease of the emission peak from PSI and an increase
      of the emission peak from PSII. Partial recovery of the electric state of
      thylakoid membranes was observed at re-addition of PG to the mutant cells
      depleted of PG for 21 days. This change in the electric dipole moments is
      probably due to a decrease in PG content and progressive structural alterations
      in the macroorganization of the photosynthetic complexes induced by PG
      deprivation. Our results suggest that the depletion of a lipid, which carries a
      negative charge, despite its small contribution to the overall lipid content,
      significantly perturbs the surface charge of the membranes. These changes are
      related with the chlorophyll fluorescence emission ratios of two photosystems and
      may partly explain our earlier results concerning the PG requirement for the
      function and assembly of photosystems I and II reaction centers.

PMID- 18343151
TI  - Tracking phototactic responses and modeling motility of Synechocystis sp. strain
      PCC6803.
AB  - The unicellular cyanobacterium Synechocystis sp. Strain PCC 6,803 exhibits
      phototaxis by moving along a surface towards a light source. This process
      requires Type IV pili and a phytochrome-like photoreceptor coupled to a complex
      signal transduction pathway. Cells progress through different phases of
      interaction before the development of finger-like projections moving in the
      direction of the light that are characteristic of phototaxis. To probe the
      interaction between individual cells during the initial phase of phototaxis we
      tracked and analyzed a large number of cells. We observed that individual cells
      have limited motility, but when cells divide and/or aggregate to attain a certain
      minimal group size, enhanced motility and phototaxis is observed. At the later
      stages of motility, there is noticeable phototactic behavior which results in the
      appearance of the finger-like projections. Our results indicate that cells prefer
      to move over areas previously traversed by other cells and confine themselves to
      these areas and that cells alter local surface characteristics allowing for
      enhanced motility. Based on cell tracking data we present a preliminary random
      walk model showing the forces that might interact to create the typical phases of
      phototaxis and motility. In this model, we can simulate the formation of finger
      like projections that are characteristic of phototaxis.

PMID- 18343152
TI  - Targeting AMPK: a new therapeutic opportunity in breast cancer.
AB  - BACKGROUND: This paper reviews the mammalian Target Of Rapamycin (mTOR) pathway
      dysregulation in breast cancer, and the current evidence targeting this pathway
      directly or through activation of AMP-activated protein kinase (AMPK) as an
      additional therapeutic opportunity for intervention in breast cancer. METHODS:
      Relevant articles were identified through computerised searches of Medline and
      Pubmed. Secondary articles were identified from the reference lists of key papers
      and by hand searching. RESULTS AND CONCLUSION: The current consensus to target
      the AMPK/mTOR pathway in breast cancer is based on in vitro and epidemiological
      evidences. A low incidence of cancer in diabetic patients on metformin has been
      explained in vitro by the drug's anti-proliferative effect through activation of
      AMPK. There is a need to explore the anticancer effects of metformin and the
      potential to develop the therapeutic avenues offered by targeting the AMPK/mTOR
      pathway.

PMID- 18343153
TI  - Suppressive effect of leflunomide on rat hepatic stellate cell proliferation
      involves on PDGF-BB-elicited activation of three mitogen-activated protein
      kinases.
AB  - In this manuscript, we demonstrated that following stimulus by Kupffer cell
      conditioned medium (KCM) and PDGF-BB, hepatic stellate cells (HSCs) showed
      significant increases in DNA synthesis and PDGFR-beta expression. Furthermore,
      phosphorylation of PDGFR-beta and three major members of the mitogen-activated
      protein kinase (MAPK) family were also significantly increased. Studies with
      respective neutralizing antibodies against released cytokines in conditioned
      medium demonstrated that PDGF-BB played an essential role in this complex
      activation process. Administration of A771726, leflunomide's metabolite, markedly
      blunted these effects. However, the combination of A771726 with any of the three
      MAPK inhibitors potentiated this inhibitory effect and showed completely blockage
      on PDGFR-beta expression and phosphorylation. Collectively, these data
      demonstrate that leflunomide inhibits KCM-mediated HSC proliferation via PDGFR
      beta phosphorylation and the subsequent activation of the MAPK pathway.
      Accordingly, targeted intervention against the PDGF-BB isoform may also offer a
      promising therapeutic approach to liver fibrosis.

PMID- 18343154
TI  - Mitogen activated protein kinase (MAPK) mediates non-genomic pathway of estrogen
      on T cell cytokine production following trauma-hemorrhage.
AB  - Although studies have shown 17beta-estradiol (E2) administration following trauma
      hemorrhage (T-H) attenuates alterations in T cell cytokine production, it remains
      unknown whether such effects of E2 are mediated via genomic or non-genomic
      pathways. In this study, we determined the non-genomic effects of E2 on splenic T
      cell cytokine production and the role of MAPK following T-H. Male Sprague-Dawley
      rats underwent T-H (mean BP 40 mmHg for 90 min, then resuscitation). E2, E2
      conjugated with BSA (E2-BSA, 1 mg/kg E2) with or without an estrogen receptor
      antagonist (ICI 182 780), or vehicle was administered during resuscitation. Two
      hours thereafter, T cell production of IL-2 and IFN-gamma and activation of MAPK
      (p38, ERK-1/2 and JNK) were determined. The effect of selective MAPK inhibitors
      on cytokine production was also examined in vitro. IL-2 and IFN-gamma production
      capacity and MAPK activation decreased in T cells following T-H. However, E2
      administration normalized these parameters. Although E2-BSA administration also
      attenuated suppression in cytokine production, the values were lower compared to
      sham. In contrast, E2-BSA prevented T-H-induced suppression in MAPK activation to
      the same extent as E2. Co-administration of ICI 182 780 abolished E2-BSA effects.
      These findings suggest E2 effects on T cell cytokine production following T-H are
      mediated at least in part via non-genomic pathway and these non-genomic effects
      are likely mediated via MAPK pathways.

PMID- 18343156
TI  - Isotopic labeling of c-type multiheme cytochromes overexpressed in E. coli.
AB  - Progresses made in bacterial genome sequencing show a remarkable profusion of
      multiheme c-type cytochromes in many bacteria, highlighting the importance of
      these proteins in different cellular events. However, the characterization of
      multiheme cytochromes has been significantly retarded by the numerous
      experimental challenges encountered by researchers who attempt to overexpress
      these proteins, especially if isotopic labeling is required. Here we describe a
      methodology for isotopic labeling of multiheme cytochromes c overexpressed in
      Escherichia coli, using the triheme cytochrome PpcA from Geobacter sulfurreducens
      as a model protein. By combining different strategies previously described and
      using E. coli cells containing the gene coding for PpcA and the cytochrome c
      maturation gene cluster, an experimental labeling methodology was developed that
      is based on two major aspects: (i) use of a two-step culture growth procedure,
      where cell growth in rich media was followed by transfer to minimal media
      containing (15)N-labeled ammonium chloride, and (ii) incorporation of the heme
      precursor delta-aminolevulinic acid in minimal culture media. The yields of
      labeled protein obtained were comparable to those obtained for expression of PpcA
      in rich media. Proper protein folding and labeling were confirmed by UV-visible
      and NMR spectroscopy. To our knowledge, this is the first report of a recombinant
      multiheme cytochrome labeling and it represents a major breakthrough for
      functional and structural studies of multiheme cytochromes.

PMID- 18343155
TI  - Increased expression of fibronectin and the alpha 5 beta 1 integrin in angiogenic
      cerebral blood vessels of mice subject to hypobaric hypoxia.
AB  - The extracellular matrix (ECM) is an important regulator of angiogenesis and
      vascular remodeling. We showed previously that angiogenic capillaries in the
      developing CNS express high levels of fibronectin and its receptor alpha5beta1
      integrin, and that this expression is developmentally downregulated. As cerebral
      hypoxia leads to an angiogenic response, we sought to determine whether
      angiogenic vessels in the adult CNS re-express fibronectin and the alpha5beta1
      integrin. Ten-week old mice were subject to hypobaric hypoxia for 0, 4, 7 and 14
      days, and fibronectin/integrin expression examined. Fibronectin and the alpha5
      integrin subunit were strongly upregulated on capillaries in the hypoxic CNS,
      with the effect maximal at the earliest time point examined (4 days).
      Immunofluorescent studies demonstrated that the alpha5 integrin was expressed by
      angiogenic endothelial cells. In light of the defined angiogenic role for
      fibronectin in other systems, this work suggests that induction of fibronectin
      alpha5beta1 integrin expression may be an important molecular switch driving
      angiogenesis in the hypoxic CNS.

PMID- 18343157
TI  - Chronic exposure to the parasite Enteromyxum leei (Myxozoa: Myxosporea) modulates
      the immune response and the expression of growth, redox and immune relevant genes
      in gilthead sea bream, Sparus aurata L.
AB  - The myxosporean parasite Enteromyxum leei invades the intestine of gilthead sea
      bream producing a slow-progressing disease, which may end in the death of fish.
      The present work aimed to better know the host immune response and the underlying
      molecular mechanisms, which may help to understand why some individuals seem to
      be refractory to the disease. Three main aspects involved in fish health and
      welfare (immune, growth and redox status) were studied in fish exposed to E. leei
      contaminated effluent, in comparison with control animals (not exposed to the
      disease). After chronic exposure (113days), prevalence of infection was 67.8%.
      Among exposed fish, parasitized and non-parasitized fish exhibited clear
      differences in some of the measured innate immune factors (respiratory burst,
      serum peroxidases, lysozyme and complement), and in the expression of immune,
      antioxidant and GH-related genes. The respiratory burst of parasitized fish was
      significantly higher, and serum peroxidases and lysozyme were significantly
      decreased both in parasitized and non-parasitized fish. The gene expression of
      GHR-I, GHR-II, IGF-I and IGF-II was measured in head kidney (HK) samples, and
      that of interleukin (IL)-1beta, tumour necrosis factor (TNF)-alpha, alpha-2M, GR,
      GPx-1 and GRP-75 was measured in intestine and HK samples, by rtqPCR. Parasitized
      fish exhibited a down-regulation of IL-1beta, TNF-alpha and GPx-1 in the
      intestine, and GHR-I and IGF-I were also down regulated in HK. alpha-2M and GRP
      75 were over-expressed in the intestine of parasitized animals. Non-parasitized
      fish had increased transcripts of GHR-I and IGF-I with respect to control
      animals, which could furnish their immunocytes with an advantage to combat the
      parasite. The expression of GHR-II and IGF-II was not altered by the parasite
      challenge.

PMID- 18343158
TI  - Assessment of functional recovery in tennis elbow.
AB  - OBJECTIVES: (a) To investigate changes in muscular strength, fatigue and activity
      in recovered tennis elbow (RTE); (b) to assess the appropriateness of EMG and
      strength measurements in monitoring functional recovery in tennis elbow (TE).
      METHODS: Study included three age-matched female groups of Control (C) (n=8, no
      history of musculoskeletal problems), TE (n=7, local tenderness at the lateral
      epicondyle and pain with resisted wrist and middle finger extension) and RTE
      (n=6, asymptomatic for at least 6 months, no lateral epicondyle tenderness).
      Measurements included metacarpophalangeal (MCP), wrist, shoulder and grip
      isometric strength and EMG measures of muscle fatigue and activity for five
      forearm muscles (wrist extensors and flexors). RESULTS: Strength was greater
      (p<0.05) for all measurements in C compared to RTE and TE except for MCP
      extension. Only MCP extension was stronger in RTE than TE. EMG revealed increased
      activity of extensor carpi radialis (ECR) in RTE, decreased in TE. CONCLUSIONS:
      Despite attenuation of pain, global upper limb weakness in RTE indicated
      incomplete functional recovery. Increased strength of MCP extension may protect
      weakened wrist extensors from further injury. Monitoring the ECR activity as well
      as strength measurements may provide a useful assessment of functional recovery
      in TE.

PMID- 18343159
TI  - Detection and scaling of task-induced fMRI-BOLD response using resting state
      fluctuations.
AB  - This study evaluated a calibration technique for scaling the fMRI-BOLD response
      during a simple motor task. A novel scaling parameter, resting state
      physiological fluctuation amplitude (RSFA), was tested using previously
      established scaling factors such as breath hold or 5% CO(2). RSFA was
      hypothesized to contain vascular reactivity information present in the resting
      state fMRI signal. Subjects were scanned under various stimulus conditions: (a)
      rest while breathing room air, (b) bilateral fingertapping, (c) breath holding
      and (d) moderate hypercapnia (breathing 5% CO(2)+air). In all subjects who
      breathed 5% CO(2), RSFA correlated highly with the BOLD response amplitude during
      5% CO(2) inhalation. Also, RSFA correlated highly with the amplitude of the BOLD
      response elicited by breath hold. RSFA was therefore used as a hemodynamic
      scaling factor to calibrate both the amplitude and spatial extent of the fMRI
      BOLD response during the motor task (fingertapping). Results revealed that
      amplitude scaling using RSFA was similar to that using breath hold or 5% CO(2),
      where the spatial extent of activation diminished by 20-37% over all subjects.
      Spatial extent of activation changed significantly after scaling and only 30-40%
      of the activated area overlapped with the unscaled activation. RSFA-scaled task
      induced fMRI-BOLD response in both amplitude and spatial extent was comparable to
      that obtained using breath hold or 5% CO(2). We conclude that RSFA may be used to
      hemodynamically scale the fMRI-BOLD response and does not require the use of a
      hypercapnic challenge (which may not be purely non-neural), which can be
      difficult to implement in special populations.

PMID- 18343160
TI  - Hypothermia effects on neurovascular coupling and cerebral metabolic rate of
      oxygen.
AB  - Neuronal activation is accompanied by a local increase in cerebral blood flow
      (CBF) and in cerebral metabolic rate of oxygen (CMRO(2)), caused by neurovascular
      and neurometabolic coupling. Hypothermia is used as a neuroprotective approach in
      surgical patients and therapeutically after cardiac arrest or stroke. The effect
      of hypothermia on neurovascular coupling is of interest for evaluating brain
      function in these patients, but has not been determined so far. It is not clear
      whether functional hyperaemia actually operates at subnormal temperatures. In
      addition, decreasing brain temperature reduces spontaneous CMRO(2) following a
      known quantitative relationship (Q(10)). Q(10) determination may serve to
      validate a recently introduced CMRO(2) measurement approach relying on optical
      measurements of CBF and hemoglobin concentration. We applied this method to
      investigate hypothermia in a functional study of the somatosensory cortex.
      Anesthetized Wistar rats underwent surgical implantation of a closed cranial
      window. Using laser Doppler flowmetry and optical spectroscopy, relative changes
      in CBF and hemoglobin concentration were measured continuously. At the same time,
      an electroencephalogram (EEG) was recorded from the measurement site. By the
      application of ice packs, whole-body hypothermia was induced, followed by
      rewarming. Spontaneous EEG, CBF and CMRO(2) were measured, interleaved by blocks
      of electrical forepaw stimulation. The Q(10) obtained from spontaneous CMRO(2)
      changes of 4.4 (95% confidence interval 3.7-5.1) was close to published values,
      indicating the reliability of the CMRO(2) measurement. Lowering brain temperature
      decreased functional changes of CBF and CMRO(2) as well as amplitudes of
      somatosensory evoked potentials (SEP) to the same degree. In conclusion,
      neurovascular and neurometabolic coupling is preserved during hypothermia.

PMID- 18343161
TI  - Differential sensitivity for viewpoint between familiar and unfamiliar faces in
      human visual cortex.
AB  - People are extremely proficient at recognizing faces that are familiar to them,
      but are poor at identifying unfamiliar faces. We used fMR-adaptation to ask
      whether this difference in recognition might be reflected in the relative
      viewpoint-dependence of face-selective regions in the brain. A reduced response
      (adaptation) to repeated images of unfamiliar or familiar faces was found in the
      fusiform face area (FFA), but not in the superior temporal sulcus (STS) face
      selective region. To establish if the neural representation of faces was
      invariant to changes in viewpoint, we parametrically varied the viewing angle of
      successive images using 3-dimensional models of unfamiliar and familiar faces. We
      found adaptation to familiar faces across all changes in viewpoint in the FFA. In
      contrast, a release from adaptation was apparent in the FFA when unfamiliar faces
      were viewed at increasing viewing angles. These results provide a neural basis
      for differences in the recognition of familiar and unfamiliar faces.

PMID- 18343163
TI  - Experience-dependent neural substrates involved in vocal pitch regulation during
      singing.
AB  - Proper singing requires the integration of auditory feedback mechanisms with the
      vocal motor system, such that vocal pitch can be precisely controlled. To
      determine the neural substrates involved in audio-vocal integration, non
      musicians and experienced singers underwent fMRI scanning while they sang a
      single tone with either unaltered ("simple") or pitch-shifted auditory feedback;
      in pitch-shifted trials, subjects were instructed either to ignore or compensate
      for the shifted feedback. We hypothesized that the anterior cingulate cortex
      (ACC), superior temporal gyrus (STG), and anterior insula may be involved in
      audio-vocal integration due to their functional roles during singing and their
      anatomical connectivity. Although singers were more accurate than non-musicians
      in simple singing, both groups recruited similar functional networks. Singers
      ignored the shifted feedback better than non-musicians, and both groups also
      displayed different patterns of neural activity for this task: singers recruited
      bilateral auditory areas and left putamen, while non-musicians recruited the left
      supramarginal gyrus and primary motor cortex. While there were no significant
      group differences in performing the compensate task, singers displayed enhanced
      activity in the ACC, superior temporal sulcus, and putamen, whereas non-musicians
      exhibited increased activity in the dorsal premotor cortex, a region involved
      with sensorimotor interactions. We propose two neural substrates for audio-vocal
      integration: the dorsal premotor cortex may act as a basic interface, but with
      vocal training and practice, the ACC, auditory cortices, and putamen may be
      increasingly recruited as people learn to monitor their auditory feedback and
      adjust their vocal output accordingly.

PMID- 18343162
TI  - The micro-architecture of the cerebral cortex: functional neuroimaging models and
      metabolism.
AB  - In order to interpret/integrate data obtained with different functional
      neuroimaging modalities (e.g. fMRI, EEG/MEG, PET/SPECT, fNIRS), forward
      generative models of a diversity of brain mechanisms at the mesoscopic level are
      considered necessary. For the cerebral cortex, the brain structure with possibly
      the most relevance for functional neuroimaging, a variety of such biophysical
      models has been proposed over the last decade. The development of technological
      tools to investigate in vitro the physiological, anatomical and biochemical
      principles at the microscopic scale in comparative studies formed the basis for
      such theoretical progresses. However, with the most recent introduction of
      systems to record electrical (e.g. miniaturized probes chronically/acutely
      implantable in the brain), optical (e.g. two-photon laser scanning microscopy)
      and atomic nuclear spectral (e.g. nuclear magnetic resonance spectroscopy)
      signals using living laboratory animals, the field is receiving even greater
      attention. Major advances have been achieved by combining such sophisticated
      recording systems with new experimental strategies (e.g. transgenic/knock-out
      animals, high resolution stereotaxic manipulation systems for probe-guidance and
      cellular-scale chemical-delivery). Theoreticians may now be encouraged to re
      consider previously formulated mesoscopic level models in order to incorporate
      important findings recently made at the microscopic scale. In this series of
      reviews, we summarize the background at the microscopic scale, which we suggest
      will constitute the foundations for upcoming representations at the mesoscopic
      level. In this first part, we focus our attention on the nerve ending particles
      in order to summarize basic principles and mechanisms underlying cellular
      metabolism in the cerebral cortex. It will be followed by two parts highlighting
      major features in its organization/working-principles to regulate both cerebral
      blood circulation and neuronal activity, respectively. Contemporary theoretical
      models for functional neuroimaging will be revised in the fourth part, with
      particular emphasis in their applications, advantages/limitations and future
      prospects.

PMID- 18343164
TI  - Epidemiology of hip and knee pain in a community based sample of Italian persons
      aged 65 and older.
AB  - OBJECTIVE: To describe prevalence, characteristics and correlates of hip pain
      (HP) and knee pain (KP) in an Italian community based cohort aged 65 and older
      (65+). METHOD: Baseline survey (1998-2000), population-based study in the Chianti
      area (Tuscany, Italy); 1299 persons aged 65+ were selected from the city registry
      of Greve in Chianti and Bagno a Ripoli (multistage sampling method); 1006
      participants (564 women and 442 men, age 75.2+/-7.1) provided information for
      this analysis. Persons reporting HP/KP in the past 4 weeks were recorded and
      their Western Ontario and McMaster University Osteoarthritis Index pain score
      (WPS-range 0-20) calculated. Potential correlates of HP/KP, including clinical,
      lifestyle and psycho-social features and physical measures, were tested in age-
      and gender-adjusted regression analyses and then entered a multivariate
      regression model. RESULTS: HP was reported by 11.9% participants, while 22.4%
      reported KP and 7.2% both conditions. Climbing/descending stairs and walking were
      the activities eliciting more severe pain in either condition. Average WPSs were
      5.6+/-3.5 for HP and 5.4+/-10.4 for KP. Both HP and KP were related to back pain,
      reduced hip abduction, reduced muscle power and increased trunk flexibility. HP
      was also related to KP and poor self-rated health (SRH), while KP to HP, foot
      pain, high body mass index, reduced knee passive flexion and knee extension
      torque, low education. CONCLUSION: In a community sample of an Italian persons
      aged 65+, the prevalence of KP almost doubled that of HP. While both conditions
      were related to pain in other joints and specific joint impairment, only HP was
      related to poor SRH, and only KP to mechanical overload.

PMID- 18343165
TI  - Effects of tyrosine kinase and phosphatase inhibitors on microtubules in
      Arabidopsis root cells.
AB  - To investigate the role of tyrosine phosphorylation/dephosphorylation processes
      in plant cells the morphology of Arabidopsis thaliana primary roots and the
      organization of cortical microtubules (MTs) were studied after inhibition of
      protein tyrosine kinases (PTKs) and tyrosine phosphatases (PTPs). It was found
      that all tested types of PTKs inhibitors (herbimycin A, genistein and tyrphostin
      AG 18) altered root hair growth and development, probably as a result of their
      significant influences on MTs organization in root hairs. The treatment also led
      to MTs reorientation and disruption in epidermis and cortex cells of both
      elongation and differentiation zones of primary roots. Enhanced tyrosine
      phosphorylation after treatment with a PTPs inhibitor (sodium orthovanadate)
      resulted in intense induction of root hair development and growth and caused a
      significant shortening of the elongation zone. It also led to changes of MTs
      orientation from transverse to longitudinal in epidermis and cortex cells of the
      elongation and differentiation zones of the root. From the data obtained we can
      suppose that tyrosine phosphorylation can be involved in the dynamics and
      organization of MTs in different types of plant cells.

PMID- 18343166
TI  - Effects of the herbicide isopropyl-N-phenyl carbamate on microtubules and MTOCs
      in lines of Nicotiana sylvestris resistant and sensitive to its action.
AB  - To clarify the mechanism of isopropyl-N-phenyl carbamate (IPC) action on higher
      plant cells the sensitivity of microtubules (cortical network and mitotic arrays)
      and microtubule organizing centers to IPC treatment (30 microM) in IPC-resistant
      and sensitive Nicotiana sylvestris lines was studied. It was clearly demonstrated
      that IPC does not depolymerize plant MTs but causes the MTOC damage in cells,
      which results in MTOC fragmentation, splitting of the spindle poles and in
      abnormal division spindle formation. It was also found that IPC-resistance of
      mutant N. sylvestris line correlates not with tubulin resistance to IPC action
      but possibly with resistance of one of the proteins involved in MTOC composition.

PMID- 18343167
TI  - The annual meeting of the European Society for Vascular Surgery--the scientific
      contents over the years.
AB  - AIM AND METHOD: to analyze the presentations given at the annual meeting of
      European Society for Vascular Surgery: topic, geographical distribution, later
      publication. Three six-year periods from 1989 have been evaluated. RESULTS: case
      series dominates but randomized trials have increased somewhat. Papers on animal
      experiments and basic science have decreased. The most frequently reported
      diseases have been aortic aneurysm, carotid artery problems, lower extremity
      ischaemia and with an increasing number of papers on venous disease. Around two
      thirds of the presentations have been later published as full papers in European
      Journal of Vascular and Endovascular Surgery, but as many as one quarter has not
      been published. Geographical origin has varied over time with a decrease in the
      UK dominance. CONCLUSION: The presentations at the Annual meeting of European
      Society for Vascular Surgery contribute substantially to the contents of the
      Society Journal but a large proportion of the presentations never appear in
      print. Northern Europe dominates when papers per population unit is counted.

PMID- 18343168
TI  - A comparison of the complication rates following unilateral and bilateral
      varicose vein surgery.
AB  - OBJECTIVE: To compare the complication rates of unilateral and bilateral varicose
      vein surgery. DESIGN: Observational clinical study with prospective data
      collection. SETTING: Southport and Ormskirk Hospital NHS Trust. SUBJECTS: 1090
      patients undergoing varicose vein surgery during the period January 2002-June
      2005. 695 (64%) of these had unilateral surgery and 395 (36%) had bilateral
      surgery giving a total of 1485 legs operated on (47% as a unilateral operation
      and 53% as a bilateral operation). RESULTS: 43/695 (6.2%) of patients who
      underwent unilateral surgery and 34/395 (8.6%) of patients who underwent
      bilateral surgery developed a wound infection. 77/695 (11%) of patients who
      underwent unilateral surgery developed paraesthesia compared to 81/395 (21%) for
      bilateral surgery. 2/695 (0.13%) unilateral surgery patients and no bilateral
      surgery patients developed neuralgia. Residual varicose veins were present in
      30/695 (4.3%) of unilateral group and 32/395 (8.1%) of the bilateral group. 1/695
      (0.14%) of unilateral surgery patients and 3/395 (0.75%) of bilateral surgery
      patients developed DVTs. Comparing limbs, a complication of any type was seen in
      153/695 (22%) limbs treated by unilateral surgery and 150/790 (19% N.S., Chi
      squared) limbs treated by bilateral surgery. CONCLUSION: Complications following
      varicose vein surgery appear to be more common following bilateral procedures.
      However, the complication rate per limb is similar for unilateral and bilateral
      operations.

PMID- 18343169
TI  - Intraoperative retrograde mesenteric angioplasty for acute occlusive mesenteric
      ischaemia: a case series.
AB  - Acute mesenteric ischaemia secondary to atherosclerotic disease of the superior
      mesenteric artery is a surgical emergency associated with a poor prognosis, and
      requires prompt diagnosis and early revascularisation in order to improve
      outcome. The traditional management of surgical resection of necrotic bowel plus
      mesenteric revascularisation by surgical bypass is associated with significant
      morbidity and mortality. We describe the use of a combined surgical and
      endovascular approach, using intraoperative retrograde superior mesenteric
      angioplasty at the time of laparotomy. Four patients have been treated by this
      combined technique with three surviving, although one subsequently required an
      open surgical revascularisation procedure.

PMID- 18343170
TI  - Transitions between epithelial and mesenchymal states in development and disease.
AB  - The ancestors of modern Metazoa were constructed in large part by the foldings
      and distortions of two-dimensional sheets of epithelial cells. This changed
      approximately 600 million years ago with the evolution of mesenchymal cells.
      These cells arise as the result of epithelial cell delamination through a
      reprogramming process called an epithelial to mesenchymal transition (EMT) [Shook
      D, Keller R. Mechanisms, mechanics and function of epithelial-mesenchymal
      transitions in early development. Mech Dev 2003;120:1351-83; Thiery JP, Sleeman
      JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol
      Cell Biol 2006;7:131-42]. Because mesenchymal cells are free to migrate through
      the body cavity, the evolution of the mesenchyme opened up new avenues for
      morphological plasticity, as cells evolved the ability to take up new positions
      within the embryo and to participate in novel cell-cell interactions; forming new
      types of internal tissues and organs such as muscle and bone [Thiery JP, Sleeman,
      JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol
      Cell Biol 2006;7:131-42; Hay ED, Zuk A. Transformations between epithelium and
      mesenchyme: normal, pathological, and experimentally induced. Am J Kidney Dis
      1995;26:678-90]. After migrating to a suitable site, mesenchymal cells coalesce
      and re-polarize to form secondary epithelia, in a so-called mesenchymal
      epithelial transition (MET). Such switches between mesenchymal and epithelial
      states are a frequent feature of Metazoan gastrulation [Hay ED, Zuk A.
      Transformations between epithelium and mesenchyme: normal, pathological, and
      experimentally induced. Am J Kidney Dis 1995;26:678-90] and the neural crest
      lineage [Duband JL, Monier F, Delannet M, Newgreen D. Epitheliu-mmesenchyme
      transition during neural crest development. Acta Anat 1995;154:63-78].
      Significantly, however, when hijacked during the development of cancer, the
      ability of cells to undergo EMT, to leave the primary tumor and to undergo MET at
      secondary sites can have devastating consequences on the organism, allowing tumor
      cells derived from epithelia to invade surrounding tissues and spread through the
      host [Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal
      transitions. Nat Rev Mol Cell Biol 2006;7:131-42; Hay ED, Zuk A. Transformations
      between epithelium and mesenchyme: normal, pathological, and experimentally
      induced. Am J Kidney Dis 1995;26:678-90]. Thus, the molecular and cellular
      mechanisms underpinning EMT are both an essential feature of Metazoan development
      and an important area of biomedical research. In this review, we discuss the
      common molecular and cellular mechanisms involved in EMT in both cases.

PMID- 18343171
TI  - Multicellular dynamics during epithelial elongation.
AB  - The reorganization of multicellular populations to produce an elongated tissue
      structure is a conserved mechanism for shaping the body axis and several organ
      systems. In the Drosophila germband epithelium, this process is accompanied by
      the formation of a planar polarized network of junctional and cytoskeletal
      proteins in response to striped patterns of gene expression. Actomyosin cables
      and adherens junctions are dynamically remodeled during intercalation, providing
      the basis for polarized cell behavior. Quantitative analysis of cell behavior in
      living embryos reveals unexpected cell population dynamics that include the
      formation of multicellular rosette structures as well as local neighbor exchange.

PMID- 18343172
TI  - The monitoring, prevention and treatment of sub-acute ruminal acidosis (SARA): a
      review.
AB  - Sub-acute ruminal acidosis (SARA) has become an increasing problem in well
      managed, high yielding dairy herds and the monitoring of groups of cows for signs
      of the condition is now crucial. Rumenocentesis may be ethically questionable but
      the technique remains the most reliable means of diagnosing SARA. Continuous
      measurement of ruminal pH may however be possible in the future. Parameters
      reflecting the metabolic acidosis caused by SARA are also promising tools, and
      measurement of milk fat content may be useful in individual mid-lactation cows
      although it is less valuable for bulk tank milk samples. The prevention of SARA
      includes the establishment of feeding and management guidelines seeking to
      minimize rumen acidotic load. Regular monitoring may facilitate early recognition
      of the condition and limit economic losses. Some degree of SARA may however be
      inevitable and presents a challenge to the dairy industry as consumers become
      increasingly concerned about the welfare of production animals.

PMID- 18343173
TI  - Aicardi-Goutieres syndrome (AGS).
AB  - In 1984, Jean Aicardi and Francoise Goutieres described 8 children showing both
      severe brain atrophy and chronic cerebrospinal fluid lymphocytosis, with basal
      ganglia calcification in at least one member of each affected family. The course
      was rapid to death or a vegetative outcome. Aicardi and Goutieres correctly
      predicted that the disorder would be genetic, but emphasised that "some features,
      especially the pleocytosis, may erroneously suggest an inflammatory condition".
      The increased interferon-alpha in affected children (Pierre Lebon, Paris)
      mimicked congenital viral infection, but the associated chilblains (pernio)
      pointed to lupus erythematosus and an autoimmune mechanism. Genetic research led
      by Yanick Crow has clarified these puzzling relationships in Aicardi-Goutieres
      syndrome, a syndrome that now includes conditions previously known as
      microcephaly-intracranial calcification syndrome, pseudo-TORCH and Cree
      encephalitis. At the time of writing, Crow's team has discovered that over 80% of
      families with Aicardi-Goutieres syndrome have mutations in one of four nuclease
      genes, the exonuclease TREX1 and the genes for all three subunits of the
      ribonuclease H2 enzyme complex. Aicardi-Goutieres syndrome is both genetically
      and phenotypically heterogeneous, with a range of severity from life-threatening
      perinatal illness to mild late infancy onset. All infants of whatever genotype
      have increased interferon-alpha in the first year of life and this appears to be
      the final common pathway that links Aicardi-Goutieres syndrome, congenital virus
      infection and systemic lupus erythematosus.

PMID- 18343174
TI  - Open-label, long-term safety study of zonisamide administered to children and
      adolescents with epilepsy.
AB  - BACKGROUND: Zonisamide is licensed in the EU and USA for the adjunctive treatment
      of partial-onset seizures in adults but there are few data about its use in
      children. AIMS: To assess the long-term safety and efficacy of zonisamide in
      children and adolescents. METHODS: Zonisamide-naive patients (n=109, aged 3-15
      years, weight >or=12.5 kg) with a clinical diagnosis of epilepsy (>or=4
      seizures/month, receiving 1-2 antiepileptic drugs [AEDs] daily) received
      zonisamide once or twice daily in an open-label trial. The starting dose was
      1mg/kg/day, increased by 2 mg/kg/day every 1-2 weeks at the investigator's
      discretion to an initial maximum of 12 mg/kg/day. The occurrence of adverse
      events (AEs) was the primary safety measure. Efficacy was measured via the
      reductions in seizure frequency and via investigator- and carer-rated global
      assessment ratings. RESULTS: The mean dose received was 8.5 mg/kg/day. Of the 109
      children, 52 (48%) completed 15 months' treatment. Treatment-related AEs, mostly
      mild-to-moderate in severity, were reported by 58 patients. Seven patients
      discontinued due to treatment-related AEs. Serious AEs (pancreatitis, decreased
      sweating, and vertigo) were reported by three patients. A significant (p=0.033)
      median reduction in 'all seizure' frequency of 2.60 seizures per week was
      observed. Additionally, a significant (p=0.029) median reduction of 1.80
      seizures/week in 'complex partial' seizures was reported. Improvements in
      investigator- and carer-rated global assessments were noted. CONCLUSIONS:
      Zonisamide treatment was generally well tolerated and was associated with
      significant reductions in seizure frequency in this pediatric population with a
      variety of both partial and generalized medically refractory epilepsy syndromes.

PMID- 18343175
TI  - 2D-REFINE spectroscopy: separation of overlapping hyperfine spectra.
AB  - We show on a mixture of three spectrally overlapping paramagnetic compounds
      TEMPO, BDPA and CuHis that it is possible to separate their field-swept and
      hyperfine spectra based on the difference in their longitudinal relaxation times
      T1. This was achieved in a two-dimensional experiment, where one dimension
      corresponds to the spectral domain and the second dimension encodes the
      relaxation behavior of the individual compound. Inverse Laplace Transform with
      respect to this domain separates the field-swept and hyperfine spectra of the
      individual compounds in the relaxation rate domain. This extends our formerly
      proposed Relaxation Filtered Hyperfine (REFINE) method to be applicable to more
      than two spectrally overlapping spectra by adding a further dimension to the
      chosen EPR experiment.

PMID- 18343176
TI  - Effect of protein convertase subtilisin/kexin type 9 (PCSK9) 46L gene
      polymorphism on LDL cholesterol concentration in a Polish adult population.
AB  - The purpose was to study the effect of PCSK9 46L on cholesterol concentration and
      cardiovascular morbidity. By comparing 176 carriers with 6618 non-carriers
      identified through a cross-sectional population study (WOBASZ) we confirmed the
      LDL lowering effect of PCSK9 46L and demonstrated that it increases with the
      concentration of LDL. We noted that PCSK9 46L was associated with tendency for
      protection from myocardial infarction but not stroke suggesting a difference in
      the effect on susceptibility to these disorders.

PMID- 18343177
TI  - n of 1 trial for an ornithine transcarbamylase deficiency carrier.
AB  - Ornithine transcarbamylase deficiency (OTCD) is an X-linked disorder of the urea
      cycle. It is often fatal in affected males. Treatment for affected individuals
      includes dietary protein restriction, activation of alternative pathways of
      nitrogen excretion and L-arginine supplementation. Depending on the amount of X
      chromosome inactivation skewing, females show variable clinical manifestations,
      and sometimes the need for treatment, including medications, is unclear. We
      conducted an n of 1 randomized controlled trial on an obligate OTC carrier. The
      treating physician and patient were blinded to treatment. Either placebo capsules
      or L-arginine capsules were given for weekly periods. Weekly efficacy indicators
      included plasma arginine and glutamine levels and a quality of life/mood
      assessment questionnaire scale. Clear evidence of benefit with L-arginine
      compared to placebo was shown. This is the first time an n of 1 randomized
      controlled trial has been reported for an X-linked metabolic condition. Despite
      some logistic hurdles, we have demonstrated that this method was an effective
      tool for determining the value of treatment. We propose that other rare metabolic
      conditions may be amenable to such trials, if the benefit of treatment is in
      doubt.

PMID- 18343178
TI  - Measurement of systolic and diastolic arterial wall shear stress in the ascending
      aorta.
AB  - PURPOSE: Wall shear stress (WSS) appears to contribute significantly in the
      initiation and progression of atherosclerotic disease. The purpose of this work
      is to present in vivo systolic and diastolic WSS calculations in the human
      ascending aorta by the application of three straightforward methodologies based
      on Poiseuille's theory of flow. MATERIALS AND METHODS: Blood flow measurements
      were performed retrospectively in the ascending aorta of 20 non-atherosclerotic
      patients using phase-contrast MRI. WSS calculations were performed assuming
      Poiseuille's theory of flow based on average flow volume, average flow velocity
      and maximum flow velocity. Systolic and diastolic WSS values were calculated and
      compared with the calculated maximum and minimum values of WSS throughout the
      cardiac cycle. RESULTS: Systolic WSS values calculated by average flow volume,
      average flow velocity and maximum flow velocity were similar (0.4+/-0.2N/m(2),
      0.4+/-0.3N/m(2)and 0.4+/-0.2N/m(2), respectively). Diastolic WSS values
      calculated by maximum flow velocity were significantly higher (11.6+/-7.0x10(
      2)N/m(2)) compared to values calculated by average flow volume (0.3+/-0.9x10(
      2)N/m(2)) and average flow velocity (0.3+/-1.0x10(-2)N/m(2)). Comparison of
      systolic and diastolic WSS values with maximum and minimum WSS values showed that
      time instances of maximum and minimum blood flow velocities do not coincide with
      time instances of maximum and minimum blood flow volume. CONCLUSION: In vivo
      calculation of WSS in the ascending aorta is feasible by phase-contrast MRI flow
      measurements and straightforward methodologies based on Poiseuille's theory of
      flow. However, measurements based on maximum flow velocity show larger deviations
      compared to measurements based on mean flow volume or mean flow velocity.

PMID- 18343179
TI  - The promise of new PET image reconstruction.
AB  - Image reconstruction in positron emission tomography (PET) is conventionally
      regarded as the algorithm applied to the acquired data to produce images used for
      estimation of physiological parameters, or to determine the presence of disease.
      There are numerous approaches to image reconstruction, and the method chosen has
      a significant impact on the utility of PET. The use of iterative image
      reconstruction algorithms and the use of resolution modelling ("resolution
      recovery") are two specific advances from recent years which have demonstrated
      marked improvements in image quality. This paper considers three main aspects of
      PET image reconstruction in which there are still promising possibilities for
      further advance: (i) full consideration of the raw acquired PET data (with
      minimal pre-processing), (ii) careful selection of the parameters to estimate and
      (iii) accurate definition of the system matrix, which maps the parameters to the
      measurement space. Specific examples for these three areas include (i) the full
      use of timing, position and energy information, (ii) selecting physiological
      parameters as the unknowns to estimate and (iii) using Monte Carlo simulation to
      model the PET scanner and patient, in conjunction with time-dependent MRI or CT
      anatomical information to render the model more accurate. Present computational
      constraints mean that limited but practical methods have to be used, which to
      some extent compromise the full capabilities of image reconstruction in all of
      the aforementioned areas of promise. Nonetheless, this paper comments on possible
      ways forward without being overly concerned about the current limitations.

PMID- 18343180
TI  - Dermatologic conditions of the ill returned traveler: an analysis from the
      GeoSentinel Surveillance Network.
AB  - BACKGROUND: Skin disorders are common in travelers. Knowledge of the relative
      frequency of post-travel-related skin disorders, including their geographic and
      demographic risk factors, will allow for effective pre-travel counseling, as well
      as improved post-travel diagnosis and therapeutic intervention. METHODS: We
      performed a retrospective study using anonymous patient demographic, clinical,
      and travel-related data from the GeoSentinel Surveillance Network clinics from
      January 1997 through February 2006. The characteristics of these travelers and
      their itineraries were analyzed using SAS 9.0 statistical software. RESULTS: A
      skin-related diagnosis was reported for 4594 patients (18% of all patients seen
      in a GeoSentinel clinic after travel). The most common skin-related diagnoses
      were cutaneous larva migrans (CLM), insect bites including superinfected bites,
      skin abscess, and allergic reaction (38% of all diagnoses). Arthropod-related
      skin diseases accounted for 31% of all skin diagnoses. Ill travelers who visited
      countries in the Caribbean experienced the highest proportionate morbidity due to
      dermatologic conditions. Pediatric travelers had significantly more dog bites and
      CLM and fewer insect bites compared with their adult counterparts; geriatric
      travelers had proportionately more spotted fever and cellulitis. CONCLUSIONS:
      Clinicians seeing patients post-travel should be alert to classic travel-related
      skin diseases such as CLM as well as more mundane entities such as pyodermas and
      allergic reactions. To prevent and manage skin-related morbidity during travel,
      international travelers should avoid direct contact with sand, soil, and animals
      and carry a travel kit including insect repellent, topical antifungals, and
      corticosteroids and, in the case of extended and/or remote travel, an oral
      antibiotic with ample coverage for pyogenic organisms.

PMID- 18343181
TI  - Parkinson's disease and functional decline in older Mexican Americans.
AB  - The purpose of this study was to establish prevalence and five-year incidence,
      and explore functional decline among older Mexican Americans with Parkinson's
      disease (PD). Using data from the Hispanic EPESE, baseline characteristics were
      compared across PD response profiles. Weighted generalized estimating equations
      (GEE) modeled the association between PD and outcomes. Prevalence was 1.30%;
      incidence at wave 4 was 1.18%. Those with prevalent PD had worse function than
      those without PD at each wave. Progressive functional decline across time was
      observed among those with PD. Older Mexican Americans with PD often live in the
      community, and those who provide care for them may be overburdened.

PMID- 18343182
TI  - Frequency and significance of vocalizations in Sydenham's chorea.
AB  - Sydenham's chorea (SC) is a complication of Streptococcus infection characterized
      by a combination of motor and non-motor features. We have investigated the
      presence of vocalizations in 89 consecutive patients with SC evaluated during a
      one-year period in the UFMG Movement Disorders Clinic. Seven (4/3 M/F) of the 89
      patients (29/60 M/F) presented with simple vocalizations not preceded by
      premonitory sensations but in association with facial chorea in five patients.
      These findings suggest that vocalizations are not a common feature in SC and
      their phenomenology is quite distinct from the characteristics of vocal tics in
      tic disorders.

PMID- 18343183
TI  - The activation and physiological functions of the proprotein convertases.
AB  - The mammalian secretory proprotein convertases are part of a family of nine
      serine proteinases of the subtilisin-type. Seven of them cleave after basic amino
      acids and are called PC1/3, PC2, furin, PC4, PC5/6, PACE4 and PC7. The two other
      convertases SKI-1/S1P and PCSK9 are implicated in cholesterol and/or fatty acid
      metabolism. The convertases PC5/6 and PACE4 are activated at the cell surface
      where they are tethered to heparan sulfate proteoglycans. This activation pathway
      is unique and differs from that of furin and PC7, which are activated in the
      trans-Golgi network and from PC1/3 and PC2 that are activated in dense core
      secretory granules. While some of the basic amino acid-specific convertases may
      display redundant cleavages of substrates, they uniquely process certain
      substrates in vivo. Indeed, the conditional knockout of the PC5/6 gene in the
      embryo proper in mice led to severe malformations, bone morphogenic defects and
      death at birth. This is likely due to the absence of processing of the growth
      differentiating factor 11 (Gdf11). Both complete and liver-specific knockout of
      Pcsk9 revealed that it is a major convertase that regulates the level of
      circulating low-density lipoproteins (LDL) via the degradation of the hepatic LDL
      receptor. This apparently non-enzymatic mechanism implicates the enhanced
      degradation of the LDLR in endosomes/lysosomes. These data provide evidence that
      an inhibitor of PCSK9-LDLR interaction is a viable target for the development of
      a novel cholesterol lowering drug in conjunction with the classical statins.

PMID- 18343184
TI  - Corneal stability after discontinued soft contact lens wear.
AB  - PURPOSE: To determine the time needed to reach corneal stability after
      discontinued daily wear of soft contact lenses and to identify corneal
      topographic and pachymetric changes during this period. METHODS: We prospectively
      studied the eyes of 21 consecutive soft contact lens wearers evaluated for
      keratorefractive surgery. Each eye was examined once immediately after lens
      removal, 3 and 7 days later, and weekly thereafter. At each visit, manifest
      refraction, keratometry, corneal topography (EyeSys Corneal Analysis system,
      EyeSys Laboratories, Houston, TX) and pachymetry were performed. Incidence of
      associated corneal warpage and changes in corneal curvature and thickness during
      corneal stability time were determined. RESULTS: Of the 42 eyes examined, 26
      corneas showed no significant change after the initial evaluation (stable group).
      The minimum stability time was 3 days in the remaining 16 eyes (unstable group),
      7 of which had significant evidence of abnormal topography. Statistical analysis
      showed no significant differences between two groups regarding age, sex, duration
      of contact lens wear, and refractive and topographic measures. The mean central
      corneal thickness on the final visit was significantly different between two
      groups (P<0.05). CONCLUSION: Contact lens induced corneal warpage may occur in a
      considerable proportion of soft contact lens wearers. A 2-week contact lens free
      period seems to be adequate for the cornea to stabilize; however, one cannot
      predict the minimum time needed for each individual patient. Repeating
      examinations to document corneal stability before refractive surgery may be a
      safer alternative.

PMID- 18343185
TI  - A new pentanuclear cyano-bridged complex [(Fe(II)(tetraazamacrocycle))3{mu-NC
      FeIII(CN)5)2]: synthesis, spectroscopic and magnetic characterization.
AB  - Hexacyanoferrate(III) reacts with [FeII(meso)(CH3CN)2](ClO4)2.2CH3CN
      (meso=5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane) in
      acetonitrile/water mixture producing the title complex, where three [Fe(meso)]2+
      units are connected by two [Fe(CN)6](3-) anions. Molecular modeling (MM+) shows a
      fairly linear molecule and Mossbauer data are consistent with two terminal
      pentacoordinated low spin iron(II)-meso units linked to one hexacoordinated low
      spin iron(II)-meso through two hexacoordinated low spin iron(III) units.
      Spectroscopic characterization showed a typical mixed-valence charge transfer
      band and the degree of electron coupling was calculated to be H(AB)=678 cm(-1).
      Magnetic properties exhibited an antiferromagnetic exchange interaction between
      the iron(III) ions with a coupling constant J= -44 cm(-1).

PMID- 18343186
TI  - Spectrophotometric and conductometric study of complexation of salophen and some
      transition metal ions in nonaqueous polar solvents.
AB  - The complexation reaction between Cu2+, Co2+ and Ni2+ metal cations with N,N'
      bis(salicylidene)-1,2-phenylenediamine (salophen), in three nonaqueous polar
      solvents such as: acetonitrile (AN), dimethyl sulfoxide (DMSO), methanol (MeOH)
      and two binary mixtures of AN:DMSO and AN:MeOH at 25 degrees C were studied by
      spectrophotometric and conductometric methods. All investigated metal ions form
      1:1 ML complex which their stability constants were determined and increase as
      Irving-Williams stability order of Co2+ < Ni2+ < Cu2+ in all solvent systems
      except in the pure MeOH and binary mixture of AN:MeOH 20:80; in which, Ni2+ <
      Co2+ < Cu2+ was observed. The values of the thermodynamic parameters (DeltaH
      degrees , DeltaS degrees and DeltaG degrees ) for complexation reactions obtained
      from the temperature dependence of the stability constants and the results show
      that for all metal ion complexes, the value of DeltaH degrees , DeltaS degrees
      and DeltaG degrees are solvent dependent.

PMID- 18343187
TI  - Flow-injection chemiluminescence determination of chrysin and baicalein assisted
      by theoretical prediction of chemiluminescence behavior of chrysin and baicalein.
AB  - In this paper, the molecular connectivity indices were applied to theoretically
      predict the direct chemiluminescence (CL) behavior of chrysin and baicalein with
      our recently proposed discriminant function. Then, combined with flow-injection
      analysis, a new CL system for determination of chrysin and baicalein was
      proposed. The method was based on the oxidation of chrysin and baicalein by
      acidic KMnO(4) in the presence of formaldehyde to produce strong CL emission. The
      present paper suggested a new model to discover new CL analytical system: first,
      to theoretical predict the CL behavior, and the second, to suggest analytical
      system.

PMID- 18343188
TI  - Synthesis and characterization of new nano-particles as blue ceramic pigment.
AB  - The synthesis of a new nano-blue ceramic pigment CoxMg1-xAl2O4 (0 < or = x < or =
      0.1) using the combination between co-precipitation and combustion synthesis (CS)
      method. The structure of pigments is assigned based on thermogravimetric and
      differential thermogravimetric analysis (TG-DTGA), X-ray diffractions (XRD), and
      UV-vis spectroscopy. Also, diffuse reflectance spectroscopy (DRS) using CIE
      L*a*b* parameter measurement method, infrared spectroscopy (IR) and transmission
      electron microscopy (TEM) is used. The result revealed that the nano-size
      particle pigment was obtained in range 24-35 nm by using 3-methyl-pyrozole-5-one
      (3MP5O) as a fuel at 400 degrees C in open furnace. Also, results show the
      varying colors and particles' size as a result of different calcination
      temperatures from 500 to 1200 degrees C for 2h.

PMID- 18343189
TI  - Solvent effects on the infrared spectra of beta-alkoxyvinyl methyl ketones I.
      Carbonyl and vinyl stretching vibrations.
AB  - Infrared spectroscopy studies of six beta-alkoxyvinyl methyl ketones, with common
      structure R(1)O-CR(2)CH-COR(3), where R(1)=R(3)=CH(3), R(2)=H (1); R(1)=C(2)H(5),
      R(2)=H (2); R(3)=CF(3); R(1)=R(2)=CH(3), R(3)=CF(3) (3); R(1)=C(2)H(5),
      R(2)=C(6)H(5), R(3)=CF(3) (4); R(1)=C(2)H(5), R(2)=4-O(2)NC(6)H(4), R(3)=CF(3)
      (5); R(1)=C(2)H(5), R(2)=C(CH(3))(3), R(3)=CF(3) (6) in 11 pure organic solvents
      of different polarity were undertaken to investigate the solute-solvent
      interactions and to correlate solvent properties by means of linear solvation
      energy relationships (LSER) with the carbonyl and vinyl stretching vibrations of
      existing stereoisomeric forms. It was shown that contrary to simple carbonyl
      containing compounds where solvent HBD acidity (alpha) has the largest influence
      on the nu (CO) band shift to lower wavenumbers, the dipolarity/polarizability
      (pi) term plays the main role in the interactions of conjugated enones with
      solvent molecules leading to the nu (CO) and nu (CC) bathochromic band shifts.
      The trifluoroacetyl group possesses a reduced ability to form hydrogen bonds with
      solvents. For the nu (CC) band of non-fluorinated enone 1 solvent HBD acidity
      (alpha) and solvent HBA basicity term (beta) play a perceptible role, whereas for
      2 these terms are not significant. beta-Substituents in fluorinated enones such
      as R(2)=H, C(6)H(5), and C(CH(3))(3) assist in the intermolecular hydrogen bond
      formation of the carbonyl moiety with HBD solvents, while beta-substituents such
      as CH(3) and 4-NO(2)C(6)H(4) prevent the CO group to form the H-bonds with HBD
      solvents (the solvent HBD acidity term (alpha) is not significant). The
      comparison of four conformers of the enone 1 reveals that (EEE) form is the most
      polarizable conformer; the influences of the solvent dipolarity/polarizability
      (pi) and solvent HBD acidity (alpha) term on the bathochromic nu (CO) band shift
      are opposite to one another.

PMID- 18343190
TI  - Structural and spectral studies of palladium(II) and platinum(II) complexes
      derived from N,N,N,N-tetradentate macrocyclic ligands.
AB  - Palladium(II) and platinum(II) complexes having the general composition [M(L)] X2
      (where M=Pd(II) and Pt(II), L=3,4,12,13-tetraphenyl-2,5,11,14,19,20-hexaaza
      tricyclo [13.3.1.1.(6-10)] cosa-1(19), 2,4,6,8,10,(20),11,13,15,17-decaene (L1);
      3,4,13,14-tetraphenyl-2,5,12,15-tetraaza tricyclo [11,0,0,(6-11)] cosa
      1(16),2,4,7,9,6(11),12,14,17, 19-decaene (L2); 2,3,8,9-tetraphenyl-1,4,7,10
      tetraaza cyclododeca-1,3,7,9-tetraene (L3) and X=Cl(-)) have been synthesized.
      The ligands were characterized on the basis of elemental analyses, IR, 1H NMR and
      EI mass spectral studies while that of the complexes were characterized on the
      basis of elemental analyses, molar conductance measurements, magnetic
      susceptibility measurements, IR, and electronic spectral techniques. All the
      complexes were found to be diamagnetic. The structures consist of monomeric units
      in which the Pd(II) and Pt(II) atoms exhibit square planar geometry.

PMID- 18343191
TI  - EPR study of Cu(2+)-doped tetraaqua-di(nicotinamide)Co(II) saccharinate single
      crystals.
AB  - The electron paramagnetic resonance spectra of Cu(2+) impurities in
      [Co(nicotinamide)(2)(H(2)O)(4)](saccharinate)(2) single crystals have been
      studied at ambient temperature in three mutually perpendicular planes. The
      angular variation of the spectra shows that the Cu(2+) ion substitutes the Co(2+)
      site in the lattice. The EPR spectra of Cu(2+) ions are characteristic of
      tetragonally elongated octahedral site. The spin-Hamiltonien parameters were
      obtained from the single crystal EPR analysis. The ground-state wave function of
      Cu(2+) ion in the lattice has been constructed.

PMID- 18343192
TI  - Spectroscopic and structural elucidation of 4-dimethylaminopyridine and its
      hydrogensquarate.
AB  - A distortion of the aromatic character and stabilization of the imino-form as a
      result of the protonation of 4-dimethylaminopyridine was established by IR-, UV-
      and 1H NMR-spectral analysis of 4-diaminopyridinium hydrogensquarate. Quantum
      chemical calculations were carried out at MP2 and B3LYP levels of theory and a 6
      311++G** basis set with a view to determining the changes in geometrical
      parameters and IR-spectroscopic characteristics resulting from Npy protonation.
      Linear-dichroic IR-spectroscopy coupled with the orientation techniques of solid
      samples as liquid crystal suspensions and melted solid polycrystalline films was
      applied for the identification of the IR-bands, characteristic for the structural
      fragments of the neutral and imino-form of the pyridine derivative. The spectral
      results were compared with the structure, obtained by a single crystal X-ray
      analysis. The salt contains dimmers of hydrogensquarate anions and Npy protonated
      cations of which the former are stabilized by strong intermolecular OH...O
      interactions (2.552 angstroms and 143.1(2) degrees). The 4-diaminopyridinium
      cation interacts with the anion through moderate NH...O bonds (2.729 angstroms
      and 165.0(0) degrees ). Individual cations are pi-pi stacked with their neighbors
      at a distance of 3.406 angstroms.

PMID- 18343193
TI  - Frequency of detection of respiratory viruses in the lower respiratory tract of
      hospitalized adults.
AB  - BACKGROUND: Respiratory infections are the most common infections in humans. The
      prevalence of respiratory viruses in adults is largely underestimated, and
      relevant data mostly concern infants and children. OBJECTIVES: To evaluate the
      prevalence of respiratory viruses in adults hospitalized in Italy. STUDY DESIGN:
      During April 2004--May 2005, 510 consecutive lower respiratory tract samples were
      prospectively collected. These were evaluated with a molecular panel that
      detected 12 respiratory viruses. RESULTS: Two hundred and fifteen samples were
      positive for at least one viral pathogen, with an overall sample prevalence of
      42.2%. Human rhinoviruses (HRVs) were the most commonly detected viruses (32.9%),
      followed by influenza virus (FLU)-A (9.0%); the other viruses were 2% or less.
      Multiple agents were detected in 30 samples from 29 patients, resulting in a co
      infection rate of 6.7%. CONCLUSIONS: This study shows a high prevalence of
      viruses in the lower respiratory tract samples of hospitalized adults, mostly HRV
      and FLU-A. It is not possible to establish the role of viruses detected at low
      frequency, but our findings suggest the necessity to consider them as potential
      causes or precursors of lower respiratory tract infections (LRTIs).

PMID- 18343194
TI  - HHV-8 linked to Kaposi's sarcoma, Castleman's disease and primary effusion
      lymphoma in a HIV-1-infected man.

PMID- 18343195
TI  - Difficult memory task during postural tasks of various difficulties in young and
      older people: a pilot study.
AB  - OBJECTIVE: This study examined the effects of a difficult and individually
      tailored additional cognitive task on postural stability and electromyographic
      (EMG) activities of the ankle dorsi- and plantar-flexors, in young and older
      individuals performing postural tasks of varying difficulties. METHODS: Eight
      young (mean age=24 years) and eight older (74 years) men took part in the
      investigation. Centre of pressure velocity and surface EMG of ankle joint muscles
      were both examined during various postural conditions. RESULTS: The main findings
      suggested that high levels of muscle activity were a characteristic of age
      related declines in postural stability. Moreover, during the complex posture, the
      postural instability, as well as the EMG activity of the ankle joint muscles, was
      decreased in older adults when the difficult memory task was added. Regarding
      young participants, the performance in the cognitive task was significantly
      improved during the complex posture compared to the easy one. CONCLUSIONS: These
      findings showed that the execution of a second task would make it possible to
      improve the performance in the original task. SIGNIFICANCE: This pilot study
      seemed to show that, depending on age, the task of highest priority would be the
      cognitive one for young adults and the postural one for older people.

PMID- 18343196
TI  - Tissue kallikrein deficiency aggravates cardiac remodelling and decreases
      survival after myocardial infarction in mice.
AB  - BACKGROUND: Tissue kallikrein (TK) is a major kinin-releasing enzyme present in
      arteries. TK is involved in cardioprotection in the setting of acute myocardial
      ischaemia but its role in post-ischaemic heart failure (HF), a major cause of
      delayed mortality after myocardial infarction (MI), is unknown. AIM: To determine
      whether TK deficiency in the mouse influences survival and cardiac remodelling
      after MI. METHODS: MI was induced in 10 week-old male TK-deficient mice and wild
      type littermates. Survival was assessed up to 14 months. Cardiac morphological
      and functional parameters were serially measured by echocardiography. In another
      experiment, myocardial capillary density and NOS content were evaluated at 3
      months. RESULTS: Infarct size was similar in both genotypes. MI resulted in
      severe cardiac dysfunction. Up to 12 months after MI, TK(-/-) mice displayed an
      increased mortality rate (P<0.05, relative risk of death=3.41) and aggravation of
      left ventricular hypertrophy and dilatation by comparison with TK(+/+) (+18% and
      +27% respectively, both P<0.05). NOS1 and NOS3 were abnormally regulated in the
      heart of TK(-/-) mice after MI. CONCLUSIONS: TK exerts a protective role in HF in
      mice. Coronary effects are probably involved. As partial genetic deficiency in TK
      activity occurs in humans, TK-deficient subjects may be at increased risk of
      mortality in HF.

PMID- 18343197
TI  - Health-related quality of life during adjuvant treatment for breast cancer among
      postmenopausal women.
AB  - The purpose of the present study was twofold: first, to describe changes of
      Health-Related Quality of Life (HRQoL) during the adjuvant treatment among
      postmenopausal women with breast cancer; second, in the same population to
      identify the best predictors of Overall Quality of Life (QoL) after treatment,
      from perceived functioning, symptoms, emotional distress and clinical/demographic
      variables measured at baseline. The study group was 150 women (> or = 55 years of
      age) scheduled for adjuvant chemotherapy (CT, n=75) or radiotherapy (RT, n=75).
      They were examined before (baseline), during and after completing the treatment.
      Data about QoL, perceived functioning, symptoms and emotional distress were
      collected with the European Organisation for Research and Treatment of Cancer
      (EORTC)-QLQ-C30, BR23 and Hospital Anxiety and Depression Scale (HADS)
      questionnaires. The general finding was that the adjuvant treatments were
      associated with decrease in overall QoL, physical and role functioning, anxiety
      and body image, as well as with increase in fatigue, dyspnoea, pain,
      nausea/vomiting, constipation and systemic therapy side effects measured over
      time. For women receiving CT, better emotional functioning and less pain at
      baseline predicted better overall QoL at the end of the treatment. For women
      receiving RT, better physical and emotional functioning, less breast symptoms and
      lower tumour stage at baseline predicted better overall QoL at the end of the
      treatment.

PMID- 18343198
TI  - Nuclear receptors: doubling up in the lung.
AB  - Inhaled corticosteroids are highly effective in the treatment of asthma and also
      show efficacy in chronic obstructive pulmonary disease (COPD). Considerable
      effort continues to be focused on improvement of their pharmacology and
      pharmacokinetic properties. Corticosteroids act through the glucocorticoid
      receptor, one of a family of ligand activated transcription factors. These
      proteins are highly tractable to drug discovery, and are targeted by a number of
      existing therapeutic agents. The possibility that family members other than the
      glucocorticoid receptor might have therapeutic benefit in lung disease has
      received increasing attention. Recent studies using ligands for the vitamin D3
      receptor, the peroxisome proliferator-activated receptors, and the liver X
      receptor have demonstrated significant potential for these novel targets in the
      treatment of lung disease.

PMID- 18343199
TI  - Potential donor segregation to promote blood donation.
AB  - This work is set in the field of social marketing and more specifically in the
      context of blood donation. Its principal objective focuses on segregating
      potential donors by using the inhibitors or barriers to a blood donation
      behaviour as criteria. Moreover, an analysis of the predisposition to donate
      blood, the intrinsic and extrinsic motivations for donating blood, and the
      incentives that may stimulate their donation conduct was conducted for each of
      the four identified groups. The results reveal that the four segments differ
      significantly in their predisposition to donate, in their motivations and in the
      incentives that encourage them to donate blood.

PMID- 18343200
TI  - Acceptance and Commitment Therapy and yoga for drug-refractory epilepsy: a
      randomized controlled trial.
AB  - OBJECTIVE: There is a need for controlled outcome studies on behavioral treatment
      of epilepsy. The purpose of this study was to evaluate Acceptance and Commitment
      Therapy (ACT) and yoga in the treatment of epilepsy. METHODS: The design
      consisted of a randomized controlled trial with repeated measures (N=18). All
      participants had an EEG-verified epilepsy diagnosis with drug-refractory
      seizures. Participants were randomized into one of two groups: ACT or yoga.
      Therapeutic effects were measured using seizure index (frequency x duration) and
      quality of life (Satisfaction with Life Scale, WHOQOL-BREF). The treatment
      protocols consisted of 12 hours of professional therapy distributed in two
      individual sessions, two group sessions during a 5-week period, and booster
      sessions at 6 and 12 months posttreatment. Seizure index was continuously
      assessed during the 3-month baseline and 12-month follow-up. Quality of life was
      measured after treatment and at the 6-month and 1-year follow-ups. RESULTS: The
      results indicate that both ACT and yoga significantly reduce seizure index and
      increase quality of life over time. ACT reduced seizure index significantly more
      as compared with yoga. Participants in both the ACT and yoga groups improved
      their quality of life significantly as measured by one of two quality-of-life
      instruments. The ACT group increased their quality of life significantly as
      compared with the yoga group as measured by the WHOQOL-BREF, and the yoga group
      increased their quality of life significantly as compared with the ACT group as
      measured by the SWLS. CONCLUSIONS: The results of this study suggest that
      complementary treatments, such as ACT and yoga, decrease seizure index and
      increase quality of life.

PMID- 18343201
TI  - The use of self-generation procedures facilitates verbal memory in individuals
      with seizure disorders.
AB  - The efficacy of a self-generation encoding procedure in facilitating the encoding
      and retrieval of verbal memories was compared with the didactic presentation of
      information in individuals with seizure disorders. Through a within-subject
      design, 87 patients (25 left temporal seizure onset, 29 right temporal, 8
      frontal, and 25 psychogenic nonepileptic seizures) received a self-generation
      learning condition and a didactic learning condition and were subsequently tested
      for verbal paired associate free recall, cued recall, and recognition memory. All
      patient groups benefited from the use of the self-generation condition relative
      to the didactic condition. Better performance occurred with the self-generation
      procedure for cued recall and recognition memory test performance, but not free
      recall. Individuals with a left temporal seizure onset (patients with the poorest
      memory performance on the didactic condition) benefited the most from the self
      generation condition. A memory encoding strategy that actively involves patient
      participation enhances memory performance.

PMID- 18343202
TI  - Expression of MEGAP mRNA during embryonic development.
AB  - Mental retardation (MR) affects up to two percent of the population and is
      usually accompanied by impaired learning and memory. MR is frequently associated
      with mutations of genes involved in Rho signal transduction cascades. Rho signal
      transduction pathways regulate axonal and dendritic growth during embryonic
      development and morphological adaptations of dendritic spines during synaptic
      plasticity in adult neurons. The MEGAP/SRGAP3 protein is part of the Rho signal
      transduction cascades. Mutation of MEGAP (Mental disorder associated GTPase
      activating protein) gene is present in some patients who have MR, ataxia and
      monosomy for the distal portion of the short arm of chromosome 3. Here, we
      investigated the pattern of mouse MEGAP mRNA expression during embryonic
      development. Mouse embryos and brain sections from stage E10 to adults were
      analysed by in-situ hybridisation for MEGAP transcript in whole-mount and in
      brain sections. We demonstrate here robust expression of MEGAP mRNA in the whole
      central nervous system of E10 embryos. At E12, we also detected MEGAP in dorsal
      root ganglia. This pattern narrows in adult animals into an expression mainly in
      hippocampus and cortex. Our findings support the presumed role of MEGAP in Rho
      associated MR.

PMID- 18343203
TI  - Aging and hormones of the hypothalamo-pituitary axis: gonadotropic axis in men
      and somatotropic axes in men and women.
AB  - Neuroendocrinology of the aging (male) gonadal and (male and female) somatotropic
      axes will be reviewed. A companion chapter discusses reproductive hormonal
      changes in aging women. Both the gonadal and growth-hormone/insulin-like growth
      factor (GH/IGF-I) axes function as ensembles. The ensembles comprise tripartite
      interactions among the brain (hypothalamus), anterior pituitary gland
      (gonadotrope and somatotrope cells) and target organs (testis, liver, muscle, fat
      and brain). Compelling evidence indicates that combined hypothalamic and gonadal
      adaptations operate in the reproductive axis of older men, and multiple
      hypothalamic adaptations prevail in the GH axis of elderly men and women.
      Evolving investigative methods allow more precise parsing of the particular
      mechanisms that subserve such age-related changes, and suggest novel
      interventional strategies to evaluate the physiological impact of the dynamic
      alterations discerned in aging individuals.

PMID- 18343205
TI  - Direct involvement of the tumor suppressor p53 in nucleotide excision repair.
AB  - The tumor suppressor p53 enhances repair of UVC-induced DNA damage. The comet-NE
      assay, a conventional alkaline comet assay which includes a nuclear digestion
      step, was used to examine the effects of p53 on the excision activity of nuclear
      extracts (NEs). In contrast with untreated NEs, NEs immunodepleted of p53 or NEs
      of p53-null cells were unable to excise UVC-induced DNA adducts. Introduction of
      p53 by transfection restored the excision activity to NEs of p53-null cells.
      Deletion of the N-terminal 99 amino acids and/or the C-terminal 85 amino acids of
      p53 barely affected the excision activity, whereas further deletion of the C
      terminus of p53 by another 10 amino acids completely abolished the excision
      activity of NEs. Immunostaining following localized UV irradiation was used to
      examine the effects of p53 on the recruitment of repair proteins for nucleotide
      excision repair (NER). Although recruitment of XPC occurred regardless of the
      presence of p53, the recruitment of XPB was p53-dependent. However, p53 with the
      95 amino acid deletion at its C-terminus was unable to support this recruitment
      of XPB. Consistently, intact p53 (but not the C-terminal 95 residue truncated
      version) was detected in co-immunoprecipitation assays with an anti-XPB antibody.
      These results support the hypothesis that p53 facilitates NER through direct
      involvement by protein-protein interactions.

PMID- 18343204
TI  - DNA repair gets physical: mapping an XPA-binding site on ERCC1.
AB  - Two recent reports provide new physical information on how the XPA protein
      recruits the ERCC1-XPF heterodimer to the site of damage during the process of
      mammalian nucleotide excision repair (NER). Using chemical shift perturbation NMR
      experiments, the contact sites between a central fragment of ERCC1 and an XPA
      fragment have been mapped. While both studies agree with regard to the XPA
      binding site, they differ on whether the ERCC1-XPA complex can simultaneously
      bind DNA. These studies have important implications for both the molecular
      process and the design of potential inhibitors of NER.

PMID- 18343206
TI  - Determination of toxaphene specific congeners in fish liver oil and feedingstuff
      using gas chromatography coupled to high resolution mass spectrometry.
AB  - A new method for the determination of nine toxaphene specific congeners in fish
      liver oil and feedingstuff has been developed. The samples were extracted using
      pressurized liquid extraction followed by a purification on silica and florisil
      columns. Identification and quantification were conducted using GC-(EI)-HRMS, and
      comparison with MS/MS detection was performed, using electron ionization and
      negative chemical ionization. Limits of detection were ranged from 0.01 to 0.22
      microg kg(-1) (12% moisture) as required for feed samples. The calibration curves
      showed a good linearity for all congeners (R(2)>0.99). Repeatability was below 9%
      for all the congeners and recoveries were in-between 73 and 86%. This analytical
      method was applied to the quantification of thirteen real samples collected
      within national monitoring plans for further risk assessment.

PMID- 18343207
TI  - Size-exclusion chromatography with evaporative light scattering detection: Method
      for determination of polydimethylsiloxanes. I. Testing dependence of molecular
      weight of polydimethylsiloxanes and injected mass upon the detector signal.
AB  - In recent years the evaporative light scattering detector has become a promising
      device in the analysis of variable chemical compounds using liquid
      chromatography. Due to the detection specificity, based on the scattering of the
      laser light on non-volatile analyte particles, this detector is considered a most
      universal one. Many authors consider detector signal as a mass signal and
      subsequently, evaporative light scattering detector has been regarded as a mass
      detector. Although the scientists pinpoint to many advantages of this device,
      many of its drawbacks were also noticed. Due to variable examinations carried out
      some scientist characterised the detector response as a non-linear, seeing in
      fact a significant limitation of this detector for the purposes of quantitative
      tests. The author of the present study researched, in many ways, for the solution
      to this problem, by carrying out tests on polydimethylsiloxanes (PDMS) of a
      linear structure. The aim of this study was to test the dependence of the
      evaporative light scattering detector signal upon the molecular weight of PDMS of
      a linear structure and viscosity ranging from 10 to 60,000 cSt and the injected
      mass. The evaluation of function monotonicity of the detector response and
      determination of the function for particular analytes referred to the mass ranges
      of 8.9-149.0 microg. In order to find the dependence of the integrated signal
      value of the detector signal intensity, expressed as a surface area in mug, upon
      analyte mass for particular PDMS, several analytical functions and formulas were
      used. Parameters of regression equations were calculated for linear and non
      linear functions as well as their logarithmic transformations. The aim of the
      research for the optimal regression equation could mean increased reliability of
      results obtained from analyses of PDMS.

PMID- 18343208
TI  - Quantification methods of folpet degradation products in plasma with HPLC-UV/DAD:
      application to an in vivo toxicokinetic study in rats.
AB  - Solid-phase extractions followed by HPLC-UV/DAD methods were developed for
      occupational biological monitoring or forensic investigations of the fungicide
      folpet using its degradation products, phthalimide and phthalamic acid as plasma
      biomarkers. These methods show good linearity (r>0.9955), precision (CV<15%) and
      accuracy (bias<14.8%). The lower limits of quantification for phthalimide and
      phthalamic acid were 10 and 20 ng/ml and the absolute recoveries were higher than
      86% and 68%, respectively. Applying these methods, a plasma toxicokinetic study
      of folpet in rats after intratracheal administration of Folpan 80WG showed that
      inhalation of folpet could be a route of exposure with an important systemic
      absorption.

PMID- 18343209
TI  - Prenatal diagnosis of propionic acidemia by measuring methylcitric acid in dried
      amniotic fluid on filter paper using GC/MS.
AB  - Propionic acidemia is a frequent inborn error of metabolism. Methylcitric acid, a
      key indicator of propionic acidemia, increases in the amniotic fluid of affected
      fetuses. For prenatal diagnosis, the methylcitric acid in amniotic fluid can be
      measured by stable-isotope dilution GC/MS. Here, we quantified this indicator in
      samples of amniotic fluid that had been dried on filter paper and transported at
      ambient temperatures, and compared the results with data obtained from the
      original amniotic fluid. We then used the filter-paper method to screen at-risk
      fetuses and obtained a clear-cut diagnosis in each case.

PMID- 18343210
TI  - Tracheostomy with thyroidectomy: indications, management and outcome: a
      prospective study.
AB  - OBJECTIVES: This study aims to determine the indications, course and outcome of
      pre-operative and post-thyroidectomy tracheostomy. SUBJECTS AND METHODS: This is
      a prospective descriptive study conducted in Khartoum Teaching Hospital in the
      period between March 2000 and March 2005. Fifty-nine patients had tracheostomy
      out of 964 thyroidectomy patients, giving an incidence of 6%. RESULTS: The
      decision of doing tracheostomy was taken intra-operatively in 41 patients (69%),
      all presenting with strider. In 25 of those 41 patients there was intra-operative
      tracheal deformity with narrowing (>50% of tracheal circumference on radiology)
      and gland adherence to the tracheal wall; the remaining 16 patients had
      tracheomalacia. Of those 41 patients, 25 presented with severe strider and needed
      urgent surgery (5 with recurrent anaplastic carcinoma, 5 with intrathoracic
      goitres that necessitated median sternotomy and 15 with huge goitres (of whom 7
      were recurrent goitres). In the remaining 18 patients (31%) emergency post
      operative tracheostomy was done following endotracheal extubation up to 48 h post
      operatively. There were 2 deaths (3.4%); one patient died due to tracheostomy
      care and the other from myocardial infarction. CONCLUSION: Tracheostomy is a safe
      procedure and gives a good alternative to delayed endotracheal extubation in post
      thyroidectomy patients expected to have respiratory failure in places where post
      operative anaesthetic care is lacking.

PMID- 18343211
TI  - Endovascular aneurysm repair (EVAR).
AB  - Endovascular repair of an abdominal aortic aneurysm (AAA) is an evolving
      technology which continues to be practiced in more and more centres worldwide in
      an effort to avoid major abdominal surgery and its associated morbidity and
      mortality. As with conventional open surgery, the objective of endovascular
      management is to provide a durable repair maintaining antegrade flow in the graft
      whilst simultaneously excluding flow in the aneurysm. Endovascular treatment
      offers a less invasive alternative to standard surgical repair with the potential
      of reduced hospitalisation, morbidity and mortality.

PMID- 18343212
TI  - Structural elucidation of 4'-epiadriamycin by nuclear magnetic resonance
      spectroscopy and comparison with adriamycin and daunomycin using quantum
      mechanical and restrained molecular dynamics approach.
AB  - The structural and electronic properties of 4'-epiadriamycin, adriamycin, and
      daunomycin have been studied using density functional theory (DFT) employing
      B3LYP exchange correlation. The chemical shifts of (1)H and (13)C resonances in
      nuclear magnetic resonance spectra have been calculated using Gauge-Invariant
      Atomic Orbital (GIAO) method as implemented in Gaussian 98 and compared with
      experimental spectra recorded at 500 MHz. (13)C resonances of drugs have been
      assigned for the first time. A restrained molecular dynamics approach was used to
      get the optimized solution structure of drugs using inter-proton distance
      constraints obtained from 2D NOESY spectra. The glycosidic angle C7-O7-C1'-C2' is
      found to show considerable flexibility by adopting 156 degrees -161 degrees (I),
      142 degrees -143 degrees (II), and 38 degrees -78 degrees (III) conformations, of
      which the biological relevant structure appears to be the conformer II. The
      observed different conformations of the three drugs are correlated to the
      differential anticancer activity and the available biochemical evidence exhibited
      by these drugs.

PMID- 18343213
TI  - Glyoxal causes inflammatory injury in human vascular endothelial cells.
AB  - To explore mechanisms of diabetes-associated vascular endothelial cells (ECs)
      injury, human umbilical vein ECs were treated for 24h with high glucose (HG;
      26mM), advanced glycation end-products (AGEs; 100mug/ml) or their intermediate,
      glyoxal (GO: 50-5000muM). HG and AGEs had no effects on ECs morphology and
      inflammatory states as measured by vascular cell adhesion molecule (VCAM)-1 and
      cyclooxygenase (COX)-2 expressions. GO (500muM, 24h) induced cytotoxic
      morphological changes and protein expression of COX-2 but not VCAM-1. GO (500muM,
      24h) activated ERK but not JNK, p38 or NF-kappaB. However, ERK inhibitor PD98059
      was ineffective to GO-induced COX-2. While EUK134, synthetic combined superoxide
      dismutase/catalase mimetic, had no effect on GO-mediated inflammation, sodium
      nitroprusside inhibited it. The present results indicate that glyoxal, a
      metabolite of glucose might be a more powerful inducer for vascular ECs
      inflammatory injury. Nitric oxide but not anti-oxidant is preventive against GO
      mediated inflammatory injury.

PMID- 18343214
TI  - Identification of Glypican3 as a novel GLUT4-binding protein.
AB  - Insulin stimulates glucose uptake in fat and muscle primarily by stimulating the
      translocation of vesicles containing facilitative glucose transporters, GLUT4,
      from intracellular compartments to the plasma membrane. Although cell surface
      externalization of GLUT4 is critical for glucose transport, the mechanism
      regulating cell surface GLUT4 remains unknown. Using a yeast two-hybrid screening
      system, we have screened GLUT4-binding proteins, and identified a novel glycosyl
      phosphatidyl inositol (GPI)-linked proteoglycan, Glypican3 (GPC3). We confirmed
      their interaction using immunoprecipitation and a GST pull-down assay. We also
      revealed that GPC3 and GLUT4 to co-localized at the plasma membrane, using
      immunofluorescent microscopy. Furthermore, we observed that glucose uptake in
      GPC3-overexpressing adipocytes was increased by 30% as compared to control cells.
      These findings suggest that GPC3 may play roles in glucose transport through
      GLUT4.

PMID- 18343215
TI  - The ABCA1 Q597R mutant undergoes trafficking from the ER upon ER stress.
AB  - Mutations in ATP binding cassette transporter 1 (ABCA1), a membrane protein
      associated with cellular cholesterol efflux, cause Tangier disease (TD).
      Previously, we showed that an ABCA1 Q597R mutant (QR) identified in TD is
      retained in the endoplasmic reticulum. Here, we report that QR trafficking to the
      plasma membrane was rapidly induced by thapsigargin or DTT, indicating that ER
      stress-induced QR trafficking. However, pharmacological rescue of ABCA1 activity
      was not observed. The trafficking was dependent on COPII components and occurred
      via the ER-Golgi intermediate compartments. Furthermore, we found that QR was
      more sensitive to ER stress than ATF6, a transcription factor associated with the
      ER stress response. These results suggest that thapsigargin can be effective in
      correcting trafficking defects, and raise the possibility that ER stress-induced
      trafficking is involved in ER quality control.

PMID- 18343216
TI  - BRCA1 regulates caveolin-1 expression and inhibits cell invasiveness.
AB  - BRCA1 is involved in multiple biological processes including DNA damage repair,
      cell growth, apoptosis, and transcriptional activation. Also, BRCA1 plays key
      roles in inhibiting cancer progression. Caveolin-1 is identified as a tumor
      suppressor and regulates the invasiveness of cells. However, the interactions
      between BRCA1 and caveolin-1 remain largely unknown. We have investigated the
      potential function of BRCA1 in regulation of caveolin-1 gene expression and its
      subcellular localization as well. The observations from RT-PCR, transfection,
      RNAi, and luciferase assays implied that BRCA1 could elevate caveolin-1 mRNA
      levels via transactivation of the caveolin-1 promoter region. Additionally,
      immunofluorescent approach showed that BRCA1 might inhibit the invasiveness and
      metastatic abilities of mammalian cells by inducing the redistribution of
      caveolin-1 from the cytoplasm to the cell membrane.

PMID- 18343217
TI  - Ectopic expression of eIF4E-transporter triggers the movement of eIF4E into P
      bodies, inhibiting steady-state translation but not the pioneer round of
      translation.
AB  - Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance
      mechanism; this process removes faulty mRNAs harboring premature termination
      codons (PTCs). NMD targets newly synthesized mRNAs bound by nuclear cap-binding
      proteins 80/20 (CBP80/20) and exon junction complex (EJC), the former of which is
      thought to recruit the ribosome to initiate the pioneer round of translation.
      After completion of the pioneer round of translation, CBP80/20 is replaced by the
      cytoplasmic cap-binding protein eIF4E, which mediates steady-state translation in
      the cytoplasm. Here, we show that overexpression of eIF4E-T preferentially
      inhibits cap-dependent steady-state translation, but not the pioneer round of
      translation. We also demonstrate that overexpression of eIF4E-T or Dcp1a triggers
      the movement of eIF4E into the processing bodies. These results suggest that the
      pioneer round of translation differs from steady-state translation in terms of
      ribosome recruitment.

PMID- 18343218
TI  - Induction of expression and co-localization of heat shock polypeptides with the
      polyalanine expansion mutant of poly(A)-binding protein N1 after chemical stress.
AB  - Formation of nuclear inclusions consisting of aggregates of a polyalanine
      expansion mutant of nuclear poly(A)-binding protein (PABPN1) is the hallmark of
      oculopharyngeal muscular dystrophy (OPMD). OPMD is a late onset autosomal
      dominant disease. Patients with this disorder exhibit progressive swallowing
      difficulty and drooping of their eye lids, which starts around the age of 50.
      Previously we have shown that treatment of cells expressing the mutant PABPN1
      with a number of chemicals such as ibuprofen, indomethacin, ZnSO(4), and 8
      hydroxy-quinoline induces HSP70 expression and reduces PABPN1 aggregation. In
      these studies we have shown that expression of additional HSPs including HSP27,
      HSP40, and HSP105 were induced in mutant PABPN1 expressing cells following
      exposure to the chemicals mentioned above. Furthermore, all three additional HSPs
      were translocated to the nucleus and probably helped to properly fold the mutant
      PABPN1 by co-localizing with this protein.

PMID- 18343219
TI  - Thr but Asn of the N-glycosylation sites of PrP is indispensable for its
      misfolding.
AB  - Prion protein (PrP) contains two N-linked glycosylation sites. It is unknown
      which amino acid substitution contributes most efficiently to the abolishment of
      N-linked glycosylations. To define the influence of amino acid substitution at
      the N-linked glycosylation sites on the conversion efficiency of mouse PrP, we
      tested each of all 19 amino acid substitutions at either one of the N-linked
      glycosylation sites (codon 180, 182, 196 or 198). The conversion efficiency of
      the mutagenized PrP was highly dependent on the newly introduced amino acid
      itself regardless of the absence of N-linked glycosylation in scrapie-infected
      mouse neuroblastoma cells. The majority of mutant PrP with substitutions at the
      Asn residues of the N-linked glycosylation sites were conversion-competent,
      whereas most mutant PrP with substitutions at the Thr residues were conversion
      incompetent. These findings emphasize that the Asn residues of the N-linked
      glycosylation sites are replaceable to abolish N-linked glycosylations without
      directly affecting the protein function.

PMID- 18343220
TI  - The extracellular matrix protein fibronectin is a substrate for kallikrein 7.
AB  - Kallikrein 7 (hK7), a chymostatin-like serine protease, is overexpressed in
      pancreatic adenocarcinomas as well as other human cancers. Although it has been
      demonstrated to participate in normal desquamation by facilitating cell shedding
      at the skin surface, its role in human malignancies remains unclear. To
      investigate the ability of hK7 to degrade components of the extracellular matrix
      (ECM), recombinant hK7 was expressed and purified from cultured mammalian cells.
      Using a three-step chromatographic purification procedure, recombinant hK7 was
      obtained that displayed robust proteolytic activity against a fluorogenic peptide
      substrate following activation by thermolysin. We demonstrate that the active
      protease is able to cleave fibronectin in a time-dependent manner, but not
      laminin, using an in vitro degradation assay. These findings indicate that the
      aberrant expression and secretion of hK7 in human tumors may facilitate
      metastasis by directly degrading components of the extracellular matrix and may
      thus play an important role in tumorigenesis.

PMID- 18343221
TI  - Activity-based selection of a proteolytic species using ribosome display.
AB  - We have examined the potential of displaying a protease species in vitro using
      ribosome display and demonstrate specific capture on the basis of its catalytic
      activity. Using a model bacterial cysteine protease, sortase A (SrtA), we show
      that this enzyme can be functionally expressed in vitro. By overlap PCR we
      constructed ribosome display templates with the SrtA open reading frame fused to
      a C terminal glycine-serine rich flexible linker and a tether derived from eGFP.
      Using the broad range cysteine protease irreversible inhibitor E-64 linked to
      acrylic beads, we show that we can isolate SrtA ribosome display ternary
      complexes, and recover their encoding mRNA by RT-PCR. This recovery was lost when
      applied to a SrtA catalytically inactive mutant, or could be alleviated by
      competition with free inhibitor. This sensitive technique could be further
      developed to allow the screening of proteases against putative inhibitors and/or
      the identification of novel proteolytic species.

PMID- 18343223
TI  - Anticancer properties of oxidation products of docosahexaenoic acid.
AB  - Docosahexaenoic acid (DHA) is the longest, most unsaturated, and hence, most
      oxidizable fatty acid commonly found in nature. The mechanisms behind DHA's many
      biological functions remain a subject of much debate. Here we review one
      important, but often unstudied, aspect of DHA function, namely, the potential
      role of its many oxidation products. We divide this review into camps, enzymatic
      and non-enzymatic oxidations, and report their effects primarily on induction of
      apoptosis in cancer cells. We conclude that the study of the effects of lipid
      peroxidation products on biochemical function will be a difficult but highly
      rewarding area for future studies.

PMID- 18343222
TI  - Docosahexaenoic acid (DHA) and hepatic gene transcription.
AB  - The type and quantity of dietary fat ingested contributes to the onset and
      progression of chronic diseases, like diabetes and atherosclerosis. The liver
      plays a central role in whole body lipid metabolism and responds rapidly to
      changes in dietary fat composition. Polyunsaturated fatty acids (PUFA) play a key
      role in membrane composition and function, metabolism and the control of gene
      expression. Certain PUFA, like the n-3 PUFA, enhance hepatic fatty acid oxidation
      and inhibit fatty acid synthesis and VLDL secretion, in part, by regulating gene
      expression. Our studies have established that key transcription factors, like
      PPARalpha, SREBP-1, ChREBP and MLX, are regulated by n-3 PUFA, which in turn
      control levels of proteins involved in lipid and carbohydrate metabolism. Of the
      n-3 PUFA, 22:6,n-3 has recently been established as a key controller of hepatic
      lipid synthesis. 22:6,n-3 controls the 26S proteasomal degradation of the nuclear
      form of SREBP-1. SREBP-1 is a major transcription factor that controls the
      expression of multiple genes involved fatty acid synthesis and desaturation.
      22:6,n-3 suppresses nuclear SREBP-1, which in turn suppresses lipogenesis. This
      mechanism is achieved, in part, through control of the phosphorylation status of
      protein kinases. This review will examine both the general features of PUFA
      regulated hepatic gene transcription and highlight the unique mechanisms by which
      22:6,n-3 impacts gene expression. The outcome of this analysis will reveal that
      changes in hepatic 22:6,n-3 content has a major impact on hepatic lipid and
      carbohydrate metabolism. Moreover, the mechanisms involve 22:6,n-3 control of
      several well-known signaling pathways, such as Akt, Erk1/2, Gsk3beta and PKC
      (novel or atypical). 22:6,n-3 control of these same signaling pathways in non
      hepatic tissues may help to explain the diverse actions of n-3 PUFA on such
      complex physiological processes as visual acuity and learning.

PMID- 18343224
TI  - Docosahexaenoic acid domains: the ultimate non-raft membrane domain.
AB  - What distinguishes polyunsaturated fatty acids (PUFAs) from less unsaturated
      fatty acids is the presence of a repeating =CH-CH(2)-CH= unit that produces an
      extremely flexible structure rapidly isomerizing through conformational states.
      Docosahexaenoic acid (DHA) with 6 double bonds is the most extreme example. The
      focus of this review is the profound impact that the high disorder of DHA has on
      its interaction with cholesterol when the PUFA is incorporated into membrane
      phospholipids. Results from a battery of biophysical techniques are described.
      They demonstrate an aversion of DHA for the sterol that drives the lateral
      segregation of DHA-containing phospholipids into liquid disordered (l(d)) domains
      that are depleted in cholesterol. These domains are compositionally and
      organizationally the antithesis of lipid rafts, the much-studied liquid ordered
      (l(o)) domain that is enriched in predominantly saturated sphingolipids and
      cholesterol. We hypothesize that the introduction of DHA-rich domains into the
      plasma membrane where they coexist with lipid rafts is the origin, in part, of
      the astonishing diversity of health benefits that accrue from dietary consumption
      of DHA. According to our model, changes in the conformation of signaling proteins
      when they move between these disparate domains have the potential to modulate
      cell function.

PMID- 18343225
TI  - Molecular basis of deletional hereditary persistence of fetal hemoglobin and
      deltabeta-thalassemia in Indian patients.

PMID- 18343226
TI  - Extracellular catalase activity protects cysteine cathepsins from inactivation by
      hydrogen peroxide.
AB  - The resistance of secreted cysteine cathepsins to peroxide inactivation was
      evaluated using as model THP-1 cells. Differentiated cells released mostly
      cathepsin B, but also cathepsins H, K, and L, with a maximum of endopeptidase
      activity at day 6. Addition of non-cytotoxic concentrations of H(2)O(2) did not
      affect mRNA expression levels and activity of cathepsins, while the catalase
      activity remained also unchanged, consistently with RT-PCR analysis. Conversely
      inhibition of extracellular catalase led to a striking inactivation of secreted
      cysteine cathepsins by H(2)O(2). This report suggests that catalase may
      participate in the protection of extracellular cysteine proteases against
      peroxidation.

PMID- 18343227
TI  - Clothing up DNA for all seasons: Histone chaperones and nucleosome assembly
      pathways.
AB  - In eukaryotes, the packaging of DNA into chromatin is essential for cell
      viability. Several important DNA metabolic events require the transient
      disruption of chromatin structure, but cells have evolved a number of elaborate
      pathways that operate throughout the cell cycle to prevent the deleterious
      effects of chromatin erosion. In this review, we describe a number of distinct
      nucleosome assembly pathways that function during DNA replication, transcription,
      cellular senescence and early embryogenesis. In addition, we illustrate some of
      the physiological consequences associated with defects in nucleosome assembly
      pathways.

PMID- 18343228
TI  - Antiparasitic compounds that target DNA.
AB  - Designed, synthetic heterocyclic diamidines have excellent activity against
      eukaryotic parasites that cause diseases such as sleeping sickness and leishmania
      and adversely affect millions of people each year. The most active compounds bind
      specifically and strongly in the DNA minor groove at AT sequences. The compounds
      enter parasite cells rapidly and appear first in the kinetoplast that contains
      the mitochondrial DNA of the parasite. With time the compounds are also generally
      seen in the cell nucleus but are not significantly observed in the cytoplasm. The
      kinetoplast decays over time and disappears from the mitochondria of treated
      cells. At this point the compounds begin to be observed in other regions of the
      cell, such as the acidocalcisomes. The cells typically die in 24-48h after
      treatment. Active compounds appear to selectively target extended AT sequences
      and induce changes in kinetoplast DNA minicircles that cause a synergistic
      destruction of the catenated kinetoplast DNA network and cell death.

PMID- 18343229
TI  - Identification of ETA and ETB binding domains using ET-derived photoprobes.
AB  - Using the structure of ET-1 as a template, a series of photosensitive analogs
      were developed to investigate the binding domain of ETA and ETB receptors.
      Accordingly, a p-benzoyl-l-phenylalanine (Bpa) residue was introduced into the
      peptide chain following a pattern aiming at scanning N- to C-terminal portions of
      the molecule. Among the analogs, those containing a Bpa amino acid in position 7
      ([L-Bpa7, Tyr(125I)13]hET-1) or 12 ([Nle7, L-Bpa12, Tyr(125I)13]hET-1) exhibited
      the capacity to activate both receptors, thus showing that residues Met-7 and Val
      12 of ET-1 do not play a key role in the activation process. The binding capacity
      of the probes was also evaluated on transfected CHO cells overexpressing either
      ETA or ETB receptors. Subsequently, these photoprobes were used to label ETA and
      ETB receptors overexpressed in transfected CHO cells. Enzymatic digestions and
      chemical cleavages were then performed on ligand-receptor complexes and fragments
      produced by the lysis were analyzed to point out putative interaction areas on
      the receptors. Results showed that Phe147-Lys166, covering the second segment of
      EC I and the top part of TM III, contains a contact point for [Nle7, L-Bpa12,
      Tyr(125I)13]hET-1 on ETA receptors whereas Ile292-Trp319, spanning from the
      second half of the intracellular loop III up to the middle turns of TM VI,
      includes a residue that can interact with [L-Bpa7, Tyr(125I)13]hET-1. Moreover,
      upon binding of [Nle7, L-Bpa12, Tyr(125I)13]hET-1, it was observed that Thr263
      Met266 (EC II) of the ETB receptor would come close with the ligand.

PMID- 18343230
TI  - The inhibitory action of SQDG (sulfoquinovosyl diacylglycerol) from spinach on
      Cdt1-geminin interaction.
AB  - A human replication initiation protein, Cdt1, is a central player in the cell
      cycle regulation of DNA replication, and geminin down-regulates Cdt1 function by
      direct binding. It has been demonstrated that Cdt1 hyperfunction resulting from
      Cdt1-geminin imbalance, for example, by geminin silencing with small interfering
      RNA, induces DNA re-replication and eventual cell death in some cancer-derived
      cell lines. We established a high throughput screening system based on a modified
      enzyme linked immunosorbent assay to identify compounds that interfere with human
      Cdt1-geminin binding. Using this system, we screened inhibitors from natural
      materials containing food components, and found that a glycolipid,
      sulfoquinovosyl diacylglycerol (SQDG), from spinach can inhibit Cdt1-geminin
      interaction in vitro, with 50% inhibition observed at concentrations of
      1.79mug/ml. Other major glycolipids, such as monogalactosyl diacylglycerol (MGDG)
      and digalactosyl diacylglycerol (DGDG) from spinach, had no influence. Surface
      plasmon resonance analysis demonstrated that SQDG bound selectively to Cdt1, but
      did not interact with geminin. Using three-dimensional computer modeling
      analysis, SQDG was considered to interact with the geminin interaction interface
      on Cdt1, and the sulfate group of SQDG was assumed to make hydrogen bonds with
      the residue of Arg346 of Cdt1. These data could help to further understanding of
      the structure and function of Cdt1. In addition, SQDG could be a clue to
      developing more appropriate inhibitors of Cdt1-geminin interactions.

PMID- 18343231
TI  - Ligands playing musical chairs with G-quadruplex DNA: a rapid and simple
      displacement assay for identifying selective G-quadruplex binders.
AB  - We report here the details of G4-FID (G-quadruplex fluorescent intercalator
      displacement), a simple method aiming at evaluating quadruplex-DNA binding
      affinity and quadruplex- over duplex-DNA selectivity of putative ligands. This
      assay is based on the loss of fluorescence upon displacement of thiazole orange
      from quadruplex- and duplex-DNA matrices. The original protocol was tested using
      various quadruplex- and duplex-DNA targets, and with a wide panel of G-quadruplex
      ligands belonging to different families (i.e. from quinacridines to metallo
      organic ligands) likely to display various binding modes. The reliability of the
      assay is further supported by comparisons with FRET-melting and ESI-MS assays.

PMID- 18343232
TI  - Expanding the specificity of DNA targeting by harnessing cooperative assembly.
AB  - The precise control of developmental and regulatory processes in the cell
      requires accurate recognition of specific DNA sites. For genomes as large as that
      of humans, single-molecule-DNA binders have difficulties accurately and
      specifically recognizing the intended targets. Natural transcription factors
      overcome these difficulties by forming non-covalent complexes on the DNA with
      other transcription factors. These cooperative complexes overcome the
      difficulties of single-molecule transcription factors, allowing specific,
      combinatorial control of a range of transcriptional targets. Artificial
      transcription factors have been designed to take advantage of this technique of
      cooperative assembly, facilitating future studies in whole genome targeting. In
      contrast to a simple model of component independence, cooperative complexes as a
      whole often display slightly altered DNA specificity from what would be expected
      from the analysis of their separate components. The true sequence specificity of
      cooperative complexes, and thus their presumed in vivo targets, have to be
      experimentally probed. A number of techniques, such as the cognate site identity
      array, now allow for rapid, high-throughput determination of the specificity of
      cooperative complexes.

PMID- 18343233
TI  - Unique gene organization of colubrid three-finger toxins: complete cDNA and gene
      sequences of denmotoxin, a bird-specific toxin from colubrid snake Boiga
      dendrophila (Mangrove Catsnake).
AB  - Denmotoxin is a colubrid three-finger toxin isolated from the venom of Boiga
      dendrophila, which exhibits bird-specific neurotoxicity. We have sequenced the
      full-length cDNA and the gene encoding the precursor of denmotoxin. This is the
      first glimpse of genomic organization of a colubrid three-finger toxin.
      Denmotoxin cDNA shows low similarity to elapid three-finger toxins, except for
      the conserved signal peptide region. The open reading frame of denmotoxin
      possesses an additional fragment encoding a part of the putative signal peptide
      followed by an extra long N-terminus. The exon/intron organization of denmotoxin
      is also different from elapid three-finger toxin genes. The denmotoxin gene
      contains four exons and three introns, while elapid genes share virtually
      identical gene organization consisting of three exons and two introns. It appears
      that Elapidae snakes have lost the extra second exon after the divergence of the
      snake families.

PMID- 18343234
TI  - All along the watchtower: is the cilium a tumor suppressor organelle?
AB  - Cilia or flagella have been around since almost the beginning of life, and have
      now developed specialized cell-type specific functions from locomotion to acting
      as environmental sensors participating in cell signalling. Genetic defects
      affecting cilia result in a myriad of pathological instances, including
      infertility, obesity, blindness, deafness, skeletal malformations, and lung
      problems. However, the consistency in which the common kidney cyst is coupled
      with cilia dysfunction has raised interest in the possibility that ciliary
      dysfunction might contribute to other neoplasms as well. A suite of recent papers
      convincingly linking cilia to hedgehog signalling, platelet-derived growth factor
      signalling, Wnt signalling and the von Hippel-Lindau tumor suppressor protein has
      rapidly expanded the knowledge base connecting cilia to cancer. We propose that
      these data support the notion of the cilium as a cellular Watchtower, whose
      absence can be an initiating event in neoplastic growth. Furthermore, we predict
      that we are just now seeing the tip of the iceberg, and that the list of cancers
      associated with altered ciliary signalling will grow exponentially in the next
      few years.

PMID- 18343235
TI  - Maternal nicotine exposure increases oxidative stress in the offspring.
AB  - Fetal and neonatal nicotine exposure causes beta-cell apoptosis and loss of beta
      cell mass, but the underlying mechanisms are unknown. The goal of this study was
      to determine whether maternally derived nicotine can act via the pancreatic
      nicotinic acetylcholine receptor (nAChR) during fetal and neonatal development to
      induce oxidative stress in the pancreas. Female Wistar rats were given saline or
      nicotine (1 mg/kg/day) via subcutaneous injection for 2 weeks prior to mating
      until weaning (postnatal day 21). In male offspring, nAChR subunit mRNA
      expression was characterized in the developing pancreas and various oxidative
      stress markers were measured at weaning following saline and nicotine exposure.
      The nAChR subunits alpha2-alpha4, alpha6, alpha7, and beta2-beta4 were present in
      the pancreas during development. Fetal and neonatal exposure to nicotine
      significantly increased pancreatic GPx-1 and MnSOD protein expression, as well as
      islet ROS production. Furthermore, protein carbonyl formation was higher in
      nicotine-exposed offspring relative to controls, particularly within the
      mitochondrial fraction. There was also a nonsignificant trend toward higher serum
      8-isoPG levels. These data suggest that beta-cell apoptosis in the fetal and
      neonatal pancreas may be the result of a direct effect of nicotine via its
      receptor and that this effect may be mediated through increased oxidative stress.

PMID- 18343236
TI  - Oxygen induces mutation in a strict anaerobe, Prevotella melaninogenica.
AB  - Strict anaerobes are highly sensitive to oxygen, but the mutagenicity of oxygen
      in strict anaerobes has not been well understood. Prevotella melaninogenica, a
      strict anaerobe, is susceptible to oxygen and shows an increase in oxidative DNA
      damage upon exposure to oxygen. In this study, we have investigated the
      mutagenicity of oxygen and the types of mutations induced by oxygen. Exposure to
      oxygen decreased cell survival and increased the levels of 8-oxo-deoxyguanosine
      (8-oxodG). The frequency of rifampicin-resistant mutants was markedly increased
      after exposure to oxygen. After sequencing a 254-bp fragment of the rpoB gene,
      which encodes the beta subunit of bacterial RNA polymerase, a target molecule of
      rifampicin, we found that most mutants induced by oxygen had GC to TA
      transversions, a signature of 8-oxodG. In addition, all detected single
      nucleotide changes would lead to amino acid changes that confer rifampicin
      resistance. These results indicate that oxygen is mutagenic in a strict anaerobe,
      P. melaninogenica, and its mutagenic characteristics could be analyzed with this
      experimental system.

PMID- 18343237
TI  - Cataract mutation P20S of alphaB-crystallin impairs chaperone activity of alphaA
      crystallin and induces apoptosis of human lens epithelial cells.
AB  - Cataract is a common cause of childhood blindness worldwide. alpha-crystallin,
      which is comprised of two homologous subunits, alphaA- and alphaB-crystallin,
      plays a key role in the maintenance of lens transparency. Recently, we have
      identified a missense mutation in alphaB-crystallin that changes the proline
      residue at codon 20 to a serine residue (P20S) in a large Chinese family with
      autosomal dominant posterior polar congenital cataract. To explore the molecular
      mechanism by which the P20S mutation causes cataract, we examined the quaternary
      structure, subunit exchange and chaperone activity of the reconstituted
      heteroaggregates of alpha-crystallins containing wild type (WT) alphaA in
      combination with either WT-alphaB- or mutant alphaB-crystallin, respectively.
      Compared with heteroaggregates of WT-alphaA and WT-alphaB, heteroaggregates
      containing WT-alphaA and mutant alphaB showed nearly the same molecular mass, but
      the subunit-exchange rate and chaperone activity were decreased markedly. In
      human lens epithelial cells, unlike WT-alphaB-crystallin, the P20S mutant protein
      showed abnormal nuclear localization, and unusual ability to trigger apoptosis.
      These results suggest that the changes in the structure and function of the alpha
      crystallin complex and cytotoxicity are vital factors in the pathogenesis of
      congenital cataract linked to the P20S mutation in the alphaB-crystallin.

PMID- 18343239
TI  - Pharmacokinetic/pharmacodynamic profile of mometasone furoate nasal spray:
      potential effects on clinical safety and efficacy.
AB  - BACKGROUND: Mometasone furoate nasal spray (MFNS) is recommended as a first-line
      therapy for allergic rhinitis. The purpose of intranasal administration is to
      deliver maximally effective therapy to the affected nasal tissues while
      minimizing systemic exposure. OBJECTIVE: This article reviews the pharmacokinetic
      and pharmacodynamic properties of MFNS, highlighting the potential clinical
      relevance of data concerning its glucocorticoid receptor binding,
      bioavailability, and metabolism, and its role in activating and suppressing
      transcription of steroid-dependent genes. METHODS: A search of the MEDLINE and
      EMBASE databases (January 1995-July 2007) was undertaken to identify in vitro,
      preclinical, and clinical studies and review articles concerning MFNS. Searches
      were also conducted to identify articles on the pharmacokinetics,
      pharmacodynamics, and adverse effects of the intranasal corticosteroids discussed
      in this article. Pertinent abstracts from allergy society meetings and data from
      the author's research experience were also included. RESULTS: The data reviewed
      indicate that MFNS has a number of qualities that are important in achieving
      nasal selectivity with minimal systemic adverse effects. For example, MFNS is
      stable in nasal tissues and is efficiently metabolized in the liver (AUC for a
      400-microg dose: 127 fmol/mL x h). Its systemic bioavailability (0.46%) is one of
      the lowest among currently available intranasal corticosteroids. Bioactive
      glucocorticoid metabolites have not been observed in humans. The results of
      immunologic studies suggest that MFNS may reverse the exaggerated T-helper cell
      type 2 (Th2)-related cytokine response seen in allergic disease through
      preferential inhibition of Th2 over the T-helper cell type 1-related cytokine.
      CONCLUSIONS: MFNS is an intranasal corticosteroid with a low potential for
      systemic adverse effects. The efficacy and safety profiles of MFNS seen in
      clinical use are consistent with its pharmacokinetic and pharmacodynamic
      properties.

PMID- 18343240
TI  - Panitumumab: human monoclonal antibody against epidermal growth factor receptors
      for the treatment of metastatic colorectal cancer.
AB  - BACKGROUND: Panitumumab, formerly known as ABX-EGF, was the first recombinant
      human immunoglobulin G2 monoclonal antibody approved by the US Food and Drug
      Administration for the treatment of patients with epidermal growth factor
      receptor-expressing metastatic colorectal cancer (mCRC) refractory to
      fluoropyrimidine-, oxaliplatin-, and/or irinotecan-containing chemotherapeutic
      regimens. OBJECTIVE: The purpose of this review was to evaluate the
      pharmacokinetic and pharmacodynamic properties, clinical efficacy, and safety
      profile of panitumumab in the treatment of metastatic colorectal cancer. METHODS:
      Computerized searches of MEDLINE and International Pharmaceutical Abstracts from
      1985 to August 15, 2007, were performed with the search terms panitumumab, ABX
      EGF, EGFr, and colorectal cancer. All available clinical trials and ongoing
      trials were included in this review. Relevant abstracts presented at the annual
      meetings of the American Society of Clinical Oncology, American Association for
      Cancer Research, and Gastrointestinal Cancer Symposium (1999-2007) also were
      reviewed and included. RESULTS: Preclinical and clinical studies have established
      a role for panitumumab in mCRC refractory to multiple chemotherapeutic regimens.
      In a Phase III trial of panitumumab plus best supportive care (BSC) versus BSC
      alone in patients with refractory mCRC, panitumumab was found to have efficacy in
      time-related end points, such as progression-free survival. In the panitumumab
      group, a significant (46%) reduction in tumor progression rate was reported
      compared with BSC (hazard ratio, 0.54; 95% CI, 0.44-0.66; P < 0.001). At the
      present time, the use of panitumumab as first-line treatment for mCRC with
      standard chemotherapy and bevacizumab is not indicated due to increased toxicity
      with no advantage in efficacy. The efficacy of panitumumab is being evaluated in
      other solid tumors, such as lung, breast, ovarian, bladder, and head and neck
      cancers. CONCLUSION: Panitumumab appears to have relatively acceptable
      tolerability and is now available as an additional option for patients with mCRC
      refractory to multiple chemotherapeutic regimens.

PMID- 18343241
TI  - Aliskiren: renin inhibitor for hypertension management.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) has long been
      recognized to play a significant role in hypertension pathophysiology. Certain
      agents that modify the RAAS can control blood pressure and improve cardiovascular
      outcomes. Aliskiren is the first of a new class of antihypertensive agents known
      as renin inhibitors. OBJECTIVE: The goal of this article was to discuss the
      clinical pharmacology of aliskiren and its use in the management of hypertension,
      as well as potential uses in other cardiovascular disorders. METHODS: Peer
      reviewed articles and abstracts were identified from the MEDLINE and Current
      Contents databases (both 1966-October 1, 2007) using the search terms aliskiren,
      drug interaction, pharmacokinetics, and pharmacology. Citations from available
      articles were reviewed for additional references. Abstracts presented at recent
      professional meetings were also examined. RESULTS: Nine published clinical
      studies have evaluated the effect of aliskiren in lowering blood pressure in
      hypertensive patients, either alone or in combination with other antihypertensive
      agents. This review summarizes those studies. Patients treated with aliskiren had
      significantly lower blood pressure compared with patients with mild to moderate
      hypertension (systolic blood pressure [SBP] 140-180 mm Hg and diastolic blood
      pressure [DBP] 95-110 mm Hg) who received placebo. Aliskiren in doses of 75 to
      300 mg daily produced reductions of SBP (-5.3 to -15.8 mm Hg) and DBP (-5.8 to 
      12.3 mm Hg); placebo produced reductions of SBP that ranged from -2.85 to -10.0
      mm Hg and DBP reductions from -3.26 to -8.6 mm Hg (P < 0.05 in all studies
      between aliskiren and placebo). Aliskiren's blood pressure-lowering effect at
      doses of 75 to 300 mg daily was comparable to irbesartan 150 mg daily and
      valsartan 80 to 360 mg daily alone. When aliskiren was added to ramipril,
      hydrochlorothiazide, amlodipine, irbesartan, or valsartan, significant additive
      blood pressure-lowering effects were reported (P < 0.05 in all clinical trials).
      The total incidence of adverse events was similar to placebo and other
      comparative agents, including irbesartan, valsartan, losartan, ramipril, and
      hydrochlorothiazide. The overall adverse-event rates were 22%, 35% to 52%, 25% to
      52%, 34% to 55%, and 33% to 52% for aliskiren 37.5, 75, 150, 300, and 600 mg,
      respectively. The most commonly reported adverse events included headache,
      dizziness, and fatigue. Studies with cardiovascular outcomes as end points have
      not been performed with aliskiren. CONCLUSIONS: Aliskiren is an effective
      alternative agent for blood pressure management. Before aliskiren can be
      recommended as a routine first-line agent, however, clinical studies must explore
      if the blood pressure-lowering effect will translate into improvement in
      cardiovascular outcomes.

PMID- 18343242
TI  - Comparison of two marketed nifedipine modified-release formulations: an
      exploratory clinical food interaction study.
AB  - OBJECTIVE: The objective of this study was to compare the in vitro and in vivo
      characteristics of 2 nifedipine modified-release tablet formulations for once
      daily dosing marketed in the European community, which were expected to be
      bioequivalent. METHODS: In vitro dissolution was tested at different pH values
      prior to the clinical part of the study. Either 1 tablet of a test formulation or
      of the reference formulation, both containing 30 mg nifedipine, were administered
      to healthy white male volunteers immediately after a high-fat breakfast in a
      randomized, open-label, 2-period crossover design. Plasma samples obtained over
      the subsequent period of 48 hours were analyzed using a validated LC-MS/MS
      method. Safety profile and tolerability of the study medications were assessed by
      analysis of adverse events obtained by vital sign measurements,
      electrocardiography, and clinical laboratory analysis. RESULTS: Twelve volunteers
      were enrolled (median age, 28.0 years [range, 21-42 years]; mean body mass index,
      24.2 kg/m(2) [range, 19.3-27.0 kg/m(2)]). In vitro dissolution experiments
      revealed a significant pH dependency in drug release from the investigational
      tablets, while the reference tablets were found to have pH-independent
      dissolution. After oral administration of both tablet formulations in the fed
      state, marked differences in rate and extent of bioavailability were observed.
      Geometric mean of AUC(0-last)(test, 504.21 h x ng/mL; reference, 361.28 h x
      ng/mL) was significantly higher for the test product, with a point estimate of
      140% and a corresponding 90% CI of 121% to 161%. For the comparison of Cmax
      values, geometric means were: test, 76.46 ng/mL; reference, 19.20 ng/mL, with a
      point estimate of 398% and a CI of 316% to 503%. Thus, a significant difference
      in rate and extent of bioavailability was observed between the 2 products.
      CONCLUSIONS: Although both treatments were well tolerated by all volunteers, the
      test and reference tablets were found to have different pharmacokinetic
      properties when administered after a high-fat meal.

PMID- 18343243
TI  - Comparative bioavailability of single-dose methylphenidate from a multilayer
      release bead formulation and an osmotic system: a two-way crossover study in
      healthy young adults.
AB  - OBJECTIVE: This study was conducted to compare plasma levels of methylphenidate
      over time with single doses of a multilayer-release (MLR) bead formulation and an
      osmotic, controlled-release oral delivery system (OROS) of methylphenidate in
      young adults. METHODS: This was a randomized, 2-way crossover study in which
      healthy, nonsmoking young adults (age 18-25 years) were randomized to receive
      methylphenidate MLR 20 mg QD or OROS methylphenidate 18 mg QD, with a 7-day
      washout between treatments. Plasma samples were collected before dosing and at
      0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10,
      12, 14, 16, and 24 hours after dosing. Analysis of plasma samples was conducted
      by high-performance liquid chromatography with tandem mass-spectrometry
      detection. Adverse events were monitored by spontaneous reports, laboratory and
      biochemistry tests, urinalysis, and physical examinations conducted at screening
      and at the end of the study. RESULTS: Of the 24 subjects originally enrolled, 3
      discontinued for personal reasons after the first phase and were not included in
      the pharmacokinetic analysis. The per-protocol population (11 females, 10 males)
      had a mean (SD) age of 22 (2) years (range, 19-25 years) and a mean body mass
      index of 23.6 (3.0) kg/m(2) (range, 19.0-28.5 kg/m(2)). The relative AUC0t and
      Cmax ratios for the MLR methylphenidate formulation compared with the OROS
      methylphenidate formulation were 110.88% and 121.84%, respectively. When OROS
      methylphendate values were dose normalized to 20 mg, the relative AUC0-t and Cmax
      ratios were 100.72% and 111.82%. The mean Tmax for the 2 formulations was 3.71
      (2.03) and 4.96 (2.56) hours. Values were significantly higher with the MLR
      methylphenidate formulation compared with the OROS methylphenidate formulation
      for AUC(0-4) (P < 0.001), AUC(0-8) (P < 0.001), AUC(0-12) (P < 0.001), and AUC(4
      12) (P = 0.037); the AUC(8-12) was not significantly different between the 2
      formulations. Values were significantly higher for the MLR methylphenidate
      formulation relative to the OROS methylphenidate formulation for C(max0-4) (P <
      0.001) and C(max4-12) (P = 0.002). Thirty-seven adverse events occurred in 11 and
      10 subjects during receipt of MLR and OROS methylphenidate, respectively. The
      most commonly reported adverse events in the intent-to-treat population were
      catheter-site pain, reported by 8 of 24 subjects (33.3%), and headache, reported
      by 5 of 24 subjects (20.8%). CONCLUSIONS: In these healthy young subjects, MLR
      methylphenidate was associated with a concentration-time profile that resulted in
      a higher proportion of the administered methylphenidate dose being delivered in
      the first 4 hours after dosing compared with OROS methylphenidate while
      maintaining comparable levels of drug in the latter portion of the dosing
      interval. This led to maintenance of higher mean levels of methylphenidate
      throughout the day compared with the closest marketed dose of OROS
      methylphenidate. The 2 formulations are marketed in dissimilar strengths;
      however, after correction for administered dose, they yielded similar AUC values.

PMID- 18343244
TI  - Analgesic effectiveness of celecoxib and diclofenac in patients with
      osteoarthritis of the hip requiring joint replacement surgery: a 12-week,
      multicenter, randomized, double-blind, parallel-group, double-dummy,
      noninferiority study.
AB  - BACKGROUND: The hip is the second most common large joint that is affected by
      osteoarthritis (OA), with prevalence ranging from 3% to 11% in patients aged > or
      = 35 years. OA is often associated with significant pain, disability, and
      impaired quality of life. Treatment should be tailored according to the level of
      pain, disability, and handicap. Pharmacologic treatment options for hip OA
      include acetaminophen (recommended by the European League Against Rheumatism as a
      first-line treatment), NSAIDs such as diclofenac, and cyclooxygenase-2-selective
      NSAIDs such as celecoxib. OBJECTIVE: The purpose of this study was to determine
      whether celecoxib 200 mg QD is noninferior to diclofenac 50 mg TID in the
      treatment of OA of the hip. METHODS: This was a 12-week, randomized, double
      blind, parallel-group, double-dummy, noninferiority study conducted at 40 centers
      in the United Kingdom. Patients with OA flare at baseline (determined by visual
      analog scale [VAS] measurement of > or = 40 to < 90 mm and patient's and
      physician's global assessments of arthritis ratings of "poor" or "very poor") and
      awaiting joint replacement surgery were randomized to receive celecoxib QD or
      diclofenac TID. Patients were excluded if surgery was anticipated within 8 weeks.
      The United Kingdom National Health Service initiatives on waiting-list times
      caused a reduction in the number of potential patients available for
      participation. Therefore, the study protocol was amended such that change from
      baseline to week 6 (as opposed to week 12) in the patient's assessment of
      arthritis pain on walking, measured by VAS (0-100 mm), was the primary outcome.
      Primary analysis was carried out on the evaluable population (subjects with
      baseline and week 6 arthritis pain on walking VAS scores and no major protocol
      deviations). Celecoxib was declared noninferior to diclofenac if the upper limit
      of the 2-sided 95% CI of the treatment difference (celecoxib vs diclofenac) in
      the mean change from baseline in VAS did not exceed 10 mm. Tolerability was
      assessed by the documentation of observed and volunteered adverse events (AEs),
      physical examination findings, sitting blood pressure, and pulse at screening and
      at the end of the study (week 12 or early withdrawal). RESULTS: A total of 249
      patients aged > or = 45 years were randomized to treatment. There were 126
      patients in the celecoxib group and 123 patients in the diclofenac group. One
      patient in the celecoxib group did not receive any treatment and was excluded
      from analysis. Additionally, 54 patients in the celecoxib group and 45 patients
      in the diclofenac group discontinued treatment due to AEs and/or lack of
      treatment effectiveness. Therefore, 71 patients in the celecoxib group and 78
      patients in the diclofenac group completed the study. No significant differences
      in demographic characteristics were observed between treatment groups. The mean
      (SD) age was 64.0 (9.0) years, 53.9% (76/141) of the patients were men and 46.1%
      (65/141) were women, and 99.3% (140/141) were white. At weeks 6 and 12, the
      patient's assessment of arthritis pain on walking (VAS) improved in both groups (
      20.0 [23.6] mm in the celecoxib group and -35 [27.0] mm in the diclofenac group
      [mean treatment difference, 14.4 mm; 95% CI, 6.1 to 22.7]). However, treatment
      differences in change from baseline favored diclofenac at week 6 (14.4 mm; 95%
      CI, 6.1 to 22.7) and week 12 (12.2 mm; 95% CI, 2.2 to 22.1). A post hoc analysis,
      performed after unblinding due to an imbalance in the numbers of patients
      previously receiving NSAIDs, found a greater treatment difference at week 6
      between celecoxib and diclofenac in arthritis pain, favoring diclofenac, in
      previous nonusers of NSAIDs (n = 49, 18.6 mm; 95% CI, 4.5 to 32.8) compared with
      previous NSAID users (n = 92, 9.5 mm; 95% CI, -0.4 to 19.3). Celecoxib and
      diclofenac were generally well tolerated. A similar proportion of patients in
      both treatment groups experienced AEs (all causality): 67/125 of celecoxib
      treated patients (53.6%) compared with 66/123 of diclofenac-treated patients
      (53.7%). CONCLUSION: This study did not demonstrate noninferiority of celecoxib
      200 mg QD to diclofenac 50 mg TID in treating arthritis pain in patients with OA
      of the hip requiring joint replacement.

PMID- 18343245
TI  - Effects of fluvastatin extended-release (80 mg) alone and in combination with
      ezetimibe (10 mg) on low-density lipoprotein cholesterol and inflammatory
      parameters in patients with primary hypercholesterolemia: a 12-week, multicenter,
      randomized, open-label, parallel-group study.
AB  - BACKGROUND: Combining lipid-lowering agents with complementary mechanisms of
      action can provide greater cholesterol reductions than using either agent alone,
      improving achievement of target low-density lipoprotein cholesterol (LDL-C)
      levels. OBJECTIVES: The aim of this study was to assess the effects of
      fluvastatin extended-release (XL) 80 mg/d administered alone or combined with
      ezetimibe 10 mg/d on plasma lipid levels and inflammatory parameters in patients
      with primary hypercholesterolemia. The tolerability of both regimens was also
      evaluated. METHODS: In this multicenter, randomized, open-label, parallel-group
      study, patients with hypercholesterolemia were randomized in a 1:1 ratio to
      receive fluvastatin XL 80 mg/d alone or in combination with ezetimibe 10 mg/d for
      12 weeks. The primary end point was the percentage change from baseline to week
      12 in LDL-C level with fluvastatin XL + ezetimibe combination therapy compared
      with fluvastatin XL alone. Plasma concentrations of inflammatory biomarkers were
      measured at baseline and week 12. Proportions of patients who achieved National
      Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C
      goals were calculated. Tolerability was assessed by the monitoring and recording
      of all adverse events (AEs) and laboratory values. RESULTS: A total of 82
      patients were enrolled (mean [SD] age, 50.0 [12.0] years; 44% male; 100% white;
      mean [SD] weight, 73.5 [14.9] kg; combination group, 38 patients; monotherapy
      group, 44). Fluvastatin XL + ezetimibe and fluvastatin XL monotherapy were
      associated with significant decreases from baseline in mean LDL-C level (by 49.9%
      and 35.2%, respectively; between-group difference, P < 0.001). Fluvastatin XL +
      ezetimibe was associated with significantly greater reductions from baseline than
      fluvastatin XL monotherapy in total cholesterol (38.2% vs 27.5% P < 0.001),
      triglycerides (21% vs 3.8% P = 0.02) and apolipoprotein B (34.8% vs 22.5% P <
      0.001). NCEP ATP III LDL-C goals were achieved by 87% of patients receiving
      fluvastatin XL + ezetimibe and 67% of patients receiving fluvastatin XL
      monotherapy (between-group difference, P = 0.042). The combination was associated
      with significantly lowered high-sensitivity C-reactive protein (hs-CRP) levels in
      patients with high baseline hs-CRP (>2 mg/L; P < 0.02), >1 cardiovascular risk
      factor (P < 0.05), or hypertension (P = 0.015); both regimens were associated
      with significantly reduced plasma levels of interleukin-1B. No significant
      between-group differences in the incidences of AEs were found. Most AEs were mild
      or moderate in intensity. Headache was the most common AE, occurring in 5/44
      (11.4%) patients in the fluvastatin XL group and 2/38 (5.3%) patients in the
      fluvastatin XL + ezetimibe group. One serious AE (convulsive crisis) occurred in
      a patient receiving fluvastatin XL + ezetimibe, but was not suspected to be
      related to study medication. CONCLUSION: Fluvastatin XL in combination with
      ezetimibe was found to be well-tolerated and effective, allowing the majority
      (87%) of these patients with primary hypercholesterolemia to achieve current
      treatment goals, and reduced hs-CRP levels in patients at higher cardiovascular
      risk.

PMID- 18343246
TI  - Comparison of the effects of doxazosin and atenolol on target organ damage in
      adults with type 2 diabetes mellitus and hypertension in the CARDHIAC study: a 9
      month, prospective, randomized, open-label, blinded-evaluation trial.
AB  - OBJECTIVE: The CARDHIAC (CARduran en pacientes Diabeticos con HIpertensi'on
      Arterial no Controlada) trial examined the effects of doxazosin gastrointestinal
      therapeutic system (GITS) and atenolol on 3 separate measures of target-organ
      damage--left ventricular mass index (LVMI), carotid intima media thickness (IMT),
      and urinary albumin excretion (UAE)--in patients with type 2 diabetes mellitus
      and hypertension. METHOD: This trial had a prospective, open-label, blinded
      evaluation design and a duration of 9 months. Patients whose blood pressure (BP)
      was uncontrolled (systolic BP > or = 130 mm Hg and/or diastolic BP > or = 80 mm
      Hg) despite at least 1 month of treatment with a renin-angiotensin blocker and
      diuretic were randomly allocated to receive doxazosin GITS 4 mg or atenolol 50 mg
      once daily in addition to their existing treatment. Seated BP was measured at
      study visits at 1, 3, 6 and 9 months; if the BP goal was not achieved at any
      visit, the dose of doxazosin or atenolol was titrated upward to 8 or 100 mg,
      respectively. Treatment compliance (pill count) and adverse reactions were
      monitored at each visit. Each patient underwent echocardiography and Doppler
      ultrasonography at baseline and at the end of the study for evaluation of the
      change in LVMI. The change in carotid IMT was evaluated by carotid ultrasound
      examination at the same time points. UAE also was measured at baseline and the
      end of the study. RESULTS: Sixty patients (100% white; 51% female; mean [SD] age,
      63.4 [7.5] years; body mass index, 28.2 [3.4] kg/m(2)) were randomized to receive
      doxazosin GITS (n=32) or atenolol (n=28). At baseline, mean BP was 150.2
      (10.6)/90.1 (7.3) mm Hg in the doxazosin group and 153.1 (13.8)/92.3 (6.1) mm Hg
      in the atenolol group (P=NS). At the end of the study, BP had decreased by 10.1
      (3.2)/5.2 (1.3) mm Hg in the doxazosin group and 12.2 (4.2)/6.3 (2.1) mm Hg in
      the atenolol group (both, P<0.001 vs baseline; P=NS between groups). Heart rate
      at the end of the study was 78(6) beats/min in the doxazosin group (P=NS vs
      baseline) and 66(7) beats/min in the atenolol group (P<0.01 vs baseline and
      between groups). LVMI decreased by 10.8 in the doxazosin group (P=0.001 vs
      baseline) and 4.2% in the atenolol group (P=NS vs baseline; P=0.03 between
      groups). The changes in carotid IMT and UAE were not statistically significant
      between groups. CONCLUSIONS: In this study in hypertensive patients with type 2
      diabetes, LVMI was significantly decreased in doxazosin-treated patients relative
      to baseline and compared with atenolol-treated patients. The differences in
      carotid IMT and UAE were not statistically significant between groups.

PMID- 18343247
TI  - Ambulatory blood pressure-lowering effects of valsartan and enalapril after a
      missed dose in previously untreated patients with hypertension: a prospective,
      randomized, open-label, blinded end-point trial.
AB  - BACKGROUND: Approximately 3 days a month, some 15% to 20% of patients with
      hypertension do not recall having taken their antihypertensive medication.
      Individuals with this frequency of missed doses may be at increased risk for a
      cardiovascular event and may have a poorer long-term prognosis. OBJECTIVE: This
      study used ambulatory blood pressure monitoring (ABPM) to compare the blood
      pressure (BP)-lowering effects of valsartan and enalapril over the 24 hours after
      missing 1 dose in previously untreated patients with mild to moderate essential
      hypertension. METHODS: This was a prospective, randomized, open-label, parallel
      group, blinded end-point trial in previously untreated patients (age >18 years)
      with mild to moderate essential hypertension (European Society of Hypertension
      European Society of Cardiology guidelines: systolic BP 140-179 mm Hg or diastolic
      BP 90-109 mm Hg). Patients were randomly assigned to receive 16 weeks of
      treatment with valsartan 160 mg/d or enalapril 20 mg/d, taken on waking. ABPM was
      conducted for 48 consecutive hours at baseline and again after 16 weeks of
      therapy. Patients took a dose of their assigned treatment at the beginning of the
      final session of ABPM and were instructed to skip the next daily dose. RESULTS:
      The study enrolled 148 Spanish patients (84 men, 64 women; mean [SD] age, 45.8
      [10.7] years) with previously untreated hypertension. At the end of treatment,
      there were significant differences between groups during the first 24 hours of
      ABPM, starting in the final 6 hours of the dosing interval (P < 0.001). There was
      no significant change in BP reduction between the first and second 24-hour
      periods of ABPM with valsartan (-2.1/-1.4 mm Hg), whereas enalapril was
      associated with a significant increase in BP over this period (5.5/3.8 mm Hg; P <
      0.001 vs first 24 hours; P = 0.032 vs valsartan). CONCLUSIONS: In this study in
      previously untreated patients with mild to moderate essential hypertension,
      valsartan was associated with a sustained BP-lowering effect beyond the initial
      24 hours after dosing, whereas enalapril was not. There was no significant change
      in the efficacy of valsartan in the 24 hours after a missed dose. At the doses
      tested, valsartan was more effective than enalapril, both during active treatment
      and after a missed dose.

PMID- 18343248
TI  - A case-control study of the association between polymorphisms of the endothelial
      nitric oxide synthase and glycoprotein IIIa genes and upper gastrointestinal
      bleeding in users of low-dose aspirin.
AB  - BACKGROUND: Previous studies have reported a potential genetic predisposition to
      NSAID-related upper gastrointestinal (GI) bleeding. OBJECTIVE: This study
      evaluated whether there was an association between 2 polymorphisms--the platelet
      glycoprotein (GP) IIIa PlA1/A2 polymorphism and the 27-bp VNTR (variable number
      of tandem repeats) polymorphism in intron 4 of the endothelial nitric oxide
      synthase (eNOS) gene--and a risk for nonvariceal upper GI bleeding in Spanish
      patients taking low-dose aspirin for secondary prophylaxis of vascular occlusive
      diseases. METHODS: Genotyping for the 2 polymorphisms was performed in patients
      hospitalized for upper GI bleeding associated with the use of low-dose aspirin
      between September 1998 and October 2000, and race-, age-, and sex-matched
      controls who were taking low-dose aspirin but had no history of upper GI
      bleeding. To ascertain allele frequencies in a healthy population, genotyping was
      also performed in an unmatched group of blood donors. RESULTS: The study included
      88 white patients (65 men, 23 women; mean age, 67.5 years) with an episode of
      upper GI bleeding, 108 matched controls with no history of upper GI bleeding (79
      men, 29 women; mean age, 65.9 years), and 158 blood-donor controls (109 men, 49
      women; mean age, 53.4 years). No significant differences were found between cases
      and controls in terms of genotype, carriage, or allele frequency of the GPIIIa
      PlA1/A2 polymorphism. However, after adjustment for confounding variables,
      logistic regression analysis indicated an association between carriage of the
      eNOS "a" allele and a reduced risk of upper GI bleeding (odds ratio [OR] 0.39; 95
      CI, 0.18-0.85; P 0.018). In this model, treatment with nitrovasodilators (OR
      0.28; 95 CI, 0.12-0.66; P 0.004) and use of antisecretory drugs (OR 0.15; 95 CI,
      0.05-0.47; P 0.001) were also identified as protective factors. Helicobacter
      pylori infection (OR 3.07; 95 CI, 1.23-7.70; P 0.017), alcohol consumption (OR
      5.04; 95 CI, 1.86-13.70; P 0.001), and a history of peptic ulcer (OR 13.41; 95
      CI, 3.78-47.64; P 0.001) were identified as risk factors for upper GI bleeding.
      CONCLUSION: In this small, selected population of individuals taking low-dose
      aspirin for secondary prevention, carriage of the "a" allele of the eNOS gene was
      associated with a decreased risk for upper GI bleeding.

PMID- 18343249
TI  - Two single-center, double-blind, randomized, placebo-controlled, phase I studies
      to investigate the tolerability and pharmacokinetics of CH-1504, an antifolate,
      in healthy male subjects.
AB  - BACKGROUND: Several studies have suggested that a significant proportion of the
      toxicity profile of the antifolate methotrexate can be attributed to its
      hydroxylated and polyglutamylated metabolites. CH-1504 is an investigational
      antifolate, which is neither hydroxylated or polyglutamylated. OBJECTIVE: The
      purpose of this study was to test the tolerability and pharmacokinetics of single
      and multiple ascending doses of CH-1504. METHODS: Two single-center, double
      blind, randomized, placebo-controlled, Phase I studies were conducted in single
      and multiple ascending-dose designs in healthy male adult volunteers. In the
      single ascending-dose study, subjects were randomized to receive the study drug
      (1, 5, 7.5, 10, 15, or 20 mg) or placebo in a 4:1 ratio. Subjects were under
      clinical supervision for 48 hours following a single oral administration. Follow
      up occurred on days 10 and 30. In the multiple ascending-dose study, subjects
      were randomized to receive the study drug (7.5, 10, or 15 mg) or placebo at a 3:1
      ratio. Subjects received a single oral administration of CH-1504 once daily on
      days 1 through 7, during which time they remained under clinical supervision.
      Follow-up was conducted on days 16 and 30. Tolerability was determined through
      echocardiogram and clinical laboratory tests (eg, hematology, serum biochemistry,
      urinalysis). RESULTS: No clinically significant abnormalities were observed in
      any of the tolerability evaluations. No adverse events were attributed to
      treatment and those that were possibly related (eg, rash, headache, dizziness)
      were all considered mild. Peak plasma concentrations occurred between 1 to 2.5
      hours after administration and the apparent t(1/2) was approximately 3 hours. On
      average, <3.1% of the administered dose was recovered as CH-1504 in the urine in
      the single-dose study and <1.5% in the multiple-dose study. CONCLUSIONS: CH-1504
      appeared to be well tolerated in single administered doses up to 20 mg and daily
      administrations for 7 days up to 15 mg in healthy male volunteers in these
      studies. However, the results of the pharmacokinetic analysis support the
      development of a new formulation to improve the bioavailability before further
      clinical studies are warranted.

PMID- 18343250
TI  - Colistin serum concentrations after intravenous administration in critically ill
      patients with serious multidrug-resistant, gram-negative bacilli infections: a
      prospective, open-label, uncontrolled study.
AB  - BACKGROUND: The emergence of multidrug-resistant nosocomial pathogens, such as
      Pseudomonas aeruginosa and Acinetobacter baumannii, has led to the revival of the
      systemic use of antimicrobial agent colistin in critically ill patients, but only
      limited data are available to define its pharmacokinetic profile in these
      patients. OBJECTIVE: The aim of this study was to assess steady-state serum
      concentrations of colistin after i.v. administration of colistin methanesulfonate
      (CMS) in critically ill patients with stable kidney function. METHODS: This
      prospective, open-label, uncontrolled study was conducted at 2 intensive care
      units in the Athens Trauma Hospital, KAT, Athens, Greece. Adult patients were
      nonconsecutively enrolled if they were critically ill and had stable kidney
      function (<0.5 mg/dL change in serum creatinine prior to and until the day of
      sample collection) and had been receiving CMS as part of a treatment regimen for
      sepsis irrespective of site of infection with multidrug-resistant, gram-negative
      bacilli. After i.v. administration of 225-mg CMS (with the exception of 1 patient
      who received 150 mg) every 8 or 12 hours for at least 2 days, blood samples were
      collected just before and at 10 minutes and 1, 2, 4, 6, and 8 hours after i.v.
      infusion (duration, 30 minutes) of the colistin dose on the sampling day.
      RESULTS: Fourteen nonconsecutive patients were enrolled in the study (13 male, 1
      female; mean [SD] age, 62.0 [19.2] years; mean [SD] estimated weight, 72.5 [8.5]
      kg; mean [SD] Acute Physiology And Chronic Health Evaluation II score on
      admission, 17.1 [6.0]). At steady state, mean (SD) colistin maximum and minimum
      concentrations were 2.93 (1.24) and 1.03 (0.44) mg/L, respectively, while mean
      (SD) apparent total body clearance, apparent volume of distribution, and t(1/2)
      were 13.6 (5.8) L/h, 139.9 (60.3) L, and 7.4 (1.7) hours, respectively. Colistin
      related nephrotoxicity was not observed in the study patients. CONCLUSION: CMS
      dosage regimens administered to these critically ill adult patients were
      associated with suboptimal Cmax/MIC ratios for many strains of gram-negative
      bacilli currently reported as sensitive (MIC, < or = 2 microg/mL).

PMID- 18343251
TI  - Risk factors for hyperglycemia in hospitalized adults receiving gatifloxacin: a
      retrospective, nested case-controlled analysis.
AB  - BACKGROUND: The prevalence of glucose abnormalities has been reported to be
      greater in hospitalized patients receiving gatifloxacin than in patients
      receiving ceftriaxone. OBJECTIVE: The purpose of the current study was to
      identify risk factors for hyperglycemia in hospitalized patients receiving
      gatifloxacin. METHODS: This retrospective, nested case-controlled study was
      conducted in 69 patients and 69 controls in 2 nonteaching hospitals in Houston,
      Texas. Classification and regression tree (CART) analysis was conducted to
      identify break points in continuous variables. Univariate and multivariate
      logistic regression analyses were also performed. RESULTS: A total of 138
      patients (mean [SD] age, 68.3 [17.3] years; weight, 77.4 [21.1] kg; sex, women/
      men, 69.6%/30.4%; race [Hispanic, 58.3%; white, 28.5%; black, 9.2%; other, 4.0%])
      were identified. Patients who developed hyperglycemia (blood glucose level > 200
      mg/dL) within 72 hours of gatifloxacin administration (cases) were matched 1:1
      with patients who received gatifloxacin for > or = 5 days and did not experience
      hyperglycemia during treatment and for 3 days after the end of treatment
      (controls). In univariate analysis, cases were more likely than controls to have
      diabetes (89.9% vs 13.0%; P < 0.001), have a decreased mean (SD) creatinine
      clearance (CrCl) (53.8 [36.8] vs 69.2 [45.3] mL/min; P = 0.025), be located in
      the intensive care unit at the time of the event (20.3% vs 7.2%; P = 0.02), have
      received gatifloxacin doses higher than recommended based on renal function (>
      200 mg/d when CrCl < 40 mL/min) (25/69 [36.2%] vs 9/69 [13.0%]), have
      leukocytosis (mean [SD] white blood cell [WBC] count, 15.5 [7.4] vs 12.8 [6.2]
      cells/mm3), and have received concomitant total parenteral nutrition (7/69
      [10.1%] vs 0 [0%]; P = 0.02) and/or steroids (22/69 [31.9%] vs 8/69 [11.6%]; P =
      0.008). CART analysis identified age > 65 years, albumin < 3.2 g/dL, WBC count >
      14.5 cells/mm3, and CrCl < 40 mL/min to be more common in hyperglycemic patients.
      In logistic regression, diabetes (odds ratio [OR] = 233; 95% CI, 19-2784) and
      excessive dose for renal function (OR = 42; 95% CI, 2-770) were identified as
      independent predictors for hyperglycemia in patients receiving gatifloxacin.
      After controlling for diabetes, concomitant steroids (OR = 5.7; 95% CI, 1.5-21.1)
      and excessive dose for renal function (OR = 4.9; 95% CI, 1.2-20.4) were
      associated with hyperglycemia in patients receiving gatifloxacin. CONCLUSIONS:
      This retrospective, nested case-controlled study found that the risk of
      hyperglycemia increased in diabetic patients who received concomitant steroids or
      higher gatifloxacin doses than recommended by the manufacturer's prescribing
      information. The application of these data should be assessed for other
      fluoroquinolones used at higher doses.

PMID- 18343252
TI  - How Connecticut primary care physicians view treatments for streptococcal and
      nonstreptococcal pharyngitis.
AB  - BACKGROUND: Inappropriate antibiotic treatment of respiratory infections has been
      reported to be common; however, the specifics of this inappropriate treatment are
      not completely defined. OBJECTIVE: The aim of this study was to gather data to
      determine whether physicians consider the national guidelines of treating group A
      B-hemolytic streptococci (GABHS) pharyngitis with penicillin (BID or TID) and not
      using antibiotics to treat nonstreptococcal pharyngitis. METHODS: In this pilot
      survey, a 1-page questionnaire was sent to a random sample of Connecticut primary
      care physicians (PCPs) that included emergency physicians, family physicians,
      internists, and pediatricians. Two short hypothetical scenarios were presented:
      (1) an untreated male patient aged 18 years (who is not penicillin allergic) was
      seen the day before with fever and pharyngitis. He returns because he is still
      symptomatic and his throat culture (TC) is positive for GABHS; and (2) same
      scenario but this second patient's TC is negative for GABHS. Physicians were
      asked how they would treat the patients in both scenarios. RESULTS: Of the 642
      (representing approximately 15% of all Connecticut PCPs) questionnaires sent, 386
      (60%) were returned. Seventy-five of the responding physicians had not seen
      patients with pharyngitis within the last year and were excluded; the following
      results were from 311 physicians. Scenario 1: 191 of 311 physicians (61%)
      indicated a willingness to treat the GABHS with penicillin. Pediatricians were
      significantly less likely, compared with the other PCPs, to prescribe penicillin
      (P = 0.01) in this scenario. Seventy-seven of the 191 physicians (40%) indicated
      a willingness to prescribe the penicillin QID. Seven PCPs who responded to
      scenario 1 did not respond to scenario 2. Scenario 2: 98 of the 304 physicians
      (32%) indicated a willingness to prescribe antibiotics for the patient with no:
      streptococcal pharyngitis. Pediatricians were significantly less likely, compared
      with the other PCPs, prescribe antibiotics for the patient with nonstreptococcal
      pharyngitis in the second scenario (P < 0.001). CONCLUSIONS: This pilot survey
      found that 61% of Connecticut PCPs might treat GABHS with penicillin according to
      existing guidelines although the penicillin might be prescribed QID instead of
      the recommended BID or TID. Thirty-two percent of these PCPs reported they would
      use antibiotics to treat non-GABH pharyngitis.

PMID- 18343253
TI  - Topical amethocaine gel 4% for intramuscular injection in term neonates: a double
      blind, placebo-controlled, randomized trial.
AB  - BACKGROUND: Topical local anesthetic agents such as amethocaine penetrate intact
      skin and block pain signals originating from the dermis during medical
      procedures. They have been found to attenuate pain from various procedures,
      including intramuscular (i.m.) injection of vaccines. Published data on their
      effectiveness for i.m. injection of vitamin K in neonates were not identified.
      OBJECTIVES: The primary objective of this study was to evaluate the analgesic
      effectiveness and tolerability of topical amethocaine gel 4% in neonates
      undergoing i.m. injection of vitamin K. The secondary objective was nurses'
      response to the use of the intervention and possible barriers associated with its
      incorporation into clinical practice. METHODS: In a double-blind, placebo
      controlled, randomized trial, full-term neonates in the Labor and Delivery Unit
      of Mount Sinai Hospital, Toronto, Ontario, Canada, received 1 g of amethocaine
      gel 4% or placebo 30 minutes prior to i.m. injection of 0.5 mL of vitamin K. Pain
      responses were assessed using percent facial grimacing score, percent cry
      duration, and latency to cry from video recordings. Parents and nurses assessed
      infants' pain response using a visual analog scale (VAS). Local adverse events
      (ie, erythema, blanching) at the application site were recorded. Nurses were
      asked to provide written responses regarding their willingness to incorporate
      local anesthetics in clinical practice and barriers to their use. RESULTS: From
      July 2003 to December 2004, 175 families were approached for participation in the
      study; 52 declined consent and 13 were not randomized. One hundred ten neonates
      were enrolled and evenly randomized to each group. Baseline characteristics were
      similar in both groups. During i.m. injection, the mean (SD) percent facial
      grimacing score was 70% (30%) for the amethocaine group compared with 75% (34%)
      for the placebo group (P = 0.41). The mean (SD) for percent cry duration was 55%
      (34%) compared with 62% (38%), respectively (P = 0.34). The mean (SD) latency to
      cry was significantly longer in the amethocaine group compared with the placebo
      group (4.7 [4.5] vs 2.7 [2.3] seconds; P = 0.01). Parents' and nurses' VAS
      ratings for infant pain did not differ between groups. The incidence of adverse
      events did not differ between groups. Ninety-seven percent of nurses (89/92) said
      they would use the intervention. Fifty-seven percent of nurses (52/92) identified
      barriers to incorporation with the primary reason being time constraint (67%
      [35/52]). CONCLUSIONS: Topical amethocaine gel 4% was ineffective in reducing
      pain on i.m. injection of vitamin K in these full-term neonates. Treatment was
      generally well tolerated and nurses concluded that, given the choice, they would
      use a topical anesthetic.

PMID- 18343254
TI  - Open-label, prospective, randomized comparison of propofol and sevoflurane for
      laryngeal mask anesthesia for magnetic resonance imaging in pediatric patients.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) for pediatric patients often
      requires deep sedation or anesthesia because they must remain completely immobile
      for a relatively long period to obtain high-quality images. OBJECTIVE: The aim of
      this study was to compare the effectiveness of propofol i.v. or inhalation of
      sevoflurane anesthesia with the laryngeal mask airway (LMA) for children
      undergoing MRI. METHODS: Children aged 2 to 6 years with American Society of
      Anesthesiologists' physical status of I to II who were scheduled for MRI were
      enrolled in this study and randomly divided into 2 groups. The propofol group was
      administered propofol 4 mg/kg i.v. followed by infusion of 150 microg/kg x min(
      1). Patients in the sevoflurane group were induced with sevoflurane 8% by face
      mask and maintained with an air/oxygen mixture followed by sevoflurane 1.5%. Data
      recorded included age, weight, scan time, LMA insertion, removal, and recovery
      times, hemodynamic parameters, complications, pediatric anesthesia emergence
      delirium (PAED) scale score, child movement, and MRI interruption. A higher PAED
      score indicated a higher level of delirium. RESULTS: Eighty-eight children were
      enrolled and randomized to treatment. Nine children were excluded from analysis
      due to protocol violations. After completion of the study, there were 37 children
      in the propofol group (male/female, 18/19; mean [SD] age, 42.1 months; weight,
      15.2 [4.9] kg; scan time, 20.5 [4.6] min) and 42 in the sevoflurane group
      (male/female, 15/27; mean [SD] age, 44.4 [26.1] months; weight, 15.1 [5.2] kg;
      scan time, 20.6 [4.8] min). No significant differences were found between the
      study groups with regard to age, weight, scan time, and hemodynamic parameters at
      baseline and during the study period. Mean LMA insertion, removal, and recovery
      times were significantly longer in the propofol group (4.8, 5.2, and 8.8 minutes,
      respectively) than in the sevoflurane group (3.3, 2.5, and 3.9 minutes,
      respectively) (P < 0.05). The mean PAED score in the propofol group was
      significantly lower than that in the sevoflurane group (mean [SD], 6.1 [4.0] vs
      10.5 [3.7]; P < 0.05). The percentage of MRI interruption in the propofol group
      was significantly higher than that in the sevoflurane group (4 [11%] vs 0,
      respectively; P < 0.05). No episodes of hypotension or bradycardia occurred
      during the study, and alterations in the propofol infusion rate or sevoflurane
      concentration were not necessary. One child vomited in the sevoflurane group
      during the postoperative period. CONCLUSIONS: This small study found that
      sevoflurane, at the doses used in this study, provided shorter induction and
      faster recovery times than i.v. propofol for LMA anesthesia in these selected
      children undergoing MRI. The percentage of MRI interruption in the propofol group
      was significantly higher than that in the sevoflurane group. Sevoflurane was
      associated with a significantly higher score on the PAED scale, indicating
      greater emergence delirium.

PMID- 18343255
TI  - Donepezil use in children and adolescents with tics and attention
      deficit/hyperactivity disorder: an 18-week, single-center, dose-escalating,
      prospective, open-label study.
AB  - BACKGROUND: Striatal cholinergic dysfunction may be important in tics and
      attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: The purpose of this
      study was to determine the safety profile of donepezil and whether it improves
      chronic tics in young patients with comorbid ADHD. METHODS: This 18-week (14
      weeks of open treatment followed by a 4-week washout period), single-center, dose
      escalating, prospective, open-label trial was conducted in patients aged 7 to 17
      years with tics, including chronic motor or vocal tics and Tourette's syndrome,
      and ADHD. Patients were treated with once-daily oral donepezil doses of 2.5 mg
      for 2 weeks, 5 mg for the next 6 weeks, and 10 mg for the last 6 weeks, followed
      by a 4-week washout period. Patients were evaluated using the Children's Global
      Assessment Scale; the Yale Global Tic Severity Scale (YGTSS); the Revised
      Conners' Parent Rating Scale; the Symbol and Digit Wisconsin Card Sorting Test;
      the Stroop black/white, color, and interference tests; the Rey Complex Figure
      Test; and the Children's Yale-Brown Obsessive Compulsive Scale at 4 visits:
      baseline, week 8 (5-mg dose), week 14 (10-mg dose), and week 18 (washout).
      RESULTS: Seventeen males and 3 females (mean [SD] age, 11.3 [1.9] years [range, 8
      14 years]; tic duration, 5.3 [1.9] years; ADHD duration, 6.5 [1.7] years) were
      included in this study. Tics were significantly reduced at the 10-mg (week-14)
      donepezil visit compared with the baseline and washout visits based on the total
      mean (SD) tic score of the YGTSS (18.6 [9.3] vs 12.2 [11.0]; P = 0.006). Fifty
      percent of patients withdrew and 65% experienced adverse events. CONCLUSIONS:
      These preliminary results suggest that donepezil significantly reduced tics in
      these children and adolescents with comorbid ADHD who completed the study. No
      significant improvement in the symptoms of comorbid ADHD was found with the use
      of donepezil 10 mg. Donepezil 5 and 10 mg were not well tolerated in these
      children and adolescents.

PMID- 18343256
TI  - Alzheimer's disease: the specter of fragmented policy and financing.

PMID- 18343257
TI  - Cardiovascular outcomes among patients newly initiating atorvastatin or
      simvastatin therapy: a large database analysis of managed care plans in the
      United States.
AB  - BACKGROUND: While the results of randomized clinical trials have indicated that
      statins improve outcomes in patients without cardiovascular disease (CVD), it
      remains uncertain whether there are differences in efficacy between statins,
      particularly in clinical practice, where the public health implications could be
      substantial. OBJECTIVE: We assessed cardiovascular (CV) outcomes among primary
      prevention patients newly initiating therapy with atorvastatin or simvastatin.
      METHODS: Using claims data from 92 US managed care plans, we identified new
      statin users without CVD who initiated atorvastatin (10 or 20 mg) or simvastatin
      (20 or 40 mg) from January 2003 to September 2005 and were continuously enrolled
      in a covered plan for > or = 12 months before and > or = 1 month after the
      initiation of statin therapy. The main outcome was the time to the first CV event
      (hospitalization related to myocardial infarction, angina, or coronary artery
      disease; stroke; amaurosis fugax; transient ischemic attack; peripheral or
      central nervous system vascular disease; or revascularization). Persistence with
      treatment was calculated in terms of the number of days during follow-up that a
      patient remained on statin treatment, starting from the date of the first
      prescription fill to the end of the study or the date at which therapy was
      discontinued. RESULTS: A total of 168,973 patients initiating atorvastatin (mean
      dose, 13.5 mg) and 50,658 patients initiating simvastatin (mean dose, 28.5 mg)
      were followed for a median of 1.5 years. Atorvastatin patients were significantly
      more persistent with treatment than simvastatin patients (median treatment
      duration, 158 vs 124 days, respectively; P < 0.001). After adjustment for age,
      sex, type of health plan, payer type, geographic region, calendar year of statin
      initiation, physician specialty, comorbidities, concomitant therapies, and total
      direct health care costs in the year before statin initiation, use of
      atorvastatin was associated with significantly fewer CV events compared with use
      of simvastatin (hazard ratio = 0.88; 95% CI, 0.83-0.93; P < 0.001). CONCLUSIONS:
      In these patients without CVD, atorvastatin 10 or 20 mg was associated with a
      significantly lower risk of CV events compared with simvastatin 20 or 40 mg.
      Further studies are required to determine whether differences in persistence,
      achieved low-density lipoprotein cholesterol levels, or other factors contribute
      to these differences in outcomes.

PMID- 18343258
TI  - Use of darbepoetin alfa and epoetin alfa in clinical practice in patients with
      cancer-related anemia.
AB  - BACKGROUND: Patients with cancer may receive erythropoiesis-stimulating agents
      (ESAs), including darbepoetin alfa (DA) or epoetin alfa (EA), to treat cancer
      related anemia (CRA). DA and EA differ, however, with respect to their assumed
      duration of effect and thus their approved frequency of dosing, complicating
      direct comparison of their doses and costs. OBJECTIVE: The objective of this
      study was to examine, from the perspective of a third-party payer, patterns of
      use and costs of DA and EA in patients with CRA, using episode-based methodology
      to account for differences in assumed duration of effect and frequency of dosing
      with these products. METHODS: Using a large US health insurance claims database,
      we identified all patients with cancer who received ESAs between January 1, 2005,
      and June 30, 2005 (study period). For each such patient, we identified all unique
      episodes of care (EOCs) with DA or EA, and then compared mean weekly dose and
      cost of ESA therapy within these EOCs, which were calculated using the ratio of
      total dose received and total cost of ESA therapy, respectively, to total EOC
      duration; only the first EOC for each patient was considered. EOCs were assumed
      to begin on the date of first ESA administration within the study period, and end
      on the date of final ESA administration (within the episode) plus an assumed
      duration of effect based on the ESA received and corresponding dose. We also
      estimated the ratio of mean weekly dose of EA (in units) to mean weekly dose of
      DA (in micrograms) (EA/DA weekly dose ratio). Multivariate regression was used to
      control for differences in baseline characteristics of EA and DA patients.
      RESULTS: We identified a total of 1226 patients with complete EOCs with ESAs (EA,
      381; DA, 845). DA patients were more likely to have had evidence of receipt of
      chemotherapy (54% vs 47% for EA; P = 0.02); they also had more comorbidities
      (mean Charlson comorbidity scores, 4.3 and 3.9, respectively; P < 0.01).
      Estimated mean (95% CI) weekly dose within EOCs was 97 microg (94-99) for DA, and
      43,184 U (40,181-46,589) for EA; EA/DA weekly dose ratio was 445:1. Adjustment
      for differences in patient characteristics yielded a slightly lower ratio
      (403:1). Results were sensitive to the exclusion of EOCs consisting of a single
      administration of ESA therapy and/or the addition of an assumed duration of
      effect to the final ESA dose administered. CONCLUSIONS: Cost comparisons of DA
      and EA are sensitive to the assumed duration of effect added to the final dose of
      ESA therapy, especially for EOCs with relatively few administrations.

PMID- 18343259
TI  - The effects of direct-to-consumer advertising of statins on the attainment of low
      density lipoprotein cholesterol goals.

PMID- 18343261
TI  - A review of infliximab use in ulcerative colitis.
AB  - BACKGROUND: Infliximab is a chimeric immunoglobulin G1kappa monoclonal antibody
      that binds with high affinity and specificity to the soluble form of tumor
      necrosis factor (TNF)-alpha, preventing it from binding to cellular receptors.
      Infliximab also binds to membranebound TNF-alpha found on inflammatory cell
      surfaces, inducing apoptosis. Currently, infliximab is used for the induction and
      maintenance of remission in Crohn's disease (CD), with documented success.
      Infliximab's efficacy in the treatment of ulcerative colitis (UC) is now being
      investigated due to the similarities in the pathophysiology of CD and UC.
      OBJECTIVE: The aim of this study was to review and evaluate the current
      literature of infliximab use in steroid-refractory UC to assess its role in
      treatment. METHODS: A search of MEDLINE was conducted (1950-November 2007). Key
      terms included, but were not limited to, infliximab, inflammatory bowel disease,
      ulcerative colitis, cost, and quality of life. Studies included for review were
      limited to English-language, full-text, randomized, double-blind, placebo
      controlled trials. Clinical trials were reviewed and summarized. RESULTS: Four
      controlled clinical trials of infliximab in the treatment of steroid-refractory
      UC were found and assessed. In a double-blind, randomized, controlled trial in 43
      patients with moderately severe, glucocorticoid-resistant UC, infliximab and
      placebo were not significantly different with respect to clinical and
      sigmoidoscopic remission or quality of life 2 and 6 weeks after infliximab
      treatment. In a multicenter, randomized, double-blind, placebo-controlled study
      in 45 patients with moderately severe to severe glucocorticoid-resistant UC,
      infliximab was associated with a significantly reduced need for colectomy
      compared with placebo (29% vs 67%; P=0.017). The Active Ulcerative Colitis Trials
      (ACT) 1 and 2 together included 728 patients with moderate to severe
      glucocorticoid-resistant UC. The primary outcome, the rate of clinical response
      at 8 weeks, was significantly higher with infliximab compared with placebo (5
      mg/kg: ACT 1, 69.4%, ACT 2, 64.5%; 10 mg/kg: ACT 1, 61.5%, ACT 2, 69.2%; placebo:
      ACT 1, 37.2%;, ACT 2, 29.3%; all, P < 0.001 vs placebo). Based on the data from
      ACT 1 and 2, infliximab was associated with improved health-related quality-of
      life (HRQOL) scores based on the Inflammatory Bowel Disease Questionnaire and the
      36-item Short Form Health Survey. CONCLUSIONS: Current data suggest that
      infliximab is an effective alternative treatment option for patients with
      moderate to severe UC with an inadequate response to conventional glucocorticoid
      treatment. Further trials are needed to assess infliximab's impact on the
      treatment and progression of UC, the HRQL of patients with UC, and the economic
      impact on the health care system.

PMID- 18343262
TI  - Paliperidone extended-release tablets for the acute and maintenance treatment of
      schizophrenia.
AB  - BACKGROUND: Paliperidone, which is available in extended-release (ER) tablets,
      was approved by the US Food and Drug Administration in 2007 for the acute and
      maintenance treatment of schizophrenia. It is the seventh second-generation
      antipsychotic (SGA) to be introduced to the US market. Paliperidone is the major
      active metabolite of risperidone, an established anti-psychotic agent. OBJECTIVE:
      This article reviews the available literature on the pharmacodynamics,
      pharmacokinetics, clinical efficacy, and tolerability of paliperidone. METHODS: A
      comprehensive search of MEDLINE using the terms paliperidone, 9-hydroxy
      risperidone, and Invega was performed for the years 1950 through December 2007.
      Articles that discussed the efficacy and tolerability of 9-hydroxy-risperidone
      formed as a metabolite of risperidone were excluded; all others were included.
      Abstracts and posters presented at recent national and international scientific
      meetings were also included in the review. RESULTS: At therapeutic doses (3-12
      mg), paliperidone ER follows linear pharmacokinetics. Like that of its parent
      drug, paliperidone's mechanism of action is thought to be through antagonistic
      actions at dopamine D(2) and serotonin-2A receptors. In vivo studies suggest that
      the cytochrome P450 enzyme system plays a minimal role in paliperidone
      metabolism, with none of the metabolites accounting for >10% of a dose. The
      majority (59%) of paliperidone is eliminated through the kidneys as unchanged
      drug. The results of three 6-week, randomized, double-blind, parallel-group
      trials indicated the efficacy of paliperidone ER compared with placebo in the
      treatment of acute exacerbations of schizophrenia, with response rates ranging
      from 39.8% to 61.0% for paliperidone ER, compared with 18.3% to 34.0% for
      placebo. During a 52-week, double-blind, relapse-prevention trial, the time to
      25% of patients experiencing a recurrence was 83 days for paliperidone ER,
      compared with 23 days for placebo. The proportions of patients in the 6-week
      trials who reported at least 1 extrapyramidal symptom-related adverse event were
      13%, 10%, 25%, 26%, and 24% for paliperidone ER 3, 6, 9, 12, and 15 mg/d,
      respectively; the pooled incidence rate was not statistically different from that
      with placebo (11%). Headache and insomnia were the most common adverse events in
      patients treated with paliperidone ER in the 6-week trials (pooled data: 11%-18%
      and 4%-14%, respectively). In the relapse-prevention trial, the incidence of
      prolactin-related adverse events was 4% for paliperidone ER and 0% for placebo.
      CONCLUSIONS: Current evidence supports the efficacy and tolerability of
      paliperidone ER in the acute and long-term treatment of schizophrenia.
      Randomized, head-to-head comparisons with other SGAs, particularly risperidone,
      are needed to define the role of paliperidone ER in the treatment of
      schizophrenia.

PMID- 18343263
TI  - Antiplatelet profiles of the fixed-dose combination of extended-release
      dipyridamole and low-dose aspirin compared with clopidogrel with or without
      aspirin in patients with type 2 diabetes and a history of transient ischemic
      attack: a randomized, single-blind, 30-day trial.
AB  - BACKGROUND: Clopidogrel, aspirin (ASA), and the fixed-dose combination of
      extended-release dipyridamole and ASA (ER-DP+ASA) are widely used in post-stroke
      regimens. OBJECTIVE: This study compared serial changes in multiple biomarkers of
      platelet activation with ER-DP+ASA and clopidogrel with or without ASA in
      patients with type 2 diabetes mellitus and a history of transient ischemic attack
      (TIA). METHODS: This was a randomized, single-blind pilot study conducted at an
      outpatient center in the United States. Eligible patients were aged 40 years and
      had a diagnosis of type 2 diabetes and a history of TIA. Patients were allocated
      to receive ER-DP+ASA 200/25 mg BID, clopidogrel 75 mg/d, or clopidogrel 75 mg/d
      plus ASA 81 mg/d. Multiple platelet bio-markers were assessed at baseline, day
      15, and day 30 using aggregometry, cartridge-based platelet function analyzers,
      and flow cytometry. The primary end point was the change in platelet receptor
      expression after 30 days of therapy. Compliance and tolerability were monitored
      by measuring plasma dipyridamole levels and recording all episodes of headache
      and vomiting. RESULTS: The study enrolled 60 consecutive patients (20 per
      treatment arm), all of whom completed the study. There were no significant
      differences between treatment arms, although the ER-DP+ASA group had a
      numerically greater mean age, higher proportion of men, and a greater prevalence
      of vascular disease and smoking compared with the other groups. There were no
      deaths or serious adverse events during the study, including symptoms
      attributable to cerebral ischemia, worsening of diabetes, or cerebral or systemic
      bleeding. Three patients in the ER-DP+ASA group and 1 in the clopidogrel plus ASA
      group reported headache during the first several days of therapy; 1 patient in
      the clopidogrel monotherapy group experienced transitory nausea and vomiting. ER
      DP+ASA was associated with a significantly delayed (day 30) reduction in
      expression of glyco-protein (GP) Ilb/IIIa activity (P = 0.02), platelet
      endothelial cell adhesion molecule 1 (PECAM-1) (P = 0.03), GP Ib (P = 0.001),
      vitronectin (P = 0.001), P-selectin (P = 0.001), lysosome-associated membrane
      protein 1 (P = 0.001), and cluster of differentiation 40 ligand (P = 0.01), as
      well as significant inhibition of the intact (P = 0.01) and cleaved (P = 0.01)
      epitopes of protease-activated receptor 1. Clopidogrel monotherapy, on the other
      hand, was associated with significant inhibition of adenosine diphosphate-induced
      platelet aggregation (P = 0.001), closure-time prolongation (P = 0.01), and
      reduction in measurements on the rapid platelet function assay-ASA at day 15 (P =
      0.001). Expression of PECAM-1 (P = 0.03) and GP IIb/IIIa activity (P = 0.01) was
      reduced at day 15 in clopidogrel-treated patients. The addition of ASA to
      clopidogrel was associated with significant inhibition of collagen-induced
      platelet aggregation (P = 0.001) and diminished formation of platelet-monocyte
      microparticles at days 15 (P = 0.02) and 30 (P = 0.03). CONCLUSIONS: In these
      patients with type 2 diabetes and a history of TIA, patterns of platelet
      inhibition differed significantly according to whether treatment was with ER
      DP+ASA or clopidogrel with or without ASA. The antiplatelet activity of
      clopidogrel was more potent and occurred earlier (15 days), whereas ER-DP+ASA was
      associated with moderate downregulation of multiple activation-dependent platelet
      receptors that occurred later (30 days).

PMID- 18343264
TI  - Effect of levetiracetam on cardiac repolarization in healthy subjects: a single
      dose, randomized, placebo- and active-controlled, four-way crossover study.
AB  - BACKGROUND: Nonantiarrhythmic drugs may have the potential to prolong the QT
      interval, leading to potentially fatal ventricular tachycardias, including
      torsades de pointes. OBJECTIVE: This study evaluated the potential of the newer
      generation, multiple-action antiepileptic drug levetiracetam, which binds to the
      synaptic vesicle protein SV2A, to affect cardiac repolarization, as detected by
      prolongation of the QT/corrected QT (QTc) interval. METHODS: This was a single
      dose, randomized, placebo- and active-controlled, 4-way crossover study in
      healthy subjects. Subjects were randomly allocated to 1 of 4 different
      administration sequences. Each sequence included 3 double-blind treatments
      (levetirace-tam 1000 mg, levetiracetam 5000 mg, and placebo) and 1 open-label
      treatment (moxifloxacin 400 mg). Triplicate electrocardiograms (ECGs) were
      obtained at baseline and at various time points over 24 hours after each
      treatment using continuous Holter monitoring. ECGs were read centrally in a
      blinded manner. Blood samples for the determination of plasma concentrations of
      levetiracetam and moxifloxacin were collected before dosing and at 0.5, 1, 1.5,
      2, 4, 6, 12, and 24 hours after dosing, within 5 minutes after the ECG
      recordings. The QT interval was corrected for heart rate using a sex- and study
      specific correction (QTc(ss)) as the primary outcome measure and Fridericia's
      correction (QTc(F))as a secondary outcome measure. The primary analysis was
      performed on the time-matched, baseline-subtracted QTc(ss) (DeltaQTc(ss)). The
      maximum DeltaQTc(ss) difference between each active treatment and placebo
      (DeltaDeltaTc(ss)) was derived from a mixed-effect analysis of variance. Clinical
      laboratory tests, standard 12-lead ECGs, and vital signs were monitored at
      regular intervals. Spontaneously reported adverse events were recorded throughout
      the study. RESULTS: Fifty-two healthy, nonsmoking subjects (26 men, 26 women; 37
      white, 9 black, 3 Hispanic, and 3 Asian/Pacific Islander) with a mean (SD) age of
      28.4 (7.5) years (range, 18-45 years) and a mean weight of 71.5 (12.6) kg (range,
      49-103 kg) participated in the study. Levetiracetam did not significantly prolong
      the QTc(ss). The upper bound of the 1-sided 95% CI for the maximum
      DeltaDeltaTc(ss) was 8.0 milliseconds for levetiracetam 1000 mg and 8.1
      milliseconds for levetiracetam 5000 mg, with mean estimates of 4.0 and 4.1
      milliseconds, respectively; similar results were obtained for the maximum
      DeltaDeltaQTc(F). Moxifloxacin significantly prolonged the QTc(ss), with a lower
      bound of the 1-sided 95% CI for the maximum DeltaDeltaQTc(ss) of 3.7 milliseconds
      and a mean estimate of 7.7 milliseconds. There was no statistically significant
      relationship between measured DeltaQTc(ss) and the levetiracetam plasma
      concentration, whereas a significant linear relationship was observed between
      measured DeltaQTc(ss) and the moxifloxacin plasma concentration (slope estimate:
      4.4 milliseconds/[microg/mL]); 95% CI, 3.2-5.7; P < 0.001). No unexpected safety
      concerns arose based on reported adverse events, clinical laboratory evaluations,
      physical examinations, vital signs, or ECG monitoring during the course of the
      study. CONCLUSION: This randomized, placebo- and active-controlled study in
      healthy adult subjects found no clinically relevant changes in the QTc interval
      after a single levetiracetam dose of 1000 or 5000 mg.

PMID- 18343265
TI  - Preferences of adult patients with allergic rhinitis for the sensory attributes
      of fluticasone furoate versus fluticasone propionate nasal sprays: a randomized,
      multicenter, double-blind, single-dose, crossover study.
AB  - BACKGROUND: Product attributes influence patient preference for intranasal
      corticosteroid therapy in allergic rhinitis (AR). OBJECTIVE: The aim of the study
      was to compare the product sensory attributes and patient preferences of
      fluticasone furoate (FF) and fluticasone propionate (FP) nasal sprays in patients
      with symptomatic perennial and/or seasonal AR. METHODS: This randomized,
      multicenter, double-blind, single-dose, crossover study enrolled 127 patients
      with a diagnosis of AR as determined by respiratory symptoms and a positive skin
      test to perennial and/or seasonal allergens within 12 months prior to the study.
      Patients could not use FF or FP within 4 weeks prior to the start of the study.
      Patients were randomized 1:1 to receive FF (110 microg) followed by FP (200
      microg) or FP followed by FF. A 10-minute washout period occurred before
      crossover dosing. Following each treatment, patient-rated sensory attributes were
      assessed immediately and 2 minutes after treatment on 2 questionnaires using a 7
      point Likert scale (scored from 0-6) rating odor, taste, aftertaste, drip down
      the throat, urge to sneeze, soothing feeling, irritation, and nose runoff. At the
      end of the crossover dosing and after completion of the attributes
      questionnaires, preference for individual attributes of FF or FP nasal spray and
      overall patient preference were evaluated in a third questionnaire that asked
      "Based on these attributes, which product did you prefer overall?" Additionally,
      a follow-up phone call was conducted 24 hours after the study to assess any
      adverse events following study treatment. RESULTS: Patients (mean age, 39.7
      years; 80% white; 65% women) preferred FF nasal spray over FP nasal spray overall
      (60% vs 33%; P = 0.003) and based on the individual attributes of odor (64% vs
      29%; P < 0.001), taste (47% vs 21%; P < 0.001), aftertaste (44% vs 22%; P =
      0.002), drip down the throat (43% vs 27%; P = 0.037), and nose runoff (49% vs
      19%; P < 0.001). Patient ratings favored FF versus FP (median differences, P <
      0.001) with respect to odor, taste, dripping down the throat, and nose runoff,
      both immediately and 2 minutes after dosing, but there were no significant
      differences with respect to whether the medication felt soothing, caused nasal
      irritation, or made patients sneeze. Fifty-two percent (63/121) of patients
      replied that they were very likely to comply with FF treatment versus FP
      treatment (38% [45/120]; P = 0.02) if the medications were prescribed. Three
      patients (2%) reported adverse events (dizziness, headache, nasal congestion)
      during treatment with FF. CONCLUSION: In this study of adult AR patients, the
      sensory attributes of FF were preferred over those of FP following single-dose
      administration.

PMID- 18343266
TI  - Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing
      pain on injection of propofol in Japanese adult surgical patients: a prospective,
      randomized, double-blind, parallel-group, placebo-controlled study.
AB  - BACKGROUND: Pain on injection is a recognized adverse event (AE) of propofol
      administration for the induction of general anesthesia. Pretreatment with
      lidocaine, metoclopramide, or flurbiprofen axetil has been reported to be
      effective in reducing propofol-induced pain. However, no studies comparing the
      efficacy of these 3 drugs for preventing pain on injection of propofol have been
      identified. OBJECTIVE: The aim of this study was to compare the efficacy of
      lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection
      of propofol in Japanese adult surgical patients. METHODS: This prospective,
      randomized, double-blind, parallel-group, placebo-controlled study was conducted
      at the Department of Anesthesiology, Ushiku Aiwa General Hospital, Ibaraki,
      Japan. Japanese patients scheduled to undergo elective surgery were eligible for
      inclusion in the study. Patients were randomized into 4 groups to receive IV
      lidocaine 40 mg, metoclopramide 10 mg, flurbiprofen axetil 50 mg, or placebo
      (saline), preceded by venous occlusion with a rubber tourniquet for 2 minutes,
      and followed by the administration of propofol 0.5 mg/kg into the largest vein of
      the hand through a 20-gauge IV cannula. Immediately after the administration of
      propofol, an investigator blinded to treatment interviewed each patient on
      injection-site pain. Responses were scored on a 4-point verbal rating scale (0 =
      none, 1 = mild pain, 2 = moderate pain, and 3 = severe pain). Incidence and
      intensity of pain (as assessed by mean pain scores) were determined in each of
      the 4 study groups. AEs at the injection site (eg, pain, edema, wheal,
      inflammation), extrapyramidal disturbance, and symptoms or signs associated with
      gastrointestinal (GI) ulceration were assessed by the study investigator for 24
      hours following surgery using spontaneous reporting and patient interview.
      RESULTS: A total of 100 patients (54 women, 46 men) aged 22 to 65 years were
      enrolled in the study. The patients' mean (SD) age was 42 (12) years. Their mean
      (SD) height was 161 (8) cm and their mean (SD) weight was 59 (9) kg. Each
      treatment group comprised 25 patients. There were no significant differences in
      demographic characteristics between treatment groups. The overall incidence of
      propofol-induced pain was 24% (6/25 patients) with lidocaine (P = 0.001), 28%
      (7/25 patients) with metoclopramide (P = 0.001), and 36% (9/25 patients) with
      flurbiprofen axetil (P = 0.001), compared with placebo (92%, [23/25 patients]).
      The median pain score was less in patients who had received lidocaine (0),
      metoclopramide (0), or flurbiprofen axetil (0) than in those who received placebo
      (2) (all, P = 0.001). The incidence and severity of such pain were not
      significantly different between the lidocaine-, metoclopramide-, and flurbiprofen
      axetil-treated groups. There were no reported injection-site AEs, extrapyramidal
      disturbance, or symptoms or signs associated with GI ulceration observed.
      CONCLUSIONS: In this study of Japanese adult surgical patients, lidocaine 40 mg,
      metoclopramide 10 mg, and flurbiprofen axetil 50 mg, preceded by venous occlusion
      for 2 minutes, were effective in reducing pain during the injection of propofol.
      The analgesic efficacy of these 3 drugs was comparable for minimizing such pain.

PMID- 18343267
TI  - A retrospective analysis of the fasting plasma glucose and glycosylated
      hemoglobin and pharmacotherapy change patterns among type 2 diabetes mellitus
      patients.
AB  - OBJECTIVE: The aim of this study was to describe glycemic control levels (fasting
      plasma glucose [FPG] and glycosylated hemoglobin [HbA(1c)]) and pharma-cotherapy
      change patterns among a cohort of patients with type 2 diabetes mellitus (T2DM)
      receiving various antidiabetic agents. METHODS: This study, a retrospective
      analysis conducted from a large electronic medical record database, identified
      T2DM patients with > or =1 prescription for metformin, sulfonylureas, or
      thiazolidinediones from January 23, 1997, through March 15, 2006. The database
      contained medical and clinical records of patients-including diagnoses,
      medications, laboratory results, and physician orders-linked through encrypted
      patient identifiers. This study calculated the mean and median FPG and HbA(1c)
      values (performed within 30 days before or after a pharmacotherapy change) and
      the percentage of patients with values above those recommended by the American
      Diabetes Association (ADA) and the American College of Endocrinology
      (ACE)/American Association of Clinical Endocrinologists(AACE). RESULTS: The study
      included a total of 7769 T2DM patients (3942 female/3827 male; 56.9% were aged 50
      69 years). For patients with no pharmacotherapy change, most did not achieve the
      ADA recommendations for FPG (56.4% [1917/3398]) or HbA(1c) (48.6% [952/1958]) or
      the ACE/AACE recommendations forFPG (79.4% [2698/3398]) or HbA(1c) (65.4%
      [1281/1958]). These patients' mean FPG level was 151.9 mg/ dL (95% CI, 150.0
      153.9 mg/dL) and their mean HbA(1c) value was 7.51% (95% CI, 7.43%-7.60%). For
      patients with a pharmacotherapy change, the mean FPG level was 191.1 mg/dL (95%
      CI, 186.7-195.4 mg/dL) and the mean HbA(1c) value was 8.85% (95% CI, 8.70%
      9.00%). Similar to those with no pharmacotherapy change, a large percentage of
      patients with a pharmacotherapy change did not achieve the ADA recommendations
      for FPG (77.7% [1107/1425]) or HbA(1c) (76.2% [753/988]) or the ACE/AACE
      recommendations for FPG (90.1% [1284/1425]) or HbA(1c) (88.5% [874/988]).
      CONCLUSION: Despite the proven benefits of maintaining glycemic control and its
      impact on reducing long-term risk of diabetes complications, these results
      indicate that the mean FPG and HbA(1c) values for a large percentage of diabetic
      patients included in this study remained above those recommended by the ADA and
      the ACE/AACE.

PMID- 18343268
TI  - Management of mixed dyslipidemia in patients with or at risk for cardiovascular
      disease: a role for combination fibrate therapy.
AB  - BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) is the primary
      focus of the management of dyslipidemia in patients with or at risk for
      cardiovascular disease. However, use of a statin alone may be insufficient for
      the treatment of mixed dyslipidemia, which is characterized by low levels of high
      density lipoprotein cholesterol and elevated levels of triglycerides, with or
      without elevated levels of LDL-C. OBJECTIVE: This report reviews the evidence for
      the efficacy and tolerability of different combination treatments for the
      management of mixed dyslipidemia, as supported by clinical-trial data and
      recommended by national guidelines. METHODS: Using the terms lipid-modifying
      therapy, combination therapy, combination statin-fibrate therapy, and mixed
      dyslipidemia, a search of PubMed was conducted (completed in April 2007, updated
      to October 2007) to identify English-language publications and pertinent studies
      of fibrate combination therapy in patients with mixed dyslipidemia, including
      those with diabetes or the metabolic syndrome. RESULTS: National guidelines
      recommend the addition of either niacin (nicotinic acid) or a fibrate to statin
      therapy in patients with mixed dyslipidemia to achieve better overall lipid
      control. Fibrates do not have detrimental effects on uric acid levels or glycemic
      control in patients with diabetes or the metabolic syndrome. Based on data from
      the US Food and Drug Administration Adverse Event Reporting System indicating
      that gemfibrozil plus a statin was associated with a 15-fold higher risk of
      rhabdomyolysis than fenofibrate plus a statin, fenofibrate may be the fi-brate of
      choice for use in combination with a statin. As reported by the Fenofibrate
      Intervention and Event Lowering in Diabetes study, fenofibrate treatment has also
      been associated with microvascular benefits in patients with type 2 diabetes,
      which is consistent with preliminary evidence from the Diabetes Atherosclerosis
      Intervention Study. CONCLUSION: The addition of fenofibrate to statin therapy may
      be a useful strategy for the management of mixed dyslipidemia in patients with or
      at risk for cardiovascular disease.

PMID- 18343269
TI  - Observations of nonadherence to recombinant human growth hormone therapy in
      clinical practice.
AB  - BACKGROUND: The effectiveness of all prescribed treatments is contingent on
      patient adherence. The reported levels of adherence to recombinant human growth
      hormone (r-hGH) therapy are highly variable, but it has been suggested that
      nonadherence might be as high as 36% to 49%. OBJECTIVES: This commentary
      discusses the factors that affect long-term adherence to injection treatment, of
      which r-hGH therapy is a particular challenge. It also explores potential
      strategies to improve adherence to injection treatments in clinical practice.
      METHODS: The opinion of the authors was validated and supported by published
      literature. A PubMed literature search was conducted in November 2006,
      identifying English-language articles containing key terms growth hormone,
      adherence, and compliance. RESULTS: This study found that factors associated with
      poor adherence to injection treatments include patients' lack of understanding of
      their disease, patient age, chronicity of the disease, complex treatment
      regimens, and insufficient information on the implications of nonadherence.
      Strengthening the patient-physician relationship by providing the patient with a
      clear understanding of his/her disease and the benefits of adherence, making
      improvements in injection devices, and eliminating subjective illness concepts,
      might increase adherence to SC injection treatments, thereby reducing increasing
      health care costs associated with nonadherence. CONCLUSIONS: Poor adherence to r
      hGH therapy has a dual effect, in that it leads to reduced efficacy out-comes and
      increased health care costs. Implementing strategies to improve adherence with
      injection treatment might be of particular clinical benefit to patients
      undergoing r-hGH therapy.

PMID- 18343270
TI  - Adefovir and lamivudine in combination compared with adefovir monotherapy in
      HBeAg-negative adults with chronic hepatitis B virus infection and clinical or
      virologic resistance to lamivudine: a retrospective, multicenter, nonrandomized,
      open-label study.
AB  - OBJECTIVES: The aim of this study was to assess the therapeutic effectiveness of
      adefovir dipivoxil (ADV), administered in combination with lamivudine (LAM) or as
      monotherapy, and the rate of resistance to ADV, in hepatitis B e antigen (HBeAg)
      negative adult patients with chronic hepatitis B virus (HBV) infection and
      clinical or virologic resistance to LAM. Furthermore, we evaluated in these
      selected patients the clinical co-variates associated with a sustained virologic
      response. METHODS: Data from adult outpatients aged >18 years with chronic HBV
      infection and clinical or virologic resistance to LAM were used in this
      retrospective, multicenter, nonrandomized, open-label study. Patients were
      selected if they received ADV 10 mg PO QD + LAM 100 mg QD PO or ADV 10 mg PO QD
      as monotherapy for 24 to 32 months between June 2003 and July 2006. End points
      were the proportions of patients who achieved virologic response (undetectable
      HBV-DNA [<3.3 log(10) copies/mL]) and biochemical response (normalization [<40
      IU/L] of alanine aminotransferase [ALT]), and the proportions in whom resistance
      to ADV (rebound serum HBV-DNA >1 log(10) copies/mL compared with on-treatment
      nadir, as confirmed on molecular analysis) was found. HBV-DNA and ALT levels were
      checked every month during the first 3 months of treatment and every 3 months
      thereafter until 28 months. Data from each center were stored in a centralized
      database and analyzed by a blinded independent investigator. RESULTS: Data from
      70 patients were included (48 men, 22 women; median age, 51 years; ADV + LAM, 36
      patients; ADV monotherapy, 34). The median duration of the pharmacologic
      treatment in the 2 groups of patients was 28 months (range, 24-32 months). By
      month 3, virologic response was achieved in 30 patients (83%) in the ADV + LAM
      group and in 26 patients (76%) in the ADV monotherapy group. At 12 months,
      virologic response was achieved in 5 additional patients in the ADV + LAM group
      and 2 additional patients in the ADV monotherapy group. Biochemical response was
      found to be time dependent: in the 2 groups, the rates of biochemical response
      were, respectively, 56% and 54% at month 3, 80% and 71% at month 6, and 96% and
      79% at month 12, persisting up to the end of the study period. The rates of
      clinical resistance to ADV were 3% with ADV + LAM and 18% with ADV monotherapy
      (with a 6% rate of resistance due to rtA181 mutation in the monotherapy group).
      Logistic regression analysis found that pre-treatment levels of HBV-DNA <5
      log(10) copies/mL, ALT levels >150 IU/L, an inflammation score >7, and a fibrosis
      score <2 were the strongest covariates independently associated with a sustained
      virologic response in both groups of patients. No adverse events were reported in
      any of the patients. CONCLUSION: ADV, administered in combination with LAM or as
      monotherapy, appeared to be effective in this small, selected group of HBeAg
      negative patients with clinical or virologic resistance to LAM, especially in
      those with low pretreatment HBV-DNA levels, high ALT levels, and low fibrosis
      scores.

PMID- 18343271
TI  - Practical management of cutaneous reactions to the methylphenidate transdermal
      system: recommendations from a dermatology expert panel consensus meeting.
AB  - BACKGROUND: Psychostimulants remain the most-used medications for attention
      deficit/hyperactivity disorder (ADHD). The methylphenidate transdermal system
      (MTS) is the first stimulant patch dosage formulation to be approved by the US
      Food and Drug Administration for the treatment of the symptoms of ADHD in
      children aged 6 to 12 years. The MTS patch is approved to be applied once daily
      to the hip and worn for 9 hours. While cutaneous reactions may occur with any
      formulation of medication, they are more likely with transdermal administration.
      OBJECTIVE: The purpose of this commentary was to describe the types of cutaneous
      reactions that have been reported with transdermal systems in general, review the
      cutaneous adverse events seen in clinical trials with the MTS specifically, and
      provide practical management suggestions for prevention and treatment of these
      potential cutaneous reactions. METHODS: In September 2007, a group of child
      psychiatrists, pediatricians, developmental pediatricians, and pediatric
      neurologists who treat ADHD and have had experience in their practices with MTS
      convened to discuss cutaneous reactions in relation to its use. Information
      collected from this meeting and from the clinical trials database of the sponsor
      was reviewed by a panel of 3 dermatologic clinical experts in contact dermatitis
      and 1 pediatric dermatologist. The panel's recommendations form the basis for
      this report. CONCLUSIONS: Mild to moderate erythema is a common cutaneous effect
      with MTS use, and is generally not a cause for discontinuation if seen in
      isolation. Irritant contact dermatitis is relatively common and can be reduced
      and treated by alternating patch application sites, moisturizing, gentle skin
      care, and application of topical corticosteroids at the previous patch sites if
      needed. Allergic contact dermatitis (ACD) and allergic contact urticaria are rare
      when MTS is worn as directed in the prescribing information. MTS should be
      discontinued if ACD is suspected.

PMID- 18343272
TI  - An invitation to the health policy debates.

PMID- 18343273
TI  - The impact of indirect (herd) protection on the cost-effectiveness of
      pneumococcal conjugate vaccine.
AB  - BACKGROUND: The heptavalent pneumococcal polysaccharide-protein conjugate vaccine
      (PCV7) confers protection against invasive pneumococcal disease (IPD) caused by
      serotypes that are responsible for substantial morbidity and mortality throughout
      the world. In 2000, the 7 serotypes covered by PCV7 accounted for 80% to 90% of
      serotypes isolated from the blood or cerebrospinal fluid of children aged <6
      years in the United States. A previous review of the literature spanning the
      years 1998 to 2005 pertaining to the incidence of IPD among nonimmunized
      individuals in countries with universal PCV7 immunization suggested an indirect
      protective effect (herd protection, or community immunity) after widespread
      vaccination. Consideration of indirect protection against IPD may enhance cost
      benefit evaluations of vaccination programs. OBJECTIVE: The objective of this
      analysis was to review the literature on cost-effectiveness analyses of PCV7
      vaccination to determine whether inclusion of the indirect effect in decision
      analysis models substantially affects the cost-effectiveness findings in favor of
      vaccination. METHODS: A literature review of cost-effectiveness analyses of PCV7
      vaccination was conducted using the DIMDI (Deutschen Institut fur Medizinische
      Dokumentation und Information) superbase, which comprises 12 databases, to
      identify articles published between January 2000 and October 2006 using the
      search terms 7-valent pneumococcal conjugate vaccine AND herd immunity/herd
      effect, and 7-valent pneumococcal conjugate vaccine AND cost-effectiveness, cost
      utility, or cost-benefit analyses. Monetary values were converted to euros and
      inflated to 2006 values, and events avoided were converted to rates per 100,000
      vaccinated to allow comparison across studies. The sensitivity analyses from the
      models that included indirect effects were examined. RESULTS: There was wide
      variability in the health-economic results of the 16 studies that met the
      inclusion criteria. In studies that did not include indirect effects, the
      adjusted cost per life-year gained ranged from cost saving to euro140,723 from
      the societal perspective and from euro56,724 to euro324,218 from the payer
      perspective. In the 4 studies that included indirect effects, a significant and
      consistent improvement was seen in the health-economic results in favor of
      vaccination with PCV7. No trends in variability across time or geographic region
      were observed. CONCLUSIONS: Indirect effects had a significant effect on cost
      effectiveness, as seen in the sensitivity analyses. Future models should include
      indirect effects in evaluating the cost-effectiveness of PCV7.

PMID- 18343274
TI  - Treatment failure rates and health care utilization and costs among patients with
      community-acquired pneumonia treated with levofloxacin or macrolides in an
      outpatient setting: a retrospective claims database analysis.
AB  - BACKGROUND: Macrolide antibiotics and fluoroquinolones are extensively used in
      the treatment of community-acquired pneumonia (CAP). OBJECTIVE: This analysis was
      conducted to compare treatment failure rates and health care utilization and cost
      outcomes among patients with CAP treated with levo-floxacin (500 or 750 mg) or
      macrolides (azithromycin, clarithromycin, or erythromycin) in an outpatient
      setting. METHODS: This was a retrospective analysis of claims data from a large
      US health plan. Patients were aged > or =18 years and had a primary diagnosis of
      CAP that was treated with oral levofloxacin or a macrolide in an outpatient
      setting (including physicians' offices, outpatient clinics, urgent care centers,
      and large ambulatory health centers). Patients were followed for 30 days after
      the index drug date to measure study outcomes. Multivariate regression analysis
      and a propensity score technique were used to compare rates of treatment failure
      and CAP-related health care utilization and costs. Two post hoc subgroup analyses
      were conducted in patients aged > or =50 and > or =65 years. RESULTS: Of the 7526
      patients meeting the inclusion criteria, 2968 (39.4%) were treated with
      levofloxacin and 4558 (60.6%) with a macrolide. Unadjusted rates of treatment
      failure were 21.1% and 22.7% in the levofloxacin and macrolide cohorts,
      respectively. After adjustment for demographic characteristics, baseline
      comorbidities, and severity of illness, levofloxacin recipients were
      significantly less likely to experience treatment failure than macrolide
      recipients (odds ratio [OR] = 0.84; 95% CI, 0.75-0.94, P = 0.003). The likelihood
      of treatment failure was significantly lower in levofloxacin recipients aged > or
      =50 years (OR = 0.79; 95% CI, 0.66-0.94; P = 0.007) and > or =65 years (OR =
      0.65; 95% CI, 0.43-1.00; P = 0.049) compared with the corresponding subgroups of
      macrolide recipients. The magnitude of this difference was greatest in the
      subgroup aged > or =65 years, which had a 35% reduced risk of treatment failure
      compared with the corresponding group of macrolide-treated patients. The rate of
      CAP-related emergency department visits was significantly lower among patients
      receiving levofloxa-cin (OR = 0.68; 95% CI, 0.51-0.91; P = 0.009); there were no
      differences in CAP-related hospitalizations or total CAP-related health care
      costs between levofloxa-cin and macrolide recipients. CONCLUSIONS: Multivariate
      adjusted rates of treatment failure in outpatients with CAP were significantly
      lower in those treated with levofloxacin relative to those treated with a
      macrolide. The lower rates of treatment failure with levofloxacin were
      consistently observed across all patients and in the subgroups aged > or =50 and
      > or =65 years. Rates of emergency department visits were also significantly
      lower among levofloxacin-treated patients, whereas overall CAP-related hospitali
      zations and costs did not differ significantly between the 2 treatment groups.

PMID- 18343275
TI  - Cost-effectiveness analysis of emtricitabine/tenofovir versus
      lamivudine/zidovudine, in combination with efavirenz, in antiretroviral-naive,
      HIV-1-infected patients.
AB  - OBJECTIVE: The aim of this study was to compare the cost per unit of
      effectiveness (successful treatment episode) of 2 highly active antiretroviral
      therapy combinations-emtricitabine/tenofovir DF + efavirenz (TVD + EFV) and
      lamivudine/zidovudine + efavirenz (COMB + EFV)-in antiretroviral-naive, HIV-1
      infected patients from the perspective of costs to society. METHODS: This cost
      effectiveness analysis was modeled using a decision tree that considered the
      therapeutic response (successful treatment episode, ie, HIV-1 RNA <400 copies/mL
      using data obtained directly from a clinical trial) and the switch to rescue
      therapy in nonresponders. The time horizon was 24 months of treatment. Cost was
      defined as direct medical costs (drugs, diagnostic and/or laboratory tests,
      treatment of adverse effects) and indirect medical costs (productivity losses).
      All data are presented as euro(2005). Sensitivity analysis was 1-factor
      threshold, adjustment of ex-factory cost, only direct costs, and applying
      discount rate in the study. The results are presented as incremental costs,
      success rates, and cost per patient with undetectable viral load or additional
      success. RESULTS: The expected 48-week cost of the regimen that includes TVD +
      EFV was euro46,464, and for the regimen that included COMB + EFV, euro56,198.
      Therefore, savings of euro9734 were achieved for each patient treated with TVD +
      EFV, as well as a gain of 13% of patients with undetectable viral load after 24
      months of treatment. Consequently, treatment with TVD + EFV combination would be
      dominant in therapy for antiretroviral-naive, HIV-1-infected patients.
      Sensitivity tests supported the stability of the base-case analysis. The cost
      effectiveness ratios were euro619.52 for the TVD + EFV regimen versus euro906.41
      for the COMB + EFV regimen. CONCLUSION: Based on the results of this analysis,
      patients who started treatment of HIV-1 infection with combination TVD + EFV had
      significantly lower health care resource utilization and overall treatment costs
      compared with the COMB + EFV combination.

PMID- 18343276
TI  - Economic evaluation of sunitinib malate in second-line treatment of metastatic
      renal cell carcinoma in Finland.
AB  - BACKGROUND: Cytokine therapy is currently used as first-line treatment of
      metastatic renal cell carcinoma (mRCC). Until recently, treatments with proven
      efficacy after the failure of first-line cytokine therapy were not available. In
      recent clinical trials, sunitinib has been associated with good response rates in
      patients with mRCC. OBJECTIVE: The aim of this study was to analyze the cost
      effectiveness of sunitinib as second-line therapy for cytokine-refractory mRCC
      compared with current routine clinical practice in Finland (ie, best supportive
      care [BSC], including palliative biochemotherapy). METHODS: A probabilistic
      decision-analytic model was developed to estimate the cost-effectiveness of
      sunitinib. Data were gathered from clinical trials, literature sources, and
      expert opinions, as well as from a local sample (n = 39) from 2 university
      hospitals in Finland. Clinical experts treating patients with mRCC in Finland
      provided the information on care practices of prescribing sunitinib. The analysis
      was conducted from the perspective of the health care payer in Finland. RESULTS:
      According to estimated incremental cost-effectiveness ratios (ICERs), 1
      progression-free month gained cost euro4802 (2005 Euros); 1 life-year gained cost
      euro30,831; and 1 quality-adjusted life-year (QALY) gained cost euro43,698,
      compared with BSC, in the treatment of mRCC. The expected mean cost in BSC was
      euro5543. When parameter uncertainty was considered, the probability of sunitinib
      being the more cost-effective choice of treatment was ~70% at the willingness-to
      pay level of euro45,000/QALY gained. CONCLUSIONS: Based on the results of this
      cost-effectiveness analysis, sunitinib is potentially cost-effective as a second
      line treatment of mRCC compared with the treatment currently practiced in Finnish
      hospitals. The ICER (euro/QALY gained) obtained in the present study was less
      than the value considered suitable for novel oncology treatments.

PMID- 18343277
TI  - Validity, reliability, and responsiveness of the work productivity and activity
      impairment questionnaire in Crohn's disease.
AB  - BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease usually
      diagnosed in early adult life and characterized by unpredictable flares and
      debilitating symptoms such as diarrhea, abdominal pain, and fever, which can
      interfere with a patient's ability to work and perform daily activities.
      OBJECTIVE: The aim of this study was to assess the validity, reliability, and
      responsiveness of the Work Productivity and Activity Impairment questionnaire in
      CD (WPAI:CD). METHODS: The WPAI:CD was tested in CD patients enrolled in a 26
      week randomized clinical trial of cer-tolizumab pegol versus placebo.
      Discriminative validity of WPAI:CD absenteeism, presenteeism(reduced on-the-job
      effectiveness), overall work productivity loss (absenteeism + presenteeism), and
      activity impairment scores was assessed relative to 5 measures of disease
      severity and health status: CD Activity Index (CDAI), Short Form-36 physical
      component summary (PCS) and mental health component summary (MCS) scores,
      Inflammatory Bowel Disease Questionnaire (IBDQ), and the 5-dimensional EuroQoL
      health-related quality-of-life visual analog scale (EQ-VAS). Responsiveness was
      assessed by comparing changes in WPAI:CD scores from baseline to week 26 for
      patients in remission (CDAI <150 points) versus no remission. Standardized
      Response Means (SRMs) were calculated to evaluate the magnitude of the changes.
      RESULTS: A total of 662 patients (mean [range] age, 37.4 [18-77] years; male, 288
      [43.5%]; white, 629 [95.0%]) were enrolled in the study. Patients with CD of the
      worst severity (CDAI > median) showed significantly higher impairment in work
      (+10.5%) and activities (+10.4%) versus patients with "best health" (no problems)
      (both, P < or = 0.001). Patients with "worst" IBDQ, PCS, MCS, and EQ-VAS scores
      also showed significantly higher impairments in work (IBDQ, VAS -24.2%; PCS, 
      24.1%; MCS, -15.9%; EQ-VAS, -16.5%) and activities (IBDQ, -23.3%; PCS, -21.8%;
      MCS, -16.5%; EQ-VAS, -17.2%) versus "best" scores (all, P < 0.05). There were
      significant differences between WPAI:CD impairment scores for patients in
      remission versus patients failing to achieve remission (P < 0.05). SRMs were
      small (ie, <0.5) in the nonre-mission group, and moderate to large (ie, >0.5) for
      patients in remission. CONCLUSIONS: The discriminative validity, reliability, and
      responsiveness of the WPAI:CD were demonstrated. The WPAI:CD may be useful for
      evaluating drug impact on CD.

PMID- 18343278
TI  - Patterns of treatment for restless legs syndrome in primary care in the United
      Kingdom.
AB  - BACKGROUND: The dopamine agonists pramipexole and ropinirole are licensed for the
      treatment of moderate to severe idiopathic restless legs syndrome (RLS) in Europe
      and the United States. In addition, various drugs that are not approved for this
      indication have been used for symptomatic treatment of RLS, including analgesics,
      quinine, and anxiolytics. OBJECTIVE: The purpose of this analysis was to describe
      patterns of treatment of newly diagnosed RLS, including treatment effectiveness
      and resource utilization, in primary care in the United Kingdom. METHODS: This
      was a cohort study that employed the UK General Practice Research Database. Two
      cohorts were assembled, one consisting of patients with an initial diagnosis of
      RLS between 1990 and 2004 and the other consisting of patients without RLS
      matched to cases in a 10:1 ratio by general practice, year of birth, sex, and
      registration with the practice on the case index date (date of the RLS
      diagnosis). The frequency of RLS-specific symptoms was estimated based on records
      of prescriptions for sleep medications and antidepressants, and reported cramps
      and leg problems other than RLS. Rates of resource use in the 2 years before and
      after the index date were estimated for both cohorts based on the numbers of
      total prescriptions, referrals to secondary care, and laboratory tests. RESULTS:
      The RLS cohort comprised 8621 patients and the matched cohort 85,087 patients.
      Age and sex distributions were comparable between groups. The annual frequency of
      prescriptions for sleep medications in the RLS cohort increased significantly
      from 19.8% and 21.6% in the 2 years before the diagnosisof RLS to 27.4% in the
      first year after the diagnosis and 25.2% in the second year (all comparisons, P <
      0.001). A similar pattern was observed for antidepressants in the RLS cohort
      (23.5%, 26.7%, 31.0%, and 29.6%, respectively; P < 0.001). Prescription rates
      were nearly constant in the matched cohort. The frequency of cramps and other leg
      problems was highest in the year before the diagnosis of RLS, declined in the
      first year after the diagnosis, and increased thereafter. Compared with the
      matched cohort, rates of prescriptions, referrals, and laboratory tests ranged
      from 49.7% to 59.0% higher in the RLS cohort in the 2 years before the diagnosis
      of RLS and from 63.4% to 91.4% higher in the 2 years after the diagnosis (all
      comparisons, P < 0.001). CONCLUSION: In patients with newly diagnosed RLS in this
      UK primary care cohort, use of medications that are not approved for the
      treatment of RLS was not associated with a reduction in clinical symptoms or
      health care resource utilization between 1990 and 2004.

PMID- 18343279
TI  - Analysis of the association between polypharmacy and socioeconomic position among
      elderly aged > or =77 years in Sweden.
AB  - BACKGROUND: Polypharmacy is an important patient safety concern and has been
      associated with increased adverse drug reactions, hospitalization, and mortality
      in the elderly. However, few studies have analyzed the association between
      socioeconomic position (SEP) and the extent of drug use in older people.
      OBJECTIVES: The aims of this study were to investigate the prevalence of
      polypharmacy and the association between polypharmacy and SEP, as measured by
      education, occupation, and income. METHODS: For this cross-sectional study, data
      from a nationally representative sample (Swedish Panel Study of Living Conditions
      of the Oldest Old [SWEOLD] 2002) aged > or =77 years were analyzed (n = 621).
      Information on drug use was based on personal interviews, and polypharmacy was
      defined as concurrent use of > or =5 drugs. Other measurements included were age,
      sex, education, occupation, income, comorbidity, marital status, and living
      situation. The association between polypharmacy and SEP was assessed by logistic
      regression. RESULTS: The mean number of drugs used in the sample was 4.4; in less
      educated patients, 4.6; more educated, 4.0. Polypharmacy was observed in 42.2% of
      the elderly. Overall, antithrombotic agents (42.5%), P-blocking agents (28.3%),
      and high-ceiling diuretics (28.0%) were the most prevalent drugs. Low education
      was associated with polypharmacy (odd ratio [OR], 1.46; 95% CI, 1.02-2.07), after
      controlling for age and sex. However, the association between low education level
      and polypharmacy was not significant after adjustment for age, sex, comorbidity,
      marital status, and living situation (OR, 1.39; 95% CI, 0.95-2.04). Moreover, we
      did not observe any association between occupation or income and polypharmacy.
      CONCLUSIONS: The results from this study suggest that >40% of people aged > or
      =77 years in Sweden are exposed to polypharmacy, defined as the use of > or =5
      drugs. There was a higher prevalence of polypharmacy among elderly with low
      education. However, after controlling for comorbidity, martial status, and living
      situation, polypharmacy was not related to low education. Further studies in
      larger populations are needed to elucidate the association between SEP and drug
      use.

PMID- 18343280
TI  - Temsirolimus downregulates p21 without altering cyclin D1 expression and induces
      autophagy and synergizes with vorinostat in mantle cell lymphoma.
AB  - OBJECTIVE: To investigate the mechanisms of antiproliferative effect induced by
      the mammalian target of rapamycin (mTOR) inhibitor temsirolimus in mantle cell
      lymphoma (MCL). MATERIALS AND METHODS: The antiproliferative effect of
      temsirolimus on three well-defined MCL cell lines was examined by the MTS assay.
      Induction of cell-cycle arrest, autophagy, and apoptosis were determined by
      fluorescence-activated cell sorting analysis. The molecular mechanisms
      underlining these effects were determined by Western blot. Synergy between
      temsirolimus and vorinostat were examined by MTS assay and the combination index
      was calculated. RESULTS: Temsirolimus has antiproliferative activity in three MCL
      cell lines in a dose- and time-dependent manner. Mechanistically, temsirolimus
      inhibited mTOR, as evidenced by inhibition of ribosomal S6 phosphorylation, and
      induced cell-cycle arrest in the G(0)/G(1) phase and a decrease in p21 expression
      without altering p27 or cyclin D1 levels. Furthermore, temsirolimus increased the
      number of acidic vesicular organelles and the amount of microtubule-associated
      protein 1 light-chain 3 processing, which are characteristic of autophagy,
      without induction of apoptosis. These changes were not associated with alteration
      in phosphorylated extracellular signal-regulated kinase (ERK), beclin-1, Bax, or
      Bak levels. In contrast, treatment of these cell lines with the histone
      deacetylase inhibitor vorinostat decreased ERK phosphorylation, activated caspase
      3, and induced apoptosis. Moreover, temsirolimus synergized with submaximal
      concentrations of vorinostat in all MCL cell lines. CONCLUSION: This is the first
      report of temsirolimus-induced autophagy in MCL, and of vorinostat inhibition of
      ERK phosphorylation in MCL. Collectively, these data suggest that the combination
      of temsirolimus and vorinostat have synergistic antiproliferative activity in MCL
      cells by distinctively targeting apoptosis and autophagy.

PMID- 18343281
TI  - Patient satisfaction after open carpal tunnel release correlates with depression.
AB  - PURPOSE: To test the null hypothesis that depression does not correlate with
      patient satisfaction after open release of electrodiagnostically confirmed carpal
      tunnel syndrome when controlling for other demographic, disease-related, and
      psychosocial factors. METHODS: Eighty-two survey respondents who had recovered
      (minimum 2 years after surgery) from a limited incision open carpal tunnel
      release completed measures of satisfaction, perceived disability, depression,
      pain catastrophizing, and pain anxiety. Univariate and multivariate analyses
      sought predictors of satisfaction and perceived disability from among
      demographic, disease related, and psychological factors. RESULTS: The average
      satisfaction score was 8 points (range, 0-10) and the average Disabilities of the
      Arm, Shoulder, and Hand score was 13 points (range, 0-76). Predictors of greater
      dissatisfaction included greater depression and the categorical
      electrophysiologic test rating. Predictors of perceived disability included
      depression, pain catastrophizing, and static numbness. Depression was the
      dominant predictor of both satisfaction and perceived disability. CONCLUSIONS:
      Dissatisfaction and perceived disability after limited open carpal tunnel release
      for electrodiagnostically confirmed idiopathic carpal tunnel syndrome is
      predicted primarily by depression and ineffective coping skills and to a lesser
      degree by clinical or electrophysiologic evidence of advanced nerve damage. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

PMID- 18343282
TI  - Brachial plexus birth palsy-associated shoulder deformity: a rat model study.
AB  - PURPOSE: Although recovery occurs in the majority of cases of brachial plexus
      birth palsy (BPBP), long-term shoulder disability is relatively common. The aim
      of this study was to establish an animal model to study BPBP-associated shoulder
      deformities. METHODS: A right-side C5, C6 root neurotomy was performed under the
      surgical microscope in 5-day-old Sprague-Dawley rats (N = 9). The contralateral
      side served as a control. The development of shoulder deformity and range of
      motion loss were followed longitudinally. Animals were killed 4 months after
      surgery. Both shoulders were harvested, decalcified, and transected in the axial
      plane for glenoid version measurement and shoulder histology. RESULTS: All
      animals developed shoulder internal rotation contracture within 4 weeks after the
      C5, C6 neurotomy. The average shoulder external rotation loss was 52 degrees +/-
      7, 59 degrees +/- 10, and 82 degrees +/- 11 in comparison with the control side
      1, 2, and 4 months after neurotomy, respectively. Glenoid version changed from 2
      degrees +/- 2 of retroversion (left side) to 8 degrees +/- 3 of anteversion. Five
      shoulders were subluxated clinically with a pseudoglenoid formation observed
      radiographically. Histologic study demonstrated marked glenoid and humeral head
      deformities. CONCLUSIONS: This neonatal rat model clearly demonstrated typical
      shoulder deformities similar to that resulting from Erb's palsy. This model can
      be useful in studying BPBP-associated shoulder deformities.

PMID- 18343283
TI  - Reconstruction of a 4-cm human median nerve gap by including an autogenous nerve
      slice in a bioabsorbable nerve conduit: case report.
AB  - Nerve gaps up to 3 cm in length can be reconstructed in the human with a
      bioabsorbable nerve conduit; however, nerve gaps greater than 3 cm have not been
      reconstructible in animal models unless a neurotrophic factor, like cultured
      Schwann cells, was added to the nerve conduit. It is the purpose of this article
      to present the result of human nerve regeneration across a 4-cm nerve gap in the
      median nerve at the wrist when a slice of autogenous normal nerve was placed into
      the middle of a bioabsorbable nerve conduit.

PMID- 18343284
TI  - Comparison of metacarpal plating methods.
AB  - PURPOSE: Most metacarpal fractures are stable and can be treated with nonsurgical
      stabilization. However, some metacarpal fractures are treated with open reduction
      and internal fixation because of an open fracture, instability, or multiple
      fractures. Newer plate designs have emerged that allow a shorter plate and screw
      construct. We sought to determine the relative strength of 3 different methods of
      metacarpal plating for unstable fractures. METHODS: We tested our hypothesis in a
      transverse metacarpal fracture model using fourth-generation, biomechanical
      testing grade composite sawbones (Sawbones; Pacific Research Laboratories,
      Vashon, WA). The metacarpals were divided into 3 groups of 15 bones. Group 1 was
      plated with a standard 6-hole, 2.3-mm plate with 6 nonlocking bicortical screws
      in standard AO fashion. Group 2 was plated with a 6-hole, double-row, 3
      dimensional (3D) plate with 3 nonlocking screws on either side of the fracture
      aiming for convergence of the screws. Group 3 was plated with a 2.4-mm plate
      using 6 nonlocking screws and standard AO technique. The metacarpals were then
      tested to failure in cantilever bending mode. RESULTS: All constructs broke
      through the bone. No plate failure or screw pullout was seen. Group 1 had a load
      to failure of 264 N +/- 14. Group 2 had a load to failure of 302 N +/- 17. Group
      3 had a load to failure of 274 N +/- 20. The load to failure was highest in group
      2 (3D plate). All differences were statistically significant. CONCLUSIONS: All 3
      methods produced a strong construct. The load to failure was highest in group 2
      (3D plate). Double-row plates with converging screws provide adequate or superior
      strength of fixation when compared with standard plate constructs.

PMID- 18343285
TI  - Biomechanical characteristics of nonbridging external fixators for distal radius
      fractures.
AB  - PURPOSE: Nonbridging external fixation is becoming popular for distal radius
      fractures, although its biomechanical characteristics have not been documented.
      This study evaluated the biomechanical characteristics of nonbridging external
      fixators for distal radius fractures. METHODS: We tested 3 currently available
      nonbridging fixators (F-Wrist fixator, Hoffman II Compact, and Pennig Dynamic
      Wrist Fixator) and determined their relative stiffness under axial compression,
      torsion, and bending moments (dorsal, volar, radial, and ulnar aspects) using a
      uniform unstable distal radius fracture model. The contact pressure and its total
      load on the fracture plane were also measured to evaluate the mechanical stimuli
      at the stable fracture site using a pressure-sensitive conductive rubber sensor.
      RESULTS: Differences were observed in the stiffness: the Pennig fixator was the
      stiffest, whereas the F-Wrist fixator was the least rigid. The total load
      transmitted from the wrist joint to the fracture plane depended on the fixator
      stiffness in axial compression. CONCLUSIONS: By determining the biomechanical
      characteristics of nonbridging external fixators, these data may help the
      clinician when deciding on a particular device for nonbridging external fixation.

PMID- 18343286
TI  - Percutaneous fixation of the scaphoid through a dorsal approach: an anatomic
      study.
AB  - PURPOSE: Percutaneous surgical treatment of nondisplaced scaphoid fractures is
      becoming more common. Although the surgical anatomy at risk has been well
      described for the volar approach to the scaphoid, we have not found articles
      elucidating the dangers with a percutaneous dorsal approach. Additionally, direct
      placement of the screw is not possible with a percutaneous approach, and there is
      a risk of not seating the screw below the subchondral bone. The purpose of this
      study was to delineate the anatomy at risk using a dorsal percutaneous approach
      to the scaphoid and to determine the accuracy of using fluoroscopy to seat the
      screw flush with the subchondral surface. METHODS: Cannulated, headless screws
      were placed into the scaphoids of 12 fresh-frozen cadavers in standard
      percutaneous fashion through a dorsal approach. Fluoroscopy was used to seat the
      screw just below the subchondral surface. The wrists were then dissected and the
      distance from the guide wire to various anatomic structures was measured. The
      distance that the screw was protruding above or buried below the subchondral bone
      was also measured. RESULTS: The distances from the guide wire to the posterior
      interosseous nerve, to extensor digitorum communis to the index, and to extensor
      indicis proprius were 2.2 mm, 2.2 mm, and 3.1 mm, respectively. These structures
      were most at risk. The screw was prominent (above the subchondral bone) in 2 of
      12 specimens and flush with or buried in the remaining 10 specimens. CONCLUSIONS:
      The results of this study show that there are anatomic structures at risk of
      injury with dorsal percutaneous placement of a headless screw into the scaphoid.
      Despite using live and static fluoroscopy views, we incorrectly placed the screw
      above the subchondral bone in 2 of the specimens. We support use of a limited
      incision when internally fixing a scaphoid from the dorsal approach.

PMID- 18343287
TI  - The incidence of dorsal radiocarpal ligament tears in patients having diagnostic
      wrist arthroscopy for wrist pain.
AB  - PURPOSE: The goal of this study was to examine the incidence of dorsal
      radiocarpal ligament (DRCL) tears in patients having diagnostic arthroscopy for
      chronic wrist pain. METHODS: A chart review was performed of 64 patients who had
      diagnostic wrist arthroscopy for chronic wrist pain that was refractory to
      conservative measures. For each case, interosseous ligament instability/tears
      were graded according to the Geissler classification. Tears of the triangular
      fibrocartilage complex and the presence or absence of a DRCL tear were noted.
      RESULTS: There were 35 of 64 wrists (in 64 patients) with DRCL tears. The average
      duration of wrist pain prior to treatment was 20 months. Only 10 patients could
      recall a specific injury. Five patients had an isolated DRCL tear. A scapholunate
      interosseous ligament injury was identified in 13 patients, of whom 7 had a
      concomitant DRCL tear. A lunotriquetral interosseous ligament injury was present
      in 7 patients, of whom 2 had a concomitant DRCL tear. Two patients had a
      capitohamate ligament tear: 1 of these patients had a DRCL tear. There were 7
      patients with a solitary triangular fibrocartilage complex tear: 6 of 7 were in
      association with a DRCL tear. One patient had a chronic ulnar styloid nonunion
      and a DRCL tear. Two or more lesions were present in 23 patients; DRCL tears were
      present in 12. CONCLUSIONS: DRCL tears are commonly seen with injuries to the
      primary wrist stabilizers. Recognition of this condition and further research
      into treatment methods are needed. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic
      IV.

PMID- 18343288
TI  - Plain radiographs are inadequate to identify overlengthening with a radial head
      prosthesis.
AB  - PURPOSE: A correctly sized radial head implant helps restore more normal elbow
      motion and load distribution and allows the collateral ligaments to heal in an
      anatomic position. No single method of measurement has been agreed on. We
      hypothesized that plain radiographs could be used to evaluate the appropriate
      length of a radial head prosthesis when we simulated different patterns of
      ligament disruption. METHODS: Osteotomies of the medial and lateral condyles were
      created in 6 cadaver specimens to simulate 4 conditions: ulnar collateral
      ligament (UCL) and lateral ulnar collateral ligament (LUCL) intact, UCL intact,
      LUCL intact, and UCL and LUCL disrupted. Radial heads were resected and replaced
      with correctly or incorrectly sized monopolar radial head implants. Radiographs
      were taken after simulated ligament injury with a radial head prosthesis that was
      either 2 mm too short, the appropriate length, or too long by either 2 or 4 mm.
      Measurements were recorded between radiographic markers to determine ulnohumeral
      joint displacement. A 4 x 4 x 2 repeated-measures analysis of variance was
      performed, as well as post hoc analyses using Tukey's honest significant
      difference test, to determine statistically significant changes in our
      radiographic measurements. RESULTS: Results showed that disruption of at least 1
      ligament alters the ulnohumeral joint separation on the lateral but not on the
      anteroposterior radiograph. Overlengthening the radial head did not result in a
      statistically significant change in ulnohumeral space. CONCLUSIONS: Replicating
      radial length is an important but sometimes difficult step during radial head
      replacement. Standard radiographic assessment of the ulnohumeral joint will not
      demonstrate marked changes in the ulnohumeral space when the implant is
      underlengthened by 2 mm or overlengthened by as much as 4 mm, as long as the
      joint remains located. Disruption of at least 1 collateral ligament alters the
      ulnohumeral joint separation on the lateral but not on the anteroposterior
      radiograph.

PMID- 18343289
TI  - The spiral flap for fingertip resurfacing: short-term and long-term results.
AB  - PURPOSE: We describe a homodigital neurovascular island flap for reconstructing
      large pulp defects of the fingertips and review the short-term and long-term
      appearance and function of the reconstructed fingertips. METHODS: The spiral flap
      is a homodigital neurovascular island flap with a unique spiral advancement and
      transposition design that allows pulp reconstruction using sensate glabrous skin
      while restricting donor morbidity to the injured digit. Thirty-two fingertips
      were resurfaced using this flap. All had large pulp defects averaging 1.2 cm wide
      x 2.0 cm long (1.0-2.0 cm x 1.5-2.5 cm). Short-term results (<18 months) for all
      patients at a minimum of 6 months and long-term results (>5 years) for 10
      patients with a mean follow-up of 13 years were reviewed. Objective outcome
      measures included static 2-point discrimination, degree of nail deformity
      (beaking), total active motion, and hypersensitivity or cold intolerance.
      Subjective outcome measures included patient satisfaction with function and
      aesthetics, using a visual analog scale. RESULTS: All flaps achieved primary
      healing with no complications. There was initially mild extension deficit in the
      proximal interphalangeal and distal interphalangeal joints, which improved to
      full range of motion in the long term. Sensory recovery was excellent, with an
      average 2-point discrimination of 5 mm initially, improving to 4 mm in the long
      term. Nail beaking was minimal initially but increased significantly in the long
      term. These results may be explained by soft tissue remodeling. All patients on
      long-term follow-up were highly satisfied with both aesthetic and functional
      outcome. There was no hypersensitivity or cold intolerance at either the short
      term or long-term follow-up assessments. CONCLUSIONS: The spiral advancement
      transposition flap is suitable for resurfacing large pulp defects with excellent
      short-term and long-term functional and aesthetic results and high patient
      satisfaction. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18343290
TI  - Treatment of posttraumatic painful neuromas at the digit tip using neurovascular
      island flaps.
AB  - PURPOSE: We report the treatment of 9 patients with 9 painful neuromas at the
      tips of the digits using reverse pedicled island flaps containing subcutaneous
      nerves that were connected to the digital nerve stumps after removal of the
      neuromas. METHODS: There were 9 patients (7 men and 2 women) with painful
      cutaneous neuromas at the tips of the digits. The ages of the patients at time of
      surgery were 21 to 66 years (mean, 46 y). All neuromas were formed in the palmar
      digital nerves in the hand. Preoperative and postoperative status of the patients
      with neuromas were assessed and graded using a system modified from previously
      described grading systems for patients with neuromas. Recovery of sensation in
      the transplanted skin islands was assessed using the Semmes-Weinstein
      monofilament test. RESULTS: In the preoperative assessment of patients using the
      grading system for neuromas, 3 patients were assessed as grade 4 (severe), 5
      patients as grade 3 (moderate), and the remaining patient as grade 2 (mild).
      After surgery, Tinel sign disappeared completely in 6 of 9 patients. According to
      the grading system for neuromas, 6 patients were assessed as grade 1 (normal),
      and the other 3 patients were assessed as grade 2 (mild) postoperatively. Using
      the Semmes-Weinstein monofilament test for assessing recovery of sensation of the
      skin islands, 3 patients recognized the 2.83 monofilament (normal), 2 patients
      recognized the 3.22 monofilament (loss of tactile sense), and the remaining 4
      patients recognized the 3.66 monofilament applied (loss of tactile sense).
      CONCLUSIONS: This skin island approach provided us with good pain control and
      recovery of hand function after painful neuromas. TYPE OF STUDY/LEVEL OF
      EVIDENCE: Therapeutic IV.

PMID- 18343291
TI  - The effects of freezing on the tensile properties of repaired porcine flexor
      tendon.
AB  - PURPOSE: When conducting complex testing of tendon repairs, it is essential that
      the samples are adequately preserved to prevent degradation. Freezing of samples
      is the most convenient method of preservation; however, there is no evidence in
      the literature to prove that freezing tendon before or after repair is
      acceptable. We aimed to prove that freezing tendons does not significantly alter
      the results of linear load-to-failure testing of tendon repairs. METHODS: After a
      power study, 150 tendons were harvested from porcine forelimbs and randomized
      into 5 groups of 30 tendons. After division, tendons were repaired using a
      Pennington modified core technique with a Silfverskiold peripheral cross-stitch.
      Tendons in group 1 were divided, repaired, and tested within 3 hours postmortem.
      Tendons in group 2 were refrigerated at 4 degrees C for 24 hours prior to repair
      and testing. Tendons in group 3 were frozen at -25 degrees C for 3 months prior
      to repair and testing. Tendons in group 4 were frozen at -25 degrees C for 6
      months prior to repair and testing. Tendons in group 5 were frozen at -25 degrees
      C for 6 months, repaired, refrozen for 1 month, and then tested. All repairs were
      linear load tested to ascertain the ultimate strength and force to produce 3-mm
      gap in the repair. RESULTS: Analysis of variance analysis of the results did not
      demonstrate any significant differences between groups. CONCLUSIONS: Freezing
      tendons both before and after suture repair is an acceptable method of
      preservation when investigating the force to produce 3-mm gap and ultimate
      strength of tendon repairs.

PMID- 18343292
TI  - Molecular phenotypic descriptors of Dupuytren's disease defined using informatics
      analysis of the transcriptome.
AB  - PURPOSE: Dupuytren's disease (DD) is a fibroproliferative disorder of unknown
      etiopathogenesis, which may cause progressive, permanent contracture of digits.
      Previous studies provide compelling evidence that genetic alterations play an
      important role. Macroscopically affected areas demonstrate phenotypic differences
      between the two structurally distinct fibrotic elements in DD (ie, the nodule and
      the cord). In this study, we set out to (1) compare gene expression profiles
      between DD and transverse carpal fascia of control subjects (external control);
      (2) profile DD cords and nodules from the palm against the unaffected transverse
      palmar fascia (internal control); and (3) identify biologically important
      candidate genes from the transcriptome profiles. METHODS: RNA samples from DD
      nodules (n = 4), cords (n = 4), and internal control (n = 4) as well as external
      control (n = 4) from unaffected individuals were subjected to differential gene
      expression profile analysis. Changes of more than 2-fold in DD groups and
      controls were recorded. Quantitative reverse transcriptase-polymerase chain
      reactions were performed to validate 16 implicated genes, which included
      developmental control genes, matrix metalloproteinases, and apoptotic genes.
      RESULTS: Several genes associated with DD formation were common across all 6
      pairwise analyses. Genes markedly upregulated shared common expression levels
      across all pairwise analysis studies. Pairs involving the DD nodule arrays were
      notably distinguishable from all other permutations. The majority of genes
      dysregulated in the DD cords demonstrated an increase in fold change when
      compared with the DD nodule tissues. Key collagens, collagenases,
      metalloproteinases, and inhibitors were identified. Genes involved in
      cytoskeleton development and lipid metabolism were markedly dysregulated.
      Confirmations of these alterations were obtained in quantitative reverse
      transcriptase-polymerase chain reaction. CONCLUSIONS: These data demonstrate a
      gradation in expression of certain genes in DD tissue phenotypes compared with
      control fascia. Transcriptome profiling is predictive not only of disease but
      also of disease phenotype. These results indicate a number of important candidate
      genes associated with DD formation, which may provide clues for molecular
      mechanisms involved in DD pathogenesis.

PMID- 18343293
TI  - A classification system of radial polydactyly: inclusion of triphalangeal thumb
      and triplication.
AB  - PURPOSE: Radial polydactyly is a congenital anomaly with a wide range of
      manifestations. Current classifications do not have the capacity to classify all
      different types of radial polydactyly when combined with triphalangeal
      components. The objective of this study was to test an adjusted classification
      and nomenclature that allows classification of triphalangeal components and
      triplication in radial polydactyly. METHODS: Patients from 1993 to 2006 with
      radial polydactyly (N = 104), a total of 121 affected hands, were identified from
      the hospital database. All x-rays were carefully examined and classified
      according to the existing classifications for radial polydactyly and a modified
      classification. In the modified nomenclature, Wassel's level of duplication is
      preserved. Type VII and VIII are assigned for partial or complete duplication of
      the carpal bones according to Buck-Gramcko. Triplication and triphalangeal
      components can be assigned to each type of radial polydactyly by suffixes.
      Symphalangism, deviation, and hypoplasia can also be classified. Triplication on
      different levels of the thumb is classified by determining and including the
      different types of the original Wassel classification. RESULTS: Eighteen thumbs
      could not be classified according to existing classifications for radial
      polydactyly with triphalangeal components or triplication. Using the proposed
      classification, all patients could be classified. CONCLUSIONS: We propose a
      modified classification that is a practical and utilitarian scheme for
      nomenclature of radial polydactyly and that may assist comparison of treatment
      outcomes and individual cases. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

PMID- 18343294
TI  - Hand span influences optimal grip span in boys and girls aged 6 to 12 years.
AB  - PURPOSE: The first aim was to determine whether there is an optimal grip span for
      determining the maximum hand grip strength in boys and girls aged 6 to 12 years
      and whether the optimal grip span was related to hand span. If so, the second aim
      was to derive a mathematical equation relating hand span and optimal grip span.
      METHODS: A total of 123 boys (9 y +/- 2) and 70 girls (8 y +/- 2) were evaluated.
      Each hand was randomly tested on 10 occasions using 5 different grip spans,
      allowing a 1-minute rest between attempts. The hand span was measured from the
      tip of the thumb to the tip of the little finger with the hand opened widely.
      RESULTS: An optimal grip span to determine maximum hand grip strength was
      identified for both genders. Hand span and optimal grip span showed a significant
      linear association in the studied children. The equation relating grip span as a
      function of hand span in boys is formulated as y = x/4 + 0.44 and in girls as y =
      0.3x - 0.52, where x is the hand span (maximal width between first and fifth
      fingers) and y is the optimal grip span. CONCLUSIONS: The results suggest that
      there is an optimal grip span to which the dynamometer should be adjusted when
      measuring hand grip strength in children. The optimal grip span was influenced by
      hand span in both genders.

PMID- 18343295
TI  - Multiplier method for limb-length prediction in the upper extremity.
AB  - PURPOSE: Limb-length discrepancy occurs in both the upper and lower extremities.
      Methods of predicting discrepancies at skeletal maturity have generally focused
      on the lower limbs. Paley et al devised the multiplier method to predict lower
      limb-length discrepancy at skeletal maturity. The purpose of this study was to
      generate a similar methodology applicable for the upper limb. METHODS: Using
      radiographic, clinical, and anthropologic databases, we divided humeral, radial,
      and ulnar lengths at skeletal maturity by the humeral, radial, and ulnar lengths
      at each age and for each percentile given. The multipliers for the radius, the
      ulna, and the humerus were compared with each other. The multipliers also were
      compared based on percentile, ethnic and racial group, nationality, and
      anthropologic data. RESULTS: The multipliers for the humerus, radius, and ulna
      were equivalent in all percentile groups, varying only by age and gender after 1
      year of age. The multipliers of different national and racial groups also were
      the same. The upper-extremity multipliers calculated from anthropologic data were
      very similar. CONCLUSIONS: The multiplier method is a quick and easy method of
      predicting upper-limb growth. It is simpler to use than previous methods and is
      independent of percentile, generation, ethnicity, nationality, and race. The
      upper-extremity multiplier can be used to determine timing of epiphysiodesis and
      predict bone length at skeletal maturity, growth remaining, and congenital and
      developmental limb-length discrepancy. TYPE OF STUDY/LEVEL OF EVIDENCE:
      Prognostic II.

PMID- 18343296
TI  - Extensor indicis proprius transfer for the abducted small finger.
AB  - PURPOSE: Persistent abduction of the small finger has usually been treated by
      transfer of the extensor digiti minimi muscle. However, anatomic variations of
      the extensor system may limit the potential for a successful extensor digiti
      minimi transfer. Therefore, we evaluated the outcomes of an alternative
      reconstruction method for the abducted small finger using an extensor indicis
      proprius (EIP) transfer. METHODS: We performed 8 EIP transfers in 8 patients with
      persistent, flexible abduction posturing of the small finger. The primary
      etiology of the deformity was incomplete motor reinnervation after surgeries for
      ulnar neuropathy in 6 patients, rupture of the third palmar interosseous
      musculotendinous unit in 1 patient, and intrinsic muscle fibrosis in 1 patient.
      The EIP was elongated by splitting the tendinous portion and was transferred to
      the distal and radial part of the extensor hood. Surgical outcomes were assessed
      by comparing preoperative and postoperative active adduction and abduction motion
      of the 2 ulnar digits. RESULTS: At the mean follow-up of 23 months, the average
      adduction angle improved from 19 degrees to 1 degrees postoperatively. In terms
      of active finger motion, 6 patients showed excellent results, 1 good, and 1 fair,
      without loss of flexion and extension. No patient had an extension lag or
      complained of functional deficits of the donor index finger. There was not
      adverse change to digital function or range of motion for the middle and ring
      fingers that are crossed by the EIP. CONCLUSIONS: Extensor indicis proprius
      transfer can be a reliable option for correction of abduction deformity of the
      small finger, maintaining active abduction and full flexion and extension. TYPE
      OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18343297
TI  - Sea urchin spine arthritis of the hand.
AB  - PURPOSE: Although rare, hand injury caused by puncture with the sea urchin spine
      can result in serious complications. To emphasize its clinical significance, this
      article describes a group of patients who sustained chronic granulomatous
      arthritis induced by puncture with sea urchin spine (designated sea urchin spine
      arthritis). METHODS: Five patients who developed sea urchin spine arthritis of
      the hand after puncture with sea urchin spine were treated at our hospitals. All
      lesions involved the proximal interphalangeal (PIP) joint (4 index fingers and 1
      middle finger). Patients experienced pain, swelling, and discomfort around the
      site of puncture immediately after the injury. These initial symptoms subsided
      within a few days, and secondary symptoms including fusiform swelling, limited
      motion, and mild pain of the PIP joint appeared from 1 to 2 months later.
      Laboratory tests of inflammation and blood cell counts were negative. Plain
      radiographs showed soft tissue swelling and osteolysis but no visible spine.
      Thorough synovectomy of the PIP joint was performed, and the granulation tissue
      around the joint was also removed. RESULTS: No microorganism was identified from
      tissue culture or polymerase chain reaction in any of the 5 patients. At a mean
      follow-up of 21 months, 2 patients exhibited essentially normal active motion of
      the affected PIP joint, whereas the remaining 3 patients had diminished range of
      motion. CONCLUSIONS: Diagnosis of sea urchin spine arthritis can be made by
      history of sea urchin spine injury, a symptom-free period before the development
      of synovitis, and the absence of laboratory test abnormalities. Neither
      antibiotics nor nonsteroidal anti-inflammatory agents are effective. Undertaken
      early enough, thorough synovectomy might avoid complications and obtain favorable
      results. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 18343298
TI  - An aberrant branch of the radial digital nerve in the index finger: case report.
AB  - This report describes an incidental finding of an aberrant branch of the radial
      digital nerve in the index finger of a 39-year-old woman who cut herself with a
      knife.

PMID- 18343299
TI  - Merkel cell tumor of the hand: report of two cases.
AB  - Merkel cell carcinoma is a rare cutaneous neuroendocrine neoplasm. Often located
      on the head and neck, reports of Merkel cell carcinoma in the hand are extremely
      limited. In this article, we review 2 cases of Merkel cell carcinoma of a digit
      treated with ray resection and sentinel lymph node dissection with greater than 5
      years of follow-up.

PMID- 18343300
TI  - A guide to planning and executing a surgical randomized controlled trial.
AB  - Evidence-based medicine requires that treatments given to patients demonstrate
      effectiveness. The randomized controlled trial (RCT) has become the preeminent
      study design to assess the efficacy of treatments. Randomized controlled trials
      are frequently used to evaluate pharmaceutical treatments but are less often used
      in surgery. The lack of surgical RCTs is partly due to ethical and methodological
      concerns associated with surgical interventions. We provide a guide to planning
      and conducting a surgical RCT.

PMID- 18343301
TI  - The role of prophylactic antibiotics in elective hand surgery.
AB  - The current literature has poorly defined the role of antibiotic agents in
      elective hand surgery. The reason for this may be due to a small number of well
      designed studies specifically addressing the efficacy of antibiotics in hand
      surgery. Our purpose is to critically review the current literature in an attempt
      to more precisely define the role of prophylactic antibiotics in elective hand
      surgery.

PMID- 18343302
TI  - Distal radius fracture management in elderly patients: a literature review.
AB  - Distal radius fracture management in elderly patients remains without consensus
      regarding the appropriate treatment or anticipated outcome. Forty-one studies
      that included at least 10 patients with a minimum mean age of 65 years and that
      were indexed in Medline or Embase were reviewed. Treatment methods included pins
      and plaster, external fixation, K-wires, bone cement, and open reduction and
      internal fixation with plates. The methodological quality of each study was
      evaluated through use of a grading scale. Despite study heterogeneity, higher
      rates of infection were noted with external fixation and K-wire stabilization.
      Stratifying patients into low-demand and high-demand groups may improve the
      management of distal radius fractures in elderly patients. In sedentary patients
      with low demands, functional outcomes are good despite the presence of deformity.
      Patients with higher demands may benefit from fracture stabilization with locking
      volar plates. Volar plating with fixed-angle screws may be particularly suitable
      for elderly patients who may take longer to heal a fracture, be more susceptible
      to pin-track infection, and demonstrate earlier tendon irritation leading to
      rupture.

PMID- 18343303
TI  - Medial collateral ligament injury in the overhand-throwing athlete.
AB  - Medial collateral ligament injuries are rare and occur almost exclusively in
      overhand-throwing athletes. The late cocking phase of the overhand throw places a
      marked valgus moment across the medial elbow. This repetitive force reaches the
      tensile limits of the medial collateral ligament, subjecting it to microtraumatic
      injury and attenuation. The anterior bundle of the medial collateral ligament has
      been identified as the primary restraint to valgus load and is the focus of
      reconstruction. Diagnosis of medial collateral ligament injuries should be
      suspected in any overhand-throwing athlete with a history of medial-sided elbow
      pain, decreased control, and reduced throwing velocity. Injury to the medial
      collateral ligament can be confirmed by physical examination (moving valgus
      stress test) and appropriate imaging studies (computed tomography arthrogram and
      magnetic resonance imaging). Reconstructive techniques of the medial collateral
      ligament have evolved over time and currently provide superior outcomes, with 80%
      to 90% of athletes returning to the same level of competitive play. As our
      understanding of the pathoanatomy of medial elbow injuries progresses and newer
      hybrid techniques evolve, our ability to care for the overhand-throwing athlete
      can be expected to improve.

PMID- 18343304
TI  - Traumatic thumb carpometacarpal joint dislocations.
AB  - Isolated traumatic dislocation of the thumb carpometacarpal joint, also called
      the trapeziometacarpal joint, is a rare injury. Controversy still exists
      concerning which ligaments are the true key stabilizers for the joint and
      therefore need to be damaged to result in dislocation, and optimal treatment
      strategies for thumb carpometacarpal joint dislocations are the subject of
      continuing debate. We give a review of the literature concerning traumatic
      dislocations of the carpometacarpal joint of the thumb and propose a treatment
      algorithm.

PMID- 18343305
TI  - Radial portal tendon harvest and interposition in arthroscopic treatment of thumb
      basilar joint osteoarthritis.
AB  - This study describes an arthroscopic technique that uses the same radial
      arthroscopic access portal to harvest and to interpose tendon material into the
      trapeziometacarpal joint in the treatment of Eaton-Littler stage 2 and 3
      osteoarthritis of the trapeziometacarpal joint. Clinical application of this
      technique has resolved pain and preserved motion at the trapeziometacarpal joint
      in this study experience.

PMID- 18343306
TI  - The carpal boss: review of diagnosis and treatment.
AB  - It is not uncommon to find a protruding mass at the dorsum of the wrist. The
      carpal boss is a commonly overlooked condition of unclear etiology. Minor trauma
      and persisting os styloideum are among the suspected causes of the condition.
      Long-standing carpal boss can lead to osteoarthritic damage in some patients.
      Many diagnostic tools, such as a "carpal boss view" radiographic study or a
      technetium bone scan, are available to help differentiate carpal boss from other,
      more common, masses of the dorsal aspect of wrist. For years, excision of the
      mass has been a commonly described treatment, because conservative treatment does
      not always give relief of symptoms. However, the benefits of wide excision must
      be balanced by the risks of instability at the involved joints, leading to
      persistent, and potentially worsened, symptoms.

PMID- 18343307
TI  - Stabilization of finger ulnar deviation in rheumatoid arthritis: extensor indicis
      proprius tenodesis.
AB  - Ulnar deviation of fingers in rheumatoid arthritis is a common deformity that can
      markedly compromise hand function. These deformities also result in an aesthetic
      impairment that is often troubling to patients. A variety of surgical procedures
      have been recommended to correct the ulnar deviation, either at the wrist level
      or at the metacarpophalangeal (MCP) joints. We present a surgical technique that
      uses the extensor indicis proprius as a tenodesis across the dorsum of the MCP
      joints of the fingers. The technique can also be used in conjunction with other
      surgical procedures, including prosthetic replacement arthroplasties of the MCP
      joints. The procedure has been used in 6 patients. Ulnar deviation averaged 62
      degrees preoperatively and 15 degrees postoperatively. All patients have been
      satisfied with the results.

PMID- 18343308
TI  - Integrating evolving brain-gene ontology and connectionist-based system for
      modeling and knowledge discovery.

PMID- 18343309
TI  - Low rank updated LS-SVM classifiers for fast variable selection.
AB  - Least squares support vector machine (LS-SVM) classifiers are a class of kernel
      methods whose solution follows from a set of linear equations. In this work we
      present low rank modifications to the LS-SVM classifiers that are useful for fast
      and efficient variable selection. The inclusion or removal of a candidate
      variable can be represented as a low rank modification to the kernel matrix
      (linear kernel) of the LS-SVM classifier. In this way, the LS-SVM solution can be
      updated rather than being recomputed, which improves the efficiency of the
      overall variable selection process. Relevant variables are selected according to
      a closed form of the leave-one-out (LOO) error estimator, which is obtained as a
      by-product of the low rank modifications. The proposed approach is applied to
      several benchmark data sets as well as two microarray data sets. When compared to
      other related algorithms used for variable selection, simulations applying our
      approach clearly show a lower computational complexity together with good
      stability on the generalization error.

PMID- 18343310
TI  - Concomitant boost radiotherapy compared with conventional radiotherapy in
      squamous cell carcinoma of the head and neck--a phase III trial from a single
      institution in India.
AB  - AIMS: To test the efficacy of an accelerated fractionation schedule (concomitant
      boost) against standard conventional fractionation in squamous cell carcinomas of
      the head and neck region in our patient population. MATERIALS AND METHODS:
      Patients were randomised to receive either conventional radiotherapy with 2
      Gy/fraction/day, to a dose of 66 Gy in 33 fractions over 6.5 weeks or accelerated
      radiotherapy in the form of concomitant boost to a dose of 67.5 Gy/40 fractions
      over 5 weeks (phase 1: 45 Gy/25 fractions/5 weeks and phase 2: 22.5 Gy/15
      fractions/3 weeks as a second daily fraction after a 6h gap). The primary and
      secondary end points were disease-free survival and locoregional control
      respectively. RESULTS: The compliance was 97.2% and 96.5% in the concomitant
      boost and conventional arms, respectively. Patients treated with concomitant
      boost had a better 2-year disease-free survival (71.7% vs 52.17%, P=0.0007) and
      locoregional control rates (73.6% vs 54.5%, P=0.0006) than with conventional
      fractionation. On exploratory subgroup analysis, the oropharynx (P<0.001), T4
      lesions (P=0.017), N+ disease (P<0.001) and stage IV disease (P<0.001) were
      statistically significant prognostic variables in favour of the concomitant boost
      arm. Grade 3 mucositis was seen in 35% of patients in the concomitant boost arm,
      whereas in the conventional arm only 19% of patients had grade 3 mucositis
      (P=0.01). The median radiotherapy duration in the concomitant boost arm was 36
      days (range 36-53 days), whereas in the conventional arm it was 46 days (range 46
      64 days). The mean gap in radiation treatment in the concomitant boost arm was
      1.68 days (range 0-14 days), whereas the mean gap in the conventional arm was
      1.58 days (range 0-14 days). CONCLUSIONS: Concomitant boost is a therapeutically
      superior and logistically feasible accelerated radiotherapy regimen in advanced
      head and neck cancers, especially in the setting of a developing country.

PMID- 18343311
TI  - Thyroid cancer guidelines--what's new?

PMID- 18343312
TI  - How to keep that stemmy-ness: stem cells in the spotlight.

PMID- 18343314
TI  - Malignant fibrous histiocytoma of the mandible in the context of a traumatic
      Marjolin's ulcer.
AB  - We present a rare manifestation of a chronic mandibular wound with a traumatic
      diathesis. A 38-year-old male patient sought medical consultation because of
      painless swelling in the mandibular symphysis and mild paresthesia of the lower
      lip. He mentioned a history of physical trauma to the mandibular symphysis 12
      months ago. The radiographic evaluation and CT scan showed gross destruction of
      bone leading to a well-defined radiolucent lesion without any sclerosing margins.
      The histological examination revealed numerous spindle-shaped fibroblasts
      arranged in a fascicular pattern and scattered multinucleated and mononuclear
      cells with bizarre nuclei throughout the lesion. Moderate nuclear pleomorphism
      was evident with few mitotic cells. The lesion was diagnosed as a malignant
      fibrous histiocytoma of storiform-pleomorphic type based on the previous
      descriptions. After surgical removal of the lesion and the adjacent tissues and
      reconstruction, the patient was referred to a radiotherapist for continuation of
      treatment. Despite this therapy, the lesion recurred after a year, and prior to
      the second operation, the patient died as a result of brain involvement.

PMID- 18343315
TI  - Essence of Care and the pressure ulcer benchmark--an evaluation.

PMID- 18343316
TI  - Minimally invasive technique for the surgical treatment of chronic osteomyelitis.

PMID- 18343317
TI  - Orofacial pain and dysfunction. Preface.

PMID- 18343320
TI  - The classification of orofacial pains.
AB  - This article highlights the process of making the proper orofacial pain
      diagnosis. A classification is presented based on the clinical characteristics of
      the pain complaint and the structure by which it emanates. It is meant to serve
      as a road map for the clinician, which will help him or her establish the correct
      diagnosis, thereby allowing the selection of the proper treatment.

PMID- 18343321
TI  - Classification, causation and treatment of masticatory myogenous pain and
      dysfunction.
AB  - This article focuses on chronic myogenous pains affecting the masticatory
      muscles, including focal myalgia, regional myalgia, myofascial pain, and
      fibromyalgia. The probable mechanisms are discussed and treatment options,
      including self-directed treatment, physical medicine modalities, and several
      types of pharmacologic agents, are presented.

PMID- 18343322
TI  - Internal derangements of the temporomandibular joint.
AB  - This article discusses several types of internal derangements of the
      temporomandibular joint. It includes definitions, clinical characteristics, and
      management options. Nonsurgical and surgical treatment strategies are discussed
      taking into consideration the latest evidence-based literature.

PMID- 18343323
TI  - Osteoarthritis, osteoarthrosis, and idiopathic condylar resorption.
AB  - The term "osteoarthritis" has classically been defined as a low-inflammatory
      arthritic condition. The term "osteoarthrosis," a synonym for osteoarthritis in
      the medical orthopedic literature, has recently come to be identified in the
      dental/temporomandibular joint (TMJ) disorders literature with any
      noninflammatory arthritic condition that results in similar degenerative changes
      as in osteoarthritis. The term "idiopathic condylar resorption," also known as
      "progressive condylar resorption," is described as a dysfunctional remodeling of
      the TMJ manifested by morphologic change, decreased ramal height, progressive
      mandibular retrusion in the adult, or decreased mandibular growth in the
      juvenile. This article discusses the diagnosis and management of osteoarthritic
      TMJ disorders and idiopathic condylar resorption.

PMID- 18343324
TI  - Psychological considerations for chronic orofacial pain.
AB  - This article presents an overview of psychologic and behavioral issues related to
      chronic orofacial pains. Clinicians are first introduced to the role that
      biobehavioral issues play in the onset and maintenance of orofacial pains.
      Specific foundational principles for the development of successful biobehavioral
      interventions are then presented and examples of successful biobehavioral
      treatment programs for orofacial pains are described. Positive outcomes in
      chronic orofacial pain management often require a multidimensional approach to
      treatment because of the complexity of dysfunctions. The principles and
      procedures outlined in this article can guide the development of effective
      biobehavioral management approaches for orofacial pain conditions.

PMID- 18343325
TI  - Pharmacologic management of temporomandibular disorders.
AB  - Although there are theoretically numerous pharmacologic targets for relieving
      temporomandibular disorder (TMD)-associated pains, evidence-based literature
      clearly establishing the efficacy and safety of drugs in the TMD population is
      limited at best. This article reviews the pharmacology, toxicology, and research
      supporting the use of a host of pharmacologic agents that have been used in
      patients who have TMD, including nonsteroidal anti-inflammatory drugs,
      corticosteroids, benzodiazepines, nonbenzodiazepine sedative hypnotics, opioids,
      skeletal muscle relaxants, capsaicin, transdermal lidocaine, antidepressants, and
      anticonvulsants. Recommendations regarding the proper use of each drug class are
      also made.

PMID- 18343326
TI  - Technological devices in the diagnosis of temporomandibular disorders.
AB  - Claims have been made that certain diagnostic devices should be routinely used to
      differentiate between jaw dysfunction and normal variation and between various
      pathologic conditions of the temporomandibular joint. The claims that jaw
      tracking devices have diagnostic value for detecting TMD are not well supported
      by the scientific evidence. The clinical usefulness of electromyography devices
      is limited because of technical, methodologic, and data interpretation problems,
      as well as significant overlap between asymptomatic and symptomatic groups.
      Claims for the use of sonography and vibratography machines to discriminate
      between various intracapsular TMJ conditions have not been substantiated by well
      designed research. Until acceptable levels of technical and diagnostic validity
      have been clearly established, these diagnostic devices cannot be relied on as
      aids in differential diagnosis or in clinical decision making in the TMD field.

PMID- 18343328
TI  - Neuropathic orofacial pain.
AB  - Neuropathic orofacial pain is a general term employed to describe a number of
      clinical syndromes, which may be spontaneous or triggered by local trauma or
      systemic disorders. Symptomatically these painful syndromes may be episodic or
      continuous and are often difficult to distinguish from dental pathology. In the
      present article, we review the diagnosis, pathophysiology and therapeutic
      approaches to trigeminal and glossopharyngeal neuralgias, orofacial pain
      associated with herpetic infection, persistent idiopathic facial pain (previously
      termed atypical facial pain), post-traumatic orofacial neuropathy and neuritis.

PMID- 18343327
TI  - Neurovascular pains: implications of migraine for the oral and maxillofacial
      surgeon.
AB  - Epidemiologic studies have shown that migraine headaches are a common finding in
      the general population, often associated with a high degree of disability.
      Additionally, migraine has a reported comorbidity with other medical conditions,
      most notably with chronic pains, such as temporomandibular disorders. The
      pathophysiologic mechanisms involved with migraine are suggestive of an increased
      and prolonged hyperexcitability to stimuli, especially within the trigeminal
      distribution. Because migraine is mediated by branches of the trigeminal nerve it
      has the potential to mimic other types of pains, such as toothache or sinusitis.
      It is therefore recommended that oral and maxillofacial surgeons be familiar with
      the diagnostic criteria for migraine headaches to identify and appropriately
      treat such individuals who present to their clinics.

PMID- 18343329
TI  - Burning mouth syndrome: recognition, understanding, and management.
AB  - Burning mouth syndrome (BMS) can be a frustrating condition to the patient and
      the practitioner because the patient often experiences a continuous burning pain
      in the mouth without any apparent clinical signs, but the practitioner is unable
      to definitively diagnose symptoms even with the use of diagnostic testing or
      imaging. To overcome this dilemma, it is important for the practitioner to
      recognize and understand the complexities of BMS. The practitioner can then
      develop a sound approach to management of this condition and patients can be
      educated and reassured regarding BMS.

PMID- 18343330
TI  - Orofacial movement disorders.
AB  - This article reviews three poorly recognized yet relatively common presentations
      of hyperactive orofacial movement disorders: oromandibular dystonia, orofacial
      dyskinesia, and drug-induced extrapyramidal syndrome reactions. Orofacial
      movement disorders are often misdiagnosed as temporomandibular disorders, hence
      understanding these conditions is pertinent for the practitioner treating
      orofacial pain. Aspects of epidemiology, etiology, pathophysiology, clinical
      presentation, and diagnosis are discussed along with treatment considerations for
      these orofacial movement disorders.

PMID- 18343331
TI  - Cancer and orofacial pain.
AB  - Orofacial pain is commonly associated with cancer and may motivate patients to
      seek care from an oral and maxillofacial surgeon. Pain may be a presenting
      symptom of primary tumors, metastatic disease, systemic cancer, or distant non
      metastasized cancer. Patients with head and neck cancer undergoing therapy may
      suffer treatment-induced complications, which are often associated with acute
      pain. Following cancer therapy, permanent changes to tissues may cause late
      effects of treatment that may result in chronic orofacial pains. Oral and
      maxillofacial surgeons should be knowledgeable regarding these orofacial pain
      presentations.

PMID- 18343332
TI  - Bletilla striata polysaccharide stimulates inducible nitric oxide synthase and
      proinflammatory cytokine expression in macrophages.
AB  - Bletilla striata, a traditional Chinese medicine, has been used for the treatment
      of alimentary canal mucosal damage, ulcers, bleeding, bruises and burns. B.
      striata polysaccharide (BSP) isolated from B. striata was found to enhance
      vascular endothelial cell (EC) proliferation and vascular endothelial growth
      factor (VEGF) expression. However, the wound healing mechanism of BSP is not well
      understood. In this study, the results show that treatment with BSP induces
      coordinate changes in inducible nitric oxide synthase (iNOS), tumor necrosis
      factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta) mRNA levels and
      enhances the expression of these cytokines, but has no effect on interferon gamma
      (IFN-gamma) level. In this study, we partially elucidate the wound healing
      mechanism of BSP.

PMID- 18343333
TI  - Strategies for reducing supplemental medium cost in bioethanol production from
      waste house wood hydrolysate by ethanologenic Escherichia coli: inoculum size
      increase and coculture with Saccharomyces cerevisiae.
AB  - In this paper, we report a simultaneous realization of both efficient ethanol
      production and saving medium nutrient (corn steep liquor [CSL]) during bioethanol
      fermentation of overliming-treated hydrolysate of waste house wood (WHW) using
      ethanologenic Escherichia coli KO11. In cultivation using WHW hydrolysate
      supplemented with 4% (v/v) CSL and 0.2 g-dry cell weight (DCW)/l E. coli KO11
      cells, the overall ethanol yield reached 84% of the theoretical value at 61 h.
      When we conducted the cultivation with 1% CSL to reduce the supplemental medium
      cost, the overall ethanol yield remained in the range of 66-72% even at 90 h. We
      proposed two alternative methods for increasing the overall yield even with 1%
      CSL. The first method involved increasing the inoculum size of E. coli KO11 up to
      0.8 g-DCW/l, where 83% of the overall yield was attained at 60 h of cultivation.
      The second method involved the coculture of 0.2 g-DCW/l E. coli KO11 together
      with 0.02 g-DCW/l of Saccharomyces cerevisiae TJ1, and the overall yield reached
      81% at 47 h of cultivation.

PMID- 18343334
TI  - Xylitol production from rice straw hemicellulose hydrolyzate by polyacrylic
      hydrogel thin films with immobilized Candida subtropicalis WF79.
AB  - Xylose from rice straw hemicellulose hydrolysate was fermented for xylitol
      production using Candida subtropicalis WF79 cells immobilized in polyacrylic
      hydrogel thin films of 200 mum thickness. Cell immobilization was conducted by
      first suspending the yeast cells in a mixture of 2-hydroxyethyl methacrylate
      (HEMA, hydrophilic monomer), polyethylene glycol diacrylate (PEG-DA, crosslinking
      agent), and benzoin isopropyl ether (photoinitiator). The mixture was then
      allowed to form polyacrylic hydrogel thin films, between two pieces of glass
      sheets, by UV-initiated photopolymerization. The hemicellulose of rice straw was
      hydrolyzed using dilute sulfuric acid at 126 degrees C. The hydrolysate was
      neutralized with calcium hydroxide. After separating the solid residues and
      calcium sulfate precipitates by filtration, the hydrolysate was treated with
      charcoal to partially remove potential inhibitory substances, followed by vacuum
      concentration to obtain solutions of desired xylose concentrations for yeast
      fermentation. The thin films with immobilized yeast cells were submerged in the
      xylose solution from rice straw hydrolysate for fermentation in an Erlenmeyer
      flask. The maximum yield was 0.73 g of xylitol per gram of xylose consumed. In
      the 52.5-day long durability test, after 40 d of repeated batchwise operation,
      the fermentation activities of the cell immobilized in thin films began to
      decline to a yield of 0.57 g/g at the end.

PMID- 18343335
TI  - Monitoring calcium concentration in neurons with cameleon.
AB  - The calcium ion, a second messenger in the brain, plays key roles in neuronal
      signaling pathways. Ca(2+) signals in neurons are often highly localized and
      difficult to measure accurately. The quantification of calcium concentration is
      thus critical for understanding neuronal signaling. In this study, a yellow
      cameleon (YC3.60) excited using a 458 nm laser was used to monitor the calcium
      signals in neurons, and the dynamic range (R(max)/R(min)) of YC3.60 was found to
      reach 250%. The spatial distribution of calcium and the physiological changes in
      hippocampal neurons and even in spines were determined by the fluorescence
      resonance energy transfer (FRET) method. It was proved that cameleon could be
      used for the quantitative measurement of calcium concentration in neurons.
      Fluorescence readout of the calcium concentration in neurons by FRET is
      nondestructive, quantifiable with high spatiotemporal resolution, and even
      applicable to dendritic spines.

PMID- 18343336
TI  - Properties of Rhodotorula gracilis D-amino acid oxidase immobilized on magnetic
      beads through his-tag.
AB  - D-amino acid oxidase catalyzes one of the key steps in the production of
      semisynthetic cephalosporins. We expressed and purified recombinant Rhodotorula
      gracilis D-amino acid oxidase with C-terminal his-tags. This engineered enzyme
      was immobilized onto Ni(2+)-chelated nitrilotriacetic acid magnetic beads through
      the interaction between his-tag and Ni(2+). The kinetic constants, storage
      properties, and the reusability of the immobilized d-amino acid oxidase were
      determined. The effects of temperature, pH, and hydrogen peroxide on the activity
      of immobilized d-amino acid oxidase were also studied. The highest activity
      recovery was 75%. Thermal stability was improved after immobilization; the
      relative activity of the immobilized enzyme was 56% whereas the free enzyme was
      completely inactivated after incubation at 50 degrees C for 1 h. In the presence
      of 10 mM hydrogen peroxide, the immobilized enzyme did not show a rapid loss of
      activity during the first 2 h of incubation, which was observed in the case of
      the free enzyme; the residual activity of the immobilized enzyme after 9 h was
      72% compared with 22% of the free form. The long-term storage stability was
      improved; the residual activity of the immobilized enzyme was 74% compared with
      20% of the free enzyme when stored at room temperature for 10 d. The immobilized
      form retained 37% of its initial activity after 20 consecutive reaction cycles.

PMID- 18343337
TI  - Bidirectional cell-surface anchoring function of C-terminal repeat region of
      peptidoglycan hydrolase of Lactococcus lactis IL1403.
AB  - With the aim of constructing an efficient protein display system for lactic acid
      bacteria (LABs), the effect of fusion direction on the cell-surface binding
      activity of the C-terminal region of the peptidoglycan hydrolase (CPH) of
      Lactococcus lactis IL1403 was studied. CPH fused to the alpha-amylase (AMY) of
      Streptococcus bovis 148 either at its C-terminus (CPH-AMY) or at its N-terminus
      (AMY-CPH) was expressed intracellularly in Escherichia coli. This domain was able
      to direct binding of AMY to the surface of L. lactis ATCC 19435 in both
      constructs. However, the number of bound molecules per cell and the specific
      activity for starch digestion in the case of CPH-AMY were 3 and 14 times greater
      than those in the case of AMY-CPH, respectively. Of the LABs tested, L. lactis
      ATCC 19435 showed the highest binding capability for CPH-AMY, up to 6 x 10(4)
      molecules per cell, with a dissociation rate constant of 5.00 x 10(-5) s(-1). The
      binding of CPH-AMY to the surface of Lactobacillus delbrueckii ATCC 9649 cells
      was very stable with a dissociation rate constant of 6.96 x 10(-6) s(-1). The
      production of CPH-AMY in the soluble form increased 3-fold as a result of
      coexpression with a molecular chaperone, trigger factor. The results of this
      study suggest the usefulness of CPH as a bidirectional anchor protein for the
      production of cell-surface adhesive enzymes in E. coli. Furthermore, the
      importance of the fusion direction of CPH in determining cell-surface binding and
      enzymatic activities was shown.

PMID- 18343338
TI  - Inducing chondrogenic differentiation in injectable hydrogels embedded with
      rabbit chondrocytes and growth factor for neocartilage formation.
AB  - A thermoreversible hydrogel of poly(NiPAAm-co-AAc) was used as an injectable cell
      and growth factor delivery carrier for cartilage tissue engineering. Rabbit
      chondrocytes were embedded in composite hydrogels coencapsulated with
      transforming growth factor beta3 (TGFbeta3). Hydrogel constructs consisting of
      embedded cells encapsulated by the thermoreversible hydrogel served as controls
      to assess the effects of TGFbeta3 on chondrogenic differentiation. The hydrogel
      constructs were injected subcutaneously into nude mice and then monitored for up
      to 8 weeks after injection. After 8 weeks of implantation, the engineered
      cartilage acquired normal histological and biochemical properties. These results
      highlight the potential of growth factor in a hydrogel embedded with chondrocytes
      as a candidate material for neocartilage formation.

PMID- 18343339
TI  - Two-dimensional DNA gel electrophoresis mapping: a novel approach to diversity
      analysis of bacterial communities in environmental soil.
AB  - The diversity analysis of bacteria is useful for the environmental assessment of
      soil. Traditional molecular-based methods such as denaturing gradient gel
      electrophoresis (DGGE) and terminal restriction fragment length polymorphism (T
      RFLP) analysis achieve a low-resolution display of bacterial DNA fragments on a
      gel. To improve the resolution, a novel two-dimensional DNA gel electrophoresis
      (2-DGE) method was designed. This method can generate a high-resolution DNA map
      that facilitates the detailed analysis of soil bacteria. This map can be obtained
      by utilizing 2-DGE to separate genomic DNA fragments produced by polymerase chain
      reaction (PCR) amplification on the basis of chain length and G+C content. To
      develop this 2-DGE method further and to apply it to the assessment of bacterial
      diversity, we carried out a 2-DGE mapping of bacterial DNA fragments from
      different environmental soils and computed Shannon index as well as plotted rank
      abundance curves on the basis of the relative intensity of each spot on the maps.
      DGGE mapping was also performed to compare the resolution of the two methods. 2
      DGE mapping was capable of generating a higher resolution display by a factor of
      more than 2 using a DGGE fingerprint pattern on a piece of gel. Furthermore, the
      higher number of detected spots from the 2-DGE map enabled the assessment of
      differences in bacterial diversity in complex soil systems using a logarithmic
      normal rank-abundance plot.

PMID- 18343340
TI  - Expression of C-terminal repeat region of peptidoglycan hydrolase of Lactococcus
      lactis IL1403 in methylotrophic yeast Pichia pastoris.
AB  - The C-terminal region of the peptidoglycan hydrolase (CPH) of Lactococcus lactis
      IL1403 produced intracellularly in Escherichia coli was able to attach to the
      surface of cells of Lactobacillus casei NRRL B-441, Bacillus subtilis 168, E.
      coli XL1-blue and Saccharomyces cerevisiae IFO0216. Therefore, this domain is a
      suitable fusion partner for the adhesion of proteins to cell surfaces. The
      production of cell-surface adhesive proteins using this domain in Pichia pastoris
      is particularly attractive, because this organism has better capability to allow
      the correct folding of the recombinant proteins than prokaryotic hosts. However,
      when this domain is produced in this yeast, its cell-surface binding activity may
      be limited by glycosylation. In this study, therefore, we constructed a CPH
      mutant (CPHM) devoid of the potential N-glycosylation sites by site-directed
      mutagenesis. CPHM was successfully expressed extracellularly in P. pastoris
      (GS115) using the methanol inducible AOX1 promoter with an alpha-mating factor
      signal sequence, whereas the native CPH was not produced in this host. Western
      blot analysis revealed that the apparent molecular size of CPHM was 18 kDa
      greater than that of CPH produced in E. coli (32 kDa), which is attributed to O
      glycosylation. However, CPHM produced in P. pastoris was capable of binding to
      the cell surfaces despite its modification by the yeast, and its dissociation
      rate constant from the surface of L. casei NRRL B-441 cells was 3.5-fold lower
      than that of CPH produced in E. coli. These results demonstrate the applicability
      of the constructed domain (CPHM) for the production of cell-surface adhesive
      proteins in P. pastoris.

PMID- 18343341
TI  - Exogenous hormones affecting morphology and biosynthetic potential of hairy root
      line (LYR2i) of Linum album.
AB  - A hairy root line of Linum album LYR2i was obtained via the genetic
      transformation of a cotyledon segment of the plant by cocultivating it with
      Agrobacterium rhizogenes and culturing it in hormone-free B5 Gamborg liquid
      medium. Characteristic changes in root morphology associated with variations in
      biosynthetic capabilities were achieved by adding different combinations of
      phytohormones to the basal medium. A reversible system between hairy roots and
      its cultures with a diversified morphology was established by including and
      excluding phytohormones in the basal medium. The medium containing indole 3
      acetic acid (IAA) at a concentration of 3 mg/l (MI3) induced thicker root tips
      and that containing 2,4-dichlorophenoxy acetic acid (2,4-D) at a concentration of
      1 mg/l (MD1) induced compact green callus. Podophyllotoxin and 6
      methoxypodophyllotoxin content increased by 1.86-fold and 1.45-fold as a result
      of adding IAA (MI3) and 2,4-D (MD1) to the basal medium, respectively. After
      regeneration, the hairy roots regained their original morphology and biosynthetic
      capability on hormone-free basal medium. The transformation status of the
      regenerated hairy roots was confirmed by PCR analysis.

PMID- 18343342
TI  - Cloning and expression of soluble cytochrome c and its role in polyvinyl alcohol
      degradation by polyvinyl alcohol-utilizing Sphingopyxis sp. strain 113P3.
AB  - The gene encoding cytocrome c in the pva operon of Sphingopyxis sp. strain 113P3
      was cloned, on the basis of the sequence of the gene for cytochrome c (GenBank
      accession no. AB190288). The deduced amino acid sequence of the gene showed
      homologies (37% and 47% identities) with two cytochromes c of different origins.
      The recombinant cytochrome c tagged with hexahistidines was expressed in the
      periplasm of Escherichia coli BL21(DE3) harboring pT-GroE, which was in
      accordance with the localization of cytochrome c in strain 113P3; the protein was
      purified to homogeneity. The purified recombinant cytochrome c was a monomeric
      protein with a molecular weight of 16.5 kDa. The oxidized and reduced forms of
      the protein showed absorption maxima at 409 nm and at 414, 520 and 550 nm,
      respectively. The recombinant cytochrome c was fully reduced by polyvinyl alcohol
      (PVA), coupled with a catalytic amount (1/10 molar concentration) of the
      recombinant PVA dehydrogenase (PVADH) of the same origin, suggesting that the
      cytochrome c involved in the pva operon is a physiological primary electron
      acceptor for PVADH and that PVA dehydrogenation is linked with the respiratory
      chain in Sphingopyxis sp. strain 113P3.

PMID- 18343343
TI  - Analysis of selective production of Nalpha-benzyloxycarbonyl-L-aminoadipate-delta
      semialdehyde and Nalpha-benzyloxycarbonyl-L-aminoadipic acid by Rhodococcus sp.
      AIU Z-35-1.
AB  - The factors for selective production of N(alpha)-benzyloxycarbonyl-L-aminoadipate
      delta-semialdehyde (N(alpha)-Z-L-AASA) and N(alpha)-benzyloxycarbonyl-L
      aminoadipic acid (N(alpha)-Z-L-AAA) from N(alpha)-benzyloxycarbonyl-L-lysine
      (N(alpha)-Z-L-lysine) by Rhodococcus sp. AIU Z-35-1 were analyzed. The
      cultivation time was important for selective production of N(alpha)-Z-L-AASA,
      since N(alpha)-Z-L-lysine oxidizing enzyme reached maximum at the early stage of
      cell growth and then decreased. The differences of enzyme activities of N(alpha)
      Z-L-lysine oxidizing enzyme and N(alpha)-Z-L-AASA dehydrogenase in pH and
      temperature also affected the selective production of N(alpha)-Z-L-AASA. For
      efficient production of N(alpha)-Z-L-AAA, it was important for cultivation time
      that N(alpha)-Z-L-AASA dehydrogenase activity be higher than N(alpha)-Z-L-lysine
      oxidizing enzyme activity, since a high concentration of N(alpha)-Z-L-AASA
      inhibited N(alpha)-Z-L-AASA dehydrogenase activity. The optimum pH of N(alpha)-Z
      L-AAA production was affected by the instability of N(alpha)-Z-L-AASA
      dehydrogenase in the alkaline pH region.

PMID- 18343344
TI  - Efficient microbial degradation of bisphenol A in the presence of activated
      carbon.
AB  - The biodegradation of bisphenol A (BPA) was carried out with Sphingomonas sp.
      strain BP-7 and Sphingomonas yanoikuyae BP-11R in the presence of activated
      carbon (AC). When AC was present, both BPA-degrading bacteria efficiently
      degraded 300 mg/l BPA without releasing 4-hydroxyacetophenone, the major
      intermediate produced in BPA degradation, into the medium. The biological
      regeneration of AC was possible using the BPA-degrading bacteria, suggesting that
      an efficient system for BPA removal can be constructed by introducing BPA
      degrading bacteria into an AC treatment system.

PMID- 18343345
TI  - Optimization of growth conditions of Lentinus edodes mycelium on corn processing
      waste using response surface analysis.
AB  - This research was conducted to evaluate the use of corn processing waste as an
      alternative growth medium for the cultivation of Lentinus edodes mycelium and to
      determine the optimum growth conditions under solid-state cultivation. The
      substrate concentration, pH, and temperature for maximizing the growth rate of L.
      edodes mycelium, 9.3+/-0.6 mm/d, were 44.3 g/l, 4.7, and 24.7 degrees C,
      respectively. Therefore, the results suggest that corn processing waste can be
      utilized as a growth substrate for cultivating L. edodes mycelium.

PMID- 18343346
TI  - Augmentation of polysialic acid by valproic acid in early postnatal mouse
      hippocampus and primary cultured hippocampal neurons.
AB  - We examined the effects of valproic acid (VPA) on hippocampal neurons. Prenatal
      VPA exposure significantly increased polysialic acid (PSA) expression in the
      early postnatal mouse hippocampus. Moreover, VPA treatment significantly enhanced
      PSA expression in primary cultured hippocampal neurons and stimulated neurite
      growth. Our results suggest that VPA exposure in ovo affects hippocampal
      development.

PMID- 18343347
TI  - Modeling and experimental analyses reveal a two-domain structure and amino acids
      important for the activity of aminoglycoside resistance methyltransferase Sgm.
AB  - Methyltransferases that carry out posttranscriptional N7-methylation of G1405 in
      16S rRNA confer bacterial resistance to aminoglycoside antibiotics, including
      kanamycin and gentamicin. Genes encoding enzymes from this family (hereafter
      referred to as Arm, for aminoglycoside resistance methyltransferases) have been
      recently found to spread by horizontal gene transfer between various human
      pathogens. The knowledge of the Arm protein structure would lay the groundwork
      for the development of potential resistance inhibitors, which could be used to
      restore the potential of aminoglycosides to act against the resistant pathogens.
      We analyzed the sequence-function relationships of Sgm MTase, a member of the Arm
      family, by limited proteolysis and site-directed and random mutagenesis. We also
      modeled the structure of Sgm using bioinformatics techniques and used the model
      to provide a structural context for experimental results. We found that Sgm
      comprises two domains and we characterized a number of functionally compromised
      point mutants with substitutions of invariant or conserved residues. Our study
      provides a low-resolution (residue-level) model of sequence-structure-function
      relationships in the Arm family of enzymes and reveals the cofactor-binding and
      substrate-binding sites. These functional regions will be prime targets for
      further experimental and theoretical studies aimed at defining the reaction
      mechanism of m7 G1405 methylation, increasing the resolution of the model and
      developing Arm-specific inhibitors.

PMID- 18343348
TI  - Application of Toxocara canis excretory-secretory antigens and IgG subclass
      antibodies (IgG1-4) in serodiagnostic assays of human toxocariasis.
AB  - A major problem in the serodiagnosis of human toxocariasis in tropical countries
      is cross-reaction with antibodies to other helminthic diseases and a lack of
      sensitivity. The majority of tests currently available use total IgG and, in this
      study, the use of peroxidase-conjugated anti-human IgG subclass antibodies (IgG1
      4) was compared with total IgG for the diagnosis of human toxocariasis by using
      Toxocara excretory-secretory (TES) antigens in an enzyme-linked immunosorbent
      assay (ELISA) format. All four IgG subclass antibodies gave approximately 10-fold
      increases in optical density (OD) values for 50 toxocariasis patients compared to
      29 healthy normals; this was significantly greater than the approximate doubling
      of OD values seen in the total IgG-ELISA format. IgG2 gave by far the greatest
      sensitivity (values: IgG, 50%; IgG1, 60%; IgG2, 98%; IgG3, 78%; IgG4, 64%).
      Significant cross-reactivity using all IgG subclasses in the TES ELISA was seen
      with 141 serum samples from patients with 10 other helminthic infections.
      However, IgG3 gave the best specificity (values: IgG, 73%; IgG1, 76%; IgG2, 71%;
      IgG3, 81%; IgG4, 71%). Thus, of the IgG subclass antibodies, IgG2 appeared best
      and employing this subclass can improve the serodiagnosis of human toxocariasis
      since it recognises carbohydrate epitopes of TES antigens.

PMID- 18343349
TI  - Spectral-domain Cirrus high-definition optical coherence tomography is better
      than time-domain Stratus optical coherence tomography for evaluation of macular
      pathologic features in uveitis.
AB  - PURPOSE: To compare high-definition (HD) spectral-domain optical coherence
      tomography [SD-OCT] (Cirrus HD-OCT; Carl Zeiss, Dublin, California, USA) with
      time-domain optical coherence tomography [TD-OCT] (Stratus version 4; Carl Zeiss)
      for imaging macula in patients of uveitis. DESIGN: Interventional case series.
      METHODS: Thirty consecutive patients (51 eyes) with uveitis of various causes
      with vitreous haze of 1+ or worse were treated in an institutional setting. All
      patients had their vitreous haze graded and OCT scans both on TD-OCT (Stratus)
      and SD-OCT (Cirrus). Information obtained from Cirrus OCT scans was compared with
      that obtained from Stratus OCT scans. RESULTS: Overall, for all grades of media
      clarity, the macula was interpreted as normal in 30 eyes (58.8%) on Stratus OCT
      and 26 eyes (50.9%) on Cirrus OCT and abnormal in 15 eyes (29.4%) on Stratus OCT
      and 24 eyes (47.0%) on Cirrus OCT, whereas poor scan quality deterred any
      interpretation in six eyes (10.0%) on Stratus OCT and only in one eye (1.8%) on
      Cirrus OCT. Additional information on Cirrus OCT could be obtained in nine
      (21.9%) of 41 eyes with grade 1+ vitreous haze, six (75%) of eight eyes with
      grade 2+ vitreous haze, and one eye (50%) with vitreous haze of 3+. CONCLUSIONS:
      Our preliminary results suggest that SD Cirrus HD-OCT has an advantage over TD
      Stratus OCT in uveitic eyes by providing better identification of normal and
      pathologic structure in patients with poor media clarity.

PMID- 18343350
TI  - A fluidics comparison of Alcon Infiniti, Bausch & Lomb Stellaris, and Advanced
      Medical Optics Signature phacoemulsification machines.
AB  - PURPOSE: To compare three phacoemulsification machines for measurement accuracy
      and postocclusion surge (POS) in human cadaver eyes. DESIGN: In vitro comparisons
      of machine accuracy and POS. METHODS: Tip vacuum and flow were compared with
      machine indicated vacuum and flow. All machines were placed in two human cadaver
      eyes and POS was determined. RESULTS: Vacuum (% of actual) was 101.9% +/- 1.7%
      for Infiniti (Alcon, Fort Worth, Texas, USA), 93.2% +/- 3.9% for Stellaris
      (Bausch & Lomb, Rochester, New York, USA), and 107.8% +/- 4.6% for Signature
      (Advanced Medical Optics, Santa, Ana, California, USA; P < .0001). At 60
      ml/minute flow, actual flow and unoccluded flow vacuum (UFV) was 55.8 +/- 0.4
      ml/minute and 197.7 +/- 0.7 mm Hg for Infiniti, 53.5 +/- 0.0 ml/minute and 179.8
      +/- 0.9 mm Hg for Stellaris, and 58.5 +/- 0.0 ml/minute and 115.1 +/- 2.3 mm Hg
      for Signature (P < .0001). POS in an 32-year-old eye was 0.33 +/- 0.05 mm for
      Infiniti, 0.16 +/- 0.06 mm for Stellaris, and 0.13 +/- 0.04 mm for Signature at
      550 mm Hg, 60 cm bottle height, 45 ml/minute flow with 19-gauge tips (P < .0001
      for Infiniti vs Stellaris and Signature). POS in an 81-year-old eye was 1.51 +/-
      0.22 mm for Infiniti, 0.83 +/- 0.06 mm for Stellaris, 0.67 +/- 0.01 mm for
      Signature at 400 mm Hg vacuum, 70 cm bottle height, 40 ml/minute flow with 19
      gauge tips (P < .0001). CONCLUSIONS: Machine-indicated accuracy, POS, and UFV
      were statistically significantly different. Signature had the lowest POS and
      vacuum to maintain flow. Regarding POS, Stellaris was close to Signature;
      regarding vacuum to maintain flow, Infiniti and Stellaris were similar.
      Minimizing POS and vacuum to maintain flow potentially are important in avoiding
      ocular damage and surgical complications.

PMID- 18343351
TI  - Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis.
AB  - PURPOSE: Toxoplasmic retinochoroiditis is thought to recur randomly. We sought to
      determine whether there is, instead, a longitudinal pattern of recurrences and to
      identify risk factors for recurrence. DESIGN: Longitudinal cohort study. METHODS:
      We collected the following data for 143 patients with toxoplasmic
      retinochoroiditis in The Netherlands: gender, first affected eye, age at first
      episode, mode of Toxoplasma gondii infection (congenital vs postnatal), treatment
      history, and presence of retinal scars at initial examination. For each episode,
      we determined age, duration since first episode, and interval since previous
      episode. We estimated the relationship between disease-free interval after an
      episode and recurrence risk. The influence of host and disease factors on
      recurrence risk was analyzed using Cox regression with frailty modeling for
      correlated intrapatient recurrence times. We performed a Monte Carlo test for
      occurrence of clusters after prolonged disease-free intervals. RESULTS: Follow-up
      ranged from 0.3 to 41 years (323 episodes in first-affected eyes). Recurrence
      risk was highest immediately after an episode, then decreased with increasing
      disease-free intervals, a pattern consistent with clustering. Relative risk (RR)
      of recurrence declined 72% (RR, 0.28; 95% confidence interval [CI], 0.22 to 0.36;
      P < .001) with each 10-year interval since first episode, and declined 15% (RR,
      0.85; 95% CI, 0.71 to 1.01; P = .06) for each 10-year increase in age at first
      episode. Patients more than 40 years of age were at higher risk of recurrence
      than younger patients (RR, 1.74; 95% CI, 1.06 to 2.86; P = .03). Clusters of
      episodes occurred after prolonged disease-free intervals. CONCLUSIONS:
      Toxoplasmic retinochoroiditis occurs in clusters over time. Recurrence risk is
      influenced by patient age and duration of infection.

PMID- 18343352
TI  - Effect of tensile force on expression of PTHrP and thickness of hypertrophic zone
      in organ-cultured mouse spheno-occipital synchondroses.
AB  - OBJECTIVE: Responses of spheno-occipital synchondroses to direct tensile stress
      have not been identified before. This study was, therefore designed to evaluate
      expression of PTHrP, and thickness of hypertrophic zone in spheno-occipital
      synchondroses in response to such stress, using mouse in vitro model. METHODS:
      Spheno-occipital synchondroses together with adjacent structures were excised
      from fifty-five 2-day-old mice that were randomly assigned to 6 control and 5
      experimental groups for 5 experimental periods (n=5). In the experimental groups,
      tensile force of 0.2g was applied across the synchondroses, using helical
      springs. In 5 control groups, the springs were made inactive. Both groups were
      then cultured for 6, 24, 48, 72 h and 7 days. Another control group was cultured
      without any springs for 7 days to compare with natural growth of the
      synchondroses from a group of five 9-day-old mice. Alcian blue-PAS staining was
      used to study growth of the synchondroses; immunohistochemical staining to
      identify PTHrP and type X collagen expression. The area of PTHrP expression and
      thickness of hypertrophic zone, demarcated by type X collagen expression, were
      measured. RESULTS: Quantitative analysis showed that PTHrP expression increased
      significantly at hour 24 of the force application in the experimental group
      (p<0.05), then reduced from hour 24 to 72 with a significant drop from hour 24 to
      48 (p<0.01); and the thickness of hypertrophic zone significantly increased at
      hour 48 (p<0.01). CONCLUSIONS: Our findings suggested that the growth of spheno
      occipital synchondroses could be modified by tensile stress; and a light
      continuous force could enhance its growth, as evidenced by an increase in PTHrP
      expression and thickness of hypertrophic zone.

PMID- 18343353
TI  - Oxytocin enhances the encoding of positive social memories in humans.
AB  - BACKGROUND: In nonhuman mammals, oxytocin has a critical role in social
      recognition and the development of long-term bonds. There has been limited
      research evaluating effects of oxytocin on the encoding and recognition of faces
      in humans. METHODS: In a double-blind, randomized, placebo-controlled, between
      subject design, we administered oxytocin (24 IU) or a placebo to 69 healthy human
      male volunteers and then presented 36 happy, angry, or neutral human faces.
      Participants returned the following day to make "remember," "know," or "new"
      judgments for a mix of 72 new and previously seen faces. RESULTS: Oxytocin
      administered participants were more likely to make remember and know judgments
      for previously seen happy faces compared with angry and neutral human faces. In
      contrast, oxytocin did not influence judgments for faces that had not been
      presented previously. CONCLUSIONS: This study shows that the administration of
      oxytocin to male humans enhances the encoding of positive social information to
      make it more memorable. Results suggest that oxytocin could enhance social
      approach, intimacy, and bonding in male humans by strengthening encoding to make
      the recall of positive social information more likely.

PMID- 18343354
TI  - Platelet membrane fluidity and Na+/K+ ATPase activity in acute stroke.
AB  - Stroke is a consequence of a reduction in cerebral blood flow but the mechanisms
      involved in the production of ischemic damage are complex and probably not fully
      known. It is hypothesized that alterations in platelet membrane fluidity are
      directly related to the severity of the stroke as measured by the National
      Institute of Health Stroke Scale (NIHSS). Thus, the aim of the present study was
      to investigate Na+/K+ ATPase activity and platelet membrane fluidity, measured by
      fluorescent probes TMA-DPH and DPH in patients affected by ischemic stroke and
      controls in order to identify, if any, chemical-physical and/or functional
      modifications associated with cerebral ischemic damage. Patients were divided
      into three groups according to the presence of vascular risk factors (Diabetes
      Mellitus, Hypertension and Smoking) in order to evaluate the possible influence
      of each risk factor on the NIHSS score and both Na+/K+ ATPase activity and
      platelet membrane fluidity. Data showed a significant decrease in both Na+/K+
      ATPase activity and platelet fluidity values in patients compared to controls.
      Moreover, all three groups showed a negative significant correlation between
      NIHSS and Na+/K+ ATPase activity and a positive significant correlation between
      NIHSS, TMA-DPH and DPH. In conclusion, the present data point out that
      alterations in the platelet membrane's chemical-physical (decreased fluidity) and
      functional properties (reduced Na+/K+ ATPase activity) rose proportionally with
      NIHSS increase. These modifications and their interaction with some vascular risk
      factors might be involved in the pathogenesis of ischemic damage development.

PMID- 18343355
TI  - Role of histamine in brain protection in surgical brain injury in mice.
AB  - Surgical resection of brain tissue is associated with tissue damage at the
      resection margin. Studies of ischemic brain injury in rodents have shown that
      administration of L-histidine and thioperamide reduces ischemic tissue loss, in
      part by inhibition of apoptotic cell death. In this study we tested
      administration of L-histidine and thioperamide in surgical brain injury in mice.
      Mice were randomized to one of three groups: Sham surgery (n=18), surgical brain
      injury without treatment (SBI) (n=33), and surgical brain injury with combined l
      histidine and thioperamide treatment (SBI+H) (n=29). Surgical brain injury was
      induced via right frontal craniotomy with resection of the right frontal lobe. L
      histidine (1000 mg/kg) and thioperamide (5 mg/kg) were administered to the SBI+H
      group immediately following surgical resection. Postoperative assessment included
      neurobehavioral scores, Evans blue measurement of blood-brain barrier breakdown,
      brain water content, Nissl histology, and immunohistochemistry for IgG and
      cleaved caspase 3. Postoperative findings included equivalent neurobehavioral
      outcomes at 24 and 72 h in the SBI and SBI+H groups, similar histological
      outcomes between SBI and SBI+H, and similar qualitative staining for cleaved
      caspase 3. SBI+H had increased BBB breakdown on Evans blue analysis and a trend
      towards increased brain edema which was significant at 72 h. We conclude that
      combined treatment with l-histidine and thioperamide leads to increased BBB
      breakdown and brain edema in surgical brain injury.

PMID- 18343356
TI  - Differential and dose-dependent regulation of gene expression at the mid
      hindbrain boundary by Ras-MAP kinase signaling.
AB  - Recent experiments suggest that activation of the Ras-MAP kinase pathway at the
      mid-hindbrain boundary (MHB) induces cerebellar development, whereas tectal
      development occurs in the absence of Ras-MAP kinase activity. To test this model
      we have stimulated or inhibited Ras-MAP kinase signaling in chick embryos through
      targeted misexpression of a constitutive active (Ras(V12)) or dominant negative
      (Ras(N17)) form of Ras. The consequence of these manipulations on the expression
      of several genes that are expressed in distinct patterns at or around the MHB
      organizer, including En1, Pax2, Pax3, Pax5, Wnt1, Meis2, and ephrin-A2, -A5, and 
      B1, was assessed. Extending previous findings we show that inhibition of Ras-MAP
      kinase signaling differently affects Pax3 expression in different regions of the
      mid-hindbrain territory, inhibiting its expression in the midbrain but inducing
      it in the MHB region. Expression of the midbrain specific marker gene Meis2 was
      not affected by Ras(N17) at first but later upregulated concomitantly with the
      morphological transformation of hindbrain to midbrain. In addition, we show that
      different dosages of Ras-MAP kinase activity are required for transcriptional
      activation of Wnt1 and En1 at the MHB. Collectively, these results validate and
      extend previous findings on the molecular changes associated with Fgf8 loss-of
      function or gain-of-function phenotypes at the MHB, demonstrate that gene
      expression at the MHB is regulated by Ras-MAP kinase signaling in a spatially and
      temporally distinct manner and provide evidence for a dosage dependent function
      of Fgf8 signaling at the MHB.

PMID- 18343357
TI  - Effects of omni-directional noise-exposure during hearing onset and age on
      auditory spatial resolution in the Mongolian gerbil (Meriones unguiculatus) -- a
      behavioral approach.
AB  - Inhibitory inputs to the binaural brainstem nuclei medial and lateral superior
      olives (MSO and LSO, respectively) are thought to be important for sound
      localization in mammals. Here, we investigate whether aged gerbils that typically
      exhibit degenerative changes in auditory nuclei providing inhibition to MSO and
      LSO show diminished localization ability. We also tested the localization ability
      in gerbils reared in omni-directional white noise during hearing onset, a
      treatment that affects the adjustment of inhibitory inputs to MSO neurons
      possibly resulting in weakened sensitivity to interaural time difference.
      Localization ability of both groups was compared to that of young gerbils raised
      under control conditions. Stimuli had a duration of 125 ms and were pure tones of
      0.5, 1, 2, 4 and 8 kHz, 300-Hz-bands of noise centered at 0.5, 2 and 8 kHz or
      broad-band noise. Gerbils trained in a two-alternative-forced-choice procedure
      indicated if sounds were presented from the left or from the right by choosing
      the respective response compartment of a Y-shaped experimental setup. The minimum
      resolvable angle (MRA) was calculated as the minimum angle between two
      loudspeaker locations that a gerbil was able to discriminate. MRAs for aged
      gerbils were higher compared to controls, whereas MRAs of noise-reared gerbils
      did not differ from those of the control group. Results are discussed with
      respect to the progressive degeneration affecting the gerbil's auditory system,
      changes in the anatomical arrangement of inhibitory inputs on binaural neurons in
      the MSO, and hearing thresholds.

PMID- 18343358
TI  - Entrainment of temperature and activity rhythms to restricted feeding in orexin
      knock out mice.
AB  - Ablation of the SCN, an established circadian clock, does not abolish food
      entrainment, suggesting that the food-entrainable oscillator (FEO) must lie
      outside the SCN. Typically, animals show anticipatory locomotor activity and rise
      in core body temperature under the influence of the FEO. Signals from the FEO
      would, therefore, converge onto arousal neurons so that the animal might forage
      for food. In the present study, we investigate whether the neuropeptide orexin,
      which has been linked to arousal, might transduce the arousal signal. Orexin
      knockout (orexin-KO) and wildtype (WT) mice (both C57BL/6J derived) were
      implanted with MiniMitter transmitters that recorded core body temperature and
      activity (12 h LD cycle). After a week of ad-libitum feeding, the mice were given
      access to food for 4 h (ZT 4-8) for nine days followed by 2-days of fasting. When
      orexin-KO mice were placed in a restricted feeding schedule, both core body
      temperature and activity entrained to the feeding schedule. In these mice gross
      locomotor activity was severely blunted during the nine day period of restricted
      feeding (-79.4+/-6.3%) from the WT, but they showed an increase in core body
      temperature in anticipation to the meal time similar to the WT mice. There was no
      difference in the amount of food intake between the genotypes. We conclude that
      orexin is not required for entrainment of activity and temperature to a
      restricted feeding schedule, but is required for the robust expression of gross
      locomotor activity in anticipation of the scheduled feeding.

PMID- 18343359
TI  - Influence of volume reduction and cryopreservation methodologies on quality of
      thawed umbilical cord blood units for transplantation.
AB  - INTRODUCTION: Although there is considerable variability in methodology among
      umbilical cord blood banks, their common goal is to achieve optimal product
      quality for transplantation. Cryopreservation is a critical issue for a long-term
      maintenance of cord blood viability and colony-forming capacities. MATERIALS AND
      METHODS: We designed a prospective study to compare controlled (CRF) vs. non
      controlled freezing (URF) of volume-reduced cord blood units. In addition, the
      influence of hydroxy ethyl starch (HES) on cryopreservation was also assayed. To
      assess the efficiency of protocols used, cell recoveries were measured and the
      presence of hematopoietic colony-forming units was quantified. RESULTS: In the
      study phase, we observed similar CB haematopoietc recoveries for CRF and URF
      strategies, except for TNC recovery that was better for HES volume reduced CB
      units in the URF group. When we analysed the data of routine processed CB units
      in samples from satellite cryovials, we found better BFU-E, CFU-GM, CFU-GEMM and
      CFU recoveries for those units processed with HES than without HES, in an URF
      manner. CONCLUSIONS: URF of CB units is a cryopreservation procedure that allows
      similar hematopoietic progenitor recoveries than CRF with programmed devices.
      However, our study suggests that those banks that cryopreserve CB units in a URF
      manner should use HES for volume reduction. On the other hand, for CRF
      cryopreservation methodology volume reduction with and without HES are equally
      useful.

PMID- 18343360
TI  - Complementary striped expression patterns of NK homeobox genes during segment
      formation in the annelid Platynereis.
AB  - NK genes are related pan-metazoan homeobox genes. In the fruitfly, NK genes are
      clustered and involved in patterning various mesodermal derivatives during
      embryogenesis. It was therefore suggested that the NK cluster emerged in
      evolution as an ancestral mesodermal patterning cluster. To test this hypothesis,
      we cloned and analysed the expression patterns of the homologues of NK cluster
      genes Msx, NK4, NK3, Lbx, Tlx, NK1 and NK5 in the marine annelid Platynereis
      dumerilii, a representative of trochozoans, the third great branch of bilaterian
      animals alongside deuterostomes and ecdysozoans. We found that most of these
      genes are involved, as they are in the fly, in the specification of distinct
      mesodermal derivatives, notably subsets of muscle precursors. The expression of
      the homologue of NK4/tinman in the pulsatile dorsal vessel of Platynereis
      strongly supports the hypothesis that the vertebrate heart derived from a dorsal
      vessel relocated to a ventral position by D/V axis inversion in a chordate
      ancestor. Additionally and more surprisingly, NK4, Lbx, Msx, Tlx and NK1
      orthologues are expressed in complementary sets of stripes in the ectoderm and/or
      mesoderm of forming segments, suggesting an involvement in the segment formation
      process. A potentially ancient role of the NK cluster genes in segment formation,
      unsuspected from vertebrate and fruitfly studies so far, now deserves to be
      investigated in other bilaterian species, especially non-insect arthropods and
      onychophorans.

PMID- 18343361
TI  - Dissection of a complex seed phenotype: novel insights of FUSCA3 regulated
      developmental processes.
AB  - A T-DNA insertion mutant of FUSCA3 (fus3-T) in Arabidopsis thaliana exhibits
      several of the expected deleterious effects on seed development, but not the
      formation of brown seeds, a colouration which results from the accumulation of
      large amounts of anthocyanin. A detailed phenotypic comparison between fus3-T and
      a known splice point mutant (fus3-3) revealed that the seeds from both mutants do
      not enter dormancy and can be rescued at an immature stage. Without rescue,
      mature fus3-3 seeds are non-viable, whereas those of fus3-T suffer only a slight
      loss in their germinability. A series of comparisons between the two mutants
      uncovered differences with respect to conditional lethality, in histological and
      sub-cellular features, and in the relative amounts of various storage compounds
      and metabolites present, leading to a further dissection of developmental
      processes in seeds and a partial reinterpretation of the complex seed phenotype.
      FUS3 function is now known to be restricted to the acquisition of embryo
      dependent seed dormancy, the determination of cotyledonary cell identity, and the
      synthesis and accumulation of storage compounds. Based on DNA binding studies, a
      model is presented which can explain the differences between the mutant alleles.
      The fus3-T lesion is responsible for loss of function only, while the fus3-3
      mutation induces various pleiotropic effects conditioned by a truncation gene
      product causing severe mis-differentiation.

PMID- 18343362
TI  - Corticotropin releasing factor in the median raphe nucleus is involved in the
      retrieval of fear memory in rats.
AB  - In the present study, we examined the role of corticotropin releasing factor
      (CRF) in the median raphe nucleus (MRN) on fear-related behaviors in rats. We
      employed the contextual fear conditioning test and the elevated plus maze test as
      memory-dependent and -independent tasks, respectively. Human/rat CRF (10 ng) in
      0.5 microl saline was injected into the MRN. Administration of CRF significantly
      increased memory dependent, but not independent, fear expression. These results
      suggest that CRF release in the MRN is involved in the retrieval of fear memory.

PMID- 18343363
TI  - Acute and chronic heroin dependence in mice: contribution of opioid and
      excitatory amino acid receptors.
AB  - Opioid and excitatory amino acid receptors contribute to morphine dependence, but
      there are no studies of their role in heroin dependence. Thus, mice injected with
      acute or chronic heroin doses in the present study were pretreated with one of
      the following selective antagonists: 7-benzylidenenaltrexone (BNTX), naltriben
      (NTB), nor-binaltorphimine (nor-BNI; delta1, delta2, and kappa opioid receptors,
      respectively), MK-801, or LY293558 (NMDA and AMPA excitatory amino acid
      receptors, respectively). Naloxone-precipitated withdrawal jumping frequency,
      shown here to be a reliable index of heroin dependence magnitude, was reduced by
      BNTX or NTB in mice injected with both acute and chronic heroin doses. In
      contrast, nor-BNI did not alter jumping frequencies in mice injected with an
      acute heroin dose but significantly increased them in mice receiving chronic
      heroin injections. Continuous MK-801 or LY293558 infusion, but not injection,
      reduced jumping frequencies during withdrawal from acute heroin treatment. Their
      delivery by injection was nonetheless effective against chronic heroin
      dependence, suggesting mechanisms not simply attributable to NMDA or AMPA
      blockade. These data indicate that whereas delta1, delta2, NMDA, and AMPA
      receptors enable acute and chronic heroin dependence, kappa receptor activity
      limits the dependence liability of chronic heroin. With the exception of delta1
      receptors, the apparent role of these receptors to heroin dependence is
      consistent with their contribution to morphine dependence, indicating that there
      is substantial physiological commonality underlying dependence to both heroin and
      morphine. The ability of kappa receptor blockade to differentially alter acute
      and chronic dependence supports previous assertions from studies with other
      opioids that acute and chronic opioid dependence are, at least in part,
      mechanistically distinct. Elucidating the substrates contributing to heroin
      dependence, and identifying their similarities and differences with those of
      other opioids such as morphine, may yield effective treatment strategies to the
      problem of heroin dependency.

PMID- 18343364
TI  - A novel benzotriazole derivative inhibits proliferation of human hepatocarcinoma
      cells by increasing oxidative stress concomitant mitochondrial damage.
AB  - Benzotriazole derivatives have been shown to be able to induce growth inhibition
      in cancer cells. In the present study, we synthesized bioactive compound, 3-(1H
      benzo [d] [1,2,3] triazol-1-yl)-1-(4-methoxyphenyl)-1-oxopropan-2-yl benzoate
      (BmOB), which is a novel benzotriazole derivative. BmOB displayed anti
      proliferative effects on several human tumor cell lines. Human hepatocarcinoma
      BEL-7402 cell line was selected as a model to illustrate BmOB's inhibition effect
      and its potential mechanism, since it was the highest susceptible cell line to
      BmOB. It was shown that treatment with BmOB resulted in generation of reactive
      oxygen species, disruption of mitochondrial membrane potential (DeltaPsim), and
      cell death in BEL-7402 cells. BmOB induced cytotoxicity could be prevented by
      antioxidant vitamin C and mitochondrial permeability transition inhibitor
      cyclosporine A. cyclosporine A could also protect the BmOB induced collapse of
      DeltaPsim in BEL7402 cells, while vitamin C did not show similar effects. The
      results suggest that BmOB could inhibit BEL-7402 cell proliferation, and the cell
      death may occur through the modulation of mitochondrial functions regulated by
      reactive oxygen species. It appears that collapse of DeltaPsim prior to
      intracellular reactive oxygen species arose during the cytotoxic process in our
      experimental system.

PMID- 18343365
TI  - Spisulosine (ES-285) induces prostate tumor PC-3 and LNCaP cell death by de novo
      synthesis of ceramide and PKCzeta activation.
AB  - During the past decades, intense attention has been focused on the anti-tumor
      properties of marine compounds which some of them have been revealed as potent
      apoptotic inducers. In the present work, we studied the mechanism of action of a
      new compound, Spisulosine (ES-285), isolated from the sea mollusc Spisula
      polynyma, in the prostate tumor PC-3 and LNCaP cell lines. Spisulosine inhibited
      cell proliferation with an IC50 of 1 microM in both cell lines, although it was
      more effective in the androgen-independent PC-3 cells. The anti-proliferative
      effect induced by Spisulosine in prostate cells was independent of peroxisome
      proliferator activated receptor gamma (PPARgamma) and phosphatidylinositol 3
      kinase/(PI3K/Akt), Jun N-terminal kinase (JNK), p38 or classical protein kinase C
      (PKCs) pathways, as it was inferred from the results obtained with specific
      inhibitors of these routes. However, Spisulosine treatment of prostate cells
      induced an increase in the intracellular ceramide levels, that was totally
      blocked by the ceramide synthase inhibitor Fumonisin B1, indicating that the
      ceramide accumulation came from the de novo biosynthesis. Spisulosine also
      induced in both PC-3 and LNCaP cells, an activation of the atypical PKC isoform,
      PKCzeta, which is one of the target proteins of ceramide. These results indicate
      that the marine compound Spisulosine inhibits the growth of the prostate PC-3 and
      LNCaP cells through intracellular ceramide accumulation and PKCzeta activation.

PMID- 18343366
TI  - Autophagy modulates keratin-containing inclusion formation and apoptosis in cell
      culture in a context-dependent fashion.
AB  - The major pathways for protein degradation are the proteasomal and lysosomal
      systems. Derangement of protein degradation causes the formation of intracellular
      inclusions, and apoptosis and is associated with several diseases. We utilized
      hepatocyte-derived cell lines to examine the consequences of the cytoplasmic
      hepatocyte Mallory-Denk body-like inclusions on organelle organization, autophagy
      and apoptosis, and tested the hypothesis that autophagy affects inclusion
      turnover. Proteasome inhibitors (PIs) generate keratin-containing Mallory-Denk
      body-like inclusions in cultured cells and cause reorganization of mitochondria
      and other organelles, autophagy and apoptosis. In cultured hepatoma cells,
      caspase inhibition blocks PI-induced apoptosis but not inclusion formation or
      autophagy activation. Autophagy induction by rapamycin decreases the extent of PI
      induced inclusions and apoptosis in Huh7 and OUMS29 cells. Surprisingly, blocking
      of autophagy sequestration by 3 methyl adenine or beclin 1 siRNA, but not
      bafilomycin A1 inhibition of autophagic degradation, also inhibits inclusion
      formation in the tested cells. Therefore, autophagy can be upstream of apoptosis
      and may promote or alleviate inclusion formation in cell culture in a context
      dependent manner via putative autophagy-associated molecular triggers.
      Manipulation of autophagy may offer a strategy to address the importance of
      inclusion formation and its significance in inclusion-associated diseases.

PMID- 18343367
TI  - P120-catenin is a novel desmoglein 3 interacting partner: identification of the
      p120-catenin association site of desmoglein 3.
AB  - P120-catenin (p120ctn) is an armadillo-repeat protein that directly binds to the
      intracytoplasmic domains of classical cadherins. p120ctn binding promotes the
      stabilization of cadherin complexes on the plasma membrane and thus positively
      regulates the adhesive activity of cadherins. Using co-immunoprecipitation, we
      show here that p120ctn associates to desmogleins (Dsg) 1 and 3. To determine
      which region is involved in the association between Dsg3 and p120ctn, we
      constructed mutant Dsg3 proteins, in which various cytoplasmic subdomains were
      removed. The tailless Dsg3 constructs Delta IA:AA1-641Dsg3 and Delta 641-714Dsg3,
      which do not contain the intracellular anchor (IA) region, did not coprecipitate
      with p120cn, nor did they colocalize at the plasma membrane. Immunocytochemical
      analysis revealed that p120ctn does not localize to desmosomes, but colocalizes
      with Dsg3 at the cell surface. A biotinylation assay for Dsg3 showed that
      biotinylated Delta 641-714Dsg3 was turned over more rapidly than wild-type Dsg3.
      These results indicate that the membrane proximal region (corresponding to
      residues 641-714) in the IA region of Dsg3 is necessary for complex formation
      with p120ctn, and to maintain free Dsg3 at the cell surface before it is
      integrated into desmosomes. In summary, we show that p120ctn is a novel
      interactor of the Dsg proteins, and may play a role in desmosome remodeling.

PMID- 18343368
TI  - Generation of transparency and cellular organization in lens explants.
AB  - The lens grows via the proliferation and differentiation of lens epithelial cells
      into lens fibres. This differentiation process, thought to be controlled by
      factors present in the vitreous fluid, generates tightly-packed, parallel-aligned
      fibre cells that confer transparency to the lens. Using lens epithelial-cell
      explants we examined how explant orientation and growth factor treatment can
      affect cellular arrangement and explant transparency. Fibre cell differentiation
      was induced in lens explants by culturing cells with fibroblast growth factor
      (FGF) or bovine vitreous. Cell shape and arrangement was investigated using
      confocal microscopy, electron microscopy, immunofluorescence and in situ
      hybridization. Explant transparency was measured using light microscopy. Confocal
      microscopy demonstrated that explant orientation determined cellular arrangement,
      irrespective of the differentiation stimuli used. In explants where epithelial
      cells were confined between their normal basement membrane (the lens capsule) and
      the base of the culture dish, the cells became elongated, thin and parallel
      aligned. In contrast, in explants cultured with cells directly exposed to the
      culture media the cells appeared to be shorter, globular and haphazardly
      arranged. FGF initiated the differentiation of most lens epithelial cells;
      however, abnormal cellular morphologies developed with subsequent culture of the
      cells. As a result, the transparency of these explants decreased with prolonged
      culture. Interestingly, explants cultured with vitreous (i) did not develop
      abnormal cellular morphologies, (ii) contained two distinct cell types (retained
      epithelial cells and newly differentiated fibre cells) and (iii) remained
      transparent throughout the lengthy culture period. In summary, we have developed
      a culture system that generates a transparent tissue with a cellular arrangement
      resembling that of the lens in vivo. We have shown that while FGF and vitreous
      initiate differentiation within this system, better maintenance of fibre cell
      integrity, more appropriate regulation of molecular events, and better
      maintenance of explant transparency was achieved in the presence of vitreous.
      This system offers an opportunity to further investigate the process of lens
      fibre cell differentiation as well as a means of better identifying the factors
      that contribute to the development of tissue transparency in vitro.

PMID- 18343369
TI  - Evidence supporting zoonotic transmission of Cryptosporidium in rural New South
      Wales.
AB  - Cryptosporidium hominis, which has an anthroponotic transmission cycle and
      Cryptosporidium parvum, which is zoonotic, are the primary species of
      Cryptosporidium that infect humans. The present study identified the
      species/genotypes and subgenotypes of Cryptosporidium in 7 human and 15 cattle
      cases of sporadic cryptosporidiosis in rural western NSW during the period from
      November 2005 to January 2006. The species/genotype of isolates was determined by
      PCR sequence analysis of the 18S rRNA and C. parvum and C. hominis isolates were
      subgenotyped by sequence analysis of the GP60 gene. Fourteen of 15 cattle-derived
      isolates were identified as C. parvum and 1 as a C. bovis/C. parvum mixture. Of
      the human isolates, 4 were C. parvum and 3 were C. hominis. Two different
      subgenotypes were identified with the human C. hominis isolates and six different
      subgenotypes were identified within the C. parvum species from humans and cattle.
      All four of the C. parvum subtypes found in humans were also found in the cattle,
      indicating that zoonotic transmission may be an important contributor to sporadic
      human cases cryptosporidiosis in rural NSW.

PMID- 18343370
TI  - Host species diversity and post-blood feeding carbohydrate availability enhance
      survival of females and fecundity in Aedes albopictus (Diptera: Culicidae).
AB  - Aedes albopictus mosquito is an opportunistic blood feeder and has a broad host
      range. The feeding behavior and habits of this mosquito are liable to increase
      the transmission potential of arboviruses. The survival and fecundity in A.
      albopictus fed on different hosts and post-blood meal provision of sugar were
      investigated in a laboratory-reared colony. Adult survival of caged female A.
      albopictus that were fed on blood of two different hosts (double meal) was higher
      than the females fed only on one host (single meal) (mean survival: 70.2+/-9.6
      vs. 55.5+/-5.5%, respectively) when held in the laboratory for 72 h after blood
      feeding. Mean survival of females provided 10% sucrose solution (in water) after
      a single or double blood meal was higher (90.5+/-6.4% and 89.3+/-6.5%,
      respectively) than in the respective groups receiving water only following blood
      feeding (double meal: 49.0+/-9.6%; single meal: 45.3+/-10.9%). Females receiving
      a double meal were more fecund on average (89.0+/-6.6 eggs) than females provided
      a single meal (82.3+/-8.2 eggs).

PMID- 18343371
TI  - Plasmodium falciparum: genetic polymorphism in apical membrane antigen-1 gene
      from Indian isolates.
AB  - A number of stage-specific antigens have been characterized for vaccine
      development against Plasmodium falciparum malaria. This study presents a
      comprehensive analysis of the sequence polymorphism in Plasmodium falciparum
      apical membrane antigen-1 (PfAMA-1) in population samples from the eastern and
      western parts of India. This is the first study of its kind for the nearly full
      length PfAMA-1 gene from these regions in India. Our observations confirmed that
      sequence diversity of PfAMA-1 confines only to point mutations and shows 4-8%
      variation as compared to the prototypes. As opposed to the previous studies on
      PfAMA-1, our study revealed a greater degree of polymorphism in the Domain II
      region of PfAMA-1 protein, though signature for diversifying selection is seen
      throughout the gene. Our present investigation also indicates a very high degree
      of variation in the reported T- and B-cell epitopes of PfAMA-1. Few noteworthy
      and unique observations made in this study are the substitution of Cysteine
      residues responsible for the disulfide bond structure of the protein and the
      presence of premature termination after 595 amino acids in 3 of the 13 isolates
      under consideration. These crucial findings add new perspectives to the future of
      AMA-1 research and could have major implications in establishing AMA-1 as a
      vaccine candidate.

PMID- 18343372
TI  - The effects of bee (Apis mellifera) venom phospholipase A2 on Trypanosoma brucei
      brucei and enterobacteria.
AB  - The potential role of phospholipases in trypanosomiasis was investigated using
      bee venom phospholipase A2 (bvPLA2) as a model. The effects of bvPLA2 on the
      survival of Trypanosoma brucei brucei, 2h and 12h cultures of Enterobacter
      cloacae, Escherichia coli, Citrobacter freundii were studied. About 1 mg ml(-1)
      bvPLA2 was trypanocidal after 30 min. Some growth occurred at lower
      concentrations up to 2h after treatment but viability decreased up to 8h. Even
      very low concentrations of bvPLA2 (10(-12) mg ml(-1)) had some trypanocidal
      activity. Bee venom PLA2 was bactericidal to 2h bacterial cultures but
      bacteriostatic to 12h ones. Minimum bactericidal concentrations were 10(-5)-10(
      6) mg ml(-1). The results showed that bvPLA2 had significant trypanocidal and
      antibacterial effects on Gram-negative bacteria. The relationship to events
      occurring during infection is discussed. Phospholipases may play a role in
      increased endotoxin levels in trypanosomiasis.

PMID- 18343373
TI  - Regulation of vascular endothelial growth factor-A and its soluble receptor sFlt
      1 by luteinizing hormone in vivo: implication for ovarian follicle angiogenesis.
AB  - OBJECTIVE: To determine in vivo whether LH supplementation during the late
      follicular phase induces ovarian follicle angiogenesis in humans, as reflected by
      vascular endothelial growth factor (VEGF)-A, its soluble receptor sFlt-1, and
      placental growth factor (PlGF) expression. DESIGN: Randomized, double-blind,
      placebo-controlled study. SETTING: Academic tertiary care medical center.
      PATIENT(S): Twenty infertile, healthy women (aged 18-39 years) undergoing IVF.
      INTERVENTION(S): Administration of recombinant FSH after down-regulation and
      equal randomization of subjects to receive recombinant LH 75 IU/day or placebo
      when two or more follicles reached a mean diameter of 14 mm. MAIN OUTCOME
      MEASURE(S): Serum and follicular fluid (FF) VEGF-A, sFlt-1, and PlGF protein
      levels were measured. RESULT(S): Recombinant LH increased both the FF VEGF-A/sFlt
      1 ratio statistically significantly and PlGF/sFlt-1 insignificantly. Recombinant
      LH did not affect the serum VEGF/sFlt-1 ratio. Plasma levels of PlGF were
      undetectable. CONCLUSIONS: This in vivo study demonstrates for the first time in
      humans that LH induces ovarian follicular angiogenesis via modulation of VEGF-A
      and its soluble receptor sFlt-1 expression. A constant VEGF-A/sFlt-serum ratio
      may prevent adverse effects of VEGF-A. Because angiogenesis is essential during
      the periovulatory period, recombinant LH supplementation during the late
      follicular phase may improve ovulation induction outcome.

PMID- 18343374
TI  - Central retinal vein occlusion associated with clomiphene-induced ovulation.
AB  - OBJECTIVE: To report a case of central retinal vein occlusion associated with
      clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an
      academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility
      clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC
      therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation
      induction with CC. RESULT(S): A 36-year-old Chinese woman developed central
      retinal vein occlusion after eight courses of CC. A search of the literature on
      the thromboembolic complications of CC does not include this severe ophthalmic
      complication, although mild visual disturbance after CC intake is not uncommon.
      CONCLUSION(S): This is the first reported case of central retinal vein occlusion
      after treatment with CC. Extra caution is warranted in treating infertility
      patients with CC, and patients should be well informed of this side effect before
      commencement of therapy.

PMID- 18343375
TI  - Predictors of pregnancy and discontinuation of infertility services among women
      who received medical help to become pregnant, National Survey of Family Growth,
      2002.
AB  - OBJECTIVE: To determine demographic characteristics associated with pregnancy
      and, separately, discontinuation of infertility services when unsuccessful at
      achieving pregnancy, among a national sample of women who received infertility
      services. DESIGN: Using a log-linear regression model, we examined associations
      with becoming pregnant among women who had received infertility services; and
      using a Cox proportional hazards model, we examined associations with earlier
      infertility service discontinuation. SETTING: 2002 National Survey of Family
      Growth, Cycle 6. PARTICIPANT(S): A total of 530 women aged 18-44 years in the
      2002 National Survey of Family Growth who had received infertility services.
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Relative risks for predictors of
      pregnancy after receiving infertility services; median time to discontinuation of
      infertility services; hazard ratios for predictors of earlier discontinuation of
      services. RESULT(S): Fifty-nine percent of respondents became pregnant while
      receiving infertility services, and 32% reported discontinuing infertility
      services before establishing a pregnancy. Women received infertility services for
      a median of 8 months; among those who discontinued services, more than half did
      so within 1 month. Among women who received infertility services, those who were
      white, nonsmokers, nulliparous, had insurance coverage, and received more than
      advice had a higher likelihood of pregnancy. Non-whites, parous women, and
      smokers discontinued infertility services earlier than others. CONCLUSION(S):
      Patients should be adequately counseled regarding modifiable behaviors and the
      range of services available before making decisions regarding their infertility.

PMID- 18343376
TI  - Ruptured ectopic pregnancy with contralateral adnexal torsion after spontaneous
      conception.
AB  - OBJECTIVE: To describe a case of ruptured ectopic pregnancy and contralateral
      adnexal torsion after spontaneous conception. DESIGN: Case report. SETTING:
      Tertiary university medical center. PATIENT(S): A 23-year-old multiparous female
      with severe bilateral pelvic pain and a positive pregnancy test. INTERVENTION(S):
      Operative laparoscopy with detorsion of left adnexa, drainage of left ovarian
      hemorrhagic corpus luteum cyst, right salpingectomy, and dilation and curettage.
      MAIN OUTCOME MEASURE(S): Laparoscopy revealed a 5 cm hemorrhagic corpus luteum
      cyst of the left ovary, torsion of the left ovary and fallopian tube, and a
      ruptured right ampullary ectopic pregnancy. RESULT(S): Normal perfusion of left
      ovary and fallopian tube after detorsion, resolution of left ovarian hemorrhagic
      corpus luteum cyst, patent left fallopian tube with chromopertubation, and
      successful removal of ectopic pregnancy. CONCLUSION(S): This is a unique case of
      adnexal torsion and contralateral ectopic pregnancy occurring after spontaneous
      conception.

PMID- 18343377
TI  - Fresh motile testicular sperm retrieved from nonobstructive azoospermic patients
      has the same potential to achieve fertilization and pregnancy via ICSI as sperm
      retrieved from obstructive azoospermic patients.
AB  - OBJECTIVE: To compare the fertilization and pregnancy rates using fresh
      testicular sperm between nonobstructive azoospermic (NOA) patients and
      obstructive azoospermic (OA) patients. DESIGN: We evaluated sperm quality of
      testicular sperm retrieved by microdissection testicular sperm extraction (MD
      TESE) in NOA patients and compared the fertilization rate and pregnancy rate via
      intracytoplasmic sperm injection (ICSI) between NOA and OA patients. SETTING:
      Private hospital-based infertility research laboratory. PATIENT(S): A total of 58
      couples in which the husband was diagnosed with azoospermia. INTERVENTION(S):
      Analytic examination of the outcomes and description of the NOA cases achieving
      pregnancies; oocyte retrieval and testicular sperm retrieval were performed
      simultaneously. MAIN OUTCOME MEASURE(S): Comparison of fertilization rate and
      pregnancy rate at the first ICSI attempt. RESULT(S): Testicular sperm were
      retrieved from 17 of 40 NOA patients and 18 of 18 OA patients. Motile sperm were
      successfully retrieved from 16 of the 17 NOA patients. There was no significant
      difference in fertilization rate and pregnancy rate between OA and NOA cases. Of
      the 17 NOA patients, nine pregnancies were achieved using fresh motile testicular
      sperm. CONCLUSION(S): Fresh motile testicular sperm retrieved from NOA patients
      may have the same potential to achieve fertilization and pregnancy as sperm
      retrieved from OA patients. The MD-TESE technique might contribute to the high
      retrieval rate of fresh motile testicular sperm even in NOA patients.

PMID- 18343378
TI  - Interaction of Helicobacter pylori with gastric epithelial cells is mediated by
      the p53 protein family.
AB  - BACKGROUND & AIMS: Although the p53 tumor suppressor has been extensively
      studied, many critical questions remain unanswered about the biological functions
      of p53 homologs, p73 and p63. Accumulating evidence suggests that both p73 and
      p63 play important roles in regulation of apoptosis, cell differentiation, and
      therapeutic drug sensitivity. METHODS: Gastric epithelial cells were cocultured
      with Helicobacter pylori, and the roles of p63 and p73 proteins were assessed by
      luciferase reporter, real-time polymerase chain reaction, immunoblotting, and
      cell survival assays. Short hairpin RNA and dominant-negative mutants were used
      to inhibit activity of p73 and p63 isoforms. Human and murine gastric tissues
      were analyzed by immunohistochemistry with p73 and p63 antibodies and modified
      Steiner's silver method. RESULTS: Interaction of H pylori with gastric epithelial
      cells leads to robust up-regulation of p73 protein in vitro and in vivo in human
      gastritis specimens and H pylori-infected mice. The p73 increase resulted in up
      regulation of pro-apoptotic genes, NOXA, PUMA, and FAS receptor in gastric
      epithelial cells. Down-regulation of p73 activity suppressed cell death and Fas
      receptor induced by H pylori. Bacterial virulence factors within the cag
      pathogenicity island, c-Abl tyrosine kinase, and interaction with p63 isoforms
      control the activity of p73. CONCLUSION: Our findings implicate p73 in H pylori
      induced apoptosis and more generally suggest that the p53 family may play a role
      in the epithelial cell response to H pylori infection.

PMID- 18343379
TI  - Selective role for TRPV4 ion channels in visceral sensory pathways.
AB  - BACKGROUND & AIMS: Although there are many candidates as molecular
      mechanotransducers, so far there has been no evidence for molecular
      specialization of visceral afferents. Here, we show that colonic afferents
      express a specific molecular transducer that underlies their specialized
      mechanosensory function: the transient receptor potential channel, vanilloid 4
      (TRPV4). METHODS: We found TRPV4 mRNA is highly enriched in colonic sensory
      neurons compared with other visceral and somatic sensory neurons. TRPV4 protein
      was found in colonic nerve fibers from patients with inflammatory bowel disease,
      and it colocalized in a subset of fibers with the sensory neuropeptide CGRP in
      mice. We characterized the responses of 8 subtypes of vagal, splanchnic, and
      pelvic mechanoreceptors. RESULTS: Mechanosensory responses of colonic serosal and
      mesenteric afferents were enhanced by a TRPV4 agonist and dramatically reduced by
      targeted deletion of TRPV4 or by a TRP antagonist. Other subtypes of vagal and
      pelvic afferents, by contrast, were unaffected by these interventions. The
      behavioral responses to noxious colonic distention were also substantially
      reduced in mice lacking TRPV4. CONCLUSIONS: These data indicate that TRPV4
      contributes to mechanically evoked visceral pain, with relevance to human
      disease. In view of its distribution in favor of specific populations of visceral
      afferents, we propose that TRPV4 may present a selective novel target for the
      reduction of visceral pain, which is an important opportunity in the absence of
      current treatments.

PMID- 18343380
TI  - Mechanism of mitochondrial glutathione-dependent hepatocellular susceptibility to
      TNF despite NF-kappaB activation.
AB  - BACKGROUND & AIMS: Nuclear factor kappaB (NF-kappaB) is the master regulator of
      tumor necrosis factor (TNF) susceptibility. Although mitochondrial glutathione
      (mGSH) depletion was shown to sensitize hepatocytes to TNF despite NF-kappaB
      activation, the mechanisms involved, particularly the role of Bax oligomerization
      and mitochondrial outer membrane (MOM) permeabilization, 2 critical steps in cell
      death, remained unexplored. METHODS: TNF signaling at the premitochondrial and
      mitochondrial levels was analyzed in primary mouse hepatocytes with or without
      mGSH depletion. RESULTS: Unexpectedly, we observed that TNF activates caspase-8
      independently of NF-kappaB inactivation, causing Bid cleavage and mitochondrial
      Bax oligomerization. However, their predicted consequences on MOM
      permeabilization, cytochrome c release, caspase-3 activation, and hepatocellular
      death occurred only on mGSH depletion. These events were preceded by stimulated
      mitochondrial reactive oxygen species that predominantly oxidized cardiolipin,
      changes not observed in acidic sphingomyelinase (ASMase)(-/-) hepatocytes.
      Oxidized cardiolipin potentiated oligomerized Bax-induced MOM-like liposome
      permeabilization by restructuring the lipid bilayer, without effect on membrane
      Bax insertion or oligomerization. ASMase(-/-) mice with mGSH depletion by
      cholesterol loading were resistant to TNF-induced liver injury in vivo.
      CONCLUSIONS: Thus, MOM-localized oligomeric Bax is not sufficient for TNF-induced
      MOM permeabilization and cell death requiring mGSH-controlled ASMase-mediated
      mitochondrial membrane remodeling by oxidized cardiolipin generation.

PMID- 18343382
TI  - The older patient's experience of encountering professional carers and close
      relatives during an acute confusional state: an interview study.
AB  - BACKGROUND: Acute confusional state (ACS) is a common and difficult condition
      among older patients with a variety of opinions about how to act when
      encountering patients with ACS. Few studies to our knowledge have been found
      exploring the encounter from the perspective of older patients and their
      experiences. OBJECTIVES: The aim of this study was to understand the experiences
      of older patients with ACS when encountering professional carers and close
      relatives. DESIGN: In order to understand older patients' experiences of
      encounters during their ACS a latent qualitative content analysis was used.
      SETTINGS: The data collection took place at two geriatric wards in an emergency
      hospital in a metropolitan area. PARTICIPANTS: The inclusion criteria included
      being aged 65 years or older and having suffered from ACS, according to the DSM
      IV criteria, and having regained lucidity. Participants were being cared for at
      one of two geriatric wards. Patients diagnosed with dementia were excluded. About
      150 patients were screened, 67 patients fulfilled the inclusion criteria and
      seven patients were included in the study, four females and three males, aged
      between 78 and 98 years. METHODS: Data were collected by interviews. RESULTS:
      Three themes were found, namely; 'Feeling lonely within the perceived reality of
      ACS', with three sub-themes: the unequal encounter, keeping a distance and being
      an outsider; 'striving towards understanding' with two sub-themes: searching for
      answers and it takes time to understand; and 'feelings of participation in the
      encounter' with two sub-themes: a mutual understanding and feeling safe and
      supported. CONCLUSIONS: Within the encounter the older patients with ACS are
      searching for answers to what is happening and why. The patients feel dependent
      on the persons they encounter and their willingness to understand and
      communicate. The patients also feel lonely, unnecessarily questioned and
      untrustworthy; but they can also feel safe, trusted and understood.

PMID- 18343381
TI  - Adolescents and androgens, receptors and rewards.
AB  - Adolescence is associated with increases in pleasure-seeking behaviors, which, in
      turn, are shaped by the pubertal activation of the hypothalamo-pituitary-gonadal
      axis. In animal models of naturally rewarding behaviors, such as sex, testicular
      androgens contribute to the development and expression of the behavior in males.
      To effect behavioral maturation, the brain undergoes significant remodeling
      during adolescence, and many of the changes are likewise sensitive to androgens,
      presumably acting through androgen receptors (AR). Given the delicate interaction
      of gonadal hormones and brain development, it is no surprise that disruption of
      hormone levels during this sensitive period significantly alters adolescent and
      adult behaviors. In male hamsters, exposure to testosterone during adolescence is
      required for normal expression of adult sexual behavior. Males deprived of
      androgens during puberty display sustained deficits in mating. Conversely,
      androgens alone are not sufficient to induce mating in prepubertal males, even
      though brain AR are present before puberty. In this context, wide-spread use of
      anabolic-androgenic steroids (AAS) during adolescence is a significant concern.
      AAS abuse has the potential to alter both the timing and the levels of androgens
      in adolescent males. In hamsters, adolescent AAS exposure increases aggression,
      and causes lasting changes in neurotransmitter systems. In addition, AAS are
      themselves reinforcing, as demonstrated by self-administration of testosterone
      and other AAS. However, recent evidence suggests that the reinforcing effects of
      androgens may not require classical AR. Therefore, further examination of
      interactions between androgens and rewarding behaviors in the adolescent brain is
      required for a better understanding of AAS abuse.

PMID- 18343383
TI  - Gilbert syndrome, UGT1A1*28 allele, and cardiovascular disease risk: possible
      protective effects and therapeutic applications of bilirubin.
AB  - Serum bilirubin has been shown to be inversely related to cardiovascular disease
      (CVD) in both retrospective and prospective studies. Meta-analysis of existing
      studies has also confirmed that serum bilirubin concentrations are inversely
      related to CVD. Less information is known about the protective effects of
      slightly elevated serum bilirubin concentrations. In this review, we will focus
      primarily on the association of serum bilirubin and CVD and the possible
      protective roles of bilirubin, heme oxygenase (HO), and bilirubin UDP
      glucuronosyltransferase (UGT1A1). HO and biliverdin reductase control the
      formation of bilirubin, whereas UGT1A1 controls bilirubin conjugation and
      clearance. Because of the health and therapeutic implications of slightly
      elevated serum bilirubin concentrations, we will discuss the recent prospective
      studies on cardiovascular risk in individuals with Gilbert syndrome (GS) as well
      as those with the UGT1A1*28 allele. Such individuals have decreased hepatic
      bilirubin UDP-glucuronosyltransferase activity, decreased bilirubin clearance,
      and increased serum bilirubin concentrations. Lastly, we will discuss some of the
      therapeutic approaches that could be used to increase serum bilirubin
      concentrations to prevent CVD and other oxidative and inflammatory diseases.

PMID- 18343384
TI  - Dietary intake of n-3 polyunsaturated fatty acids is inversely associated with
      CRP levels, especially among male smokers.
AB  - OBJECTIVE: To examine whether dietary intake of n-3 polyunsaturated fatty acid (n
      3PUFA) is associated with serum C-reactive protein (CRP) levels with regard to
      smoking status in the Japanese general population in a cross-sectional study.
      METHODS AND RESULTS: A total of 14,191 participants aged 40-69 years were
      enrolled and divided into quartile groups according to their intake of n-3PUFA.
      Multivariate-adjusted logarithm-transformed CRP levels were compared between the
      quartile groups with regard to smoking status after adjusting for traditional
      risk factors and intake of saturated fatty acids. Adjusted CRP levels were
      inversely associated with dietary intake of n-3PUFA for both the male subjects
      and female subjects (p<0.05 for trend). A linear trend was not seen between
      intake of n-3PUFA and adjusted CRP levels in male nonsmokers. Adjusted CRP level
      in the lowest quartile group of n-3PUFA was significantly higher than the levels
      in other groups in male smokers. CONCLUSION: Sufficient dietary intake of n-3PUFA
      may attenuate inflammatory reaction and this effect is more evident among high
      risk populations such as male smokers although the small numbers of female ex
      smokers and nonsmokers limited statistical power to draw strong conclusions about
      these groups.

PMID- 18343385
TI  - Simultaneous determination of three diarylheptanoids and an alpha-tetralone
      derivative in the green walnut husks (Juglans regia L.) by high-performance
      liquid chromatography with photodiode array detector.
AB  - By optimizing extraction, separation and analytical conditions, a reliable and
      accurate high-performance liquid chromatographic (HPLC) method coupled with
      photodiode array detector (DAD) at room temperature is developed for simultaneous
      determination of three diarylheptanoids (juglanin A, juglanin B, rhoiptelol) and
      an alpha-tetralone derivative (regiolone) in methanol extracts from the green
      walnut husks (Juglans regia L.) The sample pretreatment process involved the
      reflux extraction using methanol as the extract with a ratio of liquor to sample
      of 15 mL/g. The separation was achieved on a SinoChrom ODS-AP C(18) column with
      gradient elution using acetonitrile and 2% (v/v) acetic acid in water. The intra
      day and inter-day precision (RSD%) for the analytes ranged from 1.08 to 1.51 and
      0.60 to 1.13, respectively. The average recoveries obtained were from 88.4% to
      96.2% for the analytes with RSDs below 3.13%. The correlation coefficients of the
      calibration curve exceeded 0.999. The detection limits were 0.51, 0.25, 0.32 and
      0.35 ng at a signal-to-noise ratio of 3, respectively. Quantitative analyses of
      the samples from different grown sites and in obtained different months showed
      that the contents of the analytes varied significantly. The method was then
      successfully applied for the detection and isolation of a new diarylheptanoid
      derivative in the green walnut husks (J. regia L.). The structure of the new
      compound was elucidated by various spectroscopic methods including 2D NMR
      techniques (COSY, HMQC, HMBC), HR-ESI-MS and X-ray single-crystal diffraction
      analysis.

PMID- 18343386
TI  - Pressurized liquid extraction of vitamin E from Brazilian grape seed oil.
AB  - The goal of this paper is to optimize the pressurized liquid extraction (PLE) of
      vitamin E from grape seed oil from residues of the wine industry. For this
      purpose an experimental planning to optimize the extraction of Brazilian grape
      seed oil by means of PLE with hexane as solvent was applied and the results are
      compared with conventional methods (Soxhlet and mechanical press extraction).
      Vitamin E was separated and analyzed using HPLC with UV detection. This study
      demonstrates the ability of the PLE in extracting grape seed oil rich in vitamin
      E.

PMID- 18343387
TI  - Hollow waveguide quantum cascade laser spectrometer as an online microliter
      sensor for gas chromatography.
AB  - An optical absorption sensor for gas chromatography (GC) is presented. It
      consists of a quantum cascade laser along with a long piece of Hollow Waveguide
      for Infrared (HWIR) transmission inserted into the GC line. It measures the
      infrared absorption in each individual gas peak after separation by the GC
      column, and maintains the shapes of gas peaks after the HWIR sensor, making the
      gas samples further available for other sensors. By adding an inline combustion
      module before the HWIR sensor, the concentrations of many carbon containing
      compounds can be acquired by measuring CO2 absorption in their peaks. The HWIR
      sensor detects isotopologues of CO2 separately, and therefore can be used to
      measure carbon isotope ratios of heavy compounds. Application of the HWIR sensor
      to the detection of 13CO2 and CDH3 is described.

PMID- 18343388
TI  - Capillary electrophoresis of aminoglycosides with argon-ion laser-induced
      fluorescence detection.
AB  - A new analytical method for aminoglycosides (kanamycin, bekanamycin, paromomycin
      and tobramycin) based on capillary electrophoretic separation and argon-ion laser
      induced fluorescence detection has been developed. 6-Carboxyfluorescein
      succinimidyl ester (CFSE) was used for precolumn derivatization of the non
      fluorescent aminoglycosides. Optimal separation and detection were obtained with
      an electrophoretic buffer of 30 mM sodium borate (pH 9.0) and an air-cooled argon
      ion laser (excitation at 488 nm, emission at 520 nm). The concentration limits of
      detection in aqueous solution were 3.9-8.2 nM. Combined with a simple cleanup
      procedure, this method can be applied to the determination of aminoglycosides in
      human plasma. A calibration curve ranging from 0.15 to 30 microM was shown to be
      linear. The limits of detection of aminoglycosides in human plasma were between
      14.4 and 24.0 nM. Recoveries of spiked aminoglycosides in human plasma were
      between 92 and 105%.

PMID- 18343389
TI  - Determination of 23 pesticide residues in leafy vegetables using gas
      chromatography-ion trap mass spectrometry and analyte protectants.
AB  - A gas chromatographic method was developed for simultaneously determining
      residues of 12 insecticides (acrinathrin, bifenthrin, carbofuran, cyfluthrin,
      lambda-cyhalothrin, cypermethrin, chlorfenvinphos, deltamethrin, esfenvalerate,
      fenamiphos, methiocarb and tau-fluvalinate) and 11 fungicides (cyprodinil,
      fludioxonil, iprodione, metalaxyl, penconazole, pyrimethanil, procymidone
      tebuconazole, triadimefon, triadimenol and vinclozolin) in leafy vegetables.
      Samples were extracted with acetonitrile and cleaned-up with graphitized carbon
      black/primary secondary amine (GCB/PSA) solid-phase extraction (SPE) cartridges
      using acetonitrile:toluene (3:1, v/v) as eluent. The eluate was finally
      evaporated and redissolved with 0.5 mL of acetone containing the internal
      standards (pentachlorobenzene and fenpropathrin) and three analyte protectants (3
      ethoxy-1,2-propanediol, d-sorbitol and l-gulonic acid gamma-lactone). The
      addition of analyte protectants allows to avoid the matrix-induced response
      enhancement effect on quantitation process with absolute recoveries ca. 100%.
      Precision (expressed as relative standard deviation) was lower than 10% for all
      pesticides and finally, limits of detection were also 10-20 times lower than
      maxima residue levels (MRLs) established by European Regulation. The proposed
      method was applied to determine pesticide residues in commercial leafy vegetables
      (lettuce, Swiss chard and spinach) purchased from markets in Orense (NW Spain).
      Pesticide residues were detected in 84% of the total samples (63 from 75 samples)
      and pesticide concentrations were higher than MRL in 18 samples.

PMID- 18343390
TI  - Stability-indicating hydrophilic interaction liquid chromatography method for
      highly polar and basic compounds.
AB  - A hydrophilic interaction liquid chromatography (HILIC) method was developed for
      the analysis of very polar and basic 4-(aminomethyl)pyridine (4-AMP) and its
      related compounds. Separation parameters such as stationary phase, buffer pH,
      buffer ionic strength, organic modifier, and column temperature were evaluated.
      The retention mechanisms were explored through the evaluation of the common
      chromatographic parameters in the method development. The data indicated the
      existence of surface adsorption phenomena for 4-AMP and its positional isomers (2
      AMP, 3-AMP). For two degradants, different retention mechanisms might be involved
      when compared to 4-AMP. The selectivity of two critical pairs 3-/4-AMP isomer and
      Degradant-1/-2 diastereomer changed through isoelution temperature with reversal
      of elution order. The validation results indicated that the HILIC method is a
      sensitive, reproducible, and robust method suitable for the analysis of 4-AMP and
      its related compounds.

PMID- 18343391
TI  - Method development for identification of ketobemidone metabolites in
      microdialysate samples by coupled-column capillary liquid chromatography-tandem
      mass spectrometry.
AB  - Methodologies for identification of ketobemidone metabolites in microdialysate
      samples utilizing coupled-column capillary liquid chromatography-electrospray
      quadrupole time-of-flight tandem mass spectrometry are presented. Two different
      methods were developed to efficiently analyze the metabolites norketobemidone,
      ketobemidone N-oxide and hydroxyketobemidone, respectively. Both methods include
      on-line desalting and trapping of the analytes on micro-solid-phase extraction
      columns with different retention mechanisms. Norketobemidone and ketobemidone N
      oxide were trapped on a C18 column and then eluted by back-flush followed by
      isocratic separation on a fluorinated reversed-phase type silica gel column
      (Fluofix). Retention equations are proposed for the chromatographic observations
      made on the Fluofix column. Hydroxyketobemidone was trapped on a phenylboronic
      acid column by complex formation at basic pH and then eluted at acidic pH
      directly into to the mass spectrometer. Oxidation of hydroxyketobemidone to its
      corresponding quinone was also observed. The methods were successfully used to
      analyze synthetic ketobemidone metabolites in dilute low-volume microdialysis
      samples.

PMID- 18343392
TI  - Development and optimization of a method for analyzing biodiesel mixtures with
      non-aqueous reversed phase liquid chromatography.
AB  - Biodiesel (a mixture of fatty acid esters) is normally analyzed using gas
      chromatography/flame ionization detection, as specified by the ASTM D6584 and
      EN14105 standards. This paper proposes a binary gradient method for analyzing
      biodiesel mixtures using non-aqueous reverse phase HPLC with a UV detector
      capable of overcoming the drawbacks of the gas chromatographic technique normally
      used. The new analytical method was developed by means of a statistical
      sensitivity analysis applied to the main parameters influencing the recording,
      using the full factorial design method combined with the Yates algorithm and the
      steepest ascent optimization procedure. The present study shows the influence of
      the main biodiesel mixture separation analysis parameters. The resulting tool
      proved valid for analyzing not only biodiesel but also any traces of unreacted
      oil.

PMID- 18343393
TI  - Microwave hydrodiffusion and gravity, a new technique for extraction of essential
      oils.
AB  - A new process design and operation for the extraction of essential oils was
      developed. Microwave hydrodiffusion and gravity (MHG) is a combination of
      microwaves for hydrodiffusion of essential oils from the inside to the exterior
      of biological material and earth gravity to collect and separate. MHG is
      performed at atmospheric pressure without adding any solvent or water. MHG has
      been compared with a conventional technique, hydrodistillation (HD), for the
      extraction of essential oil from two aromatic herbs: spearmint (Mentha spicata
      L.) and pennyroyal (Mentha pulegium L.) belonging to the Labiatae family. The
      essential oils extracted by MHG for 15 min were quantitatively (yield) and
      qualitatively (aromatic profile) similar to those obtained by conventional
      hydrodistillation for 90 min. MHG also prevents pollution through potential 90%
      of energy saved which can lead to greenhouse gas emission benefits.

PMID- 18343394
TI  - Spontaneous volume transition of polyampholyte nanocomposite hydrogels based on
      pure electrostatic interaction.
AB  - A circular system is employed in this paper to investigate the swelling behaviors
      of polyampholyte hydrogels; this circular system can effectively eliminate the
      disturbance of various factors and keep the surrounding environment constant. It
      is found that there exists a spontaneous volume transition to the collapsed state
      of polyampholyte hydrogels, which is attributed to the overshooting effect, and
      the transition can occur repeatedly under certain conditions. (13)C NMR is
      employed to investigate the swelling behavior of polyampholyte hydrogels. The
      swelling kinetics of polyampholyte hydrogels under various circular media and
      various circular runs are also investigated in this paper. All the results
      suggest that the spontaneous volume transition to the collapsed state of
      polyampholyte hydrogels is dominated by pure electrostatic interaction between
      different charges in polymer chains.

PMID- 18343395
TI  - The influence of ionic strength, nutrients and pH on bacterial adhesion to
      metals.
AB  - Bacteria-metal interactions in aqueous solutions are important in biofilm
      formation, biofouling and biocorrosion problems in the natural environment and
      engineered systems. In this study, the adhesion forces of two anaerobes
      (Desulfovibrio desulfuricans and Desulfovibrio singaporenus) and an aerobe
      (Pseudomonas sp.) to stainless steel 316 in various aqueous systems were
      quantified using atomic force microscopy (AFM) with a cell probe. Results show
      that the nutrient and ionic strength of the solutions influence the bacteria
      metal interactions. The bacteria-metal adhesion force was reduced in the presence
      of the nutrients in the solution, because a trace organic film was formed and
      thus decreased the metal surface wettability. Stronger ionic strength in the
      solution results in a larger bacteria-metal adhesion force, which is due to the
      stronger electrostatic attraction force between the positively charged metal
      surface and negatively charged bacterial surface. Solution pH also influences the
      interaction between the bacterial cells and the metal surface; the bacteria-metal
      adhesion force reached its highest value when the pH of the solution was near the
      isoelectric point of the bacteria, i.e. at the zero point charge. The adhesion
      forces at pH 9 were higher than at pH 7 due to the increase in the attraction
      between Fe ions and negative carboxylate groups.

PMID- 18343396
TI  - Phonological patterns in the conversational speech of children with cochlear
      implants.
AB  - In this descriptive, longitudinal study, phonological patterns (i.e., natural
      phonological processes) were examined in a set of conversational speech samples
      obtained from six young children fitted with cochlear implants. Both
      developmental and non-developmental patterns were observed. This is consistent
      with findings from previous studies of the speech of children with hearing loss
      who wear hearing aids. Several of the patterns found were also the same as those
      reported in previous studies of children with cochlear implants. One
      developmental pattern and two non-developmental patterns were significantly
      correlated with age demonstrating a decrease over time. Trends were evident in
      several other patterns suggesting possible directions for future investigations.
      LEARNING OUTCOMES: The reader will be able to (1) differentiate developmental
      from non-developmental phonological patterns, (2) identify the patterns that can
      be seen in the speech of children fitted with cochlear implants, and (3)
      understand the direction of pattern occurrence over time in this population.

PMID- 18343397
TI  - Tonsillar lymphangiomatous polyp in an adult dog.
AB  - A female spayed cocker spaniel dog, aged 8 years, developed a large, smooth
      pedunculated mass arising from the right palatine tonsil. Histology revealed that
      the mass was composed of many, variably dilated, thin-walled lymphatic channels
      filled with pale eosinophilic fluid lacking red blood cells and embedded in a
      dense, fibrovascular stroma. The dilated lymphatic channels were lined by a
      single layer of flattened, discontinuous endothelium with scattered intraluminal
      valves. Periodic acid-Schiff staining highlighted the discontinuous basement
      membrane and immunohistochemistry revealed strong cell membrane and cytoplasmic
      immunoreactivity for CD31 and von Willebrand factor, respectively. The clinical
      and histological findings were consistent with a tonsillar lymphangiomatous polyp
      - an uncommon, benign tumour of the tonsil in man that has previously been
      unrecognized in veterinary medicine.

PMID- 18343398
TI  - Pathological changes in masked palm civets experimentally infected by severe
      acute respiratory syndrome (SARS) coronavirus.
AB  - Masked palm civets are highly susceptible to infection with the severe acute
      respiratory syndrome coronavirus (SARS-CoV). Infected animals become less
      aggressive and develop pyrexia, lethargy and diarrhoea. The present study
      describes the spectrum of histopathological changes in the lung, spleen, lymph
      node, liver, small intestine, kidney and cerebrum of civets infected
      experimentally with SARS-CoV. In-situ hybridization (ISH) with probes specific
      for the RNA polymerase gene demonstrated viral RNA in the lung, small intestine
      and cerebrum only. In-situ labelling was employed in order to demonstrate
      cellular apoptosis in the cerebrum, but there was no evidence of apoptosis within
      the myocardium. These results indicate that SARS-CoV causes multi-organ pathology
      in civets, similar to that observed in human SARS patients. These parallels
      suggest that civets may be used as an animal model of this infection to gain
      insight into the pathogenesis of SARS and for evaluation of candidate vaccines
      and antiviral drugs.

PMID- 18343399
TI  - Schooling in western culture promotes context-free processing.
AB  - Culture has been shown to influence the way people apprehend their physical
      environment. Cognitive orientation is more holistic in East Asian cultures, which
      emphasize relationships and connectedness among objects in the field, than in
      Western cultures, which are more prone to focus exclusively on the object and its
      attributes. We investigated whether, beyond, or in conjunction with culture,
      literacy and/or schooling may also have an influence on this cognitive
      orientation. Using the Framed-Line Test both in Portugal and in Thailand, we
      compared literate schooled adults with two groups of unschooled adults: one of
      illiterates and one of ex-illiterates. As in former studies on Western people,
      Portuguese-schooled literates were more accurate in the absolute task than in the
      relative task. In contrast, Portuguese illiterates and ex-illiterates were more
      accurate in the relative task than in the absolute task. Such an effect of
      schooling was not observed in the Thai groups, all of whom performed better on
      the relative task. Thus, the capacity to abstract from contextual information
      does not stem only from passive exposure to the culture or the physical
      environment of Western countries. Western schooling, as part of or in addition to
      culture, is a crucial factor.

PMID- 18343400
TI  - Immunological methods to quantify and characterize proteasome complexes:
      development and application.
AB  - The ubiquitin-proteasome pathway plays major roles in all aspects of biology and
      contributes to various disease processes. Due to the lack of assays that permit
      proteasome quantification in crude cell extracts, its concentrations in health
      and disease states as well as the relationship between free 20S core particles
      (20S) and 26S proteasomes (26S) that consist of 20S singly or doubly capped with
      19S regulator complexes (19S) are still largely unknown. Thus, we established a
      20S ELISA for the detection of total 20S, and developed a specific 26S ELISA. The
      latter utilizes the ATP/Mg2+ requirement for 26S stability and shows no cross
      reactivity with 20S. Both ELISAs demonstrate intra- and inter-assay variations
      between 4.9% and 9.4% and recoveries of 105%-109%. Initial application showed
      that maintenance of the physiological ATP concentration is essential for accurate
      26S assessment. Measurements in erythrocyte and peripheral blood mononuclear cell
      (PBMNC) extracts revealed that the concentrations of 20S were 15-fold and of 26S
      130-fold higher in PBMNCs, and suggested that the 26S is the physiological
      relevant form in PBMNCs (molar ratio 20S/26S 1.1+/-0.4), whereas free 20S is
      predominant in erythrocytes (molar ratio 20S/26S: 11.5+/-4.0). During storage of
      packed red blood cell units spontaneous 26S assembly was detectable while
      specific 26S enzyme activities decreased, indicating that these assays are useful
      to assess the dynamic interplay between the 20S and 19S. During 26S assay
      development we further observed that solid phase affinity immobilization (SPAI)
      of 26S enables quantification of its dissociation into 20S and 19S. Utilizing the
      SPAI-26S method in combination with the non-hydrolyzable analogue ATP[beta,gamma
      NH] and Mg2+ depletion, we provided evidence that ATP binding without hydrolysis
      via a high affinity binding site (Kd 4-6 microM) as well as ATP binding with
      hydrolysis via a low affinity binding site that is virtually not saturable under
      physiological conditions is required to fully stabilize the 26S. Application of
      these immunological techniques is expected to facilitate proteasome analyses, and
      may help to better understand its roles in health and disease processes.

PMID- 18343401
TI  - Transmission of Pandora neoaphidis in the presence of co-occurring arthropods.
AB  - Transmission of the entomopathogenic fungus Pandora neoaphidis to the nettle
      aphid Microlophium carnosum was assessed in the presence of arthropods that co
      exist with the fungus within the habitat but do not compete for aphid hosts. The
      presence of a parasitoid significantly enhanced transmission, and transmission
      rates were similar for both enemy and non-enemy parasitoids. Although herbivory
      of nettle leaves by Peacock butterfly (Inchis io) caterpillars indirectly reduced
      the number of M. carnosum by >30% due to a reduction in leaf area for feeding,
      the addition of I. io significantly increased transmission of P. neoaphidis in
      the remaining aphids. It is likely that enhanced transmission in the presence of
      A. rhopalosiphii and I. io is due to disturbance and subsequent movement of the
      aphid, resulting in contact with conidia deposited on the leaf surface. The
      presence and impact of co-occurring arthropods should be taken into consideration
      when assessing the transmission of fungal entomopathogens.

PMID- 18343402
TI  - Detection and quantitation of Solenopsis invicta virus-2 genomic and intermediary
      replicating viral RNA in fire ant workers and larvae.
AB  - Quantitative real-time PCR (QPCR) was used to quantify the genome of Solenopsis
      invicta virus-2 (SINV-2) from infected individual ants of S. invicta. Strand
      specific cDNA synthesis oligonucleotide primers and RNase digestion after cDNA
      synthesis allowed quantification of plus (genomic) and minus (replicative)
      strands of the SINV-2 genome. Both strands were detected in adult workers and
      larval fire ants indicating that the virus was replicating within the ant. The
      differences between the genomic to replicative strand ranged from 199-fold in
      larvae to 479-fold in workers with an average ratio of 339:1.

PMID- 18343403
TI  - Allogenic mesenchymal stem cell transplantation has a therapeutic effect in acute
      myocardial infarction in rats.
AB  - The goal of the study was to examine if allogenic mesenchymal stem cell (MSC)
      transplantation is a useful therapy for acute myocardial infarction (AMI). Buffer
      (control; group C, n=41), MSCs of male ACI rats (allogenic; group A, n=38, 5 x
      10(6)), or MSCs of male LEW rats (syngenic; group S, n=40, 5 x 10(6)) were
      injected into the scar 15 min after myocardial infarction in female LEW rats.
      After 28 days, fractional left ventricular shortening significantly increased in
      groups A (21.3+/-1.7%, P=0.0467) and S (23.2+/-1.9%, P=0.0140), compared to group
      C (17.1+/-0.9%). Fibrosis in groups A and S was significantly lower. Quantitative
      PCR of the male-specific sry gene showed disappearance of donor cells within 28
      days (5195+/-1975 cells). Secretion of vascular endothelial growth factor (VEGF)
      by MSCs was enhanced under hypoxic conditions in vitro. In groups A and S, the
      plasma VEGF concentration, VEGF level, and capillary density in recipient hearts
      increased after 28 days. Flow cytometry revealed the absence of B7 signal
      molecules on MSCs. A mixed lymphocyte reaction showed that ACI MSCs failed to
      stimulate proliferation of LEW lymphocytes. After 1 day after cell
      transplantation, transient increases in interleukin-1 beta and monocyte
      chemoattractant protein-1 in recipient hearts were enhanced in group A, with
      macrophage infiltration at the injection site. T cells remained at the level of
      normal tissue in all groups. We conclude that allogenic MSC transplantation
      therapy is useful for AMI. The donor MSCs disappear rapidly, but become a trigger
      of VEGF paracrine effect, without induction of immune rejection.

PMID- 18343404
TI  - Three-dimensional architecture of membrane-embedded MscS in the closed
      conformation.
AB  - The mechanosensitive channel of small conductance (MscS) is part of a coordinated
      response to osmotic challenges in Escherichia coli. MscS opens as a result of
      membrane tension changes, thereby releasing small solutes and effectively acting
      as an osmotic safety valve. Both the functional state depicted by its crystal
      structure and its gating mechanism remain unclear. Here, we combine site-directed
      spin labeling, electron paramagnetic resonance spectroscopy, and molecular
      dynamics simulations with novel energy restraints based on experimental electron
      paramagnetic resonance data to investigate the native transmembrane (TM) and
      periplasmic molecular architecture of closed MscS in a lipid bilayer. In the
      closed conformation, MscS shows a more compact TM domain than in the crystal
      structure, characterized by a realignment of the TM segments towards the normal
      of the membrane. The previously unresolved NH(2)-terminus forms a short helical
      hairpin capping the extracellular ends of TM1 and TM2 and is in close interaction
      with the bilayer interface. The present three-dimensional model of membrane
      embedded MscS in the closed state represents a key step in determining the
      molecular mechanism of MscS gating.

PMID- 18343405
TI  - Coupling and dynamics of subunits in the hexameric AAA+ chaperone ClpB.
AB  - The bacterial AAA+ protein ClpB and its eukaryotic homologue Hsp104 ensure
      thermotolerance of their respective organisms by reactivating aggregated proteins
      in cooperation with the Hsp70/Hsp40 chaperone system. Like many members of the
      AAA+ superfamily, the ClpB protomers form ringlike homohexameric complexes. The
      mechanical energy necessary to disentangle protein aggregates is provided by ATP
      hydrolysis at the two nucleotide-binding domains of each monomer. Previous
      studies on ClpB and Hsp104 show a complex interplay of domains and subunits
      resulting in homotypic and heterotypic cooperativity. Using mutations in the
      Walker A and Walker B nucleotide-binding motifs in combination with mixing
      experiments we investigated the degree of inter-subunit coupling with respect to
      different aspects of the ClpB working cycle. We find that subunits are tightly
      coupled with regard to ATPase and chaperone activity, but no coupling can be
      observed for ADP binding. Comparison of the data with statistical calculations
      suggests that for double Walker mutants, approximately two in six subunits are
      sufficient to abolish chaperone and ATPase activity completely. In further
      experiments, we determined the dynamics of subunit reshuffling. Our results show
      that ClpB forms a very dynamic complex, reshuffling subunits on a timescale
      comparable to steady-state ATP hydrolysis. We propose that this could be a
      protection mechanism to prevent very stable aggregates from becoming suicide
      inhibitors for ClpB.

PMID- 18343406
TI  - Crystal structure and standardized geometric analysis of InlJ, a listerial
      virulence factor and leucine-rich repeat protein with a novel cysteine ladder.
AB  - We report on the crystal structure of the internalin domain of InlJ, a virulence
      associated surface protein of Listeria monocytogenes, at 2.7-A resolution. InlJ
      is a member of the internalin family of listerial cell surface proteins
      characterized by a common N-terminal domain. InlJ bears 15 leucine-rich repeats
      (LRRs), the same number as in InlA, the prototypical internalin family member.
      The LRRs of InlJ differ from those of other internalins by having 21, rather than
      22, residues and by replacing 1 LRR-defining hydrophobic residue with a conserved
      cysteine. These cysteines stack to form an intramolecular ladder and regular
      hydrophobic interactions in consecutive repeats. Analyzing the curvature, twist,
      and lateral bending angles of InlJ and comparing these with several other LRR
      proteins, we provide a systematic geometric comparison of LRR protein structures
      (http://bragi2.helmholtz-hzi.de/Angulator/). These indicate that both cysteine
      and asparagine ladders stabilize the LRR fold, whereas substitutions in some
      repeat positions are more likely than others to induce changes in LRR geometry.

PMID- 18343407
TI  - alpha B-crystallin is a cytoplasmic interaction partner of the kidney-specific
      cadherin-16.
AB  - The Ca(2+)-dependent membrane-spanning classical cadherins bind directly to
      cytosolic catenins. This cadherin-catenin interaction is known to be critical for
      the fundamental role of cadherins in cell-cell adhesion. The small subfamily of
      the 7D-cadherins, however, cannot interact with catenins due to their highly
      truncated cytoplasmic tail. Thus far, no cytoplasmic interaction partner for the
      7D-cadherins has been described. With the use of the cytoplasmic domain of the
      Ksp (kidney-specific)-cadherin, which belongs to the family of 7D-cadherins, as
      bait in affinity chromatography with human kidney lysates, the small heat-shock
      protein alpha B-crystallin was identified by matrix-assisted laser
      desorption/ionization-time-of-flight analysis as a cytosolic binding partner of
      Ksp-cadherin. This interaction was verified by co-immunoprecipitation analysis.
      With the use of overlapping peptides representing the entire alpha B-crystallin
      molecule, the N-terminal part of alpha B-crystallin, which does not possess
      chaperone activity, was identified as responsible for the binding to Ksp
      cadherin. This interaction was found to be specific since only the cytoplasmic
      domain of Ksp-cadherin, but not LI (liver-intestine)-cadherin (another member of
      the 7D-cadherin family), interacted with alpha B-crystallin. In the human kidney,
      both alpha B-crystallin and Ksp-cadherin co-localize to cells of the collecting
      duct. They also co-localize with the actin cytoskeleton and co-precipitate with
      the latter. These findings suggest that the interaction of Ksp-cadherin with
      alpha B-crystallin is important for the connection of Ksp-cadherin to the
      cytoskeleton and thus for maintaining tissue integrity in the kidney.

PMID- 18343408
TI  - Gadd45 beta forms a homodimeric complex that binds tightly to MKK7.
AB  - Gadd45 alpha, beta, and gamma proteins, also known as growth arrest and DNA
      damage-inducible factors, have a number of cellular functions, including cell
      cycle regulation and propagation of signals produced by a variety of cellular
      stimuli, maintaining genomic stability and apoptosis. Furthermore, Gadd45 beta
      has been indicated as a major player in the endogenous NF-kappaB-mediated
      resistance to apoptosis in a variety of cell lines. In fibroblasts this mechanism
      involves the inactivation of MKK7, the upstream activator of JNK, by direct
      binding within the kinase ATP pocket. On the basis of a number of experimental
      data, the structures of Gadd45 beta and the Gadd45 beta-MKK7 complex have been
      predicted recently and data show that interactions are mediated by acidic loops 1
      and 2, and helices 3 and 4 of Gadd45 beta. Here, we provide further evidence that
      Gadd45 beta is a prevailingly alpha-helical protein and that in solution it is
      able to form non covalent dimers but not higher-order oligomers, in contrast to
      what has been reported for the homologous Gadd45 alpha. We show that the contact
      region between the two monomers is comprised of the predicted helix 1 (residues
      Q17-Q33) and helix 5 (residues K131-R146) of the protein, which appear to be
      antiparallel and to form a large dimerisation surface not involved in MKK7
      recognition. The results suggest the occurrence of a large complex containing at
      least an MKK7-Gadd45 beta:Gadd45 beta-MKK7 tetrameric unit whose complexity could
      be further increased by the dimeric nature of the isolated MKK7.

PMID- 18343409
TI  - Patterns of vegetation biodiversity: the roles of dispersal directionality and
      river network structure.
AB  - This paper investigates the importance of dispersal directionality and river
      network structure to biodiversity patterns. Our model results suggest that
      dispersal directionality plays a crucial role in determining biodiversity
      patterns, even more so than dispersal rates. Dispersal directionality
      heterogenizes the spatial distribution of abundance, which results in higher
      extinction rates of rare species and higher beta diversity. It induces a few
      species with very high abundances at the expense of many species with
      intermediate abundances, thereby lowering alpha and gamma diversities. The river
      network structure also increases beta diversity, i.e., more heterogeneous
      ecosystems, in comparison to typical two-dimensional landscapes. We find that the
      interplay between the dispersal directionality and network topology has important
      consequences on relative species abundance patterns and the distribution of alpha
      diversity.

PMID- 18343410
TI  - Dynamics of sialyl Lewis(a) in aqueous solution and prediction of the structure
      of the sialyl Lewis(a)-SelectinE complex.
AB  - In this article we investigate all possible three-dimensional structures for
      sialyl Lewis(a) (SLe(a)) in aqueous solution and we predict without a priori
      experimental information its conformation when bound to SelectinE by using a
      combination of long molecular dynamics (MD) simulations. Based on 10ns MD
      studies, three structures differing in glycosidic conformations are proposed for
      SLe(a) in aqueous solution. Based on a 4ns MD study of the SLe(a)-SelectinE
      complex with initial structures derived from our prediction tools, we find that,
      fucose and N-acetyl neuraminic acid are in close contact with SelectinE and
      therefore expect interactions of the protein with these two sugar rings to be
      significantly more important than in the case of galactose and N-acetyl
      glucosamine. Our predictions indicate that the N-acetyl glucosamine of SLe(a) is
      positioned primarily in the aqueous phase. In order to be able to interact with
      SLe(a) the side chains of amino acid residues Lys99 and Lys111 in SelectinE
      appear to undergo large conformational changes when contrasted with the positions
      of these residues in the X-ray crystal structure. Furthermore, amino acid
      residues Arg97, Glu98 and Lys99 are acting as a holding arm to position the
      NeuNAc of SLe(a) in the binding pocket.

PMID- 18343411
TI  - Patch exploitation in two dimensions: from Daphnia to simulated foragers.
AB  - We explore the variability that animals display in their movement choices as they
      forage in a finite-sized food patch with a uniform food distribution, and present
      a framework for how these choices may be adjusted to optimize foraging
      efficiency. Inspired by experimental studies of the zooplankton Daphnia, we model
      foraging animals as "agents" moving in two dimensions in repeated and successive
      sequences of hops, pauses, and turns. For Daphnia and other species, critical
      movement parameters such as hop lengths, pause times, and turning angles are
      typically reported as probability density functions. Similarly, the agents in our
      simulations choose their movement parameters at random from such distributions.
      Each distribution is defined by a characteristic width, which we interpret as a
      "noise width," available to be tuned for increased foraging efficiency. We
      investigate the sensitivity of the system by measuring the food gathered by the
      agents as the turning angle and hop length noise widths are varied. In all cases,
      we find a maximum in food gathered at some particular value of the noise width in
      question, suggesting that these results can be considered robust examples of
      natural stochastic resonance.

PMID- 18343412
TI  - Saturation technique does not decrease cancer detection during followup after
      initial prostate biopsy.
AB  - PURPOSE: It has been reported that the prostate cancer detection rate in men with
      prostate specific antigen 2.5 ng/ml or greater undergoing saturation (20 cores or
      greater) prostate biopsy as an initial strategy is not higher than that in men
      who undergo 10 to 12 core prostate biopsy. At a median followup of 3.2 years we
      report the cancer detection rate on subsequent prostate biopsy in men who
      underwent initial saturation prostate biopsy. MATERIALS AND METHODS: Saturation
      prostate biopsy was used as an initial biopsy strategy in 257 men between January
      2002 and April 2006. Cancer was initially detected in 43% of the patients who
      underwent saturation prostate biopsy. In the 147 men with negative initial
      saturation prostate biopsy followup including digital rectal examination and
      repeat prostate specific antigen measurement was recommended at least annually.
      Persistently increased prostate specific antigen or an increase in prostate
      specific antigen was seen as an indication for repeat saturation prostate biopsy.
      RESULTS: During the median followup of 3.2 years after negative initial
      saturation prostate biopsy 121 men (82%) underwent subsequent evaluation with
      prostate specific antigen and digital rectal examination. Median prostate
      specific antigen remained 4.0 ng/ml or greater in 57% of the men and it increased
      by 1 ng/ml or greater in 23%. Cancer was detected in 14 of 59 men (24%)
      undergoing repeat prostate biopsy for persistent clinical suspicion of prostate
      cancer. No significant association was demonstrated between cancer detection and
      initial or followup prostate specific antigen, or findings of atypia and high
      grade prostatic intraepithelial neoplasia on initial saturation prostate biopsy.
      Cancers detected on repeat prostate biopsy were more likely to be Gleason 6 and
      organ confined at prostatectomy than were those diagnosed on initial saturation
      prostate biopsy. CONCLUSIONS: Previous experience suggests that, while office
      based saturation prostate biopsy improves cancer detection in men who have
      previously undergone a negative prostate biopsy, it does not improve cancer
      detection as an initial biopsy technique. We now report that the false-negative
      rate on subsequent prostate biopsy after initial saturation prostate biopsy is
      equivalent to that following traditional prostate biopsy. These data provide
      further evidence against saturation prostate biopsy as an initial strategy.

PMID- 18343414
TI  - Evaluation of prostatitis in autopsied prostates--is chronic inflammation more
      associated with benign prostatic hyperplasia or cancer?
AB  - PURPOSE: Chronic inflammation is associated with prostate cancer and benign
      prostatic hyperplasia. However, the prevalence of chronic inflammation in
      malignant and benign glands has not been compared. We evaluated the association
      of inflammation, benign prostatic hyperplasia and cancer in autopsied prostates.
      MATERIALS AND METHODS: We prospectively analyzed 167 autopsied prostates.
      Pathological analysis identified each focus of cancer, benign prostatic
      hyperplasia nodules and areas of acute or chronic inflammation. Any cancer focus
      or benign prostatic hyperplasia nodule involved directly with inflammation was
      recorded. The association of the prevalence of prostate cancer, benign prostatic
      hyperplasia and inflammation was statistically assessed. RESULTS: Inflammation
      was present in 113 (67.6%) of 167 cases. Chronic inflammation was identified in
      88 (53%), acute inflammation in 6 (4%), and chronic inflammation and acute
      inflammation in 19 (11%) glands. In the majority of cases inflammation was
      present in the transitional zone. A total of 93 glands (56%) were involved with
      benign prostatic hyperplasia and 49 (29%) with cancer. Of the glands harboring
      benign prostatic hyperplasia 75% were also involved with chronic inflammation
      compared to only 50% of those without benign prostatic hyperplasia (p <0.01).
      Comparatively the glands with or without any evidence of cancer were similarly
      involved with chronic inflammation (55% vs 58%, p >0.1). Of the 27 glands
      involved with cancer and benign prostatic hyperplasia, chronic inflammation was
      more associated with benign prostatic hyperplasia than cancer (p = 0.006). Acute
      inflammation was not significantly associated with either benign prostatic
      hyperplasia or cancer. CONCLUSIONS: Chronic inflammation was a common finding in
      autopsied prostates. It appeared to be directly associated with the presence of
      benign prostatic hyperplasia but not with cancer.

PMID- 18343416
TI  - Female stress urinary incontinence--where are we?

PMID- 18343417
TI  - Challenging the orthodoxy in vesicoureteral reflux: a perfect storm.

PMID- 18343419
TI  - Editorial comment.

PMID- 18343420
TI  - The ratio of serum testosterone-to-prostate specific antigen predicts prostate
      cancer in hypogonadal men.
AB  - PURPOSE: We determined whether the ratio of serum testosterone to prostate
      specific antigen might provide diagnostic value regarding the risk of prostate
      cancer in a population of hypogonadal men undergoing prostate biopsy. MATERIALS
      AND METHODS: The study population consisted of 184 consecutive men with
      symptomatic hypogonadism and prostate specific antigen 4.0 ng/ml or less who
      underwent prostate biopsy before the anticipated initiation of testosterone
      therapy. All men had testosterone 300 ng/dl or less. Testosterone concentrations
      were converted to ng/ml, eg 270 ng/dl equals 2.7 ng/ml, to calculate the
      testosterone-to-prostate specific antigen ratio. RESULTS: Mean patient age was
      58.5 years. There were 154 men with benign biopsies and 30 with cancer.
      Testosterone concentrations were similar in the prostate cancer and noncancer
      groups, although mean prostate specific antigen was higher in the prostate cancer
      group. The testosterone-to-prostate specific antigen ratio was inversely related
      to prostate cancer risk (OR 0.49, 95% CI 0.33-0.74). On multivariate analysis
      performed by logistic regression neither age nor prostate specific antigen was be
      predictive of prostate cancer. However, the testosterone-to-prostate specific
      antigen ratio remained strongly associated with prostate cancer risk. An ROC for
      the testosterone-to-prostate specific antigen ratio suggested that a ratio of
      below 1.8 was diagnostic for prostate cancer, while values below this threshold
      were associated with an OR of 3.17 (95% CI 1.17-8.59) for prostate cancer.
      CONCLUSIONS: A low ratio of testosterone to prostate specific antigen is an
      independent predictor of prostate cancer in hypogonadal men with prostate
      specific antigen 4.0 ng/ml or less. Ratios less than 1.8 were associated with a
      greater than 3-fold increase in prostate cancer risk.

PMID- 18343421
TI  - Potency preserving cystectomy with intrafascial prostatectomy for high risk
      superficial bladder cancer.
AB  - PURPOSE: We report the oncological and functional results of potency sparing
      cystectomy with intrafascial prostatectomy for high risk, superficial bladder
      cancer. MATERIALS AND METHODS: A total of 37 patients underwent potency sparing
      cystectomy and orthotopic urinary substitution from 2001 to 2005. Inclusion
      criteria were age younger than 70 years, Charlson comorbidity index less than 2,
      high risk superficial bladder cancer, prostate specific antigen less than 4
      ng/ml, free-to-total PSA ratio greater than 20% and normal digital rectal
      examination. RESULTS: Median patient age was 58 years (range 52 to 66). Median
      followup was 35 months (range 24 to 71). One patient died of disease progression
      and 1 died of an unrelated cause. Of the 37 patients 35 (95%) were free of tumor.
      Daily continence was achieved in 36 patients (97.2%) and nighttime continence was
      achieved in 35 (95%). Two patients (5%) needed clean intermittent
      catheterization. A total of 35 patients (95%) stated that they maintained
      erectile function, including 28 (76%) without oral drugs. A significant decrease
      in the median International Index of Erectile Function score from baseline was
      noted 2 years after surgery (25 vs 21). A total of 32 patients (86%) had an
      International Index of Erectile Function score of greater than 17 at 2 years
      after cystectomy. Median scores on the International Continence Society male
      short form questionnaires did not show any significant difference before and
      after surgery. Prostate specific antigen was lower than 0.2 ng/ml in all cases.
      CONCLUSIONS: The main criticism about so-called sexuality sparing cystectomy has
      been the presence of consistent prostatic remnants. Performing intrafascial
      prostatectomy together with supra-ampullar cystectomy seems to warrant good
      functional results with while better preserving oncological safety.

PMID- 18343422
TI  - William E. Bradley and his contributions to urology.
AB  - PURPOSE: We review the myriad contributions to urological science by neurologist
      and engineer, William E. Bradley. MATERIALS AND METHODS: Remembrances and
      personal interviews were collated for this article. RESULTS: Doctor Bradley was a
      pioneer in neurourology. He described a neurophysiological paradigm for
      micturition, devised urodynamic and electrophysiological techniques, and
      contributed to the development of genitourinary prosthetic devices. CONCLUSIONS:
      Doctor Bradley made notable and groundbreaking contributions to urology, many of
      which are still in use today.

PMID- 18343423
TI  - A road map to biomarker discovery and validation in urological chronic pelvic
      pain syndrome.

PMID- 18343424
TI  - Predicting prostate cancer behavior--what is a urologist to do?

PMID- 18343425
TI  - The performance of prostate specific antigen, prostate specific antigen density
      and transition zone density in the era of extended biopsy schemes.
AB  - PURPOSE: Prostate specific antigen, prostate specific antigen density and
      transition zone density have been previously identified as prostate cancer
      detection tools. Recent studies suggest that prostate specific antigen may be
      increasingly accurate for detecting clinically significant high grade prostate
      cancer (Gleason grade 7 or greater). We defined the performance of these measures
      in a referral based population undergoing an extended prostate biopsy scheme.
      MATERIALS AND METHODS: We retrospectively reviewed prospectively collected data
      on 1,708 men referred for prostate needle biopsy. All participants were men who
      had not undergone biopsy in the past. From these data ROC curves were constructed
      for prostate specific antigen, prostate specific antigen density and transition
      zone density for the presence of cancer, high grade (Gleason 3 + 4 or greater)
      and high volume (50% or greater of cores positive) disease. RESULTS: Prostate
      specific antigen density had a statistically higher AUC than prostate specific
      antigen for detecting all prostate cancers (0.737 vs 0.633, p <0.001) as well as
      high grade (0.766 vs 0.673, p <0.001) and high volume (0.843 vs 0.755, p <0.001)
      disease. Additionally, prostate specific antigen and prostate specific antigen
      density performed better for detecting high grade and high volume disease
      compared to overall prostate cancer detection. The performance of transition zone
      density was similar to that of prostate specific antigen density. CONCLUSIONS:
      Prostate specific antigen and prostate specific antigen density show improved
      performance characteristics for detecting clinically significant high grade and
      high volume prostate cancer in referral populations undergoing extended scheme
      prostate needle biopsy. Prostate specific antigen density shows better
      performance characteristics than prostate specific antigen. No advantage was seen
      when using transition zone density over prostate specific antigen density.

PMID- 18343426
TI  - Risk stratification for biochemical recurrence in men with positive surgical
      margins or extracapsular disease after radical prostatectomy: results from the
      SEARCH database.
AB  - PURPOSE: In men with extracapsular disease or positive surgical margins after
      radical prostatectomy immediate adjuvant therapy decreases the risk of
      biochemical recurrence at the cost of increased toxicity. We further stratified
      these men into a low risk group in which watchful waiting after surgery may be
      preferred and a high risk cohort in which adjuvant therapy may be preferred.
      MATERIALS AND METHODS: We performed a retrospective analysis of the records of
      902 men treated with radical prostatectomy in the Shared Equal-Access Regional
      Cancer Hospital (SEARCH) database between 1988 and 2007 with positive surgical
      margins and/or extracapsular disease without seminal vesicle invasion or lymph
      node metastasis. The significant independent predictors of biochemical recurrence
      were determined using a multivariate Cox proportional hazards model. Based on the
      recurrence risk generated from the multivariate Cox proportional hazards
      regression model we generated tables to estimate the risk of recurrence-free
      survival 1, 3 and 5 years after surgery. RESULTS: At a median of 3 years of
      followup 346 patients (39%) had biochemical recurrence. On multivariate analysis
      the significant predictors of biochemical recurrence were age more than 60 years,
      prostate specific antigen more than 10 ng/ml, Gleason score 4 + 3 and 8-10, 2 or
      more sites of positive surgical margins and prostate specimen weight 30 gm or
      less. As determined by the concordance index, the overall predictive accuracy of
      the model was 0.67, while it was 0.60 for the postoperative Kattan nomogram in
      this patient population. CONCLUSIONS: We have developed a simple instrument that,
      once validated, may aid in the postoperative decision making process for men at
      intermediate risk for recurrence after prostatectomy.

PMID- 18343427
TI  - Prognostic significance of alpha-methylacyl-coA racemase among men with high
      grade prostatic intraepithelial neoplasia in prostate biopsies.
AB  - PURPOSE: Serum prostate specific antigen screening has increased the number of
      prostate biopsies performed increasing the number of patients with high grade
      prostatic intraepithelial neoplasia. The criteria for re-biopsy are not
      standardized but may be refined by the identification of novel biomarkers
      demonstrating prognostic significance. Alpha-methylacyl-CoA racemase is a robust
      marker of prostate cancer and is expressed in a subset of high grade prostatic
      intraepithelial neoplasia. This study evaluates the prognostic significance of
      alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial
      neoplasia glands in prostate biopsies. MATERIALS AND METHODS: Immunohistochemical
      staining with alpha-methylacyl-coA racemase and p63 was examined in a selected
      group of 62 patients with a diagnosis of high grade prostatic intraepithelial
      neoplasia on initial prostate biopsy, of which on repeat biopsy 32 had no
      carcinoma and 30 had prostate cancer. There was no significant difference in age,
      number of cores sampled or prostate specific antigen history between the 2
      outcome groups (ANOVA p >0.9). High grade prostatic intraepithelial neoplasia
      glands in each case were evaluated for alpha-methylacyl-coA racemase and p63.
      RESULTS: Reactivity for alpha-methylacyl-coA racemase was found in 27 of the 62
      cases examined. Fisher's exact analysis revealed that patients with at least 1
      alpha-methylacyl-coA racemase positive high grade prostatic intraepithelial
      neoplasia gland were 5.2 times more likely to have a subsequent diagnosis of
      prostate cancer on repeat biopsy than those without any alpha-methylacyl-coA
      racemase positive high grade prostatic intraepithelial neoplasia glands (p =
      0.0044). No correlation was found between alpha-methylacyl-coA racemase
      positivity and any other clinical variable. CONCLUSIONS: This is the first study
      to our knowledge to illustrate that alpha-methylacyl-coA racemase reactivity in
      high grade prostatic intraepithelial neoplasia may be useful to refine re-biopsy
      criteria and assist in clinical management decisions.

PMID- 18343428
TI  - Does obesity impact the costs of partial and radical nephrectomy?
AB  - PURPOSE: We analyzed the impact of obesity on the costs of partial and radical
      nephrectomy. MATERIALS AND METHODS: The charts of 237 patients who underwent open
      radical nephrectomy (48), laparoscopic radical nephrectomy (67), open partial
      nephrectomy (61) or laparoscopic partial nephrectomy (61) were retrospectively
      reviewed. Clinical data were collected, including age, American Society of
      Anesthesiologists score, body mass index, tumor size, complications and length of
      stay. Cost data comprised total direct costs and subcosts, including anesthesia,
      laboratory, operating room service, radiology, room and board, pharmacy and
      surgical supplies. Obese and nonobese patients were compared in each group using
      the Mann-Whitney U and chi-square tests for continuous and categorical variables,
      respectively. Univariate analysis was used to assess predictors of direct costs.
      RESULTS: Length of stay was longer in obese patients in the open partial
      nephrectomy group (p = 0.04). There were no differences between obese and
      nonobese patients in terms of complications and comorbidities. Costs were higher
      in obese patients in the open partial nephrectomy group ($10,187 vs $6,538, p =
      0.02). There were no other differences in cost between obese and nonobese
      patients in the 3 other surgical groups. On univariate analysis length of stay
      robustly predicted the cost of each kind of operation (p <0.0001). Obesity status
      was almost a significant predictor of direct cost in the open partial nephrectomy
      group (p = 0.056). CONCLUSIONS: Body mass index had an impact on costs only in
      the subset of patients who underwent open partial nephrectomy. Length of stay
      seems to be the main determinant of costs in renal surgery. Further studies are
      warranted.

PMID- 18343430
TI  - Sex differences in renal cell cancer presentation and survival: an analysis of
      the National Cancer Database, 1993-2004.
AB  - PURPOSE: We analyzed patterns of disease presentation and outcome of renal cell
      carcinomas by gender using data from the National Cancer Database during a 10
      year period. We hypothesized that women presented with lower stage disease and
      had increased survival than men due to increased imaging. MATERIALS AND METHODS:
      The National Cancer Database is a nationwide oncology data set that currently
      captures approximately 75% of all newly diagnosed cancer cases from more than
      1,400 facility based cancer registries in the United States annually since 1985.
      The National Cancer Database was queried for adults with renal cell carcinoma
      diagnosed between 1993 and 2004. Cases were examined according to gender in
      relation to mean age, American Joint Committee on Cancer stage, histology, grade,
      tumor size, mortality and race. RESULTS: We identified a total of 236,930
      patients with renal cell carcinoma diagnosed between 1993 and 2004 from the
      National Cancer Database. A total of 89,243 (37.7%) were female and 147,687
      (62.3%) were male. Mean age was greater in females (64.3) than in males (62.9) (p
      <0.001). Women had a higher percentage of stage I tumors (54.1% vs 48.5%, p
      <0.001). Progressive stage migration was documented in men and women. A trend
      toward increased survival was noted in women relative to men that did not reach
      statistical significance. CONCLUSIONS: Results from this study show a ratio of
      1.65 of renal cell carcinoma for males compared to females. Women are more likely
      than men to have stage I tumors. Both men and women have demonstrated stage
      migration, although women more so than men.

PMID- 18343432
TI  - Tertiary Gleason pattern 5 in Gleason 7 prostate cancer predicts pathological
      stage and biochemical recurrence.
AB  - PURPOSE: Gleason sum 7 prostate cancers are a heterogeneous group with diverse
      tumor behaviors and disease outcomes. Tertiary Gleason patterns are reported with
      increasing frequency, particularly in prostatectomy pathology reports. We studied
      the pathological and biochemical outcome following radical prostatectomy in men
      with Gleason sum 7 and tertiary Gleason pattern 5. MATERIALS AND METHODS: We
      reviewed 1,110 cases of clinically localized prostate cancer treated with primary
      radical prostatectomy between January 1998 and August 2006 through a
      prospectively collected prostate cancer database. Patients who underwent
      neoadjuvant or adjuvant hormonal deprivation, radiation or systemic chemotherapy
      were excluded. RESULTS: Of the 1,110 patients 509 had Gleason sum 7 cancer.
      Tertiary Gleason pattern was present in 66 of 509 cases (13%) and it was absent
      in 443 (87%). On multivariate analysis tertiary Gleason pattern 5 was associated
      with higher pT stage (OR 2.55, 95% CI 1.40-4.65) and biochemical recurrence (HR
      1.78, 95% CI 1.00-3.17). On subgroup analysis when patients with Gleason sum 3 +
      4 + 5 and 4 + 3 + 5 were compared to their respective referent groups without the
      tertiary Gleason pattern, the 2 groups showed a trend toward higher pathological
      stage and prostate specific antigen progression. Patients with Gleason sum 3 + 4
      with no tertiary pattern had higher PSA recurrence-free probability than those
      with Gleason sum 3 + 4 + 5 or 4 + 3 and patients with Gleason sum 4 + 3 + 5 had
      the lowest PSA recurrence-free probability. CONCLUSIONS: In patients with Gleason
      sum 7 prostate cancer tertiary Gleason grade 5 is significantly associated with
      higher pT stage and biochemical recurrence. Larger studies are needed to assess
      the predictive value of tertiary grade compared to other established parameters
      in predicting the long-term oncological outcome after radical prostatectomy.

PMID- 18343434
TI  - Limitations of prostate specific antigen doubling time following biochemical
      recurrence after radical prostatectomy: results from the SEARCH database.
AB  - PURPOSE: Prostate specific antigen doubling time following biochemical recurrence
      after radical prostatectomy is a powerful predictor of prostate cancer specific
      and overall death. To calculate prostate specific antigen doubling time requires
      multiple prostate specific antigen determinations that are unaltered by secondary
      therapy and separated by sufficient time. Physicians and patients may be
      unwilling to wait before starting secondary therapy, especially for high risk
      recurrences. Hence, those with calculable prostate specific antigen doubling time
      may represent a select lower risk group relative to all men with biochemical
      recurrence. MATERIALS AND METHODS: We compared clinical and pathological features
      between patients with and without calculable prostate specific antigen doubling
      time. We assessed time trends in the proportion with calculable prostate specific
      antigen doubling time in 535 patients with biochemical recurrence after radical
      prostatectomy at 5 Veterans Affairs medical centers comprising the SEARCH (Shared
      Equal Access Regional Cancer Hospital) database between 1988 and 2003. RESULTS:
      Prostate specific antigen doubling time was not calculable in 187 patients (35%)
      due to secondary therapy in 155 (83%). With time the proportion of patients with
      calculable prostate specific antigen doubling time decreased significantly (p
      <0.001). Adverse pathological features, more rapid time to recurrence, higher
      body mass index and differing surgical centers were associated with not having a
      calculable prostate specific antigen doubling time. Of all men with recurrence in
      the most recent year of analysis the adjusted probability of having a calculable
      prostate specific antigen doubling time was only 43%, that is 61% in patients
      with favorable pathological results but only 30% in those with seminal vesicle
      invasion. CONCLUSIONS: Those with calculable prostate specific antigen doubling
      time represented a select, lower risk cohort and the proportion of patients with
      calculable prostate specific antigen doubling time decreased with time. This
      highlights the need for alternative markers in men with recurrent prostate cancer
      because one of our best current markers, prostate specific antigen doubling time,
      is only available in a limited number of patients.

PMID- 18343437
TI  - Tumor size does not predict risk of metastatic disease or prognosis of small
      renal cell carcinomas.
AB  - PURPOSE: We characterized the clinicopathological features and the prognosis of
      small solid renal tumors defined as tumors 4 cm or smaller. MATERIALS AND
      METHODS: We identified 1,208 patients who were treated with nephrectomy at 5
      international academic centers for small solid renal tumors. Clinicopathological
      parameters and outcome data were collected for each patient and analyzed.
      RESULTS: Of the tumors 88% were renal cell carcinoma and 12% were benign. Of
      those with renal cell carcinoma 995 (93%) were localized (N0M0) and 72 (7%)
      presented with metastatic disease. Tumor size did not predict synchronous
      metastatic disease. The incidence of metastatic disease in the tumor size ranges
      0.1 to 1.0, 1.1 to 2.0, 2.1 to 3.0 and 3.1 to 4.0 cm was 7%, 6%, 5% and 8%,
      respectively (p = 0.322). Survival rates were excellent. The majority of patients
      who died of renal cell carcinoma (54%) presented with synchronous metastatic
      disease, but 3% of patients with localized disease also died of renal cell
      carcinoma. In patients with localized disease there was a 7% chance of recurrence
      post nephrectomy at 5 years. Progression-free survival (28 months) was better
      than for patients with metastatic disease having a primary tumor greater than 4
      cm (8 months). Tumor size was not retained as an independent prognostic factor of
      survival in multivariate analyses. The University of California Integrated
      Staging System and the Karakiewicz nomogram were the best predictors of cancer
      specific survival for all renal cell carcinoma stages (c-index 0.87).
      CONCLUSIONS: More than 85% of small solid renal tumors are renal cell carcinoma.
      The majority of localized small renal tumors can be cured with existing surgical
      approaches. However, there is a small but not insignificant risk of synchronous
      and metachronous metastatic disease and cancer associated death. Patients
      considering experimental therapies such as ablation and surveillance should be
      aware of this. Tumor size alone is not sufficient to distinguish renal cell
      carcinoma with benign behavior from aggressive small renal cell carcinoma.
      Survival of patients with small metastatic renal cell carcinoma is better then
      expected. The biology of these unique tumors should be further studied.

PMID- 18343439
TI  - Prostate specific antigen versus prostate specific antigen density as a
      prognosticator of pathological characteristics and biochemical recurrence
      following radical prostatectomy.
AB  - PURPOSE: The usefulness of prostate specific antigen density for predicting
      pathological stage and biochemical recurrence after radical prostatectomy has not
      been well defined. We investigated whether prostate specific antigen density
      yielded an advantage over total prostate specific antigen for predicting adverse
      pathological characteristics and disease recurrence following radical
      prostatectomy. MATERIALS AND METHODS: A total of 13,434 men who underwent radical
      prostatectomy for clinically localized prostate cancer between 1984 and 2006 were
      included in this study. The study population was stratified by Gleason score (6
      or less, 7, and 8 or greater), and the clinical and pathological characteristics
      of each group were compared. We constructed ROC curves and determined the ROC AUC
      and concordance index to specifically investigate the accuracy of prostate
      specific antigen and prostate specific antigen density for predicting
      pathological stage and biochemical recurrence. RESULTS: Prostate specific antigen
      density was better than prostate specific antigen for predicting extraprostatic
      extension and biochemical-free recurrence in patients with a biopsy Gleason score
      of 6 or less (each p <0.001). In patients with a biopsy Gleason score of 7
      prostate specific antigen was more predictive than prostate specific antigen
      density for seminal vesicle involvement (p <0.001), lymph node involvement (p =
      0.017) and biochemical-free recurrence (p <0.001). In men with a biopsy Gleason
      score of 8 or greater there was no statistical difference between prostate
      specific antigen and prostate specific antigen density in terms of prognostic
      value for pathological or clinical outcomes. CONCLUSIONS: Prostate specific
      antigen density is highly associated with pathological stage and biochemical-free
      survival following radical prostatectomy. In lower grade prostate cancers
      prostate specific antigen density is significantly more accurate for predicting
      extraprostatic extension and biochemical-free recurrence compared to total
      prostate specific antigen. It should be considered when counseling patients on
      outcomes following radical prostatectomy.

PMID- 18343440
TI  - Patterns of primary and secondary therapy for prostate cancer in elderly men:
      analysis of data from CaPSURE.
AB  - PURPOSE: We examined patterns of primary treatment for prostate cancer in men 75
      years or older. MATERIALS AND METHODS: Data were obtained from the multi
      institutional CaPSURE database on the type of primary therapy performed in men
      younger than 75, or 75 years old or older. Primary therapy was defined as
      watchful waiting, radical prostatectomy, brachytherapy, brachytherapy plus
      external beam radiotherapy, external beam radiotherapy or primary androgen
      deprivation therapy. The chi-square test and multinomial logistic regression
      analysis were performed to identify predictors of the type of primary therapy and
      outcomes. RESULTS: A greater proportion of patients 75 years or older were white,
      single, had multiple comorbidities, low income and low education, and were
      classified as being at high risk compared to those younger than 75 years (43% vs
      25%). On multivariate analysis adjusted for sociodemographic factors, diagnostic
      risk category and the number of comorbidities at diagnosis patients 75 years or
      older were less likely to be treated with primary therapy than with watchful
      waiting regardless of the risk category or comorbidity level. CONCLUSIONS: Older
      patients with high risk cancer are far more likely to be observed regardless of
      the burden of comorbidity. A more tailored approach to prostate cancer therapy
      that considers comorbidity and functional level to determine primary therapy may
      be more appropriate. Well selected older patients with high risk disease,
      particularly those with low comorbidity levels, may derive survival benefit from
      a primary therapy other than watchful waiting. Alternatively elderly patients
      with low risk disease may be better treated with watchful waiting.

PMID- 18343441
TI  - Surgical simulation: a urological perspective.
AB  - PURPOSE: Surgical education is changing rapidly as several factors including
      budget constraints and medicolegal concerns limit opportunities for urological
      trainees. New methods of skills training such as low fidelity bench trainers and
      virtual reality simulators offer new avenues for surgical education. In addition,
      surgical simulation has the potential to allow practicing surgeons to develop new
      skills and maintain those they already possess. We provide a review of the
      background, current status and future directions of surgical simulators as they
      pertain to urology. MATERIALS AND METHODS: We performed a literature review and
      an overview of surgical simulation in urology. RESULTS: Surgical simulators are
      in various stages of development and validation. Several simulators have
      undergone extensive validation studies and are in use in surgical curricula.
      While virtual reality simulators offer the potential to more closely mimic
      reality and present entire operations, low fidelity simulators remain useful in
      skills training, particularly for novices and junior trainees. Surgical
      simulation remains in its infancy. However, the potential to shorten learning
      curves for difficult techniques and practice surgery without risk to patients
      continues to drive the development of increasingly more advanced and realistic
      models. CONCLUSIONS: Surgical simulation is an exciting area of surgical
      education. The future is bright as advancements in computing and graphical
      capabilities offer new innovations in simulator technology. Simulators must
      continue to undergo rigorous validation studies to ensure that time spent by
      trainees on bench trainers and virtual reality simulators will translate into
      improved surgical skills in the operating room.

PMID- 18343442
TI  - The arachidonic acid pathway and its role in prostate cancer development and
      progression.
AB  - PURPOSE: The arachidonic acid pathway incorporates phospholipase, cyclooxygenase,
      lipoxygenase and epoxygenase enzymes. This pathway has been shown to have a major
      role in the development and progression of a number of cancers, including
      prostate cancer. We discuss the current status of research of this pathway in the
      area of prostate cancer, ranging from preclinical in vitro studies to human
      clinical trials. MATERIALS AND METHODS: We performed an online search of the
      current and past peer reviewed literature on prostate cancer and arachidonic
      acid, phospholipase, cyclooxygenase, lipoxygenase, epoxygenase, platelet
      activating factor, prostaglandin and eicosanoid. We retrieved and evaluated all
      full-length articles published in English from the 1980s to January 2007.
      RESULTS: Epidemiological evidence suggested that nonsteroidal anti-inflammatory
      drugs may decrease the risk of prostate cancer. This effect, presumably through
      the inhibition of cyclooxygenase-2, has been validated in preclinical studies.
      Cyclooxygenase-2 inhibition has also decreased the rate of prostate specific
      antigen increase in men with biochemical recurrence after treatment for prostate
      cancer. Although lipoxygenase and secretory phospholipase A2 inhibition was also
      effective for decreasing prostate cancer growth in preclinical studies, to our
      knowledge these strategies have not yet been used in clinical trials. Cytosolic
      phospholipase A2, platelet activating factor and epoxygenase need further
      investigation to determine a role in prostate cancer. CONCLUSIONS: Evolving data
      suggest a significant role for some areas of the arachidonic acid pathway in
      prostate cancer. Inhibiting 1 or a number of these enzymes in combination may
      hold promise for future prostate cancer treatment.

PMID- 18343443
TI  - Racial/ethnic and gender disparities in renal cell carcinoma incidence and
      survival.
AB  - PURPOSE: We used a population based cancer registry to examine trends in renal
      cell carcinoma incidence and survival among 4 racial/ethnic groups (white, black,
      Hispanic and Asian/Pacific Islander) and both genders. MATERIALS AND METHODS:
      Race/ethnicity, gender, age, staging, length of survival and cause of death data
      were analyzed using 39,434 cases of renal cell carcinoma from 1988 to 2004 from
      the California Cancer Registry. Annual age adjusted incidence rates and relative
      survival rates were calculated for the racial/ethnic and gender groups. These
      rates and the percent of localized cancer were plotted by year, and Microsoft
      Excel was used to calculate linear regression equations. Median age was also
      calculated. Z-tests and chi-square tests were performed to determine p values.
      RESULTS: An increase in renal cell carcinoma incidence was found with localized
      cancer accounting for most of the increase. Black patients had a significantly
      higher incidence rate (p <0.0001) and lower survival rate (p <0.0001) than all
      other races/ethnicities despite having more localized cancer (p <0.005). Black
      patients were also diagnosed at a younger age (p <0.0001) than their
      counterparts. On the other hand Asian/Pacific Islanders had a lower incidence
      rate (p <0.0001) and higher survival rate (p <0.05) than all other
      races/ethnicities. Males had approximately twice the incidence rate of females
      and a lower survival rate (p <0.005). CONCLUSIONS: Higher incidence rates and
      lower survival rates were identified among black and male patients compared to
      their counterparts, while Asian/Pacific Islanders showed the opposite trends.
      Such racial/ethnic and gender disparities in renal cell carcinoma incidence and
      survival may help elucidate biological, behavioral and environmental factors that
      can potentially be addressed.

PMID- 18343445
TI  - Single photon emission computerized tomography with capromab pendetide plus
      computerized tomography image set co-registration independently predicts
      biochemical failure.
AB  - PURPOSE: We evaluate the usefulness of pretreatment (111)Indium capromab
      pendetide (ProstaScint) planar imaging (immunoscintigraphy) plus single photon
      emission tomography co-registration with computerized tomography scans to detect
      occult metastatic disease and predict for biochemical failure, in a cohort of
      patients with a clinical diagnosis of localized adenocarcinoma of the prostate
      referred for primary radiotherapy. MATERIALS AND METHODS: Patients were followed
      after radiotherapy for evidence of biochemical failure using 2 criteria of
      prostate specific antigen clinical nadir +2 ng/ml and American Society for
      Therapeutic Radiology and Oncology Consensus definitions. Median followup was
      58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high
      (51), intermediate (72) and low (116). RESULTS: Overall biochemical failure was
      18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median
      followup. By the CN +2 definition the control date for the cohort is 34.8 months.
      Pretreatment SPECT/CT suggested prostate cancer metastasis (22), seminal vesicle
      extension (20) and organ confined disease (197). Biochemical failure in patients
      having extra-periprostatic metastatic prostate cancer, seminal vesicle extension
      and organ confined disease uptake on SPECT/CT was 43.2%, 16.0% vs 14.7% (p =
      0.0006); and 33.3%, 15.0% vs 8.7% (p = 0.0017) by the 2-BFC, respectively. Cox
      multiple regression analysis demonstrated that a finding of extra-periprostatic
      metastatic prostate on SPECT/CT significantly predicted a 4.2-fold greater risk
      (p = 0.0012) and a 4.5-fold greater risk (p = 0.0011) of failure by the 2-BFC
      than organ confined disease adjusting for treatment and risk group. CONCLUSIONS:
      Unconfirmed findings of extra-periprostatic metastatic prostate cancer on
      SPECT/CT immunoscintigraphy independently and significantly predicted an
      increased risk of biochemical failure in patients presenting for radiotherapy
      with a clinical diagnosis of localized prostate cancer.

PMID- 18343448
TI  - The behavior of renal cell carcinoma: sex, lies and tumor size.

PMID- 18343449
TI  - The male urethral sphincter complex revisited: an anatomical concept and its
      physiological correlate.
AB  - PURPOSE: The anatomy of the male urethral sphincter has not been stable since it
      was first described more than 150 years ago. Although 18th and 19th century
      historical descriptions of the urethral sphincter are most accurate and
      comprehensive, modern textbooks lack details and include inaccuracies and
      misleading illustrations. This is an attempt to achieve a revised concept of the
      male urethral sphincter complex. MATERIALS AND METHODS: A thorough review of the
      English literature in the last 100 years, and of pertinent Germinal publications
      and textbooks of the 19th and 20th centuries was done. Also, we reviewed
      urodynamic findings in male patients in whom the urethral sphincters had been
      expectedly damaged in the proximal or distal part by surgery during the last 20
      years. RESULTS: The current concept of urethral sphincter anatomy does not differ
      much from that described and illustrated in the 19th century. The disagreement
      between the historical and recent descriptions is primarily concerned with the
      cranial extension of the skeletal muscle component and the caudal extension of
      the smooth muscle component in the urethral wall. CONCLUSIONS: The male urethral
      sphincter complex is composed of an inner lissosphincter of smooth muscle and an
      outer rhabdosphincter of skeletal muscle. It extends in the form of a cylinder
      around the urethra from the vesical orifice to the perineal membrane. While the
      rhabdosphincter is most marked around the membranous urethra and becomes
      gradually less distinct toward the bladder, the lissosphincter has its main part
      at the vesical orifice and is thinner in its further course in the urethra. The
      lissosphincter is primarily concerned with the function of continence at rest. On
      the other hand, the rhabdosphincter has a dual genitourinary function, namely
      active continence during stress conditions and antegrade semen propulsion.

PMID- 18343450
TI  - Editorial comment.

PMID- 18343451
TI  - Update on primary hypercalciuria from a genetic perspective.
AB  - PURPOSE: This review provides a brief update on genetic studies of primary
      hypercalciuria. We consider their possible implications for the pathogenesis and
      complications of primary hypercalciuria. MATERIALS AND METHODS: Using the PubMed,
      MEDLINE and Scopus databases we reviewed the literature on pathogenesis and the
      complications of hypercalciuria, giving particular attention to genetic studies
      in humans. RESULTS: Primary hypercalciuria is a defect occurring in 5% to 10% of
      the general population and it is most commonly detected in patients with calcium
      kidney stones or osteoporosis. In children it is associated with hematuria, renal
      stones or nocturnal enuresis. Although high penetrance, autosomal dominant
      inheritance cannot be ruled out, hypercalciuria is probably a polygenic disorder.
      A number of genes have been suggested as candidates in the pathogenesis of common
      idiopathic calcium nephrolithiasis and hypercalciuria, ie soluble adenylate
      cyclase, calcium sensing receptor, vitamin D receptor, chloride channel-5, sodium
      phosphate cotransporter-2 and claudin-16. These genes may also have a role in
      complications of hypercalciuria. CONCLUSIONS: The classic distinction among
      absorptive, renal and resorptive hypercalciuria seems insufficient to explain the
      many cellular and tissue modifications observed in patients with primary
      hypercalciuria. The condition seems to be a separate disorder, characterized by
      altered calcium transport in the intestine, kidney and bone, and caused by
      various combinations of multiple genetic and dietary changes.

PMID- 18343454
TI  - Central zone carcinoma of the prostate gland: a distinct tumor type with poor
      prognostic features.
AB  - PURPOSE: The central zone of the prostate gland is a region rarely associated
      with carcinoma. To our knowledge central zone tumors have not previously been
      compared to carcinoma originating in the peripheral or transition zone of the
      prostate gland. MATERIALS AND METHODS: All 2,010 radical prostatectomy cases seen
      at our institution from October 1998 to December 2006 were reviewed to identify
      tumor zonal origin. Central zone carcinoma was characterized and compared with
      tumors of other zones. RESULTS: Zonal origin was determined in a total of 2,494
      tumors in 1,703 cases. Of the tumors 63 (2.5%) were of central zone origin with
      59 of the 63 representing the index or main tumor. Comparative analysis of a
      defined subset of 726 cases showed that central zone cancers were significantly
      more aggressive than peripheral or transition zone cancers with a far greater
      risk of extracapsular extension, seminal vesicle invasion and positive surgical
      margins. Escape from the gland was often via the ejaculatory ducts and seminal
      vesicles. Kaplan-Meier analysis confirmed that the probability of post
      prostatectomy biochemical failure was double that of tumors of the other zones
      with a far more rapid rate of failure. Multivariate Cox regression analysis
      identified Gleason grade, positive margins, extracapsular extension, tumor volume
      and preoperative serum prostate specific antigen as the major contributors to
      this poor prognosis, rather than specific zonal origin. CONCLUSIONS: To our
      knowledge this study provides the first characterization and comparative analysis
      of central zone carcinoma, identifying these tumors as a rare but highly
      aggressive form of prostate carcinoma with a distinct route of spread from the
      gland that contrasts with tumors of other zones. Preoperative identification is
      currently hampered by the avoidance of biopsy targeting the central zone.
      However, if recognized preoperatively, aggressive intervention may possibly
      improve the currently bleak outlook.

PMID- 18343455
TI  - Rationale and procedures.

PMID- 18343457
TI  - Sonication of bacteria, phytoplankton and zooplankton: Application to treatment
      of ballast water.
AB  - We investigated the effect of high power ultrasound, at a frequency of 19 kHz, on
      the survival of bacteria, phytoplankton and zooplankton, in order to obtain
      estimates of effective exposure times and energy densities that could be applied
      to design of ultrasonic treatment systems for ballast water. Efficacy of
      ultrasonic treatment varied with the size of the test organism. Zooplankton
      required only 3-9s of exposure time and 6-19 J/mL of ultrasonic energy to realize
      a 90% reduction in survival. In contrast, decimal reduction times for bacteria
      and phytoplankton ranged from 1 to 22 min, and decimal reduction energy densities
      from 31 to 1240 J/mL. Our results suggest that stand-alone ultrasonic treatment
      systems for ballast water, operating at 19-20 kHz, may be effective for
      planktonic organisms >100 microm in size, but smaller planktonic organisms such
      as phytoplankton and bacteria will require treatment by an additional or
      alternative system.

PMID- 18343456
TI  - Effect of chronic stress on gastric emptying and plasma ghrelin levels in rats.
AB  - Chronic stress is associated with gastrointestinal functional diseases. Although
      the pathophysiology seems to be associated with gastrointestinal motility, their
      mechanisms remain unclear. We investigated gastric emptying and chemical
      mediators under conditions of continuous stress, which were produced using 8-week
      old male Wistar rats kept in a cage filled with water to 2 cm height for 5 days.
      We examined gastric emptying by the phenol red method and chemical mediators at
      4, 8, and 24 h and 3 and 5 days after initiation of stress restraint. Plasma ACTH
      level was significantly higher in the stress throughout the period of
      measurement. Continuous stress delayed gastric emptying until 24 h: peak delay
      was observed at 8 h, whereas gastric emptying was accelerated on days 3 and 5.
      Plasma noradrenalin level was significantly elevated at every time point until 24
      h. Guanethidine pretreatment eliminated the delay in gastric emptying at 8 h.
      Active ghrelin was significantly increased on days 3 and 5 after peak (at 24 h)
      plasma total and desacyl ghrelin in the stress group. Number of ghrelin
      immunoreactive cells and level of preproghrelin mRNA expression in the gastric
      body increased in parallel with plasma active ghrelin level. Pretreatment with
      growth hormone secretagogue receptor antagonist at 5 days partially inhibited the
      stress-induced acceleration of gastric emptying. Delayed gastric emptying at
      acute phase of continuous stress was mediated via sympathetic pathway, while
      acceleration at chronic phase was mediated via increased active ghrelin release
      from the stomach.

PMID- 18343458
TI  - Towards a classification of organic enrichment in marine sediments based on
      biogeochemical indicators.
AB  - A nomogram is developed to show that pH, redox potentials (Eh(NHE)) and measures
      of dissolved sulfides (H2S + HS(-) + S(2-))(total free S(2-)) can be used to
      classify organic enrichment impacts in marine sediments. The biogeochemical cycle
      of sulfur in marine sediments is described to show that changes in macrobenthic
      infauna community structure associated with high levels of organic matter supply
      result from stress due to oxygen deficiency (hypoxia and anoxia) and toxic
      effects of S(2-). The changes reflect enhancement of microbial sulfate reduction
      under conditions of high organic matter sedimentation and the progressive
      formation of hypoxic-anoxic conditions measured by decreased Eh NHE and increased
      concentrations of S(2-). The nomogram provides a basis for classification of the
      oxic status of marine sediments based on changes in inter-related biological and
      biogeochemical variables along an organic enrichment gradient.

PMID- 18343459
TI  - Involvement of recQ in the ultraviolet damage repair pathway in Deinococcus
      radiodurans.
AB  - Deinococcus radiodurans is a bacterium which can survive extremely DNA damage. To
      investigate the relationship between recQ and the ultraviolet radiation (UV)
      damage repair pathway, we created a four mutant strain by constructing recQ
      knockout mutants in uvrA1, uvrA2, and uvsE backgrounds. Using the rpoB/Rif(r)
      system, we measured the mutation frequencies and rates in wild type, recQ (MQ),
      uvsE uvrA1 uvrA2 (TNK006), and uvsE uvrA1 uvrA2 recQ (TQ). We then isolated
      Rif(r) mutants of these strains and sequenced the rpoB gene. The mutation
      frequency of TQ was 6.4, 10.1, and 2.43 times that of wild type, MQ, and TNK006,
      respectively, and resulted in rates of 4.7, 6.71, and 2.15 folds higher than that
      of wild type, MQ, and TNK006, respectively. All the strains demonstrated specific
      mutational hotspots. Furthermore, the TQ strain showed a transversion bias that
      was different from the other three strains. The results indicate that recQ is
      involved in the ultraviolet damage repair pathway via the interaction between
      recQ and uvrA1, uvrA2, and uvsE in D. radiodurans.

PMID- 18343460
TI  - [Cervicomanubrial route for the ventral upper thoracic spine: technical note
      about six cases].
AB  - Ventrolateral cervicotomy provides a narrowed working space for surgical
      management of upper thoracic spine. We report our experience about ventral upper
      thoracic spinal cord decompression with reconstruction and plating via the
      cervicomanubrial route. Six patients (24 to 75 years old) were operated on by the
      same operator (LN) by cervicomanubriotomy from 2002 to 2007 for upper thoracic
      spinal cord compression (one case of Pott's disease, three cases of metastases,
      one fracture, one invasive hemangio-epithelioma), with a good outcome in five
      patients. Lesions were located from the cervicothoracic junction down to the
      fourth thoracic vertebra (T4). In all cases, anterior spinal cord decompression,
      strut graft reconstruction (iliac bone in two cases, cement in four cases) and
      osteosynthesis were performed. In two cases, a second stage posterior
      decompression with fixation was performed. The approach begins by a left sided
      anterior cervicotomy, medial to the sternocleidomastoid muscle and lateral to the
      trachea and esophagus, associated with division of the infrahyoid muscles close
      to their insertion at the upper thoracic outlet followed by osteotomy of the
      manubrium sterni. Then, division of the thyropericardic fascia and thymus,
      control of the brachiocephalic vein, control of the thoracic lymphatic duct and
      the horizontal thoracic aorta are performed. The ventral part of fifth cervical
      vertebra body down to T4 is then exposed between the left primitive carotid
      artery laterally, the esophagus medially and the thoracic aorta caudally.
      Compared to total sternotomy without or with clavicle resection,
      cervicomanubriotomy seems to be a less aggressive, safe and reliable procedure.

PMID- 18343461
TI  - Inhibition of opioid release in the rat spinal cord by alpha2C adrenergic
      receptors.
AB  - Neurotransmitter receptors that control the release of opioid peptides in the
      spinal cord may play an important role in pain modulation. Norepinephrine,
      released by a descending pathway originating in the brainstem, is a powerful
      inducer of analgesia in the spinal cord. Adrenergic alpha2C receptors are present
      in opioid-containing terminals in the dorsal horn, where they could modulate
      opioid release. The goal of this study was to investigate this possibility.
      Opioid release was evoked from rat spinal cord slices by incubating them with the
      sodium channel opener veratridine in the presence of peptidase inhibitors
      (actinonin, captopril and thiorphan), and was measured in situ through the
      internalization of mu-opioid receptors in dorsal horn neurons. Veratridine
      produced internalization in 70% of these neurons. The alpha2 receptor agonists
      clonidine, guanfacine, medetomidine and UK-14304 inhibited the evoked mu-opioid
      receptor internalization with IC50s of 1.7 microM, 248 nM, 0.3 nM and 22 nM,
      respectively. However, inhibition by medetomidine was only partial, and
      inhibition by UK-14304 reversed itself at concentrations higher than 50 nM. None
      of these agonists inhibited mu-opioid receptor internalization produced by
      endomorphin-2, showing that they inhibited opioid release and not the
      internalization itself. The inhibitions produced by clonidine, guanfacine or UK
      14304 were completely reversed by the selective alpha2C antagonist JP-1203. In
      contrast, inhibition by guanfacine was not prevented by the alpha2A antagonist
      BRL-44408. These results show that alpha2C receptors inhibit the release of
      opioids in the dorsal horn. This action may serve to shut down the opioid system
      when the adrenergic system is active.

PMID- 18343462
TI  - Memory retrieval and the parietal cortex: a review of evidence from a dual
      process perspective.
AB  - Although regions of the parietal cortex have been consistently implicated in
      episodic memory retrieval, the functional roles of these regions remain poorly
      understood. The present review presents a meta-analysis of findings from event
      related fMRI studies reporting the loci of retrieval effects associated with
      familiarity- and recollection-related recognition judgments. The results of this
      analysis support previous suggestions that retrieval-related activity in lateral
      parietal cortex dissociates between superior regions, where activity likely
      reflects the task relevance of different classes of recognition test items, and
      more inferior regions where retrieval-related activity appears closely linked to
      successful recollection. It is proposed that inferior lateral parietal cortex
      forms part of a neural network supporting the 'episodic buffer' [Baddeley, A. D.
      (2000). The episodic buffer: A new component of working memory? Trends in
      Cognitive Sciences, 4, 417-423].

PMID- 18343463
TI  - Abeta deposits in older non-demented individuals with cognitive decline are
      indicative of preclinical Alzheimer's disease.
AB  - Approximately 30% of healthy persons aged over 75 years show Abeta deposition at
      autopsy. It is postulated that this represents preclinical Alzheimer's disease
      (AD). We evaluated the relationship between Abeta burden as assessed by PiB PET
      and cognitive decline in a well-characterized, non-demented, elderly cohort. PiB
      PET studies and cognitive tests were performed on 34 elderly participants (age
      73+/-6) from the longitudinal Melbourne Healthy Aging Study (MHAS). Subjects were
      classified as being cognitively 'stable' or 'declining' by an independent
      behavioural neurologist based on clinical assessment and serial word-list recall
      scores from the preceding 6-10 years. Decline was calculated from the slope of
      the word-list recall scores. Abeta burden was quantified using Standardized
      Uptake Value normalized to cerebellar cortex. Ten subjects were clinically
      classified as declining. At the time of the PET scans, three of the declining
      subjects had mild cognitive impairment, one had AD, and six were declining but
      remained within the normal range for age on cognitive tests. Declining subjects
      were much more likely to show cortical PiB binding than stable subjects (70% vs.
      17%, respectively). Neocortical Abeta burden correlated with word-list recall
      slopes (r=-0.78) and memory function (r=-0.85) in the declining group. No
      correlations were observed in the stable group. Abeta burden correlated with
      incident memory impairment and the rate of memory decline in the non-demented
      ageing population. These observations suggest that neither memory decline nor
      Abeta deposition are part of normal ageing and likely represent preclinical AD.
      Further longitudinal observations are required to confirm this hypothesis.

PMID- 18343464
TI  - New measures improve the accuracy of the directed-lie test when detecting
      deception using a mock crime.
AB  - The present study tested the accuracy of probable-lie and directed-lie polygraph
      tests. One hundred and twenty men and women were recruited from the general
      community and paid $30 to participate in a mock crime experiment. Equal numbers
      of males and females were assigned to either the guilty or innocent condition
      with equal numbers in each group receiving either a probable-lie or a directed
      lie polygraph test resulting in a 2 x 2 design with two experimental factors
      (test type and deceptive condition). Half of the participants were guilty and
      half were innocent of committing a mock theft of $20 from a purse. All
      participants were paid a $50 bonus if they could convince the polygraph examiner
      that they were innocent. There were no significant differences in decision
      accuracy between probable-lie and directed-lie tests, but respiration measures
      were more diagnostic for the probable-lie test. New physiological measures, skin
      potential excursion and a new respiratory measure improved the accuracy of the
      directed-lie test such that 86% of the innocent participants and 93% of the
      guilty participants were correctly classified.

PMID- 18343465
TI  - Chemistry and weak antimicrobial activities of phomopsins produced by mangrove
      endophytic fungus Phomopsis sp. ZSU-H76.
AB  - Three metabolites named phomopsin A (1), B (2) and C (3), together with two known
      compounds cytosporone B (4) and C (5), were isolated from the mangrove endophytic
      fungus, Phomopsis sp. ZSU-H76 obtained from the South China Sea. Their structures
      were elucidated by spectroscopic methods, mainly by 1D and 2D NMR spectroscopic
      techniques. The medium-sized cyclic phenol ether based on 1 or 2 is rare in
      natural products. In bioassays, compounds 1, 2, and 3 had no significant
      antibiotic activities, but compounds 4 and 5 inhibited two fungi Candida albicans
      and Fusarium oxysporum with an MIC ranging from 32 to 64 microg/ml.

PMID- 18343466
TI  - Cordyceps: a traditional Chinese medicine and another fungal therapeutic
      biofactory?
AB  - Traditional Chinese medicines (TCM) are growing in popularity. However, are they
      effective? Cordyceps is not studied as systematically for bioactivity as another
      TCM, Ganoderma. Cordyceps is fascinating per se, especially because of the
      pathogenic lifestyle on Lepidopteron insects. The combination of the fungus and
      dead insect has been used as a TCM for centuries. However, the natural fungus has
      been harvested to the extent that it is an endangered species. The effectiveness
      has been attributed to the Chinese philosophical concept of Yin and Yang and can
      this be compatible with scientific philosophy? A vast literature exists, some of
      which is scientific, although others are popular myth, and even hype. Cordyceps
      sinensis is the most explored species followed by Cordyceps militaris. However,
      taxonomic concepts were confused until a recent revision, with undefined material
      being used that cannot be verified. Holomorphism is relevant and contamination
      might account for some of the activity. The role of the insect has been ignored.
      Some of the analytical methodologies are poor. Data on the "old" compound
      cordycepin are still being published: ergosterol and related compounds are
      reported despite being universal to fungi. There is too much work on crude
      extracts rather than pure compounds with water and methanol solvents being over
      represented in this respect (although methanol is an effective solvent).
      Excessive speculation exists as to the curative properties. However, there are
      some excellent pharmacological data and relating to apoptosis. For example, some
      preparations are active against cancers or diabetes which should be fully
      investigated. Polysaccharides and secondary metabolites are of particular
      interest. The use of genuine anamorphic forms in bioreactors is encouraged.

PMID- 18343467
TI  - Rhamnoarabinosyl and rhamnoarabinoarabinosyl side chains as structural features
      of coffee arabinogalactans.
AB  - The hot water soluble green coffee arabinogalactans, representing nearly 7% of
      total coffee bean arabinogalactans, were characterized by (1)H and (13)C NMR and,
      after partial acid hydrolysis, by ESI-MS/MS. Data obtained showed that these are
      highly branched type II arabinogalactans covalently linked to proteins (AGP),
      with a protein moiety containing 10% of 4-hydroxyproline residues. They possess a
      beta-(1-->3)-Galp/beta-(1-->3,6)-Galp ratio of 0.80, with a sugars composition of
      Rha:Ara:Gal of 0.25:1.0:1.5, and containing 2mol% of glucuronic acid residues.
      Beyond the occurrence of single alpha-L-Araf residues and [alpha-L-Araf-(1-->5)
      alpha-L-Araf-(1-->] disaccharide residues as side chains, these AGPs contain
      unusual side chains at O-3 position of the beta-(1-->6)-linked galactopyranosyl
      residues composed by [alpha-L-Rhap-(1-->5)-alpha-L-Araf-(1-->] and [alpha-L-Rhap
      (1-->5)-alpha-L-Araf-(1-->5)-alpha-L-Araf-(1-->] oligosaccharides.
      Rhamnoarabinosyl and rhamnoarabinoarabinosyl side chains are reported for the
      first time as structural features of plant arabinogalactan-proteins.

PMID- 18343468
TI  - Evaluation of different API systems for identification of porcine Pasteurella
      multocida isolates.
AB  - An exhaustive biochemical characterisation of 60 porcine Pasteurella multocida
      clinical isolates recovered from lesions indicative of pneumonia, previously
      confirmed by PCR and all belonging to the capsular serogroup A, was performed by
      means of four commercial systems. The API 20NE correctly identified almost all
      isolates (95%), but only 60% could be ascribed to this species by the API 20E
      method. The high diversity exhibited by the API 50CHB/E system, with six
      different patterns, does not advise its use as additional system for a definitive
      identification at the species level, but this method could be a potential tool
      for characterising P. multocida isolates below this level. The more uniform
      reactions yielded by the API ZYM test make this system helpful in the
      confirmatory identification of this organism. The high variability (20 profiles)
      obtained when the four systems are taken together also suggests their usefulness
      for epidemiological purposes in order to sub-type P. multocida isolates.

PMID- 18343469
TI  - [Temporal cellulitis of odontogenic origin complicated by temporomandibular
      osteoarthritis].
AB  - INTRODUCTION: Temporal cellulitis complicated by temporomandibular osteoarthritis
      and mandibular osteomyelitis is rare with the availability of antibiotics and the
      prevention of dental infections. CASE REPORT: A 56 year-old woman developed a jaw
      abscess during hospitalization in an intensive care unit following medical drug
      overdose. Repeatedly surgical drainage was performed guided by CT scans and
      multiple antibiotherapies. CT scan follow-up revealed temporomandibular arthritis
      with decrease of the joint space, synovitis, and subchondral cysts. Slow
      improvement was noted but limited mouth opening was persistent. DISCUSSION: This
      case illustrates the insidious evolution of an uncommon infection. It requires
      both expert clinical evaluation and an early MRI or CT scan investigation to
      determine the extension of the infection. Treatment is urgent because of the
      prognosis and is achieved by surgical drainage and adequate long-term
      antibiotherapy.

PMID- 18343470
TI  - Predictable ecology and geography of avian influenza (H5N1) transmission in
      Nigeria and West Africa.
AB  - The emerging virus strain termed highly pathogenic H5N1 avian influenza (HP-H5N1)
      has spread widely in the past decade and is now the focus of considerable concern
      in several sectors. We tested the hypothesis that spatial distributions of
      veterinary and human HP-H5N1 cases are related to coarse-scale environmental
      features in West Africa. We used ecological niche models to associate Nigerian HP
      H5N1 occurrences with 1 km resolution digital data layers summarizing parameters
      of surface reflectance and landform. Predictive challenges included anticipating
      the spatial distribution of (i) random subsamples and (ii) spatially and
      temporally stratified subsamples of Nigerian occurrence data, and (iii) more
      limited occurrence data from across West Africa. In almost all tests, we found
      that HP-H5N1 cases were occurring under predictable environmental conditions,
      suggesting that elements of the transmission cycle have some form of ecological
      determination, here measured as differences in land-surface reflectance and plant
      phenology through the year. Considerable additional work is needed to establish
      how these differences affect HP-H5N1 transmission.

PMID- 18343471
TI  - Steroidal glycosides from the roots of Cynanchum amplexicaule Sieb. et Zucc.
AB  - Seven new steroidal glycosides (amplexicosides A (4), B (7), C (8), D (9), E
      (10), F (11), and G (12)), along with six known compounds (cynatratoside A (1),
      tylophoside A (2), cynatratoside B (3), glaucogenin A (5), glaucoside A (6), and
      hancoside A (13)) were isolated from the 95% ethanol extract of the roots of
      Cynanchum amplexicaule (Sieb. et Zucc.). Their structures were determined based
      on spectral and chemical evidence. Compound 12 has a 14, 15-secopregnane-type
      skeleton aglycone, which has not been reported in literature.

PMID- 18343472
TI  - Brain-derived neurotrophic factor (BDNF)-like immunoreactivity localization in
      the retina and brain of Cichlasoma dimerus (Teleostei, Perciformes).
AB  - Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in the
      development and maintenance of vertebrate nervous systems. Although there were
      several studies in classical animal models, scarce information for fish was
      available. The main purpose of this study was to analyze the distribution of BDNF
      in the brain and retina of the cichlid fish Cichlasoma dimerus. By
      immunohistochemistry we detected BDNF-like immunoreactive cells in the cytoplasm
      and the nuclei of the ganglion cell layer and the inner nuclear layer of the
      retina. In the optic tectum, BDNF-like immunoreactivity was detected in the
      nucleus of neurons of the stratum periventriculare and the stratum marginale and
      in neurons of the intermediate layers. In the hypothalamus we found BDNF-like
      immunoreactivity mainly in the cytoplasm of the nucleus lateralis tuberis and the
      nucleus of the lateral recess. To confirm the nuclear and cytoplasm localization
      of BDNF we performed subcellular fractionation, followed by Western blot,
      detecting a 39 kDa immunoreactive-band corresponding to a possible precursor form
      of BDNF in both fractions. BDNF-like immunoreactivity was distributed in areas
      related with photoreception (retina), the integration center of retinal
      projections (optic tectum) and the control center of background and stress
      adaptation (hypothalamus). These results provide baseline anatomical information
      for future research about the role of neurotrophins in the adult fish central
      nervous system.

PMID- 18343473
TI  - Modulation of pulmonary inflammatory responses and antimicrobial defenses in mice
      exposed to diesel exhaust.
AB  - Diesel exhaust (DE) is a major component of urban air pollution and has been
      shown to increase the severity of infectious and allergic lung disease. The
      purpose of this study was to evaluate the effects of DE exposure on pulmonary
      inflammation, mediator production and antimicrobial defenses in an exposure model
      that had previously been shown to increase susceptibility to influenza. BALB/c
      mice were exposed to filtered air, or to DE diluted to yield 0.5 or 2 mg/m(3) of
      diesel exhaust particles (DEP) for 4 h per day for 1 or 5 days. Immediately and
      18 h after one or five diesel exposures mice were euthanized to assess both
      immediate and delayed effects. DE exposure for 5 days at either concentration
      caused higher neutrophil numbers and lesion scoring compared to air controls.
      Intracellular adhesion molecule-1 (ICAM-1), which recruits inflammatory cells and
      is an entry site for rhinoviruses was increased immediately after 1 or 5 days of
      DE exposure. Several inflammatory and immune cytokines (TNF-alpha, MIP-2, IL-6,
      IFN-gamma, and IL-13) were also upregulated at various time points and
      concentrations. In contrast, clara cell secretory protein (CCSP), surfactant
      protein A (SP-A), and surfactant protein D (SP-D) which are important host
      defense molecules, were significantly decreased at both the message and protein
      level with DE exposure. We conclude that exposure to moderate and high
      occupational levels of DE caused an increase in lung injury and inflammation, and
      a decrease in host defense molecules, which could result in increased
      susceptibility to respiratory pathogens.

PMID- 18343474
TI  - Phenol used as a preservative in Bothrops antivenom induces impairment in
      leukocyte-endothelial interactions.
AB  - The effect of Bothrops antivenom on blocking the disturbances induced by Bothrops
      jararaca venom in leukocyte-endothelial interactions (LEI) at the
      microcirculation of the cremaster muscle in mice was evaluated using intravital
      microscopy. Our findings showed that an i.v. injection of Bothrops antivenom, per
      se, induced changes in LEI, similar to those induced by an s.c. injection of B.
      jararaca venom, and that Bothrops antivenom can also induce ephemeral symptoms,
      such as tremor and dyspnea in mice. These effects were mostly due to phenol used
      in Bothrops antivenom as a preservative, since animals injected i.v. with a
      phenol solution, but not with phenol-free Bothrops antivenom, presented those
      effects on LEI, and also tremor and dyspnea. In addition, phenol-free antivenom
      abrogated venom-induced changes in LEI parameters. The present data demonstrate
      that Bothrops antivenom contains antibodies that neutralize toxins of B. jararaca
      venom that impair LEI, and suggest that the phenol used as a preservative in it
      can originate some undesired effects.

PMID- 18343475
TI  - Mapping of nucleocapsid residues important for HIV-1 genomic RNA dimerization and
      packaging.
AB  - Retroviral genomic RNA (gRNA) dimerization appears essential for viral
      infectivity, and the nucleocapsid protein (NC) of human immunodeficiency virus
      type 1 (HIV-1) facilitates HIV-1 gRNA dimerization. To identify the relevant and
      dispensable positions of NC, 34 of its 55 residues were mutated, individually or
      in small groups, in a panel of 40 HIV-1 mutants prepared by site-directed
      mutagenesis. It was found that the amino-terminus, the proximal zinc finger, the
      linker, and the distal zinc finger of NC each contributed roughly equally to
      efficient HIV-1 gRNA dimerization. The N-terminal and linker segments appeared to
      play predominantly electrostatic and steric roles, respectively. Mutating the
      hydrophobic patch of either zinc finger, or substituting alanines for their
      glycine doublet, was as disabling as deleting the corresponding finger. Replacing
      the CysX(2)CysX(4)HisX(4)Cys motif of either finger by CysX(2)CysX(4)CysX(4)Cys
      or CysX(2)CysX(4)HisX(4)His, interchanging the zinc fingers or, replacing one
      zinc finger by a copy of the other one, had generally intermediate effects; among
      these mutations, the His23-->Cys substitution in the N-terminal zinc finger had
      the mildest effect. The charge of NC could be increased or decreased by up to
      18%, that of the linker could be reduced by 75% or increased by 50%, and one or
      two electric charges could be added or subtracted from either zinc finger,
      without affecting gRNA dimerization. Shortening, lengthening, or making
      hydrophobic the linker was as disabling as deleting the N-terminal or the C
      terminal zinc finger, but a neutral and polar linker was innocuous. The present
      work multiplies by 4 and by 33 the number of retroviral and lentiviral NC
      mutations known to inhibit gRNA dimerization, respectively. It shows the first
      evidence that gRNA dimerization can be inhibited by: 1) mutations in the N
      terminus or the linker of retroviral NC; 2) mutations in the proximal zinc finger
      of lentiviral NC; 3) mutations in the hydrophobic patch or the conserved glycines
      of the proximal or the distal retroviral zinc finger. Some NC mutations impaired
      gRNA dimerization more than mutations inactivating the viral protease, indicating
      that gRNA dimerization may be stimulated by the NC component of the Gag
      polyprotein. Most, but not all, mutations inhibited gRNA packaging; some had a
      strong effect on virus assembly or stability.

PMID- 18343476
TI  - Walleye dermal sarcoma virus Orf B functions through receptor for activated C
      kinase (RACK1) and protein kinase C.
AB  - Walleye dermal sarcoma virus is a complex retrovirus that is associated with
      walleye dermal sarcomas that are seasonal in nature. Fall developing tumors
      contain low levels of spliced accessory gene transcripts A and B, suggesting a
      role for the encoded proteins, Orf A and Orf B, in oncogenesis. In explanted
      tumor cells the 35 kDa Orf B accessory protein is localized to the cell periphery
      in structures similar to focal adhesions and along actin stress fibers. Similar
      localization was observed in mammalian cells. The cellular protein, receptor for
      activated C kinase 1 (RACK1), bound Orf B in yeast two-hybrid assays and in cell
      culture. Sequence analysis of walleye RACK1 demonstrated high conservation to
      other known RACK1 sequences. RACK1 binds to activated protein kinase C (PKC). Orf
      B associates with PKCalpha, which is constitutively activated and localized at
      the membrane. Activated PKC promoted cell survival, proliferation, and increased
      cell viability in Orf B-expressing cells.

PMID- 18343477
TI  - Hepatitis C virus envelope glycoprotein co-evolutionary dynamics during chronic
      hepatitis C.
AB  - Hepatitis C virus (HCV) envelope glycoprotein co-evolution was studied in 14
      genotype 1-infected and treatment-naive subjects, including 7 with mild and 7
      with severe liver disease. Cassettes encoding the envelope 1 gene (E1) and
      hypervariable region (HVR1) of the envelope 2 gene were isolated at 38 different
      time points over 81 follow-up years. There were no significant differences in
      age, gender, alcohol use, or viral load between the mild and severe disease
      groups. Virus from subjects with severe disease had significantly slower
      evolution in HVR1, and significant divergent evolution of E1 quasispecies,
      characterized by a preponderance of synonymous mutations, compared to virus from
      subjects with mild disease. Phylogenetic comparisons indicated higher similarity
      between amino acid sequences of the E1 and HVR1 regions with mild disease versus
      severe disease (r=0.44 versus r=0.17, respectively; P=0.01). In summary, HCV
      envelope quasispecies co-evolution differs during mild versus severe disease.

PMID- 18343478
TI  - The color appearance of stimuli detected via short-wavelength-sensitive cones:
      comparisons with visual adaptation and visual field data for peri- or post
      menopausal women under 70 years of age.
AB  - Dynamics of foveal light adaptation for vision mediated via short-wavelength
      sensitive (SWS) cones were compared for two groups of healthy amenorrheic (peri-
      or post-menopausal) women not using hormonal medication. Each subject was
      assigned to a group based on the color name-"lavender" ( approximately 2/3 of all
      subjects) or "white" (approximately 1/3 of all subjects)-chosen in a forced
      response paradigm to best describe a threshold-level 440-nm test presented on a
      larger 3.6 log td 580-nm background that had been viewed for approximately 5 min.
      During the first 20-30s after this 3.6 log td background abruptly replaced a much
      dimmer background, the threshold elevations (relative to the steady-state levels
      measured at approximately 5 min) were significantly greater for the lavender
      naming subjects than for the white-naming subjects. However, exponential rates of
      recovery were indistinguishable for the two groups. A viable interpretation is
      that the gain of the visual response at background onset is greater for lavender
      naming subjects than for white-naming subjects at or distal to a site where
      responses from middle-wavelength-sensitive and long-wavelength-sensitive (MWS and
      LWS) cones oppose responses from SWS cones. In addition, the color names derived
      from foveal testing were related systematically to extrafoveal sensitivities
      measured with Short Wavelength Automated Perimetry (SWAP), in a manner suggesting
      that response gain and/or response speed may be greater for lavender-naming
      subjects in the direction of increased SWS response also. Evidence from other
      subject populations suggests that the choice of color name and the dynamics of
      visual response each can be affected by alterations (particularly reductions) of
      estrogen synthesis and response.

PMID- 18343479
TI  - Sensitivity to stimulus onset and offset in the S-cone pathway.
AB  - Previous work [Vassilev, capital A, Cyrillic., Mihaylova, M., Racheva, K.,
      Zlatkova, M., & Anderson, R. S. (2003). Spatial summation of S-cone ON and OFF
      signals: Effects of retinal eccentricity. Vision Research, 43, 2875-2884;
      Vassilev, A., Zlatkova, M., Krumov, A., & Schaumberger, M. (2000). Spatial
      summation of blue-on yellow light increments and decrements in human vision.
      Vision Research, 40, 989-1000] has shown that spatial summation of brief S-cone
      selective stimuli depends on their polarity, increments or decrements, suggesting
      involvement of S-ON and OFF pathways, respectively. This assumption was tested in
      two experiments using a modified two-color threshold method of Stiles to
      selectively stimulate the S-cones. In the first experiment we measured detection
      threshold for small 100ms S-cone selective increments and decrements presented
      within three types of temporal window, rectangular, ramp onset/rapid offset and
      rapid onset/ramp offset. The ramp-onset threshold was higher than the ramp-offset
      threshold regardless of stimulus sign. In the second experiment we measured
      reaction time (RT) with near-threshold stimuli spatially coincident with the
      background to avoid spatial contrast. RT distribution for S-cone selective 500ms
      increments and decrements was unimodal and followed stimulus onset. An increase
      of stimulus duration to 1000 and 2000ms resulted in the appearance of responses
      following stimulus offset. The results suggest that, for brief S-cone selective
      increments or decrements, the human visual system is more sensitive to stimulus
      onset than to stimulus offset. Only for longer stimuli is the offset important,
      probably due to slow adaptation at a postreceptoral level.

PMID- 18343480
TI  - Patterns of spatial distortions in human amblyopia are invariant to stimulus
      duration and instruction modality.
AB  - We investigated the patterns of two-dimensional spatial distortions in human
      amblyopia, using three different psychophysical mapping procedures. Strabismic
      and strabismic-anisometropic amblyopes showed consistent distortions, consisting
      in enlargement, shrinkage, or torsion of portions of the tested visual field.
      Purely anisometropic amblyopes and strabismics with alternating fixation showed
      increased spatial uncertainty, but no consistent distortions. For all groups of
      subjects, there was a very good correspondence between the patterns of distortion
      obtained with the three methods. We conclude that the spatial distortions are
      robust across different procedures. They might reflect a genuine rearrangement of
      the cortical topography as a result of strabismus.

PMID- 18343481
TI  - Photocatalytic bacterial inactivation by polyoxometalates.
AB  - The photocatalytic inactivation (PCI) of Escherichia coli (Gram-negative) and
      Bacillus subtilis (Gram-positive) was performed using polyoxometalate (POM) as a
      homogeneous photocatalyst and compared with that of heterogeneous TiO2
      photocatalyst. Aqueous suspensions of the microorganisms (10(7)-10(8)cfu ml(-1))
      and POM (or TiO2) were irradiated with black light lamps. The POM-PCI was faster
      than (or comparable to) TiO2-PCI under the experimental conditions employed in
      this study. The relative efficiency of POM-PCI was species-dependent. Among three
      POMs (H(3)PW(12)O(40), H(3)PMo(12)O(40), and H(4)SiW(12)O(40)) tested in this
      study, the inactivation of E. coli was fastest with H(4)SiW(12)O(40) while that
      of B. subtilis was the most efficient with H(3)PW(12)O(40). Although the biocidal
      action of TiO2 photocatalyst has been commonly ascribed to the role of
      photogenerated reactive oxygen species such as hydroxyl radicals and superoxides,
      the cell death mechanism with POM seems to be different from TiO2-PCI. While TiO2
      caused the cell membrane disruption, POM did not induce the cell lysis. When
      methanol was added to the POM solution, not only the PCI of E. coli was enhanced
      (contrary to the case of TiO2-PCI) but also the dark inactivation was observed.
      This was ascribed to the in situ production of formaldehyde from the oxidation of
      methanol. The interesting biocidal property of POM photocatalyst might be
      utilized as a potential disinfectant technology.

PMID- 18343482
TI  - Clk-1 deficiency induces apoptosis associated with mitochondrial dysfunction in
      mouse embryos.
AB  - Clk-1 gene encodes demethoxyubiquinone hydroxylase that catalyzes the production
      of coenzyme Q (CoQ) in mitochondria. Clk-1-deficient mice that lack CoQ fail to
      survive beyond the embryonic day 10.5 (E10.5). However, the relationship between
      the clk-1-deficiency and embryonic lethality remains unclear. We show in this
      study that TUNEL-positive cells are frequently observed in whole bodies of clk-1
      deficient mouse embryos at E10.5. In addition, dissociated cells from the embryos
      exhibited characteristic features of apoptosis, such as externalization of
      phosphatidylserine on the plasma membrane, caspase-3 activation, and the release
      of cytochrome c from mitochondria into the cytoplasm, as the first sign of
      mitochondria-mediated apoptosis. In embryonic cells, the mitochondrial functions
      such as maintenance of the mitochondrial membrane potential and intracellular ATP
      level were impaired. Since exogenous CoQ10 rescued the mitochondrial dysfunction
      and suppressed apoptosis in clk-1-deficient cells, we propose that clk-1
      deficiency induces apoptosis associated with mitochondrial dysfunction due to a
      lack of CoQ, which may lead to embryonic lethality in mice around E10.5.

PMID- 18343483
TI  - Molecular basis of the mammalian pressure-sensitive ion channels: focus on
      vascular mechanotransduction.
AB  - Mechano-gated ion channels are implicated in a variety of neurosensory functions
      ranging from touch sensitivity to hearing. In the heart, rhythm disturbance
      subsequent to mechanical effects is also associated with the activation of
      stretch-sensitive ion channels. Arterial autoregulation in response to
      hemodynamic stimuli, a vital process required for protection against hypertension
      induced injury, is similarly dependent on the activity of force-sensitive ion
      channels. Seminal work in prokaryotes and invertebrates, including the nematode
      Caenorhabditis elegans and the fruit fly drosophila, greatly helped to identify
      the molecular basis of volume regulation, hearing and touch sensitivity. In
      mammals, more recent findings have indicated that members of several structural
      family of ion channels, namely the transient receptor potential (TRP) channels,
      the amiloride-sensitive ENaC/ASIC channels and the potassium channels K2P and Kir
      are involved in cellular mechanotransduction. In the present review, we will
      focus on the molecular and functional properties of these channel subunits and
      will emphasize on their role in the pressure-dependent arterial myogenic
      constriction and the flow-mediated vasodilation.

PMID- 18343484
TI  - Relationship between prostatic urethral angle and urinary flow rate: its
      implication in benign prostatic hyperplasia pathogenesis.
AB  - OBJECTIVES: The prostatic urethra is a bent tube, and the clinical significance
      of the prostatic urethral angle (PUA) is poorly understood. We investigated the
      effect of the PUA on the urinary flow rate in men without benign prostatic
      obstruction. METHODS: In a theoretical model, the urinary flow rate at the end of
      the prostatic urethra was formulated according to some principles of fluid
      dynamics, including the Navier-Storkes equation, Bernoulli's equation, and the
      loss of coefficient at bends. The change in the urinary flow rate according to
      the PUA was also calculated through mathematical simulations. In addition, the
      relationship between the PUA and the peak flow rate was evaluated in 65 healthy
      men without benign prostatic obstruction (age 50 to 59 years, prostate volume
      less than 30 cm(3), peak flow rate greater than 15 mL/s). The prostate volume and
      PUA were determined by transrectal ultrasonography. RESULTS: Using the fluid
      dynamic model, the urinary flow rate increased in proportion to the urethral
      diameter and was inversely associated with the PUA. The mathematical simulations
      showed that the urinary flow rate decreased by more than 27% as the PUA increased
      from 35 degrees to 90 degrees. In the clinical setting, the peak flow rate was
      significantly associated with the PUA by linear regression analysis (R = 0.34,
      beta = -0.342, P = 0.005), but it was not associated with the total prostate
      volume (R = 0.18, beta = -0.181, P = 0.150). CONCLUSIONS: The PUA was inversely
      associated with the urinary flow rate in this theoretical model and preliminary
      clinical study. This relationship could be an important factor in the
      pathogenesis of benign prostatic hyperplasia/lower urinary tract symptoms.

PMID- 18343485
TI  - Retroperitoneal cold abscess caused by mycobacteria chelonae abscessus after
      percutaneous nephrolithotomy in India: strategies for detection, management, and
      prevention in the United States.
AB  - Atypical, nontuberculous, mycobacteria (NTM) are emerging as significant
      pathogens in nosocomial infections. Historically, such outbreaks have been
      limited to developing countries, and clinicians in the United States have not
      been exposed to the nuances of diagnosing and treating such infections. With an
      increasing prevalence worldwide, all clinicians should be able to recognize and
      treat NTM infections. We report a case of a patient who developed a
      retroperitoneal cold abscess caused by NTM after percutaneous stone surgery in
      India. Through a comprehensive review of published reports, we offer strategies
      for the treatment and prevention of such outbreaks.

PMID- 18343486
TI  - Modern management of adult-acquired buried penis.
AB  - OBJECTIVES: To report our successful experience in managing acquired adult buried
      penis from nontraumatic origins. We describe a combination of modern techniques
      involving escutcheonectomy, scrotoplasty, split-thickness skin graft, and fibrin
      sealant application for genital reconstruction. METHODS: From 2004 through 2007,
      5 men with acquired adult buried penis underwent surgical repair at our medical
      center, by a single surgeon. A buried penis was a result of obesity in 4 of 5
      patients, although other complicating factors, such as scrotal lymphedema, lichen
      sclerosis, and peripenile woody induration, were present in 3 of the 5 patients.
      All 5 patients required scrotoplasty and split-thickness skin grafts fastened
      with dilute fibrin glue to cover the penile skin defects. Excision of the
      excessive suprapubic fat pad (escutcheonectomy) was performed in the 4 obese
      patients. RESULTS: All patients achieved excellent cosmetic results, with
      successful and lasting unburying achieved in all cases. The operative difficulty,
      intraoperative blood loss, and length of hospital stay varied. No wound
      complications developed at the skin donor sites, and a rate of 80% to 100% graft
      take was observed on the penis at 2 months postoperatively. Abdominal wound
      complications were noted in 2 patients and resolved with daily dressing changes.
      CONCLUSIONS: Acquired adult buried penis is a correctable problem. The use of
      combined techniques, including surgical unburying, scrotoplasty,
      escutcheonectomy, and split-thickness skin grafts fixed with dilute fibrin glue,
      appears to be a useful approach to repair this unique condition.

PMID- 18343487
TI  - Prognostic role of Ca125 response criteria and RECIST criteria: analysis of
      results from the MITO-3 phase III trial of gemcitabine versus pegylated liposomal
      doxorubicin in recurrent ovarian cancer.
AB  - OBJECTIVES: The aim of the study was to investigate i) the association between
      the Ca125 based and the RECIST assessed response in recurrent ovarian cancer
      patients enrolled in a Phase III randomized trial (MITO-3) comparing salvage
      treatment with pegylated liposomal doxorubicin (PLD) versus gemcitabine (GEM);
      ii) the correlation between the early modifications of Ca125 levels during
      treatment and the RECIST assessed response; iii) the prognostic value of response
      based on Ca125 and the RECIST criteria. METHODS: Assessment of response was
      performed by the RECIST and the GCIG criteria. The prognostic impact of the
      response by the RECIST criteria and the GCIG criteria was analyzed by the
      landmark method. RESULTS: Overall, of 30 cases defined as responders on the basis
      of the GCIG criteria, 20 resulted as responders according to the RECIST criteria
      (NPV=66.7%); conversely, 93.7% of the cases considered not responders based on
      the GCIG criteria were defined as unresponsive at RECIST evaluation. Early
      modifications of Ca125 levels were not completely predictive of the ultimate
      RECIST defined response. Overall survival (OS) was longer in RECIST defined
      responders versus non responders, although the statistical significance was not
      reached (p value=0.092); conversely, median OS was significantly longer in GCIG
      defined responders than in non responding patients (p value=0.0059). In
      multivariate analysis, the GCIG assessed response maintained its independent
      association with OS. CONCLUSIONS: GCIG criteria for tumor response could replace
      the conventional assessment of response in the decision making process relative
      to the discontinuation or prolongation of the salvage treatment in ovarian
      cancer.

PMID- 18343489
TI  - Exploitation of HIV protease inhibitor Indinavir as a memory restorative agent in
      experimental dementia.
AB  - The present study was undertaken to investigate the beneficial effect of HIV
      protease inhibitor Indinavir on memory deficits associated with experimental
      dementia of Alzheimer disease's (AD) type. Dementia was induced in Swiss albino
      mice by administration of Celecoxib (100 mg kg(-1) orally, daily for 9 days) or
      Streptozotocin (3 mg kg(-1) administered intracerebroventricularly on 1st and 3rd
      day) and the cognitive behaviors of Swiss albino mice were assessed using Morris
      water maze test. Brain acetyl cholinesterase (AChE) activity was measured by Ell
      Mann's method. Brain thiobarbituric acid reactive species (TBARS) levels and
      reduced glutathione (GSH) levels were measured by Ohokawa's and Beutler's method
      respectively to assess total oxidative stress. Donepezil (0.1 mg kg(-1) i.p.)
      served as positive control in the present investigation. Celecoxib as well as
      Streptozotocin (STZ) produced a significant loss of learning and memory.
      Indinavir (100 and 200 mg kg(-1) orally) successfully attenuated Celecoxib as
      well as STZ induced cognitive deficits. Higher levels of brain AChE activity,
      TBARS and lower levels of GSH were observed in Celecoxib as well as STZ treated
      animals, which were significantly attenuated by Donepezil and Indinavir. Study
      highlights the potential of Indinavir in memory dysfunctions associated with
      dementia of AD.

PMID- 18343488
TI  - Characteristics of membrane progestin receptor alpha (mPRalpha) and progesterone
      membrane receptor component 1 (PGMRC1) and their roles in mediating rapid
      progestin actions.
AB  - Rapid, progestin actions initiated at the cell surface that are often nongenomic
      have been described in a variety of reproductive tissues, but until recently the
      identities of the membrane receptors mediating these nonclassical progestins
      actions remained unclear. Evidence has been obtained in the last 4-5 years for
      the involvement of two types of novel membrane proteins unrelated to nuclear
      steroid receptors, progesterone membrane receptors (mPRs) and progesterone
      receptor membrane component 1 (PGMRC1), in progestin signaling in several
      vertebrate reproductive tissues and in the brain. The mPRs, (M(W) approximately
      40 kDa) initially discovered in fish ovaries, comprise at least three subtypes,
      alpha, beta and gamma and belong to the seven-transmembrane progesterone
      adiponectin Q receptor (PAQR) family. Both recombinant and wildtype mPRs display
      high affinity (K(d) approximately 5 nM), limited capacity, displaceable and
      specific progesterone binding. The mPRs are directly coupled to G proteins and
      typically activate pertussis-sensitive inhibitory G proteins (G(i)), to down
      regulate adenylyl cyclase activity. Recent studies suggest the alpha subtype
      (mPRalpha) has important physiological functions in variety of reproductive
      tissues. The mPRalpha is an intermediary in progestin induction of oocyte
      maturation and stimulation of sperm hypermotility in fish. In mammals, the
      mPRalphas have been implicated in progesterone regulation of uterine function in
      humans and GnRH secretion in rodents. The single-transmembrane protein PGMRC1
      (M(W) 26-28 kDa) was first purified from porcine livers and its cDNA was
      subsequently cloned from porcine smooth muscle cells and a variety of other
      tissues by different investigators. PGMRC1 and the closely-related PGMRC2 belong
      to the membrane-associated progesterone receptor (MAPR) family. The PGMRC1
      protein displays moderately high binding affinity for progesterone which is 2- to
      10-fold greater than that for testosterone and glucocorticoids, and also can bind
      to other molecules such as heme, cholesterol metabolites and proteins. The signal
      transduction pathways induced by binding of progesterone to PGMRC1 have not been
      described to date, although motifs for tyrosine kinase, kinase binding, SH2 and
      SH3 have been predicted from the amino acid sequence. Evidence has been obtained
      that PGMRC1 mediates the antiapoptotic affects of progesterone in rat granulosa
      cells. The PGMRC1 protein may also be an intermediary in the progesterone
      induction of the acrosome reaction in mammalian sperm. Despite these recent
      advances, many aspects of progestin signaling through these two families of novel
      membrane proteins remain unresolved. Biochemical characterization of the
      receptors has been hampered by rapid degradation of the partially purified
      proteins. A major technical challenge has been to express sufficient amounts of
      the recombinant receptors on the plasma membranes in eukaryotic systems to permit
      investigations of their progestin binding and signal transduction
      characteristics. Additional basic information on the molecular and cellular
      mechanisms by which mPRs and PGMRC1 interact with progestins, signal
      transductions pathways and other proteins will be required to establish a
      comprehensive model of nontraditional progestin actions mediated through these
      novel proteins.

PMID- 18343490
TI  - Effects of epigallocatechin-3-gallate (EGCG) on in vitro maturation and
      fertilization of porcine oocytes.
AB  - The beneficial properties of green tea and especially of its principal active
      polyphenol, epigallocatechin-3-gallate (EGCG), have led to an increased demand
      for dietary supplements with highly enriched EGCG concentrations. In order to
      investigate the possible reproductive-related consequence of EGCG
      supplementation, the effects of this catechin on in vitro maturation (IVM) and
      fertilization (IVF) of oocyte, using the pig as experimental model, were
      examined. In the first series of experiments EGCG, at concentrations ranging from
      0 to 25 microg/ml, was added during in vitro maturation of pig oocytes. EGCG had
      no effect on nuclear maturation of pig oocytes and on fertilization traits
      considered after IVF at any of the doses tested. By contrast, a significant
      (p<0.05) decrease in the number of embryos that developed to blastocysts
      following parthenogenetic activation was recorded when 25 microg/ml EGCG was
      added to IVM medium; in addition this catechin concentration significantly
      (p<0.05) inhibited progesterone production by cumulus cells after 48 h of
      culture. When induction of sperm capacitation was performed in presence of EGCG,
      a significantly lower percentage of spermatozoa showing a Hsp70-capacitated
      pattern and a significant reduction of sperm H(2)O(2) production were evident at
      a concentration of 25 microg/ml EGCG (p<0.05). During gamete coincubation EGCG
      reduced, in a dose response manner, the number of reacted spermatozoa suspended
      in fertilization medium and increased the number of sperm bound to ZP.
      Supplementation of 10 microg/ml EGCG during IVF significantly increased the
      fertilization rate while higher EGCG concentrations (25 microg/ml) decreased the
      percentage of fertilized oocytes (p<0.05). In conclusion, our data suggest that
      high EGCG concentrations could affect in vitro maturation and fertilization in
      pig; it cannot be totally excluded that excessive EGCG concentrations could
      induce reproductive-related consequences also in vivo.

PMID- 18343491
TI  - History of commercializing sexed semen for cattle.
AB  - Although the basic principles controlling the sex of mammalian offspring have
      been known for a relatively long time, recent application of certain modern
      cellular methodologies has led to development of a flow cytometric system capable
      of differentiating and separating living X- and Y-chromosome-bearing sperm in
      amounts suitable for AI and therefore, commercialization of this sexing
      technology. After a very long history of unsuccessful attempts to differentiate
      between mammalian sperm that produce males from those that produce females, a
      breakthrough came in 1981 when it was demonstrated that precise DNA content could
      be measured. Although these initial measurements of DNA content killed the sperm
      in the process, they led to the ultimate development of a sperm sorting system
      that was capable, not only of differentiating between live X- and Y-sperm, but of
      sorting them into relatively pure X- and Y-sperm populations without obvious
      cellular damage. Initial efforts to predetermine the sex of mammalian offspring
      in 1989 required surgical insemination, but later enhancements provided sex
      sorted sperm in quantities suitable for use with IVF. Subsequent advances in flow
      sorting provided minimal numbers of sperm sufficient for use in AI. It was not
      until the flow cytometric sorting system was improved greatly and successful
      cryopreservation of sex-sorted bull sperm was developed that efficacious
      approaches to commercialization of sexed semen could be implemented worldwide in
      cattle. A number of companies now offer sex-sorted bovine sperm. Innovative
      approaches by a diverse group of scientists along with advances in computer
      science, biophysics, cell biology, instrumentation, and applied reproductive
      physiology provided the basis for commercializing sexed semen in cattle.

PMID- 18343492
TI  - Environmental constrains on post-partum ovarian activity in Tanzanian Zebu cows.
AB  - Milk progesterone measurements were used to study post-partum ovarian activity
      and risk factors for ovarian dysfunction in Zebu cows reared under a traditional
      pastoral management system in three villages in Morogoro region, Tanzania. Milk
      samples for progesterone analysis were collected twice per week from a total of
      98 lactations. The most prevalent ovarian dysfunction detected was delayed onset
      of post-partum ovarian activity and cessation of cyclical ovarian activity after
      a period of normal ovarian function. Prolonged luteal phases were not observed.
      Resumption of post-partum ovarian activity was observed in 61 (62.2%) cows.
      Pregnancy was diagnosed in 43 (43.8%) out of 98 cows and was terminated by
      abortion in 7 (16.3%) cows. The median number of days from calving to resumption
      of ovarian activity was lower in cows that calved during the dry season (167
      days) as compared with those that calved in the rainy season (200 days, P=0.03),
      probably because ovarian function was stimulated in cows entering the rainy
      season first after the puerperal phase had ended. Cyclical ovarian activity
      ceased in seven (11.5%) cows, and all but one case of cessation of ovarian
      activity took place during the dry season. Cows in their first and second
      parities experienced prolonged intervals (244 days) between calving and onset of
      ovarian activity compared with cows in their third or later parity (172 days,
      P=0.03). Cows with marked losses in body condition experienced prolonged
      intervals between calving and onset of ovarian activity (229 days) as compared
      with cows that lost <1 body condition unit (172 days, P=0.03). The time interval
      from calving to resumption of ovarian activity varied between the three villages
      of the study (142, 192 and 229 days, P=0.05), indicating local differences in
      management practices.

PMID- 18343493
TI  - Relative influence of musical and linguistic experience on early cortical
      processing of pitch contours.
AB  - To assess domain specificity of experience-dependent pitch representation we
      evaluated the mismatch negativity (MMN) and discrimination judgments of English
      musicians, English nonmusicians, and native Chinese for pitch contours presented
      in a nonspeech context using a passive oddball paradigm. Stimuli consisted of
      homologues of Mandarin high rising (T2) and high level (T1) tones, and a linear
      rising ramp (T2L). One condition involved a between-category contrast (T1/T2),
      the other, a within-category contrast (T2L/T2). Irrespective of condition,
      musicians and Chinese showed larger MMN responses than nonmusicians; Chinese
      larger than musicians. Chinese, however, were less accurate than nonnatives in
      overt discrimination of T2L and T2. Taken together, these findings suggest that
      experience-dependent effects to pitch contours are domain-general and not driven
      by linguistic categories. Yet specific differences in long-term experience in
      pitch processing between domains (music vs. language) may lead to gradations in
      cortical plasticity to pitch contours.

PMID- 18343494
TI  - Influence of filler on the difference between the transmitted and reflected
      colors of experimental resin composites.
AB  - OBJECTIVES: This study sought to determine the influence of filler size and
      amount on the difference between the transmitted and reflected colors and the
      translucency of experimental resin composites. METHODS: The color of experimental
      resin composites (38 mm in diameter and 1 mm in thickness) was measured in the
      transmittance and reflectance modes. Opalescence parameter (OP) was calculated as
      the difference in blue-yellow and red-green coordinates between the transmitted
      and reflected colors. Translucency parameter (TP) was calculated as the color
      difference between the reflected colors over a white and a black background.
      RESULTS: The range of OP was between 1.0 and 5.7, which was varied by the size
      and amount of filler. TP decreased as the amount of filler increased when the
      filler size was the same. SIGNIFICANCE: Controls on the proper filler size and
      amount should be studied further to modify the opalescence and translucency of
      resin composites, considering also the effect of filler on mechanical properties.

PMID- 18343495
TI  - Metallothioneins and cytosolic metals in Neomysis integer exposed to cadmium at
      different salinities.
AB  - In the present study the induction of metallothioneins (MTs) and its relation to
      cytosolic metal concentrations (Zn, Cu and Cd) in the euryhaline crustacean
      Neomysis integer exposed to Cd at different salinities was studied. N. integer
      was exposed to the same free cadmium ion activity of 5.74 x 10(-9) mol l(-1)
      (i.e. 1/5 of the 96 h LC(50) value expressed as cadmium activity) in hypo-osmotic
      (5 psu), isosmotic (16 psu) and hyper-osmotic media (25 psu) for 7 days. In this
      way, the effect of salinity on cadmium speciation was eliminated and therefore
      the physiological effect of salinity on Cd accumulation and MT induction could be
      studied. The accumulation of cytosolic Cd in N. integer changed with salinity
      from 1.11+/-0.05 micromol l(-1) at 5 psu up to 1.43+/-0.17 micromol l(-1) at 25
      psu. This could indicate that the physiological response of euryhaline estuarine
      invertebrates like N. integer to salinity changes can influence the rate of trace
      metal uptake from solution. While the salinity changes did not cause significant
      differences in cytosolic Zn concentrations (mean value of all tested salinities:
      34.4+/-2.8 micromol l(-1)), an inverse relationship between salinity and
      cytosolic Cu concentration was observed. The highest concentration of 15.7+/-2.3
      micromol Cul(-1) was determined at 5 psu and the lowest 10.9+/-1.4 micromol Cul(
      1) at 25 psu. This could point to a possible relationship between the copper
      concentration and the hemocyanin metabolism in N. integer. This is the first time
      that differential pulse voltammetry method was applied to MT assays with N.
      integer. Although the exposure to Cd resulted in a higher Cd cytosolic
      concentration, no subsequent MT increase was detected. The significant positive
      correlation between MT levels and cytosolic Cu concentrations (Spearman
      correlation coefficient r(s)=0.356, p=0.009) implies a strong relationship
      between MT and Cu in N. integer.

PMID- 18343496
TI  - Expression of Keratin 8 and TNF-Related Apoptosis-I Inducing Ligand (TRAIL) in
      Down Syndrome Placentas.

PMID- 18343497
TI  - Crustin expression following bacterial injection and temperature change in the
      shore crab, Carcinus maenas.
AB  - The expression of carcinin, a crustin-type antimicrobial protein, in the crab,
      Carcinus maenas, was studied following in vivo challenge with Planococcus
      citreus, a Gram-positive bacterium known to be killed by the encoded protein.
      Real-time PCR analyses reveal that injection of P. citreus failed to elicit any
      significant changes in expression at 0-24h post-injection although there was a
      small, but significant, down-regulation at 84h in crabs held at 15 degrees C but
      not those at 5 or 20 degrees C. By contrast, un-injected crabs held at various
      temperatures between 5 and 20 degrees C, showed significantly up-regulated
      expression at 5 and at 20 but not 10 degrees C compared with controls at 15
      degrees C. Thus expression of carcinin seems to be affected by temperature,
      especially when the animal is close to the edges of its physiologically tolerated
      thermal range.

PMID- 18343498
TI  - The liberal state and the rogue agency: FDA's regulation of drugs for mood
      disorders, 1950s-1970s.
AB  - The theory of the liberal state does not generally contemplate the possibility
      that regulatory agencies will turn into "rogues," regulating against the
      interests of their clients and, indeed, the public interest. In the years between
      circa 1955 and 1975 this seems to have happened to one of the prime regulatory
      agencies of the US federal government: the Food and Drug Administration (FDA).
      Intent upon transforming itself from a traditional "cop" agency to a regulatory
      giant, the FDA campaigned systematically to bring down some safe and effective
      drugs. This article concentrates on hearings in the area of psychopharmacology
      regarding several antianxiety drugs, namely meprobamate (Miltown),
      chlordiazepoxide (Librium) and diazepam (Valium). In addition, from 1967 to 1973
      this regulatory vengefulness occurred on a broad scale in the Drug Efficacy Study
      Implementation (DESI), an administrative exercise that removed from the market
      almost half of the psychopharmacopoeia. The article explores possible
      bureaucratic motives for these actions.

PMID- 18343499
TI  - The innate pattern recognition molecule Ficolin-1 is secreted by
      monocytes/macrophages and is circulating in human plasma.
AB  - Ficolin-1 (M-Ficolin) is a pattern recognition molecule of the complement system
      that is expressed by myeloid cells and type II alveolar epithelial cells. Ficolin
      1 has been shown to localize in the secretory granules of these cells and
      attached to cell surfaces, but whether Ficolin-1 exists a soluble molecule in the
      extracellular environment or in plasma is unknown. In this study we explored the
      possibility that Ficolin-1 may be secreted from monocytes, macrophages or
      immature dendritic cells and may exist in human plasma. Expression of Ficolin-1
      was analyzed using real-time quantitative PCR and SDS-PAGE/western blot.
      Secretion of Ficolin-1 was investigated in cells and plasma from healthy donors
      through affinity purification using N-acetyl-d-glucosamine-agarose beads and
      ELISA. Ficolin-1 was found differentially expressed and synthesised by monocytes,
      macrophages and immature dendritic cells. Notably monocytes and macrophages, but
      not immature dendritic cells are able to secrete Ficolin-1 into the extracellular
      environment. Moreover, Ficolin-1 was detected in human plasma from healthy donors
      with a median concentration of 60.5 ng/ml ranging from 45.7 to 100.4 ng/ml. We
      show that Ficolin-1 is secreted into the extracellular environment from human
      monocytes/macrophages, but not immature dendritic cells. Importantly, these
      results demonstrate that Ficolin-1 exists in human plasma and serum under normal
      conditions, hereby revising the general assumption that Ficolin-1 is solely a
      cellular associated protein.

PMID- 18343500
TI  - A novel ML protein from Manduca sexta may function as a key accessory protein for
      lipopolysaccharide signaling.
AB  - Lipopolysaccharide (LPS) present on the outer membrane of Gram-negative bacteria
      is one of the most important pathogen-associated molecular patterns and a potent
      elicitor in innate immunity. In human, TLR4 (Toll-like receptor 4) and MD-2
      (myeloid differiation-2) form a receptor complex to transduce the LPS signal into
      cells. However, in invertebrates, receptors that recognize LPS have not been
      determined. Here we report the purification, characterization and cDNA cloning of
      an ML (MD-2-related lipid-recognition) protein from the tobacco hornworm Manduca
      sexta. The full-length cDNA of this M. sexta ML protein, named MsML-1, is 532bp
      with an open reading frame of 456bp that encodes a polypeptide of 151 amino acids
      containing an ML domain. MsML-1 is a secreted glycoprotein and its mRNA is
      expressed in fat body and hemocytes. The expression level of MsML-1 mRNA in fat
      body and hemocytes as well as MsML-1 protein in hemolymph are not induced by
      immune challenge. Recombinant MsML-1 protein specifically binds to LPS from
      several Gram-negative bacteria and LPS Re mutant, as well as to lipid A, but not
      to KDO (2-keto-3-deoxyoctonate). Our results suggest that MsML-1 may function as
      a key accessory protein for LPS signaling in M. sexta against Gram-negative
      bacterial infection.

PMID- 18343501
TI  - Interaction of SIGNR1 expressed by marginal zone macrophages with marginal zone B
      cells is essential to early IgM responses against Streptococcus pneumoniae.
AB  - The spleen plays a pivotal role in the immune defense against encapsulated
      bacteria such as Streptococcus pneumoniae. Murine splenic marginal zone
      macrophages express the C-type lectin SIGNR1, which is crucial for the capture of
      S. pneumoniae from blood. In this study, we demonstrate that SIGNR1 is able to
      interact in vitro with the juxtaposing marginal zone B cell population, which is
      responsible for the production of the early IgM response against the S.
      pneumoniae-epitope phosphorylcholine. Strikingly, SIGNR1-deficient mice display a
      reduction in the marginal zone B cell population. In addition, ex vivo B cell
      stimulation assays demonstrate a decrease in phosphorylcholine specificity in the
      splenic B cell population derived from SIGNR1-deficient mice, whereas the total
      IgM response is unaffected. Therefore, we hypothesize that antigens are presented
      by SIGNR1 expressed by marginal zone macrophages to the developing marginal zone
      B cell population thereby influencing the repertoire of this B cell population,
      which is pivotal for the early immune response against encapsulated bacteria such
      as S. pneumoniae.

PMID- 18343502
TI  - Rapamycin suppresses TLR4-triggered IL-6 and PGE(2) production of colon cancer
      cells by inhibiting TLR4 expression and NF-kappaB activation.
AB  - Toll-like receptor 4 (TLR4) signaling in tumor cells can mediate tumor cell
      immune escape and tumor progression, being regarded as one of the mechanisms for
      chronic inflammation in tumorigenesis and progression. So, intervention of TLR4
      mediated immune escape and metastasis has been proposed as one of the approaches
      to cancer prevention and treatment. Rapamycin, an immunosuppressant agent widely
      used for treatment of autoimmune diseases and transplantation rejection, is
      recently used for cancer therapy. However, the underlying mechanisms remain to be
      fully understood. In the present study, we demonstrate that rapamycin can
      significantly inhibit TLR4-triggered IL-6 and PGE(2) production and invasion of
      colon cancer cells. Suppression of TLR4-induced IL-6 and PGE(2) production is
      responsible for the rapamycin-mediated decrease of TLR4-evoked invasion of colon
      cancer cells. Furthermore, disruption of NF-kappaB pathway contributes to the
      inhibition of TLR4-induced IL-6, PGE(2) production and invasion by rapamycin in
      colon cancer cells. Rapamycin can also downregulate TLR4 expression. Therefore,
      we demonstrate that rapamycin may abrogate TLR4-triggered tumor cell immune
      escape and invasion by downregulating TLR4 expression and inhibiting TLR4
      activated NF-kappaB pathway, thus providing new mechanistic explanation for the
      antitumor effect of rapamycin.

PMID- 18343503
TI  - Alkaline transition of pseudoazurin Met16X mutant proteins: protein stability
      influenced by the substitution of Met16 in the second sphere coordination.
AB  - Several blue copper proteins are known to change the active site structure at
      alkaline pH (alkaline transition). Spectroscopic studies of Met16Phe, Met16Tyr,
      Met16Trp, and Met16Val pseudoazurin variants were performed to investigate the
      second sphere role through alkaline transition. The visible electronic absorption
      and resonance Raman spectra of Met16Phe, Met16Tyr, and Met16Trp variants showed
      the increasing of axial component at pH approximately 11 like wild-type PAz. The
      visible electronic absorption and far-UV CD spectra of Met16Val demonstrated that
      the destabilization of the protein structure was triggered at pH>11. Resonance
      Raman (RR) spectra of PAz showed that the intensity-weighted averaged Cu-S(Cys)
      stretching frequency was shifted to higher frequency region at pH approximately
      11. The higher frequency shift of Cu-S(Cys) bond is implied the stronger Cu
      S(Cys) bond at alkaline transition pH approximately 11. The visible electronic
      absorption and far-UV CD spectra of Met16X PAz revealed that the Met16Val variant
      is denatured at pH>11, but Met16Phe, Met16Tyr, and Met16Trp mutant proteins are
      not denatured even at pH>11. These observations suggest that Met16 is important
      to maintain the protein structure through the possible weak interaction between
      methionine -SCH3 part and coordinated histidine imidazole moiety. The
      introduction of pi-pi interaction in the second coordination sphere may be
      contributed to the enhancement of protein structure stability.

PMID- 18343504
TI  - Microbiology investigations in community acquired pneumonia--most laboratories in
      England and Wales do not offer all those recommended in the British Thoracic
      Society guideline.

PMID- 18343505
TI  - Prevalence of hepatitis C virus in the Mexican population: a systematic review.
AB  - BACKGROUND: Although hepatitis C virus (HCV) infection is considered a relevant
      public health problem in Mexico, the prevalence is still under discussion. The
      objective of this study was to conduct a systematic review to explore the
      prevalence of HCV infection in the Mexican population. METHODS: A systematic
      review of studies reporting prevalence in Mexican population was performed using
      several free-access databases. RESULTS: Sixty-eight works fulfilled the search
      criteria. From these, 44 studies involved asymptomatic subjects and 28 involved
      patients or high-risk subjects. Prevalence of blood donors (6,955,558 persons)
      ranged from 0.0% to 2.05%, with 7/32 studies reporting values >1%, whereas
      prevalence of non-donor asymptomatic subjects (28,528 persons) from 0.0% to 2.7%,
      with 7/11 studies reporting values >1%, and medical personnel from 0.0% to 2.08%
      (1,227 persons), with 4/11 studies reporting values >1%. Prevalence of patients
      with chronic hepatic disease ranged from 6.7% to 77%. The most prevalent genotype
      was 1 (30.0-87.5%), of which subtype 1b is the most frequent (11.9-61.9%). The
      main risk factors were blood transfusion and unprotected sex or having multiple
      sex partners. CONCLUSIONS: The prevalence in the Mexican population seems to be
      in accordance with that previously estimated by the World Health Organization (1
      2.5%).

PMID- 18343506
TI  - Cholinergic modulation of midbrain dopaminergic systems.
AB  - Dopamine neurons in the midbrain respond to behavioral events and environmental
      stimuli. Their different patterns of activation in turn modulate the activity of
      forebrain regions and modulate the expression of selective behavioral responses.
      However, their activity is closely dependent on the cholinergic systems in the
      brainstem. Ascending cholinergic projections from the pedunculopontine and
      laterodorsal tegmental nuclei target dopaminergic neurons in the substantia nigra
      compacta and ventral tegmental area following a topographical gradient. These
      projections, by means of the activation of acetylcholine receptors, influence the
      firing of dopamine neurons and therefore their responsiveness, ultimately
      affecting the release of dopamine in their forebrain targets. Brainstem
      cholinergic neurons are thus in a position to critically influence the activity
      of dopaminergic neurons in the midbrain, and thereby have a critical role in the
      expression of behavior.

PMID- 18343507
TI  - Association between activation of phase 2 enzymes and down-regulation of
      dendritic cell maturation by c9,t11-conjugated linoleic acid.
AB  - Antioxidant and cytoprotective enzymes (phase 2) exert protective activity
      against reactive oxygen species (ROS)-induced injury. We have recently shown how
      the beneficial effects of conjugated linoleic acid (CLA) in a mouse model of an
      autoimmune disease are parallel with the activation of phase 2 enzymes. In the
      present study we found that c9,t11-CLA isomer activates cytoprotective enzymes
      and down-regulates LPS- or gliadin-induced maturation in dendritic cells (DCs)
      obtained from a murine model of celiac disease. As expected, the enhancement of
      LPS-induced maturation (increased NFkappaB p65 nuclear translocation, CD86
      expression and decreased CD11c+ cell number) was exacerbated by specific
      glutathione (GSH) inhibitor (buthionine sulphoximine; BSO). Conversely, the down
      regulation of DC maturation by antioxidant N-acetylcysteine (NAC) was associated
      with the marked increase of intracellular thiol concentration. c9,t11-CLA
      activation of phase 2 enzymes in mouse DCs was observed first. Next, we found
      that the significant reduction of LPS- and gliadin-induced DC maturation in
      cultures pre-treated with c9,t11-CLA improved cellular redox status (decreased
      ROS and higher antioxidant defenses). Finally, the process of DC maturation
      triggered by gliadin, in contrast with that exhibited by LPS, was not associated
      with enhanced NFkappaB nuclear translocation and pro-inflammatory cytokines
      synthesis. These results demonstrate that c9,t11-CLA renders DCs more resistant
      to gliadin- or LPS-induced maturation, thus indicating that a cytoprotective
      mechanism elicited by c9,t11-CLA may modulate DC responsiveness.

PMID- 18343508
TI  - Neurological complications of celiac disease and autoimmune mechanisms: a
      prospective study.
AB  - Humoral immune mechanisms may have a role in the neurological complications of
      celiac disease (CD). We assessed 71 CD patients for neurologic manifestations and
      presence of serum antibodies to neural antigens. Sixteen patients (22.5%) were
      found to have neurological deficits including headache, depression, entrapment
      syndromes, peripheral neuropathy, and epilepsy. Antibody reactivity to neural
      antigens was detected in 30/71 (42.2%) patients. There was no clear correlation
      between anti-neural reactivity and neurologic dysfunction. Follow-up of 62
      patients did not reveal change in electrophysiology or antibodies, regardless of
      diet. However, in 2 patients with neuropathy, symptoms improved or worsened
      depending on the diet.

PMID- 18343509
TI  - Neuropeptide Y receptor-specifically modulates human neutrophil function.
AB  - Despite a continuously growing body of evidence highlighting the role of NPY in
      the immune system, surprisingly little is known about its ability to alter human
      leukocyte function. We therefore set out to examine NPY receptor expression and
      functional effects of NPY in freshly isolated human neutrophils. Our results not
      only demonstrate for the first time the presence of specific NPY receptors on
      human neutrophils, but also unveil of how these receptors differentially modulate
      critical functions of neutrophils such as phagocytosis of bacteria as well as the
      release of reactive oxygen species.

PMID- 18343510
TI  - Evaluation of hearing organ in patients with Turner syndrome.
AB  - Hearing loss and middle ear diseases are often reported in some of Turner
      patients. In most of the reports hearing organ was evaluated with the use of
      subjective methods. The aim of the work was subjective and objective evaluation
      of hearing organ with an attempt to set the correlation between the results and
      the genotype of the patients with Turner syndrome (Ts). MATERIAL: 51 Ts patients
      aged 14.3 years on average. There were 29 girls with monosomy X and 22 having
      mosaicism. A detailed medical history was taken in each case with attention given
      to the hearing loss risk factors. METHOD: Physical ENT examination, hearing
      evaluation: pure tone audiometry, impedance audiometry, distortion products
      otoacoustic emissions (DPOAEs), brain auditory evoked potentials (BAEP). The
      control group consisted of 30 healthy patients. RESULTS: Recurrent acute otitis
      media was reported by 19.6% of Ts patients. Pure tone audiometry was improper in
      36.3% ears; conductive hearing loss was present in 11.7% ears, mixed hearing loss
      in 5.9% ears and the moderate sensorineural hearing loss in 18.6% ears. Impedance
      audiometry was impaired in 14.7% of the cases. DPOAE disturbances were present in
      41.4% of Ts patients, BAEP was improper in 52.0%. The percentage of the
      disturbances in DOPAEs and in BAEP in patients with mosaicism was 45.4 and 40.9%
      while in patients with monosomy 68.9 and 62%. CONCLUSIONS: Ts patients present
      predisposition to hearing disturbances. The disturbances seem to be connected
      with middle ear infections and with sensorineural hearing losses. Hearing loss in
      Ts women is not clinically apparent in most of the cases; this fact reflects the
      need of early evaluation and further monitoring of hearing organ in those
      patients. Sensorineural hearing loss seems to prevail in patients with 45,X
      genotype, so perhaps attention should be paid to this subgroup of Ts patients.

PMID- 18343511
TI  - Atrial fibrillation/flutter in myopathies.
AB  - With improved screening of patients with primary and secondary myopathies and
      more comprehensive investigations it turns out that an increasing number of
      patients with myopathies develops cardiac disease (cardiac involvement), before
      or after onset of the neuromuscular abnormalities. Cardiac involvement in
      myopathies manifests within the myocardium or the cardiac conduction system with
      impulse generation or conduction disturbances. An increasingly recognized rhythm
      abnormality in these patients is atrial fibrillation/flutter (AFI/AFL), which
      carries an increased risk for stroke embolism and represents an absolute
      indication for oral anticoagulation (OAC). Primary myopathies, in which AFI/AFL
      has been described so far include dystrophinopathies, Emery-Dreifuss muscular
      dystrophy, facio-scapulo-humeral muscular dystrophy, limb girdle muscular
      dystrophies, congenital myopathies, myofibrillar myopathies, myotonic
      dystrophies, glycogenoses, mitochondrial disorders, Barth syndrome, McLeod
      syndrome, and non-specific myopathies. Secondary myopathies, in which AFI/AFL has
      been described comprise polymyositis, dermatomyositis, colchicine-induced
      myopathy, and hyperthyroid myopathy. Myopathies most commonly associated with
      AFI/AFL are myotonic dystrophy and Emery-Dreifuss muscular dystrophy. Information
      about the frequency of stroke/embolism in these patients is rudimentary but there
      are indications that it is not increased in these patients. Only a few patients
      with AFI/AFL receive OAC to prevent from stroke/embolism. Patients with myopathy
      and AFI/AFL require thorough surveillance. If additional cardiovascular risk
      factors develop, OAC should be considered as in patients with other causes of
      AFI/AFL.

PMID- 18343512
TI  - Exploring the role of BRCA1, BRCA2 and RAD51 as biomarkers for breast cancer.

PMID- 18343513
TI  - Long-term results of stomach-conserving therapy in gastric MALT lymphoma.
AB  - PURPOSE: To evaluate long-term results of stomach-conserving therapy and to
      assess the value of histological probable minimal residual disease (pMRD) in
      predicting outcome in patients with gastric MALT lymphoma. MATERIALS AND METHODS:
      We studied 115 patients with stage I-II(2) gastric MALT lymphoma treated between
      1975 and 2002. Initially, first-line treatment consisted of radiotherapy only.
      Since 1994 most patients were primarily treated with Helicobacter pylori
      eradication; radiotherapy was used in case of eradication failure. To assess the
      value of pMRD, first follow-up biopsy samples classified as compete remission
      (CR) according to classical clinico-pathological criteria and biopsy samples 1
      year after assessment of histological CR were reviewed; results were related to
      outcome. RESULTS: Following radiotherapy only (n=56) 96% achieved a clinical CR;
      10-year cancer-specific survival rate was 94%. Following H. pylori eradication
      only (n=35) CR-rate was 43% and after additional treatment 89%; 5-year cause
      specific survival was 93%. There was no difference in relapse rate following
      initial histological CR or pMRD. CONCLUSIONS: Patients with early stage gastric
      MALT lymphoma have a favorable long-term outcome following conservative
      treatment. Outcome after H. pylori eradication followed by delayed radiotherapy
      on indication was excellent. In our series pMRD was not associated with increased
      risk of recurrence.

PMID- 18343514
TI  - Dosimetry quality audit of high energy photon beams in greek radiotherapy
      centers.
AB  - BACKGROUND AND PURPOSE: Dosimetry quality audits and intercomparisons in
      radiotherapy centers is a useful tool in order to enhance the confidence for an
      accurate therapy and to explore and dissolve discrepancies in dose delivery. This
      is the first national comprehensive study that has been carried out in Greece.
      During 2002--2006 the Greek Atomic Energy Commission performed a dosimetry
      quality audit of high energy external photon beams in all (23) Greek radiotherapy
      centers, where 31 linacs and 13 Co-60 teletherapy units were assessed in terms of
      their mechanical performance characteristics and relative and absolute dosimetry.
      MATERIALS AND METHODS: The quality audit in dosimetry of external photon beams
      took place by means of on-site visits, where certain parameters of the photon
      beams were measured, calculated and assessed according to a specific protocol and
      the IAEA TRS 398 dosimetry code of practice. In each radiotherapy unit (Linac or
      Co-60), certain functional parameters were measured and the results were compared
      to tolerance values and limits. Doses in water under reference and non reference
      conditions were measured and compared to the stated values. Also, the treatment
      planning systems (TPS) were evaluated with respect to irradiation time
      calculations. RESULTS: The results of the mechanical tests, dosimetry
      measurements and TPS evaluation have been presented in this work and discussed in
      detail. This study showed that Co-60 units had worse performance mechanical
      characteristics than linacs. 28% of all irradiation units (23% of linacs and 42%
      of Co-60 units) exceeded the acceptance limit at least in one mechanical
      parameter. Dosimetry accuracy was much worse in Co60 units than in linacs. 61% of
      the Co60 units exhibited deviations outside +/-3% and 31% outside +/-5%. The
      relevant percentages for the linacs were 24% and 7% respectively. The results
      were grouped for each hospital and the sources of errors (functional and human)
      have been investigated and discussed in details. CONCLUSION: This quality audit
      proved to be a useful tool for the improvement of quality in radiotherapy. It
      succeeded to disseminate the IAEA TRS-398 protocol in nearly all radiotherapy
      centers achieving homogenization and consistency of dosimetry within the country.
      Also, it detected discrepancies in dosimetry and provided guidance and
      recommendations to eliminate sources of errors. Finally, it proved that quality
      assurance programs, periodic quality control tests, maintenance and service play
      an important role for achieving accuracy and safe operation in radiotherapy.

PMID- 18343515
TI  - Intensity-modulated radiation therapy (IMRT) for inoperable non-small cell lung
      cancer: the Memorial Sloan-Kettering Cancer Center (MSKCC) experience.
AB  - INTRODUCTION: Intensity-modulated radiation therapy (IMRT) is an advanced
      treatment delivery technique that can improve the therapeutic dose ratio. Its use
      in the treatment of inoperable non-small cell lung cancer (NSCLC) has not been
      well studied. This report reviews our experience with IMRT for patients with
      inoperable NSCLC. METHODS AND MATERIALS: We performed a retrospective review of
      55 patients with stage I-IIIB inoperable NSCLC treated with IMRT at our
      institution between 2001 and 2005. The study endpoints were toxicity, local
      control, and overall survival. RESULTS: With a median follow-up of 26 months, the
      2-year local control and overall survival rates for stage I/II patients were 50%
      and 55%, respectively. For the stage III patients, 2-year local control and
      overall survival rates were 58% and 58%, respectively, with a median survival
      time of 25 months. Six patients (11%) experienced grade 3 acute pulmonary
      toxicity. There were no acute treatment-related deaths. Two patients (4%) had
      grade 3 or worse late treatment-related pulmonary toxicity. CONCLUSIONS: IMRT
      treatment resulted in promising outcomes for inoperable NSCLC patients.

PMID- 18343516
TI  - Face processing in adolescents with and without epilepsy.
AB  - Children with temporal lobe epilepsy frequently suffer memory deficits, often
      marked in face processing. To determine the neural correlates of this
      dysfunction, we investigated face processing in adolescents with intractable
      epilepsy compared to typically developing controls. The M170 and M220 MEG event
      related fields (ERFs) were recorded while the adolescents completed an n-back
      task on blocks of upright and inverted faces. Source analyses of the ERF data
      were performed using an event-related beamforming technique that allowed the
      detection of multiple sources. The control adolescents showed the expected
      waveforms and inversion effects, although there were differences in source
      localization, compared to the adult literature. The participants with epilepsy
      had poor performance on the tasks. The adolescents with extra-temporal lobe
      epilepsy showed both the M170 and M220 but the source localizations were highly
      atypical. The patients with right temporal lobe epilepsy had an absent or highly
      atypical M220, a component related to face recognition processes. We hypothesize
      that the children with extra-temporal lobe epilepsy have difficulty with face
      encoding processes while the patients with right temporal lobe epilepsy have
      specific difficulty with face recognition.

PMID- 18343517
TI  - Screening for motor coordination challenges in children using teacher ratings of
      physical ability and activity.
AB  - We examined the effectiveness of a teacher-based rating scale called the teacher
      estimation of activity form (TEAF) to screen for developmental coordination
      disorder (DCD) in children. A random selection of 15 of 75 schools from the
      District School Board of Niagara in Ontario, Canada was chosen for this study.
      Every consented child in Grade 4 (n=502) was evaluated for probable DCD (pDCD) in
      school using the short form Bruininks-Oseretsky test of motor proficiency (BOTMP
      SF). Each student also completed the children's self perceptions of adequacy in
      and predilection toward physical activity (CSAPPA) scale, participation
      questionnaire, and Leger 20-meter shuttle run, and had their height and weight
      measured. The 27 children (5.1%) who scored below the 5th percentile on BOTMP-SF
      were designated as pDCD cases and the 475 children who scored above the 5th
      percentile served as controls. Results showed that mean TEAF scores were
      significantly lower for pDCD children than controls (p<.001). Total TEAF scores
      ranging from 28 to 32 were preferred in maintaining good sensitivity (.74, 95%
      CI=.55-.87 to .85, 95% CI=.68-.94). The area under the ROC curve was .77 (95% CI,
      .68-.86) for the TEAF total score, and some individual items performed
      approximately as well as the full scale. The TEAF was positively correlated with
      measures of physical activity and fitness. The TEAF appears to be an effective
      tool in screening for DCD, particularly in a population setting. Considering the
      brevity of the TEAF and the discriminative power of individual items, this
      instrument would be effective in an abbreviated version.

PMID- 18343518
TI  - Behavioral and gene expression analyses of Wfs1 knockout mice as a possible
      animal model of mood disorder.
AB  - Wolfram disease is a rare genetic disorder frequently accompanying depression and
      psychosis. Non-symptomatic mutation carriers also have higher rates of depression
      and suicide. Because WfS1, the causative gene of Wolfram disease, is located at
      4p16, a linkage locus for bipolar disorder, mutations of WfS1 were suggested to
      be involved in the pathophysiology of bipolar disorder. In this study, we
      performed behavioral and gene expression analyses of Wfs1 knockout mice to assess
      the validity as an animal model of mood disorder. In addition, the distribution
      of Wfs1 protein was examined in mouse brain. Wfs1 knockout mice did not show
      abnormalities in circadian rhythm and periodic fluctuation of wheel-running
      activity. Behavioral analysis showed that Wfs1 knockout mice had retardation in
      emotionally triggered behavior, decreased social interaction, and altered
      behavioral despair depending on experimental conditions. Wfs1-like
      immunoreactivity in mouse brain showed a similar distribution pattern to that in
      rats, including several nuclei potentially relevant to the symptoms of mood
      disorders. Gene expression analysis showed down-regulation of Cdc42ep5 and Rnd1,
      both of which are related to Rho GTPase, which plays a role in dendrite
      development. These findings may be relevant to the mood disorder observed in
      patients with Wolfram disease.

PMID- 18343519
TI  - Neuroprotective effects of T-817MA against noise-induced hearing loss.
AB  - Oxidative stress, including reactive oxygen species and other free radicals, is
      thought to play an important role in neuronal cell death, including noise-induced
      hearing loss. 1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate
      (T-817MA), a novel neurotrophic agent, protects against oxidative stress-induced
      neurotoxicity. This study examines the effects of T-817MA in noise-induced
      ototoxicity in the cochlea. Guinea pigs received treatment with T-817MA-enhanced
      water (0.2, 0.7 mg/ml) or untreated water (control) beginning 10 days prior to
      noise exposure and continuing through this study. All subjects were exposed to 4
      kHz octave-band noise at 120-dB SPL for 5h. Auditory thresholds were assessed by
      sound-evoked auditory brainstem response at 4, 8, and 16kHz, prior to and 10 days
      following noise exposure. Hair cell damage was analyzed by quantitative
      histology. T-817MA significantly reduced threshold deficits and hair cell death.
      These results suggest T-817MA reduces noise-induced hearing loss and cochlear
      damage, suggesting functional and morphological protection.

PMID- 18343520
TI  - Low DNA HTLV-2 proviral load among women in Sao Paulo City.
AB  - BACKGROUND: HTLV-2 infections are almost always asymptomatic, and diseases
      associated with the infection are rarely reported. Little information is
      available on the relationship between HTLV-2 proviral load and gender or
      expression of disease, especially among patients with HIV-1 co-infection.
      METHODS: We studied 77 HTLV-2-infected subjects followed in our clinic for the
      last 9 years; 53 (69%) of them were co-infected with HIV-1. HTLV-2 DNA proviral
      load (PVL) was measured by real time PCR, a test with a sensitivity of 10 in
      10(4) PBMCs. RESULTS: Six of 53HTLV-2/HIV-1 cases had a myelopathy (all of them
      had undetectable PVL of HTLV-2). Only 3 of 35 women (2 out of 3 co-infected with
      HIV) had a detectable PVL, whereas 10 of 42 men had a detectable PVL. Regardless
      of their HIV status women had significantly lower PVL than men (10 vs. 43
      copies/10(4) PBMCs, p<0.05). CONCLUSIONS: We noticed the occurrence of myelopathy
      in HTLV-2/HIV-1 co-infected patients, with undetectable HTLV-2 viral load. There
      was a sex difference in viral load for HTLV-2, what may be the result in mode of
      transmission or acquisition of the virus.

PMID- 18343521
TI  - Injectable, thermo-reversible and complex coacervate combination gels for protein
      drug delivery.
AB  - Injectable and thermo-reversible physical combination gels were formed in aqueous
      solution by preparing complex coacervate with two oppositely charged
      biomacromolecules that composed of negatively charged chondroitin 6-sulfate and
      positively charged high molecular weight gelatin type A and co-formulating with a
      negative, thermo-sensitive polysaccharide, methylcellulose containing a salting
      out salt, ammonium sulfate. The combination of complex coacervation and a thermo
      reversible gel demonstrated synergistic effects on the complex coacervate
      formation the release rates of model proteins and in situ gel depot formation.
      Gels indicated sustained release patterns of the protein over 25 days with
      minimal initial bursts. Optimized novel in situ gel depot systems containing dual
      advantages of complex coacervation and temperature responsiveness demonstrated a
      potential for efficient protein drug delivery in terms of high protein loading,
      sustained protein release, ease of administration, an aqueous environment without
      toxic organic solvents, and a simple fabrication method.

PMID- 18343522
TI  - Overcoming the formulation obstacles towards targeted chemotherapy: in vitro and
      in vivo evaluation of cytotoxic drug loaded immunonanoparticles.
AB  - The aim of this study was to design a new one step conjugation of monoclonal
      antibodies (MAbs) to surface activated pegylated polyester nanoparticles (NPs)
      and evaluate the pharmacokinetic profile and therapeutic effect of paclitaxel
      palmitate (pcpl) loaded anti-HER2 immunoNPs in mice as compared to pcpl solution
      and NPs following IV injection. The density of the antibody conjugated to the NPs
      was found to be around 35 MAbs/NP (70% coupling efficiency). In vitro cell
      culture studies showed good binding and uptake results when immunoNPs were
      incubated with PC-3 and CAPAN-1 cell lines. Both pcpl NPs and immunoNPs showed
      significant increased t1/2, C(max) and AUC values as compared to the values of
      pcpl solution in mice. There was no significant difference in the C(max) and AUC
      values between pcpl NPs and pcpl immunoNPs. However, the immunoNPs concentrated
      much less in the liver and spleen than NPs. The pharmacokinetic behavior of the
      immunoNPs was markedly different from the pharmacokinetic profile of the naked
      MAb showing that the MAb lost its intrinsic molecular pharmacokinetic properties
      following conjugation to the NPs. The immunoNPs elicited a significant anti-tumor
      activity as compared to the pcpl solution and NPs, although the tumor growth was
      not fully inhibited.

PMID- 18343523
TI  - [Impact of physical activity on the autonomy and the quality of life of patients
      with spinal cord injury].
AB  - OBJECTIVE: To assess the effect of regular physical activity on the autonomy and
      the quality of life of Tunisian patients with spinal cord injury. METHODS: The
      study relates to 25 paraplegic divided into two groups: 10 paraplegic sportsmen
      and 15 sedentary paraplegics among whom we assess the degree of the autonomy with
      the Functional Independence Measure and the quality of life with the quality of
      life questionnaire SF36 in its Arabic version. RESULTS: The result analysis shows
      a significant difference of the total score of the Functional Independence
      Measure between the two groups, the sporting paraplegic having developed a better
      autonomy on the daily activities than the nonsporting paraplegics with a total
      average score of 115.10 against 93.87 (p<0.001). A significant difference is
      noted, mainly in the headings "personal care" and ',"mobility". Concerning the
      shutter "quality of life", the scores of various dimensions of scale SF36 were
      higher in the sporting paraplegic with significant difference in the headings
      bodily pain (p<0.01), vitality (p<0.04) and global physical score (p<0.008).
      CONCLUSION: This study enabled us to show that the regular physical activity as
      well had a positive effect on optimization of the functional capacities of
      paraplegic as on the improvement of its quality of life, thus, supporting a
      better socioprofessional reintegration.

PMID- 18343524
TI  - [A fatigue questionnaire (QFES) for child athletes: a four-year follow-up study
      in young skiers].

PMID- 18343525
TI  - Heparin-induced hyperkalemia.
AB  - An 85-year-old lady with type 2 diabetes mellitus of 32 years duration with
      peripheral neuropathy was admitted under the vascular surgeons with extensive
      gangrene of her lower limb. She was on insulin for the last 7 years. Initial
      investigations showed normal serum electrolytes. She was started on antibiotics
      and unfractionated heparin, and her electrolytes showed hyperkalemia, which
      persisted on active treatment. Her short synacthen test showed good response,
      renin was normal with low aldosterone, urinary pH, sodium, potassium and
      osmolality was normal. On stopping heparin serum, potassium became normal. On
      restarting heparin (low molecular weight) during a suspected episode of pulmonary
      embolism, she developed hyperkalemia and heparin was stopped. Her potassium and
      aldosterone became normal on discontinuation of heparin. She developed
      hyperkalemia with both unfractionated and low molecular weight heparin.

PMID- 18343526
TI  - Improving accuracy in astrocytomas grading by integrating a robust least squares
      mapping driven support vector machine classifier into a two level grade
      classification scheme.
AB  - Grading of astrocytomas is an important task for treatment planning; however, it
      suffers from significantly great inter-observer variability. Computer-assisted
      diagnosis systems have been propose to assist towards minimizing subjectivity,
      however, these systems present either moderate accuracy or utilize specialized
      staining protocols and grading systems that are difficult to apply in daily
      clinical practice. The present study proposes a robust mathematical formulation
      by integrating state-of-art technologies (support vector machines and least
      squares mapping) in a cascade classification scheme for separating low from high
      and grade III from grade IV astrocytic tumours. Results have indicated that low
      from high-grade tumours can be correctly separated with a certainty as high as
      97.3%, whereas grade III from grade IV tumours with 97.8%. The overall
      performance was 95.2%. These high rates have been a result of applying the least
      squares mapping technique to features prior to classification. A significant
      byproduct of least squares mapping is that the number of support vectors of the
      SVM classifiers dropped dramatically from about 80% when no mapping was used to
      less than 5% when mapping was used. The latter is a clear indication that the SVM
      classifier has a greater potential to generalize well to new data. In this way,
      digital image analysis systems for automated grading of astrocytomas are brought
      closer to clinical practice.

PMID- 18343527
TI  - Suspensions for intravenous (IV) injection: a review of development, preclinical
      and clinical aspects.
AB  - There has been growing interest in nanoparticles as an approach to formulate
      poorly soluble drugs. Besides enhanced dissolution rates, and thereby, improved
      bioavailability, nanoparticles can also provide targeting capabilities when
      injected intravenously. The latter property has led to increased research and
      development activities for intravenous suspensions. The first intravenously
      administered nanoparticulate product, Abraxane (a reformulation of paclitaxel),
      was approved by the FDA in 2006. Additional clinical trials have been conducted
      or are ongoing for multiple other indications such as oncology, infective
      diseases, and restenosis. This article reviews various challenges associated with
      developing intravenous nanosuspension dosage forms. In addition, various
      formulation considerations specific to intravenous nanosuspensions as well as
      reported findings from various clinical studies have been discussed.

PMID- 18343528
TI  - A review of thymic tumours.
AB  - Tumours of the thymus are uncommon and are generally regarded as being indolent.
      Whilst this is often true of thymomas; thymic adenocarcinoma and thymic
      neuroendocrine cancer can be aggressive and have a poor prognosis. Understanding
      the biology of these tumours is important for prognosis and management. The
      pathological features of these tumours are examined in detail. Imaging modalities
      for aiding in diagnosis and staging of these tumours are described; this includes
      CT and MRI, plus more recent advances including the use of FDG-PET and Indium-111
      Octreotide scintigraphy. The treatment options available including curative
      surgery, debulking surgery, chemotherapy, somatostatin analogues and peptide
      receptor radionuclide therapy are discussed. The optimal chemotherapy regimens
      are still unclear, although promising results have been obtained with platinum
      based chemotherapy. The role for adjuvant therapy in both thymic carcinoma and
      thymoma is unclear except, in patients with stage I thymomas. There is a high
      expression of somatostatin receptors in thymic tumours and anti-tumour benefit
      has been reported in patients treated with somatostatin analogues. A new
      development is the role of peptide receptor radionuclide therapy. This has become
      an established therapy in management of gastroenteropancreatic neuroendocrine
      tumours and its use has been recently described in case reports in both thymoma
      and thymic carcinoma.

PMID- 18343529
TI  - Simplified contaminant source depletion models as analogs of multiphase
      simulators.
AB  - Four simplified dense non-aqueous phase liquid (DNAPL) source depletion models
      recently introduced in the literature are evaluated for the prediction of long
      term effects of source depletion under natural gradient flow. These models are
      simple in form (a power function equation is an example) but are shown here to
      serve as mathematical analogs to complex multiphase flow and transport
      simulators. The spill and subsequent dissolution of DNAPLs was simulated in
      domains having different hydrologic characteristics (variance of the log
      conductivity field=0.2, 1 and 3) using the multiphase flow and transport
      simulator UTCHEM. The dissolution profiles were fitted using four analytical
      models: the equilibrium streamtube model (ESM), the advection dispersion model
      (ADM), the power law model (PLM) and the Damkohler number model (DaM). All four
      models, though very different in their conceptualization, include two basic
      parameters that describe the mean DNAPL mass and the joint variability in the
      velocity and DNAPL distributions. The variability parameter was observed to be
      strongly correlated with the variance of the log conductivity field in the ESM
      and ADM but weakly correlated in the PLM and DaM. The DaM also includes a third
      parameter that describes the effect of rate-limited dissolution, but here this
      parameter was held constant as the numerical simulations were found to be
      insensitive to local-scale mass transfer. All four models were able to emulate
      the characteristics of the dissolution profiles generated from the complex
      numerical simulator, but the one-parameter PLM fits were the poorest, especially
      for the low heterogeneity case.

PMID- 18343530
TI  - Adhesions ring: a structural comparison between podosomes and the immune synapse.
AB  - Podosomes and the immune synapse are integrin-mediated adhesive structures that
      share a common ring-like morphology. Both podosomes and immune synapses have a
      central core surrounded by a peripheral ring containing talin, vinculin and
      paxillin. Recent progress suggests significant parallels between the regulatory
      mechanisms that contribute to the formation of these adhesive structures. In this
      review, we compare the structures, functions and regulation of podosomes and the
      immune synapse.

PMID- 18343531
TI  - Identification by suppression subtractive hybridization of genes expressed in
      pear (Pyrus spp.) upon infestation with Cacopsylla pyri (Homoptera: Psyllidae).
AB  - The molecular interaction between pear tree (Pyrus spp.) and the phloem-feeding
      psylla Cacopsylla pyri (Linnaeus) was investigated through the construction and
      characterization of cDNA subtracted libraries. Genes expressed upon insect
      infestation were identified in the susceptible pear cultivar Bartlett and in the
      resistant selection NY10355. In both interactions, genes involved in the plant
      defense response were induced, confirming the observed similarity between the
      response to pathogens and to insects with piercing/sucking mouthparts. However,
      the two expression profiles were found to be different, with more genes involved
      in the response to biotic and abiotic stress being activated in the resistant
      plant than in the susceptible one. Further characterization of the identified
      genes could lead to the development of molecular markers associated with
      tolerance/resistance to pear psylla.

PMID- 18343532
TI  - Two cDNA clones (FsDhn1 and FsClo1) up-regulated by ABA are involved in drought
      responses in Fagus sylvatica L. seeds.
AB  - Two abscisic acid (ABA)-responsive clones (FsDhn1 and FsClo1) were isolated from
      a cDNA library of ABA-treated seeds of Fagus sylvatica L. FsDhn1 codes for type
      II late embryogenesis abundant (LEA) proteins, also known as dehydrins. The
      corresponding transcripts were ABA-induced and expressed when seeds were
      artificially dried. FsClo1 codes for a caleosin, a calcium-binding protein. By
      expressing FsCLO1 as a fusion protein in Escherichia coli, we obtained
      biochemical evidence of its ability to bind calcium, a second messenger involved
      in ABA signaling. This cDNA clone is seed specific, shows a LEA expression
      pattern and is also induced by ABA and dehydration treatments. The relationship
      of both genes with seed responses to ABA is discussed.

PMID- 18343533
TI  - Defining "natural product" between public health and business, 17th to 21st
      centuries.
AB  - The historical definition of a natural product stands at the crossroads of
      business, health, and the symbolic order of things. Until the end of the 19th
      century, "natural product" was a synonym of perishable. The emergency of organic
      chemistry made perishability be replaced with "toxicity". Nowadays, genetics is
      provoking a radical change in the notion and practises of "natural product".
      However, these concerns are never entirely opposed to "naturality" as a synonym
      for sacred and symbolic order. Traceability is largely based upon kosher
      practices and the association between organic and good for health is hardly based
      upon sound scientific arguments.

PMID- 18343534
TI  - Masculinity and food ideals of men who live alone.
AB  - Most studies of social aspects of foods have focused on people in multi-person
      households, often from the perspective of women. Little is known about the food
      related experiences of men who live alone. We therefore conducted a qualitative
      study with 12 men aged 27-47 who lived alone in Vancouver, Canada. Our goals were
      to explore their food-related ideals, and their perceptions of how those ideals
      relate to their actual food practices, the context of living alone, and masculine
      identities. Data were collected through food journals and semi-structured
      interviews. The men's ideals included being conscious and organized with respect
      to food so that they could regularly eat meals prepared at home from healthy
      ingredients. Eating with others was considered an ideal food context, where the
      meal became an "occasion", as opposed to "just eating". Participants believed
      that their eating habits often did not live up to these ideals because of lack of
      time and because the context of living alone was not conducive to eating well.
      However, they thought their habits were better than what they perceived to be the
      habits of a stereotypical bachelor who does not know how to cook and has a 'who
      cares' attitude towards food.

PMID- 18343535
TI  - Regulation of ghrelin structure and membrane binding by phosphorylation.
AB  - The peptide hormone ghrelin requires Ser-3 acylation for receptor binding,
      orexigenic and anti-inflammatory effects. Functions of desacylghrelin are less
      well understood. In vitro kinase assays reveal that the evolutionarily conserved
      Ser-18 in the basic C-terminus is an excellent substrate for protein kinase C.
      Circular dichroism reveals that desacylghrelin is approximately 12% helical in
      aqueous solution and approximately 50% helical in trifluoroethanol. Ser-18
      phosphorylation, Ser-18-Ala substitution, or Ser-3-acylation reduces the helical
      character in trifluoroethanol to approximately 24%. Both ghrelin and
      desacylghrelin bind to phosphatidylcholine:phosphatidylserine sucrose-loaded
      vesicles in a phosphatidylserine-dependent manner. Phosphoghrelin and
      phosphodesacylghrelin show greatly diminished phosphatidylserine-dependent
      binding. These results are consistent with binding of ghrelin and desacylghrelin
      to acidic lipids via the basic face of an amphipathic helix with Ser-18
      phosphorylation disrupting both helical character and membrane binding.

PMID- 18343536
TI  - Measles cases in highly vaccinated population of Novosibirsk, Russia, 2000-2005.
AB  - While the proportion of measles cases in vaccinees is expected to increase as
      vaccine coverage increases, such cases must be carefully investigated. The
      present study was conducted to examine possible contributions to vaccine failures
      (VFs) and to genetically characterize measles virus (MV) strains circulating in
      Novosibirsk, Russia during 2000-2005. Totally, 27 adult measles patients admitted
      to a regional hospital were prospectively enrolled in our study. Genetic
      characterization of the MV strains revealed circulation of genotypes A, D4 and D6
      between 2000 and 2003 years; a genotype D6 MV was associated with the 2005
      measles outbreak. Based on IgG avidity testing, half of the vaccinated patients
      demonstrated evidence of secondary vaccine failure (SVF). Patients, representing
      both levels of vaccine failure in our study were characterized by the lack of
      protective titers of neutralizing antibodies against circulating MVs, despite
      high IgG levels in many cases and high IgG avidity in SVF cases.

PMID- 18343537
TI  - The cost-effectiveness of a universal influenza vaccination program for adults
      aged 50-64 years in Australia.
AB  - Currently the Australian government funds universal influenza vaccine for all
      those aged > or =65 years under the National Immunisation Program (NIP). Annual
      vaccination rates in those aged 50-64 years are significantly lower than
      vaccination rates in those aged > or =65 years, and currently less than half
      those at high-risk of influenza-related complications aged 50-64 years are
      immunised. This study used a decision tree model to examine the cost
      effectiveness of lowering the age threshold for the influenza NIP in Australia to
      include those aged 50-64 years. From a healthcare payer perspective, a new
      influenza vaccination policy would cost $8908/QALY gained. From a societal
      perspective, a new influenza vaccination policy would cost $8338/QALY gained.
      From a governmental perspective, a new influenza vaccination policy would cost
      $22,408/QALY gained. The most influential parameters in deterministic sensitivity
      analysis included: probability of death due to influenza, vaccine efficacy
      against mortality, vaccine uptake, vaccine cost, and vaccine administration cost.
      Influenza vaccination for people aged 50-64 years appears highly cost-effective,
      and should be a strong candidate for funding under the NIP.

PMID- 18343538
TI  - Archaeosome adjuvants: immunological capabilities and mechanism(s) of action.
AB  - Archaeosomes (liposomes comprised of glycerolipids of Archaea) constitute potent
      adjuvants for the induction of Th1, Th2 and CD8(+) T cell responses to the
      entrapped soluble antigen. Archaeal lipids are uniquely constituted of ether
      linked isoprenoid phytanyl cores conferring stability to the membranes.
      Additionally, varied head groups displayed on the glycerol-lipid cores facilitate
      unique immunostimulating interactions with mammalian antigen-presenting cells
      (APCs). The polar lipid from the archaeon, Methanobrevibacter smithii has been
      well characterized for its adjuvant potential, and is abundant in archaetidyl
      serine, promoting interaction with a phosphatidylserine receptor on APCs. These
      archaeosomes mediate MHC class I cross-priming via the phagosome-to-cytosol TAP
      dependent classical processing pathway, and also upregulate costimulation by APCs
      without overt inflammatory cytokine production. Furthermore, they facilitate
      potent CD8(+) T cell memory to co-delivered antigen, comparable in magnitude and
      quality to live bacterial vaccine vectors. Archaeosome vaccines provide profound
      protection in murine models of infection and cancer. This technology is being
      developed for clinical application and offers a novel prospect for rational
      design and development of safe and potent subunit vaccines capable of eliciting T
      cell immunity against intracellular infections and cancers.

PMID- 18343539
TI  - High immunogenicity of a hydrophilic component of the hepatitis B virus preS1
      sequence exposed on the surface of three virus-like particle carriers.
AB  - The preS1phil, a hydrophilic component of the hepatitis B virus (HBV) preS1
      sequence, was exposed on the surface of three widely used virus-like particle
      (VLP) carriers by (i) insertion into the HI loop of the murine polyomavirus
      (MPyV) VP1, (ii) N-terminal addition to the hepatitis B surface (HBs) protein,
      and (iii) insertion into the major immunodominant region (MIR) of three hepatitis
      B core (HBc) vectors with different structure of their C-termini. Adjuvant-free
      immunisation of Balb/c mice demonstrated high preS1-specific antibody responses,
      but strong Th1 cell activation with efficient induction of IgG2a isotype
      antibodies was observed only in those VLPs, and namely in two of three HBc
      derivatives, which contained packaged RNA.

PMID- 18343540
TI  - Using immunization delivery strategies to accelerate progress in Africa towards
      achieving the Millennium Development Goals.
AB  - Integration of health services brings together common functions within and
      between organizations to solve common problems, developing a commitment to a
      shared vision and goals, and using common technologies and resources to achieve
      these goals. Integration has been the frustrated rally call of Primary Health
      Care for 30 years. This paper discusses the process of integrating child survival
      strategies and other heath services with immunization in Africa. Immunization is
      arguably the most successful health programme throughout the continent, making it
      the logical vehicle for add-on services. Strong health systems are the best way
      of delivering cost-effective child survival interventions in a most sustainable
      manner. But the reality in many African countries is that health systems have
      been weak for a number of reasons. Joining additional cost-effective child
      survival interventions on to immunization services may provide the needed boost.
      The unacceptably high childhood mortality in parts of Africa makes it the ideal
      location to undertake this exercise. The urgency to scale-up child survival
      interventions that have proven cost-effective is especially important if the
      Millennium Development Goals (MDGs) are to be met by 2015. Africa has more to
      loose than most in failing to scale up to meet these goals, bearing as it does
      the highest burden of childhood mortality in the world. But so far, prospects do
      not look good for achieving MDG-4 for the countries with the highest mortality
      rates. The timeliness of this initiative towards integration could not be better.
      In the last five years, countries in Africa have received massive injections of
      financial resources for polio eradication and measles control as well as
      additional funding for a range of immunization-strengthening activities and the
      introduction of new and under-utilized vaccines. While the data to support
      integration are limited, the information to hand suggests the effectiveness of
      the strategy. Where immunization performance is strong, immunization contacts may
      be excellent vehicles for additional interventions such as de-worming or
      Integrated Management of Childhood Illness (IMCI). But where an immunization
      service is struggling, adding another child survival intervention on to
      immunization might be the straw that breaks its back. Health managers have a wide
      range of options for adding on to immunization services, but the best choice will
      depend very much on local situations.

PMID- 18343542
TI  - The development and purpose of the FREDERICA radiation effects database.
AB  - Any system for assessing the impact of a contaminant on the environment requires
      an analysis of the possible effects on the organisms and ecosystems concerned. To
      facilitate this, the FREDERICA radiation effects database has been developed to
      provide an online search of the known effects of ionising radiation on non-human
      species, taken from papers in the scientific peer reviewed literature. The
      FREDERICA radiation effects database has been produced by merging the work done
      on radiation effects under two European funded projects (FASSET and EPIC) and
      making the database available online. This paper highlights applications for the
      database, gaps in the available data and explains the use of quality scores to
      help users of the database determine which papers may benefit their research in
      terms of techniques and reproducibility.

PMID- 18343541
TI  - Effectiveness of pneumococcal vaccination in older adults with chronic
      respiratory diseases: results of the EVAN-65 study.
AB  - A prospective cohort study evaluating the clinical effectiveness of the 23-valent
      pneumococcal polysaccharide vaccine was conducted among 1298 Spanish older adults
      with chronic respiratory diseases (bronchitis, emphysema or asthma) who were
      followed between 2002 and 2005. Main outcomes were all-cause community-acquired
      pneumonia (CAP) and 30 days mortality from CAP. The association between
      vaccination and the risk of each outcome was evaluated by multivariable Cox
      proportional-hazard models adjusted for age and comorbidity pneumococcal
      vaccination did not alter significantly the risk of overall CAP (hazard ratio
      [HR]: 0.77; 95% confidence interval [CI]: 0.56-1.07) and 30 days mortality from
      CAP (HR: 0.87; 95% CI: 0.33-2.28). However, a borderline significant reduction of
      30% in the risk of all-cause hospitalisation for CAP was observed among
      vaccinated subjects (HR: 0.70; 95% CI: 0.48-1.00; p=0.052). The effectiveness of
      the vaccine on the combined endpoint of pneumococcal and unknown organism
      infections reached 34% (HR: 0.66; 95% CI: 0.43-1.01; p=0.059). Although our
      findings suggest moderate benefits from the vaccination, the evidence of clinical
      effectiveness appears limited.

PMID- 18343543
TI  - Transfer of radionuclides in aquatic ecosystems--default concentration ratios for
      aquatic biota in the Erica Tool.
AB  - The process of assessing risk to the environment following a given release of
      radioactivity requires the quantification of activity concentrations in
      environmental media and reference organisms. The methodology adopted by the ERICA
      Integrated Approach involves the application of concentration ratios (CR values)
      and distribution coefficients (K(d) values) for aquatic systems. Within this
      paper the methodologies applied to derive default transfer parameters, collated
      within the ERICA Tool databases, are described to provide transparency and
      traceability in the documentation process. Detailed information is provided for
      the CR values used for marine and freshwater systems. Of the total 372 CR values
      derived for the marine ecosystem, 195 were identified by literature review. For
      the freshwater system, the number of values based on review was less, but still
      constituted 129 from a total of 372 values. In both types of aquatic systems, 70
      80% of the data gaps have been filled by employing "preferable" approaches such
      as those based on substituting values from taxonomically similar organisms or
      biogeochemically similar elements.

PMID- 18343544
TI  - Sialosis: 35 cases of persistent parotid swelling from two countries.
AB  - Diffuse, non-inflammatory, non-neoplastic enlargement of the major salivary
      glands (sialosis) is uncommon and has various systemic causes. This paper
      examines 35 patients whose persistent swelling of the parotid was diagnosed as
      sialosis, and shows that diabetes mellitus and alcoholism are the most common
      causes.

PMID- 18343545
TI  - Use of bioreactors in maxillofacial tissue engineering.
AB  - Engineering of various oral tissues is a challenging issue in contemporary
      maxillofacial reconstructive research. In contrast to the classic biomaterial
      approach, tissue engineering is based on the understanding of cell driven tissue
      formation, and aims to generate new functional tissues, rather than just to
      implant non-living space holders. Researchers hope to reach this goal by
      combining knowledge from biology, physics, materials science, engineering, and
      medicine in an integrated manner. Several major technical advances have been made
      in this field during the last decade, and clinical application is at the stage of
      first clinical trials. A recent limitation of extracorporally engineered cellular
      substitutes is the problem of growing enlarged tissues ex vivo. One of the main
      research topics is therefore to scale up artificial tissue constructs for use in
      extended defect situations. To overcome the monolayer inherent two-dimensional
      cell assembly, efforts have been made to grow cells in a three-dimensional space.
      Bioreactors have therefore been in focus for a considerable time to build up
      enlarged tissues. The shift from the ex vivo approach of cell multiplication to
      the generation of a real tissue growth is mirrored by the development of
      bioreactors, enabling scientists to grow more complex tissue constructs. This
      present review intends to provide an overview of the current state of art in
      maxillofacial tissue engineering by the use of bioreactors, its limitations and
      hopes, as well as the future research trends.

PMID- 18343546
TI  - Giant neglected ameloblastoma: single stage treatment and clinicopathological
      review.
AB  - Giant ameloblastomas may present with massive swelling of the jaws. We report a
      giant ameloblastoma of the mandible in a Nigerian patient that measured
      15.1x12.2x13.6cm and was managed with a single procedure. The tumour was removed
      by segmental mandibulectomy and reconstructed with a fibular free flap. The
      excess soft tissue was treated with a bilateral commissuroplasty. Single stage
      treatment that establishes early functional and aesthetic recovery offers
      advantages over multi staged procedures, and is therefore the treatment of choice
      for giant ameloblastomas.

PMID- 18343547
TI  - Phthalate esters (PAEs): emerging organic contaminants in agricultural soils in
      peri-urban areas around Guangzhou, China.
AB  - This study reports the first data on the concentrations and distribution of
      phthalate esters (PAEs) in the agricultural soils from the peri-urban areas of
      Guangzhou city. Sigma(16)PAEs concentrations ranged from 0.195 to 33.6 microg g(
      1)-dry weight (dw). Elevated levels of PAEs were recorded in the vegetable fields
      located next to the urban districts, and a decreasing trend exists following the
      distance away from the urban center. Diisobutyl phthalate (DiBP), Di-n-butyl
      phthalate (DnBP), and Di(2-ethylhexyl) phthalate (DEHP) dominated the PAEs in the
      agricultural soils. Significant relationship (correlation coefficient R(2)=0.85,
      p<0.01, n=40) was present between the accumulation of PAEs and total organic
      carbons in agricultural soils. In addition, both pH and texture of soils are
      found to be important factors affecting the level of PAEs. This study shows that
      the agricultural soils in the peri-urban area of Guangzhou city were moderately
      polluted by PAEs.

PMID- 18343548
TI  - Social learning modulates the lateralization of emotional valence.
AB  - Although neuropsychological studies of lateralization of emotion have emphasized
      valence (positive vs. negative) or type (basic vs. complex) dimensions, the
      interaction between the two dimensions has yet to be elucidated. The purpose of
      the current study was to test the hypothesis that recognition of basic emotions
      is processed preferentially by the right prefrontal cortex (PFC), whereas
      recognition of complex social emotions is processed preferentially by the left
      PFC. Experiment 1 assessed the ability of healthy controls and patients with
      right and left PFC lesions to recognize basic and complex emotions. Experiment 2
      modeled the patient's data of Experiment 1 on healthy participants under
      lateralized displays of the emotional stimuli. Both experiments support the Type
      as well as the Valence Hypotheses. However, our findings indicate that the
      Valence Hypothesis holds for basic but less so for complex emotions. It is
      suggested that, since social learning overrules the basic preference of valence
      in the hemispheres, the processing of complex emotions in the hemispheres is less
      affected by valence.

PMID- 18343549
TI  - Mirtazapine precipitated seizures: a case report.

PMID- 18343550
TI  - Poor agreement amongst psychiatrists assessing rationality in five cases of
      psychiatric polypharmacy.

PMID- 18343551
TI  - Memantine decreases hippocampal glutamate levels: a magnetic resonance
      spectroscopy study.
AB  - Glutamate (Glu) is associated with excitotoxic cell damage. Memantine modulates
      the glutamate induced excitotoxicity in Alzheimer's disease (AD). No information
      is available as to the influence of memantine on in vivo brain glutamate levels.
      Hippocampal Glu levels were measured in cognitively impaired and normal
      individuals (n=10) before and after 6 months of memantine treatment, using three
      dimensional high spatial resolution (0.5 cm(3) voxels) proton magnetic resonance
      spectroscopy at 3 T. These measurements were also repeated in a non-treated
      cognitively normal group (n=6). Treatment with memantine decreased Glu/Cr
      (creatine) ratio in the left hippocampal region. Memantine reduced hippocampal
      glutamate levels, which may be consistent with its anti-excitotoxic property.

PMID- 18343552
TI  - Cycling mood disturbances and progressive neurological symptoms in a patient with
      Huntington's disease.

PMID- 18343553
TI  - Chemopreventive effects of a serratane-type triterpenoid, 3alpha-methoxyserrat-14
      en-21beta-ol (PJ-1), against rat lung carcinogenesis.
AB  - Our efforts to search for cancer-chemopreventive agents have been focused on
      constituents from materials of trees such as leaves and bark as waste in the
      forestry industry. Cancer-chemopreventive effects of a serratane-type
      triterpenoid from the bark of Picea jezoensis, 3alpha-methoxyserrat-14-en-21beta
      ol (PJ-1), were here examined in a revised rat multi-organ carcinogenesis (DMBDD)
      model. Male 6-week-old F344 rats received combined treatment with five different
      carcinogens and starting 1 week thereafter were administered PJ-1 at a dose of
      2mg/kg or 6mg/kg body wt i.g. (five times/week) or the vehicle as a control (1ml
      of 0.5% CMC). At the termination at week 30, significant decrease of adenomas
      (P<0.01) and total tumors (P<0.01) and a trend for reduction of adenocarcinoma
      multiplicity in the lung were observed, but without any modulating influence in
      other major organs. The cell proliferation indices in the lungs tended to be
      decreased in the PJ-1 administered groups, with apparent induction of CYP2B1/2
      mRNA expression to recover the values observed in non-initiated controls. These
      results indicate that PJ-1 exerts cancer-chemopreventive effects on rat lung
      carcinogenesis after multi-organ initiation.

PMID- 18343554
TI  - Comparison of the skin sensitizing potential of unsaturated compounds as assessed
      by the murine local lymph node assay (LLNA) and the guinea pig maximization test
      (GPMT).
AB  - The skin sensitization potential of eight unsaturated and one saturated lipid
      (bio)chemicals was tested in both the LLNA and the GPMT to address the hypothesis
      that chemicals with unsaturated carbon-carbon double bonds may result in a higher
      number of unspecific (false positive) results in the LLNA compared to the GPMT.
      Seven substances (oleic acid, linoleic acid, linolenic acid, undecylenic acid,
      maleic acid, squalene and octinol) gave clear positive results in the LLNA
      (stimulation index (SI)> or = 3) and thus would require labelling as skin
      sensitizer. Fumaric acid and succinic acid gave clearly negative results. In the
      GPMT, besides some sporadic skin reactions, reproducible skin reactions
      indicating an allergic response were found in a few animals for four test
      substances. Based on the GPMT results, only undecylenic acid would have to be
      classified and labelled as a skin sensitizer according to the European Dangerous
      Substance Directive (67/548/EEC) (results for linoleic acid were inconclusive),
      while the other seven test substances would not require labelling. Possible
      mechanisms for unspecific skin cell stimulation and lymph node responses are
      discussed. In conclusion, the suitability of the LLNA for unsaturated compounds
      bearing structural similarity to the tested substances should be carefully
      considered and the GPMT should remain available as an accepted test method for
      skin sensitization hazard identification.

PMID- 18343555
TI  - Corneal tattoo with tea infusion.
AB  - Except in animal models of cataractogenesis, the literature on the effects of tea
      infusion on ocular tissue is scant. In our patient, prolonged exposure to tea
      infusion may have led to a hypesthetic cornea with secondary limbal stem cell
      loss. In turn, the eye developed keratinization and corneal neovascularization.

PMID- 18343556
TI  - l-Cysteine and glutathione restore the modulation of rat frontal cortex Na+, K+ 
      ATPase activity induced by aspartame metabolites.
AB  - BACKGROUND: Studies have suggested that aspartame (ASP) ingestion is implicated
      in neurological problems. AIM: The aim of this study was to evaluate rat frontal
      cortex Na+, K+ -ATPase and Mg2+ -ATPase activities after incubation with ASP or
      each of its metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid
      (asp) separately. METHOD: Suckling rat frontal cortex homogenates or pure Na+, K+
      -ATPase were incubated with ASP metabolites. Na+, K+ -ATPase and Mg2+ -ATPase
      activities were measured spectrophotometrically. RESULTS: Incubation of frontal
      cortex homogenate or pure Na+, K+ -ATPase with various ASP concentrations as
      expected in the cerebrospinal fluid (CSF) after ASP consumption of 34, 150 or
      200mg/kg, decreased the frontal cortex enzyme activity by 33%, 53% or 57%,
      respectively, whereas pure enzyme was remarkably stimulated. Moreover, incubation
      of frontal cortex homogenate with each one of the expected ASP metabolites in the
      CSF, except MeOH, which are related to the intake of the above mentioned doses of
      the sweetener, resulted in an activation of the membrane Na+, K+ -ATPase, as well
      as pure enzyme. Frontal cortex Mg2+-ATPase remained unaltered. Addition of l
      cysteine (cys) or reduced glutathione (GSH) to ASP metabolites mixtures,
      corresponding to 150 or 200mg/kg doses of the sweetener, completely or partially
      restored to normal the modulated membrane and pure Na+, K+ -ATPase activities.
      CONCLUSION: CSF concentrations of the sum of ASP metabolites corresponding to the
      intake of common, abuse or toxic doses (34 or 150 or 200mg/kg, respectively) of
      the additive significantly increased rat frontal cortex Na+, K+ -ATPase and pure
      enzyme activities. Cys or GSH completely or partially restored to normal both
      enzyme activities, possibly due to amelioration of the cellular GSH reduction
      from the action of MeOH, a metabolite of the sweetener and/or by their scavenging
      effect.

PMID- 18343557
TI  - Lack of compliance with basic infection control measures during cardiopulmonary
      resuscitation--are we ready for another epidemic?
AB  - OBJECTIVE: Healthcare workers in the emergency department are particularly
      vulnerable to communicable disease. This study aimed to evaluate compliance with
      standard precautions by analysis of the incidence and systems sources of such
      contaminations and by quantifying the use of personal protective equipment.
      METHOD: A prospective observational study from 1 November 2005 to 30 April 2006,
      using analysis of video segments. Videotapes were recorded in two rooms designed
      for cardiopulmonary resuscitation of out-of-hospital cardiac arrests, and
      compliance with basic infection control measures by all emergency department
      crews was monitored. RESULTS: A total of 44 consecutive performances of
      cardiopulmonary resuscitation were recorded for time-motion analysis. The
      percentages of staff wearing personal protective equipment were 90%, 50%, 20% and
      75% for masks, eye protection, gowns and gloves, respectively. Compliance ranking
      scored doctors as high, trainees as moderate and nursing staff as low. Overall
      contamination rate was 16.9x10(-2) events/person-min. The two leading systems
      sources for contamination were lack of specific task assignments among rescuers
      (44%) and inadequate preparation for procedures (42%). CONCLUSIONS: Among
      healthcare workers in the emergency setting, the study disclosed suboptimal
      compliance with basic infection control measures, including use of personal
      protective equipment and avoiding contamination. By further time-motion analysis
      of resuscitation sessions, major systems sources and strategies for improvement
      could be identified.

PMID- 18343558
TI  - Developmental aspects of automatic word processing: language lateralization of
      early ERP components in children, young adults and middle-aged subjects.
AB  - Reading words elicits a very early evoked potential termed "recognition
      potential" with a latency of about 150 ms and clearly located in left posterior
      regions. A review of the current literature indicates that N150 marks the
      automatic lexical classification of a word, is relatively independent of the
      task, and is followed by a later negative and more anterior component which is
      sensitive to the task. However, from the literature it is not clear whether the
      left lateralization of the neural networks involved in word recognition changes
      with age and experience, and how this lateralization is related with behavioral
      performance. To this aim, based on a previously validated paradigm [Spironelli,
      C., Angrilli, A., 2006. Language lateralization in Phonological, Semantic and
      Orthographic tasks: a slow evoked potential study. Behavioral Brain Research 175,
      296-304; Spironelli, C., Angrilli, A., 2007. Influence of Phonological, Semantic
      and Orthographic tasks on the early linguistic components N150 and N350.
      International Journal of Psychophysiology 64, 190-198], we ran an experiment on
      three samples of subjects, 28 children (mean: 10 years), 22 young adults (23
      years) and 20 middle-aged subjects (59 years). Subjects had to read the same
      sample of words in three blocked tasks, Orthographic, Phonological and Semantic,
      while EEG was recorded from 38 scalp locations. Analysis performed on N150 and
      four regions of interest/quadrants revealed typical significant left posterior
      negativity in young and aged subjects, but reversed lateralization and greater
      right negativity in children compared with the two adult groups. Analysis of the
      later N350 revealed a significant three-way group x laterality x task
      interaction, showing greater left negativity on the Phonological task only in the
      two adult groups, and a bilateral component in children. Results indicate that
      the functional lateralization of linguistic neural networks involved in automatic
      word recognition and in phonological processing is not yet developed in
      linguistically competent children aged 10 years, whereas the observed
      lateralization is relatively stable and not degraded in moderately aged subjects.
      Results are discussed in view of their implications for age-related linguistic
      pathologies.

PMID- 18343559
TI  - The scope for regulatory incentives to encourage increased efficiency of input
      use by farmers.
AB  - Managing diffuse water pollution from agricultural land continues to be one of
      the more intractable challenges for environmental policy. The advent of the Water
      Framework Directive places the onus on EU member states to identify reasons why
      water bodies fail or are at risk of failure to meet good ecological status. In
      such cases, programmes of measures are to be enacted to mitigate the causes at
      least cost. Failing this, users may ultimately be faced with the full costs of
      pollution. This paper considers the scope for measures that address nitrogen and
      phosphorus pollution at source. Specifically the paper relates the diffuse
      pollution problem to the extent of over application of nitrogen and phosphorus.
      Data envelopment analysis applied to English cereal and dairy farmers, provides
      an indication of resource use and evidence of over application. This inefficiency
      provides a potential basis for either a least cost abatement approach using
      effective information and advice, or alternatively a pollution charge.

PMID- 18343560
TI  - Global monitoring of wetlands--the value of ENVISAT ASAR Global mode.
AB  - This paper elaborates on recent advances in the use of ScanSAR technologies for
      wetland-related research. Applications of active satellite radar systems include
      the monitoring of inundation dynamics as well as time series analyses of surface
      soil wetness. For management purposes many wetlands, especially those in dry
      regions, need to be monitored for short and long-term changes. Another
      application of these technologies is monitoring the impact of climate change in
      permafrost transition zones where peatlands form one of the major land cover
      types. Therefore, examples from boreal and subtropical environments are presented
      using the analysed ENVISAT ASAR Global mode (GM, 1 km resolution) data acquired
      in 2005 and 2006. In the case of the ENVISAT ASAR instrument, data availability
      of the rather coarse Global Mode depends on request priorities of other competing
      modes, but acquisition frequency may still be on average fortnightly to monthly
      depending on latitude. Peatland types covering varying permafrost regimes of the
      West Siberian Lowlands can be distinguished from each other and other land cover
      by multi-temporal analyses. Up to 75% of oligotrophic bogs can be identified in
      the seasonal permafrost zone in both years. The high seasonal and inter-annual
      dynamics of the subtropic Okavango Delta can also be captured by GM time series.
      Response to increased precipitation in 2006 differs from flood propagation
      patterns. In addition, relative soil moisture maps may provide a valuable data
      source in order to account for external hydrological factors of such complex
      wetland ecosystems.

PMID- 18343561
TI  - Editorial comment on: histological changes in the urothelium and suburothelium of
      human overactive bladder following intradetrusor injections of botulinum
      neurotoxin type A for the treatment of neurogenic or idiopathic detrusor
      overactivity.

PMID- 18343562
TI  - Management of the hormone sensitivity of prostate cancer: where are we now?

PMID- 18343563
TI  - Editorial comment on: Lower plasma adiponectin levels are associated with larger
      tumor size and metastasis in clear-cell carcinoma of the kidney.

PMID- 18343564
TI  - Histological changes in the urothelium and suburothelium of human overactive
      bladder following intradetrusor injections of botulinum neurotoxin type A for the
      treatment of neurogenic or idiopathic detrusor overactivity.
AB  - BACKGROUND: We examined, for the first time in a prospective study, the
      histological changes in the urothelium and suburothelium of patients with
      neurogenic (NDO) or idiopathic detrusor overactivity (IDO) after one or repeat
      treatments with intradetrusor BoNTA. METHODS: Flexible cystoscopic bladder
      biopsies were obtained from patients with urodynamically proven intractable
      spinal NDO or IDO before and 4 and 16 wk after one or repeat treatments with
      intradetrusor injections of BOTOX1 (NDO 300 U, IDO 200 U). Specimens were stained
      for haematoxylin-eosin and analysed blindly for inflammatory changes, fibrosis,
      hyperplasia, and dysplasia in the urothelium and suburothelium. Statistical
      comparisons were significant at p values less than 0.05. RESULTS: Signs of
      chronic inflammation were found in 59.1% of baseline biopsies (65.6% of NDO vs.
      50% of IDO, p=0.049), 67.6% of post-first biopsies and 86.4% after repeat
      injections. The two groups were comparable for degree of baseline inflammation,
      which did not change significantly after first injection and up to 16 wk after a
      third injection. Mild fibrosis was found in 2.2% of biopsies examined, equally
      before and after treatment, but not after repeat injections. No dysplasia or
      hyperplasia was identified. Eosinophils were identified more frequently in
      biopsies taken after repeat injections compared with the post-first injection and
      baseline biopsies (chi2=8.23, p=0.018). No difference existed between NDO and IDO
      bladders. CONCLUSIONS: BoNTA injections do not appear to be producing significant
      inflammatory changes, fibrosis, or dysplastic changes in human bladder
      urothelium/suburothelium after a single injection and in a limited number of
      repeat treatment biopsies. The presence of eosinophils might be treatment
      related, because they were mostly found in post-treatment biopsies.

PMID- 18343565
TI  - Lower plasma adiponectin levels are associated with larger tumor size and
      metastasis in clear-cell carcinoma of the kidney.
AB  - OBJECTIVES: To examine a possible relationship between plasma adiponectin levels
      and renal cell carcinoma (RCC). Adiponectin, a cytokine secreted by adipocytes,
      is a potent antiangiogenic factor. Plasma levels of adiponectin in patients with
      RCC and tumor adiponectin receptors R1 and R2 (AdipoR1&2) expression levels were
      measured and correlated with disease characteristics. METHODS: Preoperative
      plasma samples from 42 patients were analyzed in triplicate for adiponectin
      levels with a specific ELISA assay. All patients had clear-cell RCC, including 15
      with metastatic disease. Diabetic patients were excluded; all had normal renal
      function. The RCC and surrounding normal renal tissue were comparatively analyzed
      for AdipoR1&2 expressions (immunoblotting) in 15 patients. RESULTS: Mean, median,
      and range of plasma adiponectin levels were 6.33, 5.84, and 1-25.2 microg/ml,
      respectively. A strong inverse correlation was found between plasma adiponectin
      levels and tumor size with significantly lower levels of adiponectin in tumors >
      or =4 cm (p<0.01). The median adiponectin levels in metastatic and nonmetastatic
      patients were 4.08 and 7.4 microg/ml, respectively (p=0.029). A trend toward
      significant lower adiponectin levels in high versus low Fuhrman grade (3 and 4
      vs. 1 and 2) was noted (p=0.057). Expression of AdipoR1&R2 was found to be lower
      in tumor tissue compared with the patient's normal surrounding kidney tissues in
      40% of the cases. Metastatic tumors expressed lower levels of AdipoR2. Body mass
      index was not inversely correlated with adiponectin levels. CONCLUSIONS: Lower
      blood levels of adiponectin are positively associated with clear-cell RCC
      aggressiveness and could potentially be used as a biomarker.

PMID- 18343566
TI  - Dysregulation of peripheral endocannabinoid levels in hyperglycemia and obesity:
      Effect of high fat diets.
AB  - Increasing evidence indicates that endocannabinoid (EC) signalling is
      dysregulated during hyperglycemia and obesity, particularly at the level of
      anandamide (AEA) and/or 2-arachidonoylglycerol (2-AG) concentrations in tissues
      involved in the control of energy intake and processing, such as the liver, white
      adipose tissue and pancreas. Here we review this previous evidence and provide
      new data on the possible dysregulation of EC levels in organs with endocrine
      function (adrenal glands and thyroid), involved in energy expenditure (brown
      adipose tissue and skeletal muscle), or affected by the consequences of metabolic
      disorders (heart and kidney), obtained from mice fed for 3, 8 and 14 weeks with
      two different high fat diets (HFDs), with different fatty acid compositions and
      impact on fasting glucose levels. Statistically significant elevations (in the
      skeletal muscle, heart and kidney) or reductions (in the thyroid) of the levels
      of either AEA or 2-AG, or both, were found. Depending on the diet, these changes
      preceded or accompanied the development of overt obesity and/or hyperglycemia. In
      the adrenal gland, first a reduction and then an elevation of EC levels were
      observed. In the brown fat, a very early elevation of both AEA and 2-AG
      normalized levels was observed with one of the diets, whereas delayed decreases
      were explained by an increase of the amount of fat tissue weight induced by the
      HFDs. The potential implications of these and previous findings in the general
      framework of the proposed roles of the EC system in the control of metabolic,
      endocrine and cardiovascular and renal functions are discussed.

PMID- 18343567
TI  - Novel modes of oestrogen receptor agonism and antagonism by hydroxylated and
      chlorinated biphenyls, revealed by conformation-specific peptide recognition
      patterns.
AB  - Because of the concern about environmental chemicals with oestrogenic and anti
      oestrogenic effects, there is a need to construct biosensors for classifying such
      chemicals according to their effect on oestrogen receptor conformation. The
      conformation of the ligand-binding domains (LBD) of oestrogen receptor-alpha and 
      beta determine their transcription regulation activity. Some ligands, i.e., the
      natural oestrogen oestradiol, induce an active conformation allowing interaction
      with co-activators. In contrast, antagonists like ICI 182, 780, because of their
      bulky side chains, do not allow an alpha-helix 12 positioning compatible with co
      activator binding. Another type of oestrogen receptor-ligand interactions, termed
      "passive antagonism", was first defined by X-ray crystal structure analysis of
      receptors in complex with the side chain-less 5,11-cis-diethyl-5,6,11,12
      tetrahydrochrysene-2,8-diol (THC). We have now used the ability of peptides
      selected from phage-displayed peptide libraries to bind conformation specifically
      to oestrogen receptor-alpha and -beta LBDs to analyse conformations induced by
      THC and a group of chlorinated biphenyls and their aryl-hydroxylated metabolites,
      suspected of being environmental chemical disruptors. In oestrogen receptor-beta,
      THC defined a "passive antagonist" peptide recognition pattern, which was also
      induced by several antagonistic hydroxylated biphenyls, while a clearly different
      peptide recognition pattern was induced by their chlorinated agonistic
      counterparts. In oestrogen receptor-alpha, THC induced a conformation similar to
      that induced by oestriol and other oestrogen receptor-alpha agonists, which, as
      evaluated by site-directed mutagenesis, have a functionally important interaction
      with oestrogen receptor-alpha residue His524. We conclude that the peptide
      recognition pattern can be used to classify suspected environmental endocrine
      disruptors according the oestrogen receptor-alpha and -beta conformations they
      induce.

PMID- 18343568
TI  - Narcolepsy presenting as REM sleep behaviour disorder.
AB  - REM sleep behaviour disorder (RBD) is a neurological condition well known to be
      associated with the synucleinopathies in middle-aged patients. However, there is
      much less data concerning its development, evolution, and association with other
      disorders in younger patients. We report two patients aged less than 33 years who
      presented with clinical and polysomnographical features of RBD, both of whom
      proved to have previously undiagnosed narcolepsy. Whilst the association of
      narcolepsy with RBD has been previously recognised, this is the first report of
      narcoleptic patients presenting with RBD. Narcolepsy should be included in the
      differential diagnosis of young patients presenting with abnormal behaviour
      during sleep compatible with RBD.

PMID- 18343569
TI  - Indirubin-3'-monoxime, a derivative of a Chinese anti-leukemia medicine, inhibits
      Notch1 signaling.
AB  - Notch proteins perform a critical function in cell-fate decisions and in
      differentiation. In this study, we determined that indirubin-3'-monoxime reduced
      Notch1 signaling to a remarkable extent. Indirubin-3'-monoxime has been shown to
      inhibit both constitutive active mutants of Notch1 and Notch1-IC-mediated
      transactivation activity. However, in such cases, neither the Notch cleavage
      pattern nor the protein stability of Notch1-IC was determined to have been
      significantly altered. Indirubin-3'-monoxime suppresses Notch1 transcriptional
      activity via the dissociation of the Notch1-IC-RBP-Jk complex. Notably, the
      transcriptional activity of Notch1-IC was not suppressed significantly in the GSK
      3beta null cells by indirubin-3'-monoxime as compared to what was observed with
      GSK-3beta wild-type cells. In the previous study, we synthesized a series of
      indirubin derivatives. Interestingly, some of these indirubin derivatives were
      characterized as potent inhibitors of Notch1 signaling. Taken together, the
      results of this study indicate that indirubin-3'-monoxime downregulated Notch1
      signaling in a GSK-3beta-dependent and proteosomal degradation-independent
      manner.

PMID- 18343570
TI  - A risk-based sensor placement methodology.
AB  - A risk-based sensor placement methodology is proposed to solve the problem of
      optimal location of sensors to protect population against the exposure to, and
      effects of, known and/or postulated chemical, biological, and/or radiological
      threats. Risk is calculated as a quantitative value representing population at
      risk from exposure at standard exposure levels. Historical meteorological data
      are used to characterize weather conditions as the frequency of wind speed and
      direction pairs. The meteorological data drive atmospheric transport and
      dispersion modeling of the threats, the results of which are used to calculate
      risk values. Sensor locations are determined via an iterative dynamic programming
      algorithm whereby threats detected by sensors placed in prior iterations are
      removed from consideration in subsequent iterations. In addition to the risk
      based placement algorithm, the proposed methodology provides a quantification of
      the marginal utility of each additional sensor. This is the fraction of the total
      risk accounted for by placement of the sensor. Thus, the criteria for halting the
      iterative process can be the number of sensors available, a threshold marginal
      utility value, and/or a minimum cumulative utility achieved with all sensors.

PMID- 18343571
TI  - Preparation of mesoporous titania solid superacid and its catalytic property.
AB  - Mesoporous titania (TiO(2)) was synthesized by hydrothermal method using
      cetyltrimethyl ammonium bromide (CTAB) as a template and using anhydrous ethanol
      and tetra-n-butyl titanate (TBOT) as raw materials. Mesoporous titania solid
      superacid and nanosized titania solid superacid catalysts were prepared by wet
      impregnation method. The structure and property of as-prepared samples were
      characterized by means of XRD, FT-IR and N(2) physical adsorption. The
      esterification of salicylic acid with isoamyl alcohol and the condensation of
      cyclohexanone with ethylene were used as model reactions to test the catalytic
      activities of the catalysts. On the other hand, the comparison of catalytic
      activities of the prepared solid superacid catalysts and the conventional liquid
      acid H(2)SO(4) was also carried out under the same experimental conditions. The
      results show that the catalytic activities of the prepared solid superacid
      catalysts were higher than that of the conventional liquid acid H(2)SO(4), and
      that the catalytic activity of mesoporous TiO(2) solid superacid is the highest
      among the three catalysts. Mesoporous TiO(2) solid superacid is a good catalyst
      for the synthesis of isoamyl salicylate or cyclohexanone ethylene ketal.

PMID- 18343572
TI  - Monitoring of decolorization kinetics of Reactive Brilliant Blue X-BR by online
      spectrophotometric method in Fenton oxidation process.
AB  - Online spectrophotometry method is employed to monitor simulated Reactive
      Brilliant Blue X-BR (RBB X-BR) in aqueous solution in Fenton oxidation process.
      The effects of initial dosage of FeSO(4) and H(2)O(2), pH value, initial
      concentration of dye and temperature have been studied. The results show that
      online spectrophotometric method is a quick, feasible and convenient technique to
      monitor color removal of RBB X-BR in Fenton process. The optimal dosage of
      H(2)O(2) and pH is 3.529 mM and 3, respectively. The optimal dosage of Fe(2+) for
      color removal is 0.1618 mM. The concentration of initial FeSO(4) against the
      reaction rate constant (k(ap)) for decolorizing is linear correlation as:
      k(ap)=0.1354[Fe(2+)](o) (R(2)>0.99). The apparent activation energies of reaction
      is 25.21 kJ mol(-1) (R(2)>0.99). The intrinsic reaction rate constant of OH with
      RBB X-BR in aqueous solution is 7.396 x 10(10)M(-1)s(-1). The molecule structure
      of RBB X-BR is decomposed and not mineralized by Fenton's reagent. The main
      intermediate products are 1,2-diacetylenzene and 2,5-diritrobenzoic acid. The
      probable mechanism of the decoloration of RBB X-BR is also discussed.

PMID- 18343574
TI  - Expression of Fos protein in brainstem after application of l-menthol to the rat
      nasal mucosa.
AB  - There are two functional pathways for the nasotrigeminal reflex: the spinal
      nucleus of trigeminal nerve (SPV) to the Kolliker-Fuse (KF) nucleus and the
      nucleus of solitary tract (NTS) to the lateral parabrachial nucleus (PBl).
      Although stimulation of the nasal mucosa by cool temperature induces respiratory
      depression, it is still unknown whether these nuclei are activated. In the
      present study, we examined the expression of Fos protein in rat brainstem neurons
      after nasal application of l-menthol, which is known to activate cold-sensitive
      nasal receptors. Application of l-menthol, but not paraffin oil, decreased the
      respiratory rate from 99.7+/-15.6 to 78.5+/-7.3 min(-1). Furthermore, a
      significantly higher density of Fos-immunoreactive cells was observed in the SPV
      and KF in the l-menthol rats than in the controls. In the SPV, the density of Fos
      immunoreactive cells was highest at approximately 0.5mm rostral to the obex in
      both the l-menthol (48.5+/-11.5 cells/section) and paraffin oil (26.0+/-9.6
      cells/section) groups. In the KF, the mean density of Fos-immunoreactive cells
      was highest at approximately 5.0mm rostral to the obex in both groups (l-menthol:
      67.8+/-14.0 cells/section, control: 41.0+/-12.7 cells/section). The present study
      suggests that the SPV-KF pathway is important for the cold-induced respiratory
      depression.

PMID- 18343575
TI  - Target muscles for retrograde gene delivery to specific spinal cord segments.
AB  - Targeted retrograde gene delivery into the injured spinal cord is less invasive
      for the damaged tissue. One of the advantages of this approach is the possible
      selection of target organs according to the level of spinal cord injury. We
      evaluated nine candidate target organs for retrograde delivery of an adenovirus
      vector carrying beta-galactosidase (AdV-LacZ) gene to cervical, thoracic and
      lumbar spinal cord segments. One week after vector injection into each muscle, we
      assessed the LacZ gene expression in the spinal cord by X-gal staining. The most
      appropriate target organs with high transduction efficacy were the sternomastoid
      and clavotrapezius muscles for cervical spinal cord, tibialis anterior and the
      gastrocnemius muscles for the lumbar spinal cord. Retrograde gene delivery to the
      thoracic spinal cord was inefficient probably due to the small number of anterior
      horn neurons in the region. Gene expression was mainly identified over the
      anatomical area of innervation and not into other body organs. Our results
      suggested that retrograde delivery of adenovirus genome to the cervical and
      lumbar spinal cord segments seems feasible by injection of an adenoviral vector
      into the appropriate target organ. Adenovirus vector is an efficient retrograde
      tracer since it can deliver the carried gene to a wide area of the spinal cord
      and not to other body organs.

PMID- 18343576
TI  - LEDGF binding to stress response element increases alphaB-crystallin expression
      in astrocytes with oxidative stress.
AB  - AlphaB-crystallin, known as a vertebrate lens protein, is a member of the small
      heat shock proteins (sHSP). AlphaB-crystallin is abundantly expressed in the
      vertebrate lens and striated muscles and it is also expressed constitutively in
      other tissues including the central nervous system (CNS). In our previous report,
      we showed alphaB-crystallin induction in activated astrocytes, which are enriched
      in the penumbra after transient focal cerebral ischemia. We also reported that
      alphaB-crystallin is significantly induced in astrocytes in the CA3 region of the
      hippocampus following KA-induced seizure. Here, we report that the expression of
      alphaB-crystallin is upregulated in H2O2-treated primary astrocyte cultures,
      which was prepared from newborn male Sprague-Dawley rats and that the proximal
      408 bp of the alphaB-crystallin promoter harboring stress response element (STRE)
      is responsible for this induction. This effect of H2O2 was found to be virtually
      abolished by introducing mutations into STRE, and these mutations also impaired
      increased lens epithelial derived growth factor (LEDGF) binding to STRE after
      H2O2 treatment. Moreover, LEDGF was induced in primary astrocyte cultures after
      H2O2 treatment and alphaB-crystallin induction was significantly suppressed by
      transfecting small interfering RNA (siRNA) targeting LEDGF. Together these
      results indicate that the H2O2-induced upregulations of alphaB-crystallin in
      astrocytes are mediated by the LEDGF-STRE interaction on alphaB-crystallin
      promoter.

PMID- 18343577
TI  - HSPA5 promoter polymorphisms and risk of Parkinson's disease in Taiwan.
AB  - Endoplasmic reticulum (ER) stress induced by misfolded proteins has been
      implicated in Parkinson's disease (PD) pathogenesis. A malfunction of unfolded
      protein response (UPR) to ER stress can result in PD as well as other
      neurodegenerative diseases. Heat shock 70 kDa protein 5 (HSPA5) is one of the UPR
      chaperones reactive to ER stress to block the apoptotic process. HSPA5 promoter
      polymorphisms -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G
      (rs3216733) and their derived haplotypes may affect promoter activity of the
      gene. This study examines whether these HSPA5 promoter polymorphisms are
      associated with the risk of Taiwanese PD and the age of disease onset using a
      case-control study. Polymorphisms -415 G/A and -180 del/G were completely linked
      in our population (D'=1.00, Delta(2)=1.00). The genotype or allele frequency
      distribution of each HSPA5 polymorphism was not significantly different between
      the controls (n=341) and the PD patients (n=393). Neither the linked -415 G/A and
      -180 del/G nor -370 C/T polymorphism influences PD onset age. Our data suggest
      that the HSPA5 -415 G/A, -370 C/T, and -180 del/G polymorphisms are unlikely to
      play a major role in risk of developing PD in Taiwan.

PMID- 18343578
TI  - Beta-catenin siRNA inhibits ischemia-induced striatal neurogenesis in adult rat
      brain following a transient middle cerebral artery occlusion.
AB  - Beta-catenin, a protein that functions in both cell adhesion and Wnt signaling,
      plays vital roles in mammalian neural development. To investigate the roles of
      beta-catenin in stroke-induced neurogenesis, we injected beta-catenin siRNA into
      ipsilateral ischemic lateral ventricle. We found that inactivation of beta
      catenin by siRNA caused the decline of beta-catenin in the ischemic striatum,
      enlarged stroke-induced infarct volume, reduced SVZ expansion, and inhibited
      striatal neurogenesis in adult rat brain following a transient middle cerebral
      artery occlusion (tMCAO). These results show that beta-catenin-mediated
      transcriptional activation functions in the decision of subventricular zone
      precursors to proliferate or differentiate during stroke-induced striatal
      neurogenesis, and suggest that the signaling activity of beta-catenin may control
      the production of newborn neurons and thus regulate the autonomous repair in the
      striatum after ischemia.

PMID- 18343579
TI  - Modulation of EMG power spectrum frequency during motor imagery.
AB  - To provide evidence that motor imagery (MI) is accompanied by improvement of
      intramuscular conduction velocity (CV), we investigated surface electromyographic
      (EMG) activity of 3 muscles during the elbow flexion/extension. Thirty right
      handed participants were asked to lift or to imagine lifting a weighted dumbbell
      under 3 types of muscular contractions, i.e. concentric, isometric and eccentric,
      taken as independent variables. The EMG activity of the agonist (long and short
      heads of biceps brachii) and the antagonist (long portion of triceps brachii)
      muscles was recorded and processed to determine the median frequency (MF) of EMG
      power spectrum as dependant variable. The MF was significantly higher during the
      MI sessions than during the resting condition while the participants remained
      strictly motionless. Moreover, the MF during imagined concentric contraction was
      significantly higher than during the eccentric. Thus, the MF variation was
      correlated to the type of contraction the muscle produced. During MI, the EMG
      patterns corresponding to each type of muscle contraction remained comparable to
      those observed during actual movement. In conclusion, specific motor programming
      is hypothesized to be performed as a function of muscle contraction type during
      MI.

PMID- 18343580
TI  - Neuroprotective effect of neural stem cell-conditioned media in in vitro model of
      Huntington's disease.
AB  - Although neural stem cell (NSC) transplantation has been investigated as a
      promising tool for reconstituting damaged brains, recent evidences suggest that
      NSCs may rescue the brain via paracrine effects rather than by direct cell
      replacements. In this study, we attempted to determine the neuroprotective effect
      of NSC-conditioned media (NSC-CM) in in vitro model of Huntington's disease.
      Cerebral hybrid neurons (A1) were transfected with either wild-type huntingtin
      (18 CAG repeats) or mutant huntingtin (100 CAG repeats). At 24h after the
      transfection, immunocytochemical patterns of the huntingtin aggregations, as well
      as the level of N-terminal proteolytic cleavages of huntingtin were analyzed.
      Neuronal apoptosis was evaluated with flowcytometry after Annexin-V and propidium
      iodide (PI) staining. Cerebral hybrid neurons transfected with mutant huntingtin
      showed five aggregates patterns, including diffuse cytoplasmic, dispered
      vacuoles, perinuclear vacuoles, nuclear inclusions (NI), and cytoplasmic
      inclusions (CI). NSC-CM reduced the levels of nuclear and cytoplasmic inclusions.
      The transfection with mutant huntingtin increased the level of N-terminal
      cleavages, which was reduced by the NSC-CM treatment. In addition, NSC-CM reduced
      the Annexin-V(+)PI(+) and Annexin-V(+)PI(-) neurons which were induced by the
      mutant huntingtin transfection. In summary, NSC-CM was neuroprotective in in
      vitro model of Huntington's disease with modulating mutant huntingtin-induced
      cytotoxicity.

PMID- 18343581
TI  - Muscarinic receptor activation potentiates the effect of spinal cord stimulation
      on pain-related behavior in rats with mononeuropathy.
AB  - Spinal cord stimulation (SCS) has proven to be a valuable treatment in
      neuropathic pain. Our previous animal experiments performed on rat models of SCS
      and ensuing clinical trials have demonstrated that intrathecal (i.t.)
      administration of subeffective doses of certain drugs may enhance the pain
      relieving effect of SCS in cases with unsatisfactory SCS outcome. Recently, an
      augmented release of spinal acetylcholine acting on muscarinic receptors has been
      shown to be one of the mechanisms involved in SCS. The present study was
      performed to examine whether cold hypersensitivity and heat hyperalgesia in rats
      with partial sciatic nerve injuries can be attenuated by SCS in the same way as
      tactile hypersensitivity and to explore a possibly synergistic effect of SCS and
      a muscarinic receptor agonist, oxotremorine. Rats with signs of neuropathy were
      subjected to SCS applied in awake, freely moving condition. Oxotremorine was
      administered intrathecally. Tactile, cold and heat sensitivities were assessed by
      using von Frey filaments, cold spray and focused radiant heat, respectively.
      Oxotremorine i.t. dose-dependently suppressed the tactile hypersensitivity. SCS
      markedly increased withdrawal thresholds (WTs), withdrawal latencies and cold
      scores. When combining SCS with a subeffective dose of oxotremorine i.t., the
      suppressive effect of SCS on the pain-related symptoms was dramatically enhanced
      in rats failing to obtain a satisfactory effect with SCS alone. In conclusion,
      the combination of SCS and a drug with selective muscarinic receptor agonistic
      properties could be an optional therapy, when SCS per se has proven inefficient.

PMID- 18343582
TI  - Beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1)-mediated changes of
      endogenous amyloid beta in wild-type and transgenic mice in vivo.
AB  - Beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1) initiates
      generation of amyloid beta (Abeta), a pathological hallmark of Alzheimer's
      disease. We investigated the impact of BACE1 protein level on endogenous Abeta.
      Endogenous Abeta and BACE1 protein levels were concurrently and significantly
      reduced during early life. However, Abeta levels were similar between BACE1
      transgenic and wildtype mice. This suggests that BACE1 protein level has a
      minimal effect on the level of endogenous Abeta. Consequently, other factors must
      be involved in modulation of Abeta production in adult and ageing brain and
      investigation of such factors may yield therapeutic targets. Further, these
      results suggest that substantial inhibition of BACE1 in brain may be required for
      clinical benefit in Alzheimer's disease.

PMID- 18343583
TI  - Optimization of specimen preparation of thin cell section for AFM observation.
AB  - High resolution imaging of intracellular structures of ultrathin cell section
      samples is critical to the performance of precise manipulation by atomic force
      microscopy (AFM). Here, we test the effect of multiple factors during section
      sample preparation on the quality of the AFM image. These factors include the
      embedding materials, the annealing process of the specimen block, section
      thickness, and section side. We found that neither the embedding materials nor
      the temperature and speed of the annealing process has any effect on AFM image
      resolution. However, the section thickness and section side significantly affect
      the surface topography and AFM image resolution. By systematically testing the
      image quality of both sides of cell sections over a wide range of thickness (40
      1000 nm), we found that the best resolution was obtained with upper-side sections
      approximately 50-100 nm thick. With these samples, we could observe precise
      structure details of the cell, including its membrane, nucleoli, and other
      organelles. Similar results were obtained for other cell types, including
      Tca8113, C6, and ECV-304. In brief, by optimizing the condition of ultrathin cell
      section preparation, we were able to obtain high resolution intracellular AFM
      images, which provide an essential basis for further AFM manipulation.

PMID- 18343584
TI  - Phosphorylation of tau and alpha-synuclein in synaptic-enriched fractions of the
      frontal cortex in Alzheimer's disease, and in Parkinson's disease and related
      alpha-synucleinopathies.
AB  - Phosphorylation of tau and phosphorylation of alpha-synuclein are crucial
      abnormalities in Alzheimer's disease (AD) and alpha-synucleinopathies
      (Parkinson's disease: PD, and dementia with Lewy bodies: DLB), respectively. The
      presence and distribution of phospho-tau were examined by sub-fractionation, gel
      electrophoresis and Western blotting in the frontal cortex of cases with AD at
      different stages of disease progression, PD, DLB pure form and common form, and
      in age-matched controls. Phospho-tauSer396 has been found in synaptic-enriched
      fractions in AD frontal cortex at entorhinal/transentorhinal, limbic and
      neocortical stages, thus indicating early tau phosphorylation at the synapses in
      AD before the occurrence of neurofibrillary tangles in the frontal cortex.
      Phospho-tauSer396 is also found in synaptic-enriched fractions in the frontal
      cortex in PD and DLB pure and common forms, thus indicating increased tau
      phosphorylation at the synapses in these alpha-synucleinopathies. Densitometric
      studies show between 20% and 40% phospho-tauSer396, in relation with tau-13, in
      synaptic-enriched fractions of the frontal cortex in AD stages I-III, and in PD
      and DLB. The percentage reaches about 95% in AD stage V and DLB common form. Yet
      tau phosphorylation characteristic of neurofibrillary tangles, as revealed with
      the AT8 antibody, is found in the synaptic fractions of the frontal cortex only
      at advanced stages of AD. Increased phosphorylated alpha-synucleinSer129 levels
      are observed in the synaptic-enriched fractions of the frontal cortex in PD and
      DLB pure and common forms, and in advanced stages of AD. Since tau
      hyperphosphorylation has implications in microtubule assembly, and
      phosphorylation of alpha-synuclein at Ser129 favors alpha-synuclein aggregation,
      it can be suggested that synapses are targets of abnormal tau and alpha-synuclein
      phosphorylation in both groups of diseases. Tau phosphorylation at Ser396 has
      also been found in synaptic-enriched fractions in 12-month-old transgenic mice
      bearing the A53T alpha-synuclein mutation.

PMID- 18343585
TI  - Regional distribution and effects of postmortal delay on endocannabinoid content
      of the human brain.
AB  - Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been
      determined in 16 regions and nuclei from human brains, using liquid
      chromatography/in-line mass spectrometry. Measurements in brain samples stored at
      -80 degrees C for 2 months to 13 years indicated that endocannabinoids were
      stable under such conditions. In contrast, the postmortal delay had a strong
      effect on brain endocannabinoid levels, as documented in brain samples
      microdissected and frozen 1-6 h postmortem, and in neurosurgical samples 0, 5,
      30, 60, 180 and 360 min after their removal from the brain. The tissue levels of
      AEA increased continuously and in a region-dependent manner from 1 h after death,
      increasing about sevenfold by 6 h postmortem. In contrast, concentrations of 2
      AG, which were 10-100 times higher in human brain regions than those of AEA,
      rapidly declined: within the first hour, 2-AG levels dropped to 25-35% of the
      initial ('0 min') value, thereafter they remained relatively stable. As analyzed
      in samples removed 1-1.5 h postmortem, AEA levels ranged from a high of 96.3
      fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/mg in the
      cerebellum. 2-AG levels varied eightfold, from 8.6 pmol/mg in the lateral
      hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and
      2-AG varied from region to region, with the 2-AG:AEA ratio being high in the
      sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the
      lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the
      striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid
      content in brain samples of variable postmortal delay, and document differential
      distribution of the two main endocannabinoids in the human brain.

PMID- 18343586
TI  - Hypovolemic shock: critical involvement of a projection from the ventrolateral
      periaqueductal gray to the caudal midline medulla.
AB  - Previous research has suggested that the ventrolateral column of the
      periaqueductal gray (vlPAG) plays a crucial role in triggering a decompensatory
      response (sympathoinhibition, hypotension, bradycardia) to severe blood loss.
      vlPAG excitation triggers also quiescence, decreased vigilance and decreased
      reactivity, the behavioral response which usually accompanies hypovolemic shock.
      The aim of this study was to identify, in unanesthetized rats, the main
      descending pathway(s) via which vlPAG neurons trigger sympathoinhibition and
      bradycardia in response to severe blood loss. Firstly, immediate early gene (c
      Fos) expression was used to identify vlPAG neurons selectively activated by
      severe blood loss. Subsequently, the specific medullary projections of these
      vlPAG neurons were defined by combined c-Fos, retrograde tracing (double-label)
      experiments. It was found that vlPAG neurons selectively activated by severe
      hemorrhage project overwhelmingly to the vasodepressor portion of the caudal
      midline medulla (CMM). Previous studies indicate that this CMM region mediates
      behaviorally-coupled cardiovascular adjustments and the findings described here
      fit with the idea that CMM neurons are uniquely recruited by salient challenges,
      the adaptive responses to which require more than reflexive homeostatic
      cardiovascular adjustments.

PMID- 18343587
TI  - Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation.
AB  - The strength of synapses between auditory nerve (AN) fibers and ventral cochlear
      nucleus (VCN) neurons is an important factor in determining the nature of neural
      integration in VCN neurons of different response types. Synaptic strength was
      analyzed using cross-correlation of spike trains recorded simultaneously from an
      AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as
      chopper, primarylike, and onset using previously defined criteria, although onset
      neurons usually were not analyzed because of their low discharge rates. The
      correlograms showed an excitatory peak (EP), consistent with monosynaptic
      excitation, in AN-VCN pairs with similar best frequencies (49% 24/49 of pairs
      with best frequencies within +/-5%). Chopper and primarylike neurons showed
      similar EPs, except that the primarylike neurons had shorter latencies and
      shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical
      bushy cells were not observed, probably because of the low probability of
      recording from one. The small EPs observed in primarylike neurons, presumably
      spherical bushy cells, could be derived from small terminals that accompany end
      bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were
      consistent with the smaller synaptic terminals on multipolar and globular bushy
      cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of
      threshold, showing that VCN responses to steady tones shift from a 1:1
      relationship between AN and VCN spikes at low sound levels to a more autonomous
      mode of firing at high levels. In the high level mode, the pattern of output
      spikes seems to be determined by the properties of the postsynaptic spike
      generator rather than the input spike patterns. The EP amplitudes did not change
      significantly when the presynaptic spike was preceded by either a short or long
      interspike interval, suggesting that synaptic depression and facilitation have
      little effect under the conditions studied here.

PMID- 18343588
TI  - Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine
      receptors in the striatum.
AB  - Evidence indicates that dopamine receptors regulate processes of procedural
      learning in the sensorimotor striatum. Our previous studies revealed that the
      indirect dopamine receptor agonist cocaine alters motor-skill learning-associated
      gene regulation in the sensorimotor striatum. Cocaine-induced gene regulation in
      the striatum is principally mediated by D1 dopamine receptors. We investigated
      the effects of cocaine and striatal D1 receptor antagonism on motor-skill
      learning. Rats were trained on a running wheel (40-60 min, 2-5 days) to learn a
      new motor skill, that is, the ability to control the movement of the wheel.
      Immediately before each training session, the animals received an injection of
      vehicle or cocaine (25 mg/kg, i.p.), and/or the D1 receptor antagonist SCH-23390
      (0, 3, 10 microg/kg, i.p., or 0, 0.3, 1 microg, intrastriatal via chronically
      implanted cannula). The animal's ability to control/balance the moving wheel
      (wheel skill) was tested before and repeatedly after the training. Normal wheel
      skill memory lasted for at least 4 weeks. Cocaine administered before the
      training tended to attenuate skill learning. Systemic administration of SCH-23390
      alone also impaired skill learning. However, cocaine given in conjunction with
      the lower SCH-23390 dose (3 microg/kg) reversed the inhibition of skill learning
      produced by the D1 receptor antagonist, enabling intact skill performance during
      the whole post-training period. In contrast, when cocaine was administered with
      the higher SCH-23390 dose (10 microg/kg), skill performance was normalized 1-6
      days after the training, but these rats lost their improved wheel skill by day 18
      after the training. Similar effects were produced by SCH-23390 (0.3-1 microg)
      infused into the striatum. Our results indicate that cocaine interferes with
      normal motor-skill learning, which seems to be dependent on optimal D1 receptor
      signaling. Furthermore, our findings demonstrate that D1 receptors in the
      striatum are critical for consolidation of long-term skill memory.

PMID- 18343589
TI  - Morphological and biochemical signs of age-related neurodegenerative changes in
      klotho mutant mice.
AB  - Klotho mutant mice, defective in the klotho gene, develop multiple age-related
      disorders with very short lifespans. Introduction of the exogenous klotho gene
      into these mutant mice leads to an improvement in their phenotypes, while
      overexpression of this gene in wild-type mice significantly extends their
      lifespan. These observations suggest that the klotho gene/protein has an anti
      aging function. Since there have been only a few reports with some disagreement
      about results on the CNS of the mutant mice, we tried to clarify whether the CNS
      neurons generate aging-like features, even in premature stages, using biochemical
      and morphological approaches. Results obtained from the mutant mice, when
      compared with wild-type mice, were as follows. Neurofilaments (NFs) were
      increased significantly in axons, with the subunit proteins showing a significant
      enhancement in phosphorylation or expression of NF-H or NF-L, respectively.
      Microtubules in Purkinje cell dendrites were closer to each other, and in the CNS
      tissue tubulin was unaltered, but microtubule-associated protein (MAP) 2 was
      significantly reduced in expression. Neuronal cellular organelles were
      morphologically disordered. Lysosomes, cathepsin D and light chain 3 of MAP1A/B
      (LC3) were augmented with the appearance of putative autophagy-related
      structures. Antiapoptotic Bcl-xL and proapoptotic Bax were reduced and enhanced,
      respectively, and mitogen-activated protein kinase was reduced. Synapse-related
      proteins and structures were decreased. Neuronal degeneration was evident in
      hippocampal pyramidal cells, and possibly in Purkinje cells. Astrocytic glial
      filaments and glial fibrillary acidic protein were increased in density and
      expression, respectively. Together, the CNS neuronal alterations in klotho mutant
      mice were quite similar to those found in aged animals, including even premature
      death, so this mouse should be a more appropriate animal model for CNS aging than
      those previously reported.

PMID- 18343590
TI  - Ethanol dually modulates GABAergic synaptic transmission onto dopaminergic
      neurons in ventral tegmental area: role of mu-opioid receptors.
AB  - The mesolimbic dopaminergic system, originating from the ventral tegmental area
      (VTA) is implicated in the rewarding properties of ethanol. VTA dopaminergic
      neurons are under the tonic control of GABAergic innervations. Application of
      GABAergic agents changes ethanol consumption. However, it is unclear how acute
      ethanol modulates GABAergic inputs to dopaminergic neurons in the VTA. This
      report describes ethanol at clinically relevant concentrations (10-40 mM) dually
      modulates inhibitory postsynaptic currents (IPSCs). IPSCs were mediated by
      GABA(A) receptors and were recorded from VTA dopaminergic neurons in acute
      midbrain slices of rats. Acute application of ethanol reduced the amplitude and
      increased the paired pulse ratio of evoked IPSCs. Ethanol lowered the frequency
      but not the amplitude of spontaneous IPSCs. Nevertheless, ethanol had no effect
      on miniature IPSCs recorded in the presence of tetrodotoxin. These data indicate
      that ethanol inhibits GABAergic synaptic transmission to dopaminergic neurons by
      presynaptic mechanisms, and that ethanol inhibition depends on the firing of
      GABAergic neurons. Application of CGP 52432, a GABA(B) receptor antagonist, did
      not change ethanol inhibition of IPSCs. Tyr-d-Ala-Gly-N-Me-Phe-Gly-ol enkephalin
      (DAMGO), a mu-opioid receptor agonist, conversely, silenced VTA GABAergic neurons
      and inhibited IPSCs. Of note, in the presence of a saturating concentration of
      DAMGO (3 microM), ethanol potentiated the remaining IPSCs. Thus, ethanol dually
      modulates GABAergic transmission to dopaminergic neurons in the VTA. Ethanol
      modulation depends on the activity of VTA GABAergic neurons, which were inhibited
      by the activation of mu-opioid receptors. This dual modulation of GABAergic
      transmission by ethanol may be an important mechanism underlying alcohol
      addiction.

PMID- 18343591
TI  - Chronic hypoxia-induced alteration of presynaptic protein profiles and
      neurobehavioral dysfunction are averted by supplemental oxygen in Lymnaea
      stagnalis.
AB  - Chronic hypoxia causes neural dysfunction. Oxygen (O(2)) supplements have been
      commonly used to increase the O(2) supply, yet the therapeutic benefit of this
      treatment remains controversial due to a lack of cellular and molecular evidence.
      In this study, we examined the effects of short-burst O(2) supplementation on
      neural behavior and presynaptic protein expression profiles in a simple chronic
      hypoxia model of snail Lymnaea stagnalis. We reported that hypoxia delayed the
      animal response to light stimuli, suppressed locomotory activity, induced
      expression of stress-response proteins, hypoxia inducible factor-1alpha (HIF
      1alpha) and heat shock protein 70 (HSP70), repressed syntaxin-1 (a membrane-bound
      presynaptic protein) and elevated vesicle-associated membrane protein-1 (VAMP-1)
      (a vesicle-bound presynaptic protein) level. O(2) supplements relieved
      suppression of neural behaviors, and corrected hypoxia-induced protein
      alterations in a dose-dependent manner. The effectiveness of supplemental O(2)
      was further evaluated by determining time courses for recovery of neural
      behaviors and expression of stress response proteins and presynaptic proteins
      after relief from hypoxia conditions. Our findings suggest that O(2) supplement
      improves hypoxia-induced adverse alterations of presynaptic protein expression
      and neurobehaviors, however, the optimal level of O(2) required for improvement
      is protein specific and system specific.

PMID- 18343592
TI  - Morphine produces circuit-specific neuroplasticity in the bed nucleus of the
      stria terminalis.
AB  - The bed nucleus of the stria terminalis (BST) is a brain structure located at the
      interface of the cortex and the cerebrospinal trunk. The BST is a cluster of
      nuclei organized in a complex intrinsic network that receives inputs from
      cortical and subcortical sources, and that sends a widespread top-down
      projection. There is growing evidence that the BST is a key component in the
      neurobiological basis of substance abuse. In the present study, the regulation of
      excitatory inputs onto identified neurons in the BST was examined in rats treated
      chronically with morphine. Neurons projecting to the ventral tegmental area (VTA)
      were identified by retrograde transport of fluorescent microspheres and recorded
      in the whole-cell voltage clamp configuration in brain slices. Selective
      excitatory inputs to these neurons were electrically evoked with electrodes
      placed in the medial and lateral aspects of the dorsal BST. The chronic morphine
      treatment selectively increased AMPA-dependent excitatory postsynaptic currents
      in a subset of inputs activated by dorso-lateral stimulation in the BST. Inputs
      activated by medial stimulation were not affected by morphine. Likewise, the
      inputs to neurons that did not project to the VTA were not changed by morphine.
      Altogether, these results extend the understanding of neuronal circuits
      intrinsically sensitive to drugs of abuse within the BST.

PMID- 18343593
TI  - Sulfhydryl oxidation: a potential strategy to achieve neuroprotection during
      severe hypoxia?
AB  - Previously we reported that sulfhydryl (SH) modulation affects the susceptibility
      of rat hippocampal slices to severe hypoxia. SH-oxidation by DTNB (5,5'-dithiobis
      2-nitrobenzoic acid) or H2O2 postponed the onset of hypoxia-induced spreading
      depression (HSD), thereby delaying the loss of neuronal function, whereas SH
      reduction by DTT (1,4-dithio-dl-threitol) hastened HSD onset. To judge the
      neuroprotective merit that might arise from a postponement of HSD by oxidants, we
      have extended our earlier observations by multiparametric recordings and screened
      for changes in the extracellular K+ accumulation, HSD propagation velocity, and
      its maximum spread. As parameters for neuronal network function, the failure of
      synapses during hypoxia and their posthypoxic recovery were analyzed. DTNB (2 mM)
      or H2O2 (5 mM) postponed HSD but did not attenuate the rise in extracellular K+
      concentration ([K+](o)), HSD propagation velocity or its maximum spread. H2O2
      slightly postponed the synaptic failure during hypoxia; the posthypoxic recovery
      of synapses was, however, incomplete. DTNB slowed the synaptic recovery upon
      reoxygenation. DTT (2 mM) hastened HSD onset, but HSD propagation velocity and
      tissue invasion were not affected. Upon reoxygenation, however, normalization of
      [K+](o) was disturbed and synaptic recovery failed. Therefore, SH-reducing
      conditions at the onset of HSD proved to be devastating for the hippocampal
      network. In conclusion, the only merit of DTNB or H2O2 treatment is a delayed HSD
      onset, i.e. some extra time before neuronal function is lost during severe
      hypoxia. Attenuation of the severe changes during HSD or an improved outcome was
      not observed. Nevertheless, combination of SH-oxidants with established
      neuroprotectants might be a potential therapeutic approach.

PMID- 18343595
TI  - Presynaptic actions of opioid receptor agonists in ventromedial hypothalamic
      neurons in estrogen- and oil-treated female mice.
AB  - Estrogens act upon ventromedial hypothalamic (VMH) neurons, and their effects on
      female arousal and sexual behaviors mediated by VMH neurons involve several
      neurotransmitters and neuromodulators. Among these are opioid peptides which
      might be predicted to oppose estrogenic action on VMH because they tend to
      decrease CNS arousal. Spontaneous excitatory postsynaptic currents were recorded
      from VMH neurons from 17beta-estradiol- (E, 10 mug/0.1 ml) or oil-treated control
      ovariectomized (OVX) mice using whole-cell patch-clamp techniques. To examine the
      impact of opioidergic inputs, recordings of neurons from both treatment groups
      were obtained in the presence of the general opioid receptor agonist methionine
      enkephalin-Arg-Phe (MERF, 3 muM), or mu-receptor specific agonist [d-Ala(2), N-Me
      Phe(4), Gly(5)-ol]-enkephalin (DAMGO, 1 muM). Compared with oil, E treatment for
      48 h significantly increased the frequency of spontaneous excitatory postsynaptic
      currents (sEPSCs) without affecting their amplitude. MERF and DAMGO each
      abolished this E effect, causing significant reductions in sEPSCs. The effect of
      MERF was abolished by naltrexone (general opioid receptor antagonist, 3 muM) and
      the effect of DAMGO by d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP) (mu
      opioid receptor selective antagonist, 1 muM); in contrast, kappa- and delta
      opioid receptor agonists, U69593 (300 nM) and [d-Pen(2),d-Pen(5)]-enkephalin
      (DPDPE, 1 muM) respectively, had little effect on the sEPSCs compared with DAMGO.
      To consider presynaptic vs. postsynaptic effects of opioids, miniature excitatory
      postsynaptic currents (mEPSCs) were investigated in E- and oil-treated VMH
      neurons and opioid receptor antagonist effects on mEPSCs were observed. Both MERF
      and DAMGO reduced the frequency of mEPSCs, but had no effect on their amplitude.
      Our findings indicate that opioids suppress excitatory synaptic transmissions in
      VMH neurons primarily through mu-receptors and could thereby decrease sexual
      arousal in mice.

PMID- 18343596
TI  - Rats with high or low sociability are differently affected by chronic variable
      stress.
AB  - Depression is strongly related to social behavior. We have previously shown that
      social behavior of rats is individually stable. The purpose of the present study
      was to compare the sensitivity of animals with different sociability to chronic
      variable stress (CVS). Four social interaction tests were performed with 60
      single-housed male Sprague-Dawley rats. Twenty rats with the lowest and 20 with
      the highest average social activity time were selected as low sociability (LS)
      and high sociability (HS) rats, respectively. Both groups were further divided
      into control and stress groups with equal average body weight. The CVS procedure
      lasted for 3 weeks. The stressors applied were cold water and wet bedding,
      imitation of injection, stroboscopic light, movement restriction in a small cage,
      tail pinch with a clothespin, and strong illumination during the predicted dark
      phase. In HS-rats, but not in LS-rats, CVS reduced sucrose intake compared with
      baseline after 3 weeks, suggesting that HS-rats are more vulnerable to anhedonia
      elicited by CVS. LS-animals were more anxious in the social interaction and open
      field tests, but stress eliminated differences with HS-animals in the social
      interaction test and increased their activity in the forced swimming test. In LS
      rats stress increased ex vivo dopamine levels and reduced 5-HT levels in the
      frontal cortex, suggesting that the increased behavioral activity after stress
      may be related to increased impulsivity. This study thus revealed that animals
      with high sociability trait are more vulnerable to anhedonia elicited by chronic
      stress in conditions of single housing.

PMID- 18343597
TI  - Gene mutation might contribute to carcinogenesis by disrupting the asymmetric
      division of somatic stem cells.

PMID- 18343594
TI  - Distribution and phenotypes of unipolar brush cells in relation to the granule
      cell system of the rat cochlear nucleus.
AB  - In most mammals the cochlear nuclear complex (CN) contains a distributed system
      of granule cells (GCS), whose parallel fiber axons innervate the dorsal cochlear
      nucleus (DCN). Like their counterpart in cerebellum, CN granules are innervated
      by mossy fibers of various origins. The GCS is complemented by unipolar brush
      (UBCs) and Golgi cells, and by stellate and cartwheel cells of the DCN. This
      cerebellum-like microcircuit modulates the activity of the DCN's main projection
      neurons, the pyramidal, giant and tuberculoventral neurons, and is thought to
      improve auditory performance by integrating acoustic and proprioceptive
      information. In this paper, we focus on the rat UBCs, a chemically heterogeneous
      neuronal population, using antibodies to calretinin, metabotropic glutamate
      receptor 1alpha (mGluR1alpha), epidermal growth factor substrate 8 (Eps8) and the
      transcription factor T-box gene Tbr2 (Tbr2). Eps8 and Tbr2 labeled most of the
      CN's UBCs, if not the entire population, while calretinin and mGluR1alpha
      distinguished two largely separate subsets with overlapping distributions. By
      double labeling with antibodies to Tbr2 and the alpha6 GABA receptor A (GABAA)
      subunit, we found that UBCs populate all regions of the GCS and occur at
      remarkably high densities in the DCN and subpeduncular corner, but rarely in the
      lamina. Although GCS subregions likely share the same microcircuitry, their
      dissimilar UBC densities suggest they may be functionally distinct. UBCs and
      granules are also present in regions previously not included in the GCS, namely
      the rostrodorsal magnocellular portions of ventral cochlear nucleus, vestibular
      nerve root, trapezoid body, spinal tract and sensory and principal nuclei of the
      trigeminal nerve, and cerebellar peduncles. The UBC's dendritic brush receives
      AMPA- and NMDA-mediated input from an individual mossy fiber, favoring
      singularity of input, and its axon most likely forms several mossy fiber-like
      endings that target numerous granule cells and other UBCs, as in the cerebellum.
      The UBCs therefore, may amplify afferent signals temporally and spatially,
      synchronizing pools of target neurons.

PMID- 18343598
TI  - Maspin overexpression correlates with increased expression of vascular
      endothelial growth factors A, C, and D in human ovarian carcinoma.
AB  - The vascular endothelial growth factor (VEGF) family, including VEGFA, VEGFC, and
      VEGFD, plays an essential role in the angiogenesis of both pathologic and
      nonpathologic conditions. Maspin belongs to the serpin superfamily and has been
      identified as a tumor suppressor because it inhibits motility, invasion, and
      angiogenesis. Few studies have compared maspin with VEGF in ovarian carcinoma.
      Therefore, we investigated the expression and correlation of maspin, VEGFA,
      VEGFC, and VEGFD with the tumorigenesis of the ovary and clinicopathologic
      variables. Using immunohistochemistry, we examined maspin, VEGFA, VEGFC, and
      VEGFD expression in 60 ovarian carcinoma tissues (35 serous papillary carcinomas,
      18 endometrioid carcinomas, and 7 primary ovarian mucinous carcinomas). Staining
      of cells was scored as +2 if more than 50% of the cells were positive, as +1 if
      less than 50% of the cells were positive, and as negative if none of the cells
      stained positive. Overexpression of maspin, VEGFC, and VEGFD was significantly
      associated with high tumor grade (P<.001, P=.004, P<.001, respectively), clinical
      stage (P=.002, .01, and .001, respectively), the presence of ascites (P<.001,
      P=.03, and P=.001, respectively), and the presence of metastatic lymph nodes
      (P=.002, P<.001, and P<.001, respectively). Maspin was correlated with VEGFA
      (P=.01), VEGFC (P<.001), and VEGFD (P<.001). The VEGFA score was positively
      correlated with high tumor grade (P=.04), lymphovascular space invasion (LVSI)
      (P<.001), International Federation of Gynecology and Obstetrics (FIGO) stage
      (P=.009), maspin, VEGFC (P=.003), and VEGFD (P=.003), but it was not correlated
      with the presence of ascites and metastatic lymph nodes. Maspin, VEGFC, and VEGFD
      are expressed in ovarian tumors with a poor prognostic parameters, and seem to
      play a role in ovarian cancer angiogenesis, progression, and lymph node
      metastases. Our results indicate that in contrast to most other carcinomas,
      maspin expression is directly associated with the biological aggressiveness of
      ovarian carcinoma. These results may offer new insights regarding the role of
      maspin in ovarian cancer and might also affect the diagnosis and treatment
      strategies.

PMID- 18343599
TI  - A case of intraosseous arteriovenous malformation with unusual radiological
      presentation of low blood flow.
AB  - We report a case of intraosseous arteriovenous malformation (AVM) arising in the
      diaphysis of the tibia. The patient was a 15-year-old boy who presented with pain
      in the right lower leg for 3 years. Plain radiographs displayed honeycomb lytic
      lesions in the right tibial shaft, with slight expansion of the bone and cortical
      thinning. The lesion was isointense to the muscle on T1-weighted images, and
      hyperintense on T2-weighted images. An admixture of hypointense small nodular or
      linear areas on both T1- and T2-weighted images was present within the lesion.
      Post contrast fat-suppressed T1-images demonstrated a mild heterogeneous increase
      in signal intensity throughout the tumor. Angiographs showed only faint staining
      in the lesion. Curettage of the lesion was carried out, and the histological
      diagnosis of AVM was made. In the context of this patient's lesion, it should be
      noted that AVM rarely presents as an intraosseous lesion with low blood flow.

PMID- 18343600
TI  - Tongan perceptions of cancer.
AB  - BACKGROUND: There is little published information about cancer-related knowledge,
      attitudes, and preventive behaviors of Tongans in the United States. The purpose
      of this study was to evaluate answers to the following questions: What is cancer?
      What causes cancer? And what can you do to prevent cancer? METHODS: We completed
      face-to-face, semi-structured interviews with 48 self-reported Tongans (16 men
      and 32 women) over the age of 18 years, selected through non-probability
      purposive sampling with help from Tongan community-based organizations. The
      questions regarded demographic characteristics, and cancer-related knowledge,
      attitudes and preventive behaviors. The research settings were San Mateo,
      California and Salt Lake City, Utah. We analyzed the data using qualitative
      content analysis of individual interviews to identify themes. RESULTS: All but
      one of the 48 participants had migrated to the U.S. from Tonga. The average
      income was approximately $3100 per month and average household size was six.
      Fewer than half of participants had health insurance. The theme that cancer was
      equivalent to death was pervasive through all the responses. Weaknesses in the
      body and exposure to toxins in the environment were dominant themes in the
      causation of cancer. Leading a healthy life and prayer were among the preventive
      measures cited by the respondents. CONCLUSION: The association of cancer with
      death is a strong indication that cancer information is not reaching this
      community. Interventions must take this into account and include Tongan cancer
      survivors in order to enhance the effectiveness of early screening efforts.

PMID- 18343601
TI  - Antifungal activity of Agapanthus africanus extractives.
AB  - The ethanolic extract of the rhizomes of Agapanthus africanus showed antifungal
      activity. In bioassay guided fractionation, n-butanol fraction exhibited
      significant activity against human pathogens. A saponin, (25R)-spirost-7-en
      2alpha,3beta,5alpha-triol-3-O-[alpha-L-rhamnopyranosyl(1-->2)-[beta-D
      galactopyranosyl (1-->3)] beta-D-glucopyranoside (1), responsible for the
      antifungal activity and having MIC value of 15.6 microg/ml against Trychophyton
      mentagrophytes and Sporothrix schenekii, was isolated and identified as active
      constituent of the plant.

PMID- 18343602
TI  - [TVT Secur: more and more minimally invasive. Preliminary prospective study of
      110 cases].
AB  - OBJECTIVES: To present a new minimal invasive suburethral tape device derivative
      of the classic TVT, to describe the technique of laying, to evaluate
      complications and results to short term. MATERIALS AND METHODS: Prospective
      multicentric study of 110 patients presenting a stress urinary incontinence and
      benefiting from the laying of TVT Secur without associated operation. The tape is
      identical to that old-fashioned retropubic and obturator TVT, smaller, laying in
      "U" or in "hammock" without orifice of exit, to avoid complications due to
      crossed spaces of the other techniques. The device and the technique of laying
      are described by authors. The originality of the TVT Secur resides in the
      mechanism of insertion of the tape to a metallic divice. All patients have been
      controlled at two months and complications with notably pains (quotation VAS) as
      well as objective results have been reported. RESULTS: Pure and isolated stress
      urinary incontinence for 71 patients, mixed incontinence for 39 and sphincter
      deficient for 23. Preoperative urgency for 49 patients and dysuria for 10 of
      them. The method "hammock" has been used in 85.5% of cases. The type of
      anaesthesia has been pure local for 69.1% (0 to 98.8% for the different centers)
      with an average operative time of 8'30". Under local anaesthesia, the average per
      operative pain was quoted 2.8/10, and 0.7 at the end of intervention.
      Peroperative complications have revealed a wound of bladder, a vaginal wound and
      four bleeding of more than 100ml. In immediate continuations a total retention
      yielding to 24h and 13 postmicturition residual between 100 and 200ml have been
      mentioned. At two months, authors have observed the following: de novo urgency in
      19.6%, de novo dysuria in 13.2%, one tape exposition, one granuloma, one urinary
      infection and seven perceptible lateral cords without pain. Thirteen patients
      have signalled to have had moderated pains on a duration of four to 30 days.
      Early objective results are globally 70.4% of dry patients (83% for pure isolated
      SUI, 72.2% for SUI with deficient sphincter, 50% for mixed incontinence). The
      pure local anaesthesia was recommended by 98% of patients. CONCLUSION: The
      diminution of complications ahead not to be made to the detriment of results, it
      is necessary to envisage multicentric studies with standardized modifications.
      The indications of this new device will have to be defined.

PMID- 18343603
TI  - [Occult cancer and venous thromboembolism: which screening in patients with
      inaugural deep vein thrombosis?].
AB  - The association between thrombosis and cancer, initially evidenced in metastatic
      patients is well recognized and now described in patients with occult cancer
      where venous thrombosis may be the first clinical manifestation (Trousseau's
      syndrome). In this review, clinical and epidemiological interactions between
      thrombosis and cancer are described in five distinct step: venous thrombosis
      during malignancy and occult cancer, period of large increased in the risk for
      diagnosis of cancer, patients or venous thrombosis with increased risk for occult
      cancer, extensive or not extensive screening for occult cancer, earlier occult
      cancer detection associated or not with improved treatment possibilities and thus
      prognosis.

PMID- 18343604
TI  - [Human bocavirus (HBoV)].
AB  - The human bocavirus (HBoV) has been recently identified by means of molecular
      screening techniques in respiratory tract secretions from children with acute
      respiratory tract disease. This virus, which belongs to the Parvoviridae family,
      has been detected worldwide with a 5 to 10% prevalence among children with upper
      or lower respiratory tract infections, essentially during the winter period. A
      seroepidemiological study has shown that almost all the children have antibodies
      to HBoV by the age of five years, and HBoV infection seems to be rare in adults.
      HBoV is often detected in association with other respiratory viruses. This virus
      has also been detected in stools, but its role in gastroenteritis has not been
      yet established. Virological diagnostic of HBoV infection is based on the
      detection of viral DNA by PCR. Viral load determination by viral DNA quantitation
      in respiratory tract secretions could be a tool to differentiate between
      symptomatic HBoV infection and virus carriage.

PMID- 18343605
TI  - [Consciousness disorders and severe haemolytic anaemia in a patient coming from
      overseas].
AB  - A 54-years-old patient coming from Guinea, who presented fever, diarrhoea,
      consciousness disorders and severe haemolytic anaemia, was admitted to
      resuscitation unit in France. Despite many explorations carried out (evaluation
      of traumatic causes, infection, neoplasia, vascular, toxic causes, vitamin
      deficiency), it was not possible to explain neurological symptomatology. Besides,
      haemolytic anaemia was due to the ingestion of metamizole in a context of glucose
      6-phosphate dehydrogenase deficit. This drug's marketing has been suspended in
      France since 2006. Despite appropriate treatment, after seven days of
      hospitalization, the patient died of multi-organ failure and hemophagocytic
      syndrome. This clinical case illustrates the difficulties encountered to set a
      diagnosis and manage patients coming from overseas. Uncommon aetiologies for
      French healthcare professionals should be evoked in the absence of comprehensive
      clinical information.

PMID- 18343606
TI  - No evidence of the APC D1822V missense variant's pathogenicity in Tunisian
      patients with sporadic colorectal cancer.
AB  - OBJECTIVES: Sporadic colorectal cancer is influenced by numerous single
      nucleotide polymorphisms (SNPs), each with minor effects on the cancer risk. This
      study seeks to determine whether there is any association of the I1307K, E1317Q
      and D1822V variants within the Adenomatous polyposis coli gene (APC) and risk to
      develop colorectal cancer in Tunisian population. METHODS: Direct sequencing was
      used to investigate three SNPs in the APC in 48 Tunisian sporadic colorectal
      cancer cases and 63 controls. RESULTS: There was no statistically significant
      association between the I1307K, E1317Q and D1822V variants investigated and
      colorectal cancer risk. CONCLUSION: The lack of association may show that these
      variants selected for this study are not involved in the colorectal carcinogenic
      process. Otherwise, the eventual biological effect is so little to go undetected,
      unless increasing the sample size.

PMID- 18343607
TI  - Effects of a universal classroom behavior management program in first and second
      grades on young adult behavioral, psychiatric, and social outcomes.
AB  - BACKGROUND: The Good Behavior Game (GBG), a method of classroom behavior
      management used by teachers, was tested in first- and second-grade classrooms in
      19 Baltimore City Public Schools beginning in the 1985-1986 school year. The
      intervention was directed at the classroom as a whole to socialize children to
      the student role and reduce aggressive, disruptive behaviors, confirmed
      antecedents of later substance abuse and dependence disorders, smoking, and
      antisocial personality disorder. This article reports on impact to ages 19-21.
      METHODS: In five poor to lower-middle class, mainly African American urban areas,
      three or four schools were matched and within each set randomly assigned to one
      of three conditions: (1) GBG, (2) a curriculum-and-instruction program directed
      at reading achievement, or (3) the standard program. Balanced assignment of
      children to classrooms was made, and then, within intervention schools,
      classrooms and teachers were randomly assigned to intervention or control.
      RESULTS: By young adulthood significant impact was found among males,
      particularly those in first grade who were more aggressive, disruptive, in
      reduced drug and alcohol abuse/dependence disorders, regular smoking, and
      antisocial personality disorder. These results underline the value of a first
      grade universal prevention intervention. REPLICATION: A replication was
      implemented with the next cohort of first-grade children with the same teachers
      during the following school year, but with diminished mentoring and monitoring of
      teachers. The results showed significant GBG impact for males on drug
      abuse/dependence disorders with some variation. For other outcomes the effects
      were generally smaller but in the predicted direction.

PMID- 18343608
TI  - Conservation of a vitellogenin gene cluster in oviparous vertebrates and
      identification of its traces in the platypus genome.
AB  - Vitellogenin (Vtg) derivatives are the main egg-yolk proteins in most oviparous
      animal species, and are, therefore, key players in reproduction and embryo
      development. Conserved synteny and phylogeny were used to identify a Vtg gene
      cluster (VGC) that had been evolutionarily conserved in most oviparous
      vertebrates, encompassing the three linked Vtgs on chicken (Gallus gallus)
      chromosome 8. Tandem arranged homologs to chicken VtgII and VtgIII were retrieved
      in similar locations in Xenopus (Xenopus tropicalis) and homologous transcribed
      inverted genes were found in medaka (Oryzias latipes), stickleback (Gasterosteus
      aculeatus), pufferfish (Takifugu rubripes), and Tetrahodon (Tetraodon
      nigroviridis), while zebrafish (Danio rerio) Vtg3 may represent a residual trace
      of VGC in this genome. Vtgs were not conserved in the paralogous chromosomal
      segment attributed to a whole-genome duplication event in the ancestor of
      teleosts, while tandem duplicated forms have survived the recent African clawed
      frog (Xenopus laevis) tetraploidization. Orthologs to chicken VtgI were found in
      similar locations in teleost fish, as well as in the platypus (Ornithorhynchus
      anatinus). Additional Vtg fragments found suggested that VGC had been conserved
      in this egg-laying mammal. A low ratio of nonsynonymous-to-synonymous
      substitution values and the paucity of pseudogene features suggest functional
      platypus Vtg products. Genomic identification of Vtgs, Apob, and Mtp in this
      genome, together with maximum likelihood and Bayesian inference phylogenetic
      analyses, support the existence of these three large lipid transfer protein
      superfamily members at the base of the mammalian lineage. In conclusion, the
      establishment of a VGC in the vertebrate lineage predates the divergence of ray
      finned fish and tetrapods and the shift in reproductive and developmental
      strategy observed between prototherians and therians may be associated with its
      loss, as shown by its absence from the genomic resources currently available from
      therians.

PMID- 18343609
TI  - Transcription of the LAT gene is regulated by multiple binding sites for Sp1 and
      Sp3.
AB  - The LAT gene encodes an adaptor molecule that links receptor engagement to
      critical downstream signaling events. Previously, we identified the proximal
      promoter for the human LAT gene and found that it contains binding sites for
      members of the Ets and Runx transcription factor families. In the present study,
      we show that the promoter also contains 5 GC-rich elements that contribute to
      promoter activity and that are capable of binding the transcription factors Sp1
      and Sp3. Overexpression of either Sp1 or full-length Sp3 was shown to augment LAT
      promoter activity, while siRNA-mediated knockdown of each transcription factor
      was demonstrated to have an inhibitory effect. We also discovered a cell-type
      specific DNase hypersensitive site that maps to the Sp1/Sp3 and adjacent Ets and
      Runx binding sites. Collectively, these results provide compelling data that
      implicates Sp1 and Sp3 in the transcriptional regulation of the human LAT gene.

PMID- 18343610
TI  - Combined effect of liposomalization and addition of glycerol on the transdermal
      delivery of isosorbide 5-nitrate in rat skin.
AB  - In this report, we investigated the combined effect of drug liposomalization and
      addition of glycerol on the transdermal delivery of isosorbide 5-nitrate (ISN) in
      rat abdominal skin in vitro. Occlusive application of both liposomal and aqueous
      ISN solution, with and without addition of 5% glycerol, showed that drug
      liposomalization and addition of glycerol has far-reaching implications for ISN
      permeation and accumulation in 4 and 8 weeks old rat abdominal skin. Using 8
      weeks old rat abdominal skin, the optimal concentration of glycerol to be added
      to liposomal ISN was found to be 5%. The ISN mean values permeated through and
      accumulated in stripped 8 weeks old rat abdominal skin from those formulations
      described above were not significant different, which might indicate the combined
      effect of glycerol and liposomal ISN resides solely in the stratum corneum (SC).
      Based on previous reports, the enhancement effect of glycerol might be due to an
      increase in the SC hydration, and perhaps due to subtle changes in the lipid
      organization caused by penetration of liposomal lipids within the SC
      intercellular spaces. These data might provide evidence that glycerol action on
      SC is useful to facilitate skin permeation and accumulation of drugs formulated
      in liposome.

PMID- 18343611
TI  - Anatomical plasticity in brainstem auditory nuclei following unilateral ablation
      of the inferior colliculus in neonatal rats.
AB  - Anatomical plasticity of projections from brainstem auditory structures to the
      inferior colliculus (IC) was examined in albino rats to determine the effects of
      unilateral destruction of the IC during early development. The IC in the right
      hemisphere was destroyed by aspiration on postnatal day 3. Upon reaching
      adulthood, the rats were examined by retrograde tract tracing methods with fluoro
      gold (FG) and [3H]-glycine to determine patterns of brainstem projections to the
      undamaged left IC. In our FG experiments, the results confirmed the presence of
      aberrant crossed projections from the right medial superior olive (MSO) to the
      undamaged left IC. Following injections of [3H]-glycine or FG into the undamaged
      left IC, however, no other aberrant projections were found in the superior olive,
      including those from the ipsilateral lateral superior olive (LSO) or the superior
      paraolivary nucleus (SPN). These results suggest that projections from the MSO to
      the IC may have the latent ability to create aberrant crossed projections during
      development. On the other hand, the neurons in LSO and SPN do not form aberrant
      projections following early unilateral IC lesions.

PMID- 18343612
TI  - Anti-HIV-1 activities of compounds isolated from the medicinal plant Rhus
      chinensis.
AB  - AIM OF THE STUDY: Previously, we reported that the petroleum ether fraction, RC
      1, and EtOAc fraction, RC-2, of the medicinal plant Rhus chinensis showed potent
      anti-HIV-1 activities. To address anti-HIV-1 constituents of RC-1 and RC-2, 17
      compounds were isolated. Anti-HIV-1 activities and possible action mechanisms of
      these compounds were investigated. METHODS: The syncytial formation induced by
      HIV-1 was determined under the inverted microscope, cellular toxicity and
      protection assay were assessed by MTT method, reduction of p24 antigen expression
      level and RT activity were measured by ELISA, and inhibition of recombinant HIV-1
      PR was monitored by the fluorescent signal. RESULTS: The compounds 1 and 13
      inhibited HIV-1-induced syncytium formation potently with TI value of 42.31 and
      19.07, respectively. Compounds 4, 5, 6, 9 and 10 were less potent with TI value
      of 8.94, 8.22, 4.14, 5.11 and 5.34, respectively. Compound 1, a benzofuranone
      type compound, previously reported as a novel anti-HIV-1 agent, might target late
      steps of HIV-1 life cycle. Compound 13 inhibited HIV-1 replication with EC(50) of
      7.16mug/ml and might target at/before integration step. CONCLUSION: These
      compounds might contribute to anti-HIV-1 activities extracts of the medicinal
      plant Rhus chinensis.

PMID- 18343613
TI  - Anti-nociceptive effects induced by intrathecal injection of BmK AS, a
      polypeptide from the venom of Chinese-scorpion Buthus martensi Karsch, in rat
      formalin test.
AB  - AIM OF THE STUDY: Asian scorpion Buthus martensi Karsch (BmK) is widely used to
      treat neurological symptoms, especially chronic pain, in traditional Chinese
      medicine for thousands of years. BmK AS, a polypeptide from BmK venom, could
      produce peripheral potent anti-nociceptive effects in rats. In the present study,
      spinal anti-nociceptive effects of BmK AS were investigated in rat formalin test.
      MATERIALS AND METHODS: Spinal anti-nociceptive activity of BmK AS was studied
      using formalin test in rats. BmK AS in doses of 0.02, 0.1 and 0.5 microg was
      administered intrathecally before formalin injection 10 min. The suppression by
      intrathecal injection of BmK AS on formalin-induced spontaneous nociceptive
      behaviors and spinal c-Fos expression were investigated. RESULTS: Intrathecal
      injection of BmK AS markedly reduced formalin-evoked biphasic spontaneous
      nociceptive behaviors in a dose-dependent manner. Formalin-induced c-Fos
      expression could be dose-dependently inhibited by BmK AS in superficial (I-II),
      the nucleus proprius (III and IV) and deep (V-VI) dorsal horn laminae, but not in
      the ventral gray laminae (VII-X) of lumbar spinal cord. The suppression by BmK AS
      on c-Fos expression in superficial laminaes was much stronger than that in deep
      laminaes. CONCLUSION: The present study demonstrates that BmK AS is capable of
      producing remarkable anti-nociceptive effects not only in periphery but also in
      spinal cord.

PMID- 18343614
TI  - Two arch criteria of the ilium for sex determination of immature skeletal
      remains: a test of their accuracy and an assessment of intra- and inter-observer
      error.
AB  - Although the assignment of sex to immature skeletal remains is considered
      problematic, some traits have been considered useful for both forensic and
      bioarchaeological applications. One such trait is the arch criterion found in
      subadult ilia, which is defined relative to the greater sciatic notch-auricular
      surface area. In adults, the composite arch has also been described in relation
      to this area and has proven relatively successful in sex determination. This
      study offers an examination of the accuracy of the arch criterion and the
      composite arch in determining the sex of subadult skeletal remains, and an
      assessment of intra- and inter-observer scoring error. A sample of 97 skeletons
      of known sex and age (<15 years) from the Lisbon collection (Portugal) were
      selected and the traits were scored by three observers on orthogonal photos of
      each ilium. In general the agreement within (67.7-88.5%) and between (50.5-76.3%)
      examiners was poor and overall accuracy (26.7-52.6%) did not meet the
      expectations of that reported in previous studies. The authors suggest that this
      derives from great variation in morphology, difficulties in interpreting criteria
      and possibly a lack of association between the expression of the traits and sex.
      Careful examination of sex-related morphology in the immature skeleton and
      additional blind tests of so-called useful traits should continue to be carried
      out.

PMID- 18343615
TI  - Methotrexate as single therapy in Crohn's disease: is its long-term efficacy
      limited?
AB  - OBJECTIVE: To determine the efficacy and patient tolerance of parenteral
      methotrexate in the treatment of Crohn's disease at a dose of 25mg per week for
      three months, then at 15-25mg per week as maintenance therapy. PATIENTS AND
      METHODS: Thirty-five patients (27 women, eight men; mean age 36 years) with
      steroid-dependent Crohn's disease were included in the study after failure of
      azathioprine in 34 cases. Clinical remission was defined as a Harvey-Bradshaw
      disease-activity index less than or equal to 4 and complete weaning from
      steroids. RESULTS: At the end of the three-month induction treatment, the Harvey
      Bradshaw index decreased significantly (4.6+/-2.9 versus 9.4+/-5.2; P=0.0001), as
      did serum CRP (24+/-27 versus 43+/-45 mg/L; P=0.01) and prednisone dose (5.63+/
      7.3 versus 21.1+/-18.7 mg/L; P=0.00001). The mean maintenance dose of
      methotrexate was 20.3+/-3.8 mg per week. The rate of clinical remission was 50%
      at three months and 28% at one year and two years. Nine patients had an adverse
      event attributed to methotrexate that led to drug withdrawal in six cases (17%).
      CONCLUSION: Our findings suggest that, for steroid-dependent Crohn's disease
      which has failed to respond to thiopurines, long-term methotrexate remains
      effective in fewer than one in three patients.

PMID- 18343616
TI  - [Unusual tumor of the stomach].
AB  - Stomach melanomas are exceptional and often secondary to cutaneous tumors. Their
      symptomatology is not specific. We report the case of a 66-year-old woman,
      hospitalized with a three month history of epigastric pain and weight loss.
      Gastroscopy had revealed a polyp of the gastric mucosa. Histopathologic
      examination confirmed the diagnosis of a gastric infiltration by a melanoma. At
      exploration, there were lung, liver and bone metastasis and no cutaneous
      melanoma. The diagnosis of polymetastasis from a melanoma without primitive was
      kept. The patient died three months later.

PMID- 18343617
TI  - Bone marrow edema and bone bruising are now well recognised concepts amongst
      radiologists. Foreword.

PMID- 18343618
TI  - Development of a liquid chromatography method for the analysis of josamycin.
AB  - Out of three methods for the analysis of josamycin, the best one was selected and
      used as starting point for further development. A central composite design was
      applied to find the most influencing parameters and to optimize the
      chromatographic conditions and a full factorial design was used to perform a
      robustness study. The final method uses a Hypersil ODS column 5microm,
      250mmx4.6mm i.d. maintained at 45 degrees C. The mobile phase is composed of
      acetonitrile-phosphate buffer (pH 3, 0.2moll(-1))-tetrabutylammonium hydrogen
      sulphate 0.2moll(-1)-water (21:5:3:71, v/v/v/v). Strongly retained impurities
      after the main peak require gradient elution, which is obtained by increasing
      linearly the acetonitrile concentration (from 21% to 50%, v/v) and decreasing the
      TBA concentration (from 3% to 0%, v/v) in the mobile phase. The total run time
      was 65min. UV detection is performed at 232nm and the flow rate is 1ml/min. The
      method shows good selectivity, precision, linearity and sensitivity. Five
      commercial bulk samples were analyzed.

PMID- 18343619
TI  - Analytical methodologies for the determination of cisplatin.
AB  - cis-Diamminedichloroplatinum(II) (cisplatin) is a important chemotherapeutic drug
      for cancer treatment since 1978. Unfortunately, because of the severe side
      effects like nephrotoxicity, ototoxicity, etc., they are administered in small
      doses at low concentration establishing the maximum limit dosage to 100 mg/m(2)
      (21 days). A variety of analytical methods have been proposed for the
      determination of cisplatin in biological fluids and tissues that permit the
      accurate determination at or below the part per billion level in the native
      sample. The purpose of the current review is to provide a systematic survey of
      the latest analytical techniques for the determination of cisplatin in biological
      samples.

PMID- 18343620
TI  - Preparative enantiomeric separation of potent AMP-activated protein kinase
      activator by HPLC on amylose-based chiral stationary phase. Determination of
      enantiomeric purity and assignment of absolute configuration.
AB  - The development of high performance liquid chromatography method on amylose-based
      stationary phases (Chiralpak AD) has permitted to achieve the preparative
      enantioseparation of one benzimidazole derivative, potent-AMP-kinase (AMPK)
      activator with satisfactory yields. Analytical enantioseparation method was
      optimized and validated to determine the enantiomeric purity. Using the UV
      detection, repeatability, limits of detection (LD) and quantification (LQ) were
      determined. Single-crystal X-ray analysis was successful to determine the
      absolute configuration of the individual enantiomers. A relation between the
      retention order and the absolute configuration of the enantiomers was
      established.

PMID- 18343621
TI  - Enantioseparations related to pharmaceutical and biomedical analysis. Preface.

PMID- 18343622
TI  - Quantitative detection of metallo-beta-lactamase of blaIMP-cluster-producing
      Pseudomonas aeruginosa by real-time polymerase chain reaction with melting curve
      analysis for rapid diagnosis and treatment of nosocomial infection.
AB  - In this study, we established the rapid quantitative detection of metallo-beta
      lactamase-producing Pseudomonas aeruginosa in clinical isolates and samples using
      real-time polymerase chain reaction (PCR) targeting gyrB (identification of P.
      aeruginosa) and blaIMP. The relative sensitivities and specificities of this real
      time PCR assay were as follows: 100.0% and 100.0% for clinical isolates, and
      100.0% and 98.4% for clinical specimens, respectively. The relative sensitivities
      and specificities of blaIMP-PCR were 100.0% in both clinical isolates and
      clinical specimens. The present PCR assay was easily and quickly performed, and
      it accurately detected P. aeruginosa and metallo-beta-lactamase.

PMID- 18343623
TI  - Health educators' perceptions of a sexual health intervention for homeless
      adolescents.
AB  - OBJECTIVE: The purpose of this qualitative descriptive study was to explore the
      perceptions and experiences of health educators in providing a brief, street
      based intervention to homeless adolescents. METHOD: Qualitative data were
      collected via e-mail from a purposive sample of 13 male and female health
      educators who provided the intervention and analyzed using manifest and latent
      content analysis techniques. RESULTS: Five categories with two or more
      subcategories were identified in the data and included how the educators' views
      changed, how they felt homeless youth were similar to and different from other
      adolescents, positive aspects and challenges of providing the intervention, and
      suggestions for future interventionists working with this population.
      CONCLUSIONS: The health educators' practice was strengthened over the course of
      providing the intervention through their positive experiences, changes in their
      perceptions, some of which were biased, and ability to confront the challenges
      that accompany working with this vulnerable population. PRACTICE IMPLICATIONS:
      Health educators who work with this population should learn about the culture of
      homeless youth and characteristics of homeless youth that may influence their
      participation in a sexual health intervention. Moreover, they need to be non
      judgmental, practice the intervention, be aware of their biases, and remain
      flexible.

PMID- 18343624
TI  - Discussion of alternatives, risks and benefits in pediatric acute care.
AB  - OBJECTIVE: Across adult healthcare, discussions of alternatives, risks and
      benefits vary in inclusiveness or are even absent. We examine these discussions
      and their associated factors in pediatric visits. METHODS: Coders noted speaker
      and recipient for alternatives, risks and benefits from 98 videotaped visits.
      Outcomes included discussion of alternatives, risks or benefits (yes/no) and
      involvement of parent or child in discussions (active or passive). Bivariate
      techniques were used to relate visit factors to outcomes. RESULTS: Most visits
      included discussion of alternatives (58% of visits), risks (54%) and benefits
      (69%). Longer visits were more likely to include risk discussions. For
      alternatives, active parent/child involvement was more likely with college
      graduate parents; for risks active involvement was more likely with female and
      more experienced physicians. Parents and children raised risks more frequently
      than benefits, often focusing on disadvantages such as taste or
      frequency/duration of therapy. CONCLUSION: Most pediatric visits include
      alternatives, risks and benefits but parent/child involvement in raising these
      topics is limited. PRACTICE IMPLICATIONS: When parents or children initiate these
      discussions, they often mention risks salient to adherence. Future work could
      explore whether longer visits or interventions targeted for specific participants
      could foster such discussions.

PMID- 18343625
TI  - Visfatin expression is not associated with adipose tissue abundance in the
      porcine model.
AB  - Visfatin was recently identified as a novel adipokine highly enriched in visceral
      adipose tissue and suggested to play a role in the pathophysiology of obesity and
      type 2 diabetes mellitus. However, the biological role of visfatin remains
      elusive since subsequent studies failed to repeat some of the original findings.
      We report here the cloning of six porcine visfatin transcript variants, resulting
      from alternate polyadenylation or alternate splicing of exons. It is further
      demonstrated that the porcine visfatin gene and protein expression measured in
      fat tissues correlate negatively with subcutaneous (s.c.), visceral and total
      body fat tissue weights. Moreover, there was no correlation between visfatin mRNA
      or protein levels and fasting glucose or insulin. No correlation could be found
      between circulating visfatin and any of the carcass and metabolic parameters. Our
      results also demonstrate that the tumor necrosis factor (TNF)alpha increases
      porcine visfatin gene expression in stromal-vascular (SV) cell cultures, thus
      suggesting an intermediary role for TNFalpha in visfatin response. In conclusion,
      our results demonstrate that the porcine visfatin gene cannot be considered as a
      marker of fat accumulation since the highest visfatin expression levels were
      associated with the leaner animals.

PMID- 18343626
TI  - [Obstructive sleep apnoea syndrome in children].

PMID- 18343627
TI  - The PPARgamma agonist FMOC-L-leucine protects both mature and immature brain.
AB  - (N-[9-fluorenylmethoxycarbonyl]-)-L-leucine (FMOC-L-leucine) and rosiglitazone,
      two ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), were
      evaluated in mature (adult mice) and immature (pups) brain injury models. In
      adult magnesium-deficient mice, a model responsive to both neuroprotective and
      anti-seizure compounds, FMOC-L-leucine, but not rosiglitazone, protected against
      audiogenic seizures. The protection afforded by FMOC-L-leucine was alleviated by
      the PPARgamma antagonist GW9662 (1-2 mg/kg) and was induced in 50% animals by
      4.8+/-1.2 mg/kg. At this dose, FMOC-L-leucine modified audiogenic seizure phase
      durations in convulsing mice differently than prototype antiepileptic drugs did.
      FMOC-L-leucine (up to 100 mg/kg) was inactive in the 6 Hz seizure test, an adult
      animal model largely responsive to anti-seizure drugs. In a model of neonatal
      brain injury, FMOC-L-leucine (4 microg/kg) was neuroprotective against cerebral
      ibotenate toxicity. It reduced significantly the size of lesions in grey but not
      in white matter, while rosiglitazone (10 microg/kg) was inactive. Taken as a
      whole, the present data support neuroprotective potentialities of FMOC-L-leucine
      towards both mature and immature brain. The PPAR-based protection of immature
      brain is more important as it is known that classic adult brain protectants
      (GABA(A) activators, N-methyl-D-aspartate and sodium channel blockers) may be
      toxic for immature brain. The PPARgamma agonist FMOC-L-leucine is likely to be
      devoid of these classic protective mechanisms because of its inactivity in the 6
      Hz seizure test, its activity in the audiogenic test being explained by
      neuroprotective rather than intrinsic anti-seizure mechanisms. Targeting PPARs
      might be thus a promising way to protect immature brain.

PMID- 18343628
TI  - A pioneer study on the anti-ulcer activities of copper nicotinate complex [CuCl
      (HNA)2] in experimental gastric ulcer induced by aspirin-pylorus [corrected]
      ligation model (Shay model).
AB  - This study was planned to look for a more rational mechanism(s) that could
      explain the anti-ulcer activity of copper nicotinate complex, since the mechanism
      whereby it prevents ulceration still to be investigated. Ulcer and the preventive
      indexes were scored, mucin, juice volume, total acidity, luminal haemoglobin,
      total peroxide and total antioxidant as an oxidative stress index (OSI), as well
      as total DNA fragmentation (as an apoptotic marker) and its percentage ratio in
      the juice were evaluated. Results confirmed the antisecretory ability of copper
      nicotinate, as reflected from the significant reduction of gastric juice volume
      and acid output. Data confirmed also copper nicotinate has a gastrocytoprotective
      action against ulcer pathogenesis through; enhancement of mucin secretion,
      reduction each of ulcer index and the mucosal bleeding rate into the gastric
      lumen; antioxidant activity through scavenging reactive oxygen species (ROS);
      anti-apoptotic activity through attenuation of the DNA fragmentation in the
      ulcerous treated group when compared with each of control and aspirin ulcerous
      untreated groups. This study hypothesized; at least in part, aspirin in the
      acidic environment of gastric juice become un-ionized and freely penetrate the
      mucosal barrier reaching to gastric wall. Due to the weak basic nature of
      cytoplasm of gastric mucosal cells, it accumulates in high concentrations into
      mucosal cells, and yields a negatively charged anion that is unable to exit the
      cell. Thus, superficial or deeper erosions are produced and bleeding takes place,
      within minutes.

PMID- 18343629
TI  - Up-regulation of Toll-like receptor 4 was suppressed by emodin and baicalin in
      the setting of acute pancreatitis.
AB  - Acute pancreatitis (AP) activates the systemic inflammatory response and is
      potentially lethal. Recent studies demonstrated that pancreatic enzymes could
      induce cytokine expression via Toll-like receptor 4 (TLR4) signal pathway,
      indicating a possible role of TLR4 in local pancreatic injury and systemic
      inflammatory response. Emodin, an anthraquinone derivative from Radix et Rhizoma
      Rhei, and baicalin, a flavone from Scutellaria baicalensis Georgi, both have been
      reported to possess anti-inflammatory activities. In present study, we
      investigated the combined effect of emodin and baicalin on pancreatic damage and
      pancreatitis associated lung injury, as well as tissue TLR4 expression in the
      setting of AP. The results showed that combination of emodin and baicalin
      significantly reduced serum amylase, tumor necrosis factor-alpha and interleukin
      6, attenuated pancreatic and pulmonary damage, also suppressed TLR4 expression in
      pancreas and lung. It could be speculated that amelioration of pancreatic and
      pulmonary damage by emodin and baicalin might contribute, in part at least, to
      the suppression of TLR4 expression. The present study provides beneficial
      evidence as to simultaneous treatment for AP, and also suggests an important role
      of TLR4 in pathophysiology of AP.

PMID- 18343630
TI  - The use of fluorescence for detecting MeHg-induced ROS in cell cultures.
AB  - The effect of methylmercury (MeHg) on reactive oxygen species (ROS) induction in
      neural cell lines was measured by the fluorescent probe, chloro methyl derivative
      of di-chloro di-hydro fluoresceindiacetate (CMH2DCFDA). Three different MeHg
      concentrations (5, 10 and 25 microM) and time periods (30, 50 and 90 min) were
      studied in C6-glial and B35-neuronal cell lines. In addition, the relationship
      between MeHg-induced ROS and cell density (day 3 vs. day 4) was also explored.
      The 14C-labelled MeHg measurements were done to determine the cell associated
      MeHg content. At 30 and 50 min exposure, a significant increase (p<0.05) in MeHg
      induced ROS was observed at 10 and 25 microM MeHg for C6 cells and at 25 microM
      MeHg for B35 cells. However, the amount of ROS produced with 25 microM MeHg
      varied significantly (p<0.001) at different time periods. For both the cell
      lines, significant cell density dependent differences (p<0.05) were observed at
      10 microM MeHg treatment for 50 min. MeHg treatments were associated with a
      concentration as well as cell-density dependent increase in cell associated-MeHg.
      These findings provide experimental evidence that special attention should be
      focused upon concentration, exposure time and cell density when assessing MeHg
      induced ROS via fluorescence.

PMID- 18343631
TI  - The effect of disgust on anxiety ratings to fear-relevant, disgust-relevant and
      fear-irrelevant stimuli.
AB  - This study investigated the effect of an experimental disgust induction and
      experience of a homophone spelling task on subsequent anxiety to fear-relevant,
      disgust-relevant and fear-irrelevant stimuli in a non-clinical population. The
      design of the study allowed an assessment of (1) whether disgust facilitates
      anxiety only if the stimulus being evaluated is disgust-relevant and (2) whether
      experiencing the threat-interpretation bias induced by disgust facilitates
      anxiety generally. The results indicated that a disgust induction facilitated
      levels of self-reported anxiety to a range of scenarios regardless of whether
      they were disgust-relevant, fear-relevant or fear-irrelevant, and regardless of
      whether participants had experienced the disgust-induced threat-interpretation
      bias. This study provides evidence for a general effect of disgust on self
      reported anxiety to stimuli regardless of the disgust-relevance or fear-relevance
      of those stimuli. The results lend support to the view that disgust has a causal
      effect on anxiety, and implicates disgust as a risk factor for anxious
      psychopathology.

PMID- 18343632
TI  - Genomic expression patterns distinguish long-term from short-term glioblastoma
      survivors: a preliminary feasibility study.
AB  - We used microarray analysis to investigate associations between genotypic
      expression profiles and survival phenotypes in patients with primary glioblastoma
      (GBM). Tumor samples from 7 long-term glioblastoma survivors (>24 months) and 13
      short-term survivors (<9 months) were analyzed to detect differential patterns of
      gene expression between these groups and to identify genotypic subclasses of
      glioblastomas that correlate with survival phenotypes. Five unsupervised and
      three supervised clustering algorithms consistently and accurately grouped the
      tumors into genotypic subgroups corresponding to the two clinical survival
      phenotypes. Three unique prospective mathematical classification algorithms were
      subsequently trained to use expression data to stratify unknown glioblastomas
      between survival groups and performed this task with 100% accuracy in validation
      studies. A set of 1478 genes with significant differential expression (p<0.01)
      between long-term and short-term survivors was identified, and additional
      mathematical filtering was used to isolate a 43-gene "fingerprint" that
      distinguished survival phenotypes. Differential regulation of a subset of these
      genes was confirmed using RT-PCR. Gene ontology analysis of the fingerprint
      demonstrated pathophysiologic functions for the gene products that are consistent
      with current models of tumor biology, suggesting that differential expression of
      these genes may contribute etiologically to the observed differences in survival.
      These results demonstrate that unique expression profiles characterize genotypic
      subsets of primary GBMs associated with differential survival phenotypes, and
      these profiles can be used in a prospective fashion to assign unknown tumors to
      survival groups. Future efforts will focus on building more robust classifiers
      and identifying additional subclasses of gliomas with phenotypic significance.

PMID- 18343633
TI  - Alterations in myocardial gene expression associated with experimental
      Trypanosoma cruzi infection.
AB  - Chagas disease, characterized by acute myocarditis and chronic cardiomyopathy, is
      caused by infection with the protozoan parasite Trypanosoma cruzi. We sought to
      identify genes altered during the development of parasite-induced cardiomyopathy.
      Microarrays containing 27,400 sequence-verified mouse cDNAs were used to analyze
      global gene expression changes in the myocardium of a murine model of chagasic
      cardiomyopathy. Changes in gene expression were determined as the acute stage of
      infection developed into the chronic stage. This analysis was performed on the
      hearts of male CD-1 mice infected with trypomastigotes of T. cruzi (Brazil
      strain). At each interval we compared infected and uninfected mice and confirmed
      the microarray data with dye reversal. We identified eight distinct categories of
      mRNAs that were differentially regulated during infection and identified
      dysregulation of several key genes. These data may provide insight into the
      pathogenesis of chagasic cardiomyopathy and provide new targets for intervention.

PMID- 18343634
TI  - An interactive dynamic analysis and decision support software for MR mammography.
AB  - A fully automated software is introduced to facilitate MR mammography (MRM)
      examinations and overcome subjectiveness in diagnosis using normalized maximum
      intensity-time ratio (nMITR) maps. These maps inherently suppress enhancements
      due to normal parenchyma and blood vessels that surround lesions and have natural
      tolerance to small field inhomogeneities and motion artifacts. The classifier
      embedded within the software is trained with normalized complexity and maximum
      nMITR of 22 lesions and tested with the features of remaining 22 lesions.
      Achieved diagnostic performances are 92% sensitivity, 90% specificity, 91%
      accuracy, 92% positive predictive value and 90% negative predictive value.
      DynaMammoAnalyst shortens evaluation time considerably and reduces inter and
      intra-observer variability by providing decision support.

PMID- 18343635
TI  - A computational method for the estimation of atrophic changes in Alzheimer's
      disease and mild cognitive impairment.
AB  - Early diagnosis and objective monitoring of disease progression are essential for
      the development of therapeutic strategies in Alzheimer's disease (AD). Current
      techniques are mainly based on semi-objective measures such as neuropsychological
      tests and a physician's magnetic resonance imaging (MRI) inspection. We have
      developed a computational method for automatic and unbiased assessment of the
      brain's state of atrophy from MRI. Sixty-eight high-resolution MRI scans were
      acquired from 25 AD patients (age: 69.8+/-7.5), 16 mild cognitive impairment
      (MCI) patients (67.6+/-9.1) and 27 control subjects (64.9+/-8.8). On the basis of
      the computations we were able to recognize MCI subjects with a sensitivity of 81%
      and a specificity of 80% in a group of MCIs and controls using a linear
      classifier. To date, comparable results have only been received by manual
      labelling or human inspection. Our calculations are light weighted and can be
      applied on usual workstations in everyday clinical practice. Each step can be
      understood and applied by the physicians, independent of their computer
      knowledge. The applied image analysis process produces visual maps of atrophic
      changes as intermediate steps of the calculations. These can be helpful for the
      physician during inspection of the brain. The proposed analysis has the potential
      to improve AD diagnosis and treatment, especially in early its stages, and could
      also be used to monitor disease progression in therapeutic trials.

PMID- 18343636
TI  - Effect of a hypocaloric diet on serum visfatin in obese non-diabetic patients.
AB  - OBJECTIVE: Obesity and insulin resistance are associated with classic and new
      cardiovascular risk factors, such as inflammatory markers and adipocytokines. The
      aim of this study was to examine whether weight reduction could change visfatin
      serum concentrations in obese patients. METHODS: This was an interventional
      longitudinal study analyzing a population of 80 obese non-diabetic outpatients.
      Weight, blood pressure, fasting serum glucose, C-reactive protein, plasma
      insulin, total cholesterol, low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, triacylglycerols, and insulin resistance (homeostatic
      model assessment) were measured before and after 3 mo on a hypocaloric diet.
      RESULTS: Eighty patients were enrolled. The mean age was 46.7 +/- 16.7 y, the
      mean body mass index was 34.1 +/- 4.8 kg/m(2), with 20 men (25%) and 60 women
      (75%). After 3 mo on a hypocaloric diet, body mass index, fat mass, waist
      circumference, systolic blood pressure, fasting serum glucose, total cholesterol,
      and low-density lipoprotein cholesterol decreased. The serum concentration of
      visfatin decreased with weight loss (112.14 +/- 70.2 versus 99.4 +/- 58.1 ng/mL,
      P < 0.05). In the multivariate analysis of visfatin concentration before and
      after treatment, as a dependent variable, only age remained an independent
      predictor in the model (F = 12.5, P < 0.02), with an inverse correlation:
      visfatin decreased 4.1 g/mL (F = 12.5, P < 0.05) and 3.7 g/mL (95% confidence
      interval 1.2-6.1), respectively, for each year of age. CONCLUSION: Weight
      reduction after a 3-mo period of a hypocaloric diet is associated with a
      significant decrease in circulating serum concentrations of the novel adipokine
      visfatin in obese subjects. Visfatin is inversely correlated with age.

PMID- 18343637
TI  - Modulation of Helicobacter pylori colonization with cranberry juice and
      Lactobacillus johnsonii La1 in children.
AB  - OBJECTIVE: Probiotics and cranberry have been shown to inhibit Helicobacter
      pylori in vitro owing to bacteriocin production and high levels of
      proanthocyanidins, respectively. These effects have been confirmed in clinical
      trials with H. pylori-positive subjects. The aim of this study was to evaluate
      whether regular intake of cranberry juice and the probiotic Lactobacillus
      johnsonii La1 (La1) may result in an additive or synergistic inhibition of H.
      pylori in colonized children. METHODS: A multicentric, randomized, controlled,
      double-blind trial was carried out in 295 asymptomatic children (6-16 y of age)
      who tested positive for H. pylori by (13)C-urea breath test (UBT). Subjects were
      allocated in four groups: cranberry juice/La1 (CB/La1), placebo juice/La1 (La1),
      cranberry juice/heat-killed La1 (CB), and placebo juice/heat-killed La1
      (control). Cranberry juice (200 mL) and La1 product (80 mL) were given daily for
      3 wk, after which a second UBT was carried out. A third UBT was done after a 1-mo
      washout in those children who tested negative in the second UBT. RESULTS: Two
      hundred seventy-one children completed the treatment period (dropout 8.1%).
      Helicobacter pylori eradication rates significantly differed in the four groups:
      1.5% in the control group compared with 14.9%, 16.9%, and 22.9% in the La1, CB,
      and CB/La1 groups, respectively (P < 0.01); the latter group showed a slight but
      not significant increase when compared with the other treated groups. The third
      UBT was carried out only in 19 of the 38 children who tested negative in the
      second UBT and H. pylori was detected in 80% of them. CONCLUSION: These results
      suggest that regular intake of cranberry juice or La1 may be useful in the
      management of asymptomatic children colonized by H. pylori; however, no
      synergistic inhibitory effects on H. pylori colonization were observed when both
      foodstuffs were simultaneously consumed.

PMID- 18343638
TI  - Downregulation of hepatic lipoprotein assembly in rats by fermented products of
      Monascus pilosus.
AB  - OBJECTIVE: Hypercholesterolemia is a major risk factor for atherosclerosis. The
      fermented products of Monascus sp. have been known for their
      antihypercholesterolemic effect; however, the studies mostly have focused on the
      inhibition of cholesterol biosynthesis in liver. In this study, we examined
      whether fermented products of Monascus pilosus have regulatory effects on the
      hepatic lipoprotein assembly. METHODS: Male Wistar rats were fed 1% cholesterol
      diet for 2 wk. After hypercholesterolemia was induced, the animals were
      maintained on this cholesterol diet supplemented with M. pilosus-fermented
      products grown in regular medium/garlic-containing medium or garlic powder for
      another 6 wk. The concentration of blood lipids and the expression of proteins
      involved in lipoprotein assembly and hepatic antioxidation were assayed. RESULTS:
      Maintenance on a 1% cholesterol diet for 2 wk significantly (P < 0.05) raised
      animals' blood lipid levels and increased the expression of intestinal microsomal
      triacylglycerol transfer protein, hepatic apolipoprotein B-100, and acyl-coenzyme
      A:cholesterol acyltransferase. Supplementation of M. pilosus-fermented products
      or garlic powder significantly (P < 0.05) lowered animals' blood lipid levels and
      inhibited the expression of intestinal microsomal triacylglycerol transfer
      protein and hepatic apolipoprotein B-100. The 3-hydroxy-3-methylglutaryl-coenzyme
      A reductase was downregulated by the M. pilosus-fermented product grown in
      regular medium but not in garlic-containing medium. The expression of antioxidant
      enzymes was significantly upregulated by the M. pilosus-fermented product grown
      in garlic-containing medium. CONCLUSION: Monascus sp.-fermented products exert
      the hypocholesterolemic effect by mechanisms other than the inhibition of
      cholesterol biosynthesis.

PMID- 18343639
TI  - Validation of a food frequency questionnaire for assessing dietary nutrients in
      Brazilian children 5 to 10 years of age.
AB  - OBJECTIVE: This study aimed to assess the relative validity of a food frequency
      questionnaire (FFQ), previously validated to measure usual intakes in adults, for
      measuring dietary intakes in children 5 to 10 y of age. METHODS: Dietary intakes
      were measured using an FFQ and a 3-d dietary record. Healthy children, 5 to 10 y
      old (n = 151), were recruited from public schools and asked to answer the
      questions in the FFQ and to provide non-consecutive 3-d dietary records based on
      reported estimated portion sizes. Paired sample t tests and Pearson's correlation
      coefficients were conducted to determine whether the two instruments reported
      similar values for energy and nutrients. The agreement of quartile categorization
      between the two instruments was also examined. RESULTS: Estimated energy and
      nutrient intakes derived from the FFQ were significantly higher than those
      derived from 3-d dietary records. As expected, Pearson's correlations increased
      after adjusting for residual measurement error, presumably due to exclusion of
      the high within-person variability in intake of these nutrients. Moderate to high
      (r > 0.50) correlation coefficients were verified for some nutrients such as
      calcium, folate, vitamin B2, vitamin A, and vitamin C. CONCLUSION: This FFQ,
      originally developed for use in adults, appears to overestimate usual energy and
      nutrient intakes in children 5 to 10 y of age. Further work is necessary to
      conduct a calibration study to establish adequate portion sizes before instrument
      adoption in this population.

PMID- 18343640
TI  - Demonstration of intrinsic efflux activity of Escherichia coli K-12 AG100 by an
      automated ethidium bromide method.
AB  - Demonstration of efflux of ethidium bromide (EtBr) has been made for over 30
      bacterial species, usually by showing enhanced efflux in multidrug-resistant
      strains that was then abolished by inactivating efflux pumps. Here we present a
      relatively simple automated method that employs EtBr as an efflux pump substrate
      for the demonstration of intrinsic efflux activity in Escherichia coli K-12
      AG100. The method uses the Rotor-Gene 3000 instrument for real-time fluorometric
      measurement of EtBr accumulation under conditions that limit energy (absence of
      glucose, low temperature) and of EtBr extrusion under optimum conditions. The
      method can be used for screening compound libraries for efflux inhibiting
      capacity.

PMID- 18343641
TI  - A controlled intervention study to improve antibiotic use in a Russian paediatric
      hospital.
AB  - A controlled intervention study was performed in a paediatric hospital in Russia
      to improve antibiotic use and to see whether improvements persisted. During
      October-December 2002, clinical and microbiological data, antibiotic use, costs
      and outcome were recorded at two wards for gastrointestinal infections (GIIs) and
      two wards for respiratory tract infections (RTIs). Guidelines for diagnosis and
      treatment of infections were developed and implemented at one ward for GIIs and
      one ward for RTIs in 2003. The other two wards served as controls. The same data
      were recorded during the same 3-month periods in 2003 and 2004. At the
      intervention ward, the percentage of patients with GII who received antibiotics
      decreased from 94% in 2002 to 41% in 2003, but increased to 73% in 2004. In RTI
      patients these percentages were 90% in 2002, 53% in 2003 and 83% in 2004. The
      proportions of patients who received antibiotics in 2004 were still lower than in
      2002: risk difference (RD)=0.217 (P</=0.001) in GIIs and RD=0.073 (P=0.013) in
      RTIs. From 2002 to 2004 there was a decrease in cephalosporin use (P=0.021) and
      an increase in penicillin use (P=0.032) in pneumonia. There was no difference in
      mortality, duration of fever or duration of hospital stay between the
      intervention and control wards. Antibiotic use could be halved without
      compromising the quality of patient care, but 1 year after the intervention the
      use of antibiotics approached pre-intervention levels. Strategies to sustain the
      effect of interventions are needed.

PMID- 18343642
TI  - Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in
      mediating the ghrelin-induced locomotor stimulation and dopamine overflow in
      nucleus accumbens.
AB  - Previously, we have reported that the orexigenic peptide ghrelin activates the
      cholinergic-dopaminergic reward link, involving nicotinic acetylcholine receptors
      (nAChR). The alpha(3)-alpha(7) and beta(2)-beta(4) subunits of the nAChR can be
      combined into pentameric nAChRs, with different functional roles. The present
      experiments show that the locomotor stimulatory effects of ghrelin, either into
      laterodorsal tegmental area (LDTg) or ventral tegmental area (VTA), are mediated
      via ventral tegmental nAChR, but neither the alpha(4)beta(2) (using dihydro-beta
      erythroidine) nor the alpha(7) (using methyllycaconitine) subtypes appears to be
      involved. On the other hand, the alpha(3)beta(2), beta(3) and/or alpha(6) (using
      alpha-conotoxin MII) subtypes in the VTA mediate the stimulatory and DA-enhancing
      effects of ghrelin, a pattern that ghrelin shares with ethanol (n=5-8).
      Radioligand-binding experiments shown that ghrelin does not interfere directly
      with nAChRs (n=26). We therefore suggest that the alpha(3)beta(2), beta(3) and/or
      alpha(6) subtypes might be pharmacological targets for treatment of addictive
      behaviours including compulsive overeating and alcoholism.

PMID- 18343643
TI  - TGFbeta1 and TGFbeta3 are partially redundant effectors in brain vascular
      morphogenesis.
AB  - Gene deletion experiments have shown that the three TGFbeta isoforms regulate
      distinct developmental processes. Recent work by our group and others showed that
      the integrins alphavbeta6 and alphavbeta8 activate latent forms of TGFbeta1 and
      TGFbeta3. This raises the possibility that TGFbeta1 and TGFbeta3 act redundantly
      in developmental processes where both isoforms are expressed and activation is by
      integrins. To investigate this issue, we generated mice with defective integrin
      mediated TGFbeta1 activation (Tgfb1(RGE/RGE)) that were also homozygous for a
      null mutation in the TGFbeta3 gene. Tgfb1(RGE/RGE); Tgfb3(-/-) mice have severely
      perturbed development of the brain vasculature that is highly similar to that in
      mice lacking alphavbeta8. Some Tgfb1(RGE/RGE); Tgfb3(+/-) and Tgfb1(RGE/RGE);
      Tgfb3(+/+) mice have milder, background-dependent versions of the phenotype. In
      addition, we found that Tgfb3 gene status influences embryonic lethality due to
      TGFbeta1 deficiency after limited backcrossing to the BALB/c background.
      Conversely, Tgfb1 gene status modifies the extent of palate fusion in Tgfb3(-/-)
      mice after limited backcrossing to the ICR background. Our results are consistent
      with a functional connection between TGFbeta1 and TGFbeta3 during development
      based on a shared mechanism of activation.

PMID- 18343644
TI  - Articaine interaction with DSPC bilayer: a 13C and 31P solid-state NMR study.
AB  - Articaine hydrochloride, 4-methyl-3-(2-[propylamino]propionamido)-2
      thiophenecarboxylic acid, methyl ester hydrochloride, is a local anaesthetic
      commonly used in dentistry, and is classified as an amide local anaesthetic.
      Solid-state (13)C and (31)P NMR were used to investigate the uncharged articaine
      species (sample pH 10.0) when interacting with distearoylphosphatidylcholine
      (DSPC) model membranes. The DSPC phospholipid bilayer was studied at four
      different molar ratios of articaine, 10, 25, 40, and 55 mol%, respectively. The
      articaine concentration-dependent decrease in the DSPC bilayer gel-to-liquid
      crystalline phase-transition temperature demonstrates substantial articaine
      interaction with this bilayer. A DSPC bilayer contains a large hydrophobic core
      and the (13)C and (31)P NMR spectra of the 40 mol% articaine-containing sample
      demonstrate a disturbance in the molecular packing of the polar bilayer region
      that extends into the hydrophobic region, evidenced by carbon 2 and 3 of the
      stearoyl acyl chains. Observed (31)P and (13)C NMR spectral changes when
      articaine is increased from 40 to 55 mol%, suggest formation of articaine
      aggregates and decrease in DSPC bilayer perturbation at the latter articaine
      level.

PMID- 18343645
TI  - The cancer reform strategy.

PMID- 18343646
TI  - Tiotropium and salmeterol/fluticasone combination do not cause oxygen
      desaturation in COPD.
AB  - It has been documented that tiotropium is less likely to induce oxygen
      desaturation in stable COPD patients compared to long-acting beta2-agonists
      (LABAs) and combined administration of a LABA and an inhaled corticosteroid (ICS)
      reduces the potential for acute effects of LABA on blood-gas tensions. In this
      study, we have compared the acute effects of tiotropium 18 microg and
      salmeterol/fluticasone combination (SFC) 50/250 microg on arterial blood gases in
      20 patients with stable COPD. Each subject was studied on 2 days, separated from
      one another by at least 4 days. Blood specimens were taken just before the
      inhalation and at 15, 30, 60, 180 and 360 min after inhalation of each treatment,
      and spirometry was performed at the same time points. As expected, both
      treatments significantly improved FEV1 (greatest changes were 0.20 L, 95% CI:
      0.13-0.27 at 360 min after tiotropium; and 0.13 L, 95% CI: 0.06-0.19 at 180 min
      after SFC). The greatest mean changes from baseline in PaO2 were -1.7 (95% CI: 
      4.0 to 0.6)mmHg, p=0.134, after tiotropium; -0.8 (95% CI: -2.2 to 0.6)mmHg, after
      SFC. Both changes were observed after 15 min. Both drugs caused a small decrease
      in PaCO2 (greater changes: -1.9 (95% CI -3.2 to -0.6)mmHg, p=0.005 at 60 min
      after tiotropium; and -2.4 (95% CI: -3.5 to -1.3) mmHg, p=0.0002 at 180 min after
      SFC). These results indicate that both tiotropium and SFC are able to induce a
      significant long-last bronchodilation without affecting arterial blood gases.
      Moreover, they confirm that the impact of tiotropium on PaO2 is small and without
      clinical significance and the addition of a LABA to an ICS can reduce the
      potentially dangerous acute effect of the LABA on blood gases.

PMID- 18343647
TI  - Variation in severity and type of sleep-disordered breathing throughout 4 nights
      in patients with heart failure.
AB  - BACKGROUND: Over 50% of patients with chronic heart failure (CHF) have sleep
      disordered breathing (SDB). Any variation in the type of SDB in CHF will have
      implications for patient management. Currently there is good evidence for
      treatment of obstructive sleep apnea (OSA) in CHF with continuous positive airway
      pressure; however, for central sleep apnea (CSA) the treatment is less clear.
      AIMS: The aim of this study was to investigate the variation in the severity and
      type of SDB (OSA vs. CSA) throughout 4 consecutive nights in CHF patients with
      SDB. METHODS: Nineteen male CHF patients (mean+/-sd: age 61+/-9 years; left
      ventricular ejection fraction: 34+/-10% and percent predicted peak VO2: 67+/-19%)
      underwent cardiorespiratory monitoring in their own home throughout 4 consecutive
      nights. RESULTS: There was minimal variation in apnea-hypopnea index (AHI)
      throughout 4 nights in CHF patients with SDB [intraclass correlation coefficient
      (95% confidence interval (CI)): 0.97 (95% CI 0.76 and 0.97)]. Eight patients [42%
      (95% CI 20% and 64%)] demonstrated a shift in the type of their SDB, from CSA to
      OSA or vice versa; these patients had significantly smaller neck circumference
      (group mean+/-sd) 42+/-2 vs. 44+/-2 cm; p=0.04), and had significant variation in
      the central AHI [intraclass correlation coefficient: 0.51 (95% CI 0.16 and
      0.85)]. CONCLUSIONS: A single night of cardiorespiratory monitoring is
      representative of moderate-to-severe SDB in patients with CHF. However, a high
      proportion of patients shift their type of SDB over 4 nights. These findings may
      have implications for the management of SDB in CHF.

PMID- 18343648
TI  - Vaso-active therapy can improve 6-min walk distance in patients with pulmonary
      hypertension and fibrotic interstitial lung disease.
AB  - BACKGROUND: Dyspnea and functional limitation in interstitial lung diseases (ILD)
      are not always adequately explained by the degree of compromise in pulmonary
      function alone. Pulmonary hypertension (PH) is felt to be a major contributor to
      morbidity and mortality in these patients. It is not clear whether treatment with
      newer vaso-active agents benefits patients with PH in the setting of moderate or
      severe ILD. METHODS: Medical records of patients followed at our institution
      between July 2001 and June 2005 were reviewed to identify patients with moderate
      or severe fibrotic ILD and PH. Data regarding demographics, hemodynamics, and
      clinical characteristics at baseline and during follow-up were collected.
      RESULTS: We identified 19 patients who met our inclusion criteria and in whom
      vaso-active therapy [epoprostenol (N=10), bosentan (N=9)] was initiated. Most
      patients [(15/19(79%)] showed an initial positive response to therapy and
      improved their 6-min walk distance (6MWD) by >50m (responders) and 12/15 (80%)
      improved by at least 1 WHO functional class. At 1-year follow-up, 7 of 15 (47%)
      'responders' had deteriorated significantly. None of the patients died during 1
      year of follow-up. CONCLUSIONS: Epoprostenol and bosentan produced short-term
      functional benefit in our patients with PH and moderate or severe restrictive
      ILD. The generalizability of these results awaits the results of larger,
      prospective, randomized trials in such patients.

PMID- 18343649
TI  - Time to desaturation in the 6-min walking distance test predicts 24-hour oximetry
      in COPD patients with a PO2 between 60 and 70mmHg.
AB  - BACKGROUND: The 6-min walking distance (6MWD) test is a useful tool for assessing
      patients with chronic obstructive pulmonary disease (COPD), but little is known
      about the changes in oxygen saturation that occur during the test. OBJECTIVE: To
      predict the oximetry profile during daily living activities by the time to
      desaturation in the 6MWD test in COPD-affected patients. PATIENTS AND METHODS: We
      studied 67 COPD patients with moderate hypoxemia performing a 6MWD test and a 24
      hour ambulatory pulse oximetry (24-hr PO). We determined the time to desaturation
      (SatO290%) in the 6MWD test, in the daytime, nighttime and 24-hr PO. We then
      estimated the time to desaturation that better predicts desaturation in diurnal,
      nocturnal and 24-hour oximetries using the ROC type II analysis. RESULTS: The
      patients who desaturated after 3'30min have a 100% probability not to desaturate
      during diurnal, nocturnal and 24-hr PO. Those patients who desaturated during the
      first minute of the 6MWD test have a 74% probability to desaturate in these
      oximetries. CONCLUSIONS: The time to desaturation in the 6MWD test can
      discriminate early desaturators who desaturate during their daily living
      activities and late desaturators who do not desaturate. Ambulatory oximetry would
      thus only be necessary in patients with a time to desaturation that ranges
      between 1 and 3'30''.

PMID- 18343650
TI  - Fabrication of bienzyme nanobiocomposite electrode using functionalized carbon
      nanotubes for biosensing applications.
AB  - Mediated biosensors consisting of an oxidase and peroxidase (POx) have attracted
      increasing attention because of their wider applicability. This work presents a
      novel approach to fabricate nanobiocomposite bienzymatic biosensor based on
      functionalized multiwalled carbon nanotubes (MWNTs) with the aim of evaluating
      their ability as sensing elements in amperometric transducers. Electrochemical
      behavior of the bienzymatic nanobiocomposite biosensor is investigated by
      Faradaic impedance spectroscopy and cyclic voltammetry. The results indicate that
      glucose oxidase (GOD) and horseradish peroxidase (HRP) are strongly adsorbed on
      the surface of the thionin (TH) functionalized MWNTs and demonstrate a facile
      electron transfer between immobilized GOD/HRP and the electrode via the
      functionalized MWNTs in a Nafion film. The functionalized carbon nanotubes act as
      molecular wires to allow efficient electron transfer between the underlying
      electrode and the redox centres of enzymes through TH. Linear ranges for these
      electrodes are from 10nM to 10mM for glucose and 17nM to 56mM for hydrogen
      peroxide with the detection limit of 3 and 6nM, respectively. A remarkable
      feature of the bienzyme electrode is the possibility to determine glucose and
      hydrogen peroxide at a very low applied potential where the noise level and
      interferences from other electroactive compounds are minimal. Performance of the
      biosensor is evaluated with respect to response time, detection limit,
      selectivity, temperature and pH as well as operating and storage stability.

PMID- 18343651
TI  - Neural mechanisms underlying sex-specific behaviors in vertebrates.
AB  - From invertebrates to humans, males and females of a given species display
      identifiable differences in behaviors, mostly but not exclusively pertaining to
      sexual and social behaviors. Within a species, individuals preferentially exhibit
      the set of behaviors that is typical of their sex. These behaviors include a wide
      range of coordinated and genetically pre-programmed social and sexual displays
      that ensure successful reproductive strategies and the survival of the species.
      What are the mechanisms underlying sex-specific brain function? Although sexually
      dimorphic behaviors represent the most extreme examples of behavioral variability
      within a species, the basic principles underlying the sex specificity of brain
      activity are largely unknown. Moreover, with few exceptions, the quest for
      fundamental differences in male and female brain structures and circuits that
      would parallel that of sexual behaviors and peripheral organs has so far
      uncovered modest quantitative rather than the expected clear qualitative
      differences. As will be detailed in this review, recent advances have directly
      challenged the established notion of the unique role of steroid hormones in
      organizing and activating male- and female-specific brain circuits and have
      uncovered new mechanisms underlying the neural control of sex-specific behaviors.

PMID- 18343652
TI  - Prevention of anaemia by early intervention with once weekly epoetin alfa during
      chemotherapy.
AB  - This study compared the effects of early intervention with standard use of
      epoetin alfa on haemoglobin (Hb) levels and transfusion requirements in cancer
      patients receiving chemotherapy. Patients with Hb>10 and < or= 12 g/dL were
      randomised 1:1 to epoetin alfa (40,000 IU, subcutaneously, once weekly),
      initiated within 7d of the start of the first on-study chemotherapy cycle
      (defined as early intervention) versus epoetin alfa when Hb <or= 10 g/dL (defined
      as standard therapy). Increases in Hb values were significantly higher with early
      intervention compared to standard therapy from week 6 to 10 (P <or= 0.05) and
      approached significance at week 15/16 (P=0.0531). Although the percentage of
      patients receiving blood transfusions was similar in both groups, the amount of
      blood transfused was almost twice as high in the standard epoetin alfa group
      (n.s.). Early intervention with epoetin alfa was well tolerated and overall
      survival did not differ significantly between groups. Initiation of epoetin alfa
      at the onset of chemotherapy and Hb<12 g/dL improves Hb levels significantly
      versus standard therapy.

PMID- 18343653
TI  - Cancer screening: evidence and practice in Europe 2008.
AB  - We examine the theoretical basis of screening, followed by an evaluation of
      screening initiatives from a population health perspective and a discussion of
      the organisation of mass screening programmes. Evidence for the effectiveness of
      screening by primary site from both randomised trials and evaluation of service
      screening is summarised and the existing cancer screening programmes in the
      European Union are described. Sufficient evidence from several randomised trials
      to demonstrate mortality reduction exists for breast cancer and colorectal cancer
      screening. At least one trial has shown efficacy with a mortality end-point in
      screening for hepatocellular carcinoma and oral cancer. Randomised trials have
      demonstrated a lack of mortality effect in lung cancer screening based on chest X
      ray and sputum cytology. Despite the lack of randomised trials, population
      screening for cervical cancer with cytological smears has been convincingly shown
      to reduce cervical cancer incidence and mortality.

PMID- 18343654
TI  - Evaluation of the cancer chemopreventive efficacy of silibinin in genetic mouse
      models of prostate and intestinal carcinogenesis: relationship with silibinin
      levels.
AB  - Silibinin, a flavonolignan from milk thistle seeds, possesses cancer
      chemopreventive properties in rodent models of carcinogenesis. We tested the
      hypotheses that silibinin or silipide, silibinin formulated with phospholipids,
      delays tumour development in TRAMP or Apc(Min) mice, genetic models of prostate
      or intestinal malignancies, respectively. Mice received silibinin or silipide
      with their diet (0.2% silibinin equivalents) from weaning. Intervention with
      silipide reduced the size of well differentiated TRAMP adenocarcinomas by 31%.
      Silipide and silibinin decreased the incidence of poorly differentiated
      carcinomas by 61% compared to mice on control diet. Silipide decreased plasma
      levels of insulin-like growth factor (IGF)-1 by 36%. Levels of circulating IGF
      binding protein (IGFBP)-3 in mice on silipide or silibinin were 3.9- or 5.9-fold,
      respectively, elevated over those in control TRAMP mice. In Apc(Min) mice
      silibinin, but not silipide, had only a marginal adenoma number-reducing effect.
      The results cautiously support the advancement of silipide to the stage of
      clinical investigation in prostate cancer.

PMID- 18343655
TI  - Bioremediation of leachate from a green waste composting facility using waste
      derived filter media.
AB  - The evaluation of two waste-derived materials used to treat compost leachate by
      biofiltration is described in this paper. Nine biofilters were constructed using
      240 l, high density polyethylene containers. Three containers were filled without
      compaction with 200l of each of three types of filter media. Waste-derived filter
      media (compost and oversize) were compared to a mineral control (granite chips).
      The filters were fed with compost leachate from a typical green waste composting
      facility at hydraulic loading rates ranging from 0.05 m3/m3/day to 0.5 m3/m3/day
      over a period of twelve months. The oversize medium emerged as the most effective
      demonstrating characteristics of consistency of effluent quality and resilience
      to stress. The oversize medium produced an effluent of <10mg/l ammoniacal
      nitrogen on >95% of sampling occasions. The organic component of compost leachate
      was dominated by compounds that proved to be recalcitrant to biodegradation. The
      solids content of the treated effluent remained too high to be acceptable for
      direct discharge to a watercourse without further treatment and if discharge to a
      watercourse is to be considered, a polishing stage (e.g., reed bed) able to
      remove solids and dampen occasional peaks of ammoniacal nitrogen should be
      employed.

PMID- 18343656
TI  - Kinetic study of corn straw pyrolysis: comparison of two different three
      pseudocomponent models.
AB  - With heating rates of 20, 50 and 100 K min(-1), the thermal decomposition of corn
      straw samples (corn stalks skins, corn stalks cores, corn bracts and corn leaves)
      were studied using thermogravimetric analysis. The maximum pyrolysis rates
      increased with the heating rate increasing and the temperature at the peak
      pyrolysis rate also increased. Assuming the addition of three independent
      parallel reactions, corresponding to three pseudocomponents linked to the
      hemicellulose, cellulose and lignin, two different three-pseudocomponent models
      were used to simulate the corn straw pyrolysis. Model parameters of pyrolysis
      were given. It was found that the three-pseudocomponent model with n-order
      kinetics was more accurate than the model with first-order kinetics at most
      cases. It showed that the model with n-order kinetics was more accurate to
      describe the pyrolysis of the hemicellulose.

PMID- 18343657
TI  - Anaerobic degradation of benzoate: batch studies.
AB  - Response of benzoate along with phenol to different anaerobic inocula has been
      investigated in batch reactors. In Phase I, the anaerobic biodegradability of
      benzoate and phenol were evaluated using (a) washed acclimatized granular sludge
      (WAGS) collected from a passive phenol fed bench-scale up-flow anaerobic sludge
      blanket reactor (UASBR) and (b) unacclimatized flocculent sludge (UFS) from a
      UASB based sewage treatment plant (STP). The effect of varying concentrations of
      benzoate has been investigated in Phase II using acclimatized granular sludge
      (AGS) from a bench-scale UASBR. Extent of degradation of benzoate was more than
      the phenol. Increasing benzoate COD from 2500 to 11,700mg/L, resulted in decrease
      in (i) rate constant, k from 0.79 to 0.11/d and (ii) ultimate biochemical methane
      potential (microb, g CH4-COD formed/g benzoate COD) from 84% to 60%. Temporal
      trend conforming to logistic S-curve indicated stressed conditions at higher
      benzoate concentration. Benzoate degradation was found to be sensitive to nature
      as well as quantity i.e. food to microorganism (F/M) of inocula used.

PMID- 18343658
TI  - A rapid autolytic method for the preparation of protein hydrolysate from poultry
      viscera.
AB  - Protein hydrolysate was prepared from poultry viscera by a procedure involving
      autolysis for 6h at pH 2.8 and 55 degrees C followed by heat inactivation,
      filtration and drying. Recovery of nitrogen in the product was 87%. The process
      reduced the viable count of bacteria by 5-6logcfu/g. The product contained 84%
      protein, 6.5% ash and 8.8% moisture. Peptide analysis by gel filtration
      chromatography showed size in the range of 0.5-5kDa. RPHPLC exhibited the
      presence of hydrophilic peptides in higher concentration than that in trypsin
      digest of casein. Protein hydrolysate exhibited presence of all essential amino
      acids in comparison with reference protein except for methionine and threonine.
      The product possesses excellent solubility (>93%) over a pH range of 1-12.
      Efficacy of the product as a bacteriological media or feed supplement is
      discussed.

PMID- 18343659
TI  - New data on temperature optimum and temperature changes in energy crop digesters.
AB  - As a result of self-heating in anaerobic digesters when using energy crops in the
      feedstock, the influence of temperature on the digestion process came back into
      focus. The aim of this study was to investigate the impact of such temperature
      increases on process stability. Furthermore, different strategies for the
      transition from mesophilic to thermophilic conditions and the resulting methane
      yields at different temperature levels were evaluated. Two main effects were
      identified with different bio-slurries from agricultural biogas plants: (1) a
      failure of methane production connected to changes in the microbial community;
      and (2), a slow but continuous accumulation of propionic acid, though without an
      immediate effect on methane production. All strategies for increasing the
      operating temperature showed negative effects on digester performance, some with
      serious economic consequences for the operator. It was shown that methane yields
      at different temperature levels in the mesophilic and sub-thermophilic ranges are
      similar.

PMID- 18343660
TI  - Application of anaerobic ammonium-oxidizing consortium to achieve completely
      autotrophic ammonium and sulfate removal.
AB  - The simultaneous ammonium and sulfate removal was detected in an anammox reactor,
      consisted of ammonium oxidization with sulfate deoxidization, and subsequently
      traditional anammox process, in via of middle medium nitrite with solid sulfur
      and N2 as the terminal products. The pure anammox bacteria offered a great
      biotechnological potential for the completely autotrophic reaction indicated by
      batch tests. Denaturing gradient gel electrophoresis (DGGE) analysis further
      revealed that a new organism belonging to Planctomycetales was strongly enriched
      in the defined niche: the redox of ammonium and sulfate. The new species
      "Anammoxoglobussulfate" was so considered as holding a critical role in the
      ammonium oxidization with sulfate deoxidization to nitrite. Afterwards, the
      Planctomyces existing in the bacteria community performed the anammox process
      together to achieve the complete nitrogen and sulfate removal. The potential use
      of sulfate as electron acceptor for ammonium oxidizing widens the usage of
      anammox bacteria.

PMID- 18343661
TI  - Synthesis of novel N-diazeniumdiolates based on hyperbranched polyethers.
AB  - Novel N-diazeniumdiolate based on hyperbranched polyethers(HP-g-DACA/N(2)O(2))
      were prepared through a two-step synthesized route. The alkyltrimethoxysilane
      containing secondary amine groups (DACA) was used to modify the hydroxyl end
      groups of hyperbranched polyethers (HP) to obtain the precursor hyperbranched
      diamine (HP-g-DACA). Then HP-g-DACA was reacted with NO at 80psi pressure to be
      converted into N-diazeniumdiolates. The structures were confirmed using (13)C NMR
      and IR spectra. UV-vis spectroscopy measurement indicated that the aqueous
      solution of obtained HP-g-DACA/N(2)O(2) had a characteristic absorption at 246nm.
      The final HP-g-DACA/N(2)O(2) product showed NO releasing within the prolonged
      periods of time, and the apparent half-life t(1/2) was more than 11min in
      phosphate buffer at 37 degrees C. The total amount of NO released from HP-g
      DACA/N(2)O(2) could achieve to 0.43micromol/mg and was proportional to the
      modified degree of HP by DACA. In addition, the NO loading efficiency can be
      modulated by the modification degree of hyperbranched macromolecular end groups.

PMID- 18343662
TI  - Meclonazepam analogues as potential new antihelmintic agents.
AB  - New analogues of the potent antihelmintic meclonazepam were prepared and
      evaluated against Schistosoma mansoni. The biological data suggests substitution
      at positions 2 and 4 of meclonazepam could provide promising analogues for
      prophylactic and therapeutic activity against S. mansoni.

PMID- 18343663
TI  - Synthesis and antibacterial activity of littorachalcone and related diphenyl
      ethers.
AB  - Littorachalcone (1) and diacid 10 were synthesized by direct routes. The
      antibacterial activity of 1, 10 and synthetic precursors were evaluated.
      Dialdehyde 3a showed potent antibacterial activity.

PMID- 18343664
TI  - Treadmill walking with body weight support effect of treadmill, harness and body
      weight support systems.
AB  - This study aims to provide new knowledge on the principles of treadmill walking
      with body weight support (BWS) by qualifying and quantifying the effects on gait
      in 28 healthy individuals. Gait assessment included measuring trunk movements
      during different conditions. Walking overground and on a treadmill with and
      without harness, and on a treadmill with 30% dynamic and static body weight
      support, was assessed. Gait variables for all conditions were compared at 1.2m/s.
      On the treadmill, cadence increased, the trunk tilted more forwards, vertical
      acceleration increased and anteroposterior acceleration became more variable.
      Wearing a harness resulted in more restricted vertical acceleration. Walking with
      body weight support restricted acceleration in all directions. It also produced
      variable interstride trunk acceleration in the anteroposterior and vertical
      directions, but more consistent interstride trunk acceleration in the
      mediolateral direction. Static BWS gave larger differences than dynamic BWS.

PMID- 18343665
TI  - Asymmetric load-carrying in young and elderly women: relationship with lower limb
      coordination.
AB  - This study investigates balance during asymmetric load-carrying and how
      asymmetric loading affects lower limb coordination during gait. Walking with and
      without a hand-held bag was analyzed in five young and six elderly women using a
      6-camera VICON system and two force plates. Balance and lower limb coordination
      were compared when walking with and without a bag and also between age groups.
      While carrying a bag, the trunk, head, and upper arm were recruited in both young
      and elderly women. With the load, the contralateral hip abduction torque
      increased, whereas the ipsilateral hip torque decreased. Intralimb and interlimb
      coordinations did not vary with the different load conditions. The only
      difference observed between the groups was the contralateral shoulder abduction.
      The elderly group abducted their shoulders to a greater extent, even when walking
      without a bag.

PMID- 18343666
TI  - Vestibular rehabilitation by auditory feedback in otolith disorders.
AB  - Rehabilitation strategies have been applied successfully over the last few
      decades to initiate central compensation of the tonus imbalance and to facilitate
      substitution in different types of peripheral vestibular dysfunction. However,
      these vestibular rehabilitation strategies are often not successful in patients
      with isolated otolith disorders. The aim of the present study was therefore to
      evaluate a specific rehabilitation strategy for patients with an isolated otolith
      disorder by using an auditory feedback system. Thirteen patients, which suffered
      from different types of otolith disorders, but no other vestibular pathology and
      13 normal controls were included in this study. Vestibular rehabilitation
      exercises were performed daily over a 2-week period (weekends excluded). During
      all exercises the patients of the test group (n=13) obtained an acoustic feedback
      signal when their trunk angle velocity exceeded a preset level while the patients
      of the control group (n=13) performed the same exercises without auditory
      feedback. The most effective exercise in the test group was "walking eight tandem
      steps on a foam support surface". Approximately 85% of the patients showed a
      significant decrease of trunk sway in this condition. In contrast to these
      results, patients of the control group showed no significant improvement of
      postural control after the training. The results indicate that an auditory
      feedback rehabilitation program with exercises related to the specific
      neurotological disease could significantly improve the postural control in
      patients with otolith disorders.

PMID- 18343667
TI  - Julius Althaus (1833--1900). Neurologist and cultural polymath; founder of Maida
      Vale Hospital.
AB  - Born, educated and trained in Germany, Julius Althaus migrated to London at the
      start of a long career in neurological medicine. He was a voluminous writer on a
      wide range of topics in both general medicine and neurology, especially
      electrotherapy. In addition, his textbooks form a snapshot of current concepts of
      great historical interest in areas such as epilepsy and cerebrovascular disease.
      He was an early and very successful author in the field of popular science
      journalism. His writing also covered many topics of general interest and his
      readership was both professional and public alike. His multilingual skills and
      Continental derivation provided him with international connections, placing him
      at the advancing edge of neurological development. Both Althaus and his wife Anna
      were superb musicians, the centre of a wide circle of friends and like-minded
      acquaintances, and contributed substantially to the cultural life of London.
      Althaus played a major, almost single-handed role in the founding and development
      of the Maida Vale Hospital for Nervous Diseases. He left behind a great legacy of
      both culture and neurology for his adopted country.

PMID- 18343668
TI  - LSD1: oxidative chemistry for multifaceted functions in chromatin regulation.
AB  - Three years after its discovery, lysine-specific demethylase 1 remains at the
      forefront of chromatin research. Its demethylase activity on Lys4 of histone H3
      supports its role in gene repression. By contrast, the biochemical mechanisms
      underlying lysine-specific demethylase 1 involvement in transcriptional
      activation are not firmly established. Structural studies highlight a specific
      binding site for the histone H3 N-terminal tail and a catalytic machinery that is
      closely related to that of other flavin-dependent amine oxidases. These insights
      are crucial for the development of demethylation inhibitors. Furthermore, the
      exploration of putative non-histone substrates and potential signaling roles of
      hydrogen peroxide produced by the demethylation reaction could lead to new
      paradigms in chromatin biology.

PMID- 18343669
TI  - A new take on prions: preventing Alzheimer's disease.
AB  - Alzheimer's disease is a major neurodegenerative disease of the brain, the
      incidence of which increases dramatically in old age. Currently, no drugs are
      available to halt or slow the progression of this disease, which poses an ever
      expanding burden on health services, families and society. The prion protein has
      become infamous owing to its role as the causative agent of the transmissible
      spongiform encephalopathies such as Creutzfeldt-Jakob disease in humans. However,
      our view of the prion protein as an unwanted, harmful entity has been challenged
      recently. New data indicate that the normal cellular form of the prion protein
      might have a crucial role in suppressing the production of the amyloid-beta
      peptide, the neurotoxic molecule involved in the pathogenesis of Alzheimer's
      disease.

PMID- 18343670
TI  - Anticipating antiport in P-type ATPases.
AB  - Cation-transporting P-type ATPases show a high degree of structural and
      functional homology. Nevertheless, for many members of this large family, the
      molecular mechanism of transport is unclear; namely, whether transport is
      electrogenic or not and if countertransport is involved remains to be
      established. In a few well-studied cases such as the Na(+)-K(+)-ATPase, plasma
      membrane Ca(2+) ATPase (PMCA) and sarcoplasmic reticulum Ca(2+) ATPase (SERCA)
      countertransport has been clearly demonstrated. New data based on the crystal
      structure of SERCA now strongly indicate that countertransport could be mandatory
      for all P-type ATPases. This concept should be verified for other known and for
      all newly characterized P-type ATPases.

PMID- 18343671
TI  - Synthesis, SAR and in vitro evaluation of new cyclic Arg-Gly-Asp
      pseudopentapeptides containing a s-cis peptide bond as integrin alphavbeta3 and
      alphavbeta5 ligands.
AB  - The solid-phase synthesis of two diastereomeric cyclic pseudopeptides containing
      the Arg-Gly-Asp sequence and the dipeptide isostere 2-amino-3-oxotetrahydro-1H
      pyrrolizine-7a(5H)-carboxylic acid (GPTM) is described. Competition binding
      assays to purified alphavbeta3 and alphavbeta5 integrins with respect to
      [125I]echistatin showed a high inhibitory activity for the (2S,7aS)-GPTM
      derivative. Effects of the structural constraint induced by the two enantiomeric
      scaffolds (2R,7aR)-GPTM and (2S,7aS)-GPTM on the conformation of Arg-Gly-Asp
      sequence have been computationally investigated using as a reference the recently
      solved X-ray structure of cyclo(Arg-Gly-Asp-d-Phe-[N-Me]Val) in complex with the
      extracellular fragment of the alphavbeta3 receptor. The computational method
      disclosed the key role played by a bridging water molecule on differentiating the
      two ligands by a diverse stabilization of the ligand-protein complex.

PMID- 18343672
TI  - Evaluation of alpha,beta-unsaturated ketone-based probes for papain-family
      cysteine proteases.
AB  - The field of activity-based proteomics makes use of small molecule active site
      probes to monitor distinct subsets of enzymatic proteins. While a number of
      reactive functional groups have been applied to activity-based probes (ABPs) that
      target diverse families of proteases, there remains a continual need for further
      evaluation of new probe scaffolds and reactive functional groups for use in ABPs.
      In this study we evaluate the utility of the, alpha,beta-unsaturated ketone
      reactive group for use in ABPs targeting the papain-family of cysteine proteases.
      We find that this reactive group shows highly selective labeling of cysteine
      cathepsins in both intact cells and total cell extracts. We observed a variable
      degree of background labeling that depended on the type of tag and linker used in
      the probe synthesis. The relative ease of synthesis of this class of compounds
      provides the potential for further derivatization to generate new families of
      cysteine protease ABPs with unique specificity and labeling properties.

PMID- 18343673
TI  - Design, synthesis and pharmacological evaluation of hybrid molecules out of
      quinazolinimines and lipoic acid lead to highly potent and selective
      butyrylcholinesterase inhibitors with antioxidant properties.
AB  - A set of hybrid molecules were synthesized out of lipoic acid, alpha,omega
      diamines of different lengths serving as spacers, and cholinesterase (ChE)
      inhibiting [2,1-b]quinazolinimines. Depending on the length of the alkylene
      spacer the amide hybrids are inhibitors of acetylcholinesterase (AChE) with
      inhibitory activities of 0.5-4.6microM and inhibitors of butyrylcholinesterase
      (BChE) with activities down to 5.7nM, therefore greatly exceeding the inhibitory
      activities of the parent quinazolinimines by factors of up to 1000. Due to
      increasing activity at BChE with increasing length of the alkylene spacer
      approximately 100-fold selectivity toward BChE is reached with a hepta- and an
      octamethylene spacer. Kinetic measurements reveal competitive and reversible
      inhibition of both ChEs by the hybrids. Furthermore, cell viability and
      antioxidant activity (using the ORAC-fluorescein assay) of several hybrids were
      evaluated, showing cytotoxicity at concentrations from 3.7 to 10.2microM and
      antioxidant properties are in the range of 0.4-0.8 Trolox equivalents (lipoic
      acid=0.6).

PMID- 18343674
TI  - On the structured imperfections of bulk GaSb using high resolution transmission
      electron microscopy.
AB  - GaSb is a promising III-V direct band gap semiconductor with sphalerite type FCC
      structure. Its band gap value has made it an excellent candidate for the
      conversion of infrared radiation to electricity. The wafers of GaSb, that were
      studied, originated from ingots grown with the Liquid Encapsulated Chochralski
      method. In all cases, Energy Dispersive X-ray Spectroscopy and Particle Induced X
      ray Emission measurements demonstrated an excess of Sb. In the present work
      conventional transmission electron microscopy (CTEM) and high resolution electron
      microscopy (HRTEM) were used in order to determine the effect of the Sb excess in
      the structural characteristics of the material, mainly after thermal treatment. A
      structure model based on the ordering of the Sb antisites (Sb(Ga)) rather than
      the Ga vacancies (V(Ga)) is proposed for the observed modulation in small areas
      of the material.

PMID- 18343675
TI  - Serum and aqueous humour cytokine response and histopathological alterations
      during ocular Toxoplasma gondii infection in C57BL/6 mice.
AB  - Toxoplasma gondii, an obligate intracellular protozoan parasite, infects most
      species of warm-blooded animals, and in humans it causes toxoplasmosis. Healthy
      people that become infected rarely present clinical symptoms because the immune
      system prevents the parasite from causing illness. Congenital toxoplasmosis may
      result in abortion, hydrocephalus, as well as neurological and ocular disease
      (most frequently retinochoroiditis) of the newborn. In immunocompromised
      patients, reactivation of latent disease can cause encephalitis. Cell-mediated
      immunity to T. gondii antigens involves innate acute inflammatory responses and
      antigen-specific adaptive immunity. Considering the complexity of the
      immunological events triggered during toxoplasmosis, systemic and local responses
      were evaluated by cytokine measurements. Aqueous humour and serum were obtained
      from non-infected and T. gondii Me-49 strain infected C57BL/6 mice for cytokine
      quantification. Histopathological analyses were made with eyes enucleated from
      mice after 30 days of infection. ELISA assays showed an increase of IFN-gamma
      levels both in serum and aqueous humour of infected mice in opposition to a
      decrease in IL-10 levels. On the other hand, TGF-beta was high, whereas IL-12 and
      TNF-alpha were present in small levels in both groups. We also detected higher
      levels of IL-4 and IL-6 in aqueous humour than in serum of infected mice when
      compared to the control group. MIP-2 presented no significant differences between
      the two groups. Fas and Fas-L were also present in similar levels in serum of non
      infected and infected mice, but both chemokines were increased in the aqueous
      humour of infected mice. Histopathological analysis of infected mice showed
      inflammatory infiltrates around blood vessels and alteration of the outer
      photoreceptor segments, on the external and inner nuclear layer. Parasites were
      observed in 82% of eyes, inside the blood vessels associated with inflammatory
      infiltrate. Edema, characterized by the increase of interstitial spaces between
      the FTR, forming lacunae was also noted. These alterations take the form of
      projections (retino-vitreal), characteristic of retinochoroiditis. In conclusion,
      T. gondii infection of C57BL/6 mice revealed that cytokine patterns alone do not
      assure susceptibility or resistance against infection, thus reinforcing the
      notion that it is necessary more than cytokine dosage to determine Th1 or Th2
      profile in this model.

PMID- 18343676
TI  - Sensory motor mismatch within the supplementary motor area in the dystonic
      monkey.
AB  - Dystonia, a movement disorder characterized by abnormal postures, is associated
      in primary forms of the disease with subtle proprioceptive troubles and aberrant
      somatotopic representation in the somatosensory cortex (SC). However, it is
      unclear whether these sensory features are a causal phenomenon or a consequence
      of dystonia. The supplementary motor area proper (SMAp), a premotor cortical
      region, receives strong inputs from both the SC and basal ganglia. We
      hypothesized that disruption in sensory-motor integration within the SMAp may
      play a part in the pathophysiology of dystonia. Using a model of secondary
      dystonia obtained by 3-nitropropionic acid intoxication in rhesus monkeys, we
      first provide evidence that the SMAp was overexcitable in dystonic animals.
      Second, we show that proprioceptive inputs processed by SMAp neurons were
      dramatically increased with wider sensory receptive fields and a mismatch between
      sensory inputs and motor outputs. These findings suggest that abnormal sensory
      inputs impinging upon SMAp neurons play a critical role in the pathophysiology of
      dystonia.

PMID- 18343678
TI  - Onlay frontal cranioplasty using wire reinforced methyl methacrylate.
AB  - INTRODUCTION: Methyl methacrylate is a biologically inert alloplastic material
      that is commonly used to rebuild the calvarial vault. Since methyl methacrylate
      does not permit tissue incorporation it is susceptible to displacement and/or
      fracture. In order to increase the tensile strength of methyl methacrylate onlay
      cranioplasties, we use wire reinforced masonry techniques. PATIENT: A 56-year-old
      female presents with forehead asymmetry due to displacement and fracture of a
      silicone alloplastic implant. This patient, treated with onlay wire reinforced
      methyl methacrylate, demonstrates the utility of this novel technique. RESULTS:
      Wire is passed through 2-mm outer cortex tunnels like spokes on a wheel, around
      the perimeter of the defect to form a rebar grid. Methyl methacrylate is poured
      onto the rebar grid and contoured after it solidifies. CONCLUSIONS: Wire
      reinforced methyl methacrylate is a simple technique to improve the tensile
      strength of calvarial alloplastic reconstructions.

PMID- 18343677
TI  - Src kinase inhibition decreases thrombin-induced injury and cell cycle re-entry
      in striatal neurons.
AB  - Since Src kinase inhibitors decrease brain injury produced by intracerebral
      hemorrhage (ICH) and thrombin is activated following ICH, this study determined
      whether Src kinase inhibitors decrease thrombin-induced brain injury. Thrombin
      injections into adult rat striatum produced focal infarction and motor deficits.
      The Src kinase inhibitor PP2 decreased thrombin-induced Src activation,
      infarction in striatum and motor deficits in vivo. Thrombin applied to cultured
      post-mitotic striatal neurons caused: injury to axons and dendrites; many TUNEL
      positive neuronal nuclei; and re-entry into the cell cycle as manifested by
      cyclin D1 expression, induction of several other cell cycle genes and cyclin
      dependent kinase 4 activation. PP2 dose-dependently attenuated thrombin-induced
      injury to the cultured neurons; and attenuated thrombin-induced neuronal cell
      cycle re-entry. These results are consistent with the hypotheses that Src kinase
      inhibitors decrease injury produced by ICH by decreasing thrombin activation of
      Src kinases and, at least in part, by decreasing Src induced cell cycle re-entry.

PMID- 18343679
TI  - Temporary neurological dysfunction after surgery of the thoracic aorta: a
      predictor of poor outcome and impaired quality of life.
AB  - BACKGROUND: Transient neurological dysfunction (TND) consists of postoperative
      confusion, delirium and agitation. It is underestimated after surgery on the
      thoracic aorta and its influence on long-term quality of life (QoL) has not yet
      been studied. This study aimed to assess the influence of TND on short- and long
      term outcome following surgery of the ascending aorta and proximal arch. METHODS:
      Nine hundred and seven patients undergoing surgery of the ascending aorta and the
      proximal aortic arch at our institution were included. Two hundred and ninety
      patients (31.9%) underwent surgery because of acute aortic dissection type A
      (AADA) and 617 patients because of aortic aneurysm. In 547 patients (60.3%) the
      distal anastomosis was performed using deep hypothermic circulatory arrest
      (DHCA). TND was defined as a Glasgow coma scale (GCS) value <13. All surviving
      patients had a clinical follow up and QoL was assessed with an SF-36
      questionnaire. RESULTS: Overall in-hospital mortality was 8.3%. TND occurred in
      89 patients (9.8%). As compared to patients without TND, those who suffered from
      TND were older (66.4 vs 59.9 years, p<0.01) underwent more frequently emergent
      procedures (53% vs 32%, p<0.05) and surgery under DHCA (84.3% vs 57.7%, p<0.05).
      However, duration of DHCA and extent of surgery did not influence the incidence
      of TND. In-hospital mortality in the group of patients with TND compared to the
      group without TND was similar (12.0% vs 11.4%; p=ns). Patients with TND suffered
      more frequently from coronary artery disease (28% vs 20.8%, p=ns) and were more
      frequently admitted in a compromised haemodynamic condition (23.6% vs 9.9%,
      p<0.05). Postoperative course revealed more pulmonary complications such as
      prolonged mechanical ventilation. Additional to their transient neurological
      dysfunction, significantly more patients had strokes with permanent neurological
      loss of function (14.6% vs 4.8%, p<0.05) compared to the patients without TND.
      ICU and hospital stay were significantly prolonged in TND patients (18+/-13 days
      vs 12+/-7 days, p<0.05). Over a mean follow-up interval of 27+/-14 months,
      patients with TND showed a significantly impaired QoL. CONCLUSION: The
      neurological outcome following surgery of the ascending aorta and proximal aortic
      arch is of paramount importance. The impact of TND on short- and long-term
      outcome is underestimated and negatively affects the short- and long-term
      outcome.

PMID- 18343680
TI  - Matrix metalloproteinases do not properly work as peripheral blood biomarkers
      without taking into account the preanalytical impact of blood sampling.

PMID- 18343681
TI  - Quantification of cytokines and inflammatory mediators in a three-dimensional
      model of inflammatory arthritis.
AB  - Human recombinant IL-1beta and TNFalpha have been previously used to induce a
      cytokine response in canine chondrocytes. In order to establish this functional
      relation in a homologous system in vitro, we have developed both 2D and 3D models
      of inflammatory arthritis using canine recombinant cytokines in canine articular
      chondrocytes. IL-1beta and TNFalpha were cloned and subsequently expressed in
      Escherichia coli. The purified recombinant canine cytokines were used to simulate
      inflammation in vitro and the expression of typical inflammation markers such as
      proinflammatory cytokines (IL-1beta, IL-6, IL-8, GM-CSF and TNFalpha), enzyme
      mediators (MMP-3 MMP-13, iNOS, COX-2) and their catabolites (NO, PGE(2)) was
      measured. High expression of proinflammatory cytokines, enzyme mediators and
      their catabolites was only observed in IL-1beta/TNFalpha stimulated cells. We
      conclude that the canine IL-1beta and TNFalpha generated in this study are
      biologically active and equally effective in the canine cell culture systems.
      Inducing an inflammatory pathway by canine exogenous cytokines in canine
      chondrocytes provides a useful tool for the study of canine inflammatory
      arthritis.

PMID- 18343682
TI  - Comparison of matrix effects in HPLC-MS/MS and UPLC-MS/MS analysis of nine basic
      pharmaceuticals in surface waters.
AB  - When developing an LC-MS/MS-method matrix effects are a major issue. The effect
      of co-eluting compounds arising from the matrix can result in signal enhancement
      or suppression. During method development much attention should be paid to
      diminishing matrix effects as much as possible. The present work evaluates matrix
      effects from aqueous environmental samples in the simultaneous analysis of a
      group of 9 specific pharmaceuticals with HPLC-ESI/MS/MS and UPLC-ESI/MS/MS:
      flubendazole, propiconazole, pipamperone, cinnarizine, ketoconazole, miconazole,
      rabeprazole, itraconazole and domperidone. When HPLC-MS/MS is used, matrix
      effects are substantial and can not be compensated for with analogue internal
      standards. For different surface water samples different matrix effects are
      found. For accurate quantification the standard addition approach is necessary.
      Due to the better resolution and more narrow peaks in UPLC, analytes will co
      elute less with interferences during ionisation, so matrix effects could be
      lower, or even eliminated. If matrix effects are eliminated with this technique,
      the standard addition method for quantification can be omitted and the overall
      method will be simplified. Results show that matrix effects are almost eliminated
      if internal standards (structural analogues) are used. Instead of the time
      consuming and labour-intensive standard addition method, with UPLC the internal
      standardization can be used for quantification and the overall method is
      substantially simplified.

PMID- 18343683
TI  - Optimum conditions for production and purification of human papillomavirus type
      16 L1 protein from Saccharomyces cerevisiae.
AB  - Several prophylactic human papillomavirus (HPV) vaccines have been developed
      based on virus-like particles (VLPs) made from viral L1 proteins. A substantial
      number of VLPs is necessary for biochemical characterization and diagnostic test
      development. To establish the optimum conditions for production and purification
      of HPV L1 in the yeast expression system we varied the amount and nature of the
      carbon source and evaluated HPV 16 L1 recovery by three purification methods.
      Maximally threefold more HPV 16 L1 was produced with a 4% carbon source than with
      a 2% carbon source. In addition, the productivity of HPV 16 L1 varied by 25%
      depending on the combination of glucose and galactose in the 4% carbon source. We
      introduced an ammonium sulfate precipitation step in place of the
      ultracentrifugation using a sucrose cushion routinely used for HPV L1
      purification, and optimized the purification by cation-exchange chromatography.
      Overall L1 protein recovery using the ammonium sulfate precipitation method was
      30%, the highest recovery achieved so far. The purified HPV 16 L1 protein
      successfully self-assembled into VLPs. Purification by ammonium sulfate
      precipitation was maximally 15 times greater than ultracentrifugation on a
      sucrose cushion. We anticipate that our procedures for production and
      purification will reduce the cost, time and labor involved in obtaining
      sufficient yields of VLPs.

PMID- 18343684
TI  - Spina cortica and Tapetum spinosus, two new microstructures of flight feathers:
      description, function and distribution in modern birds.
AB  - The importance of feathers for the avian group has made them one of the most
      studied epidermal structures both from the morphological and evolutionary point
      of view. Surprisingly, our observations by Scanning Electron Microscopy detected
      the presence of two structures widely distributed within different avian groups
      and not yet described. In this paper we describe these two new structures (Spina
      cortica and Tapetum spinosus) and map their distribution within modern birds. The
      S. cortica is a thorn-like microstructure that grows on the barb cortex and the
      T. spinosus is the assemblage of these thorns. The distribution of these new
      structures among birds and their morphological diversity could be of great
      interest to taxonomists and evolutionary biologists interested in the origin of
      bird flight.

PMID- 18343685
TI  - The immune and stress responses of Atlantic cod to long-term increases in water
      temperature.
AB  - Sea-caged cod are limited in their movements in the water column, and thus can be
      exposed to large seasonal ( approximately 0-20 degrees C) temperature
      fluctuations. To investigate the physiological response of Atlantic cod to summer
      like increases in temperature, we exposed 10 degrees C acclimated juvenile cod to
      a graded thermal challenge (1 degrees C increase every 5 days) and measured: (1)
      plasma cortisol and glucose levels; (2) the respiratory burst activity of blood
      leukocytes; and (3) the expression of specific immune-related genes [MHC Class I,
      Interleukin-1beta (IL-1beta), beta2-microglobulin (beta2-M), Immunoglobulin M
      (IgM)-light (L) and -heavy (H) chains] in the blood using quantitative reverse
      transcription-polymerase chain reaction (QRT-PCR). The experiment was stopped at
      19.1 degrees C, with 26.7% of the fish surviving to this point. Plasma glucose
      levels increased slightly at 16 and 18 degrees C (by 1.39- and 1.74-fold,
      respectively), in contrast, cortisol levels were elevated significantly (by 2.9
      fold) at 16 degrees C but returned to control levels thereafter. The effect of
      increasing temperature on the expression of immune related genes in blood cells
      (leukocytes) was variable and depended on the gene of interest. The expression of
      IgM-H remained stable for the duration of the experiment. In contrast, IL-1beta
      expression was increased significantly (by approximately 25-fold) at 19 degrees C
      as compared to time-matched control fish, and changes in the expression of beta2
      M, MHC Class I and IgM-L followed a pattern similar to that seen for cortisol:
      increasing at 16 degrees C (by 4.2-, 5.3- and 17-fold, respectively), but
      returning to pre-stress levels by 19 degrees C. Interestingly, increasing
      temperatures had no effect on respiratory burst activity. This study is the first
      to examine the effects of a chronic regimen of increasing temperature on the
      stress physiology and immunology of a marine teleost, and suggests that immune
      function is influenced by complex interactions between thermal effects and
      temperature-induced stress (elevated circulating cortisol levels).

PMID- 18343686
TI  - The neural mechanism underlying the female advantage in identifying negative
      emotions: an event-related potential study.
AB  - Previous studies have extensively reported an advantage of females in identifying
      negative facial emotions as compared with males. Nevertheless, why females are
      better in performance relative to males during emotion recognition tasks is still
      unknown, and the neural mechanism(s) underlying this phenomenon has yet to be
      directly investigated. As facial affects convey emotional information which is
      adaptively important and the recognition of a given facial affect generally
      evokes individuals' emotion of the same type [Dimberg, U., 1997. Facial
      reactions: rapidly evoked emotional responses. J. Psychophysiol. 11, 115-123],
      the present study assumes that the female advantage in emotion recognition may
      result from the attenuated sensitivity of males to emotionally negative stimuli
      of lesser valence intensity compared to that of females. In contrast, each gender
      may be comparably sensitive to emotionally negative stimuli of enhanced salience
      as suggested by the emotional negativity bias. To test this hypothesis, event
      related potentials were recorded for highly negative (HN), moderately negative
      (MN), and Neutral deviant images while subjects (15 males, 15 females) perform a
      standard/deviant categorization task, irrespective of the emotional valence of
      deviants. The results demonstrated more negative ERP deflections during HN
      condition than during MN and Neutral conditions at early N2 and later P3
      components, irrespective of gender. Moreover, MN condition elicited significantly
      more negative deflections than the Neutral condition across N2 and P3 components
      only in females, and the MN-Neutral difference waveform in females during 250-450
      ms interval was localized to the right prefrontal cortex. Thus, apart from the
      increased sensitivity of both genders to the highly negative stimuli, the present
      study demonstrated that women, instead of men, are sensitive to emotionally
      negative stimuli of lesser saliency, which may be an important mechanism
      underlying the female advantage in identifying negative emotions, and the right
      prefrontal cortex may be the neural basis underlying the female-specific
      sensitivity to emotionally negative stimuli of lesser salience.

PMID- 18343687
TI  - A bilateral cortico-bulbar network associated with breath holding in humans,
      determined by functional magnetic resonance imaging.
AB  - Few tasks are simpler to perform than a breath hold; however, the neural basis
      underlying this voluntary inhibitory behaviour, which must suppress spontaneous
      respiratory motor output, is unknown. Here, using blood oxygen level-dependent
      functional magnetic resonance imaging (BOLD fMRI), we investigated the neural
      network responsible for volitional breath holding in 8 healthy humans. BOLD
      images of the whole brain (156 brain volumes, voxel resolution 3x3x3 mm) were
      acquired every 5.2 s. All breath holds were performed for 15 s at resting
      expiratory lung volume when respiratory musculature was presumed to be relaxed,
      which ensured that the protocol highlighted the inhibitory components underlying
      the breath hold. An experimental paradigm was designed to dissociate the time
      course of the whole-brain BOLD signal from the time course of the local, neural
      related BOLD signal associated with the inhibitory task. We identified a
      bilateral network of cortical and subcortical structures including the insula,
      basal ganglia, frontal cortex, parietal cortex and thalamus, which are in common
      with response inhibition tasks, and in addition, activity within the pons. From
      these results we speculate that the pons has a role in integrating information
      from supra-brainstem structures, and in turn it exerts an inhibitory effect on
      medullary respiratory neurones to inhibit breathing during breath holding.

PMID- 18343688
TI  - Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease.
AB  - We performed univariate and multivariate discriminant analysis of FDG-PET scans
      to evaluate their ability to identify Alzheimer's disease (AD). FDG-PET scans
      came from two sources: 17 AD patients and 33 healthy elderly controls were
      scanned at the University of Michigan; 102 early AD patients and 20 healthy
      elderly controls were scanned at the Technical University of Munich, Germany. We
      selected a derivation sample of 20 AD patients and 20 healthy controls matched on
      age with the remainder divided into 5 replication samples. The sensitivity and
      specificity of diagnostic AD-markers and threshold criteria from the derivation
      sample were determined in the replication samples. Although both univariate and
      multivariate analyses produced markers with high classification accuracy in the
      derivation sample, the multivariate marker's diagnostic performance in the
      replication samples was superior. Further, supplementary analysis showed its
      performance to be unaffected by the loss of key regions. Multivariate measures of
      AD utilize the covariance structure of imaging data and provide complementary,
      clinically relevant information that may be superior to univariate measures.

PMID- 18343689
TI  - Evolution of syncarpy and other morphological characters in African Annonaceae: a
      posterior mapping approach.
AB  - The congenital fusion of carpels, or syncarpy, is considered a key innovation as
      it is found in more than 80% of angiosperms. Within the magnoliids however,
      syncarpy has rarely evolved. Two alternative evolutionary origins of syncarpy
      were suggested in order to explain the evolution of this feature: multiplication
      of a single carpel vs. fusion of a moderate number of carpels. The magnoliid
      family Annonaceae provides an ideal situation to test these hypotheses as two
      African genera, Isolona and Monodora, are syncarpous in an otherwise apocarpous
      family with multicarpellate and unicarpellate genera. In addition to syncarpy,
      the evolution of six other morphological characters was studied. Well-supported
      phylogenetic relationships of African Annonaceae and in particular those of
      Isolona and Monodora were reconstructed. Six plastid regions were sequenced and
      analyzed using maximum parsimony and Bayesian inference methods. The Bayesian
      posterior mapping approach to study character evolution was used as it accounts
      for both mapping and phylogenetic uncertainty, and also allows multiple state
      changes along the branches. Our phylogenetic analyses recovered a fully resolved
      clade comprising twelve genera endemic to Africa, including Isolona and Monodora,
      which was nested within the so-called long-branch clade. This is the largest and
      most species-rich clade of African genera identified to date within Annonaceae.
      The two syncarpous genera were inferred with maximum support to be sister to a
      clade characterized by genera with multicarpellate apocarpous gynoecia,
      supporting the hypothesis that syncarpy arose by fusion of a moderate number of
      carpels. This hypothesis was also favoured when studying the floral anatomy of
      both genera. Annonaceae provide the only case of a clear evolution of syncarpy
      within an otherwise apocarpous magnoliid family. The results presented here offer
      a better understanding of the evolution of syncarpy in Annonaceae and within
      angiosperms in general.

PMID- 18343690
TI  - Random local neighbor joining: a new method for reconstructing phylogenetic
      trees.
AB  - We have developed a new method for reconstructing phylogenetic trees called
      random local neighbor-joining (RLNJ). Our method is different from the neighbor
      joining method (NJ) of Saitou and Nei and affords a more thorough sampling of
      solution space by randomly searching for local pair of neighbors in each step.
      Results using the RLNJ method to analyze yeast data show an increasing
      possibility to get a smaller S value (sum of branch lengths) compared with the NJ
      method as cases with more taxa are analyzed and many individual runs using the
      RLNJ method usually generate more than one topology with small S values. Computer
      simulation shows the fact that the RLNJ method can improve the possibility of
      recovering correct topology significantly by affording more than one topology. In
      addition, when using the RLNJ method, computer simulation also shows that the
      proportion of correct topologies (P(C)) will increase as the number of different
      topologies decreases and as the proportion of "most frequent topology" increases.
      Thus, the number of different topologies and the proportion of "most frequent
      topology" can be used as auxiliary criteria to evaluate reliability of a
      phylogenetic tree.

PMID- 18343691
TI  - Arthroscopic capsular release for posttraumatic shoulder stiffness.
AB  - Severe pain and shoulder stiffness after soft tissue trauma or fracture is a
      major cause of dysfunction. Some patients may have residual, resistant,
      significant shoulder stiffness that causes long-term functional impairment. This
      study reports the results of arthroscopic capsular release in 21 patients who
      presented with posttraumatic stiff shoulders resistant to nonoperative therapy.
      They underwent arthroscopic circumferential capsular and subacromial release of
      adhesions under interscalene block, followed with immediate regular
      physiotherapy. A highly significant improvement in the range of motion (ROM) was
      achieved immediately postoperatively (P < .0001). At 6 months, a mean 48% of the
      ROM gain was lost. Thereafter, ROM steadily improved to a mean net gain of 110%
      compared with the immediate postoperative time (mean follow-up, 33 months). Most
      patients (95%) expressed satisfaction with their outcome. Arthroscopic capsular
      release is a useful treatment for resistant posttraumatic stiff shoulder,
      particularly to alleviate of pain and restore a functional ROM.

PMID- 18343692
TI  - Nonclassical secretion of human catalase on the surface of CHO cells is more
      efficient than classical secretion.
AB  - There is a great demand for improved production of therapeutic proteins using
      mammalian cell expression systems and transgenic animals. There have been
      intensive endeavors to optimize production at the transcriptional and
      translational levels, but comparatively little attention has been paid to the
      secretory level, especially to nonclassical secretion. To compare the
      efficiencies of classical and nonclassical secretion, we expressed GFP-tagged
      human catalase conjugated with a classical signal peptide and with several short
      peptides derived from mouse Engrailed 2 (mEN2) homeoprotein for nonclassical
      secretion and internalization in CHO cells. Surprisingly, the results showed that
      the secretory efficiency was significantly greater (up to 2.3 fold) than
      classical secretion when the fusion protein was driven by the secretory sequence
      (SS) of mEN2, and up to 1.9 fold when the classical secretion process was
      modified by incorporating the internalization sequence (IS) of mEN2. The effect
      of these short peptides on nonclassical secretion and internalization may
      indicate potential applications in the improved production of complex therapeutic
      proteins in mammalian cell expression systems and transgenic animals.

PMID- 18343693
TI  - Cellular mechanism of adrenalin stimulated chloride secretion via beta
      adrenoceptor in T84 cells.
AB  - In the present study, the intracellular regulatory pathways involved in the
      adrenalin-stimulated chloride secretion across T84 cells were investigated.
      Biphasic characteristics were observed in the Isc response to the basolateral
      addition of adrenalin (0.25 nM-100 microM). The biphasic response was almost
      abolished by removing ambient Cl(-). Chloride secretion was found to depend on
      the activities of basolaterally located Na+-K+-2Cl(-) cotransporters and K+
      channels. The alpha-adrenoceptor antagonist phentolamine did not have any effect
      on either phase of adrenalin-induced Isc, while after pretreatment of the beta
      adrenoceptor antagonist propranolol, the adrenalin-induced Isc was substantially
      abolished, suggesting the biphasic response may be mediated by the beta
      adrenoceptor. Under whole cell patch-clamp conditions, T84 cells responded to
      adrenalin with a rise in inward current. The current, which exhibited a linear I
      V relationship and time- and voltage-independent characteristics, was inhibited
      by the chloride channel blocker DPC and the reverse potential was close to the
      equilibrium potential for Cl(-) (0 mV), implying that the current was Cl(-)
      selective. When preloaded with a Ca2+-chelating agent, BAPTA/AM did not affect
      the Isc response to adrenalin, whereas the Isc was destroyed by pretreating the
      cells with an adenyl cyclase inhibitor, MDL12330A. These observations were
      further supported by the intracellular [cAMP] measurement experiment, indicating
      that adrenalin induced chloride secretion could be mediated by a beta
      adrenoceptor only involving cAMP as an intracellular second messenger.

PMID- 18343694
TI  - Inhibitory role of focal adhesion kinase on anoikis in the lung cancer cell A549.
AB  - Resistance to anoikis is a characteristic of malignant cells with increased
      tumorigenesis and metastasis. Altered FAK activity has been strongly implicated
      in the development, growth, progression, and metastasis of human cancers, but the
      mechanism of FAK in regulating anoikis is unknown. In this study, the resistance
      anoikis role of FAK and its downstream mediators was evaluated in the human lung
      cancer cell line A549. It has been shown that down regulation of FAK stimulates
      the apoptosis of cells and the down-regulation of p-ERK, p-PI3K, p-Src, and p
      p38. Furthermore, in detached A549 cells, increased FAK phosphorylations (Tyr397,
      Tyr861, Tyr925) were detected in a time-dependent manner, and the specific
      inhibitors of MEK1, PI3K, and Src (PD98059, LY294002, and PP2) partly abolished
      the resistance to the anoikis characteristic of cancer cells. Altogether, our
      data suggested that Src is involved in the progress of detachment-induced FAK
      activation in lung tumor cells. PI3K/AKT, MAPK-ERK, and perhaps MAPK-p38 but not
      MAPK-JNK, appear to be the key downstream effectors of FAK in mediating cell
      survival. The increased FAK activity upon cell detachment may contribute to the
      metastasis potential of malignant tumors.

PMID- 18343695
TI  - Motivationally neutral stimulation of the nucleus basalis induces specific
      behavioral memory.
AB  - The cholinergic system has been implicated in learning and memory. The nucleus
      basalis (NB) provides acetylcholine (ACh) to the cerebral cortex. Pairing a tone
      with NB stimulation (NBstm) to alter cortical state induces both associative
      specific tuning plasticity in the primary auditory cortex (A1) and associative
      specific auditory behavioral memory. NB-induced memory has major features of
      natural memory that is induced by pairing a tone with motivational reinforcers,
      e.g., food or shock, suggesting that the cholinergic system may be a "final
      common pathway" whose activation promotes memory storage. Alternatively, NB
      stimulation might itself be motivationally significant, either rewarding or
      punishing. To investigate these alternatives, adult male rats (n=7) first formed
      a specific NB-induced memory (CS=8.0kHz, 2.0s paired with NBstm, ISI=1.8s, 200
      trials), validated by post-training (24h) frequency generalization gradients (1
      15kHz) of respiration interruption that were specific to the CS frequency.
      Thereafter, they received the same level of NBstm that had induced memory, while
      confined to one quadrant of an arena, and later tested for place-preference,
      i.e., avoidance or seeking of the quadrant of NBstm. This NBstm group exhibited
      neither preference for nor against the stimulated quadrant, compared to sham
      operated subjects (n=7). The findings indicate that specific associative memory
      can be induced by direct activation of the NB without detectable motivational
      effects of NB stimulation. These results are concordant with a memory-promoting
      role for the nucleus basalis that places it "downstream" of motivational systems,
      which activate it to initiate the storage of the current state of its cholinergic
      targets.

PMID- 18343696
TI  - Recessive hereditary methemoglobinemia: two novel mutations in the NADH
      cytochrome b5 reductase gene.
AB  - We report the clinical and molecular characteristics of 6 new patients with
      recessive hereditary methemoglobinemia due to cytochrome b5 reductase deficiency.
      One patient was affected by Type-II disease with cyanosis and severe progressive
      neurological dysfunction, whereas the others displayed the benign Type-I
      phenotype. Methemoglobin levels ranged from 12.1% to 26.2% and cytochrome b5
      reductase activity from 0 to 10% of normal. Eight different mutations were
      detected among the twelve mutated alleles identified, one splicing mutation, two
      stop codon, and five missense. Two mutations c. 82 C>T(Gln27STOP) and c. 136
      C>T(Arg45Trp) are new. Prenatal diagnosis was performed in the family with Type
      II disease.

PMID- 18343697
TI  - Mitochondrial mediation of environmental osmolytes discrimination during
      osmoadaptation in the extremely halotolerant black yeast Hortaea werneckii.
AB  - We have investigated the mitochondrial responses to hyperosmotic environments of
      ionic (4.5 M NaCl) and non-ionic (3.0 M sorbitol) osmolytes in the most halo/osmo
      tolerant black yeast, Hortaea werneckii. Adaptation to both types of osmolytes
      resulted in differential expression of mitochondria-related genes. Live-cell
      imaging has revealed a condensation of mitochondria in hyperosmotic media that
      depends on osmolyte type. In the hypersaline medium, this was accompanied by
      increased ATP synthesis and oxidative damage protection, whereas adaptation to
      the non-ionic osmolyte resulted in a decrease in ATP synthesis and lipid
      peroxidation level in mitochondria. A proteomic study of the mitochondria
      revealed preferential accumulation of energy metabolism enzymes in the
      hypersaline medium, and accumulation of protein chaperones in the non-ionic
      osmolyte. The HwBmh1/14-3-3 protein, localized to mitochondria in hypersaline
      conditions, and not at optimal salinity, suggesting its role in differential
      perception of ionic and non-ionic osmolytes in H. werneckii.

PMID- 18343698
TI  - Riboflavin treatment in a case with l-2-hydroxyglutaric aciduria.
AB  - L-2-hydroxyglutaric aciduria (LHGuria) is a rare neurometabolic disorder, which
      has characteristic clinical and laboratory features. The recent findings imply
      that LHG dehydrogenase is responsible for the disease and is FAD-dependent.
      Therefore, it might be expected that riboflavin could enhance any residual
      activity. We present our observations from nearly 2-year-long riboflavin
      treatment in a 16-year-old boy with LHGuria. During riboflavin treatment of 100
      mg/d, partial improvement in his cognitive and motor performances was observed.
      Urinary LHG excretion decreased from 5990 mmol/mol creatinine to 1490 mmol/mol
      creatinine. Moreover, when riboflavin treatment was interrupted, significant
      disturbances in both symptoms and urinary LHG excretion (6360 mmol/mol
      creatinine) occurred in the patient. After the resettlement of riboflavine
      treatment, the patient resumed to his previous clinical status in a week. The
      improvement went further minimally under the dose of 200mg/d, but no further
      improvement happened with 300 mg/d. The present case suggests that riboflavin
      could be considered as a potential therapeutic approach in LHGuria until the
      optimal treatment of LHGuria is established.

PMID- 18343699
TI  - Self-contacts in Asx and Glx residues of high-resolution protein structures: role
      of local environment and tertiary interactions.
AB  - In protein structures, side-chains of asparagine and aspartic acid (Asx) and
      glutamine and glutamic acid (Glx) can approach their own backbone nitrogen or
      carbonyl group. We have systematically analyzed intra-residue contacts in Asx and
      Glx residues and their secondary structure preferences in two different datasets
      consisting of 500 and 1506 high-resolution structures. Intra-residue contact in
      an Asx/Glx residue between the heavy atoms of side-chain and main-chain
      functional groups of the same residue was investigated irrespective of whether
      such contacts are due to hydrogen bonding or not. Our search yielded 563 and 1462
      cases of self-contacting Asx and Glx residues from the two datasets. Two
      important observations have been made in this analysis. First, self-contacts
      involving side-chain oxygen and backbone nitrogen atoms in majority of Asx
      residues are not due to hydrogen bonds. In the second instance, surprisingly,
      side-chain and backbone carbonyl oxygens of a significant number of Asx and Glx
      residues approach each other. For a wide-range of accessible surface areas, self
      contacting residues are surrounded by less number of polar groups compared to all
      other Asx/Glx residues. In buried and partially buried regions, side-chain and
      main-chain functional groups of these residues together participate in
      simultaneous interactions with the available polar groups or water molecules.
      Asx/Glx residues with self-contacts are rarely observed in the middle of an alpha
      helix or a beta-strand. Asx/Glx side-chain having contact with its own backbone
      nitrogen shows different capping preferences compared to those having contact
      with its backbone oxygen. Examples of proteins with multiple self-contacting
      Asx/Glx residues are found. We speculate that mutation of a self-contacting
      residue in the buried or partially buried region of a protein will destabilize
      the structure. The results of this analysis will help in engineering protein
      structures and site-directed mutagenesis experiments.

PMID- 18343700
TI  - Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs.
AB  - OBJECTIVE: To study the toxicity of inhaled PGE1 (IPGE1) in healthy ventilated
      piglets. METHODS: Mechanically ventilated anesthetized piglets received either
      high dose IPGE1 (IPGE1 group) or nebulized saline (control group) continuously
      for 24h. Cardio-respiratory parameters, complete blood counts and serum
      electrolytes were monitored. Lung histology was evaluated by a masked pathologist
      for the severity (minimal, moderate, and severe) and extent (focal, multifocal,
      and diffuse) of histologic injury. RESULTS: Ten neonatal pigs were instrumented.
      Four received nebulized saline and six received high dose IPGE1. There was no
      evidence of adverse cardio-respiratory effects, bronchial irritation or
      hypernatremia related to IPGE1. Diffuse/multifocal alveolar edema and focal
      polymorphonuclear infiltration was observed in both the control and IPGE1 groups
      suggesting that alveolar alterations may be secondary to effects of mechanical
      ventilation. The most distinct histomorphological abnormalities observed in the
      IPGE1 animals were focal ulceration, flattening of the bronchial epithelium and
      loss of cilia of moderate to severe degree in the trachea and bronchi.
      CONCLUSION: In healthy piglets, inhalation of high dose IPGE1 was not associated
      with adverse cardiorespiratory effects, bronchial irritation, or hypernatremia
      and produced minimal signs of pulmonary toxicity even after 24h. Prolonged
      inhalation of high dose PGE1 therefore appears safe in newborn piglets.

PMID- 18343701
TI  - Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate
      disease in late-infantile neuronal ceroid lipofuscinosis.
AB  - Classical late-infantile neuronal ceroid lipofuscinosis (LINCL) is a hereditary
      neurodegenerative disease of childhood that is caused by mutations in the gene
      (CLN2) encoding the lysosomal protease tripeptidyl-peptidase I (TPPI). LINCL is
      fatal and there is no treatment of demonstrated efficacy in affected children but
      preclinical studies with AAV-mediated gene therapy have demonstrated promise in a
      mouse model. Here, we have generated mouse CLN2-mutants that express different
      amounts of TPPI activity to benchmark levels required for therapeutic benefits.
      Approximately 3% of normal TPPI activity in brain delayed disease onset and
      doubled lifespan to a median of approximately 9 months compared to mice
      expressing approximately 0.2% of normal levels. Expression of 6% of normal TPPI
      activity dramatically attenuated disease, with a median lifespan of approximately
      20 months which approaches that of unaffected mice. While the lifespan of this
      hypomorph is shortened, disease is late-onset, less severe and progresses slowly
      compared to mice expressing lower TPPI levels. For gene therapy and other
      approaches that restore enzyme activity, these results suggest that 6% of normal
      TPPI activity throughout the CNS of affected individuals will provide a
      significant therapeutic benefit but higher levels will be required to cure this
      disease.

PMID- 18343702
TI  - Single-day, three-dose treatment with fixed dose combination
      artesunate/sulfamethoxypyrazine/pyrimethamine to cure Plasmodium falciparum
      malaria.
AB  - OBJECTIVES: Malaria kills approximately 1.5 to 2.7 million people each year.
      Despite the introduction of artemisinin-based combination therapies (ACTs), the
      treatment of malaria is hampered by problems such as inadequate efficacy,
      recrudescence, early re-infection, low patient compliance, and high cost price of
      drugs. This study tested the hypothesis that the co-formulated fixed dose
      combination (FDC) artesunate/sulfamethoxypyrazine/pyrimethamine (As/SMP)
      administered as a 24-hour therapy with a dose interval of 12 hours is as
      efficacious and safe as the administration of the same drug over 3 days given
      with a dose interval of 24 hours, for the treatment of uncomplicated Plasmodium
      falciparum malaria in Ivory Coast. METHOD: Two hundred and twenty-one patients
      presenting with uncomplicated P. falciparum malaria were randomly assigned to
      either one of the two dosing schemes. Treatment efficacy was assessed using the
      current 28-day World Health Organization protocol, success being determined by
      absence of recrudescence and parasitemia on day 28. RESULTS: Both treatment
      regimens were highly efficacious, with a success rate of 100% (111/111) for the 3
      day therapy and 99% (109/110) for the 24-hour therapy. Only one patient in the 24
      hour therapy group showed late treatment failure. No serious adverse events or
      significant laboratory abnormalities were seen. CONCLUSION: The 24-hour therapy
      is as well tolerated and efficacious as the same medicament administered over 3
      days. This low cost and simplified three-pill treatment is certain to improve
      compliance.

PMID- 18343703
TI  - Self-monitoring of blood glucose in people with type 1 and type 2 diabetes living
      in France: the Entred study 2001.
AB  - OBJECTIVE: To describe the practice of self-monitoring blood glucose (SMBG)
      testing and to determine factors linked to SMBG in people with diabetes living in
      France. METHODS: The 2001 Entred study, a French national survey of people being
      treated for diabetes, is based on a representative sample of 10,000 adults who
      claimed reimbursement for oral hypoglycaemic agents and/or insulin in October to
      December 2001 and who were randomly extracted from the database of the major
      National Health Insurance System. A questionnaire was mailed to all these people
      and was returned by 36% of them, who were then classified into three groups: type
      1 diabetes (T1D, N=235); type 2 diabetes treated with insulin (iT2D, N=635); and
      type 2 diabetes treated with oral hypoglycaemic agents (oT2D, N=2689). Factors
      associated with SMBG were analyzed using logistic regression models with a step
      by-step forward approach. RESULTS: HbA(1c) was greater than or equal to 8% in 42%
      of people with T1D, 48% of those with iT2D and 21% of those with oTD2. Almost all
      of those treated with insulin performed SMBG. The frequency of self-monitoring
      was higher in T1D than in iT2D. In T1D, 58% of people reported they took at least
      three tests a day, as recommended in guidelines, which was more frequent in those
      who knew what HbA(1c) meant and in women. In iT2D, 74% reported that they took at
      least two tests a day, as recommended, and it was more frequent in those who knew
      what HbA(1c) meant, who reported at least one severe hypoglycaemic episode in
      2001 and who received dietary advice from their practitioner. In oT2D, 38%
      reported using SMBG (six tests a week on average), even though no official
      recommendation had been provided for these patients. SMBG was also more frequent
      in patients being treated with multiple oral hypoglycaemic agents, in those who
      benefited from a waiver of co-payment due to a chronic disease and in those, who
      had visited a diabetes specialist in 2001, reported they knew what HbA(1c) meant,
      received dietary advice and reported at least one severe hypoglycaemic episode in
      2001 and/or a history of diabetes complications. CONCLUSION: In France, as per
      the official recommendations, almost all people on insulin treatment use a SMBG
      device while, overall, their glucose control remains poor. More than one-third of
      those with oT2D regularly perform SMBG. In only 3% of people, the regular use of
      SMBG does not appear to be related to any special needs or events (such as
      insulin treatment, occurrence of severe hypoglycaemia or chronic complications).

PMID- 18343704
TI  - [Breast metastasis from vulvar carcinoma: case report and review of literature].
AB  - The breast metastases resulting of vulvar carcinoma are very rare, and represent
      exceptionally the first manifestation of the disease. We report the case of a 42
      year-old patient who underwent a treatment because of vulvar epidermoid
      carcinoma, right away metastatic at the level of the inguinal ganglia. The
      treatment consisted in a total vulvectomy with bilateral ganglial curretage,
      followed by external radiotherapy about the perineum and the inguinal ganglia.
      Three months after the end of her treatment, the patient presented with a nodula
      on the left outer breast with features of malignancy noticed by clinic and
      mammographic examination. The histologic study of the mammary biopsy showed
      epidermoid carcinoma of likely metastatic origin. A left Patey has been realized
      and confirmed the metastatic localization of epidermoid carcinoma with axillary
      ganglial metastasis (2N+/-7). Besides, this patient presented a right cervical
      ganglial parcel that the biopsy showed a metastatic localization of a vulvar
      carcinoma. A palliative chemotherapy type cyclophosphamid, adriblastin,
      cisplatine (CAP) has been admistrated during three cycles spaced out three weeks.
      The patient died 11 months after the supervene of the cerebral metastasis. We
      present this case because its rarety and to show the possibility of metastasis at
      the level of breast due to vulvar cancer. The clinicians must remember this
      possible tropism of the vulvar cancer for the breast, not only during the
      supervision and the complete examination as regards the disease spreading but
      also when the affection revealed unknown primary tumor. The diagnostic
      orientation is based on the mammography and the mammary biopsy. In this stage,
      the treatment is unfortunately palliative, the survival until a year is not more
      than 20%.

PMID- 18343705
TI  - Enhancement of ultraweak photon emission with 3 MHz ultrasonic irradiation on
      transplanted tumor tissues of mice.
AB  - We investigated photon emissions of various bio-samples which were induced by
      ultrasonic stimulation. It has been reported that ultrasonic stimulations induced
      the thermal excitation of the bio-tissues. After ultrasonic stimulation, any
      measurement of photon radiation in the visible spectral range has not been
      carried out yet. The instruments consisted of electronic devices for an
      ultrasonic generator of the frequency 3 MHz and a photomultiplier tube (PMT)
      system counting photons from bio-tissues. The transplanted tumor tissues of mice
      were prepared for the experiments and their liver and spleen tissues were also
      used for the controls. It was found that the continuous ultrasonic stimulations
      with the electrical power 2300 mW induced ultraweak photon emissions from the
      tumor tissues. The number of induced photon was dependent of the type of the
      tissues and the stimulation time intervals. The level of photon emission was
      increased from the mouse tumor exposed to the ultrasonic stimulations, and the
      changes were discriminated from those of the spleens and livers.

PMID- 18343706
TI  - Sonocatalytic degradation of acid red B and rhodamine B catalyzed by nano-sized
      ZnO powder under ultrasonic irradiation.
AB  - Nano-sized ZnO powder was introduced to act as the sonocatalyst after the
      treatment of high-temperature activation, and the ultrasound of low power was
      used as an irradiation source to induce nano-sized ZnO powder performing
      sonocatalytic degradation of acid red B and rhodamine B. At the same time, the
      effects of operational parameters such as solution pH value, initial
      concentration of dyestuff and addition amount of nano-sized ZnO powder have been
      examined in this paper. We found that the degradation ratios of acid red B and
      rhodamine B in the presence of nano-sized ZnO powder were much higher than that
      with only ultrasonic irradiation. However, the degradation ratio of acid red B
      was about two times higher than that of rhodamine B for the initial concentration
      of 10.0mg/L, addition amount of 1.0 g/L nano-sized ZnO powder, solution acidity
      of pH 7.0 and 60 min irradiation experimental condition. The difference of the
      degradation ratios can be illustrated by the difference of chemical forms of acid
      red B and rhodamine B in aqueous solution and the surface properties of nano
      sized ZnO particles. In addition, the researches on the kinetics of sonocatalytic
      reactions of acid red B and rhodamine B have also been performed and found to the
      follow pseudo first-order kinetics. All the experiments indicated that the
      sonocatalytic method in the presence of nano-sized ZnO powder was an advisable
      choice for the treatments of non- or low-transparent organic wastewaters in
      future.

PMID- 18343707
TI  - Predicting termination of atrial fibrillation based on the structure and
      quantification of the recurrence plot.
AB  - Predicting the spontaneous termination of the atrial fibrillation (AF) leads to
      not only better understanding of mechanisms of the arrhythmia but also the
      improved treatment of the sustained AF. A novel method is proposed to
      characterize the AF based on structure and the quantification of the recurrence
      plot (RP) to predict the termination of the AF. The RP of the electrocardiogram
      (ECG) signal is firstly obtained and eleven features are extracted to
      characterize its three basic patterns. Then the sequential forward search (SFS)
      algorithm and Davies-Bouldin criterion are utilized to select the feature subset
      which can predict the AF termination effectively. Finally, the multilayer
      perceptron (MLP) neural network is applied to predict the AF termination. An AF
      database which includes one training set and two testing sets (A and B) of Holter
      ECG recordings is studied. Experiment results show that 97% of testing set A and
      95% of testing set B are correctly classified. It demonstrates that this
      algorithm has the ability to predict the spontaneous termination of the AF
      effectively.

PMID- 18343708
TI  - Beta-catenin triggers nuclear factor kappaB-dependent up-regulation of hepatocyte
      inducible nitric oxide synthase.
AB  - Disruption of cell-to-cell contacts, as observed in many pathophysiological
      conditions, prime hepatocytes for compensatory hyperplastic response that
      involves induction of several genes, including proto-oncogenes and other gene
      targets of beta-catenin signaling pathway. By using cultured hepatocytes and
      experimental models of adherens junction disruption we have investigated changes
      in beta-catenin subcellular localization and their relationships with inducible
      nitric oxide synthase (iNOS) expression. Two experimental models were employed:
      (a) rat hepatocytes obtained by collagenase liver perfusion within the first 48 h
      of culture; (b) 48-h old cultured hepatocytes, transiently transfected or not
      with a plasmid encoding for dominant/negative inhibitory kappa B-alpha, exposed
      to ethylene glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid/LiCl
      treatment. beta-Catenin signaling and cellular localization, iNOS expression and
      nuclear factor kappaB involvement, were investigated using morphological, cell
      and molecular biology techniques. E-cadherin-mediated disruption of cell-to-cell
      contacts induces early beta-catenin translocation from membrane to cytoplasm and
      nuclear compartments, events that are followed by up-regulation of c-myc, cyclin
      D1 and beta-transducin repeat-containing protein expression. This, in turn,
      resulted eventually in iNOS induction that was mechanistically related to nuclear
      factor kappaB activation, as unequivocally shown in cells expressing dominant
      negative inhibitory kappa B-alpha. Our data indicate that E-cadherin disassembly
      and concomitant inactivation of glycogen synthase kinase-3beta result in nuclear
      factor kappaB-dependent induction of iNOS in hepatocytes.

PMID- 18343709
TI  - Brachypodium distachyon: making hay with a wild grass.
AB  - Brachypodium distachyon is a wild grass with a short life cycle. Although it is
      related to small grain cereals such as wheat, its genome is only a fraction of
      the size. A draft genome sequence is currently available, and molecular and
      genetic tools have been developed for transformation, mutagenesis and gene
      mapping. Accessions collected from across its ancestral range show a surprising
      degree of phenotypic variation in many traits, including those implicated in
      domestication of the cereals. Thus, given its rapid cycling time and ease of
      cultivation, Brachypodium will be a useful model for investigating problems in
      grass biology.

PMID- 18343710
TI  - Categorization in the wild.
AB  - In studying categorization, cognitive science has focused primarily on cultural
      categorization, ignoring individual and institutional categorization. Because
      recent technological developments have made individual and institutional
      classification systems much more available and powerful, our understanding of the
      cognitive and social mechanisms that produce these systems is increasingly
      important. Furthermore, key aspects of categorization that have received little
      previous attention emerge from considering diverse types of categorization
      together, such as the social factors that create stability in classification
      systems, and the interoperability that shared conceptual systems establish
      between agents. Finally, the profound impact of recent technological developments
      on classification systems indicates that basic categorization mechanisms are
      highly adaptive, producing new classification systems as the situations in which
      they operate change.

PMID- 18343711
TI  - Bilingualism in infancy: first steps in perception and comprehension.
AB  - Many children grow up in bilingual families and acquire two first languages.
      Emerging research is advancing the view that the capacity to acquire language can
      be applied equally to two languages as to one but that bilingual and monolingual
      acquisition nonetheless differ in some nontrivial ways. To probe the first steps
      toward acquisition, researchers recently have begun to use experimental methods
      to study preverbal bilingual infants. We review the literature in this growing
      field, focusing on how infants growing up bilingual use surface acoustic
      information to separate, categorize and begin to learn their two languages. These
      new data invite the expansion of standard linguistic theories to account for how
      a single architecture can support the acquisition of two languages
      simultaneously.

PMID- 18343712
TI  - Identifying and exploiting grain yield genes in rice.
AB  - Improved grain yield has been a major focus of crop breeding programs around the
      world. With the accomplishments of the Rice Genome Project, genes regulating
      several agronomically important traits related to grain yield, such as tiller
      number, grain number, grain size, and plant height, have recently been
      identified. Although these findings have not been enough to fully characterize
      the mechanisms that regulate each trait, these genes and knowledge of the
      molecular mechanisms involved provide a set of tools that can be combined to
      achieve tailor-made breeding suitable for various programs aimed at higher grain
      yield.

PMID- 18343713
TI  - Durable resistance to wheat stem rust needed.
AB  - The recent outbreak of a new wheat stem rust race capable of parasitizing many
      commercial wheat cultivars highlights the need for durable disease resistance in
      crop plants. More advanced breeding approaches using quantitative disease
      resistance genes and resistance gene pyramids are being used to combat wheat stem
      rust and other diseases, though widespread adoption of these breeding
      methodologies is needed to maintain resistance efficacy. Advances in
      understanding the molecular basis of plant disease resistance at both host and
      nonhost levels offers further possibilities for stem rust resistance using
      biotechnological approaches. However, truly durable resistance to wheat stem rust
      and other phytopathogens seems an unlikely prospect in the face of continually
      evolving pathogen populations.

PMID- 18343714
TI  - The role of cross-linking structures to the formation of one-dimensional nano
      organized polyaniline and their Raman fingerprint.
AB  - In the present work, the resonance Raman, UV-vis-NIR and scanning electron
      microscopic (SEM) data of nanorods (about approximately 300 nm in diameter) and
      nanofibers (about approximately 93 nm in diameter) of PANI are presented and
      compared. The PANI samples were synthesized in aqueous media with
      dodecybenzenesulfonic acid (DBSA) and beta-naphtalenesulfonic acid (beta-NSA) as
      dopants, respectively. The presence of bands at 578, 1400 and 1, 632 cm(-1) in
      the Raman spectra of PANI-NSA and PANI-DBSA shows that the formation of cross
      linking structures is a general feature of the PANI chains prepared in micellar
      media. It is proposed that these structures are responsible for the one
      dimensional PANI morphology formation. In addition, the Raman band at 609 cm(-1)
      of PANI fibers is correlated with the extended PANI chain conformation.

PMID- 18343715
TI  - Novel fluorescent pH sensor based on coumarin with piperazine and imidazole
      substituents.
AB  - A new coumarin derivative containing piperazine and imidazole moieties is
      reported as a fluorophore for hydrogen ions sensing. The fluorescence enhancement
      of the studied sensor with an increase in hydrogen ions concentration is based on
      the hindering of photoinduced electron transfer from the piperazinyl amine and
      the imidazolyl amine to the coumarin fluorophore by protonation. The presented
      sensor has a novel design of fluorophore-spacer-receptor(1)-receptor(2) format,
      which is proposed to sense two ranges of pH (from 2.5 to 5.5) and (from 10 to 12)
      instead of sensing one pH range. A model compound, in which the piperazinyl ring
      is absent, was synthesized as well to confirm the novel pH sensing of the
      proposed sensor.

PMID- 18343716
TI  - Theoretical study on the geometry and vibration of 1-[6-(4-Chlorophenyl)-1-[(6
      chloropyridin-3-yl)methyl]-2-[(6-chloropyridin-3-yl)methylsulfanyl]-4-methyl-1,6
      dihydropyrimidin-5-yl]ethanone.
AB  - The solid phase FT-IR and FT-Raman spectra of 1-[6-(4-chlorophenyl)-1-[(6
      chloropyridin-3-yl)methyl]-2-[(6-chloropyridin-3-yl)methylsulfanyl]-4-methyl-1,6
      dihydropyrimidin-5-yl]ethanone (C25H21Cl3N4OS) were recorded in the region 4000
      400 and 3500-100cm(-1), respectively. The vibrational spectra have been computed
      using density functional theory (B3LYP) and ab initio molecular orbital
      calculation (HF) with 6-31G(d, p) basis sets. A close agreement was achieved
      between the observed and calculated frequency by employing normal coordinate
      calculations. The observed and simulated spectra were found to be well
      comparable.

PMID- 18343717
TI  - Charge transfer interaction of 4-acetamidophenol (paracetamol) with 2,3-dichloro
      1,4-naphthoquinone: a study in aqueous ethanol medium by UV-vis spectroscopic and
      DFT methods.
AB  - 4-Acetamidophenol (paracetamol) is shown to form charge transfer complex with 2,3
      dichloro1,4-naphthoquinone in aqueous ethanol media exhibiting the unusual 2:1
      (paracetamol:quinone) stoichiometry. The complexation enthalpy and entropy have
      been estimated from the formation constant (K) determined spectrophotometrically
      at five different temperatures. In aqueous ethanol mixtures of varying
      composition K increases with increasing dielectric constant of the medium. This
      has been rationalized by calculating the electronic charge distribution in
      paracetamol molecule and its conjugate base at the DFT/B3LYP/6-31++G(d,p) level.
      The theoretically calculated vertical ionization potential of paracetamol also
      agrees with reported experimental value.

PMID- 18343718
TI  - A simple screening assay for receptor switching of avian influenza viruses.
AB  - BACKGROUND: Adaptation of the receptor-binding preference from alpha2,3- to
      alpha2,6-linked sialic acid is an essential step for an avian influenza virus to
      transmit efficiently in human population and become a pandemic virus. The
      currently available assays for receptor-binding preference are complex and not
      widely available. OBJECTIVES: A simple high-throughput screening assay will
      facilitate early detection of a potential pandemic virus, which is crucial for
      the prevention and control of the possible pandemic. We wanted to develop a
      simple assay to differentiate influenza viruses with alpha2,3- or alpha2,6-linked
      receptor-binding preference. STUDY DESIGN: The assay employs a specific sialidase
      (from Salmonella thyphimurium) that can eliminate alpha2,3-linked sialic acid
      from red blood cells. A reduction of hemagglutination titer indicates alpha2,3
      linked receptor preference in this assay. RESULTS: Using a panel of H5N1 avian
      influenza isolates and H1/H3 human influenza isolates, as well as mutated H5
      reverse genetics virus, the assay could accurately differentiate the viruses
      according to their receptor-binding preference. Furthermore, the assay was
      sufficiently sensitive to detect a minor variant with alpha2,6-linkage
      specificity in a background of alpha2,3-linkage-specific virus. CONCLUSIONS: We
      have developed a simple screening assay capable of detecting avian influenza
      viruses that have switched their receptor-binding preference.

PMID- 18343719
TI  - Evolution of tibial SSEP after traumatic spinal cord injury: baseline for
      clinical trials.
AB  - OBJECTIVE: To describe the spontaneous evolution of tibial somatosensory evoked
      potentials (tSSEPs) after spinal cord injury (SCI) and its relation to
      neurological and functional parameters. METHODS: tSSEPs were assessed in 297
      patients within five standardized time intervals throughout the first year after
      injury, along with neurological and functional parameters. RESULTS: Roughly 60%
      of the patients did not show any recordable tSSEP throughout the first year after
      injury. Approximately 20% had recordable potentials at every assessment stage and
      showed an improvement of tSSEP parameters over time. In about 10% of the
      patients, a potential recovered during the first year. In the remaining cases,
      potentials were inconsistently recordable. All groups showed a similar amount of
      neurological and functional improvement. CONCLUSIONS: Recordability, latencies
      and amplitudes of tSSEPs can change over time after SCI. The early recordability
      of a tSSEP is associated with a favorable functional and neurological status and
      outcome. In contrast, an initially absent tSSEP is not always associated with a
      poorer status and outcome but only in those 75% of the patients in whom the
      potential remains absent. SIGNIFICANCE: This exact description of the spontaneous
      improvements of neurophysiological, neurological and functional parameters after
      SCI is an important prerequisite in appraising the efficacy of new interventional
      therapies.

PMID- 18343720
TI  - Abnormal cortical excitability with preserved brainstem and spinal reflexes in
      sialidosis type I.
AB  - OBJECTIVE: To examine neurophysiological evidence of functional involvement of
      the brainstem and spinal cord and motor cortical excitability in sialidosis type
      I, a rare inherited neurodegenerative disorder caused by mutations in the NEU1
      gene. METHODS: We investigated particular pathways in the brainstem, spinal cord
      and motor cortex in 12 genetically proven cases of sialidosis type I by assessing
      blink reflex recovery cycle (BR), spinal reciprocal inhibition (RI), input-output
      curves (I/O), short interval intracortical inhibition (SICI), intracortical
      facilitation (ICF) and silent period (SP). RESULTS: The BR and RI were normal.
      The slope of I/O was significantly increased, and SICI and the duration of SP
      were reduced in sialidosis patients. CONCLUSIONS: Despite reports of pathology
      involving brainstem and anterior horn neurones, there were no obvious
      abnormalities in spinal and brainstem reflexes in the present patients,
      suggesting that the major clinical effects may be caused by changes at a level
      above the brainstem. SIGNIFICANCE: For the first time, the integrity of certain
      brainstem and spinal cord reflexes in addition to motor cortical facilitatory and
      inhibitory circuits has been assessed in genetically proven type I sialidosis.
      This provides new data to aid in understanding of the pathophysiology of motor
      system dysfunction in this condition.

PMID- 18343721
TI  - Celecoxib modulates hypertrophic signalling and prevents load-induced cardiac
      dysfunction.
AB  - In human hearts, the transition from cardiac hypertrophy to advanced heart
      failure (HF) is accompanied by a tremendous increase in Akt phosphorylation. In
      non-myocardial tissue, the cyclooxygenase (COX)-2 inhibitor celecoxib has been
      shown to COX-independently inhibit Akt signalling. We studied the effects of
      celecoxib on Akt signalling and hypertrophic response in myocardium. In rabbit
      isolated cardiac myocytes celecoxib concentration-dependently (10-100 micromol/L)
      inhibited the insulin-induced increase in phosphorylation of Akt and its
      downstream targets, GSK-3beta and p70 S6 kinase, by reducing the phosphorylation
      level of the upstream regulator PTEN. Inhibition of Akt signalling was
      accompanied by a significant suppression of characteristic features of cardiac
      hypertrophy: Celecoxib concentration-dependently suppressed the agonist-induced
      enhancement of total protein synthesis and BNP mRNA expression. In mice
      (C57BL/6NCrl) subjected to left ventricular (LV) pressure overload by aortic
      banding, celecoxib treatment (50mg x kg-1 x d-1) significantly attenuated LV
      dilation and contractile dysfunction compared with placebo-treated mice.
      Moreover, celecoxib significantly reduced mortality 8 weeks after banding. Thus,
      celecoxib can be used to titrate Akt signalling and hypertrophic response in
      myocardium. It reduces load-induced LV dilation, contractile dysfunction and
      mortality in vivo. This may have clinical implications for the prevention and
      treatment of maladaptive hypertrophy and its progression to HF in humans.

PMID- 18343722
TI  - Biomarkers of endothelial dysfunction are elevated and related to prognosis in
      chronic heart failure patients with diabetes but not in those without diabetes.
AB  - BACKGROUND: Biomarkers of endothelial dysfunction, such as soluble E-selectin,
      and von Willebrand factor (vWf) are elevated in patients with chronic heart
      failure (CHF). The impact of diabetes mellitus (DM) on these biomarkers, and
      their relation to prognosis remains unknown. AIMS: to investigate the impact of
      DM on plasma levels and the prognostic value of E-selectin and vWf in patients
      with CHF. METHODS AND RESULTS: Plasma levels of E-selectin and vWf were measured
      in 195 CHF patients with (n=48, 24.5%), and without DM, and in 116 age-matched
      healthy controls. Compared with controls, median plasma E-selectin levels were
      higher in CHF patients with DM (P=0.012), but not in CHF patients without DM
      (P=0.45); vWf levels were also higher in CHF patients with DM (P<0.001), but not
      without DM (P=0.108). E-selectin was associated with risk of recurrent ischaemic
      cardiovascular events among CHF patients with DM (HR 2.60; P=0.009), but not
      among patients without DM (HR 1.09; P=0.60) per 1 SD increment in log transformed
      variable. vWf was not related with outcome in CHF patients with or without DM.
      CONCLUSIONS: Plasma levels of E-selectin and vWf are elevated in CHF patients
      with DM but not in those without DM. High E-selectin levels may be associated
      with ischaemic events in patients with DM.

PMID- 18343723
TI  - Tissue inhibitor of metalloproteinases levels in patients with chronic heart
      failure: an independent predictor of mortality.
AB  - BACKGROUND: Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP)
      are involved in cardiac remodelling. The prognostic utility of TIMP is unknown in
      chronic heart failure (CHF). AIMS: We investigated the association of plasma
      levels of soluble MMP-9 and TIMP-1 with clinical, laboratory and
      echocardiographic parameters and estimated their prognostic value in the
      prediction of all-cause death. METHODS: MMP-9, TIMP-1, tumour necrosis factor
      alpha, and amino-terminal pro-brain natriuretic peptide were measured in 249
      consecutively enrolled CHF patients and 74 healthy individuals. RESULTS: After
      adjustment for age, sex and creatinine, levels of TIMP-1 (1640 vs. 735 ng/ml,
      P<0.001) but not MMP-9 were elevated in CHF patients compared to controls. During
      a median follow-up period of 2.5 years, 66 patients (27%) died. In multivariable
      Cox regression models TIMP-1 but not MMP-9 emerged as an independent predictor of
      all-cause death (hazard ratio per tertile, 3.5; 95% confidence interval [CI], 2.2
      5.1). In addition to the full set of univariately predictive clinical and
      serological markers, information on TIMP-1 significantly increased the area under
      the receiver operating characteristic curve from 0.77 (95% CI, 0.71-0.84) to 0.87
      (95% CI, 0.82-0.92). CONCLUSION: In stable CHF patients, TIMP-1 but not MMP-9 is
      of independent and incremental value regarding the prediction of all-cause death.

PMID- 18343725
TI  - Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer
      and outcome of radical treatment: a retrospective analysis of two randomised
      radiotherapy trials and one surgical cohort study.
AB  - BACKGROUND: Expression of intrinsic markers of tumour hypoxia and angiogenesis
      are important predictors of radiotherapeutic, and possibly surgical, outcome in
      several cancers. Extent of tumour hypoxia in localised prostate cancer is
      comparable to that in other cancers, but few data exist on the association of
      extent of tumour hypoxia with treatment outcome. We aimed to study the predictive
      value of intrinsic markers of tumour hypoxia and angiogenesis in localised
      prostate cancer, both in patients treated with radiotherapy and in those treated
      surgically. METHODS: We applied a new, needle biopsy tissue microarray (TMA)
      technique to study diagnostic samples from men with localised, previously
      untreated prostate cancer treated in two randomised controlled trials of
      radiotherapy-dose escalation. Multivariate analysis by Cox proportional hazards
      was done to assess the association between clinical outcome, in terms of
      biochemical control, and immunohistochemical staining of hypoxia inducible factor
      1 alpha (HIF-1 alpha), vascular endothelial growth factor (VEGF), and osteopontin
      expression. The analysis was repeated on an independent series of men with
      localised, previously untreated prostate cancer treated by radical prostatectomy.
      The main outcome was time to biochemical (ie, prostate-specific antigen [PSA])
      failure. FINDINGS: Between Oct 12, 1995, and Feb 5, 2002, 308 patients were
      identified from two prospective, randomised trials at the Royal Marsden Hospital,
      London and Sutton, UK, for the radiotherapy cohort and diagnostic biopsies were
      available for 201 of these patients. Between June 6, 1995, and Nov 4, 2005, 329
      patients were identified from the Aarhus University Hospital, Skejby, Denmark,
      for the prostatectomy cohort; of these, 40 patients were excluded because the
      tumour was too small to sample (19 patients), because the paraffin block was too
      thin (19 patients), or because the blocks were missing (two patients), leaving
      289 patients for analysis. For patients treated with radiotherapy, increased
      staining for VEGF (p=0.008) and HIF-1 alpha (p=0.02) expression, but not
      increased osteopontin expression (p=0.978), were significant predictors of a
      shorter time to biochemical failure on multivariate analysis, independent of
      clinical tumour stage, Gleason score, serum PSA concentration, and dose of
      radiotherapy. For patients treated with surgery, increased staining for VEGF
      (p<0.0001) and HIF-1 alpha (p<0.0001) expression, and increased osteopontin
      expression (p=0.0005) were each significantly associated with a shorter time to
      biochemical failure on multivariate analysis, independent of pathological tumour
      stage, Gleason score, serum PSA concentration, and margin status. INTERPRETATION:
      To our knowledge, this is the largest study of intrinsic markers of hypoxia and
      angiogenesis in relation to the outcome of radical treatment of localised
      prostate cancer. Increased expression of VEGF, HIF-1 alpha, and, for patients
      treated with surgery, osteopontin, identifies patients at high risk of
      biochemical failure who would be suitable for enrolment into trials of treatment
      intensification.

PMID- 18343726
TI  - Neutrophil priming, caused by cell membranes and microvesicles in packed red
      blood cell units, is abrogated by leukocyte depletion at collection.
AB  - BACKGROUND AND OBJECTS: Lipids with platelet activating factor (PAF)-like
      activity in supernatant of packed red blood cells (PRBC) cause priming of the
      neutrophil respiratory burst. This effect increases with length of storage.
      Washing of PRBC has been considered as a means to eliminate this effect; however,
      the role of the cellular component was not evaluated independently of the
      supernatant. The source of the inflammatory lipids of the supernatant is likely
      to be cell membranes altered during ageing in storage and therefore, washing will
      not eliminate neutrophil priming caused by transfusion of aged PRBC units. The
      ability of washed PRBC to prime mononuclear cells for another known effect of
      PAF, the production of IL-8, and the probability that this lipid activity is
      present on microparticles in PRBC supernatant were also investigated. MATERIALS
      AND METHODS: At collection 10 units of whole blood were split into two equal
      aliquots one filtered and one unfiltered. PRBC were prepared and stored at 4
      degrees C in CPD-AS5. Each week, fresh neutrophils were incubated with samples of
      washed PRBC and fixed. Change in CD11b, a marker known to increase on the surface
      of primed neutrophils, was determined by flow cytometry. To determine whether
      neutrophil priming ability of PRBC supernatant is contained on microvesicles,
      centrifuged and uncentrifuged supernatant samples were incubated with fresh
      neutrophils and change in CD11b expression was determined. Plasma IL-8 levels
      were also measured after exposure of monocytes from fresh whole blood to filtered
      and unfiltered washed PRBC with and without the addition of fMLP. RESULTS: Washed
      PRBC caused a 50-116% increase in CD11b neutrophil surface expression over
      baseline expression. Filtration of whole blood at collection reduced this CD11b
      up-regulation by 25-34%. Reduction of priming ability by filtration began on the
      day of collection and persisted for the storage life of the units. Centrifugation
      resulted in a reduction of CD11b up-regulation of 11-28% compared with unspun
      supernatant. Incubation of unfiltered PRBC resulted in priming of mononuclear
      leukocytes for IL-8 production with a 73-109% increase over baseline, but no
      increase over baseline was seen for incubation with filtered blood. CONCLUSION:
      Washing does not eliminate the ability of PRBC units to prime neutrophils and
      mononuclear cells, because the cellular component of PRBC, in addition to the
      supernatant, induces priming. Leukodepletion filters significantly reduce these
      effects compared with unfiltered PRBC. The in vitro beneficial effect of
      filtration lasts for the shelf life of 42 day units. The ability of PRBC
      supernatant to prime neutrophils is present on microvesicles.

PMID- 18343727
TI  - Treatment of chronic femoral osteomyelitis with platelet-rich plasma (PRP): a
      case report.
AB  - Chronic osteomyelitis is a serious problem in developing countries. A lot of
      patients with chronic osteomyelitis have to be treated for a very long period and
      get several operations including complete debridement, antibiotic bead implant,
      bone grafts, etc. However, traditional methods seem to be ineffective in some
      patients, who always have a high incidence of recurrence. We report a case of
      chronic osteomyelitis in bilateral femurs, which has been treated with long time
      antibiotic therapy, about twenty debridements, yet the sinus remained unhealed
      for over four years. At the end of this period, we used PRP to treat the unhealed
      sinus and obtained good results. Though the mechanism by which PRP treats chronic
      osteomyelitis is now unclear, the results encourage study further.

PMID- 18343728
TI  - The relation of post-traumatic stress symptoms to depression and pain in patients
      with accident-related chronic pain.
AB  - Symptoms of post-traumatic stress disorder (PTSD) are a common comorbidity in
      patients with a history of accident-related chronic pain and depression. However,
      little is known regarding the influence of PTSD in contributing to the affective
      distress, pain experience, and disability associated with chronic pain in this
      population. This study used structural equation modeling to examine 3 models that
      assess these relations in a sample of chronic pain patients with accident-related
      pain. Subjects were assessed for pain experience, depressive symptoms, anxiety,
      PTSD symptoms, pain disability, and relevant demographic variables. Pearson
      correlations indicated that symptoms of depression were significantly related to
      more severe pain, disability, and PTSD symptoms. PTSD symptoms were significantly
      associated with higher disability. The model of best fit indicated that after
      controlling for the influence of anxiety on the dependent measures, PTSD symptoms
      have a direct influence on severity of depressive symptoms, whereas depressive
      symptoms have a direct influence on pain intensity and an indirect impact on pain
      intensity by way of their effect on disability. These data point to the
      importance of unresolved PTSD symptoms in contributing to the level of
      depression, pain, and disability exhibited by chronic pain patients and highlight
      the need to consider directed and primary treatment of PTSD in pain
      rehabilitation programs. PERSPECTIVE: This study highlights the impact of
      symptoms of PTSD on levels of depression, disability, and pain in patients with
      pain secondary to physical injury. Our results suggest that pain rehabilitation
      programs provide directed interventions for PTSD symptoms among this population
      to improve pain treatment outcomes.

PMID- 18343729
TI  - Critical role of the rostral ventromedial medulla in early spinal events leading
      to chronic constriction injury neuropathy in rats.
AB  - Neuropathic pain is a major clinical problem, and several animal models have been
      developed to investigate its mechanisms and its treatment. In this report, the
      role of the rostral ventromedial medulla (RVM) in the early events of the chronic
      constriction injury (CCI) model was investigated in behavioral and
      electrophysiological experiments. Placing the 4 CCI ligatures around the sciatic
      nerve induced large discharges and residual ongoing activity in spinal
      nociceptive neurons. Two weeks after CCI ligation, the rats showed behavioral
      hyperalgesia and allodynia as well as increased ongoing activity and
      responsiveness of spinal nociceptive neurons to innocuous and noxious stimuli.
      Blockade of excitatory synapses in the RVM by a kynurenate microinjection (2 nmol
      in 0.5 muL) 5 minutes before placement of the sciatic ligatures had no immediate
      effect on spinal neuronal activity but largely prevented the activation of spinal
      neurons. In kynurenate microinjected rats, behavioral hyperalgesia and allodynia
      developed slowly and incompletely, which corresponded with an incompletely
      developed hyperexcitability of spinal neurons. To the best of our knowledge,
      these results show for the first time that the initial response to nerve damage
      requires facilitation from the RVM. PERSPECTIVE: The present and previous
      findings indicate that descending facilitation from brainstem nuclei critically
      contributes to the spinal hyperexcitability that underlies neuropathic pain. The
      present results indicate that this contribution begins at the very moment the
      nerve is damaged and should be prevented and treated accordingly.

PMID- 18343730
TI  - Osteoporosis and vertebral compression fractures-continued missed opportunities.
AB  - BACKGROUND CONTEXT: Untreated osteoporosis causes decreased bone mineral density,
      which predisposes to fragility fractures. Low-energy vertebral compression
      fractures are the most common type of osteoporotic fragility fracture. Prior
      studies have shown that only one-quarter of patients diagnosed with an
      osteoporotic fracture are referred or treated for osteoporosis. PURPOSE: To
      identify the rate of therapeutic interventions for patients aged 50 years and
      older within a capitated population who sustained low impact vertebral
      compression fractures over a 6-month period. STUDY DESIGN/SETTING: Retrospective
      observational study. PATIENT SAMPLE: The reports of all imaging studies of the
      chest, abdomen, and spine taken from July to December 2002 within a large
      military health-care system were queried on the Composite Health Computer System
      (CHCS). The sample included patients 50 years or older who had a low-energy
      vertebral compression fracture. OUTCOME MEASURES: The computerized medical
      records were examined for osteoporotic medication prescriptions, referrals to
      endocrinology, and to dual-energy X-ray absorptiometry (DEXA) scans. These
      results were compared with results obtained from a similar study on osteoporotic
      distal radius fractures. RESULTS: The records of 156 patients (average age:
      77.3y; 78 women, 78 men) meeting the inclusion criteria were analyzed to
      determine what proportion was followed-up with osteoporosis interventions. Within
      1 year after the fracture, 39% (37 females, 24 males) had undergone a DEXA scan,
      35% (37 females, 18 males) had been referred to endocrinology, 38% (47 females,
      12 males) were receiving active osteoporosis treatment, and 51% (55 females, 25
      males) were receiving any form of osteoporosis-directed medication. The rate of
      medical intervention was similar to the rate of intervention after distal radius
      fragility fractures (n=111; 30% active medication; 47% any osteoporosis
      medication) (p>.21). The rate of all interventions was significantly greater for
      women than men. CONCLUSIONS: Although the likelihood of intervention is slightly
      greater after vertebral compression fractures than for distal radius fractures,
      orthopedic surgeons, emergency room physicians, and primary care providers
      continue to miss opportunities, especially in males, to diagnose and/or initiate
      active therapeutic interventions for osteoporosis in patients presenting with
      osteoporosis-related fragility fractures.

PMID- 18343731
TI  - Translational cognition for decision support in critical care environments: a
      review.
AB  - The dynamic and distributed work environment in critical care requires a high
      level of collaboration among clinical team members and a sophisticated task
      coordination system to deliver safe, timely and effective care. A complex
      cognitive system underlies the decision-making process in such cooperative
      workplaces. This methodological review paper addresses the issues of translating
      cognitive research to clinical practice with a specific focus on decision-making
      in critical care, and the role of information and communication technology to aid
      in such decisions. Examples are drawn from studies of critical care in our own
      research laboratories. Critical care, in this paper, includes both intensive
      (inpatient) and emergency (outpatient) care. We define translational cognition as
      the research on basic and applied cognitive issues that contribute to our
      understanding of how information is stored, retrieved and used for problem
      solving and decision-making. The methods and findings are discussed in the
      context of constraints on decision-making in real-world complex environments and
      implications for supporting the design and evaluation of decision support tools
      for critical care health providers.

PMID- 18343732
TI  - Cyclin-dependent kinase inhibitor p16(INK4a) and telomerase may co-modulate
      endothelial progenitor cells senescence.
AB  - Endothelial cells (ECs) damage is an initial and pivotal step in the formation of
      atherosclerosis. Endothelial progenitor cells (EPCs), which have been considered
      as the precursor of ECs, can migrate and home to the site of injured ECs to
      divide into mature ECs and keep the integrity of the endothelial monolayer. It
      has been shown that the number and function of EPCs are negatively correlated
      with various atherosclerotic risk factors. This finding may be explained partly
      by accelerated senescence of EPCs induced by telomere attrition or shortening
      owning to oxidative stress and accumulative ROS. However, elevated telomerase
      activity which extends the telomere cannot lead to cellular immortal in the
      presence of the cyclin-dependent kinase inhibitor p16(INK4a). Researchers have
      the opinion that senescence is the balance between the regeneration and cancer.
      High expression of phosphorylated p16(INK4a), which is caused by oxidative stress
      and accumulative ROS, can prevent tumor cells from unlimited division and
      becoming malignant ones by accelerating premalignant cells premature senescence.
      It has been demonstrated that the expression of p16(INK4a) increases remarkably
      with age due to oxidative stress and accumulative ROS in some stem and progenitor
      cells, and regulates these cells age-dependent senescence. It is observed that
      telomeres shortening exists in these cells. Therefore, it can be hypothesized
      that p16(INK4a), together with telomerase, may co-modulate EPCs senescence.

PMID- 18343734
TI  - Purification of five azaspiracids from mussel samples contaminated with DSP
      toxins and azaspiracids.
AB  - Human intoxications during toxic episodes in shellfish are a very important
      concern for public health, as well as for economic interests of producer regions.
      Although initially each toxin appeared in a determined geographical zone,
      nowadays many of them are found in multiple places worldwide. In addition, more
      toxic compounds (new toxins or new analogs of known toxins) are being isolated
      and identified, which bring about new risks for public health. An example of this
      situation is the group of azaspiracids (AZAs). Initially these toxins were
      concentrated in Irish coasts but today appear in many different geographic
      locations; in the first toxic episode only three analogs were isolated, but now
      it is known that the group is comprised of at least eleven identified compounds.
      A substantial problem associated with all these new toxins is the extreme
      difficulty associated with the study of their toxic effects and mechanisms of
      action due to the very small quantities of purified toxin available. Therefore,
      the study of procedures to isolate them from contaminated shellfish or to
      synthesize them is of tremendous importance. In this paper we design a complete
      procedure to obtain AZAs analogs from mussels contaminated with DSP toxins and
      azaspiracids by means of three consecutive steps: an extraction procedure to
      remove toxins from shellfish, a solid phase extraction (SPE) to clean the samples
      and separate DSP toxins and AZAs, and a preparative HPLC to isolate each analog.
      In all the steps LC/MS is used to detect and quantify the toxins. Large amounts
      of AZA1, AZA2, AZA3, AZA4 and AZA5 were obtained by use of this procedure, which
      can be utilized in future studies relating to the toxins such as the production
      of certified materials and standards.

PMID- 18343735
TI  - A user's guide for serial excision.

PMID- 18343736
TI  - [Quinine-induced renal bilateral cortical necrosis].
AB  - Acute bilateral renal cortical necrosis is a rare cause of renal failure
      frequently induced by disseminated intravascular coagulation (Dic) following
      obstetrical complications, sepsis and drugs. We describe a case of Dic with
      bilateral cortical necrosis after ingestion of only one tablet of quinine. A 41
      year-old woman was admitted for severe abdominal pain, melaena, fever and anuria
      two hours after quinine tablet intake for nocturnal leg cramps. Her medical
      history included angioneurotic edema caused by chloroquine for malaria
      prevention. Physical examination was normal. Laboratory data showed acute renal
      failure, hemolytic anemia without schistocytes and Dic. Platelet antibodies were
      negative. Ultrasonographic examination showed a complete defect of renal
      perfusion with permeable renal arteries. Results of abdominal CT scan and MAG3
      scintigraphy led to the diagnosis of bilateral renal cortical necrosis. The
      patient underwent plasma exchanges with fresh frozen plasma which induced rapid
      resolution of Dic. She remained dependent on chronic hemodialysis. Quinine
      induced microangiopathic hemolytic anemia and Dic is a rare described entity.
      These complications occur typically in quinine-sensitized subjects. The presence
      of acute renal failure is generally associated with poor prognosis in case of
      bilateral renal cortical necrosis. Caution is required for the prescription of
      quinine derivates, which should be avoided in patients experienced on adverse
      reaction to the drug.

PMID- 18343737
TI  - Misconceptions - vitamin D insufficiency causes malabsorption of calcium.
AB  - The negative effect of vitamin D insufficiency on bone is commonly attributed to
      a decrease in calcium absorption although little evidence has been produced to
      support this assumption. Using two previously published series of elderly
      patients we refute this common assumption and present evidence that low
      circulating levels of 25 hydroxyvitamin D have a direct and deleterious effect on
      bone.

PMID- 18343738
TI  - The management of Clostridium difficile infection: antibiotics, probiotics and
      other strategies.
AB  - Clostridium difficile-associated disease remains an important nosocomial
      infection associated with significant morbidity and mortality. In recent years,
      there has been an upward trend in the incidence of this condition with continuing
      high rates of recurrent disease with available treatment regimens. In this
      article, we review the current literature on the management of C. difficile
      associated disease (CDAD). The potential role for alternative therapeutic options
      for the treatment of CDAD, including the use of bacteriotherapy in the form of
      probiotics, immunotherapy and ion-exchange resins as well as new drugs under
      investigation is explored. The evidence indicates a need for innovative
      approaches to the management of this condition. The combined use of antibiotic
      therapy and replacement of gut microbiota using probiotics remains promising and
      we suggest a multi-pronged approach in the management of this challenging
      infection.

PMID- 18343739
TI  - The impact of chemotherapy on overall survival and quality of life of patients
      with metastatic colorectal cancer: a review of phase III trials.
AB  - The treatment aims for advanced colorectal cancer (ACRC) patients are to prolong
      overall survival and to improve or maintain quality of life. Phase III studies
      published between 1997 and 2006 comparing different first or subsequent lines of
      treatment regimens were collected in order to evaluate the impact of these
      regimens on the overall survival and quality of life of ACRC patients. Our review
      shows that a first-line polychemotherapy regimen including oxaliplatin or
      irinotecan, in comparison with monochemotherapy, can improve overall survival.
      Second-line therapy and/or a cross-over between the first-line treatment arms can
      further modify the disease course. Hence, from the very beginning the treatment
      of ACRC patients must embrace a strategic approach taking into account all new
      agents available. Quality of life (QoL) was assessed in 52.3% of the first-line
      studies, while this was done in the whole group of studies evaluating pre-treated
      patients. QoL appears to be unrelated to the toxicity profile.

PMID- 18343740
TI  - Activity of daptomycin and selected antimicrobial agents tested against
      Staphylococcus aureus from patients with bloodstream infections hospitalized in
      European medical centers.
AB  - Daptomycin is a cyclic lipopeptide with potent bactericidal activity against Gram
      positive organisms and has been approved by the United States Food and Drug
      Administration for the treatment of Staphylococcus aureus bacteremia and
      infectious endocarditis (right-side). We evaluated the activity of daptomycin
      against bloodstream infection S. aureus strains from 4,799 patients hospitalized
      in 32 medical centers (12 European countries, Turkey and Israel) with bloodstream
      infections (BSI) during a 5-year period (2002-2006). Intravenous catheters were
      the source of infection in 15% of cases, and those strains were analyzed
      separately. All strains were susceptibility tested by reference broth
      microdilution methods utilizing calcium supplementation (50 mg/L) when testing
      daptomycin. Bactericidal activity of daptomycin and vancomycin were evaluated
      against a subset of 50 randomly selected strains. Daptomycin (MIC(50/90),
      0.25/0.5 mg/L), vancomycin (MIC (50/90), 1/1 mg/L), and linezolid (MIC(50/90),
      2/2 mg/L), were highly active (>99.9% susceptibility) against the strains
      evaluated; and daptomycin was the most potent (lowest MIC(90) ) among these
      compounds. Resistance rates to oxacillin and levofloxacin were generally
      elevated, especially when an intravenous catheter was the source of infection.

PMID- 18343741
TI  - Antimicrobial susceptibility profile of contemporary clinical strains of
      Stenotrophomonas maltophilia isolates: can moxifloxacin activity be predicted by
      levofloxacin MIC results?
AB  - The susceptibility profile of 763 Stenotrophomonas maltophilia isolates was
      evaluated against 16 antimicrobials by the CLSI reference broth microdilution
      method. Minocycline (MIC(90), 1 microg/ml; 100.0% susceptible) was the most
      active compound, followed by doxycycline (MIC(90), 4 microg/ml; 99.6%
      susceptible), trimethoprim/sulfamethoxazole (MIC(90), 1 microg/ml; 97.8%
      susceptible), and tigecycline (MIC(90), 2 microg/ml). An excellent correlation
      between levofloxacin (MIC(90), 4 microg/ml; 86.5% susceptible by published
      breakpoint criteria) and moxifloxacin (MIC(90), 2 micro g/ml) MIC results was
      observed indicating that moxifloxacin could be further evaluated as a therapeutic
      option for S. maltophilia infections.

PMID- 18343742
TI  - In vitro bactericidal activity of antibiotic combinations against clinical
      isolates of Mycobacterium chelonae.
AB  - Mycobacterium chelonae is one of the most antibiotic-resistant species of the
      pathogenic, rapidly-growing mycobacteria. The objective of this study was to
      evaluate the bactericidal activity of classical and new potential drugs, alone
      and in combinations, against clinical isolates of Mycobacterium chelonae.
      Clarithromycin was seen to be the most bactericidal drug. In drug combinations,
      this compound is most useful with gentamicin, fluoroquinolones, rifampicin,
      linezolid, other aminoglycosides, doxycyline and carbapenems. The combination of
      tobramycin with ciprofloxacin or moxifloxacin also exhibits similar activity. In
      conclusion, this study on bactericidal activity of drug combinations against
      Mycobacterium chelonae confirms the utility of clarithromycin associated with
      other drugs, and, of the new drugs, the value of moxifloxacin and linezolid.

PMID- 18343743
TI  - In vitro treatment with killed Helicobacter pylori downregulates the production
      of RANTES by peripheral blood mononuclear cells.
AB  - The mechanisms by which Helicobacter pylori colonizes and persists within the
      gastric mucosa are poorly understood. The gastric immune response observed in
      vivo during H. pylori infection, is characterized by a polarization of Th1 cell
      type that seems to be responsible for gastric pathology. The purpose of this
      study was to test the direct effect of H. pylori cagA(+)/vacA(+ )(live and/or
      gentamicin-killed) on human peripheral blood mononuclear cells (PBMCs) in order
      to evaluate the production of regulated activation normal T cell expressed and
      secreted (RANTES) in vitro. We also evaluated the possible relationship between
      RANTES release and the presence of IL-12 and IFN-gamma in supernatants of the
      same cells. In the present study, we show for the first time that the low amount
      of RANTES in supernatants of PBMC incubated with killed H. pylori is linked, at
      least in part, to the inhibition of IL-12 and IFN-gamma release.

PMID- 18343744
TI  - Comparison of the efficacy of tigecycline and teicoplanin in an experimental
      methicillin-resistant Staphylococcus aureus osteomyelitis model.
AB  - We evaluated the efficacy of tigecycline and teicoplanin in a rat model of MRSA
      osteomyelitis. Osteomyelitis was induced with an intramedullary injection of 10(8
      )colony-forming units (cfu) of MRSA. After osteomyelitis formation was confirmed
      on Day 14, infected rats were randomly divided into three groups: tigecycline
      (n=13), teicoplanin (n=13), and no-treatment control (n=14). A 28-day antibiotic
      therapy with a subcutaneous injection of tigecycline (14 mg/kg twice daily) or
      intramuscular administration of teicoplanin (20 mg/kg daily) was administered.
      Rats were then sacrificed, and the tibias were harvested. The bones were weighed
      and then cultured. Our results indicated that bacterial growth was significantly
      reduced in teicoplanin and tigecycline groups, compared to the control group
      (p=0.019 and p=0.006, respectively). However, no difference was detected between
      the two antibiotic groups (p=1.000). No bacterial growth was detected in 7 out of
      13 and 9 out of 13 specimens of the teicoplanin and tigecycline treated groups,
      respectively. Although this result was numerically in favor of tigecycline, the
      difference was not statistically significant (p=0.427). In conclusion,
      tigecycline, a novel antibiotic, appears as an effective alternative to
      teicoplanin in the treatment of osteomyelitis caused by MRSA.

PMID- 18343745
TI  - Comparison of rifampicin and moxifloxacin efficacy in an experimental model of
      animal brucellosis.
AB  - Brucellosis is an important health issue in many parts of the world and
      clinicians are still seeking for better treatment choices. The aim of this study
      was to investigate the efficacy of moxifloxacin in an experimental brucellosis
      model and to compare its activity with rifampicin. Wistar albino rats infected
      with Brucella abortus were then randomized into 3 groups, which received
      rifampicin, moxifloxacin, and tap water, respectively. After 21 days, they were
      sacrificed and spleen, liver and blood cultures were performed. Spleen and liver
      cultures of all the animals yielded B. abortus in the control group, while these
      rates were 20% and 20% in the rifampicin group and 50% and 40% in the
      moxifloxacin group, respectively. The blood culture positivity was 66% in the
      control group and 10% in the moxifloxacin group. Blood cultures were all negative
      in the rifampicin group. As a conclusion, moxifloxacin might be an alternative
      choice in the treatment of brucellosis.

PMID- 18343746
TI  - Immunomodulatory effect of three-day continuous administration of clarithromycin
      for experimental sepsis due to multidrug-resistant Pseudomonas aeruginosa.
AB  - Based on former animal studies showing the effect of clarithromycin in
      experimental sepsis by multidrug-resistant Pseudomonas aeruginosa following
      administration of single doses, the significance of its administration for three
      consecutive days was evaluated. Acute pyelonephritis was induced in 20 rabbits
      after inoculation of the test isolate in the renal pelvis. Therapy was
      administered upon signs of sepsis in group B; A served as control. Survival was
      recorded; monocytes were isolated for determination of ex vivo TNFalpha
      secretion. Quantitative cultures of organs were performed after death. Mean
      survival of groups A and B was 2.65 and 7.95 days respectively. At 24 hours,
      serum malondialdehyde of group B, which is an index of the oxidant status in
      serum, was lower than A. Ex vivo release of TNFalpha by the isolated monocytes of
      group B was lower than A at 3.5 and 48 hours. Tissue bacterial load was similar
      in two groups after animal death. It is concluded that clarithromycin possessed
      considerable immunomodulatory effects restraining release of TNFalpha from blood
      monocytes.

PMID- 18343747
TI  - A pharmacodynamic simulation to assess tigecycline efficacy for hospital-acquired
      pneumonia compared with other common intravenous antibiotics.
AB  - A pharmacodynamic model was used to generate supportive data comparing
      tigecycline with other broad-spectrum agents against pathogens implicated in
      hospital-acquired pneumonia (HAP). A 5000 patient Monte Carlo simulation
      determined the probability of target attainment (PTA) of tigecycline (+/-
      ceftazidime) compared with imipenem, levofloxacin, and piperacillin/tazobactam
      (+/- vancomycin). PTA was calculated over MICs of current Gram-positive and Gram
      negative bacteria collected from worldwide surveillance and weighted by the
      expected prevalence of these pathogens causing HAP. For monotherapy, the weighted
      PTA was imipenem (78.2%), piperacillin/tazobactam (73.3%), tigecycline (62.9%),
      and levofloxacin (62.5%). By pathogen PTA was greatest for tigecycline against
      Gram-positives, and ceftazidime or imipenem against Gram-negatives. Combination
      therapy increased PTA to 88.6%, 85.5%, 80.6%, and 69.8% for tigecycline,
      imipenem, piperacillin/tazobactam, and levofloxacin, respectively. Based on
      contemporary resistance data, tigecycline plus ceftazidime is predicted to
      achieve its pharmacodynamic targets similarly to combination therapy with
      imipenem plus vancomycin for the treatment of patients with HAP.

PMID- 18343748
TI  - Efficacy and safety of azithromycin 1 g once daily for 3 days in the treatment of
      community-acquired pneumonia: an open-label randomised comparison with
      amoxicillin-clavulanate 875/125 mg twice daily for 7 days.
AB  - This randomised, open-label, non-inferiority study was designed to demonstrate
      that a 3-day course of oral azithromycin 1 g once daily was at least as effective
      as a standard 7-day course of oral amoxicillin-clavulanate 875/125 mg twice daily
      in the treatment of outpatients with community-acquired pneumonia (Fine class I
      and II). In total, 267 patients with clinically and radiologically confirmed
      community-acquired pneumonia were randomly assigned to receive either the
      azithromycin (n=136) or the amoxicillin-clavulanate (n=131) regimen. At
      screening, 60/136 (58.8%) and 61/131 (62.9%) respectively had at least one
      pathogen identified by sputum culture, PCR, or serology. The primary endpoint was
      the clinical response in the intent-to-treat population at the end of therapy
      (day 8 to 12). Clinical success rates were 126/136 (92.6%) for azithromycin and
      122/131 (93.1%) for amoxicillin-clavulanate (treatment difference: - 0.48%; 95%
      confidence interval: - 5.66%; 4.69%). Clinical and radiological success rates at
      follow-up (day 22-26) were consistent with the end of therapy results, no patient
      reporting clinical relapse. Bacteriological success rates at the end of therapy
      were 32/35 (91.4%) for azithromycin and 30/33 (90.9%) for amoxicillin-clavulanate
      (treatment difference: 0.52%; 95% confidence interval - 10.81%; 11.85%). Both
      treatment regimens were well tolerated: the overall incidence of adverse events
      was 34/136 (25.0%) for azithromycin and 22/132 (16.7%) for amoxicillin
      clavulanate. In both treatment groups, the most commonly reported events were
      gastrointestinal symptoms. Azithromycin 1g once daily for 3 days is at least as
      effective as amoxicillin-clavulanate 875/125 mg twice daily for 7 days in the
      treatment of adult patients with community-acquired pneumonia.

PMID- 18343749
TI  - Comparison of disk diffusion, E-test and broth microdilution test in
      determination of susceptibility of Aspergillus species to amphotericin B,
      itraconazole and voriconazole.
AB  - In response to the recent increase in Aspergillus infections, new antifungal
      agents have become available accompanied by studies on antifungal susceptibility
      tests for epidemiological follow-up. The aim of this study was to compare the
      efficacy of Clinical Laboratory Standards Institute (CLSI) M 38-A broth
      microdilution test with the disk diffusion and E-test in determining the
      susceptibility of Aspergillus spp. to amphotericin B, itraconazole and
      voriconazole. The study was carried out on 18 A. fumigatus, 7 A. flavus, 5 A.
      niger and 2 A. versicolor strains isolated from clinical samples. The
      microdilution method was performed by following the instructions of CLSI M 38-A.
      The E-test and disk diffusion tests were performed according to the instructions
      of their manufacturers. The percent agreement between the E-test and CLSI M38-A
      broth microdilution test at 24 (48) h within +/- 2 dilutions was, respectively,
      81% (69%) for amphotericin B, 75% (72%) for itraconazole and 85% (81%) for
      voriconazole. The disk diffusion test showed good correlation with the E-test but
      poor correlation with the broth microdilution test for the three antifungal
      agents we tested. In conclusion, E-test and disk diffusion test have their
      advantages such as ease of application and interpretation, but their correlation
      with the broth microdilution should be improved.

PMID- 18343750
TI  - Impact of intravenous administration of voriconazole in critically ill patients
      with impaired renal function.
AB  - The administration of voriconazole by the intravenous (i.v.) route in patients
      with moderate or severe renal failure is limited because of potential toxic
      effects of the accumulation of the solvent vehicle sulphobutylether beta
      cyclodextrin sodium. This study aimed to assess the impact of intravenous
      voriconazole administration on renal and liver function in critically ill
      patients with impaired renal function treated with this antifungal drug. The
      study population consisted of a retrospective cohort of patients admitted to
      medical-surgical intensive care units (ICUs) who were treated with i.v.
      voriconazole for more than 3 days. Patients with impaired renal function were
      those with serum creatinine concentration >1.5 mg/dL, creatinine clearance <50
      mL/min, or under any extrarenal depuration procedure. Renal damage was defined as
      an increase of at least = 2 times initial serum creatinine level or starting of
      an extrarenal depuration procedure during voriconazole therapy. Liver damage was
      defined as an increase of = 4 times the initial serum concentration of liver
      enzymes, or = 2 times in patients with previous impaired liver function. A total
      of 69 patients was included in the study of which 26 (37.7%) had impaired renal
      function at the beginning of voriconazole treatment (serum creatinine >2.5 mg/dL
      in 10 patients). Mean (SD) duration of voriconazole treatment was 13.0 (9.5) days
      in patients with normal renal function and 11.2 (6.3) days in those with altered
      renal function. Renal damage during voriconazole therapy occurred in 13 (30.2%)
      patients with initial normal renal function and in 4 (15.4%) in patients with
      impaired renal function (P = 0.257). Liver damage during treatment with
      voriconazole was observed in 12 (27.9%) patients with normal initial renal
      function and in 3 (11.5%) patients with impaired renal function (P = 0.281).
      Renal failure developing during voriconazole treatment was associated with a
      significantly higher mortality rate (82.4% vs. 44.%, P = 0.01), except in the
      subgroup of patients with altered renal function before starting i.v.
      voriconazole (60% size=1>vs. 75%, P = 0.385). The use of i.v. voriconazole in ICU
      patients with pretreatment impaired renal function was not associated with renal
      or liver damage nor with an increase in ICU mortality.

PMID- 18343751
TI  - Effect of pegylated interferon treatments for chronic active hepatitis C on
      quality of life.
AB  - Health-related quality of life (HRQoL) during therapy was found to be improved in
      patients treated with peginterferon alpha-2a compared to patients receiving
      interferon alpha-2a. This study aimed to assess the effect of different pegylated
      interferon therapies used in the treatment of patients with chronic hepatitis C
      on HRQoL. Forty chronic hepatitis C patients were enrolled. 22 patients were
      given a combination of peginterferon alpha-2a plus ribavirin and 18 patients
      received a combination of peginterferon alpha-2b plus ribavirin for 48 weeks.
      Patients completed a Short Form-36 (SF-36) questionnaire at the start of
      treatment and at week 12, week 24 and week 48 of treatment and week 24
      posttreatment to evaluate HRQoL. In conclusion, the effect of both combination
      treatments on quality of life was similar.

PMID- 18343752
TI  - Differential expression of Glut 1 mRNA and protein levels correlates with
      increased sensitivity to the glyco-conjugated nitric oxide donor (2-glu-SNAP) in
      different tumor cell types.
AB  - Nitric Oxide (NO) releasing agents can serve as potent cytotoxic agents. However
      at present there are no effective ways to target delivery of NO donors like S
      nitroso-N-acetyl-penicillamine (SNAP). SNAP conjugated to glucose (2-gluSNAP) can
      be readily transported across the membrane by GLUT 1 transporters. Therefore,
      sensitivity of cells to 2-gluSNAP may depend on glucose-transporter GLUT 1. We
      evaluated the cytotoxicity of SNAP and 2-gluSNAP on a GLUT 1 rich glioblastoma
      cell line T98G and GLUT 1 deficient osteoblastoma cell line 143B and its
      mitochondria-deficient variant rhoo (cell line 206). The cytotoxity of SNAP and 2
      gluSNAP was assessed by clonogenic assay performed in the above cell lines in
      vitro. Immunoblotting and semi-quantitative real-time PCR assays were used to
      evaluate the expression of GLUT 1 transporter at protein and mRNA levels. The
      glioblastoma cell line T98G was more sensitive to 2-gluSNAP than unconjugated
      SNAP. SNAP and 2-gluSNAP affected the osteosarcoma cell lines 143B and rhoo
      poorly. Immunoblot analysis detected GLUT 1 protein in T98G cells and not in 143B
      or rhoo. There was about a 10-fold difference in GLUT 1 mRNA level in T98G cells
      compared to 143B and rhoo cell lines. This is consistent with our cytotoxicity
      studies and immunoblot analysis. Our results give credence to our hypothesis that
      the sensitivity to NO donors can be increased by glyco-conjugation and the
      cytotoxicity of the glyco-conjugated NO donors depends on the expression of GLUT
      1 mRNA and protein.

PMID- 18343753
TI  - Bendamustine--a new approach to the treatment of advanced hepatocellular
      carcinoma?
AB  - AIMS: Therapeutic options for advanced hepatocellular carcinoma (HCC) are
      limited. Bendamustine, a bifunctional cytostatic agent with mainly alkylating
      effect may be an alternative. METHODS: Five HCC cell lines were incubated in
      vitro with five different concentrations of bendamustine. In addition, cell lines
      Huh-7 and HepG2 were tested in a chimeric mouse model. RESULTS: In vitro
      treatment with bendamustine resulted in an IC( 50 )<6 microg/mL in two, <12
      microg/mL in one, and 12-23 microg/mL in two cell lines. In vivo, bendamustine
      reduced significantly tumor volume in chimeric mice. CONCLUSION: Bendamustine
      demonstrated significant tumor growth inhibition both in vitro and in vivo at
      concentrations that can be reached in the plasma. The potential role of
      bendamustine therapy for HCC and its tolerability in impaired liver function is
      currently subject of a phase II study.

PMID- 18343754
TI  - Biweekly triple combination chemotherapy with gemcitabine, oxaliplatin,
      levofolinic acid and 5-fluorouracil (GOLF) is a safe and active treatment for
      patients with inoperable pancreatic cancer.
AB  - GOLF is a triple translational combination chemotherapy regimen with gemcitabine,
      oxaliplatin, and 5-fluorouracil (5-FU) (plus levofolinic acid), cytotoxic drugs
      currently used in the treatment of pancreatic carcinoma. Considering its
      promising anti-tumor effects in patients with gastroenteric malignancies, we
      carried out the present study to investigate its toxicity and anti-tumor activity
      in patients with advanced pancreatic carcinoma. Twenty-seven patients were
      enrolled in the study, 15 males and 12 females with an average age of 61 years
      and a performance status (ECOG) </= 3. Eight of them had already received first
      line chemotherapy, 16 had liver involvement and 11 had inoperable locally (nodes,
      soft tissue infiltration, peritoneum etc) advanced disease. All patients received
      biweekly gemcitabine (1000 mg/m(2 )on day 1), oxaliplatin (85 mg/m(2 )on day 2);
      levofolinic acid (100 mg/m 2) and 5-FU (400 mg/m(2 )as bolus, and 800 mg/m(2 )in
      24-h infusion) on days 1 and 2. We report one fatal event occurring just after
      the first cycle due to lung embolism; grade II-III-diarrhea and mucosytis
      (44.4%); alopecia (37%); thrombocytopenia (18.5%); grade I-II asthenia, fatigue,
      non-neutropenic-fever (37%) and oxaliplatin-related neurotoxicity (18.5%). We
      also registered fast pain control in most patients, an objective response and
      disease control rate of 33.3% and 63% (1 complete and 8 partial responses and 8
      disease stabilizations) respectively, with clinical benefit in 60% of patients
      and median time to progression and overall survival of 5.5 and 8 months,
      respectively. In conclusion, the GOLF regimen appears to be a feasible treatment
      for patients with advanced pancreatic carcinoma that deserves to be evaluated in
      phase III trials.

PMID- 18343755
TI  - Capnocytophaga spp. DF-1 pneumonia in an immune-competent 56-year old man post
      CABG.
AB  - We report a case of a nosocomial Capnocytophaga spp. DF-1 pneumonia in an
      intubated 56-year-old man following coronary artery bypass grafting. We review
      Capnocytophaga spp., including the infections they produce and antibiotic
      susceptibilities.

PMID- 18343756
TI  - Characterization of extended-spectrum beta-lactamases in clinical isolates of
      Klebsiella pneumoniae and Escherichia coli from Posadas, Misiones, Argentina.

PMID- 18343757
TI  - Epidemiology of severe sepsis in Slovenian intensive care units for adults.

PMID- 18343758
TI  - In vitro interactions of approved and experimental drugs against Candida drugs
      against Candida spp.

PMID- 18343759
TI  - Prevention of cytomegalovirus reactivaction after allogenic hematopoietic stem
      cell transplantation with valganciclovir: single center experience.

PMID- 18343760
TI  - Urolithiasis under atazanavir boosted and tenofovir therapy: a case report.

PMID- 18343761
TI  - [Platelet aggregation inhibition in acute coronary syndrome. Facts and
      expectations].
AB  - The current practice of platelet aggregation inhibition in acute coronary
      syndrome is reviewed. The specific dosing and its clinical usefulness of each
      medication are considered. The author is drawing attention to the fact, that the
      dosing scheme used in the early phase 3 trials may not have been optimal as
      proven in later trials. The hyporeactivity against both acetylsalicylic acid and
      clopidogrel treatment is existing and maybe called resistance. Its clinical
      importance in clinical outcomes is to be determined in later investigations.
      Because of the probable relationship between resistance and clinical outcomes the
      measurement of platelet reactivity by a reliable rapid bedside tool may be
      important in the future. Also the new platelet aggregation inhibitors under
      development are reviewed.

PMID- 18343762
TI  - [Correlation between risk factors and mortality in elderly patients with femoral
      neck fracture with 5-year follow-up].
AB  - Hip fractures are associated with increased mortality in the elderly. There are
      only a few studies based on large patient number covering a nationwide health
      care system. AIM: The aim of this study was to investigate the mortality
      following primary treatment in patients over 60 with acute, monotraumatic femoral
      neck fracture on monthly and annual base during a 5-year follow-up period; and to
      evaluate the effect of different risk factors on mortality during the follow-up.
      METHODS: Data were derived from the nationwide database of the National Health
      Insurance Fund Administration. The evaluation includes patients with femoral neck
      fracture discharged from inpatient care institutions in 2000 following a primary
      surgical treatment. Weekly, monthly and annual mortality rates, and its monthly
      and annual trends according to risk factors were calculated. Logistic and Cox
      regression analysis was performed to evaluate the correlation between risk
      factors and mortality. RESULTS: 3783 patients were involved in the study with a
      mean age of 77,97 years (SD 8,52). The mortality rates were 1,71% (during the
      first week), 8,99% (30 days), 30,74% (first year) and 61,88% (in 5 years).
      Mortality showed a declining trend up to the 5th month, and is stagnant after the
      first year. Risk factor analysis showed that higher risk of mortality is
      associated with male sex and higher age group up to 5 years, co-morbidities up to
      4 years, lateral type femoral neck fracture and 12 hours delay of primary
      treatment up to 2 years, early local complications up to 1 year and surgical
      treatment during week-end up to 1 month. Surgical treatment delivered in national
      health institutes and university clinics resulted in a lower mortality risk up to
      1 year. CONCLUSIONS: In order to reduce mortality during the management of hip
      fractures, the authors emphasize the importance of delay of treatment within 12
      hours, appropriate selection of methods corresponding to fracture type, providing
      the same conditions for primary treatment during all days of the week, to
      organize the treatment to special centres, appropriate acute care and follow-up
      corresponding to the general health status and co-morbidities of patients.

PMID- 18343763
TI  - [Crohn's disease of the duodenum. Clinical signs, diagnosis, conservative and
      surgical treatment].
AB  - Duodenal localization of Crohn's disease is rare, accounting for only 0.5-4% of
      all cases. Most common complaints are gastric outlet obstruction and weight loss.
      Histologic findings of endoscopic biopsy are frequently not definitive, making
      differentiation from other, benign structures complicated. There are also no
      standard guidelines regarding indications for surgical management. PATIENTS AND
      METHODS: We reviewed the cases of three surgically managed patients with duodenal
      Crohn's disease at the 1st Department of Surgery, Semmelweis University of
      Medicine, Budapest, during a 5-year period (2002-2007). All three patients had
      persistent symptoms of stomach emptying disorder despite medical therapy and had
      severe weight loss (13-30 kg). In two cases resection of the stenotic duodenum
      was performed successfully using Billroth II method. Gastro-jejunal bypass was
      performed in one case, where the descendent duodenum was inflamed. RESULTS: All
      patients have been asymptomatic since surgery (9-45 months of follow-up) and
      recovered their earlier bodyweight. The postoperative period was uneventful.
      CONCLUSIONS: There is indication of surgery in cases of stenosing duodenal
      Crohn's disease, when medical therapy is not successful, but long-standing
      malnutrition should be treated preoperatively. We found perioperative morbidity
      to be similar in patients with duodenal Crohn's and in those with Crohn's disease
      of other intestinal locations.

PMID- 18343764
TI  - [Investigation of redox homeostasis in liver and renal transplant recipients].
AB  - The time course of free radical reactions is evaluated by the authors. Within
      pretransplant patients as of their poorly functioning metabolism free radical
      overproduction may be observed, hence their antioxidant capacity decreases. When
      the graft is functioning well, the free radical-antioxidant balance of
      homeostasis is reestablished. During the early postoperative period, when
      symptoms (acute rejection, infection, acute tubular necrosis, cholestasis)
      appear, free radical reactions increase. The authors demonstrate, this is
      strengthened by the fact that the mediator [interleukin-6 (IL-6), C-reactive
      protein, serum amyloid-A], and enzyme levels that take part in the free radical
      processes rise. The monitoring of these parameters during the early postoperative
      period is a good early indicator for acute rejection and for the effect of
      therapy. During acute rejection just as during infection most of these parameters
      increased significantly compared to the healthy control. They show the activation
      of the immune system but they are not useful for differential diagnosis, with the
      exception of IL-6 which we measured in larger quantities during bacterial
      infection but not so in acute rejection. For the prediction of early renal graft
      function we used urinary enzyme levels (dipeptidyl-aminopeptidase, glutathione-S
      transferase). Tissue damage is followed by enzyme increasing and antioxidant
      capacity depletion. With choosing of adequate tests, the perioperative redox
      homeostasis of the transplanted patients can be monitored and with dosing the
      antioxidants the uncontrolled forming of reactive oxygen metabolites can also be
      decreased and checked.

PMID- 18343765
TI  - [Intrafamilial hepatitis C virus infection].
AB  - The role of blood and other biological fluids in transmission of HCV is already
      proven. The infection is acquired mainly by uncontrolled transfusion of blood
      products, percutaneous inoculation by contaminated equipment, mother-to-infant as
      well as sexual exposures. Infection by common contact in the family is very rare,
      but data are present in the literature. AIM: The authors demonstrate a clinical
      case of possible intrafamilial spread of hepatitis C virus. CASE REPORT: Forty
      seven-year-old woman with chronic hepatitis C has one anti-HCV positive daughter.
      DISCUSSION: Because of the long period of incubation, less specific symptoms of
      acute C-hepatitis and often development of symptom-free disease, the patients and
      their families can be long in living together without being unaware of potential
      infection. CONCLUSION: Intrafamilial spread of hepatitis C virus may occur. It is
      strongly suggested to inform the patients about the possible risk and the
      importance of personal hygiene.

PMID- 18343766
TI  - [Benign prostatic hyperplasia].

PMID- 18343767
TI  - ["Without empathy one cannot be a good physician!" Interview with dr. Laszlo
      Romics].

PMID- 18343769
TI  - [Autologous bone marrow-derived stem cell therapy in patients with severe
      peripheral arterial disorder].
AB  - BACKGROUND AND AIMS: Amputation is the only current option for relief of rest
      pain or gangrene in patients with severe peripheral arterial disease. Up to now,
      no effective blood-flow enhancement therapies are available. Autologous bone
      marrow-derived stem cell transplantation is an arising therapy modality with an
      option of building new blood vessels through endothelial stem and/or progenitor
      cells. PATIENTS AND METHODS: Five patients with severe peripheral arterial
      disorder were treated by autologous bone marrow-derived stem cell therapy. CD34+,
      CD133+ and CD45+/- cell number and ratio were determined. CD34+ cells were
      isolated by magnetic separation and collected into a 10 ml sample. The cell
      suspension was administered by local intramuscular injections (0.5-1.0 ml
      injections in the musculus gastrocnemius). The follow-up (before; 1, 3, 6, 9 and
      12 months after the autologous bone marrow-derived stem cell therapy) based on
      clinical (rest pain, walking distance without pain, changes of non-healing
      ischaemic ulcers, ankle-brachial index) and laboratory (angiography, Color- and
      Laser-Doppler scan, measurement of transcutaneous oxygen tension and endothelial
      function test) parameters was documented and analyzed. RESULTS: Improvement of
      pain and walking distance was observed in all five cases. In three cases the non
      healing ischaemic ulcers disappeared, in one other case they became smaller and
      thinner, and in one case no change was realized. The average of ankle-brachial
      index improved significantly (before: 0.41, twelve months after: 0.83). New
      collaterals were detected by angiography in three patients, but duplex
      ultrasonography detected improvement in one patient only. Before and 1, 6 and 12
      months after stem cell therapy the transcutaneous oxygen tension changed on the
      foot from 18.80/16.78/23.83/37.50 mmHg, and on the calf from
      36.66/31.25/45.00/37.30 mmHg. The macro- and microcirculation parameters did not
      show improvement after 1 month, however, after 3, 6, 9 and 12 months improved
      parameters were recorded. Severe adverse events were not observed. In one case
      elevated level of serum creatinine phosphokinase, and in another case a mild form
      of vasculitis were detected. CONCLUSION: autologous bone marrow-derived stem cell
      therapy with isolated CD34+ cells is effective, safe and results in sustained
      clinical benefit for patients with severe peripheral arterial disease.

PMID- 18343770
TI  - [Epidemiology, risk factors and molecular pathogenesis of primary liver cancer].
AB  - Primary liver cancer is the fifth most common cancer worldwide. Hepatocellular
      carcinoma accounts for 85-90% of primary liver cancers. Distribution of
      hepatocellular carcinoma shows variations among geographic regions and ethnic
      groups. Males have higher liver cancer rates than females. Hepatocellular
      carcinoma occurs within an established background of chronic liver disease and
      cirrhosis (70-90%). Major causes (80%) of hepatocellular carcinoma are hepatitis
      B, C virus infection, and aflatoxin exposition. Its development is a multistep
      process. We have a growing understanding on the molecular pathogenesis. Genetic
      and epigenetic changes activate oncogenes, inhibit tumorsuppressor genes, which
      result in autonomous cell proliferation. The chromosomal instability caused by
      telomere dysfunction, the growth-retrained environment and the alterations of the
      micro- and macroenvironment help the expansion of the malignant cells.
      Understanding the molecular mechanisms could improve the screening of patients
      with chronic liver disease, or cirrhosis, and the prevention as well as treatment
      of hepatocellular carcinoma.

PMID- 18343771
TI  - [Cytomegalovirus infection after solid-organ transplantation, its risk factors,
      direct and indirect effects and prevention strategies].
AB  - The human cytomegalovirus is widely prevalent among human population and it is
      the most common viral pathogen that affects both the graft's and solid-organ
      transplant recipient's survival. The risk is highest in donor-seropositive,
      recipient-seronegative pairing transplantation. These recipients carry increased
      risk of developing symptomatic primary CMV infection; however, other risk factors
      may have an impact on cytomegalovirus activation as well: intensity of
      immunosuppression, type of organ transplanted, rejection and/or treatment for
      rejection, HLA-mismatch between recipient and donor, certain HLA-types of the
      recipient, female sex etc. Cytomegalovirus infection in transplant patients has
      been associated with both direct (symptoms) and indirect effects which are
      derived from the immunomodulating impact of the virus such as cellular effects
      and cytokine expression or systemic immune suppression leading to other
      opportunistic infections. Prevention of the direct and indirect effects of
      cytomegalovirus infection is the therapeutic goal in transplanted patients. Most
      transplant centers use either universal prophylaxis or preemptive therapy to
      prevent the infection. The advantages and disadvantages of these two preventive
      strategies and current evidence-based recommendations for preventing
      cytomegalovirus disease in solid-organ transplant recipients are discussed
      according to others' and the authors' own observations. According to
      recommendations of the American and Canadian Societies of Transplantation, most
      of the centers--after analyzing of the CMV-infection risk factors of the
      recipients--divide them into three groups: high-, moderate- and low-risk groups.
      The preventive strategy is attached to the risk-group type. In the high-risk
      group (R-/D+ and lung transplant patients) the use of the universal prophylaxis
      is necessary. The patients administered anti-lymphocyte antibodies (ATG, ALG or
      OKT3) need selective (subtype of universal) prophylaxis. Among the moderate-risk
      patients (R+/D+ or R+/D-) the doctors may choose either universal prophylaxis or
      preemptive therapy. Selection of a strategy requires consideration of patient
      specific factors as well as practical considerations such as available resources.
      For avoidance of the indirect effects of CMV infection universal prophylaxis is
      preferred. The use of preventive proceedings in low-risk patients is the matter
      of the center's decision.

PMID- 18343772
TI  - [Urethral stenosis].

PMID- 18343773
TI  - [Anthropology of the breast].

PMID- 18343774
TI  - [Physicians' names in the language].

PMID- 18343776
TI  - Visualization of growth signal transduction cascades in living cells with
      genetically encoded probes based on Forster resonance energy transfer.
AB  - Fluorescence probes based on the principle of Forster resonance energy transfer
      (FRET) have shed new light on our understanding of signal transduction cascades.
      Among them, unimolecular FRET probes containing fluorescence proteins are rapidly
      increasing in number because these genetically encoded probes can be easily
      loaded into living cells and allow simple acquisition of FRET images. We have
      developed probes for small GTPases, tyrosine kinases, serine-threonine kinases
      and phosphoinositides. Images obtained with these probes have revealed that
      membrane protrusions such as nascent lamellipodia or neurites provide an active
      signalling platform in the growth factor-stimulated cells.

PMID- 18343777
TI  - Cytotechnologists today: much more than "pap-ologists" with schools in need of
      our support.

PMID- 18343778
TI  - CSF multianalyte profile distinguishes Alzheimer and Parkinson diseases.
AB  - The therapeutic imperative for Alzheimer disease (AD) and Parkinson disease (PD)
      calls for discovery and validation of biomarkers. Increased cerebrospinal fluid
      (CSF) tau and decreased amyloid (A) beta42 have been validated as biomarkers of
      AD. In contrast, there is no validated CSF biomarker for PD. We validated our
      proteomics-discovered multianalyte profile (MAP) in CSF from 95 control subjects,
      48 patients with probable AD, and 40 patients with probable PD. An optimal 8
      member MAP agreed with expert diagnosis for 90 control subjects (95%), 36
      patients with probable AD (75%), and 38 patients with probable PD (95%). This MAP
      consisted of the following (in decreasing order of contribution): tau, brain
      derived neurotrophic factor, interleukin 8, Abeta42, beta2-microglobulin, vitamin
      D binding protein, apolipoprotein (apo) AII, and apoE. This first large-scale
      validation of a proteomic-discovered MAP suggests a panel of 8 CSF proteins that
      are highly effective at identifying PD and moderately effective at identifying
      AD.

PMID- 18343779
TI  - High-sensitivity tandem mass spectrometry assay for serum estrone and estradiol.
AB  - High-sensitivity measurement of serum estrogens is important in adult and
      pediatric endocrinology and oncology. We developed a high-sensitivity liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) assay for simultaneous
      measurement of estrone (E1) and estradiol (E2). Aliquots of 200 muL of serum were
      spiked with internal standard, extracted, derivatized with dansyl chloride, and
      analyzed by LC-MS/MS using 2-dimensional chromatographic separation. Total
      imprecision for the method was less than 11%; the limit of quantitation was 1
      pg/mL. Reference intervals were established with samples from more than 900
      healthy postmenopausal women, men, girls, and boys. Concentrations of estrogens
      in children reached adult levels by Tanner stage 3. In men and postmenopausal
      women, the median concentrations of total estrogens (E1 + E2) were 39 and 22
      pg/mL, and the median E2/E1 ratios were 0.98 and 0.55, respectively. The method
      requires a small sample volume and has adequate sensitivity and specificity for
      analyzing estrogens in samples from postmenopausal women, men, and children.

PMID- 18343780
TI  - Analytic bias among certified methods for the measurement of hemoglobin A1c: a
      cause for concern?
AB  - We studied the magnitude, significance, and origin of an analytic bias that
      emerged between our point-of-care (POC) and our central laboratory (CL) methods
      for the measurement of hemoglobin A1c (HbA1c) and evaluated the analytic accuracy
      of 7 commonly used HbA1c methods relative to the National Glycohemoglobin
      Standardization Program (NGSP) reference method. The POC and CL methods were
      compared by split-sample analysis of clinical specimens and time series analyses
      of the HbA1c results reported for a 33-month period. The relative accuracies of 7
      HbA1c methods were evaluated using College of American Pathologists proficiency
      survey results. Long-term drifts in the CL- and POC-analyzed test results caused
      the median intermethod bias [(POC result)-(CL result)] to increase from -0.4% to 
      0.9% HbA1c. Systematic biases, drifts in analytic performance over time, and
      intermethod variability were frequently observed among the 7 NGSP-certified HbA1c
      methods. Intermethod variability is a potential source of inaccuracy whenever
      HbA1c results are interpreted relative to universal, fixed, clinical decision
      thresholds.

PMID- 18343781
TI  - Rapid detection of oleander poisoning by Digoxin III, a new Digoxin assay: impact
      on serum Digoxin measurement.
AB  - We studied the potential for detecting oleander with a new immunoassay (Digoxin
      III, Abbott Laboratories, Abbott Park, IL) by comparing results with those from
      the fluorescence polarization immunoassay (FPIA) and Digoxin II assay (Abbott).
      In aliquots of drug-free serum pools supplemented with pure oleandrin or oleander
      extract, we observed apparent digoxin values using all 3 immunoassays, but values
      obtained by the Digoxin III were higher than obtained by the other assays. We
      also observed significant apparent digoxin values in vivo in serum samples of
      mice 1 and 2 hours after feeding oleander extract. The average half-life of
      digoxin-like factors was 1.1 hours. In a serum pool (prepared from patients
      taking digoxin) supplemented with oleander extract, the observed digoxin values
      were falsely lowered when measured by the Digoxin II but falsely elevated when
      measured by the Digoxin III and FPIA. Monitoring free digoxin using the Digoxin
      III cannot eliminate this interference. Digibind neutralized digoxin-like factors
      of oleander extract; the effect can be monitored by observing a significant
      reduction in apparent free digoxin levels in the presence of Digibind as measured
      in protein-free ultrafiltrate using the Digoxin III. The Digoxin III is highly
      sensitive for measuring oleander.

PMID- 18343782
TI  - PAX-5 expression in pulmonary neuroendocrine neoplasms: its usefulness in
      surgical and fine-needle aspiration biopsy specimens.
AB  - The World Health Organization classification of lung tumors recognizes 4
      histologic subtypes of pulmonary neuroendocrine carcinomas (NECs), which include
      typical carcinoids (TCs), atypical carcinoids (ACs), small cell carcinomas
      (SCCs), and large cell NECs (LCNECs). These tumors can be misclassified owing to
      morphologic parallels, indicating the necessity for adjunctive tests for correct
      classification. We evaluated immunohistochemical expression of PAX-5 in
      histologic and fine-needle aspiration (FNA) specimens of pulmonary NECs. Staining
      was stratified by intensity (0 to 3+) and percentage of cells stained as focal
      (<10%) or diffuse (=10%). PAX-5 expression was present in 29/37 (78%) of high
      grade NECs (22/26 SCCs, 1/2 LCNECs, and 6/9 combined tumors) and none of 51 TCs
      and ACs; FNA specimens showed concordant staining. This study confirmed that PAX
      5 is a useful marker in FNA and surgical specimens for the discrimination of low-
      to intermediate-grade NECs from high-grade NECs with 100% specificity and 79%
      sensitivity in surgical specimens.

PMID- 18343783
TI  - Quantitative PCR and HER2 testing in breast cancer: a technical and cost
      effectiveness analysis.
AB  - We performed a technical and cost-effectiveness analysis of quantitative reverse
      transcription-polymerase chain reaction (Q-RT-PCR) for the assessment of HER2 in
      breast cancer. We evaluated 44 frozen and 55 formalin-fixed paraffin-embedded
      (FFPE) breast carcinoma specimens by Q-RT-PCR, immunohistochemical analysis, and
      fluorescent in situ hybridization (FISH). Immunohistochemical and FISH analyses
      were performed on individual slides and on tissue microarray. Costs of techniques
      were calculated to study 1 case and 10 or 40 cases. Q-RT-PCR provided reliable
      data in frozen and FFPE specimens, which were significantly correlated. HER2
      messenger RNA levels were significantly stratified in agreement with
      immunohistochemical data (P < .05). There was complete concordance between Q-RT
      PCR and immunohistochemical results for negative and strongly positive (3+)
      cases. The intermediate immunohistochemical group (2+), including FISH+ and FISH-
      cancers, could also be stratified by Q-RT-PCR. Cost analysis documented the
      advantage of Q-RT-PCR in all US Food and Drug Administration-approved assays. Our
      data support the use of Q-RT-PCR for testing breast cancer specimens to select
      patients for HER2 inhibitory therapy.

PMID- 18343784
TI  - CDX2 and villin are useful markers of intestinal metaplasia in the diagnosis of
      Barrett esophagus.
AB  - The identification of intestinal metaplasia (IM) in the esophagus is necessary
      for the selection of patients with Barrett esophagus (BE) for surveillance. We
      studied 108 esophageal biopsy and resection specimens, clinically diagnosed as
      BE, and stained them for CDX2, villin, HepPar-1, and cytokeratin (CK) 7 to
      investigate sensitivity for identifying IM. H&E-stained sections showed definite
      goblet cells in 94 cases. CDX2 and villin were positive in all 94 cases. Of 38
      cardia- and 9 fundic-type mucosa samples associated with BE, 13 (34%) and 0 (0%)
      displayed CDX2 positivity and 21 (55%) and 1 (11%) displayed villin positivity,
      respectively. HepPar-1 was positive in 54 (57%) of 94 cases with IM and negative
      in the associated cardia- and fundic-type mucosa. A full-thickness CK7 staining
      pattern was present in 90 (96%) of samples with IM and 22 (58%) and 0 (0%) of the
      associated cardia- and fundic-type mucosa, respectively. None of 20 control
      samples of morphologically normal gastric mucosa stained for CDX2 or villin. CDX2
      and villin are sensitive markers for early-stage IM and can supplement the
      histologic identification of this premalignant condition in the esophagus.

PMID- 18343785
TI  - Prognostic significance of intratumoral and peritumoral lymphatic density and
      blood vessel density in invasive breast carcinomas.
AB  - We studied tumor lymphatic and vascular densities and lymphovascular invasion
      (LVI) as prognostic markers in 48 cases of invasive breast cancer treated with
      partial or total mastectomy and lymph node dissection. All cases were
      immunostained with D2-40 and CD31. Positively stained microvessels were counted
      in densely vascular/lymphatic foci (hot spots) at x400. The mean+/-SD peritumoral
      lymphatic microvessel density (LMD) was significantly higher than intratumoral
      LMD (9+/-7 vs 4+/-6; P< .01). There was a positive correlation of D2-40 LMD
      (peritumoral and intratumoral) and CD31 microvessel density counts with lymph
      node metastasis (r=0.35, 0.5, and 0.38), nuclear grade (r=0.36, 0.28, and 0.3),
      and stage (r=0.42, 0.56, and 0.49), respectively. Peritumoral and intratumoral D2
      40 LMD correlated significantly with the presence of angiolymphatic invasion
      (detected by D2-40; r=0.54 and 0.54, respectively). D2-40 detected more LVI than
      H&E- and CD31-detectable vascular invasion (18/48, 5/48, 11/48, respectively).
      Increased D2-40 detected LVI, and high CD31 microvessel counts showed significant
      adverse effect on survival status.

PMID- 18343786
TI  - Measurements of global cell-mediated immunity in renal transplant recipients with
      BK virus reactivation.
AB  - The Cylex ImmuKnow Test (Cylex, Columbia, MD) measures immune cell function (ICF)
      and is based on the amount of adenosine triphosphate (ATP) released when T cells
      are stimulated by phytohemagglutinin. This preliminary study sought to determine
      if ICF measurements can be used to stratify kidney transplant recipients
      according to the risk for developing BK virus infection. ICF measurements were
      done in 15 samples from 8 patients with BK viremia, 38 samples from 25 patients
      with BK viruria, and 243 samples from 148 patients with no BK viruria or viremia.
      The mean+/-SD amounts of ATP released in these 3 groups were 102.9+/-58.6,
      227.2+/-146.4, and 231.8+/-150.8 ng/mL, respectively (P= .002, viremia vs all
      other samples). Within the viruria group, lower ICF values were associated with
      higher urinary viral load (P= .037). These results show that a decreased ICF test
      result correlates with active viral replication in kidney transplant recipients.

PMID- 18343787
TI  - Immunohistochemical detection of the von Hippel-Lindau gene product (pVHL) in
      human tissues and tumors: a useful marker for metastatic renal cell carcinoma and
      clear cell carcinoma of the ovary and uterus.
AB  - Genetic alteration of the von Hippel-Lindau (VHL) tumor suppressor gene has been
      linked to hereditary and sporadic clear cell renal cell carcinomas (RCCs).
      Inconsistent data on immunodetection of the VHL gene product (pVHL) in normal
      tissues and tumors have been reported. We immunohistochemically reevaluated the
      usefulness of a specific rabbit polyclonal anti-pVHL antibody in 531 cases of
      renal and nonrenal neoplasms and normal tissues. Positive immunostaining was
      observed in nearly 100% of primary renal neoplasms, 95% of metastatic RCCs, and
      90% of clear cell carcinomas of the ovary and uterus. In normal tissues, positive
      immunoreactivity was observed only in renal tubules, exocrine pancreas, islets,
      and bile ducts. Western blot and reverse transcription-polymerase chain reaction
      confirmed the immunostaining results. These data indicate that this anti-pVHL
      antibody is a useful marker in assisting diagnosis of metastatic RCC and may
      serve as a diagnostic marker for clear cell carcinomas of the ovary and uterus.

PMID- 18343788
TI  - Clinical role of p16INK4a expression in liquid-based cervical cytology:
      correlation with HPV testing and histologic diagnosis.
AB  - p16INK4a is overexpressed in high-risk human papillomavirus (HR-HPV)-infected
      preneoplastic and neoplastic lesions of the uterine cervix. Our aim was to verify
      whether p16 is a diagnostic marker also in cervical liquid-based cytology. We
      performed p16 immunocytochemical analysis and the Hybrid Capture 2 (HC2) test
      (Digene, Gaithersburg, MD) for HR-HPV infection in 471 ThinPrep-processed (Cytyc,
      Boxborough, MA) cervicovaginal samples and correlated the results with histologic
      findings. A total of 32.3% of the specimens showed p16 immunoreactivity, whereas
      the HC2 test was positive in 41.2% of the cases (65.2% concordance rate).
      Correlating the cytologic, p16, and HPV results with histologic findings revealed
      HC2 as the most sensitive test for a diagnosis of cervical intraepithelial
      neoplasia 2 or worse, whereas cytologic examination was the most specific. The
      positive predictive value was significantly higher for cytologic examination than
      for p16 and HR-HPV testing. These data suggest that p16 evaluation in ThinPrep
      samples does not have better clinical effectiveness for identifying high-grade
      lesions than conventional morphologic examination and HPV testing.

PMID- 18343789
TI  - Clinicopathologic implications of genetic instability in intestinal-type gastric
      cancer and intestinal metaplasia as a precancerous lesion: proof of field
      cancerization in the stomach.
AB  - To clarify field cancerization in the stomach by genetic alterations, we studied
      83 cases of intestinal-type gastric cancer (GC) and paired intestinal metaplasia
      (IM) distant from GC and 39 cases of chronic gastritis with IM (CG-IM) for
      genetic instability (GIN). Microsatellite instability (MSI) and loss of
      heterozygosity (LOH) were evaluated at 5 microsatellite loci. The incidence of
      GIN was 21% (8/39) in CG-IM, 48% (40/83) in GC-IM, and 65% (54/83) in GC and
      showed a significant difference among these 3 categories. By tumor location, MSI
      showed the highest incidence in GC and GC-IM with the tumor located in the upper
      third of the stomach. GIN in GC and GC-IM significantly increased with the
      progression of tumor invasion from mucosal to advanced cancer. GIN, especially
      LOH, was more frequently detected in cases with vs without lymphatic or vascular
      invasion and lymph node involvement in GC and GC-IM. The GIN of GC and GC-IM was
      significantly similar in relation to clinicopathologic features. Biologic
      detection of GIN in IM may be a surrogate marker for GC risk and for clinical
      evaluation of malignant potential. The condition is consistent with the
      hypothesis of field cancerization in the stomach.

PMID- 18343790
TI  - Aberrant expression of CD7 in myeloblasts is highly associated with de novo acute
      myeloid leukemias with FLT3/ITD mutation.
AB  - Acute myeloid leukemia (AML) with normal cytogenetics represents approximately
      40% to 50% of de novo AML. This heterogeneous AML subgroup constitutes the single
      largest cytogenetic group with an intermediate prognosis. Previous studies have
      suggested that the Fms-like tyrosine kinase-3 internal tandem duplication
      (FLT3/ITD) mutation-positive de novo AML may represent a distinctive subgroup of
      AML. We analyzed the clinical and pathologic features of 15 cases of de novo AML
      with normal cytogenetics and with the FLT3/ITD mutation. In comparison with
      patients with AML without the FLT3/ITD mutation, patients with FLT3/ITD+ AML are
      relatively younger, more often have marked peripheral leukocytosis with a higher
      number of circulating blasts at initial examination, more often have minimal
      differentiation morphologic features, more frequently have abnormal CD7
      coexpression, and have poorer outcome. Close association of aberrant CD7
      expression and FLT3/ITD mutation in the myeloblasts of FLT3/ITD+ AML suggests
      that FLT3/ITD- mediated leukemic transformation occurs in the more early stage of
      myeloid progenitor cells.

PMID- 18343791
TI  - A subset of CD5- diffuse large B-cell lymphomas expresses nuclear cyclin D1 with
      aberrations at the CCND1 locus.
AB  - In 231 diffuse large B-cell lymphomas, the expression of cyclin D1 and CD5 was
      evaluated. All cases were CD5-. Ten (4.3%) were positive for cyclin D1 and were
      subjected to fluorescence in situ hybridization at the CCND1 locus. One case
      showed the t(11;14). In another case, the telomeric probe signal for cyclin D1
      was lost in most tumor cells, and in a small proportion of the cells, there were
      fluorescence signals indicative of the t(11;14). Two other cases displayed
      additional cyclin D1 signals in the absence of the t(11;14). All cases but 1 were
      positive for bcl-6 or MUM1, disfavoring the possibility of misdiagnosed blastoid
      variants of CD5- mantle cell lymphomas. Thus, contrary to the current view, there
      seems to exist a certain number of cyclin D1+ and CD5- diffuse large B-cell
      lymphomas, some of which have structural aberrations at the CCND1 locus,
      including the t(11;14).

PMID- 18343792
TI  - Sudden extramedullary T-lymphoblastic blast crisis in chronic myelogenous
      leukemia: a nonrandom event associated with imatinib?
AB  - Imatinib has dramatically altered the natural history of chronic myelogenous
      leukemia (CML), with the majority of patients now experiencing long-term
      remission and improved survival. However, in addition to the well-described
      phenomenon of resistance to imatinib, typically due to point mutations, uncommon
      consequences (eg, the development of Philadelphia chromosome-negative clones) may
      infrequently occur. We report 2 cases of sudden BCR/ABL1+ blast crisis in
      patients with CML who had achieved complete hematologic remission with imatinib
      therapy but were obligated to discontinue therapy owing to pancytopenia. These
      sudden blast crises were unusual at 3 levels: first, they were of precursor T
      lymphoblastic lineage; second, they had a primary extranodal presentation without
      overt bone marrow involvement; and third, they developed after recent cessation
      of imatinib. These observations suggest that the occurrence of 2 such rare cases
      in a single institution within a 1-year time frame may reflect another unusual
      consequence of imatinib therapy.

PMID- 18343793
TI  - Circulating PSA-containing macrophages as a possible target for the detection of
      prostate cancer: a three-color/five-parameter flow cytometric study on peripheral
      blood samples.
AB  - A major problem of serum prostate-specific antigen (PSA) for predicting prostate
      cancer risk is diagnostic uncertainty. To detect circulating macrophages with
      phagocytized fragments (eg, PSA) of prostate tumor cells and determine if the
      number of circulating PSA-containing macrophages can help differentiate between
      benign and malignant prostate disease, we collected mononuclear cells from
      peripheral blood. After labeling the macrophages, phagocytized PSA was detected
      by incubating the cells with a phycoerythrin-conjugated PSA monoclonal antibody.
      Flow cytometric analysis was performed. A significant difference was observed in
      the mean+/-SD percentage of activated macrophages (CD14+/CD16+) between malignant
      (28.8%+/-13.0%) and benign conditions (17.3%+/-6.8%; P< .0001). A significant
      increase was detected in the percentage of PSA-containing macrophages in prostate
      cancer (17.7%+/-12.3%) vs benign disorders (3.6%+/-1.9%; P< .0001) and between
      localized (10.5%+/-3.4%) and metastasized prostate carcinoma (26.3%+/-14.3%; P=
      .0002). The new method for detecting circulating PSA-containing macrophages can
      be suitable for differentiating prostate cancer from benign conditions and,
      possibly, low-risk from more aggressive prostate cancer.

PMID- 18343794
TI  - Evaluation of influenza prevention in the workplace using a personally controlled
      health record: randomized controlled trial.
AB  - BACKGROUND: Personally controlled health records (PCHRs) are accessible over the
      Internet and allow individuals to maintain and manage a secure copy of their
      medical data. These records provide a new opportunity to provide customized
      health recommendations to individuals based on their record content. Health
      promotion programs using PCHRs can potentially be used in a variety of settings
      and target a large range of health issues. OBJECTIVES: The aim was to assess the
      value of a PCHR in an employee health promotion program for improving knowledge,
      beliefs, and behavior around influenza prevention. METHODS: We evaluated a PCHR
      based employee health promotion program using a randomized controlled trial
      design. Employees at Hewlett Packard work sites who reported reliable Internet
      access and email use at least once every 2 days were recruited for participation.
      PCHRs were provided to all participants for survey administration, and tailored,
      targeted health messages on influenza illness and prevention were delivered to
      participants in the intervention group. Participants in the control group
      received messages addressing cardiovascular health and sun protection. The main
      outcome measure was improvement in knowledge, beliefs, and behavior around
      influenza prevention. Secondary outcomes were influenza vaccine rates among
      household members, the impact of cardiovascular health and sun protection
      messages on the control group, and the usability and utility of the PCHR-based
      program for employees. RESULTS: The intervention did not have a statistically
      significant effect on the influenza knowledge elements we assessed but did impact
      certain beliefs surrounding influenza. Participants in the intervention group
      were more likely to believe that the influenza vaccine was effective (OR = 5.6;
      95% CI = 1.7-18.5), that there were actions they could take to prevent the flu
      (OR = 3.2; 95% CI = 1.1-9.2), and that the influenza vaccine was unlikely to
      cause a severe reaction (OR = 4.4; 95% CI = 1.3-15.3). Immunization rates did not
      differ between the intervention and control groups. However, participants in the
      intervention group were more likely to stay home during an infectious respiratory
      illness compared with participants in the control group (39% [16/41] vs 14%
      [5/35], respectively; P = .02). The program also succeeded in improving
      recognition of the signs of heart attack and stroke among participants in the
      control group. Overall, 78% of participants rated the PCHR as "extremely/very"
      easy to use, and 73% responded that they would be "extremely/very" likely to
      participate again in a PCHR-based health promotion system such as this one.
      CONCLUSIONS: With a small sample size, this study identified a modest impact of a
      PCHR-based employee health program on influenza prevention and control. Employees
      found the PCHR acceptable and easy to use, suggesting that it should be explored
      as a common medium for health promotion in the workplace. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00142077.

PMID- 18343795
TI  - Real-time three-dimensional transoesophageal echocardiography for guidance of
      atrial septal defect closures.

PMID- 18343796
TI  - Thrombus in left ventricular aneurysm: a change in morphology during
      echocardiographic follow-up.

PMID- 18343797
TI  - Severe aortic stenosis with low gradient and apparently preserved left
      ventricular systolic function--under-recognized or overdiagnosed?

PMID- 18343798
TI  - Is dual-source CT coronary angiography ready for the real world?

PMID- 18343799
TI  - Treatment of coronary bifurcations: might less be more?

PMID- 18343800
TI  - Antiviral efficacy, tolerability and pharmacokinetics of efavirenz in an
      unselected cohort of HIV-infected children.
AB  - OBJECTIVES: To obtain data on the pharmacokinetics of efavirenz in children in
      clinical practice. METHODS: HIV-1-infected children received efavirenz capsules
      or tablets in accordance with manufacturer's dosing recommendations. Plasma was
      collected at regular visits and analysed by HPLC. The therapeutic range of
      efavirenz was defined as 1.0-4.0 mg/L. RESULTS: Thirty-three children were
      included. Median (range) age, body weight, dose and dose/kg were 8.2 (2.1-16.7)
      years, 24 (12-62) kg, 300 (200-800) mg and 13.3 (9.7-22.5) mg/kg, respectively.
      Median (range) efavirenz plasma concentration at first sampling was 2.8 (0.13
      11.6) mg/L. Plasma concentrations were not dependent on age (P = 0.97) or dose/kg
      (P = 0.87). A total of 307 efavirenz plasma concentrations were determined. Forty
      five samples (14.7%) contained >4.0 mg/L, and 27 samples (8.8%) contained <1.0
      mg/L. Eight children (24%) reported persistent adverse events probably caused by
      efavirenz [concentration problems (5), sleep disorder (1), psychotic reaction (1)
      and seizure (1)]; six discontinued efavirenz for this reason. A non-significant
      trend existed towards a higher proportion of toxic efavirenz plasma
      concentrations (>4.0 mg/L) in subjects who reported efavirenz adverse events:
      25.9% versus 12.8% (P = 0.23; t-test). Viral load was <50 copies/mL in all 27
      subjects who continued efavirenz, despite occasional subtherapeutic efavirenz
      plasma concentrations in 12 children. The occasional subtherapeutic levels
      suggest that temporal non-adherence was present. CONCLUSIONS: Efavirenz as part
      of highly active antiretroviral therapy was highly effective in children able to
      tolerate the drug. Therapeutic drug monitoring (TDM) as part of toxicity
      management may prevent discontinuation in a subset of patients. Temporal non
      adherence occurs frequently. TDM may allow initiation of adherence interventions
      before viral load becomes detectable.

PMID- 18343801
TI  - Existence of hepatitis C virus NS5B variants naturally resistant to non
      nucleoside, but not to nucleoside, polymerase inhibitors among untreated
      patients.
AB  - OBJECTIVES: To characterize the effect of hepatitis C virus (HCV) polymerase
      intrinsic genetic heterogeneity on the inhibitory activity of nucleoside and non
      nucleoside HCV polymerase inhibitors. METHODS: The sensitivity of genotype (GT) 1
      HCV NS5B clinical isolates from treatment-naive patients to nucleoside and non
      nucleoside polymerase inhibitors was assessed. The genetic diversity at the
      population level, as well as that of their quasispecies, was correlated with the
      observed reduced sensitivity to inhibitors. RESULTS: R1479 and NM107 (nucleoside
      analogues that have entered Phase 2 clinical trials as prodrugs R1626 and NM283,
      respectively) were similarly active across the tested clinical isolates.
      Resistance mutations to nucleoside analogues were not observed in any of the
      isolates. However, the activity of the non-nucleoside thumb II inhibitor NNI-1,
      palm I inhibitors NNI-2 and NNI-3, and palm II inhibitor HCV-796 was reduced
      across different isolates. This reduction in inhibitory activity for non
      nucleoside inhibitors (NNIs) was, in most cases, correlated with the existence of
      known NNI resistance mutations in the NS5B polymerase population of the clinical
      isolates, as detected by population sequencing. Resistance mutations to NNIs were
      also observed at a low frequency within the clinical isolates' viral quasispecies
      that allowed for their rapid selection upon drug selective pressure. CONCLUSIONS:
      The higher frequency of known NNI resistance mutations or polymorphisms known to
      affect their antiviral potency when compared with the lack of detection of
      resistance mutations to the nucleoside analogues suggests a potential for primary
      reduced responsiveness as well as faster development of clinically significant
      resistance.

PMID- 18343802
TI  - Long-term (4 years) efficacy of lopinavir/ritonavir monotherapy for maintenance
      of HIV suppression.
AB  - OBJECTIVES: Data are scarce on the long-term efficacy of lopinavir/ritonavir
      monotherapy for the maintenance of HIV suppression. Four years of results of
      patients randomized to monotherapy in the Only Kaletra (OK) pilot clinical trial
      are presented. PATIENTS AND METHODS: Twenty-one HIV-infected patients with
      suppressed HIV replication (<50 copies/mL) for at least 6 months and without
      previous failure while receiving a protease inhibitor-based regimen started
      lopinavir/ritonavir monotherapy. Follow-up was performed within the OK pilot
      clinical trial during the first 2 years and according to routine clinical
      practice during the 3rd and 4th years. RESULTS: Fourteen patients (67%) remain on
      monotherapy and with RNA <50 copies/mL (intention-to-treat analysis, with missing
      patients scored as failures). Five patients (24%) had virological rebound and all
      of them were successfully re-suppressed by adding two nucleosides. No major
      protease inhibitor mutations were found. CONCLUSIONS: Our data support the long
      term efficacy and safety of lopinavir/ritonavir monotherapy for the maintenance
      of HIV suppression, a finding that must be confirmed in larger studies.

PMID- 18343803
TI  - Polyene susceptibility is dependent on nitrogen source in the opportunistic
      pathogen Candida albicans.
AB  - OBJECTIVES: Polyene antifungal drugs, including amphotericin B or nystatin,
      target ergosterol in the fungal plasma membrane and are used to treat systemic,
      vaginal and oral fungal infections. In the oral cavity, the available nitrogen
      sources are primarily in the form of proteins, which are poor nitrogen sources.
      This study evaluates the effect of protein as a nitrogen source on drug
      susceptibilities. METHODS: Candida albicans was grown in protein [bovine serum
      albumin (BSA) or casein (CSN)] as a sole nitrogen source, in ammonium sulphate
      (AS) as a nitrogen source, or in both protein and AS. RESULTS: Cells grown in BSA
      or CSN were 4- to 16-fold less susceptible to amphotericin B and nystatin than
      those grown in AS. Similar results were observed for cycloheximide, but not for
      fluconazole or caspofungin, and were observed for many C. albicans clinical
      isolates. The results were observed in two different media, and in broth and on
      agar. Cells grown under these nitrogen-poor conditions have a reduction in
      ergosterol sterol levels and a reduction in overall sterol synthesis.
      Quantitative real-time reverse transcription-polymerase chain reaction analysis
      shows that some genes involved in sterol biosynthesis are induced under nitrogen
      limiting conditions, consistent with the lower sterol levels. CONCLUSIONS: The
      results demonstrate that nitrogen source has a significant effect on polyene
      susceptibilities. As these nitrogen-limiting conditions mimic oral nitrogen
      availability, they suggest that in vitro polyene susceptibilities may
      overestimate the in vivo susceptibilities to polyene drugs in the mouth.

PMID- 18343804
TI  - Persistence of PCR-positive tissue in benznidazole-treated mice with negative
      blood parasitological and serological tests in dual infections with Trypanosoma
      cruzi stocks from different genotypes.
AB  - OBJECTIVES: To assess different methodologies to better define an early post
      therapeutic cure criterion after benznidazole treatment in BALB/c mice following
      mixed infection with dual Trypanosoma cruzi genotypes. METHODS: According to the
      classical cure criteria, animals were classified as treated not cured (TNC =
      76.4%), treated cured (TC = 12.5%) and dissociated (DIS = 11.1%) using
      parasitological [fresh blood examination (FBE), blood culture (BC) and blood PCR]
      and serological methods [conventional serology (CS-ELISA) and non-conventional
      serology (NCS-FC-ALTA)]. Tissues were also evaluated by PCR. RESULTS: FBE was
      able to detect patent parasitaemia in only 18.1% of TNC and therapeutic failure
      was detected in 79.1% and 97.2% of TNC by BC and blood PCR, respectively. CS
      ELISA should not be used before 3 months after treatment since it may lead to
      false-negative results. At 3 months after treatment with benznidazole, NCS-FC
      ALTA was more efficient for categorizing the groups of treated mice. In the TNC
      group, although a decreased frequency of PCR-positive tissue was observed in
      several host tissues, increased positivity was also observed, despite the T.
      cruzi genotype combination. All TC animals presented at least two positive tissue
      PCR results. CONCLUSIONS: Our results confirm that NSC-FC-ALTA and blood PCR are
      the most suitable methods to early detect therapeutic failure in acute murine T.
      cruzi infection. Additionally, our data show that BC positivity is highly
      dependent upon the T. cruzi genotype combination. Moreover, our findings
      demonstrated that PCR tests performed on tissues from animals considered cured
      after benznidazole treatment still detected T. cruzi DNA, most probably
      indicating residual infection.

PMID- 18343805
TI  - Qnr-like pentapeptide repeat proteins in gram-positive bacteria.
AB  - OBJECTIVES: To study the role of Qnr-like pentapeptide repeat proteins (PRPs)
      from several gram-positive species with quinolone resistance in vitro. METHODS: A
      PCR-based strategy was used to clone and express genes coding for Qnr-like PRPs
      in Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes,
      Clostridium perfringens, C. difficile, Bacillus cereus and B. subtilis in
      Escherichia coli DH10B. MIC values of nalidixic acid and fluoroquinolones were
      determined for reference strains and E. coli DH10B harbouring recombinant
      plasmids containing genes coding for PRPs. RESULTS: Amino acid identity of Qnr
      like PRPs in gram-positive strains compared with that of the plasmid-mediated
      quinolone resistance determinants QnrA1, QnrB1 and QnrS1 was in the range of 16%
      to 22%. Recombinant plasmids coding for Qnr-like PRPs conferred reduced
      susceptibility to fluoroquinolones (in the range of 0.016 to 0.064 mg/L for
      ciprofloxacin) and nalidixic acid (from 6 to 12 mg/L), depending on the
      antimicrobial agent and PRP. The PRP from B. subtilis showed no protective
      effect. CONCLUSIONS: The PRPs analysed conferred a reduced susceptibility
      phenotype in E. coli; the data provide further evidence of the possible roles in
      quinolone resistance of PRPs from different gram-positive species. These gram
      positive species may constitute a reservoir for Qnr-like quinolone resistance
      proteins.

PMID- 18343806
TI  - Absence of HIV-1 shedding in male genital tract after 1 year of first-line
      lopinavir/ritonavir alone or in combination with zidovudine/lamivudine.
AB  - BACKGROUND: New strategies such as boosted-protease inhibitor (PI) monotherapy
      are being investigated. However, a concern remains regarding the efficacy of this
      strategy in viral sanctuaries such as the male genital tract. More than 80% of
      untreated HIV-infected men have detectable HIV-RNA in semen and such a strategy
      could favour local selection of resistant variants, given the poor penetration of
      most PIs in semen. OBJECTIVES: To evaluate the impact of a first-line
      lopinavir/ritonavir alone or standard triple combination on HIV-1 shedding in the
      genital tract. METHODS: HIV-1-infected men enrolled in the Monark randomized
      trial were eligible for the present study after 48 weeks of a first-line
      lopinavir/ritonavir alone or in combination with zidovudine and lamivudine.
      Single-paired samples of blood and semen were collected at week 48. Blood plasma
      HIV-RNA and seminal plasma HIV-RNA were measured at week 48. Lopinavir and
      ritonavir concentrations were measured in blood and in semen at week 48 by high
      performance liquid chromatography. RESULTS: Ten patients were included: five of
      them received lopinavir/ritonavir monotherapy and five received a triple
      combination. At week 48, all patients had blood plasma HIV-RNA <1.7 log(10)
      copies/mL. Median lopinavir and ritonavir concentrations were within the expected
      therapeutic target range in blood plasma (4896 and 130.5 ng/mL, respectively),
      whereas both lopinavir and ritonavir were undetectable in all seminal plasma
      samples (<30 ng/mL). All 10 patients had undetectable seminal plasma HIV-RNA at
      week 48 (<2.3 log(10) copies/mL). CONCLUSIONS: No local viral production was
      evident in semen, despite the local absence of therapeutic antiretroviral drug
      concentrations in the five patients receiving lopinavir/ritonavir alone.

PMID- 18343807
TI  - Cloning and identification of a novel sperm binding protein, HEL-75, with
      antibacterial activity and expressed in the human epididymis.
AB  - BACKGROUND: The HEL-75 protein is a beta-defensin that was identified by
      analyzing a human epididymis cDNA library. Studying its function may not only
      elucidate the mechanisms of host defense, but may also provide new alternatives
      for novel therapeutic drugs for reproductive tract infections. METHODS: The HEL
      75 gene was amplified by PCR, and its structure and function were predicted and
      analyzed with bioinformatics tools. Polyclonal serum was raised against
      recombinant HEL (rHEL)-75 protein. The gene expression pattern was analyzed with
      RT-PCR and immunofluorescent staining. Finally, the antimicrobial activity and
      function during fertilization of HEL-75 were analyzed using a colony-forming unit
      assay and IVF, respectively. RESULTS: The human HEL-75 gene is located on
      chromosome 20p13 and encodes a 95 amino acid protein with a predicted N-terminal
      signal peptide of 22 amino acids. The protein has six conserved cysteine
      residues, characteristic of members of the beta-defensin superfamily, as well as
      several potential post-translational modification sites. At the transcriptional
      level, HEL-75 was expressed in the epididymis and lung, but only in the
      epididymis at the translational level. Immunofluorescent staining showed that HEL
      75 protein bound spermatozoa in the epididymis. RHEL-75 protein could kill
      Escherichia coli in vitro in a dose- and time-dependent fashion. However, no
      effect was observed on sperm motility nor fertilization when spermatozoa were
      blocked with anti-rHEL-75 polyclonal serum. CONCLUSION: HEL-75 is a new beta
      defensin expressed in the epididymis and on sperm; it may play an important role
      in host defense.

PMID- 18343808
TI  - Retinoids regulate genes involved in retinoic acid synthesis and transport in
      human myometrial and fibroid smooth muscle cells.
AB  - BACKGROUND: Despite the fact that uterine fibroids are the most common benign
      tumors in women, their etiology is poorly understood. We have previously shown
      that multiple members of the retinoic acid (RA) pathway have altered expression
      in fibroids compared with normal myometrium. The aims of the present study were:
      to investigate regulation of genes involved in the RA pathway in vitro; and to
      identify genes that can be used as markers to distinguish myometrial and fibroid
      smooth muscle cells in culture. METHODS AND RESULTS: We demonstrate here for the
      first time that differential expression of aldehyde dehydrogenase 1 (ALDH1)
      between fibroids and myometrium is maintained in cell culture (without
      endothelial cells), and that this gene is differentially regulated by retinoids
      in myometrial compared with fibroid cells. RA and retinol also regulate
      expression of ADH1, cellular retinol binding protein 1 and cellular RA binding
      protein 2 in fibroid and myometrial cells. We show that many of the RA pathway
      genes tested maintain expression levels and differences in vitro. We also
      identify nine genes that are differentially expressed between myometrium and
      fibroids and maintain these differences and expression levels in cultured cells
      isolated from the same tissues. These genes can be used as markers to distinguish
      myometrial and fibroid cells in culture. CONCLUSIONS: Based on these findings, we
      propose that the RA pathway has an important and possible causative role in
      fibroid growth, as evidenced by the large number of genes with significantly
      altered expression in uterine fibroids that can be regulated by RA.

PMID- 18343809
TI  - Seminal anti-Mullerian hormone level is a marker of spermatogenic response during
      long-term gonadotropin therapy in male hypogonadotropic hypogonadism.
AB  - BACKGROUND: In adult men, anti-Mullerian hormone (AMH) levels are higher in semen
      than in serum, but the significance and control of its seminal secretion are
      still unknown. This study evaluated seminal and serum AMH levels during long-term
      gonadotropin therapy in men with hypogonadotropic hypogonadism (HH). METHODS: A
      total of 20 men with never treated prepubertal-onset HH received i.m. hCG to
      normalize testosterone (T) and induce puberty. Afterwards, 11 of them, requiring
      fertility, were treated with HCG plus recombinant FSH (rFSH) (75 IU) twice a
      week, whereas 9 continued to receive hCG alone for 12 months. Before and during
      therapy, serum AMH, inhibin B and T levels were assessed. Semen samples were also
      collected during therapy for sperm count and seminal AMH assay. RESULTS: HCG
      alone decreased basal high serum AMH and stimulated T and inhibin B levels. rFSH
      plus hCG increased seminal AMH levels, which were consequently significantly
      higher than with hCG alone, and positively correlated to sperm densities and
      testicular volumes at 3 and 12 months (P < 0.001). CONCLUSIONS: Our data
      demonstrate that rFSH, added to hCG, stimulates seminal AMH and spermatogenesis
      in HH. Thus, seminal AMH levels are under T and FSH control and are closely
      related to progression of spermatogenesis. Our results also suggest that an early
      seminal AMH increase may be a marker of good future response to gonadotropin
      therapy in HH.

PMID- 18343810
TI  - Ultrasound-guided hydrosalpinx aspiration during oocyte collection improves
      pregnancy outcome in IVF: a randomized controlled trial.
AB  - BACKGROUND: Hydrosalpinges have adverse effects on IVF outcomes. Salpingectomy is
      effective in improving outcomes, but it is not always practical or safe.
      Ultrasound-guided aspiration of hydrosalpinges at oocyte collection is an option
      for those who develop hydrosalpinges during controlled ovarian stimulation;
      however, there is no randomized evidence to show whether this practice is
      effective. METHODS: Between October 1999 and June 2003, consenting women of age
      <or=39 years with an ultrasound diagnosis of hydrosalpinx were randomized before
      oocyte collection to transvaginal aspiration of hydrosalpinx under antibiotics
      cover or no aspiration. Third-party randomization was performed using a computer
      algorithm, and allocation concealment was achieved with opaque sealed envelopes.
      Outcomes were biochemical and clinical pregnancies, implantation, spontaneous
      abortion, ectopic pregnancy and pelvic infection rates. Analysis was by intention
      to treat. RESULTS: Sixty-six women were recruited to the trial, 32 to the
      aspiration group and 34 to the no-aspiration group. Aspiration resulted in a
      greater biochemical pregnancy rate [14/32 (43.8%) versus 7/34 (20.6%), relative
      risk (RR) = 2.1 (1.02, 4.6), P = 0.04]. Clinical pregnancy rates for aspiration
      versus control groups were 31.3% (10/32) and 17.6% (6/34), respectively [RR = 1.8
      (0.8, 4.3), P = 0.20]. There were no changes in implantation rate or spontaneous
      abortion risk with aspiration and no differences between the groups in infection
      or ectopic pregnancy rates. CONCLUSIONS: In women who are identified to have
      hydrosalpinges during controlled ovarian stimulation during IVF, aspiration of
      hydrosalpinges during oocyte collection may be effective in improving pregnancy
      rates (Trial Registration Number: NCT00566956).

PMID- 18343811
TI  - Proteasomes cleave at multiple sites within polyglutamine tracts: activation by
      PA28gamma(K188E).
AB  - Eukaryotic proteasomes have been reported to cleave only once within
      polyglutamine tracts and then only after the N-terminal glutamine (Venkatraman,
      P., Wetzel, R., Tanaka, M., Nukina, N., and Goldberg, A. L. (2004) Mol. Cell 14,
      95-104). We have obtained results that directly conflict with that report. In the
      presence of the proteasome activator PA28gamma(K188E) human red cell proteasomes
      progressively degraded fluorescein-GGQ(10)RR or fluorescein-HPHQ(10)RR into small
      fragments as shown by size exclusion chromatography and mass spectrometry. MALDI
      TOF mass spectrometry revealed that proteolytic products arose from cleavage
      after every glutamine in fluorescein-HPHQ(10)RR, and mass accuracy rules out
      deamidation of glutamine to glutamic acid as an explanation for peptide
      degradation. Moreover, degradation cannot be attributed to a contaminating
      protease because peptide hydrolysis was completely blocked by the proteasome
      specific inhibitors, lactacystin and epoxomicin. We conclude that proteasomes
      cleave repetitively anywhere within a stretch of ten glutamine residues. Thus our
      results cast doubt on the idea that mammalian proteasomes cannot degrade
      glutamine-expanded regions within pathogenic polyQ-expanded proteins, such as
      Huntingtin.

PMID- 18343812
TI  - A PY-NLS nuclear targeting signal is required for nuclear localization and
      function of the Saccharomyces cerevisiae mRNA-binding protein Hrp1.
AB  - Proteins destined for import into the nucleus contain nuclear localization
      signals (NLSs) that are recognized by import receptors termed karyopherins or
      importins. Until recently, the only nuclear import sequence that had been well
      defined and characterized was the classical NLS (cNLS), which is recognized by
      importin alpha. However, Chook and coworkers (Lee, B. J., Cansizoglu, A. E.,
      Suel, K. E., Louis, T. H., Zhang, Z., and Chook, Y. M. (2006) Cell 126, 543-558)
      have provided new insight into nuclear targeting with their identification of a
      novel NLS, termed the PY-NLS, that is recognized by the human karyopherin
      beta2/transportin (Kapbeta2) receptor. Here, we demonstrate that the PY-NLS is
      conserved in Saccharomyces cerevisiae and show for the first time that the PY-NLS
      is a functional nuclear targeting sequence in vivo. The apparent ortholog of
      Kapbeta2 in yeast, Kap104, has two known cargos, the mRNA-binding proteins Hrp1
      and Nab2, which both contain putative PY-NLS-like sequences. We find that the PY
      NLS-like sequence within Hrp1, which closely matches the PY-NLS consensus, is
      both necessary and sufficient for nuclear import and is also required for
      receptor binding and protein function. In contrast, the PY-NLS-like sequences in
      Nab2, which vary from the PY-NLS consensus, are not required for proper import or
      protein function, suggesting that Kap104 may interact with different cargos using
      multiple mechanisms. Dissection of the PY-NLS consensus reveals that the minimal
      PY-NLS in yeast consists of the C-terminal portion of the human consensus,
      R/H/KX(2-5)PY, with upstream basic or hydrophobic residues enhancing the
      targeting function. Finally, we apply this analysis to a bioinformatic search of
      the yeast proteome as a preliminary search for new potential Kap104 cargos.

PMID- 18343813
TI  - Scrambled isomers as key intermediates in the oxidative folding of ligand binding
      module 5 of the low density lipoprotein receptor.
AB  - The ligand binding module five (LA5) of the low density lipoprotein receptor is a
      small, single-domain protein of 40 residues and three disulfide bonds with a
      calcium binding motif that is essential for its structure and function. Several
      mutations in LA5 have been reported to cause familial hypercholesterolemia by
      impairing a proper folding of the module. The current study reports the oxidative
      folding and reductive unfolding pathways of wild type and mutant LA5 modules
      through kinetic and structural analysis of the trapped intermediates. Wild type
      LA5 folding involves an initial phase of nonspecific packing where the sequential
      oxidation of its cysteines gives rise to complex equilibrated populations of
      intermediates. In the presence of calcium, the attainment of a coordination
      competent conformation becomes the rate-limiting step of folding while binding of
      the ion funnels both thermodynamically and kinetically the folding reaction
      toward the native state. In the absence of calcium, a scrambled isomer (termed
      Xa) constitutes the global free energy minimum of the folding process. Xa and the
      native form are stable, inter-convertible species whose relative populations at
      equilibrium appear displaced in disease-linked mutants toward the scrambled form.
      Because stable scrambled isomers such as Xa avoid the exposition of reactive
      cysteines in misfolded modules, they might constitute a strategy to prevent wrong
      interactions with other domains during folding of the receptor. Comparison of the
      folding pathways of wild type and mutant LA5 provides the molecular basis to
      understand how LA modules fold into a functional conformation or upon mutation
      misfold and lead to disease.

PMID- 18343814
TI  - Phosphorylation at Ser-129 but not the phosphomimics S129E/D inhibits the
      fibrillation of alpha-synuclein.
AB  - alpha-Synuclein (alpha-syn) phosphorylation at serine 129 is characteristic of
      Parkinson disease (PD) and related alpha-synulceinopathies. However, whether
      phosphorylation promotes or inhibits alpha-syn aggregation and neurotoxicity in
      vivo remains unknown. This understanding is critical for elucidating the role of
      alpha-syn in the pathogenesis of PD and for development of therapeutic strategies
      for PD. To better understand the structural and molecular consequences of Ser-129
      phosphorylation, we compared the biochemical, structural, and membrane binding
      properties of wild type alpha-syn to those of the phosphorylation mimics (S129E,
      S129D) as well as of in vitro phosphorylated alpha-syn using a battery of
      biophysical techniques. Our results demonstrate that phosphorylation at Ser-129
      increases the conformational flexibility of alpha-syn and inhibits its
      fibrillogenesis in vitro but does not perturb its membrane-bound conformation. In
      addition, we show that the phosphorylation mimics (S129E/D) do not reproduce the
      effect of phosphorylation on the structural and aggregation properties of alpha
      syn in vitro. Our findings have significant implications for current strategies
      to elucidate the role of phosphorylation in modulating protein structure and
      function in health and disease and provide novel insight into the underlying
      mechanisms that govern alpha-syn aggregation and toxicity in PD and related alpha
      synulceinopathies.

PMID- 18343815
TI  - Defining the importance of phosphatidylserine synthase-1 (PSS1): unexpected
      viability of PSS1-deficient mice.
AB  - Phosphatidylserine (PS) is a quantitatively minor, but physiologically important,
      phospholipid in mammalian cells. PS is synthesized by two distinct base-exchange
      enzymes, PS synthase-1 (PSS1) and PS synthase-2 (PSS2), that are encoded by
      different genes. PSS1 exchanges serine for choline of phosphatidylcholine,
      whereas PSS2 exchanges ethanolamine of phosphatidylethanolamine for serine. We
      previously generated mice lacking PSS2 (Bergo, M. O., Gavino, B. J., Steenbergen,
      R., Sturbois, B., Parlow, A. F., Sanan, D. A., Skarnes, W. C., Vance, J. E., and
      Young, S. G. (2002) J. Biol. Chem. 277, 47701-47708) and found that PSS2 is not
      required for mouse viability. We have now generated PSS1-deficient mice. In light
      of the markedly impaired survival of Chinese hamster ovary cells lacking PSS1 we
      were surprised that PSS1-deficient mice were viable, fertile, and had a normal
      life span. Total serine-exchange activity (contributed by PSS1 and PSS2) in
      tissues of Pss1(-/-) mice was reduced by up to 85%, but except in liver, the PS
      content was unaltered. Despite the presumed importance of PS in the nervous
      system, the rate of axonal extension of PSS1-deficient neurons was normal.
      Intercrosses of Pss1(-/-) mice and Pss2(-/-) mice yielded mice with three
      disrupted Pss alleles but no double knockout mice. In Pss1(-/-)/Pss2(-/-) and
      Pss1(-/-)/Pss2(-/-) mice, serine-exchange activity was reduced by 65-91%, and the
      tissue content of PS and phosphatidylethanolamine was also decreased. We conclude
      that (i) elimination of either PSS1 or PSS2, but not both, is compatible with
      mouse viability, (ii) mice can tolerate as little as 10% of normal total serine
      exchange activity, and (iii) mice survive with significantly reduced PS and
      phosphatidylethanolamine content.

PMID- 18343816
TI  - Cytochrome bc1-cy fusion complexes reveal the distance constraints for functional
      electron transfer between photosynthesis components.
AB  - Photosynthetic (Ps) growth of purple non-sulfur bacteria such as Rhodobacter
      capsulatus depends on the cyclic electron transfer (ET) between the
      ubihydroquinone (QH2): cytochrome (cyt) c oxidoreductases (cyt bc1 complex), and
      the photochemical reaction centers (RC), mediated by either a membrane-bound (cyt
      c(y)) or a freely diffusible (cyt c2) electron carrier. Previously, we
      constructed a functional cyt bc1-c(y) fusion complex that supported Ps growth
      solely relying on membrane-confined ET ( Lee, D.-W., Ozturk, Y., Mamedova, A.,
      Osyczka, A., Cooley, J. W., and Daldal, F. (2006) Biochim. Biophys. Acta 1757,
      346-352 ). In this work, we further characterized this cyt bc1-c(y) fusion
      complex, and used its derivatives with shorter cyt c(y) linkers as "molecular
      rulers" to probe the distances separating the Ps components. Comparison of the
      physicochemical properties of both membrane-embedded and purified cyt bc1-c(y)
      fusion complexes established that these enzymes were matured and assembled
      properly. Light-activated, time-resolved kinetic spectroscopy analyses revealed
      that their variants with shorter cyt c(y) linkers exhibited fast, native-like ET
      rates to the RC via the cyt bc1. However, shortening the length of the cyt c(y)
      linker decreased drastically this electronic coupling between the cyt bc1-c(y)
      fusion complexes and the RC, thereby limiting Ps growth. The shortest and still
      functional cyt c(y) linker was about 45 amino acids long, showing that the
      minimal distance allowed between the cyt bc1-c(y) fusion complexes and the RC and
      their surrounding light harvesting proteins was very short. These findings
      support the notion that membrane-bound Ps components form large, active
      structural complexes that are "hardwired" for cyclic ET.

PMID- 18343817
TI  - Soluble variants of Rhodobacter capsulatus membrane-anchored cytochrome cy are
      efficient photosynthetic electron carriers.
AB  - Photosynthetic (Ps) electron transport pathways often contain multiple electron
      carriers with overlapping functions. Here we focus on two c-type cytochromes
      (cyt) in facultative phototrophic bacteria of the Rhodobacter genus: the
      diffusible cyt c2 and the membrane-anchored cyt c(y). In species like R.
      capsulatus, cyt c(y) functions in both Ps and respiratory electron transport
      chains, whereas in other species like R. sphaeroides, it does so only in
      respiration. The molecular bases of this difference was investigated by producing
      a soluble variant of cyt c(y) (S-c(y)), by fusing genetically the cyt c2 signal
      sequence to the cyt c domain of cyt c(y). This novel electron carrier was unable
      to support the Ps growth of R. capsulatus. However, strains harboring cyt S-c(y)
      regained Ps growth ability by acquiring mutations in its cyt c domain. They
      produced cyt S-c(y) variants at amounts comparable with that of cyt c2, and
      conferred Ps growth. Chemical titration indicated that the redox midpoint
      potential of cyt S-c(y) was about 340 mV, similar to that of cyts c2 or c(y).
      Remarkably, electron transfer kinetics from the cyt bc1 complex to the
      photochemical reaction center (RC) mediated by cyt S-c(y) was distinct from those
      seen with the cyt c2 or cyt c(y). The kinetics exhibited a pronounced slow phase,
      suggesting that cyt S-c(y) interacted with the RC less tightly than cyt c2.
      Comparison of structural models of cyts c2 and S-c(y) revealed that several of
      the amino acid residues implicated in long-range electrostatic interactions
      promoting binding of cyt c2 to the RC are not conserved in cyt c(y), whereas
      those supporting short-range hydrophobic interactions are conserved. These
      findings indicated that attaching electron carrier cytochromes to the membrane
      allowed them to weaken their interactions with their partners so that they could
      accommodate more rapid multiple turnovers.

PMID- 18343818
TI  - Transforming growth factor-beta-stimulated endocardial cell transformation is
      dependent on Par6c regulation of RhoA.
AB  - Valvular heart disease due to congenital abnormalities or pathology is a major
      cause of mortality and morbidity. Understanding the cellular processes and
      molecules that regulate valve formation and remodeling is required to develop
      effective therapies. In the developing heart, epithelial-mesenchymal
      transformation (EMT) in a subpopulation of endocardial cells in the
      atrioventricular cushion (AVC) is an important step in valve formation.
      Transforming growth factor-beta (TGFbeta) has been shown to be an important
      regulator of AVC endocardial cell EMT in vitro and mesenchymal cell
      differentiation in vivo. Recently Par6c (Par6) has been shown to function
      downstream of TGFbeta to recruit Smurf1, an E3 ubiquitin ligase, which targets
      RhoA for degradation to control apical-basal polarity and tight junction
      dissolution. We tested the hypothesis that Par6 functions in a pathway that
      regulates endocardial cell EMT. Here we show that the Type I TGFbeta receptor
      ALK5 is required for endocardial cell EMT. Overexpression of dominant negative
      Par6 inhibits EMT in AVC endocardial cells, whereas overexpression of wild-type
      Par6 in normally non-transforming ventricular endocardial cells results in EMT.
      Overexpression of Smurf1 in ventricular endocardial cells induces EMT. Decreasing
      RhoA activity using dominant negative RhoA or small interfering RNA in
      ventricular endocardial cells also increases EMT, whereas overexpression of
      constitutively active RhoA in AVC endothelial cells blocks EMT. Manipulation of
      Rac1 or Cdc42 activity is without effect. These data demonstrate a functional
      role for Par6/Smurf1/RhoA in regulating EMT in endocardial cells.

PMID- 18343819
TI  - PGC-1-related coactivator complexes with HCF-1 and NRF-2beta in mediating NRF
      2(GABP)-dependent respiratory gene expression.
AB  - The PGC-1 family of regulated coactivators (PGC-1alpha, PGC-1beta, and PRC) plays
      an important role in directing respiratory gene expression in response to
      environmental signals. Here, we show that PRC and PGC-1alpha differ in their
      interactions with nuclear hormone receptors but are highly similar in their
      direct binding to several nuclear transcription factors implicated in the
      expression of the respiratory chain. Surprisingly, neither coactivator binds NRF
      2(GABP), a multisubunit transcriptional activator associated with the expression
      of many respiratory genes. However, the NRF-2 subunits and PRC are co
      immunoprecipitated from cell extracts indicating that the two proteins exist in a
      complex in vivo. Several lines of evidence indicate that HCF-1 (host cell factor
      1), a major chromatin component, mediates the association between PRC and NRF-2.
      Both PRC and NRF-2beta bind HCF-1 in vitro, and the molecular determinants
      required for the interactions of each with HCF-1 are also required for PRC trans
      activation through promoter-bound NRF-2. These determinants include a consensus
      HCF-1 binding site on PRC and the NRF-2 activation domain. In addition, PRC and
      NRF-2beta can complex with HCF-1 in vivo, and all three associate with NRF-2
      dependent nuclear genes that direct the expression of the mitochondrial
      transcription factors, TFB1M and TFB2M. Finally, short hairpin RNA-mediated knock
      down of PRC protein levels leads to reduced expression of TFB2M mRNA and
      mitochondrial transcripts for cytochrome oxidase II (COXII) and cytochrome b.
      These changes in gene expression coincide with a marked reduction in cytochrome
      oxidase activity. The results are consistent with a pathway whereby PRC regulates
      NRF-2-dependent genes through a multiprotein complex involving HCF-1.

PMID- 18343820
TI  - Glial cell line-derived neurotrophic factor reverses ethanol-mediated increases
      in tyrosine hydroxylase immunoreactivity via altering the activity of heat shock
      protein 90.
AB  - We previously found that glial cell line-derived neurotrophic factor (GDNF) in
      the midbrain ventral tegmental area (VTA) negatively regulates alcohol drinking
      (He, D. Y., McGough, N. N., Ravindranathan, A., Jeanblanc, J., Logrip, M. L.,
      Phamluong, K., Janak, P. H., and Ron, D. (2005) J. Neurosci. 25, 619-628).
      Several studies suggest a role for GDNF in the regulation of tyrosine hydroxylase
      (TH) levels in the midbrain (Georgievska, B., Kirik, D., and Bjorklund, A. (2004)
      J. Neurosci. 24, 6437-6445). Up-regulation of TH levels has been reported as a
      hallmark of biochemical adaptations to in vivo chronic exposure to drugs of
      abuse, including ethanol (Ortiz, J., Fitzgerald, L. W., Charlton, M., Lane, S.,
      Trevisan, L., Guitart, X., Shoemaker, W., Duman, R. S., and Nestler, E. J. (1995)
      Synapse 21, 289-298). We hypothesized that GDNF plays an important role in
      regulating prolonged ethanol-mediated increases in TH protein levels. Using the
      SH-SY5Y dopaminergic-like cell line, we found that the increase in TH levels in
      the presence of ethanol required the activation of the cAMP/PKA pathway and was
      reversed by GDNF. Ethanol treatment did not alter the mRNA level or protein
      translation of TH, but enhanced the stability of the protein that was decreased
      by GDNF. Interestingly, we observed that ethanol treatment resulted in an
      increase in TH association with the chaperone heat shock protein (HSP90) that was
      mediated by the cAMP/PKA pathway and inhibited by GDNF. Taken together, these
      data suggest that prolonged ethanol exposure leads to increased association of TH
      and HSP90 via the cAMP/PKA pathway, resulting in the stabilization and subsequent
      accumulation of TH. GDNF reverses this ethanol-mediated adaptation by inhibiting
      the interaction of TH with HSP90.

PMID- 18343821
TI  - Determination of three-dimensional structure and residues of the novel tumor
      suppressor AIMP3/p18 required for the interaction with ATM.
AB  - Although AIMP3/p18 is normally associated with the multi-tRNA synthetase complex
      via its specific interaction with methionyl-tRNA synthetase, it also works as a
      tumor suppressor by interacting with ATM, the upstream kinase of p53. To
      understand the molecular interactions of AIMP3 and the mechanisms involved, we
      determined the crystal structure of AIMP3 at 2.0-angstroms resolution and
      identified its potential sites of interaction with ATM. AIMP3 contains two
      distinct domains linked by a 7-amino acid (Lys57-Ser63) peptide, which contains a
      3(10) helix. The 56-amino acid N-terminal domain consists of two helices into
      which three antiparallel beta strands are inserted, and the 111-amino acid C
      terminal domain contains a bundle of five helices (Thr64-Tyr152) followed by a
      coiled region (Pro153-Leu169). Structural analyses revealed homologous proteins
      such as yeast glutamyl-tRNA synthetase, Arc1p, EF1Bgamma, and glutathione S
      transferase and suggested two potential molecular binding sites. Moreover,
      mutations at the C-terminal putative binding site abolished the interaction
      between AIMP3 and ATM and the ability of AIMP3 to activate p53. Thus, this work
      identified the two potential molecular interaction sites of AIMP3 and determined
      the residues critical for its tumor-suppressive activity through the interaction
      with ATM.

PMID- 18343822
TI  - The origins of enhanced activity in factor VIIa analogs and the interplay between
      key allosteric sites revealed by hydrogen exchange mass spectrometry.
AB  - Factor VIIa (FVIIa) circulates in the blood in a zymogen-like state. Only upon
      association with membrane-bound tissue factor (TF) at the site of vascular injury
      does FVIIa become active and able to initiate blood coagulation. Here we used
      hydrogen exchange monitored by mass spectrometry to investigate the
      conformational effects of site-directed mutagenesis at key positions in FVIIa and
      the origins of enhanced intrinsic activity of FVIIa analogs. The differences in
      hydrogen exchange of two highly active variants, FVIIa(DVQ) and FVIIa(VEAY),
      imply that enhanced catalytic efficiency was attained by two different
      mechanisms. Regions protected from exchange in FVIIa(DVQ) include the N-terminal
      tail and the activation pocket, which is a subset of the regions of FVIIa
      protected from exchange upon TF binding. FVIIa(DVQ) appeared to adopt an
      intermediate conformation between the free (zymogen-like) and TF-bound (active)
      form of FVIIa and to attain enhanced activity by partial mimicry of TF-induced
      activation. In contrast, exchange-protected regions in FVIIa(VEAY) were confined
      to the vicinity of the active site of FVIIa. Thus, the changes in FVIIa(VEAY)
      appeared to optimize the active site region rather than imitate the TF-induced
      effect. Hydrogen exchange analysis of the FVIIa(M306D) variant, which was
      unresponsive to stimulation by TF, correlated widespread reductions in exchange
      to the single mutation in the TF-binding region. These results reveal the
      delicate interplay between key allosteric sites necessary to achieve the
      transition of FVIIa into the active form.

PMID- 18343823
TI  - Causes, prognostic factors and treatment results of acute renal failure in
      children treated in a tertiary hospital in South Africa.
AB  - The aim of this study was to determine the causes, prognostic factors and
      treatment results of acute renal failure (ARF) in children admitted to the
      Pretoria Academic Hospital from 1986 to 2002. A retrospective chart review of 102
      children (mean age 37 months) was done. Various factors were analysed including
      age, sex, causes of ARF, morbidity, mortality, dialysis requirement and outcome.
      Peritoneal dialysis was the only form of dialysis available. Patients were
      categorized as those who survived without dialysis or in whom renal function
      recovered without the need for continuing dialysis (Group I, termed 'survivors'),
      and those who died or remained dialysis dependent (Group II, termed 'non
      survivors'). The most common causes of ARF were haemolytic uraemic syndrome
      (35.3%), acute tubular necrosis (31.4%) and acute glomerulonephritis (15.7%).
      There were 77 patients in Group I of whom 38 required dialysis, and 25 in Group
      II of whom 16 were dialysed. Fifteen patients in Group II died and 10 remained
      dialysis dependent ('renal deaths'). Only four patients with 'renal death'
      received long-term dialysis. Coma (P < 0.001), liver dysfunction (P < 0.009), a
      clotting deficiency (P < 0.001), respiratory failure (P < 0.001) and multi-organ
      failure (P < 0.001) were significantly associated with poor outcome. These
      factors should be taken into account before initiating dialysis in children in
      countries where available resources for long-term dialysis are limited.

PMID- 18343824
TI  - Diversity of the a sequence of herpes simplex virus type 1 developed during
      evolution.
AB  - Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen. The a
      sequence of HSV-1 is the cis-acting site required for the cleavage and
      encapsidation of unit-length HSV-1 DNA from concatemeric forms. The consensus a
      sequence consists of (i) DR1 (direct repeat 1), (ii) Ub, (iii) a DR2 array [a
      repeat of various copy numbers of DR2 elements (11 or 12 bp)], (iv) a DR4 stretch
      and (v) Uc. In the present study, the nucleotide sequences of the a sequences of
      26 HSV-1 isolates were determined and the DR4 stretches were classified into
      three groups. The state of a set of 20 DNA polymorphisms in the genomes of these
      HSV-1 isolates was determined previously. A correct classification rate of 100 %
      was achieved when discriminant analysis was performed between the DR4 stretch
      (criterion variable) and the set of 20 DNA polymorphisms (predictor variables),
      suggesting a close association of the DR4 stretch with HSV-1 diversification. DR2
      elements of 9, 13 and 14 bp were detected in addition to those of 11 and 12 bp,
      and a correct classification rate of 93 % was achieved when discriminant analysis
      was performed between the DR2 array and the set of 20 DNA polymorphisms. Some DR2
      elements of one HSV-1 isolate had the same nucleotide sequences as part of the
      adjacent DR4 stretch, and these variations were adequately explained by
      postulating recombination involving DR2 elements; hence, the DR2 array was
      deduced to be prone to recombination.

PMID- 18343825
TI  - Human cytomegalovirus serum neutralizing antibodies block virus infection of
      endothelial/epithelial cells, but not fibroblasts, early during primary
      infection.
AB  - A panel of human sera exhibited a >or=128-fold higher neutralizing potency
      against a human cytomegalovirus (HCMV) clinical isolate propagated and tested in
      endothelial (or epithelial) cells than against the same virus infecting human
      fibroblasts. In a group of 18 primary infections, the reverse geometric mean
      titre was in the range of 10-15 in human fibroblasts within the first 3 months
      after the onset of infection, whereas the endothelial cell infection-neutralizing
      activity was already present within the first 10 days, reaching median levels of
      122, 320 and 545 at respectively 30, 60 and 90 days after onset, then declining
      slowly. This difference was also confirmed in the majority of reactivated and
      remote HCMV infections, as well as in a hyperimmune globulin preparation. The
      antibody response to HCMV pUL131A, pUL130 and pUL128 locus products, which are
      required for endothelial/epithelial cell infection, provided a potential
      molecular basis for such a differential neutralizing activity. In addition,
      monoclonal/monospecific antibodies raised against the pUL131A, pUL130 and pUL128
      proteins were found to display an inhibitory activity on HCMV plaque formation
      and HCMV leukocyte transfer from HCMV-infected cells. Hence, conventional
      determination of the neutralizing activity of human sera in fibroblasts is
      misleading. Antibodies to pUL131A, pUL130 and pUL128 appear to display a major
      HCMV-neutralizing and dissemination-inhibiting activity.

PMID- 18343826
TI  - Epstein-Barr virus nuclear antigen (EBNA) 3A induces the expression of and
      interacts with a subset of chaperones and co-chaperones.
AB  - Viral nuclear oncoproteins EBNA3A and EBNA3C are essential for the efficient
      immortalization of B cells by Epstein-Barr virus (EBV) in vitro and it is assumed
      that they play an essential role in viral persistence in the human host. In order
      to identify cellular genes regulated by EBNA3A expression, cDNA encoding EBNA3A
      was incorporated into a recombinant adenoviral vector. Microarray analysis of
      human diploid fibroblasts infected with either adenovirus EBNA3A or an empty
      control adenovirus consistently showed an EBNA3A-specific induction of mRNA
      corresponding to the chaperones Hsp70 and Hsp70B/B' and co-chaperones Bag3 and
      DNAJA1/Hsp40. Analysis of infected fibroblasts by real-time quantitative RT-PCR
      and Western blotting confirmed that EBNA3A, but not EBNA3C, induced expression of
      Hsp70, Hsp70B/B', Bag3 and DNAJA1/Hsp40. This was also confirmed in a stable,
      inducible expression system. EBNA3A activated transcription from the Hsp70B
      promoter, but not multimerized heat-shock elements in transient transfection
      assays, consistent with specific chaperone and co-chaperone upregulation. Co
      immunoprecipitation experiments suggest that EBNA3A can form a complex with the
      chaperone/co-chaperone proteins in both adenovirus-infected cells and EBV
      immortalized lymphoblastoid cell lines. Consistent with this, induction of EBNA3A
      resulted in redistribution of Hsp70 from the cytoplasm to the nucleus. EBNA3A
      therefore specifically induces (and then interacts with) all of the factors
      necessary for an active Hsp70 chaperone complex.

PMID- 18343827
TI  - Essential role of PKCdelta in histone deacetylase inhibitor-induced Epstein-Barr
      virus reactivation in nasopharyngeal carcinoma cells.
AB  - Histone deactylase inhibitors (HDACi) are common chemotherapeutic agents that
      stimulate Epstein-Barr virus (EBV) reactivation; the detailed mechanism remains
      obscure. In this study, it is demonstrated that PKCdelta is required for
      induction of the EBV lytic cycle by HDACi. Inhibition of PKCdelta abrogates HDACi
      mediated transcriptional activation of the Zta promoter and downstream lytic gene
      expression. Nuclear translocation of PKCdelta is observed following HDACi
      stimulation and its overexpression leads to progression of the EBV lytic cycle.
      Our study suggests that PKCdelta is a crucial mediator of EBV reactivation and
      provides a novel insight to study the regulation of the EBV lytic cycle.

PMID- 18343828
TI  - Effect of phosphorylation on the transactivation activity of Epstein-Barr virus
      BMRF1, a major target of the viral BGLF4 kinase.
AB  - Modification of human herpesvirus DNA polymerase processivity factors (PFs) by
      phosphorylation occurs frequently during viral lytic replication. However,
      functional regulation of the herpesvirus PFs through phosphorylation is not well
      understood. In addition to processivity, the PF BMRF1 of Epstein-Barr virus can
      function as a transactivator to activate the BHLF1 promoter within the lytic
      origin of replication (oriLyt), which is assumed to facilitate DNA replication
      through remodelling viral chromatin structure. BMRF1 is known to be
      phosphorylated by the viral BGLF4 kinase, but its impact on BMRF1 function is
      unclear. Seven candidate BGLF4 target sites were predicted within a proline-rich
      region between the DNA-processivity and nuclear-localization domains of BMRF1. We
      show that four of these residues, Ser-337, Thr-344, Ser-349 and Thr-355, are
      responsible for the BGLF4-induced hyperphosphorylation of BMRF1. In functional
      analyses, a phosphorylation-mimicking mutant of BMRF1 shows similar nuclear
      localization, as well as DNA-binding ability, to the wild type; however, it
      displays stronger synergistic activation of the BHLF1 promoter with Zta. Notably,
      BGLF4 downregulates BMRF1 transactivation and enhances the transactivation
      activity of Zta and the synergistic activation of BMRF1 and Zta on the BHLF1
      promoter. Our findings suggest that BGLF4 may modulate the activation of the
      oriLyt BHLF1 promoter coordinately through multiple mechanisms to facilitate
      optimal oriLyt-dependent viral DNA replication.

PMID- 18343829
TI  - Identification of envelope protein pORF81 of koi herpesvirus.
AB  - Koi herpesvirus (KHV), an emerging pathogen causing mass mortality in koi and
      common carp, possesses the largest known herpesvirus genome of 295 kbp predicted
      to encode 156 different proteins. However, none of them has been identified or
      functionally characterized up to now. In this study, a rabbit antiserum was
      prepared against a bacterial fusion protein that permitted detection of the
      predicted type III membrane protein encoded by ORF81 of KHV. In Western blot
      analyses, the abundant ORF81 gene product of KHV exhibited an apparent mass of 26
      kDa and appeared to be non-glycosylated. It could be localized in the cytoplasm
      of infected cells and in virion envelopes by indirect immunofluorescence and
      immunoelectron microscopy, respectively. The antiserum was also suitable for the
      detection of pORF81 in sections of gills, kidneys, hepatopancreas and skin of KHV
      infected carp by immunohistochemistry.

PMID- 18343830
TI  - Effect of basal core promoter and pre-core mutations on hepatitis B virus
      replication.
AB  - There are two hypotheses explaining a fulminant outcome after hepatitis B virus
      (HBV) infection, both of which may be applicable at the same time: (i) basal core
      promoter (BCP) mutations increase viral replication, allowing rapid spread of the
      virus through the liver, and (ii) pre-core (pre-C) mutations abrogating hepatitis
      B e antigen (HBeAg) synthesis remove its tolerogenic effect, leading to a
      vigorous immune response. This study investigated the effect of these mutations
      on virus replication efficiency and HBeAg production. Substitutions A1762T/G1764A
      and T1753C, C1766T and T1768A in the BCP region, and G1896A and G1899A in the pre
      C region, were examined either alone or in combination, using a common genetic
      background. Huh7 cells were transfected with these constructs and real-time PCR
      was used to quantify released virion-associated and intracellular HBV DNA,
      pregenomic RNA and pre-C mRNA. In addition, culture supernatants were tested for
      hepatitis B surface antigen (HBsAg) and HBeAg. The double BCP mutation
      (A1762T/G1764A) and the pre-C mutations (G1896A, G1899A), either alone or in
      combination, had no appreciable effect on the replication capacity of the virus.
      In contrast, clones with mutations at positions 1766/1768, 1762/1764/1766 and
      1753/1762/1764 exhibited increased-replication phenotypes. HBeAg was undetectable
      in all cultures transfected with constructs bearing the G1896A stop-codon
      mutation, as expected. In contrast, constructs with additional mutations in the
      BCP region had appreciably lower levels of HBeAg expression than the wild type.
      Thus, core promoter mutations other than those at 1762/1764 appear to upregulate
      viral DNA replication and, at the same time, greatly reduce HBeAg production.

PMID- 18343831
TI  - Association of serum and mucosal neutralizing antibodies to human papillomavirus
      type 16 (HPV-16) with HPV-16 infection and cervical disease.
AB  - We investigated neutralizing antibodies to human papillomavirus type 16 (HPV-16)
      in serum and cervical washes from 84 women with normal cytology or cervical
      disease. Serum neutralizing antibodies were detected in 78 % of women infected at
      the cervix with HPV-16, compared with 35 % (P=0.002) of women infected with HPV
      16-related types (alpha9 HPV types), 14 % (P<0.0001) of women infected with HPV
      16 non-related types and none of HPV-uninfected women. A significant correlation
      between HPV-16 infection and serum HPV-16-neutralizing antibodies was observed
      (r(s)=0.97; P=0.032). Cervical neutralizing antibodies were detected in 38 % of
      women with HPV-16 infection and in 17 % of women infected with the HPV-16-related
      type HPV-31. Cervical neutralizing antibodies correlated with HPV-16 infection
      (r(s)=0.95; P=0.08), but not with cervical disease. Serum and cervical HPV-16
      antibody responses were not affected significantly by human immunodeficiency
      virus type 1 infection. In conclusion, serum and cervical HPV-16-neutralizing
      antibodies were found to correlate with HPV-16 infection, but not with cervical
      disease.

PMID- 18343832
TI  - In vivo characterization of two granuloviruses in larvae of Mythimna separata
      (Lepidoptera: Noctuidae).
AB  - The pathogenicity of two granuloviruses (GVs), Xestia c-nigrum GV (XecnGV) and
      Pseudaletia unipuncta GV (PsunGV), was examined in Mythimna separata. Partial
      sequencing of the genome of PsunGV indicated that it is related closely to
      XecnGV, but considered to be a different species. PsunGV and XecnGV showed
      similar pathogenicity in terms of dose-mortality response and pattern of host
      mass changes following infection. Both GVs killed infected larvae in 2-3 weeks.
      Temporal changes in the concentrations of GV-specific DNA in the larval
      haemolymph were measured by using a real-time quantitative PCR. Viral DNA
      concentration increased quickly and reached a plateau at 60-72 h post
      inoculation. Rates of budded virus (BV) production of each GV were estimated on
      the basis of viral DNA concentrations by a modified Gompertz model. The slopes of
      the estimated BV growth curves of both XecnGV and PsunGV in M. separata larvae
      were equivalent to that of Mamestra brassicae nucleopolyhedrovirus (NPV) in its
      original host, reported in our previous study. This suggested that BV production
      is not a major factor in the slower killing speed of GVs in comparison to NPVs.
      The GV-infected larvae survived for an additional 10 days or more after reaching
      a maximum level of BV concentration, and kept growing without pupation. These
      findings also suggested that the GVs have a unique mechanism to regulate the
      growth of host larvae.

PMID- 18343833
TI  - Open reading frame Bm21 of Bombyx mori nucleopolyhedrovirus is not essential for
      virus replication in vitro, but its deletion extends the median survival time of
      infected larvae.
AB  - In this report, the open reading frame 21 (Bm21) of Bombyx mori
      nucleopolyhedrovirus (BmNPV), one of the unique genes of group I NPVs, was
      characterized. Bm21 is predicted to encode a protein of 55.8 kDa and was found to
      contain imperfectly conserved leucine-rich repeats. 3' Rapid amplification of
      cDNA ends (3'RACE) showed that the transcript of Bm21 was first detected from 6 h
      post-infection and that it also encompassed the complete Bm20. 5'RACE revealed
      three transcription initiation sites, one of which mapped to the baculovirus
      early transcription motifs CGTGC and CAGT. Transient-expression and
      superinfection assays indicated that BM21 localized in the nucleus of infected
      BmN cells. To study the function of BM21, a Bm21-null virus was constructed using
      bacmid technology. Viral one-step growth curve analyses showed that the Bm21-null
      virus had similar budded virus production kinetics to those of the parental
      virus. Bioassay analyses showed that the median lethal concentration (LC(50)) of
      the Bm21-null virus was similar to that of the control virus; however, the median
      survival time (ST(50)) of the knockout virus was significantly longer than the
      control virus. These results indicate that BM21 is not essential for virus
      replication in vitro, but that deletion of the gene delays the killing of the
      infected larvae.

PMID- 18343834
TI  - A viral histone H4 encoded by Cotesia plutellae bracovirus inhibits haemocyte
      spreading behaviour of the diamondback moth, Plutella xylostella.
AB  - Histone H4 is highly conserved and forms a central-core nucleosome with H3 in
      eukaryotic chromatin. Its covalent modification at the protruding N-terminal
      region from the nucleosomal core can change the chromatin conformation in order
      to regulate gene expression. A viral H4 was found in the genome of Cotesia
      plutellae bracovirus (CpBV). The obligate host of the virus is an endoparasitoid
      wasp, C. plutellae, which parasitizes the diamondback moth, Plutella xylostella,
      and interrupts host development and immune reactions. CpBV has been regarded as a
      major source for interrupting the physiological processes during parasitization.
      CpBV H4 shows high sequence identity with the amino acid sequence of P.
      xylostella H4 except for an extended N-terminal region (38 aa). This extended N
      terminal CpBV H4 contains nine lysine residues. CpBV H4 was expressed in P.
      xylostella parasitized by C. plutellae. Western blot analysis using a wide
      spectrum H4 antibody showed two H4s in parasitized P. xylostella. In parasitized
      haemocytes, CpBV H4 was detected predominantly in the nucleus and was highly
      acetylated. The effect of CpBV H4 on haemocytes was analysed by transient
      expression using a eukaryotic expression vector, which was injected into non
      parasitized P. xylostella. Expression of CpBV H4 was confirmed in the transfected
      P. xylostella by RT-PCR and immunofluorescence assays. Haemocytes of the
      transfected larvae lost their spreading ability on an extracellular matrix.
      Inhibition of the cellular immune response by transient expression was reversed
      by RNA interference using dsRNA of CpBV H4. These results suggest that CpBV H4
      plays a critical role in suppressing host immune responses during parasitization.

PMID- 18343835
TI  - Morpholino oligomers targeting the PB1 and NP genes enhance the survival of mice
      infected with highly pathogenic influenza A H7N7 virus.
AB  - Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) are single
      stranded nucleic acid-analogue antisense agents that enter cells readily and can
      reduce gene expression by steric blocking of complementary RNA (cRNA) sequences.
      Here, we tested a panel of PPMO designed to target conserved sequences in the RNA
      genome segments encoding polymerase subunits of a highly pathogenic mouse-adapted
      influenza A virus (SC35M; H7N7). Three PPMO, targeting the translation start site
      region of PB1 or NP mRNA or the 3'-terminal region of NP viral RNA (vRNA),
      potently inhibited virus replication in MDCK cells. Primer extension assays
      showed that treatment with any of the effective PPMO led to markedly reduced
      levels of mRNA, cRNA and vRNA. Initially, the potential toxicity of a range of
      intranasally administered PPMO doses was evaluated, by measuring their effect on
      body weight of uninfected mice. Subsequently, a non-toxic dosing regimen was used
      to investigate the effect of various PPMO on SC35M infection in a mouse model.
      Mice administered intranasal treatment of PPMO targeting the PB1-AUG region or NP
      vRNA, at 3 mug per dose, given once 3 h before and once 2 days after intranasal
      infection with 10xLD(50) of SC35M, showed a 2 log(10) reduction of viral titre in
      the lungs and 50 % survival for the 16 day duration of the experiment, whereas
      the NP-AUG-targeted PPMO treatment resulted in 30 % survival of an otherwise
      lethal infection. These data suggest that PPMO provide a useful reagent to
      investigate influenza virus molecular biology and may constitute a therapeutic
      strategy against highly pathogenic influenza viruses.

PMID- 18343836
TI  - Ecology of H3 avian influenza viruses in Korea and assessment of their pathogenic
      potentials.
AB  - To determine the genetic origins of novel H3 avian influenza viruses of chickens
      and ducks in Korea, genetic characterization of H3 avian influenza viruses
      isolated from live poultry markets and migratory aquatic birds in South Korea
      during 2004-2006 was conducted. Phylogenetic analysis revealed that at least four
      novel genotypes of H3N2 and two genotypes of H3N6 avian influenza viruses were co
      circulating in backyard poultry of Korea. The viruses were reassortants between
      H9N2 viruses of Korean chickens and unknown influenza viruses of migratory birds.
      Genetic comparison of H3 viruses from live bird markets with those from wild bird
      isolates revealed that certain gene segments of wild bird isolates are related
      closely to those of Korean group H9N2 viruses isolated from live poultry markets
      in 2003. Furthermore, animal-challenge studies demonstrated that the
      pathogenicity of certain avian H3 influenza viruses was altered due to
      reassortment, leading to H3 avian influenza viruses in Korea that can potentially
      expand their host range to include mammals. These studies emphasize the
      continuing need to monitor backyard poultry at live poultry markets to better
      understand interspecies transmission and the emergence of novel influenza viruses
      that have the potential to infect humans.

PMID- 18343837
TI  - Antibodies induced by the HA2 glycopolypeptide of influenza virus haemagglutinin
      improve recovery from influenza A virus infection.
AB  - The haemagglutinin (HA) of influenza A virus consists of two glycopolypeptides
      designated HA1 and HA2. Antibodies recognizing HA1 inhibit virus
      haemagglutination, neutralize virus infectivity and provide good protection
      against infection, but do not cross-react with the HA of other subtypes. Little
      is known regarding the biological activities of antibodies against HA2. To study
      the role of antibodies directed against HA2 during influenza virus infection, two
      vaccinia virus recombinants (rVVs) were used expressing chimeric molecules of HA,
      in which HA1 and HA2 were derived from different HA subtypes. The KG-11
      recombinant expressed HA1 from A/PR/8/34 (H1N1) virus and HA2 from A/NT/60 (H3N2)
      virus, whilst KG-12 recombinant expressed HA1 from A/NT/60 virus and HA2 from
      A/PR/8/34 virus. Immunization of BALB/c mice with rVV expressing HA2 of the HA
      subtype homologous to the challenge virus [A/PR/8/34 (H1N1) or A/Mississippi/1/85
      (H3N2)] did not prevent virus infection, but nevertheless resulted in an increase
      in mice survival and faster elimination of virus from the lungs. Passive
      immunization with antibodies purified from mice immunized with rVVs confirmed
      that antibodies against HA2 were responsible for the described effect on virus
      infection. Based on the facts that HA2 is a rather conserved part of the HA and
      that antibodies against HA2, as shown here, may moderate virus infection, future
      vaccine design should deal with the problem of how to increase the HA2 antibody
      response.

PMID- 18343838
TI  - Protection of cats against lethal influenza H5N1 challenge infection.
AB  - Highly pathogenic avian influenza virus (HPAIV) H5N1 of Asian origin continues to
      circulate in poultry and wild birds, causing considerable concern for veterinary
      and public health in Asia, Europe and Africa. Natural transmission of HPAIV H5N1
      from poultry to humans, resulting in infections associated with high mortality,
      and from poultry or wild birds to large felids and domestic cats has been
      reported. Experimental infection of cats with HPAIV H5N1 derived from a human
      patient resulted in lethal disease. The role of cats in the adaptation of HPAIV
      H5N1 to mammals and vaccination regimens for the eventual protection of cats,
      however, remain to be elucidated. Here, it was shown that cats can be protected
      against a lethal high-dose challenge infection by an inactivated, adjuvanted
      heterologous H5N6 avian influenza virus vaccine. The challenge HPAIV H5N1 was
      derived from a naturally infected cat. In non-vaccinated cats, low-dose exposure
      resulted in asymptomatic infections with minimal virus excretion. As diseased
      cats can transmit the infection to naive contact animals, the epidemiological
      role of H5N1-infected cats in endemically infected areas as a link between wild
      birds, poultry and humans needs close inspection, and vaccination of cats should
      be considered to reduce possible human exposure.

PMID- 18343839
TI  - Specificity and functional interaction of the polymerase complex proteins of
      human and avian metapneumoviruses.
AB  - Human metapneumovirus (HMPV) and avian metapneumovirus (AMPV) have a similar
      genome organization and protein composition, but a different host range. AMPV
      subgroup C (AMPV-C) is more closely related to HMPV than other AMPVs. To
      investigate the specificity and functional interaction of the polymerase complex
      proteins of human and avian metapneumoviruses, a minireplicon system was
      generated for AMPV-C and used in combination with minireplicon systems for HMPV
      lineages A1 and B1. Viral RNA-like molecules representing HMPV-A1 and -B1, AMPV-A
      and -C and human respiratory syncytial virus were replicated efficiently by
      polymerase complexes of HMPV-A1 and -B1 and AMPV-C, but not by polymerase
      complexes of bovine parainfluenza virus 3. Upon exchange of HMPV and AMPV-C
      polymerase complex components, all chimeric polymerase complexes were functional;
      exchange between HMPVs did not result in altered polymerase activity, whereas
      exchange between HMPVs and AMPV-C did. Recombinant HMPV-B1 viruses in which
      polymerase genes were exchanged with those of HMPV-A1 replicated with normal
      kinetics in vitro, whilst replacement with AMPV-C genes resulted in moderate
      differences in virus replication. In hamsters, recombinant HMPV-B1 viruses in
      which individual polymerase genes were exchanged with those of AMPV-C were
      attenuated, irrespective of the results obtained with minireplicon systems or in
      vitro replication assays. This study provides insight into the specificity and
      functional interaction of polymerase complex proteins of human and avian
      metapneumoviruses, but neither minireplicon systems nor in vitro replication
      kinetics were found to be predictive for attenuation in permissive animals.

PMID- 18343840
TI  - Measles virus inhibits human immunodeficiency virus type 1 reverse transcription
      and replication by blocking cell-cycle progression of CD4+ T lymphocytes.
AB  - Acute measles virus (MV) infection results in a decrease in plasma human
      immunodeficiency virus type 1 (HIV-1) RNA levels in co-infected children. An in
      vitro peripheral blood mononuclear cell (PBMC) culture system was used to assess
      the mechanisms by which MV blocks HIV-1 replication. MV inhibited proliferation
      of CD4(+) T lymphocytes, the target cell for HIV-1 replication. In the presence
      of MV, cells did not progress to G(1b) and S phases, steps critical for the
      completion of HIV-1 reverse transcription and productive replication. This block
      in cell-cycle progression was characterized by an increased proportion of CD4(+)
      and HIV-1-infected cells retained in the parental generation in PBMCs co-cultured
      with MV and HIV-1, and decreased levels of cyclins and RNA synthesis. Early HIV-1
      replication was also inhibited in the presence of MV, as measured by reduced
      expression of a luciferase reporter gene and lower levels of both early (LTR) and
      late (LTR-gag) DNA intermediates of HIV-1 reverse transcription in the presence
      of CCR5-tropic HIV-1. The effects of MV on lymphoproliferation and p24 antigen
      production were reproduced by n-butyrate and hydroxyurea, drugs that block the
      cell cycle in G(1a) and G(1)/S, respectively. It was concluded that MV inhibits
      HIV-1 productive replication in part by blocking the proliferation of CD4(+) T
      lymphocytes.

PMID- 18343841
TI  - Effect of NS3 and NS5B proteins on classical swine fever virus internal ribosome
      entry site-mediated translation and its host cellular translation.
AB  - A full-length NS3 (NS3F) and a truncated NS3 protein (NS3H) with an RNA helicase
      domain possess RNA helicase activity. Using an in vitro system with a
      monocistronic reporter RNA or DNA, containing the CSFV 5'-UTR, we observed that
      both NS3F and NS3H enhanced internal ribosome entry site (IRES)-mediated and
      cellular translation in a dose-dependent manner, but NS3 protease (NS3P) that
      lacks a helicase domain did not. NS3F was stronger than NS3H in promoting both
      translations. These results showed that viral RNA helicase could promote viral
      and cellular translation, and higher RNA helicase activity might be more
      efficient. The NS5B protein, the viral replicase, did not significantly affect
      the IRES-directed or cellular translation alone. NS5B significantly enhanced the
      stimulative effect of NS3F on both IRES-mediated and cellular translation, but
      did not affect that of NS3H or NS3P. This suggests that NS5B and NS3 interact via
      the protease domain during the enhancement of translation.

PMID- 18343842
TI  - Thiopurines inhibit bovine viral diarrhea virus production in a thiopurine
      methyltransferase-dependent manner.
AB  - The family Flaviviridae comprises positive-strand RNA viral pathogens of humans
      and livestock with few treatment options. We have previously shown that
      azathioprine (AZA) has in vitro activity against bovine viral diarrhea virus
      (BVDV). While the mechanism of inhibition is unknown, AZA and related thiopurine
      nucleoside analogues have been used as immunosuppressants for decades and both
      AZA metabolites and cellular genes involved in AZA metabolism have been
      extensively characterized. Here, we show that only certain riboside metabolites
      have antiviral activity and identify the most potent known antiviral AZA
      metabolite as 6-methylmercaptopurine riboside (6MMPr). The antiviral activity of
      6MMPr is antagonized by adenosine, and is specific to BVDV and not to the related
      yellow fever virus. An essential step in the conversion of AZA to 6MMPr is the
      addition of a methyl group onto the sulfur atom attached to position six of the
      purine ring. Intracellularly, the methyl group is added by thiopurine
      methyltransferase (TPMT), an S-adenosyl methionine-dependent methyltransferase.
      Either chemically bypassing or inhibiting TPMT modulates antiviral activity of
      AZA metabolites. TPMT exists in several variants with varying levels of activity
      and since 6MMPr is a potent antiviral, the antiviral activity of AZA may be
      modulated by host genetics.

PMID- 18343843
TI  - Mutagenesis of the West Nile virus NS2B cofactor domain reveals two regions
      essential for protease activity.
AB  - The flavivirus NS2B/NS3 protease has received considerable attention as a target
      for the development of antiviral compounds. While substrate based inhibitors have
      been the primary focus to date, an approach focussing on NS2B cofactor
      displacement could prove to be an effective alternative. To understand better the
      role of the NS2B cofactor in protease activation, we conducted an alanine
      mutagenesis screen throughout the 42-residue central cofactor domain (NS2B(51
      92)) of West Nile virus (WNV). Two sites critical for proteolytic activity were
      identified (NS2B(59-62) and NS2B(75-87)), where the majority of substitutions
      were found to significantly decrease proteolytic activity of a recombinant WNV
      NS2B/NS3 protease. These findings provide mechanistic insights into the
      structural and functional role that the cofactor may play in the substrate-bound
      and free protease complexes as well as providing novel sites for targeting new
      antiviral inhibitors.

PMID- 18343844
TI  - Identification of residues in the receptor-binding domain (RBD) of the spike
      protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor
      interaction.
AB  - Human coronavirus NL63 (NL63), a member of the group I coronaviruses, may cause
      acute respiratory diseases in young children and immunocompromised adults. Like
      severe acute respiratory syndrome coronavirus (SARS-CoV), NL63 also employs the
      human angiotensin-converting enzyme 2 (hACE2) receptor for cellular entry. To
      identify residues in the spike protein of NL63 that are important for hACE2
      binding, this study first generated a series of S1-truncated variants, examined
      their associations with the hACE2 receptor and subsequently mapped a minimal
      receptor-binding domain (RBD) that consisted of 141 residues (aa 476-616) towards
      the C terminus of the S1 domain. The data also demonstrated that the NL63 RBD
      bound to hACE2 more efficiently than its full-length counterpart and had a
      binding efficiency comparable to the S1 or RBD of SARS-CoV. A further series of
      RBD variants was generated using site-directed mutagenesis and random mutant
      library screening assays, and identified 15 residues (C497, Y498, V499, C500,
      K501, R518, R530, V531, G534, G537, D538, S540, E582, W585 and T591) that
      appeared to be critical for the RBD-hACE2 association. These critical residues
      clustered in three separate regions (designated RI, RII and RIII) inside the RBD,
      which may represent three receptor-binding sites. These results may help to
      delineate the molecular interactions between the S protein of NL63 and the hACE2
      receptor, and may also enhance our understanding of the pathogenesis of NL63 and
      SARS-CoV.

PMID- 18343845
TI  - Analysis of the mechanism of antibody-dependent enhancement of feline infectious
      peritonitis virus infection: aminopeptidase N is not important and a process of
      acidification of the endosome is necessary.
AB  - Infection of the monocyte/macrophage lineage with feline infectious peritonitis
      virus (FIPV) is enhanced in the presence of anti-FIPV antibodies (antibody
      dependent enhancement or ADE). We investigated the following unclear points
      concerning ADE of FIPV infection: (i) involvement of the virus receptor, feline
      aminopeptidase N (fAPN), in ADE activity in FIPV infection; (ii) necessity of
      acidification of the endosome in cellular invasion of FIPV. Virus receptor
      blocking experiments using anti-fAPN antibodies at 4 or 37 degrees C and
      experiments using fAPN-negative U937 cells revealed that fAPN is not involved in
      ADE of FIPV infection. Experiments using lysosomotropic agents clarified that
      acidification of the endosome is necessary for cellular invasion by FIPV,
      regardless of the presence or absence of antibodies. These findings may be very
      important for understanding the mechanism of ADE of FIPV infection.

PMID- 18343846
TI  - Widespread recombination within human parechoviruses: analysis of temporal
      dynamics and constraints.
AB  - Human parechoviruses (HPeVs), members of the family Picornaviridae, are
      classified into six types. To investigate the dynamics and likelihood of
      recombination among HPeVs, we compared phylogenies of two distant regions (VP1
      and 3Dpol) of 37 HPeV isolates (types 1 and 3-5) and prototype sequences (types 1
      6). Evidence for frequent recombination between HPeV1, 4, 5 and 6 was found. The
      likelihood of recombination was correlated with the degree of VP1 divergence and
      differences in isolation dates, both indicative of evolutionary times of
      divergence. These temporal dynamics were found to be most similar to those of
      human enterovirus species B variants. In contrast, HPeV3 remained
      phylogenetically distinct from other types throughout the genome. As HPeV3 is
      equally divergent in nucleotide sequence from the other HPeV types, its genetic
      isolation may reflect different biology and changed cellular tropisms, arising
      from the deletion of the RGD motif, and likely use of a non-integrin receptor.

PMID- 18343847
TI  - Occurrence, function and evolutionary origins of '2A-like' sequences in virus
      genomes.
AB  - 2A is an oligopeptide sequence mediating a ribosome 'skipping' effect, producing
      an apparent 'cleavage' of polyproteins. First identified and characterized in
      picornaviruses, '2A-like' sequences are found in other mammalian viruses and a
      wide range of insect viruses. Databases were analysed using a motif conserved
      amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were
      inserted into a reporter polyprotein to determine their cleavage activity. Our
      analyses showed that these sequences fall into two categories. The majority
      mediated very high (complete) cleavage to separate proteins and a few sequences
      mediated cleavage with lower efficiency, generating appreciable levels of the
      uncleaved form. Phylogenetic analyses of 2A-like sequences and RNA-dependent RNA
      polymerases (RdRps) indicated multiple, independent, acquisitions of these
      sequences at different stages during virus evolution. Within a virus family, 2A
      sequences are (probably) homologous, but diverge due to other evolutionary
      pressures. Amongst different families, however, 2A/2A-like sequences appear to be
      homoplasic.

PMID- 18343848
TI  - Naturally arising point mutations in non-essential domains of equine infectious
      anemia virus Rev alter Rev-dependent nuclear-export activity.
AB  - Equine infectious anemia virus (EIAV) exhibits a high rate of genetic variation
      in vivo, and results in a clinically variable disease in infected horses. In vivo
      populations of EIAV have been characterized by the presence of distinct, genetic
      subpopulations of Rev that differ in phenotype and fluctuate in dominance in a
      manner coincident with each clinical stage of disease. This study examined the
      specific mutations that arose in vivo and altered the phenotype. The Rev protein
      was found to be highly conserved, and only 10 aa mutations were observed at a
      frequency greater than 10 % in the sample population. Nine of these mutations
      were capable of significantly altering Rev activity, either as single mutations
      in the context of the founder variant, or in the context of cumulatively fixed
      mutations. The results indicated that limited genetic variation outside the
      essential functional domains of Rev can alter the phenotype and may confer a
      selective advantage in vivo.

PMID- 18343849
TI  - The block to membrane fusion differs with the site of ligand insertion in
      modified retroviral envelope proteins.
AB  - Efforts to achieve cell type-specific transduction of retroviral vectors for gene
      therapy have centred on modification of the envelope protein (Env). Typically,
      addition of a ligand to Env gives binding to the new or target receptor, but
      little or no infection, and affects the subunit association of the modified Env.
      We previously discovered two point mutations that increase targeted infection by
      over 1000-fold when added to an Env modified by N-terminal insertion of the
      receptor-binding domain from amphotropic murine leukemia virus Env. Here, we
      asked whether these mutations would similarly increase transduction by Env
      modified with a clinically relevant ligand, human interleukin-13 (IL-13L).
      Addition of the point mutations stabilized the weak subunit association observed
      in some IL-13L-modified Env proteins, but infection via the target IL-13 receptor
      still did not occur. Fluorescence-based cell-cell fusion assays and studies with
      a membrane-curving agent revealed that defects in membrane fusion differed with
      the site of ligand insertion. When IL-13 was inserted into the N terminus of Env,
      membrane fusion was blocked prior to membrane-lipid mixing, regardless of whether
      flanking flexible linkers were added. Unexpectedly, insertion of IL-13 in the
      proline-rich region showed evidence of initiation of fusion and fusion-peptide
      exposure, but fusion was blocked at a subsequent step prior to fusion-pore
      formation. Thus, the site of ligand insertion influenced initiation of membrane
      fusion and its progression. These observations suggest that a novel site for
      ligand insertion must be identified before clinically useful targeted
      transduction will be achieved.

PMID- 18343850
TI  - Characterization of interleukin-1beta mRNA expression in chicken macrophages in
      response to avian reovirus.
AB  - Inhibitors of viral disassembly or RNA and protein synthesis, viral disassembly
      intermediates (infectious subviral particles, ISVP), binary ethylenimine
      inactivated virions, and viral particles lacking genomic double-stranded (ds) RNA
      (empty particles) were used to assess the expression of interleukin-1beta (IL
      1beta) mRNA in chicken (chIL-1beta) macrophages in response to avian reovirus.
      The results demonstrate that two distinct expression patterns of chIL-1beta mRNA
      mediated by different steps in viral replication were found. Viral disassembly
      was required for the induction of a rapid, transient expression pattern of chIL
      1beta mRNA that was rapidly induced at 30 min, with maximal levels reached by 2
      h, and fell to a low level within 6 h post-inoculation, while viral RNA synthesis
      rather than protein translation, which was subsequent to membrane penetration,
      was required to induce a stable, sustained expression pattern of chIL-1beta mRNA
      that occurred at and after 6 h post-inoculation. In addition, the induction of
      chIL-1beta mRNA expression by the empty particles and ISVP was extremely weak,
      compared with the active dsRNA(+) virions or binary ethylenimine-inactivated
      virions, suggesting that the presence of dsRNA, even if transcriptionally
      inactive, may be an important factor in this response.

PMID- 18343851
TI  - Association of the transcriptional response of soybean plants with soybean mosaic
      virus systemic infection.
AB  - Compatible virus infection induces and suppresses host gene expression at the
      global level. These gene-expression changes are the molecular basis of symptom
      development and general stress and defence-like responses of the host. To assess
      transcriptional changes in soybean plants infected with soybean mosaic virus
      (SMV), the first soybean trifoliate leaf, immediately above the SMV-inoculated
      unifoliate leaf, was sampled at 7, 14 and 21 days post-inoculation (p.i.) and
      subjected to microarray analysis. The identified changes in gene expression in
      soybean leaves with SMV infection at different time points were associated with
      the observed symptom development. By using stringent selection criteria (>or=2-
      or <or=-2-fold change and a Q value of <or=0.05), 273 (1.5 %) and 173 (0.9 %)
      transcripts were identified to be up- and downregulated, respectively, from 18
      613 soybean cDNAs on the array. The expression levels of many transcripts
      encoding proteins for hormone metabolism, cell-wall biogenesis, chloroplast
      functions and photosynthesis were repressed at 14 days p.i. and were associated
      with the highest levels of viral RNA in the host cells. A number of transcripts
      corresponding to genes involved in defence were either downregulated or not
      affected at the early stages of infection, but upregulated at the late stages,
      indicating that the plant immune response is not activated until the late time
      points of infection. Such a delayed defence response may be critical for SMV to
      establish its systemic infection.

PMID- 18343852
TI  - Rapid evolutionary dynamics of zucchini yellow mosaic virus.
AB  - Zucchini yellow mosaic virus (ZYMV) is an economically important virus of
      cucurbit crops. However, little is known about the rate at which this virus has
      evolved within members of the family Cucurbitaceae, or the timescale of its
      epidemiological history. Herein, we present the first analysis of the
      evolutionary dynamics of ZYMV. Using a Bayesian coalescent approach we show that
      the coat protein of ZYMV has evolved at a mean rate of 5.0 x 10(-4) nucleotide
      substitutions per site, per year. Notably, this rate is equivalent to those
      observed in animal RNA viruses. Using the same approach we show that the lineages
      of ZYMV sampled here have an ancestry that dates back no more than 800 years,
      suggesting that human activities have played a central role in the dispersal of
      ZYMV. Finally, an analysis of phylogeographical structure provides strong
      evidence for the in situ evolution of ZYMV within individual countries.

PMID- 18343853
TI  - A species barrier limits transmission of chronic wasting disease to mink (Mustela
      vison).
AB  - Transmissible mink encephalopathy (TME) occurs as sporadic outbreaks associated
      with ingestion of feed presumably contaminated with some type of prion disease.
      Mink lack a species barrier to primary oral challenge with bovine spongiform
      encephalopathy, whereas they have a barrier to such challenge with scrapie. We
      investigated whether mink have a species barrier to chronic wasting disease (CWD)
      by performing primary intracerebral (IC) and primary oral challenge with CWD
      positive elk brain. Primary IC challenge resulted in clinical disease in two of
      eight mink at 31-33 months incubation. Affected mink had spongiform vacuolation
      and astrocytosis within the central nervous system and immunoreactivity to
      disease-associated prion protein (PrP(d)) in brain, retina and lymph node. CWD IC
      recipients had significantly lower brain vacuolation and PrP(d) deposition
      scores, significantly lower cerebrocortical astrocyte counts and significantly
      higher hippocampal astrocyte counts than TME IC recipients. Primary oral
      challenge with CWD-positive elk brain (n=22) or with CWD-negative elk brain given
      IC (n=7) or orally (n=23) did not result in clinical or microscopic abnormalities
      during 42 months observation. Novel prion gene polymorphisms were identified at
      codon 27 (arginine/tryptophan) and codon 232 (arginine/lysine). This study shows
      that, whilst CWD can cause disease when given IC to mink, the lesions are not
      characteristic of TME, transmission is inefficient compared with TME and oral
      challenge does not result in disease. The demonstration of a species barrier in
      cervid-to-mustelid prion transmission indicates that mink are unlikely to be
      involved in natural CWD transmission.

PMID- 18343854
TI  - International correlations between indicators of prevalence, hospital admissions
      and mortality for asthma in children.
AB  - BACKGROUND: There are extensive data on the prevalence of childhood asthma world
      wide but the relationships between asthma symptom prevalence, mortality and
      hospital admissions have not been investigated. METHODS: The International Study
      of Asthma and Allergies in Childhood (ISAAC) used a standard questionnaire to
      measure the 12-month period prevalence of asthma symptoms by parental report in 6
      7 year olds in 40 countries, and by self-report in 13-14 year olds in 60
      countries. The initial survey was in the mid 1990s (Phase One) and this was
      repeated in the early 2000s (Phase Three). We correlated the prevalence values of
      any wheeze and severe wheeze with national data on mortality and hospital
      admissions for asthma in 5-14 year olds. RESULTS: All correlations with
      prevalence were positive. In 13-14 year olds, the correlations between severe
      wheeze in Phase One and contemporaneous mortality and hospital admission rates
      were r = 0.32 (P = 0.047) and r = 0.73 (P = 0.003), respectively. In 6-7 year
      olds in Phase One, the correlation with severe wheeze and mortality was r = 0.42
      (P = 0.024). In 14 countries the correlation between admission and mortality
      rates in the 5-14 year age group was r = 0.53 (P = 0.054). CONCLUSIONS: There are
      consistently positive associations between asthma symptom prevalence, admissions
      and mortality. The prevalence of asthma symptoms in children obtained from local
      questionnaire studies may provide a guide to estimate the incidence of severe
      episodes of asthma in countries with incomplete data on hospital admissions or
      mortality, or vice versa.

PMID- 18343856
TI  - Associations between subjective night sweats and sleep study findings.
AB  - BACKGROUND: In 2 previous studies, patients reporting night sweats were found to
      be more likely to have other sleep-related symptoms. Sleep apnea is often
      mentioned as a possible cause of night sweats, but there is little evidence to
      support this assertion. METHODS: Retrospective review of data from 2 sleep
      laboratories in Oklahoma City, Oklahoma. Analyses included bivariate and
      multivariate tests of associations between reported night sweats and other sleep
      related symptoms, scores on specific sleep inventories, and findings from
      polysomnography. RESULTS: Patients who reported night sweats were more likely to
      report daytime fatigue (P = .001); creepy/crawly feelings in their legs (P =
      .003); kicking during sleep (P = .004); snoring (P = .03); nighttime breathing
      trouble (P < .0001); awakening in the night with aches and pains (P < .0001); and
      waking in the morning with a headache (P = .0002) and still tired (P = .002) as
      compared with those who did not report night sweats. They also had higher mean
      scores on the Epworth Sleepiness Scale (P < .0001). However, there was no
      statistically significant association between reported night sweats and sleep
      onset latency, arousal index, apnea hypopnea index, periodic leg movement index,
      or total sleep time. CONCLUSIONS: Subjective night sweats are associated with a
      variety of other sleep-related symptoms, but we could find no evidence for an
      association between subjective night sweats and objective evidence of specific
      sleep disorders.

PMID- 18343857
TI  - 2002 ACC/AHA guideline versus clinician judgment as diagnostic tests for chest
      pain.
AB  - PURPOSE: Hospital admissions for chest pain are frequent and costly. The use of
      objective criteria to determine the need for hospitalization may save money. Here
      we compare the 2002 American College of Cardiology/American Heart Association
      (ACC/AHA) guidelines for the management of patients with unstable angina and
      nonST-segment elevation myocardial infarction to clinical judgment as diagnostic
      tests to predict which patients with chest pain will develop positive cardiac
      troponin-I. METHODS: Researchers conducted a retrospective chart review of
      patients admitted to a military community hospital for chest pain over a 2-year
      period. The study determined sensitivity and specificity for both the ACC/AHA
      guidelines and consensus of clinical judgment to predict which subjects would
      develop positive cardiac troponin-I. RESULTS: Positive cardiac troponin-I was
      very low (7 of 386). Both the ACC/AHA guidelines and clinical judgment had
      sensitivities of 100% (95% CI, 65-100) to predict positive cardiac troponin-I.
      The ACC/AHA guideline was 13% specific (95% CI, 12-13), with clinical judgment at
      48% (95% CI, 47-48). Classification as low risk had a high negative predictive
      value (ACC/AHA guideline, 1.00 [95% CI, 0.95-1.00]; clinical judgment, 1.00 [95%
      CI, 0.99-1.00]). CONCLUSION: Patients categorized as low risk by either method
      could probably be discharged from the emergency department without developing
      positive troponin-I.

PMID- 18343858
TI  - Quality of life associated with daily opioid therapy in a primary care chronic
      pain sample.
AB  - BACKGROUND: Daily opioid therapy is widely used in the treatment of chronic
      noncancer pain, yet there is limited empirical evidence on the relationship of
      opioid dosing and health-related quality of life (HRQoL) in primary care
      settings. METHODS: An analysis was conducted to assess the relationship of opioid
      dose to quality of life. The sample consisted of 801 chronic pain patients who
      were prescribed daily opioids and 93 nonopioid users recruited from the practices
      of 235 primary care physicians. Eight HRQoL domain scores were calculated and
      compared with US norms and across opioid use groups. A new modeling technique,
      propensity score matching analysis, was performed to adjust for potential
      confounding factors across 4 morphine-equivalent opioid dose groups (<20 mg, 20
      40 mg, 41-105 mg, >105 mg). RESULTS: HRQoL scores were significantly lower in
      chronic noncancer pain patients relative to the US general population regardless
      of opioid use. In unadjusted comparisons, those using up to 20 mg/d of opioids
      had the highest HRQoL scores, whereas those using >105 mg/d had the lowest. After
      adjusting for potential confounders, those in the 20 mg to 40 mg/d dosing group
      had significantly better HRQoL scores than their nonopioid-treated or higher
      dosed counterparts. CONCLUSION: Use of low- to moderate-dose opioid therapy
      provides an improvement in HRQoL scores for chronic noncancer pain patients
      compared to no opioid therapy, while high-dose opioids have a smaller positive
      effect that is limited to mental health quality of life and patient satisfaction,
      and that may not justify treatment.

PMID- 18343859
TI  - Clinician-patient communication about physical activity in an underserved
      population.
AB  - BACKGROUND: The 5A (Ask, Advise, Agree, Assist, Arrange) model, used to promote
      patient behavior changes in primary care, can also be applied to physical
      activity. Our goal was to assess primary care physicians' use of the 5A model in
      discussions with underserved populations about physical activity. METHODS: We
      analyzed 51 audio-recorded, transcribed office visits on randomly selected
      patient care days and after-visit patient surveys with adults in 2 community
      health centers in Rochester, New York. RESULTS: The patient sample was 51%
      African-American and predominantly female (70%), with the majority having a high
      school-level education or less (66%) and an annual household income < dollars
      39,000 (57%). Physical activity was discussed during 19 of the 51 visits, which
      included 16 (84%) visits with "Ask"; 10 (53%) with "Advise"; 4 (21%) with
      "Agree"; 5 (26%) with "Assist"; and 0 with "Arrange" statements. Most discussions
      of physical activity contained several Ask or Advise statements but few Agree,
      Assist, or Arrange statements. CONCLUSION: Communication about physical activity
      that included Agree, Arrange, and Assist statements of the 5A model was
      infrequent. Health promotion interventions in underserved populations should
      target these steps and prompt patients to initiate communication to improve
      physical activity.

PMID- 18343860
TI  - Factors affecting Latino adults' use of antibiotics for self-medication.
AB  - BACKGROUND: Recent data has suggested the use of antibiotics acquired without a
      prescription by Latinos in the United States. We explored Latino adults'
      experience in treating common infections particularly in regards to self
      medication with antibiotics. METHODS: We conducted 3 focus groups (n = 28) in
      Charleston, South Carolina, with Latino adults (>or=18 years of age) recruited
      throughout the community: 12 women and 16 men, ranging in age from 18 to 52
      years. All of the participants were immigrants, 89% noted Mexico as their country
      of origin. Focus groups were conducted in Spanish and audiotaped. Transcripts
      were translated into English and then translated back to Spanish to assure
      consistency of the language. Themes were identified using an editing style.
      RESULTS: Participants' previous experiences in countries with limited
      restrictions on antibiotics influenced acquisition of antibiotics without a
      prescription in the United States. Participants believed that physician visits
      for a diagnosis and prescription were unnecessary when the patient was familiar
      with the symptom and it had previously responded to antibiotic treatment. Access
      to care was not reported to be a significant barrier to a physician visit when
      individuals felt they were "sick" or children were the patients. Participants
      reported using local tiendas (small stores in Latino neighborhoods that sell
      ethnically consistent and imported products) and importation of medication to
      meet their need for self-medication with antibiotics. The role of self-medication
      in the development of antibiotic resistance was essentially unknown among the
      participants. CONCLUSIONS: Successful interventions to improve use of antibiotics
      need to be culturally sensitive to specific attitudes and behaviors found in the
      Latino population.

PMID- 18343861
TI  - Preventing or improving obesity by addressing specific eating patterns.
AB  - The problem of obesity and overweight is an epidemic in the United States. Weight
      is a product of energy balance: energy intake versus energy expenditure. The
      purpose of this review is to identify adult eating behaviors that are known to
      strongly affect the energy intake side of the energy balance and that may be
      readily amenable to prevention and intervention efforts in primary care.
      Restaurant and fast food consumption, large portion sizes, and consumption of
      beverages with sugar added increase energy intake and are highly associated with
      weight gain and obesity. Conversely, consumption of low energy dense food, ie,
      fruits and vegetables, and routine healthy breakfast consumption can help to
      maintain or lose weight. These distinct behaviors represent concrete negative and
      positive eating patterns on which primary care providers can focus when
      counseling overweight and obese patients. They also represent behavioral targets
      for designing and testing clinical interventions.

PMID- 18343862
TI  - How is your sleep: a neglected topic for health care screening.
AB  - PURPOSE: Inadequate sleep, whether it is caused by voluntary sleep curtailment or
      specific sleep disorders, is highly prevalent, has wide-ranging negative
      consequences for human health and well-being, and is greatly under-diagnosed. The
      objective of this study was to determine the frequency of inquiry by family
      medicine clinics about unhealthy sleep patterns and symptoms in their health
      history database questionnaires. METHODS: This study surveyed health history
      database forms used by family medicine clinics in the 7-county Minneapolis/St.
      Paul metropolitan area for questions related to sleep disorders. Fourteen
      distinct database batteries that are used in 121 primary care clinics and employ
      935 family medicine doctors (roughly 75% of physicians practicing in this region)
      were analyzed. RESULTS: Direct questions about sleep health are often not
      included in health history questionnaires. Eight of 14 (57%) database batteries
      reviewed in this study featured no sleep-related questions. Other lifestyle
      issues were screened with much greater frequency. For example, questions about
      healthy eating patterns and regular physical activity were present in 13 and 12
      of the 14 batteries (93% and 86%), respectively. CONCLUSIONS: Despite the
      significant burden that sleep disorders place on human health, this study found
      that family medicine clinics do not screen for them as frequently as they do for
      other lifestyle/behavioral issues when they establish a health history database
      for new patients.

PMID- 18343863
TI  - The management of keloids: hands-on versus hands-off.
AB  - Keloids are benign fibrous growths that appear in scar tissue. The lesions can be
      severely disfiguring and early recognition of genetic lesions is crucial. This
      case report outlines and reviews the important management strategies for these
      lesions and the requirement for extensive counseling for the patient and their
      family. Many potential medical and surgical interventions exist. Unfortunately,
      these lesions tend to recur and overall outcomes remain poor. Given patient
      susceptibility to disfiguring results, surgical intervention should be used with
      extreme caution.

PMID- 18343864
TI  - Serum chromium and gestational diabetes.
AB  - OBJECTIVE: To prospectively assess if chromium levels are different in
      gestational diabetics than in nondiabetic pregnant women. Therapeutic options
      could exist if levels are different. METHODS: We conducted a 2-year prospective,
      gestational cohort study. The cohort included newly diagnosed pregnant patients.
      Two blood samples were taken, the first at consent, the second at the time of
      diabetes screening. RESULTS: Five hundred eighty patients entered the cohort. One
      hundred fifty-five were lost to follow up and 425 patients completed the study
      (396 nondiabetics and 29 diabetics). The patients with gestational diabetes were
      significantly older, with a family history of gestational diabetes, and were
      significantly more likely to have been a gestational diabetic in a previous
      pregnancy (P < 05). There was no significant difference between the 2 groups for
      chromium levels both at enrollment (0.15 +/- 0.06 ng/mL vs 0.14 +/- 0.03 ng/mL; P
      = .28) and during the second trimester (0.14 +/- 0.06 ng/mL vs 0.14 +/- 0.04
      ng/mL; P = .82). CONCLUSION: Serum chromium levels do not exhibit any significant
      variation between gestational diabetic women and nondiabetic women when assessed
      prospectively.

PMID- 18343865
TI  - Brucellosis and sacroiliitis: a common presentation of an uncommon pathogen.
AB  - Musculoskeletal problems are the most common chief complaint in ambulatory
      medicine across all specialties, and back pain is one of the top 10 problems
      encountered by the general practitioner. The differential diagnosis of lower back
      pain is exhaustive, but a history significant for constitutional symptoms or
      unusual exposures should prompt a work-up for an infectious cause. We describe
      the case of a 25-year-old man with a Brucella abortus sacroiliitis and possible
      orchiitis after consumption of unpasteurized cheese imported from El Salvador.
      The patient was successfully treated with gentamycin, rifampin, and doxycycline.
      Though the presentations of brucellosis are myriad, osteoarticular involvement of
      the axial skeleton is the most common presentation of this zoonotic infection. In
      the United States brucellosis is rarely encountered and is typically limited to
      people who are exposed during travel to endemic areas. Here we review briefly the
      epidemiology and presentation of a Brucella infection and current recommendations
      for treatment.

PMID- 18343866
TI  - Patient attitudes toward early abortion services in the family medicine clinic.
AB  - PURPOSE: To examine urban, inner-city female patients' acceptability of the
      provision of early abortion services by their family physician in the family
      medicine clinic (FMC). METHODS: We administered a survey with open- and closed
      ended questions to a convenience sample of English- or Spanish-speaking female
      patients aged 18 to 45 recruited from a FMC in the Bronx, New York. Responses
      were analyzed using quantitative and qualitative methods. RESULTS: One hundred
      forty-eight women completed the survey. The majority of respondents stated the
      FMC should offer abortion services. Seventy percent agreed their clinic should
      provide medication abortion, and 47% agreed their clinic should provide suction
      abortion. Of those who would personally consider an abortion, 73% responded that
      they would prefer to have it done by their family physician in the FMC, whereas
      22% would prefer it at a freestanding, high-volume abortion clinic, and 5% had no
      preference. CONCLUSIONS: The majority of patients surveyed accepted the
      integration of abortion services into our FMC setting, and would choose to have
      an early abortion at their FMC. Increasing options for abortion provision within
      our FMC was acceptable to the majority of our sample.

PMID- 18343867
TI  - Body composition and physical fitness in a cohort of US military medical
      students.
AB  - Medical school requires that students balance academic schedules with other
      lifestyle demands, including nutrition, physical fitness, and wellness. We
      retrospectively reviewed trends in body composition and physical fitness of a
      cohort of military medical students attending the Uniformed Services University.
      Although students were able to maintain muscular endurance and body composition,
      cardiorespiratory endurance, as measured by a timed 1.5-mile run, declined
      significantly over a 2-yr period.

PMID- 18343869
TI  - Antimicrobial storage and antibiotic resistance.

PMID- 18343870
TI  - African family medicine.

PMID- 18343871
TI  - Integrative medicine increasing in family medicine residency programs.

PMID- 18343873
TI  - The case for a broad base.

PMID- 18343874
TI  - Establishment of cell-cell junctions depends on the oligomeric states of VE
      cadherin.
AB  - Specifically expressed at intercellular adherens junctions of endothelial cells,
      VE-cadherin is a receptor that exhibits particular self-association properties.
      Indeed, in vitro studies demonstrated that the extracellular part of VE-cadherin
      elaborates Ca(++)-dependent hexameric structures. We hypothesized that this
      assembly could be at the basis of a new cadherin-mediated cell-cell adhesion
      mechanism. To verify this assumption, we first demonstrated that VE-cadherin can
      elaborate hexamers at the cell surface of confluent endothelial cells. Second,
      mutations were introduced within the extracellular part of VE-cadherin to
      destabilize the hexamer. Following an in vitro screening, three mutants were
      selected, among which, one is able to elaborate only dimers. The selected
      mutations were expressed as C-terminal green fluorescent protein fusions in CHO
      cells. Despite their capacity to elaborate nascent cell-cell contacts, the
      mutants seem to be rapidly degraded and/or internalized. Altogether, our results
      suggest that the formation of VE-cadherin hexamers protects this receptor and
      might allow the elaboration of mature endothelial cell-cell junctions.

PMID- 18343875
TI  - In vitro formation of a novel type of membrane vesicles containing Dpm1p:
      putative transport vesicles for lipid droplets in budding yeast.
AB  - A novel type of membrane vesicles was formed in vitro from microsomes of
      Saccharomyces cerevisiae, which carries Dpm1p, an enzyme involved in dolichol
      sugar synthesis, but not a typical secretory cargo. While COPII vesicles formed
      in vitro were sedimentable by centrifugation at 200,000g(max) for 15 min, the
      novel vesicles were not. However, they were sedimented by additional
      centrifugation at the same speed for 1 h. Immunoelectron microscopy showed that
      the Dpm1p-containing vesicles had small vesicular/saccular structures of around
      40-50 nm in diameter. The addition of glycerol-3-phosphate and oleoyl-CoA,
      substrates for lipid biosynthesis, significantly enhanced the efficiency of
      vesicle budding in an ATP-dependent fashion. Dpm1p was localized to lipid
      droplets as well as endoplasmic reticulum. Fluorescence microscopy further showed
      that Dpm1p-GFP was present in restricted subregions in isolated lipid droplets.
      The possibility that the vesicles were intermediates from the endoplasmic
      reticulum to lipid droplets was examined, and their possible role is discussed.

PMID- 18343876
TI  - Invited commentary: the hidden population in perinatal epidemiology.
AB  - Several recent papers have argued that understanding of pathologic perinatal
      processes may be advanced by considering, in varying ways, the population of
      fetuses still in utero. Initially invoked by Yudkin et al. (Lancet 1987;1:1192-4)
      as the optimum denominator for intrapartum stillbirths, fetuses in utero (or
      "fetuses at risk") have also been of interest because of their patterns of
      growth, especially in comparison to infants born after varying durations of
      gestation. The paper by Hutcheon and Platt (Am J Epidemiol 2008;167:786-792)
      extends work that compares growth in infants born prematurely with that in
      infants continuing in utero and investigates the biases in analyses that can
      emerge from failure to consider the selection for impaired fetal growth
      characteristic of many prematurely born infants. Although the conceptual basis of
      this perspective is sound, in-utero fetal growth standards from serial
      ultrasonographic measurements in pregnancy are often based on small and highly
      selected samples. Some authors have proposed "fetuses at risk" as the appropriate
      denominator for postnatal phenomena related to premature birth, such as neonatal
      mortality and cerebral palsy. This application is problematic; in such
      situations, the denominator population differs from infants with the outcome in
      not having experienced adjustment to postnatal life, a potentially important
      determinant of outcome, especially in premature infants. The fetuses-at-risk
      concept is important in perinatal epidemiology and has implications for obstetric
      practice, but it must be handled with caution.

PMID- 18343877
TI  - Maternal dietary intake of vitamin A and risk of orofacial clefts: a population
      based case-control study in Norway.
AB  - A population-based case-control study was carried out in Norway between 1996 and
      2001. The aim was to evaluate the association between maternal intake of vitamin
      A from diet and supplements and risk of having a baby with an orofacial cleft.
      Data on maternal dietary intake were available from 535 cases (188 with cleft
      palate only and 347 with cleft lip with or without cleft palate) and 693
      controls. The adjusted odds ratio for isolated cleft palate only was 0.47 (95%
      confidence interval: 0.24, 0.94) when comparing the fourth and first quartiles of
      maternal intake of total vitamin A. In contrast, there was no appreciable
      association of total vitamin A with isolated cleft lip with or without cleft
      palate. An intake of vitamin A above the 95th percentile was associated with a
      lower estimated risk of all isolated clefts compared with the 40th-60th
      percentile (adjusted odds ratio = 0.48, 95% confidence interval: 0.20, 1.14).
      Maternal intake of vitamin A is associated with reduced risk of cleft palate
      only, and there is no evidence of increased risk of clefts among women in our
      study with the highest 5% of vitamin A intake.

PMID- 18343878
TI  - Incident diabetes and pesticide exposure among licensed pesticide applicators:
      Agricultural Health Study, 1993-2003.
AB  - Exposure to certain environmental toxicants may be associated with increased risk
      of developing diabetes. The authors' aim was to investigate the relation between
      lifetime exposure to specific agricultural pesticides and diabetes incidence
      among pesticide applicators. The study included 33,457 licensed applicators,
      predominantly non-Hispanic White males, enrolled in the Agricultural Health
      Study. Incident diabetes was self-reported in a 5-year follow-up interview (1999
      2003), giving 1,176 diabetics and 30,611 nondiabetics for analysis. Lifetime
      exposure to pesticides and covariate information were reported by participants at
      enrollment (1993-1997). Using logistic regression, the authors considered two
      primary measures of pesticide exposure: ever use and cumulative lifetime days of
      use. They found seven specific pesticides (aldrin, chlordane, heptachlor,
      dichlorvos, trichlorfon, alachlor, and cyanazine) for which the odds of diabetes
      incidence increased with both ever use and cumulative days of use. Applicators
      who had used the organochlorine insecticides aldrin, chlordane, and heptachlor
      more than 100 lifetime days had 51%, 63%, and 94% increased odds of diabetes,
      respectively. The observed association of organochlorine and organophosphate
      insecticides with diabetes is consistent with results from previous human and
      animal studies. Long-term exposure from handling certain pesticides, in
      particular, organochlorine and organophosphate insecticides, may be associated
      with increased risk of diabetes.

PMID- 18343879
TI  - Pulmonary function and the risk of functional limitation in chronic obstructive
      pulmonary disease.
AB  - The authors' objective was to analyze the impact of respiratory impairment on the
      risk of physical functional limitations among adults with chronic obstructive
      pulmonary disease (COPD). They hypothesized that greater pulmonary function
      decrement would result in a broad array of physical functional limitations
      involving organ systems remote from the lung, a key step in the pathway leading
      to overall disability. The authors used baseline data from the Function, Living,
      Outcomes, and Work (FLOW) study, a prospective cohort study of adults with COPD
      recruited from northern California in 2005-2007. They studied the impact of
      pulmonary function impairment on the risk of functional limitations using
      validated measures: lower extremity function (Short Physical Performance
      Battery), submaximal exercise performance (6-Minute Walk Test), standing balance
      (Functional Reach Test), skeletal muscle strength (manual muscle testing with
      dynamometry), and self-reported functional limitation (standardized item
      battery). Multiple variable analysis was used to control for confounding by age,
      sex, race, height, educational attainment, and cigarette smoking. Greater
      pulmonary function impairment, as evidenced by lower forced expiratory volume in
      1 second (FEV(1)), was associated with poorer Short Physical Performance Battery
      scores and less distance walked during the 6-Minute Walk Test. Lower forced
      expiratory volume in 1 second was also associated with weaker muscle strength and
      with a greater risk of self-reported functional limitation (p < 0.05). In
      conclusion, pulmonary function impairment is associated with multiple
      manifestations of physical functional limitation among COPD patients.
      Longitudinal follow-up can delineate the impact of these functional limitations
      on the prospective risk of disability, guiding preventive strategies that could
      attenuate the disablement process.

PMID- 18343880
TI  - Dietary boron and hormone replacement therapy as risk factors for lung cancer in
      women.
AB  - Hormone replacement therapy (HRT) may reduce lung cancer risk. Dietary boron may
      have actions similar to those of HRT; however, no previous study has reported the
      associations between dietary boron intake and lung cancer risk or the joint
      effects of boron intake and HRT use on lung cancer risk. The authors examined the
      associations between boron intake and the joint effects of boron intake and HRT
      on lung cancer risk in women. In an ongoing case-control study in Houston, Texas
      (July 1995 through April 2005, end date for this analysis), 763 women were
      diagnosed with lung cancer, and 838 were matched healthy controls with data on
      both diet and HRT. Multiple logistic regression analyses were conducted to assess
      the associations between dietary boron and HRT with lung cancer risk. After
      adjustment for potential confounders, the odds ratios for lung cancer with
      decreasing quartiles of dietary boron intake were 1.0, 1.39 (95% confidence
      interval (CI): 1.02, 1.90), 1.64 (95% CI: 1.20, 2.24), and 1.95 (95% CI: 1.42,
      2.68) mg/day, respectively, for all women (p(trend) < 0.0001). In joint-effects
      analyses, compared with women with high dietary boron intake who used HRT, the
      odds ratio for lung cancer for low dietary boron intake and no HRT use was 2.07
      (95% CI: 1.53, 2.81). Boron intake was inversely associated with lung cancer in
      women, whereas women who consumed low boron and did not use HRT were at
      substantial increased odds.

PMID- 18343881
TI  - Determinants and outcomes of serious attempted suicide: a nationwide study in
      Finland, 1996-2003.
AB  - Suicide is among the 10 leading causes of death. Attempted suicide is 10-40 times
      more frequent than completed suicide and is the strongest single predictor of
      subsequent suicide. The current study population included all persons in Finland
      who were hospitalized with a diagnosis of attempted suicide between 1996 and 2003
      (N = 18,199). Information on background variables and mortality was obtained by
      register linkage. The risk of repeated attempted suicide was 30% and the risk of
      suicide was 10%. The risks of repeated attempted suicide, completed suicide, and
      death from any cause were high immediately after discharge from the hospital.
      Analysis of competing causes of death revealed that while alcohol-related
      disorder was not associated with suicide, it markedly increased the risk of other
      violent death: The subdistribution hazards rate (SHR) was 2.61 (95% confidence
      interval (CI): 2.12, 3.21). Schizophrenia-related disorders (SHR = 1.87, 95% CI:
      1.57, 2.21) and mood disorders (SHR = 1.72, 95% CI: 1.47, 2.01) were associated
      with the risk of suicide. The risks of suicide and all-cause mortality were
      extremely high immediately after hospitalization for attempted suicide.

PMID- 18343882
TI  - The missing data problem in birth weight percentiles and thresholds for "small
      for-gestational-age".
AB  - Weight-for-gestational-age charts and definitions of "small-for-gestational-age"
      based on the distribution of livebirths at a given gestational age have
      conventionally been used to identify infants whose fetal growth is poor. However,
      references based on the weights of only livebirths have serious shortcomings at
      preterm ages due to missing data on the weights of fetuses still in utero, and
      these missing data introduce considerable bias to etiologic studies of fetal
      growth restriction. Application of standard epidemiologic approaches for missing
      data is needed to help produce perinatal weight percentiles that provide unbiased
      assessment of fetal growth and risks of small-for-gestational-age.

PMID- 18343883
TI  - A likelihood-based approach to mixed modeling with ambiguity in cluster
      identifiers.
AB  - This manuscript describes a novel, linear mixed-effects model-fitting technique
      for the setting in which correlated data indicators are not completely observed.
      Mixed modeling is a useful analytical tool for characterizing genotype-phenotype
      associations among multiple potentially informative genetic loci. This approach
      involves grouping individuals into genetic clusters, where individuals in the
      same cluster have similar or identical multilocus genotypes. In haplotype-based
      investigations of unrelated individuals, corresponding cluster assignments are
      unobservable since the alignment of alleles within chromosomal copies is not
      generally observed. We derive an expectation conditional maximization approach to
      estimation in the mixed modeling setting, where cluster assignments are
      ambiguous. The approach has broad relevance to the analysis of data with missing
      correlated data identifiers. An example is provided based on data arising from a
      cohort of human immunodeficiency virus type-1-infected individuals at risk for
      antiretroviral therapy-associated dyslipidemia.

PMID- 18343884
TI  - DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta
      analysis.
AB  - Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the
      ability of the individual to metabolically activate carcinogens and to repair DNA
      damage. Their ability to predict cancer onset is uncertain. We have performed a
      pooled analysis of three prospective studies on cancer risk in which bulky DNA
      adducts have been measured in blood samples collected from healthy subjects (N =
      1947; average follow-up 51-137 months). In addition, we have performed a meta
      analysis by identifying all articles on the same subject published up to the end
      of 2006, including case-control studies. In the pooled analysis, a weakly
      statistically significant increase in the risk of lung cancer was apparent (14%
      per unit standard deviation change in adduct levels, 95% confidence interval 1
      28%; using the weighted mean difference method, 0.15 SD, units higher adducts in
      cases than in controls). The association was evident only in current smokers and
      was absent in former smokers. Also the meta-analysis, which included both lung
      and bladder cancers, showed a statistically significant association in current
      smokers, whereas the results in never smokers were equivocal; in former smokers,
      no association was detected. The results of our pooled and meta-analyses suggest
      that bulky DNA adducts are associated with lung cancer arising in current smokers
      after a follow-up of several years.

PMID- 18343885
TI  - Variability in the secretion of corticotropin-releasing hormone,
      adrenocorticotropic hormone and cortisol and understandability of the
      hypothalamic-pituitary-adrenal axis dynamics--a mathematical study based on
      clinical evidence.
AB  - In this article, we have developed a simple mathematical model that captures the
      vital mechanisms of the hypothalamic-pituitary-adrenal (HPA) axis self-regulatory
      activities. For this, a system of three-component non-linear delay differential
      equations has been proposed and analysed to observe the ultradian and circadian
      variabilities of the hormone secretion of the HPA axis in normal subjects. Our
      analysis reveals that a feedback mechanism is sufficient to show the ultradian
      variability of the hormone secretion pattern but fails to show the circadian
      variability. A central nervous system-driven pulse generator coupled with the
      primary feedback mechanism can exhibit the ultradian as well as circadian
      variability in the hormone secretion of the HPA axis. The model can also predict
      different dynamics of the normal HPA axis following physiological changes (viz.
      adrenalectomy and hypophysectomy) and pathological changes (viz. infusion of
      different hormones).

PMID- 18343886
TI  - Shortening of cardiac action potential duration near an insulating boundary.
AB  - It is known, from both experiments and simulations, that cardiac action
      potentials are shortened near a non-conducting boundary. In the present paper,
      this effect is studied in a simple, two-current ionic model, with propagation
      restricted to a 1D fibre. An asymptotic approximation for the dependence of
      action potential duration on distance to the boundary is derived. This estimate
      agrees well with simulations.

PMID- 18343887
TI  - Regulation of carotenoid biosynthetic genes expression and carotenoid
      accumulation in the green alga Haematococcus pluvialis under nutrient stress
      conditions.
AB  - Haematococcus pluvialis, a green alga, accumulates carotenoids, predominantly
      astaxanthin, when exposed to stress conditions. In the present work, changes in
      the pigment profile and expression of carotenogenic genes under various nutrient
      stress conditions and their regulation were studied. Nutrient stress and higher
      light intensity in combination with NaCl/sodium acetate (SA) enhanced total
      carotenoid and total astaxanthin content to 32.0 and 24.5 mg g(-1) of dry
      biomass, respectively. Expression of carotenogenic genes, phytoene synthase
      (PSY), phytoene desaturase (PDS), lycopene cyclase (LCY), beta-carotene ketolase
      (BKT), and beta-carotene hydroxylase (CHY) were up-regulated under all the stress
      conditions studied. However, the extent of expression of carotenogenic genes
      varied with stress conditions. Nutrient stress and high light intensity induced
      expression of astaxanthin biosynthetic genes, BKT and CHY, transiently. Enhanced
      expression of these genes was observed with SA and NaCl/SA, while expression was
      delayed with NaCl. The maximum content of astaxanthin recorded in cells grown in
      medium with SA and NaCl/SA correlated with the expression profile of the
      astaxanthin biosynthetic genes. Studies using various inhibitors indicated that
      general carotenogenesis and secondary carotenoid induction were regulated at both
      the transcriptional and the cytoplasmic translational levels. The induction of
      general carotenoid synthesis genes was independent of cytoplasmic protein
      synthesis while BKT gene expression was dependent on de novo protein synthesis.

PMID- 18343888
TI  - Elicitor-dependent expression of the ribosome-inactivating protein beetin is
      developmentally regulated.
AB  - BE27 and BE29 are two forms of beetin, a virus-inducible type 1 ribosome
      inactivating protein isolated from leaves of Beta vulgaris L. Western blot
      analysis revealed the presence of beetin forms in adult plants but not in germ or
      young plants, indicating that the expression of these proteins is developmentally
      regulated. While beetins are expressed only in adult plants, their transcripts
      are present through all stages of development. In addition, the treatment of B.
      vulgaris leaves with mediators of plant-acquired resistance such as salicylic
      acid and hydrogen peroxide promoted the expression of beetin by induction of its
      transcript, but only in adult plants. The plant expresses three mRNAs which
      differ only in their 3' untranslated region. All these observations suggest a
      dual regulation of beetin expression, i.e. at the post-transcriptional and
      transcriptional levels. Additionally, total RNA isolated from leaves treated with
      hydrogen peroxide, which express high levels of active beetin, is not de
      adenylated by endogenous beetin, nor in vitro by the addition of BE27, thus
      suggesting that sugar beet ribosomes are resistant to beetin.

PMID- 18343889
TI  - Gr1+IL-4-producing innate cells are induced in response to Th2 stimuli and
      suppress Th1-dependent antibody responses.
AB  - Alum is used as a vaccine adjuvant and induces T(h)2 responses and T(h)2-driven
      antibody isotype production against co-injected antigens. Alum also promotes the
      appearance in the spleen of Gr1+IL-4+ innate cells that, via IL-4 production,
      induce MHC II-mediated signaling in B cells. To investigate whether these Gr1+
      cells accumulate in the spleen in response to other T(h)2-inducing stimuli and to
      understand some of their functions, the effects of injection of alum and eggs
      from the helminth, Schistosoma mansoni, were compared. Like alum, schistosome
      eggs induced the appearance of Gr1+IL-4+ cells in spleen and promoted MHC II
      mediated signaling in B cells. Unlike alum, however, schistosome eggs did not
      promote CD4 T cell responses against co-injected antigens, suggesting that the
      effects of alum or schistosome eggs on splenic B cells cannot by themselves
      explain the T cell adjuvant properties of alum. Accordingly, depletion of IL-4 or
      Gr1+ cells in alum-injected mice had no effect on the ability of alum to improve
      expansion of primary CD4 T cells. However, Gr1+ cells and IL-4 played some role
      in the effects of alum, since depletion of either resulted in antibody responses
      to antigen that included not only the normal T(h)2-driven isotypes, like IgG1,
      but also a T(h)1-driven isotype, IgG2c. These data suggest that alum affects the
      immune response in at least two ways: one, independent of Gr1+ cells and IL-4,
      that promotes CD4 T cell proliferation and another, via Gr1+IL-4+ cells, that
      participates in the polarization of the response.

PMID- 18343890
TI  - Modulation of T cell homeostasis and alloreactivity under continuous FTY720
      exposure.
AB  - The immunomodulator FTY720 inhibits lymph node (LN) and thymic egress, thereby
      constraining T cell circulation and reducing peripheral T cell numbers. Here, we
      analyzed in mouse models the as yet scarcely characterized impact of long-term
      (up to 6 months) FTY720 exposure on T cell homeostasis and possible consequences
      for alloreactivity. In green fluorescent protein (GFP) hemopoietic chimeras, the
      turnover of (initially GFP(-)) peripheral T cell pools was markedly delayed under
      FTY720, while normal homeostatic differences between CD4 and CD8 T cell sub
      populations were retained or amplified further. Homeostatic proliferation was
      enhanced, and within shrinking T cell pools, the proportions of effector memory
      phenotype CD4 T cells (CD4T(PEM)) increased in spleens and LNs and of central
      memory phenotype CD8 T cells (CD8T(PCM)) in LNs. By contrast, the fractions of
      CD8T(PEM) and CD4T(PCM) remained stably small under FTY720. The enrichment for
      CD4T(PEM) and CD8T(PCM) correlated with larger proportions of IFNgamma-producing
      T cells upon nonspecific but not allospecific stimulation. Splenic CD4 T cells
      from FTY720-treated mice proliferated more strongly upon transfer to semi
      allogeneic hosts. However, heart allograft survival was not compromised in FTY720
      pre-treated recipients. It correlated with reduced intra-graft CD8 T cells, and
      the longest surviving transplants contained the highest numbers of CD4 T cells.
      Thus, continuous FTY720 exposure reveals differential homeostatic responses by
      memory phenotype CD4 and CD8 T cell sub-populations, and it may enhance
      alloreactive CD4 T cell proliferation and tissue infiltration without
      accelerating allograft rejection.

PMID- 18343891
TI  - Mobility pathways for vertebrate L1, L2, CR1, and RTE clade retrotransposons.
AB  - Autonomous non-long terminal repeat retrotransposons (NLRs) are ubiquitous mobile
      genetic elements that insert their DNA copies at new locations by
      retrotransposition. In vertebrates, there are 4 NLR clades, L1, L2, CR1, and RTE,
      which diverged in the Precambrian era. It has been demonstrated that
      retrotransposition of L1 and L2 members proceeds via coordinated reactions of
      targeted DNA cleavage and reverse transcription catalyzed by the NLR-encoded
      proteins, which are followed by the joining of the 5' (upstream) junction.
      However, the study on the mobility pathways for vertebrate NLRs is so far limited
      to L1 and L2. In this report, using target analysis of nested transposons for
      genomic copies, we studied retrotransposition pathways for a variety of
      vertebrate NLRs, including those of the L1, L2, CR1, and RTE clades in the human,
      cow, opossum, chicken, and zebrafish genomes. Thus, this study constitutes the
      first comprehensive analysis of NLR retrotransposition products in vertebrates.
      Our data revealed that these elements share similar mechanisms for the cleavages
      of the 2 target DNA strands and for the initiation of reverse transcription.
      Possible endonuclease-independent insertions were also identified. Overall, our
      results suggest the existence of multiple retrotransposition pathways that are
      conserved among the diverse NLR clades in various vertebrate hosts.

PMID- 18343892
TI  - On the expansion of the pentatricopeptide repeat gene family in plants.
AB  - Pentatricopeptide repeat (PPR) proteins form a huge family in plants (450 members
      in Arabidopsis and 477 in rice) defined by tandem repetitions of characteristic
      sequence motifs. Some of these proteins have been shown to play a role in
      posttranscriptional processes within organelles, and they are thought to be
      sequence-specific RNA-binding proteins. The origins of this family are obscure as
      they are lacking from almost all prokaryotes, and the spectacular expansion of
      the family in land plants is equally enigmatic. In this study, we investigate the
      growth of the family in plants by undertaking a genome-wide identification and
      comparison of the PPR genes of 3 organisms: the flowering plants Arabidopsis
      thaliana and Oryza sativa and the moss Physcomitrella patens. A large majority of
      the PPR genes in each of the flowering plants are intron less. In contrast, most
      of the 103 PPR genes in Physcomitrella are intron rich. A phylogenetic comparison
      of the PPR genes in all 3 species shows similarities between the intron-rich PPR
      genes in Physcomitrella and the few intron-rich PPR genes in higher plants.
      Intron-poor PPR genes in all 3 species also display a bias toward a position of
      their introns at their 5' ends. These results provide compelling evidence that
      one or more waves of retrotransposition were responsible for the expansion of the
      PPR gene family in flowering plants. The differing numbers of PPR proteins are
      highly correlated with differences in organellar RNA editing between the 3
      species.

PMID- 18343893
TI  - Comparative temporal toxicogenomic analysis of TCDD- and TCDF-mediated hepatic
      effects in immature female C57BL/6 mice.
AB  - Temporal analyses were performed on hepatic tissue from immature female C57BL/6
      mice in order to compare the gene expression profiles for 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) and 2,3,7,8-tetrachlorodibzofuran (TCDF). Time
      course studies conducted with a single oral dose of 300 microg/kg TCDF or 30
      microg/kg TCDD were used to compare differential gene expression on complementary
      DNA microarrays containing 13,361 features, representing 8194 genes at 2, 4, 8,
      12, 24, 72, 120, and 168 h. One hundred and ninety-five genes were identified as
      differentially regulated by TCDF, of which 116 genes were in common with TCDD,
      with 109 exhibiting comparable expression profiles (correlation coefficients >
      0.3). In general, TCDF was less effective in eliciting hepatic vacuolization, and
      differential gene expression compared with TCDD when given at an equipotent dose
      based on a toxic equivalence factor (TEF) of 0.1 for TCDF, especially 72-h
      postadministration. For example, the induction of Cyp1a1 messenger RNA by TCDF
      was less when compared TCDD. Moreover, TCDF induced less severe hepatocyte
      cytoplasmic vacuolization consistent with lower lipid accumulations which
      significantly subsided by 120 and 168 h when compared with TCDD. TCDF-elicited
      responses correlated with their hepatic tissue levels which gradually decreased
      between 18 and 168 h. Although both compounds elicited comparable gene expression
      profiles, especially at early time points, the TCDF responses were generally
      weaker. Collectively, these results suggest that the weaker TCDF responses could
      be attributed to differences in pharmacokinetics. However, more comprehensive
      dose-response studies are required at optimal times for each end point of
      interest in order to investigate the effect of pharmacokinetic differences on
      relative potencies that are important in establishing TEFs.

PMID- 18343894
TI  - Does the degree of advancement during functional appliance therapy matter?
AB  - The aim of this study was to assess the effect of varied degrees of mandibular
      advancement on condylar growth. Three hundred and thirty five 35-day-old female
      Sprague-Dawley rats were randomly divided into 10 experimental groups (n = 10)
      and five control groups (n = 5) for analysis of new bone formation and 10
      experimental groups (n = 14) and five control groups (n = 14) for molecular
      analysis. The experimental animals were fitted with bite-jumping appliance to
      advance the mandible 2 and 4 mm. The rats were sacrificed on days 3, 7, 14, 21,
      and 30. A computer-assisted image analysing system was used to assess the
      quantity of new condylar bone formation. Molecular analysis utilizing real-time
      reverse transcription-polymerase chain reaction was used to assess the different
      levels of mRNA expression of different growth markers in the condyle. One-way
      analysis of variance (ANOVA), with a Bonferroni multiple comparison test, showed
      significantly more newly formed bone in the 4 mm group compared with the 2 mm and
      control groups on days 21 and 30 (P < 0.05). Most of the examined growth markers
      demonstrated a significant increase during the 4 mm advancement (P < 0.05).
      Indian hedgehog (Ihh) mRNA showed a 7- and 5-fold change, parathyroid hormone
      related peptide (PTHrP) a 5.2- and 3-fold change and type II collagen a 9.6- and
      3.7-fold change in the 4 and 2 mm advancement groups, respectively. Varied
      degrees of mandibular advancement result in different quantities of new bone
      formation and levels of expression of growth members: Ihh, PTHrP, and type II
      collagen.

PMID- 18343895
TI  - Nucleotide diversity and linkage disequilibrium in wild avocado (Persea americana
      Mill.).
AB  - Resequencing studies provide the ultimate resolution of genetic diversity because
      they identify all mutations in a gene that are present within the sampled
      individuals. We report a resequencing study of Persea americana, a subtropical
      tree species native to Meso- and Central America and the progenitor of cultivated
      avocado. The sample includes 21 wild accessions from Mexico, Costa Rica, Ecuador,
      and the Dominican Republic. Estimated levels of nucleotide polymorphism and
      linkage disequilibrium (LD) are obtained from fully resolved haplotype data from
      4 nuclear loci that span 5960 nucleotide sites. Results show that, although
      avocado is a subtropical tree crop and a predominantly outcrossing plant, the
      overall level of genetic variation is not exceptionally high (nucleotide
      diversity at silent sites, pi(sil) = 0.0102) compared with available estimates
      from temperate plant species. Intralocus LD decays rapidly to half the initial
      value within about 1 kb. Estimates of recombination rate (based on the sequence
      data) show that the rate is not exceptionally high when compared with annual
      plants such as wild barley or maize. Interlocus LD is significant owing to
      substantial population structure induced by mixing of the 3 botanical races of
      avocado.

PMID- 18343896
TI  - Role of diet and fuel overabundance in the development and progression of heart
      failure.
AB  - Under physiological conditions, the human heart derives energy from glucose,
      fatty acids, and/or lactate depending upon substrate availability, circulating
      hormone levels, and nutritional status. Circulating free fatty acid and glucose
      levels often exceed the normal range, as observed with type 2 diabetes, obesity,
      or physical inactivity. Chronic exposure of the heart to high plasma levels of
      free fatty acids may cause accumulation of toxic lipid intermediates within
      cardiomyocytes. Furthermore, suppression of glucose oxidation by increased fatty
      acid uptake shunts glucose into the oxidative pentose phosphate and hexosamine
      biosynthetic pathways, both of which yield potentially harmful products. Noxious
      derivatives of aberrant glucose and fatty acid oxidation can activate signalling
      cascades leading to myocyte dysfunction or death, processes termed
      'glucotoxicity' and 'lipotoxicity'. This review discusses the effects of dietary
      extremes (e.g. high fat and high carbohydrate consumption) and substrate
      overabundance in the context of heart failure (HF) development and progression.
      Emerging data suggest that substrate excess leads to cardiac dysfunction and HF,
      which may be prevented or slowed by maintaining low body fat and high insulin
      sensitivity and consuming a diet of low glycaemic load that is high in mono- and
      polyunsaturated fatty acids.

PMID- 18343897
TI  - Depletion of zebrafish essential and regulatory myosin light chains reduces
      cardiac function through distinct mechanisms.
AB  - AIMS: Mutations in the essential myosin light chain (ELC) and regulatory myosin
      light chain (RLC) genes have been linked to sarcomeric hypertrophic
      cardiomyopathies in humans; however, the specific functions of the different
      myosin light chains during cardiogenesis in a vertebrate animal are not well
      understood. METHODS AND RESULTS: Using zebrafish (Danio rerio) as a model
      organism, we have identified cmlc1 and cmlc2 as the main ELC and RLC orthologues,
      respectively, and have furthermore characterized their functions during
      cardiogenesis by morpholino technology. Depletion of either cmlc1 or cmlc2 using
      morpholino-modified antisense oligonucleotides leads to a disruption in sarcomere
      structure and compromises cardiac function as well, although through seemingly
      distinct mechanisms. While myosin still assembles into a novel rod-like structure
      in both morphants, the sarcomere length is longer in cmlc1 morphants than that in
      wild-type embryos, whereas it is shorter in cmlc2 morphants. In addition,
      cardiomyocyte size and number are increased upon depletion of cmlc1, resulting in
      a larger ventricular chamber volume; in contrast, depletion of cmlc2 leads to a
      reduction in cardiomyocyte size and number. CONCLUSION: Our data have elucidated
      distinct roles for cmlc1 and cmlc2 during zebrafish cardiogenesis, suggesting
      that cardiomyopathies resulting from human mutations in ELCs vs. RLCs may have
      distinct pathological characteristics during disease progression.

PMID- 18343899
TI  - Advances in assays of matrix metalloproteinases (MMPs) and their inhibitors.
AB  - Matrix metalloproteinases (MMPs) play an important role in many physiological and
      pathological processes. To assay the activities of MMPs is important in diagnosis
      and therapy of the MMPs associated diseases, such as neoplastic, rheumatic and
      cardiovascular diseases. Several assay systems have been developed, which include
      bioassay, zymography assay, immunoassay, fluorimetric assay, radio isotopic
      assay, phage-displayed assay, multiple-enzyme/multiple-reagent assay and activity
      based profiling assay. The principle, application, advantage and disadvantage of
      these assays have been reviewed in this article.

PMID- 18343900
TI  - A quantitative structure-activity relationship study of novel, potent, orally
      active, selective VEGFR-2 and PDGFRalpha tyrosine kinase inhibitors: derivatives
      of N-phenyl-N'-{4-(4-quinolyloxy)phenyl}urea as antitumor agents.
AB  - The tyrosine kinase inhibitory action of the derivatives of N-Phenyl-N'-{4-(4
      quinolyloxy)phenyl}urea is quantitatively analyzed using multiple regression
      analysis. The analysis has helped to ascertain the role of different substituents
      in explaining the observed inhibitory actions of these compounds for two
      receptors, namely vascular endothelial growth factor receptor 2 (VEGFR-2) and
      platelet-derived growth factor receptor alpha (PDGFRalpha). From a derived
      significant correlation equation for inhibition of VEGFR-2, it was concluded that
      a less hydrophobic molecule with ortho-substituent(s), exerting less steric
      hindrance and para-substituent devoid of hydrogen-bond acceptor property augment
      the inhibition action. Besides, a 3-substituent transmitting a higher negative
      field effect is advantageous to improve the pIC(50) value of a compound. The
      correlation equation, derived for the inhibition of PDGFRalpha, has revealed that
      a less hydrophobic molecule, having a 3-substituent which transmits a more
      negative resonance effect, is helpful in raising its activity. Likewise, in the
      middle phenyl ring, absence of a fluoro substituent augments the inhibitory
      activity. Based on derived QSAR equations pertaining to VEGF-2 and PDGFalpha
      receptors, the drawn guidelines for selection of substituents, may be used to
      synthesize potent compounds in future.

PMID- 18343901
TI  - Functional characterization and specific effects of various peptides on enzymatic
      activity of a DPP-III homologue from goat brain.
AB  - The purified dipeptidyl aminopeptidase from goat brain showed several
      characteristics similar to DPP-III although it possesses a dissimilar molecular
      weight and different inhibition behavior. The enzyme was found to be inhibited by
      metallochelators and thiol inhibitors which could be reversed by introducing
      metals and thiols, respectively. The enzyme activity is also significantly
      affected by DMSO and ethanol. It was found to be highly sensitive to even very
      low concentration of urea. The inhibitory potency of several dipeptides and
      bioactive peptides on this enzyme was investigated to characterize its active
      site. The highest potency was observed for the dipeptides having aromatic and
      bulky side chains such as Phe-Met, Leu-Arg, Met-Arg, Trp-Met and Leu-Trp.

PMID- 18343902
TI  - A study on the inhibition of adenosine deaminase.
AB  - Adenosine deaminase (ADA, EC 3.5.4.4) catalyses the irreversible deamination of
      adenosine and 2'-deoxyadenosine to inosine and 2'-deoxyinosine, respectively. In
      this study the inhibition of ADA from bovine spleen by several molecules with
      structure related to that of the substrate or product has been quantified. The
      inhibitors adenine, purine, inosine, 2-aminopurine, 4-aminopyrimidine, 4
      aminopyridine, 4-hydroxypyridine and phenylhydrazine are shown to be competitive
      inhibitors with K(I) (mM) values of 0.17, 1.1, 0.35, 0.33, 1.3, 1.8, 1.4 and
      0.25, respectively. Synergistic inhibition by various combinations of molecules
      that imitate the structure of the substrate has never been observed. Some general
      conclusions are: i) the enzyme ADA from bovine spleen we have used is appropriate
      for kinetic studies of inhibition and mechanistic studies; it can be a reference
      catalytic system for the homogeneous comparison of various inhibitors; ii) this
      enzyme presents very rigid requirements for binding the substrate: variations in
      the structure of adenosine imply the loss of important interactions.

PMID- 18343903
TI  - Peptidomimetic 2-cyanopyrrolidines as potent selective cathepsin L inhibitors.
AB  - Cathepsins have been found to have important physiological roles. The implication
      of cathepsin L in various types of cancers is well established. In a search for
      selective cathepsin L inhibitors as anticancer agents, a series of 2
      cyanoprrolidine peptidomimetics, carrying a nitrile group as warhead, were
      designed. Two series of compounds, one with a benzyl moiety and a second with an
      isobutyl moiety at P(2) position of the enzyme were synthesized. The synthesized
      compounds were evaluated for inhibitory activity against human cathepsin L and
      cathepsin B. Although, none of the compounds showed promising inhibitory
      activity, (E)N-{(S)1-[(S)2-cyano-1-pyrrolidinecarbonyl]-3-methylbutyl}-2,3
      diphenylacrylamide (24) with an isobutyl moiety at P(2) was found to show
      selectivity as a cathepsin L inhibitor (Ki 5.3 microM for cathepsin L and Ki >
      100 microM for cathepsin B). This compound could act as a new lead for the
      further development of improved inhibitors within this inhibitor type.

PMID- 18343904
TI  - Evaluation of a novel aminopeptidase N inhibitor, in vitro, using two assay
      systems.
AB  - The activities of the novel aminopeptidase N inhibitor (APNI), beta-Amino-alpha
      Hydroxyl-Phenyl butanic acid-Valine (AHPA-Val), were compared with APNI
      (amastatin). AHPA-Val and amastatin produced competitive inhibition of the
      hydrolysis of Tyr-Gly in the guinea-pig striatal membrane preparation, with K(i)
      equal to 14.06 microM and 12.48 microM respectively. Met-enkephalin-induced
      twitch inhibition of the guinea-pig ileum preparation was enhanced by AHPA-Val
      and amastatin with pA(1/2) values (the negative logarithm concentration of APNI
      that decreased the IC(50) of Met-enkephalin by half), of 7.08 and 7.79
      respectively. These results suggest that AHPA-Val has good activity as an APNI
      and that these two assay systems are useful for evaluating the potency of novel
      APNIs.

PMID- 18343905
TI  - Structural insight into the inhibition of acetylcholinesterase by 2,3,4, 5
      tetrahydro-1, 5-benzothiazepines.
AB  - Benzothiazepines 1-3 inhibited acetylcholinesterase (AChE; EC 3.1.1.7) enzyme in
      a concentration-dependent fashion with IC(50) values of 1.0 +/- 0.002, 1.2 +/-
      0.005 and 1.3 +/- 0.001 microM, respectively. By using linear-regression
      equations, Lineweaver-Burk, Dixon plots and their secondary replots were
      constructed which indicated that compounds 1-3 are non-competitive inhibitors of
      AChE with K(i) values of 0.8 +/- 0.04, 1.1 +/- 0.002, and 1.5 +/- 0.001 microM,
      respectively. Molecular docking studies revealed that all the compounds are
      completely buried inside the aromatic gorge of AChE, extending deep into the
      gorge of AChE. A comparison of the docking results of compounds 1-3 displayed
      that these compounds generally adopt the same binding mode in the active site of
      AChE. The superposition of the docked structures demonstrated that the non
      flexible benzothiazepine always penetrate into the aromatic gorge through the six
      membered ring A, which allowed the ligands to interact simultaneously with more
      than one subsites of the active center of AChE. The higher AChE inhibitory
      potential of compounds 1-3 was found to be the cumulative effect of hydrophobic
      contacts and pi-pi interactions between the ligands and AChE. The relatively high
      affinity of benzothiazepine 1 with AChE was found to be due to additional
      hydrogen bond in benzothiazepine 1-AChE complex. The results indicated that
      substitution of halogen and methyl groups by hydrogen at aromatic ring of the
      benzothiazepine decreased the affinity of these molecules towards enzyme that may
      be due to the polar non-polar repulsions of these moieties with the amino acid
      residues in the active site of AChE. The observed binding modes of
      benzothiazepines 1-3 in the active site of AChE explain the affinities of
      benzothiazepines and provide a rational basis for the structure-based drug design
      of benzothiazepines with improved pharmacological properties.

PMID- 18343906
TI  - Synthesis, lipophilicity study and in vitro evaluation of some rodenticides as
      acetylcholinesterase reversible inhibitors.
AB  - The anti-AChE activity of phosphoramidates has been noticed for many years.
      Because of the wide application of phosphoramidates in recent years, there has
      been a continuing research for synthesis, purification and identification of
      effective and safe derivatives. In this study some rodenticides with the general
      formula Me(2)NP(O)(p-OC(6)H(4)-X)(2), where X = H, CH(3), Cl, have been
      synthesized in water (without organic solvent) and characterized by (31)P, (31)P
      {(1)H}, (13)C and (1)H NMR spectroscopy. Since lipophilicity has been recognized
      for its importance in QSAR studies, efforts have been made to determine the logP
      values. The ability of these rodenticides to inhibit human acetylcholinesterase
      (hAChE) has been predicted with PASS (Prediction of Activity Spectra for
      Substances) software (version 1.917) and then has been evaluated by a modified
      Ellman's assay and spectrophotometric measurements.

PMID- 18343907
TI  - Evaluation of natural antioxidants of Leuzea carthamoides as a result of a
      screening study of 88 plant extracts from the European Asteraceae and
      Cichoriaceae.
AB  - In recently, there has been a great interest in natural antioxidants as bioactive
      components of food, nutraceuticals or potential drugs against several diseases.
      In our study, 88 extracts from various parts of plants from European Asteraceae
      and Cichoriaceae were assayed for radical scavenging activity by means of DPPH
      (1,1-diphenyl-2-picryl hydrazyl radical) test using the SIA (Sequential injection
      analysis) method developed for this purpose in our laboratory. DPPH radical
      scavenging activity of all tested plant extracts was evaluated according to the
      IC(50) parameter. 29 extracts exhibited IC(50) value lower than 0.1 mg/mL. The
      leaves of Leuzea carthamoides (IC(50) = 0.046 mg/mL) were chosen as the most
      promising sample for a subsequent phytochemical study, which resulted in
      isolation of seven natural compounds, namely, 4',5,7-trihydroxy-6-methoxyflavone
      (hispidulin) (1), 5, 7, 3', 4'- tetrahydroxyflavanone (eriodictyol) (2),
      3',4',5,7-pentahydroxy-6-methoxyflavonol (patuletin) (3), eriodictyol-7-beta
      glucopyranoside (4), 6-hydroxykaempferol-7-O-(6''-O-acetyl-beta-D
      glucopyranoside) (5), 4-hydroxybenzoic acid (6) and 3,4-dihydroxybenzoic acid
      (protocatechuic acid) (7). Antioxidant activity of the isolated compounds was
      evaluated by DPPH test and ferric reducing antioxidant power (FRAP) test and
      compared with trolox and quercetin. Both tests evaluated the flavonoid (5) as the
      most active antioxidant. This result was confirmed by comparison with known data
      concerning the structure/activity relationships of flavonoids.

PMID- 18343908
TI  - Screening and evaluation of antioxidant activity of some pyridazine derivatives.
AB  - Antioxidants are compounds that can delay, inhibit, or prevent the oxidation of
      materials that can be oxidized by scavenging free radicals and help in
      diminishing oxidative stress. They belong to different chemical classes. Recently
      there are studies related to pyridazinone derivatives for their antioxidant
      activities. Since there are evidences implicates reactive oxygen species and
      nitric oxide as mediators of inflammation and/or tissue damage in inflammatory
      and arthritic disorders it was though that compounds that have both antioxidant
      and anti-inflammatory activities would have been essential for the inflammatory
      diseases. Based on these findings a series of 2H-pyridazine-3-one and 6
      chloropyridazine analogues that have anti-inflammatory activity was tested in
      vitro on superoxide formation and effects on lipid peroxidation were determined
      against alpha-tocopherol. Most of the compounds have strong inhibitory effect on
      superoxide anion (between 84% - 99%) at 10(- 3) M concentration. In addition,
      these compounds showed similar activity to alpha-tocopherol at 10(- 3) M
      concentrations.

PMID- 18343909
TI  - Iron(III) complexes: preparation, characterization, antibacterial activity and
      DNA-binding.
AB  - Iron(III) have been combined to well known quinolones (ciprofloxacin) and some
      Schiff bases with the help of coordination approach. Characterization of these
      compounds have been done using elemental analysis, magnetic measurements,
      thermogravimetric analysis, IR, UV-VIS, (1)H NMR and (13)C NMR spectral
      investigation. Analytical studies suggest that the iron(III)-quinolone complexes
      assume a six-coordinated dimeric distorted octahedral geometry. All the compounds
      show a good antibacterial activity against broad range of bacteria like Bacillus
      cereus, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella
      typhi and Serratia marcescens, whereas no significant inhibition towards growth
      of fungal strains like Aspergillus Niger, Aspergillus flavus and Lasiodiplodia
      theobromae. Analyses of all these compounds show effective sperm herring DNA
      inhibition.

PMID- 18343910
TI  - Structure and biological properties of first row d-transition metal complexes
      with N-substituted sulfonamides.
AB  - Cobalt (II), copper (II), nickel (II) and zinc (II) complexes with 2-hydroxy-1
      naphthaldehyde derived N-substituted sulfonamides have been synthesized and the
      nature of bonding and structure of compounds have been deduced from physical,
      analytical and spectral (IR, (1)H NMR, (13)C NMR, Mass and electronic) data. An
      octahedral geometry has been suggested for the complexes. Complexes along with
      the ligands were assessed for their antibacterial and antifungal activities on
      different species of pathogenic bacteria and fungi. The results revealed the
      ligands to possess moderate to significant antibacterial activity which was, in
      many cases, enhanced on chelation. Similar results were observed for antifungal
      activity. Brine shrimp bioassay was also carried out for in vitro cytotoxic
      properties against Artemia salina.

PMID- 18343911
TI  - Effects of radix polygoni multiflori components on tyrosinase activity and
      melanogenesis.
AB  - Radix Polygoni multiflori is a herb used effectively to prevent graying and treat
      skin depigmentation diseases in traditional Chinese medicine but its active
      ingredients have not been discovered yet. In this investigation, we tested six
      compounds isolated from Radix Polygoni multiflori, to discover the active
      component on melanogenesis. Three experiments were performed in the present
      investigation: mushroom tyrosinase activity, melanin content B16 cell
      proliferation assay. Among all the six components tested, THSG showed the most
      potent effects on tyrosinase activation and melanogenesis; it was shown to be a
      potent tyrosinase activator and a melanogenesis stimulator in this study. On the
      other hand, we found that gallic acid significantly inhibited tyrosinase and, in
      addition, anthraquinones were cytotoxic to melanoma cells. They were both harmful
      to melanogenesis. Therefore, we propose that THSG acts as the active ingredient
      of Radix Polygoni multiflori on melanogenesis.

PMID- 18343912
TI  - Antifungal and antibacterial activities of Taxus wallichiana Zucc.
AB  - Current study was undertaken to evaluate the in vitro antifungal and
      antibacterial potential of methanol extract and subsequent fractions obtained
      after partitioning in organic solvents with variable polarity of the aerial parts
      of the tree Taxus wallichiana Zucc. Traditionally, this plant is often used in
      folk medicines in Pakistan for treating microbial infections. In order to
      rationalize the traditional use, methanol extracts of leaf, bark, and heartwood
      of Taxus wallichiana Zucc. were tested against six bacteria and six fungal
      strains using the Hole diffusion and macro-dilution methods. All extracts and
      fractions displayed significant antimicrobial effect. Only three fungal strains,
      Trichophyton longifusus, Microspoum canis, and Fusarium solani were susceptible
      to the extracts and fractions with MICs ranging from 0.08 to 200 mg/mL. In case
      of bacterial strains, Staphylococcus aureus, Pseudomonas aeruginosa and
      Salmonella typhi were susceptible to the extracts and fractions with MICs ranging
      from 0.08 to 200 mg/mL. Comparison results were carried out using imipinem,
      miconazole and amphotericin B as standard antibiotics.

PMID- 18343913
TI  - Effects of nicotine and vitamin E on 6-phosphogluconate dehydrogenase activity in
      some rat tissues in vivo and in vitro.
AB  - The aim of this study was to investigate whether nicotine affects 6
      phosphogluconate dehydrogenase (6PGD) enzyme activity in some rat tissues, and to
      see the modulatory effects of vitamin E on this effect in vivo. In addition, the
      effects of nicotine and vitamin E on 6PGD activity were also tested in vitro. The
      groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine + vitamin
      E [75 mg/kg/day, intragastric (i.g.)]; and control group (receiving only
      vehicles). There were eight rats per group and supplementation period was 3
      weeks. The results of in vivo study showed that nicotine activated the muscle,
      lungs, and testicular 6PGD enzyme activity but had no effect on heart and liver
      6PGD activity. Also, nicotine + vitamin E activated the muscle, testicle, and
      liver 6PGD enzyme activity, while this combination had no effect on heart, and
      lungs in vivo. When nicotine is administered with vitamin E the increase in 6PGD
      enzyme activity in muscle and testicles were lower. On the other hand the
      increase in 6PGD enzyme activity was eliminated by vitamin E in lungs, while 6PGD
      enzyme activity was increased by vitamin E, which was not affected by nicotine
      only. In vitro results correlated well with in vivo experimental results. Our
      results suggest that vitamin E may favourably increase 6PGD enzyme activity in
      liver in nicotine treated rats, while it has negligible effects on this enzyme
      activity in other tissues.

PMID- 18343914
TI  - The effect of ethanol on erythrocyte carbonic anhydrase isoenzymes activity: an
      in vitro and in vivo study.
AB  - The ethanol is a widely consumed as sedative-hypnotic drug throughout the world.
      In this study, the effects of ethanol were investigated on carbonic anhydrase
      (CA) enzyme activities both in vitro in human erythrocyte and in vivo in Sprague
      Dawley rat erythrocyte. For in vitro study, the human carbonic anhydrase-I (HCA
      I) and -II (HCA-II) are purified by Sepharose 4B-L-tyrosine-sulphanilamide
      affinity chromatography. In vivo CA enzyme activity was determined
      colorimetrically by using CO(2)-hydration method of Wilbur and Anderson. Rat
      blood samples were taken from each rat before and after the ethanol
      administration at different times (1 h, 3 h, and 5 h). Rat erythrocyte CA
      activity was significantly inhibited by pharmacological dosage of the ethanol (2
      mL.kg(- 1)) for up to 3 h (p < 0.001) following intraperitoneally administration.
      The ethanol showed in vitro inhibitory effects on HCA-I and HCA-II hydratase
      activity, determined by colorimetrically using the CO(2)-hydratase method. The
      inhibitor concentrations causing up to 50% inhibition (IC(50)) were 2.09 M for
      HCA-I (r(2):0.9273) and 1.83 M for HCA-II (r(2):9749). In conclusion, it was
      demonstrated that carbonic anhydrase enzyme in erythrocytes was significantly
      inhibited by the ethanol both in in vitro and in vivo.

PMID- 18343915
TI  - Carbonic anhydrase inhibition. Insight into the characteristics of zonisamide,
      topiramate, and the sulfamide cognate of topiramate.
AB  - Some useful therapeutic agents inhibit certain carbonic anhydrase (CA) isozymes
      to varying degrees. We have conducted enzyme kinetics studies in a 4-nitrophenyl
      acetate (4-NPA) hydrolysis assay with the marketed antiepileptic drugs topiramate
      (1) and zonisamide (2) to determine if their full inhibition of human CA-II and
      CA-I requires extended preincubation conditions. We found that neither 1 nor 2
      requires appreciable preincubation with either enzyme to manifest full inhibitory
      activity. We also examined the sulfamide cognate of topiramate (3) to
      characterize its CA inhibitory activity, and confirmed that it is a very weak
      inhibitor, unlike 1 or 2. In a CO(2) hydration assay, 3 behaved as a very weak,
      partial inhibitor of CA-II and CA-I. We conclude that topiramate (1), zonisamide
      (2), and sulfamide 3 do not require extended exposure to human CA-I or CA-II to
      manifest full inhibitory activity (4-NPA assay).

PMID- 18343916
TI  - Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole
      derivatives.
AB  - In this study, new 3-[(1(2H)-phthalazinone-2-yl(methyl/ethyl]-4-aryl-1,2,4
      triazole-5-thione and 2-[[1(2H)-phthalazinone-2-yl]methyl/ethyl]-5-arylamino
      1,3,4-thiadiazole derivatives were synthesized. Antimicrobial properties of the
      title compounds were investigated against two Gram (+) bacteria (S. aureus, B.
      subtilis), two Gram ( - ) bacteria (P. aeruginosa, E. coli) and two yeast-like
      fungi (C. albicans and C. parapsilosis) using the broth microdilution method.
      Generally the compounds were found to be active against B. subtilis and the
      fungi. Derivatives carrying a 1,3,4-thiadiazole ring generally showed higher
      antimicrobial activity against B. subtilis and the fungi when compared to other
      synthesized compounds.

PMID- 18343917
TI  - Antimicrobial, spectral, magnetic and thermal studies of Cu(II), Ni(II), Co(II),
      UO(2)(VI) and Fe(III) complexes of the Schiff base derived from oxalylhydrazide.
AB  - The Schiff base ligand, oxalyl [( 2 - hydroxybenzylidene) hydrazone]
      [corrected].H(2)L, and its Cu(II), Ni(II), Co(II), UO(2)(VI) and Fe(III)
      complexes were prepared and tested as antibacterial agents. The Schiff base acts
      as a dibasic tetra- or hexadentate ligand with metal cations in molar ratio 1:1
      or 2:1 (M:L) to yield either mono- or binuclear complexes, respectively. The
      ligand and its metal complexes were characterized by elemental analyses, IR, (1)H
      NMR, Mass, and UV-Visible spectra and the magnetic moments and electrical
      conductance of the complexes were also determined. For binuclear complexes, the
      magnetic moments are quite low compared to the calculated value for two metal
      ions complexes and this shows antiferromagnetic interactions between the two
      adjacent metal ions. The ligand and its metal complexes were tested against a
      Gram + ve bacteria (Staphylococcus aureus), a Gram -ve bacteria (Escherichia
      coli), and a fungi (Candida albicans). The tested compounds exhibited high
      antibacterial activities.

PMID- 18343919
TI  - Use of digital tomosynthesis: case report of a suspected scaphoid fracture and
      technique.
AB  - Digital tomosynthesis is a relatively new technique for producing an arbitrary
      number of slice images generated retrospectively from a sequence of projections
      acquired during a single motion of the X-ray tube. Tomosynthesis has already been
      described for mammographic and thoracic applications to reduce overlap of
      tissues. We present a case ofa 19-year-old man with a suspected scaphoid fracture
      in which we used digital tomosynthesis to confirm the diagnosis and thus excluded
      the need for other imaging modalities. We also describe the technique and
      background of tomosynthesis with possible future indications for this new
      promising technique.

PMID- 18343920
TI  - The radiographic acromiohumeral interval is affected by arm and radiographic beam
      position.
AB  - OBJECTIVE: The objective was to determine whether arm and radiographic beam
      positional changes affect the acromiohumeral interval (AHI) in radiographs of
      healthy shoulders. MATERIALS AND METHODS: Controlling for participant's height
      and position as well as radiographic beam height and angle, from 30 right
      shoulders of right-handed males without shoulder problems four antero-posterior
      (AP) radiographic views each were obtained in defined positions. Three
      independent, blinded physicians measured the AHI to the nearest millimeter in 120
      randomized radiographs. Mean differences between measurements were calculated,
      along with a 95% confidence interval. RESULTS: Controlling for observer effect,
      there was a significant difference between AHI measurements on different views
      (p< 0.01). All pair-wise differences were statistically significant after
      adjusting for multiple comparisons (all p values<0.01). CONCLUSIONS: Even in
      healthy shoulders, small changes in arm position and radiographic beam
      orientation affect the AHI in radiographs.

PMID- 18343921
TI  - Spontaneous immune responses to sporadic tumors: tumor-promoting, tumor
      protective or both?
AB  - Cancer cells cannot develop into invasive cancers without interactions with cells
      and soluble mediators present in the tumor microenvironment. Accumulating
      evidence indicates that the immune system is a critical determinant of malignant
      outgrowth; however, the tumor-modulating effects of spontaneous immune responses
      towards nascent malignancies are rather paradoxical. Both cancer-protective and
      cancer-promoting features of the immune system have been described. This review
      will discuss the role of the dynamic inflammatory tumor microenvironment during
      cancer development and progression, and will focus on the intriguing question:
      "Do malignancies develop in spite of-or because of-spontaneous immune responses?"
      Special emphasis will be put on recent progress in our understanding of the
      immune system's double-edged sword function during de novo carcinogenesis.

PMID- 18343922
TI  - Protein-bound polysaccharide K augments IL-2 production from murine mesenteric
      lymph node CD4+ T cells by modulating T cell receptor signaling.
AB  - The protein-bound polysaccharide isolated from basidiomycetes (PSK), a biological
      response modifier, has been used as immunotherapeutic agent for the treatment of
      cancers. It has been demonstrated previously that PSK activates various types of
      immune cells in vitro, and orally administrated PSK activates anti-tumor CD4+ T
      cell response in mesenteric lymph nodes (MLNs). The detailed mechanism of action
      of PSK, however, has not been elucidated yet. The objective of the present study
      was to clarify the molecular mechanism of immunopotentiating effects of PSK using
      primary culture of the MLN CD4+ T cells. T cell receptor (TCR) stimulation
      induced interleukin-2 production from MLN CD4+ T cells was significantly
      augmented by PSK in a concentration-dependent manner, and the augmentation was
      reflected at mRNA level. Furthermore, PSK augmented transcriptional activities of
      nuclear factor of activated T cells and activator protein 1, and phosphorylation
      of extracellular signal-regulated kinase 1/2 and linker for activation of T cells
      induced by TCR stimulation, whereas PSK had no influences without TCR
      stimulation. Collectively, the results indicate that PSK augments activation of
      MLN CD4+ T cells, probably by modulating the TCR signaling, and provide important
      knowledge for the elucidation of the true target molecule(s) of PSK.

PMID- 18343923
TI  - Gamma-IFN-inducible-lysosomal thiol reductase modulates acidic proteases and HLA
      class II antigen processing in melanoma.
AB  - HLA class II-restricted antigen (Ag) processing and presentation are important
      for the activation of CD4+ T cells, which are the central orchestrating cells of
      immune responses. The majority of melanoma cells either expresses, or can be
      induced to express, HLA class II proteins. Thus, they are prime targets for
      immune mediated elimination by class II-restricted CD4+ T cells. We have
      previously shown that human melanoma cells lack an important enzyme, gamma
      interferon-inducible lysosomal thiol-reductase (GILT), capable of perturbing
      immune recognition of these tumors. Here, we show that GILT expression in human
      melanoma cells enhances Ag processing and presentation via HLA class II
      molecules. We also show that GILT expression influences the generation of active
      forms of cysteinyl proteases, cathepsins B, L and S, as well as an aspartyl
      protease cathepsin D in melanoma cells. Mechanistic studies revealed that GILT
      does not regulate acidic cathepsins at the transcriptional level; rather it
      colocalizes with the cathepsins and influences HLA class II Ag processing. GILT
      expression in melanoma cells also elevated HLA-DM molecules, which favor epitope
      loading onto class II in the endolysosomal compartments, enhancing CD4+ T cell
      recognition. These data suggest that GILT-expressing melanoma cells could prove
      to be very promising for direct antigen presentation and CD4+ T cell recognition,
      and may have direct implications for the design of cancer vaccines.

PMID- 18343924
TI  - Phase I dose-escalating study of 24-h continuous infusion of 5-fluorouracil in
      combination with weekly docetaxel and cisplatin in patients with advanced gastric
      cancer.
AB  - PURPOSE: To determine the maximum-tolerated dose (MTD) of a 24-h continuous
      infusion of 5-fluorouracil (5-FU) when administered in combination with a fixed
      weekly dose of docetaxel and cisplatin in patients with advanced gastric cancer.
      METHODS: Patients with advanced gastric adenocarcinoma (n = 21) received a weekly
      regimen of docetaxel, cisplatin and 5-FU (DCF) for 3 consecutive weeks every 4
      weeks. The doses of docetaxel and cisplatin were fixed at 33.3 and 30 mg/m(2),
      respectively. The dose of 5-FU was increased from a starting dose of 1,000
      mg/m(2) to the MTD. RESULTS: A total of 53 cycles of chemotherapy were
      administered (median = 3 cycles/patient). The MTD of 5-FU was 1,750 mg/m(2). All
      21 patients were assessed for toxicity and 19 patients (90%) were evaluated for
      response. Both grade 3-4 hematologic and non-hematologic toxicities occurred in
      less than 10% of patients and there were no treatment-related deaths. Among the
      19 patients, we observed 1 complete and 4 partial responses for an overall
      response rate of 26% (95% CI: 6-46%). This rate increased to 39% (95% CI: 12-66%)
      in 13 chemotherapy-naive patients. CONCLUSIONS: A consecutive weekly DCF regimen
      at 4-week intervals appears feasible for advanced gastric cancer with a favorable
      toxicity profile. The recommended doses are 33.3 mg/m(2) of docetaxel, 30 mg/m(2)
      of cisplatin and 1,500 mg/m(2) of a 24-h continuous intravenous infusion of 5-FU.
      The response of this weekly regimen in our study was favorable and deserved
      further investigation in a phase II trial.

PMID- 18343925
TI  - Effectiveness of pharmacokinetic modulating chemotherapy combined with cisplatin
      as induction chemotherapy in resectable locally advanced head and neck cancer:
      phase II study.
AB  - PURPOSE: To test the efficacy and safety of pharmacokinetic modulating
      chemotherapy combined with cisplatin (PMC-cisplatin) as induction chemotherapy
      (ICT) before definitive treatment in patients with respectable locally advanced
      head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Patients
      with stage III-IV resectable locally advanced HNSCC were enrolled. All eligible
      patients received PMC-cisplatin regimen as ICT containing intravenous leucovorin
      250 mg/m(2) and 5-FU 600 mg/m(2) on day 1, oral tegafur-uracil (UFUR) 250
      mg/m(2)/day on days 1-5, repeated every week for six courses. Cisplatin 100
      mg/m(2 )was given during the first and fourth courses of PMC. For ICT responders,
      concurrent chemoradiotherapy (CRT) with cisplatin/tegafur-uracil/70 Gy
      radiotherapy was performed. Salvage surgery plus postoperative CRT was given to
      ICT non-responders. RESULTS: The overall response rate of PMC-cisplatin as ICT
      was 76%, including a complete remission rate of 23%. The overall organ
      preservation rate of the multimodality treatment was 75%, with 97% in ICT
      responders. At a median follow-up of 25 months, 47% of the patients were still
      alive and disease-free. The superiority of disease-free survival was demonstrated
      in ICT responders. The 3-year overall survival rate was 67%. The toxicity of
      treatment was acceptable. CONCLUSIONS: Application of PMC-cisplatin as the
      induction chemotherapy before definitive treatment provides a promising result in
      treatment response and survival of advanced HNSCC. This regimen is effective and
      safe, and further studies considering the combination of PMC with other
      chemotherapeutics such as taxanes to improve the clinical outcome of advanced
      HNSCC is warranted.

PMID- 18343926
TI  - Functional characterization of the CgPGS1 gene reveals a link between
      mitochondrial phospholipid homeostasis and drug resistance in Candida glabrata.
AB  - Cardiolipin and its precursor phosphatidylglycerol are two anionic phospholipids
      that are essential for the biogenesis of functional mitochondria. To assess their
      role in mitochondrial and cellular functions in the pathogenic yeast Candida
      glabrata, a functional characterization of the CgPGS1 gene encoding the
      phosphatidylglycerolphosphate synthase has been carried out. Transposon insertion
      mutation in CgPGS1 resulted in the loss of phosphatidylglycerolphosphate synthase
      activity and in deficiency of both phosphatidylglycerol and cardiolipin. The
      Cgpgs1 Delta mutant cells displayed reduced amounts of cytochrome b and
      cytochrome a, and had impaired growth on minimal media containing non-fermentable
      carbon and energy sources. They did not grow at elevated temperatures and failed
      to form colonies after induction of mitochondrial DNA deletions. The mutant cells
      also displayed a decreased susceptibility to fluconazole, ketoconazole,
      clotrimazole, voriconazole and posaconazole. In the Cgpgs1 Delta mutant, a
      quantitative real time PCR revealed enhanced mRNA levels for multidrug resistance
      associated genes such as CgPDR1 encoding transcriptional activator and CgCDR1,
      CgPDH1 and CgSNQ2 coding for drug efflux transporters. These results indicate
      that CgPGS1 and anionic phospholipids are required for optimal mitochondrial
      functions and maintenance of yeast susceptibility to azole antifungals.

PMID- 18343927
TI  - First experiences with contrast-enhanced first-pass MR perfusion imaging in
      patients with primary, benign cardiac masses and tumour-like lesions.
AB  - The aim of this study was to evaluate the diagnostic value of contrast-enhanced
      first-pass perfusion MRI in patients with suspected cardiac masses and tumour
      like lesions. Twenty patients underwent contrast-enhanced first-pass saturation
      recovery steady-state-free-precession perfusion MRI in addition to clinical MRI.
      Eleven diagnostic parameters were analysed blinded in consensus by three
      observers: localisation (paracardiac/mural/intracavitary), malignancy
      (benign/malignant) and first-pass enhancement pattern (homogeneous/heterogeneous
      as well as non-perfused/hypoperfused/iso-perfused/ hyperperfused). The results
      were compared to combined references comprising histology, cytology, medical and
      surgical reports, echocardiography, chest X-ray, coronary angiography and regular
      MRI. Also, we analysed if additional first-pass perfusion confirmed, changed or
      reduced the number of differential diagnoses compared to clinical MRI. All
      cardiac masses or tumour-like lesions were correctly localised and scored as
      benign lesions. For homogeneous perfused lesions the sensitivity, specificity,
      positive and negative predictive value was 94/100/100/67%, 100/94/67/100% for
      heterogeneous perfused lesions, 92/100/100/88% for non-perfused, 100/94/75/100
      for hypoperfused, 100/100/100/100% for hyperperfused and for isoperfused lesions.
      In 17/2/1 cases perfusion MRI confirmed, reduced or increased the number of
      potential differentials. First-pass perfusion MRI provides valuable information
      in patients with benign cardiac masses or tumour-like lesions. Further experience
      is needed to underline these preliminary observations.

PMID- 18343928
TI  - Murine liver implantation of radiation-induced fibrosarcoma: characterization
      with MR imaging, microangiography and histopathology.
AB  - We sought to establish and characterize a mouse liver tumor model as a platform
      for preclinical assessment of new diagnostics and therapeutics. Radiation-induced
      fibrosarcoma (RIF-1) was intrahepatically implanted in 27 C3H/Km mice. Serial in
      vivo magnetic resonance imaging (MRI) with a clinical 1.5-T-magnet was performed
      using T1- (T1WI), T2- (T2WI), and diffusion-weighted sequences (DWI), dynamic
      contrast-enhanced MRI (DCE-MRI), and contrast-enhanced T1WI, and validated with
      postmortem microangiography and histopathology. Implantation procedure succeeded
      in 25 mice with 2 deaths from overdosed anesthesia or hypothermia. RIF-1 grew in
      21 mice with volume doubling time of 2.55+/-0.88 days and final size of 216.2+/
      150.4 mm(3) at day 14. Three mice were found without tumor growth and one only
      with abdominal seeding. The intrahepatic RIF-1 was hypervascularized with
      negligible necrosis as shown on MRI, microangiography and histology. On DCE-MRI,
      maximal initial slope of contrast-time curve and volume transfer constant per
      unit volume of tissue, K, differed between the tumor and liver with only the
      former significantly lower in the tumor than in the liver (P<0.05). Liver
      implantation of RIF-1 in mice proves a feasible and reproducible model and
      appears promising for use to screen new diagnostics and therapeutics under
      noninvasive monitoring even with a clinical MRI system.

PMID- 18343929
TI  - Endoscopic third ventriculostomy for obstructive hydrocephalus in children
      younger than 6 months of age: is it a first-choice method?
AB  - INTRODUCTION: Endoscopic third ventriculostomy (ETV) is considered a safe
      procedure and is a method of choice in treatment of obstructive hydrocephalus
      nowadays. In case of Sylvian aqueduct stenosis, the success rate reaches 90%. In
      children younger than 6 to 24 months, respectively, however, some authors report
      lower effectiveness ranging between 0% and 64%. The reasons of ETV failure are
      discussed: hyporesorption in patients with obstruction as a consequence of
      hemorrhage or infection, suboptimal ETV performance, especially in premature
      newborns, or the theory of different cerebrospinal fluid circulation in newborn
      babies. MATERIALS AND METHODS: Between January 2005 and December 2006 in our
      clinic, 14 patients younger than 6 months having presented with obstructive
      hydrocephalus were treated endoscopically. Obstruction was revealed by
      preoperative magnetic resonance imaging. The etiology of hydrocephalus was
      congenital aqueduct stenosis in five patients, posthemorrhagic obstruction in
      eight patients, and combination of posthemorrhagic and postinfection etiology in
      one patient. ETV was considered successful when no shunt operation was needed in
      the patient. RESULTS: ETV was successful in eight patients who experienced
      regression of signs of intracranial hypertension and were not forced to undergo
      ventriculo-peritoneal (V-P) shunting. In one patient, a successful repeat ETV was
      performed. In the remaining six patients, V-P shunt implantation was necessary.
      Total success rate in our group of patients was 57%. The only complication was
      subdural hygroma in one patient requiring evacuation. CONCLUSION: Based on our
      experience, we recommend ETV as the method of choice in children younger than 6
      month of age.

PMID- 18343930
TI  - Spectrum of skull base tumors in children and adolescents: a series of 42
      patients and review of the literature.
AB  - OBJECTIVE: This study aims to contribute to the collective experience with the
      treatment of those skull base tumors exceptionally arising in children and
      adolescents. MATERIALS AND METHODS: We retrospectively reviewed 42 patients
      younger than 19 years and operated on for a skull base tumor between 1992 and
      2002. We analyzed data regarding patient age, histology, tumor location, extent
      of resection, postoperative complications, and adjuvant therapies. Long-term
      outcomes were also tracked (functional sequelae, recurrence, mortality).
      CONCLUSION: The median age was 13.75 years. Twenty-two patients harbored a
      malignant tumor. Gross total resection was achieved for 78% of cases. Transient
      postoperative cerebrospinal fluid leak or infection affected ten patients,
      suggesting the need for reconstructive techniques. Nineteen patients received
      adjuvant therapy. Recurrence rate was 47%. At the end of the follow-up (median =
      63 months), 14% of patients had a neurological deficit and 30% were dead. Middle
      cranial base tumors were associated with a poor prognosis.

PMID- 18343931
TI  - Colorectal cancer in the elderly: surgical treatment and long-term survival.
AB  - BACKGROUND AND AIMS: The prognosis of radical treatment for colorectal cancer in
      elderly patients has been subject of controversies. The aim of this study was to
      compare patients at the age of 75 years or older with a group of younger
      patients, focused on the clinicopathologic characteristics and the results of
      radical treated colorectal cancer. PATIENTS AND METHODS: A retrospective study
      was made to evaluate age-related surgical risk and outcome. The following
      criteria were analyzed in two age groups (<75 years and > or =75 years):
      comorbidities, tumor characteristics, type of resection, postoperative morbidity
      and mortality, recurrence rate, overall survival, cancer-related survival, and
      disease-free survival. RESULTS: Altogether, 517 patients were included into the
      study. Gender, ASA risk score, frequency of concomitant comorbidities, and tumor
      location differed significantly between the two age groups. Tumor characteristics
      were equal between the two groups. There were no differences in 30-day morbidity
      except in postoperative bleeding, but 30-day mortality was higher in the older
      age group. Mean time of follow-up was approximately 32 months. Frequencies for
      adjuvant, as well as for palliative (radio-) chemotherapy were lower in the older
      group. While cancer-related survival was lower in the higher age group, there
      were no differences in disease-free survival. CONCLUSION: The age of patients
      does not seem to be a prognostic factor for perioperative results; furthermore,
      the long-term results rather depend on the stage of disease and on adjuvant or
      palliative treatment, respectively, than on age.

PMID- 18343932
TI  - Human neuromelanin induces neuroinflammation and neurodegeneration in the rat
      substantia nigra: implications for Parkinson's disease.
AB  - Parkinson's disease (PD) is a common neurodegenerative disorder characterized by
      a selective loss of dopaminergic neurons in the substantia nigra (SN). It has
      been suggested that microglial inflammation augments the progression of PD.
      Neuromelanin (NM), a complex polymer pigment found in catecholaminergic neurons,
      has sparked interest because of the suggestion that NM is involved in cell death
      in Parkinson's disease, possibly via microglia activation. To further investigate
      the possible role of NM in the pathogenesis of PD, we conducted in vivo
      experiments to find out whether microglial cells become activated after injection
      of human neuromelanin (NM) into (1) the cerebral cortex or (2) the substantia
      nigra to monitor in this PD-relevant model both microglial activation and
      possible neurodegeneration. In this study, adult male Wistar rats received an
      intracerebral injection of either NM, bacterial lipopolysaccharide (LPS, positive
      control), phosphate-buffered saline (PBS, negative control) or colloidal gold
      suspension (negative particular control). After different survival times (1, 8 or
      12 weeks), brain slices from the cerebral cortex or substantia nigra (SN, 1 week)
      were stained with Iba-1 and/or GFAP antibody to monitor microglial and astrocytic
      reaction, and with tyrosine hydroxylase (TH) to monitor dopaminergic cell
      survival (SN group only). The injection of LPS induced a strong inflammatory
      response in the cortex as well in the substantia nigra. Similar results could be
      obtained after NM injection, while the injection of PBS or gold suspension showed
      only moderate or no glial activation. However, the inflammatory response declined
      during the time course. In the SN group, there was, apart from strong microglia
      activation, a significant dopaminergic cell loss after 1 week of survival time.
      Our findings clearly indicate that extracellular NM could be one of the key
      molecules leading to microglial activation and neuronal cell death in the
      substantia nigra. This may be highly relevant to the elucidation of therapeutic
      strategies in PD.

PMID- 18343933
TI  - Inter-laboratory comparison of neuropathological assessments of beta-amyloid
      protein: a study of the BrainNet Europe consortium.
AB  - Amyloid-beta-protein (Abeta) is generally assessed by neuropathologists in
      diagnostics. This BrainNet Europe ( http://www.brainnet-europe.org/ ) (15 centres
      and 26 participants) study was carried out to investigate the reliability of such
      an assessment. In the first part of this trial, tissue microarray sections were
      stained with the antibody of each centre's choice. Reflecting the reality, seven
      antibodies and a plethora of pretreatment strategies were used. Ninety-two
      percent of the stainings were of good/acceptable quality and the estimation of
      presence of Abeta aggregates yielded good results. However, a poor agreement was
      reached particularly regarding quantitative (density) and qualitative
      (diffuse/cored plaques) results. During a joint meeting, the clone 4G8 was
      determined to label best the fleecy/diffuse plaques, and thus, this clone and the
      formic acid pretreatment technique were selected for the second part of this
      study. Subsequently, all stained sections were of good/acceptable quality and
      again a high level of concordance of the dichotomized (presence/absence)
      assessment of plaques and CAA was achieved. However, even when only one antibody
      was used, the type of Abeta-aggregates (diffuse/cored), type of vessel and
      Vonsattel grade, were not reliably assigned. Furthermore, the quantification of
      lesions was far from reliable. In line with the first trial, the agreement while
      assessing density (some, moderate and many) was unimpressive. In conclusion, we
      can confirm the utility of immunohistochemical detection of Abeta-protein in
      diagnostics and research. It is noteworthy that to reach reproducible results a
      dichotomized assessment of Abeta-immunoreactivity rather than quantification and
      assignment of various types of lesions should be applied, particularly when
      comparing results obtained by different neuropathologists.

PMID- 18343934
TI  - A long-standing incomprehensible matter of obstetrics: meconium-stained amniotic
      fluid, a new approach to reason.
AB  - OBJECTIVE: We sought to determine whether meconium-stained amniotic fluid is
      based on chronic hypoxia or not? In case of chronic hypoxia, higher red blood
      cell (Rbc) count and/or total hemoglobin levels (Hgb) and/or higher fetal
      hemoglobin (HbF) and/or lower adult hemoglobin (HbA) levels were expected when
      compared with controls. DESIGN: Case-control study. SETTING: Obstetric unit of a
      tertiary ministry of health hospital. SAMPLE: Fifty singleton pregnancies with
      meconium-stained amniotic fluid and 50 singleton pregnancies with clear amniotic
      fluid at all stages of labor. METHODS: Umbilical cord blood samples were
      collected for determination of total blood parameters and hemoglobin
      electrophoresis. MAIN OUTCOME MEASURES: Red blood cell count, total hemoglobin,
      fetal and adult hemoglobin contents (HbF and HbA). RESULTS: Red blood cell count,
      total hemoglobin, fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents were
      not different between meconium stained and clear amniotic fluid groups.
      CONCLUSION: These results suggest that meconium passage may not be associated
      with chronic fetal hypoxia as demonstrated by similar red blood cell count, total
      hemoglobin values and fetal hemoglobin (HbF) and adult hemoglobin (HbA) contents.

PMID- 18343935
TI  - Chondromatous differentiation in clear cell carcinoma of the ovary: a rare
      finding challenging the differential diagnosis.
AB  - OBJECTIVE: Ovarian surface epithelial tumors rarely have heterologous elements
      including bone or cartilage that may appear histologically benign or malignant.
      There are a few case reports in the literature of ovarian tumors containing
      chondromatous areas. CASE: We report a clear cell carcinoma of the bilateral
      ovary showing chondromatous differentiation in a 56-year-old woman.
      Histopathologic study of the specimen showed clear cell carcinoma with many small
      foci of chondromatous differentiation. Immunohistochemical studies demonstrated
      positivity for S-100 confirming the diagnosis. The patient was alive with disease
      on chemotherapy for 16 months. CONCLUSION: A rare case of benign appearing
      chondromatous differentiation in an ovarian clear cell carcinoma of the ovary is
      described, and the significance of this finding is discussed.

PMID- 18343936
TI  - T lymphocytes (CD3) may participate in the recurrence of cervical intraepithelial
      neoplasia grade III.
AB  - OBJECTIVE: Data from the literature demonstrate that the local and systemic
      immune responses seem to play an important role in the progression of cervical
      intraepithelial neoplasia (CIN). Our aim was to investigate whether recurrences
      among CIN III patients might be related to the presence of local lymphocytes,
      macrophage and enzyme iNOS. METHODS: We analyzed 35 patients with CIN III who
      underwent conization and followed up for a minimum of 4 years. Using
      immunohistochemistry, the presence of T lymphocytes (CD3, CD8 and CD45RO), B
      lymphocytes (CD20), macrophages (CD68) and the expression of the enzyme iNOS were
      investigated. The quantity of marked cells is graded as: 0, absence of cells; 1,
      rare cells; 2, moderate number of cells; 3, many cells. For statistical purposes,
      we took the scores 0 and 1 to indicate weak marking and the scores 2 and 3 to
      indicate strong marking. RESULTS: We found strong positive expression of CD3
      positive T lymphocytes among CIN III patients with recurrence following
      conization (100 vs. 50% without recurrence, p=0.02). We did not find any
      statistical differences in the expression of CD20, CD68, CD45RO, CD8 or iNOS.
      CONCLUSIONS: It is concluded that strong positive findings of CD3 T lymphocytes
      were related to recurrence following conization due to CIN III.

PMID- 18343937
TI  - Ethnic variation and variability of fetal nasal bone length at 11-15 weeks of
      gestation in a Brazilian population: preliminary results.
AB  - OBJECTIVE: To evaluate the maternal ethnic influence and the intra and
      interobserver reproducibility of the nasal bone length measurement at 11-15 weeks
      of gestation in a Brazilian population. METHODS: A cross-sectional study with 171
      normal pregnant women at 11-15 weeks was performed. Nasal bone was
      transabdominally measured in all cases. The patients were separated into three
      racial groups (White, Black and Asian) according to maternal ethnicity. The
      intraobserver variability was calculated through the repeated measurement of 55
      fetuses by a single observer, and the interobserver variability was calculated
      through 44 measurements by two observers. The ANOVA test was used to compare the
      three racial groups. To calculate the variability, the intraobserver correlation
      coefficient (intra-CC), the interclass correlation coefficient (inter-CC) with
      95% confidence interval, and the Bland-Altman plots were used. RESULTS: No
      statistically significant difference could be observed among the three races as
      for nasal bone length measurement (P = 0.934). The intraobserver variability was
      considered very good [intra-CC 0.92-IC 95% (0.902; 0.947)], as well as the
      interobserver variability [inter-CC 0.91-IC 95% (0.873; 0.940)]. CONCLUSIONS:
      There is no significant difference in nasal bone length measurement among the
      three races analyzed. Nasal bone length measurement is reproducible.

PMID- 18343938
TI  - Re-laparotomy after cesarean section: operative complications in surgical
      delivery.
AB  - OBJECTIVE: To determine the risk factors causing re-laparotomy and the
      indications, management and outcomes of re-laparotomy after a cesarean section.
      METHODS: We had, during the study period of January 2002 to January 2007, 28,799
      cesarean sections and 35 cases with re-laparotomy. We studied the patients' age,
      parity, indications for cesarean section and indications for re-laparotomy, time
      interval after cesarean section to reopening of the abdomen, type of surgery,
      need for blood transfusion and span of hospital stay. RESULTS: The incidence of
      re-laparotomy was 0.12%. Cases with placental abruption and previous cesarean >
      or =3 had a higher risk for re-laparotomy. Procedures that were performed at re
      laparotomy were drainage and resuturing of hematomas (n = 8), resuturing of
      uterus and securing hemostasis with stitches (n = 10), bladder repair (n = 1),
      herniation repair (n = 1), total abdominal hysterectomy (n = 2), subtotal
      abdominal hysterectomy (n = 5), and draining and resuturing of broad ligament,
      parametrium, abdominal wound, and cutaneous and subcutaneous tissue due to
      infection and abscess formation (n = 8). Two cases required admission into the
      intensive care unit. We had one case with maternal mortality. Majority of the
      complications were revealed at an early period and these were hemorrhagic cases
      mostly. CONCLUSION: Although the rate of re-laparotomy after cesarean section is
      low, several actions must be undertaken to decrease the need for re-laparotomy.
      In particular, cases with placental abruption and previous cesarean > or =3 are
      with higher risk for re-laparotomy and have a 15-fold risk for re-laparotomy
      after cesarean section.

PMID- 18343939
TI  - The effects of spirulina on allergic rhinitis.
AB  - The prevalence of allergic rhinitis is increasing globally due to various causes.
      It affects the quality life of a large group of people in all around the world.
      Allergic rhinitis still remains inadequately controlled with present medical
      means. The need of continuous medical therapy makes individuals anxious about the
      side effects of the drugs. So there is a need for an alternative strategy.
      Effects of spirulina, tinospora cordifolia and butterbur were investigated
      recently on allergic rhinitis in just very few investigations. Spirulina
      represents a blue-green alga that is produced and commercialized as a dietary
      supplement for modulating immune functions, as well as ameliorating a variety of
      diseases. This double blind, placebo controlled study, evaluated the
      effectiveness and tolerability of spirulina for treating patients with allergic
      rhinitis. Spirulina consumption significantly improved the symptoms and physical
      findings compared with placebo (P < 0.001***) including nasal discharge,
      sneezing, nasal congestion and itching. Spirulina is clinically effective on
      allergic rhinitis when compared with placebo. Further studies should be performed
      in order to clarify the mechanism of this effect.

PMID- 18343940
TI  - The effect of thalidomide on neovascularization in a mouse model of retinopathy
      of prematurity.
AB  - PURPOSE: Abnormal angiogenesis is the hallmark feature of retinopathy of
      prematurity (ROP), and contributes to the severe visual loss that accompanies
      this disease. Thalidomide is a well-known anti-angiogenic drug. We tested the
      assumption that injection of intraperitoneal thalidomide could reduce the
      severity of oxygen-induced retinopathy (OIR) in a mouse model. METHODS: Forty
      three baby wild type mice were used in this study. The mouse model of oxygen
      induced retinopathy consisted of a 5-day exposure to 75% oxygen from postnatal
      day 7 to 12 (P12) followed by 5 days in room air (relative hypoxia). Control mice
      were those with normally developing retinal vasculature exposed to room air from
      birth until postnatal day 17 (P17). Thalidomide (200 mg/Kg) was administered
      daily intraperitoneally to control and ROP mice in two protocols: (1) from P12 to
      P16, and (2) from P11 to P15 . Fluorescein-conjugated dextran angiography of
      retinal vasculature was performed on P17, and retinal whole mounts were prepared
      to score features of retinopathy. The parameters that were scored in a masked
      fashion included blood vessel growth, blood vessel tufts formation, extra retinal
      neovascularization, degree of central constriction, and tortuosity of vessels.
      These parameters constitute the Modified Retinopathy Scoring System (MRSS). In
      addition, quantification of the number of blood vessel tufts was performed in a
      masked fashion with hematoxylin & eosin (H&S) staining of paraffin-embedded eye
      sections. RESULTS: The retinopathy score by MRSS in the thalidomide treated mice
      was similar to that of untreated mice that were exposed to oxygen (9.3 +/- 1.9 vs
      10.15 +/- 1.6; p = 0.21). The neovascularization count was also similar between
      the two groups (10.4 +/- 5.6 vs 9.6 +/- 4.8; p = 0.56). In the control group left
      in the room air, the retinopathy score was 0.19 +/- 0.37 (p = 0) and the
      neovascularization count was also very low (2.92 +/- 2.14; p = 0). CONCLUSIONS:
      Although thalidomide might have a proven anti-angiogenic and anti-inflammatory
      effect, our model did not show a significant effect on the retinopathy. The
      reason might be an ineffective level of the drug in the retina due to ineffective
      metabolism of the drug, or due to blockage of the drug by the blood-retina
      barrier, or the involvement of other factors besides those influenced by
      thalidomide in the process.

PMID- 18343941
TI  - Analysis of the prognostic factors and evaluation of surgical treatment for
      synchronous liver metastases from gastric cancer.
AB  - BACKGROUND AND AIMS: Whether or not a synchronous resection of liver metastases
      from gastric cancer provides a survival benefit has been a key issue. We identify
      the significant prognostic factors and clarify the beneficial effect on the
      survival of liver surgical treatment. MATERIALS AND METHODS: We reviewed 72
      patients who underwent a gastrectomy for gastric cancer with synchronous liver
      metastases and classified the liver metastases into three grades, such as H1:
      metastases were limited to one of the lobes, H2: there were a few scattered
      metastases in both lobes, and H3: there were numerous scattered metastases.
      RESULTS: H1, 2 metastases, and an absence of peritoneal dissemination (P0) were
      significantly independent prognostic factors for liver metastases of gastric
      cancer. In addition, the cumulative 1 and 5-year survival rates of liver surgical
      treatment (hepatic resection and/or microwave coagulation therapy) were 80.0% and
      60.0%, whereas the survival rates for non-hepatic surgical treatment were 36.4%
      and 0% in 26 patients with H1, 2, and P0. In those patients, the radical
      operation, the solitary metastatic liver tumor, and no-distant lymph node
      metastases were independent prognostic determinants of survival. CONCLUSION: The
      radical operation including the surgical treatment for metastatic liver tumors
      should be performed to improve the prognosis in gastric cancer patients with
      synchronous H1, 2, and P0.

PMID- 18343942
TI  - Age, microbiology and prognostic scores help to differentiate between secondary
      and tertiary peritonitis.
AB  - BACKGROUND AND AIMS: Tertiary peritonitis is a severe persisting intra-abdominal
      infection and associated with high mortality. The aim was to find significant
      risk factors for mortality and tertiary peritonitis including the Mannheim
      Peritonitis Index (MPI), the Acute Physiology and Chronic Health Evaluation
      (APACHE) II score, and a sumscore of both. MATERIALS AND METHODS: In this
      retrospective single-center cohort study, 122 patients were treated at the
      Surgical Department of a University Hospital. RESULTS: Sixty-nine patients
      (56.6%) developed tertiary peritonitis. Nineteen patients (27.5%), who suffered
      from tertiary peritonitis, died in contrast to eight patients (15.1%) with
      secondary peritonitis (P = 0.101). Patients with tertiary peritonitis had
      significantly higher APACHE II (P < 0.001), MPI (P = 0.035), and combined APACHE
      II and MPI scores (P < 0.001) than patients with secondary peritonitis. Age (P =
      0.035), fungal infections (P = 0.025), and infections with more than one
      microbial organism (P = 0.047) were predictive for tertiary peritonitis. Combined
      APACHE II and MPI scores detected tertiary peritonitis better than the MPI (P =
      0.014). Detection of mortality was comparable in all evaluated prognostic scores.
      CONCLUSION: Prognostic scores besides age and fungal infections are risk factors
      for mortality and help to differentiate between secondary and tertiary
      peritonitis. The combination of prognostic scores is comparable to the APACHE II
      and superior compared to the MPI in regard to detection of tertiary peritonitis.

PMID- 18343943
TI  - Half clamping of the infrahepatic inferior vena cava reduces bleeding during a
      hepatectomy by decreasing the central venous pressure.
AB  - BACKGROUND AND AIMS: Bleeding from the hepatic vein is closely related to central
      venous pressure (CVP). To evaluate the effect of low central venous pressure
      during a hepatectomy, the infrahepatic inferior vena cava (IVC) was half clamped.
      PATIENTS AND METHODS: Between 2006 and 2007, 20 patients undergoing major
      hepatectomy with the IVC half clamping (half-clamping group) were compared with
      58 patients undergoing hepatectomy without IVC half clamping between 2003 and
      2005 (control group). The types of liver resection, amount of blood loss during
      the hepatectomy, volume of blood transfusion, length of hospital stay, and
      complications were compared between the two groups. RESULTS: In the half-clamping
      group, blood loss was decreased in comparison to the control group (p = 0.041)
      and the suprahepatic CVP was low (2.4 +/- 1.8 mmHg; p = 0.0002). The diameter at
      the root of the right hepatic vein was reduced in comparison to before clamping
      (5.8 +/- 1.6 mm; p < 0.001). There were no complications of half clamping on any
      hemodynamic and blood electrolytic parameters. CONCLUSION: Using the half
      clamping technique of the IVC, intra-operative CVP was maintained below 3 mmHg
      without any side effects, and the low CVP significantly reduced the bleeding from
      hepatic veins during a major hepatectomy.

PMID- 18343944
TI  - Liver metastasis as an initial recurrence has no impact on the survival of
      patients with resectable pancreatic adenocarcinoma.
AB  - BACKGROUND: Prognosis of the patients with pancreatic adenocarcinoma is still
      poor due to a recurrence, and liver metastasis is a distant metastasis that is
      foreboded the short survival period. METHODS: Between 1999 and 2005, 68 patients
      for pancreatic adenocarcinoma underwent a pancreaticoduodenectomy (n = 17), a
      pylorus-preserving pancreaticoduodenectomy (n = 27), distal pancreatectomy (n =
      22), or total pancreatectomy (n = 2) with an extensive lymph node dissection.
      RESULTS: A tumor recurrence occurred to 55 patients (13 of the liver, 21 of the
      local recurrence, 16 of peritoneal dissemination, three of the lymph node, and
      two of lung). The low tumor grade and female demonstrated a risk factor for a
      liver metastasis (P = 0.043, P = 0.031). A logistic regression analysis
      demonstrated female (P = 0.02) and low tumor grade (P = 0.04) as independent risk
      factors for recurrence with liver metastasis. The median survival time (MST) was
      13.6 months, and MST of patients with a liver metastasis as an initial recurrent
      site was 13.7 months; the liver metastasis as an initial recurrent site has no
      impact on the MST after pancreatic resection. CONCLUSIONS: We concluded
      potentially supporting the hypothesis that even patients thought to be at higher
      risk of liver metastasis may still be given the chance of resection, considering
      the satisfying survival.

PMID- 18343945
TI  - PIK3CA, KRAS, and BRAF mutations in intraductal papillary mucinous
      neoplasm/carcinoma (IPMN/C) of the pancreas.
AB  - BACKGROUND AND AIMS: Recent studies have reported high frequencies of somatic
      mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in
      various human tumors. Three hot-spot mutations in the exons 9 and 20 have been
      proven to activate the Akt signalling pathway. The Raf/MEK/ERK (mitogen-activated
      protein kinase) signal transduction is an important mediator of a number of
      cellular fates including growth, proliferation, and survival. The BRAF gene is
      activated by oncogenic RAS, leading to cooperative effects in cells responding to
      growth factor signals. Here we evaluate the mutational status of PIK3CA, KRAS,
      and BRAF in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMNC) of the
      pancreas. MATERIALS AND METHODS: Exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 of
      PIK3CA, exons 1 of KRAS, and exons 5, 11, and 15 of BRAF were analyzed in 36
      IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA
      sequencing. RESULTS: We identified four somatic missense mutations of PIK3CA
      within the 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has
      been previously reported to be a hot-spot mutation. Furthermore, we found 17
      (47%) KRAS mutations in exon 1 and one missense mutation (2.7%) in exon 15 of
      BRAF. CONCLUSION: This data is the first report of PIK3CA mutation in pancreatic
      cancer and it appears to be the first oncogene to be mutated in IPMN/IPMC but not
      in conventional ductal adenocarcinoma of the pancreas. Our data provide evidence
      that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower
      frequency than KRAS.

PMID- 18343946
TI  - Effects of phorbol ester on vesicle dynamics as revealed by total internal
      reflection fluorescence microscopy.
AB  - Exocytosis of neurotransmitter or hormone-filled vesicles is a highly dynamic
      process regulated by various proteins and lipids. As mainly revealed indirectly
      by the electrophysiological methods, exocytosis is believed to involve multiple
      kinetic steps in which vesicles transit from one state to another. Using total
      internal reflection fluorescence microscopy which enables direct visualization of
      individual vesicles, we developed an analytical framework to track and analyze
      vesicle dynamics. We demonstrated that all subplasmalemmal vesicles generally
      undergo constant and caged Brownian motion. And they can be classified into three
      populations that differ in their motion characteristics and fusion competence.
      Furthermore, we showed that these vesicle pools are differentially modulated by
      phorbol-12-myristate-13-acetate, a phorbol ester analog to endogenous
      diacylglycerol, through both protein-kinase-C-dependent and -independent
      pathways.

PMID- 18343947
TI  - CD8 T-cell-based immunotherapy of cytomegalovirus infection: "proof of concept"
      provided by the murine model.
AB  - Adoptive transfer of antiviral effector or memory CD8 T cells is a therapeutic
      option for preventing acute cytomegalovirus (CMV) disease after primary or
      recurrent infection in immunocompromised recipients of hematopoietic stem cell
      transplantation (HSCT) aimed at curing hematopoietic malignancies. Preclinical
      research in murine models has demonstrated the power of CD8 T-cell-based
      preemptive immunotherapy and has encouraged clinical trials that gave promising
      results. The clinical evidence, however, is based primarily on statistical
      analyses indicating a reduced incidence of CMV-associated complications. Here, we
      will briefly review the data obtained from the murine model showing that CD8 T
      cells derived from CMV-immune donors and administered either as peptide-selected
      cytolytic T lymphocyte lines or after ex vivo purification by T-cell-receptor
      specific cell sorting can indeed prevent CMV-mediated histopathology and multiple
      organ failure.

PMID- 18343948
TI  - Phase II clinical trial of advanced and metastatic gastric cancer based on
      continuous infusion of 5-fluorouracil combined with epirubicin and oxaliplatin.
AB  - PURPOSE: To evaluate the efficacy and tolerability of systematic treatment of
      unresectable advanced or metastatic gastric cancer (A/MGC) based on EOF5 regimen
      (the combination of epirubicin, oxaliplatin and 5-day continuous infusion of 5
      fluorouracil). PATIENTS AND METHODS: Twenty-six patients (18 males, 8 females;
      age range, 35-72 years) with histologically confirmed metastatic (n = 23) or
      unresectable advanced (n = 3) gastric adenocarcinoma with (n = 6) or without
      previous chemotherapy (n = 20) were consented to receive EOF5 (epirubicin 50
      mg/m(2) and oxaliplatin 130 mg/m(2) on day 1, followed by continuous infusion of
      5-fluorouracil 375-425 mg/m(2) day(-1) on day 1-5), and the treatment cycle was
      repeated every 3 weeks. Responses to treatment and toxicity were evaluated every
      2 cycles. RESULTS: In the first-line treatment group of 20 patients, complete
      (CR) and partial (PR) remission were observed in two (10%) and six (30%)
      patients, respectively with an overall response rate of 40%). Eleven (55%)
      patients showed stable (SD) and one (5%) progressive disease (PD). One-year
      survival rate, time to progression (TTP) and median overall survival (OS) were
      45%, 9.7 and 12.5 months, respectively. In the second-line treatment group of six
      patients, the numbers of CR, PR, SD and PD were 0, 1, 4 and 1, respectively.
      Symptomatic response rates were 88.2, 76.9, 89.5, and 88.9% for abdominal pain,
      distention, anorexia and weight loss. The mean Karnofsky performance status score
      was increased (P < 0.001) and maintained after two and four cycles treatment. The
      major adverse events were nausea/vomiting, oral mucositis, peripheral neuropathy,
      phlebitis, constipation and myelosuppression. CTC grade 3 or 4 hematologic
      toxicities included leucopenia (7.7%), neutropenia (15.4%), thrombocytopenia
      (19.2%), and anemia (3.8%). No treatment-related deaths were recorded.
      CONCLUSIONS: EOF5 regimen shows good efficacy and an acceptable safety profile in
      A/MGC patients, and would be a suitable alternative regimen for this indication.

PMID- 18343949
TI  - Expression of fascin in thyroid neoplasms: a novel diagnostic marker.
AB  - PURPOSE: Fascin, an actin-bundling protein, is markedly upregulated in several
      epithelial tumors and its expression often correlates with high-grade, extensive
      invasion, and distant metastasis. However, reports about fascin expression in
      endocrine tumors remain rare. The aim of the present study was to assess the
      diagnostic significance of fascin in thyroid neoplasms. METHODS: Thyroid samples
      from 177 cases were examined for fascin and Ki-67 expression by
      immunohistochemistry. RESULTS: Fascin immunoreactivity was negative in normal
      follicles and nodular goiter. Fascin immunostaining was positive in 62.1% (41/66)
      of thyroid carcinomas and 26.4% (19/72) of thyroid adenomas; the difference being
      significant (P < 0.0001). In thyroid papillary carcinoma, upregulation of fascin
      was associated with both the Ki-67 labeling index and the occurrence of lymph
      node metastasis. CONCLUSION: Fascin may be a novel marker to distinguish thyroid
      carcinoma from benign lesions and may be involved in the proliferation and
      metastasis of papillary carcinoma.

PMID- 18343950
TI  - Evaluation of biomarkers for cardiotoxicity of anthracyclin-based chemotherapy.
AB  - INTRODUCTION: The clinical assessment of the myocardial damage caused by
      anthracyclin (ANT)-therapy is difficult. Therefore a study was performed to
      evaluate non-invasive markers of anthracyclin-induced cardiac effects, with
      emphasis on course-to-course variation. METHODS: Eligible for study participation
      were patients, without known cardiologic abnormalities who did not use
      cardiotoxic medication (except for ANT-therapy), who had previously completed at
      least three cycles of anthracyclin-containing chemotherapy (n = 14) and patients
      who were ANT-naive and who were scheduled to receive doxorubicin-containing
      chemotherapy (n = 12). Seven patients in this last group also completed at least
      three cycles and were available for follow-up assessments; thus a total
      population of 21 patients (12F/9M) completed at least three courses ANT
      chemotherapy. In these patients blood samples and ECG-recordings were taken
      within 6 months after completion of ANT-therapy. In 12 patients (10F/2M)
      assessments were also done before, immediately afterwards and at 24 h after each
      course of ANT. RESULTS AND CONCLUSIONS: In the patients who completed
      chemotherapy, NT-proBNP was 277% (n = 21; 95% CI: 86-661%, P < 0.001) higher
      compared to healthy volunteers. During the first course NT-proBNP rose 269% (n =
      12; 167-409%, P < 0.0001) at 24 h post-administration. The linear corrected QT
      (QTcL) directly after the first administration of ANT increased by 9.56 ms (n =
      12; 3.85-15.27, P < 0.001) and this prolongation was still present at 24 h, 11.48
      ms (n = 12; 5.61-17.34, P < 0.0001). Both NT-proBNP and QTcL returned to baseline
      before the start of the next course and a similar pattern was observed during
      each course. NT-proBNP and QTcL may be useful markers for course-to-course
      evaluation of anthracyclin-induced cardiotoxicity.

PMID- 18343951
TI  - Ommatidia of blow fly, house fly, and flesh fly: implication of their vision
      efficiency.
AB  - This work aims to elucidate the number of ommatidia or facets (the outwardly
      visible units of each ommatidium) for compound eyes in blow flies [Chrysomya
      megacephala (F.), Chrysomya rufifacies (Macquart), Chrysomya nigripes (Aubertin),
      Lucilia cuprina (Wiedemann)], house flies (Musca domestica L.), and flesh flies
      (Liosarcophaga dux Thomson) by manual counts of the corneal spreads. The head of
      the fly in each species was soaked in 20% potassium hydroxide solution at room
      temperature for 7 days, and the clear compound eye was dissected into six small
      parts, each of which was placed onto a slide and flattened using a coverslip.
      Images of each part were obtained using a microscope connected to a computer. The
      printed images of each part were magnified, and the total number of ommatidia per
      eye was manually counted. For males, the mean number of ommatidia was
      statistically different among all flies examined: L. dux (6,032) > C. rufifacies
      (5,356) > C. nigripes (4,798) > C. megacephala (4,376) > L. cuprina (3,665) > M.
      domestica (3,484). Likewise, the mean number of facets in females was
      statistically different: L. dux (6,086) > C. megacephala (5,641) > C. rufifacies
      (5,208) > C. nigripes (4,774) > L. cuprina (3,608) > M. domestica (3433).
      Scanning electron microscopy analysis of adult flies revealed the sexual
      dimorphism in the compound eye. Male C. megacephala had large ommatidia in the
      upper two thirds part and small ommatidia in the lower one third part, whereas
      only small ommatidia were detected in females. Dense postulate appearance was
      detected in the external surface of the corneal lens of the ommatidia of C.
      megacephala, C. rufifacies, and C. nigripes, while a mix of dense postulate
      appearance and variable groove array length was detected in L. cuprina and M.
      domestica. The probable functions of ommatidia are discussed with reference to
      other literature.

PMID- 18343952
TI  - Anti-Trypanosoma cruzi activity of Pterodon pubescens seed oil: geranylgeraniol
      as the major bioactive component.
AB  - In the search for new therapeutic agents for Chagas' disease, we screened
      extracts obtained from the Brazilian plant Pterodon pubescens found commercially
      in the medicinal flora market. We investigated the potential trypanocidal effect
      of the oleaginous ethanolic extract of P. pubescens seeds and its fractions (PF1,
      PF1.1, PF1.2, and PF1.3) and of geranylgeraniol (GG-OH), the sole component of
      the hexane fraction (PF1.2). In experiments with bloodstream trypomastigotes of
      Trypanosoma cruzi, performed at 37 degrees C in culture medium, PF1.2 and GG-OH
      showed similar potency, while the oleaginous extract from P. pubescens seeds and
      the other fractions were about three times less active. GG-OH inhibited the
      proliferation of intracellular amastigotes, at concentrations which do not affect
      the mammalian host cell. Transmission electron microscopy and flow cytometry
      analysis indicate the mitochondrion, an organelle that plays a central role in
      apoptosis, of both epimastigotes and of trypomastigotes as the major target of GG
      OH. On the other hand, the ultrastructural images of the endoplasmic reticulum
      profiles, myelin-like figures, and concentric membranous arrangements inside
      damaged mitochondrion are suggestive of an autophagic pathway leading to parasite
      death. Because the different forms of cell death share some morphological
      features such as mitochondrial collapse, further studies are needed to disclose
      the trypanocidal action of GG-OH.

PMID- 18343953
TI  - Beals smoothing revisited.
AB  - Beals smoothing is a multivariate transformation specially designed for species
      presence/absence community data containing noise and/or a lot of zeros. This
      transformation replaces the observed values of the target species by predictions
      of occurrence on the basis of its co-occurrences with the remaining species. In
      many applications, the transformed values are used as input for multivariate
      analyses. As Beals smoothing values provide a sense of "probability of
      occurrence", they have also been used for inference. However, this transformation
      can produce spurious results, and it must be used with caution. Here we study the
      statistical and ecological bases underlying the Beals smoothing function, and the
      factors that may affect the reliability of transformed values are explored using
      simulated data sets. Our simulations demonstrate that Beals predictions are
      unreliable for target species that are not related to the overall ecological
      structure. Furthermore, the presence of these "random" species may diminish the
      quality of Beals smoothing values for the remaining species. A statistical test
      is proposed to determine when observed values can be replaced with Beals
      smoothing predictions. Two real-data example applications are presented to
      illustrate the potentially false predictions of Beals smoothing and the necessary
      checking step performed by the new test.

PMID- 18343954
TI  - Linking nitrogen partitioning and species abundance to invasion resistance in the
      Great Basin.
AB  - Resource partitioning has been suggested as an important mechanism of invasion
      resistance. The relative importance of resource partitioning for invasion
      resistance, however, may depend on how species abundance is distributed in the
      plant community. This study had two objectives. First, we quantified the degree
      to which one resource, nitrogen (N), is partitioned by time, depth and chemical
      form among coexisting species from different functional groups by injecting (15)N
      into soils around the study species three times during the growing season, at two
      soil depths and as two chemical forms. A watering treatment also was applied to
      evaluate the impact of soil water content on N partitioning. Second, we examined
      the degree to which native functional groups contributed to invasion resistance
      by seeding a non-native annual grass into plots where bunchgrasses, perennial
      forbs or annual forbs had been removed. Bunchgrasses and forbs differed in
      timing, depth and chemical form of N capture, and these patterns of N
      partitioning were not affected by soil water content. However, when we
      incorporated abundance (biomass) with these relative measures of N capture to
      determine N sequestration by the community there was no evidence suggesting that
      functional groups partitioned different soil N pools. Instead, dominant
      bunchgrasses acquired the most N from all soil N pools. Consistent with these
      findings we also found that bunchgrasses were the only functional group that
      inhibited annual grass establishment. At natural levels of species abundance, N
      partitioning may facilitate coexistence but may not necessarily contribute to N
      sequestration and invasion resistance by the plant community. This suggests that
      a general mechanism of invasion resistance may not be expected across systems.
      Instead, the key mechanism of invasion resistance within a system may depend on
      trait variation among coexisting species and on how species abundance is
      distributed in the system.

PMID- 18343955
TI  - Response to prednisone in relation to NR3C1 intron B polymorphisms in childhood
      nephrotic syndrome.
AB  - The variation in time required to obtain cessation of proteinuria in children
      with nephrotic syndrome (NS) represents one aspect of the variations shown by
      these children in response to glucocorticoid (GC) treatment. Polymorphism of the
      GC receptor gene (NR3C1) has been postulated as one factor that would partially
      explain differences in both the clinical presentation and the reaction to
      treatment in GC-treated diseases. We genotyped 118 children diagnosed with NS who
      initially responded to oral GC treatment [steroid-responsive nephrotic syndrome
      (SRNS) group] and 136 healthy children for three intron B single nucleotide
      polymorphisms of NR3C1, namely Bcl I (C/G), rs33389 (C/T) and rs33388 (A/T). In
      the SRNS group, we performed a three-marker haplotype analysis of NR3C1 in
      relation to the response to prednisone, represented as time to proteinuria
      resolution (TPR) as categorical and ordinal variable. RESULTS: The distribution
      of individual polymorphisms and three-marker haplotypes was similar in healthy
      children and SRNS patients (all p values >0.05). The GTA haplotype was associated
      with a higher GC sensitivity, as determined by TPR, and was found to be more
      prevalent in early (response <or=7 days) than late (response >7 days) prednisone
      responders (27.7 vs. 14.5%, hap-score = -2.22, p = 0.05 adjusted for biopsy
      results). These results are in agreement with those reported earlier on an
      association of intron B haplotypes with GC sensitivity. The distribution of GC
      polymorphisms among the residents of north-eastern Poland was also determined.

PMID- 18343956
TI  - The use of ocular abnormalities to diagnose X-linked Alport syndrome in children.
AB  - The diagnosis of X-linked Alport syndrome is often difficult, but the
      demonstration of lenticonus and retinopathy may facilitate the diagnosis in adult
      patients. The aim of this study was to determine the diagnostic usefulness of
      ocular examination in children. Fourteen families with at least one affected
      child were studied clinically, and COL4A5 mutations were determined. The families
      included 15 affected boys (median age 11 years, range 4-19 years). Two boys (13%)
      had renal failure, nine (60%) had a known hearing loss, one (7%) had lenticonus
      and five (33%) had a central (4/15, 27%) or peripheral (4/14, 29%) retinopathy.
      Lenticonus and retinopathy were first noted in 14 and 11 year olds, respectively.
      All boys with retinopathy had a hearing loss. The early onset retinopathy was
      associated with a severe mutation (Q1383X). Eight families (8/14, 57%) comprised
      only sons and mothers, and two mothers (2/12, 17%) had the retinopathy. Six boys
      (40%) would have been diagnosed with Alport syndrome on the basis of their own or
      their mother's ocular examinations. None of the six girls (median age 8 years,
      range 7-14 years) had ocular abnormalities. Hearing loss is usually highly
      sensitive for the diagnosis of Alport syndrome, but ocular examination of boys
      and their mothers at the initial consultation is a non-invasive test that is
      helpful in up to 40% cases.

PMID- 18343957
TI  - Simple technique for removing broken pedicular screw with plain and serviceable
      screwdriver.
AB  - Removing the broken pedicular screw after spinal hardware failure is usually
      problematic. A specially designed simple screwdriver and easy removal technique
      of broken pedicular screw with this screwdriver are described in this article.

PMID- 18343958
TI  - Modeling mucosal dimensions after implantation of a bio-absorbable membrane for
      surgical root coverage.
AB  - The aim of this study was to model alterations of mucosal thickness after
      implantation of a bio-absorbable membrane for surgical root coverage employing
      guided tissue regeneration. Periodontal conditions around 31 recession sites in
      14 patients were assessed for up to 12 months after surgery. Mucosal thickness
      was modeled in a multivariate, three-level (occasion, tooth, subject) time series
      model. The amount of root coverage was studied in a bivariate multilevel model of
      change and mean recession to avoid mathematic coupling. Predictions of gingival
      thickness were, at the outset, strongly related to baseline gingival width. At
      maxillary teeth, gingival thickness at all measurement locations peaked 3 months
      after surgery with negative relations to baseline gingival width. Thereafter,
      thickness gradually decreased but remained higher (0.3-0.5 mm, 95% confidence
      interval 0.05-0.9 mm) than before surgery, while positive correlations with
      baseline gingival width were re-established. At mandibular teeth, gingival
      thickness did not change so dramatically, while thickness of lining mucosa
      underwent similar changes as at maxillary teeth. In contrast to previous
      publications, modeling change of recession depth and mean recession did not yield
      better results in deeper sites when applying a bivariate multilevel model that
      avoids mathematic coupling.

PMID- 18343959
TI  - The decomposition of alpha-aminophosphine oxides to phosphonic acid derivatives
      (PIII).
AB  - Aminophosphine oxides and aminophosphonates are, in general, very stable
      compounds. However, following phosphorus-carbon bond cleavage in aqueous acidic
      media these compounds sometimes decompose to phosphonic acids derivatives
      (P(III)). Despite some controversy in the literature, careful analysis supported
      by theoretical studies leads to the conclusion that decomposition to P(III)
      derivatives proceeds via an elimination reaction.

PMID- 18343960
TI  - Molecular modeling and dynamics studies of cytidylate kinase from Mycobacterium
      tuberculosis H37Rv.
AB  - Bacterial cytidylate kinase or cytidine monophosphate kinase (CMP kinase)
      catalyses the phosphoryl transfer from ATP to CMP and dCMP, resulting in the
      formation nucleoside diphosphates. In eukaryotes, CMP/UMP kinase catalyses the
      conversion of UMP and CMP to, respectively, UDP and CDP with high efficiency.
      This work describes for the first time a model of bacterial cytidylate kinase or
      cytidine monophosphate kinase (CMP kinase) from mycobacterium tuberculosis
      (MtCMPK). We modeled MtPCMPK in apo form and in complex with cytidine 5'
      monophosphate (CMP) to try to determine the structural basis for specificity.
      Comparative analysis of the model of MtCMPK allowed identification of structural
      features responsible for ligand affinities. Analysis of the molecular dynamics
      simulations of these two systems indicates the structural features responsible
      for the stability of the structure, and may help in the identification of new
      inhibitors for this enzyme.

PMID- 18343961
TI  - Theoretical study of the novel sandwich compound [Au3Cl3Tr 2]2+.
AB  - A theoretical study of a sandwich compound with a metal monolayer sheet between
      two aromatic ligands is presented. A full geometry optimization of the
      [Au(3)Cl(3)Tr(2)](2+) (1) compound, which is a triangular gold(I) monolayer sheet
      capped by chlorines and bounded to two cycloheptatrienyl (Tr) ligands was carried
      out using perturbation theory at the MP2 computational level and DFT. Compound
      (1) is in agreement with the 18-electron rule, the bonding nature in the complex
      may be interpreted from the donation interaction coming from the Tr rings to the
      Au array, and from the back-donation from the latter to the former. NICS
      calculations show a strong aromatic character in the gold monolayer sheet and Tr
      ligands; calculations done with HOMA, also report the same aromatic behavior on
      the cycloheptatrienyl fragments giving us an insight on the stability of (1). The
      Au -Au bond lengths indicate that an intramolecular aurophilic interaction among
      the Au(I) cations plays an important role in the bonding of the central metal
      sheet.

PMID- 18343962
TI  - Characterization of a complete cycle of acetylcholinesterase catalysis by ab
      initio QM/MM modeling.
AB  - The reaction mechanism of acetylcholine hydrolysis by acetylcholinesterase,
      including both acylation and deacylation stages from the enzyme-substrate (ES) to
      the enzyme-product (EP) molecular complexes, is examined by using an ab initio
      type quantum mechanical - molecular mechanical (QM/MM) approach. The density
      functional theory PBE0/aug-6-31+G* method for a fairly large quantum part trapped
      inside the native protein environment, and the AMBER force field parameters in
      the molecular mechanical part are employed in computations. All reaction steps,
      including the formation of the first tetrahedral intermediate (TI1), the
      acylenzyme (EA) complex, the second tetrahedral intermediate (TI2), and the EP
      complex, are modeled at the same theoretical level. In agreement with the
      experimental rate constants, the estimated activation energy barrier of the
      deacylation stage is slightly higher than that for the acylation phase. The
      critical role of the non-triad Glu202 amino acid residue in orienting lytic water
      molecule and in stabilizing the second tetrahedral intermediate at the
      deacylation stage of the enzymatic process is demonstrated.

PMID- 18343963
TI  - A bone remodelling model including the directional activity of BMUs.
AB  - Bone is able to adapt itself to the mechanical and biological environment by
      changing its porosity and/or orientation of its internal microstructure in a
      process known as bone remodelling. As a consequence, a change of bone mechanical
      properties is produced leading to an optimum structure, able to bear the external
      loads with the minimum weight. This adaptation is carried out by a temporal
      association of cells known as BMUs (basic multicellular units) that resorb old
      bone and sometimes produce new organic extracellular matrix (osteoid) that is
      later mineralized. This involves changes in porosity, damage level (density of
      microcracks accumulated by cyclic loads) and mineral content. All of these
      features were taken into account in a previous model, but the whole process and
      therefore the resulting bone constitutive behaviour was considered isotropic. The
      model proposed herein, recognizing that bone is actually anisotropic, tries to
      explain how BMUs modify the anisotropy by changing their progressing direction.
      We check the potential of the model to predict the alignment of the bone
      microstructure with the external loads in different situations. Then, the model
      is also applied to obtain the anisotropy and mechanical properties of the human
      proximal femur under physiological loads with initial conditions corresponding to
      a heterogeneous, but otherwise isotropic bone.

PMID- 18343964
TI  - Electroretinographic study of spontaneously diabetic Torii rats.
AB  - Spontaneously diabetic Torii (SDT) rats are an inbred strain of rats with a non
      obese type 2 diabetes mellitus that were isolated from an outbred colony of
      Sprague-Dawley (SD) rats. Electroretinograms (ERGs) were recorded from SDT and SD
      (controls) rats at 10- and 44-weeks-of-age to determine their retinal function.
      The amplitudes and implicit times of the ERGs of the right and left eyes were not
      significantly different indicating that the intra-individual variation was small.
      Both amplitudes and implicit times of the ERGs in the SDT rats were not
      significantly different from those of SD rats at 10-weeks-of-age. At 44-weeks-of
      age, however, the a- and b-waves and the oscillatory potentials were
      significantly reduced with prolonged implicit times in the SDT rats compared to
      SD rats. These depressed ERGs may reflect vascular and neuronal damage throughout
      the retina as are seen in the advanced stages of human diabetic retinopathy.
      Thus, the SDT rat can be used to study the retinal physiology of diabetic
      retinopathy.

PMID- 18343965
TI  - Ventricular arrhythmias and changes in heart rate preceding ventricular
      tachycardia in patients with an implantable cardioverter defibrillator.
AB  - The objective was to determine the characteristics of heart rate variability and
      ventricular arrhythmias prior to the onset of ventricular tachycardia (VT) in
      patients with an implantable cardioverter defibrillator (ICD). Sixty-eight beat
      to-beat time series from 13 patients with an ICD were analyzed to quantify heart
      rate variability and ventricular arrhythmias. The episodes of VT were classified
      in one of two groups depending on whether the sinus rate in the 1 min preceding
      the VT was greater or less than 90 beats per minute. In a subset of patients,
      increased heart rate and reduced heart rate variability was often observed up to
      20 min prior to the VT. There was a non-significant trend to higher incidence of
      premature ventricular complexes (PVCs) before VT compared to control recordings.
      The patterns of the ventricular arrhythmias were highly heterogeneous among
      different patients and even within the same patient. Analysis of the changes of
      heart rate and heart rate variability may have predictive value about the onset
      of VT in selected patients. The patterns of ventricular arrhythmia could not be
      used to predict onset of VT in this group of patients.

PMID- 18343966
TI  - Elucidating risk mechanisms of gene-environment interactions on pediatric
      anxiety: integrating findings from neuroscience.
AB  - Recent findings of gene-environment interaction on child and adolescent anxiety
      generate interest in mechanisms through which genetic risks are expressed.
      Current findings from neuroscience suggest avenues for exploring putative
      mechanisms. Specifically recent documentations of abnormality in brain function
      among anxious adolescents may reflect the end-result of gene expression. In turn
      these inherited predispositions may increase the likelihood of psychopathology in
      the presence of stress. The aim of the current article is to consider putative
      mechanisms reflecting genetic sensitivity to the environment (G x E). Thus we
      review data implicating biased processing of threat information and anomalies in
      brain circuitry in the expression of pediatric anxiety. These data suggest that
      links across development among genes, brain, psychological processes, and
      behavior are far from established. Accordingly, the article proposes strategies
      for examining these links. Exploring these relationships during development is
      crucial, given that these early life processes may potentially shape longer-term
      patterns of emotional behavior, and therefore life-long trajectories of anxiety.

PMID- 18343967
TI  - The impact of subthalamic deep brain stimulation on bradykinesia of proximal and
      distal upper limb muscles in Parkinson's disease.
AB  - OBJECTIVE: To assess the differential effects of bilateral deep brain stimulation
      of the subthalamic nucleus on proximal and distal muscle groups of the upper limb
      in Parkinson's disease. METHODS: Eight parkinsonian subjects with chronic
      bilateral stimulation of the subthalamic nucleus performed index finger tapping
      (differentially drawing upon distal arm muscles), horizontal pointing
      (differentially drawing upon proximal arm muscles) and a complex reach-to-grasp
      task with cubes of different sizes, which involved both proximal and distal arm
      muscles. An ultrasound based system was used for kinematic motion analysis.
      Subjects were investigated in two clinical conditions: on and off subthalamic
      nucleus stimulation. Clinical symptom severity was rated with the Unified
      Parkinson's Disease Rating Scale (UPDRS) motor subscore. RESULTS: Stimulation of
      the subthalamic nucleus improved the UPDRS motor subscore (68 %). Bradykinesia of
      index finger tapping and horizontal pointing were equally improved by subthalamic
      nucleus stimulation. In contrast, in a complex reach-to-grasp task bradykinesia
      was differentially ameliorated for the grasp component. CONCLUSION: The data
      suggest that bilateral stimulation of the subthalamic nucleus improves
      bradykinesia of both distal and proximal muscles of the arm and hand in
      Parkinson's disease; however, dependent upon task complexity proximal and distal
      movement components may be affected differentially. Kinematic motion analysis is
      an efficient tool to objectively evaluate the beneficial effects of subthalamic
      nucleus stimulation on dexterity in Parkinson's disease.

PMID- 18343968
TI  - Heart failure in acute ischemic stroke.
AB  - BACKGROUND: To determine the impact of heart failure (HF), with preserved or
      decreased left ventricular function (LVF), on outcome in patients with acute
      ischemic stroke (AIS). METHODS: We studied 503 unselected ischemic stroke
      patients. Poor outcome was defined as moderate-severe disability or death at 90
      days. We analyzed the association between poor outcome and HF with preserved LVF
      or decreased LVF (systolic HF: ejection fraction lower than 50%). We tested this
      association adjusted by possible confounders in a logistic regression model.
      RESULTS: 89 patients (17.7 %) had HF; 49 patients (9.7%) with systolic HF, and 40
      (8%) patients with HF and preserved LVF. HF with preserved LVF patients were
      older [79.4 (7.9) vs. 74.3 (10.4), p = 0.013],more likely to be women [p <
      0.001,OR = 8.61, 95% CI (3.3-22.6)], and with lower current smoking habits [p =
      0.018, OR = 8.77 (1.1-72.6)] than patients with systolic HF. 151 patients (30 %)
      had poor outcome. We found an independent association with initial stroke
      severity, systolic HF (adjusted OR = 3.01), HF with preserved LVF (adjusted OR =
      2.52), thrombolytic treatment, statin pre-treatment (as protectors) and poor
      outcome. CONCLUSION: Both forms of HF (with or without decreased systolic
      function) are associated with poor outcome in AIS.

PMID- 18343969
TI  - A longitudinal study of olfactory function in patients with idiopathic
      Parkinson's disease.
AB  - Olfactory function is diminished in patients with idiopathic Parkinson disease
      (IPD). Because previous work almost exclusively relied upon cross-sectional
      studies, the present investigation aimed to address the correlation between
      olfactory loss and duration of disease within the context of a longitudinal
      study, accompanying well-diagnosed patients over an average period of 4.4 years.
      A group of 27 IPD patients was examined (5 women, 22 men; age range 27-64 years;
      duration of disease: 0 to 19 years). Psychophysical olfactory testing was
      performed after 3-6 years (mean 4.4 years) using the "Sniffin' Sticks" test
      battery which consists of subtests for odor thresholds, odor discrimination, and
      odor identification. The study yielded the following major results: (1) olfactory
      function in IPD patients changes in an unpredictable manner, (2) especially when
      considering results from the second session relatively few IPD patients were
      completely anosmic; none of the patients, however, were normosmic. One possible
      explanation for these findings may lie in the hypothesis based on results by
      Huisman et al. (2004) who reported an increase of dopaminergic neurons in the
      olfactory bulb in IPD patients. In this scenario, olfactory loss seen early in
      the disease may be based on an incomplete inhibition of olfactory input at the
      level of the olfactory bulb.

PMID- 18343970
TI  - Electronic colon-cleansing for CT colonography: diagnostic performance.
AB  - BACKGROUND: The purpose of this study was to evaluate whether an electronic
      colonic-cleansing (ECC) algorithm is beneficial for the diagnostic performance
      compared to a CT colonography (CTC) evaluation without electronic cleansing in
      tagged datasets. METHODS: Two blinded readers evaluated CTC datasets from 79
      patients with 153 colorectal polyps confirmed by optical colonoscopy. Cases were
      read in a randomized order with and without the use of electronic colon-cleansing
      software. Per-polyp sensitivity, per-polyp/per-patient specificity and reading
      times (with and without ECC) have been calculated and reported. RESULTS: Per
      polyp sensitivity for polyps >6 mm without using ECC was 60.4% (Reader 1: 59.7%,
      Reader 2: 61.1%), while polyps >10 mm were detected with a sensitivity of 58.3%
      (Reader 1: 66.7%, Reader 2: 50%). On electronically cleansed datasets, the
      sensitivity was 73.6% (Reader 1: 76.4%; Reader 2: 70.8%) for polyps >6 mm and
      83.3% (Reader 1: 83.3%; Reader 2: 83.3%), respectively. Per-patient specificity
      was 75% without using cleansing (Reader 1: 68%, Reader 2: 82%) and 81.5% using
      ECC (Reader 1: 86%, Reader 2: 77%). CONCLUSION: Reading CTC cases using ECC
      software improves sensitivity in detecting clinically relevant colorectal polyps.

PMID- 18343971
TI  - Long-term outcome of a cuffed expanded PTFE graft for hemodialysis vascular
      access.
AB  - BACKGROUND: Development of venous outflow stenosis has been a major obstacle in
      maintaining the patency of dialysis vascular grafts. In the present study, we
      retrospectively analyzed the long-term results of cuffed expanded
      polytetrafluoroethylene (ePTFE) and non-cuffed (standard) ePTFE grafts placed for
      hemodialysis access. MATERIALS AND METHODS: A total of 67 patients who underwent
      placement of either cuffed (n = 41) or standard (n = 26) ePTFE grafts were
      retrospectively analyzed. There were no significant differences between the two
      groups with regard to age, gender, cause of end-stage renal disease, and anatomic
      placement of the graft. Endpoints consisted of primary (without any intervention)
      and secondary (with radiological or surgical intervention) graft patency rates at
      1-3 years. RESULTS: There was a trend toward better primary graft patency rates
      in the cuffed versus the standard ePTFE: 37.7% vs. 25.7% at 1 year, 35% vs. 10.3%
      at 2 years, 28% vs. 5.1% at 3 years, respectively (p = 0.086, Kaplan-Meier).
      Secondary patency rates in the cuffed group were significantly superior (p =
      0.047) to those in the standard group (81.8% vs. 56.1% at 1 year, 61.8% vs. 46.3%
      at 2 years, 51.5% vs. 33.1% at 3 years, respectively). Thrombosis as a cause of
      complete graft failure was significantly higher (34%) in the standard group than
      in the cuffed group (9%) (p = 0.0125). CONCLUSIONS: Compared to the standard
      ePTFE, the cuffed ePTFE graft provided better long-term outcome, especially in
      terms of secondary patency rates after radiological intervention.

PMID- 18343972
TI  - Retroperitoneoscopic adrenalectomy in Conn's syndrome caused by adrenal adenomas
      or nodular hyperplasia.
AB  - BACKGROUND: In patients with primary hyperaldosteronism, solitary adrenal
      adenomas are an indication for surgical intervention. In contrast, adrenal
      hyperplasia is almost exclusively treated by drugs. PATIENTS AND METHODS: In a
      prospective clinical study 183 patients (81 men, 102 women; age 49.6+/-12.8
      years) with Conn's syndrome were operated on using the posterior
      retroperitoneoscopic approach. Tumor size ranged from 0.2 to 5.0 cm (mean 1.5+/
      0.8 cm). Final histology described a solitary adenoma in 127 patients and adrenal
      hyperplasia in 56 patients. Partial adrenalectomies were performed in 47
      operations. RESULTS: The perioperative complication rate was 4%, mortality zero.
      In none of the cases was conversion to open surgery necessary. The mean operating
      time was 58+/-32 minutes (range 20-230 minutes) and was associated with sex
      (p<0.001) but not with the extent of resection (partial vs. total, p=0.51) or
      with tumor size (<or=1.5 vs. >1.5 cm; p=0.43) or tumor site (p=0.77). Median
      blood loss was 15 ml. Median duration of postoperative hospitalization was 4
      days. After a mean follow-up of nearly 5 years, 96% of patients are normokalemic,
      30% of patients are cured (normotensive without medication), and 87% showed an
      improvement of hypertension (normotensive without or with reduced medication).
      Cure of hypertension depended on the patient's age (p<0.001) and sex (p<0.001),
      duration of hypertension (p<0.05), and histomorphology (p<0.001). Improvement of
      hypertension was not associated with any of these factors. CONCLUSIONS:
      Retroperitoneoscopic removal of adrenal glands in patients with Conn's syndrome
      is a safe, rapidly performed surgical procedure and can thus be considered as
      first choice option for treatment of both solitary adrenal adenomas and
      hyperplasia presenting with a clinically predominating nodule.

PMID- 18343973
TI  - Prognostic models for predicting death after hepatectomy in individuals with
      hepatic metastases from colorectal cancer.

PMID- 18343974
TI  - Surgical training in the Netherlands.
AB  - Surgical training in the Netherlands has traditionally been characterized by
      learning on the job under the classic master-trainee doctrine. Over the past
      decades, it has become regionally organized with intensive structural training
      courses, and a peer-based quality control system. Recently, the nationwide
      programme has been modernized further and now involves a systematic, competency
      based education with structural training courses, formalized assessment and room
      for reflection by residents under the supervision of surgical teaching groups. To
      this end, a uniform web-based digital portfolio is being introduced to facilitate
      monitoring of the individual resident's progress. Though requiring inspirational
      leadership, commitment, and determination, this modernization has sparked
      enthusiasm among trainees and teachers.

PMID- 18343975
TI  - Tom1l2 hypomorphic mice exhibit increased incidence of infections and tumors and
      abnormal immunologic response.
AB  - Studies have shown that the TOM1 family of proteins, including TOM1 and TOM1L1,
      are actively involved in endosomal trafficking and function in the immune
      response. However, much less is known about the function of TOM1L2. To understand
      the biological importance of TOM1L2 and the potential significance of its
      cellular role, we created and evaluated Tom1l2 gene-trapped mice with reduced
      Tom1l2 expression. Mice hypomorphic for Tom1l2 exhibited numerous infections and
      tumors compared to wild-type littermates. Associated with this increased risk for
      infection and tumor formation, apparently healthy Tom1l2 hypomorphs also had
      splenomegaly, elevated B- and T-cell counts, and an impaired humoral response,
      although at a reduced penetrance. Furthermore, cellular localization studies
      showed that a Tom1l2-GFP fusion protein colocalizes with Golgi compartments,
      supporting the role of Tom1l2 in cellular trafficking, while molecular modeling
      and bioinformatic analysis of Tom1l2 illustrated a structural basis for a
      functional role in trafficking. These results indicate a role for Tom1l2 in the
      immune response and possibly in tumor suppression.

PMID- 18343976
TI  - A floral-derived compound attractive to the tephritid fruit fly parasitoid
      Diachasmimorpha longicaudata (Hymenoptera: Braconidae).
AB  - Many adult hymenopteran parasitoids, even host-feeding species, consume the
      nectar of flowering plants. Previous field studies had identified plants
      attractive (Lobularia maritima L.) and unattractive (Spermacoce verticillata L)
      to certain opiine braconids (Hymenoptera). Under laboratory conditions,
      Diachasmimorpha longicaudata (Ashmead), a parasitoid of tephritid fruit fly
      larvae and representative opiine, responded in flight tunnels to L. maritima but
      not to S. verticillata. Volatile chemicals of the two flowers were collected and
      analyzed by using capillary gas liquid chromatography and mass spectral analysis.
      Acetophenone was isolated from L. maritima but not from S. verticillata. In
      flight tunnels, D. longicaudata were exposed to 10 concentrations (doses) of
      acetophenone. Female parasitoids showed a significant attraction to several
      acetophenone doses, with concentrations of 25 and 50 ng the most attractive. No
      odor source, either floral or floral-derived, was attractive to male parasitoids.
      Reliable trapping systems for parasitoid species, particularly species such as D.
      longicaudata used for augmentative biological control, would be a valuable
      monitoring tool. At present, there are few, if any, florally derived synthetic
      lures for attracting hymenopteran parasitoids.

PMID- 18343977
TI  - Laparoscopic sleeve gastrectomy as an alternative to gastric bypass in patients
      with multiple intraabdominal adhesions.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy and its indications are currently
      being evaluated. The objective of this study was to show the preliminary results
      obtained with this technique indicated as an alternative to gastric bypass in
      patients with multiple intraabdominal adhesions, therefore preserving the
      benefits of the laparoscopic approach. METHODS: An analysis of all patients who
      underwent a laparoscopic sleeve gastrectomy for the above indication was done.
      Data included demographics, number of previous surgeries, operative time,
      morbidity, mortality, and %EWL at 3 and 6 months. RESULTS: Fifteen patients
      underwent laparoscopic sleeve gastrectomy as an alternative to gastric bypass
      because of multiple intraabdominal adhesions. No patient required conversion to
      an open procedure; morbidity was 6% with no mortality. %EWL at 3 months was 41%
      and at 6 months was 44%. Mean follow-up was 6 months. CONCLUSION: In our initial
      experience, laparoscopic sleeve gastrectomy proved to be a safe and effective
      alternative to gastric bypass for patients with multiple intraabdominal
      adhesions.

PMID- 18343978
TI  - A comparison of eating disorders among patients receiving surgical vs non
      surgical weight-loss treatments.
AB  - BACKGROUND: Little is known about differences between patients in surgical and
      non-surgical weight-loss treatments (WLT) regarding eating disorders, level of
      general psychopathology, and health-related quality of life (HRQL). Such
      differences could indicate different clinical needs in the management of surgical
      compared to non-surgical WLT patients. METHODS: Participants were a subset of 100
      patients from a Swedish study investigating the long-term effects of eating
      disorders in WLT. Participants filled out the Eating Disorders in Obesity
      Questionnaire as well as self-rating questionnaires of general psychopathology
      and HRQL before initiating surgical (n = 54) or non-surgical (n = 46) WLT.
      RESULTS: Eating disorders were found to be more common among patients accepted
      for surgical treatments, whereas binge eating (as a symptom) was found to be
      equally common in both groups. Surgical patients also indicated higher levels of
      psychopathology compared to those receiving non-surgical treatment. CONCLUSION:
      Patients in surgical WLT are younger, more obese, and indicate higher levels of
      eating disorders and psychopathology than non-surgical WLT patients. Results
      highlight the importance of surgical WLT units having adequate knowledge,
      resources, and methods for detecting and addressing issues of eating disorders
      and psychopathology before and during the WLT. Future longitudinal studies need
      to ascertain to what extent eating and general psychopathology influence the
      outcome of WLT in terms of lapses, complications, weight gain, quality of life,
      etc.

PMID- 18343979
TI  - Small stem total hip arthroplasty in hypoplasia of the femur.
AB  - Total hip arthroplasty in hypoplastic femurs is technically difficult and the
      incidence of complications and aseptic loosening is relatively high. Cemented,
      uncemented, off-the-shelf, and custom-made stems all have been advocated in these
      cases. From 1978 to 1997, we performed 86 total hip arthroplasties in 77 patients
      with a hypoplastic femur using a cemented, off-the-shelf, small, curved, cobalt
      chromium stem. We hypothesized results equaled those of the identical but larger
      sized stems in normal-sized femora which were used as comparisons. Clinical and
      radiographic evaluations were performed. Minimum followup was 4.2 years (mean, 12
      years; range, 4.2-20.3 years); mean Harris hip score was 88, and mean hip flexion
      was 104 degrees . Six stems were revised: four because of aseptic loosening, one
      after a femoral fracture, and one because of malpositioning. Complications
      included one perforation and one fracture of the femur, one fracture, one
      nonunion of the greater trochanter, and one deep infection. Implant survivorship
      for all hips at 15 years with aseptic revision of the stem as the end point was
      90% (confidence interval, 82-99) which equaled results of the larger stems. The
      small off-the-shelf cemented Weber stem has a high long-term survival and a low
      complication rate. Survival compares favorably with other small-sized total hip
      systems. LEVEL OF EVIDENCE: Level III, therapeutic study, case-control.

PMID- 18343980
TI  - Operative treatment of interdigital Morton's neuroma.
AB  - The Authors present their experience in the surgical treatment of Morton's
      neuroma via a dorsal approach. The assessed results have been very good in terms
      of a clear clinical improvement and no recurrences in all the treated cases. The
      histological examination carried out on all the removed samples have shown that
      the thickening of the nerve first occurs due to perineural fibrosis and
      successively associated with sclerohyalinosis of the tissue, which is in line
      with the already existing literature reports. The Authors of the article reckon
      the adopted surgical technique to be simple, safe and highly effective.

PMID- 18343981
TI  - Nora's lesion. Clinical and therapeutic considerations.
AB  - In this article we report a case of bizarre paraosteal osteochondromatous
      proliferation (BPOP), also known as Nora's lesion, arising on the distal phalanx
      of the fifth finger of the hand in a young-adult subject. In this paper, we
      discuss the possible therapeutic programme related to the grade of severity of
      the clinical features and underline the rarity of this lesion and the difficulty
      of diagnosis, which is exclusively histological.

PMID- 18343982
TI  - Myocardial ischemia and reperfusion injury in rats: lysosomal hydrolases and
      matrix metalloproteinases mediated cellular damage.
AB  - The aim of this study was to evaluate the time course events of cellular damage
      during myocardial ischemia and reperfusion injury in rats and to find out a
      correlation between the structural alterations with respect to the biochemical
      changes. Cardiac biomarkers and lysosomal enzymes viz. cathepsin D, acid
      phosphatase and beta-glucuronidase and matrix metalloproteinases (MMPs) were
      evaluated at different time points, in response to ischemia-reperfusion induced
      oxidative stress in an isolated rat heart model perfused in Langendorff mode.
      Microscopically, changes in myocardial architecture, myofibrillar degradation,
      and collagen (COL) integrity were studied using hematoxylin-eosin, Masson's
      trichrome and toluidine blue staining techniques. A three-fold increase in the
      level of myoglobin was observed after 30 min of ischemia followed by 120 min of
      reperfusion as compared to 15 min ischemia, 120 min reperfusion. Similarly, a
      significant increase (P<0.05) in the levels of lipid peroxides and superoxide
      anion coupled with a decrease in enzymatic and nonenzymatic antioxidant levels
      were observed. A concomitant increase in the activity of cathepsin D (24.07+/
      0.95) and a higher expression of MMPs after 120 min of reperfusion following 30
      min ischemia were shown to correlate with the myocardial damage as shown by
      histopathology, suggesting that free radical induced activation of cathepsin D
      and MMPs could mediate early damage during myocardial ischemia and reperfusion.

PMID- 18343983
TI  - A comparison between polymeric microsphere and bacterial vectors for macrophage
      P388D1 gene delivery.
AB  - PURPOSE: The purpose of this study was to compare bacterial and polymeric gene
      delivery devices for the ability to deliver plasmid DNA to a murine macrophage
      P388D1 cell line. METHODS: An 85:15 ratio of poly(lactic-co-glycolic acid) (PLGA)
      and poly(beta-amino ester) polymers were formulated into microspheres that
      physically entrapped plasmid DNA encoding for the firefly luciferase reporter
      gene; whereas, the same plasmid was biologically transformed into a strain of
      Escherichia coli engineered to produce recombinant listeriolysin O. The two
      delivery devices were then tested for gene delivery and dosage effects using a
      macrophage cell line with both assays taking advantage of a 96-well high
      throughput format to quantify and compare each vector type. RESULTS: Gene
      delivery was comparable for both vectors at higher vector dosages while lower
      dosages showed an improved delivery for the microsphere vectors. Delivery
      efficiency (defined as luciferase measurement/mg cellular protein/ng DNA
      delivered) was 881 luminescence mg(-1) ng(-1) for polymeric microspheres compared
      to 171 luminescence mg(-1) ng(-1) for the bacterial vectors. CONCLUSION: A first
      head-to-head comparison between polymeric and bacterial gene delivery vectors
      shows a delivery advantage for polymeric microspheres that must also be evaluated
      in light of vector production, storage, and future potential.

PMID- 18343984
TI  - Detection of infectious bursal disease virus (IBDV) genome in free-living pigeon
      and guinea fowl in Africa suggests involvement of wild birds in the epidemiology
      of IBDV.
AB  - Infectious bursal disease (IBD) virus (IBDV) serotype 1 is the causative agent of
      IBD, a highly contagious immunosuppressive disease of young chickens. In this
      study, we examined IBDV infection in apparently healthy 21 guinea fowls and 20
      pigeons obtained in Tanzania and Zambia by virus neutralization test (VNT) and
      reverse transcription polymerase chain reaction (RT-PCR) for the VP2
      hypervariable region (VP2-HVR) of IBDV. Two guinea fowls (9.5%) in Tanzania were
      RT-PCR and VNT positive for IBDV, and 1 pigeon (5%) in Tanzania was RT-PCR
      positive and VNT negative. Phylogenetic analysis based on the nucleotide
      sequences of the PCR products indicated that segment A of IBDV detected from one
      guinea fowl and a pigeon belonged to the very virulent genotype of European/Asian
      type, while the other IBDV detected from a guinea fowl belonged to the classical
      genotype. To our knowledge, this is the first report of detection of the IBDV
      genome in free-living pigeons and guinea fowls. The detection of IBDV from
      apparently healthy guinea fowls and pigeons elucidates the role of wild birds in
      the epidemiology of IBDV.

PMID- 18343985
TI  - Phylogenetic analysis of porcine circovirus type 2 (PCV2) pre- and post-epizootic
      postweaning multisystemic wasting syndrome (PMWS).
AB  - The porcine circovirus type 2 (PCV2) genome encodes three major open reading
      frames (ORFs) encoding the replicase proteins (ORF1), the viral capsid protein
      (ORF2), and a protein with suggested apoptotic activity (ORF3). Previous
      phylogenetic analyses of complete genome sequences of PCV2 from GenBank have
      demonstrated 95-100% intra-group nucleotide sequence identity. However, although
      these isolates were readily grouped into clusters and clades, there was no
      correlation between the occurrence of specific PCV2 genotypes and the geographic
      origin or health status of the pig. In the present study, a unique dataset from a
      field study spanning the years pre and post the recognition of postweaning
      multisystemic wasting syndrome (PMWS) in Sweden was utilized. Using this dataset
      it was possible to discriminate three Swedish genogroups (SG1-3) of PCV2, of
      which SG1 was recovered from a pig on a healthy farm ten years before the first
      diagnosis of PMWS in Sweden. The SG1 PCV2/ORF2 gene sequence has been
      demonstrated to exhibit a high genetic stability over time and has subsequently
      only been demonstrated in samples from pigs on nondiseased farms. In contrast,
      SG2 was almost exclusively found on farms that had only recently broken down with
      PMWS whereas the SG3 genogroup predominated in pigs from PMWS-affected farms.
      These results further support the results obtained from earlier in vitro and in
      vivo experimental models and suggest the association of specific PCV2 genogroups
      with diseased and nondiseased pigs in the field.

PMID- 18343986
TI  - Identification of putative endogenous retroviruses actively transcribed in the
      brain.
AB  - Remnant proviral sequences in the genome resulting from the ancient germline
      infection of exogenous retroviruses are called endogenous retroviruses (ERVs).
      The transcriptional activation of human ERVs (HERVs) in the brain of patients
      with some neurologic diseases suggests that ERVs may participate in certain
      disease processes in the central nervous system. In this study, we identified
      putative murine ERVs (MuERVs) which are transcriptionally active in the brain and
      characterized their biological properties to better understand the ERVs' roles in
      the brain pathophysiology. The brain and selective non-nervous tissues (heart,
      muscle, adrenal gland, and salivary gland) of female C57BL/6J mice were subjected
      to RT-PCR analyses of MuERV expression by amplifying the 3'-end U3 regions and
      full-length/subgenomic transcripts. The expression patterns of the U3 regions and
      subgenomic transcripts in the brain were unique compared to the other tissues as
      well as the genomic MuERV profile. Two putative MuERVs (8,027 and 5,668 bp) were
      mapped on the mouse genome (chromosome 10, and chromosomes 4 and 8, respectively)
      using the MuERV U3 sequences, which were evidently expressed in the brain, as
      probes. Biological properties of these putative MuERVs, such as transcription
      potential, primer binding site, coding potential, integration age, recombination,
      and flanking host genes, were characterized. In particular, one of the two
      putative MuERV isolates had coding potentials for intact group specific antigen
      (gag), and truncated polymerase (pol) and envelope (env) polypeptides, while the
      other was defective for all three polypeptides. The findings from this study
      suggest that a specific group of MuERVs are constitutively expressed in the brain
      and they may participate in normal and pathogenic events pertaining to the brain
      through their replication gene products (e.g., gag and env polypeptides) as well
      as interactions with flanking host genes.

PMID- 18343987
TI  - Sex differences in patterns of genital sexual arousal: measurement artifacts or
      true phenomena?
AB  - Sex differences in patterns of sexual arousal have been reported recently. Men's
      genital arousal is typically more category-specific than women's, such that men
      experience their greatest genital arousal to stimuli depicting their preferred
      sex partners whereas women experience significant genital arousal to stimuli
      depicting both their preferred and non-preferred sex partners. In addition, men's
      genital and subjective sexual arousal patterns are more concordant than women's:
      The correlation between genital and subjective sexual arousal is much larger in
      men than in women. These sex differences could be due to low response-specificity
      in the measurement of genital arousal in women. The most commonly used measure of
      female sexual arousal, vaginal photoplethysmography, has not been fully validated
      and may not measure sexual arousal specifically. A total of 20 men and 20 women
      were presented with various sexual and non-sexual emotionally laden short film
      clips while their genital and subjective sexual arousal were measured. Results
      suggest that vaginal photoplethysmography is a measure of sexual arousal
      exclusively. Women's genital responses were highest during sexual stimuli and
      absent during all non-sexual stimuli. Sex differences in degree of category
      specificity and concordance were replicated: Men's genital responses were more
      category-specific than women's and men's genital and subjective sexual arousal
      were more strongly correlated than women's. The results from the current study
      support the continued use of vaginal photoplethysmography in investigating sex
      differences in patterns of sexual arousal.

PMID- 18343988
TI  - Use of pornography in a random sample of Norwegian heterosexual couples.
AB  - This study examined the use of pornography in couple relationships to enhance the
      sex-life. The study contained a representative sample of 398 heterosexual couples
      aged 22-67 years. Data collection was carried out by self-administered postal
      questionnaires. The majority (77%) of the couples did not report any kind of
      pornography use to enhance the sex-life. In 15% of the couples, both had used
      pornography; in 3% of the couples, only the female partner had used pornography;
      and, in 5% of the couples, only the male partner had used pornography for this
      purpose. Based on the results of a discriminant function analysis, it is
      suggested that couples where one or both used pornography had a more permissive
      erotic climate compared to the couples who did not use pornography. In couples
      where only one partner used pornography, we found more problems related to
      arousal (male) and negative (female) self-perception. These findings could be of
      importance for clinicians who work with couples.

PMID- 18343989
TI  - Laboratory-induced hyperventilation differentiates female sexual arousal disorder
      subtypes.
AB  - The effects of heightened sympathetic nervous system (SNS) activity via
      laboratory-induced hyperventilation (LIH) on subjective and physiological sexual
      arousal were examined in a heterogeneous group of women with Sexual Arousal
      Disorder (SAD; n = 60), as well as across subtypes of SAD, in comparison to a
      control group of women without sexual difficulties (n = 42). Participants took
      part in 2 min of rapid breathing, a technique previously found to increase SNS
      activity, immediately prior to viewing erotic stimuli. Physiological arousal
      (i.e., vaginal pulse amplitude; VPA) was measured via the vaginal
      photoplethysmograph and subjective arousal was measured via self-report
      questionnaires. LIH differentiated women with SAD from those in the control
      group, with LIH increasing VPA in the latter, but having no significant effect in
      the heterogeneous SAD group. However, among subtypes of SAD, LIH differentiated
      women with genital (n = 16) and subjective (n = 16) subtypes of SAD from women
      with combined SAD (n = 28) and women without sexual difficulties. Specifically,
      women in the control group and those with combined SAD had a significant increase
      in VPA whereas women with genital or subjective SAD had a significant decrease in
      VPA following LIH. There was no significant effect of LIH on any self-report
      measure of sexual arousal following erotic stimuli. Implications of the results
      for the conceptualization, diagnosis, and treatment of SAD are discussed.

PMID- 18343990
TI  - Enhancing the net benefits of disseminating efficacious prevention programs: a
      note on target efficiency with illustrative examples.
AB  - We consider the implementation, in a non-research setting, of a new prevention
      program that has previously been evaluated in a randomized trial. When the target
      population for the implementation is heterogeneous, the overall net benefits of
      the implementation may differ substantially from those reported in the economic
      evaluation of the randomized trial, and from those that would be realized if the
      program were implemented within a selected subgroup of the target population.
      This note illustrates a simple and practical approach to targeting that can
      combine risk-factor results from the literature with the overall cost-benefit
      results from the program's randomized trial to maximize the expected net benefit
      of implementing the program in a heterogeneous population.

PMID- 18343991
TI  - Comparative proteomics analysis of cerebrospinal fluid of patients with Guillain
      Barre syndrome.
AB  - To better understand the pathophysiologic mechanisms underlying Guillain-Barre
      syndrome (GBS), Comparative proteomic analysis of cerebrospinal fluid (CSF)
      between patients with GBS (the experiment group) and control subjects suffering
      from other neurological disorders (the control group) was carried out using two
      dimensional gel electrophoresis (2-DE) technique, in combination with matrix
      assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF
      MS) and database searching to determine abnormal CSF proteins in GBS patients.
      Image analysis of 2-DE gels silver stained revealed that 10 protein spots showed
      significant differential expression between the two groups of CSF samples. The
      expression of cystatin C, transthyretin, apolipoprotein E and heat shock protein
      70 were decreased. However, haptoglobin, alpha-1-antitrypsin, apolipoprotein A-IV
      and neurofilaments were elevated. The subsequent ELISA measured the concentration
      of cystatin C and confirmed the result of the proteomic analysis. These
      identified proteins may be involved in the pathophysiological process of GBS and
      call for further studying the role of these proteins in the pathogenesis of the
      disease.

PMID- 18343992
TI  - N-acetylglucosaminyltransferase V modifies TrKA protein, regulates the receptor
      function.
AB  - 1. N-Acetylglucosaminyltransferases V (GnT-V/Mgat5) play a pivotal role in the
      processing of N-linked glycoproteins in the Golgi apparatus. The aim of the
      present study is to investigate whether the N-acetylglucosaminyltransferase V is
      able to modify TrKA, the high-affinity tyrosine kinase-type receptor for NGF, and
      thereby to regulate the receptor function. 2. Plasmids of the pcDNA3/GnT-V and
      pcDNA3 were transfected into PC12 cells. Expression of GnT-V protein was detected
      by Western blot. TrKA protein was examined by immunoprecipitation. Endocytosis of
      TrKA was investigated by the method of receptor internalization. 3. We report
      here that over-expression GnT-V directly modifies TrKA protein, accompanied by
      marked enhancement of axon outgrowth in rat pheochromocytoma cells (PC12)
      elicited by a low dose of NGF that alone is insufficient to induce neuronal
      differentiation. Further study indicated that modification of TrKA glycoprotein
      could directly enhance NGF-activated autophosphorylation of immunoprecipitated
      TrKA in vitro. To further elucidate the mechanism, we study the different time
      point of endocytosis of TrKA receptor. The results show that TrKA of GnT-V gene
      transfected PC12 Cells delayed their removal by constitutive endocytosis as
      compared to the mock cells, suggesting high expression of GnT-V may affect their
      receptor TrKA endocytosis. 4. These results strongly suggest that N
      acetylglucosaminyltransferase V functioning as a specific endogenous role of NGF
      receptor function, which appear to be due, at least in part, to the promotion of
      differentiation. This work is an important step toward intriguing innovative
      therapeutic strategies targeting glycosyltransferase.

PMID- 18343993
TI  - Life-threatening interstitial lung disease associated with trastuzumab: case
      report.
AB  - A female patient with HER2 positive, metastatic breast cancer presented with
      pulmonary infiltrates, and a plural effusion dyspnoea after several months of
      trastuzumab treatment. She had been treated without complications with six
      courses of docetaxel and trastuzumab in combination with dexamethasone with
      partial remission of disease. Malignancy, infection and cardiomyopathy were
      excluded as causes of dyspnoea. Pleural and broncheoalveolar fluid analyses (BAL)
      showed eosinophils. A diagnosis of trastuzumab-induced pneumonitis was made.
      After treatment with steroids there was gradual clinical improvement and
      disappearance of infiltrates. Although a causative association between
      trastuzumab and this patient's pulmonary syndrome was not proven, the potential
      for this toxicity should be considered.

PMID- 18343994
TI  - Models for predicting BRCA1 and BRCA2 mutations in Han Chinese familial breast
      and/or ovarian cancer patients.
AB  - PURPOSE: Our aim was to find an appropriate method to estimate the likelihood
      that a family history of cancer was a result of a mutation in the BRCA1 or BRCA2
      genes. We also compared the performance of the established method with three
      different methods (Couch, Sh-E and BRCApro) to identify an alternative strategy
      for genetic council targeted to the specified population. PATIENTS AND METHODS:
      The family history as well as individual information of two hundred unrelated
      probands who had completed BRCA1 and BRCA2 mutation screening was analyzed to
      assess the likelihood of a pathogenic mutation. A model was developed by
      empirical method. The performance of this model was validated in a separate
      patient cohort compared with BRCApro. RESULTS: Several factors were associated
      with mutations in univariate analysis and a logistic model was devised to
      estimate the probability for a proband of harboring a mutation in BRCA1 and/or
      BRCA2. Using a greater than 10% probability threshold, the highest accuracy was
      achieved by the established model when compared to other three models, presenting
      the highest sensitivity, PPV, NPV and area under ROC curve. The empirical model
      showed a better ROC curve compared to BRCApro in the verification cohort.
      CONCLUSION: A probability model targeted to Han Chinese population should be a
      useful tool in the genetic counseling for the specified ethnic. Its ability to
      predict BRCA2 mutation carriers needs to be improved.

PMID- 18343995
TI  - Evidences for association of the CASP8 -652 6N del promoter polymorphism with age
      at diagnosis in familial breast cancer cases.

PMID- 18343996
TI  - Guanidinoacetate decreases antioxidant defenses and total protein sulfhydryl
      content in striatum of rats.
AB  - Guanidinoacetate methyltransferase (GAMT) deficiency is an inherited
      neurometabolic disorder biochemically characterized by tissue accumulation of
      guanidinoacetate (GAA) and depletion of creatine. Affected patients present
      epilepsy and mental retardation whose pathogeny is unclear. In the present study
      we investigated the in vitro and in vivo (intrastriatal administration) effects
      of GAA on some oxidative stress parameters in rat striatum. Sixty-day-old rats
      were used for intrastriatal infusion of GAA. For the in vitro studies, 60-day-old
      Wistar rats were killed by decapitation and the striatum was pre-incubated for 1
      h at 37 degrees C in the presence of GAA at final concentrations ranging from 10
      to 100 microM. Parameters of oxidative stress such as total radical-trapping
      antioxidant potential (TRAP), antioxidant enzymes (SOD, GPx, and CAT), protein
      carbonyl and thiol contents were measured. DNA damage was also evaluated. Results
      showed that GAA administration (in vivo studies) or the addition of 100 microM
      GAA to assays (in vitro studies) significantly decreased TRAP, SOD activity, and
      total thiol levels in rat striatum. In contrast, this guanidino compound did not
      alter protein carbonyl content and the activities of CAT and GPx. DNA damage was
      not found after intrastriatal administration of GAA. The data indicate that the
      metabolite accumulating in GAMT deficiency decreases antioxidant capacity and
      total thiol content in the striatum. It is therefore presumed that this
      pathomechanism may contribute at least in part to the pathophysiology of the
      brain injury observed in patients affected by GAMT deficiency.

PMID- 18343997
TI  - Wireless endoscopy capsule remaining safely for a long time.

PMID- 18343998
TI  - Vaccine impedes the development of reflux-induced esophageal cancer in a surgical
      rat model: efficacy of the vaccine in a post-Barrett's esophagus setting.
AB  - PURPOSE: We developed and evaluated a GM-CSF whole-cell tumor vaccine for
      esophageal cancer. EXPERIMENTAL DESIGN: Cell lines derived from surgically
      induced rat reflux esophageal tumors were passaged in vitro and transfected with
      GM-CSF. First, the GM-CSF whole cell vaccine was evaluated against subcutaneously
      transplanted esophageal tumor cells. In a subsequent study, the vaccine was
      tested to see if it could reduce the incidence of cancer in the surgical reflux
      model. RESULTS: While subcutaneously transplanted tumor cells produced lasting
      tumors in PBS non-vaccinated placebo rats, transplanted tumors regressed and were
      immunologically rejected in animals vaccinated prior to implantation. In the
      surgical reflux model, the vaccine reduced the incidence of cancer from 17/23
      (74%) in the controls to 6/16 (38%) in the vaccinated animals (P = 0.046).
      CONCLUSIONS: The GM-CSF whole cell tumor vaccine effectively promoted a strong
      immune response against subcutaneously transplanted tumors and protected animals
      from developing esophageal cancer in the reflux model.

PMID- 18343999
TI  - JAK2V617F mutation in patients with portal vein thrombosis.
AB  - In a retrospective cohort, we investigated the presence of the JAK2V617F mutation
      in chronic non-cirrhotic portal vein thrombosis (PVT) patients, irrespective of
      the presence or absence of myeloproliferative diseases (MPDs). We identified 25
      patients in whom thrombophilia workup was completed. The diagnoses of MPDs were
      made according to the World Health Organization (WHO) criteria. JAK2V617F
      mutation analysis was performed by allele-specific polymerase chain reaction
      (PCR). There were 9 male and 16 female patients. Prior to JAK2V617F analysis,
      there were one or more thrombophilic risk factors in 19 patients (76%). The
      JAK2V617F mutation analysis revealed the presence of this mutation (all in the
      heterozygote state) in six patients (24%; two male, four female). Five of the six
      cases with prior clinical diagnosis of MPDs were found to have wild-type JAK2. We
      found that the addition of JAK2V617F analysis into the thrombophilia workup in
      patients with chronic PVT contributes to a 4% increase in the diagnosis of
      thrombophilic conditions.

PMID- 18344000
TI  - Is there an effect of print exposure on the word frequency effect and the
      neighborhood size effect?
AB  - Orthographic and phonological processing skills have been shown to vary as a
      function of reader skill (Stanovich & West, Reading Research Quarterly, 24, 402
      433, 1989; Unsworth & Pexman, Quarterly Journal of Experimental Psychology, 56A,
      63-81, 2003). One variable known to contribute to differences between readers of
      higher and lower skill is amount of print exposure: higher skilled readers read
      more often than lower skilled readers, and their increased print exposure is
      associated with faster responding to words and nonwords in lexical decision
      tasks. The present experiments examined the effect of print exposure on the word
      frequency effect and neighborhood size effect. We conclude that the different
      outcomes reported in previous studies (Chateau & Jared, Memory and Cognition, 28,
      143-153, 2000; Lewellen, Goldinger, Pisoni, & Greene, Journal of Experimental
      Psychology: General, 122, 316-330, 1993) were due to the type of nonwords used in
      the lexical decision task (regular nonwords versus pseudohomophones). Our results
      are explained in terms of differences in the reliance on orthographic and
      phonological information between readers of higher and lower print exposure.

PMID- 18344001
TI  - Predicting naming latencies with an analogical model.
AB  - Skousen's (1989, Analogical modeling of language, Kluwer Academic Publishers,
      Dordrecht) Analogical Model (AM) predicts behavior such as spelling pronunciation
      by comparing the characteristics of a test item (a given input word) to those of
      individual exemplars in a data set of previously encountered items. While AM and
      other exemplar-based models enjoy continuing success in their ability to predict
      what a participant's response to a given task will be, it does not yet include a
      widely tested mechanism for extending its predictions to other measures of
      interest in psycholinguistics such as response time (RT). This article reports
      the results of applying a formula derived in Estes (1959, in: Koch, Psychology: A
      study of a science, McGraw-Hill Book Co., Inc.) for approximating "mean predicted
      latency" in decision tasks to the alternative responses and their associated
      probabilities predicted by AM. The model is tested against six sets of data from
      previously published naming studies.

PMID- 18344002
TI  - Estimating the prevalence of injection drug users in the U.S. and in large U.S.
      metropolitan areas from 1992 to 2002.
AB  - This paper estimates the prevalence of current injection drug users (IDUs) in 96
      large U.S. metropolitan statistical areas (MSAs) annually from 1992 to 2002.
      Multiplier/allocation methods were used to estimate the prevalence of injectors
      because confidentiality restrictions precluded the use of other commonly used
      estimation methods, such as capture-recapture. We first estimated the number of
      IDUs in the U.S. each year from 1992 to 2002 and then apportioned these estimates
      to MSAs using multiplier methods. Four different types of data indicating drug
      injection were used to allocate national annual totals to MSAs, creating four
      distinct series of estimates of the number of injectors in each MSA. Each series
      was smoothed over time; and the mean value of the four component estimates was
      taken as the best estimate of IDUs for that MSA and year (with the range of
      component estimates indicating the degree of uncertainty in the estimates).
      Annual cross-sectional correlations of the MSA-level IDU estimates with measures
      of unemployment, hepatitis C mortality prevalence, and poisoning mortality
      prevalence were used to validate our estimates. MSA-level IDU estimates
      correlated moderately well with validators, demonstrating adequate convergence
      validity. Overall, the number of IDUs per 10,000 persons aged 15-64 years varied
      from 30 to 348 across MSAs (mean 126.9, standard deviation 65.3, median 106.6,
      interquartile range 78-162) in 1992 and from 37 to 336 across MSAs (mean 110.6,
      standard deviation 57.7, median 96.1, interquartile range 67-134) in 2002. A
      multilevel model showed that overall, across the 96 MSAs, the number of injectors
      declined each year until 2000, after which the IDU prevalence began to increase.
      Despite the variation in component estimates and methodological and component
      data set limitations, these local IDU prevalence estimates may be used to assess:
      (1) predictors of change in IDU prevalence; (2) differing IDU trends between
      localities; (3) the adequacy of service delivery to IDUs; and (4) infectious
      disease dynamics among IDUs across time.

PMID- 18344003
TI  - A theoretical study of cis-trans isomerisation in H-ZSM5: probing the impact of
      cluster size and zeolite framework on energetics and structure.
AB  - In this study the results from a series of calculations are reported that probe
      the influence of the QM cluster size and the extended framework treatment in
      ONIOM calculations. This is done by comparing the differences in the structures
      and energetics obtained during simulations of cis-trans isomerisation of butene
      in H-ZSM-5 at varying level of accuracy. Seven different models have been
      employed; 3T, 5T and 10T DFT cluster models, and to more effectively encode the
      extended framework of ZSM-5; 3T:46T, 5T:46T, 10T:46T DFT:MM ONIOM models, and a
      46T DFT cluster model. The results show that irrespective of the exact QM cluster
      size, relatively small gasphase clusters show clear limitations due to the
      neglect of the extended framework. In particular, the structural and electronic
      implications of using the different zeolite models have been rigorously assessed
      using the multivariate statistical method principal components analysis (PCA).

PMID- 18344004
TI  - Neural network-based QSAR and insecticide discovery: spinetoram.
AB  - Improvements in the efficacy and spectrum of the spinosyns, novel fermentation
      derived insecticide, has long been a goal within Dow AgroSciences. As large and
      complex fermentation products identifying specific modifications to the spinosyns
      likely to result in improved activity was a difficult process, since most
      modifications decreased the activity. A variety of approaches were investigated
      to identify new synthetic directions for the spinosyn chemistry including several
      explorations of the quantitative structure activity relationships (QSAR) of
      spinosyns, which initially were unsuccessful. However, application of artificial
      neural networks (ANN) to the spinosyn QSAR problem identified new directions for
      improved activity in the chemistry, which subsequent synthesis and testing
      confirmed. The ANN-based analogs coupled with other information on substitution
      effects resulting from spinosyn structure activity relationships lead to the
      discovery of spinetoram (XDE-175). Launched in late 2007, spinetoram provides
      both improved efficacy and an expanded spectrum while maintaining the exceptional
      environmental and toxicological profile already established for the spinosyn
      chemistry.

PMID- 18344005
TI  - Efficiency, thermodynamic and kinetic stability of marketed gadolinium chelates
      and their possible clinical consequences: a critical review.
AB  - Gadolinium-based contrast agents are widely used to enhance image contrast in
      magnetic resonance imaging (MRI) procedures. Over recent years, there has been a
      renewed interest in the physicochemical properties of gadolinium chelates used as
      contrast agents for MRI procedures, as it has been suggested that dechelation of
      these molecules could be involved in the mechanism of a recently described
      disease, namely nephrogenic systemic fibrosis (NSF). The aim of this paper is to
      discuss the structure-physicochemical properties relationships of marketed
      gadolinium chelates in regards to their biological consequences. Marketed
      gadolinium chelates can be classified according to key molecular design
      parameters: (a) nature of the chelating moiety: macrocyclic molecules in which
      Gd3+ is caged in the pre-organized cavity of the ligand, or linear open-chain
      molecules, (b) ionicity: the ionicity of the complex varies from neutral to tri
      anionic agents, and (c) the presence or absence of an aromatic lipophilic residue
      responsible for protein binding. All these molecular characteristics have a
      profound impact on the physicochemical characteristics of the pharmaceutical
      solution such as osmolality, viscosity but also on their efficiency in relaxing
      water protons (relaxivity) and their biodistribution. These key molecular
      parameters can also explain why gadolinium chelates differ in terms of their
      thermodynamic stability constants and kinetic stability, as demonstrated by
      numerous in vitro and in vivo studies, resulting in various formulations of
      pharmaceutical solutions of marketed contrast agents. The concept of kinetic and
      thermodynamic stability is critically discussed as it remains a somewhat
      controversial topic, especially in predicting the amount of free gadolinium which
      may result from dechelation of chelates in physiological or pathological
      situations. A high kinetic stability provided by the macrocyclic structure
      combined with a high thermodynamic stability (reinforced by ionicity for
      macrocyclic chelates) will minimize the amount of free gadolinium released in
      tissue parenchymas.

PMID- 18344006
TI  - Microbial degradation of 7-ketocholesterol.
AB  - 7-Ketocholesterol (7KC) is an oxidized derivative of cholesterol suspected to be
      involved in the pathogenesis of atherosclerosis and possibly Alzheimer's disease.
      While some oxysterols are important biological mediators, 7KC is generally
      cytotoxic and interferes with cellular homeostasis. Despite recent interest in
      preventing the accumulation of 7KC in a variety of matrices to avoid adverse
      biological effects, its microbial degradation has not been previously addressed
      in the peer-reviewed literature. Thus, the rate and extent of biodegradation of
      this oxysterol was investigated to bridge this gap. A wide variety of bacteria
      isolated from soil or activated sludge, including Proteobacterium Y-134,
      Sphingomonas sp. JEM-1, Nocardia nova, Rhodococcus sp. RHA1, and Pseduomonas
      aeruginosa, utilized 7KC as a sole carbon and energy source, resulting in its
      mineralization. Nocardia nova, which is known to produce biosurfactants, was the
      fastest degrader. This study supports the notion that microbial catabolic enzymes
      could be exploited to control 7KC levels in potential biotechnological
      applications for agricultural, environmental, or medical use.

PMID- 18344007
TI  - Unpasteurized milk consumption and subsequent risk of cancer.
AB  - Concerns have been raised regarding the possible adverse health effects of
      consumption of unpasteurized milk and risk of cancer. We examined the association
      of self-reported intake of unpasteurized milk with subsequent risk of cancer in a
      large population-based cohort study. The Iowa Women's Health Study is a
      prospective cohort study of 55-69 year old women at baseline in 1986. Of the
      41,836 women in the cohort at baseline, 22,808 cancer-free women completed the
      fourth follow-up questionnaire in 1997. Risk ratios (RR) and 95% confidence
      intervals (CI) were calculated using Cox proportional hazards regression
      analysis. Reported intake of unpasteurized milk was high: 59.2% consumed only as
      a child, 2.5% consumed only as an adult, and 16.5% consumed as a child and an
      adult. A total of 2,379 cancers were identified in the cohort at risk. Overall,
      the age-adjusted risk of cancer was lower among women who reported consumption of
      unpasteurized milk only as a child (RR = 0.90, 95% CI: 0.82-0.99) or as a child
      and an adult (RR = 0.85; 95% CI: 0.75-0.97). Adjustment for confounding factors
      attenuated these associations (RR = 0.92, 95% CI: 0.83-1.02 for consumption only
      as a child, and RR = 0.91; 95% CI: 0.79-1.04 for consumption as a child and an
      adult). These data suggest that consumption of unpasteurized milk does not
      increase risk of cancer.

PMID- 18344008
TI  - Evaluation of trace heavy metal levels of some fish species sold at retail in
      Kayseri, Turkey.
AB  - Cd, Ni, Cr, Zn, Cu and Pb concentrations of muscle tissue of 61 fish samples
      belonging to six fish species (Sparus auratus, Pomatomus saltatrix, Sarda sarda,
      Engraulis encrasicholus, Sander lucioperca, Scomber scombrus) retailed in
      Kayseri, Turkey were determined by flame atomic absorption spectrometry after wet
      digestion. Cd concentrations of at least 31 fish samples (50.8%) and Pb
      concentrations of at least six fish samples (9.8%) exceeded the corresponding
      Turkish permissible limit of 0.05 and 0.2 mg kg(-1) respectively whereas Zn
      concentrations of 11 fish samples (18%) exceeded the Turkish Food Codex limits of
      50 mg kg(-1) for Zn. Cu concentrations of all fish species analyzed (100%) were
      below the corresponding Turkish legislations of 20 mg kg(-1). No limits were
      established concerning Ni and Cr concentrations in fish by the Turkish
      governmental authorities.

PMID- 18344009
TI  - Phosphate adsorption characteristics at the sediment-water interface and
      phosphorus fractions in Nansi Lake, China, and its main inflow rivers.
AB  - Phosphorus fractions and phosphate adsorption characteristics of 16 sediments
      from a shallow freshwater lake (Nansi Lake, China) and its inflow estuaries were
      investigated. In the present study, the sediment phosphorus is fractionated into
      exchangeable P (exch-P), Al-P, Fe-P, Ca-P, organic P (OP), inorganic P (IP) and
      total P (TP). The results show that the total phosphorus (TP) content in the
      sediments ranges from 571.67 to 1,113.55 mg kg(-1), and calcium bound phosphorus
      (Ca-P) is the main fraction of IP. The biologically available phosphorus (BAP)
      ranges from 32.02 to 229.67 mg kg(-1) in the Nansi Lake sediments. Phosphate
      adsorption on the sediments mainly occurs within 10 h and is completed within 48
      h. The content of native adsorbed phosphorus (omega(NAP)) varies greatly from
      6.05 to 194.37 mg kg(-1), showing a significant correlation with the total
      maximal amount of phosphorus adsorbed (TQ(max)). Adsorption efficiency (m) ranges
      from 574.79 to 3,220.68 l kg(-1) and zero equilibrium phosphorus concentration
      (C(EPC)) ranges from 0.010 to 0.157 mg l(-1). After the South-to-North Water
      Diversion Project, the inherent phosphorus present in sediments will be a major
      threat to the diverted water quality and be a predominant factor determining the
      trophic status of the lake even if the external load is reduced.

PMID- 18344010
TI  - Glycerol stimulates innate chaperoning, proteasomal and stress-resistance
      functions: implications for geronto-manipulation.
AB  - Aging is associated with accumulation of toxic intracellular and extracellular
      protein aggregates. Cells manage "aged" proteins by mobilizing their molecular
      chaperones or heat shock proteins that are also considered as determinants of
      lifespan in diverse species. In this study, we tested whether an exogenous
      addition of the non-toxic chemical chaperone 'glycerol' could elicit stress and
      geronto-protective activities. We found that glycerol enhanced chaperoning of
      heat-denatured proteins. In addition to stimulating proteasome activity, glycerol
      led to an increased expression of the stress chaperone 'mortalin' and decreased
      p53 function in human cells. Glycerol-fed worms exhibited thermo-tolerance and
      lower level of age-associated auto-fluorescence. Through the combined stimulation
      of the proteasome and chaperoning activities of mortalin, in particular, glycerol
      treatment resulted in increased survival and fitness against oxidative- and heat
      stress. These results may have significant implications in the use of glycerol as
      a candidate geronto-modulator in development of practical interventions for
      "healthy aging".

PMID- 18344011
TI  - Adsorption and polymerization of amino acids on mineral surfaces: a review.
AB  - The present paper offers a review of recent (post-1980) work on amino acid
      adsorption and thermal reactivity on oxide and sulfide minerals. This review is
      performed in the general frame of evaluating Bernal's hypothesis of prebiotic
      polymerization in the adsorbed state, but written from a surface scientist's
      point of view. After a general discussion of the thermodynamics of the problem
      and exactly what effects surfaces should have to make adsorbed-state
      polymerization a viable scenario, we examine some practical difficulties in
      experimental design and their bearing on the conclusions that can be drawn from
      extant works, including the relevance of the various available characterization
      techniques. We then present the state of the art concerning the mechanisms of the
      interactions of amino acids with mineral surfaces, including results from
      prebiotic chemistry-oriented studies, but also from several different fields of
      application, and discuss the likely consequences for adsorption selectivities.
      Finally, we briefly summarize the data concerning thermally activated amide bond
      formation of adsorbed amino acids without activating agents. The reality of the
      phenomenon is established beyond any doubt, but our understanding of its
      mechanism and therefore of its prebiotic potential is very fragmentary. The
      review concludes with a discussion of future work needed to fill the most
      conspicuous gaps in our knowledge of amino acids/mineral surfaces systems and
      their reactivity.

PMID- 18344013
TI  - Genetic variants of transferrin in cystic fibrosis.
AB  - BACKGROUND: Genetic polymorphism of serum transferrin (Tf) was studied in order
      to differentiate between protein genetic variants and congenital disorders of
      glycosylation (CDG), further focusing on unusual findings. METHODS: Screening of
      Tf hypoglycosylation was carried out by isoelectric focusing with direct
      immunofixation and Coomassie blue staining in 100 healthy controls and a group of
      1247 patients with various symptoms and diagnoses. RESULTS: Of the seven
      different genotypes detected, a significantly higher (p = 0.004) frequency of Tf
      C1C2 was found among 92 patients with cystic fibrosis; only the most severe DF508
      mutation (in either homozygous or heterozygous form) was regularly present in the
      carriers of this Tf genotype, in contrast to those with the Tf C1C1 variant.
      CONCLUSIONS: Association of Tf C2 allele with various malfunctions has been
      noticed before, but is so far unresolved. This is the a report on increased
      frequency of Tf C1C2 genotype found in cystic fibrosis. Analysis of larger
      samples and independent confirmation of our results are needed.

PMID- 18344012
TI  - Leukoencephalopathies associated with inborn errors of metabolism in adults.
AB  - The discovery of a leukoencephalopathy is a frequent situation in neurological
      practice and the diagnostic approach is often difficult given the numerous
      possible aetiologies, which include multiple acquired causes and genetic diseases
      including inborn errors of metabolism (IEMs). It is now clear that IEMs can have
      their clinical onset from early infancy until late adulthood. These diseases are
      particularly important to recognize because specific treatments often exist. In
      this review, illustrated by personal observations, we give an overview of late
      onset leukoencephalopathies caused by IEMs.

PMID- 18344014
TI  - Effect of repeated application of fenthion as a mosquito larvicide on Nile
      tilapia (Oreochromis niloticus) inhabiting selected water canals in Sri Lanka.
AB  - Health status of feral Nile tilapia following repeated applications of fenthion
      as a mosquito larvicide to selected water canals in Sri Lanka was assessed. With
      three spray applications of fenthion to the study sites at weekly intervals at
      the concentration recommended for mosquito control, condition factor and brain
      acetylcholinesterase activity of the fish were depressed in a time dependent
      manner. Prominent histopathological alterations displayed were gill hyperplasia
      and telangiectasis and vacoulation of hepatocytes. Observed ill health effects of
      fenthion on the fish demonstrate probable ecological risk to the fish populations
      inhabiting the water canals which receive repeated inputs of fenthion.

PMID- 18344015
TI  - Polybrominated diphenyl ethers in leaves and soil from typical electronic waste
      polluted area in South China.
AB  - Polybrominated diphenyl ethers (PBDEs) in leaves and soil from typical e-waste
      polluted area in South China were investigated. The concentrations (ng/g dry
      weight) of PBDE congeners and summation operatorPBDE of five leaf samples were
      much lower than those in soil sample. The general patterns of summation di-BDEs
      to summation hepta-BDEs percentage distribution in leaf samples were similar to
      those of the soil sample, except the percentage of BDE209 which were lower than
      in soil. The percentages of summation di-BDEs to summation hepta-BDEs in soil
      were in the range of those in leaf samples. The results showed that the
      contamination of PBDEs in the leaf samples had good correlation with the soil
      around them.

PMID- 18344016
TI  - Binding of nontarget microorganisms from food washes to anti-Salmonella and anti
      E. coli O157 immunomagnetic beads: minimizing the errors of random sampling in
      extreme dilute systems.
AB  - For most applications, 3-5 observations, or samplings (n), are utilized to
      estimate total aerobic plate count in an average population (MU) that is greater
      than about 50 cells, or colony forming units (CFU), per sampled volume. We have
      chosen to utilize a 6 * 6 drop plate method for bacterial colony selection
      because it offers the means to rapidly perform all requisite dilutions in a 96
      well format and plate these dilutions on solid media using minimal materials.
      Besides traditional quantitative purposes, we also need to select colonies which
      are well-separated from each other for the purpose of bacterial identification.
      To achieve this goal using the drop plate format requires the utilization of very
      dilute solutions (MU < 10 CFUs per sampled drop). At such low CFU densities the
      sampling error becomes problematic. To address this issue we produced both
      observed and computer-generated colony count data and divided a large sample of
      individual counts randomly into N subsamples each with n = 2-24 observations (N *
      n = 360). From these data we calculated the average total mean-normalized (x
      (tot), n = 360) deviation of the total standard deviation (s (tot)) from each jth
      subsample's estimate (s ( j )), which we call Delta. When either observed or
      computer-generated Delta values were analyzed as a function of x-(tot), a set of
      relationships (infinity -2? -x(tot)) were generated which appeared to converge at
      an n of about 18 observations. This finding was verified analytically at even
      lower CFU concentrations (-x(tot) ~ 1 - 10 CFUs per observation). Additional
      experiments using the drop plate format and n = 18 samplings were performed on
      food samples along with most probable number (MPN) analyses and it was found that
      the two enumeration methods did not differ significantly.

PMID- 18344017
TI  - Off-target activity of TNF-alpha inhibitors characterized by protein biochips.
AB  - Tumor necrosis factor-alpha inhibitors are widely and successfully used to treat
      rheumatic diseases. However, significant side effects have been reported. To
      detect the potential off-target activities of such inhibitors we characterized
      two therapeutic antibodies (adalimumab, infliximab) and one receptor fusion
      protein (etanercept) on protein biochips (UNIchip AV-400) containing a printed
      serial dilution of tumor necrosis factor-alpha and about 384 different human
      proteins. Etanercept binds to ten proteins (affinity: 20-33% of tumor necrosis
      factor-alpha recognition), and six of these proteins are related to ribosomal
      proteins. Interestingly, adalimumab binds to the same six proteins related to
      ribosomal proteins (affinity: 12-18%) as well as to four proteins crucially
      involved in ribosomal protein synthesis. Alignment of protein sequences indicates
      no significant sequence homology between these ten proteins bound by the
      biological drugs with the highest off-target activities. Taken together, our in
      vitro results demonstrate that a significant number of proteins are recognized by
      tumor necrosis factor-alpha inhibitors and are related to ribosome biogenesis.

PMID- 18344018
TI  - Kallikrein-related peptidases.
AB  - Kallikrein 1 (KLK1), a key component of the kallikrein-kinin system, originates
      from a locus on the long arm of chromosome 19 that contains several related
      serine endopeptidases. The biological role of these kallikrein-related peptidases
      is not clear, but emerging evidence suggests that they might be important in
      several physiological systems, e.g., in male reproduction, skin homeostasis,
      tooth enamel formation and neural development and plasticity. The kallikrein
      locus has undergone some major evolutionary events. Most spectacular are
      relatively recent duplications of KLK1 that have created 13 and 9 functional
      genes that are unique to the mouse and the rat, respectively. Human paralogs are
      KLK2 and KLK3: the latter encoding the cancer biomarker prostate-specific
      antigen. In this review on kallikrein-related peptidases, the focus is on their
      evolution, their role in skin homeostasis and semen liquefaction, and their
      utility as cancer biomarkers.

PMID- 18344019
TI  - Melatonin, hormone of darkness and more: occurrence, control mechanisms, actions
      and bioactive metabolites.
AB  - In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking
      and systemically acting chronobiotic. These effects are largely explained by
      actions via G protein-coupled membrane receptors found in the suprachiasmatic
      nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic
      (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites
      and radical-scavenging properties contribute to the actions of melatonin.
      Regulation of pineal melatonin biosynthesis is largely explained by control
      mechanisms acting on arylalkylamine N-acetyltransferase, at the levels of gene
      expression and/or enzyme stability influenced by phosphorylation and interaction
      with 14-3-3 proteins. Melatonin is not only a hormone but is also synthesized in
      numerous extrapineal sites, in which it sometimes attains much higher quantities
      than in the pineal and the circulation. It is also present in many taxonomically
      distant groups of organisms, including bacteria, fungi, and plants. Moreover,
      melatonin is a source of bioactive metabolites, such as 5-methoxytryptamine, N(1)
      acetyl-N(2)-formyl-5-methoxykynuramine and N(1)-acetyl-5-methoxykynuramine.

PMID- 18344020
TI  - The utility F-box for protein destruction.
AB  - A signature feature of all living organisms is their utilization of proteins to
      construct molecular machineries that undertake the complex network of cellular
      activities. The abundance of a protein element is temporally and spatially
      regulated in two opposing aspects: de novo synthesis to manufacture the required
      amount of the protein, and destruction of the protein when it is in excess or no
      longer needed. One major route of protein destruction is coordinated by a set of
      conserved molecules, the F-box proteins, which promote ubiquitination in the
      ubiquitin-proteasome pathway. Here we discuss the functions of F-box proteins in
      several cellular scenarios including cell cycle progression, synapse formation,
      plant hormone responses, and the circadian clock. We particularly emphasize the
      mechanisms whereby F-box proteins recruit specific substrates and regulate their
      abundance in the context of SCF E3 ligases. For some exceptions, we also review
      how F-box proteins function through non-SCF mechanisms.

PMID- 18344021
TI  - ADAM proteases: ligand processing and modulation of the Notch pathway.
AB  - ADAM metalloproteases play important roles in development and disease. One of the
      key functions of ADAMs is the proteolytic processing of Notch receptors and their
      ligands. ADAM-mediated cleavage of Notch represents the first step in regulated
      intramembrane proteolysis of the receptor, leading to activation of the Notch
      pathway. Recent reports indicate that the transmembrane Notch ligands also
      undergo ADAM-mediated processing in cultured cells and in vivo. The proteolytic
      processing of Notch ligands modulates the strength and duration of Notch signals,
      leads to generation of soluble intracellular domains of the ligands, and may
      support a bi-directional signaling between cells.

PMID- 18344022
TI  - Myosin I: from yeast to human.
AB  - Myosin I is a non-filamentous, single-headed, actin-binding motor protein and is
      present in a wide range of species from yeast to man. The role of these class I
      myosins have been studied extensively in simple eukaryotes, showing their role in
      diverse processes such as actin cytoskeleton organization, cell motility, and
      endocytosis. Recently, studies in metazoans have begun to reveal more specialized
      functions of myosin I. It will be a major challenge in the future to examine the
      physiological functions of each class I myosin in different cell types of
      metazoans.

PMID- 18344023
TI  - Inhibition of plasminogen activator inhibitor-1 expression in vascular smooth
      muscle cells by protoporphyrins through a heme oxygenase-independent mechanism.
AB  - Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has been
      shown to play a regulatory role in the expression of plasminogen activator
      inhibitor-1 (PAI-1), a risk factor for vascular disease. Accordingly, we examined
      the effect of protoporphyrins, both HO inhibitors and activators, on PAI-1
      expression in human vascular smooth muscle cells (VSMCs). Tin-protoporphyrin
      (SnPP) markedly inhibited the transforming growth factor beta1 (TGFbeta1)-induced
      expression of PAI-1 protein. Protoporphyrins, whether they are inhibitors or
      activators of HO, produced a similar inhibitory effect. However, SnPP had no
      effect on the level of PAI-1 mRNA transcripts. Knockdown of human HO-1 with a
      specific siRNA did not reduce the PAI-1 protein level in TGFbeta1-treated cells.
      In addition, the proteasome inhibitor lactacystin reversed the inhibitory effect
      of SnPP on PAI-1 protein expression. Both cobalt-protoporphyrin (CoPP) and CoCl2
      markedly induced HO-1 expression. However, CoPP did not affect PAI-1 gene
      expression, whereas CoCl2 upregulated PAI-1 mRNA in a dose-dependent manner. Our
      results demonstrate that protoporphyrins can block the TGFbeta1-mediated
      induction of PAI-1 protein in VSMCs and that this inhibitory effect is
      independent of HO activity.

PMID- 18344024
TI  - Delivery of adjuvant sequential dose-dense FEC-Doc to patients with breast cancer
      is feasible, but dose reductions and toxicity are dependent on treatment
      sequence.
AB  - INTRODUCTION: This study prospectively investigates the impact of dose
      densification and altering sequence of fluorouracil, epirubicin and
      cyclophosphamide [FEC(100)] and docetaxel [Doc] on dose delivery and tolerability
      of adjuvant chemotherapy in breast cancer patients. METHODS: 117 patients with
      high-risk primary operable breast cancer were randomized (1:1:2:2) to
      conventional (three cycles of 3-weekly FEC(100) then three cycles of 3-weekly Doc
      100 mg/m(2) or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day
      cycles of FEC(75) then four 2-weekly cycles of Doc 75 mg/m(2), or the reverse).
      In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as
      secondary prophylaxis in conventional arms. RESULTS: The primary endpoint was the
      proportion of patients completing intended cycles at relative dose intensity
      >or=85% and this was achieved by 95% of patients in each group except for the
      ddDoc-->FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC
      and 11% for docetaxel, compared with the conventional arms (both P < 0.001). Doc
      dose reductions were more frequent with dd treatment and when Doc was given after
      FEC. Grade 3-4 neutropenia was significantly more frequent with conventional
      treatment, while fatigue and hand-foot syndrome were numerically more common with
      dd treatment, particularly when Doc was given after FEC. Discussion Delivery of
      adjuvant sequential ddFEC and Doc is feasible with growth factor support, and
      chemotherapy sequence appeared to affect delivery of target doses and toxicity.

PMID- 18344025
TI  - VEGF165 expression in the tumor microenvironment influences the differentiation
      of bone marrow-derived pericytes that contribute to the Ewing's sarcoma
      vasculature.
AB  - We previously demonstrated that bone marrow (BM) cells migrate to Ewing's tumors
      and differentiate into endothelial cells within the tumor vasculature. Recent
      evidence suggests that the roles of BM cells in tumors are more diverse. We
      investigated whether non-endothelial cell types critical for tumor vessel
      development are also derived from migrated BM cells. We utilized BM
      transplantation with GFP(+) transgenic mice as BM donors and nude mice as
      recipients to track the fate of migrated BM cells. After engraftment, we injected
      recipient mice either subcutaneously or intramuscularly with Ewing's sarcoma
      cells. We labeled functional tumor vessels using intravascular perfusion staining
      with tomato lectin. We assessed BM cell recruitment/differentiation within the
      tumor microenvironment using immunohistochemistry. Ewing's tumors contained BM
      derived cells that had differentiated into endothelial cells lining perfused
      tumor vessels. A substantial fraction of recruited BM cells also resided in the
      vessel vicinity and expressed desmin and PDGFR-beta, indicating smooth muscle
      cell differentiation. In order to further characterize the role of
      stem/progenitor cells in Ewing's sarcoma, we sorted Tie2(-) BM cells from Tie2
      GFP transgenic mice and then injected them intravenously into Ewing's tumor
      bearing mice. Tie2(-) BM progenitors migrated to Ewing's tumors and
      differentiated into Tie2(+) cells occupying a perivascular residence and
      expressing alpha-smooth muscle actin, desmin and PDGFR-beta, as well as VEGFR-2.
      We did not observe differentiation of Tie2(-) cells into Tie2(+) perivascular
      cells in VEGF(165)-inhibited TC/siVEGF(7-1) tumors. The differentiation of Tie2(
      ) BM cells into Tie2(+) cells in parental but not VEGF(165)-inhibited tumors
      indicates that the tumor microenvironment may influence the differentiation
      pathway.

PMID- 18344026
TI  - [Treatment of acute myocardial infarction].

PMID- 18344027
TI  - Pathophysiology of myocardial infarction: protection by ischemic pre- and
      postconditioning.
AB  - One or several short cycles of ischemia/reperfusion before (preconditioning) or
      after (postconditioning) a sustained coronary occlusion with subsequent
      reperfusion reduce the ultimate infarct size. The protection is potent, but
      limited to a narrow time frame. In animal experiments, a complex signal
      transduction cascade was identified which results specifically in a reduction of
      reperfusion injury. There is evidence for both ischemic pre- and postconditioning
      in patients with coronary artery disease.

PMID- 18344028
TI  - [Optimizing systems of care for patients with acute myocardial infarction. STEMI
      networks, telemetry ECG, and standardized quality improvement with systematic
      data feedback].
AB  - Rapid revascularization of the infarct-related artery importantly affects
      prognosis in the treatment of acute ST elevation myocardial infarction (STEMI).
      Treatment results can be improved significantly when a STEMI-specific structure
      of care is created and when systematic quality improvement measures are
      implemented. The necessary structural measures include establishing or
      participating in myocardial infarction networks. When local hospitals collaborate
      in a network, it becomes feasible to offer round-the-clock primary coronary
      intervention to patients of those participating hospitals that do not have a
      catheterization laboratory on site. Another important structural step is to
      acquire and install prehospital twelve-lead ECG systems capable of remote
      telemetric transmission. This provides a solid basis for diagnosing STEMI with
      speed and accuracy and can prove to be highly effective in anchoring the chain of
      alert and treatment. As a consequence, two important goals can be realized: (1)
      intentionally bypassing the non-interventional hospital, and (2) systematically
      bypassing the emergency room of the interventional center. Both of these measures
      entail important time savings. An efficient instrument for improving treatment
      times is the implementation of a standardized quality improvement process with
      formalized data collection and analysis as well as with systematic data feedback
      to all systems and individuals involved in the early phase of treating STEMI
      patients within the hospital network including the emergency medical responder
      systems. The positive effect of such data feedback on treatment quality is
      contingent on the perception by all those involved that the data obtained for
      each patient are absolutely valid. Thus, those data need to be verifiable and an
      independent monitoring process should be created.Furthermore, the systematic use
      of standardized risk scores should be promoted in an effort to compare and adjust
      patient risk when analyzing network data. It is critically important that all
      appropriate patients-including those with a high risk of mortality--have access
      to rapid interventional treatment. Only when the individual risk of treated
      patients is taken into account will it be possible to compare quality of care and
      mortality rates. In general, the comparison between different hospitals, systems
      and regions is highly problematic and not feasible without considering local
      factors. It harbors the danger of inducing changes in practice in order to
      compete rather than in order to advance patient care, and thus it may be
      counterproductive when such a comparison leads to the implication that treatment
      may have been inferior. Therefore, the comparison of results (e.g., treatment
      times and mortality rates) should be undertaken as much as possible within an
      established system, with the use of a "before and after" design. Quality, then,
      will be defined as a documented consistent effort to improve results, and this
      approach will be distinctly productive. It is of fundamental importance that the
      involved hospitals, physicians and emergency staff perceive themselves as a team.
      The structures and processes outlined above can and should be applied broadly.
      The necessary resources will need to be provided through political and societal
      consensus. The multicenter FITT-STEMI project ("Feedback Intervention and
      Treatment Times in ST-Elevation Myocardial Infarction") is currently pursuing
      such an approach.

PMID- 18344029
TI  - [Primary Coronary Intervention (PCI) within the myocardial infarction network
      system in a German city (Essen)].
AB  - In a German city (Essen, 490,000 people), a new network system for patients with
      ST elevation myocardial infarction (STEMI) was established in 2004. This included
      a so-called integrated care model (IV model) by participation of insurance
      companies. In a cooperative structure between invasive and noninvasive hospitals,
      general practitioners and cardiologists as well as emergency systems it could be
      realized, that every patient with STEMI will be treated by primary percutaneous
      coronary intervention (PCI) as soon as possible according to the current
      guidelines. The patient characteristics (age, gender, comorbidity, medication)
      were comparable to other trials and registries. The primary success rate was high
      (96.4%). The acute in-hospital results demonstrated a low mortality (7.6%). The
      time periods of delay were comparable to other registries. The symptom-to-balloon
      time was 239 min, the medical contact-to-balloon time 95 min, the door-to-balloon
      time 60 min, and the puncture-to-balloon time 18 min (median values). The STEMI
      network system in Essen demonstrates the possibility of modern therapy in
      patients with myocardial infarction (primary PCI) in a cooperative modality
      between all participants in the health-care system.

PMID- 18344030
TI  - [Redefinition of myocardial infarction--relevance of biomarkers].
AB  - Myocardial infarction (MI) as an acute and life-threatening complication of
      coronary heart disease is one of the most frequent causes of death in Germany.
      Therefore, diagnosis, risk stratification and treatment of acute MI are of great
      clinical relevance. Specific recommendations concerning diagnosis of acute MI can
      be found in current guidelines of the European Society of Cardiology (ESC) and
      the German Cardiac Society, as well as in a consensus document "Universal
      definition of myocardial infarction", which has been published at the end of
      2007. Here, cardiac markers, namely cardiac troponins, play a central role as a
      criterion for the diagnosis of myocardial infarction. Moreover, cardiac troponins
      provide prognostic information and are of great value for risk stratification of
      patients. Measurement of creatine kinase CK-MB is an alternative to troponin
      measurement, but is only recommended, if troponins are not available. As a cutoff
      value for cardiac biomarkers the 99th percentile of a healthy reference
      population has been defined. However, assays that are used for routine testing
      require adequate precision. Besides established biomarkers, several novel markers
      have been evaluated in clinical studies in recent years. Especially B-type
      natriuretic peptides (BNP and NT-proBNP) and C-reactive protein (CRP) have gained
      great interest and sufficient data has been gathered, justifying clinical
      application of these novel markers. As a consequence, BNP/NT-proBNP and CRP are
      mentioned in the current guidelines of the ESC as appropriate biomarkers for risk
      stratification. The clinical relevance of other novel biomarkers remains
      uncertain and necessitates further studies.

PMID- 18344031
TI  - [Role of deformation imaging in diagnosing myocardial ischemia].
AB  - Velocity and deformation imaging by Doppler and newer techniques based on
      "speckle tracking" in 2-D datasets have substantially added to the ability of
      echocardiography to detect myocardial ischemia. Typical parameters include tissue
      velocities and regional deformation ("strain") and deformation rate ("strain
      rate"), which with the Doppler-independent new techniques ("2-D strain",
      "velocity vector imaging") can be measured in several directions, largely
      independent of insonation angle. All of these techniques can be readily combined
      with stress echocardiography; so far, published results are mostly based on the
      combination with dobutamine echocardiography. Typical signs of myocardial
      ischemia include a decrease in tissue velocities, deformation rates, and
      deformation. Additionally, systolic deformation occurs later in systole and often
      still goes on after aortic valve closure (postsystolic deformation). While tissue
      velocities are unable to clearly identify regional ischemia because of tethering
      of the neighboring wall segments and a physiological variation in regional tissue
      velocities, deformation parameters are better suited to detect regional ischemia.
      The limited literature on the detection of myocardial ischemia by these
      techniques clearly shows a value of velocity and deformation imaging especially
      in those cases where qualitative visual assessment of wall motion remains
      ambiguous. Due to rapid evolution of these techniques, a final assessment of
      their potential is not possible yet.

PMID- 18344032
TI  - [Cardiac magnetic resonance imaging in the diagnosis of acute coronary syndrome.
      Basics and clinical value].
AB  - In contrast to chronic myocardial infarction, data concerning the value of
      cardiac magnetic resonance imaging in patients with acute onset of chest pain are
      still rare. Even in the presence of characteristic clinical parameters, cardiac
      magnetic resonance imaging might provide independent evidence especially in the
      absence of typical ECG alterations and prior to biomarker elevation. Besides the
      ability to demonstrate wall motion abnormalities cardiac magnetic resonance
      imaging gains additional potential as to the detection of myocardial edema,
      microvascular obstruction (no-reflow) and myocardial necrosis. However, cardiac
      magnetic resonance imaging is expensive and time-consuming, and therefore may not
      be cost-effective. At present, a lack of sufficient diagnostic and prognostic
      data would make cardiac magnetic resonance imaging unsuitable for routine
      stratification of chest pain patients in an emergency department.

PMID- 18344033
TI  - Prognostic impact of contrast-enhanced CMR early after acute ST segment elevation
      myocardial infarction (STEMI) in a regional STEMI network: results of the
      "Herzinfarktverbund Essen".
AB  - BACKGROUND AND PURPOSE: In acute ST segment elevation myocardial infarction
      (STEMI), rapid restoration of epicardial coronary blood flow and myocardial
      perfusion limits infarct size and improves survival. Primary percutaneous
      coronary intervention (PCI) is superior to systemic fibrinolysis when instantly
      performed by experienced operators. The "Herzinfarktverbund Essen" (HIVE) is an
      urban STEMI network supporting direct patient transfer for primary PCI to four
      PCI centers covering a city area of 600,000 inhabitants. Integrated health care
      is an optional part of the HIVE allowing for reimbursement of medical innovations
      such as the evaluation of infarct size and the presence and extent of
      microvascular obstruction by contrast-enhanced cardiac magnetic resonance (CMR).
      The aim of this study was to assess the prognostic impact of contrast-enhanced
      CMR in the patient cohort of a regional STEMI network. PATIENTS AND METHODS:
      Within the 1st year (09/2004 to 08/2005) of the HIVE registry, 489 patients with
      acute myocardial infarction were treated in the four primary PCI centers. In one
      of the centers, including 143 patients, early CMR imaging using a standardized MR
      protocol for infarct quantification was performed whenever possible. Patients
      with hemodynamic instability, emergency coronary artery bypass grafting,
      resuscitation or death prior to CMR, claustrophobia, and other general
      contraindications to MRI had to be excluded, leaving 67 patients (54 male; mean
      age 61 +/- 12 years) for final evaluation. CMR was performed 4.5 +/- 2.5 days
      after admission on a 1.5-T MR scanner (Sonata, Siemens Medical Solutions,
      Erlangen, Germany) including steady-state free precession (SSFP) cine imaging for
      left ventricular function and single-shot inversion-recovery SSFP imaging for
      delayed enhancement (DE) and no-reflow (NR) evaluation following injection of 0.2
      mmol/kg body weight gadodiamide (Omniscan, GE Healthcare Buchler, Munich,
      Germany). NR and DE volumes were calculated from single-shot short-axis stacks
      taken within the 1st minute following gadodiamide infusion by manual planimetry
      and summation of disks. 1-year follow-up data (telephone interview) for major
      adverse cardiac events (MACE: cardiac death, myocardial infarction, and
      rehospitalization for congestive heart failure, angina pectoris, or
      revascularization) were available for all patients. RESULTS: DE as a measure of
      infarct size was 9% +/- 7% (range 0-33%) of left ventricular mass (LVM), and mean
      volume of microvascular obstruction was 2% +/- 3% (range 0-17%). Microvascular
      obstruction was present in 61% of patients. 16 MACE (one cardiac death, one
      myocardial infarction, and 14 rehospitalizations for congestive heart failure or
      unstable angina pectoris with PCI in six cases) occurred within the follow-up
      period of 430 +/- 63 days. Patients with MACE had larger infarcts (14% +/- 10%
      vs. 8% +/- 6% DE), lower left ventricular ejection fraction (LVEF 44% +/- 17% vs.
      48% +/- 14%) and larger NR (3% +/- 5% vs. 2% +/- 3%). Using a stepwise logistic
      regression model, only NR > 0.5% of LVM was independently related to outcome
      (odds ratio = 3.9, confidence interval 1.1-13.9). CONCLUSION: NR as a correlate
      of microvascular obstruction remains independently related to prognosis in
      patients with acute myocardial infarction treated by PCI.

PMID- 18344034
TI  - [Facilitated PCI: did the concept fail?].
AB  - BACKGROUND: Direct percutaneous coronary intervention (PCI) can be considered the
      gold standard of reperfusion therapy. For patients with need for transfer, the
      question of antithrombotic pretreatment arises. CONCEPT OF FACILITATED PCI: With
      the concept of facilitated PCI the advantages of fibrinolysis, namely the rapid
      and ubiquitous availability, should be combined with the advantages of immediate
      PCI. With a pretreatment using fibrinolytics, glycoprotein IIb/IIIa inhibitors
      (GPI) or the combination of both (in that case a fibrinolytic in half dosage
      only), it was aimed to achieve reperfusion before a planned PCI. Facilitated PCI
      was expected to improve the rate of open vessels prior to PCI, thereby reducing
      infarct size, improving clinical outcome, and the success rate of PCI. CLINICAL
      TRIALS: The concept of facilitated PCI was evaluated in two major randomized
      trials (ASSENT-4 PCI, FINESSE) as well as in one meta-analysis. Despite an
      increase of 20% of patients with patent infarct-related arteries (TIMI 3) before
      PCI, the clinical outcome, especially mortality, reinfarction rate and heart
      failure rate, did not improve. Moreover, the bleeding rate increased and even a
      higher rate of cerebral bleeds was seen, predominantly with full-dose
      fibrinolysis. POSSIBLE REASONS FOR THE LACK OF SUCCESS WITH FACILITATED PCI:
      Patency (TIMI 3) of the coronary arteries was 20% higher in the facilitated PCI
      arms of the trials. However, all patients were at risk of bleeding complications.
      Also the inclusion of patients with myocardial infarction in a later phase and
      the inclusion of patients at lower risk may have contributed to the somewhat
      disappointing results of facilitated PCI. GUIDELINES: Recent American College of
      Cardiology/American Heart Association (ACC/AHA) guidelines recommend facilitated
      PCI (class IIb), if all of the following criteria are met: (1) patients at high
      risk, (2) PCI not available within 90 min, (3) low risk of bleed. A planned
      reperfusion strategy using full-dose fibrinolysis followed by immediate PCI may
      be harmful (class III). In addition, a further restriction to patients in the
      early phase of myocardial infarction (< 3 h) should be considered. In the small
      subset of carefully selected patients, a combination of GPI and half-dose
      fibrinolytic could be appropriate.

PMID- 18344035
TI  - [STEMI network Essen-in-hospital results].
AB  - BACKGROUND AND PURPOSE: The myocardial infarction network "Herzinfarktverbund
      Essen", existing since 2004, was designed to introduce guideline therapy of ST
      elevation myocardial infarction (STEMI) into everyday clinical practice using
      primary percutaneous coronary intervention (PCI) as the preferred reperfusion
      strategy, early prescribing recommended medication and optimizing patient's
      pathway from the first symptom to rehabilitation in a city of 580,000
      inhabitants. PATIENTS AND METHODS: In the 1st year, 489 patients were treated in
      five high-volume PCI centers. 444 primary PCIs were performed (90.8%). RESULTS:
      In-hospital mortality was 7.6% and thus lower than in other, historical STEMI
      registers with similar baseline characteristics but lower PCI rate. The best risk
      predictor was left ventricular function. Patients with an ejection fraction (EF)
      <or= 30% had a 27 times higher mortality risk than those with normal EF.
      Guideline-recommended medication was prescribed in 75% of patients
      (acetylsalicylic acid [ASS], clopidogrel, beta-blockers, and statins) and in 71%,
      respectively, with additional ACE inhibitor (five drugs). 72% of these patients
      were referred to rehabilitation therapy. CONCLUSION: The "Herzinfarktverbund
      Essen" demonstrates, that implementing guideline-conformal therapy into an urban
      area may result in a lower in-hospital mortality, a higher rate of patients
      prescribed recommended medication and a stronger patient adherence to ambulant
      therapy.

PMID- 18344036
TI  - [STEMI network Essen--results after 1 year].
AB  - The myocardial infarction network "Herzinfarktverbund Essen" was initiated on
      September 1, 2004 in order to establish a standardized strategy and therapy for
      patients with ST elevation myocardial infarction (STEMI) in the city of Essen.
      The primary goal is the immediate reopening of the infarcted vessel by direct
      transfer of the patient to a hospital with 24-h stand-by catheter laboratory. The
      first 1-year follow-up, completed on August 31, 2006, showed a low 1-year
      mortality rate (11.2%), whereby 7.6% of the patients died in hospital. There was
      a significant dependency of mortality on age, the prehospital stability of
      cardiovascular circulation, the amount of left ventricular damage, the TIMI flow
      after intervention, and the duration of interventional therapy ("puncture-to
      balloon" time). The coronary status, anticoagulation therapy as well as diabetes
      mellitus were also dependent variables, whereas the type of stent showed no
      influence. The rate of restenosis was greater with bare-metal stents (BMS)
      compared to the use of drug-eluting stents (DES). There was a low rate of
      repeated STEMI or NSTEMI (non-ST elevation myocardial infarction; 1.8%, 1.7%).
      These first long-term data confirm the successful implementation of treatment
      guidelines for STEMI patients within a standardized strategy in an urban
      environment.

PMID- 18344041
TI  - [Abstracts of the 114th Congress of the German Society of Internal Medicine,
      2008].

PMID- 18344042
TI  - Pharmacogenetics, pharmacogenomics and personalized psychiatry: are we there yet?

PMID- 18344043
TI  - Drug development in neuropsychopharmacology.
AB  - Personalized medicine is still in its infancy concerning drug development in
      neuropsychopharmacology. Adequate biomarkers with clinical relevance to drug
      response and/or tolerability and safety largely remain to be identified.
      Possibly, this kind of personalized medicine will first gain clinical relevance
      in the dementias. The clinical relevance of the genotyping of drug-metabolizing
      enzymes as suggested by drug licensing authorities for the pharmacokinetic
      evaluation of medicinal products needs to be proven in sound clinical trials.

PMID- 18344044
TI  - Refinement of diagnosis and disease classification in psychiatry.
AB  - Knowledge concerning the classification of mental disorders progressed
      substantially with the use of DSM III-IV and IDCD 10 because it was based on
      observed data, with precise definitions. These classifications a priori avoided
      to generate definitions related to etiology or treatment response. They are based
      on a categorical approach where diagnostic entities share common phenomenological
      features. Modifications proposed or discussed are related to the weak validity of
      the classification strategy described above. (a) Disorders are supposed to be
      independent but the current coexistence of two or more disorders is the rule; (b)
      They also are supposed to have stability, however anxiety disorders most of the
      time precede major depression. For GAD age at onset, family history, biology and
      symptomatology are close to those of depression. As a consequence broader
      entities such as depression-GAD spectrum, panic-phobias spectrum and OCD spectrum
      including eating disorders and pathological gambling are taken into
      consideration; (c) Diagnostic categories use thresholds to delimitate a border
      with normals. This creates "subthreshold" conditions. The relevance of such
      conditions is well documented. Measuring the presence and severity of different
      dimensions, independent from a threshold, will improve the relevance of the
      description of patients pathology. In addition, this dimensional approach will
      improve the problems posed by the mutually exclusive diagnoses (depression and
      GAD, schizophrenia and depression); (d) Some disorders are based on the
      coexistence of different dimensions. Patients may present only one set of
      symptoms and have different characteristics, evolution and response to treatment.
      An example would be negative symptoms in Schizophrenia; (e) Because no
      etiological model is available and most measures are subjective, objective
      measures (cognitive, biological) and genetics progresses created important hopes.
      None of these measures is pathognomonic and most appear to be related to risk
      factors especially at certain periods when associated with environmental events.
      One of the major aims for a classification of patients is to identify groups to
      whom a best possible therapeutic strategy can be proposed. Drugs may improve fear
      extinction while the genetic and/or acquired avoidance may be called phobia. The
      basic mechanism and or the corresponding phenotype should appear in the
      classification. Progresses in early identification of disturbances by taking into
      account all the information available (prodromal symptoms, cognitive, biological,
      imaging, genetic, family information) are crucial for the future therapeutic
      strategy: prevention.

PMID- 18344045
TI  - Contribution of allelic variations to the phenotype of response to
      antidepressants and antipsychotics.
AB  - Individualized medicine through molecular pharmacogenetics is one of the major
      future goals in clinical medicine. In psychopharmacology, pharmacogenetics became
      an expanding research component. Major research results were already attained:
      first, it is now feasible to predict a major proportion of the interindividual
      variation of plasma levels of most antidepressants and antipsychotics by using
      the DNA-sequence variation in genes for crucial CYP P450-enzymes as CYP2D6.
      Second, it is now possible to relate serious side effects (tardive dyskinesia,
      weight gain) of antipsychotics to specific genetic variants of genes for target
      proteins. Third, a long list of mainly functional variants in target protein
      genes was explored for their predictive power for the beneficial and adverse
      treatment outcome. Although specific results transferable into clinical practice
      were not yet obtained in this respect, the proof of principle could be
      demonstrated.

PMID- 18344046
TI  - Therapeutic drug monitoring in neuropsychopharmacology: does it hold its
      promises?
AB  - To produce its characteristic effects, a drug must be present in appropriate
      concentrations at its sites of action. The latter is not only a function of the
      dose administered, but also of the extent and rate of drug absorption,
      distribution, tissue binding, biotransformation, and excretion, which can vary
      markedly between individual patients due to differences in gender, age,
      morbidity, smoking or eating habits, differential expression of drug metabolising
      enzymes or drug transporters or other factors. Therefore drug concentrations in
      blood resulting after a given dose differ by tenfold or more between individual
      patients. For psychoactive drugs, animal studies have shown that plasma
      concentrations of psychotropic drugs correlate well with concentrations in the
      target organ, the brain. In the brain of patients treated with antipsychotic or
      antidepressant drugs clear-cut relationships were found between plasma
      concentrations of the drug and occupancy of dopamine receptors or serotonin
      uptake sites by positron emission tomography (PET). Monitoring concentrations of
      psychoactive drugs in plasma of patients, so called therapeutic drug monitoring
      (TDM), is therefore useful to adjust dosages for optimal "receptor" blockade. TDM
      is well established for mood stabilizers and anticonvulsant drugs. For other
      neuropsychiatric drugs, however, "routine" TDM is rare. Optimal target
      concentrations are unclear for many drugs, and the number of laboratories that
      use reliable methods to measure the low concentrations of the drugs within a
      single day is quite limited. Moreover, the use of TDM in practice is far from
      optimal. The TDM group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie
      und Pharmakopsychiatrie (AGNP see http://www.agnp.de/) has published literature
      based guidelines for optimal use of TDM in psychiatry. TDM can be most
      informative to solve problems underlying the treatment of an individual patient.
      It can be clarified if suggested non-compliance or insufficient response in spite
      of recommended doses is due to rapid metabolism of the drug. Moreover, many drug
      interactions have been detected by using TDM. In conclusion, TDM is a reliable
      tool to optimise psychopharmacotherapy. When used adequately it is helpful for
      many psychiatric patients and in many situations.

PMID- 18344047
TI  - Pharmacogenomics and therapeutic prospects in dementia.
AB  - Dementia is a major problem of health in developed countries. Alzheimer's disease
      (AD) is the main cause of dementia, accounting for 50-70% of the cases, followed
      by vascular dementia (30-40%) and mixed dementia (15-20%). Approximately 10-15%
      of direct costs in dementia are attributed to pharmacological treatment, and only
      10-20% of the patients are moderate responders to conventional anti-dementia
      drugs, with questionable cost-effectiveness. Primary pathogenic events underlying
      the dementia process include genetic factors in which more than 200 different
      genes distributed across the human genome are involved, accompanied by
      progressive cerebrovascular dysfunction and diverse environmental factors.
      Mutations in genes directly associated with the amyloid cascade (APP, PS1, PS2)
      are only present in less than 5% of the AD population; however, the presence of
      the APOE-4 allele in the apolipoprotein E (APOE) gene represents a major risk
      factor for more than 40% of patients with dementia. Genotype-phenotype
      correlation studies and functional genomics studies have revealed the association
      of specific mutations in primary loci (APP, PS1, PS2) and/or APOE-related
      polymorphic variants with the phenotypic expression of biological traits. It is
      estimated that genetics accounts for 20-95% of variability in drug disposition
      and pharmacodynamics. Recent studies indicate that the therapeutic response in AD
      is genotype-specific depending upon genes associated with AD pathogenesis and/or
      genes responsible for drug metabolism (CYPs). In monogenic-related studies, APOE
      4/4 carriers are the worst responders. In trigenic (APOE-PS1-PS2 clusters)
      related studies the best responders are those patients carrying the 331222-,
      341122-, 341222-, and 441112- genomic profiles. The worst responders in all
      genomic clusters are patients with the 441122+ genotype, indicating the powerful,
      deleterious effect of the APOE-4/4 genotype on therapeutics in networking
      activity with other AD-related genes. Cholinesterase inhibitors of current use in
      AD are metabolized via CYP-related enzymes. These drugs can interact with many
      other drugs which are substrates, inhibitors or inducers of the cytochrome P-450
      system; this interaction elicits liver toxicity and other adverse drug reactions.
      CYP2D6-related enzymes are involved in the metabolism of more than 20% of CNS
      drugs. The distribution of the CYP2D6 genotypes differentiates four major
      categories of CYP2D6-related metabolyzer types: (a) Extensive Metabolizers
      (EM)(*1/*1, *1/*10)(51.61%); (b) Intermediate Metabolizers (IM) (*1/*3, *1/*4,
      *1/*5, *1/*6, *1/*7, *10/*10, *4/*10, *6/*10, *7/*10) (32.26%); (c) Poor
      Metabolizers (PM) (*4/*4, *5/*5) (9.03%); and (d) Ultra-rapid Metabolizers (UM)
      (*1xN/*1, *1xN/*4, Dupl) (7.10%). PMs and UMs tend to show higher transaminase
      activity than EMs and IMs. EMs and IMs are the best responders, and PMs and UMs
      are the worst responders to pharmacological treatments in AD. It seems very
      plausible that the pharmacogenetic response in AD depends upon the interaction of
      genes involved in drug metabolism and genes associated with AD pathogenesis. The
      establishment of clinical protocols for the practical application of
      pharmacogenetic strategies in AD will foster important advances in drug
      development, pharmacological optimization and cost-effectiveness of drugs, and
      personalized treatments in dementia.

PMID- 18344050
TI  - Social position, early deprivation and the development of attachment.
AB  - The effects of childhood social adversity on developing parent/child attachments
      may partially explain the effects of less advantaged childhood social position on
      adulthood mental health. Associations between social position, retrospectively
      recalled parental style and childhood emotional and physical deprivation and
      attachment were examined in 7,276 civil servants from the Whitehall II Study.
      Depressive symptoms were associated with insecure attachment style. Social
      position was not associated with attachment styles. However, fathers' social
      class was strongly associated with material and emotional deprivation. In turn,
      deprivation was associated with lower parental warmth. High parental warmth was
      associated with decreased risk of insecure attachment styles. Despite the
      methodological shortcomings of retrospective childhood data the results suggest
      material and emotional adversity influence the development of attachment through
      parental style, notably parental warmth.

PMID- 18344051
TI  - Association of superficial siderosis of the central nervous system and low
      pressure headache.

PMID- 18344052
TI  - Orientation-dependent prosopagnosia.

PMID- 18344053
TI  - Acute dystonia induced by the combination of midodrine and perphenazine.

PMID- 18344054
TI  - Antibodies against disialosyl and terminal NeuNAc(alpha2-3)Gal ganglioside
      epitopes in acute relapsing sensory ataxic neuropathy.

PMID- 18344055
TI  - Severe extrapyramidal syndrome after exposition to isoamyl acetate vapour.

PMID- 18344056
TI  - CSF B--lymphocyte chemoattractant (CXCL13) in the early diagnosis of acute Lyme
      neuroborreliosis.
AB  - Recent studies have suggested a diagnostic role of the B-lymphocyte attracting
      chemokine (CXCL13) in the cerebrospinal fluid (CSF) in Lyme neuroborreliosis
      (LNB). Our aim was to evaluate diagnostic accuracy of CSF CXCL13 in a cohort of
      59 consecutive patients referred to hospital for suspected LNB. Thirty-seven
      patients were classified as definite LNB and used as the reference standard.
      Seven were classified as probable, and seven as possible LNB. Eight patients did
      not fulfil case definitions and were used as controls. At presentation, CSF
      CXCL13 was elevated in all patients with definite LNB, as compared to a positive
      CSF B. burgdorferi (Bb) antibody index (AI) in 33 of 37. Pre-treatment
      sensitivity of elevated CSF [corrected] Bb Al [corrected] was 100 % (95 % CI = 91
      100) and 89 % [corrected] (95 % CI = 75-96) respectively (p = 0.053). Among the
      eight control patients, CSF CXCL13 was normal in five and only slightly elevated
      in three, and Bb AI was negative in five. Specificity of CSF CXCL13 and Bb AI was
      similar 63 % (95 % CI = 31-86) (p = 1.0).CSF CXCL13 was elevated in 6/7 patients
      with probable LNB and 3/7 patients with possible LNB. Bb AI was negative in all
      these 14 patients. An additional control group consisted of 31 patients with
      multiple sclerosis (MS), 11 with non-inflammatory neurological diseases, and ten
      with verified non-Lyme meningitis and high CSF cell count. CSF CXCL13 was
      slightly elevated in 15 MS patients, and in nine meningitis patients. Mean CSF
      CXCL13 was higher in definite LNB (3524 ng/g CSF protein) than in MS (27 ng/g)
      and non-Lyme meningitis (23 ng/g) (p < 0.001). Four months post-treatment CSF
      CXCL13 was normalized in 82 % of patients with definite LNB, as compared to a
      negative Bb AI in 10 % (p < 0.001).CSF CXCL13 may be a useful supplement in early
      diagnosis of acute LNB.

PMID- 18344057
TI  - Clinical heterogeneity in newly diagnosed Parkinson's disease.
AB  - OBJECTIVE: To determine clinical heterogeneity in newly diagnosed Parkinson's
      disease using cluster analysis and to describe the subgroups in terms of
      impairment, disability, perceived quality of life, and use of dopaminergic
      therapy. METHODS: We conducted a k-means cluster analysis in a prospective
      hospital based cohort of 133 patients with newly diagnosed Parkinson's disease.
      Variables selected for the cluster analysis were age of disease onset, age at the
      moment of examination, rate of disease progression, levodopa responsive PD
      symptoms and levodopa non-responsive PD symptoms, cognition (mini-mental state
      examination) and emotional functioning (hospital anxiety depression scale). In
      addition, the homogeneous subgroups identified were clinically validated using
      descriptive statistics. RESULTS: Cluster analysis with a two-cluster solution
      identified a younger and older age group. The three-cluster solution identified
      an intermediate group with respect to age. In both cluster solutions the older
      the onset group, the higher the progression rate and the level of motor
      impairments. The intermediate older onset group in the three cluster solution was
      characterized by more anxiety and depressive symptoms. Increasing age at disease
      onset was significantly associated with higher Hoehn and Yahr stages, level of
      disability and lower perceived quality of life. CONCLUSIONS: We hypothesize there
      are three distinct subgroups in patients with newly diagnosed PD: a younger onset
      group, an intermediate older onset group with more anxiety and depressive
      symptoms and an oldest onset group with more motor impairment and higher rate of
      progression.

PMID- 18344058
TI  - Early detection of Fasciola gigantica infection in buffaloes by enzyme-linked
      immunosorbent assay and dot enzyme-linked immunosorbent assay.
AB  - In an attempt to develop a suitable serological test for early detection of
      Fasciola gigantica infection in buffaloes, a group of proteins were isolated from
      the somatic antigen of the parasite by immunoaffinity chromatography. The process
      of isolation of the proteins has been standardized and significant level of
      repeatability was achieved. To test the diagnostic potentiality of the antigens,
      two serological tests, viz., enzyme-linked immunosorbent assay (ELISA) and dot
      enzyme-linked immunosorbent assay, were standardized using the sera from
      experimentally noninfected (group A) and infected (group B) animals. Further, the
      sensitivity and the specificity of the tests were evaluated employing the field
      sera from animals of different parasitic load viz., F. gigantica positive (group
      C), F. gigantica and Gastrothylax crumenifer positive (group D), F. gigantica and
      Gigantocotyle explanatum positive (group E), a group of sera without F. gigantica
      but other trematode infection (group F), only G. crumenifer positive (group G),
      only G. explanatum positive (group H), G. crumenifer and G. explanatum positive
      (group I), and PM negative (group J) collected from slaughterhouses of Bareilly
      (Uttar Pradesh, India) and Patna (Bihar, India). In plate ELISA, the sensitivity
      of the antigen and the test was 75.75% while the specificity was 97%, 95%, and
      98%, respectively, against G. crumenifer, G. explanatum, and mixed infection of
      G. crumenifer and G. explanatum, respectively. In the case of dot ELISA the
      sensitivity was 86.5% and specificity was 92.3%, 94.7%, and 90%, respectively,
      against G. crumenifer, G. explanatum, and mixed infection of G. crumenifer and G.
      explanatum, respectively. The potentiality of the antigen in the diagnosis of
      field infection is discussed.

PMID- 18344059
TI  - Protective effects of pirfenidone on D-galactosamine and lipopolysaccharide
      induced acute hepatotoxicity in rats.
AB  - OBJECTIVE AND DESIGN: To investigate the protective effects of pirfenidone on
      acute liver damage caused by D-galactosamine (GalN)/lipopolysaccharide (LPS) in
      rats. MATERIAL AND TREATMENT: Sprague-Dawley rats were divided into five groups
      (five rats per group): normal control group, GalN/LPS-treated group, and three
      pirfenidone-treated group (100, 300 and 500 mg/kg i.p., respectively). All
      biochemical and histological indexes were determined at 12 h after GalN/LPS
      challenge. METHODS: Severity of liver injury was assessed by determination of
      serum ALT, AST levels and histological analysis. SOD activity and MDA
      concentrations as well as TNF-alpha and IFN-gamma levels in the liver of rats
      were measured. The expression of iNOS and its product, NO concentration were also
      determined. RESULTS: Pretreatment with pirfenidone significantly attenuated
      GalN/LPS-induced severe hepatotoxicity, as evidenced by decreased ALT, AST levels
      and MDA content and improved histopathological changes. Pirfenidone inhibited the
      elevated levels of TNF-alpha and IFN-gamma and reduced the induction of iNOS/NO
      in a dose-dependent manner, which might be important mechanisms related to its
      protective effect. CONCLUSIONS: Pirfenidone can provide a definite protective
      effect against acute hepatic injury caused by GalN/LPS in rats, which may be
      mainly mediated through its anti-inflammatory effect.

PMID- 18344060
TI  - Maximal inflammatory response benefits syngeneic skin graft acceptance.
AB  - OBJECTIVE AND DESIGN: We investigated the influence of acute inflammation in skin
      isograft acceptance. METHODS: Two mouse lines selected for maximal (AIRMAX) or
      minimal inflammatory response (AIRMIN) were transplanted with syngeneic skin.
      Cellular infiltrates and cytokine production were measured 1, 3, 7 or 14 days
      post-transplantation. The percentage of CD4+CD25+Foxp3+ cells in the lymph nodes
      was also evaluated. RESULTS: Grafts were totally accepted in 100% of AIRMAX and
      in 26% of AIRMIN mice. In the latter, partial acceptance was observed in 74% of
      the animals. Emigrated cells were basically PMN and were enhanced in AIRMAX
      transplants. IL-10 production by graft infiltrating cells showed no interline
      differences. IFN-gamma was increased in AIRMIN grafts at day 14 and lower
      percentages of CD4+CD25+Foxp3+ cells in the lymph nodes were observed in these
      mice. CONCLUSIONS: Our data suggest that differences in graft acceptance might be
      due to a lack of appropriate regulation of the inflammatory response in AIRMIN
      mice compromising the self/non-self recognition.

PMID- 18344061
TI  - Delayed enhancement cardiac magnetic resonance imaging reveals typical patterns
      of myocardial injury in patients with various forms of non-ischemic heart
      disease.
AB  - BACKGROUND: Late gadolinium-hyperenhancement (LHE) on cardiac magnetic resonance
      imaging (CMR) has been linked to cardiovascular risk in ischemic and non-ischemic
      heart disease. We aimed to systematically categorize LHE-patterns in a variety of
      non-ischemic heart diseases (NIHD) and to explore their relationship with left
      ventricular (LV) function. METHODS: In a retrospective database search, 156
      patients with NIHD who exhibited LHE on CMR were identified. All images were re
      analyzed stepwise. LHE was correlated to LV functional parameters. Cardiac
      magnetic resonance (CMR) was conducted on 1.5 T scanners. RESULTS: Typically, LHE
      spared the subendocardium. Consistent LHE-patterns were observed in myocarditis,
      hypertrophic and dilated cardiomyopathy and systemic vasculitis. No conclusive
      LHE-patterns were observed in patients with aortic stenosis, arterial
      hypertension, lupus erythematosus, sarcoidosis, ventricular arrhythmia and in a
      mixed subgroup of rare NIHDs. There was no significant relationship between LHE
      and ejection fraction. There was no correlation between enddiastolic volume and
      LHE in either myocarditis (P = 0.13) or dilated cardiomyopathy (P = 0.62). LHE
      was unrelated to LV-mass in aortic stenosis (P = 0.13) and hypertrophic
      cardiomyopathy (P = 0.38). CONCLUSIONS: Distinct LHE patterns exist in various
      NIHDs and their visualization may ultimately aid diagnosis. Unlike in ischemic
      heart disease, the structure-function relationship does not appear to be strong.

PMID- 18344062
TI  - [The problem of rare diseases: a challenge for teaching, research and patient
      care].

PMID- 18344063
TI  - [Congenital heart disease in adulthood].
AB  - While a few decades ago only a minority of patients, particularly of those with
      complex congenital heart disease, could reach adulthood, progress of pediatric
      cardiology and cardiac surgery allows now the survival of the majority. Thus,
      adult cardiology is faced with a new challenging patient population. Since only a
      few congenital heart defects can be cured, regular follow-up during adult life is
      of major importance. Residual as well as consequently developed lesions must be
      recognized. Optimal timing of surgery or catheter intervention is necessary to
      provide the best long-term outcome. Despite optimal treatment part of the
      patients will develop long-term complications such as arrhythmias, pulmonary
      hypertension and, eventually, heart failure. Acute complications such as
      arrhythmias, aortic dissection or rupture, endocarditis, cerebral events due to
      embolism, bleeding or abscesses, and pulmonary embolism or bleeding must be
      recognized early and treated appropriately. Management of noncardiac surgery,
      pregnancy and delivery can be challenging. Another task is counseling regarding
      exercise and sports, choice of profession, driving and insurance issues. Finally,
      psychosocial issues must be taken into account for appropriate care of this
      special patient group.

PMID- 18344064
TI  - [Adamantiades-Behcet's disease. Clinical review].
AB  - Behcet's disease is a chronic relapsing systemic vasculitis of unknown etiology,
      affecting predominantly oral and genital mucocutaneous tissues and also the eyes.
      The disease is spread worldwide with a higher prevalence rate in countries along
      the ancient Silk Route, but it is rare (1-10/100,000) in Central and Northern
      Europe. Genetic, environmental, immunologic, inflammatory and rheologic factors
      are involved in the pathogenesis and the course of the disease. Any vascularized
      organ may be affected. Eye involvement is frequent, and may eventually result in
      loss of vision. Further important complications are cerebral manifestations,
      thrombotic syndromes, and arterial aneurysms with a high risk of rupture.
      Diagnosis and therapy of Behcet's disease are best managed by an
      interdisciplinary team. Skin lesions may be controlled by systemic treatment with
      colchicine, alternatively with dapsone, and in severe cases with thalidomide.
      Active systemic disease should be treated more aggressively using
      immunosuppressants. Despite advances in treatment relapses are still frequent,
      and systemic disease remains associated with an adverse prognosis.

PMID- 18344065
TI  - [Cardiac amyloidosis].
AB  - Amyloidoses are a heterogeneous group of multisystem disorders, which are
      characterized by an extracellular deposition of amyloid fibrils. Typically
      affected are the heart, liver, kidneys, and nervous system. More than half of the
      patients die due to cardiac involvement. Clinical signs of cardiac amyloidosis
      are edema of the lower limbs, hepatomegaly, ascites and elevated jugular vein
      pressure, frequently in combination with dyspnea. There can also be chest pain,
      probably due to microvessel disease. Dysfunction of the autonomous nervous system
      or arrhythmias may cause low blood pressure, dizziness, or recurrent syncope. The
      AL amyloidosis caused by the deposition of immunoglobulin light chains is the
      most common form. It can be performed by monoclonal gammopathy. The desirable
      treatment therapy consists of high-dose melphalan therapy twice followed by
      autologous stem cell transplantation. Due to the high peritransplantation
      mortality, selection of appropriate patients is mandatory. The ATTR amyloidosis
      is an autosomal dominant disorder caused by the amyloidogenic form of
      transthyretin, a plasmaprotein that is synthesized in the liver. Therefore, liver
      transplantation is the only curative therapy. The symptomatic treatment of
      cardiac amyloidosis is based on the current guidelines for chronic heart failure
      according to the patient's New York Heart Association (NYHA) state. Further types
      of amyloidosis with possible cardiac involvement comprise the senile systemic
      amyloidosis caused by the wild-type transthyretin, secondary amyloidosis after
      chronic systemic inflammation, and the beta(2)-microglobulin amyloidosis after
      long-term dialysis treatment.

PMID- 18344066
TI  - [Cardiac involvement in Fabry's disease].
AB  - Fabry's disease is a rare X-linked lysosomal storage disorder leading to an
      accumulation of globotriaosylceramides in the lysosomes of all tissues. The
      disease is characterized by a progressive involvement of important vital organs
      like the kidneys, the cerebrovascular system and the heart. Within the scope of
      this article an overview of Fabry's cardiomyopathy, the necessary cardiac
      diagnostic tests and, in addition, the new concept of enzyme replacement therapy
      is given.

PMID- 18344067
TI  - [Monogenic heart disease].
AB  - The pathogenesis of most cardiovascular disorders is multifactorial and
      incompletely understood. Besides genetic influences that often arise from
      multiple genetic loci, the specific nutritional and environmental influences do
      contribute to the dysfunctional development. Nevertheless, a rather small number
      of cardiovascular diseases exhibits Mendelian traits, since they are caused by a
      single gene defect. Examples are familial cardiomyopathies, primary arrhythmias
      and connective tissues disorders of vessels. More detailed investigations reveal
      that even these entities are usually not purely monogenic, as they do not appear
      with the same intensity in all mutation carriers. Hence, there must be further
      modifying factors that influence the penetrance of the disease. Despite this
      limitation monogenic diseases allow the identification of the underlying genetic
      defects and thereby a deeper insight into the pathophysiology. Predictive genetic
      diagnostics, on the other hand, permit a better adaptation of medical care to the
      individual risk of offspring that are not yet affected.

PMID- 18344068
TI  - [Cardiac tumors--clinical symptoms, diagnostic approaches, and therapeutic
      aspects].
AB  - Cardiac tumors are rare; however, they pose diagnostic and therapeutic challenges
      on the physician and, in most cases, interdisciplinary approaches are necessary.
      The present article summarizes the most frequent cardiac tumors and discusses the
      diagnostic aspects and therapeutic consequences. The focus of this article is on
      primary cardiac tumors.

PMID- 18344069
TI  - LC-MS-MS identification of albendazole and flubendazole metabolites formed ex
      vivo by Haemonchus contortus.
AB  - Resistance of helminth parasites to common anthelminthics is a problem of
      increasing importance. The full mechanism of resistance development is still not
      thoroughly elucidated. There is also limited information about helminth enzymes
      involved in metabolism of anthelminthics. Identification of the metabolites
      formed by parasitic helminths can serve to specify which enzymes take part in
      biotransformation of anthelminthics and may participate in resistance
      development. The aim of our work was to identify the metabolic pathways of the
      anthelminthic drugs albendazole (ABZ) and flubendazole (FLU) in Haemonchus
      contortus, a world-wide distributed helminth parasite of ruminants. ABZ and FLU
      are benzimidazole anthelminthics commonly used in parasitoses treatment. In our
      ex vivo study one hundred living adults of H. contortus, obtained from the
      abomasum of an experimentally infected lamb, were incubated in 5 mL RPMI-1640
      medium with 10 micromol L(-1) benzimidazole drug (10% CO(2), 38 degrees C) for 24
      h. The parasite bodies were then removed from the medium. After homogenization of
      the parasites, both parasite homogenates and medium from the incubation were
      separately extracted using solid-phase extraction. The extracts were analyzed by
      liquid chromatography-mass spectrometry (LC-MS) with electrospray ionization
      (ESI) in positive-ion mode. The acquired data showed that H. contortus can
      metabolize ABZ via sulfoxidation and FLU via reduction of a carbonyl group.
      Albendazole sulfoxide (ABZSO) and reduced flubendazole (FLUR) were the only phase
      I metabolites detected. Concerning phase II of biotransformation, the formation
      of glucose conjugates of ABZ, FLU, and FLUR was observed. All metabolites
      mentioned were found in both parasite homogenates and medium from the incubation.

PMID- 18344070
TI  - Solid-phase microextraction for the gas chromatography mass spectrometric
      determination of oxazole fungicides in malt beverages.
AB  - This paper describes a method for the sensitive, selective, and solvent-free
      determination of six oxazole fungicide residues (hymexazol, drazoxolon,
      vinclozolin, chlozolinate, oxadixyl, and famoxadone) in malt beverages. Direct
      immersion solid-phase microextraction (DI-SPME) coupled to gas chromatography
      with mass spectrometry in the selected ion monitoring mode, GC-MS(SIM), is used.
      A comparison of the optimal fiber used, a polar carbowax-divinylbenzene 70-microm
      fiber, and a nonpolar polydimethylsiloxane 100-microm fiber was carried out.
      Optimal extraction conditions were 60 degrees C and an extraction time of 30 min
      under continuous stirring. Desorption was carried out at 250 degrees C for 5 min.
      Detection limits ranged from 0.006 to 0.3 microg L(-1) at a signal to noise ratio
      of 3, depending on the compound. The proposed method was successfully applied to
      malt beverages including malt, beer, and whisky, and none of the samples
      contained residues higher than detection limits.

PMID- 18344071
TI  - Aedes aegypti (Diptera: Culicidae): monitoring of populations to improve control
      strategies in Argentina.
AB  - To study the seasonal fluctuations of populations of Aedes aegypti (L.), to
      improve control strategies, or to monitor chemical control interventions, a
      lightweight, inexpensive ovitrap made of black plastic, pail-shaped, stackable,
      and provided with a wood tongue depressor was used. Field assays were performed
      in the northeast and northwest part of Argentina. In a 1-year trial performed in
      Tartagal (Salta), almost 100% of the ovitraps were highly positive, collecting a
      total of 1,000/2,000 eggs during March and the first part of April. A focal
      treatment in the corresponding neighborhood, performed at this time, immediately
      began to reduce positive ovitraps in spite of the high temperatures registered,
      rising again in November after winter season. Another field trial was performed
      in the whole urban area of Iguazu (Misiones). Mosquito populations were evaluated
      after three weekly ultra low volume (ULV) applications with an EC formulation of
      permethrin in water. The number of positive ovitraps diminished from 49% to 10%
      after the treatments. The last one performed in Wanda (Misiones) showed that
      positive ovitraps inside the dwellings aided in determining reinfestation rates
      after an intervention with a smoke-generating formulation containing beta
      cypermethrin. The work performed in three different situations in urban areas at
      high risk of dengue can be considered a preliminary assay to establish the
      effective performance of simple ovitraps, allowing the Vector Control Service of
      the Argentinian Ministry of Health its use to improve surveillance and control
      strategies.

PMID- 18344072
TI  - Candida alocasiicola sp. nov., Candida hainanensis sp. nov., Candida heveicola
      sp. nov. and Candida musiphila sp. nov., novel anamorphic, ascomycetous yeast
      species isolated from plants.
AB  - In a taxonomic study on the ascomycetous yeasts isolated from plant materials
      collected in tropical forests in Yunnan and Hainan Provinces, southern China,
      four strains isolated from tree sap (YJ2E(T)) and flowers (YF9E(T), YWZH3C(T) and
      YYF2A(T)) were revealed to represent four undescribed yeast species. Molecular
      phylogenetic analysis based on the large subunit (26S) rRNA gene D1/D2 domain
      sequences showed that strain YJ2E(T) was located in a clade together with Candida
      haemulonii and C. pseudohaemulonii. Strain YF9E(T) was most closely related to C.
      azyma and strain YWZH3C(T) to C. sorbophila and C. spandovensis. Strain YYF2A(T)
      was clustered in a clade containing small-spored Metschnikowia species and
      related anamorphic Candida species. The new strains differed from their closely
      related described species by more than 10% mismatches in the D1/D2 domain. No
      sexual states were observed for the four strains on various sporulation media.
      The new species are therefore assigned to the genus Candida and described as
      Candida alocasiicola sp. nov. (type strain, YF9E(T) = AS 2.3484(T) = CBS
      10702(T)), Candida hainanensis sp. nov. (type strain, YYF2A(T) = AS 2.3478(T) =
      CBS 10696(T)), Candida heveicola sp. nov. (type strain, YJ2E(T) = AS 2.3483(T) =
      CBS 10701(T)) and Candida musiphila sp. nov. (type strain, YWZH3C(T) = AS
      2.3479(T) = CBS 10697(T)).

PMID- 18344073
TI  - Determination of particulate-bound formaldehyde from burning incense by solid
      phase microextraction.
AB  - This work studied the feasibility of using a solid phase microextraction (SPME)
      fiber for sampling and analysis of gaseous formaldehyde as well as particulate
      bound formaldehyde from burning Chinese incense. The SPME fiber with PDMS/DVB
      coating were partially coated with o-(2,3,4,5,6-pentafluorobenzyl)-hydroxylamine
      hydrochloride (PFBHA), and used for sampling formaldehyde. The sampling rate for
      formaldehyde and its dependence on temperature, relative humidity and sampling
      time were observed. The same PFBHA treated fibers were, in parallel, exposed to
      incense burning smoke with pre-filtration and without pre- filtration for 0.5-1
      min. The NIOSH method 2541 using an XAD-2 tube at a flow rate of 0.1 Lpm was also
      applied for sampling simultaneously. The results demonstrate that commercially
      available PDMS/DVB fibers partially coated with PFBHA are capable of sampling the
      gas phase of formaldehyde as well as particulate-bound formaldehyde. The
      determined level of formaldehyde was close to the result obtained by the NIOSH
      method 2541. However, a reduction of the fiber's formaldehyde loading capacity in
      the aerosol sampling in comparison with gas sampling was noticed. This indicates
      that the particulate characteristics, and their bound chemicals other than
      formaldehyde may influence the maximum loading capacity of formaldehyde, and some
      characteristic particulates in high concentrations may even deteriorate the fiber
      coating.

PMID- 18344074
TI  - Relationship between the evaporation rate and vapor pressure of moderately and
      highly volatile chemicals.
AB  - Volatilization of chemicals can be an important form of dissipation in the
      environment. Rates of evaporative losses from plant and soil surfaces are useful
      for estimating the potential for food-related dietary residues and operator and
      bystander exposure, and can be used as source functions for screening models that
      predict off-site movement of volatile materials. A regression of evaporation on
      vapor pressure from three datasets containing 82 pesticidal active ingredients
      and co-formulants, ranging in vapor pressure from 0.0001 to >30,000 Pa was
      developed for this purpose with a regression correlation coefficient of 0.98.

PMID- 18344075
TI  - [Preoperative chemoradiotherapy with FOLFOX in low rectal cancer: a multicenter
      study].
AB  - OBJECTIVE: To investigate the toxicity and safety of FOLFOX regimen concurrent
      with radiotherapy in neoadjuvant setting in patients with low rectal cancer.
      METHODS: Fifty-six patients with stage T(3-4)N(0)M(0) and T(1-4)N(1-2)M(0) were
      eligible from Aug. 2004 to Jul. 2007. Upon entry the study, they received 4
      cycles of chemotherapy with FOLFOX regimen. Radiotherapy was added from the
      second cycle of chemotherapy (CT). The total dose of radiotherapy (RT) was 46 Gy
      (2 Gy x 23). Total mesorectal excision (TME) was performed 4-8 weeks after RT.
      RESULTS: Among them, 54 cases received 4 cycles of CT, 1 patient stopped CT after
      the second cycle of CT because of unrecovery from neutropenia. One patient
      stopped chemoradiotherapy(CRT) because of complicating with active pulmonary
      tuberculosis after 2 cycles of CT and 10 times of RT. Two occurred liver, lung
      and bone metastases after CT. Totally 220 cycles of CT were administrated. Fifty
      two patients received operation after CRT, 50 with anal interior sphincter
      reservation, 19 with prophylactic ileac stoma. Anastomotic leakage occurred in 2
      patients after operation, and rectal vaginal fistula in 2 patients 1 month after
      operation. According to the pathologic results, 7 patients achieved complete
      response, 41 partial response, 4 stable disease, and the objective response rate
      was 85.7%. CONCLUSION: Concomitant treatment of FOLFOX regimen and RT in
      neoadjuvant setting of rectal cancer was safe and tolerable, and it suggests that
      protective ileostomy for anastomotic leakage following anus-preserving operation
      should be performed.

PMID- 18344076
TI  - [Cost-effectiveness analysis of different chemotherapeutical regimens in
      metastatic colorectal cancer].
AB  - OBJECTIVE: To compare FOLFOX6 and FOLFIRI regimen in the treatment of metastatic
      colorectal cancer with cost-effective analysis. METHODS: Cost-effective analysis
      was conducted based on the efficacy results of V308 clinical trial of FOLFOX6 and
      FOLFIRI regimen and the medical system price in Zhongshan hospital. RESULTS: The
      minimal cost analysis showed FOLFIRI followed by FOLFOX6 had the cost of RMB
      206365.78 Yuan for each patient during the whole treatment period, and RMB
      170468.89 Yuan for the FOLFOX6 followed by FOLFIRI regimen. Incremental analysis
      showed FOLFIRI followed by FOLFOX6 regimen could prolong one month of overall
      survival with additional cost of RMB 39885.44 Yuan in each patient while compared
      with the regimen of FOLFOX6 followed by FOLFIRI. CONCLUSIONS: Both FOLFOX and
      FOLFIRI regimens are able to prolong the survival time of patients with
      metastatic colorectal cancer, but cost of such treatments are still quite
      expensive for Chinese patients. FOLFOX6 regimen suggests better cost
      effectiveness than FOLFIRI.

PMID- 18344077
TI  - [Efficacy comparison of neoadjuvant radiotherapy with or without chemotherapy for
      locally advanced rectal cancer].
AB  - OBJECTIVE: To evaluate the efficacy of neoadjuvant radiotherapy alone versus
      chemoradiotherapy in patients with mid-low locally advanced rectal cancer.
      METHODS: Data of 69 patients with advanced (stage T(3) or T(4)) rectal cancer,
      undergone neoadjuvant therapy in our hospital from October 1997 to October 2007,
      were analyzed retrospectively. Forty patients received preoperative radiotherapy
      (50 Gy in 25 fractions over 5 weeks) alone (RT group), and 29 patients received
      preoperative radiotherapy concomitant with 5-FU/leucovorin -based preoperative
      chemoradiotherapy (CRT group). Radical surgery was performed 4-6 weeks after
      radiation therapy by the rule of TME. RESULTS: All the patients underwent
      operations, including 26 abdominoperineal resections, 27 anterior resections, 10
      Parks operations and 6 Hartmann's procedures. The sphincter preservation rate was
      47.5%(19/40) in RT group, and 62.1%(18/29) in CRT group(P>0.05). In pathological
      findings, tumor and nodal downstaging were observed in 12 patients of RT group
      (30.0%), and 17 of CRT group (58.6%)(P<0.05). In RT group, 3 patients (7.5%)
      showed pathological complete regression (pCR), and the overall response rate (CR
      plus PR) was 60%(24/40). In CRT group, 4(13.8%) showed pCR and the overall
      response rate was 79.3%(23/29). There was significant difference of the overall
      response rate between two groups. Three-year disease-free survival for all
      patients was 77.3%. CONCLUSION: For patients with locally advanced rectal cancer,
      neoadjuvant chemoradiotherapy provides higher sphincter preservation rate,
      overall response rate and better down-staging as compared to radiotherapy alone.

PMID- 18344078
TI  - [Study on retrograde metastasis rule of middle-low rectal cancer].
AB  - OBJECTIVE: To investigate the resection range of mesorectum and rectum below the
      inferior margin of tumor for the total mesorectum excision (TME) in middle-low
      rectal cancer. METHODS: Sixty patients were enrolled in the study. After TME
      operation, serial 5 mm interval sections were made in specimens of middle-low
      rectal cancer. The retrograde metastasis of rectal cancer was observed by routine
      HE staining. RESULTS: The phenomena of retrograde metastasis in mesorectum were
      found in 15 cases, and the distance of retrograde metastasis was 0.5-4.0(2.47+/
      1.06) cm, which was correlated with Dukes stage, lymph node metastasis and
      histological differentiation. The retrograde metastases in bowel were found in 11
      cases, and the distance of retrograde metastasis was 0.5-4.0 (1.64+/-1.16) cm,
      which was correlated with histological differentiation. CONCLUSIONS: The distal
      mesorectum should be resected at least 4 cm when TME is carried out, and the
      distal bowel at least 2.5 cm. More than 5 cm mesorectum and bowel should be
      resected when advanced Dukes stage, extensive lymph node metastasis and poor
      histological differentiation occurred.

PMID- 18344079
TI  - [Evaluation of the preoperative staging of rectal cancer by magnetic resonance
      imaging].
AB  - OBJECTIVE: To evaluate the value of MRI in preoperative staging of rectal cancer.
      METHODS: The data of 156 rectal cancer patients,undergone MRI scans from December
      2004 to June 2006 in our hospital, were analyzed retrospectively. Findings of MRI
      were compared with postoperative pathological examinations. RESULTS:
      Intracavitary localized parenchyma tumors were seen in 72 cases, and intestinal
      wall abnormal incrassation or stricture in other 84 cases from MRI scan. Sixteen
      cases had rectal polyps simultaneously, 2 cases ovarian cysts, 13 cases anterior
      sacral metastases and 2 cases bone metastases. The sensitivity and specificity of
      T(1-2), T(3) and T(4) rectal cancer by MRI examination were 25%(8/32),
      93.3%(84/90), 94.1%(32/34) and 100%(124/124), 57.6%(38/66), 96.7%(118/122)
      respectively. In MRI imaging, metastatic para-rectal lymph node was diagnosed as
      the diameter >5 mm or abnormal border or mixed resonance, with a sensitivity of
      85.1%(80/94) and specificity of 45.2%(28/62). CONCLUSION: MRI has high accuracy
      for preoperative staging of rectal cancer, and is useful to detect the serosal
      infiltration and lymph node metastasis.

PMID- 18344080
TI  - [Clinical significance of lymphatic vessel density in determining the length of
      distal resection in rectal cancer].
AB  - OBJECTIVE: To study the the relationship between lymphatic vessel density (LVD)
      and distal intramural spread (DIS), and evaluate the value of LVD in determining
      the length of distal resection in low rectal cancer. METHODS: Ninety-two samples
      from patients undergone curative resection of low rectal cancer were studied. DIS
      was detected by HE stain. LVD was examined by immunohisto-chemical LYVE-1
      (lymphatic vessel endothelial hyaluronan receptor). The association of LVD with
      DIS and other clinicopathological factors were examined. RESULTS: DIS (range 0.1
      2.4 cm, mean 0.31 cm) was present in 44(47.8%) patients with low rectal cancer,
      including 23(52.3%) cases with cancer emboli in lymphatic vessels. LVD of
      peritumoral lesion was significantly higher than that of intratumoral lesion. LVD
      of DIS subgroup was significantly higher than that of non-DIS subgroup. Positive
      correlation was found by rank correlation test between the length of DIS and the
      LVD at peritumor tissue in DIS group (n=44, r=0.755, P<0.01). LVD was also
      positively correlated with the infiltration extent, lymphatic invasion and lymph
      node metastasis. CONCLUSIONS: Lymphangiogenesis plays an important role in rectal
      cancer metastasis and cancer emboli in lymphatic vessels is the most common
      modality of DIS. The LVD is positively correlated with DIS, which may be helpful
      to determine the distal clearance length of rectal cancer.

PMID- 18344081
TI  - [A comparison of the metabolic effect of postoperative analgesia with lornoxicam
      and morphine or morphine on patients undergoing gastrointestinal carcinoma
      operation].
AB  - OBJECTIVE: To compare the metabolic effect of postoperative analgesia with
      lornoxicam/morphine or morphine on patients undergoing gastrointestinal carcinoma
      operation. METHODS: One hundred patients, undergone gastrointestinal carcinoma
      operations, were randomly assigned into two groups: group A received
      postoperative analgesia with lornoxicam/morphine and Group B with morphine alone.
      Parenteral nutrition with limited nitrogen resource was given to both groups.
      Visual analog scale (VAS), temperature and postoperative nitrogen balance were
      monitored postoperatively. The concentration of plasma cortisol , epinephrine,
      tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured
      preoperatively and day 1, 3 postoperatively. RESULTS: VAS of two groups at 24 th,
      48 th, 72 th after operation were similar (P>0.05). The temperature of two groups
      on the third postoperative day increased as compared to that before operation,
      and the temperature of group B on 1st and 3rd postoperative day [(37.8+/
      0.6),(37.5+/-0.8)degrees C] were significantly higher than those of group
      A[(37.3+/-0.5)degrees C,(37.0+/-0.8)degrees C](P<0.05). Nitrogen balance within 3
      days after operation were -7.5+/-3.2, -5.2+/-4.2, -3.1+/-1.2 in group A and 
      16.7+/-7.3, -10.5+/-6.1, -9.1+/-2.1 in group B (P<0.05). The post-operative
      plasma concentrations of cortisol and epinephrine increased significantly in both
      groups as compared to those examined preoperatively(P<0.05), but there was no
      significant difference between the two groups. However, the plasma concentrations
      of TNF-alpha and IL-6 in group B were significantly higher than those in group
      A(P<0.05). CONCLUSIONS: Postoperative analgesia with lornoxicam/morphine or
      morphine is able to produce an adequate postoperative analgesia to patients
      undergoing gastrointestinal carcinoma operation. Lornoxicam and morphine
      analgesia possesses a better metabolic intervention in decreasing the protein
      metabolism and improving the nitrogen balance.

PMID- 18344082
TI  - [Prognostic analysis of liver metastasis in gastric cancer patients with radical
      gastrectomy].
AB  - OBJECTIVE: To elucidate the prognostic factors of liver metastasis in gastric
      cancer patients with radical gastrectomy. METHODS: Clinicopathological data of 87
      liver metastasis patients, undergone radical gastrectomy for gastric cancer from
      1996 to 2001, were retrospectively analyzed. RESULTS: Of these 87 patients, the 1
      , 3- and 5-year survival rates were 28.8%, 3.6% and 0 respectively and the
      average survival time after gastrectomy was (11.3+/-1.1) months. By univariate
      analysis, tumor location, tumor size, histologic differentiation, invasive depth,
      Lauren classification, metastasis of lymph nodes from lymphadenectomy, vascular
      invasion, nervous invasion, peritoneal metastasis, number of liver metastasis,
      liver metastatic distribution and resection of liver metastasis were found to be
      significant factors associated with the prognosis of liver metastatic patients
      after radical gastrectomy. By multivariate analysis, location, the Lauren
      classification, liver metastatic distribution and resection of liver metastasis
      were found to be independent factors associated with hepatic metastasis after
      radical gastrectomy. CONCLUSION: Location of gastric cancer, Lauren
      classification, liver metastatic distribution and resection of liver metastasis
      are important factors to evaluate the prognosis of liver metastasis in gastric
      cancer patients with radical gastrectomy.

PMID- 18344083
TI  - [Diagnostic value of endoscopic ultrasonography and CT in T, N stage of
      preoperative esophageal cancer].
AB  - OBJECTIVE: To evaluate the preoperative endoscopic ultrasonography (EUS) and CT
      in the diagnosis of TN stage of esophageal cancer. METHODS: Fifty-one
      hospitalized patients with esophageal cancer in our center from July 2002 to
      January 2004 were enrolled in this study. According to UICC (1997) TNM clinical
      stage, the TN stage results of esophageal cancer by EUS and CT examination of
      above 51 cases were compared with the postoperative pathological TN stage.
      RESULTS: (1)The accuracy rates of T and N stage by EUS were 82.4%(42/51) and
      88.0%(45/51) respectively. The accuracy rates of T and N stage by CT were
      52.9%(27/51) and 51.0%(26/51) respectively. The accuracy rates of T and N stage
      by combination of EUS and CT were 86.3%(44/51) and 90.0%(46/51). (2)The
      consistent condition among EUS, CT or combination of EUS and CT with pathology:
      The Kappa of EUS to T and N stage were 0.700(P<0.001) and 0.763(P<0.001). The
      Kappa of CT to T and N stage were 0.275(P=0.002) and 0.006(P=0.964). The Kappa of
      EUS+CT to T and N stage were 0.769(P<0.001) and 0.801(P<0.001). (3)Significant
      differences were found between EUS and CT:PT=0.001(chi(2)=10.079) and
      PN<0.001(chi(2)=16.730). No significant difference was found between EUS+CT and
      EUS. CONCLUSIONS: EUS can be used as important and main preoperative examination
      because of presenting high accuracy rate in the diagnosis of T and N stage of
      esophageal cancer. EUS+CT does not improve accuracy rate significantly in TN
      stage diagnosis of esophageal cancer.

PMID- 18344084
TI  - [Expression and intracellular localization of FRZB gene in gastric cancer and its
      significance].
AB  - OBJECTIVE: To study the expression and intracellular localization of FRZB gene in
      gastric cancer tissue, and to explore its significance in gastric cancer.
      METHODS: The expression of FRZB in tumor tissues from 90 patients with gastric
      cancer and in normal gastric mucous as control were analyzed by
      immunohistochemistry in tissue array. FRZB expression in gastric cancer cell
      lines and immortalized gastric epithelial cell line GES-1 were detected by
      quantitative real-time PCR(Q-PCR) and Western blot. The intracellular
      localization of FRZB was observed by immunofluorescence staining. RESULTS: The
      positive expression rate of FRZB in gastric cancer was 92.2%. FRZB expressed in
      gastric cancer with well differentiation was higher than that with poor
      differentiation.The positive rate in normal gastric mucous was 10.0% (one out of
      ten). By confocal microscope, FRZB localized both in cytoplasma and nucleus,
      especially on the nuclear membrane. The Q-PCR and Western blot results also
      showed that the expression of FRZB in gastric cancer cell lines was higher than
      that in GES-1. CONCLUSIONS: The expression of FRZB in gastric cancer is
      correlated with tumor cell differentiation and tumor Lauren classification. The
      nuclear localization of FRZB may contribute to its function in gastric cancer
      formation and progression.

PMID- 18344085
TI  - [Study on the mechanism of DDP-resistance mediated by phosphate JNK in gastric
      cancer].
AB  - OBJECTIVE: To investigate the mechanism of DDP-resistance in gastric cancer cell
      line SGC7901/DDP mediated by phosphate(p)-JNK. METHODS: The p-JNK expression was
      blocked by the JNK inhibitor SP600125. The drug sensitivity was detected by MTT.
      Cell apoptosis rate was measured by flow cytometry. The expression of p-JNK and P
      glycoprotein (P-gp) was examined by Western blot. The expression of both proteins
      were detected in a tissue microarray containing 168 spots of cancer tissue and 27
      spots of normal gastric tissue by SP immunohistochemistry. Pearson method was
      used to analyze the correlation between p-JNK and P-gp. RESULTS: The drug
      sensitivity and cell apoptosis rate significantly increased (P<0.01), and the
      protein expression levels of p-JNK and P-glycoprotein were down-regulated after
      the inhibition of p-JNK by SP600125 in both SGC7901(p-JNK: 1.17+/-0.03 vs 0.38+/
      0.071, P-gp: 0.21+/-0.01 vs 0.06+/-0.01) and SGC7901/DDP (p-JNK: 2.56+/-0.14 vs
      1.02+/-0.12, P-gp: 0.77+/-0.05 vs 0.52+/-0.06 )cells(all P<0.01). The protein
      expression rates of p-JNK and P-glycoprotein were 45.8% and 51.8% respectively in
      gastric cancer tissue, which were significantly higher than those in normal
      gastric tissue 7.4% and 18.5% (P<0.01). The correlation of protein expression of
      p-JNK and P-gp was positive (P<0.01). CONCLUSION: JNK anti-apoptosis pathway with
      the regulation of P-gp expression plays an important role in the DDP-resistance
      of gastric cancer, which may be a novel target for reversing multidrug
      resistance.

PMID- 18344086
TI  - [Protein expression and clinical significance of cyclooxygenase 2 and nuclear
      factor kappa B in gastric mucosa-associated lymphoid tissue lymphoma].
AB  - OBJECTIVE: To investigate the protein expression of cyclooxygenase 2 (COX-2) and
      nuclear factor kappa B (NF-kappaB) in gastric mucosa-associated lymphoid tissue
      (MALT) lymphoma and its clinical significance. METHODS: Protein expression of COX
      2 and NF-kappaB in gastric MALT lymphoma were examined by immunohistochemistry of
      Envision two-step method. The correlations of COX-2 and NF-kappaB expression with
      Helicobacter pylori (Hp) infection, clinical stage, depth of tumor invasion,
      tumor size, recurrent rate and treatment were analyzed by univariate,
      multivariate and Pearson analysis. RESULTS: The positive expression of COX-2 and
      NF-kappaB in gastric MALT lymphoma were 48.9%(23/47) and 36.2% (17/47)
      respectively, and a positive correlation was found between these two
      factors(r=0.326,P<0.05). Moreover, COX-2 expression was positively correlated
      with Hp infection,clinical stage, depth of invasion and tumor size (P<0.05).
      Univariate analysis showed that the overall survival of gastric MALT lymphoma
      patients with positive COX-2 protein (59.9 months) was shorter than that of
      patients with negative COX-2 protein (77.8 months), but the difference was not
      significant (P>0.05). The survival was significantly shorter in gastric MALT
      lymphoma patients with positive NF-kappaB protein (26 months) than that of
      patients with negative NF-kappaB protein (123.2 months)(P<0.05). Multivariate Cox
      regression analysis revealed that clinicopathological stage was independent
      prognostic factor, and associated with short survival. CONCLUSION: Up-regulated
      expression of COX-2 and activation of NF-kappaB are associated with Hp infection
      in gastric MALT lymphoma, and their protein expression is correlated with the
      development of tumor and prognosis.

PMID- 18344087
TI  - [Prognostic value of cyclin E and its relation to blood vessel invasion in rectal
      cancer].
AB  - OBJECTIVE: To investigate the expression of cyclin E in rectal carcinoma and its
      prognostic significance. METHODS: Cyclin E expression was examined by Western
      blotting in tumor tissue samples from 130 potentially resected rectal cancer
      patients with pathological stages I- III. Blood vessel invasion (BVI) was
      detected by immunohistochemistry. Multivariate analysis using the COX
      proportional hazards models was applied to evaluate the independent prognostic
      tumor markers of rectal cancer. RESULTS: The high expression rate of cyclin E in
      rectal carcinoma tissue was 23.1%(30/130). Except for a positive correlation with
      BVI and the gross configuration of tumor, the expression of cyclin E showed no
      significant relation to other clinicopathological factors. The 5-year disease
      specific survival rate of cyclin E high expression group was 29.2%, which was
      significantly lower as compared to that of cyclin low expression group 70.5%
      (P<0.05). Multivariate analysis revealed that histology and cyclin E expression
      were independent prognostic indicators for rectal cancer patients at stages I-
      III. Compared to those with low expression levels, patients with high cyclin E
      levels had the hazard ratio (95%CI) for death from rectal cancer for 3.544 (1.528
      8.215). In stage I- II, multivariate analysis showed that stronger predictive
      values of cyclin E expression even were detected. Patients with low cyclin E
      expression and negative BVI had a significantly better prognosis than those with
      high cyclin E expression and positive BVI. CONCLUSIONS: The expression of cyclin
      E is independent prognostic factor in rectal carcinoma at stages I- III.
      Detecting the expression of cyclin E and/or combined with BVI may help to predict
      clinical outcome and design further individualized intensive adjuvant treatment.

PMID- 18344088
TI  - [Effect and mechanism of ghrelin and its synthetic peptide growth hormone
      releasing peptide 6 on gastric motor in mice].
AB  - OBJECTIVE: To investigate the effect and mechanism of ghrelin and its synthetic
      peptide GHRP-6 on gastric motor in mice. METHODS: In vivo, the dose-dependent
      effects of ghrelin (20,50,100,200 mug/kg) and GHRP-6 (20,50,100,200 mug/kg) on
      gastric emptying were measured by intragastric application of phenol red test
      which was adapted for use in mice. The effects of atropine, NG-nitro-L-arginine
      methyl ester (L-NAME), and D-Lys(3)-GHRP-6 (GHS-R antagonist) on the gastric
      motor induced by ghrelin and GHRP-6 (100 mug/kg) were also investigated. In
      vitro, the effects of ghrelin (0.01,0.1,1.0,10.0 mumol/L) and GHRP-6
      (0.01,0.1,1.0,10.0 mumol/L) on spontaneous contraction of mice fundic muscle
      strips were studied as well. RESULTS: Both ghrelin (50,100,200 mug/kg) and GHRP-6
      (50,100,200 mug/kg) significantly accelerated gastric emptying (P<0.05), but they
      failed to accelerate gastric emptying in the presence of atropine, L-NAME and D
      Lys(3)-GHRP-6 (P<0.05). Ghrelin (0.1, 1.0, 10.0 mumol/L) and GHRP-6 (0.1, 1.0,
      10.0 mumol/L) induced significant contraction of fundic muscle strips in
      concentration-dependent manner (P<0.05), which could be blocked by tetrodotoxin.
      CONCLUSION: Ghrelin and its synthetic peptide GHRP-6 accelerate gastric emptying
      perhaps by activating GHS-R of cholinergic excitatory pathways and nitrergic
      nervous pathways in the enteric nervous system.

PMID- 18344089
TI  - [Protective effect of ethyl pyruvate on barrier function of intestinal mucosa in
      dogs with septic shock].
AB  - OBJECTIVE: To investigate the effect of ethyl pyruvate on barrier function of
      intestinal mucosa in dogs with septic shock. METHODS: Twenty dogs with septic
      shock induced by lipopolysaccharides(LPS) were randomly divided into two groups.
      Dogs randomly received placebo (Ringer's solution, control group, n=8) or ethyl
      pyruvate in lactated Ringer's solution (0.05 g/kg loading dose over 10 mins,
      thereafter 0.05 g.kg(-1).h(-1) for 12 hours, EP treatment group, n=12). The
      diamine oxidase(DAO) activity and D-lactate content were detected at the 0, 8 th,
      12 th and 24 th hour of septic shock. Animals were sacrificed at the 24 th hour
      after septic shock and the jejunal tissue was taken for histopathological
      examination. RESULTS: The levels of plasma DAO and D-lactate were significantly
      elevated in both groups after septic shock than those before septic shock. The
      changes in intestinal parameters of hemoperfusion and permeability in EP
      treatment group were significantly lowered than those in control group.
      Inflammation of small intestinal mucosa was more severe in control group than
      that in EP group, and the pathologic score was significantly lower in EP
      group(2.33+/-0.25) than that in control group(3.39+/-0.38)(P<0.05). CONCLUSION:
      Ethyl pyruvate can lessen intestinal permeability and protect intestinal barrier
      function in dogs with septic shock.

PMID- 18344090
TI  - Unintentional injury mortality trends in children and adolescents in Lithuania
      between 1971 and 2005.
AB  - The objectives of the study were to estimate mortality rate trends due to road
      traffic, drowning and fire/burns in children aged 0-14 years and in adolescents
      aged 15-19 years in Lithuania between the years 1971-2005. The data were obtained
      from Statistics Lithuania and the Health Information Centre. Trends were
      estimated by linear and polynomial regression. The study revealed that the child
      and adolescent unintentional injury mortality rates show declining trends. For
      children, the significant decreasing trends of mortality rates due to road
      traffic, drowning and fire/burns were observed. For adolescents there were
      significant decreasing trends for drowning deaths, and insignificant decreasing
      tendencies for deaths from fire/burns. There was an insignificant increased road
      traffic mortality rate trend for adolescent girls. For the adolescent boys group
      and for boys and girls together from the beginning of the study period there were
      increasing trends, followed by declining trends. In the last years, the increase
      was observed again.

PMID- 18344091
TI  - Estimating road traffic mortality more accurately: use of the capture-recapture
      method in the West Azarbaijan province of Iran.
AB  - The study estimates the rate of fatal road traffic injuries (RTIs) by population
      and road-users group in one Iranian province. The capture - recapture method was
      employed, using both the death register and the forensic medicine register over
      one year. They recorded totals of 669 and 665 RTIs respectively, giving a non
      overlapping number of 897 cases. An estimate of 1018 fatalities occurred, at
      rates of 34 per 100,000 of the population for all road users aggregated, 10 per
      100,000 for pedestrians and 25 per 100,000 for other road users. Coverage was
      somewhat better for victims less than 15 years of age, and also for males. The
      method showed 121 under-reported cases in both sources; however, it can help
      Iranian policy-makers to produce a good estimation of fatal RTIs number each
      year, when following up current RTIs-prevention programmes. Yet, given that each
      registry operates separately, optimum coverage will only be obtained when both
      sources are integrated and work together.

PMID- 18344092
TI  - Productivity losses from road traffic deaths in Turkey.
AB  - The importance of road traffic injuries in Turkey is not generally appreciated,
      in part due to lack of knowledge of its economic burden and in part due to major
      underestimation in official statistics. The total years of potential life lost
      and potentially productive years of life lost from mortality were calculated in
      order to estimate the cost of productivity losses from road traffic deaths in
      Turkey. More years of potentially productive life are lost due to road traffic
      deaths than to respiratory tract illnesses or diabetes mellitus, two other
      serious health problems in Turkey. Road traffic deaths cost Turkey an estimated
      USD 2.6 billion every year in productivity losses alone, more than the World Bank
      estimate of the indirect costs from the 1999 Marmara earthquake (USD 1.2-2
      billion), Turkey's worst earthquake since 1939 (World Bank Turkey Country Office,
      1999). This study highlights the importance of accurate information in
      ameliorating the burden of road traffic safety in Turkey. Turkey has great
      opportunities to implement cost-effective interventions to reduce the economic
      burden of fatal and non-fatal road traffic injuries.

PMID- 18344093
TI  - Mortality in elderly injured patients: the role of comorbidities.
AB  - Home injuries in older people are an important cause of morbidity, disability and
      death. In addition, the presence of a pre-existing disease has generally been
      shown to be associated with higher mortality in this population. The objective of
      the study was to evaluate the association between pre-existing chronic conditions
      and risk of death among older trauma patients. A retrospective study was
      conducted in the Lazio Region, including the city of Rome. The study included all
      the people aged 65 years or older who were admitted to emergency departments in
      the year 2000 for home or road injuries, which was followed by hospitalisation
      within 24 hours. Comorbidities are quantified according to the Charlson
      Comorbidity Index (CCI). The outcome of interest was 30-day mortality. To measure
      the association between comorbidities and the probability of death, logistic
      regression was used, adjusting for triage code, sex, age and place of injury. An
      analysis stratified by triage was also performed. It was found that 17.9% of the
      injured subjects (8145) were affected by one or more chronic conditions. The
      probability of death was higher among males, older people, more severe patients
      and in cases of home accident. Risk of death for non-urgent and urgent patients
      increased with the increasing of the CCI score. Mortality among very urgent
      injured elderly was not affected by the presence of chronic conditions. It was
      concluded that chronic conditions are strong determinants of mortality,
      particularly for mild injuries.

PMID- 18344094
TI  - Accounting for the role of habit in behavioural strategies for injury prevention.
AB  - The limited success of behavioural strategies in injury prevention has been
      attributed to failure to properly apply behaviour change models to intervention
      design and the explanation of safety behaviours. However, this paper contends
      that many health behaviour change interventions do not succeed because they fail
      to take into account the habitual quality of most health and safety-related
      behaviour; a more complete model of behaviour change needs to be based on a
      better understanding of the role of habit. The overall aim is to contribute to
      better understanding of behavioural strategies for injury prevention. When habits
      are weak, attitudes and intentions predict behaviours, but as behaviours turn
      into habits, they become better predictors of future behaviour than attitudes or
      intentions. Furthermore, where habits are strong, individuals are less likely to
      act on new information, evaluating counter-habitual information negatively.
      Integrating the concepts of strong and weak habits with upstream and downstream
      strategies, a framework is presented for tailoring strategies to the habit
      strength of the target behaviour.

PMID- 18344095
TI  - Transferring injury data to decision makers in British Columbia.

PMID- 18344096
TI  - Characteristics of unprotected left-turn accidents at signalised intersections.

PMID- 18344097
TI  - Parental attitudes to supervision and risk of childhood injury: results from a
      primary school cohort.

PMID- 18344098
TI  - Developing a national policy for injury and violence prevention.

PMID- 18344099
TI  - Oral administration of fomepizole produces similar blood levels as identical
      intravenous dose.
AB  - INTRODUCTION: Fomepizole is available intravenously (i.v.) for the treatment of
      methanol and ethylene glycol poisoning. Few studies demonstrate that fomepizole
      achieves effective serum concentrations after i.v. or oral (p.o.) use. The
      objective was to describe the comparative pharmacokinetics of fomepizole after a
      single p.o. and i.v. dose. METHODS: This was a prospective, randomized, crossover
      trial in 10 healthy volunteers. Each received 15 mg/kg fomepizole, p.o. and by 30
      minute i.v. infusion. Serum was collected at 0, 0.25, 0.5, 1, 2, 4, 7, 12, 24,
      36, and 48 hours (h) and stored at -70 degrees C. Candidate models were fit to
      the i.v. and p.o. data, simultaneously, using iterative 2-stage analysis weighted
      by the estimated inverse observation variance. Time above the MEC (T>MEC) was
      determined by numeric integration of the fitted functions using 10 micromoles/L
      as the minimum effective concentration (MEC). RESULTS: Seven females and 3 males
      were enrolled. Sole complaints included headache and dizziness in 3 subjects and
      10/10 reported an unpleasant taste. The final PK model was 2-compartment with 0
      order i.v. and 1(st)-order p.o. input (following a fitted TLag) and Michaelis
      Menten elimination. p.o. fomepizole was rapidly absorbed with a bioavailability
      of approximately 100%. The Km was 0.935+/-0.98 micromoles/L and the Vmax was
      18.57+/-9.58 micromoles/L/h. T>MEC was 32 h with agreement between p.o. and i.v.
      dosing. CONCLUSIONS: This is the first study that effectively determines a human
      Vmax and Km for p.o. and i.v. fomepizole. p.o. and i.v. administration of
      fomepizole result in similar pharmacokinetic parameters.

PMID- 18344100
TI  - High mortality rates among GHB abusers in Western Sweden.
AB  - BACKGROUND: GHB is a drug of abuse and acute poisonings have been an increasing
      medical problem over the last decade in Sweden. OBJECTIVES: To document all cases
      of GHB poisonings in Gothenburg during 1995-2004 and to record drug-related
      deaths to compare the toxicity of GHB with other illicit drugs, such as heroin
      and amphetamine. METHODS: The number of GHB-poisoned patients treated at the
      Sahlgrenska University Hospital has been recorded with the help of an in-house
      database. The number of deaths by illicit drugs was recorded during 2004.
      Seizures of the drugs GHB, 1,4-butanediol, and GBL were registered between 1996
      and 2004. RESULTS: The number of poisoned patients was 259. The number of
      seizures with GHB was 743, GBL 343, and 1,4-butanediol 236. In 2004 the number of
      deaths was 6 with heroin, 7 with GHB, 32 with amphetamine, 6 with cocaine, and
      one with methadone. One patient with GHB poisoning died during hospital care.
      CONCLUSIONS: Intoxication by GHB has substantial morbidity and abuse of GHB has
      substantial mortality. The acute prognosis is good but long-term prognosis is
      insecure with an increased risk for drug dependency and an early death.

PMID- 18344101
TI  - Pest controllers: a high-risk group for Multiple Chemical Sensitivity (MCS)?
AB  - INTRODUCTION: Based on the assumption that professional groups with frequent
      chemical exposure are at an increased risk for developing Multiple Chemical
      Sensitivity (MCS), a sample of 45 professional pest controllers was investigated.
      METHODS: The examination of the pest controllers consisted of a physical and
      laboratory examination with urine screening for pyrethroid metabolites, a
      psychiatric interview, a neuropsychological test battery, and a chemical
      sensitivity questionnaire. RESULTS: Persistent or serious work related health
      problems and chemical sensitivity were not reported. In urine, cis-3-(2,2
      dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (Br(2)CA) was detected
      in 11%, 4-fluoro-3-phenoxybenzoic acid (F-PBA) in 7%. 3-phenoxybenzoic acid (3
      PBA) exceeded the reference range in 9%, cis- and trans-3-(2,2-dichlorovinyl)-2,2
      dimethyl-cyclopropane-1-carboxylic acid (Cl(2)CA) in 20%. Increased liver enzymes
      and blood count deviations were rather common. 38% had psychiatric disorders.
      With few exceptions, neuropsychological testing results were normal. CONCLUSIONS:
      The results do not support the hypothesis that work-related insecticide exposure
      promotes chemical sensitivity.

PMID- 18344102
TI  - Envenomation by the asp caterpillar (Megalopyge opercularis).
AB  - BACKGROUND: The Asp Caterpillar, Megalopyge opercularis, is endemic to the
      southern United States and causes hundreds of human envenomations annually.
      Envenomation from the spines of the caterpillar causes severe pain, burning,
      swelling, nausea, abdominal distress, and headache. Despite the high prevalence
      of envenomations, little is known about the caterpillars, their geographical
      distribution, and the symptoms they engender. METHODS: We collected and analyzed
      188 case reports of asp caterpillar envenomations over a three-year period.
      RESULTS: The geographical distribution of the caterpillars is confined to the
      southeast United States, largely in Texas, Louisiana, and Florida. Symptoms of
      envenomation vary, but typically include burning pain, swelling, nausea, and
      itching. The peak months of envenomation are July through November, with few
      cases reported at other times of year. DISCUSSION: This study sheds light on the
      caterpillars' distribution and the range of symptoms caused in order to aid in
      diagnosing puss moth caterpillar envenomation.

PMID- 18344103
TI  - Comparison of SPECT findings and neuropsychological sequelae in carbon monoxide
      and organophosphate poisoning.
AB  - Abnormal regional cerebral blood flow in patients with acute carbon monoxide (CO)
      and organophosphate (OP) poisoning was examined using (99m)Tc-hexamethylpropylene
      amine oxime (HMPAO) brain single photon emission computed tomography (SPECT) in
      fourteen patients. We evaluated the predictive significance of acute phase brain
      SPECT findings for long-term neuropsychological sequelae. Changes were found in
      the frontal, temporal, parietal lobes within the first week after both types of
      poisoning. The distribution of the hypoperfused cerebral areas as demonstrated by
      (99m)Tc-HMPAO imaging was similar in the two groups during the acute phase.
      Neuropsychological sequelae developed in five patients poisoned with OP and six
      with CO. Patients who had SPECT findings heterogeneously or in the temporal or
      frontal lobes displayed disorientation. Those with fronto-parietal and frontal
      lobe changes displayed mental confusion. Parkinsonism also was observed in
      patients with parieto-occipital, parietal and frontal lobe lesions. The
      distribution of these lesions appears to predict the long term sequelae of these
      poisonings, though additional studies with larger numbers of patients are needed
      to confirm the role of SPECT imaging in both OP and CO poisonings.

PMID- 18344104
TI  - A clinical decision rule for triage of children under 5 years of age with
      hydrocarbon (kerosene) aspiration in developing countries.
AB  - BACKGROUND: Unintended hydrocarbon ingestion is a common reason for pediatric
      hospitalization in the developing world. OBJECTIVE: To derive a clinical decision
      rule, to identify patients likely to require a higher level facility (resource
      requiring cases), that can be used at primary health care facilities with limited
      diagnostic and therapeutic resources. METHODS: A prospective study of children 2
      to 59 months old presenting to a poison treatment facility within 2 hours of oral
      hydrocarbon exposure. History and objective signs were recorded at admission and
      at 6, 12, 24 and, if present, 48 hours. Inclusion in the resource-requiring
      outcome group required: oxygen saturation <94%; any CNS depression; any treatment
      with (salbutamol); any care in the ICU; or death. RESULTS: 256 met the inclusion
      criteria and completed the study. Of these, 170 had a course requiring resources
      unavailable at most primary health care facilities, and 86 did not. The presence
      of wheezing, any alteration in consciousness (lethargy or any restlessness), or a
      rapid respiratory rate for age (RR >or= 50/min if age < 12 mo, >or= 40/min if age
      >or= 12 mo) at presentation identified 167 of 170 of these patients (sensitivity
      0.98). Thirty-six of 86 patients classified as non-resource requiring were
      correctly identified (specificity 0.42). No combination of clinical symptoms
      provided better discrimination while preserving sensitivity. CONCLUSIONS: This
      study suggests a triage decision rule based on the presence of wheezing, altered
      consciousness, or a rapid respiratory rate within 2 hours of hydrocarbon
      exposure. Such a rule requires validation in other settings.

PMID- 18344105
TI  - Kinetics and determinants of the changes of CC16, a lung secretory protein in a
      rat model of toxic lung injury.
AB  - PURPOSE: To investigate the kinetics and the determinants of the changes of the
      Clara cell 16 kDa protein (CC16) as a marker of lung injury following exposure to
      different toxicants. METHODS: Rats were treated with 4-Ipomeanol (IPO), alpha
      naphtylthiourea (ANTU), sodium chromate (Na(2)CrO(4)) or paraquat-(PQ). The
      changes of CC16, total protein, albumin, and cystatin-C were determined on BALF
      supernatan, and CC16, cystatin-C and creatinine levels were also determined in
      serum. RESULTS: Bronchiolar insult due to IPO or ANTU resulted in an initial
      transient increase of serum CC16, parallel to that of albumin in BALF, and a
      subsequent reduction in both BALF and serum. A slight reduction of CC16 in BALF
      was already apparent one hour following treatment with PQ. In the serum, CC16
      increased to 400% of basal value. With PQ and Na(2)CrO(4), the elevation of CC16
      was mainly determined by the degree of renal impairment.

PMID- 18344106
TI  - Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines,
      cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly
      medical patients.
AB  - BACKGROUND: Undisclosed use of illicit drugs and prescription controlled
      substances is frequent in some settings. The aim of the present study was to
      estimate the reliability of self-reported use of amphetamine, barbiturates,
      benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely
      hospitalized medical patients. METHODS: Patients admitted to an acute medical
      department were interviewed about their drug use. Patients provided blood and
      urine samples for drug analysis. Results of a toxicology screen were compared to
      self-reported drug use. Toxicology screens positive for drugs not reported during
      the interview were only considered truly positive after verification by a
      substance specific analysis. RESULTS: Five hundred patients were included. The
      median age was 72 years and 298 (60%) were female. In total, 103 patients (21%)
      reported use of opiates and 65 patients (13%) used benzodiazepines. Only 8
      patients reported use of illicit drugs (cannabinoids, 2%). Toxicology analyses
      were performed in a randomly selected sub-sample of 100 patients. Among 27
      patients (27%), the analyses indicated use of one or more drugs, mainly
      benzodiazepines (15 patients), morphine (12 patients) or cannabinoids (5
      patients). Another 6 patients had screenings unexpectedly positive for opiates,
      but the verification analysis indicated use of codeine-containing drugs. The
      overall sensitivity of self-reports in detecting drug use was 66%. The negative
      predictive value of a patient not reporting use of a drug was over 90% for all 7
      drug-types screened. CONCLUSION: Among 100 randomly selected mainly elderly
      medical patients, undeclared use of illicit drugs was rare. However, some
      patients underreported use of benzodiazepines and cannabinoids.

PMID- 18344107
TI  - Are recommended doses of acetaminophen hepatotoxic for recently abstinent
      alcoholics? A randomized trial.
AB  - Although acetaminophen overdose is a leading cause of fulminant hepatic failure,
      it is controversial whether therapeutic doses of acetaminophen can cause
      hepatotoxicity in alcoholics, especially those rendered most vulnerable by recent
      abstinence. We performed a randomized, triple-blind, parallel-group trial
      comparing sustained-release acetaminophen, 1300 mg orally q8h for 11 doses,
      against placebo. We enrolled chronic alcohol abusers (defined as >or= 6 drinks
      daily for >or= 6 weeks) who had discontinued alcohol consumption 12 to 72 hours
      prior to enrollment. Individuals with self-reported viral hepatitis, HIV or
      intravenous drug use, baseline AST or ALT >120 IU/L, or INR >1.5 were excluded.
      Hepatic function tests were drawn daily for 5 days. The primary outcome was
      change in serum alpha-GST, a sensitive experimental biomarker of hepatocellular
      injury; secondary outcomes were changes in serum AST, ALT, INR, and study
      withdrawal for a doubling of aminotransferases to >120 IU/L. Of 52 subjects
      randomized, 40 completed at least four days of intervention. Subjects receiving
      acetaminophen had 32% [95% CI 7%, 50%] and 29% [6%, 46%] lower serum alpha-GST
      concentrations on days 2 and 3, respectively, compared to placebo, but these
      differences disappeared by day 4. No subjects were withdrawn for safety reasons.
      In conclusion, therapeutic doses of sustained-release acetaminophen cause a
      measurable decrease in serum alpha-GST during the first days of abstinence from
      chronic alcohol use. While the mechanism is unclear, these observations do
      provide some reassurance that short courses of acetaminophen are unlikely to
      cause subclinical hepatocellular injury in recently abstinent alcoholics.

PMID- 18344108
TI  - Severe uvular edema and nasal mucosal necrosis due to Ecbalium elaterium
      (squirting cucumber): an allergic reaction or direct toxic effect?
AB  - Ecbalium elaterium or squirting cucumber is a plant growing in the Mediterranean
      region, belong to Cucurbitaceae family. Its juice has been used as an herbal
      medicine since ancient times because of its cathartic and anti-inflammatory
      effects. It has been reported to cause upper airway edema, especially after the
      administration of its undiluted form. It has generally been attributed to
      allergic reaction. In this case report we aimed to interrogate this anticipation
      by presenting a case of severe uvular edema and nasal mucosal necrosis after
      dripping undiluted Ecbalium elaterium juice that did not improved by anti
      allergic therapies.

PMID- 18344109
TI  - Cerebellar effects after consumption of edible morels (Morchella conica,
      Morchella esculenta).
AB  - Morchella esculenta and Morchella conica are well known edible morels, which
      seldom induce clinical symptoms. We report six persons who developed cerebellar
      effects 6-12 hours after consumption of these mushrooms. The symptoms were self
      limited and disappeared after one day.

PMID- 18344110
TI  - Withdrawal from high-dose tranylcypromine.
AB  - A 34-year-old man with a history of multiple substance abuse (now abstinent for
      six years) became addicted to tranylcypromine, consuming up to 240 mg/day. After
      discontinuing the drug, he developed thrombocytopenia (52,000/ul) and delirium;
      there were no other anticholinergic signs. The delirium was unresponsive to
      haloperidol and diazepam. Intravenous administration of physostigmine (2 mg) on
      hospital day 6 resulted in prompt, but temporary, clearing of the delirium.
      Following a recurrence of the delirium after 30 minutes, he was started on an
      intravenous infusion of physostigmine (2 mg/hr) with good results. Physostigmine
      administration did not produce any cholinergic signs. By hospital day 8, he did
      not require any more physostigmine. Thrombocytopenia resolved on hospital day 9
      without therapeutic intervention. On hospital day 10, the patient was
      asymptomatic and left the hospital on his own recognizance.

PMID- 18344111
TI  - A case of 5-fluorouracil-induced peripheral neuropathy.
AB  - The standard adjuvant therapy for rectal cancer is 5-fluorouracil (5-FU) often
      combined with radiotherapy. Well-documented side effects of 5-FU include nausea,
      vomiting and diarrhoea, leukopenia and thrombocytopenia, hand-foot syndrome,
      mucositis, and cardiotoxicity. Peripheral neurotoxicity has only rarely been
      reported. We report a patient with a stage II rectal carcinoma who developed a
      mild axonal sensorimotor neuropathy at the end of a 5-FU therapy.

PMID- 18344112
TI  - Acute overdose with controlled-release levodopa-carbidopa.
AB  - INTRODUCTION: Reports of acute levodopa-carbidopa overdose are rare and no case
      of an acute overdose with a controlled-release formulation has been described. We
      describe such a case in which serial concentrations of catecholamines were
      measured. CASE REPORT: A 55-year-old man ingested 89 tablets of Sinemet 50/200
      (17.8 g of levodopa, 4.45 g of carbidopa). Clinical effects and plasma
      concentrations of dopamine, noradrenaline and adrenalin were assessed over 66
      hours. On admission 2.5 hours after the ingestion, his physical examination was
      normal except for mydriasis and urine retention. Five hours post-ingestion he had
      psychomotor agitation, delirium with logorrhea, joviality, visual hallucinations,
      regular sinus tachycardia and xerostomia. The clinical course included two
      episodes hypotension and four of transient tachycardia. Treatment was symptomatic
      and supportive. Clinical toxicity reappeared 48 hours after the intoxication. The
      patient was discharged at the end of the fourth day with amnesia for the event.
      DISCUSSION: Dopamine showed an initial plasma concentration peak 14 hours after
      the toxic ingestion, followed by a second peak 38 hours after the ingestion. The
      initial peak of noradrenaline occurred 20 hours post-ingestion with a second
      lower peak at 38 hours. There were no elevations in adrenalin concentrations.
      CONCLUSION: There appeared to be no correlation between the intensity of the
      clinical signs and the blood concentrations of dopamine and noradrenaline,
      although the resolution of the clinical signs did correspond to these
      catecholamines return to normal values. Patients who ingest controlled-release
      formulations need to be observed until after the second catecholamine peak.

PMID- 18344113
TI  - Occurrence of singlet oxygen oxygenation of oleic acid and linoleic acid in the
      skin of live mice.
AB  - To assess the contribution of singlet molecular oxygen [O(2) ((1)Delta(g))] to
      lipid peroxidation in vivo, this study combined gas chromatography-mass
      spectrometry with thin layer chromatography to analyse peroxidized lipids in the
      skin of hairless mice. Hydroxyoctadecenoate isomers and unconjugated
      hydroxyoctadecadienoate isomers derived from peroxidized oleic acid and linoleic
      acid, respectively, which are specific to O(2) ((1)Delta(g))-dependent
      oxygenation, were detected in the skin of live mice under ordinary feeding
      conditions. Short-term ultraviolet A (UVA)-irradiation of the skin in vivo
      elevated levels of the unconjugated hydroxyoctadecadienoate isomers
      significantly, whereas the irradiation of skin homogenate in vitro increased
      levels of all isomers derived from both O(2) ((1)Delta(g)) and free radical
      dependent oxygenation to a much greater extent. This is the first report to
      demonstrate the occurrence of O(2) ((1)Delta(g))-specific oxygenation of
      unsaturated fatty acids in living animals.

PMID- 18344114
TI  - The distribution of 4-hydroxynonenal-modified proteins in gastric mucosa of
      duodenal peptic ulcer patients.
AB  - This study used monoclonal antibody specific for 4-hydroxynonenal (HNE)-histidine
      to evaluate immunohistochemical distribution of HNE-protein adducts in gastric
      mucosa biopsies of 52 peptic ulcer patients (all positive for H. pylori) and of
      20 healthy volunteers (eight positive and 12 negative for H. pylori). HNE
      modified proteins were present in glandular epithelium in all subjects, both
      patients with duodenal peptic ulcer and healthy subjects. Hence, the presence of
      HNE did not appear to be related to the presence of H. pylori. However, in
      patients with duodenal peptic ulcer accumulation of HNE-protein adducts was
      frequently observed also in nuclei, while in the control group such subcellular
      distribution of HNE was not observed at all. This study shows physiological
      presence of HNE in human gastric mucosa, but also suggests its role in pathology
      of gastric dysfunction in duodenal peptic ulcer patients manifested by
      accumulation of HNE-protein adducts in particular in nuclei of gastric glandular
      epithelium.

PMID- 18344115
TI  - Calcium ionophore-induced egg activation and apoptosis are associated with the
      generation of intracellular hydrogen peroxide.
AB  - The present study was designed to investigate whether calcium ionophore-induced
      activation and apoptosis are associated with the generation of hydrogen peroxide
      (H(2)O(2)) in rat eggs cultured in vitro. Culture of metaphase-II (M-II) arrested
      eggs in Ca(2+)/Mg(2+)-deficient medium did not induce egg activation, while a
      second polar body was observed in 20% of eggs when cultured in Ca(2+)/Mg(2+)
      supplemented medium. In Ca(2+)/Mg(2+)-deficient medium, lower concentrations of
      calcium ionophore (0.2,0.4 and 0.8 microm) not only induced egg activation in a
      dose-dependent manner but also generation of intracellular H(2)O(2) (84.40+/-0.50
      ng/egg) when compared to control eggs (80.46+/-1.34 ng/egg). The higher
      concentration of calcium ionophore (1.6 microm) induced apoptosis and pronounced
      generation of intracellular H(2)O(2) (92.43+/-0.93 ng/egg) in treated eggs.
      Conversely, cell-permeant antioxidant such as 2(3)-tert-butyl-4-hydroxyanisole
      (BHA) reduced intracellular H(2)O(2) level (81.20+/-1.42 ng/egg) and protected
      against calcium ionophore-induced morphological changes characteristics of egg
      activation and apoptosis. These results clearly suggest that calcium ionophore
      induced activation and apoptosis are associated with the generation of
      intracellular H(2)O(2) in rat eggs.

PMID- 18344116
TI  - Increased mitochondrial oxidative damage and oxidative DNA damage contributes to
      the neurodegenerative process in sporadic amyotrophic lateral sclerosis.
AB  - To investigate the possibility that mitochondrial oxidative damage or oxidative
      DNA damage or both contribute to the neurodegenerative process of sporadic
      amyotrophic lateral sclerosis (sALS), this study used high-performance liquid
      chromatography with an electrochemical detector to measure the concentrations of
      the reduced and oxidized forms of coenzyme Q10 (CoQ10) and 8-hydroxy-2'
      deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 17 patients with sALS
      and 17 age-matched controls with no neurological diseases. The percentage of
      oxidized CoQ10 in the CSF of sALS patients was greater than that in the CSF of
      controls (p<0.002) and was negatively correlated with the duration of illness
      (rho=-0.61, p<0.01). The concentration of 8-OHdG in the CSF of sALS patients was
      greater than that in the CSF of controls (p<0.005) and was positively correlated
      with the duration of illness (rho=0.53, p<0.005). The percentage of oxidized
      CoQ10 was correlated with the concentrations of 8-OHdG in the CSF of sALS
      patients (rho=-0.53, p<0.05). These results suggest that both mitochondrial
      oxidative damage and oxidative DNA damage play important roles in the
      pathogenesis of sporadic amyotrophic lateral sclerosis.

PMID- 18344117
TI  - Anti-hypertensive effects of Rosuvastatin are associated with decreased
      inflammation and oxidative stress markers in hypertensive rats.
AB  - Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory
      properties. The aim of this study was to evaluate in normotensive (WKY) and in
      spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment
      on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA)
      levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and
      (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines
      were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in
      WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In
      the experimental conditions, ROSU did not modify plasma cholesterol levels in SHR
      but attenuated the increase in systolic blood pressure. In SHR only, ROSU
      lessened pro-inflammatory cytokines and ADMA levels, increased IL-4 and reduced
      ROS production in circulating monocytes. These results demonstrate the beneficial
      effects of ROSU in SHR, independently of any lowering of cholesterol levels.

PMID- 18344118
TI  - Distinct H2O2 concentration promotes proliferation of tumour cells after
      transient oxygen/glucose deprivation.
AB  - A solid tumour undergoes ischemia/reperfusion due to deficient vascularization
      and subsequent formation of new blood vessels. This study investigated the effect
      of transient oxygen and glucose deprivation (OGD) on proliferation of C6 glioma
      cells. The cells were subjected to 18 h of OGD followed by reoxygenation in the
      presence of glucose and different extra-cellular H(2)O(2) concentrations since
      H(2)O(2) affects cell proliferation. After reoxygenation, the cellular H(2)O(2)
      concentration was increased returning to control levels within 24 h. Within this
      period, increase in cell number and MTT-reduction were impaired. Regeneration was
      completed on the third day of reoxygenation. MTT-reduction increased faster than
      cell number, indicating an OGD-dependent up-regulation of protein expression. It
      is concluded that ischemia/reperfusion stress promotes proliferation of tumour
      cells. An essential factor is a distinct H(2)O(2) concentration. Massive
      elevation as well as significant reduction of H(2)O(2) concentration impairs the
      proliferation process.

PMID- 18344119
TI  - Scavenging of free radicals in gas-phase mainstream cigarette smoke by
      immobilized catalase at filter level.
AB  - Catalase is well known as capable of inducing the decomposition of H(2)O(2). In
      this study, a kind of immobilized catalase (entrapped in cross-linked chitosan
      beads) was dispersed in conventional acetate filter as an antioxidant additive.
      Quantitative estimation of the free radicals in mainstream cigarette smoke (MCS)
      was performed to address the effect of this modified filter. It was found that
      the levels of PBN adduct and NO(*)/NO(2)(*) associated with the gas-phase
      mainstream cigarette smoke (GPCS) were efficiently decreased by approximately 40%
      through catalase filtering. Besides, the modified filter was found to lower the
      MCS-induced adverse biological effects including lipid peroxidation and
      mutagenicity. This was proved to be substantially attributed to the catalase
      dependent breakdown of NO(*), which was stimulated by some of peroxides (most
      probably being H(2)O(2)), the dismutation products of tar particulate matters
      (TPM). These results highlighted a promising approach to reduce the smoking
      associated health risks to passive smokers. Moreover, the mechanisms of catalase
      filtering may be helpful for the development of appropriate immobilized enzyme
      systems to be applied for reducing health risks associated with gaseous
      pollutants.

PMID- 18344120
TI  - Flow cytometric estimation of 'labile iron pool' in human white blood cells
      reveals a positive association with ageing.
AB  - A small part of cellular iron, usually called 'labile iron pool' (LIP), is not
      securely stored and has the potential to catalyse the formation of highly
      reactive oxygen species. The present work estimated LIP levels in human white
      cells by using the analytical power of flow cytometry. The method relies
      essentially on already established principles but has the added value of
      monitoring LIP in different subpopulations of human blood cells concurrently in a
      single sample. Examination of 41 apparently healthy individuals revealed a
      positive correlation between LIP levels and the age of the donors (r=0.656, 0.572
      and 0.702 for granulocytes, lymphocytes and monocytes, respectively, p<0.0001),
      indicating that cells of older individuals are prone to oxidations in conditions
      of oxidative stress. It is suggested that LIP estimation may represent a valuable
      tool in examinations searching for links between iron and a variety of oxidative
      stress-related pathological conditions.

PMID- 18344121
TI  - Supplementation of alpha-tocopherol improves cardiovascular risk factors via the
      insulin signalling pathway and reduction of mitochondrial reactive oxygen species
      in type II diabetic rats.
AB  - This study determined the effects of alpha- and gamma-tocopherol supplementation
      on metabolic control and oxidative stress in type 2 diabetic Otsuka Long-Evans
      Tokushima Fatty (OLETF) rats. Blood glucose, haemoglobin A1c (HbA1c), urinary
      protein, plasma free fatty acid, triacylglycerol and plasminogen activator
      inhibitor-1 (PAI-1) levels in OLETF rats were significantly higher than in non
      diabetic control Long-Evans Tokushima Otsuka (LETO) rats. Alpha-tocopherol
      inhibited the increase in urinary protein, blood glucose, HbA1c and PAI-1 levels,
      but gamma-tocopherol did not. Plasma and hepatic lipid peroxidation and hepatic
      steatosis were increased in OLETF rats. alpha-Tocopherol decreased lipid
      peroxidation. Mitochondrial reactive oxygen species production and uncoupling
      protein 2 (UCP2) expression were significantly increased in the heart and aorta
      of OLETF rats compared with LETO rats. Endothelial NO synthase and aortic
      nitrotyrosine were increased in OLETF rats. In contrast, the expression of
      phosphorylated vasodilator-stimulated phosphoprotein and glucose transporter 4 in
      the aorta was significantly decreased in OLETF rats. These abnormalities were
      reversed by alpha-tocopherol. These findings suggest that alpha-tocopherol may
      prevent cardiovascular tissues from oxidative stress and insulin signalling
      disorder resulting from diabetes mellitus.

PMID- 18344122
TI  - Vitamin E ingestion improves several immune functions in elderly men and women.
AB  - The effects of diet supplementation with the antioxidant vitamin E (200 mg daily)
      on several blood neutrophil, lymphocyte and natural killer cell functions have
      been investigated in healthy elderly men and women before supplementation, after
      3 months of supplementation and 6 months after the end of supplementation (post
      supplementation). In parallel, samples of healthy adult men and women were used
      as age controls. In elderly men and women, an impairment of immune functions was
      observed in comparison with the respective adult controls and the intake of
      vitamin E resulted in a significant enhancement of immune parameters in both
      elderly men and women, bringing their values close to those in the adults. These
      effects were not found in post-supplementation samples in several but not in all
      functions. The present findings suggest that supplementation with vitamin E can
      produce an improvement of immune functions and therefore of health in aged
      people.

PMID- 18344123
TI  - Effect of polar solvents on beta-carotene radical precursor.
AB  - Beta-carotene forms radicals in chloroform upon photo-excitation (i) in the
      femtosecond time-scale by direct electron ejection into chloroform and (ii) in
      the microsecond time-scale by secondary reactions with chloroform radicals formed
      in the faster reactions. The precursor for beta-carotene radical cation decays in
      a second-order reaction in the mixed solvents, with a rate decreasing for
      increasing dielectric constant of cosolvent (acetic acid < ethanol < acetonitrile
      approximately methanol). The precursor is assigned as an ion pair from which the
      beta-carotene radical cation is formed in neat chloroform, but in more polar
      solvents it reacts at least partly through disproportionation in a bimolecular
      reaction promoted by the presence of ions. The stabilization of the radical
      precursor by increased solvent polarity, allowing for deactivation of the
      precursor by an alternative reaction channel, is discussed in relation to the
      balance of pro- and antioxidative properties of beta-carotene at lipid/water
      interfaces.

PMID- 18344125
TI  - An investigation of a novel three-dimensional activity monitor to predict free
      living energy expenditure.
AB  - The aim of this study was to assess the capability of the 3dNX accelerometer to
      predict energy expenditure in two separate, free-living cohorts. Twenty-three
      adolescents and 14 young adults took a single dose of doubly labelled water and
      wore a 3dNX activity monitor during waking hours for a 10-day period while
      carrying out their normal routines. Multiple linear regression with backward
      elimination was used to establish the strength of the associations between
      various indices of energy expenditure, physical activity counts, and
      anthropometric variables. 3dNX output accounted for 27% and 35% of the variance
      in the total energy expenditure of the adolescent and young adult cohort,
      respectively. The explained variance increased to 78%, with a standard error of
      estimate of 7%, when 3dNX output was combined with body composition variables.
      The 3dNX accelerometer can be used to predict free-living daily energy
      expenditure with a standard error of estimate of 1.65 MJ in adolescents and 1.52
      MJ in young adults. The inclusion of anthropometric variables reduces the error
      to approximately 1 MJ. Although it remains to cross-validate these models in
      other populations, early indications suggest that the 3dNX provides a useful
      method of predicting energy expenditure in free-living individuals.

PMID- 18344126
TI  - On referee bias, crowd size, and home advantage in the English soccer
      Premiership.
AB  - In a recent paper in this journal, Boyko and colleagues (2007) identified
      differences in attendance and referee bias as factors influencing home advantage
      at soccer matches in the English Premiership. A replication of their study using
      more recent data found no evidence to sustain either of their claims.

PMID- 18344127
TI  - Soccer penalty takers' uniform colour and pre-penalty kick gaze affect the
      impressions formed of them by opposing goalkeepers.
AB  - In this study, we examined the impact of soccer players' uniform colour and gaze
      behaviour on the impressions that are formed of them by opposing goalkeepers.
      Twelve soccer goalkeepers observed video footage, filmed from between the
      goalposts to simulate their usual viewpoint, of four players preparing to take a
      penalty kick. Each of the four players displayed a different combination of gaze
      (either 90% or 10% with gaze operationalized as looking directly at the camera)
      and uniform colour (red or white). Goalkeepers rated each player on a series of
      descriptors (e.g. confidence, composure, assertiveness) and rated their
      expectancies for successfully saving penalty kicks from that player. Analysis
      revealed that those penalty takers displaying 90% gaze were perceived to possess
      positive characteristics to a greater extent than penalty takers displaying 10%
      gaze. Results also revealed penalty takers wearing red were perceived to possess
      positive characteristics to a greater extent than those wearing white.
      Goalkeepers reported higher expectancies of saving penalties from penalty takers
      displaying 10% gaze and wearing white uniforms than any of the other
      combinations. Our results therefore support the potential importance of gaze and
      uniform colour in the formation of impressions and expectancies in sport.

PMID- 18344128
TI  - Red shirt colour is associated with long-term team success in English football.
AB  - The colour of sportswear has been shown to influence the outcome of bouts for
      several different combat sports. The generality of these effects, and whether
      they extend to collaborative forms of contests (team sports), is uncertain. Since
      1947, English football teams wearing red shirts have been champions more often
      than expected on the basis of the proportion of clubs playing in red. To
      investigate whether this indicates an enhancement of long-term performance in red
      wearing teams, we analysed the relative league positions of teams wearing
      different hues. Across all league divisions, red teams had the best home record,
      with significant differences in both percentage of maximum points achieved and
      mean position in the home league table. The effects were not due simply to a
      difference between teams playing in a colour and those playing in a predominantly
      white uniform, as the latter performed better than teams in yellow hues. No
      significant differences were found for performance in matches away from home,
      when teams commonly do not wear their "home" colours. A matched-pairs analysis of
      red and non-red wearing teams in eight English cities shows significantly better
      performance of red teams over a 55-year period. These effects on long-term
      success have consequences for colour selection in team sports, confirm that
      wearing red enhances performance in a variety of competitive contexts, and
      provide further impetus for studies of the mechanisms underlying these effects.

PMID- 18344129
TI  - The influence of serial feeding of drinks at different temperatures on
      thermoregulatory responses during cycling.
AB  - In this study, we examined thermoregulatory responses to ingestion of separate
      aliquots of drinks at different temperatures during low-intensity exercise in
      conditions of moderate heat stress. Eight men cycled at 50% (s = 3) of their peak
      oxygen uptake (VO2peak) for 90 min (dry bulb temperature: 25.3 degrees C, s =
      0.5; relative humidity: 60%, s = 5). Four 400-ml aliquots of flavoured water at
      10 degrees C (cold), 37 degrees C (warm) or 50 degrees C (hot) were ingested
      after 30, 45, 60, and 75 min of exercise. Immediately after the 90 min of
      exercise, participants cycled at 95% VO2peak to exhaustion to assess exercise
      capacity. There were no differences between trials in rectal temperature at the
      end of the 90 min of exercise (cold: 38.11 degrees C, s = 0.30; warm: 38.10
      degrees C, s = 0.33; hot: 38.21 degrees C, s = 0.30; P = 0.765). Mean skin
      temperature between 30 and 90 min tended to be influenced by drink temperature
      (cold: 34.49 degrees C, s = 0.64; warm: 34.53 degrees C, s = 0.69; hot: 34.71
      degrees C, s = 0.48; P = 0.091). Mean heart rate from 30 to 90 min was higher in
      the hot trial (129 beats . min(-1), s = 7; P < 0.05) than on the cold (124 beats
      . min(-1), s = 9) and warm trials (126 beats . min(-1), s = 8). Ratings of
      thermal sensation were higher on the hot trial than on the cold trial at 35 and
      50 min (P < 0.05). Exercise capacity was similar between trials (P = 0.963). The
      heat load and debt induced by periodic drinking resulted in similar body
      temperatures during low-intensity exercise in conditions of moderate heat stress
      due to appropriate thermoregulatory reflexes.

PMID- 18344130
TI  - Comparison of different theoretical models estimating peak power output and
      maximal oxygen uptake in trained and elite triathletes and endurance cyclists in
      the velodrome.
AB  - The aim of this study was to assess which of the equations that estimate peak
      power output and maximal oxygen uptake (VO2max) in the velodrome adapt best to
      the measurements made by reference systems. Thirty-four endurance cyclists and
      triathletes performed one incremental test in the laboratory and two tests in the
      velodrome. Maximal oxygen uptake and peak power output were measured with an
      indirect calorimetry system in the laboratory and with the SRM training system in
      the velodrome. The peak power output and VO2max of the field test were estimated
      by means of different equations. The agreement between the estimated and the
      reference values was assessed with the Bland-Altman method. The equation of Olds
      et al. (1995) showed the best agreement with respect to the peak power output
      reference values, and that of McCole et al. (1990) was the only equation to show
      good agreement with respect to the VO2max reference values. The VO2max values
      showed a higher coefficient of determination with respect to maximal aerobic
      speed when they were expressed in relative terms. In conclusion, the equations of
      Olds et al. (1995) and McCole et al. (1990) were best at estimating peak power
      output and VO2max in the velodrome, respectively.

PMID- 18344131
TI  - Relationship between decision-making self-efficacy, task self-efficacy, and the
      performance of a sport skill.
AB  - The purpose of this study was to examine the relationships between decision
      making self-efficacy and task self-efficacy and subsequent decision-making and
      task performance. Sixty undergraduate students (30 males, 30 females)
      participated in this study, which involved infield defensive plays in softball.
      The physical task required participants to throw a ball at a target. The decision
      making task required participants to watch video scenes depicting different
      infield defensive situations and decide where to throw the ball in each
      situation. Both tasks used manipulated failure. Self-efficacy was assessed before
      performance. Strength of decision-making and task self-efficacy predicted
      physical performance, but not decision-making performance.

PMID- 18344132
TI  - The effect of caffeine ingestion on human neutrophil oxidative burst responses
      following time-trial cycling.
AB  - Following fixed-duration exercise of submaximal intensity, caffeine ingestion is
      associated with an attenuation of the exercise-induced decline in N-formyl
      methionyl-phenyl-alanine (f-MLP) stimulated neutrophil oxidative burst. However,
      the response following high-intensity exhaustive exercise is unknown. Nine
      endurance-trained male cyclists ingested 6 mg caffeine or placebo per kilogram of
      body mass 60 min before cycling for 90 min at 70% of maximal oxygen consumption
      (VO2max) and then performing a time-trial requiring an energy expenditure
      equivalent to 30 min cycling at 70% maximum power output. Time-trial performance
      was 4% faster in the caffeine than in the placebo trial (P = 0.043). Caffeine was
      associated with an increased plasma adrenaline concentration after 90 min of
      exercise (P = 0.046) and immediately after the time-trial (P = 0.02). Caffeine
      was also associated with an increased serum caffeine concentration (P < 0.01)
      after 90 min of exercise and immediately after the time-trial, as well as 1 h
      after the time-trial. However, the f-MLP-stimulated neutrophil oxidative burst
      response fell after exercise in both trials (P = 0.002). There was no effect of
      caffeine on circulating leukocyte or neutrophil counts, but the lymphocyte count
      was significantly lower on caffeine (20%) after the time-trial (P = 0.003). Our
      results suggest that high-intensity exhaustive exercise negates the attenuation
      of the exercise-induced decrease in neutrophil oxidative burst responses
      previously observed when caffeine is ingested before exercise of fixed duration
      and intensity. This may be associated with the greater increase in adrenaline
      concentration observed in the present study.

PMID- 18344133
TI  - Open feedback in gymnastic judging causes conformity bias based on informational
      influencing.
AB  - The aims of this study were twofold: (1) to determine whether open feedback (i.e.
      the ability to hear or see the scores of colleague judges after each performance)
      would lead judges in gymnastics to conform with their colleagues, and (2) to
      identify the underlying process on which this conformity is based. Twenty-three
      certified Flemish judges in women's gymnastics were randomly divided into panels
      of a maximum of five judges. These panels had to rate the same 30 videotaped
      individual vaults: 15 in phase 1 and 15 in phase 2. Two independent variables
      were orthogonally manipulated: feedback (or no feedback) during phase 1 and
      feedback (or no feedback) during phase 2. The results of phase 1 revealed that
      the variation between the judges' scores was less within panels that had received
      feedback than within panels that had not received feedback. We therefore conclude
      that the availability of feedback elicits conformity among gymnastic judges. The
      results of phase 2 indicated that this conformity continued even when feedback
      was no longer provided, suggesting that the observed conformity was based on
      informational influencing (i.e. because of uncertainty about the correct
      responses) and not on normative influencing (i.e. out of fear of standing out in
      the group).

PMID- 18344134
TI  - How does practise of internal Chinese martial arts influence postural reaction
      control?
AB  - The aim of this study was to determine the effects of Chinese martial arts
      practice on postural reaction control after perturbation. Participants standing
      in Romberg tandem posture were subjected to an unexpected lateral platform
      translation with the eyes open or closed at two translation amplitudes. The peak
      displacement of the centre of pressure and of the centre of mass, and the onset
      latency of muscular activity (tibialis anterior, gastrocnemius, lumbodorsal
      muscular group, and rectus abdominis), were evaluated for martial arts
      practitioners and for sport and non-sport participants. Compared with the sport
      and non-sport participants, the martial arts group showed lower maximal centre of
      pressure and centre of mass peak displacements in both the lateral and anterior -
      posterior directions, but no difference was found in the onset of muscular
      responses. We conclude that martial arts practice influences postural reaction
      control during a fixed-support strategy in a tandem task. The martial arts group
      used the ankle joint more frequently than the sport and non-sport participants,
      especially in the eyes-closed conditions. Our results suggest that the better
      balance recovery in the martial arts group is a consequence of better control of
      biomechanical properties of the lower limbs (e.g. through muscular response by co
      contraction), not a change in the neuromuscular temporal pattern.

PMID- 18344135
TI  - A model study of optimal training reduction during pre-event taper in elite
      swimmers.
AB  - The aim of this study was to assess responses to taper in elite athletes using
      computer simulations. Parameters of a non-linear model were derived from training
      and performance data over two seasons for eight elite swimmers. The fit between
      modelled and actual performances was statistically significant for each swimmer
      (r(2) = 0.56 +/- 0.06; P < 0.01). The simulations were used to estimate
      characteristics of step and progressive tapers that would maximize performance
      either (1) after regular training only or (2) after overload training of a 20%
      step increase in regular training for 28 days. The highest performance with a
      step taper was greater with than without prior overload training (101.4%, s = 1.6
      vs. 101.1%, s = 1.4 of personal record; P < 0.01) but required a longer taper
      duration (22.4 days, s = 13.4 vs. 16.4 days, s = 10.3; P < 0.05). The optimal
      progressive taper led to a better performance only after the overload period
      (101.5%, s = 1.5; P < 0.001). Negative and positive influences of training were
      estimated as indicators of fatigue and adaptations to training respectively.
      During the optimal taper, the negative influence was completely removed,
      independently of the prior training, whereas the positive influence increased
      only after overload training. Our computer simulations show that the
      characteristics of an optimal training reduction in elite athletes depend on the
      training performed in the weeks prior to a taper.

PMID- 18344136
TI  - Effects of exercise intensity on salivary antimicrobial proteins and markers of
      stress in active men.
AB  - In the present study, we assessed the effects of exercise intensity on salivary
      immunoglobulin A (s-IgA) and salivary lysozyme (s-Lys) and examined how these
      responses were associated with salivary markers of adrenal activation. Using a
      randomized design, 10 healthy active men participated in three experimental
      cycling trials: 50% maximal oxygen uptake (VO2max), 75%VO2max, and an incremental
      test to exhaustion. The durations of the trials were the same as for a
      preliminary incremental test to exhaustion (22.3 min, sx = 0.8). Timed,
      unstimulated saliva samples were collected before exercise, immediately after
      exercise, and 1 h after exercise. In the incremental exhaustion trial, the
      secretion rates of both s-IgA and s-Lys were increased. An increase in s-Lys
      secretion rate was also observed at 75%VO2max. No significant changes in saliva
      flow rate were observed in any trial. Cycling at 75%VOmax and to exhaustion
      increased the secretion of alpha-amylase and chromogranin A immediately after
      exercise; higher cortisol values at 75%VO2max and in the incremental exhaustion
      trial compared with 50%VO2max were observed 1 h immediately after exercise only.
      These findings suggest that short-duration, high-intensity exercise increases the
      secretion rate of s-IgA and s-Lys despite no change in the saliva flow rate.
      These effects appear to be associated with changes in sympathetic activity and
      not the hypothalamic - pituitary - adrenal axis.

PMID- 18344137
TI  - A comparison of methods to determine maximal accumulated oxygen deficit in
      running.
AB  - The aim of this study was to compare maximal accumulated oxygen deficit
      (hereafter O2 deficit) estimated from the methods of Whipp et al. (1986), Medbo
      et al. (1988), and Hill et al. (1998) to determine whether they agree
      sufficiently to be used interchangeably. Nineteen moderately to highly trained
      endurance runners first performed an incremental test to exhaustion for the
      determination of maximal oxygen uptake ([Vdot]O(2max)) and peak treadmill speed,
      followed by six randomly ordered constant-speed tests at 95, 100, 105, 110, 110,
      and 120% of peak treadmill speed. All tests were separated by at least 72 h and
      were performed within 4 weeks. The method of Whipp produced an O(2) deficit
      estimate that was lower than that derived from the method of Hill or Medbo (bias
      +/- 95% limits of agreement: -29.6 +/- 36.6 and -26.1 +/- 32.8 ml . kg(-1),
      respectively; P < 0.001). The O2 deficit did not differ between the methods of
      Hill and Medbo (bias +/- 95% limits of agreement: 3.5 +/- 41.6 ml . kg(-1);
      n.s.). However, poor correlations (0.21 < r < 0.33; n.s.) together with wide
      limits of agreement between O2 deficit estimates (70 - 80% of the mean response)
      clearly question using these methods interchangeably.

PMID- 18344139
TI  - Editorial.

PMID- 18344140
TI  - The contribution of supraglottic laryngeal adjustments to voice: phonetic
      evidence from Arabic.
AB  - In this study, we provide nasendoscopic observations illustrating phonetic
      contrasts in Arabic that require supraglottic laryngeal adjustments, and
      demonstrate how the laryngeal constrictor mechanism contributes to phonetic
      descriptions of phonation. Arabic has two pharyngeal consonants (voiceless and
      voiced). We show, among others, that these two consonants possess auditory
      features of whisperiness and creaky voice, respectively, and are always produced
      with supraglottic constriction similar but more marked than during whispery or
      creaky [i]. However, during modal [i], the epilaryngeal space is wide open. We
      outline a revised model of laryngeal constriction where 'voice' is controlled to
      a large degree by supraglottic as well as glottic mechanisms. Some hypotheses are
      also proposed concerning the possible muscular synergies that induce these
      supraglottic gestures.

PMID- 18344141
TI  - Electroglottographic analysis of valved speech following total laryngectomy.
AB  - Twenty-seven total laryngectomy patients (19 males and 8 females) and 18 normal
      control subjects (10 males and 8 females) were subjected to electroglottography
      based single voice recordings using sustained vowels and connected speech. The
      results showed poorer values and larger variability for all the voice measures
      for the total laryngectomy patients (TO speech) as compared to that of normal
      subjects. There were statistically significant differences (p<0.05) for all study
      parameters between the TO and normal speech. This study shows that robust and
      reliable data can be obtained using electroglottography in laryngectomees with
      both a sustained vowel and connected speech. Using these parameters, TO speech is
      significantly different from normal speech and is highly variable. This
      methodology has enormous potential for further investigations in laryngectomees
      and other patients with head and neck cancer.

PMID- 18344142
TI  - The difficult airway: the use of subglottic jet ventilation for laryngeal
      surgery.
AB  - High-frequency subglottic jet ventilation was used in 352 cases of adults treated
      with suspension microlaryngoscopy. Of these, 89 had difficult airways, and these
      are the subject of this manuscript. All cases were managed by the senior
      anaesthesiologist (AP) and the senior surgeon (JR), between 2000 and 2004. There
      were minimal complications associated with this technique in this series. The
      subglottic catheter never proved impossible to insert, and was used on one
      occasion in a rescue mode after supraglottic jetting led to oxygen desaturation.
      Body habitus did not prevent use of the technique in this series. There were only
      3 instances in the entire series (n=352) of cases requiring replacement by the
      supraglottic catheter due to limitation of visualization of the posterior
      glottis. The technique was used in a wide variety of surgical pathology, from
      benign hyperfunction-related laryngeal pathology, through paralytic vocal fold
      conditions, papilloma, granuloma, dysplasia and malignancy. Advantages and
      disadvantages over traditional intubation techniques and supraglottic jet
      ventilation are reviewed, including such issues as: ease of
      intubation/ventilation; surgical exposure/control; maintenance of O(2) and CO(2)
      levels; use in the limited/borderline airway.

PMID- 18344143
TI  - TKK Aparat: an environment for voice inverse filtering and parameterization.
AB  - The study of the glottal flow, the acoustic excitation for voiced speech,
      provides insight into the voice signal, which is of potential benefit in many
      disciplines. One common method for estimating the glottal flow is inverse
      filtering, in which the effects of the vocal tract and the lip radiation are
      removed from a microphone signal. This paper presents a new inverse filtering and
      parameterization software package, which is available under an open-source
      licence. It provides a user-friendly graphical interface for rapid inverse
      filtering and parameterization, and the algorithms and parameters can be easily
      re-used in other projects. The system has already proved to be useful in
      algorithm development, speech science research, as well as in the study of
      occupational voice.

PMID- 18344144
TI  - Barrels by the sea: Barrels XX meeting report.
AB  - The 20th annual Barrels meeting brought together researchers who utilize
      behavioral, physiological, anatomical, and molecular techniques to understand the
      structure and function of the barrel system. Barrels XX featured talks on the
      role inhibition has in shaping cortical responses within the barrel system, the
      molecular cues that influence the development of the whisker-to-barrel system,
      and the synaptic plasticity that can shape responses within the system. The
      meeting highlighted why the whisker-to-barrel system is an ideal model to
      investigate the development of cortical circuitry and how its functioning can
      influence behavioral responses.

PMID- 18344146
TI  - GAP-43 is critical for normal targeting of thalamocortical and corticothalamic,
      but not trigeminothalamic axons in the whisker barrel system.
AB  - Mice lacking the growth-associated protein GAP-43 (KO) show disrupted cortical
      topography and no barrels. Whisker-related patterns of cells are normal in the KO
      brainstem trigeminal complex (BSTC), while the pattern in KO ventrobasal thalamus
      (VB) is somewhat compromised. To better understand the basis for VB and cortical
      abnormalities, we used small placements of DiI to trace axonal projections
      between BSTC, VB, and barrel cortex in wildtype (WT) and GAP-43 KO mice. The
      trigeminothalamic (TT) pathway consists of axons from cells in the Nucleus
      Prinicipalis that project to the contralateral VB thalamus. DiI-labeled KO TT
      axons crossed the midline from BSTC and projected to contralateral VB normally,
      consistent with normal BSTC cytoarchitecture. By contrast, the KO thalamocortical
      axons (TCA) projection was highly abnormal. KO TCAs showed delays of 1-2 days in
      initial ingrowth to cortex. Postnatally, KO TCAs showed multiple pathfinding
      errors near intermediate targets, and were abnormally fasciculated within the
      internal capsule (IC). Interestingly, most individually labeled KO TCAs
      terminated in deep layers instead of in layer IV as in WT. This misprojection is
      consistent with birthdating analysis in KO mice, which revealed that neurons
      normally destined for layer IV remain in deep cortical layers. Early outgrowth of
      KO corticofugal (CF) axons was similar for both genotypes. However, at P7 KO CF
      fibers remained bundled as they entered the IC, and exhibited few terminal
      branches in VB. Thus, the establishment of axonal projections between thalamus
      and cortex are disrupted in GAP-43 KO mice.

PMID- 18344147
TI  - The tactile perception of stimulus orientation.
AB  - Studies of the visual system suggest that, at an early stage of form processing,
      a stimulus is represented as a set of contours and that a critical feature of
      these local contours is their orientation. Here, we characterize the ability of
      human observers to identify or discriminate the orientation of bars and edges
      presented to the distal fingerpad. The experiments were performed using a 400
      probe stimulator that allowed us to flexibly deliver stimuli across a wide range
      of conditions. Orientation thresholds, approximately 20 degrees on average,
      varied only slightly across modes of stimulus presentation (scanned or indented),
      stimulus amplitudes, scanning speeds, and different stimulus types (bars or
      edges). The tactile orientation acuity was found to be poorer than its visual
      counterpart for stimuli of similar aspect ratio, contrast, and size. This result
      stands in contrast to the equivalent spatial acuity of the two systems (at the
      limit set by peripheral innervation density) and to the results of studies of
      tactile and visual letter recognition, which show that the two modalities yield
      comparable performance when stimuli are scaled appropriately.

PMID- 18344148
TI  - Fingerprint lines may not directly affect SA-I mechanoreceptor response.
AB  - Understanding how skin microstructure affects slowly adapting type I (SA-I)
      mechanoreceptors in encoding edge discontinuities is fundamental to understanding
      our sense of touch. Skin microstructure, in particular papillary ridges, has been
      thought to contribute to edge and gap sensation. Cauna's 1954 model of touch
      sensibility describes a functional relationship between papillary ridges and edge
      sensation. His lever arm model proposes that the papillary ridge (exterior
      fingerprint line) and underlying intermediate ridge operate as a single unit,
      with the intermediate ridge acting as a lever which magnifies indentation imposed
      at the papillary ridge. This paper contests the validity of the lever arm model.
      While correctly representing the anatomy, this mechanism inaccurately
      characterizes the function of the papillary ridges. Finite element analysis and
      assessment of the critical anatomy indicate that papillary ridges have little
      direct effect on how SA-I receptors respond to the indentation of static edges.
      Our analysis supports a revised (stiff shell-elastic bending support)
      interpretation where the epidermis is split into two major layers with a stiff,
      deformable shell over an elastic bending support. Recent physiological,
      electrophysiological, and psychophysical findings support our conclusion that the
      function of the intermediate ridge is distinct from the function of the papillary
      ridge.

PMID- 18344149
TI  - Static mechanical allodynia (SMA) is a paradoxical painful hypo-aesthesia:
      observations derived from neuropathic pain patients treated with somatosensory
      rehabilitation.
AB  - The present study aimed at investigating the time span it takes to remove a
      static mechanical allodynia (SMA) in humans suffering from chronic peripheral
      neuropathic pain. Forty-three subjects were included in the study and, during
      somatosensory rehabilitation, their SMA territory was precisely mapped. They then
      underwent distant vibrotactile counter stimulation (DVCS) treatment. It was
      observed that, with DVCS, SMA disappeared in all cases, and was transformed into
      an underlying hypoaesthesia. It was found that the "tenderness to touch" symptom
      (which is SMA) was located in the same territory as the underlying hypoaesthesia,
      which was located on a part of the cutaneous territory of a partially damaged
      nerve. These results demonstrate that treating patients suffering from
      neuropathic pain with DVCS revealed a skin territory of denervation that was
      previously masked by SMA. Thus, SMA can be considered as a paradoxical painful
      hypoaesthesia. Furthermore, mapping SMA is a valuable source of information for
      our understanding of abnormal sensory processing in neuropathic pain patients. We
      conclude that the mapping of the zone of hypersensitivity on the skin in humans
      suffering from chronic peripheral neuropathic pain improves diagnosis. The
      mapping of the zone of hypersensitivity is a tool to presume which branch of the
      peripheral nerve is damaged. The location of the axonal lesions is at the
      periphery, while the mechanism of pain sensitization is probably central and
      referred peripherally to the skin by a painful hypoaesthesia.

PMID- 18344150
TI  - Association between carotid artery atherosclerosis and coronary artery disease in
      young females. Reference to sex hormone profile.
AB  - BACKGROUND: Atherosclerosis of coronary and peripheral arteries occurs rarely in
      premenopausal women. It has been postulated that sex hormones protect the
      vascular wall. AIM: To evaluate whether ultrasound assessment of the changes in
      the wall of carotid arteries provides any useful information on the severity of
      atherosclerosis of the coronary vessels as well as whether the atherosclerotic
      changes in the wall of carotid arteries are accompanied by oestrogen
      insufficiency in the premenopausal age. METHODS: The studied group consisted of
      65 regularly menstruating women: 21 with coronary artery disease (CAD) revealed
      by angiography or after myocardial infarction (mean age 44 years)--the CAD group;
      and 44 healthy woman (mean age 43 years)--the control group. The severity of
      atherosclerotic changes was determined based on computer-assisted measurement of
      the intima-media complex thickness (IMC-T) in the common carotid artery. In all
      women prospective measurement of sex hormone profile was done with enzymatic
      immunoassay: oestradiol at day 7-9 and day 19-21 of the menstrual cycle and
      follicle-stimulating hormone (FSH). RESULTS: The IMC-T value was greater in the
      CAD group than the control group (0.696+/-0.124 mm and 0.518+/-0.064 mm
      respectively, p=0.001). The IMC-T (>0.6 mm) was a good indicator of the
      occurrence of CAD (OR 15.6, 95% CI 3.65-71.1, p <0.0001), with a sensitivity of
      73.7% and a specificity of 84.8%. There was a negative correlation between
      oestradiol level at day 19-21 of the menstrual cycle and IMC-T (r=-0.28, p=0.05).
      CONCLUSIONS: The IMC-T value >0.6 mm was found to be a sensitive and specific
      ultrasound parameter that can be useful in detecting the presence of CAD in
      premenopausal women. The results of the study also suggest a possible association
      between hormonal profile and early atherosclerotic changes in carotid arteries in
      premenopausal women.

PMID- 18344151
TI  - Percutaneous peripheral interventions in patients with non-ST elevation acute
      coronary syndromes performed by interventional cardiologists: rationale and
      results.
AB  - BACKGROUND: The coexistence of peripheral artery disease (PAD) and multilevel
      atherosclerosis increases death and stroke rates in patients with coronary artery
      disease (CAD). Due to many comorbidities these patients are often treated
      conservatively without revascularisation. AIM: To investigate whether complex
      percutaneous cardiovascular interventions for CAD and PAD may improve prognosis
      and long-term outcome in this group of patients. METHODS: We studied consecutive
      patients treated for symptomatic CAD who also had chronic PAD. The primary cause
      of hospital admission for all our patients was non-ST elevation acute coronary
      syndrome (NSTE ACS). All percutaneous peripheral interventions were performed
      during one hospital stay (index hospitalisation). Major adverse cardio- and
      cerebrovascular events (MACCE) during follow-up were defined as follows: death
      (cardiac and non-cardiac), myocardial infarction (MI), urgent revascularisation
      (surgical or repeat PCI, peripheral percutaneous intervention), stroke/TIA or
      amputation. RESULTS: We performed 109 interventions in 78 consecutive patients
      with chronic peripheral artery stenoses and occlusions. The average age was
      61.5+/-8.6 years and the majority were males (80%). Preinterventional angiography
      showed occlusions that involved the common iliac artery in 28 (36%) patients, the
      external iliac artery in 16 (21%) patients, internal iliac artery in 2 (3%)
      patients, and superficial femoral artery in 63 (81%) patients. Stenting was
      performed in half of the patients with a mean stent length of 69.6+/-50.3 mm. An
      average number of 1.24+/-0.55 stents was used for each lesion. During a mean
      follow-up of 18 months (range 4 to 42), there were 4 deaths, 3 MIs, 13 repeated
      percutaneous peripheral interventions due to restenosis in previously treated
      peripheral lesions, two urgent coronary interventions, two ischaemic strokes, two
      TIAs and one amputation. The combined follow--up MACCE end-point occurred in 32%
      of patients. CONCLUSIONS: Patients with concomitant CAD and PAD could safely
      undergo percutaneous cardiovascular and peripheral interventions. Multilevel
      intervention is associated with a promising long-term follow-up.

PMID- 18344152
TI  - Concentration of BNP, endothelin 1, pro-inflammatory cytokines (TNF-alpha, IL-6)
      and exercise capacity in patients with heart failure treated with carvedilol.
AB  - BACKGROUND: Recent studies on the pathophysiology of heart failure indicate the
      role of neurohormones and immune and inflammatory processes as potential
      mechanisms involved in the pathogenesis and clinical course of chronic heart
      failure (CHF). AIM: To analyse the relationship between concentrations of brain
      natriuretic peptide (BNP), endothelin-1 (ET-1), inflammatory cytokines (TNF
      alpha, IL-6) and cardiopulmonary stress test parameters, and to evaluate their
      changes during carvedilol treatment. METHODS: The study included 86 patients (81
      men and 5 women) aged from 35 to 70 years (56.8+/-9.19) with symptomatic heart
      failure and left ventricular ejection fraction <40%, receiving an inhibitor of
      angiotensin II converting enzyme, diuretic and/or digoxin but not beta-blockers.
      All patients at baseline, and then at 3 and 12 months after treatment, underwent
      a panel of studies to assess functional capacity according to NYHA,
      echocardiographic and cardiopulmonary stress test (CPX) parameters, and serum
      concentrations of BNP, ET-1, TNF-alpha and IL-6. Before introducing carvedilol we
      found a weak relationship between concentrations of BNP, ET-1, IL-6 and decreased
      VO2 peak. RESULTS: At 12 months exercise tolerance was significantly improved
      (exercise stress testing prolonged by 143.9 s, p=0.001) and an increase in
      metabolic equivalent (MET) by 1.41 (p=0.001) was observed. The VO2 peak was
      nonsignificantly increased by a mean of 0.9 ml/kg/min. In patients with baseline
      VO2 peak <14 ml/kg/min the concentrations of ET-1 and TNF-alpha were
      significantly higher than in the remaining ones, and after treatment they were
      significantly reduced. In these patients VO2 peak%N was also significantly
      increased (39.5+/-7.5 vs. 50.1+/-15,0; p=0.013). The number of patients with VO2
      peak <14 ml/kg/min also significantly decreased from 39 to 21 (p=0.013).
      CONCLUSIONS: In patients with HF decreased value of VO2 peak is associated with
      LV systolic function disorders and increased levels of BNP, ET-1, TNF-alpha and
      IL-6. Chronic treatment with carvedilol improves LV systolic function, exercise
      tolerance and peak oxygen consumption and is associated with significant decrease
      of BNP, ET-1, TNF-alpha and IL-6 concentrations.

PMID- 18344153
TI  - Short- and long-term mortality in patients with ST-elevation myocardial
      infarction treated with different therapeutic strategies. Results from
      WIelkopolska REgional 2002 Registry (WIRE Registry).
AB  - BACKGROUND: Although primary coronary angioplasty seems to be the best treatment
      in acute myocardial infarction (MI), thrombolytic therapy still remains the most
      common reperfusion strategy particularly in smaller centers. Nowadays, different
      regional networks are developed to improve the treatment of patients with MI.
      AIM: To analyse the effects of different therapeutic strategies on 30-day and
      long-term mortality (median time 18.3 months) after ST-elevation MI (STEMI) in a
      population of 3 350 000 people from the Wielkopolska Region. METHODS: In 2002,
      3780 patients with STEMI entered the registry. Complete data were available for
      3564 (94.3%) patients. Depending on therapeutic strategies, patients were divided
      into five groups: the PCI group--direct percutaneous coronary angioplasty (PCI)
      in small cathlab, 'selected patients', n=381 (10.7%); the PA group--aged <70,
      treated with tissue plasminogen activator (rt-PA) up to 4 hours from the onset of
      chest pain, n=479 (13.4%); the IS group - invasive strategy in every patient, 24
      hour duty, setting of unselected patients with STEMI, n=989 (27.7%); the SK group
      -patients receiving standard streptokinase treatment up to 12 hours from the
      onset of chest pain, n=584 (16.4%); the NR group--no reperfusion therapy, n=1131
      (31.7%). RESULTS: The 30-day mortality rate in the groups above was: 3.15, 4.38,
      4.54, 9.25, and 12.5% respectively (p <0.001). Long-term mortality rate was: 4.2,
      9.4, 9.4, 14.4, and 18.50% respectively (p <0.001). The rate of urgent PCI in the
      PA group was 25% and in the SK group--11% (p <0.001). CONCLUSIONS: Treatment with
      rt-PA in patients under 70 years of age and up to 4 hours from pain onset may be
      an alternative to an invasive strategy. However, a quarter of those patients
      require urgent PCI. In long-term observation the mortality benefit can be clearly
      seen only in patients with early PCI.

PMID- 18344154
TI  - Myocardial infarction in the elderly. Clinical and therapeutic differences.
AB  - BACKGROUND: The progressive aging of society results in increased numbers of
      acute myocardial infarctions (MI) in the elderly. In the presence of huge
      progress in MI treatment, it seems to be reasonable to analyse clinical course
      and prognosis in the elderly with MI. AIM: To assess differences in clinical
      characteristics and treatment of MI between patients younger than 65 and the
      elderly. METHODS: A total of 491 patients over 65 and 398 patients younger than
      65 with acute MI between June 2005 and February 2006 were retrospectively
      analysed. RESULTS: In patients over 65 there was significantly higher prevalence
      of arterial hypertension and diabetes, as well as low left ventricular ejection
      fraction and advanced heart failure. The time from onset of symptoms to admission
      was longer in the older group. The rate of reperfusion therapy in the elderly was
      significantly lower, and the results of invasive treatment were poor.
      Antiplatelet treatment was less aggressive in this group. In-hospital and long
      term mortality were significantly higher in patients over 65, but the lowest in
      subjects undergoing invasive strategy. CONCLUSIONS: Risk factors in baseline
      characteristics and lower rate of invasive therapeutic strategy result in worse
      prognosis in patients over 65 with acute MI. A significant reduction in mortality
      due to the invasive approach should encourage wide implementation of this
      approach in the elderly.

PMID- 18344155
TI  - [Advanced symptomatic atrioventricular block as a complication after
      transcatheter occlusion of secundum atrial septal defect in a 40-year-old woman
      with prior left bundle branch block].
AB  - We report a case of a woman with a left bundle branch block and secundum atrial
      septal defect (ASD) who underwent transcatheter occlusion using Amplatzer device.
      The patient was treated with antiarrhythmic drugs because of paroxysmal atrial
      flutter. One and a half month later the patient developed a second degree
      atrioventricular block. Temporary pacing was introduced, followed by a dual
      chamber pacemaker implantation due to recurrent symptomatic atrioventricular
      block. An association between conduction disorders, the use of antiarrhythmic
      drugs and the complications after ASD closure is discussed.

PMID- 18344156
TI  - [Apical hypertrophic cardiomyopathy as a cause of cardiac insufficiency in an 84
      year-old woman--a case report].
AB  - Apical hypertrophic cardiomyopathy (ApHCM) is a unique form of hypertrophic
      cardiomyopathy first described in Japan in 1976. The typical features of ApHCM
      consist of 'giant' negative T waves in the ECG and a 'spade-like' configuration
      of the left ventricular cavity detected by imaging techniques. We describe a case
      of an 84-year-old female in whom heart failure was the first symptom of the
      disease.

PMID- 18344157
TI  - [Treprostinil therapy for distal chronic thromboembolic pulmonary hypertension].
AB  - We present a case of a 77-year-old female with distal chronic thromboembolic
      pulmonary hypertension. Diagnostic and therapeutic difficulties are discussed.
      Clinical and haemodynamic benefits resulting from treprostinil therapy added to
      continuous anticoagulation are shown.

PMID- 18344158
TI  - [Type A aortic intramural haematoma--clinical course in two patients].
AB  - Aortic intramural haematoma (AIH) is a variation of aortic dissection where blood
      collects within the aortic media without the presence of an intimal flap. The
      natural history of the disease has not yet been definitely established. Two cases
      of AIH type A are presented--an 81-year-old hypertensive male, and a 60-year-old
      male, both admitted to the hospital with sudden-onset severe chest pain. In both
      cases AIH type A was confirmed using computed tomography. One patient underwent
      successful conservative treatment, whereas another one had urgent surgery.

PMID- 18344159
TI  - [Arrhythmias and conduction disturbances in patients with connective tissue
      diseases].

PMID- 18344160
TI  - [Cardiomyopathy, asymptomatic dysfunction, acute and chronic heart failure--what
      does it mean in light of recent guidelines and statements?].

PMID- 18344161
TI  - [Ventricular fibrillation and Brugada-like ECG pattern during propafenone
      treatment].

PMID- 18344162
TI  - [Accessory mitral valve tissue as a cause of the subvalvular aortic stenosis].

PMID- 18344163
TI  - [Transient ST-segment elevation in a patient after myocardial infarction with
      normal coronary arteries].

PMID- 18344164
TI  - [Termination of atrio-ventricular reentrant tachycardia in a pregnant woman using
      transoesophageal atrial pacing and pharmacotherapy].
AB  - We describe a case of a 19-year-old pregnant woman with paroxysmal atrio
      ventricular reentrant tachycardia (AVNRT). Transoesophageal atrial pacing (TAP)
      successfully terminated the arrhythmia, however, AVNRT restarted after 20 min and
      was initiated by ventricular ectopy. Intravenous metoprolol effectively
      suppressed ventricular ectopy and AVNRT did not recur. A modification of the ESC
      algorithm, with the inclusion of pacing techniques to terminate AVNRT, is
      proposed.

PMID- 18344165
TI  - [Fibroblast growth factor 1 gene and essential hypertension--from the chromosomal
      region linked to blood pressure to renal glomerulus].

PMID- 18344166
TI  - [Knowledge of cardiovascular risk factors and recommended lifestyle modifications
      in patients after an acute coronary syndrome. The influence of short-term,
      stationary rehabilitation. Preliminary results].
AB  - BACKGROUND: Education on behavioural risk factors and lifestyle modification is
      one of the core components of comprehensive cardiac rehabilitation. AIM: To
      assess the level of knowledge of cardiovascular risk factors and recommended
      lifestyle changes in patients rehabilitated after an acute coronary syndrome
      (ACS). METHODS: The study group consisted of 31 consecutive patients (22 males,
      56.6+/-10.9 years) participating in short-term, early, comprehensive cardiac
      rehabilitation. On admission, at discharge and 3 months after discharge patients'
      knowledge was assessed with a questionnaire worked out by the authors. RESULTS:
      On admission, patients had poor knowledge of cardiovascular risk factors and
      recommended lifestyle modifications, especially concerning diabetes,
      hypertension, and diet. After completing the rehabilitation programme,
      significantly higher percentage of patients gave correct answers to questions
      concerning diabetes and cholesterol-rich diet as cardiovascular risk factors, and
      substitution of vegetable fat for animal fat as a lifestyle modification, and
      significantly higher proportion of patients gave the correct value for elevated
      systolic blood pressure. CONCLUSIONS: Patients after ACS have poor knowledge of
      cardiovascular risk factors and recommended lifestyle modifications. The level of
      knowledge improves after short-term, stationary cardiac rehabilitation; however,
      the degree of this improvement is not completely satisfactory.

PMID- 18344167
TI  - Serial and single-victim rapists: differences in crime-scene violence,
      interpersonal involvement, and criminal sophistication.
AB  - Three categories of crime-scene behaviors (violence, interpersonal involvement,
      and criminal sophistication) among a group of 22 serial and 22 single-victim
      rapists were studied. Findings indicate that serial rapists were more likely to
      display a higher level of criminally sophisticated behaviors to avoid detection,
      whereas single-victim rapists were more likely to behave violently and engage in
      some form of interpersonal involvement with their victims. Implications of these
      findings for investigation and for understanding offenders' behavior are
      discussed.

PMID- 18344168
TI  - Judicial gatekeeping and the social construction of the admissibility of expert
      testimony.
AB  - Content analysis of 192 U.S. District Court cases was conducted to investigate
      judges' evaluations of expert characteristics and evidence characteristics for
      toxicology, psychological/psychiatric, and damages testimony. Judges evaluated
      more expert characteristics, but not more evidence characteristics, as the number
      of months post-Daubert increased (Hypotheses 1 and 2). More evidence
      characteristics were evaluated when evidence was quantitatively rather than
      qualitatively based (Hypothesis 3). The greatest number of evidence
      characteristics examined was for toxicology evidence (Hypothesis 4). Fewer expert
      characteristics were evaluated for admissible evidence, but more evidence
      characteristics were evaluated for inadmissible evidence (Hypothesis 5). All
      analyses were significant at .05. Implications for judges, attorneys, and experts
      are discussed.

PMID- 18344169
TI  - Juvenile psychopathy and judicial decision making: an empirical analysis of an
      ethical dilemma.
AB  - In the burgeoning juvenile psychopathy literature, there is a debate on whether
      it is appropriate to apply this construct to youths. Some have suggested that
      labeling children/adolescents as psychopathic might result in negative
      consequences, such as being recommended for more restrictive placements. However,
      the scant evidence is equivocal. This study provides additional insights on this
      issue by assessing judicial perceptions and recommendations to a hypothetical
      case. Results indicate that psychopathy influenced perceptions of amenability
      (eta = .12) and dangerousness (eta = .25), and recommendations for placement (eta
      = .11). More specifically, youth who were both labeled as psychopathic and
      ascribed psychopathic traits were viewed as less amenable to treatment and more
      dangerous and were more likely to be recommended for a restrictive placement than
      youth who were neither labeled nor described as such. The effect of psychopathy
      on placement recommendations, however, was not significant after controlling for
      perceptions of dangerous. This suggests that the influence of psychopathy on
      judicial restrictiveness may operate through the perceived dangerousness of the
      youth.

PMID- 18344170
TI  - Relation between parenting stress and psychopathic traits among children.
AB  - Parenting stress was examined as a correlate of psychopathic traits, specifically
      narcissism, callous/unemotional traits, and impulsivity, among school-aged
      children while controlling for the variance explained by aggressive behavior.
      Participants included 212 children ranging from 6 to 12 years of age (M = 8.3
      years) who were admitted to an acute child psychiatric inpatient unit for
      treatment. Parents completed standardized measures of aggression (Child Behavior
      Checklist; CBCL), psychopathic traits (Antisocial Process Screening Device;
      APSD), and parenting stress (Parenting Stress Index; PSI) at the time of the
      child's admission. Multiple regression analyses revealed that high levels of the
      PSI dimension attachment difficulties were associated with high levels of
      narcissism and callous/unemotional traits among the children while statistically
      controlling for aggression. The PSI dimension role restriction was also found to
      be negatively related to narcissism. These findings suggest that specific aspects
      of parenting stress may be related to child psychopathic traits and might aid
      with conceptualizing and developing treatment approaches for childhood behavior
      problems.

PMID- 18344171
TI  - Anticipatory injustice among adolescents: age and racial/ethnic differences in
      perceived unfairness of the justice system.
AB  - The present study examines age differences in anticipatory injustice, or the
      expectation of unfair or discriminatory treatment in the legal system. 1,393
      adolescents and young adults from the community or from detention centers and
      jails were interviewed regarding demographic and justice system experience,
      intelligence, expectations about fair treatment, and legal decisions. African
      Americans and Latinos and those with more system experience expected greater
      injustice across multiple legal contexts. Anticipatory injustice increased with
      age among African Americans and those with the most system experience. It also
      predicted choices about police interrogation, attorney consultation, and plea
      agreements. Anticipations of injustice during adolescence may affect future
      interactions with court officials as well as more general constructs of legal
      socialization.

PMID- 18344172
TI  - Predictors of verdict and punitive damages in high-stakes civil litigation.
AB  - This research investigated demographic and attitudinal- psychological predictors
      of verdict and amount of punitive damages awarded in high-stakes civil
      litigation. Four hundred and forty-six surrogate jurors, selected to be
      representative of actual jurors, were exposed to realistic case presentations in
      insurance, tobacco, and pharmaceutical cases that were about to go to trial.
      Hierarchical regression revealed that perceptions of the existence of a
      litigation crisis predicted verdict in the tobacco and pharmaceutical cases after
      controlling for all other variables. Demographic variables predicted verdict and
      punitive damage awards only modestly and in different ways in the three cases.
      Need for cognition, strength of will and rationality, and a perception that there
      is a litigation crisis predicted the amount of punitive damages awarded in the
      tobacco case. Litigation crisis also predicted the amount of punitive damages
      awarded in the pharmaceutical case. Implications for jury selection are
      discussed.

PMID- 18344173
TI  - The determiner congruency effect in language production investigated with
      functional MRI.
AB  - In language production, naming a picture with a gender-marked determiner phrase
      is faster in the presence of a distractor noun with the same grammatical gender
      (congruent condition) as compared with a different grammatical gender
      (incongruent condition). We investigated the neural correlates of this determiner
      congruency effect in German with functional magnetic resonance imaging (fMRI).
      Participants named pictures of real objects with determiner phrases (e.g. "der
      Tisch"-the table) in the presence of a gender-congruent or gender-incongruent
      distractor noun. Different comparisons allow the following functional segregation
      within the prefrontal cortex. First, the comparison between picture naming versus
      rest revealed a steeper slope of the haemodynamic response function (HRF) in the
      gender-congruent than the gender-incongruent condition in the left BA 44,
      suggesting the involvement of BA 44 in determiner selection. HRF amplitude
      differences between the congruent and the incongruent condition were observed
      outside the language network in the right fronto-median wall (congruent >
      incongruent), and in the left premotor cortex, middle frontal gyrus, cerebellum,
      and inferior parietal lobe (incongruent > congruent). The latter regions are
      known to be involved in the processing of incongruence and conflict in general.
      The data thus reveal the involvement of the left BA 44 in the selection of
      determiners for language production.

PMID- 18344174
TI  - "Aha!": The neural correlates of verbal insight solutions.
AB  - What are the neural correlates of insight solutions? To explore this question we
      asked participants to perform an anagram task while in the fMRI scanner. Previous
      research indicates that anagrams are unique in that they can yield both insight
      and search solutions in expert subjects. Using a single-trial fMRI paradigm, we
      utilized the anagram methodology to explore the neural correlates of insight
      versus search solutions. We used both reaction time measures and subjective
      reports to classify each trial as a search or insight solution. Data indicate
      that verbal insight solutions activate a distributed neural network that includes
      bilateral activation in the insula, the right prefrontal cortex, and the anterior
      cingulate. These areas are discussed with their possible role in evaluation and
      metacognition of insight solutions, as well as attention and monitoring during
      insight.

PMID- 18344176
TI  - Large-scale neural model validation of partial correlation analysis for effective
      connectivity investigation in functional MRI.
AB  - Recent studies of functional connectivity based upon blood oxygen level dependent
      functional magnetic resonance imaging have shown that this technique allows one
      to investigate large-scale functional brain networks. In a previous study, we
      advocated that data-driven measures of effective connectivity should be developed
      to bridge the gap between functional and effective connectivity. To attain this
      goal, we proposed a novel approach based on the partial correlation matrix. In
      this study, we further validate the use of partial correlation analysis by
      employing a large-scale, neurobiologically realistic neural network model to
      generate simulated data that we analyze with both structural equation modeling
      (SEM) and the partial correlation approach. Unlike real experimental data, where
      the interregional anatomical links are not necessarily known, the links between
      the nodes of the network model are fully specified, and thus provide a standard
      against which to judge the results of SEM and partial correlation analyses. Our
      results show that partial correlation analysis from the data alone exhibits
      patterns of effective connectivity that are similar to those found using SEM, and
      both are in agreement with respect to the underlying neuroarchitecture. Our
      findings thus provide a strong validation for the partial correlation method.

PMID- 18344175
TI  - The neurophysiological bases of emotion: An fMRI study of the affective
      circumplex using emotion-denoting words.
AB  - OBJECTIVE: We aimed to study the neural processing of emotion-denoting words
      based on a circumplex model of affect, which posits that all emotions can be
      described as a linear combination of two neurophysiological dimensions, valence
      and arousal. Based on the circumplex model, we predicted a linear relationship
      between neural activity and incremental changes in these two affective
      dimensions. METHODS: Using functional magnetic resonance imaging, we assessed in
      10 subjects the correlations of BOLD (blood oxygen level dependent) signal with
      ratings of valence and arousal during the presentation of emotion-denoting words.
      RESULTS: Valence ratings correlated positively with neural activity in the left
      insular cortex and inversely with neural activity in the right dorsolateral
      prefrontal and precuneus cortices. The absolute value of valence ratings
      (reflecting the positive and negative extremes of valence) correlated positively
      with neural activity in the left dorsolateral and medial prefrontal cortex (PFC),
      dorsal anterior cingulate cortex, posterior cingulate cortex, and right dorsal
      PFC, and inversely with neural activity in the left medial temporal cortex and
      right amygdala. Arousal ratings and neural activity correlated positively in the
      left parahippocampus and dorsal anterior cingulate cortex, and inversely in the
      left dorsolateral PFC and dorsal cerebellum. CONCLUSION: We found evidence for
      two neural networks subserving the affective dimensions of valence and arousal.
      These findings clarify inconsistencies from prior imaging studies of affect by
      suggesting that two underlying neurophysiological systems, valence and arousal,
      may subserve the processing of affective stimuli, consistent with the circumplex
      model of affect.

PMID- 18344177
TI  - Masked smoking-related images modulate brain activity in smokers.
AB  - The questions of whether and how indiscriminate drug-related stimuli could
      influence drug-users are important to our understanding of addictive behavior,
      but the answers are still inconclusive. In the present preliminary functional
      magnetic resonance imaging study using a backward masking paradigm, the effect of
      indiscriminate smoking-related stimuli on 10 smokers and 10 nonsmokers was
      examined. The BOLD response showed a significant reduction (P = 0.001) in the
      right amygdala of smokers when they viewed but did not perceive masked smoking
      related stimuli, while no significant differences were found in the nonsmoker
      group. More voxels in anterior cingulate cortex were negatively correlated with
      the amygdala during the masked smoking-related picture condition in smokers but
      not in nonsmokers, whereas more positively correlated voxels were observed during
      the masked neutral condition. The BOLD response in drug-users indicates the
      amygdala responds to drug-related stimuli that are below the perceptual
      threshold. The functional connectivity data suggest a functional interaction
      between the amygdala and the anterior cingulate cortex when drug users view 33 ms
      back-masked drug-related stimuli. This observation suggests that the amygdala
      plays an important role in the indiscriminate drug-related cue process.

PMID- 18344178
TI  - Multi-rule quality control for the age-related eye disease study.
AB  - The Age-Related Eye Disease Study (AREDS), sponsored by the National Eye
      Institute, was designed to study the natural history and risk factors of age
      related macular degeneration (AMD) and cataract, and to evaluate the effect of
      high doses of antioxidants and zinc on eye disease progression. AMD and cataract
      are leading causes of visual impairment and blindness in the U.S., with frequency
      of both diseases increasing dramatically after age 65. Participants were randomly
      chosen to receive antioxidant or placebo tablets. Blood was drawn annually from a
      subset of patients, and serum concentrations of 17 different nutritional
      indicators were measured. Because of the complexity of the analytical methods,
      and possibility of instrument error due to failure of any one of many component
      parts, several different instruments were used for most analytes. In addition, to
      assure that the measurement systems were performing adequately across a wide
      range of concentrations, multiple control pools were monitored with analyte
      concentrations at low, medium, and high concentrations. We report here the multi
      rule quality control system (MRQCS) used during the later part of the trial
      (AREDS Phase III). This system was designed to monitor systematic error and
      random within- and among-run error for analytical runs using 1-3 different
      quality control pools per run and 1-2 measurements of each pool per run. We
      demonstrate the features of the MRQCS using quality control (QC) data associated
      with vitamin C measurements. We also provide operating characteristics to
      demonstrate how the MRQCS responds to increases in systematic and/or random
      error.

PMID- 18344179
TI  - Idiopathic thrombocytopenic purpura after colectomy for pediatric ulcerative
      colitis.

PMID- 18344180
TI  - Racial/ethnic disparities in vaccination coverage by 19 months of age: an
      evaluation of the impact of missing data resulting from record scattering.
AB  - We describe how trends in the vaccination coverage at 19 months of age vary by
      race/ethnicity; explore the extent to which data required to evaluate a child's
      up-to-date vaccination status is missing as a result of the scattering of
      vaccination records among many vaccination providers; evaluate how the prevalence
      of that missing data varies by race/ethnicity; and evaluate the impact that the
      missing data has on estimated race/ethnic disparities in vaccination coverage. We
      analyzed data from 255,043 children sampled between 1995 and 2006 by the National
      Immunization Survey (NIS). Among children who had 2+ vaccination providers
      reporting, estimated vaccination coverage was significantly lower by
      approximately 15 per cent among children who did not have all of their providers
      reporting to the NIS compared with children who had all of their vaccination
      providers reporting to the NIS. By comparing coverage estimates that were
      adjusted for missing data to unadjusted estimates, we found that unadjusted
      estimates consistently underestimated vaccination coverage by as much as 4.9 per
      cent for Asians, 4.8 per cent for Hispanics, 4.1 per cent for American
      Indian/Alaska Natives, 3.3 per cent for non-Hispanic blacks, and 2.8 per cent for
      non-Hispanic white children. Estimates of disparities in estimated vaccination
      coverage did not depend on whether coverage estimates were adjusted for missing
      data. Hispanic and non-Hispanic black children had estimated coverage rates that
      were significantly less than that of non-Hispanic white children, with median
      disparities of 4 and 9 per cent, respectively. Regardless of whether estimates
      are adjusted, data from the NIS show that disparities in vaccination coverage
      that existed in the early 1990s persist.

PMID- 18344181
TI  - Steroid and thyroid hormone receptors in mitochondria.
AB  - Receptors for glucocorticoids, estrogens, androgens, and thyroid hormones have
      been detected in mitochondria of various cell types by Western blotting,
      immunofluorescence labeling, confocal microscopy, and immunogold electron
      microscopy. A role of these receptors in mitochondrial transcription, OXPHOS
      biosynthesis, and apoptosis is now being revealed. Steroid and thyroid hormones
      regulate energy production, inducing nuclear and mitochondrial OXPHOS genes by
      way of cognate receptors. In addition to the action of the nuclearly localized
      receptors on nuclear OXPHOS gene transcription, a parallel direct action of the
      mitochondrially localized receptors on mitochondrial transcription has been
      demonstrated. The coordination of transcription activation in nuclei and
      mitochondria by the respective receptors is in part realized by their binding to
      common trans acting elements in the two genomes. Recent evidence points to a role
      of the mitochondrial receptors in cell survival and apoptosis, exerted by genomic
      and nongenomic mechanisms. The identification of additional receptors of the
      superfamily of nuclear receptors and of other nuclear transcription factors in
      mitochondria increases their arsenal of regulatory molecules and further
      underlines the central role of these organelles in the integration of growth,
      metabolic, and cell survival signals.

PMID- 18344182
TI  - Multidomain STS/TULA proteins are novel cellular regulators.
AB  - Proteins of the STS/TULA family recently emerged as important regulators of
      cellular functions. They exhibit a unique domain architecture, featuring at least
      three interactive/functional domains. Despite a significant degree of homology
      between the two members of this family, there are considerable functional
      differences between them. Thus, one of them is ubiquitously expressed in
      mammalian tissues and exhibits high phosphatase activity, whereas the other one
      is expressed in lymphocytes only and exhibits very low phosphatase activity, but
      is capable of promoting apoptosis, an activity unique for this family member.
      Among several functions reported for STS/TULA proteins, the most characterized
      one is the regulation of protein tyrosine kinase-mediated signaling.
      Interestingly, gene deletion of neither family member results in a discernible
      phenotype, whereas simultaneous deletion of both members causes hyperreactivity
      of T cells. Despite their apparent importance, the physiological role and the
      molecular basis of the effects of STS/TULA proteins remain poorly understood.
      This brief review summarizes what is currently known about the STS/TULA family
      and outlines the unresolved questions in this area.

PMID- 18344183
TI  - Eukaryotic selenoprotein synthesis: mechanistic insight incorporating new factors
      and new functions for old factors.
AB  - Selenium is an essential micronutrient that has been linked to various aspects of
      human health. Selenium exerts its biological activity through the incorporation
      of the amino acid, selenocysteine (Sec), into a unique class of proteins termed
      selenoproteins. Sec incorporation occurs cotranslationally at UGA codons in
      archaea, prokaryotes, and eukaryotes. UGA codons specify Sec coding rather than
      termination by the presence of specific secondary structures in mRNAs termed
      selenocysteine insertion (SECIS) elements, and trans-acting factors that
      associate with SECIS elements. Herein, we discuss the various proteins known to
      function in eukaryotic selenoprotein biosynthesis, including several players
      whose roles have only been elucidated very recently.

PMID- 18344184
TI  - Vascular endothelial growth factor is associated with histological instability of
      carotid plaques.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) promotes events favouring
      carotid plaque instability: inflammatory chemoattraction, thrombogenesis, and
      upregulation of matrix metalloproteinases and cell adhesion molecules. The aim of
      this study was to assess neovascularization, VEGF and its receptors in high-grade
      stable and unstable carotid plaques. METHODS: Immunohistochemical staining for
      CD34, VEGF, VEGF receptor (VEGFR) 1 and VEGFR2 was performed in 34 intact carotid
      endarterectomy specimens, and compared in sections demonstrating maximal
      histological instability (cap rupture/thinning) or, if stable, maximal stenosis.
      RESULTS: VEGF staining was increased in 12 unstable compared with 22 stable
      plaques (median (interquartile range, i.q.r.) plaque score 4.0 (4.0-4.0) versus
      3.0 (2.0-3.0); P = 0.002) with upregulation of VEGFR1 (plaque score 4.0 (2.0-4.0)
      versus 2.0 (1.0-3.0); P = 0.016). In unstable plaques this was associated with
      increased microvessel density in the cap (median (i.q.r.) 12.1 (4.0-30.0) versus
      1.1 (0.0-7.3) microvessels/mm(2); P = 0.017) and shoulder regions (7.7 (3.4-21.4)
      versus 3.1 (0.4-10.8) microvessels/mm(2); P = 0.176). CONCLUSION: Increased VEGF
      and receptor staining were seen in histologically unstable carotid plaques.
      Although these differences could reflect cytokine-driven inflammatory events
      accompanying plaque instability, VEGF and VEGFR1 could be key mediators.

PMID- 18344185
TI  - A statistical methodology for drug-drug interaction surveillance.
AB  - Interaction between drug substances may yield excessive risk of adverse drug
      reactions (ADRs) when two drugs are taken in combination. Collections of
      individual case safety reports (ICSRs) related to suspected ADR incidents in
      clinical practice have proven to be very useful in post-marketing surveillance
      for pairwise drug--ADR associations, but have yet to reach their full potential
      for drug-drug interaction surveillance. In this paper, we implement and evaluate
      a shrinkage observed-to-expected ratio for exploratory analysis of suspected drug
      drug interaction in ICSR data, based on comparison with an additive risk model.
      We argue that the limited success of previously proposed methods for drug-drug
      interaction detection based on ICSR data may be due to an underlying assumption
      that the absence of interaction is equivalent to having multiplicative risk
      factors. We provide empirical examples of established drug-drug interaction
      highlighted with our proposed approach that go undetected with logistic
      regression. A database wide screen for suspected drug-drug interaction in the
      entire WHO database is carried out to demonstrate the feasibility of the proposed
      approach. As always in the analysis of ICSRs, the clinical validity of hypotheses
      raised with the proposed method must be further reviewed and evaluated by subject
      matter experts.

PMID- 18344186
TI  - 'Mendelian randomization' equals instrumental variable analysis with genetic
      instruments.
AB  - Interest in instrumental variable (IV) analyses using genetic instruments has
      been growing over the past 4 years. The background, strength and weaknesses of
      this approach, which in the epidemiology literature has been referred to as
      'Mendelian randomization', has been recently reviewed by Lawlor et al. (Statist.
      Med. 2007. DOI: 10.1002/sim.3034). We suggest a change in the nomenclature of
      'Mendelian randomization' and discuss issues relevant to IV analysis including
      instrument validation, motivation of IV analysis and interpretation of IV
      estimates in order to motivate a more consistent and standard use of IV analysis
      across applications using genetic instruments.

PMID- 18344187
TI  - Critical aspects of the Bayesian approach to phase I cancer trials.
AB  - The Bayesian approach to finding the maximum-tolerated dose in phase I cancer
      trials is discussed. The suggested approach relies on a realistic dose-toxicity
      model, allows one to include prior information, and supports clinical decision
      making by presenting within-trial information in a transparent way. The modeling
      and decision-making components are flexible enough to be extendable to more
      complex settings. Critical aspects are emphasized and a comparison with the
      continual reassessment method (CRM) is performed with data from an actual trial
      and a simulation study. The comparison revealed similar operating characteristics
      while avoiding some of the difficulties encountered in the actual trial when
      applying the CRM.

PMID- 18344188
TI  - Mesh for hernia repair.

PMID- 18344189
TI  - SWAP-70 is important for invasive phenotypes of mouse embryo fibroblasts
      transformed by v-Src.
AB  - SWAP-70 is a protein involved in actin rearrangement, especially in membrane
      ruffling. Mouse embryo fibroblasts (MEFs) deficient in SWAP-70 show impaired
      membrane ruffling and fail to grow in soft agar after transformation by v-Src.
      Here, we show that v-Src transformed MEFs expressing SWAP-70 are highly invasive.
      MEFs expressing SWAP-70 or v-Src alone were far less invasive, suggesting that
      both proteins were required for the cells to be invasive. Expression of both SWAP
      70 and v-Src induced constant membrane ruffling, which may cause vigorous cell
      movement, probably required for invasiveness of the cells. Expression of v-Src
      alone morphologically transformed MEFs but formed lamellipodia rather than
      membrane ruffles, suggesting less aggressive nature of the cells compared with
      those expressing both SWAP-70 and v-Src. These results suggest that v-Src and
      SWAP-70 act synergistically in the invasion activity of MEFs.

PMID- 18344190
TI  - How I became a biochemist.

PMID- 18344191
TI  - Early dissociation of face and object processing: a magnetoencephalographic
      study.
AB  - The early dissociation in cortical responses to faces and objects was explored
      with magnetoencephalographic (MEG) recordings and source localization. To control
      for differences in the low-level stimulus features, which are known to modulate
      early brain responses, we created a novel set of stimuli so that their
      combinations did not have any differences in the visual-field location, spatial
      frequency, or luminance contrast. Differing responses to face and object (flower)
      stimuli were found at about 100 ms after stimulus onset in the occipital cortex.
      Our data also confirm that the brain response to a complex visual stimulus is not
      merely a sum of the responses to its constituent parts; the nonlinearity in the
      response was largest for meaningful stimuli.

PMID- 18344192
TI  - Vinylic telluride derivatives as promising pharmacological compounds with low
      toxicity.
AB  - The aim of the present study was to evaluate pharmacological and toxicological
      properties of (Z)-2-(methylthio)-1-(butyltelluro)-1-phenylethene 1a, (Z)-1-(4
      methylphenylsulfonyl)-2-(phenyltelluro)-2-phenylethene 1b, (Z)-2-(butyltelluro)-1
      (benzylthio)-1-heptene 1c and (Z)-2-(phenylthio)-1-(butyltelluro)-1-phenylethene
      1d. In vitro, vinylic telluride derivatives 1a, 1d and 1c were more effective in
      reducing lipid peroxidation than compound 1b. The maximal inhibitory effect of
      vinylic telluride derivatives on lipid peroxidation was in the following order:
      1a = 1d > 1c > 1b. Compound 1b was more potent in inhibiting delta-ALA-D activity
      (delta-aminolevulinate dehydratase) than compounds 1c and 1d. Based on the in
      vitro properties presented by compounds 1a (an antioxidant) and 1b (a pro
      oxidant), toxicological parameters were assessed in vivo and ex vivo in rats.
      Calculated LD50 of compounds 1a and 1b, administered by oral route, were 20.5 and
      1.44 micromol kg(-1), respectively. Compound 1b induced behavioral alterations in
      the open field test. Renal and spleenic delta-ALA-D activities were inhibited in
      rats treated orally with compound 1a. Compound 1b stimulated delta-ALA-D activity
      in liver and spleen of rats. Rats treated with compound 1b had increased hepatic,
      renal and spleenic lipid peroxidation. Renal and hepatic markers were not altered
      when compounds 1a and 1b were administered to rats at doses of around LD50, while
      compound 1a at high doses changed aspartate aminotransferase activity and urea
      levels. Based on in vitro results, this study demonstrated that compounds 1a and
      1d are promising antioxidant compounds. Ex vivo data reinforce compound 1a as a
      promising drug for more detailed pharmacological studies.

PMID- 18344193
TI  - Cortical and subcortical correlates of functional electrical stimulation of wrist
      extensor and flexor muscles revealed by fMRI.
AB  - The main scope of this study was to test the feasibility and reliability of FES
      in a MR-environment. Functional Electrical Stimulation (FES) is used in the
      rehabilitation therapy of patients after stroke or spinal cord injury to improve
      their motor abilities. Its principle lies in applying repeated electrical
      stimulation to the relevant nerves or muscles for eliciting either isometric or
      concentric contractions of the treated muscles. In this study we report cerebral
      activation patterns in healthy subjects undergoing fMRI during FES stimulation.
      We stimulated the wrist extensor and flexor muscles in an alternating pattern
      while BOLD-fMRI was recorded. We used both block and event-related designs to
      demonstrate their feasibility for recording FES activation in the same cortical
      and subcortical areas. Six out of fifteen subjects repeated the experiment three
      times within the same session to control intraindividual variance. In both block
      and event-related design, the analysis revealed an activation pattern comprising
      the contralateral primary motor cortex, primary somatosensory cortex and premotor
      cortex; the ipsilateral cerebellum; bilateral secondary somatosensory cortex, the
      supplementary motor area and anterior cingulate cortex. Within the same subjects
      we observed a consistent replication of the activation pattern shown in
      overlapping regions centered on the peak of activation. Similar time course
      within these regions were demonstrated in the event-related design. Thus, both
      techniques demonstrate reliable activation of the sensorimotor network and
      eventually can be used for assessing plastic changes associated with FES
      rehabilitation treatment.

PMID- 18344194
TI  - Are flavonoids agonists or antagonists of the natural hormone 17beta-estradiol?

PMID- 18344196
TI  - Effect of inflammation on kidney function and pharmacokinetics of COX-2 selective
      nonsteroidal anti-inflammatory drugs rofecoxib and meloxicam.
AB  - Chronic arthritis adversely affects glomerular function and nonsteroidal anti
      inflammatory drugs (NSAIDs) reduce electrolyte urinary excretion. In addition,
      both acute and chronic inflammations may alter clearance of drugs. We studied (a)
      the effects of inflammation on the renal function and pharmacokinetics of
      rofecoxib and meloxicam; (b) whether inflammation could exacerbate reduced
      electrolytes excretion changes observed with NSAIDs; and (c) the influence of
      inflammation on distribution of these drugs into the kidney. Single oral doses of
      rofecoxib (10 mg kg(-1)), meloxicam (3 mg kg(-1)) or placebo were administered to
      normal or pre-adjuvant arthritic rats. Blood and urine samples were collected for
      the measurement of plasma nitrite, BUN and creatinine. The urinary excretion of
      sodium and potassium was also determined. Nitrite, BUN and plasma creatinine were
      increased starting on day 9 in the groups with inflammation. Sodium and potassium
      excretion rates were not affected by inflammation. Meloxicam did not alter the
      electrolyte excretion in any of the groups. Rofecoxib significantly decreased
      sodium and potassium excretion in normal rats and potassium excretion in inflamed
      rats. Inflammation significantly increased plasma concentrations of rofecoxib,
      but not meloxicam. The ratios of the kidney:plasma concentrations were not
      significantly altered by inflammation following either drug. Inflammation altered
      kidney function, demonstrated by increases in BUN and plasma creatinine. However,
      it did not influence the urinary electrolytes excretion. Since we have observed
      similar patterns of the effect of NSAIDs on kidney under healthy and inflammatory
      conditions, one may conclude that inflammation does not exacerbate the adverse
      effect.

PMID- 18344197
TI  - Combined treatment with naringin and vitamin C ameliorates streptozotocin-induced
      diabetes in male Wistar rats.
AB  - Diet and nutrition have substantial impact on reducing the incidence of diabetes
      mellitus, where oxidative stress is an important etiopathological factor. The
      combined protective role of low dose of naringin (15 mg kg(-1)) and vitamin C (25
      mg kg(-1)) and high dose of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1))
      on streptozotocin (STZ)-induced toxicity was studied in male Wistar rats. To
      induce type II diabetes mellitus, rats were injected with STZ intraperitoneally
      at a dose of 45 mg kg(-1) body weight. STZ-induced diabetic rats showed
      significant increase in blood glucose, water intake, food intake and glycated
      hemoglobin and significant decrease in plasma insulin, total hemoglobin, body
      weight and liver glycogen. Diabetic rats also showed significant decrease in the
      activity of hexokinase and significant increase in the activities of glucose-6
      phosphatase and fructose-1,6-bisphosphatase in liver and kidney. The levels of
      plasma thiobarbituric acid reactive substances, lipid hydroperoxides and vitamin
      E were elevated while the level of reduced glutathione was decreased in diabetic
      rats. Glycoprotein components such as hexose, hexosamine, fucose and sialic acid
      were increased in plasma, liver and kidney of diabetic rats. Oral administration
      of high doses of naringin (30 mg kg(-1)) and vitamin C (50 mg kg(-1)) to diabetic
      rats for a period of 21 days normalized all the above-mentioned biochemical
      parameters. The effect exerted by naringin (30 mg kg(-1)) and vitamin C (50 mg
      kg(-1)) was similar to the effect exerted by insulin (6 units kg(-1)). Thus, our
      study shows the antihyperglycemic and antioxidant effects of naringin and vitamin
      C in STZ-induced type II diabetes mellitus in rats.

PMID- 18344198
TI  - In vitro oxime protection of human red blood cell acetylcholinesterase inhibited
      by diisopropyl-fluorophosphate.
AB  - Oximes are enzyme reactivators used in treating poisoning with organophosphorus
      cholinesterase (AChE) inhibitors. The oxime dose which can be safely administered
      is limited by the intrinsic toxicity of the substances such as their own AChE
      inhibiting tendency. Clinical experience with the available oximes is
      disappointing. To meet this need, new AChE reactivators of potential clinical
      utility have been developed. The purpose of the study was to estimate in vitro
      both the intrinsic toxicity and the extent of possible protection conferred by
      established (pralidoxime, obidoxime, HI-6, methoxime, trimedoxime) and
      experimental (K-type) oximes, using diisopropyl-fluoro-phosphate (DFP) as an AChE
      inhibitor. The IC50 of DFP against human red blood cell AChE was determined (
      approximately 120 nm). Measurements were then repeated in the presence of
      increasing oxime concentrations, leading to an apparent increase in DFP IC50.
      Calculated IC50 values were plotted against oxime concentrations to obtain an
      IC50 shift curve. The slope of this shift curve (tan alpha) was used to quantify
      the magnitude of the protective effect (nm IC50 increase per microm oxime). We
      show that, in the case of a linear relationship between oxime concentration and
      IC50, the binding constant K, determined using the Schild equation, equals
      IC50/DFP/tan alpha. Based on the values of tan alpha and of the binding constant
      K, some of the new K-oxime reactivators are far superior to pralidoxime (tan
      alpha = 0.8), obidoxime (1.5), HI-6 (0.8), trimedoxime (2.9) and methoxime (5.9),
      with K-107 (17), K-108 (20), and K-113 (16) being the outstanding compounds.

PMID- 18344199
TI  - Role of hematopoietic microenvironment in prolonged impairment of B cell
      regeneration in age-related stromal-cell-impaired SAMP1 mouse: effects of a
      single dose of 5-fluorouracil.
AB  - In this study, we examined the age-associated defect of stromal cells, which
      support B cell development, treated with 5-fluorouracil (5-FU) to induce severe
      perturbation of hematopoiesis, including B lymphocyte development, using SAMP1
      mice exhibiting senescence-mimicking stromal-cell impairment after 30 weeks of
      age. Significant findings of this study are as follows: first, a marked and
      prolonged decrease in number of CFU-preB cells in non-SCI mice (58% of the steady
      state level) associated with more markedly depressed number of CFU-preB cells in
      SCI mice (20% of the steady-state level), despite the absence of difference in
      the number of CFU-GMs during the period; second, in the non-SCI mice, a
      significant and prolonged up-regulation of GM-CSF and IL-6, positive regulators
      of myelopoiesis and suppressive factors of B lymphopoiesis, was observed. In SCI
      mice, greater and prolonged suppression of B lymphopoiesis was clearly
      demonstrated by the significant up-regulation of the negative regulator TNF-alpha
      associated with the concomitant marked down-regulation of the positive regulator
      SDF-1, although the increases of GM-CSF and IL-6 were limited. That is, 'negative
      complementation' makes preB recovery after 5-FU treatment impaired and prolonged.
      Principal component analysis clearly showed differences in the cytokine
      expression patterns in both early and later phases and the time course of the
      expression pattern of each cytokine between SCI and non-SCI mice without
      supervising information. An impaired regulation of the expressions of not only
      positive but also negative regulators after 5-FU treatment was, in part, the
      cause of the impaired regeneration of CFU-preB cells in SCI mice.

PMID- 18344200
TI  - Microwave assisted extraction for the determination of ethyl glucuronide in urine
      by gas chromatography-mass spectrometry.
AB  - Alcohol is the most frequently abused 'addictive substance' that causes serious
      social problems throughout the world; thus alcoholism is of particular interest
      in clinical and forensic medicine. Ethyl glucuronide (EtG) is a marker of recent
      alcohol consumption that detects alcohol use reliably over a definite time
      period. The present paper describes a new method for the determination of EtG in
      urine. It was based both on microwave assisted extraction (MAE) to extract the
      analyte from urine samples, and gas chromatography-mass spectrometry (GC-MS) to
      identify and quantify the EtG in selected ion monitoring (SIM) mode. The method
      was applied to 33 urine samples from alcohol users, obtaining positive results in
      all cases. It was fully validated including a linear range (0.1-100 microg ml(
      1)) and the main precision parameters. In summary, the use of microwave assisted
      extraction turned out to be a substantially simpler, faster and more sensitive
      procedure than any other conventional sample preparations.

PMID- 18344201
TI  - Inhibition by vitamin C of apoptosis induced by N-nitrosamines in HepG2 and HL-60
      cells.
AB  - The aim of this study was to evaluate the effect of vitamin C towards N
      nitrosopyrrolidine (NPYR)- and N-nitrosodimethylamine (NDMA)-induced apoptosis in
      human hepatoma (HepG2) and leukemia (HL-60) cell lines using flow cytometry
      analysis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labelling assay (TUNEL). None of the vitamin C concentrations tested (1-100
      microM) caused cytotoxicity in HepG2 cells. However, there were significant
      losses of HL-60 cells viability, measured by MTT assay, 72 h after treatment with
      50 and 100 microM vitamin C (29 and 46%, respectively). Moreover, an increase of
      lactate dehydrogenase release was significant with 50 microM at 72 h (28%) and
      with 100 microM of vitamin C at 48 and 72 h (27 and 36%, respectively). Also, the
      percentage of apoptotic HL-60 cells found in TUNEL assay increased to 21% when
      they were treated with 100 microM vitamin C for 72 h. Thus, in subsequent
      simultaneous treatments with NPYR (30 and 50 mM) or NDMA (27 and 68 mM) and
      vitamin C, concentrations of 5-50 microM vitamin C were used. Our results
      revealed that vitamin C, at all concentrations and times tested, reduced the
      apoptosis induced by NPYR and NDMA in both cell lines, showing a similar effect
      in HepG2 and HL-60 cells towards NPYR (50 mM)--65 and 63% of reduction,
      respectively--whereas towards NDMA (27 mM) the inhibition was higher in HL-60
      than in HepG2 cells--75 and 57%, respectively. Therefore, our findings suggest
      that inhibition of apoptosis may be one of the mechanisms by which vitamin C
      exerts its protective effect.

PMID- 18344203
TI  - Molecular mechanism of preconditioning.
AB  - During the last 20 years, since the appearance of the first publication on
      ischemic preconditioning (PC), our knowledge of this phenomenon has increased
      exponentially. PC is defined as an increased tolerance to ischemia and
      reperfusion induced by previous sublethal period ischemia. This is the most
      powerful mechanism known to date for limiting the infract size. This adaptation
      occurs in a biphasic pattern (i) early preconditioning (lasts for 2-3 h) and (ii)
      late preconditioning (starting at 24 h lasting until 72-96 h after initial
      ischemia). Early preconditioning is more potent than delayed preconditioning in
      reducing infract size. Late preconditioning attenuates myocardial stunning and
      requires genomic activation with de novo protein synthesis. Early preconditioning
      depends on adenosine, opioids and to a lesser degree, on bradykinin and
      prostaglandins, released during ischemia. These molecules activate G-protein
      coupled receptor, initiate activation of K(ATP) channel and generate oxygen-free
      radicals, and stimulate a series of protein kinases, which include protein kinase
      C, tyrosine kinase, and members of MAP kinase family. Late preconditioning is
      triggered by a similar sequence of events, but in addition essentially depends on
      newly synthesized proteins, which comprise iNOS, COX-2, manganese superoxide
      dismutase, and possibly heat shock proteins. The final mechanism of PC is still
      not very clear. The present review focuses on the possible role signaling
      molecules that regulate cardiomyocyte life and death during ischemia and
      reperfusion.

PMID- 18344204
TI  - The role of PAS kinase in regulating energy metabolism.
AB  - Metabolic disorders, such as diabetes and obesity, are fundamentally caused by
      cellular energy imbalance and dysregulation. Therefore, understanding the
      regulation of cellular fuel and energy metabolism is of great importance to
      develop effective therapies for metabolic disease. The cellular nutrient and
      energy sensors, AMPK and TOR, play a key role in maintaining cellular energy
      homeostasis. Like AMPK and TOR, PAS kinase (PASK) is also a nutrient responsive
      protein kinase. In yeast, PAS kinase phosphorylates the enzyme Ugp1 and thereby
      shifts glucose partitioning toward cell wall glucan synthesis at the expense of
      glycogen synthesis. Consistent with this function, yeast PAS kinase is activated
      by both cell integrity stress and growth in non-fermentative carbon sources. PASK
      is also important for proper regulation of glucose metabolism in mammals at both
      the hormonal and cellular level. In cultured pancreatic beta-cells, PASK is
      activated by elevated glucose concentrations and is required for glucose
      stimulated transcription of the insulin gene. PASK knockdown in cultured
      myoblasts causes increased glucose oxidation and elevated cellular ATP levels.
      Mice lacking PASK exhibit increased metabolic rate and resistance to diet-induced
      obesity. Interestingly, PGC-1 expression and AMPK and TOR activity were not
      affected in PASK deficient mice, suggesting PASK may exert its metabolic effects
      through a new mechanism. We propose that PASK plays a significant role in
      nutrient sensing, metabolic regulation, and energy homeostasis, and is a
      potential therapeutic target for metabolic disease.

PMID- 18344205
TI  - Bioanalytical methods for the determination of antipsychotic drugs.
AB  - Antipsychotic drugs are popular for the treatment of schizophrenia and other
      psychoses. In general, antipsychotics are administered in oral doses of only a
      few milligrams per day and they are widely metabolized in the body. Therefore,
      the concentration of these drugs in plasma is very low (pg-ng/mL levels). In
      addition, therapeutic drug monitoring (TDM) of antipsychotic drugs has proven to
      be of notable value for determining poor compliance of patients and addressing
      the challenges associated with considerable genetic variability in their
      metabolism. Thus, in order to conduct pharmacology and toxicology studies and
      clinical TDM of antipsychotics, as well as address the challenges associated with
      polypharmacy and drug metabolism, highly sensitive, selective and accurate
      bioanalytical methods are essential. The most recent studies on the determination
      of antipsychotics will be reviewed, including separation techniques, sample
      pretreatment, detectors and validation.

PMID- 18344206
TI  - Incomplete cellular depopulation may explain the high failure rate of bovine
      ureteric grafts.
AB  - BACKGROUND: The aim was to assess the results of a decellularized bovine ureter
      graft (SynerGraft) for complex venous access. METHODS: Bovine ureter conduits
      were implanted in patients with a failed fistula or access graft in whom native
      vessels were unsuitable as conduits. Graft histories were obtained from all
      patients who had undergone this procedure at one institution. Failed grafts were
      explanted and subjected to histological examination. A sample of fresh bovine
      ureter was immunostained for galactose (alpha1 --> 3) galactose (alpha-Gal).
      RESULTS: Nine patients with a median age of 46 (range 25-70) years underwent
      complex venous access surgery between August 2004 and November 2006 using a
      SynerGraft. Graft types included loop superficial femoral artery to stump of long
      saphenous vein (four patients), loop brachial artery to vein (two), brachial
      artery to axillary vein (two) and left axillary artery to innominate vein (one).
      Three grafts developed aneurysmal dilatation and two thrombosed. Histological
      assessment of the explanted bovine ureters revealed acute and chronic transmural
      inflammation. Immunostaining of fresh bovine ureter suggested residual cells and
      the xenoantigen alpha-Gal. CONCLUSION: Graft failure with aneurysmal dilatation
      and thrombosis in complex arteriovenous conduits using bovine ureter may be due
      to residual xenoantigens.

PMID- 18344207
TI  - A population-based study of craniosynostosis in metropolitan Atlanta, 1989-2003.
AB  - Craniosynostosis is a birth defect characterized by premature fusion of one or
      more cranial sutures. We describe the birth prevalence of craniosynostosis and
      related risk factors among infants born to residents of metropolitan Atlanta
      during 1989-2003. Data from the Metropolitan Atlanta Congenital Defects Program
      (MACDP) were used to identify infants with craniosynostosis. Case records with a
      code for craniosynostosis were reviewed to substantiate the diagnosis of
      craniosynostosis and to classify infants as having isolated craniosynostosis (no
      other unrelated major defects), multiple defects (one or more additional major,
      unrelated defects), or a syndrome (recognized or strongly suspected single-gene
      condition or chromosome abnormality). Vital records data on births of Georgia
      residents were used to analyze craniosynostosis prevalence by year of birth,
      maternal race and age, parity, plurality, and infants' sex, birth weight, and
      gestational age. We identified 281 infants born with craniosynostosis in
      metropolitan Atlanta during 1989-2003: 84% with isolated craniosynostosis, 7%
      with multiple defects, and 9% with syndromes. The birth prevalence was 4.3 per
      10,000 births, results consistent with findings from other population-based
      studies using similar case definitions. Apert syndrome was diagnosed in 40% of
      the syndromic cases, and sagittal synostosis was diagnosed in 39% of the cases of
      nonsyndromic craniosynostosis. Maternal age 35 years or older, multiple birth,
      male sex, and birth weight >4,000 g were risk factors for craniosynostosis.

PMID- 18344208
TI  - Hyperpolarized 3He apparent diffusion coefficient MRI of the lung:
      reproducibility and volume dependency in healthy volunteers and patients with
      emphysema.
AB  - PURPOSE: To measure the apparent diffusion coefficient (ADC) of hyperpolarized
      (HP) (3)He gas using diffusion weighted MRI in healthy volunteers and patients
      with emphysema and examine the reproducibility and volume dependency. MATERIALS
      AND METHODS: A total of eight healthy volunteers and 16 patients with emphysema
      were examined after inhalation of HP (3)He gas mixed with nitrogen (N(2)) during
      breathhold starting from functional residual capacity (FRC) in supine position.
      Coronal diffusion-sensitized MR images were acquired. Each subject was imaged on
      three separate days over a seven-day period and received two different volumes
      (6% and 15% of total lung capacity [TLC]) of HP (3)He each day. ADC maps and
      histograms were calculated. The mean and standard deviation (SD) of the ADC at
      different days and volumes were compared. RESULTS: The reproducibility of the
      mean ADC and SD over several days was good in both healthy volunteers and
      patients (SD range of 0.003-0.013 cm(2)/second and 0.001-0.009 cm(2)/second at 6%
      and 15% of TLC for healthy volunteers, and a SD range of 0.001-0.041 cm(2)/second
      and 0.001-0.011 cm(2)/second, respectively, for patients). A minor but
      significant increase in mean ADC with increased inhaled gas volume was observed
      in both groups. CONCLUSION: Mean ADC and SD of HP (3)He MRI is reproducible and
      discriminates well between healthy controls and patients with emphysema at the
      higher gas volume. This method is robust and may be useful to gain new insights
      into the pathophysiology and course of emphysema.

PMID- 18344210
TI  - Partial splenic embolization for cancer patients with thrombocytopenia requiring
      systemic chemotherapy.
AB  - BACKGROUND: Partial splenic embolization (PSE) has been used to improve
      hematologic parameters related to hypersplenism. The purpose of this study was to
      review our institutional experience with PSE for cancer patients with
      thrombocytopenia because of splenic sequestration precluding the administration
      of systemic therapy (ST). METHODS: A retrospective review of cancer patients
      undergoing PSE was undertaken. Twenty-eight patients underwent PSE to correct
      thrombocytopenia to facilitate the initiation or resumption of ST. Primary and
      secondary endpoints of the current study included a platelet count increase > 150
      K/UL and the initiation of ST, respectively. Periprocedural laboratory values and
      adverse events were recorded. RESULTS: Thirty PSEs were performed in 28 patients.
      Two patients underwent repeat PSE because of recurrent thrombocytopenia after the
      successful initiation of ST. For procedures with adequate follow-up, primary and
      secondary endpoints were achieved in 96.3% (26 of 27 patients) and 95.7% (22 of
      23 patients) of patients, respectively. The mean platelet count was 81 K/UL
      immediately before PSE and peaked at 293 K/UL after PSE. For 23 patients with
      frequent laboratory follow-up, the mean time to a platelet count > 150 K/UL was
      10 days. The mean hospital stay was 4.5 days. Postprocedure abdominal pain
      occurred in all patients. Fever was documented in 16 patients and pulmonary
      consolidation/atelectasis or effusion was documented in 10 patients; 9 patients
      received empiric antibiotic coverage. The median overall survival was 9.40 months
      (95% confidence interval, 8.2-10.7 months) among the 28 patients after PSE.
      CONCLUSIONS: PSE is a safe and effective means of managing thrombocytopenia
      secondary to hypersplenism to facilitate the administration of ST in patients
      with cancer.

PMID- 18344211
TI  - Endometrioid epithelial ovarian cancer : 20 years of prospectively collected data
      from a single center.
AB  - BACKGROUND: Clinicopathological features and outcome of women with endometrioid
      and serous ovarian adenocarcinoma were compared. METHODS: Between 1984 and 2004,
      baseline and follow-up data were prospectively recorded on 1545 patients with
      ovarian cancer. Of these, 270 had pure endometrioid tumors; 659 had pure serous
      adenocarcinoma of the ovary. Response to platinum-based chemotherapy (PBC)
      overall survival, stage-for-stage median progression-free survival (PFS), and
      cause-specific median survival were compared. Independent predictors of survival
      were examined by using multivariate analyses. RESULTS: Median age of diagnosis
      for patients with endometrioid tumors was younger than those with serous
      adenocarcinoma of the ovary (60 years vs 62 years; P = .013). They presented more
      often with early disease (stage I and II; 50% vs 17%; P < .001), had less
      ascites, and had better performance status both overall and for stage II and III
      disease. More endometrioid tumors were optimally debulked overall (71% vs 45%; P
      < .001), but there was no difference according to stage. Objective and CA125 PBC
      response rates were not significantly different, but median PFS was better for
      patients with endometrioid tumors (24 months vs 13 months; P < .0001) as was
      overall median survival (48 months vs 22 months; P < .0001). This relation
      remained for stage II and III disease and for moderately and poorly
      differentiated tumors. Patients with concurrent endometrioid ovarian and
      endometrial malignancies had a survival advantage compared with those with
      ovarian malignancies alone. Independent predictors of survival after PBC were
      histological type, debulking status, and disease stage. CONCLUSIONS: Despite
      similar PBC response rates, endometrioid histology is associated with better
      survival compared with serous adenocarcinoma of the ovary, even with stage III or
      poorly differentiated tumors.

PMID- 18344212
TI  - Acute toxicity and bioaccumulation of arsenic in freshwater clam Corbicula
      fluminea.
AB  - Arsenic is a potent human carcinogen of skin, lung, and urinary bladder.
      Freshwater clam Corbicula fluminea is a commercially important native species in
      Taiwan. C. fluminea is also a suitable biomonitoring test organism. Little is
      known, however, about the actual effects of arsenic on C. fluminea. The
      objectives of this study were to provide information on the acute toxicity and
      bioaccumulation kinetics of arsenic in C. fluminea. We carried out a 14-day
      exposure experiment to obtain bioaccumulation parameters. Uptake was very rapid
      when C. fluminea was first exposed and then slightly decayed during the uptake
      phase of the experiment and an uptake rate constant of 1.718 +/- 6.70 (mean +/-
      SE) mL g(-1) d(-1) was estimated. The elimination of arsenic from C. fluminea
      obeyed first-order depuration kinetics (r(2) = 0.85, p < 0.05) with a calculated
      half-life of 6.80 days. The derived bioaccumulation factor of 16.84 suggests that
      arsenic has a high potential for bioaccumulation in C. fluminea. This had
      important implications for dietary exposure of arsenic to humans who eat
      contaminated clams, because the soft tissue usually constitutes the majority of
      tissue consumed. The 96-h LC50 value was estimated to be 20.74 (95% CI: 11.74
      30.79) mg L(-1) obtained from a 7-day acute toxicity bioassay. We also
      kinetically linked an acute toxicity model and a Hill sigmoid model to
      reconstruct an internal effect concentration based dose-response profile to
      assess the effect of soft tissue arsenic burden on the C. fluminea mortality.
      This result could be used to support the establishment of an ecological risk
      assessment to prevent possible ecosystem and human health consequences.

PMID- 18344213
TI  - Application of a new bioassay technique using goldfish for assessment of water
      toxicity.
AB  - There are a variety of chemicals in aquatic environment, so it is important to
      assess the toxicity. The biomarkers such as induction of DNA damage, micronuclei,
      vitellogenin, and hepatic P450 in fish are known to be effective for monitoring
      genotoxic and/or estrogenic chemicals. However, there is little study to use
      these biomarkers in same fish. Goldfish (Carassius auratus) is widely used and is
      suitable in size to collect blood or organs. In this study, validity of multiple
      biomarkers in goldfish was checked using standard chemicals and applied in the
      river water. Ho River, which flows through the textile dyeing factory in Shizuoka
      Prefecture, Japan, was reported to show genotoxicity toward Salmonella
      typhimurium TA98 and YG1024. When the goldfish were exposed to Ho River, DNA
      damage, estrogenic activity, and CYP1A induction were observed. Through the
      study, it was assumed that not only mutagens/carcinogens but also endocrine
      disrupting chemicals and poly aromatic hydrocarbons were present in Ho River.
      Therefore, chemical identification should be required. We could evaluate both
      genotoxicity and estrogenic activity simultaneously, so goldfish might be a good
      experimental model for estimation of chemical contamination levels in aquatic
      environment.

PMID- 18344214
TI  - Validation of neural tube defects in the full featured--general practice research
      database.
AB  - BACKGROUND: The General Practice Research Database (GPRD) has been used to
      identify associations between pregnancy medication exposures and birth defects,
      but experts have argued that databases such as this one cannot provide detailed
      information for the valid identification of complicated congenital anomalies. Our
      objective was to determine if the GPRD could be used to identify cases of neural
      tube defects (NTDs). METHODS: First, we created algorithms for anencephaly,
      encephalocele, meningocele, and spina bifida and used them to identify potential
      cases. We used the algorithms to identify 217 potential NTD cases in either a
      child's or a mother's record. We validated cases by querying general
      practitioners (GPs) via questionnaire. Where cases of NTD were identified in the
      mother's record, in addition to confirming the diagnosis, we asked the GPs if the
      diagnosis was for the mother or that of her fetus or offspring. RESULTS: Two
      hundred seventeen cases were identified, and 165 GP questionnaires were returned.
      We validated an NTD diagnosis for 117 cases, giving our algorithms a positive
      predictive value (PPV) of 0.71. The PPVs varied by NTD type: 0.81 for
      anencephaly, 0.83 for cephalocele, 0.64 for meningocele, and 0.47 for spina
      bifida. CONCLUSIONS: Our identification algorithm was useful in identifying three
      of the four types of NTDs studied. Additional information is necessary to
      accurately identify cases of spina bifida.

PMID- 18344215
TI  - Hesperidin in orange juice reduces the absorption of celiprolol in rats.
AB  - It has been reported that the intestinal absorption of celiprolol, an
      antihypertensive drug, is inhibited when it is taken with orange juice; it has
      been suggested that element(s) in citrus juice are responsible for this. In the
      present study, the pharmacokinetic interaction between celiprolol and orange
      juice was characterized through in vivo experiments with rats. Celiprolol 5 mg/kg
      was injected into the rat duodenum together with 5 ml/kg of neutralized orange
      juice or the same concentration of hesperidin as in the orange juice. Plasma
      celiprolol concentrations were measured by liquid chromatography-electrospray
      ionization-mass spectrometry (LC-ESI-MS). Concomitant administration of orange
      juice or hesperidin with celiprolol significantly decreased the area under the
      plasma concentration-time curve (AUC) by 74% and 75%, respectively, compared with
      control. These findings suggest that hesperidin is responsible for the decreased
      absorption of celiprolol and that orange juice taken with celiprolol has an
      inhibiting effect on intestinal absorption of the drug.

PMID- 18344216
TI  - Constrained dansyl derivatives reveal bacterial specificity of highly conserved
      thymidylate synthases.
AB  - The elucidation of the structural/functional specificities of highly conserved
      enzymes remains a challenging area of investigation, and enzymes involved in
      cellular replication are important targets for functional studies and drug
      discovery. Thymidylate synthase (TS, ThyA) governs the synthesis of thymidylate
      for use in DNA synthesis. The present study focused on Lactobacillus casei TS
      (LcTS) and Escherichia coli TS (EcTS), which exhibit 50 % sequence identity and
      strong folding similarity. We have successfully designed and validated a chemical
      model in which linear, but not constrained, dansyl derivatives specifically
      complement the LcTS active site. Conversely, chemically constrained dansyl
      derivatives showed up to 1000-fold improved affinity for EcTS relative to the
      inhibitory activity of linear derivatives. This study demonstrates that the
      accurate design of small ligands can uncover functional features of highly
      conserved enzymes.

PMID- 18344219
TI  - An experimental study of hybridizing cultural algorithms and local search.
AB  - In this paper the performance of the Cultural Algorithms-Iterated Local Search
      (CA-ILS), a new continuous optimization algorithm, is empirically studied on
      multimodal test functions proposed in the Special Session on Real-Parameter
      Optimization of the 2005 Congress on Evolutionary Computation. It is compared
      with state-of-the-art methods attending the Session to find out whether the
      algorithm is effective in solving difficult problems. The test results show that
      CA-ILS may be a competitive method, at least in the tested problems. The results
      also reveal the classes of problems where CA-ILS can work well and/or not well.

PMID- 18344220
TI  - Tabu search model selection for SVM.
AB  - A model selection method based on tabu search is proposed to build support vector
      machines (binary decision functions) of reduced complexity and efficient
      generalization. The aim is to build a fast and efficient support vector machines
      classifier. A criterion is defined to evaluate the decision function quality
      which blends recognition rate and the complexity of a binary decision functions
      together. The selection of the simplification level by vector quantization, of a
      feature subset and of support vector machines hyperparameters are performed by
      tabu search method to optimize the defined decision function quality criterion in
      order to find a good sub-optimal model on tractable times.

PMID- 18344221
TI  - Patterns out of cases using kohonen maps in breast cancer diagnosis.
AB  - DESMAI is a framework for helping experts in breast cancer diagnosis. It allows
      experts to explore digital mammographic image databases according to a certain
      topology criteria when they need to decide whether a sample is benign or
      malignant. In this way, they are provided with complementary information to
      enhance their interpretations and predictions. The core of the application is a
      SOMCBR system, which is variant of a Case-Based Reasoning system featured by
      organizing the case memory using a Self-Organizing Map. The article presents a
      strategy for improving the SOMCBR reliability thanks to the relations between
      cases and clusters. The approach is successfully applied in DESMAI for
      estimating, if it is possible, the class of the recovered mammographies.

PMID- 18344222
TI  - Towards expanding relevance vector machines to large scale datasets.
AB  - In this paper we develop and analyze methods for expanding automated learning of
      Relevance Vector Machines (RVM) to large scale text sets. RVM rely on Bayesian
      inference learning and while maintaining state-of-the-art performance, offer
      sparse and probabilistic solutions. However, efforts towards applying RVM to
      large scale sets have met with limited success in the past, due to computational
      constraints. We propose a diversified set of divide-and-conquer approaches where
      decomposition techniques promote the definition of smaller working sets that
      permit the use of all training examples. The rationale is that by exploring
      incremental, ensemble and boosting strategies, it is possible to improve
      classification performance, taking advantage of the large training set available.
      Results on Reuters-21578 and RCV1 are presented, showing performance gains and
      maintaining sparse solutions that can be deployed in distributed environments.

PMID- 18344223
TI  - Two-stage biometric authentication method using thought activity brain waves.
AB  - Brain waves are proposed as a biometric for verification of the identities of
      individuals in a small group. The approach is based on a novel two-stage
      biometric authentication method that minimizes both false accept error (FAE) and
      false reject error (FRE). These brain waves (or electroencephalogram (EEG)
      signals) are recorded while the user performs either one or several thought
      activities. As different individuals have different thought processes, this idea
      would be appropriate for individual authentication. In this study, autoregressive
      coefficients, channel spectral powers, inter-hemispheric channel spectral power
      differences, inter-hemispheric channel linear complexity and non-linear
      complexity (approximate entropy) values were used as EEG features by the two
      stage authentication method with a modified four fold cross validation procedure.
      The results indicated that perfect accuracy was obtained, i.e. the FRE and FAE
      were both zero when the proposed method was tested on five subjects using certain
      thought activities. This initial study has shown that the combination of the two
      stage authentication method with EEG features from thought activities has good
      potential as a biometric as it is highly resistant to fraud. However, this is
      only a pilot type of study and further extensive research with more subjects
      would be necessary to establish the suitability of the proposed method for
      biometric applications.

PMID- 18344224
TI  - Who needs A current? Functional remodelling in the Kv4.2-/- mouse.

PMID- 18344225
TI  - Bend those knees!

PMID- 18344226
TI  - The control of motoneurone activity: getting all of the players on the same
      stage.

PMID- 18344227
TI  - New directions in synaptic and network plasticity--a move away from NMDA receptor
      mediated plasticity.

PMID- 18344228
TI  - The mechanism selecting the guide strand from small RNA duplexes is different
      among argonaute proteins.
AB  - Double-stranded RNA induces RNA silencing and is cleaved into 21-24 nt small RNA
      duplexes by Dicer enzyme. A strand of Dicer-generated small RNA duplex (called
      the guide strand) is then selected by a thermodynamic mechanism to associate with
      Argonaute (AGO) protein. This AGO-small RNA complex functions to cleave mRNA,
      repress translation or modify chromatin structure in a sequence-specific manner.
      Although a model plant, Arabidopsis thaliana, contains 10 AGO genes, their roles
      and molecular mechanisms remain obscure. In this study, we analyzed the roles of
      Arabidopsis AGO2 and AGO5. Interestingly, the 5' nucleotide of small RNAs that
      associated with AGO2 was mainly adenine (85.7%) and that with AGO5 was mainly
      cytosine (83.5%). Small RNAs that were abundantly cloned from the AGO2
      immunoprecipitation fraction (miR163-LL, which is derived from the Lower Left of
      mature miR163 in pre-miR163, and miR390) and from the AGO5 immunoprecipitation
      fraction (miR163-UL, which is derived from the Upper Left of mature miR163 in pre
      miR163, and miR390(*)) are derived from the single small RNA duplexes, miR163
      LL/miR163-UL and miR390/miR390(*). Each strand of the miR163-LL/miR163-UL duplex
      is selectively sorted to associate with AGO2 or AGO5 in a 5' nucleotide-dependent
      manner rather than in a thermodynamic stability-dependent manner. Furthermore, we
      showed that both AGO2 and AGO5 have the ability to bind cucumber mosaic virus
      derived small RNAs. These results clearly indicate that the mechanism selecting
      the guide strand is different among AGO proteins and that multiple AGO genes are
      involved in anti-virus defense in plants.

PMID- 18344229
TI  - A protocol improves GP recording of long-term sickness absence risk factors.
AB  - BACKGROUND: If general practitioners (GPs) were better informed about patients'
      risks of long-term sickness absence (LTSA), they could incorporate these risk
      assessments into their patient management plans and cooperate more with
      occupational physicians to prevent LTSA. AIM: To evaluate the effectiveness of a
      protocol helping GPs in recording risks of LTSA and in co-operating with
      occupational physicians (OPs). METHODS: Twenty-six GPs (co-operating in four
      groups) in Amsterdam, The Netherlands, participated in a controlled intervention
      study. Fourteen GPs were the protocol-supported intervention group and twelve GPs
      were the reference group. Outcome measures were consultations containing work
      related information, information about two risk factors for LTSA, referrals to
      OPs and contacts of OPs with GPs and patients. Outcomes were identified through
      an electronic search in the GPs' information systems. Entries containing
      information were independently scored by two investigators. The proportions of
      patients with consultations documenting LTSA-pertinent items were compared
      between the groups, accounting for differences at baseline. RESULTS: There was no
      increase in consultations containing work-related information. Recording of risk
      factor information increased in the intervention group; the difference was 4.5%
      [95% CI 1.5-7.6] and 1.8% (95% CI -0.8 to 4.4) for the two risk factors. The
      referral rate to the OP increased by 2.9% (95% CI 1.2-4.5). There was no effect
      on contacts of OPs with GPs or with patients. CONCLUSION: Protocol-supported
      consultations may lead to a modest increase in information regarding two risk
      factors for LTSA in GPs' electronic records and to more referrals to OPs.

PMID- 18344230
TI  - Predicting changes in physical activity among adolescents: the role of self
      efficacy, intention, action planning and coping planning.
AB  - This paper aims to test the direct predictors of the theory of planned behaviour
      (TPB), action planning and coping planning as predictors of changes in physical
      activity (PA) in 157 adolescents (mean age: 12). TPB measures, the Action
      Planning and Coping Planning Scales (APCPS) and the International Physical
      Activity Questionnaires were measured at baseline, 2- and 5-month follow-up.
      Hierarchical regression analyses were conducted regressing PA at Time 2 or Time 3
      onto TPB and APCPS at baseline or Time 2, respectively. Past behaviour accounted
      for a significant 25-51% of the variance in PA in Step 1 of all three analyses.
      In Step 2, TPB accounted for an additional 3-10% with intention as a significant
      predictor. While no main effects for action planning or coping planning (Step 3)
      were found, all three analyses resulted in a significant amount of incremental
      variance accounted for by the interaction of action planning and coping planning
      (Step 4). Results suggest that the combination of high levels of action planning
      and coping planning is associated with increases in PA. Implications for theory
      of behaviour change in adolescents are discussed.

PMID- 18344231
TI  - The in vivo phosphorylation sites in multiple isoforms of amphiphysin I from rat
      brain nerve terminals.
AB  - Amphiphysin I (amphI) is dephosphorylated by calcineurin during nerve terminal
      depolarization and synaptic vesicle endocytosis (SVE). Some amphI phosphorylation
      sites (phosphosites) have been identified with in vitro studies or
      phosphoproteomics screens. We used a multifaceted strategy including 32P tracking
      to identify all in vivo amphI phosphosites and determine their relative abundance
      and potential relevance to SVE. AmphI was extracted from 32P-labeled
      synaptosomes, phosphopeptides were isolated from proteolytic digests using TiO2
      chromatography, and mass spectrometry revealed 13 sites: serines 250, 252, 262,
      268, 272, 276, 285, 293, 496, 514, 539, and 626 and Thr-310. These were
      distributed into two clusters around the proline-rich domain and the C-terminal
      Src homology 3 domain. Hierarchical phosphorylation of Ser-262 preceded
      phosphorylation of Ser-268, -272, -276, and -285. Off-line HPLC separation and
      two-dimensional tryptic mapping of 32P-labeled amphI revealed that Thr-310, Ser
      293, Ser-285, Ser-272, Ser-276, and Ser-268 contained the highest 32P
      incorporation and were the most stimulus-sensitive. Individually Thr-310 and Ser
      293 were the most abundant phosphosites, incorporating 16 and 23% of the 32P. The
      multiple phosphopeptides containing Ser-268, Ser-276, Ser-272, and Ser-285 had
      27% of the 32P. Evidence for a role for at least one proline-directed protein
      kinase and one non-proline-directed kinase was obtained. Four phosphosites
      predicted for non-proline-directed kinases, Ser-626, -250, -252, and -539,
      contained low amounts of 32P and were not depolarization-responsive. At least one
      alternatively spliced amphI isoform was identified in synaptosomes as being
      constitutively phosphorylated because it did not incorporate 32P during the 1-h
      labeling period. Multiple phosphosites from amphI-co-migrating synaptosomal
      proteins were also identified, including SGIP (Src homology 3 domain growth
      factor receptor-bound 2 (Grb2)-like (endophilin)-interacting protein 1), AAK1,
      eps15R, MAP6, alpha/beta-adducin, and HCN1. The results reveal two sets of amphI
      phosphosites that are either dynamically turning over or constitutively
      phosphorylated in nerve terminals and improve understanding of the role of
      individual amphI sites or phosphosite clusters in synaptic SVE.

PMID- 18344232
TI  - Quantitative and temporal proteome analysis of butyrate-treated colorectal cancer
      cells.
AB  - Colorectal cancer is one of the most common cancers in developed countries, and
      its incidence is negatively associated with high dietary fiber intake. Butyrate,
      a short-chain fatty acid fermentation by-product of fiber induces cell maturation
      with the promotion of growth arrest, differentiation, and/or apoptosis of cancer
      cells. The stimulation of cell maturation by butyrate in colonic cancer cells
      follows a temporal progression from the early phase of growth arrest to the
      activation of apoptotic cascades. Previously we performed two-dimensional DIGE to
      identify differentially expressed proteins induced by 24-h butyrate treatment of
      HCT-116 colorectal cancer cells. Herein we used quantitative proteomics
      approaches using iTRAQ (isobaric tags for relative and absolute quantitation), a
      stable isotope labeling methodology that enables multiplexing of four samples,
      for a temporal study of HCT-116 cells treated with butyrate. In addition,
      cleavable ICAT, which selectively tags cysteine-containing proteins, was also
      used, and the results complemented those obtained from the iTRAQ strategy.
      Selected protein targets were validated by real time PCR and Western blotting. A
      model is proposed to illustrate our findings from this temporal analysis of the
      butyrate-responsive proteome that uncovered several integrated cellular processes
      and pathways involved in growth arrest, apoptosis, and metastasis. These
      signature clusters of butyrate-regulated pathways are potential targets for novel
      chemopreventive and therapeutic drugs for treatment of colorectal cancer.

PMID- 18344233
TI  - Deep coverage mouse red blood cell proteome: a first comparison with the human
      red blood cell.
AB  - Mice have close genetic/physiological relationships to humans, breed rapidly, and
      can be genetically modified, making them the most used mammal in biomedical
      research. Because the red blood cell (RBC) is the sole gas transporter in
      vertebrates, diseases of the RBC are frequently severe; much research has
      therefore focused on RBC and cardiovascular disorders of mouse and humans. RBCs
      also host malaria parasites. Recently we presented an in-depth proteome for the
      human RBC. Here we present directly comparable data for the mouse RBC as membrane
      only, soluble-only, and combined membrane-bound/soluble proteomes (comprising,
      respectively, 247, 232, and 165 proteins). All proteins were identified,
      validated, and categorized in terms of subcellular localization, protein family,
      and function, and in comparison with the human RBC, were classified as orthologs,
      family-related, or unique. Splice isoforms were identified, and polypeptides
      migrating with anomalous apparent molecular weights were grouped into putatively
      ubiquitinated or partially degraded complexes. Overall there was close
      concordance between mouse and human proteomes, confirming the unexpected RBC
      complexity. Several novel findings in the human proteome have been confirmed
      here. This comparison sheds light on several open issues in RBC biology and
      provides a departure point for more comprehensive understanding of RBC function.

PMID- 18344234
TI  - Septic arthritis in a native joint due to Anaerococcus prevotii.
AB  - A 37-year-old injecting drug user presented with signs and symptoms of septic
      arthritis. Staphylococcus aureus was grown from his blood cultures. Despite
      treatment with flucloxacillin and fusidic acid his condition continued to
      deteriorate. Echocardiography showed no signs of endocarditis. Culture of his
      knee aspirate grew Anaerococcus prevotii after 5 days of incubation.
      Metronidazole was added to his treatment regime. A collection of pus (800 ml) was
      drained from the right thigh and A prevotii was isolated. His condition improved
      gradually and he was subsequently transferred to a drug rehabilitation unit after
      completing his antibiotic course. The importance of anaerobic streptococci in
      septic arthritis, as a very rare cause, is highlighted.

PMID- 18344235
TI  - Amelogenin positive cells scattered in the interstitial component of odontogenic
      fibromas.
AB  - BACKGROUND: Odontogenic tumours are often biphasic, consisting of epithelial and
      interstitial components, with an origin that is not well understood. Odontogenic
      fibromas are rich in mesenchymal component, but also have many epithelial nests.
      AIMS: To investigate the origin of this tumour by immunohistochemistry. METHODS:
      The expression of several odontogenic and epithelial markers, including
      amelogenin, was investigated by immunofluorescent studies. RESULTS:
      Immunohistochemical analysis showed that epithelial nests exhibited E-cadherin
      expression, but not amelogenin. Amelogenin positive cells were scattered in the
      fibrous tissue, which did not exhibit epithelial marker expression except for
      epithelial membrane antigen. In one case that had received a test biopsy before
      whole resection of tumour, amelogenin positive cells were distributed in the
      regenerating mucosal epithelium or subepithelial tissue. CONCLUSIONS: Results
      indicate that amelogenin positive cells of odontogenic fibromas have an
      epithelial origin and may have the potential for epithelial mesenchymal
      transition, which has not to date been investigated in benign tumours.

PMID- 18344236
TI  - The practical examination in chemical pathology: current role and future
      prospects.

PMID- 18344237
TI  - Hyperkalaemia as a complication of ureteroileostomy: a case report and literature
      review.

PMID- 18344238
TI  - Residual renal function: the delicate balance between benefits and risks.

PMID- 18344239
TI  - Evolution of large-vessel arteriopathy in paediatric patients with chronic kidney
      disease.
AB  - This observational study was designed to verify the hypothesis that the treatment
      modality significantly affects the evolution of CKD-associated arteriopathy.
      PATIENTS: Paediatric patients (mean age 13.8 +/- 4.2 years) with chronic kidney
      disease (CKD) stages 3-5, including 24 patients with mean GFR 54 +/- 21
      ml/min/1.73 m(2) (CKD group) and 32 patients in end-stage renal disease, of whom
      19 received a renal allograft (D-Rtx) and 13 remained on dialysis (D-D). METHODS:
      Sonography of the common carotid artery was performed at baseline and after 12
      months. Intima-media thickness (IMT) and the cross-sectional areas of the vessel
      wall (WCSA) and lumen (LCSA) were measured and normalized to age (SDS). RESULTS:
      At baseline IMT-SDS and WCSA-SDS were increased above normal, and were
      significantly higher in D than in CKD patients (P < 0.001). IMT-SDS increased
      over time in CKD and D-D patients (1.4 +/- 1.7 to 2.1 +/- 1.2, P = 0.05). In
      contrast, IMT-SDS (2.8 +/- 0.6 to 2.0 +/- 0.6, P < 0.005) decreased in those D
      Rtx patients who had elevated values prior to transplantation. The total number
      of patients with elevated cIMT-SDS changed from 7 to 13 in the 24 CKD, from 8 to
      11 in the 13 D-D and from 11 to 12 in the 19 D-Rtx patients. While IMT-SDS was
      independently correlated with blood pressure and serum phosphate in the CKD and D
      patients, only total dialysis vintage (r = 0.50; P < 0.05) and the IMT-SDS
      attained at the time of grafting (r = 0.46, P < 0.05) correlated with IMT-SDS 1
      year post-Rtx. CONCLUSION: While vascular lesions rapidly progress in CKD and D
      patients, abolition of the uraemic state by Rtx leads to stabilization or partial
      regression of CKD-associated arteriopathy. Cumulative dialysis duration and the
      degree of arterial damage prevalent at the time of grafting are the main
      determinants of persistent arteriopathy 1 year after Rtx.

PMID- 18344240
TI  - A 3D rotary renal and mesenchymal stem cell culture model unveils cell death
      mechanisms induced by matrix deficiency and low shear stress.
AB  - BACKGROUND: In epithelial and endothelial cells, detachment from the matrix
      results in anoikis, a form of apoptosis, whereas stromal and cancer cells are
      often anchorage independent. The classical anoikis model is based on static 3D
      epithelial cell culture conditions (STCK). METHODS: We characterized a new model
      of renal, stromal and mesenchymal stem cell (MSC) matrix deprivation, based on
      slow rotation cell culture conditions (ROCK). This model induces anoikis using a
      low shear stress, laminar flow. The mechanism of cell death was determined via
      FACS (fluorescence-activated cell sorting) analysis for annexin V and propidium
      iodide uptake and via DNA laddering. RESULTS: While only renal epithelial cells
      progressively died in STCK, the ROCK model could induce apoptosis in stromal and
      transformed cells; cell survival decreased in ROCK versus STCK to 40%, 52%, 62%
      and 7% in human fibroblast, rat MSC, renal cell carcinoma (RCC) and human
      melanoma cell lines, respectively. Furthermore, while ROCK induced primarily
      apoptosis in renal epithelial cells, necrosis was more prevalent in transformed
      and cancer cells [necrosis/apoptosis ratio of 72.7% in CaKi-1 RCC cells versus
      4.3% in MDCK (Madin-Darby canine kidney) cells]. The ROCK-mediated shift to
      necrosis in RCC cells was further accentuated 3.4-fold by H(2)O(2)-mediated
      oxidative stress while in adherent HK-2 renal epithelial cells, oxidative stress
      enhanced apoptosis. ROCK conditions could also unveil a similar pattern in the
      LZ100 rat MSC line where in ROCK 44% less apoptosis was observed versus STCK and
      45% less apoptosis versus monolayer conditions. Apoptosis in response to
      oxidative stress was also attenuated in the rat MSC line in ROCK, thereby
      highlighting rat MSC transformation. CONCLUSIONS: The ROCK matrix-deficiency cell
      culture model may provide a valuable insight into the mechanism of renal and MSC
      cell death in response to matrix deprivation.

PMID- 18344241
TI  - Advanced glycation end-products induce cell cycle arrest and hypertrophy in
      podocytes.
AB  - BACKGROUND: Podocyte injury with loss of cells into the urine seems to be an
      early factor in diabetic nephropathy. Advanced glycation end-products (AGEs) are
      important mediators of structural and functional renal abnormalities in diabetic
      nephropathy. We and others have previously described that mice with a deletion in
      the gene for the cell cycle regulatory p27(Kip1) are protected from some features
      of diabetic nephropathy. METHODS: The present study investigates a potential
      influence of AGE-modified bovine serum albumin (AGE-BSA) on podocyte growth and
      p27(Kip1) expression in culture. The p27(Kip1) expression was measured by western
      blots and real-time PCR. Cell cycle analysis, cell hypertrophy, proliferation and
      various markers of apoptosis and necrosis were assessed. The p27(Kip) expression
      was inhibited by siRNA or was overexpressed in podocytes with an inducible
      expression system. RESULTS: AGE-BSA was actively taken up into the cell as
      determined by immunohistochemistry, western blots and HPLC. Incubation with AGE
      BSA induced in differentiated podocytes, but not in tubular cells, p27(Kip1) mRNA
      and protein expression. This induction was associated with cell cycle arrest of
      podocytes, cell hypertrophy (as measured by increases in cell size and
      protein/cell number ratios) and an increase in necrotic, but not apoptotic cells.
      Inhibition of p27(Kip1) expression with siRNA halted the AGE-BSA-mediated cell
      cycle arrest and hypertrophy, but did not interfere with AGE uptake into
      podocytes. In contrast, overexpression of p27(Kip1) using an inducible expression
      system stimulated hypertrophy and cell cycle arrest of podocytes. CONCLUSION: Our
      data demonstrate that AGE-BSA-induced hypertrophy and damage of cultured
      podocytes occurs by a mechanism involving p27(Kip1). This effect can contribute
      to the loss of podocytes in diabetic nephropathy.

PMID- 18344242
TI  - Why less success of the peritoneal dialysis programmes in Europe?

PMID- 18344243
TI  - Absence of vascular remodelling in a high angiotensin-II state (Bartter's and
      Gitelman's syndromes): implications for angiotensin II signalling pathways.
AB  - BACKGROUND: Angiotensin II (Ang II) is a powerful proinflammatory cytokine and
      growth factor that activates NF-kappaB, as well as NAD(P)H oxidase, and thus is a
      key factor for the induction and progression of cardiovascular diseases. Our
      previous studies have shown high Ang II and high blood pressure-driven
      proatherogenic remodelling in an animal model. To further explore Ang II in
      proatherogenic vascular remodelling independent of blood pressure, we used
      Bartter's/Gitelman's syndrome (BS/GS) patients given their elevated plasma Ang
      II, yet normo/hypotension, because extensive mechanistic studies in these
      patients suggest they are a good model to explore Ang II-mediated signalling.
      METHODS: The study evaluated BS/GS patients for nitric oxide-dependent (FMD) and 
      independent vasodilation and intima-media thickness (IMT) of the carotid arteries
      compared with healthy subjects and essential hypertensive patients. RESULTS: The
      results showed the absence of IMT growth in BS/GS patients as cumulative mean-IMT
      and mean maximum-IMT levels in BS/GS did not differ from normotensives: 0.58 +/-
      0.09 mm versus 0.60 +/- 0.09 and 0.67 +/- 0.09 versus 0.70 +/- 0.13 respectively,
      P = ns, but were significantly lower compared with hypertensive patients: 0.69 +/
      0.13, P < 0.046 and 0.85 +/- 0.19, P < 0.018, respectively. FMD was increased in
      BS/GS versus hypertensives or normotensive controls (10.8 +/- 2.7% versus 6.5 +/-
      2.3 and 8.7 +/- 1.9, P < 0.002 respectively) while endothelium-independent
      dilation did not differ (10.2 +/- 3.6% versus 7.2 +/- 1.9 and 8.2 +/- 3.3, P =
      ns) between groups. CONCLUSIONS: Our study in BS/GS provides to our knowledge the
      first clinical data that point to a direct proatherogenic role for Ang II.
      However, because the data are derived from findings in BS/GS and therefore are
      indirect, further studies in this and other models using more direct approaches
      should be pursued to demonstrate a direct proatherogenic effect of Ang II as well
      as further studies on Ang II type 2 receptor (AT2R) signalling that the spectrum
      of findings of this and other studies indicate as involved in the lack of
      vascular remodelling.

PMID- 18344244
TI  - Serum cystatin C performs similarly to traditional markers of kidney function in
      the evaluation of donor kidney function prior to and following unilateral
      nephrectomy.
AB  - Background and objectives. It is essential that candidates for kidney donation be
      carefully screened to ensure safety of donation and monitored following
      unilateral nephrectomy as previous experience has demonstrated loss of kidney
      function of up to 50% following donation. The low-molecular-weight protein
      cystatin C (cysC) has been introduced as an alternative to serum creatinine for
      estimation of glomerular filtration rate (GFR). In particular, serum cysC is
      sensitive to detect mild GFR reduction between 60 and 90 ml/min/1.73 m(2) that
      would make it a potentially effective screening and monitoring test in live
      kidney donors. Design, setting, participants and measurements. We examined the
      utility of cysC as compared to other traditional measures of kidney function,
      including serum creatinine and 24-h urine for creatinine clearance, in the
      evaluation of kidney function in 51 consecutive live kidney donors both prior to
      and following unilateral nephrectomy. RESULTS: This is the largest experience
      reported in the living kidney donor population. We found that living kidney
      donors at our centre lost approximately 30-35% of kidney function following
      unilateral nephrectomy and this remained stable >1 year. Furthermore, we observed
      that cysC correlated well with all other markers of kidney function and detected
      acute changes in kidney function immediately post-nephrectomy. CONCLUSIONS:
      Overall, however, cysC did not confer any advantage with respect to preoperative
      assessment of kidney function or for monitoring following live kidney donation as
      compared to more traditional measures.

PMID- 18344245
TI  - Continuous deep sedation for patients nearing death in the Netherlands:
      descriptive study.
AB  - OBJECTIVES: To study the practice of continuous deep sedation in 2005 in the
      Netherlands and compare it with findings from 2001. DESIGN: Questionnaire study
      about random samples of deaths reported to a central death registry in 2005 and
      2001. SETTING: Nationwide physician study in the Netherlands. PARTICIPANTS:
      Reporting physicians received a questionnaire about the medical decisions that
      preceded the patient's death; 78% (n=6860) responded in 2005 and 74% (n=5617) in
      2001. MAIN OUTCOME MEASURES: Characteristics of continuous deep sedation
      (attending physician, types of patients, drugs used, duration, estimated effect
      on shortening life, palliative consultation). Requests for euthanasia. RESULTS:
      The use of continuous deep sedation increased from 5.6% (95% confidence interval
      5.0% to 6.2%) of deaths in 2001 to 7.1% (6.5% to 7.6%) in 2005, mostly in
      patients treated by general practitioners and in those with cancer (in 2005, 47%
      of sedated patients had cancer v 33% in 2001). In 83% of cases sedation was
      induced by benzodiazepines, and in 94% patients were sedated for periods of less
      than one week until death. Nine per cent of those who received continuous deep
      sedation had previously requested euthanasia but their requests were not granted.
      Nine per cent of the physicians had consulted a palliative expert. CONCLUSIONS:
      The increased use of continuous deep sedation for patients nearing death in the
      Netherlands and the limited use of palliative consultation suggests that this
      practice is increasingly considered as part of regular medical practice.

PMID- 18344246
TI  - Continuous deep sedation in patients nearing death.

PMID- 18344247
TI  - Biological sequence classification utilizing positive and unlabeled data.
AB  - MOTIVATION: In the genomics setting, an increasingly common data configuration
      consists of a small set of sequences possessing a targeted property (positive
      instances) amongst a large set of sequences for which class membership is unknown
      (unlabeled instances). Traditional two-class classification methods do not
      effectively handle such data. RESULTS: Here, we develop a novel method, likely
      positive-iterative classification (LP-IC) for this problem, and contrast its
      performance with the few existing methods, most of which were devised and
      utilized in the text classification context. LP-IC employs an iterative
      classification scheme and introduces a class dispersion measure, adopted from
      unsupervised clustering approaches, to monitor the model selection process. Using
      two case studies--prediction of HLA binding, and alternative splicing
      conservation between human and mouse--we show that LP-IC provides superior
      performance to existing methodologies in terms of: (i) combined accuracy and
      precision in positive identification from the unlabeled set; and (ii) predictive
      performance of the resultant classifiers on independent test data.

PMID- 18344248
TI  - Fitting a geometric graph to a protein-protein interaction network.
AB  - MOTIVATION: Finding a good network null model for protein-protein interaction
      (PPI) networks is a fundamental issue. Such a model would provide insights into
      the interplay between network structure and biological function as well as into
      evolution. Also, network (graph) models are used to guide biological experiments
      and discover new biological features. It has been proposed that geometric random
      graphs are a good model for PPI networks. In a geometric random graph, nodes
      correspond to uniformly randomly distributed points in a metric space and edges
      (links) exist between pairs of nodes for which the corresponding points in the
      metric space are close enough according to some distance norm. Computational
      experiments have revealed close matches between key topological properties of PPI
      networks and geometric random graph models. In this work, we push the comparison
      further by exploiting the fact that the geometric property can be tested for
      directly. To this end, we develop an algorithm that takes PPI interaction data
      and embeds proteins into a low-dimensional Euclidean space, under the premise
      that connectivity information corresponds to Euclidean proximity, as in geometric
      random graphs. We judge the sensitivity and specificity of the fit by computing
      the area under the Receiver Operator Characteristic (ROC) curve. The network
      embedding algorithm is based on multi-dimensional scaling, with the square root
      of the path length in a network playing the role of the Euclidean distance in the
      Euclidean space. The algorithm exploits sparsity for computational efficiency,
      and requires only a few sparse matrix multiplications, giving a complexity of
      O(N(2)) where N is the number of proteins. RESULTS: The algorithm has been
      verified in the sense that it successfully rediscovers the geometric structure in
      artificially constructed geometric networks, even when noise is added by re
      wiring some links. Applying the algorithm to 19 publicly available PPI networks
      of various organisms indicated that: (a) geometric effects are present and (b)
      two-dimensional Euclidean space is generally as effective as higher dimensional
      Euclidean space for explaining the connectivity. Testing on a high-confidence
      yeast data set produced a very strong indication of geometric structure (area
      under the ROC curve of 0.89), with this network being essentially
      indistinguishable from a noisy geometric network. Overall, the results add
      support to the hypothesis that PPI networks have a geometric structure.
      AVAILABILITY: MATLAB code implementing the algorithm is available upon request.

PMID- 18344249
TI  - Risk factors for anticoagulation-related bleeding complications.

PMID- 18344250
TI  - Buddhist psychology, psychotherapy and the brain: a critical introduction.
AB  - Buddhist psychology is increasingly informing psychotherapeutic practice in the
      western world. This article: (a) provides a general background to Buddhist
      tradition; (b) outlines the central tenets of Buddhist psychology, with
      particular emphasis on the practice of meditation; (c) provides an overview of
      research into the effects of Buddhist practice on the brain; (d) outlines the
      relationships between Buddhist psychology and existing forms of psychotherapy;
      (e) provides an overview of Buddhist approaches to specific psychiatric disorders
      and the psychological aspects of physical disorders; and (f) discusses the
      emergence of Buddhist psychotherapy in western societies and explores likely
      future developments. There is a need for further research into the
      neuroscientific correlates of Buddhist concepts of mind and the evidence-base for
      the use of specific techniques (e.g., meditation) in psychotherapeutic practice.

PMID- 18344251
TI  - Jinn, psychiatry and contested notions of misfortune among east London
      Bangladeshis.
AB  - This study examines understandings of misfortune among east London Bangladeshis,
      particularly with respect to the role of jinn spirits. It reports on the findings
      of ethnographic interviews among 40 members of this community. Appeal to jinn
      explanations is commonplace at times of psychological disturbance and unexplained
      physical symptoms. Resort to traditional healers is frequent. These explanations
      are contested by different groups in the community. The findings are examined
      within the context of a discourse on tradition and modernity with particular
      emphasis on Islam and modernity.

PMID- 18344252
TI  - Anxious bliss: a case study of dissociation in a Mexican nun.
AB  - This is a case study of Celeste, postulant in a Roman Catholic convent in Mexico
      who experienced frequent episodes of leaving her body to commune with God. During
      these experiences, Celeste felt immersed in an ;incredibly beautiful profound
      silence' where ;time and space were broken.' But as much as Celeste craved these
      experiences, they also alarmed her; she was acutely aware that they might be
      indicative of psychological or neurological dysfunction. This article chronicles
      Celeste's struggles to make sense of her experiences in light of competing
      explanatory models. Her ultimate resolution suggests intriguing new directions
      for transcultural psychiatric research.

PMID- 18344253
TI  - U.K. Clergy and people in mental distress: community and patterns of pastoral
      care.
AB  - Despite the advance of secularizing influences in many western societies,
      religion and faith-based organizations play a significant role in the lives of
      many individuals and communities. Despite this, little is known about what clergy
      do when faced with mental health problems among their communities. Based on an
      analysis of in-depth interviews with U.K. Christian, Muslim and Jewish clergy
      this article examines models of pastoral care provided within different faith
      groups. The provision of such care was generally influenced by religious
      tradition and beliefs, community integrity and mission. Implications of the
      findings for collaboration with pastoral care are discussed.

PMID- 18344254
TI  - Paraprofessional counselling within asylum seekers' groups in the Netherlands:
      transferring an approach for a non-western context to a European setting.
AB  - This article presents the application of a psychosocial care approach, which has
      been developed for and in a non-western context, within an asylum seekers'
      setting in the Netherlands. The project aimed to increase access to basic
      psychosocial care to a target population that experiences difficulties in
      entering mental healthcare services, by a group of trained peer asylum seekers
      and refugees. The development of an informal paraprofessional support system
      makes better use of existing resources, provides secondary benefits for the
      participants and helps to overcome the treatment gap between perceived needs and
      the formal mental healthcare system. The article describes the key components of
      such an approach, the Dutch context, the project implementation and finishes with
      a discussion on outcomes, strengths and weaknesses, risks and recommendations. In
      summary, we found this community approach to be applicable and relevant within an
      asylum seekers' centre, as it incorporates an additional easy-access level of
      psychosocial care and social agency, which seemed to empower participants and
      help prevent psychosocial problems from becoming more severe.

PMID- 18344255
TI  - Phenomenology of near-death experiences: a cross-cultural perspective.
AB  - Near-death experiences (NDEs) include a set of subjective experiences encountered
      by people who were close to death or were faced with life-threatening situations.
      Reports have suggested that the phenomenology of NDE might differ across
      cultures. This article is aimed at providing an updated phenomenological
      perspective by comparing NDEs in a cross-cultural context. We compared the
      various descriptions of NDEs from a phenomenological perspective. There were
      similarities between particular cultures, which differed from typical western
      European experiences. This article concludes that although there are common
      themes, there are also reported differences in NDEs. The variability across
      cultures is most likely to be due to our interpretation and verbalizing of such
      esoteric events through the filters of language, cultural experiences, religion,
      education and their influence on our belief systems either shedding influence as
      an individual variable or more often perhaps by their rich interplay between
      these factors.

PMID- 18344256
TI  - For patients undergoing coronary artery bypass grafting at higher risk of stroke
      is the single cross-clamp technique of benefit in reducing the incidence of
      stroke?
AB  - A best evidence topic in cardiac surgery was written according to a structured
      protocol. The question addressed was whether, for patients undergoing coronary
      artery bypass grafting at higher risk of stroke, the single cross-clamp (SC)
      technique is of benefit in reducing the incidence of stroke. Using the reported
      search 458 papers were identified. Six randomised controlled trials (RCTs), of
      which one was a duplicate publication, represented the best evidence on the
      subject. The author, journal, date and country of publication, patient group
      studied, study type, relevant outcomes, results and study comments and weaknesses
      were tabulated for these. We conclude that current best available evidence, from
      six RCTs randomising 490 patients, suggests that there is no benefit of SC
      technique over multiple cross-clamp (MC) technique in terms of reduction in the
      incidence of stroke (SC=2/206 vs. MC=7/284; P=ns) although there is some
      advantage of SC technique in causing less neuropsychological deficits and release
      of serum S-100 protein, a surrogate marker of cerebral injury.

PMID- 18344257
TI  - The action of nitric oxide to enhance cell survival in chick cardiomyocytes is
      mediated through a cGMP and ERK1/2 pathway while p38 mitogen-activated protein
      kinase-dependent pathways do not alter cell death.
AB  - The objective of this study was to determine whether the dual action of nitric
      oxide (NO) on cardiomyocyte cell viability is mediated through p38 mitogen
      activated protein kinase (MAPK)-induced cell death and extracellular signal
      regulated kinase (ERK1/2)-mediated cell survival pathways, and whether either of
      these is mediated through a cGMP-protein kinase G (PKG) pathway. Cell viability
      of embryonic chick cardiomyocytes was assessed by the MTT assay, which is based
      on the ability of viable cells to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyl tetrazolium bromide. The NO donor sodium nitroprusside (SNP) produced a
      significant (P < 0.01) concentration-dependent reduction in cell viability or
      increase in cell death. Sodium nitroprusside induced ERK1/2 phosphorylation, and
      the mitogen-activated protein kinase (MEK1/2) inhibitor PD 98059 significantly
      increased cell death. In contrast, SB202190, a relatively selective inhibitor of
      p38 MAPK, did not affect SNP-induced cell death. The cardioprotective effect of
      NO was prbably mediated in part via cGMP because 1H-[1,2,4]oxadiazolo[4,3
      a]quinoxalin-1-one, a selective inhibitor of NO-sensitive guanylyl cyclase,
      produced a significant enhancement of SNP-induced cell death. In contrast, the
      PKG inhibitor KT5823 did not affect cell viability. In summary, these data
      suggest that NO, via stimulation of soluble guanylyl cyclase, activates MEK1/2
      whose product, ERK1/2, protects against cell death. In contrast, SNP-induced p38
      MAPK activation does not modulate NO-induced cardiomyocyte cell death. Not all
      cGMP targets affect NO-induced cell death, since the PKG pathway does not enhance
      or suppress NO-induced cardiomyocyte cell death. Enhancement of the ERK1/2
      responses to NO may permit the beneficial effects of NO to predominate.

PMID- 18344258
TI  - Using Physiome standards to couple cellular functions for rat cardiac excitation
      contraction.
AB  - Scientific endeavour is reliant upon the extension and reuse of previous
      knowledge. The formalization of this process for computational modelling is
      facilitated by the use of accepted standards with which to describe and simulate
      models, ensuring consistency between the models and thus reducing the development
      and propagation of errors. CellML 1.1, an XML-based programming language, has
      been designed as a modelling standard which, by virtue of its import and grouping
      functions, facilitates model combination and reuse. Using CellML 1.1, we
      demonstrate the process of formalized model reuse by combining three separate
      models of rat cardiomyocyte function (an electrophysiology model, a model of
      cellular calcium dynamics and a mechanics model) which together make up the
      Pandit-Hinch-Niederer et al. cell model. Not only is this integrative model of
      rat electromechanics a useful tool for cardiac modelling but it is also an ideal
      framework with which to demonstrate both the power of model reuse and the
      challenges associated with this process. We highlight and classify a number of
      these issues associated with combining models and provide some suggested
      solutions.

PMID- 18344259
TI  - Pontomedullary transection attenuates central respiratory modulation of
      sympathetic discharge, heart rate and the baroreceptor reflex in the in situ rat
      preparation.
AB  - Previous studies have indicated a major role for the pons in the genesis of the
      respiratory pattern. The respiratory rhythm is coupled to the cardiovascular
      system to ensure optimal matching of minute ventilation and cardiac output. Since
      much of this coupling results from cross-talk between brainstem circuits, we have
      assessed the role of the pons in both the co-ordination of respiratory and
      cardiovascular efferent activities and the baroreceptor reflex efficacy. Using
      the arterially perfused in situ rat preparation, we recorded neural activities
      from the left phrenic nerve, central end of the vagus nerve, thoracic sympathetic
      chain (T8-T10) and heart rate. Respiratory sinus arrhythmia, respiratory
      modulation of sympathetic nerve activity (and Traube-Hering waves in arterial
      pressure) and postinspiratory discharges recorded from vagal efferents were
      eliminated after pontine transection. We also found that although the sympathetic
      arterial baroreflex remained intact, respiratory gating of the baroreceptor
      reflex (i.e. both bradycardia and sympathoinhibition) was abolished after pontine
      removal. We propose that neural activity of the pons is essential for
      physiological coupling of centrally generated respiratory and cardiovascular
      efferent activities.

PMID- 18344260
TI  - Double-sigmoid model for fitting fatigue profiles in mouse fast- and slow-twitch
      muscle.
AB  - We present a curve-fitting approach that permits quantitative comparisons of
      fatigue profiles obtained with different stimulation protocols in isolated slow
      twitch soleus and fast-twitch extensor digitorum longus (EDL) muscles of mice.
      Profiles from our usual stimulation protocol (125 Hz for 500 ms, evoked once
      every second for 100-300 s) could be fitted by single-term functions (sigmoids or
      exponentials) but not by a double exponential. A clearly superior fit, as
      confirmed by the Akaiki Information Criterion, was achieved using a double
      sigmoid function. Fitting accuracy was exceptional; mean square errors were
      typically <1% and r(2) > 0.9995. The first sigmoid (early fatigue) involved
      approximately 10% decline of isometric force to an intermediate plateau in both
      muscle types; the second sigmoid (late fatigue) involved a reduction of force to
      a final plateau, the decline being 83% of initial force in EDL and 63% of initial
      force in soleus. The maximal slope of each sigmoid was seven- to eightfold
      greater in EDL than in soleus. The general applicability of the model was tested
      by fitting profiles with a severe force loss arising from repeated tetanic
      stimulation evoked at different frequencies or rest periods, or with excitation
      via nerve terminals in soleus. Late fatigue, which was absent at 30 Hz, occurred
      earlier and to a greater extent at 125 than 50 Hz. The model captured small
      changes in rate of late fatigue for nerve terminal versus sarcolemmal
      stimulation. We conclude that a double-sigmoid expression is a useful and
      accurate model to characterize fatigue in isolated muscle preparations.

PMID- 18344261
TI  - Permeability measurements in an individually perfused capillary: the 'squid axon'
      of the microcirculation (1974).

PMID- 18344262
TI  - Changes in dead space can explain part of the reduction in gas exchange
      efficiency found, not necessarily linked to respiratory sinus arrhythmia.

PMID- 18344264
TI  - Case report: Radiofrequency ablation for the treatment of painful isolated wound
      recurrence after resection of gastric cancer.
AB  - A 75-year-old woman underwent radiofrequency (RF) ablation for the treatment of
      two painful disseminated tumours that appeared and rapidly became larger at the
      anterior abdominal wound 16 months after she had undergone surgery for gastric
      cancer. RF ablation was performed under CT-fluoroscopic guidance for both
      tumours, which measured 5 cm and 3 cm in maximum diameter. Pain was relieved
      immediately after RF ablation, and both tumours showed significant involution
      upon physical examination and CT studies. The patient is still alive 15 months
      after RF ablation, with no evidence of tumour recurrence.

PMID- 18344265
TI  - Case report: Lymphoma-related resolving paraneoplastic myelopathy with MRI
      correlation.
AB  - We present here a case of paraneoplastic myelopathy with significant cord
      abnormality documented on MRI. Following treatment of the patient's underlying
      haematological malignancy, there was marked improvement both symptomatically and
      on follow-up MR imaging. This has rarely been described in the literature in
      relation to lymphoma or with imaging correlation.

PMID- 18344266
TI  - Case report: Giant coronary aneurysm caused by Kawasaki disease: follow-up with
      echocardiography and multidetector CT angiography.
AB  - Giant coronary artery aneurysms caused by Kawasaki disease are not common;
      however, they are one of the most serious complications and can be fatal. Here,
      we describe a 5-year-old girl with Kawasaki disease who initially had normal
      coronary arteries. Despite intravenous immunoglobulin, she developed progressive
      giant coronary artery aneurysms. Echocardiography is a non-invasive tool for
      imaging the condition but it does have some limitations, whereas selective
      coronary angiography is the gold standard. However, multidetector CT may be a
      better non-invasive tool, alternate to invasive catheterized selective coronary
      angiography, in the long-term follow-up of patients with a giant coronary
      aneurysm.

PMID- 18344267
TI  - Case report: Solitary plasmacytoma of bone with oncogenic osteomalacia:
      recurrence of tumour confirmed by PET/CT. A case report with a review of the
      radiological literature.
AB  - We describe a case of oncogenic osteomalacia secondary to solitary plasmacytoma
      of the vertebral body of T3. The patient presented with symptoms of
      hypophosphataemia. Following the initial diagnosis, the lesion was surgically
      resected with good results, although several follow-up procedures, including bone
      grafting, were necessary to stabilize the thoracic spine. The lesion recurred
      almost 15 years after its initial resection, again presenting with
      hypophosphataemia and neurological symptoms suggestive of local tumour
      recurrence. A variety of radiological examinations were performed in an attempt
      to confirm and localize recurrent tumour, including bone scintigraphy,
      (111)indium octreotide scintigraphy, high-resolution CT and MRI of the thoracic
      spine, but these yielded only negative or equivocal results owing, in part, to
      the presence of extensive post-operative changes, and also to a difference in the
      MR signals of the recurrent and original tumours. Positron emission tomography
      (PET/CT) demonstrated a solitary focus of intense fluorodeoxyglucose uptake in
      the T3 vertebral body, enabling a definitive diagnosis of recurrent plasmacytoma.
      This case illustrates the diagnostic value of PET/CT in the setting of
      challenging post-operative changes in the surrounding tissue and in the
      appearance of the tumour itself. Relevant related imaging literature is also
      reviewed.

PMID- 18344268
TI  - Case report: Jejuno-jejunal invagination from metastatic renal cell carcinoma.
AB  - Jejuno-jejunal invagination caused by metastatic renal cell carcinoma is a rare
      entity in the literature. We report a case of metastatic renal cell carcinoma
      that led to jejuno-jejunal invagination, which was diagnosed by multidedector CT
      examination.

PMID- 18344269
TI  - Case report: A case of polypoid endometriosis: MR pathological correlation.
AB  - We report a case of polypoid endometriosis and correlate the MRI findings with
      the pathological findings. The polypoid endometriosis appeared as multiple
      polypoid masses protruding into the adjacent pelvic organs, including the uterus
      and rectum. The masses were found to show hyperintensity on T(2) weighted images,
      which was similar to the signal intensity of the uterine endometrium, reflecting
      the presence of abundant endometrial-type glands. The masses were also surrounded
      by hypointense rim-like structures on T(2) weighted images. These structures were
      confirmed by pathology to correspond with fibrous tissues arising from
      endometriosis. These features, together with an intense enhancement similar to
      the adjacent uterus, may be a diagnostic clue to this rare entity.

PMID- 18344270
TI  - Case report: Second primary small cell carcinoma of the trachea in a breast
      cancer survivor: a case report and literature review.
AB  - Small cell carcinoma of the trachea is a rare entity and only a few cases have
      been described, none as a second malignant neoplasm. This is the first report of
      a metachronous second primary of the trachea with small cell histology in a
      breast cancer survivor. A 25-year-old woman was diagnosed initially with an
      infiltrating ductal carcinoma of the breast, and was treated with modified
      radical mastectomy followed by adjuvant chemo-radiotherapy. 10 years later, she
      presented with breathlessness and central airway obstruction. Bronchoscopy
      revealed an intraluminal lesion in the proximal trachea, which was reported as
      small cell carcinoma on biopsy. There was no evidence of loco-regional recurrence
      of the previously treated breast cancer. Whole-body positron emission tomography
      did not show any distant metastases. As it was a small cell carcinoma, she was
      treated with concurrent chemo-radiotherapy and remains loco-regionally
      controlled. Decision-making in such instances should take into account prior
      treatment and needs to be individualized. There is a need for increased awareness
      amongst primary care physicians regarding second malignant neoplasms in the long
      term follow-up of breast cancer patients treated with radiation and
      chemotherapeutic agents that have carcinogenic potential.

PMID- 18344271
TI  - Vertebrobasilar dolichoectasia: a rare cause of obstructive hydrocephalus: case
      report.
AB  - Here, we describe neuroimaging findings of an unusual case of severe
      vertebrobasilar dolichoectasia producing obstructive hydrocephalus. CT and MRI
      performed in a 71-year-old woman presenting with clinical features of raised
      intracranial pressure revealed severely ectatic and tortuous vertebral and
      basilar arteries. The ectatic basilar artery was causing compression and
      flattening of the midbrain. This had resulted in aqueductal compression and
      consequent obstructive hydrocephalus. The patient underwent emergency ventricular
      drainage, with resulting decompression of the ventricles and resolution of
      symptoms. Vertebrobasilar dolichoectasia refers to a markedly dilated and
      tortuous vertebrobasilar arterial system, occasionally presenting with
      thomboembolic episodes or symptoms related to local compressive effects, such as
      cranial nerve palsies. Direct midbrain compression with obstructive hydrocephalus
      is a rare complication that mandates emergency ventricular decompression.

PMID- 18344272
TI  - Multilocular thymic tuberculosis: case report.
AB  - Tuberculosis is a widely prevalent disease in India. However, primary thymic
      involvement is an extremely uncommon presentation of this entity; a review of the
      literature revealed only seven documented cases of primary thymic tuberculosis.
      With the increasing prevalence of human immunodeficiency virus (HIV) in India,
      however, the occurrence of tuberculosis in previously uncommon anatomical
      locations may become more frequent. We report the unusual clinical, radiological
      and pathological findings in a HIV seronegative 30-year-old Indian man with
      primary multilocular thymic tuberculosis.

PMID- 18344273
TI  - Imaging the heart valves using ECG-gated 64-detector row cardiac CT.
AB  - Multi-detector row cardiac CT imaging demonstrates clinical usefulness in
      valvular heart disease, for which CT has not been traditionally used.
      Electrocardiographic (ECG)-gated CT coronary angiography also has an established
      clinical role with an increasingly solid evidence base, and the same data set in
      these patients also provides valuable information about chamber and valvular
      structure and function; this information should also be considered when
      interpreting cardiac CT and non-ECG gated thoracic imaging. Although true flow
      data cannot be achieved using CT, as with echocardiography and MRI, there are a
      number of imaging features that may be used when interpreting and inferring valve
      pathology. This article discusses the role of currently available imaging
      modalities and the rationale for cardiac CT, while focusing on the CT
      interpretation of valvular heart disease with respect to the relevant
      pathophysiology and management options that have importance to the radiologist. A
      suggested method of post-processing image review is provided with reference to a
      variety of normal and pathological pictorial illustrations.

PMID- 18344274
TI  - The impact of 18F-FDG PET/CT on assessment of nasopharyngeal carcinoma at
      diagnosis.
AB  - The aim of this study was to determine whether the use of whole-body (18)F-fluoro
      2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET)/CT alters
      staging and management of nasopharyngeal carcinoma (NPC) when compared with
      current staging practice. 52 patients with Stage III-IV NPC without distant
      metastases on chest X-ray/CT, abdominal ultrasound or bone scan were recruited
      for the study. Whole-body (18)F-FDG PET/CT and MRI of the head and neck were
      performed. The scans were compared for extent of the primary tumour (PT),
      cervical nodal metastases (CNM) and distant metastases (DM). Any discordance in
      results was assessed with respect to staging and impact on management. MRI and
      (18)F-FDG PET/CT scans were discordant in 28 (54%) patients. There was
      discordance in the extent of PT at 28 sites; in all sites, MRI showed more
      extensive tumour involving the nasopharynx (n = 8), skull base (n = 14), brain (n
      = 4) and orbit (n = 2). There was also variation among the extent of CNM in four
      nodes of the retropharyngeal region, with the nodes being positive on MRI. (18)F
      FDG PET /CT did not identify any additional distant metastases but did identify a
      second primary tumour in the colon. The additional use of (18)F-FDG PET/CT did
      not "up-stage" the overall stage or change management in any patient. In
      conclusion, there is discordance between MRI and (18)F-FDG PET/CT, and the
      additional use of (18)F-FDG PET/CT for the current assessment of NPC at diagnosis
      does not appear to be justified in this cohort of patients.

PMID- 18344275
TI  - An investigation into methods of IMRT planning applied to breast radiotherapy.
AB  - The purpose of this study was to investigate methods used to modulate dose
      distributions in radiotherapy planning, to determine the fundamental features of
      these and to establish the attainable dose uniformity. Published modulation
      methods were categorized, and a simple physical model devised to predict the
      weight of the wedged beam and the relative dose distribution for each category.
      Each technique was applied to patient data with planning target volume sizes
      ranging from below 500 cm(3) to 2200 cm(3). The spatial distribution of high-dose
      regions in the breast, and maximum dose for the heart and lung, were determined
      for each plan. The dose uniformity was analysed by evaluating the volume of the
      breast (V(I)) receiving <95% and <105% of the prescribed dose. The difference
      between V(105%) and V(95%) for each method for each patient data set was also
      calculated. The simple model predicted the trend in percentage weight of the
      wedge beam and the form of the dose distribution in the transverse plane with the
      modulation method. Improvements in the dose uniformity were seen for the majority
      of modulation methods. The magnitude of the change was between 5.6% and 11.1%
      (p<0.05) of the breast volume for breast sizes above 500 cm(3). Some modulation
      methods introduced high dose at the chest wall. In conclusion, the majority of
      the methods improved dose uniformity for breast sizes of 500 cm(3) or greater. No
      method showed a clear advantage over the others. The use of modulation methods
      should be governed by consideration of its effects relative to a simple wedge
      plan.

PMID- 18344276
TI  - Re-defining rectal volume and DVH for analysis of rectal morbidity risk after
      radiotherapy for early prostate cancer.
AB  - Improved prostate cancer cure rates have been attributed to higher radiotherapy
      dose prescriptions delivered more safely by modern conformal/intensity-modulated
      radiotherapy (IMRT) methods. As the dose becomes more concentrated conformally on
      the prostate, the volume of the rectum "at risk" for damage becomes smaller and
      more focal on the anterior rectal wall between the upper and lower axial limits
      of the planning target volume (PTV). The rectal dose-volume histogram (DVH)
      traditionally studies the whole volume of the rectum, and such definition for
      "avoidance" planning presupposes that rectal tolerance depends on "whole organ"
      radiation tolerance (as might, for example, lung or kidney). However, rectal
      morbidity with modern prostate radiotherapy is determined by anterior rectal wall
      tolerance between the superior and inferior limits of the PTV; this, we argue, is
      not dependent on whole organ tolerance. Recent published studies attempting to
      improve rectal DVH definition have studied the rectal wall only and concluded
      that rectal wall DVH is more relevant than whole rectum. In this manuscript, it
      is first demonstrated that a large and more relevant difference exists when
      comparing whole rectal DVH to "PTV limits" rectal DVH. Secondly, when considering
      "PTV limits" rectal DVH, the wall vs whole perimeter comparison differs little.
      Furthermore, by adopting a "PTV limits" DVH, the inferior right quartile of the
      DVH accurately reflects the dose distribution to the most vulnerable section of
      the anterior rectal wall. With improving IMRT technologies, scrutiny of this part
      of the rectal DVH will most accurately predict rectal sparing - reflected in this
      manuscript by the less precipitous decline of the TomoTherapy DVH vs the three
      dimensional conformal DVH towards the maximum dose point received by the rectum.

PMID- 18344277
TI  - A dosimetric comparison between two intensity-modulated radiotherapy techniques:
      tomotherapy vs dynamic linear accelerator.
AB  - This manuscript describes a direct comparison between radiation treatment plans
      in terms of dosimetric outcomes created by two different IMRT systems:
      TomoTherapy HiArt and dynamic linac intensity-modulated radiotherapy (dIMRT).
      Three patient cases were selected (with disease in different anatomical areas):
      vertebral metastasis re-treatment, radical prostate therapy and an ethmoid
      sarcoma re-treatment. Each case presents significant and varying dosimetric
      difficulties with respect to avoidance of adjacent organs. The patients were each
      planned and treated at the Cromwell Hospital (London, UK) using the TomoTherapy
      HiArt system, with planning replicated at St Bartholomew's Hospital (London, UK)
      using Eclipse Treatment Planning System and a 6EX linac with a 120-leaf multileaf
      collimator (Varian Medical Systems). For both modalities, all treatment plans
      conformed to the stringent clinical dose constraints set. For the vertebral body
      re-treatment, both techniques demonstrated adequate and similar planning target
      volume (PTV) coverage and sparing of the spinal cord. The critical structure
      sparing and PTV coverage for the prostate treatment was again similar for both
      modalities. For re-treatment of the paediatric ethmoid sarcoma, tomotherapy was
      able to produce slightly better organ sparing whilst producing PTV coverage
      similar to linac dIMRT. The data presented in this manuscript demonstrate subtle
      dosimetric differences between the two techniques but no marked advantage with
      either system. Therefore, other factors may need to be considered when making a
      decision between tomotherapy and linac dIMRT.

PMID- 18344278
TI  - Validation of correction methods for the non-linear response of digital
      radiography systems.
AB  - Standard deviation is used as a measure of noise in digital images for quality
      control. For systems that have a non-linear response between pixel value and air
      kerma, the standard deviation of the pixel values will not be meaningful unless
      the image data is linearized using the response function of the system. Two
      methods are compared for estimating standard deviation without linearizing the
      image data. Method A estimates the true standard deviation by subtracting the
      corrected mean pixel value from the corrected sum of the mean pixel value and
      pixel standard deviation. Method B divides the pixel standard deviation by the
      point gradient of the response curve. The methods were tested using a range of
      digital radiographical systems with different response functions between pixel
      values and air kerma. The aim of this work was to measure the standard deviation
      and compare the accuracy of the two methods over a wide range of exposures. Both
      methods are easy to apply and require only basic software. Method A is considered
      satisfactory for routine quality assurance, as the error is generally <1%;
      however, the errors increase with reducing air kerma. Method B normally produces
      errors <0.2%. At low air kerma, the measured errors are up to 8% and 2% for
      Methods A and B, respectively. Method B is robust over a wide range of air kerma
      and is easily implemented.

PMID- 18344279
TI  - Rapidly enlarging mediastinal mass in a middle-aged patient with fever.

PMID- 18344280
TI  - Mechanosignal transduction coupling between endothelial and smooth muscle cells:
      role of hemodynamic forces.

PMID- 18344281
TI  - Serum response factor neutralizes Pur alpha- and Pur beta-mediated repression of
      the fetal vascular smooth muscle alpha-actin gene in stressed adult
      cardiomyocytes.
AB  - Mouse hearts subjected to repeated transplant surgery and ischemia-reperfusion
      injury develop substantial interstitial and perivascular fibrosis that was
      spatially associated with dysfunctional activation of fetal smooth muscle alpha
      actin (SM alpha A) gene expression in graft ventricular cardiomyocytes. Compared
      with cardiac fibroblasts in which nuclear levels of the Sp1 and Smad 2/3
      transcriptional-activating proteins increased markedly after transplant injury,
      the most abundant SM alpha A gene-activating protein in cardiomyocyte nuclei was
      serum response factor (SRF). Additionally, cardiac intercalated discs in heart
      grafts contained substantial deposits of Pur alpha, an mRNA-binding protein and
      known negative modulator of SRF-activated SM alpha A gene transcription.
      Activation of fetal SM alpha A gene expression in perfusion-isolated adult
      cardiomyocytes was linked to elevated binding of a novel protein complex
      consisting of SRF and Pur alpha to a purine-rich DNA element in the SM alpha A
      promoter called SPUR, previously shown to be required for induction of SM alpha A
      gene transcription in injury-activated myofibroblasts. Increased SRF binding to
      SPUR DNA plus one of two nearby CArG box consensus elements was observed in SM
      alpha A-positive cardiomyocytes in parallel with enhanced Pur alpha:SPUR
      protein:protein interaction. The data suggest that de novo activation of the
      normally silent SM alpha A gene in reprogrammed adult cardiomyocytes is linked to
      elevated interaction of SRF with fetal-specific CArG and injury-activated SPUR
      elements in the SM alpha A promoter as well as the appearance of novel Pur alpha
      protein complexes in both the nuclear and cytosolic compartments of these cells.

PMID- 18344282
TI  - The coiled-coil and nucleotide binding domains of the Potato Rx disease
      resistance protein function in pathogen recognition and signaling.
AB  - Plant genomes encode large numbers of nucleotide binding and leucine-rich repeat
      (NB-LRR) proteins, some of which mediate the recognition of pathogen-encoded
      proteins. Following recognition, the initiation of a resistance response is
      thought to be mediated by the domains present at the N termini of NB-LRR
      proteins, either a Toll and Interleukin-1 Receptor or a coiled-coil (CC) domain.
      In order to understand the role of the CC domain in NB-LRR function, we have
      undertaken a systematic structure-function analysis of the CC domain of the
      potato (Solanum tuberosum) CC-NB-LRR protein Rx, which confers resistance to
      Potato virus X. We show that the highly conserved EDVID motif of the CC domain
      mediates an intramolecular interaction that is dependent on several domains
      within the rest of the Rx protein, including the NB and LRR domains. Other
      conserved and nonconserved regions of the CC domain mediate the interaction with
      the Ran GTPase-activating protein, RanGAP2, a protein required for Rx function.
      Furthermore, we show that the Rx NB domain is sufficient for inducing cell death
      typical of hypersensitive plant resistance responses. We describe a model of CC
      NB-LRR function wherein the LRR and CC domains coregulate the signaling activity
      of the NB domain in a recognition-specific manner.

PMID- 18344283
TI  - EMB2473/MIRO1, an Arabidopsis Miro GTPase, is required for embryogenesis and
      influences mitochondrial morphology in pollen.
AB  - The regulation of mitochondrial biogenesis, subcellular distribution, morphology,
      and metabolism are essential for all aspects of plant growth and development.
      However, the molecular mechanisms involved are still unclear. Here, we describe
      an analysis of the three Arabidopsis thaliana orthologs of the evolutionarily
      conserved Miro GTPases. Two of the genes, MIRO1 and MIRO2, are transcribed
      ubiquitously throughout the plant tissues, and their gene products localize to
      mitochondria via their C-terminal transmembrane domains. While insertional
      mutations in the MIRO2 gene do not have any visible impact on plant development,
      an insertional mutation in the MIRO1 gene is lethal during embryogenesis at the
      zygote to four-terminal-cell embryo stage. It also substantially impairs pollen
      germination and tube growth. Laser confocal and transmission electron microscopy
      revealed that the miro1 mutant pollen exhibits abnormally enlarged or tube-like
      mitochondrial morphology, leading to the disruption of continuous streaming of
      mitochondria in the growing pollen tube. Our findings suggest that mitochondrial
      morphology is influenced by MIRO1 and plays a vital role during embryogenesis and
      pollen tube growth.

PMID- 18344284
TI  - The Arabidopsis P4-ATPase ALA3 localizes to the golgi and requires a beta-subunit
      to function in lipid translocation and secretory vesicle formation.
AB  - Vesicle budding in eukaryotes depends on the activity of lipid translocases (P(4)
      ATPases) that have been implicated in generating lipid asymmetry between the two
      leaflets of the membrane and in inducing membrane curvature. We show that
      Aminophospholipid ATPase3 (ALA3), a member of the P(4)-ATPase subfamily in
      Arabidopsis thaliana, localizes to the Golgi apparatus and that mutations of ALA3
      result in impaired growth of roots and shoots. The growth defect is accompanied
      by failure of the root cap to release border cells involved in the secretion of
      molecules required for efficient root interaction with the environment, and ala3
      mutants are devoid of the characteristic trans-Golgi proliferation of slime
      vesicles containing polysaccharides and enzymes for secretion. In yeast
      complementation experiments, ALA3 function requires interaction with members of a
      novel family of plant membrane-bound proteins, ALIS1 to ALIS5 (for ALA
      Interacting Subunit), and in this host ALA3 and ALIS1 show strong affinity for
      each other. In planta, ALIS1, like ALA3, localizes to Golgi-like structures and
      is expressed in root peripheral columella cells. We propose that the ALIS1
      protein is a beta-subunit of ALA3 and that this protein complex forms an
      important part of the Golgi machinery required for secretory processes during
      plant development.

PMID- 18344285
TI  - Plasma connective tissue growth factor is an independent predictor of end-stage
      renal disease and mortality in type 1 diabetic nephropathy.
AB  - OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue
      growth factor (CTGF) in a prospective study of patients with type 1 diabetes.
      RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with
      established diabetic nephropathy and 188 type 1 diabetic patients with persistent
      normoalbuminuria. Follow-up time was 12.8 years. Prediction of end-stage renal
      disease (ESRD) and mortality by plasma CTGF was analyzed in conjunction with
      conventional risk factors. RESULTS: Plasma CTGF was higher in patients with
      nephropathy than in patients with normoalbuminuria (median 381 [interquartile
      range 270-630] vs. 235 [168-353] pmol/l). In patients with nephropathy, elevated
      plasma CTGF was an independent predictor of ESRD (covariate-adjusted hazard ratio
      [HR] 1.6 [95% CI 1.1-2.5]) and correlated with the rate of decline in glomerular
      filtration rate (GFR) (cumulative R = 0.46). Area under the receiver operating
      characteristic curve for prediction of ESRD was 0.72. Plasma CTGF above a cutoff
      level of 413 pmol/l predicted ESRD with a sensitivity of 73% and a specificity of
      63% and was associated with a higher rate of decline in GFR (mean +/- SD 5.4 +/-
      4.9 vs. 3.3 +/- 3.5 ml/min per 1.73 m(2) per year). Moreover, in patients with
      nephrotic range albuminuria (>3 g/day), plasma CTGF was the only predictor of
      ESRD (covariate-adjusted HR 4.5 [2.0-10.4]). Plasma CTGF was an independent
      predictor also of overall mortality (covariate-adjusted HR 1.4 [1.1-1.7]). In
      contrast, in normoalbuminuric patients, plasma CTGF did not correlate with
      clinical parameters and did not predict outcome. CONCLUSIONS: Plasma CTGF
      contributes significantly to prediction of ESRD and mortality in patients with
      type 1 diabetic nephropathy.

PMID- 18344286
TI  - Use of 25-hydroxyvitamin D3 and dietary calcium to improve tenderness of beef
      from the round of beef cows.
AB  - The objective of this trial was to determine how 25-hydroxyvitamin D(3) (25-OH
      D(3)) supplementation, altering supplemental dietary calcium, or their
      combination influence postmortem biochemical and tenderness changes in muscles
      from the round of mature cows. Twenty-seven Angus cows (3 to 7 yr old) were
      allotted randomly to 9 pens with 3 cows per pen. Treatments were arranged in a 3
      x 3 factorial design with 3 dosages of 25-OH D(3) (0, 250, or 500 mg of 25-OH
      D(3) administered as a 1-time oral bolus 7 d before slaughter) and 3 percentages
      of supplemental limestone (0.5, 0.75, and 1.0%) replenished in the diet for 3 d
      before slaughter and after a 2-wk limestone withdrawal. Plasma samples were
      obtained during the feeding period. Upon slaughter, adductor, gracilus,
      pectineus, sartorius, semimembranosus, vastus intermedius, and vastus lateralis
      muscles were obtained and aged for 1, 3, or 7 d. Calcium concentrations were
      increased in plasma when 250 or 500 mg of 25-OH D(3) were administered (P </=
      0.05). Calcium concentrations in muscle increased (P </= 0.001) when 500 mg of 25
      OH D(3) were administered. Concentrations of 25-OH D(3) in meat and in plasma and
      1,25-dihydroxyvitamin D(3) [1,25-(OH)(2) D(3)] in plasma were increased when 25
      OH D(3) was administered (P </= 0.05). The percentage of limestone replenished in
      the diet had no effect on 25-OH D(3) or 1,25-(OH)(2) D(3) in meat or in plasma.
      Calpastatin activity was affected by treatments only in the gracilus and vastus
      intermedius muscles (P </= 0.05). Among all muscles and aging periods,
      calpastatin activity and intensity of troponin-T degradation product were related
      inversely. Results indicate that supplemental 25-OH D(3) has some influence on
      muscle characteristics known to improve tenderness, but improved tenderness was
      not observed.

PMID- 18344287
TI  - Timing of artificial insemination in postpartum beef cows following
      administration of the CO-Synch + controlled internal drug-release protocol.
AB  - This experiment was designed to compare pregnancy rates in postpartum beef cows
      resulting from fixed-time AI (FTAI) at 54 or 66 h after administration of the CO
      Synch + controlled internal drug-release (CIDR) protocol. Cows (n = 851) at 2
      locations over 2 yr (yr 1, n = 218 and 206; and yr 2, n = 199 and 228 at the 2
      locations, respectively) were stratified by age, BCS, and days postpartum to 1 of
      2 FTAI intervals. Cows were administered GnRH (100 mug, i.m.) and were equipped
      with a CIDR insert (1.38 g of progesterone) on d 0. Controlled internal drug
      release inserts were removed 7 d later at the time PGF(2alpha) (25 mg, i.m.) was
      administered (d 7). Continuous estrus detection was performed at location 2 by
      using the HeatWatch Estrus Detection System; the transmitters were fitted at the
      time of PGF(2alpha) and removed at the time of AI. Artificial insemination was
      performed at predetermined fixed times [54 h (FTAI 54; n = 424) or 66 h (FTAI 66;
      n = 427) after PGF(2alpha)] and all cows were administered GnRH (100 mug, i.m.)
      at AI. Two blood samples were collected on d -10 or -8 and immediately before
      treatment initiation to determine the pretreatment estrous cyclicity status of
      cows [progesterone >/=0.5 ng/mL (FTAI 54, 288/424 = 68%; FTAI 66, 312/427 = 73%;
      P = 0.07)]. Pregnancy rates were greater (P < 0.01) among cows that exhibited
      estrus than among those that did not (123/163 = 76% and 150/270 = 56%,
      respectively). There were no treatment x location interactions within year (P >
      0.10) for age, days postpartum, or BCS; thus, the results were pooled for the
      respective treatments. Pregnancy rates were greater for FTAI 66 than FTAI 54 (P =
      0.05; 286/426 = 67% vs. 257/424 = 61%, respectively). Pregnancy rates resulting
      from FTAI did not differ between year (P = 0.09), farm (P = 0.80), AI sire (P =
      0.11), or technician (P = 0.64). There was no difference between pregnancy rates
      resulting from FTAI based on pretreatment cyclicity status (P = 0.30), and there
      was no difference between treatments in final pregnancy rates (P = 0.77). In
      summary, pregnancy rates resulting from FTAI following CO-Synch + CIDR at 66 h
      were greater than those resulting from FTAI at 54 h.

PMID- 18344288
TI  - Use of 25-hydroxyvitamin D3 and vitamin E to improve tenderness of beef from the
      longissimus dorsi of heifers.
AB  - The objective of this trial was to determine whether a single bolus of 25
      hydroxyvitamin D(3) (25-OH D(3)), vitamin E, or a combination of the 2 would
      improve the tenderness of steaks from the LM of beef heifers. Forty-eight Angus
      crossbred heifers were allotted randomly to 8 pens. Six heifers were in each pen,
      and there were 2 pens per treatment. The 4 treatments included control (no 25-OH
      D(3) or vitamin E); 25-OH D(3) (500 mg of 25-OH D(3) administered as a one-time
      oral bolus 7 d before slaughter); vitamin E (1,000 IU of vitamin E administered
      daily as a top-dress for 104 d before slaughter); or combination (500 mg of 25-OH
      D(3) administered as a one-time oral bolus 7 d before slaughter and 1,000 IU of
      vitamin E administered daily as a top-dress for 104 d before slaughter). Blood
      samples were obtained on the day that heifers were allotted to treatments, on the
      day 25-OH D(3) was administered, and on the day before slaughter. Plasma calcium
      concentration was increased when 25-OH D(3) was administered with or without
      vitamin E (P < 0.007). In LM, calcium concentration tended to increase (P = 0.10)
      when 25-OH D(3) was administered alone but not when 25-OH D(3) was administered
      with vitamin E. Concentrations of 25-OH D(3) and 1,25-dihydroxyvitamin D(3) in
      plasma were increased when 25-OH D(3) was administered with or without vitamin E
      (P < 0.001). Steaks from heifers treated with 25-OH D(3) or vitamin E, but not
      both, tended to have lower Warner-Bratzler shear force than steaks in the control
      group at 14 d postmortem (P = 0.08). Postmortem protein degradation as measured
      by Western blot of the 30-kDa degradation product of troponin-T was increased
      with all treatments after 3 d postmortem (P </= 0.07), but not at 7 or 14 d
      postmortem. Unexpectedly, the use of 500 mg of 25-OH D(3) fed as an oral bolus 7
      d before slaughter or 1,000 IU of vitamin E administered daily for 104 d before
      slaughter alone, but not in combination, effectively decreased Warner-Bratzler
      shear force.

PMID- 18344289
TI  - Effect of vitamin A restriction on carcass characteristics and immune status of
      beef steers.
AB  - Sixty-eight Angus-based steers (224 +/- 7.6 kg of BW) were used to evaluate the
      effects of a prolonged dietary vitamin A restriction on marbling and
      immunocompetency. Steers were allotted randomly to 1 of 2 treatments: LOW (no
      supplemental vitamin A) and HIGH (diet supplemented with 2,200 IU of vitamin A/kg
      of DM). Diets contained 60% high-moisture corn, 20% roasted soybeans, 10% corn
      silage, and 10% of a protein supplement. Steers were penned and fed individually.
      For the first 141 d, steers were program-fed to achieve a gain of 1.1 kg/d. The
      last 75 d of the experiment, steers were offered feed for ad libitum intake. At
      slaughter, serum and liver samples were taken to determine their retinol content.
      To evaluate immunocompetency, 10 steers per treatment were selected randomly on d
      141 and received an ovalbumen vaccine, and 21 d later, the steers were
      revaccinated. On d 182, blood samples were taken from the vaccinated steers to
      determine serum antibody titers by ELISA. Steers were slaughtered after 216 d on
      feed. Carcass characteristics were determined, and LM samples were taken for
      composition analysis. Subcutaneous fat samples were taken for fatty acid
      composition analysis. Performance (ADG, DMI, and G:F) was not affected by vitamin
      A restriction (all P > 0.10). Hot carcass weight, 12th-rib fat, and yield grade
      did not differ between LOW and HIGH steers (all P > 0.10). Marbling score (LOW =
      574 vs. HIGH = 568, P = 0.79) and i.m. fat (LOW = 5.0 vs. HIGH = 4.7% ether
      extractable fat, P = 0.57) were not increased by vitamin A restriction. Serum
      (LOW = 18.7 vs. HIGH = 35.7 mug/dL, P < 0.01) and liver (LOW = 6.3 vs. HIGH =
      38.1 mug/g, P < 0.01) retinol levels were lower in LOW steers compared with HIGH
      steers at slaughter. Response to ovalbumin vaccination was not affected by
      vitamin A restriction (LOW = 13.1 vs. HIGH = 12.8 log(2) titers, P = 0.60).
      Slight changes in the fatty acid profile of s.c. fat of the steers were detected.
      A greater proportion of MUFA (LOW = 41.7 vs. HIGH = 39.9%, P = 0.03) and fewer
      SFA (LOW = 47.1 vs. 48.7, P = 0.03) were observed in vitamin A-restricted steers.
      This suggests that vitamin A restriction may affect the activity of desaturase
      enzyme (desaturase activity index, LOW = 46.9 vs. HIGH = 44.9, P = 0.01). Feeding
      a low vitamin A diet for 216 d to Angus-based steers did not affect performance,
      marbling score, or animal health and immunocompetency. Slight changes in the
      fatty acid profile of s.c. fat were observed, suggesting that vitamin A
      restriction may have affected desaturase enzyme activity.

PMID- 18344290
TI  - Interpopulation and intrapopulation maternal lineage genetics of the Lanyu pig
      (Sus scrofa) by analysis of mitochondrial cytochrome b and control region
      sequences.
AB  - The Lanyu pig is an indigenous breed from the Lanyu Islet, which is southeast of
      Taiwan. Two herds of Lanyu pigs were introduced from the Lanyu Islet into Taiwan
      in 1975 and 1980. The current population of conserved Lanyu pigs consists of only
      44 animals with unknown genetic lineage. The Lanyu pig possesses a distinct
      maternal genetic lineage remote from Asian and European pigs. The present study
      aimed to understand the phylogenetic relationship among conserved Lanyu, Asian,
      and European type pigs based on the cytochrome b coding gene, to ascertain the
      maternal lineage and genetic diversity within the conserved Lanyu pigs, and to
      address whether genetic introgression from exotic or Formosan wild pigs had
      occurred in the conserved Lanyu pigs. Entire mitochondrial genomes of both types
      of Lanyu pig comprised 2 ribosomal RNA, 22 transfer RNA, and 13 protein-coding
      genes. Only 2 haplotypes of the mitochondrial DNA (mtDNA) control region and
      cytochrome b were identified in the conserved Lanyu pig herds. When maximum
      likelihood trees were constructed, the Type I Lanyu mitochondrial genes formed a
      unique clade with a large pairwise distance of both cytochrome b and the control
      region from Asian and European type breeds, Formosan wild pigs, and exotic
      breeds. Significant loss of genetic diversity of mtDNA within the conserved Lanyu
      pigs was demonstrated by low haplotype and nucleotide diversities, supported by
      Fu and Li's D* neutrality test (1.44055; P < 0.05). The mtDNA control region
      sequences of extant pigs in the Lanyu Islet, however, showed high haplotype and
      nucleotide diversity, and clustered with exotic pigs. These results indicate no
      maternal lineage mtD-NA gene introgression from Formosan wild pigs and introduced
      exotic pigs to conserved Type I Lanyu pigs, and a severe loss of heterozygosity
      of mtDNA in conserved Lanyu pigs. The remaining extant pigs on the Lanyu Islet
      have been introgressed with exotic breeds. Strategies for future conservation of
      native Lanyu pigs are now even more urgent and important.

PMID- 18344291
TI  - A regional evaluation of the effect of fiber type in gestation diets on sow
      reproductive performance.
AB  - A cooperative regional research study using 194 sows, from which data were
      collected from 381 litters, was conducted at 3 research stations to determine the
      effects of added psyllium (a concentrated fiber source) or soybean hulls to
      gestation diets on reproductive performance of sows and preweaning performance of
      their pigs. Primiparous and multiparous sows were allotted to the 3 treatments of
      control (corn and soybean meal-based), 0.30% psyllium, or 20% soybean hulls. Sows
      fed the control and 0.30% psyllium diets were provided 1.82 kg/d, and sows fed
      the 20% soybean hulls diet were provided 2.0 kg/d to equalize ME, Lys, Ca, P, and
      vitamin and trace mineral intake. Treatments 1 to 3 had 130, 130, and 121 litters
      per treatment from 64, 64, and 63 sows, respectively. Gestating sows fed psyllium
      had a greater (P < 0.01 to 0.10) d 110 gestation, farrowing, weaning, and 17 d
      postpartum BW and gestation ADG compared with sows fed soybean hulls. Sows fed
      psyllium also had a greater (P < 0.10 and 0.08) d 110 gestation BW and gestation
      ADG than the control sows. Sows fed soybean hulls had a reduced (P < 0.06)
      farrowing BW compared with the control sows. Sows fed psyllium weaned lighter (P
      < 0.09) pigs than sows fed the control diet. Litter size was not affected (P >
      0.10) by diet. Sows fed psyllium had a reduced (P < 0.03) feed intake compared
      with sows fed soybean hulls for d 5 to 7 postpartum, and sows fed the control
      diet were intermediate. Fecal scores (1 to 5 with 1 = dry and 5 = watery) were
      greater (P < 0.001) and DM content was less (P < 0.001 to 0.01) in the feces of
      sows fed soybean hulls compared with sows fed psyllium or the control diet on d
      112 of gestation and d 4 postpartum. Fecal scores were greater (P < 0.10) and
      fecal DM content was less (P < 0.02) in sows fed psyllium compared with sows fed
      the control diet only on d 4 postpartum. In summary, sows fed soybean hulls
      during gestation had reduced BW compared with sows fed the control diets. In
      contrast, sows fed psyllium had an increased BW.

PMID- 18344292
TI  - Expression of matrix metalloproteinases during vascularization and ossification
      of normal and impaired avian growth plate.
AB  - Enzymes of the matrix metalloproteinase (MMP) family regulate angiogenesis and
      are involved in the endochondral ossification process. Tibial dyschondroplasia
      (TD) and rickets are 2 disorders associated with impairments in this process,
      mainly in the vascularization of the avian growth plate. In this paper, we
      induced TD and rickets and studied the expression patterns of 4 members of the
      MMP family known to be important for endochondral ossification, MMP-2, 3, 9, and
      13, in normal and impaired avian growth plates. The expression of MMP-3, 9, and
      13 was reduced in the lesions and lined up parallel to the expulsion of blood
      vessels, which was extended up to the border of the lesion, but did not penetrate
      into it. Matrix metallopro-teinase-2 was not expressed in the TD lesion but was
      overexpressed in the rachitic lesion. We also studied the differentiation stage
      of the chondrocytes populating the lesions and found that the rachitic lesions
      were populated with proliferative chondrocytes, whereas the TD lesions were
      filled with chondrocytes that presented both proliferative and hypertrophic
      markers. These results suggest that MMP-3, 9, and 13 play a role in the
      vascularization and ossification processes, whereas MMP-2 is related to
      chondrocyte differentiation and may be involved in cartilage remodeling in the
      avian growth plate.

PMID- 18344293
TI  - AMP-activated protein kinase and adipogenesis in sheep fetal skeletal muscle and
      3T3-L1 cells.
AB  - Marbling, or i.m. fat, is an important factor determining beef quality. Both
      adipogenesis and hypertrophy of existing adipocytes contribute to enhanced
      marbling. We hypothesized that the fetal stage is important for the formation of
      i.m. adipocytes and that AMP-activated protein kinase (AMPK) has a key role in
      adipogenesis during this stage. The objective of this study was to assess the
      role of AMPK in adipogenesis in fetal sheep muscle and 3T3-L1 cells. Nonpregnant
      ewes were randomly assigned to a control (Con, 100% of NRC recommendations, n =
      7) or overfed (OF, 150% of NRC, n = 7) diet from 60 d before to 75 d after
      conception, when the ewes were killed. The fetal LM was collected at necropsy for
      biochemical analyses. The activity of AMPK was less in the fetal muscle of OF
      sheep. The expression of peroxisome proliferator-activated receptor (PPAR)gamma,
      a marker of adipogenesis, was greater in OF fetal muscle compared with Con fetal
      muscle. To further show the role of AMPK in adipogenesis, we used 3T3-L1 cells.
      The 3T3-L1 cells were incubated in a standard adipogenic medium for 24 h and 10
      d. Activation of AMPK by 5-aminoimidazole-4-car-boxamide-1-beta-d-ribonucleoside
      dramatically inhibited the expression of PPARgamma and reduced the presence of
      adipocytes after 10 d of differentiation. Inhibition of AMPK by compound C
      enhanced the expression of PPARgamma. In conclusion, these data show that AMPK
      activity is inversely related to adipogenesis in fetal sheep muscle and 3T3-L1
      cells.

PMID- 18344294
TI  - ASAS Centennial Paper: contributions in the Journal of Animal Science to
      understanding cattle metabolic and digestive disorders.
AB  - Acute and subacute ruminal acidosis, bloat, liver abscesses, and
      polioencephalomalacia (PEM) were reviewed with respect to contributions published
      in the Journal of Animal Science (JAS) regarding these metabolic and digestive
      disorders in beef cattle. Increased grain feeding and expansion of the feedlot
      industry in the 1960s led to considerable research on acidosis, and early
      publications defined ruminal changes with acute acidosis. The concept of subacute
      acidosis was developed in the 1970s. Significant research was published during
      the 1980s and 1990s on adaptation to high-grain diets, effects of ionophores, and
      the development of model systems to study ruminal and metabolic changes in
      acidosis. Since 2000, JAS publications on acidosis have largely focused on
      individual animal variability in response to acid loads and the role of
      management strategies in controlling acidosis. Increased grain feeding also was
      associated with an increase in the incidence of liver abscesses, which were
      quickly linked to insults to the ruminal epithelium associated with acidosis. The
      role of antibiotics, particularly tylosin, in decreasing the incidence and
      severity of liver abscesses was a significant contribution of JAS publications
      during the 1970s and 1980s. Papers on bloat were among the earliest published in
      JAS related to metabolic and digestive disorders in cattle. Noteworthy
      accomplishments in bloat research chronicled in JAS include the nature of ruminal
      contents in legume and feedlot bloat, the role of plant fractions and microbial
      populations in the development of bloat, and the efficacy of poloxalene,
      ionophores, and, more recently, condensed tannins in decreasing the incidence and
      severity of bloat. Although less research has been published on PEM in JAS, early
      publications highlighting the association between PEM and ruminal acidity and the
      role of thiaminase in certain forms of the disorder, as well as more recent
      publications related to the role of sulfur in the development of PEM, are
      noteworthy contributions. Since the 1940s, outstanding and often-cited review
      articles have made JAS a highly visible source of information on these disorders.
      Thus, JAS has played a significant role as a repository for information
      pertaining to metabolic and digestive disorders in cattle and other ruminants,
      and it will no doubt continue to be a premier resource for information on these
      conditions during the second century of the American Society of Animal Science.

PMID- 18344295
TI  - Effects of long- or short-term exposure to a calf identified as persistently
      infected with bovine viral diarrhea virus on feedlot performance of freshly
      weaned, transport-stressed beef heifers.
AB  - A single experiment with a completely randomized design was conducted to evaluate
      the effects of long- or short-term exposure to a calf identified as persistently
      infected with bovine viral diarrhea virus (PI-BVD) on feedlot performance and
      carcass characteristics of freshly weaned, transport-stressed beef heifers. Two
      hundred eighty-eight heifers that had been vaccinated for BVD before weaning and
      transport were processed and given a metaphylactic antibiotic treatment at
      arrival and were fed common receiving, growing, and finishing diets for a 215-d
      period. Treatments were designed to directly or adjacently expose the cattle to a
      PI-BVD heifer. Directly exposed treatments were 1) negative control with no PI
      BVD calf exposure (control), 2) PI-BVD calf commingled in the pen for 60 h and
      then removed (short-term exposure), and 3) PI-BVD calf commingled in the pen for
      the duration of the study (long-term exposure); and spatially exposed treatments
      were 1) negative control with no PI-BVD calf exposure (adjacent pen control), 2)
      PI-BVD calf commingled in the adjacent pen for 60 h and then removed (adjacent
      pen short-term exposure), and 3) PI-BVD calf commingled in the adjacent pen for
      the duration of the study (adjacent pen long-term exposure). Exposure to a PI
      calf transiently (60 h) or for the duration of the feeding period (215 d) did not
      affect (P > or = 0.25) final BW compared with heifers that were not exposed.
      Neither period nor overall DMI was affected (P > or = 0.37) by PI-BVD calf
      exposure, and no differences (P > or = 0.44) were observed between short- and
      long-term exposed heifers in the direct or spatially exposed groups. Likewise,
      total trial ADG was not affected (P > or = 0.36) and overall efficiency of gain
      (P > or = 0.19) was unaffected by PI-BVD calf exposure in the direct or spatially
      exposed groups. The results from this study suggest that exposing previously
      vaccinated, freshly weaned, transport- stressed beef calves to a calf that is
      persistently infected with bovine viral diarrhea virus has little, if any, marked
      effects on health, performance, or carcass characteristics.

PMID- 18344296
TI  - Effects of dried distillers grains with solubles on growing and finishing pig
      performance in a commercial environment.
AB  - Three experiments were conducted to determine the optimal level of dried
      distiller grains with solubles (DDGS) from a common ethanol manufacturing
      facility and to determine the potential interactions between dietary DDGS and
      added fat on performance and carcass characteristics of growing and finishing
      pigs. All experiments were conducted at the same commercial facility and used
      DDGS from the same ethanol manufacturing facility. In Exp. 1, a total of 1,050
      pigs (average initial BW 47.6 kg), with 24 to 26 pigs per pen and 7 pens per
      treatment, were fed diets containing 0 or 15% DDGS and 0, 3, or 6% added choice
      white grease in a 2 x 3 factorial arrangement in a 28-d growth study. Overall,
      there were no DDGS x added fat interactions (P >/= 0.14). There was an
      improvement (linear, P < 0.01) in ADG and G:F as the percentage of added fat
      increased. There was no difference (P = 0.74) in growth performance between pigs
      fed 0 or 15% DDGS. In Exp. 2, a total of 1,038 pigs (average initial BW 46.3 kg),
      with 24 to 26 pigs per pen and 10 pens per treatment, were fed diets containing
      0, 10, 20, or 30% DDGS in a 56-d growth study. Pigs fed diets containing DDGS had
      a tendency for decreased ADG and ADFI (both linear, P = 0.09 and 0.05,
      respectively), but the greatest reduction seemed to occur between pigs fed 10 and
      20% DDGS. In Exp. 3, a total of 1,112 pigs (average initial BW 49.7 kg), with 25
      to 28 pigs per pen and 9 pens per treatment, were used in a 78-d growth study to
      evaluate the effects of increasing DDGS (0, 5, 10, 15, or 20%) in the diet on pig
      growth performance and carcass characteristics. From d 0 to 78, ADG and ADFI
      decreased linearly (P </= 0.04) with DDGS level, but the greatest reduction
      seemed to occur between pigs fed 15 and 20% DDGS. Efficiency of gain tended to
      improve (P = 0.06) when DDGS were included in the diet. There was no effect of
      DDGS (P = 0.22) on loin depth. Carcass weight and percentage yield decreased
      (linear, P </= 0.04) with increasing levels of DDGS in the diet. Backfat and fat
      free lean index tended to decrease (linear, P </= 0.09) with increasing levels of
      DDGS in the diet. In conclusion, finishing pigs raised under commercial
      production conditions can be fed 10 to 15% DDGS from the source evaluated in this
      study before growth rate is compromised.

PMID- 18344297
TI  - Conjugated linoleic acid content in adipose tissue of calves suckling beef cows
      on pasture and supplemented with raw or extruded soybeans.
AB  - The concentration of CLA in adipose tissue can be increased in ruminants by
      feeding pasture and extruded soybeans. The objective of this study was to
      evaluate maternal supplementation of raw (RS) or extruded (ES) soybeans on the
      concentrations of CLA in milk fat of cows and s.c. adipose tissue of suckling
      calves. Thirty-two spring-calving cows (BW 624 +/- 76 kg; BCS 3.5 +/- 0.4; mean
      +/- SD) and calves (BW 127 +/- 15 kg) were separated into 2 groups. Cows were
      distributed to have 8 calves of each sex in both groups. When animals were turned
      out to pasture, dams received 2 kg/d of either RS or ES. Dietary treatments had
      no effect on average milk intake (P = 0.22) and pasture forage intake (P = 0.13)
      for calves over the course of the grazing season. As a result, no effect of
      treatments was observed on ADG (P = 0.26). At weaning, milk fat content of CLA
      reached 15.4 and 24.2 mg/g of total fatty acids for cows fed RS and ES,
      respectively (P = 0.02). The CLA concentrations in adipose tissue were 16.9 and
      25.0 mg/g of total fatty acids for calves suckling dams fed RS and ES,
      respectively (P < 0.001). Overall, results demonstrated supplementing grazing
      cows with ES increased CLA content in milk and adipose tissue of suckling calves.

PMID- 18344298
TI  - Evaluation of NutriDense low-phytate corn and added fat in growing and finishing
      swine diets.
AB  - Two experiments were conducted to evaluate the effects of NutriDense low-phytate
      corn in conjunction with increasing added dietary fat on growing and finishing
      pig performance. Diets in both experiments were corn-soybean meal-based, with
      yellow dent or NutriDense low-phytate corn and 0, 3, or 6% added choice white
      grease arranged in a 2 x 3 factorial design. There were 25 to 28 pigs per pen and
      7 pens (replications) per treatment in both experiments. In Exp. 1, a total of
      1,162 gilts with an initial BW of 44.6 kg were used in a 28-d growth study. A
      constant true ileal digestible (TID) Lys:ME ratio of 2.80 g/Mcal and available
      P:ME ratio of 0.90 g/Mcal were maintained in all treatment diets. Overall (d 0 to
      28), there were no corn source x added fat interactions (P >/= 0.79). Regardless
      of corn source, ADG and G:F increased (linear, P = 0.03) with increasing added
      fat. There were no differences (P >/= 0.34) in pig growth performance between
      those fed NutriDense low-phytate or yellow dent corn. In Exp. 2, a total of 1,128
      gilts with an initial BW of 81.6 kg were used in a 28-d growth study. A constant
      TID Lys:ME ratio of 2.15 g/Mcal of ME and available P:ME ratio of 0.75 g/Mcal
      were maintained in all treatment diets. Overall (d 0 to 28), there was a tendency
      (P = 0.07) for a corn source x added fat interaction for G:F, which can be
      explained by the improved G:F in pigs fed yellow dent corn only when 6% fat was
      added to the diet, whereas G:F was improved at both 3 and 6% added fat in pigs
      fed NutriDense low-phytate corn. There were no differences (P >/= 0.18) in growth
      performance between pigs fed NutriDense low-phytate or yellow dent corn. These
      results indicate that increasing added fat improved growth performance regardless
      of the corn source. In addition, growth performance was similar for pigs fed
      NutriDense low-phytate or yellow dent corn.

PMID- 18344299
TI  - Source of dietary lipid may modify the immune response in stressed feeder cattle.
AB  - Five studies were conducted to evaluate the effects of lipid source on
      performance and health of stressed feeder cattle. A total of 332 heifers (195 +/-
      2.37 kg initial BW) in trial 1 and 336 heifers (206 +/- 1.70 kg initial BW) in
      trial 2 were fed diets containing ground flaxseed (FLAX), rolled full-fat
      soybeans (SOY), or tallow (TAL) at 13, 20, or 4%, respectively (DM basis). All
      diets were formulated to be isonitrogenous and isocaloric. The ADG and G:F for
      the first 7 d and for the entire feeding period were greater (P < 0.05) for TAL
      and FLAX than for SOY. Percentage of animals treated and retreated for bovine
      respiratory disease did not differ among dietary treatments. The FLAX treatment
      increased (P < 0.05) total n-3 PUFA concentrations in the plasma, whereas SOY
      increased (P < 0.05) plasma concentrations of total n-6 PUFA. In trial 3, 18
      steers were individually fed diets containing TAL and 18 steers were fed a diet
      containing SOY (20% of DM). In trials 4 and 5, 18 steers were individually fed
      diets containing TAL and 18 steers were fed diets containing FLAX (12.9% of DM).
      On d 14 and 17 of study 3, 4, and 5, 16 steers from each dietary treatment were
      injected i.v. with Escherichia coli O55:B5 lipopolysaccharide (LPS), and 2 steers
      from each diet were injected with saline. Rectal temperatures after LPS challenge
      were lower (P < 0.05) for SOY and FLAX than for TAL, and plasma TNF was greater
      (P < 0.05) for SOY than for TAL. Serum haptoglobin and blood fibrinogen increased
      and white blood cell count decreased in response to LPS, but none of these
      variables was affected by treatment. Although this research failed to measure an
      effect of lipid source on feedlot morbidity or mortality, these studies indicate
      that altering the source and type of dietary fatty acids may modify the immune
      response in stressed feeder cattle and that performance may be hindered by
      feeding full-fat soybeans to receiving cattle.

PMID- 18344300
TI  - Changes of activity and mRNA expression of urea cycle enzymes in the liver of
      developing Holstein calves.
AB  - Urea is an important reutilizable nitrogen source for the ruminant and is mainly
      synthesized through the urea cycle in the liver. The cycle is undertaken by 5
      enzymes: carbamoyl phosphate synthetase (CPS), ornithine transcarbamoylase (OTC),
      arginino-succinate synthetase (AS), argininosuccinate lyase (AL), and arginase.
      The purpose of this study was to investigate changes in the activity of the
      enzymes and mRNA expression, given that previous observations have indicated an
      increase in plasma urea concentrations with age in Holstein calves. First, plasma
      concentrations of metabolites and hormones were determined in calves at 1, 3, 8,
      13, and 19 wk of age (n = 4, weaned at 6 wk of age). The plasma concentration of
      urea drastically increased after weaning (P < 0.001). The plasma concentration of
      glucose was lowest at 8 wk. The plasma concentration of IGF-I gradually increased
      with age, although those of NEFA, glucagon, and cortisol decreased (P < 0.001).
      Concentrations of triglyceride, alpha-amino nitrogen, growth hormone, and insulin
      did not change significantly with age of the calf. Next, using the liver tissues
      taken from calves at 2, 13, and 19 wk of age (n = 4 to 6 at each time point,
      weaned at 6 wk of age), we measured the activity and mRNA expression of the
      enzymes by biochemical methods and quantitative reverse transcription-PCR,
      respectively. The activities of CPS (P < 0.001), OTC (P = 0.001), and AS (P =
      0.015) increased with age, whereas AL (P = 0.003) decreased. Although mRNA
      expression was decreased with age for AL (P = 0.002) and arginase (P = 0.007), no
      significant change was observed for CPS, OTC, or AS mRNA expression. We conclude
      that the increased urea production in the liver may be explained not only by an
      increase in the activities of the urea cycle enzymes, but also by increased
      ammonia production by rumen fermentation and gluconeogenesis from amino acids
      around weaning time.

PMID- 18344301
TI  - Transportation of young beef bulls alters circulating physiological parameters
      that may be effective biomarkers of stress.
AB  - Transportation causes stress in cattle that may alter numerous physiological
      variables with a negative impact on production and health. The objectives of the
      current study were to investigate the physiological effects of truck
      transportation and to characterize a pattern of phenotypes in the circulation
      that may aid in the early identification of stress-susceptible animals that often
      succumb to severe respiratory disease. Thirty-six young beef bulls (Aberdeen
      Angus, n = 12; Friesian, n = 12; and Belgian Blue x Friesian, n = 12) were
      subjected to a 9-h truck transportation by road. Blood (10 mL) was collected at 
      24, 0, 4.5, 9.75, 14.25, 24, and 48 h relative to the initiation of
      transportation (0 h). Plasma was collected for the assay of various metabolic,
      inflammatory, and steroid variables, and total leukocyte counts were determined
      in whole blood at each time point. Body weight and rectal temperature were
      recorded at -24, 9.75, and 48 h. Transportation decreased measures of protein
      metabolism in the plasma, including albumin (P = 0.002), globulin (P < 0.001),
      urea (P = 0.006), and total protein (P < 0.001), and increased creatine kinase (P
      < 0.001). The energy substrate beta-hydroxybutyrate was not changed (P = 0.27).
      Acute phase proteins haptoglobin and fibrinogen were both decreased (P < 0.001),
      whereas total leukocyte counts were elevated (P = 0.002). Circulating steroid
      concentrations were altered, because a classical acute increase in plasma
      cortisol was observed with the onset of transit (P < 0.001), in association with
      a decrease in dehydroepiandrosterone (P = 0.07), resulting in a profound increase
      in cortisol:dehydroepiandrosterone ratio (P < 0.001). Plasma testosterone was
      decreased, whereas plasma progesterone was increased (P < 0.001) in association
      with the increase in cortisol (P < 0.001). There was also an effect of breed for
      all variables except plasma urea, creatine kinase, and testosterone, perhaps
      indicating that a genetic component contributed to the physiological response to
      transportation stress, although without any clear trend. Taken together, this
      profile of physiological variables in the circulation of transportation-stressed
      bulls may aid in the future detection of disease-susceptible cattle after
      transportation. Further research to validate these potential biomarkers is
      necessary.

PMID- 18344302
TI  - Effects of dietary supplementation of an enzyme blend on the ileal and fecal
      digestibility of nutrients in growing pigs.
AB  - The objective of this experiment was to determine the effect of a beta-glucanase
      protease enzyme blend product (EBP) on fecal digestibility (FD), apparent ileal
      digestibility (AID), standardized ileal digestibility, and digestibility in the
      hindgut of growing pigs. Twelve ileal-cannulated, growing barrows (38.2 +/- 0.5
      kg) were housed in individual metabolism crates, blocked by previous feed intake
      into 3 groups with 4 pigs each, and randomly assigned to 1 of 4 treatments within
      a square (group) of 3 replications of 4 x 4 Latin square design. Treatments were
      basal diet (Basal), Basal + 0.05% of EBP (0.05% EBP), Basal + 0.10% of EBP (0.10%
      EBP), and hydrolyzed casein for measurement of endogenous amino acids. The Basal
      diet consisted of corn and soybean meal and was calculated to have 3.36 Mcal of
      ME/kg and 1.1% of total lysine, as-fed basis. Feed intake of each replicate of
      the Latin square during the first period was 85% of the minimum feed intake of
      the 4 pigs during the preliminary period and was equalized within each square.
      The feeding level was increased by 100 g/d in each subsequent period. Each of the
      experimental periods was 14 d, including 4 d of dietary adaptation, 5 d of fecal
      collection, 3 d of transition period, and 2 d of ileal collection. Ileal
      effluents were collected continuously for the same 12-h interval each day. Pigs
      fed the EBP demonstrated increased (P < 0.05) FD of DM, OM, energy, CP, nonfiber
      carbohydrate, total dietary fiber, insoluble dietary fiber, acid-hydrolyzed fat,
      ash, Ca, and P compared with pigs fed Basal. The AID of NDF and hemicellulose was
      increased (P < 0.05) by supplying the EBP either at 0.05 or 0.10% in the diets,
      but AID of DM and energy was not increased. The AID of acid-hydrolyzed fat tended
      to be greater (P = 0.051) for the pigs fed the EBP than for those fed Basal.
      Ileal digestibility of most amino acids was not affected by treatment, but the
      EBP reduced the apparent and standardized digestibility of methionine, alanine,
      and serine (P < 0.05). The difference between FD and AID of hemicellulose was
      lower (P < 0.05) for the pigs fed the EBP than for those fed Basal. These results
      demonstrated that the EBP fed to growing pigs improved the FD of DM, OM, energy,
      CP, nonfiber carbohydrate, total dietary fiber, acid-hydrolyzed fat, Ca, and P,
      and the AID of NDF and hemi-cellulose, but the standardized ileal digestibility
      of amino acids was not improved by supplying the EBP in corn-soybean meal-based
      diets of growing pigs.

PMID- 18344303
TI  - Potato (Solanum tuberosum L. cv. Gogu valley) protein as a novel antimicrobial
      agent in weanling pigs.
AB  - A total of 280 weaned pigs (Landrace x Yorkshire x Duroc) were used in a 28-d
      growth study to investigate the effect of feeding different levels of potato
      proteins on growth performance, nutrient digestibility, immune response, small
      intestinal morphology, and bacterial populations in feces and large intestine.
      Pigs (initially 6.42 +/- 0.74 kg of BW and 23 +/- 3 d of age) were randomly
      allotted to 5 treatments on the basis of BW, each treatment composed of 4 pens,
      each pen having 14 pigs. Dietary treatments included positive control (PC; basal
      diet + 150 mg/kg apramycin and 10 mg/ kg colistin sulfate); and potato protein
      (PP), consisting of the basal diet with 0, 0.25, 0.50, or 0.75% of potato
      protein. Diets were fed in 2 phases: phase I (d 0 to 14 postweaning) and phase 2
      (d 14 to 28 postweaning). Potato protein was extracted from a value-added type of
      the new potato variety, Solanum tuberosum L. cv. Gogu valley, and was shown to
      have a minimum inhibitory concentration of 300 to 500 mug/mL. Performance of PC
      was compared with 0.25 to 0.75% PP, whereas linear and quadratic trends of
      increasing PP (0 to 0.75% PP) were tested. Over the 28-d trial, pigs fed the PC
      diets showed improved overall ADG (P < 0.05) and G:F (P = 0.090) compared with
      pigs fed PP, whereas increasing levels of PP linearly improved ADG (P < 0.05),
      ADFI (P = 0.052), and G:F (P = 0.098). The digestibility of DM and CP in both the
      phases was greater in PC than PP, and feeding of PP linearly improved the DM
      digestibility (P < 0.05) in phase II. The bacterial populations in the feces of
      pigs fed PC and PP were comparable, except for total bacteria and coliform
      bacteria in the feces at d 14 and 28, which were decreased in PC; and feeding of
      PP was effective in linearly reducing the populations of microbes in feces and
      contents of cecum, colon, and rectum. There was linear increase (P < 0.10) in
      skin-fold thickness in response to phytohemagglutinin with an increase in PP
      levels. Haemagglutinin titers on d 21 were greater (P = 0.054) in PC, and at d 28
      the haemagglutinin titers were quadratically affected in pigs fed PP (P = 0.070).
      There was a trend toward a decrease in crypt depth (P = 0.068) and a greater
      villus height:crypt depth ratio (P = 0.082) of ileum in PC compared with PP.
      These results suggest that PP may be an alternative to medicated feed with
      antibiotics because it showed antimicrobial activity by effectively reducing the
      population of coliform bacteria and also improved the performance of weanling
      pigs.

PMID- 18344304
TI  - Evaluation of the fermentation dynamics of soluble crude protein from three
      protein sources in continuous culture fermenters.
AB  - Eight dual-flow continuous culture fermenters (1.03 +/- 0.05 L) were used to
      assess differences in microbial degradation of the soluble CP fraction of canola
      meal (CMSCP), soybean meal (SBMSCP), and fish meal (FMSCP) using a completely
      randomized design with two 9-d experimental periods and a solution of tryptone as
      a control treatment (control). All fermenters received the same basal diet (58%
      ground corn, 40% canary grass hay, 0.4% vitamin-mineral premix, 1% CaCO(3), 0.6%
      salt on a DM basis) in 8 equal portions daily. During sampling on the last 3 d of
      each period, 90-mL doses containing soluble CP were infused into the fermenters
      30 min after the beginning of the first and last feedings of the day. The total
      amount of soluble CP supplied by the infusions of FMSCP, CMSCP, and SBMSCP was
      3.2 g/d, representing 24% of the daily dietary CP intake. Infusion of FMSCP
      resulted in the greatest (P < 0.05) NH(3)-N concentration (4.6 +/- 0.40 mg/dL)
      compared with the other treatments (0.5 +/- 0.40 mg/dL). Microbial N flow (g/d)
      from the fermenters was also greatest (P < 0.05) with FMSCP (1.42 +/- 0.062)
      compared with the other soluble CP fractions (1.08 +/- 0.062). The efficiency of
      microbial protein synthesis tended to be lowest with the control diet, and the
      efficiency of N utilization was lowest with FMSCP treatment. These results
      indicate that N was limiting microbial growth in the control diet, and there was
      more rumen-available N with the FMSCP diet compared with the other dietary
      treatments. The extent of degradation of the soluble CP fraction from fish meal,
      soybean meal, and canola meal was determined to be 99, 30, and 37% of soluble CP,
      respectively. These results indicate that the soluble CP fraction is not 100%
      degraded in all feeds and that assuming a high degradation extent of the soluble
      CP fraction from soybean meal and canola meal may result in an underestimation of
      the supply of undegradable protein from these protein sources.

PMID- 18344305
TI  - Recovering value from beef carcasses classified as dark cutters by United States
      Department of Agriculture graders.
AB  - Effects of the dark-cutting condition were examined on commercially slaughtered
      beef carcass sides that were classified into groups exhibiting 1/3, 1/2, and full
      degrees of the dark-cutting (DEGDC) condition, as evaluated by a USDA
      Agricultural Marketing Service grader (n = 20 per group). Twenty-nine muscles of
      each carcass side were evaluated to determine the ultimate pH and color (L*, a*,
      and b*). Fourteen beef muscles (biceps femoris, deep pectoral, chuck complexus,
      gluteus medius, infraspinatus, latissimus dorsi, psoas major, longissimus
      thoracis, longissimus lumborum, semimembranosus, semitendinosus, triceps brachii
      long head, tensor fasciae latae, and vastus lateralis) were evaluated using
      Warner-Bratzler Shear force (WBSF) and a trained sensory panel. The muscle x
      DEGDC interaction was significant for ultimate pH, L*, a*, and b* values (P <
      0.05). When ultimate pH values of individual muscles were compared with the same
      muscles evaluated in a previous study, the 1/3, 1/2, and full DEGDC had 7, 9, and
      5 muscles, respectively, that fell within a computed 95% prediction limit of what
      would be considered as a normal pH but were more variable as measured by within
      class CV. Color values (L*, a*, and b*) of the muscles from dark-cutting
      carcasses were numerically lower than those from the normal carcasses. A survey
      designed to determine the ideal color range of beef lean for retail meat
      merchandisers (n = 34) and food service chefs (n = 33) across the United States
      resulted in data analyzed using principal components analysis of L*, a*, and b*
      values for muscles dissected in the study to estimate the true values for dark
      cutting carcasses. Muscles that were within an acceptable color value range for
      food service chefs had the potential to add between $42.29 to $26.44 and $14.71
      to $8.11 per side when valued at Choice and Select prices, respectively. Muscles
      that were within an acceptable color value range had the potential to add between
      $30.39 to $16.74 and $10.37 to $5.03 per side for retail meat merchandisers when
      acceptable muscles were valued at Choice and Select prices, respectively. No
      muscle x DEGDC interactions were detected for WBSF and sensory panel scores (P >
      0.05), but differences were detected among muscles (P < 0.05). Several muscles
      were considered salvageable from the dark-cutting carcasses that were evaluated,
      and no significant differences in sensory scores or WBSF between DEGDC classes
      suggested equal sensory expectations for muscles from dark-cutting carcasses.

PMID- 18344306
TI  - Mitochondrial genome polymorphisms associated with longissimus muscle composition
      in Iberian pigs.
AB  - We carried out a study to investigate the associations between mitochondrial DNA
      polymorphisms and meat quality traits (intramuscular fat and protein content of
      the longissimus) in an Iberian porcine line named Torbiscal. The studied pigs (n
      = 319) belong to 9 maternal lineages and were previously assigned to 6
      mitochondrial haplotypes (H1 to H6), based on Cytochrome b and Dloop sequences.
      Statistical analyses, following a bivariate mixed model, show a greater fat
      content and lower protein content in H3 haplotype carriers than H1, H2, H4, H5,
      and H6 haplotype carriers. The magnitudes of these differences are close to 1 g
      of fat and -0.5 g of protein per 100 g of muscle. To identify the causative
      mutation of these effects on intramuscular fat and protein contents, the complete
      mitochondrial DNA sequence of 6 individuals was determined, each one carrying a
      different mitochondrial haplotype. The alignments of these 6 complete
      mitochondrial sequences allowed identification of 32 substitutions and 2 indels.
      Two polymorphic positions were exclusively detected in H3 carriers: a synonymous
      transition 9104C > T in the gene-coding region of Cytochrome c oxidase subunit
      III and a substitution 715A > G in 12S rRNA. Genotyping results of a larger
      number of Torbiscal samples showed the exclusive presence of 9104T and 715G
      alleles in H3 carriers. The detected candidate substitutions are located in
      essential mitochondrial genes, and although they do not change the amino acid
      composition, we cannot disregard a potential change in the secondary structure of
      their corresponding mRNA. The usefulness of these polymorphisms as markers in
      selection programs requires validation of the consistency of these results in
      other Iberian pig lines.

PMID- 18344307
TI  - Effect of dried corn distillers grains plus solubles compared with soybean hulls,
      in late gestation heifer diets, on animal and reproductive performance.
AB  - Dried distillers grains plus solubles (DDGS) contain fat and rumen undegradable
      intake protein, both of which have been shown to increase reproductive
      performance in heifers. The mechanisms leading to enhanced reproduction have not
      been fully defined. The objectives of this research were to evaluate effects of
      DDGS in late gestation heifer diets on animal and reproductive performance and on
      blood plasma concentrations of GH, IGF-I, and NEFA. Over 2 yr, 201 heifers were
      randomly allotted to 1 of 2 diets, which were similar in energy and adequate in
      rumen degradable intake protein and were fed from d 190 of gestation through
      calving. Diets were grass hay with DDGS or soybean hulls (SBH) and a supplement.
      Cow BW and BCS were measured from the beginning of treatment through weaning.
      Blood samples were collected prepartum on d 71 and 69 of the feeding period and
      weekly after calving for 4 and 6 wk (d 84 to 105 and d 76 to 111 relative to the
      feeding period) during yr 1 and 2, respectively. No treatment x year interactions
      were detected for any of the performance, hormonal, or reproductive dependent
      variables. Both treatments caused positive BW changes over the feeding period,
      but DDGS heifers had a greater (P < 0.01) positive BW change compared with SBH
      heifers. Initial and final BCS and BCS change were similar (P >/= 0.26) between
      DDGS and SBH treatments. Treatment did not influence (P >/= 0.12) BW or BCS
      change during the postpartum period. Calving ease, calf vigor, and calf birth
      weight, weaning weight, and ADG (birth to weaning) were similar (P >/= 0.41)
      between treatments. The proportion of cows that had initiated estrous cycles (P =
      0.46) and the pregnancy distribution (P >/= 0.21) were similar between
      treatments. However, a greater (P = 0.058) percentage of DDGS cows became
      pregnant compared with SBH cows (94 and 84%). In both years, there were no
      effects of treatment (P >/= 0.17) or treatment x time (P >/= 0.52), but time
      influenced (P </= 0.05) the concentrations of GH, IGF-I, and NEFA. Concentrations
      of GH were greater (P </= 0.05) at calving and decreased through d 4 after
      calving. The IGF-I concentrations were greater (P < 0.01) around calving and
      decreased (P < 0.05) through d 8 or 6 (yr 1 or 2) and remained similar (P > 0.10)
      for the duration of the sampling period. Concentrations of NEFA increased from
      calving through d 8 and gradually declined through d 20. Prepartum diets
      containing DDGS, a source of fat and UIP, benefited pregnancy rates in well
      maintained, primiparous beef heifers.

PMID- 18344308
TI  - Effects of temperature stress on growth performance and bacon quality in grow
      finish pigs housed at two densities.
AB  - Managing stressors is essential for optimizing pig growth performance. To
      determine the effects of temperature and space allocation on growth performance
      and carcass characteristics, pigs were housed within their thermoneutral zone, at
      23.9 degrees C, or above their thermoneutral zone, at 32.2 degrees C, and were
      provided either 0.66 or 0.93 m(2)/pig for the final 35 d of the grow-finish
      period. Individual BW were recorded on d 1, 10, 20, and 30. At slaughter, carcass
      measurements and samples of backfat and belly fat were collected. Final BW was
      decreased (P < or = 0.05) from 113 to 103 kg for pigs housed at 32.2 degrees C.
      The ADG was reduced (P < 0.05) for pigs housed at 32.2 degrees C (0.89 vs. 0.54
      kg/d), as was G:F (0.28 vs. 0.24). Housing at 0.66 m(2)/pig resulted in pigs that
      were lighter (P < or = 0.05), at 106 compared with 110 kg, as a result of
      decreased (P < or = 0.05) ADG (0.78 to 0.65 kg/d) and decreased (P < or = 0.05)
      G:F (0.275 to 0.255) compared with pigs housed at 0.93 m(2)/pig. Pigs housed at a
      greater spatial allocation had elevated (P < or = 0.05) ADFI. The interaction of
      housing at 32.2 degrees C and decreasing spatial allocation increased (P < or =
      0.05) the adipose iodine value from 66.8 to 70.4, decreased (P < or = 0.05) the
      saturated:unsaturated fatty acids ratio from 0.59 to 0.56, and increased (P < or
      = 0.05) the n-6:n-3 from 23.56 to 25.27. Decreased spatial allocation resulted in
      decreased (P < or = 0.05) belly weights. Although increased temperature did not
      affect belly weight, the 32.2 degrees C pigs had decreased (P < or = 0.05) raw
      and cooked slice weights, increased (P < or = 0.05) percentage lean of bacon,
      increased (P < or = 0.05) lean:fat ratio of bacon slices, increased (P < or =
      0.05) raw slice scores, and increased (P < or = 0.05) quantity of collagen in
      belly fat. Some of these changes may have resulted from changes in lipid
      metabolism. Increasing spatial allocation in the 32.2 degrees C pigs decreased
      fatty acid synthase (P = 0.03) and stearoyl-CoA desaturase- 1 (P = 0.08) mRNA
      expression in adipose tissue. The results from this study demonstrated decreased
      growth, carcass lipid quality, and bacon quality in pigs housed at temperatures
      above the thermoneutral zone; however, increasing the spatial allocation for
      housing may be a means to ameliorate the negative effects of temperature stress.

PMID- 18344309
TI  - Genetic relationship and diversity analysis of Indian water buffalo (Bubalus
      bubalis).
AB  - The water buffalo (Bubalus bubalis) is an important dairy animal on the Indian
      subcontinent and in Southeast Asian countries. The diversity and differentiation
      among 12 populations or breeds of buffalo were studied. Data were generated and
      analyzed from 527 animals belonging to 10 recognized breeds and 2 additional
      populations of Indian buffalo by using 22 microsatellite loci. Relationships
      among buffalo breeds and populations were estimated based on genetic distances.
      The Bayesian analysis grouped 12 populations into 8 distinctive clusters.
      Geographically close breeds clustered together, except for the Jaffarabadi and
      Murrah, which were not in geographic contiguity. The Mantel test revealed
      nonsignificant correlations between genetic and geographic distances. This
      supports the hypothesis that buffaloes have been domesticated at different places
      for specific purposes. The phylogenetic relationship based on microsatellite loci
      supported the breed classification based on body size. The Toda breed, which is
      considered to be endangered, had genotypes similar to those of the surrounding
      buffalo populations.

PMID- 18344310
TI  - Behavioral aspects of electronic bull separation and mate allocation in multiple
      sire mating paddocks.
AB  - Controlling spatial positioning of cattle through use of electronic collars could
      provide new ways to farm under extensive conditions. This study examined the
      potential for bulls to be controlled during mating using mild electric shocks
      delivered through radio-controlled collars. Eighteen Belmont Red bulls were
      fitted with collars containing the Global Positioning System and that were able
      to emit a mild electric shock (500 mW) at the top of the neck behind the poll.
      Eighteen Belmont Red cows were fitted with Global Positioning System collars
      only. The experiment was replicated 3 times in 3 paddocks. Each paddock contained
      2 bulls and 1 cow in induced estrus. On d 1, the bulls were either assigned to
      the cow or not assigned to the cow, and on d 2, the assignments were reversed,
      and bulls received the other treatment using a new cow. Treatments were applied
      for 2 h on each day. The nonassigned bull received a mild electric shock on
      approach to either the cow or to a bull, whereas the assigned bull received a
      mild electric shock on approach to the other bull only. The electric shock was
      applied when the bulls were within approximately 10 m and moving toward the
      nonallowed animal. The electric shock was terminated when the animal responded by
      stopping movement toward the nonallowed animal. In the first 10 min, nonassigned
      bulls spent less time within 5 m of the cow (P = 0.03) than assigned bulls.
      Assigned bulls spent more time close to the cow during the entire 120 min on d 1
      than on d 2 (P = 0.014). On d 1, the assigned bulls moved more toward the cow and
      the nonassigned bull than they did on d 2 (P = 0.02). Assigned bulls displayed
      more sexual behaviors than nonassigned bulls (P = 0.004). Nonassigned bulls were
      sometimes observed not to approach the cow despite a change in its location. This
      suggests that the bull associated the electric shock with the cow and not with
      the location in which it received the electric shock. Instances were observed in
      which the cow pursued the nonassigned bull, in which case the bull did not
      receive an electric shock, and this may reflect the preference of the cow. This
      study demonstrated that bulls can be separated and prevented from approaching a
      cow in estrus using a mild electric shock. However, mate allocation was not
      completely successful due to the potential for cow preference for certain bulls.

PMID- 18344311
TI  - Effects of oral administration of sodium citrate or acetate to pigs on blood
      parameters, postmortem glycolysis, muscle pH decline, and quality attributes of
      pork.
AB  - The objective of this study was to determine the effects of oral administration
      of sodium citrate (CIT) or acetate (ACE) to pigs on blood parameters, postmortem
      glycolysis, pH decline, and quality attributes of pork. Previous studies have
      shown that CIT has the potential to inhibit phosphofructokinase (PFK), a key
      enzyme in postmortem muscle glycolysis. In Exp. 1, CIT, ACE, or water was orally
      administered (0.75 g/kg of BW) to 24 pigs. After a 30-min rest, pigs were
      exercised, and blood samples were taken at 45 and 75 min after oral treatment.
      Citrate and ACE tended (P = 0.08) to increase blood pH and increased (P = 0.02)
      bicarbonate levels immediately after exercise. After a 30-min rest, blood pH of
      pigs administered ACE tended (P = 0.09) to remain higher, whereas blood pH of CIT
      treated pigs was similar to that of control pigs. Bicarbonate levels in ACE- and
      CIT-treated pigs were still greater (P < 0.05) than those of control pigs at 75
      min after oral treatment. In Exp. 2, 30 pigs were administered CIT, ACE, or water
      45 min before stunning (electric plus captive bolt). Antemortem treatments had no
      effect (P > 0.10) on muscle pH or postmortem concentrations of the glycolytic
      metabolites of glucose-6 phosphate, fructose-6 phosphate, fructose-1,6
      bisphosphate, glyceraldehyde-3 phosphate, dihydroxyacetone phosphate, or lactate.
      Minor, but inconsistent, differences in quality attributes were found in LM
      chops, and no differences in quality attributes were found between control and
      CIT- or ACE-treated pigs for inside and outside semimembranosus muscles (P >
      0.10). There was no significant inhibition of the PFK enzyme by orally
      administered CIT or ACE; however, the PFK glycolytic metabolite data analysis
      indicated that PFK was a main regulatory enzyme in postmortem muscle.

PMID- 18344312
TI  - The effect of dietary phosphorus and calcium level, phytase supplementation, and
      ileal infusion of pectin on the chemical composition and carbohydrase activity of
      fecal bacteria and the level of microbial metabolites in the gastrointestinal
      tract of pigs.
AB  - Two experiments with growing pigs were conducted to determine the effects of
      dietary P and Ca level, phytase supplementation, and ileal pectin infusion on
      ileal and fecal P and Ca balance, chemical composition of fecal mixed bacterial
      mass (MBM), and bacterial metabolic activity. Pigs (initial BW = 30 kg) were
      fitted with simple T-cannulas at the distal ileum. They were fed a low-P corn
      soybean meal control diet (3 g of P/kg) or the control diet supplemented with
      monocalcium phosphate (MCP; 7 g of P/kg; Exp. 1) or 1,000 FTU phytase/kg (Exp.
      2). The daily infusion treatments consisted of 60 g of pectin dissolved in 1.8 L
      of demineralized water or 1.8 L of demineralized water as the control infusion,
      infused via the ileal cannula. In each experiment, 8 barrows were assigned to 4
      dietary treatments according to a double, incomplete 4 x 2 Latin square. The
      dietary treatments in Exp. 1 were the control (Con-) diet with water infusion;
      the control (Con+) diet with pectin infusion; the MCP diet with water infusion;
      and the MCP diet with pectin infusion. In Exp. 2, the pigs received the same Con-
      and Con+ treatments as in Exp. 1 and, in addition, the phytase-supplemented diet
      in combination with water or pectin infusion. After a 15-d adaptation period,
      feces were collected for 5 d followed by ileal digesta collection for 24 h. In
      Exp. 1, supplemental MCP increased (P </= 0.003) ileal and fecal P and Ca
      recovery as well as P and Ca content of the MBM. Pectin infusion increased the N
      content of the MBM (P = 0.054) and polygalacturonase activity (P = 0.032) in
      feces. In addition, pectin decreased (P = 0.049) ileal and tended (P < 0. 079) to
      increase fecal VFA concentrations. In Exp. 2, phytase decreased ileal and fecal P
      recovery (P < 0.001) and the P content of the MBM (P = 0.045), whereas the N
      content of the MBM (P = 0.094) and fecal cellulase activity (P = 0.089) tended to
      decrease. Similarly, pectin infusion decreased (P = 0.036) fecal cellulase
      activity but increased (P < 0.001) polygalacturonase activity. In conclusion,
      these data indicate that bacterial P and Ca assimilation and metabolic activity
      depend on P and Ca availability in the large intestine and on the availability of
      fermentable substrate, such as pectin. Thus, increasing dietary P and Ca levels
      increases bacterial P and Ca assimilation due to greater intestinal P and Ca
      availability, whereas decreasing intestinal P availability for bacteria through
      phytase addition to low-P diets reduces bacterial P incorporation and seems to
      decrease bacterial activity.

PMID- 18344313
TI  - Influence of direct-fed fibrolytic enzymes on diet digestibility and ruminal
      activity in sheep fed a grass hay-based diet.
AB  - Six rumen-fistulated Merino sheep were used in a crossover design experiment to
      evaluate the effects of an exogenous fibrolytic enzyme preparation (12 g/d; ENZ),
      delivered directly into the rumen, on diet digestibility, ruminal fermentation,
      and microbial protein synthesis. The enzyme contained endoglucanase and xylanase
      activities. Sheep were fed a mixed grass hay:concentrate (70:30; DM basis) diet
      at a daily rate of 46.1 g/kg of BW(0.75). Samples of grass hay were incubated in
      situ in the rumen of each sheep to measure DM and NDF degradation. The
      supplementation with ENZ did not affect diet digestibility (P = 0.30 to 0.66),
      urinary excretion of purine derivatives (P = 0.34), ruminal pH (P = 0.46), or
      concentrations of NH(3)-N (P = 0.69) and total VFA (P = 0.97). In contrast, molar
      proportion of propionate were greater (P = 0.001) and acetate:propionate ratio
      was lower (P < 0.001) in ENZ-supplemented sheep. In addition, ENZ supplementation
      tended to increase (P = 0.06) numbers of cellulolytic bacteria at 4 h after
      feeding. Both the ruminally insoluble potentially degradable fraction of grass
      hay DM and its fractional rate of degradation were increased (P = 0.002 and 0.05,
      respectively) by ENZ treatment. Supplementation with ENZ also increased (P = 0.01
      to 0.02) effective and potential degradability of grass hay DM and NDF. Ruminal
      fluid endoglucanase and xylanase activities were greater (P < 0.001 and 0.03,
      respectively) in ENZ-supplemented sheep than in control animals. It was found
      that ENZ supplementation did not affect either exoglucanase (P = 0.12) or amylase
      (P = 0.83) activity. The results indicate that supplementing ENZ directly into
      the rumen increased the fibrolytic activity and stimulated the growth of
      cellulolytic bacteria without a prefeeding feed-enzyme interaction.

PMID- 18344314
TI  - Critical control points in the impact of the proinflammatory immune response on
      growth and metabolism.
AB  - Intrinsic in the equation for successful animal production is the efficiency of
      nutrient use for assimilation into useful animal-derived products. However, when
      young growing animals encounter various stressors that activate the
      proinflammatory response (PR), the biochemical effects of the resulting cascade
      of PR mediators [cytokines, prostaglandin and prosta-cyclin derivatives, nitric
      oxide (NO), superoxide anion (O2(.-)), etc.] override the regulatory signals
      normally ascribed to anabolic tissue accretion and growth. The efficiency of
      energy and nutrient use will proportionally decrease for growth rate due to the
      redirection of nutrient use to support immune defense processes. These
      proinflammatory events can develop in association with infectious disease but
      also are apparent in and a part of the natural response to birth, parturition,
      and weaning. If growth patterns are tracked during the PR, growth deficits are
      often apparent. Some growth deficits are relatively transient in duration,
      whereas others are quite long lasting, persisting although traditional clinical
      markers of PR are no longer evident. Recent evidence indicates that the PR
      cascades initiated by cytokines like tumor necrosis factor-alpha play a major
      role in these growth deficits. Perturbations in mitochondrial energetics and NO
      and O2(.-) interactions further affect metabolic balance. Free radicals and
      reactive nitrogen intermediates interact with select molecular targets in
      proteins (i.e., enzymes, histone proteins, and signal transduction proteins),
      causing the nitration and nitrosylation of select amino acids. If these
      posttranslational modifications occur in proteins associated with control points
      critical in metabolic stability, the resulting altered protein structure blocks
      its functionality. Attenuation of these overt posttranslational protein
      modifications at their site of production offers a strategy to minimize their
      detrimental impact while preserving needed cytokine, NO, and O2(.-) functions.

PMID- 18344315
TI  - Amiloride derivatives and a nonpeptidic antagonist bind at two distinct
      allosteric sites in the human gonadotropin-releasing hormone receptor.
AB  - The interest in the allosteric modulation of G protein-coupled receptors has
      grown during the past decade. It has been shown that ligands acting at allosteric
      sites present in these important drug targets have the ability to modulate
      receptor conformations and fine-tune pharmacological responses to the orthosteric
      ligand. In the present study, allosteric modulation of the human gonadotropin
      releasing hormone (GnRH) receptor by amiloride analogs [e.g., 5-(N,N
      hexamethylene)amiloride (HMA)] and a nonpeptide antagonistic furan derivative (FD
      1) was studied. First, the compounds' ability to influence the dissociation of a
      radiolabeled peptide agonist ((125)I-triptorelin) from human GnRH receptors
      stably expressed in Chinese hamster ovary cell membranes was investigated. HMA
      and FD-1, but not 5-(N-benzyl-N-methylaminomethyl)1-(2,6-difluorobenzyl)-6-[4-(3
      methoxyureido)phenyl]-3-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (TAK-013),
      another nonpeptide antagonist, were shown to increase the dissociation rate of
      (125)I-triptorelin, revealing their allosteric inhibitory characteristics. The
      simultaneous addition of HMA and FD-1 resulted in an additive effect on the
      dissociation rate. Second, in a functional assay, it was shown that HMA was a
      noncompetitive antagonist and that FD-1 had both competitive and noncompetitive
      antagonistic properties. Equilibrium displacement studies showed that the
      inhibition of (125)I-triptorelin binding by FD-1 was not affected by HMA.
      Furthermore, the potency of HMA to increase radioligand dissociation was not
      affected by the presence of FD-1. Simulation of the data obtained in the latter
      experiment also indicated neutral cooperativity between the binding of HMA and FD
      1. Taken together, these results demonstrate that HMA and FD-1 are allosteric
      inhibitors that bind at two distinct, noncooperative, allosteric sites. This
      presence of a second allosteric site may provide yet another opportunity for the
      discovery of new ligands for the human GnRH receptor.

PMID- 18344316
TI  - The Japanese guidelines for gastric cancer screening.
AB  - BACKGROUND: Gastric cancer is the leading cause of death from cancer in Japan. In
      2004, there were 50 562 deaths from gastric cancer; they accounted for 15.8% of
      the total number of cancer deaths. Since 1983, under the Health Service Law for
      the Aged, gastric cancer screening has been conducted nationwide for all
      residents aged 40 years and over. METHODS: On the basis of the standardized
      method developed for the Japanese Guidelines for Cancer Screening, the efficacies
      of various methods for gastric cancer screening were evaluated and the guideline
      was developed. RESULTS: Four methods for gastric cancer screening were evaluated:
      photofluorography, endoscopy, serum pepsinogen testing and Helicobacter pylori
      antibody testing. On the basis of the analytic framework involving key questions,
      1715 articles, published from January 1985 to February 2005, were selected using
      MEDLINE, the Japanese Medical Research Database and other methods. After the
      systematic literature review, 10 articles were identified as direct evidence and
      49 articles as indirect evidence. The studies that evaluated mortality reduction
      from gastric cancer included five case-control and two cohort studies for
      radiographic screening. On the basis of the balance of benefits and harms, the
      recommendations for population-based and opportunistic screening were formulated.
      Gastric cancer screening using photofluorography was recommended for both
      screening programs. The other methods were not recommended for population-based
      screening due to insufficient evidence. CONCLUSIONS: The guideline for gastric
      cancer screening guideline was developed based on the previously established
      method. Gastric cancer screening using photofluorography is recommended for
      population-based and opportunistic screening in Japan.

PMID- 18344317
TI  - Application of a walking suitability assessment to the immediate built
      environment surrounding elementary schools.
AB  - This study examines the usefulness of applying a walking suitability assessment
      to a specific geographic area surrounding elementary schools. Streets within a
      0.25-mile radius were measured to create a summary walking suitability score for
      seven schools from high-busing strata and seven from low-busing strata. Summary
      walking suitability scores were calculated for each school. A Mann-Whitney U test
      was conducted to determine any differences in scores between the high- and low
      busing schools. The median walking suitability score was 3.7 (a good rating); the
      25th percentile score was 2.9 (very good), and the 75th was 22.3 (poor). No
      statistical differences existed between busing strata. Walking suitability is an
      important consideration when examining the feasibility of walk-to-school programs
      within school settings; however, it might not be the main factor limiting
      children's active commuting to school. Several aspects of the environment were
      captured that researchers, practitioners, school personnel, and transportation
      experts may deem useful.

PMID- 18344318
TI  - Implementation, outcomes, and lessons learned from a collaborative primary health
      care program to improve diabetes care among urban Latino populations.
AB  - A collaborative primary health care service demonstration program was conducted
      to improve diabetes care among limited English-proficient (LEP) Latino patients.
      The intervention provided a multilevel approach aimed at patients and health care
      providers: Community health workers (CHWs) were mobilized to offer diabetes
      education in Spanish to LEP Latino diabetes patients, and health professions
      students and providers were offered intensive Spanish language training and
      cultural competency workshops. Positive outcomes for patients included a
      significant decrease in HbA1c. Health care providers reported improved patient
      communication and greater appreciation for cultural influences on health.
      Collaborating institutions realized ongoing benefits from expansion of CHWs' role
      and incorporation of cultural and language classes into health professions
      students' and house officers' training programs. Lessons learned included the
      importance of working together at every stage to identify and provide for the
      CHWs' training and support needs and to link the program's intervention with
      evaluation of multilevel outcomes.

PMID- 18344319
TI  - Systems approach identifies an organic nitrogen-responsive gene network that is
      regulated by the master clock control gene CCA1.
AB  - Understanding how nutrients affect gene expression will help us to understand the
      mechanisms controlling plant growth and development as a function of nutrient
      availability. Nitrate has been shown to serve as a signal for the control of gene
      expression in Arabidopsis. There is also evidence, on a gene-by-gene basis, that
      downstream products of nitrogen (N) assimilation such as glutamate (Glu) or
      glutamine (Gln) might serve as signals of organic N status that in turn regulate
      gene expression. To identify genome-wide responses to such organic N signals,
      Arabidopsis seedlings were transiently treated with ammonium nitrate in the
      presence or absence of MSX, an inhibitor of glutamine synthetase, resulting in a
      block of Glu/Gln synthesis. Genes that responded to organic N were identified as
      those whose response to ammonium nitrate treatment was blocked in the presence of
      MSX. We showed that some genes previously identified to be regulated by nitrate
      are under the control of an organic N-metabolite. Using an integrated network
      model of molecular interactions, we uncovered a subnetwork regulated by organic N
      that included CCA1 and target genes involved in N-assimilation. We validated some
      of the predicted interactions and showed that regulation of the master clock
      control gene CCA1 by Glu or a Glu-derived metabolite in turn regulates the
      expression of key N-assimilatory genes. Phase response curve analysis shows that
      distinct N-metabolites can advance or delay the CCA1 phase. Regulation of CCA1 by
      organic N signals may represent a novel input mechanism for N-nutrients to affect
      plant circadian clock function.

PMID- 18344320
TI  - Immunization by a bacterial aerosol.
AB  - By manufacturing a single-particle system in two particulate forms (i.e.,
      micrometer size and nanometer size), we have designed a bacterial vaccine form
      that exhibits improved efficacy of immunization. Microstructural properties are
      adapted to alter dispersive and aerosol properties independently. Dried
      "nanomicroparticle" vaccines possess two axes of nanoscale dimensions and a third
      axis of micrometer dimension; the last one permits effective micrometer-like
      physical dispersion, and the former provides alignment of the principal
      nanodimension particle axes with the direction of airflow. Particles formed with
      this combination of nano- and micrometer-scale dimensions possess a greater
      ability to aerosolize than particles of standard spherical isotropic shape and of
      similar geometric diameter. Here, we demonstrate effective application of this
      biomaterial by using the live attenuated tuberculosis vaccine bacille Calmette
      Guerin (BCG). Prepared as a spray-dried nanomicroparticle aerosol, BCG vaccine
      exhibited high-efficiency delivery and peripheral lung targeting capacity from a
      low-cost and technically simple delivery system. Aerosol delivery of the BCG
      nanomicroparticle to normal guinea pigs subsequently challenged with virulent
      Mycobacterium tuberculosis significantly reduced bacterial burden and lung
      pathology both relative to untreated animals and to control animals immunized
      with the standard parenteral BCG.

PMID- 18344321
TI  - Dipole tensor-based atomic-resolution structure determination of a
      nanocrystalline protein by solid-state NMR.
AB  - Magic-angle spinning (MAS) solid-state NMR (SSNMR) techniques have emerged in
      recent years for solving complete structures of uniformly labeled proteins
      lacking macroscopic order. Strategies used thus far have relied primarily on
      semiquantitative distance restraints, analogous to the nuclear Overhauser effect
      (NOE) routinely used in solution NMR. Here, we present a complementary approach
      for using relative orientations of molecular fragments, determined from dipolar
      line shapes. Whereas SSNMR distance restraints typically have an uncertainty of
      approximately 1 A, the tensor-based experiments report on relative vector
      (pseudobond) angles with precision of a few degrees. By using 3D techniques of
      this type, vector angle (VEAN) restraints were determined for the majority of the
      56-residue B1 immunoglobulin binding domain of protein G [protein GB1 (a total of
      47 HN-HN, 49 HN-HC, and 12 HA-HB restraints)]. By using distance restraints alone
      in the structure calculations, the overall backbone root-mean-square deviation
      (bbRMSD) was 1.01 +/- 0.13 A (1.52 +/- 0.12 A for all heavy atoms), which
      improved to 0.49 +/- 0.05 A (1.19 +/- 0.07 A) on the addition of empirical
      chemical shift [torsion angle likelihood obtained from shift and sequence
      similarity (TALOS)] restraints. VEAN restraints further improved the ensemble to
      0.31 +/- 0.06 A bbRMSD (1.06 +/- 0.07 A); relative to the structure with
      distances alone, most of the improvement remained (bbRMSD 0.64 +/- 0.09 A; 1.29
      +/- 0.07 A) when TALOS restraints were removed before refinement. These results
      represent significant progress toward atomic-resolution protein structure
      determination by SSNMR, capabilities that can be applied to a large range of
      membrane proteins and fibrils, which are often not amenable to solution NMR or x
      ray crystallography.

PMID- 18344322
TI  - Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as
      an effective treatment for promyelocytic leukemia.
AB  - To enhance therapeutic efficacy and reduce adverse effects, practitioners of
      traditional Chinese medicine (TCM) prescribe a combination of plant
      species/minerals, called formulae, based on clinical experience. Nearly 100,000
      formulae have been recorded, but the working mechanisms of most remain unknown.
      In trying to address the possible beneficial effects of formulae with current
      biomedical approaches, we use Realgar-Indigo naturalis formula (RIF), which has
      been proven to be very effective in treating human acute promyelocytic leukemia
      (APL) as a model. The main components of RIF are realgar, Indigo naturalis, and
      Salvia miltiorrhiza, with tetraarsenic tetrasulfide (A), indirubin (I), and
      tanshinone IIA (T) as major active ingredients, respectively. Here, we report
      that the ATI combination yields synergy in the treatment of a murine APL model in
      vivo and in the induction of APL cell differentiation in vitro. ATI causes
      intensified ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic
      acid receptor alpha (RARalpha) oncoprotein, stronger reprogramming of myeloid
      differentiation regulators, and enhanced G(1)/G(0) arrest in APL cells through
      hitting multiple targets compared with the effects of mono- or biagents.
      Furthermore, ATI intensifies the expression of Aquaglyceroporin 9 and facilitates
      the transportation of A into APL cells, which in turn enhances A-mediated PML
      RARalpha degradation and therapeutic efficacy. Our data also indicate A as the
      principal component of the formula, whereas T and I serve as adjuvant
      ingredients. We therefore suggest that dissecting the mode of action of
      clinically effective formulae at the molecular, cellular, and organism levels may
      be a good strategy in exploring the value of traditional medicine.

PMID- 18344323
TI  - Rapid large-scale evolutionary divergence in morphology and performance
      associated with exploitation of a different dietary resource.
AB  - Although rapid adaptive changes in morphology on ecological time scales are now
      well documented in natural populations, the effects of such changes on whole
      organism performance capacity and the consequences on ecological dynamics at the
      population level are often unclear. Here we show how lizards have rapidly evolved
      differences in head morphology, bite strength, and digestive tract structure
      after experimental introduction into a novel environment. Despite the short time
      scale ( approximately 36 years) since this introduction, these changes in
      morphology and performance parallel those typically documented among species and
      even families of lizards in both the type and extent of their specialization.
      Moreover, these changes have occurred side-by-side with dramatic changes in
      population density and social structure, providing a compelling example of how
      the invasion of a novel habitat can evolutionarily drive multiple aspects of the
      phenotype.

PMID- 18344324
TI  - RXLR effector reservoir in two Phytophthora species is dominated by a single
      rapidly evolving superfamily with more than 700 members.
AB  - Pathogens secrete effector molecules that facilitate the infection of their
      hosts. A number of effectors identified in plant pathogenic Phytophthora species
      possess N-terminal motifs (RXLR-dEER) required for targeting these effectors into
      host cells. Here, we bioinformatically identify >370 candidate effector genes in
      each of the genomes of P. sojae and P. ramorum. A single superfamily, termed
      avirulence homolog (Avh) genes, accounts for most of the effectors. The Avh
      proteins show extensive sequence divergence but are all related and likely
      evolved from a common ancestor by rapid duplication and divergence. More than
      half of the Avh proteins contain conserved C-terminal motifs (termed W, Y, and L)
      that are usually arranged as a module that can be repeated up to eight times. The
      Avh genes belong to the most rapidly evolving part of the genome, and they are
      nearly always located at synteny breakpoints. The superfamily includes all
      experimentally identified oomycete effector and avirulence genes, and its rapid
      pace of evolution is consistent with a role for Avh proteins in interaction with
      plant hosts.

PMID- 18344325
TI  - Population genomics of the wild yeast Saccharomyces paradoxus: Quantifying the
      life cycle.
AB  - Most microbes have complex life cycles with multiple modes of reproduction that
      differ in their effects on DNA sequence variation. Population genomic analyses
      can therefore be used to estimate the relative frequencies of these different
      modes in nature. The life cycle of the wild yeast Saccharomyces paradoxus is
      complex, including clonal reproduction, outcrossing, and two different modes of
      inbreeding. To quantify these different aspects we analyzed DNA sequence
      variation in the third chromosome among 20 isolates from two populations.
      Measures of mutational and recombinational diversity were used to make two
      independent estimates of the population size. In an obligately sexual population
      these values should be approximately equal. Instead there is a discrepancy of
      about three orders of magnitude between our two estimates of population size,
      indicating that S. paradoxus goes through a sexual cycle approximately once in
      every 1,000 asexual generations. Chromosome III also contains the mating type
      locus (MAT), which is the most outbred part in the entire genome, and by
      comparing recombinational diversity as a function of distance from MAT we
      estimate the frequency of matings to be approximately 94% from within the same
      tetrad, 5% with a clonemate after switching the mating type, and 1% outcrossed.
      Our study illustrates the utility of population genomic data in quantifying life
      cycles.

PMID- 18344326
TI  - Making autoantibodies safe.

PMID- 18344327
TI  - Efficient production of L-ribose with a recombinant Escherichia coli biocatalyst.
AB  - A new synthetic platform with potential for the production of several rare
      sugars, with l-ribose as the model target, is described. The gene encoding the
      unique NAD-dependent mannitol-1-dehydrogenase (MDH) from Apium graveolens (garden
      celery) was synthetically constructed for optimal expression in Escherichia coli.
      This MDH enzyme catalyzes the interconversion of several polyols and their l
      sugar counterparts, including the conversion of ribitol to l-ribose. Expression
      of recombinant MDH in the active form was successfully achieved, and one-step
      purification was demonstrated. Using the created recombinant E. coli strain as a
      whole-cell catalyst, the synthetic utility was demonstrated for production of l
      ribose, and the system was improved using shaken flask experiments. It was
      determined that addition of 50 to 500 microM ZnCl(2) and addition of 5 g/liter
      glycerol both improved production. The final levels of conversion achieved were
      >70% at a concentration of 40 g/liter and >50% at a concentration of 100 g/liter.
      The best conditions determined were then scaled up to a 1-liter fermentation that
      resulted in 55% conversion of 100 g/liter ribitol in 72 h, for a volumetric
      productivity of 17.4 g liter(-1) day(-1). This system represents a significantly
      improved method for the large-scale production of l-ribose.

PMID- 18344328
TI  - Impact of vacuum cooling on Escherichia coli O157:H7 infiltration into lettuce
      tissue.
AB  - Vacuum cooling is a common practice in the California leafy green industry. This
      study addressed the impact of vacuum cooling on the infiltration of Escherichia
      coli O157:H7 into lettuce as part of the risk assessment responding to the E.
      coli O157:H7 outbreaks associated with leafy green produce from California.
      Vacuum cooling significantly increased the infiltration of E. coli O157:H7 into
      the lettuce tissue (2.65E+06 CFU/g) compared to the nonvacuumed condition
      (1.98E+05 CFU/g). A stringent surface sterilization and quadruple washing could
      not eliminate the internalized bacteria from lettuce. It appeared that vacuuming
      forcibly changed the structure of lettuce tissue such as the stomata, suggesting
      a possible mechanism of E. coli O157:H7 internalization. Vacuuming also caused a
      lower reduction rate of E. coli O157:H7 in stored lettuce leaves than that for
      the nonvacuumed condition.

PMID- 18344329
TI  - Metabolic engineering of Escherichia coli for L-tyrosine production by expression
      of genes coding for the chorismate mutase domain of the native chorismate mutase
      prephenate dehydratase and a cyclohexadienyl dehydrogenase from Zymomonas
      mobilis.
AB  - The expression of the feedback inhibition-insensitive enzyme cyclohexadienyl
      dehydrogenase (TyrC) from Zymomonas mobilis and the chorismate mutase domain from
      native chorismate mutase-prephenate dehydratase (PheA(CM)) from Escherichia coli
      was compared to the expression of native feedback inhibition-sensitive chorismate
      mutase-prephenate dehydrogenase (CM-TyrA(p)) with regard to the capacity to
      produce l-tyrosine in E. coli strains modified to increase the carbon flow to
      chorismate. Shake flask experiments showed that TyrC increased the yield of l
      tyrosine from glucose (Y(l-Tyr/Glc)) by 6.8-fold compared to the yield obtained
      with CM-TyrA(p). In bioreactor experiments, a strain expressing both TyrC and
      PheA(CM) produced 3 g/liter of l-tyrosine with a Y(l-Tyr/Glc) of 66 mg/g. These
      values are 46 and 48% higher than the values for a strain expressing only TyrC.
      The results show that the feedback inhibition-insensitive enzymes can be employed
      for strain development as part of a metabolic engineering strategy for l-tyrosine
      production.

PMID- 18344330
TI  - Isolation and identification of rhizoxin analogs from Pseudomonas fluorescens Pf
      5 by using a genomic mining strategy.
AB  - The products synthesized from a hybrid polyketide synthase/nonribosomal peptide
      synthetase gene cluster in the genome of Pseudomonas fluorescens Pf-5 were
      identified using a genomics-guided strategy involving insertional mutagenesis and
      subsequent metabolite profiling. Five analogs of rhizoxin, a 16-member macrolide
      with antifungal, phytotoxic, and antitumor activities, were produced by Pf-5, but
      not by a mutant with an insertion in the gene cluster. The five rhizoxin analogs,
      one of which had not been described previously, were differentially toxic to two
      agriculturally important plant pathogens, Botrytis cinerea and Phytophthora
      ramorum. The rhizoxin analogs also caused swelling of rice roots, a symptom
      characteristic of rhizoxin itself, but were less toxic to pea and cucumber roots.
      Of the rhizoxin analogs produced by Pf-5, the predominant compound, WF-1360 F,
      and the newly described compound 22Z-WF-1360 F were most toxic against the two
      plant pathogens and three plant species. These rhizoxin analogs were tested
      against a panel of human cancer lines, and they exhibited potent but nonselective
      cytotoxicity. This study highlights the value of the genomic sequence of the soil
      bacterium P. fluorescens Pf-5 in providing leads for the discovery of novel
      metabolites with significant biological properties.

PMID- 18344331
TI  - High-Level folate production in fermented foods by the B12 producer Lactobacillus
      reuteri JCM1112.
AB  - We observed that Lactobacillus reuteri JCM1112 produces B(12) and folate.
      However, the folate/B(12) mass ratio found was far below that desired for human
      consumption ( approximately 170:1). We used metabolic engineering applying
      genetic and physiological approaches to improve this ratio and developed a
      generic and natural process that significantly increases folate production.

PMID- 18344332
TI  - Archaea dominate the ammonia-oxidizing community in the rhizosphere of the
      freshwater macrophyte Littorella uniflora.
AB  - Archaeal and bacterial ammonia monooxygenase genes (amoA) had similar low
      relative abundances in freshwater sediment. In the rhizosphere of the submersed
      macrophyte Littorella uniflora, archaeal amoA was 500- to >8,000-fold enriched
      compared to bacterial amoA, suggesting that the enhanced nitrification activity
      observed in the rhizosphere was due to ammonia-oxidizing Archaea.

PMID- 18344333
TI  - Empirical evaluation of a new method for calculating signal-to-noise ratio for
      microarray data analysis.
AB  - Signal-to-noise-ratio (SNR) thresholds for microarray data analysis were
      experimentally determined with an oligonucleotide array that contained perfect
      match (PM) and mismatch (MM) probes based upon four genes from Shewanella
      oneidensis MR-1. A new SNR calculation, called the signal-to-both-standard
      deviations ratio (SSDR), was developed and evaluated, along with other two
      methods, the signal-to-standard-deviation ratio (SSR) and the signal-to
      background ratio (SBR). At a low stringency, the thresholds of the SSR, SBR, and
      SSDR were 2.5, 1.60, and 0.80 with an oligonucleotide and a PCR amplicon as
      target templates and 2.0, 1.60, and 0.70 with genomic DNAs as target templates.
      Slightly higher thresholds were obtained under high-stringency conditions. The
      thresholds of the SSR and SSDR decreased with an increase in the complexity of
      targets (e.g., target types) and the presence of background DNA and a decrease in
      the compositions of targets, while the SBR remained unchanged in all situations.
      The lowest percentage of false positives and false negatives was observed with
      the SSDR calculation method, suggesting that it may be a better SNR calculation
      for more accurate determination of SNR thresholds. Positive spots identified by
      SNR thresholds were verified by the Student t test, and consistent results were
      observed. This study provides general guidance for users to select appropriate
      SNR thresholds for different samples under different hybridization conditions.

PMID- 18344334
TI  - Identification and onion pathogenicity of Burkholderia cepacia complex isolates
      from the onion rhizosphere and onion field soil.
AB  - Burkholderia cepacia complex strains are genetically related but phenotypically
      diverse organisms that are important opportunistic pathogens in patients with
      cystic fibrosis (CF,) as well as pathogens of onion and banana, colonizers of the
      rhizospheres of many plant species, and common inhabitants of bulk soil.
      Genotypic identification and pathogenicity characterization were performed on B.
      cepacia complex isolates from the rhizosphere of onion and organic soils in
      Michigan. A total of 3,798 putative B. cepacia complex isolates were recovered on
      Pseudomonas cepacia azelaic acid tryptamine and trypan blue tetracycline
      semiselective media during the 2004 growing season from six commercial onion
      fields located in two counties in Michigan. Putative B. cepacia complex isolates
      were identified by hybridization to a 16S rRNA gene probe, followed by duplex PCR
      using primers targeted to the 16S rRNA gene and recA sequences and restriction
      fragment length polymorphism analysis of the recA sequence. A total of 1,290
      isolates, 980 rhizosphere and 310 soil isolates, were assigned to the species B.
      cepacia (160), B. cenocepacia (480), B. ambifaria (623), and B. pyrrocinia (27).
      The majority of isolates identified as B. cepacia (85%), B. cenocepacia (90%),
      and B. ambifaria (76%) were pathogenic in a detached onion bulb scale assay and
      caused symptoms of water soaking, maceration, and/or necrosis. A phylogenetic
      analysis of recA sequences from representative B. cepacia complex type and panel
      strains, along with isolates collected in this study, revealed that the B.
      cenocepacia isolates associated with onion grouped within the III-B lineage and
      that some strains were closely related to strain AU1054, which was isolated from
      a CF patient. This study revealed that multiple B. cepacia complex species
      colonize the onion rhizosphere and have the potential to cause sour skin rot
      disease of onion. In addition, the onion rhizosphere is a natural habitat and a
      potential environmental source of B. cenocepacia.

PMID- 18344335
TI  - Microbes enriched in seawater after addition of coral mucus.
AB  - We investigated which microbial taxa in coastal Red Sea water were stimulated by
      addition of mucus from the coral Fungia sp. Decreases in the concentration and
      C/N ratio of particulate organic material during short-term incubations (50 h)
      were paralleled by a steep rise in the number of Gammaproteobacteria,
      particularly Alteromonadaceae, followed by Vibrionaceae. Two almost identical
      genotypes affiliated with Alteromonas macleodii accounted for up to >85% of all
      Alteromonadaceae (45% of the total cells) in the mucus-amended enrichments but
      were rare in unamended control incubations and in ambient seawater. A. macleodii
      like bacteria might thus be important in the transfer of organic carbon from
      coral mucus to the pelagic microbial food webs of coral reefs.

PMID- 18344336
TI  - The R1 conjugative plasmid increases Escherichia coli biofilm formation through
      an envelope stress response.
AB  - Differential gene expression in biofilm cells suggests that adding the
      derepressed conjugative plasmid R1drd19 increases biofilm formation by affecting
      genes related to envelope stress (rseA and cpxAR), biofilm formation (bssR and
      cstA), energy production (glpDFK), acid resistance (gadABCEX and hdeABD), and
      cell motility (csgBEFG, yehCD, yadC, and yfcV); genes encoding outer membrane
      proteins (ompACF), phage shock proteins (pspABCDE), and cold shock proteins
      (cspACDEG); and phage-related genes. To investigate the link between the
      identified genes and biofilm formation upon the addition of R1drd19, 40 isogenic
      mutants were classified according to their different biofilm formation
      phenotypes. Cells with class I mutations (those in rseA, bssR, cpxA, and ompA)
      exhibited no difference from the wild-type strain in biofilm formation and no
      increase in biofilm formation upon the addition of R1drd19. Cells with class II
      mutations (those in gatC, yagI, ompC, cspA, pspD, pspB, ymgB, gadC, pspC, ymgA,
      slp, cpxP, cpxR, cstA, rseC, ompF, and yqjD) displayed increased biofilm
      formation compared to the wild-type strain but decreased biofilm formation upon
      the addition of R1drd19. Class III mutants showed increased biofilm formation
      compared to the wild-type strain and increased biofilm formation upon the
      addition of R1drd19. Cells with class IV mutations displayed increased biofilm
      formation compared to the wild-type strain but little difference upon the
      addition of R1drd19, and class V mutants exhibited no difference from the wild
      type strain but increased biofilm formation upon the addition of R1drd19.
      Therefore, proteins encoded by the genes corresponding to the class I mutant
      phenotype are involved in R1drd19-promoted biofilm formation, primarily through
      their impact on cell motility. We hypothesize that the pili formed upon the
      addition of the conjugative plasmid disrupt the membrane (induce ompA) and
      activate the two-component system CpxAR as well as the other envelope stress
      response system, RseA-sigma(E), both of which, along with BssR, play a key role
      in bacterial biofilm formation.

PMID- 18344337
TI  - Biogeographic and phylogenetic diversity of thermoacidophilic cyanidiales in
      Yellowstone National Park, Japan, and New Zealand.
AB  - Members of the rhodophytan order Cyanidiales are unique among phototrophs in
      their ability to live in extreme environments that combine low pH levels (
      approximately 0.2 to 4.0) and moderately high temperatures of 40 to 56 degrees C.
      These unicellular algae occur in far-flung volcanic areas throughout the earth.
      Three genera (Cyanidium, Galdieria, and Cyanidioschyzon) are recognized. The
      phylogenetic diversity of culture isolates of the Cyanidiales from habitats
      throughout Yellowstone National Park (YNP), three areas in Japan, and seven
      regions in New Zealand was examined by using the chloroplast RuBisCO large
      subunit gene (rbcL) and the 18S rRNA gene. Based on the nucleotide sequences of
      both genes, the YNP isolates fall into two groups, one with high identity to
      Galdieria sulphuraria (type II) and another that is by far the most common and
      extensively distributed Yellowstone type (type IA). The latter is a spherical,
      walled cell that reproduces by internal divisions, with a subsequent release of
      smaller daughter cells. This type, nevertheless, shows a 99 to 100% identity to
      Cyanidioschyzon merolae (type IB), which lacks a wall, divides by "fission"-like
      cytokinesis into two daughter cells, and has less than 5% of the cell volume of
      type IA. The evolutionary and taxonomic ramifications of this disparity are
      discussed. Although the 18S rRNA and rbcL genes did not reveal diversity among
      the numerous isolates of type IA, chloroplast short sequence repeats did show
      some variation by location within YNP. In contrast, Japanese and New Zealand
      strains showed considerable diversity when we examined only the sequences of 18S
      and rbcL genes. Most exhibited identities closer to Galdieria maxima than to
      other strains, but these identities were commonly as low as 91 to 93%. Some of
      these Japanese and New Zealand strains probably represent undescribed species
      that diverged after long-term geographic isolation.

PMID- 18344338
TI  - Ecological dynamics of the toxic bloom-forming cyanobacterium Microcystis
      aeruginosa and its cyanophages in freshwater.
AB  - The abundance of potentially Microcystis aeruginosa-infectious cyanophages in
      freshwater was studied using g91 real-time PCR. A clear increase in cyanophage
      abundance was observed when M. aeruginosa numbers declined, showing that these
      factors were significantly negatively correlated. Furthermore, our data suggested
      that cyanophage dynamics may also affect shifts in microcystin-producing and non
      microcystin-producing populations.

PMID- 18344339
TI  - Imaging of long-distance alpha-aminoisobutyric acid translocation dynamics during
      resource capture by Serpula lacrymans.
AB  - alpha-Aminoisobutyric acid (AIB) is a nonmetabolized amino acid analogue of
      alanine, which at low (muM) concentrations acts as a tracer for amino acid
      movements. At high concentrations (mM), it competitively inhibits membrane
      transport and metabolism of protein amino acids and acts as a systemic
      translocated inhibitor of mycelial extension in fungi. AIB can control mycelial
      spread of the basidiomycete Serpula lacrymans, the cause of brown rot of wood in
      buildings. However, it is not known how effectively the inhibitor is distributed
      throughout the mycelium. Realistically heterogeneous microcosms, in which the
      fungus grew across nutritionally inert sand to colonize discrete wood resources,
      were used to investigate patterns of inhibition and translocation following local
      application of AIB. At a 0.1 M concentration, locally applied AIB caused
      immediate arrest of extension throughout the whole mycelium, maintained for a 6
      week experimental period. The dynamics of translocation of subtoxic amounts of [1
      (14)C]AIB ([(14)C]AIB) were mapped by photon-counting scintillation imaging in
      conjunction with destructive harvest to establish the velocity, direction, and
      rate of translocation and the extent of [(14)C]AIB reallocation accompanying the
      invasion of fresh wood. Locally applied [(14)C]AIB was distributed throughout
      complex mycelial networks within 2 h of application, becoming localized in
      growing margins by 12 h. Encounter with a fresh wood resource triggered a
      widespread response, causing withdrawal of [(14)C]AIB from throughout the
      network, accompanied by accumulation in the newly colonized wood and associated
      mycelium. The results are discussed in the context of nutrient dynamics in wood
      decomposer fungi and the mechanism of the amino acid reallocation response.

PMID- 18344340
TI  - Malic acid production by Saccharomyces cerevisiae: engineering of pyruvate
      carboxylation, oxaloacetate reduction, and malate export.
AB  - Malic acid is a potential biomass-derivable "building block" for chemical
      synthesis. Since wild-type Saccharomyces cerevisiae strains produce only low
      levels of malate, metabolic engineering is required to achieve efficient malate
      production with this yeast. A promising pathway for malate production from
      glucose proceeds via carboxylation of pyruvate, followed by reduction of
      oxaloacetate to malate. This redox- and ATP-neutral, CO(2)-fixing pathway has a
      theoretical maximum yield of 2 mol malate (mol glucose)(-1). A previously
      engineered glucose-tolerant, C(2)-independent pyruvate decarboxylase-negative S.
      cerevisiae strain was used as the platform to evaluate the impact of individual
      and combined introduction of three genetic modifications: (i) overexpression of
      the native pyruvate carboxylase encoded by PYC2, (ii) high-level expression of an
      allele of the MDH3 gene, of which the encoded malate dehydrogenase was retargeted
      to the cytosol by deletion of the C-terminal peroxisomal targeting sequence, and
      (iii) functional expression of the Schizosaccharomyces pombe malate transporter
      gene SpMAE1. While single or double modifications improved malate production, the
      highest malate yields and titers were obtained with the simultaneous introduction
      of all three modifications. In glucose-grown batch cultures, the resulting
      engineered strain produced malate at titers of up to 59 g liter(-1) at a malate
      yield of 0.42 mol (mol glucose)(-1). Metabolic flux analysis showed that
      metabolite labeling patterns observed upon nuclear magnetic resonance analyses of
      cultures grown on (13)C-labeled glucose were consistent with the envisaged
      nonoxidative, fermentative pathway for malate production. The engineered strains
      still produced substantial amounts of pyruvate, indicating that the pathway
      efficiency can be further improved.

PMID- 18344341
TI  - Innovative methods for soil DNA purification tested in soils with widely
      differing characteristics.
AB  - Seven methods of soil DNA extraction and purification were tested in a set of 14
      soils differing in bedrock, texture, pH, salinity, moisture, organic matter
      content, and vegetation cover. The methods introduced in this study included
      pretreatment of soil with CaCO(3) or purification of extracted DNA by CaCl(2).
      The performance of innovated methods was compared to that of the commercial kit
      Mo Bio PowerSoil and the phenol-chloroform-based method of D. N. Miller, J. E.
      Bryant, E. L. Madsen, and W. C. Ghiorse (Appl. Environ. Microbiol. 65:4715-4724,
      1999). This study demonstrated significant differences between the tested methods
      in terms of DNA yield, PCR performance, and recovered bacterial diversity. The
      differences in DNA yields were correlated to vegetation cover, soil pH, and clay
      content. The differences in PCR performances were correlated to vegetation cover
      and soil pH. The innovative methods improved PCR performance in our set of soils,
      in particular for forest acidic soils. PCR was successful in 95% of cases by the
      method using CaCl(2) purification and in 93% of cases by the method based on
      CaCO(3) pretreatment, but only in 79% by Mo Bio PowerSoil, for our range of
      soils. Also, the innovative methods recovered a higher percentage of actinomycete
      diversity from a subset of three soils. Recommendations include the assessment of
      soil characteristics prior to selecting the optimal protocol for soil DNA
      extraction and purification.

PMID- 18344342
TI  - Identification of differentially regulated francisella tularensis genes by use of
      a newly developed Tn5-based transposon delivery system.
AB  - Francisella tularensis is the etiologic agent of an intracellular systemic
      infection of the lymphatic system in humans called tularemia. The organism has
      become the subject of considerable research interest due to its classification as
      a category A select agent by the CDC. To aid genetic analysis of this pathogen,
      we have constructed a temperature-sensitive Tn5-based transposon delivery system
      that is capable of generating chromosomal reporter fusions with lacZ or luxCDABE,
      enabling us to monitor gene expression. Transposition is catalyzed by the
      hyperactive Tn5 transposase, whose expression is driven by the Francisella groES
      promoter. When high-temperature selection (42 degrees C) is applied to a
      bacterial culture carrying the transposon delivery plasmid, approximately 0.1% of
      the population is recovered with Tn5 insertions in the chromosome. Nucleotide
      sequence analysis of a sample of mutants revealed that the insertions occur
      randomly throughout the chromosome. The kanamycin-selectable marker of the
      transposon is also flanked by FLP recombination target sequences that allow
      deletion of the antibiotic resistance gene when desired. This system has been
      used to generate transposon mutant libraries for the F. tularensis live vaccine
      strain as well as two different virulent F. tularensis strains. Chromosomal
      reporters delivered with the transposon were used to identify genes upregulated
      by growth in Chamberlain's defined medium. Genes in the fsl operon, reported to
      be involved in iron acquisition, as well as genes in the igl gene cluster were
      among those identified by the screen. Further experiments implicate the ferric
      uptake regulator (Fur) protein in the negative regulation of fsl but not igl
      reporters, which occurs in an iron-dependent manner. Our results indicate that we
      have created a valuable new transposon that can be used to identify and
      characterize virulence genes in F. tularensis strains.

PMID- 18344343
TI  - Effect of wastewater treatment plant effluent on microbial function and community
      structure in the sediment of a freshwater stream with variable seasonal flow.
AB  - We investigated the effects of wastewater treatment plant (WWTP) discharge on the
      ecology of bacterial communities in the sediment of a small, low-gradient stream
      in South Australia. The quantification of genes involved in the biogeochemical
      cycling of carbon and nitrogen was used to assess potential impacts on ecosystem
      functions. The effects of disturbance on bacterial community structure were
      assessed by PCR-denaturing gradient gel electrophoresis of 16S rRNA genes, and
      clone library analysis was used to phylogenetically characterize significant
      shifts. Significant (P < 0.05) shifts in bacterial community structures were
      associated with alteration of the sediment's physicochemical properties,
      particularly nutrient loading from the WWTP discharge. The effects were greatest
      at the sampling location 400 m downstream of the outfall where the stream flow is
      reduced. This highly affected stretch of sediment contained representatives of
      the gammaproteobacteria that were absent from less-disturbed sites, including
      Oceanospirillales and Methylococcaceae. 16S rRNA gene sequences from less
      disturbed sites had representatives of the Caulobacteraceae, Sphingomonadaceae,
      and Nitrospirae which were not represented in samples from disturbed sediment.
      The diversity was lowest at the reference site; it increased with proximity to
      the WWTP outfall and declined toward highly disturbed (400 m downstream) sites (P
      < 0.05). The potential for biological transformations of N varied significantly
      with the stream sediment location (P < 0.05). The abundance of amoA, narG, and
      nifH genes increased with the distance downstream of the outfall. These processes
      are driven by N and C availability, as well as redox conditions. Together these
      data suggest cause and effect between nutrient loading into the creek, shift in
      bacterial communities through habitat change, and alteration of capacity for
      biogeochemical cycling of N.

PMID- 18344344
TI  - Application of functional genomics to pathway optimization for increased
      isoprenoid production.
AB  - Producing complex chemicals using synthetic metabolic pathways in microbial hosts
      can have many advantages over chemical synthesis but is often complicated by
      deleterious interactions between pathway intermediates and the host cell
      metabolism. With the maturation of functional genomic analysis, it is now
      technically feasible to identify modes of toxicity associated with the
      accumulation of foreign molecules in the engineered bacterium. Previously,
      Escherichia coli was engineered to produce large quantities of isoprenoids by
      creating a mevalonate-based isopentenyl pyrophosphate biosynthetic pathway (V. J.
      J. Martin et al., Nat. Biotechnol. 21:796-802, 2003). The engineered E. coli
      strain produced high levels of isoprenoids, but further optimization led to an
      imbalance in carbon flux and the accumulation of the pathway intermediate 3
      hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA), which proved to be cytotoxic to E.
      coli. Using both DNA microarray analysis and targeted metabolite profiling, we
      have studied E. coli strains inhibited by the intracellular accumulation of HMG
      CoA. Our results indicate that HMG-CoA inhibits fatty acid biosynthesis in the
      microbial host, leading to generalized membrane stress. The cytotoxic effects of
      HMG-CoA accumulation can be counteracted by the addition of palmitic acid (16:0)
      and, to a lesser extent, oleic acid (cis-Delta(9)-18:1) in the growth medium.
      This work demonstrates the utility of using transcriptomic and metabolomic
      methods to optimize synthetic biological systems.

PMID- 18344345
TI  - Rapid differentiation of phenotypically similar yeast species by single-strand
      conformation polymorphism analysis of ribosomal DNA.
AB  - Single-strand conformation polymorphism (SSCP) analysis of ribosomal DNA (rDNA)
      was investigated for rapid differentiation of phenotypically similar yeast
      species. Sensitive tests indicated that some yeast strains with one, most strains
      with two, and all strains with three or more nucleotide differences in the
      internal transcribed spacer 1 (ITS1) or ITS2 region could be distinguished by PCR
      SSCP analysis. The discriminative power of SSCP in yeast species differentiation
      was demonstrated by comparative studies of representative groups of yeast species
      from ascomycetes and basidiomycetes, including Saccharomyces species, medically
      important Candida species, and phylloplane basidiomycetous yeast species. Though
      the species within each group selected are closely related and have relatively
      similar rDNA sequences, they were clearly differentiated by PCR-SSCP analysis of
      the ITS1 region, given the amplified fragments were less than 350 bp in sizes. By
      using SSCP analysis for rapid screening of yeast strains with different rDNA
      sequences, species diversity existing in a large collection of yeast strains from
      natural sources was effectively and thoroughly investigated with substantially
      reduced time and cost in subsequent DNA sequencing.

PMID- 18344346
TI  - Genomic insights into Mn(II) oxidation by the marine alphaproteobacterium
      Aurantimonas sp. strain SI85-9A1.
AB  - Microbial Mn(II) oxidation has important biogeochemical consequences in marine,
      freshwater, and terrestrial environments, but many aspects of the physiology and
      biochemistry of this process remain obscure. Here, we report genomic insights
      into Mn(II) oxidation by the marine alphaproteobacterium Aurantimonas sp. strain
      SI85-9A1, isolated from the oxic/anoxic interface of a stratified fjord. The SI85
      9A1 genome harbors the genetic potential for metabolic versatility, with genes
      for organoheterotrophy, methylotrophy, oxidation of sulfur and carbon monoxide,
      the ability to grow over a wide range of O(2) concentrations (including
      microaerobic conditions), and the complete Calvin cycle for carbon fixation.
      Although no growth could be detected under autotrophic conditions with Mn(II) as
      the sole electron donor, cultures of SI85-9A1 grown on glycerol are dramatically
      stimulated by addition of Mn(II), suggesting an energetic benefit from Mn(II)
      oxidation. A putative Mn(II) oxidase is encoded by duplicated multicopper oxidase
      genes that have a complex evolutionary history including multiple gene
      duplication, loss, and ancient horizontal transfer events. The Mn(II) oxidase was
      most abundant in the extracellular fraction, where it cooccurs with a putative
      hemolysin-type Ca(2+)-binding peroxidase. Regulatory elements governing the
      cellular response to Fe and Mn concentration were identified, and 39 targets of
      these regulators were detected. The putative Mn(II) oxidase genes were not among
      the predicted targets, indicating that regulation of Mn(II) oxidation is
      controlled by other factors yet to be identified. Overall, our results provide
      novel insights into the physiology and biochemistry of Mn(II) oxidation and
      reveal a genome specialized for life at the oxic/anoxic interface.

PMID- 18344347
TI  - Relative abundance of Bacteroides spp. in stools and wastewaters as determined by
      hierarchical oligonucleotide primer extension.
AB  - A molecular method, termed hierarchical oligonucleotide primer extension (HOPE),
      was used to determine the relative abundances of predominant Bacteroides spp.
      present in fecal microbiota and wastewaters. For this analysis, genomic DNA in
      feces of healthy human adults, bovines, and swine and in wastewaters was
      extracted and total bacterial 16S rRNA genes were PCR amplified and used as the
      DNA templates for HOPE. Nineteen oligonucleotide primers were designed to detect
      14 Bacteroides spp. at different hierarchical levels (domain, order, cluster, and
      species) and were arranged into and used in six multiplex HOPE reaction mixtures.
      Results showed that species like B. vulgatus, B. thetaiotaomicron, B. caccae, B.
      uniformis, B. fragilis, B. eggerthii, and B. massiliensis could be individually
      detected in human feces at abundances corresponding to as little as 0.1% of PCR
      amplified 16S rRNA genes. Minor species like B. pyogenes, B. salyersiae, and B.
      nordii were detected only collectively using a primer that targeted the B.
      fragilis subgroup (corresponding to approximately 0.2% of PCR-amplified 16S rRNA
      genes). Furthermore, Bac303-related targets (i.e., most Bacteroidales) were
      observed to account for 28 to 44% of PCR-amplified 16S rRNA genes from human
      fecal microbiota, and their abundances were higher than those detected in the
      bovine and swine fecal microbiota and in wastewaters by factors of five and two,
      respectively. These results were comparable to those obtained by quantitative PCR
      and to those reported previously from studies using whole-cell fluorescence
      hybridization and 16S rRNA clone library methods, supporting the conclusion that
      HOPE can be a sensitive, specific, and rapid method to determine the relative
      abundances of Bacteroides spp. predominant in fecal samples.

PMID- 18344348
TI  - Estimates of biogenic methane production rates in deep marine sediments at
      Hydrate Ridge, Cascadia margin.
AB  - Methane hydrate found in marine sediments is thought to contain gigaton
      quantities of methane and is considered an important potential fuel source and
      climate-forcing agent. Much of the methane in hydrates is biogenic, so models
      that predict the presence and distribution of hydrates require accurate rates of
      in situ methanogenesis. We estimated the in situ methanogenesis rates in Hydrate
      Ridge (HR) sediments by coupling experimentally derived minimal rates of
      methanogenesis to methanogen biomass determinations for discrete locations in the
      sediment column. When starved in a biomass recycle reactor, Methanoculleus
      submarinus produced ca. 0.017 fmol methane/cell/day. Quantitative PCR (QPCR)
      directed at the methyl coenzyme M reductase subunit A gene (mcrA) indicated that
      75% of the HR sediments analyzed contained <1,000 methanogens/g. The highest
      numbers of methanogens were found mostly from sediments <10 m below seafloor. By
      considering methanogenesis rates for starved methanogens (adjusted to account for
      in situ temperatures) and the numbers of methanogens at selected depths, we
      derived an upper estimate of <4.25 fmol methane produced/g sediment/day for the
      samples with fewer methanogens than the QPCR method could detect. The actual
      rates could vary depending on the real number of methanogens and various seafloor
      parameters that influence microbial activity. However, our calculated rate is
      lower than rates previously reported for such sediments and close to the rate
      derived using geochemical modeling of the sediments. These data will help to
      improve models that predict microbial gas generation in marine sediments and
      determine the potential influence of this source of methane on the global carbon
      cycle.

PMID- 18344349
TI  - Novel root fungal consortium associated with a dominant desert grass.
AB  - The broad distribution and high colonization rates of plant roots by a variety of
      endophytic fungi suggest that these symbionts have an important role in the
      function of ecosystems. Semiarid and arid lands cover more than one-third of the
      terrestrial ecosystems on Earth. However, a limited number of studies have been
      conducted to characterize root-associated fungal communities in semiarid
      grasslands. We conducted a study of the fungal community associated with the
      roots of a dominant grass, Bouteloua gracilis, at the Sevilleta National Wildlife
      Refuge in New Mexico. Internal transcribed spacer ribosomal DNA sequences from
      roots collected in May 2005, October 2005, and January 2006 were amplified using
      fungal-specific primers, and a total of 630 sequences were obtained, 69% of which
      were novel (less than 97% similarity with respect to sequences in the NCBI
      database). B. gracilis roots were colonized by at least 10 different orders,
      including endophytic, coprophilous, mycorrhizal, saprophytic, and plant
      pathogenic fungi. A total of 51 operational taxonomic units (OTUs) were found,
      and diversity estimators did not show saturation. Despite the high diversity
      found within B. gracilis roots, the root-associated fungal community is dominated
      by a novel group of dark septate fungi (DSF) within the order Pleosporales.
      Microscopic analysis confirmed that B. gracilis roots are highly colonized by
      DSF. Other common orders colonizing the roots included Sordariales, Xylariales,
      and Agaricales. By contributing to drought tolerance and nutrient acquisition,
      DSF may be integral to the function of arid ecosystems.

PMID- 18344350
TI  - Dynamics of the methanogenic archaeal community during plant residue
      decomposition in an anoxic rice field soil.
AB  - Incorporation of plant residues strongly enhances the methane production and
      emission from flooded rice fields. Temperature and residue type are important
      factors that regulate residue decomposition and CH(4) production. However, the
      response of the methanogenic archaeal community to these factors in rice field
      soil is not well understood. In the present experiment, the structure of the
      archaeal community was determined during the decomposition of rice root and straw
      residues in anoxic rice field soil incubated at three temperatures (15 degrees C,
      30 degrees C, and 45 degrees C). More CH(4) was produced in the straw treatment
      than root treatment. Increasing the temperature from 15 degrees C to 45 degrees C
      enhanced CH(4) production. Terminal restriction fragment length polymorphism
      analyses in combination with cloning and sequencing of 16S rRNA genes showed that
      Methanosarcinaceae developed early in the incubations, whereas Methanosaetaceae
      became more abundant in the later stages. Methanosarcinaceae and Methanosaetaceae
      seemed to be better adapted at 15 degrees C and 30 degrees C, respectively, while
      the thermophilic Methanobacteriales and rice cluster I methanogens were
      significantly enhanced at 45 degrees C. Straw residues promoted the growth of
      Methanosarcinaceae, whereas the root residues favored Methanosaetaceae. In
      conclusion, our study revealed a highly dynamic structure of the methanogenic
      archaeal community during plant residue decomposition. The in situ concentration
      of acetate (and possibly of H(2)) seems to be the key factor that regulates the
      shift of methanogenic community.

PMID- 18344351
TI  - Randomly amplified polymorphic DNA PCR as a tool for assessment of marine viral
      richness.
AB  - Recent discoveries have uncovered considerable genetic diversity among aquatic
      viruses and raised questions about the variability of this diversity within and
      between environments. Studies of the temporal and spatial dynamics of aquatic
      viral assemblages have been hindered by the lack of a common genetic marker among
      viruses for rapid diversity assessments. Randomly amplified polymorphic DNA
      (RAPD) PCR bypasses this obstacle by sampling at the genetic level without
      requiring viral isolation or previous sequence knowledge. In this study, the
      utility of RAPD-PCR for assessing DNA viral richness within Chesapeake Bay water
      samples was evaluated. RAPD-PCR using single 10-mer oligonucleotide primers
      successfully produced amplicons from a variety of viral samples, and banding
      patterns were highly reproducible, indicating that each band likely represents a
      single amplicon originating from viral template DNA. In agreement with
      observations from other community profiling techniques, resulting RAPD-PCR
      banding patterns revealed more temporal than spatial variability in Chesapeake
      Bay virioplankton assemblages. High-quality hybridization probes and sequence
      information were also easily generated from single RAPD-PCR products or whole
      reactions. Thus, the RAPD-PCR technique appears to be practical and efficient for
      routine use in high-resolution viral diversity studies by providing assemblage
      comparisons through fingerprinting, probing, or sequence information.

PMID- 18344352
TI  - Specific molecular recognition and nonspecific contributions to bacterial
      interaction forces.

PMID- 18344353
TI  - Impact of nitrate on the structure and function of bacterial biofilm communities
      in pipelines used for injection of seawater into oil fields.
AB  - We studied the impact of NO(3)(-) on the bacterial community composition,
      diversity, and function in in situ industrial, anaerobic biofilms by combining
      microsensor profiling, (15)N and (35)S labeling, and 16S rRNA gene-based
      fingerprinting. Biofilms were grown on carbon steel coupons within a system
      designed to treat seawater for injection into an oil field for pressurized oil
      recovery. NO(3)(-) was added to the seawater in an attempt to prevent bacterial
      H(2)S generation and microbially influenced corrosion in the field.
      Microprofiling of nitrogen compounds and redox potential inside the biofilms
      showed that the zone of highest metabolic activity was located close to the metal
      surface, correlating with a high bacterial abundance in this zone. Upon addition,
      NO(3)(-) was mainly reduced to NO(2)(-). In biofilms grown in the absence of
      NO(3)(-), redox potentials of <-450 mV at the metal surface suggested the release
      of Fe(2+). NO(3)(-) addition to previously untreated biofilms induced a decline
      (65%) in bacterial species richness, with Methylophaga- and Colwellia-related
      sequences having the highest number of obtained clones in the clone library. In
      contrast, no changes in community composition and potential NO(3)(-) reduction
      occurred upon subsequent withdrawal of NO(3)(-). Active sulfate reduction was
      below detection levels in all biofilms, but S isotope fractionation analysis of
      sulfide deposits suggested that it must have occurred either at low rates or
      episodically. Scanning electron microscopy revealed that pitting corrosion
      occurred on all coupons, independent of the treatment. However, uniform corrosion
      was clearly mitigated by NO(3)(-) addition.

PMID- 18344354
TI  - Early oxidative damage underlying neurodegeneration in X-adrenoleukodystrophy.
AB  - X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disorder,
      characterized by progressive cerebral demyelination cerebral childhood
      adrenoleukodystrophy (CCALD) or spinal cord neurodegeneration
      (adrenomyeloneuropathy, AMN), adrenal insufficiency and accumulation of very long
      chain fatty acids (VLCFA) in tissues. The disease is caused by mutations in the
      ABCD1 gene, which encodes a peroxisomal transporter that plays a role in the
      import of VLCFA or VLCFA-CoA into peroxisomes. The Abcd1 knockout mice develop a
      spinal cord disease that mimics AMN in adult patients, with late onset at 20
      months of age. The mechanisms underlying cerebral demyelination or axonal
      degeneration in spinal cord are unknown. Here, we present evidence by gas
      chromatography/mass spectrometry that malonaldehyde-lysine, a consequence of
      lipoxidative damage to proteins, accumulates in the spinal cord of Abcd1 knockout
      mice as early as 3.5 months of age. At 12 months, Abcd1- mice accumulate
      additional proteins modified by oxidative damage arising from metal-catalyzed
      oxidation and glycoxidation/lipoxidation. While we show that VLCFA excess
      activates enzymatic antioxidant defenses at the protein expression levels, both
      in neural tissue, in ex vivo organotypic spinal cord slices from Abcd1- mice, and
      in human ALD fibroblasts, we also demonstrate that the loss of Abcd1 gene
      function hampers oxidative stress homeostasis. We find that the alpha-tocopherol
      analog Trolox is able to reverse oxidative lesions in vitro, thus providing
      therapeutic hope. These results pave the way for the identification of
      therapeutic targets that could reverse the deregulated response to oxidative
      stress in X-ALD.

PMID- 18344355
TI  - Toxic effects of X-linked adrenoleukodystrophy-associated, very long chain fatty
      acids on glial cells and neurons from rat hippocampus in culture.
AB  - Saturated very long chain fatty acids (VLCFAs; > or =C22:0) accumulate in X
      linked adrenoleukodystrophy (X-ALD, OMIM 300100), a severe hereditary
      neurodegenerative disease, due to peroxisomal impairment. Previous studies
      analysed the development of X-ALD in humans and gene knockout animal models.
      However, the toxic effect of VLCFA leading to severe symptoms with progressive
      and multifocal demyelination, adrenal insufficiency and inflammation still
      remains unclear. To understand the toxic effects of VLCFA in the brain, here we
      exposed neural cells to VLCFA and analysed the cellular consequences. We found
      that oligodendrocytes and astrocytes challenged with docosanoic- (C22:0),
      tetracosanoic- (C24:0) and hexacosanoic acids (C24:0) die within 24 h. VLCFA
      induced depolarization of mitochondria in situ and increased intracellular Ca2+
      level in all three brain cell types provides indications about the mechanism of
      toxicity of VLCFA. Interestingly, VLCFAs affect to the largest degree the myelin
      producing oligodendrocytes. In isolated mitochondria, VLCFAs exert a detrimental
      effect by affecting the inner mitochondrial membrane and promoting the
      permeability transition. In conclusion, we suggest that there is a potent toxic
      activity of VLCFA due to dramatic cell physiological effects with mitochondrial
      dysfunction and Ca2+ deregulation. This provides the first evidence for
      mitochondrial-based cell death mechanisms in neurodegenerative disease with
      peroxisomal defects and subsequent VLCFA accumulation.

PMID- 18344356
TI  - Non-surgical management of uterine fibroids.
AB  - BACKGROUND: Efforts to develop alternatives to surgery for management of
      symptomatic uterine fibroids have provided new techniques and new medications.
      This review summarizes the existing literature on uterine artery embolization
      (UAE) and investigational studies on four newer approaches. METHODS: PubMed,
      Cochrane and Embase were searched up to December 2007. Studies reporting side
      effects and complications and presenting numerical data on at least one outcome
      measure were included. RESULTS: Case studies report 50-60% reduction in fibroid
      size and 85-95% relief of symptoms following UAE. The largest of these studies
      reported an in-hospital complication rate of 2.7% (90 of 3041 patients) and a
      post-discharge complication rate of 26% (710 of 2729 patients). Eight studies
      compared UAE with conventional surgery. Best evidence suggested that UAE offered
      shorter hospital stays (1-2 days UAE versus 5-5.8 days surgery, 3 randomized
      controlled trials (RCTs)) and recovery times (9.5-28 days UAE versus 36.2-63 days
      surgery, 3 RCTs) and similar major complication rates (2-15% UAE versus 2.7-20%
      surgery, 3 RCTs). Four studies analysing cost-effectiveness found UAE more cost
      effective than surgery. There is insufficient evidence regarding fertility and
      pregnancy outcome after UAE. Five feasibility studies after transvaginal
      temporary uterine artery occlusion in 75 women showed a 40-50% reduction in
      fibroid volume and two early studies using magnetic resonance guided-focused
      ultrasound showed symptom relief at 6 months in 71% of 109 women. Two small RCTs
      assessing mifepristone and asoprisnil showed promising results. CONCLUSIONS: Good
      quality evidence supports the safety and effectiveness of UAE for women with
      symptomatic fibroids. The current available data are insufficient to routinely
      offer UAE to women who wish to preserve or enhance their fertility. Newer
      treatments are still investigational.

PMID- 18344357
TI  - Ultrastructural characterization of the prokaryotic symbiosis in
      "Chlorochromatium aggregatum".
AB  - The phototrophic consortium "Chlorochromatium aggregatum" currently represents
      the most highly developed interspecific association of bacteria and consists of
      green sulfur bacteria, so-called epibionts, surrounding a central, motile,
      chemotrophic bacterium. In order to identify subcellular structures
      characteristic of this symbiosis, consortia were studied by a combination of high
      resolution analytical scanning electron microscopy, transmission electron
      microscopy, and three-dimensional reconstruction and image analyses. Epibionts
      are interconnected and to a lesser extent are also connected with the central
      bacterium, by electron-dense, hair-like filaments. In addition, numerous
      periplasmic tubules extend from the outer membrane of the central bacterium and
      are in direct contact with the outer membrane of the epibionts. In each epibiont
      cell, the attachment site to the central bacterium is characterized by the
      absence of chlorosomes and an additional 17-nm-thick layer (epibiont contact
      layer [ECL]) attached to the inner side of the cytoplasmic membrane. The ECL is
      only occasionally observed in pure cultures of the epibiont, where it occurs in
      about 10 to 20% of the free-living cells. A striking feature of the central
      bacterium is the presence of one or two hexagonally packed flat crystals (central
      bacterium crystal [CBC]) per cell. The CBC reaches 1 microm in length, is 35 nm
      thick, and consists of bilayers of subunits with a spacing of 9 nm. A detailed
      model for consortia is presented, summarizing our conclusions regarding (i)
      cohesion of the cells, (ii) common periplasmic space between the central
      bacterium and the epibiont, (iii) ECL as a symbiosis-specific structure, and (iv)
      formation of the interior paracrystalline structures, central bacterium membrane
      layer, and CBC.

PMID- 18344358
TI  - Stabilization of pSW100 from Pantoea stewartii by the F conjugation system.
AB  - Plasmid pSW100 is 1 of the 13 plasmids from Pantoea stewartii subsp. stewartii
      SW2 which has a replicon that resembles that of ColE1. This work uses a pSW100
      derivative, pSW140K, to study how the pSW100 replicon is stably maintained in its
      hosts. Our results indicate that although pSW140K is stable in Escherichia coli
      HB101, the plasmid is rapidly lost in another E. coli strain, DH5alpha,
      indicating that the genetic background of an E. coli strain affects the stability
      of pSW140K. Mutagenesis of E. coli HB101 with EZ::TN <DHFR-1> revealed that
      mutations in traC, traF, traG, traN, and traV, which encode the components of the
      sex pilus assembly, reduce plasmid stability. Furthermore, this work identified
      that a 38-bp region located immediately upstream of the RNAII promoter is
      critical to the maintenance of plasmid stability in E. coli HB101. TraC binds to
      the region, and in addition, deleting the region destabilizes the plasmid.
      Furthermore, inserting this 38-bp fragment into a plasmid that contains the
      minimal replicon from pSW200 stabilizes the plasmid in E. coli HB101.
      Fluorescence in situ hybridization and immunofluorescence staining also revealed
      that derivatives of pSW100, pSW128A, and TraC are colocalized in cells,
      suggesting that pSW100 may use the sex pilus assembly as a partition apparatus to
      ensure the even distribution of the plasmid during cell division, which may thus
      maintain the plasmid's stability.

PMID- 18344359
TI  - Opine-based Agrobacterium competitiveness: dual expression control of the
      agrocinopine catabolism (acc) operon by agrocinopines and phosphate levels.
AB  - Agrobacterium tumefaciens strain C58 can transform plant cells to produce and
      secrete the sugar-phosphate conjugate opines agrocinopines A and B. The bacterium
      then moves in response to the opines and utilizes them as exclusive sources of
      carbon, energy, and phosphate via the functions encoded by the acc operon. These
      privileged opine-involved activities contribute to the formation of agrobacterial
      niches in the environment. We found that the expression of the acc operon is
      induced by agrocinopines and also by limitation of phosphate. The main promoter
      is present in front of the first gene, accR, which codes for a repressor. This
      operon structure enables efficient repression when opine levels are low. The
      promoter contains two putative operators, one overlapping the -10 sequence and
      the other in the further upstream from it; two partly overlapped putative pho
      boxes between the two operators; and two consecutive transcription start sites.
      DNA fragments containing either of the operators bound purified repressor AccR in
      the absence of agrocinopines but not in the presence of the opines, demonstrating
      the on-off switch of the promoter. Induction of the acc operon can occur under
      low-phosphate conditions in the absence of agrocinopines and further increases
      when the opines also are present. Such opine-phosphate dual regulatory system of
      the operon may ensure maximum utilization of agrocinopines when available and
      thereby increase the chances of agrobacterial survival in the highly competitive
      environment with limited general food sources.

PMID- 18344360
TI  - The virulence regulator Sae of Staphylococcus aureus: promoter activities and
      response to phagocytosis-related signals.
AB  - The two-component system SaeRS of Staphylococcus aureus is closely involved in
      the regulation of major virulence factors. However, little is known about the
      signals leading to saeRS activation. A total of four overlapping transcripts (T1
      to T4) from three different transcription starting points are expressed in the
      sae operon. We used a beta-galactosidase reporter assay to characterize the
      putative promoter regions within the saeRS upstream region. The main transcript
      T2 is probably generated by endoribonucleolytic processing of the T1 transcript.
      Only two distinct promoter elements (P1 and P3) could be detected within the
      saeRS upstream region. The P3 promoter, upstream of saeRS, generates the T3
      transcript, includes a cis-acting enhancer element and is repressed by saeRS. The
      most distal P1 promoter is strongly autoregulated, activated by agr, and
      repressed by sigma factor B. In strain Newman a mutation within the histidine
      kinase SaeS leads to a constitutively activated sae system. Evaluation of
      different external signals revealed that the P1 promoter in strain ISP479R and
      strain UAMS-1 is inhibited by low pH and high NaCl concentrations but activated
      by hydrogen peroxide. The most prominent induction of P1 was observed at
      subinhibitory concentrations of alpha-defensins in various S. aureus strains,
      with the exception of strain ISP479R and strain COL. P1 was not activated by the
      antimicrobial peptides LL37 and daptomycin. In summary, the results indicate that
      the sensor molecule SaeS is activated by alteration within the membrane allowing
      the pathogen to react to phagocytosis related effector molecules.

PMID- 18344361
TI  - Mutations in pimE restore lipoarabinomannan synthesis and growth in a
      Mycobacterium smegmatis lpqW mutant.
AB  - Lipoarabinomannans (LAMs) and phosphatidylinositol mannosides (PIMs) are abundant
      glycolipids in the cell walls of all corynebacteria and mycobacteria, including
      the devastating human pathogen Mycobacterium tuberculosis. We have recently shown
      that M. smegmatis mutants of the lipoprotein-encoding lpqW gene have a profound
      defect in LAM biosynthesis. When these mutants are cultured in complex medium,
      spontaneous bypass mutants consistently evolve in which LAM biosynthesis is
      restored at the expense of polar PIM synthesis. Here we show that restoration of
      LAM biosynthesis in the lpqW mutant results from secondary mutations in the pimE
      gene. PimE is a mannosyltransferase involved in converting AcPIM4, a proposed
      branch point intermediate in the PIM and LAM biosynthetic pathways, to more polar
      PIMs. Mutations in pimE arose due to insertion of the mobile genetic element
      ISMsm1 and independent point mutations that were clustered in predicted
      extracytoplasmic loops of this polytopic membrane protein. Our findings provide
      the first strong evidence that LpqW is required to channel intermediates such as
      AcPIM4 into LAM synthesis and that loss of PimE function results in the
      accumulation of AcPIM4, bypassing the need for LpqW. These data highlight new
      mechanisms regulating the biosynthetic pathways of these essential cell wall
      components.

PMID- 18344362
TI  - Fine-tuning of galactoglucan biosynthesis in Sinorhizobium meliloti by
      differential WggR (ExpG)-, PhoB-, and MucR-dependent regulation of two promoters.
AB  - Depending on the phosphate concentration encountered in the environment
      Sinorhizobium meliloti 2011 synthesizes two different exopolysaccharides (EPS).
      Galactoglucan (EPS II) is produced under phosphate starvation but also in the
      presence of extra copies of the transcriptional regulator WggR (ExpG) or as a
      consequence of a mutation in mucR. The galactoglucan biosynthesis gene cluster
      contains the operons wga (expA), wge (expE), wgd (expD), and wggR (expG). Two
      promoters, differentially controlled by WggR, PhoB, and MucR, were identified
      upstream of each of these operons. The proximal promoters of the wga, wge, and
      wgd transcription units were constitutively active when separated from the
      upstream regulatory sequences. Promoter activity studies and the positions of
      predicted PhoB and WggR binding sites suggested that the proximal promoters are
      cooperatively induced by PhoB and WggR. MucR was shown to strongly inhibit the
      distal promoters and bound to the DNA in the vicinity of the distal transcription
      start sites. An additional inhibitory effect on the distal promoter of the
      structural galactoglucan biosynthesis genes was identified as a new feature of
      WggR in a mucR mutant. A regulatory model of the fine-tuning of galactoglucan
      production is proposed.

PMID- 18344363
TI  - Cold shock exoribonuclease R (VacB) is involved in Aeromonas hydrophila
      pathogenesis.
AB  - In this study, we cloned and sequenced a virulence-associated gene (vacB) from a
      clinical isolate SSU of Aeromonas hydrophila. We identified this gene based on
      our recently annotated genome sequence of the environmental isolate ATCC 7966(T)
      of A. hydrophila and the vacB gene of Shigella flexneri. The A. hydrophila VacB
      protein contained 798 amino acid residues, had a molecular mass of 90.5 kDa, and
      exhibited an exoribonuclease (RNase R) activity. The RNase R of A. hydrophila was
      a cold-shock protein and was required for bacterial growth at low temperature.
      The vacB isogenic mutant, which we developed by homologous recombination using
      marker exchange mutagenesis, was unable to grow at 4 degrees C. In contrast, the
      wild-type (WT) A. hydrophila exhibited significant growth at this low
      temperature. Importantly, the vacB mutant was not defective in growth at 37
      degrees C. The vacB mutant also exhibited reduced motility, and these growth and
      motility phenotype defects were restored after complementation of the vacB
      mutant. The A. hydrophila RNase R-lacking strain was found to be less virulent in
      a mouse lethality model (70% survival) when given by the intraperitoneal route at
      as two 50% lethal doses (LD(50)). On the other hand, the WT and complemented
      strains of A. hydrophila caused 80 to 90% of the mice to succumb to infection at
      the same LD(50) dose. Overall, this is the first report demonstrating the role of
      RNase R in modulating the expression of A. hydrophila virulence.

PMID- 18344364
TI  - The GTPase CpgA is implicated in the deposition of the peptidoglycan sacculus in
      Bacillus subtilis.
AB  - Depletion of the Bacillus subtilis GTPase CpgA produces abnormal cell shapes,
      nonuniform deposition of cell wall, and five- to sixfold accumulation of
      peptidoglycan precursors. Nevertheless, the inherent structure of the cell wall
      appeared mostly unchanged. The results are consistent with CpgA being involved in
      coordinating normal peptidoglycan deposition.

PMID- 18344365
TI  - Concerted action of lactate oxidase and pyruvate oxidase in aerobic growth of
      Streptococcus pneumoniae: role of lactate as an energy source.
AB  - Streptococcus pneumoniae was shown to possess lactate oxidase in addition to well
      documented pyruvate oxidase. The activities of both H(2)O(2)-forming oxidases in
      wild-type cultures were detectable even in the early exponential phase of growth
      and attained the highest levels in the early stationary phase. For each of these
      oxidases, a defective mutant was constructed and compared to the parent regarding
      the dynamics of pyruvate and lactate in aerobic cultures. The results obtained
      indicated that the energy-yielding metabolism in the wild type could be best
      described by the following scheme. (i) As long as glucose is available,
      approximately one-fourth of the pyruvate formed is converted to acetate by the
      sequential action of pyruvate oxidase and acetate kinase with acquisition of
      additional ATP; (ii) the rest of the pyruvate is reduced by lactate dehydrogenase
      to form lactate, with partial achievement of redox balance; (iii) the lactate is
      oxidized by lactate oxidase back to pyruvate, which is converted to acetate as
      described above; and (iv) the sequential reactions mentioned above continue to
      occur as long as lactate is present. As predicted by this model, exogenously
      added lactate was shown to increase the final growth yield in the presence of
      both oxidases.

PMID- 18344366
TI  - Catalytic mechanism of cyclic di-GMP-specific phosphodiesterase: a study of the
      EAL domain-containing RocR from Pseudomonas aeruginosa.
AB  - EAL domain proteins are the major phosphodiesterases for maintaining the cellular
      concentration of second-messenger cyclic di-GMP in bacteria. Given the pivotal
      roles of EAL domains in the regulation of many bacterial behaviors, the
      elucidation of their catalytic and regulatory mechanisms would contribute to the
      effort of deciphering the cyclic di-GMP signaling network. Here, we present data
      to show that RocR, an EAL domain protein that regulates the expression of
      virulence genes and biofilm formation in Pseudomonas aeruginosa PAO-1, catalyzes
      the hydrolysis of cyclic di-GMP by using a general base-catalyzed mechanism with
      the assistance of Mg(2+) ion. In addition to the five essential residues involved
      in Mg(2+) binding, we propose that the essential residue E(352) functions as a
      general base catalyst assisting the deprotonation of Mg(2+)-coordinated water to
      generate the nucleophilic hydroxide ion. The mutation of other conserved residues
      caused various degree of changes in the k(cat) or K(m), leading us to propose
      their roles in residue positioning and substrate binding. With functions assigned
      to the conserved groups in the active site, we discuss the molecular basis for
      the lack of activity of some characterized EAL domain proteins and the
      possibility of predicting the phosphodiesterase activities for the vast number of
      EAL domains in bacterial genomes in light of the catalytic mechanism.

PMID- 18344367
TI  - Evidence that AphB, essential for the virulence of Vibrio vulnificus, is a global
      regulator.
AB  - The Vibrio vulnificus aphB mutant was significantly less virulent than the wild
      type and was impaired in motility and adherence to host cells. Microarray
      analysis revealed that AphB of V. vulnificus (AphB(Vv)) influences the expression
      of over 10% of the V. vulnificus genome. The combined results indicated that
      AphB(Vv) is a global regulator contributing to the pathogenesis of V. vulnificus.

PMID- 18344368
TI  - Regulation of the Bacillus subtilis yciC gene and insights into the DNA-binding
      specificity of the zinc-sensing metalloregulator Zur.
AB  - The Bacillus subtilis Zur protein regulates zinc homeostasis by repressing at
      least 10 genes in response to zinc sufficiency. One of these genes, yciC, encodes
      an abundant protein postulated to function as a metallochaperone. Here, we used a
      genetic approach to identify the cis-acting elements and trans-acting factors
      contributing to the tight repression of yciC. Initial studies led to the
      identification of only trans-acting mutations, and, when the selection was
      repeated using a transposon library, all recovered mutants contained
      insertionally inactivated zur. Using a zur merodiploid strain, we obtained two
      cis-acting mutations that contained large deletions in the yciC regulatory
      region. We demonstrate that the yciC regulatory region contains two functional
      Zur boxes: a primary site (C2) overlapping a sigma(A) promoter approximately 200
      bp upstream of yciC and a second site near the translational start point (C1).
      Zur binds to both of these sites to mediate strong, zinc-dependent repression of
      yciC. Deletion studies indicate that either Zur box is sufficient for repression,
      although repression by Zur bound to C2 is more efficient. Binding studies
      demonstrate that both sites bind Zur with high affinity. Sequence alignment of
      these and previously described Zur boxes suggest that Zur recognizes a more
      extended operator than other Fur family members. We used synthetic
      oligonucleotides to identify bases critical for DNA binding by Zur. Unlike Fur
      and PerR, which bind efficiently to sequences containing a core 7-1-7 repeat
      element, Zur requires a 9-1-9 inverted repeat for high-affinity binding.

PMID- 18344370
TI  - Latent variable modelling.

PMID- 18344369
TI  - Proteins found in a CikA interaction assay link the circadian clock, metabolism,
      and cell division in Synechococcus elongatus.
AB  - Diverse organisms time their cellular activities to occur at distinct phases of
      Earth's solar day, not through the direct regulation of these processes by light
      and darkness but rather through the use of an internal biological (circadian)
      clock that is synchronized with the external cycle. Input pathways serve as
      mechanisms to transduce external cues to a circadian oscillator to maintain
      synchrony between this internal oscillation and the environment. The circadian
      input pathway in the cyanobacterium Synechococcus elongatus PCC 7942 requires the
      kinase CikA. A cikA null mutant exhibits a short circadian period, the inability
      to reset its clock in response to pulses of darkness, and a defect in cell
      division. Although CikA is copurified with the Kai proteins that constitute the
      circadian central oscillator, no direct interaction between CikA and either KaiA,
      KaiB, or KaiC has been demonstrated. Here, we identify four proteins that may
      help connect CikA with the oscillator. Phenotypic analyses of null and
      overexpression alleles demonstrate that these proteins are involved in at least
      one of the functions--circadian period regulation, phase resetting, and cell
      division--attributed to CikA. Predictions based on sequence similarity suggest
      that these proteins function through protein phosphorylation, iron-sulfur cluster
      biosynthesis, and redox regulation. Collectively, these results suggest a model
      for circadian input that incorporates proteins that link the circadian clock,
      metabolism, and cell division.

PMID- 18344371
TI  - A direct test of the hypothesis that increased microtubule network density
      contributes to contractile dysfunction of the hypertrophied heart.
AB  - Contractile dysfunction in pressure overload-hypertrophied myocardium has been
      attributed in part to the increased density of a stabilized cardiocyte
      microtubule network. The present study, the first to employ wild-type and mutant
      tubulin transgenes in a living animal, directly addresses this microtubule
      hypothesis by defining the contractile mechanics of the normal and hypertrophied
      left ventricle (LV) and its constituent cardiocytes from transgenic mice having
      cardiac-restricted replacement of native beta(4)-tubulin with beta(1)-tubulin
      mutants that had been selected for their effects on microtubule stability and
      thus microtubule network density. In each case, the replacement of cardiac
      beta(4)-tubulin with mutant hemagglutinin-tagged beta(1)-tubulin was well
      tolerated in vivo. When LVs in intact mice and cardiocytes from these same LVs
      were examined in terms of contractile mechanics, baseline function was reduced in
      mice with genetically hyperstabilized microtubules, and hypertrophy-related
      contractile dysfunction was exacerbated. However, in mice with genetically
      hypostabilized cardiac microtubules, hypertrophy-related contractile dysfunction
      was ameliorated. Thus, in direct support of the microtubule hypothesis, we show
      here that cardiocyte microtubule network density, as an isolated variable, is
      inversely related to contractile function in vivo and in vitro, and microtubule
      instability rescues most of the contractile dysfunction seen in pressure overload
      hypertrophied myocardium.

PMID- 18344372
TI  - Transcription repression and blocks in cell cycle progression in hypoplastic left
      heart syndrome.
AB  - Hypoplastic left heart syndrome (HLHS) is characterized by abnormally developed
      atrial septum and a severe underdevelopment of the left side of the heart.
      Despite significant advances in its surgical management, little is known about
      the molecular abnormalities in this syndrome. To gain molecular insights into
      HLHS, expression profiling by gene-chip microarray (Affymetrix U133 2.0) and by
      real-time RT-PCR was performed in the atrial septum of patients diagnosed with
      HLHS and compared with age-matched non-HLHS patients. Hierarchical clustering of
      all expressed genes with a P < 0.01 of all tissue samples showed two main
      clusters, one of HLHS and the other of non-HLHS, suggesting different expression
      patterns by the two groups. Net affix followed by real-time RT-PCR analysis
      identified the differentially expressed genes to be those involved in chromatin
      remodeling, cell cycle regulation, and transcriptional regulation. These included
      remodeling factors, histone deactylase 2 and SET and MYND domain containing 1;
      transcription factors, FoxP1, and components of the calcineurin-nuclear factor of
      activated T cells signaling pathway; and cell cycle regulators, cyclin-dependent
      kinase (CDK)-4, phosphatase and tensin homolog, and p18. Since these factors play
      essential roles in heart growth and development, the abnormal expression pattern
      suggests that these molecules may contribute to the pathogenesis of HLHS.

PMID- 18344373
TI  - Differential arterial blood flow response of splanchnic and renal organs during
      low-intensity cycling exercise in women.
AB  - To investigate the regional hemodynamic responses of abdominal arteries at the
      onset of exercise and to focus on their transient responses, eight female
      subjects (21-30 yr) performed ergometer cycling exercise at 40 W for 4 min in a
      semi-supine position. Mean blood velocities (MBVs) in the right renal (RA),
      superior mesenteric (SMA), and splenic (SA) arteries were measured by pulsed echo
      Doppler ultrasonography, with beat-by-beat measurements of heart rate (HR) and
      mean arterial pressure (MAP). The vascular resistance index (RI) of each artery
      was calculated from MBV/MAP. MAP (76 +/- 9 to 83 +/- 8 mmHg at 4 min) and HR (60
      +/- 7 to 101 +/- 9 beats/min at 4 min) increased during exercise (P < 0.05). The
      MBV of RA and SA rapidly decreased after the onset of exercise (30 s; -19 +/- 5%
      and -19 +/- 12%, respectively), reaching -27 +/- 7% and -27 +/- 15% at the end of
      exercise (P < 0.05). RI did not change during the initial 30 s of exercise,
      reflecting a reduction in MAP, and increased toward the end of the exercise (+55
      +/- 21% and +59 +/- 39%, respectively). In contrast, both the MBV and RI in the
      SMA remained constant throughout the exercise. The results indicate that, whereas
      the responses of renal and splenic vessels changed similarly throughout the
      protocol, the vascular response of SMA that mainly supplies blood to the
      intestinal tract was unchanged during exercise. We, therefore, conclude that low
      intensity cycling exercise resulted in differential blood flow responses in
      arteries supplying the abdominal organs.

PMID- 18344374
TI  - Posttranslational modification of voltage-dependent potassium channel Kv1.5: COOH
      terminal palmitoylation modulates its biological properties.
AB  - The physiological function of ion channels is affected by protein-protein and
      protein-membrane interactions that modulate their activity and/or localization.
      Palmitoylation modulates protein function by facilitating targeted membrane
      association, interaction with other proteins, and determining subcellular
      localization. In this study, we demonstrate that the voltage-dependent potassium
      (Kv) channel Kv1.5 is palmitoylated and that the mutation of COOH-terminal
      cysteines is sufficient to abolish the palmitoylation of the Kv1.5 polypeptide in
      Chinese hamster ovary (CHO) cells. The labeling represented the thioester linkage
      of the labeled palmitic acid to cysteine rather than amide and oxygen ester
      linkages as judged by the release of the palmitic acid upon the treatment of the
      gel with hydroxylamine at a neutral pH. Site-directed mutagenesis and
      radiolabeling studies revealed that C593 was the sole site of palmitoylation. The
      elucidation of the biological function of palmitoylation revealed that the
      expression of the FLAG-Kv1.5 palmitoylation-deficient mutant (FL-Kv1.5(Palm-)) in
      stable CHO cells increased membrane expression as determined by the biotinylation
      of surface proteins and quantitative immunofluorescence analyses of these cells,
      in turn enhancing the outward potassium current. This enhanced surface expression
      and the currents were consequential to the slower rate of internalization,
      causing an increased localization of FL-Kv1.5(Palm-) in the plasma membrane
      compared with the wild-type FL-Kv1.5 channels. We conclude that the Kv1.5 channel
      is palmitoylated and that its palmitoylation modulates its biological functions
      and, therefore, might provide a physiological link between the metabolic state
      and the expression of Kv1.5 on the plasma membrane.

PMID- 18344375
TI  - Angiopoietin-1 inhibits intrinsic apoptotic signaling and vascular
      hyperpermeability following hemorrhagic shock.
AB  - Studies from our laboratory demonstrated the involvement of intrinsic apoptotic
      signaling in hyperpermeability following hemorrhagic shock (HS). Angiopoietin 1
      (Ang-1), a potent inhibitor of hyperpermeability, was recently shown to inhibit
      apoptosis. The purpose of our study was to determine the effectiveness of Ang-1
      in attenuating HS-induced hyperpermeability and its relationship to apoptotic
      signaling. HS was induced in rats by withdrawing blood to reduce the mean
      arterial pressure to 40 mmHg for 1 h, followed by reperfusion. Mesenteric
      postcapillary venules were examined for changes in hyperpermeability by
      intravital microscopy. Mitochondrial release of second mitochondrial derived
      activator of caspases (smac) and cytochrome c were determined by Western blot and
      ELISA, respectively. Caspase-3 activity was determined by fluorometric assay.
      Parallel studies were performed in rat lung microvascular endothelial cell
      (RLMEC) monolayers, utilizing HS serum and the proapoptotic Bcl-2 homologous
      antagonist/killer [BAK (BH3)] peptide as inducers of hyperpermeability. In rats,
      Ang-1 (200 ng/ml) attenuated HS-induced hyperpermeability versus the HS group (P
      < 0.05). Ang-1 prevented HS-induced collapse of mitochondrial transmembrane
      potential (DeltaPsi(m)), smac and cytochrome c release, and caspase-3 activity (P
      < 0.05). In RLMEC monolayers, HS serum and BAK (BH3) peptide both induced
      hyperpermeability that was inhibited by Ang-1 (P < 0.05). Ang-1 attenuated HS and
      BAK (BH3) peptide-induced collapse of DeltaPsi(m), smac release, cytochrome c
      release, activation of caspase-3, and vascular hyperpermeability. In vivo, BAK
      (BH3) induced vascular hyperpermeability that was attenuated by Ang-1 (P < 0.05).
      These findings suggest that Ang-1's role in maintaining microvascular endothelial
      barrier integrity involves the intrinsic apoptotic signaling cascade.

PMID- 18344377
TI  - Why can't I make neurological diagnoses anymore?

PMID- 18344376
TI  - Estrogen, nitric oxide, and hypertension differentially modulate agonist-induced
      contractile responses in female transgenic (mRen2)27 hypertensive rats.
AB  - Clinical trials revealed that estrogen may result in cardiovascular risk in
      patients with coronary heart disease, despite earlier studies demonstrating that
      estrogen provided cardiovascular protection. It is possible that the preexisting
      condition of hypertension and the ability of estrogen to activate the renin
      angiotensin system could confound its beneficial effects. Our hypothesis is that
      the attenuation of estrogen to agonist-induced vasoconstrictor responses through
      the activation of nitric oxide (NO) synthase (NOS) is impaired by hypertension.
      We investigated the effects of 17beta-estradiol (E(2)) replacement in
      normotensive Sprague-Dawley (SD) and (mRen2)27 hypertensive transgenic (TG) rats
      on contractile responses to three vasoconstrictors, angiotensin II (ANG II),
      serotonin (5-HT), and phenylephrine (PE), and on the modulatory role of vascular
      NO to these responses. The aorta was isolated from ovariectomized SD and TG rats
      treated chronically with 5 mg E(2) or placebo (P). The isometric tension of the
      aortic rings was measured in organ chambers, and endothelial NOS (eNOS) in the
      rat aorta was detected using Western blot analysis. E(2) treatment increased eNOS
      expression in the SD and TG aorta and reduced ANG II- and 5-HT- but not PE
      induced contractions in SD and TG rats. The inhibition of NOS with N(omega)-nitro
      L-arginine methyl ester enhanced ANG II-, 5-HT-, and PE-induced contractions in P
      treated and ANG II and PE responses in E(2)-treated SD and TG rats. Only the
      responses to 5-HT were augmented in hypertensive rats. In conclusion, this study
      shows that the preexisting condition of hypertension augmented the vascular
      responsiveness of 5-HT, whereas the attenuation of estrogen by ANG II and 5-HT
      vascular responses was not impaired by hypertension. The adrenergic agonist was
      unresponsive to estrogen treatment. The contribution of NO as a factor
      contributing to the relative refractoriness of the vascular responses is
      dependent on the nature of the vasoconstrictor and/or the presence of estrogen.

PMID- 18344378
TI  - Neurological complications of coeliac disease: what is the evidence?
AB  - Coeliac disease is a chronic immune-mediated disorder that primarily affects the
      gastrointestinal tract. There is an inflammatory response in the intestine to the
      ingestion of gluten which improves with a gluten-free diet. Many patients,
      especially adults, may be asymptomatic or have only extraintestinal symptoms at
      onset without any of the classical coeliac symptoms. In the last two decades
      there have been increasing numbers of reports describing neurological
      complications of coeliac disease, especially ataxia, peripheral neuropathy and
      epilepsy. This literature has become quite controversial, with disputes over the
      definition of coeliac disease and gluten sensitivity, whether neurological
      complications are caused by coeliac disease or are epiphenomena, and whether the
      proposed complications respond to a gluten-free diet. This review uses an
      evidence-based approach to critically assess this literature and provides
      guidelines for the evaluation and management of these patients.

PMID- 18344379
TI  - Myelopathy but normal MRI: where next?
AB  - For most patients presenting with a spinal cord syndrome MR scanning has become
      the key investigation in establishing the diagnosis. However, myelopathy with
      normal spinal imaging remains a common clinical conundrum. In this review we
      discuss the diagnoses to consider for the neurologist presented with a patient
      with "MR normal myelopathy". We will illustrate this scenario with a series of
      short cases and consider the further investigation of "MRI normal" myelopathy.

PMID- 18344380
TI  - When the patient fails to respond to treatment: TIAs that go on, and on.
AB  - Most transient ischaemic attacks (TIAs) stop, with or without treatment, but some
      are followed by stroke within days or longer. But if the TIAs do not stop then
      the diagnosis must be reviewed (are they really TIAs or could they be migraine or
      epilepsy?), and if they are TIAs, what are they caused by (atherothromboembolism,
      embolism from the heart, etc)? With this information, both the medical and any
      surgical treatment can be optimised, even though one must accept that the
      randomised controlled trials mostly have not addressed the particular issue of
      continuing TIAs.

PMID- 18344381
TI  - Fatal subacute necrotising brainstem encephalitis in a young man due to a rare
      parasitic (Balamuthia) infection.
AB  - We describe a case of brainstem inflammation in a young man which at first defied
      diagnosis. However, after his death, and notwithstanding our inability to find a
      cause at autopsy, we did not give up. After sending paraffin blocks to the
      Centers for Disease Control in Atlanta, Georgia, USA, they suggested the
      diagnosis of Balamuthia (amoebic) infection.

PMID- 18344382
TI  - Leber's hereditary optic neuropathy associated with multiple sclerosis: Harding's
      syndrome.
AB  - We describe a 32-year-old woman with sequential, severe, painless visual loss in
      one eye and then the other, and three temporally distinct episodes of
      neurological disturbance suggestive of demyelination in the spinal cord. She was
      positive for the T14484C mutation in the mitochondrial genome, one of three
      common mutations causing Leber's hereditary optic neuropathy. In addition, MRI
      identified areas of demyelination within the periventricular white matter of the
      brain and within the spinal cord. The coexistence of multiple sclerosis and
      Leber's hereditary optic neuropathy (Harding's syndrome) is known to occur more
      often than would be expected by chance; therefore, screening for the Leber's
      mutations in multiple sclerosis patients with severe visual loss should be
      considered because this has important prognostic and genetic implications.

PMID- 18344383
TI  - Atrophy of the superior oblique muscle.

PMID- 18344384
TI  - A cyclist with a focal neurological episode.

PMID- 18344385
TI  - Calgary, Canada.

PMID- 18344386
TI  - Four weeks' corticosteroid inhalation does not augment maximal power output in
      endurance athletes.
AB  - OBJECTIVE: To assess possible ergogenic properties of corticosteroid
      administration. DESIGN: A balanced, double-blind, placebo-controlled design was
      used. PARTICIPANTS: 28 well-trained cyclists and rowers. INTERVENTION: 4 weeks'
      daily inhalation of 800 microg budesonide or placebo. MAIN OUTCOME MEASUREMENTS:
      The subjects performed three incremental cycle ergometer tests until exhaustion,
      before and after 2 and 4 weeks of placebo or budesonide administration, to
      measure maximal power output (W(max)). Once a week they filled in a profile of
      mood state (POMS) questionnaire. RESULTS: There was no significant difference in
      W(max) between the placebo (376 (SD 25) W) and the corticosteroid group (375 (36)
      W) during the preintervention test, and there were no significant changes in
      either group after 2 and 4 weeks of intervention. No effect of the intervention
      on mood state was found. CONCLUSION: 4 weeks of corticosteroid or placebo
      inhalation in healthy, well-trained athletes did not affect maximal power output
      or mood state. Hence no ergogenic properties of 4 weeks' corticosteroid
      administration could be demonstrated, which corroborates previous studies of
      short-term corticosteroid administration.

PMID- 18344387
TI  - Bringing cognitive testing into the real world.

PMID- 18344388
TI  - The apolipoprotein-epsilon4 gene: always harmful?

PMID- 18344389
TI  - Current to the brain improves word-finding difficulties in aphasic patients.

PMID- 18344390
TI  - Neurological picture. Extensive cerebral calcification in a patient with systemic
      lupus erythematosus.

PMID- 18344391
TI  - Creatine treatment in muscle disorders: a meta-analysis of randomised controlled
      trials.

PMID- 18344392
TI  - Parkinson's disease: clinical features and diagnosis.
AB  - OBJECTIVE: Parkinson's disease (PD) is a progressive neurological disorder
      characterised by a large number of motor and non-motor features that can impact
      on function to a variable degree. This review describes the clinical
      characteristics of PD with emphasis on those features that differentiate the
      disease from other parkinsonian disorders. METHODS: A MedLine search was
      performed to identify studies that assess the clinical characteristics of PD.
      Search terms included "Parkinson's disease", "diagnosis" and "signs and
      symptoms". RESULTS: Because there is no definitive test for the diagnosis of PD,
      the disease must be diagnosed based on clinical criteria. Rest tremor,
      bradykinesia, rigidity and loss of postural reflexes are generally considered the
      cardinal signs of PD. The presence and specific presentation of these features
      are used to differentiate PD from related parkinsonian disorders. Other clinical
      features include secondary motor symptoms (eg, hypomimia, dysarthria, dysphagia,
      sialorrhoea, micrographia, shuffling gait, festination, freezing, dystonia,
      glabellar reflexes), non-motor symptoms (eg, autonomic dysfunction,
      cognitive/neurobehavioral abnormalities, sleep disorders and sensory
      abnormalities such as anosmia, paresthesias and pain). Absence of rest tremor,
      early occurrence of gait difficulty, postural instability, dementia,
      hallucinations, and the presence of dysautonomia, ophthalmoparesis, ataxia and
      other atypical features, coupled with poor or no response to levodopa, suggest
      diagnoses other than PD. CONCLUSIONS: A thorough understanding of the broad
      spectrum of clinical manifestations of PD is essential to the proper diagnosis of
      the disease. Genetic mutations or variants, neuroimaging abnormalities and other
      tests are potential biomarkers that may improve diagnosis and allow the
      identification of persons at risk.

PMID- 18344393
TI  - Neurological picture. "Hand knob" infarction.

PMID- 18344394
TI  - Neurological picture. Spontaneous intracranial hypotension, hygromata and
      haematomata.

PMID- 18344395
TI  - A case report on fixation instability in Parkinson's disease with bilateral deep
      brain stimulation implants.
AB  - We report on fixation instabilities in a patient diagnosed with Parkinson's
      disease (PD). This patient underwent deep brain stimulation (DBS) surgery
      bilaterally in the vicinity of the subthalamic nuclei (STN). Examination of the
      eye movements of this patient revealed marked fixation instability compared with
      a healthy age matched control. The eye movements occurring during fixation
      differed from other reports of fixation instabilities in that they interrupted
      fixation for only brief durations. These interruptive saccades (IS) had saccade
      like amplitude velocity relationships. The frequency of these IS was higher in
      the patient with PD than in the healthy age matched control. Furthermore, the
      frequency of the IS in the patient reduced toward control with application of
      bilateral DBS in the vicinity of the STN. From our observations we conclude that
      fixation ability may be altered in PD and improved with DBS.

PMID- 18344396
TI  - A longitudinal study of variations in and predictors of fatigue in multiple
      sclerosis.
AB  - OBJECTIVES: To describe variations in fatigue over the course of 2 years in a
      sample of persons with multiple sclerosis (MS), and to investigate the predictive
      value of the following variables on variations in fatigue: sex, age, sense of
      coherence, living with a partner, living with children, work status,
      immunomodulatory treatment, mood, disease severity, disease course, time since
      diagnosis and time. METHODS: Every 6 months, 219 outpatients at an MS specialist
      clinic were assessed using the Fatigue Severity Scale (FSS). Predictive values
      were explored with Generalised Estimating Equation employing proportional odds
      models; FSS scores were categorised as non-fatigue, borderline fatigue or
      fatigue. RESULTS: FSS scores varied significantly (p = 0.02); 54% changed FSS
      category one or several times, 27% were persistently fatigued and 19%
      persistently non-fatigued. Independent predictors of increased fatigue were
      depressive symptoms, weak/moderate sense of coherence, living with a partner and
      not working. Furthermore, moderate disease severity predicted increase when
      combined with >10 years since diagnosis or a progressive course. Independent
      predictors of decreased fatigue were no depressive symptoms, strong sense of
      coherence, living alone and working. Moreover, mild and severe disease predicted
      a decrease when combined with >10 years since diagnosis, and mild severity
      combined with a progressive course. CONCLUSION: Mood, sense of coherence and
      living with a partner were independent predictors of fatigue in persons with MS.
      In addition to monitoring disease related variables, health related services
      should apply a broad range of approaches and repeatedly assess fatigue in persons
      with MS, to provide preventive care and appropriate interventions.

PMID- 18344397
TI  - Bedside differentiation of vestibular neuritis from central "vestibular
      pseudoneuritis".
AB  - Acute unilateral peripheral and central vestibular lesions can cause similar
      signs and symptoms, but they require different diagnostics and management. We
      therefore correlated clinical signs to differentiate vestibular neuritis (40
      patients) from central "vestibular pseudoneuritis" (43 patients) in the acute
      situation with the final diagnosis assessed by neuroimaging. Skew deviation was
      the only specific but non-sensitive (40%) sign for pseudoneuritis. None of the
      other isolated signs (head thrust test, saccadic pursuit, gaze evoked nystagmus,
      subjective visual vertical) were reliable; however, multivariate logistic
      regression increased their sensitivity and specificity to 92%.

PMID- 18344398
TI  - Asymmetrical late onset motor neuropathy associated with a novel mutation in the
      small heat shock protein HSPB1 (HSP27).
AB  - Distal hereditary motor neuropathy, also known as distal spinal muscular atrophy,
      is characterised by slowly progressive weakness and wasting of the hands and feet
      and has a heterogeneous genetic basis. One form of distal hereditary motor
      neuropathy is associated with mutations in the gene for the small heat shock
      protein HSPB1 (hsp27). Families have been described in which slowly progressive,
      symmetrical, lower limb predominant motor weakness is usually evident by middle
      age. Here we report a novel mutation, G84R, in an elderly patient presenting with
      strikingly asymmetrical weakness. Expression of this and other known mutations in
      cell culture demonstrated enhanced aggregation of mutant HSPB1 protein compared
      with wild-type.

PMID- 18344399
TI  - Interleukin 6 gene polymorphisms are not associated with aneurysmal subarachnoid
      haemorrhage in an Italian population.
AB  - OBJECTIVE: Several lines of evidence indicate a role for inflammatory processes
      in the development of cerebral aneurysms. Recently, polymorphisms in the promoter
      region of the interleukin 6 (IL6) gene were shown to be associated with
      intracranial aneurysmal disease. The purpose of this study was to verify the
      association of two functionally active polymorphisms (-174 G>C and -572 G>C) in
      the promoter region of the IL6 gene with the risk and clinical features of
      aneurysmal subarachnoid haemorrhage (SAH) in an Italian population. METHODS: A
      total of 179 consecutive aneurysmal SAH patients and 156 healthy controls were
      involved in the study. Cases and controls were genotyped for the -174 G<C and the
      -572 G<C biallelic polymorphisms of the IL6 gene. The frequencies of different
      promoter haplotypes were compared between cases and controls. RESULTS: Allelic
      and genotypic frequencies of the examined polymorphism were not significantly
      different between cases and controls. Inferred haplotypes were not significantly
      different in both groups. Finally, the different IL6 genotypes did not seem to
      significantly modify the main clinical features of the disease. CONCLUSIONS: Our
      study did not confirm the association between functionally active polymorphisms
      in the IL6 gene and the risk of aneurysmal SAH in an Italian population.
      Additional studies in different populations are warranted to clarify the role of
      the IL6 gene in the pathogenesis of aneurysmal SAH.

PMID- 18344400
TI  - Kinnier Wilson and Sherrington.

PMID- 18344401
TI  - Bilateral vertebral artery dissection and infratentorial stroke complicated by
      stress-induced cardiomyopathy.

PMID- 18344402
TI  - Bilateral mesial temporal polymicrogyria: a case report.

PMID- 18344403
TI  - Sub-acute demyelinating neuropathy associated with an NK/T cell lymphoma.

PMID- 18344406
TI  - Schizosaccharomyces pombe Hst4 functions in DNA damage response by regulating
      histone H3 K56 acetylation.
AB  - The packaging of eukaryotic DNA into chromatin is likely to be crucial for the
      maintenance of genomic integrity. Histone acetylation and deacetylation, which
      alter chromatin accessibility, have been implicated in DNA damage tolerance. Here
      we show that Schizosaccharomyces pombe Hst4, a homolog of histone deacetylase
      Sir2, participates in S-phase-specific DNA damage tolerance. Hst4 was essential
      for the survival of cells exposed to the genotoxic agent methyl methanesulfonate
      (MMS) as well as for cells lacking components of the DNA damage checkpoint
      pathway. It was required for the deacetylation of histone H3 core domain residue
      lysine 56, since a strain with a point mutation of its catalytic domain was
      unable to deacetylate this residue in vivo. Hst4 regulated the acetylation of H3
      K56 and was itself cell cycle regulated. We also show that MMS treatment resulted
      in increased acetylation of histone H3 lysine 56 in wild-type cells and hst4Delta
      mutants had constitutively elevated levels of histone H3 K56 acetylation.
      Interestingly, the level of expression of Hst4 decreased upon MMS treatment,
      suggesting that the cell regulates access to the site of DNA damage by changing
      the level of this protein. Furthermore, we find that the phenotypes of both K56Q
      and K56R mutants of histone H3 were similar to those of hst4Delta mutants,
      suggesting that proper regulation of histone acetylation is important for DNA
      integrity. We propose that Hst4 is a deacetylase involved in the restoration of
      chromatin structure following the S phase of cell cycle and DNA damage response.

PMID- 18344407
TI  - MADS-box transcription factor mig1 is required for infectious growth in
      Magnaporthe grisea.
AB  - Magnaporthe grisea is a model fungus for studying fungus-plant interactions. Two
      mitogen-activated protein (MAP) kinase genes, PMK1 and MPS1, have been implicated
      in regulating plant infection processes in M. grisea. However, transcription
      factors activated by these MAP kinases are not well studied. In this study we
      functionally characterized the MIG1 gene that encodes a MADS-box transcription
      factor homologous to Saccharomyces cerevisiae Rlm1. In yeast two-hybrid assays,
      MIG1 interacts with MPS1, suggesting that MIG1 may function downstream from the
      MPS1 pathway. The mig1 deletion mutant had a normal growth rate and formed
      melanized appressoria, but it was nonpathogenic and failed to infect rice leaves
      through wounds. Appressoria formed by the mig1 mutant developed penetration pegs
      and primary infectious hyphae, but further differentiation of the secondary
      infectious hyphae inside live plant cells was blocked. However, the mig1 mutant
      formed infectious hypha-like structures in heat-killed plant cells or cellophane
      membranes. In transformants expressing the MIG1-GFP fusion, green fluorescent
      protein (GFP) signals were not detectable in vegetative hyphae and conidiophores.
      Mig1-GFP was localized to nuclei in conidia, appressoria, and infectious hyphae.
      Deletion of the MADS box had no effect on the expression and localization of the
      MIG1-GFP fusion but eliminated its ability to complement the mig1 mutant. These
      results suggest that MIG1 may be required for overcoming plant defense responses
      and the differentiation of secondary infectious hyphae in live plant cells. The
      MADS-box domain is essential for the function of MIG1 but dispensable for its
      nuclear localization, which may be associated with the activation of MIG1 by MPS1
      during conidiation and plant infection.

PMID- 18344408
TI  - Overexpression of squamous cell carcinoma antigen in idiopathic pulmonary
      fibrosis: clinicopathological correlations.
AB  - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder
      with a poor prognosis. Epithelial instability is a crucial step in the
      development and progression of the disease, including neoplastic transformation.
      Few tissue markers for epithelial instability have been reported in IPF. Squamous
      cell carcinoma antigen (SCCA) is a serine protease inhibitor typically expressed
      by dysplastic and neoplastic cells of epithelial origin, more often in squamous
      cell tumours. At present, no information is available on its expression in IPF.
      METHODS: SCCA and transforming growth factor beta (TGFbeta) expression in
      surgical lung biopsies from 22 patients with IPF and 20 control cases was
      examined. An in vitro study using A549 pneumocytes was also conducted to
      investigate the relationship between SCCA and TGFbeta expression. SCCA and
      TGFbeta epithelial expression was evaluated by immunohistochemistry and reverse
      transcription-PCR (RT-PCR). SCCA values were correlated with different
      pathological and clinical parameters. Time course analysis of TGFbeta expression
      in A549 pneumocytes incubated with different SCCA concentrations was assessed by
      real time RT-PCR. RESULTS: SCCA was expressed in many metaplastic alveolar
      epithelial cells in all IPF cases with a mean value of 24.9% while it was seen in
      only two control patients in up to 5% of metaplastic cells. In patients with IPF,
      SCCA correlated positively with extension of fibroblastic foci (r = 0.49, p =
      0.02), expression of TGFbeta (r = 0.78, p<0.0001) and with carbon monoxide
      transfer factor decline after 9 months of follow-up (r = 0.59, p = 0.01). In
      vitro experiments showed that incubation of cultured cells with SCCA induced
      TGFbeta expression, with a peak at 24 h. CONCLUSION: Our findings provide for the
      first time a potential mechanism by which SCCA secreted from metaplastic
      epithelial cells may exert a profibrotic effect in IPF. SCCA could be an
      important biomarker in this incurable disease.

PMID- 18344409
TI  - Alteration of retinal rod outer segment membrane fluidity in a rat model of Smith
      Lemli-Opitz syndrome.
AB  - Smith-Lemli-Opitz syndrome (SLOS) is caused by an inherited defect in the last
      step in cholesterol (Chol) biosynthesis, leading to abnormal accumulation of 7
      dehydrocholesterol and decreased Chol levels. Progressive retinal degeneration
      occurs in an animal model of SLOS, induced by treating rats with AY9944, a
      selective inhibitor of the enzyme affected in SLOS. Here we evaluated alterations
      in the biochemical and physical properties of retinal rod outer segment (ROS)
      membranes in this animal model. At 1 month of AY9944 treatment, there were modest
      alterations in fatty acid composition, but no significant differences in cis
      parinaric acid (cPA) spectroscopic parameters in ROS membranes from treated
      versus control rats. However, at 3 months, ROS docosahexaenoic acid (DHA) content
      was dramatically reduced, and cPA fluorescence anisotropy values were decreased,
      relative to controls. Also, 1,6-diphenyl-1,3,5-hexatriene exhibited decreased
      rotational motion and increased orientational order in ROS membranes from 3 month
      old AY9944-treated rats, relative to controls. No significant changes in
      protein:lipid ratios were observed; however, rhodopsin regenerability was
      compromised by 3 months of treatment. These findings are consistent with reduced
      ROS membrane fluidity in the SLOS rat model, relative to controls, primarily due
      to the dramatic reduction in membrane DHA levels, rather than altered sterol
      composition.

PMID- 18344410
TI  - A novel method for measuring human lipoprotein lipase and hepatic lipase
      activities in postheparin plasma.
AB  - The objective of this study was to establish a new lipoprotein lipase (LPL) and
      hepatic lipase (HL) activity assay method. Seventy normal volunteers were
      recruited. Lipase activities were assayed by measuring the increase in absorbance
      at 546 nm due to the quinoneine dye. Reaction mixture-1 (R-1) contained
      dioleoylglycerol solubilized with lauryldimethylaminobetaine, monoacylglycerol
      specific lipase, glycerolkinase, glycerol-3-phosphate oxidase, peroxidase,
      ascorbic acid oxidase, and apolipoprotein C-II (apoC-II). R-2 contained Tris-HCl
      (pH 8.7) and 4-aminoantipyrine. Automated assay of lipase activities was
      performed with an automatic clinical analyzer. In the assay for HL + LPL
      activity, 160 microl R-1 was incubated at 37 degrees C with 2 microl of sample
      for 5 min, and 80 microl R-2 was added. HL activities were measured under the
      same conditions without apoC-II. HL and LPL activities were also measured by the
      conventional isotope method and for HL mass by ELISA. Lipase activity detected in
      a 1.6 M NaCl-eluted fraction from a heparin-Sepharose column was enhanced by
      adding purified apoC-II in a dose-dependent manner, whereas that eluted by 0.8 M
      NaCl was not. Postheparin plasma-LPL and HL activities measured in the present
      automated method had high correlations with those measured by conventional
      activity and mass methods. This automated assay method for LPL and HL activities
      is simple and reliable and can be applied to an automatic clinical analyzer.

PMID- 18344412
TI  - Alterations to surfactant precede physiological deterioration during high tidal
      volume ventilation.
AB  - Lung injury due to mechanical ventilation is associated with an impairment of
      endogenous surfactant. It is unknown whether this impairment is a consequence of
      or an active contributor to the development and progression of lung injury. To
      investigate this issue, the present study addressed three questions: Do
      alterations to surfactant precede physiological lung dysfunction during
      mechanical ventilation? Which components are responsible for surfactant's
      biophysical dysfunction? Does exogenous surfactant supplementation offer a
      physiological benefit in ventilation-induced lung injury? Adult rats were exposed
      to either a low-stretch [tidal volume (Vt) = 8 ml/kg, positive end-expiratory
      pressure (PEEP) = 5 cmH2O, respiratory rate (RR) = 54-56 breaths/min (bpm),
      fractional inspired oxygen (Fi(O2)) = 1.0] or high-stretch (Vt = 30 ml/kg, PEEP =
      0 cmH2O, RR = 14-16 bpm, Fi(O2) = 1.0) ventilation strategy and monitored for
      either 1 or 2 h. Subsequently, animals were lavaged and the composition and
      function of surfactant was analyzed. Separate groups of animals received
      exogenous surfactant after 1 h of high-stretch ventilation and were monitored for
      an additional 2 h. High stretch induced a significant decrease in blood
      oxygenation after 2 h of ventilation. Alterations in surfactant pool sizes and
      activity were observed at 1 h of high-stretch ventilation and progressed over
      time. The functional impairment of surfactant appeared to be caused by
      alterations to the hydrophobic components of surfactant. Exogenous surfactant
      treatment after a period of high-stretch ventilation mitigated subsequent
      physiological lung dysfunction. Together, these results suggest that alterations
      of surfactant are a consequence of the ventilation strategy that impair the
      biophysical activity of this material and thereby contribute directly to lung
      dysfunction over time.

PMID- 18344413
TI  - Differential effects of intravenous anesthetics on capacitative calcium entry in
      human pulmonary artery smooth muscle cells.
AB  - We assessed the roles of the protein kinase C (PKC) and the tyrosine kinase (TK)
      signaling pathways in regulating capacitative calcium entry (CCE) in human
      pulmonary artery smooth muscle cells (PASMCs) and investigated the effects of
      intravenous anesthetics (midazolam, propofol, thiopental, ketamine, etomidate,
      morphine, and fentanyl) on CCE in human PASMCs. Fura-2-loaded human PASMCs were
      placed in a dish (37 degrees C) on an inverted fluorescence microscope.
      Intracellular Ca2+ concentration ([Ca2+]i) was measured as the 340/380
      fluorescence ratio in individual PASMCs. Thapsigargin, a sarcoplasmic reticulum
      Ca2+-adenosine triphosphatase inhibitor, was used to deplete intracellular Ca2+
      stores after removing extracellular Ca2+. CCE was then activated by restoring
      extracellular Ca2+ (2.2 mM). The effects of PKC activation and inhibition, TK
      inhibition, and the intravenous anesthetics on CCE were assessed. Thapsigargin
      caused a transient increase in [Ca2+]i. Restoring extracellular Ca2+ caused a
      rapid peak increase in [Ca2+]i, followed by a sustained increase in [Ca2+]i;
      i.e., CCE was stimulated in human PASMCs. PKC activation attenuated (P < 0.05),
      whereas PKC inhibition potentiated (P < 0.05), both peak and sustained CCE. TK
      inhibition attenuated (P < 0.05) both peak and sustained CCE. Midazolam,
      propofol, and thiopental each attenuated (P < 0.05) both peak and sustained CCE,
      whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE. Our
      results suggest that CCE in human PASMCs is influenced by both the TK and PKC
      signaling pathways. Midazolam, propofol, and thiopental each attenuated CCE,
      whereas ketamine, etomidate, morphine, and fentanyl had no effect on CCE.

PMID- 18344414
TI  - Apoetm1Unc mice have impaired alveologenesis, low lung function, and rapid loss
      of lung function.
AB  - Diminished lung function, indicated by a low forced expiratory volume in one
      second (FEV1), and short physical stature, predict early mortality from all
      causes, including cardiovascular, among smokers and never smokers. The basis for
      these associations is unclear, and, it is not known if there is a pulmonary
      morphological component to the relationship between low FEV1 and early death in a
      general population. Some apolipoprotein E genotypes also predict atherosclerosis
      and early mortality. These considerations led us to examine the Apoe(tm1Unc)
      (Apoe) mouse, in which the apolipoprotein E gene is deleted, and that develops
      dyslipidemia, atherosclerosis at an early age, and has a shorter life span than
      the founder wild-type (wt) strain. We asked if Apoe mice have a morphological or
      functional pulmonary phenotype. We measured the size, number, and surface area of
      pulmonary gas-exchange units (alveoli) and mechanical properties of the lung.
      Compared with wt mice, Apoe mice had: 1) diminished developmental alveologenesis,
      2) increased airway resistance in early adulthood, 3) high lung volume and high
      dynamic and static compliance in later adulthood, 4) more rapid loss of lung
      recoil with age, and 5) were less long than wt mice. These findings in mice
      indicate the association of a low FEV1 with early death in humans may have
      developmental, and accelerated ageing, related pulmonary components, and that
      dietary, genetic, or dietary and genetic influences, on lipid metabolism may be
      an upstream cause of inflammation and oxidative stress, currently considered to
      be major risk factors for COPD.

PMID- 18344415
TI  - Xanthine oxidoreductase in respiratory and cardiovascular disorders.
AB  - In addition to its critical role in purine metabolism, xanthine oxidoreductase
      (XOR) has been implicated in the development of tissue oxidative damage in a wide
      variety of respiratory and cardiovascular disorders such as acute lung injury,
      ischemia-reperfusion injury, atherosclerosis, heart failure, and arterial
      hypertension. Although much remains to be clarified about the regulation and
      signaling pathways of this enzyme, it is quite evident from abundant
      investigation in animal models and some human trials that XOR inhibition can
      favorably alter critical disease processes and impact outcomes. From promising
      bench-to-bedside data, a better understanding of this enigmatic enzyme is
      emerging. However, the positive findings related to XOR inhibition need to be
      confirmed in large-scale, well-designed clinical trials. This will hopefully
      provide new opportunities for therapeutic intervention. This article reviews the
      available evidence involving XOR in oxidative states with specific emphasis on
      respiratory and cardiovascular diseases.

PMID- 18344416
TI  - Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation
      in response to hyperoxia: ATR-dependent ATM activation.
AB  - Elevated level of oxygen (hyperoxia) is widely used in critical care units and in
      respiratory insufficiencies. In addition, hyperoxia has been implicated in many
      diseases such as bronchopulmonary dysplasia or acute respiratory distress
      syndrome. Although hyperoxia is known to cause DNA base modifications and strand
      breaks, the DNA damage response has not been adequately investigated. We have
      investigated the effect of hyperoxia on DNA damage signaling and show that
      hyperoxia is a unique stress that activates the ataxia telangiectasia mutant
      (ATM)- and Rad3-related protein kinase (ATR)-dependent p53 phosphorylations
      (Ser6, -15, -37, and -392), phosphorylation of histone H2AX (Ser139), and
      phosphorylation of checkpoint kinase 1 (Chk1). In addition, we show that
      phosphorylation of p53 (Ser6) and histone H2AX (Ser139) depend on both ATM and
      ATR. We demonstrate that ATR activation precedes ATM activation in hyperoxia.
      Finally, we show that ATR is required for ATM activation in hyperoxia. Taken
      together, we report that ATR is the major DNA damage signal transducer in
      hyperoxia that activates ATM.

PMID- 18344417
TI  - Characterization of an amino acid permease from the endomycorrhizal fungus Glomus
      mosseae.
AB  - Arbuscular mycorrhizal (AM) fungi are capable of exploiting organic nitrogen
      sources, but the molecular mechanisms that control such an uptake are still
      unknown. Polymerase chain reaction-based approaches, bioinformatic tools, and a
      heterologous expression system have been used to characterize a sequence coding
      for an amino acid permease (GmosAAP1) from the AM fungus Glomus mosseae. The
      GmosAAP1 shows primary and secondary structures that are similar to those of
      other fungal amino acid permeases. Functional complementation and uptake
      experiments in a yeast mutant that was defective in the multiple amino acid
      uptake system demonstrated that GmosAAP1 is able to transport proline through a
      proton-coupled, pH- and energy-dependent process. A competitive test showed that
      GmosAAP1 binds nonpolar and hydrophobic amino acids, thus indicating a relatively
      specific substrate spectrum. GmosAAP1 mRNAs were detected in the extraradical
      fungal structures. Transcript abundance was increased upon exposure to organic
      nitrogen, in particular when supplied at 2 mm concentrations. These findings
      suggest that GmosAAP1 plays a role in the first steps of amino acid acquisition,
      allowing direct amino acid uptake from the soil and extending the molecular tools
      by which AM fungi exploit soil resources.

PMID- 18344418
TI  - Comparison of the dynamics and functional redundancy of the Arabidopsis dynamin
      related isoforms DRP1A and DRP1C during plant development.
AB  - Members of the Arabidopsis (Arabidopsis thaliana) DYNAMIN-RELATED PROTEIN1 (DRP1)
      family are required for cytokinesis and cell expansion. Two isoforms, DRP1A and
      DRP1C, are required for plasma membrane maintenance during stigmatic papillae
      expansion and pollen development, respectively. It is unknown whether the DRP1s
      function interchangeably or if they have distinct roles during cell division and
      expansion. DRP1C was previously shown to form dynamic foci in the cell cortex,
      which colocalize with part of the clathrin endocytic machinery in plants. DRP1A
      localizes to the plasma membrane, but its cortical organization and dynamics have
      not been determined. Using dual color labeling with live cell imaging techniques,
      we showed that DRP1A also forms discreet dynamic foci in the epidermal cell
      cortex. Although the foci overlap with those formed by DRP1C and clathrin light
      chain, there are clear differences in behavior and response to pharmacological
      inhibitors between DRP1A and DRP1C foci. Possible functional or regulatory
      differences between DRP1A and DRP1C were supported by the failure of DRP1C to
      functionally compensate for the absence of DRP1A. Our studies indicated that the
      DRP1 isoforms function or are regulated differently during cell expansion.

PMID- 18344419
TI  - Biosynthesis and accumulation of ergoline alkaloids in a mutualistic association
      between Ipomoea asarifolia (Convolvulaceae) and a clavicipitalean fungus.
AB  - Ergoline alkaloids occur in taxonomically unrelated taxa, such as fungi,
      belonging to the phylum Ascomycetes and higher plants of the family
      Convolvulaceae. The disjointed occurrence can be explained by the observation
      that plant-associated epibiotic clavicipitalean fungi capable of synthesizing
      ergoline alkaloids colonize the adaxial leaf surface of certain Convolvulaceae
      plant species. The fungi are seed transmitted. Their capacity to synthesize
      ergoline alkaloids depends on the presence of an intact differentiated host plant
      (e.g. Ipomoea asarifolia or Turbina corymbosa [Convolvulaceae]). Here, we present
      independent proof that these fungi are equipped with genetic material responsible
      for ergoline alkaloid biosynthesis. The gene (dmaW) for the determinant step in
      ergoline alkaloid biosynthesis was shown to be part of a cluster involved in
      ergoline alkaloid formation. The dmaW gene was overexpressed in Saccharomyces
      cerevisiae, the encoded DmaW protein purified to homogeneity, and characterized.
      Neither the gene nor the biosynthetic capacity, however, was detectable in the
      intact I. asarifolia or the taxonomically related T. corymbosa host plants. Both
      plants, however, contained the ergoline alkaloids almost exclusively, whereas
      alkaloids are not detectable in the associated epibiotic fungi. This indicates
      that a transport system may exist translocating the alkaloids from the epibiotic
      fungus into the plant. The association between the fungus and the plant very
      likely is a symbiotum in which ergoline alkaloids play an essential role.

PMID- 18344420
TI  - Sucrose synthase is associated with the cell wall of tobacco pollen tubes.
AB  - Sucrose synthase (Sus; EC 2.4.1.13) is a key enzyme of sucrose metabolism in
      plant cells, providing carbon for respiration and for the synthesis of cell wall
      polymers and starch. Since Sus is important for plant cell growth, insights into
      its structure, localization, and features are useful for defining the
      relationships between nutrients, growth, and cell morphogenesis. We used the
      pollen tube of tobacco (Nicotiana tabacum) as a cell model to characterize the
      main features of Sus with regard to cell growth and cell wall synthesis. Apart
      from its role during sexual reproduction, the pollen tube is a typical tip
      growing cell, and the proper construction of its cell wall is essential for
      correct shaping and direction of growth. The outer cell wall layer of pollen
      tubes consists of pectins, but the inner layer is composed of cellulose and
      callose; both polymers require metabolic precursors in the form of UDP-glucose,
      which is synthesized by Sus. We identified an 88-kD polypeptide in the soluble,
      plasma membrane and Golgi fraction of pollen tubes. The protein was also found in
      association with the cell wall. After purification, the protein showed an enzyme
      activity similar to that of maize (Zea mays) Sus. Distribution of Sus was
      affected by brefeldin A and depended on the nutrition status of the pollen tube,
      because an absence of metabolic sugars in the growth medium caused Sus to
      distribute differently during tube elongation. Analysis by bidimensional
      electrophoresis indicated that Sus exists as two isoforms, one of which is
      phosphorylated and more abundant in the cytoplasm and cell wall and the other of
      which is not phosphorylated and is specific to the plasma membrane. Results
      indicate that the protein has a role in the construction of the extracellular
      matrix and thus in the morphogenesis of pollen tubes.

PMID- 18344421
TI  - Cell wall modifications in Arabidopsis plants with altered alpha-L
      arabinofuranosidase activity.
AB  - Although cell wall remodeling is an essential feature of plant growth and
      development, the underlying molecular mechanisms are poorly understood. This work
      describes the characterization of Arabidopsis (Arabidopsis thaliana) plants with
      altered expression of ARAF1, a bifunctional alpha-L-arabinofuranosidase/beta-D
      xylosidase (At3g10740) belonging to family 51 glycosyl-hydrolases. ARAF1 was
      localized in several cell types in the vascular system of roots and stems,
      including xylem vessels and parenchyma cells surrounding the vessels, the
      cambium, and the phloem. araf1 T-DNA insertional mutants showed no visible
      phenotype, whereas transgenic plants that overexpressed ARAF1 exhibited a delay
      in inflorescence emergence and altered stem architecture. Although global
      monosaccharide analysis indicated only slight differences in cell wall
      composition in both mutant and overexpressing lines, immunolocalization
      experiments using anti-arabinan (LM6) and anti-xylan (LM10) antibodies indicated
      cell type-specific alterations in cell wall structure. In araf1 mutants, an
      increase in LM6 signal intensity was observed in the phloem, cambium, and xylem
      parenchyma in stems and roots, largely coinciding with ARAF1 expression sites.
      The ectopic overexpression of ARAF1 resulted in an increase in LM10 labeling in
      the secondary walls of interfascicular fibers and xylem vessels. The combined
      ARAF1 gene expression and immunolocalization studies suggest that arabinan
      containing pectins are potential in vivo substrates of ARAF1 in Arabidopsis.

PMID- 18344422
TI  - Protein Z-dependent protease inhibitor deficiency produces a more severe murine
      phenotype than protein Z deficiency.
AB  - Protein Z (PZ) is a plasma vitamin K-dependent protein that functions as a
      cofactor to dramatically enhance the inhibition of coagulation factor Xa by the
      serpin, protein Z-dependent protease inhibitor (ZPI). In vitro, ZPI not only
      inhibits factor Xa in a calcium ion-, phospholipid-, and PZ-dependent fashion,
      but also directly inhibits coagulation factor XIa. In murine gene-deletion
      models, PZ and ZPI deficiency enhances thrombosis following arterial injury and
      increases mortality from pulmonary thromboembolism following collagen/epinephrine
      infusion. On a factor V(Leiden) genetic background, ZPI deficiency produces a
      significantly more severe phenotype than PZ deficiency, implying that factor XIa
      inhibition by ZPI is physiologically relevant. The studies in mice suggest that
      human PZ and ZPI deficiency would be associated with a modest thrombotic risk
      with ZPI deficiency producing a more severe phenotype.

PMID- 18344423
TI  - Basal secretion of von Willebrand factor from human endothelial cells.
AB  - Endothelial cells store the adhesive glycoprotein von Willebrand factor (VWF) in
      Weibel-Palade bodies (WPBs), distinctively shaped regulated secretory organelles
      that undergo exocytosis in response to secretagogue. A significant proportion of
      newly synthesized VWF is also secreted spontaneously from nonstimulated cells,
      through what is thought to be the constitutive secretory pathway. To learn more
      about VWF trafficking, we performed kinetic analyses of the storage and
      nonstimulated secretion of VWF in cultured human endothelial cells. We found that
      most VWF was secreted through a route that was significantly delayed compared
      with constitutive secretion, although this pathway was responsible for secretion
      of a small amount of uncleaved VWF precursor. Disruption of pH-dependent sorting
      processes with ammonium chloride converted the secretion kinetics of mature VWF
      to that of its precursor. Conversely, preventing constitutive secretion of
      nascent protein with brefeldin A had only a modest effect on the spontaneous
      release of VWF, showing that most VWF secreted by nonstimulated cells was not
      constitutive secretion but basal release of a post-Golgi storage organelle,
      presumably the WPB. These data suggest that VWF is sorted to the regulated
      secretory pathway in endothelial cells much more efficiently than previously
      reported.

PMID- 18344424
TI  - Identification of type 1 von Willebrand disease patients with reduced von
      Willebrand factor survival by assay of the VWF propeptide in the European study:
      molecular and clinical markers for the diagnosis and management of type 1 VWD
      (MCMDM-1VWD).
AB  - The decreased survival of von Willebrand factor (VWF) in plasma has been
      implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD)
      patients. We have previously reported that the ratio of plasma levels of VWF and
      its propeptide (VWFpp) can be used to identify patients with reduced VWF
      survival. In this study, we report the assay of VWFpp and VWF:Ag in 19
      individuals recruited from 6 European centers within the MCMDM-1VWD study. Eight
      individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a
      robust desmopressin response and significantly reduced VWF half-life that was
      predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF
      mutations previously associated with reduced VWF survival were identified in each
      of the 7 individuals. Thus, a substantially increased ratio of steady-state
      VWFpp/VWF:Ag predicted a reduced VWF half-life in patients with markedly
      decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found
      in a subpopulation of patients with type 1 VWD. The systematic assay of both
      plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may
      identify patients with a reduced VWF survival phenotype.

PMID- 18344426
TI  - Initial characterization of an 18F-labeled myocardial perfusion tracer.
AB  - PET allows for quantitative, regional myocardial perfusion imaging. The short
      half-lives of the perfusion tracers currently in use limit their clinical
      applicability. Here, the biodistribution and imaging quality of a new 18F-labeled
      myocardial perfusion agent (18F-BMS-747158-02) in an animal model are described.
      METHODS: The biodistribution of 18F-BMS-747158-02 was determined at 10 and 60 min
      after injection. The first-pass extraction fraction of the tracer was measured in
      isolated rat hearts perfused with the Langendorff method. Small-animal PET
      imaging was used to study tracer retention. RESULTS: The biodistribution at 10
      min after injection demonstrated high myocardial uptake (3.1 percentage injected
      dose per gram [%ID/g]) accompanied by little activity in the lungs (0.3 %ID/g)
      and liver (1.0 %ID/g). The tracer showed a high and flow-independent myocardial
      first-pass extraction fraction, averaging 0.94 (SD = 0.04). PET imaging provided
      excellent delineation of myocardial structures. The heart-to-lung activity ratio
      increased from 4.7 to 10.2 between 1 and 15 min after tracer injection (at rest).
      Adenosine infusion (140 microg/kg/min) led to a significant increase in
      myocardial tracer retention (from 1.68 [SD = 0.23]) s(-1) to 3.21 [SD = 0.92] s(
      1); P = 0.03). CONCLUSION: The observation of a high and flow-independent first
      pass extraction fraction promises linearity between tracer uptake and myocardial
      blood flow. Sustained myocardial tracer uptake, combined with high image
      contrast, will allow for imaging protocols with tracer injection at peak exercise
      followed by delayed imaging. Thus, 18F-BMS-747158-02 is a promising new tracer
      for the quantitative imaging of myocardial perfusion and can be distributed to
      imaging laboratories without a cyclotron.

PMID- 18344425
TI  - Wnt3a signaling within bone inhibits multiple myeloma bone disease and tumor
      growth.
AB  - Canonical Wnt signaling is central to normal bone homeostasis, and secretion of
      Wnt signaling inhibitors by multiple myeloma (MM) cells contributes to MM-related
      bone resorption and disease progression. The aim of this study was to test the
      effect of Wnt3a on bone disease and growth of MM cells in vitro and in vivo.
      Although Wnt3a activated canonical signaling in the majority of MM cell lines and
      primary cells tested, Wnt3a had no effect on MM cell growth in vitro. Moreover,
      forced expression of Wnt3a in H929 MM cells conferred no growth advantage over
      empty vector-transfected cells in vitro or importantly when grown subcutaneously
      in severe combined immunodeficient (SCID) mice. Importantly, although H929 cells
      stably expressing an empty vector injected into human bone grew rapidly and
      induced a marked reduction in bone mineral density, bones engrafted with Wnt3a
      expressing H929 cells were preserved, exhibited increased osteoblast-to
      osteoclast ratios, and reduced tumor burden. Likewise, treatment of myelomatous
      SCID-hu mice, carrying primary disease, with recombinant Wnt3a stimulated bone
      formation and attenuated MM growth. These results provide further support of the
      potential anabolic and anti-MM effects of enhancing Wnt signaling in the bone.

PMID- 18344427
TI  - Scintigraphic detection of 125I seeds after permanent brachytherapy for prostate
      cancer.
AB  - The purpose of this investigation was to monitor the localization and migration
      of 125I seeds after permanent brachytherapy for prostate cancer using a new
      scintigraphic technique that may overcome the drawbacks of conventional x-ray
      methods. METHODS: 125I seeds emit gamma-rays with an average energy peak of 28
      keV. We used a gamma-camera equipped with low-energy high-resolution collimators
      that were tuned to an energy level of 35 keV with a 70% window width. Sixteen
      patients with prostate cancer were examined after 125I seed insertion. The number
      of seeds remaining in the prostate was confirmed using pelvic CT for
      postoperative dose planning; however, seeds that had migrated outside the
      prostate could not be detected. Furthermore, the migrated seeds were not
      completely traceable using chest or abdominal radiography. Thus, we adopted a
      scintigraphic technique to perform this task. The evaluation of radiography and
      scintigraphy findings was masked, and the rates of migrated seed detection were
      statistically examined using the McNemar test. To localize the migrated seeds, we
      fused the scintigraphic images of the migrated seeds and the patients' contours.
      RESULTS: Scintigraphy was successfully used to detect 20 migrated seeds of a
      total of 1,182 implanted seeds, whereas radiography was successfully used to
      detect 7. The sensitivity of the scintigraphy results was 20 of 20 (100%),
      whereas that of the radiography results was 7 of 20 (35%). Seed migration was
      detected in 11 of 16 patients (69%) using scintigraphy, whereas seed migration
      was detected in only 4 patients (25%) using radiography; this difference was
      statistically significant (P = 0.016). CONCLUSION: Scintigraphy is more effective
      for detecting seed migration and monitoring the localization of 125I seeds than
      radiography. The precise anatomic location of migrated seeds can be pinpointed
      using fusion images. Scintigraphy may become a standard procedure for monitoring
      seed migration during 125I brachytherapy in patients with prostate cancer.

PMID- 18344428
TI  - Reducing the incidence of 131I-induced sialadenitis: the role of pilocarpine.
AB  - The goal of this study was to reduce the salivary symptoms of pain and xerostomia
      caused by 131I therapy for papillary and follicular thyroid carcinoma. METHODS:
      In a single-blind controlled prospective study of 60 patients, we investigated
      whether pilocarpine, 5 mg orally every 8 h for 1 wk after 131I therapy, would
      reduce salivary symptoms. All patients received 8 mg of dexamethasone and 100 mg
      of dolasetron mesylate orally 2 h before therapy and every 12 h for another 5
      doses after 131I ingestion. In addition, for a week after therapy all drank 2,400
      mL of nondairy liquid per day and had sugar-free gum or candy in their mouths at
      all times when awake for a week and, for the first 3 nights, every 3 h after
      retiring. All brushed their mouths out every 3 h while awake and also for the
      first 3 nights after 131I therapy. Symptoms and signs were followed by frequent
      telephone calls over the first week and every 8-12 wk thereafter, a physical
      examination within the first 10 d after therapy, and a clinic visit 6-8 mo after
      therapy. Statistical comparisons were by chi2 analysis. RESULTS: The 2 patient
      groups were not statistically different in age, sex, type of thyroid cancer, or
      131I activity administered (P > 0.05). There were no statistical differences
      between the groups in the prevalence of sialadenitis, stomatitis, xerostomia, or
      dysgeusia over the next 6 mo (P > 0.05). CONCLUSION: Under the conditions of the
      study, pilocarpine did not reduce the occurrence of radiation sialadenitis or
      stomatitis. The occurrence, however, was lower than had previously been reported
      in the literature, possibly because of the concurrent stringent application of
      physiologic sialogogues (candy, gum, fluids), dexamethasone, and dolasetron
      mesylate, a serotonin receptor antagonist.

PMID- 18344429
TI  - Pemetrexed improves tumor selectivity of 111In-DTPA-folate in mice with folate
      receptor-positive ovarian cancer.
AB  - Folate-based radiopharmaceuticals can be used as imaging agents and for potential
      radiotherapy of folate receptor (FR)-positive malignant tissue (e.g., ovarian
      carcinomas). However, substantial FR expression in the kidneys results in
      undesired renal retention of radioactivity. Recently, we found that the
      preinjection of an antifolate significantly improved tumor selectivity of
      organometallic 99mTc-radiofolates in mice. The aim of this study was to
      corroborate the effect of pemetrexed with the clinically tested 111In-DTPA-folate
      (DTPA is diethylenetriaminepentaacetic acid) in a human ovarian cancer
      xenografted mouse model. METHODS: In vivo studies were performed in female
      athymic nude mice bearing subcutaneous FR-positive ovarian tumors (IGROV-1 and
      SKOV-3) or metastases (after intraperitoneal SKOV-3 cell inoculation).
      Biodistribution studies were performed 1, 4, and 24 h after administration of
      111In-DTPA-folate (0.7 MBq/mouse, 0.35 mug) with or without preinjection of
      pemetrexed (PMX, 400 microg) 1 h before the radiofolate. Images were acquired
      with a high-resolution, high-sensitivity SPECT/CT camera, 4 and 24 h after
      injection of the radiotracer (30-50 MBq/mouse, 4.5-10 microg). RESULTS: In
      biodistribution studies the tumor uptake of 111In-DTPA-folate (IGROV-1: 9.79 +/-
      3.21 %ID/g [percentage injected dose per gram]; SKOV-3: 7.57 +/- 0.61 %ID/g, 4 h
      after injection) was high and retained over the time of investigation. However,
      considerable retention of radioactivity was found in kidneys (85-105 %ID/g, 4 h
      after injection), resulting in unfavorably low tumor-to-kidney ratios (
      approximately 0.10). Preinjection of PMX resulted in a significant reduction of
      renal uptake (20%-30% of control values, P < 0.03) at all time points after
      injection of 111In-DTPA-folate, whereas the tumor uptake was retained. Thus, the
      tumor-to-kidney ratio was significantly increased to approximately 0.50. SPECT/CT
      images confirmed the superior tumor-to-background ratio in mice injected with
      PMX. These findings were particularly evident in mice with SKOV-3 metastases that
      could be visualized only when 111In-DTPA-folate was administered in combination
      with PMX. CONCLUSION: The application of PMX resulted in a significant reduction
      of undesired radioactivity accumulation in kidneys, whereas the tumor uptake
      remained unaffected. These observations suggest a general validity of the
      reducing effect of PMX on the uptake of radiofolates in kidneys. Our findings
      will lead the way toward the development of folate-based radiotherapy.

PMID- 18344430
TI  - PET image denoising using a synergistic multiresolution analysis of structural
      (MRI/CT) and functional datasets.
AB  - PET allows the imaging of functional properties of the living tissue, whereas
      other modalities (CT, MRI) provide structural information at significantly higher
      resolution and better image quality. Constraints for injected radioactivity,
      technologic limitations of current instrumentation, and inherent spatial
      uncertainties on the decaying process affect the quality of PET images. In this
      article we illustrate how structural information of matched anatomic images can
      be used in a multiresolution model to enhance the signal-to-noise ratio of PET
      images. The model states a flexible relation between function and structure in
      the brain and replaces high-resolution information of PET images with
      appropriately scaled MRI or CT local detail. The method can be naturally extended
      to other functional imaging modalities (SPECT, functional MRI). METHODS: The
      methodology is based on the multiresolution property of the wavelet transform
      (WT). First, the coregistered structural image (MRI/CT) is downgraded to the
      resolution of the PET volume through appropriate filtering. Second, a redundant
      version of the WT is applied to both volumes. Third, a linear model is applied to
      the set of local coefficients of both image volumes and resulting parameters are
      recorded. The overall set of linear coefficients is then modeled as a mixture of
      multivariate gaussian distributions and fitted through a k-means algorithm.
      Finally, the local wavelet coefficients of the PET image are substituted by the
      corresponding values of the MRI/CT set calibrated according to the resulting
      clustering. The methodology was validated on digital simulated images and
      clinical data to evaluate its quantitative potential for individual as well as
      group analysis. RESULTS: Application to real and simulated datasets shows very
      effective noise reduction (15% SD) while resolution is preserved. CONCLUSION: The
      methodology is robust to errors in the coregistration parameters, practical to
      implement, and computationally fast.

PMID- 18344431
TI  - In vitro evaluation of radioprotective and radiosensitizing effects of rituximab.
AB  - Clinical radioimmunotherapies with anti-CD20 monoclonal antibodies involve
      administering a predose of unlabeled anti-CD20 antibodies to favorably alter the
      biodistribution profile of the subsequently administered radiolabeled antibodies
      and mediate antitumor effects. Prior in vitro data suggested that unlabeled anti
      CD20 monoclonal antibodies radiosensitize lymphoma cells as well. We assessed the
      antiproliferative and possible radiosensitizing capabilities of an anti-CD20
      monoclonal antibody, rituximab. METHODS: Luciferase-transfected (via a lentivirus
      vector) CD20+ human Raji lymphoma cells in log-phase growth were incubated with
      or without rituximab (20 microg/mL) for either 1 or 24 h before external-beam
      radiation exposure. Cell counts were measured with a luciferase assay at 24-h
      intervals. Subsets of these cells were also analyzed for cell cycle status by
      flow cytometry. RESULTS: Rituximab pretreatment and irradiation were found to
      significantly inhibit tumor cell growth compared with irradiation alone (by a
      factor of 0.40 at 1 Gy [P < 0.01]). One hour of rituximab pretreatment modestly
      radiosensitized tumor cells at a radiation dose of 1 Gy (by a factor of 1.03
      compared with the results for nonirradiated cells). At higher radiation doses (2
      and 12 Gy), 1 h of rituximab pretreatment paradoxically radioprotected tumor
      cells by factors of 0.25 (P < 0.01) and 0.54 (P < 0.05), respectively. Rituximab
      predosing for 24 h was found to be radiosensitizing at a radiation dose of 4 Gy
      (by a factor of 2.84 [P < 0.01]) but radioprotective at radiation doses of 1, 8,
      and 12 Gy (by factors of 0.10 [P < 0.01], 2.50 [P < 0.01], and 2.07 [P < 0.05],
      respectively). These results correlated with retardation of the cell cycle at 6 d
      after rituximab administration, as determined by flow cytometry. CONCLUSION:
      Rituximab demonstrated a direct tumor antiproliferative effect in the absence of
      radiation. At lower levels of radiation exposure, rituximab radiosensitized Raji
      lymphoma cells. At higher doses of radiation, rituximab paradoxically protected
      tumor cells against ionizing radiation, possibly through effects on the cell
      cycle. These radiobiologic effects of rituximab should be carefully considered in
      the design of radioimmunotherapeutic trials.

PMID- 18344432
TI  - Effect of progenitor cells on myocardial perfusion and metabolism in patients
      after recanalization of a chronically occluded coronary artery.
AB  - Even after recanalization of a chronic total coronary occlusion, functional
      recovery is incomplete and parts of the myocardium remain hypoperfused. In this
      randomized, placebo-controlled, and double-blinded study, we investigated
      relative changes in myocardial perfusion and glucose metabolism induced by
      intracoronary administration of blood-derived circulating progenitor cells
      (CPCs), compared with the natural course in a control group after recanalization
      of total coronary occlusion. METHODS: After recanalization of total coronary
      occlusion, 26 patients were randomly assigned to the CPC treatment or placebo
      group. Regional myocardial perfusion and glucose metabolism were assessed by
      99mTc-tetrofosmin SPECT and 18F-FDG PET at baseline (after recanalization of
      total coronary occlusion) and 3 mo after the administration of 69 +/- 14 x 10(6)
      CPCs or cell-free serum, respectively. Segments were classified as "normal,"
      "perfusion-metabolism mismatch" (dysfunctional segments with a 99mTc-tetrofosmin
      18F-FDG mismatch), or "scar." RESULTS: In contrast to the placebo group, CPC
      administration resulted in a significant decrease in the number of segments with
      a perfusion-metabolism mismatch, from 3.0 +/- 0.5 to 1.7 +/- 0.6 segments (P <
      0.05 vs. baseline). Of the normal segments at baseline, 2.7% in the CPC group and
      30% in the placebo group revealed a perfusion-metabolism mismatch at follow-up
      after 3 mo (P < 0.05 vs. placebo). CONCLUSION: Intracoronary administration of
      CPCs significantly reduces the amount of myocardium with a perfusion-metabolism
      mismatch and prevents areas with normal perfusion and metabolism after
      recanalization of total coronary occlusion from becoming dysfunctional during the
      next 3 mo. These results show that PET and SPECT can be used to monitor the
      effect of progenitor cells on myocardial integrity. More important, they provide
      evidence supporting expansion of the use of progenitor cell treatment to chronic
      coronary artery disease.

PMID- 18344433
TI  - Imaging of HSV-tk Reporter gene expression: comparison between [18F]FEAU,
      [18F]FFEAU, and other imaging probes.
AB  - Herpes virus type 1 thymidine kinase (HSV1-tk) and the mutant HSV1-sr39tk are the
      2 most widely used "reporter genes" for radiotracer-based imaging. Two pyrimidine
      nucleoside analogs, [18F]FEAU (1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)-5
      ethyluridine) and [18F]FFEAU (1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)-5-(2
      fluoroethyl)uridine), have generated recent interest as potential new probes for
      imaging HSV1-tk and HSV1-sr39tk gene expression. METHODS: We compared [18F]FEAU
      and [18F]FFEAU with a series of other pyrimidine nucleoside derivatives
      (including 1-(2'-deoxy-2'-fluoro-beta-d-arabinofuranosyl)-5-iodouridine [FIAU])
      and with acycloguanosine analogs using a stable HSV1-tk transduced cell line
      (RG2TK+) and wild-type RG2 cells. RESULTS: The in vitro accumulation data and the
      calculated and normalized clearance constant, nKi, as well as sensitivity and
      selectivity indices indicated that 2 pyrimidine nucleoside probes, [18F]FEAU and
      [18F]FFEAU, had the best uptake characteristics. These probes were selected for
      further dynamic PET studies in nude rats bearing subcutaneous RG2TK+ and RG2
      tumors. The 2-h postinjection [18F]FEAU uptake levels were 3.3% +/- 1.0% and
      0.28% +/- 0.07% dose/cm3 in subcutaneous RG2TK+ and RG2 tumors, respectively, and
      2.3% +/- 0.2% and 0.19% +/- 0.01% dose/cm3, respectively, for [18F]FFEAU. The
      corresponding RG2TK+/RG2 uptake ratios were 11.5 +/- 1.5 and 12.2 +/- 1.4,
      respectively. The inherent problem of comparing different radiolabeled pyrimidine
      nucleoside and guanosine-based probes for imaging HSV1-tk expression using
      different transduced cell lines and assay systems in the absence of an
      independent thymidine kinase-enzyme assay is discussed. CONCLUSION: For HSV1-tk
      reporter systems that require a 1- to 4-h PET paradigm, HSV1-tk-[18F]FEAU is the
      current top contender.

PMID- 18344434
TI  - Estimation of the beta+ dose to the embryo resulting from 18F-FDG administration
      during early pregnancy.
AB  - Although 18F-FDG examinations are widely used, data are lacking on the dose to
      human embryo tissues in cases of exposure in early pregnancy. Although the photon
      component can easily be estimated from available data on the pharmacokinetics of
      18F-FDG in female organs and from phantom measurements (considering the uterus as
      the target organ), the intensity of embryo tissue uptake, which is essential for
      deriving the beta+ dose, is not known. We report the case of a patient who
      underwent 18F-FDG PET/CT for tumor surveillance and who was later found to have
      been pregnant at the time of the examination (embryo age, 8 wk). METHODS: The
      patient received 320 MBq of (18)F-FDG. Imaging started with an unenhanced CT scan
      1 h after the injection, followed by PET acquisition. PET images were used to
      compute the total number of beta+ emissions in embryo tissues per unit of
      injected activity, from standardized uptake value (SUV) measurements corrected
      for partial-volume effects. A Monte Carlo track structure code was then used to
      derive the beta+ self-dose and the beta+ cross-dose from amniotic fluid. The
      photon and CT doses were added to obtain the final dose received by the embryo.
      RESULTS: The mean SUV in embryo tissues was 2.7, after correction for the partial
      volume effect. The mean corrected SUV of amniotic fluid was 1.1. Monte Carlo
      simulation showed that the beta+ dose to the embryo (self-dose plus cross-dose
      from amniotic fluid) was 1.8E-2 mGy per MBq of injected 18F-FDG. Based on MIRD
      data for the photon dose to the uterus, the estimated photon dose to the embryo
      was 1.5E-2 mGy/MBq. Thus, the specific 18F-FDG dose to the embryo was 3.3E-2
      mGy/MBq (10.6 mGy in this patient). The CT scan added a further 8.3 mGy.
      CONCLUSION: The dose to the embryo is 3.3E-2 mGy/MBq of 18F-FDG. The beta+ dose
      contributes 55% of the total dose. This value is higher than previous estimates
      in late nonhuman-primate pregnancies.

PMID- 18344435
TI  - 11C-loperamide and its N-desmethyl radiometabolite are avid substrates for brain
      permeability-glycoprotein efflux.
AB  - Loperamide, an opiate receptor agonist, does not cross the blood-brain barrier
      because it is a substrate for the permeability-glycoprotein (P-gp) efflux pump.
      We evaluated 11C-loperamide as a PET radiotracer to measure P-gp function in
      vivo. METHODS: Monkeys were injected with 11C-loperamide, and PET brain images
      were acquired for 120 min. The baseline scans were followed by scans acquired
      after administration of either of 2 P-gp inhibitors, (2R)-anti-5-{3-[4-(10,11
      dichloromethanodibenzo-suber-5-yl)piperazin-1-yl]-2-hydroxypropoxy}quinoline
      trihydrochloride (DCPQ) or tariquidar. Both the PET scans and ex vivo
      measurements were obtained in P-gp knockout and wild-type mice. RESULTS:
      Pharmacologic inhibition of P-gp in monkeys dose-dependently increased brain
      activity, with a 3.7-fold effect at the highest DCPQ dose (8 mg/kg
      intravenously). This increase of brain activity was not caused peripherally,
      because DCPQ insignificantly changed the plasma concentration and plasma protein
      binding of radiotracer. Furthermore, the structurally dissimilar inhibitor,
      tariquidar, also increased brain uptake with potency equal to that of DCPQ. P-gp
      knockout mice had 3-fold higher brain activity on PET than did wild-type animals.
      Four radiometabolites were detected in the plasma and brains of ex vivo mice. The
      most lipophilic radiometabolite was found to be comobile with reference dLop on
      high-performance liquid chromatography. The brain concentrations of 11C
      loperamide and the putative 11C-dLop were about 16-fold greater in P-gp knockout
      mice than in wild-type mice. CONCLUSION: Both 11C-loperamide and its putative
      radiometabolite 11C-dLop are avid P-gp substrates. 11C-dLop may be superior to
      11C-loperamide in measuring P-gp function at the blood-brain barrier, because
      further demethylation of 11C-dLop will generate radiometabolites that have little
      entry into the brain.

PMID- 18344436
TI  - Tumor blood flow measured by PET dynamic imaging of first-pass 18F-FDG uptake: a
      comparison with 15O-labeled water-measured blood flow.
AB  - PET molecular imaging of 15O-labeled water is the gold standard for measuring
      blood flow in humans. However, this requires an on-site cyclotron to produce the
      short-lived 15O tracer, which is cost-prohibitive for most clinical PET centers.
      The purpose of this study was to determine if the early uptake of 18F-FDG could
      be used to measure regional blood flow in tumors in the absence of 15O-water.
      METHODS: PET scans were obtained in patients being evaluated for tumor perfusion
      and glucose metabolism in a phase I dose-escalating protocol for endostatin, a
      novel antiangiogenic agent. A 2-min perfusion scan was performed with a bolus
      injection of 2,220 MBq (60 mCi) of 15O-water, which was followed by a 370-MBq (10
      mCi) dose of 18F-FDG. Four sequential scans of 18F-FDG uptake were acquired,
      consisting of an early 2-min uptake scan-or first-pass scan-and 3 sequential 15
      min late 18F-FDG uptake scans. Regions of interest (ROIs) were drawn on 2 or more
      tumor sites and on back muscle, as a control ROI, for each patient. Arterial
      blood concentration was derived from the PET scans by drawing an ROI over a large
      artery in the field of view. Blood flow was computed with a simple 1-compartment
      blood flow model using the first 2 min of data after injection. RESULTS: Blood
      flow estimated from the early uptake of 18F-FDG was linearly correlated with 15O
      measured blood flow, with an intercept of 0.01, a slope of 0.86, and an R2
      regression coefficient of 0.74 (r = 0.86). The 18F-FDG tumor extraction fraction
      relative to 15O-water averaged 0.86. A preliminary case study of a patient with
      prostate cancer confirms the utility of the first-pass 18F-FDG blood flow
      analysis in tumor diagnosis. CONCLUSION: These results suggest that the first
      pass uptake of 18F-FDG may provide an estimate of perfusion in a tumor within the
      limitations of incomplete extraction of 18F-FDG compared with 15O-water.

PMID- 18344437
TI  - Intratumoral spatial distribution of hypoxia and angiogenesis assessed by 18F
      FAZA and 125I-Gluco-RGD autoradiography.
AB  - The hypoxia-inducible factor-1 alpha (HIF-1 alpha) activates angiogenesis in
      response to cellular hypoxia, suggesting a spatial correlation between
      angiogenesis and tissue hypoxia. METHODS: Using digital autoradiography of
      coinjected 18F-labeled azomycin arabinoside (8F-FAZA) (assessing regional
      hypoxia) and a glycosylated RGD-containing peptide (125I-3-iodo-dTyr(4)-cyclo(
      Arg-Gly-Asp-dTyr-Lys(SAA)-), or 125I-Gluco-RGD) (assessing angiogenesis via
      binding to alpha v beta 3 integrin receptors on endothelial cells) performed on
      22 EMT6 tumor xenografts, we investigated the intratumoral spatial distribution
      of these tracers. We applied a Bayesian bivariate image analysis using the mean
      tumor-to-muscle ratio as a discriminator, resulting in 4 groups: FAZA high/RGD
      high (Q1), FAZA low/RGD high (Q2), FAZA low/RGD low (Q3), and FAZA high/RGD low
      (Q4). In an additional 18 xenografts, the immunohistochemically derived HIF-1
      alpha protein distribution was compared with 18F-FAZA autoradiography. Animals
      were divided into groups breathing either room air or carbogen (95% oxygen, 5%
      CO2) for 4 h until sacrifice. RESULTS: Under room air conditions, roughly 60% of
      the tumor surface displayed a spatial coupling of 18F-FAZA and 125I-Gluco-RGD
      uptake: either high (Q1) or low (Q3) uptake for both tracers, with Q1 indicating
      spatial association of hypoxia and angiogenesis and Q3 indicating adequate
      oxygenation without active angiogenesis. However, the remaining approximately 40%
      of the tumor surface showed discordant 18F-FAZA and 125I-Gluco-RGD uptake,
      indicating that hypoxia and angiogenesis are not necessarily spatially linked to
      each other and highlighting substantial intratumoral heterogeneity of the 18F
      FAZA and 125I-Gluco-RGD uptake. Although carbogen breathing conditions
      significantly decreased the mean 18F-FAZA tumor-to-muscle ratio, no significant
      changes were observed for 125I-Gluco-RGD, indicating that an acute increase in
      tumor oxygenation did not influence alpha v beta 3 integrin receptor expression.
      The HIF-1 alpha-positive (HIFpos) tumor cell fraction was not significantly
      influenced by breathing conditions and covered between 0% and 35% of the total
      tumor section surface. However, the HIFpos tumor section surface was much smaller
      than the tumor section surface of increased 18F-FAZA uptake, suggesting that both
      markers are identifying distinctly different biologic processes associated with
      hypoxia. CONCLUSION: The study revealed a substantial spatial discordance of the
      18F-FAZA and 125I-Gluco-RGD tumor distribution suggesting that hypoxia and
      angiogenesis are not necessarily spatially linked in malignancies. These results
      may prove essential in developing advanced targeted systemic chemotherapeutic
      approaches (such as combinations of hypoxia-activated cytotoxins and
      antiangiogenic drugs) for hypoxic tumors.

PMID- 18344438
TI  - Spillover and partial-volume correction for image-derived input functions for
      small-animal 18F-FDG PET studies.
AB  - We present and validate a method to obtain an input function from dynamic image
      data and 0 or 1 blood sample for small-animal 18F-FDG PET studies. The method
      accounts for spillover and partial-volume effects via a physiologic model to
      yield a model-corrected input function (MCIF). METHODS: Image-derived input
      functions (IDIFs) from heart ventricles and myocardial time-activity curves were
      obtained from 14 Sprague-Dawley rats and 17 C57BL/6 mice. Each MCIF was expressed
      as a mathematic equation with 7 parameters, which were estimated simultaneously
      with the myocardial model parameters by fitting the IDIFs and myocardium curves
      to a dual-output compartment model. Zero or 1 late blood sample was used in the
      simultaneous estimation. MCIF was validated by comparison with input measured
      from blood samples. Validation included computing errors in the areas under the
      curves (AUCs) and in the 18F-FDG influx constant Ki in 3 types of tissue.
      RESULTS: For the rat data, the AUC error was 5.3% +/- 19.0% in the 0-sample MCIF
      and -2.3% +/- 14.8% in the 1-sample MCIF. When the MCIF was used to calculate the
      Ki of the myocardium, brain, and muscle, the overall errors were -6.3% +/- 27.0%
      in the 0-sample method (correlation coefficient r = 0.967) and 3.1% +/- 20.6% in
      the 1-sample method (r = 0.970). The t test failed to detect a significant
      difference (P > 0.05) in the Ki estimates from both the 0-sample and the 1-sample
      MCIF. For the mouse data, AUC errors were 4.3% +/- 25.5% in the 0-sample MCIF and
      -1.7% +/- 20.9% in the 1-sample MCIF. Ki errors averaged -8.0% +/- 27.6% for the
      0-sample method (r = 0.955) and -2.8% +/- 22.7% for the 1-sample method (r =
      0.971). The t test detected significant differences in the brain and muscle in
      the Ki for the 0-sample method but no significant differences with the 1-sample
      method. In both rat and mouse, 0-sample and 1-sample MCIFs both showed at least a
      10-fold reduction in AUC and Ki errors compared with uncorrected IDIFs.
      CONCLUSION: MCIF provides a reliable, noninvasive estimate of the input function
      that can be used to accurately quantify the glucose metabolic rate in small
      animal 18F-FDG PET studies.

PMID- 18344439
TI  - Value and limitations of target-vessel ischemia in predicting late clinical
      events after drug-eluting stent implantation.
AB  - Drug-eluting stents reduce clinical events related to restenosis but may be
      complicated by late stent-thrombosis. Whereas assessment of target-vessel
      ischemia by myocardial perfusion scintigraphy identifies relevant restenosis
      noninvasively, it is unknown whether this technique may also predict late
      clinical events related to late stent-thrombosis and to restenosis after drug
      eluting stent implantation. METHODS: All 826 patients treated with stenting
      between May 2003 and May 2004 were included in the Basel Stent Cost Effectiveness
      Trial (Basel Stent Kosten-Effektivitats Trial, or BASKET) and randomized (2:1) to
      drug-eluting stents or bare metal stents. Myocardial scintigraphy was performed
      on 476 (64%) of 747 patients without major events after 6 mo. Patients were
      followed for 1 y for cardiac death, nonfatal myocardial infarction, and target
      vessel revascularization due to restenosis or late stent-thrombosis. RESULTS: The
      rate of target-vessel ischemia in these patients was lower with drug-eluting
      stents than with bare metal stents (5.4% vs. 10.4%, P = 0.045), similar to the
      rates of symptom-driven target-vessel revascularization up to 6 mo (4.6% vs.
      7.8%, P = 0.08). Ischemia was silent in 68%. During follow-up, patients with
      target-vessel ischemia had higher event rates than did patients without ischemia
      (32.4% vs. 6.1%, P < 0.001); however, ischemia did not predict late stent
      thrombosis (0/11 cases). CONCLUSION: The rate of clinical restenosis assessed
      scintigraphically was lower with drug-eluting stents than with bare metal stents
      and paralleled that of symptom-driven target-vessel revascularization. Target
      vessel ischemia independently predicted late clinical events related to
      restenosis but not to late stent-thrombosis.

PMID- 18344440
TI  - Clinical utility of 18F-FDG PET/CT in assessing the neck after concurrent
      chemoradiotherapy for Locoregional advanced head and neck cancer.
AB  - For patients with locoregional advanced head and neck squamous cell carcinoma
      (HNSCC), concurrent chemoradiotherapy is a widely accepted treatment, but the
      need for subsequent neck dissection remains controversial. We investigated the
      clinical utility of 18F-FDG PET/CT in this setting. METHODS: In this
      Institutional Review Board (IRB)-approved and Health Insurance Portability and
      Accountability Act (HIPPA)-compliant retrospective study, we reviewed the records
      of patients with HNSCC who were treated by concurrent chemoradiation therapy
      between March 2002 and December 2004. Patients with lymph node metastases who
      underwent 18F-FDG PET/CT > or = 8 wk after the end of therapy were included. 18F
      FDG PET/CT findings were validated by biopsy, histopathology of neck dissection
      specimens (n = 18), or clinical and imaging follow-up (median, 37 mo). RESULTS:
      Sixty-five patients with a total of 84 heminecks could be evaluated. 18F-FDG
      PET/CT (visual analysis) detected residual nodal disease with a sensitivity of
      71%, a specificity of 89%, a positive predictive value (PPV) of 38%, a negative
      predictive value (NPV) of 97%, and an accuracy of 88%. Twenty-nine heminecks
      contained residual enlarged lymph nodes (diameter, > or =1.0 cm), but viable
      tumor was found in only 5 of them. 18F-FDG PET/CT was true-positive in 4 and
      false-positive in 6 heminecks, but the NPV was high at 94%. Fifty-five heminecks
      contained no residual enlarged nodes, and PET/CT was true-negative in 50 of
      these, yielding a specificity of 96% and an NPV of 98%. Lack of residual
      lymphadenopathy on CT had an NPV of 96%. Finally, normal 18F-FDG PET/CT excluded
      residual disease at the primary site with a specificity of 95%, an NPV of 97%,
      and an accuracy of 92%. CONCLUSION: In patients with HNSCC, normal 18F-FDG PET/CT
      after chemoradiotherapy has a high NPV and specificity for excluding residual
      locoregional disease. In patients without residual lymphadenopathy, neck
      dissection may be withheld safely. In patients with residual lymphadenopathy, a
      lack of abnormal 18F-FDG uptake in these nodes also excludes viable tumor with
      high certainty, but confirmation of these data in a prospective study may be
      necessary before negative 18F-FDG PET/CT may become the only, or at least most
      decisive, criterion in the management of the neck after chemoradiotherapy.

PMID- 18344441
TI  - 6-L-18F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors: basic aspects
      and emerging clinical applications.
AB  - In recent years, 6-l-18F-fluorodihydroxyphenylalanine (18F-DOPA) PET has emerged
      as a new diagnostic tool for the imaging of neuroendocrine tumors. This
      application is based on the unique property of neuroendocrine tumors to produce
      and secrete various substances, a process that requires the uptake of metabolic
      precursors, which leads to the uptake of 18F-DOPA. This nonsystematic review
      first describes basic aspects of 18F-DOPA imaging, including radiosynthesis,
      factors involved in tracer uptake, and various aspects of metabolism and imaging.
      Subsequently, this review provides an overview of current clinical applications
      in neuroendocrine tumors, including carcinoid tumors, pancreatic islet cell
      tumors, pheochromocytoma, paraganglioma, medullary thyroid cancer,
      hyperinsulinism, and various other clinical entities. The application of PET/CT
      in carcinoid tumors has unsurpassed sensitivity. In medullary thyroid cancer,
      pheochromocytoma, and hyperinsulinism, results are also excellent and contribute
      significantly to clinical management. In the remaining conditions, the initial
      experience with 18F-DOPA PET indicates that it seems to be less valuable, but
      further study is required.

PMID- 18344442
TI  - Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide
      transporter.
AB  - H+/peptide transporter, PEPT1, is functionally expressed in some human cancer
      cell lines and might be a candidate molecular target for detection of cancers in
      vivo using PET. The aim of the present study was to establish a novel tumor
      imaging technology using a PET tracer targeted to H+/peptide transporter(s). We
      also compared the tracer with 18F-FDG, focusing on the specificity of their
      accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET
      tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into
      athymic mice transplanted with human pancreatic, prostate, and gastric cancer
      cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing
      mice, and in mice with inflammatory tissue, were assessed by imaging with a
      positron planar imaging system (PPIS). Tissue distributions of tracer
      radioactivity were also measured. The expression levels of PEPT1 and PEPT2
      (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by
      immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58
      available cancer cell lines were quantified by means of real-time polymerase
      chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the
      PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was
      confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of
      11C-Gly-Sar increased in a time-dependent manner and were much higher than unity.
      Most of the radioactivity found in the tumor tissue was recovered as the intact
      tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in
      tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in
      inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG
      was highly accumulated, with the values of the selectivity index being >25.1 and
      0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were
      expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in
      the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a
      promising tumor-imaging agent and is superior to 18F-FDG for distinguishing
      between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed
      in various types of tumor cells examined, 11C-Gly-Sar could be useful for the
      detection of many types of cancers.

PMID- 18344443
TI  - Modeling considerations for 11C-CUMI-101, an agonist radiotracer for imaging
      serotonin 1A receptor in vivo with PET.
AB  - Several lines of evidence demonstrate involvement of serotonin 1A receptors (5
      HT1ARs) in the pathophysiology of neuropsychiatric disorders such as depression,
      suicidal behavior, schizophrenia, and Alzheimer's disease. We recently published
      the synthesis and initial evaluation of [O-methyl-11C]2-(4-(4-(2
      methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione (11C
      MMP), a 5-HT1AR agonist. Here we determine the optimal modeling parameters for
      11C-MMP under its new name, 11C-CUMI-101, in Papio anubis. METHODS: PET scans
      were performed on 2 adult male P. anubis; 166.5 MBq +/- 43.0 (4.50 +/- 1.16 mCi)
      of 11C-CUMI-101 were injected as an intravenous bolus, and emission data were
      collected for 120 min in 3-dimensional mode. We evaluated 4 different models (1-
      and 2-tissue compartment iterative and noniterative kinetic models, basis
      pursuit, and likelihood estimation in graphical analysis [LEGA]), using binding
      potential (BPF = Bmax/Kd) (Bmax = maximum number of binding sites; Kd =
      dissociation constant) as the outcome measure. Arterial blood sampling and
      metabolite-corrected arterial input function were used for full quantification of
      BPF. To assess the performance of each model, we compared results using 6
      different metrics (percentage difference, within-subject mean sum of squares
      [WSMSS] for reproducibility; variance across subjects, intraclass correlation
      coefficient [ICC] for reliability; identifiability based on bootstrap resampling
      of residuals; and time stability analysis to determine minimal required scanning
      time) at each of 6 different scanning durations. Models were also evaluated on
      scans acquired after injecting the 5-HT1A antagonist [N-(2-(4-(2-methoxyphenyl)-1
      piperazinyl)ethyl)-N-(2-pyridinyl) cyclohexane carboxamide] [WAY100635] 0.5
      mg/kg, intravenous) and the 5-HT1A agonist 8-hydroxy-2-(di-n
      propylamino)tetralin) [8-OH-DPAT] 2 mg/kg, intravenous). RESULTS: All metabolites
      are more polar than 11C-CUMI-101, and no significant change in metabolites was
      observed in the blocking studies. The free fraction is 59% +/- 3%. We determined
      that 100 min of scanning time is adequate and that for the region-of-interest
      (ROI)-level analysis, the LEGA model gives the best results. The median test
      retest percentage difference for BPF is 11.15% +/- 4.82% across all regions,
      WSMSS = 2.66, variance = 6.07, ICC = 0.43, and bootstrap identifiability = 0.59.
      Preadministration of WAY100635 and 8-OH-DPAT resulted in 87% and 76% average
      reductions in BPF values, respectively, across ROIs. CONCLUSION: On the basis of
      the measurable free fraction, high affinity and selectivity, adequate blood-brain
      permeability, and favorable plasma and brain kinetics, 11C-CUMI-101 is an
      excellent candidate for imaging high-affinity 5-HT1ARs in humans.

PMID- 18344444
TI  - Quantitative measures of coronary stenosis severity by 64-Slice CT angiography
      and relation to physiologic significance of perfusion in nonobese patients:
      comparison with stress myocardial perfusion imaging.
AB  - Coronary stenosis severity by 64-slice CT angiography (CTA) is acceptably
      correlated with intravascular ultrasound. Stress myocardial perfusion imaging
      using SPECT is an established method for assessment of the functional
      significance of coronary stenosis. Our aim was to assess a clinical validation of
      quantitative measurements of coronary stenosis severity by 64-slice CTA and the
      relation to the physiologic significance of myocardial perfusion. METHODS: One
      hundred four patients with suspected coronary artery disease underwent 64-slice
      CTA and stress 201Tl SPECT. The stenosis severities of 105 coronary lesions
      assessed by CTA with sufficient image quality were compared with the results of
      stress 201Tl SPECT. The body mass index (BMI) of the patients was 23.8 kg/m2
      (range, 21.1-25.6 kg/m2). RESULTS: Reversible defects began to increase
      progressively when the area of stenosis was at least 60%, and the prevalence of
      these reversible defects and their severity significantly increased as the degree
      of stenosis increased. When stenosis severity by CTA is < 60%, ischemia is seldom
      observed; when stenosis severity is > or =80%, ischemia is common (86%). For
      intermediate stenosis severity values of 60%-70%, the prevalence of reversible
      defects was 9 of 27 vessels (33%), and for stenosis severity values of 70%-80%,
      the prevalence was 20 of 37 vessels (54%). When evaluating the diagnostic
      accuracy of stenosis severity by CTA to identify patients with ischemia excluding
      all nonevaluable vessels, applying stenosis thresholds of >70% results in 79%
      sensitivity, 92% specificity, 66% positive predictive value, and 96% negative
      predictive value. A lesion minimal luminal cross-sectional area of < 3.7 mm2 was
      a good accurate cutoff value for significant coronary narrowing using stress
      SPECT, with a sensitivity of 88% and specificity of 83% by receiver-operating
      characteristic analysis. CONCLUSION: Despite an excellent negative predictive
      value to rule out the presence of ischemia, 64-slice CTA alone is a poor
      discriminator of the functional significance of myocardial ischemia in a highly
      selected patient population with a low BMI.

PMID- 18344445
TI  - Genetic modifiers of retinal degeneration in the rd3 mouse.
AB  - PURPOSE: In previous studies of light-induced (LRD) and age-related (ageRD)
      retinal degeneration (RD) between the BALB/cByJ (BALB) and B6(Cg)-Tyr(c-2J)/J
      (B6a) albino mouse strains, RD-modifying quantitative trait loci (QTLs) were
      identified. After breeding BALB- and B6a-rd3/rd3 congenic strains and finding
      significant differences in RD, an F1 intercross to determine rd3 QTLs that
      influence this inherited RD was performed. METHODS: N10, F2 BALB- and B6a-rd3/rd3
      strains were measured for retinal outer nuclear layer (ONL) thickness from 5 to
      12 weeks of age. Since 10 weeks showed significant differences in the ONL, F2
      progeny from an F1 intercross were measured for ONL thickness. F2 DNAs were
      genotyped for SNPs by the Center for Inherited Disease Research. Correlation of
      genotype with phenotype was made with Map Manager QTX. RESULTS: One hundred forty
      eight SNPs approximately 10 cM apart were typed in the F2 progeny and analyzed.
      Significant QTLs were identified on chromosomes (Chrs) 17, 8, 14, and 6 (B6a
      alleles protective) and two on Chr 5 (BALB alleles protective). Suggestive QTLs
      were found as well. For the strongest QTLs, follow-up SNPs were analyzed to
      narrow the critical intervals. Additional studies demonstrated that rd3 disease
      is exacerbated by light but not protected by the absence of rhodopsin
      regeneration. CONCLUSIONS: QTLs were identified that modulate rd3-RD. These
      overlapped some QTLs from previous ageRD and LRD studies. The presence of some of
      the same QTLs in several studies suggests partial commonality in RD pathways.
      Identifying natural gene/alleles that modify RDs opens avenues of study that may
      lead to therapies for RD diseases.

PMID- 18344446
TI  - Carrier of R14W in carbonic anhydrase IV presents Bothnia dystrophy phenotype
      caused by two allelic mutations in RLBP1.
AB  - PURPOSE: Bothnia dystrophy (BD) is an autosomal recessive retinitis pigmentosa
      (arRP) associated with the c.700C>T mutation in the RLBP1 gene. Testing of
      patients with BD has revealed the c.700C>T mutation on one or both alleles. The
      purpose of this study was to elucidate the underlying genetic mechanisms along
      with a clinical evaluation of the heterozygous patients with BD. METHODS:
      Patients with BD heterozygous for the RLBP1 c.700C>T were tested for 848
      mutations by arrayed primer-extension technology. Further mutation detection was
      performed by PCR-restriction fragment length polymorphism (RFLP), sequencing,
      denaturing (d)HLPC and allelic discrimination. The ophthalmic examinations were
      performed in all c.700C>T heterozygotes. RESULTS: The clinical findings in 10 BD
      heterozygotes were similar to those in the homozygotes. The presence of a second
      mutation, c.677T>A, corresponding to p.M226K was detected in all 10 cases.
      Segregation analysis showed that the mutations were allelic, and the patients
      were compound heterozygotes [c.677T>A]+[c.700C>T]. One of those patients was also
      a carrier of the c.40C>T corresponding to the p.R14W change in carbonic anhydrase
      IV (CAIV) associated with autosomal dominant RP, RP17. His mother, a carrier of
      the identical change was declared healthy after ophthalmic examination. This
      sequence variant was found in 6 of 143 tested blood donors. CONCLUSIONS: The high
      frequency of arRP in northern Sweden is due to two mutations in the RLBP1 gene:
      c.677T>A and c.700C>T. BD is caused by the loss of CRALBP function due to changed
      physical features and impaired activity of retinoid binding. The CAIV p.R14W
      sequence variant found in one of the patients with a BD phenotype is a benign
      polymorphism in a population of northern Sweden.

PMID- 18344447
TI  - Resolution visual fields in children surgically treated for bilateral congenital
      cataract.
AB  - PURPOSE: To evaluate visual acuity (best corrected visual acuity) and peripheral
      sensitivity, measured by high-pass resolution (HRP) visual fields, in children
      surgically treated for congenital cataract. METHODS: Acuity and peripheral
      sensitivity were recorded from 16 children, aged 10 to 15 years, either
      surgically treated for bilateral dense cataract before the age of 4.6 months (n =
      10) or surgically treated for bilateral partial cataract at ages 4 to 139 months
      (n = 6). Data from 22 healthy children, mean age 11 years, served as control.
      RESULTS: The children with cataract had significantly (P < 0.0001) lower decimal
      acuity in their better eye (median, 0.55; range, 0.1-1.3) than did the control
      subjects (median, 1.2; range, 1.0-1.6). Five children were visually impaired
      according to the World Health Organization's definition (i.e., acuity in the
      better eye <0.3). The children with previous dense bilateral cataract showed
      significantly lower peripheral sensitivity than did the control subjects (P =
      0.004). Significant correlations were observed between acuity and visual field
      parameters. CONCLUSIONS: Dense cataract, even when surgically treated before the
      age of 4.6 months, causes persistent impairment of spatial vision, both in the
      fovea and the visual field. The effect on the visual field is less pronounced
      than that on visual acuity. This finding has to be taken into account when
      evaluating visual field results in, for example, the diagnosis of glaucoma, a
      frequent complication after cataract surgery in early infancy.

PMID- 18344448
TI  - Effects of bevacizumab (Avastin) on retinal cells in organotypic culture.
AB  - PURPOSE: Repetitive intravitreal injections of bevacizumab are a successful
      treatment option for exudative age-related macular degeneration (AMD). The aim of
      this study was to evaluate the toxicity of bevacizumab in the adult mammalian
      neurosensory retina in culture. METHODS: Adult porcine neurosensory retinas were
      cultured adjoined to the retinal pigment epithelium-choroid layer (retina-RPE
      choroid complex) in static culture for 3 days, whereas neural retinas alone were
      cultured in a perfusion chamber for 3 days. Bevacizumab was added to the culture
      and perfusion medium at three concentrations (0.25 mg/mL [n = 6], 0.5 mg/mL [n =
      6], and 1.25 mg/mL [n = 6]). Retina-RPE-choroid complex and neural retinas alone
      cultured without bevacizumab were used as controls. After 3 days in culture, the
      neural retinas alone and the retina-RPE-choroid complexes were analyzed
      histologically and immunohistochemically for the expression of glial fibrillary
      acidic protein (GFAP), vimentin, glutamine synthetase, rhodopsin, smooth muscle
      actin (SMA), and apoptosis. RESULTS: No toxic effects on ganglion or
      photoreceptor cells were observed at any concentration of bevacizumab. The
      expression of GFAP and vimentin was slightly increased in Muller cells, whereas
      glutamine synthetase and rhodopsin were unaffected by bevacizumab. However,
      significantly enhanced SMA expression in retina blood vessels was observed in
      retinas cultured in the presence of bevacizumab. CONCLUSIONS: Bevacizumab was
      well tolerated by ganglion and photoreceptor cells even at concentrations
      fivefold higher than those used clinically. The increased expression of SMA is an
      indication of the loss of functional VEGF modulating smooth muscle cells in
      mature vessels.

PMID- 18344449
TI  - Influence of a quantitative trait locus on mouse chromosome 19 to the light
      adapted electroretinogram.
AB  - PURPOSE: Both implicit time and amplitude of the cone-mediated
      electroretinographic (ERG) b-wave differ significantly between the C57BL/6JOlaHsd
      and 129S2/SvHsd inbred mouse strains. The purpose of this work was to undertake a
      quantitative genetics study to localize the gene or genes involved. METHODS:
      Implicit time and amplitude of the a- and b-waves of the single-flash and flicker
      cone-mediated ERG were recorded as the quantitative traits in reciprocal
      backcrossed populations. A genome-wide scan was performed with 106 polymorphic
      markers. Map Manager (release QTXb20) was used to analyze the data and make
      phenotype-genotype correlations. RESULTS: A quantitative trait locus (QTL) of
      major effect in controlling variation in both implicit time and amplitude of the
      cone-mediated ERG localized to the middle of chromosome 19. CONCLUSIONS: Mapping
      of a QTL influencing both implicit time and b-wave amplitude of the light-adapted
      ERG represents an initial step toward identifying the gene(s) responsible for
      this phenotypic variation.

PMID- 18344450
TI  - Retinal pathology in a canine model of late infantile neuronal ceroid
      lipofuscinosis.
AB  - PURPOSE: Late infantile neuronal ceroid lipofuscinosis (NCL) is an inherited
      disorder characterized by progressive vision loss. The disease results from
      mutations in the TPP1 (CLN2) gene. Studies were undertaken to characterize the
      effects of a TPP1 frameshift mutation on the retina in Dachshunds. METHODS: A
      litter of four puppies consisting of one homozygous affected dog, two
      heterozygotes, and one homozygous normal dog were monitored for neurologic and
      retinal changes through 10 months of age. The affected and homozygous normal
      dogs, as well as one of the heterozygotes, were then euthanatized, and the
      retinas were examined morphologically. RESULTS: The affected dog exhibited normal
      visual behavior and retinal function at 3 months of age, but vision was clearly
      impaired by 7 months, with markedly reduced ERG b-wave amplitudes. Beyond 7
      months of age, the affected dog was functionally blind, and pupillary light
      reflexes and ERG response amplitudes continued to decline through 10 months of
      age. Both rod and cone system functions were severely impaired. The retina
      exhibited accumulation of autofluorescent storage bodies with distinctive
      curvilinear contents. Substantial cell loss occurred in the inner nuclear layer,
      with a smaller reduction in photoreceptor cell density. CONCLUSIONS: The canine
      TPP1 mutation results in progressive vision loss and retinal degeneration similar
      to that which occurs in human late infantile NCL. With the canine model, the
      natural history of disease progression in the retina provides a better
      understanding of the pathologic course of the disease and provides objective
      markers that can be used to assess the efficacy of therapeutic interventions.

PMID- 18344452
TI  - Secretoglobins: lacrimal gland-specific rabbit lipophilin mRNAs.
AB  - PURPOSE: RNAs encoding secretoglobin subunits, also known as lipophilins, are
      found in rabbit lacrimal glands. Some secretoglobins in other species are tissue-
      and/or sex-specific, whereas other secretoglobins are expressed in a variety of
      tissues of both sexes. In this study the tissue-specific and sexual dimorphic
      expression patterns of rabbit lacrimal gland lipophilins AL, AL2, BL, CL, and CL2
      were determined. METHODS: RNAs from male and female rabbit lacrimal glands were
      compared in a differential display analysis, and a new rabbit lacrimal gland
      secretoglobin, lipophilin AL2, was identified. Next, RNAs from male and female
      rabbit harderian, lacrimal, mandibular, sublingual, and parotid glands and from
      liver, kidney, pancreas, testis (male), ovary, and mammary gland (female) were
      isolated, electrophoresed in agarose gels, and transferred to nylon membranes.
      cDNA probes encoding the lipophilins AL, AL2, BL, and CL/CL2 were hybridized to
      the RNA in the blots. RESULTS: Rabbit mRNAs encoding the lipophilins AL, AL2, BL,
      CL, and CL2 were detected only in the lacrimal gland. Lipophilin AL2 mRNA was
      detected only in male rabbit lacrimal gland. CONCLUSIONS: In the rabbit, several
      lipophilins were expressed only in the lacrimal gland.

PMID- 18344451
TI  - Mitochondrial proteomics of the retinal pigment epithelium at progressive stages
      of age-related macular degeneration.
AB  - PURPOSE: Age-related macular degeneration (AMD) is the leading cause of vision
      loss in individuals over the age of 65. Histopathological changes become evident
      in the retinal pigment epithelium (RPE), a monolayer that provides metabolic
      support for the overlying photoreceptors, even at the earliest stages of AMD that
      precede vision loss. In a previous global RPE proteome analysis, changes were
      identified in the content of several mitochondrial proteins associated with AMD.
      In this study, the subproteome of mitochondria isolated from human donor RPE
      graded with the Minnesota Grading System (MGS) was analyzed. METHODS: Human donor
      eye bank eyes were categorized into one of four progressive stages (MGS 1-4)
      based on the clinical features of AMD. After dissection of the RPE, mitochondrial
      proteins were isolated and separated by two-dimensional gel electrophoresis based
      on their charge and mass. Protein spot densities were compared between the four
      MGS stages. Peptides from spots that changed significantly with MGS stage were
      extracted and analyzed by using mass spectrometry to identify the protein.
      RESULTS: Western blot analyses verified that mitochondria were consistently
      enriched between MGS stages. The densities of eight spots increased or decreased
      significantly as a function of MGS stage. These spots were identified as the
      alpha-, beta-, and delta-ATP synthase subunits, subunit VIb of the cytochrome c
      oxidase complex, mitofilin, mtHsp70, and the mitochondrial translation factor Tu.
      CONCLUSIONS: The results are consistent with the hypothesis that mitochondrial
      dysfunction is associated with AMD and further suggest specific
      pathophysiological mechanisms involving altered mitochondrial translation, import
      of nuclear-encoded proteins, and ATP synthase activity.

PMID- 18344453
TI  - Coping with a child with Dravet syndrome: insights from families.
AB  - Dravet syndrome is a truly catastrophic childhood-onset epilepsy. Families are
      faced with repeated episodes of status epilepticus, intractable seizures, mental
      handicap, behavior disorders, and a life of dependency; understandably, coping
      with Dravet syndrome is very difficult. Twenty-four families with a child with
      Dravet syndrome were interviewed and identified some practical suggestions to
      improve their daily life. These included inserting an indwelling venous access
      device, creating a portable microenvironment, writing an emergency department
      protocol, establishing emergency routines for the family, assigning a parent on
      call to lessen the effect on siblings, creating personal time to decrease
      parental stress, finding respite care, and contacting an Internet support group.
      Unresolved and common issues included transition to adult care, the utility of
      early diagnosis, and social isolation. These solutions and issues may be helpful
      to many families with a child with Dravet syndrome and possibly other severe
      childhood-onset epilepsies.

PMID- 18344454
TI  - Use of surface electromyography (EMG) in the diagnosis of childhood hypertonia: a
      pilot study.
AB  - In children, increased tone in a joint can be caused by spasticity, dystonia,
      rigidity, or mechanical limitations such as contracture. Determination of the
      cause of hypertonia is important for selection of appropriate therapy, but
      distinction between the types of hypertonia is difficult in a clinical setting.
      We present results of a pilot test of the use of a portable surface
      electromyography (EMG) device for the evaluation of hypertonia. Seven children 5
      17 years of age with hypertonia due to cerebral palsy were each examined by 6
      clinicians, both with and without the use of surface EMG. The use of surface EMG
      resulted in an increase in interrater agreement as well as an increase in the
      self-reported confidence of the clinicians in their assessment. These results
      support the importance of further testing of surface EMG as an adjunct to the
      clinical examination of childhood hypertonia.

PMID- 18344455
TI  - Simultaneous toxicities in a child on multiple anticonvulsants.
AB  - It is rare to develop simultaneous toxicities while on anticonvulsants. This
      article presents a 3(1/2)-year-old child on valproic acid, lamotrigine, and
      phenytoin who developed simultaneous hepatotoxicity and bone marrow toxicity
      during a parainfluenza virus type 3 infection. These toxicities resolved after
      the cessation of anticonvulsants, and her seizures were managed acutely with
      scheduled lorazepam. This article discusses the possibility that simultaneous use
      of valproic acid, lamotrigine, and phenytoin could give this combination of
      toxicities and that concurrent viral infection may increase this risk.

PMID- 18344456
TI  - Association of the dusp6 (mkp3) gene with mouse brain weight and forebrain
      structure.
AB  - PYST1/MKP3 is a negative feedback modulator of fibroblast growth factor 8 (Fgf8)
      signaling in the mammalian isthmic organizer of the brain, which affects the
      development of the midbrain and the hindbrain. The Dusp6 (Mkp3) gene is also
      highly expressed in the mouse embryonic forebrain. However, its role in forebrain
      development and function remains largely unknown. In this study, association
      analyses were preformed in silico between the variation I62M (rs13480726) of the
      Dusp6 (Mkp3) gene and the mouse forebrain weight/structure in 385 mice of 20
      strains. It was found that I62M (allele A) was associated with reduced mouse
      forebrain structure in both sexes and lower brain weight in males.

PMID- 18344457
TI  - Neurologic findings in infants with deformational plagiocephaly.
AB  - This study evaluates the neurologic profiles of infants with deformational
      plagiocephaly. Forty-nine infants with deformational plagiocephaly between the
      ages of 4 and 13 months (mean age, 8.1 months) are evaluated, along with 50 age
      matched control subjects (mean age, 8.1 months). A modified version of the
      Hammersmith infant neurologic assessment was performed on each infant. A
      caregiver completed a questionnaire regarding the infant's prematurity,
      development, and health to date. Results are analyzed using t test. There is a
      statistically significant difference in overall neurologic assessment scores of
      infants with deformational plagiocephaly vs their healthy peers (P = .002). This
      difference is predominately in tone, whereby infants with deformational
      plagiocephaly have significantly more abnormal tone than nonplagiocephalic
      infants (P = .003). This abnormality is not one of decreased tone but one of
      variable tone, deflecting abnormally high and low tone. Infants with
      deformational plagiocephaly are more likely to have altered tone but not
      exclusively decreased tone.

PMID- 18344458
TI  - Spinocerebellar ataxia type 2 presenting with cognitive regression in childhood.
AB  - Spinocerebellar ataxia type 2 typically presents in adulthood with progressive
      ataxia, dysarthria, tremor, and slow saccadic eye movements. Childhood-onset
      spinocerebellar ataxia type 2 is rare, and only the infantile-onset form has been
      well characterized clinically. This article describes a girl who met all
      developmental milestones until age 3(1/2) years, when she experienced cognitive
      regression that preceded motor regression by 6 months. A diagnosis of
      spinocerebellar ataxia type 2 was delayed until she presented to the emergency
      department at age 7 years. This report documents the results of her
      neuropsychologic evaluation at both time points. This case broadens the spectrum
      of spinocerebellar ataxia type 2 presentation in childhood, highlights the
      importance of considering a spinocerebellar ataxia in a child who presents with
      cognitive regression only, and extends currently available clinical information
      to help clinicians discuss the prognosis in childhood spinocerebellar ataxia type
      2.

PMID- 18344459
TI  - A case of pediatric tumefactive demyelinating lesion misdiagnosed and treated as
      glioblastoma.
AB  - Because of their clinical and neuroradiological features, tumefactive
      demyelinating lesions, or giant plaques, are easily mistaken for tumors, with a
      consequent risk of gross errors in the choice of treatment. This article reports
      a 10-year-old girl who underwent surgery for a left parietal lesion
      misinterpreted as a glioblastoma which subsequently proved to be a case of giant
      plaque.

PMID- 18344460
TI  - Doctors: the media's favourite worst nightmare.

PMID- 18344461
TI  - Tuberculosis--the tide can be turned, the battle can be won.

PMID- 18344462
TI  - Involving medical students in research.

PMID- 18344463
TI  - William Bateson, the rediscoverer of Mendel.

PMID- 18344464
TI  - The cardiovascular morbidity associated with hyperglycaemia.

PMID- 18344465
TI  - Strategic challenges in the prevention of cardiovascular disease.

PMID- 18344466
TI  - The dignity and privacy of patients.

PMID- 18344467
TI  - Beverly Allitt: the nurse who killed babies.

PMID- 18344468
TI  - Recent advances in hearing restoration.
AB  - This review is based on Pubmed, Medline and Internet literature searches,
      supplemented by knowledge from textbooks, conference presentations, and personal
      communications with experts in the field of hearing restoration and patients. We
      have not specifically selected a time limit for our literature searches; however,
      the majority are articles from the past 5 years.

PMID- 18344469
TI  - Deconstructing media coverage of trastuzumab (Herceptin): an analysis of national
      newspaper coverage.
AB  - OBJECTIVE: To explore and critically describe the content and main narratives of
      UK national daily newspaper coverage of trastuzumab (Herceptin). DESIGN: We used
      the NewsBank database to search eight national daily newspapers, and their Sunday
      equivalents, retrospectively from 19 February 2006 back to the earliest mention
      of trastuzumab or Herceptin (19 May 1998). Setting UK national newspapers. MAIN
      OUTCOME MEASURES: To be eligible for inclusion, articles had to contain at least
      three sentences about trastuzumab. Articles that focused on the financial
      performance of companies associated with the drug were excluded from the
      analysis. For each included article, we extracted bibliographic details and data,
      and independently rated the reporting slant towards trastuzumab and, where
      relevant, the reporting slant towards access to treatment. RESULTS: We identified
      361 articles that met the study inclusion criteria. The proprietary name of
      Herceptin was always used, with only eight articles mentioning the generic
      alternative. 294/361 included articles (81.5%) were rated as being positive
      towards trastuzumab, the remainder rated as neutral. Access to trastuzumab
      treatment was the main narrative running across included articles and reports of
      individual patients seeking treatment featured prominently throughout. In 208/361
      of included articles (57%) the reporting slant towards access to trastuzumab
      treatment was rated as negative. 178/361 of included articles (49.3%) mentioned
      licensing, but rarely mentioned that licensing processes can only occur when the
      manufacturer applies for a licence. Only a minority of articles mentioned that
      the drug had to be licensed before it could be subject to the NICE approval
      process. CONCLUSIONS: Newspaper coverage of trastuzumab has been characterized by
      uncritical reporting. Journalists (and consumers) should be more questioning when
      confronted with information about new drugs and of the motives of those who seek
      to set the news agenda.

PMID- 18344470
TI  - Proxy assessment of quality of life in patients with prostate cancer: how
      accurate are partners and urologists?
AB  - OBJECTIVES: To assess the ability of partners and clinicians to make proxy
      judgements on behalf of patients with prostate cancer relating to selection of
      life priorities and quality of life (QoL). DESIGN: 47 consecutive patients with
      histologically proven adenocarcinoma, and their partners, were recruited. The
      partners were asked to assess, by proxy, the QoL of the patient by completion of
      a series of interview-led questionnaires assessing global QoL (SEIQoL-DW), health
      related QoL (FACT-P) and overall QoL (visual analogue score [VAS]). The patients'
      clinicians were asked to complete the SEIQoL-DW and VAS by proxy as soon as
      possible after a consultation with the patient. SETTING: Patients with
      histologically proven adenocarcinoma, their partners and their clinicians. MAIN
      OUTCOME MEASURES: Proxy scores for SEIQoL-DW, FACT-P and VAS, as provided by
      partners and clinicians. RESULTS: 25 partners made a proxy assessment of the
      patients. The results showed that partners were able to select similar QoL cues
      to those of the patients (Spearman-Rank correlation 0.89). Comparison of the QoL
      scores obtained from patients and partners in proxy using the questionnaires
      showed no statistically significant difference (paired t-test). Urologists were
      poor predictors of areas of life (cues) that were important to their patients.
      The doctors overemphasized the importance of survival, postoperative
      complications, urinary symptoms, sexual ability, activities of daily living and
      finance, but underestimated the importance of wife, family, home and religion.
      Comparison of the QoL scores obtained from patients and urologists by proxy
      showed a significantly lower score when assessed by urologists using the SEIQoL
      DW questionnaire. CONCLUSIONS: Partners are able to accurately assess, by proxy,
      the areas of life that are of importance to patients. Clinicians, however, who
      are charged with making decisions on behalf of patients, are very poor judges of
      their patients' life priorities and QoL. This illustrates that conventional views
      held by most doctors regarding the priorities patients set themselves when
      planning treatment should be called into question and consequently suggests that
      the way in which doctors and patients arrive at treatment decisions must be
      reviewed.

PMID- 18344471
TI  - Trends in national incidence, lifetime prevalence and adrenaline prescribing for
      anaphylaxis in England.
AB  - BACKGROUND: Analysis of primary healthcare datasets offers the possibility to
      increase understanding of the epidemiology of acute uncommon conditions such as
      anaphylaxis, but these datasets remain under-exploited. AIM: To investigate
      recent trends in the recorded incidence, lifetime prevalence and prescribing of
      adrenaline for anaphylaxis in England. METHODS: QRESEARCH is one of the world's
      largest national aggregated health databases containing the records of over nine
      million patients. We extracted data on all patients with a recorded diagnosis of
      anaphylaxis and calculated annual age-sex standardized incidence and lifetime
      period prevalence rates for each year from 2001-2005. We also analysed trends in
      adrenaline prescribing in those with a recorded diagnosis of anaphylaxis.
      National population figures were used to estimate numbers of people in England
      that have experienced anaphylaxis at some point in their lives. RESULTS: The age
      sex standardized incidence of anaphylaxis was 6.7 per 100,000 person-years in
      2001 and increased by 19% to 7.9 in 2005. Lifetime age-sex standardized
      prevalence of a recorded diagnosis of anaphylaxis was 50.0 per 100,000 in 2001
      and increased by 51% to 75.5 in 2005. Prescribing of adrenaline increased by 97%
      over this period. By the end of 2005 there were an estimated 37,800 people that
      had experienced anaphylaxis at some point in their lives. CONCLUSIONS: Recorded
      incidence, lifetime prevalence and prescribing of adrenaline for anaphylaxis all
      showed substantial increases in recent years. An estimated 1 in 1,333 of the
      English population have at some point in their lives experienced anaphylaxis.

PMID- 18344472
TI  - Dysphagia with a thyroid nodule: is there a primary aerodigestive malignancy?
AB  - Three cases of laryngopharyngeal primary squamous cell carcinoma presenting with
      thyroid nodules are described. The key message to take away from these cases is
      that patients with advanced malignancy of the upper aerodigestive tract can
      present with a thyroid nodule.

PMID- 18344473
TI  - The use of historical controls and concurrent controls to assess the effects of
      sulphonamides, 1936-1945.

PMID- 18344474
TI  - The big idea: polonium, radon and cigarettes.

PMID- 18344475
TI  - Jumping in a wingless stick insect, Timema chumash (Phasmatodea, Timematodea,
      Timematidae).
AB  - The stick insect Timema chumash belongs to a sub-order of the phasmids that is
      thought to have diverged early from other stick insects, and which is restricted
      to the southwest of North America. It jumps by rapidly extending the tibiae of
      both its hind legs simultaneously from an initially fully flexed position, unlike
      any other stick insect that has been described. The hind legs are 1.5 times
      longer than the front and middle legs, but still represent only half the length
      of its body, and the femoro-tibial joints show few specialisations for jumping.
      In its best jumps, the wingless body is accelerated in 12 ms to a take-off
      velocity of 0.9 m s(-1) and experiences an acceleration of 75 m s(-2), the
      equivalent of 8 g. This performance requires an energy expenditure of 19 microJ,
      generates a power output of 1.6 mW and exerts a force of 3.6 mN. The jump propels
      the body forward a distance of 80 mm from a mean take-off angle of 39 degrees .
      Heights of 20 mm were also achieved. Elevation of the jump was controlled by the
      initial position of the hind legs; when the hind tibiae and femora projected
      above the dorsal outline of the body the jump was forwards, when parallel with
      the long axis of the body the jump was backwards and could result in
      somersaulting. The jumping movements would appear to displace Timema in different
      directions away from a potential predator.

PMID- 18344476
TI  - The correlated evolution of biomechanics, gait and foraging mode in lizards.
AB  - Foraging mode has molded the evolution of many aspects of lizard biology. From a
      basic sit-and-wait sprinting feeding strategy, several lizard groups have evolved
      a wide foraging strategy, slowly moving through the environment using their
      highly developed chemosensory systems to locate prey. We studied locomotor
      performance, whole-body mechanics and gaits in a phylogenetic array of lizards
      that use sit-and-wait and wide-foraging strategies to contrast the functional
      differences associated with the need for speed vs slow continuous movement during
      foraging. Using multivariate and phylogenetic comparative analyses we tested for
      patterns of covariation in gaits and locomotor mechanics in relation to foraging
      mode. Sit-and-wait species used only fast speeds and trotting gaits coupled with
      running (bouncing) mechanics. Different wide-foraging species independently
      evolved slower locomotion with walking (vaulting) mechanics coupled with several
      different walking gaits, some of which have evolved several times. Most wide
      foragers retain the running mechanics with trotting gaits observed in sit-and
      wait lizards, but some wide foragers have evolved very slow (high duty factor)
      running mechanics. In addition, three evolutionary reversals back to sit-and-wait
      foraging are coupled with the loss of walking mechanics. These findings provide
      strong evidence that foraging mode drives the evolution of biomechanics and gaits
      in lizards and that there are several ways to evolve slower locomotion. In
      addition, the different gaits used to walk slowly appear to match the ecological
      and behavioral challenges of the species that use them. Trotting appears to be a
      functionally stable strategy in lizards not necessarily related to whole-body
      mechanics or speed.

PMID- 18344477
TI  - Persistence of motor unit and muscle fiber types in the presence of inactivity.
AB  - The clarity of categorizing skeletal muscle fibers in individual motor units into
      phenotypes based on quantitative single fiber enzyme activities and as a function
      of neuromuscular activity level was examined. Neuromuscular activity was
      eliminated in adult cat hindlimb muscles by spinal cord isolation (SI), i.e.
      complete spinal cord transection at a low thoracic and a high sacral level with
      bilateral dorsal rhizotomy between the transection sites. One motor unit was
      isolated via ventral root teasing procedures from the tibialis anterior (TA)
      muscle of each hindlimb in control and SI cats, and physiologically tested and
      glycogen depleted through repetitive stimulation; fibers comprising each motor
      unit were visualized through glycogen staining. Each motor unit was composed of
      fibers of the same myosin immunohistochemical type. Myofibrillar adenosine
      triphosphatase, succinate dehydrogenase and alpha-glycerophosphate dehydrogenase
      activities were determined for a sample of motor unit and non-motor unit fibers,
      providing a measure of three enzyme activities often used to characterize fiber
      phenotype within a single unit. Although normal enzyme activities were altered
      after 6 months of inactivity, the relationships among the three enzymes were
      largely maintained. These data demonstrate that it is not the diversity in any
      single enzyme property but the profile of several metabolic pathways that
      underlies the significance of fiber phenotypes. These profiles must reflect a
      high level of coordination of expression of selected combinations of genes.
      Although neuromuscular activity level influences fiber phenotype, the present
      results demonstrate that activity-independent mechanisms remain important sources
      of the control of phenotype establishment in the near absence of activity.

PMID- 18344478
TI  - The effect of thermal history on the susceptibility of reef-building corals to
      thermal stress.
AB  - The mutualistic relationship between corals and their unicellular dinoflagellate
      symbionts (Symbiodinium sp.) is a fundamental component within the ecology of
      coral reefs. Thermal stress causes the breakdown of the relationship between
      corals and their symbionts (bleaching). As with other organisms, this symbiosis
      may acclimate to changes in the environment, thereby potentially modifying the
      environmental threshold at which they bleach. While a few studies have examined
      the acclimation capacity of reef-building corals, our understanding of the
      underlying mechanism is still in its infancy. The present study focused on the
      role of recent thermal history in influencing the response of both corals and
      symbionts to thermal stress, using the reef-building coral Acropora aspera. The
      symbionts of corals that were exposed to 31 degrees C for 48 h (pre-stress
      treatment) 1 or 2 weeks prior to a 6-day simulated bleaching event (when corals
      were exposed to 34 degrees C) were found to have more effective photoprotective
      mechanisms. These mechanisms included changes in non-photochemical quenching and
      xanthophyll cycling. These differences in photoprotection were correlated with
      decreased loss of symbionts, with those corals that were not prestressed
      performing significantly worse, losing over 40% of their symbionts and having a
      greater reduction in photosynthetic efficiency. These results are important in
      that they show that thermal history, in addition to light history, can influence
      the response of reef-building corals to thermal stress and therefore have
      implications for the modeling of bleaching events. However, whether acclimation
      is capable of modifying the thermal threshold of corals sufficiently to cope as
      sea temperatures increase in response to global warming has not been fully
      explored. Clearly increases in sea temperatures that extend beyond 1-2 degrees C
      will exhaust the extent to which acclimation can modify the thermal threshold of
      corals.

PMID- 18344479
TI  - Thermodynamics of oxygenation-linked proton and lactate binding govern the
      temperature sensitivity of O2 binding in crustacean (Carcinus maenas) hemocyanin.
AB  - With the aim of understanding the molecular underpinnings of the enormous
      variation in the temperature sensitivity of hemocyanin-O2 affinity encountered in
      crustaceans, we measured O2 binding to Carcinus maenas hemocyanin at two
      temperatures, varying pH values and in the absence and presence of lactate ions
      in order to assess the contributions of oxygenation-linked binding of protons
      (the Bohr effect) and lactate ions to the overall enthalpies of oxygenation
      (DeltaH'). The hemocyanin binds maximally 0.35 lactate ions per functional
      subunit. Lactate (which accumulates under hypoxic conditions) increases O2
      affinity by preferentially raising the association equilibrium constant of the
      hemocyanin in the low-affinity Tense state (KT), without significantly affecting
      that of the high-affinity Relaxed state (KR). In the absence of lactate, the
      variation in the temperature sensitivity observed with decreasing pH tallies
      neatly with changes in the nature and magnitude of the Bohr effect. Accordingly,
      the normal, absent and reverse Bohr effects observed under alkaline, neutral and
      acid conditions, respectively, reflect endothermic proton dissociation, absence
      of proton binding and exothermic proton association, respectively, upon oxygen
      binding. Oxygenation-linked lactate binding is exothermic, highly pH dependent
      and peaks near pH 7.6, where it contributes approximately -30 kJ mol(-1) to the
      overall heat of oxygenation. This predictably increases the temperature
      sensitivity of O2 affinity, potentially hampering O2 loading in warm, hypoxic
      habitats. The data demonstrate governing roles for lactate and proton ions in
      determining the temperature sensitivity of hemocyanin-O2 affinity in crustaceans.

PMID- 18344480
TI  - The effect of hypoxia on gill morphology and ionoregulatory status in the Lake
      Qinghai scaleless carp, Gymnocypris przewalskii.
AB  - Goldfish and crucian carp at low temperature exhibit plasticity in gill
      morphology during exposure to hypoxia to enhance gas exchange. Hypoxia-induced
      changes in gill morphology and cellular ultrastructure of the high altitude
      scaleless carp from Lake Qinghai, China, were investigated to determine whether
      this is a general characteristic of cold water carp species. Fish were exposed to
      acute hypoxia (0.3 mg O2 l(-1)) for 24 h followed by 12 h recovery in normoxic
      water (6 mg O2 l(-1) at 3200 m altitude), with no mortality. Dramatic alterations
      in gill structure were initiated within 8 h of hypoxia and almost complete by 24
      h, and included a gradual reduction of filament epithelial thickness (>50%),
      elongation of respiratory lamellae, expansion of lamellar respiratory surface
      area (>60%) and reduction in epithelial water-blood diffusion distance (<50%). An
      increase in caspase 3 activity in gills occurred following 24 h exposure to
      hypoxia, indicating possible involvement of apoptosis in gill remodeling.
      Extensive gill mucous production during hypoxia may have been part of a general
      stress response or may have played a role in ion exchange and water balance. The
      large increase in lamellar surface area and reduction in diffusion distance
      presumably enhances gas transfer during hypoxia (especially in the presence of
      increased mucous production) but comes with an ionoregulatory cost, as indicated
      by a 10 and 15% reduction in plasma [Na+] and [Cl-], respectively, within 12-24 h
      of hypoxia. Within 12 h of hypoxia exposure, ;wavy-convex'-mitochondria rich
      cells (MRCs) with large apical crypts and numerous branched microvilli were
      transformed into small ;shallow-basin' cells with a flattened surface. As the
      apical membrane of MRCs is the site for active ion uptake from the water, a
      reduction in apical crypt surface area may have contributed to the progressive
      reduction in plasma [Na+] and [Cl-] observed during hypoxia. The changes in the
      macro- and ultra-structure of fish gills, and plasma [Na+] and [Cl-] during
      hypoxia were reversible, showing partial recovery by 12 h following return to
      normoxia. Although the large morphological changes in the gill observed in the
      scaleless carp support the hypothesis that gill remodeling during hypoxia is a
      general characteristic of cold water carp species, the reduced magnitude of the
      response in scaleless carp relative to goldfish and crucian carp may be a
      reflection of their more active lifestyle or because they reside in a moderately
      hypoxic environment at altitude.

PMID- 18344481
TI  - Involvement of lactate in glucose metabolism and glucosensing function in
      selected tissues of rainbow trout.
AB  - The aim of this study was to obtain evidence in rainbow trout for a role of
      lactate in glucose homeostasis as well as in the function of glucosensing
      tissues. In a first set of experiments, trout were injected, either (1)
      intraperitoneally (N=8) with 5 ml kg(-1) of Cortland saline alone (control) or
      saline containing l-(+)-lactate (22.5 mg kg(-1) or 45 mg kg(-1)), oxamate (22.5
      mg kg(-1)) or d-glucose (500 mg kg(-1)), or (2) intracerebroventricularly (N=11)
      with 1 microl 100 g(-1) body mass of Cortland saline alone (control) or
      containing d-glucose (400 microg microl(-1)) or l-(+)-lactate (400 microg microl(
      1)), with samples being obtained 6 h after treatment. In a second set of
      experiments, hypothalamus, hindbrain and Brockmann bodies were incubated in vitro
      for 1 h at 15 degrees C in modified Hanks' medium containing 2, 4 or 8 mmol l(-1)
      l-(+)-lactate alone (control) or with 50 mmol l(-1) oxamate, 1 mmol l(-1) DIDS, 1
      mmol l(-1) dichloroacetate, 10 mmol l(-1) 2-deoxy-d-glucose, 1 mmol l(-1) alpha
      cyano-4-hydroxy cinnamate or 10 mmol l(-1) d-glucose. The response of parameters
      assessed (metabolite levels, enzyme activities and glucokinase expression) in
      tissues provided evidence for (1) a role for lactate in the regulation of glucose
      homeostasis through changes not only in brain regions but also in liver energy
      metabolism, which are further reflected in changes in plasma levels of
      metabolites; (2) the possible presence in trout brain of an astrocyte-neuron
      lactate shuttle similar to that found in mammals; and (3) the lack of capacity of
      lactate to mimic in vitro (but not in vivo) glucose effects in fish glucosensing
      regions.

PMID- 18344482
TI  - The effect of increasing inertia upon vertical ground reaction forces and
      temporal kinematics during locomotion.
AB  - The addition of inertia to exercising astronauts could increase ground reaction
      forces and potentially provide a greater health benefit. However, conflicting
      results have been reported regarding the adaptations to additional mass (inertia)
      without additional net weight (gravitational force) during locomotion. We
      examined the effect of increasing inertia while maintaining net gravitational
      force on vertical ground reaction forces and temporal kinematics during walking
      and running. Vertical ground reaction force was measured for 10 healthy adults
      (five male/five female) during walking (1.34 m s(-1)) and running (3.13 m s(-1))
      using a force-measuring treadmill. Subjects completed locomotion at normal weight
      and mass and at 10, 20, 30 and 40% of added inertial force. The added
      gravitational force was relieved with overhead suspension, so that the net force
      between the subject and treadmill at rest remained equal to 100% body weight.
      Ground reaction forces were affected by the added inertial force, but not to the
      magnitude predicted by the increase in mass, suggesting that adaptations in
      motion occurred. Vertical ground reaction force production and adaptations in
      gait temporal kinematics were different between walking and running. Peak
      vertical impact forces and loading rates increased with increased inertia during
      walking, and decreased during running. As inertia increased, peak vertical
      propulsive forces decreased during walking and did not change during running.
      Stride time increased during walking and running, and contact time increased
      during running. The increased inertial forces were utilized independently from
      gravitational forces by the motor control system when determining coordination
      strategies.

PMID- 18344483
TI  - The effect of food temperature on postprandial metabolism in albatrosses.
AB  - Heat generated by the specific dynamic action (SDA) associated with feeding is
      known to substitute for the thermoregulatory costs of cold-exposed endotherms;
      however, the effectiveness of this depends on food temperature. When food is
      cooler than core body temperature, it is warmed by body heat and, consequently,
      imposes a thermoregulatory challenge to the animal. The degree to which this cost
      might be ;paid' by SDA depends on the relative timing of food heating and the SDA
      response. We investigated this phenomenon in two genera of endotherms, Diomedea
      and Thalassarche albatrosses, by measuring postprandial metabolic rate following
      ingestion of food at body temperature (40 degrees C) and cooler (0 and 20 degrees
      C). This permitted us to estimate potential contributions to food warming by SDA
      derived heat, and to observe the effect of cold food on metabolic rate. For meal
      sizes that were approximately 20% of body mass, SDA was 4.22+/-0.37% of
      assimilated food energy, and potentially contributed 17.9+/-1.0% and 13.2+/-2.2%
      of the required heating energy of food at 0 degrees C for Diomedea and
      Thalassarche albatrosses, respectively, and proportionately greater quantities at
      higher food temperatures. Cold food increased the rate at which postprandial
      metabolic rate increased to 3.2-4.5 times that associated with food ingested at
      body temperature. We also found that albatrosses generated heat in excess by more
      than 50% of the estimated thermostatic heating demand of cold food, a probable
      consequence of time delays in physiological responses to afferent signals.

PMID- 18344484
TI  - Biochemical and functional characterization of the actin-binding activity of the
      B subunit of yeast vacuolar H+-ATPase.
AB  - Vacuolar H+-ATPase (V-ATPase) is a fundamentally important enzyme in eukaryotic
      cells that is responsible for acidification of endocytic compartments. The B
      subunits of V-ATPases from mammals and tobacco hornworm have been shown to bind
      actin filaments. Actin-binding activity by the B subunit is required for
      targeting V-ATPases to the plasma membrane of osteoclasts. Bacterially expressed
      B subunit from the yeast Saccharomyces cerevisiae bound actin filaments with a Kd
      of 195 nmol l(-1). The actin-binding domain of the B subunit was altered by
      mutations that reduced or eliminated the actin-binding activity. Mutants
      assembled properly with endogenous yeast subunits when expressed in B subunit
      null yeast and bafilomycin-sensitive ATPase activity was not significantly
      different from yeast transformed with wild-type B subunit. Yeast containing the
      mutant subunits grew as well at pH 7.5 as wild-type. Screening null yeast or null
      yeast transformed with wild-type or mutant B subunits with sub-lethal doses of
      various drugs revealed that yeast containing the mutant B subunits were more
      sensitive to cycloheximide and wortmannin than those transformed with wild-type B
      subunits. These results suggest that actin-binding activity confers on the B
      subunit of yeast a function that is distinct from its role in the enzymatic
      activity of the proton pump.

PMID- 18344485
TI  - The mandible opening response: quantifying aggression elicited by chemical cues
      in ants.
AB  - Social insects have evolved efficient recognition systems guaranteeing social
      cohesion and protection from enemies. To defend their territories and threaten
      non-nestmate intruders, ants open their mandibles as a first aggressive display.
      Albeit chemical cues play a major role in discrimination between nestmates and
      non-nestmates, classical bioassays based on aggressive behaviour were not
      particularly effective in disentangling chemical perception and behavioural
      components of nestmate recognition by means of categorical variables. We
      therefore developed a novel bioassay that accurately isolates chemical perception
      from other cues. We studied four ant species: Camponotus herculeanus, C. vagus,
      Formica rufibarbis and F. cunicularia. Chemical analyses of cuticular extracts of
      workers of these four species showed that they varied in the number and identity
      of compounds and that species of the same genus have more similar profiles. The
      antennae of harnessed ants were touched with a glass rod coated with the
      cuticular extract of (a) nestmates, (b) non-nestmates of the same species, (c)
      another species of the same genus and (d) a species of a different genus. The
      mandible opening response (MOR) was recorded as the aggressive response. In all
      assayed species, MOR significantly differed among stimuli, being weakest towards
      nestmate odour and strongest towards odours originating from ants of a different
      genus. We thus introduce here a new procedure suitable for studying the chemical
      basis of aggression in ants.

PMID- 18344486
TI  - Aquaporins play a role in desiccation and freeze tolerance in larvae of the
      goldenrod gall fly, Eurosta solidaginis.
AB  - Survival of freezing not only requires organisms to tolerate ice formation within
      their body, but also depends on the rapid redistribution of water and
      cryoprotective compounds between intra- and extracellular compartments.
      Aquaporins are transmembrane proteins that serve as the major pathway through
      which water and small uncharged solutes (e.g. glycerol) enter and leave the cell.
      Consequently, we examined freeze-tolerant larvae of the goldenrod gall fly,
      Eurosta solidaginis, to determine whether aquaporins are present and if their
      presence promotes freeze tolerance of specific tissues. Immunoblotting with
      mammalian anti-AQP2, -AQP3 and -AQP4 revealed corresponding aquaporin homologues
      in E. solidaginis, whose patterns of expression varied depending on acclimation
      temperature and desiccation treatment. To examine the role of aquaporins in
      freeze tolerance, we froze fat body, midgut and salivary gland tissues in the
      presence and absence of mercuric chloride, an aquaporin inhibitor. Survival of
      fat body and midgut cells was significantly reduced when mercuric chloride was
      present. In contrast, survival of the salivary gland did not decrease when it was
      frozen with mercuric chloride. Overall, this study supports our hypothesis that
      naturally occurring aquaporins in E. solidaginis are regulated during desiccation
      and promote cell survival during freezing.

PMID- 18344487
TI  - Kinematics and power requirements of ascending and descending flight in the
      pigeon (Columba livia).
AB  - Ascending or descending locomotion involves a change in potential energy (PE) and
      a corresponding change in power requirement. We sought to test whether the
      mechanical power required for steady ascending or descending flight is a simple
      sum of the power required for level flight and the power necessary for potential
      energy change. Pigeons (Columba livia) were trained to fly at varying angles of
      ascent and descent (60 degrees , 30 degrees , 0 degrees , -30 degrees , -60
      degrees ), and were recorded using high-speed video. Detailed three-dimensional
      kinematics were obtained from the recordings, allowing analysis of wing movement.
      Aerodynamic forces and power requirements were then estimated from kinematic
      data. As expected, ;PE flight power' increased significantly with angle of flight
      (0.234 W deg.(-1)), though there appeared to be a limit on the amount of PE that
      the birds could gain or dissipate per wingbeat. We found that the total power
      output for flight at various angles was not different from the sum of power
      required for level flight and the PE rate of change for a given angle, except for
      the steep -60 degrees descent. The total power for steep descent was higher than
      this sum because of a higher induced power due to the bird's deceleration and
      slower flight velocity. Aerodynamic force estimates during mid-downstroke did not
      differ significantly in magnitude or orientation among flight angles. Pigeons
      flew fastest during -30 degrees flights (4.9+/-0.1 m s(-1)) and slowest at 60
      degrees (2.9+/-0.1 m s(-1)). Although wingbeat frequency ranged from 6.1 to 9.6
      Hz across trials, the variation was not significant across flight angles. Stroke
      plane angle was more horizontal, and the wing more protracted, for both +60
      degrees and -60 degrees flights, compared with other flight path angles.

PMID- 18344488
TI  - Matched regulation of gastrointestinal performance in the Burmese python, Python
      molurus.
AB  - In Burmese pythons fasting and feeding cause dramatic regulation of gastric acid
      production and intestinal nutrient uptake. Predictably, other components of their
      gastrointestinal tract are similarly regulated with each meal. We therefore
      assessed the matched regulation of gastrointestinal performance by comparing the
      postprandial activities and capacities of gastric (pepsin), pancreatic (amylase
      and trypsin) and intestinal (aminopeptidase-N and maltase) enzymes, and
      intestinal nutrient uptake. Tissue samples were collected from pythons fasted and
      at 0.25, 0.5, 1, 2, 3, 4, 6, 10 and 15 days following their consumption of rodent
      meals equaling 25% of snake body mass. With feeding, pythons experience no
      significant change in stomach mass, whereas both the pancreas and small intestine
      doubled in mass. Feeding also triggered a depletion of gastric mucosal
      pepsinogen, a respective 5.7- and 20-fold increase in the peak activities of
      pancreatic trypsin and amylase, and a respective 2.3- and 5.5-fold increase in
      the peak activities of intestinal maltase and aminopeptidase-N. Enzyme activities
      peaked between 2 and 4 days postfeeding and returned to fasting levels by day 10.
      Independent of digestive stage, python intestine exhibited a proximal to distal
      decline in enzyme activity. For both sugars and proteins, intestinal capacities
      for enzyme activity were significantly correlated with nutrient uptake
      capacities. The concomitant postprandial upregulation of tissue morphology,
      intestinal nutrient transport rates and enzyme activities illustrate, for the
      python, the matched regulation of their gastrointestinal performance with each
      meal.

PMID- 18344489
TI  - Recruitment of the diaphragmaticus, ischiopubis and other respiratory muscles to
      control pitch and roll in the American alligator (Alligator mississippiensis).
AB  - We used electromyography on juvenile American alligators to test the hypothesis
      that the following muscles, which are known to play a role in respiration, are
      recruited for aquatic locomotion: M. diaphragmaticus, M. ischiopubis, M. rectus
      abdominis, M. intercostalis internus, and the M. transversus abdominis. We found
      no activity with locomotion in the transversus. The diaphragmaticus, ischiopubis,
      rectus abdominis and internal intercostals were active when the animals executed
      a head-down dive from a horizontal posture. Weights attached to the base of the
      tail resulted in greater electrical activity of diaphragmaticus, ischiopubis and
      rectus muscles than when weights were attached to the head, supporting a role of
      this musculature in locomotion. The diaphragmaticus and rectus abdominis were
      active unilaterally with rolling maneuvers. Although the function of these
      muscles in locomotion has previously been unrecognized, these data raise the
      possibility that the locomotor function arose when Crocodylomorpha assumed a semi
      aquatic existence and that the musculoskeletal complex was secondarily recruited
      to supplement ventilation.

PMID- 18344490
TI  - Variability in forelimb bone strains during non-steady locomotor activities in
      goats.
AB  - The purpose of this study was to investigate the effects of non-steady locomotor
      activities on load predictability in two goat forelimb bones and to explore the
      degree to which bone curvature influences load predictability. We measured in
      vivo bone strains in the radius and metacarpus of juvenile goats performing a
      variety of natural behaviors in an outdoor arena and compared these strain
      magnitudes and loading patterns with those measured during steady-state treadmill
      locomotion. We sought to test two hypotheses: our first hypothesis expects an
      increase in the variability of strain magnitude and pattern during outdoor non
      steady behavior when compared to treadmill locomotion. Our second hypothesis was
      that the curved radius experiences higher peak strains but less variability
      during non-steady activities than the straighter metacarpus. We found that
      unsteady, outdoor locomotion generally caused more variable strain patterns
      (consistent with the first hypothesis), but not more variable strain magnitudes,
      than treadmill locomotion in both bones. During outdoor locomotion, higher
      magnitude strain events in the radius showed more constrained loading patterns
      than in the metacarpus (consistent with the second hypothesis). In addition to
      the radius experiencing significantly greater bending strains compared to the
      straighter metacarpus, these results support the idea of a trade-off between
      increased predictability of loading pattern and increased bending-induced strain.
      Strain magnitudes recorded during both outdoor and treadmill locomotion showed a
      lognormal frequency distribution, but the outdoor bone strain distributions had a
      greater range because they included high magnitude loading events that did not
      occur during steady treadmill locomotion.

PMID- 18344491
TI  - Identification of novel genes including Dermo-1, a marker of dermal
      differentiation, expressed in trout somitic external cells.
AB  - The external cell layer that surrounds the fish primary myotome provides the
      myogenic precursors necessary for muscle growth, suggesting that this epithelium
      is equivalent to the amniote dermomyotome. In this study we report the
      identification of a trout orthologue of the dermal marker Dermo-1, and show that
      trout somitic external cells, which are all potentially myogenic as indicated by
      the transcription of Pax7 gene, express Dermo-1. This finding and our previous
      observation that external cells express collagen I show that these cells have
      dermis-related characteristics in addition to exhibiting myogenic features. In an
      effort to identify novel genes expressed in the external cell epithelium we
      performed an in situ hybridisation screen and found both collectin sub-family
      member 12, a transmembrane C-type lectin, and Seraf, an EGF-like repeat autocrine
      factor. In situ hybridisation of staged trout embryos revealed that the
      expression of Dermo-1, collectin sub-family member 12 and Seraf within the
      external cell layer epithelium was preceded by a complex temporal and spatial
      expression pattern in the early somite.

PMID- 18344492
TI  - CXCL16 functions as a novel chemotactic factor for prostate cancer cells in
      vitro.
AB  - A variety of tumor cells produce chemokines that promote tumor cell proliferation
      and chemotaxis. We previously reported that CXCL16 production is increased in
      aggressive prostate cancer cells compared with the less aggressive tumor cells
      and benign cells as identified in a cytokine antibody array. The functional
      contribution of CXCL16 in prostate cancer development has not yet been evaluated.
      Accordingly, mRNA expression of CXCL16 and its receptor, CXCR6, were determined
      by real-time reverse transcription-PCR in various cancer cell lines, including
      prostate cancer and tissues obtained from localized and metastatic prostate
      cancer. Consistent with our finding on CXCL16 protein production by prostate
      cancer cells, aggressive prostate cancer C4-2B and PC3 cells, as well as bone and
      liver metastatic tissues, expressed higher levels of both CXCL16 and CXCR6 mRNA
      compared with the less aggressive prostate cancer LNCaP cells, nonneoplastic PrEC
      and RWPE-1 cells, and benign prostate tissues, respectively. Furthermore, CXCR6
      and CXCL16 protein expressions were examined in tissue specimens by
      immunohistochemistry. Immunohistochemical examination of CXCR6 expression showed
      strong epithelial staining that correlated with Gleason score, whereas CXCL16
      staining was not. Finally, we found that both interleukin-1beta and tumor
      necrosis factor alpha significantly induced CXCL16 production by prostate
      epithelial cells, thereby indicating that inflammatory cytokines may play a role
      in the CXCL16 induction. CXCL16 was found to promote prostate cancer cell
      migration and invasion in vitro. Therefore, we concluded that CXCL16 functions,
      through CXCR6, as a novel chemotactic factor for prostate cancer cells.

PMID- 18344493
TI  - Gene-viral cancer therapy using dual-regulated oncolytic adenovirus with
      antiangiogenesis gene for increased efficacy.
AB  - Conditionally replicative adenovirus (CRAD) represents a promising approach for
      cancer therapy. Several CRADs controlled by the human telomerase reverse
      transcriptase promoter have been developed. However, because of their replicative
      capacity, the importance of cancer specificity for CRADs needs to be further
      emphasized. In this study, we have developed a novel dual-regulated CRAD, CNHK500
      mE, which has its E1a and E1b gene controlled by the human telomerase reverse
      transcriptase promoter and the hypoxia response element, respectively. It also
      carries a mouse endostatin expression cassette controlled by the cytomegalovirus
      promoter. These properties allow for increased cancer cell targeting specificity
      and decreased adverse side effects. We showed that CNHK500-mE preferentially
      replicated in cancer cells. Compared with a replication-defective vector carrying
      the same endostatin expression cassette, CNHK500-mE-mediated transgene expression
      level was markedly increased via viral replication within cancer cells. In the
      nasopharyngeal tumor xenograft model, CNHK500-mE injection resulted in antitumor
      efficacy at day 7 after therapy. Three weeks later, it led to significant
      inhibition of xenograft tumor growth due to the combined effects of viral
      oncolytic therapy and antiangiogenesis gene therapy. Pathologic examination
      showed that most cancer cells were positive for adenoviral capsid protein and for
      apoptotic terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling
      in the CNHK500-mE-treated tumor tissues, and the microvessels in these tumor
      tissues were diminished in quantity and abnormal in morphology. These results
      suggest that, as a potential cancer therapeutic agent, the CNHK500-mE is endowed
      with higher specificity to cancer cells and low cytotoxicity to normal cells.

PMID- 18344494
TI  - Child maltreatment and substance abuse among U.S. Army soldiers.
AB  - Although substance abuse has consistently been linked to child maltreatment, no
      study to date has described the extent of substance abuse among child
      maltreatment offenders within the military. Analysis of U.S. Army data on all
      substantiated incidents of parental child maltreatment committed between 2000 and
      2004 by active duty soldiers found that 13% of offenders were noted to have been
      abusing alcohol or illicit drugs at the time of their child maltreatment
      incident. The odds of substance abuse were increased for offenders who committed
      child neglect or emotional abuse, but were reduced for child physical abuse. The
      odds of offender substance abuse nearly tripled in child maltreatment incidents
      that also involved co-occurring spouse abuse. Findings include a lack of
      association between offender substance abuse and child maltreatment recurrence,
      possibly because of the increased likelihood of removal of offenders from the
      home when either substance abuse or spouse abuse were documented.

PMID- 18344495
TI  - Coping with spousal loss: potential buffering effects of self-reported helping
      behavior.
AB  - The present study examined the role of self-reported helping behavior in
      attenuating the helper's depression following spousal loss. Using archival data
      from the Changing Lives of Older Couples sample (N = 289), the study shows that
      among bereaved participants who had experienced high loss-related grief, helping
      behavior (providing instrumental support to others) was associated with an
      accelerated decline in depressive symptoms for the helper from 6 months to 18
      months following spousal loss. This relationship between giving help and recovery
      from depression was independent of support received, as well as measured health,
      and interpersonal and demographic factors. Implications of these results for
      theoretical approaches to the study of close relationships and well-being are
      discussed.

PMID- 18344496
TI  - Should persuasion be affective or cognitive? The moderating effects of need for
      affect and need for cognition.
AB  - Three experiments tested the hypothesis that need for affect and need for
      cognition influence receptivity to affect- and cognition-based persuasive
      messages. Experiment 1 found that an affective message elicited more positive
      attitudes among individuals high in need for affect and low in need for
      cognition, whereas a cognitive message elicited more positive attitudes among
      individuals low in need for affect and high in need for cognition. Experiment 2
      found that individual differences in need for affect influenced receptivity to an
      affect-based (but not cognition-based) message, whereas individual differences in
      need for cognition influenced receptivity to a cognition-based (but not affect
      based) message. Experiment 3 found that individual differences in need for affect
      were associated with increased recognition of information from an affect-based
      (but not cognition-based) message, whereas individual differences in need for
      cognition were associated with increased recognition of information from a
      cognition-based (but not affect-based) message. Overall, the studies point to the
      importance of individual differences in need for affect and need for cognition in
      understanding how individuals respond to different types of persuasive messages.

PMID- 18344497
TI  - Elimination of porcine reproductive and respiratory syndrome virus from a
      seedstock breeding farm and a supplying boar stud by a modified test and removal
      method.
AB  - To eliminate porcine reproductive and respiratory syndrome virus (PRRSV) from a
      supplying boar stud, samples of serum and semen from 118 boars were assessed
      three times a month by an indirect fluorescent antibody (IFA) test to detect
      antibodies, and by a nested reverse transcriptase-PCR (nRT-PCR) to detect the
      genome of PRRSV. The boars detected as persistently infected carriers were
      culled. A PRRSV-negative population of boars was established after three months
      and no semen positive for the virus was detected for six months. Subsequently, a
      three-step plan was introduced to eliminate PRRSV from the seedstock breeding
      farm during three parity cycles on the farm over 15 months, each step taking five
      months. In step 1, umbilical cords taken from piglets at birth and serum samples
      taken from their dams at the start of weaning were subjected to ifa and nRT-pcr
      analysis. The sows with PRRSV detected in serum by nRT-pcr were regarded as
      carrier sows and culled. The rates of detection of PRRSV were reduced from 5
      percent to 2.5 percent in the sera of the sows, and from 14.8 percent to 1.8
      percent in the umbilical cords of the piglets. In step 2, the sows that had
      farrowed the piglets with PRRSV detected by nRT-PCR in their cords were
      considered to have transmitted the infection and removed. During step 2, the
      virus detection rates in umbilical cords by nRT-pcr were reduced, but not
      completely eliminated. In step 3, 10-week-old nursery pigs with antibodies to
      PRRSV in their serum by ifa and elisa were culled. The three steps established
      the PRRSV-negative state of the multisite farm containing the breeding and
      nursery farm, and the PRRSV-negative state of both the multisite farm and the
      supplying boar stud was evaluated by monthly monitoring over at least one parity
      cycle of the farm for five months.

PMID- 18344498
TI  - Clinical, serological and molecular investigations of EHV-1 and EHV-4 in 15
      unweaned thoroughbred foals.
AB  - Fifteen unweaned thoroughbred foals, born on a stud farm to vaccinated mares,
      were clinically monitored during their first six months of life and repeatedly
      tested for equine herpesvirus type 1 (EHV-1) and equine herpesvirus type 4 (EHV
      4). Nasopharyngeal swabs and blood samples were collected and screened
      respectively by PCR and seroneutralisation to detect the presence of the virus,
      explore its role as a possible cause of respiratory disease, and to assess the
      efficiency of the pcr for the diagnosis of this disease. The foals were divided
      into three groups on the basis of their clinical signs and whether they had
      seroconverted to EHV-1 and/or EHV-4: first, foals with no clinical signs of
      disease that had not seroconverted; secondly, foals with clinical signs that had
      seroconverted, and thirdly, foals with clinical signs that had not seroconverted.
      The results indicated that the viruses circulated on the stud farm despite
      stringent vaccination regimens against them, and confirmed their association with
      respiratory disease. The absence of significantly different pcr results among the
      three groups of foals showed that the pcr was effective in confirming the
      circulation of the viruses on the premises without being particularly helpful as
      a diagnostic tool.

PMID- 18344499
TI  - Plasma concentrations of 25-hydroxycholecalciferol in 22 captive tortoises
      (Testudo species).
AB  - The plasma concentration of 25-hydroxycholecalciferol was measured in 13 adult
      Hermann's tortoises (Testudo hermanni), seven adult spur-thighed tortoises
      (Testudo graeca) and two adult marginated tortoises (Testudo marginata) during
      2004. They were healthy, of both sexes, and kept in captivity under natural
      unfiltered sunlight in southern England with no dietary sources of
      cholecalciferol. Blood samples were taken in March, June and August, and the
      concentration of 25-hydroxycholecalciferol did not vary significantly with the
      seasons. However, the concentrations in the female tortoises were always
      significantly lower than in the males.

PMID- 18344500
TI  - Levels of parasitism on organic and non-organic dairy farms in Scotland.

PMID- 18344501
TI  - Facial cellulitis due to Actinobacillus equuli infection in a neonatal foal.

PMID- 18344502
TI  - Fatal dystocia in a giraffe due to a pelvic chondrosarcoma.

PMID- 18344503
TI  - Polyostotic bone lesions consistent with bone infarction in a horse.

PMID- 18344504
TI  - Handling of the 2007 FMD outbreak: 'much to applaud...some deficiencies'.

PMID- 18344505
TI  - Suicide by veterinary surgeons.

PMID- 18344506
TI  - Veterinary voice.

PMID- 18344507
TI  - Modification of the rules of racing.

PMID- 18344508
TI  - Non-suppurative meningoencephalitis of greyhounds.

PMID- 18344509
TI  - Cost sharing on animal health.

PMID- 18344510
TI  - Eczema, birth order, and infection.
AB  - The association between infections occurring in the first 2 years of life and
      development of eczema was investigated in 1,782 control children from a national
      population-based case-control study in the United Kingdom conducted over the
      period 1991-1996. Dates of eczema and infectious diagnoses were ascertained from
      contemporaneously collected primary care records. Children diagnosed with eczema
      before the age of 2 years had more prior clinically diagnosed infections recorded
      than did children without eczema (rate ratio = 1.26, 95% confidence interval
      (CI): 1.18, 1.36). The difference in infection rates between children with and
      without eczema was apparent from birth and throughout the first 2 years of life.
      As expected, compared with children of second or higher birth order, those
      firstborn were at increased risk of eczema (p = 0.020); however, the relation
      between eczema and prior infection was evident only among children of second or
      higher birth order and not among firstborn children (rate ratio = 1.45, 95% CI:
      1.32, 1.59, and rate ratio = 1.08, 95% CI: 0.98, 1.20, respectively). The
      authors' results are consistent with the notion that the association between
      birth order and eczema is unlikely to be attributable to variations in early
      infectious exposure.

PMID- 18344511
TI  - Re: "Body size, weight cycling, and risk of renal cell carcinoma among
      postmenopausal women: the women's health initiative (United States)".

PMID- 18344512
TI  - Invited commentary: measuring social disparities in health--what was the question
      again?
AB  - Monitoring social disparities in health is not a straightforward project.
      Defining what constitutes a disparity is challenging, and multiple measures have
      been proposed to track changes in disparity over time. In this issue, Harper et
      al. (Am J Epidemiol 2008;167:889-899) present seven health disparity measures and
      apply them to US lung cancer incidence rates (1992-2004). They find that
      different summary measures provide different answers to the question "Has
      disparity increased or decreased?" Their findings leave us uncertain how to use
      and interpret these measures to track changes in social disparities in health. In
      this invited commentary, the author proposes that increased attention to the
      scale at which disparities are measured, the interpretations attached to the
      various measures used, and the way in which these measures are assembled on the
      basis of conceptual models would benefit the field. Specifically, attention to
      these three areas would increase the capacity to communicate research findings to
      the public and policy-making consumers of disparity-related research.

PMID- 18344513
TI  - An overview of methods for monitoring social disparities in cancer with an
      example using trends in lung cancer incidence by area-socioeconomic position and
      race-ethnicity, 1992-2004.
AB  - The authors provide an overview of methods for summarizing social disparities in
      health using the example of lung cancer. They apply four measures of relative
      disparity and three measures of absolute disparity to trends in US lung cancer
      incidence by area-socioeconomic position and race-ethnicity from 1992 to 2004.
      Among females, measures of absolute and relative disparity suggested that area
      socioeconomic and race-ethnic disparities increased over these 12 years but
      differed widely with respect to the magnitude of the change. Among males, the
      authors found substantial disagreement among summary measures of relative
      disparity with respect to the magnitude and the direction of change in
      disparities. Among area-socioeconomic groups, the index of disparity increased by
      47% and the relative concentration index decreased by 116%, while for race
      ethnicity the index of disparity increased by 36% and the Theil index increased
      by 13%. The choice of a summary measure of disparity may affect the
      interpretation of changes in health disparities. Important issues to consider are
      the reference point from which differences are measured, whether to measure
      disparity on the absolute or relative scale, and whether to weight disparity
      measures by population size. A suite of indicators is needed to provide a clear
      picture of health disparity change.

PMID- 18344514
TI  - Re: "Using head-on collisions to compare risk of driver death by frontal air bag
      generation: a matched-pair cohort study".

PMID- 18344515
TI  - A prospective study of multivitamin supplement use and risk of breast cancer.
AB  - The authors evaluated the association between multivitamin supplement use and
      breast cancer risk in a completed trial. At baseline (1992-1995), 37,920 US women
      aged > or =45 years and free of cancer provided detailed information on
      multivitamin supplement use. During an average of 10 years of follow-up, 1,171
      cases of invasive breast cancer were documented. Multivitamin use was not
      significantly associated with overall risk of breast cancer. Compared with the
      risk for never users, the multivariable relative risks were 0.97 (95% confidence
      interval: 0.81, 1.16) for past users and 0.99 (95% confidence interval: 0.82,
      1.19) for current users. Current multivitamin use for > or =20 years or > or =6
      times/week was also not significantly associated with risk. Multivitamin use was
      nonsignificantly inversely associated with risk of breast cancer among women
      consuming > or =10 g/day of alcohol and with risk of estrogen receptor negative
      progesterone receptor negative breast cancer. Multivitamin use was
      nonsignificantly associated with a reduced risk of developing < or =2-cm breast
      tumors but an increased risk of >2-cm tumors. The authors' data indicate no
      overall association between multivitamin use and breast cancer risk but suggest
      that multivitamin use might reduce risk for women consuming alcohol or decrease
      risk of estrogen receptor negative-progesterone receptor negative breast cancer.

PMID- 18344516
TI  - Use of recovery biomarkers to calibrate nutrient consumption self-reports in the
      Women's Health Initiative.
AB  - Underreporting of energy consumption by self-report is well-recognized, but
      previous studies using recovery biomarkers have not been sufficiently large to
      establish whether participant characteristics predict misreporting. In 2004-2005,
      544 participants in the Women's Health Initiative Dietary Modification Trial
      completed a doubly labeled water protocol (energy biomarker), 24-hour urine
      collection (protein biomarker), and self-reports of diet (assessed by food
      frequency questionnaire (FFQ)), exercise, and lifestyle habits; 111 women
      repeated all procedures after 6 months. Using linear regression, the authors
      estimated associations of participant characteristics with misreporting, defined
      as the extent to which the log ratio (self-reported FFQ/nutritional biomarker)
      was less than zero. Intervention women in the trial underreported energy intake
      by 32% (vs. 27% in the comparison arm) and protein intake by 15% (vs. 10%).
      Younger women had more underreporting of energy (p = 0.02) and protein (p =
      0.001), while increasing body mass index predicted increased underreporting of
      energy and overreporting of percentage of energy derived from protein (p = 0.001
      and p = 0.004, respectively). Blacks and Hispanics underreported more than did
      Caucasians. Correlations of initial measures with repeat measures (n = 111) were
      0.72, 0.70, 0.46, and 0.64 for biomarker energy, FFQ energy, biomarker protein,
      and FFQ protein, respectively. Recovery biomarker data were used in regression
      equations to calibrate self-reports; the potential application of these equations
      to disease risk modeling is presented. The authors confirm the existence of
      systematic bias in dietary self-reports and provide methods of correcting for
      measurement error.

PMID- 18344517
TI  - GlycoBase and autoGU: tools for HPLC-based glycan analysis.
AB  - SUMMARY: The development of robust high-performance liquid chromatography (HPLC)
      technologies continues to improve the detailed analysis and sequencing of glycan
      structures released from glycoproteins. Here, we present a database (GlycoBase)
      and analytical tool (autoGU) to assist the interpretation and assignment of HPLC
      glycan profiles. GlycoBase is a relational database which contains the HPLC
      elution positions for over 350 2-AB labelled N-glycan structures together with
      predicted products of exoglycosidase digestions. AutoGU assigns provisional
      structures to each integrated HPLC peak and, when used in combination with
      exoglycosidase digestions, progressively assigns each structure automatically
      based on the footprint data. These tools are potentially very promising and
      facilitate basic research as well as the quantitative high-throughput analysis of
      low concentrations of glycans released from glycoproteins. AVAILABILITY:
      http://glycobase.ucd.ie

PMID- 18344518
TI  - Unequal group variances in microarray data analyses.
AB  - MOTIVATION: In searching for differentially expressed (DE) genes in microarray
      data, we often observe a fraction of the genes to have unequal variability
      between groups. This is not an issue in large samples, where a valid test exists
      that uses individual variances separately. The problem arises in the small-sample
      setting, where the approximately valid Welch test lacks sensitivity, while the
      more sensitive moderated t-test assumes equal variance. METHODS: We introduce a
      moderated Welch test (MWT) that allows unequal variance between groups. It is
      based on (i) weighting of pooled and unpooled standard errors and (ii) improved
      estimation of the gene-level variance that exploits the information from across
      the genes. RESULTS: When a non-trivial proportion of genes has unequal
      variability, false discovery rate (FDR) estimates based on the standard t and
      moderated t-tests are often too optimistic, while the standard Welch test has low
      sensitivity. The MWT is shown to (i) perform better than the standard t, the
      standard Welch and the moderated t-tests when the variances are unequal between
      groups and (ii) perform similarly to the moderated t, and better than the
      standard t and Welch tests when the group variances are equal. These results mean
      that MWT is more reliable than other existing tests over wider range of data
      conditions. AVAILABILITY: R package to perform MWT is available at
      http://www.meb.ki.se/~yudpaw

PMID- 18344519
TI  - Tissue inhibitor of metalloproteinases-3 interacts with angiotensin II type 2
      receptor and additively inhibits angiogenesis.
AB  - AIM: The tissue inhibitors of metalloproteinases (TIMPs) are complex molecules
      with both pro- and anti-tumour effects. Thus, their diverse expression could be
      because of their multifunctional properties with respect to tumour growth,
      angiogenesis, apoptosis, and other biological functions. Previous data have shown
      that TIMPs bind tightly to most matrix metalloproteinases, although the pathway
      that mediates angiostatic activity has not been fully established. METHODS AND
      RESULTS: As an initial step to elucidate the mechanism that regulates TIMP-3, we
      used a yeast two-hybrid system to screen a human ovary cDNA library for a novel
      TIMP-3-interacting partner. Here, we identified human angiotensin II type 2
      receptor (AGTR2) as such a partner, which is well known to be a regulator of
      cardiovascular homoeostasis. In this present study, we investigated whether AGTR2
      mediated apoptotic activity can inhibit the growth of ovarian cancer in an
      experimental model system. AGTR2 treatment was found to be more effective in
      inhibiting ovarian cancer growth than the treatment with TIMP-3 in parallel
      experiments. Subsequently, the efficacy of the combined treatment with TIMP-3 and
      AGTR2 was investigated. In the presence of both of these proteins, vascular
      endothelial growth factor-induced human umbilical vein endothelial cell
      proliferation was additively inhibited, and the inhibition of Akt and endothelial
      NO synthase phosphorylation was blocked. CONCLUSION: These combined results
      suggest that two angiostatic molecules may have an important biological role in
      regulating potent anti-angiogenic effects and possibly may have a role in anti
      tumour therapy.

PMID- 18344520
TI  - Determinants of a transcriptionally competent environment at the GM-CSF promoter.
AB  - Granulocyte macrophage-colony stimulating factor (GM-CSF) is produced by T cells,
      but not B cells, in response to immune signals. GM-CSF gene activation in
      response to T-cell stimulation requires remodelling of chromatin associated with
      the gene promoter, and these changes do not occur in B cells. While the CpG
      methylation status of the murine GM-CSF promoter shows no correlation with the
      ability of the gene to respond to activation, we find that the basal chromatin
      environment of the gene promoter influences its ability to respond to immune
      signals. In unstimulated T cells but not B cells, the GM-CSF promoter is
      selectively marked by enrichment of histone acetylation, and association of the
      chromatin-remodelling protein BRG1. BRG1 is removed from the promoter upon
      activation concomitant with histone depletion and BRG1 is required for efficient
      chromatin remodelling and transcription. Increasing histone acetylation at the
      promoter in T cells is paralleled by increased BRG1 recruitment, resulting in
      more rapid chromatin remodelling, and an associated increase in GM-CSF mRNA
      levels. Furthermore, increasing histone acetylation in B cells removes the block
      in chromatin remodelling and transcriptional activation of the GM-CSF gene. These
      data are consistent with a model in which histone hyperacetylation and BRG1
      enrichment at the GM-CSF promoter, generate a chromatin environment competent to
      respond to immune signals resulting in gene activation.

PMID- 18344521
TI  - Sensitive Melting Analysis after Real Time- Methylation Specific PCR (SMART-MSP):
      high-throughput and probe-free quantitative DNA methylation detection.
AB  - DNA methylation changes that are recurrent in cancer have generated great
      interest as potential biomarkers for the early detection and monitoring of
      cancer. In such situations, essential information is missed if the methylation
      detection is purely qualitative. We describe a new probe-free quantitative
      methylation-specific PCR (MSP) assay that incorporates evaluation of the amplicon
      by high-resolution melting (HRM) analysis. Depending on amplicon design,
      different types of information can be obtained from the HRM analysis. Much of
      this information cannot be obtained by electrophoretic analysis. In particular,
      identification of false positives due to incomplete bisulphite conversion or
      false priming is possible. Heterogeneous methylation can also be distinguished
      from homogeneous methylation. As proof of principle, we have developed assays for
      the promoter regions of the CDH1, DAPK1, CDKN2A (p16(INK4a)) and RARB genes. We
      show that highly accurate quantification is possible in the range from 100% to
      0.1% methylated template when 25 ng of bisulphite-modified DNA is used as a
      template for PCR. We have named this new approach to quantitative methylation
      detection, Sensitive Melting Analysis after Real Time (SMART)-MSP.

PMID- 18344522
TI  - Labeling of unique sequences in double-stranded DNA at sites of vicinal nicks
      generated by nicking endonucleases.
AB  - We describe a new approach for labeling of unique sequences within dsDNA under
      nondenaturing conditions. The method is based on the site-specific formation of
      vicinal nicks, which are created by nicking endonucleases (NEases) at specified
      DNA sites on the same strand within dsDNA. The oligomeric segment flanked by both
      nicks is then substituted, in a strand displacement reaction, by an
      oligonucleotide probe that becomes covalently attached to the target site upon
      subsequent ligation. Monitoring probe hybridization and ligation reactions by
      electrophoretic mobility retardation assay, we show that selected target sites
      can be quantitatively labeled with excellent sequence specificity. In these
      experiments, predominantly probes carrying a target-independent 3' terminal
      sequence were employed. At target labeling, thus a branched DNA structure known
      as 3'-flap DNA is obtained. The single-stranded terminus in 3'-flap DNA is then
      utilized to prime the replication of an externally supplied ssDNA circle in a
      rolling circle amplification (RCA) reaction. In model experiments with samples
      comprised of genomic lambda-DNA and human herpes virus 6 type B (HHV-6B) DNA, we
      have used our labeling method in combination with surface RCA as reporter system
      to achieve both high sequence specificity of dsDNA targeting and high sensitivity
      of detection. The method can find applications in sensitive and specific
      detection of viral duplex DNA.

PMID- 18344523
TI  - A space-efficient and accurate method for mapping and aligning cDNA sequences
      onto genomic sequence.
AB  - The mapping and alignment of transcripts (cDNA, expressed sequence tag or amino
      acid sequences) onto a genomic sequence is a fundamental step for genome
      annotation, including gene finding and analyses of transcriptional activity,
      alternative splicing and nucleotide polymorphisms. As DNA sequence data of
      genomes and transcripts are accumulating at an unprecedented rate, steady
      improvement in accuracy, speed and space requirement in the computational tools
      for mapping/alignment is desired. We devised a multi-phase heuristic algorithm
      and implemented it in the development of the stand-alone computer program Spaln
      (space-efficient spliced alignment). Spaln is reasonably fast and space
      efficient; it requires <1 Gb of memory to map and align >120 000 Unigene
      sequences onto the unmasked whole human genome with a conventional computer,
      finishing the job in <6 h. With artificially introduced noise of various levels,
      Spaln significantly outperforms other leading alignment programs currently
      available with respect to the accuracy of mapped exon-intron structures. This
      performance is achieved without extensive learning procedures to adjust parameter
      values to a particular organism. According to the handiness and accuracy, Spaln
      may be used for studies on a wide area of genome analyses.

PMID- 18344524
TI  - High-resolution array comparative genomic hybridization of single micrometastatic
      tumor cells.
AB  - Only few selected cancer cells drive tumor progression and are responsible for
      therapy resistance. Their specific genomic characteristics, however, are largely
      unknown because high-resolution genome analysis is currently limited to DNA
      pooled from many cells. Here, we describe a protocol for array comparative
      genomic hybridization (array CGH), which enables the detection of DNA copy number
      changes in single cells. Combining a PCR-based whole genome amplification method
      with arrays of highly purified BAC clones we could accurately determine known
      chromosomal changes such as trisomy 21 in single leukocytes as well as complex
      genomic imbalances of single cell line cells. In single T47D cells aberrant
      regions as small as 1-2 Mb were identified in most cases when compared to non
      amplified DNA from 10(6) cells. Most importantly, in single micrometastatic
      cancer cells isolated from bone marrow of breast cancer patients, we retrieved
      and confirmed amplifications as small as 4.4 and 5 Mb. Thus, high-resolution
      genome analysis of single metastatic precursor cells is now possible and may be
      used for the identification of novel therapy target genes.

PMID- 18344525
TI  - A new kinetic model reveals the synergistic effect of E-, P- and A-sites on +1
      ribosomal frameshifting.
AB  - Programmed ribosomal frameshifting (PRF) is a process by which ribosomes produce
      two different polypeptides from the same mRNA. In this study, we propose three
      different kinetic models of +1 PRF, incorporating the effects of the ribosomal E
      , P- and A-sites toward promoting efficient +1 frameshifting in Escherichia coli.
      Specifically, the timing of E-site tRNA dissociation is discussed within the
      context of the kinetic proofreading mechanism of aminoacylated tRNA (aa-tRNA)
      selection. Mathematical modeling using previously determined kinetic rate
      constants reveals that destabilization of deacylated tRNA in the E-site,
      rearrangement of peptidyl-tRNA in the P-site, and availability of cognate aa-tRNA
      corresponding to the A-site act synergistically to promote efficient +1 PRF. The
      effect of E-site codon:anticodon interactions on +1 PRF was also experimentally
      examined with a dual fluorescence reporter construct. The combination of
      predictive modeling and empirical testing allowed the rate constant for P-site
      tRNA slippage (k(s)) to be estimated as k(s) approximately 1.9 s(-1) for the
      release factor 2 (RF2) frameshifting sequence. These analyses suggest that P-site
      tRNA slippage is the driving force for +1 ribosomal frameshifting while the
      presence of a 'hungry codon' in the A-site and destabilization in the E-site
      further enhance +1 PRF in E. coli.

PMID- 18344526
TI  - Metabolite profiling reveals distinct changes in carbon and nitrogen metabolism
      in phosphate-deficient barley plants (Hordeum vulgare L.).
AB  - Plants modify metabolic processes for adaptation to low phosphate (P) conditions.
      Whilst transcriptomic analyses show that P deficiency changes hundreds of genes
      related to various metabolic processes, there is limited information available
      for global metabolite changes of P-deficient plants, especially for cereals. As
      changes in metabolites are the ultimate 'readout' of changes in gene expression,
      we profiled polar metabolites from both shoots and roots of P-deficient barley
      (Hordeum vulgare) using gas chromatography-mass spectrometry (GC-MS). The results
      showed that mildly P-deficient plants accumulated di- and trisaccharides
      (sucrose, maltose, raffinose and 6-kestose), especially in shoots. Severe P
      deficiency increased the levels of metabolites related to ammonium metabolism in
      addition to di- and trisaccharides, but reduced the levels of phosphorylated
      intermediates (glucose-6-P, fructose-6-P, inositol-1-P and glycerol-3-P) and
      organic acids (alpha-ketoglutarate, succinate, fumarate and malate). The results
      revealed that P-deficient plants modify carbohydrate metabolism initially to
      reduce P consumption, and salvage P from small P-containing metabolites when P
      deficiency is severe, which consequently reduced levels of organic acids in the
      tricarboxylic acid (TCA) cycle. The extent of the effect of severe P deficiency
      on ammonium metabolism was also revealed by liquid chromatography-mass
      spectrometry (LC-MS) quantitative analysis of free amino acids. A sharp increase
      in the concentrations of glutamine and asparagine was observed in both shoots and
      roots of severely P-deficient plants. Based on these data, a strategy for
      improving the ability of cereals to adapt to low P environments is proposed that
      involves alteration in partitioning of carbohydrates into organic acids and amino
      acids to enable more efficient utilization of carbon in P-deficient plants.

PMID- 18344527
TI  - Protein polymorphism between 2 Picea abies populations revealed by 2-dimensional
      gel electrophoresis and tandem mass spectrometry.
AB  - In species with high gene flow and consequent low interpopulation differentiation
      over wide geographic ranges, differential gene expression along ecological
      gradients often reveals adaptive significance. We investigated potential
      differences in protein expression between Picea abies ecotypes adapted to
      contrasting altitude conditions. Protein expression patterns were compared
      between needles and roots of 2-month-old P. abies seedlings by means of 2
      dimensional electrophoresis. Proteins exhibiting differential expression between
      the 2 ecotypes were analyzed by tandem mass spectrometry. A total of 19 proteins
      exhibited qualitative or quantitative polymorphism between the 2 populations.
      These proteins exhibited organ-specific expression, and the level of
      interpopulation protein polymorphism was organ dependent. Among differentially
      expressed proteins, we identified proteins involved in photosynthesis,
      photorespiration, root tracheary element differentiation, and transmitochondrial
      membrane transport. Our results show that P. abies seedlings from locally adapted
      ecotypes exhibit consistent differences in protein expression. The expression
      polymorphism of some of these proteins has potential adaptive significance.

PMID- 18344528
TI  - Defining the assumptions underlying modeling of epistatic QTL using variance
      component methods.
AB  - Variance component models are commonly used to detect quantitative trait loci
      (QTL) in general pedigrees. The variance-covariance structure of the random QTL
      effect is given by the identity by descent (IBD) between genotypes. Epistatic
      effects have previously been modeled, both for unlinked and linked loci, as a
      random effect with a variance-covariance structure given by the Hadamard product
      between the IBD matrices of the direct QTL effects. In the original papers, the
      model was given but not derived. Here, we identify the underlying assumptions of
      this previously proposed model. It assumes that either an unlinked QTL or a fully
      informative marker (i.e., all marker alleles are unique in the base generation)
      is located between the loci. We discuss the need of developing a general
      algorithm to estimate the variance-covariance structure of the random epistatic
      effect for linked loci.

PMID- 18344529
TI  - Molecular aspects of Anthocyanin fruit tomato in relation to high pigment-1.
AB  - The tomato Anthocyanin fruit (Aft) genotype is characterized by purple color in
      skin and outer pericarp of its fruits due to higher levels of anthocyanins
      flavonoid metabolites. Our objectives were to carry out metabolic and molecular
      characterization of this genotype, emphasizing its interaction with the high
      pigment-1 (hp-1) mutation, known to increase flavonoids in tomato fruits. These
      objectives fit the growing interest in developing tomato fruits with higher
      levels of functional metabolites. Our results show that 1) Aft fruits are also
      characterized by significantly higher levels of the flavonols quercetin and
      kaempferol, thus enhancing their functional value; 2) the tomato Anthocyanin1
      (Ant1) gene, encoding a Myb transcription factor, displayed nucleotide and amino
      acid polymorphisms between the Aft genotype and cultivated genotypes; 3) a DNA
      marker based on Ant1 showed that the Aft trait is encoded by a single locus on
      chromosome 10 fully associated with Ant1; and 4) double homozygotes Aft/Aft hp
      1/hp-1 plants displayed a more-than-additive effect on the production of fruit
      anthocyanidins and flavonols. This effect was manifested by approximately 5-, 19
      , and 33-fold increase of petunidin, malvidin, and delphinidin, respectively, in
      the double mutants compared with the cumulative levels of their parental lines.

PMID- 18344530
TI  - In vitro assessment of mitochondrial dysfunction and cytotoxicity of nefazodone,
      trazodone, and buspirone.
AB  - Mitochondrial toxicity is increasingly implicated in a host of drug-induced organ
      toxicities, including hepatotoxicity. Nefazodone was withdrawn from the U.S.
      market in 2004 due to hepatotoxicity. Accordingly, we evaluated nefazodone,
      another triazolopyridine trazodone, plus the azaspirodecanedione buspirone, for
      cytotoxicity and effects on mitochondrial function. In accord with its clinical
      disposition, nefazodone was the most toxic compound of the three, trazodone had
      relatively modest effects, whereas buspirone showed the least toxicity.
      Nefazodone profoundly inhibited mitochondrial respiration in isolated rat liver
      mitochondria and in intact HepG2 cells where this was accompanied by simultaneous
      acceleration of glycolysis. Using immunocaptured oxidative phosphorylation
      (OXPHOS) complexes, we identified Complex 1, and to a lesser amount Complex IV,
      as the targets of nefazodone toxicity. No inhibition was found for trazodone, and
      buspirone showed 3.4-fold less inhibition of OXPHOS Complex 1 than nefazodone. In
      human hepatocytes that express cytochrome P450, isoform 3A4, after 24 h exposure,
      nefazodone and trazodone collapsed mitochondrial membrane potential, and imposed
      oxidative stress, as detected via glutathione depletion, leading to cell death.
      Our results suggest that the mitochondrial impairment imposed by nefazodone is
      profound and likely contributes to its hepatotoxicity, especially in patients
      cotreated with other drugs with mitochondrial liabilities.

PMID- 18344531
TI  - Tissue exposures to free and glucuronidated monobutylyphthalate in the pregnant
      and fetal rat following exposure to di-n-butylphthalate: evaluation with a PBPK
      model.
AB  - Human exposure to phthalic acid diesters occurs through a variety of pathways as
      a result of their widespread use in plastics. Repeated doses of di-n
      butylphthalate (DBP) from gestation day (GD) 12 to 19 disrupt testosterone
      synthesis and male sexual development in the fetal rat. To gain a better
      understanding of the relationship of the target tissue (testes) dose to observed
      developmental effects, the pharmacokinetics of monobutyl phthalate (MBP) and its
      glucuronide (MBP-G) were examined in pregnant and fetal rats following single and
      repeated administration of DBP from GD 12-19. These data, together with results
      from previously published studies, were used to develop a physiologically based
      pharmacokinetic model for DBP and its metabolites in the male, pregnant and fetal
      rat. The model structure accounts for the major metabolic (hydrolysis,
      glucuronidation, oxidative metabolism) and transport processes (enterohepatic
      recirculation, urinary and fecal excretion, placental transfer). Extrapolation of
      the validated adult male rat model to gestation successfully predicts MBP and MBP
      G levels in maternal plasma, placenta and urine, as well as the fetal plasma and
      testes. Sensitivity analysis indicates that plasma MBP kinetics are particularly
      sensitive to glucuronidation and enterohepatic recirculation: a decrease in the
      uridine 5'-diphospho-glucuronosyltransferase (UDPGT) capacity during gestation
      results in an increased MBP residence time, and saturation of UDPGT at the
      highest doses (> 100 mg/kg/day) causes a flattening out of the plasma time course
      data. Oxidative metabolism plays a significant role in elimination only at low
      doses (< 50 mg/kg DBP). Insights gained from modeling of the rat data will be
      used to support development of a human PBPK model for DBP.

PMID- 18344533
TI  - Usage of air monitoring and biomarkers of isocyanate exposure to assess the
      effect of a control intervention.
AB  - Exposure to isocyanates is known to have respiratory effects in workers and
      therefore it is essential to monitor the occupational exposure. An earlier study
      of a continuous foaming plant using toluene diisocyanate (TDI) showed that the
      exposure to isocyanates can be high. Since then several preventive actions were
      implemented at the plant. The aim of this study was to observe the effect of
      these actions measured by air and biological monitoring. Four workers were
      monitored in the year 2000 and six in 2005, with air measurements during the
      continuous foaming process, and with measurements of biomarkers in one plasma
      sample each year and with two urinary samples being collected in the year 2000
      and one in 2005. The median TDI air concentrations in 2005 were approximately 20%
      of the 2000 levels and the median levels of biomarkers in 2005 were approximately
      10% of the 2000 levels. According to our measurements the preventive action had a
      real effect to decrease the exposure to TDI. As the workers both before and after
      the preventive actions used personal protective equipment, the use of biomarkers
      was necessary to assess the real gain in the preventive actions.

PMID- 18344534
TI  - Health survey of workers exposed to mixed solvent and ergonomic hazards in
      footwear and equipment factory workers in Thailand.
AB  - A cross-sectional health study was performed at four footwear and one equipment
      factory in Thailand to evaluate the prevalence of chemical- and ergonomic-related
      symptoms in Thai factory workers and to investigate associations between these
      symptoms and exposures to organic solvents, isocyanates and ergonomic risks. A 10
      page health questionnaire was administered to 1784 workers across the four
      footwear and equipment factories. A total of 1675 questionnaires were returned,
      yielding a 94% response rate. The questionnaires asked about age, gender, use of
      chemicals, use of personal protective equipment and health outcomes. Without
      exception, the percentages of workers reporting symptoms after being hired were
      higher than those reporting symptoms before being hired for all the factories.
      The highest symptom percentages were related to ergonomic stressors. Multiple
      logistic regression was used to calculate adjusted prevalence odds ratios and 95%
      confidence intervals. This study showed that adverse health effects experienced
      by footwear and equipment factory workers are associated with occupational
      exposures to chemicals (volatile organic solvents and water-based adhesives) and
      ergonomic hazards.

PMID- 18344535
TI  - Report of an international expanded access program of imatinib in adults with
      Philadelphia chromosome positive leukemias.
AB  - BACKGROUND: Imatinib is a selective inhibitor of the BCR/ABL tyrosine kinase. The
      remarkable initial results of the first phase I clinical trial published in 1999
      prompted the rapid initiation of large phase II trials. They also generated
      intense media coverage and significant interest from patients and clinicians and
      demand for access to imatinib before marketing approval. In response, a worldwide
      expanded access program (EAP) for imatinib was implemented in May 2000. PATIENTS:
      In total, 7380 patients with chronic myeloid leukemia (CML) and acute
      lymphoblastic leukemia failing prior therapies were enrolled in 106 centers in 34
      countries. RESULTS: Time to progression and overall survival, as well as the
      safety profile, were similar to those observed in published phase II studies. At
      the end of the program, patients benefiting from treatment were continued on
      imatinib therapy by transferring to national health care systems or patient
      assistance programs. CONCLUSION: The imatinib EAP successfully provided therapy
      to patients with CML before marketing approval. The program provides an efficient
      framework for the development of global EAPs for innovative investigational
      anticancer agents in patients without a satisfactory therapeutic alternative.

PMID- 18344536
TI  - Immunochemotherapy with in vivo purging and autotransplant induces long clinical
      and molecular remission in advanced relapsed and refractory follicular lymphoma.
AB  - BACKGROUND: To evaluate the clinical outcome of patients with relapsed or
      refractory follicular lymphoma treated with immunochemotherapy, in vivo purging
      and high-dose therapy with autotransplant. PATIENTS AND METHODS: Sixty-four
      patients were enrolled in the trial. Primary end point was progression-free
      survival (PFS). Secondary end points were the in vivo purging effect on stem-cell
      harvest and the impact of molecular response on the outcome. RESULTS: At
      enrollment, 59% of patients were PCR+ for bcl-2 rearrangement in bone marrow (PCR
      informative). After the immunochemotherapy, before mobilization, 97% obtained
      complete response or partial response and 87% of patients informative for bcl-2
      were molecularly negative. Sixty-one patients proceeded to in vivo purging and
      peripheral blood stem cell (PBSC) mobilization with rituximab and high-dose AraC.
      The median number of CD34+ cells collected was 16.6 x 10(6)/kg. Of 33 PCR
      informative patients, the harvests resulted in PCR- in all. Fifty-eight patients
      received high-dose therapy and autotransplant of in vivo purged PBSC. After a
      median follow-up of 3.5 years, 41 patients are in complete remission. Five-year
      PFS is 59%. CONCLUSION: This study demonstrates that patients with advanced
      relapsed or refractory follicular lymphoma treated with immunochemotherapy, in
      vivo purging and autotransplant may obtain long-lasting PFS. In bcl-2-positive
      patients, in vivo purging allows the harvest of lymphoma-free PBSC. Absence of
      the bcl-2 rearrangement after autotransplant is associated with persistent
      clinical remission.

PMID- 18344537
TI  - Concurrent trastuzumab with adjuvant radiotherapy in HER2-positive breast cancer
      patients: acute toxicity analyses from the French multicentric study.
AB  - BACKGROUND: Trastuzumab (T) combined with chemotherapy has been recently shown to
      improve outcome in HER2-positive breast cancer (BC). The aim of this study was to
      evaluate the toxic effects of concurrent radiation therapy (RT) and T
      administration in the adjuvant setting. PATIENTS AND METHODS: Data of 146
      patients with stages II-III HER2-positive BC were recorded. Median age was 46
      years. In all, 32 (23%) and 114 (77%) patients received a weekly and a 3-week T
      schedule, respectively. A median dose of 50 Gy was delivered after surgery.
      Internal mammary chain (IMC) was irradiated in 103 (71%) patients. RESULTS: Grade
      >2 dermatitis and esophagitis were noted in 51% and 12%, respectively. According
      to the Common Toxicity Criteria v3.0 scale and HERA (HERceptin Adjuvant) trial
      criteria, respectively, 10% and 6% of the patients had a grade >/=2 of left
      ventricular ejection fraction (LVEF) decrease after RT. Multivariate analyses
      revealed two independent prognostic factors: weekly T administration (for LVEF
      decrease) and menopausal status (for dermatitis). Higher level of T cumulative
      dose (>1600 mg) was only borderline of statistical significance for acute
      esophagitis toxicity. CONCLUSION: We showed that weekly concurrent T and RT are
      feasible in daily clinical practice with, however, a decrease of LVEF. Cardiac
      volume sparing and patient selections for IMC irradiation are highly recommended.
      Longer follow-up is warranted to evaluate late toxic effects.

PMID- 18344538
TI  - Family mediation of mathematically based concepts while engaged in a problem
      solving activity with their young deaf children.
AB  - This qualitative study examined the relationship between young deaf children's
      level of mathematics ability ("high" and "low," as defined by test score on the
      Test of Early Mathematics Ability-3) and opportunities available for the
      construction of early mathematics knowledge during a problem-solving task
      implemented by their parents. Findings indicate that the manner in which the
      mathematically based concepts (number/counting, quantity, time/sequence, and
      categorization) were incorporated into the activity was more meaningful for
      children who demonstrated high levels of mathematical ability. In addition,
      children who demonstrated high levels of mathematical ability experienced a more
      purposeful use of mediation during activity implementation; however, overall use
      of mediated learning experience was limited for children from both ability
      groups.

PMID- 18344539
TI  - Academic status of deaf and hard-of-hearing students in public schools: student,
      home, and service facilitators and detractors.
AB  - We examined facilitators and detractors of academic success of 25 deaf or hard-of
      hearing (DHH) students selected from a pool of 187 students attending general
      education classes and enrolled in a study of academic progress. Interviews with
      their teachers of DHH, general education teachers, principals, parents,
      interpreters, and students themselves were analyzed for child, family, and school
      facilitators and detractors of academic status. Facilitators included student
      self-advocacy and motivation, high family and school expectations, families'
      ability to help with homework, and good communication between professionals.
      Detractors included additional disabilities and poor family-school communication.
      A comparison of above- and below-average students revealed no single
      distinguishing facilitator or detractor. Each above-average student had many
      facilitators, whereas each below-average student had several significant
      detractors.

PMID- 18344540
TI  - SUMO assay with peptide arrays on solid support: insights into SUMO target sites.
AB  - The modification of proteins by SUMO (small ubiquitin-like modifier) regulates
      various cellular processes. Sumoylation often occurs on a specific lysine residue
      within the consensus motif psiKxE/D. However, little is known about the
      specificity and selectivity of SUMO target sites. We describe here a SUMO assay
      with peptide array on solid support for the simultaneous characterization of
      hundreds of different SUMO target sites. This approach was used to characterize
      known SUMO substrates. The position of the motif within the peptide and the amino
      acids flanking the acceptor site affected the efficiency of SUMO modification.
      Interestingly, a sequence of only four amino acids, corresponding to the SUMO
      consensus motif without flanking amino acids, was a bona fide target site.
      Analysis of a peptide library for all variants of the psiKxE/D consensus motif
      revealed that the first and third positions in the tetrapeptide preferably
      contain aromatic amino acid residues. Furthermore, by adding the SUMO E3 ligase
      PIAS1 to the reaction mixture, we show specific enhancement of the modification
      of a PIAS1-dependent SUMO substrate in this system. Overall, our results
      demonstrate that the sumoylation assay with peptide array on solid support can be
      used for the high-throughput characterization of SUMO target sites, and provide
      new insights into the composition, selectivity and specificity of SUMO target
      sites.

PMID- 18344541
TI  - One-step purification of lectins from banana pulp using sugar-immobilized gold
      nano-particles.
AB  - To obtain lectins without tedious purification steps, we developed a convenient
      method for a one-step purification of lectins using sugar-immobilized gold nano
      particles (SGNPs). Proteins in crude extracts from plant materials were
      precipitated with 60% ammonium sulphate, and the precipitate was re-dissolved in
      a small volume of phosphate buffer. The resultant solution was then mixed with
      appropriate SGNPs under an optimized condition. After incubating overnight at 4
      degrees C, lectins in the mixture formed aggregate with SGNPs, which was visually
      detected and easily sedimented by centrifugation. The aggregate was dissolved by
      adding inhibitory sugars, which were identical to the non-reducing sugar moieties
      on the SGNPs. According to SDS-PAGE and MS of thus obtained proteins, it was
      found that SGNPs isolated lectins with a high purity. For example, a protein
      isolated from banana using Glcalpha-GNP (alpha-glucose-immobilized gold nano
      particle) was identified as banana lectin by trypsin-digested peptide-MS finger
      printing method.

PMID- 18344542
TI  - Chemical modulation of the chaperone function of human alphaA-crystallin.
AB  - alphaA-crystallin is abundant in the lens of the eye and acts as a molecular
      chaperone by preventing aggregation of denaturing proteins. We previously found
      that chemical modification of the guanidino group of selected arginine residues
      by a metabolic alpha-dicarbonyl compound, methylglyoxal (MGO), makes human alphaA
      crystallin a better chaperone. Here, we examined how the introduction of
      additional guanidino groups and modification by MGO influence the structure and
      chaperone function of alphaA-crystallin. alphaA-crystallin lysine residues were
      converted to homoarginine by guanidination with o-methylisourea (OMIU) and then
      modified with MGO. LC-ESI-mass spectrometry identified homoargpyrimidine and
      homohydroimidazolone adducts after OMIU and MGO treatment. Treatment with 0.25 M
      OMIU abolished most of the chaperone function. However, subsequent treatment with
      1.0 mM MGO not only restored the chaperone function but increased it by
      approximately 40% and approximately 60% beyond that of unmodified alphaA
      crystallin, as measured with citrate synthase and insulin aggregation assays,
      respectively. OMIU treatment reduced the surface hydrophobicity but after MGO
      treatment, it was approximately 39% higher than control. FRET analysis revealed
      that alphaA-crystallin subunit exchange rate was markedly retarded by OMIU
      modification, but was enhanced after MGO modification. These results indicate a
      pattern of loss and gain of chaperone function within the same protein that is
      associated with introduction of guanidino groups and their neutralization. These
      findings support our hypothesis that positively charged guanidino group on
      arginine residues keeps the chaperone function of alphaA-crystallin in check and
      that a metabolic alpha-dicarbonyl compound neutralizes this charge to restore and
      enhance chaperone function.

PMID- 18344543
TI  - Bromophenol blue binding as a probe to study urea and guanidine hydrochloride
      denaturation of bovine serum albumin.
AB  - Urea and guanidine hydrochloride (GdnHCl) denaturation of bovine serum albumin
      (BSA) were investigated using bromophenol blue (BPB) binding as a probe. Addition
      of BPB to BSA produced an absorption difference spectrum in the wavelength range,
      525-675 nm with a minimum at 587 nm and a maximum at 619 nm. The magnitude of
      absorption difference (DeltaAbs.) at 619 nm decreased on increasing urea/GdnHCl
      concentration and followed the denaturation curve. The denaturation was found to
      be a two-state, single-step transition. The transitions started at 1.75 and 0.875
      M and completed at 6.5 and 3.25 M with the mid point occurring around 4.0 and 1.5
      M urea and GdnHCl concentrations, respectively. The value of free energy of
      stabilization, DeltaGDH2O as determined from urea and GdnHCl denaturation curves
      was found to be 4041 and 4602 cal/mol, respectively. Taken together, these
      results suggest that BPB binding can be used as a probe to study urea and GdnHCl
      denaturation of BSA.

PMID- 18344544
TI  - Pfam 10 years on: 10,000 families and still growing.
AB  - Classifications of proteins into groups of related sequences are in some respects
      like a periodic table for biology, allowing us to understand the underlying
      molecular biology of any organism. Pfam is a large collection of protein domains
      and families. Its scientific goal is to provide a complete and accurate
      classification of protein families and domains. The next release of the database
      will contain over 10,000 entries, which leads us to reflect on how far we are
      from completing this work. Currently Pfam matches 72% of known protein sequences,
      but for proteins with known structure Pfam matches 95%, which we believe
      represents the likely upper bound. Based on our analysis a further 28,000
      families would be required to achieve this level of coverage for the current
      sequence database. We also show that as more sequences are added to the sequence
      databases the fraction of sequences that Pfam matches is reduced, suggesting that
      continued addition of new families is essential to maintain its relevance.

PMID- 18344545
TI  - Anti-herbivore structures of Paulownia tomentosa: morphology, distribution,
      chemical constituents and changes during shoot and leaf development.
AB  - BACKGROUND AND AIMS: Recent studies have shown that small structures on plant
      surfaces serve ecological functions such as resistance against herbivores. The
      morphology, distribution, chemical composition and changes during shoot and leaf
      development of such small structures were examined on Paulownia tomentosa.
      METHODS: The morphology and distribution of the structures were studied under
      light microscopy, and their chemical composition was analysed using thin-layer
      chromatography and high-performance liquid chromatography. To further investigate
      the function of these structures, several simple field experiments and
      observations were also conducted. KEY RESULTS: Three types of small structures on
      P. tomentosa were investigated: bowl-shaped organs, glandular hairs and dendritic
      trichomes. The bowl-shaped organs were densely aggregated on the leaves near
      flower buds and were determined to be extrafloral nectarines (EFNs) that secrete
      sugar and attract ants. Nectar production of these organs was increased by
      artificial damage to the leaves, suggesting an anti-herbivore function through
      symbiosis with ants. Glandular hairs were found on the surfaces of young and/or
      reproductive organs. Glandular hairs on leaves, stems and flowers secreted
      mucilage containing glycerides and trapped small insects. Secretions from
      glandular hairs on flowers and immature fruits contained flavonoids, which may
      provide protection against some herbivores. Yellow dendritic trichomes on the
      adaxial side of leaves also contained flavonoids identical to those secreted by
      the glandular hairs on fruits and flowers. Three special types of leaves, which
      differed from the standard leaves in shape, size and identity of small
      structures, developed near young shoot tips or young flower buds. The density of
      small structures on these leaf types was higher than on standard leaves,
      suggesting that these leaf types may be specialized to protect young leaves or
      reproductive organs. Changes in the small structures during leaf development
      suggested that leaves of P. tomentosa are primarily protected by glandular hairs
      and dendritic trichomes at young stages and by the EFNs at mature stages.
      CONCLUSIONS: The results indicate that P. tomentosa protects young and/or
      reproductive organs from herbivores through the distribution and allocation of
      small structures, the nature of which depends on the developmental stage of
      leaves and shoots.

PMID- 18344546
TI  - Epidemiology of rotavirus infection in north-western Nigeria.
AB  - Rotaviruses (RV) are associated with approximately 33 000 deaths in children <5
      years of age annually in Nigeria. However, limited data exit on RV infection in
      north-western Nigeria. During July 2002 to July 2004, 1063 (869 diarrhoeic and
      194 control) stool samples were collected from children <5 years of age
      presenting with diarrhoea in north-western Nigeria. The stools were analysed for
      RV antigen and further characterized by antigenic and genomic methods. RV was
      detected in 18% of children with diarrhoea and 7.2% of the age-matched case
      controls. The highest RV burden was detected in children <6-months-old. Long
      electropherotypes and VP6 subgroup I + II specificity predominated.

PMID- 18344547
TI  - Daptomycin resistance in Enterococcus faecalis prosthetic valve endocarditis.

PMID- 18344548
TI  - Gram-negative bacteraemia in non-ICU patients: factors associated with inadequate
      antibiotic therapy and impact on outcomes.
AB  - BACKGROUND: A considerable number of gram-negative bacteraemias occur outside
      intensive care units (ICUs). Inadequate antibiotic therapy in ICUs has been
      associated with adverse outcomes; however, there are no prospective studies in
      non-ICU patients. METHODS: A 6 month (1 August 2006-31 January 2007), prospective
      cohort study of non-ICU patients with gram-negative bacteraemia in a tertiary
      care hospital was performed. Inadequate empirical antibiotic therapy was defined
      as no antibiotic or starting a non-susceptible antibiotic within 24 h after the
      initial positive blood culture. RESULTS: Two hundred and fifty non-ICU patients
      had gram-negative bacteraemia. The mean age was 56.4 (+/-16.1) years. The
      predominant bacteria in monomicrobial infections were Escherichia coli (24%),
      Klebsiella pneumoniae (18%) and Pseudomonas aeruginosa (8%). Sixty-one (24%)
      patients had polymicrobial bacteraemia. Seventy patients (28%) required ICU
      transfer and 35 (14%) died. Seventy-nine (31.6%) received inadequate empirical
      antibiotic therapy. These patients were more likely to have a hospital-acquired
      infection [odds ratio (OR) = 1.99, 95% confidence interval (CI) = 1.11-3.56, P =
      0.02] and less likely to have E. coli monomicrobial bacteraemia [OR 0.40 (95% CI
      0.19-0.86), P = 0.02]. There were no differences in occurrence of sepsis [72
      (91.1%) patients with inadequate versus 159 (93.0%) with adequate therapy; P =
      0.6], ICU transfer [20 (25.3%) versus 50 (29.2%); P = 0.5], post-bacteraemia
      length of stay (median = 6.8 versus 6.1 days; P = 0.09) or death [11 (13.9%)
      versus 24 (14.0%); P = 1.0]. CONCLUSIONS: Nearly one-third of the non-ICU
      patients with gram-negative bacteraemia received inadequate empirical antibiotic
      therapy. There was no difference in adverse outcomes between patients receiving
      inadequate or adequate therapy in this study.

PMID- 18344549
TI  - Disposition of valganciclovir during continuous renal replacement therapy in two
      lung transplant recipients.
AB  - OBJECTIVES: To determine whether valganciclovir 450 mg every 48 h for
      cytomegalovirus (CMV) prophylaxis provides appropriate ganciclovir exposure in
      solid organ transplant recipients during continuous renal replacement therapy
      (CRRT). PATIENTS AND METHODS: Ganciclovir pharmacokinetics was intensively
      studied in two lung transplant recipients under valganciclovir 450 mg every 48 h
      over one dosing interval. In vitro experiments using blank whole blood spiked
      with ganciclovir further investigated exchanges between plasma and erythrocytes.
      RESULTS: Ganciclovir disposition was characterized by apparent total body
      clearance of 3.3 and 5.8 L/h, terminal half-life of 16.9 and 14.1 h, and apparent
      volume of distribution of 60.3 and 104.9 L in Patients 1 and 2, respectively. The
      observed sieving coefficient was 1.05 and 0.96, and the haemofiltration clearance
      was 3.3 and 3.1 L/h. In vitro experiments confirmed rapid efflux of ganciclovir
      from red blood cells into plasma, increasing the apparent efficacy of
      haemofiltration. CONCLUSIONS: A valganciclovir dosage of 450 mg every 48 h
      appears adequate for patients under CRRT requiring prophylaxis for CMV infection,
      providing concentration levels in the range reported for 900 mg once daily dosing
      outside renal failure.

PMID- 18344550
TI  - HIV-1 drug resistance genotyping from dried blood spots stored for 1 year at 4
      degrees C.
AB  - BACKGROUND: Dried blood spots (DBSs) are an attractive alternative to plasma for
      HIV-1 drug resistance testing in resource-limited settings. We recently showed
      that HIV-1 can be efficiently genotyped from DBSs stored at -20 degrees C for
      prolonged periods (0.5-4 years). Here, we evaluated the efficiency of genotyping
      from DBSs stored at 4 degrees C for 1 year. METHODS: A total of 40 DBSs were
      prepared from residual diagnostic specimens collected from HIV subtype B-infected
      persons and were stored with desiccant at 4 degrees C. Total nucleic acids were
      extracted after 1 year using a modification of the Nuclisens assay. Resistance
      testing was performed using the ViroSeq HIV-1 assay and an in-house nested RT-PCR
      method validated for HIV-1 subtype B that amplifies a smaller (1 kb) pol
      fragment. RESULTS: Using the ViroSeq assay, only 23 of the 40 (57.5%) DBS
      specimens were successfully genotyped; 22 of these specimens had plasma viraemia
      >10,000 RNA copies/mL. When the specimens were tested using the in-house assay,
      38 of the 40 DBSs (95%) were successfully genotyped. Overall, resistance
      genotypes generated from the DBSs and plasma were highly concordant. CONCLUSIONS:
      We show that drug resistance genotyping from DBSs stored at 4 degrees C with
      desiccant is highly efficient but requires the amplification of small pol
      fragments and the use of an in-house nested PCR protocol with quality-controlled
      reagents. These findings suggest that 4 degrees C may represent a suitable
      temperature for long-term storage of DBSs.

PMID- 18344551
TI  - Body radioactivity and radiation dose from 40K in Bangladeshi subjects measured
      with a whole-body counter.
AB  - A group of subjects of Bangladeshi adults from both sexes were studied for
      internal radioactivity and effective dose by measuring the whole-body activity of
      naturally occurring 40K using a whole-body counter. The mean activity
      concentration in the whole body and effective dose due to naturally occurring 40K
      for the average male were found to be 2.0 +/- 0.4 Bq x g(-1) and 100 +/- 26
      microSv x y(-1), respectively and those for the average female were 1.7 +/- 0.3
      Bq x g(-1) and 100 +/- 20 microSv x y(-1), respectively. The mean activity
      concentration in the whole body and effective dose for both sexes were 1.9 +/-
      0.4 Bq x g(-1) and 100 +/- 25 microSv x y(-1), respectively. The effective dose
      from 40K for subjects is below the value reported by the UNSCEAR.

PMID- 18344552
TI  - Analgesic effectiveness of caudal levobupivacaine and ketamine.
AB  - BACKGROUND: Ketamine is used increasingly in paediatric anaesthetic practice to
      prolong the action of a caudal block. This study was designed to determine if
      adding S(+)-ketamine 0.5 mg kg(-1) allows a lower concentration of
      levobupivacaine to be used for caudal anaesthesia without loss of clinical
      effectiveness. METHODS: One hundred and sixty-four children (ASA I or II) aged 3
      months-6 yr were randomly allocated to receive 1 ml kg(-1) of levobupivacaine
      0.15% with 0.5 mg kg(-1) S(+)-ketamine (Group 1), levobupivacaine 0.175% with 0.5
      mg kg(-1) S(+)-ketamine (Group 2), or levobupivacaine 0.2% (Group 3) by the
      caudal route. Pain, motor block, sedation, and requirement for postoperative
      analgesia were assessed up to 6 h after operation. RESULTS: There was no
      significant difference between the groups in effectiveness at first surgical
      incision. Significantly lower analgesic requirements were reported in Group 2
      compared with Group 3 at wakeup, 180 and 360 min after operation. Time to first
      rescue analgesia was longer in Group 2 compared with Group 1 or 3. Kaplan-Meier
      survival analysis of analgesia free time demonstrated a significant advantage of
      Group 2 over Groups 1 and 3 (log rank P=0.05). The incidence of postoperative
      motor block was not significantly different between the groups. No excess
      sedation or dysphoric reactions were observed in the ketamine groups.
      CONCLUSIONS: The addition of 0.5 mg kg(-1) S(+)-ketamine to levobupivacaine
      0.175% for caudal analgesia for lower abdominal and urological surgery is
      significantly more effective in providing postoperative analgesia than
      levobupivacaine 0.15% with 0.5 mg kg(-1) S(+)-ketamine or levobupivacaine 0.2%.

PMID- 18344553
TI  - Positron emission tomography study of regional cerebral blood flow and flow
      metabolism coupling during general anaesthesia with xenon in humans.
AB  - BACKGROUND: The effects of xenon on regional cerebral blood flow (rCBF) are
      controversial. Moreover, the precise sites of action at which xenon exerts its
      effects in the human brain remain to be established. METHODS: rCBF was
      sequentially assessed by H(2)(15)O positron emission tomography in six
      volunteers. rCBF was determined at baseline and during general anaesthesia
      induced with propofol and maintained with one minimum alveolar concentration
      xenon. rCBF measurements were started after the calculated plasma concentration
      of propofol had decreased to subanaesthetic levels (<1.0 microg ml(-1)). Changes
      in rCBF were calculated for 13 cerebral volumes of interest by measurement of a
      semi-quantitative perfusion index (PI). In addition, voxel-wise changes in rCBF
      were analysed using statistical parametric mapping. RESULTS: Xenon had only minor
      effects on PI in grey matter volumes of interest. In contrast, PI was increased
      in white matter [from 1.01 (0.11) to 1.24 (0.15) kcnt ml(-1) MBq(-1), P=0.05,
      mean (SD)]. Voxel-based analysis showed an increase of rCBF in white matter and a
      relative decrease of rCBF during xenon anaesthesia in distinct grey matter
      regions, particularly the orbito- and mesiofrontal cortex, cingulate gyrus,
      thalamus, hippocampus and bilateral cerebellum (P<0.05 corrected). When
      correlating PI with cerebral metabolic rate of glucose (previously obtained in
      another group of six volunteers using (18)F-fluorodeoxyglucose as tracer), the
      flow-metabolism coupling was preserved during xenon anaesthesia. CONCLUSIONS:
      Xenon exerted distinct regional effects on CBF: relative decreases in several
      cortical, subcortical, and cerebellar areas were accompanied by an increase in
      white matter. Flow-metabolism coupling was not impaired during xenon anaesthesia.

PMID- 18344554
TI  - Laparoscopic cholecystectomy in a patient with an implantable left ventricular
      assist device.
AB  - Left ventricular assist devices (LVADs) provide mechanical support for left
      ventricular ejection in the failing heart. We describe the anaesthetic management
      of a patient with an LVAD requiring laparoscopic cholecystectomy. A 51-yr-old
      female patient with severe heart disease had a Heartmate II LVAD implanted 4
      months before this proposed elective surgery. Maintaining haemodynamic stability
      in the perioperative period is essential in such patients. The case was managed
      successfully using invasive monitoring and anaesthesia with sevoflurane and
      remifentanil. The potential problems in management of patients with LVADs are
      highlighted and discussed. A team approach is essential.

PMID- 18344555
TI  - Modulation of AMPA receptor GluR1 subunit phosphorylation in neurons by the
      intravenous anaesthetic propofol.
AB  - BACKGROUND: The ionotropic glutamate receptor is a potential molecular site in
      the central nervous system that general anaesthetics may interact with to produce
      some of their biological actions. Protein phosphorylation has been well
      documented to occur in the intracellular C-terminal domain of alpha-amino-3
      hydroxy-5-methylisoxazole-4-propionic acid (AMPA) subtype of glutamate receptors,
      which represents a pivotal mechanism for the post-translational modulation of
      AMPA receptor functions. In this study, we investigated a possible influence of
      an i.v. anaesthetic agent propofol on the phosphorylation of AMPA receptor GluR1
      subunits in cultured neurons. METHODS: The effect of propofol on phosphorylation
      of GluR1 subunits at serine 831 and 845 was assayed in cultured rat striatal and
      cortical neurons by western blot with phospho- and site-specific antibodies.
      RESULTS: Propofol consistently elevated phosphorylation of GluR1 subunits at the
      C-terminal serine 845 site in both striatal and cortical neurons. The elevation
      in phosphorylation was concentration-dependent and started at a low concentration
      (3 microM). This increase in serine 845 phosphorylation was rapid and sustained
      during the entire course of propofol exposure. In contrast to serine 845,
      phosphorylation of GluR1 at serine 831 was not altered by propofol in striatal
      and cortical neurons. Total GluR1 abundance remained unchanged in response to
      propofol incubation. CONCLUSIONS: These data indicate that propofol possesses the
      ability to upregulate AMPA receptor GluR1 subunit phosphorylation at a specific
      serine 845 site in neurons and provide evidence supporting the AMPA receptor as a
      molecular target for general anaesthetics.

PMID- 18344556
TI  - Xenon or propofol anaesthesia for patients at cardiovascular risk in non-cardiac
      surgery.
AB  - BACKGROUND: The results of two European multi-centre trials on xenon anaesthesia
      led to the hypothesis that a xenon-based anaesthetic would keep left ventricular
      (LV) and circulatory function more stable than a propofol-based anaesthetic, in
      patients with coronary artery disease (CAD). METHODS: In a prospective,
      randomized design, 40 patients of ASA classes III and IV with known CAD were
      anaesthetized for elective non-cardiac surgery with either xenon (n=20) or
      propofol (n=20), each combined with remifentanil. Target criteria were
      intraoperative LV function as evaluated by transoesophageal echocardiography
      (TOE: Tei index, circumferential fibre shortening), arterial pressure, and heart
      rate (HR). RESULTS: Mean arterial pressure was decreased with propofol but was
      stable at pre-anaesthetic level with xenon (P<0.02) and HR was lower with xenon
      (P<0.01). The Tei index (also known as myocardial performance index) improved
      from 0.53 (0.14) to 0.45 (0.10) after 1 h with xenon and changed from 0.50 (0.14)
      to 0.55 (0.20) with propofol anaesthesia [means (SD); P=0.01 between the groups].
      Deviation of circumferential fibre shortening from expected value after 1 h was 
      2 (14)% with xenon and -14 (18)% with propofol [means (SD); P=0.03]. There were
      no perioperative signs of acute myocardial ischaemia (TOE, ECG, and troponin T
      release). CONCLUSIONS: Xenon anaesthesia provided a higher arterial pressure
      level than propofol, with no signs of cardiovascular compromise, in patients with
      CAD. Echocardiographic indices showed better LV function with xenon.

PMID- 18344557
TI  - A mouse model of human mucopolysaccharidosis IX exhibits osteoarthritis.
AB  - Hyaluronidases are endoglycosidases that hydrolyze hyaluronan (HA), an abundant
      component of the extracellular matrix of vertebrate connective tissues. Six human
      hyaluronidase-related genes have been identified to date. Mutations in one of
      these genes cause a deficiency of hyaluronidase 1 (HYAL1) resulting in a
      lysosomal storage disorder, mucopolysaccharidosis (MPS) IX. We have characterized
      a mouse model of MPS IX and compared its phenotype with the human disease. The
      targeted Hyal1 allele in this model had a neomycin resistance cassette in exon 2
      that replaced 753 bp of the coding region containing the predicted enzyme active
      site. As a result, Hyal1(-/-) animals had no detectable wild-type Hyal1
      transcript, protein or serum activity. Hyal1 null animals were viable, fertile
      and showed no gross abnormalities at 1 year and 8 months of age. Histological
      studies of the knee joint showed a loss of proteoglycans occurring as early as 3
      months that progressed with age. An increased number of chondrocytes displaying
      intense pericellular and/or cytoplasmic HA staining were detected in the
      epiphyseal and articular cartilage of null mice, demonstrating an accumulation of
      HA. Elevations of HA were not detected in the serum or non-skeletal tissues,
      indicating that osteoarthritis is the key disease feature in a Hyal1 deficiency.
      Hyal3 expression was elevated in Hyal1 null mice, suggesting that Hyal3 may
      compensate in HA degradation in non-skeletal tissues. Overall, the murine MPS IX
      model displays the key features of the human disease.

PMID- 18344558
TI  - Identification of a novel asthma susceptibility gene on chromosome 1qter and its
      functional evaluation.
AB  - Asthma is a multifactorial disease, in which the intricate interplay between
      genetic and environmental factors underlies the overall phenotype of the disease.
      Using a genome-wide scan for linkage in a population comprising of Danish
      families, we identified a novel linked locus on chromosome 1qter (LOD 3.6,
      asthma) and supporting evidence for this locus was identified for both asthma and
      atopic-asthma phenotypes in the GAIN (Genetics of Asthma International Network)
      families. The putative susceptibility gene was progressively localized to a 4.5
      Mb region on chromosome 1q adjacent to the telomere, through a series of
      genotyping screens. Further screening using the pedigree-based association test
      (PBAT) identified polymorphisms in the OPN3 and CHML genes as being associated
      with asthma and atopic asthma after correcting for multiple comparisons. We
      observed that polymorphisms flanking the OPN3 and CHML genes wholly accounted for
      the original linkage in the Danish population and the genetic association was
      also confirmed in two separate studies involving the GAIN families. OPN3 and CHML
      are unique genes with no known function that are related to the pathophysiology
      of asthma. Significantly, analysis of gene expression at both RNA and protein
      levels, clearly demonstrated OPN3 expression in lung bronchial epithelia as well
      as immune cells, while CHML expression appeared minimal. Moreover, OPN3 down
      regulation by siRNA knock-down in Jurkat cells suggested a possible role for OPN3
      in modulation of T-cell responses. Collectively, these data suggest that OPN3 is
      an asthma susceptibility gene on 1qter, which unexpectedly may play a role in
      immune modulation.

PMID- 18344559
TI  - Changes in sensory-evoked synaptic activation of motoneurons after spinal cord
      injury in man.
AB  - Following spinal cord injury (SCI), prolonged muscle spasms are readily triggered
      by brief sensory stimuli. Animal and indirect human studies have shown that a
      substantial portion of the depolarization of motoneurons during a muscle spasm
      comes from the activation of persistent inward currents (PICs). The brief (single
      pulse) sensory stimuli that trigger the PICs and muscle spasms in chronically
      spinalized animals evoke excitatory post-synaptic potentials (EPSPs) that are
      broadened to more than 500 ms, the duration of depolarization required to
      activate a PIC in the motoneuron. Thus, in humans, we investigated if post
      synaptic potentials (PSPs) evoked from brief (<20 ms) sensory stimulation are
      changed after SCI and if they are broadened to > or =500 ms to more readily
      activate motoneuron PICs and muscle spasms. To estimate both the shape and
      duration of PSPs in human subjects we used peristimulus frequencygrams (PSFs),
      which are plots of the instantaneous firing frequency of tonically active single
      motor units that are time-locked to the occurrence of the sensory stimulus. PSFs
      in response to cutaneomuscular stimulation of the medial arch or toe of the foot,
      a sensory stimulus that readily triggers muscle spasms, were compared between non
      injured control subjects and in spastic subjects with chronic (>1 year),
      incomplete SCI. In non-injured controls, a single shock or brief (<20 ms) train
      of cutaneomuscular stimulation produced PSFs consisting of a 300 ms increase in
      firing rate above baseline with an interposed period of reduced firing. Parallel
      intracellular experiments in motoneurons of adult rats revealed that a 300 ms
      EPSP with a fast intervening inhibitory PSP (IPSP) reproduced the PSF recorded in
      non-injured subjects. In contrast, the same brief sensory stimulation in subjects
      with chronic SCI produced PSFs of comparatively long duration (1200 ms) with no
      evidence for IPSP activation, as reflected by a lack of reduced firing rates
      after the onset of the PSF. Thus, unlike non-injured controls, the motoneurons of
      subjects with chronic SCI are activated by very long periods of pure
      depolarization from brief sensory activation. It is likely that these second-long
      EPSPs securely recruit slowly activating PICs in motoneurons that are known to
      mediate, in large part, the many seconds-long activation of motoneurons during
      involuntary muscle spasms.

PMID- 18344560
TI  - Disconnecting force from money: effects of basal ganglia damage on incentive
      motivation.
AB  - Bilateral basal ganglia lesions have been reported to induce a particular form of
      apathy, termed auto-activation deficit (AAD), principally defined as a loss of
      self-driven behaviour that is reversible with external stimulation. We
      hypothesized that AAD reflects a dysfunction of incentive motivation, a process
      that translates an expected reward (or goal) into behavioural activation. To
      investigate this hypothesis, we designed a behavioural paradigm contrasting an
      instructed (externally driven) task, in which subjects have to produce different
      levels of force by squeezing a hand grip, to an incentive (self-driven) task, in
      which subjects can win, depending on their hand grip force, different amounts of
      money. Skin conductance was simultaneously measured to index affective evaluation
      of monetary incentives. Thirteen AAD patients with bilateral striato-pallidal
      lesions were compared to thirteen unmedicated patients with Parkinson's; disease
      (PD), which is characterized by striatal dopamine depletion and regularly
      associated with apathy. AAD patients did not differ from PD patients in terms of
      grip force response to external instructions or skin conductance response to
      monetary incentives. However, unlike PD patients, they failed to distinguish
      between monetary incentives in their grip force. We conclude that bilateral
      striato-pallidal damage specifically disconnects motor output from affective
      evaluation of potential rewards.

PMID- 18344561
TI  - The human ventromedial frontal lobe is critical for learning from negative
      feedback.
AB  - Are positive and negative feedback weighed in a common balance in the brain, or
      do they influence behaviour through distinct neural mechanisms? Recent
      neuroeconomic studies in both human and non-human primates indicate that the
      ventromedial frontal lobe carries information about both losses and gains,
      suggesting that this region may encode value across the continuum from absolute
      negative to absolute positive outcomes. However, such work does not specify
      whether or how this value information is applied during behaviour. Observations
      of patients with ventromedial frontal damage indicate that this region is
      critical for certain forms of reinforcement learning and value-based decision
      making, but the underlying processes remain unclear. We disentangled the
      influence of cumulative positive and negative feedback on subsequent behaviour
      with a probabilistic reinforcement learning task in 11 patients with ventromedial
      frontal damage, 9 lesioned controls and 24 healthy controls, and found that
      ventromedial frontal damage selectively disrupted the ability to learn from
      negative feedback.

PMID- 18344562
TI  - Leadership, organization and health at work: a case study of a Swedish industrial
      company.
AB  - The application of knowledge on organization and leadership is important for the
      promotion of health at workplace. The purpose of this article is to analyse the
      leadership and organization, including the organizational culture, of a Swedish
      industrial company in relation to the health of the employees. The leadership in
      this company has been oriented towards developing and actively promoting a
      culture and a structure of organization where the employees have a high degree of
      control over their work situation. According to the employees, this means
      extensive possibilities for personal development and responsibility, as well as
      good companionship, which makes them feel well at work. This is also supported by
      the low sickness rate of the company. The results indicate that the leadership
      and organization of this company may have been conducive to the health of the
      employees interviewed. However, the culture of personal responsibility and the
      structure of self-managed teams seemed to suit only those who were able to manage
      the demands of the company and adapt to that kind of organization. Therefore, the
      findings indicate that the specific context of the technology, the environment
      and the professional level of the employees need to be taken into consideration
      when analysing the relation between leadership, organization and health at work.

PMID- 18344563
TI  - Searching for evidence of disease and malignant cell contamination in ovarian
      tissue stored from hematologic cancer patients.
AB  - BACKGROUND: Storing ovarian tissue for fertility preservation in cancer patients
      carries the risk of the presence of malignant cells that could lead to recurrence
      of cancer after reimplantation. Methods to exclude presence of cancer cells were
      used to improve the safety of cryopreservation-reimplantation procedures.
      METHODS: Fifty-eight patients with hematological malignancies were referred for
      the storage of ovarian tissue for fertility preservation. Investigation included
      preoperative imaging and histological evaluation of fresh ovarian tissue. After
      thawing markers to detect minimal residual disease (MRD) were used and compared
      with patient's disease used as positive control (five patients). RESULTS:
      Preoperative imaging detected disease in the ovaries (two patients). Conventional
      histology post-tissue harvesting did not disclose malignant cells (56 patients).
      MRD results post-thawing were negative in Hodgkin's disease (CD30
      immunohistochemical staining), in T- and B-cell lymphoma (PCR for T-cell receptor
      and Ig clones, respectively) and in two chronic myelogenous leukemia patients (RT
      PCR for BCR-ABL gene expression). However, highly sensitive real-time RT-PCR was
      positive in one CML patient and, this alarming result avoided tissue
      transplantation. CONCLUSIONS: Preoperative imaging prevented operations and
      storage of tissue with cancer. Evaluation of stored ovarian tissue for MRD using
      sensitive markers is essential to increase safety and to prevent reimplantation
      of tissue with malignant cells.

PMID- 18344564
TI  - Effects of olfactory stimuli on arm-reaching duration.
AB  - The aim of the present study was to investigate the effects of olfactory stimuli
      on visually guided reaching. In Experiment 1, participants reached toward and
      grasped either a small (almond/strawberry) or a large (apple/orange) visual
      target. Any 1 of 4 odors corresponding to the visual stimuli or odorless air was
      administered before movement initiation. Within the same block of trials,
      participants smelled 1) an odor associated with an object of a different size
      than the target, 2) an odor associated with an object of a size equal to that of
      the target, or 3) odorless air. Results indicated that reaching duration was
      longer for trials in which the odor "size" and the visual target did not match
      than when they matched. In Experiment 2, the same procedures were applied but the
      "no-odor" trials were administered in a separate block to the "odor" trials.
      Similar results as for Experiment 1 were found. However, in contrast to
      Experiment 1, the presence of an odor increased the level of alertness resulting
      in a shortening of reaching duration. We contend that olfactory stimuli have the
      capacity to elicit motor plans interfering with those programmed for a movement
      toward a visual stimulus.

PMID- 18344565
TI  - Boosting method for nonlinear transformation models with censored survival data.
AB  - We propose a general class of nonlinear transformation models for analyzing
      censored survival data, of which the nonlinear proportional hazards and
      proportional odds models are special cases. A cubic smoothing spline-based
      component-wise boosting algorithm is derived to estimate covariate effects
      nonparametrically using the gradient of the marginal likelihood, that is computed
      using importance sampling. The proposed method can be applied to survival data
      with high-dimensional covariates, including the case when the sample size is
      smaller than the number of predictors. Empirical performance of the proposed
      method is evaluated via simulations and analysis of a microarray survival data.

PMID- 18344566
TI  - Cysteine 62 of Bax is critical for its conformational activation and its
      proapoptotic activity in response to H2O2-induced apoptosis.
AB  - Bax is activated and translocated onto mitochondria to mediate cytochrome c
      release and apoptosis. The molecular mechanisms of Bax activation during
      apoptosis remain a subject of debate. We addressed the question of whether
      reactive oxygen species could directly activate Bax for its subsequent
      translocation and apoptosis. Using the SW480 human colon adenocarcinoma cell line
      stably expressing Bax fused to GFP, we showed that H2O2 induces Bax
      conformational change, mitochondrial translocation, and subsequent
      oligomerization at mitochondria. We found that H2O2-induced Bax activation is
      dependent on the conserved cysteine residue 62 of Bax. Mutation of cysteine 62,
      but not cysteine 126, to serine or alanine abolished its activation by H2O2 but
      not other death stimuli, both in SW480 and Bax-deficient HCT116 cells, whereas
      wild type Bax sensitizes these cells to apoptosis. Cysteines of Bax could
      chemically react with H2O2. Mutation of Bax BH3 domain in the presence of
      cysteine 62 also abolished Bax proapoptotic activity. We conclude that reactive
      oxygen species could be a direct signal for Bax activation by reacting with
      cysteine residues. Our results identify a critical role of cysteine 62 in
      oxidative stress-induced Bax activation and subsequent apoptosis.

PMID- 18344567
TI  - Functional characterization of Escherichia coli MsbA: interaction with
      nucleotides and substrates.
AB  - The Escherichia coli MsbA protein is a 65-kDa member of the ATP-binding cassette
      superfamily. It is thought to function as an ATP-dependent lipid translocase that
      transports lipid A from the inner to the outer leaflet of the cytoplasmic
      membrane. MsbA with high ATPase activity was isolated and found to be homodimeric
      in detergent solution. The protein ATPase activity was inhibited by vanadate and
      showed variable patterns of stimulation and inhibition by lipid A and other
      compounds. The intrinsic tryptophan fluorescence of the protein was
      characterized, and dynamic quenching using acrylamide showed that a
      conformational change took place on binding of lipid A. Fluorescence quenching
      was used to characterize the interactions of MsbA with nucleotides and various
      putative substrates, including lipids, lipid-like compounds, and drugs. MsbA had
      an apparent binding affinity for ATP of approximately 2 mm and also bound
      nonhydrolyzable ATP analogs and fluorescent ATP derivatives. The putative
      substrate lipid A interacted with the protein with an affinity of 6.4 microm.
      Drugs that are known to be substrates for ABC multidrug transporters also
      interacted with MsbA with affinities in the range 0.25-50 microm. This study
      represents the first use of fluorescence approaches to estimate MsbA binding
      affinities for nucleotides and putative transport substrates.

PMID- 18344569
TI  - Combating the eosinophil with anti-interleukin-5 therapy.

PMID- 18344568
TI  - Treatment of patients with the hypereosinophilic syndrome with mepolizumab.
AB  - BACKGROUND: The hypereosinophilic syndrome is a group of diseases characterized
      by persistent blood eosinophilia, defined as more than 1500 cells per microliter
      with end-organ involvement and no recognized secondary cause. Although most
      patients have a response to corticosteroids, side effects are common and can lead
      to considerable morbidity. METHODS: We conducted an international, randomized,
      double-blind, placebo-controlled trial evaluating the safety and efficacy of an
      anti-interleukin-5 monoclonal antibody, mepolizumab, in patients with the
      hypereosinophilic syndrome. Patients were negative for the FIP1L1-PDGFRA fusion
      gene and required prednisone monotherapy, 20 to 60 mg per day, to maintain a
      stable clinical status and a blood eosinophil count of less than 1000 per
      microliter. Patients received either intravenous mepolizumab or placebo while the
      prednisone dose was tapered. The primary end point was the reduction of the
      prednisone dose to 10 mg or less per day for 8 or more consecutive weeks.
      RESULTS: The primary end point was reached in 84% of patients in the mepolizumab
      group, as compared with 43% of patients in the placebo group (hazard ratio, 2.90;
      95% confidence interval [CI], 1.59 to 5.26; P<0.001) with no increase in clinical
      activity of the hypereosinophilic syndrome. A blood eosinophil count of less than
      600 per microliter for 8 or more consecutive weeks was achieved in 95% of
      patients receiving mepolizumab, as compared with 45% of patients receiving
      placebo (hazard ratio, 3.53; 95% CI, 1.94 to 6.45; P<0.001). Serious adverse
      events occurred in seven patients receiving mepolizumab (14 events, including one
      death; mean [+/-SD] duration of exposure, 6.7+/-1.9 months) and in five patients
      receiving placebo (7 events; mean duration of exposure, 4.3+/-2.6 months).
      CONCLUSIONS: Our study shows that treatment with mepolizumab, an agent designed
      to target eosinophils, can result in corticosteroid-sparing for patients negative
      for FIP1L1-PDGFRA who have the hypereosinophilic syndrome. (ClinicalTrials.gov
      number, NCT00086658 [ClinicalTrials.gov].).

PMID- 18344571
TI  - Hypolipidaemic effects of high-dose insulin therapy.

PMID- 18344572
TI  - Volume 100: clinical investigations: where next?

PMID- 18344573
TI  - Ultrasound-guided lumbar plexus block through the acoustic window of the lumbar
      ultrasound trident.
AB  - Lumbar plexus block (LPB) is frequently used in combination with an ipsilateral
      sacral plexus or sciatic nerve block for lower limb surgery. This is
      traditionally performed using surface anatomical landmarks, and the site for
      local anaesthetic injection is confirmed by observing quadriceps muscle
      contraction to peripheral nerve stimulation. In this report, we describe a
      technique of ultrasound-guided LPB that was successfully used, in conjunction
      with a sciatic nerve block, for anaesthesia during emergency lower limb surgery.
      The anatomy, sonographic features, technique of identifying the lumbar plexus,
      and the potential benefits of using this approach are discussed.

PMID- 18344574
TI  - Burdened by training not by anaesthesia.

PMID- 18344575
TI  - Intubating laryngeal mask as a ventilatory device.

PMID- 18344576
TI  - Saving mothers' lives.

PMID- 18344577
TI  - Successful delivery in a morbidly obese patient after failed intubation and
      regional technique.

PMID- 18344578
TI  - Tension enterothorax.

PMID- 18344579
TI  - Nasal tracheal intubation improves the success rate when the Airway Scope blade
      fails to reach the larynx.

PMID- 18344580
TI  - Emergency anaesthesia in central core disease.

PMID- 18344581
TI  - Ethanol-induced acute pulmonary hypertension and right ventricular dysfunction in
      pigs.

PMID- 18344582
TI  - Placement of enterogastric tubes.

PMID- 18344583
TI  - Introduction: women, health, and healing in early modern Europe.
AB  - Women played substantial roles in health and healing in medieval and early-modern
      Europe. They have been undercounted in studies that rely upon occupational
      labels, but when we look at caregiving and bodywork, we can see women providing a
      broad range of services. Although women often healed in domestic settings,
      neither female patients nor practitioners should be considered in isolation from
      larger market forces that shaped men's healing work.

PMID- 18344584
TI  - Women or healers? Household practices and the categories of health care in late
      medieval Iberia.
AB  - Assessments of medieval health care used to focus on practitioners holding some
      sort of occupational label, resulting in a meager representation of women. This
      article intends to illustrate how women's significant contribution to healthcare
      can be mapped out by looking at the domestic space that is largely left outside
      the histories of medieval medicine. First, it explores the language that names
      women's activities to maintain health and alleviate illness, showing how words
      identifying women's capacities to heal come from everyday actions and belong to
      the semantic domain of women and mothers. The caring meanings ascribed to the
      words women, mothers, midwives, and nurses in the Iberian mother tongues conflate
      and describe a continuum of practice whose origin is the household, from where it
      expands to the community. Second, it discusses the importance of women's ordinary
      domestic care within the theoretical frame of the six non-naturals, particularly
      feeding and nourishing, as well as presenting the household as an open and
      flexible space providing health care beyond the family. Third, by considering
      recipes as privileged evidence, it attempts to piece together a preliminary
      textual history of women's household knowledges that for centuries had been
      circumscribed to the domain of the oral. It identifies the written contexts where
      women's recipes appear through a long timespan, attesting changes in women's
      literate practices that give rise to new genres that illuminate a sphere
      previously opaque to the historical record.

PMID- 18344585
TI  - A view from the streets: women and medical work in Elizabethan London.
AB  - In Elizabethan London, women occupied a significant position in the city's
      medical marketplace, both as consumers of medical services and as practitioners.
      Though male medical authors of the period objected to the presence and practices
      of these women, a very different view of their medical work emerges if we shift
      our historical vantage point to the streets, houses, churches, and hospitals of
      the city. Using relatively underutilized sources such as parish records, probate
      records, lists of immigrants to London, hospital records, and individual
      manuscripts it is possible to draw a richer, more detailed portrait of how female
      health-care workers engaged with the business of health and healing. Women emerge
      from these records as active, prominent, and acknowledged participants in the
      delivery of services that promoted and preserved the health of many Londoners
      from cradle to grave. Hired by public institutions such as parishes and
      hospitals, as well as by private individuals, women were central figures in the
      delivery of nursing, medical, pharmaceutical, and surgical services throughout
      the city as part of organized systems of health care. Exploring how Londoners saw
      female practitioners, and how women played a recognized role within the city's
      range of health-care options, demonstrates that women were crucial to community
      health, and were also valued as such by their neighbors and patients.

PMID- 18344586
TI  - Blood and expertise: the trials of the female medical expert in the ancien-regime
      courtroom.
AB  - This article explores the obstacles faced by the female medical expert in the
      early modern courtroom through a close reading of three case studies: Marie
      Garnier, expert midwife tried for false testimony in 1665, and Angelique Perrotin
      and Barbe-Francoise D'Igard, accused of false accusation of rape and infant
      substitution, respectively, in the 1730s. The difficulties of determining the
      veracity of the corporeal signs of a crime were particularly acute with regard to
      the reproductive female body, which was perceived to be less reliable than its
      male counterpart. The ability of the female medical expert to accurately and
      truthfully interpret such signs was also questionable, and at times she seems to
      have been as much "on trial" as the bodies of those she examined.

PMID- 18344587
TI  - Duchess, heal thyself: Elisabeth of Rochlitz and the patient's perspective in
      early modern Germany.
AB  - This article uses the case of German noblewoman Elisabeth of Rochlitz as a window
      on sixteenth-century patient attitudes toward disease and the body. A widowed
      duchess of Saxony, Elisabeth spent the last twenty years of her life battling an
      increasingly serious string of illnesses. Despite her ready access to learned
      physicians and her friendly relationship with several of them, she used a wide
      variety of practitioners and frequently privileged lower-status healers when she
      perceived their methods to be more efficacious. She placed the greatest weight on
      remedies that would relieve the experienced symptoms of her illness, rather than
      more holistic methods such as doctors' regimens. This perception of disease as a
      set of symptoms led to a dispute about the meaning of signs in her final illness.

PMID- 18344588
TI  - Making medicines in the early modern household.
AB  - This article is a study of household medicine production and consumption through
      an examination of the papers of Elizabeth Freke (1641-1714) and a wider survey of
      around nine thousand medical recipes in printed and manuscript collections from
      seventeenth-century England. It investigates the sorts of medicines that may have
      been produced in early modern households and the production methods, ingredients,
      and equipment used. Focusing on three inventories of medicines compiled by Freke
      between 1710 and 1712 as well as her manuscript recipe collection and medical
      reading notes, I contend that she kept on hand a number of cure-alls and
      medicines for general weaknesses, while holding onto recipes for more-specific
      ailments; the recipes, in these cases, would be the "just-in-case" medicine
      cabinet. I also argue for a close relationship between commercial and domestic
      medicine, and present the idea that household practitioners purchased not only
      ingredients (both processed and unprocessed) and equipment, but also medical
      knowledge.

PMID- 18344589
TI  - The death of Isabella Della Volpe: four eyewitness accounts of a postmortem
      caesarean section in 1545.
AB  - This article provides a transcription and translation of four notarized
      declarations describing the events surrounding a postmortem caesarean section
      performed in 1545 in Vercelli, a small city in the Duchy of Savoy. After her
      death in the late stages of pregnancy, Isabella della Volpe's body was opened and
      her fetus excised by a local barber, aided by a surgeon and a midwife. The
      article argues that the postmortem caesarean section was a well-known and widely
      accepted procedure and that it might be motivated by financial and legal as well
      as religious concerns; not only was it important to baptize the child for its
      salvation, but the fate of the mother's dowry, as in this case, might depend on
      whether she died with or without living issue.

PMID- 18344592
TI  - Cyclooxygenase-2 induction by lysophosphatidylcholine in cultured rat vascular
      smooth muscle cells: involvement of the p38MAPK pathway.
AB  - Lysophosphatidylcholine (lysoPC) stimulates the release of prostaglandins (PGs)
      in various cells and tissues. Cyclooxygenase (COX)-2 has recently emerged as a
      key regulator of PG synthesis. We investigated whether lysoPC regulates COX-2
      expression in cultured rat vascular smooth muscle cells (VSMCs). LysoPC strongly
      increased the expression of COX-2 mRNA in a time- and dose-dependent manner. COX
      2 protein expression also was increased by lysoPC. The p38 mitogen-activated
      protein kinase (MAPK) inhibitor SB203580 significantly suppressed lysoPC-induced
      COX-2 mRNA and protein expression, but not a p42/44MAPK kinase (MEK-1) inhibitor,
      PD98059. LysoPC did not increased the transcription of the COX-2 gene, as assayed
      with a COX-2 promoter/luciferase chimeric plasmid and suppressed the decay of COX
      2 mRNA. SB203580 markedly enhanced the decay of COX-2 mRNA induced by lysoPC,
      implying that p38MAPK activated by lysoPC helps to regulate COX-2 by stabilizing
      its mRNA. The COX-2 specific inhibitor NS-398 attenuated lysoPC-stimulated DNA
      and protein synthesis as well as PGE(2) production by VSMCs. These results
      suggest that in rat VSMCs lysoPC regulates COX-2 expression and PG production and
      also modulates cell proliferation through p38MAPK-mediated signaling pathways.

PMID- 18344593
TI  - Possible involvement of put A gene in Helicobacter pylori colonization in the
      stomach and motility.
AB  - H. pylori is a gram-negative bacterium associated with gastric inflammation and
      peptic ulcer and considered a risk factor for gastric cancer in its natural
      habitat. However, the energy metabolism of H. pylori in the stomach remains to be
      clarified. H. pylori shows rather high respiratory activity with L-proline and
      significantly large amounts of L-proline are present in the gastric juice from H.
      pylori infected patients. We constructed a disrupted mutant of the put A gene,
      which encodes the proline utilization A (Put A) flavin-linked enzyme, in order to
      examine the role of put A in the gastric colonization of H. pylori. The put A
      disrupted mutant, DeltaputA, was constructed by inserting a chloramphenicol
      resistant gene into put A. DeltaputA did not show respiratory activity using L
      proline and could not incorporate L-proline into cells. DeltaputA also did not
      show motility in response to amino acids and did not display the swarming
      activity observed with the wild-type. DeltaputA had lost its ability to colonize
      the stomach of nude mice, an ability possessed by the wild-type. These findings
      indicate that put A may play an important role in H. pylori colonization on the
      gastric mucus layer.

PMID- 18344594
TI  - Significant association of interleukin 10 receptor mRNA levels with renal cell
      carcinoma metastasis.
AB  - Immunosuppressive cytokine, interleukin 10 (IL-10), is associated with
      progression of the renal cell carcinoma (RCC). However, the roles of its cell
      surface receptor, interleukin 10 receptor (IL-10R), remain elusive. We quantified
      IL-10R mRNA expression in paired tumor and non-tumor samples from the surgical
      specimens of 71 consecutive patients with RCC using a real-time reverse
      transcription polymerase chain reaction (RT-PCR). The absolute level of IL-10R
      mRNAs in tumor and non-tumor tissues did not correlate with the malignant and
      metastatic profiles. The relative yields of the PCR product from the tumor tissue
      to that from the corresponding non-tumor tissue (T/N) for the expression of IL
      10R mRNAs were calculated. A high T/N ratio of IL-10R correlated with poor
      differentiation (P < 0.001) and metastasis (P < 0.0001). By univariate analysis,
      a high T/N ratio of IL-10R predicted a shortened overall survival in all cases (P
      < 0.01). These findings suggest that IL-10R is associated with the progression of
      RCC.

PMID- 18344595
TI  - Effect of tea catechins on body fat accumulation in rats fed a normal diet.
AB  - Although it is known that tea catechins exert potent effects in obese subjects,
      there is scant information concerning these effects on body weight gain and body
      fat accumulation in the non-obese. We studied normal rats fed a normal diet and
      water containing either 0.1% or 0.5% tea catechins to examine the effects on body
      fat content and serum cholesterol levels, as well as evaluating whether the
      effect is related to bile acids, which in recent years have emerged as an inducer
      of energy expenditure. The administration of 0.5% catechins decreased the
      accumulation of body fat and the serum levels of cholesterol and bile acids.
      These results indicate that tea catechins modulate lipid metabolism not only in
      obese subjects, but also in the non-obese.

PMID- 18344596
TI  - The effect of neonatal capsaicin treatment on the CGRP-immunoreaction in the
      trigeminal subnucleus caudalis of mice.
AB  - The calcitonin-gene related peptide (CGRP) is a primary afferent neurotransmitter
      in the trigeminal system. Although a neonatal administration of capsaicin
      eliminates substance P (SP)-mediated nociceptive responses to induce a permanent
      functional reduction in C-fibers, little information is available regarding
      changes in CGRP-immunoreaction in mice undergoing neonatal capsaicin treatment
      (CP mice). This study examined postnatal changes in the distribution of CGRP
      immunoreaction in the trigeminal subnucleus caudalis and trigeminal ganglion of
      CP mice by immunohistochemical technique and a quantitative analysis.
      Immunohistochemistry for CGRP in the subnucleus caudalis (Vc) demonstrated two
      dense distributions of neurons in the CP mice as well as naive mice: in the
      marginal layer and the region 400-600 mum deep. The quantitative analysis
      revealed no significant difference in the density of CGRP immunoreaction between
      naive and CP mice 1-8 weeks of age. In the trigeminal ganglion of both groups,
      the size distribution of CGRPpositive neurons displayed a distribution pattern
      with one peak in 200-300 mum(2) at week 1 and with two peaks in 200-300 mum(2)
      and 600-700 mum(2) at week 8 but no significant difference in neural density
      existed between these regions. When double staining in the naive mice with CGRP
      or SP and VR1, a capsaicin receptor, was done, many trigeminal ganglion neurons
      co-expressed SP- and VR1-immunoreactions, but rarely exhibited CGRP/VR1-co
      localization. Taken together with previous data, these current observations
      suggest that CGRP containing afferent neurons possibly performs differing roles
      in nociceptive afferent input transmission within the Vc from SP-containing
      neurons in mice.

PMID- 18344597
TI  - Changes in salivary physiological stress markers associated with winning and
      losing.
AB  - Using a representative table game popular in Japan known as shogi, or Japanese
      chess, we investigated the effects of winning and losing on saliva composition.
      The subjects were 90 healthy male university students who were members of a shogi
      club. Saliva samples were collected immediately before and after playing shogi,
      and again 30 min later. Salivary cortisol and testosterone levels in the samples
      were determined by ELISA and EIA, respectively. After finishing each game, the
      competitiveness of the game was evaluated using questionnaires. In the samples
      taken after playing shogi, there was an increase in the levels of salivary
      testosterone and cortisol, regardless of whether the subject won or lost, and the
      tendency was more pronounced in competitive games. There were no such changes in
      the control group, who did not play a game prior to providing the samples. Our
      results suggest that stress response is intimately linked with competition and
      could be used to determine which players are more capable of handing stress in a
      competitive environment.

PMID- 18344598
TI  - Induction of apoptosis by anti-CD44 antibody in human chondrosarcoma cell line
      SW1353.
AB  - Because chondrosarcoma is resistant to chemotherapy and ionizing radiation, the
      primary treatment of chondrosarcoma is surgical resection. Effective
      chemotherapeutic agents for chondrosarcoma are necessary. Although there is
      evidence that CD44 is involved in apoptosis susceptibility in several cell types,
      the effectiveness of anti-CD44 treatment on chondrosarcoma has never been
      studied. This study was aimed to clarify whether anti-CD44 monoclonal antibody
      induces apoptosis in human chondrosarcoma cell line SW1353. Confocal microscopy
      revealed that the SW1353 cells expressed CD44 that bound the anti-CD44 antibody
      IM7. Treatment of the cells with IM7 resulted in a significant decrease in cell
      viability, compared with that with control IgG. In contrast, IM7 failed to reduce
      cell viability in human chondrocytes. In SW1353 cells, IM7 induced chromatin
      condensation, nuclear fragmentation, and apoptotic body formation while control
      IgG had marginal effect. These data indicate that anti-CD44 treatment could
      induce apoptosis in chondrosarcoma cells.

PMID- 18344599
TI  - Pirh2 interacts with and ubiquitylates signal recognition particle receptor beta
      subunit.
AB  - Pirh2 is a RING finger type ubiquitin ligase which ubiquitylates various proteins
      including p53, p27(Kip1), HDAC1, and epsilon-COP. In this study, we identified
      signal recognition particle receptor beta subunit (SRbeta), an integral membrane
      protein of the endoplasmic reticulum (ER), as a novel Pirh2-interacting protein
      by yeast two-hybrid screening. We confirmed that Pirh2 interacted with SRbeta in
      mammalian cells. An immunofluorescent staining revealed that Pirh2 colocalized
      with SRbeta in the ER. Pirh2 poly-ubiquitylated SRbeta in an intact RING finger
      domain-dependent manner in vivo and in vitro. Unexpectedly, different from other
      Pirh2 substrates, neither overexpression of Pirh2 nor depletion of cellular Pirh2
      affected SRbeta protein stability. Pirh2 preferentially utilized lysine residues
      6 and 29 of the ubiquitin to mediate the formation of polyubiquitin chains on
      SRbeta. These results suggest that Pirh2 may regulate SRbeta function by
      mediating poly-ubiquitylation of SRbeta without affecting the stability of SRbeta
      protein per se.

PMID- 18344600
TI  - Phospholipase D is essential for keratocyte-like migration of NBT-II cells.
AB  - NBT-II cells on collagen-coated substrates move rapidly and persistently,
      maintaining a semi-circular shape with a large lamellipodium, in a manner similar
      to fish keratocytes. The inhibitor of phospholipase D (PLD), n-butanol,
      completely blocked the migration and disturbed the characteristic localization of
      actin along the edge of lamellipodia. To investigate the functional difference
      between the two isozymes of PLD (PLD1 and PLD2), we transfected NBT-II cells with
      vectors expressing shRNA to deplete PLD1 or PLD2. Depletion of both PLD1 and 2 by
      RNA interference reduced the velocity of the migration, but depletion of PLD2
      inhibited motility more severely than that of PLD1. Furthermore, GFP-PLD2 was
      localized to the protruding regions of lamellipodia in migrating cells. Thus, PLD
      is essential for the maintenance of keratocyte-like locomotion of NBT-II cells,
      presumably by regulating the actin cytoskeleton.

PMID- 18344601
TI  - [Guidelines and practices for ethical animal experiments].

PMID- 18344602
TI  - [Improvement of precision in pharmacological studies using the non-linear
      regression method: estimation of enzyme inhibition constants as an example].

PMID- 18344603
TI  - [Strategies for antimigraine agents].

PMID- 18344604
TI  - [Recent topics on migraine: issues of the current treatments and new drugs for
      the treatment of migraine].

PMID- 18344605
TI  - [Immunotoxicity study].

PMID- 18344606
TI  - Trimidox-induced apoptosis is mediated through induction of p53 in NALM-6 cells.
AB  - We examined the effect of trimidox-induced apoptosis involvement of p53 in the
      NALM-6 cell line of acute lymphoblastic leukemia. Trimidox has been shown to
      increase the induction of p53. Phosphorylation of p53 protein at Ser-15 and Ser
      20 residues was activated earlier than the obvious increase in p53 expression.
      Pifithrin-alpha, a p53 inhibitor, significantly prevented trimidox-induced
      apoptotic characteristics, as detected by nuclear morphological observation and
      DNA fragmentation. Trimidox-induced apoptosis was enhanced or attenuated by
      transfection with wild-type or dominant-negative p53 containing expression
      vectors, respectively. These results indicate that one of the induction
      mechanisms of apoptosis by trimidox is the mediated augmentation of p53.

PMID- 18344607
TI  - Mouse organic anion transporter 2 (mOat2) mediates the transport of short chain
      fatty acid propionate.
AB  - In this study, we have elucidated that propionate, one of the short chain fatty
      acids (SCFAs), is the transport substrate for murine organic anion transporter 2
      (mOat2), which is expressed in the kidneys and the liver. When expressed in
      Xenopus oocytes, mOat2-mediated [(3)H]PGE(2) transport was inhibited by three- to
      five-carbon SCFAs (C3 to C5). Among the SCFAs tested, propionate (3-carbon SCFA)
      was transported by mOat2 in a time-dependent manner. Since propionate is a potent
      glucogenic compound, Oat2 may be involved in the regulation of cellular
      metabolism through the transport of these metabolites in the kidneys and the
      liver.

PMID- 18344608
TI  - Glycyrrhizin inhibits interleukin-8 production and nuclear factor-kappaB activity
      in lung epithelial cells, but not through glucocorticoid receptors.
AB  - This study was designed to examine the glucocorticoid-like inhibitory effect of
      glycyrrhizin (GL) on interleukin (IL)-8 production in A549 lung epithelial cells.
      GL, as well as dexamethasone (DEX) inhibited both tumor necrosis factor (TNF)
      alpha- and IL-1beta-induced IL-8 production, mRNA expression, and promoter
      activity in A549 cells. Both GL and DEX inhibited transactivation of nuclear
      factor (NF)-kappaB, without inhibiting translocation of the NF-kappaB p65 subunit
      to the nucleus. However, the effect of GL was insensitive to RU486, a GR
      antagonist, and to GR knockdown by siRNA. Furthermore, only GL inhibited DNA
      binding of p65 to the IL-8 promoter region. These findings indicated that GL had
      a glucocorticoid-like inhibitory effect on IL-8 production via a mechanism that
      differs from that of glucocorticoids.

PMID- 18344609
TI  - Lafutidine facilitates calcitonin gene-related peptide (CGRP) nerve-mediated
      vasodilation via vanilloid-1 receptors in rat mesenteric resistance arteries.
AB  - Lafutidine is a histamine H(2)-receptor antagonist with gastric antisecretory and
      gastroprotective activity associated with activation of capsaicin-sensitive
      nerves. The present study examined the effect of lafutidine on neurotransmission
      of capsaicin-sensitive calcitonin gene-related peptide (CGRP)-containing
      vasodilator nerves (CGRPergic nerves) in rat mesenteric resistance arteries. Rat
      mesenteric vascular beds were perfused with Krebs solution and vascular
      endothelium was removed by 30-s perfusion with sodium deoxycholate. In
      preparations preconstricted by continuous perfusion of methoxamine (alpha(1)
      adrenoceptor agonist), perfusion of lafutidine (0.1 - 10 microM) concentration
      dependently augmented vasodilation induced by the periarterial nerve stimulation
      (PNS, 1 Hz) without affecting vasodilation induced by exogenous CGRP (10 pmol)
      injection. Perfusion of famotidine (H(2)-receptor antagonist, 1 - 100 microM) had
      no effect on either PNS-induced or CGRP-induced vasodilation. Perfusion of
      lafutidine concentration-dependently augmented vasodilation induced by a bolus
      injection of capsaicin (vanilloid-1 receptor agonist, 30 pmol). The presence of a
      vanilloid-1 receptor antagonist, ruthenium red (10 microM) or capsazepine (5
      microM), abolished capsaicin-induced vasodilation and significantly decreased the
      PNS-induced vasodilation. The decreased PNS-induced vasodilation by ruthenium red
      or capsazepine was not affected by perfusion of lafutidine. These results suggest
      that lafutidine facilitates CGRP nerve-mediated vasodilation by modulating the
      function of presynaptic vanilloid-1 receptors located in CGRPergic nerves.

PMID- 18344610
TI  - Cyclic ADP-ribose mediates formyl methionyl leucyl phenylalanine (fMLP)-induced
      intracellular Ca(2+) rise and migration of human neutrophils.
AB  - Although cyclic ADP-ribose (cADPR), a novel Ca(2+)-mobilizing mediator, is
      suggested to be involved in the functions of neutrophils in rodents, its role in
      human neutrophils remains unclear. The present study examined the ability of
      cADPR to mobilize Ca(2+) and mediate formyl methionyl leucyl phenylalanine (fMLP)
      stimulated increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) and
      migration in human neutrophils. cADPR induced Ca(2+) release from digitonin
      permeabilized neutrophils, and the release was blocked by 8Br-cADPR, an
      antagonist of cADPR. Immunophilin ligands, FK506 and rapamycin, but not
      cyclosporine A, inhibited cADPR-induced Ca(2+) release. 8Br-cADPR partially
      reduced fMLP-induced [Ca(2+)](i) rise and abolished the rise in combination with
      2APB, an IP(3)-receptor antagonist. Anti-CD38Ab and NADase that interfere with
      cADPR formation, reduced the fMLP-induced [Ca(2+)](i) rise. When beta-NAD(+), a
      substrate of ADP-ribosyl cyclase, and cADPR were added to the medium, the former
      gradually increased [Ca(2+)](i) and the latter potentiated the fMLP-induced
      [Ca(2+)](i) rise. The beta-NAD(+)-induced [Ca(2+)](i) rise in Ca(2+)-free medium
      was inhibited by anti-CD38Ab, 8Br-cADPR, FK506, ruthenium red, and thapsigargin.
      mRNAs of nucleoside transporter (NT), ENT1, ENT2, CNT, and CNT3 were expressed in
      neutrophils; and their inhibitors, inosine, uridine, and s-(4-nitrobenzyl)-6
      thioinosine, reduced the [Ca(2+)](i) rise induced by beta-NAD(+) and fMLP. fMLP
      timulated migration was inhibited by the removal of Ca(2+) from the medium or by
      the addition of 8Br-cADPR, anti-CD38Ab, NADase, and NT inhibitors. These results
      suggest that cADPR was synthesized extracellularly by CD38, transported into the
      cells through NTs, and then Ca(2+) was mobilized by FK506-binding protein
      dependent process. This process may be involved in fMLP-induced intracellular
      Ca(2+) signaling and migration in human neutrophils.

PMID- 18344611
TI  - Cholinergic regulation of orexin/hypocretin neurons through M(3) muscarinic
      receptor in mice.
AB  - The cholinergic system plays an important role in regulation of arousal and REM
      sleep. In the present study, we showed that a muscarinic receptor agonist,
      carbachol (CCh), activates almost 20% of orexin-producing neurons (orexin
      neurons), which play a critical role in maintenance of arousal. We also found
      that a very small population of orexin neurons (1%) was inhibited by CCh.
      Muscarinic receptor antagonists inhibited the CCh-induced activation of orexin
      neurons in a dose-dependent manner. The M(3)-selective muscarinic receptor
      antagonist 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) affected the
      response at a significantly lower concentration compared with the M(1)-selective
      muscarinic antagonist pirenzepine. IC(50) of 4-DAMP and pirenzepine was 0.30 +/-
      0.15 and 59.9 +/- 18.6 nM, respectively. The CCh-induced inward current was
      attenuated by the nonselective cation channel blocker SKF96365. These results
      indicate that CCh activates 20% of orexin neurons through the M(3) muscarinic
      receptor and subsequent activation of nonselective cation channels.

PMID- 18344612
TI  - Involvement of cyclooxygenase-2 in synergistic effect of cyclic stretching and
      eicosapentaenoic acid on adipocyte differentiation.
AB  - The present study examined the combined effects of fish-oil-derived omega-3
      polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), and cyclic stretching on the adipocyte
      differentiation of 3T3-L1 cells. Treatment with EPA alone did not inhibit the
      differentiation, although it partially suppressed the expressions of peroxisome
      proliferator-activated receptor (PPAR)-gamma(2) and CCAAT/enhancer-binding
      protein (C/EBP)alpha transcripts, which are considered to be indispensable for
      the determination of adipocyte differentiation. However, the differentiation was
      significantly reduced when EPA but not DHA was concomitantly applied with cyclic
      stretching. In addition, EPA, but not DHA, could be a substrate of cyclooxygenase
      (COX)-2, and we found that the stretching significantly augmented the expression
      of COX-2 and that a selective COX-2 inhibitor (NS-398) inhibited the combined
      effect of the stretching and EPA. Taken together, it appears that the stretching
      and EPA exhibit a synergistic effect for the inhibition of adipocyte
      differentiation through stretch-induced COX-2.

PMID- 18344613
TI  - Swallowing disorder and inhibition of cough reflex induced by atropine sulfate in
      conscious dogs.
AB  - In this study, the effects of atropine sulfate (atropine) on swallowing and cough
      reflex were evaluated in the two experimental models in conscious dogs. To
      evaluate the effects of atropine on swallowing, 1 mL of marker (contrast medium)
      was injected into the pharynx under X-ray exposure to induce swallowing.
      Baclofen, used as a positive control, caused marker congestion in the upper
      esophagus. In our experimental model, atropine (0.02 and 0.1 mg/kg, i.v.) dose
      dependently increased not only the number of marker congestions but also that of
      the swallows. In addition, atropine significantly shortened the onset of first
      swallowing. In the evaluation of atropine effects on electrically evoked cough
      reflex induced by two electrodes implanted into the trachea, atropine strongly
      inhibited the number of coughs at 0.01 or 0.05 mg/kg accompanied with 0.01 or
      0.05 mg/kg per hour (i.v.), respectively. These findings indicate that atropine
      has the potential of causing aspiration pneumonia through induction of swallowing
      disorder and inhibition of the cough reflex.

PMID- 18344614
TI  - Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich
      domains.
AB  - Human ubiquitin ligase HRD1 is involved in endoplasmic reticulum-associated
      degradation (ERAD). We recently reported that HRD1 interacts with Parkin
      associated endothelin receptor-like receptor (Pael-R), a substrate of Parkin, and
      promotes Pael-R degradation, resulting in the protection of cells from the lethal
      accumulation of Pael-R. However, except for RING-finger domain that is necessary
      for ubiquitin ligase activity, the roles of other human HRD1 domains are unclear.
      Here, we show that the proline-rich domain of HRD1 is necessary to promote the
      degradation of Pael-R and that the protein's transmembrane domain is necessary to
      transfer Pael-R from the endoplasmic reticulum (ER) to the cytosol. A HRD1 mutant
      defective in the transmembrane domain is markedly more unstable than wild-type
      HRD1. These results suggest that HRD1 has diverse functions besides ubiquitin
      ligase activity.

PMID- 18344615
TI  - Paraventricular alpha1- and alpha2-adrenergic receptors mediate hindbrain
      lipoprivation-induced suppression of luteinizing hormone pulses in female rats.
AB  - Acute central lipoprivation suppresses pulsatile luteinizing hormone (LH) release
      and increases blood glucose levels through noradrenergic input to the
      hypothalamic paraventricular nucleus (PVN) in female rats. The present study was
      conducted to identify adrenergic receptor subtypes involved in central
      lipoprivation-induced suppression of pulsatile LH secretion and increases in
      plasma glucose levels in female rats. Acute hindbrain lipoprivation was produced
      by injection into the fourth cerebroventricle (4V) of 2-mercaptoacetate (MA), an
      inhibitor of fatty acid oxidation, in estradiol-implanted ovariectomized rats.
      Two min before MA injection, alpha1-, alpha2- or beta-adrenergic receptor
      antagonist was injected into the PVN. Injection of MA into the 4V suppresses
      pulsatile LH release in PVN vehicle-treated rats, whereas pretreatment of animals
      with injection of alpha1- or alpha2-adrenergic antagonist into the PVN blocked
      the effect of the 4V MA injection on LH pulses. beta-Adrenergic antagonist did
      not affect MA-induced suppression of LH pulses. The counter-regulatory increase
      in plasma glucose levels after 4V MA injection was also partially blocked by
      pretreatment with alpha1- and alpha2-adrenergic receptor antagonists. These
      results suggest that alpha1- and alpha2-adrenergic receptors in the PVN mediate
      hindbrain lipoprivation-induced suppression of LH release and counter-regulatory
      increases in plasma glucose levels in female rats.

PMID- 18344616
TI  - Synergistic role of Igf2 and Dlk1 in fetal liver development and hematopoiesis in
      bi-maternal mice.
AB  - Mouse bi-maternal embryos (BMEs) that contain two haploid sets of genomes from
      non-growing (ng) and fully-grown (fg) oocytes develop to embryonic day (E) 13.5.
      However, the ng/fg BMEs never develop beyond E13.5 because of repression of the
      paternally expressed imprinted genes, Igf2 and Dlk1. The present study was
      conducted to address the issue of whether fetal hematopoietic disorder is
      involved in the restricted development of BMEs. FACS analysis revealed that the
      livers of ng(wt)/fg BMEs contained increased numbers of immature c-kit(+)/ter119(
      ) hematopoietic cells, were while the numbers of mature c-kit(-)/ter119(+)
      hematopoietic cells were decreased. This finding was supported by histological
      observations. Quantitative gene expression analysis revealed that Igf2 and Dlk1
      expression was repressed in the liver. To understand the role of paternally
      methylated imprinted genes on chromosomes 7 and 12, particularly Igf2 and Dlk1,
      in fetal liver hematopoiesis, we constructed ng(Deltach7)/fg, ng(Deltach12)/fg
      and ng(DeltaDouble)/fg BMEs using ng oocytes harboring deletion of differentially
      methylated regions at distal chromosomes 7 and/or 12. The ng(Deltach7)/fg,
      ng(Deltach12)/fg and ng(DeltaDouble)/fg BMEs, respectively, express Igf2, Dlk1
      and both, and these embryos developed to term with specific phenotypes; the
      ng(Deltach7)/fg and ng(Deltach12)/fg BMEs develop to term with severe growth
      retardation, and the ng(DeltaDouble)/fg BMEs can survive to become normal female
      adults. By inducing Igf2 and Dlk1 expression, the proportions of mature and
      immature hematopoietic cells in the livers of the ng(Deltach7)/fg,
      ng(Deltach12)/fg and ng(DeltaDouble)/fg BMEs were considerably restored, and
      particularly in the ng(DeltaDouble)/fg BMEs, hematopoiesis occurred normally with
      appropriate expressions of the related genes. These data suggest that
      inappropriate expression of Igf2 and Dlk1 is involved in impaired fetal
      hematopoiesis.

PMID- 18344617
TI  - Differential induction from X-irradiated human peripheral blood monocytes to
      dendritic cells.
AB  - Dendritic cells (DCs) are a type of antigen-presenting cell which plays an
      essential role in the immune system. To clarify the influences of ionizing
      radiation on the differentiation to DCs, we focused on human peripheral blood
      monocytes and investigated whether X-irradiated monocytes can differentiate into
      DCs. The non-irradiated monocytes and 5 Gy-irradiated monocytes were induced into
      immature DCs (iDCs) and mature DCs (mDCs) with appropriate cytokine stimulation,
      and the induced cells from each monocyte expressed each DC-expressing surface
      antigen such as CD40, CD86 and HLA-DR. However, the expression levels of CD40 and
      CD86 on the iDCs derived from the 5 Gy-irradiated monocytes were higher than
      those of iDCs derived from non-irradiated monocytes. Furthermore, the mDCs
      derived from 5 Gy-irradiated monocytes had significantly less ability to
      stimulate allogeneic T cells in comparison to the mDCs derived from non
      irradiated monocytes. There were no significant differences in the phagocytotic
      activity of the iDCs and cytokines detected in the supernatants conditioned by
      the DCs from the non-irradiated and irradiated monocytes. These results suggest
      that human monocytes which are exposed to ionizing radiation can thus
      differentiate into DCs, but there is a tendency that X-irradiation leads to an
      impairment of the function of DCs.

PMID- 18344618
TI  - Hypoxia-induced cardiac remodeling in sleep apnea syndrome: involvement of the
      renin-angiotensin-aldosterone system.

PMID- 18344619
TI  - Aortic pulse wave velocity and carotid-femoral pulse wave velocity: similarities
      and discrepancies.
AB  - The objectives of this study were to determine the relationship between carotid
      femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their
      modulators and association with coronary artery disease (CAD). We studied 107
      consecutive patients (68 men) with a mean age of 60.49+/-8.31 years who had
      stable angina and had been referred for coronary angiography. cfPWV and aPWV were
      measured simultaneously during cardiac catheterization using the Complior device
      and aortic pressure waveform recordings, respectively. Based on the presence or
      absence of significant coronary artery stenosis (CAS) patients were subdivided
      into a CAS+ or CAS- group. The mean values of cfPWV and aPWV were 10.65+/-2.29
      m/s and 8.78+/-2.24 m/s, respectively. They were significantly higher in the CAS+
      (n=71) compared with the CAS- (n=36) group and predicted significant CAS
      independently of cardiovascular risk factors and mean or systolic aortic blood
      pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the
      degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74,
      p<0.001) and CAS- group (r=0.46, p=0.003). Age and mean aortic blood pressure
      were independent predictors for aPWV as well as cfPWV. In the receiver operating
      characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in
      identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69,
      respectively; p=0.13). However, neither cfPWV nor aPWV was effective at
      differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly
      correlated parameters with similar determinants and comparable accuracy in
      predicting significant CAS. The strength of correlation between these two indices
      differed significantly between subjects with and those without CAS.

PMID- 18344620
TI  - Relationship between oxidative stress and essential hypertension.
AB  - This study investigated the association of blood pressure with blood oxidative
      stress-related parameters in normotensive and hypertensive subjects. A cross
      sectional design was applied to 31 hypertensive patients and 35 healthy
      normotensive subjects. All subjects were men between the ages of 35 and 60 years.
      Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and
      current use of any medication. All patients underwent 24-h ambulatory blood
      pressure monitoring and sampling of blood and urine. Antioxidant enzymes
      activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation
      (malondialdehyde) were determined in erythrocytes. Parameters measured in the
      plasma of test subjects were plasma antioxidant status, lipid peroxidation (8
      isoprostane), plasma vitamin C and E, and the blood pressure modulators renin,
      aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood
      pressures of hypertensives were negatively correlated with plasma antioxidant
      capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=
      0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes,
      and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of
      oxidative stress. Blood pressures showed a positive correlation with both plasma
      and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure
      modulator levels showed significant differences between the groups or correlation
      with blood pressures. These findings demonstrate a strong association between
      blood pressure and some oxidative stress-related parameters and suggest a
      possible role of oxidative stress in the pathophysiology of essential
      hypertension.

PMID- 18344621
TI  - Joint impact of smoking and hypertension on cardiovascular disease and all-cause
      mortality in Japan: NIPPON DATA80, a 19-year follow-up.
AB  - Hypertension and smoking are major risk factors for death due to cardiovascular
      disease (CVD). These attributions for CVD mortality should be higher in the
      countries where obesity-related conditions are uncommon. However, the joint
      effect of these risk factors on CVD and all-cause mortality have not been
      described. We followed a representative 8,912 Japanese men and women without a
      history of stroke and heart disease. Participants were categorized into 4 groups
      as follows: a group of individuals who neither smoked nor had hypertension (HT),
      a group of current smokers, a group with HT, and a group of current smokers with
      HT. We further calculated population-attributable fractions (PAF) of CVD and all
      cause mortality based on relative hazards assessed by proportional hazard
      regression models. After 19 years of follow-up, we observed 313 and 291 CVD and
      948 and 766 all-cause deaths for men and women, respectively. The PAF of CVD
      mortality due to smoking or HT were 35.1% for men and 22.1% for women. The PAF of
      CVD mortality was higher in participants <60 years of age (57.4% for men and
      40.7% for women) vs. those who were older (26.3% for men and 18.1% for women).
      Aggressive attempts to discourage smoking and to curb HT could yield large health
      benefits in Japan and throughout Asia, particularly for those aged <60 years.
      Efforts to warn about the adverse consequence of HT and smoking during
      adolescence and youth could yield the greatest health benefits, since positive
      behaviors adopted early are more easily continued into middle adulthood and later
      life.

PMID- 18344622
TI  - C-reactive protein, left ventricular mass index, and risk of cardiovascular
      disease in essential hypertension.
AB  - We examined the association between C-reactive protein (CRP) and left ventricular
      mass index (LVMI), and investigated prospectively the incidence of cardiovascular
      disease (CVD) in asymptomatic subjects with essential hypertension. A total of
      629 subjects (mean age 62 years, 51% female) free of prior CVD were included in
      this study. In cross-sectional analysis at baseline, patients were divided into
      three groups according to serum CRP levels: <1, 1 to 2, and >2 mg/L. In
      multivariate analysis, LVMI increased in a stepwise fashion with increasing CRP
      levels in both men (127.2+/-2.9, 138.7+/-4.1, 141.8+/-3.5 g/m(2), respectively;
      F=6.85, p=0.001) and women (119.5+/-3.6, 129.2+/-4.9, 130.2+/-4.8 g/m(2); F=4.23,
      p=0.031). During follow-up (mean 32 months), 52 subjects (19 female) developed
      CVD. Kaplan-Meier analysis with log-rank tests showed a significantly poorer
      event-free survival rate in the group with elevated CRP levels (> or =1 mg/L)
      (chi(2)=8.22, p<0.01) and that with left ventricular hypertrophy (LVH)
      (chi(2)=19.91, p<0.01). When participants were divided into four groups on the
      basis of CRP level (<1 or > or =1 mg/L) and the absence or presence of LVH, the
      group with LVH/CRP> or =1 mg/L showed markedly poorer event-free survival
      (chi(2)=28.02, p<0.01), and the adjusted hazard ratio by multivariate Cox
      regression analysis was 2.65 (95% confidence interval [CI]=1.55-5.46, p<0.01). In
      the subgroup with LVH (n=362), a significantly lower event-free survival rate of
      CVD was also observed in the group with CRP> or =1 mg/L (hazard ratio [HR] 1.37,
      95% CI: 1.02-1.85, p=0.025). Our findings demonstrate that the CRP level is
      independently associated with LVMI, and suggest that measurement of CRP may
      provide clinically important prognostic information to supplement LVH.

PMID- 18344623
TI  - Renal protective effect in hypertensive patients: the high doses of angiotensin
      II receptor blocker (HARB) study.
AB  - Angiotensin receptor blockers (ARBs) are the recommended first-line
      antihypertensive treatment for managing chronic kidney disease, and strict blood
      pressure (BP) regulation is crucial for the reduction of proteinuria. Valsartan
      and candesartan are commonly used ARBs in Japan, with maximum permissible doses
      of 160 mg/day and 12 mg/day, respectively. We evaluated BP and proteinuria after
      changeover from the maximum dose of candesartan to the maximum dose of valsartan,
      in 55 poorly controlled hypertensive patients undergoing candesartan treatment
      who were unable to achieve optimal BP according to the Japanese Society of
      Hypertension Guidelines for the Management of Hypertension (JSH 2004). We
      measured BP and pulse rate and assessed urinary protein excretion (UPE) before
      and after changeover. Changeover was associated with decreases in systolic BP and
      diastolic BP from 158/89 mmHg to 150/86 mmHg (p<0.01). Changeover was also
      associated with a reduction in UPE adjusted to urinary creatinine from 0.35+/
      0.19 g/g creatinine to 0.19+/-0.37 g/g creatinine (p=0.0271) in patients who had
      high urinary protein levels prior to changeover without significant decreases in
      BP (p=0.0184). According to multiple regression analysis, higher UPE (p<0.0001)
      and a lower glomerular filtration rate (GFR) (p=0.0011) prior to changeover were
      independently correlated with reduction in UPE. Our results suggest that the
      maximum dose of valsartan is more effective than the maximum dose of candesartan
      for reducing BP and proteinuria.

PMID- 18344624
TI  - Functional polymorphism of the myeloperoxidase gene in hypertensive
      nephrosclerosis dialysis patients.
AB  - Myeloperoxidase (MPO) may play an important role not only in host defense
      reactions but also in local inflammations, especially in atherosclerotic diseases
      such as hypertensive nephrosclerosis (HN). Paradoxically, MPO-deficient mice have
      been reported to show increased atherosclerosis compared with wild mice, although
      higher MPO levels are thought to exacerbate atherosclerotic disease. To clarify
      the genetic role of MPO in HN, we examined the function and distribution of the 
      463G/A polymorphism located in the promoter region of the MPO gene with ex vivo
      flow cytometry analysis and a study in end-stage renal disease patients,
      respectively. This polymorphism has been reported to have a functional
      significance in vitro, with the A allele being associated with lower MPO
      expression. In the present study, we also found significantly higher reactive
      oxygen species (ROS) production with peripheral neutrophils isolated from
      subjects with the GG genotype compared with those from subjects with other
      genotypes by flow cytometry assay with 2-[6-(4'-amino) phenoxy-3H-xanthen-3-on-9
      yl] benzoic acid (APF), which shows higher sensitivity with hypochlorite (OCl(
      )). Genotyping the -463G/A polymorphism in HN, chronic glomerulonephritis (CGN)
      and diabetic nephropathy (DM) patients who were under hemodialysis treatment
      demonstrated that the GG genotype was more frequent in the HN group than in the
      CGN and DM groups. However, the distribution of the GG genotype in the HN group
      was similar to that in healthy individuals. Although the -463G/A polymorphism is
      associated with ROS production, careful interpretation may be required to
      conclude that the -463G/A polymorphism can serve as a useful marker of
      atherosclerosis and cardiovascular events in dialysis patients.

PMID- 18344625
TI  - Effects of short-term hypocaloric diet on sympatho-vagal interaction assessed by
      spectral analysis of heart rate and blood pressure variability during stress
      tests in obese hypertensive patients.
AB  - We examined the effects of a short-term low-calorie diet on the activity of the
      autonomic nervous system during stress tests in obese patients with hypertension
      by analysis of heart rate and blood pressure variability. Eighteen obese
      inpatients with essential hypertension were given a regular-calorie diet (1,600
      kcal, NaCl 7 g) for 4 days, and then a low-calorie diet (1,100 kcal, NaCl 7 g)
      for 11 days. During both the regular-calorie diet and low-calorie diet, power
      spectral analysis of heart rate and blood pressure variability at rest and during
      mental arithmetic test, deep breathing test, isometric handgrip test or cold
      pressor test was performed. Body weight and 24-h ambulatory blood pressure were
      significantly lower during the low-calorie diet than during the regular-calorie
      diet. Systolic and diastolic blood pressure significantly increased over the
      handgrip test and cold pressor test during both diets. The low frequency
      component (LF) of systolic blood pressure, a marker of sympathetic activity to
      the vasculature, during the deep breathing test and cold pressor test were
      significantly lower on the low-calorie diet than the regular-calorie diet. The
      blood leptin concentration was also significantly lower on the low-calorie diet
      than the regular-calorie diet. The decrease in body weight was positively
      correlated with the decrease in blood leptin concentration. The LF/high frequency
      component (HF) ratio of the RR interval at rest on the regular-calorie diet was
      negatively correlated with the decrease in blood leptin concentration. These
      results suggest that the autonomic nervous function assessed by analysis of heart
      rate and blood pressure variability during stress tests may be improved by weight
      loss due to a short-term low-calorie diet in obese patients with hypertension.

PMID- 18344626
TI  - Telmisartan treatment decreases visceral fat accumulation and improves serum
      levels of adiponectin and vascular inflammation markers in Japanese hypertensive
      patients.
AB  - Hypertension contributes to the occurrence and progression of cardiovascular
      diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to
      activate the peroxisome proliferator-activated receptor gamma and improve insulin
      sensitivity. We investigated the effects of telmisartan treatment on visceral
      fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive
      patients. This was an open-label, non-controlled study. Twenty-eight essential
      hypertensive patients (22 men and 6 women; age 60.6+/-1.9 years; body mass index
      [BMI] 25.5+/-0.6 kg/m(2)) participated. Fat area was assessed with computerized
      tomography. All the subjects were started on telmisartan 40 mg/day, which was
      increased to 80 mg/day to achieve the blood pressure target of less than 130/80
      mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin
      levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan
      treatment. There were significant reductions in visceral fat area (from 103.1+/
      7.9 to 93.3+/-8.4 cm(2), p<0.01) and pulse wave velocity (from 1,706+/-52 to
      1,587+/-51 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum
      high-density lipoprotein cholesterol (from 5.06+/-0.15 to 5.32+/-0.13 mmol/L,
      p<0.05) and adiponectin levels (from 8.27+/-0.76 to 9.13+/-0.81 microg/mL,
      p<0.05) were observed. Also, there were reductions in the interleukin-6 level
      (from 2.26+/-0.27 to 1.60+/-0.14 pg/mL, p<0.01). We also conducted these
      investigations in male subjects alone and similar findings were obtained for all
      of these parameters. In conclusion, telmisartan treatment was associated with an
      improvement of vascular inflammation, reductions in visceral fat and increases in
      serum adiponectin.

PMID- 18344627
TI  - Independent determinants of second derivative of the finger photoplethysmogram
      among various cardiovascular risk factors in middle-aged men.
AB  - The second derivative of the finger photoplethysmogram (SDPTG) has been used as a
      non-invasive examination for arterial stiffness. The present study sought to
      elucidate independent determinants of the SDPTG among various cardiovascular risk
      factors in middle-aged Japanese men. The SDPTG was obtained from the cuticle of
      the left-hand forefinger in 973 male workers (mean age: 44+/-6 years) during a
      medical checkup at a company. The SDPTG indices (b/a and d/a) were calculated
      from the height of the wave components. Multiple logistic regression analyses
      revealed that the independent determinants of an increased b/a (highest quartile
      of the b/a) were age (odds ratio [OR]: 1.12 per 1-year increase, 95% confidence
      interval [CI]: 1.09-1.15), hypertension (OR: 1.65, 95% CI: 1.03-2.65),
      dyslipidemia (OR: 1.51, 95% CI: 1.09-2.09), impaired fasting glucose/diabetes
      mellitus (OR: 2.43, 95% CI: 1.16-5.07), and a lack of regular exercise (OR: 2.00,
      95% CI: 1.29-3.08). Similarly, independent determinants of a decreased d/a
      (lowest quartile of the d/a) were age (OR: 1.11 per 1-year increase, 95% CI: 1.08
      1.14), hypertension (OR: 3.44, 95% CI: 2.20-5.38), and alcohol intake 6 or 7 days
      per week (OR: 2.70, 95% CI: 1.80-4.06). No independent association was observed
      between the SDPTG indices and blood leukocyte count or serum C-reactive protein
      levels. In conclusion, the SDPTG indices reflect arterial properties affected by
      several cardiovascular risk factors in middle-aged Japanese men. The association
      between inflammation and the SDPTG should be evaluated in further studies.

PMID- 18344628
TI  - Angiotensin II receptor blocker reduces oxidative stress and attenuates hypoxia
      induced left ventricular remodeling in apolipoprotein E-knockout mice.
AB  - Elevated superoxide formation in cardiac extracts of apolipoprotein E-knockout
      (apoE-KO) mice has been reported. In addition, we previously reported that
      hypoxia increased oxidative stress in the aortas of apoE-KO mice, although we did
      not examine the effect of hypoxia on the heart. The aim of this study was to
      investigate the effect of chronic hypoxia on the left ventricular (LV) remodeling
      in apoE-KO mice treated with or without an angiotensin II receptor blocker. Male
      apoE-KO mice (n=83) and wild-type mice (n=34) at 15 weeks of age were kept under
      hypoxic conditions (oxygen, 10.0+/-0.5%) and treated with olmesartan (3
      mg/kg/day) or vehicle for 3 weeks. Although LV pressure was not changed, hypoxia
      caused hypertrophy of cardiomyocytes and increased interstitial fibrosis in the
      LV myocardium. Furthermore, nuclear factor-kappaB (NF-kappaB) and matrix
      metalloproteinase (MMP)-9 activities were increased in apoE-KO mice exposed to
      chronic hypoxia. Olmesartan effectively suppressed the 4-hydroxy-2-nonenal
      protein expression and NF-kappaB and MMP-9 activities, and preserved the fine
      structure of the LV myocardium without affecting the LV pressure. In conclusion,
      olmesartan reduced oxidative stress, and attenuated the hypoxia-induced LV
      remodeling, in part through the inhibition of NF-kappaB and MMP-9 activities, in
      apoE-KO mice.

PMID- 18344629
TI  - Inhibition of vascular angiotensin-converting enzyme by telmisartan via the
      peroxisome proliferator-activated receptor gamma agonistic property in rats.
AB  - The angiotensin receptor blocker (ARB) telmisartan is a partial agonist of
      peroxisome proliferator-activated receptor gamma (PPARgamma). Typical PPARgamma
      agonists suppress the gene expression of angiotensin-converting enzyme (ACE) in
      vascular tissues. However, it remains unclear whether or not PPARgamma activation
      by telmisartan can inhibit vascular ACE activity. We compared the effects of
      PPARgamma agonistic telmisartan and non-agonistic valsartan on ACE, vascular
      function and oxidative stress in stroke-prone spontaneously hypertensive rats
      (SHR-SP) and in sodium (1% NaCl)-loaded SHR-SP. SHR-SP and sodium-loaded SHR-SP
      received placebo, 1 mg/kg telmisartan, or 10 mg/kg valsartan for 2 weeks.
      Systolic blood pressure (SBP) was equally reduced in SHR-SP given either
      telmisartan or valsartan compared with SHR-SP given placebo. However, neither
      telmisartan nor valsartan suppressed SBP in sodium-loaded SHR-SP. Acetylcholine
      induced significantly less vasorelaxation in SHR-SP than in Wistar-Kyoto rats,
      but telmisartan and valsartan each significantly prevented such vasorelaxation.
      However, telmisartan significantly attenuated acetylcholine-induced
      vasorelaxation in sodium-loaded SHR-SP, whereas valsartan did not. Telmisartan
      significantly attenuated NADPH oxidase subunit p22(phox) gene expression in both
      SHR-SP and sodium-loaded SHR-SP, whereas valsartan did not. Likewise, telmisartan
      also significantly attenuated the significantly increased vascular ACE activity
      in sodium-loaded SHR-SP, whereas valsartan did not. In conclusion, the partial
      PPARgamma agonist telmisartan might inhibit vascular ACE activity, and result in
      the prevention of oxidative stress and endothelial dysfunction more effectively
      than non-agonistic valsartan.

PMID- 18344630
TI  - Gene polymorphism of myospryn (cardiomyopathy-associated 5) is associated with
      left ventricular wall thickness in patients with hypertension.
AB  - We examined a gene polymorphism of a novel Z-disc-related protein, myospryn
      (cardiomyopathy-associated 5). We focused on one haplotype block associated with
      a tag single nucleotide polymorphism (SNP) that covered 16 of 27 coding SNPs with
      linkage disequilibrium (minor allele frequency 0.413). Screening a myospryn
      polymorphism (K2906N) in a general health check-up of a rural Japanese population
      revealed an association with cardiac diseases (p=0.0082). In further analysis of
      the interaction between K2906N and cardiac function in patients, K2906N was
      associated with the anteroseptal wall thickness of the left ventricle in a
      recessive model (p=0.0324) and with the ratio of the peak velocity of the early
      diastolic filling wave to the peak velocity of atrial filling (A/E) (p=0.0278).
      In an association study based on left ventricular wall thickness, we found a
      significant difference in the K2906N genotype between controls and patients with
      cardiac hypertrophy. These results suggest that the K2906N polymorphism could be
      clinically associated with left ventricular hypertrophy and diastolic dysfunction
      independent of known parameters. Although the precise mechanism underlying this
      association remains to be elucidated, treatment with angiotensin II induced an
      increase in heart myospryn mRNA level in vitro and in vivo. Our results suggest
      that the polymorphism of myospryn is associated with left ventricular
      hypertrophy, and an association between a Z-disc protein and cardiac adaptation
      in response to pressure overload.

PMID- 18344631
TI  - Angiotensin-converting enzyme inhibitor suppresses activation of calcineurin in
      renovascular hypertensive rats.
AB  - Accumulating evidence suggests an important role of the calcineurin signaling
      pathway in mediating the development of cardiac hypertrophy. It has also been
      reported that angiotensin-converting enzyme inhibitors (ACEIs) regressed cardiac
      hypertrophy in some animal and human models. In this study, we investigated the
      possible role of calcineurin in the regression of cardiac hypertrophy induced by
      the ACEI perindopril in rats with renovascular hypertension. The effect of the
      calcineurin inhibitor cyclosporine A (CsA) was also studied. Starting from 2
      months after a two-kidney one-clip (2K1C) procedure, the rats that had developed
      progressive left ventricular (LV) hypertrophy were daily administered perindopril
      (1 mg/kg per day) or CsA (20 mg/kg per day) until 3 months. At the end of either
      treatment, the LV gravimetric, morphometric and histological measurements
      revealed the regression of LV hypertrophy; and the enzymatic assay, Western
      blotting and reverse transcription-polymerase chain reaction (RT-PCR) showed that
      both calcineurin activity and the calcineurin protein and mRNA expression levels
      were significantly decreased compared with untreated 2K1C rats, but that LV
      systolic performance was unchanged by either treatment. These data suggest that
      the cardiac hypertrophy regression induced by the ACEI perindopril is likely
      mediated, at least in part, through inhibition of the calcineurin signaling
      pathway.

PMID- 18344632
TI  - Systemic distribution of salusin expression in the rat.
AB  - Salusin-alpha and salusin-beta are multifunctional bioactive peptides with
      hypotensive and bradycardic effects. They were originally identified from full
      length human cDNAs by bioinformatics analyses. Salusin peptides are expressed in
      human tissues at the mRNA level, but no information is available about their
      systemic distributions in any species. We examined the distributions of
      preprosalusin mRNA and the salusin peptides in a variety of normal rat organs.
      Whereas preprosalusin mRNA was expressed ubiquitously, immunoreactive salusin
      beta was detected most strongly in the hypothalamus and posterior pituitary, and
      less abundantly in the anterior pituitary and gastrointestinal, immune, and
      hematopoietic systems. Salusin-beta-positive cells appeared to be of either
      hematopoietic or endocrine origin, and many hematopoietic cells were also stained
      with anti-CD68, which specifically recognizes macrophages. Salusin-alpha-like
      immunoreactivity was not detected in any of the rat tissues. These results
      indicate that rat salusin is immunologically similar to human salusin-beta and
      widely expressed, especially in the immune, gastrointestinal, and central nervous
      systems and mainly in endocrine- and hematopoietic-derived cells.

PMID- 18344633
TI  - Torsades de Pointes: a rare complication of an extra-adrenal pheochromocytoma.
AB  - Pheochromocytoma is an infrequent secondary cause of arterial hypertension, often
      associated with paroxysmal headache, sweating, weight loss, and palpitations.
      Cardiovascular complications of pheochromocytoma include sudden death, heart
      failure due to toxic cardiomyopathy, and hypertensive encephalopathy. Here we
      report the case of a female with an acquired long-QT-syndrome as a rare
      complication of an extra-adrenal pheochromocytoma. Diagnosis was made after
      sotalol-induced Torsades de Pointes.

PMID- 18344634
TI  - Association of serum adiponectin levels with all-cause mortality in hemodialysis
      patients.
AB  - OBJECTIVE: Adiponectin (ADPN) has been shown to protect against cardiovascular
      disease for the general population with problematic metabolic syndrome. However,
      it remains unclear whether ADPN is associated with mortality in patients on
      maintenance hemodialysis (HD). METHODS, PATIENTS OR MATERIALS: We selected 85 HD
      patients [51 men/34 women; mean age, 64+/-2 years; underlying kidney diseases,
      diabetic nephropathy in 36 patients (42.3%), chronic glomerulonephritis in 29
      (34.1%), hypertensive nephrosclerosis in 10 (11.8%), and others in 10 (11.8%)]
      who survived for more than 3 months after the start of HD. We first measured
      serum ADPN levels and prospectively followed patients for the next 3 years.
      RESULTS: We were able to follow 74 of 85 patients; 59 survived, and 15 died.
      Serum log-transformed ADPN levels were negatively correlated with BMI (r=-0.43,
      p<0.01). Despite a similar BMI (20.7+/-0.8 vs. 20.3+/-0.4 kg/m(2)), the expired
      patients had significantly higher ADPN compared with the surviving patients (20.5
      microg/ml [14.0-23.5] vs. 14.2 microg/ml [9.7-21.3], p<0.05). Cox-hazards
      multivariate regression analysis adjusted for conventional case-mix features
      (age, sex, and underlying kidney disease) revealed that serum ADPN became a
      significant determinant of all-cause mortality. There was a 10.3% risk increment
      for each 1-microg/ml increase in ADPN during the follow-up. Kaplan-Meier analysis
      revealed that patients with higher ADPN levels (> or =15 microg/ml) had a
      significantly lower survival rate compared with those with lower ADPN levels (<15
      microg/ml) (76 vs. 92%, p<0.05). CONCLUSION: These results indicated that high
      rather than low ADPN independently predict total mortality in HD patients.

PMID- 18344635
TI  - A prospective and randomized study for improvement of acute asthma by non
      invasive positive pressure ventilation (NPPV).
AB  - OBJECTIVE: We hypothesized that non-invasive positive pressure ventilation (NPPV)
      would improve an acute asthma attack in mild to moderate cases without
      bronchodilator therapy. METHODOLOGY: A total of 44 eligible patients with acute
      asthma of mild to moderate severity who had acute attacks were randomly allocated
      to a NPPV (n=30) or control group (n=14). Both groups received intravenous
      infusion of hydrocortisone prior to the study. Patients in the NPPV group were
      divided into two subgroups at random: a high- (n=16) and a low-pressure group
      (n=14). The former had a fixed expiratory positive airway pressure and
      inspiratory positive airway pressure of 6 cmH2O and 8 cmH2O, respectively, while
      the latter had levels of 4 cmH2O and 6 cmH2O, respectively. Effects on the
      following variables were assessed: FEV(1), oxygen saturation, heart rate,
      respiratory rate, scores of accessory muscle use and wheezing by auscultation,
      modified Borg scale score, and mean intra-airway pressure on the monitor.
      RESULTS: A total of 26 patients completed the study in the NPPV group. The mean
      percent change in FEV(1) significantly improved after 40 minutes in the high
      pressure group compared with that in the control group (p<0.0001). Similar
      significant improvements in modified Borg scale score and physical examination
      findings were observed in the high- and low-pressure groups. None of the patients
      required re-hospitalization or return to the emergency room in either the NPPV or
      control group. CONCLUSION: We conclude that higher inflation pressure on NPPV led
      to clinical improvement in patients with acute asthma attacks of mild to moderate
      severity.

PMID- 18344636
TI  - Clinical efficacy of the transdermal tulobuterol patch in patients with chronic
      obstructive pulmonary disease: a comparison with slow-release theophylline.
AB  - BACKGROUND: There is insufficient evidence for the efficacy of a transdermal
      tulobuterol patch (TP), although combination therapy with bronchodilators is
      recommended for chronic obstructive pulmonary disease (COPD). OBJECTIVE: A
      randomized, controlled crossover study was conducted to evaluate the clinical
      efficacy and safety of the TP in 16 patients with COPD. Slow-release theophylline
      was used as a control drug. METHODS: Following a 2-week run-in period, patients
      were randomly allocated to two groups by the envelope method; they then received
      the TP and theophylline for 4 weeks each by the crossover method. Pulmonary
      function tests, peripheral blood examination, and electrocardiography were
      performed before and after each treatment period. Patients recorded in diaries
      their symptom scores, numbers of administrations of inhaled beta(2) agonists, and
      presence/absence of adverse reactions. RESULTS: Patients receiving TP exhibited
      significant improvement in the number and ease of sputum expectoration and in
      cough frequency score and wheezing severity score compared with baseline
      (p<0.05); the corresponding improvement in patients receiving theophylline was
      non-significant. Assessment of quality of life by the St. George's Hospital
      Respiratory Questionnaire revealed that treatment with TP was associated with
      significant improvement in symptoms, impact, and total scores compared with
      baseline (p<0.05); theophylline gave only a non-significant improvement in total
      score. Neither drug caused significant changes in the results of physiological
      examinations or in pulse or blood pressure. There was no difference in safety
      between the treatments. CONCLUSION: Treatment of COPD patients with TP is more
      effective than with theophylline.

PMID- 18344637
TI  - Treatment of severe pulmonary hypertension secondary to scleroderma: a three-drug
      approach.
AB  - We present a case of scleroderma complicated by severe pulmonary hypertension.
      The use of a three-drug (bosentan, iloprost, and sildenafil) approach contributed
      to significant improvement of both the clinical conditions and the pulmonary
      hemodynamics. Combining three pulmonary vasodilators with different mechanisms of
      action could benefit patients with severe pulmonary hypertension resistant to
      conventional therapy.

PMID- 18344638
TI  - Latent hypoparathyroidism in an osteoporotic patient with multiple
      endocrinopathies and secondary hemochromatosis due to multiple blood
      transfusions, unmasked by alendronate and glucocorticoid at adrenal crisis.
AB  - A 30-year-old normocalcemic man with hypopituitarism, hypogonadism, diabetes
      mellitus, and secondary hemochromatosis due to multiple blood transfusions was
      admitted because of adrenal crisis. After intravenous administration of saline
      and cortisol, the corrected serum level of calcium decreased to 7.3 mg/dl. This
      osteoporotic patient had been prescribed alendronate for radial bone fracture.
      Since the increase in intact PTH (68 pg/ml) was impaired compared to that seen in
      hypocalcemic patients with secondary hyperparathyroidism, we presume that the
      patient has had latent hypoparathyroidism, which was unmasked by the
      administration of glucocorticoid and bisphosphonate. With a supplemented dose of
      1alpha-OHD3, the patient has been eucalcemic.

PMID- 18344639
TI  - Ruptured arterial aneurysm of the kidney in a patient with microscopic
      polyangiitis.
AB  - We present the case of a 55-year-old man with ruptured arterial aneurysm
      accompanied by microscopic polyangiitis in the kidney. He was admitted to our
      hospital because of general fatigue, fever and serious numbness of his
      extremities. Microscopic polyangiitis (MPA) was diagnosed on the basis of
      cardinal symptoms, including rapidly progressive glomerular nephritis, peripheral
      nerve disorder and the lung abnormality, as well as positive MPO-ANCA findings.
      Hemodialysis had to be started on admission because of renal failure. Renal
      biopsy demonstrated necrotizing glomeruli, crescent formation with interstitial
      infiltrates. There were no immune deposits on immunofluorescence study or
      electron micrographs. The pathological diagnosis was necrotizing
      glomerulonephritis involving small and medium-sized arteries. He was treated with
      intravenous semi-pulse methylprednisolone therapy because of the intensely
      pathological renal activation and the abnormal shadow on chest X-ray. The
      inflammatory reaction subsequently improved, MPO-ANCA decreased and the lung
      lesions diminished. He complained of sharp pain of sudden onset on his left side.
      His hemoglobin dropped from 9.8 g/dl to 6.0 g/dl developed in the subsequent
      hours, but there were no sign of hemorrhage. Abdominal CT scan showed a large
      left-sided perinephric, intracapsular hematoma. Selective arterial angiography
      showed multiple aneurysms in renal and hepatic arteries. No active bleeding was
      present and he recovered with transfusion, supportive therapy and monitoring
      alone. Multiple aneurysms detected by angiography in the renal and hepatic
      arteries showed improvement. He is currently stable on regular hemodialysis
      treatment with a low dose of oral prednisolone.

PMID- 18344640
TI  - Eosinophilic pneumonia (EP) associated with rheumatoid arthritis in which drug
      induced eosinophilic pneumonia could be ruled out.
AB  - A 72 year-old man. He was diagnosed with rheumatoid arthritis in 2002. In January
      2005 he noted productive cough and fever; he was diagnosed as eosinophilic
      pneumonia (EP). We discontinued administration of bucillamine and methotrexate
      and started to treat with oral prednisolone 30 mg daily. To rule out drug-induced
      EP, prednisolone was tapered by 10 mg per week. Consolidation occurred in the
      right lower lobe when prednisolone was decreased to 5 mg daily. After increasing
      the dose of prednisolone to 30 mg daily again, consolidation was promptly
      resolved. It was considered to be important to rule out drug-induced EP.

PMID- 18344641
TI  - Recurrent gefitinib-induced interstitial lung disease.
AB  - Gefitinib, the epidermal growth factor receptor tyrosine kinase inhibitor, is
      effective for patients with non-small cell lung cancer. However, a serious
      adverse effect, interstitial lung disease (ILD), has been reported. The re
      administration of gefitinib might be considered when there is no other choice of
      treatment and a therapeutic effect can be expected; however, there is no
      published data on the safety of restarting gefitinib after its discontinuation in
      cases suspected of having gefitinib-induced ILD. We report a case with recurrent
      gefitinib-induced ILD, which suggests that re-administration of gefitinib should
      be considered cautiously in patients who have previously developed gefitinib
      induced ILD.

PMID- 18344642
TI  - Sarcoidosis in the setting of idiopathic chronic bronchiolitis with airway
      colonization from P. aeruginosa: treatment with low-dose macrolides.
AB  - It has long been suggested that infectious agents may trigger sarcoidosis through
      their infectious or antigenic properties. A patient with airway colonization from
      P. aeruginosa in the setting of idiopathic bronchiolitis (IB) mimicking diffuse
      panbronchiolitis (DPB) developed sarcoidosis. Impressive clinical and
      radiological improvement of both bronchiolitis and sarcoidosis features was
      achieved with a one-year treatment with low-dose erythromycin, thus suggesting a
      possible link between the two conditions in this specific case. Pathogenic
      hypotheses and therapeutic implications are specifically discussed.

PMID- 18344643
TI  - Nephrotic syndrome due to primary systemic AL amyloidosis, successfully treated
      with VAD (vincristine, doxorubicin and dexamethasone) alone.
AB  - We report 3 patients with nephrotic syndrome ascribed to primary systemic AL
      amyloidosis that were successfully treated with VAD (vincristine, doxorubicin and
      dexamethasone) alone. M-protein in serum disappeared soon after VAD, and
      nephrotic syndrome gradually improved in parallel with a decrease in daily
      protein excretion in urine. Long-term follow-up of these patients showed neither
      relapse of nephrotic syndrome nor reappearance of M-protein. High-dose melphalan
      followed by autologous stem cell support is a standard therapy for primary
      systemic AL amyloidosis, but in high-risk cases for this treatment, such as
      elderly patients and those with multiple organ involvement, VAD might be a
      therapeutic option.

PMID- 18344644
TI  - Acute oculogyric crisis in a patient taking clebopride.
AB  - We present a 21-year-old woman with an oculogyric crisis following the
      administration of clebopride. Based on the temporal relationship of the
      administration of clebopride to the occurrence of the event and the absence of
      other possible etiologies, clebopride is implicated as the cause of this acute
      oculogyric crisis, despite the fact that a cause-and-effect relationship cannot
      be confirmed.

PMID- 18344645
TI  - Necrotizing fasciitis caused by Pseudomonas aeruginosa.
AB  - An 85-year-old man patient was admitted to the hospital complaining of fever and
      bilateral leg pain with swelling and erythema. A laboratory investigation
      revealed leukocytopenia, thus suggesting sepsis. Gram negative rods were detected
      in the specimen from the affected skin and empiric antibacterial therapy was
      initiated. The following day, his symptoms worsened and Pseudomonas aeruginosa
      was isolated from the blood culture and the skin specimen. Magnetic resonance
      imaging (MRI) did not show the typical characteristics of necrotizing fasciitis.
      In spite of intensive medical treatment, the patient's condition became critical,
      and on day 10 after admission, he died of multiple organ failure. An autopsy
      revealed necrotizing fasciitis due to P. aeruginosa. This is a rare case and its
      clinical presentation was atypical. The clinical diagnosis of this infection may
      be difficult, and therefore such cases warrant the careful attention of
      physicians.

PMID- 18344646
TI  - Pancreatico-gastric fistulas due to intraductal papillary mucinous neoplasm
      (IPMN).

PMID- 18344647
TI  - Calcified occlusion of the coronary arteries in a young woman diagnosed with
      Kawasaki disease.

PMID- 18344648
TI  - Right ventricular collapse caused by a dilated retrosternal gastric tube.

PMID- 18344649
TI  - A rare case of pyogenic liver abscess complicated with cardiac tamponade.

PMID- 18344650
TI  - Linear calcification in the cortico-medullary junction of the kidney.

PMID- 18344651
TI  - Terry's nails as a part of aging.

PMID- 18344652
TI  - [The risk assessment of mycotoxins and its international trends].

PMID- 18344653
TI  - [Investigation and culture of microbial contaminants of Caulerpa lentillifera
      (Sea Grape)].
AB  - Caulerpa lentillifera is a kind of edible seaweed, known as 'sea grape' or 'green
      caviar'. It is used in fresh salads. However, it is sensitive to low temperature
      and osmotic pressure, and is easily spoilt by storage in a refrigerator or
      washing with tap water. That is the reason why it is difficult to prevent food
      poisoning, especially due to Vibrio parahaemolyticus. In this study we
      investigated of marine bacteria and V. parahaemolyticus in C. lentillifera and
      cultured them in order to develop effective control of bacteria in commercial
      farms. The sixteen farms in the Okinawa Islands were investigated from August to
      September in 2006. A total of 176 samples were collected from eleven points
      during the cultivation processes and from the products. About 10(3) cfu/mL of
      marine bacteria were detected in the seawater used in the tank culture, but after
      cultivation of C. lentillifera the number had increased to about 10(6) cfu/mL.
      The number of marine bacteria in C. lentillifera did not change significantly
      through the process of planting to the final product (about 10(7) cfu/g). V.
      parahaemolyticus was detected in seawater from all processes and C. lentillifera
      was isolated from 56% of seawater, 25% of seed-stocks, and 18.8% of product
      samples, though but thermostable direct hemolysin gene was not detected from
      enrichment cultures or isolated V. parahaemolyticus strains. These results
      indicate that for prevention of food poisoning by V. parahaemolyticus in C.
      lentillifera, it is important to establish a suitable sterilization procedure for
      each process.

PMID- 18344654
TI  - Development of event-specific quantitation method for GA21 maize, which is a gm
      event without CaMV35S promoter.
AB  - A real-time PCR detection method was developed for event-specific quantitation of
      Roundup Ready maize, GA21. The developed PCR method was designed to amplify an
      artificial junction site between the native maize genome DNA and the recombinant
      DNA of GA21 maize, which provides only one target sequence per haploid of GA21
      genome. Thus, the amplification efficiency of the event-specific target for GA21
      became closely similar to the amplification of SSIIb, and the conversion factor
      (Cf) for the quantitation method was similar to the theoretical value. The
      developed method demonstrated better performance than the existing construct
      specific method that has been used as a Japanese official method. The developed
      method can easily be combined with the real-time PCR targeting of the CaMV35S
      promoter, and the multiplexed method should be an effective screening method for
      GM maize.

PMID- 18344655
TI  - [Detection of wheat as an allergenic substance in food by a nested PCR method].
AB  - A nested PCR method was developed for the detection of DNAs extracted from
      allergenic substances (here, wheat) in food. Because of DNA fragmentation,
      detection of wheat-specific DNA extracted from food, such as retort pouch food,
      is very difficult. Therefore, to improve the sensitivity of detection, a nested
      PCR primer pair (Wtr01NE2-5' and Wtr10NE5-3': amplicon size 97 bp) was newly
      designed within the region of the PCR products amplified by the official Japanese
      primer pair (Wtr01-5' and Wtr10-3'; amplicon size 141 bp) for wheat. Genomic DNAs
      of seven kinds of commercial processed foods containing wheat, wheat flour and
      three kinds of wheat flours pressure-heated at 100, 121 and 131 degrees C were
      extracted with a commercial ion-exchange type kit by modifying the Japanese
      official method. The nested PCR method involved two PCR procedures. First, PCR
      was performed by varying both the PCR reagents and cycling conditions of the
      Japanese official method. Second, PCR was performed using the first PCR products
      diluted 200-fold with TE buffer. The Japanese official method enabled detection
      of only four of the seven kinds of foods and three of the four kinds of flours
      (one sample was just a trace), while the nested PCR method detected all seven
      foods and all four flours. Investigation of the detectability of the four kinds
      of wheat flours depending on the size of the amplified fragment using five primer
      pairs showed that its size must be kept to less than approximately 100 bp. The
      nested PCR method significantly improved the sensitivity of detection of wheat
      specific DNA.

PMID- 18344656
TI  - [Simultaneous determination of neotame, alitame and aspartame in foods by HPLC].
AB  - Simultaneous determination of three artificial sweeteners, neotame (NE), alitame
      (AL) and aspartame (APM) in various foods by high-performance liquid
      chromatography (HPLC) was developed. Chopped or homogenized samples were packed
      into cellulose tubing with 0.01 mol/L hydrochloric acid containing 10% sodium
      chloride, and dialyzed against 0.01 mol/L hydrochloric acid for 24-48 hours. The
      dialyzate was passed through an Oasis MCX cartridge, and the cartridge was washed
      with water and methanol. Then the three sweeteners were eluted from the cartridge
      with a mixture of 0.5 mol/L ammonium chloride-acetonitrile (3 : 2). The
      sweeteners were separated on a Cosmosil 5C18-AR column using a gradient mode with
      a mobile phase of 0.01 mol/L phosphate buffer (pH 4.0)-acetonitrile and were
      detected at 210 nm. The recoveries of NE, AL and APM from 8 kinds of foods spiked
      with 10 and 100 microg/g were 86-100% and 89-104%, respectively. The detection
      limits of NE, AL and APM were 1 microg/g in samples. Furthermore, the three
      sweeteners were successfully identified by using liquid chromatography with
      tandem mass spectrometry.

PMID- 18344657
TI  - [Rapid determination of residues of 4 tetracyclines in meat by a microbiological
      screening, HPLC and LC/MS/MS].
AB  - A rapid and precise determination residues of 4 tetracyclines (TCs)
      (oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC) and
      doxycycline (DOXY)) in meat was developed by employing three analyses; a
      microbiological screening, HPLC and LC/MS/MS. TCs were extracted with pH 4.0
      McIlvaine buffer containing 0.01 mol/L EDTA from a meat sample, and then purified
      using a mixed mode, reversed-phase and cation-exchange cartridge. The mean
      recoveries (n=5) of 0.2 microg/g OTC, TC and CTC, 0.05 microg/g DOXY spiked in
      meat samples were 76.6-99.0% (C.V. 1.6-5.4%). In 13 meat samples in which the
      microbiological screening indicated the presence of TCs, CTC (9 samples) and DOXY
      (4 samples) were identified with HPLC and LC/MS/MS.

PMID- 18344658
TI  - [Method for DNA extraction and purification from corn-processed food using an ion
      exchange resin type kit].
AB  - The yield of genomic DNA extracted from corn-processed foods, such as corn flake
      and one of the corn snack what is called "Jumbo corn", using an ion-exchange
      resin type kit (Gtip) has been reported to be very low, and it is thought to be
      difficult to detect the intrinsic corn gene "Zein" in the foods. Therefore, we
      developed a new method using Gtip, which we called the "KNG-Gtip method," by
      modification of the Ministry of Health, Labour and Welfare (MHLW) method using
      Gtip (MHLW-Gtip method). We compared the KNG-Gtip method, MHLW-Gtip method, the
      Gtip method for detection of allergen (ALG-Gtip method), and the Gtip method
      according to the Ministry of Agriculture, Forestry and Fisheries (MAFF) (JAS-Gtip
      method) in terms of the yield and quality of genomic DNA and the detection
      probabilities of the PCR-amplified Zein gene. The concentrations of DNA and the
      detection probabilities of the PCR-amplified Zein gene of genomic DNA extracted
      from 4 g corn flake and 4 g Jumbo corn by the KNG-Gtip method were larger than
      those by using the conventional methods. In addition, the PCR-amplified Zein gene
      from 4 g of corn starch could be detected by the KNG-Gtip method. We propose that
      the KNG-Gtip method, in which requires sample weight of four grams, is practical
      and useful to extract genomic DNA from corn flake and Jumbo corn.

PMID- 18344659
TI  - [Effects of excess folic acid on growth and metabolism of water-soluble vitamins
      in weaning rats].
AB  - In order to determine the tolerable upper intake level of folic acid in humans,
      we investigated the effects of excessive folic acid administration on the body
      weight gain, food intake, tissue weight, and metabolism of B-group vitamins in
      weaning rats. The rats were freely fed ordinary diet containing 0.0002% folic
      acid (control diet) or the same diet with 0.01%, 0.1%, or 1.0% folic acid for 29
      days. The body weight gains and food intakes did not differ among the four
      groups. Diarrhea was not seen even in the 1.0% group. Excess folic acid did not
      affect the tissue weights of the brain, heart, liver, kidney, spleen, lung, or
      testis, or urinary excretion of other B-group vitamins. These results clearly
      showed that feeding a diet containing up to 1.0% folic acid did not affect the
      food intake, body weight gain, tissue weight, or urinary excretion of B-group
      vitamins in weaning rats.

PMID- 18344660
TI  - [Survey of synthetic disinfectants in grapefruit seed extract and its compounded
      products].
AB  - Grapefruit seed extract (GSE), derived from the seeds of grapefruit (Citrus
      paradisi MCAF.), is listed as a natural food additive in Japan. Products
      containing GSE are used as disinfectants made from only natural sources,
      especially after Japanese researchers found that GSE prevents the growth of
      norovirus. On the other hand, recent overseas studies indicated that synthetic
      disinfectants, such as benzalkonium and benzethonium chlorides, were present in
      some commercial GSE products. To confirm the quality of commercial GSE products
      available in Japanese markets, we carried out comprehensive research to identify
      the major constituents of commercial GSE products which are used as food
      additives (13 products from 6 manufacturers), dietary supplements (5 products
      from 4 manufacturers), cosmetic materials (16 products from 10 manufacturers) and
      disinfectant or deodorant sprays (7 products from 7 manufacturers). By means of
      NMR and LC/MS analysis, synthetic disinfectants such as benzethonium or
      benzalkonium salts were detected in most of the commercial GSE products.

PMID- 18344661
TI  - Genetically modified organisms: do the benefits outweigh the risks?
AB  - The objective of this literature review is to analyze the implications of using
      genetically modified organisms (GMOs) as well as international and European
      position regarding such organisms. METHOD: Review of international and European
      legal requirements and ethical guidelines and relevant publications, found and
      accessed with the help of PubMed and Lund University Library databases. RESULTS:
      The article discusses the main application areas of GMOs, the expansion of using
      GMOs in the world as well as the advantages and disadvantages of the implications
      of their usage. It further provides an overview of the suggested ways to tackle
      or avoid the GMO-related risks. The international and European positions
      regarding the application of GMOs are discussed and European Directives,
      Regulations, and ethical guidelines are overviewed. The article further presents
      the public attitudes towards GMOs in Europe as well as overviews surveys
      conducted at the national level. CONCLUSION: Suggested steps to tackle the
      challenge of developing and managing biotechnology for the benefit of public
      health and the environment are presented.

PMID- 18344662
TI  - [Association of metabolic syndrome with abnormalities of bulbar conjunctival
      vessels].
AB  - AIM: To examine and evaluate the relationships of the metabolic syndrome and
      abnormalities of bulbar conjunctival vessels among middle-aged Kaunas population.
      MATERIAL AND METHODS: Analysis was performed on 383 asymptomatic persons aged 38
      39 years (170 men and 212 women). Metabolic syndrome was defined using criteria
      of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP
      III). For determination of abnormalities in bulbar conjunctiva vessels and
      microcirculation, each participant underwent noncontact slit lamp examination.
      The changes of vessel walls and bloodstream, extravasal alterations were
      evaluated, and conjunctival index was calculated. RESULTS: Metabolic syndrome was
      present in 10.7% of individuals. Persons with metabolic syndrome had a 2.35-point
      higher conjunctival index compared to the controls (P=0.003). After evaluation of
      various components of metabolic syndrome to conjunctival index, it was determined
      that the greatest change in the means of conjunctival index was due to
      hyperglycemia (P=0.02) and central obesity (P=0.05). Metabolic syndrome was
      related to venular dilatation (OR=3.78; 95% CI, 1.86-7.72), arteriolar narrowing
      (OR=1.98; 95% CI, 0.97-4.09), decreased arteriolar-venular ratio (OR=2.35; 95%
      CI, 1.13-4.98), and increased venular tortuosity (OR=2.24; 95% CI, 1.06-4.82).
      Multiple logistic analysis revealed that venular dilatation (OR=3.38; 95% CI,
      1.43-7.99) and arteriolar narrowing (OR=2.22; 95% CI, 0.98-5.01) were significant
      factors in the prognosis of metabolic syndrome. CONCLUSIONS: Metabolic syndrome
      was significantly related to abnormalities of bulbar conjunctival vessels such as
      venular dilatation, arteriolar narrowing, decreased arteriolar-venular ratio, and
      increased venular tortuosity. Both conjunctival index and individual conjunctival
      microvascular changes may be prognostic factors for metabolic syndrome, but long
      term studies on associations between metabolic syndrome and changes of bulbar
      conjunctival vessels are needed.

PMID- 18344663
TI  - [A prospective comparison of double- and single-bundle anterior cruciate ligament
      reconstructions].
AB  - OBJECTIVE: A nonrandomized clinical study was performed to compare the clinical
      and radiological outcome between double-bundle and single-bundle anterior
      cruciate ligament (ACL) reconstructions with semitendinosus tendon in athletes.
      MATERIAL AND METHODS: We examined 70 patients with unilateral anterior cruciate
      ligament injury. They were followed up for a mean of 24 months. Each group of 35
      patients underwent either double- or single-bundle ACL reconstruction. The mean
      age of the patients was 24.7 years (range, 18-35 years). There were no
      differences between two groups regarding age at surgery, sex, follow-up period,
      period before surgery, combined meniscus injuries, athletic activity level, and
      International Knee Documentation Committee (IKDC) and Tegner scores. All patients
      followed the same postoperative program. They were evaluated using manual knee
      laxity tests, knee extension and flexion strength testing. General knee condition
      was evaluated by the IKDC and Tegner scores. RESULTS: The results were excellent
      and good in 32 (91.4%) patients after double-bundle ACL reconstruction and in 30
      (85.7%) patients after single-bundle ACL reconstruction, evaluating by IKDC
      system. However, statistical analysis showed no significant difference between
      the two groups regarding all IKDC-categorized data (P=0.87). The average scores
      of Tegner activity in double-bundle and single-bundle groups were 8.0 and 8.1,
      respectively. CONCLUSIONS: This trial showed no significant difference between
      the double and single-bundle ACL repairs.

PMID- 18344664
TI  - Significance of intracranial pressure and cerebral perfusion pressure in severe
      pediatric traumatic brain injury.
AB  - The aim of the study was to evaluate outcome of children after severe traumatic
      brain injury treated according to intracranial pressure (ICP)-targeted protocol,
      to define threshold values of peak ICP and minimal cerebral perfusion pressure
      (CPP) for decompressive osteoplastic craniotomy, and to determine the
      relationship between ICP, CPP and long-term outcome in these children. All
      children admitted to Pediatric Intensive Care Unit of Kaunas University of
      Medicine Hospital after severe head injury from January 2004 to June 2006 and
      treated according to ICP-targeted protocol for the management of severe head
      trauma were prospectively included in the study. Raised ICP was defined as a
      level higher than 20 mmHg. Minimal CPP was considered to be at a level of 40
      mmHg. Outcome was defined using Glasgow Outcome Scale (GOS) at discharge from the
      hospital and after 6 months. Forty-eight patients (32 boys and 16 girls) were
      included into the study. Favorable outcome (GOS score of 4 and 5) after 6 months
      was achieved in 43 (89.6%) cases. Mean peak ICP was 24.2+/-7.2 mmHg and mean
      minimal CPP - 53.1+/-14.7 mmHg. Decompressive craniotomy was performed in 13
      cases. Threshold values of peak ICP and minimal CPP for decompressive craniotomy
      were 22.5 mmHg (area under the curve, 0.880) and 46.5 mmHg (area under the curve,
      0.898), respectively. The differences in peak ICP and minimal CPP in groups of
      favorable and unfavorable outcomes were not statistically significant. Treating
      children after severe traumatic brain injury according to the ICP-targeted
      protocol for the management of severe pediatric traumatic brain injury resulted
      in a favorable long-term outcome.

PMID- 18344665
TI  - [Thickness of cerebral cortex measured using anatomical mesoscopic imaging and
      magnetic resonance imaging].
AB  - OBJECTIVE: Magnetic resonance imaging method opened up the possibility for in
      vivo examination of the anatomy of human brain. For this reason it is interesting
      and relevant to compare the knowledge accumulated over a number of years during
      the examination of the composition of dead brain to that obtained from magnetic
      resonance images. The aim of this study was to determine and compare the
      thickness of cerebral cortex in human of different age and sex, measured in
      different sites of the hemispheres when applying anatomical mesoscopic imaging
      and magnetic resonance imaging. MATERIAL AND METHODS: The thickness of cerebral
      cortex was measured in symmetrical Brodmann's areas of both hemispheres. The
      anatomical mesoscopic imaging technique was used for the examination of 2x2-cm
      cortex samples obtained during autopsy and fixed for 4 weeks in 10%
      paraformaldehyde. In these samples, cortex thickness was measured in sections
      perpendicular to the convolution, using an operative microscope, in a mesoscopic
      image at x16 magnification and with an accuracy of 0.01 mm. Using cerebral
      magnetic resonance imaging, the thickness of cerebral cortex in live subjects was
      measured on T1-weighted images of patients examined at the Clinic of Radiology,
      Kaunas University of Medicine Hospital. The measured cortical field image was
      magnified to the smallest element of digital image - the pixel - and measured
      with an accuracy of 0.01 mm. Each of the two techniques was applied for the
      examination of 20 men and women who were divided into age groups of 20-60 years
      (n=10) and older than 60 years (n=10). RESULTS AND CONCLUSIONS: Both examination
      methods yielded a statistically significant difference in the thickness of
      cerebral cortex between Brodmann's areas 1, 4, and 19. No significant difference
      in cortex thickness was found between different age and sex groups; however, the
      findings showed that the difference in cortex thickness between the different age
      male groups was 4.6% and female - 1.6%. No significant difference using different
      techniques was found, but the cortex thickness in the fixed samples was reduced
      by 0.5 cm on average.

PMID- 18344666
TI  - Subacute effects of cadmium and zinc ions on protein synthesis and cell death in
      mouse liver.
AB  - OBJECTIVE: The aim of this study was to evaluate in vivo the effects of cadmium
      and zinc ions on translational machinery and death of mouse liver cells. MATERIAL
      AND METHODS: Outbred mice received intraperitoneal injections of cadmium chloride
      solution (1.4 micromoles cadmium per 1 kg of body weight) and/or zinc sulfate
      solution (4.8 micromoles zinc per kg of body weight) three times per week for six
      weeks. Analogical volume of saline solution was injected to the control mice.
      Protein synthesis was evaluated by incorporation of [(14)C]-labeled leucine into
      peptides and proteins. Total tRNAs were isolated using deproteinized extract of
      liver tissue. Postmitochondrial supernatant was as a source of leucyl-tRNA
      synthetase. Activities of tRNA(Leu) and leucyl-tRNA synthetase were measured by
      an aminoacylation reaction using [(14)C]-labeled leucine. Liver cell apoptosis
      was detected by TUNEL assay using in situ cell death detection kit. RESULTS: A
      decrease in incorporation of [(14)C]-labeled leucine into proteins was detected
      in liver, kidney, and heart as well as diminution of tRNA(Leu) acceptor activity
      in cadmium-exposed liver. Cadmium caused activation of the leucyl-tRNA synthetase
      and induced liver cell apoptosis. Pretreatment of mice with zinc sulfate solution
      favored to protection of protein synthesis and acceptor activity of tRNA(Leu)
      against cadmium-induced inhibition. Under co-exposure of mouse liver to cadmium
      and zinc, activity of the leucyl-tRNA synthetase was at the level of control.
      Zinc did not influence TUNEL-positive cell number in cadmium-exposed mouse liver.
      CONCLUSIONS: Under subacute intoxication of mice by cadmium, zinc ions protect
      the translation machinery against inhibition, but do not decrease the number of
      apoptotic cells in the liver.

PMID- 18344667
TI  - [The incidence and diagnostics of congenital heart defects in Kaunas infant
      population during 1999-2005].
AB  - The objective of this study was to determinate the incidence and diagnostics of
      congenital heart defects in Kaunas infant population in 1999-2005 and to compare
      the data obtained with the data of years 1995-1998. SUBJECT AND METHODS: The
      study population comprised all newborns born in Kaunas city during 1999-2005.
      Congenital heart defects were registered based on clinical diagnosis after its
      verification using the data from consulting centers and pediatric outpatient
      departments. To assess the incidence of congenital heart malformations in newborn
      population, we conducted a validated newborn register based on maternal
      residential district. Modern epidemiological methods were used for data analysis.
      RESULTS: In 1999-2005, there were 24 069 live births in Kaunas: 2231 newborns
      were born with congenital anomalies, 198 had congenital heart malformations. The
      incidence of congenital heart defects was 8.2 per 1000 live newborns. The
      majority of congenital heart malformations were diagnosed in delivery units
      (93.94%). We have analyzed the relationship between birth weight and gestational
      age of newborns with congenital heart malformations. Newborns with low birth
      weight were at significantly higher risk of congenital heart malformation than
      newborns with normal birth weight (OR=3.52, 95% CI, 2.25-5.47). Our data also
      showed that newborns born before 32 weeks of gestation had a 5-fold increased
      risk of congenital heart malformation (OR=5.20; 95% CI, 2.50-10.84) and infants
      born before 37 weeks of gestation had a 4-fold increased risk (OR=4.08; 95% CI,
      2.68-6.19) compared with newborns born after 37 weeks of gestation. CONCLUSIONS:
      This study shows that incidence of congenital heart anomalies in Kaunas newborn
      population was 8.2 cases per 1000 live newborns in 1999-2005. It was determined
      that during 1999-2005, the number of above-mentioned anomalies diagnosed in
      delivery units increased by 23%.

PMID- 18344668
TI  - [Psychological factors of delinquent adolescent girls and suicide attempters].
AB  - The aim of this study was to study and compare externalizing and internalizing
      difficulties, clinical problems of adolescent girls who attempted a suicide and
      delinquent girls. A total of 100 adolescent girls aged 11-18 years have
      participated in this study: 50 of them were suicide attempters, and the other 50
      girls had problems of delinquent behavior. In this study, the questionnaire ASEBA
      YSR 11-18 was used. To compare averages, Student's t and Mann-Whitney's U tests
      were applied with a 0.05 level of statistical significance. For adolescent girls
      who attempted a suicide, more prominent internal difficulties were identified.
      They were more depressive/anxious, presented more somatic complains, and were
      more closed/anxious. Those girls felt more anxiety and presented more affective
      problems. The difference in the average scores of scales of the both groups was
      statistically significant (P<0.05). Externalizing problems of adolescent suicide
      attempters did not significantly differ from ones of the girls with delinquent
      behavior. The average scores of scales on braking of rules and aggression were
      not significantly different. Girls with delinquent behavior had a higher social
      competency, and the girls who attempted a suicide more often presented
      significant social difficulties, though there was no statistically significant
      difference in the scores on the activity competence scale. CONCLUSIONS: The
      adolescent girls who attempted a suicide have more evident internal difficulties
      than delinquent girls do, though externalizing behavior difficulties of the
      suicide attempters are similar to those of girls with delinquent behavior. The
      girls who attempted a suicide experience more social difficulties, and their
      social competency is lower when comparing to delinquent girls of the same age.

PMID- 18344669
TI  - Enrichment of the educational environment with information and communication
      technologies: state of art at the Faculty of Pharmacy of Kaunas University of
      Medicine.
AB  - Both traditional and new educational environments, the latter enriched with
      information and communication technologies, coexist in today's university. The
      goal of this article is to present the concept of educational environment
      enriched with information and communication technologies, to reveal the main
      features of such environment, and to present the results of certain investigation
      on the application of information technologies in teaching/learning processes at
      the Faculty of Pharmacy of Kaunas University of Medicine. The discussion object
      of this paper is the educational environment enriched with information and
      communication technologies. In designing the environments of this type, positive
      aspects of traditional teaching models are being developed by integrating them
      into the new educational environment. The concept of educational environment
      enriched with information and communication technologies is reviewed in the first
      part of this paper. The structure and main features of educational environments
      enriched with information and communication technologies are highlighted in the
      second part. The results of the study on the application of information
      technologies in teaching/learning processes at the Faculty of Pharmacy of Kaunas
      University of Medicine are presented in the third part.

PMID- 18344670
TI  - [Vasopressin for treatment of hemodynamic disorders].
AB  - Vasopressin is a 9-amino acid peptide synthesized by magnocellular neurons of the
      hypothalamus and released from posterior pituitary gland. The primary
      physiological role of vasopressin is the maintenance of fluid homeostasis. In
      this review, the classification of vasopressin receptors, namely V1 vascular, V2
      renal, V3 pituitary, oxytocin receptors, and purinergic receptors, and the
      effects of vasopressin on vascular smooth muscles, the heart, and the kidneys are
      discussed. Mortality rates of vasodilatory (or distributive), for example septic
      shock, are high. The use of vasopressin is an alternative therapy for
      vasodilatory shock with better outcome. Vasopressin is effective in resuscitation
      of adults after ventricular fibrillation or pulseless tachycardia, when
      epinephrine is not effective.

PMID- 18344672
TI  - Changing patterns of serum and bile antibodies in re-infected rats with
      Clonorchis sinensis.
AB  - Rats develop strong resistance to re-infection and super-infection by Clonorchis
      sinensis. The present study investigated the antibodies present in the sera and
      bile juice of rats that were primary infected and re-infected with C. sinensis.
      The serum level of specific IgG antibodies, which were elevated 2 wk of the
      primary infection, peaked at 4 wk and subsequently remained unchanged even during
      re-infection. The total IgE level in serum increased slowly from 388 ng / ml to
      3,426 ng / ml beginning 2 wk after the primary infection, and remained high up to
      8 wk but dropped to a normal level (259 ng / ml) after treatment. In resistant re
      infected rats, the serum IgE level increased rapidly and peaked within 1 wk,
      whereas no increase was observed in immunosuppressed rats. The serum level of
      specific IgA antibodies was elevated beginning 1 wk after infection, and
      decreased 4 wk after treatment. The total bile IgA level unchanged during the
      primary infection but increased in treated and re-infected rats. The elevated
      levels of serum IgE and bile IgA indicate that these immunoglobulins may be
      correlated with the development of resistance to re-infection by C. sinensis in
      rats.

PMID- 18344671
TI  - RNA interference in infectious tropical diseases.
AB  - Introduction of double-stranded RNA (dsRNA) into some cells or organisms results
      in degradation of its homologous mRNA, a process called RNA interference (RNAi).
      The dsRNAs are processed into short interfering RNAs (siRNAs) that subsequently
      bind to the RNA-induced silencing complex (RISC), causing degradation of target
      mRNAs. Because of this sequence-specific ability to silence target genes, RNAi
      has been extensively used to study gene functions and has the potential to
      control disease pathogens or vectors. With this promise of RNAi to control
      pathogens and vectors, this paper reviews the current status of RNAi in
      protozoans, animal parasitic helminths and disease-transmitting vectors, such as
      insects. Many pathogens and vectors cause severe parasitic diseases in tropical
      regions and it is difficult to control once the host has been invaded.
      Intracellularly, RNAi can be highly effective in impeding parasitic development
      and proliferation within the host. To fully realize its potential as a means to
      control tropical diseases, appropriate delivery methods for RNAi should be
      developed, and possible off-target effects should be minimized for specific gene
      suppression. RNAi can also be utilized to reduce vector competence to interfere
      with disease transmission, as genes critical for pathogenesis of tropical
      diseases are knockdowned via RNAi.

PMID- 18344673
TI  - A survey of ectoparasite infestations in stray dogs of Gwang-ju City, Republic of
      Korea.
AB  - This study was designed to investigate the incidence of ectoparasite infestation
      among stray dogs in Gwang-ju City, Republic of Korea. A total of 103 stray dogs
      collected in the Animal Shelter of Gwang-ju City from November 2003 to August
      2005 were investigated in this study. Ectoparasites of one or more genera were
      detected in 45.6% (47 / 103) of the dogs examined for dermatologic lesions and/or
      skin scrapings (from 3-5 affected areas). Otodectes cynotis was found to be the
      most frequent parasite (22.3%, 23 / 103), followed by Sarcoptes scabiei var canis
      (19.4%, 20 / 103), Ctenocephalides canis (6.8%, 7 / 103), Demodex canis (4.9%, 5
      / 103), and Trichodectes canis (1.0%, 1 / 103). Monospecific infestation was
      found in 83.0% (39 / 47) of the affected dogs, whereas concurrent infestations
      with 2 or more ectoparasites per animal were found in 17.0% (8 / 47) of the
      affected dogs. Trichodectes canis is reported for the first time in the Republic
      of Korea. Dogs less than 1 yr old were more heavily infected than other age
      groups (66.7%), and small-sized dogs of less than 3 kg body weight were more
      heavily infected than larger dogs (41.7%).

PMID- 18344674
TI  - Seroprevalence of toxocariasis among healthy people with eosinophilia.
AB  - The aim of this study is to determine the Toxocara seropositive rate among
      healthy people with eosinophilia. A total of 97 people residing in Seoul who were
      healthy and whose blood eosinophilia was over 10%, as shown by regular health
      check-ups in 2004, were subjected to this study. Their sera were tested by
      immunoblotting and ELISA with the antigen of larval Toxocara canis excretory
      secretory (ES) protein. Sixty-five sera were band-positive (67.0%). The
      seropositve control sera were positive to band sizes of 66 kDa, 56 kDa, 32 kDa,
      and 13 kDa. In ELISA, 63 sera (65.0%) were positive to T. canis ES protein. There
      was no significant correlation between the IgG ELISA titer and the level of
      eosinophilia (r = 0.156, P = 0.156). As there were insufficient data to determine
      whether there were cross-reactions with other helminthic infections, or whether
      atopy occurred, further studies are required to verify the cause of the
      seropositive reactions against T. canis ES antigen. Toxocariasis seropositivity
      is suggested to be the major cause of eosinophilia, since the Toxocara
      seroprevalence among Korean rural adults was shown to be approximately 5%.

PMID- 18344675
TI  - A laboratory-based study for first documented case of urinary myiasis caused by
      larvae of Megaselia scalaris (Diptera: Phoridae) in Saudi Arabia.
AB  - Megaselia scalaris (Diptera: Phoridae) is one of the medically important insects.
      Maggots from a urine sample of a 5-year-old Saudi girl were examined
      microscopically for identification. These maggots were cultured to become adult
      flies. Larvae and adults were identified using standard keys. Protozoan
      flagellates were obtained from the gut of the larvae. This is the first report of
      M. scalaris as a causative agent of urinary human myiasis in Saudi Arabia.

PMID- 18344676
TI  - Effect of iron on adherence and cytotoxicity of Entamoeba histolytica to CHO cell
      monolayers.
AB  - Iron is an essential element for almost all living organisms. The possible role
      of iron for growth, adherence and cytotoxicity of Entamoeba histolytica was
      evaluated in this study. The absence of iron from TYI-S-33 medium stopped amebic
      growth in vitro. However, iron concentrations in the culture media of 21.4-285.6
      microM did not affect the growth of the amebae. Although growth was not retarded
      at these concentrations, the adhesive abilities of E. histolytica and their
      cytotoxicities to CHO cell monolayer were correlated with iron concentration.
      Amebic adhesion to CHO cell monolayers was significantly reduced by low-iron
      (24.6 +/- 2.1%) compared with 62.7 +/- 2.8 and 63.1 +/- 1.4% of amebae grown in a
      normal-iron and high-iron media, respectively. E. histolytica cultured in the
      normal- and high-iron media destroyed 69.1 +/- 4.3% and 72.6 +/- 5.7% of cultured
      CHO cell monolayers, but amebae grown in the low-iron medium showed a
      significantly reduced level of cytotoxicity to CHO cells (2.8 +/- 0.2%). Addition
      of divalent cations other than iron to amebic trophozoites grown in the low-iron
      medium failed to restore levels of the cytotoxicity. However, when E. histolytica
      grown in low-iron medium were transferred to normal-iron medium, the amebae
      showed completely restored cytotoxicity within 7 days. The result suggests that
      iron is an important factor in the adherence and cytotoxicity of E. histolytica
      to CHO cell monolayer.

PMID- 18344677
TI  - The ruddy turnstone, Arenaria interpres interpres, a new definitive host for
      Gynaecotyla squatarolae (Digenea: Microphallidae).
AB  - The ruddy turnstone, Arenaria interpres interpres, a migratory Korean bird, was
      proved to be a natural definitive host for Gynaecotyla squatarolae (Digenea:
      Microphallidae). The ruddy turnstone was found dead at the seashore of Okgueup,
      Gunsan-si, Jeollabuk-do. The intestinal tract was examined, and 98 unknown flukes
      were recovered. The worms were 600 284 micrometer in size, and had 2 ventral
      suckers. The seminal vesicle was large, the genital atrium was prominent, and the
      average egg size was 20 12.5 micrometer. Based on these results, the worms were
      identified as G. squatarolae. This is the first report on the ruddy turnstone as
      a natural definitive host of G. squatarolae in the Republic of Korea.

PMID- 18344678
TI  - Evaluation of the Korean isolate-1 tachyzoite antigen for serodiagnosis of
      toxoplasmosis.
AB  - To evaluate the usefulness of the Korean Isolate-1 (KI-1) antigen for
      serodiagnosis of toxoplasmosis, antigen profiles of KI-1 tachyzoites were
      analyzed in comparison with RH tachyzoites by SDS-PAGE and immunoblotting. ELISA
      was performed on latex agglutination (LA)-positive and negative serum samples
      using KI-1 and RH antigens. Immunoblotting of the KI-1 antigen showed multiple
      antigen bands with molecular sizes of 22-105 kDa. Among them, 1 and 6 common
      bands were noted against a KI-1-infected and a RH-infected human serum,
      respectively, which represented differences in antigenic profiles between KI-1
      and RH tachyzoites. However, all 9 LA-positive human sera were found positive by
      ELISA, and all 12 LA-negative sera were negative by ELISA; the correlation
      between the ELISA titers and LA titers was high (r = 0.749). Our results suggest
      that tachyzoites of KI-1 may be useful for serodiagnosis of human toxoplasmosis.

PMID- 18344679
TI  - Centrocestus formosanus (Digenea: Heterophyidae) encysted in the freshwater fish,
      Puntius brevis, from Lao PDR.
AB  - The metacercariae of Centrocestus formosanus, a minute intestinal trematode of
      mammals and birds, were detected in the freshwater fish, Puntius brevis, from
      Vientiane Municipality, Lao PDR. The metacercariae were experimentally fed to
      mice, and adult flukes were recovered in their small intestines 7 days later. The
      adult flukes were morphologically characterized by having 32 (rarely 34)
      circumoral spines arranged in 2 alternative rows, a large bipartite seminal
      vesicle, an oval-shaped ovary, and an X-shaped excretory bladder. Based on these
      characters, the adults were identified as Centrocestus formosanus (Nishigori,
      1924). The taxonomic significance of C. formosanus, in relation to a closely
      related species, C. caninus (Leiper, 1913), is briefly discussed. It has been
      first verified by adult worm recovery that C. formosanus is prevalent in
      Vientiane areas of Lao PDR, taking the freshwater fish, P. brevis, as a second
      intermediate host.

PMID- 18344680
TI  - Cancer stem cell and cancer stemloids: from biology to therapy.
AB  - It has become a cliche that cancer therapy fails because it does not target rare
      cancer stem cells (CSCs). Here we are discuss that this is not how therapy fails
      and not any cancer cell with stem-like properties is CSC. Paradoxically, CSCs
      must be resting to explain their resistance to therapy yet must be cycling to
      explain their persistence in cell culture. To solve contradictions, this article
      introduces the term cancer stemloids (or stem cell-like cells) to describe
      proliferating self-renewing cells. The stem cell hierarchy (stem--proliferating-
      terminal cells) exists exactly to separate self-renewal (immortality) from
      proliferation. Cancer stemloids break the stem cell hierarchy and eventually may
      replace other cells. While CSC is shielded from any selective pressure and
      therefore unable to drive tumor progression, cancer stemloids undergo clonal
      selection, accumulate mutations, thus determining tumor progression and
      therapeutic failures. Unlike CSC, cancer stemloids are a crucial target for
      cancer therapy, exactly because they proliferate. Furthermore, two normally
      mutually-exclusive properties (proliferation and stemness) provide a means to
      design therapy to kill cancer stemloids selectively without killing normal stem
      and non-stem cells. In contrast, true CSCs are not only a difficult, but also an
      insufficient and perhaps even an unnecessary therapeutic target, especially in
      advanced malignancies.

PMID- 18344681
TI  - A cyclic chimeric interferon-alpha2b peptide induces apoptosis in tumor cells.
AB  - Interferons alpha (IFNsalpha) are a family of related proteins exhibiting
      antiviral, antiproliferative and immunoregulatory activities. Although IFNsalpha
      have been widely employed for the pharmacological treatment of different types of
      cancer, the therapeutic efficacy occasionally can be diminished by the appearance
      of side effects, neutralizing antibodies or tumor resistance. In the search of
      mimetic peptides of the IFN-alpha2b molecule, we have recently synthesized a
      chimeric cyclic peptide that inhibits IFN-alpha2b binding to its receptor and
      exerts an IFN-like antiproliferative activity. In order to study the mechanism of
      growth inhibition of the cyclic chimera, we evaluated its ability to induce cell
      cycle arrest or apoptosis in WISH cells. We found that the chimeric peptide did
      not cause a cell cycle arrest, although the entire IFN-alpha2b molecule did
      modify cell cycle by increasing the number of S-phase cells. In spite of this
      difference, both molecules were able to induce apoptosis through the activation
      of caspases 8 and 9, indicating the involvement of death receptor and
      mitochondrial pathways. In addition, both peptidic derivative and IFN-alpha2b
      altered the expression of Bcl-2 family proteins and induced the release of
      cytochrome C to cytosol, supporting the participation of mitochondrial pathway in
      the induction of apoptosis. In conclusion, we demonstrated that the chimeric
      cyclic peptide behaved as a potent inducer of apoptosis and it could be a
      potentially useful agent for the treatment of certain malignancies.

PMID- 18344682
TI  - Alteration of glyoxalase genes expression in response to testosterone in LNCaP
      and PC3 human prostate cancer cells.
AB  - Glyoxalase system, a ubiquitous detoxification pathway protecting against
      cellular damage caused by potent cytotoxic metabolites, is involved in the
      regulation of cellular growth. Aberrations in the expression of glyoxalase genes
      in several human cancers have been reported. Recently, we described a possible
      regulatory effect by estrogens on glyoxalase genes in human breast cancer cell
      lines. This result, along with those ones regarding changes in glyoxalases
      activity and expression in other human hormone-regulated cancers, such as
      prostate cancer, has prompted us to investigate whether also androgens, whose
      functional role in prostate cancer pathogenesis is well known, could modulate
      glyoxalases gene expression. Therefore, we treated LNCaP androgen-responsive and
      PC3 androgen-independent human prostate cancer cell lines with testosterone at
      the concentrations of 1 nM and 100 nM. After a two days treatment, glyoxalases
      mRNA levels as well as cell proliferation were evaluated by real-time RT-PCR
      analysis and [3H]thymidine incorporation, respectively. Results pointed out that
      testosterone affects the expression of glyoxalase system genes and cell
      proliferation in a different manner in the two cell lines. The possibility that
      modulation of glyoxalase genes expression by testosterone is due to glyoxalases
      mediated intracellular response mechanisms to the androgen-induced oxidative
      stress or to the presence of androgen response elements (ARE) in glyoxalase
      promoters are discussed. Knowledge regarding the regulation of glyoxalases by
      testosterone may provide insights into the importance of these enzymes in human
      prostate carcinomas in vivo.

PMID- 18344683
TI  - Synergy of Pancratistatin and Tamoxifen in inducing apoptosis in breast cancer
      cells.

PMID- 18344684
TI  - A new trick for an old drug: mTOR inhibitor rapamycin augments the effect of
      fluorouracil on hepatocellular carcinoma by inducing cell senescence.

PMID- 18344686
TI  - Functions of p21 and p27 in the regenerating epithelial linings of the mouse
      small and large intestine.
AB  - The epithelial linings of the small and large intestine are rapidly turned over
      and provide an ideal system for exploring links between differentiation and
      regulation of cell cycle exit. We utilized wild type, p21-/-, p27-/- and p21/p27
      /- mice to address contributions of the Cdk inhibitors p21 and p27 to
      proliferation and differentiation in the mouse gastrointestinal tract. We did not
      detect any significant differences in proliferation, and all differentiated
      epithelial cell lineages were represented in all four genotypes. These data
      indicate that p21 and p27 do not play essential roles in the regulation of normal
      epithelial renewal in the intestine. These Cdk inhibitors are not needed in vivo
      for either assembly of Cdk/Cyclin complexes that drive active proliferation, or
      inhibition of Cdk/Cyclin complexes during cell cycle exit. However, expression of
      Cyclin D2 and to a lesser degree Cyclin D3 was reduced in p27-/- and p21/p27-/-
      mice, indicating a unique role for p27 in the regulation of these specific D-type
      Cyclins in vivo. In the absence of p27, reduced levels of Cyclin D2 and D3 may
      help to counteract increased proproliferative signals in the intestine.

PMID- 18344687
TI  - Pancreatic cancer associated fibroblasts display normal allelotypes.
AB  - BACKGROUND: Recent studies have reported widespread copy number alterations and
      p53 mutations arising in cancer associated stromal cells. The aim of this study
      was to determine if pancreatic cancer associated fibroblasts display similar
      genetic alterations. DESIGN: Cancer-associated fibroblast cultures were
      established from 7 primary pancreatic adenocarcinomas. These fibroblasts and
      corresponding normal tissues when available were analyzed for genome-wide copy
      number changes using Affymetrix 250K SNP microarrays. Evidence of p53 protein
      expression, an indicator of p53 mutation was determined by immunohistochemical
      labeling of tissue microarrays containing 117 pancreatic ductal adenocarcinomas.
      RESULTS: Pancreatic cancer associated fibroblasts did not show any evidence of
      somatic copy number gains or losses. p53 protein expression was confined to
      invasive pancreatic adenocarcinoma cells and was not expressed in cancer
      associated fibroblasts. CONCLUSIONS: We find no evidence that pancreatic cancer
      associated fibroblasts harbor somatic copy number changes or immunohistochemical
      evidence of p53 mutations.

PMID- 18344688
TI  - The let-7 microRNA reduces tumor growth in mouse models of lung cancer.
AB  - MicroRNAs have been increasingly implicated in human cancer and interest has
      grown about the potential to use microRNAs to combat cancer. Lung cancer is the
      most prevalent form of cancer worldwide and lacks effective therapies. Here we
      have used both in vitro and in vivo approaches to show that the let-7 microRNA
      directly represses cancer growth in the lung. We find that let-7 inhibits the
      growth of multiple human lung cancer cell lines in culture, as well as the growth
      of lung cancer cell xenografts in immunodeficient mice. Using an established
      orthotopic mouse lung cancer model, we show that intranasal let-7 administration
      reduces tumor formation in vivo in the lungs of animals expressing a G12D
      activating mutation for the K-ras oncogene. These findings provide direct
      evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that
      this miRNA may be useful as a novel therapeutic agent in lung cancer.

PMID- 18344689
TI  - Predictors of left ventricular thrombus formation in acute myocardial infarction
      treated with successful primary angioplasty with stenting.
AB  - BACKGROUND: There are limited data referring to the incidence of left ventricle
      (LV) thrombus formation after successful primary percutaneous coronary
      intervention (PCI) with stenting, which is now the treatment of choice in
      patients with acute myocardial infarction (AMI). Previously reported results were
      often based on low or heterogeneous patient populations. METHODS: To evaluate the
      prevalence of LV thrombus in the early period of AMI, 2,911 patients who had
      undergone successful primary stenting were retrospectively studied. Baseline
      demographic characteristics, angiographic findings, and antiplatelet treatment
      were analyzed to find predictors of thrombus formation. LV thrombus was diagnosed
      by 2-dimensional echocardiography within 3 to 5 days after PCI. RESULTS: This
      complication was detected in 73 patients (2.5%). Patients with thrombus and
      patients without it were at the same age and had diabetes mellitus, prior
      myocardial infarction, and lipid disorders at the same frequency. The extent of
      coronary artery disease was similar in both groups. The incidence of LV thrombi
      was similar in patients treated with and without glycoprotein IIb/IIIa inhibitors
      (2.02% vs 2.9%, NS). According to results of multiple log-regression analysis,
      the presence of LV thrombus was strongly associated with anterior AMI, ejection
      fraction <40%, and previous hypertension. CONCLUSIONS: The incidence of left
      ventricular thrombus early after AMI is very low if primary PCI with stenting is
      successful, probably due to the salvage of myocardium at risk. Localization of
      AMI and the size of myocardium damage remain the most important independent
      predictors of LV thrombus formation irrespective of various treatments.

PMID- 18344690
TI  - Angiotensin converting enzyme inhibition enhances collateral artery remodeling in
      rats with femoral artery occlusion.
AB  - Evidence from experimental animal studies indicate that ACE inhibition expands
      collateral blood flow both in ischemic hearts and peripheral limbs. The present
      study evaluates whether ACE inhibitor induces collateral blood flow expansion and
      change of angiogenic gene expression profile in collateral arteries during
      remodeling. Male Sprague-Dawley rats, weighing 350 g were treated with vehicle
      (control) or quinapril (ACE inhibitor) at either low dose (3.0 mg/kg) or high
      dose (18 mg/kg) for 1, 3, 7, 14 days (gene expression) or 16 days (blood flow).
      All rats received bilateral occlusions of the femoral arteries. Collateral blood
      flow to the hind limb was assessed by 85Sr and 141Ce-labeled microspheres during
      treadmill running at 15 and 25 m/min speeds. Quinapril reduced plasma ACE
      activity by 58% and 88% for the low-dose and high-dose groups, respectively (P <
      0.001). High-dose quinapril reduced exercising blood pressure (P < 0.05) and
      increased hind limb conductance. Collateral blood flows to calf muscles were 51
      +/- 3.7, 73 +/- 5.0, and 68 +/- 1.9 mL/min per 100 g in control and quinapril low
      and high-dose groups, respectively, during high-speed running (P < 0.001). Real
      time RT-PCR revealed that ACE inhibition shifted gene expression to a
      proangiogenic phenotype in the newly developed collateral arteries. Our findings
      indicate that ACE inhibition could increase collateral-dependent blood flow and
      collateral vessel remodeling by promoting proangiogenic gene expression in newly
      developed collateral arteries. Our results support the potential utility of ACE
      inhibitor as a therapeutic agent in treating peripheral occlusive arterial
      disease.

PMID- 18344691
TI  - Article and journal impact factor in various scientific fields.
AB  - BACKGROUND: We tried to provide the scientific community with data to answer the
      following simple question: What proportion of publications in the various
      scientific fields is published in journals with impact factor above the median
      and mean values of the distribution of journal impact factor? METHODS: We
      analyzed and compared the distribution of the impact factor data reduced to the
      unit of science publication, the article. We calculated the proportion of
      articles published in journals with impact factor above the journal mean impact
      factor, journal median impact factor, and article mean impact. RESULTS: For all
      categories examined, at the article level, the mean impact factor was higher than
      the median (by 13.7% to 500% for the various scientific categories). The mean
      impact factor of journals was considerably lower than the mean impact factor of
      articles (by 0.3 to 6.4 units). The proportion of articles that were published in
      journals with impact factor above the journals' median impact factor was well
      above 50% in 17 of 19 scientific fields examined (all except mathematics and
      computer science). SIGNIFICANCE: Our analysis shows that in most scientific
      fields examined, it is quite easier to publish an article in the top 50% of
      journals (based on impact factor calculations) than it is for the article to be
      included in the top 50% of published articles (based on the assumption made
      regarding the article' impact factor).

PMID- 18344692
TI  - Pneumocystis jiroveci pneumonia in patients with AIDS in the inner city: a
      persistent and deadly opportunistic infection.
AB  - Highly active antiretroviral therapy (HAART) has decreased the morbidity and
      mortality of opportunistic infections including Pneumocystis jiroveci pneumonia
      (PCP) among HIV-infected individuals. We performed a hospital-based retrospective
      cohort study among a population of medically underserved inner city persons
      living in Atlanta, Georgia, diagnosed with confirmed PCP to compare the
      epidemiology and outcomes of PCP during 2 defined periods: 1990 to 1995, or pre
      HAART period, and 1996 to 2001, or HAART period. A total of 488 patients were
      available for analysis. The overall mortality rate was 47% during the pre-HAART
      era compared with 37% during the HAART era (P = 0.02). However, among those
      patients that required medical intensive care unit admission and mechanical
      ventilation, the mortality rate was particularly high, with over 80% of patients
      dying as a result of their episode of PCP during both periods. PCP was the
      initial presentation of HIV infection in 39.3% in the pre-HAART period with a
      mortality rate of 52%, in contrast with 37% in the HAART period, with a mortality
      rate of 45%, respectively (P = NS). Only 30.7% in the pre-HAART period and 31.1%
      of patients in the HAART period were receiving PCP prophylaxis. The overall risk
      of death, when we combined both groups in the analysis, was higher for those
      patients who did not take PCP prophylaxis, those who smoked tobacco, and those
      who were admitted to the medical intensive care unit and required mechanical
      ventilatory support. Our findings suggest that despite the availability of HAART,
      PCP continues to cause a significant burden of disease among inner-city HIV
      infected populations.

PMID- 18344693
TI  - Relations of exercise, self-appraisal, mood changes and weight loss in obese
      women: testing propositions based on Baker and Brownell's (2000) model.
AB  - BACKGROUND: Obesity is a prominent modifiable health risk factor. Treatments of
      severe caloric restrictions and educational interventions have had minimal
      sustained effects on weight loss. Physical activity may have significant indirect
      effects on weight reduction associated with changes in psychological variables,
      although explanatory models are lacking. METHODS: Relationships based on Baker
      and Brownell's model of exercise, self-appraisal, mood change, and weight loss
      were tested with obese (body mass index > or =30) women initiating a supported
      exercise and nutrition information program over 6 months. RESULTS: Exercise
      participation was associated with significant improvements in mood, body image,
      and exercise-related self-efficacy. When changes on measures of these factors
      were simultaneously entered into a multiple regression equation, a significant
      portion of the variance in exercise session attendance was accounted for (R2 =
      0.26, F(7, 52) = 2.57, P < 0.05), with changes in tension (beta = -0.34) and
      physical self-concept (beta = 0.33) making significant unique contributions.
      Exercise session attendance was significantly correlated with weight and body
      composition changes (r = -0.30 to -0.47). The indirect effect of exercise on
      weight loss was estimated at 0.23. As hypothesized, less improvement in
      depression was significantly associated with less improvement in weight and body
      composition (r values = 0.23 to 0.29). CONCLUSIONS: Physical activity and
      exercise may have positive effects on sustained weight loss due to associated
      changes in self-appraisal and mood factors. Early incorporation of moderate
      exercise into weight management treatments may have considerable value beyond
      just energy expenditure. Continued testing of explanatory models is warranted.

PMID- 18344694
TI  - A 70-year-old woman with abdominal pain.

PMID- 18344695
TI  - The salt-avid state of congestive heart failure revisited.
AB  - Congestive heart failure (CHF), a clinical syndrome, comprises a constellation of
      signs and symptoms whose origins are rooted in a salt-avid state mediated largely
      by effector hormones of the renin-angiotensin-aldosterone system (RAAS). Stimuli
      that normally lead to an activation of this circulating neurohormonal system
      include reduced dietary sodium, upright posture with or without exercise, and
      thermal stress. These stimuli remain operative in patients with heart failure;
      however, here renal perfusion is reduced, leading to excessive RAAS activation.
      This can contribute to an inability to adequately excrete dietary sodium (salt
      sensitivity). Active Na+ and water retention (salt avidity) account for an
      initial expansion of intravascular volume and subsequent rise in extravascular
      volume. Neurohormonal regulation of Na+ excretion therefore is the
      pathophysiologic basis for clinical decompensation and the appearance of CHF. By
      contrast, and despite comparable levels of heart failure, expressed as diastolic
      or systolic ventricular dysfunction, patients in whom circulating RAAS hormones
      remain normal are clinically compensated without CHF. Interventions, such as
      regulated dietary Na+, prolonged bed rest, intermittent periods of semirecumbency
      (with legs up), water immersion, thermal neutrality, and pharmacologic
      interference with the generation and activity of RAAS hormones, can be used to
      attenuate the salt avidity found in patients with CHF.

PMID- 18344696
TI  - Optimizing therapy with allopurinol: factors limiting hypouricemic efficacy.
AB  - The aim of this review is to examine clinical aspects of the use of the
      hypouricemic drug allopurinol. Allopurinol is a moderately active hypouricemic
      drug. Its activity is largely the result of the inhibition of xanthine
      oxidoreductase by oxypurinol, the active metabolite of allopurinol. The activity
      of allopurinol may be limited by oxypurinol, reducing the renal clearance of
      urate. Optimal use of allopurinol involves individualization of dose to attain a
      sufficient decrease in plasma urate concentrations. This may require a dose
      greater than recommended based on creatinine clearance. The initial use of an
      anti-inflammatory drug or low-dose colchicine decreases but does not eliminate
      the development of acute attacks of gout during the initiation of therapy with
      allopurinol. Monitoring of oxypurinol concentrations has shed some light on the
      efficacy of allopurinol but more data are required particularly in patients with
      renal impairment. Probenecid increases the hypouricemic effect of allopurinol but
      the favorable interaction may be significant only in patients with glomerular
      filtration rates greater than about 50 mL/min.

PMID- 18344697
TI  - Adenosine deaminase in the diagnosis of tuberculous pericardial effusion.
AB  - Not long ago, primary tuberculosis was considered a rare disease; now with an
      increasing incidence worldwide, physicians should relearn many of its basic
      aspects and manifestations. Pericarditis is a rare finding seen with
      tuberculosis, but its prognosis is excellent with treatment, so early diagnosis
      is crucial. Pathogenesis is particularly important, and it must be taken in
      consideration when interpreting diagnostic tools. Herein we report on a healthy
      32-year-old woman who presents with a 1-month history of febrile illness,
      malaise, and weakness; more recently, she also had resting dyspnea, which was
      progressively worsening. A positive PPD and an abnormal chest radiograph prompted
      hospitalization, where she was found to have pulsus paradoxus of 20 mm Hg. The
      echocardiogram showed diastolic right chamber collapse along with respiratory
      variation of the mitral inflow, consistent with pericardial tamponade. A
      pericardiocentesis was performed with resolution of her resting dyspnea; more
      than 1000 mL of serous fluid drained from the pericardial space over the
      following 24 hours. Although sputum and pericardial fluid cultures and smear for
      AFB and other organisms were negative, as well as a negative pericardial fluid
      PCR for Mycobacterium tuberculosis DNA; an elevated (44.4 U/L [normal, 0 to 18])
      adenosine deaminase level in the pericardial fluid was consistent with the
      probable diagnosis of tuberculous pericardial effusion. The patient was treated
      with resolution of the clinical syndrome and no recurrence of the effusion
      thereafter. Adenosine deaminase, an enzyme marker of cell-mediated immune
      response activity to M tuberculosis that includes activated T-lymphocytes and
      macrophages, appears in pericardial fluid. The diagnosis of probable tuberculous
      effusion can be made without demonstration of mycobacterium.

PMID- 18344698
TI  - Thrombotic thrombocytopenic purpura associated with Brucella infection.
AB  - Thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated
      thrombotic occlusions located in the microcirculation and a syndrome of
      microangiopathic hemolytic anemia (MAHA), thrombocytopenia, fever, and renal and
      neurologic abnormalities. Although several factors such as viral and bacterial
      pathogens, pancreatitis, drugs, collagen-vascular diseases, cancers, and
      pregnancy have been reported to be associated with TTP, brucellosis is an
      exceptional cause of this disorder. We represent a 19-year-old woman applying to
      our outpatient department with the complaints of headache, fever, sweat, malaise,
      and jaundice. Clinical signs and laboratory findings were consistent with TTP.
      Brucella agglutination was found to be 1/320 positive. After the administration
      of therapeutic plasma exchange, all symptoms and laboratory abnormalities
      improved dramatically. Antibiotic therapy directed to Brucella infection was
      initiated and no recurrence of TTP was seen.

PMID- 18344699
TI  - A 71-year-old man with unilateral wheezing: an unusual cause.
AB  - We present an unusual case of a 71-year-old man with unilateral wheezing brought
      on by change in position. Isolated bronchomalacia in the absence of tracheal
      involvement occurs more commonly in children and in adults with emphysema,
      chronic bronchitis, extrinsic compression by tumors, compression by abnormal
      blood vessels or vascular rings, relapsing polychondritis, endotracheal
      intubation and mechanical ventilation, enlarged left atrium, trauma, and lung
      transplantation. Our patient had predominant unilateral bronchomalacia. In this
      report, we present the clinical features, review the literature, and describe the
      probable pathophysiology.

PMID- 18344700
TI  - Systemic vasculitis with gastrointestinal involvement in an HIV-infected adult.
AB  - Several types of human immunodeficiency virus (HIV)-associated vasculitides,
      including polyarteritis nodosa-like syndromes have been reported in patients with
      HIV infection. The pathogenic mechanism is thought to be related to either
      circulating immune complexes or direct endothelial involvement by HIV per se. In
      HIV-related necrotizing systemic vasculitis, affected arteries are smaller than
      those seen in classic polyarteritis nodosa, and it rarely becomes a multisystem
      and life-threatening disease with the exception of cases with heart, kidney,
      central nervous system, or gut involvement. We describe a case of systemic
      necrotizing vasculitis in an HIV-infected individual presented with fever,
      purpuric rash, and polyarthritis who eventually had development of mesentery
      artery thrombosis and nephrotic syndrome. The patient, solely under triple
      antiretroviral therapy, remains symptom free, with no evidence of his multisystem
      disease and no progression of his HIV infection after 10 years of follow-up. All
      patients with a vasculitis of unidentified etiology should be evaluated for HIV
      infection.

PMID- 18344701
TI  - Thoracic chordoma: an unusual presentation of the spinal tumor.
AB  - Chordoma is an uncommon malignant bone tumor that originates from the remnants of
      the embryonic notochord. In most of the reported cases, chordomas occur at the
      skull base or in the sacrococcygeal spine but rarely in the thoracic spine. In
      this report, we describe a case of a large thoracic chordoma with posterior
      mediastinal extension in a 25-year-old woman who presented with left-hand
      anhydrosis. The imaging studies, pathology findings, and recent advances in
      treatment are discussed.

PMID- 18344702
TI  - Ultrasound imaging of fasciitis due to body-building supplement.
AB  - BACKGROUND: Fascia and soft tissues, rich in collagen, receptors of pain and
      capable of significant distention, may be targets of autoimmune inflammatory
      diseases. We observed fasciitis due to the protein supplement Pure Whey, which
      has not been reported previously. METHODS: Sonography (Sonosite-Titan, 5 to 10
      MHz, L-38) was performed on a patient (age, 26 years; body mass index, 38 kg/m2)
      with protein fasciitis. He had developed compact swelling of his forearms, hands,
      and legs, with skin irregularity and severe disability (without peripheral
      eosinophilia, normal Ig and ESR 18/hr) after taking Pure Whey, containing L
      tryptophan (1.4 g per 100 g of protein). A deep skin biopsy was performed. The
      thickness of the brachioradial fascia (BRF) was measured and compared with 10
      healthy control subjects (men ages 36.7 +/- 8.3 years; body mass index, 26.4 +/-
      6.5 kg/m2). RESULTS: The deep skin biopsy showed severe fat interlobular and
      fascial thickening with mononuclear (noneosinophilic) infiltrate and fibrosis
      associated with fasciitis. BRF of the 10 healthy men had a thickness of 0.75 +/-
      0.19 mm, compared with the patient's 2.4 mm thickened and cleaved BRF. After 2.5
      months of corticosteroid therapy (30 mg/d with tapering) and discontinuation of
      the protein supplement, the patient's BRF returned to a monolayer appearance. Its
      thickness reduced to normal (0.8 mm), with significant clinical improvement.
      CONCLUSIONS: This case of noneosinophilic fasciitis associated with ingestion of
      L-tryptophan-containing protein supplement responded favorably to corticosteroid
      therapy. Sonography proved to be an effective method to visualize and confirm the
      fasciitis and to follow the course and therapy.

PMID- 18344703
TI  - A rare and unusual cause of PSA (prostate-specific antigen) elevation:
      sarcoidosis of the prostate.
AB  - Sarcoidosis and prostate cancer are 2 separate conditions that are more prevalent
      among the African American population. However, sarcoidosis of the prostate is a
      very rare clinical entity. Its association with prostate cancer is described in
      clinical case series. The use of PSA (prostate specific antigen) test for
      screening prostate cancer may be associated with false-positive results in this
      patient population. We report a patient who had an elevated PSA but had a biopsy
      proven to be sarcoidosis of the prostate gland.

PMID- 18344704
TI  - Uptake and timing of bilateral prophylactic salpingo-oophorectomy among BRCA1 and
      BRCA2 mutation carriers.
AB  - PURPOSE: To evaluate prophylactic salpingo-oophorectomy uptake and timing among
      BRCA1/2 mutation carriers in a cancer risk assessment program. METHODS: Clinical
      records of female BRCA1/2 mutation carriers who received cancer genetic
      counseling between 1996 and 2003 were reviewed to determine the completion and
      the timing of prophylactic salpingo-oophorectomy. Logistic regression models
      evaluated associations between subject characteristics and surgery. Survival
      analysis methods were used to estimate the distribution of time to surgery.
      RESULTS: Among 88 women, 70% underwent prophylactic salpingo-oophorectomy.
      Prophylactic salpingo-oophorectomy was associated with older age, white race,
      having children, and a family history of ovarian cancer. Many women waited more
      than 12 months to undergo surgery and some delayed by several years. Younger age
      and not having children were associated with delays to surgery. CONCLUSION:
      Prophylactic salpingo-ooporectomy is an acceptable risk reduction measure for
      many BRCA1/2 mutation carriers. Some women make this decision many years after
      genetic testing. Continued discussion of the risks and benefits of risk reduction
      options may facilitate the uptake of recommended risk reduction interventions
      among BRCA mutation carriers.

PMID- 18344705
TI  - Increased genetic counseling support improves communication of genetic
      information in families.
AB  - PURPOSE: To determine whether the provision of additional genetic counseling
      support could improve the uptake of genetic services by "at-risk" relatives of
      probands. METHODS: The Tasmanian Clinical Genetics Service implemented a specific
      counseling intervention to a cohort of patients who were diagnosed with a genetic
      condition with familial implications and compared this with a control cohort who
      had not experienced the specific counseling intervention. The study involved 150
      family members in 19 different kindreds across the two cohorts. The principal
      outcome measure was the proportion of at-risk relatives who had made contact with
      the clinical genetics service within 2 years of the diagnosis in the index
      patient. RESULTS: The proportion of at-risk relatives who made contact with the
      genetics service was 61% in the intervention cohort compared with 36% in the
      control cohort (P = 0.01). After controlling for the gender of the at-risk
      relatives, relatives in the intervention cohort were 2.6 times more likely to
      make contact with the genetics service (P = 0.02). CONCLUSIONS: The provision of
      increased genetic counseling support significantly increased the proportion of at
      risk relatives who made contact with the genetic service. This suggests that the
      communication of genetic information within families can be enhanced by the
      provision of increased genetic counseling support.

PMID- 18344706
TI  - Ethnicity, sex, and the incidence of congenital heart defects: a report from the
      National Down Syndrome Project.
AB  - PURPOSE: The population-based National Down Syndrome Project combined
      epidemiological and molecular methods to study congenital heart defects in Down
      syndrome. METHODS: Between 2000 and 2004, six sites collected DNA, clinical, and
      epidemiological information on parents and infants. We used logistic regression
      to examine factors associated with the most common Down syndrome-associated heart
      defects. RESULTS: Of 1469 eligible infants, major cardiac defects were present in
      44%; atrioventricular septal defect (39%), secundum atrial septal defect (42%),
      ventricular septal defect (43%), and tetralogy of Fallot (6%). Atrioventricular
      septal defects showed the most significant sex and ethnic differences with twice
      as many affected females (odds ratio, 1.93; 95% confidence interval, 1.40-2.67)
      and, compared with whites, twice as many blacks (odds ratio, 2.06; 95% confidence
      interval, 1.32-3.21) and half as many Hispanics (odds ratio, 0.48; 95% confidence
      interval, 0.30-0.77). No associations were found with origin of the
      nondisjunction error or with the presence of gastrointestinal defects.
      CONCLUSIONS: Sex and ethnic differences exist for atrioventricular septal defects
      in Down syndrome. Identification of genetic and environmental risk factors
      associated with these differences is essential to our understanding of the
      etiology of congenital heart defects.

PMID- 18344707
TI  - How physicians use array comparative genomic hybridization results to guide
      patient management in children with developmental delay.
AB  - PURPOSE: Array comparative genomic hybridization is an emerging test used
      clinically to identify the etiology of children with developmental delay, yet
      little data are available regarding how physicians use these results. This pilot
      study evaluated how positive test results were used to influence patient
      management. METHODS: We surveyed 14 physicians of 48 patients who had copy number
      changes detected by microarray technology. RESULTS: Of 48 patients, 34 (70.8%)
      had 65 management changes after receiving the test result (with individual
      patients having 1-3 changes). Most commonly, physicians provided patients'
      families with a recurrence risk for affected subsequent pregnancies (35% of
      patients). Patients avoided other forms of testing (35%) and had improved access
      to services (25%). In 27% of patients, physicians altered medical management by
      referring patients to a specialist or recommending medical screening. Patients
      with known syndromes had multiple changes, but patients with novel copy number
      changes also had recommendations made based on the array result. CONCLUSIONS:
      Overall, physicians reported making changes in management among most patients
      with positive test results, in ways similar to abnormalities detected by
      conventional cytogenetics. Our study demonstrates that this testing, in our
      clinical setting, is affecting management of children with developmental delay.

PMID- 18344708
TI  - Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in
      the Han population.
AB  - PURPOSE: To determine whether the main mitochondrial DNA (mtDNA) haplogroups of
      the Han people have an impact on long-term clinical outcome. METHODS: We
      prospectively studied 181 individuals who were sequentially admitted to the
      intensive care unit. Demographic and clinical data were recorded along with
      clinical outcome over 180 days. Follow-up was completed for all study
      participants. We then determined the mtDNA haplogroups of the patients and 570
      healthy, age-matched Han people from Zhejiang province, Southeast China, by
      analyzing sequences of hypervariable mtDNA segments and testing diagnostic
      polymorphisms in the mtDNA coding region with DNA probes. RESULT: The frequency
      of the main subhaplogroups of the Han population in the study cohort did not
      differ significantly from the control group. mtDNA haplogroup R, one of the three
      main mtDNA haplogroups of the Han people, was a strong independent predictor for
      the outcome of severe sepsis, conferring a 4.68-fold (95% CI 1.903-10.844, P =
      0.001) increased chance of survival at 180 days compared with those without the
      haplogroup R. CONCLUSION: In the Han population, mtDNA haplogroup R was a strong
      independent predictor for the outcome of severe sepsis, conferring an increased
      chance of long-term survival compared with individuals without the R haplogroup.

PMID- 18344709
TI  - Great expectations: views of genetic research participants regarding current and
      future genetic studies.
AB  - PURPOSE: Recruitment of prior participants in genetic research is one strategy
      suggested to maximize efficient use of research dollars in gene-environment
      studies. We explored attitudes toward genetic research participation among people
      in a case-control genetic epidemiology study of colon cancer, the North Carolina
      Colorectal Cancer Study (NCCCS). METHODS: Quantitative and qualitative cross
      sectional analysis of 801 NCCCS participants. RESULTS: Participants were "very
      positive" (63%) or "positive" (32%) about genetic research, and "very likely"
      (49%) or "somewhat likely" (40%) to participate in future genetic research.
      Variables significantly associated with feeling "very positive" were white race,
      more education, nonreligious, hearing "a lot" about genetic research, and two
      measures of trust in medical research. Except for race and education, the same
      variables were significantly associated with being "very likely" to participate
      in future studies. Qualitatively, "good things" for self and family included
      discovering causes and cures for cancer, and the value of genetic information.
      Many could not list "bad things"; those who did mentioned anxiety, "knowing too
      much," losing confidentiality, or abuse of information. CONCLUSIONS: Despite very
      positive attitudes of these participants toward genetic research, there is
      significant variation based on participant characteristics. These findings should
      encourage and caution researchers attempting to recruit prior participants into
      genetic studies.

PMID- 18344710
TI  - Distribution of CFTR mutations in Saguenay- Lac-Saint-Jean: proposal of a panel
      of mutations for population screening.
AB  - PURPOSE: Saguenay-Lac-Saint-Jean is a region located in the northeastern part of
      the Province of Quebec, Canada, and is characterized by a founder effect. In this
      region, it has been documented that the incidence of cystic fibrosis reached
      1/902 live births between 1975 and 1988, three times higher than the average
      incidence of 1/2500 live births reported in other Caucasian populations. This
      corresponds to a carrier rate of 1/15. METHODS: Using genotyping data from the
      Canadian Consortium for Cystic Fibrosis Genetic Studies, this article describes
      the cystic fibrosis transmembrane conductance regulator profile of the cystic
      fibrosis population living in the Saguenay-Lac-Saint-Jean region and compares it
      with cystic fibrosis populations living in three other regions of the Province of
      Quebec. RESULTS: Significant differences in allelic frequencies of common
      mutations (as DeltaF508, 621 + 1G>T and A455E), and in percentage of covered
      allele with three or six mutations, were found in Saguenay-Lac-Saint-Jean
      compared to other regions. Based on this result, two mutation panels exceeding
      90% sensitivity threshold are now proposed for cystic fibrosis carrier screening
      in this region. CONCLUSION: The implementation of the proposed carrier screening
      program could diminish the incidence of this disease in this region and allow
      future parents to make informed decisions about family planning.

PMID- 18344712
TI  - IL-1beta (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)
      infected patients on highly active antiretroviral treatment (HAART) against
      lipodystrophic syndrome.
AB  - PURPOSE: To evaluate the impact of acquired and inherited factors on the
      development of lipodystrophic syndrome in patients on highly active
      antiretroviral therapy. METHODS: Two hundred forty-three human immunodeficiency
      virus-infected Caucasians on highly active antiretroviral therapy were
      prospectively followed-up for 3 years. Eleven were naIve and 232 were on
      antiretrovirals (mean, 93.0 months +/- 43.8 months). Lipodystrophic syndrome was
      diagnosed clinically with a lipodystrophy severity grading scale. Polymorphisms
      of cytokines (IL-1beta, IL-6, TNF-alpha), TLR4, and NOS genes were genotyped.
      RESULTS: Ninety (37%) patients developed lipodystrophic syndrome. The polymorphic
      T allele of the (+3954C/T) polymorphism of IL-1beta was less frequent in patients
      with lipodystrophic syndrome compared with those without (17.8% vs. 27.0%, P =
      0.03). Factors significantly associated with lipodystrophic syndrome were time on
      stavudine (P < 0.001), use of stavudine (P = 0.001), absence of the T allele of
      the (+3954C/T) IL-1beta polymorphism (P = 0.02), acquired immune deficiency
      syndrome diagnosis (P = 0.005), nadir levels of CD4 (P = 0.003), and time on
      highly active antiretroviral therapy (P = 0.003). Of these factors, only the time
      on stavudine (hazard ratio [95% confidence intervals] 1.007 [1.001-1.013]), use
      of stavudine (1.678 [1.048-2.68]), and absence of the T allele of the IL-1beta
      (+3954C/T) polymorphism (0.569 [0.347-0.931]) were significantly associated with
      lipodystrophic syndrome by Cox regression. CONCLUSIONS: Genotyping of the
      (+3954C/T) polymorphism of IL-1beta could be useful in patients starting highly
      active antiretroviral therapy, especially in potential users of stavudine, to
      predict their risk of developing lipodystrophic syndrome.

PMID- 18344713
TI  - Parathyroid hormone reserve in 22q11.2 deletion syndrome.
AB  - OBJECTIVE: We hypothesized that most patients with 22q11.2 deletion and a history
      of hypocalcemia have inadequate parathyroid function, manifested by intact
      parathyroid hormone levels below normal. We aimed to evaluate intact parathyroid
      hormone levels both during normocalcemia and at hypocalcemia, in this population.
      STUDY DESIGN: Retrospective chart review of 103 patients with 22q11.2 deletion
      born since 1997 and cared for at the Children's Hospital of Philadelphia. Calcium
      and intact parathyroid hormone drawn simultaneously were recorded, along with
      clinical presentation at hypocalcemia. RESULTS: Forty-seven simultaneous
      Ca/intact parathyroid hormone values were available. Seventy-nine percent of
      calcium levels and 81% of parathyroid hormone levels were within normal range.
      There were 19 patients with a history of symptomatic hypocalcemia, for whom any
      available simultaneous Ca/parathyroid hormone levels, before, during, or after
      hypocalcemia were analyzed. In this subgroup, 59% of calcium and 76% of
      parathyroid hormone levels were normal. None had an intact parathyroid hormone of
      >39.2 pg/mL at hypocalcemia. Seventy-three percent of hypocalcemic events had a
      precipitating stressor. CONCLUSIONS: Hypoparathyroidism in 22q11.2 deletion is
      mild, manifesting as a phenomenon of decreased parathyroid hormone reserve.
      Subjects are normocalcemic most of the time, but are unable to mount elevated
      intact parathyroid hormone levels, and therefore unable to correct hypocalcemia,
      in response to stressors.

PMID- 18344711
TI  - Incorporating ethnicity into genetic risk assessment for Alzheimer disease: the
      REVEAL study experience.
AB  - PURPOSE: To describe how investigators in a multisite randomized clinical trial
      addressed scientific and ethical issues involved in creating risk models based on
      genetic testing for African American participants. METHODS: The following
      informed our decision whether to stratify risk assessment by ethnicity:
      evaluation of epidemiological data, appraisal of benefits and risks of
      incorporating ethnicity into calculations, and feasibility of creating ethnicity
      specific risk curves. Once the decision was made, risk curves were created based
      on data from a large, diverse study of first-degree relatives of patients with
      Alzheimer disease. RESULTS: Review of epidemiological data suggested notable
      differences in risk between African Americans and whites and that Apolipoprotein
      E genotype predicts risk in both groups. Discussions about the benefits and risks
      of stratified risk assessments reached consensus that estimates based on data
      from whites should not preclude enrolling African Americans, but population
      specific risk curves should be created if feasible. Risk models specific to
      ethnicity, gender, and Apolipoprotein E genotype were subsequently developed for
      the randomized clinical trial that oversampled African Americans. CONCLUSION: The
      Risk Evaluation and Education for Alzheimer Disease study provides an instructive
      example of a process to develop risk assessment protocols that are sensitive to
      the implications of genetic testing for multiple ethnic groups with differing
      levels of risk.

PMID- 18344714
TI  - Limb girdle muscular dystrophy: an interval study of weakness and functional
      impairment.
AB  - OBJECTIVE: Prospective studies of the natural history of a myopathy are effective
      means of measuring the status and progression of disease. This 10-year interval
      study of progressive weakness and functional decline was aimed to document the
      natural course of clinically well-characterized limb girdle muscular dystrophy in
      South Africa. METHODS: The manual muscle test (MMT) was used to evaluate limb
      strength; global strength was measured by the average muscle score (AMS). A
      nonlinear functional grading system was used to measure impairment of the arms
      and legs. An activities of daily living (ADL) scale was used to assess disability
      across multiple functional domains in a home environment. RESULTS: The mean AMS
      deteriorated from 5.9 to 4.9 (on a 10-point scale) and was unrelated to patient
      age and disease duration. Most (78%) patients lost arm function. All patients
      maintained useful hand function. Two thirds of patients lost leg function. Half
      of the patients were wheelchair bound, and they reached this level of function
      around the end of their fourth decade of life. Every patient showed functional
      deterioration on the ADL scale. The mean score worsened from 65.6 to 77.2 (out of
      156 points). The disability change was most pronounced in patients who became
      wheelchair bound. CONCLUSION: This interval analysis showed a significant decline
      of limb strength that was independent of patient age or duration of disease and
      was more rapid in stronger patients. A functional grading system detected decline
      and was a useful measure of deterioration when applied to patients over
      intervals. An ADL assessment ascertained a significant functional decline across
      multiple functional domains in a home environment and allowed us to advise
      patients on compensatory strategies to limit dependence.

PMID- 18344715
TI  - Steroid-responsive myopathy: immune-mediated necrotizing myopathy or polymyositis
      without inflammation?
AB  - OBJECTIVE: To describe the clinical course and steroid responsiveness of a
      patient with subacute proximal symmetric weakness, very high serum creatine
      kinase activity, and myopathic pattern with fibrillations in the electromyogram,
      whose muscle biopsy showed necrotizing myopathy, with practically no
      inflammation. DESIGN: Case report. SETTING: Academic research. RESULTS: Diagnosis
      of muscular dystrophy was suggested; nevertheless, steroid treatment was
      initiated, and the patient recovered and gained normal strength. However, after a
      few years he stopped treatment, and all symptoms recurred. He developed severe
      proximal weakness of all limbs. Another biopsy showed similar findings, with no
      inflammation; still, he responded favorably to steroids and immunosuppressive
      medications. Currently on a low dose of prednisone and methotrexate, he has no
      neurological deficit. CONCLUSION: The absence of inflammation in muscle biopsy
      may lead to misdiagnosis of muscular dystrophy; however, if the clinical
      impression is that of inflammatory myopathy, an immunomodulatory treatment should
      be initiated. During the past century, there has been much controversy about the
      diagnosis of polymyositis (PM). The debate is still ongoing. We present hereby a
      patient with typical course and clinical features of PM who underwent two muscle
      biopsies, several years apart, which showed necrotizing myopathy, practically
      without inflammation, leading to misdiagnosis of muscular dystrophy. This report
      brings up the dispute regarding the role of muscle biopsy in the diagnosis of PM.

PMID- 18344716
TI  - Neuromuscular features in the camera-marugo-cohen syndrome.
AB  - We describe the case of a 24-year-old Japanese man suffering from obesity, mental
      retardation, muscle weakness, camptodactyly, syndactyly, and a urinary tract
      cleft. His muscle weakness, which was slightly distally dominant in the
      extremities, was almost static and showed slow progression for several years. He
      had normal blood chromosomes (46, XY) and showed normal levels of sex hormones. A
      needle electromyographic examination of the upper- and lower-limb muscles
      revealed a reinnervation pattern with large-amplitude, long-duration motor unit
      potentials. A muscle biopsy also showed denervation and reinnervation patterns,
      with small-group atrophy and type grouping, with numerous small, angulated
      fibers. Our findings suggest that these neuromuscular features of the Camera
      Marugo-Cohen syndrome are caused by neurogenic changes rather than myogenic
      changes.

PMID- 18344717
TI  - Isolated head drop triggered by neck surgery following concomitant
      chemoradiotherapy.
AB  - Dropped head syndrome (DHS) is characterized by severe weakness of neck extension
      that occurs in isolation or association with a generalized neuromuscular
      disorder. Multietiologies may be responsible for DHS, including radiotherapy,
      which may cause a delayed form of DHS. However, DHS acutely triggered by neck
      surgery after chemoradiotherapy is rare. The author reports a case of acute onset
      of isolated DHS following selective neck dissection surgery after concomitant
      chemoradiotherapy for laryngeal cancer.

PMID- 18344718
TI  - A comparison of the effectiveness of intravenous immunoglobulin and plasma
      exchange as preoperative therapy of myasthenia gravis.
AB  - OBJECTIVES: Immunomodulation with plasma exchange is effective in preparing
      patients for thymectomy. Newer forms of immunomodulation, such as intravenous
      immunomodulation, require evaluation in this clinical setting. METHODS: We
      conducted a retrospective chart review to determine if plasma exchange and
      intravenous immunoglobulin had comparable effectiveness in the preoperative
      preparation of patients with myasthenia gravis. RESULTS AND CONCLUSIONS: The
      results show that intravenous immunoglobulin may have comparable efficacy in the
      preoperative preparation of patients with myasthenia gravis and that this therapy
      is a reasonable alternative to plasma exchange in this clinical setting.

PMID- 18344720
TI  - Neuromuscular pathology case.

PMID- 18344721
TI  - Beyond the "hype" on the association between metabolic syndrome and atypical
      antipsychotics: the confounding effects of cohort, typical antipsychotics, severe
      mental illness, comedications, and comorbid substance use.

PMID- 18344722
TI  - Dyslipidemia independent of body mass in antipsychotic-treated patients under
      real-life conditions.
AB  - OBJECTIVE: Antipsychotic (AP) treatment, in particular with some second
      generation drugs, is associated with weight gain and other metabolic side
      effects. However, the relationship between drug-induced weight gain and
      dyslipidemia is not well understood. We investigated how cardiometabolic risk
      factors were related to body mass during treatment with different APs under real
      life conditions. METHODS: This cross-sectional naturalistic study included 242
      subjects with severe mental disorders who were on monotherapy with olanzapine
      (OLZ) or clozapine (CLZ) (n = 80), monotherapy with other APs (n = 80), or
      unmedicated (n = 82). Groups were adjusted for age and compared for prevalence of
      the metabolic syndrome and its components. Groups were further adjusted for body
      mass and compared for mean values of blood pressure, lipids, and fasting glucose.
      RESULTS: There was no significant intergroup difference in the prevalence of
      metabolic syndrome, obesity, hypertension, or hyperglycemia. Despite similar body
      mass index, OLZ/CLZ-treated subjects had significantly higher prevalence of
      dyslipidemia (high triglyceride and low HDL cholesterol levels) than unmedicated
      subjects. They also had higher mean values of triglycerides (P = 0.003) and lower
      mean values of HDL cholesterol (P < 0.001). Patients treated with other APs had
      intermediate values. CONCLUSIONS: Intergroup differences in body mass index were
      minimal in this naturalistic setting, probably because of awareness of this
      treatment hazard among clinicians. However, independently of body mass,
      dyslipidemia was significantly associated with AP treatment, in particular with
      OLZ and CLZ. These findings indicate a primary effect of APs on lipid regulation,
      important in understanding their mechanism of action, and with clinical
      implications.

PMID- 18344723
TI  - A preliminary investigation of alpha-lipoic acid treatment of antipsychotic drug
      induced weight gain in patients with schizophrenia.
AB  - Weight gain and other metabolic disturbances have now become discouraging, major
      side effects of atypical antipsychotic drugs (AAPDs). The novel strategies
      required to counteract these serious consequences, however, should avoid
      modulating the activities of the neurotransmitter receptors involved because
      those receptors are the therapeutic targets of AAPDs. Adenosine monophosphate
      activated protein kinase is an enzyme that plays a pivotal role in energy
      homeostasis. We hypothesized that alpha-lipoic acid (ALA), which is known to
      modulate adenosine monophosphate-activated protein kinase activity in the
      hypothalamus and peripheral tissues, would ameliorate AAPD-induced weight gain.
      We describe the case series of a 12-week ALA trial in schizophrenia patients
      treated with AAPDs. Two of 7 enrolled subjects were dropped from the study
      because of noncompliance and demand for new medication to treat depressive
      symptoms, respectively. The mean (SD) weight loss was 3.16 (3.20) kg (P = 0.043,
      last observation carried forward; median, 3.03 kg; range, 0-8.85 kg). On average,
      body mass index showed a significant reduction (P = 0.028) over the 12 weeks.
      During the same period, a statistically significant reduction was also observed
      in total cholesterol levels (P = 0.042), and there was a weak trend toward the
      reduction in insulin resistance (homeostasis model assessment of insulin
      resistance) (P = 0.080). Three subjects reported increased energy subjectively.
      The total scores on the Brief Psychiatric Rating Scale and the Montgomery-Asberg
      Depression Rating Scale did not vary significantly during the study. These
      preliminary data suggest the possibility that ALA can ameliorate the adverse
      metabolic effects induced by AAPDs. To confirm the benefits of ALA, more extended
      study is warranted.

PMID- 18344724
TI  - Efficacy of quetiapine for impulsivity and affective symptoms in borderline
      personality disorder.
AB  - Data on the efficacy of quetiapine in borderline personality disorder (BPD) are
      still scarce. We aimed to investigate the efficacy of quetiapine for impulsivity
      and a broad range of affective symptoms in BPD. In this 12-week open-label study,
      we included individuals with BPD who presented to psychiatric in- and outpatient
      services. After a gradual titration of quetiapine, a flexible dose (range, 100
      800 mg) was administered. The main outcome measures consisted of the scores on
      patient-rated questionnaires (Barratt Impulsiveness Scale, Buss-Durkee Hostility
      Inventory, Affective Lability Scale, Spielberger State and Trait Anxiety
      Inventory, Spielberger State and Trait Anger Inventory, and Beck Depression
      Inventory) and on neurocognitive tasks related to impulsivity (Stroop Color Word
      Task and IOWA Gambling Task). A mixed linear model, correcting for age, sex,
      antidepressant use, and weeks in psychotherapy, was applied. Forty-one patients
      (34 females and 7 males; mean [SD] age, 27.0 [9.0] years) were enrolled in the
      study, 32 of which completed the trial. Patients' scores decreased significantly
      (mean [SD] difference; P value) on the Barratt Impulsiveness Scale (19.7 [2.0]; P
      < 0.0001), Buss-Durkee Hostility Inventory (11.5 [1.4]; P < 0.0001), Affective
      Lability Scale (0.75 [0.08]; P < 0.0001), Beck Depression Inventory (25.0 [1.7];
      P < 0.0001), Spielberger State and Trait Anxiety Inventory state (19.9 [1.9]; P <
      0.0001) and trait (20.8 [1.7]; P < 0.0001) subscale, and Spielberger State and
      Trait Anger Inventory state (7.3 [1.1]; P < 0.0001) and trait (10.1 [1.0]; P <
      0.0001) subscale. In addition, patients showed significantly less inference on
      the Stroop Color Word Task and had more 'good choices' on the IOWA Gambling Task.
      These results suggest that quetiapine may be efficacious in the treatment of
      impulsivity and affective symptoms in BPD.

PMID- 18344725
TI  - The efficacy and safety of aripiprazole as adjunctive therapy in major depressive
      disorder: a second multicenter, randomized, double-blind, placebo-controlled
      study.
AB  - Nonresponse to one or more antidepressants is common and an important public
      health problem. This study evaluated the efficacy and safety of adjunctive
      aripiprazole or placebo to standard antidepressant therapy (ADT) in patients with
      major depressive disorder who showed an inadequate response to at least 1 and up
      to 3 historical and 1 additional prospective ADT. The study comprised a 7-28-day
      screening, an 8-week prospective treatment, and a 6-week randomization phase.
      During prospective treatment, patients experiencing a major depressive episode
      (17-item Hamilton Rating Scale for Depression total score > or = 18) received
      single-blind adjunctive placebo plus clinicians' choice of ADT (escitalopram,
      fluoxetine, paroxetine controlled-release, sertraline, or venlafaxine extended
      release). Subjects with inadequate response were randomized to adjunctive placebo
      (n = 190) or adjunctive aripiprazole (n = 191) (starting dose 5 mg/d, dose
      adjustments 2-20 mg/d, mean end-point dose of 11.0 mg/d). The primary efficacy
      endpoint was the mean change in Montgomery-Asberg Depression Rating Scale total
      score from end of prospective treatment phase to end of randomized treatment
      phase (last observation carried forward). Mean change in Montgomery-Asberg
      Depression Rating Scale total score was significantly greater with adjunctive
      aripiprazole than placebo (-8.5 vs -5.7; P = 0.001). Remission rates were
      significantly greater with adjunctive aripiprazole than placebo (25.4% vs 15.2%;
      P = 0.016) as were response rates (32.4% vs 17.4%; P < 0.001). Adverse events
      occurring in 10% of patients or more with adjunctive placebo or aripiprazole were
      akathisia (4.2% vs 25.9%), headache (10.5% vs 9.0%), and fatigue (3.7% vs 10.1%).
      Incidence of adverse events leading to discontinuation was low (adjunctive
      placebo [1.1%] vs adjunctive aripiprazole [3.7%]). Aripiprazole is an effective
      and safe adjunctive therapy as demonstrated in this short-term study for patients
      who are nonresponsive to standard ADT.

PMID- 18344726
TI  - Efficacy of imipramine in psychotic versus nonpsychotic depression.
AB  - The purpose of the present study is to compare the efficacy of imipramine in the
      treatment of psychotic versus nonpsychotic depression. Previous studies report
      varying results of monotherapy with antidepressants in psychotic depression.
      Because psychotic depression is seriously underinvestigated, performing a post
      hoc analysis of randomized clinical trials consisting of both psychotic and
      nonpsychotic depressed patients may contribute to the discussion on the optimal
      treatment of depressed patients with mood-congruent psychotic features. A total
      of 112 patients diagnosed with major depression (Diagnostic and Statistical
      Manual of Mental Disorders, Fourth Edition) (40 with psychotic depression and 82
      without psychotic features) received treatment with imipramine for 6 weeks after
      a washout period of 7 days. Imipramine doses were adjusted to attain a predefined
      fixed plasma level. Treatment response was assessed with the Hamilton Rating
      Scale for Depression (HAM-D). A logistic regression analysis showed a
      significantly larger reduction in HAM-D score in the sample with psychotic
      features compared with the nonpsychotic sample (regression coefficient, -3.47;
      SE, 1.7; P = 0.04). According to the primary outcome criterion, that is, the
      change in HAM-D score, imipramine was significantly more effective in the sample
      with psychotic depression compared with the nonpsychotic depressed patients. The
      contradiction between our results and those of several previous studies may be
      due to the fixed plasma level dosing of imipramine refraining from concurrent
      psychotropic medication or limiting our patient sample to patients with mood
      congruent psychotic features.

PMID- 18344727
TI  - Comparison of short-term venlafaxine versus lithium monotherapy for bipolar II
      major depressive episode: a randomized open-label study.
AB  - OBJECTIVE: Practice guidelines for the initial treatment of bipolar II (BP II)
      major depressive episode (MDE) recommend mood stabilizer (MS) monotherapy or
      combined MS plus antidepressant drug (AD) therapy. We hypothesized that initial
      AD monotherapy would be superior to MS monotherapy for BP II MDE with a low
      hypomanic switch rate. METHODS: Bipolar II MDE patients were randomized to a 12
      week open-label treatment with either venlafaxine monotherapy (n = 43) or lithium
      carbonate monotherapy (n = 40). The primary outcome measure was the 28-item
      Hamilton Depression Rating Scale (HAM-D 28). The secondary outcome measures
      included the Young Mania Rating Scale (YMRS), clinical global impressions
      severity and change ratings, and the proportion of patients classified as
      responder (with > or = 50% reduction in baseline HAM-D score) or as remitter
      (final HAM-D score, < or = 8). RESULTS: Thirty-four venlafaxine-treated patients
      (79.1%) and 15 lithium-treated patients (37.5%) completed the trial (P < 0.0005).
      Venlafaxine monotherapy produced a greater reduction in HAM-D 28 scores, with a
      difference in change of -6.57 points (95% confidence interval, -11.97 to -1.18)
      (P = 0.017) between treatment conditions. There was a greater proportion of
      venlafaxine-treated (vs lithium-treated) patients classified either as treatment
      responder (58.1% vs 20.0%; P < 0.0005) or as treatment remitter (44.2% vs 7.5%; P
      < 0.0005) for the HAM-D 28 scores. There was no significant increase in mean YMRS
      scores over time in the venlafaxine (vs lithium) treatment condition, and no
      significant increase in mean YMRS scores at any study visit compared with
      baseline for either treatment. CONCLUSIONS: Results from this study suggest that
      AD monotherapy with venlafaxine may be an effective initial therapy for BP II MDE
      with a low hypomanic switch rate.

PMID- 18344728
TI  - Effects of 2-week treatment with temazepam and diphenhydramine in elderly
      insomniacs: a randomized, placebo-controlled trial.
AB  - A randomized, controlled, crossover clinical study compared 14-night treatment
      with 15 mg temazepam, 50 mg diphenhydramine, and placebo in elderly individuals
      with insomnia (mean age, 73.9 years; range, 70-89 years). Primary outcome
      measures were subjective assessments of sleep recorded on sleep diaries.
      Secondary measures were the morning-after psychomotor impairment, using the digit
      symbol substitution task and the manual tracking task, and the morning-after
      memory impairment, using a free-recall procedure. Results showed sleep
      improvements with 15 mg temazepam compared with placebo-sleep quality (mean
      score, 3.3 +/- 0.9 vs 2.9 +/- 0.8; P = 0.03), total sleep time (6.9 +/- 1.0 hours
      vs 6.3 +/-1.3 hours; P = 0.02), number of awakenings (1.5 +/- 1.3 vs 2.0 +/- 1.2;
      P < 0.001), and sleep-onset latency (25 +/- 22 minutes vs 37 +/- 25 minutes; P =
      0.03). Improvements were seen with diphenhydramine treatment compared with
      placebo on the number of awakenings only (mean, 1.7 +/- 1.1 vs 2.0 +/- 1.2; P <
      0.05). Numbers of adverse events reported were similar after all treatments,
      although there was 1 fall during temazepam treatment. Findings indicate that
      temazepam is more effective than diphenhydramine when compared with placebo at
      the doses tested, although this advantage is mitigated by the risk of falls
      associated with temazepam use. The choice of agent to use in the elderly must
      consider these relative benefits and risks.

PMID- 18344729
TI  - Venlafaxine for acute heroin detoxification: a double-blind, randomized, control
      trial.
AB  - OBJECTIVES: Dissatisfaction with current available heroin detoxification regimens
      has led to the search for alternatives. Evidences have shown that several
      neurotransmission systems, including serotonin, are involved in opioid
      withdrawal. This study investigated the efficacy and tolerability of venlafaxine,
      a serotonin-norepinephrine reuptake inhibitor, in managing heroin withdrawal
      symptoms. METHODS: This was a randomized, double-blind, and placebo-controlled 7
      day trial. Thirty-four heroin-dependent inpatients seeking detoxification were
      enrolled and assigned to either the venlafaxine (n = 15) or the placebo group (n
      = 19). The subjects received either venlafaxine 300 mg/d or placebo as their
      treatment regimen. Outcome measures were Objective Opioid Withdrawal Scale, total
      sleeping time, visual analog scale for subjective withdrawal severity, Clinical
      Global Impression scores on discharge, patient's impression of treatment, and
      amount of ancillary medications used. Data of outcome measures were analyzed by
      generalized estimating equation model. RESULTS: We analyzed the data from 20
      subjects (8 in venlafaxine group and 12 in placebo group) who remained in the
      study after the fifth day of the trial. Objective Opioid Withdrawal Scale, visual
      analog scale, and total sleeping time demonstrated a significant efficacy of
      venlafaxine compared with the placebo group (P < 0.0001, P = 0.0195, and P <
      0.0001, respectively). There was no difference in Clinical Global Impression and
      patient's impression of treatment between the 2 groups, although the placebo
      group needed more ancillary medications. CONCLUSIONS: Despite the small sample
      size, this study showed that venlafaxine is effective in alleviating withdrawal
      symptoms of heroin with good tolerability and safety.

PMID- 18344730
TI  - Escitalopram administered in the luteal phase exerts a marked and dose-dependent
      effect in premenstrual dysphoric disorder.
AB  - This is the first placebo-controlled trial evaluating the efficacy of the
      selective serotonin reuptake inhibitor (SSRI), escitalopram, in the treatment of
      premenstrual dysphoric disorder (PMDD). Women with PMDD (intention-to-treat
      population, n = 151) were treated intermittently for 3 months, during luteal
      phases only, with 10 mg/d escitalopram, 20 mg/d escitalopram, or placebo.
      Escitalopram was found to exert a marked and a dose-dependent symptom-reducing
      effect, 20 mg/d being clearly superior to 10 mg/d. Although the primary outcome
      parameter, that is, the sum of the symptoms irritability, depressed mood,
      tension, and affective lability, was decreased by 90% with 20 mg/d escitalopram,
      the effect of active treatment on breast tenderness, food craving, and lack of
      energy was more modest and not significantly different from that of placebo; this
      outcome supports our previous assumption that the former symptoms are more
      inclined to respond to intermittent administration of an SSRI than are the
      latter. Although the placebo response was high, the difference between the
      placebo group and the 20-mg/d escitalopram group with respect to the percentage
      of subjects displaying 80% or greater reduction in the rating of the cardinal
      symptom of PMDD, that is, irritability, was considerable: 30% versus 80%. Adverse
      events were those normally reported in SSRI trials, such as nausea and reduced
      libido, and were not more common in patients given 20 mg/d of escitalopram than
      in patients given the lower dose. This study supports the usefulness of
      escitalopram for the treatment of PMDD and sheds further light on how different
      components of this syndrome are differently influenced by intermittent
      administration of an SSRI.

PMID- 18344731
TI  - Antipsychotic-induced extrapyramidal side effects in bipolar disorder and
      schizophrenia: a systematic review.
AB  - OBJECTIVES: Newer atypical antipsychotics have been reported to cause a lower
      incidence of extrapyramidal side effects (EPS) than conventional agents. This
      review is to compare antipsychotic-induced EPS relative to placebo in bipolar
      disorder (BPD) and schizophrenia. METHODS: English-language literature cited in
      Medline was searched with terms antipsychotics, placebo-controlled trial, and
      bipolar disorder or schizophrenia and then with antipsychotic (generic/brand
      name), safety, akathisia, EPS, or anticholinergic use, bipolar mania/depression,
      BPD, or schizophrenia, and randomized clinical trial. Randomized, double-blind,
      placebo-controlled, monotherapy studies with comparable doses in both BPD and
      schizophrenia were included. Absolute risk increase and number needed to treat to
      harm (NNTH) for akathisia, overall EPS, and anticholinergic use relative to
      placebo were estimated. RESULTS: Eleven trials in mania, 4 in bipolar depression,
      and 8 in schizophrenia were included. Haloperidol significantly increased the
      risk for akathisia, overall EPS, and anticholinergic use in both mania and
      schizophrenia, with a larger magnitude in mania, an NNTH for akathisia of 4
      versus 7, EPS of 3 versus 5, and anticholinergic use of 2 versus 4, respectively
      Among atypical antipsychotics, only ziprasidone significantly increased the risk
      for overall EPS and anticholinergic use in both mania and schizophrenia, again
      with larger differences in mania, an NNTH for overall EPS of 11 versus 19, and
      anticholinergic use of 5 versus 9. In addition, risks were significantly
      increased for overall EPS (NNTH = 5) and anticholinergic use (NNTH = 5) in
      risperidone-treated mania, akathisia in aripiprazole-treated mania (NNTH = 9) and
      bipolar depression (NNTH = 5), and overall EPS (NNTH = 19) in quetiapine-treated
      bipolar depression. CONCLUSIONS: Bipolar patients, especially in depression, were
      more vulnerable to having acute antipsychotic-induced movement disorders than
      those with schizophrenia.

PMID- 18344732
TI  - Long-acting injectable risperidone in the treatment of subjects with recent-onset
      psychosis: a preliminary study.
AB  - Using a long-acting antipsychotic to improve adherence early in the illness may
      reduce relapse rates and promote sustained remission, thereby improving the long
      term outcome of schizophrenia. We assessed whether risperidone long-acting
      injection (RLAI) could be used safely and effectively in the treatment of recent
      onset psychosis. Fifty patients aged 15 to 43 years with newly diagnosed
      schizophreniform disorder or schizophrenia were treated with RLAI 25 to 50 mg
      every 2 weeks for 2 years. Thirty-six patients (72%) completed the trial. Of 39
      (78%) who showed a clinical response of 50%, 4 relapsed. Thirty-two patients
      (64%) achieved remission. Mean maximum increase in Extrapyramidal Symptoms Rating
      Scale total score was 1.4 (95% confidence interval, 0.61-2.10; n = 50); 10
      patients required anticholinergic medication, and 1 subject developed persistent
      dyskinesia. Prolactin levels were elevated in 18 patients, 4 of whom reported
      possible prolactin-related adverse events. Mean increase in body mass index to
      last visit for all patients was 4.8 kg/m (SD, 3.8 kg/m). The final RLAI dose was
      25 mg for 54% of patients, 37.5 mg for 30%, and 50 mg for 16%. This preliminary
      study suggests that RLAI was overall well tolerated and appears to be effective
      in recent-onset psychosis. Further investigation is warranted.

PMID- 18344733
TI  - Obsessive-compulsive symptoms in a randomized, double-blind study with olanzapine
      or risperidone in young patients with early psychosis.
AB  - BACKGROUND: The prevalence of obsessive-compulsive symptoms (OCS) in patients
      with schizophrenia is relatively high. Antipsychotics have been found to
      influence OCS. OBJECTIVE: To determine whether induction or severity of OCS
      differs during treatment with olanzapine or risperidone in young patients with
      early psychosis. METHODS: One hundred twenty-two patients with a Diagnostic and
      Statistical Manual of Mental Disorders-Fourth Edition diagnosis of schizophrenia,
      schizoaffective disorder, or schizophreniform disorder were randomized in a
      double-blind design to groups of 6 weeks' treatment with olanzapine (n = 59) or
      risperidone (n = 63), with a mean dose of 11.3 mg olanzapine and 3.0 mg
      risperidone at 6 weeks. Primary outcome measures were the mean baseline-to
      endpoint change in total score on the Yale-Brown Obsessive-Compulsive Scale (Y
      BOCS). RESULTS: Treatment with olanzapine was associated with greater decreases
      in Y-BOCS total score than treatment with risperidone in total group (N = 122: 
      2.2 vs -0.3, z = -2.651, P < 0.01), in patients with baseline Y-BOCS total score
      greater than 0 (n = 58: -5.1 vs -0.4, z = -2.717, P < 0.01), and in patients with
      baseline Y-BOCS total score greater than 10 (n = 29: -7.1 vs -0.6, z = -2.138, P
      = 0.032). CONCLUSIONS: In this randomized, 6-week, double-blind trial, we found a
      significant and clinically relevant difference in decrease in Y-BOCS scores
      favoring olanzapine compared with risperidone.

PMID- 18344734
TI  - Photo-onycholysis caused by olanzapine and aripiprazole.
AB  - Photo-onycholysis associated with drugs is an uncommon disorder. We report the
      case of a woman who developed photo-onycholysis on multiple nails after uptake of
      olanzapine. Substitution of olanzapine with aripiprazole further exacerbated the
      problem. The possible mechanisms of photo-onycholysis development by modern
      atypical antipsychotics, modulating dopamine receptors, are discussed.

PMID- 18344735
TI  - Quetiapine for the treatment of cocaine dependence: an open-label trial.
AB  - The monaminergic properties of second generation antipsychotics are prompting
      research on their use to treat cocaine dependence, with inconclusive results to
      date. In preliminary reports, the atypical antipsychotic quetiapine has shown
      promise for the treatment of substance abuse disorders. The primary objective of
      the current study was to assess the efficacy of quetiapine in reducing cocaine
      cravings and use in nonpsychotic subjects with cocaine dependence over 6 weeks of
      open-label treatment. Twenty-two cocaine-dependent, nonpsychotic men were
      initiated to open-label treatment with quetiapine (300-600 mg/d). The primary
      outcome measure was weekly self-report of cocaine cravings as assessed with the
      Brief Substance Craving Scale. Cocaine use was captured with a self-report
      Timeline Follow-back calendar, administered every 2 weeks. Side effect monitoring
      was conducted weekly, and movement disorders were assessed every 2 weeks. Intent
      to-treat regression analyses (n = 22) indicated that the Brief Substance Craving
      Scale total score decreased significantly overtime (P < 0.001). Self-reports also
      suggested decreased cocaine use. There was no treatment-related increase in
      movement disorders, and most side effects were mild. However, all subjects did
      experience sedation, and several subjects dropped out because of it. What is
      more, weight increased significantly over time (P < 0.001). Open-label quetiapine
      treatment reduced cravings and improved some aspects of cocaine dependence in
      nonpsychotic individuals. Additional research is needed to confirm the current
      findings and to further delineate the role quetiapine may play in the treatment
      of cocaine use disorders.

PMID- 18344736
TI  - Assessment of medication management ability in middle-aged and older adults with
      bipolar disorder.
AB  - Medication nonadherence is a key clinical concern in bipolar disorder (BD) across
      the life span. Cognitive deficits in older adults with BD may hinder medication
      management ability, which, in turn, may lead to nonadherence. Using an innovative
      performance-based measure of medication management ability, the Medication
      Management Ability Assessment (MMAA), we compared performance of 29 middle-aged
      older community-dwelling outpatients with BD who were clinically stable (mean
      age, 61 years; SD, 11 years; range, 45-86 years) with those of 59 normal control
      subjects (NCs) and 219 outpatients with schizophrenia. The MMAA is a role-play
      task that simulates a medication regimen likely to be encountered by older
      adults. Within the BD group, we examined the relationships of MMAA scores to
      demographic, psychiatric symptoms severity, and the Mattis Dementia Rating Scale
      (DRS) scores. The BD group made 2.8 times the errors on the MMAA than NCs (BD
      group, 6.2; SD, 5.5 vs NCs, 2.2; SD, 2.5) and did not significantly differ from
      the Schizophrenia group in errors on the MMAA. Errors in the BD group were more
      likely to be taking in too few medications as taking in too many. Within the BD
      group, a significant correlation was seen between MMAA scores and the DRS Total
      score, but not with age, education, Brief Psychiatric Rating Scale, Hamilton
      Depression Rating Scale, number of psychiatric medications, or medical
      conditions. Among DRS subscales, the Memory Subscale correlated most strongly
      with MMAA errors. This small cross-sectional study suggests that deficits in
      medication management ability may be present in later-life BD. Neurocognitive
      deficits may be important in understanding problems with unintentional
      nonadherence.

PMID- 18344737
TI  - The risk of postpartum hemorrhage with selective serotonin reuptake inhibitors
      and other antidepressants.
AB  - OBJECTIVE: Limited evidence suggests that selective serotonin reuptake inhibitor
      (SSRI) antidepressants can hinder platelet aggregation and can increase the risk
      of hemorrhage. Because antenatal depression is common and is often treated with
      antidepressants, we sought to determine if exposure to SSRI antidepressants in
      late pregnancy is associated with an increased risk of postpartum hemorrhage
      compared with non-SSRI antidepressants. METHOD: This was a population-based
      nested case-control study of women aged 16 to 45 years in Ontario, Canada, who
      received government-funded prescription coverage within 2 years before delivery.
      We identified case patients with postpartum hemorrhage and matched controls
      (1:10) without postpartum hemorrhage from the same cohort. Controls were matched
      to cases on age, mode of delivery, parity, and calendar time. We linked
      prescription claims data to hospital and physician records for the study period
      (January 1999 to March 2005). Exclusion criteria included drugs and medical
      conditions that predispose to hemorrhage, and receipt of multiple antidepressants
      in the 6 months preceding delivery. Antidepressant drug exposure was classified
      as SSRI or other agents within 90 days before delivery. RESULTS: There were 2460
      postpartum hemorrhage cases and 23,943 matched controls. The adjusted odds ratio
      for the association between postpartum hemorrhage and exposure to SSRIs within 90
      days before index date was 1.30 (95% confidence interval, 0.98-1.72) as compared
      with 1.12 (95% confidence interval, 0.62-2.01) for non-SSRIs. CONCLUSIONS:
      Selective serotonin reuptake inhibitors confer no disproportionate risk of
      postpartum hemorrhage at the time of delivery compared with non-SSRI
      antidepressants. This information may help guide decisions regarding
      pharmacotherapy for depression during pregnancy.

PMID- 18344738
TI  - Effects of PRX-00023, a novel, selective serotonin 1A receptor agonist on
      measures of anxiety and depression in generalized anxiety disorder: results of a
      double-blind, placebo-controlled trial.
AB  - PRX-00023, a serotonin 1A receptor agonist, was designed to provide high potency
      and selectivity for its target. To assess the possible therapeutic utility in
      anxiety, a randomized, double-blind, placebo-controlled trial was conducted in
      311 subjects who met the criteria of the Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition, for generalized anxiety disorder. All subjects
      underwent a 1-week placebo run-in and were randomized to receive once-daily
      capsules containing either PRX-00023 (80 mg/d) or placebo for an additional 8
      weeks. The primary outcome measure was the Hamilton Anxiety Scale (HAM-A). The
      Montgomery-Asberg Depression Rating Scale was used as a secondary endpoint to
      measure depressive symptoms. Statistical testing was performed with analysis of
      covariance, between baseline and week 8, with baseline values as a covariate. The
      anxiolytic effect of PRX-00023, compared with placebo, showed trends across all
      anxiolytic measures but failed to reach significance on the primary endpoint (HAM
      A total score). Among the components of the HAM-A total score, the anxious mood
      item was significantly different from placebo in the PRX-00023-treated group (
      1.015 vs -0.748; P = 0.02). The scores of the Montgomery-Asberg Depression Rating
      Scale were significantly improved compared with placebo at week 8 (-4.5 vs -1.6;
      P = 0.0094 in the last observation carried forward analysis). PRX-00023 was well
      tolerated; of note, there were no drug-related serious adverse events, and more
      patients discontinued due to adverse events in the placebo group (2.9%) than in
      the PRX-00023 group (1.4%). The most common adverse event was headache, observed
      in 15.7% and 10.9% of PRX-00023- and placebo-treated patients, respectively.
      Furthermore, there was no evidence of impaired sexual function, as measured by
      the Massachusetts General Hospital Sexual Function Scale. Collectively, these
      results support further clinical investigation of higher doses of PRX-00023 in
      anxiety and depression.

PMID- 18344739
TI  - High-dose ziprasidone monotherapy in bipolar I disorder patients with depressed
      or mixed episodes.

PMID- 18344740
TI  - Clinical experience with carbamazepine overdose: relationship between serum
      concentration and neurological severity.

PMID- 18344741
TI  - Aripiprazole efficacy in irritability and disruptive-aggressive symptoms: young
      mania rating scale line analysis from two, randomized, double-blind, placebo
      controlled trials.

PMID- 18344742
TI  - Acute dystonic reaction after initiating aripiprazole monotherapy in a 20-year
      old man.

PMID- 18344743
TI  - Effects of topiramate on smoking in patients with schizoaffective disorder,
      bipolar type.

PMID- 18344744
TI  - Myoclonus provoked by lamotrigine in a bipolar patient.

PMID- 18344745
TI  - Lithium overcomes the influence of 5-HTTLPR gene polymorphism on antidepressant
      response to sleep deprivation.

PMID- 18344746
TI  - Visual and coenesthetic hallucinations associated with modafinil.

PMID- 18344747
TI  - Drug-induced liver disease related to citalopram.

PMID- 18344748
TI  - Dose-related increase of intraocular pressure caused by venlafaxine use: case
      report.

PMID- 18344749
TI  - Stimulant dosing in the community treatment of adult attention
      deficit/hyperactivity disorder.

PMID- 18344750
TI  - Integrating medical and psychiatric care in patients with bipolar disorder.

PMID- 18344751
TI  - No effect of spironolactone on bulimia nervosa symptoms.

PMID- 18344752
TI  - Association of central corneal thickness and 24-hour intraocular pressure
      fluctuation.
AB  - PURPOSE: To evaluate the association between office-hour central corneal
      thickness (CCT) and 24-hour intraocular pressure (IOP) fluctuation in patients
      with glaucoma. DESIGN: Observational case-control study. METHODS: Measurements of
      IOP were obtained every 2 hours during a 24-hour period from 52 untreated
      glaucoma patients and 29 age-matched normal control subjects housed in a sleep
      laboratory. Habitual IOP measurements were obtained using a pneumatonometer in
      the sitting positions during the diurnal/wake period (7 AM to 11 PM) and in the
      supine position during the nocturnal/sleep period (11 PM to 7 AM). CCT was
      measured in all subjects using ultrasound pachymetry once during office hours.
      The association between IOP fluctuation (peak IOP-trough IOP) during the 24-hour
      period and the office-hour CCT was assessed in both glaucoma patients and healthy
      age-matched controls using Spearman rank order correlation. RESULTS: There was no
      statistically significant correlation between IOP fluctuation and CCT in
      glaucomatous (P=0.405) and normal subjects (P=0.456). CONCLUSIONS: Twenty-four
      hour IOP fluctuations were not correlated with single CCT measurements taken
      during office hours in glaucoma patients.

PMID- 18344753
TI  - Effects of central corneal thickness on the efficacy of topical ocular
      hypotensive medications.
AB  - PURPOSE: To determine the effect of central corneal thickness (CCT) on the
      efficacy of intraocular pressure (IOP)-reducing drugs in patients with ocular
      hypertension (OHT). METHODS: This retrospective study analyzed research records
      of 115 OHT patients and 97 ocular normotensive (ONT) volunteers. CCT was measured
      by slit-lamp pachymetry and IOP by pneumatonometry. The OHT patients were divided
      into Thick (>540 microm, n=52) and Thin (<or=540 microm, n=63) Cornea groups.
      Measurements in the OHT group were made after washout of all IOP-lowering drugs
      and at 1 week of treatment with latanoprost 0.005%, dorzolamide 2%, brimonidine
      0.2%, apraclonidine 0.5%, pilocarpine 2%, or unoprostone 0.15% to 1 eye and
      vehicle contralaterally. ONT volunteers also were divided into Thick (n=34) and
      Thin (n=63) Cornea groups. Results were compared between groups using unpaired t
      tests or nonparametric Wilcoxon tests and within groups using linear regression
      analyses. RESULTS: Baseline IOPs were not different between CCT groups of OHT
      patients or of ONT volunteers. After 1 week of drug treatment, IOP was
      significantly (P=0.02) lower in the OHT Thin Cornea group (16.0+/-3.0 mm Hg,
      mean+/-SD) than the OHT Thick Cornea group (17.4+/-2.8 mm Hg). There was a
      positive correlation between IOP and CCT (R=0.06, P=0.007) in OHT drug-treated
      eyes, but not OHT vehicle-treated or ONT untreated eyes. The final IOP was
      significantly lower in the Thin than the Thick Cornea group treated with
      brimonidine (P=0.02) but not with latanoprost (P=0.91). CONCLUSIONS: When dosed
      with IOP lowering drugs, eyes with thinner corneas had lower IOPs than eyes with
      thicker corneas. This suggests a reduced efficacy of some glaucoma medications in
      ocular hypertensive patients with thick corneas.

PMID- 18344754
TI  - Optic nerve head drusen and visual field loss in normotensive and hypertensive
      eyes.
AB  - OBJECTIVE: To compare visual field loss (VFL) in eyes with optic nerve head
      drusen (ONHD) with or without ocular hypertension (OHT). METHODS: The records of
      all patients aged 45 years or older with a diagnosis of ONHD at 2 centers were
      reviewed. OHT was defined as intraocular pressure >or=22 mm Hg. We categorized
      ONHD into 3 grades based on visibility on disc photographs. RESULTS: We
      identified 22 eyes (13 patients) with both ONHD and OHT and 81 normotensive eyes
      (47 patients) with ONHD. VFL was present in 20/22 (90.9%) of hypertensive eyes
      compared with 54/81 (66.7%) of normotensive eyes (P=0.03, Fisher exact test).
      Drusen grade III and OHT were both independently and significantly associated
      with greater incidence of VFL (logistic regression analysis). CONCLUSIONS: VFL
      occurs more frequently in eyes with ONHD that also have OHT. Eyes with grade III
      ONHD are at increased risk for VFL compared to eyes with grade I drusen with the
      same intraocular pressure status. Patients with OHT and ONHD should undergo close
      surveillance for disease progression and be treated appropriately to prevent
      additional VFL.

PMID- 18344755
TI  - Comparing glaucomatous optic neuropathy in primary open angle and primary angle
      closure glaucoma eyes by scanning laser polarimetry-variable corneal
      compensation.
AB  - PURPOSE: To study the retinal nerve fiber layer thickness difference between high
      tension primary open angle glaucoma (HT-POAG) and primary angle closure glaucoma
      (PACG) eyes using scanning laser polarimetry-variable corneal compensation (GDx
      VCC) in Taiwan-Chinese population; to evaluate the usefulness of the GDx VCC for
      detecting POAG and PACG eyes in Taiwan-Chinese population. PATIENTS AND METHODS:
      The study comprised 88 early to moderate glaucomatous eyes (one randomly selected
      eye from 47 HT-POAG patients and 41 PACG patients) and the control group
      consisted of 45 age-matched eyes from 45 normal individuals. Each subject
      underwent retinal nerve fiber layer thickness measurement by GDx VCC and Humphrey
      Field Analyzer visual field testing. Measured GDx VCC parameters were compared
      among groups. We also calculated the area under the receive operator
      characteristic (AROC) curve, corresponding sensitivity/specificity and best cut
      off value for each parameter in differentiating normal from POAG and PACG eyes.
      RESULTS: There was no significant difference between HT-POAG and PACG eyes in
      each parameter. The parameter with the best AROC curve for differentiating normal
      from POAG eye was nerve fiber indicator (AROC, 0.779; sensitivity=57.4%,
      specificity=100%; best cut off value >27). The parameter with the best AROC
      curves for differentiating normal from PACG eyes was temporal-superior-nasal
      inferior-temporal average (AROC, 0.829; sensitivity=46.3%, specificity=100%, best
      cut off value <51.7). CONCLUSIONS: There was no significant difference between
      the HT-POAG and PACG eyes as far as the various parameters were concerned. GDx
      VCC shows fair discriminating ability in distinguishing normal from POAG and PACG
      eyes in Taiwan Chinese population.

PMID- 18344756
TI  - A comparison of semiautomated versus manual Goldmann kinetic perimetry in
      patients with visually significant glaucoma.
AB  - PURPOSE: To determine if semiautomated kinetic perimetry (SKP) is reproducible
      and comparable to Goldmann manual kinetic perimetry (GVF). METHODS: Glaucoma
      patients were recruited to perform visual field testing using GVF and SKP.
      Specific isopters were tested, quantified, and compared. Visual field patterns
      were analyzed for shape and defect. RESULTS: Ten patients (16 eyes) underwent
      visual field studies using SKP and GVF, and 8 patients completed a second SKP on
      a different day. Individual isopter areas were similar between GVF and SKP,
      although 60% of isopters were larger on SKP by an average of 15%. This was
      statistically significant for the smaller isopters, I4e (P=0.02) and I2e
      (P=0.05). Retesting with SKP on a separate day, showed similar isopter areas (P
      values=0.3 to 1.0), however, the exact location of isopters in degrees from
      central fixation tended to vary with the smaller test object sizes. Isopter
      position in degrees from the central axis agreed in at least 3 quadrants in
      approximately 65% of fields compared. SKP visual field defects and patterns were
      similar between test strategies. CONCLUSIONS: SKP and GVF testing produce similar
      visual field results in glaucoma patients, and SKP testing seems to be reliable
      and reproducible in this population. However, overlapping isopters, typically
      associated with nonorganic vision loss, and jagged isopters were sometimes
      observed in SKP visual fields. Further study of SKP is needed to explore these
      findings.

PMID- 18344757
TI  - A comparison among Humphrey field analyzer, Microperimetry, and Heidelberg Retina
      Tomograph in the evaluation of macula in primary open angle glaucoma.
AB  - PURPOSE: It is known that macula can be affected adversely in glaucoma. In this
      study, we aimed to evaluate the functional and morphologic changes of macula in
      patients having glaucoma using Microperimeter-1 (MP-1), Humphrey field analyzer
      (HFA), and Heidelberg Retina Tomograph II (HRT-II). MATERIALS AND METHODS: This
      prospective study consisted of 43 patients having primary open angle glaucoma.
      Control group consisted of 26 normal cases. Macular threshold was evaluated with
      HFA macula threshold test and MP-1 Humphrey macula pattern. Morphometric
      evaluation of macula was performed with HRT-II. The results were evaluated by
      independent samples t test and receiver operator curves. RESULTS: Macular
      sensitivity was lower in patients having glaucoma with both HFA and MP-1 in all
      quadrants (P=0.003 for HFA and P=0.002 for MP-1). The macular thickness
      measurements obtained with HRT-II was not significant between glaucoma patients
      and control group (P=0.153). The difference between HFA and MP-1, HFA and HRT-II,
      MP-1 and HRT-II was not statistically significant (P=0.302, 0.110, and 0.481,
      respectively). CONCLUSIONS: Perimetric macular changes can occur while macular
      topographic remains stable in patients with glaucoma. MP-1 correlates with HFA in
      detecting glaucomatous visual field defect in macular area.

PMID- 18344758
TI  - Retinal nerve fiber layer thickness in normal, ocular hypertensive, and
      glaucomatous Indian eyes: an optical coherence tomography study.
AB  - PURPOSE: To determine retinal nerve fiber layer (RNFL) thickness measurements in
      normal, ocular hypertensive (OHT), and glaucomatous Asian Indian eyes. METHODS:
      This prospective observational cross-sectional study included patients with OHT,
      primary open angle glaucoma (POAG), and age-matched normal controls. The global
      and 4-quadrant average RNFL thickness was measured using the Stratus OCT. The
      main outcome measures were differences in RNFL thickness measurements between the
      3 groups. The discriminating power of each parameter was evaluated by calculating
      areas under receiver operating characteristic curves (AROCs). RESULTS: Twenty
      three eyes of 23 POAG patients, 24 eyes of 24 OHT, and 48 eyes of 48 normal
      controls were analyzed. The superior, inferior, and global RNFL measurements were
      significantly thinner in OHTs compared with normals (P=0.031, 0.019, and 0.022,
      respectively). All 5 RNFL parameters were significantly thinner in the POAG group
      compared with OHT group (P<0.001). Parameters with largest AROCs for
      distinguishing glaucoma from OHT were average and inferior average RNFL
      measurements (0.989 and 0.979, respectively). Inferior and superior RNFL
      measurements had largest AROCs (0.717 and 0.700, respectively) to distinguish OHT
      from normal eyes. CONCLUSIONS: Stratus OCT detected significant quantitative
      differences in RNFL thickness between normal, OHT, and glaucomatous Asian Indian
      eyes.

PMID- 18344759
TI  - A prospective study of early intraocular pressure changes after a single
      intravitreal triamcinolone injection.
AB  - PURPOSE: To prospectively monitor intraocular pressure (IOP) and gonioscopy
      changes within the first month after a single 4-mg intravitreal injection of
      triamcinolone acetonide (IVK) (Kenalog, Briston-Meyers Squibb, New York). DESIGN:
      Prospective comparative interventional case series. METHODS: A consecutive series
      of 28 eyes of 14 patients with no prior intravitreal injections or history of
      glaucoma were prospectively enrolled. After baseline evaluation in both eyes,
      including IOP, gonioscopy, and optic nerve evaluation, a single 4-mg IVK was
      given in a standard sterile fashion in the eye to be treated. Eyes received IVK
      for macular edema associated with retinal vein occlusions and in conjunction with
      photodynamic therapy for choroidal neovascularization secondary to age-related
      macular degeneration, ocular histoplasmosis, and high myopia. The fellow eye
      served as the control. After the injection, IOP and gonioscopy were repeated at
      1, 2, and 4-week intervals in both eyes. RESULTS: Of the 14 patients, the 5 women
      and 9 men had a mean age of 67.6 years. Mean baseline IOP of the treated and
      fellow control eyes were similar at 15.9 versus 16.6 mm Hg, respectively. The
      control eyes maintained a small IOP range (15.6 to 16.6 mm Hg) during the 1-month
      follow-up period. In the treated eyes, the mean maximum IOP was 54% above
      baseline during follow-up, compared with 11% for control eyes. Six of 14 (43%)
      treated eyes had IOP elevation to 24 mm Hg or higher with mean change of 8.6 mm
      Hg and a mean maximum IOP of 32.1 mm Hg. There was no correlation between IOP
      rise and age, sex, diagnosis, or optic nerve appearance. However, during the
      course of the study, 4 of 6 (67%) of the treated eyes that required topical drops
      for the IOP elevation had documented abnormal inferior angle changes
      characterized by pigmented particulate matter in the inferior angle not present
      at the baseline exam. The most frequent time point for an IOP elevation that
      required treatment was at 2-week postinjection. No eyes required surgical
      management of IOP during the course of this 4-week study. CONCLUSIONS: We
      observed a significant IOP rise in eyes after a single intravitreal injection of
      4 mg of triamcinolone within 1 month of injection. In this study, the most
      frequent time point that required IOP treatment was at 2-week postinjection,
      suggesting that early and frequent monitoring of IOP should be considered. Two
      thirds of eyes that required medical control of IOP developed gonioscopy changes,
      characterized by particulate matter in the inferior angle, not present at
      baseline. Eyes that developed gonioscopic changes were 5 times more likely to be
      treated for IOP elevation than those without gonioscopic findings.

PMID- 18344760
TI  - Decreased cardiovagal regulation in exfoliation syndrome.
AB  - PURPOSE: To investigate the parasympathetic cardiovascular regulation, baroreflex
      sensitivity (BRS), and pulse wave velocity (PWV) in exfoliation syndrome (XFS).
      METHODS: Heart rate variability indices [standard deviation of all RR intervals
      (SDNN); the mean of absolute successive differences (RMSSD); the percentage of
      intervals differing by >50 ms from the preceding interval (pNN50); low frequency
      power, and high frequency power], as well as BRS and PWV, were determined on 27
      consecutive white XFS patients and 20 white control subjects under standard
      circumstances, with controlled breath rate of 0.25 Hz. The paired t test, the
      Mann-Whitney U test, and the Fisher exact test were used for comparisons.
      RESULTS: There was no significant difference between the XFS and control groups
      in sex distribution, age, heart rate, blood pressure, body mass index, systemic
      diseases, or medication. But in XFS patients, SDNN (mean+/-SD, 24+/-7.3 vs. 49+/
      16.5 ms), RMSSD (17+/-7.3 vs. 45+/-29.1 ms), pNN50 (1.6%+/-2.5% vs. 17.7%+/
      25.9%), high frequency (112+/-109 vs. 479+/-554 ms), and BRS (4.64+/-2.12 vs.
      9.49+/-4.76 ms/mm Hg for BRS+ and 5.28+/-2.16 vs. 10.29+/-4.62 ms/mm Hg for BRS-)
      were all significantly lower than in the control group (P<0.01 for each
      parameter). Low frequency was also reduced in XFS (72+/-55 vs. 253+/-241 ms)
      (P=0.027). In XFS, PWV was significantly increased compared with the control
      group (11.6+/-4.1 vs. 9.3+/-2.2 m/s) (P=0.023). DISCUSSION: Our results suggest a
      clinically and statistically significant impairment of cardiovagal regulation and
      impairment of conduit artery function in XFS patients.

PMID- 18344761
TI  - Nonpenetrating glaucoma surgery: meta-analysis of recent results.
AB  - PURPOSE: To evaluate the efficacy of nonpenetrating glaucoma surgery for open
      angle glaucoma with respect to target intraocular pressure (IOP) and severity of
      glaucoma. MATERIALS AND METHODS: A literature search with the terms
      "nonpenetrating glaucoma surgery, deep sclerectomy (DS), viscocanalostomy (VC),
      and open angle glaucoma" was carried out for the reports in the last 5 years.
      Studies encompassing only combined glaucoma and cataract surgery were excluded.
      Measurement of effectiveness was determined on the basis of achievement of target
      IOP. Data related to postoperative goniopuncture and needling with antimetabolite
      application were noted. RESULTS: The percentage of cases achieving <or=21 mm Hg
      was 48.6% after primary DS, 68.7% after DS with implant, 67.1% after DS with
      antimetabolite, 51.1% after primary VC, and 36.8% after VC with antimetabolite or
      implant. Visual field parameters were almost exclusively not available; whereas
      cup/disk ratio and target IOP lower than 21 mm Hg were available in very few
      reports. With lower set IOP targets, the rates of success varied between 35% and
      86% for DS, and between 10% and 67% for VC. The mean follow-up of the studies
      were mostly in the range of 3 years. CONCLUSIONS: Nonpenetrating glaucoma surgery
      seems to provide IOP reduction into the high teens. Its potential to achieve
      lower target IOPs seems to be low. Longer-term studies, with data related to
      glaucoma severity and proper target IOPs are required.

PMID- 18344762
TI  - Barriers to glaucoma drug delivery.
AB  - Topical medications remain the mainstay of glaucoma treatment. This review will
      aim to cover the pharmacokinetics of topically applied drops, the ocular barriers
      to drug delivery, and the role of ophthalmic drug formulation in enhancing drug
      delivery to the target tissue while minimizing side effects and increasing
      patient compliance. Recent advances in surgical techniques, therapeutic
      approaches, and material sciences have produced exciting new therapies for ocular
      diseases. The development of new vehicles and drug formulations that require less
      patient compliance is also discussed, as are the routes of drug delivery for
      neuroprotection.

PMID- 18344763
TI  - Potential contamination of the G-probe used for transscleral cyclodiode.
AB  - AIM: To present a case where we noted occult contamination of the G-probe used
      for transscleral cyclodiode and to critically analyze the techniques used for
      making a G-probe suitable for repeated use. MATERIALS AND METHODS: Close
      microscopic examination of the G-probes used once for transscleral cyclodiode was
      done and a critical review of the literature on practice of reuse of the G-probe
      and the techniques used to "cleanse" the probe before reuse was performed.
      RESULTS: We noticed microscopic contamination of the G-probe by the tear film
      fluid in all the probes examined by us. The review of literature indicates that
      repeated use of the G-probe is not uncommon. The types of techniques used for
      making it suitable for repeated use indicate that it is not universally
      recognized that the lumen of the G-probe can accumulate fluid during the
      procedure, which makes it potentially hazardous when used for other patients.
      CONCLUSIONS: In our opinion the G-probe should not be reused as inadequately
      reprocessed G-probe can lead to risk of nosocomial infections, serious iatrogenic
      complications, and medico-legal problems.

PMID- 18344764
TI  - Quality nursing care on the line.

PMID- 18344765
TI  - New center to champion nursing in America established to avert nurse shortage.

PMID- 18344766
TI  - Standard 40: local anesthesia.

PMID- 18344767
TI  - Infusion reactions triggered by monoclonal antibodies treating solid tumors.
AB  - Monoclonal antibodies (mAb) are potent agents with significant therapeutic
      advantages and represent the new standard of care in oncology. Although fairly
      well tolerated, a major health issue with mAbs is the development of infusion
      reactions that can range in severity from mild to life threatening. Therefore, it
      is critical to know how to manage these reactions when the first symptoms appear.
      Oncology nurses need to be proactive in monitoring, assessing, and managing
      infusion reactions throughout the entire course of therapy. Nurses are also
      instrumental in developing a protocol on how to address infusion reactions.
      Building a partnership with patients and caregivers ensures that patients are
      safely treated and can fully benefit from mAb therapy.

PMID- 18344768
TI  - Catheter outcomes in home infusion.
AB  - Intravenous catheter outcomes are a prominent topic for healthcare providers
      whose patients receive intravenous medications. There are thousands of products
      being marketed today claiming to improve catheter outcomes, thus improving
      overall patient outcomes and reducing provider costs associated with catheter
      infections and replacement. Catheter-related bloodstream infections (CR-BSIs)
      cost hospitals between $5000 and $34,000 per infection, and 12% to 25% of
      bloodstream infections are attributable to patient mortality. Products that claim
      to prevent CR-BSIs and subsequently reduce the number of bloodstream infections
      are a multimillion-dollar industry.

PMID- 18344769
TI  - The expanding role of the infusion nurse in radiographic interpretation for
      peripherally inserted central catheter tip placement.
AB  - The role of the registered nurse has evolved over time from a limited caregiver
      providing care to the patient under the absolute authority of a physician to an
      involved participant of the healthcare team. This has resulted in added
      responsibility and the incorporation of a higher skill level. In institutions
      across the country, nurses are involved in improving the quality of patient care
      and assisting in the provision of care in a timely manner with decreased delays
      in treatment and improved identification of complications associated with
      procedures. In this article, the process for investigating the potential for
      expanding the role of the registered nurse to include determination of
      peripherally inserted central catheter tip placement is discussed.

PMID- 18344770
TI  - Pediatric trauma resuscitation: initial fluid management.
AB  - Fluid management is a vital component in the resuscitative care of the injured
      child. The goal of fluid resuscitation is to restore tissue perfusion without
      compromising the body's natural compensatory mechanism. Recent literature has
      questioned the timing, type, and amount of fluid administration during the
      resuscitative phase. When managing a pediatric resuscitation, it is imperative to
      use a variety of age-appropriate physiologic parameters because reliance on blood
      pressure alone will lead to delayed recognition of shock. Establishing vascular
      access, via peripheral intravenous, central venous, or intraosseous catheter,
      should be a high nursing priority. Hemorrhage control and fluid resuscitation of
      an injured child remains a top priority of trauma care. Early intravenous access
      with appropriate fluid administration continues to be a universal treatment for
      the hypotensive trauma patient. Fluid resuscitation in the early phase of care,
      whether in the field, emergency department, or operating room, should be targeted
      toward perfusing critical organs, such as the brain and heart. Once obvious
      bleeding is controlled, the overall goal for fluid management centers on
      maintaining oxygen delivery to perfuse vital structures with enough oxygen and
      energy substrates to maintain cellular function, thus avoiding tissue ischemia.
      However, specific issues around timing and type of fluid administration, once
      thought to be straightforward, have triggered increasing investigation of current
      beliefs.

PMID- 18344773
TI  - Limiting nurse overtime, and promoting other good working conditions, influences
      patient safety.

PMID- 18344774
TI  - The Professional Excellence Council: implications for all Forces of Magnetism.

PMID- 18344775
TI  - Pediatric nurse staffing and quality of care in the hospital setting.
AB  - Indicators of quality and nurse staffing in pediatrics are distinct from adults.
      A retrospective, correlational, linear mixed model design was used to describe
      relationships between pediatric nurse staffing and 5 indicators of quality care
      from a convenience sample of 7 academic children's hospitals. Key findings
      supported a strong inverse relationship between the proportion of hours of
      pediatric nursing care delivered by registered nurses and the rate of occurrence
      of central line (P < .001) and bloodstream infections (P < .05). Supplemental
      nurse staffing hours also demonstrated relationships between bloodstream
      infections and parent/family complaints.

PMID- 18344776
TI  - Creating a culture of improvement: experience of a pediatric cystic fibrosis
      center.
AB  - Quality improvement (QI) efforts at the University of Alabama at
      Birmingham/Children's Hospital Cystic Fibrosis Center began in the spring of
      2004, with a collaborative sponsored by the Cystic Fibrosis Foundation. As the
      authors gained experience with QI processes, significant system changes ensued.
      In this article, we describe how the center created a culture of improvement that
      has resulted in significant improvements in clinical outcomes in our patient
      population.

PMID- 18344778
TI  - Nurses as practice change facilitators for healthy behaviors.
AB  - This study used nurses as practice change consultants to help primary care
      medical practices improve their delivery of health behavior services to patients.
      Nurse consultants worked with 20 practices from 2 healthcare systems. In each
      practice, the nurses helped clinicians and staff to develop a practice-specific
      protocol so that they could identify and intervene with the health behavior of
      their patients. As a result of the nurse consultant intervention, health behavior
      delivery was improved. This article describes the specific methods and the
      lessons learned through this study. We encourage practices to use nurse
      consultants as one way of improving quality of care.

PMID- 18344779
TI  - Using principles of diffusion of innovation to improve nursing home care.
AB  - Principles of diffusion of innovation were used to change care provided to people
      with dementia in 9 nursing homes. Use of these principles was associated with
      increased assessment in response to behavior change, increased administration of
      analgesics, and a significant decrease in resident behavioral symptoms. Results
      of this study support the emerging consensus that diffusion of innovation is an
      effective model for making changes in performance of healthcare organizations.

PMID- 18344780
TI  - What nurses want: diffusion of an innovation.
AB  - We investigated the usability of personal digital assistants (PDAs) to improve
      research utilization and timely access to electronic practice information to
      assist in clinical decisions. Nurses used a decision support tool on a PDA to
      collect point-of-care outcomes data. Follow-up interviews documented usability.
      Nurses liked the portability and size of the PDA, as well as ease of use of the
      PDA software. Electronic decision support tools at point of care have the
      potential to improve nurses' research utilization and quality of care.

PMID- 18344781
TI  - Treatment practices of diabetic ketoacidosis at a large teaching hospital.
AB  - A retrospective chart review of 55 medical records of adults treated for diabetic
      ketoacidosis (DKA) identified areas of treatment that delayed the improvement of
      DKA. There was a positive correlation between time to initiation of insulin
      infusion and resolution of anion gap. Sixty-six percent of cases did not have the
      recommended overlap between intravenous and subcutaneous insulin. Opportunity
      exists to educate nurses as experts to partner with their physician colleagues to
      manage DKA.

PMID- 18344782
TI  - Association between rehabilitation care practices and care quality in long-term
      care facilities.
AB  - This article analyzes the association between rehabilitation care practices and
      quality outcomes in Finland and represents unit-level (n = 256) associations
      between rehabilitation nursing and quality outcomes. Units classified as units
      providing a high frequency of rehabilitation care practices had better outcomes
      in 2 of 5 quality outcomes.

PMID- 18344783
TI  - Testing the reliability and validity of self-efficacy and outcome expectations of
      restorative care performed by nursing assistants.
AB  - The primary aims of this study were to determine the reliability and validity of
      2 measures: the Nursing Assistant Self-efficacy for Restorative Care Scale and
      the Nursing Assistant Outcome Expectations for Restorative Care Scale. This study
      included 386 nursing assistants from 8 nursing homes. The findings provide some
      support for the reliability and validity of these measures on the basis of Rasch
      analysis, confirmatory factor analysis, and convergent validity.

PMID- 18344784
TI  - Increasing nurses' knowledge and behavior changes in nonpharmacological pain
      management for children in China.
AB  - This study implemented pain education for Chinese nurses using a pre-post test
      design and compared their use of nonpharmacological methods in children's
      postoperative pain management. Results show that nurses' use of most of these
      methods for pain relief increased significantly, which helped to improve the
      quality of care for children. This study enriches nurses' knowledge in children's
      pain management and develops evidence for practice by demonstrating the need for
      hospitals to provide continuous pain education to nurses.

PMID- 18344785
TI  - A crisis: fear toward a possible H5N1 pandemic.
AB  - This survey investigated individuals' fear when faced with a possible H5N1 human
      to-human pandemic. It was conducted in Taiwan toward the end of 2005 with 452
      participants, including physicians, nurses, and university students. The results
      showed that for physicians and nurses, the perceived possibility of an avian flu
      outbreak and the belief that hospitals lacked sufficient infection control
      measures contributed to their personal fear of an avian flu epidemic. For
      students, the perceived possibility of avian flu being a threat to humans
      contributed to their personal fear. With sufficient, up-to-date information,
      unnecessary fear, and/or panic can be avoided.

PMID- 18344786
TI  - Historical underpinnings. 2008 marks the 40th anniversary of the Wound, Ostomy
      and Continence Nurses (WOCN) Society.

PMID- 18344787
TI  - Context for WOC practice: the economics of our practice, demonstrating our value
      and identifying gaps in patient care services.

PMID- 18344788
TI  - Writing for publication: avoiding common ethical pitfalls.

PMID- 18344789
TI  - Katrina survivor.

PMID- 18344790
TI  - Intestinal diversion (colostomy or ileostomy) in patients with severe bowel
      dysfunction following spinal cord injury.
AB  - BACKGROUND: Spinal cord injury (SCI) affects motor and sensory nervous integrity
      resulting in paralysis of lower or both upper and lower extremities, as well as
      autonomic nervous system function resulting in neurogenic bowel. SCI leads to
      diminished or lost sensations of the need to defecate or inability to distinguish
      the presence of gas versus liquid versus solid stool in the rectal vault. Sensory
      loss, incomplete evacuation of stool from the rectal vault, immobility, and
      reduced anal sphincter tone increase the risk of fecal incontinence.
      Gastrointestinal symptoms are associated with depression, anxiety, and
      significant impairments in quality of life (QOL) in a significant portion of
      persons with SCI. OBJECTIVES: 1. To compare clinical, functional, or quality of
      life outcomes in spinal cord injured patients with gastrointestinal symptoms
      managed by conservative measures versus intestinal diversion (colostomy or
      ileostomy). 2. To identify complications associated with ostomy surgery in
      patients with bowel dysfunction and SCI. SEARCH STRATEGY: A systematic review of
      electronic databases MEDLINE and CINAHL (from January 1960 to November 2007) was
      undertaken using the following key words: (1) ostomy, (2) stoma, (3) colostomy,
      and (4) ileostomy. Boolean features of these databases were used to combine these
      terms with the key word "spinal cord injuries." Prospective and retrospective
      studies that directly compared clinical, functional, QOL outcomes or satisfaction
      among patients with intestinal diversions to patients managed by conservative
      means were included. RESULTS: Creation of an ostomy in selected patients provides
      equivocal or superior QOL outcomes when compared to conservative bowel management
      strategies. Both colostomy and ileostomy surgery significantly reduce the amount
      of time required for bowel management. Patients who undergo ostomy surgery tend
      to be satisfied with their surgery, and a significant portion report a desire to
      be counseled about this option earlier. There are no clear advantages when
      functional, clinical, or QOL outcomes associated with colostomy are compared to
      those seen in SCI patients undergoing ileostomy. IMPLICATIONS FOR PRACTICE: 1.
      The WOC nurse plays a pivotal role in both conservative bowel management and the
      decision to undergo ostomy surgery. 2. Preoperative stoma site marking is vital
      for the best surgical outcome. 3. The system best suited to an individual is
      based on a variety of factors including but not limited to stoma location, type
      of effluent, peristomal plane and contours, and the individual's capabilities and
      preferences. 4. Some individuals with a sigmoid or descending colostomy may
      benefit from colostomy irrigation as a management method. 5. Postoperatively,
      assessment of pressure points for signs of tissue breakdown, evaluation of
      treatment methods for existing pressure ulcers with suitable modification, and
      support surface assessment should be included in ongoing annual follow-up visits.

PMID- 18344791
TI  - An innovative enterostomal therapy nurse model of community wound care delivery:
      a retrospective cost-effectiveness analysis.
AB  - PURPOSE: A Canadian specialty nursing association identified the necessity to
      examine the role and impact of enterostomal (ET) nursing in Canada. We completed
      a retrospective analysis of the cost-effectiveness and benefits of ET nurse
      driven resources for the treatment of acute and chronic wounds in the community.
      DESIGN: This was a multicenter retrospective pragmatic chart audit of 3 models of
      nursing care utilizing 4 community nursing agencies and 1 specialty company owned
      and operated by ET nurses. An analysis was completed using quantitative methods
      to evaluate healing outcomes, nursing costs, and cost-effectiveness. MAIN OUTCOME
      MEASURES: Kaplan-Meier estimates were calculated to determine the average time to
      100% healing of acute and chronic wounds and total nursing visit costs for
      treatment in a community setting. Average direct nursing costs related to
      management of each wound were determined by number of nursing visits and related
      reimbursement for each visit. A Monte Carlo simulation method was used to help
      account for costs and benefits in determination of cost-effectiveness between
      caring groups and the uncertainty from variation between patients and wounds.
      RESULTS: Three hundred sixty chronic wounds and 54 acute surgical wound charts
      were audited. Involvement of a registered nurse (RN) with ET or advanced wound
      ostomy skills (AWOS) in community-level chronic and acute wound care was
      associated with lower overall costs mainly due to reduced time to 100% closure of
      the wound and reduced number of nursing visits. The differences in health
      benefits and total costs of nursing care between the ET/AWOS and a hybrid group
      that includes interventions developed by an ET nurse and followed by general
      visiting nurses that could include both RNs and registered practical nurses is an
      expected reduction in healing times of 45 days and an expected cost difference of
      $5927.00 per chronic wound treated. When outcomes were broken into ET/AWOS
      involvement categories for treatment of chronic wounds, there was a significantly
      faster time to 100% closure at a lower mean cost as the ET/AWOS involvement
      increased in the case. For acute wound treatment, the differences in health
      benefits and total costs between the ET/AWOS and a hybrid nursing care model were
      an expected reduction in healing times of 95 days and an expected cost difference
      of $9578.00 per acute wound treated. Again, there was a significant difference in
      healing times and reduced mean cost as the ET/AWOS became more involved in the
      treatment. The financial benefit to the Ontario Ministry of Health and Long-Term
      Care is estimated to increase as the involvement of nurses with ET/AWOS specialty
      training increases. CONCLUSIONS: The greater the involvement both directly and
      indirectly of an ET/AWOS nurse in the management of wounds, the greater the
      savings and the shorter the healing times.

PMID- 18344793
TI  - Make sense of wound care billing: turn your cents into reimbursement dollars.
AB  - How does a clinician determine appropriate billing for wound care services? For
      Medicare and Medicaid patients, billing-related regulations are developed and
      promulgated by the US Centers for Medicare & Medicaid Services (CMS). This
      article will show how to access and use the CMS Web site as a resource for
      finding necessary information pertaining to billing guidelines and appropriate
      codes, including edits that prevent billing multiple procedures together and the
      use of modifiers that may allow an additional billing. Further discussion focuses
      on the importance of regular visits to this Web site since it is regularly
      updated as changes occur in billing or reimbursement policies. Therefore,
      investing the time to check the site for the latest updates can make a critical
      difference in your success with reimbursement for wound care services.

PMID- 18344795
TI  - The effect of Web-based Braden Scale training on the reliability and precision of
      Braden Scale pressure ulcer risk assessments.
AB  - OBJECTIVE: To evaluate the effect of Web-based Braden Scale training on the
      reliability and precision of pressure ulcer risk assessments made by registered
      nurses (RN) working in acute care settings. DESIGN: Pretest-posttest, 2-group,
      quasi-experimental design. SETTING AND SUBJECTS: Five hundred Braden Scale risk
      assessments were made on 102 acute care patients deemed to be at various levels
      of risk for pressure ulceration. Assessments were made by RNs working in acute
      care hospitals at 3 different medical centers where the Braden Scale was in
      regular daily use (2 medical centers) or new to the setting (1 medical center).
      INSTRUMENT: The Braden Scale for Predicting Pressure Sore Risk was used to guide
      pressure ulcer risk assessments. A Web-based version of the Detroit Medical
      Center Braden Scale Computerized Training Module was used to teach nurses correct
      use of the Braden Scale and selection of risk-based pressure ulcer prevention
      interventions. RESULTS: In the aggregate, RN generated reliable Braden Scale
      pressure ulcer risk assessments 65% of the time after training. The effect of Web
      based Braden Scale training on reliability and precision of assessments varied
      according to familiarity with the scale. With training, new users of the scale
      made reliable assessments 84% of the time and significantly improved precision of
      their assessments. The reliability and precision of Braden Scale risk assessments
      made by its regular users was unaffected by training. CONCLUSION: Technology
      assisted Braden Scale training improved both reliability and precision of risk
      assessments made by new users of the scale, but had virtually no effect on the
      reliability or precision of risk assessments made by regular users of the
      instrument. Further research is needed to determine best approaches for improving
      reliability and precision of Braden Scale assessments made by its regular users.

PMID- 18344798
TI  - Continence care for older people in England and Wales: data from a national
      audit.
AB  - INTRODUCTION: A number of policy documents have identified deficiencies in
      continence services in England and Wales, and have called for the development of
      integrated services. A national audit was conducted to assess the quality of
      continence care for older people and whether these requirements have been met.
      METHODS: The audit studied incontinent individuals aged 65 years and older. Each
      site returned data on organizational structure and the process of 20 patient's
      care. Data were submitted via the Internet, all were anonymous. RESULTS: The
      national audit was conducted across England, Wales, and Northern Ireland. Data on
      the care of patients/residents with bladder problems were returned by 141 of 326
      (43%) Primary Care Trusts, 159 of 196 (81%) secondary/acute care trusts (198
      hospitals), and 29 of 309 (9%) invited care homes. Fifty-eight percent of Primary
      Care Trusts, 48% of hospitals, and 74% of care homes reported that integrated
      continence services existed in their area. While basic provision of care appeared
      to be in place, the audit identified deficiencies in the organization of services
      and in the assessment and management of urinary incontinence in the elderly.
      CONCLUSION: The requirement for integrated continence services has not yet been
      met. Assessment and care by professionals directly looking after the older person
      were often lacking. There is an urgent need to reestablish the fundamentals of
      continence care into the practice of medical and nursing staff, and action needs
      to be taken with regard to the establishment of truly integrated quality services
      in this neglected area of practice.

PMID- 18344799
TI  - Use of an absorbent dressing specifically for fecal incontinence.
AB  - PURPOSE: Use of an absorbent product is a self-care strategy for managing fecal
      incontinence that protects against visible soiling. The purpose of this study was
      to examine use of a small surgical dressing that can be placed between the
      buttocks to absorb leaked feces. DESIGN: Cross-sectional survey. SUBJECTS AND
      SETTING: A survey was mailed to 75 randomly selected community-living people in
      25 states and the District of Columbia, who ordered the dressing more than once
      within the past year. Thirty-six people (age = 55 +/- 16 years mean +/- SD), 57%
      men and 94% white responded. INSTRUMENT: A 48-question survey that included
      questions asked about demographics and general health, emotional states (eg,
      anxiety and depression), bowel pattern and incontinence, quality of life, and use
      of an anorectal dressing was developed for this study. The survey also contained
      2 tools, the Fecal Incontinence Severity Index and the Fecal Incontinence Quality
      of Life instrument. The Fecal Incontinence Severity Index is a tool that enables
      valid assessment of fecal incontinence severity using patient recall of symptoms
      of frequency and type of bowel leakage. The Fecal Incontinence Quality of Life
      instrument results in a valid and reliable evaluation of fecal incontinence
      specific quality of life using 4 domains of lifestyle, coping/behavior,
      depression/self-perception, and embarrassment. RESULTS: The fecal incontinence
      severity score was 28 +/- 14 (mean +/- SD); 79% leaked loose/liquid feces, 50%
      leaked daily, and leaked feces remained between the buttocks in 64%; 21% also
      leaked urine. Eighty-five percent experienced incontinence-associated dermatitis.
      Of those who used the dressing, 50% were men. The anorectal dressing was
      preferred to a pad by 92%, prevented soiling in 88%, and its ability to stay in
      place was rated very good or good by 76%. Eighty percent of respondents rated the
      dressing's comfort very good or good; 85% rated its overall effectiveness very
      good or good. Use of the dressing lessened anxiety about fecal soiling in 81% and
      was thought to improve quality of life in 76%. CONCLUSION: An anorectal dressing
      offers an effective, comfortable alternative to a pad for absorbing leaked feces
      that seems acceptable to men.

PMID- 18344800
TI  - Ostomy care.

PMID- 18344801
TI  - Antegrade irrigations of a surgically reconstructed Hartmann's pouch to treat
      intractable diversion colitis.

PMID- 18344803
TI  - The importance of early treatment with doxycycline in human ehrlichiosis.
AB  - Human ehrlichiosis is a serious disease that can be fatal if not treated
      appropriately. We examined patients with a clinical presentation consistent with
      the syndrome of ehrlichiosis and a positive blood polymerase chain reaction (PCR)
      test for all known Ehrlichia species or Anaplasma phagocytophilum admitted to
      Barnes-Jewish Hospital in St. Louis, MO, from 1996 to 2006. Patients who had
      doxycycline initiated within the first 24 hours of admission to the hospital were
      compared with patients who did not have empiric doxycycline therapy. A total of
      46 patients had a positive blood PCR test for Ehrlichia or Anaplasma
      phagocytophilum, and 28 (60.9%) had a delay in doxycycline therapy. At
      presentation, patients with a delay in therapy were more likely to present with
      an abnormal lung exam and altered mental status. None of the patients
      experiencing a delay in doxycycline treatment had the diagnosis of ehrlichiosis
      documented at the time of hospital admission, compared with 13 (72.2%) of the
      patients who were treated empirically (p < 0.001). Patients not started on
      doxycycline at hospital admission had a significantly increased rate of transfer
      to the intensive care unit (39.3% vs. 0%; p < 0.001) and requirement for
      mechanical ventilation (28.6% vs. 0%; p < 0.001). Patients with a treatment delay
      also had a longer hospital stay (12.3 +/- 11 d vs. 3.9 +/- 1.9 d, respectively; p
      < 0.001) and a longer length of illness (20.9 +/- 14.2 d vs. 8.9 +/- 2.7 d,
      respectively; p = 0.001). These data suggest that clinicians living in an area
      where Ehrlichia is endemic should have a high suspicion for ehrlichiosis, and a
      low threshold for instituting empiric antibiotic therapy with doxycycline.

PMID- 18344804
TI  - Vasculitis involving the breast: a clinical and histopathologic analysis of 34
      patients.
AB  - Vasculitis of the breast (VB) may be an isolated finding or a manifestation of
      systemic vasculitis. In the current study we sought to characterize isolated VB
      (IVB) and compare it to VB in the setting of systemic vasculitis. We studied VB
      cases in the literature and patients cared for at our institution. We analyzed
      clinical, laboratory, and histologic features (including vessel size and type of
      inflammatory infiltrates); course of illness; biopsy procedure; and treatment.
      Based on the presence of localized or systemic disease at the time of disease
      presentation and during the follow-up, we divided patients into 3 groups: IVB
      (Group 1), VB with proven or indirect evidence of systemic vasculitis (Group 2),
      and VB with possible systemic involvement (Group 3). We identified a total of 34
      cases of VB (30 from PubMed [National Library of Medicine, Bethesda, MD] and 4
      from our pathology database). All patients presented with breast lesions, which
      were the only expression of disease in 16 (47%). Eighteen, 6, and 10 patients
      belonged to Group 1, 2, and 3, respectively. Constitutional symptoms were present
      less often in Group 1. Musculoskeletal symptoms occurred only in Groups 2 and 3.
      Patients in Groups 2 and 3 had higher erythrocyte sedimentation rates and lower
      hemoglobin levels, and also received corticosteroids more frequently than those
      in Group 1. No differences were found in the other analyzed parameters between
      groups. In summary, VB is uncommon, and in about half of the cases, occurs in the
      form of IVB. Histologic characteristics do not correlate with disease extent. In
      IVB patients, constitutional and musculoskeletal manifestations are usually
      absent. Such patients generally do not require systemic therapy and may be cured
      by resection alone.

PMID- 18344806
TI  - Heat shock protein A1B 1267 polymorphism is highly associated with risk and
      prognosis of hepatocellular carcinoma: a case-control study.
AB  - We conducted a case-control study to elucidate the role of heat shock protein A1B
      (HSPA1B) 1267 single nucleotide polymorphism (SNP) on the risk and prognosis of
      hepatocellular carcinoma (HCC). Subjects enrolled included 150 pairs of sex- and
      age-matched HCC patients and unrelated controls. Genomic DNA was typed for
      HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length
      polymorphism. The frequencies of the HSPA1B P2/P2 genotype and the HSPA1B P2
      allele in HCC patients were higher than in unrelated controls (each p = 0.0001).
      Multivariate analysis identified the following independent risk factors for HCC:
      HSPA1B P1/P2 genotype (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.07
      5.11), HSPA1B P2/P2 genotype (OR, 12.06; 95% CI, 4.43-32.79), hepatitis B surface
      antigen (HBsAg) (OR, 25.95; 95% CI, 11.88-56.68), and antibodies to hepatitis C
      virus (anti-HCV) (OR, 70.43; 95% CI, 21.89-226.64). There was an additive
      interaction between HSPA1B P2 allele carriers and the presence of either HBsAg
      (synergy index = 2.48) or anti-HCV (synergy index = 1.52). However, as HSPA1B1267
      SNP is a silent mutation, it is a surrogate genetic marker for increasing risk of
      HCC. Our findings indicate that patients with chronic hepatitis B/hepatitis C
      virus infection who harbor this SNP represent a high-risk group for HCC. They
      should receive more intensive surveillance for early detection of HCC. Moreover,
      patients with the HSPA1B P2 allele had significantly longer survival (p =
      0.002).The limitations of this study include the unknown functional significance
      of the HSPA1B1267 polymorphism, the relatively small sample size, the fact that
      this was not a prospective study of cases and controls, and the questionable
      generalizability of the findings given the specific ethnic composition of the
      population studied.

PMID- 18344805
TI  - Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a
      gradient of severity.
AB  - We describe the clinical features of 28 patients with juvenile dermatomyositis
      (JDM) and 1 patient with adult-onset dermatomyositis (DM), all of whom developed
      lipodystrophy (LD) that could be categorized into 1 of 3 phenotypes, generalized,
      partial, or focal, based on the pattern of fat loss distribution. LD onset was
      often delayed, beginning a median of 4.6 years after diagnosis of DM. Calcinosis,
      muscle atrophy, joint contractures, and facial rash were DM disease features
      found to be associated with LD. Panniculitis was associated with focal
      lipoatrophy while the anti-p155 autoantibody, a newly described myositis
      associated autoantibody, was more associated with generalized LD. Specific LD
      features such as acanthosis nigricans, hirsutism, fat redistribution, and
      steatosis/nonalcoholic steatohepatitis were frequent in patients with LD, in a
      gradient of frequency and severity among the 3 sub-phenotypes. Metabolic studies
      frequently revealed insulin resistance and hypertriglyceridemia in patients with
      generalized and partial LD. Regional fat loss from the thighs, with relative
      sparing of fat loss from the medial thighs, was more frequent in generalized than
      in partial LD and absent from DM patients without LD. Cytokine polymorphisms, the
      C3 nephritic factor, insulin receptor antibodies, and lamin mutations did not
      appear to play a pathogenic role in the development of LD in our patients. LD is
      an under-recognized sequela of JDM, and certain DM patients with a severe,
      prolonged clinical course and a high frequency of calcinosis appear to be at
      greater risk for the development of this complication. High-risk JDM patients
      should be screened for metabolic abnormalities, which are common in generalized
      and partial LD and result in much of the LD-associated morbidity. Further study
      is warranted to investigate the pathogenesis of acquired LD in patients with DM.

PMID- 18344807
TI  - The clinical spectrum of IgM-related amyloidosis: a French nationwide
      retrospective study of 72 patients.
AB  - Immunoglobulin M (IgM)-related amyloidosis remains a rare and little-known
      complication of monoclonal IgM-associated disorders. We sought to determine the
      clinical and laboratory presentation, response to treatment, and outcome of
      patients with IgM-related amyloidosis in the era of new therapeutic approaches.
      We conducted a retrospective study in 29 French centers to identify patients with
      monoclonal IgM and biopsy-proven amyloidosis; we reviewed patients' records and
      collected relevant clinical and laboratory data. We identified 72 patients with
      IgM-related amyloidosis. Systemic primary amyloidosis (AL) was present in 64,
      peritumoral AL in 5, and systemic secondary amyloidosis (AA) in 3 patients. A
      peculiar pattern of relatively frequent lymph node (31%) and lung (17%)
      involvement was noted in patients with systemic AL amyloidosis. Response to
      alkylating agents was poor, with a hematologic response in 37%, a complete
      remission in 0%, and an organ response in 21%. Response to hematopoietic stem
      cell transplantation showed a hematologic response in 100% with complete
      remission in 75% and an organ response in 75%. Purine analogs and rituximab
      induced a hematologic response in 73% and 60%, respectively, with complete
      remission in 9% and 0% and an organ response in 55% and 0%, respectively. In
      multivariate analysis, prognostic factors for survival were serum albumin level <
      or =3.5 g/dL (p = 0.018) and heart involvement (p = 0.0034). Further prospective
      studies are needed in patients with IgM-related amyloidosis, with special
      emphasis on treatment options: hematopoietic stem cell transplantation and purine
      analogs could represent the most effective therapies. The identification of
      adverse prognostic factors of survival could be useful for those managing and
      making treatment decisions for these patients.

PMID- 18344808
TI  - Bird fancier's lung: a series of 86 patients.
AB  - Bird fancier's lung (BFL) is one of the most common types of hypersensitivity
      pneumonitis. Nevertheless, the criteria for diagnosing this condition are not
      standardized. The current study is an in-depth investigation into the clinical
      characteristics of BFL in the largest series examined for this purpose by a
      single group, to our knowledge, taking into account the acute, subacute, or
      chronic clinical presentation. From 1977 to 2003, BFL was diagnosed in 86
      patients using a homogeneous protocol. Data from the clinical history and
      physical examination were analyzed, as well as the results from the following
      complementary examinations: laboratory analyses, specific serum IgG antibodies
      determination, chest X-ray, chest computed tomography (CT), pulmonary function
      testing, immediate hypersensitivity skin testing, delayed cutaneous
      hypersensitivity testing, bronchofibroscopy with bronchoalveolar lavage (BAL)
      and/or transbronchial biopsy, bronchial challenge testing, and surgical lung
      biopsy. In addition, clinical and epidemiologic characteristics were determined
      in a control group of 60 pigeon breeders who did not meet the diagnostic criteria
      of BFL. Eighty-six patients (21 men and 65 women) with a mean age of 47 years
      were studied. Seven (8%) patients were younger than 15 years of age at the time
      of the diagnosis. In 3 cases, the disease was caused by exposure to feather
      filled bedding. Nearly 1 in 5 patients was diagnosed in the chronic phase of the
      disease. The mean diagnostic delay was 1.6 years overall, and 3.2 years in
      patients diagnosed in the chronic phase of the disease. Among the 17% of patients
      with chronic disease, the mean interval from initiation of exposure to diagnosis
      was 16 years, a higher value than in the acute or subacute presentation forms.
      Dyspnea and cough were the most common clinical symptoms (98% and 82%,
      respectively), and nearly 25% had grade III or IV dyspnea at diagnosis. Only 18%
      of patients experienced chest tightness, a symptom classically considered to be
      frequent in this condition. Erythrocyte sedimentation rate was elevated (>30
      mm/h) in 44% of patients. Urinary calcium was elevated in 20% of patients.
      Angiotensin-converting enzyme was not elevated in any of the patients in which it
      was measured. Lactate dehydrogenase increases were found in 51% of patients.
      Specific IgG antibodies to avian antigens were documented in 92% of BFL patients,
      but also in 87% of pigeon breeder controls. The most frequent radiologic finding
      was an interstitial pattern in 79% of patients. Common chest CT features were
      ground glass areas (68%) and a mosaic pattern (61%); areas of emphysema were
      found in 7/41 (17%) patients, 5 of whom had never smoked. Two patients had a CT
      pattern of pulmonary fibrosis indistinguishable from idiopathic pulmonary
      fibrosis. Immediate hypersensitivity skin testing with bird sera and pigeon bloom
      was positive in 78% and 100% of BFL patients, respectively, and in 64% and 88% of
      control pigeon breeders, respectively. Almost one-third of the patients (29%)
      presented an anergic response on delayed cutaneous hypersensitivity testing.
      Restrictive ventilatory impairment was the most frequent functional pattern
      (77%), although 9% and 4% showed a pure obstructive and mixed pattern,
      respectively. The carbon monoxide diffusing capacity was decreased (<80% of the
      predicted value) in 85% of cases. Forty-one percent of patients had PaO2 <60 mm
      Hg at diagnosis when blood gas analysis was performed. Lymphocytosis (>20%
      lymphocytes) was documented in 83% of patients who underwent BAL, with a similar
      frequency in the 3 presentation forms: 70% acute, 89% subacute, and 85% chronic.
      In addition, inversion of the CD4/CD8 ratio (<1) was observed in 62% of the
      patients, but 38% of cases showed a CD4 predominance. The characteristic triad of
      histopathologic findings in hypersensitivity pneumonitis was found in only 9% of
      patients undergoing transbronchial biopsy, but at least 1 of these findings was
      seen in 69%. Surgical lung biopsy was undertaken in 14/86 (16%) patients; the
      complete triad was observed in 50% and at least 1 finding in 100%. In 54/86 (63%)
      patients, the diagnosis was confirmed by bronchial challenge testing, a test with
      a sensitivity of 92% and specificity of 100%. BFL is a potentially severe disease
      that can progress to respiratory failure secondary to pulmonary fibrosis or
      chronic obstructive pulmonary disease, as a form of chronic occupational
      respiratory disease. Respiratory symptoms in exposed patients, including children
      and adults who have only 1 pet bird at home, should raise the suspicion of BFL.
      Diagnosis in the chronic phase is frequent, and the delay to diagnosis was
      greatest in these cases. Elevated urinary calcium, lactate dehydrogenase, and
      erythrocyte sedimentation rate in a bird fancier may constitute a combined marker
      for suspected BFL. Chest CT frequently discloses emphysema and a pattern of
      idiopathic pulmonary fibrosis in some patients. An anergic response on delayed
      cutaneous hypersensitivity testing is not infrequent. The presentation with
      respiratory failure and the predominance of CD4 T lymphocytes in some patients'
      BAL are both remarkable. Lymphocytosis on BAL also persists in the chronic phase
      of the disease. Bronchial challenge testing has a high diagnostic yield, and
      surgical lung biopsy is not needed to reach the final diagnosis in the vast
      majority of cases.

PMID- 18344812
TI  - Standards of care and professionalism: why it matters.
AB  - The discipline of nursing is constantly changing in harmony with our patient
      needs and desires. Expanding healthcare knowledge, increased nursing knowledge,
      and new and evolving healthcare sites, structures, and technologies all have
      contributed to the need and desire for specialty organizations to provide clear
      statements of their scopes of practice and standards of care. This will ensure
      continued understanding and acknowledgment of nursing's varied professional
      contributions in today's healthcare environment.

PMID- 18344814
TI  - Core curriculum for plastic surgical nursing: psychosocial care of the plastic
      surgical patient.

PMID- 18344816
TI  - Breast reconstruction using tissue expanders: assessing patients' needs utilizing
      a holistic approach.
AB  - Breast cancer is the most common diagnosed cancer in women. One out of 8 women is
      diagnosed with this disease (). Today many women are candidates for breast
      reconstruction and opt for reconstructive surgery at the time of mastectomy.
      Plastic surgical nurses provide a vital link in assessing and assisting patients
      to acquire and assimilate the necessary information required to make informed
      decisions regarding reconstruction. Although there are a variety of options in
      breast reconstruction, the purpose of this article is to discuss tissue expansion
      after mastectomy for breast restoration. The article identifies the needs women
      may have both preoperatively and postoperatively. Orem's self-care theory model
      is used to describe roles nurses may assume to assist patients in decision making
      and performance of self-care activities during the reconstructive process.

PMID- 18344818
TI  - Nursing care of posttraumatic stress disorder after anesthesia awareness.
AB  - Anesthesia awareness can cause adverse psychological symptoms in patients after
      surgery. Although rare, posttraumatic stress disorder (PTSD) has been documented
      in surgical patients who have a history of previous trauma or maladaptive coping
      patterns. Plastic surgical nurses should assess all patients for anesthesia
      awareness postoperatively, recognize the diagnostic criteria of PTSD, and offer
      support of psychiatric referrals if indicated.

PMID- 18344819
TI  - Have you heard? The saga of wrong site surgery continues.

PMID- 18344820
TI  - Laundering scrubs.

PMID- 18344821
TI  - Ten tips for patients.

PMID- 18344823
TI  - Sculptra use in HIV-associated lipodystrophy.

PMID- 18344824
TI  - New CMS ruling and what it means.

PMID- 18344825
TI  - How case managers impact patient lives and healthcare dollars.

PMID- 18344826
TI  - Discharge planning for the uninsured: an opportunity for case managers.

PMID- 18344827
TI  - Case manager role definitions: do they make an organizational impact?
AB  - PURPOSE OF STUDY: This study examined 2 case management delivery models related
      to defined case manager role responsibilities in a large midwest hospital. Of
      interest was whether organization-wide outcomes related to reduction in length of
      stay (LOS) could be achieved by altering the case manager's role functions across
      medical, surgical, and cardiology units in general, intermediate, and intensive
      levels of care. In addition, there was curiosity about the timing of the
      admission and whether LOS would be influenced by the experience of the case
      manager with new role functions. The first model encompassed a traditional case
      management model where the case manager's primary functions were discharge
      planning and utilization review. The second model, the full immersion model,
      decreased the case manager's caseloads and expanded role functions to encompass
      daily expectations for chart review, electronic documentation, and communication
      with members of the interdisciplinary team. PRIMARY PRACTICE SETTING: Acute care
      hospital inpatient medical, surgical, and cardiology care units. METHODS AND
      SAMPLE: A causal-comparative retrospective study that included 39,017 medical,
      surgical, and cardiology inpatients who received care on general, intermediate,
      and intensive care units. Descriptive and inferential statistics were used to
      analyzed LOS in the traditional and full immersion models across clinical
      specialty units and levels of care. IMPLICATION FOR CASE MANAGEMENT PRACTICE:
      Statistically significant reductions in LOS were achieved using the full
      immersion model of case management across clinical specialties and levels of
      care. In addition, the timing of the admission during the implementation of the
      full immersion model was not statistically significant, highlighting that
      organizational impacts could be expected at the time of implementation of the
      model and that the experience of the case manager with the roles functions did
      not have a negative impact on achieving reduction in LOS with the full immersion
      model.

PMID- 18344829
TI  - Reducing unnecessary Medicare hospital admissions for chest pain in Arizona and
      Florida.
AB  - PURPOSE/OBJECTIVES: Each year in the United States, more than 4.4 million
      patients with chest pain (DRG 143) present to emergency departments. Many of
      these admissions do not have documented justification to support an acute
      inpatient admission. Two Medicare quality improvement organizations identified
      this as a common theme, and special projects were designed and implemented to
      reduce the incidence of inappropriate hospital admissions for chest pain in their
      states (Florida and Arizona). One commonality to both intervention projects was
      use of the case management protocol (CMP). PRIMARY PRACTICE SETTING(S): Acute
      care hospitals. FINDINGS/CONCLUSIONS: As a result of the special projects, in
      Florida, there was a 67% reduction in projected admission denials and a 48%
      overall reduction in chest pain discharges among participating hospitals. In
      Arizona, the rate of inappropriate 1-day admissions for DRG 143 was reduced 42%
      from baseline to remeasurement for the participating hospitals; the absolute
      number of DRG 143 one-day admissions was reduced by 90%. Of the 10 Arizona
      hospitals that used the case management protocol, 8 met or exceeded the project
      goals. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: 1. Although outpatient
      observation admission status has been around for many years, there remain
      confusion and resistance to its use. The definitions of clinical status, level of
      care, and patient status are not well defined, and choosing the correct pathway
      for each patient can be complex. This article helps clarify "Observation vs.
      Inpatient"admission status and details lessons learned in reducing resistance. 2.
      Use of the case management protocol requires a hospital to define case management
      roles and responsibilities. This is a critical but often neglected task. 3. Use
      of case management for determining correct patient status is growing. With new
      Centers for Medicare & Medicaid Services initiatives, including the recovery
      audit contractors, case management is a viable solution to maintaining the fiscal
      health of hospitals.

PMID- 18344831
TI  - Is your client's back pain "rapidly reversible"? Improving low back care at its
      foundation.
AB  - PURPOSE/OBJECTIVES: To convey a valuable and greatly misunderstood paradigm for
      evaluating and treating low back pain (LBP) and its extensive scientific
      evidence. PRIMARY PRACTICE SETTING(S): Low back pain is a highly prevalent and
      very expensive health dilemma. But by using a paradigm called Mechanical
      Diagnosis and Therapy (a.k.a. McKenzie methods), it is now possible to identify a
      very large LBP subgroup whose pain is rapidly reversible, meaning that it can
      often be eliminated quickly, with return to full function using a single, patient
      specific direction of simple, yet precise, end-range low back exercises and some
      posture modifications. This interesting subgroup includes patients with both
      acute and chronic LBP as well as both LBP-only and sciatica with neural deficits.
      FINDINGS/CONCLUSIONS: This special form of clinical assessment can detect which
      patients are in this large, rapidly reversible subgroup and which ones are not.
      Of the numerous studies targeting Mechanical Diagnosis and Therapy (MDT), three
      have focused on patients whose persisting pain had led to recommendations of disc
      surgery where 50% were then found to still have a rapidly reversible disc problem
      with high rates of nonsurgical rapid recovery. If patients are never assessed in
      this way, this reversibility remains undiscovered and these patients commonly
      undergo potentially unnecessary surgery. IMPLICATIONS FOR CASE MANAGEMENT
      PRACTICE: Armed with knowledge of this subgroup, how to identify it, the
      considerable supportive scientific evidence and strongly beneficial implications
      of utilizing this MDT paradigm, case managers are positioned to have an immensely
      positive impact on the care of LBP. Tremendous cost savings and greatly improved
      clinical outcomes are available by utilizing this form of evidence-based MDT
      care.

PMID- 18344832
TI  - A leadership focus on evidence-based practice: tools for successful
      implementation.
AB  - PURPOSE/OBJECTIVES: Case managers grapple with best methods to infuse case
      management evidence into their practice. This article examines the role of each
      case manager as a leader in evidence-based practice (EBP) and emphasizes proven
      strategies for case management leaders to move EBP into their case management
      environment. Special focus is placed on steps to establish a practice culture
      supportive of EBP, creating the organizational infrastructure to support EBP, and
      practical tips for success. PRIMARY PRACTICE SETTING: This article applies to any
      case management practice setting. FINDINGS/CONCLUSIONS: Employing a systematic
      model to move the evidence into the case management practice setting results in
      improved patient, case manager, and organizational outcomes. IMPLICATIONS FOR
      CASE MANAGEMENT PRACTICE: Case management service provision based on the
      established evidence base creates a more legally and ethically sound practice. A
      change in practice to EBP will increase individual case managers' leadership
      abilities, thus establishing a stronger and more satisfied employee base.
      Utilization of a well-planned approach to incorporate evidence into practice
      results in higher levels of success and improves patient and organizational
      outcomes.

PMID- 18344834
TI  - Case managers as miracle workers.

PMID- 18344835
TI  - Practicing effectively amid ineffectiveness and other lessons of accountability
      for the new health and human services professional.

PMID- 18344836
TI  - Physical injuries in worker's compensation: why use behavioral medicine?

PMID- 18344838
TI  - Important lessons learned.

PMID- 18344839
TI  - Ethical dilemma.

PMID- 18344840
TI  - Managing the occupational injury case: do you manage or monitor?

PMID- 18344841
TI  - What's new in Shock, April 2008?

PMID- 18344842
TI  - Pulmonary levels of high-mobility group box 1 during mechanical ventilation and
      ventilator-associated pneumonia.
AB  - High-mobility group box (HMGB) 1 is a recently discovered proinflammatory
      mediator that contributes to acute lung injury. We determined HMGB-1 levels in
      bronchoalveolar lavage fluid of patients during mechanical ventilation (MV) and
      ventilator-associated pneumonia (VAP). Bronchoalveolar lavage fluid was obtained
      from patients who were ventilated for 5 h because of an elective surgical
      procedure ("short-term MV"; n = 40) or for several days because of respiratory
      failure without acute lung injury ("long-term MV"; n = 10) and from patients who
      developed unilateral VAP (n = 4). Ten healthy volunteers served as controls. In
      healthy volunteers, HMGB-1 levels were low (median, 1.6 ngmL(-1); interquartile
      range [IQR], 0.7-3.7 ng mL(-1)). Although HMGB-1 levels were elevated after short
      term MV, differences were not statistically significant compared with healthy
      volunteers (1.7 ng mL(-1); IQR, 0.8-8.5 ng mL(-1), P = 0.493 vs. healthy
      volunteers; P = 0.250 vs. start of MV). However, HMGB-1 levels were significantly
      higher in "long-term" MV patients (11.7 ng mL(-1); IQR, 8.7-37.0 ng mL(-1); P <
      0.0001 vs. healthy volunteers). With unilateral VAP, HMGB-1 levels from the
      infected lung.were 17.4 (IQR, 8.5-23.2) ng mL(-1) (P = 0.014 vs. healthy
      controls); these levels were not different from those measured in the
      contralateral noninfected lung (P = 0.625). Summarized, long-term MV is
      associated with increased HMGB-1 levels in contrast to "short-term" MV. In
      addition, HMGB-1 levels during VAP are increased compared with healthy
      volunteers; however, they are not different from those found in patients
      intubated and mechanically ventilated for a similar period of time.

PMID- 18344844
TI  - Reliability of Tuffier's line as an anatomic landmark.
AB  - STUDY DESIGN: The level of Tuffier's line was assessed on 200 standing and 60
      prone lumbar radiographs. Sex, height, weight, and body mass index (BMI) were
      correlated with the radiograph findings. OBJECTIVE: To determine whether the
      level of Tuffier's line is associated with sex, height, weight, or BMI. SUMMARY
      OF BACKGROUND DATA: Tuffier's line (intercristal line) is a commonly used
      landmark for identification of the L4-L5 interspace; however, multiple studies
      have identified that this landmark is unreliable. METHODS: The level of Tuffier's
      line was assessed retrospectively on 200 standing anteroposterior lumbar
      radiographs and correlated with sex. Prospectively, the level of Tuffier's line
      was assessed on 60 prone posteroanterior lumbar radiographs and correlated with
      sex, height, weight, and BMI. RESULTS: In men, the intercristal line most often
      intersected the L4 body or inferior endplate. In women, the intercristal line
      most often intersected the L5 body or superior endplate. Weight and BMI had no
      correlation with Tuffier's line. Subjects with a Tuffier's line through L4 were
      taller than those with a Tuffier's line through L5. CONCLUSION: Tuffier's line
      demonstrated predictable sex-related differences: men had an intercristal line
      that most often intersected the L4 body or inferior endplate whereas the women's
      intercristal line most often intersected the L5 body or superior endplate.
      However, because the actual level of Tuffier's line may vary from the L4 body to
      the L5 body, the intercristal line is insufficient to use as the sole landmark
      for assessing spinal segmental level.

PMID- 18344845
TI  - Comparison of animal discs used in disc research to human lumbar disc: axial
      compression mechanics and glycosaminoglycan content.
AB  - STUDY DESIGN: Experimental measurement and normalization of in vitro disc axial
      compression mechanics and glycosaminoglycan and water content for several animal
      species used in intervertebral disc research. OBJECTIVE: To compare normalized
      axial mechanical properties and glycosaminoglycan and water content from other
      species to those of the human disc to aid in selection and interpretation of
      results in animal disc studies. SUMMARY OF BACKGROUND DATA: There is a lack of
      mechanical and biochemical comparative data from animal intervertebral discs with
      respect to the human disc. METHODS: Intervertebral disc axial mechanical
      properties, glycosaminoglycan, and water content were evaluated for 9 disc types
      in 7 mammalian species: the calf, pig, baboon, sheep, rabbit, rat and mouse
      lumbar, and the cow and rat tail. Disc area and height were used for calculation
      of the normalized mechanical parameters. Glycosaminoglycan content was normalized
      by dry weight. RESULTS: Many directly measured mechanical parameters varied by
      orders of magnitude. However, these parameters became comparable and often did
      not show significant differences after geometric normalization. Both
      glycosaminoglycan and water content revealed similarity across species.
      CONCLUSION: Disc axial mechanics are very similar across animal species when
      normalizing by the geometric parameters of disc height and area. This suggests
      that the disc tissue material properties are largely conserved across animal
      species. These results provide a reference to compare disc axial mechanics and
      glycosaminoglycan and water composition of experimental animal models to the
      human lumbar disc, to aid in both selection and interpretation of experimental
      disc research.

PMID- 18344846
TI  - The incidence of intravascular penetration in medial branch blocks: cervical,
      thoracic, and lumbar spines.
AB  - STUDY DESIGN: Clinical observational study. OBJECTIVE: To quantify the incidence
      of inadvertent intravascular injections in spinal medial branch blocks in a
      clinical setting. SUMMARY OF BACKGROUND DATA: Previous research established the
      rate of inadvertent intravascular injection in lumbar medial branch blocks at 8%.
      The incidence of intravascular injection in cervical and thoracic medial branch
      blocks has not been reported previously. This study establishes the rate of
      inadvertent intravascular injection in patients receiving medial branch blocks of
      the cervical and thoracic spines. Further, this study reports a significantly
      lower rate of inadvertent intravascular injection for lumbar medial branch blocks
      than previously reported. METHODS: Patients were originally referred to the
      clinic, for diagnosis and treatment of chronic spinal origin somatic pain. Medial
      branch blocks were then performed as diagnostic procedures to confirm the
      zygapophysial joint(s) as the suspected source of pain. Blocks were performed by
      experienced practitioners on nonidentified patients over a 3-year period.
      Clinical observations were recorded for 14,312 separate medial branch block
      levels. The level of the spine and the incidence of inadvertent intravascular
      injections were recorded. RESULTS: This study demonstrates that the overall
      incidence of intravascular penetration in medial branch blocks is rare, with an
      overall rate of 3.5%. This study also establishes the rate of intravascular
      injection for levels within the spine: the cervical spine is likely to be
      intravascular 3.9% of the time and the lumbar spine 3.7%, whereas the thoracic
      spine is significantly lower, with just 0.7% injections reported as
      intravascular. Significant differences were also observed between individual
      vertebral levels. CONCLUSION: The false-negative rate for medial branch blocks is
      likely to be lower than previously reported. The rate of inadvertent
      intravascular injection for thoracic medial branch blocks is 0.7%. Cervical and
      lumbar medial branch blocks are associated with an overall rate of 3.9% and 3.7%,
      respectively. Although these rates are lower than previously reported, the
      incidence of false-negative blocks still justifies the use of contrast to confirm
      nonvascular injection.

PMID- 18344847
TI  - The effects of the degenerative changes in the functional spinal unit on the
      kinematics of the cervical spine.
AB  - STUDY DESIGN: The sagittal kinematics of the cervical spine was evaluated using
      kinematic magnetic resonance imaging (kMRI). OBJECTIVE: To investigate the effect
      of degenerative changes in the functional spinal unit on cervical kinematics by
      using kMRI. SUMMARY OF BACKGROUND DATA: Few studies have, thus far, by using MR
      images, described the contribution of degenerative changes in the functional
      spinal unit to cervical kinematics; however, the exact cervical kinematics
      remains uncertain. METHODS: A total of 289 consecutive symptomatic patients
      underwent dynamic cervical MRI in flexion, neutral, and extension postures. All
      digital measurements and calculations of the variations in segmental angular
      motion were automatically performed by an MR analyzer using true MR images with
      77 predetermined points marked on each image. Each segment was assessed based on
      the extent of intervertebral disc degeneration (Grades 1-3) and cervical cord
      compression (groups A-C) observed on T2-weighted MR images. RESULTS: The
      segmental mobility of the segments with severe cord compression and moderate disc
      degeneration tended to be lower than that of the segments with severe cord
      compression and severe disc degeneration, and a significant difference was
      observed in the segmental mobility of the C5-C6 segment. Moreover, in all
      segments with moderate disc degeneration, the segmental mobility was
      significantly reduced in the presence of severe cord compression, as compared
      with no compression. However, in segments with severe disc degeneration, no
      significant differences were observed between the segmental mobility of the cord
      compression groups. CONCLUSION: Our results suggest that cervical cord
      compression may cause deterioration of cervical cord function and kinematic
      changes in the cervical spine. We hypothesize that the spinal cord may
      potentially protect its functions from dynamic mechanical cord compression by
      restricting segmental motion, and these mechanisms may be closely related to the
      intervertebral discs.

PMID- 18344848
TI  - Atypical cervical spondylotic myelopathy mimicking intramedullary tumor.
AB  - STUDY DESIGN: Case report and a review of the literature. OBJECTIVE: We report
      the case of a young man with a short course of progressive cervical myelopathy
      (CM). Cervical magnetic resonance imaging (MRI) revealed a stenosis of the
      cervical spinal canal at C4-C6 and an atypically enlarged intramedullary high
      intensity extending from C1-T1 (T2-weighted) with contrast enhancement at C4-C5
      (T1-weighted). Neurologic and radiologic diagnosis therefore favored a tumor of
      the spinal cord. SUMMARY OF BACKGROUND DATA: CM is a clinical diagnosis of mostly
      degenerative origin in older patients that features circumscribed high-intensity
      signals near the point of compression in T2-weighted MRI. Contrast enhancement in
      those high-intense areas is rarely described in the literature, and the
      differentiation from neoplastic and infective lesions might be very difficult in
      these cases. METHODS: Retrospective case study with follow-up examination and MRI
      control 3 months after surgery. RESULTS: The patient was decompressed and
      stabilized from dorsally, and a biopsy was taken. The exact diagnosis of a
      myelopathy and an exclusion of a neoplastic origin succeeded through
      histopathological examination. Three months after first surgery, the patient had
      improved significantly and underwent an additional anterior stabilization, while
      the MRI remained almost unchanged. CONCLUSION: In case of a fast progressive CM
      with atypical radiographic appearance initial decompression with inspection of
      the spinal cord and a short-term clinical follow-up with an MRI control might be
      the procedure of choice, if a clear diagnosis for a causative treatment cannot be
      made. In still suspicious cases, a biopsy could be considered to exclude a
      neoplastic or inflammatory process.

PMID- 18344849
TI  - If one vertebroplasty is good, two must be better.

PMID- 18344850
TI  - The effect of muscle relaxant on the paraspinal muscle blood flow: a randomized
      controlled trial in patients with chronic low back pain.
AB  - STUDY DESIGN: A randomized controlled trial. OBJECTIVE: To investigate the effect
      of muscle relaxant for muscle blood flow at the trunk muscle in patients with
      chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: Paraspinal muscle
      function is widely believed to play a role and considered to be of etiologic
      significance in LBP, and intramuscular pressure increases and blood flow
      decreases in the flexion position. Decrease in oxygenated hemoglobin at the trunk
      muscle is seen in patients with LBP. METHODS: A total of 74 male patients with
      LBP lasting more than 6 months were randomized to 3 treatment groups: (1)
      physical therapy only (control) (n = 25), (2) administration of eperisone
      hydrochloride (EMPP) for 4 weeks (n = 24), and (3) McKenzie therapy (n = 25). The
      primary outcome variables, observed at 2 and 4 weeks, are the Japanese Orthopedic
      Association LBP score, visual analogue scale (VAS), Faces Pain Scale-Revised, and
      SF-36. Intramuscular oxygenation was evaluated using near-infrared spectroscopy
      during lumbar extension and flexion, and oxygenated hemoglobin and deoxygenated
      hemoglobin were compared. RESULTS: VAS was significantly lower at 4 weeks in the
      McKenzie group than in the control group. There were no significant changes at 2
      weeks in all parameters, however, the relative change of oxygenated hemoglobin
      during lumbar extension at 4 weeks was significantly higher in the EMPP group
      when compared with the other 2 groups. The relative change of deoxygenated
      hemoglobin during lumbar flexion showed a significant difference at 4 weeks in
      the EMPP group when compared with the control group. CONCLUSION: Administration
      of EMPP for 4 weeks improved the LBP in VAS, though not as effective as McKenzie
      therapy. Our data demonstrated the effects of eperisone hydrochloride on
      paraspinal muscle hemodynamics improving intramuscular oxygenation during lumbar
      extension and flexion in patients with chronic LBP.

PMID- 18344851
TI  - The effect of relative needle diameter in puncture and sham injection animal
      models of degeneration.
AB  - STUDY DESIGN: Biomechanical study and literature review. OBJECTIVES: To quantify
      the acute effect of needle diameter on the in vitro mechanical properties of
      cadaver lumbar discs in the rat and sheep. To review published in vivo animal
      studies and evaluate disc changes with respect to the relative needle size.
      SUMMARY OF BACKGROUND DATA: There are many cases where a disc needle puncture or
      injection is applied to animal models: puncture injuries to induce degeneration,
      chemonucleolysis to induce degeneration, and delivery of disc therapies. It is
      not clear what role the size of the needle may have in the outcome. METHODS:
      Mechanics were measured after sham phosphate buffered saline injection with a 27
      G or 33 G needle in the rat and with a 27 G needle in the sheep. A literature
      review was performed to evaluate studies in which animal discs were treated with
      a needle puncture or a sham injection. For each study, the ratio of the needle
      diameter to disc height (needle:height) was calculated. RESULTS: When the rat was
      injected with a 27 G needle (52% of disc height), the compression, tension, and
      neutral zone stiffnesses were 20% to 60% below preinjected values and the neutral
      zone length was 130% higher; when injected with a 33 G needle (26% of disc
      height), the only affected property was the neutral zone length, which was only
      20% greater. When the sheep was injected with a 27 G needle (10% of disc height),
      none of the axial properties were different from intact, the torsion stiffness
      was not different, and the torque range was 15% smaller. Twenty-three in vivo
      studies in the rat, rabbit, dog, or sheep were reviewed. The disc changes
      depended on the ratio of needle diameter to disc height as follows: significant
      changes were not observed for needle:height less than 40%, although between 25%
      and 40% results were variable and some minor nonsignificant effects were
      observed, disc changes were universal for needle:height over 40%. CONCLUSION: A
      needle puncture may directly alter mechanical properties via nucleus pulposus
      depressurization and/or anulus fibrosus damage, depending on the relative needle
      size. As more basic science research is aimed at treating disc degeneration via
      injection of therapeutic factors, these findings provide guidance in design of
      animal studies. Such studies should consider the relative needle size and include
      sham control groups to account for the potential effects of the needle injection.

PMID- 18344852
TI  - Wear of an experimental metal-on-metal artificial disc for the lumbar spine.
AB  - STUDY DESIGN: In vitro wear simulation. OBJECTIVE: To determine the type and
      amount of wear produced by experimental metal-on-metal artificial discs for the
      lumbar spine. To minimize the amount of wear by changing the carbon content,
      clearance, and presence of a keel and notch. SUMMARY OF BACKGROUND DATA: In
      contrast to the extensive number of hip joint replacement simulator studies
      examining the effects of individual design variables on wear, existing artificial
      lumbar disc wear publications have measured wear using only the final version of
      each product. That is, the effects of individual variables such as material,
      diameter, or clearance on wear of artificial discs are not known, even though the
      importance of such variables has been established in artificial hip wear studies.
      METHODS: Experimental metal-on-metal artificial discs for the lumbar spine were
      tested in a 3-station, biaxial spine wear simulator designed and constructed by
      the investigators. Two versions of the implants were manufactured with
      differences in carbon content, clearance, and the presence of a keel.
      Additionally, implants were tested with or without a surgical notch. RESULTS: The
      wear rates of the experimental metal-on-metal lumbar discs in the current study
      ranged from 6.2 to 15.8 mm3/million cycles. However, changing the carbon content
      of the ball from low to high, decreasing the initial clearance, and eliminating
      the anteroposterior keel reduced the wear rate from 12.4 to 7.6 mm3/million
      cycles. Furthermore, removing the surgical notch reduced the wear rate from 7.6
      to 6.2 mm3/million cycles. The surface damage was generally consistent with low
      lubrication and varying degrees of abrasive and fatigue wear, with impingement of
      nonbearing surfaces observed at 1.5 million cycles for the longer-term test.
      CONCLUSION: Although the implants tested in the current study were experimental,
      the results suggest that metal-on-metal lumbar discs have the potential to
      produce wear of this magnitude and mechanism in vivo. Therefore, careful
      consideration of individual design variables, including those considered in the
      current study, is necessary to avoid production of excessive wear in artificial
      lumbar discs.

PMID- 18344853
TI  - Biomechanics of the anterior longitudinal ligament during 8 g whiplash simulation
      following single- and contiguous two-level fusion: a finite element study.
AB  - STUDY DESIGN: A computational study of anterior longitudinal ligament (ALL)
      strain in the cervical spine following single- and 2-level fusion during
      simulated whiplash. OBJECTIVE: To evaluate how cervical fusion alters the peak
      strain of the ALL in the adjacent motion segments. SUMMARY OF BACKGROUND DATA:
      Although an in vitro study of ALL strain during whiplash has been conducted in
      healthy cervical spines, no such study has been performed in a cervical spine
      with fused segments. It has been demonstrated that the loss of motion following
      fusion results in increased strain in the adjacent motion segments. However, the
      biomechanics of the adjacent motion segments during high energy acceleration
      deceleration simulations have not been widely reported. Accordingly, we
      investigated the peak strain of the ALL following single- and 2-level fusion
      during simulated whiplash. METHODS: A detailed finite element (FE) model of the
      human body in the driver-occupant position was used to investigate cervical
      hyperextension injury. The cervical spine was subjected to simulated whiplash at
      8 g acceleration and peak ALL strains were computed. The results were validated
      against published experimental data. This validated FE model was then modified to
      simulate single- and 2-level fusion and tested under identical loading
      conditions. RESULTS: The mean increase in peak ALL strain at the motion segment
      immediately adjacent to the level of fusion was 15.5% for single-level fusion
      when compared with 40.8% in 2-level contiguous fusion (P = 0.019). CONCLUSION:
      Cervical arthrodesis increases peak ALL strain in the adjacent motion segments.
      Two-level fusion increased ALL strain in the adjacent motion segments, on
      average, greater than single-level fusion did. Disc arthroplasty and other
      techniques that provide stability without loss of flexibility may be beneficial
      in patients undergoing multiple-level fusion. Detailed FE models such as ours can
      provide strong correlation with experimentally determined data.

PMID- 18344854
TI  - Influence of location, fluid flow direction, and tissue maturity on the
      macroscopic permeability of vertebral end plates.
AB  - STUDY DESIGN: We implemented a pilot study in a growing animal model. The
      macroscopic permeability of the vertebral endplates was measured. The influence
      of location, tissue maturity, and fluid flow direction was quantified. OBJECTIVE:
      We hypothesized that the macroscopic permeability of vertebral endplate may
      decrease with maturity of the vertebral segment. SUMMARY OF BACKGROUND DATA: The
      alternation of loading induced by the diurnal cycle generates convective flux
      into the vertebral segment with the dominant flow path through the vertebral
      endplates. The alteration of mass transport at the disc-vertebrae interface may
      interrupt the mechanobiologic balance, and have an effect such as degenerative
      changes or scoliosis. METHODS: A previously validated method for measuring
      permeability, based on the relaxation pressure caused by a transient-flow rate
      was used. Three specimens were extracted from each L1 to L5 endplate. Seventy-one
      specimens were frozen, and 64 were stored fresh in a standard culture media. A
      microscopic analysis completed the biomechanical analysis. RESULTS: At 2, 4, and
      6 months, the mean permeability (10(-14) m/N x s, flow-in/flow-out) of the
      central zone was respectively: 1.23/1.66, 1.03/1.29, and 0.792/1.00. Laterally,
      it was 1.03/1.19, 1.094/1.001, and 0.765/0.863. For all groups, cartilage
      endplate and growth plate were both thinner in the center of the plate. Weak
      differences of the vascular network were detected, except for a small increase of
      vascular density in the central zone. CONCLUSION: The results from this animal
      study showed that the central zone of the vertebral endplate was more permeable
      than the periphery and the flow-out permeability was up to 35% greater than the
      flow-in permeability. Increase of permeability with decrease of cartilage
      thickness was noticed within the same age group. We also found a statistically
      significant decrease of the macroscopic permeability correlated with the tissue
      maturity.

PMID- 18344855
TI  - Application of laminar screws to posterior fusion of cervical spine: measurement
      of the cervical vertebral arch diameter with a navigation system.
AB  - STUDY DESIGN: Morphometric analysis. OBJECTIVE: For safe and solid fixation, it
      is necessary to measure the diameter of the vertebral arch to ascertain whether
      or not screws can be used and if so, the appropriate size of screws to be used.
      SUMMARY OF BACKGROUND DATA: Cervical pedicle screws are the most biomechanically
      stable screws. However, their use carries a high risk of neurovascular
      complications during screw insertion. In 2004, a new method to avoid such
      vertebral artery injuries was reported by insertion of screws with crosswise to
      the lamina of C2. For safe and solid fixation, it is necessary to measure the
      diameter of the vertebral arch to ascertain whether or not screws can be used and
      if so, the appropriate size of screws to be used. There is no report of the
      diameter of the vertebral arch by a navigation system. METHODS: Morphometric
      analysis was performed on 42 patients who had undergone a CT scan of the cervical
      spine for either surgery or diagnostic purposes. To examine the possibilities to
      insert laminar screws, the diameter of the vertebral arch was measured using a
      navigation system. RESULTS: The diameter of the vertebral arch in C2 was the
      largest in the cervical spine, individual differences ranging between 0.8 and 8.4
      mm. In C2, insertion of screws with a diameter of 3 mm was possible in 80% of
      males and 63% of females. As for screws with a diameter of 4 mm, insertion was
      possible in 50% of the males and 24% of the females in C2. In C2, gender had a
      significant effect, but left-right differences and height did not. CONCLUSION:
      Laminar screws are useful as they can prevent vascular injuries, but a
      preoperative evaluation is necessary.

PMID- 18344856
TI  - Posterior atlanto-axial arthrodesis for fixation of odontoid nonunions.
AB  - STUDY DESIGN: A retrospective case series. OBJECTIVE: To determine the clinical
      and radiographic long-term results after posterior atlanto-axial arthrodesis of
      odontoid nonunions. SUMMARY OF BACKGROUND DATA: Nonunion of odontoid fractures is
      a relatively common and dreaded complication after surgical and nonoperative
      treatment of these injuries. Although there might be a significant rate, which
      require surgical stabilization due to atlanto-axial instability, only few
      publications have covered this issue and presented reliable long-term results.
      METHODS: We retrospectively analyzed the clinical and radiographic records of 9
      (4 women and 5 men) patients with an average age of 68 (42-78) years at the time
      of injury who had undergone posterior atlanto-axial arthrodesis for surgical
      treatment of odontoid nonunions between 1988 and 2004. For posterior atlanto
      axial arthrodesis, we performed either C1-C2 transarticular screw fixation, or
      posterior wiring and bone grafting, or a combination of these 2 techniques.
      RESULTS: Eight patients achieved a satisfactory clinical outcome and returned to
      their preinjury activity level. The Smiley-Webster scale showed an overall
      functional outcome score of 2.2, which was 0.9 points superior to the outcome
      score before surgery. Neurologic deficits after operative treatment of the
      odontoid nonunion were evaluated in 2 patients. In all the other patients with
      primary neurologic deficits or delayed neurologic sequelae we saw a full
      recovery. Solid bony fusion of the cervical arthrodesis was achieved in all of
      the patients. Failures of reduction or fixation were noted in 2 patients, but no
      reoperations were necessary. CONCLUSION: In summary, we had a satisfactory
      outcome after surgical treatment of odontoid nonunions in patients with atlanto
      axial instability and severe motion pain at the cervical spine. With a bony union
      rate of 100% and a noticeable improvement of clinical results and neurologic
      function, posterior atlanto-axial arthrodesis seems to be an appropriate option
      for nonunited odontoid fractures that require surgical stabilization.

PMID- 18344857
TI  - Relationship of the internal carotid artery to the anterior aspect of the C1
      vertebra: implications for C1-C2 transarticular and C1 lateral mass fixation.
AB  - STUDY DESIGN: Anatomic study of the internal carotid artery (ICA) location with
      respect to C1 based on computed tomography (CT) scans with contrast medium.
      OBJECTIVE: To measure the location of the ICA relative to the anterior aspect of
      C1 to assess the risk of placing C1-C2 transarticular or C1 lateral mass screws.
      SUMMARY OF BACKGROUND DATA: Vertebral artery injury is a known risk from
      placement of screws in C1. A previous case report revealed an ideally placed C1
      C2 transarticular screw abutting and narrowing the ICA. The risk of ICA injury
      from C1 screws is unknown. METHODS: Fifty random head and neck CT scans with
      contrast medium were retrospectively analyzed. Measurements were taken
      bilaterally including the closest distance from the ICA lumen to C1 and the
      distance from the medial edge of the ICA to a line drawn along the medial border
      of the foramen transversarium. The risk of inserting bicortical C1-C2
      transarticular and C1 lateral mass screws was estimated based on these
      measurements. RESULTS: The mean distance from the ICA to C1 was 2.88 mm on the
      left and 2.89 mm on the right. The ICA lumen was medial to the foramen
      transversarium in 42 (84%) of 50 cases (mean: 2.78 mm on the left and 3.00 mm on
      the right). The proximity of the ICA to C1 posed moderate risk in 46% of cases
      and high risk in 12% (on at least one side). CONCLUSION: Because of the risk of
      ICA injury from a drill bit or the tip of a bicortical screw, we recommend
      preoperative CT scan with contrast medium in all cases in which a screw is to be
      placed into C1. If the ICA is in close proximity to the anterior border of C1,
      unicortical fixation or a different fusion technique should be considered.

PMID- 18344858
TI  - Repeat vertebroplasty for unrelieved pain at previously treated vertebral levels
      with osteoporotic vertebral compression fractures.
AB  - STUDY DESIGN: A retrospective study was performed in patients with a repeat
      percutaneous vertebroplasty (PV) at the vertebral levels previously undergoing
      vertebroplasty. OBJECTIVE: Our purpose of this study is to examine if a repeat PV
      is effective on pain-relief at the vertebral levels previously undergoing
      vertebroplasty. SUMMARY OF BACKGROUND DATA: Although pain-relief is usually high
      with the treatment of PV in the painful osteoporotic vertebral compression
      fractures, there are still about 5% to 22% of such patients experiencing no
      improvement on pain after PV. A repeat PV at the same vertebrae previously
      treated with PV may be an option for these patients without a pain-relief.
      METHODS: Out of 334 procedures of PV in 242 patients with osteoporotic vertebral
      compression fractures from October 2000 to June 2006 in our institute, 15
      vertebrae in 15 patients with unrelieved pain in 4 to 32 days after an initial PV
      were treated with a repeat vertebroplasty. The clinical outcomes were assessed by
      measurements of visual analog scale, and the imaging features were analyzed pre-
      and postprocedure. RESULTS: The mean volume of Polymethylmethacrylate injected in
      each vertebra was 4.0 mL (range, 1.5-9 mL) in the repeat PV. During the first
      month of follow-up after repeat PV in this series, a mean visual analog scale
      scores of the pain level was reduced from 8.6 (range, 7-10) preprocedure to 1.67
      points (range, 0-4) postprocedure, with a mean reduction of 6.93 points (range, 4
      8). Complete and partial pain relief were reached in 11 (73%) and 4 patients
      (27%), respectively in a mean follow-up of 15 months. No serious complications
      related to the procedures occurred, but asymptomatic Polymethylmethacrylate
      leakage around vertebrae was demonstrated on radiograph or computed tomography in
      2 patients. CONCLUSION: The outcomes of this series suggest that repeat PV is
      effective at the same vertebral levels in patients without pain-relief who
      underwent previous PV. Absent or inadequate filling of cement in the unstable
      fractured areas of the vertebral body may be responsible for the unrelieved pain
      after the initial PV.

PMID- 18344859
TI  - Thoracolumbar flexion-distraction injuries: associated morbidity and neurological
      outcomes.
AB  - STUDY DESIGN: Retrospective study, prospectively gathered databases. OBJECTIVE:
      To assess abdominal comorbidities, missed injuries, and complications associated
      with thoracolumbar flexion-distraction injuries (FDI). SUMMARY OF BACKGROUND
      DATA: From 1989 to 2003, 153 patients with flexion-distraction type injuries were
      identified. Predominant injury mechanisms consisted of motor vehicle crashes,
      falls, and motorcycle crashes. METHODS: Spinal injuries were categorized by
      region, injury pattern, American Spinal Injury Association grade, and motor
      score. Diagnostic methods, delayed diagnoses, and complications were recorded and
      compared with variables of spinal injury, abdominal injury, and neurologic
      outcome. Treatment variables included nonoperative care, posterior surgery alone,
      anterior surgery alone, or combination treatment. Primary outcomes were
      neurologic status, unintended secondary procedures, complications, and kyphosis
      angle. RESULTS: Spinal cord injury (SCI) was found in 37 of 151 patients (25%).
      SCI was correlated with high-grade posterior element dissociation. Intra
      abdominal injury (IAI) was found in 46 of 151 of patients (30%). There was a
      statistically significant correlation between presence of FDI and IAI in the
      lumbar (L2-L4) region. There was a 3.9% incidence of delayed diagnosis of FDI and
      a 0.9% incidence of delayed diagnosis of IAI. Presence of a "lapbelt-sign" had a
      positive predictive value of 0.69 and a negative predictive value of 0.91 for
      IAI. Presence of a lumbar injury due to a motor vehicle crash in the presence of
      a lapbelt sign was positively associated with IAI. There was no increase in
      complications in the subpopulation of patients with concurrent SCI and FDI.
      CONCLUSION: Both IAI and SCI remain commonly associated with FDI of the
      thoracolumbar spinal column. The presence of an abdominal wall contusion (lapbelt
      sign) is a strong indicator of IAI. Adherence to an established trauma algorithm
      can minimize the risk of delayed diagnosis. Disruption of an established work-up
      paradigm, however, can lead to potentially life and spinal cord threatening
      complications.

PMID- 18344860
TI  - Minimal invasive short posterior instrumentation plus balloon kyphoplasty with
      calcium phosphate for burst and severe compression lumbar fractures.
AB  - STUDY DESIGN: Prospective consecutive series. OBJECTIVE: To evaluate the efficacy
      of minimal invasive surgery for acute lumbar fractures by means of balloon
      kyphoplasty with calcium phosphate plus segmental short posterior instrumented
      fusion. SUMMARY OF BACKGROUND DATA: In the surgical treatment of lumbar fractures
      with short pedicle screw instrumentation, the failure to support the anterior
      spinal column often results in loss of correction. Transpedicular augmentation
      techniques with bone and bone substitutes have been attempted whereas kyphoplasty
      has been increasingly used to augment fractured vertebral body. METHODS: Eighteen
      consecutive patients with an average age of 64 +/- 15 years, who sustained lumbar
      (L1-L4) burst and severe compression fracture were included in this prospective
      study. On admission, 2 (11%) of 18 patients had incomplete neurologic impairment.
      All patients underwent bilateral balloon kyphoplasty with calcium phosphate bone
      cement to reduce segmental kyphosis and restore vertebral body height and
      segmental pedicle screw instrumentation and fusion. Gardner kyphosis angle,
      anterior (AVBHr) and posterior vertebral body height ratio (PVBHr), and spinal
      canal encroachment (SCE) were calculated before to after surgery. VAS and SF-36
      were used to evaluate functional outcome. RESULTS: All patients were operated
      within 24 hours after admission and were followed for an average 22 months (17-28
      months) after index surgery. Operating time and blood loss averaged 45 minutes
      and 70 mL, respectively. VAS and SF-36 (role physical and bodily pain domains)
      were significantly improved after surgery. Both patients with incomplete
      neurologic lesions recovered, whereas no neurologic deterioration was observed in
      any case. Segmental kyphosis improved from an average preoperative kyphosis of 16
      to 2 degrees after surgery (P < 0.000). AVBHr improved from an average before
      surgery 0.57 to 0.87 (P < 0.000) after surgery, whereas PVBHr improved from 0.93
      before surgery to 0.98 (P < 0.05) after surgery. SCE was reduced from an average
      25% before surgery to 19% (P < 0.07) after surgery. Bone cement leakage was
      observed anteriorly to the fractured vertebral body or to the adjacent superior
      disc in 4 patients without clinical sequelae, whereas 3 pedicle screws were
      malpositioned medially to the pedicle in 3 patients without neurologic impairment
      or associated complaints. Posterolateral radiologic fusion was achieved within 6
      to 8 months after index operation. There was no instrumentation failure or loss
      of sagittal curve and vertebral height correction. CONCLUSION: Balloon
      kyphoplasty with calcium phosphate cement combined with posterior segmental short
      minimal invasive fixation for fresh burst and severe compression lumbar fractures
      provided excellent immediate reduction of post-traumatic segmental kyphosis with
      simultaneous reduction of spinal canal encroachment and restoration of vertebral
      body height in the fracture level.

PMID- 18344861
TI  - Thromboembolic disease after combined anterior/posterior reconstruction for adult
      spinal deformity: a prospective cohort study using magnetic resonance venography.
AB  - STUDY DESIGN: Thromboembolic disease (TED) after anterior/posterior spinal
      reconstructions was prospectively evaluated in 66 consecutive patients.
      OBJECTIVE: Determine the incidence of TED after anterior/posterior spinal
      reconstruction. SUMMARY OF BACKGROUND DATA: Few studies have examined the rate of
      TED after potentially high-risk combined anterior/posterior reconstructions.
      Magnetic resonance venography (MRV) is more effective at detecting pelvic deep
      venous thrombosis (DVT) than conventional screening, but has not been used in
      these patients. METHODS: We undertook a prospective cohort study of 66
      consecutive adult patients (mean, 52.7 +/- 9.6 years) undergoing combined
      anterior/posterior spinal reconstructions for spinal deformity. All patients
      received only mechanical DVT prophylaxis. After surgery, MRV and bilateral lower
      extremity Doppler ultrasounds were obtained to screen for DVT, and contrast
      enhanced spiral computed tomography scans were obtained for clinical suspicion of
      pulmonary embolism (PE). RESULTS: The total incidence of postoperative TED was
      13.6% (9 patients). The overall rate of DVT was 9.1% (6 patients), one-third
      occurring in the pelvis. PE developed in 7.6% (5 patients). In 2 patients, PE
      developed less than 48 hours after positive dopplers. In 3 patients, PE developed
      despite negative screening studies. Right-sided thoracoabdominal approaches were
      associated with an increased risk of developing DVT (P = 0.03, Odds Ratio 9.8),
      PE (P = 0.01, Odds Ratio 20), and TED (P = 0.004, Odds Ratio 12). CONCLUSION: We
      report a high rate of TED after extensive anterior/posterior spinal
      reconstructions, for which a right-sided thoracoabdominal approach is an
      independent risk factor and screening ineffective at preventing PE. These
      patients should be considered at high risk for postoperative TED.

PMID- 18344862
TI  - Morphological and functional electrophysiological evidence of relative spinal
      cord tethering in adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: Magnetic resonance (MR) imaging and multiplanar reconstruction was
      used to evaluate the morphology and relative position of the spinal cord in
      adolescent idiopathic scoliosis (AIS). OBJECTIVE: To determine the longitudinal
      and cross-sectional morphology of spinal cord in AIS subjects versus normal
      controls and their correlation with relative position of cerebellar tonsils and
      somatosensory cortical evoked potentials (SSEP). SUMMARY OF BACKGROUND DATA: Our
      previous studies revealed significantly reduced spinal cord to vertebral column
      length ratios in AIS patients with severe scoliotic curves suggesting the
      presence of disproportional growth between the neural and skeletal system. A
      possible neural origin of etiopathogenesis of AIS is suggested. METHODS: MR
      multiplanar reconstruction was performed in 97 adolescent girls (35 moderate, 26
      severe AIS with right-sided thoracic/thoracolumbar curve, and 36 age-matched
      controls). Measurements of the ratio of anteroposterior (AP) and transverse (TS)
      diameter of the cord, the concave and convex lateral cord space (LCS) were
      obtained at the apical level in AIS subjects. Same parameters were obtained in
      normal controls at matched vertebral levels. Correlations were made with cord to
      vertebral column length ratio, cerebellar tonsil position and SSEP findings.
      RESULTS: AP/TS cord ratio and LCS ratio were increased in AIS subjects in the
      presence of reduced spinal cord to vertebral length ratio when compared with
      normal controls (P < 0.05). The above ratios were exaggerated in AIS subjects
      with abnormal SSEP findings. The AP/TS cord ratio and LCS ratio were negatively
      correlated with the cord to vertebral column length ratio (rho = -0.410 and 
      0.313, P < 0.01) and cerebellar tonsillar level (rho = -0.309 and -0.432, P <
      0.01). CONCLUSION: Our study suggests presence of tethering and increased tension
      along the longitudinal axis of spinal cord with associated morphologic changes of
      cross-sectional shape and relative position of the cord.

PMID- 18344863
TI  - Comparison of observer variation in conventional and three digital radiographic
      methods used in the evaluation of patients with adolescent idiopathic scoliosis.
AB  - STUDY DESIGN: This study is a reliability analysis of coronal Cobb angle
      measurements in adolescent idiopathic scoliosis obtained by multiple observers.
      OBJECTIVE: We sought to quantify and compare the interobserver reliability of
      conventional radiographs and 3 methods of digital radiography. SUMMARY OF
      BACKGROUND DATA: The use of digital radiography for the evaluation of adolescent
      idiopathic scoliosis is being widely adopted. Previous studies comparing manual
      and computer-based measurements have found excellent intraobserver reliability
      for both techniques. Interobserver reliability of computer-based measurements on
      digital radiographs has not been compared with manual measurements on
      conventional radiographs. Other commonly used forms of output of digital
      radiography have not been studied. METHODS: Preoperative standing posteroanterior
      full-length spine radiographs from 40 patients with adolescent idiopathic
      scoliosis were examined by 4 observers. Patients were divided into 2 groups of 20
      patients. In 1 group, radiographs were obtained by conventional technique. In the
      other group, radiographs were obtained using a digital radiography system. Three
      types of output of the identical image obtained by a digital radiography system
      were examined, including computer-based image, printing of the image fitted onto
      a single film, or printing of the image onto 2 unstitched films. The Cobb angle,
      upper vertebra, and lower vertebra of the major curve were measured by each
      observer. Interobserver reliability for each technique was calculated by
      intraclass correlation coefficient and interobserver variance. RESULTS:
      Interobserver reliability as described by intraclass correlation coefficient and
      interobserver variance was excellent (0.93-0.98) for measurements made on
      conventional, computer-based, and fitted printed radiographs. The intraclass
      correlation coefficient was good (0.87) in measurements obtained on radiographs
      printed on 2 unstitched films. CONCLUSION: Measurements made on conventional and
      digital radiographs using manual and computer-based techniques have similar good
      to excellent interobserver reliability. Interobserver reliability was lower for
      digital radiographs when printed onto 2 unstitched films. The results suggest
      that different observers will obtain similar measurements when viewing the same
      image, but care should be taken when interpreting images printed on 2 unstitched
      films.

PMID- 18344864
TI  - Relationship between the histological findings of spondylolytic tissue,
      instability of the loose lamina, and low back pain.
AB  - STUDY DESIGN: We investigated the histomorphological features of the tissue
      occupying the spondylolytic defect (spondylolytic tissue), which was similar to
      ligament, and then graded the complete enthesis structure and the density of the
      fibrous portion. The relationships between the features, instability of the loose
      lamina against the affected vertebra, and the severity of low back pain were
      studied. OBJECTIVE: To elucidate the histomorphological features of spondylolytic
      tissue and the associations between the features, instability of the loose
      lamina, and low back pain. SUMMARY OF BACKGROUND DATA: Spondylolysis is thought
      to be caused primarily by a fatigue fracture and spondylolytic tissue has been
      recognized as being a fibrocartilaginous mass. Recently, innervation of the
      spondylolytic tissue was reported to be one of the sources of low back pain.
      METHODS: The spondylolytic tissue from 17 patients who underwent microscopic
      decompression of the pars defect was observed for histology including hematoxylin
      and eosin, elastica van Gieson, and immunohistochemical staining for S100
      protein. Instability of the loose lamina against the affected vertebra was
      evaluated by flexion/extension radiographs. RESULTS: The spondylolytic tissue had
      a ligamentous structure without innervation. The histomorphological findings,
      instability of the loose lamina, and low back pain had no relationship to one
      another. CONCLUSION: Spondylolysis is a pseudarthorosis of the pars
      interarticularis and the spondylolytic tissue tends to develop noninnervated
      ligament-like tissue with an enthesis structure. The histomorphological features,
      instability of the loose lamina, and low back pain have no relationship to one
      another.

PMID- 18344865
TI  - The effect of abdominal stabilization contractions on posteroanterior spinal
      stiffness.
AB  - STUDY DESIGN: Intrasubject controls with randomized intervention order.
      OBJECTIVE: To quantify the immediate change in posteroanterior (PA) spinal
      stiffness produced by different combinations of trunk muscle contraction. SUMMARY
      OF BACKGROUND DATA: The abdominal hollow and the abdominal brace are 2 different
      combinations of trunk muscle contractions that are commonly prescribed to
      increase spinal stability. Unfortunately, the immediate effect of these different
      contractions on spinal stiffness (one indicator of spinal stability) has not yet
      been quantified directly. METHODS: Twenty-eight asymptomatic subjects were taught
      abdominal hollow and brace contractions then performed them in a randomized order
      framed by periods of rest. Surface electromyography and B-mode ultrasound
      confirmed that all contractions were performed appropriately. During each test
      condition (hollow, brace, and rest), a noninvasive indentation technique was used
      to quantify PA spinal stiffness. A repeated measures analysis of variance was
      used to assess the significance of changes in the PA spinal stiffness between
      test conditions. RESULTS: Both the abdominal hollow and abdominal brace
      contractions increased PA spinal stiffness significantly when compared with the
      rest condition (P < 0.001). When the abdominal hollow and brace contractions were
      compared with each other, the abdominal brace contraction produced significantly
      greater PA spinal stiffness (P < 0.05). CONCLUSION: In asymptomatic subjects, the
      abdominal brace contraction provided an immediate PA stiffening effect that was
      significantly greater in magnitude when compared with conditions of rest and
      abdominal hollowing. These findings may allow clinicians to better match commonly
      prescribed contraction-based interventions with specific patient needs. Future
      work is required to assess the long-term effect of repeated abdominal brace and
      hollow contractions on PA spinal stiffness and low back pain.

PMID- 18344866
TI  - Lymphadenopathy of IgG4-related sclerosing disease.
AB  - IgG4-related sclerosing disease is a recently recognized syndrome characterized
      by mass-forming lesions in exocrine glands or extranodal tissues due to
      lymphoplasmacytic infiltrates and sclerosis, a raised serum IgG4 level and
      increased IgG4+ plasma cells in the involved tissues. We report the morphologic
      features of the enlarged regional (n=3) and nonregional lymph nodes (n=3) in
      patients with this syndrome. The patients presented with autoimmune pancreatitis,
      lymphoplasmacytic sclerosing cholangitis, chronic sclerosing dacryoadenitis, or
      chronic sclerosing sialadenitis. The histologic features of the lymph nodes could
      be categorized into 3 patterns: Castleman diseaselike, follicular hyperplasia,
      and interfollicular expansion by immunoblasts and plasma cells. The percentage of
      IgG4+/IgG+ plasma cells was markedly elevated (mean 62% vs. 9.9% in 54 control
      lymph nodes comprising a wide variety of reactive conditions). We also report 6
      cases of primary lymphadenopathy characterized by increased IgG4+/IgG+plasma
      cells (mean 58%). These cases share many clinical and pathologic similarities
      with IgG4-related sclerosing disease. In fact, 2 of these patients developed
      lymphoplasmacytic sclerosing cholangitis or lacrimal and submandibular gland
      involvement during the clinical course. These cases therefore probably represent
      primary lymph node manifestation of the disease. The importance of recognition of
      the lymphadenopathic form of IgG4-related sclerosing disease lies in the
      remarkable response to steroid therapy, and the potential of mistaking the
      disease for lymphoma either clinically or histologically.

PMID- 18344867
TI  - Renal translocation carcinomas: clinicopathologic, immunohistochemical, and gene
      expression profiling analysis of 31 cases with a review of the literature.
AB  - We report clinicopathologic features of a large series of renal translocation
      carcinomas from a multicentric study. Diagnosis was performed by cytogenetic
      examination of fresh material and/or by immunochemistry with antibodies directed
      against the C-terminal part of transcription factor E3 (TFE3) and native
      transcription factor EB (TFEB) proteins. Clinical data, follow-up, and histologic
      features were assessed. Antibodies against CK7, CD10, vimentin, epithelial
      membrane antigen, AE1-AE3, E-cadherin, alpha-methylacyl-coenzyme A racemase,
      melan A, and HMB45 were tested on tissue microarrays. Whole-genome microarray
      expression profiling was performed on 4 tumors. Twenty-nine cases were diagnosed
      as TFE3 and 2 as TFEB renal translocation carcinomas, including 13 males and 18
      females, mean age 24.6 years. Two patients had a previous history of chemotherapy
      and 1 had a history of renal failure. Mean size of the tumor was 6.9 cm. Thirteen
      cases were > or = pT3 stage. Twelve cases were N+ or M+. Mean follow-up was 29.5
      months. Three patients presented metastases and 5 have died. Mixed papillary and
      nested patterns with clear and/or eosinophilic cells represented the most
      consistent histologic appearance, with common foci of calcifications regardless
      of the type of translocation. Using a 30 mn incubation at room temperature, TFE3
      immunostainings were positive in only 82% of our TFE3 translocation carcinomas.
      Both TFE3 and TFEB renal translocation carcinomas expressed CD10 and alpha
      methylacyl-coenzyme A racemase in all cases. An expression of E-cadherin was
      observed in two-third of cases. Cytokeratins were expressed in less than one
      third of cases. Melanocytic markers were expressed at least weakly in all cases
      except two. Unsupervised clustering on the basis of the gene expression profiling
      indicated a distinct subgroup of tumors. TRIM 63 glutathione S-transferase A1 and
      alanyl aminopeptidase are the main differentially expressed genes for this group
      of tumors. Our results suggest that these differentially expressed genes may
      serve as novel diagnostic or prognostic markers.

PMID- 18344868
TI  - Ovarian mature teratomas with mucinous epithelial neoplasms: morphologic
      heterogeneity and association with pseudomyxoma peritonei.
AB  - Mucinous epithelial neoplasms arising in association with mature teratomas are a
      heterogeneous group of tumors, but with the exception of a single recent study,
      their full histologic spectrum, detailed immunophenotype, and association with
      classic pseudomyxoma peritonei (PMP) have not been fully studied. The
      morphologic, immunohistochemical, and clinical features of 42 patients with
      mucinous epithelial tumors arising in association with mature ovarian teratomas
      were evaluated. The patients' ages ranged from 17 to 66 years (mean, 39 y). Tumor
      size ranged from 5.5 to greater than 200 cm. Most teratoma-associated mucinous
      tumors were unilateral, although 1 patient harbored bilateral mucinous tumors in
      association with bilateral teratomas. In all cases, the teratomatous component
      consisted of mature elements. Using the 2003 World Health Organization criteria
      for ovarian intestinal type mucinous neoplasms, 17 (40%) were classified as
      mucinous cystadenoma, 16 (38%) as intestinal-type mucinous epithelial neoplasm of
      low malignant potential (IM-LMP), 4 (10%) as intraepithelial carcinoma (IEC), and
      5 (12%) as invasive mucinous carcinoma. Mucinous cystadenomas had a varied
      epithelial lining consisting of lower gastroenteric, gastric foveolar, or
      mullerian appearance. In contrast, the IM-LMP, IEC, and invasive carcinoma cases
      had a more uniform lower gastroenteric histology. For mucinous cystadenomas, a
      cytokeratin (CK) 7+/CK20- phenotype (5/13; 38%) was equally as common as a CK7
      /CK20+ phenotype (5/13; 38%), with the remaining cases coexpressing both keratins
      (CK7+/CK20+: 3/13; 23%). In contrast, IM-LMP, IEC, and invasive adenocarcinomas
      more frequently had a CK7-/CK20+ phenotype (56%, 50%, and 100%, respectively). A
      CK7+/CK20-phenotype was rare in these later 3 morphologic groups (6%). Of the 42
      total cases, 55% had pseudomyxoma ovarii and 24% had classic PMP (1 cystadenoma,
      6 IM-LMP, and 3 invasive carcinomas), whereas 5% had more localized accumulations
      of peritoneal mucin (both IM-LMP). Pathologic evaluation of the peritoneum in
      these 12 cases revealed 6 with acellular mucin alone, 3 with low-grade mucinous
      epithelium (all 3 with ovarian IM-LMP), and 3 with high-grade mucinous
      carcinomatosis (all 3 with ovarian mucinous adenocarcinoma). No appendiceal
      lesions were identified. Follow-up was available in 48% of patients (mean, 61
      mo). The only adverse outcomes occurred in the 3 patients with ovarian carcinoma
      and associated peritoneal carcinomatosis. We report that a significant proportion
      of mucinous tumors associated with mature ovarian teratomas present with clinical
      PMP, which in most cases is associated with IM-LMP. PMP in this setting may
      harbor microscopic intra-abdominal low-grade mucinous epithelium that is
      histologically and immunophenotypically similar to that typically seen in
      appendiceal-related PMP. Pseudomyxoma ovarii is common in this setting,
      particularly in tumors with IM-LMP histology, but pseudomyxoma ovarii is not
      predictive of PMP. Ovarian teratoma-associated benign and IM-LMP mucinous
      neoplasms with microscopic peritoneal low-grade mucinous epithelium do not seem
      to be at significant risk for intra-abdominal recurrence, but numbers are few and
      follow-up is limited. In contrast, teratomas with an invasive carcinomatous
      component and microscopic peritoneal carcinomatosis follow an aggressive clinical
      course.

PMID- 18344869
TI  - Psychophysical versus physiological spatial forward masking and the relation to
      speech perception in cochlear implants.
AB  - OBJECTIVES: The primary goal of this study was to determine if physiological
      forward masking patterns in cochlear implants are predictive of psychophysical
      forward masking (PFM) patterns. It was hypothesized that the normalized amount of
      physiological masking would be positively correlated with the normalized amount
      of psychophysical masking for different masker-probe electrode separations. A
      secondary goal was to examine the relation between the spatial forward masking
      patterns and speech perception performance. It was hypothesized that subjects
      with less channel interaction overall (either psychophysically or
      physiologically) would have better speech perception ability because of better
      spectral resolution. DESIGN: Data were collected for 18 adult cochlear implant
      recipients [N = 9 Clarion CII or HiRes 90K, N = 9 Nucleus 24R(CS)]. Physiological
      spatial forward masking patterns were obtained with the electrically evoked
      compound action potential (ECAP) through the implant telemetry system. PFM
      patterns were obtained using a three-interval, two-alternative forced-choice
      adaptive procedure. Both measures used a fixed probe electrode with varied masker
      location. For each subject, spatial forward masking patterns were obtained for
      three probe electrodes with five masker locations per probe. RESULTS: On an
      individual basis, the correlation between ECAP FM and PFM was strong for 10
      subjects (r = 0.68-0.85, p <or= 0.02), moderately strong for two subjects (r =
      0.54-0.55, p = 0.06-0.07), and poor for six subjects (r = 0.13-0.45, p > 0.14).
      Results across subjects and electrodes showed a highly significant correlation
      between ECAP FM and PFM (r = 0.55, p < 0.0001); the correlation was strongest for
      basal electrodes. There was no significant correlation between speech perception
      and ECAP FM or PFM. Subjects whose ECAP FM patterns correlated well with PFM
      patterns generally had the poorest speech perception and subjects with the
      poorest correlations had the best speech perception. CONCLUSIONS: ECAP FM and PFM
      patterns correlated well for two-thirds of the subjects. Although the group
      correlation was statistically significant, ECAP FM patterns only accounted for
      30% of the variance in the PFM measures. This suggests that the ECAP measures
      alone are not sufficient for accurately predicting PFM patterns for individual
      subjects.

PMID- 18344870
TI  - Music perception of cochlear implant users compared with that of hearing aid
      users.
AB  - OBJECTIVES: To investigate the music perception skills of adult cochlear implant
      (CI) users in comparison with hearing aid (HA) users who have similar levels of
      hearing impairment. It was hypothesized that the HA users would perform better
      than the CI recipients on tests involving pitch, instrument, and melody
      perception, but similarly for rhythm perception. DESIGN: Fifteen users of the
      Nucleus CI system and 15 HA users participated in a series of music perception
      tests. All subjects were postlingually deafened adults, with the HA subjects
      being required to meet the current audiological criteria for CI candidacy. A
      music test battery was designed for the study incorporating four major tasks: (1)
      discrimination of 38 pairs of rhythms; (2) pitch ranking of one-octave, half
      octave, and quarter-octave intervals; (3) instrument recognition incorporating
      three subtests, each with 12 different instruments or ensembles; and (4)
      recognition of 10 familiar melodies. Stimuli were presented via direct audio
      input at comfortable presentation levels. The test battery was administered to
      each subject on two separate occasions, approximately 4 mo apart. RESULTS: The
      results from the rhythm test were 93% correct for the CI group and 94% correct
      for the HA group; these scores were not significantly different. For the pitch
      test, there was a significant difference between the HA group and the CI group (p
      < 0.001), with higher mean scores recorded by the HA group for all three interval
      sizes. The CI subject group was unable to rank pitches a quarter-octave apart,
      only scoring at chance level for this interval size. In the instrument
      recognition test, although there was no significant difference between the mean
      scores of the two groups, both groups obtained significantly higher scores for
      the subtest incorporating single instrument stimuli than those incorporating
      multiple instrumentations (p < 0.001). In the melody test, there was a
      significant difference between the implantees' mean score of 52% correct and the
      HA group's mean of 91% (p < 0.001). CONCLUSIONS: As hypothesized, results from
      the two groups were almost identical for the rhythm test, with the HA group
      performing significantly better than the CI group on the pitch and melody tests.
      However, there was no difference between the groups in their ability to identify
      musical instruments or ensembles. The results of this study indicate that HA
      users with similar levels of hearing loss perform at least equal to, if not
      better than, CI users on these music perception tests. However, despite the
      differences between scores obtained by the CI and HA subject groups, both these
      subject groups were largely unable to achieve accurate or effective music
      perception, regardless of the device they used.

PMID- 18344871
TI  - Identification of environmental sounds with varying spectral resolution.
AB  - OBJECTIVES: This study investigated the identification of familiar environmental
      sounds with varying spectral resolution to establish (1) the number of frequency
      channels needed to perceive a large heterogeneous set of familiar environmental
      sounds, (2) the role of cross-channel asynchrony in identification performance,
      and (3) the acoustic correlates of the spectral resolution required for
      identification. DESIGN: In experiment 1, 60 normal-hearing listeners identified
      environmental sounds in a 60-alternative closed--set response task as a function
      of six spectral resolution conditions (i.e., 2, 4, 8, 16, 24, and 32 frequency
      channels) obtained with an envelope-vocoder. In experiment 2, identification
      accuracy for varying amounts of cross-channel asynchrony was determined for
      sounds with preserved and degraded fine spectral structure in 10 normal-hearing
      listeners. Experiment 3 examined identification performance of 72 listeners
      across six spectral resolution conditions as in experiment 1, but using three
      different signal processing methods designed to minimize cross-channel asynchrony
      across channels. Follow-up acoustic and discriminant analyses were carried out to
      identify parameters that can distinguish environmental sounds based on required
      spectral resolution. RESULTS: Identification accuracy tended to improve with
      increasing spectral resolution reaching the maximum of 76%. However, in
      experiment 1, performance did not change significantly beyond eight channels,
      whereas identification accuracy of some sounds declined with increasing spectral
      resolution. In experiment 2, increases in cross-channel asynchrony for sounds
      with preserved fine spectra had a small, but significant negative effect on
      identification. However, minimizing the amount of asynchrony had no significant
      effect on the overall identification of spectrally degraded sounds in experiment
      3. Acoustic analysis indicated several spectral and temporal measures that
      differed significantly between sounds that required eight or fewer channels and
      those that required 16 or more channels for 70% correct identification.
      Discriminant analysis revealed that the sounds could be classified into high- and
      low-required spectral resolution groups with 83% accuracy based on only two
      acoustic parameters: the number of bursts in the envelope and the standard
      deviation of spectral centroid velocity. CONCLUSIONS: Increasing spectral
      resolution generally had a positive effect on identification of familiar
      environmental sounds. However, across conditions performance accuracy remained
      well-below that of control stimuli with preserved fine spectra, despite becoming
      asymptotic above eight channels. Cross-channel asynchrony introduced during
      vocoder processing, although detrimental for some sounds, was not a major factor
      that prevented further improvement in overall accuracy. A spectral resolution
      greater than 32 channels, along with additional fine spectral and temporal
      information may be required for identification of a number of environmental
      sounds. This study provides a preliminary basis for optimizing environmental
      sound perception by cochlear implant users by highlighting the role of several
      acoustic factors important for environmental sound identification.

PMID- 18344872
TI  - Evaluation of an aided TEN test for diagnosis of dead regions in the cochlea.
AB  - OBJECTIVES: To compare results for the original version of the threshold
      equalizing noise [TEN(HL)] test for diagnosis of dead regions (DRs) in the
      cochlea, using stimuli presented via headphones, with results for an aided
      version of the test, the ATEN test, in which subjects listened to stimuli
      presented in free field using their own hearing aids. DESIGN: The test tones were
      warble tones for both the TEN(HL) and the ATEN test. Twenty-five subjects (12
      males and 13 females), aged between 12 and 19 yr, with severe or profound
      sensorineural hearing loss were tested. For each test, two levels of the TEN were
      used, chosen to fall within the comfortable range of levels for the individual
      subject. A DR was considered to be present when the TEN(HL) produced at least 10
      dB of masking and when the masked threshold was at least 10 dB above the nominal
      TEN(HL) level. Measurements of the outputs of the hearing aids in response to the
      TEN(HL) plus the test tones were obtained using a KEMAR acoustic manikin to
      assess the extent to which distortion or compression might have influenced the
      outcomes. RESULTS: For the TEN(HL) test, the results were often inconclusive,
      because the TEN(HL) could not be made sufficiently intense to give at least 10 dB
      of masking. The incidence of these inconclusive cases was markedly reduced for
      the ATEN test. There were more positive diagnoses of DRs for the ATEN test than
      for the TEN(HL) test. The KEMAR measurements indicated that distortion,
      compression, and/or feedback cancellation probably influenced the outcomes in
      some cases, leading to a moderate incidence of false positives for the ATEN test,
      and also some "missed" cases. CONCLUSIONS: The ATEN test leads to a lower
      incidence of inconclusive results than the TEN(HL) test in the diagnosis of DRs
      in people with severe to profound hearing loss. However, for some hearing aids
      the gain changed rapidly as a function of frequency, which undermined the
      validity of the ATEN test. Also, some hearing aids introduced distortion that
      probably affected the outcome of the test and gave misleading results. Hence, the
      ATEN test cannot be recommended for use in the clinic.

PMID- 18344873
TI  - Production and perception of speech intonation in pediatric cochlear implant
      recipients and individuals with normal hearing.
AB  - OBJECTIVES: Current cochlear implant (CI) devices are limited in providing voice
      pitch information that is critical for listeners' recognition of prosodic
      contrasts of speech (e.g., intonation and lexical tones). As a result, mastery of
      the production and perception of such speech contrasts can be very challenging
      for prelingually deafened individuals who received a CI in their childhood (i.e.,
      pediatric CI recipients). The purpose of this study was to investigate (a)
      pediatric CI recipients' mastery of the production and perception of speech
      intonation contrasts, in comparison with their age-matched peers with normal
      hearing (NH), and (b) the relationships between intonation production and
      perception in CI and NH individuals. DESIGN: Twenty-six pediatric CI recipients
      aged from 7.44 to 20.74 yrs and 17 age-matched individuals with NH participated.
      All CI users were prelingually deafened, and each of them received a CI between
      1.48 and 6.34 yrs of age. Each participant performed an intonation production
      task and an intonation perception task. In the production task, 10 questions and
      10 statements that were syntactically matched (e.g., "The girl is on the
      playground." versus "The girl is on the playground?") were elicited from each
      participant using interactive discourse involving pictures. These utterances were
      judged by a panel of eight adult listeners with NH in terms of utterance type
      accuracy (question versus statement) and contour appropriateness (on a five-point
      scale). In the perception task, each participant identified the speech intonation
      contrasts of natural utterances in a two-alternative forced-choice task. RESULTS:
      The results from the production task indicated that CI participants' scores for
      both utterance type accuracy and contour appropriateness were significantly lower
      than the scores of NH participants (both p < 0.001). The results from the
      perception task indicated that CI participants' identification accuracy was
      significantly lower than that of their NH peers (CI, 70.13% versus NH, 97.11%, p
      < 0.001). The Pearson correlation coefficients (r) between CI participants'
      performance levels in the production and perception tasks were approximately 0.65
      (p = 0.001). CONCLUSION: As a group, pediatric CI recipients do not show mastery
      of speech intonation in their production or perception to the same extent as
      their NH peers. Pediatric CI recipients' performance levels in the production and
      perception of speech intonation contrasts are moderately correlated. Intersubject
      variability exists in pediatric CI recipients' mastery levels in the production
      and perception of speech intonation contrasts. These findings suggest the
      importance of addressing both aspects (production and perception) of speech
      intonation in the aural rehabilitation and speech intervention programs for
      prelingually deafened children and young adults who use a CI.

PMID- 18344874
TI  - Frequency-specific electrocochleography indicates that presynaptic and
      postsynaptic mechanisms of auditory neuropathy exist.
AB  - OBJECTIVES: The physiological mechanisms underlying auditory neuropathy (AN)
      remain unclear and it is likely that the multiple disruptions are classified
      under the broadly defined term. Cochlear implantation is being more widely used
      in this population to bypass the suspected site-of-lesion although a number of
      cases have been identified within the Sydney Cochlear Implant Centre where this
      management strategy has been unsuccessful. It is likely that this relates to the
      different physiological mechanisms underlying AN. DESIGN: To investigate the site
      of-lesion in AN, frequency-specific round window electrocochleography (ECochG)
      was used to assess local hair-cell, dendritic, and axonal currents generated
      within the cochlea in 14 subjects with AN and compared with responses from two
      normally hearing subjects. ECochG results were then compared with electrically
      evoked auditory brain stem response (EABR) measured after cochlear implantation.
      RESULTS: The results of this study demonstrate that two dominant patterns of
      ECochG waveforms (produced by a high-frequency alternating tone burst) can be
      identified in this population of AN subjects: (a) gross waveform showing a
      prolonged summating potential (SP) latency that, in most cases, is followed by a
      small compound action potential; and (b) gross waveform showing a normal latency
      SP waveform followed by a broad negative potential [assumed to reflect the
      dendritic potential (DP) identified in anaesthetized guinea-pigs]. This study
      demonstrates that in most subjects (n = 7) with a prolonged latency SP but no DP,
      normal morphology EABR waveforms were elicited for all electrode channels. On the
      other hand, all subjects (n = 7) who showed a normal latency SP followed by a
      broad negative DP, showed EABR waveforms that were absent or having poor wave V
      morphology. The authors' interpretation of this is that ECochG results may
      provide a classification of AN into pre- and postsynaptic lesions. CONCLUSIONS:
      We suggest that a presynaptic and postsynaptic type of AN exist that may have
      implications for the fitting of cochlear implants.

PMID- 18344875
TI  - Sex work and HIV status among transgender women: systematic review and meta
      analysis.
AB  - BACKGROUND: Transgender women are a key risk group for HIV, and epidemiologic
      studies have attributed high rates of HIV infection to behaviors associated with
      sex work in this population. This systematic review compared HIV prevalence among
      transgender female sex workers (TFSWs) with prevalence among transgender women
      who do not engage in sex work, male sex workers, and biologically female sex
      workers. METHODS: We conducted systematic searches of 6 electronic databases, and
      including studies that met pre-established criteria. We extracted data, appraised
      methodologic quality, assessed heterogeneity, and organized meta-analyses by
      comparison group. RESULTS: We identified 25 studies among 6405 participants
      recruited from 14 countries. Overall crude HIV prevalence was 27.3% in TFSWs,
      14.7% in transgender women not engaging in sex work, 15.1% in male sex workers,
      and 4.5% in female sex workers. Meta-analysis indicated that TFSWs experienced
      significantly higher risk for HIV infection in comparison to all other groups
      (relative risk [RR] = 1.46, 95% confidence interval [CI]: 1.02 to 2.09), and
      particularly in comparison to female sex workers (RR = 4.02, 95% CI: 1.60 to
      10.11). We observed significant heterogeneity among the included studies, along
      with methodologic limitations and imprecise definitions of sex work and gender.
      CONCLUSIONS: TFSWs could benefit from targeted HIV prevention interventions, HIV
      testing, and interventions to help reduce the risk of contracting or transmitting
      HIV. Structural interventions to reduce reliance on sex work among transgender
      women may be warranted.

PMID- 18344876
TI  - Drug-specific effect of nelfinavir and stavudine on primary culture of human
      preadipocytes.
AB  - Lipodystrophic syndrome is a major side effect of antiviral therapy leading to
      profound disturbances in adipose tissue. Human preadipocyte primary culture
      represents a model to understand mechanisms by which antiretroviral drugs alter
      adipocyte biology. The aim of this study was to evaluate the effects of various
      protease and nucleoside reverse transcriptase inhibitors in this model. We tested
      the effect of drugs on triglyceride accumulation and expression of specific genes
      by real-time polymerase chain reaction. To determine differential mechanisms by
      which the efficient drugs operate, we studied mitochondrial effects by evaluating
      oxygen consumption rates and nuclear lamina alteration by immunocytology. Only
      stavudine and nelfinavir, both at 10 microM, altered human adipose cell
      differentiation, as shown by reduced triglyceride accumulation. Our studies
      revealed that stavudine increased expression of genes such as PGC1 and LPL and
      affected mitochondrial respiration. Cells treated with nelfinavir had a lower
      expression of PPARgamma, LPL, and ap2 and presented disorganization of lamin A/C.
      Our data suggest for the first time in a model of human adipocytes differentiated
      in vitro that stavudine and nelfinavir interfere with the process of
      differentiation by 2 distinct mechanisms. This may be particularly relevant in
      understanding the physiopathologic mechanisms underlying the lipodystrophic
      syndrome.

PMID- 18344877
TI  - Association of HIV infection and HIV/HCV coinfection with C-reactive protein
      levels: the fat redistribution and metabolic change in HIV infection (FRAM)
      study.
AB  - OBJECTIVE: Inflammation is a potential mechanism to explain the accelerated
      atherosclerosis observed in HIV- and hepatitis C virus (HCV)-infected persons. We
      evaluated C-reactive protein (CRP) in HIV-infected and HIV/HCV-coinfected
      individuals in the era of effective antiretroviral (ARV) therapy. DESIGN: Cross
      sectional study of Fat Redistribution and Metabolic Change in HIV Infection
      (FRAM) cohort and controls from the Coronary Artery Risk Development in Young
      Adults (CARDIA) study. METHODS: CRP levels were measured in 1135 HIV-infected
      participants from the FRAM cohort and 281 controls from the CARDIA study. The
      associations of HIV and HIV/HCV infection with CRP levels were estimated by
      multivariable linear regression. RESULTS: Compared with controls, HIV
      monoinfection was associated with an 88% higher CRP level in men (P < 0.0001) but
      with no difference in women (5%; P = 0.80) in multivariate analysis. CRP levels
      were not associated with ARV therapy, HIV RNA level, or CD4 cell count. Compared
      with controls, HIV/HCV coinfection was associated with a 41% lower CRP level in
      women (P = 0.012) but with no difference in men (+4%; P = 0.90). Among HIV
      infected participants, HCV coinfection was associated with 50% lower CRP levels
      after multivariable analysis (P < 0.0001) in men and women. Greater visceral
      adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were strongly
      associated with CRP levels. Among HIV-infected participants, CRP levels were 17%
      (P < 0.001) and 21% (P = 0.002) higher per doubling of VAT and SAT; among
      controls, CRP levels were 34% (P < 0.001) and 61% (P = 0.009) higher,
      respectively. CONCLUSIONS: In the absence of HCV coinfection, HIV infection is
      associated with higher CRP levels in men. HCV coinfection is associated with
      lower CRP levels in men and women.

PMID- 18344878
TI  - Reduced mortality associated with breast-feeding-acquired HIV infection and
      breast-feeding among HIV-infected children in Zambia.
AB  - OBJECTIVES: In developing countries, where mother-to-child transmission of HIV
      through breast-feeding is common, little is known about the impact of postpartum
      transmission on child survival. This study assessed whether children infected
      postpartum have longer survival from time of infection versus those infected
      during gestation or delivery. DESIGN: We used a prospective cohort study to
      analyze data from 213 HIV-infected children enrolled in a breast-feeding
      intervention trial in Lusaka, Zambia (2001 to 2004). METHODS: We compared
      mortality 1 year after HIV infection in children stratified by age of infection:
      0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum
      [IP/EPP] group), and >40 days (postpartum [PP] group). RESULTS: A total of 61,
      71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively.
      Children with intrauterine or intrapartum/early postpartum transmission had
      higher mortality over the first 12 months after infection than children with
      postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences
      were detected between children with intrauterine and intrapartum/early postpartum
      transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after
      infection, whereas nearly 10% of the PP group had died by this time. After
      adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal
      death, children infected postpartum had one quarter the mortality rate (hazard
      ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected
      in utero. Stopping breast-feeding increased mortality in infected children (HR =
      3.1, 95% CI: 1.8 to 5.3). CONCLUSIONS: This study demonstrates a survival benefit
      among children infected postpartum versus children infected during pregnancy or
      delivery and a benefit to increased breast-feeding duration among infected
      children. Testing children for HIV early may provide a means to allow for earlier
      intervention.

PMID- 18344879
TI  - Prevention of mother-to-child transmission of HIV-1 through breast-feeding by
      treating infants prophylactically with lamivudine in Dar es Salaam, Tanzania: the
      Mitra Study.
AB  - OBJECTIVE: To investigate the possibility of reducing mother-to-child
      transmission (MTCT) of HIV-1 through breast-feeding by prophylactic
      antiretroviral (ARV) treatment of the infant during the breast-feeding period.
      DESIGN: An open-label, nonrandomized, prospective cohort study in Tanzania
      (Mitra). METHODS: HIV-1-infected pregnant women were treated according to regimen
      A of the Petra trial with zidovudine (ZDV) and lamivudine (3TC) from week 36 to 1
      week postpartum. Infants were treated with ZDV and 3TC from birth to 1 week of
      age (Petra arm A) and then with 3TC alone during breast-feeding (maximum of 6
      months). Counseling emphasized exclusive breast-feeding. HIV transmission was
      analyzed using the Kaplan-Meier survival technique. Cox regression was used for
      comparison with the breast-feeding population in arm A of the Petra trial, taking
      CD4 cell count and other possible confounders into consideration. RESULTS: There
      were 398 infants included in the transmission analysis in the Mitra study. The
      estimated cumulative proportion of HIV-1-infected infants was 3.8% (95%
      confidence interval [CI]: 2.0 to 5.6) at week 6 after delivery and 4.9% (95% CI:
      2.7 to 7.1) at month 6. The median time of breast-feeding was 18 weeks. High
      viral load and a low CD4 T-cell count at enrollment were associated with
      transmission. The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in
      infants who were HIV-negative at 6 weeks was 1.2% (95% CI: 0.0 to 2.4). The
      cumulative HIV-1 infection or death rate at 6 months was 8.5% (95% CI: 5.7 to
      11.4). No serious adverse events related to the ARV treatment of infants
      occurred. The HIV-1 transmission rate during breast-feeding in the Mitra study up
      to 6 months after delivery was more than 50% lower than in the breast-feeding
      population of Petra arm A (relative hazard=2.61; P=0.001; adjusted values). The
      difference in transmission up to 6 months was significant also in the
      subpopulation of mothers with CD4 counts>or=200 cells/microL. CONCLUSIONS: The
      rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery
      are among the lowest reported in a breast-feeding population in sub-Saharan
      Africa. Prophylactic 3TC treatment of infants to prevent MTCT of HIV during
      breast-feeding was well tolerated by the infants and could be a useful strategy
      to prevent breast milk transmission of HIV when mothers do not need ARV treatment
      for their own health.

PMID- 18344880
TI  - Gastric perforation with an associated subhepatic liver abscess related to an
      accidentally ingested lobster shell.

PMID- 18344881
TI  - Oral metastatic cancers from hepatocellular carcinoma.

PMID- 18344882
TI  - Hemolytic-uremic syndrome associated with gemcitabine treatment for metastatic
      pancreatic cancer.

PMID- 18344883
TI  - Complete remission of severe scleritis and psoriasis in a patient with active
      Crohn's disease using Modulen IBD as an exclusive immunomodulating diet.

PMID- 18344884
TI  - Management of occluded uncovered metallic stents in patients with malignant
      distal biliary obstructions using covered metallic stents.
AB  - BACKGROUND: Self-expandable metallic stents (EMSs) have been widely used for the
      palliative treatment of unresectable malignant biliary obstructions, but EMSs are
      often occluded owing to tumor ingrowth via the wire mesh. Currently, there is no
      consensus on the management of occluded EMSs. We evaluated the efficacy of a
      covered EMS as a second endoprosthesis in patients with an occluded EMS. METHODS:
      Forty patients with an occluded uncovered EMS (14 men, 26 women; mean age 72 y,
      range 41 to 89 y) were studied. The patients suffered from the following:
      pancreatic cancer in 18, bile duct cancer in 11, gallbladder cancer in 5, lymph
      node metastasis in 4, and papillary cancer in 2. Of these, 26, 7, and 7 were
      treated with a covered EMS, an uncovered EMS, and a plastic stent (PS),
      respectively. The second stent was inserted as a stent-in-stent. RESULTS: The
      mean patent period for the covered EMS was 220 days, whereas the mean patent
      periods for the uncovered EMS and plastic stent were 141 and 58 days,
      respectively. The cumulative patency of the covered EMS group was significantly
      higher (P=0.0404) than that of the uncovered EMS group. No significant
      differences in survival were observed between the covered and uncovered groups.
      No serious complications occurred. CONCLUSION: Insertion of a covered EMS is an
      effective and safe treatment for an occluded uncovered EMS.

PMID- 18344885
TI  - Changes in liver histology as a "surrogate" end point of antiviral therapy for
      chronic HBV can predict progression to liver complications.
AB  - BACKGROUND: The modified histology activity index (HAI) score has been
      extensively used as an additional primary or secondary end point in most phase
      III pivotal therapeutic clinical trials on chronic hepatitis B. Improvement in
      modified HAI after antiviral therapy has usually been defined as a 2-point
      reduction in modified HAI score. AIM: We studied whether a 2-point change in
      modified HAI score after antiviral therapy for chronic hepatitis B is associated
      with progression to liver complications (decompensated cirrhosis or
      hepatocellular carcinoma). METHOD: Eighty-nine patients treated with interferon
      alpha with liver biopsy before and at 6 to 12 months after the end of therapy
      were followed-up for a median 119.4 months. RESULTS: At the time of analysis, 11
      patients (12.4%) had liver complications. Liver complications were higher in
      patients with a 2-point increase in modified HAI score [8 of 19 patients (42.1%)
      vs. 3 of 70 patients (4.3%), P=0.0002] and in those with severe fibrosis at end
      of therapy [6 of 19 patients (31.6%) vs. 5 of 70 patients (7.1%), P=0.010]. On
      Cox regression analysis, a 2-point increase in modified HAI score was associated
      with increased liver complications (relative risk 5.564, P=0.036). CONCLUSIONS: A
      2-point increase in modified HAI score after antiviral therapy is associated with
      increased progression to liver complications.

PMID- 18344886
TI  - A double-blind, placebo-controlled, randomized study of infliximab in primary
      sclerosing cholangitis.
AB  - GOALS: To evaluate the safety and efficacy of infliximab in patients with primary
      sclerosing cholangitis. STUDY: In this double-blind, placebo-controlled study, 24
      patients with primary sclerosing cholangitis were screened and randomly assigned
      in a 2:1 ratio to receive infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, 12,
      18, and 24; patients were followed through week 52. The primary efficacy end
      point was a decrease of at least 50% in the serum alkaline phosphatase level from
      baseline to week 18. A blinded histologic assessment of liver biopsy samples,
      obtained at weeks 0 and 26, was performed using a predefined scoring system,
      including scores for inflammation, fibrosis, and cholestasis. RESULTS: Patient
      enrollment was prematurely stopped when results of an interim analysis showed no
      significant treatment benefit. Of the 24 patients screened, 10 were enrolled (6
      patients received infliximab). Mean alkaline phosphatase levels at weeks 0, 18,
      and 52 were 349, 330, and 389 U/L, respectively, for the infliximab group and
      481, 438, and 391 U/L, respectively, for the placebo group. Liver biopsy samples
      were analyzed in 7 patients (4 infliximab); no apparent differences could be
      detected in any of the histologic parameters. In 3 of 4 infliximab-treated
      patients and 2 of 3 placebo-treated patients, the disease stage did not change
      after 6 months of treatment. No meaningful changes were detected in the symptom
      score. No serious drug-related adverse events were observed. CONCLUSIONS: Study
      findings failed to demonstrate efficacy of infliximab in this small group of
      patients with established primary sclerosing cholangitis.

PMID- 18344887
TI  - Adjuvant therapeutic plasma exchange in liver failure: assessments of clinical
      and laboratory parameters.
AB  - BACKGROUND: Therapeutic plasma exchange (TPE) seems to be an effective approach
      for clearing toxins, immune-mediated antigens, and other particles from the
      circulation. The aim of this study was to analyze the positive effects of TPE on
      clinical and biochemical parameters of liver failure. PATIENTS AND METHODS:
      Between January 2001 and March 31, 2005 individuals (men/women, 17/14; median
      age, 42.7+/-15.8 y) with acute and chronic liver failure who underwent a total of
      113 TPEs (median session 3.7) were retrospectively reviewed. TPE was performed
      using the Fresenius AS-TEC 204 cell separator (Fresenius AG, Germany). The
      indication for TPE was severe coagulopathy (prothrombin time >20 s), severe
      hepatic encephalopathy, hyperbilirubinemia, and candidacy for liver
      transplantation. All patients were examined before and immediately after the last
      TPE session. RESULTS: When compared with baseline, there was significant
      improvement in hepatic encephalopathy stage (from median score 3.0 to 1.0,
      P=0.001), serum prothrombin time (from median 26.0 to 20.0 s, P=0.003),
      aminotransferases (P<0.001), and total bilirubin levels (from median 35.0 to 23.3
      mg/dL, P<0.001) after TPE. Thirteen of the thirty-one individuals (41.9%) died in
      the hospital. The mean follow-up period of 18 survival patients was 35.9+/-5.6
      months and 10 of those survived (55.6%, 10/18). No serious adverse effect of TPE
      was observed in any of the patients during or after completion of TPE. Only 6
      patients experienced minor transfusion reactions. CONCLUSIONS: TPE seems to be
      effective in improving hepatic encephalopathy stage and liver tests in
      individuals with acute and chronic liver failure. The data suggest that TPE is
      safe and tolerable in such individuals, however, overall survival remains poor
      despite TPE.

PMID- 18344888
TI  - Transjugular intrahepatic portosystemic shunt versus endoscopic therapy in the
      secondary prophylaxis of variceal rebleeding in cirrhotic patients: meta-analysis
      update.
AB  - GOALS: The aim of this study was to determine through meta-analysis the effects
      of transjugular intrahepatic portosystemic shunt (TIPS) for the reduction of
      variceal rebleeding (VRB). BACKGROUND: Variceal bleeding is one of the most
      frequent and severe complications of chronic liver disease. Although prophylactic
      use of TIPS for the reduction of VRB has been evaluated, the discrepancy about
      TIPS's beneficial effect on cirrhotic patients still exists. STUDY: We employed
      the method recommended by the Cochrane Collaboration to perform a meta-analysis
      of randomized controlled trials (RCTs) of TIPS versus endoscopic therapy in the
      prevention of VRB including 12 RCTs conducted in 7 different countries. RESULTS:
      Most RCTs reviewed were of high quality. The updated meta-analysis showed that
      the decreased incidence of VRB [odds ratio (OR)=0.32, 95% confidence interval
      (CI) (0.24-0.43), P<0.00001], deaths due to rebleeding [OR=0.35, 95% CI (0.18
      0.67), P=0.002], the increased rate of posttreatment encephalopathy [OR=2.21, 95%
      CI (1.61-3.03), P<0.00001] were correlated with TIPS, whereas the hospitalization
      days [weighted mean difference=-0.21, 95% CI (-3.50 to 3.08), P=0.90] and deaths
      due to all causes [OR=1.17, 95% CI (0.85-1.61), P=0.33] returned negative results
      in 2 groups. CONCLUSIONS: TIPS is currently the first choice to prevent
      rebleeding except that TIPS is worse than endoscopic therapy for encephalopathy.
      An exploration of new approaches out of above complications will be of
      considerable clinical significance and be a challenge to clinicians.

PMID- 18344889
TI  - Endoscopic diagnosis and treatment of pancreatic cysts.
AB  - Pancreatic cystic neoplasms have emerged as an important new opportunity for many
      disciplines to participate in the diagnosis and management of early pancreatic
      neoplasia. With an increase in an understanding of these lesions and their
      potential for malignant transformation, there has been a dramatic increase in the
      frequency of diagnosis. We critically examined the literature on diagnostic
      methods for pancreatic cystic lesions over the past 5 years. The methods of
      endoscopic pancreatic pseudocyst drainage and clinical outcomes are also
      discussed. Morphologic studies of cystic lesions using cross-sectional imaging or
      endoscopic ultrasound have a low diagnostic rate. Cyst fluid analysis with the
      use of tumor markers (eg, carcinoembryonic antigen) increases the accuracy of
      diagnosis. The management of cystic lesions is heavily dependent on the type of
      cyst, the neoplastic potential, and the risk of surgery. The traditional therapy
      is pancreatic resection and not cyst enucleation. In contrast to cystic
      neoplasms, pseudocysts are localized collections of inflammatory fluid that mimic
      cystic neoplasms. The fluid collections arise from chronic pancreatitis and
      ductal leaks. Because pseudocysts have no neoplastic potential, they can be
      drained rather than resected. Drainage can be safely accomplished with external
      catheters or endoscopically with internal catheters. As we learn more about the
      pathophysiology of the various cystic lesions, treatment will be tailored to the
      specific cyst lesion. Endoscopic ultrasound has an important role in the
      characterization of pancreatic cystic lesions and helps in selection of the
      optimal treatment modality.

PMID- 18344890
TI  - A nationwide survey evaluating adherence to guidelines for follow-up after
      polypectomy or treatment for colorectal cancer.
AB  - BACKGROUND: Endoscopic follow-up (FU) in patients treated for colorectal adenomas
      or cancer (CRC) is intended to reduce the incidence of CRC. In the Dutch
      postpolypectomy guidelines, the FU interval is solely determined by the number of
      previous adenomas, whereas in other countries size and histology are also taken
      into account. Whether this difference in policy is also reflected in clinical
      practice is unknown. Furthermore, FU guidelines after CRC are not standardized in
      The Netherlands, even though national recommendations are available. GOAL: To
      assess the adherence to the current Dutch postpolypectomy guidelines and to
      evaluate the FU policy after CRC resection. STUDY: A survey was sent to all
      Gastrointestinal Departments in The Netherlands. The survey consisted of
      questions on logistic organization of FU, postpolypectomy FU intervals, and FU
      after CRC. RESULTS: The response rate was 85%. In contrast to the national
      guidelines, size and histology of the adenomas were often taken into account,
      leading to shortening of the FU interval. With respect to the CRC cases, 52% of
      the respondents advised shorter FU intervals than advised by the national
      recommendations. CONCLUSIONS: Despite recent Dutch postpolypectomy guidelines,
      clinicians incorporate histology and size into their clinical strategy. Either
      further education on the guidelines is needed, or the guidelines need to be
      reconsidered. Furthermore, evidence-based guidelines for FU after CRC should be
      formulated.

PMID- 18344891
TI  - Hyperhomocysteinemia in inflammatory bowel disease patients without past
      intestinal resections: correlations with cobalamin, pyridoxine, folate
      concentrations, acute phase reactants, disease activity, and prior thromboembolic
      complications.
AB  - OBJECTIVE: Homocysteine is a sulfur-containing amino acid formed during the
      demethylation of methionine and high levels of this amino acid is a known risk
      factor for both arterial and also venous thromboembolic complications.
      Deficiencies of cobalamin, folate, and pyridoxine may predispose subjects to
      hyperhomocysteinemia, a common phenomenon in inflammatory bowel disease (IBD)
      patients. The aim of this study was to identify the prevalence, risk factors of
      hyperhomocysteinemia and its correlation with prior thromboembolic events in an
      IBD cohort without past intestinal resections. METHODS: In this prospective
      study, we studied the concentrations of homocysteine, cobalamin, folate, and
      pyridoxine in 105 consecutive patients with IBD, of whom 11 had a prior history
      of thromboembolic complications. Data regarding smoking habits, medication use,
      disease location, and severity were gathered and patients with past intestinal
      resections were excluded. Age-matched and sex-matched 85 healthy volunteers
      served as controls and multivariate regression analysis was performed to find out
      independent predictors of hyperhomocysteinemia. RESULTS: The mean age (+/-SD) in
      the IBD cohort was 38.69+/-12.13 years, and 51% were male. The mean age in the
      control group was 37.61+/-10.05 years, and 52% were male. Homocysteine
      concentrations in patients were higher [16.35 micromol/L (range 6.82 to 48.15)
      vs. 9.60 micromol/L (range 4.97 to 17.39), P=0.000] and hyperhomocysteinemia had
      a higher prevalence in patients than in the controls (56.2% vs. 4.7%,
      chi2=56.179, P=0.000), thus IBD significantly increased the risk of
      hyperhomocysteinemia [odds ratio=25.973 (95% confidence interval: 8.861-76.128)].
      Homocysteine concentrations in patients with a history of thrombosis were not
      higher than those without a history of thrombosis [16.29 micromol/L (range 8.45
      to 34.75) vs. 16.36 micromol/L (range 6.82 to 48.15), not significant].
      Hyperhomocysteinemia was found in 54.5% of patients with thrombosis and 56.4% of
      patients without thrombosis (not significant). On stepwise regression analysis,
      plasma cobalamin level, albumin concentration, erythrocyte sedimentation rate,
      and platelet count were found to be independent predictors of elevated
      homocysteine levels. CONCLUSIONS: IBD patients have a higher prevalence of
      hyperhomocysteinemia than do healthy controls and elevated homocysteine levels
      are independently associated with lower serum cobalamin, albumin levels and
      elevated erythrocyte sedimentation rate, and platelet count. There is no
      correlation between hyperhomocysteinemia and a history of prior thromboembolic
      events.

PMID- 18344892
TI  - Clinical significance of colonoscopic findings associated with colonic thickening
      on computed tomography: is colonoscopy warranted when thickening is detected?
AB  - GOAL: To determine the utility of colonoscopy in the management of patients with
      abdominal pain found to have colonic thickening on computed tomography (CT).
      BACKGROUND: CT is often used in the investigation of abdominal pain. Clinical
      guidelines regarding colonoscopy when colonic wall thickening is reported at CT
      are lacking. STUDY: From July 2000 to April 2004, the abdominal CT reports of all
      patients at a major teaching hospital who were investigated for abdominal pain
      were reviewed. Cases were selected if any colonic wall thickening was reported.
      Patients were excluded if they had a previously diagnosed gastrointestinal
      condition, or if they had not undergone colonoscopy within 30 days of the
      abnormal CT. Clinical, endoscopic, and pathologic data were extracted from the
      medical records of all eligible patients. RESULTS: One hundred seven cases were
      identified. Of these, 8 (7.4%) had colorectal adenocarcinoma. In 10 patients
      (9.3%), a new diagnosis of inflammatory bowel disease (IBD) was made. Sixteen
      (15.0%) had findings consistent with infectious colitis, 39 (36.4%) ischemic
      colitis, and 6 patients (5.6%) had miscellaneous findings possibly responsible
      for the colonic thickening (diverticulitis, appendicitis, proctitis, and
      melanosis coli). In 28 patients (26.1%), no abnormality was found that could
      explain the CT finding. Of those diagnosed with colorectal carcinoma or IBD, only
      4 of the 18 patients (28%) presented with evidence of gastrointestinal bleeding
      or anemia. CONCLUSIONS: On the basis of the rate of new diagnoses of colorectal
      carcinoma and IBD, we recommend colonoscopy be performed after clinical
      evaluation in patients with abdominal pain and colonic thickening on CT.

PMID- 18344893
TI  - High prevalence of celiac disease in Mexican Mestizo adults with type 1 diabetes
      mellitus.
AB  - BACKGROUND AND AIMS: Recent studies have shown that celiac disease (CD) could
      affect 0.5% to 3% of the general population, including Mexican Mestizos, which
      represents a complex mixture of genetics, and constitutes the core of Mexican and
      Latin American populations. However, the association between CD and other
      conditions, specifically type-1 diabetes mellitus, in this population remains
      unknown. Thus, our aim was to determine the prevalence of both serologic and
      biopsy proven CD in Mexican Mestizo adults with type-1 diabetes. METHODS: Over a
      6-month period, serum samples obtained from consecutive Mexican Mestizo adult
      patients (age >or=18 y) with type-1 diabetes were tested with a new generation
      human recombinant protein based IgA tissue transglutaminase enzyme-linked
      immunosorbent assay commercial kit. All patients with positive serologic test
      results underwent upper gastrointestinal endoscopy and small intestinal biopsies
      to confirm CD. RESULTS: Eighty-four type-1 diabetic patients were included (62
      women, mean age 28.9+/-9 y). Overall, 9 patients (9/84) were positive for IgA
      tissue transglutaminase with a point prevalence of 10.7% (95% CI, 4%-17%). Seven
      patients agreed to undergo endoscopy. Five subjects had biopsy-proven CD (5.9%,
      95% CI, 1.9%-13.3%). One patient had chronic diarrhea and other abdominal
      bloating; whereas the remaining 3 were asymptomatic. CD associated type-1
      diabetic patients tended to have higher hemoglobin A1c levels (P=0.07),
      reflecting poor glycemic control. CONCLUSIONS: As in other populations, we
      demonstrated a high prevalence of biopsy-proven CD (5.9%) among Mexican Mestizo
      patients with type-1 diabetes. Clinicians should be aware of this common
      association in this ethnic group.

PMID- 18344894
TI  - A novel classification scheme for gastroparesis based on predominant-symptom
      presentation.
AB  - AIM: Symptoms of gastroparesis are very diverse. Classifying patients by
      predominant symptom may improve management strategy. GOAL: To validate a new
      symptom-predominant classification for gastroparesis using symptom severity and
      quality-of-life measures. STUDY: Subjects with gastroparesis for >2 months were
      prospectively enrolled. A physician classified each subject into one of the
      following: vomiting-predominant, dyspepsia-predominant, or regurgitation
      predominant gastroparesis. Subjects also classified themselves independently from
      the physician. Each subject completed a Patient Assessment of Gastrointestinal
      Disorders-Symptom Severity Index (PAGI-SYM) and SF-12v2 Health-Related Quality-Of
      Life survey. Receiver operating characteristic curves were constructed with
      sensitivity and specificity of each PAGI-SYM subscale to differentiate subjects
      into symptom-predominant subgroups. Area under the curve (AUC) was used to
      compare the receiver operating characteristic curves. Analysis of variance,
      Cohen's kappa (kappa) statistic, student t test, and Pearson correlation (r) were
      used. RESULTS: One hundred subjects (87 females, mean 48 y) were enrolled. There
      was a 78% concordance between physician and subject's classification of
      gastroparesis with substantial correlation (kappa=0.64). PAGI-SYM nausea/vomiting
      subscale (AUC=0.79) and PAGI-SYM heartburn/regurgitation subscale (AUC=0.73) were
      the best in differentiating subjects into vomiting-predominant and regurgitation
      predominant gastroparesis, respectively. No subscale was adequate to
      differentiate dyspepsia-predominant gastroparesis. SF-12v2 total scores
      significantly correlated with worsening of the total PAGI-SYM scores (r=-0.339 to
      -0.600, all P<0.001). CONCLUSIONS: There was a substantial agreement between
      physician and patient using a symptom-predominant gastroparesis classification.
      Results suggest that a predominant-symptom classification is a valid means to
      categorize subjects with vomiting-predominant and regurgitation-predominant
      gastroparesis. Patients with dyspepsia and delayed gastric emptying need further
      research.

PMID- 18344895
TI  - Helicobacter pylori infection and development of gastric cancer in Korea: long
      term follow-up.
AB  - BACKGROUND AND AIM: Infection of Helicobacter pylori is viewed as a major driver
      of progression to the precancerous state or to gastric cancer. This study was
      performed to investigate the effect of H. pylori infection on gastric cancer
      development and to determine to what extent H. pylori eradication is likely to
      reduce the prevalence of gastric cancer. METHODS: Gastric cancer development was
      investigated in 1790 Korean subjects who underwent gastroscopy and H. pylori
      testing between 1992 and 1998. The effects of H. pylori-positive and eradicated
      states on gastric cancer development were analyzed. RESULTS: Gastric cancer
      developed in 5 of the study cohort during a mean follow-up period of 9.4 years.
      All of these patients were positive for H. pylori infection, and 4 of the 5 had
      antral intestinal metaplasia (IM) at the time of study enrollment. One of these 5
      patients was in an eradicated state when the gastric cancer was diagnosed, and
      had histologic IM before eradication therapy was performed. Gastric cancer was
      found to develop 10.9 times more frequently in the presence of IM than in its
      absence. CONCLUSIONS: The present study shows a close relationship between H.
      pylori infection and IM, and between IM and the development of gastric cancer. In
      addition, our finding suggests that chronic H. pylori infection looks like an
      important risk factor for the development of gastric cancer in Korea, where the
      prevalence of H. pylori remains high. This study indicates that to prevent
      gastric cancer H. pylori eradication is best performed before the development of
      IM.

PMID- 18344896
TI  - Effect of proton-pump inhibitor treatment on symptoms and quality of life in GERD
      patients depends on the symptom-reflux association.
AB  - BACKGROUND: Gastroesophageal reflux disease patients demonstrate various
      pathophysiologic backgrounds. Therefore, a heterogeneous response to proton-pump
      inhibitor (PPI) treatment can be expected. We investigated the effect of short
      term PPI treatment on symptoms and quality of life (QOL) in primary care patients
      with and without pathologic esophageal acid exposure and in presence or absence
      of a positive association between symptoms and reflux episodes. STUDY: Seventy
      four heartburn patients were categorized into 4 groups according to positive or
      negative symptom-reflux association, as expressed in symptom index, symptom
      sensitivity index, and symptom association probability (SAP) and presence or
      absence of pathologic reflux, defined as esophageal pH<4%>6% of the time (pH+/pH
      ). Overall and specific reflux symptoms were assessed 1 week before and the last
      week during a 2-week course of 40-mg esomeprazole daily. The QOL was scored by
      the Quality of Life in Reflux and Dyspepsia questionnaire 2 weeks before
      treatment and directly after. RESULTS: Using the SAP to assess symptom-reflux
      associations, the 4 groups [SAP+pH+(n=40); SAP+pH-(n=12); SAP-pH+(n=10); SAP-pH
      (n=10)] had similar demographic characteristics. The SAP-pH- subgroup had the
      least overall symptom reduction (P<0.01) and in the SAP+pH+ subgroup the greatest
      heartburn symptom reduction was found (P<0.02). The residual symptom scores on
      treatment were lowest in SAP+pH+ and highest in SAP-pH- subgroups and relatively
      high in the SAP+pH-. QOL was severely reduced and SAP-pH- patients had the lowest
      QOL overall. Similar findings were made using symptom index and symptom
      sensitivity index. CONCLUSIONS: Symptomatic reflux patients without evidence of
      reflux disease on a 24-hour pH recording responded less favorably to PPI
      treatment than patients with a positive symptom-reflux association or with
      pathologic reflux.

PMID- 18344897
TI  - As the stomach churns--or not!

PMID- 18344898
TI  - Transjugular intrahepatic portosystemic shunt (TIPS): its time has come.

PMID- 18344900
TI  - Structure of obsessive-compulsive symptoms in pediatric OCD.
AB  - OBJECTIVE: It is unclear whether the structure of obsessive-compulsive disorder
      (OCD) symptoms seen in adults is preserved in pediatric samples. METHOD: A total
      of 238 children and adolescents referred to a specialty pediatric OCD clinic were
      administered the Children's Yale-Brown Obsessive Compulsive Scale Symptom
      Checklist, and its 13 major symptom categories were subjected to exploratory
      principal components analysis. The resulting factors were correlated with
      relevant clinical variables. RESULTS: Principal components analysis identified
      four symptom dimensions explaining 55% of the total variance and broadly
      corresponding to those seen in adult samples. Boys were more likely to have
      sexual obsessions (34% vs. 18%, p = .01), whereas girls were more likely to
      endorse hoarding compulsions (53% vs. 36%, p=.009). High scores on the hoarding
      dimension were associated with increased levels of pervasive slowness,
      responsibility, indecisiveness, pathological doubt, depression and a variety of
      emotional difficulties, both self-rated and parent-rated. CONCLUSIONS: The
      structure of OCD symptoms is similar across the lifespan. Hoarding symptoms are
      prevalent in pediatric OCD, especially among girls, and are associated with
      greater levels of disability.

PMID- 18344901
TI  - Inadequate humoral immunogenicity to recombinant hepatitis B virus vaccine in
      biliary atresia children.
AB  - This study aimed to investigate the primary immunogenicity and the long-term
      efficacy of recombinant hepatitis B virus (HBV) vaccine in biliary atresia (BA)
      children. Fifty BA infants (age, 11 +/- 3.9 mo), and 23 BA patients at childhood
      (age, 8.5 +/- 0.22 y) were included for the evaluation of HBV surface antibody
      (anti-HBs) levels after three doses of recombinant HBV vaccine immunization. Age-
      and gender-matched healthy infants (n = 50) and children (n = 23) were enrolled
      as the control group. Serum samples of the study populations were collected for
      HBV seromarkers determination. In the absence of hepatitis B virus core antibody
      and HBV surface antigen, serum anti-HBs level above 10 IU/L was considered
      adequate immunogenicity to HBV vaccine. The prevalence of adequate anti-HBs
      levels after recombinant HBV vaccine in BA infants was significantly lower than
      those of the controls (p = 0.006). There was no difference in the prevalence
      between childhood BA patients and their matched controls (p = 0.538). In
      conclusion, adequate primary humoral immunity after the standard doses of
      recombinant HBV vaccine in BA infants is hard to establish. However, once
      immunity is acquired, BA children have adequate anti-HBs titer in the long run.

PMID- 18344902
TI  - Supplementation with galactooligosaccharides and inulin increases bacterial
      translocation in artificially reared newborn rats.
AB  - Supplementation of formulas with prebiotics enhances the growth of lactate
      producing bacteria, and fecal lactate, and acetate levels in infants. High
      concentrations of organic acids in intestinal lumen have, however, been shown to
      impair the intestinal barrier function. To determine whether stimulating the
      colonic microbiotal metabolism with prebiotics would impair the neonatal
      intestinal barrier function, artificially reared rats were fed milk formula with
      or without a mixture of galactooligosaccharides/inulin (GOS/Inulin, 88/12; 5.6
      g/L) from the 7th d of life (d7) until weaning (d20). At d18, GOS/inulin
      supplementation had increased the concentrations of acetate and lactate in
      colonic lumen. Although neither ileum-associated microbiota nor colonic
      permeability (assessed in Ussing chambers), nor the expression of tight junction
      claudin-2 and claudin-3 mRNA were altered, GOS/inulin supplementation was
      associated with increased bacterial translocation (BT) toward spleen. None of
      these effects persisted at d40. We conclude that GOS/inulin supplementation may
      increase BT in an immature gut. The balance between the potential infectious risk
      of BT vs. its putative beneficial effect on the maturation of neonatal immune
      system clearly warrants further study.

PMID- 18344903
TI  - Effects of brief, clustered versus dispersed hypoxic episodes on systemic and
      ocular growth factors in a rat model of oxygen-induced retinopathy.
AB  - Oxygen fluctuation patterns in preterm infants who develop retinopathy of
      prematurity (ROP) are varied and poorly represented in animal models. We examined
      the hypothesis that clustered (CL) episodes of hypoxia during hyperoxia results
      in a more severe form of oxygen-induced retinopathy (OIR) than dispersed
      episodes. Rat pups were exposed to alternating cycles of 1) 50% O2 with three CL
      episodes of 12% O2 every 6 h; or 2) 50% O2 with one episode of 12% O2 every 2 h,
      for 7 (P7) or 14 (P14) days postnatal age. Pups were killed after hyperoxia, or
      placed in room air (RA) until P21. RA littermates were killed at P7, P14, and
      P21. Systemic and ocular vascular endothelial growth factor (VEGF), soluble VEGFR
      1 (sVEGFR-1), insulin-like growth factor I (IGF-I), and growth hormone were
      examined. All hyperoxia-exposed retinas had evidence of neovascularization.
      Animals in the CL group had a more severe form of OIR at P21 evidenced by
      vascular tufts, leaky vessels, retinal hemorrhage, and vascular overgrowth. These
      characteristics were associated with low body weight; high systemic and ocular
      VEGF; and low systemic and high ocular sVEGFR-1 and IGF-I. These data suggest
      that preterm infants who experience CL fluctuations in Pao2 during supplemental
      O2 therapy are at a higher risk for severe ROP.

PMID- 18344904
TI  - Chronic hypoxia and rat lung development: analysis by morphometry and directed
      microarray.
AB  - It is unclear how sublethal hypoxia affects lung development. To investigate the
      effects of chronic hypoxia on postnatal lung remodeling, we treated neonatal rats
      with FIO2 of 0.12 for 10 d and analyzed lung development by morphometry and gene
      expression by DNA microarray. Our results showed the neonatal rats exposed to
      hypoxia reduced body weight by 42% and wet lung weight by 32% compared with the
      neonatal rats exposed to normoxia. In the neonatal rats exposed to hypoxia, the
      radial alveolar counts were decreased to 5.6 from 7.9 and the mean linear
      intercepts were increased to 56.5 mum from 38.2 mum. In DNA microarray analysis,
      approximately half of probed genes were unknown. Chronic hypoxia significantly
      regulated expression of genes that are involved in pathogenesis of pulmonary
      hypertension and postnatal lung remodeling. Chemokine ligand 12, jagged 2 were
      among those upregulated; c-kit, ephrin A1, and Hif-2alpha were among those
      downregulated. The altered expression of those genes was correlated with the lung
      development and remodeling.

PMID- 18344905
TI  - Negative tracheal pressure during neonatal endotracheal suction.
AB  - Endotracheal tube (ETT) suction is the most frequently performed invasive
      procedure in ventilated newborn infants and is associated with adverse effects
      related to negative tracheal pressure. We aimed to measure suction catheter gas
      flow and intratracheal pressure during ETT suction of a test lung and develop a
      mathematical model to predict tracheal pressure from catheter and ETT dimensions
      and applied pressure. Tracheal pressure and catheter flow were recorded during
      suction of ETT sizes 2.5-4.0 mm connected to a test lung with catheters 5-8
      French Gauge and applied pressures of 80-200 mm Hg. The fraction of applied
      pressure transmitted to the trachea was calculated for each combination, and data
      fitted to three nonlinear models for analysis. Tracheal pressure was directly
      proportional to applied pressure (r = 0.82-0.99), and catheter flow fitted a
      turbulent flow model (R = 0.85-0.96). With each ETT, increasing catheter size
      resulted in greater catheter flow (p < 0.0001) and thus lower intratracheal
      pressure (p < 0.0001). The fraction of applied pressure transmitted to the
      trachea was accurately modeled using ETT and catheter dimensions (R = 0.98-0.99).
      Negative tracheal pressure during in vitro ETT suction is directly proportional
      to applied pressure. This relationship is determined by ETT and catheter
      dimensions.

PMID- 18344906
TI  - Prenatal programming of renal function: the estimated glomerular filtration rate
      is influenced by size at birth in apparently healthy children.
AB  - Prenatal growth is known to affect glomerular function in adult life. It is
      unknown, however, whether this association is also present in children. In a
      cross-sectional study, we examined whether birth weight (BW) is associated with
      serum creatinine (measured by an improved Jaffe method) and GFR (estimated by the
      Haycock-Schwartz formula; eGFR) in 73 apparently healthy school-age children (35
      boys and 38 girls; age 9.5 +/- 0.4 yr). All children were born after singleton
      term pregnancies (gestational age 39.6 +/- 0.2 wk) with normal BW (3.2 +/- 0.04
      kg). A significant decrease in serum creatinine and increase in the eGFR was
      evident by tertiles of BW-SD score (SDS) (p = 0.001 and p < 0.0001). eGFR was
      correlated with BW-SDS (r = 0.45; p < 0.0001), so that each unit increase in BW
      SDS was associated with an increase in eGFR of 10 (95% CI 5-14) ml/min per 1.73
      m. In summary, estimates of glomerular function are in apparently healthy school
      age children influenced by size at birth. These findings suggest early effects
      for the prenatal programming of renal function in humans.

PMID- 18344907
TI  - 2007 Awards for Meritorious Contributions to Neuropathology.

PMID- 18344908
TI  - 2007 Awards for Meritorious Contributions to Neuropathology.

PMID- 18344909
TI  - Central nervous system tumors with ependymal features: a broadened spectrum of
      primarily ependymal differentiation?
AB  - Ependymomas are well-characterized central nervous system (CNS) tumors that occur
      most often in children and young adults. Several other CNS tumor entities,
      including astroblastoma, chordoid glioma, papillary tumor of the pineal region,
      angiocentric glioma, and pilomyxoid astrocytoma, variably display histopathologic
      features of ependymal differentiation. The ependymal differentiation in some of
      these tumors is generally accepted, whereas in others, it is controversial. This
      article briefly reviews ependymal cell development and conventional ependymomas,
      the pathologic findings and clinical behavior of tumors with variable ependymal
      features, and the rationales for their inclusion with ependymomas or exclusion
      from a larger family of ependymal tumors. These issues are addressed in the
      context of early morphologic insights of Bailey and Cushing, Friede, and others;
      contemporary oncologic concepts; and recent relevant molecular and tumor stem
      cell studies.

PMID- 18344910
TI  - Loss of Perineuronal Net in ME7 Prion Disease.
AB  - Microglial activation and behavioral abnormalities occur before neuronal loss in
      experimental murine prion disease; the behavioral changes coincide with a
      reduction in synaptic plasticity. Because synaptic plasticity depends on an
      intact perineuronal net (PN), a specialized extracellular matrix that surrounds
      parvalbumin (PV)-positive GABAergic (gamma-aminobutyric acid [GABA]) inhibitory
      interneurons, we investigated the temporal relationships between microglial
      activation and loss of PN and PV-positive neurons in ME7 murine prion disease.
      Anesthetized C57Bl/6J mice received bilateral intracerebral microinjections of
      ME7-infected or normal brain homogenate into the dorsal hippocampus. Microglial
      activation, PrP accumulation, the number of PV-positive interneurons, and
      Wisteria floribunda agglutinin-positive neurons (i.e. those with an intact PN)
      were assessed in the ventral CA1 and subiculum at 4, 8, 12, 16, and 20 weeks
      postinjection. Hippocampal areas and total neuron numbers in the ventral CA1 and
      subiculum were also determined. Loss of PN coincided with early microglial
      activation and with a reduction in synaptic plasticity. No significant loss of PV
      positive interneurons was observed. Our findings suggest that the substrate of
      the earliest synaptic and behavioral abnormalities in murine prion disease may be
      inflammatory microglia-mediated degradation of the PN.

PMID- 18344911
TI  - Increased expression of endoplasmic reticulum stress-related signaling pathway
      molecules in multiple sclerosis lesions.
AB  - Activation of endoplasmic reticulum (ER) stress-related cell signals has been
      reported in several neurologic disorders and may contribute to neurodegeneration.
      Endoplasmic reticulum stress is also linked to ischemic injury. However,
      activation of an ER stress response has not been investigated in multiple
      sclerosis (MS) lesions. We detected increased expression of ER stress-associated
      C/EBP homologous protein, immunoglobulin heavy chain-binding protein, and X-box
      binding protein 1 in multiple cell types, including oligodendrocytes, astrocytes,
      T cells, and microglia in active MS lesions. Semiquantitative analysis of
      expression in active, chronic active, and chronic inactive lesions indicated that
      levels of immunoglobulin heavy chain-binding protein were significantly higher in
      acute lesions than in non-MS controls or MS normal-appearing white matter, and
      that ER stress-associated C/EBP homologous protein was upregulated to the
      greatest extent at the edges of chronic active lesions. Because demyelination may
      be triggered by a tissue response to ischemia-like conditions, changes in the
      hypoxia-related antigen D-110 were also investigated, and it was found that
      increased ER stress-associated C/EBP homologous protein expression can occur in
      either the presence or absence of D-110. A possible link between a perturbed ER
      and lesion development in MS suggests a signaling pathway that may represent a
      new therapeutic target in MS.

PMID- 18344912
TI  - Guiding adult Mammalian sensory axons during regeneration.
AB  - Misdirection of axons after nerve injury impairs successful regeneration of adult
      neurons. Investigations of axon guidance in development have provided an
      understanding of pathfinding, but their relevance to regenerating adult axons is
      unclear. We investigated adult mammalian axon guidance during regeneration after
      peripheral nerve injury and focused on the effects of the prototypic guidance
      molecule nerve growth factor (NGF). Adult rat sensory neurons from dorsal root
      ganglia that expressed the NGF receptor tropomyosin-related kinase A (trkA) were
      presented with a point source of NGF in vitro. Naive trkA neurons had no net
      turning response to NGF, but if they had been preconditioned by a peripheral
      nerve transection in vivo before culturing, their growth cones were attracted
      toward the NGF gradient. A laminin substrate was required for this behavior and
      an anti-trkA antibody interrupted turning. These data demonstrate that injured
      adult mammalian axons can be guided as they regenerate. Moreover, despite the
      downregulation of trkA mRNA and protein levels within the dorsal root ganglion
      after injury, sensory neurons retain and increase trkA protein at the injury site
      where the regenerating axons are found. This may enhance the axonal response to
      NGF and allow guidance along an NGF gradient created in vivo in the distal nerve
      stump.

PMID- 18344913
TI  - Hepatic nuclear factor kappa B regulates neutrophil recruitment to the injured
      brain.
AB  - Acute brain injury is associated with induction of hepatic chemokine expression,
      which is an essential element in the subsequent recruitment of leukocytes to the
      damaged brain. To further understand the significance of the hepatic inflammatory
      response, we focused on nuclear factor (NF)-kappa B, a pivotal regulator of
      inflammation. Nondestructive real-time whole-body imaging was undertaken in the
      3XNF-kappa B-luciferase mouse to monitor NF-kappa B activation. Acute brain
      injury induced by intracerebral injection of interleukin-1 provoked rapid
      activation of hepatic and CNS NF-kappa B, with only minimal changes in other
      organs. Elevated NF-kappa B in the brain was limited to the site of the lesion,
      whereas hepatic NF-kappa B was widespread. The function of NF-kappa B in this
      model was determined by monitoring leukocyte recruitment to the liver and brain
      of nf kappa b1 mice, which lack the anti-inflammatory p50:p50 NF-kappa B
      homodimer. Brain injury in the nf kappa b1 mice was associated with increased
      neutrophil recruitment to the liver and brain compared with wild-type mice,
      thereby confirming a regulatory role for the NF-kappa B system. To determine the
      role of hepatic NF-kappa B, it was selectively inhibited by intravenous
      adenoviral-mediated delivery of an I kappa B alpha super-repressor. This
      treatment significantly reduced the numbers of neutrophils recruited to the
      brain. In conclusion, acute brain injury is associated with rapid and robust
      activation of hepatic NF-kappa B, which is required for efficient mobilization of
      circulating leukocytes to the brain.

PMID- 18344914
TI  - Experimental reovirus-induced acute flaccid paralysis and spinal motor neuron
      cell death.
AB  - Acute flaccid paralysis (AFP) describes the loss of motor function in 1 or more
      limbs commonly associated with viral infection and destruction of motor neurons
      in the anterior horns of the spinal cord. Therapy is limited, and the development
      of effective treatments is hampered by a lack of experimental models. Reovirus
      infection of neonatal mice provides a model for the study of CNS viral infection
      pathogenesis. Injection of the Reovirus serot Type 3 strains Abney (T3A) or
      Dearing (T3D) into the hindlimb of 1-day-old mice resulted in the development of
      AFP in more than 90% of infected mice. Acute flaccid paralysis began in the
      ipsilateral hindlimb at 8 to 10 days postinfection and progressed to paraplegia
      24 hours later. Paralysis correlated with injury, neuron loss, and spread of
      viral antigen first to the ipsilateral and then to the contralateral anterior
      horns. As demonstrated by the activation of caspase 3 and its colocalization with
      viral antigen in the anterior horn and concomitant cleavage of poly-(adenosine
      diphosphate-ribose) polymerase, AFP was associated with apoptosis. Calpain
      activity and inducible nitric oxide synthase expression were both elevated in the
      spinal cords of paralyzed animals. This study represents the first detailed
      characterization of a novel and highly efficient experimental model of virus
      induced AFP that will facilitate evaluation of therapeutic strategies targeting
      virus-induced paralysis.

PMID- 18344915
TI  - Gliomas in neurofibromatosis type 1: a clinicopathologic study of 100 patients.
AB  - There are few pathologic studies of gliomas in patients with neurofibromatosis
      type 1. We analyzed clinical and pathologic features of gliomas from 100
      neurofibromatosis type 1 patients (57 men; 43 women). The median age at tumor
      diagnosis was 13 years (range, 4 months to 68 years). Most tumors were typical
      pilocytic astrocytoma (PA) (49%) or diffusely infiltrating astrocytoma (DA) (27%)
      that included World Health Organization Grades II (5%), III (15%), and IV (7%);
      others were designated as low-grade astrocytoma, subtype indeterminate (LGSI;
      17%). Two pilomyxoid astrocytomas, 1 desmoplastic infantile ganglioglioma and 1
      conventional ganglioglioma, were also identified. The tumors in 24 cases arose in
      the optic pathways and included PA (n = 14), LGSI (n = 4), DA (n = 4), pilomyxoid
      astrocytoma (n = 1), and ganglioglioma (n = 1). The prognoses of the PA and LGSI
      gliomas overall were generally favorable; there were no survival differences
      between PA and LGSI groups based on site, tumor size, mitotic activity, or MIB-1
      labeling index. In the combined PA and LGSI group, age younger than 10 years and
      gross total resection were associated with an increased overall survival rate (p
      = 0.047 and 0.002, respectively). Compared with the combined group (PA + LGSI),
      patients with DA at all sites had decreased overall and recurrence-free survival
      times (p < 0.001 and p = 0.003, respectively). This study emphasizes the wide
      histologic spectrum of gliomas that occur in patients with neurofibromatosis type
      1. Classic PA and LGSI are the most common, and most have favorable prognoses. By
      contrast, DAs are more aggressive, similar to those that arise sporadically.

PMID- 18344916
TI  - Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release
      in neuromuscular synapses.
AB  - The beta-amyloid (AB) peptide25-35 contains the functional domain of the AB
      precursor protein that is both required for neurotrophic effects in normal neural
      tissues and is involved in the neurotoxic effects in Alzheimer disease. We
      demonstrated the presence of the amyloid precursor protein/AB peptide in
      intramuscular axons, presynaptic motor nerve terminals, terminal and myelinating
      Schwann cells, and the postsynaptic and subsarcolemmal region in the Levator
      auris longus muscle of adult rats by immunocytochemistry. Using intracellular
      recording, we investigated possible short-term functional effects of the AB
      fragment (0.1-10 micromol/L) on acetylcholine release in adult and newborn motor
      end plates. We found no change in evoked, spontaneous transmitter release or
      resting membrane potential of the muscle cells. A previous block of the
      presynaptic muscarinic receptor subtypes and a previous block or stimulation of
      protein kinase C revealed no masked effect of the peptide on the regulation of
      transmitter release. The aggregated form of AB peptide25-35, however, interfered
      acutely with acetylcholine release (quantal content reduction) when synaptic
      activity was maintained by electric stimulation. The possible relevance of this
      inhibition of neurotransmission by AB peptide25-35 to the pathogenesis of
      Alzheimer remains to be determined.

PMID- 18344917
TI  - [Atherosclerosis inflammation and rheumatic diseases].

PMID- 18344918
TI  - Management of cardiovascular risk factors in patients with systemic lupus
      erythematosus.

PMID- 18344919
TI  - Tregs and rheumatoid arthritis.
AB  - Regulatory T cells (Tregs) are a subset of T cells which are involved in
      peripheral immune tolerance. Their role in autoimmune disease which occurs
      through a breakdown of tolerance is of particular interest in trying to ascertain
      the mechanism(s) of disease progression. It is hoped that by understanding the
      role of Tregs in autoimmunity a reliable therapy may be developed to aid in both
      the treatment and potentially cure of disease. This review will focus on the
      naturally-occurring CD4+ CD25+ regulatory T cell subset and their possible
      involvement in rheumatoid arthritis.

PMID- 18344920
TI  - Dendritic cell subsets: their roles in rheumatoid arthritis.
AB  - Dendritic cells (DC) are now known to influence many different classes of
      lymphocytes (T, B, NK cells) and many types of T cell responses (Th1/Th2/Th17,
      regulatory T cells, peripheral T cell deletion). In rheumatoid arthritis (RA) DC
      have been described and their roles in RA pathogenesis have been implicated. This
      review summarizes the data obtained so far concerning the functional
      characterization of several DC subsets in human RA. Moreover, the effect of TNF
      alpha blockade on DC phenotype and function is also discussed. As most of the
      studies on DC in experimental arthritis have been conducted using
      (immunomodulated/tolerogenic) DC as tools to ameliorate experimental arthritis,
      we give some examples of how these cells may induce tolerance in vivo. Although a
      lot of work has been performed so far, the specific and functional roles of DC
      subsets in human RA and in CIA remain to be established. Achieving a detailed
      understanding of specific DC functions in RA holds potential for modulating DC
      for immunotherapy by down-regulating the autoimmune response.

PMID- 18344921
TI  - Multiple factors determine the increased prevalence of atherosclerosis in
      rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic inflammatory disease that presents not
      only involvement of joints but also endothelial dysfunction, dyslipidemia, and
      premature atherosclerosis. The death rate in RA is known to be higher than in the
      general population and clinical cardiovascular events secondary to
      atherosclerosis are responsible for the excessive death rate. A better
      understanding of the mechanisms that take part in the pathogenesis of
      atherosclerosis in RA patients is needed. Thus, the authors review the role of
      several factors involved in RA atherosclerosis, including disease activity, new
      cardiovascular risk factors, dyslipidemia and the association of atherosclerosis
      with the use of anti-rheumatic drugs, glucocorticoids and anti-tumor necrosis
      factor (TNF) agents. The role of humoral autoimmunity, namely autoantibodies
      against heat shock proteins, cardiolipin and beta2-glycoprotein I, and its link
      with atherosclerosis is also discussed. It is likely that the elucidation of the
      key mechanisms of atherogenesis in RA may determine a positive impact by reducing
      cardiovascular morbidity and mortality of these patients.

PMID- 18344922
TI  - [Hyperhomocysteinemia in children and adolescents with systemic lupus
      erythematosus: evolutive evaluation].
AB  - INTRODUCTION: One of the mechanisms implicated in the pathogenesis of coronary
      heart disease in patients with juvenile systemic lupus erythematosus (SLE) is the
      hyperhomocysteinemia. Our aim was to follow patients with juvenile SLE and to
      identify the presence and the persistence of hyperhomocysteinemia. METHODS: We
      studied 18 patients with juvenile SLE (median age 13.5 y). A survey of
      demographic and clinic data was performed based on patients records. The plasma
      homocysteine concentration was performed twice with a median interval of 1.5
      years (1.3-2.5) and association with nutritional status, disease activity, renal
      involvement and use of methotrexate was sought. The plasma homocysteine
      concentration was also evaluated in 59 healthy controls, sex and age-matched to
      the patients. RESULTS: Of the 18 patients with juvenile SLE, 16 (88.9%) were
      female and 13 (72.2%) had renal involvement. Five out of 18 patients (27.8%)
      persisted with increased concentration of plasma homocysteine (above the 90th
      percentile of the healthy group). The elevated concentration of homocysteine did
      not show statistically significant association neither with renal involvement (in
      the first dosage, p=0.676 and in the second, p=0.500), disease activity (in the
      first dosage, p=0.630 and in the second, p=0.182), overweight/obesity (in the
      first dosage, p=0.485 and in the second, p=0.288) nor with short stature (in the
      first dosage, p=0.202 and in the second, p=0.500). CONCLUSION: This study
      emphasizes the persistence of elevated concentration of homocysteine in some
      patients with juvenile SLE and the need for evaluations of therapeutic strategies
      and nutritional education aiming to reduce risk factors of cardiovascular
      disease.

PMID- 18344923
TI  - Clinical features of juvenile lupus erythematosus in Iranian children.
AB  - OBJECTIVE: Analysis of the clinical and laboratory features of childhood onset
      systemic lupus erythematosus (JSLE). PATIENTS AND METHOD: Forty five children,
      aged below 16, were enrolled in this retrospective multicenter study. All
      patients fulfilled the American College of Rheumatology revised criteria 1982 for
      the diagnosis of SLE and had shown clinical manifestations of the disease before
      the age of 16. RESULTS: The female to male ratio was 8:1. The mean age at onset
      was 10.5 (ranged between 3 and 16 years). Thirty patients (66%) were correctly
      diagnosed before referring to our Center. The clinical manifestation in different
      organs were as follows: 40 patients (88.8%) had skin involvement, 35 patients
      (77.7%) experienced musculoskeletal involvement, 29 children (64.4%) suffered
      from renal disease, hematological abnormalities were detected in 25 patients
      (55.5%), 12 patients (26%) had cardiovascular disease, 10 patients (17%)
      presented central nervous system involvement, and 5 patients (11%) experienced
      SLE-related pulmonary disease. During the follow up period, four patients died,
      two from renal failure, one from CNS complications of JSLE, and one due to severe
      sepsis. CONCLUSION: Clinical manifestations of Juvenile SLE are diverse and often
      severe. Similar studies should be undertaken in different geographic areas in
      order to provide a good insight of the disease towards a correct diagnosis of
      JSLE.

PMID- 18344924
TI  - [Cyclophosphamide induced amenorrhoea in pre-menopausal women with systemic lupus
      erythematosus].
AB  - OBJECTIVES: To determine the frequency of ovarian failure in pre-menopausal women
      after cyclophosphamide (cyc) treatment for systemic lupus erythematosus (SLE);
      identify risk factors for this complication; estimate the occurrence and
      viability of pregnancy during and after treatment. METHODS: Review of the data of
      women treated with intravenous cyc in the department of Rheumatology of Hospitais
      da Universidade de Coimbra, updated by interview. Information on demographic
      features; gynaecologic and obstetrical history; characteristics of the disease;
      duration and side effects of treatment were obtained. Ovarian failure was defined
      as a lack of menses for, at least, four months and the diagnosis was confirmed by
      hormonal measurements. RESULTS: Nineteen pre-menopausal women were treated with
      intravenous cyc in our department. The mean age at the time of cyc initiation was
      28.4 years. Lupus nephritis was the most common indication for cyc treatment
      (89.5%). The mean number of pulses was 9.3 over a period of 16.8 months. The mean
      cumulative dosage was 6.973 mg. Three patients developed ovarian failure. Those
      women were older than the others (P=0.0016). One patient became pregnant while on
      treatment. Two women delivered healthy children after cyc withdrawal. CONCLUSION:
      Ovarian failure developed in 15.8% of our patients. As described in the
      literature, the age at cyc initiation appears to be a determinant risk factor.
      Pregnancy may occur during cyc therapy, and thus, an effective contraception is
      mandatory. After cyc withdrawal, pregnancy is possible with a favourable outcome.

PMID- 18344925
TI  - Recommendations for the diagnosis and treatment of latent and active tuberculosis
      in inflammatory joint diseases candidates for therapy with tumor necrosis factor
      alpha inhibitors: March 2008 update.
AB  - The Portuguese Society of Rheumatology and the Portuguese Society of Pulmonology
      have updated the guidelines for the diagnosis and treatment of latent
      tuberculosis infection (LTBI) and active tuberculosis (ATB) in patients with
      inflammatory joint diseases (IJD) that are candidates to therapy with tumour
      necrosis factor alpha (TNFalpha) antagonists. In order to reduce the risk of
      tuberculosis (TB) reactivation and the incidence of new infections, TB screening
      is recommended to be done as soon as possible, ideally at the moment of IJD
      diagnosis, and patient assessment repeated before starting anti-TNFalpha therapy.
      Treatment for ATB and LTBI must be done under the care of a TB specialist. When
      TB treatment is indicated, it should be completed prior to starting anti-TNFalpha
      therapy. If the IJD activity justifies the need for immediate treatment, anti
      TNFalpha therapy can be started two months after antituberculous therapy has been
      initiated, in the case of ATB, and one month after in the case of LTBI. Chest X
      ray is mandatory for all patients. If Gohn s complex is present, the patient
      should be treated for LTBI; healed lesions require the exclusion of ATB. In cases
      of suspected active lesions ATB should be excluded/confirmed and adequate therapy
      initiated. Tuberculin skin test, with two units of RT23, should be performed in
      all patients. If the induration is <5 mm, the test should be repeated within 1 to
      2 weeks, on the opposite forearm, and will be considered negative only if the
      result is again <5 mm. Positive TST implicates LTBI treatment, unless previous
      proper treatment was provided. If TST is performed in immunossuppressed IJD
      patients, LTBI treatment should be offered to the patient before starting anti
      TNFalpha therapy, even in the presence of a negative test, after risk/benefit
      assessment.

PMID- 18344926
TI  - [Pulmonary and osteoarticular tuberculosis].
AB  - Tuberculosis is an important illness with an increasing prevalence in the last
      years in part due to AIDS. Considered primarily a pulmonary disease, tuberculosis
      can also affect almost any body system (nervous, genitourinary, and
      gastrointestinal as well as bones and joints) through lymphohematogenous spread.
      The authors present a case of pulmonary and osteoarticular tuberculosis diagnosed
      simultaneously.

PMID- 18344927
TI  - [Hemophagocytic Syndrome: a clinical presentation of systemic lupus
      erythematosus].
AB  - Hemophagocytic Syndrome is a clinical condition characterized by the activation
      of either macrophages or histiocytes with a prominent hemophagocytosis feature in
      the bone marrow and other reticuloendothelial systems. It leads to the
      phagocytosis of erythrocytes, leukocytes, platelets, and their precursors. The
      presence of hemophagocytosis can be associated to infections, malignancies,
      autoimmune diseases, drugs and a variety of other medical conditions. We report a
      case of a previously healthy 23 year-old woman that developed hemophagocytosis at
      the same time that she fulfilled diagnostic criteria for systemic lupus
      erythematosus. Lupus-related hemophagocytic syndrome is a rare and potentially
      fatal entity. It offers significant differential diagnosis challenges and
      requires urgent therapeutic intervention. There are only few cases reported in
      the literature. In this article, we briefly reviewed what is currently known
      about this syndrome. However, much is still needed in order to better understand
      its causes, all the immunopathogenic mechanisms, as well as its clinical aspects.

PMID- 18344928
TI  - [Coexistence of primary hyperparathyroidism and multiple myeloma: association and
      rare manifestations].
AB  - Diseases such as multiple myeloma and primary hyperparathyroidism are
      occasionally found in the elderly. Although very rare, the coexistence of both in
      the same patient has been described in the literature. The coincidence of
      manifestations of both diseases, namely hypercalcemia and osteopenia, may
      difficult the diagnosis, turning it into a challenge. The authors report a case
      of a female patient in whom the investigation of hypercalcemia and
      musculoskeletal manifestations led to a simultaneous diagnosis of multiple
      myeloma and primary hyperparathyroidism. With this case, they also emphasise
      clinical and radiological manifestations of these diseases, nowadays rarely
      observed, and related to the long time clinical evolution.

PMID- 18344929
TI  - [Evanescent rash].

PMID- 18344930
TI  - Drugs for migraine.

PMID- 18344931
TI  - Transforming growth factor-beta1 codon 10 polymorphism is associated with acute
      GVHD after allogenic BMT in Iranian population.
AB  - BACKGROUND: Certain cytokine genotypes are associated with acute graft versus
      host disease (aGVHD) after bone marrow transplantation (BMT). The present study
      aimed to determine existing association between TGF-beta1 codon 10 polymorphism
      and aGVHD after HLA-identical sibling BMT in the Iranian population.
      MATERIAL/METHODS: In a retrospective case-control study, 168 subjects including
      84 Iranian HLA-identical sibling BMT donor/recipient pairs were recruited. All of
      the patients were affected by hematological malignancies (AML=39, ALL=23 and
      CML=22). PCR-SSP method was performed to determine TGF-beta1 codon 10 T/C
      polymorphism genotypes. RESULTS: The frequency of TGF-beta1 codon 10 TT, TC and
      CC genotypes among all subjects were 26.8%, 33.3% and 39.9% respectively.
      Recipients with the T allele developed aGVHD significantly less than those
      without the T allele (odds ratio =0.334, P=0.026). CONCLUSIONS: Genetic
      background of TGF-beta1 may be involved as a protective factor in the development
      of aGVHD in HLA-matched sibling BMT in Iranian population. Moreover, this finding
      may indicate that the genetic markers in Iranians are, at least to some extent,
      linked to distinct genetic event from Japanese.

PMID- 18344932
TI  - Intentional conversion from tacrolimus to cyclosporine for HCV-positive patients
      on preemptive interferon therapy after living donor liver transplantation.
AB  - BACKGROUND: Recently we reported that signal transmission of interferon is more
      suppressed by tacrolimus (Tac) than cycrosporine (CyA). Therefore, although CyA
      might be beneficial immunosuppressive drug after liver transplantation (LT) on
      interferon therapy against hepatitis C virus, it is hesitated because of the risk
      for provocation of rejection. Herein initial outcome of our strategy, i.e.
      intentional conversion from Tac to CyA during preemptive interferon therapy after
      living donor LT (LDLT) was reported. MATERIAL/METHODS: Of 62 patients who had
      undergone LDLT in Nagasaki University Hospital between 1997 and November 2006, 16
      patients showed indications for hepatitis C-related liver cirrhosis. The median
      follow-up period was 15 months. Tac was used for all patients as induction
      therapy combined with steroids tapering. RESULTS: In 11 out of 16 cases (68.8%),
      preemptive Pegylated (Peg)-IFN-alpha 2b+Ribavirin therapy was initiated. When Peg
      IFN-alpha 2b+Ribavirin therapy was commenced, Tac-to- CyA conversion was done.
      The median period of conversion from Tac to CyA was 1.5 month after LDLT. After
      the conversion, ACR occurred in one case. Out of 11 patients, 3 patients (21.4%)
      showed early viral response (VR) at 3 months, 2 showed end-treatment response at
      48 weeks (14.3%) and 3 showed sustained VR (21.4%). CONCLUSIONS: Intentional
      conversion from Tac to CyA can be safely performed without increasing the risk of
      ACR.

PMID- 18344933
TI  - Associations of Human Leukocyte Antigen (HLA) haplotypes with risk of developing
      lymphoproliferative disorders after renal transplantation.
AB  - BACKGROUND: Genetic susceptibility to lymphomas associated with human leukocyte
      antigens (HLA) has been broadly reported for many years. In this study, we aimed
      to evaluate the potential impact of various HLA antigens on the incidence of
      lymphoproliferative disorders in renal allograft recipients. MATERIAL/METHODS: In
      this retrospective cross-sectional study, we analysed data of PTLD patients from
      two of the major Iranian transplant centers and compared them with 1155 normal
      kidney recipients. Potential impact of previously reported relevant HLA antigens
      was assessed. For assessing independent impact of various factors, we used a
      multivariate proportional hazard analysis using Cox regression. RESULTS: Patients
      in the two groups were similar in their age at transplantation. PTLD group was
      significantly female predominated (61% vs. 33%). chi(2) showed a higher frequency
      of HLA-BW22 in the PTLD group. HLA-A2, HLA-A11, HLA-B5 and HLA-B35 concomitant
      with azathioprine based immunosuppression were significantly associated with PTLD
      occurrence. CONCLUSIONS: Our findings can further alert us toward the initial
      signs of PTLDs in high risk kidney allograft recipients. Future prospective
      studies with larger patient population seem necessary for confirming our
      findings.

PMID- 18344934
TI  - Early hyperglycemia after allogenic kidney transplantation: does it induce
      infections.
AB  - BACKGROUND: Although impact of diabetes mellitus after solid organ
      transplantation is a broadly investigated issue, a potential impact of early
      hyperglycemia after renal transplantation has not received enough consideration.
      In this study, we aimed to evaluate the potential impact of early hyperglycemia
      on the hazards of infections development leading to re-hospitalization.
      MATERIAL/METHODS: We evaluated 1931 non diabetic renal allograft recipients,
      undergone renal transplantation at the Baqiyatallah Hospital, Tehran from 1984 to
      2006. Level of hyperglycemia was defined at 126 mg/dL. Patients who had at least
      two glucose concentration results over the mentioned level in two different days
      during their early post transplantation period were determined as hyperglycemic.
      RESULTS: Overall, 7.6% of patients were determined as having early post
      transplant hyperglycemia. Multivariable hazard analysis using Cox regression
      model showed that early post transplantation hyperglycemia has an independent
      impact on rehospitalization of non-diabetic kidney allograft recipients for
      developing infectious diseases. CONCLUSIONS: Regarding findings of our study and
      previous studies we conclude that renal transplant recipients who develop
      hyperglycemia during their early post transplantation period should receive
      higher amount of attention over their follow up periods.

PMID- 18344935
TI  - Post-transplant femoral head avascular necrosis: a selective investigation with
      MRI.
AB  - BACKGROUND: We investigated the presence of femoral head avascular osteonecrosis
      (FHAVN) by a selective investigation with MRI at follow-up. MATERIAL/METHODS: A
      total of 331(200 men, 131 women) renal transplants were included. They were
      transplanted at the mean age of 31.4 (9-63) years. The mean follow-up time of all
      patients after transplantation was 60.6 (6-233) months, and the mean current age
      36.6 (11-66) years. All transplants filled out a questionnaire on musculoskeletal
      symptoms and underwent a detailed clinical examination. Magnetic resonance
      imaging was done in cases of hip joint pain in groin, buttock, thigh and knee and
      in 50 asymptomatic transplants. FHAVN were identified according to Ficat Arlet
      classification. RESULTS: 43(13%) patients reported pain without previous trauma.
      In the clinical examination, limited ranges of motion of the hip were noted in 13
      of them. FHAVN was detected in 11 of 43 patients. Disease was bilateral in two of
      the eleven patients. Of the 662 femoral heads, 43 were associated with hip pain
      whereas the remaining 619 were asymptomatic. Avascular osteonecrosis was not
      confirmed in the asymptomatic 100 hips with magnetic resonance imaging.
      CONCLUSIONS: A selective investigation of FHAVN may be used to diagnose in renal
      allograft recipients with painful hips at follow-up. With a retrospective
      selective analysis, the presence of FHAVN was low among renal transplantation
      recipients at the end of the study.

PMID- 18344936
TI  - Colchicine against ischemia-reperfusion injury in experimental lung
      transplantation.
AB  - BACKGROUND: To asses the influence of colchicine, a potent antinflammatory agent
      and neutrophile migration inhibitor, on Ischemia-Reperfusion Injury (IRI) in rat
      lung isogeneic transplantation. MATERIAL/METHODS: Isogeneic, orthotropic single
      left lung transplantations were performed among male Wistar rats after total
      ischemic graft storage time of 12 or 18 hours in temperature of 4 degrees C.
      Recipients received either no specific treatment (control) or Colchicine 1.2
      mg/kg/d ip. Twenty-four hours after transplantation, the native contralateral
      lung was occluded to assess graft gas exchange function (PaO(2)). The lung graft
      was excised and assessed for Wet/Dry ratio (W/D) as a measure of edema,
      Myeloperoxidase activity (MPO) as a measure of neutrophile migration and
      histology. RESULTS: PaO(2) differences were not significant among all groups.
      Comparing colchicine to control group, the W/D ratio 3.93+/-0.66 vs. 1.86+/-0.32,
      p=0.002 and MPO 8.1+/-3.34 vs. 5.87+/-1.76, p=0.046 were significantly higher for
      18 hours colchicine group. Comparing 18 to 12 hours time groups, the W/D ratio
      5.70+/-1.53 vs. 1.86+/-0.32, p=0.007 for control groups and 5.40+/-1.49 vs.
      3.93+/-0.66, p=0.049 for colchicine groups were significantly higher for both 12
      h groups. Histology favored colchicine treated animals. CONCLUSIONS: Colchicine
      in tested dose does not decrease edema after lung transplantation and does not
      improve lung function. 18 vs. 12 hours total ischemic graft storage time causes
      less lung edema.

PMID- 18344937
TI  - The influence of donor-related factors on the frequency of acute cellular
      rejection by the recipient in the first year following heart transplantation.
AB  - BACKGROUND: This study was an attempt to identify donor-related factors
      influencing the frequency of acute cellular rejection episodes in cardiac
      transplant recipients in the first year following transplantation.
      MATERIAL/METHODS: The study encompassed 76 patients (14 women and 62 men) aged 6
      68 years, mean 47.8+/-16.3, who received a cardiac transplant at the Institute of
      Cardiology in Warsaw between 2001-2005. The period of observation was from day 7
      after transplantation (the day of the first biopsy by protocol) to the end of the
      first year. Follow-up at the outpatient department included physical examination,
      echocardiography, blood biochemistry and determination of circulating levels of
      immunosuppressive drugs. Endomyocardial biopsies were obtained and evaluated
      according to ISHLT criteria. The study was conducted according to the following
      biopsy schedule: every 7 days in the first month, every 14 days in the second,
      and every three months from month three to the end of the first year. The
      frequency of acute cellular rejection was assessed along with potential donor
      related factors (age, gender, donor cause of death). The study protocol was
      approved by the Local Bioethics Committee of the Institute of Cardiology.
      Comparative statistical analysis was conducted retrospectively using the Mann
      Whitney and Kruskal-Wallis tests. RESULTS: A total of 39 abnormal biopsies were
      found (degree 2 and 3 ISHLT) among the 750 biopsies performed (5.2%). No
      significant differences were found in the number of acute cellular rejection
      episodes in relation to treatment protocol and blood cyclosporine concentration
      in the studied period. Acute cellular rejection was occured significantly more
      frequently when intracerebral hemorrhage was the donor's cause of death
      (p<0.0131) and showed a tendency to occur more frequently when the donor was
      female (p<0.0611). The effects of donor age, blood type and duration of ischemia
      were not significant. CONCLUSIONS: Significantly more episodes of acute cellular
      rejection occur in recipients of hearts from donors who died from intracerebral
      hemorrhage. A trend towards more frequent episodes of acute cellular rejection
      appears when the donor was female.

PMID- 18344938
TI  - Renal transplantation practice in Iran and the Middle East: report from Iran and
      a review of the literature.
AB  - Transplantation is the best treatment of end-stage renal disease (ESRD. Life
      expectancy, the quality of life and reduced medical expenses are greater with
      kidney transplantation than with maintenance dialysis. However, organ shortage
      remains the central problem in kidney transplantation. To tackle this problem,
      we, in Iran, have initiated a living unrelated donor (LURD) program using
      emotionally related persons, friends and well-motivated volunteers as organ
      donors, which resulted in eliminating the waiting list. The Iranian transplant
      program is the most active in the Middle East region in providing equitable,
      quick, and intermediary-free access to affordable kidney transplantation for
      everyone regardless of gender and economic circumstances. The results of
      transplants from living unrelated donors have been very encouraging. This article
      deals with the kidney transplantation practice in Iran and other Middle Eastern
      countries, and describes Iran's kidney transplantation experience with cadaveric,
      living related and living unrelated donors. In conclusion, kidney transplantation
      experience in the Middle East region is an active practice. Most countries have
      uplifting trends and effective programs are establishing inside countries.
      However, the practice should be further promoted and organized towards allograft
      procurement from deceased donors and in this way passing and enacting proper
      legislations must be more seriously taken into consideration.

PMID- 18344939
TI  - The role of IL-6 during the late phase of liver regeneration.
AB  - BACKGROUND: The storage of organs for liver transplantation has resulted in
      expanding the donor pool for the "living-related" organ donors. Hence,
      understanding the factors that moderate liver regeneration, both in donor and
      recipient, is of great importance. Liver regeneration is accompanied by an
      appearance of cytokines, growth factors and hormones which enable hepatocytes
      acquiring the ability to reenter the cell cycle. Within few hours after partial
      hepatectomy (PH) increase concentration of a large number of mitogens for
      hepatocytes. Among them essential function in recovering after PH plays
      interleukin 6 (IL-6). However the gene expression of this factor after the
      reconstruction of the liver is completed is still uncertain. We have assessed the
      gene expression of IL-6 during liver regeneration in tissue of regenerating liver
      in tenth day after PH. MATERIAL/METHODS: Materials for the research were obtained
      from 12 rats. PH surgeries were performed on 7 rats (study group), on the 5 left
      laparotomy was performed (control group). In the tenth day after surgery on whole
      12 animals hepatectomy was performed. RNA was isolated from tissues and then
      copied to cDNA. Using real-time polymerase chain reaction (real-time PCR) the
      gene expression of IL-6 was defined. The Mann-Whitney-Wilcoxon Test was performed
      for the statistic analysis. The p<0,05 was considered as statistically
      significant. RESULTS: mRNA transcripts for IL-6 in study group compared to
      control group were 6-fold elevated 10 days following PH (p=0,03). CONCLUSIONS:
      These results indicate that IL-6 plays a pivotal role in liver regeneration.
      Elevated level of mRNA transcripts for IL-6 is sustained even after the operation
      and rebuild of the organ size.

PMID- 18344940
TI  - No transmission of porcine endogenous retroviruses (PERVs) in a long-term pig to
      rat xenotransplantation model and no infection of immunosuppressed rats.
AB  - BACKGROUND: Xenotransplantation from pig to humans may be associated with the
      risk of transmission of porcine endogenous retroviruses (PERVs) that are present
      in the genome of all pigs and that infect human cells in vitro. However, it
      remains unclear whether PERVs infect transplant recipients in vivo and, if so,
      whether they are pathogenic. It is therefore essential to perform in vivo
      infection studies in animal models. MATERIAL/METHODS: To study PERV transmission
      in rats, rat primary cells and cell lines were treated in vitro with virus from
      different sources. Based on the assumption that susceptible cell lineages not yet
      tested in vitro could be present in the animal, PERV was inoculated into naive
      and immunosuppressed animals. To investigate PERV transmission in a long-term
      exposure experiment, sera from animals grafted with pig Langerhans islet cells
      were tested in a Western blot assay for antibodies against PERVs. The animals
      were treated with streptozotocin to induce diabetes and microencapsulated and non
      microencapsulated pig islet cells were applied without immunosuppression.
      RESULTS: No productive infection of a few selected rat primary cells or cell
      lines was observed in vitro. PERV-specific antibodies were found in none of the
      animals and no integration of PERV into rat cells of different organs was
      observed, indicating that infection had not occurred. CONCLUSIONS: This report
      demonstrates a lack of infection of rats in vivo even during immunosuppression or
      long-term exposure (up to 460 days) to a functioning xenotransplant. This report
      also shows that rats possibly due to a low receptor concentration on their cells
      are not a suitable animal model to study PERV transmission in vivo.

PMID- 18344941
TI  - Safety and efficacy of high dose ATG bolus administration on rewascularization in
      kidney graft patients--long term results.
AB  - BACKGROUND: Various preparations of ALG/ATG have been used in clinical
      transplantation for more than 30 years. In recent years the number of high
      immunological risk patients has increased and biological agents are being used as
      induction therapy. The aim of this prospective, randomized study was to asses the
      safety and efficacy of a single high dose of antithymocyte globulin (9 mg/kg ATG
      Fresenius S) in cadaveric renal transplantation. The maintenance
      immunosuppressive regimen consisted of steroids, mycophenolate mofetil (converted
      after the fourth month to azathioprine), and cyclosporine. MATERIAL/METHODS:
      Between November 1997 and April 1999, 79 recipients were included into the study.
      Patients were randomized to ATG (n=40) or the standard treatment group (n=39)
      with a follow up period of 5 years. RESULTS: The incidence of acute rejection was
      lower in the ATG group--9 patients (22.5%) compared to 14 in the control group
      (35.9%) (p=NS). The total number of all acute rejections episodes in the ATG
      group was 11 and 23 in the control group. Steroid resistant rejections occurred
      in 4 (10%) and 8 (20.5%) patients respectively. The number of infectious
      complications was similar in both groups (65% - ATG, 67.5% - control, p=NS).
      Graft survival was 70% for the ATG and 69.23% for the control group. Death
      censored graft survival was 85% in the ATG and 74.43% in the control group
      (p=NS). CONCLUSIONS: Induction Therapy with high single dose of ATG seems to be
      safe and efficacious in kidney transplantation.

PMID- 18344942
TI  - An attempt to assess the influence of primary disease on the results of
      therapeutic rehabilitation in an early post-operative period in orthotopic liver
      transplant recipients.
AB  - BACKGROUND: A retrospective analysis of the effects of early postoperative
      rehabilitation in patients undergoing orthotropic liver transplantation in
      correlation to the primary liver disease leading to transplantation. MATERIALS
      AND METHODS: In between 2000 and 2003 in the Department of General, Transplant
      and Liver Surgery of the Medical University of Warsaw Central Teaching Hospital,
      213 orthotropic liver transplants (OLT) were performed. Full rehabilitation
      records were available for 136 patients. For statistical analysis, patients were
      divided into 5 different groups representing different causes of primary liver
      insufficiency. RESULTS: Achieved early rehabilitation results show that there was
      a strong correlation between the time at which physiotherapy was introduced and
      the ability to achieve a fully upright position in correlation to the primary
      cause of liver disease necessitating transplantation. The shown relationship is
      probably a direct effect of the time of disease progression before
      transplantation is required. The worst results were observed in group no. 4 where
      patients with acute and subacute liver insufficiencies were included, even though
      these patients had the lowest mean age. CONCLUSIONS: 1. The achieved results
      confirm the general compensation rule which states that the process of healing
      strongly depends on the time of disease development. 2. An analysis of the time,
      when rehabilitation was initiated and the ability of the patient to achieve a
      fully upright position in relation to the cause of liver insufficiency suggests
      that the reason for most delays is the inability to develop adequate
      compensational mechanisms as a result of rapid disease progression in cases of
      acute liver insufficiency.

PMID- 18344943
TI  - BCNU toxicity presenting with a large pericardial and pleural effusion.
AB  - BACKGROUND: Carmustine (BCNU), 1, 3-bis (2-chloroethyl)-1-nitosourea, is an
      alkylating agent which is commonly used as a part of conditioning regimen for
      autologous peripheral blood stem cell transplantation. Despite the widespread use
      of BCNU therapy in adults, cardiopulmonary toxicity presenting with cardiac
      tamponade has not been reported. CASE REPORT: We present a patient who received
      BCNU as part of her conditioning regimen followed by autologous peripheral blood
      stem cell transplantation. This patient subsequently developed bilateral upper
      lobe pulmonary infiltrates with bilateral pleural effusions and a large
      pericardial effusion which was a result of BCNU toxicity. CONCLUSIONS: Early
      institution of glucocorticoids for patients receiving high dose BCNU containing
      chemotherapeutic regimens has shown to significantly reduce BCNU induced cardio
      pulmonary toxicity.

PMID- 18344944
TI  - Anti-Fya antibodies as the cause of an unfortunate post-transplant course in
      renal transplant recipient.
AB  - BACKGROUND: Duffy glycoprotein, belonging to blood group alloantigens, is also
      recognized as chemokine-binding protein, therefore the role of Duffy antigen in
      chemokine distribution has been postulated. Duffy positive phenotype prevalent
      among Caucasians is associated with antigen expression on erythrocytes and
      endothelium of several organs including kidney. The role of anti-Duffy antibodies
      significant in transfusiology may be also important in kidney transplantation.
      CASE REPORT: The case of renal transplant recipient with Fy (a-b+) phenotype,
      possessing anti Fya antibodies, with unfortunate post-transplant course
      complicated with acute cellular and antibody-mediated graft rejections, with the
      presence of crescentic glomerular lesions, kidney graft insufficiency and
      recurrent urinary tract infections is presented. The role of anti-Duffy
      antibodies in acute antibody-mediated rejection is discussed. CONCLUSIONS: Fy(a
      )antibodies present in renal recipient with Fy(a-b+) phenotype may be the reason
      for unfavorable transplantation outcome resulting from reaction against Duffy
      antigen up-regulated on graft tissue during ischemia reperfusion injury and acute
      rejection episode. In renal transplant recipients with antibody-mediated
      rejection without antidonor specific antibodies, incompatibility in blood group
      antigens other than AB0 system could be considered.

PMID- 18344945
TI  - The influence of visible light exposure on cultured RGC-5 cells.
AB  - PURPOSE: To determine the effects of visible light on normal or metabolically
      compromised cultured rat RGC-5 cells. METHODS: Cultured RGC-5 cells were exposed
      to different durations as well as intensities of optical radiation, filtered to
      exclude wavelengths below 400 nm. Some cells were also subjected to metabolic
      compromise by depriving them of serum (serum deprivation; SD). Treated cells were
      assayed for cell viability using the 3,(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) reduction assay, for DNA breakdown by terminal
      deoxynucleotidyl transferase (TdT)-mediated d-UTP-linked nick end labeling
      (TUNEL), apoptotic protein activation by immunoblotting, and the production of
      reactive oxygen species (ROS) with dihydroethidium. A subset of cells was treated
      with 100 pM rotenone as an alternative means to induce metabolic stress; this was
      to determine that the influence of light on compromised cells was not specific to
      serum-deprivation alone. RESULTS: Exposure to the light for 48 h activated both
      caspase-3 and Bcl-associated X-protein (Bax) in cultured RGC-5 cells.
      Furthermore, light (1000 or 4000 lux), SD, and rotenone caused minor but
      significant decreases in cellular MTT reduction. SD and light also led to
      cellular DNA breakdown, although only light caused ROS production. Light (48 h)
      significantly exacerbated the effect of SD on MTT reduction and DNA cleavage.
      Furthermore, the antioxidant, trolox, significantly blunted the detrimental
      influence of light on cell viability, increase in TUNEL-positive cells, and the
      generation of ROS. CONCLUSIONS: Exposure to light was slightly, but
      significantly, harmful to healthy RGC-5 cells alone, but was much more toxic to
      those cells that were energetically compromised. Continuous light exposure can
      therefore detrimentally affect metabolically stressed RGC-5 cells. This may have
      implications for some ocular retinopathies such as glaucoma.

PMID- 18344946
TI  - Further ideas to speed up early surgical training.

PMID- 18344947
TI  - Trabeculectomy is not the best surgical option for glaucoma.

PMID- 18344950
TI  - Optic neuropathy associated with dengue fever.
AB  - PURPOSE: To report a case series of three patients of optic neuropathy associated
      with dengue fever. METHODS: Observational case series. RESULTS: Three patients
      aged of 19, 31, and 40 years (cases 1, 2, and 3) complained of unilateral
      blurring of vision within a week of being diagnosed with dengue fever. Their
      presenting visual acuities were counting fingers in cases 1 and 2, and 6/6 in
      case 3, with features suggestive of optic neuropathy. Two of the three patients
      (cases 2 and 3) had bilateral ocular signs. The visual acuity recovered to 6/9 in
      case 1, worsened to no light perception in case 2, and remained unchanged in case
      3. CONCLUSIONS: Although spontaneous visual recovery is possible, optic
      neuropathy associated with dengue fever may result in severe and permanent visual
      loss.

PMID- 18344951
TI  - Retinal nerve fiber layer thickness in patients with retinitis pigmentosa.
AB  - PURPOSE: To study retinal nerve fiber layer (RNFL) thickness in patients with
      retinitis pigmentosa (RP). DESIGN: Cross-sectional observational study. METHODS:
      One hundred and thirty-seven eyes of 137 patients with RP were examined. The
      effect of age, gender, laterality, inheritance trait, spherical equivalent
      refractive error, visual acuity, and the extent of visual field defect on RNFL
      thickness measured with optical coherence tomography were analyzed by a multiple
      linear regression model. RESULTS: The average RNFL thickness was 104.1+/-21.7
      microm. The multiple R(2) for the model was 0.349. Among the variables studied,
      ageing and being male were significant risk factors for thinner RNFL thickness.
      RNFL thickness was not correlated with inheritance trait, laterality, refractive
      error, visual acuity, or the extent of visual field defect. CONCLUSION: RNFL
      thickness in RP patients was not correlated with visual function but ageing as in
      the normal subjects. Currently proposed therapies, including photoreceptor
      rescue/transplantation and visual prosthesis, are based on the premise that the
      inner retinal structures are relatively retained despite the profound loss of
      photoreceptors. The present result supports this notion.

PMID- 18344952
TI  - Heavy tamponade 1: a review of indications, use, and complications.
AB  - BACKGROUND: Heavier than water intraocular tamponades have several theoretical
      advantages over conventional tamponades, especially in the treatment of
      complicated retinal detachments and proliferative viteroretinopathy of the lower
      fundus periphery. However, initial clinical series of various heavy tamponades
      have reported significant complication rates. Therefore, heavy tamponades have
      not found widespread acceptance. Three recently developed heavy silicone oil
      tamponades, Oxane HD, Densiron 68, and HWS 46-3000, are much better tolerated and
      presently seem to enter routine clinical practice. MATERIALS AND METHODS:
      Literature review of 21 publications on the clinical application of 9 different
      heavy tamponades (fluorosilicone, C10F18, F6H8, OL62HV, Oxane HD, O62, F6H8
      silicone oil mixture, Densiron 68, and HWS 46-3000). RESULTS: The first
      generation (fluorinated silicone and perfluorocarbon liquids) and second
      generation (partially fluorinated alkanes) of heavy tamponades were associated
      with relatively high complication rates, for example, tamponade emulsification,
      intraocular inflammation, and rise in intraocular pressure. The complication
      spectrum of the new generation of heavy silicone oils (Oxane HD, Densiron 68, and
      HWS 46-3000) seems to be comparable to conventional silicone oil tamponades while
      providing better support for the inferior retina and the posterior pole.
      CONCLUSION: The recently developed heavy silicone oil tamponades are safe and
      effective tools for the use of complicated retinal detachments of the inferior
      fundus.

PMID- 18344953
TI  - Anatomical and visual outcome after vitrectomy with triamcinolone acedonide
      assisted epiretinal membrane removal in highly myopic eyes with retinal
      detachment due to macular hole.
AB  - PURPOSE: To determine the effectiveness of staining an epiretinal membrane (ERM)
      with triamicinolone acedonide (TA) during vitrectomy for a retinal detachment
      (RD) due to a macular hole (MH) in highly myopic eyes. PATIENTS AND METHODS:
      Thirty-four highly myopic eyes (>-6.0 dioptres) of 34 patients with an RD caused
      by an MH underwent vitrectomy with TA-assisted ERM removal. The excised ERMs from
      five eyes were examined by transmission electron microscopy (TEM). The main
      outcome measures were the retinal status and best-corrected visual acuity (BCVA).
      The anatomic status of the MH was determined by optic coherence tomography (OCT)
      in 24 successfully retinal-reattached eyes. The follow-up periods ranged from 5
      to 20 months. RESULTS: The granules of TA adhered to the ERM and the residual
      posterior hyaloid, which made them more visible and facilitated their removal.
      Tissues resembling the internal limiting membrane were not detected in any of the
      five excised tissues. The retinal reattachment rate was 88% after the first
      surgery. The mean log MAR BCVA significantly improved from 1.83+/-0.50 (mean+/
      SD) before surgery to 1.22+/-0.35 at the final follow-up (P<0.001, Wilcoxon
      signed rank test). OCT showed a normal concave appearance in 11 of 24 eyes (46%),
      but a central neural epithelial defect was present in 13 of 24 eyes (54%).
      CONCLUSIONS: TA facilitates the complete removal of both the ERM and residual
      posterior hyaloid, thus ensuring high anatomical and visual success rates in
      highly myopic eyes with an RD due to MH.

PMID- 18344954
TI  - Discrete arcs of increased fundus autofluorescence in retinal dystrophies and
      functional correlate on microperimetry.
AB  - PURPOSE: To describe the occurrence of discrete arcs of increased fundus
      autofluorescence (FAF) associated with various retinal dystrophies and to assess
      their functional significance by fundus-controlled microperimetry. METHODS: Seven
      patients, three with pigmented paravenous retinochoroidal atrophy (PPRCA), one
      with sector retinitis pigmentosa (RP), one with typical RP, and two with macular
      dystrophy were assessed by retinal imaging including FAF imaging. Serial images
      were obtained within a review period of 6 and 10 years in a patient with PPRCA
      and macular dystrophy, respectively. Fundus-controlled microperimetry was
      performed in eight eyes of five patients to determine light increment
      sensitivity. RESULTS: A discrete arched line of increased FAF was observed
      without obvious correlate on fundus biomicroscopy. The orientation of this line
      differed from ring shape in RP and macular dystrophy, a semi-circle structure in
      sector RP to crescent shape with tiplike extensions towards branching retinal
      veins in PPRCA. Longitudinal investigation revealed slight migration of the arc
      in PPRCA and peripheral extension of the ring diameter in macular dystrophy.
      Microperimetry revealed that the arc of increased FAF sharply delineated areas of
      severely impaired retinal sensitivity. CONCLUSIONS: The findings indicate that
      arcs of increased FAF in PPRCA and other retinal dystrophies demarcate areas of
      impaired retinal function and may migrate over time. FAF imaging may therefore
      reveal the exact extent of neurosensory dysfunction that may exceed the
      dimensions anticipated by conventional examinations.

PMID- 18344955
TI  - Ocular Behcet's disease presenting with retinal tear and panuveitis.

PMID- 18344956
TI  - Intravitreal bevacizumab for treatment of chronic central serous
      chorioretinopathy.

PMID- 18344957
TI  - Psychological aspects of cytogenetic testing of uveal melanoma: preliminary
      findings and directions for future research.
AB  - PURPOSE: To determine the proportion of uveal melanoma patients who accept
      cytogenetic prognostication and to understand the reasons for their decision and
      the psychological impact of an adverse prognosis. METHODS: Patients treated by
      enucleation or local resection for uveal melanoma between 01 January 2003 and 31
      December 2006 were identified and the proportion undergoing cytogenetic studies
      was determined. In-depth interviews of fourteen patients living near our centre
      were conducted to determine their reasons for accepting cytogenetic testing and
      their reactions to any results received. RESULTS: In total 97% of 298 eligible
      patients with uveal melanoma treated by enucleation or local resection accepted
      an offer of cytogenetic prognostication. None of the patients interviewed in
      detail expressed any regret about having this test and there was no evidence of
      any harm. The main benefit perceived by patients was that they would have greater
      control and that screening for metastatic disease and early treatment might
      enhance chances of survival. This was despite counselling that prognostication,
      screening, and treatment are unlikely to prolong life and that the main purpose
      of cytogenetic studies is to allow for life-planning. CONCLUSIONS: Almost all
      patients with uveal melanoma desire cytogenetic prognostication, although not for
      the reasons intended by their medical practitioners. Further studies are needed
      to understand patients' reactions to cytogenetic testing, so that care can be
      optimised.

PMID- 18344958
TI  - Laser scanning in vivo confocal microscopy and quantitative aesthesiometry reveal
      decreased corneal innervation and sensation in keratoconus.
AB  - PURPOSE: The purpose of this study was to quantitatively analyse laser scanning
      in vivo confocal microscopy images of the corneal epithelium and sub-basal nerve
      plexus in patients with keratoconus and to correlate these microstructural
      observations with corneal sensitivity. METHODS: A total of 31 eyes of 31 normal
      human subjects, and 27 eyes of 27 subjects with an established diagnosis of
      keratoconus were recruited. Twelve subjects with keratoconus had never worn
      contact lenses (K-NCL). Fifteen subjects with keratoconus wore contact lenses
      routinely (K-CL). All eyes were examined using slit-lamp biomicroscopy, Orbscan
      topography, non-contact corneal aesthesiometry, and laser scanning in vivo
      confocal microscopy. RESULTS: Central corneal sensation was significantly lower
      in K-CL compared to normal (P=0.028). However, there was no significant
      difference in corneal sensation between the normal and K-NCL groups (P=0.059).
      Both sub-basal nerve density (P<0.001) and basal epithelial density (P<0.001)
      were significantly lower than normal in all keratoconic subjects. Central corneal
      sensation was only significantly correlated with sub-basal nerve density
      (P=0.001) and was not significantly correlated with any of the basal epithelial
      parameters. Sub-basal nerve density showed significant positive correlation with
      basal epithelial density (P<0.001). CONCLUSION: This quantitative study reveals
      decreased corneal innervation, sensation, and basal epithelial density in
      keratoconus. The results of this study provide strong evidence that both the sub
      basal nerves and the basal epithelium may be involved in the pathogenesis of
      keratoconus, although it is uncertain whether these are primary or secondary
      changes.

PMID- 18344959
TI  - Productivity of key informants for identifying blind children: evidence from a
      pilot study in Malawi.
AB  - OBJECTIVES: To determine the productivity of village-based 'key informants' (KIs)
      in identifying blind children. MATERIALS AND METHODS: Ngabu subdistrict
      (population 101,000) of Chikwawa district was divided into KI catchment areas.
      KIs, selected by local village leaders, were trained to register children
      reported to be blind or with severe visual impairment. These children were
      clinically assessed at designated centres. RESULTS: In total, 44 KIs were
      selected and trained to cover 196 villages in Ngabu. They identified and referred
      151 children, 37 of whom were blind (presenting vision <3/60 best eye). Overall,
      village leaders tended to choose female KIs (80%) compared to male KIs (20%);
      however, male KIs tended to be more productive, identifying 4.22 children each
      (compared to 3.23 for female KIs). Male KIs were 2.7 times more likely to
      identify blind children compared to female KIs. Only 25% of all identified blind
      children of school going age were in school. CONCLUSIONS: KIs may be effective in
      identifying blind children in the community; however, additional work is needed
      to determine who will be the most effective KI in a community and whether gender
      roles will limit interpretation of findings from KIs activities.

PMID- 18344960
TI  - Clinicopathologic correlation of a subconjunctival foreign body using ultrasound
      biomicroscopy and anterior segment ocular coherence tomography.

PMID- 18344961
TI  - Current clinical practice of consultant ophthalmologists in treating herpetic eye
      disease in the United Kingdom.

PMID- 18344962
TI  - Exploring glaucoma awareness and the utilization of primary eye care services:
      community perceived barriers among elderly African Caribbeans in Chapeltown,
      Leeds.

PMID- 18344963
TI  - Pathological changes in the vitreoretinal junction 1: epiretinal membrane
      formation.
AB  - PURPOSE/BACKGROUND: Epiretinal membrane (ERM) formation is a common change
      resulting in disturbance of macular vision and predisposing to rhegmatogenous
      retinal detachment. Current treatment strategies rely chiefly on surgical removal
      of the membranes from the surface of the retina, allowing the retina to remodel
      and reattach. Improved knowledge of the pathological process behind the formation
      of these membranes, particularly knowledge of the cell types involved in their
      formation, is likely to increase our understanding of the way this group of
      diseases behave and to improve treatment. METHODS: We reviewed the histological
      findings of 109 surgically removed specimens and correlated these to age-related
      changes seen in a 32 cadaver eyes studied after corneal harvesting. The samples
      were studied using light microscopy and immunocytochemistry. RESULTS: In all
      cases of idiopathic ERMs, including cellophane maculopathy, macular hole, and
      vitreomacular traction syndrome, laminocytes were the exclusive cell type
      present. In cases of macular pucker associated with retinal tears, the membranes
      contain variable cohesive groups of retinal pigment epithelial (RPE) cells in
      addition to laminocytes. In cases of proliferative diabetic retinopathy,
      membranes consist almost entirely of capillaries and hyaline stromal tissue, with
      or without haemosiderin pigment and RPE cells and in which laminocytes and ILM
      were not identified. In cadaver eyes PVD was seen in 17/32 (53%) of cases, and
      the vitreous was attached in 14/32 (43.7%) and in one case no vitreous was
      present. Isolated laminocytes were present on the retinal surface in 12/18 cases
      with detached vitreous and in 1/14 cases with attached vitreous. In all cases
      laminocytes were scanty and confined to the optic nerve head, macular or
      subjacent macular retina. Immunohistochemistry findings indicate that laminocytes
      are positive for glial fibrillary acidic protein (GFAP), cytokeratin marker
      AE1/AE3, type II collagen, and type IV collagen. In some cases novel basement
      membrane formation was seen. There was a tendency for increased positivity of
      GFAP and AE1/AE3 with increased cellularity, and where novel basement membrane
      formation was present. CONCLUSION: Laminocytes are the fundamental cell type in
      idiopathic ERMs. These cells are frequently found in small and dispersed numbers
      in eyes containing a PVD. The presence of retinal pigment cells invariable
      indicates proliferative retinopathy and is only seen in association with a
      retinal detachment or tear. Diabetic membranes are composed of neovascular
      stromal tissue, which is most likely to be a response to retinal hypoxia.

PMID- 18344964
TI  - Asteroid hyalosis: pathogenesis and prospects for prevention.
AB  - Asteroid hyalosis (AH) is a common degenerative process in which fatty calcium
      globules collect within the vitreous humour. The condition rarely causes visual
      disturbances, and surgical removal is only rarely required. The presence of AH
      has been associated with systemic diseases such as diabetes; however, research in
      this area has been hampered by the lack of an animal model of AH. Recently, we
      have reported that AH occurs in galactose-fed beagles that develop the advanced
      stages of diabetes-like retinopathy. Comparisons of vitreous humour containing
      asteroid bodies (ABs) collected from these galactose-fed beagles and vitreous
      samples from age-matched normal beagles without ABs indicate that ABs contain
      calcium and phosphorous. Subtraction analysis of chloroform extracts of the
      vitreous samples by electrospray mass spectroscopy resulted in the identification
      of the quasimolecular ion of 1,2-dipalmitoyl-glycero-3-phosphoethanolamine (DPPE)
      as the main component of ABs. Since several reports indicate that ABs are
      composed of lipid-calcium complexes, we have proposed that the main component of
      ABs in the galactose-fed dogs with AH is a quasimolecular ion of DPPE in which
      two molecules of DPPE are complexed through their phosphates groups with calcium.
      We suggest that these lipid components diffuse into the vitreous from the
      degenerating retinas of these dogs.

PMID- 18344965
TI  - The pathologist's perspective on vitreous opacities.
AB  - BACKGROUND: Vitreous opacities are diverse in nature. Many underlying diseases
      are sight-threatening and several are also lethal. This review presents the
      pathologist's perspective of vitreous opacities, correlates laboratory findings
      with the underlying disease and recommends safe methods for handling specimens.
      An aetiological classification of vitreous opacities is also proposed. METHODS: A
      gentle fixative such as Cytolyt or HOPE-fixation is required, unless delivery of
      the vitreous biopsy specimen to the laboratory can be guaranteed within two
      hours. Cells and other material are precipitated onto slides or into cell blocks
      by centrifugation. Light microscopy with the May-Grunewald Giemsa stain is
      enhanced, as necessary, by the use of special stains, such as Congo red for
      amyloid, Perl's for iron, Periodic Acid-Schiff for microorganisms, and several
      others. Immunocytological methods enable cell typing, using labels such as CD3
      for T-cells in reactive inflammation; CD20 for B-cells in retinal lymphoma; CD34
      and myeloperoxidase for myeloid leukaemic cells. The polymerase chain reaction
      enhances the identification of organisms in endophthalmitis and of immunoglobulin
      rearrangements in lymphoma. RESULTS: Acquired vitreous opacities can be
      classified according to their aetiology as: genetic; inflammatory non-infectious;
      inflammatory infectious; inflammatory iatrogenic; degenerative, traumatic;
      neoplastic and idiopathic. Non-diagnostic vitreous biopsies, unfortunately, still
      do occur with the main causes of failure including small sample size; sampling
      error; inadequate fixation; and leakage from container during transport.
      CONCLUSIONS: Vitreous biopsy can profoundly influence the outcome in patients
      with vitreous opacities. Success depends on close collaboration between
      clinicians, pathologists and microbiologists. Vitreous samples require proper
      handling and expert application of a wide range of specialized techniques.

PMID- 18344966
TI  - Origin and turnover of ECM proteins from the inner limiting membrane and vitreous
      body.
AB  - The inner limiting membrane (ILM) and the vitreous body (VB) are two major
      extracellular matrix (ECM) structures that are essential for early eye
      development. The ILM is considered to be the basement membrane of the retinal
      neuroepithelium, yet in situ hybridization and chick/quail transplant experiments
      in organ-cultured eyes showed that all components critical for ILM assembly, such
      as laminin or collagen IV, are not synthesized by the retina. Rather, ILM
      proteins, with the exception of agrin, originate from the lens or (and) ciliary
      body and are shed into the vitreous. The VB serves as a reservoir providing high
      concentrations of ILM proteins for the instant assembly of new ILM during rapid
      embryonic eye growth. The function of the retina in ILM assembly is to provide
      the cellular receptor proteins for the binding of the ILM proteins from the
      vitreous. The VB is a gelatinous ECM structure that fills the vitreous cavity of
      the eye. Its major structural proteins, collagen II and fibrillin, originate
      primarily from the ciliary body. Reverse transcription-PCR and western blotting
      show that the rate of synthesis of structural, monomeric ILM and VB proteins,
      such as laminin, collagen IV and II is very high during embryogenesis and very
      low in the adult. The downregulation of ILM and VB protein synthesis occurs
      during early postnatal life, and both ILM and VB are from then on maintained
      throughout life with minimum turnover. Our data explain why ILM and VB do not
      regenerate after vitrectomy and ILM peeling.

PMID- 18344967
TI  - Compensatory head posture and neck problems: is there an association? A cohort
      study of nystagmus patients.
AB  - PURPOSE: The aims of this study were twofold: to investigate if a compensatory
      head posture due to nystagmus causes long-term neck problems or adversely effects
      quality of life and to survey ophthalmologists on their opinions and management
      of these patients. METHODS: A case-controlled study was carried out to assess the
      range of neck movements in patients with compensatory head posture due to
      congenital nystagmus. Exclusion criteria included known neck problems,
      vertebrobasilar insufficiency, and age less than 16 years. Neck movements were
      assessed using an inclinometer. Quality of life and disability was assessed using
      the American Academy of Orthopaedic Surgeons' Cervical Spine Questionnaire. One
      hundred and fifty consultant ophthalmologists throughout the United Kingdom were
      surveyed via a postal questionnaire. RESULTS: The range of motion in these
      patients (n=20) was limited when compared to matched controls especially for
      lateral flexion (P=0.001) and extension (P=0.003). However, despite limited
      movement, patients did not perceive a disability and there was no adverse effect
      on quality of life. In all 55% of ophthalmologists believed compensatory head
      posture due to nystagmus leads to long-term neck problems. About 46% had personal
      experience of patients with long-term neck problems due to nystagmus. Eighty-four
      per cent were influenced in their decision to operate by the presence of a head
      posture. CONCLUSIONS: Significant restriction in neck movements exists in
      nystagmus patients with compensatory head posture, although this does not appear
      to adversely affect quality of life.

PMID- 18344968
TI  - Optical coherence tomographic pattern and focal electroretinogram in patients
      with retinitis pigmentosa.
AB  - PURPOSE: The foveal function of patients with retinitis pigmentosa (RP) has been
      estimated by visual acuity (VA) or visual field (VF) tests. In the present study,
      the potential of optical coherence tomography (OCT) and focal electroretinogram
      (fERG) for monitoring macular function in RP patients was investigated. DESIGN:
      Cross-sectional observational study. METHODS: A total of 56 eyes of 56 patients
      with RP underwent ophthalmic examination including VA, VF, fERG, and OCT.
      Patients were morphologically divided into three groups by the appearance of
      photoreceptor inner/outer segment junction (IS/OS) that were depicted with OCT;
      type 1: no IS/OS visible, type 2: IS/OS was visible but the length was < or =2
      mm, and type 3: IS/OS >2 mm was confirmed. Functional results for VA and fERG
      were compared and analysed based on the three groups. RESULTS: The average VA of
      type 1 patients was significantly lower than that of types 2 or 3 patients
      (P<0.001). There were no significant VA differences detected between types 2 and
      3 patients. While most of the type 1 patients (21/22) showed non-recordable fERG,
      3 out of 18 type 2 patients and none of type 3 patients showed non-recordable
      fERG. Significant differences of the fERG amplitudes were observed among the
      three groups (a-wave, b-wave, and OP, P<0.001 in all three components). However,
      the implicit time showed no difference between type 2 and 3. CONCLUSIONS:
      Analysing the IS/OS with OCT and the amplitudes of fERG may be helpful for
      monitoring RP patients in addition to VA and VF.

PMID- 18344969
TI  - Intravitreal bevacizumab for macular oedema secondary to branch retinal vein
      occlusion.
AB  - PURPOSE: To report short-term results of intravitreal bevacizumab (IVB) injection
      for macular oedema (ME) associated with branch retinal vein occlusion (BRVO).
      METHODS: Retrospective interventional case series of 12 eyes of 12 consecutive
      patients. IVB injections (1.25 mg/0.05 ml) were given as needed based on the
      presence of ME on optical coherence tomography. Changes in Snellen visual acuity
      (VA) and central macular thickness (CMT) were analysed using the Student's paired
      t-test. RESULTS: At a mean follow-up of 9.8 months (range: 6-17 months), the mean
      number of IVB injections given was 4 (range: 1-6). No ocular or systemic side
      effects were noted. The differences in logMAR VA between baseline and 1 month,
      between baseline and 6 months, and between baseline and final follow-up were
      statistically significant (P<0.05). The differences in CMT between baseline and 1
      month, baseline and 6 months, and between baseline and final follow-up were also
      statistically significant (P<0.05). CONCLUSION: Short-term results indicate that
      IVB is useful in decreasing ME and improving VA in eyes with BRVO.

PMID- 18344970
TI  - The Cataract National Dataset Electronic Multi-centre Audit of 55,567 operations:
      anaesthetic techniques and complications.
AB  - PURPOSE: The primary aim of this study was to detail anaesthetic techniques and
      complications for cataract surgery in the UK. METHODS: The Cataract National
      Dataset was extracted from 12 National Health Service Trusts that used the same
      electronic patient record system between November 2001 and July 2006 on a total
      of 55,567 cataract operations. RESULTS: Anaesthesia was administered by an
      ophthalmologist in 56.7% of the cases, a career anaesthetist in 42.1% of the
      cases, a clinical assistant anaesthetist in 0.3% of the cases, and staff were not
      recorded in 0.9% of the cases. Local anaesthesia (LA) was used in 95.5%, with
      topical anaesthesia alone in 22.3% (range by site, 0-99.8%), topical and
      intracameral in 4.7% (range, 0-24.1%), subtenons in 46.9% (range, 0-81.8%),
      peribulbar in 19.5% (range, 0-63.4%), and retrobulbar in 0.5% (range, 0-5.3%).
      One or more minor complications occurred in 4.3% of 38,058 local blocks
      administered by either sharp needle or subtenons (blunt) cannula. Minor
      complications were 2.3 times more common with subtenons blocks (P<0.001). Serious
      complications, defined as sight or life threatening occurred in 25 eyes, 0.066%,
      undergoing sharp needle or subtenons cannula blocks. Sharp needle techniques had
      a 2.5-fold increased risk of serious complications compared with subtenons
      cannula techniques (P=0.026). CONCLUSION: Subtenons anaesthesia was the most
      widely used anaesthetic technique for cataract surgery but wide variation existed
      by site. There was a low rate of reported LA complications. There was a
      statistically significant increased risk of serious complications with sharp
      needle anaesthesia compared with subtenons technique.

PMID- 18344971
TI  - Intravitreal bevacizumab for treatment of choroidal neovascularization secondary
      to angioid streaks.

PMID- 18344972
TI  - Gene induction following wounding of wild-type versus macrophage-deficient
      Drosophila embryos.
AB  - By using a microarray screen to compare gene responses after sterile laser
      wounding of wild-type and 'macrophageless' serpent mutant Drosophila embryos, we
      show the wound-induced programmes that are independent of a pathogenic response
      and distinguish which of the genes are macrophage dependent. The evolutionarily
      conserved nature of this response is highlighted by our finding that one such new
      inflammation-associated gene, growth arrest and DNA damage-inducible gene 45
      (GADD45), is upregulated in both Drosophila and murine repair models. Comparison
      of unwounded wild-type and serpent mutant embryos also shows a portfolio of
      'macrophage-specific' genes, which suggest analogous functions with vertebrate
      inflammatory cells. Besides identifying the various classes of wound- and
      macrophage-related genes, our data indicate that sterile injury per se, in the
      absence of pathogens, triggers induction of a 'pathogen response', which might
      prime the organism for what is likely to be an increased risk of infection.

PMID- 18344973
TI  - Lentivector-mediated rescue from cerebellar ataxia in a mouse model of
      spinocerebellar ataxia.
AB  - Polyglutamine disorders are inherited neurodegenerative diseases caused by the
      accumulation of expanded polyglutamine protein (polyQ). Previously, we identified
      a new guanosine triphosphatase, CRAG, which facilitates the degradation of polyQ
      aggregates through the ubiquitin-proteasome pathway in cultured cells. Because
      expression of CRAG decreases in the adult brain, a reduced level of CRAG could
      underlie the onset of polyglutamine diseases. To examine the potential of CRAG
      expression for treating polyglutamine diseases, we generated model mice
      expressing polyQ predominantly in Purkinje cells. The model mice showed poor
      dendritic arborization of Purkinje cells, a markedly atrophied cerebellum and
      severe ataxia. Lentivector-mediated expression of CRAG in Purkinje cells of model
      mice extensively cleared polyQ aggregates and re-activated dendritic
      differentiation, resulting in a striking rescue from ataxia. Our in vivo data
      substantiate previous cell-culture-based results and extend further the
      usefulness of targeted delivery of CRAG as a gene therapy for polyglutamine
      diseases.

PMID- 18344974
TI  - Clathrin-independent endocytosis used by the IL-2 receptor is regulated by Rac1,
      Pak1 and Pak2.
AB  - There are several endocytic pathways, which are either dependent on or
      independent of clathrin. This study focuses on a poorly characterized mechanism
      clathrin- and caveolae-independent endocytosis-used by the interleukin-2 receptor
      beta (IL-2R beta). We address the question of its regulation in comparison with
      the clathrin-dependent pathway. First, we show that Ras-related C3 botulinum
      toxin substrate 1 (Rac1) is specifically required for IL-2R beta entry, and we
      identify p21-activated kinases (Paks) as downstream targets. By RNA interference,
      we show that Pak1 and Pak2 are both necessary for IL-2R beta uptake, in contrast
      to the clathrin-dependent route. We observe that cortactin, a partner of actin
      and dynamin-two essential endocytic factors-is required for IL-2R beta uptake.
      Furthermore, we find that cortactin acts downstream from Paks, suggesting control
      of its function by these kinases. Thus, we describe a cascade composed of Rac1,
      Paks and cortactin specifically regulating IL-2R beta internalization. This study
      indicates Paks as the first specific regulators of the clathrin-independent
      endocytosis pathway.

PMID- 18344975
TI  - Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor.
AB  - G-protein-coupled receptors (GPCRs) respond to external stimuli by activating
      heterotrimeric G proteins inside the cell. There is increasing evidence that many
      GPCRs exist as dimers or higher oligomers, but the biochemical nature of such
      dimers and what roles they have, if any, in signal transduction remains unclear.
      We conducted a comprehensive study of dimerization of the 5HT2c serotonin
      receptor using disulphide-trapping experiments. We found a dimer interface
      between transmembrane (TM) helices IV and V that is markedly sensitive to the
      state of receptor activation. This dimer seems to be quasisymmetrical in
      interfacial geometry and asymmetrical in its association with its cognate G alpha
      protein. We also found a second interface at TM I helices, which is insensitive
      to the state of activation.

PMID- 18344976
TI  - Expression of prostate-specific membrane antigen in renal cortical tumors.
AB  - Prostate-specific membrane antigen is a type II membrane glycoprotein that is
      expressed in benign and neoplastic prostatic tissue and has been recently shown
      to be also expressed in the neovasculature of various solid malignant tumors
      including renal cell carcinoma. Renal cell carcinoma is a heterogeneous group of
      tumors with distinct morphologic and genetic characteristics and clinical
      behaviors. We performed immunohistochemical studies on formalin-fixed, paraffin
      embedded archival material from 75 nephrectomies, using antibodies 13D6 against
      prostate-specific membrane antigen and CD31 against endothelial cells. The study
      included 30 clear cell renal cell carcinomas, and 15 of each of papillary and
      chromophobe renal cell carcinoma and oncocytoma. The extent and intensity of
      staining were assessed semiquantitatively. In all cases, immunoreactivity was
      detected only in the tumor-associated neovasculature and not in tumor cells.
      Clear cell renal cell carcinoma showed the most diffuse staining pattern, where
      24/30 cases or 80% had >50% reactive vessels, followed by chromophobe renal cell
      carcinoma (9/15; 60%) and oncocytoma (5/15, 33%). No diffuse staining was
      detected in any of the papillary renal cell carcinomas and only focal staining
      was detected in 11 cases (11/15; 73%). Staining intensity was the strongest in
      clear cell renal cell carcinoma (25/30; 83%) followed by chromophobe renal cell
      carcinoma (9/15; 60%), oncocytoma (8/15, 53%) and papillary renal cell carcinoma
      (5/15; 33%). In summary, prostate-specific membrane antigen is expressed in tumor
      associated neovasculature of the majority of renal cortical tumors and is most
      diffusely and intensely expressed in clear cell renal cell carcinoma and least in
      papillary renal cell carcinoma. The differences in the expression of prostate
      specific membrane antigen in renal cell carcinoma subtypes provide further
      evidence of the biological diversity of these tumors, and diagnostic and
      therapeutic applications of such expression can be expanded to include subtypes
      of renal cell carcinoma.

PMID- 18344977
TI  - NFkappaB selectivity of estrogen receptor ligands revealed by comparative
      crystallographic analyses.
AB  - Our understanding of how steroid hormones regulate physiological functions has
      been significantly advanced by structural biology approaches. However, progress
      has been hampered by misfolding of the ligand binding domains in heterologous
      expression systems and by conformational flexibility that interferes with
      crystallization. Here, we show that protein folding problems that are common to
      steroid hormone receptors are circumvented by mutations that stabilize well
      characterized conformations of the receptor. We use this approach to present the
      structure of an apo steroid receptor that reveals a ligand-accessible channel
      allowing soaking of preformed crystals. Furthermore, crystallization of different
      pharmacological classes of compounds allowed us to define the structural basis of
      NFkappaB-selective signaling through the estrogen receptor, thus revealing a
      unique conformation of the receptor that allows selective suppression of
      inflammatory gene expression. The ability to crystallize many receptor-ligand
      complexes with distinct pharmacophores allows one to define structural features
      of signaling specificity that would not be apparent in a single structure.

PMID- 18344978
TI  - Lateral presynaptic inhibition mediates gain control in an olfactory circuit.
AB  - Olfactory signals are transduced by a large family of odorant receptor proteins,
      each of which corresponds to a unique glomerulus in the first olfactory relay of
      the brain. Crosstalk between glomeruli has been proposed to be important in
      olfactory processing, but it is not clear how these interactions shape the odour
      responses of second-order neurons. In the Drosophila antennal lobe (a region
      analogous to the vertebrate olfactory bulb), we selectively removed most
      interglomerular input to genetically identified second-order olfactory neurons.
      Here we show that this broadens the odour tuning of these neurons, implying that
      interglomerular inhibition dominates over interglomerular excitation. The
      strength of this inhibitory signal scales with total feedforward input to the
      entire antennal lobe, and has similar tuning in different glomeruli. A
      substantial portion of this interglomerular inhibition acts at a presynaptic
      locus, and our results imply that this is mediated by both ionotropic and
      metabotropic receptors on the same nerve terminal.

PMID- 18344979
TI  - A neural representation of depth from motion parallax in macaque visual cortex.
AB  - Perception of depth is a fundamental challenge for the visual system,
      particularly for observers moving through their environment. The brain makes use
      of multiple visual cues to reconstruct the three-dimensional structure of a
      scene. One potent cue, motion parallax, frequently arises during translation of
      the observer because the images of objects at different distances move across the
      retina with different velocities. Human psychophysical studies have demonstrated
      that motion parallax can be a powerful depth cue, and motion parallax seems to be
      heavily exploited by animal species that lack highly developed binocular vision.
      However, little is known about the neural mechanisms that underlie this capacity.
      Here we show, by using a virtual-reality system to translate macaque monkeys
      (Macaca mulatta) while they viewed motion parallax displays that simulated
      objects at different depths, that many neurons in the middle temporal area (area
      MT) signal the sign of depth (near versus far) from motion parallax in the
      absence of other depth cues. To achieve this, neurons must combine visual motion
      with extra-retinal (non-visual) signals related to the animal's movement. Our
      findings suggest a new neural substrate for depth perception and demonstrate a
      robust interaction of visual and non-visual cues in area MT. Combined with
      previous studies that implicate area MT in depth perception based on binocular
      disparities, our results suggest that area MT contains a more general
      representation of three-dimensional space that makes use of multiple cues.

PMID- 18344980
TI  - Tumour maintenance is mediated by eNOS.
AB  - Tumour cells become addicted to the expression of initiating oncogenes like Ras,
      such that loss of oncogene expression in established tumours leads to tumour
      regression. HRas, NRas or KRas are mutated to remain in the active GTP-bound
      oncogenic state in many cancers. Although Ras activates several proteins to
      initiate human tumour growth, only PI3K, through activation of protein kinase B
      (PKB; also known as AKT), must remain activated by oncogenic Ras to maintain this
      growth. Here we show that blocking phosphorylation of the AKT substrate,
      endothelial nitric oxide synthase (eNOS or NOS3), inhibits tumour initiation and
      maintenance. Moreover, eNOS enhances the nitrosylation and activation of
      endogenous wild-type Ras proteins, which are required throughout tumorigenesis.
      We suggest that activation of the PI3K-AKT-eNOS-(wild-type) Ras pathway by
      oncogenic Ras in cancer cells is required to initiate and maintain tumour growth.

PMID- 18344981
TI  - Genetics of gene expression and its effect on disease.
AB  - Common human diseases result from the interplay of many genes and environmental
      factors. Therefore, a more integrative biology approach is needed to unravel the
      complexity and causes of such diseases. To elucidate the complexity of common
      human diseases such as obesity, we have analysed the expression of 23,720
      transcripts in large population-based blood and adipose tissue cohorts
      comprehensively assessed for various phenotypes, including traits related to
      clinical obesity. In contrast to the blood expression profiles, we observed a
      marked correlation between gene expression in adipose tissue and obesity-related
      traits. Genome-wide linkage and association mapping revealed a highly significant
      genetic component to gene expression traits, including a strong genetic effect of
      proximal (cis) signals, with 50% of the cis signals overlapping between the two
      tissues profiled. Here we demonstrate an extensive transcriptional network
      constructed from the human adipose data that exhibits significant overlap with
      similar network modules constructed from mouse adipose data. A core network
      module in humans and mice was identified that is enriched for genes involved in
      the inflammatory and immune response and has been found to be causally associated
      to obesity-related traits.

PMID- 18344982
TI  - Variations in DNA elucidate molecular networks that cause disease.
AB  - Identifying variations in DNA that increase susceptibility to disease is one of
      the primary aims of genetic studies using a forward genetics approach. However,
      identification of disease-susceptibility genes by means of such studies provides
      limited functional information on how genes lead to disease. In fact, in most
      cases there is an absence of functional information altogether, preventing a
      definitive identification of the susceptibility gene or genes. Here we develop an
      alternative to the classic forward genetics approach for dissecting complex
      disease traits where, instead of identifying susceptibility genes directly
      affected by variations in DNA, we identify gene networks that are perturbed by
      susceptibility loci and that in turn lead to disease. Application of this method
      to liver and adipose gene expression data generated from a segregating mouse
      population results in the identification of a macrophage-enriched network
      supported as having a causal relationship with disease traits associated with
      metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl),
      lactamase beta (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as
      previously unknown obesity genes, strengthening the association between this
      network and metabolic disease traits. Our analysis provides direct experimental
      support that complex traits such as obesity are emergent properties of molecular
      networks that are modulated by complex genetic loci and environmental factors.

PMID- 18344983
TI  - NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration.
AB  - Neurodegeneration can be triggered by genetic or environmental factors. Although
      the precise cause is often unknown, many neurodegenerative diseases share common
      features such as protein aggregation and age dependence. Recent studies in
      Drosophila have uncovered protective effects of NAD synthase nicotinamide
      mononucleotide adenylyltransferase (NMNAT) against activity-induced
      neurodegeneration and injury-induced axonal degeneration. Here we show that NMNAT
      overexpression can also protect against spinocerebellar ataxia 1 (SCA1)-induced
      neurodegeneration, suggesting a general neuroprotective function of NMNAT. It
      protects against neurodegeneration partly through a proteasome-mediated pathway
      in a manner similar to heat-shock protein 70 (Hsp70). NMNAT displays chaperone
      function both in biochemical assays and cultured cells, and it shares significant
      structural similarity with known chaperones. Furthermore, it is upregulated in
      the brain upon overexpression of poly-glutamine expanded protein and recruited
      with the chaperone Hsp70 into protein aggregates. Our results implicate NMNAT as
      a stress-response protein that acts as a chaperone for neuronal maintenance and
      protection. Our studies provide an entry point for understanding how normal
      neurons maintain activity, and offer clues for the common mechanisms underlying
      different neurodegenerative conditions.

PMID- 18344984
TI  - Drosophila STAT is required for directly maintaining HP1 localization and
      heterochromatin stability.
AB  - STAT (Signal transducer and activator of transcription) is a potent transcription
      factor and its aberrant activation by phosphorylation is associated with human
      cancers. We have shown previously that overactivation of JAK, which
      phosphorylates STAT, disrupts heterochromatin formation globally in Drosophila
      melanogaster. However, it remains unclear how this effect is mediated and whether
      STAT is involved. Here, we demonstrate that Drosophila STAT (STAT92E) is involved
      in controlling heterochromatin protein 1 (HP1) distribution and heterochromatin
      stability. We found, unexpectedly, that loss of STAT92E, had the same effects as
      overactivation of JAK in disrupting heterochromatin formation and heterochromatic
      gene silencing, whereas overexpression of STAT92E had the opposite effects. We
      have further shown that the unphosphorylated or 'transcriptionally inactive' form
      of STAT92E is localized on heterochromatin in association with HP1, and is
      required for stabilizing HP1 localization and histone H3 Lys 9 methylation
      (H3mK9) . However, activation by phosphorylation reduces heterochromatin
      associated STAT92E, causing HP1 displacement and heterochromatin destabilization.
      Thus, reducing levels of unphosphorylated STAT92E, either by loss of STAT92E or
      increased phosphorylation, causes heterochromatin instability. These results
      suggest that activation of STAT by phosphorylation controls both access to
      chromatin and activity of the transcription machinery.

PMID- 18344985
TI  - Monoubiquitinated H2B is associated with the transcribed region of highly
      expressed genes in human cells.
AB  - Histone modifications have emerged as important regulators of transcription.
      Histone H2B monoubiquitination has also been implicated in transcription;
      however, better understanding of the biological significance of this modification
      in mammalian cells has been hindered by the lack of suitable reagents,
      particularly antibodies capable of specifically recognizing ubiquitinated H2B
      (ubH2B). Here, we report the generation of anti-ubH2B monoclonal antibodies using
      a branched peptide as immunogen. These antibodies provide a powerful tool for
      exploring the biochemical functions of H2B monoubiquitination at both a genome
      wide and gene-specific level. Application of these antibodies in high resolution
      chromatin immunoprecipitation (ChIP)-chip experiments in human cells, using
      tiling arrays, revealed preferential association of ubiquitinated H2B with the
      transcribed regions of highly expressed genes. Unlike dimethylated H3K4, ubH2B
      was not associated with distal promoter regions. Furthermore, experimental
      modulation of the transcriptional activity of the tumour suppressor p53 was
      accompanied by rapid changes in the H2B ubiquitination status of its p21 target
      gene, attesting to the dynamic nature of this process. It has recently been
      demonstrated that the apparent extent of gene expression often reflects
      elongation rather than initiation rates; thus, our findings suggest that H2B
      ubiquitination is intimately linked with global transcriptional elongation in
      mammalian cells.

PMID- 18344986
TI  - Drosophila short neuropeptide F signalling regulates growth by ERK-mediated
      insulin signalling.
AB  - Insulin and insulin growth factor have central roles in growth, metabolism and
      ageing of animals, including Drosophila melanogaster. In Drosophila, insulin-like
      peptides (Dilps) are produced by specialized neurons in the brain. Here we show
      that Drosophila short neuropeptide F (sNPF), an orthologue of mammalian
      neuropeptide Y (NPY), and sNPF receptor sNPFR1 regulate expression of Dilps. Body
      size was increased by overexpression of sNPF or sNPFR1. The fat body of sNPF
      mutant Drosophila had downregulated Akt, nuclear localized FOXO, upregulated
      translational inhibitor 4E-BP and reduced cell size. Circulating levels of
      glucose were elevated and lifespan was also extended in sNPF mutants. We show
      that these effects are mediated through activation of extracellular signal
      related kinases (ERK) in insulin-producing cells of larvae and adults. Insulin
      expression was also increased in an ERK-dependent manner in cultured Drosophila
      central nervous system (CNS) cells and in rat pancreatic cells treated with sNPF
      or NPY peptide, respectively. Drosophila sNPF and the evolutionarily conserved
      mammalian NPY seem to regulate ERK-mediated insulin expression and thus to
      systemically modulate growth, metabolism and lifespan.

PMID- 18344987
TI  - Functional interaction between FOXO3a and ATM regulates DNA damage response.
AB  - The maintenance of genomic stability in cells is relentlessly challenged by
      environmental stresses that induce DNA breaks, which activate the DNA-damage
      pathway mediated by ataxia-telangiectasia mutated (ATM) and its downstream
      mediators to control damage-induced cell-cycle checkpoints and DNA repair. Here,
      we show that FOXO3a interacts with ATM to promote phosphorylation of ATM at Ser
      1981 and prompting its downstream mediators to form nuclear foci in response to
      DNA damage. Silencing FOXO3a in cells abrogates the formation of ATM-pS1981 and
      phospho-histone H2AX foci after DNA damage. Increasing FOXO3a in cells promotes
      ATM-regulated signalling, the intra-S-phase or G2-M cell-cycle checkpoints, and
      the repair of damaged DNA, whereas cells lacking FOXO3a did not trigger the DNA
      repair mechanism after DNA damage. The carboxy-terminal domain of FOXO3a binds to
      the FAT domain of ATM, thereby contributing to the activation of ATM. These
      results suggest that ATM may be regulated directly by FOXO3a in the DNA-damage
      response.

PMID- 18344988
TI  - Inn1 couples contraction of the actomyosin ring to membrane ingression during
      cytokinesis in budding yeast.
AB  - By rapidly depleting each of the essential budding yeast proteins of unknown
      function, we identified a novel factor that we call Inn1, which associates with
      the contractile actomyosin ring at the end of mitosis and is needed for
      cytokinesis. We show that Inn1 has a C2 domain at the amino terminus of the
      protein that is required for ingression of the plasma membrane, whereas the
      remainder of the protein recruits Inn1 to the actomyosin ring. The lethal effects
      of deleting the INN1 gene can be suppressed by artificial fusion of the C2 domain
      to other components of the actomyosin ring, restoring membrane ingression on
      contraction of the actomyosin ring. Our data indicate that recruitment of the C2
      domain of Inn1 to the contractile actomyosin ring is crucial for ingression of
      the plasma membrane during cytokinesis in budding yeast.

PMID- 18344989
TI  - Sirt1 contributes critically to the redox-dependent fate of neural progenitors.
AB  - Repair processes that are activated in response to neuronal injury, be it
      inflammatory, ischaemic, metabolic, traumatic or other cause, are characterized
      by a failure to replenish neurons and by astrogliosis. The underlying molecular
      pathways, however, are poorly understood. Here, we show that subtle alterations
      of the redox state, found in different brain pathologies, regulate the fate of
      mouse neural progenitor cells (NPCs) through the histone deacetylase (HDAC)
      Sirt1. Mild oxidation or direct activation of Sirt1 suppressed proliferation of
      NPCs and directed their differentiation towards the astroglial lineage at the
      expense of the neuronal lineage, whereas reducing conditions had the opposite
      effect. Under oxidative conditions in vitro and in vivo, Sirt1 was upregulated in
      NPCs, bound to the transcription factor Hes1 and subsequently inhibited pro
      neuronal Mash1. In utero shRNA-mediated knockdown of Sirt1 in NPCs prevented
      oxidation-mediated suppression of neurogenesis and caused upregulation of Mash1
      in vivo. Our results provide evidence for an as yet unknown metabolic master
      switch that determines the fate of neural progenitors.

PMID- 18344990
TI  - Development and spike timing-dependent plasticity of recurrent excitation in the
      Xenopus optic tectum.
AB  - Much of the information processing in the brain occurs at the level of local
      circuits; however, the mechanisms underlying their initial development are poorly
      understood. We sought to examine the early development and plasticity of local
      excitatory circuits in the optic tectum of Xenopus laevis tadpoles. We found that
      retinal input recruits persistent, recurrent intratectal synaptic excitation that
      becomes more temporally compact and less variable over development, thus
      increasing the temporal coherence and precision of tectal cell spiking. We also
      saw that patterned retinal input can sculpt recurrent activity according to a
      spike timing-dependent plasticity rule, and that impairing this plasticity during
      development results in abnormal refinement of the temporal characteristics of
      recurrent circuits. This plasticity is a previously unknown mechanism by which
      patterned retinal activity allows intratectal circuitry to self-organize,
      optimizing the temporal response properties of the tectal network, and provides a
      substrate for rapid modulation of tectal neuron receptive-field properties.

PMID- 18344991
TI  - Compartment-specific transcription factors orchestrate angiogenesis gradients in
      the embryonic brain.
AB  - Prevailing notions of cerebral vascularization imply that blood vessels sprout
      passively into the brain parenchyma from pial vascular plexuses to meet metabolic
      needs of growing neuronal populations. Endothelial cells, building blocks of
      blood vessels, are thought to be homogeneous in the brain with respect to their
      origins, gene expression patterns and developmental mechanisms. These current
      notions that cerebral angiogenesis is regulated by local environmental signals
      contrast with current models of cell-autonomous regulation of neuronal
      development. Here we demonstrate that telencephalic angiogenesis in mice
      progresses in an orderly, ventral-to-dorsal gradient regulated by compartment
      specific homeobox transcription factors. Our data offer new perspectives on
      intrinsic regulation of angiogenesis in the embryonic telencephalon, call for a
      revision of the current models of telencephalic angiogenesis and support novel
      roles for endothelial cells in brain development.

PMID- 18344992
TI  - ALS-causing SOD1 mutants generate vascular changes prior to motor neuron
      degeneration.
AB  - We report here that amyotrophic lateral sclerosis-linked superoxide dismutase 1
      (SOD1) mutants with different biochemical characteristics disrupted the blood
      spinal cord barrier in mice by reducing the levels of the tight junction proteins
      ZO-1, occludin and claudin-5 between endothelial cells. This resulted in
      microhemorrhages with release of neurotoxic hemoglobin-derived products,
      reductions in microcirculation and hypoperfusion. SOD1 mutant-mediated
      endothelial damage accumulated before motor neuron degeneration and the
      neurovascular inflammatory response occurred, indicating that it was a central
      contributor to disease initiation.

PMID- 18344993
TI  - The evolution of the arcuate fasciculus revealed with comparative DTI.
AB  - The arcuate fasciculus is a white-matter fiber tract that is involved in human
      language. Here we compared cortical connectivity in humans, chimpanzees and
      macaques (Macaca mulatta) and found a prominent temporal lobe projection of the
      human arcuate fasciculus that is much smaller or absent in nonhuman primates.
      This human specialization may be relevant to the evolution of language.

PMID- 18344994
TI  - Synaptic NMDA receptor activity boosts intrinsic antioxidant defenses.
AB  - Intrinsic antioxidant defenses are important for neuronal longevity. We found
      that in rat neurons, synaptic activity, acting via NMDA receptor (NMDAR)
      signaling, boosted antioxidant defenses by making changes to the thioredoxin
      peroxiredoxin (Prx) system. Synaptic activity enhanced thioredoxin activity,
      facilitated the reduction of overoxidized Prxs and promoted resistance to
      oxidative stress. Resistance was mediated by coordinated transcriptional changes;
      synaptic NMDAR activity inactivated a previously unknown Forkhead box O target
      gene, the thioredoxin inhibitor Txnip. Conversely, NMDAR blockade upregulated
      Txnip in vivo and in vitro, where it bound thioredoxin and promoted vulnerability
      to oxidative damage. Synaptic activity also upregulated the Prx reactivating
      genes Sesn2 (sestrin 2) and Srxn1 (sulfiredoxin), via C/EBPbeta and AP-1,
      respectively. Mimicking these expression changes was sufficient to strengthen
      antioxidant defenses. Trans-synaptic stimulation of synaptic NMDARs was crucial
      for boosting antioxidant defenses; chronic bath activation of all (synaptic and
      extrasynaptic) NMDARs induced no antioxidative effects. Thus, synaptic NMDAR
      activity may influence the progression of pathological processes associated with
      oxidative damage.

PMID- 18344995
TI  - Persistent restoration of sensory function by immediate or delayed systemic
      artemin after dorsal root injury.
AB  - Dorsal root injury results in substantial and often irreversible loss of sensory
      functions as a result of the limited regenerative capacity of sensory axons and
      the inhibitory barriers that prevent both axonal entry into and regeneration in
      the spinal cord. Here, we describe previously unknown effects of the growth
      factor artemin after crush injury of the dorsal spinal nerve roots in rats.
      Artemin not only promoted re-entry of multiple classes of sensory fibers into the
      spinal cord and re-establishment of synaptic function and simple behavior, but it
      also, surprisingly, promoted the recovery of complex behavior. These effects
      occurred after a 2-week schedule of intermittent, systemic administration of
      artemin and persisted for at least 6 months following treatment, suggesting a
      substantial translational advantage. Systemic artemin administration produced
      essentially complete and persistent restoration of nociceptive and sensorimotor
      functions, and could represent a promising therapy that may effectively promote
      sensory neuronal regeneration and functional recovery after injury.

PMID- 18344996
TI  - Emotional environments retune the valence of appetitive versus fearful functions
      in nucleus accumbens.
AB  - The nucleus accumbens mediates both appetitive motivation for rewards and fearful
      motivation toward threats, which are generated in part by glutamate-related
      circuits organized in a keyboard fashion. At rostral sites of the medial shell,
      localized glutamate disruptions typically generate intense appetitive behaviors
      in rats, but the disruption incrementally generates fearful behaviors as
      microinjection sites move more caudally. We found that exposure to stressful
      environments caused caudal fear-generating zones to expand rostrally, filling
      approximately 90% of the shell. Conversely, a preferred home environment caused
      fear-generating zones to shrink and appetitive-generating zones to expand
      caudally, filling approximately 90% of the shell. Thus, the emotional
      environments retuned the generation of motivation in corticolimbic circuits.

PMID- 18344997
TI  - Redefining the serotonergic system by genetic lineage.
AB  - Central serotonin-producing neurons are heterogeneous-differing in location,
      morphology, neurotoxin sensitivity and associated clinical disorders-but the
      underpinnings of this heterogeneity are largely unknown, as are the markers that
      distinguish physiological subtypes of serotonergic neurons. Here we redefined
      serotonergic subtypes on the basis of genetic programs that are differentially
      enacted in progenitor cells. We uncovered a molecular framework for the
      serotonergic system that, having genetic lineages as its basis, is likely to have
      physiological relevance and will permit access to genetically defined subtypes
      for manipulation.

PMID- 18344998
TI  - Highly effective SNP-based association mapping and management of recessive
      defects in livestock.
AB  - The widespread use of elite sires by means of artificial insemination in
      livestock breeding leads to the frequent emergence of recessive genetic defects,
      which cause significant economic and animal welfare concerns. Here we show that
      the availability of genome-wide, high-density SNP panels, combined with the
      typical structure of livestock populations, markedly accelerates the positional
      identification of genes and mutations that cause inherited defects. We report the
      fine-scale mapping of five recessive disorders in cattle and the molecular basis
      for three of these: congenital muscular dystony (CMD) types 1 and 2 in Belgian
      Blue cattle and ichthyosis fetalis in Italian Chianina cattle. Identification of
      these causative mutations has an immediate translation into breeding practice,
      allowing marker assisted selection against the defects through avoidance of at
      risk matings.

PMID- 18344999
TI  - Transient-mediated fate determination in a transcriptional circuit of HIV.
AB  - Steady-state behavior and bistability have been proposed as mechanisms for
      decision making in gene circuits. However, transient gene expression has also
      been proposed to control cell fate, with the decision arbitrated by the duration
      of a transient gene expression pulse. Here, using an HIV-1 model system, we
      directly quantify transcriptional feedback strength and its effects on both the
      duration of HIV-1 Tat transcriptional pulses and the fate of HIV-infected cells.
      By measuring shifts in the autocorrelation of noise inherent to gene expression,
      we found that transcriptional positive feedback extends the single-cell Tat
      expression lifetime two- to sixfold for both minimal Tat circuits and full
      length, actively replicating HIV-1. Notably, artificial weakening of Tat positive
      feedback shortened the duration of Tat expression transients and biased the
      probability in favor of latency. Thus, transcriptional positive feedback can
      modulate transient expression lifetime to a greater extent than protein half-life
      modulation, and it has a critical role in the cell-fate decision in HIV.

PMID- 18345000
TI  - A mutation of human cytochrome c enhances the intrinsic apoptotic pathway but
      causes only thrombocytopenia.
AB  - We report the first identified mutation in the gene encoding human cytochrome c
      (CYCS). Glycine 41, invariant throughout eukaryotes, is substituted by serine in
      a family with autosomal dominant thrombocytopenia caused by dysregulated platelet
      formation. The mutation yields a cytochrome c variant with enhanced apoptotic
      activity in vitro. Notably, the family has no other phenotypic indication of
      abnormal apoptosis, implying that cytochrome c activity is not a critical
      regulator of most physiological apoptosis.

PMID- 18345001
TI  - TRIM30 alpha negatively regulates TLR-mediated NF-kappa B activation by targeting
      TAB2 and TAB3 for degradation.
AB  - Toll-like receptor (TLR) signaling is pivotal to innate and adaptive immune
      responses and must be tightly controlled. The mechanisms of TLR signaling have
      been the focus of extensive studies. Here we report that the tripartite-motif
      protein TRIM30alpha, a RING protein, was induced by TLR agonists and interacted
      with the TAB2-TAB3-TAK1 adaptor-kinase complex involved in the activation of
      transcription factor NF-kappaB. TRIM30alpha promoted the degradation of TAB2 and
      TAB3 and inhibited NF-kappaB activation induced by TLR signaling. In vivo studies
      showed that transfected or transgenic mice overexpressing TRIM30alpha were more
      resistant to endotoxic shock. Consistent with that, in vivo 'knockdown' of
      TRIM30alpha mRNA by small interfering RNA impaired lipopolysaccharide-induced
      tolerance. Finally, expression of TRIM30alpha depended on NF-kappaB activation.
      Our results collectively indicate that TRIM30alpha negatively regulates TLR
      mediated NF-kappaB activation by targeting degradation of TAB2 and TAB3 by a
      'feedback' mechanism.

PMID- 18345002
TI  - TNF activates an IRF1-dependent autocrine loop leading to sustained expression of
      chemokines and STAT1-dependent type I interferon-response genes.
AB  - Rapid induction of inflammatory genes by tumor necrosis factor (TNF) has been
      well studied, but little is known about delayed and chronic TNF responses. Here
      we investigated the kinetics of primary macrophage responses to TNF and
      discovered that TNF initiates an interferon-beta-mediated autocrine loop that
      sustains expression of inflammatory genes and induces delayed expression of
      interferon-response genes such as those encoding the transcription factors STAT1
      and IRF7, which enhance macrophage responses to stimulation of cytokines and Toll
      like receptors. TNF-induced interferon-beta production depended on interferon
      response factor 1, and downstream gene expression was mediated by synergy between
      small amounts of interferon-beta and canonical TNF-induced signals. Thus, TNF
      activates a 'feed-forward' loop that sustains inflammation but avoids the
      potential toxicity associated with the high interferon production induced by
      stimulation of Toll-like receptors.

PMID- 18345003
TI  - Regulation of T cell survival through coronin-1-mediated generation of inositol
      1,4,5-trisphosphate and calcium mobilization after T cell receptor triggering.
AB  - T cell homeostasis is essential for the functioning of the vertebrate immune
      system, but the intracellular signals required for T cell homeostasis are largely
      unknown. We here report that the WD-repeat protein family member coronin-1,
      encoded by the gene Coro1a, is essential in the mouse for T cell survival through
      its promotion of Ca2+ mobilization from intracellular stores. Upon T cell
      receptor triggering, coronin-1 was essential for the generation of inositol-1,4,5
      trisphosphate from phosphatidylinositol-4,5-bisphosphate. The absence of coronin
      1, although it did not affect T cell development, resulted in a profound defect
      in Ca2+ mobilization, interleukin-2 production, T cell proliferation and T cell
      survival. We conclude that coronin-1, through activation of Ca2+ release from
      intracellular stores, is an essential regulator of peripheral lymphocyte
      survival.

PMID- 18345004
TI  - Ru-Pt core-shell nanoparticles for preferential oxidation of carbon monoxide in
      hydrogen.
AB  - Most of the world's hydrogen supply is currently obtained by reforming
      hydrocarbons. 'Reformate' hydrogen contains significant quantities of CO that
      poison current hydrogen fuel-cell devices. Catalysts are needed to remove CO from
      hydrogen through selective oxidation. Here, we report first-principles-guided
      synthesis of a nanoparticle catalyst comprising a Ru core covered with an
      approximately 1-2-monolayer-thick shell of Pt atoms. The distinct catalytic
      properties of these well-characterized core-shell nanoparticles were demonstrated
      for preferential CO oxidation in hydrogen feeds and subsequent hydrogen light
      off. For H2 streams containing 1,000 p.p.m. CO, H2 light-off is complete by 30
      (composite function)C, which is significantly better than for traditional PtRu
      nano-alloys (85 (composite function)C), monometallic mixtures of nanoparticles
      (93 (composite function)C) and pure Pt particles (170 ( composite function)C).
      Density functional theory studies suggest that the enhanced catalytic activity
      for the core-shell nanoparticle originates from a combination of an increased
      availability of CO-free Pt surface sites on the Ru@Pt nanoparticles and a
      hydrogen-mediated low-temperature CO oxidation process that is clearly distinct
      from the traditional bifunctional CO oxidation mechanism.

PMID- 18345005
TI  - In vivo immunogold labeling confirms large-scale chromatin folding motifs.
AB  - The difficulty in localizing specific cellular proteins by immuno-electron
      microscopy techniques limits applications of electron microscopy to cell biology.
      We found that in vivo immunogold labeling improves epitope accessibility,
      ultrastructural preservation and three-dimensional visualization, and allows
      correlated light and electron microscopy. We detected large-scale chromatin
      folding motifs within intact interphase nuclei of CHO cells and visualized the
      ultrastructure of DNA replication 'factories' labeled with GFP-proliferating cell
      nuclear antigen (PCNA).

PMID- 18345006
TI  - A quantitative analysis software tool for mass spectrometry-based proteomics.
AB  - We describe Census, a quantitative software tool compatible with many labeling
      strategies as well as with label-free analyses, single-stage mass spectrometry
      (MS1) and tandem mass spectrometry (MS/MS) scans, and high- and low-resolution
      mass spectrometry data. Census uses robust algorithms to address poor-quality
      measurements and improve quantitative efficiency, and it can support several
      input file formats. We tested Census with stable-isotope labeling analyses as
      well as label-free analyses.

PMID- 18345007
TI  - Genome-wide mapping of allele-specific protein-DNA interactions in human cells.
AB  - We describe a high-throughput method, named ChIP-SNP, for the identification of
      allele-specific protein-DNA interactions throughout the human genome. ChIP-SNP
      combines chromatin immunoprecipitation (ChIP) with whole-genome single nucleotide
      polymorphism (SNP) genotyping microarray analysis. We demonstrated that it can be
      used to accurately identify allele-specific binding of RNA polymerase II (RNAP)
      in the human fibroblast genome, uncovering imprinted genes and other allele
      specific binding events. ChIP-SNP will facilitate the study of mechanisms of
      allele-specific gene expression.

PMID- 18345008
TI  - Direct measurement of protein dynamics inside cells using a rationally designed
      photoconvertible protein.
AB  - All biological reactions depend on the diffusion and re-localization of
      biomolecules. Our understanding of biological processes requires accurate
      measurement of biomolecule mobility in living cells. Currently, approaches for
      investigating the mobility of biomolecules are generally restricted to measuring
      either fast or slow diffusion kinetics. We describe the development and
      application of a photoconvertible fluorescent protein, Phamret, that can be
      highlighted by UV light stimulation inducing a change in fluorescence emission
      from cyan fluorescent protein (CFP) to photoactivated GFP (PA-GFP). Phamret can
      be monitored by single excitation-dual emission mode for visualization of
      molecular dynamics for a broad range of kinetics. We also devised a microscopy
      based method to measure the diffusion coefficient from the fluorescence decay
      after photostimulation of Phamret, enabling analysis of diffusion kinetics
      ranging from less than 0.1 microm2/s up to approximately 100 microm2/s, and found
      significant changes in free protein movement during cell-cycle progression.

PMID- 18345009
TI  - Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and
      endothelial hyperpermeability.
AB  - The angiogenic sprout has been compared to the growing axon, and indeed, many
      proteins direct pathfinding by both structures. The Roundabout (Robo) proteins
      are guidance receptors with well-established functions in the nervous system;
      however, their role in the mammalian vasculature remains ill defined. Here we
      show that an endothelial-specific Robo, Robo4, maintains vascular integrity.
      Activation of Robo4 by Slit2 inhibits vascular endothelial growth factor (VEGF)
      165-induced migration, tube formation and permeability in vitro and VEGF-165
      stimulated vascular leak in vivo by blocking Src family kinase activation. In
      mouse models of retinal and choroidal vascular disease, Slit2 inhibited
      angiogenesis and vascular leak, whereas deletion of Robo4 enhanced these
      pathologic processes. Our results define a previously unknown function for Robo
      receptors in stabilizing the vasculature and suggest that activating Robo4 may
      have broad therapeutic application in diseases characterized by excessive
      angiogenesis and/or vascular leak.

PMID- 18345010
TI  - Identification of oxadiazoles as new drug leads for the control of
      schistosomiasis.
AB  - Treatment for schistosomiasis, which is responsible for more than 280,000 deaths
      annually, depends almost exclusively on praziquantel. Millions of people are
      treated annually with praziquantel, and drug-resistant parasites thus are likely
      to evolve. Phosphinic amides and oxadiazole 2-oxides, identified from a
      quantitative high-throughput screen, were shown to inhibit a parasite enzyme,
      thioredoxin glutathione reductase (TGR), with activities in the low micromolar to
      low nanomolar range. Incubation of parasites with these compounds led to rapid
      inhibition of TGR activity and parasite death. The activity of the oxadiazole 2
      oxides was associated with a donation of nitric oxide. Treatment of schistosome
      infected mice with 4-phenyl-1,2,5-oxadiazole-3-carbonitrile-2-oxide led to marked
      reductions in worm burdens from treatments against multiple parasite stages and
      egg-associated pathologies. The compound was active against the three major
      schistosome species infecting humans. These protective effects exceed benchmark
      activity criteria set by the World Health Organization for lead compound
      development for schistosomiasis.

PMID- 18345011
TI  - Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis
      attenuates muscular dystrophy.
AB  - Muscular dystrophies comprise a diverse group of genetic disorders that lead to
      muscle wasting and, in many instances, premature death. Many mutations that cause
      muscular dystrophy compromise the support network that connects myofilament
      proteins within the cell to the basal lamina outside the cell, rendering the
      sarcolemma more permeable or leaky. Here we show that deletion of the gene
      encoding cyclophilin D (Ppif) rendered mitochondria largely insensitive to the
      calcium overload-induced swelling associated with a defective sarcolemma, thus
      reducing myofiber necrosis in two distinct models of muscular dystrophy. Mice
      lacking delta-sarcoglycan (Scgd(-/-) mice) showed markedly less dystrophic
      disease in both skeletal muscle and heart in the absence of Ppif. Moreover, the
      premature lethality associated with deletion of Lama2, encoding the alpha-2 chain
      of laminin-2, was rescued, as were other indices of dystrophic disease. Treatment
      with the cyclophilin inhibitor Debio-025 similarly reduced mitochondrial swelling
      and necrotic disease manifestations in mdx mice, a model of Duchenne muscular
      dystrophy, and in Scgd(-/-) mice. Thus, mitochondrial-dependent necrosis
      represents a prominent disease mechanism in muscular dystrophy, suggesting that
      inhibition of cyclophilin D could provide a new pharmacologic treatment strategy
      for these diseases.

PMID- 18345012
TI  - Interferon-gamma is a therapeutic target molecule for prevention of postoperative
      adhesion formation.
AB  - Intestinal adhesions are bands of fibrous tissue that connect the loops of the
      intestine to each other, to other abdominal organs or to the abdominal wall.
      Fibrous tissue formation is regulated by the balance between plasminogen
      activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (tPA),
      which reciprocally regulate fibrin deposition. Several components of the
      inflammatory system, including cytokines, chemokines, cell adhesion molecules and
      neuropeptide substance P, have been reported to participate in adhesion
      formation. We have used cecal cauterization to develop a unique experimental
      mouse model of intestinal adhesion. Mice developed severe intestinal adhesion
      after this treatment. Adhesion development depended upon the interferon-gamma
      (IFN-gamma) and signal transducer and activator of transcription-1 (STAT1)
      system. Natural killer T (NKT) cell-deficient mice developed adhesion poorly,
      whereas they developed severe adhesion after reconstitution with NKT cells from
      wild-type mice, suggesting that NKT cell IFN-gamma production is indispensable
      for adhesion formation. This response does not depend on STAT4, STAT6,
      interleukin-12 (IL-12), IL-18, tumor necrosis factor-alpha, Toll-like receptor 4
      or myeloid differentiation factor-88-mediated signals. Wild-type mice increased
      the ratio of PAI-1 to tPA after cecal cauterization, whereas Ifng(-/-) or Stat1(
      /-) mice did not, suggesting that IFN-gamma has a crucial role in the
      differential regulation of PAI-1 and tPA. Additionally, hepatocyte growth factor,
      a potent mitogenic factor for hepatocytes, strongly inhibited intestinal adhesion
      by diminishing IFN-gamma production, providing a potential new way to prevent
      postoperative adhesions.

PMID- 18345013
TI  - Detection of colonic dysplasia in vivo using a targeted heptapeptide and confocal
      microendoscopy.
AB  - A combination of targeted probes and new imaging technologies provides a powerful
      set of tools with the potential to improve the early detection of cancer. To
      develop a probe for detecting colon cancer, we screened phage display peptide
      libraries against fresh human colonic adenomas for high-affinity ligands with
      preferential binding to premalignant tissue. We identified a specific
      heptapeptide sequence, VRPMPLQ, which we synthesized, conjugated with fluorescein
      and tested in patients undergoing colonoscopy. We imaged topically administered
      peptide using a fluorescence confocal microendoscope delivered through the
      instrument channel of a standard colonoscope. In vivo images were acquired at 12
      frames per second with 50-microm working distance and 2.5-microm (transverse) and
      20-microm (axial) resolution. The fluorescein-conjugated peptide bound more
      strongly to dysplastic colonocytes than to adjacent normal cells with 81%
      sensitivity and 82% specificity. This methodology represents a promising
      diagnostic imaging approach for the early detection of colorectal cancer and
      potentially of other epithelial malignancies.

PMID- 18345014
TI  - Roles of the Clr4 methyltransferase complex in nucleation, spreading and
      maintenance of heterochromatin.
AB  - Heterochromatin assembly, involving methylation of histone H3 lysine 9 (H3K9me),
      regulates various chromosomal processes. In fission yeast, heterochromatin
      targeted to specific repeat loci in an RNAi-dependent manner spreads across
      extended domains to exert regional epigenetic control. The Clr4 methyltransferase
      complex (ClrC) is responsible for nucleation and spreading of heterochromatin;
      however, its recruitment to heterochromatic repeats is poorly understood. Here we
      demonstrate that ClrC components are distributed throughout heterochromatic
      domains. To nucleate heterochromatin, Rik1, a WD domain-containing subunit of
      ClrC, is loaded onto the transcribed repeats via RNAi machinery including the RNA
      induced transcriptional silencing (RITS) complex. Furthermore, we show that the
      chromodomain of Clr4 binds specifically to H3K9me that is essential for the
      spreading of heterochromatin. Our analyses delineate sequential steps for the
      assembly of heterochromatic domains and suggest that the ability of Clr4 to both
      'write' and 'read' H3K9me facilitates heterochromatin maintenance through
      successive cell divisions.

PMID- 18345015
TI  - GW182 interaction with Argonaute is essential for miRNA-mediated translational
      repression and mRNA decay.
AB  - MicroRNAs (miRNAs) silence gene expression by binding 3' untranslated regions of
      target mRNAs. Recent studies suggested silencing is achieved through either
      recruitment of eIF6, which prevents ribosome assembly, or displacement of eIF4E
      from the mRNA 5' cap structure. Using Drosophila melanogaster cells, we show that
      eIF6 is not required for silencing. In contrast, silencing is abolished by
      mutating Argonaute 1 (AGO1) at two conserved phenylalanine residues predicted to
      mediate binding to the cap structure. Notably, we found these mutations also
      prevented AGO1 from interacting with GW182 and miRNAs, indicating that the
      essential role of these residues is unrelated to cap binding. Consistently,
      depleting GW182 or overexpressing its AGO1 binding domain relieved silencing of
      all reporters tested, including those lacking a poly(A) tail. Together, our
      findings show that miRNA function is effected by AGO1-GW182 complexes and the
      role of GW182 in silencing goes beyond promoting deadenylation.

PMID- 18345016
TI  - Reciprocal regulation of the Ca2+ and H+ sensitivity in the SLO1 BK channel
      conferred by the RCK1 domain.
AB  - Increasing evidence suggests that intracellular H+ directly stimulates large
      conductance Ca2+- and voltage-activated K+ (SLO1 BK) channels, thus providing a
      crucial link between membrane excitability and cell metabolism. Here we report
      that two histidine residues, His365 and His394, located in the intracellular
      regulator of conductance for K+ (RCK) 1 domain, serve as the H+ sensors of the
      SLO1 BK channel. Activation of the channel by H+ requires electrostatic
      interactions between the histidine residues and a nearby negatively charged
      residue involved in the channel's high-affinity Ca2+ sensitivity. Reciprocally,
      His365 and His394 also participate in the Ca2+-dependent activation of the
      channel, functioning as Ca2+ mimetics once they are protonated. Therefore, a
      common motif in the RCK1 domain mediates the stimulatory effects of both H+ and
      Ca2+, and provides a basis for the bidirectional coupling of cell metabolism and
      membrane electrical excitability.

PMID- 18345017
TI  - Hypoxia-inducible factor: roles in development, physiology, and disease.

PMID- 18345020
TI  - Different proteins and biopeptides differently affect satiety and
      anorexigenic/orexigenic hormones in healthy humans.
AB  - OBJECTIVE: We investigated the effects of whey protein (WP), pea protein
      hydrolysate (PPH), a combination of WP+PPH and control (milk protein (MP) which
      consists of 80% casein and 20% WP) on appetite ratings, postprandial changes in
      hunger/satiety hormones and energy intake (EI). DESIGN: A randomized, crossover
      design which consisted of 2 parts (experiment 1 and 2). The peptides to be tested
      were provided as part of a shake (1024 kJ; en% P/F/C: 25/33/42) which contained
      either 15 g WP, 15 g PPH, a combination of 7.5 g WP and 7.5 g PPH (WP+PPH) or 15
      g MP. SUBJECTS: 39 subjects (BMI: 27.6+/-1.7 kg m(-2); age: 42.3+/-13.8 years).
      MEASUREMENTS: In experiment 1 (duration 4 h), appetite profile was measured and
      blood samples were taken for analysis of hunger/satiety hormones and glucose. In
      experiment 2 (duration 7 h), appetite profile and EI (180 min after consumption
      of the shake) were measured. RESULTS: Some indications of lower hunger
      (experiment 1), desire to eat (experiment 2) and thirst (experiment 1 and 2) were
      shown after consumption of PPH compared to MP or WP+PPH (P<0.05). A longer
      intermeal interval and a higher satiety index were suggested after consumption of
      PPH. Both PPH and WP lead to greater satiety (experiment 2) and fullness
      (experiment 2) compared to MP and WP+PPH (P<0.05). For WP, a positive correlation
      between insulin and both cholecystokinine (CCK) and glucagon like peptide-1 (GLP
      1) was observed (P<0.05). However, both CCK and GLP-1 were increased by MP
      (P<0.05), peptide YY (PYY) was stimulated by WP+PPH, while the decline in ghrelin
      was larger (P<0.05). No effect on EI was seen. CONCLUSION: There was modest
      evidence with respect to satiety by PPH consumption. Different exogenous
      biopeptides produced differences in release of endogenous peptides that had
      inconsistent relationships with satiety. Therefore, evidence derived from a
      supposed biomarker for satiety does not guarantee the highest satiety.

PMID- 18345021
TI  - Mucosal delivery of therapeutic and prophylactic molecules using lactic acid
      bacteria.
AB  - Studies of lactic acid bacteria (LAB) as delivery vehicles have focused mainly on
      the development of mucosal vaccines, with much effort being devoted to the
      generation of genetic tools for antigen expression in different bacterial
      locations. Subsequently, interleukins have been co-expressed with antigens in LAB
      to enhance the immune response that is raised against the antigen. LAB have also
      been used as a delivery system for a range of molecules that have different
      applications, including anti-infectives, therapies for allergic diseases and
      therapies for gastrointestinal diseases. Now that the first human trial with a
      Lactococcus strain that expresses recombinant interleukin-10 has been completed,
      we discuss what we have learnt, what we do not yet understand and what the future
      holds for therapy and prophylaxis with LAB.

PMID- 18345023
TI  - Lipoic acid supplementation and endothelial function.
AB  - Endothelial dysfunction is caused by all the recognized cardiovascular risk
      factors and has been implicated in the complex processes leading to the
      initiation and progression of atherosclerosis. Short-term treatment with lipoic
      acid is shown in the current issue of the British Journal of Pharmacology to
      improve endothelial function of aortic rings of old rats. The age-related
      decrease in phosphorylation of nitric oxide synthase and Akt was improved by
      lipoic acid supplementation. The improved phosphorylation status may have been
      due to reduced activity of the phosphatase PPA2, associated with decreased levels
      of endothelial ceramide induced by lipoic acid. Neutral sphingomyelinase activity
      was also reduced by lipoic acid, which was due, at least in part, to increased
      glutathione levels in endothelial cells. The favourable antioxidant, anti
      inflammatory, metabolic and endothelial effects of lipoic acid shown in rodents,
      in this and other recently published studies, warrant further assessment of its
      potential role for prevention and treatment of cardiovascular diseases.

PMID- 18345022
TI  - Neuroplasticity in the mesolimbic dopamine system and cocaine addiction.
AB  - The main characteristics of cocaine addiction are compulsive drug use despite
      adverse consequences and high rates of relapse during periods of abstinence. A
      current popular hypothesis is that compulsive cocaine use and cocaine relapse is
      due to drug-induced neuroadaptations in reward-related learning and memory
      processes, which cause hypersensitivity to cocaine-associated cues, impulsive
      decision making and abnormal habit-like learned behaviours that are insensitive
      to adverse consequences. Here, we review results from studies on the effect of
      cocaine exposure on selected signalling cascades, growth factors and
      physiological processes previously implicated in neuroplasticity underlying
      normal learning and memory. These include the extracellular signal-regulated
      kinase (ERK) signalling pathway, brain-derived neurotrophic factor (BDNF),
      glutamate transmission, and synaptic plasticity (primarily in the form of long
      term potentiation and depression, LTP and LTD). We also discuss the degree to
      which these cocaine-induced neuroplasticity changes in the mesolimbic dopamine
      system mediate cocaine psychomotor sensitization and cocaine-seeking behaviours,
      as assessed in animal models of drug addiction. Finally, we speculate on how
      these factors may interact to initiate and sustain cocaine psychomotor
      sensitization and cocaine seeking.

PMID- 18345024
TI  - Acetazolamide prevents vacuolar myopathy in skeletal muscle of K(+) -depleted
      rats.
AB  - BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase
      (CA) inhibitors effective in the clinical condition of hypokalemic periodic
      paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a
      pathogenic factor in hypoPP, is unknown. The effects of these drugs on the efflux
      of lactate from skeletal muscle were also investigated. EXPERIMENTAL APPROACH:
      For 10 days, K(+)-depleted rats, a model of hypoPP, were administered 5.6 mg kg(
      1) day(-1) of acetazolamide, dichlorphenamide or bendroflumethiazide (the last is
      not an inhibitor of CA). Histological analysis of vacuolar myopathy and in vitro
      lactate efflux measurements were performed in skeletal muscles from treated and
      untreated K(+)-depleted rats, and also from normokalemic rats. KEY RESULTS: About
      three times as many vacuoles were found in the type II fibres of tibialis
      anterioris muscle sections from K(+)-depleted rats as were found in the same
      muscle from normokalemic rats. In ex vivo experiments, a higher efflux of lactate
      on in vitro incubation was found in muscles of K(+)-depleted rats compared with
      that found in muscles from normokalemic rats. After treatment of K(+)-depleted
      rats with acetazolamide, the numbers of vacuoles in tibialis anterioris muscle
      decreased to near normal values. Incubation with acetazolamide in vitro inhibited
      efflux of lactate from muscles of K(+)-depleted rats. In contrast,
      bendroflumethiazide and dichlorphenamide failed to prevent vacuolar myopathy
      after treatment in vivo and failed to inhibit lactate efflux in vitro.
      CONCLUSIONS AND IMPLICATIONS: Acetazolamide prevents vacuolar myopathy in K(+)
      depleted rats. This effect was associated with inhibition of lactate transport,
      rather than inhibition of CA.

PMID- 18345025
TI  - Transgenic expression of the forkhead box M1 transcription factor induces
      formation of lung tumors.
AB  - The forkhead box m1 (Foxm1 or Foxm1b) protein (previously called HFH-11B,
      Trident, Win or MPP2) is abundantly expressed in human non-small cell lung
      cancers where it transcriptionally induces expression of genes essential for
      proliferation of tumor cells. In this study, we used Rosa26-Foxm1 transgenic
      mice, in which the Rosa26 promoter drives ubiquitous expression of Foxm1
      transgene, to identify new signaling pathways regulated by Foxm1. Lung tumors
      were induced in Rosa26-Foxm1 mice using the 3-methylcholanthrene (MCA)/butylated
      hydroxytoluene (BHT) lung tumor initiation/promotion protocol. Tumors from
      MCA/BHT-treated Rosa26-Foxm1 mice displayed a significant increase in the number,
      size and DNA replication compared to wild-type mice. Elevated tumor formation in
      Rosa26-Foxm1 transgenic lungs was associated with persistent pulmonary
      inflammation, macrophage infiltration and increased expression of cyclooxygenase
      2 (Cox-2), Cdc25C phosphatase, cyclin E2, chemokine ligands CXCL5, CXCL1 and
      CCL3, cathepsins and matrix metalloprotease-12. Cell culture experiments with
      A549 human lung adenocarcinoma cells demonstrated that depletion of Foxm1 by
      either short interfering RNA transfection or treatment with Foxm1-inhibiting ARF
      26-44 peptide significantly reduced Cox-2 expression. In co-transfection
      experiments, Foxm1 protein-induced Cox-2 promoter activity and directly bound to
      the -2566/-2580 bp region of human Cox-2 promoter.

PMID- 18345026
TI  - Reduced tumour cell proliferation and delayed development of high-grade mammary
      carcinomas in cathepsin B-deficient mice.
AB  - Expression levels of the papain-like cysteine protease cathepsin B (Ctsb) have
      been positively correlated with mammary tumour progression and metastasis;
      however, its roles in the hallmark processes of malignant growth remain poorly
      defined. Using Ctsb-deficient mice we investigated tumour cell differentiation,
      proliferation and apoptosis in the Tg(MMTV-PyMT) mouse mammary cancer model.
      Absence of Ctsb significantly impaired development of high-grade invasive ductal
      carcinomas and reduced the metastatic burden in the lungs. Mice lacking Ctsb
      exhibited reduced cell proliferation in mammary carcinomas and their lung
      metastases. Notably, intravenous injection of primarily isolated, Ctsb-expressing
      tumour cells into congenic Ctsb-deficient mice revealed impaired cell
      proliferation in the resulting experimental lung metastases, providing evidence
      for the involvement of Ctsb in paracrine regulation of cancer cell proliferation.
      No Ctsb genotype-dependent difference in tumour cell death was observed in vivo
      or by treatment of isolated PyMT cancer cells with tumour necrosis factor-alpha.
      However, cancer cells lacking Ctsb exhibited significantly higher resistance to
      apoptosis induction by the lysosomotropic agent Leu-Leu-OMe. Thus, our results
      indicate an in vivo role for Ctsb in promoting cellular anaplasia in mammary
      cancers and proliferation in lung metastases.

PMID- 18345027
TI  - Human mismatch repair gene, MLH1, is transcriptionally repressed by the hypoxia
      inducible transcription factors, DEC1 and DEC2.
AB  - Tumor hypoxia has been reported to cause a functional loss in DNA mismatch repair
      (MMR) system as a result of downregulation of MMR genes, although the precise
      molecular mechanisms remain unclear. In this study, we focused on the
      downregulation of a key MMR gene, MLH1, and demonstrated that hypoxia-inducible
      transcription repressors, differentiated embryo chondrocytes (DEC1 and 2),
      participated in its transcriptional regulation via their bindings to E-box-like
      motif(s) in MLH1 promoter region. In all cancer cell lines examined, hypoxia
      increased expression of DEC1 and 2, known as hypoxia-inducible genes, but
      decreased MLH1 expression in an exposure time-dependent manner at both the mRNA
      and protein levels. Co-transfection reporter assay revealed that DEC1 and, to
      greater extent, DEC2 as well as hypoxia-repressed MLH1 promoter activity. We
      further found that the action was remarkably inhibited by trichostatin A, and
      identified a possible DEC-response element in the MLH1 promoter. In vitro
      electrophoretic gel mobility shift and chromatin immunoprecipitation assays
      demonstrated that DEC1 or 2 directly bounds to the suggested element, and
      transient transfection assay revealed that overexpression of DEC2 repressed
      endogenous MLH1 expression in the cells. Hypoxia-induced DEC may impair MMR
      function through repression of MLH1 expression, possibly via the histone
      deacethylase-mediated mechanism in cancer cells.

PMID- 18345028
TI  - Axl promotes cell invasion by inducing MMP-9 activity through activation of NF
      kappaB and Brg-1.
AB  - Activity of the Axl receptor tyrosine kinase is positively correlated with tumor
      metastasis; however, its detailed role in the mechanism of tumor invasion is
      still not completely understood. Here, we show that Axl enhances the expression
      of matrix metalloproteinase 9 (MMP-9), required for Axl-mediated invasion both in
      vitro and in vivo. We found that the highly selective MEK1/2 inhibitors U0126 and
      PD98059, and the expressed dominant-negative form of extracellular signal
      regulated kinase (ERK), completely block Axl-mediated MMP-9 activation. In
      contrast, the phosphatidylinositol 3-kinase inhibitor LY294002 and wortmannin had
      little effect on activation. Interestingly, however, the Axl ligand Gas6 is not
      involved in Axl-mediated MMP-9 activation. Mutation of Glu59(Axl) and Thr77(Axl)
      dramatically reduced Gas6-Axl binding but continued to induce MMP-9 activation.
      In addition, overexpression of Axl-activated ERK and enhanced nuclear factor
      kappaB (NF-kappaB) transactivation and brahma-related gene-1 (Brg-1)
      translocation. Exposure to the NF-kappaB inhibitor silibinin, which inhibits
      IkappaBalpha kinase activity, or overexpression of the dominant-negative mutant
      IkappaB and Brg-1 strikingly inhibited Axl-mediated MMP-9 activation. These data
      indicate that coordination of ERK signaling and NF-kappaB and Brg-1 activation
      are indispensable to regulation of Axl-dependent MMP-9 gene transcription.
      Together with previous data, our results provide a plausible mechanism for Axl
      mediated tumor invasion and establish a functional link between the Axl and MMP-9
      signaling pathways.

PMID- 18345029
TI  - Co-injection strategies to modify radiation sensitivity and tumor initiation in
      transgenic Zebrafish.
AB  - The zebrafish has emerged as a powerful genetic model of cancer, but has been
      limited by the use of stable transgenic approaches to induce disease. Here, a co
      injection strategy is described that capitalizes on both the numbers of embryos
      that can be microinjected and the ability of transgenes to segregate together and
      exert synergistic effects in forming tumors. Using this mosaic transgenic
      approach, gene pathways involved in tumor initiation and radiation sensitivity
      have been identified.

PMID- 18345030
TI  - A role for Myc in facilitating transcription activation by E2F1.
AB  - Previous work has demonstrated that E2F proteins regulate the expression of
      various genes encoding proteins essential for DNA replication and cell-cycle
      progression. E2F1 in particular is required for the initial entry to the cell
      cycle from a quiescent state and is required for the activation of other E2F
      genes. Other work has demonstrated a role for the Myc transcription factor in the
      activation of a large number of genes associated with cell growth, including E2F
      genes. We now show that Myc is required to allow the interaction of the E2F1
      protein with the E2F gene promoters. As such, Myc thus provides a link between
      the development of a growth-competent state during the initial stage of G(1) and
      the activation of genes essential for DNA replication at G(1)/S.

PMID- 18345031
TI  - NSC348884, a nucleophosmin inhibitor disrupts oligomer formation and induces
      apoptosis in human cancer cells.
AB  - Nucleophosmin (NPM), a multifunctional nucleolar phosphoprotein is dysregulated
      in human malignancies leading to anti-apoptosis and inhibition of
      differentiation. We evaluated the precise three-dimensional structure of NPM
      based on the highly conserved structure of Xenopus NO38 and its requirement to
      form dimers and pentamers via its N-terminal domain (residues, 1-107). We
      hypothesized that a small molecular inhibitor (SMI) that could disrupt the
      formation of dimers would inhibit aberrant NPM function(s) in cancer cells.
      Molecular modeling, pharmacophore design, in silico screening and interactive
      docking identified NSC348884 as a putative NPM SMI that disrupts a defined
      hydrophobic pocket required for oligomerization. NSC348884 inhibited cell
      proliferation at an IC(50) of 1.7-4.0 muM in distinct cancer cell lines and
      disrupted NPM oligomer formation by native polyacrylamide gel electrophoresis
      assay. Treatment of several different cancer cell types with NSC348884
      upregulated p53 (increased Ser15 phosphorylation) and induced apoptosis in a dose
      dependent manner that correlated with apoptotic markers: H2AX phosphorylation,
      poly(ADP-ribose) polymerase cleavage and Annexin V labeling. Further, NSC348884
      synergized doxorubicin cytotoxicity on cancer cell viability. The data together
      show that NSC348884 is an SMI of NPM oligomer formation, upregulates p53, induces
      apoptosis and synergizes with chemotherapy. Hence, an SMI to NPM may be a useful
      approach to anticancer therapy.

PMID- 18345032
TI  - Oncolytic herpes virus with defective ICP6 specifically replicates in quiescent
      cells with homozygous genetic mutations in p16.
AB  - Oncolytic herpes simplex viruses (HSVs), in clinical trials for the treatment of
      malignant gliomas, are assumed to be selective for tumor cells because their
      replication is strongly attenuated in quiescent cells, but not in cycling cells.
      Oncolytic selectivity is thought to occur because mutations in viral ICP6
      (encoding a viral ribonucleotide reductase function) and/or gamma34.5 function
      are respectively complemented by mammalian ribonucleotide reductase and GADD34,
      whose genes are expressed in cycling cells. However, it is estimated that only 5
      15% of malignant glioma cells are in mitosis at any one time. Therefore,
      effective replication of HSV oncolytic viruses might be limited to a
      subpopulation of tumor cells, since at any one time the majority of tumor cells
      would not be cycling. However, we report that an HSV with defective ICP6 function
      replicates in quiescent cultured murine embryonic fibroblasts obtained from mice
      with homozygous p16 deletions. Furthermore, intracranial inoculation of this
      virus into the brains of p16-/- mice provides evidence of viral replication that
      does not occur when the virus is injected into the brains of wild-type mice.
      These approaches provide in vitro and in vivo evidence that ICP6-negative HSVs
      are 'molecularly targeted,' because they replicate in quiescent tumor cells
      carrying specific oncogene deletions, independent of cell cycle status.

PMID- 18345033
TI  - P53-mediated upregulation of DcR1 impairs oxaliplatin/TRAIL-induced synergistic
      anti-tumour potential in colon cancer cells.
AB  - Oxaliplatin has emerged as a major chemotherapeutic drug in the treatment of
      advanced colorectal cancer, yet like most conventional cancer therapeutics, its
      efficacy is often compromised due to p53 mutations. Unlike oxaliplatin, tumour
      necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis in a
      p53-independent manner, and chemotherapy is known to overcome tumour resistance
      to TRAIL-induced cell death in most cancer cells. Using a panel of colon cancer
      cell lines, we assessed the ability of oxaliplatin to sensitize to TRAIL-induced
      apoptosis. We demonstrate that while both drugs additively or synergistically
      induced apoptosis in almost all cell lines tested, p53 wild-type colon cancer
      cells such as HCT116, LS513 or LS174T remained resistant. Impaired TRAIL-induced
      cell death resulted from a strong p53 dependent, oxaliplatin-mediated, DcR1
      receptor expression increase. According to our finding, downregulation of DcR1
      using siRNA, in p53 wild-type colon cancer cells, restored oxaliplatin/TRAIL
      synergistic apoptotic activity. On the contrary, exogenous DcR1 overexpression in
      SW480, a p53-mutated cell line, abolished the synergy between the two drugs.
      Altogether we demonstrate for the first time that p53 negatively regulates
      oxaliplatin-mediated TRAIL-induced apoptotic activity through DcR1 upregulation.
      Our findings could have important implications for future therapeutic strategies,
      and suggest that the association oxaliplatin/TRAIL should be restricted to
      patients harbouring a non-functional p53 protein.

PMID- 18345034
TI  - Expression of the BRCA1-interacting protein Brip1/BACH1/FANCJ is driven by E2F
      and correlates with human breast cancer malignancy.
AB  - Mutations in the BRCA1-interacting DEAH helicase Brip1 confer an increased risk
      of breast cancer. In the present study we aimed to unravel the transcriptional
      control of Brip1 and to determine its expression levels in a set of 101 primary
      invasive breast carcinomas. Transcription of Brip1 was found to be cell growth
      related and controlled by the E2F/retinoblastoma (Rb) pathway through a conserved
      E2F-responsive site. Repression of Brip1 expression by the cell growth-inhibiting
      compound 1alpha,25-dihydroxyvitamin D3 depended on this same E2F-responsive site.
      In spite of its role as a tumor suppressor, both quantitative reverse
      transcriptase-PCR analyses and immunohistochemical stainings showed significantly
      elevated Brip1 expression levels in grade 3 tumors as compared to grade 1 or 2
      carcinomas. Furthermore, increased Brip1 transcript levels were found in tumors
      with an estrogen receptor-negative, progesterone receptor-negative or HER-2
      positive status. In conclusion, these data show that Brip1 is a genuine target
      gene for the E2F/Rb pathway and that elevated expression levels of Brip1 are
      detected in primary invasive breast carcinomas with unfavorable characteristics.

PMID- 18345035
TI  - Targeted disruption of Aurora A causes abnormal mitotic spindle assembly,
      chromosome misalignment and embryonic lethality.
AB  - Aurora A (also known as STK15/BTAK in humans), a putative oncoprotein naturally
      overexpressed in many human cancers, is a member of the conserved Aurora protein
      serine/threonine kinase family that is implicated in the regulation of G(2)-M
      phases of the cell cycle. In vitro studies utilizing antibody microinjection,
      siRNA silencing and small molecule inhibitors have indicated that Aurora A
      functions in early as well as late stages of mitosis. However, due to limitations
      in specificity of the techniques, exact functional roles of the kinase remain to
      be clearly elucidated. In order to identify the physiological functions in vivo,
      we have generated Aurora A null mouse embryos, which show severe defects at 3.5
      d.p.c. (days post-coitus) morula/blastocyst stage and lethality before 8.5 d.p.c.
      Null embryos at 3.5 d.p.c. reveal growth retardation with cells in mitotic
      disarray manifesting disorganized spindle, misaligned and lagging chromosomes as
      well as micronucleated cells. These findings provide the first unequivocal
      genetic evidence for an essential physiological role of Aurora A in normal
      mitotic spindle assembly, chromosome alignment segregation and maintenance of
      viability in mammalian embryos.

PMID- 18345036
TI  - Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors
      following actin damage.
AB  - We previously reported that actin damage by treatment with an actin
      depolymerizing agent including pectenotoxin-2 induces Bim-mediated apoptosis in
      p53-deficient human tumors. In this study, we investigated a molecular mechanism
      underlying Bim-mediated apoptosis of p53-deficient tumor cells following actin
      damage. We found that actin inhibitors increased the protein levels of p53 and
      p21 and thereby inactivated both Cdk2 and Cdc2 kinases. However, p53- or p21
      knockout cells fail to induce p21 and hence kept both Cdk2 and Cdc2 kinases
      active even after treatment with actin inhibitor. The p53- or p21-knockout cells
      became multinucleate and polyploidy in association with induction of apoptosis.
      Expression of Bcl-x(L) resulted in accumulation of polyploid cells in association
      with inhibition of apoptosis. However, expression of a dominant negative mutant
      (Cdk2dn) and treatment with chemical inhibitors for Cdk2 suppressed not only
      accumulation of multinucleated cells, but also induction of Bim expression and
      apoptosis. Therefore, these results suggest that Bim-mediated apoptosis following
      actin damage due to deregulation of Cdk2 and the cell cycle by the absence of
      functional p53.

PMID- 18345037
TI  - Low sideband guided-mode resonant filter.
AB  - A guided-mode resonant filter with low sideband reflections is proposed. It is
      shown that, for serious reduction of out-of band reflectance, the combination of
      waveguide-grating filter design with conventional antireflective stack design
      methods is not adequate. To achieve symmetrical low sideband reflectances,
      independent control of various layer thicknesses is necessary. At a given
      illumination angle with appropriate control of the waveguide thickness, a
      specific resonant grating filter is designed whose out-of-band reflectance on
      both sides of the resonant peak is well below 10(-4). Even 50 nm away from the
      peak, on both sides, the out-of-band reflectance remains below 10(-3). Analysis
      of the variation in the main manufacturing parameters indicates that such filters
      can be reliably produced with present-day technologies.

PMID- 18345038
TI  - Design for an aberration-corrected concave grating for a mid-infrared long-slit
      spectrometer.
AB  - A new design for an aberration-corrected concave grating for the spectral region
      near 10 microm is presented. It was designed for use in the ground-based
      astronomical medium-resolution (lambda/Dlambda approximately 100) Mid-Infrared
      Camera and Spectrometer (MICS). It provides a flat focal plane for a wide
      spectral range (7.5-13.5 microm) with small aberrations, permitting efficient
      long-slit observations in the mid-infrared region. It permits a simple design of
      the spectrometer without collimator and camera mirrors, which is quite
      advantageous for cryogenic instruments. The grating has variable spacing grooves
      to reduce aberrations. In addition, the grating surface figure is designed to be
      toroidal and in the direction perpendicular to the grooves, aspherical, to
      suppress the aberrations further over a wide spectral range. The angle of the
      grooves is also varied to yield better efficiency near the blaze angle. The
      grating was fabricated by high-quality ultraprecision machining, which made these
      features possible. Test observations confirmed that the designed spectral
      resolution was achieved.

PMID- 18345039
TI  - Speckle imaging and hidden phase.
AB  - The Knox-Thompson, or cross-spectrum, method provides two two-dimensional
      difference equations for the phase of the object spectrum. We demonstrate that,
      in general, the object spectrum phase can be decomposed into a regular, single
      valued function determined by the divergence of the phase gradient, as well as a
      multivalued function determined by the circulation of the phase gradient; this
      second function has been called the hidden phase. The standard least-squares
      solution to the two-dimensional difference equations will always miss this hidden
      phase. We present a solution method that gives both the regular and the hidden
      parts of the object spectrum phase. Finally, we illustrate several examples of
      imaging through turbulence and postprocessing with the Knox-Thompson method,
      including the hidden phase.

PMID- 18345040
TI  - Fabrication of thin-film micropolarizer arrays for visible imaging polarimetry.
AB  - We describe a microfabrication process for fabricating micropolarizer devices
      with polarization thin film. The polarization film is less than a 0.5 microm
      thick and can have a polarization extinction ratio of approximately 330 in the
      visible wavelength range. A single-state micropolarizer array with polarizing
      pixels as small as 5 microm x 5 microm has been fabricated. A multilayer
      spatially multiplexed three-state micropolarizer line array with a 14.4-microm
      resolution has also been fabricated for visible imaging polarimetry application.

PMID- 18345041
TI  - Talbot array illuminator for single-shot measurements of laser-induced-damage
      thresholds of thin-film coatings.
AB  - A highly efficient Talbot array illuminator for single-shot, laser-induced-damage
      test measurements of optical thin-film coatings is proposed. With a periodic
      binary phase grating, a laser beam is transformed into an ensemble of Gaussian
      like spots, which are known as the Fresnel image of the grating. For this purpose
      hexagonal phase gratings were fabricated and analyzed. With a peak fluence
      distribution of approximately 1 order of magnitude, the damage threshold of thin
      films can be deduced by use of the data from only a single shot.

PMID- 18345042
TI  - Sampling period criterion in a scanning-beam technique.
AB  - The scanning-beam technique for measuring the response of a detector to an
      irradiance is analyzed. With this method the irradiance responsivity is
      determined by integration of the spatial responsivity. Since in practice the
      integration is approximated by a summation over steps with a finite step size,
      errors are introduced. It is shown both theoretically and experimentally that the
      error vanishes when the reciprocal step size lies beyond the diffraction limit.
      Furthermore, comparison shows that experiment and theory are in good agreement.

PMID- 18345043
TI  - Coherent detection in Doppler global velocimetry: a simplified method to measure
      subsonic fluid flow fields.
AB  - The principles of an entirely new method to demodulate Doppler signals in Doppler
      global velocimetry (DGV) are discussed. The method makes use of coherent
      detection and streak imaging to record both temporal and spatial information on a
      single image. The method retains the simplicity of the basic DGV technique yet
      increases its applicability to subsonic flow regimes. The combination of a
      straightforward optical configuration and the ability to collect large data sets
      efficiently make this technique particularly useful in high-cost experimental
      facilities such as wind-tunnel testing where large quantities of data must be
      collected in a relatively short time period.

PMID- 18345044
TI  - Position and displacement sensing with shack-hartmann wave-front sensors.
AB  - The use of a Shack-Hartmann wave-front sensor as a position-sensing device is
      proposed and demonstrated. The coordinates of a pointlike object are determined
      from the modal Zernike coefficients of the wave fronts emitted by the object and
      detected by the sensor. The position of the luminous centroid of a moderately
      extended incoherent flat object can also be measured with this device.
      Experimental results with off-the-shelf CCD cameras and conventional relay optics
      as well as inexpensive diffractive microlens arrays show that axial positioning
      accuracies of 74 microm rms at 300 mm and angular accuracies of 4.3 microrad rms
      can easily be achieved.

PMID- 18345045
TI  - High-precision velocimetry: optimization of a fabry-perot interferometer.
AB  - We present the optimization of a Fabry-Perot velocimeter designed to measure
      speed at a few millimeters per second with a relative uncertainty of 10(-8). We
      focus on the accuracy and the optimization of the Fabry-Perot, with a review of
      the uncertainties related to the geometry, the beam shape, and the Doppler
      frequency measurement. These errors are quantified to ensure that the required
      accuracy is reached. We then describe the practical implementation and show the
      results.

PMID- 18345046
TI  - Diffractive grazing-incidence interferometer.
AB  - I propose a symmetric geometry for grazing-incidence interferometry of flat
      surfaces using diffraction gratings for beam splitting and recombination. The
      geometry employs a reference mirror to correct for relative inversion of the
      measurement and reference wave fronts. Preliminary testing with a 4-microm
      equivalent-wavelength system shows a 3 sigma repeatability of 20 nm for both
      smooth and rough surfaces, including a variety of precision-engineered metal,
      ceramic, and glass objects. The system has a comfortable working distance and
      large field of view, suitable for production testing.

PMID- 18345047
TI  - Use of radiation and hybrid modes to increase the accuracy in the determination
      of the refractive indices of rutile.
AB  - A new method to correlate prism and substrate refractive indices is presented and
      applied to the determination of rutile refractive indices, both ordinary and
      extraordinary, at different wavelengths in the visible and the near infrared. The
      method exploits radiation modes and, when the sample structure allows it, hybrid
      modes. An accuracy of approximately 2 x 10(-4) was achieved without the need of
      any specific preparation of the samples. The method exhibits a good versatility
      since it can be exploited for the determination of the refractive index of a
      coupling prism when the substrate index is known and vice versa.

PMID- 18345048
TI  - Optical properties of hot-pressed B4C in the extreme ultraviolet.
AB  - Hot-pressed B(4)C is found to have a high normal reflectance in the extreme-UV
      spectral region above 49 nm. This reflectance is comparable with or higher than
      chemical-vapor-deposited SiC in the spectral region from 49 to 92 nm. Reflectance
      measurements as a function of the angle of incidence yielded the optical
      constants of B(4)C in the spectral range 49-121.6 nm.

PMID- 18345049
TI  - Grinding process for beveling and lapping operations in lens manufacturing.
AB  - A grinding process that uses loose abrasives for the beveling of lenses is
      presented. Determination of the parameters of grinding tools with loose abrasives
      for beveling applications with various optical elements is discussed. The process
      of grinding with loose abrasives for a lapping operation is analyzed by
      examination of the influence of optical glass material parameters on material
      removal and surface roughness for lens manufacturing conditions. The model
      established for this analysis uses the concept of lateral fracture, which is
      based on removal of optical glass material by rolling abrasive particles. The
      particles remove material by lateral cracking. The abrasive mineral Barton Garnet
      was used in the lapping experiments. Under specific large-diameter lens
      manufacturing conditions, lapping time values at the conventional removal depth
      have been obtained for various optical glasses.

PMID- 18345050
TI  - Two-dimensional polarization encoding with a phase-only liquid-crystal spatial
      light modulator.
AB  - We show how to two dimensionally encode the polarization state of an incident
      light beam using a parallel-aligned liquid-crystal spatial light modulator
      (LCSLM). Each pixel of the LCSLM acts as a voltage-controlled wave plate and can
      be programmed over a 2pi phase range at a wavelength of 514.5 nm. Techniques are
      reviewed for either rotating the major axis of elliptically polarized light or
      for converting an input linearly polarized beam into an arbitrary elliptically
      polarized beam. Experimental results are demonstrated in which we generate
      various two-dimensional spatial patterns of polarized light. Several potential
      applications are suggested. We also report an unexpected edge-enhancement effect
      that might be useful in image processing applications.

PMID- 18345051
TI  - Fabrication of hollow waveguides for CO2 lasers.
AB  - Germanium-coated metal (silver, gold, and copper) hollow waveguides for CO(2)
      laser energy delivery have been fabricated by electron-beam evaporation and
      plating techniques in which an acid-soluble glass mandrel with small surface
      roughness was used. The transmission characteristics of Ge-coated metal hollow
      waveguides were studied. Ge-coated Ag hollow waveguides showed smaller loss, 0.2
      dBm, for CO(2) laser light than Ge-coated Au and Cu waveguides. The transmission
      characteristics of Ge-coated Ag hollow waveguides were measured in relation to a
      core diameter and a bending radius.

PMID- 18345052
TI  - Slope distribution of a rough surface measured by transmission scattering and
      polarization.
AB  - Transmission scattering from medium to air was used to measure the slope
      distribution of the rough plane surface of a transparent glass hemisphere. A
      facet model successfully explained the measured results of refraction,
      scattering, and polarization: Transmission scattering existed for incident angles
      greater than the critical angle, all measured curves for the normalized scattered
      intensity versus the facet slope angle for different detection directions
      overlapped, and the measured polarization of scattering was approximately
      constant for >99% of the facets. The slope distribution obtained by transmission
      scattering agrees with those of the surface profiles in the valid range of the
      profiler and can represent the slope distribution of the rough surface.

PMID- 18345053
TI  - Refractive-index and element-spacing effects on the spectral behavior of infrared
      frequency-selective surfaces.
AB  - Transmission and reflection characteristics of inductive-mesh frequency-selective
      surfaces were measured in the 4-12-microm range. Specific issues investigated
      include the effect of interelement spacing on the location and width of the
      resonance and the influence of superstrate and substrate refractive indices on
      the spectral response of the structure.

PMID- 18345054
TI  - Spatial distribution of single-photon and two-photon fluorescence light in
      scattering media: Monte Carlo simulation.
AB  - Three-dimensional fluorescence spatial distributions under single-photon and two
      photon excitation within a turbid medium are studied with Monte Carlo simulation.
      It is demonstrated that two-photon excitation has an advantage of producing much
      less fluorescence light outside the focal region compared with single-photon
      excitation. With the increase of the concentration of scattering particles in a
      turbid medium, the position of the maximum fluorescence intensity point shifts
      from the geometric focal region toward the medium surface. Further studies show
      that the optical sectioning property of two-photon fluorescence microscopy is
      degraded in thick turbid media or when the numerical aperture of an objective
      becomes low.

PMID- 18345055
TI  - Monte Carlo simulations of the diffuse backscattering mueller matrix for highly
      scattering media.
AB  - We have developed a Monte Carlo algorithm that computes all two-dimensional
      elements of the diffuse backscattering Mueller matrix for highly scattering
      media. Using the Stokes-Mueller formalism and scattering amplitudes calculated
      with Mie theory, we are able to consider polarization-dependent photon
      propagation in highly scattering media, including linearly and circularly
      polarized light. The numerically determined matrix elements are compared with
      experimental data for different particle sizes and show good agreement in both
      azimuthal and radial direction.

PMID- 18345056
TI  - Defect formation in hafnium dioxide thin films.
AB  - Hafnium dioxide thin films were deposited by reactive electron-beam evaporation
      at six different substrate temperatures on fused-silica substrates. During the
      depositions, the scattering of light caused by the growth of defects in the films
      was recorded with in situ total internal reflection microscopy. After deposition
      the films were analyzed by angle-resolved scatterometery, spectrophotometric
      measurement of film reflectance and transmittance, atomic force microscopy, and x
      ray diffraction. We explore the effects of film defect formation on film optical
      properties and film surface topography using these data.

PMID- 18345057
TI  - On the etalon effect generated by a Pockels cell with high-quality antireflection
      coatings.
AB  - We discuss the modulation in the spectrum generated by the windows of a Pockels
      cell. Although they are antireflection coated, the residual reflectivity of the
      highly parallel window faces can still have etalon effects that lead to
      pronounced spectrum modulation. This problem is easily solved by the use of
      slightly wedged windows.

PMID- 18345058
TI  - Correction masks for thickness uniformity in large-area thin films.
AB  - Experimental results from the emission of vapor sources are considered in
      designing correcting diaphragms to achieve a uniform thickness distribution
      during evaporation of thin films mounted on large-area substrate holders, in
      different geometric configurations.

PMID- 18345059
TI  - Correlation between optical path modulations and transmittance spectra of a-Si:H
      thin films.
AB  - The optical constants of plasma-enhanced chemical-vapor-deposited amorphous
      silicon (a-Si:H) thin film upon a transparent substrate are determined within the
      UV-visible region by measurement of the transmittance spectrum. Apart from
      thickness irregularities, the effects of vertical film inhomogeneities
      (refractive-index distribution) on the spectrum are discussed. In this respect,
      although consideration of any possible variation in thickness of the film within
      the area illuminated by the probe beam is sufficient for correcting the
      modulation of the extrema of interference fringes, including in the model the
      thin transitional regions at substrate-film and film-air interfaces might be an
      alternative method for understanding the overall optical behavior of the
      spectrum.

PMID- 18345060
TI  - Mo/Si and Mo/Be multilayer thin films on Zerodur substrates for extreme
      ultraviolet lithography.
AB  - Multilayer-coated Zerodur optics are expected to play a pivotal role in an
      extreme-ultraviolet (EUV) lithography tool. Zerodur is a multiphase,
      multicomponent material that is a much more complicated substrate than commonly
      used single-crystal Si or fused-silica substrates. We investigate the effect of
      Zerodur substrates on the performance of high-EUV reflectance Mo/Si and Mo/Be
      multilayer thin films. For Mo/Si the EUV reflectance had a nearly linear
      dependence on substrate roughness for roughness values of 0.06-0.36 nm rms, and
      the FWHM of the reflectance curves (spectral bandwidth) was essentially constant
      over this range. For Mo/Be the EUV reflectance was observed to decrease more
      steeply than Mo/Si for roughness values greater than approximately 0.2-0.3 nm.
      Little difference was observed in the EUV reflectivity of multilayer thin films
      deposited on different substrates as long as the substrate roughness values were
      similar.

PMID- 18345061
TI  - Relation between coupled-mode theory and equivalent layers for multilayer
      interference coatings.
AB  - The method of equivalent layers is a commonly used technique for designing
      optical multilayer interference coatings. Herpin's theorem [C. R. Acad. Sci. 225,
      182 (1947)] states that every symmetrical multilayer structure is equivalent, at
      one arbitrary wavelength, to a single homogeneous layer. The Herpin equivalent
      layer is described by two design parameters, the equivalent index and the
      equivalent thickness. Alternatively, we recently developed an exact coupled-mode
      analysis for the description of multilayer interference coatings composed of a
      symmetrical combination of layers. The design parameters of the coupled-mode
      theory are the exact coupling coefficient and the exact detuning coefficient.
      Recently we used this method in the design of chirped mirrors for dispersion
      compensation. We prove that the two methods are equivalent and derive relations
      that link the design parameters of both formalisms. By use of these relations it
      is possible to translate between the coupled-mode formalism and the method of
      equivalent layers. The simultaneous availability of both design methods gives a
      new perspective on the analytical design of optical interference coatings with
      challenging spectral response characteristics.

PMID- 18345062
TI  - X-ray interferometry of surfaces with Fresnel mirrors.
AB  - With a small double-mirror setup, we used grazing-x-ray interferometry to study
      nanometric steps. These one-dimensional steps were microfabricated upon the
      surface of one of the two mirrors; the other mirror provided the reference wave.
      Two geometries were studied. In the longitudinal case in which the x rays are
      parallel to the step edges, it is straightforward to determine the step size. In
      the transverse case, one deals with Fourier holography, and a reconstruction
      process for a phase object had been demonstrated for the case of a single step.

PMID- 18345063
TI  - Optimum modulation and demodulation matrices for solar polarimetry.
AB  - Both temporal and/or spatial modulation are mandatory in current solar
      polarimetry [Appl. Opt. 24, 3893 (1985); 26, 3838 (1987)]. The modulating and
      demodulating processes are mathematically described by matrices O and D,
      respectively, on whose structure the accuracy of Stokes parameter measurements
      depend. We demonstrate, based on the definition of polarimetric efficiency
      [Instituto de Astrofisica de Canarias Internal Report (1994); ASP Conf. Ser. 184,
      3 (1999)], that the maximum efficiencies of an ideal polarimeter are unity for
      Stokes I and for (Q(2) + U(2) + V(2))(1/2) and that this occurs if and only if
      O(T)O is diagonal; given a general (possibly nonideal) modulation matrix O, the
      optimum demodulation matrix turns out to be D = (O(T)O)(-1)O(T); and the maximum
      efficiencies in the nonideal case are given by the rms value of the column
      elements of matrix O and are reached by modulation matrices such that O(T)O is
      diagonal. From these analytical results we distill two recipes useful in the
      practical design of polarimeters. Their usefulness is illustrated by discussing
      cases of currently available solar polarimeters. Although specifically devoted to
      solar polarimetry, the results here may be applied in practically all other
      branches of science for which polarimetric measurements are needed.

PMID- 18345064
TI  - Simulation of the effects of atmospheric turbulence on mid-infrared visibility
      measurements with the mid-infrared interferometric instrument for the very large
      telescope interferometer.
AB  - The mid-infrared interferometric instrument is one of three instruments that will
      equip the focus of the Very Large Telescope Interferometer. During the design
      phase of the instrument we made use of a program of simulations to define the
      constraints imposed by atmospheric turbulence. We present our results for the
      estimated fringe motion, during a typical sampling time of 100 ms, and for the
      estimated fringe visibility with and without tip-tilt correction. Our simulations
      were run assuming an outer scale of turbulence of 25 m against an infinite value
      as strictly implied by Kolmogorov statistics. The results show that this has
      positive consequences for our applications, above all as far as fringe motion is
      concerned. We also take into consideration the effect of background noise on the
      accuracy of the fringe visibility measurements and the effect of self-fringe
      tracking, which has been simulated by a linear fringe-tracker algorithm.

PMID- 18345065
TI  - Polarization effects in 4Pi confocal microscopy studied with water-immersion
      lenses.
AB  - We studied the effect of electric field orientation on the point-spread function
      (PSF) of a 4Pi microscope. We show that in a standard 4Pi arrangement the
      orientation of the field can be used for changing between constructive- and
      destructive-mode 4Pi microscopy. The effect is counteracted by introduction of a
      phase shift of pi into one of the half-arms. This compensation is compulsory
      during illumination with unpolarized or circularly polarized light. By performing
      our experiments with 1.2-N.A. water-immersion lenses, we demonstrate that water
      immersion is suitable for 4Pi confocal microscopy. At a two-photon excitation
      wavelength of 1064 nm, the water 4Pi confocal PSF features an axial lobe of 40%
      above and below the focal plane, which, by linear filtering, can be unambiguously
      removed. The measured axial full width at half-maximum of the PSF is 240 nm. This
      is 4.3 times narrower than its single-lens confocal counterpart. The 4Pi confocal
      microscope sets a new resolution benchmark in three-dimensional imaging of watery
      samples.

PMID- 18345066
TI  - Chemometric analysis of frequency-domain photon migration data: quantitative
      measurements of optical properties and chromophore concentrations in
      multicomponent turbid media.
AB  - Frequency-domain photon migration (FDPM) is a widely used technique for measuring
      the optical properties (i.e., absorption, micro(a), and reduced scattering,
      micro(s)', coefficients) of turbid samples. Typically, FDPM data analysis is
      performed with models based on a photon diffusion equation; however, analytical
      solutions are difficult to obtain for many realistic geometries. Here, we
      describe the use of models based instead on representative samples and
      multivariate calibration (chemometrics). FDPM data at seven wavelengths (ranging
      from 674 to 956 nm) and multiple modulation frequencies (ranging from 50 to 600
      MHz) were gathered from turbid samples containing mixtures of three absorbing
      dyes. Values for micro(a) and micro(s)' were extracted from the FDPM data in
      different ways, first with the diffusion theory and then with the chemometric
      technique of partial least squares. Dye concentrations were determined from the
      FDPM data by three methods, first by least-squares fits to the diffusion results
      and then by two chemometric approaches. The accuracy of the chemometric
      predictions was comparable or superior for all three dyes. Our results indicate
      that chemometrics can recover optical properties and dye concentrations from the
      frequency-dependent behavior of photon density waves, without the need for
      diffusion-based models. Future applications to more complicated geometries, lower
      scattering samples, and simpler FDPM instrumentation are discussed.

PMID- 18345068
TI  - Communicating with waves between volumes: evaluating orthogonal spatial channels
      and limits on coupling strengths.
AB  - A rigorous method for finding the best-connected orthogonal communication
      channels, modes, or degrees of freedom for scalar waves between two volumes of
      arbitrary shape and position is derived explicitly without assuming planar
      surfaces or paraxial approximations. The communication channels are the solutions
      of two eigenvalue problems and are identical to the cavity modes of a double
      phase-conjugate resonator. A sum rule for the connection strengths is also
      derived, the sum being a simple volume integral. These results are used to
      analyze rectangular prism volumes, small volumes, thin volumes in different
      relative orientations, and arbitrary near-field volumes: all situations in which
      previous planar approaches have failed for one or more reasons. Previous planar
      results are reproduced explicitly, extending them to finite depth. Depth is shown
      not to increase the number of communications modes unless the volumes are close
      when compared with their depths. How to estimate the connection strengths in some
      cases without a full solution of the eigenvalue problem is discussed so that
      estimates of the number of usable communications modes can be made from the sum
      rule. In general, the approach gives a rigorous basis for handling problems
      related to volume sources and receivers. It may be especially applicable in near
      field problems and in situations in which volume is an intrinsic part of the
      problem.

PMID- 18345069
TI  - Passive ranging through wave-front coding: information and application.
AB  - Passive-ranging systems based on wave-front coding are introduced. These single
      aperture hybrid optical-digital systems are analyzed by use of linear models and
      the Fisher information matrix. Two schemes for passive ranging by use of a single
      aperture and a single image are investigated: (i) estimating the range to an
      object and (ii) detecting objects over a set of ranges. Theoretical limitations
      on estimator-error variances are given by use of the Cramer-Rao bounds.
      Evaluations show that range estimates with less than 0.1% error can be obtained
      from a single wave-front coded image. An experimental system was also built, and
      example results are given.

PMID- 18345070
TI  - Visual communication with retinex coding.
AB  - Visual communication with retinex coding seeks to suppress the spatial variation
      of the irradiance (e.g., shadows) across natural scenes and preserve only the
      spatial detail and the reflectance (or the lightness) of the surface itself. The
      separation of reflectance from irradiance begins with nonlinear retinex coding
      that sharply and clearly enhances edges and preserves their contrast, and it ends
      with a Wiener filter that restores images from this edge and contrast
      information. An approximate small-signal model of image gathering with retinex
      coding is found to consist of the familiar difference-of-Gaussian bandpass filter
      and a locally adaptive automatic-gain control. A linear representation of this
      model is used to develop expressions within the small-signal constraint for the
      information rate and the theoretical minimum data rate of the retinex-coded
      signal and for the maximum-realizable fidelity of the images restored from this
      signal. Extensive computations and simulations demonstrate that predictions based
      on these figures of merit correlate closely with perceptual and measured
      performance. Hence these predictions can serve as a general guide for the design
      of visual communication channels that produce images with a visual quality that
      consistently approaches the best possible sharpness, clarity, and reflectance
      constancy, even for nonuniform irradiances. The suppression of shadows in the
      restored image is found to be constrained inherently more by the sharpness of
      their penumbra than by their depth.

PMID- 18345071
TI  - Information-based optical design for binary-valued imagery.
AB  - Applications such as optical data storage, optical computing, and optical
      interconnects require optical systems that manipulate binary-valued images. Such
      an optical system can be viewed as a two-dimensional array of binary
      communication channels. This perspective is used to motivate the use of pagewise
      mutual information as a metric for optical system analysis and design. Fresnel
      propagation and coherent imaging both are analyzed in terms of mutual-information
      transmission. An information-based space-bandwidth product is used to analyze the
      trade-off between the numerical aperture and the number of image pixels in a
      coherent 4f system. We propose a new merit function to facilitate information
      based optical system design. Information maximization and bit-error-rate
      minimization both are possible with the new radially weighted encircled-energy
      merit function. We demonstrate the use of this new merit function through a
      design example and show that the information throughput is increased by 8% and
      the bit-error rate is reduced by 36% when compared with systems designed with
      traditional criteria.

PMID- 18345072
TI  - Information metric as a design tool for optoelectronic imaging systems.
AB  - The resolution of images acquired by a digital camera is limited to the camera's
      sampling interval. The images' visual quality is affected by the level of the
      degradations caused by the imaging process from acquisition to display, including
      quantization, coding, transmission, and digital filtering. The information metric
      is presented as a design and an assessment tool for high-resolution digital
      imaging systems and all their subsystems. It associates gains in the acquired
      information with improvements in resolution, sharpness, and clarity of the final
      image representation. It demonstrates the need to integrate a digital filtering
      module that accounts for the optoelectronic imaging degradations in the
      optoelectronic imaging design and assessment. It further demonstrates the
      metric's sensitivity by the assessment of the combined imaging processes as a
      unified system.

PMID- 18345073
TI  - Bandwidth optimization of optical data links by use of error-control codes.
AB  - A design approach to optimizing the bandwidth of optical data links while
      simultaneously decreasing the bit-error rate is proposed. Mathematical analysis
      indicates that bandwidth gains by factors of 10-60 with power gains of as much as
      8.9 dB are possible. To achieve these performance levels requires several
      innovations. First, conventional forward error-correcting codes cannot be used
      because of their excessive hardware cost. A reasonably powerful multidimensional
      parity-based error-control code is proposed and analyzed. These codes offer
      excellent error detection and moderate error-correction capabilities. Most
      importantly, they can operate at the fast clock rates that are required. Second,
      a hybrid automatic-repeat-request protocol is exploited to correct complex error
      patterns. In thermal-noise-limited systems this unique combination allows the
      optical clock rate to be increased significantly, thereby resulting in large
      bandwidth increases. The proposed design approach can be used in optical data
      links in which propagation delays are moderate and is applicable to fibers that
      exploit wavelength-division multiplexing or time-division multiplexing, one
      dimensional parallel-fiber ribbons, and two-dimensional optical data links that
      use free space or guided waves. Several design examples are illustrated.

PMID- 18345074
TI  - Capacity of the low-photon-rate direct-detection optical pulse-position
      modulation channel in the presence of noise photons.
AB  - We derive expressions for the capacity of the pulse-position-modulated (PPM)
      direct-detection photon-counting channel in the presence of noise photons in
      addition to the signal-dependent shot noise that is normally considered in
      studying photon counting at low photon rates. We note that even a small mean
      number of noise photons per PPM count bin significantly decreases the capacity of
      the channel. These results are useful for comparisons of performance that are
      obtained by use of real coding and synchronization algorithms with photon
      counting PPM schemes that are currently being considered for deep-space optical
      communications.

PMID- 18345075
TI  - Approximations to ideal-observer performance on signal-detection tasks.
AB  - The ideal-observer performance, as measured by the area under the receiver's
      operating characteristic curve, is computed for six examples of signal-detection
      tasks. Exact values for this quantity, as well as approximations based on the
      signal-to-noise ratio of the log likelihood and the likelihood-generating
      function, are found. The noise models considered are normal, exponential,
      Poisson, and two-sided exponential. The signal may affect the mean or the
      variance in each case. It is found that the approximation from the likelihood
      generating function tracks well with the exact area, whereas the log-likelihood
      signal-to-noise approximation can fail badly. The signal-to-noise ratio of the
      likelihood ratio itself is also computed for each example to demonstrate that it
      is not a good measure of ideal-observer performance.

PMID- 18345076
TI  - Channel reduction and applications to image processing.
AB  - Oftentimes when one is dealing with digital color images it is desired that some
      sort of image processing be performed on the spatial information. Current methods
      require that one process each of the channels (also called planes or colors) of
      an image separately, which increases the number of computations significantly. A
      novel, to our knowledge, approach to reducing the number of channels in a color
      image is presented. The channel-reduction process is intended to facilitate such
      color image-processing situations essentially by the separation of the spectral
      information from the spatial information, as in a paint-by-numbers picture. In
      this case the image processing need be applied only to a single channel of data
      and the color added afterward. With a compression ratio of slightly less than 3:1
      the method is not intended to compete with existing compression methods but
      rather to permit the processing of images in a compressed state.

PMID- 18345077
TI  - Three-dimensional image compression with integer wavelet transforms.
AB  - A three-dimensional (3-D) image-compression algorithm based on integer wavelet
      transforms and zerotree coding is presented. The embedded coding of zerotrees of
      wavelet coefficients (EZW) algorithm is extended to three dimensions, and context
      based adaptive arithmetic coding is used to improve its performance. The
      resultant algorithm, 3-D CB-EZW, efficiently encodes 3-D image data by the
      exploitation of the dependencies in all dimensions, while enabling lossy and
      lossless decompression from the same bit stream. Compared with the best available
      two-dimensional lossless compression techniques, the 3-D CB-EZW algorithm
      produced averages of 22%, 25%, and 20% decreases in compressed file sizes for
      computed tomography, magnetic resonance, and Airborne Visible Infrared Imaging
      Spectrometer images, respectively. The progressive performance of the algorithm
      is also compared with other lossy progressive-coding algorithms.

PMID- 18345078
TI  - Volume-consumption comparisons of free-space and guided-wave optical
      interconnections.
AB  - We compare volume-consumption characteristics of free-space and guided-wave
      optical interconnections. System volume consumption is used as a fundamental
      measure of various point-to-point space-invariant and space-variant
      interconnections of two-dimensional arrays of N(1/2) x N(1/2) points. We show
      that, in free-space and space-invariant situations, although volume consumption
      for macroaperture optics is O1(N(3/2)), where O denotes the order, it is only
      O2(N) for microaperture optics. For free-space and space-variant operations only
      microaperture optics is possible without fundamental power losses. The
      corresponding minimum volume consumption is O3(N3). We show that single
      microaperture-per-channel implementations of either space-invariant or space
      variant operations are, in general, more volume efficient than are their two
      cascade microaperture-per-channel counterparts. We also show that, for minimizing
      volume consumption, the optimum relative apertures F#(opt) for space-variant
      optical elements are, respectively, (5N)(1/2)/4 for a single microaperture-per
      channel geometry and (5N)(1/2)/2 for a two-cascade microaperture-per-channel
      geometry. In guided-wave or fiber interconnect cases our study shows that the
      volume consumption for space-invariant and space-variant operations is O4(N),
      with O4 < O2, and O5(N(3/2)), respectively. Thus an important conclusion of the
      study is that free-space optics is less volume efficient than is guided-wave
      optics in both space-invariant and space-variant interconnect applications.

PMID- 18345079
TI  - Three-dimensional optical data storage in a fluorescent dye-doped photopolymer.
AB  - We propose a new, to our knowledge, monolithic multilayer optical storage medium
      in which data may be stored through the diffusional redistribution of fluorescent
      molecules within a polymer host. The active portion of the medium consists of a
      photopolymer doped with a fluorescent dye that is polymerized at the focal point
      of a high-numerical-aperture lens. We believe that as fluorescent molecules bond
      to the polymer matrix they become more highly concentrated in the polymerized
      regions, resulting in the modulated data pattern. Since data readout is based on
      detection of fluorescence rather than index modulation as in other photopolymer
      based memories, the problems of media shrinkage and optical scatter are of less
      concern. An intensity threshold observed in the recording response of this
      material due to the presence of inhibitor molecules in the photopolymer allows
      for the three-dimensional confinement of recorded bits and therefore multilayer
      recording. The nonlinear recording characteristics of this material were
      investigated through a simple model of photopolymerization and diffusion and
      verified experimentally. Both single-layer and multilayer recordings were
      demonstrated.

PMID- 18345080
TI  - Three-dimensional holographic stamping of multilayer bit-oriented nonlinear
      optical media.
AB  - The requirements and limitations on the use of a volume holographic element for
      the simultaneous optical stamping of multilayer data into a three-dimensional
      (3D) bit-oriented material that exhibits a suitable sensitivity threshold are
      investigated. The expected performance of such a holographic stamping element is
      examined through a model of the coherent noise effects that result from the
      interference of the many data layers with one another. We show that higher signal
      to-noise values may be achieved through the use of semicoherent light during the
      readout of the hologram. The main limitations to this technique arise from the
      bandwidth requirements on the holographic element, the degree of nonlinearity
      required of the bit-oriented media, and the tolerance requirements for the
      optical exposure levels. As a demonstration of the concept, a two-layer stamping
      element is fabricated and used to simultaneously stamp two layers of data into a
      3D dye-doped photopolymer storage medium.

PMID- 18345082
TI  - Wave optics simulation of atmospheric turbulence and reflective speckle effects
      in CO2 lidar.
AB  - Laser speckle can influence lidar measurements from a diffuse hard target.
      Atmospheric optical turbulence will also affect the lidar return signal. We
      present a numerical simulation that models the propagation of a lidar beam and
      accounts for both reflective speckle and atmospheric turbulence effects. Our
      simulation is based on implementing a Huygens-Fresnel approximation to laser
      propagation. A series of phase screens, with the appropriate atmospheric
      statistical characteristics, are used to simulate the effect of atmospheric
      turbulence. A single random phase screen is used to simulate scattering of the
      entire beam from a rough surface. We compare the output of our numerical model
      with separate CO(2) lidar measurements of atmospheric turbulence and reflective
      speckle. We also compare the output of our model with separate analytical
      predictions for atmospheric turbulence and reflective speckle. Good agreement was
      found between the model and the experimental data. Good agreement was also found
      with analytical predictions. Finally, we present results of a simulation of the
      combined effects on a finite-aperture lidar system that are qualitatively
      consistent with previous experimental observations of increasing rms noise with
      increasing turbulence level.

PMID- 18345083
TI  - Self-shading of upwelling irradiance for an instrument with sensors on a sidearm.
AB  - The self-shading measurement error of the upwelling irradiance that is due to the
      presence of the instrument housing of an optical spectrometer with the irradiance
      meter located on a sidearm was calculated with a Monte Carlo code. The dependence
      of the effect on the instrument dimensions, the values of real optical
      parameters, sea-surface roughness, and Sun zenith angle were all studied to
      estimate maximum errors for two possible configurations of a proposed new marine
      spectrophotometer.

PMID- 18345084
TI  - Microphysical particle parameters from extinction and backscatter lidar data by
      inversion with regularization: experiment.
AB  - We present effective radius, volume, surface-area, and number concentrations as
      well as mean complex refractive index of tropospheric particle size distributions
      based on lidar measurements at six wavelengths. The parameters are derived by
      means of an inversion algorithm that has been specifically designed for the
      inversion of available optical data sets. The data were taken on 20 June and on
      20 July 1997 during the Aerosol Characterization Experiment ACE 2 (North
      Atlantic/Portugal) and on 9 August 1998 during the Lindenberg Aerosol
      Characterization Experiment LACE 98 (Lindenberg/Germany). Measurements on 20 June
      1997 were taken in a clean-marine boundary layer, and a large value of 0.64
      microm for the effective radius, a low value of 1.45 for the real part, and a
      negligible imaginary part of the complex refractive index were found. The single
      scatter albedo was 0.98 at 532 nm. It was derived from the particle parameters
      with Mie-scattering calculations. In contrast, the particles were less than 0.2
      microm in effective radius in a continental-polluted aerosol layer on 20 July
      1997. The real part of the complex refractive index was approximately 1.6; the
      imaginary part showed values near 0.03i. The single-scatter albedo was 0.84. On 9
      August 1998 an elevated particle layer located from 3000 to 6000 m was observed,
      which had originated from an area of biomass burning in northwestern Canada. Here
      the effective radius was approximately 0.24 mum, the real part of the complex
      refractive index was above 1.6, the imaginary part was approximately 0.04i, and
      the single-scatter albedo was 0.81. Excellent agreement has been found with
      results based on sunphotometer and in situ measurements that were performed
      during the field campaigns.

PMID- 18345085
TI  - Application of the Raman scattering coefficient of water to calculations in
      marine optics.
AB  - The relation between the total Raman scattering coefficient of water (b(r)) and
      the Raman scattering cross section of liquid water is clarified. Consideration of
      the experimental configurations used to derive the Raman scattering cross section
      of water relative to benzene leads to a revised value of b(r) for water. In
      certain applications in marine optics it is necessary to scale b(r) to effect a
      change from implicit units of energy to quanta.

PMID- 18345086
TI  - Lidar inelastic multiple-scattering parameters of cirrus particle ensembles
      determined with geometrical-optics crystal phase functions.
AB  - Multiple-scattering correction factors for cirrus particle extinction
      coefficients measured with Raman and high spectral resolution lidars are
      calculated with a radiative-transfer model. Cirrus particle-ensemble phase
      functions are computed from single-crystal phase functions derived in a
      geometrical-optics approximation. Seven crystal types are considered. In cirrus
      clouds with height-independent particle extinction coefficients the general
      pattern of the multiple-scattering parameters has a steep onset at cloud base
      with values of 0.5-0.7 followed by a gradual and monotonic decrease to 0.1-0.2 at
      cloud top. The larger the scattering particles are, the more gradual is the rate
      of decrease. Multiple-scattering parameters of complex crystals and of imperfect
      hexagonal columns and plates can be well approximated by those of projected-area
      equivalent ice spheres, whereas perfect hexagonal crystals show values as much as
      70% higher than those of spheres. The dependencies of the multiple-scattering
      parameters on cirrus particle spectrum, base height, and geometric depth and on
      the lidar parameters laser wavelength and receiver field of view, are discussed,
      and a set of multiple-scattering parameter profiles for the correction of
      extinction measurements in homogeneous cirrus is provided.

PMID- 18345087
TI  - Effects of time averaging on optical scintillation in a ground-to-satellite
      atmospheric propagation.
AB  - Temporal natures for a variance of turbulence-induced log-intensity fluctuations
      are obtained. The variance of the optical fluctuation is reduced when the optical
      signals are integrated in a photodetector, and we express the index of reduction
      (called the time-averaging factor) by using an autocovariance function of the
      optical fluctuation. The optical fluctuations for a ground-to-satellite path are
      caused by both atmospheric turbulence and the beam-pointing jitter error of the
      optical transmitter. The turbulence-induced optical scintillation can be
      discriminated from the fluctuation that is due to the beam-pointing jitter error.
      The compared result from the probability density function of the optical signal
      reveals good agreement. The temporal autocovariance functions of optical
      scintillation are obtained and used to calculate the time-averaging factor. The
      analytically expected effects of time averaging are verified by the experimental
      results. The estimations contribute to the link budget design for the optical
      tracking channel through atmospheric turbulence.

PMID- 18345088
TI  - Understanding profile-induced group-delay ripple in Bragg gratings.
AB  - The relationship between group-delay ripple and the apodization profile of
      chirped Bragg gratings is analyzed. Simple physical explanations are given for
      departures from ideal linear group delay by use of only the concepts of
      reflection at discontinuities and band gaps and the optical path lengths of
      cavities. Quantitative expressions are obtained for the amplitudes, phases, and
      periods of both the fast and slow components of the ripple.

PMID- 18345089
TI  - Comparison of isochronal and isothermal decays of bragg gratings written through
      continuous-wave exposure of an unloaded germanosilicate fiber.
AB  - We compare the results of thermally induced isochronal and isothermal decays of
      fiber Bragg gratings written through cw exposure of an unloaded germanosilicate
      fiber. We show that isochronal step decays can be used to predict isothermal
      decays, provided that some corrections are carried out to take into account a
      reversible change in grating reflectivity induced by the increase of the fiber
      temperature. The isochronal accelerated-aging method enables one to sample most
      of the initial distribution of trapped site energies in a fairly short time.
      Taking advantage of this property of the method, we show that the initial
      distribution for a weak grating is similar to those for stronger gratings. The
      consequences of this observation are discussed within the framework of the
      various reaction pathway model.

PMID- 18345090
TI  - Design and tolerance analysis of a router with an amplified resonator and Bragg
      gratings.
AB  - A novel ring resonator configuration with Bragg gratings is presented. The
      stability of this configuration is studied by a z-transform technique. A router
      design with a FWHM of 17 MHz, a -40-dB rejection ratio, and a 15-dB gain at the
      output port is reported. The influence of temperature and of fabrication
      tolerance on parameters of this router configuration implemented with fiber
      technology is reviewed. Deviations in design specification owing to parameter
      variations are studied and compensated for with a gain control of 2.4% in a
      specific design.

PMID- 18345091
TI  - Measurement of ultralow supermirror birefringence by use of the polarimetric
      differential cavity ringdown technique.
AB  - We demonstrate a novel technique for measuring ultralow linear birefringence of
      supermirrors (high-reflectivity dielectric mirror coatings). The polarimetric
      cavity ringdown technique is used in conjunction with the differential detection
      scheme with circular polarization to enhance the measurement sensitivity. The
      technique could, in principle, provide the convenience and reliability of linear
      detection signals and a reasonable tolerance to experimental imperfections. Phase
      retardation and orientation of each cavity mirror can be determined separately
      without the influence of the other mirror. The minimum detectable phase
      retardation achieved experimentally with this technique is ~6 x 10(-8) rad.

PMID- 18345092
TI  - Observation of stable cylindrical modes in electrically pumped circular grating
      coupled surface-emitting lasers.
AB  - We present the results of a comprehensive experimental study of the modal
      behavior of electrically pumped circular grating-coupled surface-emitting lasers
      with resonant second-order gratings. Our results show stable cylindrical mode
      operation with azimuthal orders m = 1 and m = 52. We have found that, when a
      passive, unpumped 0.7-microm-deep indentation is included at the center of the
      circular resonator contact, the modal behavior becomes more stable with respect
      to increasing current. This result manifests itself in the lasing of two
      orthogonal m = 1 modes along with one higher-order mode from threshold to 2.2
      times threshold or more. The spatial coherence of the cylindrical modes over the
      area of the resonator leads to better beam quality. Lasers without passive
      central indentations exhibit mode hopping between quasi-linear modes and higher
      order cylindrical modes as the current is increased.

PMID- 18345093
TI  - Wave-front control of a large-aperture laser system by use of a static phase
      corrector.
AB  - In large-aperture, ultrahigh-intensity laser systems, such as Vulcan at the
      Rutherford Appleton Laboratory, one of the most important factors that determines
      the ultimate on-target focused intensity is the wave-front quality of the laser
      pulse. We report on a wave-front analysis carried out on Vulcan to determine the
      nature and contribution of the aberrations present in the laser pulse that
      effectively limited the available on-target intensity. We also report on a
      significant improvement to the wave-front quality that was achieved by static
      correction of the main aberration, resulting in an increase of focused
      intensities by a factor of 4.

PMID- 18345094
TI  - Passive Q switching of a solar-pumped Nd:YAG laser.
AB  - Passive Q switching is a preferable choice for switching the Q factor of a solar
      pumped laser because it requires neither a driver nor an electrical power supply.
      The superior thermal characteristics and durability of Cr(4+):YAG single crystals
      as passive Q switches for lamp and diode-pumped high-power lasers has been
      demonstrated. Here we report on an average power of 37 W and a switching
      efficiency of 80% obtained by use of a solar-pumped Nd:YAG laser Q switched by a
      Cr(4+):YAG saturable absorber. Concentration of the pumping solar energy on the
      laser crystal was obtained with a three-stage concentrator, composed of 12
      heliostats, a three-dimensional compound parabolic concentrator (CPC) and a two
      dimensional CPC. The water-cooled passive Q switch also served as the laser rear
      mirror. Repetition rates of as much as 50 kHz, at pulse durations between 190 and
      310 ns (FWHM) were achieved. From the experimental results, the saturated single
      pass power absorption of the Cr(4+):YAG device was estimated as 3 ? 1%.

PMID- 18345095
TI  - Numerical analysis of the transmission efficiency of heat-drawn and chemically
      etched scanning near-field optical microscopes.
AB  - The scanning near-field optical microscope (SNOM) has been tested experimentally
      for a wide variety of applications, but, to date, there has been little work done
      on the numerical or analytical modeling of the optical field as it propagates
      throughout the SNOM probe. Therefore, the fabrication on the probes relies more
      on trial and error than on clear design principles. An algorithm has been
      developed for the study and optimization of the geometry of SNOM probes
      fabricated by the heat-drawn and the one-step chemically etched methods. The
      algorithm uses the finite-difference beam propagation method (FD-BPM) to model
      the field evolution throughout the SNOM structure.

PMID- 18345096
TI  - Method for the reduction of signal-induced noise in photomultiplier tubes.
AB  - A new method to reduce photomultiplier tube detector signal-induced noise (SIN)
      in a lidar system is successfully demonstrated. A metal ring electrode placed
      external to the photomultiplier tube photocathode is pulsed during the intense
      near-field lidar return with a potential between 15 and 500 V, resulting in a
      significant reduction in SIN. The effect of the metal ring voltage on the decay
      time constant and the magnitude of a simulated lidar signal is presented. Optimal
      experimental conditions for the use of this device in lidar receivers, such that
      the lidar decay time constant is not affected, are determined. Mechanisms for
      this SIN suppression system are discussed in detail, and data were recorded to
      show that the voltage on the metal ring functions by altering the photomultiplier
      electron optics.

PMID- 18345097
TI  - Moderate resolution study of the ground-based passive emission of ozone.
AB  - Information from a ground-based passive remote-sensing system that measures ozone
      profile concentrations with a moderate 4-cm(-1) spectral resolution is evaluated.
      A theoretical study of the best choice for the wave numbers and zenith angles for
      the line of sight is presented. The superimposed water emission is analyzed for
      the selected wave numbers, and possibilities of separating the contributions of
      water and ozone to the radiance received are studied. Tropospheric and
      stratospheric ozone can be sounded by appropriate selection of the experimental
      conditions.

PMID- 18345098
TI  - Shape characterization of a large nonspherical particle by use of its Fraunhofer
      diffraction pattern.
AB  - We characterize the shape of a large nonspherical particle by means of the two
      dimensional Fourier transformation of its diffraction pattern, called the S
      function. The main properties of S functions are considered. Some ways in which
      to retrieve the geometric parameters of a particle by use of its S function are
      discussed. In particular, the parameter of nonsphericity of a particle is defined
      by means of the S function.

PMID- 18345099
TI  - Investigation of an optical limiting mechanism in multiwalled carbon nanotubes.
AB  - We report our investigation of the mechanism that is responsible for the optical
      limiting behavior in multiwalled carbon nanotubes. We conducted energy-dependent
      transmission measurements, picosecond time-resolved pump-probe experiment, and
      nonlinear scattering experiments at 532-nm wavelength on multiwalled carbon
      nanotube suspension. For comparison, C(60)-toluene solutions and carbon black
      suspensions were also studied in the same experiments. The similarities that we
      observed between the multiwalled carbon nanotubes and carbon black suspension
      suggest that nonlinear scattering, which is known to be responsible for the
      limiting action in carbon black suspension, should play an important role in the
      limiting effect in multiwalled carbon nanotubes.

PMID- 18345100
TI  - Experimental investigation of saturated polarization spectroscopy for
      quantitative concentration measurements.
AB  - Polarization-spectroscopy (PS) line shapes and signal intensities are measured in
      well-characterized hydrogen-air flames operated over a wide range of equivalence
      ratios. We use both low (perturbative) and high (saturating) pump beam
      intensities in the counterpropagating pump-probe geometry. The effects of
      saturation on the line-center signal intensity and the resonance linewidth are
      investigated. The PS signal intensities are used to measure relative OH number
      densities in a series of near-adiabatic flames at equivalence ratios (phi)
      ranging from 0.5 to 1.5. The use of saturating pump intensities minimizes the
      effect of pump beam absorption, providing more accurate number density
      measurements. When calibrated to the calculated OH concentration in the phi = 0.6
      flame, the saturated PS number density measurements probing the P(1)(2)
      transition are in excellent agreement with OH absorption measurements,
      equilibrium calculations of OH number density, and previous saturated degenerate
      four-wave mixing OH number density measurements.

PMID- 18345101
TI  - Multiplexed continuous-wave diode-laser cavity ringdown measurements of multiple
      species.
AB  - Rapid cavity ringdown measurements of multiple broadband absorbing species
      (methanol and isopropanol) in gas mixtures have been recorded with two
      multiplexed continuous-wave distributed-feedback diode lasers operating near 1.4
      mum. A measurement sensitivity of 2.4 x 10(-9) cm(-1) for a 4.3-s averaging time
      was achieved in a 39.5-cm-long static cell with 99.94% reflectivity mirrors. This
      corresponds to a water-vapor detection limit of less than 2 ppb (parts in 10(9))
      for the strong H(2)O lines near 1.4 mum. The shot-to-shot noise of the decay time
      constant tau was approximately 0.3-0.7%, and ringdown acquisition rates as great
      as 900 Hz were achieved.

PMID- 18345102
TI  - Propagation of light trapped within a set of lowest-order modes of graded-index
      multimode fiber undergoing bending.
AB  - We describe experimental results and a theoretical analysis for propagation in
      graded-index multimode fiber when diode laser light is launched into the lowest
      order propagation modes and the fiber undergoes severe bending perturbations.
      Experimentally, near-field modal interference images and transmission loss
      measurements were obtained for different loop diameters. The data indicate that,
      when the fundamental mode is excited, the light remains in lowest-order modes
      even for small bend diameters. This is consistent with analysis which predicts
      that, in a parabolic-index multimode fiber subject to constant diameter bending,
      the light tends to oscillate between lowest-order modes and remains trapped
      therein rather than diffusing to high-order modes. Implications of these results
      for an intrusion-resistant communication system with graded-index multimode fiber
      are discussed.

PMID- 18345103
TI  - Control of the characteristics of a long-period grating by cladding etching.
AB  - We have analyzed the effects of the fiber cladding radius on the characteristics
      of long-period fiber gratings. By etching the cladding of a common single-mode
      fiber, we verified the characteristics experimentally. When by etching we reduce
      the cladding radius of a common single-mode fiber on which a long-period
      refractive-index modulation has been imposed, the coupling strength of the core
      and the cladding modes increases. In addition, the difference in the propagation
      constants (for a fixed wavelength) between the core mode and the cladding modes
      increases; hence the resonant transmission dip wavelengths shift to longer
      wavelengths. The proposed method can be useful in making and detuning long-period
      fiber grating filters.

PMID- 18345104
TI  - Model for quantifying photoelastic fringe degradation by imperfect
      retroreflective backings.
AB  - In any automated algorithm for interpreting photoelastic fringe patterns it is
      necessary to understand and quantify sources of error in the measurement system.
      We have been considering how the various components of the coating affect the
      photoelastic measurement, because this source of error has received fairly little
      attention in the literature. Because the reflective backing is not a perfect
      retroreflector, it does not preserve the polarization of light and thereby
      introduces noise into the measurement that depends on the angle of obliqueness
      and roughness of the reflective surface. This is of particular concern in
      resolving the stress tensor through the combination of thermoelasticity and
      photoelasticity where the components are sensitive to errors in the principal
      angle and difference of the principal stresses. We have developed a physical
      model that accounts for this and other sources of measurement error to be
      introduced in a systematic way so that the individual effects on the fringe
      patterns can be quantified. Simulations show altered photoelastic fringes when
      backing roughness and oblique incident angles are incorporated into the model.

PMID- 18345105
TI  - Optimization of resolution and color reproduction by controlling luminance and
      contrast levels of a liquid-crystal display monitor.
AB  - The image quality of a color liquid-crystal display monitor is studied by
      changing the contrast and the luminance levels. The resolution is assessed with
      modulation transfer function area (MTFA) that is measured at nine different
      combinations of the luminance and contrast. At these combinations, we measure the
      chromaticity coordinates and luminance of red-green-blue channels as a function
      of the digital-analog convert value. We analyze the relations among MTFA value,
      constant-channel chromaticity, color gamut, and maximum luminance of a white
      pattern. From the results, the combination of levels is found that provides both
      high resolution and good color reproduction.

PMID- 18345106
TI  - Method for measuring veiling glare in high-performance display devices.
AB  - An experimental method for measuring the veiling glare characteristics of display
      devices is presented. The measured veiling glare ratio (G) is taken to be the
      luminance in the surrounding bright field divided by the luminance in a dark
      circle. The method is based on a collimated conic probe that minimizes signal
      contamination from bright surroundings allowing for measurements of low luminance
      in a circular dark spot of a test pattern. A correction factor computed with test
      patterns having opaque spots is introduced. The factor is expressed as a
      bivariate function of the dark-spot radius and the distance between the probe and
      the emissive surface. We studied the uncertainty introduced by the method by
      measuring veiling glare test patterns printed on radiographic film for which the
      transmission of the dark spots was determined experimentally. Performance
      characterization measurements show that signal contamination is less than 10(-4)
      of the bright field surrounding a dark circle. Our results show that G of a few
      hundred can be measured with an uncertainty of a few percent, and ratios of
      approximately 10(3) can be reported within 10%. Finally, we demonstrate the
      method by measuring G for a high-performance monochrome cathode-ray tube display.

PMID- 18345107
TI  - Optical plastic refractive measurements in the visible and the near-infrared
      regions.
AB  - Some new refractometric results are obtained in the visible and the near-infrared
      spectral regions. The main optical plastics are analyzed: poly(methyl
      methacrylate), polystyrene, polycarbonate, and styrene acrylonitrile. New
      materials, such as methyl methacrylate styrene copolmer, CTE-Richardson, Zeonex,
      Optorez, and Bayer are examined. The refractive indices are measured for
      wavelengths from 435.8 to 1052 nm with a new device. Abbe constants and
      dispersion coefficients are calculated. The measured and computed data is
      intended for designers and technologists.

PMID- 18345108
TI  - Anisotropic incoherent reflection model for spectroscopic ellipsometry of a thick
      semitransparent anisotropic substrate.
AB  - An anisotropic incoherent reflection model for the Mueller matrix elements of an
      optically thick uniaxial anisotropic semitransparent substrate with its
      anisotropy axis along its surface normal is developed. The Mueller matrix
      elements are measured by phase-modulated spectroscopic ellipsometry (SE) and
      compared with incoherent reflection model simulations. In the case of a sapphire
      substrate the oscillations observed are accurately modeled, and, in addition, the
      oscillating degree of polarization is correctly predicted. A straightforward
      generalization of the optical model, in the case of an arbitrary stack of layers
      containing a thick anisotropic semitransparent substrate, is also proposed and
      experimentally validated. The model is further applied to study the anisotropic
      dielectric function of a semi-insulating 4H-SiC wafer. An approximation based on
      a simple variation in the optical transition element is proposed to model the SiC
      birefringence. In conclusion, SE is shown to be a powerful alternative for
      investigating and predicting the behavior of optically thick birefringent
      materials.

PMID- 18345109
TI  - Phase retardometer: a proposed device for measuring phase retardance.
AB  - The realization of a standard device for measuring phase retardance has been
      retarded by the lack of a simple underlying physical concept that can be
      formulated in a simple mathematical expression to provide quick, direct, and
      accurate results. A proposed device that meets these requirements and simple
      formulas for retardance measurements are presented.

PMID- 18345110
TI  - Visualization of two-dimensional phase gradients by subtraction of a reference
      periodic pattern.
AB  - We describe a simple method for visualization of phase objects. The phase object
      is placed between a printed two-dimensional periodic pattern and a CCD camera.
      The ray deflection that is due to the phase object distorts the image of the
      pattern. This image is subtracted from a reference image and then, by squaring
      and low-pass filtering, a measurement of the two-dimensional refractive-index
      changes is obtained. Because the optical system does not require special
      alignment or illumination, the method presented has potential application for
      detection of gas leaks in industrial environments.

PMID- 18345111
TI  - Effects of Unparallel Grating Planes in Talbot Interferometry. II.
AB  - The properties of the moire fringes in Talbot interferometry are analyzed for a
      small inclined angle beta between the two grating planes, which is produced by
      rotation of the beam splitter grating about the axis perpendicular to the lines
      of the grating. Theoretical analyses indicate that the tilt angle of the
      resultant moire fringes is less sensitive to beta than when the small inclined
      angle is formed by rotation of the beam splitter grating about the axis parallel
      to the lines direction of the grating as described earlier [Appl. Opt. 38, 4111
      (1999)] and that contrast of the moire fringes decreases with an increase in beta
      or in the spatial frequency of the grating and may result in impaired measurement
      accuracy. The validity of the theoretical analyses is illustrated by experiments.

PMID- 18345112
TI  - Real-time holographic interferometry with double two-wave mixing in
      photorefractive crystals.
AB  - We present a real-time holographic interferometer for which two reference waves
      of different phases are created by two-wave mixing with a stationary signal wave
      in a photorefractive crystal. These waves are reconstructions of the stationary
      signal wave and interfere with the momentary (changing) signal wave in the manner
      of a holographic real-time interferometer. A fast change (phase or intensity) of
      the signal wave leads to different intensity changes in both interferograms that
      are jointly used for evaluation. With an electric dc field applied to the
      crystal, a high sensitivity for measuring phase changes (down to lambda/50,
      lambda = 633 nm) is found, and the sign of the phase change can be determined.

PMID- 18345113
TI  - Fringe modulation skewing effect in white-light vertical scanning interferometry.
AB  - An interference fringe modulation skewing effect in white-light vertical scanning
      interferometry that can produce a batwings artifact in a step height measurement
      is described. The skewing occurs at a position on or close to the edge of a step
      in the sample under measurement when the step height is less than the coherence
      length of the light source used. A diffraction model is used to explain the
      effect.

PMID- 18345114
TI  - Improved vertical-scanning interferometry.
AB  - We describe a method that combines phase-shifting and coherence-peak-sensing
      techniques to permit measurements with the height resolution of phase-shifting
      interferometry without the interval-slope limitation of lambda/4 per data sample
      of phase-shifting interferometry. A five-frame algorithm is used to determine
      both the best-focus frame position and the fractional phase from the best-focus
      frame of the correlogram acquired through vertical scanning. The two surface
      profiles retrieved from the phase and the modulation contrast of the correlograms
      are compared in the phase-unwrapping process to remove fringe-order ambiguity.

PMID- 18345115
TI  - Reflective grating interferometer in a noncollimated configuration.
AB  - A third-order aberration analysis for a reflective grating interferometer (RGI)
      is developed for a noncollimated configuration. In such a configuration the RGI
      is still a folded and reversing interferometer that is sensitive only to coma
      aberration, as it is in the collimated configuration. However, for an unaberrated
      input beam converging on a plane grating, the reflective grating of the
      interferometer introduces self-aberrations. Consequently, a nonnull fringe
      pattern is obtained. Nevertheless, a RGI in the noncollimated configuration has
      the potential to be applied for isolating and measuring coma, and a possible
      configuration for this application is proposed. As an example of the application,
      the coma of a large mirror could be isolated and measured by use of a converged
      configuration to avoid the main limitation in using the RGI in a configuration
      with a nearly collimated beam.

PMID- 18345116
TI  - Interference imaging for aspheric surface testing.
AB  - Peak-valley accuracy of lambda/20 over a range of 2lambda is not unusual in an
      interferometric null test. For the larger dynamic ranges of a nonnull test,
      however, the fringe-imaging optics degrades the accuracy. We classify the errors
      introduced and analyze them in the context of both general and third-order
      aberration theory. We can predict the measurement error from known interferometer
      parameters, and we illustrate this for a single mirror. The errors are tabulated
      for the specific case of a fourth-order asphere with 100 mum of sag. We show that
      the third-order approximation is comparable with exact ray-trace results for this
      case.

PMID- 18345117
TI  - Integrated Optics for Astronomical Interferometry. III. Optical Validation of a
      Planar Optics Two-Telescope Beam Combiner.
AB  - The optical characterization of a fiber-connected planar optics beam combiner
      dedicated to astronomical interferometry for two telescopes is presented. The
      beam combiner, fully integrated on a single 5 mm x 40 mm glass chip, is tested as
      the central part of an astronomical instrument. The single-mode waveguides are
      made by silver-ion-exchange technology upon glass substrates and provide spatial
      filtering, which improves the visibility measurement accuracy by selecting only
      the fundamental mode of the beams at the telescope focal plane. A global optical
      throughput of 43% is measured, and the sources of losses are identified and
      examined in detail. Solutions for improving this throughput are proposed. High
      and stable contrasts are obtained with a 1.55-mum laser diode (?96%) and with a
      white-light source (~92%) in the astronomical H filter (1.43 mum; 1.77 mum). The
      need for accurate control of differential instrumental polarization is
      demonstrated. In this context the intrinsic polarization-maintaining property of
      the planar optics component is characterized. This validation of the important
      potential uses of integrated planar optics should be valuable for future design
      of optical telescope arrays.

PMID- 18345118
TI  - Monitoring of Multimode Imaging Devices by use of Optical Low-Coherence
      Reflectometers in Reflection and Transmission Modes.
AB  - The broadband source of a high-precision optical low-coherence reflectometer is
      simultaneously employed in conventional reflection and transmission modes to
      monitor the internal properties of multimode imaging (MMI) devices. Using two
      carefully chosen examples, we show that this new methodology should permit
      precise assessment of the performance of MMI devices, including backreflection
      and internal reflection as well as the imbalance between output waveguides.

PMID- 18345119
TI  - Nonparaxial diffraction-limited propagation of light in a graded-index planar
      medium with a hyperbolic secant refractive-index profile.
AB  - Nonparaxial diffraction-limited propagation of light with amplitude distribution
      in hyperbolic functions through an inhomogeneous planar medium with a hyperbolic
      secant refractive-index profile is studied by means of the stationary phase
      method. The irradiance distribution at geometrical shadow, edge of shadow, and a
      geometrically illuminated region is analyzed for a particular case.

PMID- 18345120
TI  - Variation on Zernike's phase-contrast microscope.
AB  - We describe the design, construction, and testing of a variant of Zernike's phase
      contrast microscope. The sample is illuminated with a white-light source through
      an annular aperture, which is projected onto the entrance pupil of the objective
      lens. In the return path the light diffracted by the sample and appearing in the
      interior of the objective's aperture (i.e., the test beam) is separated from the
      light returning in the annular region near the rim of the objective (i.e., the
      reference beam). The separated beams are relatively phase shifted and then
      combined to create an interferogram of the sample's surface on a CCD camera. It
      is fairly straightforward to use this system as a conventional bright-field or
      dark-field microscope, but its most interesting application is as a Zernike phase
      contrast microscope with adjustable amplitude ratio and phase shift between test
      and reference beams. The ability to continuously adjust the phase of the
      reference beam also enables quantitative measurement of the phase imparted by the
      sample to the incident beam.

PMID- 18345121
TI  - Phase effects in double-focus and double-aperture interference microscopy.
AB  - Two different optical techniques for surface tracking and linewidth measurement
      are evaluated. First, an evaluation is made of the performance of a double-focus
      polarization microscope, based on results from a computer model and from
      experimental measurements. The assessment shows that a phase curvature effect
      makes the operation of this configuration impractical as a surface tracking
      device and linewidth measurement system. An alternative arrangement of using a
      double aperture is evaluated. The phase curvature effect is reduced in this type
      of microscope. A practical optical arrangement to implement a double-aperture
      microscope is given.

PMID- 18345122
TI  - Measurement of the relative optical phase between amorphous and crystalline
      regions of the phase-change media of optical recording.
AB  - We describe a method of measuring the relative optical phase on reflection
      between amorphous and crystalline regions of the phase-change media of optical
      data storage. With a red He-Ne laser (wavelength, 632.8 nm) the relative phases
      on two quadrilayer optical disk stacks were measured and found to be ~40 degrees
      . The results are in good agreement with the calculated values based on the known
      layer thicknesses and refractive indices of the stacks. For calibration purposes
      the height of a known step on an otherwise flat silicon substrate was measured
      with the same apparatus. The proposed method is fairly simple to set up, can
      measure both front-surface and through-substrate types of optical disk, and can
      be used with any laser that has long coherence length.

PMID- 18345123
TI  - Employment of reverse optimization to relax manufacturing tolerances imposed on
      system constructional parameters associated with complex optical systems.
AB  - I describe a practical method for facilitating the construction of a complex
      optical arrangement that was extremely sensitive to manufacturing defects. I
      discuss dealing with the actual tolerancing process employed and outline the
      reverse optimization technique adopted to take the necessary corrective action
      with regard to the lens to yield the performance specified. The optical design to
      which the techniques are addressed is that of a high-performance color-corrected
      scanner lens, capable of resolving 200 line pairs/mm over a 10-mm(2) object.

PMID- 18345124
TI  - Chemical cleaving method of relief microstructure formation on dichromated
      gelatin.
AB  - A chemical cleaving method to improve the resolution of relief modulation in
      dichromated gelatin is presented. The process (which uses hydroxylamine) yields
      higher relief resolution and better profile fidelity than a process that uses the
      enzyme trypsin because it has many fewer cleaving sites. Experiments prove that
      relief modulation can produce a resolution of as much as 500 lines/mm. With a
      projection exposure system, a microprism array with a 30-mum-wide, 0.8-mum-high
      cell is fabricated by this method. A method for forming a continuous relief on
      dichromated gelatin is also discussed.

PMID- 18345125
TI  - Design of multilayer extreme-ultraviolet mirrors for enhanced reflectivity.
AB  - We show numerically that the reflectivity of multilayer extreme-UV (EUV) mirrors
      tuned for the 11-14-nm spectral region, for which the two-component, Mo/Be and
      Mo/Si multilayer systems with constant layer thickness are commonly used, can be
      enhanced significantly when we incorporate additional materials within the stack.
      The reflectivity performance of the quarter-wavelength multilayers can be
      enhanced further by global optimization procedures with which the layer
      thicknesses are varied for optimum performance. By incorporating additional
      materials of differing complex refractive indices-e.g., Rh, Ru, Sr, Pd, and RbCl
      in various regions of the stack, we observed peak reflectivity enhancements of as
      much as ~5% for a single reflector compared with standard unoptimized stacks. We
      show that, in an EUV optical system with nine near-normal-incidence mirror
      surfaces, the optical throughput may be increased by a factor as great as 2. We
      also show that protective capping layers, in addition to protecting the mirrors
      from environmental attack, may serve to improve the reflectivity characteristics.

PMID- 18345126
TI  - Simple Estimates for the Effects of Mid-spatial-Frequency Surface Errors on Image
      Quality.
AB  - Mid-spatial-frequency surface errors can be introduced by various manufacturing
      processes. These errors bridge the gap between traditional figure and finish
      errors. Although the effects of mid-spatial-frequency errors on the imagery of an
      optical system can be modeled with a ray-based approach, simply tracing rays
      provides little insight. We present an alternative method that treats surface
      errors as perturbations to the nominal surface profile. This approach, combined
      with standard statistical methods, allows one to make simple back-of-the-envelope
      predictions of the effects of mid-spatial-frequency errors for various measures
      of optical performance. Two examples illustrating the effectiveness of this
      approach are presented.

PMID- 18345127
TI  - Design of pushbroom imaging spectrometers for optimum recovery of spectroscopic
      and spatial information.
AB  - A modulation transfer function-based optimization method is described that
      generates optimal spectral and spatial uniformity of response from compact
      pushbroom imaging spectrometer designs. Such uniformity is essential for
      extracting accurate spectroscopic information from a pushbroom imaging
      spectrometer for Earth-observing remote sensing applications. Two simple and
      compact spectrometer design examples are described that satisfy stringent
      uniformity specifications.

PMID- 18345128
TI  - Infrared intracavity laser absorption spectroscopy with a continuous-scan Fourier
      transform interferometer.
AB  - High-quality broadband infrared high-resolution spectra were obtained by use of
      the intracavity laser absorption spectroscopy technique with a Ti:sapphire laser
      in combination with a continuous-scan Fourier-transform (FT) interferometer. With
      electronic filtering used to smooth out the fluctuations of the laser power, the
      absorption of atmospheric water vapor in the range of 12,450-12,700 cm(-1) was
      recorded at a resolution of 0.05 cm(-1). A signal-to-noise ratio of greater than
      300 was observed in this spectrum, corresponding to a minimum detectable
      absorption of approximately 2 x 10(-9) cm(-1). Comparison with previous
      measurements by use of a conventional FT technique shows that this method gives
      absorption spectra with highly accurate line positions along with reasonable line
      intensities. Investigation of the evolution of intracavity laser absorption
      spectra with the generation time is also shown to be possible with a continuous
      scan FT spectrometer by use of the interleave rapid-scan method.

PMID- 18345129
TI  - Evaluation of the Solutions for two Design Problems Presented at the 1998 Optical
      Interference Coatings Conference.
AB  - Two problems were proposed at the 1998 Conference on Optical Interference
      Coatings: dual-band antireflection coatings and bandpass filters. In excess of 40
      solutions were submitted. An evaluation of those solutions is presented.

PMID- 18345130
TI  - Monte carlo diffusion hybrid model for photon migration in a two-layer turbid
      medium in the frequency domain.
AB  - We propose a hybrid Monte Carlo (MC) diffusion model for calculating the
      spatially resolved reflectance amplitude and phase delay resulting from an
      intensity-modulated pencil beam vertically incident on a two-layer turbid medium.
      The model combines the accuracy of MC at radial distances near the incident beam
      with the computational efficiency afforded by a diffusion calculation at further
      distances. This results in a single forward calculation several hundred times
      faster than pure MC, depending primarily on model parameters. Model predictions
      are compared with MC data for two cases that span the extremes of physiologically
      relevant optical properties: skin overlying fat and skin overlying muscle, both
      in the presence of an exogenous absorber. It is shown that good agreement can be
      achieved for radial distances from 0.5 to 20 mm in both cases. However, in the
      skin-on-muscle case the choice of model parameters and the definition of the
      diffusion coefficient can lead to some interesting discrepancies.

PMID- 18345131
TI  - Optical Properties of Ag-TiO(2) Nanocermet Films Prepared by Cosputtering and
      Multilayer Deposition Techniques.
AB  - Ag-TiO(2) nanocermet thin films, deposited for optical filtering applications by
      two sputtering techniques, codeposition and multilayer deposition, exhibit
      surface plasmon absorption in the spectral range 450-500 nm. The cosputtering
      technique induces a columnar growth, whereas multilayer deposition produces a
      more-random distribution of silver inclusions. Both films have large, flat silver
      grains at the air-cermet interface. An optical double-heterogeneous layer model
      based on the experimental morphological parameters of the films accounts well for
      their experimental transmittance, notably for extra absorption near 700 nm, which
      is attributed to a surface plasmon in the flat silver grains of the surface.

PMID- 18345132
TI  - Birefringence measurement in double-clad fiber lasers with large cross section.
AB  - We report on birefringence measurements in double-clad fibers with large cross
      section, doped with neodymium and ytterbium. The experimental results for
      rectangular double-clad fibers are compared with those for single-clad circular
      neodymium-doped fibers, taking into account existing models of stress- and
      geometry-induced birefringence. We demonstrated that the ellipticity of an outer
      silica cladding has no effect on birefringence in large-area double-clad fibers.
      The stress-induced birefringence is shown to depend on the ratio between the
      diameter of an internal silica support and the linear dimensions of the
      rectangular outer cladding. The stress-distribution pattern is derived to prove
      the experimental results.

PMID- 18345133
TI  - Design of efficient all-optical code-division multiplexing systems supporting
      multiple-bit-rate and equal-bit-rate transmissions.
AB  - We present the design of efficient all-optical code-division multiplexing (AOCDM)
      systems that can transmit multiple-bit-rate (MBR) data signals over a common
      optical fiber. This is achieved when the proposed strict optical orthogonal code
      (OOC) of autocorrelation and cross-correlation constraints of 1 are used but
      without performance degradation compared with the use of conventional OOC. We
      describe the design of various strict OOC's by employing the useful concept of
      slot distances, and methods of code construction are also presented. Moreover, we
      give the principle of MBR data transmissions in an AOCDM system. It is shown that
      AOCDM systems using the proposed OOC can effectively transmit multiuser MBR and
      equal-bit-rate (EBR) data with no increase of system complexity. In principle,
      optimal strict OOC's need the same or a slightly larger system bandwidth compared
      with optimal conventional OOC's for EBR operation, whereas the former can require
      a smaller system bandwidth and have a better system performance than the latter
      for MBR transmissions. A new, to our knowledge, family of strict OOC's is also
      introduced, whose code words can have nonconstant weights to support multiuser
      communications with different transmission quality. Furthermore, we design low
      cost AOCDM transmitters that are based on an efficient gain-switching scheme that
      does not require an electro-optic intensity modulator to on-off modulate an
      optical clock pulse stream at each transmitter. The basic operation principle is
      also experimentally demonstrated.

PMID- 18345134
TI  - Spatial-phase code-division multiple-access system with multiplexed Fourier
      holography switching for reconfigurable optical interconnection.
AB  - A new, to our knowledge, space-variant optical interconnection system based on a
      spatial-phase code-division multiple-access technique with multiplexed Fourier
      holography is described. In this technique a signal beam is spread over wide
      spatial frequencies by an M-sequence pseudorandom phase code. At a receiver side
      a selected signal beam is properly decoded, and at the same time its spatial
      pattern is shaped with a Fourier hologram, which is recorded by light that is
      encoded with the same M-sequence phase mask as the desired signal beam and by
      light whose spatial beam pattern is shaped to a signal routing pattern. Using the
      multiplexed holography, we can simultaneously route multisignal flows into
      individually specified receiver elements. The routing pattern can also be varied
      by means of switching the encoding phase code or replacing the hologram. We
      demonstrated a proof-of-principle experiment with a doubly multiplexed hologram
      that enables simultaneous routing of two signal beams. Using a numerical model,
      we showed that the proposed scheme can manage more than 250 routing patterns for
      one signal flow with one multiplexed hologram at a signal-to-noise ratio of ~5.

PMID- 18345135
TI  - Organic photorefractive glass with infrared sensitivity and fast response.
AB  - Infrared imaging materials with high speed and dynamic range are required for a
      variety of imaging and diagnostic techniques. We present an organic
      photorefractive glass that shows high diffraction efficiencies of as great as 40%
      with 25-mum-thick samples and fast response times of 4.3 ms under irradiation at
      790 nm. Furthermore, the intensity dependence and field dependence of the grating
      decay are investigated.

PMID- 18345136
TI  - Superresolution of binary images with a nonlinear interpolative neural network.
AB  - Superresolution is the process by which the bandwidth of a diffraction-limited
      spectrum is extended beyond the optical passband. Many algorithms exist that are
      capable of superresolution; however, most are iterative methods, which are ill
      suited for real-time operation. One approach that has been virtually ignored is
      the neural-network approach. We consider the feedforward architecture known as a
      multilayer perceptron and present results on simulated binary images blurred by a
      diffraction-limited, circular-aperture optical transfer function and sampled at
      the Nyquist rate. To avoid aliasing, the network performs as a nonlinear spatial
      interpolator while simultaneously extrapolating in the frequency domain.

PMID- 18345137
TI  - Hilbert transform and mirror-image optical correlators.
AB  - An optical correlator, believed to be novel, adds an x-y mirror image to the
      input and filter images to perform convolution involving amplitude and phase. The
      resulting real Fourier transform filters can be loaded into a liquid-crystal
      device (LCD). In contrast, a complex filter would require high-resolution film. A
      Hilbert transform and a point source are applied at the filter plane to reduce
      filter storage and LCD loading time by a factor of 2. An optional spatial filter
      removes an offset intensity and squares the result. Filters have only twice the
      number of pixels of the images. Analysis is verified by computer simulation, and
      performance is discussed.

PMID- 18345138
TI  - Interpolated spatially variant apodization in synthetic aperture radar imagery.
AB  - The original formulation of spatially variant apodization for complex synthetic
      aperture radar imagery concentrated on integer-oversampled data. Noninteger
      oversampled data presented previously [IEEE Trans. Aerosp. Electron. Syst. 31,
      267 (1995)] suggested use of different weightings in the algorithm. An
      alternative noninteger-oversampled approach that employs the same apodization
      concept but uses local spatial interpolation is presented. With this approach the
      combined image formation, apodization, and detection of 1.3x-versus-2.0x
      oversampled data can be performed in half the time without loss of image quality.

PMID- 18345139
TI  - Optoelectronic information encryption with phase-shifting interferometry.
AB  - A technique that combines the high speed and the high security of optical
      encryption with the advantages of electronic transmission, storage, and
      decryption is introduced. Digital phase-shifting interferometry is used for
      efficient recording of phase and amplitude information with an intensity
      recording device. The encryption is performed by use of two random phase codes,
      one in the object plane and another in the Fresnel domain, providing high
      security in the encrypted image and a key with many degrees of freedom. We
      describe how our technique can be adapted to encrypt either the Fraunhofer or the
      Fresnel diffraction pattern of the input. Electronic decryption can be performed
      with a one-step fast Fourier transform reconstruction procedure. Experimental
      results for both systems including a lensless setup are shown.

PMID- 18345140
TI  - High focal depth with a quasi-bifocus birefringent lens.
AB  - The Strehl definition along the axis of a birefringent lens sandwiched between
      two polarizers is studied analytically. The optic axis of the birefringent lens
      made of a uniaxial crystal is perpendicular to the lens axis, and the system
      behaves like a bifocus lens for proper orientation of the polarizers. The Sparrow
      criterion is employed for designing an imaging system with high depth of focus.
      It is shown that, when the two foci are separated by the Sparrow limit of
      resolution, the focal depth is maximum and the intensity point-spread function
      remains almost identical within this limit. The resolution according to the
      Rayleigh criterion in this zone is more than that of an ideal lens.

PMID- 18345141
TI  - Phase measurements with wide-aperture interferometers.
AB  - An interferogram produced by wide-aperture interferometers is studied both
      theoretically and experimentally. The fringe spacing is shown to increase
      nonlinearly with the numerical aperture and the fringe envelope to become
      narrower as the numerical aperture is increased. Phase measurements with wide
      aperture interferometers therefore require calibration, and the phase can be
      measured only over a limited range. A calibration is given for accurate phase
      measurements, and the range over which the phase can be measured is calculated.
      Experimental measurements are presented and compared with theory.

PMID- 18345142
TI  - Tunable electro-optic microlens array. I. Planar geometry.
AB  - A description is given of a microlens array design, believed to be new, with
      tunable focal length. Converging or diverging periodic refractive-index
      distribution is induced in a linear electro-optic wafer through the application
      of electric field profiles on both sides of the wafer. The transparent electrodes
      on both sides of the wafer are positioned such that the electrodes on the
      opposite side compensate the phase delay from the electrodes on the front side of
      the wafer for a normally incident plane wave, suppressing the intrinsic electrode
      diffraction for the device without applied voltage. The original technique of the
      electric field calculation was developed to analyze accurately the induced
      refractive index inside the wafer. Its focal length changes from 7 mm to infinity
      at a 1-mum wavelength with an external voltage range of 0-100 V.

PMID- 18345143
TI  - Stream cipher based on pseudorandom number generation with optical affine
      transformation.
AB  - We propose a new, to our knowledge, stream cipher technique for two-dimensional
      (2-D) image data that can be implemented by iterative optical transformation. The
      stream cipher uses a pseudorandom number generator (PRNG) to generate a
      pseudorandom bit sequence. The proposed method for the PRNG is composed of the
      iterative operation of 2-D affine transformation achieved by optical components
      and by modulo-n addition of the transformed images. We expect efficient execution
      of the method by optical parallel processing. We verify the performance of the
      proposed method in terms of security strength and clarify problems on optical
      implementation by the optical fractal synthesizer.

PMID- 18345144
TI  - Measurement of the thermal conductivity of erasable phase-change optical
      recording media.
AB  - We describe a method to estimate the thermal conductivity of the substrate, the
      dielectric layer, the phase-change (PC) layer, and the reflective layer of PC
      optical recording media. The method relies on the amorphous-to-crystalline phase
      transition that occurs in the PC layer and takes advantage of the difference in
      the thermal diffusion behavior under different-sized focused spots. All the
      results obtained here are reliable with better than ?5% accuracy, which is within
      the margin of our experimental error.

PMID- 18345145
TI  - Effect of film thickness on the performance of photopolymers as holographic
      recording materials.
AB  - An important issue in developing applications for photopolymers in holography is
      the effect of film thickness on recording properties. Now it is possible to
      create these samples with a much wider range of thickness (d = 20-1400 mum) than
      was previously available. We exploit these recent advances in photopolymer
      processing to systematically evaluate how the dynamic range of a photopolymer
      depends on its thickness. The results illustrate that sample performance
      increases linearly with thickness as predicted by standard models of volume
      holography. However, above a critical thickness sample performance degrades, and
      the angular response of recorded plane-wave holograms shows evidence of grating
      curvature. These distortions are likely the result of photopolymer shrinkage,
      which in thicker samples occurs in a nonuniform fashion. This problem limits the
      performance of these photopolymers and is likely to be an issue for any
      photopolymer that undergoes comparable polymerization shrinkage.

PMID- 18345146
TI  - Crystallization and amorphization studies of a Ge(2)Sb(2.3)Te(5) thin-film sample
      under pulsed laser irradiation.
AB  - We present the results of crystallization and amorphization studies on a thin
      film sample of Ge(2)Sb(2.3)Te(5), encapsulated in a quadrilayer stack as in the
      media of phase-change optical disk data storage. The study was conducted on a two
      laser static tester in which one laser, operating in pulsed mode, writes either
      amorphous marks on a crystalline film or crystalline marks on an amorphous film.
      The second laser, operating at low power in the cw mode, simultaneously monitors
      the progress of mark formation in terms of the variations of reflectivity both
      during the write pulse and in the subsequent cooling period. In addition to
      investigating some of the expected features associated with crystallization and
      amorphization, we noted certain curious phenomena during the mark-formation
      process. For example, at low-power pulsed illumination, which is insufficient to
      trigger the phase transition, there is a slight change in the reflectivity of the
      sample. This is believed to be caused by a reversible change in the complex
      refractive index of the Ge(2)Sb(2.3)Te(5) film in the course of heating above the
      ambient temperature. We also observed that the mark-formation process may
      continue for as long as 1 mus beyond the end of the write laser pulse. This
      effect is especially pronounced during amorphous mark formation under high-power,
      long-pulse illumination.

PMID- 18345147
TI  - Differential optical absorption spectroscopy instrument for stratospheric
      balloonborne trace-gas studies.
AB  - A newly developed UV-visible instrument for differential optical absorption
      spectroscopic measurements of atmospheric trace gases from balloon platforms is
      described. Direct solar light at daytime in the near-ultraviolet (320.6-422.6-nm)
      and the visible (417.6-670.7-nm) spectral ranges can be simultaneously analyzed
      for the atmospheric column abundances or profiles of O(3), NO(2), NO(3), BrO,
      OClO, O(4), H(2)O, and possibly other species (HNO(2), IO, CH(2)O). Compared with
      previously used balloonborne UV-visible spectrometers, the instrument has the
      superior properties of low mass (42 kg), low power consumption (30 W), decreased
      spectral drift that is caused by temperature and pressure changes, low detector
      dark current, and low spectrometer stray light. The three last-named
      characteristics are achieved by enclosure of the entire spectrometer in a
      pressurized and thermostated container and by inclusion of separately
      thermostated photodiode array detectors. The optical setup is simplified to
      reduce its weight. The spectral stray light is reduced by suppression of the
      higher-order and zero-order grating reflections by use of light traps and in the
      UV by addition of a dispersive prism preanalyzer. The major instrumental design
      characteristics and the instrumental performance as tested in the laboratory and
      during several stratospheric balloon flights are reported.

PMID- 18345148
TI  - Effect of atmospheric radiance errors in radiometric sea-surface skin temperature
      measurements.
AB  - Errors in measurements of sea-surface skin temperature (SSST) caused by
      inappropriate measurements of sky radiance are discussed; both model simulations
      and in situ data obtained in the Atlantic Ocean are used. These errors are
      typically caused by incorrect radiometer view geometry (pointing), temporal
      mismatches between the sea surface and atmospheric views, and the effect of wind
      on the sea surface. For clear-sky, overcast, or high-humidity atmospheric
      conditions, SSST is relatively insensitive (<0.1 K) to sky-pointing errors of ?10
      degrees and to temporal mismatches between the sea and sky views. In mixed-cloud
      conditions, SSST errors greater than ?0.25 K are possible as a result either of
      poor radiometer pointing or of a temporal mismatch between the sea and sky views.
      Sea-surface emissivity also changes with sea view pointing angle. Sea view
      pointing errors should remain below 5 degrees for SSST errors of <0.1 K. We
      conclude that the clear-sky requirement of satellite infrared SSST observations
      means that sky-pointing errors are small when one is obtaining in situ SSST
      validation data at zenith angles of <40 degrees . At zenith angles greater than
      this, large errors are possible in high-wind-speed conditions. We recommend that
      high-resolution inclinometer measurements always be used, together with regular
      alternating sea and sky views, and that the temporal mismatch between sea and sky
      views be as small as possible. These results have important implications for the
      development of operational autonomous instruments for determining SSST for the
      long-term validation of satellite SSST.

PMID- 18345149
TI  - Lidar measurements taken with a large-aperture liquid mirror. 2. Sodium resonance
      fluorescence system.
AB  - Sodium resonance-fluorescence lidar is an established technique for measuring
      atmospheric composition and dynamics in the mesopause region. A large-power
      aperture product (6.6-W m(2)) sodium resonance-fluorescence lidar has been built
      as a part of the Purple Crow Lidar (PCL) at The University of Western Ontario.
      This sodium resonance-fluorescence lidar measures, with high optical efficiency,
      both sodium density and temperature profiles in the 83-100-km region. The sodium
      lidar operates simultaneously with a powerful Rayleigh- and Raman-scatter lidar
      (66 W m(2)). The PCL is thus capable of simultaneous measurement of temperature
      from the tropopause to the lower thermosphere. The sodium resonance-fluorescence
      lidar is shown to be able to measure temperature to an absolute precision of 1.5
      K and a statistical accuracy of 1 K with a spatial-temporal resolution of 72 (km
      s) at an altitude of 92 km. We present results from three nights of measurements
      taken with the sodium lidar and compare these with coincident Rayleigh-scatter
      lidar measurements. These measurements show significant differences between the
      temperature profiles derived by the two techniques, which we attribute to
      variations in the ratio of molecular nitrogen to molecular oxygen that are not
      accounted for in the standard Rayleigh-scatter temperature analysis.

PMID- 18345150
TI  - Heterodyne lidar returns in the turbulent atmosphere: performance evaluation of
      simulated systems.
AB  - Simulations of beam propagation in three-dimensional random media were used to
      study the effects of atmospheric refractive turbulence on coherent lidar
      performance. By use of the two-beam model, the lidar return is expressed in terms
      of the overlap integral of the transmitter and the virtual (backpropagated) local
      oscillator beams at the target, reducing the problem to one of computing
      irradiance along the two propagation paths. This approach provides the tools for
      analyzing laser radar with general refractive turbulence conditions, beam
      truncation at the antenna aperture, beam-angle misalignment, and arbitrary
      transmitter and receiver configurations. Simplifying assumptions used in
      analytical studies, were tested and treated as benchmarks for determining the
      accuracy of the simulations. The simulation permitted characterization of the
      effect on lidar performance of the analytically intractable return variance that
      results from turbulent fluctuations as well as of the heterodyne optical power
      and system-antenna efficiency.

PMID- 18345151
TI  - Myopic Deconvolution of Adaptive Optics Images by use of Object and Point-Spread
      Function Power Spectra: Comment.
AB  - It is suggested here that the lack of total image correction that is typical in
      adaptive optics (AO) imaging can be attributed in part to blur derived from small
      angle scatter of light by aerosols, known also as the adjacency effect,
      especially as it is a well-established fact that such atmospheric blur is
      dominant in satellite imagery and the shape of the modulation transfer function
      after AO correction is strikingly similar to the unique shape of the aerosol
      modulation transfer function. Further investigation of AO systems to confirm this
      would aid in and improve image restoration.

PMID- 18345152
TI  - Myopic deconvolution of adaptive optics images by use of object and point-spread
      function power spectra: reply to comment.
AB  - Partial correction in adaptive optics (AO) is well understood now. This partial
      correction is due to the limitations of the AO system performance, which leaves
      residual phase fluctuations in the instrument pupil. Knowledge of these residuals
      allows the optical transfer function (OTF) of the high-angular-resolution imaging
      system to be estimated accurately. Therefore, light scattering by aerosols cannot
      be invoked to justify the shape of an AO partial-correction OTF in astronomical
      conditions. The light scattering does not modify the high-angular-resolution OTF
      but merely contributes to a slight increase of the sky background.

PMID- 18345153
TI  - Comparison of Lasing Performance of Tm, Ho:YLF Lasers by use of Single and Double
      Cavities.
AB  - The lasing performance of single-cavity and double-cavity Tm, Ho:YLF lasers was
      measured experimentally. The maximum, single-longitudinal mode output power for
      the double-cavity laser was 30 mW, whereas for the single-cavity laser it was 7
      mW. We determined the frequency stabilities to be 600 Hz for a single-cavity
      laser and 300 Hz for a double-cavity laser, by measuring the fluctuation of a
      self-heterodyne beat signal for a 1.5-micros delay time over a 10-min integrated
      period. In addition, we obtained a 15-GHz frequency tuning range for the double
      cavity laser by changing its cavity length under maximum stable conditions at
      room temperature.

PMID- 18345154
TI  - Generation of terawatt pulses by use of optical parametric chirped pulse
      amplification.
AB  - Optical parametric chirped pulse amplifiers offer exciting prospects for
      generating new extremes in power, intensity, and pulse duration. An experiment is
      described that was used to investigate the operation of this scheme up to
      energies approaching a joule, as a step toward its implementation at the petawatt
      level. The results demonstrate an energy gain of 10(10) with an energy extraction
      efficiency of 20% and close to diffraction-limited performance. Some spectral
      narrowing during amplification was shown to be compatible with the time-varying
      profile of the pump beam and consistent with the measured recompressed pulse
      durations of 260 and 300 fs before and after amplification, respectively.

PMID- 18345155
TI  - Monoblock laser for a low-cost, eyesafe, microlaser range finder.
AB  - A small, lightweight, low-cost prototype laser has been developed for use in a
      microlaser range finder (muLRF). The laser design is based on a flash-lamp
      pumped, Nd:YAG laser with a Cr(4+) passive Q switch. The design incorporates a
      monolithic potassium titanyl arsenide (KTA) optical parametric oscillator (OPO)
      in an intracavity configuration, producing output at 1.54 mum. Precisely cut,
      properly coated crystals make up the laser resonator, reducing the number of
      components and enabling laser oscillation with the simplest of alignment
      fixtures. The 1.54-mum laser cavity consists of only four rectangular-shaped
      crystals: a Nd:YAG laser rod, a Nd:YAG endcap, a Cr(4+) Q switch, and a KTA OPO.
      Along with a ceramic laser pallet and a flash lamp, these six components make up
      a prototype monoblock (essentially a one-piece) laser transmitter. Several of
      these simple prototypes have been built and tested, giving a nominal output of
      >3.0 mJ at 1.54 mum with a 27-ns pulse width. The transmitter was incorporated
      into a breadboard laser range finder, and successful ranging operations were
      performed to targets at ranges in excess of 3 km.

PMID- 18345156
TI  - Quasi-Resonant Nonlinear Absorption for Optical Power Limiting: solgel-Processed
      Er(3+)-Doped Multicomponent Silica Glass.
AB  - We demonstrate optical power limiting by what we believe to be a new mechanism of
      nonlinear absorption, which involves a quasi-resonant ground-state absorption
      that is either phonon assisted or assisted by the presence of defect sites (tail
      absorption). Such a mechanism provides high transmittance at low intensity yet
      optical limiting under cw conditions. The sample used was a novel solgel
      processed Er(3+)-doped multicomponent silica glass. In this system the nonlinear
      absorption process is achieved because the resonant excited-state ((4)I(13/2) ?
      (4)S(3/2)) absorption cross section is larger than the quasi-resonant ground
      state ((4)I(15/2) ? (4)I(9/2)) absorption cross section.

PMID- 18345157
TI  - Two-Photon Absorbing Properties of Ultraviolet Phase-Matchable Crystals at 264
      and 211 nm.
AB  - We investigated the intensity-dependent loss properties of nonlinear crystals by
      using subpicosecond laser pulses at 264 and 211 nm. Two-photon absorption
      coefficients for potassium dihydrogen phosphate, beta-barium borate, and lithium
      triborate crystals were obtained from the intensity-dependent transmission
      measurements.

PMID- 18345158
TI  - Four-Element Receiver for Pulsed 10-mum Heterodyne Doppler Lidar.
AB  - A four-element photomixer receiver has been tested in a 10-mum heterodyne Doppler
      lidar. It addresses a reduction of the variance of the power scattered off
      distributed aerosols targets at ranges as long as 8 km. An improvement in
      performance is expected when the four independent signals recorded on every
      single shot are combined. Two summation techniques of the four signals have been
      implemented: a coherent summation of signal amplitude and an incoherent summation
      of intensities. A phasing technique for the four signals is proposed. It is based
      on a more suitable correlation time with discernible self-consistent packets
      (SCP's). The SCP technique has been successfully tested, and the results obtained
      with a coherent summation of the four signals, i.e., variance reduction, carrier
      to-noise ratio improvement, and velocity accuracy improvement, are in agreement
      with theory.

PMID- 18345159
TI  - Mars orbiter laser altimeter: receiver model and performance analysis.
AB  - The design, calibration, and performance of the Mars Orbiter Laser Altimeter
      (MOLA) receiver are described. The MOLA measurements include the range to the
      surface, which is determined by the laser-pulse time of flight; the height
      variability within the footprint determined by the laser echo pulse width; and
      the apparent surface reflectivity determined by the ratio of the echo to
      transmitted pulse energies.

PMID- 18345160
TI  - Remote-sensing infrared thermometer with radiation balancing.
AB  - What is to our knowledge a novel infrared thermometer (IRT) for remote
      measurement of the temperature rise (-20-100 K) above the variable ambient (270
      320 K) of a distant object is described. A radiation-balancing method is
      successfully extended to the near-ambient temperature range by variation of the
      temperature of a built-in blackbody, until the radiation from it equals the
      radiation from the source, so that its temperature is proportional to that of the
      source. Another feature believed to be novel is simplifying the design by
      elimination of the need for cooling the blackbody for subambient temperature
      range by use of a second blackbody, strategically located, which is heated to
      achieve radiation balance. Detailed theoretical analysis is given, showing that
      the IRT can measure remotely the total emissivity or even the electric current or
      voltage. Resistive inserts are proposed for improving the accuracy of current
      measurement. A method is proposed for simultaneous remote measurement of absolute
      temperature and emissivity by variation of the heating current and the aperture
      of the blackbody for radiation balancing in two bands so that prior knowledge of
      the object's emissivity is not needed.

PMID- 18345161
TI  - Retrieval of chlorophyll from remote-sensing reflectance in the china seas.
AB  - The East China Sea is a typical case 2 water environment, where concentrations of
      phytoplankton pigments, suspended matter, and chromophoric dissolved organic
      matter (CDOM) are all higher than those in the open oceans, because of the
      discharge from the Yangtze River and the Yellow River. By using a hyperspectral
      semianalytical model, we simulated a set of remote-sensing reflectance for a
      variety of chlorophyll, suspended matter, and CDOM concentrations. From this
      simulated data set, a new algorithm for the retrieval of chlorophyll
      concentration from remote-sensing reflectance is proposed. For this method, we
      took into account the 682-nm spectral channel in addition to the Sea-viewing Wide
      Field-of-view Sensor (SeaWiFS) channels. When this algorithm was applied to a
      field data set, the chlorophyll concentrations retrieved through the new
      algorithm were consistent with field measurements to within a small error of 18%,
      in contrast with that of 147% between the SeaWiFS ocean chlorophyll 2 algorithm
      and the in situ observation.

PMID- 18345162
TI  - Narrow-linewidth vertical-cavity surface-emitting lasers for oxygen detection.
AB  - The use of vertical-cavity surface-emitting lasers (VCSEL's) for optical
      detection of atmospheric oxygen is described. The VCSEL's were custom designed
      for single-mode emission in the 763-nm wavelength range, with low noise and
      narrow optical linewidth. Using standard wavelength modulation spectroscopy and a
      second-harmonic detection scheme with a 1-m air path, we determined an oxygen
      concentration resolution of 0.2%. Because of its small size, low power
      dissipation, and good tunability characteristics, the VCSEL promises to be an
      attractive light source for use in compact, low-cost optical sensor microsystems
      for trace gas detection.

PMID- 18345163
TI  - Development of a cavity ringdown laser absorption spectrometer for detection of
      trace levels of mercury.
AB  - A potential new laser-based air pollution measurement technique, capable of
      measuring ultralow concentrations of urban air toxins in the field and in real
      time, is examined. Cavity ringdown laser absorption spectroscopy (CRLAS) holds
      promise as an air pollution monitor because it is a highly sensitive species
      detection technique that uses either pulsed or continuous tunable laser sources.
      The sensitivity results from an extremely long absorption path length and the
      fact that the quantity measured, the cavity decay time, is unaffected by
      fluctuations in the laser source. In laboratory experiments, we reach detection
      limits for mercury of the order of 0.50 parts per trillion. We developed a CRLAS
      system in our laboratory and measured Hg with the system, investigating issues
      such as background interference. We report experimental results for mercury
      detection limits, the dynamic range of the sensor, detection of Hg in an
      absorbing background of ozone and SO(2), and detection of a mercury-containing
      compound (HgCl(2) in this case).

PMID- 18345164
TI  - Spectral Differentiation of Trace Concentrations of NO(2) from NO by Laser
      Photofragmentation with Fragment Ionization at 226 and 452 nm: Quantitative
      Analysis of NO-NO(2) Mixtures.
AB  - Laser-induced photofragmentation with fragment ionization is used to detect and
      spectrally differentiate trace concentrations of NO(2) from NO in NO-NO(2)
      mixtures. A laser operating near 226 or 452 nm ionizes the target molecules, and
      the resulting electrons are collected with miniature electrodes. NO is detected
      by (1 + 1) resonance-enhanced multiphoton ionization by means of its A (2)?(+) ?
      X (2)? (0, 0) transitions near 226 nm, whereas NO(2) is detected near 226 nm by
      laser photofragmentation with subsequent NO fragment ionization by means of both
      its A (2)?(+) ? X (2)? (0, 0) and (1, 1) transitions. The NO fragment generated
      from the photolysis of NO(2) is produced rovibrationally excited with a
      significant population in the first vibrational level of the ground electronic
      state (X (2)?, upsilon? = 1). In contrast, ambient NO has a room-temperature,
      Boltzmann population distribution favoring the lowest ground vibrational level (X
      (2)?, upsilon? = 0). Thus discrimination is possible when the internal energy
      distributions of both fragment NO and ambient NO are probed. We also demonstrate
      this approach using visible radiation, further simplifying the experimental
      apparatus because frequency doubling of the laser radiation is not required. We
      measured up to three decades of NO-NO(2) mixtures with limits of detection
      (signal-to-noise ratio of 3) in the low parts per billion for both NO and NO(2)
      for a 10-s integration time using both ultraviolet or visible radiation.

PMID- 18345165
TI  - Insect thin films as sun blocks, not solar collectors.
AB  - We measured the visible reflectance spectra of whole wing sections from three
      species of iridescent butterflies and moths, for normal incidence, integrated
      over all reflected angles. In this manner, we separated the optics of the thin
      films causing the iridescence from the optics of the rest of the scale. We found
      that iridescence reduces solar absorption by the wing in all cases, typically by
      approximately 20% or less, in contrast to claims by Miaoulis and Heilman [Ann.
      Entomol. Soc. Am. 91, 122 (1998)] that the thin-film structures that produce
      iridescence act as solar collectors.

PMID- 18345166
TI  - Waveguide photodegradation of nonlinear optical organic chromophores in polymeric
      films.
AB  - Waveguide photodegradation studies have been carried out to investigate the
      photostabilities of a series of nonlinear optical chromophores doped into
      poly(methyl methacrylate) waveguide films. The films were exposed to optical
      wavelengths lying either within these materials' main absorption bands or in the
      near-infrared region. Degradation studies were carried out in air, vacuum, and
      nitrogen environments at room temperature. Experimental results indicate that the
      principal photodegradation mechanism in operation is photo-oxidation. A simple
      analytical model indicated the relative sensitivity to photo-oxidation of the
      materials studied.

PMID- 18345167
TI  - Adaptive optics: wave-front correction by use of adaptive filtering and control.
AB  - A class of adaptive-optics problems is described in which phase distortions
      caused by atmospheric turbulence are corrected by adaptive wave-front
      reconstruction with a deformable mirror, i.e., the control loop that drives the
      mirror adapts in real time to time-varying atmospheric conditions, as opposed to
      the linear time-invariant control loops used in conventional adaptive optics. The
      basic problem is posed as an adaptive disturbance-rejection problem with many
      channels. The solution given is an adaptive feedforward control loop built around
      a multichannel adaptive lattice filter. Simulation results are presented for a 1
      m telescope with both one-layer and two-layer atmospheric turbulence profiles.
      These results demonstrate the significant improvement in imaging resolution
      produced by the adaptive control loop compared with a classical linear time
      invariant control loop.

PMID- 18345168
TI  - Diffracted-ray approach to the fast evaluation of diffractive lenses.
AB  - We employ a combination of asymptotic methods to speed up the computation of
      fields in the focal region of a diffractive lens (DL). The DL is treated locally
      as a linear grating with a slowly varying period and groove orientation. We
      employ rigorous electromagnetic diffraction theory locally to obtain the field
      just behind the DL. A simple diffracted-ray formula is derived for the field in
      the focal region of the DL at observation points that are not in the immediate
      vicinity of the optical axis. A careful study of the range of validity of this
      formula is made. For observation points that are not in the immediate vicinity of
      the optical axis the new algorithm is 3 x 10(5) times faster than the application
      of numerical integration to the double integrals involved and approximately 1000
      1200 times faster than a recently published algorithm based on using asymptotic
      theory to replace the double integral with a single integral.

PMID- 18345169
TI  - Optical effect of diffractive multifocal focusing of radiation on a bicomponent
      diffraction system.
AB  - It is shown for the first time, to our knowledge, that when a plane wave
      illuminates a certain type of bicomponent optical system, consisting of two plane
      screens with circular apertures on a given optical axis, a multifocal diffractive
      focusing effect can appear. Here the diffraction picture in the focal planes
      represents the circular nonlocal bands of the Fresnel zones with a bright narrow
      peak at the center, whose intensity can exceed by 6-10 times the value of the
      incident-wave intensity. The detected optical effect is observed across a wide
      range of wavelengths, lambda = 0.4-10(3) microm, and ratios of the aperture
      diameters d(1) >or= 2d(2) = 25-1000 lambda, and it is also insensitive to changes
      in the medium of the wave propagation. For the large diameters of input holes,
      d(1) = 2d(2) > 100 lambda, or for wavelengths in the radio-frequency region of
      the spectrum, the bicomponent diffraction system acts as a long-focus lens with a
      high-intensity Gaussian distribution of radiation, at times exceeding the initial
      intensity, persisting at large distances (z = 1-100 cm) from the diffraction
      system.

PMID- 18345170
TI  - Design and tolerancing of achromatic and anastigmatic diffractive-refractive lens
      systems compared with equivalent conventional lens systems.
AB  - Since focal diffractive optics have been introduced, designing them has
      flourished, particularly as the manufacturing technology has developed to meet
      the performance requirements. My purpose is to introduce to hybrid diffractive
      refractive optical systems not only the design procedure but also the optical and
      the mechanical aspects of optical tolerancing. A comparison is made with
      equivalent conventional (purely refractive) systems in the visible wave band
      (rather than the infrared wave band where there are many published designs) to
      seek advantages and disadvantages that systems with diffractive optics bring. The
      results of tolerancing comparisons show that for small-field systems the
      introduction of diffractive components has a powerful desensitizing effect,
      whereas for a wide-field anastigmatic system that has been investigated the
      desensitization effect of the inclusion of diffractive surfaces is less marked.
      These results come mainly from the fact that an achromatizing diffractive surface
      has little focal power, whereas an achromatizing refractive component has to have
      a large focal power.

PMID- 18345171
TI  - Interference between stretched and original pulses.
AB  - An off-axis holographic recording method for fast-moving objects that has a time
      resolution of several picoseconds and a large depth of field is suggested. Two
      different but mutually coherent laser pulses, the original pulse (20 ps) and a
      stretched pulse (60 ps), are interfered. The short pulse determines the
      resolution, and the stretched pulse increases the field depth. Interference
      patterns between the short and the expanded pulses, for lambda = 1.064 microm and
      lambda = 0.532 microm, are demonstrated.

PMID- 18345172
TI  - TV shearography: quantitative measurement of shear-magnitude fields by use of
      digital speckle photography.
AB  - Digital speckle photography combined with TV shearography is developed for
      precise measurement of the magnitude of the shear field in a linear shear
      configuration. As an application the method is implemented to determine the slope
      change variations of a three-dimensional object with TV shearography in which the
      shear magnitude is obtained with the digital speckle photography technique.

PMID- 18345173
TI  - Edge location by use of optical phase variation.
AB  - Traditional optical methods for locating an edge are based on light intensity
      variation with respect to a reference triggering level. Since the intensity
      variation is subject to stray light, the intensity variation of the light source,
      and the triggering level variation, the exact position of the edge cannot be
      determined. We describe a method for edge location that uses a phase variation in
      a modified differential interferometer. The maximal point of the slope of the
      phase variation across an edge is determined exactly by the relative position
      between the focused beam spot and the detected edge if the initial intensity
      ratio of the two single-frequency interference beams is kept unchanged. Therefore
      the phase variation can be used to locate the edge with high resolution and
      accuracy. To make practical use of the phase variation, the second derivative of
      the phase was used as a monotonic zero-crossing signal across the edge. The
      theoretical and the experimental verification have been conducted in detail. The
      results of the experiment show the feasibility of edge location when phase
      variation is used. The scheme is not affected by stray light and the intensity
      variation of the light source.

PMID- 18345174
TI  - Simultaneous measurement of pure curvature and twist distribution fields by a
      five-aperture shearing and two-fourier filtering technique.
AB  - A five-aperture shearing and two-Fourier filtering technique to measure
      simultaneously pure curvature and twist distribution fields of a deformed object
      is proposed. In this method the slope fringes that are contained in the patterns
      of curvature and twist fringes can be completely eliminated. Thus patterns of
      pure curvature and twist fringes with a good contrast can be obtained. A
      theoretical analysis and experimental results are given.

PMID- 18345175
TI  - Gap measurement by position-sensitive detectors.
AB  - A system for measuring the gap in a proximity exposure tool of a plasma display
      panel (PDP) is developed that uses single or dual position-sensitive detectors
      (PSD's). The resolution of the gap distance is 0.5 mum, with a capture range of
      500 mum. Signal processing is simple and fast and easy because analogous PSD's
      are used as the position sensors. One PSD is used to detect the position of the
      reference beam, which is reflected from the upper surface of the gap; the other
      PSD is used to detect the position of the signal beam, which is reflected from
      the lower surface of the gap. A charge-coupled-device sensor is also employed to
      monitor the reflected beams and the region of measurement. In the gap-measurement
      system that uses a single PSD, first the reference beam is incident upon the PSD
      and then the signal beam is incident upon the same PSD. Then the separation
      between the two beams is calculated from the position of the reference beam and
      from the average beam position.

PMID- 18345176
TI  - Image-based bidirectional reflectance distribution function measurement.
AB  - We present a new image-based process for measuring a surface's bidirectional
      reflectance rapidly, completely, and accurately. Requiring only two cameras, a
      light source, and a test sample of known shape, our method generates densely
      spaced samples covering a large domain of illumination and reflection directions.
      We verified our measurements both by tests of internal consistency and by
      comparison against measurements made with a gonioreflectometer. The resulting
      data show accuracy rivaling that of custom-built dedicated instruments.

PMID- 18345177
TI  - Precision synchronous polarimeter with linear response for the measurement of
      small rotation angles.
AB  - A synchronous polarimeter was set up for the measurement of small rotation angles
      of the polarization plane of light. The polarimeter is based on a polarizer
      Faraday modulator-analyzer structure with a synchronous detection scheme, which
      produces a linear system response. The theoretical background is studied, and the
      system performance is investigated experimentally. We achieved an accuracy of the
      order of 10(-4) deg, or 5 mg/dl of glucose in a 1-cm light path.

PMID- 18345178
TI  - Nontranslational three-dimensional profilometry by chromatic confocal microscopy
      with dynamically configurable micromirror scanning.
AB  - A confocal microscope profilometer, which incorporates chromatic depth scanning
      with a diffractive optical element and a digital micromirror device for
      configurable transverse scanning, provides three-dimensional (3D) quantitative
      measurements without mechanical translation of either the sample or the
      microscope. We used a microscope with various objective lenses (e.g., 40x, 60x,
      and 100x) to achieve different system characteristics. With a 100x objective, the
      microscope acquires stable measurements over a 320 microm x 240 microm surface
      area with a depth resolution of 0.39 microm at a 3-Hz scan rate. The total
      longitudinal field of view is 26.4 microm for a wavelength tuning range of 48.3
      nm. The FWHM value of the longitudinal point-spread function is measured to be
      0.99 microm. We present 3D measurements of a four-phase-level diffractive element
      and an integrated-circuit chip. The resolution and the accuracy are shown to be
      equivalent to those found with use of conventional mechanical scanning.

PMID- 18345179
TI  - Asymmetric white-pupil collimators for high-resolution spectrographs.
AB  - We present the optical principle of a white-pupil collimator made up of two
      mirrors with unequal focal lengths. Analytic formulas for third-order aberrations
      are derived and compared with the results of ray-tracing experiments. It is shown
      that the image quality is good if the second mirror has a suitable conic
      coefficient and the F ratio is not too small. Furthermore, third-order coma and
      astigmatism can be zeroed simultaneously if the angles are also appropriately
      selected. When implemented in high-resolution echelle spectrographs, this design
      permits smaller cross dispersers and cameras, with considerable savings in cost.

PMID- 18345180
TI  - Adaptive systems in speckle-pattern interferometry.
AB  - The concept of adaptivity in television holography is discussed, and various
      realizations of adaptivity are presented. In one possible variation, functions of
      the components of the optical arrangement may be changed to adapt them to
      measurement conditions. An additional peculiarity of the technique is that
      reference waves are produced by holographically reconstructed virtual images. A
      method, believed to be new, is introduced for synthesizing the phase front of the
      master object beam that is produced by a simple holographic optical element and
      is used as a smooth or a speckled reference beam in the electronic speckle
      pattern interferometer. An adaptive interferometer is presented as a measuring
      device for various measuring tasks. Selected applications are shown,
      demonstrating different aspects of adaptivity.

PMID- 18345181
TI  - Phase evaluation of speckle patterns during continuous deformation by use of
      phase-shifting speckle interferometry.
AB  - A method for measurement of continuous displacements that uses phase-shifting
      speckle interferometry is presented. The initial random phase of the speckle
      pattern is evaluated by phase shifting before deformation. The changing phase
      thereafter is evaluated from only one image at a time by a least-squares
      algorithm. The technique can be used for measuring transients and other dynamic
      events, heat expansion as well as other phenomena, for which it is difficult to
      accomplish phase shifting during deformation. Theory along with computer
      simulations and experimental results are described.

PMID- 18345182
TI  - Generation of carrier fringes in holography and shearography.
AB  - Double-exposure holography and double-exposure shearography are often used
      together with the carrier fringe technique, which requires additional shifting of
      the light source in a prescribed manner between exposures. In the holographic
      carrier fringe technique, difficulty in prescribing a suitable movement of the
      light source may be alleviated through visualization of the moire fringes that
      are reconstructed by slight displacement of two overlaid families of ellipsoids
      in a holodiagram. Because shearography is the first differential of holography,
      it is often impractical to perform two successive optical differentiations on the
      ellipsoids to visualize the shearographic carrier fringes. A simple method of
      discerning holographic and shearographic carrier fringes is described. The method
      is based on the hyperboloids in a holodiagram that represent Young's
      (interference) fringes produced by the interference of two point sources. The
      hyperboloids are analogous to holographic carrier fringes, whereas the moire
      patterns reconstructed from two overlaid hyperboloids are analogous to
      shearographic carrier fringes. Use of this method for explaining the formation of
      deformation fringes in plate bending, as well as the effect of light-source
      movement on the deformation fringes, is also illustrated.

PMID- 18345183
TI  - Real-time displacement measurement with a two-wavelength sinusoidal phase
      modulating laser diode interferometer.
AB  - A two-wavelength interferometer that uses two separate modulating currents with
      different phases but the same frequencies to detect a greater degree of object
      displacement in real time is proposed and demonstrated. The measurement error was
      57 nm, roughly 1/80 of the synthetic wavelength. We have confirmed that this
      modulating technique enables us to equip our prototype interferometer with a
      simple feedback-control system that eliminates external disturbance.

PMID- 18345184
TI  - Influence of unparallel grating planes in talbot interferometry with cross
      gratings of different spatial frequencies in two directions.
AB  - The effects of an arbitrary small inclination between two cross gratings on the
      moire fringes in Talbot interferometry are discussed when the frequencies of the
      grating differ in two perpendicular directions. We show that the small angles,
      alpha and beta, by which the beam-splitter cross grating is rotated around the
      two axes parallel to the two perpendicular line directions of the cross grating,
      have a greater influence on the moire fringes with cross gratings than that with
      one-dimensional gratings. A simple and practical detection method for the angles
      between the two unparallel grating planes in Talbot interferometry is also
      proposed. The theoretical analyses are proved by experimental results.

PMID- 18345185
TI  - Measurement of transparent plates with wavelength-tuned phase-shifting
      interferometry.
AB  - A wavelength-tuned Fizeau interferometer is applied to the problem of flatness
      testing of transparent plates. When the plate is positioned at a specific
      distance from the reference surface and an integer-math 13-frame phase-shifting
      algorithm is applied, the system directly filters out unwanted interference
      arising from backsurface reflections. The resulting front-surface profile
      exhibits less than 2 nm of residual error attributable to spurious reflections
      from within the plate.

PMID- 18345186
TI  - Programmable array microscopy with a ferroelectric liquid-crystal spatial light
      modulator.
AB  - We present a programmable array microscope that uses a ferroelectric liquid
      crystal spatial light modulator (SLM) for dynamic generation of scanning
      apertures. A single SLM serves as both the source and the detector aperture array
      in a double-pass confocal system. Successive aperture frames scan the array
      across the viewing area for complete imaging of a sample while preserving depth
      discrimination. Integration of the microscope output across all aperture frames
      produces a confocal image.

PMID- 18345187
TI  - Null-screen testing of fast convex aspheric surfaces.
AB  - A method for null-testing fast convex aspheric optical surfaces is presented. The
      method consists of using a cylindrical screen with a set of lines drawn on it in
      such a way that its image, which is formed by reflection on a perfect surface,
      yields a perfect square grid. Departures from this geometry are due to
      imperfections of the surface, allowing one to know if the surface is close to the
      design shape. Tests conducted with a full hemisphere and with the parabolic
      surface of a lens show the feasibility of the method. Numerical simulations show
      that it is possible to detect surface departures as small as 5 microm.

PMID- 18345188
TI  - Design and evaluation of a null lens for testing the optical performance of
      silicone intraocular lenses.
AB  - A two-element null lens, optimized for a 20-diopter silicone intraocular lens
      (IOL), was designed and tested. The performance of the null lens was examined for
      silicone IOL's with in situ powers from 16 to 24 diopters. Improvements in
      resolution, resolution efficiency, and modulation transfer function were obtained
      over the tested power range.

PMID- 18345189
TI  - Improved design for stray-light reduction with a hemispherical imager.
AB  - We present a significant design improvement over previous visible-light stray
      background-reducing baffles suitable for use on a stabilized deep-space platform.
      In earlier research we showed that when background-light sources are confined to
      a hemisphere or less, a conventional labyrinth baffle can be replaced by an array
      of concentric vanes, oriented away from the desired field of view. This
      configuration delivers substantial savings in size and weight. The present
      improvement replaces the concentric vanes by a smooth curved surface. This
      permits simplified fabrication and handling, provides even more weight reduction,
      and delivers improved performance for a given size. Laboratory measurements
      confirm stray-light performance with approximately 10(-14) rejection viewing as
      close as 3 degrees to a bright-light source.

PMID- 18345190
TI  - Design and manufacture of a gradient-index axicon.
AB  - A gradient-index axicon with its initial focus offset from the back surface was
      designed with the thin-lens approximation. Two samples were fabricated by means
      of the time-varying boundary condition diffusion method, which is based on the
      modified quasi-chemical diffusion model. Intensity profile measurements were
      taken along the focal region of the axicons. The samples produced extended line
      foci. From the intensity measurements, the central spot widths and back focal
      lengths were determined. The peak widths matched theoretical predictions made
      with the diffraction theory for the samples and showed good agreement with the
      predicted widths for a pseudo-Bessel beam, showing that the axicon produced a
      pseudo-diffractionless beam.

PMID- 18345191
TI  - Singular polarization eigenstates in anisotropic stratified structures.
AB  - A new optical element that displays singular polarization eigenstates is
      proposed. It consists of a planar stratified structure composed of alternate
      gyrotropic and birefringent layers. The orthogonality of the polarization
      eigenstates is lost because of anisotropic reflections at the interfaces, which
      are enhanced by the special condition chosen for the multiple-beam interference.
      First we show that the anisotropic reflection at the interface between the layers
      with linear and circular symmetries does produce strong enough dichroism to break
      the orthogonality of polarization eigenstates. Second, we investigate the
      behavior of these eigenstates with respect to their linearity and orthogonality
      as a function of the width of the layers. Our results concretely demonstrate that
      it is possible to control the effective optical parameters of such stratified
      structures by adjusting the thickness of each anisotropic layer. Finally, we
      obtain the necessary conditions for designing a double-layer system with singular
      eigenstates of linear polarization.

PMID- 18345192
TI  - Modeling and measurements of atomic surface roughness.
AB  - We present a geometrical model of atomic topography with which to obtain a
      quantitative assessment of surface roughness. A series of two- and three
      dimensional atomic surface roughness equations with sufficiently realistic
      parameters is developed to permit quantitative comparison with scanning-tunneling
      microscope and atomic-force microscope (AFM) experimental results. The model is
      sufficiently simple that one can easily use it to interpret experimental data.
      Tables are provided with estimated values for two- and three-dimensional rms
      atomic surface roughness in pure metal crystals and ionic crystals based on the
      atomic surface roughness equations. We use these roughness equations to determine
      the roughness of cleaved muscovite mica [essentially, KAl(2)(OH)(2)Si(3)AlO(10)];
      the calculated values for both two- and three-dimensional roughness are
      consistent with those obtained in our AFM measurements. In addition, we
      demonstrate both theoretically and experimentally that atomic surface roughness
      is never zero.

PMID- 18345193
TI  - Effect of local microroughness on the gloss uniformity of printed paper surfaces.
AB  - A critical factor that affects the appearance of printed paper surfaces is gloss
      uniformity, which is usually assessed visually. To relate gloss uniformity to
      nonvisual quantities, we first visually identified areas of either high or low
      gloss on the same sample for two different types of paper. We then measured the
      roughness and the reflectance of these areas. Microroughness was measured with an
      atomic-force microscope, and roughness was measured over a larger area with a
      confocal laser scanning microscope. The local reflectance of the high-gloss and
      the low-gloss areas was obtained from images taken with a gloss-imaging
      instrument and compared with the roughness of each area. This correlation is
      nonlinear, and roughness is insufficient to predict the local reflectance. Light
      scattering measurements were made in the specular direction to map the gloss
      uniformity over larger areas than was possible with the gloss-imaging instrument.
      These maps were used to show the possibility of using both the spatial frequency
      and the fan filters, which together form a set of cortex filters, to analyze the
      variation of the gloss about the mean value and its spatial distribution on the
      surface in terms of spatial frequency and azimuthal orientation.

PMID- 18345194
TI  - Unified analytical inversion of reflectometric and ellipsometric data of
      absorbing media.
AB  - We present a unified two-step analytical inversion of reflectometric and
      ellipsometric data of absorbing media. Instead of a direct determination of the
      optical constants n, kappa from reflectometric or ellipsometric measurements, we
      first calculate the real and the imaginary part eta, gamma of the normal
      component of the wave vector in the absorbing medium. New and simple analytical
      formulas are obtained for eta and gamma in terms of rho(s), rho(p) or tan psi,
      delta, respectively, where rho(s), rho(p) and tan psi, delta are the measured
      reflectometric and ellipsometric parameters of the absorbing medium. The optical
      constants are then easily determined analytically again from eta, gamma. We use
      the new formulas to compare the sensitivity with experimental errors due to the
      inversion of reflectometric and ellipsometric data.

PMID- 18345195
TI  - Measurement of refractive-index change at a liquid-solid interface close to the
      critical angle.
AB  - We measured the refractive-index change on a liquid sample, using the reflection
      of a polarized Gaussian laser beam close to the angle of total reflection. We
      applied this technique to a solution of nickel (ii) phthalocyanine
      tetrasulfonated (NiPTS) in water-ethanol (1/1 v/v), in which the nonlinearity of
      the refractive index is due to optically induced thermal effects. We show that
      close to the angle of total reflection the sensitivity of this technique is four
      times bigger than at normal incidence.

PMID- 18345196
TI  - Test of opticlean strip coating material for removing surface contamination.
AB  - The strip coating material, Opticlean, which has been reformulated, has been
      shown to remove 1-5-microm-diameter particles as well as contamination remaining
      from previous drag wipe cleaning on a used silicon wafer. In addition, no residue
      that produced scattering was found on a fresh silicon wafer when Opticlean was
      applied and then stripped off. The total integrated scattering technique used for
      the measurements could measure scattering levels of He-Ne laser light as low as a
      few ppm (parts in 10(6)), corresponding to a surface roughness of <1 A rms.

PMID- 18345197
TI  - Some comments on the paper by Edward S. Fry on the visible and near-ultraviolet
      absorption spectrum of liquid water.
AB  - It is contended that the most comprehensive collection of data on the visible and
      near-ultraviolet spectrum of pure liquid water can still be found [Appl. Opt. 38,
      1216 (1999)]. The data produced [Appl. Opt. 36, 8710 (1997)] from the integrated
      light loss in a light-scattering cavity containing water produces a useful set of
      data, although the error bars presented are underestimated. Furthermore, an
      oxidative purification step was not incorporated into the water purification
      procedure to remove residual traces of light-absorbing organic impurities.

PMID- 18345198
TI  - Visible and near-ultraviolet absorption spectrum of liquid water: comment.
AB  - Measurements of the absorption of pure water have been described [Appl. Opt. 38,
      1216 (1999)]. This comment on that paper disputes the claims that (1) their list
      of references on pure water absorption is complete, (2) their result "...provides
      reliable data in the 320-420-nm region...," and (3) their data agree well with
      existing data in the literature. The clearest demonstration of these points is
      made by plotting their data and its associated error bars together with plots of
      other data in the literature that should be considered significantly more
      reliable. Finally, for practical applications that require absorption data, a
      suggestion is made for the best choice of absorption coefficients in the range of
      196 nm <or= lambda <or= 700 nm.

PMID- 18345199
TI  - Optical properties of Ag -TiO 2 nanocermet films prepared by cosputtering and
      multilayer deposition techniques.
AB  - Ag -TiO2 nanocermet thin films, deposited for optical filtering applications by
      two sputtering techniques, codeposition and multilayer deposition, exhibit
      surface plasmon absorption in the spectral range 450 -500 nm. The cosputtering
      technique induces a columnar growth, whereas multilayer deposition produces a
      more-random distribution of silver inclusions. Both films have large, flat silver
      grains at the air -cermet interface. An optical double-heterogeneous layer model
      based on the experimental morphological parameters of the films accounts well for
      their experimental transmittance, notably for extra absorption near 700 nm, which
      is attributed to a surface plasmon in the flat silver grains of the surface.

PMID- 18345200
TI  - High-performance thin-film polarizing beam splitter operating at angles greater
      than the critical angle.
AB  - A new type of thin-film polarizing beam splitter (PBS) is proposed that is based
      on the effects of light interference and frustrated total internal reflection.
      This PBS has a significantly better performance than conventional thin-film
      PBS's. It is nonabsorbing, broadband, and wide angle and has high extinction
      ratios in both the transmitted and the reflected beams. The principles and theory
      of this PBS are described in detail. Several PBS's designed for the visible and
      the infrared spectral regions are described. The measured results for a prototype
      visible PBS of this type are presented as well.

PMID- 18345201
TI  - Reflectance measurements and optical constants in the extreme ultraviolet for
      thin films of ion-beam-deposited SiC, Mo, Mg2Si, and InSb and of evaporated Cr.
AB  - Reflectance measurements and optical constants of thin films of ion-beam
      deposited SiC, Mo, Mg(2)Si, and InSb and of evaporated Cr have been measured in
      the extreme-ultraviolet (EUV) spectral region from 49.0 to 200.0 nm. In this
      spectral region no optical constant data were available for materials deposited
      by ion-beam deposition. We compared our data with those for bulk samples and for
      thin films prepared by different techniques. The goal of this research has been
      to study candidate materials for multilayer coatings in the EUV.

PMID- 18345202
TI  - Optical performance of the 6.5-m off-axis new planetary telescope.
AB  - We describe an off-axis design for a 6.5-m astronomical telescope optimized for
      low scattered light and low emissivity. This is part of a new concept for an
      instrument that we call the New Planetary Telescope. We show how the geometric
      optical performance can equal that of an on-axis conventional telescope while the
      diffractive performance fundamentally surpasses conventional telescopes because
      of the absence of pupil obstruction. The decentered concept also allows wide
      field and versatile instrumentation configurations that are not possible with
      more-conventional designs.

PMID- 18345203
TI  - Medium-precision null-screen testing of off-axis parabolic mirrors for segmented
      primary telescope optics: the large millimeter telescope.
AB  - The feasibility of using null screens for testing the segments of a parabolic
      segmented telescope mirror for the Large Millimeter Telescope (LMT) is analyzed.
      An algorithm for designing the null screen for testing the off-axis segments of
      conic surfaces is described. Actual screen designs for the different classes of
      segments of the LMT are presented. The sensitivity of the test and the required
      accuracies for the fabrication and positioning of the screen are analyzed. A
      measuring accuracy of approximately 12 microm in surface sagitta is within the
      reach of the technique.

PMID- 18345204
TI  - Aplanatic corrector designs for the extremely large telescope.
AB  - The next century is knocking on our door, bringing with it the possibility of
      telescopes even bigger than the 8-10-m-class instruments that have proliferated
      over the past decade. The fixed spherical reflector is the most economical and
      pragmatic way to construct an extremely large primary mirror (30-50 m in
      diameter). Although spherical mirrors have virtues such as manufacturability and
      identically figured segments, they also create great amounts of spherical
      aberration and coma. Here we show that there are several catoptric (all
      reflecting) corrector designs that enable a fast telescope based on a spherical
      primary mirror.

PMID- 18345205
TI  - Laboratory facilities and recommendations for the characterization of biological
      ultraviolet dosimeters.
AB  - A laboratory facility for characterizing biological dosimeters for the
      measurement of UV radiation has been built and tested. The facility is based on a
      solar simulator, stabilized by photofeedback, and monitored by a
      spectroradiometer, with a versatile filter arrangement. This enables the
      following characteristics of the dosimeters to be ascertained: spectral response,
      linearity, and reciprocity; angular acceptance and response; calibration in
      simulated sunlight. The system has been tested on a variety of dosimeters and has
      the potential to be used with other radiometers, subject currently to the size of
      their active surface.

PMID- 18345206
TI  - Blood-flow measurements with a small number of scattering events.
AB  - Results of simulations of the diffraction of a laser beam by a small blood vessel
      imbedded in scattering tissue are presented. The form of the spectra of
      biospeckle intensity fluctuations is analyzed. The Doppler shift of intensity
      fluctuations of scattered light is investigated as a function of the laser beam
      radius, the radius of the blood vessel, the depth of the vessel in the tissue,
      and the scattering characteristics of flowing blood. A formula that serves as the
      basis for a method of absolute measurements of blood-flow velocity is derived.

PMID- 18345207
TI  - Effects of fluorescence excitation geometry on the accuracy of DNA fragment
      sizing by flow cytometry.
AB  - We report on various excitation geometries used in ultrasensitive flow cytometry
      that yield a linear relation between the fluorescence intensity measured from
      individual stained DNA fragments and the lengths of the fragments (in base
      pairs). This linearity holds for DNA samples that exhibit a wide range of
      conformations. The variety of DNA conformations leads to a distribution of dipole
      moment orientations for the dye molecules intercalated into the DNA. It is
      consequently important to use an excitation geometry such that all dye molecules
      are detected with similar efficiency. To estimate the conformation and the extent
      of elongation of the stained fragments in the flow, fluorescence polarization
      anisotropy and autocorrelation measurements were performed. Significant extension
      was observed for DNA fragments under the flow conditions frequently used for DNA
      fragment sizing. Classical calculations of the fluorescence emission collected
      over a finite solid angle are in agreement with the experimental measurements and
      have confirmed the relative insensitivity to DNA conformation of an orthogonal
      excitation geometry. Furthermore, the calculations suggested a modified
      excitation geometry that has increased our sizing resolution.

PMID- 18345208
TI  - Inclusion characterization in a scattering slab with time-resolved transmittance
      measurements: perturbation analysis.
AB  - A procedure for the time-domain optical characterization of an inclusion in a
      scattering slab is investigated theoretically and experimentally. The method
      relies on the measurement of a contrast function, which is defined as the time
      dependent relative change in the transmitted signal resulting from the presence
      of the inclusion. Analytical expressions for the contrast functions of absorptive
      and diffusive inclusions are obtained through a perturbation solution of the
      diffusion equation. This procedure is used successfully to determine the optical
      properties of absorptive, diffusive, and mixed inclusions located at midplane in
      a scattering slab by use of time-resolved transmittance measurements.

PMID- 18345209
TI  - Pulsed digital holography for deformation measurements on biological tissues.
AB  - Digital holograms are recorded of biological tissues by use of a Q-switched
      double-pulsed ruby laser. An image-plane digital holography setup is used with a
      CCD camera for capturing two holograms with a short time separation (20-800
      micros). Subtraction of the phase distribution in two digital holograms yield a
      fringe phase map that shows the change in deformation of the tissue surface
      between the recordings. Experiments are performed on tissue from a pig that was
      excited by a short-shock pulse and on a human hand that was excited by sinusoidal
      stimulation. Results when the object is imaged through an endoscope are also
      presented. The technique could be an approach for measuring parameters like
      elasticity on biological tissues.

PMID- 18345210
TI  - Optical Doppler velocimetry at various retinal vessel depths by variation of the
      source coherence length.
AB  - We report on what we believe is a novel approach to measuring the velocity of red
      blood cells (RBC's) at different depths of retinal vessels by use of low
      coherence sources. The technique, variable coherence optical Doppler velocimetry
      (VCODV), performs Doppler shift measurements through autodyne mixing between the
      light scattered by the RBC's and by the vessel front wall (reference). Only the
      light from RBC's moving at a depth less than half the coherence length (CL) mixes
      efficiently with the reference. Measurements of the Doppler shifts from RBC's
      with sources of four different CL's in a 152-microm vein of a volunteer confirmed
      the feasibility of VCODV. This approach has the potential to monitor in vivo
      retinal RBC velocity gradient at the vessel wall and the velocity profile within
      the blood vessel in the condition of symmetric blood flow profiles.

PMID- 18345211
TI  - Three-dimensional analysis of subwavelength diffractive optical elements with the
      finite-difference time-domain method.
AB  - We present a three-dimensional (3D) analysis of subwavelength diffractive optical
      elements (DOE's), using the finite-difference time-domain (FDTD) method. To this
      end we develop and apply efficient 3D FDTD methods that exploit DOE properties,
      such as symmetry. An axisymmetric method is validated experimentally and is used
      to validate the more general 3D method. Analyses of subwavelength gratings and
      lenses, both with and without rotational symmetry, are presented in addition to a
      2 x 2 subwavelength focusing array generator.

PMID- 18345212
TI  - Study of an ultrafast analog-to-digital conversion scheme based on diffractive
      optics.
AB  - A potentially ultrafast optical analog-to-digital (A/D) converter scheme is
      proposed and was partly studied experimentally. In the A/D converter scheme the
      input signal controls the wavelength of a diode laser, whose output beam is
      incident on a grating. The beam from the grating hits a diffractive optical
      element in an array. The wavelength determines which element is illuminated. Each
      element fans out a unique spot-pattern bit code to be read out in parallel by
      individual detectors. In the experiment all patterns but one from 64 array
      elements were read out correctly.

PMID- 18345213
TI  - Visualization of surface acoustic waves by means of synchronous amplitude
      modulated illumination.
AB  - A simple technique for visualizing two-dimensional traveling surface acoustic
      wave (SAW) phenomena in real time was developed. The technique requires
      illumination of a SAW carrying substrate with a collimated, sinusoidally
      amplitude-modulated laser beam. Though at first the technique may appear to be
      stroboscopic in nature, it in fact has its foundations in spatiotemporal
      correlation theory. It is shown that if the modulation frequency of the
      illumination beam is equal to, or an integer fraction of, the SAW frequency
      (i.e., if they are temporally correlated) then, after simple spatial filtering,
      high-visibility stationary fringes can be produced. In fact, it is shown that a
      maximum fringe visibility of nearly 60% can be achieved. It is believed that this
      is the highest visibility yet reported for similar SAW visualization techniques.

PMID- 18345214
TI  - Error dependence of quantized kinoform reconstruction on the position of the
      desired image.
AB  - Two-dimensional Fourier transform kinoforms can be calculated by use of a
      discrete Fourier transform. It is well known that the off-axis reconstruction has
      lower reconstruction error than the on-axis one. Here we make what to our
      knowledge is a new analysis on the effect of phase quantization in the Fourier
      domain. We find that the kinoform reconstruction error changes periodically
      according to the position of the desired image when a large dummy area is added.
      The error dependence of quantized kinoform reconstruction is simulated on the
      position of the desired image by use of the iterative dummy area method and the
      iterative interlacing technique.

PMID- 18345215
TI  - Image reconstructions in diffraction tomography from limited transmitted field
      data sets.
AB  - Diffraction tomography reconstructions of objects from limited transmitted field
      data sets are discussed together with theoretical analyses and results of
      numerical experiments. It is shown that limited data sets, representing only a
      small part of the complete data sets, can be used for reconstructions in
      diffraction tomography with satisfactory accuracy. We also find that, in
      diffraction tomography based on the hybrid filtered backpropagation and the first
      Rytov approximation, the use of limited data sets can provide a larger range of
      validity than the use of complete data sets, the reason being that limited data
      sets pose less-severe phase-unwrapping problems.

PMID- 18345216
TI  - Optical realization of the ambiguity function of real two-dimensional light
      sources.
AB  - We propose a setup that can generate the sectional ambiguity function of a two
      dimensional real light source. The setup is easy to implement; the theoretical
      analysis and experimental results are given.

PMID- 18345217
TI  - Intraclass and between-class training-image registration for correlation-filter
      synthesis.
AB  - Correlation filters have traditionally been designed without much attention given
      to the issue of the training images within a class or the relative spatial
      position between classes. We examine the impact of training-set registration on
      correlation-filter performance and develop techniques for centering the training
      images from a class that result in improved performance. We also show that it is
      beneficial to adjust the spatial position of the classes relative to one another.
      Although the proposed techniques are relevant for many types of correlation
      filter, we limit our discussion to algorithms for the maximum average correlation
      height filter and the distance classifier correlation filter.

PMID- 18345218
TI  - Real-time edge-enhanced optical correlation with a cerium-doped potassium sodium
      strontium barium niobate photorefractive crystal.
AB  - The nonlinear diffraction property of a volume grating written by two-wave mixing
      in a cerium-doped potassium sodium strontium barium niobate crystal is applied in
      a coherent image processing system to obtain real-time image edge enhancement as
      well as edge-enhanced optical correlation. The theoretical analysis of the
      correlator is given, and the experimental results of optical correlation are
      presented, which are compared with the computer-simulated results.

PMID- 18345219
TI  - Separation of isoclinics and isochromatics from photoelastic data with a
      regularized phase-tracking technique.
AB  - We present the application of a regularization algorithm to the processing of
      photoelastic fringe patterns. The method used is a modified regularized phase
      tracking (RPT) algorithm applied to phase-shifted images. In particular, we
      present an algorithm for isoclinic-isochromatic separation that uses only five
      images. In the case of isoclinics the method can deal with problems associated
      with modulation of isochromatics and with isotropic points by means of a modified
      cost functional. With respect to the isochromatics the problems associated with
      regions of high fringe density are solved in a robust way by the unmodified RPT
      algorithm by use of the modulation information. The performance of the method is
      discussed, and experimental results are presented.

PMID- 18345220
TI  - At-wavelength, system-level flare characterization of extreme-ultraviolet optical
      systems.
AB  - The extreme-ultraviolet (EUV) phase-shifting point-diffraction interferometer
      (PS/PDI) has recently been developed to provide high-accuracy wave-front
      characterization critical to the development of EUV lithography systems. Here we
      describe an enhanced implementation of the PS/PDI that significantly extends its
      measurement bandwidth. The enhanced PS/PDI is capable of simultaneously
      characterizing both wave front and flare. PS/PDI-based flare characterization of
      two recently fabricated EUV 10x-reduction lithographic optical systems is
      presented.

PMID- 18345221
TI  - Model-based resolution: applying the theory in quantitative microscopy.
AB  - Model-based image processing techniques have been proposed as a way to increase
      the resolution of optical microscopes. Here a model based on the microscope's
      point-spread function is analyzed, and the resolution limits achieved with a
      proposed goodness-of-fit criterion are quantified. Several experiments were
      performed to evaluate the possibilities and limitations of this method: (a)
      experiments with an ideal (diffraction-limited) microscope, (b) experiments with
      simulated dots and a real microscope, and (c) experiments with real dots acquired
      with a real microscope. The results show that a threefold increase over classical
      resolution (e.g., Rayleigh) is possible. These results can be affected by model
      misspecifications, whereas model corruption, as seen in the effect of Poisson
      noise, seems to be unimportant. This research can be considered to be preliminary
      with the final goal being the accurate measurement of various cytogenetic
      properties, such as gene distributions, in labeled preparations.

PMID- 18345222
TI  - Direct control of fractal pattern generation on an optical fractal synthesizer.
AB  - We propose a method for direct control of position, rotation, and scaling of
      fractal patterns generated on an optical fractal synthesizer. In this method we
      introduce an iterated-function-system mother function to produce control
      parameters for arbitrary fractal patterns. We implemented the method
      experimentally and verified the effectiveness of the method.

PMID- 18345223
TI  - Topologies for optical interconnection networks based on the optical transpose
      interconnection system.
AB  - Many results exist in the literature describing technological and theoretical
      advances in optical network topologies and design. However, an essential effort
      has yet to be made in linking those results together. We propose a step in this
      direction by giving optical layouts for several graph-theoretical topologies
      studied in the literature, using the optical transpose interconnection system
      (OTIS) architecture. These topologies include the family of partitioned optical
      passive star (POPS) and stack-Kautz networks as well as a generalization of the
      Kautz and the de Bruijn digraphs.

PMID- 18345224
TI  - Secure ultrafast communication with spatial-temporal converters.
AB  - An encrypted database interfaced with an ultrafast secure data communication
      system using spatial-temporal converters is proposed. The original spatial signal
      is optically encrypted, and the encrypted signal is holographically stored in a
      storage medium such as photorefractive materials. The spatially encrypted signal
      is sampled to avoid the overlap of each datum at the receiver. The sampled data
      are converted into a temporal signal to transmit the information through an
      optical fiber. At the receiver the temporal signal is converted back into the
      spatially encrypted signal. Retrieval of the original data can be achieved when
      the correct phase key is used in the decryption system. We developed an
      expression for encrypted output and decrypted data. We numerically evaluate the
      effect of sampling the spatially encrypted signal on the quality of the decrypted
      data.

PMID- 18345225
TI  - Improvement of terahertz imaging with a dynamic subtraction technique.
AB  - By use of dynamic subtraction it is feasible to adopt phase-sensitive detection
      with a CCD camera to reduce long-term optical background drift. We report on a
      two-order improvement of the signal-to-noise ratio. The improved system is used
      to image terahertz field distribution generated by an optically rectified electro
      optic crystal with a modulation depth as small as 10(-4). We also introduce a
      modified detection geometry that realizes near-field imaging capability with
      greatly improved spatial resolution.

PMID- 18345226
TI  - Estimation of the inherent optical properties of natural waters from the
      irradiance attenuation coefficient and reflectance in the presence of Raman
      scattering.
AB  - By means of radiative transfer simulations we developed a model for estimating
      the absorption a, the scattering b, and the backscattering b(b) coefficients in
      the upper ocean from irradiance reflectance just beneath the sea surface, R(0-),
      and the average attenuation coefficient for downwelling irradiance, <K(d)>1,
      between the surface and the first attenuation depth. The model accounts for Raman
      scattering by water, and it does not require any assumption about the spectral
      shapes of a, b, and b(b). The best estimations are obtained for a and b(b) in the
      blue and green spectral regions, where errors of a few percent to <10% are
      expected over a broad range of chlorophyll concentration in water. The model is
      useful for satellite ocean color applications because the model input, R(0-) and
      <K(d)>1, can be retrieved from remote sensing and the model output, a and b(b),
      is the major determinant of remote-sensing reflectance.

PMID- 18345227
TI  - Irradiance inversion algorithm for estimating the absorption and backscattering
      coefficients of natural waters: Raman-scattering effects.
AB  - We modify an algorithm for retrieving the absorption (a) and backscattering
      (b(b)) coefficient profiles in natural waters by inverting profiles of
      downwelling and upwelling irradiance so as to include the presence of Raman
      scattering. For a given wavelength of interest, lambda, the light field at the
      appropriate Raman excitation wavelength lambda(e) is first inverted to obtain the
      Raman source function at lambda. Starting from estimates of the inherent optical
      properties at lambda, the contribution to the irradiances at lambda from Raman
      scattering is then estimated and subtracted from the total irradiances to obtain
      the elastically scattered irradiances. We then inverted the elastically scattered
      irradiances to find new estimates of a and b(b) using our original method [Appl.
      Opt. 37, 3886 (1998)]. The algorithm then operates iteratively: The new estimates
      are used with the Raman source function to derive a new estimate of the Raman
      contribution, etc. Sample results are provided that demonstrate the working of
      the algorithm and show that the absorption and scattering coefficients can be
      retrieved with accuracies similar to those in the absence of Raman scattering
      down to depths at which the light field is significantly perturbed by it, e.g.,
      with approximately 90% of the upwelling light field originating from Raman
      scattering.

PMID- 18345228
TI  - Numerical simulation of an adaptive optics system with laser propagation in the
      atmosphere.
AB  - A comprehensive model of laser propagation in the atmosphere with a complete
      adaptive optics (AO) system for phase compensation is presented, and a
      corresponding computer program is compiled. A direct wave-front gradient control
      method is used to reconstruct the wave-front phase. With the long-exposure Strehl
      ratio as the evaluation parameter, a numerical simulation of an AO system in a
      stationary state with the atmospheric propagation of a laser beam was conducted.
      It was found that for certain conditions the phase screen that describes
      turbulence in the atmosphere might not be isotropic. Numerical experiments show
      that the computational results in imaging of lenses by means of the fast Fourier
      transform (FFT) method agree well with those computed by means of an integration
      method. However, the computer time required for the FFT method is 1 order of
      magnitude less than that of the integration method. Phase tailoring of the
      calculated phase is presented as a means to solve the problem that variance of
      the calculated residual phase does not correspond to the correction effectiveness
      of an AO system. It is found for the first time to our knowledge that for a
      constant delay time of an AO system, when the lateral wind speed exceeds a
      threshold, the compensation effectiveness of an AO system is better than that of
      complete phase conjugation. This finding indicates that the better compensation
      capability of an AO system does not mean better correction effectiveness.

PMID- 18345229
TI  - Frequency-derived distributed optical-fiber sensing technique: theory and
      characterization.
AB  - Frequency-derived distributed optical-fiber sensing is a method for remote
      measurement of the spatial distribution of linear birefringence in an optical
      fiber, allowing a corresponding measurement of those external measurands that
      influence this birefringence. The method employs a pump-probe scheme, which, by
      use of the optical Kerr effect, generates an optical modulation of the probe
      beam, with a modulation frequency whose temporal variation maps the spatial
      distribution of birefringence. We provide a complete theoretical analysis of this
      method by using Jones calculus and graphic representation on the Poincare sphere.
      The relevant characterization of the technique and some experimental results are
      also presented; these show good agreement with the theory.

PMID- 18345230
TI  - One-way imaging with an aberrated reference beam.
AB  - We demonstrate image reconstruction by way of four-wave mixing for a signal that
      makes a single pass through a distorting medium. Both the signal and the
      reference originate from the same source and propagate through the same
      disturbance. In the four-wave mixing process, phase aberrations are subtracted
      out. A read beam from a second source reconstructs the undistorted image,
      yielding a phase conjugate without a double pass through the disturbance. Good
      reconstructed image fidelity is demonstrated for static distortions if the phase
      mismatch between the signal and the reference beams is minimized. If there is
      significant phase mismatch, reconstructed image fidelity is poor. We show that
      this technique can also be used to measure the autocorrelation function of the
      disturbance when the mismatch between the signal and the reference in the four
      wave mixing scheme is varied.

PMID- 18345231
TI  - Strain-independent temperature measurement by use of a fluorescence intensity
      ratio technique in optical fiber.
AB  - The strain sensitivity of the fluorescence intensity ratio temperature-sensing
      technique has been measured to be (2 +/- 3) x 10(-4)%/muepsilon in Yb3+-doped
      fiber, implying a temperature-to-strain cross sensitivity of (2 +/- 3) x 10(-4)
      degrees C/muepsilon. The near-zero strain sensitivity means that this optical
      fiber sensor technique is well suited for temperature measurement in strain
      affected environments.

PMID- 18345232
TI  - Efficient acousto-optic Q switching of Er:YSGG lasers at 2.79-microm wavelength.
AB  - A flash-lamp-pumped Er:Cr:YSGG laser at 2.79-microm wavelength has been acousto
      optically Q switched. The Q-switched pulse energy and duration depend on pump
      pulse level and relative Q-switching time. Limits of single-pulse operation with
      the given acousto-optic diffraction efficiency have been determined. Resonator
      length, position of the Q switch, and output mirror reflectivity have been varied
      to obtain high pulse energy and the shortest pulse duration in the TEM00
      transverse laser mode. A maximum single-pulse energy of 27 mJ and a minimum pulse
      duration of 120 ns were obtained with an output mirror reflectivity of
      approximately 25%. The highest Q-switched single-pulse energy amounted to 52% of
      the free-running, fundamental mode output pulse energy.

PMID- 18345233
TI  - Theoretical investigation of the optical trapping properties of a micro-optic
      cubic glass structure.
AB  - An enhanced ray optics model is applied to the study of the optical levitation
      and trapping properties of a glass cubic object. It is found that for certain
      highly symmetric orientations simultaneous force and torque equilibrium can exist
      in the lowest-order TEM00 laser beam profile. For analytical purposes, the square
      surfaces of the cube are divided into two identical triangular surfaces, and the
      interaction of the rays with these triangular surfaces simplifies the computation
      of the total force and torque on the cube. The technique developed can easily be
      extended to the study of other regular or complex structures.

PMID- 18345234
TI  - Polygonal optical cavities.
AB  - A general class of multifacet optical resonators that have uniform polygonal
      geometries is described. Expressions for the transmission of light through
      classical refractive escape from the cavities are presented. The conventional
      Fabry-Perot resonator is shown to be a special case of this general class of
      cavities. The effects of absorption and scattering of optical radiation on the
      transmission properties and cavity-quality factors are analyzed. These resonator
      structures have significant applications in a wide variety of optical devices.

PMID- 18345235
TI  - Power scaling and frequency stabilization of an injection-locked Nd:YAG rod
      laser.
AB  - The power scaling and frequency stabilization of a high-power, injection-locked,
      arc-lamp-pumped Nd:YAG laser at 1064 nm are discussed theoretically and
      experimentally. Thermal lensing and induced birefringence at high pump powers are
      modeled, and the effectiveness of the model for compensating thermal lensing is
      demonstrated with four different laser heads. Two distinct active frequency
      stabilization schemes for injection-locked lasers are also compared theoretically
      and experimentally. These efforts yield a 24-W, linearly polarized, continuous
      wave, TEM00 output with a spectral linewidth of 1.5 Hz measured by heterodyne
      detection.

PMID- 18345236
TI  - Tunable extended-cavity diode laser stabilized on iodine at lambda = 633 nm.
AB  - We present a tunable extended-cavity semiconductor laser, based on the Littman
      configuration, which has been frequency-stabilized to Doppler-free hyperfine
      transitions in I2. The stability was measured compared with the reference He-Ne
      I2 laser system, whereas the semiconductor laser was locked on components of the
      P(33) 6-3 transition close enough to the reference R(127) 11-5 line to allow beat
      frequency counting. A relative stability of 4 x 10(-12) over a 100-s integration
      time was achieved. The laser configuration allowed mode-hop-free tuning over a
      range including the P(33) 6-3 transition and the group of strong overlapping
      transitions R(60) 8-4, R(125) 9-4, and P(54) 8-4 with higher signal-to-noise
      ratio than the P(33) 6-3 located approximately 13 GHz toward lower optical
      frequencies.

PMID- 18345237
TI  - Laser beam shaping with polarization-selective diffractive phase elements.
AB  - A new scheme for converting a Gaussian irradiance profile beam on the input plane
      into a uniform irradiance profile beam on the output plane is presented based on
      polarization-selective diffractive phase elements. The relevant elements were
      designed by use of the simulated annealing method. The simulation design shows
      that the shaping quality is substantially improved and is much better than that
      obtained with traditional diffractive phase elements.

PMID- 18345238
TI  - Thermally boosted pumping of neodymium lasers.
AB  - Pumping at 885 nm from thermally excited ground-state levels directly to the
      Nd:YAG upper lasing level is experimentally demonstrated by use of a Ti:sapphire
      pump laser. This approach utilizes thermal energy contained within the laser
      medium to provide part of the pump energy required to achieve population
      inversion. Slope efficiency increased by 12% compared with traditional pump band
      excitation (lambda(pump) = 808 nm) and by 7% compared with ground-state direct
      pumping (lambda(pump) = 869 nm). The combined transition from the first and
      second thermally excited Stark components of the ground state (4I(9/2)) to the
      upper lasing level (4F(3/2)) has characteristics that make thermally boosted
      pumping a suitable candidate for use with diode lasers: reasonable absorption
      (1.8 cm(-1)) and bandwidth (2.7 nm FWHM). A model suggests that, compared with
      traditional 808-nm pumping, heat could be reduced by 40% by use of thermally
      boosted pumping.

PMID- 18345239
TI  - Investigation of damage mechanisms of KTiOPO4 crystals by use of a continuous
      wave argon laser.
AB  - We have developed a simple method that uses cw irradiation from an argon laser to
      measure the damage threshold of KTP crystals. Our experimental results show that
      there are two types of damage in KTP crystal, depending on the polarization of
      the incident laser beam. One type of optical damage is the appearance of gray
      tracks, including both dark tracks and orange dots, when the pump polarization is
      perpendicular to the z axis. The other type is invisible damage when the
      polarization is parallel to the z axis. In addition, we have also observed weak
      photorefractive two-wave mixing in KTP crystals in each of these polarization
      states. After a systematic analysis we have concluded that the first type of
      damage is due to the formation and absorption of Ti3+ and Fe3+ centers and the
      second is due to the drift of K+ ions. The weak photorefractive effect is the
      result of screening of the electric field by the drifted K+ ions.

PMID- 18345240
TI  - Distributed-feedback dye-doped solgel silica lasers.
AB  - Dye-doped solgel silica lasers with distributed feedback were demonstrated.
      Solgel silica slabs doped with Rhodamine 6G or Coumarin 460 dyes were fabricated.
      Periodic gain modulation in dye-doped solgel silica slabs were created by the
      interference pattern of the pumped laser beams diffracted by a holographic
      grating. Laser pulse trains with subnanosecond spikes were induced. Laser
      emission wavelengths were centered at 480 and 585 nm for Rhodamine 6G and
      Coumarin 460, respectively. It was possible for us to tune approximately 20 nm
      around the emission centers by varying the intersection angle. The laser
      linewidth was of the order of 60 pm.

PMID- 18345241
TI  - Effect of spatial hole burning on injection-locked vertical-cavity surface
      emitting laser arrays.
AB  - Injection locking of vertical-cavity surface-emitting laser arrays is analyzed at
      steady state, including the effect of spatial hole burning. A free-running laser
      array (i.e., without injection), that operates well-above threshold, can exhibit
      multimode oscillations. Consequently, each of the free-running modes (at
      different frequencies) needs a different locking injection power. For low pump
      levels, just above threshold, the array is single mode and, as expected, the
      results bear a close resemblance to those of the average gain analysis, which
      ignores spatial hole burning.

PMID- 18345242
TI  - Efficient continuous-wave ultraviolet generation in LiB3O5 and RbD2AsO4.
AB  - We have demonstrated two continuous-wave nonlinear processes: third-harmonic
      generation (THG) of 1064-nm radiation with a lithium triborate (LBO) crystal, and
      second-harmonic generation of 696-nm radiation in deuterated rubidium dihydrogen
      arsenate. With 34 mW of 1064-nm and 25 mW of 532-nm radiation incident upon the
      LBO crystal, as much as 60 nW of third-harmonic power has been produced. We
      present the characteristics that optimize the production of nonlinear power in
      this sum-frequency generation process. In the second experiment, 15 nW of
      radiation at 348 nm was produced with 9 mW of 696-nm incident radiation. Both
      processes will play an important role in the new generation of optical synthesis
      techniques.

PMID- 18345243
TI  - Simulations of the observation of clouds and aerosols with the Experimental Lidar
      in Space Equipment system.
AB  - We carried out a simulation study for the observation of clouds and aerosols with
      the Japanese Experimental Lidar in Space Equipment (ELISE), which is a two
      wavelength backscatter lidar with three detection channels. The National Space
      Development Agency of Japan plans to launch the ELISE on the Mission Demonstrate
      Satellite 2 (MDS-2). In the simulations, the lidar return signals for the ELISE
      are calculated for an artificial, two-dimensional atmospheric model including
      different types of clouds and aerosols. The signal detection processes are
      simulated realistically by inclusion of various sources of noise. The lidar
      signals that are generated are then used as input for simulations of data
      analysis with inversion algorithms to investigate retrieval of the optical
      properties of clouds and aerosols. The results demonstrate that the ELISE can
      provide global data on the structures and optical properties of clouds and
      aerosols. We also conducted an analysis of the effects of cloud inhomogeneity on
      retrievals from averaged lidar profiles. We show that the effects are significant
      for space lidar observations of optically thick broken clouds.

PMID- 18345244
TI  - Displacement measurement that uses transient photoelectromotive force effects in
      CdTe:V with frequency-modulated lasers.
AB  - A new method of displacement measurement that uses the transient
      photoelectromotive force effects that arise in semiconductors illuminated by two
      frequency-modulated lasers is proposed and demonstrated experimentally. A height
      resolution of 0.85 microm was achieved experimentally; theoretical analysis
      charts the path toward eventual improvement of this resolution.

PMID- 18345245
TI  - Multipurpose spectral imager.
AB  - A small spectral imaging system is presented that images static or moving objects
      simultaneously as a function of wavelength. The main physical principle is
      outlined and demonstrated. The instrument is capable of resolving both spectral
      and spatial information from targets throughout the entire visible region. The
      spectral domain has a bandpass of 12 A. One can achieve the spatial domain by
      rotating the system's front mirror with a high-resolution stepper motor. The
      spatial resolution range from millimeters to several meters depends mainly on the
      front optics used and whether the target is fixed (static) or movable relative to
      the instrument. Different applications and examples are explored, including
      outdoor landscapes, industrial fish-related targets, and ground-level objects
      observed in the more traditional way from an airborne carrier (remote sensing).
      Through the examples, we found that the instrument correctly classifies whether a
      shrimp is peeled and whether it can disclose the spectral and spatial
      microcharacteristics of targets such as a fish nematode (parasite). In the
      macroregime, we were able to distinguish a marine vessel from the surrounding sea
      and sky. A study of the directional spectral albedo from clouds, mountains, snow
      cover, and vegetation has also been included. With the airborne experiment, the
      imager successfully classified snow cover, leads, and new and rafted ice, as seen
      from 10.000 ft (3.048 m).

PMID- 18345246
TI  - Doppler-free nonlinear absorption in ethylene by use of continuous-wave cavity
      ringdown spectroscopy.
AB  - We report what we believe to be the first systematic study of Doppler-free,
      nonlinear absorption by use of cavity ringdown spectroscopy. We have developed a
      variant of cavity ringdown spectroscopy for the mid-infrared region between 9 and
      11 microm, exploiting the intracavity power buildup that is possible with
      continuous-wave lasers. The infrared source consists of a continuous-wave CO2
      laser with 1-mW tunable infrared sidebands that couple into a high-finesse stable
      resonator. We tune the sideband frequencies to observe a saturated, Doppler-free
      Lamb dip in the nu7, 11(1,10) <-- 11(2,10) rovibrational transition of ethylene
      (C2H4). Power studies of the Lamb dip are presented to examine the intracavity
      effects of saturation on the Lamb-dip linewidth, the peak depth, and the
      broadband absorption.

PMID- 18345247
TI  - Nonlinear absorption of thin Al2O3 films at 193 nm.
AB  - Absorption of thin Al2O3 films was measured at 193 nm with an ArF-laser
      calorimeter. In addition to the expected high linear absorption coefficient, we
      found, for the first time to our knowledge, that two-photon absorption and
      transient color-center formation are nonnegligible loss channels in thin films at
      193 nm. The nonlinear absorption coefficient is of the order of several times 10(
      4) cm/W.

PMID- 18345248
TI  - Berry fruits as a source of biologically active compounds: the case of Lonicera
      caerulea.
AB  - BACKGROUND: Lonicera caerulea L. (blueberry honeysuckle, Caprifoliaceae) is a
      traditional crop in northern Russia, China, and Japan. Its fruits are little
      known as edible berries in North America and Europe. This review deals with the
      botany and chemical composition of L. caerulea and the biological activity of its
      main constituents, focusing on the potential health benefits of the berries.
      METHODS AND RESULTS: PubMed, Science Direct and ISI Web of Knowledge databases
      were used for this paper. Literature sources include the period 1935-2007. L.
      caerulea berries a are rich source of phenolic compounds such as phenolic acids
      as well as anthocyanins, proanthocyanidins and other flavonoids, which display
      potential health promoting effects. Chemopreventive, antimicrobial, anti
      adherence and antioxidant benefits, among others are described for these
      compounds. CONCLUSIONS: The potential of L. caerulea berries to prevent chronic
      diseases such as diabetes mellitus, cardiovascular diseases and cancer seems to
      be related above all to their phenolic content.

PMID- 18345249
TI  - Biological aspects of Lyme disease spirochetes: unique bacteria of the Borrelia
      burgdorferi species group.
AB  - BACKGROUND: Borrelia burgdorferi sensu lato is a group of at least twelve closely
      related species some of which are responsible for Lyme disease, the most frequent
      zoonosis in Europe and the USA. Many of the biological features of Borrelia are
      unique in prokaryotes and very interesting not only from the medical viewpoint
      but also from the view of molecular biology. METHODS: Relevant recent articles
      were searched using PubMed and Google search tools. RESULTS AND CONCLUSION: This
      is a review of the biological, genetic and physiological features of the
      spirochete species group, Borrelia burgdorferi sensu lato. In spite of a lot of
      recent articles focused on B. burgdorferi sensu lato, many features of Borrelia
      biology remain obscure. It is one of the main reasons for persisting problems
      with prevention, diagnosis and therapy of Lyme disease. The aim of the review is
      to summarize ongoing current knowledge into a lucid and comprehensible form.

PMID- 18345250
TI  - Retinoids, rexinoids and their cognate nuclear receptors: character and their
      role in chemoprevention of selected malignant diseases.
AB  - BACKGROUND: Retinoids, rexinoids and their biologically active derivatives are
      involved in a complex arrangement of physiological and developmental responses in
      many tissues of higher vertebrates. Both retinoids and rexinoids are either
      natural or synthetic compounds related to retinoic acids that act through
      interaction with two basic types of nuclear receptors belonging to the nuclear
      receptor superfamily: All-trans retinoic acid receptors (RARalpha, RARbeta, and
      RARgamma) and retinoid X receptors (RXRalpha, RXRbeta and RXRgamma) as retinoid
      inducible transcription factors. AIM: Summarization of selected effects of
      biologically active natural or synthetic retinoids and rexinoids and their
      exploitation in chemoprevention of various types of cancer. RESULTS: Retinoid
      receptors play a role as ligand-activated, DNA-binding, trans-acting,
      transcription-modulating proteins involved in a general molecular mechanism
      responsible for transcriptional responses in target genes. They exert both
      beneficial and detrimental activity; they have tumour-suppressive activity but on
      the other hand they are teratogenic. A number of nuclear receptor selective
      retinoids and rexinoids, have been successfully tested using a variety of cell
      lines or animal models. Retinoids inhibit carcinogenesis, suppress premalignant
      epithelial lesions and tumour growth and invasion in a variety of tissues.
      CONCLUSIONS: Natural and synthetic retinoids exert important biological effects
      due to their antiproliferative and apoptosis-inducing effects. They are also
      known to cause redifferentiation or to prevent further dedifferentiation of
      various tumour tissues.

PMID- 18345251
TI  - Action of leptin on bone and its relationship to menopause.
AB  - BACKGROUND: Leptin a cytokine protein secreted by adipose tissue raises
      considerable interest as a potential mediator of the protective effects of fat
      mass on bone tissue. After menopause heavier women conserve bone mass better than
      those with lower body weight. The protective effect of obesity on bone mass has
      been ascribed to a high body fat content. As Leptin levels reflect the body fat
      content it has emerged as a possible mediator of these protective effects.
      METHODS: A search of the available literature focused on the role of leptin on
      bone tissue. RESULTS: Both peripheral and central action of leptin on bone
      metabolism have been proposed. In vitro and in vivo evidence supports the
      hypothesis that leptin can act directly or indirectly on bone remodelling by
      modulating both osteoblast and osteoclast activities. However, studies in humans
      have not yet been able to confirm these actions possibly because of the shifting
      balance between stimulatory direct action and suppressive indirect action of
      leptin on bones via the hypothalamus. The effects of oestrogen decline and
      deficiency during natural or artificially induced menopause and administration of
      hormone replacement therapy has on leptin production remains controversial.
      Various studies have shown differences in leptin values in pre- and
      postmenopausal women. The existing clinical data on this issue are discordant.
      CONCLUSION: Larger clinical studies are necessary to clarify leptin's role in
      vivo and to assess the contribution of the central and peripheral role of leptin
      in the overall maintenance of bone turnover in human beings.

PMID- 18345252
TI  - Neurohumoral changes in chronic heart failure.
AB  - BACKGROUND: Humoral systems play an important role in the pathophysiology and
      development of chronic heart failure (CHF). METHODS: We conducted a search of
      neurohumoral activation in heart failure and its risk in the development of CHF.
      RESULTS AND CONCLUSION: Neurohumoral factors may be divided into
      vasoconstrictive, vasodilative and cytokines. The main vasoconstrictive systems
      are the renin-angiotensin-aldosterone system (RAAS) and the sympathoadrenal
      system (SAS). Cytokines include tumour necrosis factor (TNF) alpha and
      interleukins. The systems of actions are interconnected and they mutually
      influence their secretion and activities. The possibilities of their detection
      and assessment for clinical purposes depend on their changes and kinetics in the
      organism and on the activity of individual metabolites. Apart from their
      vasoactive effects, the majority of humoral actions also interfere in the process
      of remodelling, function of the endothelium, blood elements, cardiomyocytes,
      cells of the smooth muscles, and in immunity as well as inflammatory processes.
      The rapid development of knowledge on the humoral actions in recent years has
      made possible their utilisation in diagnostics, treatment and prognosis.

PMID- 18345253
TI  - The role of various modalities in breast imaging.
AB  - BACKGROUND: Breast cancer is the most common type of cancer in women worldwide.
      Mammography is considered the "gold standard" in the evaluation of the breast
      from an imaging perspective. Apart from mammography, ultrasound examination and
      magnetic resonance imaging are being offered as adjuncts to the preoperative
      workup. Recently, other new modalities like positron emission tomography, 99mTc
      sestamibi scintimammography, and electrical impedance tomography (EIT) are also
      being offered. However, there is still controversy over the most appropriate use
      of these new modalities. Based on the literature, this review evaluates the role
      of various modalities used in the screening and diagnosis of breast cancer.
      METHODS AND RESULTS: Based on relevant literatures this article gives an overview
      of the old and new modalities used in the field of breast imaging. A narrative
      literature review of all the relevant papers known to the authors was conducted.
      The search of literatures was done using pubmed and ovid search engines.
      Additional references were found through bibliography reviews of relevant
      articles. It was clear that though various new technics and methods have emerged,
      none have substituted mammography and it is still the only proven screening
      method for the breast as of date. CONCLUSION: From the literature it is clear
      that apropos modern radiology's impact on diagnosis, staging and patient follow
      up, only one imaging technique has had a significant impact on screening
      asymptomatic individuals for cancer i.e.; low-dose mammography. Mammography is
      the only screening test proven in breast imaging. Positron emission tomography
      (PET) also plays an important role in staging breast cancer and monitoring
      treatment response. As imaging techniques improve, the role of imaging will
      continue to evolve with the goal remaining a decrease in breast cancer morbidity
      and mortality. Progress in the development and commercialisation of EIT breast
      imaging system will definitely help to promote other systems and applications
      based on the EIT and similar visualization methods. Breast ultrasound and breast
      magnetic resonance imaging (MRI) are frequently used adjuncts to mammography in
      today's clinical practice and these techniques enhance the radiologist's ability
      to detect cancer and assess disease extent, which is crucial in treatment
      planning and staging.

PMID- 18345254
TI  - Intra-arterial chemotherapy and its significance in the treatment of
      oropharyngeal carcinoma.
AB  - BACKGROUND: In complex therapeutic algorithms for cancer, regional intra-arterial
      chemotherapy is usually used as an adjuvant and placed in the beginning of
      treatment. Clinical experience however shows that the achieved remission of
      malignant tumour illness after non-adjuvant chemotherapy is only temporary and
      short-lived. The illness progresses relatively quickly if the patient receives no
      further treatment and most clinical studies have not found any significant
      increase in life expectancy in oncological patients treated with this method. The
      question remains to what extent the poor results are due to the treatment method
      and its position in the therapeutic algorithm, and to what extent they are due to
      imperfect knowledge of molecular tumour genetics or inappropriate choice of the
      neoadjuvant intra-arterial chemotherapy METHODS: We compared preliminary results
      of immunohistochemical examinations (detection and analysis of expression of
      proteins Ku 70, STAT 1,3,5 which take part in the regulation of cell cycle
      apoptosis and repair of damaged DNA, carried out before and after chemotherapy,
      suggest that depending on the effects of neoadjuvant intra-arterial chemotherapy
      and patient's survivance. RESULTS AND CONCLUSION: An overview of intra-arterial
      neoadjuvant chemotherapy of head and neck is presented. Knowledge of cell cycle
      processes, especially apoptosis and repair of damaged DNA, could significantly
      influence the choice of the therapeutic algorithm and therapeutical effect.

PMID- 18345255
TI  - Physiological effects of different types of beta-glucan.
AB  - BACKGROUND: Numerous types of glucans have been isolated from almost every
      species of yeast, grain, and fungi. These products have been extensively studied
      for their immunological and pharmacological effects. AIM: In this paper we
      evaluated the possibility whether individual glucans will be similarly active
      against each of the tested biological properties or if each glucan will affect
      different reactions. METHODS: Immunological effects of glucans were measured by
      evaluation of phagocytosis of HEMA particles by peripheral blood leukocytes and
      production of IL-2 by mouse splenocytes. Next we measured the effects of long
      term treatment with glucan on levels of blood glucose and blood cholesterol. Four
      different glucans differing in origin (yeast, grain and mushroom) were used.
      RESULTS: Our results showed that the same glucan, yeast-derived insoluble #300
      glucan, stimulated phagocytosis of peripheral blood leukocytes, production of IL
      2 by mouse splenocytes, lowered the cholesterol levels in mice with
      experimentally-induced cholesterolemia and lowered the level of blood sugar after
      induced hyperglycaemie. The remainder of tested glucans were only marginally
      active. CONCLUSION: Taken together, our study showed that with respect to natural
      glucans, there is a yes-or-no effect suggesting that highly purified and highly
      active glucans will have pleiotropic impact, whereas poorly isolated and/or less
      active glucans will have only mediocre biological properties.

PMID- 18345256
TI  - Urinary clusterin concentrations--a possible marker of nephropathy? Pilot study.
AB  - BACKGROUND: Clusterin is a glycoprotein which participates in a number of
      pathophysiological processes in the organism. Information about clusterin use in
      the diagnosis of nephropathy and the differential diagnosis of proteinuria has
      been published recently. AIM: Search for correlations between urinary clusterin
      concentration and other renal function markers. Evaluation of urinary clusterin
      measurement use in the differential diagnosis of nephropathy. METHODS: Urea,
      creatinine, IgG, transferin, Na, K in serum and 24-hour collected urine were
      measured in a sample of 82 individuals. Cystatin C in sera was also measured as
      were GMT, alpha-1 microglobulin, albumin, total protein in urine. In all probands
      urinary clusterin was assayed (ELISA). RESULTS: Urinary clusterin values
      correlated with urinary total protein concentrations (r = 0.28; p = 0.018), total
      protein/creatinine index (r = 0.26; p = 0.02). No correlation was found between
      urine clusterin concentration and glomerular filtration rate, age, urine
      GMT/creatinine, alpha-1-microglobulin, urine albumin and albumin/creatinine ratio
      or Na, K fractional excretions. We found no urinary clusterin differences by sex
      of probands. No evidence of any relationship between urine clusterin and presence
      of defect of renal function, number of risk factors (chi(2) = 16.0; DF = 15; p =
      0.38), albumin/creatinine index (chi(2) = 0.76; DF = 3; p = 0,86), total
      protein/creatinine (chi(2) = 6.5; DF = 3; p = 0.09), GMT/creatinine (chi(2) =
      2.3; DF = 3; p = 0.51), high urinary alpha-1-microglobulin (chi(2) = 4.1; DF = 3;
      p = 0.25) or decreased of GFR (chi(2) = 1.3; DF = 3; p = 0.74). CONCLUSIONS: A
      positive correlation exists between urinary clusterin and urinary total protein
      and total protein/ creatinine index. Urinary clusterin measurement with ELISA
      test does not offer any advantage over routinely used parameters for nephropathy
      diagnosis and the differential diagnosis of proteinuria type.

PMID- 18345257
TI  - mRNA levels of peroxisome proliferator-activated receptors and their coactivators
      are affected by glucose deprivation and oleate in human hepatoma hepG2 cells.
AB  - AIMS: Very modest changes in mRNA stability can affect critical points in
      cellular energy pathways. The aim of this study was to investigate the impact of
      energy abundant substrates on peroxisome proliferator-activated receptors (PPARs)
      and PPAR-gamma coactivators (PGCs) mRNA's steady-state levels. METHODS:
      Quantitative RT-PCR study was performed to assess the effect of zero or normal (5
      mmol/l) glucose and/or oleic acid (0.3 mmol/l) on mRNA levels of (PPARs) (PGCs)
      in HepG2 cells. RESULTS: PGC-1alpha mRNA was significantly upregulated in glucose
      deprived cells (123 % of the control level; p < 0.05), while PGC-1beta mRNA was
      significantly enhanced in oleate-fed cells (134 % and 160 % of control levels for
      zero glucose plus oleate and normal glucose plus oleate, respectively; p < 0.05)
      during the 0.5 h incubation. Upon the 4 h incubation, PPAR-gamma1 and PGC-1alpha
      mRNAs were significantly elevated in cells lacking glucose (142 % and 163 % of
      control levels, respectively; p < 0.05). Oleate significantly suppressed PPAR
      alpha and PGC-1beta mRNA levels in glucose-deprived cells (58 % and 49 % of
      control levels, respectively; p < 0.05). PPAR-gamma1 and -gamma2 mRNAs were
      significantly superinduced when the cells were treated with cycloheximide,
      whereas PPAR-alpha and PGC-1alpha and-1beta mRNAs were destabilized. Upon
      actinomycin D treatment, glucose shortage significantly stabilized PPAR-alpha
      mRNA, while PGC-1alpha mRNA was destabilized by oleate in glucose-deprived cells.
      CONCLUSIONS: Our findings provide evidence that transcriptional processes that
      are under the control of energetic substrates are interconnected with concurrent
      translational processes that can change stability of mRNAs.

PMID- 18345258
TI  - Use of glycogen phosphorylase BB measurement with POCT in the diagnosis of acute
      coronary syndromes. A comparison with the ELISA method.
AB  - BACKGROUND: Glycogen Phosphorylase BB (GPBB) is considered an early and specific
      marker of myocardial necrosis and ischemia. A POCT kit GPBB for diagnostic use
      has recently been approved. AIM: an evaluation of the correspondence of
      qualitative POCT GBPP measurements with ELISA test results. MATERIAL AND
      METHODOLOGY: 20 individuals with non-ST elevation myocardial infarction (non
      STEMI) and 20 probands without acute coronary syndrome (ACS) were tested. GPBB
      (POCT, ELISA) in venous plasma (lithium-heparin) was assayed in all probands.
      RESULTS: individuals with non-STEMI had significantly higher GPBB ELISA values
      (32.3 vs. 6.1 microg/l; p < 0.01). GPBB sensitivity and specificity for non-STEMI
      presence 6 hours after chest pain generation were 100 %. No proband was
      classified in a different subgroup with POCT of GPBB (positive/negative). GPBB
      POCT correlate with a non- STEMI diagnosis (chi(2) 36.1; p <0.01). CONCLUSION:
      GPBB POCT measurement is comparable with ELISA test results. GPBB analysis could
      expand the diagnostic palette in the first hours after the onset of acute
      coronary syndrome.

PMID- 18345259
TI  - Immunohistochemical assessment of E-cadherin and beta-catenin in
      trichofolliculomas and trichoepitheliomas.
AB  - BACKGROUND: Trichofolliculomas and trichoepitheliomas are benign skin neoplasms
      originating from hair follicle cells. They result from defects in the signaling
      pathways that regulate hair follicle morphogenesis and regeneration. Thus they
      seem to be an excellent model of these processes. It is known that the E
      cadherin/beta-catenin system of adhesion molecules plays a crucial role in the
      maintenance of tissue architecture. AIM: The aim of the present study was to
      investigate their involvement in benign hair follicle tumor development. METHODS:
      Semiquantitative intensity of expression were examined in formalin-fixed and
      paraffin-embedded tissue sections of 53 trichoepitheliomas, 15 trichofolliculomas
      and 19 normal skin samples by indirect immunohistochemistry. RESULTS: The
      intensity of E-cadherin/beta-catenin expression in tumor cells did not differ
      from controls. However, normal hair follicles cells exhibited membranous E
      cadherin/beta-catenin expression, whereas both types of tumors, particularly
      trichoepitheliomas, showed E-cadherin/beta-catenin expression with a
      predominantly cytoplasmic localization. CONCLUSIONS: We suggest that this
      dystopic distribution of the E-cadherin/beta-catenin complex in hair follicle
      tumor cells may be a marker of cell-cell adhesion disruption which may contribute
      to the tumor formation.

PMID- 18345260
TI  - Glycaemic index of selected foodstuffs in healthy persons.
AB  - AIMS: The aim of this study was to determine glycaemic index (GI) of 10 popular
      foodstuffs/mixed meals in healthy persons. METHODS: Ten tested foodstuffs and
      glucose standard were consumed in three replicates in the course of a defined 9
      day meal plan: puffed rice squares with chocolate, dark chocolate, white bread,
      honey and glucose for breakfast (at 7 a.m.) and dinner (at 8 p.m.); pasta with
      meat, fried fish with mashed potatoes, and buttered apricot dumplings for lunch
      (at 12 a.m.); wafers, puffed spelt squares with chocolate, and tomato soup for
      snack (at 4 p.m.). Each portion contained 50 g of carbohydrates and was consumed
      within 30 minutes. Glucose concentrations were measured by means of the Continous
      Glucose Monitoring System (CGMS, Medtronic Minimed, Northridge, CA, USA). The
      results were processed by Solutions Software (Medtronic Minimed, Northridge, CA,
      USA) and DegifXL4 software, Palacky University, Olomouc, CZ. Twenty healthy
      persons aged 21.9 +/- 1.39 y (mean +/- SE), BMI 23.6 +/- 0.63 kg/m(2) completed
      the study. RESULTS: GI of tested foodstuffs ranged from 34.7 % (chocolate) to
      105.3 % (puffed rice squares with chocolate). There were more than tenfold
      differences between minimal and maximal values of the GI for some foodstuffs.
      Significant interindividual differences were found between GIs of foodstuffs.
      CONCLUSIONS: In twenty healthy persons the glycaemic indexes of ten popular
      foodstuffs were determined, to be added to the nutritional labels in order to
      facilitate the optimum meal planning.

PMID- 18345261
TI  - Occurence of adverse events due to continuous glucose monitoring.
AB  - AIMS: Continuous glucose monitoring (CGM) using transcutaneous sensors is
      becoming a sophisticated method to control and regulate glucose metabolism. The
      transcutaneous sensor of the CGM system (CGMS Medtronic Minimed, Northridge, CA,
      USA) is chosen to measure glucose concentration in interstitial fluid up to three
      days after insertion even though its function remains stable for a longer period.
      The question arises, which factors really limit the period of sensor insertion
      without unnecessary risk. The aim of this study was to assess any adverse events
      occurring in the course of 9 days after the sensor insertion. METHODS: In a group
      of 22 healthy volunteers aged 21.8+/-1.30 y (mean +/- SE) a total of 26 sensors
      was inserted subcutaneously in gluteal or lumbar region for 9 days. Before
      insertion the site was sprayed with an antiseptic (Cutasept F, Bode Chemie,
      Hamburg, Germany). Local adverse reactions and disturbances in general condition
      were examined. RESULTS: In the course of 184 sensor-days, there were only minor
      local adverse events: hypersensitivity, itching, pain, redness, burning,
      subcutaneous hemorrhage. Additionally, sleep disturbances, attention deficits,
      problems related to the CGMS monitor, to adhesive tape and/or sensor were found.
      None of these resulted in sensor withdrawal. In 12 volunteers (55 %) no
      complications were observed. The sensor function measured according to electrical
      signals (ISIG) failed (always on day 1-2) in 4 cases (16 %). CONCLUSIONS: The
      present FDA approved 3-day insertion period for Medtronic transcutaneous sensor
      does not seem to limit its use and appears to be worth a careful revision.

PMID- 18345262
TI  - Evaluation of transcutaneous bilirubinometry in preterm infants of gestational
      age 32-34 weeks.
AB  - AIMS: The aim of this prospective study was to evaluate the accuracy of
      transcutaneous bilirubinometry using the Minolta Air-Shields JM-103 device in
      preterm newborns of gestational age 32-34 weeks, and to identify the most
      appropriate measurement site. METHODS: Transcutaneous bilirubin (TcB)
      measurements were performed over forehead, sternum and abdomen, if total serum
      bilirubin (TSB) had to be determined on clinical indication in neonates of
      selected gestational age. TSB levels were measured in a clinical laboratory using
      direct spectrophotometry. In order to assess transcutaneous bilirubinometry
      accuracy, differences between TSB and TcB, their CI 95%, and correlation
      coefficients (r) between TcB and TSB were evaluated. RESULTS: The study group
      consisted of 44 infants, including 6 very low birth weight (VLBW) neonates. The
      correlations between transcutaneous and laboratory values were found to be
      significant and close. Minimal differences were observed when measured over
      sternum. The measurements over forehead had a tendency to underestimate TSB
      levels. CONCLUSIONS: Noninvasive measurement by Minolta JM-103 demonstrated
      significant accuracy. The authors recommend measurements over sternum or abdomen
      in premature infants born within 32-34 gestational weeks as a reliable and
      accurate neonatal hyperbilirubinemia screening test. Transcutaneous
      bilirubinometry has the potential to reduce the number of blood samplings, thus
      reducing neonatal pain and discomfort, parental distress and medical care cost.

PMID- 18345263
TI  - A changed view of serum prealbumin in the elderly: prealbumin values influenced
      by concomitant inflammation.
AB  - AIMS: We are currently witnessing changes in views on the evaluation of serum
      proteins. A decrease may signal not only malnutrition. It may also be an
      indicator of simultaneously occurring inflammatory disease. Prealbumin, due to
      its short half-life, is a suitable indicator of changes in protein-energy
      balance, but its levels show, as with other serum proteins, a decrease in the
      case of inflammation too. The present study aimed to determine the prealbumin
      values of hospitalized geriatric patients and how they are affected by
      inflammatory disease. METHODS: In 101 patients aged over 80 years, the
      relationships were compared between prealbumin and C-reactive protein in the
      whole group and then in the subgroups with normal and increased C-reactive
      protein. RESULTS: In 67.33 % of hospitalized geriatric patients prealbumin was
      below the limit of the norm. A statistically highly significant dependence (p <
      0.001) was demonstrated between a decrease in prealbumin and an increase in C
      reactive protein in the whole group. In the subgroup with normal C-reactive
      protein, no statistically significant decrease in prealbumin was demonstrated,
      whereas in the subgroup with increased C-reactive protein a significant decrease
      in prealbumin (p < 0.001 for the whole group, p < 0.01 men, p < 0.05 women) was
      found. CONCLUSIONS: The study demonstrated subnormal mean initial values of
      prealbumin and a highly statistically significant negative correlation between a
      decrease in prealbumin and an increase in C-reactive protein in the whole group.
      We confirm that in inflammation there is a statistically significant decrease in
      serum concentration of prealbumin.

PMID- 18345264
TI  - What options does the supine-standing-supine test offer to patients with
      hypertension? Demonstrations of examples.
AB  - AIMS: The purpose of the study was to demonstrate autonomic nervous system (ANS)
      changes associated with treatment in hypertensive patients and utilization of
      these measurements in practice. METHODS: Hypertensive patients were examined
      before the start of treatment and after blood pressure compensation. The
      telemetric system VarCor PF 5 was used for non-invasive heart rate registration
      and automatic evaluation of heart rate variability (HRV) parameters. The supine
      standing-supine test with ortho-clinostatic loading in standard conditions was
      used for HRV evaluation. RESULTS: The influence of antihypertensive therapy on
      ANS was demonstrated in two cases. The first was a case of a responder to therapy
      and the second case was example of a non-responder to monotherapy regarding more
      therapeutic steps for blood pressure control. Different modes of results
      presentation are demonstrated: 3D graph, numeric form of standard parameters of
      HRV, computer interpretation of results by means of complex parameters and
      indices in numeric, graphic and verbal form with functional age calculation,
      cross graph of vagal activity index versus sympatho-vagal balance index was used
      for repeated measurements and follow-up. The increased spectral performance with
      augmented vagal activity and slope down of sympatho-vagal ratio are evident after
      blood pressure control achievement. Improvement of functional age parameter
      associated with blood pressure compensation is visible using a complex age
      dependent parameters interpretation. CONCLUSIONS: HRV evaluation in hypertensive
      patients provides new parameters for patient's examination. These parameters are
      influenced by both the illness itself and by pharmacotherapy. Such an approach
      offers more complex information about patient.

PMID- 18345265
TI  - Measurement of the blood flow velocity in the pericallosal artery of children
      with hydrocephalus by transcranial Doppler ultrasonography--preliminary results.
AB  - AIM: The goal of this study was to evaluate selected parameters of the Doppler
      curve of the pericallosal artery at children with hydrocephalus. METHODS: 12
      patients with hydrocephalus were divided into two groups. Group 1 comprised
      children needing cerebrospinal fluid drainage, and group 2 comprised children
      without any indication for drainage or with an already inserted well-functioning
      drainage system. Dilatation of the cerebral ventricles was determined by
      transcranial ultrasonography. Following parameters of a blood flow of the
      pericallosal branch of the anterior cerebral artery: peak systolic blood flow
      velocity (PSFV), end-diastolic blood flow velocity (EDFV) and resistive index
      (RI) were observed by transcranial Doppler ultrasonography. Parameters of The
      Doppler curve were measured without pressure (baseline parameters) and during
      compression of the anterior fontanelle (pressure provocation test). RESULTS:
      Group 1: baseline parameters: PSFV 68.9 +/- 13.52 cm/s, EDFV 18.26 +/- 10.39
      cm/s, RI 0.76 +/- 0.12; parameters during pressure provocation test: PSFV 66.92
      +/- 19.75 cm/s, EDFV 10.88 +/- 11.18 cm/s, RI 0.86 +/- 0.14. Group 2: baseline
      parameters: PSFV 59.95 +/- 19.38 cm/s, EDFV 20.65 +/- 8 cm/s, RI 0.65 +/- 0.04;
      parameters during the pressure provocation test: PSFV 57.14 +/- 18.91 cm/s, EDFV
      17.7 +/- 8.3 cm/s, RI 0.68 +/- 0.05. CONCLUSION: The results show increased
      baseline and postcompressive values of RI of pericallosal artery in infants with
      hydrocephalus before drainage procedure and normal values of RI at children
      without the need for cerebrospinal fluid drainage or with a well-functioning
      drainage system.

PMID- 18345266
TI  - Simultaneous endoscopic radial artery and great saphenous vein harvesting for
      redo coronary artery bypass grafting. A report of two cases.
AB  - AIM: An ageing population and increase in patient co-morbidities are forcing
      cardiac surgeons to meticulously consider the benefits and risks of respective
      conduits and their harvesting techniques. CASE REPORTS: Two cases of simultaneous
      endoscopic radial artery and great saphenous vein harvesting, for redo coronary
      artery bypass grafting, are presented. A shortage of venous conduits after
      previous bypass grafting, as well as the presentation of several risk factors of
      wound-healing complications, favoured simultaneous utilisation of both endoscopic
      techniques. CONCLUSION: Endoscopic vessel harvesting together with the pre
      harvesting duplex study is able to gain not only high-quality conduits but also
      minimize the risk of wound-healing and neurological disturbances associated the
      saphenous vein and radial artery harvesting.

PMID- 18345267
TI  - Vacuum-assisted closure in the treatment of sternal wound infection after cardiac
      surgery.
AB  - AIM: Vacuum-assisted closure (VAC) was primarily designed for the treatment of
      pressure ulcers or chronic, debilitating wounds. Recently, VAC has become an
      encouraging treatment modality for sternal wound infection after cardiac surgery,
      providing superior results to conventional treatment strategies. METHODS: From
      November 2004 to September 2006, 34 patients, undergoing VAC therapy for sternal
      wound infection following cardiac surgery, were prospectively evaluated. Ten
      patients (29 %) were treated for superficial sternal wound infection and 24 (71
      %) for deep sternal wound infection. The median age was 69.9 years (range 48 to
      82) and the median BMI was 33.4 kg/m(2) (range 28 to 41). Twenty patients (59 %)
      were women and 19 patients (59 %) were diabetics. Owing to sternal wound
      infection complications, 16 patients (47 %) were readmitted to the department.
      VAC was used following the previous failure of the conventional treatment
      strategy in 7 patients (21 %). RESULTS: Thirty-three patients (97 %) were treated
      successfully. One patient (3 %) died of multiple organ failure. The overall
      length of hospitalization was 34.6 days (range 9 to 62). The median number of
      dressing changes was 4.6 (range 3 to 10). The median VAC treatment time until
      surgical closure was 9.2 days (range 6 to 21 days). VAC therapy was solely used
      as a bridge to definite wound closure. Three patients (9 %) with chronic fistula
      were re-admitted 1 to 6 months after VAC therapy. CONCLUSIONS: VAC therapy is a
      safe and reliable option in the treatment of sternal wound infection in cardiac
      surgery. VAC therapy should be considered an effective adjunct to conventional
      treatment modalities for the treatment of extensive and life-threatening wound
      infections following cardiac surgery, particularly in the presence of risk
      factors.

PMID- 18345268
TI  - Influence of gender on the onset and duration of rocuronium-induced neuromuscular
      block.
AB  - AIMS: To assess the influence of gender on the course of rocuronium-induced
      neuromuscular block following a single bolus dose of 2 x ED(95) (0.6 mg kg(-1)).
      METHODS: Following the ethics committee approval and informed consent, 245
      patients (121 men, 124 women) scheduled for elective general surgery under TIVA
      with muscle relaxation were studied. After rocuronium 0.6 mg kg(-1), the onset
      time for maximal depression of T(1), clinical duration until 25 % recovery and
      recovery index (T(1) from 25 to 75 %) were determined with TOF-Watch SX
      accelerometric monitor. The data for male and female groups were compared with
      appropriate statistical tests (Student's unpaired t-test, Mann-Whitney Rank Sum
      Test and Fisher's exact test). RESULTS: Men were significantly larger (p < 0.001)
      and heavier (p < 0.05) than women, but the body mass index was comparable (ns).
      The onset time was shorter in females [92.5 (SD 14.2) vs. 104.7 (12.2) s, p <
      0.0001]. Clinical duration was increased in females [43.1 (7.9) vs. 31.3 (5.5)
      min; p < 0.0001], while the recovery index was identical in both groups [14.7
      (5.0) min in females and 14.8 (4.0) min in males; ns]. CONCLUSIONS: Women are
      more sensitive than men to the dose 0.6 mg kg(-1) of rocuronium. Under the study
      conditions described, the onset time was shortened and the clinical duration
      increased in female patients. This suggests that the routine dose of rocuronium
      should be reduced in women.

PMID- 18345269
TI  - Treatment with statins and involvement of the peripheral nervous system: results
      of a prospective clinical and neurophysiological follow-up.
AB  - AIMS: To study the pathological changes in neurophysiological examination of
      lower-limb peripheral nerves in patients with long-term statin treatment.
      METHODS: Forty-two patients (23 males, 19 females, mean age 51.9 and 52.3 years)
      with a definitive diagnosis of combined hyperlipidemia were studied. Other
      metabolic disorders or chronic ethanol abuse were excluded. Initial examinations
      included laboratory and neurophysiological measures (peroneal and tibial nerves:
      MNCV, CMAP, F-wave mean latency; superficial peroneal and sural nerve: SNCV,
      SNAP). Subsequently, treatment with simvastatin 20mg daily was initiated.
      Patients were followed for 24 months with examinations at 1, 6, 12 and 24 months
      after statin treatment initiation. RESULTS: None of the patients reported
      subjective symptoms typical for polyneuropathy. In laboratory findings, there was
      no elevation of muscle enzymes. Nevertheless, electrophysiological examination of
      lower-limb peripheral nerves demonstrated statistically significant prolongation
      of F-wave mean latency on peroneal and tibial nerves (p < 0.0001, paired t-test).
      A control group of 50 patients with combined hyperlipidemia but no statin
      treatment showed no changes over the same time interval. The study demonstrated
      that long-term CONCLUSIONS: The study demonstrated that long-term treatment with
      statins might cause a clinically silent but still electrophysiologically definite
      damage to peripheral nerves.

PMID- 18345270
TI  - AquaLase versus NeoSoniX--a comparison study.
AB  - AIMS: To compare the metrics and surgical outcome when using Infiniti AquaLase
      and NeoSoniX cataract removal modalities. METHODS: This prospective clinical
      study involved 50 patients with bilateral cataracts and lens removal using
      AquaLase in the right eye and NeoSoniX in the left eye. Best corrected visual
      acuity (BCVA), endothelial cell density and pachymetry were evaluted pre- and
      postoperatively. Statistical analysis was performed using the Wilcoxon Signed-
      Rank Test. RESULTS: Preoperative mean pachymetry was 569 +/- 31 mu in the right
      eye (RE) and 560 +/- 37 mu in the left eye (LE), mean endothelial cell density
      2744 +/- 418 cells/mm(2) (RE) and 2730 +/- 472 cells/mm(2) (LE). One week after
      operation pachymetry was 576 +/- 52 mu (RE) and 583 +/- 72 mu (LE) and
      endothelial cell density 2388 +/- 586 cells/mm(2) (RE) and 2463 +/- 615
      cells/mm(2) (LE). One month after surgery pachymetry was 556 +/- 43 mu (RE) and
      559 +/- 44 mu (LE) and endothelial cell density 2368 +/- 52 cells/mm(2) (RE) and
      2495 +/- 548 cells/mm(2) (LE). BCVA improved in all eyes and was 0.8 or better on
      the first postoperative day. CONCLUSIONS: Both the NeosoniX and AquaLase minimize
      intraoperative damage to ocular structures.

PMID- 18345271
TI  - A comparison of mammography and ultrasonography in the evaluation of breast
      masses.
AB  - AIM: Aim of the study is to evaluate breast masses using mammography (MG) and
      ultrasonography (USG) independently and in combination. MATERIALS AND METHODS:
      Our study group consisted of 62 female patients, with breast symptoms such as
      palpable lumps, pain in the breast and nipple discharge who were examined
      prospectively over a period of 6 months. All 62 patients were examined by both MG
      and USG independently. Fine needle aspiration cytology (FNAC) or core cut biopsy
      was done according to the findings of MG and USG and then the results were
      correlated with each modality finding. RESULTS: According to this study MG showed
      an efficiency of 81.8 % compared to 95.5 % for USG in detecting fibrocystic
      mastitis. However their combined approach resulted in 100 %. In the case of
      fibroadenomas, MG showed 75 % efficiency and USG only 35 % and the combination
      resulting in 93.7 %. For carcinomas, MG had an efficiency of 77.8 % and USG 55.6
      %, but the combination had an efficiency of 98.1 %. Overall, the
      histopathological results when correlated with each modality finding showed that
      MG had an efficiency of only 77.4 % and USG only 69.8 % when used alone in
      detecting these lesions of the breast compared to an efficiency of 98.1 %
      obtained by their combined approach. In our study, we showed that there was no
      significant difference in sensitivity between MG and USG (p = 0.3768) but there
      was significant difference in MG alone and MG-USG combination (p = 0.0015) and
      USG alone and USG-MG combination (p = 0.0001). CONCLUSION: Our study confirmed
      that combined MG and USG had higher sensitivity rate than the sensitivity rate
      observed for either single modality. The diagnostic accuracy for carcinomas of
      the breast appear to improve when MG was combined with USG, even in cases which
      showed no evidence of microcalcification or other signs of abnormalities. Our
      study implies that, USG may be the only viable modality in pregnant and lactating
      women as it does not involve ionizing radiation and also in dense breast tissue,
      as density is a limiting factor for MG.

PMID- 18345272
TI  - Discrepancy in ultrasound biometric parameters of the head (HC--head
      circumference, BPD--biparietal diameter) in breech presented fetuses.
AB  - BACKGROUND: A comparison of fetal ultrasonographic biometric parameters of the
      head (head circumference - HC, biparietal diameter - BPD) in breech presented
      fetuses. METHODS: Ultrasound biometry was performed in accordance with the method
      presented in the reference tables. In all breech presented fetuses, the HC, BPD
      and FL (femur length) were measured. High-risk and multiple pregnancies were
      excluded from the study. RESULTS: A total of 111 ultrasonographic biometries were
      performed between the 31(st) - 38(th) week of gestation. Fetuses in the breech
      position had a significantly lower BPD compared to HC and FL. The difference
      between BPD and HC was 16.2 days (95%Cl 14.3-18.1; p = 0.001). Maternal age at
      delivery was 20 - 36 years (average 28.1; median 28.0). CONCLUSIONS: According to
      our results, fetuses in the breech position have a significantly lower BPD
      compared to HC or FL. HC and FL parameters correlate with gestational age. In
      cases of ultrasonographic biometric discrepancy between BPD and FL, the fetal
      position should be taken into account. Breech-presented fetuses have an elongated
      head shape and ultrasound biometrics should evaluate its circumference (HC). It
      is important to responsibly interpret the results so as not to stress the
      expecting mother with suspicions of fetal pathology.

PMID- 18345273
TI  - Time analysis of hard and soft bolus processing.
AB  - OBJECTIVE: Clinical observations and mathematical models show that dental
      implants are influenced by the magnitude of loading. Therefore, the knowledge of
      mandible movement during mastication is important to assess occlusal and
      masticatory force vectors. The purpose of this study was to detect the path of
      movement of the lower jaw and to distinguish stages of mastication, duration of
      bolus processing and peak amplitude of mastication. METHOD: Motion analysis was
      used to record three-dimensional mandible movements. Individualized sensors were
      rigidly attached to the mandible of 51 study participants. At the beginning of
      the measurement, all subjects were asked to move the mandible in extreme
      positions (maximal opening and maximal lateral movements). Then, each subject
      masticated a bite of hard and soft food. Duration of bolus mastication and peak
      amplitude of mastication movement in mesio-distal, cranio-caudal and vestibulo
      oral axes related to peak amplitude of marginal movements were evaluated for each
      subject. The chewing record of each subject was divided into three phases
      (chopping, grinding and swallowing), and the duration of mastication and number
      of closing movements were evaluated. RESULTS: The findings of this pilot study
      suggest that masticatory movements vary in individuals. Bolus character
      influences the process duration, but not the frequency of closing movements.
      Neither gender nor age had any influence on either the time or frequency of bolus
      processing. CONCLUSION: Relationships to directions and magnitudes of acting
      chewing force should be more precisely examined since transversally acted forces
      during grinding are important factors in tooth/implant overloading.

PMID- 18345274
TI  - Oral lichenoid lesions and allergy to dental materials.
AB  - BACKGROUND: Dental materials, oral hygiene products and food additives may cause
      contact allergic reactions in the mouth with varied clinical presentation. Oral
      lichenoid lesions (lichen planus-like lesions) can be induced by hypersensitivity
      to dental restorative metals, acrylates, flavorings and other substances. AIM:
      The aim of this study was to demonstrate contact allergy to dental materials in
      patients with oral lichenoid lesions using patch tests. PATIENTS AND METHODS:
      Routine patch tests with two sets of allergens - "European Standard" and "Dental
      Screening" (Chemotechnique Diagnostics, Sweden) supplemented with pulverized
      amalgam, iridium, indium, menthol, sorbic acid and platinum were done on a set of
      25 patients with lichenoid lesions located on the buccal mucosa, tongue and lips.
      Application and interpretation of the tests were conducted according to ICDRG
      (International Contact Dermatitis Research Group). RESULTS: 15 (60 %) patients
      showed sensitization to 1 or more allergens, with a total of 31 positive
      reactions. The greatest frequency of positive reactions was to dental metals,
      with a total of 27 positive reactions. The order of tested metals according to
      frequency of positive reactions was mercury (6/25/24 %), amalgam (6/25/24 %),
      nickel (4/25/16 %), palladium (4/25/16 %), cobalt (3/25/12 %), gold (2/25/8 %),
      chrome (1/25/4 %), indium (1/25/4 %). The clinical relevance of the results with
      regard to the material's presence in the mouth was demonstrated in 11 (44 %)
      patients. In 9 patients, replacement of the positively tested materials led to
      healing or to significant regression of mucosal changes. CONCLUSIONS: The results
      of the patch tests showed the possible contribution of contact sensitization in
      the pathogenesis of lichenoid manifestations in the oral cavity. Due to the
      premalignant character of these lesions, replacement of positively tested
      materials and follow up of these patients is advised.

PMID- 18345275
TI  - Early fracture of a plasma cup ceramic liner: a case report and surface analysis.
AB  - BACKGROUND: Ceramic surfaces offer excellent tribological properties and for this
      reason are frequently used in younger patients with osteoarthritis of the hip.
      However, they may fracture easily owing to low tolerance to tensile and impact
      stresses in particular. We report a case of early fracture of a currently
      available ceramic liner in a 44-year-old woman with revision total hip
      arthroplasty. METHODS AND RESULTS: Scanning electron microscopy and macroscopic
      fractographic examination were done to elucidate the cause of failure. These
      showed the fracture started most probably at the inner surface of the cup.
      Several mechanisms of fracture initiation are discussed in the paper. CONCLUSION:
      This is the first report on early fracture of the Plasma cup ceramic liner in
      white man. The fracture occurred intraoperatively or early postoperatively while
      the diagnosis was determined much later despite the patient had experienced
      sensations of subluxations long time before.

PMID- 18345276
TI  - Azygos vein injury in blunt chest trauma.
AB  - Injuries to the azygos vein in a blunt chest trauma are uncommon and have
      previously been described in only 21 cases. The diagnosis is crucially based on
      massive right haemothorax with signs of shock, hypotension and altered mental
      status. The severity of the trauma, speed of transport and surgical intervention
      are often decisive for the survival of the patient. This is confirmed by the
      three cases we report below.

PMID- 18345277
TI  - Haemotherapy analysis: the Teaching Hospital Olomouc in 2006.
AB  - AIMS: Annual evaluation of blood transfusion preparation administration at the
      University Hospital Olomouc, Czech Republic as a contribution to the European
      Union haemovigilance system. METHODS: Analysis of blood transfusion preparations
      released from the Department of Blood Transfusion of the above university
      hospital and laboratory examination results in receivers of these products for
      the year 2006. Total hospital consumption and usage in particular medical
      disciplines in the hospital were assessed. RESULTS: Red cell concentrates: in
      total 14 347 TU (deleucotised in 20.4 %). Departments according to usage:
      surgery, haematooncology, anaesthesiology and surgery intensive care department,
      and internal medicine department. Haemoglobin levels were above 100 g/L before
      blood transfusion administration in 24 % of cases. Platelets: in total 1 712 TU
      (100 % manufactured by apheresis, 56 % deleucotised). Platelet counts below 20 x
      10(9)/L were found in all cases before platelet concentrate administration.
      Plasma: in total 5 959 TU to 1 297 of patients. Departments according to usage:
      surgery, anaesthesiology and surgery intensive care department, internal medicine
      and haematooncology. Two hundred and forty nine cases without coagulation
      parameter monitoring and 333 (25.67 %) patients with only 1 TU of administered
      plasma were found. CONCLUSIONS: The incorrect indications for red cell
      transfusion preparations were found in eleven patients with haemoglobin levels
      above 130 g/L. Underdosing in 25.67 % of plasma administrations signifies dubious
      indications in these cases. Implementation of the haemovigilance system in
      practice is now mandatory for the Czech Republic after joining the European
      Union. Therefore more precise data and analysis of questionable cases with
      further education of staff in clinical departments are essential for the
      haemovigilance principle to be applied on a hospital basis in the Czech Republic.

PMID- 18345278
TI  - The F1-F2 vowel chart for Czech whispered vowels a, e, i, o, u.
AB  - AIM: The aim of this contribution is to present the formant chart of the Czech
      vowels a, e, i, o, u and show that this can be achieved by means of digital
      methods of sound processing. METHOD: A group of 35 Czech students of the
      Pedagogical Faculty of Palacky University was tested and a record of whispered
      vowels was taken from each of them. The record was digitalized and processed by
      the Discrete Fourier Trasform. The result is the power spectrum of the individual
      vocals - the graphic output consists of a plot of the relative power of
      individual frequencies in the original sound. The values of the first two maxima
      which represent the first and the second formants were determined from the graph.
      The values were plotted on a formant chart. RESULTS: Altogether, 175 spectral
      analyses of individual vowels were performed. In the resulting power spectrum,
      the first and the second formant frequencies were identified. The first formant
      was plotted against the second one and pure vocal formant regions were
      identified. CONCLUSION: Frequency bands for the Czech vowel "a" were
      circumscribed between 850 and 1150 Hz for first formant (F1) and between 1200 and
      2000 Hz for second formant (F2). Similarly, borders of frequency band for vowel
      "e" they were 700 and 950 Hz for F1 and 1700 and 3000 Hz for F2. For vowel "i"
      300 and 450 Hz for F1 and 2000 and 3600 Hz for F2, for vowel "o" 600 and 800 Hz
      for F1 and 600 and 1400 Hz for F2, for vowel "u" 100 and 400 Hz for F1 and 400
      and 1200 Hz for F2. DISCUSSION: At low frequencies it is feasible to invoke the
      source-filter model of voice production and associate vowel identity with
      frequencies of the first two formants in the voice spectrum. On the other hand,
      subject to intonation, singing or other forms of exposed voice (such as emotional
      speech, focused speech), the formant regions tend to spread. In spectral analysis
      other frequencies dominate, so specific formant frequency bands are not easily
      recognizable. Although the resulting formant map is not much different from the
      formant map of Peterson, it carries basic information about specific Czech
      vowels. The results may be used in further research and in education.

PMID- 18345280
TI  - Characteristics of lethal electrical injuries in central and northeastern
      Bulgaria for a 27-year period (1980-2006).
AB  - OBJECTIVE: Despite the advancement of forensic science, electro-traumas still
      pose serious challenges. METHODS: We have studied the forensic medical
      documentation from 485 autopsies following electro-trauma over the period 1980
      2006, performed at the forensic wards in 6 districts of the country The
      statistical analysis includes comparison of means and percentages. They are
      carried out using SPSS Version 11. We accepted statistical significant values of
      P equals; .05. RESULTS: The incidence of lethal injuries caused by electricity is
      1.29 cases per 100000 people per year. The average age of the deceased from
      electro-trauma is 37.3 years. Men (85%) prevails over women (14.84%). There are
      24.32% of the cases that are work-related accidents, and 60.61% of them are
      domestic. Suicide through electrocution is relatively rare: 7.21%. Homicide has
      not been registered in our study. Low-voltage injuries (42.06%) are more common
      than high-voltage ones (30.72%). 62.68% of the lethal cases occur in summer,
      between June and September. CONCLUSIONS: Among the studied cases, electro-trauma
      occurs at a young age. The victims are typically men. Work-related accidents are
      more common than domestic ones; injuries by low voltage are observed more
      frequently than those by high voltage. Suicides are very rare, and not a single
      case of homicide has been observed in the study. There exists a seasonal
      variation in incidence of lethal accidents caused by electric current, its peak
      being during the summer months.

PMID- 18345281
TI  - Traction, contraction ... attraction.

PMID- 18345282
TI  - Mentosternal contracture treated with an occipito-scapular flap in a 5-year-old
      boy: a case report.
AB  - OBJECTIVE: Mentosternal contracture, a complication of deep thermal injury to the
      neck, results in significant functional and esthetic problems. A new method of
      reconstructing this deformity is described. METHODS: We present a case of a 5
      year-old patient with severe mentosternal contracture, treated with a large
      occipito-scapular island flap (24 cm x 10 cm) augmented by anastomosing the
      circumflex scapular artery to the facial artery. RESULTS: A 46% functional
      improvement in the range of motion was achieved, and an esthetically pleasing
      appearance was obtained. CONCLUSIONS: This case report demonstrates the
      occipitocervical dorsal flap to be an excellent option for mentosternal
      contracture release. Microvascular flap perfusion augmentation should be
      considered even in cases of limited vascular dimensions as is often seen in the
      pediatric patient population.

PMID- 18345283
TI  - Computerized two-lead resting ECG analysis for the detection of coronary artery
      stenosis after coronary revascularization.
AB  - BACKGROUND: Resting electrocardiogram (ECG) shows limited sensitivity and
      specificity for the detection of coronary artery disease (CAD), where patients
      with a history of coronary revascularization may pose special challenges. Several
      methods exist to enhance sensitivity and specificity of resting ECG for diagnosis
      of CAD, but such methods are not better than a specialist's judgement. We
      compared a new computer-enhanced, resting ECG analysis device, 3DMP, to coronary
      angiography to evaluate the device's accuracy in detecting hemodynamically
      relevant CAD. METHODS: A convenience sample of 172 patients with a history of
      coronary revascularization scheduled for coronary angiography was evaluated with
      3DMP before coronary angiography. 3DMP's sensitivity and specificity in detecting
      hemodynamically relevant coronary stenosis as diagnosed with coronary angiography
      were calculated as well as odds ratios for the 3DMP severity score and coronary
      artery disease risk factors. RESULTS: The 3DMP system accurately identified 50 of
      55 patients as having hemodynamically relevant stenosis (sensitivity 90.9%,
      specificity 88.0%). Positive and negative predictive values for the
      identification of coronary stenosis as diagnosed in coronary angiograms were
      62.7% and 97.8% respectively. Risk and demographic factors in a logistic
      regression model had a markedly lower predictive power for the presence of
      coronary stenosis in these patients than did 3DMP severity score (odds ratio 2.04
      [0.74-5.62] vs. 73.57 [25.10-215.68]). A logistic regression combining severity
      score with risk and demographic factors did not add significantly to the
      prediction quality (odds ratio 80.00 [27.03-236.79]). CONCLUSIONS: 3DMP's
      computer-based, mathematically derived analysis of resting two-lead ECG data
      provides detection of hemodynamically relevant CAD in patients with a history of
      coronary revascularization with high sensitivity and specificity that appears to
      be at least as good as those reported for other resting and/or stress ECG methods
      currently used in clinical practice.

PMID- 18345284
TI  - Shedding light on the role of Vitreoscilla hemoglobin on cellular catabolic
      regulation by proteomic analysis.
AB  - Heterologous expression of Vitreoscilla hemoglobin (VHb) has been reported to
      improve cell growth, protein synthesis, metabolite productivity and nitric oxide
      detoxification. Although it has been proposed that such phenomenon is attributed
      to the enhancement of respiration and energy metabolism by facilitating oxygen
      delivery, the mechanism of VHb action remains to be elucidated. In the present
      study, changes of protein expression profile in Escherichia coli as a consequence
      of VHb production was investigated by two-dimensional gel electrophoresis (2-DE)
      in conjunction with peptide mass fingerprinting. Total protein extracts derived
      from cells expressing native green fluorescent protein (GFPuv) and chimeric
      VHbGFPuv grown in Luria-Bertani broth were prepared by sonic disintegration. One
      hundred microgram of proteins was individually electrophoresed in IEF-agarose rod
      gels followed by gradient SDS-PAGE gels. Protein spots were excised from the
      gels, digested to peptide fragments by trypsin, and analyzed using matrix
      assisted laser desorption ionization-time of flight (MALDI-TOF) mass
      spectrometry. Results revealed that expression of VHbGFPuv caused an entire
      disappearance of tryptophanase as well as down-regulated proteins involved in
      various metabolic pathways, e.g. glycerol kinase, isocitrate dehydrogenase,
      aldehyde dehydrogenase, and D-glucose-D-galactose binding protein. Phenotypic
      assay of cellular indole production confirmed the differentially expressed
      tryptophanase enzymes in which cells expressing chimeric VHbGFP demonstrated a
      complete indole-negative reaction. Supplementation of delta-aminolevulinic acid
      (ALA) to the culture medium enhanced expression of glyceraldehyde-3-phosphate
      dehydrogenase and glycerol kinase. Our findings herein shed light on the
      functional roles of VHb on cellular carbon and nitrogen consumptions as well as
      regulation of other metabolic pathway intermediates, possibly by autoregulation
      of the catabolite repressor regulons.

PMID- 18345286
TI  - Stent versus surgery.
AB  - Following the introduction of percutaneous and endoscopic biliary drainage there
      has been an ongoing debate about the indications and outcomes of endoscopic
      versus surgical drainage in a variety of bilio-pancreatic disorders. The evidence
      based literature concerning four different areas of pancreatobiliary diseases
      have been reviewed. Preoperative endoscopic biliary drainage in patients with
      obstructive jaundice should not be used routinely but only in selected patients.
      For patients with biliary leakage and bile duct strictures after a laparoscopic
      cholecystectomy, endoscopic stent therapy might be first choice and surgery
      should be used for failures of endoscopic treatment. Surgery is the treatment of
      choice after transection of the bile duct (the major bile duct injuries). The
      majority of patients with obstructive jaundice due to advanced pancreatic cancer
      will undergo endoscopic drainage but for relatively fit patients with a prognosis
      of more than 6 months, surgical drainage or even palliative resection might be
      considered. For patients with persistent pain due to chronic pancreatitis
      surgical drainage combined with limited pancreatic head resection might be first
      choice for pain relief. Most importantly, the management of patients with these
      pancreatobiliary diseases should be performed by a multidisciplinary HPB approach
      and teamwork consisting of gastroenterologists, radiologists and surgeons.

PMID- 18345287
TI  - Acute pancreatitis--from cellular signalling to complicated clinical course.
AB  - Acute pancreatitis (AP) is a common disease that has a mild to moderate course in
      most cases. During the last decade, a change in diagnostic facilities as well as
      improved intensive care have influenced both morbidity and mortality in AP.
      Still, however, a number of controversies and unresolved questions remain
      regarding AP. These include prognostic factors and how these may be used to
      improve outcome, diagnostic possibilities, their indications and optimal timing,
      and the systemic inflammatory reaction (systemic inflammatory response syndrome-
      SIRS) and its effect on the concomitant course of the disease and potential
      development of organ failure. The role of the gut has been suggested to be
      important in severe AP, but has recently been somewhat questioned. Despite
      extensive research, pharmacological and medical intervention of proven clinical
      value is scarce. Various aspects on surgical interventions, including endoscopic
      sphincterotomy, cholecystectomy and necrosectomy, as regards indications and
      timing, will be reviewed. Last, but not least, are the management of late
      complications and long-term outcome for patients with especially severe AP.

PMID- 18345288
TI  - Biliary tract obstruction in chronic pancreatitis.
AB  - Bile duct strictures are a common complication in patients with advanced chronic
      pancreatitis and have a variable clinical presentation ranging from an incidental
      finding to overt jaundice and cholangitis. The diagnosis is mostly made during
      investigations for abdominal pain but jaundice may be the initial clinical
      presentation. The jaundice is typically transient but may be recurrent with a
      small risk of secondary biliary cirrhosis in longstanding cases. The management
      of a bile duct stricture is conservative in patients in whom it is an incidental
      finding as the risk of secondary biliary cirrhosis is negligible. Initial
      conservative treatment is advised in patients who present with jaundice as most
      will resolve once the acute on chronic attack has subsided. A surgical biliary
      drainage is indicated when there is persistent jaundice for more than one month
      or if complicated by secondary gallstones or cholangitis. The biliary drainage
      procedure of choice is a choledocho-jejunostomy which may be combined with a
      pancreaticojejunostomy in patients who have associated pain. Since many patients
      with chronic pancreatitis have an inflammatory mass in the head of the pancreas,
      a Frey procedure is indicated but a resection should be performed when there is
      concern about a malignancy. Temporary endoscopic stenting is reserved for
      cholangitis while an expandable metal stent may be indicated in patients with
      severe co-morbid disease.

PMID- 18345289
TI  - Single hepatocellular carcinoma ranging from 3 to 5 cm: radiofrequency ablation
      or resection?
AB  - BACKGROUND: The optimal therapy for hepatocellular carcinoma (HCC) is
      transplantation. For all those patients not eligible for transplantation (or on
      the waiting list) among the treatments of choice used more frequently in recent
      years are resection (RES) and radiofrequency ablation (RFA). RFA is less
      efficacious for HCC ranging over 3 cm. The aim of this study was to compare RFA
      to RES in a restricted cohort of patients with a single naive HCC ranging from 3
      to 5 cm in size and without end-stage liver disease. PATIENTS AND METHODS. A
      total of 102 patients who had never been treated before were enrolled. Those
      patients whose HCC position would have required too much parenchymal loss at RES
      (central or close to main vascular structures) were treated with RFA (n=60), and
      the others underwent RES (n=42). The two groups were similar for HCC size and
      liver disease status. The outcome was considered in terms of overall survival
      (OS) and disease-free survival (DFS) calculated by the Kaplan-Meier method.
      Differences among groups were validated by log-rank test. RESULTS: The RES group
      seemed to present a better long-term OS (91%, 57%, and 43% vs 96%, 53%, and 32%
      at 1, 3, and 5 years, respectively) and DFS (74%, 35%, and 14% vs 68%, 18%, and
      0%, respectively) but there was no statistical significance. Age, gender, virus
      etiology, HCC size and alpha-fetoprotein levels did not correlate with survival.
      Patients with recurrence within the first 12 months after treatment showed a
      worse long-term survival (p=0.011). Patients in Child-Pugh class B had poor
      prognoses compared with those in class A (p=0.047). CONCLUSION: Even if RES
      seemed to promise better long-term results, in the medium term this difference
      had no statistical significance. Survival in this series was more closely related
      to the stage of the underlying liver disease than to treatment (RES/RFA).

PMID- 18345290
TI  - Liver resection for non-colorectal, non-neuroendocrine metastases: analysis of a
      multicenter study from Argentina.
AB  - BACKGROUND AND AIM: Resection of colorectal liver metastases has become a
      standard of care, although the value of this procedure in non-colorectal non
      neuroendocrine (NCRNNE) metastases remains controversial and is still a matter of
      debate. The aim of the study was to determine the utility of liver resection in
      the long-term outcome of patients with NCRNNE metastases. MATERIAL AND METHODS:
      The records of 106 patients who underwent liver resection for NCRNNE metastases
      in the period 1989 to 2006 at 5 HPB Centers in Argentina were analyzed. Patient
      demographics, tumor characteristics, type of resection, long-term outcome and
      prognostic factors were analyzed. Depending on primary tumor sites, a comparative
      analysis of survival was performed. RESULTS: Mean age was 54 (17-76). Hepatic
      metastases were solitary in 62.3% and unilateral in 85.6%. Primary tumor sites:
      Urogenital (37.7%), sarcomas (21.7%), breast (17.9%), gastrointestinal (6.6%),
      melanoma (5.7%), and others (10.4%). Fifty-one major hepatectomies and 55 minor
      resections were performed. Twenty patients underwent synchronous resections. An
      R0 resection could be achieved in 89.6%. Perioperative mortality was 1.8%.
      Overall, 1-year, 3-year, and 5-year survival rates were 67%, 34%, and 19%,
      respectively. Survival was significantly longer for metastases of urogenital
      (p=0.0001) and breast (p=0.003) origin. Curative resections (p=0.04) and
      metachronous disease (p=0.0001) were predictors of better survival. CONCLUSIONS:
      Liver resection is an effective treatment for NCRNNE liver metastases; it gives
      satisfactory long-term survival especially in metachronous disease, in patients
      with metastases from urogenital and breast tumors and when R0 procedures can be
      performed.

PMID- 18345291
TI  - Comparison between staple and vessel sealing device for parynchemal transection
      in laparoscopic liver surgery in a swine model.
AB  - BACKGROUND: Advancements in technology have allowed laparoscopic surgery to
      expand into advanced procedures such as liver resection; however, the transection
      method is debatable. This study was designed to evaluate the feasibility and
      outcome of laparoscopic liver resection comparing the vessel sealing device (VSD)
      versus endomechanical stapling devices for parenchymal transection in a swine
      model. MATERIALS AND METHODS: Laparoscopic left hepatectomy was performed in two
      groups (n=7 in each group) comparing the stapler device with the VSD. The cut
      surfaces of the liver were evaluated for bleeding and biliary leakage at the time
      of the operation and 1 week later. The animals were sacrificed 1 week after the
      operation to determine hemorrhage and bile leakage, and to allow histological
      evaluation of the liver. Serum liver enzymes were checked before, after, and 1
      week postoperatively. RESULTS: No evidence of biliary leakage or hemorrhage was
      noted at the time of the operation and 1 week later for both groups. There was a
      trend toward an increase in blood loss in the stapled group compared with
      LigaSure (40+/-16.4 cc vs 17+/-3.7 cc, p>0.05). There was also a trend toward
      shorter transection time in the stapled group compared with the LigaSure group
      (15+/-4.1 min vs 21.8+/-5.3, p>0.05). The instrument cost was significantly
      higher in the stapled group (720+/-110 vs 400+/-50; p<0.05). There was no
      difference in serial liver enzymes and liver histopathology in the two groups.
      CONCLUSIONS: The VSD and endomechanical stapler can be safely and effectively
      used for parenchymal transection during laparoscopic liver resection. However,
      using endomechanical staplers is associated with an increase in cost.

PMID- 18345292
TI  - Identification of mutation-prone points in bile salt export pump.
AB  - BACKGROUND: The bile salt export pump mediates uphill canalicular bile acid
      secretion. Inherited dysfunction of the bile salt export pump causes a
      progressive and a benign form of familial intrahepatic cholestasis. Mutations
      within the bile salt export pump gene are reported. Presently, prediction of
      protein nanostructure and function is a great challenge in the proteomics and
      structural genomics era. Identification of the point vulnerable to mutation is a
      new trend to expand knowledge on disorders at the genomic and proteomic level of
      diseases. MATERIALS AND METHODS: A bioinformatic analysis was performed to study
      the positions that determine peptide motifs in the amino acid sequence of the
      bile salt export pump. To identify the weak linkage in bile salt export pump, a
      new bioinformatic tool named GlobPlot was used. RESULTS: The positions 16-34, 119
      127, 451-459, 550-561, 1084-1099, 1108-1118, 1135-1140, 1211-1217, and 1314-1321
      were identified as the positions prone to mutation. CONCLUSION: Based on this
      study, the weak linkages in the bile salt export pump can be identified and can
      provide good information for expectation of possible new mutations that can lead
      to cross species jumping. In addition, the results from this study provide useful
      information for further research on the bile salt export pump.

PMID- 18345293
TI  - Probing the urinary proteome of severe acute pancreatitis.
AB  - BACKGROUND: Proteinuria is a characteristic feature of severe acute pancreatitis
      (SAP) that may allow unique insights into AP pathophysiology. This study used a
      proteomic approach to differentiate the abundant urinary proteins in AP patients.
      MATERIALS AND METHODS: Urine samples were prospectively collected from 4 groups
      (5 SAP, 10 mild gallstone AP, 7 mild alcohol AP, 7 controls). Reverse-phase high
      performance liquid chromatography (RP-HPLC) and matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (LC MALDI) were used to
      identify urinary proteins and determine any differences between the groups.
      RESULTS: There were 17 RP-HPLC major peaks in SAP groups of significantly greater
      absorbance magnitude than the corresponding ones in mild and control groups.
      Various mass spectrometry methods were used to identify 21 different parent
      proteins from these SAP peaks. They included fibrinogen, serum amyloid A, insulin
      and calcitonin gene-related peptides. There were no identifiable protein peaks at
      the corresponding elution times in the mild pancreatitis and controls samples.
      DISCUSSION: Proteomic techniques offer a unique unexplored window into AP
      pathophysiology. The utility of these proteins as markers of pancreatitis
      severity now need to be further investigated and the identification extended to
      the full urinary proteome as technology permits.

PMID- 18345294
TI  - Preoperative lymphocyte count as a prognostic factor in resected pancreatic
      ductal adenocarcinoma.
AB  - BACKGROUND AND AIMS: Recognized prognostic factors for resected pancreatic ductal
      adenocarcinoma (PDAC) include tumour size, differentiation, resection margin
      involvement and lymph node metastases. A further prognostic factor of less
      certain significance is lymphocyte count. The aim of this study was to
      investigate whether preoperative lymphocyte count is a prognostic indicator in
      patients with PDAC. MATERIAL AND METHODS: Patients who had undergone a
      potentially curative pancreaticoduodenectomy (PD) for PDAC between 1998 and 2005
      were analysed. Standard prognostic factors, preoperative lymphocyte count,
      preoperative neutrophil count and survival data were collected. RESULTS: Of the
      44 patients studied, univariate analysis identified predictors of a poor survival
      as lymph node status (node positive (+ve) 10.3 [5.4-20.9] months versus node
      negative (-ve) 14.2 [10.9-31.4] months; p=0.038), posterior resection margin
      invasion (margin +ve 7.0 [5.1-15.0] months versus margin -ve 13.1 [10.0-28.3]
      months; p=0.025) and lymphocyte count below the reference range (<1.5 x
      10(9)/litre 8.8 [7.0-13.1] months versus > or = 1.5 x 10(9)/litre 14.3 [7.0-28.3]
      months; p=0.029). Low preoperative lymphocyte count (p=0.027) and posterior
      margin invasion (p=0.023) retained significance on multivariate analysis.
      Preoperative neutrophil to lymphocyte ratio was not a significant prognostic
      factor. CONCLUSION: Preoperative lymphocyte count is a significant prognostic
      factor in patients with PDAC.

PMID- 18345295
TI  - Nodal sampling in pancreaticoduodenectomy: does it change our management?
AB  - BACKGROUND: Lymph node involvement in periampullary malignancy is the single most
      important factor in predicting survival in pancreaticoduodenectomy (PD). The role
      of nodal sampling in PD has not been well evaluated. This study evaluates the
      utility of nodal sampling of nodal stations 8 and 12, which are easily dissected
      early in PD, in overall final nodal status. PATIENTS AND METHODS: Fifty patients
      underwent PD at a single institution by a one surgeon over a 15 month period.
      Nodal stations 8 and 12 were sent separately for pathologic evaluation. Twenty
      eight patients had a final diagnosis of periampullary malignancy. Demographic and
      pathologic data were collected retrospectively from patient charts. Positive and
      negative predictive values of nodes 8 and 12 were evaluated. RESULTS: Eighteen of
      28 patients with a diagnosis of periampullary malignancy had pathologically
      negative nodes 8 and 12, and a final nodal status (all peripancreatic lymph
      nodes) negative for nodal involvement. Nine of 28 patients had a negative nodal
      sampling result, but a positive final nodal status for metastatic tumor. The
      remaining four patients had both positive nodal sampling and final nodal status
      for metastatic tumor. The negative predictive value of negative nodes 8 and 12
      was 0.625. CONCLUSION: The negative predictive of a negative node 8 and 12 of
      0.625 suggests that the decision to proceed with or abort PD should not be based
      on intraoperative evaluation of these nodes. Performance of PD should be
      undertaken if technically feasible, and not based on intraoperative nodal
      assessment.

PMID- 18345296
TI  - Total gastric necrosis due to aberrant arterial anatomy and retrograde blood flow
      in the gastroduodenal artery: a complication following pancreaticoduodenectomy.
AB  - Patients with coeliac artery occlusion often remain asymptomatic due to the rich
      collateral blood supply (pancreaticoduodenal arcades) from the superior
      mesenteric artery. However, division of the gastroduodenal artery (GDA) during
      pancreaticoduodenectomy may result in compromised blood supply to the liver,
      stomach and spleen. Postoperative complications associated with this condition
      are rarely reported in the literature. We report two cases of coeliac artery
      occlusion encountered during pancreaticoduodenectomy, one of which was
      complicated by hepatic ischaemia and total gastric infarction postoperatively.
      Based on our experience and review of the literature, a management algorithm for
      coeliac artery stenosis encountered during pancreaticoduodenectomy is proposed.

PMID- 18345297
TI  - The Medical and Surgical Department of Digestive Diseases and Minimally Invasive
      HPB Fellowship at IMM.
AB  - The Medical and Surgical Department at the Institut Mutualiste Montsouris
      combines all the medical and surgical specialists in digestive diseases to work
      together on the same team and in the same unit. It represents a novel approach to
      the care of the patient with pathology of the digestive system. A Minimally
      Invasive HPB Fellowship was created in 2006 because of the vast laparoscopic
      experience at this institution. It is the first such fellowship listed on the
      IHPBA website and appears to be the first of its kind. For surgeons interested in
      pursuing a career in minimally invasive HPB surgery, it is currently accepted
      that expertise in both laparoscopy and HPB surgery have been the only means to
      gain the ability to tackle advanced procedures in this complex field. However, as
      young surgeons continue to get an earlier exposure to more and more complex
      minimally invasive procedures during residency, the need to perform two
      fellowships may be eliminated and more centers like IMM may permit graduating
      residents to become experts in this field in 1 year.

PMID- 18345298
TI  - Perioperative transfusion for pancreaticoduodenectomy and its impact on prognosis
      in resected pancreatic ductal adenocarcinoma.
AB  - BACKGROUND AND AIMS: Pancreaticoduodenectomy (PD) is a major operative
      intervention performed most commonly for malignancy in the head of pancreas. The
      aim of this study was to evaluate the utilization of blood transfusion for PD and
      to determine whether this had prognostic significance in a subset of patients
      with pancreatic ductal adenocarcinoma (PDAC). MATERIAL AND METHODS: Data on blood
      transfusion requirement were retrospectively collected for patients undergoing PD
      from 1998 to 2005. Standard prognostic factors and survival data were also
      collected in patients with PDAC. RESULTS: One-hundred-and-seventy patients
      underwent PD. Seventy-six patients (45%) received transfusion. The median
      (interquartile range) number of units of red cell concentrate (RCC) transfused
      perioperatively (intraoperatively and within 24 h of surgery) was 1.5 (0.5-2.5).
      The median preoperative haemoglobin (Hb) was 126 g/dl. The median number of units
      of RCC transfused perioperatively in patients with Hb <126 g/dl was 2 (1-3); for
      those with Hb > or = 126 g/dl the median was 0 (0-1); p=0.003. Forty-nine
      patients who were resected for PDAC were subjected to survival analysis.
      Univariate and multivariate analyses showed that only posterior resection margin
      invasion was associated with an adverse outcome (margin positive 198 [143-470]
      days vs margin negative 398 [303-859] days; p=0.02). Perioperative RCC
      transfusion requirement was not a significant predictor of survival (transfusion
      408 [214-769] days vs no transfusion 331 [217-391] days; p=0.18). Furthermore,
      RCC transfusion within 30 days of operation was not a significant predictor of
      poor survival (transfusion 331 [201-459] days vs no transfusion 317 [196-769]
      days; p=0.43). CONCLUSIONS: PD can be performed with a moderately low requirement
      for RCC transfusion; however, low preoperative haemoglobin is a predictor for the
      requirement of RCC transfusion. Administration of RCC transfusion does not appear
      to be a significant adverse prognostic factor in patients with resected PDAC.

PMID- 18345299
TI  - Critical appraisal of a manuscript.

PMID- 18345300
TI  - Practical questions in liver metastases of colorectal cancer: general principles
      of treatment.
AB  - Liver metastases of colorectal cancer are currently treated by multidisciplinary
      teams using strategies that combine chemotherapy, surgery and ablative
      techniques. Many patients classically considered non-resectable can now be
      rescued by neoadjuvant chemotherapy followed by liver resection, with similar
      results to those obtained in initial resections. While many of those patients
      will recur, repeat resection is a feasible and safe approach if the recurrence is
      confined to the liver. Several factors that until recently were considered
      contraindications are now recognized only as adverse prognostic factors and no
      longer as contraindications for surgery. The current evaluation process to select
      patients for surgery is no longer focused on what is to be removed but rather on
      what will remain. The single most important objective is to achieve a complete
      (R0) resection within the limits of safety in terms of quantity and quality of
      the remaining liver. An increasing number of patients with synchronous liver
      metastases are treated by simultaneous resection of the primary and the liver
      metastatic tumours. Multilobar disease can also be approached by staged
      procedures that combine neoadjuvant chemotherapy, limited resections in one lobe,
      embolization or ligation of the contralateral portal vein and a major resection
      in a second procedure. Extrahepatic disease is no longer a contraindication for
      surgery provided that an R0 resection can be achieved. A reverse surgical staged
      approach (liver metastases first, primary second) is another strategy that has
      appeared recently. Provided that a careful selection is made, elderly patients
      can also benefit from surgical treatment of liver metastases.

PMID- 18345301
TI  - Cystic tumours of the pancreas.
AB  - Pancreatic carcinoma accounts for the most dismal survival among all malignancies
      with 5-year survival rates approaching 5%. The reason for this, besides the
      inherent biologic nature of the disease, is the fact that the patients tend to
      present late in the disease. We present a review of the current published data on
      cystic neoplasms of the pancreas, which though rare, constitute an important
      subgroup of pancreatic neoplasms that have a better prognosis and are potentially
      curable lesions.

PMID- 18345302
TI  - A multicentre controlled study of the InLine radiofrequency ablation device for
      liver transection.
AB  - BACKGROUND: Surgical resection is the most effective therapy for liver cancer.
      Intraoperative blood loss during liver resection remains a major concern due to
      association with higher postoperative complications. The InLine radiofrequency
      ablation device (ILRFA) has achieved promising results in liver surgery with
      minimal blood loss and no increase of postoperative complications. In this
      multicentre controlled study, 108 patients undergoing liver resection were
      investigated. PATIENTS AND METHODS: A total of 108 patients underwent liver
      resections in 4 medical centres; the prospective sequential cohort study
      consisted of 54 ILRFA and 54 ultrasonic surgical aspirator transections as the
      control group. RESULTS: The type of liver resection performed was very similar in
      both groups. The median number of RFA deployments was 3 (range 1-12) with a
      median coagulation time of 9 (range 3-36) min. Median blood loss was 165+/-20 ml
      (range 5-675) in the ILRFA and 654+/-83 ml (range 80-3600) in the control group
      (p<0.001). The median transection time was 27 (2-219) min in the ILRFA group and
      35 (5-62) min in controls. CONCLUSIONS: Our study indicates that ILRFA device for
      liver transection is effective in reducing blood loss and is safe. Precoagulation
      before parenchymal transection appears to be a valid concept in liver surgery.
      The avoidance of vascular inflow occlusion during parenchymal transection could
      also be of value.

PMID- 18345303
TI  - Physician predictions of graft survival following liver transplantation.
AB  - INTRODUCTION: Due to the scarcity of cadaveric livers, clinical judgment must be
      used to avoid futile transplants. However, the accuracy of human judgment for
      predicting outcomes following liver transplantation is unknown. The study aim was
      to assess expert clinicians' ability to predict graft survival and to compare
      their performance to published survival models. MATERIALS AND METHODS: Pre
      transplant case summaries were prepared based on 16 actual, randomly selected
      liver transplants. Clinicians specializing in the care of liver transplant
      patients were invited to assess the likelihood of 90-day graft survival for each
      case using (1) a 4-point Likert scale ranging from poor to excellent, and (2) a
      visual analog scale denoting the probability of survival. Four published models
      were also used to predict survival for the 16 cases. RESULTS. Completed
      instruments were received from 50 clinicians. Prognostic estimates on the two
      scales were highly correlated (median r=0.88). Individual clinicians' predictive
      ability was 0.61+/-0.13, by area under the receiver operating characteristic
      curve. The performance of published models was MELD 0.59, Desai 0.66, Ghobrial
      0.61, and Thuluvath 0.45. For three cases, clinicians consistently overestimated
      the probability of survival (87+/-10%, 89+/-9%, 86+/-9%); these patients had
      early graft failures caused by postoperative complications. DISCUSSION.
      Clinicians varied in their ability to predict survival for a set of pre
      transplant scenarios, but performed similarly to published models. When
      clinicians overestimated the chance of transplant success, either sepsis or
      hepatic artery thrombosis was involved; such events may be hard to predict before
      surgery.

PMID- 18345304
TI  - Recent trends in liver resection surgery activity and population utilization
      rates in English regions.
AB  - OBJECTIVE: We conducted a study to examine recent trends in population-based
      utilization rates for liver resection surgery in England, to help identify
      potentially unmet healthcare need and to help inform future service planning.
      MATERIALS AND METHODS: Hospital Episodes Statistics data were analysed for the 5
      year period 2000-1 to 2004-5 to identify episodes of care relating to liver
      resection surgery (defined as OPSC IV codes J21 to J24, J31, J38 and J39).
      RESULTS: In England, the liver excision surgery population access rate was 1.82
      and 2.95/100,000 general population in 2000-1 and 2004-5, respectively--a 62%
      increase during the 5-year study period, or a mean 12% annual increase. About two
      thirds of all liver resection surgery (69%) related to metastatic liver disease.
      Between English regions, utilization rates ranged from 0.5 to 4.5/100,000 general
      population in 2000-1; and from 0.8 to 4.6/100 000 general population in 2004-5.
      DISCUSSION: In recent years, a rapid increase in liver resection surgery activity
      has been observed. Most of the activity was related to metastatic disease. There
      was substantial regional variation in population utilization rates within the
      same country. This variation is unlikely to represent regional differences in
      disease burden and healthcare need.

PMID- 18345305
TI  - Bile duct cyst type V (Caroli's disease): surgical strategy and results.
AB  - BACKGROUND: Caroli's disease (CD) is a benign congenital disorder characterized
      by segmental cystic dilatation of the intrahepatic biliary ducts. Therapeutic
      strategy includes medical treatment, percutaneous, endoscopic or surgical
      drainage of the affected bile ducts, liver resection or transplantation. The aim
      of this study was to analyse the results and long-term follow-up of a consecutive
      series of patients who underwent surgical treatment for CD. PATIENTS AND METHODS:
      Between 1995 and 2005, 10 patients were surgically treated for CD. Variables
      evaluated were: age, gender, clinical presentation, diagnostic procedures,
      percutaneous and surgical treatments, histopathological analysis and outcome.
      RESULTS: The average age of the patients was 45.8 years. Recurrent cholangitis
      was the main clinical manifestation (70%). In unilateral CD a liver resection was
      performed in nine patients (left lateral sectionectomy in seven, left hepatectomy
      in one and right hepatectomy in one). In bilateral disease a cholecystectomy,
      duct exploration, hepaticojejunostomy and liver biopsy of both lobes were
      performed. Average follow-up was 60 months. All the patients are alive and free
      of symptoms without recurrence in the remnant liver. DISCUSSION: Liver resection
      is the preferred therapeutic option for unilateral CD, demonstrating good results
      in long-term follow-up. In bilateral disease, hepaticojejunostomy could be
      considered as an alternative or a previous step to liver transplantation, which
      still remains the ultimate option.

PMID- 18345306
TI  - Is there a role for estrogen and progesterone receptors in gall bladder cancer?
AB  - BACKGROUND/AIMS: The concept of metaplastic and non-metaplastic types of gall
      bladder cancer and the likelihood of hormone receptor expression in the nuclei of
      tumour cells raised the possibility of a potential role for anti-estrogen therapy
      in gall bladder cancer. This study was carried out to determine the hormone
      receptors (ER/PR) expression level in gall bladder cancer using specific
      immunohistochemical assays and correlate it with patient and tumour
      histopathological characteristics. PATIENTS AND METHODS: Histopathological tumour
      specimens of 62 patients who underwent a radical cholecystectomy were analysed.
      Pronase pretreatment and primary monoclonal antibodies were used to perform
      immunohistochemical analysis for ER and PR. RESULTS: The histology was
      adenocarcinoma--predominantly, moderately to poorly differentiated (91%).
      Gallstones were present in 90% of the individuals. Of the 62 specimens analysed,
      62 (100%) and 61 (98%) were negative for ER and PR, respectively. CONCLUSION: The
      high incidence of gallstone-related gall bladder cancer in India is associated
      with metaplasia and a tendency to poorer differentiation in the tumour histology.
      These tumours are consequently less likely to express hormone receptors. Thus,
      there does not seem to be a role for anti-hormone therapy in patients with
      histogenesis similar to that seen in India.

PMID- 18345307
TI  - Interferon receptor alpha/beta is associated with improved survival after
      adjuvant therapy in resected pancreatic cancer.
AB  - AIM: Interferons (IFNs) are known to have antiproliferative and immunoregulatory
      activities that are modulated through specific cell surface ligands, known as IFN
      alpha, -beta, and -gamma receptors. The presence of these receptors and their
      impact on response to adjuvant therapy in patients with pancreatic cancer has not
      been determined. PATIENTS AND METHODS: Slides were prepared from 46 patients with
      pancreatic adenocarcinoma. Immunohistochemistry (IHC) was subsequently used to
      determine the expression of IFN- alpha/beta receptor-chain 2 (IFN-alpha/betaR)
      and IFN-gamma receptor-chain 1 (IFN-gammaR). The correlation between IFN receptor
      expression, tumor characteristics, and the overall patient response to adjuvant
      therapy were determined analytically. RESULTS: The IHC performed for pancreatic
      adenocarcinoma demonstrated a high IFN-alpha/betaR expression in 4% (2/46) of
      patients, moderate expression in 20% (9/46) of patients, and faint or no
      expression in 76% (35/46) of patients. IHC confirmed a high expression of IFN
      gammaR in 52% (24/46) of patients, moderate expression in 35% (16/46) of
      patients, and faint or no expression in the remaining 13% (6/46) of patients.
      Thirty-two (69.7%) patients received adjuvant therapy. Clinicopathological survey
      did not demonstrate any significant correlation between IFN-alpha/betaR and IFN
      gammaR expression with regard to tumor size, vascular invasion, perineural
      invasion, lymph node metastases, or stage of disease. Use of adjuvant therapy was
      associated with increased survival in patients with IFN-alpha/betaR-positive
      tumors compared with patients with IFN-alpha/betaR-negative tumors (24 months
      versus 14.7 months in log rank test, p=0.012). The expression of IFN-gammaR,
      however, had no impact on patient survival (20 months vs 17 months; p=0.656, log
      rank test). CONCLUSION: IFN-alpha/betaR is associated with improved survival for
      patients with resectable pancreatic cancer who received adjuvant therapy.

PMID- 18345308
TI  - Continuous veno-venous haemofiltration in the treatment of severe acute
      pancreatitis: 6-year experience.
AB  - BACKGROUND: Continuous veno-venous haemofiltration (CVVH) could be reasonable for
      attenuation of systemic complications in severe acute pancreatitis (SAP). The aim
      of the study was implementation and feasibility assessment of the CVVH in the
      treatment protocol of SAP. PATIENTS AND METHODS: CVVH was applied to 111 SAP
      patients during 2000-2005. APACHE II, systemic inflammatory response syndrome
      (SIRS), multiple organ dysfunction syndrome (MODS), serum lipase, C-reactive
      protein (CRP), complication rate and main outcomes were analysed comparing two
      periods. RESULTS: Overall, 39 patients corresponded to Balthazar grade E SAP and
      72 patients to necrotizing SAP (NSAP), with an average APACHE II score of 7 and
      8.5, respectively, on admission. CVVH was started within 48 h in 82% of patients.
      Duration of CVVH was significantly augmented in NSAP patients during the routine
      period, comprising 92 h (p=0.006). The clinical presentation of SIRS and MODS was
      similar in both periods, with more initial pulmonary dysfunctions in NSAP
      (p=0.048). Peripancreatic infection decreased in the routine period; surgical
      interventions were performed in 34.8% vs 72.4% of patients. Hospital stay
      comprised on average 15.9 days for grade E SAP and 29.4 days for NSAP in the
      routine period, with overall mortality of 10.26% and 30.5%, respectively.
      DISCUSSION: Application of CVVH in the treatment protocol of SAP is obscure due
      to relative invasiveness, a poorly understood mechanism of action and scarce
      clinical experience. We conclude that early pre-emptive application of CVVH is
      safe and feasible in the treatment of SAP. Duration of the procedure seems to be
      essential. Randomized clinical trials are justified. Our results are in favour of
      clinical application of CVVH in the treatment of SAP.

PMID- 18345309
TI  - Analysis of closure of the pancreatic remnant after distal pancreatic resection.
AB  - BACKGROUND: The appropriate management of the pancreatic remnant following distal
      pancreatic resection remains a clinically relevant problem. We carried out a
      retrospective analysis which focused on this issue and compared the two favored
      techniques of suture and staple closure. PATIENTS AND METHODS: Forty-six patients
      underwent distal pancreatectomy between October 1999 and January 2006. The
      patients were retrospectively analysed based on the management of the remaining
      pancreatic gland. Thirty-seven patients had suture and nine patients had staple
      closure. The morbidity, mortality, incidence of pancreatic fistula, necessity of
      secondary surgical intervention, and the duration of hospital stay for the two
      groups were compared. Pancreatic fistula was considered according to the novel
      international standard definition (ISGPF). In addition, subgroup analysis of
      patients receiving octreotide was carried out. RESULTS: Overall, postoperative
      morbidity due to pancreatic fistula occurred in seven patients (19%) after suture
      and in one patient (11%) after staple closure (p = 0.54), with no deaths. The
      number of patients with surgical revision related to pancreatic leakage was two
      (5%) after suture closure vs no revision after staple closure (p = 0.65). The
      median number of total hospital days for the suture group was 19 (range 7-78
      days) vs 21 (range 12-96 days) for the stapler group (p = 0.21). No significant
      benefit for the octreotide application could be determined. CONCLUSION: According
      to the data, no significant difference for either suture or stapler closure was
      observed, with the tendency for staple closure to be superior.

PMID- 18345310
TI  - Results of decompression surgery for pain in chronic pancreatitis.
AB  - INTRODUCTION: A vast majority of patients with chronic pancreatitis require
      regular opiate/opioid analgesia and recurrent hospital admission for pain.
      However, the role and timing of operative strategies for pain in chronic
      pancreatitis is controversial. This study hypothesized that pancreatic
      decompression surgery reduces analgesia requirement and hospital readmission for
      pain in selected patients. PATIENTS AND METHODS: This was a retrospective review
      of patients undergoing longitudinal pancreatico-jejunostomy (LPJ), with or
      without coring of the pancreatic head (Frey's procedure), between 1995 and 2007
      in a single UK centre. Surgery was performed for chronic pain with
      clinical/radiological evidence of chronic pancreatitis amenable to
      decompression/head coring. RESULTS: Fifty patients were identified. Thirty-six
      were male with a median age of 46 years and median follow-up of 30 months. Twenty
      eight underwent LPJ and 22 underwent Frey's procedure. No significant difference
      in reduction of analgesia requirement (71% vs 64%, p=0.761) or hospital
      readmission for pain (21% vs 23%, p=1.000) was observed when comparing LPJ and
      Frey's procedure. Patients were significantly more likely to be pain-free
      following surgery if they required non-opiate rather than opiate analgesia
      preoperatively (75% vs 19%, p=0.0002). Fewer patients required subsequent
      hospital readmission for pain if taking non-opiate rather than opiate analgesia
      preoperatively (12.5% vs 31%, p=0.175). CONCLUSIONS: In selected patients, LPJ
      and Frey's procedure have equivalent benefit in short-term pain reduction.
      Patients should be selected for surgery before the commencement of opiate
      analgesia.

PMID- 18345311
TI  - Nonalcoholic fatty pancreas disease.
AB  - BACKGROUND: Obesity leads to fat infiltration of multiple organs including the
      heart, kidneys, and liver. Under conditions of oxidative stress, fat-derived
      cytokines are released locally and result in an inflammatory process and organ
      dysfunction. In the liver, fat infiltration has been termed nonalcoholic fatty
      liver disease, which may lead to nonalcoholic steatohepatitis. No data are
      available, however, on the influence of obesity on pancreatic fat and cytokines,
      and nonalcoholic fatty pancreas disease (NAFPD) has not been described.
      Therefore, we designed a study to determine whether obesity is associated with
      increased pancreatic fat and cytokines. MATERIALS AND METHODS: Thirty C57BL/6J
      lean control and 30 leptin-deficient obese female mice were fed a 15% fat diet
      for 4 weeks. At 12 weeks of age all animals underwent total pancreatectomy.
      Pancreata from each strain were pooled for measurement of a) wet and dry weight,
      b) histologic presence of fat, c) triglycerides, free fatty acids (FFAs),
      cholesterol, phospholipids, and total fat, and d) interleukin (IL)-1beta and
      tumor necrosis factor-alpha (TNF-alpha). Data were analyzed by Student's t test
      and Fisher's exact test. RESULTS: Pancreata from obese mice were heavier (p<0.05)
      and had more fat histologically (p<0.05). Pancreata from obese mice had more
      triglycerides, FFAs, cholesterol, and total fat (p<0.05). Triglycerides
      represented 11% of pancreatic fat in lean mice compared with 67% of pancreatic
      fat in obese mice (p<0.01). Cytokines IL-1beta and TNF-alpha also were elevated
      in the pancreata of obese mice (p<0.05). CONCLUSIONS: These data suggest that
      obese mice have 1) heavier pancreata, 2) more pancreatic fat, especially
      triglycerides and FFAs, and 3) increased cytokines. We conclude that obesity
      leads to nonalcoholic fatty pancreatic disease.

PMID- 18345312
TI  - Use of radiofrequency hepatic parenchymal transection device in hepatic
      hemangioma resection: early experience and lessons learned.
AB  - BACKGROUND: Control of intraoperative hemorrhage represents a significant
      challenge in hepatic surgery, particularly during resection of large,
      hypervascular hepatic hemangiomata (HH). Various devices to minimize blood loss
      from hepatic parenchymal transection are currently under investigation. Herein,
      we present our experience with a radiofrequency (RF)-powered multiarray for
      resection of HH. PATIENTS AND METHODS: From September 2005 to January 2006, we
      conducted a retrospective review of our hepatobiliary database to identify
      patients with symptomatic giant cavernous HH undergoing resection with a RF
      multiarray device. The purpose of this review was to assess the technical aspects
      of using RF energy to assist in the resection of HH. RESULTS: The extent of
      operation varied depending on the size and location of the tumor. Two patients
      underwent two atypical subsectionectomies and two underwent trisectionectomies.
      The Habib sealer provided a safe and effective method for hepatic parenchymal
      transaction. No patients required blood transfusion, and no injuries to major
      biliary or vascular strictures were observed at 1 year follow-up. A seroma
      developed in one patient 6 months postoperatively, but was drained
      percutaneously. CONCLUSIONS: Hepatic parenchymal transection with the Habib
      sealer device is a feasible approach to resect HH. Further study is needed to
      objectively compare the efficacy of RF-assisted parenchymal transection with that
      of traditional parenchymal transection techniques.

PMID- 18345313
TI  - Quality in hepatobiliary surgery.

PMID- 18345314
TI  - Role of volume outcome data in assuring quality in HPB surgery.
AB  - Many studies have shown an association between both surgeon and hospital
      operative procedure volumes and outcomes, particularly operative mortality. It is
      also recognized that volume is only one of a number of factors, including 1)
      surgeon training and experience, and 2) hospital resources, organization, and
      processes of care, which can also influence outcomes. The Surgical Oncology
      Program at Cancer Care Ontario has included hospital volumes in a set of
      standards for the conduct of major pancreatic cancer surgery, along with
      recommendations for surgeon training and hospital resources, organization,
      support services, and processes of care to encourage regionalization of major HPB
      surgery. Cooperation with these recommendations was encouraged by the public
      reporting of mortality data and by an educational program directed at both
      surgeons and senior administrators in Ontario hospitals with the support of the
      provincial health ministry. The provincial mortality rate from major pancreatic
      cancer surgery has decreased by more than 50% since the introduction of this
      program.

PMID- 18345315
TI  - Assuring quality in HPB surgery--efficacy and safety.
AB  - Surgical innovations have made enormous contributions towards the welfare of
      patients when they have been appropriate, effective and applied with expertise
      and overall care. However, the potential for advancement and for harm of new
      surgical techniques, and the level of expertise necessary for their safe
      introduction, are not always immediately apparent. Furthermore, it is difficult
      and time-consuming to assess the efficacy and safety of new procedures in the
      clinical setting. In 1998 the Royal Australasian College of Surgeons established
      ASERNIP-S, the Australian Safety and Efficacy Register of New and Interventional
      Procedures-Surgical, to help ensure that new technologies that are being
      introduced are well proven in concept, are as safe and effective as possible, and
      are utilized with high levels of skill underpinned by the level of training.

PMID- 18345316
TI  - Hepatic resection using a bipolar vessel sealing device: technical and
      histological analysis.
AB  - INTRODUCTION: Blood loss and bile leakage are well-known risk factors for
      morbidity and mortality during liver resection. Bleeding usually occurs during
      parenchymal transection, and surgical technique should be considered an important
      factor in preventing intraoperative and postoperative complications. OBJECTIVE:
      Many approaches and devices have been developed to limit bleeding and bile
      leakage. The aim of the present study was to determine whether a bipolar vessel
      sealing device allows a safe and careful liver transection without routine inflow
      occlusion, achieving a satisfactory hemostasis and bile stasis, thus reducing
      blood loss and bile leak and related complications. PATIENTS AND METHODS: A total
      of 50 consecutive patients (24 males, 26 females, with a mean age of 57 years)
      underwent major and minor hepatic resections using a bipolar vessel sealing
      device. A clamp crushing technique followed by energy application was used to
      perform the parenchymal transection. Inflow occlusion was used when necessary to
      control blood loss but not as a routine. No other devices were applied to achieve
      hemostasis. RESULTS: The instrument was effective in 45 patients and failed to
      achieve hemostasis in 5 cases, all of whom had a cirrhotic liver. Median blood
      loss was 490 ml (range 100-2500 ml) and intraoperative blood transfusions were
      required in eight cases (16%). Mean operative time was 178 min (range 50-315
      min). Inflow occlusion was necessary in 16 (32%) patients. The postoperative
      complication rate was 24%, with a postoperative hemorrhage in a cirrhotic
      patient. There was no clinical evidence of bile leak or procedure-related
      abdominal abscess. CONCLUSION: We conclude that the device is a useful tool in
      standard liver resection, achieving good hemostasis and bile stasis in patients
      with normal liver parenchyma, but its use should be avoided in cirrhotic
      patients.

PMID- 18345317
TI  - Hepatic resection for metastatic gastrointestinal and pancreatic neuroendocrine
      tumours: outcome and prognostic predictors.
AB  - BACKGROUND: Treatment modalities for hepatic metastases from neuroendocrine
      tumours (NETs) include surgery, somatostatin analogues and arterial embolization.
      The aims of this study were to evaluate the outcome of patients following surgery
      and to identify prognostic predictors of recurrent disease. PATIENTS AND METHODS:
      This was a retrospective clinico-pathological analysis of patients managed with
      hepatic NET metastases over a 13-year period (January 1994 to December 2006).
      RESULTS: Eighteen patients with hepatic metastases from NET were identified with
      a median age of 53 years (range 31-75). The localization of the primary tumour
      was the terminal ileum (n=8), pancreas (n=7), appendix (n=2) or duodenum (n=1).
      Twelve patients had synchronous disease and six patients developed metachronous
      hepatic tumours over a median period of 20 months (range 6-144). Presenting
      symptoms included abdominal pain (n =13), recurrent diarrhoea (n=7) and flushing
      (n=7). Fifteen patients underwent surgery with complete cytoreduction and three
      patients had partial cytoreduction. The overall 2- and 5-year actuarial survival
      rates were 94% and 86%, respectively. The 2- and 5-year disease-free rates
      following hepatic resection with complete cytoreduction were both 66%. Partial or
      complete control of endocrine-related symptoms was achieved in all patients with
      functioning tumours following surgery. Recurrent disease occurred in four
      patients following complete cytoreductive surgery. Resection margin involvement
      was associated with developing recurrent disease (p=0.041). CONCLUSION: Surgical
      resection for hepatic NET metastases results in good long-term survival in
      selected patients and resection margin involvement was associated with recurrent
      disease.

PMID- 18345318
TI  - Liver transplantation in adult patients with portal vein thrombosis: risk
      factors, management and outcome.
AB  - BACKGROUND: Portal vein thrombosis (PVT) is a well recognized complication of
      patients with end-stage cirrhosis and its incidence ranges from 2 to 26%. The aim
      of this study was to analyze the results and long-term follow-up of a consecutive
      series of liver transplants performed in patients with PVT and compare them with
      patients transplanted without PVT. PATIENTS AND METHODS: Between July 1995 and
      June 2006, 26 liver transplants were performed in patients with PVT (8.7%). Risk
      factors and variables associated with the transplant and the post-transplant
      period were analyzed. A comparative analysis with 273 patients transplanted
      without PVT was performed. RESULTS: The patients comprised 53.8% males, average
      age 40, 7 years. PVT was detected during surgery in 65%. Indications for
      transplantation were: post-necrotic cirrhosis 73%, cholestatic liver diseases
      23%, and congenital liver fibrosis 4%. Child-Pugh C: 61.5%. Techniques were
      trombectomy in 21 patients with PVT grades I, II, IV, and extra-anatomical
      mesenteric graft in 5 with grade III. Morbidity was 57.7%, recurrence of PVT was
      7.7%, and in-hospital mortality was 26.9%. Greater operative time, transfusion
      requirements, and re-operations were found in PVT patients. One-year survival was
      59.6%: 75.2% for grade 1 and 44.8% for grades 2, 3, and 4. DISCUSSION: The study
      demonstrated a PVT prevalence of 8.7%, a higher incidence of partial thrombosis
      (grade 1), and successful management of PVT grade 4 with thrombectomy. Liver
      transplant in PVT patients was associated with an increased operative time,
      transfusion requirements, re-interventions, and lower survival rate according to
      PVT extension.

PMID- 18345319
TI  - Microwave ablation in a hepatic porcine model: correlation of CT and
      histopathologic findings.
AB  - BACKGROUND: Thermal ablative techniques have gained increasing popularity in
      recent years as safe and effective options for patients with unresectable solid
      malignancies. Microwave ablation has emerged as a relatively new technique with
      the promise of larger and faster burns without some of the limitations of
      radiofrequency ablation (RFA). Here we study a new microwave ablation device in a
      living porcine model using gross, histologic, and radiographic analysis.
      MATERIALS AND METHODS: The size and shape of ablated lesions were assessed using
      six pigs in a non-survival study. Liver tissue was ablated using 2, 4, and 8 min
      burns, in both peripheral and central locations, with and without vascular inflow
      occlusion. To characterize the post-ablation appearance, three additional pigs
      underwent several 4 min ablations each followed by serial computed tomography
      (CT) imaging at 7, 14, and 28 days postoperatively. RESULTS: The 2 and 4 min
      ablations resulted in lesions that were similar in size, 33.5 cm(3) and 37.5
      cm(3), respectively. Ablations lasting 8 min produced lesions that were
      significantly larger, 92.0 cm(3) on average. Proximity to hepatic vasculature and
      inflow occlusion did not significantly change lesion size or shape. In follow-up
      studies, CT imaging showed a gradual reduction in lesion volume over 28 days to
      25-50% of the original volume. DISCUSSION: Microwave ablation with a novel device
      results in consistently sized and shaped lesions. Importantly, we did not observe
      any significant heat-sink effect using this device, a major difference from RFA
      techniques. This system offers a viable alternative for creating fast, large
      ablation volumes for treatment in liver cancer.

PMID- 18345320
TI  - Evaluation of mulitprobe radiofrequency technology in a porcine model.
AB  - OBJECTIVE: We evaluated two new radiofrequency devices in an in vivo porcine
      model. MATERIALS AND METHODS: Multiprobe radiofrequency ablation (RFA) was used
      in a porcine model with an impedance-based algorithm in one experiment and
      clustered probes with and without switcher controllers in another; a Pringle
      maneuver was used with half of the ablations. RESULTS: The impedance experiment
      included 13 ablations, with a mean length of 7.0 cm and width of 2.9 cm (95% CI)
      and an average time of 596 s. Ablation volumes were significantly larger (54.1+/
      11.7 cc(3) vs 34.9+/-4.8 cc(3), p<0.05) and ablation times were significantly
      shorter (359 s vs 834 s, p<0.05) for the Pringle group compared with the No
      Pringle group, respectively. The switcher controller experiment included 34 RFAs.
      Diameter (mm) (51.4 vs 40.3, p<0.0001), surface area (cm(2)) (22.4 vs 16.0,
      p<0.0002), and volume (cc) (66.1 vs 36.9, p<0.0001) were significantly larger for
      the combination probes with switcher controller compared with clustered probes,
      respectively. Ablation volumes for the Pringle vs No Pringle groups in the
      combination probes were 68.0 cc vs 64.3 cc and for the clustered probes 40.1 cc
      vs. 33.7 cc, respectively. CONCLUSION: Multiprobe ablations using RFA are
      promising technologies that need further study to evaluate their clinical
      utility.

PMID- 18345321
TI  - Indication for treatment and long-term outcome of focal nodular hyperplasia.
AB  - INTRODUCTION: Unlike malignant liver tumours, the indications for hepatic
      resection for benign disease are not well defined. This is particularly true for
      focal nodular hyperplasia (FNH). Here we summarize a single-centre experience of
      the diagnosis and management of FNH. MATERIALS AND METHODS: Using a prospectively
      collected database, a retrospective analysis of consecutive patients who were
      managed at our centre for FNH between January 1997 and December 2006 was
      performed. RESULTS: The cohort was divided into two groups of patients: those who
      were managed surgically (n=15) and those managed conservatively (n=37). There was
      no correlation between tumour size and number of lesions with oral contraceptive
      use (p=0.07 and 0.90, respectively) and pregnancy (p=0.45 and 0.60,
      respectively). However, tumour size (p=0.006) and number of lesions (p=0.02) were
      associated with the occurrence of pain in these patients. Pain was the commonest
      symptom of patients (13/15) who were managed surgically. All patients underwent
      radiological imaging before diagnosis. The sensitivities of ultrasound, CT
      scanning and MRI scanning in characterizing these lesions were 30%, 70% and 87%,
      respectively. There were no postoperative deaths and three postoperative
      complications that were successfully managed non-operatively. With a median
      follow-up of 24 months in the surgically treated group, one patient has developed
      recurrent symptoms of pain. CONCLUSION. In this series, there was no mortality
      directly due to the surgical procedure and a modest morbidity, justifying
      surgical resections in selected patients.

PMID- 18345322
TI  - Differentiation between benign and malignant hilar obstructions using laboratory
      and radiological investigations: a prospective study.
AB  - BACKGROUND: Preoperative determination of the aetiology of bile duct strictures
      at the hilum is difficult. We evaluated the diagnostic accuracy of laboratory
      parameters and imaging modalities in differentiating between benign and malignant
      causes of hilar biliary obstruction. PATIENTS AND METHODS: Fifty-eight patients
      (26 men) with a history of obstructive jaundice and liver function tests (LFTs)
      and ultrasound suggestive of biliary obstruction at the hilum were studied. They
      were evaluated by tumour marker assay (CA19-9), CT and MRI/MRCP. A single
      experienced radiologist, blinded to the results of other tests, evaluated the
      imaging. The final diagnosis was made either from histology of the resected
      specimen, operative findings or image-guided biopsy in inoperable patients. A
      receiver operator characteristic (ROC) curve was constructed for each laboratory
      parameter to determine optimal diagnostic cut-off to predict malignant biliary
      stricture (MBS). RESULTS: In all, 34 patients had a benign and 24 had malignant
      aetiology. The mean age of benign patients was 38 years compared with 54 years
      for MBS. Forty-seven patients were treated with surgery while 11 had ERCP/PTC and
      stenting. The ROC curve showed that preoperative bilirubin level >8.4 mg/dl
      (sensitivity 83.3%, specificity 70%), alkaline phosphatase level >478 IU
      (sensitivity 63%, specificity 49%) and CA19-9 levels >100 U/L (sensitivity 45.8%,
      specificity 88.2%) for predicting MBS. The sensitivity, specificity and
      diagnostic accuracy of MRI/MRCP (87.5%, 85.3%, 82.7%, respectively) was
      marginally superior to CT (79.2%, 79.4%, 79.3%, respectively). CONCLUSIONS:
      Patients with a bilirubin level of >8.4 mg% and CA19-9 level >100 U/L were more
      likely to have malignant aetiology. MRI/MRCP was a better imaging modality than
      CT.

PMID- 18345323
TI  - Choledochal cysts: analysis of disease pattern and optimal treatment in adult and
      paediatric patients.
AB  - BACKGROUND: Choledochal cysts are dilations of the biliary tree. Although
      commonly reported in Asian populations, the incidence outside of Asia is as low
      as 1:150 000. The largest series of patients with choledochal cyst disease
      outside of Asia is this one, studying 70 patients treated in Vancouver between
      1971 and 2003. PATIENTS AND METHODS: This was a retrospective chart review.
      RESULTS: In all, 19 paediatric and 51 adult patients were evaluated; 21% of
      paediatric and 25% of adult patients were Asian. All paediatric patients had type
      I or IV cysts, whereas adult patients represented the different subtypes.
      Abdominal pain was the presenting symptom in 79% of children and 88% of adults,
      vomiting was present in 42% of children and 63% of adults and jaundice was seen
      in 31.5% of children and 39% of adults. Ultrasound was used in 94.7% of children,
      and ERCP in 80% of adults. In all, 84% of paediatric patients, 100% of adult
      patients with type I cysts and 85.7% of adult patients with type IV cysts
      received complete cyst excision and Roux-en-Y hepaticojejunostomy. Complications
      in both groups were low. CONCLUSIONS: Although Vancouver does have a large Asian
      population, this does not explain how common choledochal cysts are in this city.
      Although some authors argue that paediatric and adult disease are caused by
      different aetiologies, presentation patterns in our study between the two groups
      were very similar. We recommend complete cyst excision and Roux-en-Y
      hepaticojejunostomy as the surgery of choice, and advocate early surgery after
      diagnosis to promote ease of surgery and prevention of future complications.

PMID- 18345324
TI  - Improved lymph node retrieval in Whipple specimens as a result of implementation
      of a new uncinate margin protocol.
AB  - BACKGROUND: Lymph node status is an important prognostic factor in pancreatic and
      peri-ampullary adenocarcinoma. We recently changed our protocol for assessment of
      the uncinate margin of Whipple specimens and noted that lymph nodes were often
      present in uncinate margin sections. MATERIALS AND METHODS: Whipple specimens
      from 2004 to 2006 were divided into two groups, those that were handled according
      to the en face protocol, and those handled according to the radial protocol. The
      numbers of lymph nodes found in uncinate margin sections were assessed, as well
      as the total number of nodes found in the specimen. RESULTS: Sixteen cases were
      handled according to the en face protocol, and 20 according to the radial
      protocol. In the en face group, 2 benign nodes were found in the uncinate margin
      (0.1 nodes per case), while in the radial group, 36 nodes (1.8 nodes per case)
      were identified (p=0.0005). Eight cases in the latter group had positive nodes in
      the uncinate margin sections. In two of these cases the positive lymph node was
      the only lymph node with metastasis, and in an additional case the involved node
      was one of two positive lymph nodes. Total lymph node retrieval was 15.5 lymph
      nodes per case in the en face group, and 20 nodes per case in the radial group
      (p=0.02). DISCUSSION: The improved lymph node retrieval may be due to additional
      nodes found in radial sections of the uncinate margin, or alternatively, due to
      increased vigilance in specimen handling. In 3 of 20 cases, nodes found in the
      radial sections influenced staging.

PMID- 18345325
TI  - Effect of inhibition of prostaglandin E2 production on pancreatic infection in
      experimental acute pancreatitis.
AB  - OBJECTIVE: Acute pancreatitis is one the important causes of systemic
      inflammatory response syndrome (SIRS). SIRS results in gut barrier dysfunction
      that allows bacterial translocation and pancreatic infection to occur.
      Indomethacin has been used to reduce inflammatory process and bacterial
      translocation in experimental models. The purpose of this study was to determine
      the effect of inhibition of prostaglandin E2 (PGE2) production on pancreatic
      infection. MATERIALS AND METHODS: An experimental model of severe acute
      pancreatitis (AP) was utilized. The animals were divided into three groups: sham
      (surgical procedure without AP induction); pancreatitis (AP induction); and
      indomethacin (AP induction plus administration of 3 mg/kg of indomethacin). Serum
      levels of interleukin (IL)-6 and IL-10, PGE2, and tumor necrosis factor (TNF)
      alpha were measured 2 h after the induction of AP. We analyzed the occurrence of
      pancreatic infection with bacterial cultures performed 24 h after the induction
      of AP. The occurrence of pancreatic infection (considered positive when the CFU/g
      was >105), pancreatic histologic analysis, and mortality rate were studied.
      RESULTS: In spite of the reduction of IL-6, IL-10, and PGE2 levels in the
      indomethacin group, TNF-alpha level, bacterial translocation, and pancreatic
      infection were not influenced by administration of indomethacin. The inhibition
      of PGE2 production did not reduce pancreatic infection, histologic score, or
      mortality rate. CONCLUSION: The inhibition of PGE2 production was not able to
      reduce the occurrence of pancreatic infection and does not have any beneficial
      effect in this experimental model. Further investigations will be necessary to
      discover a specific inhibitor that would make it possible to develop an anti
      inflammatory therapy.

PMID- 18345326
TI  - Live demonstration of surgery across international borders with uncompressed high
      definition quality.
AB  - To provide more efficient medical education and clinical training opportunities,
      we report our first successful experience of uncompressed high-definition (HD)
      transmission of live surgery from Korea to Japan. Laparoscopic distal
      pancreatectomy was performed in Korea and broadcast to Fukuoka, Japan, at the
      venue of the First Biennial Congress of the Asian-Pacific Hepato-Pancreato
      Biliary Association (APHPBA) via super-fast broadband Internet on an academic
      fiber-optic network. The streaming of uncompressed HD images of live surgery was
      successfully performed with an interactive discussion between the two stations.
      The network remained stable throughout the session at as large a bandwidth as 1.6
      Gbps. With respect to HD image quality, 92% of respondents reported that it was
      'very good'. Use of this extraordinary high-quality image transmission will usher
      in a new era by providing much more accurate remote diagnosis and much better
      tele-education, not only in the field of hepato-pancreato-biliary surgery but
      also in many other fields of medicine.

PMID- 18345328
TI  - A new predictor for the onset of atrial fibrillation?

PMID- 18345329
TI  - N-terminal pro B-type natriuretic peptide levels predict newly detected atrial
      fibrillation in a population-based cohort.
AB  - BACKGROUND: B-type natriuretic peptide (BNP) is secreted from cardiomyocytes and
      may reflect haemodynamic abnormalities predisposing to atrial fibrillation (AF).
      We aimed to investigate whether N-terminal pro BNP (NT-proBNP) is associated with
      newly detected AF in subjects obtained from the general population. METHODS: From
      the PREVEND programme (n=8592), we selected all subjects with an available
      baseline and four-year electrocardiogram and NTproBNP levels at baseline. We
      excluded subjects with AF at baseline and subjects with a serum creatinine >2.0
      mg/dl. RESULTS: In total, 6494 subjects were eligible for the prospective
      analysis (aged 49+/-12 years, 49.7% men). At four years, AF was detected in 41
      (0.6%) subjects. Median NT-proBNP levels at baseline in subjects with newly
      detected AF after four years was 62.2 (22.6 to 208.5) pg/ml as compared with 35.7
      (15.9 to 68.7) pg/ml in those with sinus rhythm (p=0.001). Each 1 standard
      deviation increment in natural log transformed NT-proBNP was associated with a
      54% (5% to 126%, p=0.028) increase in risk for AF after adjustment for other risk
      factors predisposing to AF. NT-proBNP levels above the sex-specific 80th
      percentile (97 pg/ml in women and 60 pg/ml in men) were associated with a
      multivariate odds ratio of 2.65 (1.22 to 5.76, p=0.01) for the occurrence of AF.
      CONCLUSION: Plasma levels of NT-proBNP predict newly detected AF in subjects
      obtained from the general population independent of cardiovascular risk factors
      predisposing to AF. (Neth Heart J 2008;16:73-8.).

PMID- 18345330
TI  - Guidelines for heart transplantation.
AB  - Based on the changes in the field of heart transplantation and the treatment and
      prognosis of patients with heart failure, these updated guidelines were composed
      by a committee under the supervision of both the Netherlands Society of
      Cardiology and the Netherlands Association for Cardiothoracic surgery (NVVC and
      NVT).THE INDICATION FOR HEART TRANSPLANTATION IS DEFINED AS: 'End-stage heart
      disease not remediable by more conservative measures'.CONTRAINDICATIONS ARE:
      irreversible pulmonary hypertension/elevated pulmonary vascular resistance;
      active systemic infection; active malignancy or history of malignancy with
      probability of recurrence; inability to comply with complex medical regimen;
      severe peripheral or cerebrovascular disease and irreversible dysfunction of
      another organ, including diseases that may limit prognosis after heart
      transplantation.Considering the difficulties in defining end-stage heart failure,
      estimating prognosis in the individual patient and the continuing evolution of
      available therapies, the present criteria are broadly defined. The final
      acceptance is done by the transplant team which has extensive knowledge of the
      treatment of patients with advanced heart failure on the one hand and thorough
      experience with heart transplantation and mechanical circulatory support on the
      other hand. (Neth Heart J 2008;16:79-87.).

PMID- 18345331
TI  - Salade malade: malignant ventricular arrhythmias due to an accidental
      intoxication with Aconitum napellus.
AB  - Intoxication with Aconitum napellus is rare in our regions. Aconite alkaloids can
      cause ventricular arrhythmia by a prolonged activation of sodium channels.
      Because the margin of safety is low between the analgesic and toxic dose,
      intoxication is not rare when Aconite is used in herbal medicine. We present a
      case in which a 39-year-old male was accidentally intoxicated with Aconite. Even
      though no antidote or adequate therapy is available he was successfully
      resuscitated. (Neth Heart J 2008;16:96-9.).

PMID- 18345332
TI  - Acquired left coronary artery fistula to right ventricular outflow tract.

PMID- 18345333
TI  - Adrenergic regulation of conduction velocity in cultures of immature
      cardiomyocytes.
AB  - During cardiac maturation, increased exposure of the heart to circulating
      catecholamines correlates with increased conduction velocity and growth of the
      heart. We used an in vitro approach to study the underlying mechanisms of
      adrenergic stimulation induced changes in conduction velocity. By combining
      functional measurements and molecular techniques, we were able to demonstrate
      that the increased conduction velocity after beta-adrenergic stimulation is
      probably not caused by changes in intercellular coupling. Instead, RT-PCR
      experiments and action potential measurements have shown an increased
      excitability that may well explain the observed increase in conduction velocity.
      Apart from being relevant to cardiac maturation, our findings are relevant in the
      context of stem cells and cardiac repair. Preconditioning of stem cell derived
      cardiomyocytes may help to enhance electrical maturation of de novo generated
      cardiomyocytes and consequently reduce their proarrhythmogenic potential. (Neth
      Heart J 2008;16:106-9.).

PMID- 18345334
TI  - More precise classification of orthopaedic injury types and treatment will
      improve patient care.

PMID- 18345335
TI  - Concussion history and postconcussion neurocognitive performance and symptoms in
      collegiate athletes.
AB  - CONTEXT: Athletes are at an inherent risk for sustaining concussions. Research
      examining the long-term consequences of sport-related concussion has been
      inconsistent in demonstrating lingering neurocognitive decrements that may be
      associated with a previous history of concussion. OBJECTIVE: To determine the
      relationship between concussion history and postconcussion neurocognitive
      performance and symptoms in collegiate athletes. DESIGN: Repeated-measures
      design. SETTING: Multi-center analysis of collegiate athletes. PATIENTS OR OTHER
      PARTICIPANTS: Fifty-seven concussed collegiate athletes (36 without concussion
      history, 21 with a history of 2 or more concussions). INTERVENTION(S): All
      subjects were administered an Immediate Post-Concussion Assessment and Cognitive
      Testing (ImPACT) neurocognitive test battery, which measures verbal memory,
      visual memory, reaction time, and visual processing speed and 22 concussion
      symptoms. MAIN OUTCOME MEASURE(S): Subjects who sustained a concussion were
      administered 2 follow-up tests at days 1 and 5 postinjury. Independent variables
      were history of concussion (no history of concussion, 2 or more concussions) and
      time (baseline, day 1 postconcussion, or day 5 postconcussion). RESULTS: A within
      subjects effect (time) on ImPACT performance (P < .001), a between-subjects
      multivariate effect of group (P < .001), and a group-by-time interaction (P =
      .034) were noted. Athletes with a concussion history performed significantly
      worse on verbal memory (P = .01) and reaction time (P = .023) at day 5
      postconcussion compared with athletes who did not report a previous concussion.
      No significant group differences were seen at day 5 postinjury on visual memory
      (P = .167), processing speed (P = .179), or total concussion symptoms (P = .87).
      CONCLUSIONS: Concussed collegiate athletes with a history of 2 or more
      concussions took longer to recover verbal memory and reaction time than athletes
      without a history of concussion.

PMID- 18345336
TI  - Development of the mental, emotional, and bodily toughness inventory in
      collegiate athletes and nonathletes.
AB  - CONTEXT: The assessment of an individual's mental toughness would assist
      clinicians in enhancing an individual's performance, improving compliance with
      the rehabilitation program, and improving the individual treatment program.
      However, no sound measure of mental toughness exists. OBJECTIVE: To develop a new
      measure of mental toughness, the Mental, Emotional, and Bodily Toughness
      Inventory (MeBTough). DESIGN: Participants were invited to complete a 45-item
      questionnaire. SETTING: University research laboratory. PATIENTS OR OTHER
      PARTICIPANTS: A total of 261 undergraduate students were recruited to complete
      the questionnaire. MAIN OUTCOME MEASURE(S): The Rasch-calibrated item
      difficulties, fit statistics, and persons' mental toughness ability estimates
      were examined for model-data fit of the MeBTough. RESULTS: Forty-three of the 45
      items had good model-data fit with acceptable fit statistics. Results indicated
      that the distribution of items was fittingly targeted to the people and the
      collapsed rating scale functioned well. The item separation index (6.31) and
      separation reliability statistic (.98) provided evidence that the items had good
      variability with a high degree of confidence in replicating placement of the
      items from another sample. CONCLUSIONS: Results provided support for using the
      new measure of mental, emotional, and bodily toughness.

PMID- 18345337
TI  - Muscle activation during side-step cutting maneuvers in male and female soccer
      athletes.
AB  - CONTEXT: Female soccer athletes are at greater risk of anterior cruciate ligament
      (ACL) injury than males. Sex differences in muscle activation may contribute to
      the increased incidence of ACL injuries in female soccer athletes. OBJECTIVE: To
      examine sex differences in lower extremity muscle activation between male and
      female soccer athletes at the National Collegiate Athletic Association Division I
      level during 2 side-step cutting maneuvers. DESIGN: Cross-sectional with 1
      between-subjects factor (sex) and 2 within-subjects factors (cutting task and
      phase of contact). SETTING: Sports medicine research laboratory. PATIENTS OR
      OTHER PARTICIPANTS: Twenty males (age = 19.4 +/- 1.4 years, height = 176.5 +/-
      5.5 cm, mass = 74.6 +/- 6.0 kg) and 20 females (age = 19.8 +/- 1.1 years, height
      = 165.7 +/- 4.3 cm, mass = 62.2 +/- 7.2 kg). INTERVENTION(S): In a single testing
      session, participants performed the running-approach side-step cut and the box
      jump side-step cut tasks. MAIN OUTCOME MEASURE(S): Surface electromyographic
      activity of the rectus femoris, vastus lateralis, medial hamstrings, lateral
      hamstrings, gluteus medius, and gluteus maximus was recorded for each subject.
      Separate mixed-model, repeated-measures analysis of variance tests were used to
      compare the dependent variables across sex during the preparatory and loading
      contact phases of each cutting task. RESULTS: Females displayed greater vastus
      lateralis activity and quadriceps to hamstrings coactivation ratios during the
      preparatory and loading phases, as well as greater gluteus medius activation
      during the preparatory phase only. No significant differences were noted between
      the sexes for muscle activation in the other muscles analyzed during each task.
      CONCLUSIONS: The quadriceps-dominant muscle activation pattern observed in
      recreationally active females is also present in female soccer athletes at the
      Division I level when compared with similarly trained male soccer athletes. The
      relationship between increased quadriceps activation and greater incidence of
      noncontact ACL injury in female soccer athletes versus males requires further
      study.

PMID- 18345338
TI  - Triple-hop distance as a valid predictor of lower limb strength and power.
AB  - CONTEXT: Hop tests are functional tests that reportedly require strength, power,
      and postural stability to perform. The extent to which a triple-hop distance
      (THD) test measures each of these characteristics is relatively unknown.
      OBJECTIVE: To determine the extent to which the THD predicts performance on
      clinical measures of power, strength, and balance in athletic individuals.
      DESIGN: Within-subjects correlational study. SETTING: Station-based, preseason
      screening of athletes. PATIENTS OR OTHER PARTICIPANTS: Forty National Collegiate
      Athletic Association Division I-AA men's and women's soccer student-athletes (20
      women, 20 men; age = 20.0 +/- 1.4 years, height = 172.8 +/- 9.2 cm, mass = 71.9
      +/- 8.9 kg). INTERVENTION(S): As part of a comprehensive preseason screening of
      athletes, participants completed the Balance Error Scoring System (BESS) test, 3
      trials each of the THD and vertical jump, and 5 repetitions each of concentric
      isokinetic quadriceps and hamstrings strength testing at 60 degrees /s and 180
      degrees /s. Bivariate correlations and linear regression analyses determined the
      extent to which THD (cm) predicted each of the strength, power, and balance
      measures. MAIN OUTCOME MEASURE(S): Maximal vertical jump height (cm), total BESS
      error scores, and quadriceps (Quad(60), Quad(180)) and hamstrings (Ham(60),
      Ham(180)) isokinetic maximum peak torque (Nm) at 60 degrees /s and 180 degrees
      /s, respectively. RESULTS: Triple-hop distance was a strong predictor of vertical
      jump height, explaining 69.5% of the variance (P < .01). THD also predicted 56.7%
      of the variance in Ham(60) (P < .01), 55.5% of the variance in Ham(180) (P <
      .01), 49.0% of the variance in Quad(60) (P < .01), and 58.8% of the variance in
      Quad(180) (P < .01). No relationships between THD and BESS scores were noted.
      CONCLUSIONS: Triple-hop distance is a useful clinical test to predict an
      athlete's lower extremity strength and power. Although THD was not a predictor of
      static balance, further research is needed to examine its relationship with more
      dynamic balance tests.

PMID- 18345339
TI  - Fatigue and the electromechanical efficiency of the vastus medialis and vastus
      lateralis muscles.
AB  - CONTEXT: The relationship between the amplitudes of the mechanomyographic (MMG)
      and electromyographic (EMG) signals has been used to examine the
      "electromechanical efficiency" (EME) of normal and diseased muscle. The EME may
      help us to better understand the neuromuscular relationship between the vastus
      medialis and vastus lateralis muscles. OBJECTIVE: To examine the EME of the
      vastus medialis and vastus lateralis muscles during a fatiguing task. DESIGN:
      Repeated-measures design. SETTING: Research laboratory. PATIENTS OR OTHER
      PARTICIPANTS: Ten healthy males (age = 23.2 +/- 1.2 years) with no history of
      knee injury. INTERVENTION(S): Seventy-five consecutive, maximal concentric
      isokinetic leg extensions at a velocity of 180 degrees /s. MAIN OUTCOMES
      MEASURE(S): Bipolar surface EMG electrodes were placed over the vastus medialis
      and vastus lateralis muscles, with an MMG contact sensor placed adjacent to the
      superior EMG electrode on each muscle. The MMG and EMG amplitude values (root
      mean squares) were calculated for each of the 75 repetitions and normalized to
      the highest value from the 75 repetitions. The EME was expressed as the ratio of
      the log-transformed normalized MMG amplitude to the normalized EMG amplitude. For
      each muscle, the linear relationship for the normalized-group mean EME was
      determined across the 75 repetitions. RESULTS: Linear regression indicated
      decreases in torque (R(2) = .96), vastus medialis EME (R(2) = .73), and vastus
      lateralis EME (R(2) = .73). The slopes for the vastus medialis and vastus
      lateralis EME were not different (P > .10). CONCLUSIONS: The similarities in the
      fatigue-induced decreases in EME for the vastus medialis and vastus lateralis
      muscles suggested that symmetry was present between the muscles in the electric
      and mechanical responses to repeated, maximal muscle actions. The EME
      measurements may provide a unique insight into the influence of fatigue on the
      contractile properties of skeletal muscle, including alterations that occur to
      the intrinsic electric and mechanical components. The EME may be useful in
      assessing and quantifying clinically relevant asymmetries in vastus medialis and
      vastus lateralis muscle function in those with knee injuries.

PMID- 18345340
TI  - Bilateral medial tibiofemoral joint stiffness in full extension and 20 degrees of
      knee flexion.
AB  - CONTEXT: The valgus stress test is used clinically to assess injury to the medial
      knee structures in 2 positions: full extension and some degree of flexion. The
      amount of flexion used to "isolate" the medial collateral ligament is not
      consistent in the literature, but most studies have shown that stiffness of the
      ligaments was consistent between the limbs. OBJECTIVE: To determine (1) if the
      stiffness of the medial knee structures was the same bilaterally, and (2) if the
      stiffness was different in full extension compared with 20 degrees of knee
      flexion. DESIGN: Criterion standard, before-after design. SETTING: University
      research laboratory. PATIENTS OR OTHER PARTICIPANTS: Both knees of 45 healthy and
      active volunteers (26 females, 19 males; age = 23.2 +/- 3.96 years, height =
      170.6 +/- 7.75 cm, mass = 74.2 +/- 15.14 kg) were studied. INTERVENTION(S): A
      valgus force of 60 N was applied to the lateral aspect of both knees in full
      extension and in 20 degrees of flexion. MAIN OUTCOME MEASURE(S): The slope of the
      force-strain line of the medial knee during a valgus force was calculated using
      the LigMaster arthrometer. RESULTS: Slope means in full extension were 16.1 +/-
      3.3 (right knee) and 15.8 +/- 3.1(left knee). Means for 20 degrees of flexion
      were 12.2 +/- 3.1 (right) and 11.7 +/- 2.8 (left). Stiffness was greater when the
      knee was in full extension versus 20 degrees of flexion (t(44) = 12.04, P <
      .001). No difference was noted between the slopes of the 2 knees in extension
      (t(44) = 0.74, P = .46) or in flexion (t(44) = 1.2, P = .27). CONCLUSIONS: These
      findings support the use of the contralateral knee as a control. Further, the
      valgus stress test should be performed in full extension and in some degree of
      flexion to assess the different restraining structures of the medial tibiofemoral
      joint.

PMID- 18345341
TI  - Ankle bracing, fatigue, and time to stabilization in collegiate volleyball
      athletes.
AB  - CONTEXT: Fatigue has been shown to disrupt dynamic stability in healthy
      volunteers. It is not known if wearing prophylactic ankle supports can improve
      dynamic stability in fatigued athletes. OBJECTIVE: To determine the type of ankle
      brace that may be more effective at providing dynamic stability after a jump
      landing task during normal and fatigued conditions. DESIGN: Two separate repeated
      measures analyses of variance with 2 within-subjects factors (condition and time)
      were performed for each dependent variable. SETTING: Research laboratory.
      PATIENTS OR OTHER PARTICIPANTS: Ten healthy female collegiate volleyball athletes
      participated (age = 19.5 +/- 1.27 years, height = 179.07 +/- 7.6 cm, mass = 69.86
      +/- 5.42 kg). INTERVENTION(S): Athletes participated in 3 separate testing
      sessions, applying a different bracing condition at each session: no brace (NB),
      Swede-O Universal lace-up ankle brace (AB), and Active Ankle brace (AA). Three
      trials of a jump-landing task were performed under each condition before and
      after induced functional fatigue. The jump-landing task consisted of a single-leg
      landing onto a force plate from a height equivalent to 50% of each participant's
      maximal jump height and from a starting position 70 cm from the center of the
      force plate. MAIN OUTCOME MEASURE(S): Time to stabilization in the anterior
      posterior (APTTS) and medial-lateral (MLTTS) directions. RESULTS: For APTTS, a
      condition-by-time interaction existed (F(2,18) = 5.55, P = .013). For the AA
      condition, Tukey post hoc testing revealed faster pretest (2.734 +/- 0.331
      seconds) APTTS than posttest (3.817 +/- 0.263 seconds). Post hoc testing also
      revealed that the AB condition provided faster APTTS (2.492 +/- 0.271 seconds)
      than AA (3.817 +/- 0.263 seconds) and NB (3.341 +/- 0.339 seconds) conditions
      during posttesting. No statistically significant findings were associated with
      MLTTS. CONCLUSIONS: Fatigue increased APTTS for the AA condition. Because the AB
      condition was more effective than the other 2 conditions during the posttesting,
      the AB appears to be the best option for providing dynamic stability in the
      anterior-posterior direction during a landing task.

PMID- 18345342
TI  - Subtalar joint position during gastrocnemius stretching and ankle dorsiflexion
      range of motion.
AB  - CONTEXT: Gastrocnemius stretching exercises often are prescribed as part of the
      treatment program for patients with overuse injuries associated with limited
      ankle dorsiflexion. However, little is known about how the position of the
      subtalar joint during gastrocnemius stretching affects ankle dorsiflexion range
      of motion (ROM). OBJECTIVE: To determine the effect of subtalar joint position
      during gastrocnemius stretching on ankle dorsiflexion ROM. DESIGN: This study was
      a 3-way mixed-model design. The 3 factors were subtalar joint position
      (supinated, pronated), lower extremity (experimental, control), and time
      (pretest, posttest). Lower extremity and time were the repeated measures.
      SETTING: University research laboratory. PATIENTS OR OTHER PARTICIPANTS: Thirty
      three healthy volunteers (29 women, 4 men). INTERVENTION(S): Participants
      performed a gastrocnemius stretching exercise 2 times daily for 3 weeks with the
      subtalar joint of the randomly assigned experimental side (dominant or
      nondominant) in the randomly assigned position (supination or pronation). The
      contralateral lower extremity served as the control. MAIN OUTCOME MEASURE(S):
      Before and after the 3-week gastrocnemius stretching program, we used goniometers
      to measure ankle dorsiflexion ROM in weight-bearing and non-weight-bearing
      positions with the subtalar joint positioned in anatomic 0 degrees . RESULTS:
      Ankle dorsiflexion ROM measured in weight-bearing and non-weight-bearing
      positions increased after the gastrocnemius stretching program (P = .034 and
      .003, respectively), but the increase in ROM did not differ based on subtalar
      joint position (P = .775 and .831, respectively). CONCLUSIONS: Subtalar joint
      position did not appear to influence gains in ankle dorsiflexion ROM after a
      gastrocnemius stretching program in healthy volunteers.

PMID- 18345343
TI  - Validity of the Foot and Ankle Ability Measure in athletes with chronic ankle
      instability.
AB  - CONTEXT: The Foot and Ankle Ability Measure (FAAM) is a region-specific, non
      disease-specific outcome instrument that possesses many of the clinimetric
      qualities recommended for an outcome instrument. Evidence of validity to support
      the use of the FAAM is available in individuals with a wide array of ankle and
      foot disorders. However, additional evidence to support the use of the FAAM for
      those with chronic ankle instability (CAI) is needed. OBJECTIVE: To provide
      evidence of construct validity for the FAAM based on hypothesis testing in
      athletes with CAI. DESIGN: Between-groups comparison. SETTING: Athletic training
      room. PATIENTS OR OTHER PARTICIPANTS: Thirty National Collegiate Athletic
      Association Division II athletes (16 men, 14 women) from one university. MAIN
      OUTCOME MEASURE(S): The FAAM including activities of daily living (ADL) and
      sports subscales and the global and categorical ratings of function. RESULTS: For
      both the ADL and sports subscales, FAAM scores were greater in healthy
      participants (100 +/- 0.0 and 99 +/- 3.5, respectively) than in subjects with CAI
      (88 +/- 7.7 and 76 +/- 12.7, respectively; P < .001). Similarly, for both ADL and
      sports subscales, FAAM scores were greater in athletes who indicated that their
      ankles were normal (98 +/- 6.3 and 96 +/- 6.9, respectively) than in those who
      classified their ankles as either nearly normal or abnormal (87 +/- 6.6 and 71 +/
      11.1, respectively; P < .001). We found relationships between FAAM scores and
      self-reported global ratings of function for both ADL and sports subscales.
      Relationships were stronger when all athletes, rather than just those with CAI,
      were included in the analyses. CONCLUSIONS: The FAAM may be used to detect self
      reported functional deficits related to CAI.

PMID- 18345344
TI  - Sweat rates and fluid turnover in professional football players: a comparison of
      National Football League linemen and backs.
AB  - CONTEXT: Many National Football League (NFL) teams practice 2 times per day over
      consecutive days in a hot and humid environment. Large body surface area (BSA)
      and use of protective equipment result in high sweat rates and total sweat loss
      in these football players. OBJECTIVE: To compare sweat rate, sweat loss, fluid
      consumption, and weight loss between NFL linemen and backs during preseason
      practices. DESIGN: Between-groups design. SETTING: Preseason training camp with
      wet bulb globe temperature between 19 degrees C and 25 degrees C. PATIENTS OR
      OTHER PARTICIPANTS: Eight linemen and 4 backs and receivers participated. MAIN
      OUTCOME MEASURE(S): Data were collected during both practice sessions on 2
      separate days during the first week of August. Sweat rate was calculated as
      change in mass adjusted for all fluids consumed between prepractice and
      postpractice body mass measurements and the urine produced during practice
      divided by the length of the practice session. Gross daily sweat losses also were
      calculated. RESULTS: Height, mass, and BSA were higher in linemen than in backs.
      Sweat rate was also higher in linemen (2385 +/- 520 mL/h) than in backs (1410 +/-
      660 mL/h, P < .001), as was the total volume of sweat lost during both practices
      in 1 day (6870 +/- 1034 mL/d versus 4110 +/- 2287 mL/d, P = .014). Compared with
      backs, linemen consumed more fluids during practice (2030 +/- 849 mL versus 1179
      +/- 753 mL, P = .025) but produced less urine (53 +/- 73 mL versus 163 +/- 141
      mL, P = .018). There was no difference in postpractice weight loss (linemen = 
      1.15 +/- 0.83%, backs = -1.06 +/- 0.76%). CONCLUSIONS: Linemen sweated at higher
      rates, lost larger volumes of sweat, consumed more fluids, and produced less
      urine during practice compared with the physically smaller backs, but they did
      not lose a greater percentage of body weight. Sodium losses could be considerable
      in NFL players during the preseason because of high daily sweat losses in backs
      and in linemen.

PMID- 18345345
TI  - The diagnostic value of the Clarke sign in assessing chondromalacia patella.
AB  - CONTEXT: Various techniques have been described for assessing conditions that
      cause pain at the patellofemoral (PF) joint. The Clarke sign is one such test,
      but the diagnostic value of this test in assessing chondromalacia patella is
      unknown. OBJECTIVE: To (1) investigate the diagnostic value of the Clarke sign in
      assessing the presence of chondromalacia patella using arthroscopic examination
      of the PF joint as the "gold standard," and (2) provide a historical perspective
      of the Clarke sign as a clinical diagnostic test. DESIGN: Validation study.
      SETTING: All patients of one of the investigators who had knee pain or injuries
      unrelated to the patellofemoral joint and were scheduled for arthroscopic surgery
      were recruited for this study. PATIENTS OR OTHER PARTICIPANTS: A total of 106
      otherwise healthy individuals with no history of patellofemoral pain or
      dysfunction volunteered. MAIN OUTCOME MEASURE(S): The Clarke sign was performed
      on the surgical knee by a single investigator in the clinic before surgery. A
      positive test was indicated by the presence of pain sufficient to prevent the
      patient from maintaining a quadriceps muscle contraction against manual
      resistance for longer than 2 seconds. The preoperative result was compared with
      visual evidence of chondromalacia patella during arthroscopy. RESULTS:
      Sensitivity was 0.39, specificity was 0.67, likelihood ratio for a positive test
      was 1.18, likelihood ratio for a negative test was 0.91, positive predictive
      value was 0.25, and negative predictive value was 0.80. CONCLUSIONS: Diagnostic
      validity values for the use of the Clarke sign in assessing chondromalacia
      patella were unsatisfactory, supporting suggestions that it has poor diagnostic
      value as a clinical examination technique. Additionally, an extensive search of
      the available literature for the Clarke sign reveals multiple problems with the
      test, causing significant confusion for clinicians. Therefore, the use of the
      Clarke sign as a routine part of a knee examination is not beneficial, and its
      use should be discontinued.

PMID- 18345346
TI  - An epidemiologic comparison of high school sports injuries sustained in practice
      and competition.
AB  - CONTEXT: More than 7 million US high school students play sports. OBJECTIVE: To
      compare practice and competition injury rates and patterns in 5 boys' sports
      (football, soccer, basketball, wrestling, and baseball) and 4 girls' sports
      (soccer, volleyball, basketball, and softball) during the 2005-2006 school year.
      DESIGN: Prospective injury surveillance study. SETTING: Injury data were
      collected from 100 nationally representative United States high schools via High
      School RIO (Reporting Information Online). PATIENTS OR OTHER PARTICIPANTS:
      Athletes from participating high schools injured while participating in a school
      sanctioned practice or competition in one of the above sports. MAIN OUTCOME
      MEASURE(S): Practice and competition injury rates, body site, diagnosis, and
      severity. RESULTS: High school athletes participating in these 9 sports at
      participating schools sustained 4350 injuries during the 2005-2006 school year,
      which corresponds to an estimated 1 442 533 injuries nationally. The rate of
      injury per 1000 athlete-exposures was higher in competition (4.63) than in
      practice (1.69) (rate ratio [RR] = 2.73, 95% confidence interval [CI] = 2.58,
      2.90). Of all sports, football had the highest competition (12.09) and practice
      (2.54) injury rates per 1000 athlete-exposures. Compared with injuries sustained
      during practice, higher proportions of competition injuries were head/face/neck
      injuries (proportion ratio [PR] = 1.61, 95% CI = 1.34, 1.94), particularly in
      boys' soccer (PR = 7.74, 95% CI = 2.53, 23.65) and girls' basketball (PR = 6.03,
      95% CI = 2.39, 15.22). Competition injuries were more likely to be concussions
      (PR = 2.02, 95% CI = 1.56, 2.62), especially in boys' soccer (PR = 6.94, 95% CI =
      2.01, 23.95) and girls' basketball (PR = 5.83, 95% CI = 2.06, 16.49). Higher
      proportions of competition injuries caused the athlete to miss more than 3 weeks
      of play (PR = 1.28, 95% CI = 1.08, 1.52), particularly in baseball (PR = 3.47,
      95% CI = 1.48, 8.11) and volleyball (PR = 2.88, 95% CI = 1.01, 8.24).
      CONCLUSIONS: Rates and patterns of high school sport injuries differed between
      practice and competition. Providing athletic trainers with this information is a
      crucial step in developing the targeted, evidence-based interventions required to
      effectively reduce injury rates among the millions of high school student
      athletes.

PMID- 18345347
TI  - Individual moral philosophies and ethical decision making of undergraduate
      athletic training students and educators.
AB  - CONTEXT: Ethics research in athletic training is lacking. Teaching students
      technical skills is important, but teaching them how to reason and to behave in a
      manner that befits responsible health care professionals is equally important.
      OBJECTIVE: To expand ethics research in athletic training by (1) describing
      undergraduate athletic training students' and educators' individual moral
      philosophies and ethical decision-making abilities and (2) investigating the
      effects of sex and level of education on mean composite individual moral
      philosophies and ethical decision-making scores. DESIGN: Stratified, multistage,
      cluster-sample correlational study. SETTING: Mailed survey instruments were
      distributed in classroom settings at 30 institutions having Commission on
      Accreditation of Allied Health Education Programs (CAAHEP)-accredited athletic
      training programs. PATIENTS OR OTHER PARTICIPANTS: Undergraduate students and
      educators (n = 598: 373 women, 225 men; mean age = 23.5 +/- 6.3 years) from 25
      CAAHEP-accredited athletic training programs. MAIN OUTCOME MEASURE(S): We used
      the Ethics Position Questionnaire and the Dilemmas in Athletic Training
      Questionnaire to compute participants' mean composite individual moral
      philosophies (idealism and relativism) and ethical decision-making scores,
      respectively. Three separate 2 (sex: male, female) x 3 (education level:
      underclass, upper class, educator) between-subjects factorial analyses of
      variance using idealism, relativism, and ethical decision-making scores as
      dependent measures were performed. RESULTS: Respondents reported higher idealism
      scores (37.57 +/- 4.91) than relativism scores (31.70 +/- 4.80) (response rate =
      83%). The mean ethical decision-making score for all respondents was 80.76 +/-
      7.88. No significant interactions were revealed. The main effect for sex
      illustrated that men reported significantly higher relativism scores ( P = .0014,
      eta (2) = .015) than did women. The main effect for education level revealed
      significant differences between students' and educators' idealism ( P = .0190,
      eta (2) = .013), relativism ( P < .001, eta (2) = .050), and ethical decision
      making scores ( P < .001, eta (2) = .027). Tukey honestly significant difference
      post hoc analysis indicated that educators possessed lower idealism scores (36.90
      +/- 5.70) and relativism scores (29.92 +/- 4.86) and higher ethical decision
      making scores (82.98 +/- 7.62) than did students. CONCLUSIONS: Our findings do
      not support changes in athletic training ethics education practices to address
      sex-specific needs. However, when opportunities occur for students to reason
      using different ethical perspectives, educators should be aware of their
      students' and their own moral philosophies in order to optimally facilitate
      professional growth.

PMID- 18345348
TI  - Issues in outcomes research: an overview of randomization techniques for clinical
      trials.
AB  - OBJECTIVE: To review and describe randomization techniques used in clinical
      trials, including simple, block, stratified, and covariate adaptive techniques.
      BACKGROUND: Clinical trials are required to establish treatment efficacy of many
      athletic training procedures. In the past, we have relied on evidence of
      questionable scientific merit to aid the determination of treatment choices.
      Interest in evidence-based practice is growing rapidly within the athletic
      training profession, placing greater emphasis on the importance of well-conducted
      clinical trials. One critical component of clinical trials that strengthens
      results is random assignment of participants to control and treatment groups.
      Although randomization appears to be a simple concept, issues of balancing sample
      sizes and controlling the influence of covariates a priori are important. Various
      techniques have been developed to account for these issues, including block,
      stratified randomization, and covariate adaptive techniques. ADVANTAGES: Athletic
      training researchers and scholarly clinicians can use the information presented
      in this article to better conduct and interpret the results of clinical trials.
      Implementing these techniques will increase the power and validity of findings of
      athletic medicine clinical trials, which will ultimately improve the quality of
      care provided.

PMID- 18345349
TI  - Tissue adhesives for simple traumatic lacerations.
AB  - REFERENCE/CITATION: Farion K, Osmond MH, Hartling L, et al. Tissue adhesives for
      traumatic lacerations in children and adults. Cochrane Database Syst Rev.
      2001(4);CD003326. CLINICAL QUESTION: What is the clinical evidence base for
      tissue adhesives in the management of simple traumatic lacerations? DATA SOURCES:
      Studies were identified by searches of the following databases: Cochrane Wounds
      Group Specialized Trials Register (September 2003), Cochrane Central Register of
      Controlled Trials (CENTRAL) (CDROM 2003, issue 3), MEDLINE (1966 to September
      2003, week 1), EMBASE (1988 to 2003, week 36), Web of Science Science Citation
      Index (1975 to September 13, 2003) and various clinical trials registers
      (September 2003). Investigators and product manufacturers were contacted to
      identify additional eligible studies. The search terms included wounds and
      injuries, laceration, face injury, nose injury, tissue adhesives, and acrylates.
      STUDY SELECTION: Each study fulfilled the following criteria: (1) The study was a
      randomized controlled trial that compared tissue adhesives with standard wound
      closure (SWC) (sutures, staples, adhesive strips) or tissue adhesive with tissue
      adhesive. (2) The wounds were acute, linear lacerations less than 12 hours old,
      resulting from blunt or sharp trauma. (3) The wound length, width, and depth
      allowed for approximation of the edges with minimal tension after deep sutures
      were placed, if required. Studies were included with no language or publication
      status restriction, with participants of any age recruited in an emergency
      department, outpatient clinic, walk-in clinic, or other primary care setting.
      Studies were excluded if the wounds were stellate lacerations, puncture wounds,
      mammalian bites, infected, heavily contaminated or devitalized, crossing joints
      or mucocutaneous junctions, in hair-bearing areas, or in patients with keloid
      formation or chronic illness. DATA EXTRACTION: The characteristics of the study
      and participants, interventions, outcome measures, and findings were extracted by
      one author and verified by a second using a standard form. The primary measure
      was cosmetic outcome. Secondary measures were pain with the procedure, time to
      complete the procedure, and complications (erythema, infection, discharge, need
      for delayed closure, and dehiscence). Studies were divided into 2 groups as
      follows: group 1, comparisons among tissue adhesives with SWC, and group 2,
      comparisons among different tissue adhesives. All eligible studies were assessed
      for methodologic quality independently by 2 investigators using the Jadad Scale,
      which evaluates randomization, double blinding, withdrawals, and dropouts and is
      scored on a 5-point (maximum) scale. The data from the tissue adhesive and SWC
      studies were pooled and analyzed with a random-effects model. The I (2) statistic
      was used to determine heterogeneity among the studies. chi (2) analysis was
      performed to compare participant age, wound location, and type of tissue adhesive
      among the studies. The data from the studies comparing tissue adhesives were
      pooled and analyzed using a fixed-effects model. MAIN RESULTS: The search
      criteria identified 39 eligible studies, of which 11 met the inclusion criteria.
      In 10 studies, a tissue adhesive was compared with SWC. Five groups used
      butylcyanoacrylate, and 5 used octylcyanoacrylate. For SWC, 6 groups used
      sutures, 2 used adhesive strips, and 2 used a combination of methods, although
      most used sutures. Six studies were limited to pediatric patients and 2 to adult
      patients; 2 included patients of any age. Wounds were limited to facial
      lacerations in 2 pediatric studies and 1 group with patients of any age.
      Lacerations requiring deep sutures were excluded in 4 studies. One group compared
      tissue adhesives (butylcyanoacrylate and octylcyanoacrylate) among pediatric
      patients with facial lacerations not requiring deep sutures. In the 11 included
      studies, authors of 9 randomized and evaluated 1 laceration per patient, whereas
      2 groups included patients with more than 1 laceration. In 1 group, each
      laceration was independently randomized and evaluated, and the other group
      randomized the patient and assigned all lacerations to a treatment group (tissue
      adhesive with SWC or tissue adhesive with tissue adhesive). The sample sizes
      ranged between 60 and 163 lacerations, and all 11 studies were performed in
      emergency departments. The primary measure in all included studies was cosmetic
      outcome. The majority of groups used the Cosmetic Visual Analogue Scale, the
      Wound Evaluation Score, or a combination of these measures. Three groups measured
      cosmetic outcome with nonvalidated scoring systems. Assessment time periods were
      grouped and reported at (1) 5 to 14 days, (2) 1 to 3 months, and (3) 9 to 12
      months after wound closure. Secondary outcomes were pain (as noted on visual
      analogue scale) and time to complete the procedure (as mean number of minutes).
      The 11 studies scored from 1 to 3 on the Jadad Scale. Adequate allocation
      concealment was reported in only 1 group. Examining cosmetic outcome, 8 groups
      (565 lacerations) used the Cosmetic Visual Analogue Scale to compare tissue
      adhesives and SWC. The authors reported no significant differences in scores at
      the time periods of 5 to 14 days, 1 to 3 months, and 9 to 12 months. A subgroup
      analysis showed a significant ( P = .005) superiority of butylcyanoacrylate over
      SWC at 1 to 3 months. Using the Wound Evaluation Score, 4 studies (364
      lacerations) compared tissue adhesives with SWC. No significant differences in
      cosmetic scores were found at 5 to 14 days, 1 to 3 months, or 9 to 12 months. One
      group (83 lacerations) compared butylcyanoacrylate with octylcyanoacrylate and
      reported no significant differences in cosmetic scores using the Cosmetic Visual
      Analogue Scale at 1 to 3 months and the Wound Evaluation Score at 5 to 14 days
      and 1 to 3 months. Examining secondary outcomes, 6 groups (570 lacerations)
      compared tissue adhesives with SWC using the visual analogue scale for pain.
      Scores reported by parents, patients, physicians, and nurses significantly
      favored tissue adhesives. In 6 studies (584 lacerations), tissue adhesives were
      significantly favored over SWC in time to complete the procedure. For
      complication outcomes, 8 groups (727 lacerations) demonstrated significantly
      fewer incidences of erythema and an increased risk of dehiscence with tissue
      adhesives compared with SWC. No significant differences were shown for infection,
      delayed closure, or discharge. Among 83 lacerations, 1 group compared
      butylcyanoacrylate with octylcyanoacrylate and reported no significant
      differences in combined patient-reported and parent-reported visual analogue pain
      scores, time to complete the procedure, dehiscence, or infection. CONCLUSIONS:
      This review provides evidence that tissue adhesives are an option to SWC
      (sutures, staples, adhesive strips) for the management of simple traumatic
      lacerations. Overall, no significant differences were found in cosmetic scores at
      the reported assessment periods between tissue adhesives and SWC. At 1 to 3
      months, a subgroup analysis significantly favored butylcyanoacrylate over SWC.
      Tissue adhesives significantly lowered the time to complete the procedure, levels
      of pain, and rate of erythema. However, the data revealed a significant increase
      in the rate of dehiscence with the use of tissue adhesives when compared with
      SWC. The low methodologic quality of the evidence should be considered in the
      interpretation of the findings.

PMID- 18345351
TI  - Added astroglia promote greater synapse density and higher activity in neuronal
      networks.
AB  - Astroglia are known to potentiate individual synapses, but their contribution to
      networks is unclear. Here we examined the effect of adding either astroglia or
      media conditioned by astroglia on entire networks of rat hippocampal neurons
      cultured on microelectrode arrays. Added astroglia increased spontaneous spike
      rates nearly two-fold and glutamate-stimulated spiking by six-fold, with
      desensitization eliminated for bath addition of 25 microM glutamate. Astrocyte
      conditioned medium partly mimicked the effects of added astroglia. Bursting
      behavior was largely unaffected by added astroglia except with added glutamate.
      Addition of the GABA(A) receptor antagonist bicuculline also increased spike
      rates but with more subtle differences between networks without or with added
      astroglia. This indicates that networks without added astroglia were inhibited
      greatly. In all conditions, the log-log distribution of spike rates fit well to
      linear distributions over three orders of magnitude. Networks with added
      astroglia shifted consistently toward higher spike rates. Immunostaining for GFAP
      revealed a linear increase with added astroglia, which also increased neuronal
      survival. The increased spike rates with added astroglia correlated with a 1.7
      fold increase in immunoreactive synaptophysin puncta, and increases of six-fold
      for GABA(Abeta), two-fold for NMDA-R1 and two-fold for Glu-R1 puncta, with
      receptor clustering that indicated synaptic scaling. Together, these results
      indicate that added astroglia increase the density of synapses and receptors, and
      facilitate higher spike rates for many elements in the network. These effects are
      reproduced by glia-conditioned media, with the exception of glutamate-mediated
      transmission.

PMID- 18345352
TI  - Co-evolutionary rates of functionally related yeast genes.
AB  - Evolutionary knowledge is often used to facilitate computational attempts at gene
      function prediction. One rich source of evolutionary information is the relative
      rates of gene sequence divergence, and in this report we explore the connection
      between gene evolutionary rates and function. We performed a genome-scale
      evaluation of the relationship between evolutionary rates and functional
      annotations for the yeast Saccharomyces cerevisiae. Non-synonymous (dN) and
      synonymous (dS) substitution rates were calculated for 1,095 orthologous gene
      sets common to S. cerevisiae and six other closely related yeast species.
      Differences in evolutionary rates between pairs of genes (DeltadN & DeltadS) were
      then compared to their functional similarities (sGO), which were measured using
      Gene Ontology (GO) annotations. Substantial and statistically significant
      correlations were found between DeltadN and sGO, whereas there is no apparent
      relationship between DeltadS and sGO. These results are consistent with a mode of
      action for natural selection that is based on similar rates of elimination of
      deleterious protein coding sequence variants for functionally related genes. The
      connection between gene evolutionary rates and function was stronger than seen
      for phylogenetic profiles, which have previously been employed to inform
      functional inference. The co-evolution of functionally related yeast genes points
      to the relevance of specific function for the efficacy of natural selection and
      underscores the utility of gene evolutionary rates for functional predictions.

PMID- 18345353
TI  - Imaging hematopoietic precursor division in real time.
AB  - Stem cells are thought to balance self-renewal and differentiation through
      asymmetric and symmetric divisions, but whether such divisions occur during
      hematopoietic development remains unknown. Using a Notch reporter mouse, in which
      GFP acts as a sensor for differentiation, we image hematopoietic precursors and
      show that they undergo both symmetric and asymmetric divisions. In addition we
      show that the balance between these divisions is not hardwired but responsive to
      extrinsic and intrinsic cues. Precursors in a prodifferentiation environment
      preferentially divide asymmetrically, whereas those in a prorenewal environment
      primarily divide symmetrically. Oncoproteins can also influence division pattern:
      although BCR-ABL predominantly alters the rate of division and death, NUP98-HOXA9
      promotes symmetric division, suggesting that distinct oncogenes subvert different
      aspects of cellular function. These studies establish a system for tracking
      division of hematopoietic precursors and show that the balance of symmetric and
      asymmetric division can be influenced by the microenvironment and subverted by
      oncogenes.

PMID- 18345354
TI  - A diadenosine 5',5''-P1P4 tetraphosphate (Ap4A) hydrolase from Arabidopsis
      thaliana that is activated preferentially by Mn2+ ions.
AB  - Asymmetrical diadenosine 5',5''-P(1)P(4) tetraphosphate (Ap(4)A) hydrolases are
      key enzymes controlling the in vivo concentration of Ap(4)A--an important
      signaling molecule involved in regulation of DNA replication and repair,
      signaling in stress response and apoptosis. Sequence homologies indicate that the
      genome of the model plant Arabidopsis thaliana contains at least three open
      reading frames encoding presumptive Ap(4)A hydrolases: At1g30110, At3g10620, and
      At5g06340. In this work we present efficient overexpression and detailed
      biochemical characteristics of the AtNUDX25 protein encoded by the At1g30110
      gene. Aided by the determination of the binding constants of Mn(Ap(4)A) and
      Mg(Ap(4)A) complexes using isothermal titration calorimetry (ITC) we show that
      AtNUDX25 preferentially hydrolyzes Ap(4)A in the form of a Mn(2+) complex.

PMID- 18345355
TI  - The more things change...
AB  - After 5 years as Editor in Chief of Australian Family Physician, Associate
      Professor Steve Trumble is moving on to focus his attention on his career long
      interest in medical education as Associate Professor of Medical Education in the
      School of Medicine at the University of Melbourne.

PMID- 18345356
TI  - Urinary incontinence in the older patient.
AB  - Over a 7 year period from April 2000 to March 2007 urinary incontinence was
      managed 802 times for patients aged 45 years and over. Women made up 85% of these
      encounters. Women had a significantly higher rate of incontinence management than
      males in all age groups. However, the management rate for men rose significantly
      among those aged 75 years and over, compared with aged 45-74 years.

PMID- 18345357
TI  - Urinary incontinence-pathophysiology and management outline.
AB  - BACKGROUND: Urinary incontinence is common in the community and may impact
      significantly on quality of life; yet only one-third of sufferers seek medical
      attention. There are many treatment options for patients suffering with urinary
      incontinence. OBJECTIVE: This article aims to aid general practitioners in the
      management urinary incontinence. We outline the pathophysiology of urinary
      incontinence in women and provide a primary care treatment paradigm. Suggestions
      for when specialist referral would be of benefit are also discussed. DISCUSSION:
      Most urinary incontinence can be evaluated and treated in the primary care
      setting after careful history and simple clinical assessment. Initial treatment,
      for both urge urinary incontinence and stress urinary incontinence, is lifestyle
      modification and pelvic floor muscle treatment. Urinary urgency responds to
      bladder training and pharmacotherapy with anticholinergic medication.
      Pharmacotherapy has a limited place in stress incontinence. If there is complex
      symptomatology or primary management fails, then referral to a specialist is
      suggested.

PMID- 18345358
TI  - Urinary incontinence-assessment in women: stress, urge or both?
AB  - BACKGROUND: The aims of assessing urinary incontinence in women are to define the
      diagnosis, exclude other pathology and guide management. Treatment can be
      initiated when urinary incontinence is categorised as stress, urge or mixed
      incontinence. Once conservative measures have been exhausted, the management of
      stress incontinence is largely surgical, while that of urge urinary incontinence
      is largely medical. OBJECTIVE: This article discusses the clinical assessment of
      urinary incontinence in women with emphasis on the primary care assessment and
      indications for specialist referral. DISCUSSION: History taking is the
      cornerstone of urinary incontinence assessment and in combination with physical
      examination allows categorisation of patients into stress, urge or mixed urinary
      incontinence. Basic assessment includes investigations such as urine testing,
      bladder residual volume measurement, and a bladder diary. Urodynamic testing is
      not required in all patients or before initiating conservative treatment.
      Indications for specialist referral and urodynamic testing are discussed.

PMID- 18345359
TI  - Physiotherapy for urinary incontinence.
AB  - BACKGROUND: International guidelines recommend treatment for urinary incontinence
      by a health professional such as a pelvic floor or continence physiotherapist
      with specialised training in the management of pelvic floor disorders. OBJECTIVE:
      This article discusses the role of a physiotherapy program in treating women with
      urinary incontinence. DISCUSSION: Treatment usually involves five consultations
      with a pelvic floor physiotherapist over 4-6 months. After an assessment of
      bladder function and the pelvic floor muscles, an individualised training program
      is prescribed. The focus of pelvic floor muscle training is to build strength,
      endurance, speed and the coordination of the pelvic floor muscles in different
      situations. An effective program has been shown to increase contractile strength
      as well as increased resting tone of the pelvic floor, which then provides
      improved support of the pelvic organs higher in the pelvis. Women may be offered
      an annual review by their physiotherapist in order to promote long term
      continence.

PMID- 18345360
TI  - Urinary incontinence-procedural and surgical treatments for women.
AB  - BACKGROUND: A range of surgical treatment options is available for women
      suffering from stress and urge urinary incontinence refractory to conservative
      and medical management. OBJECTIVE: This article discusses the indications for
      surgical treatments for stress and urge urinary incontinence in women; and the
      advantages, disadvantages and side effects of these treatments. DISCUSSION: Women
      who fail to respond to pelvic floor physiotherapy for stress urinary incontinence
      have available to them a range of variably invasive surgical treatment options
      including bio-injectable agents, sling surgery, colposuspension, and prostheses.
      Women with urge urinary incontinence refractory to the newer anticholinergic
      agents can be treated with minimally invasive options such as bladder injections
      of botulinum toxin and sacral neuromodulation, as well as more invasive major
      urinary tract surgery.

PMID- 18345361
TI  - Treating the symptoms of osteoarthritis-oral treatments.
AB  - In 2004-2005, 15% of Australians reported having arthritis.1 Osteoarthritis (OA)
      is by far the most common form, and is a leading cause of pain and disability
      among people over 65 years of age.

PMID- 18345362
TI  - Beta blockers in systolic heart failure.
AB  - Heart failure is a common reason for general practice encounters. It affects 4%
      of Australians aged 45 years or over with the prevalence increasing from about 1%
      at age 50-59 years to more than 50% at 84 years of age and over. Patients with
      heart failure are increasingly managed in the primary care setting, and the
      emphasis of new national programs on early recognition of signs and diagnosis of
      heart failure suggest that this trend will continue. Beta blockers have been
      shown to reduce morbidity and mortality in patients with heart failure when used
      with an angiotensin converting enzyme inhibitor (ACEI) and a diuretic.

PMID- 18345363
TI  - More than just dry skin.
AB  - Harriet is worried about her husband George. You don't see George very often but
      he certainly looks different. Apart from the changes described by Harriet, George
      has put on a lot of weight (from 97 to 112 kg since his last 'weigh in' 14 months
      ago). George is in his early 40s and in the past has been an active, quickly
      moving man despite his size (height 194 cm). Now he seems listless and lethargic.

PMID- 18345364
TI  - Lessons from the TAPS study-knowledge and skills errors.
AB  - The Threats to Australian Patient Safety (TAPS) Study collected 648 anonymous
      reports about threats to patient safety from a representative random sample of
      Australian general practitioners. These contained any events the GPs felt should
      not have happened and would not want to happen again, regardless of who was at
      fault or the outcome of the event. This series of articles presents clinical
      lessons resulting from the TAPS study.

PMID- 18345365
TI  - A man with contracted fingers.
AB  - An Indian man from Malaysia presented with contracture of his hands. He is 55
      years of age and has a history of chronic alcohol consumption. Examination
      revealed bilateral thickened structure at the palms.

PMID- 18345366
TI  - End of life decisions and the law.
AB  - On 17 October 2004, Mr Isaac Messiha, 75 years of age, was admitted to the
      intensive care unit (ICU) following an out of hospital cardiac arrest. It was
      estimated that 25 minutes had elapsed before the arrival of ambulance officers
      and the commencement of cardiopulmonary resuscitation (CPR).

PMID- 18345367
TI  - A mirror or a window? The Irish Registrar Exchange Program.
AB  - In mid 2007 I had the opportunity to take part in a registrar exchange program
      established between my current Regional Training Provider (getGP) and the Donegal
      Specialist Training Program in General Practice in Ireland. It seemed too good a
      chance to pass up; a 3 month work placement in a small town with accommodation
      and a car provided, and without much of the tedious paperwork that working
      overseas often seems to bestow. There was that, and the promise of rolling green
      fields, the famed Irish hospitality and a smacking good pint of Guinness.

PMID- 18345368
TI  - Improving chronic illness care-revisiting the role of care planning.
AB  - BACKGROUND: Chronic illness is increasingly being recognised as a widespread,
      debilitating and costly burden. Most models of care used in the acute care
      setting are inappropriate for chronic illness and are costly. OBJECTIVE: This
      article examines the goals of chronic illness care in the Australian general
      practice context and related issues from a conceptual perspective. It describes
      developments in care planning in Australia, particularly Medicare payments for
      care planning, and discusses how such developments can assist general
      practitioners in patient care. A case study of an Aboriginal patient with chronic
      illness is described to illustrate the issues discussed. DISCUSSION: Care
      planning/management based on a partnership model can bring about some success in
      management, even with the most difficult cases. Illness support, management of
      rest of life conditions and treatment and self management of disease are
      required. Care planning/management items, as part of the Enhanced Primary Care
      program provide incentive payments to address key models of improving complex
      chronic care. This can result in improved system organisation and self management
      of chronic illness.

PMID- 18345369
TI  - A pilot study of telephone based asthma management.
AB  - BACKGROUND: Self management programs have been advocated for adults who have
      recently been admitted to hospital or have recently attended an emergency
      department because of asthma. A new telephone based approach has already been
      trialled for the management of a number of other chronic conditions. This study
      sought to determine the effect of a telephone based asthma management program for
      adults with asthma. METHODS: Adults with one or more previous admissions for
      asthma to either or both of two tertiary hospitals between 1 May 2001 and 30
      November 2003 were invited to participate. All participants received one face-to
      face session with an asthma educator. Participants were randomised to
      intervention (six telephone calls over 6 months) or control (usual care) groups.
      Measures of health care utilisation and morbidity were collected weekly for 12
      months. RESULTS: Seventy-one adults (54 females) with a mean age of 36.2 years
      were recruited to the study. Twenty hospital re-admissions were recorded for the
      control group and one for the intervention group at 12 months. Re-admission was
      significantly associated with allocation to control group (p=0.05). The control
      group was significantly more likely to report being woken by asthma on more than
      half the nights of the week (p=0.03). DISCUSSION: Telephone based self management
      intervention results in clinically important reductions in hospital re-admission
      in adults previously hospitalised with asthma.

PMID- 18345370
TI  - Getting the message across-professional interpreters in general practice.
AB  - BACKGROUND: Evidence and quality standards support the use of professional
      interpreters and discourage the use of family interpreters in medical
      consultations. The Northern Division of General Practice documented the use of
      professional and family interpreters in local general practices, together with
      barriers and possible facilitators in the use of professional interpreters.
      METHODS: Two complementary surveys were conducted in September 2006: practices
      were surveyed through a brief phone interview; and a written questionnaire with
      multiple choice and Likert scale questions was distributed to general
      practitioners attending division training sessions during the same period.
      DISCUSSION: Surveys of practices and GPs found the use of professional
      interpreters is uncommon. Over two-thirds of practices reported never using the
      free Doctors Priority Line phone interpreting service. Family members were
      frequently used as interpreters, with most GPs preferring to use family rather
      than professional interpreters. Over a third of practices were unaware of the
      Doctors Priority Line. Findings suggested that relevant standards are commonly
      not understood or implemented.

PMID- 18345371
TI  - Breast and cervical cancer in indigenous women-overcoming barriers to early
      detection.
AB  - BACKGROUND: Aboriginal and Torres Strait Islander women have a higher incidence
      of cervical cancer and poorer outcomes for breast and cervical cancer than
      nonindigenous women. This article reports on a project that aimed to implement
      and evaluate strategies to improve general practitioner early detection of breast
      and cervical cancer in this group. METHODS: In three sites a female indigenous
      worker and female GP developed and implemented local plans aimed to improve
      service coordination and access, GP knowledge, recall systems, and health
      promotion. Evaluation included analysis of qualitative and quantitative data from
      project reports and surveys. RESULTS: Project officers and partners identified
      collaboration between service providers, community participation in planning and
      delivery, an indigenous health worker raising awareness in both the women and
      GPs, and a female GP providing a holistic service as important factors in project
      success. Increased cervical screening was documented in one site and a trend
      toward increased breast and cervical screening in another. DISCUSSION:
      Partnerships involving community members planning and implementing evidence based
      strategies may improve participation of Aboriginal and Torres Strait Islander
      women in breast and cervical cancer screening.

PMID- 18345372
TI  - Promoting e-communication-lessons from a feasibility study.
AB  - There has been a rapid uptake in the use of computers in general practice during
      the past decade. General practitioners initially used computers primarily to
      generate prescriptions, but have increasingly adopted computers for health record
      keeping. While most practices are now receiving pathology and radiology results
      via the internet, electronic communication (e-communication) between GPs and
      other health care providers remains limited. Making referrals, communicating to
      and from medical specialists and allied health practitioners, and obtaining
      important health information from hospitals and other health care organisations
      have all proven difficult to implement in electronic form.

PMID- 18345373
TI  - Concepts of sexuality and health among Iranian women in Australia.
AB  - BACKGROUND: Like other immigrants, Iranians face difficulties using sexual and
      reproductive health services in Australia. Expectations may be affected by
      experiences of population control services in Iran. METHODS: Fifty-one Iranian
      women in Sydney (New South Wales) participated in individual interviews and focus
      groups in 2003-2004. Recorded interviews were transcribed and translated into
      English and subjected to thematic and narrative analysis. RESULTS: Concepts of
      sexual health among respondents centred on reproductive gynaecology: pregnancy,
      contraception and menopause. Issues around relationships or sexual pleasure or
      pain were not thought of as being issues of 'sexual health'. DISCUSSION:
      Communication with sexual health caregivers is hampered by the euphemistic, vague
      and symbolically loaded terminology used by the women in their own language, and
      their lack of knowledge of English and medical terms. They are reluctant to use
      interpreters and lack faith in their right to confidentiality. Practical
      suggestions for providing appropriate clinical care include the use of
      communication aids, approaching the topic obliquely and interviewing the woman's
      husband where appropriate.

PMID- 18345378
TI  - The role of MHC haplotypes H2d/H2b in mouse resistance/susceptibility to cyst
      formation is influenced by the lineage of infective Toxoplasma gondii strain.
AB  - Toxoplasma gondii strains displaying the Type I/III genotype are associated with
      acquired ocular toxoplasmosis in humans. Here, we used a mice model to
      characterize some immunological mechanisms involved in host resistance to
      infection with such strains. We have chosen the Type I/III strains D8, G2 and P
      Br, which cause a chronic infection in mice that resembles human toxoplamosis.
      Mice deficient of molecules MyD88, IFN-gamma, and IL-12 were susceptible to all
      three parasite strains. This finding indicates the importance of innate
      mechanisms in controlling infection. On the other hand, MHC haplotype did not
      influenced resistance/susceptibility; since mice lineages displaying a same
      genetic background but different MHC haplotypes (H2b or H2d) developed similar
      mortality and cyst numbers after infection with those strains. In contrast, the
      C57BL/6 genetic background, and not MHC haplotype, was critical for development
      of intestinal inflammation caused by any of the studied strains. Finally,
      regarding effector mechanisms, we observed that B and CD8+ T lymphocytes
      controlled survival,whereas the inducible nitric oxide synthase influenced cyst
      numbers in brains of mice infected with Type I/III strains. These findings are
      relevant to further understanding of the immunologic mechanisms involved in host
      protection and pathogenesis during infection with T. gondii.

PMID- 18345379
TI  - Amazon Forest maintenance as a source of environmental services.
AB  - Amazonian forest produces environmental services such as maintenance of
      biodiversity, water cycling and carbon stocks. These services have a much greater
      value to human society than do the timber, beef and other products that are
      obtained by destroying the forest. Yet institutional mechanisms are still lacking
      to transform the value of the standing forest into the foundation of an economy
      based on maintaining rather than destroying this ecosystem. Forest management for
      commodities such as timber and non-timber forest products faces severe
      limitations and inherent contradictions unless income is supplemented based on
      environmental services. Amazon forest is threatened by deforestation, logging,
      forest fires and climate change. Measures to avoid deforestation include
      repression through command and control, creation of protected areas, and
      reformulation of infrastructure decisions and development policies. An economy
      primarily based on the value of environmental services is essential for long-term
      maintenance of the forest. Much progress has been made in the decades since I
      first proposed such a transition, but many issues also remain unresolved. These
      include theoretical issues regarding accounting procedures, improved
      quantification of the services and of the benefits of different policy options,
      and effective uses of the funds generated in ways that maintain both the forest
      and the human population.

PMID- 18345380
TI  - The evidence for hippocampal long-term potentiation as a basis of memory for
      simple tasks.
AB  - Long-term potentiation (LTP) is the enhancement of postsynaptic responses for
      hours, days or weeks following the brief repetitive afferent stimulation of
      presynaptic afferents. It has been proposed many times over the last 30 years to
      be the basis of long-term memory. Several recent findings finally supported this
      hypothesis: a) memory formation of one-trial avoidance learning depends on a
      series of molecular steps in the CA1 region of the hippocampus almost identical
      to those of LTP in the same region; b)hippocampal LTP in this region accompanies
      memory formation of that task and of another similar task. However, CA1 LTP and
      the accompanying memory processes can be dissociated, and in addition plastic
      events in several other brain regions(amygdala, entorhinal cortex, parietal
      cortex) are also necessary for memory formation of the one-trial task, and
      perhaps of many others.

PMID- 18345381
TI  - Inhibition of caspase-8 activity reduces IFN-gamma expression by T cells from
      Leishmania major infection.
AB  - Following infection with Leishmania major, T cell activation and apoptosis can be
      detected in draining lymph nodes of C57BL/6-infected mice. We investigated the
      mechanisms involved in apoptosis and cytokine expression following T cell
      activation. After two weeks of infection, apoptotic T cells were not detected in
      draining lymph nodes but activation with anti-CD3 induced apoptosis in both CD4
      and CD8 T cells. Treatment with anti-Fas Ligand, caspase-8 or caspase- 9
      inhibitors did not block activation-induced T-cell death. We also investigated
      whether the blockade of caspase-8 activity would affect the expression of type-1
      or type-2 cytokines. At early stages of infection, both CD4 and CD8 T cells
      expressed IFN-gamma upon activation. Treatment with the caspase-8 inhibitor zIETD
      fmk (benzyl-oxycarbonyl-Ile- Glu(OMe)-Thr-Asp(OMe)-fluoromethyl ketone) reduced
      the proportion of CD8 T cells and IFN-gamma expression in both CD4 and CD8 T
      cells. We conclude that a non apoptotic role of caspase-8 activity may be
      required for T cell-mediated type-1 responses during L. major infection.

PMID- 18345382
TI  - High susceptibility of activated lymphocytes to oxidative stress-induced cell
      death.
AB  - The present study provides evidence that activated spleen lymphocytes from Walker
      256 tumor bearing rats are more susceptible than controls to tert-butyl
      hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator
      and antioxidant deferoxamine, the intracellular Ca2+ chelator BAPTA, the L-type
      Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition
      inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control
      and activated lymphocytes equally resistant to the toxic effects of t-BOOH.
      Incubation of activated lymphocytes in the presence of t-BOOH resulted in a
      cyclosporin A-sensitive decrease in mitochondrial membrane potential. These
      results indicate that the higher cytosolic Ca2+ level in activated lymphocytes
      increases their susceptibility to oxidative stress-induced cell death in a
      mechanism involving the participation of mitochondrial permeability transition.

PMID- 18345383
TI  - Correlation between voxel based morphometry and manual volumetry in magnetic
      resonance images of the human brain.
AB  - This is a comparative study between manual volumetry (MV) and voxel based
      morphometry (VBM) as methods of evaluating the volume of brain structures in
      magnetic resonance images. The volumes of the hippocampus and the amygdala of 16
      panic disorder patients and 16 healthy controls measured through MV were
      correlated with the volumes of gray matter estimated by optimized modulated VBM.
      The chosen structures are composed almost exclusively of gray matter. Using a 4
      mm Gaussian filter, statistically significant clusters were found bilaterally in
      the hippocampus and in the right amygdala in the statistical parametric map
      correlating with the respective manual volume. With the conventional 12 mm
      filter,a significant correlation was found only for the right hippocampus.
      Therefore, narrow filters increase the sensitivity of the correlation procedure,
      especially when small brain structures are analyzed. The two techniques seem to
      consistently measure structural volume.

PMID- 18345384
TI  - Active transcription and ultrastructural changes during Trypanosoma cruzi
      metacyclogenesis.
AB  - The differentiation of proliferating epimastigote forms of Trypanosoma cruzi ,
      the protozoan parasite that causes Chagas disease, into the infective and non
      proliferating metacyclic forms can be reproduced in the laboratory by incubating
      the cells in a chemically-defined medium that mimics the urine of the insect
      vector. Epimastigotes have a spherical nucleus, a flagellum protruding from the
      middle of the protozoan cell, and a disk-shaped kinetoplast -- an organelle that
      corresponds to the mitochondrial DNA. Metacyclic trypomastigotes have an
      elongated shape with the flagellum protruding from the posterior portion of the
      cell and associated with a spherical kinetoplast. Here we describe the
      morphological events of this transformation and characterize a novel intermediate
      stage by three-dimensional reconstruction of electron microscope serial sections.
      This new intermediate stage is characterized by a kinetoplast compressing an
      already elongated nucleus, indicating that metacyclogenesis involves active
      movements of the flagellar structure relative to the cell body. As transcription
      occurs more intensely in proliferating epimastigotes than in metacyclics, we also
      examined the presence of RNA polymerase II and measured transcriptional activity
      during the differentiation process. Both the presence of the enzyme and
      transcriptional activity remain unchanged during all steps of metacyclogenesis.
      RNA polymerase II levels and transcriptional activity only decrease after
      metacyclics are formed. We suggest that transcription is required during the
      epimastigote-to-metacyclic trypomastigote differentiation process, until the
      kinetoplast and flagellum reach the posterior position of the parasites in the
      infective form.

PMID- 18345385
TI  - COL18A1 is highly expressed during human adipocyte differentiation and the SNP
      c.1136C > T in its "frizzled" motif is associated with obesity in diabetes type 2
      patients.
AB  - Collagen XVIII can generate two fragments, NC11-728 containing a frizzled motif
      which possibly acts in Wnt signaling and Endostatin, which is cleaved from the
      NC1 and is a potent inhibitor of angiogenesis. Collagen XVIII and Wnt signaling
      have recently been associated with adipogenic differentiation and obesity in some
      animal models, but not in humans. In the present report, we have shown that
      COL18A1 expression increases during human adipogenic differentiation. We also
      tested if polymorphisms in the Frizzled (c.1136C>T; Thr379Met) and Endostatin
      (c.4349G>A; Asp1437Asn) regions contribute towards susceptibility to obesity in
      patients with type 2 diabetes (113 obese, BMI > or =30; 232 non-obese, BMI < 30)
      of European ancestry. No evidence of association was observed between the allele
      c.4349G>A and obesity, but we observed a significantly higher frequency of
      homozygotes c.1136TT in obese (19.5%) than in non-obese individuals (10.9%) [P =
      0.02; OR = 2.0 (95%CI: 1.07-3.73)], suggesting that the allele c.1136T is
      associated to obesity in a recessive model. This genotype, after controlling for
      cholesterol, LDL cholesterol, and triglycerides, was independently associated
      with obesity (P = 0.048), and increases the chance of obesity in 2.8 times.
      Therefore, our data suggest the involvement of collagen XVIII in human
      adipogenesis and susceptibility to obesity.

PMID- 18345386
TI  - Cyclic nitroxides inhibit the toxicity of nitric oxide-derived oxidants:
      mechanisms and implications.
AB  - The substantial therapeutic potential of tempol (4-hydroxy-2,2,6,6-tetramethyl-1
      piperidinyloxy) and related cyclic nitroxides as antioxidants has stimulated
      innumerous studies of their reactions with reactive oxygen species. In
      comparison, reactions of nitroxides with nitric oxide-derived oxidants have been
      less frequently investigated. Nevertheless, this is relevant because tempol has
      also been shown to protect animals from injuries associated with inflammatory
      conditions, which are characterized by the increased production of nitric oxide
      and its derived oxidants. Here, we review recent studies addressing the
      mechanisms by which cyclic nitroxides attenuate the toxicity of nitric oxide
      derived oxidants. As an example, we present data showing that tempol protects
      mice from acetaminophen-induced hepatotoxicity and discuss the possible
      protection mechanism. In view of the summarized studies, it is proposed that
      nitroxides attenuate tissue injury under inflammatory conditions mainly because
      of their ability to react rapidly with nitrogen dioxide and carbonate radical. In
      the process the nitroxides are oxidized to the corresponding oxammonium cation,
      which, in turn, can be recycled back to the nitroxides by reacting with upstream
      species, such as peroxynitrite and hydrogen peroxide, or with cellular
      reductants. An auxiliary protection mechanism may be down-regulation of inducible
      nitric oxide synthase expression. The possible therapeutic implications of these
      mechanisms are addressed.

PMID- 18345387
TI  - Vegetation and hydrology changes in Eastern Amazonia inferred from a pollen
      record.
AB  - Pollen, charcoal, and C14 analyses were performed on a sediment core obtained
      from Lake Tapera (Amapa) to provide the palaeoenvironmental history of this part
      of Amazonia. A multivariate analysis technique, Detrended Correspondence
      Analysis, was applied to the pollen data to improve visualization of sample
      distribution and similarity. A sedimentary hiatus lasting 5,500 years was
      identified in the Lake Tapera. Because the timing of the hiatus overlapped with
      the highest Holocene sea-level, which would have increased the local water table
      preventing the lake from drying out, it is clear that sea-level was not important
      in maintaining the lake level. Lake Tapera probably depended on riverine flood
      waters, and the sedimentary gap was caused by reduced Amazon River discharge, due
      to an extremely dry period in the Andes (8,000-5,000 years BP), when
      precipitation levels markedly decreased. The lack of Andean pollen (river
      transported) in the record after this event supports this interpretation. The
      pollen analysis shows that when sedimentation resumed in 1,620 cal. years BP, the
      vegetation around the lake was changed from forest into savanna. This record
      demonstrates the need to improve our understanding of climate changes and their
      associated impacts on vegetation dynamics.

PMID- 18345388
TI  - Deficit of sand in a sediment transport model favors coral reef development in
      Brazil.
AB  - This paper shows that the location of the shoreface bank reefs along the
      northeastern and eastern coasts of Brazil, in a first order approximation, seem
      to be controlled by the deficit of sediment in the coastal system. The sediment
      transport pattern defined by a numerical modeling of wave refraction diagrams,
      representing circa 2000 km of the northeastern and eastern coasts of Brazil,
      permitted the regional-scale reproduction of several drift cells of net longshore
      sediment transport. Those drift cells can reasonably explain the coastal sections
      that present sediment surplus or sediment deficit, which correspond,
      respectively, to regions where there is deposition and erosion or little/no
      deposition of sand. The sediment deficit allows the exposure and maintenance of
      rocky substrates to be free of sediment, a favorable condition for the fixation
      and development of coral larvae.

PMID- 18345389
TI  - [Online submission of the journal ABE&M: an expected victory].

PMID- 18345390
TI  - [One hundred years of Japanese immigration in Brazil: socio-metabolic lessons].

PMID- 18345391
TI  - [Sympathetic system hyperactivity in obesity].

PMID- 18345392
TI  - [Kallmann syndrome: a historical [corrected] clinical and molecular review].
AB  - Kallmann syndrome (KS), the association of hypogonadotropic hypogonadism and
      anosmia, was described by Maestre de San Juan in 1856 and characterized as a
      hereditary condition by Franz Josef Kallmann in 1944. Many aspects such as
      pathogeny, phenotype and genotype in KS were described in the last fifteen years.
      The knowledge of this condition has grown fast, making it difficult to update.
      Here we review historical aspects of this condition and its discoverers and
      describe new findings regarding the embryogenesis of the olfactory bulb and GnRH
      secreting neuronal tracts that are important for understanding the association of
      hypogonadism and anosmia. Additionally, we describe the phenotypic and genotypic
      heterogeneity of KS, including five related genes (KAL-1, FGFR1, PROKR2, PROK2 e
      NELF), and discuss the function of each codified protein in migration and
      maturation of the olfactory and GnRH neurons, with data from in vitro and in vivo
      studies. Finally we describe the clinical phenotype of patients carrying these
      mutations.

PMID- 18345393
TI  - Update on the etiology, diagnosis and therapeutic management of sexual precocity.
AB  - Precocious puberty is defined as the development of secondary sexual
      characteristics before the age of 8 years in girls and 9 years in boys.
      Gonadotropin-dependent precocious puberty (GDPP) results from the premature
      activation of the hypothalamic-pituitary-gonadal axis and mimics the
      physiological pubertal development, although at an inadequate chronological age.
      Hormonal evaluation, mainly through basal and GnRH-stimulated LH levels shows
      activation of the gonadotropic axis. Gonadotropin-independent precocious puberty
      (GIPP) is the result of the secretion of sex steroids, independently from the
      activation of the gonadotropic axis. Several genetic causes, including
      constitutive activating mutations in the human LH-receptor gene and activating
      mutations in the Gs protein a-subunit gene are described as the etiology of
      testotoxicosis and McCune-Albright syndrome, respectively. The differential
      diagnosis between GDPP and GIPP has direct implications on the therapeutic
      option. Long-acting gonadotropin-releasing hormone (GnRH) analogs are the
      treatment of choice in GDPP. The treatment monitoring is carried out by clinical
      examination, hormonal evaluation measurements and image studies. For treatment of
      GIPP, drugs that act by blocking the action of sex steroids on their specific
      receptors (cyproterone, tamoxifen) or through their synthesis (ketoconazole,
      medroxyprogesterone, aromatase inhibitors) are used. In addition, variants of the
      normal pubertal development include isolated forms of precocious thelarche,
      precocious pubarche and precocious menarche. Here, we provide an update on the
      etiology, diagnosis and management of sexual precocity.

PMID- 18345394
TI  - [Critical analysis on the use of the homeostasis model assessment (HOMA) indexes
      in the evaluation of the insulin resistance and the pancreatic beta cells
      functional capacity].
AB  - Beta-cell dysfunction and insulin resistance are interrelated metabolic
      abnormalities in the aetiology of Type 2 Diabetes. In several countries,
      increases in the prevalence of obesity and diabetes have been observed in
      association with the presence of insulin resistance. In this context, measurement
      of insulin resistance and beta-cell function is useful. The HOMA indexes
      (Homeostasis Model Assessment) have been widely used, representing an alternative
      for the evaluation of these parameters, particularly as a fast, easy and cheap
      method. This review discusses the origin and evolution of the HOMA index, as well
      as details of the method, analyzing features related to its validation and the
      cutoff limits for its interpretation.

PMID- 18345395
TI  - [Lipid profile disturbances are highly prevalent in Japanese-Brazilians].
AB  - High prevalence of diabetes has been previously reported in Japanese-Brazilians.
      In an attempt to better estimate the cardiometabolic risk, this study evaluated
      lipid disorders in 1,330 Japanese-Brazilians (46% men) aged>30 years.
      Hypercholesterolemia was defined as serum cholesterol>240 mg/dL,
      hypertriglyceridemia as values>150 mg/dL and low-HDL-C as values<40 mg/dL and <50
      mg/dl for men and women respectively. The prevalence of dyslipidemias was
      compared by the chi-square test between gender and glycemic category. Mean and
      Standard Deviation of lipids and lipoproteins were compared by the Student t-Test
      between gender. Hypertriglyceridemia was detected in 66.0% [95% CI: 63.5-68.5] of
      the population, being more common in men and increasing with deterioration of
      glucose metabolism. Mean level of triglycerides was 235.7+/-196.3 mg/dL. The
      prevalence of hypercholesterolemia was 24.4% [95% CI: 22.1-26.7]. Low HDL-C was
      observed in 17.5% [95% CI: 14.5-20.5] of men and 43.0% [95% CI: 39.4- 46.6] of
      women but total/HDL-cholesterol ratio was lower in women (4.23+/-0.68 vs. 4.40+/
      0.73, p<0.001). In Japanese-Brazilians, hypertriglyceridemia is the commonest
      dyslipidemia, in agreement with the high prevalence of diabetes. Men showed a
      worse lipid profile than women; it was suggested that the Western diet and living
      habits could be deteriorating their health.

PMID- 18345396
TI  - [Effects of neuroendocrine obesity induction on systemic hemodynamics and left
      ventricular function of normotensive rats].
AB  - The aim of this study was to evaluate the effects of obesity induced by neonatal
      Monosodium Glutamate (MSG) administration upon body weight, tail blood pressure,
      systemic hemodynamics and left ventricular function of Wistar rats. Two groups of
      Wistar rats were prepared: a) 18 animals made obese through the administration of
      2 mg/Kg/SC of MSG during the first 11 days of the neonatal period and b)16
      control animals (vehicle treated for the same period). Adults animals were
      followed from the 3rd up the 6th month of life with blood pressure and body
      weight being measured twice a week. At the end of this period, in part of animals
      from both groups, we evaluated the left ventricular function through the
      Langendorff isolated heart preparation whereas the remainders were used to
      evaluate the systemic hemodynamics through a termodilution method. RESULTS: MSG
      animals showed significant increases in heart rate (WST=235.0+/-35.1; MSG=312.0+/
      90.8 bpm), total peripheral resistance (WST=0.312+/-0.100; MSG=0.535+/-0.195
      mmHg.ml(-1).min) and in relative epididymal adipose tissue content (WST=2.076+/
      0.622; MSG=2.731+/-0.722 g/100 g) and a reduction of systolic volume (WST=1.020+/
      0.364; MSG=0.748+/-0.455 microl/bat). An increase in mean arterial pressure was
      also detected in obese animals during the hemodynamic evaluation. The increases
      in HR and TPR and the reduction in SV suggest an augmentation in the sympathetic
      activation of those obese normotensive rats associated with an increased visceral
      fat deposition.

PMID- 18345397
TI  - [Evaluation of glucose metabolism in acromegalic patients before and after
      treatment with octreotide LAR].
AB  - AIM OF THE STUDY: To evaluate the glucose metabolism in acromegalic patients
      before and after treatment with octreotide LAR. PATIENTS AND METHODS: This was a
      prospective and longitudinal study involving 30 patients from the acromegaly
      research outpatient clinic of the Endocrinology unit of the HUCFF/UFRJ. They
      underwent clinical and laboratorial evaluations, with measurements of growth
      hormone (GH), insulin-like growth factor type I (IGF-I), insulin, proinsulin, C
      peptide, glycosylated hemoglobin (HbA1c), IGF binding protein type 1 (IGFBP-1)
      and glucose, during oral glucose tolerance test (OGTT), before and after six
      months of treatment with octreotide LAR. The Wilcoxon signed-rank test was used
      and values of 5% were considered statistically significant. RESULTS: We found 16
      (54%) patients with normal glucose tolerance, 7 (23%) with impaired glucose
      tolerance and 7 (23%) diabetics. Twelve patients completed the six-month
      treatment, out of which three showed worsening of glucose tolerance and two
      (diabetics) had worse blood glucose control. Whereas there was an increase in
      waist circumference (p=0.03), there was a decrease in GH (p=0.04), with %IGF-I
      above the upper limit of reference values (% ULRV) [p=0.001], insulin (p=0.019),
      C peptide levels (p=0.002) and homeostatic model assessment (HOMA-IR) [p=0.039].
      CONCLUSIONS: In this series, treatment with octreotide LAR led to a worsening of
      glucose tolerance in three non-diabetic patients and worsened glycemic control in
      two diabetics, in spite of reducing insulin resistance.

PMID- 18345398
TI  - Blood pressure and cardiorenal responses to antihypertensive therapy in obese
      women.
AB  - OBJECTIVE: Blood pressure (BP) and target organ responses to antihypertensive
      drugs are not well established in hypertensive obese patients. This study is
      aimed at evaluating the effects of obesity and adiposity distribution patterns on
      these responses. METHODS: 49 hypertensive obese women were designated to
      different groups according to waist to hip ratio measurements--37 with troncular
      and 12 with peripheral obesity. Patients were treated for 24-weeks on a stepwise
      regimen with cilazapril alone or a cilazapril/hydrochlorothiazide/amlodipine
      combination therapy to achieve a BP lower than 140/90 mmHg. Ambulatory blood
      pressure monitoring (ABPM), echocardiography, and albuminuria were assessed
      before and after the intervention. RESULTS: After 24 weeks, weight loss was less
      than 2% in both groups. ABPM targets were achieved in 81.5% of patients upon a
      combination of 2(26.5%) or 3(55.1%) drugs. Similar reductions in daytime-SBP/DBP:
      -22.5/-14.1(troncular obesity)/-23.6/-14.9 mmHg (peripheral obesity) were
      obtained. Decrease in nocturnal-SBP was greater in troncular obesity patients.
      Upon BP control, microalbuminuria was markedly decreased, while only slight
      decrease in left ventricular mass was observed for both groups. CONCLUSIONS: In
      the absence of weight loss, most patients required combined antihypertensive
      therapy to control their BP, regardless of their body fat distribution pattern.
      Optimal target BP and normal albuminuria were achieved in the group as a whole
      and in both obese patient groups, while benefits to cardiac structure were of a
      smaller magnitude.

PMID- 18345399
TI  - [Analysis of resting metabolic rate evaluated by indirect calorimetry in obese
      women with low and high caloric intake].
AB  - The aim of this study was to evaluate if obese women with the lowest values of
      caloric intake (CI) determined by food questionnaire also present the lowest
      values of resting metabolic rate (RMR), which could lead to excessive weight
      gain, caused by changes in energy balance. With this purpose, 77 obese women,
      with IMC>30 kg/m2, aged 20 to 45 years, had their physical activity level and CI
      evaluated. According to the values of CI obtained from food intake reports, the
      participants were divided in 3 groups: low (G1), medium (G2), high (G3) CI and
      were submitted to indirect calorimetry. Height, weight, body surface area (BSA),
      fat free mass and fat mass measured by bioimpedance were evaluated. The highest
      values of weight, BSA an fat mass were obtained in G1, as well as values above
      1.2 for the CI:RMR ratio, which indicates a probable underestimation of CI. The
      highest values of physical activity and RMR were observed in the G3 (with high
      caloric intake). In conclusion, this paper shows that a tendency towards
      underestimation of self-reported caloric intake exists among obese women and that
      the maintenance of weight in some patients can be due to their low level of
      physical activity.

PMID- 18345400
TI  - [Overweight in adolescent offspring of women with hyperglycemia during
      pregnancy].
AB  - AIM: To verify whether different hyperglycemia levels during pregnancy cause
      frequency differences in adolescent obesity and its morbidities in the offspring.
      METHODS: Seventy-three children were divided into three groups according to
      maternal glucose tolerance: G1 (n=27) normal oral glucose tolerance test (OGTT)
      and daily glycemia (DG); G2 (n=23) normal OGTT and high DG; G3 (n=23) abnormal
      OGTT and DG (gestational diabetes mellitus; GDM). All underwent clinical
      evaluation (anthropometry) a questionnaire(neonatal data, eating habits), and
      determination of fasting serum glucose and lipid profile measurement. Analysis of
      variance (ANOVA) and the Goodmans test were used to compare the groups. RESULTS:
      G3 mothers showed higher fasting plasma glucose(FPG) and DG than G2 and G1(FPG:
      93+/-10 vs 83+/-5 vs 78+/-10 mg/dL; DG: 104+/-12 vs 93+/-7 vs 85+/-9 mg/dL,
      respectively; P<0.001). G2 mothers had higher DG than G1 (93+/-7 vs 85+/-9 mg/dL;
      P<0.001). G3 offspring birthweight was higher than G1 and G2 (3,667+/-527 vs
      3,167+/-565 and 3,282+/-401 g, respectively; P<0.05). More G3 offspring were
      overweight than G1 (52.2 vs 14.8%; P<0.05). CONCLUSIONS: Offspring of GDM mothers
      with fasting and daily hyperglycemia have higher birthweight and overweight
      frequency in adolescence. These children must be followed up from infancy.

PMID- 18345401
TI  - Premature thelarche: clinical and laboratorial assessment by
      immunochemiluminescent assay.
AB  - In order to establish cut-off limits and to distinguish isolated premature
      thelarche (IPT) from precocious puberty (PP), we evaluated data from 79 girls
      with premature thelarche, comparing basal and stimulated LH and FSH serum
      concentrations with those from 91 healthy girls. A GnRH stimulation test was
      performed in 10 normal girls and in 42 with premature thelarche. Comparison among
      groups was performed by Kruskal-Wallis and Dunns tests. LH values were
      significantly greater in girls with IPT than in control groups. Basal
      gonadotropin concentrations were higher in patients with PP than in controls, but
      not different from patients with IPT. Peak LH levels after GnRH stimulation
      distinguished those two groups, with a cut-off value of 4.0 IU/L, but still with
      minimal overlap. In conclusion, a girl with premature thelarche and LH peak value
      above 4.5 IU/L has, indeed, PP, but values between 3.5 and 4.5 IU/L point to
      careful follow-up.

PMID- 18345402
TI  - [Comparative study of prednisolone versus hydrocortisone acetate for treatment of
      patients with the classic congenital adrenal hyperplasia due to 21-hydroxylase
      deficiency].
AB  - Hydrocortisone acetate is usually employed in the treatment of classic congenital
      adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. In Brazil, however,
      oral hydrocortisone acetate is only available from manipulation pharmacies.
      Prednisolone has stable oral pharmaceutical formulations commercially available,
      with the advantage of a single daily dose. The aim of this study was to compare
      the efficacy of oral prednisolone and oral hydrocortisone in the treatment of CAH
      due to 21-hydroxylase deficiency. Fifteen patients with mean (SD) chronological
      age of 7.2 (3.6) years, were evaluated in two consecutive 1-year periods. In the
      first year, hydrocortisone (17.5 mg/m2/day, divided in three doses) was used in
      the treatment, followed by the use of prednisolone (3 mg/m2/day, once in the
      morning) in the second year. The comparison between the two treatments was
      assessed after a one-year treatment period by: variation of height standard
      deviation score (SDS) (delta Height SDS), variation of height SDS according to
      bone age (delta BA SDS), variation of body mass SDS (delta BMI SDS) and serum
      levels of androstenedione. No significant difference was observed in relation to
      the delta Height SDS, delta BA SDS and delta BMI SDS. No significant difference
      was observed in the serum levels of androstenedione. We conclude that the
      efficacy of prednisolone administered once a day orally is comparable to the oral
      use of hydrocortisone three times a day. Oral prednisolone may be an option for
      patients with CAH due to 21-hydroxylase deficiency.

PMID- 18345403
TI  - Triiodothyronine (T3) does not induce Rankl expression in rat Ros 17/2.8 cells.
AB  - Osteoclastogenesis may be regulated via activation of the RANK/RANKL (receptor
      activator of nuclear factor-kappa B/receptor activator of nuclear factor-kappa B
      ligand) system, which is mediated by osteoblasts. However, the bone loss
      mechanism induced by T3 (triiodothyronine) is still controversial. In this study,
      osteoblastic lineage rat cells (ROS 17/2.8) were treated with T3 (10(-8) M, 10(
      9) M, and 10(-10) M), and RANKL mRNA (messenger RNA) expression was measured by
      semiquantitative RT-PCR. Our results show that T3 concentrations used did not
      significantly enhance RANKL expression compared to controls without hormone
      treatment. This data suggests that other mechanisms, unrelated to the RANK/RANKL
      system, might be to activate osteoclast differentiation in these cells.

PMID- 18345404
TI  - [Contribution of computed tomography in patients with lung metastases of
      differentiated thyroid carcinoma not apparent on plain radiography who were
      treated with radioiodine].
AB  - Computed tomography (CT or CAT Scan) of the chest is more sensitive than
      radiography in the detection of lung metastases of differentiated thyroid cancer
      (DTC), but little information is available regarding the aggregated value of this
      method. The present study evaluated the response of patients with lung metastases
      of DTC not apparent on radiography to treatment with 131I and the value of CT in
      these cases. Twenty-five patients with lung metastases not apparent on
      radiography, who initially received 100-200 mCi I151, were evaluated and those
      presenting pulmonary uptake on post-therapy WBS were submitted to a new treatment
      after 6 to 12 months, and so on. The chance of detection of pulmonary uptake on
      post-therapy WBS did not differ between patients with negative and positive CT
      (100% versus 91.5%). Mean serum Tg levels were higher in patients with positive
      CT (108 ng/ml versus 52 ng/ml). Negative post-therapy WBS was achieved in 82% of
      patients with positive CT and in 92.3% with negative CT and the cumulative I131
      activity necessary to achieve this outcome did not differ between the two groups
      (mean=300 mCi). Stimulated Tg was undetectable in 47% of patients with negative
      CT at the end of treatment, but in none of the patients whose CT continued to be
      positive. In patients with elevated Tg, the CT result apparently did not change
      the indication of therapy or the I131 activity to be administered. In cases with
      lung metastases, the persistence of micronodules on CT was associated with the
      persistence of detectable Tg in patients presenting negative post-therapy WBS.

PMID- 18345405
TI  - [Metformin and AMPK: an old drug and a new enzyme in the context of metabolic
      syndrome].
AB  - Metformin is one of the most commonly prescribed oral antidiabetic agents
      worldwide. However, its mechanism of action remains unknown. The Diabetes
      Prevention Program Research Group studies have shown that metformin
      administration and lifestyle-intervention (diet and exercise) reduce the
      incidence of Diabetes Mellitus type 2 (DM2). A possible biochemical connection
      between both therapies may be the AMP-activated protein kinase (AMPK). This
      enzyme was originally described as a sensor of cellular energy status, being
      activated in exercise. On the other hand, several experimental evidences indicate
      that AMPK may be an important target of metformin action. This paper discusses
      various ways for AMPK regulation, suggesting a possible mechanism for its
      activation by metformin that involves the production of reactive nitrogen
      species. AMPK activation determines a wide variety of physiological effects,
      including enhanced glucose uptake by skeletal muscle and enhanced lipid
      catabolism. Thus, it may be a key player not only in the prevention and treatment
      of DM2, but also in the development of new treatments for obesity and the
      metabolic syndrome. The finding of AMPK activation by metformin draws attention
      to this enzyme as an important pharmacological target.

PMID- 18345406
TI  - [Transient neonatal hypothyroidism due to amiodarone administration during
      pregnancy--two cases report and review of literature].
AB  - INTRODUCTION: Amiodarone (AMD) is an antiarrhythmic agent which contains 37% of
      iodine. It can reach the fetus by transplacental passage and induce transient
      congenital hypothyroidism (TCH). We report two cases of TCH caused by gestational
      exposure to AMD, detected by the Newborn Screening Program for Congenital
      Hypothyroidism of the State of Parana-Brazil. CLINICAL CASE 1 (C1): Neonatal TSH
      value was 78.2 mU/L (normal<15 mU/L). AMD had been given to the mother during
      pregnancy to treat maternal arrhythmia. The screening results were confirmed by
      serum thyroid function tests. Levothyroxin (L-T4) (50 microg/day) was started on
      the first visit, on the 14th day of life (dl). CLINICAL CASE 2 (C2): Neonatal TSH
      value was 134.0 mU/L. AMD had been given to the mother in the third trimester of
      pregnancy to treat maternal arrhythmia. The screening results were confirmed by
      serum thyroid function tests: L-T4 (50 microg/day) was started on the first
      visit, with 13 dl. FOLLOW-UP: TSH and T4 normalized on 51 dl (C1) and 36 dl (C2);
      L-T4 could be diminished gradually and stopped within 16 months (C1) and 10
      months (C2). They were followed-up until 22 months (C1) and 16 months (C2) with
      normal thyroid function tests. Their growth and mental development, evaluated by
      the Cognitive Adaptive Test/Clinical Linguistic & Auditory Milestone Scale
      (CAT/CLAMS test), were normal. CONCLUSION: Evaluation of thyroid function and
      mental development should be performed if AMD is used during pregnancy. Treatment
      of TCH must be started as soon as the diagnosis is made.

PMID- 18345407
TI  - [Neurofibroma of thyroid in a patient with neurofibromatosis type 1].
AB  - The neurofibromatosis type 1 (NF1), also known as von Recklinghausens disease, is
      an autosomal dominant disorder, with high degree of variability of clinical
      expression, usually involved with formation of tumors, with benign origin in the
      majority of cases mainly localized in the region of the head and neck and rarely
      incident in the thyroid area. However, the association with medullary carcinoma
      of the thyroid (MCT) exists in literature and needs to be excluded. We report a
      case of a patient with NF1, nonfunctional thyroid nodule and obstructive
      symptoms. Surgical resection of lesion was performed, with histopathologic
      findings compatible with neurofibroma in thyroid tissue. This case is relevant
      not only because of the rarity of the presentation of NF1, but also due to the
      likely association with MCT, an aggressive tumor that can be cured by surgery.

PMID- 18345408
TI  - [Diabetes insipidus in a pacient with multiple sclerosis].
AB  - Multiple Sclerosis (ME) is a chronic progressive disease characterized by
      relapses of demyelination that can occur anywhere in the brain stem, spinal cord
      and optic nerve. Since central diabetes insipidus (DI) is mainly caused by
      central nervous system damage (such as trauma, surgery, tumor, infection,
      sarcoidosis), ME is included among its possible etiologies. However, this
      association is not commonly described. The clinical suspicion must be made in the
      presence of polyuria and polydipsia or refractory hypernatremia (in patients
      without free access to water) during the evolution of ME. We will describe a
      clinical report in which this association occurred and, after the beginning of
      desmopressin therapy, the clinical findings were reverted.

PMID- 18345409
TI  - Octreotide-LAR-associated erythema multiforme in an acromegalic subject: case
      report.
AB  - Long-acting somatostatin analogs are often used for treating acromegaly, either
      as adjuvant to surgery or radiotherapy or, more recently, as a primary
      therapeutic option. These drugs seem to be reasonably safe, but new adverse
      effects not yet described may occur during the use of the relatively new long
      acting formulations. In this case report, we describe a severe cutaneous reaction
      (erythema multiforme) in a patient treated with long-acting release (LAR)
      octreotide, and also discuss the need of previous "testing" with short
      subcutaneous preparation of octreotide.

PMID- 18345410
TI  - [Should we change the reference values of normal TSH?].

PMID- 18345411
TI  - Hippocampal sclerosis and status epilepticus: cause or consequence? A MRI study.
AB  - BACKGROUND: Transient imaging abnormalities, including changes on diffusion
      weighted imaging (DWI), may be seen in status epilepticus. These abnormalities
      can be followed by hippocampal sclerosis. CASE REPORT: We report a 15-year-old
      lady with focal non convulsive status epilepticus (NCSE) and focal slowing on
      EEG. DWI exhibited abnormal hyperintense signals in bilateral temporal and
      insular cortices. After 3 weeks, MRI performed a localizated hippocampal atrophy.
      CONCLUSION: The MRI findings indicated vasogenic and cytotoxic edema during
      seizure activity and subsequent loss of brain parenchyma.

PMID- 18345412
TI  - Dendritic right/left asymmetries in the neurons of the human hippocampal
      formation: a quantitative Golgi study.
AB  - OBJECTIVE: To search for right/left asymmetries in the dendritic trees of the
      neuronal populations and in the cell-free layer volumes of the human hipoccampal
      formation. METHOD: In necropsic material obtained from six male individuals we
      performed a quantitative Golgi study of the dendritic trees of dentate granules,
      CA3 and CA1 pyramidal neurons and a volumetric analysis of dentate gyrus
      molecular layer, strata oriens plus alveus and strata lacunosum-moleculare plus
      radiatum of CA3 and CA1 fields. RESULTS: We found inter-hemispheric asymmetries
      in the dendrites trees of all neurons, reaching the significant level in the
      number of granule cells dendritic segments (higher in the left than in the right
      hemisphere), dendritic branching density of CA3 pyramidal cells and mean
      dendritic length of CA1 apical terminal segments (higher in the right than in the
      opposite side). No volumetric differences were observed. CONCLUSION: This study
      points to different anatomical patterns of connectivity in the hippocampal
      formations of both hemispheres which may underlie functional asymmetries.

PMID- 18345413
TI  - Immunoexpression of tumor suppressor genes p53, p21 WAF1/CIP1 and p27 KIP1 in
      humam astrocystic tumors.
AB  - The aim of the present study was to evaluate the tumor suppressor genes p53, p21
      WAF1/CIP1 and p27 KIP1 expression in astrocytic tumors, correlating the findings
      with the histopathological grade (WHO). An immunohistochemical study of the p53,
      p21 and p27 proteins using the streptavidin-biotin-peroxidase method was
      performed in fifty-five astrocytomas (13 grade I, 14 grade II, 7 grade III and 21
      grade IV) and five samples of non-tumor brain tissue (negative control). p53
      positive indices (PI) and labeling indices (LI) showed tendency to increase
      according to malignant progression. The nuclear expression of p27 presented
      similar inclination, except for the PI reduction verified in grade IV tumors.
      Otherwise, the cytoplasmic p27 staining was more evident between high-grade
      tumors (III and IV). p53 and nuclear p27 expression was correlated with the
      histological classification (p<0.01; test H). On the other hand, p21 indices
      revealed a propensity to reduction in agreement with malignant evolution of the
      astrocytic tumors, except for high scores observed in grade IV tumors. The non
      tumor samples did not show any expression of these proteins. These results
      indicated the p53 mutation as an initial, relevant and potentially predictor of
      tumor progression event in astrocytomas, with the detection of p21 protein as an
      important resource for the deduction of functional situation of this gene.
      Moreover, the activation of p27 KIP1 was preserved in the astrocytic tumors and
      its cytoplasmic manifestation seems to be resultant of its nuclear expression,
      not demonstrating a direct impact in astrocytomas tumorigenesis.

PMID- 18345414
TI  - Prevalence of HLA DQB1*0602 allele in patients with migraine.
AB  - BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic
      patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with
      narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual
      aura has raised greater awareness of the genetic background in migraine. PURPOSE:
      Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we
      hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of
      migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy
      subjects with no history of migraine, 53 patients with migraine without aura and
      52 patients with migraine with aura. RESULTS: There was no difference in the
      frequency of HLA DQB1*0602 allele when control subjects and all patients were
      compared. We failed to note any difference in frequencies when comparing migraine
      patients with and without aura. CONCLUSION: Further studies with different
      patient populations, with other hypothalamic markers (melatonin, hypocretin) in
      migraine patients may shed light on to its pathophysiology.

PMID- 18345415
TI  - Chronic daily headache: stress and impact on the quality of life.
AB  - OBJECTIVE: To evaluate the stress presence and its influence in the quality of
      life of patients with chronic daily headache (CDH). METHOD: A hundred patients
      with at least 18 years old, with primary headache with duration greater than 4
      hours a day, and frequency of 15 or more days monthly for at least three months
      were studied. Lipp's Inventory of Stress Symptoms and the Medical Outcomes Study
      Short Form (SF-36) were used. RESULTS: Stress was observed in 90% of the
      patients; nearly half of them was in the phase almost exhaustion. Patients with
      stress when compared with the ones with no stress presented significantly lower
      scores in all the domains of SF-36; except in physical functioning. The
      resistance phase presented scores significantly higher than almost exhaustion;
      except for bodily pain. CONCLUSION: The majority of the patients presented stress
      with significant reduction in their quality of life. Consequently, the stress
      could be related with both the development and the maintenance of CDH.

PMID- 18345416
TI  - Clinical features, diagnosis and treatment of acute primary headaches at an
      emergency center: why are we still neglecting the evidence?
AB  - In order to analyze the clinical features, approach and treatment of patients
      with acute primary headaches seen at the Clinics Hospital of the Federal
      University of Uberlandia (HC-UFU) throughout 2005, the medical charts of 109
      patients were evaluated through a standardized questionnaire as to age, gender,
      main diagnosis, characteristics of the headache attacks, diagnostic tests and
      treatment. Probable migraine was the most common type of primary headache
      (47.7%), followed by probable tension-type headache (37.6%), unspecified headache
      (11.9%), and headache not elsewhere classified (2.8%). As to characteristics of
      the crisis, the location of the pain was described in 86.2% of the patients. The
      most commonly used drugs for treatment of acute headache attacks were dipyrone
      (74.5%), tenoxicam (31.8%), diazepam (20.9%), dimenhydrate (10.9%), and
      metochlopramide (9.9%). The data collected are in agreement with those reported
      in literature. In most cases, treatment was not what is recommended by consensus
      or clinical studies with appropriate methodology. Therefore, we suggest the
      introduction of a specific acute headache management protocol which could
      facilitate the diagnosis, treatment and management of these patients.

PMID- 18345417
TI  - Study of the positivity of spontaneous and directed diagnosis of leukoaraiosis in
      the elderly by cranial computerized tomography, and its correlation with
      cognitive deficit and cardiovascular risk factors.
AB  - OBJECTIVE: To evaluate the prevalence of leukoaraiosis (LA) and its correlation
      with vascular risk factors and the cognitive performance of elderly patients.
      METHOD: 78 patients were randomly selected and submitted to clinic-laboratorial
      evaluation for vascular risk factors. Two cognitive tests were performed. All
      patients were submitted to cranial computerized tomography (CT), which was
      analyzed in two situations: the spontaneous and the directed way. RESULTS: There
      was no statistically significant difference between the prevalence of spontaneous
      and the directed diagnoses of LA (20.5 and 18%, respectively). The presence of LA
      was not significantly correlated with cognitive impairment. Only age was
      positively associated with LA. CONCLUSION: Cranial CT is a trustworthy method for
      the diagnosis of LA. Only age showed a positive association. No clinical
      implications were found, concerning the cognitive performance of the patients.

PMID- 18345418
TI  - Frequency of stroke types at an emergency hospital in Natal, Brazil.
AB  - We performed a cross-sectional study of stroke type frequency at a local
      emergency hospital, in Natal, Brazil. The sample consisted of all patients who
      were admitted to an emergency hospital with a presumptive diagnosis of stroke. Of
      the 416 patients, 328 were studied, 88 were excluded for not meeting inclusion
      criteria, 74.7% (n= 245) had ischemic stroke 17.7% (n=58) had intracerebral
      hemorrhage, 7.6% (n=25) had subarachnoid hemorrhage; 173 were men (52.7%). Mean
      age was 64.1 years. The intrahospital mortality rate was 10.2%, 17.2% and 36% for
      ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage,
      respectively. The most prevalent modifiable risk factor was hypertension for
      ischemic stroke (67.6%) and hemorrhage stroke (57.8%). Logistic regression
      analysis identified diabetes (OR=3.70; CI=1.76-7.77) as independent risk factor
      for ischemic stroke. The ischemic stroke was most common type of stroke.
      Hypertension and diabetes were important risk factors for stroke.

PMID- 18345419
TI  - Magnetic resonance spectroscopy in the diagnosis and etiological definition of
      brain bacterial abscesses.
AB  - We report two patients with bacterial brain abscesses whose etiological diagnosis
      was correctly proposed by association of diffusion weighted images (DWI) and
      magnetic resonance spectroscopy (MRS) with conventional MRI. Both patients
      presented ring enhancing lesions with evidences of restricted diffusion. On MRS,
      the abscess caused by aerobic bacteria presented lactate and aminoacids peaks and
      the abscess caused by anaerobic facultative bacteria showed also acetate and
      succinate peaks. These results are in agreement with an unique previous study
      that related MRS pattern with bacterial etiology. Conventional MRI, associated
      with DWI and MRS is effective in diagnosing bacterial abscess and promising in
      exploring its etiology.

PMID- 18345420
TI  - Clinical outcome of neonatal bacterial meningitis according to birth weight.
AB  - OBJECTIVE: To describe the clinical outcome and the complications of bacterial
      meningitis according to birth weight of out born neonates admitted in intensive
      care unit during an 11 year-period. METHOD: Eighty-seven newborns were studied.
      Thirty-four infants were low birth weight newborn and 53 presented birth weight
      >or= 2500 g. The clinical data were obtained through the analysis of patients
      files. Fishers exact test, the c2 and the Mann-Whitney test were applied.
      RESULTS: Neurological symptoms were more common in infants weighed >or= 2500 g
      (p<0.05). Complications affected half of the cases in both groups. Complications
      affected half of the cases in both groups, with an overall mortality rate of
      11.5%. CONCLUSION: The rate of complications was high in both groups, regardless
      of the birth weight. No association was observed between the occurrence of death
      and birth weight. Infants with positive CSF culture had a poorer prognosis.

PMID- 18345421
TI  - Subclinical encephalopathy in chronic obstructive pulmonary disease.
AB  - BACKGROUND: Clinical and experimental evidence suggests that chronic obstructive
      pulmonary disease (COPD) is associated with a variety of mental symptoms that
      range from cognitive slowing to mental confusion and dementia. PURPOSE: To test
      the hypothesis that COPD leads to cognitive impairment in the absence of acute
      confusion or dementia. METHOD: The global cognitive status of 30 patients with
      COPD without dementia or acute confusion and 34 controls was assessed with a
      Brazilian version of the Mini-Mental State Exam (MMSE). RESULTS: The MMSE scores
      were significantly lower in the patient group and inversely related to the
      severity of COPD. This finding could not be attributed to age, education, gender,
      daytime sleepiness, hypoxemia, chronic tobacco use, or associated diseases such
      as diabetes, depression, high blood pressure or alcoholism. CONCLUSION: These
      results suggest the existence of a subclinical encephalopathy of COPD
      characterized by a subtle impairment of global cognitive ability.

PMID- 18345422
TI  - Vasopressin serum levels and disorders of sodium and water balance in patients
      with severe brain injury.
AB  - BACKGROUND: Disorders of water and sodium balance are frequently seen in patients
      with severe brain injury (SBI), and may worsen their prognosis. PURPOSE: To
      evaluate vasopressin (AVP) serum levels and sodium and water balance disorders
      during the first week post-injury in patients with SBI. METHOD: Thirty-six adult
      patients with SBI (admission Glasgow Coma Scale score < or= 8) and an estimated
      time of injury <or= 72 hours were prospectively studied. Clinical and laboratory
      data were recorded and AVP was measured in venous blood samples collected on the
      1st, 2nd, 3rd and 5th days following inclusion. RESULTS: AVP serum levels
      remained within the normal range in SBI patients (either traumatic or non
      traumatic), although tended to be greater in non-survivor than in survivor
      patients (p=0.025 at 3rd day). In-hospital mortality was 43% (15/36), and serum
      sodium and plasma osmolality variabilities were greater in non-survivor than in
      survivor patients during the observation period (p<0.001). CONCLUSION: AVP serum
      levels remained within the normal range values in these SBI patients, but those
      who died have shown higher incidence of abnormal sodium and water balance during
      the first week post-injury.

PMID- 18345423
TI  - Transoral approach to the craniovertebral junction.
AB  - The transoral approach provides a safe exposure to lesions in the midline and the
      ventral side of the craniovertebral junction. The advantages of the transoral
      approach are 1) the impinging bony pathology and granulation tissue are
      accessible only via the ventral route; 2) the head is placed in the extended
      position, thus decreasing the angulation of the brainstem during the surgery; and
      3) surgery is done through the avascular median pharyngeal raphe and clivus. We
      analyzed the clinical effects of odontoidectomy after treating 38 patients with
      basilar invagination. The anterior transoral operation to treat irreducible
      ventral compression in patients with basilar invagination was performed in 38
      patients. The patients ages ranged from 34 to 67 years. Fourteen patients had
      associated Chiari malformation and eight had previously undergone posterior
      decompressive surgery. The main indication for surgery was significant
      neurological deterioration. Symptoms and signs included neck pain, myelopathy,
      lower cranial nerve dysfunction, nystagmus and gait disturbance. Extended
      exposure was performed in 24 patients. The surgery was beneficial to the majority
      of patients. There was one death within 10 days of surgery, due to pulmonary
      embolism. Postoperative complications included two cases of pneumonia, three
      cases of oronasal fistula with regurgitation and one cerebrospinal fluid leak. In
      patients with marked ventral compression, the transoral approach provides direct
      access to the anterior face of the craniovertebral junction and effective means
      for odontoidectomy.

PMID- 18345424
TI  - Interlaminar epidural corticosteroid injection in the treatment of lumbosciatic
      pain: a retrospective analysis.
AB  - Lumbosciatica is a common condition which is associated with significant pain and
      disability. The aim of the present study was to examine the efficacy of
      interlaminar epidural corticosteroid infiltration in the treatment of
      lumbosciatic pain. We evaluated retrospectively sixty patients with lumbosciatic
      pain that a sequential interlaminar epidural administration of 40 mg
      methylprednisolone in 7 mL bupivacaine 0.25% was administered. Each patient was
      interviewed and asked about the pain according to visual analogue scale (VAS) and
      the level of disability according to World Health Organization previously of the
      epidural corticosteroid infiltration and, 1 and, 6 months after starting therapy.
      Independently of the initial VAS value, all patients decreased their pain score
      after one and six months of follow-up (p<0.05). However, only the patients with a
      low grade of disability showed an improvement after the treatment (p<0.05). No
      side effects were reported after epidural corticosteroid injections. In
      conclusion, interlaminar epidural corticosteroid injection in association with
      local anesthetic may be useful, at least for six months, as additional therapy of
      the conservative management of lumbosciatic pain.

PMID- 18345425
TI  - Bipolar disorder and multiple sclerosis.
AB  - Bipolar disorder may be overrepresented in multiple sclerosis (MS) patients.
      Although research in this area is limited, studies assessing the nature of this
      association have focused on genetic aspects, adverse reaction to drugs and brain
      demyelinating lesions. Herein we report three patients with MS that also
      presented bipolar disorder. The coexistence of neurological and psychiatric
      symptoms in most MS relapses highlights the relevance of biological factors in
      the emergence of mood disorders in these patients.

PMID- 18345426
TI  - Knowledge and attitudes toward epilepsy amongst students in the health area:
      intervention aimed at enlightenment.
AB  - It is known that there is a lack of knowledge about epilepsy amongst the
      population in general, with consequent prejudice and discrimination towards
      epileptic patients. Considering the importance of health professionals in the
      diffusion of knowledge about this neurological condition, the objective of the
      present study was to evaluate modifications in the knowledge and attitudes of
      students in the health area with respect to epilepsy, after an intervention
      including the presentation of specific audio-visual material and a discussion on
      the basic aspects of epilepsy. Simple self-administered questionnaires were
      applied to one hundred and sixteen health area students before and after the
      session of enlightenment. After the session there was significant (p<0.05)
      improvement in answers to different questions about etiology, epidemiology,
      education, work, and attitude during the seizure. The results suggest the need to
      include a routine low complexity educational activity in the curriculum of
      various courses in the health area.

PMID- 18345427
TI  - Awareness, attitudes and perceptions on epilepsy in Southern Brazil.
AB  - OBJECTIVE: To verify awareness and attitudes toward epilepsy in Southern Brazil.
      METHOD: A questionnaire about familiarity with the disease, awareness and
      attitudes toward epileptics was applied to 832 inhabitants of Caxias do Sul. The
      answers were analyzed in three different groups: G1, non-university students; G2,
      university students up to the second year; and G3, university students with more
      than two years education and university graduates. RESULTS: University students
      and graduates are better informed regarding causes and treatment of epilepsy.
      Moreover, those interviewees present less negative attitudes toward epileptics.
      However, a large part of that group lacks some basic information on the disease.
      CONCLUSION: There is lack of information on epilepsy among Brazilians. Education
      campaigns should be carried out in order to clarify some aspects concerning
      epilepsy.

PMID- 18345428
TI  - Screening tests are not enough to detect hemineglect.
AB  - OBJECTIVE: To verify the sensitivity of the conventional subtests of the
      Behavioral Inattention Test (BIT) in the diagnosis of hemineglect after stroke.
      METHOD: One hundred and two patients with cerebral infarct or hemorrhage were
      prospectively evaluated. In 22, hemineglect was diagnosed using standard BIT
      criteria. The frequency of hemineglect using 6 commonly used screening subtests
      of this battery was assessed. RESULTS: Hemineglect would not be recognized in 10
      patients if they were only screened using the line crossing test; this would be
      the case in 2 patients with the letter cancellation test; and in 4 patient with
      the line bisection test. Three patients would not be diagnosed even if both line
      crossing and line bisection tests were used. CONCLUSION: Hemineglect may not be
      recognized with single screening tests commonly used. The use of a standard
      battery is recommended to improve diagnostic sensitivity in individuals with
      various subtypes of hemineglect.

PMID- 18345429
TI  - [Headache and systemic lupus erythematosus: prevalence and associated
      conditions].
AB  - OBJECTIVE: To study the prevalence of headache in patients with systemic lupus
      erythematosus (SLE) and normal population as well as associated conditions.
      METHOD: Forty nine SLE patients and 50 controls were analyzed for presence of
      headaches (tensional and migraine). In the SLE group, we studied the occurrence
      of Raynaud, teleangiectasis, cutaneous vasculitis, convulsions and
      antiphospholipid antibodies. RESULTS: Among SLE patients, 42 had headaches
      (85.7%), 29 with migraine and 13 tensional; on the control group, 28 had
      headaches (57.1%), 18 migraine and 10 tension type with p=0.0026 for migraine. In
      SLE patients we did not find any association between migraine and Raynaud
      (p=0.34), teleangiectasis (p=0.77), cutaneous vasculitis (p=0.63), seizures
      (p=0.13), aCl IgG (p=0.45), IgM (=0.07) and LAC (p=0.59). CONCLUSION: Migraine is
      more prevalent in the SLE population. However, it has no relationship with
      Raynaud, teleangiectasis, seizures, cutaneous vasculitis and antiphospholipid
      antibodies.

PMID- 18345430
TI  - [Smell recognition in pervasive developmental disorders].
AB  - AIM: To evaluate smell recognition in pervasive developmental disorders (PDD).
      METHOD: Twenty-one PDD (experimental group) and 21 matched controls (control
      group) male adolescents were submitted to a standardized, 12-stimuli, smell
      battery in three moments: with no identification suggestion; associated to four
      linguistic alternatives for each stimulus, and submitted again, 25 days after,
      with no linguistic alternatives. Data was analyzed by t test and variance
      analysis (p=0,05). RESULTS: The experimental group scored worse than control
      group. Both groups scored better after stimuli and, after 25 days, scores
      lowered, but stayed higher than initially, without any stimuli (p<0,001). The gap
      was higher after 25 days, when the experimental group showed poorer smell memory
      from initial presentation (p<0,001). CONCLUSION: The experimental group showed
      lower recognition scores, unrelated to clues previously offered, which suggests a
      difficulty in phenomena and semantic meaning association. Even after matching
      odors nomination, the gap of recognition scores remains between groups, not only
      in a deficitary pattern, but also qualitatively disturbed.

PMID- 18345431
TI  - [Relation between the resistance index obtained by the transfontanellar Doppler
      ultrasonography and the neurological development until the first year of life in
      term infants with mild or moderate hypoxic-ischaemic encephalopathy].
AB  - OBJECTIVE: To evaluate the relation between the resistance index (RI) obtained by
      transfontanellar Doppler ultrasonography, and the neurodevelopment until one year
      of life, at term newborns with mild or moderate hypoxic-ischaemic encephalopathy
      due to intrapartum asphyxia. METHOD: 20 term newborns, with mild or moderate
      hypoxic-ischemic encephalopathy, high values of resistance index in the first
      exam, and without cerebral morfologic abnormalities or other diseases. They were
      submitted to serial bimonthly transfontanellar Doppler ultrasonography, from the
      seventh day of life on, and monthly clinical neurodevelopment assessment until
      one year of life. RESULTS: There was a progressive normalization of RI values
      until the last examination. In five cases there were clinical neurologic
      normalization in the neonatal period after the first Doppler exam. Fifteen
      infants presented neurologic abnormalities, with normalization after the second
      trimester of life. CONCLUSION: There was a relation between the normal RI values
      with the normalization of the clinical assessment.

PMID- 18345432
TI  - [Brain tumors and pregnancy].
AB  - BACKGROUND: Despite not being a common fact, the occurrence of brain tumors
      during pregnancy poses a risk to both the mother and infant. AIM: To identify the
      best medical procedure to be followed for a pregnant patient harboring a brain
      tumor. METHOD: The records of 6 patients with brain tumors, diagnosed during
      pregnancy were examined. RESULTS: Several types of brain tumors have been
      associated with pregnancy, but the meningioma is, by far, the most frequent. It
      seems that pregnancy aggravates the clinical course of intracranial tumors. There
      were no operative mortality in these series. In 2 patients the labor occurred
      before the craniotomy and in others, the delivery occurred after the surgery.
      CONCLUSION: The best moment to recommend the craniotomy and the neurosurgical
      removal of the tumor will depend of the mothers neurological condition, the tumor
      histological type as well as the gestational age.

PMID- 18345433
TI  - Total agenesis of the corpus callosum in a patient with childhood-onset
      schizophrenia.
AB  - The hypothesis that schizophrenia involves aberrant inter-hemispheric
      communication has a long pedigree, however its precise role remains unclear. We
      therefore report the case of a total agenesis of the corpus callosum in a 21-year
      old man with childhood-onset schizophrenia. The presence of schizophrenia with
      very early onset on absence of corpus callosum offers an opportunity to examine
      neurodevelopmental model and theories regarding to interhemispheric communication
      in the pathogenesis of psychosis.

PMID- 18345434
TI  - Broca's aphemia: an illustrated account of its clinico-anatomic validity.
AB  - OBJECTIVE: To present the case of a 54-year-old man with loss of speech, but with
      preservation of voluntary facio-lingual motility, language and other cognitive
      abilities (Broca's aphemia). METHOD: Observation of patient oral communicative
      abilities and general behavior, neuropsychological assessment and cranial
      computed tomography. RESULTS: Computed tomography showed a hyperdense lesion in
      the subcortex of the left precentral gyrus corresponding to Brodmann's area 6 and
      44. Neuropsychological assessment confirmed that the major cognitive domains were
      intact. CONCLUSION: Our patient reiterates the validity of Broca's aphemia as a
      clinico-anatomic entity allowing us to portray it for the first time in pictures.
      From a neurobehavioral perspective, aphemia is related to apraxia rather than to
      aphasia, a fact that may have hampered the full grasp of its far-reaching
      implications for neurology and aphasiology.

PMID- 18345435
TI  - A novel missense mutation pattern of the GCH1 gene in dopa-responsive dystonia.
AB  - Dopa-responsive dystonia (DRD) is an inherited metabolic disorder now classified
      as DYT5 with two different biochemical defects: autosomal dominant GTP
      cyclohydrolase 1 (GCH1) deficiency or autosomal recessive tyrosine hydroxylase
      deficiency. We report the case of a 10-years-old girl with progressive
      generalized dystonia and gait disorder who presented dramatic response to
      levodopa. The phenylalanine to tyrosine ratio was significantly higher after
      phenylalanine loading test. This condition had two different heterozygous
      mutations in the GCH1 gene: the previously reported P23L mutation and a new Q182E
      mutation. The characteristics of the DRD and the molecular genetic findings are
      discussed.

PMID- 18345436
TI  - Impacted cisterna magna without syringomyelia associated with lancinating
      headache, throbbed nuchal pain and paraparesis treated byposterior fossa
      decompression.
AB  - A 29-year-old woman with acute lancinating headache, throbbed nuchal pain and
      subacute paraparesis underwent brain MRI in supine position that depicted: the
      absence of the cisterna magna, filled by non herniated cerebellar tonsils and
      compression of the brain stem and cisternae of the posterior fossa, which are
      aspects of the impacted cisterna magna without syringomyelia and without
      hydrocephalus. During eight days, pain was constant and resistant to drug
      treatment. Osteodural-neural decompression of the posterior fossa, performed with
      the patient in sitting position, revealed: compression of the brainstem, fourth
      ventricle and foramen of Magendie by herniated cerebellar tonsils, which were
      aspirated. Immediately after surgery, the headache and nuchal pain remmited. MRI
      depicted the large created cisterna magna and also that the cerebellar tonsils
      did not compress the fourth ventricle, the foramen of Magendie and the brainstem,
      besides the enlargement of posterior fossa cisternae. Four months after surgery,
      headache, nuchal pain and paraparesis had disappeared but hyperactive patellar
      and Achilles reflexes remained.

PMID- 18345437
TI  - Glossopharyngeal neuralgia with syncope as a sign of neck cancer recurrence.
AB  - Glossopharyngeal neuralgia with syncope as a sign of neck cancer is a very rare
      condition. A review of the literature revealed only 29 cases formerly reported.
      We present the first Brazilian case of such association. A 68-year-old man
      presented with paroxysmal excruciating pain over the right side of the neck,
      sometimes followed by syncope. Given the suspicion of recurrent tumor from a
      previously treated neck malignancy, a computed tomography scan was performed and
      a right parapharyngeal tumor was shown. Pain and syncope were successfully
      controlled with carbamazepine and the patient underwent palliative radiotherapy.

PMID- 18345438
TI  - Bilateral cortical atrophy after severe brain trauma and extradural homatoma.
AB  - We report the case of a severe head injured 43-year old male patient with a large
      extradural hematoma, Glasgow Coma Scale 3 and dilated fixed pupils. Patient was
      promptly submitted to surgical evacuation of the lesion, but remained in
      persistent vegetative state in the post-operative time. Head computed tomography
      scans performed before surgery, and at early and late post-operative periods
      comparatively revealed extreme bilateral cortical atrophy. Late consequences of
      severe head trauma drastically affect the prognosis of patients, being its
      prevention, and neuroprotection against secondary injury still a therapeutical
      challenge for neurosurgeons.

PMID- 18345439
TI  - Idiopathic inflammatory pseudotumor of the carotid sheath.
AB  - We present a biopsy proven case of 47 years-old man with a carotid pseudotumor,
      clinically presented as carotidynia. CT showed a mass encasing and narrowing the
      common carotid artery and MRI showed hypointense signal in T2 and intense
      enhancement after contrast media administration. The patient was suspected to
      have an inflammatory process and steroids were prescribed. Eight days after the
      steroid treatment significant radiological and clinical improvement was observed.
      The patient remains free of symptoms.

PMID- 18345440
TI  - True neurogenic thoracic outlet syndrome in a competitive swimmer: a case report
      of this rare association.
AB  - True neurogenic thoracic outlet syndrome (TOS) is an uncommon disorder despite of
      be a frequent reason for referral to the EMG laboratories. We describe the second
      case in the literature of true TOS in a competitive swimmer with progressive
      weakness and severe atrophy of the left thenar eminence. EMG showed lower trunk
      plexopathy. X-ray and MRI of the cervical spine and brachial plexus were normal.
      Surgical exploration evidenced the lower trunk retracted and pulled by a fibrous
      band. It was excised and neurolysis of the plexus was done with gradual
      improvement of function. We discuss the possible pathophysiology of this
      association.

PMID- 18345441
TI  - Early surgery for ruptured cerebral aneurysms: technical note.
AB  - We describe a collection of techniques to be considered in the early clipping of
      ruptured cerebral aneurysms located in the anterior circulation when dealing with
      the swollen red and scaring brain many times found after craniotomy.

PMID- 18345442
TI  - Dom Joao VI's death: convulsions and coma.
AB  - Dom Joao VI's death occurred in adverse political conditions that led to the
      regicide hypothesis. The main aim of this paper is to mention life style and
      conditions of the death of the king by means of narrative review based on primary
      and secondary sources. Dom Joao VI died in the way of convulsions and
      gastrointestinal symptoms. This could be the result of the pathological chain of
      genetic determination, accentuated by the inappropriate life style, obesity and
      sedentary habits, and/or poisoning. The finding of arsenic in high doses in his
      viscera favors the last hypothesis as the basic cause of death, but one can not
      discard the atherosclerosis predisposing risk factors for a final stroke.

PMID- 18345443
TI  - The Emperor Dom Pedro II: his convulsive seizures when a boy.
AB  - INTRODUCTION: Dom Pedro II, the Prince Heir and Emperor under regency, in a
      delicate period of the construction of the Brazilian nation, had convulsive
      seizures. OBJECTIVE: To investigate the convulsive seizures and related syndromes
      of Dom Pedro II and his family, besides the physicians in charge of the health
      care. METHOD: Narrative review based on primary and secondary sources.
      CONCLUSION: The scattered and self-limited convulsive seizures associated with
      physical and mental integrity favored a benign prognosis. Dom Pedro and his
      family presented rich history of epileptic seizures and febrile convulsion. This
      variety resembles the diagnosis of generalized epilepsy with febrile seizures
      plus that seems to be a combination of several syndromes with shared genetic
      susceptibility.

PMID- 18345444
TI  - The decline of Dom Pedro II's empire and health: neuropathogenic implications.
AB  - The main objective of this paper is to know the medical doctors of the Emperor,
      the preconized treatment, and the knowledge about diabetes at that time, its
      repercussions on the Emperor's nervous system, and the related political
      implications. A narrative revision was made, based on primary and secondary
      sources. Dom Pedro II was examined by the aristocracy of the medicine at the
      time, especially Jean-Martin Charcot, amongst the doctors of international
      reputation, and Claudio Velho da Motta Maia, amongst the Brazilian doctors.
      Charcot diagnosed in the Monarch: mental stress, diabetic neuropathy, and a
      cerebral vascular lesion, probably a stroke, that he differentiated from other
      vascular obliterations elsewhere. He demonstrated his knowledge about diabetic
      neuropathy, possible topographical alternatives to justify the urinary
      incontinence, and Dom Pedro's weakness in the legs. Throughout his illness, Dom
      Pedro II presented others manifestations that contributed to his physical
      fragility, and that, certainly too, to his political decline, deposition and the
      proclamation of the Brazilian Republic.

PMID- 18345445
TI  - Juvenile myoclonic epilepsy.
AB  - Juvenile myoclonus epilepsy (JME) is a common epileptic syndrome, the etiology of
      which is genetically determined. Its onset occurs from 6 through 22 years of age,
      and affected patients present with myoclonic jerks, often associated with
      generalized tonic-clonic seizures - the most common association - and absence
      seizures. JME is non-progressive, and there are no abnormalities on clinical
      examination or intellectual deficits. Psychiatric disorders may coexist.
      Generalized polyspike-and-waves are the most characteristic
      electroencephalographic pattern. Usual neuroimaging studies show no
      abnormalities. Atypical presentations should be entertained, as they are likely
      to induce misdiagnosis. Prevention of precipitating factors and therapy with
      valproic acid (VPA) are able to control seizures in the great majority of
      patients. Whenever VPA is judged to be inappropriate, other antiepileptic drugs
      such as lamotrigine may be considered. Treatment should not be withdrawn,
      otherwise recurrences are frequent.

PMID- 18345446
TI  - Focal and multifocal diabetic neuropathies.
AB  - Diabetic neuropathy is the most common neuropathy in industrialized countries,
      with a remarkable range of clinical manifestations. The vast majority of the
      patients with clinical diabetic neuropathy have a distal symmetrical form that
      progress following a fiber-length dependent pattern, with predominant sensory and
      autonomic manifestations. This pattern of neuropathy is associated with a
      progressive distal axonopathy. Patients are exposed to trophic changes in the
      feet, pains and autonomic disturbances. Less often, diabetic patients may develop
      focal and multifocal neuropathy that includes cranial nerve involvement, limb and
      truncal neuropathies. This neuropathic pattern tends to occur after 50 years of
      age, mostly in patients with longstanding diabetes mellitus. The LDDP does not
      show any trend to improvement and either relentlessly progresses or remain
      relatively stable over years. Conversely the focal diabetic neuropathies, which
      are often associated with inflammatory vasculopathy on nerve biopsies, remain
      self limited, sometimes after a relapsing course.

PMID- 18345448
TI  - Pulmonary hypertension in chronic respiratory disorders: we need to learn more.

PMID- 18345449
TI  - Pulmonary histopathological alterations in patients with acute respiratory
      failure: an autopsy study.
AB  - OBJECTIVE: To present the pulmonary histopathological alterations found in the
      autopsies of patients with acute respiratory failure (ARF) and determine whether
      underlying diseases and certain associated risk factors increase the incidence of
      these histopathological patterns. METHODS: Final autopsy reports were reviewed,
      and 3030 autopsies of patients > 1 year of age with an underlying disease and
      associated risk factors were selected. All had developed diffuse infiltrates and
      died of ARF-related pulmonary alterations. RESULTS: The principal pulmonary
      histopathological alterations resulting in immediate death were diffuse alveolar
      damage (DAD), pulmonary edema, lymphocytic interstitial pneumonia (LIP) and
      alveolar hemorrhage. The principal underlying diseases were AIDS,
      bronchopneumonia, sepsis, liver cirrhosis, pulmonary thromboembolism, acute
      myocardial infarction (AMI), cerebrovascular accident, tuberculosis, cancer,
      chronic kidney failure and leukemia. The principal associated risk factors were
      as follows: age > 50 years; arterial hypertension; congestive heart failure;
      chronic obstructive pulmonary disease; and diabetes mellitus. These risk factors
      and AIDS correlated with a high risk of developing LIP; these same risk factors,
      if concomitant with sepsis or liver cirrhosis, correlated with a risk of
      developing DAD; thromboembolism and these risk factors correlated with a risk of
      developing alveolar hemorrhage; these risk factors and AMI correlated with a risk
      of developing pulmonary edema. CONCLUSION: Pulmonary findings in patients who
      died of ARF presented four histopathological patterns: DAD, pulmonary edema, LIP
      and alveolar hemorrhage. Underlying diseases and certain associated risk factors
      correlated positively with specific histopathological findings on autopsy.

PMID- 18345450
TI  - Foreign body aspiration in children: clinical aspects, radiological aspects and
      bronchoscopic treatment.
AB  - OBJECTIVE: To describe the clinical manifestations and bronchoscopic treatment of
      foreign body aspiration in children under 14 years of age, correlating the
      clinical aspects with the bronchoscopic findings. METHODS: A retrospective,
      descriptive study analyzing data related to children under 14 years of age
      undergoing bronchoscopy due to clinical suspicion of foreign body aspiration at
      the State University at Campinas Hospital das Clinicas from January of 2000 to
      December of 2005. RESULTS: The sample consisted of 69 patients, ranging in age
      from 8 months to 12 years/7 months (75.4% under 3 years of age), 62.3% of whom
      were male. The principal complaint was sudden-onset cough (75.4%), auscultation
      was abnormal in 74%, and dyspnea was observed in 29%. Radiological abnormalities
      were seen in 88% of the cases. Aspirations were primarily into the right lung
      (54.8%), and 30.7% of the foreign bodies were of vegetal origin (principally
      beans and peanuts). In the follow-up period, 29% presented complications (most
      commonly pneumonia), which were found to be associated with longer aspiration
      time (p = 0.03). Mechanical ventilation was required in 7 children (10.1%), and
      multiple bronchoscopies were performed in 5 (7.2%). CONCLUSION: A history of
      sudden-onset choking and cough, plus abnormal auscultation and radiological
      findings, characterizes the profile of foreign body aspiration. In such cases,
      bronchoscopy is indicated. Longer aspiration time translates to a higher the risk
      of complications. The high prevalence of foreign bodies of vegetal origin
      underscores the relevance of prevention programs aimed at children younger than 3
      years of age.

PMID- 18345451
TI  - Prevalence of pulmonary hypertension evaluated by Doppler echocardiography in a
      population of adolescent and adult patients with cystic fibrosis.
AB  - OBJECTIVE: To determine the prevalence of pulmonary hypertension (PH) in patients
      with cystic fibrosis (CF), to compare clinical characteristics, radiographic
      scores, pulmonary function, and echocardiographic parameters in patients with and
      without PH, and to correlate echocardiographic findings with clinical
      characteristics, radiographic scores, and pulmonary function. METHODS: This was a
      prospective, cross-sectional study involving clinically stable patients (aged 16
      or older) enrolled in an adult CF program. The patients were submitted to
      clinical evaluation, Doppler echocardiography, pulmonary function tests, and
      chest X-rays. RESULTS: Tricuspid regurgitant jet velocity (TRV) was obtained in
      37 of the 40 patients studied. The prevalence of PH was 49% with a TRV cut-off of
      2.5 m/s (18 patients) and 30% with a TRV cut-off of 2.8 m/s (11 patients).
      Peripheral oxygen saturation (SpO2) at rest, clinical score, forced expiratory
      volume in one second (FEV1), and forced vital capacity (FVC) were significantly
      lower in the group with PH. The TRV was found to correlate significantly with
      SpO2 at rest (p < 0.001), clinical score (p < 0.001), radiographic score (p =
      0.030), FEV1 in liters (p < 0.001) and in % of predicted (p < 0.001), and FCV in
      liters (p = 0.008) and in % of predicted (p = 0.001). The single best predictor
      of TRV was SpO2 at rest (p < 0.001). CONCLUSION: The high prevalence of PH in the
      CF patients studied suggests that PH should be considered in the evaluation and
      follow-up treatment of such patients. The best predictor of PH was SpO2 at rest.

PMID- 18345452
TI  - Smoking in a small city: an ethnographic study to serve as a base for the
      creation of a public health program.
AB  - OBJECTIVE: To outline the prevalence of smoking in the city of Parazinho, Brazil,
      with the objective of generating data on which to base a plan of action for
      smoking control programs in the city. METHODS: A questionnaire was applied to 150
      people (25.6% of whom were smokers) by community health agents during home
      visits. The questionnaire comprised 30 objective and subjective questions to
      collect social and biological information on smokers in urban and rural areas.
      RESULTS: The data were analyzed using descriptive statistics, and the principal
      findings were as follows: the prevalence of smoking was higher among males
      (57.8%); most of the interviewees started smoking at an early age (45% before the
      age of 12); economic conditions constituted a contributing factor (66% of the
      smokers interviewed earned less than the minimum wage); most of the interviewees
      reported difficulty in kicking the habit (44.6% reported living with a smoker,
      and 80% had a friend who smoked); there was a high prevalence of tobacco-related
      diseases (56.6% had respiratory problems); and there was concomitant alcohol use
      in 52% of the smokers. CONCLUSION: This outline can be used in the generation of
      a local program of smoking prevention and control. Such a program is, in fact,
      under development. A team of professionals has received training in a 'minimal,
      intensive approach to the smoker', and a municipal outpatient clinic for the
      treatment of nicotine dependence has been inaugurated.

PMID- 18345453
TI  - Tuberculous uveitis at a referral center in southeastern Brazil.
AB  - OBJECTIVE: To describe the occurrence of tuberculous uveitis (TBU) at a referral
      center in the state of Minas Gerais, Brazil. METHODS: A total of 16 consecutive
      patients (>15 years of age) who underwent diagnostic evaluation of uveitis
      between January of 2001 and July of 2004 at the Minas Gerais State Referral
      Center were selected for study. Demographic and clinical data, as well as data
      related to screening for toxoplasmosis, syphilis, and rheumatologic diseases,
      together with the results of tuberculin skin testing and HIV testing, were
      collected. RESULTS: Of the16 patients evaluated, 11 (69%) were found to have TBU.
      A history of contact with pulmonary tuberculosis was reported by 8 (72%) of the
      11 patients with TBU and by 1 (20%) of the 5 with non-TBU. Although the odds
      ratio for this association was 10.67 (95% CI: 0.59-398.66), the p value was
      borderline significant (p = 0.078). There was no difference between the patients
      with TBU and those with non-TBU in terms of the status of ocular inflammation or
      the tuberculin skin testing results. All of the patients were HIV negative and
      were monitored for two years. CONCLUSION: In this study, a history of contact
      with pulmonary tuberculosis proved to be useful in diagnosing TBU.

PMID- 18345454
TI  - Brazilian examples of programs for the control of asthma.
AB  - The aim of this study was to determine which Brazilian programs demonstrate
      experience in asthma management. Data on and characteristics of those programs
      were obtained by electronic mail. The variables studied were related to the
      program itself, its patients and staff. Descriptive statistics were used in the
      study, which evaluated 17 programs. All programs received public funding,
      produced educational/training materials and had specialized physicians on staff.
      We concluded that the experience accumulated by all the programs can be used as
      one of the pillars of a national program for the control of asthma in Brazil.

PMID- 18345455
TI  - Cystic fibrosis in adults: diagnostic and therapeutic aspects.
AB  - Once considered a childhood disease, cystic fibrosis is now also a disease of
      adults. Increased longevity has resulted in the aging of the cystic fibrosis
      population. The consequent age-related medical problems among adults with cystic
      fibrosis have increased medical care needs. These needs are being met by a
      growing number of non-pediatric pulmonologists and other non-pediatric
      specialists. The objective of this review was to summarize the current knowledge
      about diagnosis and treatment in adult cystic fibrosis. In most cases, the
      diagnosis is suggested by manifestations of chronic sinopulmonary disease and
      exocrine pancreatic insufficiency. The diagnosis is confirmed by a positive sweat
      test result. Adult patients may, however, present pancreatic sufficiency and
      atypical clinical features, sometimes in combination with normal or borderline
      sweat test results. In such cases, identifying cystic fibrosis mutations and
      measuring nasal potential difference can have diagnostic utility. The standard
      therapeutic approach to pulmonary disease includes the use of antibiotics, airway
      clearance, exercise, mucolytics, bronchodilators, oxygen therapy, anti
      inflammatory agents and nutritional support. Appropriate application of these
      therapies results in most cystic fibrosis patients surviving into adulthood with
      an acceptable quality of life.

PMID- 18345456
TI  - A very rare cause of dyspnea with a unique presentation on a computed tomography
      scan of the chest: macrophage activation syndrome.
AB  - Macrophage activation syndrome is a rare and potentially life-threatening
      disease. It occurs due to immune dysregulation manifested as excessive macrophage
      proliferation, typically causing hepatosplenomegaly, pancytopenia and hepatic
      dysfunction. Here, we report an unusual case of macrophage activation syndrome
      presenting as dyspnea, as well as (reported here for the first time) high
      resolution computed tomography findings of an excavated nodule, diffuse ground
      glass opacities and consolidations (mimicking severe pneumonia or alveolar
      hemorrhage). The patient was successfully treated with human immunoglobulin. We
      recommend that macrophage activation syndrome be considered in the differential
      diagnosis of respiratory failure. Rapid diagnosis and treatment are essential to
      achieving favorable outcomes in patients with this syndrome.

PMID- 18345457
TI  - Management of recurrent distal tracheal stenosis using an endoprosthesis: a case
      report.
AB  - The authors report the case of a patient with recurrent distal tracheal stenosis
      after several tracheal resections. A T-Y tracheobronchial stent was inserted for
      the management of distal airway obstruction. The prosthesis was adapted based on
      the specifications obtained through a computed tomography scan of the chest with
      three-dimensional reconstruction.

PMID- 18345458
TI  - Evaluation of a malaria antibody enzyme immunoassay for use in blood screening.
AB  - Transfusion-transmitted malaria is rare, but it may produce severe problem in the
      safety of blood transfusion due to the lack of reliable procedure to evaluate
      donors potentially exposed to malaria. Here, we evaluated a new enzyme-linked
      immunosorbent assay malaria antibody test (ELISA malaria antibody test, DiaMed,
      Switzerland) to detect antibodies to Plasmodium vivax (the indigenous malaria) in
      the blood samples in the Republic of Korea (ROK). Blood samples of four groups
      were obtained and analyzed; 100 samples from P.vivax infected patients, 35 from
      recovery patients, 366 from normal healthy individuals, and 325 from domestic
      travelers of non-endemic areas residents to risky areas of ROK. P.vivax antibody
      levels by ELISA were then compared to the results from microscopic examination
      and polymerase chain reaction (PCR) test. As a result, the ELISA malaria antibody
      test had a clinical sensitivity of 53.0% and a clinical specificity of 94.0% for
      P.vivax. Twenty out of 325 domestic travelers (6.2%) were reactive and 28 cases
      (8.6%) were doubtful. Of the reactive and doubtful cases, only two were confirmed
      as acute malaria by both microscopy and PCR test. Thus we found that the ELISA
      malaria antibody test was insufficiently sensitive for blood screening of P.vivax
      in ROK.

PMID- 18345459
TI  - Environmental risk factors for Cryptosporidium infection in an island from
      Western Venezuela.
AB  - Few investigations have been conducted on risk factors for Cryptosporidium
      infection in communities from developing countries. A study was conducted to
      determine the prevalence and risk factors for cryptosporidiosis in San Carlos
      island, Venezuela. A sample of 515 subjects (mean age +/- SD: 21.4 +/- 17.8
      years) was surveyed. Single fecal specimens were collected and modified Ziehl
      Neelsen carbolfuchsin staining of formalin-ether concentrate stools were examined
      for identification of the parasite. Infections with Cryptosporidium (67 of 515,
      13%) were common. Prevalence of the parasite varied among sectors of the
      community; 34 of 67(50.7%) cases of cryptosporidiosis clustered in two sectors
      with extreme poverty. Variables strongly associated with a higher risk for the
      infection (p < 0.01) were residing in these sectors versus the remainder, living
      in a hut or small residence versus a brick or larger house, using an area of
      backyard rather than a toilet or latrine for defecation, and having contact with
      soil contaminated with human feces. Crowding was also a risk (p < 0.05). Contact
      with human feces contaminated-soil may be an important mode of transmission and
      poverty a predisposing factor for the infection.

PMID- 18345460
TI  - Importance of TNF-alpha in the course of acute infection with Trypanosoma cruzi:
      influence of its inhibition by pentoxifylline treatment.
AB  - Infection of C3H/He mice with the Peruvian strain of Trypanosoma cruzi (Biodeme
      type I, Z2b), a macrophagotropic strain, determined severe parasitism of
      macrophages, necrosis of the spleen, and high host mortality. In the present
      study, pentoxifylline (PTX), an inhibitor of TNF-alpha was investigated on its
      action upon splenic necrosis, parasitemia and host survival. Immunohistochemical
      data suggested the importance of this cytokine in parasite destruction and
      decreasing of parasitemia, although paradoxically contributing to the high
      mortality of infected mice. Necrotic lesions involving several organs, specially
      the heart, in acute Chagas disease, are important aggravating factors, increasing
      cardiac morbidity. Advantage of inhibiting TNF-alpha action was herein
      investigated. Infected mice were divided into two groups: untreated (n = 24), and
      PTX treated mice (n = 25). PTX was administered in two daily doses of 30
      mg/kg/bw, by intraperitoneal route. Normal controls either treated with PTX or
      saline were also included. Histopathology of the spleen and in situ
      immunolabeling of TNF-alpha, using anti-TNF-alpha monoclonal antibody, were
      performed. Necrotic areas were evaluated by morphometry. Mice treated with PTX
      showed a significant decrease of necrotic areas and diminution of TNF-alpha
      expression in spleen tissue, suggesting that PTX treatment could control TNF
      alpha effects, and thus be used as an adjuvant in the treatment of acute Chagas'
      disease.

PMID- 18345461
TI  - A new miracidia hatching device for diagnosing schistosomiasis.
AB  - It is still imperative to develop a parasitological technique highly sensitive
      for diagnosing schistosomiasis in epidemiological and individual surveys. A
      simple and cheap hatching device with a collecting container was manufactured and
      tested under experimental conditions. Twelve Kato-Katz slides were performed as
      golden standard for comparison. Quantitative results can be carried out by
      counting miracidia in a plate and parasite load can be calculated (miracidia/gram
      of feces). Statistically significant values were higher in the hatching test.
      More sensitive results, with statistical significance, were achieved using 1.5 g
      of feces (which corresponds to 36 Kato-Katz slides) than by using the Kato-Katz
      method. Advantages of this technique and its limitations are presented.

PMID- 18345462
TI  - Assessing atopic disease in children two to six years old: reliability of a
      revised questionnaire.
AB  - BACKGROUND: Primary intervention - reducing second hand smoking (SHS), indoor
      dampness, and increased intake of omega-3-fatty acids - for allergic diseases
      such as asthma, rhinoconjunctivitis, and eczema/dermatitis in children was
      started in Trondheim in 2002. To our knowledge, no validated or reliable
      questionnaires for the study age groups were available. AIMS: To test the
      reliability of a revised questionnaire for studying atopic disease in children
      two to six years old in Trondheim. METHODS: Seventy-seven families were invited
      to fill in a questionnaire adapted from the ISAAC protocol which was made
      appropriate for the age group studied. Completed questionnaires and information
      from medical records were compared, and the agreement was analysed by Kappa
      statistics and proportional agreement. RESULTS: Agreement was excellent for
      questions reporting current information such as doctor-diagnosed asthma
      (kappa=0.88), whether or not the child had had an allergy test (kappa=0.82), and
      use of antibiotics (kappa=0.81). The agreement was good for questions concerning
      doctor or hospital treatment for asthma (kappa=0.59), medication for asthma
      (kappa=0.58), symptoms of eczema (kappa=0.56), medication for allergic disease
      (kappa=0.45), and past infections (kappa=0.53). CONCLUSION: Questions on asthma
      diagnosis, allergy testing, and use of antibiotics were reliable. Questions on
      medical treatment for eczema, allergic rhinoconjunctivitis and infections were
      less reliable, representing a potential source of information bias and possible
      misclassification.

PMID- 18345468
TI  - [Framework of palliative care in Germany and development of public health
      targets. Study design and methods].
AB  - To provide adequate end-of-life care is a substantial task of the health care
      system. However, it has been largely disregarded. For public health research,
      important activities include analysing the societal requirements as well as the
      health system-related possibilities and framework. Therefore, a study, funded by
      the German Research Foundation, for the first time (1) examines the viewpoints of
      a wide range of stakeholders that operate on different levels of the German
      health system, and (2) develops broadly based public health targets for
      palliative care in Germany. This article presents the conceptual framework,
      design and methods of the study.

PMID- 18345469
TI  - [Development of national guidelines for depression].
AB  - Depressive disorders rank among the most frequent causes of consultation and
      diseases in health care. Although they are treatable, there is further need to
      optimize diagnostics and therapy, despite sizable progress in recent years. The
      implementation of evidence- and consensus-based guidelines is an appropriate
      measure to improve care for depressive patients. An evidence-based guideline for
      depression is currently being developed for Germany. In order to ensure its
      acceptance and a wide dissemination, this guideline will be adopted in consensus
      by all relevant health care providers in this field. According to this, it is a
      future challenge to anchor guideline-based diagnostics and treatment in routine
      care.

PMID- 18345470
TI  - [Transcultural aspects of depression].
AB  - For many decades it was assumed that depressive disorders are mainly a problem of
      Western societies. However, a World Bank report published in 1993 revealed that
      Major Depression is already the fifth leading contributor to the Global Burden of
      Disease (GBD) among women in developmentally disadvantaged countries. The core
      symptoms of depression are disorders of affect, conduct and somatic complaints.
      In Western societies, the key symptom of depression is regarded to be a disorder
      of affect. However, in other cultural settings, different symptoms may be more
      central for depression. Nowadays mental health specialists have regular contact
      with patients from different cultural backgrounds. In order to achieve optimal
      results in diagnosing and treating mental disorders, it is important to consider
      the cultural background of a patient and her or his explanatory model of the
      disease. Transcultural psychiatry and psychotherapy aims at developing culture
      sensitive concepts for treatment and mental health services and tries to increase
      insight in culture-related psychopathology and epidemiology.

PMID- 18345471
TI  - [Psychotherapy of depression].
AB  - There are now several well evaluated (psychological) interventions available to
      treat depressive disorders. A large number of controlled randomized trials have
      been conducted to establish scientific evidence for treatments' short- and long
      term outcome. If the patient meets the diagnostic criteria for depression, a
      decision has to be made about referral to a psychiatrist or a psychotherapist for
      specialized treatment. Depending on severity of symptomatology (suicidality) as
      well as the range of individual problems, supportive counselling or specific
      psychotherapy is indicated. Specific psychotherapies for depression are in
      particular cognitive behaviour therapy (CBT) and interpersonal psychotherapy
      (IPT), to a less extent short-term psychodynamic psychotherapy (STPP) and client
      centred psychotherapy (CCPT). For these specific psychotherapies, empirical
      evidence is available about short-term (successful symptom reduction) and long
      term (relapse prevention) outcome as monotherapy or in combination with
      antidepressive medication. Based on available outcome studies, 14 up-to-date
      treatment recommendations conclude this presentation.

PMID- 18345472
TI  - [Depression in old age].
AB  - Depression is the most frequent psychiatric disorder in old age. Some patients
      have had depressive episodes or other psychological disorder in an earlier part
      of their life span. Older people show more somatic or cognitive complaints
      compared to younger depressives. Risk factors for depression in old age are
      (incident) physical disorders, sleep disorders or loss of spouse. Depression
      worsens course and prognosis of comorbid somatic disorders. A major consequence
      is the high suicide rate in the elderly. Depression is also a risk factor for
      other disorders like dementia or institutionalisation. The interplay between
      depression and dementia and other organic brain disorders is complex und still
      unresolved. Depression in the elderly is a challenge for our health system.
      Recognition and treatment rates are still too low. Integrative treatment plans
      for depression with comorbid physical disorders or in various settings should be
      developed. With the growing elderly population the available evidence for
      treatment urgently has to be increased. In current practice drug therapies-
      mostly inadequate--dominate. Psychotherapy should be promoted and the number of
      old age psychotherapists increased.

PMID- 18345473
TI  - Fluoride accumulation in soil and vegetation in the vicinity of brick fields.
AB  - Fluoride in the soil and vegetation in the vicinity of brick field in the suburb
      of Lucknow, India was estimated. The water soluble fluoride (1:1) in the surface
      soil ranged from 0.59 ppm to 2.74 ppm where as CaCl(2) extractable fluoride
      ranged from 0.69 ppm to 3.18 ppm. The mean total fluoride concentration in
      surface soil varied from 322 microg g(-1) to 456 microg g(-1). The local
      vegetations grown in the area found to accumulate air borne fluoride from the
      brick field. The fluoride accumulation in the vegetation followed the order
      Mentha arvensis > Spinacea oleracea > Luffa cylindrical.

PMID- 18345474
TI  - Acid volatile sulfides and simultaneously extracted metals in a metal-polluted
      area of Taihu Lake, China.
AB  - There were similar distribution characteristics for acid volatile sulfides (AVS)
      and simultaneously extracted metals (SEM) in surface sediments, and the
      concentrations of AVS and SEM decreased from the deposition area to the center of
      the bay (lake). The ratio of AVS to SEM was <1 in the surface sediments,
      indicating that heavy metals in surface sediments may be bioavailable. The
      concentration of AVS increased with sediment depth, followed by a decrease with
      large variation, while the concentration of SEM remained constant. By comparing
      the concentration of SEM with total metals, it was shown that extracted Cu and Ni
      decreased with sediment depth, indicating increasing association of Cu and Ni
      with sulfides in deeper sediment layers. The lower extracted ratios for Pb and Zn
      compared with sulfidic sediment illustrated that AVS should not have strong
      control on sediment Pb and Zn. The molar ratio of AVS and reactive iron showed
      that heavy metals were dynamic and active in sediments in this lake.

PMID- 18345475
TI  - Temporal decrease of trivalent chromium concentration in a standardized algal
      culture medium: experimental results and implications for toxicity evaluation.
AB  - The fate of two trivalent chromium salts (nitrate and chloride) in ISO algal
      culture medium was followed over 72 h; i.e., the typical duration of algal
      toxicity tests. Fifty percent of the initial Cr spikes was lost from the
      solutions by 24 h, with losses up to 90% after 72 h. Monitoring of the temporal
      variability of Cr(III) concentrations in algal culture media appears necessary to
      better characterize the toxicity of trivalent chromium to algae.

PMID- 18345476
TI  - Environmental inactivation of Cryptosporidium parvum oocysts in waste
      stabilization ponds.
AB  - The survival of Cryptosporidium parvum oocysts in a waste stabilization pond
      system in northwestern Spain and the effects of sunlight and the depth and type
      of pond on oocyst viability were evaluated using an assay based on the exclusion
      or inclusion of two fluorogenic vital dyes, 4',6-diamidino-2-phenylindole (DAPI)
      and propidium iodide (PI). All tested factors had significant effects (P < 0.01)
      over time on C. parvum oocyst viability. Sunlight exposure was the most
      influential factor for oocyst inactivation. A 40% reduction was observed after 4
      days exposure to sunlight conditions compared with dark conditions. The type of
      pond also caused a significant reduction in C. parvum oocyst viability (P <
      0.01). Inactivation rates reflected that the facultative pond was the most
      aggressive environment for oocysts placed both at the surface (presence of
      sunlight) and at the bottom (absence of sunlight) of the pond, followed by the
      maturation pond and the anaerobic pond. The mean inactivation rates of oocysts in
      the ponds ranged from 0.0159 to 0.3025 day(-1).

PMID- 18345477
TI  - Idiopathic avascular necrosis of the capitate bone: a new case report.
AB  - Idiopathic avascular necrosis (AVN) of the capitate bone is an important,
      although rare, cause of spontaneous onset of wrist pain. Most cases involve
      direct or indirect trauma. Only a few reports of idiopathic avascular necrosis
      have been published. We present a case report of a 32-year-old woman who
      presented with a chief complaint of a left wrist pain, swelling and loss of all
      ranges of motions for approximately 1 year. She had no history of prior wrist
      trauma or steroid use. Laboratory testing for systemic disease or infection were
      negative. Diagnosis of avascular necrosis of the capitate has been made via plain
      film radiology, isotope bone scanning, and computed tomography scan. No etiologic
      factor could be identified. Surgical treatment was recommended, given drilling
      and autogenous bone grafting. Histological analysis showed necrotic bone. The
      physical therapy was implemented to restore function. Two months postoperatively,
      she was almost pain free.

PMID- 18345479
TI  - The urokinase receptor and integrins in cancer progression.
AB  - Enhanced levels of expression of urokinase receptor (uPAR) and certain integrins
      have been linked to cancer cell progression. This has classically been attributed
      to matrix degradation via the activation of the urokinase (uPA)/plasmin system
      and modulation of cell motility and survival through integrin engagement. More
      recently, uPAR has been shown to play multiple roles independent of protease
      activity. Specifically, uPAR has been shown to be intimately involved in the
      regulation of cell adhesion, migration and proliferation in part through
      interactions with other membrane partners, including integrins. The goal of this
      review is to summarize recent insights in the function of uPAR/integrin
      interactions, to provide a framework for understanding the importance of these
      interactions in the context of cancer, and to highlight its potential as a target
      for therapeutic intervention.

PMID- 18345478
TI  - The primary headaches: genetics, epigenetics and a behavioural genetic model.
AB  - The primary headaches, migraine with (MA) and without aura (MO) and cluster
      headache, all carry a substantial genetic liability. Familial hemiplegic migraine
      (FHM), an autosomal dominant mendelian disorder classified as a subtype of MA, is
      due to mutations in genes encoding neural channel subunits. MA/MO are considered
      multifactorial genetic disorders, and FHM has been proposed as a model for
      migraine aetiology. However, a review of the genetic studies suggests that the
      FHM genes are not involved in the typical migraines and that FHM should be
      considered as a syndromic migraine rather than a subtype of MA. Adopting the
      concept of syndromic migraine could be useful in understanding migraine
      pathogenesis. We hypothesise that epigenetic mechanisms play an important role in
      headache pathogenesis. A behavioural model is proposed, whereby the primary
      headaches are construed as behaviours, not symptoms, evolutionarily conserved for
      their adaptive value and engendered out of a genetic repertoire by a network of
      pattern generators present in the brain and signalling homeostatic imbalance.
      This behavioural model could be incorporated into migraine genetic research.

PMID- 18345480
TI  - Structures of vesicular stomatitis virus glycoprotein: membrane fusion revisited.
AB  - Glycoprotein G of the vesicular stomatitis virus (VSV) is involved in receptor
      recognition at the host cell surface and then, after endocytosis of the virion,
      triggers membrane fusion via a low pH-induced structural rearrangement. G is an
      atypical fusion protein, as there is a pH-dependent equilibrium between its pre-
      and post-fusion conformations. The atomic structures of these two conformations
      reveal that it is homologous to glycoprotein gB of herpesviruses and that it
      combines features of the previously characterized class I and class II fusion
      proteins. Comparison of the structures of G pre- and postfusion states shows a
      dramatic reorganization of the molecule that is reminiscent of that of
      paramyxovirus fusion protein F. It also allows identification of conserved key
      residues that constitute pH-sensitive molecular switches. Besides the
      similarities with other viral fusion machineries, the fusion properties and
      structures of G also reveal some striking particularities that invite us to
      reconsider a few dogmas concerning fusion proteins.

PMID- 18345481
TI  - Excitation of histamine on neuronal activity of cerebellar fastigial nucleus in
      rat.

PMID- 18345482
TI  - Plasma histamine levels and symptoms in double blind placebo controlled histamine
      provocation.

PMID- 18345483
TI  - Does histamine influence differentiation of trophoblast in preeclampsia?

PMID- 18345484
TI  - The relationship between human beta-defensin 3 (hBD3) expression and mean
      histamine concentration in human placental tissue.

PMID- 18345485
TI  - Increased production of beta-defensin 3 (hBD-3) by human amniotic epithelial
      cells (HAEC) after activation of toll-like receptor 4 in chorioamnionitis.

PMID- 18345486
TI  - Evaluation of ECP release from intact tissue biopsies from patients with nasal
      polyps.

PMID- 18345487
TI  - Expression of histamine H4 receptor in human osteoarthritic synovial tissue.

PMID- 18345488
TI  - Histamine releasing factor (HRF) in pannus of joints affected by rheumatoid
      arthritis.

PMID- 18345489
TI  - Characterization of the effect of histamine on mouse corpus cavernosum.

PMID- 18345490
TI  - Histamine H3 and H4 receptors are expressed on distinct endocrine cell types in
      the rat fundic mucosa.

PMID- 18345491
TI  - Effect of H1 antihistamines in a model of mesenteric ischaemia/reperfusion.

PMID- 18345492
TI  - Endogenous substrates of the semicarbazide-sensitive amine oxidase increased
      nitric oxide production in rat white adipocytes.

PMID- 18345493
TI  - Characterization of human plasma amine oxidase.

PMID- 18345494
TI  - Comparative investigations of the influence of H1-antihistamines on the
      generation of reactive oxygen species by phagocytes.

PMID- 18345495
TI  - Histamine receptor H4R-selective ligands influence the STAT6 Transcription
      Activation Domain (TAD) and the DNA-binding.

PMID- 18345496
TI  - Minimization of potential hERG liability in histamine H3 receptor antagonists.

PMID- 18345497
TI  - Molecular determinants of ligand-directed signaling for the histamine H1
      receptor.

PMID- 18345498
TI  - The roles of histamine H1 receptors on cognition.

PMID- 18345499
TI  - Histamine uptake into human vascular endothelial cells and influence of three
      different antidepressant drugs.

PMID- 18345500
TI  - Central serotonin-induced pressor effect in rats is mediated in part via the
      histaminergic system.

PMID- 18345501
TI  - The synergistic effect of histamine and IL-6 on NGF secretion from cultured
      astrocytes is evoked by histamine stimulation of IL-6 secretion via H1-receptor
      PKC-MAPK signalling pathway.

PMID- 18345502
TI  - Famotidine, a H2 receptor antagonist, decreases the late phase of orthodontic
      tooth movement in rats.

PMID- 18345503
TI  - Cetirizine, a histamine H1 receptor antagonist, decreases the first stage of
      orthodontic tooth movement in rats.

PMID- 18345504
TI  - Confirmation of biological effects of high dilutions. Effects of submolecular
      concentrations of histamine and 1-, 3- and 4-methylhistamines on human basophil
      activation.

PMID- 18345505
TI  - Part III. keyword-based, boolean-logic driven data-mining discloses correlations
      between additional idiopathic conditions, occlusive vascular diseases such as
      tropical endomyocardial fibrosis with unexplained eosinophilia, and 'histamine
      dysmetabolism'.

PMID- 18345506
TI  - Histamine regulates pancreatic carcinoma cell growth through H3 and H4 receptors.

PMID- 18345507
TI  - Pharmacological actions of a new synthetic cyclodepsipeptide, the A83586C
      citropeptin hybrid, on complement C5a and G-Proteins.

PMID- 18345508
TI  - Effect of histamine chloramine on luminol-dependent chemiluminescence of
      granulocytes.

PMID- 18345509
TI  - Substance P-induced cycloxygenase-2 expression in polymorphonuclear cells.

PMID- 18345510
TI  - In vitro inhibition of rat basophilic leukaemia mast cell (RBL-2H3) degranulation
      by novel indane compounds.

PMID- 18345511
TI  - Comparison of the effect of 4-methyl histamine on human and mouse basophil
      activation.

PMID- 18345512
TI  - A comparison of procedures for purifying human basophils to near homogeneity.

PMID- 18345513
TI  - Antagonism between histamine and polyamines in mast cells.

PMID- 18345514
TI  - Mast cell inhibition and reduced ventricular arrhythmias in a swine model of
      acute myocardial infarction upon therapeutic administration of relaxin.

PMID- 18345515
TI  - Intracranial recurrence and distant metastasis of scalp dermatofibrosarcoma
      protuberans.
AB  - Only few cases of scalp dermatofibrosarcoma protuberans with intracranial and
      distant metastasis have been reported. Here we report a case of scalp
      dermatofibrosarcoma protuberans with frequent local recurrence, intracranial
      invasion and with distant lung metastasis during 6 years of treatment. We would
      like to emphasize difficulties in surgical treatment of such invasive and locally
      recurrent tumors of scalp, and necessity to understand new molecular pathogenesis
      of dermatofibrosarcoma protuberans and potential treatment strategy with imatinib
      for patients with surgically untreatable disease. Close surveillance of patients
      with scalp dermatofibrosarcoma is necessary due recurrence nature of tumor.

PMID- 18345516
TI  - Clinical relevance of 1p and 19q deletion for patients with WHO grade 2 and 3
      gliomas.
AB  - PURPOSE: To assess the frequency of chromosomes 1p and 19q deletions in gliomas
      and to correlate 1p deletion with prognosis in patients with grade 2 and grade 3
      gliomas independently of histologic subtype. METHODS: We retrospectively
      evaluated 208 patients with WHO grade 2 and 3 gliomas who had 1p/19q molecular
      studies performed between 2000 and 2004. DNA was extracted from tumor tissue and
      germline material and evaluated by PCR using microsatellite markers for each
      chromosome. RESULTS: There were 113 men and 95 women with a median age at
      diagnosis of 40. Thirty-eight patients had a low-grade astrocytoma (A2), 58 low
      grade oligodendroglioma (O2), 31 low-grade oligoastrocytoma (OA2), 21 anaplastic
      astrocytoma (A3), 37 anaplastic oligodendroglioma (O3), and 23 had an anaplastic
      oligoastrocytoma (OA3). Chromosome 1p analysis was performed in all patients and
      showed deletions in 105 patients (76% of O2, 42% of OA2, 21% of A2, 89% of O3,
      17% of AO3, and 14% of A3). Chromosome 19q studies were performed in 118 patients
      and showed deletions in 46 (56% of O2, 45% of OA2, 27% of A2, 76% of O3, 11% of
      OA3 and 0% of A3). On multivariate analyses, chromosome 1p was a prognostic
      factor for prolonged PFS (HR = 1.75, P = 0.03) and OS (HR = 3.59, P = 0.02) in
      grade 2 gliomas but not for grade 3 (HR = 0.81, P = 0.7 for PFS; HR = 1.31, P =
      0.7 for OS). CONCLUSION: Chromosome 1p deletion is a significant positive
      prognostic marker in diffuse, grade 2 gliomas regardless of histologic subtype.

PMID- 18345517
TI  - Anaplastic glioma after high-dose proton-photon radiation treatment for low-grade
      skull base chondrosarcoma.
AB  - We report the case of a 63-year-old man who developed an anaplastic
      oligoastrocytoma of the brain stem and midbrain 13 years after postoperative high
      dose proton-photon radiation therapy for a recurrent low-grade chondrosarcoma of
      the skull base. To our knowledge, this is the first reported case of an
      anaplastic glioma after proton-photon irradiation.

PMID- 18345518
TI  - Excision of selectable marker gene from transgenic tobacco using the GM-gene
      deletor system regulated by a heat-inducible promoter.
AB  - To excise a selectable marker gene from transgenic plants, a new binary
      expression vector based on the 'genetically modified (GM)-gene-deletor' system
      was constructed. In this vector, the gene coding for FLP site-specific
      recombinase under the control of a heat shock-inducible promoter HSP18.2 from
      Arabidopsis thaliana and isopentenyltransferase gene (ipt), as a selectable
      marker gene under the control of the cauliflower mosaic virus 35S (CaMV 35S)
      promoter, were flanked by two loxP/FRT fusion sequences as recombination sites in
      direct orientation. Histochemical staining for GUS activity showed that, upon
      induction by heat shock, all exogenous DNA, including the selectable marker gene
      ipt, beta-glucuronidase (gusA) gene and the FLP recombinase gene, between two
      loxP/FRT sites was eliminated efficiently from primary transgenic tobacco plants.
      Molecular analysis further confirmed that excision of the marker gene (ipt) was
      heritable and stable. Our approach provides a reliable strategy for auto-excising
      a selectable marker gene from calli, shoots or other tissues of transgenic plants
      after transformation and producing marker-free transgenic plants.

PMID- 18345519
TI  - Multiple myeloma emerging after chemotherapy for non-small-cell lung cancer.
AB  - A 67-year-old man underwent total resection of the left lung because of
      adenocarcinoma, with no evidence of extra-thoracic spread of the cancer. On
      follow-up, metastatic bone disease was documented and chemotherapy (CMT) which
      included cisplatin, docetaxel, vinorelbine, and topotecan was administered. Six
      months after completion of CMT, a rise in total serum protein was noted. Bone
      marrow biopsy revealed the diagnosis of an IgG lambda myeloma. We report a case
      of a man with adenocarcinoma of the lung who presented multiple myeloma after
      completion of chemotherapy.

PMID- 18345520
TI  - A preliminary report on spinal muscular atrophy lymphoblastoid cell lines: are
      they an appropriate tool for drug screening?
AB  - INTRODUCTION: Spinal muscular atrophy (SMA) is a neurodegenerative disease of the
      motor neurons that results in progressive muscle weakness. It is also the leading
      hereditary cause of infant mortality. Homozygous loss of the survival motor
      neuron (SMN1) gene causes SMA, and the number of copies of the SMN2 gene
      modulates the severity of the disease. Increasing the expression of the SMN2 gene
      by pharmacological agents is one of the therapeutic approaches currently being
      implemented. METHODS: In this preliminary study, we investigated the effect of
      phenylbutyrate, a histone deacetylase (HDAC) inhibitor, on SMN2 expression in two
      SMA type III Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines to
      understand the suitability of lymphoblastoid cell lines in drug screening. These
      cell lines are regarded as a good source as they can easily be established from
      the peripheral leucocytes of patients. Quantitative analysis of SMN2 mRNA was
      performed on established cell lines treated with various concentrations of
      phenylbutyrate and for a range of incubation periods using real-time polymerase
      chain reaction. Western blot analysis was used to determine SMN protein levels.
      RESULTS: Real-time polymerase chain reaction and Western blot analysis
      demonstrated that the levels of SMN2 full-length (fl-SMN2) transcripts and
      protein were not increased in phenylbutyrate-treated cell lines compared to non
      treated controls. CONCLUSION: These results suggest that EBV-transformed
      lymphoblastoid cell lines are not suitable for studying the effect of certain
      HDAC inhibitors on SMN2 gene expression.

PMID- 18345521
TI  - Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish
      female patients.
AB  - PURPOSE: To evaluate the results of gonadotropin-releasing hormone agonist
      (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two
      demographically matched groups of normoresponder in-vitro fertilisation or
      intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study.
      METHODS: We randomised 93 patients undergoing IVF/ICSI between May 2005 and
      August 2006. Patients with IVF indications were included except for those with
      polycystic ovary syndrome or azoospermia, women older than 38 years and those
      with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated
      with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant
      cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of
      > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa,
      leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was
      administered when at least three follicles of 18 mm in diameter were observed.
      Oocyte retrieval was scheduled 36 hours following hCG administration and embryos
      were transferred on day 3 after oocyte retrieval. RESULTS: The two groups were
      homogenous for age, infertility duration, basal FSH and serum oestradiol (E2)
      (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa
      group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and
      higher peak E2 levels (P<0.001) were observed. No differences were observed in
      the number of oocytes retrieved (P=0.749), embryos achieved and transferred
      (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no
      statistically significant difference between groups in clinical pregnancy rates,
      cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415,
      respectively). CONCLUSION: GnRHant and GnRHa provide comparable results in
      normoresponder patients, while GnRHant allows a greater flexibility in their
      treatment.

PMID- 18345522
TI  - IABP-Related vascular complications: who is responsible--the patient, the surgeon
      or the sheath? Part I: sheath-related complications.
AB  - INTRODUCTION: An intra-aortic balloon pump (IABP) is frequently used as a
      mechanical support during the treatment of low cardiac output syndrome. The use
      of a sheath during IABP treatment can be associated with ischaemic complications
      in the extremities. The aim of our study was to determine the isolated role of
      sheaths in the development of vascular complications following IABP
      catheterisation. METHODS: We evaluated a total of 81 patients who had received an
      IABP for haemodynamic stability, between January 2003 and October 2007, following
      cardiovascular surgery. To eliminate surgical-related variables, only patients
      with IABPs and size 8.5 or 9 French catheters (inserted by experienced
      cardiovascular surgeons using the percutaneous Seldinger technique) were included
      in the study. To eliminate patient-related variables, patients with a known risk
      factor for either thrombosis, embolus or peripheral arterial disease were
      excluded from the study. RESULTS: The patients were divided into two groups:
      Group 1 (sheathed catheter group; n=42), Group 2 (sheathless catheter group;
      n=39). Ischaemic complications were observed in a total of five patients. Four of
      these patients were from Group 1 and one was from Group 2. CONCLUSION: Sheathed
      catheterisation was found to increase the risk of vascular complications in
      patients who underwent IABP application. Therefore sheathless catheterisation is
      recommended for IABP application.

PMID- 18345523
TI  - [Confusion Assessment Method for the Intensive Care Unit (CAM-ICU): diagnosis of
      postoperative delirium in cardiac surgery].
AB  - OBJECTIVE: Since 2001 the Confusion Assessment Method for the Intensive Care Unit
      (CAM-ICU), a method for the diagnosis of delirium, has been available for the
      Anglo American area which can also be applied to mechanically ventilated
      patients. This study was conducted to answer the following questions: 1. Can a
      German version of the CAM-ICU be applied to patients after cardiac surgery? 2.
      What is the prevalence rate of postoperative delirium after cardiac surgery
      diagnosed by the CAM-ICU? 3. Do patients with and without the diagnosis delirium
      differ in the clinical variables usually associated with this disorder in cardiac
      surgery? METHODS: A total of 194 patients undergoing cardiac surgery served as
      the analysis sample (85.5% of the total group). The CAM-ICU was carried out every
      day for 5 days after the operation. Sociodemographic and clinical variables were
      collected to examine the validity of CAM-ICU. Postoperative complaints were
      assessed by the Anaesthesiological Questionnaire for Patients (ANP). RESULTS:
      Postoperatively, the CAM-ICU could be applied to almost all patients without any
      problems. The prevalence rate of delirium was 28.4% and 85.5% of the delirium
      diagnosed was a hypoactive subtype when diagnosed for the first time. Patients
      with delirium diagnosed by CAM-ICU were older (p<0.001), had a lower educational
      level (p<0.05), longer anaesthesia time and operation time (p<0.05), a longer
      postoperative ICU stay (p<0.001), were mechanically ventilated for a longer time
      postoperatively (p<0.001), more often reintubated (p<0.01) and had higher
      leucocytes postoperatively (p<0.10). More patients with delirium had the lowest
      postoperatively measured oxygen saturation below 95% (p<0.01). CONCLUSION: The
      CAM-ICU is an economic method for the assessment of delirium which can easily be
      learned. It can be applied to patients after cardiac surgery without any
      problems.

PMID- 18345524
TI  - [Challenge prevention. From curative to preventive medicine-strategic and
      operational challenges].
AB  - The potentials of preventive medicine to reduce the costs of illness have been
      inadequately exploited to date. Even if there is still massive dissent regarding
      the legal setup of a prevention law, prevention should play a significantly
      higher role in practice. Clinicians and practitioners could use preventive
      medicine as another differentiating factor in the increasingly competitive
      healthcare field. Prevention as a new strategic business segment allows a
      directed reaction to the demands of the payment system and opens up enormous
      value-added potential at the same time. Those who seize the chance to integrate
      prevention into their medical services portfolio and into the structure and
      processes of their respective hospitals will develop an important competitive
      advantage for the future.

PMID- 18345525
TI  - [Computer-aided surgery of the paranasal sinuses and the anterior skull base].
AB  - Endoscopic or microscopic surgery for chronic rhinosinusitis with or without
      nasal polyps is a routine intervention in daily practice. It is often a delicate
      and difficult minimally invasive intervention in a narrow space, with a tunnel
      view of 4 mm in the case of endoscopy and frequent bleeding in chronically
      inflamed tissue. Therefore, orientation in such a "labyrinth" is often difficult.
      In the case of polyp recurrence or tumors, the normal anatomical landmarks are
      often missing, which renders orientation even more difficult. In such cases,
      computer-aided navigation together with images such as those from computed
      tomography or magnetic resonance imaging can support the surgeon to make the
      operation more accurate and, in some cases, faster. Computer-aided surgery also
      has great potential for education.

PMID- 18345526
TI  - [Unilateral extended medialization thyroplasty. Treatment for total aspiration
      after laser surgery and radiotherapy of laryngeal cancer].
AB  - BACKGROUND: Total aspiration is a rare complication after extended laser surgery
      for laryngeal cancer with adjuvant radiotherapy. PATIENTS AND METHODS: Two
      patients with long-standing total aspiration after laser surgery with
      radiotherapy despite intensified swallowing therapy were treated with an extended
      medialization thyroplasty. RESULTS: Postoperatively, both patients were able to
      swallow food and liquids without aspiration. One patient no longer has a
      gastrostomy tube and has been free from aspiration with normal oral food intake
      for 3 years. The second patient, with a tiny mucosal scar perforation, developed
      an abscess 2 months after surgery and needed revision surgery, with a subsequent
      return of aspiration. DISCUSSION: The second patient's complication stresses the
      significance of an intact endolaryngeal scar because of the well-known prolonged
      healing of mucosa in the irradiated larynx. In our opinion, the potential
      benefits of medialization thyroplasty outweigh the risk of significant
      complications, especially after irradiation.

PMID- 18345527
TI  - [Substitution of thyroid hormones].
AB  - In patients with overt hypothyroidism the substitution with Levothyroxine is
      mandatory, whereas in patients with subclinical hypothyroidism it is dependent on
      further clinical signs and symptoms. The main parameter indicating sufficient
      substitution of Levothyroxine in patients with primary hypothyroidism is TSH,
      whereas in secondary hypothyroidism it is free T(4). At present Levothyroxine is
      the preparation of choice to restore euthyroidism in hypothyroid patients because
      it is assumed that the peripheral conversion from T(4) to T(3) provides the exact
      amount of T(3) needed by every organ. Intestinal absorption of Levothyroxin is
      around 80%, but only in acid environment and is significantly decreased by proton
      pump inhibitors, antacids, atrophic gastritis and Helicobacter pylori infection.
      The usual required dosage of Levothyroxine is 1.5 microg/kg of body weight but is
      increased under these conditions as well as during early childhood and pregnancy,
      and is decreased in older people. The bioavailability of different Levothyroxin
      generics might change between 0.8 and 1.25. Therefore, the thyroid function of
      patients, receiving another brand of Levothyroxine has to be re-checked.

PMID- 18345528
TI  - [Hormone therapy with estrogens and gestagens in peri- and post-menopause].
AB  - Hormone therapy with estrogens (combined with progestin for women who have not
      been hysterectomized) is the most efficacious treatment for climacteric symptoms.
      A few years ago hormone therapy was considered to be an ideal prevention for
      cardio-vascular disease, osteoporosis, dementia and other diseases. Large
      prospective randomized trials have changed this paradigm. Hormone therapy should
      only be used with a clear indication (moderate to severe climacteric symptoms and
      - with limitations - prevention of osteoporosis). The lowest effective dose
      should be used for the shortest possible time.

PMID- 18345529
TI  - [Consequent preventive therapy protects against stroke: EXPRESS study (Early use
      of Existing Preventive Strategies for Stroke)].

PMID- 18345530
TI  - Interventions to reduce medication prescribing errors in a paediatric cardiac
      intensive care unit.
AB  - OBJECTIVE: To identify and reduce medication-prescribing errors by introducing
      systematic physician education and post-cardiac surgery admission prescription
      forms. DESIGN: Errors were defined as: incomplete prescriptions; potential
      adverse drug events (ADEs), i.e. either intercepted or non-intercepted incorrect
      prescriptions not resulting in an ADE; and incorrect prescriptions that resulted
      in ADEs. Two baseline blinded pre-intervention data collection periods of 4 weeks
      and 1 week were followed by implementation of a post-cardiac surgery templated
      physician order and prescription form and systematic physicians' education.
      Twelve post-intervention data collections of 1-week duration were completed over
      a 3-year period and were either blinded or informed with reinforcement of
      physicians' education. SETTING: Tertiary paediatric cardiac intensive care unit.
      RESULTS: A total of 3648 prescriptions were evaluated at baseline (mean +/- SD of
      687+/- 8 per week) and 811 +/- 129 prescriptions during each post-intervention
      period. Total baseline errors of 16.8% decreased to 8.4% after the first blinded
      data collection and to 4.8% at the final data collection (p<0.001). The
      occurrence of incomplete prescriptions fell from 15.3% at baseline to 3.6% at
      final data collection (p<0.001); intercepted potential ADEs fell from 1.3% to
      1.1%; non-intercepted potential ADEs fell from 0.17% to zero; and post-operative
      prescribing errors fell from 44% to 4.6% (p<0.001), with the major reduction seen
      in incomplete prescriptions. CONCLUSION: The incidence of incomplete
      prescriptions significantly improved with education of physicians and use of post
      cardiac surgery templated physician order and prescription forms. There was no
      impact on potential ADEs.

PMID- 18345531
TI  - Thermal desorption characterisation of molecularly imprinted polymers. Part I: A
      novel study using direct-probe GC-MS analysis.
AB  - A novel thermal desorption technique using a direct-probe device (Chromatoprobe)
      attached to a gas chromatograph-mass spectrometer is presented for the thermal
      pretreatment, characterisation and analysis of molecularly imprinted polymers.
      The technique is demonstrated as effective for the removal of volatile materials,
      including template and unreacted monomers, from methacrylic acid-ethylene glycol
      dimethacrylate copolymers imprinted with 2-aminopyridine. Mass spectrometry is a
      powerful technique for polymer bleed characterisation. Thermal desorption studies
      on reloaded template and related compounds are reported as a means of assessing
      polymer morphology, specific binding by imprinted polymers compared with
      reference non-imprinted polymers and selective binding by an imprinted polymer
      for its template. Calibration studies on the thermal desorption technique using
      an internal standard are presented with R(2) > 0.999. The technique provides a
      novel method for assessment of polymer thermal stability, composition and
      morphology.

PMID- 18345533
TI  - Expanding the scope of MS binding assays to low-affinity markers as exemplified
      for mGAT1.
AB  - Following a recently developed concept of MS binding assays based on the
      quantification of a native marker by LC-MS a procedure to study binding of a low
      affinity marker in kinetic, saturation, and competition experiments was
      established. Separation of bound and unbound marker-the most crucial step of the
      assay-could be effectively achieved by filtration in a 96-well-format. MS binding
      assays according to this procedure allowed the reliable characterization of NO
      711 binding to mGAT1 in presence of physiological NaCl concentrations. Comparing
      the results obtained in the present study with those from experiments using 1 mol
      L(-1) NaCl in the incubation milieu reveals remarkable differences with respect
      to the marker's affinity and kinetics and to the investigated test compound's
      potency. [figure: see text]

PMID- 18345534
TI  - CT and MR imaging in atypical teratoid/rhabdoid tumors of the central nervous
      system.
AB  - INTRODUCTION: Atypical teratoid/rhabdoid tumors (ATRT) are rare aggressive
      neoplasms of the CNS affecting predominantly very young children. METHODS: We
      retrospectively reviewed the imaging findings of 9 CT and 32 MR examinations of
      the brain and spine of 33 children. RESULTS: Of the 33 tumors, 11 were located in
      the infratentorial compartment, 16 in the supratentorial compartment, 5 in both
      cranial compartments, and 1 in the lower thoracic spinal cord. The mean age of
      the children with infratentorial or infra- and supratentorial tumors was
      significantly lower than the mean age of the children with purely supratentorial
      tumors. Heterogeneity on imaging, large size and high tumor stages are striking
      features reflecting the aggressive nature of this histopathological entity.
      Although not present in the majority of children, a distinct and unusual pattern
      of a wavy band-like enhancement surrounding a central hypointensity was present
      in 12 of 32 children (38%) in whom contrast medium was used. CONCLUSION: To the
      best of our knowledge this is the largest number of imaging examinations of ATRTs
      so far reported. A rather unusual pattern of contrast enhancement may be typical
      of ATRTs.

PMID- 18345532
TI  - High-performance liquid chromatography-tandem mass spectrometry in the
      identification and determination of phase I and phase II drug metabolites.
AB  - Applications of tandem mass spectrometry (MS/MS) techniques coupled with high
      performance liquid chromatography (HPLC) in the identification and determination
      of phase I and phase II drug metabolites are reviewed with an emphasis on recent
      papers published predominantly within the last 6 years (2002-2007) reporting the
      employment of atmospheric pressure ionization techniques as the most promising
      approach for a sensitive detection, positive identification and quantitation of
      metabolites in complex biological matrices. This review is devoted to in vitro
      and in vivo drug biotransformation in humans and animals. The first step
      preceding an HPLC-MS bioanalysis consists in the choice of suitable sample
      preparation procedures (biomatrix sampling, homogenization, internal standard
      addition, deproteination, centrifugation, extraction). The subsequent step is the
      right optimization of chromatographic conditions providing the required
      separation selectivity, analysis time and also good compatibility with the MS
      detection. This is usually not accessible without the employment of the parent
      drug and synthesized or isolated chemical standards of expected phase I and
      sometimes also phase II metabolites. The incorporation of additional detectors
      (photodiode-array UV, fluorescence, polarimetric and others) between the HPLC and
      MS instruments can result in valuable analytical information supplementing MS
      results. The relation among the structural changes caused by metabolic reactions
      and corresponding shifts in the retention behavior in reversed-phase systems is
      discussed as supporting information for identification of the metabolite. The
      first and basic step in the interpretation of mass spectra is always the
      molecular weight (MW) determination based on the presence of protonated molecules
      [M+H](+) and sometimes adducts with ammonium or alkali-metal ions, observed in
      the positive-ion full-scan mass spectra. The MW determination can be confirmed by
      the [M-H](-) ion for metabolites providing a signal in negative-ion mass spectra.
      MS/MS is a worthy tool for further structural characterization because of the
      occurrence of characteristic fragment ions, either MS( n ) analysis for studying
      the fragmentation patterns using trap-based analyzers or high mass accuracy
      measurements for elemental composition determination using time of flight based
      or Fourier transform mass analyzers. The correlation between typical functional
      groups found in phase I and phase II drug metabolites and corresponding neutral
      losses is generalized and illustrated for selected examples. The choice of a
      suitable ionization technique and polarity mode in relation to the metabolite
      structure is discussed as well.

PMID- 18345535
TI  - Partial tear of the quadriceps tendon in a child.
AB  - We present a case of partial rupture of the quadriceps tendon in an 8-year-old
      girl. This is one of the youngest patients reported with a quadriceps tendon
      rupture, an entity seen predominantly in middle-aged people. The strength of the
      muscle tendon unit in a child makes tendon injuries extremely unusual as compared
      to apophyseal avulsions. The MR imaging findings of this unusual pediatric injury
      are illustrated.

PMID- 18345536
TI  - Catheters, wires, tubes and drains on postoperative radiographs of pediatric
      cardiac patients: the whys and wherefores.
AB  - Surgical treatment of congenital heart disease has advanced dramatically since
      the first intracardiac repairs in the mid-20th century. Previously inoperable
      lesions have become the focus of routine surgery and patients are managed
      successfully in intensive care units around the world. As a result, increasing
      numbers of postoperative images are processed by departments of radiology in
      children's hospitals. It is important that the radiologist accurately documents
      and describes the catheters, wires, tubes and drains that are present on the
      chest radiograph. This article reviews the reasons for the placement and
      positioning of perioperative equipment in children who have surgical repair of
      atrial septal defect, ventricular septal defect or transposition of the great
      arteries. Also included are a brief synopsis of each cardiac anomaly, the
      surgical procedure for its correction, and an in-depth discussion of the
      postoperative chest radiograph including illustrations of catheters, wires, tubes
      and drains.

PMID- 18345537
TI  - Fast-recovery fast spin-echo T2-weighted MR imaging: a free-breathing alternative
      to fast spin-echo in the pediatric abdomen.
AB  - In the mid 1990s, the fast spin-echo (FSE) and turbo spin-echo (TSE) T2-weighted
      (T2-W) sequences became available and are now widely accepted alternatives to
      conventional spin-echo sequences since they result in reduced acquisition times
      while maintaining tissue contrast. Since that time, there has been continued
      development of new sequences to further decrease acquisition times, minimize
      artifacts, and preserve lesion detection. The purpose of this pictorial essay is
      to qualitatively illustrate the newly available fast recovery (FR) FSE T2-W MR
      images of the abdomen compared with the images acquired using the routine FSE T2
      W sequence in non-breath-hold studies in children.

PMID- 18345538
TI  - [Obstructive sleep apnea in patients with Parkinson's disease--report of two
      cases and review].
AB  - BACKGROUND: The use of continuous positive airway pressure (CPAP) is well
      established in treatment of moderate and severe obstructive sleep apnea syndrome
      (OSAS). The judgement of clinical symptoms like daytime sleepiness and
      hypersomnolence with loss in concentration is complicated in patients with
      diagnosis of Morbus Parkinson (MP) because the disease itself and pharmacologic
      therapy may mimic clinical features of OSAS. PATIENTS AND METHODS: Diagnostic
      pathways and differential diagnostic considerations are demonstrated in two case
      reports of patients with MP and OSAS. The cases are discussed within the
      framework of literature concerning sleep disturbances and MP. RESULTS: In both
      cases respiration could be treated effectively by continuous positive airway
      pressure (CPAP). Patients clearly responded to therapy and regained more daytime
      activity. The medication for MP was satisfactory. CONCLUSIONS: The evaluation and
      treatment of daytime sleepiness in patients with MP and obstructive sleep apnea
      need an interdisciplinary framework with a practitioner, a neurologist, and a
      sleep expert. Associated symptoms as increased nycturia, hypokinesia, restless
      leg-symptoms, and depression as well as the effects of medication may mimic
      details of concomitant sleep apnea. Therefore, sleep diagnostic evaluation is
      recommended to rule out sleep apnea as a frequent cause for hypersomnolence.

PMID- 18345539
TI  - [Uncommon case of paraganglioma syndrome in combination with malignant
      paraganglioma].
AB  - BACKGROUND: Combination of paraganglioma syndrome and malignant paraganglioma is
      an uncommon disease worldwide. PATIENT: We report the case of a 69-year old man
      with a jugular-tympanal paraganglioma, who underwent surgery. Histopathological
      examination revealed a malignant paraganglioma. An other contralateral carotid
      body and a tumor in the thyroid gland had been discovered during staging. The
      molecular results confirmed the existence of a paraganglioma syndrome.
      DISCUSSION: A malignant paraganglioma based on a hereditary paraganglioma
      syndrome is a rare described case in literature. On the background of the
      literature we discuss the pathology, pathogenesis, diagnostic and therapy of this
      disease.

PMID- 18345540
TI  - Pseudoparoxysms.

PMID- 18345541
TI  - Mimicking acute coronary syndrome.

PMID- 18345542
TI  - Pseudoventricular tachycardia.

PMID- 18345543
TI  - Elucidating the role of chest wall irradiation in 'intermediate-risk' breast
      cancer: the MRC/EORTC SUPREMO trial.

PMID- 18345544
TI  - Cloned beef hash.

PMID- 18345545
TI  - A phase I/II study to evaluate the toxicity and efficacy of accelerated
      fractionation radiotherapy for the palliation of dysphagia from carcinoma of the
      oesophagus.
AB  - AIMS: We hypothesised that accelerated fractionated radiotherapy may provide a
      good palliative approach for dysphagia relief in patients with incurable
      oesophageal cancer, significantly reducing the overall duration of treatment,
      while providing symptom response with an acceptable toxicity profile. A phase
      I/II accelerated fractionation study was conducted to evaluate the efficacy and
      toxicity of this approach. MATERIALS AND METHODS: Patients with incurable
      oesophageal cancer, symptomatic with dysphagia, Eastern Cooperative Oncology
      Group performance status<or=3, without fistula or oesophageal stent in situ, were
      eligible. Treatment consisted of 40 Gy in 20 fractions, twice a day (2 Gy per
      fraction, >or=6 h apart), 5 days a week, over 2 weeks. RESULTS: Of the 39
      evaluable patients, the dysphagia response rate was 69% (27/39) with a median
      response duration of 5.5 months. The median time to response was 4 weeks. Twenty
      eight per cent (11/39) of patients had transient worsening in their dysphagia
      scores. Acute toxicity (weeks 1-8) occurred in 41% (16/39) of patients. An
      improvement in global quality of life by week 8 was seen in 42% of patients.
      There were no late neurological sequelae. The median overall survival was 8
      (range 1.7-58+) months. CONCLUSION: The ideal palliative regimen should be
      relatively short, with minimal toxicity, while offering a favourable response
      profile. Accelerated fractionation fulfils these criteria and is a suitable
      treatment alternative for the palliation of dysphagia, especially if the goal is
      to deliver a higher total biological dose within a shorter (2 week) period of
      time.

PMID- 18345546
TI  - All tanked up.

PMID- 18345547
TI  - Seymour Benzer  (1921-2007).

PMID- 18345548
TI  - Pharmaceuticals and medical devices: medical devices. Year end issue brief.

PMID- 18345549
TI  - Enhanced in vitro activation of immunocompetent cells in healthy individuals
      being subcutaneously 'vaccinated' with placebo (physiological saline).
AB  - The effect of subcutaneous injection of physiological saline (given as 'placebo'
      in a randomized double-blinded placebo-controlled study) on immunocompetent cells
      from healthy individuals was analyzed. In two studies in 1998/1999 and 2002, 16
      and 13 healthy individuals, respectively, were injected subcutaneously with 1 ml
      physiological saline twice a week for up to 12 weeks. Lymphocytes were isolated
      before and during exposure and incubated with recall antigens (purified protein
      derivative [PPD], tetanus toxoid [TT], bacillus Calmette-Guerin [BCG]). The
      production of T-helper type 1-, type 2-, and macrophage/monocyte-related
      cytokines was analyzed by ELISA. There was a significant increase of the recall
      antigen-induced production of IFNgamma, IL-5, IL-13, TNFalpha, and GM-CSF in both
      groups during the observation period. Subcutaneous injection of placebo,
      therefore, enhances immunoreactivity. Psychological aspects, activation of the
      autonomous nerve system or local activation of mast cells or dendritic cells may
      be responsible for this phenomenon.

PMID- 18345550
TI  - A national conference to determine research priorities in pediatric solid organ
      transplantation.
AB  - The need for evidence-based practice guidelines requires high quality, carefully
      controlled clinical research trials. This multidisciplinary conference attempted
      to: identify urgent clinical and research issues, identify obstacles to
      performing clinical trials, develop concepts for organ-specific and all-organ
      research and generate a report that would serve as a blueprint for future
      research initiatives. A few themes became evident. First, young children present
      a unique immunologic environment which may lead to tolerance, therefore,
      including young children in immunosuppression withdrawal and tolerance trials may
      increase the potential benefits of these studies. Second, adolescence poses
      significant barriers to successful transplantation. Non-adherence may be
      insufficient to explain poorer outcomes. More studies focused on identification
      and prevention of non-adherence, and the potential effects of puberty are
      required. Third, the relatively naive immune system of the child presents a
      unique opportunity to study primary infections and alloimmune responses. Finally,
      relatively small numbers of transplants performed in pediatric centers mandate
      multicenter collaboration. Investment in registries, tissue and DNA repositories
      will enhance productivity. The past decade has proven that outcomes after
      pediatric transplantation can be comparable to adults. The pediatric community
      now has the opportunity to design and complete studies that enhance outcomes for
      all transplant recipients.

PMID- 18345551
TI  - Boosting natural capital.

PMID- 18345552
TI  - Jeffrey C. Hall.

PMID- 18345553
TI  - Palm surprise.

PMID- 18345554
TI  - Pharmaceuticals and medical devices: business practices. End-of-year issue brief.

PMID- 18345555
TI  - Pharmaceuticals and medical devices: cost savings. End-of-year issue brief.

PMID- 18345556
TI  - Retraction notice to "Novel synthetic approach to 1alpha, 25-dihydroxyvitamin D3
      and analogues" [J. Steroid Biochem. Mol. Biol 103 (2007) 231-234].

PMID- 18345557
TI  - Pharmaceuticals and medical devices: FDA oversight. End-of-year issue brief.

PMID- 18345558
TI  - Pharmaceuticals and medical devices: Medicare Part D. End-of-year issue brief.

PMID- 18345559
TI  - Pharmaceuticals and medical devices: State Pharmaceutical Assistance Programs
      (SPAPs). End-of-year issue brief.

PMID- 18345560
TI  - Long-term care: home- and community-based services. End-of-year issue brief.

PMID- 18345561
TI  - Long-term care: facility quality and safety. End-of-year issue brief.

PMID- 18345562
TI  - Long-term care: end-of-life issues. End-of-year issue brief.

PMID- 18345563
TI  - Long-term care: funding and insurance. End-of-year issue brief.

PMID- 18345564
TI  - Access to health insurance. Year end issue brief.

PMID- 18345565
TI  - Quality of health care.

PMID- 18345566
TI  - Health facilities.

PMID- 18345567
TI  - Health care workforce.

PMID- 18345568
TI  - Health care information technology.

PMID- 18345569
TI  - Medical errors and patient safety.

PMID- 18345570
TI  - Medical malpractice and tort reform.

PMID- 18345571
TI  - Managed care. Year end issue brief.

PMID- 18345572
TI  - Mandated benefits. Year end issue brief.

PMID- 18345573
TI  - Medicaid services. Year end issue brief.

PMID- 18345574
TI  - Medicaid provider tax. Year end issue brief.

PMID- 18345575
TI  - Medicaid copayments. Year end issue brief.

PMID- 18345576
TI  - Medicaid eligibility.

PMID- 18345577
TI  - Medicaid reimbursement.

PMID- 18345578
TI  - Medicaid waivers.

PMID- 18345579
TI  - Federal Medicaid policy. Year end issue brief.

PMID- 18345580
TI  - Medicaid restructuring. Year end issue brief.

PMID- 18345581
TI  - [Informatics in medicine and health care. Second medical informatics congress in
      Yugoslavia organized by the medical informatics section of the Serbian Medical
      Society. 14-16 October 1995 in Novi Sad].

PMID- 18345582
TI  - [Specific aspects of pharmacotherapy in childhood. 4th Pharmacotherapy symposium
      organized by the Pharmacotherapeutic and Pediatric Section of the Serbian Medical
      Society. 24 June 1995].

PMID- 18345586
TI  - [Treatment approaches to rectus sheath hematoma].

PMID- 18345587
TI  - [Efficiency of coenzyme Q(10) for experimental spinal cord injuries].

PMID- 18345588
TI  - [Can dexpanthenol prevent peritoneal adhesion formation? An experimental study].

PMID- 18345589
TI  - [The Turkish Journal of Trauma and Emergency Surgery].

PMID- 18345590
TI  - 'Never mind the quality, feel the width': the nonsense of 'quality',
      'excellence', and 'audit' in education, health and research.
AB  - The worlds of health care and education have been colonised by 'The Audit
      Society' and managerialism. Under the benign guise of 'improving quality' and
      'ensuring value for money' a darker, more Orwellian purpose operates. Academics
      had to be transformed into a workforce of 'docile bodies', willing to scrutinise
      and survey themselves and their 'performance' as outcome deliverers and disciples
      of the new 'Qualispeak'. This paper critiques the current obsession with audit
      and performativity, the constant and often pointless 'change' is that held to be
      so self-evidently 'a good thing' and the linguistic wasteland that so often
      passes for discussion or policy in the Brave New Worlds of health and education.

PMID- 18345591
TI  - Microplate assay for detection of bacterial contamination in tissue culture
      media.
AB  - In the present study, a rapid and simple colorimetric technique has been
      described to determine the presence of bacteria in tissue culture medium used in
      animal cell culture. The microplate assay is based on utilization of MTT [3(4,5
      dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] by bacteria resulting in
      formation of formazan crystals which can be measured colorimetrically.
      Contaminated medium, a standard gram-negative and gram-positive bacteria produce
      formazan from MTT which is related to the bacterial load. The assay has utility
      in screening tissue culture reagents to detect the presence of bacteria.

PMID- 18345592
TI  - Estimation of the number of amino acid substitutions per site when the
      substitution rate varies among sites.
AB  - A general model for estimating the number of amino acid substitutions per site
      (d) from the fraction of identical residues between two sequences (q) is
      proposed. The well-known Poisson-correction formula q = e (-d) corresponds to a
      site-independent and amino-acid-independent substitution rate. Equation q = (1 -
      e(-2d)/2d, derived for the case of substitution rates that are site-independent,
      but vary among amino acids, approximates closely the empirical method, suggested
      by Dayhoff et al. (1978). Equation q = 1/(1 + d) describes the case of
      substitution rates that are amino acid-independent but vary among sites. Lastly,
      equation q = [ln(1 + 2d)]/2d accounts for the general case where substitution
      rates can differ for both amino acids and sites.

PMID- 18345593
TI  - Iraq redux.

PMID- 18345594
TI  - The impact of gender and age matching for long-term graft survival in living
      donor renal transplantation.

PMID- 18345595
TI  - The demonic TIA: a warning of impending stroke.

PMID- 18345596
TI  - Phosphinoarsonium and diarsonium cations from chloride-abstraction-induced
      pnictogen coupling.
AB  - The first salts of phosphinoarsonium, diarsonium, and phosphinodiarsonium ions
      are obtained from reaction mixtures of a chlorophosphine, a tertiary arsine, and
      a chloride-abstracting agent. The versatile synthetic approach has implications
      in the development of a wide variety of interpnictogen compounds.

PMID- 18345597
TI  - Ni[(EPiPr2)2N]2 complexes: stereoisomers (E = Se) and square-planar coordination
      (E = Te).
AB  - The reaction of ((i)Pr 2PE) 2NM.TMEDA (M = Li, E = Se; M = Na, E = Te) with NiBr
      2.DME in THF affords Ni[(SeP (i)Pr 2) 2N] 2 as either square-planar (green) or
      tetrahedral (red) stereoisomers, depending on the recrystallization solvent; the
      Te analogue is obtained as the square-planar complex Ni[(TeP (i)Pr 2) 2N] 2.

PMID- 18345598
TI  - Synthesis, structure, and optical properties of the quaternary seleno-gallates
      NaLnGa4Se8 (Ln = La, Ce, Nd) and their comparison with the isostructural thio
      gallates.
AB  - Three new quaternary seleno-gallates containing rare-earth metals and sodium
      cations, have been synthesized by a solid-state route in evacuated quartz
      ampoules: Na LnGa 4Se 8 ( Ln = La( I), Ce ( II) and Nd ( III)). The synthesis
      involved the stoichiometric combination of sodium polyselenides, rare-earth
      metal, Ga 2Se 3, and Se or elemental Ga in place of Ga 2Se 3. Single-crystal
      structure analysis indicated that the compounds are isostructural to the thio
      analogue, NaNdGa 4S 8. The structures of I- III are described in terms of layers
      of GaSe 4 tetrahedra joined by corner- and edge-sharing; the alkali-metal cations
      and the trivalent rare-earth metal cations occupy square antiprismatic sites
      between the layers. The optical properties of the compounds have been
      investigated and compared with the isostructural thio-gallate. The band gap of I
      was located around 2.65 eV. The band gaps of II and III were 2.66 and 2.73 eV,
      respectively, considerably narrower than their thio-analogues ( approximately 3.4
      eV). The contraction of the band gap was attributed to the shift of the valence
      band to higher energy due to the involvement of higher energy (4p) Se orbitals.
      The 4f --> 5d gap of II is found to be located around 2.32 eV, which is 0.26 eV
      narrower than the thio-analogue is due to a greater dispersion of the Ln-(5d)
      band caused by more covalent Ce-Se bonds as well as rising of the f level energy.

PMID- 18345599
TI  - Homoleptic 2-mercapto benzothiazolate uranium and lanthanide complexes.
AB  - Treatment of [Ln(BH 4) 3(THF) 3] (Ln = Ce, Nd) with 3 and 4 mol equiv of KSBT in
      tetrahydrofuran (THF) led to the formation of [Ln(SBT) 3(THF)] and [K(THF)Ln(SBT)
      4], respectively. The uranium(IV) compound [U(SBT) 4(THF) 2] was obtained from
      U(BH 4) 4 and was reversibly reduced by sodium amalgam into the corresponding
      anionic uranium(III) complex. The crystal structures of [Ln(SBT) 3(THF) 2] (Ln =
      Ce, Nd), [K(15-crown-5) 2][Nd(SBT) 4], [U(SBT) 4(THF)], and [K(15-crown-5)
      2][U(SBT) 4(py)] show the bidentate coordination mode and the thionate character
      of the SBT ligand.

PMID- 18345600
TI  - Extending the coordination chemistry of 1,3,5-triaza-7-phosphaadamantane (PTA) to
      cobalt centers: first examples of co-PTA complexes and of a metal complex with
      the PTA oxide ligand.
AB  - Water-soluble Co (III) and Co (II) complexes with P- or N-coordinated PTA or PTA
      oxide ligands, respectively, have been prepared and fully characterized,
      constituting the first examples of cobalt compounds bearing PTA or any ligand
      with a cage-like PTA core, the latter complex providing also the first PTA oxide
      coordination to a metal center.

PMID- 18345601
TI  - Arylthiolate coordination and reactivity at pseudotetrahedral nickel(II) centers:
      modulation by noncovalent interactions.
AB  - Five new pseudotetrahedral nickel(II) arylthiolate complexes Tp (R,Me)Ni-SR' [(Tp
      (R,Me)) (-) = 2,2,2-kappa (3)-hydridotris(3-R,5-methylpyrazolyl)borate; R = Me,
      R' = C 6H 5 (Ph), 2,4,6-C 6H 2(CH 3) 3 (Mes); R = Ph, R' = C 6H 5 (Ph), 2,4,6-C
      6H 2(CH 3) 3 (Mes), and 2,6-C 6H 3(CH 3) 2 (Xyl)] were prepared by metathesis
      reactions of known chloride complexes with sodium arylthiolate salts in THF. The
      new products were fully characterized. The effect of increasing bulk of
      substituents at the proximal 3-pyrazolyl and ortho-thiolate positions represented
      in this series was evident in spectroscopic studies (UV-vis-NIR, (1)H NMR) of the
      product complexes. Increased steric contact induced red-shifting of nickel
      thiolate ligand to metal charge transfer (LMCT) bands and enhanced contact shifts
      of arylthiolate protons with the paramagnetic ( S = 1) nickel(II) ion. These
      spectroscopic effects arise from structural distortion of the nickel(II)-thiolate
      bond revealed by X-ray crystal structure determinations of the structural
      extremes of the series, Tp (Me,Me)Ni-SPh and Tp (Ph,Me)Ni-SXyl. The distortion
      consists of a significantly increased tilting of the Ni-S bond from an ideal
      trigonal axis and increased linearity of the Ni-S-R angle that alters covalency
      of the Ni-S coordinate bond. Reactivity of the nickel-thiolate linkage toward
      electrophilic alkylation with MeI is also significantly affected, showing
      enhanced rates according to two distinct competing mechanisms, direct bimolecular
      alkylation of intact complex and rate-limiting unimolecular dissociation of free
      thiolate. Possible biochemical relevance of these observations to tetrahedral
      nickel(II) centers in metalloenzymes is considered.

PMID- 18345602
TI  - X-ray crystal structures, electron paramagnetic resonance, and magnetic studies
      on strongly antiferromagnetically coupled mixed mu-hydroxide-mu-N(1),N(2)
      triazole-bridged one dimensional linear chain copper(II) complexes.
AB  - Four new metal-organic polymeric complexes, {[Cu(mu-OH)(mu-ClPhtrz)][(H 2O)(BF
      4)]} n ( 1), {[Cu(mu-OH)(mu-BrPhtrz)][(H 2O)(BF 4)]} n ( 2), {[Cu(mu-OH)(mu
      ClPhtrz)(H 2O)](NO 3)} n ( 3), and {[Cu(mu-OH)(mu-BrPhtrz)(H 2O)](NO 3)} n ( 4)
      (ClPhtrz = N-[( E)-(4-chlorophenyl)methylidene]-4 H-1,2,4-triazol-4-amine;
      BrPhtrz = N-[( E)-(4-bromophenyl)methylidene]-4 H-1,2,4-triazol-4-amine), were
      synthesized in a reaction of substituted 1,2,4-triazole and various copper(II)
      salts in water/acetonitrile solutions. The structures of 1- 4 were characterized
      by single-crystal X-ray diffraction analysis. The Cu(II) ions are linked both by
      single N (1), N (2)-1,2,4-triazole and hydroxide bridges yielding one dimensional
      (1D) linear chain polymers. The tetragonally distorted octahedral geometry of
      copper atoms is completed alternately by two water and two BF 4 (-) anion
      molecules in 1 and 2 but solely by two water molecules in 3 and 4. Magnetic
      properties of all complexes were studied by variable temperature magnetic
      susceptibility measurements. The Cu(II) ions are strongly antiferromagnetically
      coupled with J = -419(1) cm (-1) ( 1), -412(2) cm (-1) ( 2), -391(3) cm (-1) (
      3), and -608(2) cm (-1) ( 4) (based on the Hamiltonian H = - J[ summation
      operator S i . S i+ 1]). The nature and the magnitude of the antiferromagnetic
      exchange were discussed on the basis of complementarity/countercomplementarity of
      the two competing bridges.

PMID- 18345603
TI  - Synthesis, NMR and vibrational spectroscopic characterization, and computational
      study of the cis-IO2F3 2- anion.
AB  - The N(CH3)4(+) salt of the cis-IO2F3(2-) anion was synthesized from [N(CH
      3)4][IO2F2] and excess [N(CH3)4][F] in CH3CN solvent. The [N(CH3)4] 2[IO2F3] salt
      was characterized by Raman, infrared, and (19)F solid-state MAS NMR spectroscopy.
      Geometry optimization and calculation of the vibrational frequencies at the DFT
      level of theory corroborated the experimental finding that the IO2F3(2-) anion
      exists as a single isomer with a cis-dioxo and mer-trifluoro arrangement. The
      fluorine atom in IO2F3(2-) that is trans to one of the oxygen atoms is weakly
      bound with a calculated bond length of 228.1 pm. The IO2F3(2-) anion is only the
      second example of an AEO 2F 3 species after XeO2F3(-).

PMID- 18345604
TI  - An 86Y-labeled mirror-image oligonucleotide: influence of Y-DOTA isomers on the
      biodistribution in rats.
AB  - A mirror-image oligonucleotide (L-RNA) was radiolabeled with the positron
      emitting radionuclide (86)Y (t(1/2) = 14.7 h) via the bifunctional chelator
      approach. DOTA-modification of the L-RNA (sequence: 5'-aminohexyl UGA CUG ACU GAC
      3'; MW 3975) was performed using (S)-p-SCN-Bn-DOTA. (86)Y radiolabeling of the
      DOTA-L-RNA produced more than one species as evidenced by HPLC radiometric
      detection. For the identification of the (86)Y-labeled L-RNA, the structural
      analogue nonradioactive precursor [Y((S)-p-NH2-Bn-DOTA)](-) was synthesized. Two
      coordination isomers were separated via HPLC adopting the square antiprismatic
      (SAP) and the twisted square antiprismatic (TSAP) geometry, respectively. Their
      stereochemical configuration in the solution state was assessed by NMR and
      circular dichroism spectroscopy. Both [Y((S)-p-NH2-Bn-DOTA)](-) isomers were
      converted into isothiocyanate derivatives [Y((S)-p-SCN-Bn-DOTA)](-) and
      conjugated to the L-RNA. The identity of the [(86)Y-DOTA]-L-RNA species was
      finally established by comparison of the radiometric ((86)Y) and UV-visible
      chromatographic profiles. Biodistribution studies in Wistar rats showed minor
      changes in the biodistribution profile of the [(86)Y((S)-p-NH2-Bn-DOTA)](-)
      complex isomers, while no significant differences were observed for the [(86)Y
      DOTA]-L-RNA isomers. High renal excretions were found for the [(86)Y((S)-p-NH 2
      Bn-DOTA)](-) complex isomers as well as for the L-RNA isomers.

PMID- 18345606
TI  - Identification of breast cancer peptide epitopes presented by HLA-A*0201.
AB  - Cellular immune mechanisms detect and destroy cancerous and infected cells via
      the human leukocyte antigen (HLA) class I molecules that present peptides of
      intracellular origin on the surface of all nucleated cells. The identification of
      novel, tumor-specific epitopes is a critical step in the development of
      immunotherapeutics for breast cancer. To directly identify peptide epitopes
      unique to cancerous cells, secreted human class I HLA molecules (sHLA) were
      constructed by deletion of the transmembrane and cytoplasmic domain of HLA
      A*0201. The resulting sHLA-A*0201 was transferred and expressed in breast cancer
      cell lines MCF-7, MDA-MB-231, and BT-20 as well as in the immortal,
      nontumorigenic cell line MCF10A. Stable transfectants were seeded into
      bioreactors for production of > 25 mg of sHLA-A*0201. Peptides eluted from
      affinity purified sHLA were analyzed by mass spectroscopy. Comparative analysis
      of HLA-A*0201 peptides revealed 5 previously uncharacterized epitopes uniquely
      presented on breast cancer cells. These peptides were derived from intracellular
      proteins with either well-defined or putative roles in breast cancer development
      and progression: Cyclin Dependent Kinase 2 (Cdk2), Ornithine Decarboxylase
      (ODC1), Kinetochore Associated 2 (KNTC2 or HEC1), Macrophage Migration Inhibitory
      Factor (MIF), and Exosome Component 6 (EXOSC6). Cellular recognition of the MIF,
      KNTC2, EXOSC6, and Cdk2 peptides by circulating CD8+ cells was demonstrated by
      tetramer staining and IFN-gamma ELISPOT. The identification and characterization
      of peptides unique to the class I of breast cancer cells provide putative targets
      for the development of immune diagnostic tools and therapeutics.

PMID- 18345607
TI  - Design and synthesis of 4-substituted indolo[3,2-e][1,2,3]triazolo[1,5
      a]pyrimidine derivatives with antitumor activity.
AB  - New derivatives of the indolo[3,2- e][1,2,3]triazolo[1,5- a]pyrimidine system,
      substituted in the 4 position, were designed as novel antitumor agents because of
      their theoretical capability to form stable complexes with DNA fragments. The
      calculated free energies of binding were found in the range -12.76 --> -39.68
      Kcal/mol. The docking studies revealed a common binding mode with the chromophore
      intercalated between GC base pairs, whereas the side chain lies along the minor
      groove. Compounds, selected on the basis of the docking studies and suitably
      synthesized, showed antiproliferative activity against each type of tumor cell
      line investigated, generally in the low micromolar range. The more active
      derivatives were shown to be 1eJ and 1eL, endowed with significant
      antiproliferative activity against the renal and CNS subpanels, respectively. A
      mechanism of action closely related to the DNA-interacting drugs can be supposed,
      although, alternative mechanisms, similar to those of the anthracyclines, can
      also operate.

PMID- 18345608
TI  - Constrained analogues of procaine as novel small molecule inhibitors of DNA
      methyltransferase-1.
AB  - Constrained analogues of procaine were synthesized, and their inhibiting activity
      against DNMT1 was tested. Among them, the most potent compound, derivative 3b,
      was also able to induce a recognizable demethylation of chromosomal satellite
      repeats in HL60 human myeloid leukemia cells and thus represents a lead compound
      for the development of a novel class of non-nucleoside DNMT1 inhibitors.

PMID- 18345609
TI  - Identification of 4-(4-aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as
      selective inhibitors of protein kinase B through fragment elaboration.
AB  - Fragment-based screening identified 7-azaindole as a protein kinase B inhibitor
      scaffold. Fragment elaboration using iterative crystallography of inhibitor-PKA
      PKB chimera complexes efficiently guided improvements in the potency and
      selectivity of the compounds, resulting in the identification of nanomolar 6
      (piperidin-1-yl)purine, 4-(piperidin-1-yl)-7-azaindole, and 4-(piperidin-1
      yl)pyrrolo[2,3- d]pyrimidine inhibitors of PKBbeta with antiproliferative
      activity and showing pathway inhibition in cells. A divergence in the binding
      mode was seen between 4-aminomethylpiperidine and 4-aminopiperidine containing
      molecules. Selectivity for PKB vs PKA was observed with 4-aminopiperidine
      derivatives, and the most PKB-selective inhibitor (30-fold) showed significantly
      different bound conformations between PKA and PKA-PKB chimera.

PMID- 18345610
TI  - Synthesis and evaluation of novel polyaminocarboxylate-based antitumor agents.
AB  - Iron depletion, using iron chelators targeting transferrin receptor (TfR) and
      ribonucleotide reductase (RR), is proven to be effective in the treatment of
      cancer. We synthesized and evaluated novel polyaminocarboxylate-based chelators
      NETA, NE3TA, and NE3TA-Bn and their bifunctional versions C-NETA, C-NE3TA, and N
      NE3TA for use in iron depletion tumor therapy. The cytotoxic activities of the
      novel polyaminocarboxylates were evaluated in the HeLa and HT29 colon cancer cell
      lines and compared to the clinically available iron depletion agent DFO and the
      frequently explored polyaminocarboxylate DTPA. All new chelators except C-NETA
      displayed enhanced cytotoxicities in both HeLa and HT29 cancer cells compared to
      DFO and DTPA. Incorporation of the nitro functional unit for conjugation to a
      targeting moiety into the two potent non-functionalized chelators NE3TA and NE3TA
      Bn (C-NE3TA and N-NE3TA) was well-tolerated and resulted in a minimal decrease in
      cytotoxicity. Cellular uptake of C-NE3TA, examined using a confocal microscope,
      indicates that the chelator is taken up into HT29 cancer cells.

PMID- 18345611
TI  - Overcoming drug resistance to heme-targeted antimalarials by systematic side
      chain variation of 7-chloro-4-aminoquinolines.
AB  - Systematic variation of the branching and basicity of the side chain of
      chloroquine yielded a series of new 7-chloro-4-aminoquinoline derivatives
      exhibiting high in vitro activity against four different strains of P.
      falciparum. Many of the compounds tested showed excellent potency against
      chloroquine sensitive and resistant strains. In particular 4b, 5a, 5b, 5d, 17a,
      and 17b were found to be significantly more potent than chloroquine against the
      resistant strains Dd2 and FCB.

PMID- 18345612
TI  - 9-cyano-1-azapaullone (cazpaullone), a glycogen synthase kinase-3 (GSK-3)
      inhibitor activating pancreatic beta cell protection and replication.
AB  - Recently, the serine/threonine kinase glycogen synthase kinase-3 (GSK-3) emerged
      as a regulator of pancreatic beta cell growth and survival. On the basis of the
      previous observation that GSK-3 inhibitors like 1-azakenpaullone promote beta
      cell protection and replication, paullone derivatives were synthesized including
      1-aza-, 2-aza-, and 12-oxapaullone scaffolds. In enzymatic assays distinct 1
      azapaullones were found to exhibit selective GSK-3 inhibitory activity. Within
      the series of 1-azapaullones, three derivatives stimulated INS-1E beta cell
      replication and protected INS-1E cells against glucolipotoxicity induced cell
      death. Cazpaullone (9-cyano-1-azapaullone), the most active compound in the
      protection assays, also stimulated the replication of primary beta cells in
      isolated rat islets. Furthermore, cazpaullone showed a pronounced transient
      stimulation of the mRNA expression of the beta cell transcription factor Pax4, an
      important regulator of beta cell development and growth. These features
      distinguish cazpaullone as a unique starting point for the development of beta
      cell regenerative agents which might be useful in the treatment of diabetes.

PMID- 18345613
TI  - Mechanism of hydride donor generation using a Ru(II) complex containing an NAD+
      model ligand: pulse and steady-state radiolysis studies.
AB  - The mechanistic pathways of formation of the NADH-like [Ru(bpy) 2(pbnHH)] (2+)
      species from [Ru(bpy)2(pbn)](2+) were studied in an aqueous medium. Formation of
      the one-electron-reduced species as a result of reduction by a solvated electron
      (k=3.0 x 10(10) M(-1) s(-1)) or CO2(*-) (k=4.6 x 10(9) M(-1) s(-1)) or reductive
      quenching of an MLCT excited state by 1,4-diazabicyclo[2.2.2]octane (k=1.1 x
      10(9) M(-1) s(-1)) is followed by protonation of the reduced species (p K a =
      11). Dimerization (k7a=2.2 x 10(8) M(-1) s(-1)) of the singly reduced protonated
      species, [Ru(bpy) 2(pbnH(*))](2+), followed by disproportionation of the dimer as
      well as the cross reaction between the singly reduced protonated and
      nonprotonated species (k8= 1.2 x 10(8) M(-1) s(-1)) results in the formation of
      the final [Ru(bpy)2(pbnHH)](2+) product together with an equal amount of the
      starting complex, [Ru(bpy)2(pbn)](2+). At 0.2 degrees C, a dimeric intermediate,
      most likely a pi-stacking dimer, was observed that decomposes thermally to form
      an equimolar mixture of [Ru(bpy)2(pbnHH)](2+) and [Ru(bpy)2(pbn)](2+) (pH<9). The
      absence of a significant kinetic isotope effect in the disproportionation
      reaction of [Ru(bpy)2(pbnH(*))](2+) and its conjugate base (pH>9) indicates that
      disproportionation occurs by a stepwise pathway of electron transfer followed by
      proton transfer.

PMID- 18345614
TI  - New fluorogenic dansyl-containing calix[4]arene in the partial cone conformation
      for highly sensitive and selective recognition of lead(II).
AB  - A new efficient and highly selective fluorescent chemosensor for determination of
      Pb (2+) has been obtained by covalent attachment of two pendent proton-ionizable
      dansylcarboxamide groups to the calix[4]arene preorganized in the partial cone
      conformation. This geometry of the calixarene moiety was chosen on the basis of
      the prior (1)H NMR study of conformations adopted by the flexible dansyl
      containing prototype upon complexation with lead ion. In acidic MeCN-H2O (1:1
      v/v) solutions, the partial cone fluoroionophore allowed for detection of Pb (2+)
      at the levels as low as 2.5 ppb, which is totally compatible with the regulations
      of the U.S. Environmental Protection Agency and the World Health Organization on
      the limiting content of this hazardous pollutant in drinking water.

PMID- 18345615
TI  - Luminescence and mesogenic properties in crown-ether-isocyanide or carbene
      gold(I) complexes: luminescence in solution, in the solid, in the mesophase, and
      in the isotropic liquid state.
AB  - A crown ether isocyanide CNR (R = benzo-15-crown-5) has been synthesized by
      dehydration of the corresponding formamide. Substitution reactions with the
      appropriate gold(I) precursors afford the luminescent mononuclear derivatives
      [AuX(CNR)] (X = Cl, C 6F 5, Br, I), [Au(C 6F 4OCH 2C 6H 4OC nH 2 n+1 - p)(CNR)] (
      n = 4, 8, 10, 12), and [Au(C 6F 4OCH 2C 6H 2-3,4,5-(OC n H 2 n+1 ) 3(CNR)] ( n =
      4, 8, 12). X-ray diffraction studies of [AuCl(CNR)] show the molecules associated
      in a tetranuclear manner with an antiparallel orientation and gold-gold distances
      of 3.420 and 3.427 A (Au...Au...Au angles are 121.2 degrees ). These tetranuclear
      units generate infinite zigzag chains through longer Au...Au distances of 3.746 A
      and weak C-H...O nonclassic interactions. Nucleophilic attack to the coordinated
      isocyanide in [AuCl(CNR)] by methanol or a primary amine produces the carbene
      derivatives [AuCl{C((NHR)(OMe)}] and [AuCl{C(NHR')(NHR)}] (R' = Me, n-Bu). The
      ether crown in these complexes is able to coordinate sodium from NaClO 4,
      affording the corresponding bimetallic complexes (Na/Au = 1:1). The derivatives
      containing one alkoxy chain are liquid crystals, displaying a smectic C mesophase
      (for n > 4), whereas the trialkoxy derivatives display unidentified or smectic C
      mesophases, depending on the alkyl chain length. After complexation of sodium
      salts, the mesogenic behavior is lost. All of the derivatives are luminescent at
      room temperature in the solid state with emission maxima in the range 405-550 nm;
      they emit at 77 K from 410 to 572 nm. Only the ligand and the fluoroaryl
      complexes emit in solution at room temperature, but all of the compounds are
      luminescent at 77 K. Very interestingly, some fluoroaryl derivatives with alkoxy
      chains are luminescent not only in the solid, and in solution, but also in the
      mesophase, and in the isotropic liquid at moderate temperatures. These are the
      first metal complexes ever reported to show luminescence in the isotropic liquid
      state.

PMID- 18345616
TI  - Synthesis and characterization of luminescent zinc(II) and cadmium(II) complexes
      with N,S-chelating Schiff base ligands.
AB  - The reactions of zinc(II) acetate with a variety of 2-substituted
      benzothiazolines afforded tetrahedral mononuclear complexes with a N 2S 2 donor
      set, [Zn(RPhC(H) NC 6H 4 S) 2]. The obtained zinc(II) complexes can be divided
      into three groups based on the characteristics of the absorption spectra; Group 1
      (R = 2,4,6-triMe ( 1), 2,6-diCl ( 2)) showing an intense band at 250-300 nm and a
      weak band at 400-450 nm, Group 2 (R = 4-Cl ( 3), H ( 4), 4-Et ( 5), 4-OMe ( 6))
      showing two intense bands at 250-300 nm and a weak band at 400-450 nm, and Group
      3 (R = 4-NMe 2 ( 7), 4-NEt 2 ( 8)) showing an intense band at 250-300 nm and two
      very intense bands at 350-450 nm. The Group 2 and Group 3 complexes exhibited a
      strong emission on irradiating with ultraviolet light while the Group 1 complexes
      were not emissive at room temperature. However, all the zinc(II) complexes were
      luminescent in CH 2Cl 2/toluene glass at 77 K, and their emission peak energies
      were found to correlate with the Hammett constant of the substituent at para
      position of a pendent phenyl ring in each complex. Similar reactions of
      cadmium(II) acetate with 2-substituted benzothiazolines were also carried out to
      synthesize corresponding cadmium(II) complexes. While [Cd(RPhC(H) NC 6H 4 S) 2]
      (R = 2,4,6-triMe ( 9)) with bulky substituents at ortho positions of a pendent
      phenyl ring had a tetrahedral mononuclear structure, other cadmium(II) complexes
      [Cd 2(RPhC(H) NC 6H 4 S) 4] (R = 4-Et ( 10), 4-OMe ( 11), 4-NMe 2 ( 12))
      possessed S-bridged dinuclear structures. These cadmium(II) complexes, which are
      assumed to have a mononuclear structure in solution, showed photophysical
      properties similar to those of the corresponding zinc(II) complexes.

PMID- 18345617
TI  - Ru and Os complexes containing a P,N-donor heterotopic ligand: the effect of
      solvent on stereochemistry.
AB  - Ruthenium and osmium complexes of the general formula MCl 2(PyP) 2 (where PyP is
      the P,N- donor ligand 1-(2-diphenylphosphinoethyl)pyrazole) were synthesized from
      MCl 2(PPh 3) 3 (where M = Ru or Os). Three of the five possible stereoisomers of
      RuCl 2(PyP) 2 were synthesized and characterized in solution by multinuclear NMR
      spectroscopy, and the structure of these in the solid state was determined by X
      ray crystallography. Two of the analogous Os isomers were also synthesized. It
      was found that different solvents induced isomerization between these
      stereoisomers, indicating either lability of the chloride anion or hemilability
      of the PyP ligand. Bimetallic complexes of the general formula [Ru(mu-Cl)(PyP) 2]
      2[X] 2 were synthesized from chloride abstraction from RuCl 2(PyP) 2 using either
      silver (X = OSO 2CF 3, BF 4) or sodium (X = BPh 4) salts. The osmium analogue of
      the Ru bimetallic complexes, [Os(mu-Cl)(PyP) 2] 2[BPh 4] 2, was also synthesized.
      Solid-state structures were obtained using X-ray crystallography for the osmium
      bimetallic complex and the ruthenium bimetallic complex where X = OSO 2CF 3. The
      hemilability of PyP was demonstrated through the synthesis of RuCl 2(CO)(kappa
      (1)- P-PyP)(kappa (2)- P, N-PyP), which contains one pendant PyP ligand, bound
      through the P-donor atom.

PMID- 18345618
TI  - Helical supramolecular assemblies of {2,4,6-[Cp*Rh(E2-1,2
      C2B10H10)(NC5H4CH2S)]3(triazine)} (E = S, Se) shaped by Cp*-Toluene-Cp* pi
      stacking forces and BH-pyridine hydrogen bonding.
AB  - Polycarborane-substituted molecules [Cp*Rh{E 2C 2(B 10H 10)}] 3(tpst) [E = S (
      2a), Se ( 2b)] were synthesized and characterized. 2a and 2b form toluene
      solvates in the solid state showing infinitely connected [( 2a, b)-(toluene)]
      infinity helices. The chains of these supramolecules are held together by Cp*
      toluene-Cp* pi-stacking interactions of two of the three Cp* ligands of the bell
      shaped 2a and 2b molecules. Unconventional BH (delta-)-pyridyl (delta+) aromatic
      hydrogen bonding enforces the bell-shapes of the molecular units, and the Cp*
      conformations are expected to induce the supramolecular structures.

PMID- 18345619
TI  - Liquid azide salts.
AB  - Ionic liquid azides from azidoethyl, alkyl, and alkenyl substituted derivatives
      of 1,2,4- and 1,2,3-amino-triazoles were prepared and examined for the first time
      to investigate their structural and physical properties. All reported salts
      possess melting points below 100 degrees C. The unique character of these newly
      discovered ionic liquid azides is based upon the fact that these molecules are
      not simple protonated salts like previously reported substituted hydrazinium
      azides. The presence of quaternary nitrogen confers both thermal stability and
      negligible volatility.

PMID- 18345620
TI  - Molecular structures of the digermanes Me2XGeGeXMe2 (X = Me, Cl, and H): an ab
      initio study combined with experimental investigation by Raman spectroscopy and
      gas electron diffraction.
AB  - Ab initio calculations were carried out to investigate the potential-energy
      surface for internal rotation of the methylated digermanes hexamethyldigermane
      Me(3)GeGeMe(3) ( 1), dichlorotetramethyldigermane Me(2)ClGeGeClMe(2) ( 2), and
      tetramethyldigermane Me(2)HGeGeHMe(2) ( 3). Different basis sets [6-31+G(d), SDD,
      aug-cc-pVTZ] were employed at the DFT and MP2 levels of theory to optimize
      structures and to calculate energies and vibrational frequencies. For 1, one
      minimum representing a staggered structure was located on the potential-energy
      surface. For 2 and 3, antiperiplanar conformations with C 2 symmetry were found
      to be the global minima. Additionally, synclinal minima were located for 2 and 3
      when certain basis sets were employed. Determination of structural parameters in
      the gas phase by gas electron diffraction confirmed the computed predictions for
      all three compounds. For 2 and 3, the ratios of antiperiplanar to synclinal
      conformer were detected to be 90:10 (328 K) and 72:28 (293 K), respectively, by
      gas electron diffraction. The experimentally determined GeGe bond lengths in 1,
      2, and 3 in the gas phase are 241.4(1), 242.7(2) (averaged for antiperiplanar and
      synclinal), and 241.7(1) pm (equal for antiperiplanar and synclinal). Only
      averaged structures were observed, using Raman spectroscopy, for 2 and 3 because
      the wavenumber differences are small between conformers and there is only a small
      contribution from the second conformer in each case. For 2, the crystal structure
      was also determined by X-ray diffraction. An anticlinal structure (with Cl atoms
      eclipsing the C atoms) was found with a GeGe bond length of 242.1 pm.

PMID- 18345621
TI  - Similar K@Au10Sn10 polyhedra in the markedly different structures of KAu4Sn6 and
      KAu3Sn3. syntheses and characterization.
AB  - These compounds were synthesized by high-temperature reactions of the elements in
      welded Ta tubes and characterized by X-ray diffraction methods and linear muffin
      tin orbital (LMTO) calculations. AAu4Sn6 (A = K, Rb) have a new structural type
      (Fddd, Z = 8), and KAu3Sn3 (Pmmn, Z = 2) is isostructural with SrAu3In3. Both
      orthorhombic structures contain similar condensed K@Au10Sn10 polyhedral building
      blocks, which can be described as overall 6-8-6 arrangements of planar rings or,
      alternatively, as hexagonal prisms centered by K and augmented about the waists
      by 8-rings of Au and Sn. However, the 3D Au-Sn networks differ appreciably in
      both composition and the modes of condensation. In KAu3Sn3, the prisms stack by
      sharing both hexagonal faces with like neighbors along a, whereas those in
      KAu4Sn6 condense in a complex zigzag network. Compared with related indium
      systems, the structure change from KAu4In6 ( P_6m2, Z = 1) to KAu4Sn6 apparently
      illustrates the effect of complex factors such as atom size and valence electron
      counts on structure, whereas the SrAu3In3 and KAu3Sn3 pair are isotypic. Both
      compounds are Pauli-paramagnetic and inert to water at room temperature for
      several days. Tight-binding electronic structure (LMTO) calculations emphasize
      the dominance and strength of the heteroatomic Au-Sn bonding.

PMID- 18345622
TI  - Trithio-chloro molybdate [MoClS3]-: a versatile precursor for molybdenum
      trisulfido complexes.
AB  - The reaction of trithiomolybdate [PPh 4] 2[MoOS 3] ( 1) with 2 equiv of
      trimethylchlorosilane generated trithio-chloro molybdate [PPh 4][MoClS 3] ( 2) in
      high yield, by way of a siloxy complex [PPh 4][Mo(OSiMe 3)S 3] ( 3). This
      intriguing reaction provided us with a convenient entry into a series of
      mononuclear molybdenum trisulfido complexes, [PPh 4][MoS 3X] ( 4, X = Cp*; 6a, X
      = S (t) Bu; 6b, X = SPh; 6c, X = SMes (Mes = mesityl); 6d, X = STip (Tip = 2,4,6
      triisopropylphenyl); 6e, X = SDmp (Dmp = 2,6-dimesitylphenyl); 7, X = NPh 2; 8a,
      X = O (t) Bu; 8b, X = OPh; 8c, X = OC(CH 2) (t) Bu; 8d, X = OC(CH 2)Ph), which
      were obtained by the reactions of 2 with the corresponding potassium salts. In a
      similar manner, a citrate complex [PPh 4][MoS 3(Me 3cit)] ( 9, Me 3cit = OC(CH
      2CO 2Me) 2(CO 2Me)) was synthesized, which may model the molybdenum site of the
      nitrogenase FeMo-cofactor. The molecular structures of 2, 6c, 7, 8a, 8b, 8c, and
      9 were determined by X-ray crystallography.

PMID- 18345623
TI  - Unprecedented dinuclear tin derivative of deprotonated beta-cyclodextrins.
AB  - Two unprecedented dinuclear tin compounds containing deprotonated beta
      cyclodextrins have been constructed by using different organotin and inorganotin
      precursors under solvothermal conditions, which display two dinuclear airscrew
      like structures with different packing modes.

PMID- 18345624
TI  - V4O10: spectroscopic fingerprint of a well-defined, molecular metaloxo aggregate.
AB  - V4O10 can be considered as a molecular model for oxovanadium clusters deposited
      on the surfaces of corresponding heterogeneous catalysts, and here its
      generation, matrix isolation, and comprehensive characterization by IR, Raman,
      and UV/vis spectroscopy are described.

PMID- 18345625
TI  - First structural evidence of actinide-nitrite coordination.
AB  - The first nitrite complex of actinide metal, {C(NH 2)3}2[NpO 2(NO 2)(Pic)2], was
      synthesized, and its crystal structure was determined using X-ray diffractometry
      and confirmed by NIR and IR spectroscopies. Main crystallographic data: space
      group P1, triclinic, a = 8.9329(1) A, b = 11.6669(2) A, c = 11.6698(2) A, alpha =
      68.080(1) degrees, beta = 88.213(1) degrees, gamma = 73.254(1) degrees, V =
      1076.45(3) A (3), and Z = 2.

PMID- 18345626
TI  - Blue or green glowing crystals of the cation [Au{C(NHMe)2}2]+. Structural effects
      of anions, hydrogen bonding, and solvate molecules on the luminescence of a two
      coordinate gold(I) carbene complex.
AB  - Depending upon the crystallization conditions, [Au{C(NHMe) 2} 2](AsF 6) forms
      colorless crystals that display a blue or green luminescence. The difference
      involves the type of solvate molecule that is incorporated into the crystal and
      the structure of the chains of cations that are formed upon crystallization. The
      crystallographically determined structures of blue-glowing [Au{C(NHMe) 2} 2](AsF
      6).0.5(benzene), blue-glowing [Au{C(NHMe) 2} 2](AsF 6).0.5(acetone), green
      glowing [Au{C(NHMe) 2} 2](AsF 6).0.5(chlorobenzene), and blue-glowing, solvate
      free [Au{C(NHMe) 2} 2](EF 6), E = P, As, Sb are reported. All pack with the
      cations forming extended columns, which may be linear or bent, but all show
      significant aurophilic interactions. The blue-glowing crystals have ordered
      stacks of cations with some variation in structural arrangement whereas the green
      glowing crystals have disorder in their stacking pattern. Although there is
      extensive hydrogen bonding between the cations and anions in all structures, in
      the solvated crystals, the solvate molecules occupy channels but make no hydrogen
      bonded contacts. The emission spectra of these new salts taken at 298 and 77 K
      are reported.

PMID- 18345627
TI  - Multipoint anchoring of the [2.2.2.2]metacyclophane motif to a gold surface via
      self-assembly: coordination chemistry of a cyclic tetraisocyanide revisited.
AB  - A one-pot transformation of bis(2-isocyano-3-methylphenyl)ethane affords gram
      quantities of 8,16,24,32-tetraisocyano[2.2.2.2]metacyclophane ( 3). The solid
      state structure of 3 is remarkably close to the lowest energy conformation found
      on the potential energy landscape for 3 by DFT. In solution, the structure of
      metacyclophane 3 is mobile but can be locked in a rectangular gauche- anti-
      gauche- anti conformation by coordination of the isocyanide substituents to the
      [W(CO) 5] units to give [M] 4(mu 4-eta (1):eta (1):eta (1):eta (1)- 3) ( 5). The
      tetranuclear [M] 4(mu 4-eta (1):eta (1):eta (1):eta (1)- 3) motif featured in
      crystallographically characterized 5 may be present in several insoluble
      complexes of 3 previously described as mononuclear eta (4) species. A self
      assembled monolayer of metacyclophane 3 is formed upon exposing a solution of 3
      to the gold(111) surface with no precautions to exclude air or light. The
      monolayer nature of the film was confirmed by optical ellipsometry. The
      isocyanide stretching band for 3 shifts from 2119 cm (-1) in solution to 2175 cm
      (-1) upon chemisorption to metallic gold. The FTIR spectrum of the film indicates
      interaction of 3 with the gold surface via all four of its isocyanide anchors. No
      gold-facilitated oxidation of the -NC junctions was detected under ambient
      conditions. The energy cost associated with accessing the conformations of 3
      suitable for mu 4-eta (1):eta (1):eta (1):eta (1) interaction of the molecule
      with the Au(111) surface is under 8 kcal/mol, a value that can be easily offset
      by formation of a gold-isocyanide bond. Two different mu 4-eta (1):eta (1):eta
      (1):eta (1) coordination arrangements of 3 with respect to gold atoms on the
      (111) face of the fcc Au lattice are suggested.

PMID- 18345628
TI  - Polyoxometalate embedding of a tetraruthenium(IV)-oxo-core by template-directed
      metalation of [gamma-SiW10O36]8-: a totally inorganic oxygen-evolving catalyst.
AB  - Solid state and solution evidence confirms the embedding of an adamantane-like,
      Ru4O6 fragment by the divacant, gamma-decatungstosilicate ligand. The resulting
      complex catalyzes water oxidation to oxygen with TON up to 500 and TOF > 450 h-1.

PMID- 18345629
TI  - Hadamard amino-acid-type edited NMR experiment for fast protein resonance
      assignment.
AB  - An original Hadamard-encoding scheme allows discrimination among seven amino acid
      types in a single two-dimensional NMR experiment. Combined with hyperdimensional
      NMR techniques, this presents a promising new method for fast, automated backbone
      resonance assignment of proteins in only a few hours time.

PMID- 18345630
TI  - Oligonucleotide-stabilized Ag nanocluster fluorophores.
AB  - Single-stranded oligonucleotides stabilize highly fluorescent Ag nanoclusters,
      with emission colors tunable via DNA sequence. We utilized DNA microarrays to
      optimize these scaffold sequences for creating nearly spectrally pure Ag
      nanocluster fluorophores that are highly photostable and exhibit great buffer
      stability. Five different nanocluster emitters have been created with tunable
      emission from the blue to the near-IR and excellent photophysical properties.
      Ensemble and single molecule fluorescence studies show that oligonucleotide
      encapsulated Ag nanoclusters exhibit significantly greater photostability and
      higher emission rates than commonly used cyanine dyes.

PMID- 18345631
TI  - Comparison of the glucosinolate-myrosinase systems among daikon (Raphanus
      sativus, Japanese white radish) varieties.
AB  - Myrosinase is a cytosolic plant enzyme present in daikon ( Raphanus sativus,
      Japanese white radish) roots that hydrolyzes 4-methylthio-3-butenyl glucosinolate
      (MTBGLS) into the natural pungent agent 4-methylthio-3-butenyl isothiocyanate
      (MTBITC), which possesses antimicrobial, antimutagenic, and anticarcinogenic
      properties. The concentration of MTBGLS, myrosinase activity, and production of
      MTBITC in seven daikon varieties (one conventional and six heirlooms) were
      determined to rank the activity of the glucosinolate-myrosinase system and
      identify critical factors influencing the production of MTBITC. The six heirloom
      varieties produced 2.0-11.5 times higher levels of MTBITC as compared to the
      conventional variety, Aokubi, which is consumed by the present Japanese
      population. The myrosinase was located exclusively in the outer epidermal layer
      in Aokubi, and MTBGLS was widely distributed throughout the root tissue. Although
      the skin is a potentially rich source of myrosinase in Aokubi, the skin is
      usually peeled off in the current practice of preparing daikon for cooking. New
      practices are therefore proposed for the preparation of daikon tubers that
      eliminate the peeling of the skin to avoid removing the enzyme needed to convert
      MTBGLS to the health-beneficial MTBITC. It is also concluded that the consumption
      of heirloom daikon varieties in addition to changes in food preparation will
      optimize the health benefits of daikon.

PMID- 18345632
TI  - Novel effects of a single administration of ferulic acid on the regulation of
      blood pressure and the hepatic lipid metabolic profile in stroke-prone
      spontaneously hypertensive rats.
AB  - We studied the effects of a single oral administration of ferulic acid (FA) on
      the blood pressure (BP) and lipid profile in stroke-prone spontaneously
      hypertensive rats (SHRSP). Male 12-week-old SHRSP were administered FA (9.5 mg/kg
      of body weight) and distilled water as the control (C) (1 mL) via a gastric tube.
      The hypotensive effect of FA was observed at the lowest value after 2 h
      administration. A decrease in the angiotensin-1-converting enzyme (ACE) activity
      in the plasma corresponded well with the reduction of BP. Plasma total
      cholesterol and triglyceride levels were lower after 2 h administration. The mRNA
      expression of genes involved in lipid and drug metabolism was downregulated in
      the FA group. These results suggest that oral administration of FA appears
      beneficial in improving hypertension and hyperlipidemia.

PMID- 18345633
TI  - Protein-protein interactions during high-moisture extrusion for fibrous meat
      analogues and comparison of protein solubility methods using different solvent
      systems.
AB  - Soy protein, mixed with gluten and starch, was extruded into fibrous meat
      analogues under high-moisture and high-temperature conditions. The protein
      solubility of samples collected at different extruder zones and extrudates made
      with different moistures was determined by 11 extraction solutions consisting of
      6 selective reagents and their combinations: phosphate salts, urea, DTT,
      thiourea, Triton X-100, and CHAPS. Protein solubility by most extractants showed
      decreasing patterns as the material passed through the extruder, but the solution
      containing all 6 reagents, known as isoelectric focus (IEF) buffer, solubilized
      the highest levels and equal amounts of proteins in all samples, indicating that
      there are no other covalent bonds involved besides disulfide bonds. With regard
      to relative importance between disulfide bonds and non-covalent interactions,
      different conclusions could be made from protein solubility patterns, depending
      on the type of extracting systems and a baseline used for comparison. The
      observation points out pitfalls and limitation of current protein solubility
      methodology and explains why controversy exists in the literature. Using the IEF
      buffer system with omission of one or more selective reagents is considered to be
      the right methodology to conduct protein solubility study and thus recommended.
      Results obtained with this system indicate that disulfide bonding plays a more
      important role than non-covalent bonds in not only holding the rigid structure of
      extrudates but also forming fibrous texture. The sharpest decrease in protein
      solubility occurred when the mix passed through the intermediate section of the
      extruder barrel, indicating formation of new disulfide bonds during the stage of
      dramatic increase in both temperature and moisture. After this stage, although
      the physical form of the product might undergo change and fiber formation might
      occur as it passed through the cooling die, the chemical nature of the product
      did not change significantly.

PMID- 18345634
TI  - Changes in color and phenolic compounds during the raisining of grape cv. Pedro
      Ximenez.
AB  - Changes in color parameters and phenolic compounds during the sun-drying grape
      raisining of cv. Pedro Ximenez to obtain sweet wines are studied. Browning
      increases during the process as a result of the contribution to a greater extent
      of the low and medium molecular size polymers than the high molecular size
      polymers. Raisining decreases hue and lightness and increases chroma, all
      measured as CIELab parameters, indicating a color change to dark reddish hues
      that is also preferentially due to low and medium molecular size polymers. Most
      of the phenols studied increase in concentration during raisining, essentially
      through the concentration effect resulting from the loss of water in the grapes.
      The concentration changes, however, are comparatively small for hydroxycinnamic
      esters and flavan-3-ol derivatives, suggesting that these phenolic fractions
      undergo predominantly oxidative degradation reactions by enzymatic pathways,
      contributing strongly to the browning of grapes.

PMID- 18345635
TI  - Extraction of grape seed oil using compressed carbon dioxide and propane:
      extraction yields and characterization of free glycerol compounds.
AB  - The main objective of this work was to compare the extraction of grape seed oil
      with compressed carbon dioxide and propane on the extraction yields and chemical
      characteristics of free glycerol compounds. The experiments were performed in a
      laboratory scale unit in the temperature range of 30 to 60 degrees C and
      pressures from 60 to 254 bar. The results showed that propane is a more suitable
      solvent for grape seed oil extraction than carbon dioxide, as higher extractions
      yields and a very fast kinetic of extraction were achieved with this solvent. In
      relation to compressed carbon dioxide extractions, both temperature and density
      presented a very pronounced and positive effect on the extraction yield. The oils
      extracted were analyzed qualitatively and quantitatively with regard to the free
      glycerol compounds, mainly fatty acids, ethyl, and methyl esters. The results
      showed that these compounds are present in low concentration in vegetable oil
      (<3%) and that, in general, samples extracted with propane present a smaller
      amount of peaks of free glycerol compounds in the oil than samples extracted with
      carbon dioxide.

PMID- 18345636
TI  - Neutral styrene divinylbenzene copolymers for adsorption of toxins in liver
      failure.
AB  - In artificial extracorporeal liver support systems, albumin-bound toxins such as
      bilirubin, bile acids, or aromatic amino acids are removed by adsorption to
      polymer beads. To overcome the potential weaknesses of anion exchange polymers
      currently used in liver support, namely, binding of heparin and activation of
      coagulation, we prepared two series of neutral polystyrene divinylbenzene resins
      with average pore sizes of 5-6 and 8-9 nm, respectively. In in vitro experiments
      using human plasma spiked with bilirubin, cholic acid, tryptophan, and phenol, we
      found that only pores larger than 5-6 nm were accessible to strongly albumin
      bound substances, such as bilirubin. On the other hand, less strongly albumin
      bound substances, such as bile acids, were efficiently bound by polymers of the
      small pore size range due to a higher accessible surface area. None of the
      neutral resins bound significant amounts of heparin. To assess the influence of
      the polymers on activation of coagulation, generation of thrombin-antithrombin
      complexes (TAT) was measured at different citrate concentrations. While none of
      the neutral polymers induced TAT generation, TAT levels were significantly
      elevated after incubation of plasma with an anion exchange polymer that is in
      clinical use for extracorporeal liver support. Binding characteristics of the
      neutral resins for the natural anticoagulants protein C and antithrombin showed
      remarkable differences, with weak binding of antithrombin but strong removal of
      protein C, not only for the anion exchanger, but also for neutral polymers of the
      large pore size range. In conclusion, neutral polystyrene divinylbenzene polymers
      with a pore size larger than 5-6 nm are efficient adsorbents for albumin-bound
      toxins that do not induce generation of thrombin-antithrombin complexes.

PMID- 18345637
TI  - Polysaccharide-based hydrogels: preparation, characterization, and drug
      interaction behaviour.
AB  - Oxidized alginate (ADA) and oxidized alginate blended with chitosan (ADA-Chit)
      were prepared in the presence of borax and CaCl 2, and their interactions with an
      antifolate drug, pyrimethamine (PYR), have been investigated. Tablets with a mean
      diameter of 1.2 +/- 0.06 cm were produced and drug interactions were performed in
      dimethyl sulfoxide (DMSO) using isothermal titration calorimetry (ITC). From ITC
      responses, the enthalpy changes of interaction PYR/materials, Delta int H, have
      been determined and were found to be -11.73 +/- 0.517 kJ mol (-1) for ADA and 
      4.86 +/- 0.156 kJ mol (-1) for ADA-Chit. The PYR encapsulation of approximately
      75% was achieved for both materials, as measured by UV spectrometer.

PMID- 18345638
TI  - Impact of pH on plasma protein binding in equilibrium dialysis.
AB  - Many pharmacokinetic analyses require unbound plasma concentrations, including
      prediction of clearance, volume of distribution, drug-drug interactions, brain
      uptake analysis, etc. It is most often more convenient to measure the total drug
      concentration in plasma rather than the unbound drug concentration. To arrive at
      unbound plasma concentrations, separate in vitro determinations of the plasma
      protein binding of a drug are usually carried out in serum or in plasma, and the
      plasma pharmacokinetic results are then mathematically adjusted by this fraction
      unbound ( f u,p). Plasma protein binding or the drug fraction unbound in plasma (
      f u,p) is known to be affected by protein, drug, free fatty acid concentrations,
      lipoprotein partitioning, temperature, pH, and the presence or absence of other
      drugs/displacing agents within plasma samples. Errors in f u,p determination
      caused by lack of adequate pH control in newer assay formats for plasma protein
      binding (e.g., 96-well equilibrium thin walled polypropylene dialysis plates)
      will have significant drug-specific impact on these pharmacokinetic calculations.
      Using a diverse set of 55 drugs and a 96-well equilibrium dialysis plate format,
      the effect of variable pH during equilibrium dialysis experiments on measured
      values of f u,p was examined. Equilibrium dialysis of human plasma against
      Dulbecco's phosphate buffered saline at 37 degrees C under an air or 10% CO 2
      atmosphere for 22 h resulted in a final pH of approximately 8.7 and 7.4,
      respectively. The ratio of f u,p at pH 7.4 (10% CO 2) vs pH 8.7 (air) was >or=2.0
      for 40% of the 55 compounds tested. Only one of the 55 compounds tested had a
      ratio <0.9. Select compounds were further examined in rat and dog plasma. In
      addition, physicochemical properties were calculated for all compounds using
      ACD/Labs software or Merck in-house software and compared to plasma protein
      binding results. Changes in plasma protein binding due to pH increases which
      occurred during the equilibrium dialysis experiment were not species specific but
      were drug-specific, though nonpolar, cationic compounds had a higher likely hood
      of displaying pH-dependent binding. These studies underscore the importance of
      effectively controlling pH in plasma protein binding studies.

PMID- 18345639
TI  - Asymmetric synthesis of (+)-pyrido[3,4-b]homotropane.
AB  - (+)-pyrido[3,4- b]homotropane (PHT) was efficiently constructed in 12 steps from
      N, N-diisopropylisonicotinamide. The synthesis features (i) RCM reaction in
      installing the homotropane skeleton, (ii) Snieckus ortho-lithiation of N, N
      diisopropylisonicotinamide followed by acylation, (iii) Myer reduction of bulky
      tertiary amide to alcohol with LiBH 3NH 2, and (iv) utilization of L-glutamic
      acid to introduce and establish the requisite stereogenic centers.

PMID- 18345640
TI  - Hydrogen bonding vs steric gearing in a hexasubstituted benzene.
AB  - Treatment of hexakis(bromomethyl)benzene with excess NaN 3, followed by
      hydrogenation of the resultant polyazide, affords hexamine 3 in high yield.
      Coupling to six equivalents of nonanoic acid provides hexamide 5 without
      chromatographic purification. The NH resonance of 5 appears far downfield
      (approximately 9.7 ppm) in CDCl3 and is unaffected by changes in concentration or
      by addition of chloride or trifluoromethanesulfonate ions. DFT calculations
      predict that 5 exists as a bowl, with all six substituents intramolecularly H
      bonded together on one side of the plane defined by the anchoring arene.

PMID- 18345641
TI  - ent-Kaurane Diterpenoids from Isodon nervosus.
AB  - A pentacyclic ent-kauranoid, nervonin A ( 1), with an unprecedented cyclobutane
      moiety in the structure, and nine other new ent-kaurane diterpenoids, nervonins B
      J ( 2- 10), along with 10 known ones ( 11- 20), were isolated from Isodon
      nervosus. Their structures were elucidated by detailed spectroscopic analysis.
      All diterpenoids were assayed for their cytotoxicity against K562, A549, and
      HepG2 human cell lines. Compounds 2, 11, 16, 17, and 20 showed significant
      cytotoxicity.

PMID- 18345642
TI  - Brianodins A-D, briarane-type diterpenoids from soft coral Pachyclavularia sp.
AB  - Four new briarane-type diterpenoids, brianodins A-D ( 1- 4), were isolated from a
      soft coral, Pachyclavularia sp., and the structures and relative stereochemistry
      of 1- 4 were elucidated on the basis of spectroscopic data. The absolute
      configurations of 3 and 4 were assigned by the MTPA method. Brianodin A ( 1)
      showed a modest cytotoxicity.

PMID- 18345643
TI  - Role of helix B residues in interfacial activation of a bacterial
      phosphatidylinositol-specific phospholipase C.
AB  - The Bacillus thuringiensis phosphatidylinositol-specific phospholipase C (PI
      PLC), an interfacial enzyme associated with prokaryotic infectivity, is activated
      by binding to zwitterionic surfaces, particularly phosphatidycholine (PC). Two
      tryptophan residues (Trp47 in the two-turn helix B and Trp242 in a disordered
      loop) at the rim of the barrel structure are critical for this interaction. The
      helix B region (Ile43 to Gly48) in wild-type PI-PLC orients the side chains of
      Ile43 and Trp47 so that they pack together and form a hydrophobic protrusion from
      the protein surface that likely facilitates initial membrane binding. In previous
      studies we reported that in the crystal structure of the dimeric W47A/W242A
      mutant, which is unable to bind to PC, the helix B region has been reorganized by
      the mutation into an extended loop. Here we report the construction and
      characterization (catalytic activity, fluorescence, and NMR studies) of a series
      of PI-PLC mutants targeting helix B residues and surrounding regions to explore
      what is needed to stabilize the "membrane-active" conformation of the helix B
      region. Results strongly suggest that, while hydrophobic groups and presumably an
      intact helix B are critical for the initial binding of PI-PLC to membranes,
      disruption of helix B to allow enzyme dimerization is what leads to the activated
      PI-PLC conformation.

PMID- 18345644
TI  - Close encounters between two nanoshells.
AB  - Plasmonic nanoparticle pairs known as "dimers" embody a simple system for
      generating intense nanoscale fields for surface enhanced spectroscopies and for
      developing an understanding of coupled plasmons. Individual nanoshell dimers in
      directly adjacent pairs and touching geometries show dramatically different
      plasmonic properties. At close distances, hybridized plasmon modes appear whose
      energies depend extremely sensitively on the presence of a small number of
      molecules in the interparticle junction. When touching, a new plasmon mode
      arising from charge transfer oscillations emerges. The extreme modification of
      the overall optical response due to minute changes in very reduced volumes opens
      up new approaches for ultrasensitive molecular sensing and spectroscopy.

PMID- 18345645
TI  - Zr/ZrO2 sensors for in situ measurement of pH in high-temperature and -pressure
      aqueous solutions.
AB  - The aim of this study is to develop new pH sensors that can be used to test and
      monitor hydrogen ion activity in hydrothermal conditions. A Zr/ZrO2 oxidation
      electrode is fabricated for in situ pH measurement of high-temperature aqueous
      solutions. This sensor responds rapidly and precisely to pH over a wide range of
      temperature and pressure. The Zr/ZrO2 electrode was made by oxidizing zirconium
      metal wire with Na2CO3 melt, which produced a thin film of ZrO2 on its surface.
      Thus, an oxidation-reduction electrode was produced. The Zr/ZrO2 electrode has a
      good electrochemical stability over a wide range of pH in high-temperature
      aqueous solutions when used with a Ag/AgCl reference electrode. Measurements of
      the Zr/ZrO2 sensor potential against a Ag/AgCl reference electrode is shown to
      vary linearly with pH between temperatures 20 and 200 degrees C. The slope of the
      potential versus pH at high temperature is slightly below the theoretical value
      indicated by the Nernst equation; such deviation is attributed to the fact that
      the sensor is not strictly at equilibrium with the solution to be tested in a
      short period of time. The Zr/ZrO2 sensor can be calibrated over the conditions
      that exist in the natural deep-seawater. Our studies showed that the Zr/ZrO2
      electrode is a suitable pH sensor for the hydrothermal systems at midocean ridge
      or other geothermal systems with the high-temperature environment. Yttria
      stabilized zirconia sensors have also been used to investigate the pH of
      hydrothermal fluids in hot springs vents at midocean ridge. These sensors,
      however, are not sensitive below 200 degrees C. Zr/ZrO2 sensors have wider
      temperature range and can be severed as good alternative sensors for measuring
      the pH of hydrothermal fluids.

PMID- 18345646
TI  - Trace level detection of compounds related to the chemical weapons convention by
      1H-detected 13C NMR spectroscopy executed with a sensitivity-enhanced, cryogenic
      probehead.
AB  - Two-dimensional 1H-13C HSQC (heteronuclear single quantum correlation) and fast
      HMQC (heteronuclear multiple quantum correlation) pulse sequences were
      implemented using a sensitivity-enhanced, cryogenic probehead for detecting
      compounds relevant to the Chemical Weapons Convention present in complex
      mixtures. The resulting methods demonstrated exceptional sensitivity for
      detecting the analytes at trace level concentrations. 1H-13C correlations of
      target analytes at < or = 25 microg/mL were easily detected in a sample where the
      1H solvent signal was approximately 58,000-fold more intense than the analyte 1H
      signals. The problem of overlapping signals typically observed in conventional 1H
      spectroscopy was essentially eliminated, while 1H and 13C chemical shift
      information could be derived quickly and simultaneously from the resulting
      spectra. The fast-HMQC pulse sequences generated magnitude mode spectra suitable
      for detailed analysis in approximately 4.5 h and can be used in experiments to
      efficiently screen a large number of samples. The HSQC pulse sequences, on the
      other hand, required roughly twice the data acquisition time to produce suitable
      spectra. These spectra, however, were phase-sensitive, contained considerably
      more resolution in both dimensions, and proved to be superior for detecting
      analyte 1H-13C correlations. Furthermore, a HSQC spectrum collected with a
      multiplicity-edited pulse sequence provided additional structural information
      valuable for identifying target analytes. The HSQC pulse sequences are ideal for
      collecting high-quality data sets with overnight acquisitions and logically
      follow the use of fast-HMQC pulse sequences to rapidly screen samples for
      potential target analytes. Use of the pulse sequences considerably improves the
      performance of NMR spectroscopy as a complimentary technique for the screening,
      identification, and validation of chemical warfare agents and other small
      molecule analytes present in complex mixtures and environmental samples.

PMID- 18345648
TI  - Tropospheric oxidation of ethyne and But-2-yne. 1. Theoretical mechanistic study.
AB  - This paper (part 1) and the following one (part 2) aim to assess the viability of
      some tropospheric oxidation channels for two symmetrical alkynes, ethyne
      (acetylene) and but-2-yne. Paper 1 defines the features of the DFT(B3LYP)/6
      311G(3df,2p) energy hypersurface and qualitatively considers the practicability
      of different pathways through the estimate of free energy barriers. Paper 2 will
      assess this in more detail by way of master equation simulations. Oxidized in the
      presence of HO and O2 (with the possible intervention of NO), ethyne and but-2
      yne are known to produce mainly glyoxal or dimethylglyoxal and, to a lesser
      extent, formic or acetic acid. The initial attack by HO gives an adduct, from
      which several pathways (1a-c, 2a-e) originate. Pathway 1a passes through the 2
      oxoethyl (vinoxyl) radical, or the analogous dimethyl-substituted intermediate,
      which could in principle undergo O2 addition (and subsequently, but through a
      demanding step, give the dialdehydes). However, in paper 2 it is assessed that
      the vinoxyl, as a nonthermalized intermediate, will preferentially follow
      unimolecular pathways to ketene or acetyl. Pathway 2a is the most important
      pathway: a very steep free energy cascade, started by O2 addition to the initial
      HO adduct with a concerted barrierless 1,5 H shift, gives a
      hydroperoxyalkenyloxyl radical intermediate. Peroxy bond cleavage finally
      produces the dialdehydes and regenerates HO. Pathways 2b and 2c originate from O2
      addition to the initial HO adduct and produce, via different ring closures,
      either dioxetanyl or alkyl dioxiranyl radicals, respectively. Two subsequent
      fragmentations occur in both cases and give the carboxylic acids and a carbonyl
      radical, which can indirectly generate hydroxyl. Two further pathways (1c and 2e)
      see NO intervention onto the peroxyl radicals formed along pathways 1 and 2. Both
      could enhance dialdehyde production, while simultaneously depressing the
      carboxylic acid yield.

PMID- 18345647
TI  - Glucose and lactate biosensors for scanning electrochemical microscopy imaging of
      single live cells.
AB  - We have developed glucose and lactate ultramicroelectrode (UME) biosensors based
      on glucose oxidase and lactate oxidase (with enzymes immobilized onto Pt UMEs by
      either electropolymerization or casting) for scanning electrochemical microscopy
      (SECM) and have determined their sensitivity to glucose and lactate,
      respectively. The results of our evaluations reveal different advantages for
      sensors constructed by each method: improved sensitivity and shorter
      manufacturing time for hand-casting, and increased reproducibility for
      electropolymerization. We have acquired amperometric approach curves (ACs) for
      each type of manufactured biosensor UME, and these ACs can be used as a means of
      positioning the UME above a substrate at a known distance. We have used the
      glucose biosensor UMEs to record profiles of glucose uptake above individual
      fibroblasts. Likewise, we have employed the lactate biosensor UMEs for recording
      the lactate production above single cancer cells with the SECM. We also show that
      oxygen respiration profiles for single cancer cells do not mimic cell topography,
      but are rather more convoluted, with a higher respiration activity observed at
      the points where the cell touches the Petri dish. These UME biosensors, along
      with the application of others already described in the literature, could prove
      to be powerful tools for mapping metabolic analytes, such as glucose, lactate,
      and oxygen, in single cancer cells.

PMID- 18345649
TI  - Oxidation of ethyne and But-2-yne. 2. Master equation simulations.
AB  - The aim of this study is to improve understanding of the tropospheric oxidation
      of ethyne (acetylene, C2H2) and but-2-yne, which takes place in the presence of
      HO and O2. The details of the potential energy hypersurface have been discussed
      in a previous article [Maranzana et al., J. Phys. Chem. A 2008, 112, XXXX]. For
      both molecules, the initial addition of HO radical to the triple bond is followed
      by addition of O2 to form peroxyl radicals. In both reaction systems, the peroxyl
      radicals take two isomeric forms, E1 and E2 for ethyne and e1 and e2 for but-2
      yne. Energy transfer parameters (alpha = 250 cm-1) for the ethyne system were
      obtained by simulating laboratory data for N2 buffer gas, where O2 was not
      present. In simulations of C2H2 + HO when O2 is present, E1 reacts completely and
      E2 reacts almost completely, before thermalization. Radical E1 produces formic
      acid ( approximately 44%) and E2 gives glyoxal ( approximately 53%), in quite
      good agreement with experiments. For but-2-yne, pressure-dependent laboratory
      data are too scarce to obtain energy transfer parameters directly, so simulations
      were carried out for a range of values: alpha = 200-900 cm-1. Excellent agreement
      with the available experimental yields at atmospheric pressure was obtained with
      alpha = 900 cm-1. Two reaction channels are responsible for acetic acid
      formation, but one is clearly dominant. Biacetyl is produced by reactions of e1
      and, to a minor extent, e2. The peroxyl radical e2 leads to less than 8% of all
      products. Vinoxyl radical (which has been reported in experiments involving C2H2
      + HO) and products of its reactions are predicted to be negligible under
      atmospheric conditions.

PMID- 18345650
TI  - Kinetics and mechanism of proton transfer between disubstituted benzoic acids and
      carbinol base of crystal violet in chlorobenzene.
AB  - An investigation on the detailed kinetics of proton transfer between a set of di-
      and monofluoro- and chloro- (2,3-, 2,5-, 2,6-, 3,5-, 2-, and 3-) benzoic acids
      (HA) and Crystal Violet carbinol base in chlorobenzene favors a mechanism in
      terms of fast equilibrium between HA and D to form a H-bonded complex, D...HA,
      followed by rate-limiting proton transfer along the H-bond to form the colored
      ion pair DH+A- under the combined influence of monomer HA catalyst, nonreactive
      cyclic dimer (HA)2 inhibitor, and hyperacidic homoconjugated complex H(HA2)
      catalyst through a transition state with nearly 60% charge separation.

PMID- 18345651
TI  - Two-dimensional coherent double resonance electronic spectroscopy.
AB  - A new form of coherent 2D spectroscopy involving a pair of electronic resonances
      appears to provide several advantages over more established techniques. It can
      resolve congested peaks and sort them by vibrational quantum number, rotational
      quantum number, and isotopomer. The high degree of symmetry in the resulting
      spectra facilitates the ability to assign the quantum numbers and isotopomer for
      each peak. Quantitative results are demonstrated using an isotopomeric mixture of
      bromine.

PMID- 18345652
TI  - Tubular aggregates of cyclic oligothiophenes. A theoretical study.
AB  - The geometries of neutral, mono-, and dioxidized tubular aggregates of
      cyclo[8]thiophenes containing up to 5 repeating units were fully optimized at the
      MPWB1K/3-21G* level of theory. Calculated interplane distances between
      macrocycles were found to be close to 3.1 A for neutral and charged aggregates.
      The binding energies between macrocycles in neutral intermediates were in the
      range of 40-45 kcal/mol, increasing for monocations and dropping strongly for
      dicationic species due to electrostatic repulsion between polarons. It was
      established that there exists a noticeable interaction between pi-orbitals of
      individual macrocycles in tubular aggregates as follows from decreasing of the
      band gap with a number of repeating units in aggregates and the polaron
      delocalization toward tube axes in oxidized species. A polaron pair is the most
      stable dicationic state for all studied molecules according to the calculations.
      A singlet polaron pair is more stable than a triplet one. The energy difference
      between singlet and triplet states is growing smaller with the size of the
      system, becoming zero for the pentamer corresponding to a completely dissociated
      bipolaron.

PMID- 18345653
TI  - Origin of the X-Hal (Hal = Cl, Br) bond-length change in the halogen-bonded
      complexes.
AB  - The origin of the X-Hal bond-length change in the halogen bond of the X-Hal...Y
      type has been investigated at the MP2(full)/6-311++G(d,p) level of theory using a
      natural bond orbital analysis, atoms in molecules procedure, and electrostatic
      potential fitting methods. Our results have clearly shown that various theories
      explaining the nature of the hydrogen bond cannot be applied to explain the
      origin of the X-Hal bond-length change in the halogen bond. We provide a new
      explanation for this change. The elongation of the X-Hal bond length is caused by
      the electron-density transfer to the X-Hal sigma* antibonding orbital. For the
      blue-shifting halogen bond, the electron-density transfer to the X-Hal sigma*
      antibonding orbital is only of minor importance; it is the electrostatic
      attractive interaction that causes the X-Hal bond contraction.

PMID- 18345654
TI  - Spatially resolved vibrational energy transfer in molecular monolayers.
AB  - We have shown that it is possible to input heat to one location of a molecule and
      simultaneously measure its arrival in real time at two other locations, using an
      ultrafast flash-thermal conductance technique. A femtosecond laser pulse heats an
      Au layer to approximately 800 degrees C, while vibrational sum-frequency
      generation spectroscopy (SFG) monitors heat flow into self-assembled monolayers
      (SAMs) of organic thiolates. Heat flow into the SAM creates thermally induced
      disorder, which decreases the coherent SFG signal from the CH-stretching
      transitions. Recent improvements in the technique are described, including the
      use of nonresonant background-suppressed SFG. The improved apparatus was
      characterized using alkanethiolate and benzenethiolate SAMs. In the asymmetric 2
      methyl benzenethiolate SAM, SFG can simultaneously monitor CH-stretching
      transitions of both phenyl and methyl groups. The phenyl response to flash
      heating occurs at least as fast as the 1 ps time for the Au surface to heat. The
      methyl response has a faster portion similar to the phenyl response and a slower
      portion characterized by an 8 ps time constant. The faster portions are
      attributed to disordering of the methyl-substituted phenyl rings due to thermal
      excitation of the Au-S adbonds. The slower portion, seen only in the methyl SFG
      signal, is attributed to heat flow from the metal surface into the phenyl rings
      and then to the methyl groups.

PMID- 18345655
TI  - Matrix isolation infrared spectroscopic studies and density functional theory
      calculations of the MNN, (MN)2 (M = Y and La), and Y3NN molecules.
AB  - The reactions of yttrium and lanthanum with dinitrogen were reinvestigated. Laser
      ablated yttrium and lanthanum atoms were co-deposited at 4 K with dinitrogen in
      excess argon, and the low-temperature reactions of Y and La with N2 in solid
      argon were studied using infrared spectroscopy. The reaction products YNN, (YN)2,
      LaNN, and (LaN)2 were formed in the present experiments and characterized on the
      basis of 14N/15N isotopic shifts, mixed isotope splitting patterns, stepwise
      annealing, change of reagent concentration and laser energy, and comparison with
      theoretical predictions. Some assignments were made based on a previous report.
      Density functional theory calculations were performed on these systems to
      identify possible reaction products. The agreement between experimental and
      calculated vibrational frequencies, relative absorption intensities, and isotopic
      shifts of the MNN and (MN)2 (M = Y and La) molecules supports the identification
      of these molecules from the matrix infrared spectra. Plausible reaction
      mechanisms were proposed for the formation of these molecules along with
      tentative identification of the Y3NN molecule.

PMID- 18345656
TI  - The subdiffusive targeting problem.
AB  - Recent experiments in living cells have observed subdiffusive motion, where the
      mean squared displacement of a molecule grows sublinearly with time as [x (2)]
      approximately t(alpha). Motivated by these experiments, we develop a theory for
      subdiffusion-limited bimolecular enzyme kinetics. As in normal diffusion, the
      statistics of the reaction times depend on the ratio between the distance to the
      target and the reaction rate in a scale invariant manner. Contrary to some
      studies, we find no critical value of alpha and therefore no evidence to suggest
      that it has been a target of evolutionary optimization.

PMID- 18345657
TI  - Theoretical and experimental studies of the photoluminescent properties of the
      coordination polymer [Eu(DPA)(HDPA)(H2O)2].4H2O.
AB  - We report on the hydrothermal synthesis of the [Eu(DPA)(HDPA)(H(2)O)(2)].4H(2)O
      lanthanide-organic framework (where H2DPA stands for pyridine-2,6-dicarboxylic
      acid), its full structural characterization including single-crystal X-ray
      diffraction and vibrational spectroscopy studies, plus detailed investigations on
      the experimental and predicted (using the Sparkle/PM3 model) photophysical
      luminescent properties. We demonstrate that the Sparkle/PM3 model arises as a
      valid and efficient alternative to the simulation and prediction of the
      photoluminescent properties of lanthanide-organic frameworks when compared with
      methods traditionally used. Crystallographic investigations showed that the
      material is composed of neutral one-dimensional coordination polymers
      infinity(1)[Eu(DPA)(HDPA)(H(2)O)(2)] which are interconnected via a series of
      hydrogen bonding interactions involving the water molecules (both coordinated and
      located in the interstitial spaces of the structure). In particular, connections
      between bilayer arrangements of infinity(1)[Eu(DPA)(HDPA)(H(2)O)(2)] are assured
      by a centrosymmetric hexameric water cluster. The presence of this large number
      of O-H oscillators intensifies the vibronic coupling with water molecules and, as
      a consequence, increases the number of nonradiative decay pathways controlling
      the relaxation process, ultimately considerably reducing the quantum efficiency
      (eta = 12.7%). The intensity parameters (Omega(2), Omega(4), and Omega(6)) were
      first calculated by using both the X-ray and the Sparkle/PM3 structures and were
      then used to calculate the rates of energy transfer (W(ET)) and back-transfer
      (W(BT)). Intensity parameters were used to predict the radiative decay rate. The
      calculated quantum yield obtained from the X-ray and Sparkle/PM3 structures (both
      of about 12.5%) are in good agreement with the experimental value (12.0 +/- 5%).
      These results clearly attest for the efficacy of the theoretical models employed
      in all calculations and create open new interesting possibilities for the design
      in silico of novel and highly efficient lanthanide-organic frameworks.

PMID- 18345658
TI  - Mesoscopic Monte Carlo simulations of stochastic encounters between
      photoactivated rhodopsin and transducin in disc membranes.
AB  - The issue of how the molecular organization of rod outer segments (ROS) discs
      affects the initial timing of the photoresponse in vertebrates has been recently
      raised by novel structural findings that raise doubts about the classical
      scenario of monomeric rhodopsin (R) and heterotrimeric transducin (G) freely
      diffusing in the membrane milieu. In this study, we investigate this issue by
      means of mesoscopic Monte Carlo (MMC) simulations of the stochastic encounters
      between one photoactivated R and one G, explicitly taking into account the
      molecular size and the diffusion coefficient of each species as well as crowding
      effects. Three different scenarios were compared with respect to their effects on
      timing, namely, (a) the classical framework, where both G and monomeric R are
      allowed to freely diffuse in the ROS disc membrane, (b) the ideal paracrystalline
      organization of R dimers considered as a structural unit, where ordered rows
      completely cover the disc membrane patch, and (c) the scenario suggested by
      recent AFM data, where R dimers organize in differently sized rafts with varying
      local concentrations. Our simulations suggest that a similar kinetic response
      could arise from very different microscopic scenarios, thus opening new
      interpretations to the controversial recent findings. Moreover, we show that if
      high-density R packing on ROS discs is characterized by a highly ordered
      structural organization rather than unspecific aggregation, an unexpected
      favorable effect on the temporal response of early phototransduction reactions
      can occur.

PMID- 18345659
TI  - Self-assembling of phenothiazine compounds investigated by small-angle X-ray
      scattering and electron paramagnetic resonance spectroscopy.
AB  - Small-angle X-ray scattering (SAXS) and electron paramagnetic resonance (EPR)
      have been carried out to investigate the structure of the self-aggregates of two
      phenothiazine drugs, chlorpromazine (CPZ) and trifluoperazine (TFP), in aqueous
      solution. In the SAXS studies, drug solutions of 20 and 60 mM, at pH 4.0 and 7.0,
      were investigated and the best data fittings were achieved assuming several
      different particle form factors with a homogeneous electron density distribution
      in respect to the water environment. Because of the limitation of scattering
      intensity in the q range above 0.15 A(-1), precise determination of the aggregate
      shape was not possible and all of the tested models for ellipsoids, cylinders, or
      parallelepipeds fitted the experimental data equally well. The SAXS data allows
      inferring, however, that CPZ molecules might self-assemble in a basis set of an
      orthorhombic cell, remaining as nanocrystallites in solution. Such nanocrystals
      are composed of a small number of unit cells (up to 10, in c-direction), with CPZ
      aggregation numbers of 60-80. EPR spectra of 5- and 16-doxyl stearic acids bound
      to the aggregates were analyzed through simulation, and the dynamic and magnetic
      parameters were obtained. The phenothiazine concentration in EPR experiments was
      in the range of 5-60 mM. Critical aggregation concentration of TFP is lower than
      that for CPZ, consistent with a higher hydrophobicity of TFP. At acidic pH 4.0 a
      significant residual motion of the nitroxide relative to the aggregate is
      observed, and the EPR spectra and corresponding parameters are similar to those
      reported for aqueous surfactant micelles. However, at pH 6.5 a significant
      motional restriction is observed, and the nitroxide rotational correlation times
      correlate very well with those estimated for the whole aggregated particle from
      SAXS data. This implies that the aggregate is densely packed at this pH and that
      the nitroxide is tightly bound to it producing a strongly immobilized EPR
      spectrum. Besides that, at pH 6.5 the differences in motional restriction
      observed between 5- and 16-DSA are small, which is different from that observed
      for aqueous surfactant micelles.

PMID- 18345660
TI  - Conformational analysis of beta-glycosidic linkages in 13C-labeled glucobiosides
      using inter-residue scalar coupling constants.
AB  - Four beta-linked glucobioses selectively (13)C labeled at C1' or C2' have been
      prepared. The inter-residue coupling constants, J(CH), and J(CC), have been
      determined and related to the solution conformations of the disaccharides using
      Karplus-type relationships. Relying only on the experimental coupling constants,
      glycosidic linkage conformation in methyl alpha-sophoroside (methyl 2-O-beta-D
      glucopyranosyl-alpha-D-glucopyranoside), methyl alpha-laminarabioside (methyl 3-O
      beta-D-glucopyranosyl-alpha-D-glucopyranoside), and methyl alpha-cellobioside
      (methyl 4-O-beta-D-glucopyranosyl-alpha-D-glucopyranoside) were found to be close
      to those observed in the solid state (39 degrees < phi(H) < 41 degrees , -24
      degrees < psi(H) < -36 degrees ). The laminarabioside and cellobioside were found
      to have conformations that accommodate an intramolecular hydrogen bond to O5'
      that is observed in the solid state. In all compounds, the exocyclic
      hydroxymethyl groups retain a conformation close to that observed in
      unsubstituted glucose (gt/gg 1:1). Methyl alpha-gentiobioside (methyl 6-O-beta-D
      glucopyranosyl-alpha-D-glucopyranoside) shows greater flexibility at the psi
      torsion than the other disaccharides, but the population distribution around the
      C5-C6 bond is essentially unaffected by substitution. None of the O2' hydroxyl
      groups of the beta-D-glucopyranosyl residues in any of the disaccharides appear
      to be involved in inter-residue hydrogen bonding since (1)JCH, (1)JCC, and (2)JCH
      values sensitive to C2'-O2' rotamer distribution remain close to those observed
      in methyl beta-D-glucopyranoside.

PMID- 18345661
TI  - Effect of glutamate on the electrical properties of cationic solid lipid
      nanoparticles containing stearylamine and dioctadecyldimethyl ammonium bromide.
AB  - Electrical properties, including electrophoretic mobility, zeta potential, total
      surface charge density, and surface charge density resulting from primary amino
      groups, of cationic solid lipid nanoparticles (CSLNs) were investigated in the
      present study. Cationic lipids including stearylamine (SA) and
      dioctadecyldimethyl ammonium bromide (DODAB) were covered on the external cores
      of CSLNs. The influences of glutamate concentration in the medium, composition of
      cationic lipids, and surfactant species were especially analyzed. The results
      indicated that an increase in the mole ratio of SA in the cationic lipid caused
      an increase in the average diameter of CSLNs. Also, the average diameter of Span
      20-stabilized CSLNs was larger than that of Tween 80-stabilized CSLNs. The
      electrostatic traits of CSLNs were reduced as the mole ratio of SA increased, and
      the electricity of Span 20-stabilized CSLNs was weaker than that of Tween 80
      stabilized CSLNs. An increase in the glutamate concentration in the medium led to
      a decrease in electrophoretic mobility, zeta potential, and total surface charge
      density of CSLNs. As the glutamate concentration increased, surface charge
      density resulting from primary amino groups increased, and that from quaternary
      amino groups decreased as a result of the adsorption of negatively charged
      glutamate on CSLN surfaces. Ohshima's soft particle theory was adopted to
      describe the electrical behavior of CSLNs, and the deviations of zeta potential
      predicted by the Smoluchowski, Happel, and Kuwabara models were normally greater
      than 10%.

PMID- 18345662
TI  - Estimation of physicochemical properties of ionic liquids 1-alkyl-3
      methylimidazolium chloroaluminate.
AB  - The density and surface tension of ionic liquids [C(2)mim][AlCl(4)] (1-ethlyl-3
      methyl imidazolium chloroaluminate) and [C(6)mim][AlCl(4)] (1-hexyl-3
      methylimidazolium chloroaluminate) were measured in the temperature range from
      283.15 to 338.15 +/- 0.05 K. In terms of these experimental results, the
      estimation of physicochemical properties of 1-alkyl-3-methylimidazolium
      chloroaluminate ([C(n)mim][AlCl(4)], n = 1-6) was carried out. With the use of
      the parachor, the values of surface tension of the ILs were predicted. In terms
      of Glasser's theory, the standard molar entropy, lattice energy, and surface
      properties of the ILs were estimated. With the use of Kabo's method and Rebelo's
      method, the molar enthalpy of vaporization of the ILs, Delta(l)(g)H(m)(0), was
      predicted. According to the interstice model, the values of the thermal expansion
      coefficient of the ILs were also estimated. Since the magnitude order of the
      thermal expansion coefficient estimated by the model is in good agreement with
      that measured experimentally, this result means that the interstice model is
      reasonable.

PMID- 18345663
TI  - Two-photon absorption of hydrogen-bonded octupolar molecule clusters.
AB  - Charge-transfer octupolar molecules can form clusters in solution through
      intermolecular hydrogen bonds. In the present work we explore the role of such
      clustering on two-photon absorption (TPA) spectra assuming 1,3,5-triamino-2,4,6
      trinitrobenzene (TATB) as a model system. Using density functional quadratic
      response theory we examine different cluster structures of TATB dimers, trimers,
      and tetramers taken from snapshots of molecular dynamics simulations. In
      comparison with the TPA spectrum of a monomer, significant red shifts of charge
      transfer states are predicted for all chosen clusters, which mainly is the result
      of the distortion of the structures induced by the aggregation. The TPA spectra
      for dimers and trimers show strong conformation dependence, whereas they turn out
      to be more stable for tetramers. Enhancements of TPA absorption have also been
      found for clusters containing less distorted molecules connected by hydrogen
      bonds.

PMID- 18345664
TI  - Quantum mechanical/molecular mechanical simulation study of the mechanism of
      hairpin ribozyme catalysis.
AB  - The molecular mechanism of hairpin ribozyme catalysis is studied with molecular
      dynamics simulations using a combined quantum mechanical and molecular mechanical
      (QM/MM) potential with a recently developed semiempirical AM1/d-PhoT model for
      phosphoryl transfer reactions. Simulations are used to derive one- and two
      dimensional potentials of mean force to examine specific reaction paths and
      assess the feasibility of proposed general acid and base mechanisms. Density
      functional calculations of truncated active site models provide complementary
      insight to the simulation results. Key factors utilized by the hairpin ribozyme
      to enhance the rate of transphosphorylation are presented, and the roles of A38
      and G8 as general acid and base catalysts are discussed. The computational
      results are consistent with available experimental data, provide support for a
      general acid/base mechanism played by functional groups on the nucleobases, and
      offer important insight into the ability of RNA to act as a catalyst without
      explicit participation by divalent metal ions.

PMID- 18345665
TI  - Investigation of secondary structure elements by IR/UV double resonance
      spectroscopy: analysis of an isolated beta-sheet model system.
AB  - An isolated beta-sheet model system is investigated in a molecular beam
      experiment by means of mass- and isomer-selective IR/R2PI double resonance
      spectroscopy as well as ab initio and DFT calculations. As the exclusive
      intermolecular assembly, a beta-sheet motif is formed by spontaneous dimerization
      of two isolated peptide molecules. This secondary structure is produced from the
      tripeptide model Ac-Val-Tyr(Me)-NHMe without any further environment to form the
      binding motif which is analyzed by both the characteristic amide A and I
      vibrations. The experimental and theoretical investigations yield the assignment
      to an antiparallel beta-sheet model. The result of this detailed spectroscopic
      analysis on an isolated beta-sheet model indicates that there are intrinsic
      properties of a beta-sheet structure which can be formed without a solvent or a
      peptidic environment.

PMID- 18345666
TI  - (Terpyridine)copper(II)-carbon nanohorns: metallo-nanocomplexes for photoinduced
      charge separation.
AB  - New metallo-nanostructured materials of carbon nanohorns (CNHs), within the
      family of elongated carbon nanotubes, have been prepared by the coordination of
      copper(II)-2,2':6',2' '-terpyridine (Cu(II)tpy) with oxidized carbon nanohorns
      (CNHs-COOH). The resulted CNHs-COO-Cu(II)tpy metallo-nanocomplexes have been
      characterized by diverse analytical spectroscopic tools and cyclic and
      differential pulse voltammetry. Scanning transmission electron microscopy (STEM),
      dynamic light scattering (DLS), and energy dispersive X-ray spectroscopy (EDX)
      measurements have been employed to probe the morphological characteristics and
      particle-size distribution of CNHs-COO-Cu(II)tpy as well as to investigate the
      elemental composition of the metallo-nanocomplex. Steady-state and time-resolved
      fluorescence emission studies have shown efficient fluorescence quenching,
      suggesting that electron transfer occurs from the singlet excited state of
      Cu(II)tpy to CNHs. Photoexcitation of Cu(II)tpy resulted in the one-electron
      reduction of nanohorns with a simultaneous one-electron oxidation of the
      Cu(II)tpy unit (CNHs(*-)-COO-(Cu(II)tpy)*+) as revealed by transient absorption
      measurements. The charge-separated state of CNHs(*-)-COO-(Cu(II)tpy)*+ has been
      confirmed with the aid of an electron mediator, such as hexyl-viologen dication
      (HV2+) and an electron-hole shifter in polar solvents.

PMID- 18345667
TI  - In vitro characterization of the enzymes involved in TDP-D-forosamine
      biosynthesis in the spinosyn pathway of Saccharopolyspora spinosa.
AB  - Forosamine (4-dimethylamino)-2,3,4,6-tetradeoxy-beta-D-threo-hexopyranose) is a
      highly deoxygenated sugar component of several important natural products,
      including the potent yet environmentally benign insecticide spinosyns. To study D
      forosamine biosynthesis, the five genes (spnO, N, Q, R, and S) from the spinosyn
      gene cluster thought to be involved in the conversion of TDP-4-keto-6-deoxy-D
      glucose to TDP-D-forosamine were cloned and heterologously expressed, and the
      corresponding proteins were purified and their activities examined in vitro.
      Previous work demonstrated that SpnQ functions as a pyridoxamine 5'-monophosphate
      (PMP)-dependent 3-dehydrase which, in the presence of the cellular reductase
      pairs ferredoxin/ferredoxin reductase or flavodoxin/flavodoxin reductase,
      catalyzes C-3 deoxygenation of TDP-4-keto-2,6-dideoxy-D-glucose. It was also
      established that SpnR functions as a transaminase which converts the SpnQ
      product, TDP-4-keto-2,3,6-trideoxy-D-glucose, to TDP-4-amino-2,3,4,6-tetradeoxy-D
      glucose. The results presented here provide a full account of the
      characterization of SpnR and SpnQ and reveal that SpnO and SpnN functions as a
      2,3-dehydrase and a 3-ketoreductase, respectively. These two enzymes act
      sequentially to catalyze C-2 deoxygenation of TDP-4-keto-6-deoxy-D-glucose to
      form the SpnQ substrate, TDP-4-keto-2,6-dideoxy-D-glucose. Evidence has also been
      obtained to show that SpnS functions as the 4-dimethyltransferase that converts
      the SpnR product to TDP-D-forosamine. Thus, the biochemical functions of the five
      enzymes involved in TDP-D-forosamine formation have now been fully elucidated.
      The steady-state kinetic parameters for the SpnQ-catalyzed reaction have been
      determined, and the substrate specificities of SpnQ and SpnR have been explored.
      The implications of this work for natural product glycodiversification and
      comparative mechanistic analysis of SpnQ and related NDP-sugar 3-dehydrases E1
      and ColD are discussed.

PMID- 18345668
TI  - Evidence for concerted pathways in ion-pairing coupled electron transfers.
AB  - Ion-pairing with electro-inactive metal ions may change drastically the
      thermodynamic and kinetic reactivity of electron transfer in chemical and
      biochemical processes. Besides the classical stepwise pathways (electron-transfer
      first, followed by ion-pairing or vice versa), ion-pairing may also occur
      concertedly with electron transfer. The latter pathway avoids high-energy
      intermediates but a key issue is that of the kinetic price to pay to benefit from
      this thermodynamic advantage. A model is proposed leading to activation/driving
      force relationships characterizing such concerted associative electron transfers
      for intermolecular and intramolecular homogeneous reactions and for
      electrochemical reactions. Contrary to previous assertions, the driving force of
      the reaction (defined as the opposite of the reaction standard free energy), as
      well as the intrinsic barrier, does not depend on the concentration of the ion
      pairing agent, which simply plays the role of one of the reactants. Besides
      solvent and intramolecular reorganization, the energy of the bond being formed is
      the main component of the intrinsic barrier. Application of these considerations
      to reactions reported in recent literature illustrates how concerted ion-pairing
      electron-transfer reactions can be diagnosed and how competition between stepwise
      and concerted pathways can be analyzed. It provided the first experimental
      evidence of the viability of concerted ion-pairing electron-transfer reactions.

PMID- 18345669
TI  - Computer simulation study of the structural stability and materials properties of
      DNA-intercalated layered double hydroxides.
AB  - The intercalation of DNA into layered double hydroxides (LDHs) has various
      applications, including drug delivery for gene therapy and origins of life
      studies. The nanoscale dimensions of the interlayer region make the exact
      conformation of the intercalated DNA difficult to elucidate experimentally. We
      use molecular dynamics techniques, performed on high performance supercomputing
      grids, to carry out large-scale simulations of double stranded, linear and
      plasmid DNA up to 480 base pairs in length intercalated within a magnesium
      aluminum LDH. Currently only limited experimental data have been reported for
      these systems. Our models are found to be in agreement with experimental
      observations, according to which hydration is a crucial factor in determining the
      structural stability of DNA. Phosphate backbone groups are found to align with
      aluminum lattice positions. At elevated temperatures and pressures, relevant to
      origins of life studies which maintain that the earliest life forms originated
      around deep ocean hydrothermal vents, the structural stability of LDH
      intercalated DNA is substantially enhanced as compared to DNA in bulk water. We
      also discuss how the materials properties of the LDH are modified due to DNA
      intercalation.

PMID- 18345670
TI  - Fluorinated bis(phenoxyketimine)titanium complexes for the living, isoselective
      polymerization of propylene: multiblock isotactic polypropylene copolymers via
      sequential monomer addition.
AB  - A series of bis(phenoxyketimine)titanium dichloride complexes were synthesized
      and evaluated as catalysts for living, isoselective propylene polymerization upon
      activation with methylaluminoxane (MAO). Catalysts bearing phenoxyketimine
      ligands with different substituents at the ortho and para positions of the
      phenolate ring and substituents at the ketimine carbon were investigated. The
      identity of the ketimine substituent had the largest effect on the activity and
      isoselectivity of propylene polymerization. Complex 12/MAO promoted the living,
      isoselective polymerization of propylene ([m4] = 0.73, alpha = 0.94). This
      catalyst system was used for the synthesis of a number of block copolymers
      featuring isotactic polypropylene semicrystalline blocks and poly(ethylene-co
      propylene) amorphous blocks. Several triblock samples with varying block lengths,
      a pentablock, and a heptablock copolymer were synthesized. Mechanical testing has
      revealed that each is elastomeric with elongations at break between approximately
      790-1000%.

PMID- 18345671
TI  - How deep is the potential well confining a protein in a specific conformation? A
      single-molecule study on temperature dependence of conformational change between
      5 and 18 K.
AB  - The fluorescence excitation spectrum of a single chromophore molecule in a
      photosynthetic pigment-protein complex is known to change in time at liquid
      helium temperature. The spectral change reflects a conformational change of the
      protein to which the chromophore binds. This work follows the temporal behavior
      of the spectrum of a single chromophore in the temperature range between 5 adn 18
      K. The temperature dependence reveals two types of conformational change of the
      protein, i.e., thermally activated motions over a potential barrier of ca. 0.1
      kJ/mol and temperature-independent motions of tunneling of a proton.

PMID- 18345672
TI  - Single-conformation ultraviolet and infrared spectroscopy of model synthetic
      foldamers: beta-peptides Ac-beta3-hPhe-NHMe and Ac-beta3-hTyr-NHMe.
AB  - The conformational preferences and infrared and ultraviolet spectral signatures
      of two model beta-peptides, Ac-beta3-hPhe-NHMe (1) and Ac-beta3-hTyr-NHMe (2),
      have been explored under jet-cooled, isolated molecule conditions. The mass
      resolved, resonant two-photon ionization spectra of the two molecules were
      recorded in the region of the S0-S1 origin of the phenyl or phenol ring
      substituents, respectively. UV-UV hole-burning spectroscopy was used to determine
      that two conformations of 1 are present, with the transitions due to conformer A,
      with S0-S1 origin at 34431 cm(-1), being almost 20 times larger than those due to
      conformer B, with S0-S1 origin at 34404 cm(-1). Only one conformation of 2 was
      observed. Resonant ion-dip infrared spectroscopy provided single-conformation
      infrared spectra in the 3300-3700 cm(-1) region. The spectra of conformer A of
      both molecules have H-bonded and free amide NH stretch infrared transitions at
      3400 and 3488 cm(-1), respectively, while conformer B of 1 possesses bands at
      3417 and 3454 cm(-1). For comparison with experiment, full optimizations of all
      low-lying minima of 1 were carried out at the DFT B3LYP/6-31+G* and RIMP2/aug-cc
      pVDZ levels of theory, and single point MP2/6-31+G* calculations at the DFT
      geometries. On the basis of the comparison with previous studies in solution and
      the calculated results, conformer A of 1 and 2 were assigned to a C6 conformer,
      while conformer B of 1 was assigned to a unique C8 structure with a weak
      intramolecular H-bond. The reasons for the preference for C6 over C8 structures
      and the presence of only two conformations in the jet-cooled spectrum are
      discussed in light of the predictions from calculations.

PMID- 18345673
TI  - Single-conformation ultraviolet and infrared spectroscopy of model synthetic
      foldamers: beta-peptides Ac-beta3-hPhe-beta3-hAla-NHMe and Ac-beta3-hAla-beta3
      hPhe-NHMe.
AB  - The conformational preferences and infrared and ultraviolet spectral signatures
      of two model beta-peptides, Ac-beta3-hPhe-beta3-hAla-NHMe (1) and Ac-beta3-hAla
      beta3-hPhe-NHMe (2), have been explored under jet-cooled, isolated-molecule
      conditions. The mass-resolved, resonant two-photon ionization spectra of the two
      molecules were recorded in the region of the S0-S1 origin of the phenyl
      substituents (37,200-37,800 cm(-1)). UV-UV hole-burning spectroscopy was used to
      determine the ultraviolet spectral signatures of five conformational isomers of
      both 1 and 2. Transitions due to two conformers (labeled A and B) dominate the
      R2PI spectra of each molecule, while the other three are minor conformers (C-E)
      with transitions a factor of 3-5 smaller. Resonant ion-dip infrared spectroscopy
      was used to obtain single-conformation infrared spectra in the 3300-3700 cm(-1)
      region. The infrared spectra showed patterns of NH stretch transitions
      characteristic of the number and type of intramolecular H-bonds present in the
      beta-peptide backbone. For comparison with experiment, full optimizations of low
      lying minima of both molecules were carried out at DFT B3LYP/6-31+G*, followed by
      single point MP2/6-31+G* and selected MP2/aug-cc-pVDZ calculations at the DFT
      optimized geometries. Calculated harmonic vibrational frequencies and infrared
      intensities for the amide NH stretch vibrations were used to determine the beta
      peptide backbone structures for nine of the ten observed conformers. Conformers
      1B, 1D, and 2A were assigned to double ring structures containing two C6 H-bonded
      rings (C6a/C6a), conformers 1A and 2B are C10 single H-bonded rings, conformers
      1C and 2D are double ring structures composed of two C8 H-bonded rings (C8/C8),
      and conformers 1E and 2E are double ring/double acceptor structures in which two
      NH groups H-bond to the same C=O group, thereby weakening both H-bonds. Both 1E
      and 2E are tentatively assigned to C6/C8 double ring/double acceptor structures,
      although C8/C12 structures cannot be ruled out unequivocally. Finally, no firm
      conformational assignment has been made for conformer 2C whose unusual infrared
      spectrum contains one very strong H-bond with NH stretch frequency at 3309 cm(
      1), a second H-bonded NH stretch fundamental of more typical value (3399 cm(-1)),
      and a third fundamental at 3440 cm(-1), below that typical of a branched-chain
      free NH. The single conformation spectra provide characteristic wavenumber ranges
      for the amide NH stretch fundamentals ascribed to C6 (3378-3415 cm(-1)), C8 (3339
      3369 cm(-1)), and C10 (3381-3390 cm(-1)) H-bonded rings.

PMID- 18345674
TI  - A homochiral nanotubular crystalline framework of metallomacrocycles for
      enantioselective recognition and separation.
AB  - A highly ordered homochiral nanotubular crystalline framework was assembled from
      a hexameric Zn6L6metallaycle that was built from metallosalen ZnL units (H2L =
      (R,R)-(-)-N,N'-Bis(3-tert-butyl-5-(4- pyridyl) salicylidene)-1,2
      diaminocyclohexane) by the complementary coordination of the pyridyl groups to
      the metal centers. Chiral channels and hydrophobic functionality presented by
      this structure make it an excellent host to recognize and separate racemic
      alcohols with high enantioselectivity (up to 99.5%). The crystalline solid can be
      easily recycled and reused five times without loss of crystallinity and
      enantioselectivity.

PMID- 18345675
TI  - Regioselective beta-metalation of meso-phosphanylporphyrins. Structure and
      optical properties of porphyrin dimers linked by peripherally fused
      phosphametallacycles.
AB  - meso-Diphenylphosphanylporphyrins were successfully prepared via Pd-catalyzed C-P
      cross-coupling reaction of the corresponding meso-iodoporphyrins with
      diphenylphosphane. The meso- phosphanylporphyrins underwent regioselective
      metalation at the beta carbon to produce novel classes of porphyrin dimers linked
      by peripherally fused phosphametallacycles. A Pd-mononucler complex was
      structurally characterized by X-ray crystallography, which revealed a flat
      structure of the Pd-linked porphyrin pi systems. Both experimental and
      theoretical results demonstrate that the orbital interaction between the pyrrolic
      ppi orbitals and the metal dpi orbital affects optical and electrochemical
      properties of the metal-linked coplanar porphyrin dimers.

PMID- 18345676
TI  - A new catalytically active colloidal platinum nanocatalyst: the multiarmed
      nanostar single crystal.
AB  - Nanocatalysts that possess large amounts of atoms on sharp corners and edges and
      high indexed sites are known to be more catalytically active. We report here on a
      novel yet simple method to synthesize in large yields a very active platinum
      nanocatalyst; the multiarmed nanostar single crystal. We utilize a seed mediated
      method using tetrahedral nanoparticles that are also synthesized by a new and
      simple technique. High-resolution TEM shows that the nanostar has many arms,
      varying from a few to over 30, whereby even the largest ones are found to have
      single-crystal structures. This strongly suggests that they are formed by a
      growth mechanism of the seed crystals and not by the aggregation of seed
      crystals, which should produce twinning planes. Due to the reduction reaction of
      ferrricyanide by thiosulfate, the nanostars are found to have an activation
      energy, which is nearly 60% of that of the tetrahedral seeds themselves, both
      having the same PVP capping agent. This is undoubtedly due to the multiarms with
      edges, corners, and the presence of high indexed facets in the nanostar catalyst.

PMID- 18345677
TI  - Type II isopentenyl diphosphate isomerase: irreversible inactivation by covalent
      modification of flavin.
AB  - Isopentenyl diphosphate isomerase (IDI) catalyzes the interconversion of
      isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), the basic
      building blocks of isoprenoid molecules. Two structurally unrelated classes of
      IDI are known. Type I IPP isomerase (IDI-1) utilizes a divalent metal in a
      protonation-deprotonation reaction; whereas, the type II enzyme (IDI-2) requires
      reduced flavin. Epoxy, diene, and fluorinated substrate analogues, irreversible
      inhibitors of IDI-1, were analyzed as mechanistic probes for IDI-2. 3,4-Oxido-3
      methyl-1-butyl diphosphate (eIPP), 3-methylene-4-penten-1-yl diphosphate (vIPP),
      and 3-(fluoromethyl)-3-buten-1-yl diphosphate (fmIPP) inactivate IDI-2 through
      formation of covalent adducts with the reduced flavin. UV-visible spectra of the
      inactivated complexes are consistent with modification of the isoalloxazine ring
      at position N5. vIPP and fmIPP are also alternate substrates with isomerization
      competing with alkylation of the flavin cofactor. (Z)-3-(Fluoromethyl)-2-buten-1
      yl diphosphate ((Z)-fmDMAPP) and (Z)-3-(difluoromethyl)-2-buten-1-yl diphosphate
      ((Z)-dfmDMAPP) are alternate substrates, which are isomerized to the
      corresponding IPP derivatives. The rates of isomerization of fmIPP and (Z)
      fmDMAPP are approximately 50-fold less than IPP and DMAPP, respectively. dfmIPP
      is not an irreversible inhibitor. These studies indicate that the irreversible
      inhibitors inactivate the reduced flavin required for catalysis by electrophilic
      alkylation and are consistent with a protonation-deprotonation mechanism for the
      isomerization catalyzed by IDI-2.

PMID- 18345678
TI  - Therapeutic target metabolism observed using hyperpolarized 15N choline.
AB  - Choline is a precursor of cellular phospholipid metabolism that provides Magnetic
      Resonance (MR) and Positron Emission Tomography (PET) biomarkers for cancer
      detection and response assessment. Employing Dynamic Nuclear Polarization we show
      that the MR signal of 15N in choline can be enhanced by at least 4 orders of
      magnitude with a relaxation time of ca. 4 min, providing a method to observe the
      action of choline kinase, an important target for novel cancer therapeutics.

PMID- 18345679
TI  - Palladium-catalyzed aromatic esterification of aldehydes with organoboronic acids
      and molecular oxygen.
AB  - A palladium-catalyzed aromatic esterification reaction of aldehydes with
      arylboronic acids under an air atmosphere was achieved. This reaction tolerates
      many functional groups and provides aryl benzoate derivatives with yields ranging
      from moderate to good. Dioxygen takes part in the reaction and is crucial for
      this transformation.

PMID- 18345680
TI  - One-pot three-component synthesis of alpha-iminonitriles by IBX/TBAB-mediated
      oxidative Strecker reaction.
AB  - The reaction of aldehydes, amines, and TMSCN in the presence of 2-iodoxybenzoic
      acid (IBX) and tetrabutylammonium bromide (TBAB) afforded alpha-iminonitriles in
      good to excellent yields under mild conditions. The presence of TBAB is essential
      for this transformation. The methodology was applied to a two-step synthesis of
      indolizidine via a microwave-assisted intramolecular cycloaddition of alpha
      iminonitrile.

PMID- 18345681
TI  - Escherichia coli glucuronylsynthase: an engineered enzyme for the synthesis of
      beta-glucuronides.
AB  - The glycosynthase derived from E. coli beta-glucuronidase catalyzes the
      glucuronylation of a range of primary, secondary, and aryl alcohols with moderate
      to excellent yields. The procedure provides an efficient, stereoselective, and
      scalable single-step synthesis of beta-glucuronides under mild conditions.

PMID- 18345682
TI  - Sc3+-catalyzed aldol-type additions of N-benzoylcyclopropanecarboxamides via
      iodide-mediated ring-opening: stereoselective synthesis of gamma-lactams.
AB  - A new catalytic aldol-type addition of cyclopropanecarboximides to aldehydes via
      iodide-mediated ring-opening is presented. The reaction was found to be catalyzed
      at 0 degrees C using either a Sc(OTf)3/NaI system or ScI3. Stereoselective
      formation of alpha,alpha-disubstituted enolates occurred in situ. gamma-Lactams
      bearing alpha-carbonyl quaternary stereocenters were obtained in 97-57% yield and
      dr = 90:10-80:20 after ring closure.

PMID- 18345683
TI  - Allenyl azide cycloaddition chemistry. photochemical initiation and CuI mediation
      leads to improved regioselectivity.
AB  - Irradiation of 2-(3-alkenyl)allenylphenyl azides in the presence of excess CuI
      furnished functionalized 2,3-cyclopentenylindoles in good yield with only trace
      amounts of competitive C-N-bonded regioisomeric products. These results represent
      a significant departure from the modest-to-nonexistent regioselectivity that
      attended thermal cyclization of these allenyl azide substrates.

PMID- 18345685
TI  - Synthesis and testing of 2-deoxy-2,2-dihaloglycosides as mechanism-based
      inhibitors of alpha-glycosidases.
AB  - The synthesis of a series of 2-deoxy-2,2-dihaloglycosyl halides as potential
      alpha-glycosidase inactivators has been achieved via the halogenation of
      protected 2-fluoroglycal precursors. Direct chlorination of per-O-acetylated 2
      fluoro-d-glucal and 2-fluoromaltal followed by basic deprotection yielded the
      corresponding 2-chloro-2-deoxy-2-fluoroglycosyl chlorides. Reaction of the per-O
      acetylated 2-fluoroglycals with acetyl hypofluorite or Selectfluor yielded the 2
      deoxy-2,2-difluoroglycosyl derivatives, which were converted to their alpha
      chlorides using thionyl chloride and deprotected under basic conditions.
      Trinitrophenyl glycosides of the 2-deoxy-2,2-difluoro mono- and disaccharides
      were synthesized by arylation of the hemiacetals with picryl fluoride, then
      deprotected with HCl in methanol. All three monosaccharide derivatives caused
      active site-directed, time-dependent inactivation of yeast alpha-glucosidase via
      the trapping of covalent glycosyl-enzyme intermediates, and kinetic parameters
      for inactivation by each compound were determined. Surprisingly neither of the 2
      deoxy-2,2-dihalomaltosyl chlorides caused time-dependent inactivation of human
      pancreatic alpha-amylase, despite the fact that the trinitrophenyl 2-deoxy-2,2
      difluoromaltoside functioned in that mode. The trinitrophenyl glycosides appear
      to be approximately 1000-fold more reactive than the corresponding chlorides in
      the enzyme active sites.

PMID- 18345686
TI  - Synthesis of cyclic peroxides containing the Si-gem-bisperoxide fragment.
      1,2,4,5,7,8-Hexaoxa-3-silonanes as a new class of peroxides.
AB  - A method was developed for the synthesis of the previously unknown class of
      organic peroxides, 1,2,4,5,7,8-hexaoxa-3-silonanes, based on the reaction of
      dialkyldichlorosilanes with 1,1'-dihydroperoxyperoxides. 1,2,4,5,7,8-Hexaoxa-3
      silonanes are rather stable under ambient conditions and were characterized by
      NMR spectroscopy, X-ray diffraction, and elemental analysis. Their yields are in
      a range of 59-96%. The attempts were made to prepare 1,2,4,5-tetraoxa-3-silinanes
      by the reaction of dialkyldichlorosilanes with gem-bishydroperoxides. 1,2,4,5
      Tetraoxa-3-silinanes were detected by NMR spectroscopy; these compounds rapidly
      decompose upon isolation.

PMID- 18345687
TI  - Decarboxylative isomerization of N-Acyl-2-oxazolidinones to 2-oxazolines.
AB  - N-Acyl-2-oxazolidinones are ring-opened by lithium iodide and decarboxylated in
      the presence of a mild proton source. Further reaction with an amine base
      provides 2-oxazolines. The transformation is general for oxazolidinones
      unsubstituted in the 5 position and occurs under mild conditions (25-50 degrees
      C). These results complement the existing methods for this transformation by
      allowing lower temperatures and/or avoiding metal catalysts.

PMID- 18345688
TI  - Biomimetic total synthesis of malbrancheamide and malbrancheamide B.
AB  - The biomimetic total syntheses of both malbrancheamide and malbrancheamide B are
      reported. The synthesis of the two monochloro species enabled the structure of
      malbrancheamide B to be unambiguously assigned. The syntheses each feature an
      intramolecular Diels-Alder reaction of a 5-hydroxypyrazin-2(1H)-one to construct
      the bicyclo[2.2.2]diazaoctane core, which has also been proposed as the
      biosynthetic route to these compounds.

PMID- 18345689
TI  - Detection of multiphosphorylated peptides in LC-MS/MS analysis under low pH
      conditions.
AB  - An improved method of detection of multiphosphorylated peptides by RPLC-MS/MS
      analysis under low pH conditions (pH approximately 1.7, 3% formic acid) is
      demonstrated for the model phosphoproteins, bovine alpha- and beta-casein.
      Changes in the pH conditions from normal (pH approximately 3.0, 0.1% formic acid)
      to low (pH approximately 1.7, 3% formic acid) significantly improved the
      detection limit of multiphosphorylated peptides carrying negative (-) solution
      charge states. In particular, bovine beta-casein tetraphosphorylated peptide, was
      detected with a loading amount of only 50 fmol of trypsin-digested bovine beta
      casein under low pH conditions, which is 200 times lower than necessary to detect
      the peptide under normal pH conditions. In order to understand the low pH effect,
      various loading amounts of trypsin-digested bovine alpha- and beta-caseins were
      analyzed by RPLC-MS/MS analyses under two different pH conditions. The question
      of whether the low pH condition improves the detection of multiphosphorylated
      peptides by increasing ionization efficiencies could not be proven in this study
      because synthetic multiphosphorylated peptides could not be easily obtained by
      peptide synthesis. Interestingly, increased hydrophilicity resulting from
      multiple phosphorylation events is shown to negatively affect the peptide
      retention on reversed-phase column material. It was also demonstrated that the
      low pH condition could effectively enhance the retention of multiphosphorylated
      peptides on reversed-phase column material. The usefulness of low pH RPLC
      analysis was tested using an actual phosphopeptide-enriched sample prepared from
      mouse brain tissues. Previously, low pH solvents have been used in SCX
      fractionation and TiO2 enrichment processes to selectively enrich phosphopeptides
      during the phosphopeptide enrichment procedure, but the improved detection of
      multiphosphorylated peptides in RPLC-MS/MS analysis under low pH conditions has
      not been reported before (Ballif, B. A.; Villen, J.; Beausoleil, S. A.; Schwartz,
      D.; Gygi, S. P. Mol. Cell. Proteomics 2004, 3, 1093-1101. Villen, J.; Beausoleil,
      S. A.; Gerber, S. A.; Gygi, S. P. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 1488
      1493. Schlosser, A.; Vanselow, J. T.; Kramer, A. Anal. Chem. 2005, 77, 5243
      5250.).

PMID- 18345690
TI  - Near-infrared spectropolarimetry based on acousto-optical tunable filters.
AB  - A new approach to near-infrared (NIR) spectropolarimetry is described, in which
      the properties of a noncollinear acousto-optical tunable filter (AOTF) made of an
      anisotropic crystal of TeO2 is employed to produce a novel instrument that
      precludes or reduces significantly the use of mechanical parts and simplifies the
      acquisition of optical rotation spectra of absorbing species in the NIR region.
      In essence, the instrument is based on the measurement of the relative beam
      intensities produced when a 45 degrees plane polarized beam of radiation passes
      through a sample cell and is directed to the entrance window of the AOTF. Because
      of the crystal anisotropy, two planar and orthogonally polarized beams will leave
      the AOTF, angularly split from the nondiffracted beam, after the acousto-optical
      interaction has occurred. If an optically nonactive sample is present in the
      cell, equal intensities for both diffracted beams should be observed. On the
      other hand, the presence of an optically active sample will cause the
      polarization plane to rotate and a consequent difference in the intensities of
      the AOTF diffracted beams will be registered as a function of the optical
      activity of the sample. The instrument has been evaluated with aqueous solutions
      of sucrose, glucose, and fructose and for three forms of camphor (d, l, dl).

PMID- 18345691
TI  - Organochlorine pesticides by LC-MS.
AB  - Contamination of water resources by organochlorine pesticides (OCPs) continues to
      receive widespread attention because of the increasing concern regarding their
      high persistence and bioaccumulation. These organic pollutants are not amenable
      by liquid chromatography (LC) coupled to atmospheric pressure ionization-mass
      spectrometry, which represents the method of choice for the characterization of
      pesticide residues in water. Gas chromatography-mass spectrometry provides
      excellent response for OCPs, but it falls short when complex, multiresidue
      analyses are required. As recently demonstrated, an efficient EI-based LC-MS
      interface can generate very good spectra for an extremely wide range of small
      medium molecular weight molecules of different polarity and can represent a valid
      tool in solving the analytical challenge of analyzing OCPs by LC-MS. Based on
      this assumption, we present a new approach for the determination of 12 OCPs in
      water samples. The method requires a solid-phase extraction preconcentration step
      followed by nanoscale liquid chromatography coupled to a direct-electron
      ionization direct interface (Direct-EI). Direct-EI is a miniaturized interface
      for efficiently coupling a liquid chromatograph with an EI mass spectrometer. The
      capability to acquire high-quality EI spectra in a wide range of concentrations,
      and to operate in selected ion monitoring mode during analyses, allowed a precise
      quantification of the OCPs. Without sample injection enrichment, limits of
      detection of the method span from 0.044 to 0.33 microg/L, corresponding to an
      instrumental detection limit of 120-850 pg. In addition, a careful evaluation of
      the matrix effect showed that the response of the Direct-EI interface was never
      affected by sample interferences. From our knowledge, the proposed method
      represents the first application of LC-MS in the analysis of organochlorine
      pesticides.

PMID- 18345692
TI  - Tunable photochromism of spirobenzopyran via selective metal ion coordination: an
      efficient visual and ratioing fluorescent probe for divalent copper ion.
AB  - In the present paper, a new spirobenzopyran derivative was synthesized and
      applied in simultaneously colorimetric and fluorescence ratiometric detections of
      Cu2+. In contrast to the virtually photochromic character of the common
      spirobenzopyrans in most organic solvents, this spirobenzopyran is colorless in
      organic aqueous solution even irradiating by ultraviolet light. The formation of
      red merocyanine in an ethanol-aqueous solution is only induced by Cu2+
      coordination. Furthermore, the closed form of the spirobenzopyran is highly
      fluorescent. Upon complexation with Cu2+, it displays not only decreasing in the
      initial fluorescence emission band but also appearing in a new emission at long
      wavelength. Thus, the Cu2+ quantitative measure can be achieved by fluorescence
      ratiometry. With the optimum conditions described, the Cu2+ concentration can be
      determined from 5.13 x 10(-7) M to 3.81 x 10(-4) with a detection limit of 1.06 x
      10(-7) M. Both the color and the fluorescence changes of the spirobenzopyran are
      extremely specific for Cu2+ over biologically relevant substrates, which meet the
      selectivity requirements for biomedical application. Serum divalent copper values
      were determined using this spirobenzopyran, which fell into the normal range of
      the content reported in the literature and were in good agreement with those
      obtained by atomic absorption spectroscopy. The combined data from fluorescence
      titrations and 1H NMR measurements indicate that the new emission of the
      spirobenzopyran generated by Cu2+ is the result of the metal-induced ring opening
      and conformation restriction by Cu2+ liganding with the opened merocyanine form
      and the subsequent reduction of the intramolecular charge transfer of the
      merocyanine.

PMID- 18345693
TI  - Atmospheric pressure chemical ionization source. 1. Ionization of compounds in
      the gas phase.
AB  - A novel chemical ionization source for organic mass spectrometry is introduced.
      This new source uses a glow discharge in the flowing afterglow mode for the
      generation of excited species and ions. The direct-current gas discharge is
      operated in helium at atmospheric pressure; typical operating voltages and
      currents are around 500 V and 25 mA, respectively. The species generated by this
      atmospheric pressure glow discharge are mixed with ambient air to generate
      reagent ions (mostly ionized water clusters and NO+), which are then used for the
      ionization of gaseous organic compounds. A wide variety of substances, both polar
      and nonpolar, can be ionized. The resulting mass spectra generally show the
      parent molecular ion (M+ or MH+) with little or no fragmentation. Proton transfer
      from ionized water clusters has been identified as the main ionization pathway.
      However, the presence of radical molecular ions (M+) for some compounds indicates
      that other ionization mechanisms are also involved. The analytical capabilities
      of this source were evaluated with a time-of-flight mass spectrometer, and
      preliminary characterization shows very good stability, linearity, and
      sensitivity. Limits of detection in the single to tens of femtomole range are
      reported for selected compounds.

PMID- 18345694
TI  - Atmospheric pressure chemical ionization source. 2. Desorption-ionization for the
      direct analysis of solid compounds.
AB  - The flowing afterglow-atmospheric pressure glow discharge (APGD) ionization
      source described in part 1 of this study (in this issue) is applied to the direct
      analysis of condensed-phase samples. When either liquids or solids are exposed to
      the ionizing beam of the APGD, strong signals for the molecular ions of
      substances present on their surfaces can be detected without compromising the
      integrity of the solid sample structure or sample substrate. As was observed for
      gas-phase compounds in part 1 of this study, both polar and nonpolar substances
      can be ionized and detected by mass spectrometry. The parent molecular ion (or
      its protonated counterpart) is usually the main spectral feature, with little or
      no fragmentation in evidence. Preliminary quantitative results show that this
      approach offers very good sensitivity (detection limits in the picogram regime
      are reported for several test compounds in part 1 of this study) and linear
      response to the analyte concentration. Examples of the application of this
      strategy to the analysis of real-world samples, such as the direct analysis of
      pharmaceutical compounds or foods is provided. The ability of this source to
      perform spatially resolved analysis is also demonstrated. Preliminary studies of
      the mechanisms of the reactions involved are described.

PMID- 18345695
TI  - Bile salt-induced vesicle-to-micelle transition in catanionic surfactant systems:
      steric and electrostatic interactions.
AB  - The vesicle-to-micelle transition (VMT) was realized in catanionic surfactant
      systems by the addition of two kinds of bile salts, sodium cholate (SC) and
      sodium deoxycholate (SDC). It was found that steric interaction between the bile
      salt and catanionic surfactant plays an important role in catanionic surfactant
      systems that are usually thought to be dominated by electrostatic interaction.
      The facial amphiphilic structure and large occupied area of the bile salt are
      crucial to the enlargement of the average surfactant headgroup area and result in
      the VMT. Moreover, bile salts can also induce a macroscopic phase transition.
      Freeze-fracture transmission electron microscopy, dynamic light scattering,
      isothermal titration calorimetry, and absorbance measurements were used to follow
      the VMT process.

PMID- 18345696
TI  - Quasistatic computer simulation study of the shear behavior of Bi- and trilayer
      water films confined between model hydrophilic surfaces.
AB  - In this paper, our previous simulations of the shear behavior of confined water
      monolayers (Pertsin, A.; Grunze, M. Langmuir 2008, 24, 135) are extended to water
      films two and three monolayers thick. The shear response of the films is studied
      in the quasistatic regime corresponding to the infinitely low shear rate. In
      certain ranges of wall-to-wall separations, bilayer films are found to be capable
      of sustaining shear stress, as is characteristic of solids, while remaining
      fluidlike in respect of the lateral order and molecular mobility. The relation
      between the solidlike and fluidlike properties of the films is dependent on the
      relative alignment of the walls and on the period of the wall lattice. The films
      become more fluid when the walls are moved out of alignment and when the wall
      lattice is uniformly compressed or stretched with respect to the "optimum"
      lattice that favors crystal-like packing. Trilayer films do not sustain shear
      stress in the whole range of wall-to-wall separations where these films are
      formed.

PMID- 18345697
TI  - Gene electrotransfer into murine skeletal muscle: a systematic analysis of
      parameters for long-term gene expression.
AB  - Skeletal muscle is an attractive target tissue for delivery of therapeutic genes,
      since it is well vascularized, easily accessible, and has a high capacity for
      protein synthesis. For efficient transfection in skeletal muscle, several
      protocols have been described, including delivery of low voltage electric pulses
      and a combination of high and low voltage electric pulses. The aim of this study
      was to determine the influence of different parameters of electrotransfection on
      short-term and long-term transfection efficiency in murine skeletal muscle, and
      to evaluate histological changes in the treated tissue. Different parameters of
      electric pulses, different time lags between plasmid DNA injection and
      application of electric pulses, and different doses of plasmid DNA were tested
      for electrotransfection of tibialis cranialis muscle of C57Bl/6 mice using DNA
      plasmid encoding green fluorescent protein (GFP). Transfection efficiency was
      assessed on frozen tissue sections one week after electrotransfection using a
      fluorescence microscope and also noninvasively, followed by an in vivo imaging
      system using a fluorescence stereo microscope over a period of several months.
      Histological changes in muscle were evaluated immediately or several months after
      electrotransfection by determining infiltration of inflammatory mononuclear cells
      and presence of necrotic muscle fibers. The most efficient electrotransfection
      into skeletal muscle of C57Bl/6 mice in our experiments was achieved when one
      high voltage (HV) and four low voltage (LV) electric pulses were applied 5
      seconds after the injection of 30 microg of plasmid DNA. This protocol resulted
      in the highest short-term as well as long-term transfection. The fluorescence
      intensity of the transfected area declined after 2-3 weeks, but GFP fluorescence
      was still detectable 18 months after electrotransfection. Extensive inflammatory
      mononuclear cell infiltration was observed immediately after the
      electrotransfection procedure using the described parameters, but no necrosis or
      late tissue damage was observed. This study showed that electric pulse
      parameters, time lag between the injection of DNA and application of electric
      pulses, and dose of plasmid DNA affected the duration of transgene expression in
      murine skeletal muscle. Therefore, transgene expression in muscle can be
      controlled by appropriate selection of electrotransfection protocol.

PMID- 18345698
TI  - Low generation polypropylenimine dendrimer graft beta-cyclodextrin: an efficient
      vector for gene delivery system.
AB  - The purpose of this study was to evaluate the characterization of a new cationic
      vector. Low generation polypropylenimine (DAB-8) was conjugated to beta
      cyclodextrin (beta-CyD), and the chemical characters of the vector were
      investigated and confirmed by 1H NMR, FT-IR, TGA, TEM, particle size, and zeta
      potential assay. The biological property was identified by MTT assay and gene
      transfer efficiency was performed in cell lines. The results showed that the new
      vector had low cytotoxicity and high transfection efficiency in vitro. This
      suggested that beta-CyD-DAB-8 has a potential ability to act as a non-viral
      vector in gene delivery.

PMID- 18345699
TI  - Long-lasting in vivo gene silencing by electrotransfer of shRNA expressing
      plasmid.
AB  - RNA interference appears as a promising tool for therapeutic gene silencing. A
      key limit is the delivery of the siRNA. A safe approach is to use a physical
      method such as in vivo electropulsation with contact electrodes. Getting a long
      lived silencing can be better approached by using the in situ expression of
      shRNA. This is presently obtained by using co-electrotransfer of specific
      plasmids coding for expression and silencing of a fluorescent protein. Using a
      non invasive fluorescence imaging assay, electrodelivery in mouse muscles is
      observed to induce complete silencing over more than two months in a specific
      way. The proper choices of the plasmids (sequence and relative amounts) and of
      the electric pulsing conditions appear as key parameters in the successful
      silencing.

PMID- 18345700
TI  - High energy shock waves (HESW) increase paclitaxel efficacy in a syngeneic model
      of breast cancer.
AB  - The combined effect of high energy shock waves (HESW), generated by a
      piezoelectric device, and paclitaxel on Mat B-III rat breast cancer cells in
      vitro and in an in vivo animal model is presented. A significant reduction of in
      vitro Mat B-III cell proliferation versus cells treated with paclitaxel alone was
      observed with the combined exposure to paclitaxel (0.1, 1, or 10 nM) and HESW
      (0.22 mJ/mm2, 1000 shots). Moreover earlier induction and enhanced apoptosis
      occurred in cells subjected to the combined treatment with paclitaxel and HESW at
      1 and 10 nM versus paclitaxel alone (p<0.01 and p<0.001, respectively). The
      percentage of apoptotic cells along with BAD mRNA expression, confirm a
      significant enhancement of apoptosis in tumor tissues subjected to the combined
      treatment with paclitaxel (2.5 mg/kg on days 7 and 11) and HESW (0.50 mJ/mm2, 500
      shots on day 11) in comparison with paclitaxel alone. In conclusion, these data
      suggest that HESW enhance paclitaxel cytotoxicity in the Mat B-III syngeneic
      model of breast cancer.

PMID- 18345701
TI  - Development of a novel post-processing treatment planning platform for 4D
      radiotherapy.
AB  - The aim of this study is to develop an Automatic Post-processing Tool for four
      dimensional (4D) treatment planning (APT4D) that enables the user to perform some
      necessary procedures related to 4D treatment planning, such as automated image
      registration, automatic propagation of regions of interest, and dose distribution
      transformation. Demons-based deformable registrations were performed to map the
      moving phase images (such as the end-inhalation phase or 0% phase) to the
      reference phase (typically the end-exhalation fixed phase or 50% phase). Contours
      were automatically propagated into the moving phase using the image registration
      results. The dose distribution of each moving phase was transformed to the fixed
      phase and subsequently was summed as an average with equal weighting factor. To
      validate the application of APT4D utility, the 4D computed tomography (CT) images
      of a lung cancer patient and an abdominal cancer patient were acquired and
      resorted into ten respiratory phases. 4D plans based on the 4D CT images were
      developed. The correlation coefficient ranged from 0.992 to 0.999 for the re
      sampled deformed moving phase image against the fixed phase image for the lung
      patient plan and from 0.977 to 0.999 for the abdominal patient plan. For all the
      organs, the match indices between the manual contours and automatic contour
      propagation results were around 0.92 to 0.95. The 4D composite dose-volume
      histogram showed dosimetric reductions for liver and kidneys in the high dose
      region. The APT4D adds automation, efficiency, and functionality, while
      integrating the whole process of 4D treatment planning.

PMID- 18345702
TI  - Integration of cone-beam CT in stereotactic body radiation therapy.
AB  - This report describes the technique and initial experience using cone beam CT
      (CBCT) for localization of treatment targets in patients undergoing stereotactic
      body radiation therapy (SBRT). Patients selected for SBRT underwent 3-D or 4-D CT
      scans in a customized immobilization cradle. GTV, CTV, ITV, and PTV were defined.
      Intensity-modulated radiation beams, multiple 3-D conformal beams, or dynamic
      conformal arcs were delivered using a Varian 21EX with 120-leaf MLC. CBCT images
      were obtained prior to each fraction, and registered to the planning CT by using
      soft tissue and bony structures to assure accurate isocenter localization.
      Patients were repositioned for treatment based on the CBCT images. Radiographic
      images (kV, MV, or CBCT) were taken before and after beam delivery to further
      assess set-up accuracy. Ten patients with lung, liver, and spine lesions received
      29 fractions of treatment using this technique. The prescription doses ranged
      1250 approximately 6000 cGy in 1 approximately 5 fractions. Compared to
      traditional 2-D matching using bony structures, CBCT corrects target deviation
      from 1 mm to 15 mm, with an average of 5 mm. Comparison of pre-treatment to post
      treatment radiographic images demonstrated an average 2 mm deviation (ranging
      from 0-4 mm). Improved immobilization may enhance positioning accuracy. Typical
      total "in-room" times for the patients are approximately 1 hour. CBCT-guided SBRT
      is feasible and enhances setup accuracy using 3-D anatomical information.

PMID- 18345703
TI  - A Monte-Carlo derived dual-source model for helical tomotherapy treatment
      planning.
AB  - Full Monte Carlo radiation transport simulations of accelerator heads are
      impractical for routine treatment planning because of the excessive computational
      burden and memory requirements. To improve the accuracy and efficiency of
      treatment plans for helical tomotherapy, we have developed a dual-source model to
      characterize the radiation emitted from the head of a commercial helical
      tomotherapy accelerator. Percentage depth dose (PDD) and beam profiles computed
      using the dual-source model with the EGS/BEAMnrc Monte Carlo package agree within
      2% of measurements for a wide range of field sizes, which suggests that the
      proposed dual-source model provides an adequate representation of the tomotherapy
      head for dose calculations in routine treatment planning.

PMID- 18345704
TI  - Application of nanotechnology in cancer.
AB  - Nanotechnology refers broadly to a field of applied science and technology whose
      unifying theme is the control of matter on the molecular level in scales smaller
      than 1 micrometer, normally 1 to 100 nanometers, and the fabrication of devices
      within that size range. In the last five years this technology has been improved
      tremendously in disease diagnosis and prognosis and maximum research and clinical
      work has been completed in cancer. The use of various pharmaceutical nanocarriers
      has become one of the most important areas of nanomedicine. Novel
      nanotechnologies can complement and augment existing genomic and proteomic
      techniques to analyze variations across different tumor types, thus offering the
      potential to distinguish between normal and malignant cells. Sensitive biosensors
      constructed of nanoscale components (e.g., nanocantilevers, nanowires, and
      nanochannels) can recognize genetic and molecular events and have reporting
      capabilities, thereby offering the potential to detect rare molecular signals
      associated with malignancy. Such signals may then be collected for analysis by
      nanoscale harvesters that selectively isolate cancer-related molecules from
      tissues. The implication of nanotechnology in cancer is discussed in this article
      with an emphasis on biomarker detection, imaging studies for diagnosis, and its
      role in therapeutic intervention.

PMID- 18345705
TI  - Prostate cancer vaccines: current status and future potential.
AB  - Standard systemic treatment of prostate cancer today is comprised of antihormonal
      and cytostatic agents. Vaccine therapy of prostate cancer is principally
      attractive because of the presence of tumor-associated antigens such as prostate
      specific antigen (PSA), prostatic acid phosphatase (PAP), prostate-specific
      membrane antigen (PSMA), and others. Most prostate cancer vaccine trials have
      demonstrated some activation of the immune system, limited clinical success, and
      few adverse effects.One strategy to overcome the problem of limited clinical
      success of vaccine therapies in prostate cancer could be strict patient
      selection. The clinical course of patients with prostate cancer (even in those
      with PSA relapse following surgery or radiotherapy with curative intention, or
      those with metastatic disease) can vary significantly. In patients with organ
      confined prostate cancer, the most promising immunotherapeutic approach would be
      an adjuvant therapy following surgery or radiotherapy. Patients with PSA relapse
      following surgery or radiotherapy could also benefit from immunotherapy because
      tumor burden is usually low. However, most patients in prostate cancer vaccine
      trials had metastatic hormone-refractory prostate cancer (HRPC). High tumor
      burden correlates with immune escape phenomena. Nevertheless, 2 years ago, it was
      demonstrated, for the first time, that a tumor vaccine can prolong survival
      compared with placebo in patients with HRPC. This was demonstrated with the
      vaccine sipuleucel-T (APC-8015; Provenge), a mixture of cells obtained from the
      patient's peripheral blood by leukapheresis followed by density centrifugation
      and exposition. The Biologics License Application for this vaccine was denied by
      the US FDA in mid 2007, however, because the trial had failed to reach the
      primary endpoint (prolongation of time to tumor progression). Nevertheless,
      clinical trials with sipuleucel-T are ongoing, and the approach still looks
      promising. Another interesting approach is a vaccine made from whole tumor cells:
      GVAX. This vaccine is presently being studied in phase III trials against, and in
      combination with, docetaxel. The results from these trials will become available
      in the near future. Besides the precise definition of the disease status of
      patients with prostate cancer, combinations of vaccine therapy with radiotherapy,
      chemotherapy, and/or hormonal therapy are approaches that look promising and
      deserve further investigation.

PMID- 18345706
TI  - Cell adhesion antagonists: therapeutic potential in asthma and chronic
      obstructive pulmonary disease.
AB  - Chronic obstructive pulmonary disease (COPD) and asthma are inflammatory diseases
      of the lung where a hallmark feature is excessive leukocyte infiltration that
      leads to tissue injury. Cell adhesion molecules (e.g. selectins and integrins)
      play a key role in cell trafficking, and in the lung they regulate leukocyte
      extravasation, migration within the interstitium, cellular activation, and tissue
      retention. All selectin family members (including L-selectin, P-selectin, and E
      selectin) and many of the beta1 and beta2 integrins appear to be important
      therapeutic targets, as numerous animal studies have demonstrated essential roles
      for these cell adhesion molecules in lung inflammation. Not surprisingly, these
      families of adhesion molecules have been under intense investigation by the
      pharmaceutical industry for the development of novel therapeutics. Integrins are
      validated drug targets, as drugs that antagonize integrin alphaIIbbeta3 (e.g.
      abciximab), integrin alphaLbeta2 (efalizumab), and integrin alpha4beta1
      (natalizumab) are currently US FDA-approved for acute coronary syndromes,
      psoriasis, and multiple sclerosis, respectively. However, none has been approved
      for indications related to asthma or COPD. Here, we provide an overview of roles
      played by selectins and integrins in lung inflammation. We also describe recent
      clinical results (both failures and successes) in developing adhesion molecule
      antagonists, with specific emphasis on those targets that may have potential
      benefit in asthma and COPD. Early clinical trials using selectin and integrin
      antagonists have met with limited success. However, recent positive phase II
      clinical trials with a small-molecule selectin antagonist (bimosiamose) and a
      small-molecule integrin alpha4beta1 antagonist (valategrast [R411]), have
      generated enthusiastic anticipation that novel strategies to treat asthma and
      COPD may be forthcoming.

PMID- 18345707
TI  - Recombinant human growth hormone: rationale for use in the treatment of HIV
      associated lipodystrophy.
AB  - The role of hormonal and metabolic alterations in HIV-associated lipodystrophy
      syndrome is not yet clear. In patients with HIV-1 undergoing antiretroviral
      treatment, lipodystrophy is associated with peripheral fat wasting and central
      adiposity, dyslipidemia, insulin resistance, and increased intramuscular fat
      accumulation. In HIV lipodystrophy, changes in fat distribution are heterogeneous
      and can include reduced subcutaneous fat as well as increased visceral fat. In
      the literature, there is evidence showing that overnight growth hormone (GH)
      secretion and pulse amplitude decrease in patients with HIV lipodystrophy, with
      rates of response to standardized GH stimulation being abnormal in at least 20%
      of these patients. Excess accumulation of visceral fat, central obesity, and
      increased intra-abdominal adiposity are also typical features of patients with GH
      deficiency. Recombinant human GH (rhGH) is a potential treatment to diminish
      excess visceral fat. Our group recently demonstrated that GH therapy in HIV
      infected patients with syndromes of fat accumulation produced a significant
      decrease in body fat and a gain in lean tissue. In this article, we discuss the
      origin of lipodystrophy in HIV patients, and the use of rhGH treatment (benefits
      and adverse effects) in HIV-related lipodystrophy.

PMID- 18345708
TI  - Bevacizumab: in first-line treatment of advanced and/or metastatic renal cell
      carcinoma.
AB  - Bevacizumab, an anti-vascular endothelial growth factor recombinant humanized
      monoclonal antibody, directly inhibits tumor angiogenesis and hence tumor growth.
      First-line therapy with intravenous bevacizumab 10 mg/kg every 2 weeks plus
      subcutaneous interferon-alpha-2a 9 million international units three times weekly
      has been evaluated in two randomized, double-blind or open-label, multicenter
      phase III trials (AVOREN [n = 649] and CALGB 90206 [n = 732]). Bevacizumab
      combination therapy resulted in a median progression-free survival that was
      significantly (p < or = 0.0001) longer than that seen with placebo plus
      interferon-[alpha]-2a in AVOREN (10.2 vs 5.4 months) [hazard ratio (HR) 0.63 (95%
      CI 0.52, 0.75)] and that seen with interferon-alpha-2a alone in CALGB 90206 (8.5
      vs 5.2 months). Overall survival data in AVOREN and CALGB 90206 are not yet
      mature. In the interim overall survival analysis in AVOREN, median overall
      survival was 19.8 months with placebo plus interferon-alpha-2a, but had not yet
      been reached with bevacizumab plus interferon-alpha-2a (HR 0.79 [95% CI 0.62,
      1.02; p = 0.0670]). The overall tumor response rate with bevacizumab plus
      interferon-alpha-2a was significantly (p < or = 0.0001) higher than with placebo
      plus interferon-alpha-2a in AVOREN (31% vs 13%) and that with interferon-alpha-2a
      alone in CALGB 90206 (25.5% vs 13.1%). Subgroup analyses in AVOREN suggested that
      interferon-alpha-2a dose reductions (to manage grade > or =3 adverse events
      attributable to the drug) did not compromise the efficacy of combination
      treatment with bevacizumab plus interferon-alpha-2a. The addition of bevacizumab
      to interferon-alpha-2a in AVOREN was generally well tolerated. No unexpected/new
      adverse events were observed; bevacizumab-associated toxicities were generally of
      mild intensity.

PMID- 18345709
TI  - Recombinant factor VIIa (eptacog alfa): a review of its use in congenital
      hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding
      disorders.
AB  - Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor
      VII or eptacog alfa) is structurally similar to human plasma-derived coagulation
      factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa
      interacts with thrombin-activated platelets to produce a thrombin burst leading
      to accelerated fibrin clot formation localized to the site of vascular injury. It
      is approved in many countries for use as an intravenous hemostatic agent in
      patients with congenital hemophilia with inhibitors, and also for acquired
      hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some
      countries. Studies have shown it to be effective and generally well tolerated
      when used intravenously to treat bleeding episodes or provide hemostatic cover
      during surgery in patients with congenital hemophilia with inhibitors, acquired
      hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available
      data, its efficacy in terms of patient-assessed response may be similar to that
      of activated prothrombin complex concentrate (aPCC), but treatment with a single
      270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue
      therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in
      patients with hemophilia, does not produce an anamnestic response in hemophilia
      patients with inhibitors, and has very low thrombogenicity. It is recommended in
      guidelines as the treatment of choice for bleeds in patients with hemophilia B
      with high-responding inhibitors and for patients with factor VII deficiency, and
      is also a first-line therapeutic option for high-responder hemophilia A patients
      with inhibitors and those with acquired hemophilia. Cost data from
      pharmacoeconomic analyses support its use in hemophilia patients with inhibitors.
      Thus, recombinant factor VIIa is a valuable treatment option for patients with
      these rare, but potentially serious, bleeding disorders.

PMID- 18345710
TI  - Defining the role of insulin lispro in the management of postprandial
      hyperglycaemia in patients with type 2 diabetes mellitus.
AB  - The role of postprandial hyperglycaemia in contributing to the risk of both micro
      and macrovascular complications in patients with diabetes mellitus is being
      increasingly recognized. In type 2 diabetes, there is a progressive shift in the
      relative contributions of postprandial and fasting hyperglycaemia to the overall
      glycaemic control as the disease progresses. For patients with fairly good
      glycaemic control (glycosylated haemoglobin [HbA(1c)] <8.5%), postprandial
      hyperglycaemia makes a relatively greater contribution to the overall glycaemic
      load than fasting hyperglycaemia, but in patients with poorer control, the
      relative contribution of the two states to the overall glycaemic load is
      reversed. This finding, coupled with epidemiological evidence that elevated
      postprandial glucose concentration is an independent risk factor for
      cardiovascular disease (CVD), and is associated with a greater CVD risk than
      elevated fasting glucose, points to the need to monitor and target postprandial
      glucose, as well as fasting glucose and HbA(1c) levels, when optimizing insulin
      therapy for patients with type 2 diabetes. When insulin therapy becomes necessary
      in patients with type 2 diabetes who can no longer be controlled with oral
      antihyperglycaemic therapy, use of short-acting insulin analogues with a rapid
      onset of action and capable of controlling postprandial glycaemic excursions when
      injected immediately before a meal, has advantages over regular human insulin in
      that they provide a more favourable time-action profile that mimics normal
      physiological insulin secretion. Among the available rapid-acting insulin
      analogues, insulin lispro has been shown to reduce postprandial glucose
      concentrations to a significantly greater degree than regular human insulin in
      patients with type 2 diabetes. Moreover, premixed combinations of insulin lispro
      with the longer acting analogue neutral insulin lispro protamine suspension in
      25% : 75% or 50% : 50% combinations are significantly more effective in lowering
      postprandial blood glucose concentrations than premixed regular human insulin
      plus neutral protamine Hagedorn (NPH) 30% : 70%. The premixed insulin lispro
      combinations offer the advantage of fewer daily injections than intensive insulin
      therapy, and the convenience of not having to mix insulin preparations manually.
      Although it has yet to be conclusively established that targeting postprandial
      hyperglycaemia reduces CVD risk, the potential benefits of improved postprandial
      and interprandial hyperglycaemia favour the use of newer insulin analogues, such
      as insulin lispro and insulin lispro mixes, over conventional insulin therapy,
      whenever insulin therapy becomes necessary in patients with type 2 diabetes.

PMID- 18345711
TI  - Economic benefits of treating high-risk hypertension with angiotensin II receptor
      antagonists (blockers).
AB  - Hypertension is one of the leading risk factors for cardiovascular disease and
      represents a major health and economic burden. Most patients with high- or very
      high-risk hypertension have multiple cardiovascular risk factors with or without
      accompanying subclinical organ damage or established cardiovascular or renal
      disease. Patients with severe hypertension or with moderate hypertension and one
      to two additional risk factors have absolute 10-year risks of cardiovascular
      disease of 21-30% and 15-20%, respectively. Current European treatment guidelines
      recommend that antihypertensive therapy be initiated rapidly and aggressively in
      patients with high-risk hypertension. Most patients require two or more
      antihypertensive agents to achieve the strict blood pressure target of <130/80
      mmHg. This article reviews the existing cost-effectiveness data on the use of
      angiotensin II receptor antagonists (blockers) [ARBs] in patients with high-risk
      hypertension. Aggressive ARB treatment of patients in the early
      (microalbuminuric) stages of diabetic nephropathy has a significant
      renoprotective effect, delaying the onset of overt (proteinuric) nephropathy. By
      slowing the progression of these patients to end-stage renal disease, substantial
      cost savings can be made. There is a paucity of cost-effectiveness data regarding
      the use of fixed-dose ARB plus thiazide diuretic combination therapies.
      Longitudinal cost-benefit studies of this attractive and efficacious first-line
      treatment option are needed.

PMID- 18345712
TI  - Non-interventional study comparing treatment satisfaction in patients treated
      with antihistamines.
AB  - BACKGROUND AND OBJECTIVE: Allergic rhinitis and urticaria are common allergic
      disorders that may affect approximately 15% of people at some time in their
      lives. Antihistamines are the most widely used therapeutic interventions for
      these disorders but the newer generation agents have differing pharmacokinetic
      characteristics that may result in different patient satisfaction and
      preferences. The objective of this study was to investigate patients' and
      physicians' satisfaction with their current antihistamine treatment for allergic
      disease. METHODS: In an observational study, physicians in nine European
      countries completed questionnaires evaluating 7,274 patients treated with an oral
      antihistamine. The satisfaction of patients and physicians with the efficacy and
      tolerability of treatment was rated on a visual analogue scale. In addition, the
      proportion of patients satisfied with treatment (overall satisfaction) and
      willing to continue treatment with the same antihistamine were assessed. Safety
      and tolerability data were also gathered. RESULTS: The results of this study
      indicate that modern antihistamines are generally considered effective and well
      tolerated by patients. In general, levocetirizine scored significantly higher in
      terms of perception of efficacy, tolerability and overall satisfaction. In terms
      of tolerability, three-quarters of patients were 'very satisfied' and a further
      fifth were moderately satisfied with levocetirizine and almost all (95%) were
      happy to continue treatment. Overall, the most commonly reported adverse event in
      this study was somnolence, a well known effect of antihistamines. The rate of
      somnolence in the levocetirizine group (3.8%) was similar to that for
      fexofenadine (both doses) and desloratadine, two products which are considered to
      be nonsedating antihistamines, and significantly less than half the rate for
      cetirizine. CONCLUSION: Levocetirizine is considered an effective and well
      tolerated option for treating allergic disease by patients and physicians alike,
      particularly when the best available effectiveness and tolerability are required.

PMID- 18345713
TI  - Bioequivalence of clozapine orally disintegrating 100-mg tablets compared with
      clozapine solid oral 100-mg tablets after multiple doses in patients with
      schizophrenia.
AB  - BACKGROUND: This study compared the bioequivalence of FazaClo (clozapine orally
      disintegrating tablets) 100 mg to Clozaril (clozapine standard oral tablets) 100
      mg after multiple doses in patients with schizophrenia. METHODS: This was a
      randomized, open-label, multiple-dose study in which patients with schizophrenia
      received FazaClo or Clozaril 100 mg twice daily for 5 days before crossing over
      to the alternate therapy. Blood samples were obtained at regular intervals during
      and after the completion of treatment, and standard pharmacokinetic parameters
      were calculated. Safety and patient satisfaction with FazaClo were also assessed.
      RESULTS: Thirty-six patients were enrolled, of whom 33 completed the study and 30
      were included in the steady-state analyses. All pharmacokinetic parameters for
      clozapine and desmethylclozapine (the major metabolite of clozapine) were similar
      between FazaClo and Clozaril in both the completer and steady-state populations.
      Geometric mean values for steady-state maximum and minimum concentrations and
      area under the plasma concentration-time curve for FazaClo were all within 95
      105% of those for Clozarilwell within the range considered by the US FDA as
      acceptable for bioequivalence (80-125%). Patients also expressed a high level of
      satisfaction with the FazaClo orally disintegrating tablet formulation.
      CONCLUSIONS: FazaClo produced pharmacokinetic profiles almost identical to those
      of Clozaril. This should provide clinicians with reassurance that patients who
      receive FazaClo will achieve plasma drug concentrations similar to those produced
      by the same daily dose of Clozaril, and that no cross-titration is necessary when
      switching from one of these clozapine formulations to the other.

PMID- 18345714
TI  - Possible beneficial effect of olmesartan medoxomil on left atrial function in
      patients with hypertension : noninvasive assessment by acoustic quantification.
AB  - BACKGROUND AND OBJECTIVE: Hypertension alters the diastolic properties of the
      left ventricle and results in deterioration in the structure and function of the
      left atrium. We aimed to evaluate whether olmesartan medoxomil has an effect on
      left atrial function in hypertensive patients. METHODS: Fifty hypertensive
      patients and 20 controls were included in the study. Hypertensive patients were
      treated with olmesartan medoxomil for 8 weeks. Before and after treatment, study
      participants were examined by acoustic quantification and tissue Doppler imaging.
      Left atrial reservoir function was assessed by end-diastolic volume (EDV), end
      systolic volume (ESV), reservoir volume (RV) and peak filling rate (PFR). Left
      atrial booster pump function was assessed by atrial emptying volume (AEV), atrial
      emptying fraction (AEF) and peak atrial emptying rate (PAER). Left atrial conduit
      function was assessed by rapid emptying volume (REV), rapid emptying fraction
      (REF), REV/AEV ratio, and the ratio of peak rapid emptying rate and PAER
      (PRER/PAER). RESULTS: Atrial RV and PFR were significantly increased in
      hypertensive subjects (48.30 +/- 19.28 mL vs 34.35 +/- 14.26 mL, p < 0.001;
      267.26 +/- 126.52 mL/s vs 206.81 +/- 107.17 mL/s, p < 0.05) compared with
      controls, while the REV/AEV ratio was decreased in hypertensive patients compared
      with controls (2.86 +/- 0.85 vs 3.69 +/- 2.13, p < 0.001). After therapy with
      olmesartan medoxomil, atrial RV (48.30 +/- 19.28 mL vs 40.50 +/- 17.59 mL) and
      PFR decreased (267.26 +/- 126.52 mL/s vs 220.40 +/- 108.56 mL/s, p < 0.05) and
      the REV/AEV ratio increased (2.86 +/- 0.85 vs 3.14 +/- 0.43, p < 0.05) in
      hypertensive patients. CONCLUSION: Our novel findings indicate that left atrial
      function is impaired in hypertensive patients, and that olmesartan medoxomil can
      improve left atrial function in this context. Our study also showed that acoustic
      quantification is useful for non-invasive evaluation of the benefits of treatment
      on left atrial function.

PMID- 18345715
TI  - Venlafaxine versus mirtazapine in the treatment of undifferentiated somatoform
      disorder: a 12-week prospective, open-label, randomized, parallel-group trial.
AB  - OBJECTIVE: We set out to compare the efficacy and tolerability of mirtazapine
      versus venlafaxine in patients with undifferentiated somatoform disorder (USD)
      using the Patient Health Questionnaire-15 (PHQ-15). METHODS: This was a 12-week
      prospective, open-label, randomized, parallel-group trial. The trial consisted of
      six visits that included baseline and weeks 1, 2, 4, 8 and 12. The primary
      effectiveness measure was the mean change in PHQ-15 total score from baseline to
      the end of treatment. Secondary effectiveness measures included the mean changes
      in total scores on the Beck Depression Inventory (BDI) and the 12-item General
      Health Questionnaire (GHQ) from baseline to the end of treatment. Ninety-five
      subjects were randomized to either mirtazapine (n = 50) or venlafaxine (n = 45);
      71 subjects completed the study (mirtazapine: n = 39/50 [78%]; venlafaxine: n =
      32/45 [71%]). RESULTS: The mean total score on the PHQ-15 decreased by 34.7% (
      8.4, p < 0.0001) from baseline to endpoint in the mirtazapine group and by 26.6%
      (-6.1, p < 0.0001) in the venlafaxine group. A marginally significant between
      group difference was observed for the mean change in total score on the PHQ-15
      from baseline to endpoint (F = 4.126, p = 0.046). The mean total scores on the
      GHQ-12 and BDI from baseline to endpoint decreased by -4.9 (29.4%, p < 0.0001)
      and -13.5 (55.9%, p < 0.0001), respectively, in the mirtazapine group, and by 
      4.3 (26.2%, p = 0.001) and -9.02 (46.0%, p < 0.0001), respectively, in the
      venlafaxine group. No between-group difference was observed for the mean changes
      in total scores on the secondary effectiveness measures from baseline to
      endpoint. Both treatments were well tolerated. CONCLUSION: Our findings suggest
      that both mirtazapine and venlafaxine may be effective and well tolerated in the
      treatment of patients with USD. Double-blind, placebo-controlled and/or head-to
      head comparison studies are required to allow definite conclusions to be drawn.

PMID- 18345716
TI  - The infancy of an international pediatric pharmacy network.

PMID- 18345717
TI  - Acute otitis media in children: association with day care centers--antibacterial
      resistance, treatment, and prevention.
AB  - Children attending day care centers (DCCs) frequently carry antibacterial
      resistant organisms in their nasopharynx, leading to acute otitis media (AOM)
      that may be refractory to antibacterial treatment. The development and spread of
      resistant organisms are facilitated in DCCs as a result of the following: (i)
      large numbers of children; (ii) frequent close person-to-person contact; and
      (iii) a wide use of antimicrobial medications. Intensive antimicrobial usage
      provides the selection pressure that favors the emergence of resistant organisms,
      while DCCs provide an ideal environment for transmission of these organisms. The
      American Academy of Pediatrics and American Academy of Family Physicians'
      guidelines recommend high-dose amoxicillin/clavulanic acid (rather than
      amoxicillin alone) as the first therapeutic choice in the treatment of AOM in
      children attending DCCs. The introduction of the 7-valent pneumococcal conjugated
      vaccine (PCV7) had a major role in decreasing the number of episodes of
      Streptococccus pneumoniae AOM secondary to the serotypes included in the vaccine.
      It also had a major role in reducing the nasopharyngeal carriage of vaccine-type
      S. pneumoniae (and in particular of antibacterial-resistant organisms),
      preventing, in this way, its spread to contacts in the community. However, the
      recent observation of increased rates of antibacterial-resistant non-vaccine
      serotype S. pneumoniae may erode the success of PCV7.

PMID- 18345718
TI  - Molecularly targeted therapies for pediatric acute myeloid leukemia: progress to
      date.
AB  - While acute myeloid leukemia (AML) is significantly less common than acute
      lymphoblastic leukemia (ALL) in childhood, it is significantly more deadly with
      only half as many children likely to be cured with standard therapy. In addition,
      the typical treatment for AML is among the most toxic of treatments for pediatric
      cancer; it includes intensive multiagent chemotherapy and, often, hematopoietic
      stem cell transplantation. Given the poor prognosis of pediatric AML and the
      significant toxicity of standard AML therapy, novel therapies are needed.
      Improved understanding of the molecular and cellular biology of leukemia has
      facilitated the development of molecularly targeted therapies. In this article,
      we review progress to date with agents that are showing promise in the treatment
      of pediatric AML including targeted immunoconjugates, inhibitors of signaling
      molecules (e.g. FMS-like tyrosine kinase 3 [FLT3], farnesyltransferase, and
      mammalian target of rapamycin [mTOR]), agents that target epigenetic regulation
      of gene expression (DNA methyltransferase inhibitors and histone deacetylase
      inhibitors), and proteasome inhibitors. For the specific agents in each of these
      classes, we summarize the published preclinical data and the clinical trials that
      have been completed, are in progress, or are being planned for children with AML.
      Finally, we discuss potential challenges to the success of molecularly targeted
      therapy including demonstrating adequate targeting of leukemia stem cells,
      developing synergistic and tolerable combinations of agents, and designing
      adequately powered clinical trials to test efficacy in molecularly defined
      subsets of patients.

PMID- 18345720
TI  - Regional anesthesia for postoperative pain control in children: focus on
      continuous central and perineural infusions.
AB  - Regional anesthesia is widely employed for postoperative pain control in both
      adults and children. Central or perineural approaches can be performed as a bolus
      injection or as a continuous infusion of local anesthetics. However, bolus
      injections, even with the addition of adjuvants, are inadequate for prolonged
      surgery and long-term pain control. Continuous infusion remains the technique of
      choice when there is a prolonged operation or intense postoperative pain. This
      article reviews the safety and efficacy of central and perineural continuous
      infusions for postoperative pain control in children. The literature confirms the
      very low rate of complications and adverse effects of regional anesthesia in
      children. However, clinicians need to be aware of the key points for performing a
      block and placing a catheter in children: good knowledge of anatomic and
      physiologic differences between adults and children is necessary; the use of
      newer local anesthetics, such as ropivacaine and levobupivacaine, increases the
      therapeutic window; and that it is mandatory to work with dedicated pediatric
      equipment. Through the use of new techniques such as nerve mapping and/or
      ultrasound the success of blocks can be improved and the risks reduced.

PMID- 18345719
TI  - Emerging chemotherapeutic strategies and the role of treatment stratification in
      Ewing sarcoma.
AB  - The Ewing sarcoma family of tumors (ESFT) is one of the most common groups of
      malignancies arising in children, adolescents, and young adults up to
      approximately 25 years of age. It comprises Ewing sarcoma arising from bone and
      extraosseous Ewing sarcoma arising from soft tissues (which includes peripheral
      neuroectodermal tumors and Askin tumor arising from the chest wall). Ewing
      sarcoma is treated successfully in many cases by a combination of chemotherapy,
      surgery, and radiotherapy. A number of prognostic factors have been identified
      that can be used to stratify patients according to the risk of relapse, allowing
      optimization of treatment. These can be categorized as tumor-related factors
      (presence of metastases, tumor site, volume, lactic dehydrogenase level,
      chromosomal translocation type, presence of fusion transcripts in blood and bone
      marrow), treatment-related factors (local therapy, histologic response to
      chemotherapy, radiologic response to chemotherapy, chemotherapy regimen), and
      patient-related factors (gender, age). Newer chemotherapeutic agents are
      currently being investigated, and there is now increasing interest in the
      identification of molecular targets in ESFT that could be exploited
      therapeutically, which include the mammalian target of rapamycin (mTOR) and
      insulin growth factor-1 (IGF-1) receptor pathways.

PMID- 18345721
TI  - Current and emerging chemotherapy treatment strategies for Wilms tumor in North
      America.
AB  - Wilms tumor is the most common primary renal malignancy occurring in childhood.
      Approximately 500 children are diagnosed with Wilms tumor annually in the US
      alone, most of whom are aged <5 years. Several prognostic factors have been
      identified, including stage of disease, tumor histology, patient age, tumor
      weight, and tumor-specific loss of heterozygosity for chromosomes 1p and 16q.
      During the period from 1969 to 2002, the National Wilms Tumor Study Group
      coordinated five multicenter Wilms tumor studies. The overall survival rate for
      Wilms tumor has risen to >90% for patients with tumors of favorable histology.
      However, the treatment of patients with Wilms tumor with anaplastic histology
      remains challenging. The optimal treatment strategies for Wilms tumor in relapse
      will be studied via international collaboration in the near future. Goals of
      emerging studies include minimizing toxicity while maintaining the outstanding
      cure rates for patients with a good prognosis and, through advancing biologic
      understanding and developing novel therapeutic approaches, improving the
      prognosis for those patients in whom effective cure of their disease continues to
      elude physicians.

PMID- 18345722
TI  - Pediatric heart failure therapy with beta-adrenoceptor antagonists.
AB  - Management of chronic heart failure in pediatrics has been altered by the adult
      literature showing improvements in mortality and hospitalization rates with the
      use of beta-adrenoceptor antagonists (beta-blockers) for routine therapy of all
      classes of ischemic and non-ischemic heart failure. Many pediatric heart failure
      specialists have incorporated these agents into their routine management of
      pediatric heart failure related to dilated cardiomyopathy or ventricular
      dysfunction in association with congenital heart disease. Retrospective and small
      prospective case series have shown encouraging improvements in cardiac function
      and symptoms, but interpretation has been complicated by the high rate of
      spontaneous recovery in pediatric patients. A recently completed pediatric double
      blind, randomized, placebo-controlled clinical trial showed no difference between
      placebo and two doses of carvedilol over a 6-month period of follow-up, with
      significant improvement of all three groups over the course of evaluation.
      Experience with adults has suggested that only certain beta-blockers, including
      carvedilol, bisoprolol, nebivolol, and metoprolol succinate, should be used in
      the treatment of heart failure and that patients with high-grade heart failure
      may derive the most benefit. Other studies surmise that early or prophylactic use
      of these medications may alter the risk of disease progression in some high-risk
      subsets, such as patients receiving anthracyclines or those with muscular
      dystrophy. This article reviews these topics using experience as well as data
      from all the recent pediatric studies on the use of beta-blockers to treat
      congestive heart failure, especially when related to systolic ventricular
      dysfunction.

PMID- 18345723
TI  - Determinants of aciclovir-induced nephrotoxicity in children.
AB  - BACKGROUND: Aciclovir is the drug of choice for severe systemic herpes virus
      infections. Nephrotoxicity is one of the clinically significant adverse effects
      of this drug, but studies examining nephrotoxicity in children are scarce.
      OBJECTIVE: To identify risk factors for aciclovir-associated nephrotoxicity in
      the pediatric population. PATIENTS AND METHODS: A retrospective review was
      conducted on all children (mean age 81 months; n = 126 [74 boys]) who were
      treated with aciclovir in a tertiary center between July 2005 and January 2006
      and who met our inclusion criteria. Glomerular filtration rate (GFR) was
      calculated on the first day of treatment and at the peak measured creatinine
      level while on therapy, using Schwartz's method. RESULTS: Aciclovir therapy was
      associated with a significant increase in serum creatinine levels and a parallel
      decrease in GFR (n = 93; both p <or= 0.0001). Children with immunosuppression who
      received a variety of other nephrotoxic drugs exhibited more severe
      nephrotoxicity than those not receiving nephrotoxic drugs. In multiple regression
      analysis, the use of nephrotoxic drugs (p = 0.02) and impaired GFR at baseline (p
      = 0.04) were predictive for nephrotoxicity. CONCLUSIONS: Within the recommended
      age-dependent dosage schedule of aciclovir there was no effect of dose per kg,
      age, or sex on nephrotoxicity. The predictors of aciclovir nephrotoxicity were
      the concomitant use of nephrotoxic drugs and impaired GFR at baseline.

PMID- 18345724
TI  - Improved prewhitening method for linear frequency modulation reverberation using
      dechirping transformation.
AB  - This letter presents an autoregressive (AR) prewhitener for linear frequency
      modulation (LFM) reverberation to enhance the target signal. The proposed method
      uses a dechirping transformation to inversely compensate the frequency chirp rate
      of the LFM and give the LFM reverberation a stationary frequency property in each
      data block. The left or right beam signal adjacent to the current beam is then
      used as the reference signal, and the frequency response of each data block
      modeled using the AR coefficients. Finally, these coefficients are used to
      implement the inverse filter and efficiently prewhiten the LFM reverberation of
      the current beam.

PMID- 18345725
TI  - Small-scale seismic inversion using surface waves extracted from noise cross
      correlation.
AB  - Green's functions can be retrieved between receivers from the correlation of
      ambient seismic noise or with an appropriate set of randomly distributed sources.
      This principle is demonstrated in small-scale geophysics using noise sources
      generated by human steps during a 10-min walk in the alignment of a 14-m-long
      accelerometer line array. The time-domain correlation of the records yields two
      surface wave modes extracted from the Green's function between each pair of
      accelerometers. A frequency-wave-number Fourier analysis yields each mode
      contribution and their dispersion curve. These dispersion curves are then
      inverted to provide the one-dimensional shear velocity of the near surface.

PMID- 18345726
TI  - Evoking biphone neighborhoods with verbal transformations: illusory changes
      demonstrate both lexical competition and inhibition.
AB  - When a recorded verbal stimulus repeats over and over, perceptual changes occur
      and listeners hear competing forms. These verbal transformations (VTs) were
      obtained for a phonemically related set of 24 consonant-vowel syllables that
      varied widely in frequency-weighted neighborhood density (FWND). Listener's
      initial transformations involving substitution of consonants versus vowels were
      strongly correlated with the lexical substitution neighborhood [r=+0.82,
      p<0.0001]. Interestingly, as stimulus FWND increased, average time spent hearing
      illusory forms substantially decreased [r=-0.75, p<0.0001]. These results suggest
      that VTs not only reveal underlying competitors, but also provide a highly
      sensitive measure of lexical inhibition.

PMID- 18345812
TI  - Comparing turbulence models for flow through a rigid glottal model.
AB  - Flow through a rigid model of the human vocal tract featuring a divergent glottis
      was numerically modeled using the Reynolds-averaged Navier-Stokes approach. A
      number of different turbulence models, available in a widely used commercial
      computational fluid dynamics code, were tested to determine their ability to
      capture various flow features recently observed in laboratory experiments and
      large eddy simulation studies. The study reveals that results from unsteady
      simulations employing the k-omega shear stress transport model were in much
      better agreement with previous measurements and predictions with regard to the
      ability to predict glottal jet skewing due to the Coanda effect and the
      intraglottal pressure distribution or related skin friction coefficient, than
      either steady or unsteady simulations using the Spalart-Allmaras model or any
      other two-equation turbulence model investigated in this study.

PMID- 18345813
TI  - Near field Rayleigh wave on soft porous layers.
AB  - Simulations performed for a typical semi-infinite reticulated plastic foam
      saturated by air show that, at distances less than three Rayleigh wavelengths
      from the area of mechanical excitation by a circular source, the normal frame
      velocity is close to the Rayleigh pole contribution. Simulated measurements show
      that a good order of magnitude estimate of the phase speed and damping can be
      obtained at small distances from the source. Simulations are also performed for
      layers of finite thickness, where the phase velocity and damping depend on
      frequency. They indicate that the normal frame velocity at small distances from
      the source is always close to the Rayleigh pole contribution and that a good
      order of magnitude estimate of the phase speed of the Rayleigh wave can be
      obtained at small distances from the source. Furthermore, simulations show that
      precise measurements of the damping of the Rayleigh wave need larger distances.
      Measurements performed on a layer of finite thickness confirm these trends.

PMID- 18345814
TI  - Attenuation and scattering of axisymmetrical modes in a fluid-filled round pipe
      with internally rough walls.
AB  - The attenuation of axisymmetric eigenmodes in a cylindrical, elastic, fluid
      filled waveguide with a statistically rough elastic wall is studied. It is shown
      that small perturbation theory can be used to relate explicitly the statistical
      characteristics of the internal wall surface roughness of an elastic pipe to the
      attenuation and scattering coefficients of the acoustic modes in the filling
      fluid. Analytical expressions for modal attenuation coefficients are obtained.
      The analysis of the frequency dependent attenuation coefficients and the ratio
      between the roughness correlation length and the inner radius of the pipe is made
      for different correlation functions of the roughness. It is shown that two scale
      parameters control the overall behavior of the modal attenuation coefficients.
      These are the ratios of the roughness correlation length and the inner pipe
      radius to the acoustic wavelength. The numerical results for sound propagation in
      a pipe and in a borehole with statistically rough, elastic walls are obtained and
      discussed.

PMID- 18345815
TI  - Low frequency wind noise contributions in measurement microphones.
AB  - In a previous paper [R. Raspet, et al., J. Acoust. Soc. Am. 119, 834-843 (2006)],
      a method was introduced to predict upper and lower bounds for wind noise measured
      in spherical wind-screens from the measured incident velocity spectra. That paper
      was restricted in that the predictions were only valid within the inertial range
      of the incident turbulence, and the data were from a measurement not specifically
      designed to test the predictions. This paper extends the previous predictions
      into the source region of the atmospheric wind turbulence, and compares the
      predictions to measurements made with a large range of wind-screen sizes.
      Predictions for the turbulence-turbulence interaction pressure spectrum as well
      as the stagnation pressure fluctuation spectrum are calculated from a form fit to
      the velocity fluctuation spectrum. While the predictions for turbulence
      turbulence interaction agree well with measurements made within large (1.0 m)
      wind-screens, and the stagnation pressure predictions agree well with unscreened
      gridded microphone measurements, the mean shear-turbulence interaction spectra do
      not consistently appear in measurements.

PMID- 18345816
TI  - Range-dependent waveguide scattering model calibrated for bottom reverberation in
      a continental shelf environment.
AB  - An analytic model is developed for scattering from random inhomogeneities in
      range-dependent ocean waveguides using the Rayleigh-Born approximation to Green's
      theorem. The expected scattered intensity depends on statistical moments of
      fractional changes in compressibility and density, which scatter as monopoles and
      dipoles, respectively, and the coherence volume of the inhomogeneities. The model
      is calibrated for ocean bottom scattering using data acquired by instantaneous
      wide-area ocean acoustic waveguide remote sensing (OAWRS) and geophysical surveys
      of the ONR Geoclutter Program. The scattering strength of the seafloor on the New
      Jersey shelf, a typical continental shelf environment, is found to depend on wave
      number k, medium coherence volume V(c), and seabed depth penetration factor F(p)
      following a 10 log(10)(F(p)V(c)k(4)) dependence. A computationally efficient
      numerical approach is developed to rapidly compute bottom reverberation over wide
      areas using the parabolic equation by exploiting correlation between monopole and
      dipole scattering terms and introducing seafloor depth penetration factors. An
      approach is also developed for distinguishing moving clutter from statistically
      stationary background reverberation by tracking temporal and spatial fluctuations
      in OAWRS intensity images.

PMID- 18345817
TI  - Bottom profiling by correlating beam-steered noise sequences.
AB  - It has already been established that by cross-correlating ambient noise time
      series received on the upward and downward steered beams of a drifting vertical
      array one can obtain a subbottom layer profile. Strictly, the time differential
      of the cross correlation is the impulse response of the seabed. Here it is shown
      theoretically and by simulation that completely uncorrelated surface noise
      results in a layer profile with predictable amplitudes proportional to those of
      an equivalent echo sounder at the same depth as the array. The phenomenon is
      simulated by representing the sound sources as multiple random time sequences
      emitted from random locations in a horizontal plane above a vertical array and
      then accounting for the travel times of the direct and bottom reflected paths. A
      well-defined correlation spike is seen at the depth corresponding to the bottom
      reflection despite the fact that the sound sources contain no structure
      whatsoever. The effects of using simultaneously steered upward and downward
      conical beams with a tilted or faceted seabed and multiple layers are also
      investigated by simulation. Experimental profiles are obtained using two
      different vertical arrays in smooth and rough bottom sites in the Mediterranean.
      Correlation peak amplitudes follow the theory and simulations closely.

PMID- 18345818
TI  - Passive fathometer processing.
AB  - Ocean acoustic noise can be processed efficiently to extract Green's function
      information between two receivers. By using noise array-processing techniques, it
      has been demonstrated that a passive array can be used as a fathometer [Siderius,
      et al., J. Acoust. Soc. Am. 120, 1315-1323 (2006)]. Here, this approach is
      derived in both frequency and time domains and the output corresponds to the
      reflection sequence. From this reflection sequence, it is possible to extract
      seabed layering. In the ocean waveguide, most of the energy is horizontally
      propagating, whereas the bottom information is contained in the vertically
      propagating noise. Extracting the seabed information requires a dense array,
      since the resolution of the bottom layer is about half the array spacing. If
      velocity sensors are used instead of pressure sensors, the array spacing
      requirement can be relaxed and simulations show that just one vertical velocity
      sensor is sufficient.

PMID- 18345819
TI  - Joint time/frequency-domain inversion of reflection data for seabed geoacoustic
      profiles and uncertainties.
AB  - This paper develops a joint time/frequency-domain inversion for high-resolution
      single-bounce reflection data, with the potential to resolve fine-scale profiles
      of sediment velocity, density, and attenuation over small seafloor footprints
      (approximately 100 m). The approach utilizes sequential Bayesian inversion of
      time- and frequency-domain reflection data, employing ray-tracing inversion for
      reflection travel times and a layer-packet stripping method for spherical-wave
      reflection-coefficient inversion. Posterior credibility intervals from the travel
      time inversion are passed on as prior information to the reflection-coefficient
      inversion. Within the reflection-coefficient inversion, parameter information is
      passed from one layer packet inversion to the next in terms of marginal
      probability distributions rotated into principal components, providing an
      efficient approach to (partially) account for multi-dimensional parameter
      correlations with one-dimensional, numerical distributions. Quantitative
      geoacoustic parameter uncertainties are provided by a nonlinear Gibbs sampling
      approach employing full data error covariance estimation (including nonstationary
      effects) and accounting for possible biases in travel-time picks. Posterior
      examination of data residuals shows the importance of including data covariance
      estimates in the inversion. The joint inversion is applied to data collected on
      the Malta Plateau during the SCARAB98 experiment.

PMID- 18345820
TI  - Controlled and in situ target strengths of the jumbo squid Dosidicus gigas and
      identification of potential acoustic scattering sources.
AB  - This study presents the first target strength measurements of Dosidicus gigas, a
      large squid that is a key predator, a significant prey, and the target of an
      important fishery. Target strength of live, tethered squid was related to mantle
      length with values standardized to the length squared of -62.0, -67.4, -67.9, and
      -67.6 dB at 38, 70, 120, and 200 kHz, respectively. There were relatively small
      differences in target strength between dorsal and anterior aspects and none
      between live and freshly dead squid. Potential scattering mechanisms in squid
      have been long debated. Here, the reproductive organs had little effect on squid
      target strength. These data support the hypothesis that the pen may be an
      important source of squid acoustic scattering. The beak, eyes, and arms, probably
      via the sucker rings, also play a role in acoustic scattering though their
      effects were small and frequency specific. An unexpected source of scattering was
      the cranium of the squid which provided a target strength nearly as high as that
      of the entire squid though the mechanism remains unclear. Our in situ
      measurements of the target strength of free-swimming squid support the use of the
      values presented here in D. gigas assessment studies.

PMID- 18345821
TI  - Demonstration of the invariance principle for active sonar.
AB  - Active sonar systems can provide good target detection potential but are limited
      in shallow water environments by the high level of reverberation produced by the
      interaction between the acoustic signal and the ocean bottom. The nature of the
      reverberation is highly variable and depends critically on the ocean and seabed
      properties, which are typically poorly known. This has motivated interest in
      techniques that are invariant to the environment. In passive sonar, a scalar
      parameter termed the waveguide invariant, has been introduced to describe the
      slope of striations observed in lofargrams. In this work, an invariant for active
      sonar is introduced. This active invariant is shown to be present in the time
      frequency structure observed in sonar data from the Malta Plateau, and the
      structure agrees with results produced from normal mode simulations. The
      application of this feature in active tracking algorithms is discussed.

PMID- 18345822
TI  - Waveguide invariant focusing for broadband beamforming in an oceanic waveguide.
AB  - The performance of broadband sonar array processing can degrade significantly in
      shallow-water environments when interference becomes angularly spread due to
      multipath propagation. Particularly for towed line arrays near endfire, elevation
      angle spreading of multipath interference often results in masking of weaker
      sources of interest. While adaptive beamforming in a series of narrow frequency
      bands can suppress coherent multipath interference, this approach requires long
      observation times to estimate the required narrowband covariance matrices. To
      form wideband covariance matrices which can be estimated with less observation
      time, plane-wave focusing methods have been used to avoid interference covariance
      matrix rank inflation. This paper extends wideband focusing to the case of
      coherent multipath interference. The approach presented here, called waveguide
      invariant focusing (WIF), exploits a robust relationship for the frequency
      dependence of horizontal wave number differences. Unlike matched-field methods,
      WIF does not model multipath wave fronts but rather makes the interference appear
      to occupy the same rank-one subspace across frequency. This permits formation of
      wideband covariance matrices without interference rank inflation. Simulation
      experiments in a realistic ocean environment indicate that adaptive beamforming
      using WIF covariance matrices can provide a significant array gain improvement
      over conventional adaptive methods with limited observation time.

PMID- 18345823
TI  - Efficient absorbing boundary conditions for Biot's equations in time-harmonic
      finite element applications.
AB  - Absorbing boundary conditions for two phase media previously presented by Zerfa
      and Loret [Earthquake Eng. Struct. Dyn. 33, 89-110 (2004)] have been improved by
      considering additionally absorbing waves with auxiliary angles of incidence.
      These angles are defined at each point on the boundaries, so one can easily
      implement tensor impedances as analogous to those defined by Krenk and Kirkegaard
      for isotropic, nonporous media [J. Sound Vib. 247, 875-896 (2001)]. The boundary
      conditions have been tested and validated in two-dimensional frequency domain
      simulations.

PMID- 18345824
TI  - Predicted attenuation of sound in a rigid-porous ground from an airborne source.
AB  - An approximate analytical formula has been derived for the prediction of sound
      fields in a semi-infinite rigid-porous ground due to an airborne source. The
      method starts by expressing the sound fields in an integral form, which can
      subsequently be evaluated by the method of steepest descents. The concept of
      effective impedance has been introduced by using a physically plausible
      assumption. The integral can then be simplified and evaluated analytically. The
      analytical solution can be expressed in a closed form analogous to the classical
      Weyl-Van der Pol formula that has been used for predicting sound fields above a
      rigid-porous ground. Extensive comparisons with the wave-based numerical
      solutions according to the fast field formulation and the direct evaluation of
      the integral have been conducted. It has been demonstrated that the analytical
      formula is sufficiently accurate to predict the penetration of sound into a wide
      range of outdoor ground surfaces.

PMID- 18345825
TI  - Thermal boundary layer effects on the acoustical impedance of enclosures and
      consequences for acoustical sensing devices.
AB  - Expressions are derived for the acoustical impedance of a rectangular enclosure
      and of a finite annular cylindrical enclosure. The derivation is valid throughout
      the frequency range in which all dimensions of the enclosure are much less than
      the wavelength. The results are valid throughout the range from adiabatic to
      isothermal conditions in the enclosure. The effect is equivalent to placing an
      additional, frequency-dependent complex impedance in parallel with the adiabatic
      compliance. As the thermal boundary layer grows to fill the cavity, the reactive
      part of the impedance varies smoothly from the adiabatic value to the isothermal
      value. In some microphones, this change in cavity stiffness is sufficient to
      modify the sensitivity. The resistive part of the additional cavity impedance
      varies as the inverse square root of frequency at high frequencies where the
      boundary layer has not grown to fill the enclosure. The thermal modification
      gives rise to a thermal noise whose spectral density varies asymptotically as
      l/f(3/2) above the isothermal transition frequency.

PMID- 18345826
TI  - Elastic wave field computation in multilayered nonplanar solid structures: a mesh
      free semianalytical approach.
AB  - Multilayered solid structures made of isotropic, transversely isotropic, or
      general anisotropic materials are frequently used in aerospace, mechanical, and
      civil structures. Ultrasonic fields developed in such structures by finite size
      transducers simulating actual experiments in laboratories or in the field have
      not been rigorously studied. Several attempts to compute the ultrasonic field
      inside solid media have been made based on approximate paraxial methods like the
      classical ray tracing and multi-Gaussian beam models. These approximate methods
      have several limitations. A new semianalytical method is adopted in this article
      to model elastic wave field in multilayered solid structures with planar or
      nonplanar interfaces generated by finite size transducers. A general formulation
      good for both isotropic and anisotropic solids is presented in this article. A
      variety of conditions have been incorporated in the formulation including
      irregularities at the interfaces. The method presented here requires frequency
      domain displacement and stress Green's functions. Due to the presence of
      different materials in the problem geometry various elastodynamic Green's
      functions for different materials are used in the formulation. Expressions of
      displacement and stress Green's functions for isotropic and anisotropic solids as
      well as for the fluid media are presented. Computed results are verified by
      checking the stress and displacement continuity conditions across the interface
      of two different solids of a bimetal plate and investigating if the results for a
      corrugated plate with very small corrugation match with the flat plate results.

PMID- 18345827
TI  - Dual mode tuning strategy of a slightly asymmetric ring.
AB  - Clear beats with proper periods in the first and the second vibration modes are
      very important factors for the sound of the Korean bell. In this study, the
      Korean bell is expressed as a circular ring with multiple point masses and a dual
      mode tuning strategy for clear beat with proper period. For the dual mode tuning,
      a dual mode equivalent ring model is composed with two point masses, which
      satisfies the mode pair conditions of the first mode and second mode
      simultaneously. By adding a suitable amount of additional masses to the dual mode
      equivalent ring model at appropriate positions, a clear beat with proper period
      in both of the two important modes is generated. The position and amount of the
      additional masses are determined analytically. Analytical tuning results are
      compared and verified with those of the finite element analysis.

PMID- 18345828
TI  - Inclusion of localized forces due to turbulent boundary layer convected pressure
      at junctions of coplanar structural sections.
AB  - Previous researchers showed that the concept of turbulent boundary layer (TBL)
      "edge forces," which are related to the convection peak of the TBL pressure wave
      number spectral density, is useful and important when using a finite element
      model to compute the bending response to TBL excitation of a plate that has a
      free edge. This paper examines the applicability of more general localized forces
      to the junction of two distinct coplanar sections that are joined along a line
      transverse to the flow. A formalism is developed for introducing these forces and
      applying them to a structure. The approach is made plausible by using two string
      sections as a simple structural model and showing that the sum of the localized
      force response and that due to the low wave number excitation matches the
      separately computed response corresponding to the full wave number spectral
      density. These localized forces can have a noticeable effect when the connection
      between sections is resilient.

PMID- 18345829
TI  - Diffuse wave density and directionality in anisotropic solids.
AB  - Several general results are derived for diffuse waves in anisotropic solids,
      including concise expressions for the modal density per unit volume d(omega), and
      for the participation factor matrix G. The latter is a second-order tensor which
      describes the orientational distribution of diffuse wave or reverberant energy,
      and reduces to the identity I under isotropy. Calculations of G for a variety of
      example materials show significant deviation from I even under moderate levels of
      anisotropy.

PMID- 18345830
TI  - Perturbations of the seismic reflectivity of a fluid-saturated depth-dependent
      poroelastic medium.
AB  - Analytical formulas are derived to compute the first-order effects produced by
      plane inhomogeneities on the point source seismic response of a fluid-filled
      stratified porous medium. The derivation is achieved by a perturbation analysis
      of the poroelastic wave equations in the plane-wave domain using the Born
      approximation. This approach yields the Frechet derivatives of the P-SV- and SH
      wave responses in terms of the Green's functions of the unperturbed medium. The
      accuracy and stability of the derived operators are checked by comparing, in the
      time-distance domain, differential seismograms computed from these analytical
      expressions with complete solutions obtained by introducing discrete
      perturbations into the model properties. For vertical and horizontal point
      forces, it is found that the Frechet derivative approach is remarkably accurate
      for small and localized perturbations of the medium properties which are
      consistent with the Born approximation requirements. Furthermore, the first-order
      formulation appears to be stable at all source-receiver offsets. The porosity,
      consolidation parameter, solid density, and mineral shear modulus emerge as the
      most sensitive parameters in forward and inverse modeling problems. Finally, the
      amplitude-versus-angle response of a thin layer shows strong coupling effects
      between several model parameters.

PMID- 18345831
TI  - Rectangular plate with velocity feedback loops using triangularly shaped
      piezoceramic actuators: experimental control performance.
AB  - This paper presents experimental results on the implementation of decentralized
      velocity feedback control on a new smart panel in order to produce active
      damping. The panel is equipped with 16 triangularly shaped piezoceramic patch
      actuators along its border and accelerometer sensors located at the top vertex of
      the triangular actuators. The primary objective of this paper is to demonstrate
      the vibration and sound radiation control using the new smart panel. Narrow
      frequency band experimental results highlight that the 16 control units can
      produce reductions up to 15 dB at resonance frequencies between 100 and 700 Hz in
      terms of both structural vibration and sound power radiation.

PMID- 18345832
TI  - Reduction of turbulent boundary layer induced interior noise through active
      impedance control.
AB  - The use of a single actuator tuned to an optimum impedance to control the sound
      power radiated from a turbulent boundary layer (TBL) excited aircraft panel into
      the aircraft interior is examined. An approach to calculating the optimum
      impedance is defined and the limitations on the reduction in radiated power by a
      single actuator tuned to that impedance are examined. It is shown that there are
      too many degrees of freedom in the TBL and in the radiation modes of the panel to
      allow a single actuator to control the radiated power. However, if the panel
      modes are lightly damped and well separated in frequency, significant reductions
      are possible. The implementation of a controller that presents a desired
      impedance to a structure is demonstrated in a laboratory experiment, in which the
      structure is a mass. The performance of such a controller on an aircraft panel is
      shown to be effective, if the actuator impedance is similar to but not the same
      as the desired impedance, provided the panel resonances are well separated in
      frequency and lightly damped.

PMID- 18345833
TI  - Assessment of asphalt concrete acoustic performance in urban streets.
AB  - Geo-referenced close proximity rolling noise and sound absorption measurements
      are used for acoustical characterization of asphalt concrete surfaces in an urban
      environment. A close proximity noise map of streets with low speed limits is
      presented for a reference speed of 50 km/h. Different pavements and pavement
      conditions, common in urban streets, are analyzed: dense and semidense asphalt
      concrete, with Spanish denomination D-8 and S-12, respectively, and on the other
      hand, dense pavement at the end of its service life (D-8(*)). From the acoustics
      point of view, the most favorable surface, by more than 4 dB(A) compared with the
      S-12 mix, is the smoothest surface, i.e., the D-8 mix, even though it presents a
      minor absorption coefficient in normal incidence. Noise levels from dense
      surfaces (D-8) increase significantly over time, principally due to the
      appearance of surface defects such as cracks and ruts. Longitudinal variability
      of the close proximity tire/pavement noise emission and surface homogeneity are
      also analyzed.

PMID- 18345834
TI  - The acoustic and visual factors influencing the construction of tranquil space in
      urban and rural environments tranquil spaces-quiet places?
AB  - Prior to this work no structured mechanism existed in the UK to evaluate the
      tranquillity of open spaces with respect to the characteristics of both acoustic
      and visual stimuli. This is largely due to the fact that within the context of
      "tranquil" environments, little is known about the interaction of the audio
      visual modalities and how they combine to lead to the perception of tranquillity.
      This paper presents the findings of a study in which visual and acoustic data,
      captured from 11 English rural and urban landscapes, were used by 44 volunteers
      to make subjective assessments of both their perceived tranquillity of a
      location, and the loudness of five generic soundscape components. The results
      were then analyzed alongside objective measurements taken in the laboratory. It
      was found that the maximum sound pressure level (L(Amax)) and the percentage of
      natural features present at a location were the key factors influencing
      tranquillity. Engineering formulas for the tranquillity as a function of the
      noise level and proportion of the natural features are proposed.

PMID- 18345835
TI  - Evaluating airborne sound insulation in terms of speech intelligibility.
AB  - This paper reports on an evaluation of ratings of the sound insulation of
      simulated walls in terms of the intelligibility of speech transmitted through the
      walls. Subjects listened to speech modified to simulate transmission through 20
      different walls with a wide range of sound insulation ratings, with constant
      ambient noise. The subjects' mean speech intelligibility scores were compared
      with various physical measures to test the success of the measures as sound
      insulation ratings. The standard Sound Transmission Class (STC) and Weighted
      Sound Reduction Index ratings were only moderately successful predictors of
      intelligibility scores, and eliminating the 8 dB rule from STC led to very modest
      improvements. Various previously established speech intelligibility measures
      (e.g., Articulation Index or Speech Intelligibility Index) and measures derived
      from them, such as the Articulation Class, were all relatively strongly related
      to speech intelligibility scores. In general, measures that involved arithmetic
      averages or summations of decibel values over frequency bands important for
      speech were most strongly related to intelligibility scores. The two most
      accurate predictors of the intelligibility of transmitted speech were an
      arithmetic average transmission loss over the frequencies from 200 to 2.5 kHz and
      the addition of a new spectrum weighting term to R(w) that included frequencies
      from 400 to 2.5 kHz.

PMID- 18345836
TI  - Sound field separation technique based on equivalent source method and its
      application in nearfield acoustic holography.
AB  - A technique for separating sound fields using two closely spaced parallel
      measurement surfaces and based on equivalent source method is proposed. The
      method can separate wave components crossing two measurement surfaces in opposite
      directions, which makes nearfield acoustic holography (NAH) applications in a
      field where there exist sources on the two sides of the hologram surface, in a
      reverberant field or in a scattered field, possible. The method is flexible in
      applications, simple in computation, and very easy to implement. The measurement
      surfaces can be arbitrarily shaped, and they are not restricted to be regular as
      in the traditional field separation technique. And, because the method performs
      field separation calculations directly in the spatial domain-not in the wave
      number domain--it avoids the errors and limitations (the window effects, etc.)
      associated with the traditional field separation technique based on the spatial
      Fourier transform method. In the paper, a theoretical description is first given,
      and the performance of the proposed field separation technique and its
      application in NAH are then evaluated through experiments.

PMID- 18345837
TI  - Two-tone suppression of stimulus frequency otoacoustic emissions.
AB  - Stimulus frequency otoacoustic emissions (SFOAEs) measured using a suppressor
      tone in human ears are analogous to two-tone suppression responses measured
      mechanically and neurally in mammalian cochleae. SFOAE suppression was measured
      in 24 normal-hearing adults at octave frequencies (f(p)=0.5-8.0 kHz) over a 40 dB
      range of probe levels (L(p)). Suppressor frequencies (f(s)) ranged from -2.0 to
      0.7 octaves re: f(p), and suppressor levels ranged from just detectable
      suppression to full suppression. The lowest suppression thresholds occurred for
      "best" f(s) slightly higher than f(p). SFOAE growth of suppression (GOS) had
      slopes close to one at frequencies much lower than best f(s), and shallow slopes
      near best f(s), which indicated compressive growth close to 0.3 dBdB. Suppression
      tuning curves constructed from GOS functions were well defined at 1, 2, and 4
      kHz, but less so at 0.5 and 8.0 kHz. Tuning was sharper at lower L(p) with an
      equivalent rectangular bandwidth similar to that reported behaviorally for
      simultaneous masking. The tip-to-tail difference assessed cochlear gain,
      increasing with decreasing L(p) and increasing f(p) at the lowest L(p) from 32 to
      45 dB for f(p) from 1 to 4 kHz. SFOAE suppression provides a noninvasive measure
      of the saturating nonlinearities associated with cochlear amplification on the
      basilar membrane.

PMID- 18345838
TI  - Comparison between otoacoustic and auditory brainstem response latencies supports
      slow backward propagation of otoacoustic emissions.
AB  - Experimental measurements of the latency of transient evoked otoacoustic emission
      and auditory brainstem responses are compared, to discriminate between different
      cochlear models for the backward acoustic propagation of otoacoustic emissions.
      In most transmission-line cochlear models otoacoustic emissions propagate towards
      the base as a slow transverse traveling wave, whereas other models assume fast
      backward propagation via longitudinal compression waves in the fluid. Recently,
      sensitive measurements of the basilar membrane motion have cast serious doubts on
      the existence of slow backward traveling waves associated with distortion product
      otoacoustic emissions [He et al., Hear. Res. 228, 112-122 (2007)]. On the other
      hand, recent analyses of "Allen-Fahey" experiments suggest instead that the slow
      mechanism transports most of the otoacoustic energy [Shera et al., J. Acoust.
      Soc. Am. 122, 1564-1575 (2007)]. The two models can also be discriminated by
      comparing accurate estimates of the otoacoustic emission latency and of the
      auditory brainstem response latency. In this study, this comparison is done using
      human data, partly original, and partly from the literature. The results are
      inconsistent with fast otoacoustic propagation, and suggest that slow traveling
      waves on the basilar membrane are indeed the main mechanism for the backward
      propagation of the otoacoustic energy.

PMID- 18345839
TI  - Ear asymmetries in middle-ear, cochlear, and brainstem responses in human
      infants.
AB  - In 2004, Sininger and Cone-Wesson examined asymmetries in the signal-to-noise
      ratio (SNR) of otoacoustic emissions (OAE) in infants, reporting that distortion
      product (DP)OAE SNR was larger in the left ear, whereas transient-evoked (TE)OAE
      SNR was larger in the right. They proposed that cochlear and brainstem
      asymmetries facilitate development of brain-hemispheric specialization for sound
      processing. Similarly, in 2006 Sininger and Cone-Wesson described ear asymmetries
      mainly favoring the right ear in infant auditory brainstem responses (ABRs). The
      present study analyzed 2640 infant responses to further explore these effects.
      Ear differences in OAE SNR, signal, and noise were evaluated separately and
      across frequencies (1.5, 2, 3, and 4 kHz), and ABR asymmetries were compared with
      cochlear asymmetries. Analyses of ear-canal reflectance and admittance showed
      that asymmetries in middle-ear functioning did not explain cochlear and brainstem
      asymmetries. Current results are consistent with earlier studies showing right
      ear dominance for TEOAE and ABR. Noise levels were higher in the right ear for
      OAEs and ABRs, causing ear asymmetries in SNR to differ from those in signal
      level. No left-ear dominance for DPOAE signal was observed. These results do not
      support a theory that ear asymmetries in cochlear processing mimic hemispheric
      brain specialization for auditory processing.

PMID- 18345840
TI  - Inverted direction of wave propagation (IDWP) in the cochlea.
AB  - The "classical" view on wave propagation is that propagating waves are possible
      in both directions along the length of the basilar membrane and that they have
      identical properties. Results of several recently executed experiments [T. Ren,
      Nat. Neurosci. 2, 333-334 (2004) and W. X. He, A. L. Nuttall, and T. Ren, Hear.
      Res., 228, 112-122 (2007)] appear to contradict this view. In the current work
      measurements were made of the velocity of the guinea-pig basilar membrane (BM).
      Distortion products (DPs) were produced by presenting two primary tones, with
      frequencies below the characteristic frequency f(0) of the BM location at which
      the BM measurements were made, with a constant frequency ratio. In each
      experiment the phase of the principal DP, with frequency 2f(1)-f(2), was recorded
      as a function of the DP frequency. The results indicate that the DP wave going
      from the two-tone interaction region toward the stapes is not everywhere
      traveling in the reverse direction, but also in the forward direction. The extent
      of the region in which the forward wave occurs appears larger than is accounted
      for by classical theory. This property has been termed "inverted direction of
      wave propagation." The results of this study confirm the wave propagation
      findings of other authors. The experimental data are compared to theoretical
      predictions for a classical three-dimensional model of the cochlea that is based
      on noise-response data of the same animal. Possible physical mechanisms
      underlying the findings are discussed.

PMID- 18345842
TI  - A variant temporal-masking-curve method for inferring peripheral auditory
      compression.
AB  - Recent studies have suggested that the degree of on-frequency peripheral auditory
      compression is similar for apical and basal cochlear sites and that compression
      extends to a wider range of frequencies in apical than in basal sites. These
      conclusions were drawn from the analysis of the slopes of temporal masking curves
      (TMCs) on the assumption that forward masking decays at the same rate for all
      probe and masker frequencies. The aim here was to verify this conclusion using a
      different assumption. TMCs for normal hearing listeners were measured for probe
      frequencies (f(P)) of 500 and 4000 Hz and for masker frequencies (f(M)) of 0.4,
      0.55, and 1.0 times the probe frequency. TMCs were measured for probes of 9 and
      15 dB sensation level. The assumption was that given a 6 dB increase in probe
      level, linear cochlear responses to the maskers should lead to a 6 dB vertical
      shift of the corresponding TMCs, while compressive responses should lead to
      bigger shifts. Results were consistent with the conclusions from earlier studies.
      It is argued that this supports the assumptions of the standard TMC method for
      inferring compression, at least in normal-hearing listeners.

PMID- 18345841
TI  - Forward-masked spatial tuning curves in cochlear implant users.
AB  - Forward-masked psychophysical spatial tuning curves (fmSTCs) were measured in
      twelve cochlear-implant subjects, six using bipolar stimulation (Nucleus devices)
      and six using monopolar stimulation (Clarion devices). fmSTCs were measured at
      several probe levels on a middle electrode using a fixed-level probe stimulus and
      variable-level maskers. The average fmSTC slopes obtained in subjects using
      bipolar stimulation (3.7 dBmm) were approximately three times steeper than
      average slopes obtained in subjects using monopolar stimulation (1.2 dBmm).
      Average spatial bandwidths were about half as wide for subjects with bipolar
      stimulation (2.6 mm) than for subjects with monopolar stimulation (4.6 mm). None
      of the tuning curve characteristics changed significantly with probe level.
      fmSTCs replotted in terms of acoustic frequency, using Greenwood's [J. Acoust.
      Soc. Am. 33, 1344-1356 (1961)] frequency-to-place equation, were compared with
      forward-masked psychophysical tuning curves obtained previously from normal
      hearing and hearing-impaired acoustic listeners. The average tuning
      characteristics of fmSTCs in electric hearing were similar to the broad tuning
      observed in normal-hearing and hearing-impaired acoustic listeners at high
      stimulus levels. This suggests that spatial tuning is not the primary factor
      limiting speech perception in many cochlear implant users.

PMID- 18345843
TI  - Role of attention in overshoot: frequency certainty versus uncertainty.
AB  - Overshoot, the elevation in the threshold for a brief signal that comes on close
      to masker onset, was measured with signal frequency certain (same frequency on
      every trial) or uncertain (randomized over trials). In broadband noise,
      thresholds were higher 2 ms after masker onset than 200 ms later, by 9 dB with
      frequency certainty, by 6-7 dB with uncertainty. In narrowband noise centered on
      the signal frequency, thresholds at 2 ms were not elevated with certainty, but
      were elevated 4-5 dB with uncertainty. Thus, frequency uncertainty leads to less
      overshoot in broadband noise, to more overshoot in narrowband noise. Reduced
      overshoot in broadband noise may come about because the masker, given its many
      frequencies, disrupts focusing at onset as much under certainty as uncertainty.
      Once the initial disruption dissipates, threshold is lower with certainty so
      overshoot is greater. In contrast, a narrowband noise with frequencies only near
      the signal does not disrupt focusing when the signal frequency is known
      beforehand, so overshoot is absent. When frequency is uncertain, the narrowband
      noise serves to focus attention on the signal frequency; as this requires time,
      detection near noise onset is poorer than later on, so overshoot is present.

PMID- 18345844
TI  - Contributions of talker characteristics and spatial location to auditory
      streaming.
AB  - To examine whether auditory streaming contributes to unmasking, intelligibility
      of target sentences against two competing talkers was measured using the
      coordinate response measure (CRM) [Bolia et al., J. Acoust. Soc. Am. 107, 1065
      1066 (2007)] corpus. In the control condition, the speech reception threshold
      (50% correct) was measured when the target and two maskers were collocated
      straight ahead. Separating maskers from the target by +/-30 degrees resulted in
      spatial release from masking of 12 dB. CRM sentences involve an identifier in the
      first part and two target words in the second part. In experimental conditions,
      masking talkers started spatially separated at +/-30 degrees but became
      collocated with the target before the scoring words. In one experiment, one
      target and two different maskers were randomly selected from a mixed-sex corpus.
      Significant unmasking of 4 dB remained despite the absence of persistent location
      cues. When same-sex talkers were used as maskers and target, unmasking was
      reduced. These data suggest that initial separation may permit confident
      identification and streaming of the target and masker speech where significant
      differences between target and masker voice characteristics exist, but where
      target and masker characteristics are similar, listeners must rely more heavily
      on continuing spatial cues.

PMID- 18345845
TI  - The mid-difference hump in forward-masked intensity discrimination.
AB  - Forward-masked intensity-difference limens (DLs) for pure-tone standards
      presented at low, medium, and high levels were obtained for a wide range of
      masker-standard level differences. At a standard level of 25 dB SPL, the masker
      had a significant effect on intensity resolution, and the data showed a mid
      difference hump: The DL elevation was greater at intermediate than at large
      masker-standard level differences. These results support the hypothesis that the
      effect of a forward masker on intensity resolution is modulated by the similarity
      between the masker and the standard. For a given masker-standard level
      difference, the effect of the masker on the DL was larger for a 55-dB SPL than
      for the 25-dB SPL standard, providing new support for a midlevel hump. To examine
      whether the masker-induced DL elevations are related to masker-induced loudness
      changes [R. P. Carlyon and H. A. Beveridge, J. Acoust. Soc. Am. 93, 2886-2895
      (1993)], the effect of the masker on target loudness was measured for the same
      listeners. Loudness enhancement followed a mid-difference hump pattern at both
      the low and the intermediate target level. The correlation between loudness
      changes and DL elevations was significant, but several aspects of the data are
      incompatible with the predicted one-on-one relation between the two effects.

PMID- 18345846
TI  - Acoustic model adaptation for ortolan bunting (Emberiza hortulana L.) song-type
      classification.
AB  - Automatic systems for vocalization classification often require fairly large
      amounts of data on which to train models. However, animal vocalization data
      collection and transcription is a difficult and time-consuming task, so that it
      is expensive to create large data sets. One natural solution to this problem is
      the use of acoustic adaptation methods. Such methods, common in human speech
      recognition systems, create initial models trained on speaker independent data,
      then use small amounts of adaptation data to build individual-specific models.
      Since, as in human speech, individual vocal variability is a significant source
      of variation in bioacoustic data, acoustic model adaptation is naturally suited
      to classification in this domain as well. To demonstrate and evaluate the
      effectiveness of this approach, this paper presents the application of maximum
      likelihood linear regression adaptation to ortolan bunting (Emberiza hortulana
      L.) song-type classification. Classification accuracies for the adapted system
      are computed as a function of the amount of adaptation data and compared to
      caller-independent and caller-dependent systems. The experimental results
      indicate that given the same amount of data, supervised adaptation significantly
      outperforms both caller-independent and caller-dependent systems.

PMID- 18345847
TI  - Investigation of perceptual constancy in the temporal-envelope domain.
AB  - The ability to discriminate complex temporal envelope patterns submitted to
      temporal compression or expansion was assessed in normal-hearing listeners. An
      XAB, matching-to-sample-procedure was used. X, the reference stimulus, is
      obtained by applying the sum of two, inharmonically related, sinusoids to a
      broadband noise carrier. A and B are obtained by multiplying the frequency of
      each modulation component of X by the same time expansion/compression factor,
      alpha (alphain[0.35-2.83]). For each trial, A or B is a time-reversed rendering
      of X, and the listeners' task is to choose which of the two is matched by X.
      Overall, the results indicate that discrimination performance degrades for
      increasing amounts of time expansion/compression (i.e., when alpha departs from
      1), regardless of the frequency spacing of modulation components and the peak-to
      trough ratio of the complex envelopes. An auditory model based on envelope
      extraction followed by a memory-limited, template-matching process accounted for
      results obtained without time scaling of stimuli, but generally underestimated
      discrimination ability with either time expansion or compression, especially with
      the longer stimulus durations. This result is consistent with partial or
      incomplete perceptual normalization of envelope patterns.

PMID- 18345848
TI  - Detection of combined changes in interaural time and intensity differences:
      Segregated mechanisms in cue type and in operating frequency range?
AB  - Although physiological studies have revealed segregated binaural pathways, namely
      the medial and lateral superior olives, it is unclear whether the human auditory
      system has separate mechanisms for different cue types (interaural time and
      intensity differences; ITD and IID, respectively) and for operating frequency
      ranges. This study hypothesized "channels" for ITD and IID processing, and
      examined channel interaction at low and high frequencies based on the signal
      detection theory. The stimuli were a 125- or 500-Hz tone and a 4-kHz tone
      amplitude-modulated with a half-wave-rectified 125-Hz sinusoid, presented
      dichotically with various baseline ITDs and IIDs. The detectability indices,
      d('), for ITD and IID changes, imposed individually or simultaneously in the same
      direction, were derived from the results of a forced-choice task. The degree of
      channel interaction was estimated by comparing d(') for combined cues with those
      for individual cues. The estimated interaction showed little effect of baseline
      ITD or IID. The results generally exhibited nonzero interaction, indicating that
      the cue processes are not completely independent. The interaction was stronger
      for high frequencies than for low frequencies. The results can be interpreted as
      indicating the involvement of different binaural mechanisms for different
      frequency regions.

PMID- 18345849
TI  - Adaptive feedback cancellation in hearing aids with clipping in the feedback
      path.
AB  - Adaptive linear filtering algorithms are commonly used to cancel feedback in
      hearing aids. The use of these algorithms is based on the assumption that the
      feedback path is linear, so nonlinearities in the feedback path may affect
      performance. This study investigated the effect on feedback canceller performance
      of clipping of the feedback signal arriving at the microphone, as well as the
      benefit of applying identical clipping to the cancellation signal so that the
      cancellation path modeled the nonlinearity of the feedback path. Feedback signal
      clipping limited the amount of added stable gain that the feedback canceller
      could provide, and caused misadjustment in response to high-level inputs, by
      biasing adaptive filter coefficients toward lower magnitudes. Cancellation signal
      clipping mitigated these negative effects, permitting higher amounts of added
      stable gain and less misadjustment in response to high-level inputs, but the
      benefit was reduced in the presence of the highest-level inputs.

PMID- 18345850
TI  - A biphasic theory for the viscoelastic behaviors of vocal fold lamina propria in
      stress relaxation.
AB  - In this study, a biphasic theory is applied to investigate the viscoelastic
      behaviors of vocal fold lamina propria during stress relaxation. The vocal fold
      lamina propria tissue is described as a biphasic material composed of a solid
      phase and an interstitial fluid phase. The biphasic theory reveals the
      interaction between the solid and the fluid. For the one-dimensional case, the
      analytical solutions of solid displacement, fluid velocity, and stress are
      derived. The biphasic theory predicts the stress relaxation of the vocal fold
      lamina propria. The quasilinear viscoelastic model as well as its higher-order
      elastic parameters can be derived from this biphasic theory. Furthermore, the
      fluid is found to support the majority of the stress at the early stage of stress
      relaxation; however, when the time becomes sufficiently large, the solid
      eventually bears all the stress. The early fluid stress support is much higher
      than the eventual solid support and may be important for understanding the
      effects of dehydration on tissue damage. By considering the solid-fluid structure
      of the vocal fold lamina propria, the biphasic theory allows for a more physical
      theory of tissue viscoelasticity than a single phase solid description and may
      provide a valuable physical mechanism for the observed vocal fold rheologic
      behaviors.

PMID- 18345851
TI  - The phonation critical condition in rectangular glottis with wide prephonatory
      gaps.
AB  - The effect of the pressure recovery at glottal exit is introduced to modify the
      one-mass model. Using the modified one-mass model, the phonation critical
      condition, including phonation threshold pressure and phonation threshold flow,
      is analyzed by using the small-amplitude oscillation theory. It is found that the
      phonation threshold pressure is not sensitive to the change of the prephonatory
      glottal width at a wide glottal gap. This result agrees with previous
      experimental observations and suggests that the low slope of dependence of
      phonation threshold pressure on prephonatory gap found by Chan and Titze [J.
      Acoust. Soc. Am. 119, 2351-2362 (2006)] could be a consequence of the pressure
      recovery effect at the glottal exit. In addition, it is predicted that the
      phonation threshold flow is always significantly increased with the prephonatory
      gap even at a wide prephonatory glottal gap. Therefore, the phonation threshold
      flow has an advantage in assessing the phonatory system at a wide prephonatory
      gap in comparison with the phonation threshold pressure. The phonation threshold
      flow can be a useful aerodynamic parameter for pathological conditions in which
      the incomplete glottal gap is often seen.

PMID- 18345852
TI  - Investigation of a glottal related harmonics-to-noise ratio and spectral tilt as
      indicators of glottal noise in synthesized and human voice signals.
AB  - The harmonics-to-noise ratio (HNR) of the voiced speech signal has implicitly
      been used to infer information regarding the turbulent noise level at the
      glottis. However, two problems exist for inferring glottal noise attributes from
      the HNR of the speech wave form: (i) the measure is fundamental frequency (f0)
      dependent for equal levels of glottal noise, and (ii) any deviation from signal
      periodicity affects the ratio, not just turbulent noise. An alternative harmonics
      to-noise ratio formulation [glottal related HNR (GHNR')] is proposed to overcome
      the former problem. In GHNR' a mean over the spectral range of interest of the
      HNRs at specific harmonic/between-harmonic frequencies (expressed in linear
      scale) is calculated. For the latter issue [(ii)] two spectral tilt measures are
      shown, using synthesis data, to be sensitive to glottal noise while at the same
      time being comparatively insensitive to other glottal aperiodicities. The
      theoretical development predicts that the spectral tilt measures reduce as noise
      levels increase. A conventional HNR estimator, GHNR' and two spectral tilt
      measures are applied to a data set of 13 pathological and 12 normal voice
      samples. One of the tilt measures and GHNR' are shown to provide statistically
      significant differentiating power over a conventional HNR estimator.

PMID- 18345853
TI  - Development and evaluation of methods for assessing tone production skills in
      Mandarin-speaking children with cochlear implants.
AB  - The aim of the study was (1) to develop methods for evaluating tone production of
      children with cochlear implants (CIs) who speak Mandarin Chinese and (2) to
      evaluate the efficacy of using these methods to assess tone production. The
      subjects included two groups of native-Mandarin-Chinese-speaking children: 14
      prelingually deafened children who had received CIs and 61 normal-hearing (NH)
      children as controls. The acoustic analysis focused on quantification of the
      degree of differentiation among lexical tones based on tonal ellipses and the
      overall similarity of tone contours produced by the children with CIs to
      normative contours derived from the 61 NH children. An artificial neural network
      was used to recognize tones produced by the children with CIs after trained with
      tone tokens produced by the NH children. Finally, perceptual judgments on the
      tone production of both groups were obtained from eight native-Mandarin-speaking
      NH adults to evaluate the efficacy of the methods. The results showed that all
      measures using the acoustic, neural-network, and perceptual analyses were highly
      correlated with each other and could be used to effectively evaluate tone
      production of children with CIs.

PMID- 18345854
TI  - Selectivity of modulation interference for consonant identification in normal
      hearing listeners.
AB  - The present study sought to establish whether speech recognition can be disrupted
      by the presence of amplitude modulation (AM) at a remote spectral region, and
      whether that disruption depends upon the rate of AM. The goal was to determine
      whether this paradigm could be used to examine which modulation frequencies in
      the speech envelope are most important for speech recognition. Consonant
      identification for a band of speech located in either the low- or high-frequency
      region was measured in the presence of a band of noise located in the opposite
      frequency region. The noise was either unmodulated or amplitude modulated by a
      sinusoid, a band of noise with a fixed absolute bandwidth, or a band of noise
      with a fixed relative bandwidth. The frequency of the modulator was 4, 16, 32, or
      64 Hz. Small amounts of modulation interference were observed for all modulator
      types, irrespective of the location of the speech band. More important, the
      interference depended on modulation frequency, clearly supporting the existence
      of selectivity of modulation interference with speech stimuli. Overall, the
      results suggest a primary role of envelope fluctuations around 4 and 16 Hz
      without excluding the possibility of a contribution by faster rates.

PMID- 18345855
TI  - Factors influencing intelligibility of ideal binary-masked speech: implications
      for noise reduction.
AB  - The application of the ideal binary mask to an auditory mixture has been shown to
      yield substantial improvements in intelligibility. This mask is commonly applied
      to the time-frequency (T-F) representation of a mixture signal and eliminates
      portions of a signal below a signal-to-noise-ratio (SNR) threshold while allowing
      others to pass through intact. The factors influencing intelligibility of ideal
      binary-masked speech are not well understood and are examined in the present
      study. Specifically, the effects of the local SNR threshold, input SNR level,
      masker type, and errors introduced in estimating the ideal mask are examined.
      Consistent with previous studies, intelligibility of binary-masked stimuli is
      quite high even at -10 dB SNR for all maskers tested. Performance was affected
      the most when the masker dominated T-F units were wrongly labeled as target
      dominated T-F units. Performance plateaued near 100% correct for SNR thresholds
      ranging from -20 to 5 dB. The existence of the plateau region suggests that it is
      the pattern of the ideal binary mask that matters the most rather than the local
      SNR of each T-F unit. This pattern directs the listener's attention to where the
      target is and enables them to segregate speech effectively in multitalker
      environments.

PMID- 18345856
TI  - Acoustical measurements of expression devices in pipe organs.
AB  - In this investigation, three different swell systems known in pipe organs, the
      swell box, the crescendo wheel, and the historic wind swell were measured and
      compared to each other. The dynamic range of the crescendo wheel was found to be
      most effective, and for frequencies near 2 kHz the increase in sound pressure
      level could be up to 50 dB between the softest and the loudest adjustment. The
      maximum dynamic range for the wind swell and the swell box were found to be 10-20
      dB in the same frequency range. With its step-wise crescendo procedure, the
      crescendo wheel simulates the type of orchestra crescendo which is reached by
      successively adding further musical instruments. In contrast, the swell box and
      the wind swell produce a crescendo effect similar to the crescendo in which
      individual musical instruments perform a dynamic movement. This type of crescendo
      requires a continuous level increase but allows a smaller dynamic range. The
      disappearance of the wind swell is not surprising because it offers no advantage
      over the swell box, while being restricted to stops with free reeds.

PMID- 18345857
TI  - Fast wave ultrasonic propagation in trabecular bone: numerical study of the
      influence of porosity and structural anisotropy.
AB  - Our goal is to assess the potential of computational methods as an alternative to
      analytical models to predict the two longitudinal wave modes observed in
      cancellous bone and predicted by the Biot theory. A three-dimensional (3D) finite
      difference time-domain method is coupled with 34 human femoral trabecular
      microstructures measured using microcomputed tomography. The main trabecular
      alignment (MTA) and the degree of anisotropy (DA) were assessed for all samples.
      DA values were comprised between 1.02 and 1.9. The influence of bone volume
      fraction (BV/TV) between 5% and 25% on the properties of the fast and slow waves
      was studied using a dedicated image processing algorithm to modify the initial 3D
      microstructures. A heuristic method was devised to determine when both wave modes
      are time separated. The simulations (performed in three perpendicular directions)
      predicted that both waves generally overlap in time for a direction of
      propagation perpendicular to the MTA. When these directions are parallel, both
      waves are separated in time for samples with high DA and BV/TV values. A
      relationship was found between the least bone volume fraction required for the
      observation of nonoverlapping waves and the degree of anisotropy: The higher the
      DA, the lower the least BV/TV.

PMID- 18345858
TI  - Characterization of high intensity focused ultrasound transducers using acoustic
      streaming.
AB  - A new approach for characterizing high intensity focused ultrasound (HIFU)
      transducers is presented. The technique is based upon the acoustic streaming
      field generated by absorption of the HIFU beam in a liquid medium. The streaming
      field is quantified using digital particle image velocimetry, and a numerical
      algorithm is employed to compute the acoustic intensity field giving rise to the
      observed streaming field. The method as presented here is applicable to moderate
      intensity regimes, above the intensities which may be damaging to conventional
      hydrophones, but below the levels where nonlinear propagation effects are
      appreciable. Intensity fields and acoustic powers predicted using the streaming
      method were found to agree within 10% with measurements obtained using
      hydrophones and radiation force balances. Besides acoustic intensity fields, the
      streaming technique may be used to determine other important HIFU parameters,
      such as beam tilt angle or absorption of the propagation medium.

PMID- 18345859
TI  - An ecological acoustic recorder (EAR) for long-term monitoring of biological and
      anthropogenic sounds on coral reefs and other marine habitats.
AB  - Keeping track of long-term biological trends in many marine habitats is a
      challenging task that is exacerbated when the habitats in question are in remote
      locations. Monitoring the ambient sound field may be a useful way of assessing
      biological activity because many behavioral processes are accompanied by sound
      production. This article reports the preliminary results of an effort to develop
      and use an Ecological Acoustic Recorder (EAR) to monitor biological activity on
      coral reefs and in surrounding waters for periods of 1 year or longer. The EAR is
      a microprocessor-based autonomous recorder that periodically samples the ambient
      sound field and also automatically detects sounds that meet specific criteria.
      The system was used to record the sound field of coral reefs and other marine
      habitats on Oahu, HI. Snapping shrimp produced the dominant acoustic energy on
      the reefs examined and exhibited clear diel acoustic trends. Other biological
      sounds recorded included those produced by fish and cetaceans, which also
      exhibited distinct temporal variability. Motor vessel activity could also be
      monitored effectively with the EAR. The results indicate that acoustic monitoring
      may be an effective means of tracking biological and anthropogenic activity at
      locations where continuous monitoring by traditional survey methods is
      impractical.

PMID- 18345860
TI  - Vocal learning in Budgerigars (Melopsittacus undulatus): effects of an acoustic
      reference on vocal matching.
AB  - Budgerigars were trained to produce specific vocalizations (calls) using operant
      conditioning and food reinforcement. The bird's call was compared to a digital
      representation of the call stored in a computer to determine a match. Once birds
      were responding at a high level of precision, we measured the effect of several
      manipulations upon the accuracy and the intensity of call production. Also, by
      differentially reinforcing other aspects of vocal behavior, budgerigars were
      trained to produce a call that matched another bird's contact call and to alter
      the latency of their vocal response. Both the accuracy of vocal matching and the
      intensity level of vocal production increased significantly when the bird could
      hear the template immediately before each trial. Moreover, manipulating the delay
      between the presentation of an acoustic reference and the onset of vocal
      production did not significantly affect either vocal intensity or matching
      accuracy. Interestingly, the vocalizations learned and reinforced in these
      operant experiments were only occasionally used in more natural communicative
      situations, such as when birds called back and forth to one another in their home
      cages.

PMID- 18345861
TI  - Vocalizations produced by humpback whale (Megaptera novaeangliae) calves recorded
      in Hawaii.
AB  - Although humpback whale (Megaptera novaeangliae) calves are reported to vocalize,
      this has not been measurably verified. During March 2006, an underwater video
      camera and two-element hydrophone array were used to record nonsong vocalizations
      from a mother-calf escort off Hawaii. Acoustic data were analyzed; measured time
      delays between hydrophones provided bearings to 21 distinct vocalizations
      produced by the male calf. Signals were pulsed (71%), frequency modulated (19%),
      or amplitude modulated (10%). They were of simple structure, low frequency
      (mean=220 Hz), brief duration (mean=170 ms), and relatively narrow bandwidth
      (mean=2 kHz). The calf produced three series of "grunts" when approaching the
      diver. During winters of the years 2001-2005 in Hawaii, nonsong vocalizations
      were recorded in 109 (65%) of 169 groups with a calf using an underwater video
      and single (omnidirectional) hydrophone. Nonsong vocalizations were most common
      (34 of 39) in lone mother-calf pairs. A subsample from this dataset of 60 signals
      assessed to be vocalizations provided strong evidence that 10 male and 18 female
      calves vocalized based on statistical similarity to the 21 verified calf signals,
      proximity to an isolated calf (27 of 28 calves), strong signal-to-noise ratio,
      and/or bubble emissions coincident to sound.

PMID- 18345862
TI  - Variation in call pitch among killer whale ecotypes.
AB  - Vocal structure can vary between populations due to variation in ecology
      dependent selection pressures, such as masking by background noise and the
      presence of eavesdroppers. Signalers can overcome these obstacles to effective
      communication by avoiding frequencies that overlap with background noise or the
      audible range of eavesdroppers. In the Northeastern Pacific three "ecotypes" of
      killer whale coexist in sympatry, but differ from one another in their diet and
      habitat use. The minimum frequency (F(min)) and the frequency containing the peak
      energy between 0 and 10 kHz (F(peak)) of a random sample of calls produced by a
      population of each ecotype was measured. The offshore ecotype produced calls with
      a significantly higher F(min) than the other ecotypes, which could be a strategy
      to avoid masking by low frequency chronic bandlimited wind noise found in the
      offshore environment. The resident ecotype produced calls with a significantly
      higher F(min) and F(peak) than the transient ecotype. This could be to reduce
      detection by their salmonid prey, which has a narrow band, low frequency auditory
      range.

PMID- 18345863
TI  - Classification of broadband echoes from prey of a foraging Blainville's beaked
      whale.
AB  - Blainville's beaked whales (Mesoplodon densirostris) use broadband, ultrasonic
      echolocation signals with a -10 dB bandwidth from 26 to 51 kHz to search for,
      localize, and approach prey that generally consist of mid-water and deep-water
      fishes and squid. Although it is well known that the spectral characteristics of
      broadband echoes from marine organisms vary as a function of size, shape,
      orientation, and anatomical group, there is little evidence as to whether or not
      free-ranging toothed whales use spectral cues in discriminating between prey and
      nonprey. In order to study the prey-classification process, a stereo acoustic tag
      was deployed on a Blainville's beaked whale so that emitted clicks and the
      corresponding echoes from targets in the water could be recorded. A comparison of
      echoes from targets apparently selected by the whale and those from a sample of
      scatterers that were not selected suggests that spectral features of the echoes,
      target strengths, or both may have been used by the whale to discriminate between
      echoes. Specifically, the whale appears to favor targets with one or more nulls
      in the echo spectra and to seek prey with higher target strengths at deeper
      depths.

PMID- 18345864
TI  - Methods for automatically analyzing humpback song units.
AB  - This paper presents mathematical techniques for automatically extracting and
      analyzing bioacoustic signals. Automatic techniques are described for isolation
      of target signals from background noise, extraction of features from target
      signals and unsupervised classification (clustering) of the target signals based
      on these features. The only user-provided inputs, other than raw sound, is an
      initial set of signal processing and control parameters. Of particular note is
      that the number of signal categories is determined automatically. The techniques,
      applied to hydrophone recordings of humpback whales (Megaptera novaeangliae),
      produce promising initial results, suggesting that they may be of use in
      automated analysis of not only humpbacks, but possibly also in other bioacoustic
      settings where automated analysis is desirable.

PMID- 18345865
TI  - Feasibility of ultrasound phase contrast for heating localization.
AB  - Ultrasound-based methods for temperature monitoring could greatly assist focused
      ultrasound visualization and treatment planning based on sound speed-induced
      change in phase as a function of temperature. A method is presented that uses
      reflex transmission integration, planar projection, and tomographic
      reconstruction techniques to visualize phase contrast by measuring the sound
      field before and after heat deposition. Results from experiments and numerical
      simulations employing a through-transmission setup are presented to demonstrate
      feasibility of using phase contrast methods for identifying temperature change. A
      1.088-MHz focused transducer was used to interrogate a medium with a phase
      contrast feature, following measurement of the baseline reference field with a
      hydrophone. A thermal plume in water and a tissue phantom with multiple water
      columns was used in separate experiments to produce a phase contrast. The
      reference and phase contrast field scans were numerically backprojected and the
      phase difference correctly identified the position and orientation of the
      features. The peak temperature reconstructed from the phase shift was within 0.2
      degrees C of the measured temperature in the plume. Simulated results were in
      good agreement with experimental results. Finally, employment of reflex
      transmission imaging techniques for adopting a pulse-echo arrangement was
      simulated, and its future experimental application is discussed.

PMID- 18345866
TI  - Interaction of microbubbles with high intensity pulsed ultrasound.
AB  - High intensity pulsed ultrasound, interacting with microbubble contrast agents,
      is potentially useful for drug delivery, cancer treatment, and tissue ablation,
      among other applications. To establish the fundamental understanding on the
      interaction of a microbubble (in an infinite volume of water) with an ultrasound
      pressure field, a numerical study is performed using the boundary element method.
      The response of the bubble, in terms of its shape at different times, the maximum
      bubble radius obtained, the oscillation time, the jet velocity, and its
      translational movement, is studied. The effect of ultrasound intensity and
      initial bubble size is examined as well. One important outcome is the
      determination of the conditions under which a clear jet will be formed in a
      microbubble in its interaction with a specific sound wave. The high speed jet is
      crucial for the aforementioned intended applications.

PMID- 18345867
TI  - In vivo ultrasonic attenuation slope estimates for detecting cervical ripening in
      rats: Preliminary results.
AB  - To effectively postpone preterm birth, cervical ripening needs to be detected and
      delayed. As the cervix ripens, the spacing between the collagen fibers increases
      and fills with water, hyaluronan, decorin, and enzymes suggesting that the
      ultrasonic attenuation of the cervix should decrease. The decrease in ultrasonic
      attenuation may be detectable, leading to an effective means of detecting
      cervical ripening. Herein, the traditional attenuation slope-estimation algorithm
      based on measuring the downshift in center frequency of the ultrasonic
      backscattered signal with propagation depth was modified and applied to the
      cervix of rats. The modified algorithm was verified using computer simulations
      and an ex vivo tissue sample before being evaluated in in vivo animal studies.
      Spherically-focused f/3 transducers with 33-MHz center frequencies and with 9-mm
      focal lengths were used in both the simulations and experiments. The accuracy was
      better than 15% in the simulations, and the attenuation slope of the cervix in
      the ex vivo experiment was 2.6+/-0.6 dB/cm-MHz, which is comparable to 2.5+/-0.4
      dB/cm-MHz measured using a through-transmission insertion loss technique. For the
      in vivo experiments, a statistically significant effect of ultrasonic attenuation
      with gestational age was not observed. The large variances in the in vivo results
      were most likely due to the natural variation in attenuation for biological
      tissue between animals.

PMID- 18345869
TI  - Electrophoretic size separation of particles in a periodically constricted
      microchannel.
AB  - The size separation of Brownian particles with the same free mobility in an
      electrophoretic microchannel with alternating thick regions and narrow
      constrictions is studied theoretically. The electrophoretic mobility is field
      dependent and generally increases with field strength. In weak fields, Brownian
      diffusion dominates and the migration is controlled by the entrance effect.
      Therefore, smaller particles migrate faster than larger ones. In strong fields,
      however, the particle tends to follow electric field lines. Smaller particles are
      susceptible to Brownian motion and thus influenced by the nonuniform electric
      field in the well significantly. As a result, larger particles possess higher
      mobilities. Our simulation results agree with the experimental observations and
      provide guidance for efficient nanofluidic separation.

PMID- 18345870
TI  - NMR chemical shifts of molecules encapsulated in single walled carbon nanotubes.
AB  - We present density functional theory calculations of the nuclear magnetic
      resonance spectroscopy of molecules encapsulated within single walled carbon
      nanotubes. Ring currents in the nanotube induce shifts in the chemical shift of
      the nuclei comprising the encapsulated molecule. These changes in the chemical
      shifts are shown to have characteristic dependence on the chirality of the
      surrounding nanotubes.

PMID- 18345871
TI  - A fully relativistic method for calculation of nuclear magnetic shielding tensors
      with a restricted magnetically balanced basis in the framework of the matrix
      Dirac-Kohn-Sham equation.
AB  - A new relativistic four-component density functional approach for calculations of
      NMR shielding tensors has been developed and implemented. It is founded on the
      matrix formulation of the Dirac-Kohn-Sham (DKS) method. Initially, unperturbed
      equations are solved with the use of a restricted kinetically balanced basis set
      for the small component. The second-order coupled perturbed DKS method is then
      based on the use of restricted magnetically balanced basis sets for the small
      component. Benchmark relativistic calculations have been carried out for the (1)H
      and heavy-atom nuclear shielding tensors of the HX series (X=F,Cl,Br,I), where
      spin-orbit effects are known to be very pronounced. The restricted magnetically
      balanced basis set allows us to avoid additional approximations and/or strong
      basis set dependence which arises in some related approaches. The method provides
      an attractive alternative to existing approximate two-component methods with
      transformed Hamiltonians for relativistic calculations of chemical shifts and
      spin-spin coupling constants of heavy-atom systems. In particular, no picture
      change effects arise in property calculations.

PMID- 18345872
TI  - Finding reaction paths using the potential energy as reaction coordinate.
AB  - The intrinsic reaction coordinate curve (IRC), normally proposed as a
      representation of a reaction path, is parametrized as a function of the potential
      energy rather than the arc-length. This change in the parametrization of the
      curve implies that the values of the energy of the potential energy surface
      points, where the IRC curve is located, play the role of reaction coordinate. We
      use Caratheodory's relation to derive in a rigorous manner the proposed
      parametrization of the IRC path. Since this Caratheodory's relation is the basis
      of the theory of calculus of variations, then this fact permits to reformulate
      the IRC model from this mathematical theory. In this mathematical theory, the
      character of the variational solution (either maximum or minimum) is given
      through the Weierstrass E-function. As proposed by Crehuet and Bofill [J. Chem.
      Phys. 122, 234105 (2005)], we use the minimization of the Weierstrass E-function,
      as a function of the potential energy, to locate an IRC path between two minima
      from an arbitrary curve on the potential energy surface, and then join these two
      minima. We also prove, from the analysis of the Weierstrass E-function, the
      mathematical bases for the algorithms proposed to locate the IRC path. The
      proposed algorithm is applied to a set of examples. Finally, the algorithm is
      used to locate a discontinuous, or broken, IRC path, namely, when the path
      connects two first order saddle points through a valley-ridged inflection point.

PMID- 18345873
TI  - Pseudospectral time-dependent density functional theory.
AB  - Time-dependent density functional theory (TDDFT) is implemented within the Tamm
      Dancoff approximation (TDA) using a pseudospectral approach to evaluate two
      electron repulsion integrals. The pseudospectral approximation uses a split
      representation with both spectral basis functions and a physical space grid to
      achieve a reduction in the scaling behavior of electronic structure methods. We
      demonstrate here that exceptionally sparse grids may be used in the excitation
      energy calculation, following earlier work employing the pseudospectral
      approximation for determining correlation energies in wavefunction-based methods
      with similar conclusions. The pseudospectral TDA-TDDFT method is shown to be up
      to ten times faster than a conventional algorithm for hybrid functionals without
      sacrificing chemical accuracy.

PMID- 18345874
TI  - Relation between exchange-only optimized potential and Kohn-Sham methods with
      finite basis sets, and effect of linearly dependent products of orbital basis
      functions.
AB  - Recently, Staroverov, Scuseria, and Davidson [J. Chem. Phys. 124, 141103 (2006)]
      presented examples of exchange-only optimized effective potential (xOEP)
      calculations that yield exactly the Hartree-Fock (HF) total energy. Here,
      building on their work, arguments showing under which conditions xOEP methods,
      with finite basis sets, do or do not yield the HF ground state energy but a
      higher one, are given. While the orbital products of a complete basis are
      linearly dependent, the HF ground state energy can only be obtained via a finite
      basis set xOEP scheme in the case that all products of occupied and unoccupied
      orbitals emerging from the employed orbital basis set are linearly independent of
      each other. Further, exchange potentials leading to the HF ground state energy
      likely exhibit unphysical oscillations and do not represent a Kohn-Sham (KS)
      exchange potential as a functional derivative of the exchange energy. These
      findings appear to explain the seemingly paradoxical results of Staroverov et al.
      that certain finite basis set xOEP calculations lead to the HF ground state
      energy despite the fact that within a real space (or complete basis)
      representation, the xOEP ground state energy is always higher than the HF energy.
      Moreover, independent of whether or not the occupied and unoccupied orbital
      products are linearly dependent, it is shown that finite basis set xOEP methods
      only represent exact exchange-only (EXX) KS methods, i.e., proper density
      functional methods, if the orbital basis set and the auxiliary basis set
      representing the exchange potential are balanced to each other, i.e., if the
      orbital basis is comprehensive enough for a given auxiliary basis. Otherwise xOEP
      methods do not represent EXX KS methods and yield unphysical exchange potentials.
      The question whether a xOEP method properly represents a KS method with an
      exchange potential that is a functional derivative of the exchange energy is
      related to the problem of the definition of local multiplicative operators in
      finite basis representations. Plane wave calculations for bulk silicon illustrate
      the findings of this work.

PMID- 18345875
TI  - Recursive inverse factorization.
AB  - A recursive algorithm for the inverse factorization S(-1)=ZZ(*) of Hermitian
      positive definite matrices S is proposed. The inverse factorization is based on
      iterative refinement [A.M.N. Niklasson, Phys. Rev. B 70, 193102 (2004)] combined
      with a recursive decomposition of S. As the computational kernel is matrix-matrix
      multiplication, the algorithm can be parallelized and the computational effort
      increases linearly with system size for systems with sufficiently sparse
      matrices. Recent advances in network theory are used to find appropriate
      recursive decompositions. We show that optimization of the so-called network
      modularity results in an improved partitioning compared to other approaches. In
      particular, when the recursive inverse factorization is applied to overlap
      matrices of irregularly structured three-dimensional molecules.

PMID- 18345876
TI  - Hartree-Fock exchange computed using the atomic resolution of the identity
      approximation.
AB  - In this work, we apply the atomic resolution of the identity (ARI) fitting
      approximation to the computation of Hartree-Fock exchange. The ARI approximation
      is a local modification of the RI approximation that produces an energy which is
      differentiable with respect to nuclear motion, unlike other local applications of
      RI. We justify empirically the use of locality and present timing comparisons of
      ARI, RI, and exact computation for one-, two-, and three-dimensional carbon
      systems. ARI is found to reduce significantly the cost of RI for large systems,
      while retaining accuracy.

PMID- 18345877
TI  - Application of geometric algebra for the description of polymer conformations.
AB  - In this paper a Clifford algebra-based method is applied to calculate polymer
      chain conformations. The approach enables the calculation of the position of an
      atom in space with the knowledge of the bond length (l), valence angle (theta),
      and rotation angle (phi) of each of the preceding bonds in the chain. Hence, the
      set of geometrical parameters {l(i),theta(i),phi(i)} yields all the position
      coordinates p(i) of the main chain atoms. Moreover, the method allows the
      calculation of side chain conformations and the computation of rotations of chain
      segments. With these features it is, in principle, possible to generate
      conformations of any type of chemical structure. This method is proposed as an
      alternative for the classical approach by matrix algebra. It is more
      straightforward and its final symbolic representation considerably simpler than
      that of matrix algebra. Approaches for realistic modeling by means of
      incorporation of energetic considerations can be combined with it. This article,
      however, is entirely focused at showing the suitable mathematical framework on
      which further developments and applications can be built.

PMID- 18345878
TI  - Multireference Brillouin-Wigner coupled cluster method with singles, doubles, and
      triples: efficient implementation and comparison with approximate approaches.
AB  - We have developed an efficient implementation of the multireference Brillouin
      Wigner coupled cluster method with full iterative treatment of connected singles,
      doubles, and triples. Its computational costs are too high for applications to
      larger molecules; however, it can be used as a useful tool for benchmarking
      approximate methods. Performance of the method has been tested on the ground and
      low-lying excited states of the oxygen molecule and on the singlet-triplet gap in
      methylene; the results are in good agreement with experimental data.

PMID- 18345879
TI  - Analytical solution for optimal squeezing of wave packet of a trapped quantum
      particle.
AB  - Optimal control problem with a goal to squeeze wave packet of a trapped quantum
      particle is considered and solved analytically using adiabatic approximation. The
      analytical solution that drives the particle into a highly localized final state
      is presented for a case of an infinite well trapping potential. The presented
      solution may be applied to increase the resolution of atom lithography.

PMID- 18345880
TI  - The Kohn-Sham kinetic energy density as indicator of the electron localization:
      atomic shell structure.
AB  - In this report, it is shown that the Kohn-Sham (KS) kinetic energy density (KED)
      contains the average local electrostatic potential (ALEP) and the average local
      ionization energy (ALIE); the shell structure in atomic systems is presented as
      one application of the KS-KED. By writing the KS-KED from the KS equations, this
      quantity was divided in three contributions: orbital, Coulomb, and exchange
      correlation. By studying several closed and open shell atoms, the shell structure
      was established by the maxima presented by the Coulomb contribution and the
      minima in the orbital contribution of the KS-KED. The exchange-correlation
      contribution to the KS-KED does not show maxima or minima, but this quantity
      shows bumps where the division between shells is expected. The results obtained
      in this work were compared with other shell structure indicators such as the
      electron localization function, the ALEP, the ALIE, and the radial distribution
      function. The most important result in this work is related to the fact that even
      when the ALEP and the ALIE functions were built with different arguments to each
      other, they are contained in the KS-KED. In this way, the KS-KED shows its
      importance to reveal the electron localization in atomic systems.

PMID- 18345881
TI  - Adaptive minimum action method for the study of rare events.
AB  - An adaptive minimum action method is proposed for computing the most probable
      transition paths between stable equilibria in metastable systems that do not
      necessarily have an underlying energy function, by minimizing the action
      functional associated with such transition paths. This new algorithm uses the
      moving mesh strategy to adaptively adjust the grid points over the time interval
      of transition. Numerical examples are presented to demonstrate the efficiency of
      the adaptive minimum action method.

PMID- 18345882
TI  - Zero kinetic energy photoelectron spectroscopy of tetracene using laser
      desorption for vaporization.
AB  - Far infrared (FIR) spectroscopy of polycyclic aromatic hydrocarbons is of
      particular interest to astrophysics since vibrational modes in this range are
      representative of the molecular size and shape. This information is hence
      important for identification of chemical compositions and for modeling of the IR
      spectrum observed in the outer space. In this work, we report neutral and cation
      FIR spectroscopy of tetracene vaporized from a laser desorption source. Results
      from two-color resonantly enhanced multiphoton ionization and two-color zero
      kinetic energy photoelectron spectroscopy will be presented. Several skeletal
      vibrational modes of the first electronically excited state of the neutral
      species and those of the cation are assigned, with the aid of ab initio and
      density functional calculations. The adiabatic ionization potential is determined
      to be 55 918 +/- 7 cm(-1). Interestingly, all observed vibrational modes can be
      rationalized based on a simple Huckle calculation, i.e., by observing the
      addition or elimination of nodal planes due to electronic excitation and/or
      ionization. Limited by the Franck-Condon principle and the rigidity of the
      molecular frame of tetracene, only IR forbidden modes are observed in this work.

PMID- 18345883
TI  - Electronic spectrum of TaO and its hyperfine structure.
AB  - The B (2)Phi(5/2)-X(1) (2)Delta(3/2)(0,0) band at 778 nm and the C (2)Delta(3/2)
      X(1) (2)Delta(3/2)(0,0) band at 737 nm of tantalum oxide (TaO) were recorded by
      laser excitation spectroscopy using a hollow cathode sputtering source to
      generate the molecules. The hyperfine structure arising from the (181)Ta (I=72)
      nucleus was measured at sub-Doppler resolution using the technique of
      intermodulated fluorescence spectroscopy. The hyperfine structure was assigned
      and fitted in order to derive accurate values for the magnetic dipole and
      electric quadrupole interactions. The magnetic hyperfine constant for the ground
      electronic state was also calculated using the density functional theory as
      h(3/2)=625 MHz, in good agreement with the experimental value of 647+/-10 MHz.
      This result suggests that the X (2)Delta ground state of TaO is well described by
      a pure deltasigma(2) electronic configuration, where the unpaired electron is
      located in a Ta 5ddelta orbital.

PMID- 18345884
TI  - Electron attachment to Ni(PF(3))(4) and Pt(PF(3))(4).
AB  - An experimental study has been made of thermal electron attachment to the
      transition-metal trifluorophosphine complexes Ni(PF(3))(4) and Pt(PF(3))(4) using
      a flowing-afterglow Langmuir-probe apparatus. Both complexes are efficient at
      electron attachment, although the rate constants are somewhat less than
      collisional. The rate constant for electron attachment to Ni(PF(3))(4) is 1.9 x
      10(-7) cm(3) s(-1) at room temperature, about a factor of 2 less than
      collisional. The activation energy is 39+/-5 meV for the attachment reaction. The
      rate constant for electron attachment to Pt(PF(3))(4) is 5.4 x 10(-8) cm(3) s(-1)
      at room temperature, and the activation energy is 84+/-8 meV. For both complexes,
      a PF(3) ligand is lost on electron attachment, and only the M(PF(3))(3)(-) ion is
      observed in the negative-ion mass spectrum. Density functional calculations were
      carried out on Ni(PF(3))(4) and various fragments in order to describe the
      thermochemistry of the attachment reaction.

PMID- 18345885
TI  - Fragmentation of metastable SF(6)(-*) ions with microsecond lifetimes in
      competition with autodetachment.
AB  - Fragmentation of metastable SF(6)(-*) ions formed in low energy electron
      attachment to SF(6) has been investigated. The dissociation reaction SF(6)(-*)-
      >SF(5) (-)+F has been observed approximately 1.5-3.4 micros and approximately 17
      32 micros after electron attachment in a time-of-flight and a double focusing two
      sector field mass spectrometer, respectively. Metastable dissociation is observed
      with maximum intensity at approximately 0.3 eV between the SF(6)(-*) peak at zero
      and the SF(5)(-) peak at approximately 0.4 eV. The kinetic energy released in
      dissociation is low, with a most probable value of 18 meV. The lifetime of SF(6)(
      *) decreases as the electron energy increases, but it is not possible to fit this
      decrease with statistical Rice-Ramsperger-Kassel/quasiequilibrium theory.
      Metastable dissociation of SF(6)(-*) appears to compete with autodetachment of
      the electron at all electron energies.

PMID- 18345886
TI  - Excited states of the water molecule: analysis of the valence and Rydberg
      character.
AB  - The excited states of the water molecule have been analyzed by using the extended
      quantum-chemical multistate CASPT2 method, namely, MS-CASPT2, in conjunction with
      large one-electron basis sets of atomic natural orbital type. The study includes
      13 singlet and triplet excited states, both valence and 3s-, 3p-, and 3d-members
      of the Rydberg series converging to the lowest ionization potential and the 3s-
      and 3p-Rydberg members converging to the second low-lying state of the cation, 1
      (2)A(1). The research has been focused on the analysis of the valence or Rydberg
      character of the low-lying states. The computation of the 1 (1)B(1) state of
      water at different geometries indicates that it has a predominant 3s-Rydberg
      character at the equilibrium geometry of the molecule but it becomes
      progressively a valence state described mainly by the one-electron 1b(1)-->4a(1)
      promotion, as expected from a textbook of general chemistry, upon elongation of
      the O-H bonds. The described valence-Rydberg mixing is established to be
      originated by a molecular orbital (MO) Rydbergization process, as suggested
      earlier by R. S. Mulliken [Acc. Chem. Res. 9, 7 (1976)]. The same phenomenon
      occurs also for the 1 (1)A(2) state whereas a more complex behavior has been
      determined for the 2 (1)A(1) state, where both MO Rydbergization and
      configurational mixing take place. Similar conclusions have been obtained for the
      triplet states of the molecule.

PMID- 18345887
TI  - Infrared-vacuum ultraviolet-pulsed field ionization-photoelectron study of
      CH(3)I(+) using a high-resolution infrared laser.
AB  - By using a high-resolution single mode infrared-optical parametric oscillator
      laser to prepare CH(3)I in single (J,K) rotational levels of the nu(1) (symmetric
      C-H stretching) =1 vibrational state, we have obtained rovibrationally resolved
      infrared-vacuum ultraviolet-pulsed field ionization-photoelectron (IR-VUV-PFI-PE)
      spectra of the CH(3)I(+)(X(2)E(32);nu(1)(+)=1;J(+),P(+)) band, where (J,K) and
      (J(+),P(+)) represent the respective rotational quantum numbers of CH(3)I and
      CH(3)I(+). The IR-VUV-PFI-PE spectra observed for K=0 and 1 are found to have
      nearly identical structures. The IR-VUV-PFI-PE spectra for (J,K)=(5,0) and (7, 0)
      are also consistent with the previous J-selected IR-VUV-PFI-PE measurements. The
      analysis of these spectra indicates that the photoionization cross section of
      CH(3)I depends strongly on DeltaJ(+)=J(+)-J: but not on J and K. This observation
      lends strong support for the major assumption adopted for the semiempirical
      simulation scheme, which has been used for the simulation of the origin bands
      observed in VUV-PFI-PE study of polyatomic molecules. Using the state-to-state
      photoionization cross sections determined in this IR-VUV study, we have obtained
      excellent simulation of the VUV-PFI-PE origin band of CH(3)I(+)(X (2)E(32)),
      yielding more precise IE(CH(3)I)=76 930.7+/-0.5 cm(-1) and nu(1) (+)=2937.8+/-0.2
      cm(-1).

PMID- 18345888
TI  - Dynamics at conical intersections: the influence of O-H stretching vibrations on
      the photodissociation of phenol.
AB  - Comparing the recoil energy distributions of the fragments from one-photon
      dissociation of phenol-d(5) with those from vibrationally mediated
      photodissociation shows that initial vibrational excitation strongly influences
      the disposal of energy into relative translation. The measurements use velocity
      map ion imaging to detect the H-atom fragments and determine the distribution of
      recoil energies. Dissociation of phenol-d(5) molecules with an initially excited
      O-H stretching vibration produces significantly more fragments with low recoil
      energies than does one-photon dissociation at the same total energy. The
      difference appears to come from the increased probability of adiabatic
      dissociation in which a vibrationally excited molecule passes around the conical
      intersection between the dissociative state and the ground state to produce
      electronically excited phenoxyl-d(5) radicals. The additional energy deposited in
      electronic excitation of the radical reduces the energy available for relative
      translation.

PMID- 18345889
TI  - Experimental and theoretical studies of the CN-Ar van der Waals complex.
AB  - The CN-Ar van der Waals complex has been observed using the B (2)Sigma(+)-X
      (2)Sigma(+) and A (2)Pi-X (2)Sigma(+) electronic transitions. The spectra yield a
      dissociation energy of D(0")=102+/-2 cm(-1) and a zero-point rotational constant
      of B(0")=0.067+/-0.005 cm(-1) for CN(X)-Ar. The dissociation energy for CN(A)-Ar
      was found to be D(0')=125+/-2 cm(-1). Transitions to vibrationally excited levels
      of CN(B)-Ar dominated the B-X spectrum, indicative of substantial differences in
      the intermolecular potential energy surfaces (PESs) for the X and B states. Ab
      initio PESs were calculated for the X and B states. These were used to predict
      rovibrational energy levels and van der Waals bond energies (D(0")=115 and
      D(0')=183 cm(-1)). The results for the X state were in reasonably good agreement
      with the experimental data. Spectral simulations based on the ab initio
      potentials yielded qualitative insights concerning the B-X spectrum, but the
      level of agreement was not sufficient to permit vibronic assignment. Electronic
      predissociation was observed for both CN(A)-Ar and CN(B)-Ar. The process leading
      to the production of CN(A,nu=8,9) fragments from the predissociation of
      CN(B,nu=0)-Ar was characterized using time-resolved fluorescence and optical
      optical double resonance measurements.

PMID- 18345890
TI  - Solvation of O(2)(-) and O(4)(-) by p-difluorobenzene and p-xylene studied by
      photoelectron spectroscopy.
AB  - Anion photoelectron spectra of the O(2)(-) . arene and O(4)(-) . arene complexes
      with p-xylene and p-difluorobenzene are presented and analyzed with the aid of
      calculations on the anions and corresponding neutrals. Relative to the adiabatic
      electron affinity of O(2), the O(2)(-) . arene spectra are blueshifted by 0.75-1
      eV. Solvation energy alone does not account for this shift, and it is proposed
      that a repulsive portion of the neutral potential energy surface is accessed in
      the detachment, resulting in dissociative photodetachment. O(2)(-) is found to
      interact more strongly with the p-difluorobenzene than the p-xylene. The binding
      motif involves the O(2)(-) in plane with the arene, interacting via electron
      donation along nearby C-H bonds. A peak found at 4.36(2) eV in the photoelectron
      spectrum of O(2)(-) . p-difluorobenzene (p-DFB) is tentatively attributed to the
      charge transfer state, O(2)(-) . p-DFB(+). Spectra of O(4)(-) . arene complexes
      show less blueshift in electron binding energy relative to the spectrum of bare
      O(4)(-), which itself undergoes dissociative photodetachment. The striking
      similarity between the profiles of the O(4)(-) . arene complexes with the O(4)(-)
      spectrum suggests that the O(4)(-) molecule remains intact upon complex
      formation, and delocalization of the charge across the O(4)(-) molecule results
      in similar structures for the anion and neutral complexes.

PMID- 18345891
TI  - Hydrogen detachment of the hydrated hydrohalogen acids upon attaching an excess
      electron.
AB  - High level ab initio calculations are employed to investigate the excess electron
      attachment to the hydrated hydrohalogen acids. The excess electron leads to the
      dissociation of hydrogen halide acids, which results in the release of a hydrogen
      radical. Neutral HCl, HBr, and HI are dissociated by tetrahydration. Upon binding
      an excess electron, these hydrated hydrohalogen acids show that (i) the H-X bond
      strength weakens with redshifted H-X stretching frequencies, (ii) HX can have a
      bound-electron state, a dissociated structure, or a zwitter-ionic structure, and
      (iii) HClHBr is dissociated by tri/mono-hydration, while HI is dissociated even
      without hydration. This dissociation is in contrast to the case of electron
      attachment to hydrated hydrogen fluoric acids for which HF is not dissociated by
      more than ten water molecules.

PMID- 18345892
TI  - Adiabatic intramolecular movements for water systems.
AB  - An effective treatment of the intramolecular degrees of freedom is presented for
      water, where these modes are decoupled from the intermolecular ones,
      "adiabatically" allowing these coordinates to be positioned at their local
      minimum of the potential energy surface. We perform ab initio Monte Carlo
      simulations with the configurational energies obtained via density functional
      theory. We study a water dimer as a prototype system, and even in this simple
      case the intramolecular relaxations are very important to properly describe
      properties such as the dipole moment. We show that rigid simulations do not
      correctly sample the phase space, resulting in an average dipole moment smaller
      than the one obtained with the adiabatic model, which is closer to the
      experimental result.

PMID- 18345893
TI  - Phosphorescence excitation spectrum of the T(1)(n,pi*)<--S(0) transition of 4H
      pyran-4-one.
AB  - The phosphorescence excitation (PE) spectrum of 4H-pyran-4-one (4PN) vapor at 40
      50 degrees C was recorded near 366 nm. The most intense vibronic feature in this
      region of the spectrum is the T(1)(n,pi*)<--S(0) origin band. The value of nu(0)
      for the 0(0)(0) transition was determined to be 27 291.5 cm(-1) by comparing the
      observed spectrum to a simulation in the T(1)<--S(0) origin-band region. Attached
      to the origin band in the PE spectrum are several Deltav=0 sequence bands
      involving low-frequency ring modes. From the positions of these bands, together
      with the known ground-state combination differences, fundamental frequencies for
      nu(18') (ring bending), nu(13') (ring twisting), and nu(10') (in-plane ring
      deformation) in the T(1)(n,pi*) excited state were determined to be 126, 269, and
      288 cm(-1), respectively. These values represent drops of 15%, 32%, and 43%,
      compared to the respective fundamental frequencies in the S(0) state. The changes
      in these ring frequencies indicate that the effects of T(1)(n,pi*)<--S(0)
      excitation extend beyond the nominal carbonyl chromophore and involve the
      conjugated ring atoms as well. The delocalization may be more extensive for
      T(1)(n,pi*) than for S(1)(n,pi*) excitation.

PMID- 18345894
TI  - Generation and orientation of organoxenon molecule H-Xe-CCH in the gas phase.
AB  - We report on the first observation of the organoxenon HXeCCH molecule in the gas
      phase. This molecule has been prepared in a molecular beam experiment by 193 nm
      photolysis of an acetylene molecule on Xe(n) clusters (n approximately 390).
      Subsequently the molecule has been oriented via the pseudo-first-order Stark
      effect in a strong electric field of the polarized laser light combined with the
      weak electrostatic field in the extraction region of a time-of-flight
      spectrometer. The experimental evidence for the oriented molecule has been
      provided by measurements of its photodissociation. For comparison, photolysis of
      C(2)H(2) on Ar(n) clusters (n approximately 280) has been measured. Here the
      analogous rare gas molecule HArCCH could not be generated. The interpretation of
      our experimental findings has been supported by ab initio calculations. In
      addition, the experiment together with the calculations reveals information on
      the photochemistry of the HXeCCH molecule. The 193 nm radiation excites the
      molecule predominantly into the 2 (1)Sigma(+) state, which cannot dissociate the
      Xe-H bond directly, but the system evolves along the Xe-C coordinate to a conical
      intersection of a slightly nonlinear configuration with the dissociative 1 (1)Pi
      state, which then dissociates the Xe-H bond.

PMID- 18345895
TI  - Exploring the correlation between network structure and electron binding energy
      in the (H(2)O)(7)(-) cluster through isomer-photoselected vibrational
      predissociation spectroscopy and ab initio calculations: addressing complexity
      beyond types I-III.
AB  - We report a combined photoelectron and vibrational spectroscopy study of the
      (H(2)O)(7)(-) cluster anions in order to correlate structural changes with the
      observed differences in electron binding energies of the various isomers.
      Photoelectron spectra of the (H(2)O)(7)(-) . Ar(m) clusters are obtained over the
      range of m=0-10. These spectra reveal the formation of a new isomer (I') for m>5,
      the electron binding energy of which is about 0.15 eV higher than that of the
      type I form previously reported to be the highest binding energy species [Coe et
      al., J. Chem. Phys. 92, 3980 (1990)]. Isomer-selective vibrational
      predissociation spectra are obtained using both the Ar dependence of the isomer
      distribution and photochemical depopulation of the more weakly (electron) binding
      isomers. The likely structures of the isomers at play are identified with the aid
      of electronic structure calculations, and the electron binding energies, as well
      as harmonic vibrational spectra, are calculated for 28 low-lying forms for
      comparison with the experimental results. The HOH bending spectrum of the low
      binding type II form is dominated by a band that is moderately redshifted
      relative to the bending origin of the bare water molecule. Calculations trace
      this feature primarily to the bending vibration localized on a water molecule in
      which a dangling H atom points toward the electron cloud. Both higher binding
      forms (I and I') display the characteristic patterns in the bending and OH
      stretching regions signaling electron attachment primarily to a water molecule in
      an AA binding site, a persistent motif found in non-isomer-selective spectra of
      the clusters up to (H(2)O)(50)(-).

PMID- 18345896
TI  - Selective photodissociation in diatomic molecules by dynamical Stark-shift
      control.
AB  - Selective population transfer in electronic states of dissociative molecular
      systems is illustrated by adopting a control scheme based on Stark-chirped rapid
      adiabatic passage (SCRAP). In contrast to the discrete N-level system, dynamical
      Stark shift is induced in a more complex manner in the molecular electronic
      states. Wavepacket dynamics on the light-induced potentials, which are determined
      by the detuning of the pump pulse, can be controlled by additional Stark pulse in
      the SCRAP scheme. Complete population transfer can be achieved by either lowering
      the energy barrier along the adiabatic passage or placing the initial wavepacket
      on a well-defined dressed state suitable for the control. The determination of
      the pulse sequence is sufficient for controlling population transfer to the
      target state.

PMID- 18345897
TI  - Structures and relative stability of medium- and large-sized silicon clusters.
      VI. Fullerene cage motifs for low-lying clusters Si(39), Si(40), Si(50), Si(60),
      Si(70), and Si(80).
AB  - We performed a constrained search, combined with density-functional theory
      optimization, of low-energy geometric structures of silicon clusters Si(39),
      Si(40), Si(50), Si(60), Si(70), and Si(80). We used fullerene cages as structural
      motifs to construct initial configurations of endohedral fullerene structures.
      For Si(39), we examined six endohedral fullerene structures using all six homolog
      C(34) fullerene isomers as cage motifs. We found that the Si(39) constructed
      based on the C(34)(C(s):2) cage motif results in a new leading candidate for the
      lowest-energy structure whose energy is appreciably lower than that of the
      previously reported leading candidate obtained based on unbiased searches
      (combined with tight-binding optimization). The C(34)(C(s):2) cage motif also
      leads to a new candidate for the lowest-energy structure of Si(40) whose energy
      is notably lower than that of the previously reported leading candidate with
      outer cage homolog to the C(34)(C(1):1). Low-lying structures of larger silicon
      clusters Si(50) and Si(60) are also obtained on the basis of preconstructed
      endohedral fullerene structures. For Si(50), Si(60), and Si(80), the obtained low
      energy structures are all notably lower in energy than the lowest-energy silicon
      structures obtained based on an unbiased search with the empirical Stillinger
      Weber potential of silicon. Additionally, we found that the binding energy per
      atom (or cohesive energy) increases typically >10 meV with addition of every ten
      Si atoms. This result may be used as an empirical criterion (or the minimal
      requirement) to identify low-lying silicon clusters with size larger than Si(50).

PMID- 18345898
TI  - Barrierless reactions between two closed-shell molecules. I. Dynamics of
      F(2)+CH(3)SCH(3) reaction.
AB  - A detailed experimental and theoretical investigation of the first-reported
      barrierless reaction between two closed-shell molecules [J. Chem. Phys. 127,
      101101 (2007)] is presented. The translational energy and angular distributions
      of two product channels, HF+CH(2)SFCH(3) and F+CH(3)SFCH(3), determined at
      several collision energies, have been analyzed to reveal the dynamics of the
      studied reaction. Detailed analysis of the experimental and computational results
      supports the proposed reaction mechanism involving a short-lived F-F-S(CH(3))(2)
      intermediate, which can be formed without any activation energy. Other possible
      reaction mechanisms have been discriminated. The decay of the intermediate and
      competition between the two product channels have been discussed.

PMID- 18345899
TI  - Vibrational ground state properties of H(5)(+) and its isotopomers from diffusion
      Monte Carlo calculations.
AB  - Diffusion Monte Carlo computations, with and without importance sampling, of the
      zero-point properties of H(5)(+) and its isotopomers using a recent high accuracy
      global potential energy surface are presented. The global minimum of the
      potential possesses C(2v) symmetry, but the calculations predict a D(2d) geometry
      for zero-point averaged structure of H(5)(+) with one H atom "in the middle"
      between two HH diatoms. The predicted zero-point geometries of the deuterated
      forms have H in the middle preferred over D in the middle and for a nonsymmetric
      arrangement of D atoms the preferred arrangement is one which maximizes the
      number of D as the triatomic ion. We speculate on the consequences of these
      preferences in scattering of H(2)+H(3)(+) and isotopomers at low energies, such
      as those in the interstellar medium.

PMID- 18345900
TI  - Efficient prediction of thermodynamic properties of quadrupolar fluids from
      simulation of a coarse-grained model: the case of carbon dioxide.
AB  - Monte Carlo simulations are presented for a coarse-grained model of real
      quadrupolar fluids. Molecules are represented by particles interacting with
      Lennard-Jones forces plus the thermally averaged quadrupole-quadrupole
      interaction. The properties discussed include the vapor-liquid coexistence curve,
      the vapor pressure along coexistence, and the surface tension. The full isotherms
      are also accessible over a wide range of temperatures and densities. It is shown
      that the critical parameters (critical temperature, density, and pressure) depend
      almost linearly on a quadrupolar parameter q=Q(*4)T*, where Q* is the reduced
      quadrupole moment of the molecule and T* the reduced temperature. The model can
      be applied to a variety of small quadrupolar molecules. We focus on carbon
      dioxide as a test case, but consider nitrogen and benzene, too. Experimental
      critical temperature, density, and quadrupolar moment are sufficient to fix the
      parameters of the model. The resulting agreement with experiments is excellent
      and marks a significant improvement over approaches which neglect quadrupolar
      effects. The same coarse-grained model was also applied in the framework of
      perturbation theory in the mean spherical approximation. As expected, the latter
      deviates from the Monte Carlo results in the critical region, but is reasonably
      accurate at lower temperatures.

PMID- 18345901
TI  - Bond connectivity measured via relaxation-assisted two-dimensional infrared
      spectroscopy.
AB  - The relaxation-assisted two-dimensional infrared (RA 2DIR) method is a novel
      technique for probing structures of molecules, which relies on vibrational energy
      transport in molecules. In this article we demonstrate the ability of RA 2DIR to
      detect the bond connectivity patterns in molecules using two parameters, a
      characteristic intermode energy transport time (arrival time) and a cross-peak
      amplification coefficient. A correlation of the arrival time with the distance
      between the modes is demonstrated. An 18-fold amplification of the cross-peak
      amplitude for the modes separated by approximately 11 A is shown using RA 2DIR;
      larger cross-peak amplifications are expected for the modes separated by larger
      distances. The RA 2DIR method enhances the applicability of 2DIR spectroscopy by
      making practical the long-range measurements using a variety of structural
      reporters, including weak IR modes. The data presented demonstrate the analytical
      power of RA 2DIR which permits the speedy structural assessments of the bond
      connectivity patterns.

PMID- 18345902
TI  - Structural precursor to freezing: an integral equation study.
AB  - Recent simulation studies have drawn attention to the shoulder which forms in the
      second peak of the radial distribution function of hard spheres at densities
      close to freezing and which is associated with local crystalline ordering in the
      dense fluid. We address this structural precursor to freezing using an
      inhomogeneous integral equation theory capable of describing local packing
      constraints to a high level of accuracy. The addition of a short-range attractive
      interaction leads to a well known broadening of the fluid-solid coexistence
      region as a function of attraction strength. The appearance of a shoulder in our
      calculated radial distribution functions is found to be consistent with the
      broadened coexistence region for a simple model potential, thus demonstrating
      that the shoulder is not exclusively a high density packing effect.

PMID- 18345903
TI  - New contributions to the photophysical model for all-trans-polyenes from ttbP4, a
      nonphotolabile octatetraene.
AB  - All-trans-octatetraene 3,10-di(tert-butyl)-2,2,11,11-tetramethyl-3,5,7,9
      dodecatetraene emits fluorescence in three different regions of the visible
      spectrum. Thus, it produces an extremely weak emission in the gas phase that can
      hardly be detected in the condensed phase; such an emission exhibits a negligible
      Stokes shift with respect to the 1A(g)-->1B(u) absorption transition and can, in
      principle, be assigned to the 1B(u)-->1A(g) emission for the compound. A second,
      structureless fluorescence emission, centered in the region of 525 nm, is
      observed in the gas phase and at somewhat higher wavelengths in the condensed
      phase [viz., 570 nm in 2-methylbutane (2MB) and 550 nm in squalane (SQ)]. While
      detectable, this emission increases significantly, with no change in spectral
      position, as the solution temperature is lowered; also, it is abruptly replaced
      by a new, strongly blueshifted emission at approximately 490 nm in 2MB and 455 mm
      in SQ when the viscosity of the medium exceeds a given level. The fact that the
      two fluorescence emissions considerably depart from the expected behavior for a
      1B(u)-->1A(g) emission in an all-trans-polyene, and that one disappears while the
      other simultaneously appears as the medium becomes more rigid, suggests that the
      two emissions are produced by two different molecular structures and that the
      rigidity of the medium switches their production from the originally excited all
      trans 1B(u) form. The observed spectral behavior is consistent with a recently
      proposed model [J. Catalan, Chem. Phys. 335, 69 (2007)] in which the 1B(u)
      excited state of octatetraene can give two distinct molecular conformers as a
      result of twisting about different C-C single bonds.

PMID- 18345904
TI  - Intermediate motions as studied by solid-state separated local field NMR
      experiments.
AB  - In this report, the application of a class of separated local field NMR
      experiments named dipolar chemical shift correlation (DIPSHIFT) for probing
      motions in the intermediate regime is discussed. Simple analytical procedures
      based on the Anderson-Weiss (AW) approximation are presented. In order to
      establish limits of validity of the AW based formulas, a comparison with spin
      dynamics simulations based on the solution of the stochastic Liouville-von
      Neumann equation is presented. It is shown that at short evolution times (less
      than 30% of the rotor period), the AW based formulas are suitable for fitting the
      DIPSHIFT curves and extracting kinetic parameters even in the case of jumplike
      motions. However, full spin dynamics simulations provide a more reliable
      treatment and extend the frequency range of the molecular motions accessible by
      DIPSHIFT experiments. As an experimental test, molecular jumps of imidazol methyl
      sulfonate and trimethylsulfoxonium iodide, as well as the side-chain motions in
      the photoluminescent polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4
      phenylenevinylene], were characterized. Possible extensions are also discussed.

PMID- 18345905
TI  - Hydrophobic solvation of Gay-Berne particles in modified water models.
AB  - The solvation of large hydrophobic solutes, modeled as repulsive and attractive
      Gay-Berne oblate ellipsoids, is characterized in several modified water liquids
      using the SPC/E model as the reference water fluid. We find that small amounts of
      attraction between the Gay-Berne particle and any model fluid result in wetting
      of the hydrophobic surface. However, significant differences are found among the
      modified and SPC/E water models and the critical distances in which they dewet
      the hydrophobic surfaces of pairs of repulsive Gay-Berne particles. We find that
      the dewetting trends for repulsive Gay-Berne particles in the various model
      liquids correlate directly with their surface tensions, the widths of the
      interfaces they form, and the openness of their network structure. The largest
      critical separations are found in liquids with the smallest surface tensions and
      the broadest interfaces as measured by the Egelstaff-Widom length.

PMID- 18345906
TI  - Three-point frequency fluctuation correlation functions of the OH stretch in
      liquid water.
AB  - Characterizing the dynamics of the OH stretch in isotopically substituted liquid
      water (HOD in D(2)O) in terms of three-point frequency fluctuation correlation
      functions and joint probability densities shows that dynamics during hydrogen
      bond rearrangements occur primarily along a coordinate which is perpendicular to
      the spectroscopic coordinate. Molecular dynamics simulations show that three
      point correlation functions are sensitive to this motion, unlike two-point
      correlation functions, and can select sets of trajectories which linger in the
      area of the transition state. Three-dimensional-infrared correlation spectroscopy
      could potentially measure these dynamics, though motional narrowing significantly
      changes the shape of the resulting spectra.

PMID- 18345907
TI  - Factors influencing deformation stability of binary glasses.
AB  - A possible mechanism of strain accommodation in large deformation of glasses is
      crystallization; deformation stability is a measure of the resistance of glasses
      to crystallization. We study the effect of atomic size ratio and atomic stiffness
      parameter (related to the curvature of the interatomic potential) on deformation
      stability of binary glasses using molecular static simulations. The deformation
      stability of a glass is found to increase with increasing atomic size ratio and
      magnitude of the atomic stiffness, which is proportional to the bulk modulus of
      the pure crystalline system, as well as the ratio of atomic stiffnesses of
      constituent atoms. To understand the role of the above parameters on deformation
      stability, misfit energies of randomly substituted solid solution fcc crystals
      and glasses are compared for various atomic size ratios and atomic stiffness
      values. Unlike in fcc solid solution, the misfit energy of binary glasses is
      found to be insensitive to the atomic size ratio. It is also found that the
      packing fraction of glasses is insensitive to the atomic size ratio, consistent
      with the above result. Beyond a critical atomic size ratio, the misfit energy of
      fcc solid solution exceeds the energy of the glass, thus making the amorphous
      state completely stable to deformation induced crystallization. Our analysis
      shows that critical atomic size ratio decreases with increasing atomic stiffness
      which leads to an increase in the deformation stability of glasses.

PMID- 18345908
TI  - The stability of a salt-free colloidal dispersion.
AB  - The electrical potential for the case of two identical, planar parallel particles
      immersed in a salt-free medium, where the ionic species in the counterions come
      solely from those that dissociated from the surfaces, is evaluated. Analytical
      expressions for the electrical potential, the concentration of counterions, and
      the electrical energy are derived. We show that in a salt-free dispersion, if the
      separation distance between two particles is sufficiently far, the electrical
      repulsive force dominates, that is, the total energy is positive and does not
      have a secondary minimum, which is not the case for a dispersion where both
      coions and counterions are present. Also, the conditions used to calculate the
      critical coagulation concentration in the classic Derjaguin-Landau-Verwey
      Overbeek theory become inappropriate and the Derjaguin approximation is
      inapplicable. We show that if the surface charge density exceeds approximately
      0.04 Cm(2), the stability of a salt-free dispersion remains essentially the same.
      If the surface charge density is sufficiently high, the maximum separation
      distance between two particles below which coagulation occurs is in the ranges of
      [0,1 nm] and [1,7 nm] for the cases where the Hamaker constant is 10(-20) and 10(
      19) J, respectively.

PMID- 18345909
TI  - New topic of supercritical fluids: local activity coefficients of supercritical
      solvent and cosolvent around solute.
AB  - The study of inhomogeneity in supercritical fluids (SCFs) is of great importance.
      In this work, we propose the concept of local activity coefficients in
      supercritical (SC) solutions, which link thermodynamics and inhomogeneity in SC
      systems. The local activity coefficients of CO(2)+acetonitrile+phenol blue and
      CO(2)+acetic acid+phenol blue systems are investigated at 308.15 K in critical
      region and outside critical region. To do this, the local compositions of
      CO(2)+acetonitrile and CO(2)+acetic acid mixed solvents around phenol blue are
      first estimated using UV-visible spectroscopy. Then it is considered that there
      exist bulk phase and local phase around phenol blue in the systems. The activity
      coefficients of CO(2) and the cosolvents (acetonitrile or acetic acid) in bulk
      phase are calculated using Peng-Robinson equation of state. The local activity
      coefficients of CO(2) and the cosolvents are then calculated on the basis of
      thermodynamic principles. It is demonstrated that in the critical region the
      local activity coefficients differ from bulk activity coefficients significantly
      and are sensitive to pressure. This can explain many unusual phenomena in SC
      systems in critical region thermodynamically.

PMID- 18345910
TI  - Phase behavior of density-dependent pair potentials.
AB  - Phase diagram is calculated by a recently proposed third-order thermodynamic
      perturbation theory (TPT) for fluid phase and a recently proposed first-order TPT
      for solid phases; the underlying interparticle potential consists of a hard
      sphere repulsion and a perturbation tail of an attractive inverse power law type
      or Yukawa type whose range varies with bulk densities. It is found that besides
      usual phase transitions associated with density-independent potentials, the
      density dependence of the perturbation tail evokes some additional novel phase
      transitions including isostructural solid-solid transition and liquid-liquid
      transition. Novel triple points are also exhibited which includes stable fluid
      (vapor or liquid)-face-centered cubic(fcc)-fcc and liquid-liquid-fcc, metastable
      liquid-body-centered cubic(bcc)-bcc. It also is found that the phase diagram
      sensitively depends on the density dependence and the concrete mathematical form
      of the underlying potentials. Some of the disclosed novel transitions has been
      observed experimentally in complex fluids and molecular liquids, while others
      still remain to be experimentally verified.

PMID- 18345911
TI  - The dissociation and equation of state of dense fluid oxygen at high pressures
      and high temperatures.
AB  - The dissociation, pressure, and internal energy of dense fluid oxygen at high
      temperatures and densities have been calculated from the free-energy functions
      using the self-consistent fluid variational theory. In this paper, we focused on
      a mixture of oxygen atoms and molecules, and investigated the phenomenon of
      pressure dissociation at finite temperature. The single-shock Hugoniot derived
      from this equation of state agrees well with gas-gun experiments for pressure
      versus density. The equation of state and dissociation degree are predicted in
      the ranges of temperature of 5000-16,000 K and density of 0.1-4.5 g/cm(3). These
      data are formulated in the analytical forms of dissociation degree-density
      temperature and pressure-density-temperature equation of state.

PMID- 18345912
TI  - Local biaxiality in cholesteric liquid crystals from the surface interaction
      model.
AB  - The feature of local biaxiality of the orientational order in twisted nematics
      and cholesteric liquid-crystalline phases is faced by modeling the mean field
      orientational potential on the basis of the surface interaction model [A.
      Ferrarini, G. J. Moro, P. L. Nordio, and G. R. Luckhurst, Mol. Phys. 77, 1
      (1992)]. Here we present a tool for the complete parameterization of the
      potential for general molecular structures and recover the long-pitch
      approximation usually invoked to model the molecular order in these phases. The
      method is applied to archetype molecular geometries (an ellipsoidal object, a
      conical object, a lath-shaped molecule, and the shape's enantiomers of a
      propellerlike molecule) in order to evaluate the dependence of the second-rank
      orientational order parameters on the pitch of the phase. Special emphasis is
      given to the so-called biaxiality parameter B [Z. Yaniv, N. A. P. Vaz, G.
      Chidichimo, and J. W. Doane, Phys. Rev. Lett. 47, 46 (1981)], which can be
      experimentally determined by the analysis of time-averaged (2)H-NMR spectra of
      deuterated probes dissolved in the twisted phase. The model calculations show how
      probes with different geometries are sensitive to the local biaxiality.

PMID- 18345913
TI  - The effects of electronic structure and charged state on thermodynamic
      properties: an ab initio molecular dynamics investigations on neutral and charged
      clusters of Na(39), Na(40), and Na(41).
AB  - In this paper we explore the effects of the electronic structure, the charge
      state, and the nature of energy distribution of isomers on the thermodynamic
      properties of sodium clusters. The focus of the work is to isolate the effects of
      these ingredients on thermodynamic behavior by choosing specific clusters. Toward
      this end we investigate Na(39) (-), Na(40), and Na(41) (+), which are the
      electronic closed shell systems which differ in number of atoms and charge state.
      We also examine Na(39), Na(39) (+), Na(40) (+), and Na(41) clusters having
      different charges of these clusters. Our density functional molecular dynamics
      simulations show that all electronic shell-closing clusters have similar melting
      temperature of approximately 310 K. Remarkably, it is observed that an addition
      of even one electron to Na(39) increases the melting temperature by about 40 K
      and makes the specific heat curve sharper. All the cationic clusters show
      broadened specific heat curves.

PMID- 18345914
TI  - The adsorption and desorption of ethanol ices from a model grain surface.
AB  - Reflection absorption infrared spectroscopy (RAIRS) and temperature programed
      desorption (TPD) have been used to probe the adsorption and desorption of ethanol
      on highly ordered pyrolytic graphite (HOPG) at 98 K. RAIR spectra for ethanol
      show that it forms physisorbed multilayers on the surface at 98 K. Annealing
      multilayer ethanol ices (exposures >50 L) beyond 120 K gives rise to a change in
      morphology before crystallization within the ice occurs. TPD shows that ethanol
      adsorbs and desorbs molecularly on the HOPG surface and shows four different
      species in desorption. At low coverage, desorption of monolayer ethanol is
      observed and is described by first-order kinetics. With increasing coverage, a
      second TPD peak is observed at a lower temperature, which is assigned to an
      ethanol bilayer. When the coverage is further increased, a second multilayer,
      less strongly bound to the underlying ethanol ice film, is observed. This peak
      dominates the TPD spectra with increasing coverage and is characterized by
      fractional-order kinetics and a desorption energy of 56.3+/-1.7 kJ mol(-1). At
      exposures exceeding 50 L, formation of crystalline ethanol is also observed as a
      high temperature shoulder on the TPD spectrum at 160 K.

PMID- 18345915
TI  - Nonadiabaticity in the iron bcc to hcp phase transformation.
AB  - Iron is known to undergo a pressure-induced phase transition from the
      ferromagnetic (FM) body-centered-cubic (bcc) alpha-phase to the nonmagnetic (NM)
      hexagonal-close-packed (hcp) epsilon-phase, with a large observed pressure
      hysteresis whose origin is still a matter of debate. Long ago, Burgers [Physica
      (Amsterdam) 1, 561 (1934)] proposed an adiabatic pathway for bcc to hcp
      transitions involving crystal shear followed by atom shuffles. However, a quantum
      mechanics search in six-dimensional stress-strain space reveals a much lower
      energy path, where the crystal smoothly shears along the entire path while the
      atoms shuffle only near the transition state (TS). The energy profile for this
      phase transition path exhibits a cusp at the TS and closely follows bcc and hcp
      diabatic energy wells. Both the cusp and the overlap with diabatic energy
      surfaces are hallmarks of nonadiabaticity, analogous to, e.g., electron transfer
      (ET) reactions in liquids. Fluctuations in the positions of FM bcc iron atoms
      near the TS induce magnetic quenching (akin to solvent fluctuations inducing ET),
      which then promotes NM hcp iron formation (akin to solvent reorganization after
      ET). We propose that the nonadiabatic nature of this transition at the atomic
      scale may contribute to the observed pressure hysteresis.

PMID- 18345916
TI  - NO(2) dissociation on Ag(111) revisited by theory.
AB  - NO(2) dissociation on Ag(111) is investigated with first-principles calculations.
      For single NO(2) molecules, a high adsorption potential energy is found to
      prohibit dissociation. This result is surprising as experiments indicate
      dissociation at low temperatures. Neither entropy effects nor irregularities in
      the potential energy surface can remedy the discrepancy. Instead it is proposed
      that collective Eley-Rideal type of reaction mechanisms can drive the
      dissociation.

PMID- 18345917
TI  - The interfacial properties of MgCl(2) thin films grown on Si(111)7 x 7.
AB  - Photoelectron spectroscopy with synchrotron radiation and low energy electron
      diffraction (LEED) were used in order to study the MgCl(2)Si(111) system. At
      submonolayer coverage of MgCl(2), a new LEED pattern was observed corresponding
      to a (sqr rt 3 x sqr rt 3)R30 degrees overlayer superimposed on the underlying
      reconstructed Si(111)7 x 7. The surface species at this stage are mainly
      molecular MgCl(2) and MgCl(x) (x<2) or MgO(x)Cl(y) attached to the Si substrate
      through Cl bridges coexisting with monodentate SiCl. The interfacial interaction
      becomes more pronounced when the submonolayer coverage is obtained by annealing
      thicker MgCl(2) layers, whereby desorption of molecular MgCl(2) is observed
      leaving on the nonreconstructed silicon surface an approximately 0.2 ML thick
      MgCl(x) layer which again forms the (sqr rt 3 x sqr rt 3 )R30 degrees
      superstructure.

PMID- 18345918
TI  - Density functional theory studies of inorganic metallocene multidecker
      V(n)(P(6))(n+1) (n=1-4) sandwich clusters.
AB  - Motivated by the synthesis of the first entirely inorganic metallocene sandwich
      ion [eta(5)-Ti-(P(5))(2)](2-) [E. Urnezius et al. Science 295, 832 (2002)], we
      have designed a new inorganic metallocene sandwich [eta(6)-V-(P(6))(2)] and
      multidecker sandwich clusters up to V(4)(P(6))(5) by employing an all electron
      gradient-corrected density functional theory. The binding energies of the
      V(n)(P(6))(n+1) complexes increase rapidly from half sandwich to the smallest
      full sandwich and become gradually afterwards. The highest occupied and lowest
      unoccupied molecular orbital gap and the vertical ionization energy decrease with
      increasing cluster size. The V(n)(P(6))(n+1) clusters are nonferromagnetic and
      prefer the lowest available spin states. The smallest sandwich cluster,
      V(P(6))(2), has the high stability and might serve as a building block for one
      dimensional inorganic polymers with high stabilities.

PMID- 18345919
TI  - Nematic ordering and defects on the surface of a sphere: a Monte Carlo simulation
      study.
AB  - We examine the ordering of hard rods on the surface of a sphere using computer
      simulations. As predicted by previous theories of thin nematic shells we observe
      four s = + 1/2 defects. However, the predicted tetrahedral symmetry for the
      defects and the "baseball" director configuration is not observed. Instead the
      four defects are located, on average, on a great circle which splits the sphere
      into two hemispheres, each of which has a splay dominated director configuration.
      We argue that this result occurs as the bend elastic constant for hard rods is
      much larger than the splay elastic constant.

PMID- 18345920
TI  - An investigation of the sodium patterning in Na(x)CoO(2) (0.5 < or = x < or = 1)
      by density functional theory methods.
AB  - Extensive experimental work has been carried out to characterize the stable Na
      vacancy ordering patterns at various compositions of layered Na(x)CoO(2).
      However, contradictions and debates prevail in the literature, particularly at
      high Na concentrations x>0.5. Understanding of the exotic electronic properties
      in this system requires a thorough understanding of the Na-vacancy structural
      orderings. Using density functional theory in the generalized gradient
      approximation (GGA), combined with a cluster expansion structure prediction
      algorithm we have found an intricate set of Na-vacancy ordered ground states in
      Na(x)CoO(2) (0.5< or =x< or =1). We demonstrate a newly predicted ordering
      pattern between 0.67< or =x< or =0.71. By comparing the first principles
      electronic structure methods within the GGA and GGA+U (Hubbard U correction)
      approximations, we demonstrate that at certain Na concentration the stable
      ordering is affected by charge localization on the Co layer through coupling
      between the Na and Co lattices.

PMID- 18345921
TI  - Molecular dynamics of immiscible fluids in chemically patterned nanochannels.
AB  - Molecular dynamics simulations of chain molecules are used to elucidate physical
      phenomena involved in flows of dense immiscible fluids in nanochannels. We first
      consider a force driven flow in which the channel walls are homogeneous and
      wetting to one fluid and nonwetting to the other fluid. The coating of the walls
      by the wetting fluid provides a fluctuating surface that confines the flow of the
      nonwetting fluid. The resulting dissipation yields stationary Poiseuille-like
      flows in contrast to the accelerating nature of flow in the absence of the
      coating. We then consider walls consisting of patches whose wetting preferences
      to a fluid alternate along the walls. In the resulting flow, the immiscible
      components exhibit periodic structures in their velocity fields such that the
      crests are located at the wettability steps in contrast to the behavior of a
      single fluid for which the crest occurs in the wetting region. We demonstrate
      that for a single fluid, the modulated velocity field scales with the size of the
      chain molecules.

PMID- 18345922
TI  - Segmental versus chain dynamics of linear polymers.
AB  - Segmental dynamics of relatively short linear polymers are discussed in terms of
      two distinct contributions, one related to the local segmental motion (alpha
      relaxation) and the other to polymer-specific effects that reflect Brownian
      dynamics of the polymer under chain connectivity constraints (Rouse relaxation
      modes). These two aspects of polymer dynamics are reflected, though differently,
      in relaxation spectra of different experimental techniques. Two contrasting cases
      of the (collective) dipolar response (dielectric techniques) versus the
      individual segmental response (e.g., NMR spin-lattice relaxation spectroscopy)
      are considered. The second-rank orientational correlation function of an
      elementary (Kuhn) segment, directly related to NMR observables, is derived in
      terms of Rouse normal modes. The effect of alpha dynamics is estimated under the
      assumption of a separation of time scales which, as it is argued, is a necessary
      precondition of the Rouse approach. The relative magnitude of the polymer-related
      dynamics is expressed through the number of elementary Rouse units in the chain
      and the number of Kuhn segments in a Rouse unit. The results are discussed in the
      context of recent literature.

PMID- 18345923
TI  - Theoretical study of the three-phase contact line and its tension in adsorbed
      colloid-polymer mixtures.
AB  - We perform a theoretical study of the three-phase contact line and the line
      tension in an adsorbed colloid-polymer mixture near a first-order wetting
      transition, employing an interface displacement model. We use a simple free
      energy functional to describe a colloid-polymer mixture near a hard wall. The
      bulk phase behavior and the substrate-adsorbate interaction are modeled by the
      free-volume theory for ideal polymers. The large size of the colloidal particles
      and the suppression of the van der Waals interaction by optical matching of
      colloid and solvent justify the planar hard wall model for the substrate.
      Following the Fisher-Jin scheme, we derive from the free-energy functional an
      interface potential V(l) for these mixtures. For a particle diameter of 10-100
      nm, the calculations indicate a line tension tau approximately 10(-12)-10(-13) N
      at room temperature. In view of the ultralow interfacial tension in colloid
      polymer mixtures, gamma approximately 10(-7) Nm, this leads to a rather large
      characteristic length scale taugamma in the micrometer range for the three-phase
      contact zone width. In contrast with molecular fluids, this zone could be studied
      directly with optical techniques such as confocal scanning laser microscopy.

PMID- 18345924
TI  - Short-time transport properties in dense suspensions: from neutral to charge
      stabilized colloidal spheres.
AB  - We present a detailed study of short-time dynamic properties in concentrated
      suspensions of charge-stabilized and of neutral colloidal spheres. The particles
      in many of these systems are subject to significant many-body hydrodynamic
      interactions. A recently developed accelerated Stokesian dynamics (ASD)
      simulation method is used to calculate hydrodynamic functions, wave-number
      dependent collective diffusion coefficients, self-diffusion and sedimentation
      coefficients, and high-frequency limiting viscosities. The dynamic properties are
      discussed in dependence on the particle concentration and salt content. Our ASD
      simulation results are compared with existing theoretical predictions, notably
      those of the renormalized density fluctuation expansion method of Beenakker and
      Mazur [Physica A 126, 349 (1984)], and earlier simulation data on hard spheres.
      The range of applicability and the accuracy of various theoretical expressions
      for short-time properties are explored through comparison with the simulation
      data. We analyze, in particular, the validity of generalized Stokes-Einstein
      relations relating short-time diffusion properties to the high-frequency limiting
      viscosity, and we point to the distinctly different behavior of de-ionized charge
      stabilized systems in comparison to hard spheres.

PMID- 18345925
TI  - The electronic structure of the four nucleotide bases in DNA, of their stacks,
      and of their homopolynucleotides in the absence and presence of water.
AB  - Using the ab initio Hartree-Fock crystal orbital method in its linear combination
      of atomic orbital form, the energy band structure of the four homo-DNA-base
      stacks and those of poly(adenilic acid), polythymidine, and polycytidine were
      calculated both in the absence and presence of their surrounding water molecules.
      For these computations Clementi's double zeta basis set was applied. To
      facilitate the interpretation of the results, the calculations were supplemented
      by the calculations of the six narrow bands above the conduction band of
      poly(guanilic acid) with water. Further, the sugar-phosphate chain as well as the
      water structures around poly(adenilic acid) and polythymidine, respectively, were
      computed. Three important features have emerged from these calculations. (1) The
      nonbase-type or water-type bands in the fundamental gap are all close to the
      corresponding conduction bands. (2) The very broad conduction band (1.70 eV) of
      the guanine stack is split off to seven narrow bands in the case of poly(guanilic
      acid) (both without and with water) showing that in the energy range of the
      originally guanine-stack-type conduction band, states belonging to the sugar, to
      PO(4)(-), to Na(+), and to water mix with the guanine-type states. (3) It is
      apparent that at the homopolynucleotides with water in three cases the valence
      bands are very similar (polycytidine, because it has a very narrow valence band,
      does not fall into this category). We have supplemented these calculations by the
      computation of correlation effects on the band structures of the base stacks by
      solving the inverse Dyson equation in its diagonal approximation taken for the
      self-energy the MP2 many body perturbation theory expression. In all cases the
      too large fundamental gap decreased by 2-3 eV. In most cases the widths of the
      valence and conduction bands, respectively, decreased (but not in all cases).
      This unusual behavior is most probably due to the rather large complexity of the
      systems. From all this emerges the following picture for the charge transport in
      DNA: There is a possibility in short segments of the DNA helix of a Bloch-type
      conduction of holes through the nucleotide base stacks of DNA combined with
      hopping (and in a lesser degree with tunneling). The motivation of this large
      scale computation was that recently in Zurich (ETH) they have performed high
      resolution x-ray diffraction experiments on the structure of the nucleosomes. The
      8 nucleohistones in them are wrapped around by a DNA superhelix of 147 base pairs
      in the DNA B form. The most recent investigations have shown that between the DNA
      superhelix (mostly from its PO(4) (-) groups) there is a charge transfer to the
      positively charged side chains (first of all arginines and lysines) of the
      histones at 120 sites of the superhelix. This would cause a hole conduction in
      DNA and an electronic one in the proteins.

PMID- 18345926
TI  - All-atom level direct folding simulation of a betabetaalpha miniprotein.
AB  - We performed ab initio folding simulation for a betabetaalpha peptide BBA5 (PDB
      code 1T8J) with a modified param99 force field using the generalized Born
      solvation model (param99MOD5/GBSA). For efficient conformational sampling, we
      extended a previously developed novel Q-replica exchange molecular dynamics (Q
      REMD) into a multiplexed Q-REMD. Starting from a fully extended conformation, we
      were able to locate the nativelike structure in the global free minimum region at
      280 K. The current approach, which combines the more balanced force field with
      the efficient sampling scheme, demonstrates a clear advantage in direct folding
      simulation at all-atom level.

PMID- 18345927
TI  - Conformational landscape of the HIV-V3 hairpin loop from all-atom free-energy
      simulations.
AB  - Small beta hairpins have many distinct biological functions, including their
      involvement in chemokine and viral receptor recognition. The relevance of
      structural similarities between different hairpin loops with near homologous
      sequences is not yet understood, calling for the development of methods for de
      novo hairpin structure prediction and simulation. De novo folding of beta strands
      is more difficult than that of helical proteins because of nonlocal hydrogen
      bonding patterns that connect amino acids that are distant in the amino acid
      sequence and there is a large variety of possible hydrogen bond patterns. Here we
      use a greedy version of the basin hopping technique with our free-energy
      forcefield PFF02 to reproducibly and predictively fold the hairpin structure of a
      HIV-V3 loop. We performed 20 independent basin hopping runs for 500 cycles
      corresponding to 7.4 x 10(7) energy evaluations each. The lowest energy structure
      found in the simulation has a backbone root mean square deviation (bRMSD) of only
      2.04 A to the native conformation. The lowest 9 out of the 20 simulations
      converged to conformations deviating less than 2.5 A bRMSD from native.

PMID- 18345928
TI  - The energetics of tetrahydrocarbazole aromatization over Pd(111): a computational
      analysis.
AB  - The carbazole moiety is a component of many important pharmaceuticals including
      anticancer and anti-HIV agents and is commonly utilized in the production of
      modern polymeric materials with novel photophysical and electronic properties.
      Simple carbazoles are generally produced via the aromatization of the respective
      tetrahydrocarbazole (THCZ). In this work, density functional theory calculations
      are used to model the reaction pathway of tetrahydrocarbazole aromatization over
      Pd(111). The geometry of each of the intermediate surface species has been
      determined and how each structure interacts with the metal surface addressed. The
      reaction energies and barriers of each of the elementary surface reactions have
      also been calculated, and a detailed analysis of the energetic trends performed.
      Our calculations have shown that the surface intermediates remain fixed to the
      surface via the aromatic ring in a manner similar to that of THCZ. Moreover, the
      aliphatic ring becomes progressively more planer with the dissociation of each
      subsequent hydrogen atom. Analysis of the reaction energy profile has revealed
      that the trend in reaction barriers is determined by the two factors: (i) the
      strength of the dissociating ring-H bond and (ii) the subsequent gain in energy
      due to the geometric relaxation of the aliphatic ring.

PMID- 18345929
TI  - Differential effects of oligosaccharides on the hydration of simple cations.
AB  - Changed ion hydration properties near surfaces, proteins, and deoxyribose nucleic
      acid have been reported before in the literature. In the present work, we extend
      this work to carbohydrates: We have performed classical-mechanical molecular
      dynamics simulations to study solvation properties of simple cations of
      biological relevance (Na(+),K(+),Mg(2+),Ca(2+)) in explicit water, near single
      and multiple oligosaccharides as glycocalyx models. We find that our
      oligosaccharides prefer direct contact with K(+) over Na(+), but that the Na(+)
      contacts are longer lived. These interactions also lead to strong but short-lived
      changes in oligosaccharide conformations, with oligosaccharides wrapping around
      K(+) with multiple contacts. These findings may have implications for current
      hypotheses on glycocalyx functions.

PMID- 18345930
TI  - Classical and quantum mechanical/molecular mechanical molecular dynamics
      simulations of alanine dipeptide in water: comparisons with IR and vibrational
      circular dichroism spectra.
AB  - We have implemented the combined quantum mechanical (QM)/molecular mechanical
      (MM) molecular dynamics (MD) simulations of alanine dipeptide in water along with
      the polarizable and nonpolarizable classical MD simulations with different models
      of water. For the QM/MM MD simulation, the alanine dipeptide is treated with the
      AM1 or PM3 approximations and the fluctuating solute dipole moment is calculated
      by the Mulliken population analysis. For the classical MD simulations, the solute
      is treated with the polarizable or nonpolarizable AMBER and polarizable CHARMM
      force fields and water is treated with the TIP3P, TIP4P, or TIP5P model. It is
      found that the relative populations of right-handed alpha-helix and extended beta
      and P(II) conformations in the simulation trajectory strongly depend on the
      simulation method. For the QM/MM MD simulations, the PM3/MM shows that the P(II)
      conformation is dominant, whereas the AM1/MM predicts that the dominant
      conformation is alpha(R). Polarizable CHARMM force field gives almost exclusively
      P(II) conformation and other force fields predict that both alpha-helical and
      extended (beta and P(II)) conformations are populated with varying extents.
      Solvation environment around the dipeptide is investigated by examining the
      radial distribution functions and numbers and lifetimes of hydrogen bonds.
      Comparing the simulated IR and vibrational circular dichroism spectra with
      experimental results, we concluded that the dipeptide adopts the P(II)
      conformation and PM3/MM, AMBER03 with TIP4P water, and AMBER polarizable force
      fields are acceptable for structure determination of the dipeptide considered in
      this paper.

PMID- 18345946
TI  - Lipid levels and low-density lipoprotein cholesterol goal attainment in diabetic
      patients: rosuvastatin compared with other statins in usual care.
AB  - OBJECTIVE: To compare change in low-density lipoprotein cholesterol (LDL-C)
      levels and National Cholesterol Education Program (NCEP) Adult Treatment Panel
      III LDL-C goal attainment in diabetic patients treated with rosuvastatin versus
      other statins in a large, managed care health plan. RESEARCH DESIGN AND METHODS:
      This retrospective cohort analysis used medical and pharmacy claims linked to
      laboratory results from a commercial/MedicareAdvantage health plan. Study
      participants were >or= 18 years of age, had a diagnosis of diabetes, were newly
      treated with statins from 8/1/03 to 2/28/05, and were considered at high risk for
      cardiovascular events as defined by NCEP guidelines. Subjects were continuously
      enrolled for 12 months pre-index and >or= 30 days post-index, with variable
      follow-up until therapy discontinuation or end of health plan eligibility. MAIN
      OUTCOME MEASURES: Change in LDL-C from baseline, and attainment of NCEP LDL-C
      goal among patients not at goal before starting therapy. RESULTS: A total of 3337
      adult patients with diabetes were identified with new use of statin therapy
      during the identification period. A total of 9% (n = 301) started on
      rosuvastatin, 49.4% (n = 1,649) on atorvastatin, 20.7% (n = 690) on simvastatin,
      7.0% (n = 234) on pravastatin, 11.7% (n = 391) on lovastatin and 2.2% (n = 72) on
      fluvastatin. After controlling for covariates, rosuvastatin patients experienced
      a significantly greater decrease in LDL-C from baseline (38.7%) than patients
      taking atorvastatin (34.2%) (p = 0.05), simvastatin (31.5%), pravastatin (24.2%),
      fluvastatin (26.3%) or lovastatin (24.9%) (p < 0.0001). Rosuvastatin users were
      significantly more likely to attain LDL-C goal than those taking the other
      statins (odds ratio: 0.44, 0.28, 0.14, 0.14, 0.19, respectively; p < 0.001).
      Predicted percent attaining goal was significantly greater for those taking
      rosuvastatin (87.3%) than for those taking atorvastatin (76.9%), simvastatin
      (68.7%), pravastatin (55.0%), lovastatin (55.3%) or fluvastatin (61.3%) (p <
      0.001). CONCLUSION: For diabetic patients, rosuvastatin is more effective at
      reducing LDL-C levels and attaining NCEP ATP III LDL-C goal than other statins in
      real-world clinical practice.

PMID- 18345948
TI  - Antiretroviral regimens for treatment-experienced patients with HIV-1 infection.
AB  - BACKGROUND: A significant number of treatment-experienced patients with HIV-1
      infection develop drug-resistant virus. OBJECTIVE: To define strategies for
      managing the antiretroviral-experienced patient and summarize current data with
      commonly used drugs for this population. METHODS: This review incorporated data
      from most recent antiretroviral treatment guidelines, published papers on related
      topics, and peer-reviewed publications or presentations at research meetings on
      the safety and efficacy of agents commonly used in this patient population.
      RESULTS/CONCLUSION: The patient experiencing virologic failure on treatment must
      be evaluated for their ability to adhere with therapy and to define the number of
      available active drugs. A viable regimen should include at least two fully active
      agents, with the goal being to achieve complete virologic suppression.

PMID- 18345947
TI  - Warfarin therapy: in need of improvement after all these years.
AB  - BACKGROUND: Warfarin therapy has been used clinically for over 60 years, yet
      continues to be problematic because of its narrow therapeutic index and large
      inter-individual variability in patient response. As a result, warfarin is a
      leading cause of serious medication-related adverse events, and its efficacy is
      also suboptimal. OBJECTIVE: To review factors that are responsible for variable
      response to warfarin, including clinical, environmental, and genetic factors, and
      to explore some possible approaches to improving warfarin therapy. RESULTS:
      Recent efforts have focused on developing dosing algorithms that included genetic
      information to try to improve warfarin dosing. These dosing algorithms hold
      promise, but have not been fully validated or tested in rigorous clinical trials.
      Perhaps equally importantly, adherence to warfarin is a major problem that should
      be addressed with innovative and cost-effective interventions. CONCLUSION:
      Additional research is needed to further test whether interventions can be used
      to improve warfarin dosing and outcomes.

PMID- 18345949
TI  - Combined anti-proliferative and anti-angiogenic strategies for cancer.
AB  - BACKGROUND: In recent years, anti-angiogenic treatments have been shown to
      synergize with traditional chemotherapeutic and radiotherapeutic regimens.
      Combining anti-angiogenesis with targeted anti-proliferative agents might also be
      synergistic. Several lines of evidence point to the validity of this approach,
      and preliminary results of ongoing and recent studies support it. OBJECTIVE: The
      background and current status of anti-angiogenic and anti-proliferative
      treatments will be summarized, as well as the evidence supporting and
      antagonizing their combined use in the clinic. METHODS: Relevant literature was
      reviewed using PubMed search, and recent major conference proceedings and other
      relevant data were searched through internet publications. RESULTS/CONCLUSION:
      Combining anti-angiogenic and anti-proliferative treatments seems a promising
      approach, although not in all clinical circumstances.

PMID- 18345950
TI  - The evaluation and treatment of complicated skin and skin structure infections.
AB  - BACKGROUND: Skin and skin structure infections are frequently encountered in
      clinical practice. Fortunately, these infections usually produce only mild to
      moderate symptoms and signs. Some, however, are severe and may even be life
      threatening. OBJECTIVE: To review the approach to the evaluation and treatment of
      patients with complicated skin and skin structure infections and to discuss when
      to consider using either established antibiotics or recently licensed agents for
      treating these infections. METHODS: In addition to a non-systematic literature
      review of complicated skin and skin structure infections and necrotizing
      fasciitis, we identified recent articles examining the microbiology and
      describing recently licensed antibiotics for treating these infections.
      RESULTS/CONCLUSIONS: Clinicians must learn to recognize the early symptoms and
      signs of severe skin and skin structure infections to ensure they select
      appropriate empiric antibiotic therapy and, when needed, obtain prompt surgical
      consultation. While the recent approvals of new agents for treating these
      infections are welcome, particularly in light of the continued emergence of
      antibiotic-resistant bacteria, traditional antibiotic regimens remain appropriate
      for most cases.

PMID- 18345951
TI  - Eosinophilic esophagitis: management and pharmacotherapy.
AB  - Eosinophilic esophagitis represents the most debated disease of the last 10
      years, too often speculated or overestimated and certainly well known and
      examined. The aim of this study was to summarize the recent therapeutic trends in
      order to show persistent doubts regarding several debated therapies. The study
      combined the most recent international literature and the authors' daily
      experience to define the scope of the review, with limits caused by a lack of
      available randomized studies between dietetic and pharmacological treatment. It
      was concluded that eosinophilic esophagitis is an immunoallergic disease that is
      generally caused by identifiable food and environmental allergens although, in a
      minority of cases, the etiological trigger remains undetermined. Therapy usually
      fights the responsible agents, but sometimes they are not resolved. A need for
      more pathogenetically driven treatments is invoked.

PMID- 18345952
TI  - Ulcerative proctitis: a review of pharmacotherapy and management.
AB  - BACKGROUND: Ulcerative proctitis (UP) is a common presentation of ulcerative
      colitis (UC). OBJECTIVE: To summarize available literature on up-to-date
      management and pharmacotherapy of UP patients. METHODS: Extensive Medline/Embase
      literature search was performed to identify relevant articles.
      RESULTS/CONCLUSION: Topical medication with rectally administered 5
      aminosalicylic acid (5-ASA)/corticosteroid suppositories or enemas is effective
      treatment for most UP patients. Locally administered 5-ASA is more efficacious
      than oral compounds. The combination of topical 5-ASA and oral 5-ASA or topical
      steroids should be considered for escalation of treatment. Maintenance treatment
      is indicated in all UC cases. 5-ASA suppositories are suggested as first-line
      maintenance therapy if accepted by patients, although oral 5-ASA as maintenance
      therapy might prevent proximal extension of the disease. After re-assessment,
      chronically active patients refractory or intolerant to 5-ASAs and
      corticosteroids may require immunomodulators or biological therapy. Exceptional
      cases may require a proctocolectomy.

PMID- 18345953
TI  - Costs, quality of life and treatment compliance associated with antibiotic
      therapies in patients with cystic fibrosis: a review of the literature.
AB  - BACKGROUND: Cystic fibrosis is the most common incurable hereditary disease in
      the US. Persistent respiratory infection is the leading cause of morbidity and
      mortality in cystic fibrosis patients. OBJECTIVE: This study aimed to review the
      literature on economic and quality of life outcomes and treatment compliance
      associated with antibiotic therapies for cystic fibrosis patients. METHODS: A
      systematic literature review was conducted using keyword searches of the MEDLINE
      database and selected conference abstracts. The review covered studies published
      between January 1990 and May 2007. RESULTS/CONCLUSIONS: Evidence suggests that
      inhaled tobramycin, a key chronic suppressive therapy, can reduce other
      healthcare costs. The main determinants of the cost of care include disease
      severity and respiratory infection. Costs vary widely by country. There is
      evidence that inhaled tobramycin and oral azithromycin improve quality of life
      and that treatment setting and patient convenience may also impact on quality of
      life. Antibiotic treatment compliance varied significantly and depended on the
      method of measurement, with more subjective measures tending to be higher. This
      review concludes by offering directions for future research.

PMID- 18345954
TI  - Pharmacological treatment of heterotopic ossification following hip and
      acetabular surgery.
AB  - Heterotopic ossification is a common complication following total hip
      arthroplasty and surgery following acetabular trauma. It is associated with pain
      and a decreased range of movement. Prophylaxis is achieved by either non
      steroidal anti-inflammatory drug treatment or localised irradiation therapy. The
      objective of this study was to evaluate the evidence for pharmacological agents
      used for the prophylaxis of heterotopic ossification following hip and acetabular
      surgery. The study used a comprehensive literature search to identify all major
      clinical studies investigating the pharmacological agents used in the prophylaxis
      of heterotopic ossification following hip and acetabular surgery. It was
      concluded that indometacin remains the 'gold standard' for heterotopic
      ossification prophylaxis following total hip arthroplasty and is the only drug
      proven to be effective against heterotopic ossification following acetabular
      surgery. Following total hip arthroplasty, other non-steroidal anti-inflammatory
      drugs, including naproxen and diclofenac, are equally as effective as indometacin
      and can be considered as alternative first-line treatments. Celecoxib is also of
      equal efficacy to indometacin and is associated with significantly fewer
      gastrointestinal side effects. However, serious concerns were raised over the
      safety of selective cyclooxygenase-2 inhibitors for the cardiovascular system and
      these should be used cautiously.

PMID- 18345955
TI  - Paroxetine.
AB  - BACKGROUND: Paroxetine is a widely used antidepressant that has received
      attention regarding suicide risk in younger patients. OBJECTIVE: The purpose of
      this paper is to review the pharmacology, efficacy and safety of paroxetine in
      the affective disorders. METHODS: The authors performed a PubMed search for all
      literature in English crossing the words 'paroxetine' and 'Paxil' against the
      words 'serotonin transporter,' 'clinical trials,' 'depression' and 'SSRI'. A
      search for paroxetine-related information at the FDA website and under the
      clinical trial register of the GSK website were also performed.
      RESULTS/CONCLUSION: Paroxetine is a serotonin re-uptake inhibitor with good
      selectivity and no significant active metabolites. Paroxetine is approved (ages
      >or= 18 years) for the treatment of major depressive disorder, panic disorder,
      obsessive-compulsive disorder, social anxiety disorder (social phobia), post
      traumatic stress disorder, and generalized anxiety disorders. Drug - drug
      interactions involving the CYP enzyme system have been documented, as well as
      concern for increased suicidality risk in younger adults and recent FDA alerts
      regarding teratogenicity, serotonin syndrome and persistent pulmonary
      hypertension.

PMID- 18345956
TI  - New strategies for the treatment of hyperparathyroidism incorporating
      calcimimetics.
AB  - BACKGROUND: Hyperparathyroidism (HPT), characterised by increased parathyroid
      hormone (PTH) secretion and parathyroid hyperplasia, can be caused by physiologic
      defects in the parathyroid gland (primary HPT [PHPT]) or as a consequence of
      declining renal function (secondary HPT [SHPT]). OBJECTIVE: To review the safety
      and efficacy of cinacalcet in the treatment of SHPT and PHPT. METHODS: Studies
      indexed in NLM/PubMed investigating the safety, efficacy, and pharmacokinetics of
      cinacalcet for PHPT and SHPT and supporting preclinical evidence.
      RESULTS/CONCLUSION: Recent evidence has demonstrated the efficacy of the
      calcimimetic cinacalcet in the treatment of PHPT and SHPT. Compared with
      traditional therapies such as vitamin D sterols and phosphate binders, cinacalcet
      treatment can allow an increased proportion of patients with SHPT to improve
      Kidney Disease Outcomes Quality Initiative (KDOQI) Bone Metabolism and Disease
      laboratory parameter target attainment. Recent evidence suggests that
      improvements in these biochemical parameters with cinacalcet can translate into
      improved morbidity and mortality. Cinacalcet lowers PTH and calcium in patients
      following renal transplantation, and also normalises serum calcium in patients
      with PHPT. Ongoing studies are focusing and future studies are likely to focus on
      the effect of cinacalcet on clinical outcomes and on novel strategies for the
      integration of cinacalcet with traditional therapies to improve serum PTH and
      mineral metabolism control.

PMID- 18345957
TI  - Tamsulosin MR and OCAS (modified release and oral controlled absorption system):
      current therapeutic uses.
AB  - BACKGROUND: Although tamsulosin is mainly used to treat lower urinary tract
      symptoms secondary to benign prostatic hyperplasia, with better understanding of
      functional anatomy and distribution of alpha(1) receptors, it is also indicated
      in other conditions of genito-urinary tract in both men and women. OBJECTIVE: To
      detail the therapeutic use and clinical effects of tamsulosin. METHODS: The scope
      of the review was related to tamsulosin and its therapeutic application in
      conditions of genitourinary tract. Publications were searched from Pubmed and
      Medline from 1975 to 2007 using the search words tamsulosin, lower urinary tract
      symptoms, alpha receptors and blockers. CONCLUSIONS: The management of benign
      prostatic hyperplasia was transurethral resection of prostate until simpler and
      alternative treatments were tried in the last two decades, particularly alpha(1)
      adrenoceptor-blocking agents. Tamsulosin is a potent, third-generation selective
      alpha(1A) adrenoceptor-blocking agent.

PMID- 18345958
TI  - Aliskiren: clinical experience and future perspectives of renin inhibition.
AB  - BACKGROUND: Aliskiren, the first renin inhibitor with sufficient bioavailability
      for oral use, is now available to clinicians treating hypertension. OBJECTIVE:
      The novel mechanism by which aliskiren works was used to provide understanding of
      its therapeutic and adverse effects. METHODS: After reviewing physiology and
      preclinical studies, human studies of aliskiren in hypertension were reviewed.
      Effects of aliskiren on serum levels and enzymatic activity of renin were
      explored. RESULTS/CONCLUSIONS: Aliskiren has antihypertensive efficacy similar to
      existing medications such as thiazide diuretics, angiotensin-converting enzyme
      inhibitors and angiotensin receptor blockers, and can be used in drug
      combinations. Preclinical studies indicate possible cardioprotective and
      renoprotective effects, similar to other inhibitors of the renin-angiotensin
      cascade, but future studies are needed in humans.

PMID- 18345959
TI  - CERA: third-generation erythropoiesis-stimulating agent.
AB  - BACKGROUND: For 20 years, anemia has been treated with erythropoietin-stimulating
      agents (ESA). Until recently there have been only two ESA: recombinant
      erythropoietin and darbepoetin. In 2007 a third agent was approved for clinical
      use, CERA. METHODS: This review covers all of the peer-reviewed literature
      regarding ESA. The review also covers unique aspects of the regulatory
      publications with the FDA and European Agency for the Evaluation of Medicinal
      Products. RESULTS: CERA is effective at correcting renal anemia. Compared to
      previous ESA, CERA has a dramatically lengthened half-life, making it the only
      ESA licensed for once-a-month dosing. However, like the previous ESA, CERA has
      not been shown to reduce morbidity or mortality and has only been shown to
      correct anemia and improve quality of life.

PMID- 18345960
TI  - Photodynamic therapy using 5-aminolaevulinic acid for the treatment of dysplasia
      in Barrett's oesophagus.
AB  - BACKGROUND: 5-Aminolaevulinic acid (ALA) is the naturally occurring metabolic
      precursor of an endogenously formed photosensitiser, protoporphyrin IX. It is
      used topically to treat benign and malignant skin disorders by a process called
      photodynamic therapy (PDT). Recently, data are emerging on its systemic use in
      the treatment of dysplasia in Barrett's oesophagus. OBJECTIVE: To investigate the
      use of ALA-PDT for the treatment of dysplasia and early cancer in Barrett's
      oesophagus. METHODS: A systematic literature review and synopsis is given.
      CONCLUSION: ALA is an attractive alternative to the currently approved
      photosensitiser (porfimer sodium) due to its oral route of administration,
      shorter generalised skin photosensitivity period and lower rate of stricture
      formation. The studies presented demonstrate that ALA-PDT is both safe and
      effective for the treatment of dysplasia and early cancer in Barrett's
      oesophagus.

PMID- 18345961
TI  - A review of the role of levocetirizine as an effective therapy for allergic
      disease.
AB  - BACKGROUND: Levocetirizine is the R-enantiomer of cetirizine dihydrochloride with
      pharmacodynamically and pharmacokinetically favourable characteristics.
      OBJECTIVE: To review the evidence that levocetirizine is an effective therapy for
      allergic disease. METHODOLOGY: Relevant articles in English or with English
      abstracts were identified from systematic PubMed searches. RESULTS:
      Levocetirizine has high bioavailability, high affinity for and occupancy of the
      H1 receptor, rapid onset of action, limited distribution and minimal hepatic
      metabolism. Clinical trials indicate that it is safe and effective for the
      treatment of allergic rhinitis and chronic idiopathic urticaria in adults and
      children with a minimal number of untoward effects. It is also becoming clearer
      that, in addition to its being a potent antihistamine, levocetirizine has several
      anti-inflammatory effects that are observed at clinically relevant concentrations
      that may enhance its therapeutic benefit. Furthermore, there appears to be a
      growing trend for the use of levocetirizine as long-term therapy in addition to
      it being used as a treatment for the immediate short-term manifestations of
      allergic disease. CONCLUSION: Levocetirizine is an effective and safe treatment
      for use in adults and children with allergic disease.

PMID- 18345962
TI  - New indications for topiramate: alcohol dependency and binge-eating disorder.
AB  - BACKGROUND: Topiramate was originally developed as an anti-epileptic but has
      recently been tested in motivated subjects with alcohol dependency and with binge
      eating disorder (BED). METHOD: Evaluation of recent clinical trials. RESULTS: In
      the trial with subjects with alcohol dependency, the primary efficacy outcome was
      the percentage of heavy drinking days, which fell to a greater extent with
      topiramate (from 82 to 40%). In the trial with subjects with BED, the primary
      efficacy measure was weight change. Weight decreased from 98.4 to 97.5 kg in the
      placebo group, and from 96.6 to 89.8 kg in the topiramate group over 21 weeks.
      CONCLUSION: Topiramate may be indicated in alcohol dependency and BED. However,
      it is not known whether benefits with topiramate are retained in the long term,
      nor whether topiramate will be effective in subjects with less resolve.

PMID- 18345963
TI  - Relevance of cortical thickness in migraine sufferers.

PMID- 18345964
TI  - Epstein-Barr virus in the development of multiple sclerosis.

PMID- 18345966
TI  - Escitalopram in the treatment of obsessive-compulsive disorder.
AB  - Obsessive-compulsive disorder (OCD) is a chronic, distressing illness that is
      associated with a specific and unique response to selective serotonin reuptake
      inhibitors. Escitalopram was granted marketing authorization for the treatment of
      OCD from the European authorities in 2007 based on results from two Phase-III
      clinical trials in patients with moderate-to-severe OCD. One, a relapse
      prevention study, demonstrated substantial efficacy of escitalopram 10-20 mg/day
      in both acute and maintenance treatment, and the other demonstrated superior
      efficacy and favorable tolerability of escitalopram compared with placebo during
      24-week, double-blind treatment. These data, and other studies reviewed here,
      suggest that escitalopram is an important additional tool for the treatment of
      OCD.

PMID- 18345967
TI  - DNA-based vaccines: the future of multiple sclerosis therapy?
AB  - Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and
      degenerative disorder of the CNS. Based mostly on work in experimental autoimmune
      encephalomyelitis, CD4(+) T cells were long thought to play the crucial role in
      MS pathogenesis. Only more recently has it been recognized that other effector
      cell types, including CD8(+) T cells, gammadelta-T cells and B lymphocytes may
      also have an important role in disease initiation and perpetuation. The
      expression of soluble inflammatory mediators, including cytokines and free
      radicals, may be one of the late pathways mediating CNS tissue damage. In
      addition, in virtually all patients with MS, an oligoclonal banding pattern of
      antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause
      of MS still remains unknown. Specifically, no single foreign or self antigen has
      been identified to account for clinical disease activity or the presence of
      surrogate disease markers. All approved pharmacotherapies have anti-inflammatory
      or immunoregulatory properties and work in early stages of the disease. In a
      recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin
      basic protein, was tested in patient with MS. BHT-3009 was safe and well
      tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory
      antigen-specific immune changes consisting of a marked decrease in T-cell
      proliferation of IFN gamma production and a reduction in titers of myelin
      specific autoantibodies in the CSF. This review will discuss these intriguing
      observations and the overall potential of DNA vaccination in MS.

PMID- 18345968
TI  - Chronic daily headache.
AB  - The term chronic daily headache (CDH) identifies a heterogeneous group of
      headaches characterized by the presence of daily or near-daily headache,
      including forms associated with medication overuse. This group includes chronic
      (transformed) migraine, chronic tension-type headache, new daily-persistent
      headache and hemicrania continua. According to population studies, CDH affects 4
      5% of the general population worldwide, making it a significant social problem.
      CDH evolves from an episodic form of headache or, more rarely, is daily from
      onset. The classification of CDH continues to be debated, even though the recent
      revision of the diagnostic criteria for several primary headache forms seems to
      have resolved some of the nosographical difficulties. To date, no specific
      therapies have been approved for CDH and there have been few large-scale
      controlled trials of treatments in this area. This article reviews various
      aspects of CDH: classification issues, pathophysiological hypotheses and
      therapeutic (pharmacological and nonpharmacological) approaches.

PMID- 18345969
TI  - Managing headache during pregnancy and lactation.
AB  - Headache patterns for both primary and secondary headaches are often modified in
      women during pregnancy. Although approximately two thirds of women with migraines
      experience headache improvement during pregnancy; women who continue to suffer
      from migraine or other headaches during pregnancy need effective clinical care to
      include appropriate diagnostic studies, counseling about expectations during
      pregnancy and lactation, and modifications in therapeutic regimens to minimize
      risk to the fetus and nursing baby. This review describes the epidemiology of
      headache during pregnancy and lactation, to include both effects of these
      conditions on headache activity and possible concerns about how a maternal
      headache diagnosis may influence the course and outcome of pregnancy. Although
      restrictions in diagnostic testing and medication interventions are often
      necessary during pregnancy and breastfeeding, this review describes evaluation
      and management strategies that provide effective clinical care while minimizing
      risk to the developing baby.

PMID- 18345970
TI  - Pseudotumor cerebri presenting as headache.
AB  - Pseudotumor cerebri (PTC) is characterized by intracranial hypertension without
      ventriculomegaly, in the absence of a mass lesion or meningeal process. When
      there is no secondary cause, it is termed 'idiopathic intracranial hypertension'.
      Headache is the most common symptom of PTC, present in over 90% of patients. The
      headache is often disabling and nonspecific in character; thus, ophthalmoscopy is
      imperative for all patients being evaluated for headache. Visual loss is the
      major morbidity of PTC, requiring prompt diagnosis and treatment to prevent
      permanent deficits. Medical and surgical treatments are employed, although
      evidence-based treatment guidelines do not exist. This review discusses the
      diagnosis, differential diagnosis and management strategies for patients with
      PTC.

PMID- 18345971
TI  - Hypocretins and primary headaches: neurobiology and clinical implications.
AB  - Hypocretins (or orexins) are two neuropeptides synthesized by neurons located
      exclusively in the hypothalamus. Hypocretin-containing neurons have widespread
      projections throughout the CNS; with particularly dense excitatory projections to
      monoaminergic and serotonergic brainstem centers. The hypocretin system
      influences a wide range of physiological processes in mammals, such as feeding,
      arousal, rewards and drug addiction. Recently, a number of studies in
      experimental animals showed that hypocretins are involved in pain modulation
      within the CNS, and suggested the presence of a link between these peptides and
      nociceptive phenomena observed in primary headaches. The aim of this review is to
      describe and discuss recent studies in humans suggesting a role for the
      hypocretin neuronal system in cluster headache and chronic migraine.

PMID- 18345972
TI  - Electrophysiology in demyelinating polyneuropathies.
AB  - Demyelinating neuropathies are disorders of the peripheral nervous system in
      which the myelin sheath of axons is affected by immune-mediated or genetically
      determined processes. In single axons, demyelination yields conduction block due
      to extinction of action potentials or conduction slowing. Motor nerve conduction
      studies assess these phenomena in nerves, which consist of many axons. It is
      important to distinguish demyelinating from axonal polyneuropathies as this
      allows accurate diagnosis and institution of appropriate treatment. Immunological
      treatment in acquired demyelinating polyneuropathies is often successful.
      Criteria were developed for motor conduction velocity slowing and for conduction
      block, which assume demyelination if the findings cannot be explained by axon
      loss. Criteria-sets for the diagnosis of specific polyneuropathies require that
      several variables are consistent with demyelination in several nerves. However,
      these sets are based on expert opinion and have a low sensitivity such that
      treatable neuropathies may be underdiagnosed. Evidence-based sets are currently
      being developed. Axon loss is the main determinant of the clinical deficit in
      demyelinating neuropathies and, if its mechanisms are further elucidated, it may
      be prevented by pharmacological treatment. Excitability testing, which assesses
      axonal membrane potential and ion-channel activities, may reveal some of these
      mechanisms.

PMID- 18345973
TI  - Treating multiple sclerosis with monoclonal antibodies.
AB  - Therapeutic monoclonal antibodies (mAbs) are potent new tools for a molecular
      targeted approach to modify the course of multiple sclerosis (MS). Besides
      natalizumab, which was approved in 2006, three other mAbs (alemtuzumab, rituximab
      and daclizumab) were successfully tested in Phase II MS trials. In this review,
      introductory notes on the development and systematic nomenclature of therapeutic
      mAbs in general, set the stage for a detailed discussion of the four mAbs
      mentioned. We summarize non-MS indications, expression and function of target
      antigens, scientific rationales for MS therapy, putative modes of action and
      pharmacological aspects. Particularly, we provide a critical discussion of
      clinical MS trials, including protocols and interim analyses of trials currently
      underway. The natalizumab section pays special attention to the clinical handling
      of safety issues and the diagnostic use of neutralizing antibodies. We finally
      develop a scenario for how each of the four mAbs might evolve into the market of
      MS therapeutics within the coming years.

PMID- 18345974
TI  - Management of epilepsy in tuberous sclerosis complex.
AB  - Tuberous sclerosis complex (TSC) is an inherited disorder resulting from
      mutations in one of two genes, TSC1 (Hamartin) and TSC2 (Tuberin). These two
      proteins form a cytosolic complex that inhibits the mTOR pathway that controls
      cell growth and proliferation. Pathologically, abnormalities of neuronal
      migration, cellular differentiation and excessive cellular proliferation all
      contribute to the formation of the different brain lesions of TSC. Seizure is the
      most common presenting symptom. Seizures can be present in the first year of life
      and up to one third of children develop infantile spasms. Seizures usually have a
      focal or multifocal origin, are often resistant to antiepileptic drugs and have a
      negative impact on the neurocognitive development. Vigabatrin has proved to be
      effective against infantile spasms due to TSC. New evidence suggests that it is
      possible to noninvasively identify using multimodality techniques, TSC children
      who are likely to become seizure-free following surgical treatment. Understanding
      the mechanisms of epileptogenesis and the possible role of the mTOR pathway in
      this process might increase the availability of novel and targeted therapies.

PMID- 18345975
TI  - Carotid stenting: risk factors for periprocedural stroke.
AB  - Carotid artery stenting is rapidly emerging as a minimally invasive alternative
      to carotid endarterectomy for the treatment of cervical carotid artery occlusive
      disease and stroke prevention. Periprocedural stroke risk still remains a concern
      despite improvements in technique and equipment. We will review technical,
      clinical and radiographic factors associated with an increased risk of stroke
      during carotid artery stenting. The primary focus will be on technical
      proficiency of the interventionalist, patient comorbid conditions (i.e.,
      diabetes, coronary artery disease, renal failure and advanced age) and equipment
      (i.e., embolic protection systems and stent designs) that have been identified in
      the literature as predictors of poorer outcomes.

PMID- 18345976
TI  - Pharmacotherapy and psychotherapy in cannabis withdrawal and dependence.
AB  - Cannabis has long been perceived as a drug causing questionable dependence. Only
      recently has a clinically recognized withdrawal syndrome been described, thus
      laying the foundations for specific treatment evaluations. Six different
      pharmacotherapies have been studied in cannabis withdrawal. Of these, only oral
      tetrahydrocannabinol, and perhaps mirtazapine, have shown some promise in the
      specific treatment of withdrawal symptoms. In cannabis dependence, rimonabant,
      and perhaps buspiron, have shown promising results. Clinical trials of oral
      tetrahydrocannabinol were less convincing. Cognitive and behavioral therapies and
      motivational enhancement therapies have proven their efficacy in several
      randomized controlled trials. Brief therapies have also been associated with good
      compliance and efficacy. Combinations with voucher incentives in certain
      populations have been associated with improved treatment compliance and reduced
      cannabis use. Only two studies have analyzed the cost-efficacy of
      psychotherapies. It would seem that brief combined cognitive and behavioral
      therapies, and motivational enhancement therapies are the most cost effective.
      For the moment, it is uncertain whether the additional treatment costs associated
      with voucher incentives are proportional to the accrued abstinence duration.

PMID- 18345977
TI  - Anxiety and substance use: layers of complexity.
AB  - Anxiety and substance use disorders occur together much more commonly than would
      be expected by chance, as shown in both general population and clinical samples.
      The clinical importance of this is that the outcome for each type of disorder is
      worse across clinical and psychosocial domains than for the disorders that occur
      noncomorbidly. This review explores explanatory models for comorbidity, outlines
      assessment protocols that can be employed in both screening and in treatment
      planning, as well as assessing the efficacy of applied interventions. Treatment
      options are presented, and the evidence base for various psychosocial and
      biological treatments are reviewed.

PMID- 18345978
TI  - The fortunate professor.
AB  - My professional life can be summarized by a quote from the Talmud. Much have I
      learned from my teachers, More from my colleagues, But most from my students. It
      is the fortunate professor who learns from the student.

PMID- 18345979
TI  - Using brain imaging to extract the structure of complex events at the rational
      time band.
AB  - A functional magnetic resonance imaging (fMRI) study was performed in which
      participants performed a complex series of mental calculations that spanned about
      2 min. An Adaptive Control of Thought--Rational (ACT-R) model [Anderson, J. R.
      How can the human mind occur in the physical universe? New York: Oxford
      University Press, 2007] was developed that successfully fit the distribution of
      latencies. This model generated predictions for the fMRI signal in six brain
      regions that have been associated with modules in the ACT-R theory. The model's
      predictions were confirmed for a fusiform region that reflects the visual module,
      for a prefrontal region that reflects the retrieval module, and for an anterior
      cingulate region that reflects the goal module. In addition, the only significant
      deviations to the motor region that reflects the manual module were anticipatory
      hand movements. In contrast, the predictions were relatively poor for a parietal
      region that reflects an imaginal module and for a caudate region that reflects
      the procedural module. Possible explanations of these poor fits are discussed. In
      addition, exploratory analyses were performed to find regions that might
      correspond to the predictions of the modules.

PMID- 18345980
TI  - Fronto-temporal interactions during overt verbal initiation and suppression.
AB  - The Hayling Sentence Completion Task (HSCT) is known to activate left hemisphere
      frontal and temporal language regions. However, the effective connectivity
      between frontal and temporal language regions associated with the task has yet to
      be examined. The aims of the study were to examine activation and effective
      connectivity during the HSCT using a functional magnetic resonance imaging (fMRI)
      paradigm in which participants made overt verbal responses. We predicted that
      producing an incongruent response (response suppression), compared to a congruent
      one (response initiation), would be associated with greater activation in the
      left prefrontal cortex and an increase in the effective connectivity between
      temporal and frontal regions. Fifteen participants were scanned while completing
      80 sentence stems. The congruency and constraint of sentences varied across
      trials. Dynamic Causal Modeling (DCM) and Bayesian Model Selection (BMS) were
      used to compare a set of alternative DCMs of fronto-temporal connectivity. The
      HSCT activated regions in the left temporal and prefrontal cortices, and the
      cuneus. Response suppression was associated with greater activation in the left
      middle and orbital frontal gyri and the bilateral precuneus than response
      initiation. Left middle temporal and frontal regions identified by the
      conventional fMRI analyses were entered into the DCM analysis. Using a systematic
      BMS procedure, the optimal DCM showed that the connection from the left middle
      temporal gyrus, which was driven by verbal stimuli per se, was significantly
      increased in strength during response suppression compared to initiation. Greater
      effective connectivity between left temporal and prefrontal regions during
      response suppression may reflect the transfer of information from posterior
      temporal regions where semantic and lexical information is stored to prefrontal
      regions where it is manipulated in preparation for an appropriate response.

PMID- 18345981
TI  - Attention modulates initial stages of visual word processing.
AB  - Selective attention has the potential to enhance the initial processing of
      objects, their spatial locations, or their constituent features. The present
      study shows that this capacity to modulate initial stages of processing also
      applies to linguistic attributes. A cueing paradigm focused attention at
      different levels of word representations on a trial-by-trial basis to study the
      time course of attentional modulation on visual word processing by means of a
      high-density electrophysiology recording system. Attention to different
      linguistic attributes modulated components related to semantic, phonological, and
      orthographic stages of word processing. Crucially, the N200, associated with
      initial stages of orthographic decoding, was enhanced by attention to the letter
      pattern of words. These results suggest that top-down attention has the capacity
      to enhance initial perceptual stages of visual word processing and support the
      flexibility of attention in modulating different levels of information processing
      depending on task goals.

PMID- 18345983
TI  - Number forms in the brain.
AB  - Abstract Mental images of number lines, Galton's "number forms" (NF), are a
      useful way of investigating the relation between number and space. Here we report
      the first neuroimaging study of number-form synesthesia, investigating 10
      synesthetes with NFs going from left to right compared with matched controls.
      Neuroimaging with functional magnetic resonance imaging revealed no difference in
      brain activation during a task focused on number magnitude but, in a comparable
      task on number order, synesthetes showed additional activations in the left and
      right posterior intraparietal sulci, suggesting that NFs are essentially ordinal
      in nature. Our results suggest that there are separate but partially overlapping
      neural circuits for the processing of ordinal and cardinal numbers, irrespective
      of the presence of an NF, but a core region in the anterior intraparietal sulcus
      representing (cardinal) number meaning appears to be activated autonomously,
      irrespective of task. This article provides an important extension beyond
      previous studies that have focused on word-color or grapheme-color synesthesia.

PMID- 18345982
TI  - Infection, incest, and iniquity: investigating the neural correlates of disgust
      and morality.
AB  - Disgust, an emotion related to avoiding harmful substances, has been linked to
      moral judgments in many behavioral studies. However, the fact that participants
      report feelings of disgust when thinking about feces and a heinous crime does not
      necessarily indicate that the same mechanisms mediate these reactions. Humans
      might instead have separate neural and physiological systems guiding aversive
      behaviors and judgments across different domains. The present interdisciplinary
      study used functional magnetic resonance imaging (n = 50) and behavioral
      assessment to investigate the biological homology of pathogen-related and moral
      disgust. We provide evidence that pathogen-related and sociomoral acts entrain
      many common as well as unique brain networks. We also investigated whether
      morality itself is composed of distinct neural and behavioral subdomains. We
      provide evidence that, despite their tendency to elicit similar ratings of moral
      wrongness, incestuous and nonsexual immoral acts entrain dramatically separate,
      while still overlapping, brain networks. These results (i) provide support for
      the view that the biological response of disgust is intimately tied to
      immorality, (ii) demonstrate that there are at least three separate domains of
      disgust, and (iii) suggest strongly that morality, like disgust, is not a unified
      psychological or neurological phenomenon.

PMID- 18345984
TI  - Dissociation between decoding and reasoning about mental states in patients with
      theory of mind reasoning impairments.
AB  - Theory of mind (ToM) reasoning may involve a multiplicity of processes, including
      an initial stage, where cues relevant for social processes are detected and
      decoded, and a mentalizing stage, where the decoded information is used to reason
      about mental states. Here we report that the processing of lower-order facial
      cues relevant to social judgments can be relatively spared in patients with
      impaired ToM reasoning. We discuss the implications for understanding the
      mechanisms underlying social judgments in brain-lesioned patients.

PMID- 18345985
TI  - Neural mechanisms underlying adaptive actions after slips.
AB  - An increase in cognitive control has been systematically observed in responses
      produced immediately after the commission of an error. Such responses show a
      delay in reaction time (post-error slowing) and an increase in accuracy. To
      characterize the neurophysiological mechanism involved in the adaptation of
      cognitive control, we examined oscillatory electrical brain activity by
      electroencephalogram and its corresponding neural network by event-related
      functional magnetic resonance imaging in three experiments. We identified a new
      oscillatory theta-beta component related to the degree of post-error slowing in
      the correct responses following an erroneous trial. Additionally, we found that
      the activity of the right dorsolateral prefrontal cortex, the right inferior
      frontal cortex, and the right superior frontal cortex was correlated with the
      degree of caution shown in the trial following the commission of an error. Given
      the overlap between this brain network and the regions activated by the need to
      inhibit motor responses in a stop-signal manipulation, we conclude that the
      increase in cognitive control observed after the commission of an error is
      implemented through the participation of an inhibitory mechanism.

PMID- 18345986
TI  - Mid-fusiform activation during object discrimination reflects the process of
      differentiating structural descriptions.
AB  - The present study explored constraints on mid-fusiform activation during object
      discrimination. In three experiments, participants performed a matching task on
      simple line configurations, nameable objects, three dimensional (3-D) shapes, and
      colors. Significant bilateral mid-fusiform activation emerged when participants
      matched objects and 3-D shapes, as compared to when they matched two-dimensional
      (2-D) line configurations and colors, indicating that the mid-fusiform is engaged
      more strongly for processing structural descriptions (e.g., comparing 3-D
      volumetric shape) than perceptual descriptions (e.g., comparing 2-D or color
      information). In two of the experiments, the same mid-fusiform regions were also
      modulated by the degree of structural similarity between stimuli, implicating a
      role for the mid-fusiform in fine differentiation of similar visual object
      representations. Importantly, however, this process of fine differentiation
      occurred at the level of structural, but not perceptual, descriptions. Moreover,
      mid-fusiform activity was more robust when participants matched shape compared to
      color information using the identical stimuli, indicating that activity in the
      mid-fusiform gyrus is not driven by specific stimulus properties, but rather by
      the process of distinguishing stimuli based on shape information. Taken together,
      these findings further clarify the nature of object processing in the mid
      fusiform gyrus. This region is engaged specifically in structural
      differentiation, a critical component process of object recognition and
      categorization.

PMID- 18345987
TI  - Inefficiency in self-organized attentional switching in the normal aging
      population is associated with decreased activity in the ventrolateral prefrontal
      cortex.
AB  - Studies of the aging brain have demonstrated that areas of the frontal cortex,
      along with their associated top-down executive control processes, are
      particularly prone to the neurodegenerative effects of age. Here, we investigate
      the effects of aging on brain and behavior using a novel task, which allows us to
      examine separate components of an individual's chosen strategy during routine
      problem solving. Our findings reveal that, contrary to previous suggestions of a
      specific decrease in cognitive flexibility, older participants show no increased
      level of perseveration to either the recently rewarded object or the recently
      relevant object category. In line with this lack of perseveration, lateral and
      medial regions of the orbito-frontal cortex, which are associated with inhibitory
      control and reward processing, appear to be functionally intact. Instead, a
      general loss of efficient problem-solving strategy is apparent with a concomitant
      decrease in neural activity in the ventrolateral prefrontal cortex and the
      posterior parietal cortex. The dorsolateral prefrontal cortex is also affected
      during problem solving, but age-related decline within this region appears to
      occur at a later stage.

PMID- 18345988
TI  - A developmental examination of amygdala response to facial expressions.
AB  - Several lines of evidence implicate the amygdala in face-emotion processing,
      particularly for fearful facial expressions. Related findings suggest that face
      emotion processing engages the amygdala within an interconnected circuitry that
      can be studied using a functional-connectivity approach. Past work also
      underscores important functional changes in the amygdala during development.
      Taken together, prior research on amygdala function and development reveals a
      need for more work examining developmental changes in the amygdala's response to
      fearful faces and in amygdala functional connectivity during face processing. The
      present study used event-related functional magnetic resonance imaging to compare
      31 adolescents (9-17 years old) and 30 adults (21-40 years old) on activation to
      fearful faces in the amygdala and other regions implicated in face processing.
      Moreover, these data were used to compare patterns of amygdala functional
      connectivity in adolescents and adults. During passive viewing, adolescents
      demonstrated greater amygdala and fusiform activation to fearful faces than did
      adults. Functional connectivity analysis revealed stronger connectivity between
      the amygdala and the hippocampus in adults than in adolescents. Within each
      group, variability in age did not correlate with amygdala response, and sex
      related developmental differences in amygdala response were not found. Eye
      movement data collected outside of the magnetic resonance imaging scanner using
      the same task suggested that developmental differences in amygdala activation
      were not attributable to differences in eye-gaze patterns. Amygdala
      hyperactivation in response to fearful faces may explain increased vulnerability
      to affective disorders in adolescence; stronger amygdala-hippocampus connectivity
      in adults than adolescents may reflect maturation in learning or habituation to
      facial expressions.

PMID- 18345989
TI  - The left posterior superior temporal gyrus participates specifically in accessing
      lexical phonology.
AB  - Impairments in phonological processing have been associated with damage to the
      region of the left posterior superior temporal gyrus (pSTG), but the extent to
      which this area supports phonological processing, independent of semantic
      processing, is less clear. We used repetition priming and neural repetition
      suppression during functional magnetic resonance imaging (fMRI) in an auditory
      pseudoword repetition task as a semantics-free model of lexical (whole-word)
      phonological access. Across six repetitions, we observed repetition priming in
      terms of decreased reaction time and repetition suppression in terms of reduced
      neural activity. An additional analysis aimed at sublexical phonology did not
      show significant effects in the areas where repetition suppression was observed.
      To test if these areas were relevant to real word production, we performed a
      conjunction analysis with data from a separate fMRI experiment which manipulated
      word frequency (a putative index of lexical phonological access) in picture
      naming. The left pSTG demonstrated significant effects independently in both
      experiments, suggesting that this area participates specifically in accessing
      lexical phonology.

PMID- 18345990
TI  - Cerebellar transcranial direct current stimulation impairs the practice-dependent
      proficiency increase in working memory.
AB  - How the cerebellum is involved in the practice and proficiency of non-motor
      functions is still unclear. We tested whether transcranial direct current
      stimulation (tDCS) over the cerebellum (cerebellar tDCS) induces after-effects on
      the practice-dependent increase in the proficiency of a working memory (WM) task
      (Sternberg test) in 13 healthy subjects. We also assessed the effects of
      cerebellar tDCS on visual evoked potentials (VEPs) in four subjects and compared
      the effects of cerebellar tDCS on the Sternberg test with those elicited by tDCS
      delivered over the prefrontal cortex in five subjects. Our experiments showed
      that anodal or cathodal tDCS over the cerebellum impaired the practice-dependent
      improvement in the reaction times in a WM task. Because tDCS delivered over the
      prefrontal cortex induced an immediate change in the WM task but left the
      practice-dependent proficiency unchanged, the effects of cerebellar tDCS are
      structure-specific. Cerebellar tDCS left VEPs unaffected, its effect on the
      Sternberg task therefore seems unlikely to arise from visual system involvement.
      In conclusion, tDCS over the cerebellum specifically impairs the practice
      dependent proficiency increase in verbal WM.

PMID- 18345991
TI  - The sense of touch: embodied simulation in a visuotactile mirroring mechanism for
      observed animate or inanimate touch.
AB  - Previous studies have shown a shared neural circuitry in the somatosensory
      cortices for the experience of one's own body being touched and the sight of
      intentional touch. Using functional magnetic resonance imaging (fMRI), the
      present study aimed to elucidate whether the activation of a visuotactile
      mirroring mechanism during touch observation applies to the sight of any touch,
      that is, whether it is independent of the intentionality of observed touching
      agent. During fMRI scanning, healthy participants viewed video clips depicting a
      touch that was intentional or accidental, and occurring between animate or
      inanimate objects. Analyses showed equal overlapping activation for all the touch
      observation conditions and the experience of one's own body being touched in the
      bilateral secondary somatosensory cortex (SII), left inferior parietal lobule
      (IPL)/supramarginal gyrus, bilateral temporal-occipital junction, and left
      precentral gyrus. A significant difference between the sight of an intentional
      touch, compared to an accidental touch, was found in the left primary
      somatosensory cortex (SI/Brodmann's area [BA] 2). Interestingly, activation in
      SI/BA 2 significantly correlated with the degree of intentionality of the
      observed touch stimuli as rated by participants. Our findings show that
      activation of a visuotactile mirroring mechanism for touch observation might
      underpin an abstract notion of touch, whereas activation in SI might reflect a
      human tendency to "resonate" more with a present or assumed intentional touching
      agent.

PMID- 18345992
TI  - Error negativity does not reflect conflict: a reappraisal of conflict monitoring
      and anterior cingulate cortex activity.
AB  - Our ability to detect and correct errors is essential for our adaptive behavior.
      The conflict-loop theory states that the anterior cingulate cortex (ACC) plays a
      key role in detecting the need to increase control through conflict monitoring.
      Such monitoring is assumed to manifest itself in an electroencephalographic (EEG)
      component, the "error negativity" (Ne or "error-related negativity" [ERN]). We
      have directly tested the hypothesis that the ACC monitors conflict through
      simulation and experimental studies. Both the simulated and EEG traces were
      sorted, on a trial-by-trial basis, as a function of the degree of conflict,
      measured as the temporal overlap between incorrect and correct response
      activations. The simulations clearly show that conflict increases as temporal
      overlap between response activation increases, whereas the experimental results
      demonstrate that the amplitude of the Ne decreases as temporal overlap increases,
      suggesting that the ACC does not monitor conflict. At a functional level, the
      results show that the duration of the Ne depends on the time needed to correct
      (partial) errors, revealing an "on-line" modulation of control on a very short
      time scale.

PMID- 18345993
TI  - An assessment of the ocular safety of inactive excipients following sub-tenon
      injection in rabbits.
AB  - PURPOSE: This work characterized the safety and toleration of inactive excipients
      following sub-Tenon (ST) administration. METHODS: Rabbits were anesthetized and
      eyes received an ST injection of the following test excipients: carboxy
      methylcellulose (CMC; low [90 kDa], mid [250 kDa], and high [700 kDa] molecular
      weight [MW], 0.25%-1.0% w/v), polysorbate 80 (0.02 and 0.2% w/v), polyethylene
      glycol 3350 (PEG; 0.2 and 1.0% w/v), poloxamer 188 (0.01 and 0.25% w/v),
      poloxamer 182 (2% w/v), benzyl alcohol (BA; 4% w/v), benzalkonium chloride (BAC;
      0.02%, 0.04%, and 0.05% w/v), and methylcellulose (MC; 0.25% w/v). After a 1-week
      observation period for clinical signs of ocular tolerability, the animals were
      euthanized and eyes were collected for histologic examination. RESULTS: The
      ocular tolerability of the tested excipients were ranked as follows from the
      innocuous to most deleterious: saline approximately PEG (1% w/v) approximately
      polysorbate 80 (0.2% w/v) > CMC (0.25% w/v, 90 kDa) > MC (0.25% w/v)
      approximately poloxomer 188 (0.25% w/v) approximately sodium citrate (pH 9) BAC
      (0.05% w/v) > CMC (0.5% w/v, 700 kDa) > poloxomer 182 (2% w/v) > BA (4% w/v).
      Clinical signs of ocular irritation were limited to redness and chemosis observed
      with most test excipients. The BA excipient also produced corneal opacity.
      Microscopic findings included histiocytic infiltration (BAC, BA, CMC, MC, and
      poloxamer 188), heterophilic inflammation (BA, CMC, and poloxamer 182), and edema
      (BAC, BA, CMC, and poloxamer 182) in episcleral tissue. The severity of the
      clinical and hisopathologic effects increased with the concentration of the test
      excipients administered. CONCLUSIONS: This research has evaluated the safety
      profile of inactive excipients that may be used to formulate new chemical
      entities for the treatment of ocular disease following a ST injection.

PMID- 18345994
TI  - Coronary heart disease risk and bone mineral density among U.S. women and men.
AB  - AIMS: Low bone mineral density (BMD) has been shown to predict cardiovascular
      disease (CVD) and coronary heart disease (CHD) mortality in both women and men.
      The purpose of the current study was to determine whether a CHD risk assessment
      tool might be useful for identifying persons likely to have low BMD in a
      multiethnic population of women and men. METHODS: Cross-sectional data for 3881
      women and men aged 50-74 years without overt CHD or stroke from the Third
      National Health and Nutrition Examination Survey (NHANES III) were used to
      explore the relationship between BMD and 10-year CHD risk, as estimated using the
      Framingham CHD risk prediction algorithm, in gender-stratified multiple logistic
      regression models. RESULTS: When compared with women who had a <10% CHD risk,
      women with a 10%-19% CHD risk were 45% more likely and those with a > or =20% CHD
      risk were 73% more likely to have low BMD. Similar increases in low BMD risk were
      not detected in men. CONCLUSIONS: In the United States, 10-year Framingham CHD
      risk assessment may be useful for identifying older women who should be evaluated
      for osteoporosis and referred for BMD measurement. The impact of such a screening
      strategy on fracture prevention needs further elucidation.

PMID- 18345995
TI  - Screening for depression in the postpartum period: a comparison of three
      instruments.
AB  - OBJECTIVES: Postpartum depression, the most prevalent complication of childbirth,
      is often unrecognized. Our objective was to compare the effectiveness of three
      screening instruments--Edinburgh Postnatal Depression Scale (EPDS), Patient
      Health Questionnaire (PHQ-9), and the 7-item screen of the Postpartum Depression
      Screening Scale (PDSS)--for identifying women with postpartum depression in the
      first 6 months after delivery. METHODS: We administered the three instruments via
      telephone to women who were > or =18 years and had delivered infants 6-8 weeks
      earlier. We arranged home interviews to confirm DSM-IV criteria current major
      depressive disorder (MDD) in women who had an above-threshold score on any of the
      instruments. For women who screened negative on the 6-8 week call, we repeated
      the screening at 3 months and 6 months to identify emergent symptoms. The primary
      outcome measures were the screening scores and DSM-IV diagnoses. RESULTS: Of 135
      women reached, 123 (91%) were screened, 29 (24%) had home visits, and 13 (11%)
      had an MDD within 6 months of delivery. Analyses of the scores at 6-8 weeks
      postpartum and the DSM-IV diagnoses indicated the EPDS at a cutoff point of > or
      =10 identified 8 (62%) of cases, the PHQ-9 at a cutoff point of > or =10
      identified 4 (31%), and the PDSS 7-item Short Form (PDSS_SF) at a cutoff point of
      > or =14 identified 12 (92%). However, 15 of 16 (94%) women without current MDD
      screened positive on the PDSS_SF. The EPDS was significantly more accurate (p =
      0.01) than the PDSS_SF and PHQ-9 with the cutoff points used. After correcting
      for verification bias, we found the EPDS and the PDSS_SF were significantly more
      accurate than the PHQ-9 (p < 0.03). CONCLUSIONS: Administering the EPDS by phone
      at 6-8 weeks postpartum is an efficient and accurate way to identify women at
      high risk for postpartum depression within the first 6 months after delivery.

PMID- 18345996
TI  - Grief following miscarriage: a comprehensive review of the literature.
AB  - OBJECTIVE: The literature exploring the relationship between miscarriage and
      grief is sparse. This paper summarizes the literature on grief subsequent to an
      early miscarriage to elucidate the nature, incidence, intensity, and duration of
      grief at this time and to identify potential moderators. METHODS: An electronic
      search of the Medline and Psych Info databases was conducted. Studies were
      selected for inclusion if they related to early miscarriage, used a standardized
      measure to assess perinatal grief, and specified the assessment intervals
      employed. Qualitative studies were included when helpful to develop hypotheses.
      RESULTS: Descriptions of grief following miscarriage are highly variable but tend
      to match descriptions of grief used to characterize other types of significant
      losses. A sizable percentage of women seem to experience a grief reaction, with
      the actual incidence of grief unclear. Suggestively, grief, when present, seems
      to be similar in intensity to grief after other types of major losses and is
      significantly less intense by about 6 months. Few conclusions can be drawn in
      regard to potential moderators of grief following a miscarriage. CONCLUSIONS:
      Although additional research is clearly needed, guidelines for coping with grief
      following miscarriage can be based on the data available on coping with other
      significant types of losses. Given the range of potential meanings for this
      primarily prospective and symbolic loss, practitioners need to encourage patients
      to articulate the specific nature of their loss and assist in helping them
      concretize the experience.

PMID- 18345997
TI  - Smoking during pregnancy and postpartum: smoking rates and intention to quit
      smoking or resume after pregnancy.
AB  - BACKGROUND: A substantial number of women smoke while pregnant. The majority of
      those who quit return to smoking within 12 months. The aim of this study is to
      estimate smoking rates and to measure the urge to smoke and the motivation to
      change smoking behavior among women who recently delivered. METHODS: Data
      presented stem from two studies. Study 1 is an epidemiological survey
      investigating the health of neonates. Study 2 presents screening data of an
      efficacy trial for a smoking cessation and relapse prevention intervention.
      Participants were recruited on maternity wards within 7 days after delivery.
      RESULTS: Five hundred fifty-three (29.1%) women were never smokers, 145 (7.6%)
      were former smokers, 492 (25.9%) abstained during pregnancy, and 712 (37.4%)
      smoked throughout pregnancy. Of the smokers, 69% did not intend to quit smoking
      within the next 6 months. Of the women who quit during pregnancy, 80% did not
      want to resume smoking within the next 6 months or after weaning. CONCLUSIONS:
      Smoking and relapse rates indicate a need for increased efforts to reduce smoking
      during pregnancy and postpartum. Reported intention to quit or resume does not
      reflect the high number of relapses. Indicators for relapse need to be found.

PMID- 18345998
TI  - The frequency and distribution of cardiovascular disease risk factors among
      Nebraska women enrolled in the WISEWOMAN screening program.
AB  - OBJECTIVES: To examine cardiovascular disease (CVD) risk factors and changes in
      the 10-year coronary heart disease (CHD) risk factors in women who participated
      in the WISEWOMAN program in Nebraska. METHODS: Data for analysis were available
      for a total of 10,739 women who received CVD screening between September 2002 and
      December 2004. We examined the relationships between sociodemographic
      characteristics and CVD risk factors, including high cholesterol, high blood
      pressure, high body mass index (BMI), and diabetes. Additionally, we assessed the
      10-year CHD risk and the change in risk factors for CVD. RESULTS: The incidence
      was 31 per 1000 for hyperglycemia, 66 per 1000 for hypertension, and 157 per 1000
      for high cholesterol. The prevalence of obesity was 447 per 1000. Nonwhite,
      older, less educated, and rural women were more likely to be overweight or obese.
      Older, less educated, and overweight to obese women were more likely to have
      hyperglycemia and high blood pressure. Older and overweight to obese women were
      more likely to have high total cholesterol and an increased 10-year CHD risk.
      CONCLUSIONS: Race, age, and rural residence were related to CVD risk factors
      among low-income women in Nebraska. The effect of program eligibility
      requirements as a barrier to return visits should be more closely examined, and
      strategies to facilitate repeat screenings on WISEWOMAN projects should be
      undertaken. Additionally, women on the lower end of the socioeconomic spectrum
      were less likely to return for repeat visits, suggesting that further
      investigation is needed to understand why these women fail to return for
      screening services.

PMID- 18345999
TI  - Gender differences in utilization of effective cardiovascular secondary
      prevention: a Cleveland clinic prevention database study.
AB  - BACKGROUND: Previous studies have suggested that women with cardiovascular
      disease may receive less aggressive care than men. Using a large cardiology
      database from a tertiary referral center, we sought to determine if treatment
      differences still persist in the current era. METHODS: We analyzed data on 2462
      patients who were referred for secondary prevention to the Preventive Cardiology
      Clinic at The Cleveland Clinic Foundation between 1997 and 2004. The primary
      objective was to evaluate use of effective secondary preventive therapies, by
      gender, as outlined in the ACC/AHA guidelines, such as antiplatelet therapy, beta
      blockers, statins, and angiotensin-converting enzyme (ACE) inhibitors.
      Multivariate logistic regression analysis was performed to assess the independent
      effect of gender on all cause mortality. RESULTS: Women were older (62.2 +/- 11.1
      vs. 59.4 +/- 11.0, p < 0.001) and more likely to be hypertensive (68.1% vs.
      56.1%, p < 0.001) than men. Overall, women were more likely than men to have
      higher baseline C-reactive protein (CRP) (6.14 +/- 13.4 vs. 4.9 +/- 10.7, p <
      0.001), low-density lipoprotein cholesterol (LDL-C) (135 +/- 66 vs. 116 +/- 46, p
      < 0.001), high-density lipoprotein cholesterol (HDL-C) (52 +/- 17 vs. 41 +/- 11,
      p < 0.001), and total cholesterol (238 +/- 98 vs. 202 +/- 65, p < 0.001). Women
      were less likely to be on antiplatelet therapy (76.6 % vs. 85.0%, p < 0.001) and
      statins or any lipid-lowering therapy (62.6% vs. 67.1%, p = 0.04) compared with
      men on presentation. CONCLUSIONS: Even in the current era, women with established
      cardiovascular disease continue to receive less aggressive care than men. They
      are less likely to be on aspirin and statin therapy. More aggressive efforts
      should be made to treat both men and women with standard secondary preventive
      efforts.

PMID- 18346000
TI  - Disparities in the provision of sexually transmitted disease and pregnancy
      testing and prophylaxis for sexually assaulted women in Rhode Island emergency
      departments.
AB  - OBJECTIVES: To determine how often sexually assaulted adult female emergency
      department (ED) patients are being offered testing and prophylaxis for sexually
      transmitted diseases (STDs) and pregnancy and identify factors associated with
      the offering of tests and prophylaxis. METHODS: This is a retrospective study of
      ED visits for adult female sexual assault in all Rhode Island EDs from January
      1995 through June 2001. The percentage of patients offered testing and
      prophylaxis was calculated. Multivariable logistic regression was used to
      identify factors related to testing and prophylaxis use for women sustaining an
      anal/vaginal assault. RESULTS: Of the 780 patients, 78.2% sustained anal/vaginal
      penetration, 5.0% genital touching only, and 3.7% oral sex only, and 13.1% did
      not know what happened to them. Of those women anal/vaginally assaulted, 83.8%
      were offered chlamydia/gonorrhea testing, 69.4% syphilis testing, 82.9% pregnancy
      testing, 77.0% chlamydia/gonorrhea prophylaxis, 47.6% emergency contraception,
      and 19.2% HIV prophylaxis. In multivariable logistic regression models, patients
      evaluated at the state's women's hospital instead of academic or community
      hospitals and those who sustained anal/vaginal assault instead of other assaults
      had a greater odds of being offered testing and prophylaxis. In some cases, older
      women were offered testing and prophylaxis less often than younger women.
      CONCLUSIONS: Testing and prophylaxis for chlamydia/gonorrhea were used much more
      often than prophylaxis for emergency contraception and HIV, even for patients who
      were anal/vaginally assaulted. Disparities in testing and prophylaxis exist by
      type of hospital and, in some cases, by age. Educational campaigns should be
      instituted to ensure that all women receive adequate testing and prophylaxis
      commensurate with the exposure they sustained from a sexual assault.

PMID- 18346001
TI  - Cervical cancer screening among Thai women in Northern California.
AB  - OBJECTIVES: Cervical cancer is the leading cause of cancer for Thai women in
      Thailand, but little is known about the cancer screening practices of Thai
      immigrants in the United States. This study explores factors that influence
      cervical cancer screening behavior among Thai women in California. METHODS: In
      2003, face-to-face interviews were conducted in Northern California among Thai
      women age > or = 18 years. Surveys collected information on use and adherence to
      Pap tests, demographic characteristics, access to healthcare variables, enabling
      factors, and knowledge of and attitude toward cervical cancer and screening.
      RESULTS: Among the 322 women included in the study, 74% were ever screened and
      61% were screened within the last 3 years (adherent) for cervical cancer. Having
      a doctor's recommendation was significantly associated with ever having and
      recently having a Pap test. Insurance status, language most used, and selected
      knowledge and enabling variables were also predictors of Pap screening.
      CONCLUSIONS: The Pap testing rates for Thai women in our sample were lower than
      national guidelines. Interventions should be targeted toward improving access to
      screening (especially for first-time screeners), enhancing culturally appropriate
      patient-physician interactions to promote screening, deemphasizing sexual
      activity, and increasing knowledge about cervical cancer causes for Thai women in
      the United States.

PMID- 18346002
TI  - Post-operative expansion of hemorrhagic contusions after unilateral decompressive
      hemicraniectomy in severe traumatic brain injury.
AB  - Decompressive hemicraniectomy is commonly performed in patients with traumatic
      brain injury (TBI) with diffuse brain swelling or refractory raised intracranial
      pressure. Expansion of hemorrhagic contusions in TBI patients is common, but its
      frequency following decompressive hemicraniectomy has not been well established.
      The aim of this retrospective study was to determine the rate of hemorrhagic
      contusion expansion following unilateral hemicraniectomy in severe TBI, to
      identify factors associated with contusion expansion, and to examine whether
      contusion expansion is associated with worsened clinical outcomes. Computed
      tomography (CT) scans of 40 consecutive patients with non-penetrating TBI who
      underwent decompressive hemicraniectomy were analyzed. Hemorrhagic contusion
      volumes were measured on initial, last pre-operative, and first post-operative CT
      scans. Mortality and 6-month Glasgow Outcome Scale (GOS) score were recorded.
      Hemorrhagic contusions of any size were present on the initial head CT scan in
      48% of patients, but hemorrhagic contusions with a total volume of >5 cc were
      present in only 10%. New or expanded hemorrhagic contusions of >or=5 cc were
      observed after hemicraniectomy in 58% of patients. The mean volume of increased
      hemorrhage among these patients was 37.1+/-36.3 cc. The Rotterdam CT score on the
      initial head CT was strongly associated with the occurrence and the total volume
      of expanded hemorrhagic contusions following decompressive hemicraniectomy.
      Expanded hemorrhagic contusion volume greater than 20 cc after hemicraniectomy
      was strongly associated with mortality and poor 6-month GOS even after
      controlling for age and initial Glasgow Coma Scale (GCS) score. Expansion of
      hemorrhagic contusions is common after decompressive hemicraniectomy following
      severe TBI. The volume of hemorrhagic contusion expansion following
      hemicraniectomy is strongly associated with mortality and poor outcome. Severity
      of initial CT findings may predict the risk of contusion expansion following
      hemicraniectomy, thereby identifying a subgroup of patients who might benefit
      from therapies aimed at augmenting the coagulation system.

PMID- 18346003
TI  - Construction and preliminary investigation of a plasmid containing a novel
      immunotoxin DT390-IL-18 gene for the prevention of murine experimental autoimmune
      encephalomyelitis.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a neuropathological animal
      model for multiple sclerosis. Antigen-presenting cells (APCs) expressing
      interleukin-18 receptor (IL-18R) were shown to be crucial in the beginning and
      progress of EAE. In this study we tested the effect of a novel recombinant
      immunotoxin targeting IL-18R-bearing APC for EAE prevention. The novel eukaryotic
      plasmid DT390-IL-18-SRalpha, encoding recombinant immunotoxin DT390-IL-18, was
      constructed. The immunotoxin consisted of IL-18 as the targeting moiety, and a
      truncated diphtheria toxin (DT) as the toxic moiety. Transfection assay and
      proliferation inhibition assay proved the immunotoxin could be expressed in vitro
      and was toxic to the activated mouse T cells. To evaluate the preventive effect
      of DT390-IL-18-SRalpha on EAE in vivo, cationic liposome-embedded DT390-IL-18
      SRalpha was injected into the hind limbs of EAE mice. DT390-IL-18-SRalpha-treated
      mice showed a delayed manifestation of EAE and decreased symptoms compared to the
      mice treated with plasmid DT390-SRalpha or phosphate-buffered saline alone. A
      significant reduction in infiltrating inflammatory cells was detected in the
      brain tissues from immunotoxin-treated mice as compared with the controls by
      hematoxylin-eosin staining. This study suggested that the recombinant immunotoxin
      DT390-IL-18 could be expressed in vitro and in vivo, and prevented murine EAE
      effectively.

PMID- 18346004
TI  - Primary leiomyosarcoma of the thyroid gland.
AB  - Primary leiomyosarcomas of the thyroid gland are rare. We present the case of a
      65-year-old woman with a rapidly enlarging neck mass for 2 months. The
      preoperative differential diagnosis included medullary thyroid cancer, anaplastic
      thyroid cancer, and primary versus metastatic sarcoma. The patient underwent
      total thyroidectomy, bilateral central neck dissections, and cervical thymectomy;
      she is currently being treated with ifosfamide and adriamycin. We review the
      literature on leiomyosarcoma of the thyroid, including the differential
      diagnoses, pathology, and alternative treatment strategies, including surgery and
      adjuvant therapy.

PMID- 18346005
TI  - Introducing the thyroid gland as another victim of the insulin resistance
      syndrome.
AB  - BACKGROUND: Insulin is a thyroid growth factor that stimulates proliferation of
      thyroid cells in culture. In order to evaluate the effects of insulin resistance
      (IR) on the thyroid gland, we developed a prospective study in euthyroid women.
      METHODS: One hundred eleven women (mean age 32.2 +/- 7 years) were evaluated by a
      thyroid ultrasound (US) and basal and postprandial serum insulin. Subjects were
      divided into four groups as follows: G1 (n = 42), subjects with IR and obesity;
      G2 (n = 21), subjects with obesity without IR; G3 (n = 17), subjects with IR and
      normal weight; and G4 (n = 31) control group (without IR and obesity). RESULTS:
      The thyroid volume (TV), measured by US, showed the following values: G1, 17 +/-
      3 mL; G2, 13.8 +/- 2.8 mL; G3, 16.2 +/- 2.1 mL; and G4,12.1 +/- 2.4 mL. There was
      no significant difference in TV between G1 and G3, but differences between G1 and
      G2, and between G3 and G4 were significant at p < 0.05. The percentage of nodular
      thyroid glands observed by US in each group was as follows: G1, 50%; G2, 23.8%;
      G3, 61%; G4, 16.1%. Again, the differences between G1 and G2 and between G3 and
      G4 were statistically significant (p < 0.005 and p < 0.001, respectively, for
      each comparison). CONCLUSIONS: It is concluded that the higher circulating levels
      of insulin cause increased thyroid proliferation. The clinical manifestations are
      the larger thyroid volume and the formation of nodules. Thus, the thyroid gland
      appears to be another victim of the insulin resistance syndrome.

PMID- 18346006
TI  - Modified approach for lingual thyroid transposition: report of two cases.
AB  - Lingual thyroid is a rare congenital anomaly of thyroid development resulting
      from failure of the thyroglossal duct to migrate from the foramen cecum to the
      prelaryngeal site. The lingual thyroid associated with a fetal adenoma is even
      more unusual. We presented two cases of lingual thyroid, one associated with
      fetal adenoma. The ectopic gland was transposed into the muscle space at the
      floor of the mouth using an extraoral midline lower lip, mandible and tongue
      splitting approach in case 1, and a transoral lower lip degloving and midline
      mandibulotomy and tongue-splitting approach in case 2. Sixteen-year follow-up of
      case 1 and 6-month follow-up of case 2 showed that the transposed thyroids
      achieved normal function. Case 2 had no visible scar in the lower lip and mental
      area. Surgical transposition of the lingual thyroid to the floor of the mouth
      with the vascular supply intact offers a promising approach for the treatment of
      this anomaly. The transoral lower lip degloving and midline-splitting approach is
      recommended because of its better cosmetic outcome.

PMID- 18346007
TI  - Nonfunctioning parathyroid cancer presenting as a cervical mass.

PMID- 18346008
TI  - Decrease in bacterial load versus resistance selection of pneumococcal
      subpopulations by beta-lactam physiological concentrations over time: an in vitro
      pharmacodynamic simulation.
AB  - To investigate beta-lactam effects on Streptococcus pneumoniae-mixed cultures, a
      computerized pharmacodynamic model simulating over 24-hr concentrations obtained
      after several beta-lactam regimens was used. Strain 1 (no penicillin binding
      protein [PBP] mutations) and strain 2 (mutation in pbp1a) were
      penicillin/amoxicillin susceptible. Strain 3 (mutations in pbp1a, pbp2x, and
      pbp2b) and strain 4 (mutations in pbp1a, pbp2x, and pbp2b [10 changes]) were
      penicillin/amoxicillin resistant. Initial inoculum was approximately 6 x 10(6)
      CFU (colony forming units)/ml (with a 1:1:1:1 proportion of each strain).
      Population analysis profile was performed pre- and post-simulations. Strain 1
      exhibited the best fitness (growth over 24 hr) in individual cultures, and strain
      2 did so in mixed cultures in antibiotic-free simulations. In antibiotic
      simulations with the mixed inocula, penicillin/amoxicillin-susceptible strains
      were eradicated with all study drugs (time that concentrations exceed the minimal
      inhibitory concentration [T>MIC >or= 43%]). Penicillin-resistant strains showed
      different evolution depending on the antibiotic: (a) cefditoren produced >2
      log(10) reduction of initial inocula at 12-24 hr (T>MIC >or=45%), with a
      remaining population growing in plates with >or=4 mg/L amoxicillin; (b)
      cefuroxime, cefixime, and cefaclor did not decrease initial inocula at 12-24 hr
      (T>MIC=0%), with minor subpopulations growing in plates with 4 mg/L amoxicillin;
      (c) amoxicillin produced 2.6 log(10) decrease of initial inocula at 12 hr
      (T>MIC=47.5%), but 1.1 log(10) increase of initial inocula at 24 hr, with a
      significant population growing in plates with 4 mg/L amoxicillin. Antibiotic
      activity against mixed inocula (susceptible and resistant strains) depends on
      intrinsic activity (as well as its subsequent pharmacodynamic activity: T>MIC
      against resistant strains), and on possible selection of intra-strain-resistant
      subpopulations.

PMID- 18346009
TI  - Identification of the first vancomycin intermediate-resistant Staphylococcus
      aureus (VISA) isolate from a hospital in Portugal.
AB  - A clinical isolate of methicillin-resistant Staphylococcus aureus (MRSA) with
      intermediate resistance to vancomycin (minimal inhibitory concentration [MIC] of
      4 mug/ml) was isolated in 2006 from a surgical wound of a patient hospitalized at
      the orthopedics ward of Hospital de Sao Marcos--Braga, in the town of Braga. A
      combination of molecular typing methods, including pulsed-field gel
      electrophoresis (PFGE), spa typing, multilocus sequence typing, and
      staphylococcal chromosomal cassette mec typing, identified the vancomycin
      intermediate-resistant S. aureus VISA-BRAGA as a derivative of the epidemic MRSA
      (EMRSA)-15 clone, which has been isolated with increasing frequency from several
      Portuguese hospitals recently. Compared to another EMRSA-15 isolate with the same
      genetic background (including PFGE subtype) the VISA-BRAGA isolate exhibited
      relatively high oxacillin MIC, slow growth, loss of hemolytic activity, and
      increased resistance to vancomycin and to daptomycin although neither of these
      two antibiotics was used in therapy. The VISA-BRAGA isolate described here
      appears to represent the first S. aureus with decreased susceptibility to
      vancomycin identified in a Portuguese hospital.

PMID- 18346010
TI  - Characterization of Staphylococcus aureus nasal carriage from children attending
      an outpatient clinic in Seoul, Korea.
AB  - Nasal swabs were collected to isolate S. aureus in 296 children, who visited the
      pediatrics department with a variety of symptoms. Staphylococcus aureus was
      isolated from 95 children (32.1%). Of the isolates, 18 were methicillin-resistant
      S. aureus (MRSA) (18.9%). Antimicrobial susceptibility testing was performed for
      all S. aureus cultured and the molecular characteristics were investigated. Forty
      nine spa types were identified among the S. aureus isolates, and were classified
      into 13 spa groups (A-L). The most prevalent clone (34 isolates, 35.8%) belonged
      to the spa group B (spa repeat motif, WG/FKAOMQ), which corresponded to sequence
      type 30 (ST30) and its variants. Sixteen different spa types, within the spa
      group B, suggested that this group has evolved over a long period of time. In
      addition, all S. aureus isolates belonging to the spa group B were methicillin
      susceptible, indicating that this group might represent successful adaptation of
      this clone in the community setting with low antibiotic pressure. The most
      frequently found clone in the MRSA group was spa group C (spa repeat motif,
      DMGGM) and SCCmec type IVA, which represented half of the MRSA isolates and
      corresponded to ST72. ST5-MRSA-II, the most prevalent MRSA clone in Korean
      hospitals, was found in only two isolates. These findings suggest that strains of
      S. aureus nasal carriage in Korean children visiting an outpatient pediatric
      department were different from the strains identified in hospital infections.

PMID- 18346011
TI  - Bone disease after kidney transplantation.
AB  - Post-transplant renal osteopathy (ROP) remains a serious problem, which
      contributes to substantial long-term morbidity of the graft recipients. Bone loss
      is most pronounced during the first months after engraftment; concerning bone
      density development in long-term transplant recipients, controversial data exist.
      The clinical impact of ROP is a marked increase in fracture rate following kidney
      transplantation compared with both general population and patients on dialysis
      treatment. The following review will focus on post-transplant ROP and discuss its
      epidemiology, the clinical features, factors contributing to the pathogenesis of
      this complication, as well as the evaluation, prevention and treatment options
      available for kidney allograft recipients.

PMID- 18346012
TI  - Glucocorticoids reduce pro-inflammatory cytokines and tissue factor in vitro and
      improve function of transplanted human islets in vivo.
AB  - Factors that upregulate the inflammatory status of islets probably contribute to
      detrimental processes leading to islet loss and impaired post-transplant
      function. Glucocorticoids have the potential to counteract inflammation and thus
      improve islet quality and function. However, glucocorticoids have diabetogenic
      properties and are known to hamper islet function in vivo. We examined the effect
      of glucocorticoids on human islets in vitro and in vivo after 48 h of exposure to
      different concentrations of methylprednisolone. Protein and/or mRNA levels of
      insulin, interleukin (IL)-8, macrophage chemoattractant protein (MCP)-1, tissue
      factor (TF), and IL-10 were assessed by enzyme immunosorbent assay and real time
      quantitative reverse transcription-polymerase chain reaction. Viability was
      assessed with fluorescein diacetate-propidium iodide staining, adenosine
      triphosphate (ATP) content and caspase activity. Six-hundred islet equivalents
      (IEQ) were transplanted to severe combined immunodeficiency disease mice and
      graft function assessed by glucose measurements and intraperitoneal glucose
      tolerance tests. Glucocorticoids reduce mRNA and protein levels of TF, MCP-1 and
      IL-8, and enhance ATP content. Insulin secretion was initially inhibited;
      however, after 7 days in culture, it was superior to controls. Islets exposed to
      methylprednisolone cured diabetic mice more effectively than control islets. In
      conclusion, glucocorticoids have potent anti-inflammatory properties on human
      islets without permanent effects on insulin metabolism. Brief glucocorticoid
      exposure improves function of transplanted human islets in vivo.

PMID- 18346013
TI  - CD28 downregulation on CD4+ T cells is associated with age of kidney transplant
      recipient.
AB  - There is a growing body of evidence showing that the intensity of rejection is
      weaker in older kidney allograft recipients while chronic complications, but not
      rejection, are the main causes of graft loss. To investigate whether the age of
      the recipient is a factor affecting the expressions of the CD28, CTLA-4, and
      CD40L costimulatory molecules on CD4+ T cells. Their expression levels were
      determined in 78 kidney transplant recipients aged 17-68 years. The expression
      was assessed on unstimulated and anti-CD3 antibody + IL-2-stimulated CD4+ T
      cells. Median time after transplantation was 20 months and median serum
      creatinine was 1.5 mg/dl. Significant correlations between age and CD28
      expression (r = -0.4, P = 0.0004) on CD4+ T cells and between age and CTLA-4
      expression after stimulation (r = 0.34, P = 0.008) were found. CD40L expression
      on CD4+ T cells was not affected by recipient age. The decreased expression of
      CD28 and enhanced expression of CTLA-4 (after stimulation) associated with age
      may be helpful in transplant acceptance.

PMID- 18346014
TI  - Risk factors for acute, moderate to severe donor reactions associated with
      multicomponent apheresis collections.
AB  - BACKGROUND: Legitimate concerns exist over the safety of donors during
      multicomponent apheresis collections (MACs), when large volumes of red blood
      cells (RBCs) and plasma are removed. This study evaluates the predictive value of
      various donor- and procedure-related variables for moderate to severe donor acute
      adverse events (AAEs). STUDY DESIGN AND METHODS: Data on all apheresis donation
      procedures performed at a large university hospital-based donor center over a 2
      year period were obtained by a review of adverse event forms and procedure logs
      (Trima Accel 5.1, Gambro BCT). Various donor- and procedure-related variables
      were compared between procedures that resulted in moderate to severe AAEs and
      those that did not. RESULTS: Moderate to severe AAEs occurred in 53 (0.47%) of
      11,333 apheresis donation procedures. The majority of events (96.2%) had
      predominantly features of vasovagal reactions (VVRs). Females were at
      significantly higher risk (odds ratio [OR] = 2.8, p < 0.0003) compared to males.
      Donors who experienced AAEs had significantly lower predonation total blood
      volume (TBV) and hematocrit (Hct) and higher total RBC loss and net fluid loss at
      the end of the procedures. Total plasma loss alone was not significantly
      different between the two groups. Total blood loss was significantly higher among
      donors who experienced AAEs as a percentage of the donor's TBV. CONCLUSION:
      Apheresis collections are well tolerated even when multiple components are
      collected, with a very low overall incidence of moderate to severe AAEs (0.47%).
      Small, female donors with lower predonation Hct are at higher risk, especially
      when RBCs are collected.

PMID- 18346015
TI  - Risk factors for hepatitis C virus infection among blood donors in Beijing and
      implications for improving the pretesting donor screening process.
AB  - BACKGROUND: The objective was to determine risk factors of hepatitis C virus
      (HCV) infection in blood donors in Beijing. STUDY DESIGN AND METHODS: A cross
      sectional study was conducted in a total of 112 volunteer blood donors at Beijing
      Red Cross Blood Center (BRCBC) who were identified between January 2002 and
      December 2003 due to isolated HCV antibody reactivity at a donor screening
      procedure. The donors were recalled and interviewed about possible risk factor
      history. Additional blood samples were tested in repeated enzyme immunoassay,
      recombinant immunoblot assay, and nested reverse transcription-polymerase chain
      reaction. Chi-square test, analysis of variance, and multivariate logistic
      regression analysis were conducted to examine associations between HCV serostatus
      and potential risk factors. RESULTS: Among donors identified with isolated HCV
      antibody reactivity at donor screening, the prevalence of confirmed HCV infection
      was 31.3 percent (95% confidence interval [CI], 22.0%-39.2%) and indeterminate
      HCV infection was 22.3 percent (95% CI, 14.7%-30.3%), and the negative prevalence
      was 46.4 percent (95% CI, 37.5%-56.1%). The confirmed HCV cases were more likely
      than the indeterminate HCV cases to have the histories of previous transfusion,
      plasma donation, and hepatitis infection or elevated alanine aminotransferase
      (ALT), whereas the HCV-negative subjects were least likely to have the above
      histories (p < 0.05). CONCLUSION: Histories of blood transfusion before 1995,
      plasma donation, previous hepatitis infection, or elevated ALT were risk factors
      for HCV infection among blood donors in Beijing.

PMID- 18346016
TI  - A comparison of hemolysis and red cell mechanical fragility in blood collected
      with different cell salvage suction devices.
AB  - BACKGROUND: Suction pressure is one variable that can affect the efficiency of
      red blood cell (RBC) recovery for intraoperative autotransfusion. This study
      compared a constant-suction-pressure system with a device that is expected to
      minimize hemolysis by automatically varying the suction pressure. STUDY DESIGN
      AND METHODS: Twenty-two 50-mL reconstituted whole-blood samples were collected
      from a flat surface with either a constant-pressure suction device (BRAT 2
      autologous blood recovery system, COBE Cardiovascular) set to a pressure of -200
      mmHg or a variable-pressure suction device (SmartSuction Harmony surgical suction
      pump, Haemonetics, Inc.). Time of blood collection was recorded and plasma free
      hemoglobin (PFHb) was spectroscopically measured in the aspirated blood.
      Postcollection blood was subjected to RBC mechanical fragility test to
      characterize potential sublethal blood trauma. Relative hemolysis and the mean
      fragility index (MFI) were calculated. RESULTS: Hemolysis was significantly
      reduced with the variable-pressure suction compared to the constant-pressure
      suction (2.17% vs. 3.20%, respectively; p < 0.001). There was no significant
      difference between both suction devices in either the MFI of RBCs (0.632 vs.
      0.673, respectively; p > 0.05) or the collection time at -200 mmHg (54.2 seconds
      vs. 52.8 seconds, respectively; p > 0.05). CONCLUSIONS: Although the variable
      pressure device produced a significant reduction in hemolysis during one-pass
      blood collection, the clinical significance of this reduction is not clear. In
      relative terms, the variable-pressure device would recover an extra 10 mL of RBCs
      for every liter of salvaged RBCs, which is negligible compared to the blood loss
      in major surgery.

PMID- 18346017
TI  - The effect of double- and triple-apheresis platelet product donation on apheresis
      donor platelet and white blood cell counts.
AB  - BACKGROUND: Concerned about the effect of multiple platelet (PLT) product
      donation on donor health, in 2005 the FDA proposed restrictions limiting the
      number of PLT products donated in 12 months. This was based on limited published
      evidence. To provide information on the effect of PLT donation on PLT and
      lymphocyte (LYM) count, hematologic variables were examined in a group of
      multiple PLT product donors. STUDY DESIGN AND METHODS: Donors with at least two
      apheresis PLT donations, one of which was a double- or triple-PLT product, were
      examined. Donor demographics, number of blood donations, and number of apheresis
      PLT products donated were determined. Hematologic variables were evaluated at the
      first and last donation. RESULTS: A total of 471 donors (median age, 48.8 years;
      55% male; median time between first and last donations, 72 weeks) were studied.
      The median number of PLT donations was 4 (range, 1-34) with the median number of
      PLT products donated being 7 (range, 2-65). The median PLT count demonstrated a
      significant increase (14 x 10(9)/L, p = 0.0001) while both white blood cell and
      LYM counts showed significant decreases (-0.2 x 10(9)/L, p = 0.0052; and -0.06 x
      10(9)/L, p = 0.0001, respectively). After adjusting for sex and whole-blood
      donations, LYM count demonstrated a significant decline associated with both
      number of donations (-0.01 x 10(9)/L, p = 0.01) and number of products donated (
      0.005 x 10(9)/L, p = 0.02). PLT count demonstrated a significant increase
      associated with number of products donated (0.42 x 10(9)/L, p = 0.03).
      CONCLUSION: Significant but small LYM decrease and PLT increase were seen.
      Limitations on the number of apheresis PLT products donated within 12 months do
      not seem warranted due to PLT or LYM count changes.

PMID- 18346018
TI  - Improving transfusion safety: implementation of a comprehensive computerized bar
      code-based tracking system for detecting and preventing errors.
AB  - BACKGROUND: To transfuse blood products safely, health care workers must
      accurately identify patients, blood samples, and the blood components. A
      comprehensive bar code-based computerized tracking system was developed and
      implemented to identify and prevent transfusion errors. STUDY DESIGN AND METHODS:
      A data network, wireless devices, and bar-coded labels were pilot tested before
      the system was introduced hospitalwide. The system provided a complete audit
      trail for all transactions. Data from before and after implementation were
      analyzed. RESULTS: Incident reports decreased from a mean of 41.5 reports per
      month in the 6 months before the system was implemented to a mean of 7.2 reports
      per month after implementation. The blood sample rejection rate decreased from
      1.82 percent to a mean of 0.17 percent after implementation. Errors detected by
      the new system were sorted into misscans, skipped steps, wrong steps, and
      prevented identification errors (PIEs). Misscans and skipped steps were the most
      common errors in the first 10 months after implementation. During the final
      transfusion step, PIEs occurred at the rate of about one per month and scans were
      omitted approximately 1 percent of the time. Therefore, it is estimated that
      mistransfusions could occur about once every 100 months on average with the new
      system. CONCLUSIONS: The bar code-based computerized tracking system detected and
      prevented identification and matching errors, thereby reducing the proportion of
      blood samples rejected and increasing patient safety.

PMID- 18346019
TI  - A prospective observational cohort safety study of 5106 platelet transfusions
      with components prepared with photochemical pathogen inactivation treatment.
AB  - BACKGROUND: Inactivation of pathogens and white blood cells in platelet (PLT)
      components with amotosalen and UVA light (INTERCEPT, Cerus Europe BV) has entered
      clinical practice in European blood centers. A prospective cohort study was
      implemented to characterize the safety profile of this new PLT component in a
      broad patient population. STUDY DESIGN AND METHODS: Apheresis or buffy-coat PLT
      components were leukoreduced, suspended in approximately 35 percent plasma and 65
      percent PLT additive solution, and treated with the INTERCEPT process. Blood
      centers were requested to complete a safety data form after each transfusion.
      RESULTS: Data for 5106 INTERCEPT components administered to 651 patients were
      monitored. A total of 5051 (98.9%) transfusions and 609 (93.5%) patients had no
      reported reactions. Fifty-five (1.1%) transfusions were associated with adverse
      events, and 42 (0.8%) were possibly, probably, or related to the PLT transfusion.
      Adverse events occurred in 42 (6.4%) patients, but in only 32 (4.9%) patients was
      a causal relationship to PLT transfusion established. One reaction was serious,
      and no deaths were related to PLT transfusion. Among the transfusions reactions,
      the most frequent clinical events in descending frequency were chills, fever,
      dermatologic reactions, dyspnea, nausea or vomiting, and hypotension. No episodes
      of transfusion-related acute lung injury were reported. CONCLUSIONS: In this
      cohort study, 99.2 percent of transfusions were without reactions attributed to
      PLTs. INTERCEPT PLTs exhibited a safety profile similar to that previously
      reported for conventional PLT components.

PMID- 18346020
TI  - Transfusion and blood donation on the screen.
AB  - BACKGROUND: In the 20th century, blood transfusion has become an indispensable
      therapy in carrying out and improving many medical and surgical applications. Its
      scope of influence goes well beyond that of medicine, because blood donation, an
      action with high social significance, is completely connected to progress in the
      field. STUDY DESIGN AND METHODS: The purpose of this research was to study,
      through films that show transfusion or blood donation, the impression that has
      been given to the public in the course of the 20th century and its sociologic
      impact. To accomplish this, we have used various sources from Histories of Cinema
      and from the Internet to identify films from different countries and from
      different epochs that touch on this theme. RESULTS: With these two components,
      the act of donation and the act of transfusion, the relatively short history of
      blood transfusion is distinguished by upheavals in both the medical and the
      sociopolitical fields of the past century. Movies, the most commonly shared
      cultural event and mirror of society, have simultaneously gone through their
      first century by showing the diversity of our feelings and the human condition.
      CONCLUSION: Through various cinematographic references, the authors offer an
      analysis of the use, by the Seventh Art, of values and illustrations that use
      blood donation and transfusion.

PMID- 18346021
TI  - The role of intravenous iron in anemia management and transfusion avoidance.

PMID- 18346022
TI  - Possible involvement of heparin-binding protein in transfusion-related acute lung
      injury.
AB  - BACKGROUND: In antibody-mediated nonhemolytic transfusion reactions, transfusion
      related acute lung injury (TRALI) tends to occur typically within 2 hours after a
      blood transfusion. White cell antibodies or immune complexes have been frequently
      shown to be associated with the syndrome, although the mechanisms by which they
      induce TRALI are poorly understood. The aim of this study was to characterize
      soluble mediators that are released from cells at an early stage after immune
      stimulation. STUDY DESIGN AND METHODS: To explore the mechanism of TRALI, an in
      vitro whole-blood cell culture assay was established in which cells were
      stimulated by human antibodies and the activation of neutrophils was monitored by
      a cell surface marker (Mac-1) with flow cytometry and by measurement of the
      release of soluble factors, including perforin, interleukin-6, tumor necrosis
      factor-alpha, and heparin-binding protein (HBP) with enzyme-linked immunosorbent
      assays. In addition, the involvement of two neutrophil FcgammaRs (FcgammaRIIIb
      and FcgammaRIIa, also known as CD16 and CD32, respectively) was examined during
      antibody-induced cell activation with anti-FcgammaR blocking antibodies. RESULTS:
      Substantial amounts of HBP were released within 30 minutes of stimulation by
      human antibodies, although other soluble mediators were not released within the
      same period. Furthermore, the release of HBP was mediated via signals through
      both FcgammaRIIIb and FcgammaRIIa. CONCLUSION: HBP appears to be one of the
      primary effector molecules of antibody-mediated nonhemolytic transfusion
      reactions including TRALI.

PMID- 18346023
TI  - Assessment of biofilm-forming ability of coagulase-negative staphylococci
      isolated from contaminated platelet preparations in Canada.
AB  - BACKGROUND: Coagulase-negative staphylococci (CoNS) are the most prevalent
      bacterial contaminants of platelet (PLT) preparations and have been implicated in
      adverse transfusion reactions worldwide. The most frequently identified
      contaminant is Staphylococcus epidermidis, which is noted for its ability to
      maintain chronic hospital-acquired infections by forming biofilms as a chief
      virulence mechanism. STUDY DESIGN AND METHODS: Strains of S. epidermidis isolated
      from contaminated PLT preparations in Canada were distinguished via gene-specific
      polymerase chain reaction (PCR) with divIVA as a marker. Biofilm-forming ability
      was assessed by the presence of the gene icaD, slime production on Congo red
      agar, and biofilm formation on polystyrene surfaces. Production of polysaccharide
      intercellular adhesin (PIA) was resolved by immunofluorescence. RESULTS: Eight of
      the 13 (62%) CoNS isolates under study were identified as S. epidermidis. Of
      these, four strains (50%) were classified as strong biofilm producers. Three of
      the four biofilm-positive strains (75%) produced slime, harbored the icaD gene,
      and had positive expression of PIA. CONCLUSIONS: Despite the presumable commensal
      origin of the CoNS isolates, a large proportion of S. epidermidis strains
      demonstrated a potential for enhanced virulence. Identification of contaminant
      staphylococci as biofilm producers is thus relevant and informative with regard
      to treatment approach in the circumstance of inadvertent infection of a PLT
      recipient.

PMID- 18346024
TI  - The proteome of red cell membranes and vesicles during storage in blood bank
      conditions.
AB  - BACKGROUND: During storage of red cells (RBCs) for transfusion, RBCs undergo a
      number of biochemical and morphologic changes. To be able to identify the
      mechanisms underlying these storage lesions, a proteomic analysis of the
      membranes of RBCs and their vesicles was performed during various periods of
      storage in blood bank conditions. STUDY DESIGN AND METHODS: RBCs and vesicles
      were isolated from RBCs after various storage periods. The proteins of RBC
      membranes and vesicles were separated by gel electrophoresis and identified by a
      semiquantitative proteomic analysis. RESULTS: Our findings confirm previous data,
      such as a storage-associated increase in hemoglobin binding to the membrane and
      aggregation and degradation of the integral membrane protein band 3, suggesting a
      remodeling of the RBC membrane during storage. Our data also show storage
      dependent changes in the membrane association of proteasome and chaperone
      proteins, metabolic enzymes, small G proteins, and signal transduction proteins.
      Vesicles display similar changes in their protein composition during storage.
      CONCLUSION: The results of this analysis indicate that the storage-related
      changes in the RBC membrane are the results of disturbance and/or acceleration of
      physiologic processes such as cellular aging, including vesicle formation. The
      latter may serve to remove damaged membrane patches that would otherwise lead to
      accelerated RBC removal. These data provide a framework for future studies toward
      the development of better storage conditions and a reduction of the side effects
      of RBC transfusion.

PMID- 18346025
TI  - Anti-D and anti-i activities are inseparable in V4-34-encoded monoclonal anti-D:
      the same framework 1 residues are required for both reactivities.
AB  - BACKGROUND: The heavy-chain V4-34 germline gene segment is mandatory for
      pathologic cold-reacting autoantibodies with anti-I/i specificity (cold
      agglutinins) and is also preferentially used by monoclonal immunoglobulin M
      alloantibodies against D and other Rh antigens. The use of the V4-34 segment by
      monoclonal anti-D has previously been shown to also confer anti-I/i reactivity
      (cold agglutinin activity), which has implications for the use of such antibodies
      for Rh blood typing. V4-34 framework 1 (FR1) sequence is believed to be critical
      for cold agglutinin activity of cold agglutinins. STUDY DESIGN AND METHODS: The
      aim of this investigation was to use site-directed mutagenesis of a recombinant
      V4-34-encoded anti-D to determine the contribution of V4-34 FR1 sequence to anti
      D activity and whether mutational modifications in the FR1 region could
      separately alter anti-D and anti-i activities. RESULTS: The results show that
      amino acid changes in V4-34 FR1 at W7, A23, and Y25 have a profound effect on
      anti-D activity as well as on anti-i activity. It was not possible to
      substantially reduce or remove anti-i activity without reducing anti-D activity
      to a comparable extent. CONCLUSIONS: The same nonpolar hydrophobic amino acids in
      FR1 are critical for maintaining both anti-D and anti-i activity. It is proposed
      that these residues influence the conformation of the antigen-binding site.

PMID- 18346026
TI  - International open trial of uniform multi-drug therapy regimen for 6 months for
      all types of leprosy patients: rationale, design and preliminary results.
AB  - OBJECTIVE: To describe the rationale, design and preliminary results of an open
      trial of 6 months uniform multi-drug therapy (U-MDT) for all types of leprosy
      patients assuming a cumulative relapse rate not exceeding 5% over 5 years of
      follow-up. METHODS: We intended to recruit 2500 patients each in multi-bacillary
      (MB) and pauci-bacillary (PB) groups from India (five centres) and China (two
      centres). Standardized clinical criteria were used to assess skin lesions in the
      field. RESULTS: A total of 2912 patients enrolled from November 2003 to May 2007
      (India, 2746; China, 166). MB patients constituted 39% and 3% had grade 2
      disability. During follow-up, 27 patients (0.9%) developed new lesions. Of these,
      78% were on account of reactions. Six patients had clinically confirmed relapse.
      Clofazimine-related skin pigmentation was short-lived and was acceptable to
      patients. We analysed data for clinical status of skin lesions. About 2.9% of
      patients were lost to follow-up; 85.9% completed treatment, of whom 19% had
      inactive skin lesions. PB patients responded better than MB patients (27%vs. 6%;
      P < 0.001). At the end of the first (n = 2013) and second year (n = 807) of
      follow-up post-U-MDT, in 49% and 46% patients, lesions were inactive,
      respectively (59% and 57% in PB, 37% and 28% in MB; P < 0.001). CONCLUSION: U-MDT
      appears to be promising with respect to clinical status of skin lesions.

PMID- 18346027
TI  - Impact of seven rounds of mass administration of diethylcarbamazine and
      ivermectin on prevalence of chronic lymphatic filariasis in south India.
AB  - OBJECTIVE: To evaluate the impact of seven rounds of mass administration of
      diethylcarbamazine (DEC) and ivermectin on the prevalence of chronic lymphatic
      filariasis and to compare it with that observed in a placebo arm in a community
      level trial. METHODS: Cross-sectional clinical surveys were carried out before
      and after seven rounds of mass drug administration (MDA). About 54-75% of the
      target population were treated at each round of MDA. RESULTS: After seven rounds,
      the hydrocele prevalence had declined from the pre-intervention level of 20.5
      5.1% (P < 0.05) in the DEC arm, from 23.9% to 10.4% (P < 0.05) in the ivermectin
      arm and from 20.4% to 10.9% (P < 0.05) in the placebo arm, equivalent to
      reductions of 75.3%, 56.6% and 46.6%, respectively. The lymphoedema/elephantiasis
      prevalence declined only marginally and without statistical significance from
      3.7% to 3.2%, 4.6% to 3.9% and 2.9% to 2.3% in the DEC, ivermectin and placebo
      arm. After the seventh MDA, none of the sampled people in the 0-20 age group was
      found with hydrocele and there was a statistically significant decline in
      hydrocele prevalence in all other age groups in the communities treated with DEC,
      the drug known to have macrofilaricidal effect. The impact was relatively less in
      ivermectin arm. CONCLUSION: Repeated DEC administration has the potential to
      prevent incidence of new hydrocele cases and may resolve the manifestation at
      least in a proportion of affected people. Apart from reducing the microfilaraemia
      prevalence and transmission of infection, MDA also results in significant public
      health benefits by reducing the burden of hydrocele in treated communities.

PMID- 18346028
TI  - High efficacy of two artemisinin-based combinations (artemether-lumefantrine and
      artesunate plus amodiaquine) for acute uncomplicated malaria in Ibadan, Nigeria.
AB  - OBJECTIVE: To test the hypothesis that artesunate plus amodiaquine (ASAQ) is as
      effective as artemether-lumefantrine (AL) in the treatment of acute uncomplicated
      malaria in Nigerian children. METHODS: In an open label, randomized controlled
      clinical trial, children aged 6 months to 10 years were randomized to receive
      artesunate (4 mg/kg daily) plus amodiaquine (10 mg/kg daily) or AL (5-14 kg, one
      tablet; 15-24 kg, two tablets and 25-34 kg, three tablets twice daily). Both drug
      regimens were given for 3 days and follow-up was for 28 days. RESULTS: A total of
      132 children (66 in each group) were randomized to receive either ASAQ or AL. Day
      28 cure rates in the per protocol (PP) population were 93% for ASAQ and 95% for
      AL (OR = 0.71, 95% CI = 0.12-3.99, rho = 0.66). Using Kaplan-Meier product-limit
      estimates of failure, the median survival time for ASAQ was 21 days and for AL 28
      days (P = 0.294). PCR corrected day 28 cure rate for PP populations were 98.4%
      for ASAQ and 100% for AL. Both drugs were well-tolerated. CONCLUSION: ASAQ is as
      effective as AL and both combinations were efficacious and safe.

PMID- 18346029
TI  - The unbearable lightness of technocratic efforts at dengue control.
AB  - OBJECTIVE: To identify key elements that should provide an added value and assure
      sustainable effects of the deployment of technical tools for Aedes aegypti
      control. METHODS: An observational study was conducted between April 2001 and
      March 2002 in 30 blocks (1574 houses) in the central zone of Guantanamo city. A
      trial that combined two complementary technical interventions, the distribution
      of new ground level water tanks and the intensive use of insecticide, was nested
      in May 2001. Another 30 blocks (1535 houses) were selected as control area. We
      assessed community perceptions and household risk behaviour at baseline and after
      9 months, and measured the trial's impact through entomological indices. RESULTS:
      Perceived self efficacy to solve A. aegypti infestation and prevent dengue was
      not modified. We found no changes in behaviour. In the study area the container
      indices decreased significantly from 0.7% before to 0.1% 1 month after the
      intervention. Six months later, they had increased to 2.7% and uncovered new
      water tanks constituted 75.9% of all breeding sites. Over the 9 months after the
      trial the average monthly house indices were similar in the study and control
      areas. A technical approach and lack of community involvement in the trial's
      implementation were the main causes of these short-lived results. CONCLUSIONS:
      Top-down deployment of technical tools without active involvement of the
      community has a temporary effect and does not lead to the behavioural changes
      necessary for sustainable A. aegypti control.

PMID- 18346030
TI  - Debating the quality and performance of health systems at a global level is not
      enough, national debates are essential for progress.

PMID- 18346031
TI  - Identification of a novel HLA-B allele, HLA-B*5529, by haplotype-specific
      sequencing.
AB  - We have identified a novel HLA-B allele, B*5529. The novel allele differs from
      HLA-B*5501 by a single nucleotide substitution at codon 479 in exon 3 resulting
      in an amino acid change from alanine to valine. This alteration neither affects
      the peptide binding site nor the T-cell receptor (TCR) contact residues. Thus,
      the newly found allele is estimated to have a low alloreactive potential in case
      of a mismatch to the most common HLA-B allele B*5501.

PMID- 18346032
TI  - Description of two new major histocompatibility complex (MHC) class II DRB1 [Pan
      troglodytes (Patr)-DRB1] alleles.
AB  - Sequence-based typing strategy is used to identify polymorphism of Patr-DRB1. Two
      new Patr-DRB1 are described.

PMID- 18346033
TI  - Identification of a novel HLA-B*54 allele, B*5411, by sequence-based typing in a
      Chinese individual.
AB  - We report here a novel human leukocyte antigen (HLA)-B*5411 allele identified by
      sequence-based typing in a Chinese individual. The novel B*5411 is identical to
      B*5404, with the exception of four base substitutions at position 120 (A>C), 134
      (G>C), 143 (C>G), and 156 (A>T) of exon 3 resulting in codon no. 131, changed
      from AGC (Ser) to CGC (Arg), and codon no. 143, changed from ACC (Thr) to TCC
      (Ser).

PMID- 18346034
TI  - Identification of a novel HLA-G allele, HLA-G*010113, in a Korean individual.
AB  - In the present study, a novel human leucocyte antigen-G allele, G*010113, was
      identified via direct sequencing from donor gDNA in a Korean population. This
      allele differs from G*01010201 by a single nucleotide substitution, C to T, in
      codon 169 of exon 3 but did not result in any amino acid change.

PMID- 18346035
TI  - Exercise and the pediatric heart transplant recipient: a good thing or a bad
      idea?

PMID- 18346036
TI  - Lung transplantation in a patient with a thrombophilic disorder.
AB  - The prothrombin G20210A mutation has been associated with an increased risk of
      graft failure in renal transplant recipients. Little is known about the potential
      effect of this mutation on lung transplant recipients. We report the case of
      bilateral lung transplantation in a patient with cystic fibrosis who was
      heterozygous for the G20210A mutation of the prothrombin gene.

PMID- 18346037
TI  - Are children after liver transplant more prone to non-alcoholic fatty liver
      disease?

PMID- 18346038
TI  - T-cell post-transplantation lymphoproliferative disorder, a rare and challenging
      late complication of solid organ transplantation.

PMID- 18346039
TI  - Post-transplant lymphoproliferative disorder after pediatric liver
      transplantation: characteristics and outcome.
AB  - Post-Transplant Lymphoproliferative Disorder (PTLD) is a life threatening
      complication in organ transplant recipients. Risk factors include primary Epstein
      Barr virus infection, intensity of immunosupression and cytomegalovirus
      infection. OBJECTIVES: To evaluate the incidence, clinical presentation, risk
      factors, histopathologic appearance and outcome of pediatric liver recipients
      with PTLD at our institution. METHOD: Retrospective, descriptive and
      observational analysis. Between November 1992 and December 2005, 383 liver
      transplants were performed. The diagnosis of PTLD was based on clinical history
      and physical examination and confirmed by histologic appearance and
      immunohistologic staining. Knowles' classification was used for histopathologic
      diagnosis. RESULTS: The incidence of PTLD was 5.7% (n: 22p). The average onset
      after tansplantation (OLT) was 24.9 months. Clinical manifestations were malaise,
      anorexia, fever of more than 3 days, peripheral adenopathy, tonsillar
      hypertrophy, abdominal mass, hepatosplenomegaly, snoring, interstitial pulmonary
      infiltrate, G.T.-tract bleeding, rash, submaxilar mass. Histopathologic diagnosis
      were Plasmocytic Hyperplasia (n: 10), Polymorphic Lymphoproliferative Disorder
      (n: 8), Non-Hodgkin Lymphoma (n: 4). Mortality was 18%. CONCLUSION: The clinical
      presentations were protean and not specific. A high index of suspicion is
      important for early diagnosis as it correlates with more benign lesions and more
      favorable outcume. The lower mortality rate in our series is concordant with that
      reported in more recent articles.

PMID- 18346040
TI  - Saviors as saints or sinners?

PMID- 18346041
TI  - Preliminary evidence that morning vaccination is associated with an enhanced
      antibody response in men.
AB  - Variation in response to vaccination, particularly in vulnerable groups, provides
      a strong rationale for developing vaccine adjuvants. If there were consistent
      diurnal variation in immune response, this could inform a simple intervention for
      enhancing vaccine efficacy. Data from two studies are presented examining morning
      versus afternoon vaccine administration; in the first, hepatitis A vaccine was
      administered to young adults, and in the second, influenza vaccine to older
      community-based adults. Men, but not women, vaccinated in the morning mounted a
      better peak antibody response to both hepatitis A and the A/Panama influenza
      strain. These results indicate that it would be worthwhile testing this effect in
      a large randomized control trial with vaccination during time periods
      representing the extremes of hormonal and cytokine diurnal rhythms.

PMID- 18346042
TI  - P300 amplitude age reductions are not caused by latency jitter.
AB  - Studies of the event-related potentials (ERPs) P3a/P3b have given insights into
      age effects on cognitive processes in the brain, and it has been established that
      latency increases and amplitude decreases with age. However, if latency jitter,
      that is, variation in single trial latencies, is larger in elderly than in
      younger participants, this may create an artificial age-amplitude correlation.
      The aim of this article is to test whether correction for latency jitter affects
      the P3a/P3b age correlations. One hundred thirty-three healthy adults (20-88
      years old) went through a 3-stimuli visual oddball paradigm. Latency jitter was
      corrected by use of a Maximum Likelihood Estimation method. The results showed
      that corrections for latency jitter did not significantly affect the correlations
      between P3a/P3b and age. It is concluded that previous reports of amplitude
      reduction as a function of age seem to be valid regardless of whether latency
      jitter correction has been applied.

PMID- 18346043
TI  - Cognitive control after distraction: event-related brain potentials (ERPs)
      dissociate between different processes of attentional allocation.
AB  - Attentional reallocation after a distracting event is an important function of
      cognitive control. This process is tapped by the reorienting negativity (RON)
      event-related brain potential. It was argued that the RON reflects orientation of
      attention to relevant information in working memory. To test this hypothesis
      participants performed an auditory duration discrimination task. The stimuli were
      presented in a frequent standard or a rare deviant pitch with deviants resulting
      in behavioral distraction. Participants accomplished this task under two
      conditions: In the refocus condition participants were asked to respond to every
      stimulus; in the reorient condition participants were instructed to ignore
      deviant stimuli and omit a reaction. The results suggest that different functions
      of attentional allocation are reflected by two RON subcomponents: the fast
      orientation of the focus of attention in working memory and a subsequent
      poststimulus evaluation process.

PMID- 18346044
TI  - Norsolorinic acid from Aspergillus nidulans inhibits the proliferation of human
      breast adenocarcinoma MCF-7 cells via Fas-mediated pathway.
AB  - Norsolorinic acid, isolated from the Aspergillus nidulans, was investigated for
      its antiproliferative activity in human breast adenocarcinoma MCF-7 cells. To
      identity the anticancer mechanism of norsolorinic acid, we assayed its effect on
      apoptosis, cell cycle distribution, and levels of p53, p21/WAF1, Fas/APO-1
      receptor and Fas ligand. The results showed that norsolorinic acid induced
      apoptosis of MCF-7 cells without mediation of p53 and p21/WAF1. We suggest that
      Fas/Fas ligand apoptotic system is the main pathway of norsolorinic acid-mediated
      apoptosis of MCF-7 cells. Our study reports here for the first time that the
      activity of the Fas/Fas ligand apoptotic system may participate in the
      antiproliferative activity of norsolorinic acid in MCF-7 cells.

PMID- 18346045
TI  - Inhibitory effects on cytochrome p450 enzymes of pentamidine and its amidoxime
      pro-drug.
AB  - Pentamidine is an antimicrobial drug, intravenously used in the treatment of
      trypanosomiasis, leishmaniasis or pneumocystis pneumonia. To elucidate potential
      drug interactions with pentamidine and N,N'-dihydroxypentamidine, respectively,
      the cytochrome P450 (CYP450) inhibitory properties of these compounds were
      determined. The study was performed in vitro by using human liver microsomes and
      marker substrates of several CYP450 isoenzymes. Marker activities were
      investigated by high-performance liquid chromatography in presence of known
      selective inhibitors or at different concentrations of pentamidine and N,N'
      dihydroxypentamidine, respectively. No or only minor influence on CYP1A2, 2A6,
      2C9, 2C19, 2D6, 2E1 and 3A4 marker activities could be observed, suggesting that
      neither of the tested substances would exert a significant effect on hepatic
      CYP450 isoenzymes responsible for the metabolism of co-administrated drugs in
      vivo. However, in vivo studies are needed before final conclusions can be drawn.

PMID- 18346046
TI  - Pharmacologic effects of ospemifene in rhesus macaques: a pilot study.
AB  - Ospemifene (Ophena) is a new selective oestrogen receptor modulator currently in
      phase III clinical development for treatment of post-menopausal vulvar and
      vaginal atrophy. In the present study, we examined the pharmacokinetics,
      toxicity, and DNA adduct forming potential of ospemifene in the liver and
      endometrium of rhesus macaques following single and subchronic dosing schedules
      to better understand the potential toxicologic effects of ospemifene. During
      single weekly dosing, six macaques were administered 35 mg/kg/week ospemifene
      orally for 3 weeks. Pharmacokinetics, haematologic toxicity, uterotrophic effects
      and serum cholesterol levels were monitored. Additionally, two animals were
      subchronically dosed with 60 mg ospemifene for 9 weeks, followed by 12 mg/day for
      3 weeks. Serum cholesterol and pharmacokinetics were monitored, and serial liver
      and endometrial biopsies were collected during and after treatment to evaluate
      DNA adduct formation. Following single weekly dosing, no significant haematologic
      toxicities or uterotrophic effects associated with ospemifene were observed. Peak
      absorption was 4-5 hr, and the elimination half-life was approximately 22 hr.
      Serum low-density lipoprotein and triglyceride levels trended lower while no
      other effects on serum lipids were observed. Subchronic dosing resulted in no
      haematologic toxicity, a lowering of low-density lipoprotein and triglyceride
      levels, and an increase in high-density lipoprotein levels that were reversed
      following cessation of dosing. No clinically relevant uterine or endometrial
      effects were observed, and no DNA adducts were detected in the liver or
      endometrial biopsies. The results of our pilot study show that ospemifene may
      lack genotoxic and toxic effects while having a favourable pharmacokinetic
      profile.

PMID- 18346047
TI  - The prescribing pattern of a new antipsychotic: a descriptive study of
      aripiprazole for psychiatric in-patients.
AB  - In June 2004, aripiprazole was marketed as a second-generation antipsychotic with
      an entire new mechanism of action. The objective of this descriptive study is to
      examine the day-to-day prescriptions of aripiprazole to an unselected population
      of psychiatric in-patients. From 1 February to 1 May 2006, present and former in
      patients treated with aripiprazole were identified. Prescriptions of aripiprazole
      and psychoactive comedication were collected retrospectively from the patient
      records. Seventy-one patients, mainly schizophrenic, received aripiprazole 2.5 to
      55 mg/day for median 350 days. The median average exposure was 18.9 mg/day (range
      2.5-45 mg/day) and exceeded 15 and 30 mg/day in 63% and 4.2% of the patients,
      respectively. Generally, aripiprazole was either added to the existing
      antipsychotic treatment or replaced other antipsychotics; only 17% of the
      patients were treatment-naive. In 25% aripiprazole, monotherapy was commenced
      whereas aripiprazole-antipsychotic combinations were initially prescribed in 75%.
      Overall, 85% of the patients received periods of antipsychotic polypharmacy and
      aripiprazole was combined with 17 different antipsychotics. Each patient received
      median three (range 0-8) psychoactive drugs parallel with aripiprazole. This
      study demonstrates reality in psychopharmacology and quote aripiprazole as
      example. In day-to-day practice, aripiprazole is used as part of highly
      individualized regimens comprising polypharmacy and excessive dosing. Although
      theoretically appropriate for some patients, this approach also implies
      conducting unblinded and uncontrolled mini-experiments. Sparse evidence supports
      this practice and effectiveness studies of aripiprazole that takes into account
      the true complexity of clinical prescribing are urgently needed.

PMID- 18346048
TI  - Theaflavin-3-gallate and theaflavin-3'-gallate, polyphenols in black tea with
      prooxidant properties.
AB  - This study compared the in vitro responses of human gingival fibroblasts and of
      carcinoma cells derived from the tongue to theaflavin-3-gallate (TF-2A) and
      theaflavin-3'-gallate (TF-2B), polyphenols in black tea. The antiproliferative
      and cytotoxic effects of the theaflavin monomers were more pronounced to the
      carcinoma, than to the normal, cells. In phosphate buffer at pH 7.4, the
      theaflavins generated hydrogen peroxide and the superoxide anion, suggesting that
      their mode of toxicity may be due, in part, to the induction of oxidative stress.
      In a cell-free assay, TF-2A and TF-2B reacted directly with reduced glutathione
      (GSH), in a time- and concentration-dependent manner. Intracellular storages of
      GSH were depleted on treatment of the cells with the theaflavin monomers.
      Depletion of intracellular GSH was more extensive with TF-2A than with TF-2B and
      was more pronounced in the carcinoma, than in the normal, cells. The toxicities
      of the theaflavins were potentiated when the cells were cotreated with the GSH
      depleter, d,l-buthionine-[S,R]-sulfoximine. In the presence of catalase, pyruvate
      and divalent cobalt, all scavengers of reactive oxygen species, the
      cytotoxicities of the theaflavins were lessened. TF-2A and TF-2B induced lipid
      peroxidation in the carcinoma cells, whereas in the fibroblasts, peroxidation was
      evident upon exposure to TF-2A, but not to TF-2B. These studies demonstrated that
      the black tea theaflavin monomers, TF-2A and TF-2B, act as prooxidants and induce
      oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.

PMID- 18346049
TI  - Caffeine inhibits the proliferation of liver cancer cells and activates the
      MEK/ERK/EGFR signalling pathway.
AB  - Caffeine has been reported to prevent hepatocarcinogenesis. We investigated the
      molecular mechanisms by which caffeine inhibits the growth of hepatocellular
      carcinoma (HCC) cells. We found that caffeine inhibited the proliferation of HCC
      cells via cell cycle arrest independent of apoptosis. We revealed a novel
      signalling axis for caffeine involving activation of the mitogen-activated ERK
      regulating kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway that
      resulted in the downstream up-regulation of epidermal growth factor receptor
      (EGFR), although the MEK/ERK/EGFR signalling pathway was not involved in the
      growth inhibitory effect of caffeine. Our data reveal that caffeine could be a
      promising candidate for the treatment of patients with HCC.

PMID- 18346050
TI  - Atomoxetine increases histamine release and improves learning deficits in an
      animal model of attention-deficit hyperactivity disorder: the spontaneously
      hypertensive rat.
AB  - Substantial development in the pharmacological treatment for attention-deficit
      hyperactivity disorder (ADHD) has been made recently including approval of new
      non-stimulant agents targeting noradrenergic, histaminergic and dopaminergic
      systems. Among such, atomoxetine has been widely used, although its mechanism of
      action is poorly understood. It is known that central nervous system histamine is
      closely associated with cognition and it was recently shown that both atomoxetine
      and methylphenidate enhance cortical histamine release in rats. To that end, the
      aim of our study was to investigate the effect of atomoxetine (2 mg/kg,
      intraperitoneally) on histamine release using the microdialysis technique in the
      spontaneously hypertensive rat (SHR), a suitable genetic model for ADHD. Our data
      confirmed that atomoxetine increases extracellular levels of histamine in the
      prefrontal cortex, a brain region that is implicated in the pathophysiology of
      ADHD. Given the tie between histamine neurotransmission and treatment of
      cognitive dysfunction, we also assessed the effects of atomoxetine on learning
      and memory as measured by the Morris water maze in SHR. The results indicated
      that atomoxetine significantly ameliorated performance in the Morris water maze,
      consistent with its histamine-enhancing profile. In conclusion, the current study
      provides further support for the notion that the therapeutic effect of
      atomoxetine could involve activation of histamine neurotransmission within the
      prefrontal cortex.

PMID- 18346051
TI  - Antitumoural effect of an L-amino acid oxidase isolated from Bothrops jararaca
      snake venom.
AB  - An L-amino acid oxidase (BjarLAAO-I) from Bothrops jararaca snake venom was
      highly purified using a stepwise sequential chromatography on Sephadex G-75,
      Benzamidine Sepharose and Phenyl Sepharose. Purified BjarLAAO-I showed a
      molecular weight around 60,000 under reducing conditions and about 125,000 in the
      native form, when analysed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and gel filtration, respectively. BjarLAAO-I is a homodimeric
      acidic glycoprotein, pI approximately 5.0, and N-terminal sequence showing close
      structural homology with other snake venom LAAOs. The purified enzyme catalysed
      the oxidative deamination of L-amino acids, the most specific substrate being L
      Phe. Five amino acids, L-Ser, L-Pro, L-Gly, L-Thr and L-Cys were not oxidized,
      clearly indicating a significant specificity. BjarLAAO-I significantly inhibited
      Ehrlich ascites tumour growth and induced an influx of polymorphonuclear cells,
      as well as spontaneous liberation of H(2)O(2) from peritoneal macrophages. Later,
      BjarLAAO-I induced mononuclear influx and peritoneal macrophage spreading.
      Animals treated with BjarLAAO-I showed higher survival time.

PMID- 18346052
TI  - Deficiency in cytosolic malic enzyme does not increase acetaminophen-induced
      hepato-toxicity.
AB  - Cytosolic malic enzyme (ME-1) is a nicotinamide adenine dinucleotide phosphate
      (NADP)-dependent enzyme that generates NADPH. The activity of this enzyme, the
      reversible oxidative decarboxylation of malate to yield pyruvate, links
      glycolytic pathway to citric acid cycle. The high level of ME-1 expression in
      liver, and its involvement in NADPH production, suggests reduced ME-1 activity
      might compromise hepatic production of reduced glutathione (GSH) by the NADPH
      dependent enzyme glutathione reductase, and hence affect xenobiotic
      detoxification. The role of ME-1 in liver detoxification was evaluated in Mod1
      deficient mice (mod1(-/-)) by evaluating their sensitivity to acetaminophen
      induced liver injury. The results show that mod1(-/-) mice are not more sensitive
      to acetaminophen hepato-toxicity. Although GSH levels were initially depleted
      more in the mod1(-/-) liver than in wild-type controls, the GSH levels recovered
      quickly. In conclusion, our data indicate that ME-1 deficiency does not adversely
      affect GSH-dependent detoxification.

PMID- 18346053
TI  - Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent
      diabetes mellitus rats.
AB  - We investigated the effect of an aqueous extract of Withania somnifera (WS) on
      insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats.
      NIDDM was induced by single intraperitoneal injection of streptozotocin (100
      mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally
      once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days
      after streptozotocin injection). A group of citrate control rats (group I) were
      also maintained that has received citrate buffer on the second day of their
      birth. A significant increase in blood glucose, glycosylated haemoglobin
      (HbA(1)c) and serum insulin levels were observed in NIDDM control rats. Treatment
      with WS reduced the elevated levels of blood glucose, HbA(1)c and insulin in the
      NIDDM rats. An oral glucose tolerance test was also performed in the same groups,
      in which we found a significant improvement in glucose tolerance in the rats
      treated with WS. The insulin sensitivity was assessed for both peripheral insulin
      resistance and hepatic insulin resistance. WS treatment significantly improved
      insulin sensitivity index (K(ITT)) that was significantly decreased in NIDDM
      control rats. There was significant rise in homeostasis model assessment of
      insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment
      significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data
      suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by
      improving insulin sensitivity.

PMID- 18346054
TI  - Insulin-secretagogue activity of p-methoxycinnamic acid in rats, perfused rat
      pancreas and pancreatic beta-cell line.
AB  - This study investigated the effect of p-methoxycinnamic acid (p-MCA) on plasma
      glucose and insulin concentrations in normal and streptozotocin-induced diabetic
      rats. In both fasting and glucose-loading conditions, an oral administration of p
      MCA (40-100 mg/kg) significantly decreased plasma glucose and also increased
      plasma insulin concentrations in both normal and diabetic rats. The onset of the
      p-MCA-induced antihyperglycaemia/hypoglycaemia was observed at 1 hr after
      administration. In perfused rat pancreas, p-MCA (10-100 microM) stimulated
      insulin secretion about 1.4- and 3.1-fold of basal-control group. In addition, p
      MCA (10 microM) enhanced glucose-induced insulin secretion. Moreover, p-MCA
      stimulated insulin secretion and increased intracellular Ca(2+) concentration
      ([Ca(2+)](i)) in insulinoma-1 cells. Taken together, our findings suggested that
      p-MCA exerted antihyperglycaemic/hypoglycaemic effect by stimulating insulin
      secretion from pancreas and could be developed into a new potential for
      therapeutic agent used in type 2 diabetic patients.

PMID- 18346055
TI  - Arsenic trioxide-induced apoptosis in H9c2 cardiomyocytes: implications in
      cardiotoxicity.
AB  - Arsenic trioxide (As(2)O(3)) achieved dramatic remissions in patients with acute
      promyelocytic leukaemia. Clinical reports have shown that treatment was
      associated with cardiotoxicity. We investigated the toxic mechanisms of As(2)O(3)
      in H9c2 cardiomyocytes. Clinically relevant concentrations of As(2)O(3) (2-10
      microM) reduced the viability of H9c2 cells in a concentration-dependent manner.
      The decreased cell viability was because As(2)O(3) induced cell apoptosis (cell
      shrinkage, nuclear alterations and caspase-3 activation), or even necrosis at
      higher concentrations. Inhibition of caspase-3 with a specific inhibitor, Ac-DEVD
      CHO, suppressed apoptosis induced by As(2)O(3). In addition, reactive oxygen
      species formation and cellular Ca(2+) overload were observed in H9c2 cells
      exposed to As(2)O(3), which was partly inhibited by vitamin E and verapamil.
      These results suggest that As(2)O(3)-induced cardiotoxicity is mediated, at least
      in part, by activation of caspase-3 pathway, which may be triggered by reactive
      oxygen species formation and intracellular Ca(2+) overload.

PMID- 18346056
TI  - Self-management strategies to reduce pain and improve function among older adults
      in community settings: a review of the evidence.
AB  - CONTEXT: Self-management strategies for pain hold substantial promise as a means
      of reducing pain and improving function among older adults with chronic pain, but
      their use in this age group has not been well defined. OBJECTIVE: To review the
      evidence regarding self-management interventions for pain due to musculoskeletal
      disorders among older adults. DESIGN: We searched the Medline and Cumulative
      Index to Nursing and Allied Health Literature databases to identify relevant
      articles for review and analyzed English-language articles that presented outcome
      data on pain, function, and/or other relevant endpoints and evaluated
      programs/strategies that could be feasibly implemented in the community.
      Abstracted information included study sample characteristics, estimates of
      treatment effect, and other relevant outcomes when present. RESULTS: Retained
      articles (N = 27) included those that evaluated programs sponsored by the
      Arthritis Foundation and other programs/strategies including yoga, massage
      therapy, Tai Chi, and music therapy. Positive outcomes were found in 96% of the
      studies. Proportionate change in pain scores ranged from an increase of 18% to a
      reduction of 85% (median = 23% reduction), whereas change in disability scores
      ranged from an increase of 2% to a reduction of 70% (median = 19% reduction).
      Generalizability issues identified included limited enrollment of ethnic minority
      elders, as well as non-ethnic elders aged 80 and above. CONCLUSIONS: Our results
      suggest that a broad range of self-management programs may provide benefits for
      older adults with chronic pain. Research is needed to establish the efficacy of
      the programs in diverse age and ethnic groups of older adults and identify
      strategies that maximize program reach, retention, and methods to ensure
      continued use of the strategies over time.

PMID- 18346057
TI  - Influence of prescription benefits on reported pain in cancer patients.
AB  - OBJECTIVE: To identify associations between prescription coverage and cancer pain
      and its sequelae in indigent patients. DESIGN AND SETTING: A retrospective chart
      review at UMDNJ-University Hospital. PATIENTS AND OUTCOME MEASURES: Charts from
      20 patients with Medicaid and 20 patients categorized as Self-pay/Charity Care
      were analyzed for the influence of insurance coverage on reported pain at the
      time of a hospital discharge and at three subsequent clinic visits. Patient and
      disease characteristics, pain regimens, doses, reported pain and its impact were
      determined. RESULTS: The groups were statistically indistinguishable except for
      age and ethnicity. The Medicaid group was younger and had a majority of African
      Americans while the Self-pay/Charity Care patients had a majority of Hispanics.
      Lower doses of transdermal fentanyl were prescribed to Self-pay/Charity Care
      patients. Self-pay/Charity Care patients tended to report higher pain levels, but
      this was statistically significant only at the second clinic visit. The clinical
      significance of differences in pain intensity was reflected in differences in
      unscheduled visits and admissions. Adherence to pain regimens improved in the
      Medicaid group and diminished in the Self-pay/Charity Care group, but the
      differences did not achieve statistical significance. Lack of funds as the reason
      for non-adherence was only given by Self-pay/Charity Care patients. CONCLUSION:
      Indigent patients without prescription coverage trended toward reporting more
      cancer pain, received lower doses of transdermal fentanyl, and trended to lower
      adherence to pain regimens due to financial reasons. The trends observed in this
      pilot study will guide the design of a hypothesis-driven regression analysis.

PMID- 18346058
TI  - Prevalence of chronic pain in a representative sample in the United States.
AB  - OBJECTIVE: Chronic pain is a common reason for seeking medical care. We estimated
      the prevalence of chronic regional and widespread pain in the United States
      population overall, and by age, sex, and race/ethnicity. SETTING: We examined the
      data from 10,291 respondents who participated in the 1999-2002 NHANES (National
      Health and Nutrition Examination Survey) and completed a pain questionnaire.
      Items allowed classification of chronic (>or=3 months) pain as regional or
      widespread. We used regression models to test the association of sex and
      race/ethnicity with each pain outcome, adjusting for age. RESULTS: Chronic pain
      prevalence estimates were 10.1% for back pain, 7.1% for pain in the legs/feet,
      4.1% for pain in the arms/hands, and 3.5% for headache. Chronic regional and
      widespread pain were reported by 11.0% and 3.6% of respondents, respectively.
      Women had higher odds than men for headache, abdominal pain, and chronic
      widespread pain. Mexican-Americans had lower odds compared with non-Hispanic
      whites and blacks for chronic back pain, legs/feet pain, arms/hands pain, and
      regional and widespread pain. CONCLUSION: The population prevalence of chronic
      pain in the United States was lower than previously reported, with smaller sex
      related differences and some variation by race/ethnicity.

PMID- 18346059
TI  - Oral ketamine for pain relief in a child with abdominal malignancy.
AB  - Oral ketamine has been found to be effective during invasive procedures in
      children with malignancy. To the best of our knowledge, analgesic effects of oral
      ketamine have not been reported in pediatric cancer pain management. We described
      a patient with end-stage cancer pain that was resistant to opioids and was
      relieved by oral ketamine.

PMID- 18346060
TI  - Pregabalin in the treatment of refractory neuropathic pain: results of a 15-month
      open-label trial.
AB  - OBJECTIVE: Neuropathic pain associated with postherpetic neuralgia (PHN) and
      painful diabetic peripheral neuropathy (DPN) can be intractable and may not
      respond to commonly used treatments, such as tricyclic antidepressants (TCAs) and
      opioids. This long-term, open-label study was a preliminary evaluation of
      pregabalin for patients whose pain had been judged refractory to other treatments
      for neuropathic pain. DESIGN: Patients had previously participated in double
      blind, placebo-controlled, randomized trials of pregabalin in DPN and PHN. They
      had moderate to severe neuropathic pain despite treatment with gabapentin, a TCA,
      and a third medication (e.g., other anticonvulsants, opioid, selective serotonin
      reuptake inhibitor, tramadol). Flexible-dosage pregabalin 150-600 mg/day was
      taken for 3-month periods followed by 3- to 28-day pregabalin "drug holidays,"
      with an analysis up to 15 months (five treatment cycles). Pain intensity was
      measured using the visual analog scale of the Short-Form McGill Pain
      Questionnaire. RESULTS: In total, 81 patients were included in this analysis.
      Pregabalin 150-600 mg/day was associated with clinically meaningful and sustained
      pain reduction during each treatment cycle. During pregabalin "drug holidays,"
      pain quickly returned to baseline levels; it was reduced again when pregabalin
      was reinstated. CONCLUSIONS: These results suggest that pregabalin may be
      beneficial in patients with neuropathic pain who have had an unsatisfactory
      response to treatment with other medications.

PMID- 18346061
TI  - Using evidence in pain practice: Part II: Interpreting and applying systematic
      reviews and clinical practice guidelines.
AB  - Systematic reviews and clinical practice guidelines are useful tools for bringing
      evidence into pain practice. However, even when their conclusions or
      recommendations appear valid, interpreting and applying systematic reviews and
      clinical practice guidelines in everyday practice is not always straightforward.
      Judging external validity or applicability of findings requires careful
      consideration of factors related to patient selection, clinical setting,
      feasibility, costs, and availability of interventions. Clinicians should also
      consider whether effects on clinically relevant outcomes are large enough to
      warrant use of the intervention in question. Other challenges to using systematic
      reviews and clinical practice guidelines in pain practice include the need to
      make decisions about pain interventions when evidence is weak or inconclusive,
      and the increasing and confusing presence of discordant systematic reviews and
      clinical practice guidelines. This article discusses how to evaluate
      applicability and clinical relevance of systematic reviews and clinical practice
      guidelines, and provides a framework for approaching clinical decisions when
      evidence is weak or conflicting.

PMID- 18346062
TI  - Using evidence in pain practice: Part I: Assessing quality of systematic reviews
      and clinical practice guidelines.
AB  - The best evidence should inform all clinical decisions, but physicians cannot
      realistically keep up with all of the literature. Two types of preprocessed
      evidence that can help busy clinicians incorporate evidence into everyday medical
      decision-making are systematic reviews and clinical practice guidelines. However,
      conclusions of systematic reviews and recommendations of evidence-based clinical
      practice guidelines should not be accepted at face value. Like primary studies,
      they must adhere to rigorous standards in order to reduce error and bias. In
      fact, low-quality systematic reviews and guidelines can be very misleading. This
      article discusses what factors distinguish a high-quality systematic review. It
      also examines the difference between systematic reviews and clinical practice
      guidelines, and what factors distinguish a high-quality guideline. A separate
      article discusses how to interpret and apply systematic reviews and clinical
      practice guidelines, particularly when evidence is weak or inconclusive, or when
      different systematic reviews or guidelines are discordant.

PMID- 18346063
TI  - Reduction of topical anesthetic onset time using ultrasound: a randomized
      controlled trial prior to venipuncture in young children.
AB  - BACKGROUND: Ultrasound treatment prior to topical anesthetic application has been
      shown to speed anesthesia onset by enhancing anesthetic penetration into the
      skin. OBJECTIVE: To evaluate a low-frequency ultrasound device to facilitate
      absorption of topical anesthetic in young children who require venipuncture.
      METHODS: This was a prospective controlled comparison of analgesic effect of a 5
      minute application of liposomal lidocaine cream after ultrasound treatment, with
      a 30-minute application of liposomal lidocaine cream, in children aged 3 to 7
      years undergoing venipuncture. Children rated the pain of the venipuncture using
      the Wong-Baker FACES Pain Rating Scale (FACES) (0 = no pain, 10 = maximal pain),
      and parents rated their child's pain using a 100-mm (0 = no pain, 100 = maximal
      pain) visual analogue scale (VAS). Venipuncture skin sites were evaluated for
      effect immediately posttreatment, and at 24 to 72 hours post phlebotomy. RESULTS:
      Seventy subjects were enrolled: the first 10 patients comprised a pilot series,
      receiving the ultrasonic treatment and liposomal lidocaine cream; the next 60
      subjects were randomized, including 29 allocated to the ultrasound treatment
      group, and 31 randomized to the 30-minute control treatment with liposomal
      lidocaine cream. Demographics were similar between the two groups. Mean child's
      FACES scale results were similar: Ultrasound group 4.78 (95% CI; 3.06, 6.52),
      CONTROL group 4.32 (95% CI; 2.82, 5.82) (P = 0.72); and mean parent VAS scores
      were also the same: Ultrasound: 19.1 (95% CI; 10.3, 27.8), CONTROL: 23.2 (95% CI;
      14.7, 31.7) (P = 0.87). Skin effects immediately after ultrasound were limited to
      minor redness in 9/39 children and significant redness in 2/29 patients.
      CONCLUSION: Ultrasound treatment speeds time of onset of liposomal lidocaine
      cream anesthesia in young children undergoing venipuncture. Side effects were
      mild in our population.

PMID- 18346064
TI  - Prevalence and characteristics of chronic pain in patients admitted to an
      outpatient drug and alcohol treatment program.
AB  - OBJECTIVES: To evaluate the prevalence, characteristics, and correlates of
      chronic pain in a population of predominantly employed, alcoholic patients
      attending an outpatient drug and alcohol treatment program. METHODS: A pain
      survey was administered to 79 patients attending an outpatient drug and alcohol
      treatment program situated in a suburban community outside of New York City.
      Chronic severe pain was defined as pain that 1) had persisted for at least 6
      months; and 2) was either moderate to severe in intensity or significantly
      interfered with daily activities. RESULTS: Seventy-six percent of patients
      experienced pain during the past week. Chronic severe pain was experienced by
      29.1% of patients. High levels of pain interference with physical and
      psychosocial functioning were reported by 26.1%. Patients with chronic severe
      pain were more likely to have significant comorbidity, to cite physical pain as
      the impetus for alcohol or drug abuse, to have abused a prescription drug or used
      an illicit drug to treat pain during the prior 3 months, and to have used
      illicitly obtained opioids. Only 13% of patients with chronic severe pain were
      currently receiving pain treatment and 72% expressed interest in receiving
      treatment. DISCUSSION: Chronic severe pain was prevalent in this predominantly
      employed, alcoholic population attending an outpatient drug and alcohol treatment
      program. Pain was associated with significant functional impairment, medical and
      psychiatric comorbidities, and abuse behaviors. Few patients accessed adequate
      pain treatment. Efforts should be made to better address the pain problems in
      this patient population.

PMID- 18346065
TI  - Quality of chronic pain websites.
AB  - BACKGROUND: The Web not only can play a role in helping patients learn about
      their chronic pain, but can also be a source of misleading or untrue information.
      This study evaluates the quality of Internet information available concerning
      chronic pain at different sites, and determines the relation between quality and
      the source and character of the Websites. METHODS: A survey was conducted of
      patients seen at the Pain Management Center at Dartmouth-Hitchcock Medical Center
      (DHMC). Patients with access to the Internet identified the five most common
      keywords they used to look up information: pain, chronic pain, back pain,
      arthritis, and fibromyalgia. A focus group of pain clinicians at DHMC then chose
      the quality criteria to evaluate Websites. The criteria consisted of 16 items in
      five domains: etiology, diagnosis, goals of treatment, treatment options, and
      substance abuse. The first two pages of links displayed by each of three major
      search engines then were assessed for quality. RESULTS: A total of 240 Websites
      were evaluated. The mean score, the Quality Website Index (QWI), was 2.17 (SD =
      3.3), (range from -16 [poorest] to +16 [best]). The overall quality of this group
      of Websites is rather poor, although there were several excellent sites. Websites
      located on the main search page had a significantly higher score than those in
      the sponsored section, and Websites based on standards had a significantly higher
      score than those that were not. CONCLUSION: Based on QWI scores, clinicians can
      recommend chronic pain Websites to provide their patients with accurate and
      pertinent information.

PMID- 18346066
TI  - Safety of multiple, simultaneous continuous peripheral nerve block catheters in a
      patient receiving therapeutic low-molecular-weight heparin.
AB  - OBJECTIVE: The application of continuous peripheral nerve block (CPNB) has been
      an important anesthetic tool in the management of combat soldiers wounded from
      current conflicts. Placing and maintaining CPNBs becomes a challenge in this
      patient population due to concomitant prophylactic and therapeutic
      anticoagulation. CASE REPORT: A 32-year-old male sustained multiple traumatic
      injuries from an improvised explosive device, including a right tibial fracture,
      a left tibial fracture, and a left ulnar fracture. His pain was originally well
      controlled with a left infraclavicular CPNB (0.2% ropivacaine at 10 mL/h with 3
      mL bolus every 20 minutes) and an epidural (0.2% ropivacaine at 10 mL/h with 5 mL
      bolus every 30 minutes). He subsequently developed a common femoral vein thrombus
      and was treated with low-molecular-weight heparin. His epidural catheter was
      discontinued; however, his pain was not well controlled with intravenous and oral
      pain medication. We elected to place bilateral, tunneled sciatic CPNBs and a
      left, tunneled femoral CPNB. We started infusions of 0.2% ropivacaine at 10 mL/h
      in each catheter, in addition to 5 mL every 30 minutes demand dose in each
      sciatic catheter. The patient's serum ropivacaine levels were analyzed 24 hours
      after the start of the infusions and were found to be 5.8 mg/L and <0.1 mg/L for
      total and free concentrations, respectively. CONCLUSIONS: This case highlights
      the application of simultaneous CPNB techniques in a patient with multiple
      extremity injuries receiving anticoagulant therapy.

PMID- 18346067
TI  - Treatment of pain in Dercum's disease with Lidoderm (lidocaine 5% patch): a case
      report.
AB  - INTRODUCTION: Dercum's disease is a rare disorder characterized by multiple
      painful subcutaneous lipomas on the trunk and extremities. It most commonly
      occurs in obese, postmenopausal women. The pain associated with this condition is
      postulated to arise from enlarging lipomas producing pressure on peripheral
      nerves, thereby initiating pain and sometimes paresthesias. Treatment has been
      challenging due to the rarity of this condition. CASE: A patient with Dercum's
      disease successfully treated with transdermal lidocaine 5% patches. The patient's
      pain was initially rated as an 8/10. At follow-up examination after 1 month, the
      patient rated her pain as 3/10--a >60% reduction in pain; this pain reduction
      persisted at subsequent 1-month follow-up intervals. CONCLUSION: Current
      therapeutic options in the treatment of Dercum's disease have proven either
      ineffective or cumbersome. The use of transdermal lidocaine is a safe and non
      invasive treatment modality that has been efficacious in alternate forms. The use
      of this medication might prove preferable to more invasive or risky treatment and
      warrants further investigation.

PMID- 18346068
TI  - Referred pain elicited by manual exploration of the lateral rectus muscle in
      chronic tension-type headache.
AB  - OBJECTIVE: To analyze the presence of referred pain elicited by manual
      examination of the lateral rectus muscle in patients with chronic tension-type
      headache (CTTH). DESIGN: A case-control blinded study. SETTING: It has been found
      previously that the manual examination of the superior oblique muscle can elicit
      referred pain to the head in some patients with migraine or tension-type
      headache. However, a referred pain from other extraocular muscles has not been
      investigated. METHODS: Fifteen patients with CTTH and 15 healthy subjects without
      headache history were included. A blinded assessor performed a manual examination
      focused on the search for myofascial trigger points (TrPs) in the right and left
      lateral rectus muscles. TrP diagnosis was made when there was referred pain
      evoked by maintained pressure on the lateral corner of the orbit (anatomical
      projection of the lateral rectus muscle) for 20 seconds, and increased referred
      pain while the subject maintained a medial gaze on the corresponding side (active
      stretching of the muscle) for 15 seconds. On each side, a 10-point numerical pain
      rate scale was used to assess the intensity of referred pain at both stages of
      the examination. RESULTS: Ten patients with CTTH (66.6%) had referred pain that
      satisfied TrPs diagnostic criteria, while only one healthy control (0.07%)
      reported referred pain upon the examination of the lateral rectus muscles (P <
      0.001). The elicited referred pain was perceived as a deep ache located at the
      supraorbital region or the homolateral forehead. Pain was evoked on both sides in
      all subjects with TrPs, with no difference in pain intensity between the right
      and the left. The average pain intensity was significantly greater in the patient
      group (P < 0.001). All CTTH patients with referred pain recognized it as the
      frontal pain that they usually experienced during their headache attacks, which
      was consistent with active TrPs. CONCLUSION: In some patients with CTTH, the
      manual examination of lateral rectus muscle TrPs elicits a referred pain that
      extends to the supraorbital region or the homolateral forehead. Nociceptive
      inputs from the extraocular muscles may sustain the activation of trigeminal
      neuron, thus sensitizing central pain pathways and exacerbating headache.

PMID- 18346069
TI  - Prevalence and clinical correlates of vitamin D inadequacy among patients with
      chronic pain.
AB  - OBJECTIVE: Vitamin D inadequacy is associated with medication refractory
      musculoskeletal pain and neuromuscular dysfunction. This vitamin deficiency could
      subsist as an unrecognized comorbid condition among patients with chronic pain.
      The primary objective of this study was to determine the prevalence and clinical
      correlates of vitamin D inadequacy in patients seeking treatment for chronic
      pain. DESIGN: Retrospective case series. SETTING: Multidisciplinary pain
      rehabilitation center at a tertiary referral medical center. PATIENTS: The study
      involved 267 chronic pain patients admitted from February to December 2006.
      INTERVENTION: Serum 25-hydroxyvitamin D (25[OH]D) was drawn at admission. OUTCOME
      MEASURES: Patients with serum 25[OH]D levels < or=20 ng/mL were considered to
      have inadequate levels and those with levels >20 ng/mL were considered to have
      adequate levels. Upon admission, opioid intake was documented and patients
      completed the Short Form-36 Health Status Questionnaire. RESULTS: The prevalence
      of vitamin D inadequacy was 26% (95% confidence interval, 20.6-31.1%). Among
      patients using opioids, the mean morphine equivalent dose for the inadequate
      vitamin D group was 133.5 mg/day compared with 70.0 mg/day for the adequate group
      (P = 0.001). The mean duration of opioid use for the inadequate and adequate
      groups were 71.1 months and 43.8 months, respectively (P = 0.023). Opioid users
      with inadequate levels reported worse physical functioning (P = 0.041) and health
      perception (P = 0.003) than opioid users with adequate levels. CONCLUSION: The
      prevalence and clinical correlates identified in this pilot study provide the
      basis for the assertion that vitamin D inadequacy may represent an under
      recognized source of nociception and impaired neuromuscular functioning among
      patients with chronic pain.

PMID- 18346070
TI  - Translational control of photosynthetic gene expression in phototrophic
      eukaryotes.
AB  - It is getting more and more evident that photosynthetic gene expression is fine
      tuned by translation regulation factors encoded in the nucleus of photosynthetic
      cells. The research of the past decades led to the identification of several
      nucleus-encoded protein factors that recognize cis-acting elements in plastid
      transcripts, thereby modulating the stoichiometry and abundance of photosynthetic
      multisubunit complexes. Despite of its importance for photoacclimatory processes,
      the investigation of pathways that regulate translation of nuclear-encoded
      photosynthetic genes is still in its infancy. This review summarizes the yet
      known paradigms of translation control in chloroplast and cytosol of
      photosynthetic eukaryotes.

PMID- 18346071
TI  - Reactive oxygen signaling and abiotic stress.
AB  - Reactive oxygen species (ROS) play a dual role in plant biology acting on the one
      hand as important signal transduction molecules and on the other as toxic by
      products of aerobic metabolism that accumulate in cells during different stress
      conditions. Because of their toxicity as well as their important signaling role,
      the level of ROS in cells is tightly controlled by a vast network of genes termed
      the 'ROS gene network'. Using mutants deficient in key ROS-scavenging enzymes, we
      have defined a signaling pathway that is activated in cells in response to ROS
      accumulation. Interestingly, many of the key players in this pathway, including
      different zinc finger proteins and WRKY transcription factors, are also central
      regulators of abiotic stress responses involved in temperature, salinity and
      osmotic stresses. Here, we describe our recent findings and discuss how ROS
      integrate different signals originating from different cellular compartments
      during abiotic stress.

PMID- 18346072
TI  - Development of gene expression system in a marine diatom using viral promoters of
      a wide variety of origin.
AB  - Promoter sequences of the cytomegalovirus (PCMV), the rous sarcoma virus long
      terminal repeat (PRSV-LTR) and the cauliflower mosaic virus 35s (PCaMV35s) were
      ligated with the beta-glucuronidase (GUS) gene, uidA, and were introduced into
      cells of the marine diatom, Phaeodactylum tricornutum. Transformants were
      selected on a 100 mg l(-1) Zeocin plate, and Zeocin-resistant clones were further
      selected by the occurrence of GUS activity. Two to 10 GUS-positive clones were
      obtained, and GUS activities in these transformants did not change in response to
      changes in ambient CO(2) concentration except that the PRSV-LTR was weakly
      activated in air. These results indicate that a wide spectrum of viral promoters
      originating from mammalian, avian and plant hosts can operate as constitutive
      promoters in a marine diatom. The CO(2) responsive promoter sequence of the
      chloroplastic carbonic anhydrase gene in P. tricornutum (Pptca1) with a deleted
      initiator region was ligated with the minimal region of the PCMV followed by uidA
      and was introduced into P. tricornutum. GUS expression in the resulting
      transformants was clearly regulated by CO(2), that is, GUS expression was
      stimulated in air to about 10-fold than that in cells grown in 5% CO(2). However,
      the CO(2) response disappeared when the core regulatory region of Pptca1 (-76 to 
      11 bp) was removed. The regulative function of the endogenous diatom promoter was
      thus maintained after fusion with an extrinsic viral promoter. These results
      indicate that diatom cells accommodate a wide range of transcriptional system
      from beyond the plant kingdom and that an efficient transcriptional system could
      potentially be constructed in marine diatoms by selecting an appropriate set of
      viral promoter and functional cis elements.

PMID- 18346073
TI  - NTRC new ways of using NADPH in the chloroplast.
AB  - Despite being the primary source of energy in the biosphere, photosynthesis is a
      process that inevitably produces reactive oxygen species. Chloroplasts are a
      major source of hydrogen peroxide production in plant cells; therefore, different
      systems for peroxide reduction, such as ascorbate peroxidase and peroxiredoxins
      (Prxs), are found in this organelle. Most of the reducing power required for
      hydrogen peroxide reduction by these systems is provided by Fd reduced by the
      photosynthetic electron transport chain; hence, the function of these systems is
      highly dependent on light. Recently, it was described a novel plastidial enzyme,
      stated NTRC, formed by a thioredoxin reductase (NTR) domain at the N-terminus and
      a thioredoxin (Trx) domain at the C-terminus. NTRC is able to conjugate both NTR
      and Trx activities to efficiently reduce 2-Cys Prx using NADPH as a source of
      reducing power. Based on these results, it was proposed that NTRC is a new
      pathway to transfer reducing power to the chloroplast detoxification system,
      allowing the use of NADPH, besides reduced Fd, for such function. In this
      article, the most important features of NTRC are summarized and the implications
      of this novel activity in the context of chloroplast protection against oxidative
      damage are discussed.

PMID- 18346074
TI  - Vein recovery from embolism occurs under negative pressure in leaves of sunflower
      (Helianthus annuus).
AB  - Leaf veins undergo cavitation at water potentials (Psi(leaf)) commonly
      experienced by field-growing plants. Theoretically, embolism reversal should not
      be possible until xylem pressures rise by several kilopascals of atmospheric
      pressure, but recent evidence suggests that embolized conduits can be refilled
      even when surrounded by others at substantial tension (novel refilling). The
      present study reports 'novel refilling' occurring in leaf veins of sunflower
      (Helianthus annuus L.) while at Psi(leaf) = -0.33 MPa. Sixty per cent loss of
      vein hydraulic conductance (K(vein)) was recorded at Psi(leaf) < -0.65 MPa, while
      stem hydraulic conductance (K(stem)) was unaffected even at Psi(leaf) = -1.1 MPa.
      Loss of K(vein) was accompanied by stomatal closure. Water-stressed plants
      (Psi(leaf) = -1.1 MPa) were rehydrated overnight to different target water
      potentials achieved by using PEG at different concentrations as irrigation
      medium. K(vein) recovered by 50% at Psi(leaf) = -0.47 MPa and vein refilling was
      complete at Psi(leaf) = -0.33 MPa, i.e. well below the theoretical limit for
      conduit refilling (-0.05 MPa as calculated for sunflower minor veins). Mercurials
      supplied to detached leaves had no effect on the refilling process. Upon
      rehydration, recovery of K(vein) was not paralleled by recovery of whole-plant
      hydraulic conductance or leaf conductance to water vapour (g(L)), as a likely
      consequence of hydraulic failure of other components of the water pathway (root
      system or extravascular leaf compartments) and/or root-to-leaf chemical
      signalling. This is the first study providing experimental evidence for 'novel
      refilling' in a herbaceous dicot and highlighting the importance of this process
      in the leaf.

PMID- 18346075
TI  - Relationship between the photosynthetic activity and the performance of Cakile
      maritima after long-term salt treatment.
AB  - Cakile maritima is a halophyte with potential for ecological, economical and
      medicinal uses. We address here the impact of salinity on its growth,
      photosynthesis and seed quality. Whole plant growth rate and shoot development
      were stimulated at moderate salinity (100-200 mM NaCl) and inhibited at higher
      salt concentrations. Although diminished in the presence of salt, potassium and
      calcium uptake per unit of root biomass was maintained at relatively high value,
      while nutrient-use efficiency (NUE) was improved in salt-treated plants. Chl and
      carotenoid concentrations decreased at extreme salinities, but anthocyanin
      concentration continuously grew with salinity. Net photosynthetic rate (A),
      stomatal conductance, maximum quantum efficiency of PSII and quantum yield were
      stimulated in the 100-200 mM NaCl range. Higher salinity adversely affected gas
      exchange and changed PSII functional characteristics, resulting in a reduction of
      A per leaf area unit. This phenomenon was associated with increased non
      photochemical quenching. Harvest index, silique number and seeds per fruit valve
      were maximal at 100 mM NaCl. Despite the decreasing salt accumulation gradient
      from the vegetative to the reproductive organs, high salinities were detrimental
      for the seed viability and increased the proportion of empty siliques. Overall,
      the salt-induced changes in the plant photosynthetic activity resulted into
      analogous responses at the vegetative and reproductive stages. The enhancement of
      NUE, the absence of pigment degradation, the reduction of water loss and the
      concomitant PSII protection from photodamage through thermal dissipation of
      excess excitation significantly accounted for Cakile survival capacity at high
      salinity.

PMID- 18346076
TI  - Role of nitric oxide in actin depolymerization and programmed cell death induced
      by fusicoccin in sycamore (Acer pseudoplatanus) cultured cells.
AB  - Programmed cell death (PCD) plays a vital role in plant development and is
      involved in defence mechanisms against biotic and abiotic stresses. Different
      forms of PCD have been described in plants on the basis of the cell organelle
      first involved. In sycamore (Acer pseudoplatanus L.) cultured cells, the
      phytotoxin fusicoccin (FC) induces cell death. However, only a fraction of the
      dead cells shows the typical hallmarks of animal apoptosis, including cell
      shrinkage, chromatin condensation, DNA fragmentation and release of cytochrome c
      from the mitochondrion. In this work, we show that the scavenging of nitric oxide
      (NO), produced in the presence of FC, by 2-(4-carboxyphenyl)-4,4,5,5
      tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) and rutin inhibits cell death
      without affecting DNA fragmentation and cytochrome c release. In addition, we
      show that FC induces a massive depolymerization of actin filaments that is
      prevented by the NO scavengers. Finally, the addition of actin-depolymerizing
      drugs induces PCD in control cells and overcomes the inhibiting effect of cPTIO
      on FC-induced cell death. Vice versa, the addition of actin-stabilizing drugs to
      FC-treated cells partially inhibits the phytotoxin-induced PCD. These results
      suggest that besides an apoptotic-like form of PCD involving the release of
      cytochrome c, FC induces at least another form of cell death, likely mediated by
      NO and independent of cytochrome c release, and they make it tempting to
      speculate that changes in actin cytoskeleton are involved in this form of PCD.

PMID- 18346077
TI  - Diurnal changes in epidermal UV transmittance of plants in naturally high UV
      environments.
AB  - Studies were conducted on three herbaceous plant species growing in naturally
      high solar UV environments in the subalpine of Mauna Kea, Hawaii, USA, to
      determine if diurnal changes in epidermal UV transmittance (T(UV)) occur in these
      species, and to test whether manipulation of the solar radiation regime could
      alter these diurnal patterns. Additional field studies were conducted at Logan,
      Utah, USA, to determine if solar UV was causing diurnal T(UV) changes and to
      evaluate the relationship between diurnal changes in T(UV) and UV-absorbing
      pigments. Under clear skies, T(UV), as measured with a UV-A-pulse amplitude
      modulation fluorometer for leaves of Verbascum thapsus and Oenothera stricta
      growing in native soils and Vicia faba growing in pots, was highest at predawn
      and sunset and lowest at midday. These patterns in T(UV) closely tracked diurnal
      changes in solar radiation and were the result of correlated changes in
      fluorescence induced by UV-A and blue radiation but not photochemical efficiency
      (F(v)/F(m)) or initial fluorescence yield (F(o)). The magnitude of the midday
      reduction in T(UV) was greater for young leaves than for older leaves of
      Verbascum. Imposition of artificial shade eliminated the diurnal changes in T(UV)
      in Verbascum, but reduction in solar UV had no effect on diurnal T(UV) changes in
      Vicia. In Vicia, the diurnal changes in T(UV) occurred without detectable changes
      in the concentration of whole-leaf UV-absorbing compounds. Results suggest that
      plants actively control diurnal changes in UV shielding, and these changes occur
      in response to signals other than solar UV; however, the underlying mechanisms
      responsible for rapid changes in T(UV) remain unclear.

PMID- 18346078
TI  - EIN3-like gene expression during fruit ripening of Cavendish banana (Musa
      acuminata cv. Grande naine).
AB  - Ethylene signal transduction initiates with ethylene binding at receptor proteins
      and terminates in a transcription cascade involving the EIN3/EIL transcription
      factors. Here, we have isolated four cDNAs homologs of the Arabidopsis EIN3/EIN3
      like gene, MA-EILs (Musa acuminata ethylene insensitive 3-like) from banana
      fruit. Sequence comparison with other banana EIL gene already registered in the
      database led us to conclude that, at this day, at least five different genes
      namely MA-EIL1, MA-EIL2/AB266318, MA-EIL3/AB266319, MA-EIL4/AB266320 and AB266321
      exist in banana. Phylogenetic analyses included all banana EIL genes within a
      same cluster consisting of rice OsEILs, a monocotyledonous plant as banana.
      However, MA-EIL1, MA-EIL2/AB266318, MA-EIL4/AB266320 and AB266321 on one side,
      and MA-EIL3/AB266319 on the other side, belong to two distant subclusters. MA-EIL
      mRNAs were detected in all examined banana tissues but at lower level in peel
      than in pulp. According to tissues, MA-EIL genes were differentially regulated by
      ripening and ethylene in mature green fruit and wounding in old and young leaves.
      MA-EIL2/AB266318 was the unique ripening- and ethylene-induced gene; MA-EIL1, MA
      EIL4/Ab266320 and AB266321 genes were downregulated, while MA-EIL3/AB266319
      presented an unusual pattern of expression. Interestingly, a marked change was
      observed mainly in MA-EIL1 and MA-EIL3/Ab266319 mRNA accumulation concomitantly
      with changes in ethylene responsiveness of fruit. Upon wounding, the main effect
      was observed in MA-EIL4/AB266320 and AB266321 mRNA levels, which presented a
      markedly increase in both young and old leaves, respectively. Data presented in
      this study suggest the importance of a transcriptionally step control in the
      regulation of EIL genes during banana fruit ripening.

PMID- 18346079
TI  - Light-induced transpiration alters cell water relations in figleaf gourd
      (Cucurbita ficifolia) seedlings exposed to low root temperatures.
AB  - Water relation parameters including elastic modulus (epsilon), half-times of
      water exchange (T(w)(1/2)), hydraulic conductivity and turgor pressure (P) were
      measured in individual root cortical and cotyledon midrib cells in intact figleaf
      gourd (Cucurbita ficifolia) seedlings, using a cell pressure probe. Transpiration
      rates (E) of cotyledons were also measured using a steady-state porometer. The
      seedlings were exposed to low ambient (approximately 10 micromol m(-2) s(-1)) or
      high supplemental irradiance (approximately 300 micromol m(-2) s(-1) PPF density)
      at low (8 degrees C) or warm (22 degrees C) root temperatures. When exposed to
      low irradiance, all the water relation parameters of cortical cells remained
      similar at both root temperatures. The exposure of cotyledons to supplemental
      light at warm root temperatures, however, resulted in a two- to three-fold
      increase in T(w)(1/2) values accompanied with the reduced hydraulic conductivity
      in both root cortical (Lp) and cotyledon midrib cells (Lp(c)). Low root
      temperature (LRT) further reduced Lp(c) and E, whether it was measured under low
      or high irradiance levels. The reductions of Lp as the result of respective light
      and LRT treatments were prevented by the application of 1 microM ABA. Midrib
      cells required higher concentrations of ABA (2 microM) in order to prevent the
      reduction in Lp(c). When the exposure of cotyledons to light was accompanied by
      LRT, however, ABA proved ineffective in reversing the inhibition of Lp. LRT
      combined with high irradiance triggered a drastic 10-fold reduction in water
      permeability of cortical and midrib cells and increased epsilon and T(w)(1/2)
      values. Measurement of E indicated that the increased water demand by the
      transpiring plants was fulfilled by an increase in the apoplastic pathway as
      principal water flow route. The importance of water transport regulation by
      transpiration affecting the hydraulic conductivity of the roots is discussed.

PMID- 18346080
TI  - The chemistry behind redox regulation with a focus on sulphur redox systems.
AB  - Sulphur metabolism in plants provides a wealth of natural products, including
      several chemically unusual substances, such as thiosulphinates, polysulphides and
      isothiocyanates. Many of these reactive sulphur species (RSS) exhibit a distinct
      redox behaviour in vitro, which translates into a rather interesting biological
      activity in vivo, such as antibiotic, fungicidal, pesticidal or anticancer
      activity. While the molecular basis for such activity has long remained obscure,
      research into sulphur-based redox systems during the past 5-10 years has achieved
      a better knowledge of the in vitro properties of RSS and has led to an improved
      understanding of their impact on intracellular redox signalling and control
      pathways in living cells. It has become apparent that the redox chameleon sulphur
      occurs in biological systems in about 10 different oxidation states, which give
      rise to an extensive and complicated network of sulphur-based redox events.
      Together, natural sulphur products from plants and their intracellular targets
      provide the basis for innovative design of novel antibiotics, fungicides,
      pesticides and anticancer agents.

PMID- 18346081
TI  - Non-photochemical loss in PSII in high- and low-light-grown leaves of Vicia faba
      quantified by several fluorescence parameters including L(NP), F0/F'm, a novel
      parameter.
AB  - Using the expression of fluorescence originated from the PSII open reaction
      center in the light by Oxborough and Baker (1997), we obtained a formula that
      expresses relationships between the quantum efficiency of PSII photochemistry in
      the dark (Phi(m)= F(v)/F(m)) and in the light
      Phi'(m)=F'(v)/F'(m):Phi'(m)=Phi(m)+L(NP), where L(NP)(=F(0)/F'(m)) denotes the
      quantum yield of light induced non-photochemical losses (heat dissipation and
      fluorescence de-excitation) in PSII. Using L(NP) and other conventional
      fluorescence parameters, we conducted quenching analyses with leaves of broad
      bean plants (Vicia faba L.) grown at 700 (high light; HL) and 80 mumol photons m(
      2) s(-1) (low light; LL). We also examined whether behavior of q(0) quenching
      (q(0)=1-F'(0)/F(0)) is related to the reaction center quenching. When the actinic
      light (AL) was strong, Stern-Volmer quenching [NPQ=(F(m)-F'(m))/F'(m)] and L(NP)
      increased rapidly and then decreased slowly in HL leaves, while, in LL leaves,
      they increased slowly. It is probable that rapid formation of a large proton
      gradient was responsible for sharp rises in both parameters in HL leaves. The
      steady-state 'excess' parameter [Phi(Ex)= (1 - qP) Phi(m)/(Phi(m)+ L(NP))],
      fraction of energy migrating to closed PSII centers, increased with the photon
      flux density of AL in LL leaves. In contrast, in HL leaves, Phi(Ex) did not
      increase markedly. The examination of the relationship between Phi(Ex) and L(NP)
      obtained at various AL revealed that in LL leaves the increase in (1 - qP) with
      the increase in AL prevailed, while, in HL leaves, the increase in L(NP)
      suppressed the increase in (1 - qP). Using the difference between L(NP) and L(D)
      (Phi(ND)= L(NP)- L(D), where L(D)= F(0)/F(m)), q(0) and qN (=1-F'(v)/F(v)) were
      calculated without using measured F'(0). The relationships between q(0) and qN
      thus obtained for various AL levels were almost identical for both HL and LL
      leaves, implying no difference in the fluorescence origin between the HL and LL
      leaves. Usefulness of these equations expressing non-photochemical loss is
      discussed.

PMID- 18346082
TI  - Exogenous ammonium inhibits petal pigmentation and expansion in Gerbera hybrida.
AB  - Petal pigmentation is the most important aspect in natural flower coloration. In
      the present study, the inhibition of petal pigmentation by exogenous ammonium was
      investigated. Ray floret petals detached from inflorescences of Gerbera hybrida
      (Shenzhen No. 5) were cultured in vitro on media supplied with different forms of
      nitrogen and its assimilated compounds. The expression of a set of genes involved
      in anthocyanin biosynthesis and regulation was determined by Northern blotting
      assay. It was found that ammonium (NH4+), not nitrate (NO3-), in millimolar
      concentrations inhibited anthocyanin accumulation. The expressions of Gerbera
      chalcone synthase 1 (GCHS1), Gerbera chalcone synthase 2 (GCHS2) and Gerbera
      dihydroflavonol-4-reductase (GDFR) decreased, while six other related genes
      showed no significant changes after NH4+ treatment. Further studies on NH4+
      function indicated that glutamine (Gln) acted as a downstream factor of NH4+ to
      suppress petal pigmentation. Both exogenous Gln and NH4+ were found to inhibit
      anthocyanin accumulation in the petals, and the application of Gln was also found
      to inhibit the expressions of GCHS1, GCHS2 and GDFR. The application of NH4+ also
      resulted in an increase in the activity of Gerbera glutamine synthetase (EC
      6.3.1.2) along with a rapid increase of Gln content. When methionine sulfoximine,
      an inhibitor of glutamine synthetase (GS), was added, it was found to block the
      NH4+-induced inhibition of pigmentation. From these experiments, we conclude that
      the NH4+-induced suppression of petal pigmentation is not because of NH4+
      toxicity, and the inhibition of pigmentation caused by the addition of exogenous
      NH4+ is the result of its assimilation into Gln.

PMID- 18346083
TI  - Purification, cloning and functional differences of a third fructan 1
      exohydrolase (1-FEHw3) from wheat (Triticum aestivum).
AB  - A third fructan exohydrolase isoform (1-FEHw3) was purified from wheat stems by a
      combination of ammonium sulfate precipitation, ConA affinity and ion-exchange
      chromatography. Homogeneity of the preparation was indicated by the presence of a
      single band (70 kDa) after SDS-PAGE. The enzyme hydrolyzed mainly beta2-1
      linkages in fructans and was inhibited by sucrose. A cDNA could be obtained after
      reverse transcriptase polymerase chain reaction (RT-PCR)-based strategies and
      screening of a cDNA library. Functionality tests of the cDNA performed after
      heterologous expression in the yeast Pichia pastoris showed that the encoded
      protein has essentially the same characteristics as the native enzyme. Homology
      with previously described 1-FEH isoforms from wheat was high (97% identity), and
      the enzyme showed minor differences to the previously published enzymes. The
      relative abundance of 1-FEH transcripts in different tissues was investigated by
      using quantitative RT-PCR.

PMID- 18346084
TI  - The photoreaction of the photoactive yellow protein domain in the light sensor
      histidine kinase Ppr is influenced by the C-terminal domains.
AB  - To study the role of the C-terminal domains in the photocycle of a light sensor
      histidine kinase (Ppr) having a photoactive yellow protein (PYP) domain as the
      photosensor domain, we analyzed the photocycles of the PYP domain of Ppr (Ppr
      PYP) and full-length Ppr. The gene fragment for Ppr-PYP was expressed in
      Escherichia coli, and it was chemically reconstituted with p-coumaric acid; the
      full-length gene of Ppr was coexpressed with tyrosine ammonia-lyase and p
      coumaric acid ligase for biosynthesis in cells. The light/dark difference spectra
      of Ppr-PYP were pH sensitive. They were represented as a linear combination of
      two independent difference spectra analogous to the PYP(L)/dark and PYP(M)/dark
      difference spectra of PYP from Halorhodospira halophila, suggesting that the pH
      dependence of the difference spectra is explained by the equilibrium shift
      between the PYP(L)- and PYP(M)-like intermediates. The light/dark difference
      spectrum of Ppr showed the equilibrium shift toward PYP(L) compared with that of
      Ppr-PYP. Kinetic measurements of the photocycles of Ppr and Ppr-PYP revealed that
      the C-terminal domains accelerate the recovery of the dark state. These
      observations suggest an interaction between the C-terminal domains and the PYP
      domain during the photocycle, by which light signals captured by the PYP domain
      are transferred to the C-terminal domains.

PMID- 18346085
TI  - Alpha-retinals as rhodopsin chromophores--preference for the 9-Z configuration
      and partial agonist activity.
AB  - The visual pigment rhodopsin, the photosensory element of the rod photoreceptor
      cell in the vertebrate retina, shows in combination with an endogenous ligand, 11
      Z retinal, an astonishing photochemical performance. It exhibits an unprecedented
      quantum yield (0.67) in a highly defined and ultrafast photoisomerization
      process. This triggers the conformational changes leading to the active state
      Meta(rhodopsin) II. Retinal is covalently bound to Lys-296 of the protein opsin
      in a protonated Schiff base. The resulting positive charge delocalization over
      the terminal part of the polyene chain of retinal creates a conjugation defect
      that upon photoexcitation moves to the opposite end of the polyene. Shortening
      the polyene as in 4,5-dehydro,5,6-dihydro (alpha), 5,6-dihydro or 7,8-dihydro
      analogs might facilitate photoisomerization of a 9-Z and a 11-Z bond. Here we
      describe pigment analogs generated with bovine opsin and 11-Z or 9-Z 4,5
      dehydro,5,6-dihydro-retinal that were further characterized by UV-Vis and FTIR
      spectroscopy. The preference of opsin for native 11-Z retinal over the 9-Z isomer
      is reversed in 4,5-dehydro,5,6-dihydro-retinal. 9-Z 4,5-dehydro,5,6-dihydro
      retinal readily generated a photosensitive pigment. This modification has no
      effect on the quantum yield, but affects the Batho<-->blueshifted intermediate
      (BSI) equilibrium and leads to a strong decrease in the G-protein activation rate
      because of a downshift of the pK(a) of the Meta I<-->Meta II equilibrium.

PMID- 18346086
TI  - Vitamin B-sensitized photo-oxidation of dopamine.
AB  - Kinetics and mechanism of the photo-oxidation of the natural catecholamine-type
      neurotransmitter dopamine (DA) has been studied in aqueous solution, under
      aerobic conditions, in the presence of riboflavin (Rf, vitamin B(2)) as a
      photosensitizer. Results indicate the formation of a weak dark complex Rf-DA,
      with a mean apparent association constant K(ass) = 30 m(-1), only detectable at
      DA concentrations much higher than those employed in photochemical experiments.
      An intricate mechanism of competitive reactions operates upon photoirradiation.
      DA quenches excited singlet and triplet states of Rf, with rate constants of 4.2
      x 10(9) and 2.2 x 10(9) m(-1) s(-1), respectively. With the catecholamine in a
      concentration similar to that of dissolved molecular oxygen in air-saturated
      water, DA and oxygen competitively quench the triplet excited state of Rf,
      generating superoxide radical anion (O(2)) and singlet molecular oxygen
      (O(2)((1)Delta(g))) by processes initiated by electron and energy-transfer
      mechanisms, respectively. Rate constants values of 1.9 x 10(8) and 6.6 x 10(6) m(
      1) s(-1) have been obtained for the overall and reactive (chemical) interaction
      of DA with O(2)((1)Delta(g)). The presence of superoxide dismutase increases both
      the observed rates of aerobic DA photo-oxidation and oxygen uptake, due to its
      known catalytic scavenging of O(2), a species that could revert the overall photo
      oxidation effect, according to the proposed reaction mechanism. As in most of the
      catecholamine oxidative processes described in the literature, aminochrome is the
      DA oxidation product upon visible light irradiation in the presence of Rf. It is
      generated with a quantum yield of 0.05.

PMID- 18346087
TI  - The lifetimes of Pharaonis phoborhodopsin signaling states depend on the rates of
      proton transfers--effects of hydrostatic pressure and stopped flow experiments.
AB  - Pharaonis phoborhodopsin (ppR), a negative phototaxis receptor of Natronomonas
      pharaonis, undergoes photocycle similar to the light-driven proton pump
      bacteriorhodopsin (BR), but the turnover rate is much slower due to much longer
      lifetimes of the M and O intermediates. The M decay was shown to become as fast
      as it is in BR in the L40T/F86D mutant. We examined the effects of hydrostatic
      pressure on the decay of these intermediates. For BR, pressure decelerated M
      decay but slightly affected O decay. In contrast, with ppR and with its L40T/F86D
      mutant, pressure slightly affected M decay but accelerated O decay. Clearly, the
      pressure-dependent factors for M and O decay are different in BR and ppR. In
      order to examine the deprotonation of Asp75 in unphotolyzed ppR we performed
      stopped flow experiments. The pH jump-induced deprotonation of Asp75 occurred
      with 60 ms, which is at least 20 times slower than deprotonation of the
      equivalent Asp85 in BR and about 10-fold faster than the O decay of ppR. These
      data suggest that proton transfer is slowed not only in the cytoplasmic channel
      but also in the extracellular channel of ppR and that the light-induced
      structural changes in the O intermediate of ppR additionally decrease this rate.

PMID- 18346088
TI  - Protein-protein interaction of a Pharaonis halorhodopsin mutant forming a complex
      with Pharaonis halobacterial transducer protein II detected by Fourier-transform
      infrared spectroscopy.
AB  - Pharaonis halorhodopsin (pHR) functions as a light-driven inward chloride ion
      pump in Natoronomonas pharaonis, while pharaonis phoborhodopsin (ppR; also called
      pharaonis sensory rhodopsin II, pSRII), is a light sensor for negative
      phototaxis. ppR forms a 2:2 complex with its cognate transducer protein (pHtrII)
      through intramembranous hydrogen bonds: Tyr199(ppR)-Asn74(pHtrII) and Thr189(ppR)
      Glu43 (pHtrII), Ser62(pHtrII). It was reported that a pHR mutant (P240T/F250Y),
      which possesses the hydrogen-bonding sites, impairs its pumping activity upon
      complexation with pHtrII. In this study, effect of the complexation with pHtrII
      on the structural changes upon formation of the K, L(1) and L(2) intermediates of
      pHR was investigated by use of Fourier-transform infrared spectroscopy. The
      vibrational changes of Tyr250(pHR) and Asn74(pHtrII) were detected for the L(1)
      and L(2) intermediates, supporting that Tyr250(pHR) forms a hydrogen bond with
      Asn74(pHtrII) as similarly to Tyr199(ppR). The conformational changes of the
      retinal chromophore were never affected by complexation with pHtrII, but amide-I
      vibrations were clearly different in the absence and presence of pHtrII. The
      molecular environment around Asp156(pHR) in helix D is also slightly affected.
      These additional structural changes are probably related to blocking of
      translocation of a chloride ion from the extracellular to the cytoplasmic side
      during the photocycle.

PMID- 18346089
TI  - Role of ocular melanin in ophthalmic physiology and pathology.
AB  - The mammalian eye consists of several layers of pigmented tissues that contain
      melanin. The eye is a unique organ for pigment cell research because one can
      isolate and compare melanosomes from different tissues and embryonic origins.
      Retinal, iris and ciliary pigment epithelial cells are derived from the neural
      ectoderm, more specifically from the extremity of the embryonic optical cup,
      which is also the origin of the retina. In contrast, the pigment-generating cells
      in the choroid and in the stroma of the iris and ciliary body, uveal melanocytes,
      are developed from the neural crest, the same origin as the melanocytes in skin
      and hair. This review examines the potential functions of ocular melanin in the
      human eye. Following a discussion of the role of melanins in the pigment
      epithelium and uveal melanocytes, three specific topics are explored in detail
      photo-screening protective effects, biophysical and biochemical protective
      effects, and the biologic and photobiologic effects of the two main classes of
      melanins (generally found as mixtures in ocular melanosomes)--eumelanin and
      pheomelanin.

PMID- 18346090
TI  - Protein diffusion probed by the transient grating method with a new type of
      photochromic molecule.
AB  - A new type of photochromic molecule that can be used for diffusion coefficient
      (D) measurements of various proteins in solution is described. The absorption
      spectrum of this molecule is changed upon photoexcitation by the trans-cis
      isomerization reaction. Target proteins were labeled by this photochromic
      molecule in the dark and the translational motion of the proteins was detected by
      the transient grating (TG) method. The TG signal was simple enough to determine D
      accurately and was stable even for long-time irradiation by the laser light. The
      TG method using this probe molecule improves many drawbacks of the other
      techniques.

PMID- 18346091
TI  - Signal transfer in haloarchaeal sensory rhodopsin- transducer complexes.
AB  - Membrane-inserted complexes consisting of two photochemically reactive sensory
      rhodopsin (SR) subunits flanking a homodimer of a transducing protein subunit
      (Htr) are used by halophilic archaea for sensing light gradients to modulate
      their swimming behavior (phototaxis). The SR-Htr complexes extend into the
      cytoplasm where the Htr subunits bind a his-kinase that controls a
      phosphorylation system that regulates the flagellar motors. This review focuses
      on current progress primarily on the mechanism of signal relay within the SRII
      HtrII complexes from Natronomonas pharaonis and Halobacterium salinarum. The
      recent elucidation of a photoactive site steric trigger crucial for signal relay,
      advances in understanding the role of proton transfer from the chromophore to the
      protein in SRII activation, and the localization of signal relay to the membrane
      embedded portion of the SRII-HtrII interface, are beginning to produce a clear
      picture of the signal transfer process. The SR-Htr complexes offer unprecedented
      opportunities to resolve first examples of the chemistry of signal relay between
      membrane proteins at the atomic level, which would provide a major contribution
      to the general understanding of dynamic interactions between integral membrane
      proteins.

PMID- 18346092
TI  - Inactivation of lymphocytes in blood products using riboflavin photochemical
      treatment with visible light.
AB  - Immunocompetent lymphocytes present in blood products are an important cause of
      immune reactions following blood transfusion such as transfusion-associated graft
      versus-host disease (TA-GVHD). In this study the effects of riboflavin
      photochemical treatment (RPT) on lymphocyte proliferation and cytokine production
      in vitro were measured to establish whether RPT of blood products can be used to
      prevent immune reactions resulting from transfused lymphocytes. Lymphocytes and
      riboflavin were added together in medical PVC transparent bags and then exposed
      to visible light. Control lymphocytes were exposed to light in the absence of
      riboflavin. Lymphocytes exposed to riboflavin photochemical treatment (RPT
      lymphocytes) and control lymphocytes were tested for the proliferative ability
      and the production of several cytokines upon stimulation with antigens. Upon
      stimulation by phytohemagglutinin (PHA) the proliferation of RPT-lymphocytes was
      inhibited. Using flow cytometry it was shown that RPT-lymphocytes were unable to
      enter the S-phase of the cell cycle following PHA stimulation. The level of
      cytokines present in the supernatant of RPT-lymphocytes after stimulation by
      antigens was significantly lower than those present in the corresponding
      supernatant of control lymphocytes. RPT with visible light inactivates
      lymphocytes, inhibits lymphocyte proliferation and the production of cytokines.
      It appears to be a promising method to prevent immune reactions such as TA-GVHD.

PMID- 18346093
TI  - Ca2+ -dependent regulation of phototransduction.
AB  - Photon absorption by rhodopsin triggers the phototransduction signaling pathway
      that culminates in degradation of cGMP, closure of cGMP-gated ion channels and
      hyperpolarization of the photoreceptor membrane. This process is accompanied by a
      decrease in free Ca(2+) concentration in the photoreceptor cytosol sensed by
      Ca(2+)-binding proteins that modulate phototransduction and activate the recovery
      phase to reestablish the photoreceptor dark potential. Guanylate cyclase
      activating proteins (GCAPs) belong to the neuronal calcium sensor (NCS) family
      and are responsible for activating retinal guanylate cyclases (retGCs) at low
      Ca(2+) concentrations triggering synthesis of cGMP and recovery of the dark
      potential. Here we review recent structural insight into the role of the N
      terminal myristoylation in GCAPs and compare it to other NCS family members. We
      discuss previous studies identifying regions of GCAPs important for retGC1
      regulation in the context of the new structural data available for myristoylated
      GCAP1. In addition, we present a hypothetical model for the Ca(2+)-triggered
      conformational change in GCAPs and retGC1 regulation. Finally, we briefly discuss
      the involvement of mutant GCAP1 proteins in the etiology of retinal degeneration
      as well as the importance of other Ca(2+) sensors in the modulation of
      phototransduction.

PMID- 18346094
TI  - Interlinking showy traits: co-engineering of scent and colour biosynthesis in
      flowers.
AB  - The phenylpropanoid pathway gives rise to metabolites that determine floral
      colour and fragrance. These metabolites are one of the main means used by plants
      to attract pollinators, thereby ensuring plant survival. A lack of knowledge
      about factors regulating scent production has prevented the successful
      enhancement of volatile phenylpropanoid production in flowers. In this study, the
      Production of Anthocyanin Pigment1 (Pap1) Myb transcription factor from
      Arabidopsis thaliana, known to regulate the production of non-volatile
      phenylpropanoids, including anthocyanins, was stably introduced into Petunia
      hybrida. In addition to an increase in pigmentation, Pap1-transgenic petunia
      flowers demonstrated an increase of up to tenfold in the production of volatile
      phenylpropanoid/benzenoid compounds. The dramatic increase in volatile production
      corresponded to the native nocturnal rhythms of volatile production in petunia.
      The application of phenylalanine to Pap1-transgenic flowers led to an increase in
      the otherwise negligible levels of volatiles emitted during the day to nocturnal
      levels. On the basis of gene expression profiling and the levels of pathway
      intermediates, it is proposed that both increased metabolic flux and
      transcriptional activation of scent and colour genes underlie the enhancement of
      petunia flower colour and scent production by Pap1. The co-ordinated regulation
      of metabolic steps within or between pathways involved in vital plant functions,
      as shown here for two showy traits determining plant-pollinator interactions,
      provides a clear advantage for plant survival. The use of a regulatory factor
      that activates scent production creates a new biotechnological strategy for the
      metabolic architecture of fragrance, leading to the creation of novel genetic
      variability for breeding purposes.

PMID- 18346095
TI  - Generation of glyco-engineered Nicotiana benthamiana for the production of
      monoclonal antibodies with a homogeneous human-like N-glycan structure.
AB  - A common argument against using plants as a production system for therapeutic
      proteins is their inability to perform authentic human N-glycosylation (i.e. the
      presence of beta1,2-xylosylation and core alpha1,3-fucosylation). In this study,
      RNA interference (RNAi) technology was used to obtain a targeted down-regulation
      of the endogenous beta1,2-xylosyltransferase (XylT) and alpha1,3
      fucosyltransferase (FucT) genes in Nicotiana benthamiana, a tobacco-related plant
      species widely used for recombinant protein expression. Three glyco-engineered
      lines with significantly reduced xylosylated and/or core alpha1,3-fucosylated
      glycan structures were generated. The human anti HIV monoclonal antibody 2G12 was
      transiently expressed in these glycosylation mutants as well as in wild-type
      plants. Four glycoforms of 2G12 differing in the presence/absence of xylose and
      core alpha1,3-fucose residues in their N-glycans were produced. Notably, 2G12
      produced in XylT/FucT-RNAi plants was found to contain an almost homogeneous N
      glycan species without detectable xylose and alpha1,3-fucose residues. Plant
      derived glycoforms were indistinguishable from Chinese hamster ovary (CHO)
      derived 2G12 with respect to electrophoretic properties, and exhibited functional
      properties (i.e. antigen binding and HIV neutralization activity) at least
      equivalent to those of the CHO counterpart. The generated RNAi lines were stable,
      viable and did not show any obvious phenotype, thus providing a robust tool for
      the production of therapeutically relevant glycoproteins in plants with a
      humanized N-glycan structure.

PMID- 18346096
TI  - Bronchial obstructive phenotypes in the first year of life among Paris birth
      cohort infants.
AB  - As the natural history of respiratory and allergic manifestations is unclear, our
      ongoing Paris birth cohort study prospectively assesses the onset of these
      symptoms in early childhood. Data were collected by five questionnaires sent at
      regular intervals during the first year of life. Partitioning around medoids
      (PAM) was used to classify infants according to their bronchial obstructive
      symptoms. A polytomous logistic regression was performed to assess the eventual
      predictable power of various respiratory events and perinatal factors. Results
      are given for 2698 infants. Atopic dermatitis occurred in 17.9% of infants. The
      main respiratory symptoms in infancy were wheeze in the chest (22%), dyspnoea
      responsible for sleep disturbance (23.7%), nocturnal dry cough (14.5%) and
      shortness of breath (4.2%). The PAM method identified three groups of infants.
      Apart from the G0 group of infants mostly asymptomatic, two distinct clinical
      phenotypes (G1 and G2: 8.7% and 23.5% of total infants respectively) emerged. G2
      was defined by severe bronchial obstructive disorders as all cases of dyspnoea
      with sleep disturbance were included in this group, while all infants assigned in
      G1 suffered from nocturnal dry cough. G2 group infants had significantly higher
      rates of respiratory events while a parental history of asthma, symptoms
      suggestive of rhino-conjunctivitis and birth season clearly differentiated the G1
      group. Finally, G1 and G2 group infants should be closely followed up as they are
      expected to develop allergic and asthmatic phenotypes, possibly in relation to
      environmental and behavioural risk factors.

PMID- 18346097
TI  - High levels of IgG4 antibodies to foods during infancy are associated with
      tolerance to corresponding foods later in life.
AB  - Children with eczema and sensitization to foods are recommended skin care and, if
      food allergy is proven by challenge, an elimination diet. For most children the
      diet period is transient, but the process behind tolerance development and the
      influence of decreased allergen exposure is not fully known. The aim of the study
      was to investigate the effect of elimination diet on serum and salivary
      antibodies and to identify immunological parameters related to the ability to
      tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and
      suspected food allergy were included. Recommended treatment was skin care to all
      children, and 60 children had a period of elimination diet. At 4(1/2) yr of age,
      the children were divided into two groups, based on if they had been able to
      introduce the eliminated foods, or not. Serum and salivary antibodies were
      analyzed with enzyme-linked immunosorbent assay and UniCAP before and after a 6
      wk treatment period and at 4(1/2) yr of age. Children sensitized to egg and/or
      milk that could eat and drink the offending foods at 4(1/2) yr of age, had higher
      levels of Immunoglobulin G(4) antibodies to ovalbumin and beta-lactoglobulin and
      also higher IgG(4)/Immunoglobulin E ratios on inclusion in the study, than those
      who had to eliminate egg and/or milk from their diet, beyond 4(1/2) yr of age.
      The highest IgG(4)/IgE ratios were found in children with circulating IgE
      antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk
      treatment period did not significantly affect the levels of serum and salivary
      antibodies. In conclusion, eczematous, food sensitized infants with high levels
      of IgG(4) and high ratios of IgG(4)/IgE antibodies to food allergens are more
      likely to consume these foods at 4(1/2) yr than infants with low levels and
      ratios.

PMID- 18346098
TI  - Exhaled air temperature in asthmatic children: a mathematical evaluation.
AB  - Recently, the exhaled breath temperature has been proposed as a potential marker
      for the evaluation of airway inflammation in asthma. The purpose of this study
      was to verify the ability to distinguish asthmatics from normal controls by a
      dedicated detailed mathematical evaluation of the exhaled air curve. Analysis was
      performed in the different phases of the curve of exhaled temperature, i.e. the
      rate of temperature increase (Delta e degrees T) and the mean plateau value.
      Principal components analysis (PCA) and artificial neural networks (ANNs) were
      used for the evaluation of the data in 90 asthmatic children and in 33 healthy
      age-matched controls. Both PCA and ANNs showed that a separation between patients
      and controls can be obtained only by the evaluation of the plateau phase of the
      curve, which better reflects the periphery of the airway.

PMID- 18346099
TI  - Fast food consumption and increased caloric intake: a systematic review of a
      trajectory towards weight gain and obesity risk.
AB  - Consumption of fast food, which have high energy densities and glycemic loads,
      and expose customers to excessive portion sizes, may be greatly contributing to
      and escalating the rates of overweight and obesity in the USA. Whether an
      association exists between fast food consumption and weight gain is unclear.
      Sixteen studies (six cross sectional, seven prospective cohort, three
      experimental) meeting methodological and relevance criteria were selected for
      inclusion in this systematic review. While more research needs to be conducted
      specifically in regard to effects of fast food consumption among subpopulations
      such as children and adolescents, sufficient evidence exists for public health
      recommendations to limit fast food consumption and facilitate healthier menu
      selection. As the fast food industry continues to increase both domestically and
      abroad, the scientific findings and corresponding public health implications of
      the association between fast food consumption and weight are critical.

PMID- 18346100
TI  - Herbivore-induced shifts in carbon and nitrogen allocation in red oak seedlings.
AB  - * A dual-isotope, microcosm experiment was conducted with Quercus rubra (red oak)
      seedlings to test the hypothesis that foliar herbivory would increase belowground
      carbon allocation (BCA), carbon (C) rhizodeposition and nitrogen (N) uptake.
      Plant BCA links soil ecosystems to aboveground processes and can be affected by
      insect herbivores, though the extent of herbivore influences on BCA is not well
      understood in woody plants. * Microcosms containing 2-yr-old Q. rubra seedlings
      and soil collected from the Coweeta Hydrologic Laboratory (NC, USA) were
      subjected to herbivory or left as undamaged controls. All microcosms were then
      injected with 15N-glycine and pulsed with 13CO2. * Contrary to our hypothesis,
      herbivore damage reduced BCA to fine roots by 63% and correspondingly increased
      allocation of new C to foliage. However, 13C recoveries in soil pools were
      similar between treatments, suggesting that exudation of C from roots is an
      actively regulated component of BCA. Herbivore damage also reduced N allocation
      to fine roots by 39%, apparently in favor of storage in taproot and stem tissues.
      * Oak seedlings respond to moderate insect herbivore damage with a complex suite
      of allocation shifts that may simultaneously increase foliar C, maintain C
      rhizodeposition and N assimilation, and shift N resources to storage.

PMID- 18346101
TI  - Does leaf shedding increase the whole-plant carbon gain despite some nitrogen
      being lost with shedding?
AB  - When old leaves are shed, part of the nitrogen in the leaf is retranslocated to
      new leaves. This retranslocation will increase the whole-plant carbon gain when
      daily C gain : leaf N ratio (daily photosynthetic N-use efficiency, NUE) in the
      old leaf, expressed as a fraction of NUE in the new leaf, becomes lower than the
      fraction of leaf N that is resorbed before shedding (R(N)). We examined whether
      plants shed their leaves to increase the whole-plant C gain in accord with this
      criterion in a dense stand of an annual herb, Xanthium canadense, grown under
      high (HN) and low (LN) nitrogen availability. The NUE of a leaf at shedding
      expressed as a fraction of NUE in a new leaf was nearly equal to the R(N) in the
      LN stand, but significantly lower than the R(N) in the HN stand. Thus shedding of
      old leaves occurred as expected in the LN stand, whereas in the HN stand,
      shedding occurred later than expected. Sensitivity analyses showed that the
      decline in NUE of a leaf resulted primarily from a reduction in irradiance in the
      HN stand. On the other hand, it resulted from a reduction in irradiance and also
      in light-saturated photosynthesis : leaf N content ratio (potential
      photosynthetic NUE) in the LN stand.

PMID- 18346102
TI  - Coordinated expression of functionally diverse fructosyltransferase genes is
      associated with fructan accumulation in response to low temperature in perennial
      ryegrass.
AB  - * Fructan is the major nonstructural carbohydrate reserve in temperate grasses.
      To understand regulatory mechanisms in fructan synthesis and adaptation to cold
      environments, the isolation, functional characterization and genetic mapping of
      fructosyltransferase (FT) genes in perennial ryegrass (Lolium perenne) are
      described. * Six cDNAs (prft1-prft6) encoding FTs were isolated from cold-treated
      ryegrass plants, and three were positioned on a perennial ryegrass linkage map.
      Recombinant proteins were produced in Pichia pastoris and enzymatic activity was
      characterized. Changes in carbohydrate levels and mRNA levels of FT genes during
      cold treatment were also analysed. * One gene encodes sucrose-sucrose 1
      fructosyltransferase (1-SST), and two gene encode fructan-fructan 6G
      fructosyltransferase (6G-FFT). Protein sequences for the other genes (prfts 1, 2
      and 6) were similar to sucrose-fructan 6-fructosyltransferase (6-SFT). The 1-SST
      and prft1 genes were colocalized with an invertase gene on the ryegrass linkage
      map. The mRNA levels of prft1 and prft2 increased gradually during cold
      treatment, while those of the 1-SST and 6G-FFT genes first increased, but then
      decreased before increasing again during a longer period of cold treatment. *
      Thus at least two different patterns of gene expression have developed during the
      evolution of functionally diverse FT genes, which are associated in a coordinated
      way with fructan synthesis in a cold environment.

PMID- 18346103
TI  - Self/nonself perception and recognition mechanisms in plants: a comparison of
      self-incompatibility and innate immunity.
AB  - Analyses of emerging concepts indicate that parallels exist between self
      incompatibility and pathogen recognition. In the case of surveillance of
      'nonself', plant immune responses are triggered either by pattern recognition
      receptors (PRRs) that detect conserved pathogen-associated molecular patterns
      (PAMPs) or by resistance (R) proteins recognizing isolate-specific pathogen
      effectors. PAMP detection is an important component of innate immunity in plants
      and serves as an early warning system for the presence of potential pathogens and
      activation of plant defense mechanisms. In the Brassicaceae, the recognition of
      'self' and self-incompatibility are components of a receptor-ligand based
      mechanism that utilizes an S receptor kinase (SRK) to perceive and reject 'self'
      pollen. SRK is an S-domain receptor-like kinase (RLK), which in turn is part of
      the RLK family, some members of which represent PRRs involved in the detection of
      PAMPs. S-domain RLKs also occur in species that do not exhibit self
      incompatibility and are up-regulated in response to wounding, PAMPs and pathogen
      recognition. Although evolution may have driven expansion of certain RLK families
      to serve roles in particular physiological processes, this may not exclude these
      receptor types from functioning in different programs. Recent findings on
      self/nonself recognition are reviewed and conceptual and mechanistic links
      between microbial recognition and self-incompatibility are discussed.

PMID- 18346104
TI  - Flowering phenology in a species-rich temperate grassland is sensitive to warming
      but not elevated CO2.
AB  - * Flowering is a critical stage in plant life cycles, and changes might alter
      processes at the species, community and ecosystem levels. Therefore, likely
      flowering-time responses to global change drivers are needed for predictions of
      global change impacts on natural and managed ecosystems. * Here, the impact of
      elevated atmospheric CO2 concentration ([CO2]) (550 micromol mol(-1)) and warming
      (+2 masculineC) is reported on flowering times in a native, species-rich,
      temperate grassland in Tasmania, Australia in both 2004 and 2005. * Elevated
      [CO2] did not affect average time of first flowering in either year, only
      affecting three out of 23 species. Warming reduced time to first flowering by an
      average of 19.1 d in 2004, acting on most species, but did not significantly
      alter flowering time in 2005, which might be related to the timing of rainfall.
      Elevated [CO2] and warming treatments did not interact on flowering time. * These
      results show elevated [CO2] did not alter average flowering time or duration in
      this grassland; neither did it alter the response to warming. Therefore,
      flowering phenology appears insensitive to increasing [CO2] in this ecosystem,
      although the response to warming varies between years but can be strong.

PMID- 18346105
TI  - Apple shoot architecture: evidence for strong variability of bud size and
      composition and hydraulics within a branching zone.
AB  - * In the apple tree (Malus domestica), shoot architecture - the distribution of
      lateral bud types and growth along the parent shoot - has been extensively
      investigated. The distal zone of a shoot is characterized by a high proportion of
      vegetative or floral axillary branches mixed with latent buds and aborted
      laterals. The hypothesis tested here was that bud development was related to
      hydraulic conductance of the sap pathway to the bud, independently of an
      acrotonic (proximal vs distal) effect. * The distal zone of 1-yr-old shoots was
      studied on five cultivars for bud size and composition (number of appendages) and
      hydraulic conductance before bud burst. * Bud size, composition and hydraulic
      conductance were highly variable for all cultivars. A positive correlation was
      demonstrated between both the number of cataphylls and green-leaf primordia, and
      hydraulic conductance. Cultivar and bud size affected the intercept of these
      relationships more than the slope, suggesting similar scaling between these
      variables, but different hydraulic efficiencies. A great proportion of small buds
      were also characterized by null values of hydraulic conductance. * This study
      suggests that hydraulically mediated competition exists between adjacent buds
      within the same branching zone, prefiguring the variability of lateral types in
      the following growing season. It is hypothesized that this developmental
      patterning is driven by hydraulic characteristics of the whole metamer, including
      the subtending leaf, during bud development.

PMID- 18346106
TI  - Plant growth depressions in arbuscular mycorrhizal symbioses: not just caused by
      carbon drain?
AB  - * This study investigated effects of plant density and arbuscular mycorrhizal
      (AM) colonization on growth and phosphorus (P) nutrition of a cultivar of wheat
      (Triticum aestivum) that often shows early AM-induced growth depressions. * Two
      experiments were conducted. Expt 1 had three plant densities and one soil P
      concentration. Expt 2 had two plant densities and two P concentrations. Plants
      were grown in calcareous P-fixing soil, inoculated with Glomus intraradices or
      Gigaspora margarita, or noninoculated (nonmycorrhizal (NM)). Glomus intraradices
      colonized well and caused a growth depression only in Expt 1. Gigaspora margarita
      caused large growth depressions in both experiments even though it colonized
      poorly. * The results showed that growth depressions were mitigated by changes in
      relative competition for soil P by NM and AM plants, and probably by decreasing
      carbon costs of the fungi. * The different effects of the two fungi appear to be
      attributable to differences in the balance between P uptake by the fungal pathway
      and direct uptake via the roots. These differences may be important in other AM
      symbioses that result in growth depressions. The results show that mycorrhizal
      growth responses of plants grown singly may not apply at the population or
      community level.

PMID- 18346107
TI  - Biotic disturbance in expanding subarctic forests along the eastern coast of
      Hudson Bay.
AB  - * The past and present occurrence of insect disturbance on white spruce (Picea
      glauca) trees was evaluated at their northern range limit on the eastern coast of
      Hudson Bay, and its effects on tree growth and population dynamics studied. *
      Three sites were sampled along an altitudinal gradient. Ring-width chronologies
      and stem analysis were used to evaluate tree growth. The occurrence of holes in
      the bark, of resin pockets and blue-stain fungi, and ring-width evidence for
      growth releases were used to assess the impact of bark beetle. * The white spruce
      population was established at these sites in the 17th century. Since their
      establishment, the spruce trees have developed a tree growth form, except at the
      uppermost site, where severe growth suppression occurred in the 19th century.
      Bark beetle and blue-stain fungi occurred with different timing and intensity.
      Their highest occurrence, associated with high mortality rates, was at the lowest
      site in the late 20th century. In the uppermost sites, biotic disturbance has
      occurred since the 18th century, associated with evidence for mechanical
      disturbance. * The simultaneous arrival of white spruce in the area resulted in a
      synchronous onset of spruce beetle activity driven by tree ageing. Unfavourable
      climatic conditions affected tree growth severely in the most exposed sites.

PMID- 18346108
TI  - Identifying genetic components controlling fertility in the outcrossing grass
      species perennial ryegrass (Lolium perenne) by quantitative trait loci analysis
      and comparative genetics.
AB  - Mutational load and resource allocation factors and their effects on limiting
      seed set were investigated in ryegrass by comparative mapping genomics and
      quantitative trait loci (QTL) analysis in two perennial ryegrass (Lolium perenne)
      mapping families sharing common genetic markers. Quantitative trait loci for seed
      set were identified on chromosome (LG) 7 in both families and on LG4 of the
      F2/WSC family. On LG7, seed-set and heading date QTLs colocalized in both
      families and cannot be unequivocally resolved. Comparative genomics suggests that
      the LG7 region is syntenous to a region of rice LG6 which contains both fertility
      (S5(n)) and heading date (Hd1, Hd3a) candidate genes. The LG4 region is syntenous
      to a region of rice LG3 which contains a fertility (S33) candidate gene. QTL
      maxima for seed-set and heading date on LG4 in the F2/WSC family are separated by
      c. 8 cm, indicating distinct genetic control. Low seed set is under the control
      of recessive genes at both LG4 and LG7 locations. The identification of QTLs
      associated with seed set, a major component of seed yield in perennial ryegrass,
      indicates that mutational load associated with these genomic regions can be
      mitigated through marker-assisted selection.

PMID- 18346109
TI  - Nondestructive analysis of senescence in mesophyll cells by spectral resolution
      of protein synthesis-dependent pigment metabolism.
AB  - * Over 6 d of dark-induced senescence, leaf segments of wild-type Lolium
      temulentum lost > 96% chlorophyll a + b; leaves from plants containing a
      staygreen mutation introgressed from Festuca pratensis, which has a lesion in the
      senescence-associated fragmentation of pigment-proteolipid complexes, retained
      over 43% of total chlorophyll over the same period. * Mutant segments
      preferentially retained thylakoid membrane proteins (exemplified by LHCP II) but
      lost other cellular proteins at the same rate as wild-type tissue. The protein
      synthesis inhibitor D-MDMP inhibited chlorophyll degradation and partially
      prevented protein loss in both genotypes, but tissues treated with the
      ineffective L-stereoisomer were indistinguishable from water controls. *
      Principal-components analysis of leaf reflectance spectra distinguished between
      genotypes, time points and D-MDMP treatments, showing the disruption of pigment
      metabolism during senescence brought about by the staygreen mutation, by
      inhibition of protein synthesis and by combinations of the two factors. * The
      build-up of oxidized, dephytylated and phaeo-derivatives of chl a during
      senescence of staygreen tissue was prevented by D-MDMP and associated with
      characteristic difference spectra when senescent mutant tissue was compared with
      wild-type or inhibitor-treated samples. The suitability of senescence as a
      subject for systems biology approaches is discussed.

PMID- 18346110
TI  - Methoxyl groups of plant pectin as a precursor of atmospheric methane: evidence
      from deuterium labelling studies.
AB  - * The observation that plants produce methane (CH4) under aerobic conditions has
      caused considerable controversy among the scientific community and the general
      public. It led to much discussion and debate not only about its contribution to
      the global CH4 budget but also about the authenticity of the observation itself.
      Previous results suggested that methoxyl groups of the abundant plant structural
      component pectin might play a key role in the in situ formation process of CH4.
      Here, this effect is investigated using an isotope labelling study. *
      Polysaccharides, pectin and polygalacturonic acid, with varying degrees of
      trideuterium-labelled methyl groups in the methoxyl moieties, were investigated
      for CH4 formation under UV irradiation and heating. * A strong deuterium signal
      in the emitted CH4 was observed from these labelled polysaccharides. * Results
      clearly demonstrate that ester methyl groups of pectin can serve as a precursor
      of CH4, supporting the idea of a novel chemical route of CH4 formation in plants
      under oxic environmental conditions.

PMID- 18346111
TI  - Tomato strigolactones are derived from carotenoids and their biosynthesis is
      promoted by phosphate starvation.
AB  - * Strigolactones are rhizosphere signalling compounds that mediate host location
      in arbuscular mycorrhizal (AM) fungi and parasitic plants. Here, the regulation
      of the biosynthesis of strigolactones is studied in tomato (Solanum
      lycopersicum). * Strigolactone production under phosphate starvation, in the
      presence of the carotenoid biosynthesis inhibitor fluridone and in the abscisic
      acid (ABA) mutant notabilis were assessed using a germination bioassay with seeds
      of Orobanche ramosa; a hyphal branching assay with Gigaspora spp; and by liquid
      chromatography coupled to tandem mass spectrometry (LC-MS/MS) analysis. * The
      root exudates of tomato cv. MoneyMaker induced O. ramosa seed germination and
      hyphal branching in AM fungi. Phosphate starvation markedly increased, and
      fluridone strongly decreased, this activity. Exudates of notabilis induced
      approx. 40% less germination than the wild-type. The LC-MS/MS analysis confirmed
      that the biological activity and changes therein were due to the presence of
      several strigolactones; orobanchol, solanacol and two or three didehydro
      orobanchol isomers. * These results show that the AM branching factors and
      parasitic plant germination stimulants in tomato root exudate are strigolactones
      and that they are biosynthetically derived from carotenoids. The dual activity of
      these signalling compounds in attracting beneficial AM fungi and detrimental
      parasitic plants is further strengthened by environmental conditions such as
      phosphate availability.

PMID- 18346112
TI  - Vernalization-induced repression of FLOWERING LOCUS C stimulates flowering in
      Sinapis alba and enhances plant responsiveness to photoperiod.
AB  - * Of the Brassicaceae, Sinapis alba has been intensively studied as a
      physiological model of induction of flowering by a single long day (LD), while
      molecular-genetic analyses of Arabidopsis thaliana have disclosed complex
      interactions between pathways controlling flowering in response to different
      environmental cues, such as photoperiod and vernalization. The vernalization
      process in S. alba was therefore analysed here. * The coding sequence of S. alba
      SaFLC, which is orthologous to the A. thaliana floral repressor FLOWERING LOCUS
      C, was isolated and the transcript levels quantified in different conditions. *
      Two-week-old seedlings grown in noninductive short days (SDs) were vernalized for
      1-6 wk. Down-regulation of SaFLC was already marked after 1 wk of cold but 2 wk
      was needed for a significant acceleration of flowering. Flower buds were
      initiated during vernalization. When vernalization was stopped after 1 wk,
      repression of SaFLC was not stable but a significant increase in plant
      responsiveness to 16-h LDs was observed when LDs followed immediately after the
      cold treatment. * These results suggest that vernalization does not only work
      when plants experience long exposure to cold during the winter: shorter cold
      periods might stimulate flowering of LD plants if they occur when photoperiod is
      increasing, such as in spring.

PMID- 18346113
TI  - Stem cell protein BMI-1 is an independent marker for poor prognosis in
      oligodendroglial tumours.
AB  - AIMS: The polycomb factor BMI-1 has recently been implicated in tumorigenesis of
      the central nervous system in several experimental animal models. However, the
      significance of BMI-1 in human glioma has not been investigated. Here we describe
      expression of the polycomb protein BMI-1 and its downstream targets p16(Ink4a)
      and MDM2 in both high- and low-grade human glioma. METHODS: Tumour samples were
      collected from 305 adult patients treated for primary grades 2-4 gliomas between
      1980 and 2006 in Finland and Germany. BMI-1, p16 and MDM2 expression was
      evaluated using immunohistochemistry in representative paraffin-embedded tumour
      tissue. The significance of observed immunoreactivity, age at onset, gender,
      histopathological findings and proliferative index was analysed in univariate and
      multivariate survival models. RESULTS: BMI-1 was expressed in all histologic
      types of diffuse gliomas. We found a significant correlation (P = 0.007) between
      the frequency of BMI-1 immunoreactive tumour cells and poor survival in World
      Health Organization grades II-III oligodendrogliomas and oligoastrocytomas (n =
      62). The median survival of patients grouped by low, intermediate or high
      frequency of BMI-1 immunoreactive tumour cells was 191 months, 151 months and 68
      months, respectively. This association was also significant in the Cox
      multivariate regression model. Nuclear p16 immunopositivity predicted better
      survival in astrocytomas and an inverse correlation between p16 expression and
      the Ki-67 mitotic index was also observed. CONCLUSIONS: BMI-1 is found in all
      histological types of gliomas and the relative protein expression of BMI-1 is a
      novel independent prognostic marker in oligodendroglial tumours.

PMID- 18346114
TI  - Beta-amyloid deposition in brains of subjects with diabetes.
AB  - AIM: A causative association between diabetes mellitus (DM) and Alzheimer's
      disease (AD) has been suggested based on clinical and epidemiological studies.
      One hypothesis is that the link between DM and AD is related to the function of
      insulin-degrading enzyme (IDE), an enzyme that degrades not only insulin and
      pancreatic amylin but also beta-amyloid (Abeta). Thus, in diabetics, insulin and
      Abeta might compete for IDE and this might lead to an increase in Abeta. The
      objective of this study was to test the hypothesis that hyperinsulinaemia can
      elevate Abeta levels and thus contribute to AD pathology in humans. METHODS:
      Neuropathological examination was carried out employing conventional and
      immunohistochemical (IHC) methods of the brains obtained post mortem from 701
      aged subjects. RESULTS: The loads of IHC/Abeta, silver stained neuritic plaques
      (NP) and neurofibrillary tangles (NFT) were significantly higher in subjects
      carrying the Apolipoprotein E e4 allele. In contrast, the loads of Abeta, NPs and
      NFT in the brains were not influenced by hyperglycaemia when comparing 134
      diabetic with 567 non-diabetic subjects. CONCLUSIONS: We conclude that the
      hypothesis that hyperinsulinaemia would significantly elevate the Abeta load and
      thus increase the extent of AD pathology cannot be supported. Our result
      challenges the claim that DM is a direct risk factor of developing AD. Thus
      further studies on pathological lesions in demented diabetics should be
      conducted.

PMID- 18346115
TI  - Spinal anterior horn cells in sporadic amyotrophic lateral sclerosis show
      ribosomal detachment from, and cisternal distention of the rough endoplasmic
      reticulum.
AB  - AIMS: Sporadic amyotrophic lateral sclerosis (ALS) is a progressive and
      invariably fatal disease involving the upper and lower motor neurones of adult
      humans. Among the neuropathological features of the disease, abnormalities in the
      protein-synthesizing system in motor neurones of the brainstem and spinal cord,
      such as a decrease of cytoplasmic RNA and rough endoplasmic reticulum (rER)
      (chromatolysis), defective editing of the Q/R site of the glutamate receptor
      subunit GluR2 mRNA, fragmentation of the Golgi apparatus and accumulation of
      ubiquitinated inclusions and abnormal TdP-43 protein have been reported to be
      essential for the degeneration. In relation to these features, although the
      possibility of ER stress has been reported in motor neurones of the brainstem and
      spinal cord of ALS patients, the rER itself has not been a main target of
      ultrastructural investigation. METHODS: The present study examined the rER,
      ultrastructurally and quantitatively in the spinal anterior horn cells (AHCs) of
      21 Japanese patients with sporadic ALS and eight Japanese control subjects.
      RESULTS AND CONCLUSIONS: It was found that: (i) the rER cisternae in AHCs showing
      central chromatolysis were fragmented, but retained their width and had normally
      attached ribosomes, and (ii) the rER cisternae in shrunken AHCs were irregularly
      distended with detachment of the ribosomes, thus suggesting that (iii) ribosomal
      detachment was related to rER distention.

PMID- 18346116
TI  - Inverse transcriptional activities during complementary chromatic adaptation are
      controlled by the response regulator RcaC binding to red and green light
      responsive promoters.
AB  - Complementary chromatic adaptation (CCA) provides cyanobacteria with the ability
      to shift between red and blue-green phenotypes that are optimized for absorption
      of different wavelengths of light. Controlled by the ratio of green to red light,
      this process results from differential expression of two groups of operons, many
      of which encode proteins involved in photosynthetic light harvesting antennae
      biogenesis. In the freshwater species Fremyella diplosiphon, the inverse
      regulation of these two classes is complex and occurs through different
      mechanisms. It also involves a two-component pathway that includes a phytochrome
      class photoreceptor and the response regulator RcaC. Here we uncover the
      mechanism through which this system controls CCA by demonstrating that RcaC binds
      to the L Box within promoters of both classes of light-regulated operons. We
      provide functional evidence that complementary regulation of these operons occurs
      by RcaC's simultaneous activation and repression of transcription in red light.
      We identify rcaC and L Boxes in the genome of a marine cyanobacterium capable of
      CCA, suggesting widespread use of this control system. These results provide
      important insights into the long-standing enigma of CCA regulation and complete
      the first description of an entire two-component system controlled by a
      phytochrome-class photoreceptor.

PMID- 18346117
TI  - The role of Candida albicans FAR1 in regulation of pheromone-mediated mating,
      gene expression and cell cycle arrest.
AB  - Candida albicans cells homozygous for the MTLa locus respond to alpha-mating
      pheromone by activating gene expression and triggering morphological changes, and
      the cells undergo a pheromone-mediated cell cycle arrest that can be influenced
      by nutritional conditions. Disruption of C. albicans ORF19.7105, which is the
      predicted homologue of the yeast FAR1 gene, blocks pheromone-mediated
      morphological changes, prevents pheromone-mediated cell cycle arrest, greatly
      compromises mating and also blocks pheromone-triggered gene induction. C.
      albicans ORF19.7105 is not pheromone inducible, but overexpression of this gene
      from the actin promoter greatly enhances pheromone-mediated cell cycle arrest,
      leading to clear halos in growth inhibition assays on a variety of solid media.
      Transcriptional profiling of the ORF19.7105-overexpressing strain has established
      an enhanced responsiveness of pheromone-induced genes. Thus the C. albicans FAR1
      gene is a dosage-dependent regulator of the pheromone response, and is critically
      required for all aspects of mating process of this pathogenic fungus.

PMID- 18346118
TI  - Have rural background students been disadvantaged by the medical school admission
      process?
AB  - CONTEXT: The proportion of rural background applicants to medical school does not
      reflect the proportion of the general population that resides in rural
      communities. It is also believed that rural background applicants are
      disadvantaged by the admission processes of urban-based medical schools. This
      study sought to examine how rural background applicants actually fare as they
      progress through the stages of admission. METHODS: A 10-year cohort of Alberta
      applicants were tracked as they progressed through the interview and admittance
      stages. Background, grade point averages (GPAs) and Medical College Admission
      Test (MCAT) scores plus interview ratings were utilised in the analysis. RESULTS:
      Of the 4407 applicants, 1138 were interviewed. Significantly greater proportions
      of urban (26.8%) and rural (29.1%) background applicants than regional background
      (21.0%) applicants were interviewed, although the GPAs and MCAT scores of
      regional background applicants did not differ from those of the other applicant
      groups. Of those interviewed, 463 applicants were admitted. The proportions of
      urban (39.9%), regional (42.3%) and rural (46.3%) background applicants admitted
      were similar. Reviewers did not rate the files of urban, regional and rural
      background applicants differently. Only 6.7% of applicants admitted had rural
      backgrounds. DISCUSSION: Rural background applicants were not disadvantaged or
      discriminated against by the admission process. Although the backgrounds of
      applicants admitted reflect those of the original applicants, the proportion of
      rural background applicants is below the proportion of Albertans who reside in
      rural areas. Strategies to increase the number of applicants of rural origin are
      recommended.

PMID- 18346119
TI  - Sexual harassment during clinical clerkships in Dutch medical schools.
AB  - CONTEXT: Sexual harassment of medical students has been the focus of many
      international studies. Prevalence rates from 18% to over 60% have been reported.
      However, a Dutch study at Nijmegen Medical School found the prevalence rate to be
      lower (13.3% in the total group; 20% among female students only). OBJECTIVES: We
      aimed to identify whether Nijmegen constitutes a positive sample of Dutch medical
      schools or whether incidents of sexual harassment are less prevalent in the
      Netherlands than elsewhere, and to establish if and how these experiences impact
      the professional lives of students. METHODS: Students received a semi-structured
      questionnaire containing questions about their experiences of sexual harassment
      during clerkships. The questions referred to students' reactions to any
      incidents, the possible consequences for their wellbeing or professional
      functioning and the way cases of sexual harassment were handled. RESULTS: The
      prevalence of sexual harassment was significantly higher in Utrecht than in
      Nijmegen. In both studies rates were relatively low compared with international
      data. Nevertheless, 1 in 3-5 Dutch female medical students had experienced
      unwelcome sexual attention from patients, colleagues or supervisors. Three of 10
      students who had experienced such an incident stated that it had a negative
      impact on their functioning afterwards. CONCLUSIONS: Prevalence rates of sexual
      harassment in medical schools in the Netherlands are low compared with
      international rates. However, the number of women students who experience sexual
      harassment is still 1 in 3-5. The occurrence of and ways to deal with these
      incidents should be important topics in the training of medical students and
      supervisors.

PMID- 18346120
TI  - Validity of the visual analogue scale as an instrument to measure self-efficacy
      in resuscitation skills.
AB  - CONTEXT: Self-efficacy is an important factor in many areas of medical education,
      including self-assessment and self-directed learning, but has been little studied
      in resuscitation training, possibly because of the lack of a simple measurement
      instrument. OBJECTIVE: We aimed to assess the validity of a visual analogue scale
      (VAS) linked to a single question as an instrument to measure self-efficacy with
      respect to resuscitation skills by comparing the VAS with a questionnaire and
      using known-groups comparisons. METHODS: We developed questionnaires to measure
      self-efficacy for a number of resuscitation tasks and for computer skills. These
      were compared with VASs linked to a single question per task, using a multi
      trait, multi-method matrix. We also used known-groups comparisons of self
      efficacy in specific professional groups. RESULTS: There was good correlation
      between the questionnaires and the VASs for self-efficacy for specific
      resuscitation tasks. There was a less clear correlation for self-efficacy for
      paediatric resuscitation overall. There was no correlation between self-efficacy
      for resuscitation and computer tasks. In specific professional groups, measured
      self-efficacy accorded with theoretical predictions. CONCLUSIONS: A VAS linked to
      a single question appears to be a valid method of measuring self-efficacy with
      respect to specific well defined resuscitation tasks, but should be used with
      caution for multi-faceted tasks.

PMID- 18346121
TI  - Nested clade analysis: an extensively validated method for strong phylogeographic
      inference.

PMID- 18346122
TI  - Age at maturity in wild baboons: genetic, environmental and demographic
      influences.
AB  - The timing of early life-history events, such as sexual maturation and first
      reproduction, can greatly influence variation in individual fitness. In this
      study, we analysed possible sources of variation underlying different measures of
      age at social and physical maturation in wild baboons in the Amboseli basin,
      Kenya. The Amboseli baboons are a natural population primarily comprised of
      yellow baboons (Papio cynocephalus) that occasionally hybridize with anubis
      baboons (Papio anubis) from outside the basin. We found that males and females
      differed in the extent to which various factors influenced their maturation.
      Surprisingly, we found that male maturation was most strongly related to the
      proportion of anubis ancestry revealed by their microsatellite genotypes: hybrid
      males matured earlier than yellow males. In contrast, although hybrid females
      reached menarche slightly earlier than yellow females, maternal rank and the
      presence of maternal relatives had the largest effects on female maturation,
      followed by more modest effects of group size and rainfall. Our results indicate
      that a complex combination of demographic, genetic, environmental, and maternal
      effects contribute to variation in the timing of these life-history milestones.

PMID- 18346123
TI  - A phylogeographical analysis of the range disjunction for foxtail pine (Pinus
      balfouriana, Pinaceae): the role of Pleistocene glaciation.
AB  - Biogeographical patterns within the California Floristic Province have been
      greatly affected by geological and climatic events. Here, we investigate the
      phylogeography of foxtail pine (Pinus balfouriana) in an effort to date its range
      disjunction using molecular data and to further our understanding of
      phylogeographical patterns for plants within the California Floristic Province.
      The distribution of foxtail pine is characterized by a 500-km disjunction
      separating populations located in the Klamath Mountains from those in the
      southern Sierra Nevada. Previous authors suggested that this disjunction occurred
      approximately 4000-8000 years ago during the Holocene Xerotherm when western
      North America became warmer and drier. Those dates, however, are inconsistent
      with the morphological differences that separate regional populations into
      formally recognized subspecies. Using the coalescent-based isolation with
      migration model and DNA sequence data from the chloroplast, mitochondrial, and
      nuclear genomes, we evaluate several hypotheses addressing the timing of this
      range disjunction and its effects on subsequent patterns of gene flow. Results
      from all three genomes are largely consistent with Middle to Early Pleistocene
      divergence dates. Those dates correspond to the Sherwin glaciation, which was the
      largest Pleistocene glacial episode in the Sierra Nevada. Gene flow, moreover,
      was only documented using data from the chloroplast genome, suggesting that low
      levels of long-distance pollen dispersal (N(e)m < 0.5) have occurred since this
      divergence event. These results are extended to a discussion of the
      biogeographical development of subalpine forests in California.

PMID- 18346124
TI  - Genetic consequences of natal dispersal in the colonial lesser kestrel.
AB  - Dispersal is a life-history trait that plays a fundamental role in population
      dynamics, influencing evolution, species distribution, and the genetics and
      structure of populations. In spite of the fact that dispersal has been
      hypothesized to be an efficient behavioural mechanism to avoid inbreeding, the
      expected relationship between dispersal and mate relatedness still remains
      controversial. Here, we examine the genetic consequences of natal dispersal,
      namely the higher chance of obtaining genetically less similar mates as a result
      of moving from natal to breeding sites, in a lesser kestrel (Falco naumanni)
      population. Relatedness between individuals tended to decrease with distance
      between their breeding colonies, indicating that the study population follows an
      'isolation-by-distance' pattern of spatial genetic structure. Such a fine-scale
      genetic structure generates a scenario in which individuals can potentially
      increase the chance of obtaining genetically less similar mates by dispersing
      over larger distances from their natal colony. Using dispersal information and
      genotypic data, we showed that mate relatedness decreased with natal dispersal
      distance, an effect that remained significant both while including and excluding
      philopatric individuals from the data set. These results, together with the well
      known detrimental consequences of reduced genetic diversity in the study
      population, suggest that dispersal may have evolved, at least in part, to avoid
      the negative fitness consequences of mating with genetically similar individuals.

PMID- 18346125
TI  - Genetic impoverishment of the last black grouse (Tetrao tetrix) population in the
      Netherlands: detectable only with a reference from the past.
AB  - We have studied a small isolated population of black grouse (Tetrao tetrix) in
      the Netherlands to examine the impact of isolation and reduction in numbers on
      genetic diversity. We compared the genetic diversity in the last extant Dutch
      population with Dutch museum samples and three other black grouse populations
      (from England, Austria and Norway, respectively) representing isolated and
      continuous populations. We found significantly lower allelic richness, observed
      and expected heterozygosities in the present Dutch population compared to the
      continuous populations (Austria and Norway) and also to the historical Dutch
      population. However, using a bottleneck test on each population, signs of
      heterozygosity excess were only found in the likewise isolated English population
      despite that strong genetic drift was evident in the present Dutch population in
      comparison to the reference populations, as assessed both in pairwise F(ST)and
      STRUCTURE analyses. Simulating the effect of a population reduction on the Dutch
      population from 1948 onwards, using census data and with the Dutch museum samples
      as a model for the genetic diversity in the initial population, revealed that the
      loss in number of alleles and observed heterozygosity was according to genetic
      drift expectations and within the standard error range of the present Dutch
      population. Thus, the effect of the strong decline in the number of grouse on
      genetic diversity was only detectable when using a reference from the past. The
      lack of evidence for a population reduction in the present Dutch population by
      using the program bottleneck was attributed to a rapidly found new equilibrium as
      a consequence of a very small effective population size.

PMID- 18346126
TI  - Pinpointing a selective sweep to the chimpanzee MHC class I region by comparative
      genomics.
AB  - Chimpanzees experienced a reduction of the allelic repertoire at the major
      histocompatibility complex (MHC) class I A and B loci, which may have been caused
      by a retrovirus belonging to the simian immunodeficiency virus (SIV) family.
      Extended MHC haplotypes were defined in a pedigreed chimpanzee colony. Comparison
      of genetic variation at microsatellite markers mapping inside and outside the Mhc
      region was carried out in humans and chimpanzees to investigate the genomic
      extent of the repertoire reduction. Multilocus demographic analyses underscored
      that chimpanzees indeed experienced a selective sweep that mainly targeted the
      chromosomal segment carrying the Mhc class I region. Probably due to genetic
      linkage, the sweep also affected other polymorphic loci, mapping in the close
      vicinity of the Mhc class I region genes. Nevertheless, although the allelic
      repertoire at particular Mhc class I and II loci appears to be limited, naturally
      occurring recombination events allowed the establishment of haplotype diversity
      after the sweep. However, recombination did not have sufficient time to erase the
      signal of the selective sweep.

PMID- 18346127
TI  - Haplotype reconstruction for scnp DNA: a consensus vote approach with extensive
      sequence data from populations of the migratory locust (Locusta migratoria).
AB  - Single copy nuclear polymorphic (scnp) DNA is potentially a powerful molecular
      marker for evolutionary studies of populations. However, a practical obstacle to
      its employment is the general problem of haplotype determination due to the
      common occurrence of heterozygosity in diploid organisms. We explore here a
      'consensus vote' (CV) approach to this question, combining statistical haplotype
      reconstruction and experimental verification using as an example an indel-free
      scnp DNA marker from the flanking region of a microsatellite locus of the
      migratory locust. The raw data comprise 251-bp sequences from 526 locust
      individuals (1052 chromosomes), with 71 (28.3%) polymorphic nucleotide sites
      (including seven triallelic sites) and 141 distinct genotypes (with frequencies
      ranging from 0.2 to 25.5%). Six representative statistical haplotype
      reconstruction algorithms are employed in our CV approach, including one
      parsimony method, two expectation-maximization (EM) methods and three Bayesian
      methods. The phases of 116 ambiguous individuals inferred by this approach are
      verified by molecular cloning experiments. We demonstrate the effectiveness of
      the CV approach compared to inferences based on individual statistical
      algorithms. First, it has the unique power to partition the inferrals into a
      reliable group and an uncertain group, thereby allowing the identification of the
      inferrals with greater uncertainty (12.7% of the total sample in this case). This
      considerably reduces subsequent efforts of experimental verification. Second,
      this approach is capable of handling genotype data pooled from many geographical
      populations, thus tolerating heterogeneity of genetic diversity among
      populations. Third, the performance of the CV approach is not influenced by the
      number of heterozygous sites in the ambiguous genotypes. Therefore, the CV
      approach is potentially a reliable strategy for effective haplotype determination
      of nuclear DNA markers. Our results also show that rare variations and rare
      inferrals tend to be more vulnerable to inference error, and hence deserve extra
      surveillance.

PMID- 18346128
TI  - Good species despite massive hybridization: genetic research on the contact zone
      between the watersnakes Nerodia sipedon and N. fasciata in the Carolinas, USA.
AB  - Genomic markers generated with the amplified fragment length polymorphism method
      revealed extensive, panmictic-like hybridization along the narrow contact zone
      between the water snakes Nerodia sipedon and Nerodia fasciata in the Carolinas,
      USA. However, asymmetric distributions of diagnostic markers between both species
      and low frequencies of backcrossed hybrids with a high value of interspecific
      mixture infer selection against certain genotypes. This is consistent with a
      pronounced genetic and morphological preponderance of N. fasciata characters in
      the hybrid zone. Despite massive hybridization within the contact zone, the
      existence of nearly fixed genetic markers and the potential inferiority of
      certain hybrid genotypes support the species status of the two taxa and
      corroborate known, but nondiagnostic differences in morphology and ecology. This
      study stretches the applicability of species concepts to cases, where the genetic
      compatibility between two closely related species is very high, yet, they still
      evolve and persist as independent entities.

PMID- 18346129
TI  - Natural history and prognostic factors of primary biliary cirrhosis in Taiwan: a
      follow-up study up to 18 years.
AB  - PURPOSE: The natural history of primary biliary cirrhosis (PBC) has been little
      studied in Asia. We conducted a Taiwanese cohort study on the natural history of
      PBC and analysed the prognostic factors. METHODS: This study enrolled 96
      consecutive PBC patients between 1985 and 2006 to evaluate the baseline
      characteristics and outcomes. RESULTS: There were 74 females and 22 males. Eighty
      five were positive for antimitochondrial antibodies in sera, and 11 were
      negative. The clinical manifestations and prognosis were similar between these
      two groups. In a median follow-up of 47.5+/-55.8 months, 27 patients died.
      Multivariate analysis indicated that the independent prognostic factors were
      serum albumin (P=0.021), creatinine (P=0.033) and ursodeoxycholic acid treatment
      (P=0.008). Besides, 42 patients developed adverse outcomes. Albumin (P<0.001),
      bilirubin (P=0.019) and prothrombin time (PT) (P=0.010) were significant factors.
      Moreover, a Mayo risk score <5, a Model for End-Stage Liver Disease (MELD) score
      <6, a Child-Pugh stage A and early liver histology were associated with
      favourable outcomes. CONCLUSION: Serum albumin, bilirubin and PT were independent
      prognostic factors of adverse outcomes for Taiwanese PBC patients. Besides, the
      Mayo risk score, the MELD score, the Child-Pugh stage and liver histology were
      also validated to predict survival.

PMID- 18346130
TI  - Sialoadenectomy enhances hepatic injury induced by
      lipopolysaccharide/galactosamine in mice.
AB  - BACKGROUND: Submandibular salivary glands (SMGs) synthesize, accumulate and
      secrete a large amount of epidermal growth factor (EGF) in mice. It is known that
      surgical removal of SMG (sialoadenectomy) alters cell turnover in the liver and
      exacerbates liver injury induced by lipopolysaccharide/galactosamine (LPS/GalN).
      RESULTS: Here we show that such increased hepatotoxicity is not the consequence
      of the lack of EGF production from SMG. On the contrary, it appears to be the
      consequence of an inadequate cytokine production by the liver of
      sialoadenectomized mice. Thus, we found that the increase of plasma tumour
      necrosis factor-alpha and interleukin-6 was slower in sialoadenectomized than in
      sham-operated mice. This is because of a decreased rate of production of both
      cytokines by the liver. We found that the increase of plasma corticosterone (CS)
      concentration is lower in sialoadenectomized than that in sham-operated mice.
      Adrenalectomy exacerbated liver injury induced by LPS/GalN. In these animals,
      sialoadenectomy did not further increase the effect of LPS/GalN. CONCLUSIONS: Our
      results suggest that the effect of sialoadenectomy on LPS/GalN-induced liver
      toxicity may be the consequence of an altered cytokine production by the liver
      and a reduced CS release from adrenal glands.

PMID- 18346131
TI  - Macaca radiata (bonnet monkey): a spontaneous model of nonalcoholic fatty liver
      disease.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a well-recognized
      condition that includes a spectrum of clinicopathology conditions ranging from
      steatotosis to cirrhosis and liver failure. Available animal models are not ideal
      as they show only a partial resemblance to characteristic human NAFLD. OBJECTIVE:
      This study was aimed at identifying a nonhuman primate model of NAFLD resembling
      features of human NAFLD, which will be useful in understanding the mechanism of
      the onset of this disease and for developing novel therapeutic modalities.
      METHODS: The histological status of the liver and serum levels of triglycerides
      (TG), cholesterol, aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT) of aged bonnet monkeys were compared with that of the aged rhesus and adult
      bonnet monkeys. Histopathology and immunostaining of liver sections and oil red
      'O' confirmed NAFLD in aged bonnet monkeys. RESULTS: Aged bonnet monkeys showed a
      significant (P<0.01) increase in serum TG, AST and ALT compared with aged rhesus
      and adult bonnet monkeys. Histopathology of the liver of aged bonnet macaques
      showed diffused microvesicular and macrovesicular fatty changes, perivenular and
      portal and perisinusoidal fibrosis with fatty degeneration of hepatocytes, and
      immunostaining of liver sections was suggestive of NAFLD. CONCLUSION: The
      spontaneous occurrence of NAFLD in normal animals is rare, but aged bonnet
      monkeys may serve as a unique animal model for studies related to NAFLD because
      they mimic pathophysiological features of human NAFLD.

PMID- 18346132
TI  - Chemopreventive effect of selenium and Chinese medicinal herbs on N-nitrosobis(2
      oxopropyl)amine-induced hepatocellular carcinoma in Syrian hamsters.
AB  - BACKGROUND/AIMS: Oxidative DNA damage by reactive oxygen species is involved in
      the process of liver carcinogenesis. To test the hypothesis that a remedy
      containing Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium
      Willd (Bs) (Sb/Bs remedy) modulates hepatic neoplastic growth, BOP (N
      nitrosobis(2-oxopropyl)amine)-induced liver cancers in hamsters were established.
      METHODS: Parameters such as survival rate, tumour area, tumour foci, 8
      hydroxydeoxyguanosine (8-OHdG), caspase-3, transforming growth factor (TGF-beta1)
      and tumour necrosis factor-alpha (TNF-alpha) were measured after Sb/Bs remedy
      treatment during BOP-induced carcinogenesis. RESULTS: The results showed that the
      Sb/Bs remedy and its constituents Sb and Bs suppressed the tumour area in BOP
      induced liver tumours. Because selenium (Sel) is toxic at a high dose (10 mg/kg),
      with a low survival rate (0%), the combination of Sb/Bs remedy and low-dose Sel
      (1 mg/kg) was found to decrease the tumour area and the number of tumour foci
      while increasing serum TNF-alpha and TGF-beta1, but not IL-6 levels. Besides, the
      Sb/Bs remedy, when combined with low-dose Sel, not only decreased the expression
      of 8-OHdG and increased caspase-3 expression within the glutathione S-transferase
      placental form-positive tumour foci but also increased tumour apoptosis in BOP
      induced hamsters. CONCLUSIONS: We conclude that low-dose Sel has a
      chemoprevention effect on BOP-induced liver tumours and such an effect was more
      enhanced when combined with Sb/Bs treatment.

PMID- 18346133
TI  - Nuclear factor-kappaB inhibition improves myocardial contractility in rats with
      cirrhotic cardiomyopathy.
AB  - BACKGROUND/AIMS: Cytokines such as tumour necrosis factor (TNF-alpha) contribute
      to the pathogenesis of cirrhotic cardiomyopathy. Nuclear factor-kappaB (NF
      kappaB) is crucial for cytokine regulation, and induces cardiac dysfunction in
      several heart disease models. We aimed to elucidate possible NF-kappaB
      involvement in cirrhotic cardiomyopathy. METHODS: Rats were bile duct ligated
      (BDL) to produce cirrhosis; controls received sham operation. Animals were
      studied 4 weeks later. Two NF-kappaB inhibitors were used: pyrrolidine
      dithiocarbamate (PDTC) and Bay 11-7082. Four groups were studied in most
      protocols: sham control, sham+PDTC, BDL and BDL+PDTC. Additional contractility
      studies were performed with Bay 11-7082. Myocardial NF-kappaB and TNF-alpha
      expression was measured by Western blot and ELISA. The contractility of isolated
      cardiomyocytes was observed under direct microscopy. RESULTS: Nuclear factor
      kappaB and TNF-alpha levels were increased in cirrhotic hearts compared with
      controls. PDTC significantly reduced NF-kappaB activity and TNF-alpha expression
      in cirrhotic hearts; controls were unaffected. Cirrhotic cardiomyocytes showed
      decreased systolic and diatolic velocity compared with sham controls. Both PDTC
      and Bay 11-7082 restored contractile function in cirrhotic cardiomyocytes, but
      did not affect controls. CONCLUSIONS: Inhibition of the increased NF-kappaB
      activity in cirrhotic hearts was associated with improvement of attenuated
      cardiomyocyte contractility. NF-kappaB, via effects on cytokine expression, may
      contribute to the pathogenesis of cirrhotic cardiomyopathy.

PMID- 18346134
TI  - A highly efficient gene-targeting system for Aspergillus parasiticus.
AB  - AIMS: To establish a system that greatly increases the gene-targeting frequency
      in Aspergillus parasiticus. METHODS AND RESULTS: The ku70 gene, a gene of the
      nonhomologous end-joining (NHEJ) pathway, was replaced by the nitrate reductase
      gene (niaD) in A. parasiticus RHN1 that accumulates O-methylsterigmatocystin
      (OMST). The NHEJ-deficient strain, RHDeltaku70, produced conidia, sclerotia and
      OMST normally. It had identical sensitivity as RHN1 to the DNA-topoisomerase I
      complex inhibitor, camptothecin, and the DNA-damaging agent, melphalan. For
      targeting an aflatoxin biosynthetic pathway gene, adhA, partial restriction
      enzyme recognition sequences in its flanking regions were manipulated to create
      homologous ends for integration. Using a linearized DNA fragment that contained
      Aspergillus oryzae pyrithiamine resistance gene (ptr) marker the adhA-targeting
      frequency in RHDeltaku70 reached 96%. CONCLUSIONS: The homologous recombination
      pathway is primarily responsible for repair of DNA damages in A. parasiticus. The
      NHEJ-deficient RHDeltaku70, easy creation of homologous ends for integration, and
      the ptr-based selection form a highly efficient gene-targeting system. It
      substantially reduces the time and workload necessary to obtain knockout strains
      for functional studies. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed
      system not only streamlines targeted gene replacement and disruption but also can
      be used to target specific chromosomal locations like promoters or intergenic
      regions. It will expedite the progresses in the functional genomic studies of A.
      parasiticus and Aspergilllus flavus.

PMID- 18346135
TI  - Extraction of DNA from soil using nanoparticles by magnetic bioseparation.
AB  - AIMS: To develop a simple, rapid and inexpensive soil DNA extraction protocol.
      METHODS AND RESULTS: The protocol relies on the use of superparamagnetic silica
      magnetite nanoparticles for the isolation and purification of DNA from soil
      samples. DNA suitable for use in molecular biology applications was obtained from
      a number of soil samples. CONCLUSIONS: The DNA extracted using the tested method
      successfully permitted the PCR amplification of a fragment of the bacterial 16S
      rDNA gene. The extracted DNA could also be restriction endonuclease digested.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The protocol reported here is simple and
      permits rapid isolation of PCR-ready soil DNA. The method requires only small
      quantities of soil sample, is scalable and suitable for automation.

PMID- 18346136
TI  - Detection of Salmonella enterica in food using two-step enrichment and real-time
      polymerase chain reaction.
AB  - AIMS: A new real-time polymerase chain reaction-based method was developed for
      the detection of Salmonella enterica in food. METHODS AND RESULTS: The method
      consisted of a novel two-step enrichment involving overnight incubation in
      buffered peptone water and a 5-h subculture in Rappaport-Vassiliadis medium,
      lysis of bacterial cells and a Salmonella-specific 5'-nuclease real-time PCR with
      an exogenous internal amplification control. Because a two-step enrichment was
      used, the detection limit for dead S. enterica cells in artificially contaminated
      ice cream and salami samples was high at 10(7 )CFU (25 g)(-1), eliminating
      potential false-positive results. When the method was evaluated with a range of
      100 naturally contaminated food samples, three positive samples were detected by
      both the real-time PCR-based method and by the standard microbiological method,
      according to EN ISO 6579. When the real-time PCR-based method was evaluated
      alongside the standard microbiological method according to EN ISO 6579 with 36
      food samples artificially contaminated at a level of 10(0 )CFU (25 g)(-1),
      identical results were obtained from both methods. CONCLUSIONS: The real-time PCR
      based method involving a two-step enrichment produced equivalent results to EN
      ISO 6579 on the day after sample receipt. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The developed method is suitable for rapid detection of S. enterica in food.

PMID- 18346137
TI  - Evaluation of recA sequencing for the classification of Aeromonas strains at the
      genotype level.
AB  - AIMS: To evaluate the usefulness of partial recA sequences for the identification
      of Aeromonas strains at the genotype level. METHODS AND RESULTS: A partial recA
      sequence was obtained from 21 type or reference strains and 33 Aeromonas
      isolates, collected in the South of Switzerland from human, animal and aquatic
      environments. The 272 bp long recA fragments showed a mean interspecies
      divergence of 7.8% and allowed the classification of strains at genotype level.
      However, some discrepancies could be observed with other gene sequence based
      analyses in the classification of some strains. CONCLUSIONS: The 272 bp long recA
      fragment is a good molecular marker to infer taxonomy of members of the genus
      Aeromonas, even if the primers we chose for the amplification did not allow its
      direct sequencing. SIGNIFICANCE AND IMPACT OF THE STUDY: In the genus Aeromonas,
      nucleotide sequences of some protein-encoding genes have already been evaluated
      as molecular markers to be used in taxonomical and epidemiological researches.
      This study suggests the usefulness of a recA fragment as a further sequence to
      investigate for these purposes.

PMID- 18346138
TI  - Genotypic analysis of Candida albicans isolates obtained from removable
      prosthesis wearers.
AB  - AIMS: To assess of the genotypic diversity of Candida albicans isolated from
      removable prosthesis wearers, with and without denture-related stomatitis (DRS).
      The occurrence of different genotypes in pathological and control cases was
      investigated. METHODS AND RESULTS: One hundred and sixty-four isolates of C.
      albicans obtained from different oral cavity locations were compared by randomly
      amplified polymorphic DNA (RAPD). The coherence of this analysis was confirmed by
      genotyping a selected group of isolates with pulsed field gel electrophoresis
      (PFGE). Among the 164 isolates, 150 were grouped into seven groups on the basis
      of their RAPD patterns. Three of these groups (comprising 54 isolates) had
      significant (alpha < 0.10) predominance of clinical or control cases. For the
      other isolates, no significant differences were observed between control and DRS
      cases. Occasionally, more than one genotype was found in the same person. These
      findings were sustained by PFGE analysis. No relevant associations between the
      genotypic patterns and pathology level were found. CONCLUSIONS: This study
      evidenced that C. albicans with similar genotypes may be found in individuals
      with DRS and in control cases. SIGNIFICANCE AND IMPACT OF THE STUDY: This
      conclusion hints the involvement of other aetiological factors that alone or in
      association with C. albicans may trigger the emergence of DRS.

PMID- 18346139
TI  - Thromboelastographic tracings in retired racing greyhounds and in non-greyhound
      dogs.
AB  - BACKGROUND: Bleeding disorders in patients with normal coagulation test results
      are frequently reported in Greyhounds. The purpose of this study was to compare
      Greyhounds to non-Greyhounds by thromboelastography (TEG). HYPOTHESIS: TEG
      parameters in Greyhounds are different from those in non-Greyhounds. ANIMALS:
      Forty-three healthy dogs (28 Greyhounds and 15 non-Greyhounds) based on the
      results of physical examination, CBC, activated partial thromboplastin time,
      prothrombin time, fibrinogen, and platelet count. MATERIALS AND METHODS:
      Recalcified citrated native TEGs were performed in both groups; data were
      compared using Student's, Mann-Whitney, and Pearson's statistical tests. RESULTS:
      In Greyhounds, mean +/- SD were as follows: R-time 4.3 +/- 1.7 minutes, K-time
      3.8 +/- 1.4 minutes, angle (alpha) 50.0 +/- 8.0 degrees , maximum amplitude (MA)
      47.6 +/- 5.6 mm, clot strength (G) 4,647 +/- 1,097 dyn/cm2, and percent lysis at
      60 minutes (LY60) 2.8 +/- 5.0%. In the non-Greyhounds they were R-time 3.7 +/-
      1.6 minutes, K-time 2.5 +/- 0.9 minutes, angle 59.8 +/- 7.0 degrees , MA 53.1 +/-
      5.6 mm, G 5,811 +/- 1,256 dyn/cm2, and LY60 3.1 +/- 2.5%. All parameters were
      significantly different between the groups, except for R-time and LY60.
      CONCLUSION: In Greyhounds, clotting kinetics are slower and clot strength are
      weaker than in non-Greyhounds, supporting the increased tendency to bleed
      observed after minor trauma or surgical procedures in the breed. The findings may
      also be attributed to blood viscosity or to the concentration of citrate in the
      sample (ie, Greyhounds have higher hematocrit and less plasma per unit volume).

PMID- 18346140
TI  - Idiopathic immune-mediated hemolytic anemia: treatment outcome and prognostic
      factors in 149 dogs.
AB  - BACKGROUND: Canine idiopathic immune-mediated hemolytic anemia (IMHA) is
      associated with a high mortality, especially in the 1st 2 weeks after diagnosis
      despite treatment. OBJECTIVES: To determine treatment outcome and identify
      prognostic variables in order to define areas of future research. ANIMALS: One
      hundred forty-nine dogs with hematocrit <30% and either a positive Coombs' test
      or spherocytosis and with no evidence of disease that can trigger IMHA were
      included. METHODS: Retrospective cohort study. All dogs were treated with
      prednisolone and azathioprine according to a standard protocol. Survival analysis
      was performed by the Kaplan-Meier method. Variables recorded at the time of
      diagnosis were tested as possible prognostic variables in a univariate and
      multivariate Cox proportional hazard model. RESULTS: The main predictors for
      mortality in dogs with idiopathic IMHA are the presence of increased plasma urea
      concentration, bands, thrombocytopenia, and petechiae at the time of diagnosis.
      The estimated Kaplan-Meier half-year survival was 72.6% (95% confidence interval
      [CI]: 64.9-81.3%). Mortality occurred mostly within the 1st 2 weeks. Cox
      proportional hazards analysis indicated that increased plasma urea concentration,
      icterus, and petechiae were the major independent predictors of mortality in the
      1st 2 weeks. In most dogs that survived IMHA, a 3-month protocol of azathioprine
      with prednisolone maintained clinical remission. The estimated half-year survival
      for dogs that survived the 1st 2 weeks was 92.5% (95% CI: 86-99.3%). CONCLUSIONS
      AND CLINICAL IMPORTANCE: If the dogs survived IMHA, a 3-month protocol of
      prednisolone and azathioprine was effective with regard to survival and clinical
      outcome. Future research should be directed at identifying whether thrombotic
      tendency in dogs with IMHA is the main contributor to the development of
      increased plasma urea concentration, icterus, thrombocytopenia, and petechiae.

PMID- 18346141
TI  - Thromboelastographic evaluation of hemostatic function in dogs with disseminated
      intravascular coagulation.
AB  - BACKGROUND: There is considerable variation in the coagulation profile of dogs
      with disseminated intravascular coagulation (DIC), making it difficult to assess
      overall hemostatic function. OBJECTIVES: To characterize the overall hemostatic
      state in dogs with DIC, by use of tissue factor-activated thromboelastography (TF
      TEG), and to determine whether there is an association between hemostasis and
      outcome. ANIMALS: 50 dogs with DIC. METHODS: Dogs admitted to the intensive care
      units, with an underlying disease known to predispose to DIC, were prospectively
      assessed with TF-TEG. Citrated blood samples were collected daily during
      hospitalization and an extended coagulation panel and TF-TEG were performed.
      Diagnosis of DIC was based on expert opinion. RESULTS: Hemostatic dysfunction was
      observed on the TF-TEG profile in 33/50 of the dogs, of which 22/50 were
      hypercoagulable and 11/50 were hypocoagulable based on the TF-TEG G value alone.
      There were significant differences in k, alpha, and MA values (P < .0001) among
      hypo-, normo-, and hypercoagulable dogs. There was a significant difference in
      case fatality rate between hypo- (64%) and hypercoagulable (32%) dogs (relative
      risk = 2.38; P= .04). Dogs that died had significantly lower antithrombin
      activity (P= .03) and higher d-dimer concentration (P= .03) than survivors.
      CONCLUSIONS: The most common overall hemostatic abnormality in dogs diagnosed
      with DIC was hypercoagulability, and there was significant difference in survival
      between hyper- and hypocoagulable dogs. The results suggest TF-TEG is valuable in
      the assessment of hemostatic function in dogs diagnosed with DIC.

PMID- 18346142
TI  - The effect of adding oral dexamethasone to feed alterations on the airway cell
      inflammatory gene expression in stabled horses affected with recurrent airway
      obstruction.
AB  - BACKGROUND: Chemokine expression in airway epithelium and bronchoalveolar lavage
      fluid (BALF) cells of horses with recurrent airway obstruction (RAO) is
      increased. HYPOTHESIS: For RAO-affected horses that are stabled and fed a
      pelleted ration, the addition of oral dexamethasone further improves pulmonary
      function and reduces inflammatory gene expression in pulmonary cells. ANIMALS:
      Twelve RAO-affected horses. METHODS: In a randomized cross-over experiment, the
      effect of feeding pellets in lieu of hay to stabled, RAO-affected horses was
      compared with the effect of feeding pellets and administering a 21-day decreasing
      dose regimen of oral dexamethasone on the expression (by kinetic polymerase chain
      reaction) of interleukin-8 (IL-8), chemokine (C-X-C motif) ligand 2 (CXCL2), IL
      1beta, IL-6, and beta-actin in the BALF cells and of IL-8, CXCL2, 2 IL-1 receptor
      (IL-1R2), Toll-like receptor 4 (TLR4), and glyceraldehyde 3-phosphate
      dehydrogenase in the bronchial epithelium 2 days after the final dose. RESULTS:
      Both treatments reduced airway neutrophilia and breathing efforts but the
      addition of dexamethasone was associated with fewer treatment failures. Compared
      with feed changes alone, dexamethasone administration further reduced the
      expression of IL-8, CXCL2, and IL-1beta in the BALF cells 3.3-, 2.5-, and 4.7
      fold, respectively. In the airway epithelium, both treatments were equally
      efficacious in reducing the expression of IL-8 and CXCL2 expression relative to
      pretreatment values, but either treatment failed to alter the expression of IL
      1R2 and TLR4. CONCLUSIONS AND CLINICAL IMPORTANCE: For a rapid and consistent
      improvement in pulmonary function and a reduction in inflammatory gene expression
      of the BALF cells, a decreasing dose of oral dexamethasone in combination with
      feed alterations is more efficacious for horses that must remain stabled.

PMID- 18346143
TI  - Parenteral selenium and vitamin E supplementation of weaned beef calves.
AB  - BACKGROUND: The weaning process in beef calves elicits physiological stress
      responses that can negatively affect performance and health. Supplementation of
      vitamins and minerals, particularly selenium (Se) and vitamin E, might be
      warranted. HYPOTHESIS: That parenteral administration of Se or vitamin E would
      correct or prevent deficiencies of these nutrients in postweaned beef calves
      during a backgrounding period (42 days after weaning). ANIMALS: One hundred and
      forty-four weaned steers (200-250 kg) in 3 trials. METHODS: One trial was
      conducted with cattle on a dry lot fed a total mixed ration and 2 trials were
      conducted on cattle on pasture. Selenium was administered at 0.05 mg/kg BW (SC)
      and vitamin E was administered at 1500 IU on days 0 and 28 (SC). RESULTS: A
      treatment effect attributable to Se or vitamin E supplementation on average daily
      gain was not detected in any trials. Parenteral supplementation with Se on days 0
      and 28 resulted in higher serum Se concentrations as compared with controls on
      day 42. Parenteral supplementation with Se on days 0 and 28 improved Se status
      from marginal to adequate in 1 trial. Parenteral supplementation with vitamin E
      did not improve serum vitamin E concentrations in any experiment. CONCLUSIONS AND
      CLINICAL IMPORTANCE: Supplementation with vitamin E or Se or a combination of
      both did not have a significant effect on calf performance during the 42-day
      backgrounding period.

PMID- 18346144
TI  - Heart murmurs and valvular regurgitation in thoroughbred racehorses: epidemiology
      and associations with athletic performance.
AB  - BACKGROUND: Cardiac murmurs associated with valvular regurgitation occur commonly
      in conditioned performance horses, but their association with athletic
      performance is unknown. HYPOTHESIS: Cardiac valvular regurgitation has a negative
      association with race performance. ANIMALS: Five hundred and twenty-six "race
      fit" Thoroughbred racehorses engaged in either flat (race distance 1,000-2,500 m)
      or jump racing (race distance 3,200-6,400 m). METHODS: Cardiac auscultation and
      color flow Doppler (CFD) echocardiography were performed on 777 occasions. The
      associations between the presence and severity of either an audible cardiac
      murmur or valvular regurgitation assessed by CFD, and published, objective
      measures of race performance were determined using a standard regression
      approach. RESULTS: The prevalence of murmurs and of regurgitation varied
      significantly between racetypes (P<.02), generally increasing from 2-year olds to
      chasers. There were no consistent associations between racing performance and
      either grade of murmur or regurgitation, whether the presence or absence of
      regurgitation or murmur, or only murmurs > or =3/6 or regurgitation > or =6/9,
      were considered. CONCLUSIONS AND CLINICAL IMPORTANCE: There were differences in
      prevalence and severity of murmurs of atrioventricular and aortic valve
      regurgitation between racehorses in different disciplines. Data also showed that
      neither regurgitation nor murmurs were negatively associated with Timeform
      rating, an index of UK racehorse quality, in any of the groups of racehorses
      studied.

PMID- 18346145
TI  - Effect of spironolactone on diastolic function and left ventricular mass in Maine
      Coon cats with familial hypertrophic cardiomyopathy.
AB  - BACKGROUND: Myocardial fibrosis occurs in cats with hypertrophic cardiomyopathy
      (HCM), and is one factor that leads to diastolic dysfunction. Spironolactone
      (SPIR) reduces myocardial fibrosis in several models of HCM and in humans with
      cardiac disease. HYPOTHESIS: SPIR will improve diastolic function and reduce left
      ventricular (LV) mass in Maine Coon cats with HCM. METHODS: Maine Coon cats with
      familial HCM were included if there was concentric hypertrophy (> or =6 mm end
      diastolic wall thickness) and decreased early lateral mitral annular velocity
      (Em) or summated early and late mitral annular velocity (EAsum) measured by
      pulsed wave tissue Doppler imaging echocardiography. Cats were paired by Em-EAsum
      and randomized to receive 2 mg/kg SPIR (n = 13) or placebo (n = 13) PO q12 h for
      4 months. Em-EAsum, systolic velocity, LV mass, and the ratio of left atrial to
      aortic diameter were measured at baseline, 2 months, and 4 months. Statistical
      analysis included 2-way repeated measures analysis of variance and the Student's
      t-test. RESULTS: Plasma aldosterone concentration increased in cats treated with
      SPIR (235 ng/mL, baseline; 935 ng/mL, 2 months; 1,077 ng/mL, 4 months; P < .001
      at 2 and 4 months). No significant treatment effect was identified for early or
      early-late summated diastolic mitral annular velocity or any other variable
      except plasma aldosterone concentration. Severe facial ulcerative dermatitis
      developed in 4 of 13 cats treated with SPIR, requiring discontinuation of the
      drug. CONCLUSION: SPIR did not improve Em or EAsum of the lateral mitral annulus
      or alter LV mass over 4 months. One third of cats treated with SPIR developed
      severe ulcerative facial dermatitis.

PMID- 18346146
TI  - The bone biologic effects of zoledronate in healthy dogs and dogs with malignant
      osteolysis.
AB  - BACKGROUND: Malignant osteolysis is a process whereby cancer cells in concert
      with osteoclasts erode bone matrix. Aminobisphosphonates (NBPs) such as
      zoledronate induce osteoclast apoptosis and thereby decrease malignant skeletal
      destruction, severity of bone pain, and frequency of pathologic fracture.
      HYPOTHESIS: IV-administered zoledronate will reduce homeostatic bone turnover in
      healthy dogs and pathologic bone resorption in dogs diagnosed with primary and
      secondary bone tumors. ANIMALS: Six healthy dogs and 20 dogs with naturally
      occurring primary or metastatic bone tumors were administered zoledronate IV.
      METHODS: Prospective study: In all dogs, healthy (n = 6) and with malignant
      osteolysis (n = 20), the bone biologic effects of zoledronate were evaluated by
      quantifying changes in serum C-telopeptide (CTx) or urine N-telopeptide (NTx)
      concentrations or both. In dogs with osteosarcoma (OSA) (n = 10), serial changes
      in tumor relative bone mineral density (rBMD) assessed by dual-energy x-ray
      absorptiometry were used to characterize zoledronate's antiresorptive effects
      within the immediate tumor microenvironment. Additionally, the biochemical
      tolerability of zoledronate was assessed in 9 dogs receiving multiple (> or =2)
      consecutive treatments. RESULTS: All dogs had significant reductions in serum CTx
      or urine NTx concentrations or both after zoledronate administration. In a subset
      of dogs with appendicular OSA, reduced urine NTx concentrations and increased
      primary tumor rBMD coincided with improved limb usage as reported by pet owners
      in dogs treated with zoledronate and concurrent oral analgesics. Multiple
      zoledronate infusions were not associated with biochemical evidence of toxicosis.
      CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with skeletal neoplasms, IV
      administered zoledronate exerts bone biologic effects, appears safe, and can
      provide pain relief.

PMID- 18346147
TI  - Cervical vertebral spinal hematomas in 4 horses.

PMID- 18346148
TI  - Enhanced bactericidal activity against Escherichia coli in calves fed Morinda
      citrifolia (Noni) puree.
AB  - BACKGROUND: Although adequate colostrum intake and properly used antibiotics can
      provide much protection for the bovine neonate, increased antibiotic scrutiny and
      consumer demand for organic products have prompted investigations of natural
      immunomodulators for enhancing calf health. One plant-based immunomodulator,
      Morinda citrifolia (noni) fruit, is a well-recognized natural product that has a
      broad range of immunomodulatory effects. HYPOTHESIS: Neonatal calves fed noni
      puree would demonstrate whole blood phagocytic capacity in Gram-negative and Gram
      positive in vitro assays. ANIMALS: Blood samples from 18 neonatal Holstein bull
      calves. METHODS: Calves were divided into 2 groups: Group 1 comprised control
      calves, whereas Group 2 received 30 mL of noni puree twice a day in milk
      replacer. Day 0 blood samples were obtained between 36 and 48 hours of age before
      the first feeding of puree. Ethylenediaminetetraacetic acid anticoagulated blood
      was collected from each calf on days 0, 3, 7, and 14. Bactericidal assays were
      performed to estimate the percentage killing of Escherichia coli and
      Staphylococcus epidermidis. RESULTS: Blood samples from noni puree-fed calves
      displayed significantly more E. coli bacterial killing than did controls on day
      14, and although differences were not significant on days 0, 3, and 7, bacterial
      killing progressively increased over time. There was no significant difference
      between the groups for S. epidermidis killing. CONCLUSIONS AND CLINICAL
      IMPORTANCE: The immunomodulatory effect of noni puree may prove valuable in the
      future as production animal antibiotic use becomes more restricted. Additional
      clinical trials are warranted to investigate the clinical application of noni
      puree in promoting calf health.

PMID- 18346149
TI  - Detection of Bartonella henselae in the blood of 2 adult horses.
AB  - BACKGROUND: Bartonella spp. are emerging zoonotic agents that have been found in
      a wide variety of domestic animals and wildlife and cause a number of clinical
      syndromes. Bartonella sp. infection has been identified in a growing number of
      animal species, including cats, rodents, porpoises, and canids, but has not been
      reported in horses. OBJECTIVE: To document the presence of Bartonella sp. in the
      blood of horses. ANIMALS: One horse with chronic arthropathy and 1 horse with
      presumptive vasculitis. METHODS: Blood samples were tested for the presence of
      Bartonella sp. by a combination of multiplex real-time polymerase chain reaction
      and enrichment culture technique. RESULTS: Bartonella henselae was isolated or
      detected in the blood of both horses. CONCLUSION AND CLINICAL IMPORTANCE:
      Bartonella henselae infection should be investigated as the cause of disease in
      horses.

PMID- 18346150
TI  - Canine lymphoproliferative disease characterized by lymphocytosis:
      immunophenotypic markers of prognosis.
AB  - BACKGROUND: Canine lymphoproliferative disease often presents with lymphocytosis
      and is immunophenotypically diverse. HYPOTHESIS: Immunophenotype predicts
      prognosis in canine lymphoproliferative disorders involving circulating
      lymphocytosis. ANIMALS: Dogs that had peripheral blood evaluation performed by
      flow cytometry by the Clinical Immunology Service at Colorado State University
      between 2003 and 2005. METHODS: Outcome data regarding treatment and survival
      were sought on patients with lymphocytosis comprising a single lymphocyte subset.
      Ninety-six patients that met the inclusion criteria had sufficient follow-up
      information to be included in the study. RESULTS: Four main phenotypic
      classifications were found: CD8+ T-cell, CD21+ B-cell, CD4-8-5+ (aberrant T-cell
      phenotype), and CD34+ (undifferentiated progenitor). Expression of CD34 predicted
      poor outcome with median survival of 16 days (P < .0001) compared with other
      phenotypes. Within the CD8+ phenotype, dogs presenting with a lymphocytosis
      >30,000 lymphocytes/muL had significantly shorter median survival (131 days) than
      those presenting with <30,000 lymphocytes/muL (1098 days, P < .0008). Within the
      T-cell leukemias, there was no difference in outcome between dogs with CD4-8-5+
      leukemia and dogs with the CD8+ T-cell phenotype nor was the loss of expression
      of the pan-leukocyte marker CD45 associated with decreased survival time. A CD21+
      lymphocytosis composed of large cells was associated with shorter survival time
      (129 days) than those with smaller circulating cells (median survival not
      reached, P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Immunophenotyping
      provides an objective method for determining prognosis in lymphoproliferative
      disorders characterized by lymphocytosis.

PMID- 18346151
TI  - Renal toxicity mediated by glucose degradation products in a rat model of
      advanced renal failure.
AB  - BACKGROUND: In peritoneal dialysis (PD) residual renal function contributes to
      improved patient survival and quality of life. Glucose degradation products (GDP)
      generated by heat sterilization of PD fluids do not only impair the peritoneal
      membrane, but also appear in the systemic circulation with the potential for
      organ toxicity. Here we show that in a rat model of advanced renal failure, GDP
      affect the structure and function of the remnant kidney. MATERIALS AND METHODS:
      Sprague-Dawley rats were randomly assigned to a two stage subtotal nephrectomy
      (SNX) or sham operation and were left untreated for 3 weeks. The SNX + GDP group
      continuously received chemically defined GDP intravenously for 4 weeks; the SNX
      and the sham-operated rats remained without GDP. The complete follow-up for all
      groups was 7 weeks postoperatively. We analysed renal damage using urinary
      albumin excretion as well as a semiquantitative score for glomerulosclerosis and
      tubulointerstitial damage, as well as for immunohistochemical analyses. RESULTS:
      The SNX + GDP rats developed significantly more albuminuria and showed a
      significantly higher score of glomerulosclerosis index (GSI) and
      tubulointerstitial damage index (TII) as compared to SNX or control rats. In the
      SNX + GDP group the expression of carboxymethyllysine and methylglyoxal was
      significantly higher in the tubulointerstitium and the glomeruli compared to the
      SNX rats. Caspase 3 staining and TUNEL assay were more pronounced in the
      tubulointerstitium and the glomeruli of the SNX + GDP group. In SNX + GDP
      animals, the expression of the slit diaphragm protein nephrin, was significantly
      lower compared to SNX or control animals. CONCLUSION: In summary, our data
      suggests that GDP can significantly advance chronic kidney disease and argues
      that PD solutions containing high GDP might deteriorate residual renal function
      in PD.

PMID- 18346152
TI  - Mechanisms of regulatory T-cell suppression - a diverse arsenal for a moving
      target.
AB  - Naturally-occurring regulatory T cells (Tregs) are emerging as key regulators of
      immune responses to self-tissues and infectious agents. Insight has been gained
      into the cell types and the cellular events that are regulated by Tregs. Indeed,
      Tregs have been implicated in the control of initial activation events,
      proliferation, differentiation and effector function. However, the mechanisms by
      which Tregs disable their cellular targets are not well understood. Here we
      review recent advances in the identification of distinct mechanisms of Treg
      action and of signals that enable cellular targets to escape regulation. Roles
      for inhibitory cytokines, cytotoxic molecules, modulators of cAMP and cytokine
      competition have all been demonstrated. The growing number of inhibitory
      mechanisms ascribed to Tregs suggests that Tregs take a multi-pronged approach to
      immune regulation. It is likely that the relative importance of each inhibitory
      mechanism is context dependent and modulated by the inflammatory milieu and the
      magnitude of the immune response. In addition, the target cell may be
      differentially susceptible or resistant to distinct Treg mechanisms depending on
      their activation or functional status at the time of the Treg encounter.
      Understanding when and where each suppressive tool is most effective will help to
      fine tune therapeutic strategies to promote or constrain specific arms of Treg
      suppression.

PMID- 18346154
TI  - Prevalence of the diabetic foot syndrome at the primary care level in Germany: a
      cross-sectional study.
AB  - AIMS: The diabetic foot syndrome (DFS) is an important complication of diabetes
      mellitus resulting in amputations, disability and reduced quality of life. DFS is
      preventable. The aim was to investigate the prevalence of the DFS at the primary
      care level in Germany. METHODS: This was a cross-sectional study of the
      prevalence of DFS, associated factors and glycaemic control at the primary care
      level in Germany. We examined an unselected sample of participants with known
      diabetes who were insured by Deutsche BKK, a large healthcare insurer. RESULTS:
      Three hundred and forty-one general practitioners examined 4778 participants with
      diabetes mellitus: 366 (7.7%) participants (mean age 49 +/- 16 years) had Type 1
      and 4412 participants (mean age 66 +/- 10 years) had Type 2 diabetes. DFS was
      diagnosed in 138 patients, resulting in a prevalence of 3.6%[95% confidence
      interval (CI) 1.9, 6.0] in Type 1 and 2.8% (95% CI 2.3, 3.4) in Type 2 diabetes.
      DFS was independently associated with age, duration of diabetes, height, current
      smoking and insulin therapy. There was no significant effect of glycaemic control
      on the risk of DFS. The prevalence of other abnormal foot findings was:
      peripheral neuropathy 9.7%, peripheral arterial disease 14.8% (absent dorsalis
      pedis), 12.4% (absent tibialis posterior), acute diabetic foot ulcer 0.8%,
      amputations of lower extremities 1.5%, and amputations limited to toes 0.5%.
      CONCLUSIONS: The prevalence of the DFS at the primary care level in Germany is
      2.9%. Almost 50% of patients with DFS had major or minor amputations. Common risk
      factors such as hyperkeratosis and poor glycaemic control can be modified.
      Effective therapeutic approaches in addition to methods for primary and secondary
      prevention of DFS should be used more widely.

PMID- 18346153
TI  - Apoptosis-induced inhibition of CD1d-mediated antigen presentation: different
      roles for caspases and signal transduction pathways.
AB  - The stimulation of programmed cell death can either enhance or inhibit antigen
      presentation by classic major histocompatibility complex molecules. In the
      current study, we report that the induction of apoptosis by topoisomerase I
      inhibition or elevation of intracellular ceramide levels substantially impairs
      CD1d-mediated antigen presentation. In the former case, such a reduction occurred
      via the regulation of both the p38 mitogen-activated protein kinases and protein
      kinase C delta signal transduction pathways as well as the caspase cascade,
      whereas the latter was p38-(but not caspase)-dependent. Confocal microscopic
      analysis showed an altered intracellular distribution of CD1d following the
      inhibition topoisomerase I or by an increase in intracellular ceramide levels,
      that was prevented by p38 and caspase inhibitors. Thus, the induction of
      apoptosis in antigen presenting cells severely compromises CD1d-mediated antigen
      presentation by multiple mechanisms.

PMID- 18346155
TI  - Six-year incidence of lower extremity arterial disease and associated risk
      factors in Type 1 diabetic African-Americans.
AB  - AIMS: To report the 6-year incidence of, and risk factors for, lower extremity
      arterial disease (LEAD) in African-Americans with Type 1 diabetes mellitus.
      METHODS: African-Americans (n = 483) with Type 1 diabetes were re-examined 6
      years after an original visit. At both visits, patients underwent a structured
      clinical interview which included history of amputation or leg angioplasty
      because of poor circulation in lower extremities; ocular examination; masked
      grading of seven stereoscopic fundus photographs; and blood pressure
      measurements. Biological tests included blood and urine assays. RESULTS: Of the
      483 patients who had a 6-year follow-up, 457 had no LEAD at the baseline
      examination. Of these 457 patients, 26 (5.7%) developed LEAD over the 6-year
      follow-up. Six-year incidence of LEAD was significantly associated with baseline
      older age (P = 0.0002) and longer duration of diabetes (P < 0.0001). Multiple
      logistic regression analysis showed that baseline longer duration of diabetes,
      male gender, higher systolic blood pressure, retinopathy severity, and presence
      of foot ulcers were significant and independent risk factors for incidence of
      LEAD. CONCLUSIONS: Blood pressure control and prevention and treatment of foot
      ulcers may be helpful in reducing the morbidity associated with LEAD in African
      Americans with Type 1 diabetes.

PMID- 18346156
TI  - Vibrotactile sense in median and ulnar nerve innervated fingers of men with Type
      2 diabetes, normal or impaired glucose tolerance.
AB  - AIMS: To investigate vibrotactile sense (large fibre neuropathy) at different
      frequencies in index and little fingers (median and ulnar nerves, respectively)
      of subjects with diabetes, or impaired (IGT) or normal glucose tolerance (NGT).
      METHODS: Vibration thresholds (tactilometry at seven frequencies (8, 16, 32, 64,
      125, 250 and 500 Hz)) and median nerve function (electrophysiology) were examined
      in men (age 73.4 +/- 0.12 years; n = 58, mean +/- sd) with persistent NGT (n =
      28) or IGT (n = 7) or with Type 2 diabetes mellitus (T2DM) (n = 23) for > 15
      years. RESULTS: HbA1c was increased and vibrotactile sense (sensibility index)
      was impaired in index and little fingers in men with T2DM. Vibration thresholds
      were particularly increased at 16, 250 and 500 Hz in the little finger (ulnar
      nerve). T2DM subjects showed electrophysiological (gold standard) signs of
      neuropathy in the median nerve. Although subjects with persistent IGT had higher
      HbA1c, vibrotactile sensation and electrophysiology remained normal. HbA1c did
      not correlate with vibrotactile sense or electrophysiology, but the latter two
      correlated with respect to Z-score (sign of neuropathy) in forearm (NGT) and at
      wrist level (NGT and DM). CONCLUSIONS: Vibration thresholds are increased in the
      finger pulps in T2DM subjects, particularly at specific frequencies in ulnar
      nerve innervated finger pulps. Neuropathy is not present in IGT. Tactilometry,
      with a multi-frequency approach, is a sensitive technique to screen for large
      fibre neuropathy in T2DM. Frequency-related changes may mirror dysfunction of
      various receptors.

PMID- 18346157
TI  - Health utility values associated with diabetic retinopathy.
AB  - AIMS: Different estimates exist regarding the impact of diabetic retinopathy (DR)
      on health utility. A previously reported prospective observational study has
      reported much larger decrements in self-reported utility than generic utility
      data from the UK Prospective Diabetes Study and the Lipids in Diabetes Study. The
      present study was designed to estimate utility loss using multiple methods.
      METHODS: Detailed health state descriptions reflecting declining DR (five
      different visual acuity levels), neuropathy and nephropathy were validated with
      patients and used to elicit utility values from people with DR, people with
      diabetes and members of the UK general public using standard gamble. In addition,
      a larger sample of people with retinopathy completed different health-related
      quality of life measures in an interview [EuroQoL (EQ-5D), Health State Utilities
      Index (HUI)-3, and National Eye Institute Visual Functioning Questionnaire-25].
      RESULTS: The utility scores from the standard gamble interviews were not
      significantly different between the three groups. There was a decline in utility
      from 6/6 vision to counting fingers of -0.244. The utility data derived from the
      generic measures revealed an equivalent decline of -0.41 on both the EQ-5D single
      index and the HUI-3. CONCLUSIONS: This study has re-examined the utility
      decrements associated with DR and has identified much larger declines in utility
      than previously reported. The study has also reported the utility values of
      patients with retinopathy as assessed by standard gamble. We believe that this
      may be the first study to report utility values for health states associated with
      vision loss which have been elicited from patients with vision loss.

PMID- 18346158
TI  - Lower attendance rates and higher fasting glucose levels in the month of Ramadan
      in patients with diabetes in a Muslim country.

PMID- 18346159
TI  - Risk factors for diabetic retinopathy in a South Indian Type 2 diabetic
      population--the Chennai Urban Rural Epidemiology Study (CURES) Eye Study 4.
AB  - AIMS: To determine risk factors for diabetic retinopathy (DR) in an urban South
      Indian Type 2 diabetic population. METHODS: The Chennai Urban Rural Epidemiology
      Study is a large cross-sectional study conducted in Chennai, South India. A total
      of 1736 Type 2 diabetic subjects were recruited for this study, which included
      1382 known diabetic subjects (90.4% response rate) and 354 randomly selected,
      newly detected diabetic subjects diagnosed by oral glucose tolerance test. All
      subjects underwent four-field stereo retinal colour photography, graded by the
      Early Treatment Diabetic Retinopathy Study protocol. RESULTS: Of the 1736 Type 2
      diabetic subjects photographed, photographs could be graded in 1715 subjects.
      Stepwise ordinal logistic regression analysis revealed that male gender (P =
      0.041), duration of diabetes (P < 0.0001), glycated haemoglobin (HbA(1c); P <
      0.0001), macroalbuminuria (P = 0.0002) and insulin therapy (P = 0.0001) were
      significantly associated with severity of DR. The risk for developing DR was 7.7
      times (95% confidence interval 4.71-12.48, P < 0.0001) for elevated postprandial
      plasma glucose levels compared with 4.2 times (95% confidence interval 2.78-6.34,
      P < 0.0001) for elevated fasting plasma glucose when the fourth quartile values
      were compared with the first quartile glucose values. CONCLUSIONS: In South
      Indian Type 2 diabetic subjects, duration of diabetes, HbA1c, male gender,
      macroalbuminuria and insulin therapy were independent risk factors for severity
      of DR. Postprandial hyperglycaemia indicated a higher risk for DR compared with
      elevated fasting plasma glucose levels.

PMID- 18346160
TI  - Varenicline may trigger severe hypoglycaemia in Type 1 diabetes.
AB  - BACKGROUND: Varenicline is a new drug indicated for smoking cessation. It has
      primarily been investigated in healthy adults. The commonest side-effects are
      nausea, headache, sleep disturbance, constipation, flatulence and vomiting.
      Hypoglycaemia has not been reported. As smoking cessation is important to reduce
      risk of cardiovascular morbidity, especially in diabetes, use of effective drugs
      indicated for smoking cessation is rational. CASE REPORT: We report multiple
      episodes of severe hypoglycaemia after starting varenicline in a 53-year-old
      woman with Type 1 diabetes. Since onset of diabetes at age 25 years and until
      start of varenicline therapy, she had only experienced one episode of severe
      hypoglycaemia and hypoglycaemia awareness was not impaired. The severe
      hypoglycaemic episodes disappeared after withdrawal of varenicline. CONCLUSIONS:
      We recommend cautious prescription of varenicline, intensified blood glucose
      monitoring and careful education of patients with diabetes treated with
      varenicline. Further investigation of the use of varenicline in patients with
      diabetes is warranted.

PMID- 18346161
TI  - Relationship between gamma-glutamyltransferase and metabolic syndrome in a Korean
      population.
AB  - AIMS: To investigate associations between gamma-glutamyltransferase (GGT) and
      components of metabolic syndrome (MS), insulin resistance and inflammatory
      markers in the Korean population. METHODS: The 3508 subjects enrolled in this
      survey participated in the Korean Rural Genomic Cohort (KRGC) study. Written
      consent was obtained from the local ethical committee. Of these participants,
      1437 were men (mean age 56.9 +/- 7.9 years) and 2071 were women (mean age 55.8 +/
      8.1 years). We measured GGT levels and various biochemical markers. To examine
      insulin resistance status, we used the homeostasis assessment method for insulin
      resistance (HOMA-IR). For inflammatory marker, we used C-reactive protein (CRP)
      levels. RESULTS: Serum GGT levels were significantly higher in the MS group
      compared to the healthy patient group [23 (5-1403) vs. 19 (5-1920) IU/l; P =
      0.01]. The prevalence of MS and adjusted relative risk were both significantly
      increased from the lowest to highest GGT quartiles; these results persisted after
      adjustments for multiple confounders. Positive correlations were established
      between GGT and HOMA-IR or CRP. CONCLUSION: These results suggest that GGT levels
      may be a surrogate marker of insulin resistance, inflammation and MS.

PMID- 18346162
TI  - Cocaine decreases plasma insulin concentrations in non-diabetic subjects: a
      randomized double-blind study.

PMID- 18346163
TI  - Establishing pragmatic estimated glomerular filtration rate thresholds to guide
      metformin prescribing: careful assessment of risks and benefits is required.

PMID- 18346164
TI  - Fatty liver is an independent risk factor for the development of Type 2 diabetes
      in Korean adults.
AB  - AIMS: To investigate whether fatty liver per se is an independent risk factor of
      incident type 2 diabetes mellitus (T2DM) in Koreans. METHODS: We examined the
      clinical and laboratory data of 5372 non-diabetic participants (3670 men and 1702
      women; age 46.8 +/- 8.4 years, range 20-79 years) who underwent voluntary medical
      check-ups in 2000 and follow-up examinations in 2005. RESULTS: Two hundred and
      thirty-three participants (4.3%) developed T2DM after 5 years. Univariate
      analysis showed that the development of diabetes was associated with: male sex;
      family history of diabetes; smoking; older age; higher body mass index (BMI),
      systolic and diastolic blood pressure, fasting plasma glucose (FPG), hepatic
      enzymes, total cholesterol and triglycerides; lower HDL cholesterol; and the
      presence of fatty liver on ultrasonography at baseline. In multiple logistic
      regression models, after adjusting for age, sex and alcohol consumption, patients
      with fatty liver were at significantly higher risk of developing T2DM compared to
      those without fatty liver [relative risk (RR) 3.92, 95% confidence interval (CI)
      2.89-5.31]. After further adjustment for smoking, BMI, triglycerides, HDL
      cholesterol, FPG, alanine aminotransferase and ultrasonographer, fatty liver
      remained significantly associated with the development of T2DM (RR 1.51, 95% CI
      1.04-2.20). Patients with moderate to severe fatty liver had higher risk ratios
      than patients with mild fatty liver. Exclusion of frequent drinkers did not
      attenuate the association. CONCLUSIONS: Fatty liver on ultrasonography is
      associated with the development of T2DM, independently of classical risk factors,
      in Korean adults.

PMID- 18346165
TI  - Should liver function tests be included in definitions of metabolic syndrome?
      Evidence from the association between liver function tests, components of
      metabolic syndrome and prevalent cardiovascular disease.
AB  - AIMS: The definition of metabolic syndrome (MS) continues to be debated and does
      not include abnormal liver function tests (LFTs). This study aims to determine:
      (1) the association between the five ATP3 MS diagnostic components and different
      LFTs, and (2) the association between raised LFTs and prevalent cardiovascular
      disease (CVD). METHODS: A total of 1357 patients, without alcoholism or known
      liver disease, from randomly selected households from rural Victoria, Australia,
      attended for biomedical assessment. Receiver operating characteristic (ROC) areas
      under the curve (AUC) were determined for associations between the ATP3
      diagnostic components, and between LFTs and ATP3 diagnostic components. RESULTS:
      The range of ROC AUC for ATP3 diagnostic components was 0.60-0.77. Waist had the
      strongest association and blood pressure the weakest. The strength of association
      between ATP3 diagnostic components and gamma GT (GGT) was similar (0.63-0.72),
      but was less for alanine transaminase and aspartate transaminase. Using the ROC
      derived GGT cut-off (men 27 IU, women 20 IU), those with MS and a high GGT had
      more CVD than those with MS and a low GGT, and those without MS (18% vs. 10% vs.
      7%, respectively; P < 0.001). Among those with MS, after adjusting for
      covariates, the odds ratio of CVD was 2.66 (1.18-5.96) for a high GGT compared to
      a low GGT. CVD was not significantly more prevalent in MS patients with a low GGT
      compared to non-MS patients. CONCLUSIONS: We suggest that including a raised GGT
      in the criteria for MS could increase its predictive nature for CVD. Prospective
      studies are needed to confirm this finding.

PMID- 18346166
TI  - Subendocardial viability ratio estimated by arterial tonometry: a critical
      evaluation in elderly hypertensive patients with increased aortic stiffness.
AB  - 1. Increased aortic stiffness predisposes to myocardial ischaemia by increasing
      the systolic tension-time index and by decreasing aortic pressure throughout
      diastole. The tonometric subendocardial viability ratio (SEVR) is a non-invasive
      estimate of myocardial perfusion relative to cardiac workload. The hypothesis
      that SEVR is impaired in elderly hypertensives with high aortic pulse pressure
      (PP) was tested in the present study. 2. The SEVR was calculated by radial
      applanation tonometry in 203 subjects. In addition, diastolic time (DT), systolic
      time (ST) and mean diastolic and systolic aortic pressures (Pd and Ps,
      respectively) were calculated. First, 60 subjects matched for age and gender were
      analysed (20 controls, 20 hypertensives with pulse pressure (PP) < or = 60 mmHg,
      20 hypertensives with PP > 60 mmHg; mean (+/-SD) age 64 +/- 9 years; 24 women, 36
      men). The remaining 143 subjects, aged 53 +/- 10 years, were analysed
      subsequently. 3. The SEVR was similar in the three elderly groups (1.39 +/- 0.34,
      1.39 +/- 0.28 and 1.35 +/- 0.25, in controls and hypertensive patients with PP <
      or = 60 and > 60 mmHg, respectively). The SEVR was positively related to DT/ST
      (r(2) = 0.89) and to DT (r(2) = 0.73) and was negatively related to heart rate
      (r(2) = 0.56; P < 0.001 each). However, SEVR was not related to ST, PP, mean Pd
      or mean Ps. At a given DT/ST, SEVR tended to be lower in hypertensives with PP >
      60 mmHg than in hypertensives with normal PP. The positive linear relationship
      between SEVR and DT/ST was confirmed in the remaining 143 subjects (r(2) = 0.90),
      with no influence of aortic pressure. 4. The tonometric SEVR was not impaired in
      elderly hypertensive patients with increased aortic stiffness. In resting elderly
      and middle-aged individuals, the tonometric SEVR was mainly related to DT/ST
      ratio, not to aortic pressure.

PMID- 18346167
TI  - Do we need molecular tomography of a cell and how can it be achieved?
AB  - 1. The spatial relationship between intracellular molecules and their local
      concentrations are two critical parameters required for a better understanding of
      protein-protein interactions in the cell. 2. Determination of the local
      concentration of proteins in individual cells using more sophisticated techniques
      and determination of the spatial relationship between a molecular platform and
      its partners is essential for allow us to obtain more convincing and concrete
      scientific conclusions. 3. As a reasonable goal, development of molecular
      tomography of the cell is proposed.

PMID- 18346168
TI  - Limitation of infarct size by erythropoietin is associated with translocation of
      Akt to the mitochondria after reperfusion.
AB  - 1. The aim of the present study was to determine the critical timing of Akt
      activation and its interaction with the mitochondrial permeability transition
      pore (mPTP) in the mechanism of infarct size limitation by erythropoietin (Epo).
      2. In an isolated, buffer-perfused preparation, rabbit hearts were subjected to
      30 min ischaemia/2 h reperfusion. Infusion of Epo (1 unit/mL) before ischaemia
      reduced infarct size from 36.6 +/- 2.6% of the risk area to 15.4 +/- 3.2%,
      whereas a 10-fold higher dose of Epo infused for 65 min commencing 5 min before
      reperfusion failed to afford significant cardioprotection. The protection
      afforded by Epo pretreatment was abolished by coinfusion of 5 micromol/L
      LY294002, a phosphatidylinositol 3-kinase (PI3-K) inhibitor. Infusion of Epo
      induced phosphorylation of Akt, extracellular signal-regulated kinase, glycogen
      synthase kinase 3beta and p70s6 kinase before ischaemia and tended to enhance
      reperfusion-induced phosphorylation of these protein kinases. Erythropoietin
      increased phospho-Akt in the mitochondria and induced complex formation of Akt
      with adenine nucleotide translocase (ANT), a major subunit of mPTP, upon
      reperfusion. 3. In another series of experiments, cardiomyocytes were isolated
      from rat hearts and loaded with Rhod-2 to determine mitochondrial Ca(2+) levels.
      Increases in mitochondrial Ca(2+) levels following exposure to 1 mmol/L ouabain
      for 30 min were similar in untreated and Epo-pretreated cells. However, ouabain
      induced hypercontracture was significantly suppressed from 45.1 +/- 1.6 to 39.2
      +/- 1.9% by Epo. 4. In conclusion, activation of PI3-K-Akt signalling before
      ischaemia is crucial for Epo-induced myocardial protection and this protection
      may be achieved by complex formation of activated Akt with mPTP components upon
      reperfusion, leading to elevation of the threshold for opening of mPTP.

PMID- 18346169
TI  - Mitemcinal (GM-611), an orally active motilin receptor agonist, improves delayed
      gastric emptying in a canine model of diabetic gastroparesis.
AB  - 1. The aim of the present study was to evaluate the effects of mitemcinal (GM
      611), an orally active motilin receptor agonist, on delayed gastric emptying in a
      canine model of diabetic gastroparesis and to compare these effects with those of
      cisapride. 2. Moderate hyperglycaemia was induced by a single intravenous
      injection of a mixture of streptozotocin (30 mg/kg) and alloxan (50 mg/kg). Dogs
      that maintained moderate hyperglycaemia (fasting plasma glucose 200-300 mg/dL)
      without insulin treatment were selected and gastric emptying in these dogs was
      determined by the paracetamol method. 3. One year after the onset of diabetes,
      there was no difference in the gastric emptying of normal and diabetic dogs.
      However, after 5 years, the diabetic dogs showed delayed gastric emptying. The
      motor nerve conduction velocity of the tibial nerve was significantly lower in
      diabetic dogs compared with normal dogs at both time points. 4. Histopathological
      examination at the end of the study showed that there were fewer nerve fibres in
      both dorsal vagal and tibial nerves of diabetic dogs compared with normal dogs.
      The onset of delayed gastric emptying is thought to have occurred gradually, in
      parallel with abnormal autonomic nerve function induced by the long period of
      moderate hyperglycaemia. 5. Oral administration of mitemcinal (0.125, 0.25 or 0.5
      mg/kg) dose-dependently accelerated delayed gastric emptying, significant at 0.5
      mg/kg, in diabetic dogs, whereas cisapride (1, 3 or 10 mg/kg) had no significant
      effect. These results add to the existing evidence that mitemcinal is likely to
      be useful for treating diabetic gastroparesis.

PMID- 18346170
TI  - Defective intracellular Ca2+ homeostasis contributes to myocyte dysfunction
      during ventricular remodelling induced by chronic volume overload in rats.
AB  - 1. Previous studies have demonstrated progressive ventricular hypertrophy,
      dilatation and contractile depression in response to chronic volume overload.
      Whether this decompensation was related to intrinsic myocyte dysfunction was not
      clear. The present study evaluated ventricular myocyte function at critical times
      during the progression of ventricular remodelling induced by volume overload. 2.
      Chronic volume overload was induced with an infrarenal aortocaval fistula in
      rats. Myocyte contraction and intracellular Ca(2+) concentrations ([Ca(2+)](i))
      were evaluated using a fura-2 fluorescence and edge detection system. Protein
      levels of sarcoplasmic reticulum (SR) Ca(2+) transporters were determined by
      western blots. Progressive ventricular dilatation developed following creation of
      the fistula. Although myocyte function in 5 week fistula rats was comparable to
      that of the control group, myocytes from rats 10 weeks post-fistula demonstrated
      significant depression of cell shortening and peak [Ca(2+)](i). Application of
      isoproterenol (0.1 micromol/L) was not able to compensate for the functional
      deficiency in myocytes from 10 week fistula rats. Caffeine (10 mmol/L) induced SR
      Ca(2+) release, as well as protein expression of SR Ca(2+)-ATPase, and ryanodine
      receptors were reduced in myocytes obtained from the same group of 10 week
      fistula rats. 3. These data indicate that the transition to heart failure
      secondary to chronic volume overload is related to depressed myocyte
      contractility secondary to altered intracellular Ca(2+) homeostasis.

PMID- 18346171
TI  - Long-term exposure to extremely low-frequency magnetic fields impairs spatial
      recognition memory in mice.
AB  - 1. In the present study, we investigated the short- and long-term effects of
      extremely low-frequency (ELF) magnetic fields on spatial recognition memory in
      mice by using a two-trial recognition Y-maze that is based on the innate tendency
      of rodents to explore novel environments. 2. Mice were exposed to 25 or 50 Hz
      electromagnetic fields for either 7 (short term) or 25 days (long term) and then
      tested in the Y-maze. 3. The results indicated that neither short- nor long-term
      exposure to magnetic fields affected the locomotor activity of mice in the Y
      maze. However, long-term exposure to 50 Hz fields reduced recognition of the
      novel arm. 4. Our findings suggest that ELF magnetic fields impair spatial
      recognition memory in the Y-maze depending on the field strength and/or duration
      of exposure.

PMID- 18346172
TI  - Continuous infusion of sivelestat sodium hydrate prevents lipopolysaccharide
      induced intestinal paralysis and hypotension in conscious guinea-pigs.
AB  - 1. Sivelestat sodium hydrate (sivelestat), a neutrophil elastase inhibitor, is
      used to treat acute lung injury associated with systemic inflammatory response
      syndrome, but its effects have not been described for endotoxaemia. In the
      present study, we examined the effects of a continuous infusion of sivelestat on
      intestinal mechanical activity and blood pressure using an endotoxaemic model in
      conscious, unrestrained guinea-pigs. 2. Guinea-pigs underwent laparotomy while
      anaesthetized and were implanted with a force transducer sutured onto the taenia
      caecum. With this transducer, changes in tension in the intestinal longitudinal
      muscle were measured continuously via telemetry. Catheters were inserted into the
      carotid artery and jugular vein, were tunnelled subcutaneously and were accessed
      from the back of the neck. These catheters were connected to a cannula swivel and
      were used to monitor arterial pressure as well as to administer drugs i.v. in
      conscious, unrestrained guinea-pigs. Twenty hours after surgery, guinea-pigs
      received a single dose of lipopolysaccharide (LPS; 0.3 mg/kg, i.p.) 10 min after
      the start of a continuous 2 h i.v. infusion of sivelestat (30 mg/kg per h) or
      vehicle (saline). Elastase activity before and after sivelestat or vehicle
      administration was measured spectrometrically using a specific synthetic
      substrate. 3. We confirmed that intestinal longitudinal muscle tension decreased
      2-3 h after LPS administration in the control group, with a concurrent decline in
      blood pressure. In guinea-pigs treated with sivelestat, the LPS-induced decreases
      in muscle tension and blood pressure were significantly reduced. In LPS-treated
      control guinea-pigs, serum elastase activity was elevated and this increase was
      significantly attenuated by administration of sivelestat. 4. The findings from
      the present study suggest that sivelstat can effectively reduce intestinal
      dysfunction and attenuate LPS-induced decreases in blood pressure in
      endotoxaemia.

PMID- 18346173
TI  - Metformin, arterial function, intima-media thickness and nitroxidation in
      metabolic syndrome: the mefisto study.
AB  - 1. Metabolic syndrome (MS) is one of the greatest public health problems in
      Mexico, where more than 75% of adults in urban populations are overweight or
      obese. Metabolic syndrome has several comorbidities, which result in a high
      cardiometabolic risk. 2. Some of the vasopathogenic phenomena in MS are caused by
      nitroxidant stress, secondary to cardiometabolic dysfunction. 3. The action of
      metformin to diminish or control MS remains a matter of debate. 4. In the present
      study, 60 patients with at least three diagnostic criteria for MS were divided
      into two groups. Both groups received similar dietary counselling, but one group
      was given 850 mg metformin daily. 5. The variables assessed were body mass index,
      waist circumference, systolic and diastolic blood pressures (SBP and DBP,
      respectively), total cholesterol (TC), high- and low-density lipoprotein
      cholesterol, triglycerides (TG), fasting glucose, nitroxidant metabolites (free
      carbonyls, malondialdehyde, dityrosines and advanced oxidative protein products
      (AOPP)), nitric oxide (NO), carotid vascular stiffness, carotid intima-media
      thickness (IMT) and C-reactive protein (CRP). 6. After 1 year follow up, both
      groups reported weight loss, as well as decreases in waist circumference, SBP and
      DBP. 7. Patients on metformin exhibited reductions in TC and IMT and there were
      marked changes in nitroxidation: levels of carbonyls, dityrosines and AOPP were
      reduced, whereas those of NO were increased, indicating better endothelial
      function. In addition, in patients given metformin, CRP levels decreased. 8. In
      conclusion, metformin has a considerable beneficial effect on nitroxidation,
      endothelial function and IMT in patients with MS.

PMID- 18346174
TI  - A new electrophysiological tool to investigate the spatial neuronal projections
      within the myenteric ascending reflex of the mouse colon.
AB  - 1. The intestinal peristaltic reflex is regulated by local microcircuits that,
      upon activation, result in an oral contraction and anal relaxation of the
      circular muscle. This contractile response is associated with typical
      electrophysiological changes in membrane potential resulting from excitatory and
      inhibitory myenteric pathways. 2. The aim of the present study was to investigate
      the influence of local electrical stimulation (ES; single pulses, 15 V, 0.3 msec
      duration) on the ascending gastrointestinal electrophysiological potentials of
      the mouse colon using a novel 12-channel stimulation electrode in a newly
      designed model of the ascending myenteric pathways with simultaneous
      intracellular recording. 3. Local myenteric reflex responses in the proximal
      colon were initiated by ES (12 bipolar stimulation electrodes (SE) 0.7 mm apart
      from each other) and excitatory and inhibitory junction potentials (EJP and IJP,
      respectively) were recorded from circular smooth muscle cells with intracellular
      recording techniques. In vivo colonic propulsion was determined by measuring the
      time to expulsion of a 3 mm glass bead inserted 2.5 cm into the distal colon of
      mouse. 4. Under basal conditions, circular smooth muscle cells displayed a stable
      membrane potential (-56.7 +/- 6.9 mV; n = 13). Electrical stimulation elicited a
      tetrodotoxin (3 micromol/L)-sensitive, neuronal-induced EJP (cholinergic;
      atropine (1 micromol/L) sensitive) and a biphasic IJP. Both the EJP and IJP
      showed characteristic responses dependent on the distance between stimulation and
      recording sites. The EJP could be recorded over long distances, resulting in a
      maximal EJP amplitude at a distance of 10 mm distance (represented by stimulation
      electrodes (SE) number 6/7) and a maximal projection distance of 18-20 mm. Both
      components of IJP were maximal during direct stimulation (at SE1; stimulation at
      the recording site) and gradually decreased to SE6/7 (10 mm). At distances
      greater than 10 mm apart, ES did not produce IJP. The ganglionic blocker
      hexamethonium (10-100 micromol/L) concentration dependently abolished all
      inhibitory junction potentials at distances greater than 10 mm and significantly
      reduced the amplitude of EJP for the first 10 mm. Colonic propulsion was
      decreased by hexamethonium (40 mg/kg) and atropine (0.7 mg/kg). 5. Neuronal
      circuits of the ascending myenteric reflex functionally project distances ranging
      up to 18-20 mm. Our newly designed setup allows simultaneous electrophysiological
      investigations of neuronal microcircuitry within the myenteric plexus over short
      and long distances and enables conclusions to be drawn regarding neuroneuronal
      and neuromuscular transmission.

PMID- 18346175
TI  - Cyp2d6*3, *4, *5 and *6 polymorphisms and antipsychotic-induced extrapyramidal
      side-effects in patients receiving antipsychotic therapy.
AB  - 1. The aim of the present study was to examine the relationship between CYP2D6
      polymorphisms and the risk of antipsychotic (AP)-induced extrapyramidal symptoms
      (EPS) in patients receiving AP treatment. The allele status for CYP2D6*3,
      CYP2D6*4, CYP2D6*5 and CYP2D6*6 was determined in 267 patients receiving AP
      therapy. Seventy-nine cases presenting with EPS (Simpson-Angus Scale 3) and 188
      controls without EPS (Simpson-Angus > 3) took part in the study. 2. We found a
      non-significant over-representation of poor metaboliser genotypes among cases,
      but a significant association between the mutant homozygous genotype for CYP2D6*4
      (odds ratio (OR) 4.1, 95% confidence interval (CI) 1.01-16, permutated P value
      0.01) and the heterozygous genotype for CYP2D6*6 (OR 5.4, 95% CI 1.13-18,
      permutated P value 0.003) and the risk of suffering EPS. 3. These results suggest
      that the CYP2D6 genotype may be a contributory factor in the development of EPS
      in patients undergoing AP therapy.

PMID- 18346176
TI  - Role of Ca2+ stores in acetylcholine-induced all-or-none shortening of smooth
      muscle cells from guinea-pig taenia caecum.
AB  - 1. We have reported previously that isolated single smooth muscle cells from
      guinea-pig taenia caecum respond to acetylcholine (ACh) in an all-or-none manner.
      2. To clarify the roles of intracellular Ca(2+) stores in the all-or-none
      response of isolated smooth muscle cells from guinea-pig taenia caecum to ACh, we
      examined the inositol 1,4,5-trisphosphate (IP(3))-induced contractile response in
      Staphylococcus aureus alpha-toxin-permeabilized smooth muscle cells and the
      effect of depletion of intracellular Ca(2+) stores on the all-or-none response to
      ACh in intact smooth muscle cells. 3. alpha-Toxin-permeabilized smooth muscle
      cells responded to 3-30 nmol/L or 0.3-3 nmol/L IP(3) in the presence of 0.2
      micromol/L Ca(2+) with 1 mmol/L EGTA or 0.1 mmol/L EGTA, respectively, in an all
      or-none manner. These results suggest that Ca(2+) release induced by IP(3) is
      Ca(2+) dependent and is evoked in an all-or-none manner. 4. In the presence of
      the Ca(2+) ionophore A23187 (0.1 micromol/L) or the sarcoplasmic reticulum Ca(2+)
      ATPase inhibitor cyclopiazonic acid (1 micromol/L), the shortening of intact
      smooth muscle cells induced by increasing concentrations of ACh showed a graded
      response, but not an all-or-none response. 5. In conclusion, the results suggest
      that Ca(2+) release from Ca(2+) stores induced by IP(3) plays an important role
      in the all-or-none response of intact smooth muscle cells to ACh.

PMID- 18346177
TI  - Chronic ouabain treatment enhances cardiac myosin ATPase activity in rats.
AB  - 1. Chronic ouabain administration increases blood pressure and produces a
      positive inotropic effect. However, the temporal changes capable of affecting
      both arterial and ventricular pressures and myosin ATPase activity during the
      induced hypertension have not been determined. 2. The aim of the present study
      was to investigate the time-course of the induction of hypertension to define
      when changes occur in Wistar rats treated with 25 mg/kg per day, s.c., ouabain
      for 3, 7, 15 or 30 days. 3. In anaesthetized rats, diastolic blood pressure
      increased after 7 days treatment with ouabain and after 15 and 30 days treatment,
      increases were observed in systolic blood pressure, left ventricular systolic
      pressure and myosin ATPase activity. After 15 days treatment, heart rate (HR)
      also increased, but after 30 days treatment HR returned to control levels.
      However, only after 30 days treatment did the left ventricular positive and
      negative first derivatives of intraventricular pressure (dP/dt(max) and
      dP/dt(min), respectively) increase. Increased arterial and left ventricular
      systolic pressures and myosin ATPase activity observed after 15 days treatment
      maintained similar levels as those after 30 days treatment. 4. The results
      suggest that changes in arterial and left ventricular pressures, HR and myosin
      ATPase activity induced by chronic ouabain treatment are time dependent,
      increasing after 15 days treatment. After 30 days treatment, the increase in
      systolic and diastolic arterial and ventricular pressures remained stable, as did
      inotropism. Normalization of HR after 30 days treatment suggests that during the
      period from Day 16 to Day 30 ouabain-induced hypertension is dependent, at least
      in part, on increased sympathetic activity.

PMID- 18346178
TI  - Inhibition of ADP-induced platelet aggregation by clopidogrel is related to
      CYP2C19 genetic polymorphisms.
AB  - 1. Clopidogrel is one of the most important antithrombotic drugs but has
      different efficacies in different populations. The aim of the present study was
      to evaluate the contribution of CYP2C19 genetic polymorphisms to the inhibition
      of ADP-induced platelet aggregation by clopidogrel in healthy Chinese volunteers.
      2. Eighteen healthy male volunteers (six CYP2C19*1/CYP2C19*1, six
      CYP2C19*1/CYP2C19*2and*3 and six CYP2C19*2/CYP2C19*2and*3) were enrolled in the
      study. Each subject took 300 mg clopidogrel on the first day and then 75 mg once
      daily for 2 consecutive days. Blood samples were taken to measure ADP-induced
      platelet aggregation at baseline and 4, 24 and 72 h after administration of the
      first dose of clopidogrel. 3. There were significant decrease in 2 and 5
      micromol/L ADP-induced platelet aggregation at 4, 24 and 72 h after clopidogrel
      among the three CYP2C19 genotypes compared with baseline (P < 0.001). The change
      in 5 micromol/L ADP-induced platelet aggregation in subjects with the
      CYP2C19*1/CYP2C19*1 genotype was greater than that in subjects with the
      CYP2C19*2/CYP2C19*2and*3 genotype at 4 h (49.0 +/- 15.5 vs 29.7 +/- 17.4%,
      respectively; P = 0.029), 24 h (48.7 +/- 20.5 vs 25.0 +/- 17.6%, respectively; P
      = 0.035) and 72 h (45.5 +/- 15.2 vs 26.5 +/- 15.8%, respectively; P = 0.030)
      after clopidogrel administration. 4. In conclusion, CYP2C19*2 and CYP2C19*3
      genetic polymorphisms reduced clopidogrel inhibition of ADP-induced platelet
      aggregation, with the degree of inhition dependent on the genetic polymorphism
      present.

PMID- 18346179
TI  - Cardioprotection by L-glutamate during postischaemic reperfusion: reduced infarct
      size and enhanced glycogen resynthesis in a rat insulin-free heart model.
AB  - 1. Previously, we found that administration of high-dose L-glutamate during
      postischaemic reperfusion improves haemodynamic recovery and enhances glycogen
      resynthesis. In the present study, we investigated whether the same effect occurs
      in an insulin-free model and whether glutamate administration reduces infarct
      size. Further, we studied whether the cardioprotective effect of glutamate
      depends on preserved glutamate transamination and K(ATP) channel activity. 2. In
      a rat isolated, insulin-free, perfused heart model, we compared the effects of
      administration of L-glutamate (10 mmol/L) during either 45 min no-flow regional
      ischaemia plus 120 min reperfusion or reperfusion alone on infarct size and left
      ventricular (LV) recovery. The effect of glutamate on glycogen metabolism was
      studied in a model of 30 min global no-flow ischaemia and 60 min reperfusion. In
      both models, the effects of inhibition of glutamate transamination and K(ATP)
      channel activity were examined by adding amino-oxyacetate (an aminotransferase
      inhibitor; 0.1 mmol/L) and glibenclamide (a K(ATP) blocker; 10 mmol/L),
      respectively. 3. Administration of L-glutamate reduced infarct size by 60% (P <
      0.01) and improved postischaemic LV function (developed pressure and rate
      pressure product; P < 0.05). L-Glutamate increased glycogen content after 60 min
      reperfusion by 65% (P < 0.01). Amino-oxyacetate, as well as glibenclamide,
      abolished the glutamate-mediated reduction in infarct size, haemodynamic
      improvement and glycogen resynthesis during reperfusion. 4. In conclusion, L
      glutamate administration from the start of postischaemic reperfusion exerts
      cardioprotective effects, including reduced infarct size, improved haemodynamic
      recovery and enhanced glycogen resynthesis. These effects depend on preserved
      transamination of glutamate and K(ATP) channel activity, but not on insulin
      administration.

PMID- 18346180
TI  - Increased cardiac sympathetic drive and reduced vagal modulation following
      endothelin receptor antagonism in healthy conscious rats.
AB  - 1. The present study evaluated changes in autonomic control of the cardiovascular
      system in conscious rats following blockade of endothelin (ET) receptors with
      bosentan. 2. Rats were treated with bosentan or vehicle (5% gum arabic) for 7
      days by gavage. 3. Baseline heart rate (HR) was higher in the bosentan-treated
      group compared with the control group (418 +/- 5 vs 357 +/- 4 b.p.m.,
      respectively; P < 0.001). This baseline tachycardia was associated with a lower
      baroreflex sensitivity of the bradycardiac and tachycardiac responses in the
      bosentan-treated group compared with the control group. Sequential blockade of
      the parasympathetic and sympathetic autonomic nervous system with methylatropine
      and propranolol showed a higher intrinsic HR in the bosentan-treated group
      compared with the control group (411 +/- 5 vs 381 +/- 4 b.p.m., respectively; P <
      0.05). This was accompanied by a higher cardiac sympathetic tone (31 +/- 1 vs 13
      +/- 1%, respectively; P < 0.01) and a lower vagal parasympathetic tone (69 +/- 2
      vs 87 +/- 2%, respectively; P < 0.01) in the bosentan-treated group compared with
      the control group. Variance and high-frequency oscillations of pulse interval
      (PI) variability in absolute and normalized units were lower in the bosentan
      treated group than in the control group. Conversely, low-frequency (LF)
      oscillations of PI variability in absolute and normalized units, as well as
      variance and LF oscillations of systolic arterial pressure variability, were
      greater in the bosentan-treated group than the control group. 4. Overall, the
      data indicate an increased cardiac sympathetic drive, as well as lower vagal
      parasympathetic activity and baroreflex sensitivity, in conscious rats after
      chronic blockade of ET receptors with bosentan.

PMID- 18346181
TI  - A second case of dermatitis herpetiformis and cutaneous T-cell lymphoma.

PMID- 18346182
TI  - Treatment assessment by monitoring parasite load in skin biopsies from patients
      with cutaneous leishmaniasis, using quantitative nucleic acid sequence-based
      amplification.
AB  - BACKGROUND: Current diagnostic methods for cutaneous leishmaniasis (CL) have low
      sensitivity or are not useful for treatment follow-up. We previously described
      the quantitative nucleic acid sequence-based amplification (QT-NASBA) method as a
      sensitive and specific assay for detection and quantification of Leishmania
      parasites in skin biopsies. This assay could be a valuable instrument for
      monitoring response to treatment of CL and identifying treatment failures at an
      early stage. AIM: QT-NASBA results of skin biopsies at the end and 6 weeks after
      treatment from patients with proven CL on various treatment regimens were
      compared with clinical outcome. METHODS: The QT-NASBA assay measured the parasite
      load in skin biopsies before, at the end and 6 weeks after treatment. The results
      were compared with treatment outcome (clinical cure, delayed healing response or
      treatment failure) up to 6 months after treatment. RESULTS: In total, 137 skin
      biopsies were obtained from 53 patients. A positive QT-NASBA result 6 weeks after
      treatment was significantly associated with treatment failure/delayed healing up
      to 6 months (P < 0.001). The positive predictive value (PPV) was 100% and the
      negative predictive value (NPV) was 92% (95% CI 82-100%). QT-NASBA results at the
      end of treatment and clinical outcome showed a less significant association (P <
      0.05), with a PPV of 46% (95% CI 16-75% and an NPV of 89% (95% CI 79-99%).
      CONCLUSIONS: The QT-NASBA assay is a useful instrument to monitor parasite load
      in skin biopsies of patients with CL 6 weeks after treatment and can help to
      predict clinical outcome.

PMID- 18346183
TI  - Sebaceous gland hyperplasia, human immunodeficiency virus and highly active anti
      retroviral therapy.

PMID- 18346184
TI  - Efficacy of recombinant adenovirus-mediated double suicide gene therapy in human
      keloid fibroblasts.
AB  - BACKGROUND: The recombinant adenovirus-mediated double suicide gene CDglyTK has
      been widely used for gene therapy of cancer. The biological behaviour of keloids
      is similar to that of cancer, in that they may extend beyond the site of injury,
      and do not subside. There are no effective strategies available for keloid
      therapy. Gene therapy is gaining greater importance in the field of plastic
      surgery, and the CDglyTK double suicide gene/prodrug system has been receiving
      greater attention. AIM: To show the lethal and bystander effects of a double
      suicide gene in keloid fibroblasts. Bcl-2 and BAX play an important role in the
      apoptosis induced by the double suicide gene. METHODS: Recombinant adenovirus
      expression CDglyTK suicide genes were constructed using the modified AdEasy
      system. The lethal and bystander effects were measured after 48 h using the MTT
      assay. The morphological changes in fibroblasts were detected by haematoxylin and
      eosin staining, and apoptosis was detected by the terminal dUTP nick-end
      labelling assay. Bcl-2 and BAX were detected by immunohistochemistry and
      quantitative real-time PCR. RESULTS: CDglyTK could be constructed easily and
      relatively quickly. The lethal and bystander effects of CDglyTK were marked in
      keloid fibroblasts. Apoptosis was one of the main processes leading to fibroblast
      death in keloids, and Bcl-2 and BAX played an important role in the process of
      apoptosis. CONCLUSION: Together, the results support the notion that recombinant
      adenovirus-mediated CDglyTK double suicide gene therapy is effective in
      destroying keloid fibroblasts and provide a sound scientific rationale for keloid
      trials in vivo.

PMID- 18346185
TI  - Meta-analysis: remission and response from control arms of randomized trials of
      biological therapies for active luminal Crohn's disease.
AB  - BACKGROUND: Remission and response are the main outcomes to evaluate the efficacy
      of new treatments for Crohn's disease (CD). AIM: To explain variation of
      remission and response rates in active luminal CD. METHODS: We studied control
      patients from trials of biological therapies through articles retrieved by
      MEDLINE search (from 1997 to 2007) and by bibliography review. Thousand nine
      hundred and thirteen control patients from 28 trials were identified; data were
      extracted by three independent observers and pooled by DerSimonian and Laird
      random effect model; factors influencing remission and clinical response were
      explored by metaregression for aggregated data. RESULTS: The pooled control rates
      of remission and response were 17% and 33%, respectively, both with significant
      heterogeneity among studies (P < 0.0001). At metaregression, the time of primary
      outcome evaluation was associated with remission, whereas the trial's criteria
      for defining response and publication year were predictors of response. CDAI
      score, CRP levels or other clinical variables related with disease activity or
      concomitant medications were not significant factors. CONCLUSIONS: Populations
      used as 'add-on' treatment comparator in trials of biological therapies for
      active luminal CD are poorly characterized and outcomes are heterogeneous.
      Planning of future trials will require better description of patients and
      concomitant therapies, blinding of outcome assessors and homogeneous criteria of
      outcome definition.

PMID- 18346186
TI  - Safety, tolerability, and efficacy of pegylated-interferon alfa-2a plus ribavirin
      in HCV-related decompensated cirrhotics.
AB  - BACKGROUND: Pretransplantation clearance of hepatitis C virus (HCV)-RNA reduces
      the risk of HCV recurrence after transplantation. Furthermore, a sustained
      virological response could reduce disease progression and slow clinical
      deterioration in nontransplanted patients. AIM: To evaluate the safety,
      tolerability and efficacy of pegylated-interferon (PEG-IFN) alfa-2a plus
      ribavirin therapy in HCV-related decompensated cirrhotics. METHODS: Twenty HCV
      related decompensated cirrhotics (44-67 years, 12 males, six Child-Pugh score A,
      14 Child-Pugh score B, all with genotype 1b) were enrolled into the study.
      Treatment with PEG-IFN alfa-2a (135 microg, once a week) plus ribavirin (1000
      1200 mg/day) was commenced. A 48-week treatment was planned in patients who had
      early virological response. RESULTS: Treatment was stopped in 8 (40%) patients.
      The remaining 12 (60%) patients completed 48 weeks of therapy; nine (45%) of them
      obtained end-of-therapy virological response and six (30%) of them obtained
      sustained virological response. Living donor liver transplantation was performed
      in three (15%) patients. Eight (40%) and six (30%) patients needed to reduce PEG
      IFN alfa-2a and ribavirin dosages, respectively. No patient died during the
      follow-up period. CONCLUSION: PEG-IFN alfa-2a plus ribavirin therapy is safe,
      tolerable and efficacious in selected HCV-related decompensated cirrhotics.

PMID- 18346187
TI  - A national survey of acute hepatitis E in France.
AB  - BACKGROUND: Few data are available on the incidence, risk factors and
      contamination pathways involved in acute indigenous hepatitis E in developed
      countries. AIMS: To draw up an overall picture of hepatitis E cases, to confirm
      whether or not the majority of the cases were indigenous and to attempt to
      identify the risk factors and contamination pathways involved in hepatitis E.
      METHODS: This study was performed in the framework of a national network (ANGH)
      including 96 participating centres. The 19 centres with at least one case of
      acute HEV reported a total number of 53 cases. RESULTS: A decreasing South-to
      North geographic gradient was observed. A nonspecific clinical profile was
      observed in many cases. Acute hepatitis E was of indigenous origin in 90% of the
      patients. The most relevant and/or frequent possible risk factors among the 47
      indigenous metropolitan cases were water consumption from a personal water
      supply, uncooked shellfish consumption and the recent acquisition of a pet pig.
      CONCLUSIONS: This national survey confirmed that acute indigenous hepatitis E is
      an emerging disease in developed countries such as France, and suggests that
      various risk factors are responsible for acute indigenous hepatitis E
      contamination in non-endemic countries.

PMID- 18346188
TI  - The oomycete response gene LURP1 is required for defense against Hyaloperonospora
      parasitica in Arabidopsis thaliana.
AB  - LURP1 is a member of the LURP cluster and the PR1 regulon, two previously defined
      sets of co-expressed Arabidopsis thaliana genes that share a pronounced
      upregulation in response to infections by the pathogenic oomycete
      Hyaloperonospora parasitica. LURP1 shows the most extreme transcriptional
      inducibility by H. parasitica of all LURP and PR1 regulon genes. Using insertion
      mutants we found that LURP1 is required for full basal defense to H. parasitica
      and resistance to this pathogen mediated by the R-proteins RPP4 and RPP5. The
      LURP1 protein shows no obvious similarity to proteins of known molecular
      function. We identified a 39-bp region of the LURP1 promoter that mediates
      reporter gene expression in response to H. parasitica and salicylic acid. This
      promoter region contains a W box motif, W(LURP1), that interacts in vitro with
      nuclear factors producing two separate DNA-binding patterns. W(LURP1)-related
      sequences are strongly enriched in the promoters of the PR1 regulon, suggesting a
      role for this motif in the coordinated expression of genes inducible by H.
      parasitica and related defense conditions.

PMID- 18346189
TI  - AGL23, a type I MADS-box gene that controls female gametophyte and embryo
      development in Arabidopsis.
AB  - MADS-box transcription factors are key regulators of plant developmental
      processes. While the function of MIKC (type II) MADS-box genes has been
      intensively studied, only limited data are available for the other more recently
      identified classes of MADS-box genes, despite these latter comprising more than
      60% of the Arabidopsis MADS-box gene family. Here we describe the function of
      AGL23, an Arabidopsis type I MADS-box gene belonging to the Malpha subfamily. We
      show that AGL23 plays an important role during development of the female
      gametophyte and embryo. The agl23-1 mutant forms a functional megaspore. However,
      at this stage female gametophyte development is arrested and the megaspore
      persists during subsequent phases of ovule development. Despite the incomplete
      penetrance of the female gametophyte defect, plants homozygous for the agl23-1
      mutation were never identified. Analysis of developing seeds showed that embryos
      homozygous for the agl23-1 allele are albino and unable to give rise to viable
      plants. Electron microscopy analysis revealed that this phenotype is due to the
      absence of chloroplasts, strongly suggesting that AGL23 is involved in
      controlling the biogenesis of organelles during embryo development.

PMID- 18346190
TI  - Interplay of miR164, CUP-SHAPED COTYLEDON genes and LATERAL SUPPRESSOR controls
      axillary meristem formation in Arabidopsis thaliana.
AB  - Aerial architecture in higher plants is established post-embryonically by the
      inception of new meristems in the axils of leaves. These axillary meristems
      develop into side shoots or flowers. In Arabidopsis, the NAC domain transcription
      factors CUP SHAPED COTYLEDON1 (CUC1), CUC2 and CUC3 function redundantly in
      initiating the shoot apical meristem and establishing organ boundaries.
      Transcripts of CUC1 and CUC2 are targeted for degradation by miR164. In this
      study, we show that cuc3-2 mutants are impaired in axillary meristem initiation.
      Overexpression of miR164 in the cuc3-2 mutant caused an almost complete block of
      axillary meristem formation. Conversely, mir164 mutants and plants harbouring
      miR164-resistant alleles of CUC1 or CUC2 developed accessory buds in leaf axils.
      Collectively, these experiments reveal that, in addition to CUC3, redundant
      functions of CUC1 and CUC2 as well as miR164 regulation are required for the
      establishment of axillary meristems. Studies on LAS transcript accumulation in
      mir164 triple mutants and cuc3-2 plants overexpressing miR164 suggest that
      regulation of axillary meristem formation by miR164 is mediated through CUC1 and
      CUC2, which in turn regulate LAS.

PMID- 18346191
TI  - Identification of major lysine residues of S(3)-RNase of Petunia inflata involved
      in ubiquitin-26S proteasome-mediated degradation in vitro.
AB  - S-RNase-based self-incompatibility has been identified in three flowering plant
      families, including the Solanaceae, and this self/non-self recognition mechanism
      between pollen and pistil is controlled by two polymorphic genes at the S-locus,
      S-RNase and S-locus F-box (SLF). S-RNase is produced in the pistil and taken up
      by pollen tubes in a non-S-haplotype-specific manner. How an allelic product of
      SLF interacts with self and non-self S-RNases to result in growth inhibition of
      self pollen tubes is not completely understood. One model predicts that SLF
      targets non-self S-RNases for ubiquitin/26S proteasome-mediated degradation,
      thereby only allowing self S-RNase to exert cytotoxic activity inside a pollen
      tube. To test this model, we studied whether any of the 20 lysine residues in
      S(3)-RNase of Petunia inflata might be targets for ubiquitination. We identified
      six lysines near the C-terminus for which mutation to arginine significantly
      reduced ubiquitination and degradation of the mutant S(3)-RNase, GST:S(3)-RNase
      (K141-164R) in pollen tube extracts. We further showed that GST:S(3)-RNase (K141
      164R) and GST:S(3)-RNase had similar RNase activity, suggesting that their
      degradation was probably not caused by an ER-associated protein degradation
      pathway that removes mis-folded proteins. Finally, we showed that PiSBP1 (P.
      inflata S-RNase binding protein 1), a potential RING-HC subunit of the PiSLF (P.
      inflata SLF)-containing E3-like complex, could target S-RNase for ubiquitination
      in vitro. All these results suggest that ubiquitin/26S proteasome-dependent
      degradation of S-RNase may be an integral part of the S-RNase-based self
      incompatibility mechanism.

PMID- 18346192
TI  - Generation of a 3D indexed Petunia insertion database for reverse genetics.
AB  - BLAST searchable databases containing insertion flanking sequences have
      revolutionized reverse genetics in plant research. The development of such
      databases has so far been limited to a small number of model species and normally
      requires extensive labour input. Here we describe a highly efficient and widely
      applicable method that we adapted to identify unique transposon-flanking genomic
      sequences in Petunia. The procedure is based on a multi-dimensional pooling
      strategy for the collection of DNA samples; up to thousands of different
      templates are amplified from each of the DNA pools separately, and knowledge of
      their source is safeguarded by the use of pool-specific (sample) identification
      tags in one of the amplification primers. All products are combined into a single
      sample that is subsequently used as a template for unidirectional pyrosequencing.
      Computational analysis of the clustered sequence output allows automatic
      assignment of sequences to individual DNA sources. We have amplified and analysed
      transposon-flanking sequences from a Petunia transposon insertion library of 1000
      individuals. Using 30 DNA isolations, 70 PCR reactions and two GS20 sequencing
      runs, we were able to allocate around 10 000 transposon flanking sequences to
      specific plants in the library. These sequences have been organized in a database
      that can be BLAST-searched for insertions into genes of interest. As a proof of
      concept, we have performed an in silico screen for insertions into members of the
      NAM/NAC transcription factor family. All in silico-predicted transposon
      insertions into members of this family could be confirmed in planta.

PMID- 18346193
TI  - LeCTR2, a CTR1-like protein kinase from tomato, plays a role in ethylene
      signalling, development and defence.
AB  - Arabidopsis AtCTR1 is a Raf-like protein kinase that interacts with ETR1 and ERS
      and negatively regulates ethylene responses. In tomato, several CTR1-like
      proteins could perform this role. We have characterized LeCTR2, which has
      similarity to AtCTR1 and also to EDR1, a CTR1-like Arabidopsis protein involved
      in defence and stress responses. Protein-protein interactions between LeCTR2 and
      six tomato ethylene receptors indicated that LeCTR2 interacts preferentially with
      the subfamily I ETR1-type ethylene receptors LeETR1 and LeETR2, but not the NR
      receptor or the subfamily II receptors LeETR4, LeETR5 and LeETR6. The C-terminus
      of LeCTR2 possesses serine/threonine kinase activity and is capable of auto
      phosphorylation and phosphorylation of myelin basic protein in vitro.
      Overexpression of the LeCTR2 N-terminus in tomato resulted in altered growth
      habit, including reduced stature, loss of apical dominance, highly branched
      inflorescences and fruit trusses, indeterminate shoots in place of determinate
      flowers, and prolific adventitious shoot development from the rachis or rachillae
      of the leaves. Expression of the ethylene-responsive genes E4 and chitinase B was
      upregulated in transgenic plants, but ethylene production and the level of mRNA
      for the ethylene biosynthetic gene ACO1 was unaffected. The leaves and fruit of
      transgenic plants also displayed enhanced susceptibility to infection by the
      fungal pathogen Botrytis cinerea, which was associated with much stronger
      induction of pathogenesis-related genes such as PR1b1 and chitinase B compared
      with the wild-type. The results suggest that LeCTR2 plays a role in ethylene
      signalling, development and defence, probably through its interactions with the
      ETR1-type ethylene receptors of subfamily I.

PMID- 18346194
TI  - Heteromeric K+ channels in plants.
AB  - Voltage-gated potassium channels of plants are multimeric proteins built of four
      alpha-subunits. In the model plant Arabidopsis thaliana, nine genes coding for K+
      channel alpha-subunits have been identified. When co-expressed in heterologous
      expression systems, most of them display the ability to form heteromeric K+
      channels. Till now it was not clear whether plants use this potential of
      heteromerization to increase the functional diversity of potassium channels.
      Here, we designed an experimental approach employing different transgenic plant
      lines that allowed us to prove the existence of heteromeric K+ channels in
      plants. The chosen strategy might also be useful for investigating the activity
      and function of other multimeric channel proteins like, for instance, cyclic
      nucleotide gated channels, tandem-pore K+ channels and glutamate receptor
      channels.

PMID- 18346195
TI  - Lindernia brevidens: a novel desiccation-tolerant vascular plant, endemic to
      ancient tropical rainforests.
AB  - A particular adaptation to survival under limited water availability has been
      realized in the desiccation-tolerant resurrection plants, which tend to grow in a
      habitat with seasonal rainfall and long dry periods. One of the best-studied
      examples is Craterostigma plantagineum. Here we report an unexpected finding:
      Lindernia brevidens, a close relative of C. plantagineum, exhibits desiccation
      tolerance, even though it is endemic to the montane rainforests of Tanzania and
      Kenya, where it never experiences seasonal dry periods. L. brevidens has been
      found exclusively in two fragments of the ancient Eastern Arc Mountains, which
      were protected from the devastating Pleistocene droughts by the stable Indian
      Ocean temperature. Analysis of the microhabitat reveals that L. brevidens is
      found in the same habitat as hygrophilous plant species, which further indicates
      that the plant never dries out completely. The objective of this investigation
      was to address whether C. plantagineum and L. brevidens have desiccation-related
      pathways in common, or whether L. brevidens has acquired novel pathways. A third,
      closely related, desiccation-sensitive species, Lindernia subracemosa, has been
      included for comparison. Mechanisms that confer cellular protection during
      extreme water loss are well conserved between C. plantagineum and L. brevidens,
      including the interconversion of 2-octulose to sucrose within the two desiccation
      tolerant species. Furthermore, transcriptional control regions of desiccation
      related genes belonging to the late embryogenesis abundant (LEA) protein family
      are also highly conserved. We propose that L. brevidens is a neoendemic species
      that has retained desiccation tolerance through genome stability, despite
      tolerance being superfluous to environmental conditions.

PMID- 18346196
TI  - The redox switch of gamma-glutamylcysteine ligase via a reversible monomer-dimer
      transition is a mechanism unique to plants.
AB  - In plants, the first committed enzyme for glutathione biosynthesis, gamma
      glutamylcysteine ligase (GCL), is under multiple controls. The recent elucidation
      of GCL structure from Brassica juncea (BjGCL) has revealed the presence of two
      intramolecular disulfide bridges (CC1, CC2), which both strongly impact on GCL
      activity in vitro. Here we demonstrate that cysteines of CC1 are confined to
      plant species from the Rosids clade, and are absent in other plant families.
      Conversely, cysteines of CC2 involved in the monomer-dimer transition in BjGCL
      are not only conserved in the plant kingdom, but are also conserved in the
      evolutionarily related alpha- (and some gamma-) proteobacterial GCLs. Focusing on
      the role of CC2 for GCL redox regulation, we have extended our analysis to all
      available plant (31; including moss and algal) and related proteobacterial GCL
      (46) protein sequences. Amino acids contributing to the homodimer interface in
      BjGCL are highly conserved among plant GCLs, but are not conserved in related
      proteobacterial GCLs. To probe the significance of this distinction, recombinant
      GCLs from Nicotiana tabacum (NtGCL), Agrobacterium tumefaciens (AtuGCL, alpha
      proteobacteria) and Xanthomonas campestris (XcaGCL, gamma-proteobacteria) were
      analyzed for their redox response. As expected, NtGCL forms a homodimer under
      oxidizing conditions, and is activated more than threefold. Conversely,
      proteobacterial GCLs remain monomeric under oxidizing and reducing conditions,
      and their activities are not inhibited by DTT, despite the presence of CC2. We
      conclude that although plant GCLs are evolutionarily related to proteobacterial
      GCLs, redox regulation of their GCLs via CC2-dependent dimerization has been
      acquired later in evolution, possibly as a consequence of compartmentation in the
      redox-modulated plastid environment.

PMID- 18346197
TI  - Identification of indole glucosinolate breakdown products with antifeedant
      effects on Myzus persicae (green peach aphid).
AB  - The cleavage of glucosinolates by myrosinase to produce toxic breakdown products
      is a characteristic insect defense of cruciferous plants. Although green peach
      aphids (Myzus persicae) are able to avoid most contact with myrosinase when
      feeding from the phloem of Arabidopsis thaliana, indole glucosinolates are
      nevertheless degraded during passage through the insects. A defensive role for
      indole glucosinolates is suggested by the observation that atr1D mutant plants,
      which overproduce indole glucosinolates, are more resistant to M. persicae,
      whereas cyp79B2 cyp79B3 double mutants, which lack indole glucosinolates, succumb
      to M. persicae more rapidly. Indole glucosinolate breakdown products, including
      conjugates formed with ascorbate, glutathione and amino acids, are elevated in
      the honeydew of M. persicae feeding from atr1D mutant plants, but are absent when
      the aphids are feeding on cyp79B2 cyp79B3 double mutants. M. persicae feeding
      from wild-type plants and myrosinase-deficient tgg1 tgg2 double mutants excrete a
      similar profile of indole glucosinolate-derived metabolites, indicating that the
      breakdown is independent of these foliar myrosinases. Artificial diet experiments
      show that the reaction of indole-3-carbinol, a breakdown product of indol-3
      ylmethylglucosinolate, with ascorbate, glutathione and cysteine produces
      diindolylmethylcysteines and other conjugates that have antifeedant effects on M.
      persicae. Therefore, the post-ingestive breakdown of indole glucosinolates
      provides a defense against herbivores such as aphids that can avoid glucosinolate
      activation by plant myrosinases.

PMID- 18346198
TI  - Androgens regulate neprilysin expression: role in reducing beta-amyloid levels.
AB  - Age-related testosterone depletion in men is a risk factor for Alzheimer's
      disease. Prior studies suggest that androgens affect Alzheimer's disease risk by
      regulating accumulation of beta-amyloid protein (Abeta) by an undefined
      mechanism. In this study, we investigated the role of the Abeta-catabolizing
      enzyme neprilysin (NEP) in this process. First, we observed that androgens
      positively regulate neural expression of NEP in adult male rats. Next, we
      investigated androgen regulatory effects on both NEP expression and Abeta levels
      using cultured hippocampal neurons and neuronally differentiated rat
      pheochromocytoma cell 12 with or without androgen receptor (AR).
      Dihydrotestosterone (DHT) induced a time-dependent increase in NEP expression.
      DHT also significantly decreased levels of Abeta in AR-expressing cells
      transfected with amyloid precursor protein, but did not affect levels of either
      full-length or non-amyloidogenic, soluble amyloid precursor protein. Importantly,
      the DHT induced decrease of Abeta was blocked by pharmacological inhibition of
      NEP. The DHT-mediated increase in NEP expression and decrease in Abeta levels
      were (i) not observed in rat pheochromocytoma cell 12 lacking AR and (ii) blocked
      in AR-expressing cells by the antagonists, cyproterone acetate and flutamide.
      Together, these findings suggest that androgen regulation of Abeta involves an AR
      dependent mechanism requiring up-regulation of the Abeta catabolizing enzyme NEP.

PMID- 18346199
TI  - D2 dopamine receptor expression and trafficking is regulated through direct
      interactions with ZIP.
AB  - We have used the yeast two-hybrid system to identify protein kinase C-zeta
      interacting protein (ZIP) as a novel interacting protein for the D(2) dopamine
      receptor (DAR). This interaction was identified by screening a rat brain cDNA
      library using the third intracellular loop of the D(2) DAR as bait. A partial
      length cDNA encoding ZIP was isolated and characterized as specifically
      interacting with the third intracellular loop of the D(2) DAR, but not with the
      third intracellular loops of other DAR subtypes. Biochemical confirmation of the
      ZIP-D(2) DAR interaction was obtained by expressing the full-length ZIP and D(2)
      DAR proteins in mammalian cells and demonstrating that they could be co
      immunoprecipitated. We further showed that ZIP and the D(2) DAR could be co
      immunoprecipitated from endogenous brain tissues. Immunohistochemical analyses
      further revealed that ZIP and the D(2) DAR were extensively co-localized within
      numerous neurons in various brain regions. ZIP exists as three protein isoforms
      of varying length, which are derived from alternative RNA splicing. All three
      isoforms were found to interact with the D(2) DAR, which allowed for the
      delineation of the receptor interacting domain to within 38 residues of ZIP.
      Functionally, over-expression of ZIP was found to result in decreased expression
      of the D(2) DAR with a corresponding decrease in receptor modulation of cAMP
      accumulation. Confocal microscopy revealed that ZIP over-expression also lead to
      an intracellular accumulation of D(2) DAR protein in lysosome compartments. These
      results suggest that ZIP can physically interact with the D(2) DAR leading to
      increased intracellular trafficking to lysosomes with subsequent down-regulation
      of receptor expression and function.

PMID- 18346200
TI  - Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from
      cytosolic phospholipase A2 in cortical neurons.
AB  - Increase in oxidative stress has been postulated to play an important role in the
      pathogenesis of a number of neurodegenerative diseases including Alzheimer's
      disease. There is evidence for involvement of amyloid-beta peptide (Abeta) in
      mediating the oxidative damage to neurons. Despite yet unknown mechanism, Abeta
      appears to exert action on the ionotropic glutamate receptors, especially the N
      methyl-D-aspartic acid (NMDA) receptor subtypes. In this study, we showed that
      NMDA and oligomeric Abeta(1-42) could induce reactive oxygen species (ROS)
      production from cortical neurons through activation of NADPH oxidase. ROS derived
      from NADPH oxidase led to activation of extracellular signal-regulated kinase
      1/2, phosphorylation of cytosolic phospholipase A(2)alpha (cPLA(2)alpha), and
      arachidonic acid (AA) release. In addition, Abeta(1-42)-induced AA release was
      inhibited by d(-)-2-amino-5-phosphonopentanoic acid and memantine, two different
      NMDA receptor antagonists, suggesting action of Abeta through the NMDA receptor.
      Besides serving as a precursor for eicosanoids, AA is also regarded as a
      retrograde messenger and plays a role in modulating synaptic plasticity. Other
      phospholipase A(2) products such as lysophospholipids can perturb membrane
      phospholipids. These results suggest an oxidative-degradative mechanism for
      oligomeric Abeta(1-42) to induce ROS production and stimulate AA release through
      the NMDA receptors. This novel mechanism may contribute to the oxidative stress
      hypothesis and synaptic failure that underline the pathogenesis of Alzheimer's
      disease.

PMID- 18346201
TI  - High temporal resolution of amino acid levels in rat nucleus accumbens during
      operant ethanol self-administration: involvement of elevated glycine in
      anticipation.
AB  - Capillary electrophoresis coupled with laser-induced fluorescence detection (CE
      LIF) provides 15-s temporal resolution of amino acid levels in microdialysate,
      which, for the first time, allows almost real time measurement of changes during
      episodes of behavior. We trained Sprague-Dawley rats to self-administer either
      10% ethanol-containing gelatin or non-alcoholic gelatin in a typical operant
      chamber. After rats reached stable daily levels of responding, microdialysis
      probes were inserted into nucleus accumbens and samples were collected before,
      during and after operant sessions with on-line analysis via CE-LIF. During the
      first 15 min of the operant session, there was a significant increase in taurine
      that correlated with the amount of ethanol consumed (R(2)=0.81) but no change in
      rats responding for plain gel. There were large, consistent increases in glycine
      in both the ethanol and plain gel groups which correlated with the amount of gel
      consumed. A smaller increase was observed in rats with free non-operant access to
      plain gel compared to the increase seen with the same amount of gel consumed
      under operant conditions. When rats were given a time out after each delivery of
      gel in the operant protocol, the greatest increase of glycine was obtained with
      the longest time out period. Thus, increases in glycine in nucleus accumbens
      appear to be related to anticipation of reinforcement.

PMID- 18346202
TI  - Immunoproteasome responds to injury in the retina and brain.
AB  - It is well known that immunoproteasome generates peptides for MHC Class I
      occupancy and recognition by cytotoxic T lymphocytes (CTL). The present study
      focused on evidence for alternative roles for immunoproteasome. Retina and brain
      were analyzed for expression of immunoproteasome subunits using
      immunohistochemistry and western blotting under normal conditions and after
      injury/stress induced by CTL attack on glia (brain) or neurons (retina). Normal
      retina expressed substantial levels of immunoproteasome in glia, neurons, and
      retinal pigment epithelium. The basal level of immunoproteasome in retina was two
      fold higher than in brain; CTL-induced retinal injury further up-regulated
      immunoproteasome expression. Immunoproteasome up-regulation was also observed in
      injured brain and corresponded with expression in Purkinje cells, microglia,
      astrocytes, and oligodendrocytes. These results suggest that the normal
      environment of the retina is sufficiently challenging to require on-going
      expression of immunoproteasome. Further, immunoproteasome up-regulation with
      retinal and brain injury implies a role in neuronal protection and/or repair of
      damage.

PMID- 18346203
TI  - Distinct changes in neuronal and astrocytic amino acid neurotransmitter
      metabolism in mice with reduced numbers of synaptic vesicles.
AB  - The relations between glutamate and GABA concentrations and synaptic vesicle
      density in nerve terminals were examined in an animal model with 40-50% reduction
      in synaptic vesicle numbers caused by inactivation of the genes encoding synapsin
      I and II. Concentrations and synthesis of amino acids were measured in extracts
      from cerebrum and a crude synaptosomal fraction by HPLC and (13)C nuclear
      magnetic resonance spectroscopy (NMRS), respectively. Analysis of cerebrum
      extracts, comprising both neurotransmitter and metabolic pools, showed decreased
      concentration of GABA, increased concentration of glutamine and unchanged
      concentration of glutamate in synapsin I and II double knockout (DKO) mice. In
      contrast, both glutamate and GABA concentrations were decreased in crude
      synaptosomes isolated from synapsin DKO mice, suggesting that the large metabolic
      pool of glutamate in the cerebral extracts may overshadow minor changes in the
      transmitter pool. (13)C NMRS studies showed that the changes in amino acid
      concentrations in the synapsin DKO mice were caused by decreased synthesis of
      GABA (20-24%) in cerebral neurons and increased synthesis of glutamine (36%) in
      astrocytes. In a crude synaptosomal fraction, the glutamate synthesis was reduced
      (24%), but this reduction could not be detected in cerebrum extracts. We suggest
      that lack of synaptic vesicles causes down-regulation of neuronal GABA and
      glutamate synthesis, with a concomitant increase in astrocytic synthesis of
      glutamine, in order to maintain normal neurotransmitter concentrations in the
      nerve terminal cytosol.

PMID- 18346204
TI  - In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in
      vitro mutagenesis defines the requisite binding sites for downstream Akt
      activation.
AB  - Axl is a receptor tyrosine kinase implicated in cell survival following growth
      factor withdrawal and other stressors. The binding of Axl's ligand, growth arrest
      specific protein 6 (Gas6), results in Axl autophosphorylation, recruitment of
      signaling molecules, and activation of downstream survival pathways. Pull-down
      assays and immunoprecipitations using wildtype and mutant Axl transfected cells
      determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2)
      at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two
      pYXXM sites (pY779 and pY821). Also, p85 can indirectly bind to Axl via an
      interaction between p85's second proline-rich region and the N-terminal SH3
      domain of Grb2. Further, Grb2 and p85 can compete for binding at the pY821VNM
      site. Gas6-stimulation of Axl-transfected COS7 cells recruited activated PI3
      kinase and phosphorylated Akt. An interaction between Axl, p85 and Grb2 was
      confirmed in brain homogenates, enriched populations of O4+ oligodendrocytes, and
      O4- flow-through prepared from day 10 mouse brain, indicating that cells with
      active Gas6/Axl signal through Grb2 and the PI3 kinase/Akt pathways.

PMID- 18346205
TI  - FK506 binding protein 12 differentially accelerates fibril formation of wild type
      alpha-synuclein and its clinical mutants A30P or A53T.
AB  - Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's
      disease. We have previously shown that aggregation of alpha-SYN in vitro is
      accelerated by addition of FK506 binding proteins (FKBP) and that this effect can
      be counteracted by FK506, a specific inhibitor of these enzymes. In this paper,
      we investigated in detail the effect of FKBP12 on early aggregation and on fibril
      formation of wild-type, A53T and A30P alpha-SYN. FKBP12 has a much smaller effect
      on the fibril formation of these two clinical mutants alpha-SYN. Using an
      inactive enzyme, we were able to discriminate between catalytic and non-catalytic
      effects that differentially influence the two processes. A model explaining non
      linear concentration dependencies is proposed.

PMID- 18346206
TI  - Genetic inactivation of p62 leads to accumulation of hyperphosphorylated tau and
      neurodegeneration.
AB  - The signaling adapter p62 plays a coordinating role in mediating phosphorylation
      and ubiquitin-dependent trafficking of interacting proteins. However, there is
      little known about the physiologic role of this protein in brain. Here, we report
      age-dependent constitutive activation of glycogen synthase kinase 3beta, protein
      kinase B, mitogen-activated protein kinase, and c-Jun-N-terminal kinase in adult
      p62(-/-) mice resulting in hyperphosphorylated tau, neurofibrillary tangles, and
      neurodegeneration. Biochemical fractionation of p62(-/-) brain led to recovery of
      aggregated K63-ubiquitinated tau. Loss of p62 was manifested by increased
      anxiety, depression, loss of working memory, and reduced serum brain-derived
      neurotrophic factor levels. Our findings reveal a novel role for p62 as a
      chaperone that regulates tau solubility thereby preventing tau aggregation. This
      study provides a clear demonstration of an Alzheimer-like phenotype in a mouse
      model in the absence of expression of human genes carrying mutations in amyloid
      beta protein precursor, presenilin, or tau. Thus, these findings provide new
      insight into manifestation of sporadic Alzheimer disease and the impact of
      obesity.

PMID- 18346207
TI  - A novel calcium-binding protein is associated with tau proteins in tauopathy.
AB  - Tauopathies are a group of neurological disorders characterized by the presence
      of intraneuronal hyperphosphorylated and filamentous tau. Mutations in the tau
      gene have been found in kindred with tauopathy. The expression of the human tau
      mutant in transgenic mice induced neurodegeneration, indicating that tau plays a
      central pathological role. However, the molecular mechanism leading to tau
      mediated neurodegeneration is poorly understood. To gain insights into the role
      that tau plays in neurodegeneration, human tau proteins were immunoprecipitated
      from brain lysates of the tauopathy mouse model JNPL3, which develops
      neurodegeneration in age-dependent manner. In the present work, a novel EF-hand
      domain-containing protein was found associated with tau proteins in brain lysate
      of 12-month-old JNPL3 mice. The association between tau proteins and the novel
      identified protein appears to be induced by the neurodegeneration process as
      these two proteins were not found associated in young JNPL3 mice. Consistently,
      the novel protein co-purified with the pathological sarkosyl insoluble tau in
      terminally ill JNPL3 mice. Calcium-binding assays demonstrated that this protein
      binds calcium effectively. Finally, the association between tau and the novel
      calcium-binding protein is conserved in human and enriched in Alzheimer's disease
      brain. Taken together, the identification of a novel calcium-binding protein
      associated with tau protein in terminally ill tauopathy mouse model and its
      confirmation in human brain lysate suggests that this association may play an
      important physiological and/or pathological role.

PMID- 18346208
TI  - Temporal and functional dynamics of the transcriptome during nerve growth factor
      induced differentiation.
AB  - The rat pheochromocytoma cell line (PC12) is an extensively used model to study
      neuronal differentiation. The initial signaling cascades triggered by nerve
      growth factor (NGF) stimulation have been subject to thorough investigation and
      are well characterized. However, knowledge of temporal transcriptomal regulation
      during NGF-induced differentiation of PC12 cells remains far from complete. We
      performed a microarray study that characterized temporal and functional changes
      of the transcriptome during 4 subsequent days of differentiation of Neuroscreen-1
      PC12 cells. By analyzing the transcription profiles of 1595 NGF-regulated genes,
      we show a large diversity of transcriptional regulation in time. Also, we
      quantitatively identified 26 out of 243 predefined biological process and 30 out
      of 255 predefined molecular function classes that are specifically regulated by
      NGF. Combining the temporal and functional transcriptomal data revealed that NGF
      selectively exerts a temporally coordinated regulation of genes implicated in
      protein biosynthesis, intracellular signaling, cell structure, chromatin
      packaging and remodeling, intracellular protein traffic, mRNA transcription, and
      cell cycle. We will discuss how NGF-induced changes may modulate the
      transcriptional response to NGF itself during differentiation.

PMID- 18346209
TI  - Effects of chronic exercise on myocardial refractoriness: a study on isolated
      rabbit heart.
AB  - AIM: To determine whether chronic physical training increases atrial and
      ventricular refractoriness in isolated rabbit heart. METHODS: Trained rabbits
      were submitted to a protocol of treadmill running. The electrophysiological
      parameters of refractoriness investigated in an isolated heart preparation were:
      (1) atrial effective refractory period (AERP) and atrial functional refractory
      period and ventricular effective and functional refractory periods (VERP and
      VFRP) using the extrastimulus technique at four different pacing cycle lengths;
      (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi
      electrode plaque containing 256 electrodes and a spectral method were used to
      obtain the mean, maximum and minimum DF of VF. Sinus cycle length of the isolated
      hearts was determined as an electrophysiological parameter of training. In vivo
      heart rate, myocardial heat shock proteins (HSP60) and inducible nitric oxide
      synthase were also determined in some animals as electrophysiological and
      biochemical markers of training respectively. RESULTS: VERP and VFRP were longer
      in the trained group than in the control group. The mean DF of VF was lower in
      the trained group than in the control group. Despite the fact that training did
      not significantly modify the AERP, it tended to be longer in the trained group (P
      = 0.09). CONCLUSION: Training seems to increase the electrical stability of
      ventricular myocardium. As the electrophysiological modifications were exhibited
      in hearts not submitted to extrinsic nervous system or humoral influences, they
      are, at least in part, intrinsic modifications. These electrophysiological data
      also suggest that training could protect against reentrant ventricular
      arrhythmias.

PMID- 18346210
TI  - Spinal and supraspinal adaptations associated with balance training and their
      functional relevance.
AB  - Traditionally, balance training has been used to rehabilitate ankle injuries and
      postural deficits. Prospective studies have shown preventive effects with respect
      to ankle and knee joint injuries. Presently, balance training is not only applied
      for rehabilitation and prevention but also for improving motor performance,
      especially muscle power. The recent application of noninvasive
      electrophysiological and brain imaging techniques revealed insights into the
      central control of posture and the adaptations induced by balance training. This
      information is important for our understanding of the basic control and
      adaptation mechanisms and to conceptualize appropriate training programmes for
      athletes, elderly people and patients. The present review presents
      neurophysiological adaptations induced by balance training and their influence on
      motor behaviour. It emphasizes the plasticity of the sensorimotor system,
      particularly the spinal and supraspinal structures. The relevance of balance
      training is highlighted with respect to athletic performance, postural control
      within elderly people as well as injury prevention and rehabilitation.

PMID- 18346211
TI  - Significant inverse relationship between serum free T4 concentration and body
      mass index in euthyroid subjects: differences between smokers and nonsmokers.
AB  - OBJECTIVE: There are conflicting data regarding the relationship between thyroid
      function and body mass index (BMI) in euthyroid subjects, and it is uncertain
      whether tobacco smoking modifies this relationship. The objective of this study
      was to examine the relationships between thyroid function, BMI and smoking in
      euthyroid subjects. DESIGN: Linear regression models were used to examine the
      relationships between serum free T4, serum TSH, BMI and smoking in a cross
      sectional, community-based sample of 1853 euthyroid subjects in Busselton,
      Western Australia. RESULTS: There was a significant negative relationship between
      free T4 and BMI: after adjustment for age and sex, each 1 pmol/l increase in free
      T4 was associated with a decrease in BMI of 0.12 kg/m(2) (95% CI 0.06, 0.18; P <
      0.001). The mean BMI +/- SD of subjects in the highest quintile of free T4
      concentration was 24.4 +/- 3.5 kg/m(2), compared with 26.1 +/- 3.8 kg/m(2) for
      the lowest quintile. The relationship between free T4 and BMI was statistically
      significant (adjusted for age and sex) in subjects who had never smoked (P =
      0.001) and former smokers (P = 0.011), but not in current smokers (P = 0.77).
      There was no significant relationship between TSH and BMI: after adjustment for
      age and sex, each 1 mU/l increase in TSH was associated with an increase in BMI
      of 0.08 kg/m(2) (95% CI -0.16, 0.32; P = 0.53). CONCLUSIONS: In euthyroid
      subjects, small differences in free T4 are associated with differences in BMI.
      This relationship is not present in current smokers. We speculate that this may
      be relevant to weight changes associated with smoking cessation.

PMID- 18346212
TI  - Clinical insights into the safety and utility of the insulin tolerance test (ITT)
      in the assessment of the hypothalamo-pituitary-adrenal axis.
AB  - OBJECTIVE: The insulin tolerance test (ITT) is the gold standard for assessing GH
      and cortisol production in pituitary disease. However, areas of uncertainty
      remain regarding its safety in older people, the optimal duration of the test and
      its performance in insulin resistant states. Whether basal cortisol concentration
      can reliably predict an adequate adrenal response to hypoglycaemia remains to be
      determined. PATIENTS AND DESIGN: We performed a cross-sectional retrospective
      examination of 197 consecutive patients (mean age 41.8 +/- 16.4, range 13-76
      years) with pituitary disease who underwent the ITT over 18 months. The standard
      intravenous insulin dose administered was 0.15 units/kg body weight. Patients
      with acromegaly or with type 2 diabetes received 0.2 units/kg; those with basal
      cortisol < 100 nmol/l received 0.1 units/kg. RESULTS: Adequate hypoglycaemia
      (nadir glucose < 2.2 mmol/l) was achieved in 87% of patients, amongst whom 17%
      did not achieve peak cortisol until 120 min. There were no significant adverse
      events, even in those >or= 65 years. Of the 18 patients who had basal cortisol <
      100 nmol/l, 78% achieved adequate hypoglycaemia; 29% of those had an adequate
      peak cortisol response >or= 500 nmol/l. A receiver operating characteristics
      curve identified a basal cortisol of >or= 393 nmol/l to predict a normal peak
      cortisol response to hypoglycaemia. CONCLUSIONS: In specialized units, the ITT is
      safe even in elderly patients and those with hypocortisolaemia. The standard 90
      min. cut-off for the ITT misses one in six peak cortisol responses. Some patients
      with basal cortisol < 100 nmol/l had a normal cortisol response to hypoglycaemia.

PMID- 18346213
TI  - Identification of trafficking determinants for polytopic rhomboid proteases in
      Toxoplasma gondii.
AB  - Rhomboids (ROMs) constitute a family of polytopic serine proteases conserved
      throughout evolution. The obligate intracellular parasite Toxoplasma gondii
      possesses six genes coding for ROM-like proteases that are targeted to distinct
      subcellular compartments: TgROM1 localizes to regulated secretory organelles,
      micronemes, TgROM2 is present in the Golgi, while TgROM4 and TgROM5 are found in
      the pellicle of the parasite. The targeting mechanism/s of ROM proteins is an
      aspect that has not yet been assessed. The existence of TgROM family members
      localized to different subcellular compartments provides a convenient system to
      study their sorting mechanisms in a genetically tractable organism that possesses
      an elaborate secretory pathway and conserved trafficking machineries. In this
      study, we experimentally established the topology of TgROM1 and TgROM4 at the
      plasma membrane and applied domain-exchange and site-directed mutagenesis
      approaches to identify critical sorting determinants on the N-terminal cytosolic
      domains of TgROM2 and TgROM1 that confer their Golgi and post-Golgi
      localizations, respectively.

PMID- 18346214
TI  - btn1 affects endocytosis, polarization of sterol-rich membrane domains and
      polarized growth in Schizosaccharomyces pombe.
AB  - btn1, the Schizosaccharomyces pombe orthologue of the human Batten disease gene
      CLN3, exerts multiple cellular effects. As well as a role in vacuole pH
      homoeostasis, we now show that Btn1p is essential for growth at high
      temperatures. Its absence results in progressive defects at 37 degrees C that
      culminate in total depolarized growth and cell lysis. These defects are preceded
      by a progressive failure to correctly polarize sterol-rich domains after
      cytokinesis and are accompanied by loss of Myo1p localization. Furthermore, we
      found that in Sz. pombe, sterol spreading is linked to defective
      formation/polarization of F-actin patches and disruption of endocytosis and that
      these processes are aberrant in btn1Delta cells. Consistent with a role for Btn1p
      in polarized growth, Btn1p has an altered location at 37 degrees C and is
      retained in actin-dependent endomembrane structures near the cell poles or
      septum.

PMID- 18346215
TI  - Longevity-fertility trade-offs in the tephritid fruit fly, Anastrepha ludens,
      across dietary-restriction gradients.
AB  - Although it is widely known that dietary restriction (DR) not only extends the
      longevity of a wide range of species but also reduces their reproductive output,
      the interrelationship of DR, longevity extension and reproduction is not well
      understood in any organism. Here we address the question: 'Under what nutritional
      conditions do the longevity-enhancing effects resulting from food restriction
      either counteract, complement or reinforce the mortality costs of reproduction?
      To answer this question we designed a fine-grained DR study involving 4800
      individuals of the tephritid fruit fly, Anastrepha ludens, in which we measured
      sex-specific survival and daily reproduction in females in each of 20 different
      treatments (sugar : yeast ratios) plus 4 starvation controls. The database
      generated from this 3-year study consisted of approximately 100 000 life-days for
      each sex and 750 000 eggs distributed over the reproductive lives of 2400
      females. The fertility and longevity-extending responses were used to create
      contour maps (X-Y grid) that show the demographic responses (Z-axis) across
      dietary gradients that range from complete starvation to both ad libitum sugar
      only and ad libitum standard diet (3 : 1 sugar : yeast). The topographic
      perspectives reveal demographic equivalencies along nutritional gradients,
      differences in the graded responses of males and females, egg production costs
      that are sensitive to the interaction of food amounts and constituents, and
      orthogonal contours (equivalencies in longevity or reproduction) representing
      demographic thresholds related to both caloric content and sugar : yeast ratios.
      In general, the finding that lifespan and reproductive maxima occur at much
      different nutritional coordinates poses a major challenge for the use of food
      restriction (or a mimetic) in humans to improve health and extend longevity in
      humans.

PMID- 18346216
TI  - Identification and characterization of a Drosophila ortholog of WRN exonuclease
      that is required to maintain genome integrity.
AB  - The premature human aging Werner syndrome (WS) is caused by mutation of the RecQ
      family WRN helicase, which is unique in possessing also 3'-5' exonuclease
      activity. WS patients show significant genomic instability with elevated cancer
      incidence. WRN is implicated in restraining illegitimate recombination,
      especially during DNA replication. Here we identify a Drosophila ortholog of the
      WRN exonuclease encoded by the CG7670 locus. The predicted DmWRNexo protein shows
      conservation of structural motifs and key catalytic residues with human WRN
      exonuclease, but entirely lacks a helicase domain. Insertion of a piggyBac
      element into the 5' UTR of CG7670 severely reduces gene expression. DmWRNexo
      mutant flies homozygous for this insertional allele of CG7670 are thus severely
      hypomorphic; although adults show no gross morphological abnormalities, females
      are sterile. Like human WS cells, we show that the DmWRNexo mutant flies are
      hypersensitive to the topoisomerase I inhibitor camptothecin. Furthermore, these
      mutant flies show highly elevated rates of mitotic DNA recombination resulting
      from excessive reciprocal exchange. This study identifies a novel WRN ortholog in
      flies and demonstrates an important role for WRN exonuclease in maintaining
      genome stability.

PMID- 18346217
TI  - Impact of reduced insulin-like growth factor-1/insulin signaling on aging in
      mammals: novel findings.
AB  - Growth hormone deficiency or resistance resulting from spontaneous or
      experimentally produced mutations in laboratory mice delay aging and increase
      lifespan. Alterations in insulin-like growth factor-1 (IGF-1) and insulin
      signaling emerged as likely mechanisms linking growth hormone and aging, and
      increased longevity was reported in mice with selective deletion of IGF-1
      receptor in all tissues or insulin receptor in fat. Recent studies in mice with
      reduced IGF-1 levels or deletion of pregnancy-associated plasma protein-A, a
      protease that cleaves one of the IGF-1 binding proteins, strongly support the
      role of IGF-1 in the control of longevity. Reports of increased lifespan in mice
      with deletion of insulin receptor substrate (IRS) 1, reduced expression of IRS2,
      or selective deletion of IRS2 in the brain specifically implicate the IRS-PI3K
      Akt-Foxo signaling pathway (which is shared by IGF-1 and insulin) in the control
      of aging. These important novel findings also strengthen the evidence for
      evolutionary conservation of mechanisms regulating lifespan in worms, insects and
      mammals.

PMID- 18346218
TI  - Fine-scale adaptation in a clonal sea anemone.
AB  - Local adaptation in response to fine-scale spatial heterogeneity is well
      documented in terrestrial ecosystems. In contrast, in marine environments local
      adaptation has rarely been documented or rigorously explored. This may reflect
      real or anticipated effects of genetic homogenization, resulting from widespread
      dispersal in the sea. However, evolutionary theory predicts that for the many
      benthic species with complex life histories that include both sexual and asexual
      phases, each parental habitat patch should become dominated by the fittest and
      most competitive clones. In this study we used genotypic mapping to show that
      within headlands, clones of the sea anemone Actinia tenebrosa show restricted
      distributions to specific habitats despite the potential for more widespread
      dispersal. On these same shores we used reciprocal transplant experiments that
      revealed strikingly better performance of clones within their natal rather than
      foreign habitats as judged by survivorship, asexual fecundity, and growth. These
      findings highlight the importance of selection for fine-scale environmental
      adaptation in marine taxa and imply that the genotypic structure of populations
      reflects extensive periods of interclonal competition and site-specific
      selection.

PMID- 18346219
TI  - Q(St) meets the G matrix: the dimensionality of adaptive divergence in multiple
      correlated quantitative traits.
AB  - The Q(ST)-F(ST) comparison has become an increasingly common method for inferring
      adaptive quantitative trait divergence among populations. For cases in which
      there is divergence in multiple traits, most studies have applied the method by
      performing multiple univariate Q(ST)-F(ST) comparisons. However, because traits
      are often genetically correlated, such univariate analyses are likely to paint a
      simplified picture of adaptive divergence. Here we show how the multivariate
      analogue of Q(ST), F(STq), which accounts for genetic correlations among traits,
      can be used to supply a more detailed picture of multitrait divergence. We apply
      the method to naturally occurring genetic variation for a suite of sexually
      selected display traits in Drosophila serrata. The analyses suggest the operation
      of divergent multivariate selection that has influenced multiple independent axes
      of genetic variance in a sex-specific manner. Finally, we show how a comparison
      of the components of F(STq), the average within and among population genetic
      variance-covariance matrices, G(W) and G(B), can be used as an additional test of
      the null expectation of neutral divergence, and allows for an investigation of
      whether natural populations have diverged along major or minor axes of genetic
      variance.

PMID- 18346220
TI  - Genetic variation in wild and cultivated populations of the haploid-diploid red
      alga Gracilaria chilensis: how farming practices favor asexual reproduction and
      heterozygosity.
AB  - The extent of changes in genetic diversity and life-history traits associated
      with farming was investigated in the haploid-diploid red alga, Gracilaria
      chilensis, cultivated in Chile. This alga belongs to one of the most frequently
      cultivated seaweed genera around the world. Fifteen farmed populations, 11 wild
      populations, and two subspontaneous populations were sampled along the Chilean
      coast. The frequency of reproductive versus vegetative individuals and of haploid
      versus diploid individuals was checked in each population. In addition, the
      distribution of genetic variation in wild and cultivated populations was analyzed
      using six microsatellite markers. Our results first demonstrated that farmed
      populations are maintained almost exclusively by vegetative propagation.
      Moreover, the predominance of diploid individuals in farms showed that farming
      practices had significantly modified life-history traits as compared to wild
      populations. Second, the expected reduction in genetic diversity due to a
      cultivation bottleneck and subsequent clonal propagation was detected in farms.
      Finally, our study suggested that cultural practices in the southern part of the
      country contributed to the spread of selected genotypes at a local scale.
      Altogether, these results document for the first time that involuntary selection
      could operate during the first step of domestication in a marine plant.

PMID- 18346221
TI  - Multilocus phylogeography of a holarctic duck: colonization of north america from
      eurasia by gadwall (Anas strepera).
AB  - More than 100 species of birds have Holarctic distributions extending across
      Eurasia and North America, and many of them likely achieved these distributions
      by recently colonizing one continent from the other. Mitochondrial DNA (mtDNA)
      and five nuclear introns were sequenced to test the direction and timing of
      colonization for a Holarctic duck, the gadwall (Anas strepera). Three lines of
      evidence suggest gadwalls colonized North America from Eurasia. First, New World
      (NW) gadwalls had fewer alleles at every locus and 61% of the allelic richness
      found in Old World (OW) gadwalls. Second, NW gadwalls had lower mtDNA allelic
      richness than other NW ducks. Third, coalescent analysis suggested that less than
      5% of the ancestral population contributed to NW gadwalls at the time of
      divergence. Gadwalls likely colonized North America during the Late Pleistocene
      (approximately 81,000 years ago), but the confidence interval on that estimate
      was large (8500-450,000 years ago). Intercontinental gene flow and selection also
      likely contributed to genetic diversity in gadwalls. This study illustrates the
      use of multiple loci and coalescent analyses for critically testing a priori
      hypotheses regarding dispersal and colonization and provides an independent
      datapoint supporting an OW to NW bias in the direction of colonization.

PMID- 18346222
TI  - Reaction norm variants for male calling song in populations of Achroia grisella
      (Lepidoptera: Pyralidae): toward a resolution of the lek paradox.
AB  - Significant additive genetic variance often occurs for male advertisement traits
      in spite of the directional selection imposed by female choice, a problem
      generally known in evolutionary biology as the lek paradox. One hypothesis, which
      has limited support from recent studies, for the resolution of this paradox is
      the role of genotype x environment interaction in which no one genotype exhibits
      the superior performance in all environments--a crossover of reaction norms.
      However, these studies have not characterized the actual variation of reaction
      norms present in natural populations, and the extent to which crossover maintains
      genetic variance remains unknown. Here, we present a study of genotype x
      environment interaction for the male calling song in populations of Achroia
      grisella (Lepidoptera: Pyralidae; lesser waxmoth). We report significant variance
      among reaction norms for male calling song in two North American populations of
      A. grisella as measured along temperature, food availability, and density
      gradients, and there is a relatively high incidence of crossover of the
      temperature reaction norms. This range of reaction norm variants and their
      crossover may reflect the co-occurrence of plastic and canalized genotypes, and
      we argue that the different responses of these variants along environmental
      gradients may contribute toward the maintenance of genetic variance for male
      song.

PMID- 18346223
TI  - Allometric space and allometric disparity: a developmental perspective in the
      macroevolutionary analysis of morphological disparity.
AB  - Here, we advance novel uses of allometric spaces--multidimensional spaces
      specifically defined by allometric coefficients--with the goal of investigating
      the focal role of development in shaping the evolution of morphological
      disparity. From their examination, operational measures of allometric disparity
      can be derived, complementing standard signals of morphological disparity through
      an intuitive and process-oriented refinement of established analytical protocols
      used in disparity studies. Allometric spaces thereby become a promising context
      to reveal different patterns of evolutionary developmental changes and to assess
      their relative prevalence and importance. Such spaces offer a novel domain of
      investigation of phenotypic variation and should help in detecting large-scale
      trends, thus placing various macroevolutionary phenomena in an explicitly
      developmental context. Ammonoidea (Cephalopoda) at the Lower-Middle Jurassic
      transition were chosen as a case study to illustrate this methodological
      approach. We constructed two phenotypic spaces: a static, adult one (adult
      morphospace) and a dynamic, developmental one (allometric space). Comparative
      disparity analyses show a strikingly stable occupation in both spaces, despite
      extensive change in taxonomic composition. In contrast, disparity analyses of
      subclades reveal clearly distinct morphological and allometric disparity
      dynamics. Allometric approaches allow developmental insights into morphological
      diversification otherwise intractable from the analysis of adult morphospace
      alone.

PMID- 18346224
TI  - The Plasmodium TRAP/MIC2 family member, TRAP-Like Protein (TLP), is involved in
      tissue traversal by sporozoites.
AB  - In the apicomplexan protozoans motility and cell invasion are mediated by the
      TRAP/MIC2 family of transmembrane proteins, members of which link extracellular
      adhesion to the intracellular actomyosin motor complex. Here we characterize a
      new member of the TRAP/MIC2 family, named TRAP-Like Protein (TLP), that is highly
      conserved within the Plasmodium genus. Similar to the Plasmodium sporozoite
      protein, TRAP, and the ookinete protein, CTRP, TLP possesses an extracellular
      domain architecture that is comprised of von Willebrand factor A (vWA) and
      thrombospondin type 1 (TSP1) domains, plus a short cytoplasmic domain. Comparison
      of the vWA domain of TLP genes from multiple Plasmodium falciparum isolates
      showed relative low sequence diversity, suggesting that the protein is not under
      selective pressures of the host immune system. Analysis of transcript levels by
      quantitative reverse transcription polymerase chain reaction (RT-PCR) showed that
      TLP is predominantly expressed in salivary gland sporozoites of P. falciparum and
      P. berghei. Targeted disruption of P. berghei TLP resulted in a decreased
      capacity for cell traversal by sporozoites, and reduced infectivity of
      sporozoites in vivo, whereas in vitro sporozoite motility and hepatocyte invasion
      were unaffected. These results indicate a role of TLP in cell traversal by
      sporozoites.

PMID- 18346225
TI  - A concerted action of HNF4alpha and HNF1alpha links hepatitis B virus replication
      to hepatocyte differentiation.
AB  - Hepatitis B virus (HBV) is an important human pathogen, which targets the liver
      extremely efficient, gaining access to hepatocytes by a so far unknown receptor
      and replicating in a hepatocyte-specific fashion. Cell differentiation seems to
      determine HBV replication. We here show that the level of hepatocyte
      differentiation, as indicated by hepatocyte polarization and metabolic activity,
      is closely correlated to the transcription of the HBV RNA pregenome. Pregenome
      transcription determined the level of HBV replication in various cell lines of
      hepatocellular origin and in primary human hepatocytes. A variety of hepatocyte
      enriched nuclear factors have been described to regulate transcription of the
      pregenome, but it remained unknown which factors link HBV replication to
      hepatocyte differentiation. We determined that high expression levels of
      HNF4alpha but not its potential cofactors or other hepatocyte-enriched
      transcription factors were essential for efficient HBV replication, and link it
      to hepatocyte differentiation. HNF1alpha contributed to the control of HBV
      replication because it regulated the expression of HNF4alpha. Thus, a concerted
      action of HNF4alpha and HNF1alpha, which also determines morphological and
      functional differentiation of hepatocytes, links HBV replication to hepatocyte
      differentiation.

PMID- 18346226
TI  - Developing object concepts in infancy: an associative learning perspective.
AB  - We present a domain-general framework called constrained attentional associative
      learning to provide a developmental account for how and when infants form
      concepts for animates and inanimates that encapsulate not only their surface
      appearance but also their movement characteristics. Six simulations with the same
      general-purpose architecture implement the features of the theory to model infant
      behavior in learning about objects' motion trajectory, their causal role, their
      onset of motion, and the initial mapping between a label and a moving object.
      Behavioral experiments with infants tested novel hypotheses generated by the
      model, showing that verbal labels initially may be associated with specific
      features rather than overall shape. Implications of the framework and model are
      discussed in relation to the mechanisms of early learning, the development of the
      animate-inanimate distinction, and the nature of development in the first years
      of life.

PMID- 18346227
TI  - National Institute of Neurological Disorders and Stroke (NINDS): advances in
      understanding and treating neuropathy, 24-25 October 2006; Bethesda, Maryland.
AB  - National Institute of Neurological Disorders and Stroke sponsored a meeting to
      explore the current status of basic and clinical research in peripheral
      neurobiology and clinical neuropathy. The goal of the workshop was to identify
      areas where additional research could lead to the development of new therapeutics
      in the next 5 years. Participants discussed the current understanding of disease
      mechanisms of axonal and demyelinating neuropathies, existing techniques in
      research, disease biomarkers, and assessment of neuropathy. Painful neuropathies
      were discussed at the basic scientific and clinical levels in relation to new
      insights into etiology and treatment. The meeting concluded with a discussion on
      therapeutic development in neuropathy and the need for a unified approach to
      multicenter trials. Short-term goals of the workshop were to form a working group
      for neuropathy, the Peripheral Neuropathy Study Group, and to translate new
      scientific findings into therapies and complete clinical trials.

PMID- 18346228
TI  - Assessment of nerve excitability in toxic and metabolic neuropathies.
AB  - Measurement of nerve excitability by threshold tracking provides complementary
      information to conventional nerve conduction studies and may be used to infer the
      activity of a variety of ion channels, energy-dependent pumps, and ion exchange
      processes activated during the process of impulse conduction. This review
      highlights recent clinical excitability studies that have suggested mechanisms
      for nerve involvement in a range of metabolic and toxic neuropathies. While
      clinical nerve excitability studies are still in their infancy, and it is too
      early to know whether they have diagnostic value, there is growing evidence of
      their utility to provide novel insights into the pathophysiological mechanisms
      involved in a variety of neuropathic disturbances.

PMID- 18346229
TI  - Chemotherapy-induced neuropathy.
AB  - Neurotoxic side effects of cancer therapy are second in frequency to
      hematological toxicity. Unlike hematological side effects that can be treated
      with hematopoietic growth factors, neuropathies cannot be treated and protective
      treatment strategies have not been effective. For the neurologist, the diagnosis
      of a toxic neuropathy is primarily based on the case history, the clinical and
      electrophysiological findings, and knowledge of the pattern of neuropathy
      associated with specific agents. In most cases, toxic neuropathies are length
      dependent, sensory, or sensorimotor neuropathies often associated with pain. The
      platinum compounds are unique in producing a sensory ganglionopathy.
      Neurotoxicity is usually dependent on cumulative dose. Severity of neuropathy
      increases with duration of treatment and progression stops once drug treatment is
      completed. The platinum compounds are an exception where sensory loss may
      progress for several months after cessation of treatment ("coasting"). As more
      effective multiple drug combinations are used, patients will be treated with
      several neurotoxic drugs. Synergistic neurotoxicity has not been extensively
      investigated. Pre-existent neuropathy may influence the development of a toxic
      neuropathy. Underlying inherited or inflammatory neuropathies may predispose
      patients to developing very severe toxic neuropathies. Other factors such as
      focal radiotherapy or intrathecal administration may enhance neurotoxicity. The
      neurologist managing the cancer patient who develops neuropathy must answer a
      series of important questions as follows: (1) Are the symptoms due to peripheral
      neuropathy? (2) Is the neuropathy due to the underlying disease or the treatment?
      (3) Should treatment be modified or stopped because of the neuropathy? (4) What
      is the best supportive care in terms of pain management or physical therapy for
      each patient? Prevention of toxic neuropathies is most important. In patients
      with neuropathy, restorative approaches have not been well established.
      Symptomatic and other management are necessary to maintain and improve quality of
      life.

PMID- 18346230
TI  - Lower touch sensibility in the extremities of healthy Indians: further
      deterioration with age.
AB  - Touch sensibility testing is a cost-effective, psychophysical measure of
      peripheral nerve function and impairment. However, there is limited information
      regarding the natural variability in touch sensibility across different
      populations and different age groups. We studied 568 healthy Indian volunteers
      without any clinical evidence of peripheral nerve disease. Touch sensibility was
      evaluated bilaterally in palms, feet, and heels, using Semmes-Weinstein
      monofilaments, with target forces ranging from 0.008 to 300 g. No differences
      were observed between the right and the left limbs. The lowest target force
      detected ranged from 0.4 to 2 g in the palms and 1.4 to 15 g in the feet. These
      values showed further increase with age. Women compared with men had higher
      sensibility in the palms in most age groups. Touch sensibility thresholds
      recorded in a large group of Indians were higher than that reported in other
      populations. These findings have clinical implications for the diagnosis of early
      nerve impairment in the elderly and in disease states drawing attention to
      geographic variations in touch sensation.

PMID- 18346231
TI  - Impairment of circulating CD4+CD25+ regulatory T cells in patients with chronic
      inflammatory demyelinating polyradiculoneuropathy.
AB  - Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune
      mediated peripheral nervous system disease. CD4+CD25+ T regulatory cells (Tregs)
      have been unequivocally shown to be critical in maintaining immune tolerance and
      preventing auto-immune diseases by suppressing self-reactive T cells. Thus, we
      hypothesized that the numbers and/or the function of Tregs would be deranged
      during the progressive or relapse phases of CIDP. The number of Tregs was
      determined by flow cytometry according to their characteristic CD4+CD25(high)
      membrane phenotype. Functional characterization of Tregs was analyzed by
      suppression of proliferation and secretion of cytokines by co-cultured effector
      CD4+CD25- T cells. FOXP3 message expression level was assessed by quantitative
      real-time polymerase chain reaction. The results showed significant reduction in
      both the number and the suppressive function of Tregs in the patients with CIDP
      compared with healthy controls. Also, Tregs isolated from CIDP patients expressed
      lower levels of FoxP3 mRNA. During the progressive or the relapsing phases of
      CIDP, the number of Tregs was reduced, and the suppressive function of them
      decreased. These findings may be helpful to our understanding of the possible
      role of Tregs in the pathogenesis of CIDP.

PMID- 18346232
TI  - Correlation between clinical/neurophysiological findings and quality of life in
      Charcot-Marie-Tooth type 1A.
AB  - Quality of life (QoL), as defined by the Short Form 36, has previously been shown
      to be abnormal in patients with Charcot-Marie-Tooth disease (CMT), both for
      Physical Composite Scores (PCS) and Mental Composite Scores (MCS). We have now
      extended these observations in a multicenter evaluation of 89 patients with
      Charcot-Marie-Tooth disease type 1A, the most common form of CMT. Both the PCS
      and MCS were abnormal also in this cohort, compared with the Italian population
      at large. In particular, the ability to ambulate independently as well as toe and
      heel walk correlated well with QoL measures in our patients.

PMID- 18346233
TI  - High- and low-frequency transcutaneous electrical nerve stimulation delay sciatic
      nerve regeneration after crush lesion in the mouse.
AB  - The stimulation of peripheral nerve regeneration has been studied in different
      ways, including the use of electrical fields. The capacity of this modality to
      enhance nerve regeneration is influenced by the parameters used, including
      current type, frequency, intensity, and means of administration. Transcutaneous
      electrical nerve stimulation (TENS) is a frequently used form of administering
      electrical current to the body, but its effects on peripheral nerve regeneration
      are not known. This study assessed the influence of TENS on sciatic nerve
      regeneration, using a model of crush lesion in the mouse. Mice were stimulated 30
      min a day, 5 days a week, for 5 weeks with both high- (100 Hz) and low- (4 Hz)
      frequency TENS. Control animals had the sciatic nerve crushed but were not
      stimulated. Assessment was performed weekly by functional analysis using the
      Static Sciatic Index for the mouse and at the end of the experiment by light and
      electron microscopy. The results showed that although there were no differences
      between the groups regarding the Static Sciatic Index values, TENS led to nerves
      with morphological signs of impaired regeneration. At light microscopy level,
      TENS nerves presented more axons with dark axoplasm, signs of edema, and a less
      organized cytoarchitecture. Electronmicrographs showed fewer and thinner thick
      myelinated fibers and increased number of Schwann cell nuclei. Myelinated axon
      diameters and density and diameter of nonmyelinated fibers were not affected by
      TENS, leading to the conclusion that this regimen of electrical stimulation leads
      to a delayed regeneration after a crush lesion of the sciatic nerve in the mouse.
      All these effects were more pronounced on high-frequency TENS nerves.

PMID- 18346234
TI  - Diagnostic value of sural nerve biopsy in patients with suspected Borrelia
      neuropathy.
AB  - Peripheral neuropathy is a recognized but incompletely understood manifestation
      of borreliosis. As the pathology of this neuropathy has been described only in
      small case series, the value of nerve biopsy findings for the pathologic
      diagnosis of Borrelia-associated neuropathy is unclear. We collected and
      investigated 21 patients with peripheral neuropathy and with typical clinical and
      serologic signs of neuroborreliosis [Borrelia neuropathy (BN)]. Standard
      histology and immunohistochemistry were performed on sural nerve biopsies using
      antibodies to CD4, CD68 and membrane attack complex C5b-9, intercellular adhesion
      molecule (ICAM)-1, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL
      6. Nine patients with idiopathic vasculitic neuropathy (VN) and 14 with
      idiopathic axonal neuropathy (AN) served as disease controls. In BN, the
      characteristic histology was that of an AN with transmural or perivascular
      lymphocytic infiltration of nerve vessels. In BN, but less in VN and AN,
      perineurial thickening and neovascularization were observed. For BN but not for
      VN, this thickening correlated with increased perineurial immunoreactivity (IR)
      to TNF-alpha, C5b-9, and ICAM-1. In comparison to AN, both BN and VN displayed
      increased perineurial T-cell infiltration and human leukocyte antigen (HLA)-DR3
      IR. In the endoneurium, cytokine (IL-1beta, IL-6, TNF-alpha), HLA-DR3, and ICAM-1
      expression was more pronounced in VN but not in BN. The neuropathy in patients
      with neuroborreliosis resembles idiopathic VN but shows some distinctive
      features. None of the findings of this study are disease specific but as a
      pattern may help support the diagnosis of inflammatory neuropathy in patients
      with serological evidence for Borrelia infection.

PMID- 18346235
TI  - Measurement of forelimb function by digital video motion analysis in rat nerve
      transection models.
AB  - The object of this study was to demonstrate that digital video motion analysis is
      a quantitative, valid, and reproducible method for evaluation of function in the
      rat model of forelimb nerve transection and repair. Median, ulnar, and radial
      nerves were transected and directly repaired in 220 g Sprague-Dawley rats. Normal
      rats and sham-operated rats served as controls (six rats in each group). Two
      dimensional (2D) digital video motion analysis was used to capture the gait cycle
      and quantify joint movement and changes in toe spread. Recordings were made
      preoperatively and at 1, 4, 8, 12, and 16 weeks postoperatively. Wrist and
      metacarpophalangeal (MP) joint extension decreased after radial nerve injury, and
      wrist and MP joint flexion decreased after combined median and ulnar nerve injury
      or injury to the median nerve only. Toe spread decreased after combined median
      and ulnar nerve injury and after radial nerve injury. Median or ulnar nerve
      injury alone did not lead to a significant change in toe spread. 2D digital video
      motion analysis can be used to quantify movement of the wrist and the MP joint in
      rats. It is a valid method to evaluate functional deficit and recovery after
      nerve injury and repair in the forelimb.

PMID- 18346236
TI  - Nerve biopsy is still very useful: a personal view.

PMID- 18346237
TI  - Measles quarantine--the individual and the public.

PMID- 18346238
TI  - Attitudes toward predeployment and experimental vaccinations among troops
      deployed to Operation Iraqi Freedom and Operation Enduring Freedom.
AB  - BACKGROUND: The Department of Defense is actively engaged in the research and
      development of vaccine(s) to mitigate the burden of disease associated with
      diarrhea among deployed troops. Soldiers' attitudes and beliefs toward
      predeployment vaccines and participation in experimental research with vaccines
      are unknown. METHODS: To assess these attitudes, a survey was distributed among
      soldiers who had been and were currently deployed to Operations Iraqi and
      Enduring Freedom. RESULTS: Sixty-one percent of soldiers believe that
      predeployment vaccines are important, and 21% are hesitant to receive these
      vaccinations. Fifteen percent of soldiers stated that they would be willing to
      enroll in a study evaluating experimental vaccines, and 14% stated that they
      would participate in military research for vaccine development. Both male and
      female soldiers agreed that predeployment vaccines were important (86 and 92%,
      respectively); however, compared to their male counterparts, females were more
      hesitant to receive routine vaccinations (45% vs 37%) and less likely to
      volunteer for an experimental vaccine study (12% vs 20%). Officers and Air Force
      personnel were less hesitant to receive routine vaccinations compared to enlisted
      and other service personnel, respectively. Furthermore, if a soldier experienced
      three or more episodes of diarrhea, he or she was more likely to try an
      experimental vaccine to prevent diarrhea (23% vs 13%, p < 0.0001). CONCLUSIONS: A
      disconnect exists between the belief that immunizations are important and the
      hesitancy to receive them. Future studies should be directed to understand this
      gap and emphasize the critical importance of vaccines for health of US personnel
      in garrison and on deployment.

PMID- 18346239
TI  - Impact of vaccines given during pregnancy on the offspring of women consulting a
      travel clinic: a longitudinal study.
AB  - BACKGROUND: Little is known on the impact of travel vaccinations during pregnancy
      on child outcomes, in particular on the long-term psychomotor development. The
      objectives of the study were (1) to estimate the rate of premature births,
      congenital abnormalities, and mental and physical development problems of
      children born from mothers who had been vaccinated during pregnancy and (2) to
      compare these rates with those of children whose mothers had not been vaccinated
      during pregnancy. METHODS: Longitudinal study including (1) retrospectively
      pregnant women having attended our travel clinic before (vaccinated) and (2)
      prospectively mothers attending our clinic (nonvaccinated). We performed phone
      interviews with mothers vaccinated during pregnancy, up to 10 years before, and
      face-to-face interviews with nonvaccinated age-matched mothers, ie, women
      attending the travel clinic who had one child of about the same age as the one of
      the case to compare child development between both groups. RESULTS: Fifty-three
      women vaccinated during pregnancy were interviewed as well as 53 nonvaccinated
      ones. Twenty-eight (53%) women received their vaccination during the first
      trimester. The most frequent vaccine administered was hepatitis A (55% of the
      cases), followed by di-Te (34%), IM poliomyelitis (23%), yellow fever (12%), A-C
      meningitis (8%), IM typhoid (4%), and oral poliomyelitis (4%). Children were
      followed for a range of 1 to 10 years. Rates of premature births were 5.7% in
      both groups; congenital abnormalities were 1.9% in the vaccinated cohort versus
      5.7% in the nonvaccinated one; children took their first steps at a median age of
      12 months in both cohorts; among schoolchildren, 5% of the vaccinated cohort
      versus 7.7% of the nonvaccinated attended a lower level or a specialized school.
      CONCLUSION: In this small sample size, there was no indication that usual travel
      vaccinations, including the yellow fever one, had deleterious effect on child
      outcome and development.

PMID- 18346240
TI  - Measles exportation from Japan to the United States, 1994 to 2006.
AB  - BACKGROUND: Imported measles cases and outbreaks involving Japanese travelers
      have been reported from the United States and other countries. For the United
      States, Japan is the top country of origin. The aims of this study were to
      analyze measles exportation trends from Japan to the United States and to suggest
      recommendations for improving monitoring and control in both countries. METHODS:
      Reviewing all exportation cases reported to the Centers for Disease Control and
      Prevention and sentinel measles activity data monitored by the Japanese Ministry
      of Health between January 1994 and December 2006 (observation period). RESULTS: A
      total of 63 cases were reported (median = 4 cases per year). Cases ranged in age
      from 9 months to 53 years (median = 17 y). Peaks occurred at 13 to 26 years and
      12 to 35 months. Six cases were US citizens and 57 Japanese. Ten cases were
      reported in July and August, followed by eight in February and March. Twenty
      seven cases were reported from Hawaii, followed by 15 from California and 6 from
      New York. Seven cases developed the secondary spread. Three of the cases had
      previously received one dose of measles vaccine, compared to 35 who were never
      immunized (25 cases unknown). During the observation period, measles activity
      exceeded the warning level in 157 weeks, with measles exportation occurring the
      subsequent week for 30 of these weeks. In comparison, during the 521 weeks in
      which measles activity was below the warning level, exportation of measles the
      following week was observed for 21 of those weeks (OR = 5.62, 95% CI = 3.12-10.2,
      p < 0.001). CONCLUSIONS: Trend of exported measles cases from Japan to the United
      States has corresponded with the measles activity trend in Japan. Most of the
      cases were unvaccinated. This international health problem should be solved by
      strong leadership of Japanese public health professionals.

PMID- 18346241
TI  - Tuberculosis risk in US Peace Corps Volunteers, 1996 to 2005.
AB  - BACKGROUND: With the popularity of international travel increasing, more
      travelers in endemic areas may increase their risk of tuberculosis (TB). We
      analyzed Peace Corps data to assess the risk of TB in long-term travelers from
      the United States. METHODS: We analyzed purified protein derivative (PPD)
      conversion and acute TB case data from the Peace Corps Epidemiological
      Surveillance System as well as postservice claims data. We calculated the risk of
      PPD conversion and active TB in all countries with Peace Corps Volunteers between
      1996 and 2005 and compared these risks with other published data. RESULTS: The
      overall incidence rates for positive PPD conversions and active TB cases are
      1.283 and 0.057 per 1,000 Volunteer-months, respectively. The Africa region had
      the highest PPD conversion rate of 1.467 conversions per 1,000 Volunteer-months
      as well as the highest active TB rate of 0.089 cases per 1,000 Volunteer-months.
      Per-country incidence rates for PPD conversions and active TB cases ranged widely
      from 0.000 to 5.514 cases and 0.000 to 2.126 cases per 1,000 Volunteer-months,
      respectively. In countries identified as "high risk," there were 1.436 cases of
      PPD conversions and 0.084 cases of active TB per 1,000 Volunteer-months.
      CONCLUSIONS: Peace Corps Volunteers have significantly higher rates of TB when
      compared to the average US population but much lower than those reported for
      travelers to highly endemic countries. Volunteers assigned to highly endemic
      countries still have a lower risk compared to other travelers to those same
      countries. Keeping in mind that Peace Corps Volunteers are a unique population,
      these data may be useful in providing medical advice to long-term travelers.

PMID- 18346242
TI  - Fatalities in the Peace Corps: a retrospective study, 1984 to 2003.
AB  - BACKGROUND: To determine causes of death for Peace Corps Volunteers (PCV) between
      1984 and 2003 and compare them with prior Volunteer death rates and with US death
      rates. METHODS: We conducted a retrospective cohort study of all PCV between 1984
      and 2003 and compared them to published data for prior years and against US death
      rates. RESULTS: Of the 66 deaths in our study period, the major causes were
      unintentional injury, homicide, medical illness, and suicide. Comparisons to US
      mortality data controlled for age, marital status, and educational attainment
      found equal or lower death rates among Volunteers. When compared to previous
      study results from 1961 to 1983, the total number of deaths, as well as the death
      rate per Volunteer-year, decreased. Deaths from unintentional injury, suicide,
      and medical illness decreased in number and rate; only homicides increased in
      number during our study period, but this increase did not reach statistical
      significance. CONCLUSIONS: PCV are exposed to unique risks, but these risks have
      become significantly less fatal over the past 20 years when compared to prior
      Peace Corps data and matched US population data.

PMID- 18346243
TI  - The evaluation, management, and prevention of stingray injuries in travelers.

PMID- 18346244
TI  - Economic aspects of travelers' diarrhea.

PMID- 18346245
TI  - Atypical Plasmodium vivax malaria in a traveler: bilateral hydronephrosis, severe
      thrombocytopenia, and hypotension.
AB  - We report a case of Plasmodium vivax infection manifested as severe
      thrombocytopenia, bilateral hydronephrosis, and hypotension in a returning
      traveler from a malaria-endemic area in Venezuela. While most of the efforts to
      prevent malaria in travelers focus on the life-threatening consequences of
      Plasmodium falciparum malaria, nonimmune travelers who encounter infection with P
      vivax may also develop serious complications. This case highlights the importance
      of preventing malaria cases among nonimmune or semi-immune individuals traveling
      to P vivax-endemic areas.

PMID- 18346246
TI  - Fatal Israeli spotted fever in a UK traveler to South Portugal.
AB  - A 63-year-old previously healthy woman developed a severe systemic infection 5
      days after returning from a holiday to Southern Portugal. She subsequently died,
      and polymerase chain reaction of a blood sample was positive for Rickettsia
      conorii ssp israeliensis. The prevalence of severe forms of this illness in the
      Mediterranean Basin is discussed.

PMID- 18346247
TI  - Measles in travelers: are we aware enough?
AB  - Measles is still an important public health concern in most developing countries.
      Nonimmune or single-dose vaccinees traveling to high-endemic countries should be
      advised on the risk of acquiring the infection. We describe two cases of imported
      measles in Spanish travelers.

PMID- 18346248
TI  - Q Fever in returned febrile travelers.
AB  - Despite the worldwide distribution of Coxiella burnetii, Q fever is not a
      frequent infection in travelers. This disease should be considered in recent
      travelers from the tropics with unknown fever, headache, raised liver enzymes,
      and low platelets. Five cases in western travelers to the tropics returning with
      fever are presented.

PMID- 18346249
TI  - Severe facial edema at high altitude.
AB  - We present a complication associated with high altitude of unusual severity.
      Pronounced facial edema developed in a 27-year-old woman during a trek to
      Kilimanjaro, Tanzania. The development of facial edema has previously been
      documented in visitors unaccustomed to high altitude. The possible
      pathophysiological mechanisms are discussed, and the importance of adhering to
      recommended ascent rates is emphasized for all high-altitude treks.

PMID- 18346250
TI  - Bat-associated histoplasmosis can be transmitted at entrances of bat caves and
      not only inside the caves.
AB  - Our observation of histoplasmosis cases augments the current knowledge on
      transmission by bats. In the presented cases, the only contact happened in the
      proximity of a bat cave but not inside the cave. We wish to communicate and
      stress that even outside of caves, bats may disperse the organism.

PMID- 18346251
TI  - Panton-Valentine leukocidin-producing methicillin-Sensitive Staphylococcus aureus
      as a cause for recurrent, contagious skin infections in young, healthy travelers
      returned from a tropical country: a new worldwide public health problem?
AB  - Skin infections associated with visits to tropical countries are well known. In
      most of the cases, the infection is caused by Staphylococcus aureus. After a
      sufficient antibiotic treatment, the skin infections resolve without any
      sequelae. But several patients suffer from recurrent skin infections. Panton
      Valentine leukocidin (PVL) is a cytotoxin produced by S aureus, which is
      associated with severe necrotic skin lesions and with a high contagiosity.

PMID- 18346253
TI  - Spontaneous splenic rupture due to Plasmodium vivax in a traveler.

PMID- 18346255
TI  - Epidemiological survey of Vibrio vulnificus infection in Japan between 1999 and
      2003.
AB  - The frequency of Vibrio vulnificus infection is very rare and there are many
      questions regarding its epidemiology in Japan. To investigate the clinical course
      and epidemiology of V. vulnificus infection in Japan, we performed a
      retrospective questionnaire survey in which 1693 hospitals from all over Japan
      were surveyed, including advanced life saving emergency centers and dermatology
      institutions. Of the 1693 hospitals, we received answers from 1045. Ninety-four
      cases were confirmed as V. vulnificus infections during 1999 and 2003. Sixty
      eight (72.3%) of the 94 patients had the septic type infection with a mortality
      rate of 75.0% (51/68 patients died). The prognosis of patients with the septic
      type was worse than that of the wound type (P < 0.001). V. vulnificus infections
      occurred from June to November and none occurred in winter. Many infections
      occurred in western Japan with the majority of infections (50/94) occurring in
      Kyushu. In particular, 43 infections occurred in marine coastal areas of the
      Ariake and Yatsushiro Seas, which have many tidelands. Seventy-seven of 89
      patients (86.5%) had liver function impairment as an underlying disease, and 53
      (59.6%) had liver cirrhosis, of whom nine (10.1%) suffered from liver cancer. The
      incidence of V. vulnificus infection was different according to districts.
      Geographic and climatic factors also contributed to the occurrence of V.
      vulnificus infection.

PMID- 18346256
TI  - Pattern of skin and nail changes in chronic renal failure in Nepal: a hospital
      based study.
AB  - Chronic renal failure, regardless of its cause, often produces specific
      dermatological abnormalities, which can develop long before failure manifests
      clinically. Our aim was to study the clinical pattern of skin and nail changes in
      chronic renal failure and also study the associations of these changes with age,
      sex, etiology and duration of the chronic renal failure. A total of 104 diagnosed
      cases of chronic renal failure were included in the study over a period of 1
      year. Equal numbers of age- and sex-matched individuals were taken as controls.
      The male : female ratio was 1.4:1. The mean duration of chronic renal failure was
      19 +/- 20 months. Among cases and controls, 72% and 16% had skin changes,
      respectively. Xerosis was the most common of the skin changes (28%), followed by
      hyperpigmentation (20%), pruritus (15%), infectious diseases (5%) and other skin
      changes (33%) in chronic renal failure patients. Abnormal nail changes were seen
      in 82% of the cases compared to only 8% of the controls. In the cases, white nail
      was most common followed by brown and half-and-half nail. Pruritus was
      significantly higher in the dialysis group whereas the nail changes were
      significantly higher in the non-dialysis group. The skin and nail changes were
      common in chronic renal failure and manifested in various forms. Thus, thorough
      inspection of the integument might reveal markers of occult renal disease.

PMID- 18346257
TI  - Preliminary study among truck drivers in Turkey: effects of ultraviolet light on
      some skin entities.
AB  - In this study, we aimed to compare driver (left) and opposite (right) sides for
      some skin entities in drivers. We also evaluated the effect of occupational
      duration, age and skin type among this population. One hundred and forty-eight
      truck drivers were included in this study. Sun exposed areas were classified.
      Dermatological entities such as actinic keratosis, solar lentigo, seborrheic
      keratosis, melanocytic nevus, spider angioma, ephelid, basal cell carcinoma
      (BCC), squamous cell carcinoma, and melanoma were compared to driver and right
      sides. In addition, drivers were divided into two subgroups according to: (i) age
      (subgroups A1, 20-40 years, and A2, >40 years); (ii) occupational duration
      (subgroups O1, 1-10 years, and 02, >10 years); and (iii) skin type (subgroups S1,
      skin types I and II, and S2, skin types III and IV. Each of the two subgroups
      were compared with respect to the total prevalence (left and right sides) of
      lesions excluding the location. Seborrheic keratosis and lentigo solaris were
      found to be increased on the driver side of the face (P = 0.00) and ear (P =
      0.013), respectively. Statistically significant increases of lesions on the
      driver side were determined according to the subgroups: melanocytic nevi were
      found to be increased on the driver side in A1 (P = 0.00), A2 (P = 0.00), O2 (P =
      0.00), S1 (P = 0.00) and S2 (P = 0.006) groups; actinic keratoses were found to
      be significantly increased on the driver side in A2 and O2 groups (P = 0.03 for
      both).

PMID- 18346258
TI  - Discoid lupus erythematosus exacerbated by contact dermatitis caused by use of
      squaric acid dibutylester for topical immunotherapy in a patient with alopecia
      areata.
AB  - A 57-year-old Japanese male patient with an 18-year history of discoid lupus
      erythematosus (DLE) presented with alopecia on his scalp, and was clinically
      diagnosed to have alopecia areata. He was started on topical immunotherapy with
      squaric acid dibutylester (SADBE) for the treatment of alopecia areata. The
      patient was first sensitized with the application of 2% SADBE on the right upper
      arm, followed subsequently by re-exposure to a low concentration of SADBE to
      provoke contact dermatitis on the scalp as treatment. Approximately 2 months
      later, he developed multiple red scaly lesions on his scalp and face, which were
      diagnosed histopathologically as DLE. DLE is known to be exacerbated by a variety
      of factors, including sunlight, X-rays, tattoos, burns, and some forms of
      cutaneous trauma, including dermatitis. However, to the best of our knowledge,
      there have only been two reported cases of DLE exacerbated by contact dermatitis.

PMID- 18346259
TI  - Multiple cutaneous neoplasms in a patient with Rothmund-Thomson syndrome: case
      report and published work review.
AB  - Rothmund-Thomson syndrome (RTS) is a rare genodermatosis characterized by early
      poikilodermatous skin lesions, often combined with juvenile cataracts,
      photosensitivity and bone defects. Data in the published work indicate that there
      is an increased risk of RTS patients developing malignant tumors. Herein, we
      report the multiple skin carcinomas observed in a case of RTS and review the
      published work on the occurrence of malignant tumors in these patients. We report
      the case of a 63-year-old male with RTS who developed multiple cutaneous
      neoplasms (three basal cell carcinomas, three squamous cell carcinomas and
      Bowen's disease) over the previous 15 years. A published work review confirmed
      that RTS is a genetic condition that predisposes subjects to the development of
      bone tumors, especially at an early age, and skin tumors at an adult age.
      Therefore, alongside careful osteoarticular monitoring to identify a bone tumor
      quickly, during the life of a patient suffering from the syndrome, it is just as
      important to take appropriate preventive action and monitor the possible onset of
      skin tumors.

PMID- 18346260
TI  - Case of skin injuries due to stings by crown-of-thorns starfish (Acanthaster
      planci).
AB  - A case of skin injuries due to stings by crown-of-thorns starfish, Acanthaster
      planci, in a 53-year-old Okinawan woman is reported. She went to a beach to
      gather shellfish on 8 April 2001 and fell to the ground with her left palm on a
      crown-of-thorns starfish that happened to be close to her. She hurried to the
      emergency section of our hospital. An emergency doctor sterilized the wound and
      administered an antibiotic, an analgesic agent and an injection of a tetanus
      antitoxin. He tried to remove the remaining spines from the palm with great
      difficulty. Because swelling and subcutaneous indurations of the left palm had
      persisted thereafter, oral and topical administration of corticosteroid started
      on 13 April. Physical examination at the dermatology section revealed
      approximately 10 stab wounds of the left palm with pus, subcutaneous bleeding and
      many abrasions around them. X-rays of the left hand showed foreign bodies, 2-10
      mm in size, located on the lesions. The patient was treated with a topical
      injection of 2 mg triamcinolone acetonide (Kenacort-A), diluted fivefold with 1%
      Xylocaine, once a week. Some of the foreign body granulomatous lesions improved
      but pain and subcutaneous indurations persisted in most of the lesions. Because
      the X-ray photographs showed many remaining spines, surgical excision to remove
      them was performed under local anesthesia 3 months after the injury. All the
      symptoms improved after the operation. Scanning electron microscopic examination
      of the spines revealed that their tips had fragile lattice-like structures.

PMID- 18346261
TI  - Treatment trial of multicentric reticulohistiocytosis with a combination of
      predonisolone, methotrexate and alendronate.

PMID- 18346262
TI  - Keratosis lichenoides chronica treated with acitretin plus narrowband ultraviolet
      B phototherapy.

PMID- 18346263
TI  - Acute cutaneous toxicity of methotrexate representing a Koebner-like phenomenon.

PMID- 18346264
TI  - Two cases of phaeohyphomycosis due to Exophiala jeanselmei.

PMID- 18346265
TI  - Case of anaphylaxis due to fish and shellfish.

PMID- 18346266
TI  - Hemorrhagic bullae as cutaneous metastasis from primary uterine leiomyosarcoma.

PMID- 18346267
TI  - Metastatic gastric carcinoma presenting as an erythema annulare centrifugum-like
      lesion.

PMID- 18346269
TI  - Hypermethylated MAL gene - a silent marker of early colon tumorigenesis.
AB  - BACKGROUND: Tumor-derived aberrantly methylated DNA might serve as diagnostic
      biomarkers for cancer, but so far, few such markers have been identified. The aim
      of the present study was to investigate the potential of the MAL (T-cell
      differentiation protein) gene as an early epigenetic diagnostic marker for
      colorectal tumors. METHODS: Using methylation-specific polymerase chain reaction
      (MSP) the promoter methylation status of MAL was analyzed in 218 samples,
      including normal mucosa (n = 44), colorectal adenomas (n = 63), carcinomas (n =
      65), and various cancer cell lines (n = 46). Direct bisulphite sequencing was
      performed to confirm the MSP results. MAL gene expression was investigated with
      real time quantitative analyses before and after epigenetic drug treatment.
      Immunohistochemical analysis of MAL was done using normal colon mucosa samples (n
      = 5) and a tissue microarray with 292 colorectal tumors. RESULTS: Bisulphite
      sequencing revealed that the methylation was unequally distributed within the MAL
      promoter and by MSP analysis a region close to the transcription start point was
      shown to be hypermethylated in the majority of colorectal carcinomas (49/61, 80%)
      as well as in adenomas (45/63, 71%). In contrast, only a minority of the normal
      mucosa samples displayed hypermethylation (1/23, 4%). The hypermethylation of MAL
      was significantly associated with reduced or lost gene expression in in vitro
      models. Furthermore, removal of the methylation re-induced gene expression in
      colon cancer cell lines. Finally, MAL protein was expressed in epithelial cells
      of normal colon mucosa, but not in the malignant cells of the same type.
      CONCLUSION: Promoter hypermethylation of MAL was present in the vast majority of
      benign and malignant colorectal tumors, and only rarely in normal mucosa, which
      makes it suitable as a diagnostic marker for early colorectal tumorigenesis.

PMID- 18346270
TI  - Axonin-1/TAG-1 is required for pathfinding of granule cell axons in the
      developing cerebellum.
AB  - BACKGROUND: Neural development consists of a series of steps, including
      neurogenesis, patterning, cell migration, axon guidance, and finally,
      synaptogenesis. Because all these steps proceed in a constantly changing
      environment, functional gene analyses during development have to take time into
      account. This is quite challenging, however, as loss-of-function approaches based
      on classic genetic tools do not allow for the precise temporal control that is
      required for developmental studies. Gene silencing by RNA interference (RNAi) in
      combination with the chicken embryo or with cultured embryos opens new
      possibilities for functional gene analysis in vivo. Axonin-1/TAG-1 is a cell
      adhesion molecule of the immunoglobulin superfamily with a well defined temporal
      and spatial expression pattern in the developing vertebrate nervous system.
      Axonin-1/TAG-1 was shown to promote neurite outgrowth in vitro and to be required
      for commissural and sensory axon pathfinding in vivo. RESULTS: To knock down
      axonin-1 in a temporally and spatially controlled manner during development of
      the nervous system, we have combined RNAi with the accessibility of the chicken
      embryo even at late stages of development. Using ex ovo RNAi, we analyzed the
      function of axonin-1/TAG-1 in cerebellar development. Axonin-1 is expressed in
      postmitotic granule cells while they extend their processes, the parallel fibers.
      In the absence of axonin-1 these processes still extend but no longer in a
      parallel manner to each other or to the pial surface of the cerebellum.
      CONCLUSION: Axonin-1/TAG-1 is required for the navigation, but not for the
      elongation, of granule cell processes in the developing cerebellum in vivo.

PMID- 18346271
TI  - Primary multifocal osseous Hodgkin's lymphoma.
AB  - BACKGROUND: Hodgkin's disease (HD) most commonly presents with progressive
      painless enlargement of peripheral lymph nodes, especially around the cervical
      region. A few children have systemic symptoms and weight loss. At the time of
      diagnosis, osseous involvement is uncommon CASE PRESENTATION: A case is described
      of Primary Multifocal Osseous Hodgkin's Lymphoma in a seven-year-old boy. He
      presented with a painful swelling in the sternum, and further investigations
      revealed deposits in his L1 vertebra, the left sacro-iliac joint and the right
      acetabulum. CONCLUSION: The clinical, radiological and histological features of
      this disease can mimic other medical conditions, including Tuberculosis, making
      the diagnosis difficult and often leading to delays in treatment. This is a very
      rare condition and we believe this to be the youngest reported case in the
      literature.

PMID- 18346272
TI  - Proteomic analysis of the EhV-86 virion.
AB  - BACKGROUND: Emiliania huxleyi virus 86 (EhV-86) is the type species of the genus
      Coccolithovirus within the family Phycodnaviridae. The fully sequenced 407,339 bp
      genome is predicted to encode 473 protein coding sequences (CDSs) and is the
      largest Phycodnaviridae sequenced to date. The majority of EhV-86 CDSs exhibit no
      similarity to proteins in the public databases. RESULTS: Proteomic analysis by 1
      DE and then LC-MS/MS determined that the virion of EhV-86 is composed of at least
      28 proteins, 23 of which are predicted to be membrane proteins. Besides the major
      capsid protein, putative function can be assigned to 4 other components of the
      virion: two lectin proteins, a thioredoxin and a serine/threonine protein kinase.
      CONCLUSION: This study represents the first steps toward the identification of
      the protein components that make up the EhV-86 virion. Aside from the major
      capsid protein, whose function in the virion is well known and defined, the
      nature of the other proteins suggest roles involved with viral budding, caspase
      activation, signalling, anti-oxidation, virus adsorption and host range
      determination.

PMID- 18346273
TI  - Systemic TNF blockade does not modulate synovial expression of the pro
      inflammatory mediator HMGB1 in rheumatoid arthritis patients--a prospective
      clinical study.
AB  - INTRODUCTION: High-mobility group box chromosomal protein 1 (HMGB1) has recently
      been identified as an endogenous mediator of arthritis. TNF and IL-1beta, pivotal
      cytokines in arthritis pathogenesis, both have the ability to induce the release
      of HMGB1 from myeloid and dendritic cells. It was, therefore, decided to
      investigate whether treatment based on TNF blockade in rheumatoid arthritis (RA)
      affects the expression of synovial HMGB1. METHODS: Repeated arthroscopy-guided
      sampling of synovial tissue was performed in nine patients with RA before and
      nine weeks after initiation of anti-TNF mAb (infliximab) therapy. Synovial biopsy
      specimens were analysed for HMGB1 protein by immunohistochemical staining and for
      HMGB1 mRNA expression by real-time reverse transcriptase PCR (RT-PCR).
      Statistical evaluations were based on Wilcoxon's signed rank tests or Spearman
      rank sum tests. RESULTS: Aberrant, extranuclear HMGB1 and constitutive nuclear
      HMGB1 expression, with histological signs of inflammation, were evident in all
      biopsies obtained before infliximab therapy. Signs of inflammation were still
      evident in the second biopsies obtained nine weeks after initiation of infliximab
      therapy. The cytoplasmic and extracellular expression of HMGB1 decreased in five
      patients, remained unchanged in one patient and increased in three patients,
      making the overall change in HMGB1 protein expression not significant. No
      correlation between the clinical response, as measured by disease activity score
      calculated for 28 joints (DAS28) or the American College of Rheumatology response
      criteria (ACR 20, 50, and 70), and the direction of change of HMGB1 expression in
      individual patients could be discerned. In addition, infliximab therapy did not
      alter HMGB1 mRNA synthesis. CONCLUSION: Pro-inflammatory HMGB1 expression during
      rheumatoid synovitis was not consistently influenced by TNF-blocking therapy with
      infliximab. This suggests that TNF is not the main inducer of extranuclear HMGB1
      during synovitis and that HMGB1 may represent a TNF-independent molecule that
      could be considered as a possible target for future therapeutic intervention in
      RA.

PMID- 18346274
TI  - Does productivity influence priority setting? A case study from the field of CVD
      prevention.
AB  - In this case study, different measures aimed at preventing cardiovascular
      diseases (CVD) in different target groups have been ranked based on cost per QALY
      from a health care sector perspective and from a societal perspective,
      respectively. The innovation in this study is to introduce a budget constraint
      and thereby show exactly which groups would be included or excluded in treatment
      or intervention programs based on the two perspectives. Approximately 90% of the
      groups are included in both perspectives. Mainly elderly women are excluded when
      the societal perspective is used and mainly middle-aged men are excluded when the
      health care sector perspective is used. Elderly women have a higher risk of CVD
      and generally lower income than middle-aged men. Thus the exclusion of older
      women in the societal perspective is not a trivial consequence since it is in
      conflict with the general interpretation of the "treatment according to need"
      rule, as well as societal goals regarding gender equality and fairness. On the
      other hand, the exclusion of working individuals in the health care perspective
      undermines a growth of public resources for future health care for the elderly.
      The extent and consequences of this conflict are unclear and empirical studies of
      this problem are rare.

PMID- 18346275
TI  - Potential factors affecting semen quality in the Asian elephant (Elephas
      maximus).
AB  - BACKGROUND: One of the major obstacles in using artificial insemination to manage
      genetics of elephant population in captivity is the large variations in semen
      quality among ejaculates within the same and among individuals. The objectives of
      this study were to determine the influences of (1) age (2) seasonality (3) and
      circulating testosterone (SrTest), triiodothyronine (SrT3) and tetraiodothyronine
      (SrT4), as well as seminal (4) testosterone (SpTest), zinc (SpZn) and protein
      (SpTP) on semen quality in the Asian elephant METHODS: Analyses, including
      motility, viability and morphology were performed in semen samples collected
      twice monthly from 13 elephant bulls (age range, 10-to 72-years) by manual
      stimulation between July 2004 and June 2005. Serum samples obtained monthly were
      assessed for SrTest, SrT3, SrT4, and seminal plasma samples were evaluated for,
      SpTest, SpZn and SpTP. RESULTS: The highest semen quality was observed at age 23
      to 43 years. Percentages of progressive motility and viable sperm were lowest at
      age 51 to 70 years (P < 0.05); on the other hand, sperm concentration was lowest
      at age 10 to 19 years (P < 0.05). Percentage of sperm with normal morphology was
      highest at age 23 to 43 years. The levels of SrT3, SrTest, SpTest and SpZn were
      lowest at age 51 to 70 years, whereas SrT4 was lowest at age 23 to 43 years.
      Seasonality significantly affected semen characteristics in which percentage of
      viable sperm and cell concentration were highest during rainy season and lowest
      during summer months (P < 0.05). However, percentage of sperm with normal
      morphology was highest in summer and lowest in rainy season (P < 0.05).
      Seasonality significantly influenced SrTest with elevated concentrations observed
      in rainy season and winter (P < 0.05). CONCLUSION: This study indicates that age
      and seasonality had influence on semen characteristics in the Asian elephant. The
      knowledge obtained in this study will improve our understanding of the
      reproductive biology of this species.

PMID- 18346276
TI  - Penicillium species as a rare isolate in tracheal granulation tissue: a case
      series.
AB  - INTRODUCTION: Granulation tissue formation is a major problem complicating the
      treatment of upper airway stenosis. We present two cases of recurrent tracheal
      granulation tissue colonisation by Penicillium species in patients undergoing
      laryngotracheal reconstructive surgery for post-intubation tracheal stenosis. We
      believe that although most Penicillium species do not cause invasive disease they
      can be a contributory factor to the occurrence of upper airway stenosis. CASE
      PRESENTATION: A microbiological and mycological study of tracheal granulation
      tissue in two patients with recurrent laryngotracheal stenosis was carried out.
      Penicillium species was seen microscopically and cultured from tracheal
      granulation tissue. Neither patient grew any bacteria known to be associated with
      airway granulation tissue formation. Amphotericin B, itraconazole, flucytosine
      voriconazole and caspofungin were highly active against both isolates.
      CONCLUSION: A search for a fungal cause should form part of the investigation for
      recurrent tracheal granulation tissue during laryngotracheal reconstruction.

PMID- 18346277
TI  - Altering the coenzyme preference of xylose reductase to favor utilization of NADH
      enhances ethanol yield from xylose in a metabolically engineered strain of
      Saccharomyces cerevisiae.
AB  - BACKGROUND: Metabolic engineering of Saccharomyces cerevisiae for xylose
      fermentation into fuel ethanol has oftentimes relied on insertion of a
      heterologous pathway that consists of xylose reductase (XR) and xylitol
      dehydrogenase (XDH) and brings about isomerization of xylose into xylulose via
      xylitol. Incomplete recycling of redox cosubstrates in the catalytic steps of the
      NADPH-preferring XR and the NAD+-dependent XDH results in formation of xylitol by
      product and hence in lowering of the overall yield of ethanol on xylose.
      Structure-guided site-directed mutagenesis was previously employed to change the
      coenzyme preference of Candida tenuis XR about 170-fold from NADPH in the wild
      type to NADH in a Lys274-->Arg Asn276-->Asp double mutant which in spite of the
      structural modifications introduced had retained the original catalytic
      efficiency for reduction of xylose by NADH. This work was carried out to assess
      physiological consequences in xylose-fermenting S. cerevisiae resulting from a
      well defined alteration of XR cosubstrate specificity. RESULTS: An isogenic pair
      of yeast strains was derived from S. cerevisiae Cen.PK 113-7D through chromosomal
      integration of a three-gene cassette that carried a single copy for C. tenuis XR
      in wild-type or double mutant form, XDH from Galactocandida mastotermitis, and
      the endogenous xylulose kinase (XK). Overexpression of each gene was under
      control of the constitutive TDH3 promoter. Measurement of intracellular levels of
      XR, XDH, and XK activities confirmed the expected phenotypes. The strain
      harboring the XR double mutant showed 42% enhanced ethanol yield (0.34 g/g)
      compared to the reference strain harboring wild-type XR during anaerobic
      bioreactor conversions of xylose (20 g/L). Likewise, the yields of xylitol (0.19
      g/g) and glycerol (0.02 g/g) were decreased 52% and 57% respectively in the XR
      mutant strain. The xylose uptake rate per gram of cell dry weight was identical
      (0.07 +/- 0.02 h-1) in both strains. CONCLUSION: Integration of enzyme and strain
      engineering to enhance utilization of NADH in the XR-catalyzed conversion of
      xylose results in notably improved fermentation capabilities of recombinant S.
      cerevisiae.

PMID- 18346278
TI  - Homoplasy in genome-wide analysis of rare amino acid replacements: the molecular
      evolutionary basis for Vavilov's law of homologous series.
AB  - BACKGROUND: Rare genomic changes (RGCs) that are thought to comprise derived
      shared characters of individual clades are becoming an increasingly important
      class of markers in genome-wide phylogenetic studies. Recently, we proposed a new
      type of RGCs designated RGC_CAMs (after Conserved Amino acids-Multiple
      substitutions) that were inferred using genome-wide identification of amino acid
      replacements that were: i) located in unambiguously aligned regions of
      orthologous genes, ii) shared by two or more taxa in positions that contain a
      different, conserved amino acid in a much broader range of taxa, and iii) require
      two or three nucleotide substitutions. When applied to animal phylogeny, the
      RGC_CAM approach supported the coelomate clade that unites deuterostomes with
      arthropods as opposed to the ecdysozoan (molting animals) clade. However, a non
      negligible level of homoplasy was detected. RESULTS: We provide a direct estimate
      of the level of homoplasy caused by parallel changes and reversals among the
      RGC_CAMs using 462 alignments of orthologous genes from 19 eukaryotic species. It
      is shown that the impact of parallel changes and reversals on the results of
      phylogenetic inference using RGC_CAMs cannot explain the observed support for the
      Coelomata clade. In contrast, the evidence in support of the Ecdysozoa clade, in
      large part, can be attributed to parallel changes. It is demonstrated that
      parallel changes are significantly more common in internal branches of different
      subtrees that are separated from the respective common ancestor by relatively
      short times than in terminal branches separated by longer time intervals. A
      similar but much weaker trend was detected for reversals. The observed
      evolutionary trend of parallel changes is explained in terms of the covarion
      model of molecular evolution. As the overlap between the covarion sets in
      orthologous genes from different lineages decreases with time after divergence,
      the likelihood of parallel changes decreases as well. CONCLUSION: The level of
      homoplasy observed here appears to be low enough to justify the utility of
      RGC_CAMs and other types of RGCs for resolution of hard problems in phylogeny.
      Parallel changes, one of the major classes of events leading to homoplasy, occur
      much more often in relatively recently diverged lineages than in those separated
      from their last common ancestor by longer time intervals of time. This pattern
      seems to provide the molecular-evolutionary underpinning of Vavilov's law of
      homologous series and is readily interpreted within the framework of the covarion
      model of molecular evolution.

PMID- 18346279
TI  - Real-time PCR/MCA assay using fluorescence resonance energy transfer for the
      genotyping of resistance related DHPS-540 mutations in Plasmodium falciparum.
AB  - BACKGROUND: Sulphadoxine-pyrimethamine has been abandoned as first- or second
      line treatment by most African malaria endemic countries in favour of artemisinin
      based combination treatments, but the drug is still used as intermittent
      preventive treatment during pregnancy. However, resistance to sulphadoxine
      pyrimethamine has been increasing in the past few years and, although the link
      between molecular markers and treatment failure has not been firmly established,
      at least for pregnant women, it is important to monitor such markers. METHODS:
      This paper reports a novel sensitive, semi-quantitative and specific real-time
      PCR and melting curve analysis (MCA) assay using fluorescence resonance energy
      transfer (FRET) for the detection of DHPS-540, an important predictor for SP
      resistance. FRET/MCA was evaluated using 78 clinical samples from malaria
      patients and compared to PCR-RFLP. RESULTS: Sixty-two samples were in perfect
      agreement between both assays. One sample showed a small wild type signal with
      FRET/MCA that indicates a polyclonal infection. Four samples were not able to
      generate enough material in both assays to distinguish mutant from wild-type
      infection, six samples gave no signal in PCR-RFLP and five samples gave no
      amplification in FRET/MCA. CONCLUSION: FRET/MCA is an effective tool for the
      identification of SNPs in drug studies and epidemiological surveys on resistance
      markers in general and DHPS-540 mutation in particular.

PMID- 18346280
TI  - MutL homologs in restriction-modification systems and the origin of eukaryotic
      MORC ATPases.
AB  - The provenance and biochemical roles of eukaryotic MORC proteins have remained
      poorly understood since the discovery of their prototype MORC1, which is required
      for meiotic nuclear division in animals. The MORC family contains a combination
      of a gyrase, histidine kinase, and MutL (GHKL) and S5 domains that together
      constitute a catalytically active ATPase module. We identify the prokaryotic
      MORCs and establish that the MORC family belongs to a larger radiation of several
      families of GHKL proteins (paraMORCs) in prokaryotes. Using contextual
      information from conserved gene neighborhoods we show that these proteins
      primarily function in restriction-modification systems, in conjunction with
      diverse superfamily II DNA helicases and endonucleases. The common ancestor of
      these GHKL proteins, MutL and topoisomerase ATPase modules appears to have
      catalyzed structural reorganization of protein complexes and concomitant DNA
      superstructure manipulations along with fused or standalone nuclease domains.
      Furthermore, contextual associations of the prokaryotic MORCs and their relatives
      suggest that their eukaryotic counterparts are likely to carry out chromatin
      remodeling by DNA superstructure manipulation in response to epigenetic signals
      such as histone and DNA methylation.

PMID- 18346281
TI  - Functional mapping imprinted quantitative trait loci underlying developmental
      characteristics.
AB  - BACKGROUND: Genomic imprinting, a phenomenon referring to nonequivalent
      expression of alleles depending on their parental origins, has been widely
      observed in nature. It has been shown recently that the epigenetic modification
      of an imprinted gene can be detected through a genetic mapping approach. Such an
      approach is developed based on traditional quantitative trait loci (QTL) mapping
      focusing on single trait analysis. Recent studies have shown that most imprinted
      genes in mammals play an important role in controlling embryonic growth and post
      natal development. For a developmental character such as growth, current approach
      is less efficient in dissecting the dynamic genetic effect of imprinted genes
      during individual ontology. RESULTS: Functional mapping has been emerging as a
      powerful framework for mapping quantitative trait loci underlying complex traits
      showing developmental characteristics. To understand the genetic architecture of
      dynamic imprinted traits, we propose a mapping strategy by integrating the
      functional mapping approach with genomic imprinting. We demonstrate the approach
      through mapping imprinted QTL controlling growth trajectories in an inbred F2
      population. The statistical behavior of the approach is shown through simulation
      studies, in which the parameters can be estimated with reasonable precision under
      different simulation scenarios. The utility of the approach is illustrated
      through real data analysis in an F2 family derived from LG/J and SM/J mouse
      stains. Three maternally imprinted QTLs are identified as regulating the growth
      trajectory of mouse body weight. CONCLUSION: The functional iQTL mapping approach
      developed here provides a quantitative and testable framework for assessing the
      interplay between imprinted genes and a developmental process, and will have
      important implications for elucidating the genetic architecture of imprinted
      traits.

PMID- 18346282
TI  - Does parenting affect children's eating and weight status?
AB  - BACKGROUND: Worldwide, the prevalence of obesity among children has increased
      dramatically. Although the etiology of childhood obesity is multifactorial, to
      date, most preventive interventions have focused on school-aged children in
      school settings and have met with limited success. In this review, we focus on
      another set of influences that impact the development of children's eating and
      weight status: parenting and feeding styles and practices. Our review has two
      aims: (1) to assess the extent to which current evidence supports the hypothesis
      that parenting, via its effects on children's eating, is causally implicated in
      childhood obesity; and (2) to identify a set of promising strategies that target
      aspects of parenting, which can be further evaluated as possible components in
      childhood obesity prevention. METHODS: A literature review was conducted between
      October 2006 and January 2007. Studies published before January 2007 that
      assessed the association between some combination of parenting, child eating and
      child weight variables were included. RESULTS: A total of 66 articles met the
      inclusion criteria. The preponderance of these studies focused on the association
      between parenting and child eating. Although there was substantial experimental
      evidence for the influence of parenting practices, such as pressure, restriction,
      modeling and availability, on child eating, the majority of the evidence for the
      association between parenting and child weight, or the mediation of this
      association by child eating, was cross-sectional. CONCLUSION: To date, there is
      substantial causal evidence that parenting affects child eating and there is much
      correlational evidence that child eating and weight influence parenting. There
      are few studies, however, that have used appropriate meditational designs to
      provide causal evidence for the indirect effect of parenting on weight status via
      effects on child eating. A new approach is suggested for evaluating the
      effectiveness of intervention components and creating optimized intervention
      programs using a multiphase research design. Adoption of approaches such as the
      Multiphase Optimization Strategy (MOST) is necessary to provide the mechanistic
      evidence-base needed for the design and implementation of effective childhood
      obesity prevention programs.

PMID- 18346283
TI  - Double rupture of interventricular septum and free wall of the left ventricle, as
      a mechanical complication of acute myocardial infarction: a case report.
AB  - INTRODUCTION: Cardiac ruptures following acute myocardial infarction include
      rupture of the left ventricle free-wall, ventricular septal defects, and
      papillary muscle rupture. Double myocardial rupture is a rare complication of
      acute myocardial infarction (0.3 %) and the report of such cases is exclusively
      limited to a small series of autopsy studies. CASE PRESENTATION: In this report
      we present the unusual case of a 70-year-old woman with acute anteroseptal
      myocardial infarction, which was complicated by a combined rupture of the
      interventricular septum near the apex, and the free wall of the left ventricle
      with concomitant formation of a pseudoaneurysm. The double myocardial rupture was
      accidentally discovered 10 days later with echocardiography, when the patient,
      complaining only of mild exertional dyspnea, was hospitalized for a scheduled
      coronary angiography. The patient underwent successful surgical correction of the
      double myocardial rupture along with by-pass grafting. CONCLUSION: This report
      highlights the importance of comprehensive noninvasive predischarge diagnostic
      evaluation of all postinfarct patients, since serious and potentially life
      threatening complications might have not been suspected on clinical grounds.

PMID- 18346284
TI  - Transmission and quantification of verocytotoxin-producing Escherichia coli O157
      in dairy cattle and calves.
AB  - Data from a field study of 14 months duration in a naturally colonized dairy herd
      and data from an experiment with calves were used to quantify transmission of
      verocytotoxin-producing Escherichia coli (VTEC O157) in cattle. For the latter,
      two groups of 10 calves were randomly assigned and put out in one of two
      pastures. From each group, five animals were experimentally inoculated with 109
      c.f.u. O157 VTEC and, considered infectious, put back in their group. Each of the
      susceptible contact calves became positive within 6 days of being reunited. The
      estimate of the basic reproduction ratio (R0) in the experiment was 7.3 (95% CI
      3.92-11.5), indicating that each infectious calf will infect seven other calves
      on average during an assumed infectious period of 28 days in a fully susceptible
      population. The R0 among dairy cows appeared to be about 10 times lower (0.70,
      95% CI 0.48-1.04). After the transmission experiment, six contact-infected
      animals that were shedding continuously during the experiment were housed in a
      tie stall during winter. After 40 days, all six tested negative for O157 VTEC. In
      June, after a period of 34 weeks in which the heifers remained negative, they
      were put out in a clean and isolated pasture to observe whether they started
      shedding again. On each pasture that was infected with O157 VTEC during the
      transmission experiment the previous summer, newly purchased susceptible calves
      were placed. None of the heifers or calves started shedding during 14 weeks,
      indicating that both the heifers and the previously contaminated pasture did not
      function as reservoir of O157 VTEC.

PMID- 18346285
TI  - Record-linkage and capture-recapture analysis to estimate the incidence and
      completeness of reporting of tuberculosis in England 1999-2002.
AB  - In 1999 the Enhanced Tuberculosis Surveillance (ETS) system was introduced in the
      United Kingdom to strengthen surveillance of tuberculosis (TB). The aim of this
      study was to assess the use of record-linkage and capture-recapture methodology
      for estimating the completeness of TB reporting in England between 1999 and 2002.
      Due to the size of the TB data sources sophisticated record-linkage software was
      required and the proportion of false-positive cases among unlinked hospital
      derived TB records was estimated through a population mixture model. This study
      showed that record-linkage of TB data sources and cross-validation with
      additional TB-related datasets improved data quality as well as case
      ascertainment. Since the introduction of ETS observed completeness of
      notification in England has increased and the results were consistent with
      expected levels of under-notification. Completeness of notification estimated by
      a log-linear capture-recapture model was highly inconsistent with prior estimates
      and the validity of this methodology was further examined.

PMID- 18346286
TI  - Modelling alternative strategies for delivering hepatitis B vaccine in prisons:
      the impact on the vaccination coverage of the injecting drug user population.
AB  - Since 2001 hepatitis B vaccination has been offered to prisoners on reception
      into prisons in England and Wales. However, short campaigns of vaccinating the
      entire population of individual prisons have achieved high vaccination coverage
      for limited periods, suggesting that short campaigns may be a preferable way of
      vaccinating prisoners. A model is used that describes the flow of prisoners
      through prisons stratified by injecting status to compare a range of vaccination
      scenarios that describe vaccination on prison reception or via regular short
      campaigns. Model results suggest that vaccinating on prison reception can capture
      a greater proportion of the injecting drug user (IDU) population than the
      comparable campaign scenarios (63% vs. 55.6% respectively). Vaccination on prison
      reception is also more efficient at capturing IDUs for vaccination than
      vaccination via a campaign, although vaccination via campaigns may have a role
      with some infections for overall control.

PMID- 18346287
TI  - A statistical model investigating the prevalence of tuberculosis in New York City
      using counting processes with two change-points.
AB  - We considered a Bayesian analysis for the prevalence of tuberculosis cases in New
      York City from 1970 to 2000. This counting dataset presented two change-points
      during this period. We modelled this counting dataset considering non-homogeneous
      Poisson processes in the presence of the two-change points. A Bayesian analysis
      for the data is considered using Markov chain Monte Carlo methods. Simulated
      Gibbs samples for the parameters of interest were obtained using WinBugs
      software.

PMID- 18346288
TI  - The unexpected discovery of a focus of hepatitis C virus genotype 5 in a Syrian
      province.
AB  - Genotype 5 (G5) was initially discovered and is still mainly diagnosed in South
      Africa. No cases of G5 have ever been reported from the Middle East countries.
      The aim of the study was to determine the hepatitis C virus (HCV) genotype
      distribution in Syria and the prevalence of G5 in this country. Genotyping of HCV
      was performed in 636 consecutive HCV patients referred to eight medical centres
      in Syria over a 3-year period. Genotype 4 was the most frequent genotype (375
      patients, 59%) followed by genotype 1 (181 patients, 28.5%) and G5 (64 patients,
      10%). The majority of G5 patients (56 cases, 87%) live in the north of Syria,
      including 21 cases (33%) from Azaz, a small city close to Turkey. No obvious
      epidemiological reason for such high prevalence of G5 was found.

PMID- 18346289
TI  - Grommet insertion using a branula.
AB  - OBJECTIVE: To develop an easy method of performing myringotomy and grommet
      insertion, using minimal instruments. METHODS: An ear speculum and a branula were
      used. RESULTS: This method was found to be useful. CONCLUSION: An easy method of
      performing myringotomy and grommet insertion is proposed.

PMID- 18346290
TI  - Myringostapediopexy and myringolenticulopexy in mastoid surgery.
AB  - OBJECTIVE: To compare hearing results in patients undergoing myringostapediopexy
      or myringolenticulopexy in canal wall down mastoidectomy. STUDY DESIGN: Case
      series of one surgeon. A retrospective review of 83 consecutive mastoid cavity
      operations for primary cholesteatoma. Only those patients who had undergone
      either myringostapediopexy or myringolenticulopexy were included. SETTING:
      District general hospital. PATIENTS: Forty-two procedures were performed in 40
      patients. The mean age was 42 years old. The average follow up was 5.9 years.
      INTERVENTION: Seventeen patients underwent myringolenticulopexy (the incus head
      was excised, leaving the lenticular process attached to the stapes prior to graft
      placement) and 25 underwent myringostapediopexy (type III tympanoplasty). MAIN
      OUTCOME MEASURES: Audiometry three to six months after surgery, and status of
      mastoid cavity after a minimum follow up of one year. RESULTS: Comparison of post
      operative hearing results for the two groups showed a statistically significant
      hearing advantage for myringolenticulopexy (p = 0.029). In the
      myringolenticulopexy group, 92 per cent achieved a post-operative air-bone gap of
      less than 30 dB, compared with 62 per cent in the myringostapediopexy group. The
      mean post-operative air-bone gaps in the two groups were 17.5 and 24.7 dB,
      respectively. CONCLUSION: When surgically feasible, the technique of
      myringolenticulopexy is a useful method of preserving serviceable hearing in
      single-stage mastoid cavity surgery.

PMID- 18346291
TI  - Management of temporal bone meningo-encephalocoele.
AB  - Meningo-encephalocoele of the temporal bone, also known as fungus cerebri, is a
      rare occurrence in clinical practice. We present a series of 13 patients with
      chronic otitis media who suffered brain herniation into the mastoid cavity. We
      also discuss the presentation and management of brain herniation with or without
      cerebrospinal fluid leak. STUDY DESIGN: Retrospective. METHODS: Among 963 cases
      undergoing revision mastoid surgery, 13 patients suffered brain herniation. These
      cases were identified and analysed. RESULTS: All 13 patients' initial diagnosis
      was chronic suppurative otitis media with cholesteatoma, and all had undergone
      previous mastoid surgery resulting in a defect in the tegmen and weakening of the
      dura mater. The revision procedures performed included 10 (76.9 per cent)
      modified radical mastoidectomies without ossicular chain reconstruction and one
      (7.6 per cent) modified radical mastoidectomy with ossicular chain
      reconstruction; two (15.3 per cent) patients required a blind sac closure. Brain
      herniation and/or cerebrospinal fluid leak were repaired by a transmastoid +/-
      minicraniotomy procedure. CONCLUSIONS: Injury to the tegmen and dura should be
      avoided during surgery for chronic middle-ear disease. Cerebrospinal fluid leaks,
      if encountered, should be managed in the same surgical session. The transmastoid
      approach is helpful in repairing defects smaller than 1 cm in diameter, whereas
      the combined transmastoid-minicraniotomy approach provides good access when
      closing defects larger than 1 cm in diameter and also enables auto-calvarial
      grafting.

PMID- 18346292
TI  - A double-blind, randomized, placebo-controlled prophylaxis trial of oxcarbazepine
      as adjunctive treatment to lithium in the long-term treatment of bipolar I and II
      disorder.
AB  - We evaluated the prophylactic efficacy and the long-term tolerability of
      oxcarbazepine administration in the treatment of bipolar I and II disorder as an
      adjunctive therapy to lithium. We conducted a 52-wk, double-blind, randomized,
      placebo-controlled, parallel-group, multicentre, clinical trial. Bipolar I and II
      DSM-IV outpatients, having had two or more episodes in the last year, but
      currently being in remission, were randomly assigned on a 1:1 ratio to
      oxcarbazepine (n=26) or placebo (n=29) as adjuncts to ongoing treatment with
      lithium. The primary efficacy variable was the length of the remission period
      assessed by means of the Young Mania Rating Scale (YMRS) and Montgomery-Asberg
      Depression Rating Scale (MADRS). Other assessments were the Clinical Global
      Impression (CGI-BP-M), functional activity (GAF), anxiety (HAMA) and
      impulsiveness (BIS-11). The average time until first recurrence of any type was
      19.2+/-13.9 wk and 18.6+/-17.0 wk for oxcarbazepine and placebo respectively
      (p=0.315). Ten (38.46%) patients had a recurrence of any kind in the
      oxcarbazepine group vs. 17 (58.62%) in the placebo group (p=0.1354). There was a
      trend for depressive episodes being less likely in the oxcarbazepine group
      compared to the placebo group (11.54% and 31.03% respectively, p=0.085), and for
      better functionality with the GAF (p=0.074). Impulsivity was significantly better
      prevented by oxcarbazepine (p=0.0443). Overall, oxcarbazepine was well tolerated.
      This pilot, randomized clinical trial, suggests that oxcarbazepine might have
      some prophylactic efficacy with regards to impulsivity and perhaps mood episodes
      in patients taking lithium, although further, adequately powered controlled
      trials are needed to confirm these findings.

PMID- 18346293
TI  - The effect of 12-week open-label memantine treatment on cognitive function
      improvement in patients with alcohol-related dementia.
AB  - There is compelling evidence that alcohol-induced neurotoxicity is related to
      glutamate excitotoxicity. It was hypothesized that the low-affinity NMDA receptor
      antagonist memantine would improve the cognitive function of patients with
      alcoholic dementia. The aim of this study was to test this hypothesis and to
      evaluate the effect of memantine on the cognitive improvement of patients with
      alcohol-related dementia (ARD). The study was designed as a 12-wk open-label
      study investigating the efficacy of 20 mg memantine, a low-affinity NMDA receptor
      antagonist, as a treatment for cognitive and behavioural problems in 19 patients
      with probable ARD according to the criteria for ARD proposed by Oslin and
      colleagues. The CERAD-K (Consortium to Establish a Registry for Alzheimer's
      Disease - Korean version) and several clinical assessment scales were completed
      before and after the 12-wk memantine treatment period. Significant improvements
      in the mean scores from baseline to final assessment were observed in the Global
      Deterioration Scale (p<0.05), Brief Psychiatric Rating Scale (p<0.01), Geriatric
      Quality of Life - Dementia scale (p<0.01) and Neuropsychiatric Inventory (p<0.01)
      at the end of week 12. The CERAD-K subscales of word list recall (p<0.05), word
      list recognition (p<0.05), time orientation (p<0.01), drawing an interlocking
      pentagon (p<0.05), and the total MMSE-K (Mini Mental State Examination - Korean
      version) scores (p<0.01) of the patients all showed significant improvement
      following the memantine trial. In this open-label study, patients with ARD
      treated with 20 mg/d memantine for 12 wk showed improvement on global cognition,
      quality of life and behavioural symptoms. The result of this study suggests the
      possible usefulness of memantine for the treatment of ARD. As this was an open
      label study, the possibility that participants improved cognitively on their own
      due to protracted abstinence from alcohol cannot be discounted.

PMID- 18346294
TI  - Tricyclic antidepressants (TCA) may improve atomoxetine's efficacy.

PMID- 18346295
TI  - Quetiapine in post-transplant acute mania/bipolar disorder NOS.

PMID- 18346296
TI  - Actinobacillus pleuropneumoniae vaccines: from bacterins to new insights into
      vaccination strategies.
AB  - With the growing emergence of antibiotic resistance and rising consumer demands
      concerning food safety, vaccination to prevent bacterial infections is of
      increasing relevance. Actinobacillus pleuropneumoniae is the etiological agent of
      porcine pleuropneumonia, a respiratory disease leading to severe economic losses
      in the swine industry. Despite all the research and trials that were performed
      with A. pleuropneumoniae vaccination in the past, a safe vaccine that offers
      complete protection against all serotypes has yet not reached the market.
      However, recent advances made in the identification of new potential vaccine
      candidates and in the targeting of specific immune responses, give encouraging
      vaccination perspectives. Here, we review past and current knowledge on A.
      pleuropneumoniae vaccines as well as the newly available genomic tools and
      vaccination strategies that could be useful in the design of an efficient vaccine
      against A. pleuropneumoniae infection.

PMID- 18346297
TI  - Antigen-independent priming: a transitional response of bovine gammadelta T-cells
      to infection.
AB  - Analysis of global gene expression in immune cells has provided unique insights
      into immune system function and response to infection. Recently, we applied
      microarray and serial analysis of gene expression (SAGE) techniques to the study
      of gammadelta T-cell function in humans and cattle. The intent of this review is
      to summarize the knowledge gained since our original comprehensive studies of
      bovine gammadelta T-cell subsets. More recently, we have characterized the
      effects of mucosal infection or treatment with microbial products or mitogens on
      gene expression patterns in sorted gammadelta and alphabeta T-cells. These
      studies provided new insights into the function of bovine gammadelta T-cells and
      led to a model in which response to pathogen-associated molecular patterns
      (PAMPs) induces 'priming' of gammadelta T-cells, resulting in more robust
      responses to downstream cytokine and/or antigen signals. PAMP primed gammadelta T
      cells are defined by up-regulation of a select number of cytokines, including
      MIP1alpha and MIP1beta, and by antigens such as surface IL2 receptor alpha (IL
      2Ralpha) and CD69, in the absence of a prototypic marker for an activated
      gammadelta T-cell, IFN-gamma. Furthermore, PAMP primed gammadelta T-cells are
      more capable of proliferation in response to IL-2 or IL-15 in the absence of
      antigen. PAMPs such as endotoxin, peptidoglycan and beta-glucan are effective
      gammadelta T-cell priming agents, but the most potent antigen-independent priming
      agonists defined to date are condensed oligomeric tannins produced by some
      plants.

PMID- 18346298
TI  - Frequentist and Bayesian approaches to prevalence estimation using examples from
      Johne's disease.
AB  - Although frequentist approaches to prevalence estimation are simple to apply,
      there are circumstances where it is difficult to satisfy assumptions of
      asymptotic normality and nonsensical point estimates (greater than 1 or less than
      0) may result. This is particularly true when sample sizes are small, test
      prevalences are low and imperfect sensitivity and specificity of diagnostic tests
      need to be incorporated into calculations of true prevalence. Bayesian approaches
      offer several advantages including direct computation of range-respecting
      interval estimates (e.g. intervals between 0 and 1 for prevalence) without the
      requirement of transformations or large-sample approximations, direct
      probabilistic interpretation, and the flexibility to model in a straightforward
      manner the probability of zero prevalence. In this review, we present frequentist
      and Bayesian methods for animal- and herd-level true prevalence estimation based
      on individual and pooled samples. We provide statistical methods for detecting
      differences between population prevalence and frequentist methods for sample size
      and power calculations. All examples are motivated using Mycobacterium avium
      subspecies paratuberculosis infection and we provide WinBUGS code for all
      examples of Bayesian estimation.

PMID- 18346299
TI  - Prevalence and severity of external auditory exostoses in breath-hold divers.
AB  - OBJECTIVE: To explore the prevalence and severity of external auditory exostoses
      in a population of experienced breath-hold divers, and to compare these to the
      same parameters within surfing and self-contained underwater breathing apparatus
      diving populations. DESIGN: A stepwise, multiple regression analysis of cross
      sectional data examining the relative contributions of sea surface temperature,
      latitude of exposure and years of exposure to the prevalence and severity of
      stenosis due to external auditory exostoses. A chi-square analysis of the
      prevalence and severity of external auditory exostosis stenosis in the breath
      hold divers was compared with previously published data for surfers and self
      contained underwater breathing apparatus divers. SUBJECTS: Seventy-six male and
      thirty-five female breath-hold divers attending an international 'freedive'
      competition completed a questionnaire describing aquatic sports habits, geography
      of participation and symptomatology. Those completing the questionnaire (111/154
      attendees) were examined otoscopically for evidence of external auditory
      exostoses. Images were digitally recorded, scored and graded. RESULTS: Exostoses
      were evident in 87.7 per cent of the 204 ears scored and graded for severity of
      stenosis due to external auditory exostoses. The prevalence of exostoses was no
      different from that found in previous studies of surfers and self-contained
      underwater breathing apparatus divers (p = 0.101). However, the pattern of
      affliction was more similar to that found in surfers. The severity of exostoses
      was significantly less than that found in surfing populations (p < or = 0.001 to
      0.007), but greater than that found in self-contained underwater breathing
      apparatus diving populations (p < or = 0.001). Sea surface temperature at the
      location of open-water exposure was the most significant predictor of the
      prevalence and severity of external auditory exostoses in breath-hold divers (p =
      0.019). CONCLUSION: The prevalence and severity patterns of stenosis due to
      external auditory exostoses in breath-hold divers are more similar to previously
      published results for surfing populations than to previously published results
      for self-contained underwater breathing apparatus diving populations. In breath
      hold divers, sea surface temperature is the strongest predictor of severity of
      stenosis due to external auditory exostoses.

PMID- 18346300
TI  - Radiographic properties of injected calcium hydroxylapatite: potential false
      positive findings on positron emission tomography.
AB  - OBJECTIVES: To describe the positron emission tomography and computed tomography
      features of injected calcium hydroxylapatite, and to discuss how these may be
      mistaken for malignancy. CASE REPORT: Positron emission tomography is now readily
      employed in the staging and monitoring of patients with head and neck carcinoma.
      Concomitant with the growing use of this modality has been the increasing
      popularity of injected calcium hydroxylapatite to treat glottic incompetence
      secondary to vocal fold paralysis or following partial laryngectomy. A patient
      developed aspiration following near-total laryngectomy and subsequently underwent
      injection of calcium hydroxylapatite, with effective resolution of the
      aspiration. The patient underwent positron emission tomography scanning as part
      of routine tumour surveillance; this showed intense tracer uptake at the site of
      injection, and this pattern persisted for one year following injection.
      CONCLUSIONS: As injectable calcium hydroxylapatite becomes more widely used,
      especially in the treatment of patients with a history of head and neck cancer,
      physicians should be aware it may cause a potentially misleading, false positive
      positron emission tomography finding.

PMID- 18346301
TI  - Modernization or cultural maintenance: the practice of consanguineous marriage in
      Iran.
AB  - Consanguineous marriage has been the culturally preferred form of marriage in
      Iran. This paper examines the extent to which education, urbanization and changes
      in modes of economic production have affected the incidence of consanguineous
      marriage and attitudes towards consanguineous marriages. The 2002 Iran Fertility
      Transition Survey conducted in the four provinces of Gilan, Sistan and
      Baluchistan, Yazd and West Azarbaijan provides information on the degree of
      relationship of marriage partners from around 6550 ever-married women aged 15-49.
      Attitudinal data were also obtained. Overall, the level of marriage to biological
      relatives ranged from 23% in Gilan to 78% in Sistan and Baluchistan. The paper
      finds that the practice of marriage to biological relatives has remained
      surprisingly resilient in the face of modernizing influences and that ethnicity,
      province and area of residence remain important determinants. On the other hand,
      attitudes have shifted towards marriage with a non-relative. Anthropological
      research would illuminate the processes of consanguineous marriage in Iran.

PMID- 18346302
TI  - Body height in relation to rural-urban migration in Poland.
AB  - A survey was conducted among 2800 students studying in Wroclaw, Poland. The
      questionnaire included questions on the body height of the students and their
      parents, and place of residence and migration patterns of the students
      themselves, their parents and their grandparents. Body height in both students
      and their parents was positively correlated with the size of their place of
      residence. This was particularly true for male students and their fathers. Body
      height in students and parents from mobile families was not significantly
      different from that of their peers from non-mobile families. Body height in
      mobile individuals was generally between that of non-mobile individuals from
      rural areas and that of non-mobile individuals from large urban centres. Students
      from families that had migrated from smaller urban centres to larger ones were
      taller than students from families that had migrated from rural areas to urban
      centres. Body height in students was also correlated with the kind of migration
      that took place. In the students' mothers, body height was higher if the maternal
      grandparents moved from smaller urban centres to larger urban centres than if the
      maternal grandparents moved from rural areas to urban centres. In female
      students, body height depended on whether their mothers had migrated from smaller
      places of residence to larger places of residence, but was not affected by the
      degree of migration. Intra-generational migration during the generation of the
      students' grandparents was associated with increased body height in the students'
      mothers. On the other hand, intergenerational migration during the generations of
      the students' grandparents and parents was associated with increased body height
      in the students' fathers and in female students. Body height was not a reliable
      indicator of whether an individual migrated from rural areas to Wroclaw. Far more
      reliable indicators were the size of the place the student lived their whole life
      and whether the family had lived in an urban environment for at least two
      generations.

PMID- 18346303
TI  - Association of different obesity indices with blood pressure and blood lipids in
      children and adolescents.
AB  - The aim of the present study was to compare individual associations of BMI,
      triceps skinfold (TSF), waist circumference (WC) and percentage fat mass (%FM)
      with blood pressure (BP) and blood lipids in children and adolescents. Cross
      sectional data on BMI, TSF, WC, %FM as well as on BP, TAG and HDL were analysed
      in 4220 (BP) and 729 (lipids) 9-11-year-old children and 3174 (BP) and 536
      (lipids) 13-16-year-old adolescents as part of the Kiel Obesity Prevention Study.
      All obesity indices were similarly associated with BP and blood lipids. In girls,
      WC had closer correlations to BP than BMI (systolic BP: 0.27 and 0.24 for BMI,
      0.34 and 0.28 for WC in 9-11- and 13-16-year-olds). Subjects with an obesity
      index > or = 90th percentile had higher prevalences of elevated BP and blood
      lipids than subjects with a normal index. In children with normal BMI or WC, an
      additionally elevated second obesity index was associated with a 2.5-7.4-fold
      higher prevalence of high BP when compared with children with normal indices. In
      adolescents, an elevated WC plus an elevated second obesity index was associated
      with a 2.6-8.2-fold higher prevalence of high BP when compared with adolescents
      with an elevated WC plus a normal second index. We conclude that (i) both BMI and
      WC are appropriate to estimate CVD risk, (ii) the use of a second obesity index
      is recommended in children with normal BMI or normal WC as well as in adolescents
      with elevated WC and (iii) all obesity indices seemed to be appropriate for risk
      assessment.

PMID- 18346304
TI  - Validity and reliability of body composition analysers in children and adults.
AB  - We tested the validity and reliability of the BioSpace InBody 320, Omron and Bod
      eComm body composition devices in men and women (n 254; 21-80 years) and boys and
      girls (n 117; 10-17 years). We analysed percentage body fat (%BF) and compared
      the results with dual-energy X-ray absorptiometry (DEXA) in adults and compared
      the results of the InBody with underwater weighing (UW) in children. All body
      composition devices were correlated (r 0.54-0.97; P< or =0.010) to DEXA except
      the Bod-eComm in women aged 71-80 years (r 0.54; P=0.106). In girls, the InBody
      %BF was correlated with UW (r 0.79; P< or =0.010); however, a more moderate
      correlation (r 0.69; P< or =0.010) existed in boys. Bland-Altman plots indicated
      that all body composition devices underestimated %BF in adults (1.0-4.8 %) and
      overestimated %BF in children (0.3-2.3 %). Lastly, independent t tests revealed
      that the mean %BF assessed by the Bod-eComm in women (aged 51-60 and 71-80 years)
      and in the Omron (age 18-35 years) were significantly different compared with
      DEXA (P< or =0.010). In men, the Omron (aged 18-35 years), and the InBody (aged
      36-50 years) were significantly different compared with DEXA (P=0.025; P=0.040
      respectively). In addition, independent t tests indicated that the InBody mean
      %BF in girls aged 10-17 years was significantly different from UW (P=0.001).
      Pearson's correlation analyses demonstrated that the Bod-eComm (men and women)
      and Omron (women) had significant mean differences compared with the reference
      criterion; therefore, the %BF output from these two devices should be interpreted
      with caution. The repeatability of each body composition device was supported by
      small CV (<3.0 %).

PMID- 18346305
TI  - Dietary single cell protein reduces fatty liver in obese Zucker rats.
AB  - There is growing evidence that dietary proteins may interfere with lipid
      metabolism. We therefore examined the effects of feeding obese Zucker rats a
      single cell protein (SCP) with low ratios of methionine:glycine and
      lysine:arginine for 6 weeks. SCP feeding reduced the hepatic steatosis and
      lowered the plasma transaminase levels when compared with casein-fed rats
      (controls). The fatty acid oxidation was increased in liver mitochondria and
      peroxisomes, whereas the activities of enzymes involved in lipogenesis and TAG
      biosynthesis were unaffected. SCP feeding affected the fatty acid composition of
      liver lipids and plasma, and reduced the mRNA levels of the fatty acid
      desaturases. The decreased gene expression of stearoyl-CoA desaturase suggested
      that the fatty acids were directed towards oxidation rather than esterification
      as TAG. The decreased mRNA levels of VLDL-receptor and lipoprotein lipase in the
      liver after SCP feeding suggested that the uptake of TAG-rich lipoprotein to the
      liver was decreased. To conclude, the reduced fatty liver by SCP feeding may be
      caused by the increased capacity for fatty acid beta-oxidation in the liver,
      combined with changed fatty acid composition and possibly a reduced hepatic
      clearance of circulating VLDL. An increased awareness of the effect of dietary
      proteins on lipid metabolism could be of relevance in future dietary treatment of
      non-alcoholic fatty liver disease.

PMID- 18346306
TI  - Physiological concentrations of short-chain fatty acids immediately suppress
      colonic epithelial permeability.
AB  - Colonic fermentation products, SCFA, have various effects on colonic functions.
      Here, we found that physiological concentrations of SCFA immediately promote
      epithelial barrier function in the large intestine. Solutions of mixed and
      individual SCFA were applied to the caecal walls mounted on Ussing-type chambers.
      Transepithelial electrical resistance (TER) increased rapidly and reached a peak
      35 % higher than that in the control specimen within 10 min post application of
      the SCFA mixture (80 acetate, 40 propionate, 20 butyrate (mmol/l)). The Lucifer
      yellow permeability, a paracellular transport marker, was dose-dependently
      reduced by the mixed SCFA, acetate and propionate solutions. Inhibition of
      monocarboxylate transporter-1 did not influence the increase in TER with acetate;
      however, lowering the pH (from 7.5 to 5.5) clearly enhanced the effect of
      acetate. Non-metabolizable, bromo and chloro derivatives of SCFA also increased
      TER. These results suggest that passive diffusion of SCFA is dominant and the
      metabolism of SCFA is not required for the promotive effect of SCFA on barrier
      function. We also observed that individual SCFA dose-dependently increased TER in
      T84 and Caco-2 cells, which indicates that SCFA directly stimulate epithelial
      cells. Depletion of membrane cholesterol and inhibitors of phosphatidylinositol-3
      kinase and Gq protein attenuated the acetate-mediated promotive effect. Finally,
      we found that the mucosal application of the SCFA mixture dose-dependently
      suppressed [3H] mannitol transport from the caecal lumen to the mesenteric blood
      in the anaesthetized rats. We conclude that physiological concentrations of SCFA
      immediately enhance barrier function of the colonic epithelium through
      cholesterol-rich microdomain in the plasma membrane.

PMID- 18346307
TI  - Food-chain selenium and human health: spotlight on speciation.
AB  - There is a growing appreciation that it is not just the total intake of dietary
      Se that is important to health but that the species of Se ingested may also be
      important. The present review attempts to catalogue what is known about Se
      species in foods and supplements and the health effects in which they are
      implicated. The biosynthetic pathways involved in Se assimilation by plants and
      the way in which Se species are metabolised in animals are presented in order to
      give an insight into the species likely to be present in plant and animal foods.
      Known data on the species of Se in the food chain and in food supplements are
      tabulated along with their concentrations and the analytical methodology used.
      The latter is important, since identification that is only based on retention
      time matching with authentic standards must be considered as tentative: for
      evidence of structural confirmation, fragmentation of the molecular ion in
      addition to MS data is required. Bioavailability, as normally defined, is higher
      for organic Se species. Health effects, both beneficial and toxic, thought to be
      associated with specific Se species are described. Potent anti-tumour effects
      have been attributed to the low-molecular-weight species, Se-methyl
      selenocysteine and its gamma-glutamyl-derivative, found in a number of edible
      plants of the Allium and Brassica families. There remain considerable gaps in our
      knowledge of the forms of Se that naturally occur in foods. Without adequate
      knowledge of Se speciation, false conclusions may be drawn when assessing Se
      requirements for optimal health.

PMID- 18346308
TI  - Food-chain selenium and human health: emphasis on intake.
AB  - Following the publication of the landmark trial of Clark et al. in 1996 that
      appeared to show that Se could reduce the risk of cancer, awareness of the
      importance of Se to human health has markedly increased. As a result, there is
      now much more aggressive marketing of Se supplements and functional foods, even
      in situations where additional consumption of Se is inappropriate. The present
      review addresses how Se gets into the food chain, the wide variability in Se
      content of foods and the very different levels of intake between countries and
      regions. Though it is clear that there are adverse consequences for health of
      both deficient and excessive intake, health effects at intermediate levels of
      intake are less certain. Thus it is difficult to define optimal intake which
      depends on a large number of factors, such as which functions of Se are most
      relevant to a particular disease state, which species of Se is most prominent in
      the Se source, which health condition is being considered, the adequacy or
      otherwise of intake of other nutrients, the presence of additional stressors, and
      lastly whether the ability to make selenoproteins may be compromised. These
      complexities need to be understood, particularly by policy makers, in order to
      make informed judgments. Potential solutions for increasing Se intake, where
      required, include agronomic biofortification and genetic biofortification or, for
      individuals, increased intake of naturally Se-rich foods, functional foods or
      supplements. The difficulties of balancing the risks and benefits in relation to
      Se intake are highlighted.

PMID- 18346309
TI  - Breakfast skipping is associated with differences in meal patterns, macronutrient
      intakes and overweight among pre-school children.
AB  - OBJECTIVES: To examine the association between skipping breakfast, daily energy,
      macronutrients and food intakes, and BMI in pre-school children. DESIGN: A cross
      sectional study using information on children's food consumption and measured
      height and weight. Energy and macronutrient intakes of the children were derived
      from parent/day-care attendant's responses to 24 h recall interviews and eating
      behaviour questionnaires. SETTING: Data obtained from a representative sample (n
      2,103) of children born in Quebec (Canada) in 1998. SUBJECTS: One thousand five
      hundred and forty-nine children, with a mean age of 49 (sd 3.12) months. RESULTS:
      Ten per cent of children ate breakfast on fewer than 7 days per week. This
      behaviour was associated with a lower diet quality and concentrated energy
      intakes through higher protein intakes at lunch and the consumption of snacks
      higher in energy and carbohydrate in the afternoon and evening; yet total daily
      energy intakes were not significantly different from those of pre-school children
      who ate breakfast every day. Breakfast skippers' mean BMI increased as intake of
      energy, carbohydrates or servings of grain products increased; however, this was
      not the case for breakfast eaters. When Cole's cut-off for overweight/obesity was
      used, overweight/obesity in breakfast skippers was related to the dinner-time
      consumption of approximately 3,000 kJ (700 kcal) or more for energy intake,
      approximately 100 g or more of carbohydrates, or approximately 3 servings or more
      of grain products. CONCLUSIONS: Eating breakfast every day is associated with
      having a healthy body weight, likely due to a more even distribution of energy
      intake across meals throughout the day.

PMID- 18346310
TI  - Workforce development in South Africa with a focus on public health nutrition.
AB  - OBJECTIVES: The present paper aims to review and report on the current and
      predicted future public health nutrition workforce in South Africa. Additionally,
      it examines ways in which the Department of Health (DOH) is striving to meet the
      increasing burden of nutrition-related diseases in South Africa. METHODS: The
      primary sources of data used for the review were reports from the Census office,
      South African health reviews, mortality and morbidity statistics, and documents
      from the Health Professions Council of South Africa. RESULTS: There are fewer
      than 2000 registered dietitians in South Africa and fewer than 600 of them work
      in the public health sector. Furthermore, professional nurses - who are the
      backbone of the primary health-care system and deliver the rudiments of basic
      nutritional care - are not being trained in sufficient numbers to meet population
      growth; in 2004 there was only one nurse per 4000 persons. This situation is
      aggravated by the growing burden of conditions associated with both overnutrition
      and undernutrition, as well as the enormous demands of the HIV/AIDS epidemic. The
      DOH is striving to meet these increasing needs by means of the Integrated
      Nutrition Programme as well as a National Human Resources Plan which includes
      numerous strategies to improve the quantity and quality of health professionals'
      training, including dietitians and nutritionists. This plan includes the
      objective of increasing the public health nutrition workforce to more than 250
      newly trained dietitians and nutritionists per annum by 2010.

PMID- 18346311
TI  - Comparison of self-reported survey (SHIELD) versus NHANES data in estimating
      prevalence of dyslipidemia.
AB  - OBJECTIVES: The study purpose was to compare the prevalence of dyslipidemia
      between a self-reported survey, Study to Help Improve Early evaluation and
      management of risk factors Leading to Diabetes (SHIELD), and survey and
      laboratory data from National Health and Nutrition Examination Survey (NHANES
      1999-2002). METHODS: A SHIELD questionnaire was mailed to 200,000 households
      representative of US adult population (64% response, n = 211,097 individuals) and
      included if ever diagnosed with diabetes, high blood pressure or cholesterol
      problems, high total cholesterol (TC), high bad cholesterol (LDL-C), low good
      cholesterol (HDL-C), or high triglycerides (TG). In NHANES using a combination of
      interviewer-administered survey and clinical and laboratory data, dyslipidemia
      was defined as any one of: TC > or = 240 mg/dL or diagnosis of high cholesterol;
      TG > 200 mg/dL; LDL-C > or = 160 mg/dL; or HDL-C < 40 mg/dL. NHANES diabetes
      mellitus definition was doctor diagnosis or fasting glucose > 125 mg/dL and
      hypertension was elevated blood pressure or taking anti-hypertensive medication.
      Prevalence of dyslipidemia was determined for SHIELD in 2004 and compared to
      NHANES 1999-2002. Prevalence of diabetes and hypertension was estimated for
      broader contextual comparison within cardiometabolic diseases. RESULTS: In
      contrast to the prevalence of diabetes (8% in SHIELD and 9% in NHANES, p < 0.01)
      and hypertension (23% in SHIELD and 29% in NHANES, p < 0.01), dyslipidemia was
      reported only half as frequently in SHIELD (26%) as in NHANES (53%), p < 0.01.
      Components of dyslipidemia were uniformly less in SHIELD than NHANES: high TC =
      17 vs. 35%, high LDL-C = 10 vs. 14%, high TG = 7 vs. 17% and low HDL-C = 5 vs.
      24%; all comparisons p < 0.01. LIMITATIONS: Differences in survey methodology,
      non-response and timing may have impacted the comparison of SHIELD to NHANES.
      CONCLUSIONS: Dyslipidemia prevalence was lower in self-reported SHIELD than the
      objectively assessed NHANES, with especially low self-report of high TG and low
      HDL-C. Self-reported prevalence of dyslipidemia may under-report the prevalence
      based on laboratory data.

PMID- 18346313
TI  - [Standardized diagnosis and treatment for inflammatory bowel disease].

PMID- 18346314
TI  - [Pay attention to the complications encountered in capsule endoscopy].

PMID- 18346315
TI  - [Communication and cooperation between neurology and psychology: narrowing the
      gap].

PMID- 18346316
TI  - [Eradication of H. pylori in management of dyspepsia].

PMID- 18346317
TI  - [The application of Montreal classification in inflammatory bowel disease].
AB  - OBJECTIVE: To investigate the clinical features of Crohn's disease (CD) and
      ulcerative colitis (UC) according to the Montreal classification. METHODS: The
      clinical data of 110 cases of CD or UC were reviewed. The age at diagnosis,
      location and clinical behavior were assessed with the Montreal criteria. RESULTS:
      CD patients diagnosed at an age younger than 16 years were rare (3.6%), the
      majority of the CD patients was diagnosed at 17 - 40 years old (65.5%). Although
      ileocolon lesions were most common in the patients diagnosed at 17 - 40 years old
      (37.3%), yet ileum lesions were a little more than those of other parts of
      digestive tract in the patients diagnosed after 40 years old (14.5%), the
      difference was not significant (P = 0.054). Stricture frequently occurred
      (50.4%), especially when the lesions were located at ileum or ileocolon.
      Perforation rarely happened (5.3%). There was no significant difference between
      different location groups for clinical behaviors (P = 0.096). The incidence of
      stricture or perforation was almost same among different age groups (P = 0.984).
      UC patients mostly presented with mild or moderate symptoms even in the group
      with extensive lesion. UC patients with severe symptoms were rare (6.8%). There
      was no significant difference in severity between the groups with different
      extent of lesion (P = 0.056). CONCLUSIONS: The majority of CD patients was
      diagnosed at 17 - 40 years old. Stricture is much more than perforation,
      penetrating, occurring mostly at ileum. UC patients mostly present mild or
      moderate symptoms, no matter how extensive the lesion is. The extent of the
      lesion detected with colposcopic examination is not correlated to the severity of
      clinical manifestations.

PMID- 18346318
TI  - [Expression and significance of mucosal beta-defensin-2, TNFalpha and IL-1beta in
      ulcerative colitis].
AB  - OBJECTIVE: To investigate the expression and significance of human beta-defensin
      2 (HBD2), TNFalpha and IL-1beta in ulcerative colitis (UC). METHODS: Thirty-five
      patients with active UC diagnosed by the department of gastroenterology in West
      China Hospital were included in this study. Ulcerative colitis disease activity
      index (UCAI) was assessed and the pathological grades of UC were classified.
      Immunohistochemistry assay and real-time quantitative PCR were used for the
      expression of HBD2, TNFalpha, IL-1beta in colonic mucosa of UC. RESULTS: Among
      the 35 patients with UC, 10 cases were mild, 13 moderate and 12 severe. Of the 35
      cases, there were 11 with grade I, 13 grade II and 11 grade III lesion according
      to Truelove criteria. The score of UCAI had positive correlation with
      pathological grading (r = 0.890, P < 0.01). The expressions of HBD2, TNFalpha, IL
      1beta in colonic mucosa of UC with immunohistochemistry and real-time
      quantitative PCR were significantly higher than those in healthy control (P <
      0.05); the expressions increased gradually with the severity of pathological
      grade and there was a higher expression of them in inflamed area than in non
      inflamed (P < 0.05). A good positive correlation was also found between HBD2 and
      other inflammatory cytokines. CONCLUSIONS: It is shown that there is a higher
      expression of HBD2 in colonic mucosa as compared with healthy control, a higher
      expression of it in inflamed area than in non-inflamed area and a positive
      correlation of expression between HBD2 and pro-inflammatory cytokines such as
      TNFalpha and IL-1beta, implying that HBD2 and pro-inflammatory cytokines are
      interdependent and interactive playing an important role in magnifying and
      aggravating inflammatory injury in UC.

PMID- 18346319
TI  - [The role of OX40 in CD4+ T cells cytokines production in ulcerative colitis].
AB  - OBJECTIVE: To investigate the expression of OX40 on CD(4)(+) T cells in patients
      with ulcerative colitis (UC) and the role of OX40/OX40L interaction for the
      cytokine production of lamina propria (LP)-CD(4)(+) T cells from UC. METHODS: LP
      CD(4)(+) T cells were purified. The expression of OX40 molecule was measured with
      FACS. LP-CD(4)(+) T cells were cultured with different stimuli and proliferation
      was assessed. The cytokines concentrations of the culture supernatant were
      detected. RESULTS: No difference of the OX40 expression was observed among the
      CD(4)(+) T cells from peripheral blood (PB) of UC patients, LP of non
      inflammatory colonic tissue in UC patients and control PB. However, the
      expression of OX40 was significantly higher on LP-CD(4)(+) T cells from
      inflammatory colonic tissue in UC patients. In vitro culture with antigen
      presenting cells, the levels of IFNgamma and TNFalpha secreted by LP-CD(4)(+) T
      cells from the inflammatory colonic tissue were significantly higher than those
      from the non-inflammatory colonic tissue (both P < 0.01). The levels of IFNgamma
      and TNFalpha secreted by LP-CD(4)(+) T cells from the inflammatory colonic tissue
      were further increased by anti-OX40 MoAb stimulation, but suppressed
      significantly by adding anti-OX40L MoAb (compared with non stimulation, P < 0.01,
      respectively). The IFNgamma and TNFalpha secretion of the LP-CD(4)(+) T cells
      from the non-inflammatory colonic tissue were not significantly different with
      and without anti-OX40 or anti-OX40L MoAbs stimulation. IL-4 and IL-10 produced by
      LP-CD(4)(+) T cells from the inflammatory or non-inflammatory colonic tissue were
      not significantly changed when adding different stimuli. CONCLUSIONS: OX40 is
      highly expressed on LP-CD(4)(+) T cells from inflammatory colonic tissue in
      patients with UC. Anti-OX40L MoAb can inhibit the proinflammatory cytokines
      secreted by these cells. It is indicated that OX40(+) T cells are involved in the
      immunopathological process in UC and blockage of the interaction of OX40 and
      OX40L is a new strategy to be considered for the treatment of the disease.

PMID- 18346320
TI  - [An analysis of failure and safety profiles of capsule endoscopy].
AB  - OBJECTIVE: To analyse the incidence of technical breakdown and clinical problem
      leading to the failure of capsule endoscopy examination and their influence on
      the diagnosis and to evaluate its feasibility and safety in special patient
      population. METHODS: A retrospective study of 300 consecutive patients referred
      to Renji Hospital for evaluation of suspected small bowel diseases between May
      2002 and May 2006 was done. This included 300 consecutive patients. The median
      age of the patients was 51 y (range, 3 - 91 y). The young children group was
      defined as less than 10 years and the elderly group as more than 80 years.
      Technical problems were those related to the functioning of the equipment and
      clinical problems were those related to the patient. The incidence and the type
      of above-mentioned events and their influence on the diagnosis were analyzed. The
      safety and feasibility of the capsule endoscopy procedure were evaluated in the
      young children group, elderly group and patients with pacemakers, gastrectomy and
      Billroth II gastrojejunostomy, intestinal diverticula, Crohn's disease and polyp
      of small intestine. RESULTS: A total of 300 patients were involved. The incidence
      of technical problems was 1.3%, including one case of failing in activating the
      capsule, one case of failing in loading the data and two cases of short life of
      battery. Failure of diagnosis was encountered in two cases. The incidence of
      clinical problems was 33.0% (99 cases) and they caused 35.4% (35 cases) failure
      of diagnosis in the 99 cases. Three patients in the young children group were
      unable to swallow the capsule and endoscope-guided overtube technique was used
      with success in all. In the elderly group, the incidence of capsule retaining in
      the oesophagus and stomach was as high as 23.0%. In two patients with pacemaker
      no interference between pacemaker and capsule was detected. In two patients with
      Billroth II gastrojejunostomy no capsule retention occurred. In 16 patients with
      diverticulum, capsule retention occurred in 1 case (6.0%). In 42 patients with
      Crohn's disease, capsule retention occurred in 5 cases. No acute gastrointestinal
      obstruction was found in the 42 patients with Crohn's disease and in 5 patients
      with polyp of small intestine. CONCLUSIONS: With capsule endoscopy technical
      mistakes causing failure were very rare. The majority of the clinical problems
      were related to the inability capsule to reach the colon during the recording
      time. Capsule endoscopy provides a well-tolerated, safe and effective tool to
      investigate the gastrointestinal diseases, especially some small bowel diseases.

PMID- 18346321
TI  - [A study on the difference between International Diabetes Federation worldwide
      definition and Adult Treatment Panel III in diagnosing metabolic syndrome].
AB  - OBJECTIVE: To study the difference between the metabolic syndrome (MS) diagnosis
      made with International Diabetes Federation (IDF) worldwide definition and the
      Adult Treatment Panel III (ATPIII) of National Cholesterol Education Program
      (NCEP). METHODS: Cross-sectional study and descriptive study were used. RESULTS:
      There were 1328 MS patients diagnosed with IDF and 1527 MS patients diagnosed
      with ATPIII. There were 199 MS patients diagnosed with ATPIII but not with IDF
      and these MS patients all had 3 - 4 risk factors. According to the abnormality of
      glucose, blood pressure and lipid regulation stated in ATPIII criteria, 759 more
      patients were diagnosed as MS than with IDF criteria. CONCLUSIONS: MS diagnosed
      with ATPIII criteria is more objective than with IDF criteria and ATPIII criteria
      has more space for further theoretical study.

PMID- 18346322
TI  - [Associations between the plasma inflammatory markers and plaque morphologies of
      coronary artery lesions].
AB  - OBJECTIVE: To evaluate the vulnerability of coronary artery plaque with coronary
      angiography (CAG), intravascular ultrasound (IVUS) and the levels of plasma
      inflammatory markers. METHODS: 58 consecutive patients with lesion of a single
      blood vessel demonstrated successfully by CAG were randomly divided into 3 groups
      based on the angiographic morphology of the the lesions: type I lesion group (n =
      16), type II lesion group (n = 25), type III lesion group (n = 17). Meantime, a
      control group of stable angina (n = 17) was established. A subgroup of 28
      patients (including 18 acute coronary syndrome (ACS) patients and 10 stable
      angina control patients) who underwent IVUS study were analyzed. Then the plasma
      levels of high sensitivity CRP (hs-CRP), matrix metalloproteinase (MMP, including
      MMP-2 and MMP-9), CD(40) ligand (CD(40)L) and pregnancy associated plasma protein
      A (PAPP-A) were measured with ELISA. Analyses were performed by statistical
      package SPSS 11.0. RESULTS: The plasma levels of MMP-2, MMP-9 and PAPP-A in type
      II lesion group were significantly higher than the other groups (P < 0.05, 0.05,
      0.001, respectively). In type II lesion group, linear correlation analysis
      manifested significantly positive correlation between levels of hs-CRP and MMP-2
      (r = 0.508); MMP-2 and MMP-9, CD(40)L, PAPP-A (r = 0.647, 0.704, 0.751,
      respectively); MMP-9 and CD(40)L, PAPP-A (r = 0.491, 0.639, respectively);
      CD(40)L and PAPP-A (r = 0.896). IVUS subgroup analysis showed that the area of
      plaques and plaques burden in culprit lesion, the incidence of high-risk plaques,
      remodeling index (RI) and positive remodeling percentage in ACS patients were
      significantly greater than those in the control group (P = 0.000, 0.037, 0.028,
      0.015, 0.040, respectively). Compared with the control group, the plasma levels
      of hs-CRP, MMP-2, MMP-9 and PAPP-A were markedly elevated (P = 0.033, 0.000,
      0.000, 0.027, respectively). CONCLUSIONS: CAG and IVUS combined with the study on
      plasma levels of inflammation mediators were helpful in judging the vulnerability
      of coronary artery plaques.

PMID- 18346323
TI  - [A multicenter prospective cohort study on risk factors for hospital-acquired
      pneumonia in the elderly].
AB  - OBJECTIVE: To investigate the incidence and the risk factors for hospital
      acquired pneumonia (HAP) in the elderly in Shanghai. METHODS: This was a
      multicenter prospective clinical cohort study. A total of 5299 patients more than
      65 years old, admitted into 31 secondary or tertiary hospitals in Shanghai, were
      enrolled. Measurements of the demographic and potential risk factors reflecting
      illness severity, nutrition, drug exposure, surgery and ventilation were
      performed. Pneumonia was classified by the definition of Chinese Medical
      Association. Risk factors were analyzed by univariate Pearson Chi-squared test
      and multivariable logistic regression analysis with backward (Likelihood ratio).
      RESULTS: Of the enrolled patients, 2805 male and 2494 female, 255 (4.81%)
      developed hospital-acquired pneumonia. The incidence was 46.75/1000
      hospitalizations. Among them 38 died; and the rough mortality was 14.90%. The
      incidence of HAP was higher in ICU (21.43%), hematology (12.17%), chest surgery
      (11.41%), and respiratory medicine (7.92%) departments. The mean of acute
      physiology and chronic health evaluation (APACHE II) score was 8.3 +/- 3.4 (5 -
      31). Multivariable logistic regression analysis with backward (Wald) method found
      that admission into secondary hospitals, admission into ICU, history of chronic
      obstructive pulmonary disease > or = 10 years, immunosuppression, administration
      of antibiotics, insertion of nasogastric tube, mechanical ventilation,
      administration of H-2 antagonists or antacid and < or = 7 d, central nervous
      system diseases, depressed level of consciousness, supine position, albumin < 35
      g/L were independent risk factors of HAP in the elderly. CONCLUSION: Hospital
      acquired pneumonia in the elderly was the usual type of nosocomial infections.
      The risk factors identified from this study may prove useful to target future
      clinical interventions to prevent HAP in the elderly.

PMID- 18346324
TI  - [The application of Montreal cognitive assessment in urban Chinese residents of
      Beijing].
AB  - OBJECTIVE: To study the distribution of Montreal cognitive assessment (MoCA)
      scores in terms of age and educational level in Chinese residents aged 50 years
      and over and to offer a benchmark for a cutoff score. METHODS: A total of 281
      residents aged 50 years or older was drawn randomly in the urban areas of
      Beijing, including 215 healthy elderly controls (NC) and 66 patients meeting the
      clinical criteria of mild cognitive impairment (MCI). The final scores for MoCA
      were given in the form of mean percentage distributions specific for age, sex and
      educational level so as to compare the validity of MMSE mini-mental state
      examination and MoCA in detecting MCI. By a fitting multiple regression model the
      influence of the factors on MMSE and MoCA was assessed. RESULTS: Using a cutoff
      score of 26, MMSE had a sensitivity of 24.2% to detect MCI, whereas MoCA detected
      92.4% of the MCI subjects. We found a bivariate correlation between MoCA scores
      and both the factors of age and educational level (P < 0.001). CONCLUSIONS: MoCA
      is a brief cognitive screening tool with high sensitivity and specificity for
      detecting MCI as currently conceptualized in patients performing normally on
      MMSE. Our adjustment in the cutoff scores would improve the detection of MCI and
      Alzheimer's disease by reducing the number of false negatives. MoCA scores should
      be used to identify current cognitive difficulties but not to make formal
      diagnoses.

PMID- 18346325
TI  - [A clinical analysis of severe cyclosporine A-related neurotoxicity after
      allogenic hematopoietic stem cell transplantation].
AB  - OBJECTIVE: To investigate the morbidity, clinical manifestations, and imageology
      characteristics, and the influencing factors of severe cyclosporine A (CsA)
      related neurotoxicity (SNCT) in the patients after allogenic hematopoietic stem
      cell transplantation (allo-HSCT). METHODS: Finding of SNCT was carried out in 164
      allo-HSCT recipients from January 2003 to June 2006. Clinical characteristics
      were analysed, including precursory symptoms and clinical manifestations.
      Associations between the onset of SNCT with blood CsA levels, age, transplant
      types, human leucocyte antigen (HLA) matching, conditioning regimens, antihuman
      thymocyte globulin (ATG) used in the prevention and treatment for graft-versus
      host disease (GVHD) and intravenous corticosteroid used for acute GVHD were
      analyzed. Statistical analysis was performed with Binary Logistic Regression
      using SPSS/PC version 11.0. RESULTS: Thirteen patients (7.93%) were identified to
      have SNCT, including seizures (n = 8, 4.88%), paralysis (n = 6, 3.66%), coma (n =
      2, 1.22%), cerebellar ataxia (n = 3, 1.83%) and chondroid encephalomyopathy (n =
      1, 0.61%). All the patients had precursory symptoms prior SNCT including headache
      (n = 8), agitation (n = 4) and hypertension (n = 6). Magnetic resonance imaging
      (MRI) performed in twelve patients after SNCT showed that eleven patients had
      signal abnormalities in cerebral cortex and cerebral white matter. Six patients
      examined with computerized tomography (CT) had no abnormal findings. After
      extenuation or withdrawal of CsA, ten patients had complete recovery, two had
      partial recovery and one died of SNCT. Simple effect analysis of Binary Logistic
      Regression showed that the associations between the onset of SNCT with blood CsA
      levels, transplant types, HLA matching, ATG used in the prevention and treatment
      for GVHD and intravenous corticosteroid used for acute GVHD were of statistical
      significance. The multiple effect analysis of Binary Logistic Regression showed
      that the associations of the onset of SNCT with blood CsA levels and ATG used had
      statistical significance and the odds ratio (OR) was 1.007 (P = 0.006) and 6.727
      (P = 0.030), respectively. CONCLUSIONS: 91.67% of the allo-HSCT recipients with
      SNCT have MRI abnormalities. High blood CsA levels and the use of ATG can elevate
      the risk of the occurrence of SNCT.

PMID- 18346348
TI  - [Updates on atherogenesis: the stem/progenitor cells hypothesis].

PMID- 18346349
TI  - [Clinicopathologic analysis of dilated heart in cardiac transplant recipients].
AB  - OBJECTIVE: To study the pathologic features of dilated heart in cardiac
      transplant recipients, with clinicoradiologic correlation. METHODS: Sixty
      recipient hearts from cardiac transplantation performed in Fuwai Hospital were
      analyzed by gross examination, histologic observation and electron microscopy.
      Clinicoradiologic correlation was available in 40 cases. RESULTS: Amongst the 40
      cases of dilated heart, 52.5% (21/40) were due to dilated cardiomyopathy, 22.5%
      (9/40) due to arrhythmogenic right ventricular cardiomyopathy, 15.0% (6/40) due
      to ischemic cardiomyopathy, and the remaining 10.0% (4/40) due to miscellaneous
      causes, including local noncompaction of ventricular myocardium, giant cell
      myocarditis, alcoholic cardiomyopathy and hypertensive cardiomyopathy. The
      discrepancy rate between clinical and pathologic diagnosis was 37.5% (15/40). The
      erroneous categories included arrhythmogenic right ventricular cardiomyopathy (7
      cases), ischemic cardiomyopathy (5 cases), and giant cell myocarditis (1 case),
      which were all mistaken clinically as dilated cardiomyopathy. While ischemic
      cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, noncompaction of
      ventricular myocardium and giant cell myocarditis have distinctive pathologic
      features, the diagnosis of alcoholic and hypertensive cardiomyopathies required
      clinicopathologic correlation. Dilated cardiomyopathy due to viral myocarditis
      was not identified in the cases studied. CONCLUSION: Pathologic examination is
      essential in analysis of transplant recipient heart and helps to rectify clinical
      diagnostic discrepancy.

PMID- 18346350
TI  - [Pathologic study of diabetic cardiomyopathy].
AB  - OBJECTIVE: To study the histopathologic features, differential diagnosis and
      pathogenesis of diabetic cardiomyopathy. METHODS: The clinicopathologic features
      of 40 autopsy cases of diabetes mellitus were studied. The hearts from another 40
      cases of non-diabetic elderly deceased were used for comparison. RESULTS: In the
      40 cases of diabetes studied, 36 cases (90.0%) showed microscopic myocardial cell
      death. Focal interstitial fibrosis was observed in 37 cases (92.5%). On the other
      hand, similar myocardial cell death and patchy interstitial fibrosis was seen in
      8 cases (20.0%) and 9 cases (22.5%) of non-diabetic hearts, respectively. The
      difference between the two groups was statistically significant (P < 0.01). The
      mural thickness of intramyocardial blood vessels was significantly increased in
      diabetic group (20.6 microm +/- 4.2 microm) than in non-diabetic group (7.2
      microm +/- 5.2 microm), P < 0.01.The myocardial changes in diabetic group however
      were similar to those in non-diabetic group with systemic hypertension.
      CONCLUSIONS: Pathologic diagnosis of diabetic cardiomyopathy relies on detailed
      histologic examination of heart tissue and clinical correlation of a long history
      of diabetes mellitus. Exclusion of other possible etiologies is also essential.
      The myocardial cell death observed may be due to the ischemic effect induced by
      diabetic microangiopathy in cardiac muscle.

PMID- 18346351
TI  - [Morphologic features of sudden cardiac death in Yunnan province, with emphasis
      on myocarditis].
AB  - OBJECTIVES: To study the pathologic feature of sudden cardiac death in Yunnan
      province and to investigate the role of myocarditis. METHODS: During the period
      from 1991 to 2006, there were 29 cases of sudden cardiac death with autopsy
      performed. Fourteen of these cases were diagnosed to have myocarditis based on
      Dallas criteria and World Heart Federation's consensus. The clinical and
      pathologic findings were reviewed. The cardiac conduction system was examined in
      details by serial sectioning in 3 cases. RESULTS: Fourteen cases suffered with
      myocarditis, which accounted for 48% of all cases of sudden cardiac death
      studied. The age of the deceased ranged from 8 to 68 years (mean = 30 years),
      with male-to-female ratio equaled to 9:5. Lymphocytic myocarditis and neutrophil
      myocarditis were the two major types, affecting 11 and 3 cases, respectively. The
      inflammatory infiltrates were often patchy rather than diffuse. The inflammatory
      foci were detected only in 8% to 42% (average = 20%) of the paraffin sections of
      the heart tissue. These lesions were usually located in the lateral wall of left
      ventricle and occasionally in interventricular septum and right ventricular wall.
      Myocardial injury was mild in most cases while patchy myocytolysis or coagulation
      necrosis was observed only in a few cases. Most of the lesions were relatively
      new and histologic evidence of myocardial repairing sometimes coexisted.
      Pericarditis and subacute endocarditis were also identified in 4 and 1 cases,
      respectively. Atrioventricular node was involved by myocarditis in 1 of the 3
      cases examined for cardiac conduction system. Two cases showed gross evidence of
      cardiac dilatation (either left ventricle or biventricular). Respiratory tract
      and pulmonary infection was present in 5 cases. CONCLUSIONS: Myocarditis
      represents one of the major pathologic changes of sudden cardiac death occurring
      in Yunnan province. The inflammation is usually focal. Further studies are
      required for delineation of possible etiologies which may include virus, bacteria
      or exogenous toxin.

PMID- 18346352
TI  - [Role of HPV DNA detection and p16(INK4A) protein expression in diagnosis of
      endocervical adenocarcinoma].
AB  - OBJECTIVES: To evaluate the significance of p16(INK4A) protein expression and
      positivity for HPV DNA in distinguishing between endocervical and endometrial
      adenocarcinoma. METHODS: Expression of p16(INK4A) protein in 30 cases of
      endocervical adenocarcinoma and 10 cases of endometrial adenocarcinoma was
      assessed by immunohistochemistry. In-situ hybridization for human papillomavirus
      (HPV) DNA was also performed in 20 cases of endocervical adenocarcinoma and 10
      cases of endometrial adenocarcinoma. RESULTS: The positive rate for p16(INK4A) in
      endocervical adenocarcinoma was 70% (21/30), as compared with 30% (3/10) in
      endometrial adenocarcinoma. The tumor cells in endocervical adenocarcinoma showed
      diffuse and strong expression of p16(INK4A) protein with both cytoplasmic and
      nuclear staining. In contrast, the endometrial adenocarcinoma cells showed patchy
      and weak expression of p16(INK4A). On the other hand, HPV DNA (type 16 or 18) was
      detected by in-situ hybridization in 9 (45%) of the 20 cases of endocervical
      adenocarcinoma and none of the 10 cases of endometrial adenocarcinoma.
      CONCLUSIONS: The expression of p16(INK4A) protein is significantly higher in
      endocervical adenocarcinoma than in endometrial adenocarcinoma. This expression
      pattern can serve as a useful immunohistochemical marker in the differential
      diagnosis. p16(INK4A) protein immunohistochemistry appears to be more sensitive
      than HPV DNA testing in distinguishing between endocervical and endometrial
      adenocarcinoma, especially in biopsy or curettage specimens.

PMID- 18346353
TI  - [Identification of metastasis-associated proteins of ovarian cancer by
      proteomics].
AB  - OBJECTIVE: To investigate the differenal protein expression profiles of ovarian
      tumor cell lines with distinct metastatic abilities. METHODS: The ovarian cancer
      cell line HO8910 and HO8910pm, derived from same parental cells but exhibited
      different metastatic ability, were investigated by two-dimensional gel
      electrophoresis (2-DE)-MALDI-TOF-MS proteomic approach. RESULTS: Thirty-nine
      proteins were detected by 2-DE to have expression disparity levels over 2 folds
      between two cell lines. Eighteen of them were identified by MALDI-TOF-MS. The
      proteins are involved in apoptosis, extra cellular matrix (ECM), cytoskeleton,
      growth factor, glycolysis, protein metabolism and immune system. CONCLUSION: The
      data are valuable for the identification of differentially expressed proteins
      involved in the biological behavior of human ovarian cancer.

PMID- 18346354
TI  - [Abnormal expression of bcl-10 protein in extranodal marginal zone B cell
      lymphoma of mucosa-associated lymphoid tissue lymphoma type].
AB  - OBJECTIVE: To evaluate the diagnostic role of nuclear expression of bcl-10
      protein in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid
      tissue (MALT) type. METHODS: One hundred and forty cases of MALT lymphoma were
      collected from Cancer Hospital of Fudan University (including 38 cases from
      stomach, 35 cases from ocular adnexa, 16 cases from intestine, 15 cases from
      skin, 15 cases from salivary gland, 14 cases from lung, 3 cases from thyroid and
      4 cases from other sites). Ten cases of reactive follicular hyperplasia of
      tonsil, 5 cases of reactive lymphoid hyperplasia of orbit and 143 cases of non
      Hodgkin's lymphoma other than MALT lymphoma (including 20 cases of NK/T cell
      lymphoma, 20 cases of follicular lymphomas, 20 cases of anaplastic large cell
      lymphomas, 20 cases of nodal diffuse large cell B-cell lymphoma (DLBCL), 10 cases
      of gastric diffuse large B-cell lymphoma, 13 cases of nodal marginal zone B-cell
      lymphoma, 12 cases of mantle cell lymphoma, 11 cases of splenic marginal zone B
      cell lymphoma, 6 cases of angioimmunoblastic T-cell lymphoma, 6 cases of
      peripheral T-cell lymphoma, not otherwise specified, 3 cases of small lymphocytic
      lymphoma, 1 case of lymphoplasmacytic lymphoma and 1 case of plasmacytoma were
      used as controls. Immunohistochemical study for bcl-10, as well as dual staining
      with CD20, was performed by EnVision method in paraffin sections. RESULTS: In
      reactive follicular hyperplasia of tonsil, bcl-10 was moderately or strongly
      expressed in the cytoplasm of germinal center B cells, while the mantle cells
      were negative and the marginal zone cells and paracortical T cells showed weak
      staining. In the 5 cases of reactive lymphoid hyperplasia of orbit, 2 were bcl-10
      negative and the remaining 3 expressed bcl-10 in the cytoplasm of germinal center
      B cells. As for non-MALT lymphomas, 3 gastric DLBCL showed nuclear expression.
      The remaining cases showed variable cytoplasmic staining. In some cases of
      lymphoma, bcl-10 was expressed in tumor cells but not in reactive lymphoid cells.
      On the other hand, 92.1% (129/140) of MALT lymphoma were bcl-10 positive. Among
      those cases, 54.3% (76/140) showed cytoplasmic positivity and 37.9% (53/140)
      showed nuclear positivity. The nuclear positivity rate of bcl-10 in different
      anatomic sites was different. The staining was most intense in MALT lymphoma of
      ocular adnexa. Dual staining with CD20 showed that the bcl-10-positive cells were
      also CD20-positive, though the number of bcl-10-positive cells were less than
      that of CD20-positive cells. CONCLUSIONS: Bcl-10 expression in lymphoid
      hyperplasia is a universal phenomenon. Cytoplasmic expression of bcl-10 is seen
      in many different kinds of non-Hodgkin's lymphoma and reactive lymphoid
      conditions. In some cases of lymphoma, bcl-10 is expressed in tumor cells but not
      in reactive lymphoid cells, suggesting a possible role of abnormal bcl-10
      expression in tumorgenesis. Nuclear expression of bcl-10 is seen mainly in MALT
      lymphoma, especially when occurring in ocular adnexa and lung. This is in
      contrast to loss of bcl-10 expression in residual germinal center cells.

PMID- 18346355
TI  - [Filtrating smooth muscle progenitor cells from mouse bone marrow mesenchymal
      stem cells by recombinant Psm22alpha-EGFP-1].
AB  - OBJECTIVE: To identify and select smooth muscle progenitor cells from mouse bone
      marrow mesenchyme stem cell population and to characterize smooth muscle
      progenitor cells in peripheral blood. METHODS: Recombinant expression vector with
      the promoter of sm22alpha was constructed to have an enhancement type green
      fluorescent protein expression plasmid (EGFP-1). The construct was transfected
      into mouse bone marrow mesenchyme stem cells using Lipofectamine 2000.
      Morphological assessment was performed and the expressions of myocardin at
      protein and mRNA levels by fluorescence microscope and RT-PCR were evaluated at
      3, 5, 7, and 10 d targeting CD34 positive bone mesenchyme stem cells. RESULTS:
      The transfection efficiency of the positive control group was 70% +/- 1.5% (P >
      0.05). Expected green fluorescent proteins expressed at 3rd day. The numbers of
      green fluorescent cells in experimental groups increased with the time and
      reached the peak at the 7th day, and declined thereafter. The shapes of the green
      fluorescent cells were also different from each others. The positive ratios of
      green fluorescent cells at different time points: 3 d: 7% +/- 0.13%, 5 d: 10% +/-
      0.32%, 7 d: 20% +/- 0.26%, 10 d: 12% +/- 0.18%, P < 0.05. Myocardin mRNA
      expression roughly correlated with green fluorescent expressions. CD34 was
      expressed on the 5th day in transfected bone mesenchyme stem cells. The CD34
      positive ratio was 5.2% +/- 0.21% (P > 0.05). CONCLUSIONS: There are smooth
      muscle progenitor cells among mouse bone marrow mesenchyme stem cell population.
      Smooth muscle progenitor cells can be selected using a Psm22alpha-EGFP-1
      recombinant expression approach.

PMID- 18346356
TI  - [The influence of different microenvironments on melanoma invasiveness and
      microcirculation patterns].
AB  - OBJECTIVE: To investigate the influence of different microenvironments on tumor
      microcirculation patterns and invasive capability. METHODS: Melanoma B16 cells
      were injected into the peritoneal cavity and skeletal muscle of C57 mice
      synchronously. CK18 expression in melanoma was assessed to distinguish the
      malignant phenotype of tumors in the peritoneal cavity from that in the skeletal
      muscle. HIF-1alpha, MMP-2 and MMP-9 protein and mRNA expression were compared in
      the two microenvironments. Cells positive for each immunohistochemical stain and
      the vessels representative of each type of microcirculation pattern were
      evaluated in two microenvironments. RESULTS: CK18 and HIF-1alpha expression in
      melanoma were significantly higher in the skeletal muscle than in the peritoneal
      cavity (t = 8.142, t = 3.645, P < 0.05). Compared with the peritoneal cavity,
      melanoma cells in the skeletal muscle overexpressed MMP-2 and MMP-9 (t = 4.916, t
      = 7.782, P < 0.05). Real time-PCR results also showed that MMP-2 and MMP-9 mRNA
      levels in melanoma were higher in the skeletal muscle than in the peritoneal
      cavity (t = 36.814, t = 26.025, P < 0.05). Vasculogenic mimicry channels and
      endothelium-dependent vessels were the major microcirculation patterns in the
      skeletal muscle and in the peritoneal cavity respectively. CONCLUSIONS: Different
      microenvironments affect invasiveness and blood supply patterns of melanoma.
      Different microenvironment induced tumor cell secretion of more invasion-related
      proteins and affect invasiveness and blood supply patterns of melanoma.

PMID- 18346357
TI  - [Pathologic and clinical features of invasive micropapillary carcinoma of
      breast].

PMID- 18346358
TI  - [Expression and significance of Ser10 phosphorylated p27(kip1) and JAB1 protein
      in human hepatocellular carcinoma].

PMID- 18346359
TI  - [Clinical utility of OCT4 in diagnosis of germ cell tumor].

PMID- 18346360
TI  - [Updates on clinicopathologic researches of pilocytic astrocytoma].

PMID- 18346361
TI  - [Basal-like carcinoma of breast: one new subtype of breast neoplasms].

PMID- 18346362
TI  - [Application of double immunostaining in resin-embedded bone marrow biopsy
      specimens].

PMID- 18346363
TI  - [Diagnosis and differential diagnosis of uncommon malignant tumor cells in
      cervical cytology].

PMID- 18346364
TI  - [Cholesterol crystal embolism of toe: report of a case].

PMID- 18346365
TI  - [Littoral cell angioma of the spleen in a patient with chronic hepatitis B and
      hepatocellular carcinoma].

PMID- 18346366
TI  - [Leiomyosarcoma of breast with skin metastasis: report of a case].

PMID- 18346367
TI  - [Primary epithelioid sarcoma of the scalp: report of a case].

PMID- 18346368
TI  - [Insisting on health equity, promoting health system reform and medicine
      progress].

PMID- 18346369
TI  - [Functional magnetic resonance imaging-integrated neuronavigation and protection
      of brain function].
AB  - OBJECTIVE: To investigate the reliability and clinical value of functional
      magnetic resonance imaging (fMRI)-integrated neuronavigation in minimally
      invasive neurosurgery and protection of brain function. We demonstrate the
      correlation between the lesion-to-fMRI activation distance and occurrence of new
      postoperative deficit. METHODS: fMRI-integrated neuronavigation was used for
      minimally invasive neurosurgery in 20 patients with intracranial lesions located
      in or near eloquent brain areas. During standardized paradigms for hand, foot,
      and tongue movement, language and visual activation, echo-planar imaging T2 blood
      oxygen level dependent sequences were acquired by Siemens Medical Systems Trio
      3.0 T and processed with SPM2. Neuronavigation was performed with Stealth
      station. RESULTS: fMRI data was integrated into neuronavigation successfully in
      all cases, functional neuronavigation with integration of fMRI allowed easy and
      precise identification of the eloquent brain areas and lesions except for 1 case
      for brain shift because of tumor stroke just before the operation. The
      localization of the tumor was corrected by intraoperative ultrasonography. Gross
      total resection was achieved in 18 patients, 2 patients had a subtotal resection.
      Neurological deterioration was seen in 4 patients, tumors all located in eloquent
      brain areas, 2 patients were recovered in 3 months the morbidity was 10.0%. The
      distance of a lesion to fMRI activation was more than 10 mm in 14 cases. The
      functional maps were located in left Brodmann's 9, 46, 17, 18 and 19 areas in 11
      cases when the patients reading and understanding the Chinese words. CONCLUSIONS:
      Functional neuronavigation with integration of fMRI allows precise identification
      of the eloquent brain areas protects the brain function and decreases the
      morbidity especially for Chinese patients because of our special functional area
      of language. Our data suggest that the distance of a lesion to fMRI activation
      was more than 10 mm, complete resection can be achieved safely.

PMID- 18346370
TI  - [Preliminary study of protein expression profiling of PCOS on different state].
AB  - OBJECTIVE: To screen the serum protein expression profiles in patients having
      polycystic ovary syndrome (PCOS) with or without insulin resistance (IR) and
      search for discriminatory proteins. METHOD: Fasting serum samples of 30 PCOS
      patients with IR, 30 PCOS patients without IR, and 30 control individuals from
      Reproductive Center of Peking University Third Hospital were studied. RESULTS:
      There were 27 differential protein peaks between PCOS IR patients and controls,
      17 between PCOS non-IR patients and controls, and 19 between PCOS IR patients and
      non-IR patients. Marker proteins from differentially expressed proteins were
      screened out using support vector machine (SVM), and were used to establish three
      diagnostic models for PCOS IR, PCOS non-IR, and IR, respectively. CONCLUSIONS:
      There were significantly different serum proteomic patterns in different types of
      PCOS. Using Protein Chip combined with SVM, computer diagnostic models for PCOS
      with and without IR were set up quickly and efficiently. These discriminatory
      proteins may help us understand the proteomic changes in serum and find out
      potential biomarkers of PCOS and IR.

PMID- 18346371
TI  - [Study on changes of CT performance and pulmonary function in renal transplant
      recipients with pneumocystis pneumonia].
AB  - OBJECTIVE: To investigate dynamic changes of CT performance and pulmonary
      function in renal transplant recipients with pneumocystis pneumonia. METHODS: A
      retrospective analysis was made upon the clinic data of chest CT, arterial blood
      gas and pulmonary function in renal transplant recipients with pneumocystis
      pneumonia from 2002 to 2006 in the first affiliated hospital of Wenzhou Medical
      College. RESULTS: 16 cases were enrolled, followed by average age (36 +/- 11)
      years, mean duration after transplantation (4.3 +/- 2.1) months, mean course of
      disease (4.5 +/- 1.8) days. CT performance after admission revealed diffuse
      alveolar exudates and consolidation in all patients, and others still showed
      focal emphysema. With effective treatment, CT performance showed resolution of
      lung opacities completely until the second month, just little fiber remained. The
      pulmonary dysfunction showed apparent restrictive ventilatory abnormal and
      decreased DLco. Pulmonary dysfunction improved in the coming 3 - 4 weeks, and all
      dysfunction became complete resolution by the third month. CONCLUSIONS: The
      characteristic CT performance was focused on the alveolar, with exudates,
      consolidation and focal emphysema. The main pulmonary dysfunction showed
      restrictive ventilatory abnormality and decreased DLco. Under effective therapy,
      these abnormalities would improve significantly by the third month.

PMID- 18346372
TI  - [The detection rate of prostate cancer in different prostate-specific antigen
      (PSA) levels in Chinese men].
AB  - OBJECTIVE: To investigate the detection rate of prostate cancer in different PSA
      values and evaluate the importance of free PSA/total PSA in the diagnosis of
      prostate cancer in Chinese men. METHODS: We have analyzed 1244 patients who were
      submitted to needle biopsy since Jan 2000 to June 2005 in the Institute of
      Urology, Peking University. Systematic 12- or 13-core biopsies were taken
      transrectally under ultrasound (TRUS) guide for all of the patients. RESULTS: The
      prostate cancer detection rates in the tPSA ranges of < 4 ng/ml with positive
      DRE; 4 - 10 ng/ml with f/tPSA > 0.16; 4 - 10 ng/ml with f/tPSA < 0.16; 10.1 - 20
      ng/ml and > 20 ng/ml. The positive biopsy rates were 18.1% (13/72), 11.6%
      (10/86), 17.4% (45/258), 24.9% (110/442), 56.7% (219/386) respectively. The
      higher levels of the PSA, the higher percentage of high grade (Gleason score > or
      = 8) prostate cancer. In conclusion, patients with PSA > 10 ng/ml or positive
      digital rectal examination (DRE) were strongly recommended to biopsy for
      detecting prostate cancer because of high positive rate. For the patients with
      PSA 4 - 10 ng/ml, the free PSA (fPSA/t PSA < 0.16) will play an important role to
      improve cancer detection rate.

PMID- 18346373
TI  - [Comparative study for detecting micrometastases of lymph nodes in patients with
      lung cancer].
AB  - OBJECTIVE: To set up a new method to detect occult micrometastases of lymph nodes
      in patients with no-small-cell lung cancer (NSCLC). METHODS: We had detected 195
      lymph node samples taken from 25 patients with NSCLC during the operations. Each
      lymph node sample was divided into two same parts in size. The one half part of
      lymph node should be examined by conventional histopathologic examination and
      immunohistochemical (IHC) staining. All the remaining lymph node samples of each
      patient should be mixed together for the reverse transcriptase-polymerase chain
      reaction (RT-PCR) if they located in the same region. As long as the presence of
      metastatic tumor in one lymph node was found by H&E staining, all other lymph
      node samples in the same region should not be detected by IHC staining or RT-PCR
      techniques. RESULTS: Frozen tissue sections of 135 lymph nodes that were staged
      as free of metastases by conventional histopathologic examination were screened
      by IHC staining. 31 lymph nodes showed single cell or cells clusters. Of 39
      groups mixed regional lymph nodes which were diagnosed to be devoid of metastases
      by conventional histopathologic examination, 11 groups were found to have
      positive reactions to cytokeratin 19-mRNA by RT-PCR. There was a correlation
      between IHC staining and RT-PCR for detection of nodal micrometastases of NSCLC
      (U = 7.682, P = 0.0001). CONCLUSION: IHC staining analysis can facilitate the
      detection of occult micrometastases in lymph nodes of NSCLC, and its assessment
      of nodal micrometastases can provide a refinement of TNM stage for partial
      patients with stage I to II. RT-PCR has the same value as IHC staining in
      detection of lymph nodal micrometastases. RT-PCR technique can reduce expense of
      the detecting micrometastases in lymph nodes.

PMID- 18346374
TI  - [Evaluation of a self-defined classification of uterine submucous myomas for
      guiding transcervical hysteroscopic electric resection].
AB  - OBJECTIVE: To value a new presurgical classification system of submucous myomas
      for predicting the difficulty and the safety of hysteroscopic myomectomy.
      METHODS: The clinical data of 491 patients who underwent hysteroscopic resection
      of submucous myomas were analyzed. The myomas were classified according to the
      Classification of the European Society for Gynaecological Endoscopy (ESGE) and
      our group's new classification, which consists of five parameters. The
      possibility of total resection of submucous myoma, the operating time and the
      frequency of any complications were considered. RESULTS: The ESGE classification
      showed significant differences between the level 0 and level I or II (both P <
      0.01). Hysteroscopic myomectomy was considered incomplete in 9 patients with
      myomas. The numbers of complete surgeries of level II was significant lower
      compared to level 0 or level I (P < 0.01). Using our new classification, the
      differences of both operating times and the numbers of complete surgeries between
      group B and A was significant (P < 0.01). CONCLUSION: The new classification
      gives more clues as to the difficulties of hysteroscopic myomectomy than the
      standard ESGE classification. Although a larger number of patients need to be
      evaluated by this classification.

PMID- 18346375
TI  - [Isolated superior mesenteric artery dissection: case for non-operative
      management].
AB  - OBJECTIVE: To sum up the experience in diagnosis and treatment of isolated
      superior mesenteric artery (SMA) dissection and determine the best management for
      this disease. METHODS: We retrospectively reviewed clinical data of two patients
      with isolated SMA dissection admitted in the first hospital of China medical
      university from October to December 2006 and 69 cases reported in the literature.
      RESULTS: SMA dissection without aortic involvement is a rare event. Most
      diagnoses were established by CT and arteriography. Therapeutic option has not
      yet been established, however, conservative and interventional treatments have
      been reported more frequently. In our two cases, CT angiography allowed the rapid
      diagnoses. They were treated by conservative method and interventional stent
      separately, and have been followed-up for seven months. The managements were
      successful. CONCLUSION: Early diagnosis and management directly influence the
      prognosis. The strategy of management should be determined by symptoms, blood
      supply of SMA, peritonitis et al.

PMID- 18346376
TI  - [The diagnosis and treatment of pancreatic cavernous hemangioma].
AB  - OBJECTIVES: To research the clinical features of pancreatic cavernous hemangioma.
      METHODS: Retrospectively analyzed 3 pancreatic cavernous hemangioma cases treated
      in our hospital during the last 20 years, and reviewed correlative literature.
      RESULTS: The incidence of pancreatic cavernous hemangioma was very low. It
      occurred more often in woman. As the early symptoms were not obvious and the
      imaging study were not specific, the misdiagnosis rate was high. Usually, the
      diagnosis was confirmed by the pathological result. CONCLUSION: Pancreatic
      cavernous hemangioma is a rare benign tumor of the pancreas. It's difficult to
      diagnosis before surgery. Surgery is the best treatment with satisfactory
      results, and its prognosis is fairly good.

PMID- 18346377
TI  - [Effects of epimedium flavonoids on synapse related protein in brains of dementia
      transgenic mice].
AB  - OBJECTIVE: To investigate changes of synapse related protein, such as
      synaptophysin (SYP) and postsynaptic dense material 95 (PSD-95), in brains of 10
      months old transgenic mice, and the effects of Epimedium flavonoids (EF) on
      expression of SYP and PSD-95 in brain of 10 months old of APP transgenic mice.
      METHODS: The mice of drug treated group were administered intragastrically by EF
      (at low doses of 0.03 and high dose of 0.1 g.kg(-1).d(-1)) from 4 to 10 months
      old. The mice of normal group and negative transgene group were administered of
      distilled water by the same way. The expression of SYP in CA1, CA3, and dentate
      gyrus (DG) areas of hippocampus and cortex, and PSD-95 in hippocampus and cortex
      were detected by immunohistochemistry and Western blot respectively. RESULTS:
      Compared to negative transgenic mice, the expression of SYP in cortex was
      decreased by 51.3% (P < 0.01). The IOD value of SYP immuno-reactivity cell in
      CA1, CA3 and DG areas of hippocampus in 10 months old transgenic mice were
      significantly decreased (the suppression rates were 59.1%, 57.7% and 56.5% in
      CA1, CA3 and DG respectively, all P < 0.01). The expression of PSD-95 in cortex
      decreased by 36.4% (P < 0.01). The count of PSD-95 immuno-reactivity cell in CA1
      area of hippocampus decreased with the suppression rate of 18.5% (P < 0.05).
      After being administered intragastrically by EF for 6 months, the expression of
      SYP in cortex of EF low doses and high dose group mice increased by 40.0% (P <
      0.05) and 106.4% (P < 0.01) respectively in comparison with that of the control
      group. The IOD value of SYP immuno-reactivity cell in hippocampal CA1, CA3 and DG
      areas of EF low and high dose group mice were all significantly increased (all P
      < 0.01). The expression of PSD-95 in cortex of EF low and high dose group mice
      increased by 57.3% (P < 0.05) and 84.3% (P < 0.01) respectively when compare to
      the control group. The count of PSD-95 immuno-reactivity cell in CA1 area of
      hippocampus of mice in EF high dose group increased by 22.5% (P < 0.05).
      CONCLUSION: Epimedium flavonoids could protect the synaptic structure and
      function by promoting the expression of synaptophysin and postsynaptic dense
      material 95, which suggest that Epimedium Flavonoids may have a promising
      application prospect in improving the synaptic impairment of AD.

PMID- 18346378
TI  - [The experimental investigation of the invasion and growth of laryngeal cancer by
      matrix metalloproteinase-2 and matrix metalloproteinase-9 gene silence together].
AB  - OBJECTIVE: To investigate the inhibitive role of the invasion and growth of
      laryngeal cancer by lentivirus mediated Matrix Metalloproteinase-2 (MMP-2) and
      Matrix Metalloproteinase-2 (MMP-9) gene silence. METHODS: RNA interference (RNAi)
      technic was used. Recombinant lentivirus of small interference RNA targeting MMP
      2 and MMP-9 gene were transduced into Hep-2 cells, and Reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to test MMP-2 and MMP-9 expression in
      Hep-2 cells. The effect of the invasive capability in Hep-2 cells after MMP-2
      RNAi-lentivirus and MMP-9-RNAi-lentivirus transduction was observed by Boyden
      assay. In vivo experiment, the nude mouse model of laryngeal squamous carcinoma
      was established and MMP-2-RNAi-lentivirus and MMP-9-RNAi-lentivirus were
      intratumoral injected. Finally, the tumor inhibitive effect was observed and the
      Proliferating cell nuclear antigen (PCNA) expression in xenografts were examined
      to evaluate proliferation change of the Hep-2 cells. RESULTS: The recombinant
      lentivirus can transduce the target cells efficiently. RT-PCR showed the
      expression of MMP-2 and MMP-9 were negative. Boyden assay showed there were (14
      +/- 4) Hep-2 cells permeate artificial basement which was less than that (32 +/-
      6) in the control group. In vivo, the average tumor weight and volume in treated
      group were significantly lower than those in the control group (P < 0.01) and the
      tumor inhibitive rate was 46.59%. Immunohistochemistry showed PCNA index in
      treated group was obviously lower than that in control group (P < 0.01).
      CONCLUSION: The invasion, growth and proliferation of laryngeal cancer can be
      inhibited by lentivirus mediated MMP-2 and MMP-9 gene silence together.

PMID- 18346379
TI  - [Effects of injuries pulmonary arterial endothelial cell induced by endotoxin on
      proliferation of pulmonary artery smooth muscle cells and interference effect of
      bone morphogenetic protein-2].
AB  - OBJECTIVE: To investigate the effects of injuries pulmonary arterial endothelial
      cell induced by endotoxin on proliferation of pulmonary artery smooth muscle
      cells and interference effect of bone morphogenetic protein-2, and at the same
      time explore its possible mechanism. METHODS: Upper liquid of normal PAEC
      incubated by DMEM for 24 h without serum (EC-CMI) or that of PAEC incubated by
      the same DMEM and same period after incubating with endotoxin at concentration of
      1 microg/ml for 1 h (EM-CMII) were collected and preserved for PASMC incubating.
      Confluent monolayer PASMC of rats were incubated with EC-CMI (group I), EC-CMII
      (group II), EC-DMII + BMP-2 1 ng/ml (group III), EC-DMII + BMP-2 10 ng/ml (group
      IV) and EC-DMII + BMP-2 100 ng/ml (group V) for 24 h. The cultured cells were
      identified by phase-contrast microscope and immunofluorescent stain of SMC
      specific antigen. The proliferation of PASMC were evaluated by the BrdU assay.
      The cell cycle analysis including proliferation index (PI) and S-phase cell
      fraction (SPF) were performed by the flow cytometry. the DNA synthesis was
      detected by [methyl-(3)H]-thymidine incorporation; the expression of cyclinD1
      mRNA was elucidated by RT-PCR technology; the analysis of phosphorylated Smad1
      (pSmad1) and expression of cyclinD1 protein were detected by Western-blot
      experiment. RESULTS: Cells were confirmed as smooth muscle by their typical "hill
      valley" morphological features displayed under phase-contrast microscope and by
      immunofluorescent staining of smooth muscle, Compared with group I, there were a
      significant increase in proliferation rate, S-phase cell fraction (SPF), DNA
      synthesis in group II. Compared with group II, there were no significant changes
      in group III about that data. But the groups with 10 or 100 ng/ml (group IV and
      group V) of BMP-2 significantly attenuated proliferation rate, S-phase cell
      fraction (SPF), DNA synthesis and expression of cyclinD1 mRNA and protein
      compared with EC-CM2 alone (group II, P < 0.01). Phosphorylated Smad1 increased
      in group IV and group V compared with group II, (P < 0.01). CONCLUSION: The BMP-2
      could downregulate expression of cyclinD1 gene by smad signaling transconduction
      system, then depressed proliferation of PASMCs by EC-CM2 in vitro culture. And
      this effect is dependent in the concentration range of 1 - 100 ng/ml.

PMID- 18346380
TI  - [The establishment of a rat model of chronic pulmonary infection due to
      Pseudomonas aeruginosa].
AB  - OBJECTIVE: To establish a rat model of chronic pulmonary infection by inoculating
      two different Pseudomonas aeruginosa embedded in minute seaweed alginate beads
      made by an ejection set with an acuminata hole to Sprague-Dawley rats. To
      evaluate the animal model with bacteriology and pathology values. METHOD: (1) 300
      healthy, clean Sprague-Dawley rats were divided into 3 groups randomly: the wide
      type Pseudomonas aeruginosa group (PAO(1) group), the mutant type Pseudomonas
      aeruginosa group (PAO-JP2 group) and the control group. (2) Two different
      Pseudomonas aeruginosa were embedded in minute seaweed alginate beads by an
      ejection set with an acuminata hole. Then the beads were inoculated into the
      rats' lung through tracheal intubation. The bacteria numbers in lung and
      pathology scores were measured 3, 7, 14, 28 days after infection. RESULTS: (1)
      The bacteriology values: No bacterium were detected in the control group. PAO(1)
      and PAO-JP2 were detected from rats of PAO1 and PAO-JP2 infected groups
      respectively. Bacterial number was higher than 10(5) CFU/g 3, 7 days after
      infection (LgCFU/g): 3 d: PAO1 group: 19 +/- 6, PAO-JP2 group: 17 +/- 7; 7 d:
      PAO1 group: 13 +/- 4, PAO-JP2 group: 12 +/- 4) and higher than 10(3) CFU/g 14, 28
      days after infection (LgCFU/g: 14 d: PAO1 group: 11.3 +/- 2.8, PAO-JP2 group: 9.6
      +/- 3.3; 28 d: PAO1 group: 9.1 +/- 1.5, PAO-JP2 group: 4.2 +/- 3.0). (2) The
      pathological changes showed: 3, 7 days after infection, lung abscess, edema,
      consolidation, haemorrhage can be seen from lungs of both groups. And at optical
      microscopic, alginate-Pseudomonas aeruginosa caused a pronounced inflammatory
      reaction with polymorphonuclear cells surrounding a bead. Small microcolonies
      formed at the periphery of the bead were also seen. 14, 28 days after infection,
      the consolidation reduced gradually and lung atelectasis, fibrinous adhesions and
      granulomas became the major pathological changes, which is more significant in
      the PAO(1) group. CONCLUSION: The animal model of chronic pulmonary infection can
      be established by inoculating Pseudomonas aeruginosa embedded in minute seaweed
      alginate beads made by an ejection set with an acuminata hole to Sprague-Dawley
      rats.

PMID- 18346381
TI  - [Correlation of expression of RhoC with invasiveness of prostate cancer cell line
      PC-3M in vitro].
AB  - OBJECTIVE: To investigate the expression of RhoC in prostate cancer cells with
      different metastatic potential and the correlation with invasiveness. METHODS:
      Expression of RhoC mRNA and protein in human prostate cancer cell subclones PC-3M
      2B4 with non-metastatic potential and PC-3M-1E8 with highly metastatic potential
      was detected by RT-PCR and Western blot. Eukaryotic expression plasmids of RhoC
      were constructed and transfected into PC-3M-2B4. The biological effects were
      observed, including in vitro invasion by Boyden chamber assay, motility by would
      healing assay, alteration of microfilament network by the staining of TRTIC
      phalloidin, activities of matrix metalloproteinases (MMP) by gelatin zymography
      analysis and expression of p-Akt by Western blot assay. RESULTS: The expression
      levels of RhoC mRNA and protein varied in the two different metastatic subclones
      of human prostate cancer cell. RhoC was significantly upregulated in the highly
      metastatic subclones in comparison to the nonmetastatic counterpart (P < 0.01).
      As shown in Boyden chamber assay, the invasive capacity of transfected cells
      overexpressing RhoC was significantly promoted as reflected by more penetrating
      cells (125.21 +/- 10.43) than the antisense transcripts (46.22 +/- 8.12), the
      negative (53.77 +/- 8.56) and blank controls (57.68 +/- 7.25). Further study by
      would healing assay indicated that cells overexpressing RhoC were more motile in
      actin-based active movement (would healing ratio after 16 h of the sense
      transcripts, antisense transcripts, negative controls and blank controls was
      62.38 +/- 2.36, 29.47 +/- 1.86, 32.23 +/- 2.43, 31.88 +/- 2.67 respectively). The
      TRITC-phalloidin staining revealed less actin filament bundles and a fuzzy
      network of shorter filaments in the sense transcripts. In addition, MMP-2
      activity and p-Akt expression level were upregulated in the sense transcripts.
      CONCLUSION: RhoC overexpression could promote the invasive capacity of human
      prostate cancer cell in vitro and it's expression level correlated positively
      with the metastatic capacity of human prostate cancer cell, so RhoC may be a
      potential target in the development of a novel strategy for treating metastasis
      of prostate cancer.

PMID- 18346382
TI  - [Effect of p38 MAPK on elemene-induced cell cycle arrest in C6 glioblastoma
      cells].
AB  - OBJECTIVE: To observe the effect of elemene on cell cycle of rat C6 glioblastoma
      cells. METHODS: Cell cycle analysis and expression of p38 in C6 glioblastoma
      cells under elemene treatment were measured by flow cytometry and Western blot.
      Flow cytometry and MTT assay were used to examine cell cycle and cell
      proliferation while C6 glioblastoma cells were pretreated with p38 inhibitor and
      DN-p38 plasmids. RESULTS: The fraction of C6 in the G0/G1 phase increased 11%,
      6.95%, 19.57% respectively in the presence of 40, 60 and 80 microg/ml elemene.
      The level of phosphorylated p38 MAPK was greatly increased in a dose and time
      dependent manner. Inhibition of p38 MAPK activation with SB203580 and DN-p38
      blocked elemene-induced anti-proliferation effect. CONCLUSION: Elemene could
      induce G0/G1 cell cycle phase arrest of C6 glioblastoma cells through up
      regulation of phosphorylated p38.

PMID- 18346389
TI  - Nickel.

PMID- 18346390
TI  - Systemic contact dermatitis.
AB  - Systemic exposure to allergens resulting in a cutaneous eruption is known as
      systemic contact dermatitis (SCD). Once sensitization occurs, varying exposures
      to antigens via multiple routes (including transepidermal routes, intravenous or
      intramuscular routes, inhalation, and ingestion) can result in systemic flare.
      This article highlights the different categories of common contactants, metals,
      medications, and plants, exposure to which leads to SCD. A comprehensive approach
      that takes into account all possible routes of exposure is essential in
      diagnosing SCD and in helping patients successfully avoid their allergens.

PMID- 18346391
TI  - Detection of nickel sensitivity has increased in North American patch-test
      patients.
AB  - BACKGROUND: Nickel allergy has been studied by contact dermatitis groups around
      the world, and the frequency of nickel sensitivity has been reported to be
      decreasing in some populations. OBJECTIVE: To review the prevalence of nickel
      allergy as observed by the North American Contact Dermatitis Group from 1992 to
      2004. METHODS: The computer database of the North American Contact Dermatitis
      Group was used to examine the prevalence of nickel allergy over the study period
      and to analyze it by time, sex, and age. RESULTS: From 1992 to 2004, 25,626
      patients were patch-tested. The percentage of women tested was fairly constant
      (61.4-66.3%). A steady increase in nickel sensitivity was seen from 1992 to 2004.
      Subgroup analysis did not identify a population with declining nickel allergy.
      CONCLUSIONS: Nickel allergy continues to increase in younger and older men and
      women patch-tested in North America.

PMID- 18346392
TI  - Preservatives and skin sensitization quantitative risk assessment.
AB  - BACKGROUND: Preservatives are an unfortunately common cause of allergic contact
      dermatitis (ACD). Often, this is in association with exposure to cosmetics or
      medicaments. Recently, a quantitative risk assessment (QRA) approach to the
      quantitation of safe exposure levels for sensitizers has been promulgated as a
      more effective tool for the identification of acceptable levels of potential
      sensitizers in consumer products. OBJECTIVE: To assess this QRA approach, which
      facilitates the prediction of acceptable exposure levels to skin sensitizers in
      consumer products, levels that are normally below the threshold for the induction
      of skin sensitization. METHODS: Retrospective QRA analysis on four preservatives
      in five consumer product types. RESULTS: The analysis shows that functional
      levels of preservatives may be somewhat above an ideal exposure level for some
      product types, an outcome that is consistent with the clinical picture.
      CONCLUSION: QRA represents a new tool that in the future should be used in
      combination with the assessment of microbiologic protection needs of specific
      product types to limit the problem of preservative ACD.

PMID- 18346393
TI  - Prevention of nickel release with barrier coatings.
AB  - BACKGROUND: Allergic contact dermatitis from nickel is very common in the United
      States. A barrier coating to be used on personal items such as snaps or watches
      would be of great use in preventing the consequences of nickel allergy.
      OBJECTIVE: To evaluate various barrier coatings and their ability to yield a
      negative dimethylglyoxime (DMG) test result. METHODS: Four different barrier
      coatings were assessed prior to soaking in saline, after soaking in saline for 2
      days, and after soaking in saline for 7 days. RESULTS: Depending on the number of
      coatings and the time soaked in saline, the different barriers showed different
      efficacies in yielding a negative DMG test result. CONCLUSIONS: Nickel Guard and
      Beauty Secrets Hardener were most effective in yielding a negative DMG test
      result. Beauty Secrets Hardener was the more cost-effective choice.

PMID- 18346394
TI  - Allergic contact dermatitis from medical adhesive bandages in patients who report
      having a reaction to medical bandages.
AB  - BACKGROUND: Medical adhesive bandages are extensively used in both inpatient and
      outpatient medicine. However, few reports describing proven allergic contact
      dermatitis (ACD) from medical adhesive bandages exist in the literature. These
      reports do not adequately correspond to the frequency that patients report having
      an "allergy" to medical adhesive bandages. OBJECTIVE: To determine if there is a
      chemical present in medical adhesive bandages that causes ACD in people who
      identify themselves as having an "allergy" to medical adhesive bandages. METHODS:
      Twenty-six patients were enrolled and underwent patch testing with our standard
      trays (104 chemicals) and a customized adhesive tray (54 chemicals and 10 tapes
      and bandages in their whole form). RESULTS: We were able to identify an allergen
      in four patients that was related to their presumed adhesive allergy (Mastisol,
      neomycin/bacitracin [two different patients], and cortisone-10 cream,
      respectively). However, there were no positive allergic reactions to the tapes or
      bandages or any relevant allergic reactions to our customized adhesive tray.
      Eight (73%) of the 11 patients who had the bandage or tape left on for 7 days had
      an irritant reaction. CONCLUSION: We feel that the perceived reactions are not
      secondary to ACD but instead are due to an irritant contact dermatitis.

PMID- 18346395
TI  - Allergens in corticosteroid vehicles.
AB  - BACKGROUND: Whereas allergy to vehicle ingredients (ie, excipients and
      preservatives) in topical steroid vehicles is well recognized, there are no data
      regarding which vehicle ingredients are in common use or on which vehicles and
      active molecules are associated with which ingredients. OBJECTIVE: To produce
      descriptive data on the use of allergenic vehicle ingredients in prescription
      topical corticosteroids. METHODS: The package insert for every steroid in
      widespread use in the United States was obtained from the manufacturer and used
      to generate an ingredient list for the product. RESULTS: There are seven vehicle
      ingredients that are commonly used in topical corticosteroid vehicles that are
      well-known allergens: propylene glycol, sorbitan sesquioleate, formaldehyde
      releasing preservatives, parabens,
      methylchloroisothiazolinone/methylisothiazolinone, lanolin, and fragrance. Of 166
      topical corticosteroids, 128 (including all creams) had at least one of these
      vehicle ingredients. More generic products were free of allergens than were
      branded products. Solutions and ointments were the least allergenic vehicles. The
      most commonly present potential allergens were propylene glycol and sorbitan
      sesquioleate. CONCLUSIONS: Most prescription topical corticosteroids have the
      potential to cause allergic contact dermatitis owing to vehicle ingredients.
      Dermatologists should be aware of this possibility and should consider
      prescribing agents that do not contain potentially allergenic vehicle
      ingredients.

PMID- 18346396
TI  - Relevance of positive patch-test reactions to fragrance mix.
AB  - BACKGROUND: Fragrances are an important cause of allergic contact dermatitis. We
      presume that the traditional fragrance mix (FM) detects 70 to 80% of fragrance
      allergic patients. FM has an irritant potential. Weak positive reactions may have
      a greater chance of being irrelevant than strong reactions. OBJECTIVE: To improve
      the appraisal of FM patch-test reactions, we studied the relevance of reactions
      of different strength. We also studied the predictive value of the following on
      the relevance of the initial FM patch-test results: patch-test results of a
      repeated FM test; results of patch tests with balsam of Peru, colophony, and
      ingredients of the mix; and (history of) atopic dermatitis. METHODS: One hundred
      thirty-eight patients who had doubtful positive (?+) or positive (+ to +++)
      reactions were included in the study. We determined relevance by history taking,
      location and course of the dermatitis, and additional patch testing. Patients
      were retested with FM and with each ingredient separately. RESULTS: The relevance
      of reactions to FM increases with the strength of the reactions. Predictors of
      relevance are the results of retesting with FM, the results of tests with the
      ingredients, and a history and/or present symptoms of atopic dermatitis.
      CONCLUSION: Retesting with FM and its ingredients may add to the benefit of patch
      testing.

PMID- 18346397
TI  - Black-spot poison ivy.
AB  - In black-spot poison ivy dermatitis, a black lacquerlike substance forms on the
      skin when poison ivy resin is exposed to air. Although the Toxicodendron group of
      plants is estimated to be the most common cause of allergic contact dermatitis in
      the United States, black-spot poison ivy dermatitis is relatively rare.

PMID- 18346398
TI  - Type I allergy to insulin: case report and review of localized and systemic
      reactions to insulin.
AB  - Allergic reactions to insulin preparations are not uncommon. Although patients
      often present with skin symptoms, most articles on insulin allergy are published
      in endocrinology and allergy journals. The purpose of this report is to describe
      a case of localized type I allergy to insulin as well as provide a review of the
      classification of insulin allergy, methods of evaluation, and management options.

PMID- 18346400
TI  - Naftifine: a review.
AB  - BACKGROUND: Naftifine is a topical allylamine that is effective and safe in the
      management of superficial dermatomycoses. Naftifine is fungicidal in vitro
      against a broad spectrum of dermatophyte fungi and provides good activity against
      Candida and Aspergillus species. It is also effective against gram-negative and
      gram-positive bacteria. OBJECTIVE: To provide a review of the pharmacologic
      properties and clinical efficacy of topical naftifine preparations. METHODS: A
      review of the medical literature was performed using PubMed (1965-2006) using the
      search term "naftifine." All available English-language articles discussing the
      pharmacology and clinical use of naftifine were reviewed for the article.
      RESULTS: Naftifine causes interruption of fungal ergosterol synthesis and
      accumulation of squalene in fungal organisms. Naftifine also has demonstrated
      anti-inflammatory properties such as a reduction in superoxide production and a
      reduction in polymorphonuclear leukocyte chemotaxis/endothelial adhesion.
      Naftifine has shown good efficacy and safety for a variety of conditions and is a
      useful treatment that provides both antifungal action and relief of inflammatory
      signs and symptoms. Few adverse events have been noted with naftifine use, the
      most frequent being mild and transient burning, stinging, or itching in the
      application area. CONCLUSION: Naftifine remains a reliable multifunctional agent
      for a variety of superficial infections.

PMID- 18346401
TI  - Incidence and mortality data from cutaneous melanoma in Trentino: registry-based
      study.
AB  - BACKGROUND: The province of Trento has been the target of health campaigns for
      early diagnosis of cutaneous melanoma for 30 years. OBJECTIVE: To evaluate
      incidence and mortality data of skin melanoma in the province from January 1992
      to December 2001. METHODS: The study is based on the provincial skin cancer
      registry and the regional mortality registry. Standardized incidence and
      mortality rates were computed, and time trends were evaluated. Incidence rates
      were modeled using Poisson regression. RESULTS: Five hundred fifty-four melanomas
      were diagnosed (226 in males and 328 in females). No period effect was revealed.
      Incidence rates in females were about 1.24 times those in males. No significant
      trend in mortality rates was observed. CONCLUSION: We examined incidence and
      mortality data of cutaneous melanoma during a 10-year period and failed to find
      any significant trend. It seems we have reached a plateau after many years of
      continuous, intensive health campaigns.

PMID- 18346402
TI  - Endothelin-3 is produced by metastatic melanoma cells and promotes melanoma cell
      survival.
AB  - BACKGROUND: Endothelin-3 (ET-3) is an essential paracrine factor for the
      proliferation, migration, and survival of embryonic melanocytes during fetal
      development. Its expression is tightly regulated, being completely turned off in
      adult skin. OBJECTIVE: In this study, results are presented that demonstrate
      abnormal expression of ET-3 by metastatic melanoma cells in both tissue biopsies
      and cell culture. Further, in vitro experiments showed that metastatic melanoma
      cells have the capacity to respond to ET-3 stimulation by increasing survival.
      CONCLUSION: Therefore, an abnormal autocrine stimulation pathway involving ET-3
      is present in metastatic melanoma cells. Blocking this signal transduction
      pathway may prove useful for the treatment of metastatic melanoma.

PMID- 18346403
TI  - Dermatologic manifestations of underlying infectious disease among illicit
      injection-drug users.
AB  - BACKGROUND: Drug use patterns and serious bloodborne infections commonly have
      dermatologic manifestations among illicit injection-drug users (IDUs). OBJECTIVE:
      To assess how self-reported skin conditions of IDUs may correlate with underlying
      infectious diseases after adjustment for drug use patterns. METHODS: Prospective
      analysis of factors associated with self-reports of skin rashes, cellulitis, oral
      lesions, and lymphadenopathy obtained from 1,065 IDUs enrolled in a large cohort
      study. Variables potentially associated with each outcome were evaluated using
      multivariate generalized estimating equations. RESULTS: In multivariate analyses,
      drug use patterns were associated with cellulitis, whereas human immunodeficiency
      virus (HIV) infection and hepatitis C (HCV) were not. HCV infection was
      independently associated with skin rashes (odds ratio [OR] 1.85; 95% CI 1.17
      2.94). HIV infection was independently associated with lymphadenopathy (OR 2.00;
      95% CI 1.52-2.63), skin rash (OR 2.12; 95% CI 1.57-2.86), and oral lesions (OR
      14.95; 95% CI 9.41-23.76). CONCLUSIONS: Self-reports of IDUs, which could easily
      be obtained as part of a functional inquiry in a clinical setting, correlate with
      specific drug use patterns and underlying bloodborne infections.

PMID- 18346404
TI  - Side effects of short-term oral corticosteroids.
AB  - BACKGROUND: Physicians frequently prescribe short-term corticosteroids (CSs) to
      treat acute and self-limiting diseases. Standard texts and articles do not
      usually discuss the possible, although infrequent, risks of short-term CSs.
      OBJECTIVE: To demonstrate that side effects, although uncommon, can occur with
      short-term CSs and that these can occasionally be serious. METHODS: Medline peer
      review literature in English (1985-2006) was searched to identify the potential
      risks of CSs. Standard textbooks of dermatology, gastroenterology, ophthalmology,
      pharmacology, respirology, and rheumatology were reviewed. Because the results
      showed some factual discordance and a dearth of precise data, the results for
      each body system were reviewed with two relevant clinical specialists at North
      York General Hospital (with at least 20 years' experience). Further information
      was obtained from a questionnaire of 200 physicians in North York General
      Hospital and by feedback from an additional 100 physicians during a presentation
      of this material at the American Academy of Dermatology. RESULTS: Short-term CSs
      are generally safe, but there have been numerous reports of associated avascular
      necrosis and a few cases of fatal varicella-zoster in immunocompetent patients.
      Severe mood changes and psychotic reactions rarely occur unpredictably with short
      term CSs. These events are rare, and most treatments with short-term CSs are
      problem free. CONCLUSIONS: Problems are infrequent, but patients must be informed
      of all material risks and treatment options. Thorough chart documentation is
      required, and patient consent must be given. CS doses should be as low as
      possible, and CS courses should be as infrequent and as short as possible. The
      literature reviewed in this article clearly indicates that a short course of CS
      of 1 week, in the absence of specific contraindications, is unlikely to be
      harmful (psychotic or prepsychotic episodes possibly excepted).

PMID- 18346405
TI  - Cost comparisons of managing complex facial basal cell carcinoma: Canadian study.
AB  - BACKGROUND: Basal cell carcinoma (BCC) is the most common human malignancy and
      accounts for over 60,000 new cases of cancer in Canada annually. Although
      expensive to the health care system, no Canadian studies have reported the costs
      involved in management. This study calculated the costs of managing high-risk
      BCCs using radiotherapy (RT) and Mohs micrographic surgery (MMS). METHODS: Forty
      nine consecutive complex BCC cases presenting to a skin cancer referral center
      were collected prospectively. All were located on the head and neck and were
      either recurrent disease or located in "at risk" sites such as the eye, ear, lip,
      or nose. All patients underwent MMS. A radiation oncologist reviewed each case
      retrospectively. The costs of MMS were the actual costs of the procedure, with an
      additional amount added to account for the technical costs of the surgery. The
      costs of RT included physician fees and technical fees. A sensitivity analysis
      was performed using known recurrence rates from the medical literature. RESULTS:
      Five patients were excluded from the comparative analysis because radiation was
      not recommended (age < 50 years or radiation would overlap with a previous
      radiation field). The direct cost of treating a patient with a single BCC was
      $871 (range $630-1,159) using MMS and $3,625 (range $3,430-3,971) using RT. The
      costs were significantly higher for patients with multiple tumors with both
      modalities (p = .02 for both). The direct costs of a "5-year cure" were $952
      (range $644-1,647) for MMS and $3,758 (range $3,564-4,675) for RT. CONCLUSIONS:
      This study attempted to document the costs associated with two well-recognized
      and effective methods of treating complex BCC in Ontario. Subgroup analysis
      revealed independent associations between aggressive histology, larger size, and
      complexity of surgical closure with higher costs. Although we did notice a trend
      toward greater costs in patients with recurrent disease, in males, younger
      patients, and tumors present for > 1 year, these did not reach significance
      within our sample size. Despite the limitation that treatment costs may be center
      and provincially dependent, we hope this preliminary report will initiate further
      study into comparing Canadian costs of managing skin cancer.

PMID- 18346406
TI  - Primary cutaneous eosinophil-rich anaplastic large cell lymphoma: report of an
      unusual case and literature review.
AB  - BACKGROUND: Cutaneous, neutrophil-rich anaplastic large cell lymphoma (ALCL) is
      an uncommon variant of ALCL that may be confused with inflammatory dermatoses.
      OBJECTIVE AND METHODS: We describe an eosinophil-rich variant of ALCL occurring
      on the left ear without systemic involvement. The lesion had inflammatory
      characteristics, which led initially to a histological diagnosis of an
      inflammatory process. Two months later, a second biopsy diagnosed eosinophil-rich
      variant of ALCL. The patient underwent radiation therapy, but due to the
      extensive deformation and mutilation of the ear, the patient elected to have the
      ear amputated. We discuss the clinicopathological findings and the differential
      diagnosis CONCLUSIONS: To the best of our knowledge, the occurrence of a
      cutaneous, eosinophil-rich variant of ALCL has not been previously reported. It
      is important to alert pathologists to this variant of ALCL so that this
      possibility may be considered in the early differential diagnosis of inflammatory
      cutaneous conditions.

PMID- 18346407
TI  - Onycholysis associated with capecitabine in patients with breast cancer.
AB  - BACKGROUND: Onycholysis, which is separation of the nail plate from the nail bed
      at its distal and lateral attachments, can cause pain and impair function and is
      a well-known side effect of traditional chemotherapeutic agents. OBJECTIVES: We
      present two cases of onycholysis associated with capecitabine in women with
      advanced breast cancer, who were initially referred for evaluation of
      onychomycosis and review the literature on capecitabine. CONCLUSION: Owing to the
      increased frequency of use of capecitabine for different cancers, physicians
      should be aware of this side effect.

PMID- 18346408
TI  - [Prevalence and clinical characteristics of microalbuminuria in the Spanish
      hypertensive population].
AB  - BACKGROUND AND OBJECTIVE: The presence of microalbuminuria (MAB) in hypertension
      is now considered a sign of target organ damage. The aim of this study was to
      determine the prevalence of MAB in the Spanish hypertensive population and to
      correlate the degree of urinary albumin excretion (UAE) with the severity of
      blood pressure (BP) elevation and the presence of other cardiovascular risk
      factors. PATIENTS AND METHOD: Cross-sectional study of 4,952 hypertensive
      patients attended in primary care centres. UAE was determined in a fresh urine
      sample by calculating the ratio of albumin to creatinine excretion (mg/g).
      RESULTS: Median UAE was 13 mg/g (interquartile range, 4-29). The prevalence of
      MAB considered as a UAE between 30 and 300 mg/g was 21.4% with an additional 1.8%
      of patients having overt proteinuria (UAE > 300 mg/g). Compared with
      hypertensives without MAB, those who presented this feature exhibited
      significantly higher (p < 0,001) systolic and diastolic BP (146/85 vs 142/83
      mmHg). The prevalence of MAB was also significantly higher (p < 0.001) in
      patients with other cardiovascular risk factors, such as hypercholesterolemia,
      smoking or a family history of early cardiovascular disease, and in those
      exhibiting other signs of target organ damage, such as left ventricular
      hypertrophy or mild renal insufficiency. CONCLUSIONS: MAB is present in more than
      20% of the hypertensive Spanish population attended in primary care centres.
      There is a clear correlation between MAB and both BP elevation and the presence
      of other cardiovascular risk factors and signs of target organ damage.

PMID- 18346409
TI  - [Microalbuminuria-related cardiovascular risk in diabetic patients and
      hypertensive (non diabetic) population].
AB  - BACKGROUND AND OBJECTIVE: The MICREX Study has shown an high prevalence of
      microalbuminuria in Extremadura among diabetic patients and hypertensive
      population. It has been retrospectively evaluated the cardiovascular risk
      associated to microalbuminuria and/or diabetes mellitus. PATIENTS AND METHOD: A
      total of 902 patients older than 18 years were studied (mean age, 68.7 [11.0]
      years; 370 men and 532 women; 469 were diabetics and 433 non diabetic
      hypertensives). Microalbuminuria was measured in every patient using
      albumin/creatinin reactive stick in fasting first morning urine. Anthropometric
      measures and previous cardiovascular diseases were recorded. RESULTS: Odds ratio
      of cardiovascular disease for all patients with microalbuminuria was 1.91
      (confidence interval [CI] 95%, 1.31-2.78; p = 0.001), for diabetic group it was
      1.87 (CI 95%, 1.15-3.04; p = 0.01) and for non diabetic hypertensives 1.78 (CI
      95%, 0.98-3.30; p = 0.06). The risk associated to all patients with diabetes
      mellitus (versus non diabetic hypertensives) showed an odds ratio = 1.59 (CI 95%,
      1.19-2.14; p = 0.02). Hypertension in diabetic subjects rises odds ratio up to
      2.13 (CI 95%, 1.30-3.48; p = 0.002). When hypertensives diabetics were compared
      to non diabetic hypertensives odds ratio was 1.88 (CI 95%, 1.37-2.57; p <
      0.0001). CONCLUSIONS: In a retrospective view microalbuminuria and diabetes
      mellitus were positively related to a higher risk of cardiovascular disease.
      Microalbuminuria and/or hypertension in diabetic patients were also associated to
      higher cardiovascular risk.

PMID- 18346410
TI  - [Determinants of carotid subclinical atherosclerosis in patients with rheumatoid
      arthritis. A case-control study].
AB  - BACKGROUND AND OBJECTIVE: Rheumatoid arthritis (RA) is characterized by high
      cardiovascular (CV) mortality, which seems related to systemic inflammation. Our
      aim was to quantify carotid atherosclerosis in RA and its relationship with the
      disease. PATIENTS AND METHOD: 73 RA patients and the same number of sex and age
      matched controls were enrolled, without history of cardiovascular events. Carotid
      intima-media thickness (IMT) and plaques were measured by ultrasonography. Its
      relationship with risk factors (RF), rheumatic disease characteristics, and
      inflammatory markers were analysed. RESULTS: Controls showed higher body mass
      index (BMI) and dyslipidemia. There were no differences in other risk factors or
      IMT. Age (p = 0.001), sex (p = 0.02), BMI (p = 0.002), waist perimeter (p =
      0.001), and hypertension (p = 0.005) had a relationship with IMT. Among disease
      characteristics, only time elapsed since RA diagnosis was associated with IMT.
      CONCLUSIONS: There was not an increased carotid subclinical atherosclerosis in
      patients with RA, beyond the effects of classical RF.

PMID- 18346411
TI  - [Lipoatrophy semicircularis].

PMID- 18346412
TI  - [Advances in medical treatment of epilepsy].

PMID- 18346413
TI  - [Whipple's disease. Analysis of 6 cases].
AB  - BACKGROUND AND OBJECTIVE: Whipple's disease (WD) is an infrequent multisystemic
      process, with a bacterial etiology and with a marked variability in relation to
      its clinical manifestations. The diagnosis is established by histopathologic
      study or by polymerase chain reaction (PCR) test. Our objective was to analyze
      the clinical characteristics and evolution of these patients. PATIENTS AND
      METHOD: We have reviewed the patients diagnosed with WD in our hospital during
      the last 20 years (1987-2007). RESULTS: We describe 6 patients with WD (5 men and
      one woman), with a mean age of 47 years. Most patients presented articular
      symptoms (n = 5), in 3 cases with intermittent rheumatism. The mean period of
      time previous to diagnosis was 59 months. All patients developed a chronic
      diarrheic syndrome, constitutional syndrome and polyadenopathies at the time of
      diagnosis. Laboratory studies showed increased erythrocyte sedimentation rate and
      C-reactive protein values, ferropenic microcytic anemia and low serum levels of
      cholesterol. The clinical diagnosis was confirmed by pathologic study in 5
      patients, and by means of PCR study of spleen tissue in one patient. All patients
      were treated with cotrimoxazole for 2 years, with resolution of the symptoms.
      After a mean follow-up of 98 months, no recurrence of the symptoms has been
      observed in any case. CONCLUSIONS: Articular symptoms in the form of intermittent
      rheumatism are the most common form of presentation of WD. Diarrheic and
      constitutional syndrome, which are observed later in all patients, as well as the
      presence of adenopathies, oblige us to discard this process.

PMID- 18346414
TI  - [Introduction to the Plan Nacional de Investigacion, Desarrollo e Innovacion 2008
      2011: the strategic action on health].

PMID- 18346415
TI  - [Fecal incontinence and idiopathic chronic constipation].

PMID- 18346416
TI  - [Tracheobronchial granular cell tumors. A clinicopathologic study of 4 cases].

PMID- 18346417
TI  - [Evaluation and monitoring of requirements for sputum microscopic study in
      tuberculosis surveillance].

PMID- 18346418
TI  - [Commentary of the article: Contreras Blasco MA. Erosive or inflammatory
      osteoarthritis: the great unknown. Med Clin (Barc). 2007;129:262-6].

PMID- 18346419
TI  - [Beta-thalassemia major and pregnancy to term].

PMID- 18346420
TI  - [Diffuse gastric carcinoma associated with localized Menetrier's disease].

PMID- 18346421
TI  - [Water-bottle heart. Cardiac tamponade].

PMID- 18346422
TI  - [Role of topical calcineurin inhibitors in dermatology].

PMID- 18346423
TI  - [Pharmacokinetics of tacrolimus following topical application of tacrolimus
      ointment in adult and paediatric patients with atopic dermatitis].
AB  - BACKGROUND: Safety concerns related to systemic immunosuppressive therapy have
      raised questions regarding systemic exposure to topically applied tacrolimus.
      OBJECTIVE: To summarise all currently available information on the
      pharmacokinetics of tacrolimus ointment and to compare it with the
      pharmacokinetics of systemic use of tacrolimus. RESULTS: Low and highly variable
      systemic exposure has been shown in pharmacokinetic studies of tacrolimus
      ointment performed in patients (adults and children) with moderate to severe
      atopic dermatitis. Patients with larger treatment areas tended to have higher
      exposure to the drug, but there was no evidence of systemic accumulation.
      Overall, 96, 92 and 97% of the blood samples assayed contained tacrolimus
      concentrations below 1 ng/ml, and 23, 17 and 20% of samples were below 0.025
      ng/ml (the lower limit of quantification) in adults, children aged 6-12 and
      infants aged 3-24 months, respectively. CONCLUSION: Although tacrolimus applied
      topically is absorbed systemically, the overall exposure as measured by the area
      under the curve (AUC)0-24 is low and highly variable. The extent of systemic
      exposure is higher in patients with larger treatment areas, but even in patients
      with up to 75% of the body surface area treated, the systemic exposure is
      substantially lower than that measured in transplant patients. Systemic exposure
      to tacrolimus tends to decrease as the skin lesions heal and there is no evidence
      of systemic accumulation despite repeated applications of ointment. The
      tacrolimus ointment was efficacious and well-tolerated.

PMID- 18346424
TI  - [Atopic dermatitis and tacrolimus in adults].
AB  - Topical treatment with tacrolimus is more effective than the placebo and the low
      potency corticosteroids in the treatment of atopic dermatitis (AD) in both adults
      and children while it has a similar potency as some topical corticosteroids of
      medium potency. Since it was put on the market, more evidence has been
      accumulating to make our previous statements and it has been demonstrated to have
      greater effectivity than topical pimecrolimus and oral cyclosporine. It is a safe
      drug and its side effects are of little importance. Specifically no side effects
      have been demonstrated due to its systemic absorption nor has there been any
      increase in skin infections. The most frequent side effect is burning sensation
      or increased pruritus in the area where the product is applied. It is more
      frequent if the lesions treated are very acute and is generally transitory, not
      causing the treatment to be discontinued. Furthermore, with the current
      information, it cannot be associated to an increase of any type of neoplasms.

PMID- 18346425
TI  - [Topical tacrolimus in atopic dermatitis in children].
AB  - More than five years have passed since tacrolimus (Protopic) has been put on the
      market in Spain. This is sufficient time to reevaluate the successes and failures
      that this product has had after the great expectations created prior to the time
      when it was put on the market based on its extensive experimentation in clinical
      trials and very encouraging results. It is also time to reconsider the future of
      the indications and uses of tacrolimus, to reconsider our personal experiences
      with it and to offer answers to the new questions that have arisen after five
      years of using the product. Tacrolimus was sold for topical use in the treatment
      of atopic dermatitis. Since atopic dermatitis (AD) is a disease that affects
      children more frequently, tacrolimus is a product oriented directly toward use in
      children. This entails some added concerns. In this article, we review the most
      relevant findings that have arisen in the last five years in regards to the
      treatment of AD with tacrolimus in children.

PMID- 18346426
TI  - [Safety information for tacrolimus: present and future].
AB  - In this article there were regarded the most frequent side effects that appear in
      the patients who have been treated with topical tacrolimus, and the association
      between topical tacrolimus and the development of tumors is unfolded. The
      irritation in the site of application of the tacrolimus can manifiest as
      pruritus, sensation of burning and/or eritema located to the area of the
      application. It is the most frequent side effect, independently of the duration
      of the study. The cutaneous infections, especially the viral ones, tend to be
      more numerous in patients with atopic dermatitis that receive topic tacrolimus.
      After reviewing the medical literature one concludes that nowadays there doesn t
      exist scientific evidence of an increase of skin cancer, lymphomas or systemic
      immunosuppression in those patients that use or have used topical tacrolimus.
      Nevertheless, it is not possible to exclude the possibility that there appear
      cutaneous and/or systemic long-term side effects.

PMID- 18346427
TI  - [Tacrolimus in diseases other than atopic dermatitis].
AB  - Topical tacrolimus is an immunosuppressant that acts through the inhibition of
      calcineurin and thus of the T cells. This causes a decrease in the production of
      interleukins, the granulocyte colony stimulating factor, alpha interferon and
      tumor necrosis factor. Although the use of topical tacrolimus is only indicated
      for the treatment of moderate or severe atopic dermatitis, its immunosuppressant
      effect and fewer side effects regarding topical corticosteroids have lead to the
      increase of its use in other types of inflammatory skin diseases. The purpose of
      this article is to review the use of tacrolimus in this group of diseases other
      than atopic dermatitis, this use not being authorized within the data sheet of
      the drug.

PMID- 18346428
TI  - [On the progress of Actas Dermo-Sifiliograficas].

PMID- 18346429
TI  - [Present and future of biologic therapy in dermatology].

PMID- 18346430
TI  - [Tinea capitis].
AB  - Tinea capitis is a widespread scalp infection in children caused by
      dermatophytes. In fact, it is the most common cutaneous mycosis in children but
      is uncommon in adults. The disease has been major public health concern for
      decades. Some factors implicated in infection include poor personal hygiene,
      crowded living conditions, and low socioeconomic status. It can be caused by any
      pathogenic dermatophyte except for Epidermophyton floccosum and Trichophyton
      concentricum. Trichophyton rubrum, the most commonly isolated dermatophyte
      worldwide, is rarely the causative agent of this infection. Tinea capitis is a
      classic example of the changing geographic patterns of dermatophytosis. In
      developed countries, Trichophyton tonsurans is the most common causative agent,
      whereas in developing countries such as Mexico, the most common agent is
      Microsporum canis followed by Trichophyton tonsurans. The increasing incidence of
      tinea capitis warranted a review of the current literature and treatment
      strategies.

PMID- 18346431
TI  - [Practical management of hidradenitis suppurativa].
AB  - Hidradenitis suppurativa is a chronic inflammatory disease that usually affects
      areas of the skin with a high density of apocrine glands (axillae, groin,
      perianal and perineal regions, submammary area, etc). It usually appears in women
      during puberty. The etiology of the disease is unknown, although it is thought to
      be a primary defect of the hair follicle. When diagnosing hidradenitis
      suppurativa, a number of genetic and hormonal predisposing factors should be
      considered alongside other putative triggers, such as obesity, smoking, and tight
      clothing. Diagnosis is essentially clinical and it is important to bear in mind
      the possible complications associated with the disease, such as the development
      of tumors. Management of the disease includes general measures (antiseptic soaps,
      warm baths, etc), pharmacological therapy (topical, intralesional, and systemic),
      surgery (direct closure, second-intention healing, grafts, flaps, etc), and other
      measures (carbon dioxide laser, radiation therapy, etc). It is important that the
      disease be diagnosed and treated as soon as possible given the potential physical
      and psychological problems that it can generate.

PMID- 18346432
TI  - [Childhood dermatosis in a dermatology clinic of a general university hospital in
      Spain].
AB  - BACKGROUND AND OBJECTIVES: Pediatric dermatology is a relatively new subspecialty
      for which few epidemiological studies are available. We aimed to determine the
      work load associated with this subspecialty and the most common presenting
      complaints among pediatric patients in the general dermatology clinic of our
      hospital. METHODS: A descriptive study was performed based on hospital records to
      analyze patients aged 16 years or under seen in our department in 2005 and their
      diagnoses. RESULTS: Pediatric dermatology accounts for 12.1 % of the work load in
      our department (1,329/10,998 patients were <or= 16 years old). By disease groups,
      tumors and infections were the most common diagnoses and accounted for 55.4 % of
      all cases. A long way behind was eczema (15.0 %) and diseases affecting hair
      follicles, nails, and sweat and sebaceous glands (8.8 %). The most common
      individual diagnosis was melanocytic nevus (19.8 %), followed by viral warts
      (12.1 %), atopic dermatitis (8.9 %), molluscum contagiosum (8.4 %), and acne (7.0
      %). CONCLUSIONS: In most developed countries, atopic dermatitis is the most
      common dermatologic disease in children. In our study, however, melanocytic nevus
      was the most common presenting complaint, reflecting perhaps that there are more
      children in Spain with multiple nevi due to overexposure to sunlight or because
      of concern about melanoma among the population. Another possibility is that Spain
      has fewer cases of atopic dermatitis than more industrialized countries in
      northern Europe. Measures to avoid exposure to sunlight and use of sunscreen
      should be promoted during infancy. This could help slow the increase of melanoma
      in the adult population.

PMID- 18346433
TI  - [Sociodemographic characteristics of spanish skin cancer patients].
AB  - INTRODUCTION: Most epidemiological studies of skin cancer have been performed in
      countries with very different population and geographic characteristics to Spain.
      Investigation of this disease in the Spanish population would therefore be of
      interest. METHOD: Over a 12-month period, this prospective study recorded the
      types of skin cancer in consecutive patients who attended a dermatology clinic
      for the first time in health care area 3 of the health service of the Spanish
      autonomous community of Murcia. The demographic and social characteristics of
      these patients were determined. The results obtained were analyzed with the SPSS
      program, version 11.5, and compared with other studies conducted in other
      countries. RESULTS: Malignant tumors were the third most common presenting
      complaint (16.9 %) and the fourth most common secondary complaint (8 %). The
      patients with skin cancer were older (69.52 years; 95 % confidence interval [CI],
      67.82-71.21 years) than the other patients in the sample (34.52 years; 95 % CI,
      33.23-33.81 years), and there were more men (51.7 %) than women (48.3 %). These
      individuals had a low level of schooling, which varied according to the type of
      tumor, and most had outdoor jobs, with a significantly higher exposure to
      sunlight (3.35 h/d; 95 % CI, 3.08-3.62 h/d) than the other patients (2.72 h/d; 95
      % CI, 2.58-2.86 h/d). Furthermore, fewer malignant cutaneous tumors were found in
      patients with a higher phototype. The length of time since onset of the
      presenting complaints was shorter for skin cancer (11.37 months; 95 % CI, 7.47
      15.26 months) than for other skin diseases (25.83 months; 95 % CI, 22.87-28.80).
      Also, there were no seasonal peaks in consultations for skin cancer, and
      treatment was essentially based on surgery and cryotherapy. In addition, more of
      these patients had follow-up visits (84 %) than other dermatology patients (33
      %). CONCLUSIONS: Malignant or premalignant skin lesions are a common presenting
      skin complaint in the Mediterranean region, with differences in terms of
      attendance rates and predominant tumor type compared to other countries. This is
      probably due to the high sun exposure and predominance of skin phototype III.
      Similar studies for the whole of Spain would be of interest.

PMID- 18346434
TI  - [Analysis of the demand for dermatological care in the immigrant population
      served by hospital Miguel Servet in Saragossa, Spain].
AB  - INTRODUCTION: In recent years there has been an increase in the size of the
      immigrant population consulting dermatology services in Spain. The aim of this
      study was to describe the epidemiological characteristics of this sector of the
      population in the health care area served by Miguel Servet Hospital in Saragossa,
      Spain. MATERIAL AND METHODS: Data were collected on immigrant patients seen in
      the dermatology department of our hospital during 2004. Dermatological diagnoses
      were classified according to the International Classification of Diseases, Ninth
      Revision, Clinical Modification. Statistical analysis was undertaken using the
      SPSS statistical package, Access database management software, and Excel
      spreadsheets. RESULTS: A total of 706 patients were seen, corresponding to
      approximately 4 % of all first appointments, and more women were seen than men, a
      difference that was statistically significant. The mean age of the patients was
      31 years and there were no statistically significant differences in age between
      the sexes. In order of frequency, the most common countries of origin of the
      patients were Ecuador, Colombia, Romania, Morocco, Gambia, Guinea, and Senegal.
      The most common skin diseases in this population group were infectious diseases,
      in particular mycoses, followed by viral diseases and pyodermatitis, as well as
      sexually transmitted diseases. In all cases, the incidence of the disease was
      higher than in the Spanish population. CONCLUSIONS: An appropriate knowledge of
      dermatological diseases in this population group is necessary both to obtain
      correct diagnosis and to develop preventative measures for imported diseases.

PMID- 18346435
TI  - [Keratoderma palmoplantaris varians (striata et areata), a form of chronic
      idiopathic acrokeratosis described by Degos].
AB  - We report a case of a 15-year-old boy with hyperkeratotic lesions that were
      linear or striated on the palms and nummular on the soles. He was the only family
      member known to be affected, suggesting that the condition could be attributed to
      a de novo mutation or the recessive form of keratoderma palmoplantaris striata,
      described by Degos as chronic idiopathic acrokeratosis. The lesions did not
      improve with topical treatments (keratolytic agents, emollients, or
      corticosteroids) or oral retinoids. We observed that scratching of the affected
      areas was the main reason for deterioration of the lesions.

PMID- 18346436
TI  - [Waldenstrom macroglobulinemia associated with cutaneous lesions and type I
      cryoglobulinemia].
AB  - Waldenstrom macroglobulinemia is a blood dyscrasia characterized by monoclonal
      proliferation of B cells in the bone marrow, lymph nodes, and spleen. Patients
      with this disease show elevated serum levels and tissue deposition of monoclonal
      immunoglobulin (Ig) M produced by these aberrant cells. We present the case of a
      patient with Waldenstrom macroglobulinemia who suffered cutaneous lesions
      resulting from deposition of k light chains of IgM and clinical manifestations
      secondary to associated type I cryoglobulinemia. We discuss the different
      pathological cutaneous processes caused by IgM in Waldenstrom macroglobulinemia.

PMID- 18346437
TI  - [Perifollicular xanthomatosis as a key histological finding in Fox-Fordyce
      disease].
AB  - Fox-Fordyce disease is a rare skin condition characterized by the presence of
      multiple pruritic follicular papules in areas rich in apocrine glands, such as
      the axillae, mammary areolae, or genital regions. There is a high degree of
      variability in the histological findings seen in Fox-Fordyce disease. In addition
      to those described as typical of this entity, such as dilation of the
      infundibulum and hyperkeratosis and spongiosis of the infundibular epithelium,
      many other histological changes can be observed. We report the case of a 21-year
      old woman with Fox-Fordyce disease and highlight the importance of perifollicular
      xanthomatosis as a key histological finding in the diagnosis of the disease.

PMID- 18346438
TI  - [Symmetric palmar hyperkeratosis and esophageal carcinoma].

PMID- 18346439
TI  - [Vesicular eruption associated with conjunctival injection].

PMID- 18346440
TI  - [Circumscribed leprosy-like leukemia cutis].

PMID- 18346441
TI  - [Are moles dangerous?].

PMID- 18346442
TI  - [Inflammatory cutaneous metastasis as a first sign of recurrence of squamous cell
      carcinoma of the lung].

PMID- 18346443
TI  - [Compliance with topical treatment for bullous pemphigoid in patients with a high
      level of dependency for daily activities].

PMID- 18346444
TI  - [Acneiform eruption secondary to cetuximab with pseudomalignant histopathological
      changes].

PMID- 18346445
TI  - [Tunnelized preauricular transposition flap for reconstruction of anterior
      auricular defects].

PMID- 18346446
TI  - [Resolution of recalcitrant condyloma acuminata in a patient with human
      immunodeficiency virus treated with cidofovir].

PMID- 18346447
TI  - [Neonatal zosteriform herpes simplex].

PMID- 18346448
TI  - [A case of linear atrophoderma of Moulin].

PMID- 18346449
TI  - [A case of chronic graft vs host disease treated with photopheresis].

PMID- 18346451
TI  - Influence of herd structure and type of virus introduction on the spread of
      bovine viral diarrhoea virus (BVDV) within a dairy herd.
AB  - A herd is a population structured into groups not all equally in contact, which
      may influence within-herd spread of pathogens. Herd structure varies among cattle
      herds. However, published models of the spread of bovine viral diarrhoea virus
      (BVDV) assume no herd structure or a unique structure chosen as a representative.
      Our objective was to identify--for different index cases introduced into an
      initially BVDV--free dairy herd - risky (favourable) herd structures, which
      increased (decreased) BVDV spread and persistence compared to a reference
      structure. Classically, dairy herds are divided into calves, young heifers, bred
      heifers, lactating cows and dry cows. In the reference scenario, groups are all
      equally in contact. We evaluated the effect of isolating or merging groups. Three
      index cases were tested: an open persistently-infected (PI) heifer, an open
      transiently-infected heifer, an immune heifer carrying a PI foetus. Merging all
      groups and merging calves and lactating cows were risky scenarios. Isolating each
      group, isolating lactating cows from other groups, and merging calves and young
      heifers were favourable scenarios. In most structures, the most risky index cases
      were the following: first, the entry of a PI heifer; second, the birth of a PI
      calf; last, the entry of a transiently-infected heifer. Recommendations for dairy
      herds are to raise young animals together before breeding and to isolate
      lactating cows from others as much as possible. These recommendations will be
      less efficient if a PI adult enters into the herd.

PMID- 18346452
TI  - Detection of nonauthorized genetically modified organisms using differential
      quantitative polymerase chain reaction: application to 35S in maize.
AB  - Detection of nonauthorized genetically modified organisms (GMOs) has always
      presented an analytical challenge because the complete sequence data needed to
      detect them are generally unavailable although sequence similarity to known GMOs
      can be expected. A new approach, differential quantitative polymerase chain
      reaction (PCR), for detection of nonauthorized GMOs is presented here. This
      method is based on the presence of several common elements (e.g., promoter, genes
      of interest) in different GMOs. A statistical model was developed to study the
      difference between the number of molecules of such a common sequence and the
      number of molecules identifying the approved GMO (as determined by border
      fragment-based PCR) and the donor organism of the common sequence. When this
      difference differs statistically from zero, the presence of a nonauthorized GMO
      can be inferred. The interest and scope of such an approach were tested on a case
      study of different proportions of genetically modified maize events, with the
      P35S promoter as the Cauliflower Mosaic Virus common sequence. The presence of a
      nonauthorized GMO was successfully detected in the mixtures analyzed and in the
      presence of (donor organism of P35S promoter). This method could be easily
      transposed to other common GMO sequences and other species and is applicable to
      other detection areas such as microbiology.

PMID- 18346453
TI  - Role of ceramide in membrane protein organization investigated by combined AFM
      and FCS.
AB  - Ceramide-induced alterations in the lateral organization of membrane proteins can
      be involved in several biological contexts, ranging from apoptosis to viral
      infections. In order to investigate such alterations in a simple model, we used a
      combined approach of atomic force microscopy, scanning fluorescence correlation
      spectroscopy and confocal fluorescence imaging to study the partitioning of
      different membrane components in sphingomyelin/dioleoyl
      phosphatidylcholine/cholesterol/ceramide supported bilayers. Such model membranes
      exhibit coexistence of liquid-disordered, liquid-ordered (raft-like) and ceramide
      rich lipid phases. Our results show that components with poor affinity toward the
      liquid-ordered phase, such as several fluorescent lipid analogues or the synaptic
      protein Synaptobrevin 2, are excluded from ceramide-rich domains. Conversely, we
      show for the first time that the raft-associated protein placental alkaline
      phosphatase (GPI-PLAP) and the ganglioside GM1 are enriched in such domains,
      while exhibiting a strong decrease in lateral diffusion. Analogue modulation of
      the local concentration and dynamics of membrane proteins/receptors by ceramide
      can be of crucial importance for the biological functions of cell membranes.

PMID- 18346454
TI  - Novel Rath peptide for intracellular delivery of protein and nucleic acids.
AB  - In the present study, a novel cell penetrating peptide (CPP) named as Rath, has
      been identified from the avian infectious bursal disease virus. It has the
      potential to penetrate and translocate cargo molecules into cells independent of
      temperature. Additionally, it can deliver oligonucleotide in 30min and antibodies
      within an hour intracellular to chicken embryonic fibroblast primary cells. As an
      ideal delivery vehicle, it has the ability to protect the cargo molecules in the
      presence of serum, nucleases and has minimal or no cytotoxicity at even higher
      peptide concentrations studied. The biophysical characterizations showed that
      Rath has a dominant beta structure with a small alpha helix and has remarkable
      binding ability with protein and DNA. Thus, the characterization of unique Rath
      peptide to deliver protein or nucleic acid into the cells with non-covalent
      interaction could be used as an effective delivery method for various cell based
      assays.

PMID- 18346455
TI  - PACAP decides neuronal laminar fate via PKA signaling in the developing cerebral
      cortex.
AB  - Laminar formation in the developing cerebral cortex requires the precisely
      regulated generation of phenotype-specified neurons. To test the possible
      involvement of pituitary adenylate cyclase-activating polypeptide (PACAP) in this
      formation, we investigated the effects of PACAP administered into the
      telencephalic ventricular space of 13.5-day-old mouse embryos. PACAP partially
      inhibited the proliferation of cortical progenitors and altered the position and
      gene-expression profiles of newly generated neurons otherwise expected for layer
      IV to those of neurons for the deeper layers, V and VI, of the cerebral cortex.
      The former and latter effects were seen only when the parent progenitor cells
      were exposed to PACAP in the later and in earlier G1 phase, respectively; and
      these effects were suppressed by co-treatment with a protein kinase A (PKA)
      inhibitor. These observations suggest that PACAP participates in the processes
      forming the neuronal laminas in the developing cortex via the intracellular PKA
      pathway.

PMID- 18346456
TI  - Methylation of the DFNA5 increases risk of lymph node metastasis in human breast
      cancer.
AB  - The pathogenesis of breast cancer involves multiple genetic and epigenetic
      events. In this study, we report an epigenetic alteration of DFNA5 in human
      breast cancer. DFNA5 gene was silenced in breast cancer cell lines that were
      methylated in the DFNA5 promoter, and restored by treatment with the
      demethylating agent, 5-aza-dC, and gene knock-down of DFNA5 increased cellular
      invasiveness in vitro. The mRNA expression of DFNA5 in breast cancer tissues was
      down-regulated as compared to normal tissues. Moreover, the DFNA5 promoter was
      found to be methylated in primary tumor tissues with high frequency (53%, 18/34).
      Quantitative methylation-specific PCR of DFNA5 clearly discriminated primary
      breast cancer tissues from normal breast tissues (15.3%, 2/13). Moreover,
      methylation status of DFNA5 was correlated with lymph node metastasis in breast
      cancer patients. Our data implicate DFNA5 promoter methylation as a novel
      molecular biomarker in human breast cancer.

PMID- 18346457
TI  - Protein acetylation sites mediated by Schistosoma mansoni GCN5.
AB  - The transcriptional co-activator GCN5, a histone acetyltransferase (HAT), is part
      of large multimeric complexes that are required for chromatin remodeling and
      transcription activation. As in other eukaryotes, the DNA from the parasite
      Schistosome mansoni is organized into nucleosomes and the genome encodes
      components of chromatin-remodeling complexes. Using a series of synthetic
      peptides we determined that Lys-14 of histone H3 was acetylated by the
      recombinant SmGCN5-HAT domain. SmGCN5 was also able to acetylate schistosome non
      histone proteins, such as the nuclear receptors SmRXR1 and SmNR1, and the co
      activator SmNCoA-62. Electron microscopy revealed the presence of SmGCN5 protein
      in the nuclei of vitelline cells. Within the nucleus, SmGCN5 was found to be
      located in interchromatin granule clusters (IGCs), which are transcriptionally
      active structures. The data suggest that SmGCN5 is involved in transcription
      activation.

PMID- 18346458
TI  - Computational analyses of JAK1 kinase domain: subtle changes in the catalytic
      cleft influence inhibitor specificity.
AB  - The Janus kinases (JAKs) are a family of intracellular non-receptor tyrosine
      kinases which transmit signals by phosphorylation of downstream substrates. A
      myriad of cytokines can trigger the JAK-STAT pathway which influences immune
      response, embryonic development, and cellular transformation. Here, we built a
      comparative model for Jak1 based on the crystal structure of Jak2 (PDB code:2B7A)
      and Jak3 (PDB code: 1YVJ) using the InsightII package. 3D-Profile and
      stereochemical analysis further verified the validity of the proposed structure.
      Adenosine 5'-triphosphate (ATP) was then docked into its catalytic cleft.
      Although the shape of Jak1 kinase cleft is fairly similar to that of Jak3, we
      observed minute changes in the key residues of the binding interface which
      influenced the docking of a specific Jak3 inhibitor, WHI-P131. Superimposition of
      the interface residues suggested that substitution of Asp 99 (Jak3) into Glu 101
      (Jak1) generated steric hindrance and a Tyr 91 to Phe 93 switch altered the shape
      of catalytic cleft which collectively prohibited the inhibitor binding.
      Furthermore, in-silico mutagenesis of these two residues back to Asp and Tyr
      enabled Jak1 to accommodate WHI-P131. These results may provide clues for the
      design and optimization of selective kinase inhibitors.

PMID- 18346459
TI  - GITR ligand-costimulation activates effector and regulatory functions of CD4+ T
      cells.
AB  - Engagement of glucocorticoid-induced TNFR-related protein (GITR) enables the
      costimulation of both CD25(-)CD4(+) effector (Teff) and CD25(+)CD4(+) regulatory
      (Treg) cells; however, the effects of GITR-costimulation on Treg function remain
      controversial. In this study, we examined the effects of GITR ligand (GITRL)
      binding on the respective functions of CD4(+) T cells. GITRL-P815 transfectants
      efficiently augmented anti-CD3-induced proliferation and cytokine production by
      Teff cells. Proliferation and IL-10 production in Treg were also enhanced by
      GITRL transfectants when exogenous IL-2 and stronger CD3 stimulation was
      provided. Concomitant GITRL-costimulation of Teff and Treg converted the anergic
      state of Treg into a proliferating state, maintaining and augmenting their
      function. Thus, GITRL-costimulation augments both effector and regulatory
      functions of CD4(+) T cells. Our results suggest that highly activated and
      increased ratios of Treg reverse the immune-enhancing effects of GITRL
      costimulation in Teff, which may be problematic for therapeutic applications
      using strong GITR agonists.

PMID- 18346460
TI  - Decorin expression in quiescent myogenic cells.
AB  - Satellite cells are quiescent muscle stem cells that promote postnatal muscle
      growth and repair. When satellite cells are activated by myotrauma, they
      proliferate, migrate, differentiate, and ultimately fuse to existing myofibers.
      The remainder of these cells do not differentiate, but instead return to
      quiescence and remain in a quiescent state until activation begins the process
      again. This ability to maintain their own population is important for skeletal
      muscle to maintain the capability to repair during postnatal life. However, the
      mechanisms by which satellite cells return to quiescence and maintain the
      quiescent state are still unclear. Here, we demonstrated that decorin mRNA
      expression was high in cell cultures containing a higher ratio of quiescent
      satellite cells when satellite cells were stimulated with various concentrations
      of hepatocyte growth factor. This result suggests that quiescent satellite cells
      express decorin at a high level compared to activated satellite cells.
      Furthermore, we examined the expression of decorin in reserve cells, which were
      undifferentiated myoblasts remaining after induction of differentiation by serum
      deprivation. Decorin mRNA levels in reserve cells were higher than those in
      differentiated myotubes and growing myoblasts. These results suggest that decorin
      participates in the quiescence of myogenic cells.

PMID- 18346461
TI  - Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to
      balance immunotherapy and susceptibility to infection.
AB  - Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have
      immunosuppressive effects which make these molecules candidates for treating
      inflammatory symptoms associated with cardiovascular disease, obesity, arthritis,
      and asthma. However, immunosuppression by PUFAs could increase susceptibility to
      bacterial and viral infection. A detailed molecular picture is required in order
      to understand the balance between the benefits and risks of utilizing PUFAs as
      adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs
      into membrane lipids of antigen presenting cells (APCs) downregulates APC
      function. We propose that PUFAs modulate antigen presentation by altering the
      organization of lipid and protein molecules of the plasma membrane and
      endomembranes; this alters recognition and responses by T cells. The foundation
      of our hypothesis is built on data from artificial bilayer experiments which
      provide the physical principles by which PUFA acyl chains affect membrane
      architecture. This review also reconciles conflicting results in the literature
      by discussing the advantages and disadvantages of differing methods of PUFA
      treatment of cells. We suggest that membrane modulation of immune cells may be an
      important and overlooked mechanism of immunomodulation. In addition, we propose
      that mechanistic studies with defined experimental protocols will speed the
      translation of laboratory studies on PUFAs to the clinic.

PMID- 18346462
TI  - Docosahexaenoic acid: a most unusual fatty acid.

PMID- 18346465
TI  - Comparison of the PTS1- and Rab8b-binding properties of Pex5p and Pex5Rp/TRIP8b.
AB  - Tetratricopeptide (TPR)-domain proteins are involved in various cellular
      processes. The TPR domain is known to be responsible for interaction with other
      proteins commonly recognizing sequence motifs at the C-termini. One such TPR
      protein, TRIP8b, was originally identified in rat as an interaction partner of
      Rab8b, and its human orthologue as a protein related to the peroxisomal targeting
      signal 1 (PTS1) receptor Pex5p (Pex5Rp). Somewhat later, the mouse orthologue was
      reported to bind the hyperpolarization-activated, cyclic nucleotide-regulated HCN
      channels, and, very recently, the rat orthologue was shown to interact with
      latrophilin 1, the calcium-independent receptor of alpha-latrotoxin. Here we
      employed various methodological approaches to investigate and compare the binding
      specificities of the human PTS1 receptor Pex5p and the related protein
      Pex5Rp/TRIP8b towards a subset of targets, including Rab8b and various C-termini
      resembling PTS1. The results show that the TPR domains of Pex5p and Pex5Rp/TRIP8b
      have distinct but overlapping substrate specificities. This suggests that
      selectivity in the recognition of substrates by the TPR domains of Pex5p and
      Pex5Rp/TRIP8b is a matter of considerable complexity, and that no single
      determinant appears to be sufficient in unambiguously defining a binding target
      for either protein. This idea is further corroborated by our observations that
      changes in the surrounding residues or the conformational state of one of the
      binding partners can profoundly alter their binding activities. The implications
      of these findings for the possible peroxisome-related functions of Pex5Rp/TRIP8b
      are discussed.

PMID- 18346463
TI  - Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon
      cancer risk and inflammatory disorders of the intestine.
AB  - A growing body of epidemiological, clinical, and experimental evidence has
      underscored both the pharmacological potential and the nutritional value of
      dietary fish oil enriched in very long chain n-3 PUFAs such as docosahexaenoic
      acid (DHA, 22:6, n-3) and eicosapentaenoic acid (EPA, 20:5, n-3). The broad
      health benefits of very long chain n-3 PUFAs and the pleiotropic effects of
      dietary fish oil and DHA have been proposed to involve alterations in membrane
      structure and function, eicosanoid metabolism, gene expression and the formation
      of lipid peroxidation products, although a comprehensive understanding of the
      mechanisms of action has yet to be elucidated. In this review, we present data
      demonstrating that DHA selectively modulates the subcellular localization of
      lipidated signaling proteins depending on their transport pathway, which may be
      universally applied to other lipidated protein trafficking. An interesting
      possibility raised by the current observations is that lipidated proteins may
      exhibit different subcellular distribution profiles in various tissues, which
      contain a distinct membrane lipid composition. In addition, the current findings
      clearly indicate that subcellular localization of proteins with a certain
      trafficking pathway can be subjected to selective regulation by dietary
      manipulation. This form of regulated plasma membrane targeting of a select subset
      of upstream signaling proteins may provide cells with the flexibility to
      coordinate the arrangement of signaling translators on the cell surface.
      Ultimately, this may allow organ systems such as the colon to optimally decode,
      respond, and adapt to the vagaries of an ever-changing extracellular environment.

PMID- 18346464
TI  - Regulation of EP4 expression via the Sp-1 transcription factor: inhibition of
      expression by anti-cancer agents.
AB  - For glioblastomas, COX-2 expression is linked to poor survival. COX-2 effects are
      mediated by the receptors EP2 and EP4, whose regulation is poorly understood. The
      expression of EP4, and activation or inhibition of EP4 activity in human
      glioblastoma T98G cells, was found to correlate with growth on soft agar.
      Chemoprevention drugs, troglitazone (TGZ) and some COX inhibitors, significantly
      suppressed EP4 expression in T98G cells in a dose dependant manner. Specificity
      protein 1 (Sp-1) binding sites, located within region -197 to -160 of the human
      EP4 promoter, are important for the transcription initiation of the human EP4
      gene and are responsible for the EP4 suppression by TGZ. Mutation in the Sp-1
      sites altered the promoter activity of luciferase constructs and TGZ effects on
      the promoter. The inhibitory effect of TGZ on EP4 expression was reversed by
      PD98059, a MEK-1/Erk inhibitor. Immunoprecipitation-Western blot analysis
      detected Sp-1 phosphorylation that was dependent on TGZ-induced Erks activation.
      ChIP assay confirmed that Sp-1 phosphorylation decreases its binding to DNA and
      as a result, leads to the suppression of EP4 expression. Thus, we propose that
      the expression of EP4 is regulated by Sp-1, but phosphorylation of Sp-1 induced
      by TGZ suppresses this expression. This represents a new and unique mechanism for
      the regulation of the EP4 receptor expression.

PMID- 18346466
TI  - The secretion and maturation of prosaposin and procathepsin D are blocked in
      embryonic neural progenitor cells.
AB  - The notion that prosaposin (Prosap) is likely involved in brain development and
      regeneration led us to explore its expression in stem/progenitor neural cells and
      its fate after cell differentiation. The expression of procathepsin-cathepsin D
      (proCath-Cath D), an endoprotease that plays an important role in the processing
      and sorting of Prosap, has been concomitantly examined. Our data evidenced that
      in embryonic human neural progenitor cells (eHNPCs) intact and high molecular
      weight intermediate forms of Prosap and intermediate forms of Cath D accumulated
      inside the cells, while the formation of saposins and mature Cath D was impaired.
      Furthermore, neither Prosap nor proCath D were secreted from eHNPCs. The block of
      the processing and secretion shared by Prosap and proCath D was overcome during
      the course of differentiation of eHNPCs into a mixed population of astrocytes and
      neuronal cells. Upon differentiation, large amounts of Prosap and proCath D were
      secreted from the cells, while saposins and mature Cath D were produced inside
      the cells. The dramatic accumulation of Prosap (an antiapoptotic factor) and
      reduction of mature Cath D (a proapoptotic factor) in the undifferentiated eHNPCs
      most likely play a role in the molecular mechanisms regulating the resistance to
      apoptotic signals of these cells and might represent a critically important issue
      in HNPCs biology.

PMID- 18346467
TI  - Direct Thy-1/alphaVbeta3 integrin interaction mediates neuron to astrocyte
      communication.
AB  - Thy-1 is an abundant neuronal glycoprotein of poorly defined function. We
      recently provided evidence indicating that Thy-1 clusters a beta3-containing
      integrin in astrocytes to induce tyrosine phosphorylation, RhoA activation and
      the formation of focal adhesions and stress fibers. To date, the alpha subunit
      partner of beta3 integrin in DI TNC1 astrocytes is unknown. Similarly, the
      ability of neuronal, membrane-bound Thy-1 to trigger astrocyte signaling via
      integrin engagement remains speculation. Here, evidence that alphav forms an
      alphavbeta3 heterodimer in DI TNC1 astrocytes was obtained. In neuron-astrocyte
      association assays, the presence of either anti-alphav or anti-beta3 integrin
      antibodies reduced cell-cell interaction demonstrating the requirement of both
      integrin subunits for this association. Moreover, anti-Thy-1 antibodies blocked
      stimulation of astrocytes by neurons but not the binding of these two cell types.
      Thus, neuron-astrocyte association involved binding between molecular components
      in addition to the Thy-1-integrin; however, the signaling events leading to focal
      adhesion formation in astrocytes depended exclusively on the latter interaction.
      Additionally, wild-type (RLD) but not mutated (RLE) Thy-1 was shown to directly
      interact with alphavbeta3 integrin by Surface Plasmon Resonance analysis. This
      interaction was promoted by divalent cations and was species-independent.
      Together, these results demonstrate that the alphavbeta3 integrin heterodimer
      interacts directly with Thy-1 present on neuronal cells to stimulate astrocytes.

PMID- 18346468
TI  - Role of the carboxyl terminal di-leucine in phosphorylation and internalization
      of C5a receptor.
AB  - The carboxyl tail of G protein-coupled receptors contains motifs that regulate
      receptor interactions with intracellular partners. Activation of the human
      neutrophil complement fragment C5a receptor (C5aR) is terminated by
      phosphorylation of the carboxyl tail followed by receptor internalization. In
      this study, we demonstrated that bulky hydrophobic residues in the membrane
      proximal region of the C5aR carboxyl tail play an important role in proper
      structure and function of the receptor: Substitution of leucine 319 with alanine
      (L319A) resulted in receptor retention in the endoplasmic reticulum, whereas a
      L318A substitution allowed receptor transport to the cell surface, but showed
      slow internalization upon activation, presumably due to a defect in
      phosphorylation by both PKC and GRK. Normal agonist-induced activation of ERK1/2
      and intracellular calcium release suggested that the L318A mutation did not
      affect receptor signaling. Binding of GRK2 and PKCbetaII to intracellular loop 3
      of C5aR in vitro indicated that mutagenesis of L318 did not affect kinase
      binding. Limited proteolysis with trypsin revealed a conformational difference
      between wild type and mutant receptor. Our studies support a model in which the
      L318/L319 stabilizes an amphipathic helix (Q305-R320) in the membrane-proximal
      region of C5aR.

PMID- 18346469
TI  - Increase in P-glycoprotein accompanied by activation of protein kinase Calpha and
      NF-kappaB p65 in the livers of rats with streptozotocin-induced diabetes.
AB  - It is known that protein kinase C (PKC) signal transduction is enhanced in a
      diabetic state, and that PKC activator phorbol esters increase the gene
      expression of MDR1 in human tumor cells. To clarify the expression of the liver
      transporters under diabetic conditions and the roles of PKCalpha and the
      transcription factor NF-kappaB, we investigated the expression levels of Mdr1a,
      Mdr1b, Mdr2, Mrp2, Bcrp, Bsep, Oct1, Oat2, and Oat3 transporters, PKCalpha,
      IkappaB, and NF-kappaB in the liver of rats with STZ-induced hyperglycemia. A
      selective increase in the gene expression of Mdr1b was detected by RT-PCR.
      Western blotting with C219 antibody revealed an increase in P-glycoprotein.
      Although the mRNA level of PKCalpha was not affected, translocation of PKCalpha
      to the microsomal fraction was detected. NF-kappaB p65, IkappaBalpha and
      IkappaBbeta mRNA levels were increased as was the level of nuclear NF-kappaB p65.
      From these findings, it was suggested that STZ-induced hyperglycemia caused the
      upregulation of Mdr1b P-gp expression through the activation of PKCalpha and NF
      kappaB.

PMID- 18346470
TI  - Fatty acids influence binding of cobalt to serum albumin in patients with fatty
      liver.
AB  - Human serum albumin binds ligands such as fatty acids and metals in circulation.
      Oxidative stress can modify albumin and affect ligand binding. This study
      examines the role of oxidative stress and fatty acids in modulating cobalt
      binding to albumin in patients with fatty liver. Elevated levels of
      malondialdehyde and protein carbonyls, indicative of oxidative stress were
      evident in serum of patients with fatty liver. A significant decrease in albumin
      cobalt binding was also observed. Albumin isolated from patient serum also showed
      an increase in bound fatty acids. In vitro experiments indicated that while
      oxidant exposure or removal of fatty acids independently decreased cobalt binding
      to albumin, removal of fatty acids from the protein prior to oxidant exposure did
      not influence the oxidant effect on albumin-cobalt binding. These results suggest
      that oxidative stress and fatty acids on albumin can influence albumin-cobalt
      binding in patients with fatty liver by independent mechanisms.

PMID- 18346471
TI  - Five human phenylalanine hydroxylase proteins identified in mild
      hyperphenylalaninemia patients are disease-causing variants.
AB  - Hyperphenylalaninemia is a group of autosomal recessive disorders caused by a
      wide range of phenylalanine hydroxylase (PAH) gene variants. To study the effects
      of mutations on PAH activity, we have reproduced five mutations (p.N223Y,
      p.R297L, p.F382L, p.K398N and p.Q419R) that we recently identified in a
      population of Southern Italy. Transient expression of mutant full-length cDNAs in
      human HEK293 cells yielded PAH variants whose l-phenylalanine hydroxylase
      activity was between 40% and 70% that of the wild-type enzyme. Moreover, Western
      blot analysis revealed a 50-kD monomer in all mutants thereby indicating normal
      synthesis of the mutant proteins. Because of the clinical mild nature of the
      phenotypes we performed an in vivo BH4 loading test. This was positive in all
      tested patients, which indicates that they are likely to respond to the coenzyme
      in vivo. We also analysed the environment of each mutation site in the available
      crystal structures of PAH by using molecular graphics tools. The structural
      alteration produced by each mutation was elucidated and correlated to the mutated
      properties of the mutant enzymes. All the data obtained demonstrate the disease
      causing nature of the five novel variants.

PMID- 18346472
TI  - Dietary fructose induces a wide range of genes with distinct shift in
      carbohydrate and lipid metabolism in fed and fasted rat liver.
AB  - Dietary fructose has been suspected to contribute to development of metabolic
      syndrome. However, underlying mechanisms of fructose effects are not well
      characterized. We investigated metabolic outcomes and hepatic expression of key
      regulatory genes upon fructose feeding under well defined conditions. Rats were
      fed a 63% (w/w) glucose or fructose diet for 4 h/day for 2 weeks, and were killed
      after feeding or 24-hour fasting. Liver glycogen was higher in the fructose-fed
      rats, indicating robust conversion of fructose to glycogen through
      gluconeogenesis despite simultaneous induction of genes for de novo lipogenesis
      and increased liver triglycerides. Fructose feeding increased mRNA of previously
      unidentified genes involved in macronutrient metabolism including fructokinase,
      aldolase B, phosphofructokinase-1, fructose-1,6-bisphosphatase and carbohydrate
      response element binding protein (ChREBP). Activity of glucose-6-phosphate
      dehydrogenase, a key enzyme for ChREBP activation, remained elevated in both fed
      and fasted fructose groups. In the fasted liver, the fructose group showed lower
      non-esterified fatty acids, triglycerides and microsomal triglyceride transfer
      protein mRNA, suggesting low VLDL synthesis even though plasma VLDL triglycerides
      were higher. In conclusion, fructose feeding induced a broader range of genes
      than previously identified with simultaneous increase in glycogen and
      triglycerides in liver. The induction may be in part mediated by ChREBP.

PMID- 18346473
TI  - Fourier transform coupled to tryptophan-scanning mutagenesis: lessons from its
      application to the prediction of secondary structure in the acetylcholine
      receptor lipid-exposed transmembrane domains.
AB  - Although Fourier transform (FT) and tryptophan-scanning mutagenesis (TrpScanM)
      have been extremely useful for predicting secondary structures of membrane
      proteins, they are deemed to be low-resolution techniques. Herein, we describe
      the combined use of FT and TrpScanM (FT-TrpScanM) as a more reliable approach for
      the prediction of secondary structure. Five TrpScanM studies of the acetylcholine
      receptor lipid-exposed transmembrane domains (LETMDs) were revisited and analyzed
      by FT-TrpScanM. FT analysis of the raw data from the aforementioned TrpScanM
      studies supports and validates the conclusions derived from their tryptophan
      periodicity profiles. Furthermore, by FT-TrpScanM, we were able to determine the
      minimum number of consecutive tryptophan substitutions necessary for more robust
      prediction of alpha-helical secondary structures and evaluate the quality of
      structure predictions by alpha-helical character curves. Finally, this study
      encourages future utilization of FT-TrpScanM to more reliably predict secondary
      structures of the membrane protein LETMDs.

PMID- 18346475
TI  - Recent advances in thyroid cancer. Foreword.

PMID- 18346474
TI  - Converting human carbonic anhydrase II into a benzoate ester hydrolase through
      rational redesign.
AB  - Enzymes capable of benzoate ester hydrolysis have several potential medical and
      industrial applications. A variant of human carbonic anhydrase II (HCAII) was
      constructed, by rational design, that is capable of hydrolysing para-nitrophenyl
      benzoate (pNPBenzo) with an efficiency comparable to some naturally occurring
      esterases. The design was based on a previously developed strategy [G. Host, L.G.
      Martensson, B.H. Jonsson, Redesign of human carbonic anhydrase II for increased
      esterase activity and specificity towards esters with long acyl chains, Biochim.
      Biophys. Acta 1764 (2006) 1601-1606.], in which docking of a transition state
      analogue (TSA) to the active site of HCAII was used to predict mutations that
      would allow the reaction. A triple mutant, V121A/V143A/T200A, was thus
      constructed and shown to hydrolyze pNPBenzo with k(cat)/K(M)=625 (+/- 38) M(-1)
      s(-1). It is highly active with other ester substrates as well, and hydrolyzes
      para-nitrophenyl acetate with k(cat)/K(M)=101,700 (+/- 4800) M(-1) s(-1), which
      is the highest esterase efficiency so far for any CA variant. A parent mutant
      (V121A/V143A) has measurable K(M) values for para-nitrophenyl butyrate (pNPB) and
      valerate (pNPV), but for V121A/V143A/T200A no K(M) could be determined, showing
      that the additional T200A mutation has caused a decreased substrate binding.
      However, k(cat)/K(M) is higher with both substrates for the triple mutant,
      indicating that binding energy has been diverted from substrate binding to
      transition state stabilization.

PMID- 18346476
TI  - Recent advances in thyroid cancer. In brief.

PMID- 18346477
TI  - Recent advances in thyroid cancer.

PMID- 18346478
TI  - Leukemias. Foreword.

PMID- 18346479
TI  - Acute leukemia in children.

PMID- 18346480
TI  - Acute leukemias in adults.

PMID- 18346481
TI  - Chronic leukemias.

PMID- 18346482
TI  - Brucellosis in camels (Camelus dromedarius) in Darfur, Western Sudan.
AB  - In a field outbreak of brucellosis in 21 camels mixed with cattle, sheep and
      goats, five camels, three of which showed clinical signs, were serologically
      positive. In a subsequent abattoir survey of apparently healthy camels, six
      animals were seropositive, albeit with titres that tended to be lower than those
      found in the field outbreak. Of the six seropositive slaughtered camels, five
      were shown to have lymph nodes (prescapular and supramammary) infected with
      brucellae (Brucella melitensis biovar 3, two camels; Brucella abortus biovar 6,
      three camels). Infection of camels with B. abortus biovar 6 had not previously
      been reported. Infection of the supramammary lymph nodes presents a potential
      hazard to those who consume raw camels' milk, a common practice in nomadic camel
      owners.

PMID- 18346492
TI  - Integrating oral health to the care of overweight children: a model of care whose
      time has come.

PMID- 18346493
TI  - Understanding transition issues: asthma as an example.

PMID- 18346494
TI  - Removing the mask: the danger of hidden hypertension.

PMID- 18346495
TI  - Hypoplastic left heart syndrome--the rest of the story.

PMID- 18346496
TI  - Primary care management of the childhood cancer survivor.

PMID- 18346497
TI  - Is it possible to protect pediatric research subjects without blocking
      appropriate research?

PMID- 18346498
TI  - Transition to adulthood: delays and unmet needs among adolescents and young
      adults with asthma.
AB  - OBJECTIVE: To examine the effect of the transition to adulthood on financial and
      non-financial barriers to care in youth with asthma. STUDY DESIGN: With National
      Health Interview Survey data from 2000 to 2005, we examined delays and unmet
      needs because of financial and non-financial barriers, evaluating the effect of
      adolescent (age, 12-17 years; n = 1539) versus young adult age (age, 18-24 years;
      N = 833), controlling for insurance, usual source of care, and sociodemographic
      characteristics. We also simulated the effects of providing public insurance to
      uninsured patients and a usual source of care to patients without one. RESULTS:
      More young adults than adolescents encountered financial barriers resulting in
      delays (18.6% versus 8%, P < .05) and unmet needs (26.6% versus 11.4%, P < .05),
      although delays caused by non-financial barriers were similar (17.3% versus
      14.9%, P = not significant). In logistic models young adults were more likely
      than adolescents to report delays (odds ratio [OR], 1.45; 95% CI, 1.02-2.08) and
      unmet needs (OR, 1.8; 95% CI, 1.29-2.52) caused by financial barriers.
      CONCLUSIONS: Delays and unmet needs for care caused by financial reasons are
      significantly higher for young adults than they are for adolescents with asthma.

PMID- 18346499
TI  - The Pediatric Respiratory Assessment Measure: a valid clinical score for
      assessing acute asthma severity from toddlers to teenagers.
AB  - OBJECTIVE: To determine the performance characteristics of the Preschool
      Respiratory Assessment Measure (PRAM) in preschool and school-aged children with
      acute asthma. STUDY DESIGN: In a prospective cohort study, we examined the
      validity, responsiveness, and reliability of the PRAM in children aged 2 to 17
      years with acute asthma. The study involved more than 100 nurses and physicians
      who recorded the PRAM on triage, after initial bronchodilation, and at
      disposition. Predictive validity and responsiveness were examined using
      disposition as outcome. RESULTS: The PRAM was recorded in 81% (n = 782) of
      patients at triage. The PRAM at triage and after initial bronchodilation showed a
      strong association with admission (r = 0.4 and 0.5, respectively; P < .0001),
      thus supporting its ability to distinguish across severity levels. The
      responsiveness coefficient of 0.7 indicated good ability to identify change after
      bronchodilation. The PRAM showed good internal consistency (Cronbach alpha =
      0.71) and inter-rater reliability (r = 0.78) for all patients and across all age
      groups. CONCLUSIONS: Good performance characteristics were observed in all age
      groups, making the PRAM an attractive score for assessing asthma severity and
      response to treatment.

PMID- 18346500
TI  - Health plan notification and feedback to providers is associated with increased
      filling of preventer medications for children with asthma enrolled in Medicaid.
AB  - OBJECTIVE: To test the hypothesis that children enrolled in Medicaid managed care
      health plans that provide asthma-specific communication to providers would be
      more likely to have adequate asthma medication filling. STUDY DESIGN: We
      conducted a historical cohort study of 4498 children (2-17 years old) with
      moderate-severe asthma in Washington State and Tennessee Medicaid managed care
      programs from 2000 to 2002. Interviews with health plans were conducted to
      identify communication strategies health plans used to improve asthma care by
      providers in the plan. The main outcome measure was guideline-recommended filling
      of asthma preventer medications. RESULTS: Children in plans that provided
      specific feedback to providers about asthma quality and notified providers when
      children had an asthma-related event had the highest mean days plus or minus SE
      of filling in the 365-day follow-up period (164.6 +/- 13 days) compared with
      children in plans with neither (135.3 +/- 10.8 days; P < .05). In children with
      the greatest asthma severity, enrollment in a plan with both features was
      associated with 27.1 additional days of filling (95% CI, 0.7-53.4 days) during
      the follow-up period. CONCLUSION: Health plan communication to providers was
      associated with increased preventer filling in children with moderate-severe
      asthma in 2 state Medicaid programs.

PMID- 18346502
TI  - Associations among obesity, blood pressure, and left ventricular mass.
AB  - OBJECTIVES: To measure resting and ambulatory systemic blood pressure (BP) and
      left ventricular mass (LVM) in prepubertal obese and lean children and to
      determine their relationships. STUDY DESIGN: Cross-sectional study including 44
      obese and 22 lean prepubertal children (mean age 8.8 +/- 1.5 years). We measured
      casual and 24-hour ambulatory BP, LVM and LVM index (LVMI) by echocardiography,
      and whole body lean tissue and fat mass by dual-energy X-ray absorptiometry.
      RESULTS: Mean 24-hour systolic BP (124.8 +/- 14.2 vs 105.5 +/- 8.8 mm Hg),
      diastolic BP (72.8 +/- 7.3 vs 62.7 +/- 3.8 mm Hg), and LVMI (36.1 +/- 5.8 vs 30.9
      +/- 5.7, g x m(-2.7)) were significantly higher in obese than in lean subjects.
      Systolic ambulatory hypertension was present in 47.6% of obese children, and
      casual BP was normal in 55% of those cases. Body fatness, lean tissue mass, and
      24-hour BP correlated positively with LVMI. When adjusted for body fatness, LVMI
      was only associated with 24-hour systolic BP (adjusted R(2) = 15.9%; P = .001).
      CONCLUSIONS: Ambulatory systemic hypertension and increased LVM are found in
      obese children. Left ventricular mass is partially determined by systemic BP. We
      conclude that prevention and treatment of childhood obesity should be initiated
      as early as possible to prevent the premature development of hypertension and end
      stage organ damage.

PMID- 18346503
TI  - The efficacy of a clinic-based behavioral nutrition intervention emphasizing a
      DASH-type diet for adolescents with elevated blood pressure.
AB  - OBJECTIVE: To examine the efficacy of a 3-month clinic-based behavioral nutrition
      intervention emphasizing a diet high in fruits, vegetables, and low fat dairy
      (DASH intervention) versus routine outpatient hospital-based nutrition care (RC)
      on diet and blood pressure (BP) in adolescents with elevated BP. STUDY DESIGN:
      Fifty-seven adolescents with a clinical diagnosis of prehypertension or
      hypertension (systolic BP or diastolic BP, 90(th) to 99(th) percentile) were
      randomly assigned to DASH or RC. SBP, DBP, 3-day diet recall, weight, and height
      were assessed at pretreatment, post-treatment, and 3 months later (follow-up).
      RESULTS: In completer analysis, DASH versus RC had a greater decrease in SBP z
      scores from baseline to post-treatment (P < 0.01) and a trend for a greater
      decrease in SBP z scores from baseline through follow-up (P = .07). DBP z scores
      changed similarly for conditions from baseline through follow-up. Relative to RC,
      DASH had a greater increase in intake of fruits (P < .001), potassium and
      magnesium (P < .01), and a greater decrease in total fat (P < .05) from baseline
      to post-treatment. From baseline through follow-up, DASH versus RC had a greater
      increase in low fat dairy (P < .001). CONCLUSIONS: The DASH intervention proved
      more effective than RC in improving SBP and diet quality in adolescents with
      elevated BP.

PMID- 18346504
TI  - Body dissatisfaction, self-esteem, and depression in obese Korean children.
AB  - OBJECTIVES: To investigate the relationship between obesity and psychological
      well being in children and to examine the mediation effect of body
      dissatisfaction on mental health of obese Korean children. STUDY DESIGN: A total
      of 413 Korean children in grades 5 and 6 from 3 elementary schools completed self
      reporting questionnaires on body dissatisfaction, self-esteem, and level of
      depressive symptoms. A sex-specific body mass index for age at or the above the
      95th percentile was defined as obese, and that between the 85th and 94th
      percentiles was defined as overweight. RESULTS: Obese children demonstrated
      higher body dissatisfaction and lower self-esteem than normal weight and
      overweight peers (P = 0 and .008, respectively), but not more depression. Body
      dissatisfaction mediated the association between obesity and self-esteem. The
      obese children with body dissatisfaction had significantly lower self-esteem and
      higher levels of depressive symptoms than the obese children without body
      dissatisfaction and normal weight children (P = 0). CONCLUSIONS: Our findings
      suggest that childhood obesity may be linked to body dissatisfaction, leading to
      low self-esteem and high levels of depressive symptoms.

PMID- 18346505
TI  - Decreased exercise performance with age in children with hypoplastic left heart
      syndrome.
AB  - OBJECTIVE: Children born with hypoplastic left heart syndrome (HLHS) may
      experience cardiac dysfunction after staged surgery or transplantation, which may
      worsen with age. We examined the hypothesis that exercise testing can address
      cardiovascular capacity and suggest interventions to improve quality of life.
      STUDY DESIGN: Children with HLHS > or = 8 years old performed treadmill or
      bicycle ergometric testing at 4 centers. Results were compared with norms for age
      and sex. RESULTS: Of the 42 participants, the mean age was 12.9 years (range, 8.5
      17.0 years), 64% were boys, 20 had staged surgery, and 34 completed metabolic
      assessment. The percent of predicted maximal oxygen uptake (mVO2) was higher in
      younger children. Children aged 8 to 12 years achieved 70% of predicted mVO2;
      children aged 13 to 17 years achieved 60% of predicted mVO2 (P = .02). The
      percent of predicted peak heart rate trended higher in younger patients (83%
      versus 75%, P = .07). Electrocardiographic changes were more common in older
      children. In treadmill testing, patients who had a transplant had better exercise
      performance than patients who underwent staged surgery in percent of predicted
      exercise time (82% versus 54%, P < .0001) and peak rate-pressure product (241 x
      10(3) versus 195 x 10(3), P = .02). The percent of predicted mVO2 did not differ
      between patients who had a transplant (66%) and patients who underwent staged
      surgery (61%, P = .25). CONCLUSION: Children with HLHS showed considerable age
      related decline in exercise performance, regardless of surgical strategy.

PMID- 18346506
TI  - Brain volume reductions within multiple cognitive systems in male preterm
      children at age twelve.
AB  - OBJECTIVES: To more precisely examine regional and subregional microstructural
      brain changes associated with preterm birth. STUDY DESIGN: We obtained brain
      volumes from 29 preterm children, age 12 years, with no ultrasound scanning
      evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in
      the newborn period, and 22 age- and sex-matched term control subjects. RESULTS:
      Preterm male subjects demonstrated significantly lower white matter volumes in
      bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex,
      superior and inferior longitudinal fasciculi compared with term male subjects.
      Gray matter volumes in prefrontal cortex, basal ganglia, and temporal lobe also
      were significantly reduced in preterm male subjects. Brain volumes of preterm
      female subjects were not significantly different from those of term female
      control subjects. Voxel-based morphometry results were not correlated with
      perinatal variables or cognitive outcome. Higher maternal education was
      associated with higher cognitive performance in preterm male subjects.
      CONCLUSIONS: Preterm male children continue to demonstrate abnormal
      neurodevelopment at 12 years of age. However, brain morphology in preterm female
      children may no longer differ from that of term female children. The
      neurodevelopmental abnormalities we detected in preterm male subjects appear to
      be relatively diffuse, involving multiple neural systems. The relationship
      between aberrant neurodevelopment and perinatal variables may be mediated by
      genetic factors, environmental factors, or both reflected in maternal education
      level.

PMID- 18346508
TI  - Potential interactions of drug-natural health products and natural health
      products-natural health products among children.
AB  - OBJECTIVE: To determine the frequency of concurrent use of conventional
      medications and natural health products (NHP) and their potential interactions in
      children arriving at an emergency department. STUDY DESIGN: A survey of parents
      and patients 0 to 18 years at a large pediatric ED in Toronto, Ontario, Canada.
      RESULTS: A total of 1804 families were interviewed in this study. Concurrent drug
      NHP use was documented in 355 (20%) of patients and 269 (15%) of NHP users were
      receiving more than one NHP simultaneously. Theoretically possible NHP-drug or
      NHP-NHP interactions in the preceding 3 months were identified in 285 (16%)
      children. There were 35 different NHP-medication interaction pairs and 41 NHP-NHP
      interaction pairs. NHP-medication interactions were predominantly pharmacokinetic
      (modified absorption, 35%); potential NHP-NHP interactions were mostly
      pharmacodynamic (increased risk of bleeding, 47%). CONCLUSIONS: Medications are
      used concurrently with NHP in every fifth pediatric patient in the emergency
      department and many NHP users are receiving more than 1 NHP simultaneously. One
      quarter of all paired medication-NHP or NHP-NHP could potentially cause
      interactions. Although we can not confirm that these were true interactions
      resulting in clinical symptoms, parents and health care providers need to balance
      the potential benefit of concurrent NHP-medication use with its potential harms.

PMID- 18346509
TI  - The placebo response in studies of acute migraine.
AB  - OBJECTIVES: To characterize the magnitude of the placebo response in trials of
      migraine therapy in children and adolescents, and to identify its determinants.
      STUDY DESIGN: MEDLINE and CENTRAL were searched through November 2006 for
      randomized controlled trials or controlled clinical trials of pediatric acute
      migraine pharmacologic treatment that included a placebo comparator group. The
      main outcomes were headache relief and pain-free response, and effect estimates
      for risk differences were calculated whenever possible. The influence of placebo
      response determinants was studied using subgroup analysis. A total of 13 trials
      (1324 participants in the placebo groups) were included in the analysis. RESULTS:
      The pooled placebo responses for pain relief and pain-free at 2 hours were 46%
      (range, 38% to 53%) and 21% (range, 17% to 26%). Parallel studies conducted in
      North American centers demonstrated a significantly higher placebo response, as
      did trials that used 4-point pain scales. Other placebo determinants did not
      influence the effect estimate, although insufficient data were available to study
      some of them. CONCLUSIONS: There is a widely variable placebo response in
      pediatric migraine trials, supporting the continued use of placebo groups and
      suggesting the need for more research into the placebo effect in the pediatric
      population.

PMID- 18346511
TI  - Deep sedation for cardiac magnetic resonance imaging: a comparison with cardiac
      anesthesia.
AB  - OBJECTIVE: To test the hypothesis that safety, efficacy, and image quality in
      pediatric patients who undergo deep sedation for cardiac magnetic resonance
      imaging (CMR) for congenital heart disease (CHD) is similar to general anesthesia
      (GA). STUDY DESIGN: Retrospective review of all CMR records from 1997-2006. Six
      hundred sixty patients underwent deep sedation (DS) and 161 underwent GA.
      Statistics included analysis of variance, chi(2) analysis, and the coefficient of
      variation. RESULTS: Diagnoses included a broad spectrum of CHD. No serious
      adverse events (AE) including mortalities and hospitalizations occurred because
      of DS. There were 18 (2.8%) self-limited events in the DS group with a success
      rate of 97.9%. The AE rate for patients undergoing GA was 3.9% (n = 6), including
      2 overnight hospital stays with a success rate of 100%. AE and success rates did
      not differ between the 2 groups. Observers blinded to the patient's group found
      no difference in image quality. Even in young infants, excellent image quality
      was obtained. CONCLUSIONS: Sedation of appropriately screened pediatric patients
      with CHD undergoing CMR is safe and well tolerated and yields high-quality images
      similar to GA. GA should be considered for patients with CHD with hemodynamic or
      airway compromise, in whom sedation has failed, or who have special
      circumstances.

PMID- 18346512
TI  - Glucose tolerance and insulin secretion, morbidity, and death in patients with
      cystic fibrosis.
AB  - OBJECTIVES: To describe the history, mechanisms, and consequences of cystic
      fibrosis (CF)-related diabetes, from childhood to early adulthood. STUDY DESIGN:
      Pancreatic beta-cell function was estimated from the plasma insulin/glucose
      ratios during oral glucose tolerance test (total area under the curve and
      deltaI(30-0min)/G(30min), homeostasis model assessment [HOMA]%B), insulin
      sensitivity with the HOMA%S index, in 237 children with CF (109 boys, 128 girls).
      Progression of glucose metabolism abnormalities was evaluated by analysis for
      interval censored data; rates of pulmonary transplantation and death by Kaplan
      Meier analysis. RESULTS: Impaired glucose tolerance was found in 20% of patients
      at 10 years, 50% at 15 years, 75% at 20 years, 82% at 30 years; for diabetes,
      >20% at 15 year, 45% at 20 years, 70% at 30 years; for insulin treatment, 30% at
      20 years, 40% at 30 years. Early impairment was associated with lower survival
      rates and higher rates of lung transplantation. The area under the curve(glucose)
      correlated with decreased body mass index and height. Decrease in early insulin
      secretion (deltaI(30-0min)/G(30min)) was associated with impaired glucose
      tolerance, in all estimates of insulin secretion with diabetes. HOMA%S did not
      differ between the groups. Increased inflammation correlated with insulin
      resistance and impaired glucose tolerance. CONCLUSIONS: CF-related diabetes,
      mainly because of beta-cell deficiency, is frequent early in life and associated
      with impaired nutritional state and growth, increased rates of terminal
      respiratory failure, and death.

PMID- 18346513
TI  - [(11)C]flumazenil positron emission tomography analyses of brain gamma
      aminobutyric acid type A receptors in Angelman syndrome.
AB  - OBJECTIVE: To evaluate the role of the gamma-aminobutyric acid type A (GABA(A))
      receptor in Angelman syndrome (AS). STUDY DESIGN: We performed [(11)C]flumazenil
      positron emission tomography (PET) and examined GABA(A) receptor expression in 7
      patients with AS of various genotypes (5 with the deletion, 1 with an imprinting
      defect [ID], and 1 with a UBE3A mutation) and 4 normal control healthy
      volunteers. RESULTS: Relative to the control subjects, the [(11)C]flumazenil
      binding potentials (BPs) were significantly higher in the cerebral cortex and
      cerebellum in the 5 patients with the deletion and in the 1 patient with a UBE3A
      mutation, and were less frequently or barely increased in adult patients with the
      deletion and in the patient with IDs. CONCLUSIONS: Total GABA(A) receptor
      expression was increased in patients with AS with various genotypes. We suggest
      that a developmental dysregulation of the GABA(A) receptor subunits occurs in
      patients with AS.

PMID- 18346514
TI  - Clinical and laboratory characteristics and long-term outcome of pediatric
      systemic lupus erythematosus: a longitudinal study.
AB  - OBJECTIVES: To determine the frequency and characteristics of clinical signs,
      symptoms, laboratory findings, and medication use in children with pediatric
      systemic lupus erythematosus (pSLE) at presentation and during the course of the
      disease, and to examine correlations among disease manifestations, disease
      activity, and damage over time. STUDY DESIGN: The study involved an analysis of
      medical records and the SLE database of an inception cohort of 256 patients with
      pSLE (female:male ratio, 4.7:1). RESULTS: The most common clinical manifestations
      were arthritis (67%), malar rash (66%), nephritis (55%), and central nervous
      system (CNS) disease (27%). At diagnosis, patients with both renal and CNS
      disease had the highest SLE Disease Activity Index (SLEDAI) scores (P < .0001),
      but these scores were similar to those of the total group at 1 year (P = .11).
      Patients who developed renal and CNS disease more than 1 year after diagnosis had
      higher SLEDAI scores at disease onset. Some 34% of patients had Systemic Lupus
      International Collaborative Clinics Damage Index (SLICC-DI) scores >1 at a mean
      follow-up of 3.5 years. A greater proportion of patients with renal and CNS
      disease had SLICC-DI scores of >1, and these patients had higher mean scores
      compared with patients without major organ involvement (70% vs 11% [P < .0001]
      and 1.4 vs 0.1 [P < .0001], respectively). CONCLUSIONS: Most of the patients in
      our cohort exhibited major organ involvement. These patients had the highest
      SLEDAI scores at diagnosis, which normalized at 1 year but preceded development
      of renal and CNS disease. The average SLICC-DI score was lower than that
      previously reported in patients with pSLE.

PMID- 18346515
TI  - Impaired endothelial function in adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVE: To evaluate the effect of a high-fat meal on endothelial function in
      adolescents with type 1 diabetes mellitus (T1D). STUDY DESIGN: Twenty-three
      children with T1D, aged 12 to 18 years, and age- and sex-matched healthy control
      subjects were assessed for baseline macronutrient intake, and endothelial
      function was measured both fasting and after a standardized fast-food, high-fat
      breakfast. RESULTS: Endothelial function, assessed noninvasively by peripheral
      arterial tonometry, was impaired in the T1D group in the fasting state as
      compared with control subjects (T1D 1.78 +/- 0.4, control subjects 2.06 +/- 0.4,
      P = .02), and worsened postprandially in both groups (T1D 1.45 +/- 0.3, control
      subjects 1.71 +/- 0.3, P = .01). Both groups demonstrated significantly elevated
      triglyceride levels 3.5 hours after ingestion of the high-fat meal (T1D 114.8 +/-
      42.8 and control subjects 126.7 +/- 54.9 mg/dL). Nutrient intake in both groups
      showed higher than recommended intakes of total fat, saturated fat, and
      cholesterol. CONCLUSIONS: Patients with T1D exhibited worse endothelial function
      both before and after a high-fat breakfast than their peers. This suggests that
      patients with T1D are at greater risk of vascular impairment after a high-fat
      meal, the cumulative effect of which may contribute to the higher atherosclerotic
      burden observed in T1D.

PMID- 18346516
TI  - Safety and efficacy of enzyme replacement therapy with agalsidase beta: an
      international, open-label study in pediatric patients with Fabry disease.
AB  - OBJECTIVE: To evaluate the safety and explore the efficacy of enzyme replacement
      therapy with agalsidase beta (recombinant human alpha-galactosidase A; Fabrazyme
      [Genzyme Corporation, Cambridge, MA]) in pediatric patients with Fabry disease, a
      genetic disorder in which deficient endogenous enzyme causes pathogenic tissue
      accumulation of globotriaosylceramide (GL-3). STUDY DESIGN: Fourteen male and 2
      female patients, 8 to 16 years old, were treated in this open-label study. A 12
      week observation period to collect baseline data preceded the 48-week treatment
      period when agalsidase beta (1 mg/kg) was infused intravenously every 2 weeks. No
      primary efficacy end point was specified. RESULTS: Before treatment, results of
      skin biopsies from 12 male patients showed moderate or severe GL-3 accumulation
      in superficial dermal capillary endothelial cells; with treatment, these cells
      were completely cleared of GL-3 in week-24 biopsies from all 12 male patients and
      in all available week-48 biopsies. With treatment, reports of gastrointestinal
      symptoms declined steadily. Patient diaries documented significant reductions in
      school absences due to sickness. Agalsidase beta was generally well tolerated;
      most treatment-related adverse events were mild or moderate infusion-associated
      reactions involving rigors, fever, or rhinitis. CONCLUSIONS: Agalsidase beta
      safely and effectively reduced the GL-3 accumulation in dermal endothelium
      already evident in children with Fabry disease. Early intervention may prevent
      irreversible end-organ damage from chronic GL-3 deposition.

PMID- 18346517
TI  - Bisphosphonate treatment in chronic recurrent multifocal osteomyelitis.
AB  - OBJECTIVE: To test the safety and efficacy of biphosphonates in chronic recurrent
      multifocal osteomyelitis (CRMO). STUDY DESIGN: Five patients with CRMO, all of
      whom had ongoing pain and loss of function despite conventional treatment with
      non-steroidal anti-inflammatory agents, were treated with pamidronate (1
      mg/kg/dose with a dosing frequency of 2 to 4 monthly for a total treatment
      duration of 12 to 42 months). RESULTS: Pain decreased after the first infusion
      for 4 of 5 patients, with symptomatic improvement maintained with time.
      Significant improvement was seen in radiological lesions for these 4 patients.
      CONCLUSION: Bisphosphonates appear to be a useful and safe adjunctive treatment
      in CRMO when simple therapies such as anti-inflammatory agents fail to control
      symptoms or cases in which lesion expansion continues.

PMID- 18346518
TI  - Comida en venta: after-school advertising on Spanish-language television in the
      United States.
AB  - OBJECTIVE: To analyze the content of food and drink commercials aired during
      after-school hours on Spanish-language television. STUDY DESIGN: We performed a
      content analysis of food and drink advertisements, evaluating product type, food
      category, and message content. All advertisements aired during after-school hours
      (3 to 9 p.m.) on 2 U.S. Spanish-language television stations were sampled over a
      1-week period in the spring of 2006. RESULTS: We reviewed 60 hours of
      programming. Of the non-program content, 47% was for product advertisements, 15%
      (n = 153) of which was for food/drink. A mean of 2.5 food/drink commercials aired
      per hour (range 0-8), and the median duration was 30 seconds; 31% of food/drink
      commercials advertised fast food, and 27% advertised drinks, most (54%) of which
      were sugared. About one third (31%) of the food/drink commercials targeted
      children, 12% featured Latino celebrities, and 19% made reference to Latino
      culture. Only 16% of the food/drink commercials had health-related content.
      CONCLUSIONS: Children viewing Spanish-language television in the United States
      after school are exposed to food and drink commercials, most of which advertise
      unhealthy foods, including fast food and sugared drinks. Food and beverage
      advertising on Spanish-language television may play an important role in the high
      risk of overweight among Latino children.

PMID- 18346519
TI  - Decreased bone mineral density with off-label use of tenofovir in children and
      adolescents infected with human immunodeficiency virus.
AB  - 5 of 6 children infected with human immunodeficiency virus (HIV) receiving
      Tenofovir disoproxil fumarate (TDF) experienced absolute decreases in bone
      mineral density (BMD). 2 pre-pubertal subjects experienced >6% BMD decreases. 1
      subject was the smallest child and experienced a 27% decrease, necessitating
      withdrawal of TDF. Subsequently, her BMD recovered. Monitoring of children
      infected with HIV who require treatment with TDF is warranted.

PMID- 18346520
TI  - Performance of QuantiFERON-TB testing in a tuberculosis outbreak at a primary
      school.
AB  - This study compared the effectiveness of the QuantiFERON-TB Gold (QFT) assay with
      the Mantoux tuberculin skin test to detect Mycobacterium tuberculosis infection
      in 29 children during a school outbreak of tuberculosis. Of the 21 children with
      M. tuberculosis infection, 11 had a radiograph suggestive of the infection. The
      QFT assay was positive in all 21 of the children, and the Mantoux test was
      negative at first testing in 2 children (1 of whom was the sentinel case). The
      findings demonstrate that the QFT test is extremely useful in accurately
      identifying infected and uninfected children, permitting rapid intervention.

PMID- 18346521
TI  - Lymphatic dysplasias in newborns and children: the role of lymphoscintigraphy.
AB  - We performed lymphoscintigraphy in 15 patients (newborns and children) affected
      by congenital lymphatic dysplasia. We suggest that lymphoscintigraphy is
      mandatory in all patients with signs of lymphatic dysplasia, including those with
      minimal and initial signs of lymphatic impairment, to obtain very early diagnosis
      and begin treatment.

PMID- 18346522
TI  - Traumatic brain injury is a rarely reported cause of growth hormone deficiency.
AB  - We determined the frequency of traumatic brain injury (TBI)-related growth
      hormone deficiency (GHD) from a large registry of growth hormone-deficient
      subjects and compared these subjects' clinical characteristics with those of
      children with idiopathic growth hormone deficiency (IGHD). A surprisingly small
      number of subjects with TBI-induced GHD (n = 141) were registered compared with
      those with IGHD (n = 23,722). At onset of treatment, the subjects with TBI
      induced GHD were older (P = .045), had lower height velocity (P < .001), had a
      greater number of other pituitary hormone deficiencies (P < .001) and, after a
      year of recombinant human GH treatment, demonstrated a greater change in height
      velocity (P = .016). We speculate that TBI-induced GHD may be a neglected
      phenomenon in childhood, and recommend prospective longitudinal studies to
      explore its natural history and frequency.

PMID- 18346523
TI  - Ankyloblepharon filiforme adnatum.

PMID- 18346524
TI  - Changes in hemodynamics after closure of the ductus arteriosus in preterm
      infants.

PMID- 18346526
TI  - C-reactive protein and blood pressure in infants.

PMID- 18346527
TI  - Loving corals to death?

PMID- 18346528
TI  - Optimizing outcomes for patients with advanced disease in chronic myelogenous
      leukemia.
AB  - The treatment of chronic myelogenous leukemia (CML) has been revolutionized by
      the development of the small-molecule tyrosine kinase inhibitor imatinib. The
      primary target for this drug is the oncogenic BCR-ABL kinase. Five-year survival
      rates for patients in chronic phase CML is now greater than 80%. Patients who
      have advanced beyond the chronic phase to the accelerated phase or blast crisis,
      however, have not faired as well. Progression occurs for a variety of reasons,
      including late diagnosis, slow response to imatinib, and the development of
      imatinib-resistant clones. Imatinib resistance has, in part, been addressed with
      the introduction of the new BCR-ABL inhibitors, namely dasatinib and nilotinib.
      These drugs have shown efficacy in CML patients with wild-type BCR-ABL and some
      BCR-ABL mutants that are imatinib-resistant. Unfortunately, some BCR-ABL
      mutations remain resistant to these therapies and will require the development of
      alternative treatments, and other mechanisms of imatinib resistance besides BCR
      ABL mutation exist. In the future, genetic and pharmacologic tests may allow the
      clinician to predict response to imatinib. More aggressive therapies are being
      considered for high-risk patients, including increased dosage of the current
      tyrosine kinase inhibitors, along with combination therapies. Aggressive therapy
      holds promise, as the data suggest that responses are improved. Unfortunately,
      toxicities are also increased, and thus a balance must be found to ensure safety
      and compliance. This is especially important for young CML patients, who
      hopefully will remain in remission for decades. Polymerase chain reaction
      analysis has become of primary importance as a means of assessing disease burden,
      and given the idiosyncrasies of this technique, standards must be established to
      allow results to be compared across different institutions. Additionally, the
      nature of advanced disease is being explored. Intriguingly, genetic analysis of
      transformed blasts from patients in blast crisis has identified numerous members
      of the Wnt/B-catenin pathway and JunB as being activated. Increased activity of
      these pathways correlates with poor response and eventual disease progression. In
      addition to these data, evidence is emerging associating survival of the
      quiescent blast cell with Wnt activity, leading to the hope that Wnt inhibitors
      will increase the likelihood of eradicating these cells. Other areas such as
      microRNA profiling and DNA methylation patterns are likely to provide important
      information.

PMID- 18346529
TI  - Neonatal necrotizing enterocolitis. Introduction.

PMID- 18346530
TI  - Necrotizing enterocolitis: recent scientific advances in pathophysiology and
      prevention.
AB  - Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality
      among infants in the neonatal intensive care unit. Here we review the
      epidemiology and pathophysiology of NEC, with an emphasis on the latest research
      findings and potential areas for future research. NEC continues to be one of the
      most devastating and unpredictable diseases affecting premature infants. Despite
      decades of research, the pathogenesis of this disease remains unclear, and
      prevention and treatment strategies are limited. Hopefully, future studies aimed
      at understanding premature intestinal defenses, commensal or probiotic bacterial
      influences, and possible genetic predisposition will lead to the improvement of
      prevention and treatment strategies.

PMID- 18346531
TI  - The neonatal intestinal vasculature: contributing factors to necrotizing
      enterocolitis.
AB  - Based on the demonstration of coagulation necrosis, it is clear that intestinal
      ischemia plays a role in the pathogenesis of necrotizing enterocolitis (NEC).
      Intestinal vascular resistance is determined by a dynamic balance between
      vasoconstrictive and vasodilatory inputs. In the newborn, this balance heavily
      favors vasodilation secondary to the copious production of endothelium-derived
      nitric oxide (NO), a circumstance which serves to ensure adequate blood flow and
      thus oxygen delivery to the rapidly growing intestine. Endothelial cell injury
      could shift this balance in favor of endothelin (ET)-1-mediated vasoconstriction,
      leading to intestinal ischemia and tissue injury. Evidence obtained from animal
      models and from human tissue collected from infants with NEC implicates NO and ET
      1 dysregulation in the pathogenesis of NEC. Strategies focused on maintaining the
      delicate balance favoring vasodilation in the newborn intestinal circulation may
      prove to be useful in the prevention and treatment of NEC.

PMID- 18346532
TI  - The role of nitric oxide in intestinal epithelial injury and restitution in
      neonatal necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the most common life-threatening
      gastrointestinal disease encountered in the premature infant. Although the
      inciting events leading to NEC remain elusive, various risk factors, including
      prematurity, hypoxemia, formula feeding, and intestinal ischemia, have been
      implicated in the pathogenesis of NEC. Data from our laboratory and others
      suggest that NEC evolves from disruption of the intestinal epithelial barrier, as
      a result of a combination of local and systemic insults. We postulate that nitric
      oxide (NO), an important second messenger and inflammatory mediator, plays a key
      role in intestinal barrier failure seen in NEC. Nitric oxide and its reactive
      nitrogen derivative, peroxynitrite, may affect gut barrier permeability by
      inducing enterocyte apoptosis (programmed cell death) and necrosis, or by
      altering tight junctions or gap junctions that normally play a key role in
      maintaining epithelial monolayer integrity. Intrinsic mechanisms that serve to
      restore monolayer integrity following epithelial injury include enterocyte
      proliferation, epithelial restitution via enterocyte migration, and re
      establishment of cell contacts. This review focuses on the biology of NO and the
      mechanisms by which it promotes epithelial injury while concurrently disrupting
      the intrinsic repair mechanisms.

PMID- 18346533
TI  - The importance of pro-inflammatory signaling in neonatal necrotizing
      enterocolitis.
AB  - Despite modern medical advances, necrotizing enterocolitis (NEC) remains a
      significant cause of morbidity and mortality in neonatal intensive care units,
      affecting 10% of premature neonates born weighing less than 1500 g. Although many
      advances have been made in the understanding of NEC, the etiology and
      pathophysiology remain incompletely understood, and treatment is limited to
      supportive care. In recent years, many studies have evaluated the inflammatory
      cascade that is central to the disease process, and research is ongoing into
      strategies to prevent and/or ameliorate neonatal NEC. In this review, we examine
      the key points in the signaling pathways involved in NEC, and potential
      strategies for prevention and treatment of this dreaded disease.

PMID- 18346534
TI  - Role of epidermal growth factor and other growth factors in the prevention of
      necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) presents as the most common gastrointestinal
      emergency during the neonatal period and results in ulceration and necrosis of
      the distal small intestine and proximal colon. The etiology of NEC remains
      unknown. Based on the complexity of gut development, multiple growth factors and
      cytokines may be needed to synergistically support the developing gut. Epidermal
      growth factor (EGF) has been shown to play an important role in intestinal cell
      restitution, proliferation, and maturation. EGF is found in abundant quantities
      in many fluids, including the gastrointestinal tract, amniotic fluid, breast
      milk, and saliva. Preliminary clinical trials using EGF in neonates diagnosed
      with NEC have been shown to promote repair of intestinal epithelium.
      Additionally, other growth factors are also emerging as potential treatment
      modalities, including erythropoietin, granulocyte colony stimulating factor, and
      heparin-binding EGF. The role of EGF and other growth factors in the pathogenesis
      and prevention of NEC will be reviewed.

PMID- 18346536
TI  - Surgical management of necrotizing enterocolitis and isolated intestinal
      perforation in premature neonates.
AB  - Necrotizing enterocolitis (NEC) and isolated intestinal perforation (IP) are two
      relatively common disease conditions that require neonatal surgical therapy. The
      early mortality rate approaches 50%, and survivors frequently have growth and
      neurodevelopmental impairment. Much discussion has occurred regarding whether
      initial drain placement alone or laparotomy with resection of diseased intestine
      should be the initial surgical therapy. Several recent prospective studies have
      shown that the early mortality rate is likely not significantly different after
      either of these surgical approaches. Major morbidity, especially the likelihood
      for neurodevelopmental impairment, may be different in the two treatment groups.
      Further prospective trials are needed to further explore this question and are
      planned. Studies focusing on prevention of NEC and IP and also on improved
      medical treatment are needed to allow a major advance in the outcomes of infants
      with NEC and IP. As these studies are being performed, trials evaluating existing
      medical and surgical therapies are also needed.

PMID- 18346535
TI  - Does abnormal bile acid metabolism contribute to NEC?
AB  - Bile acids (BAs) facilitate emulsification, absorption, and transport of fats and
      sterols in the intestine and liver and are essential for normal digestion.
      However, accumulation of BAs in the intestine can result in damage to the
      intestinal epithelium. Using the neonatal rat model of necrotizing enterocolitis
      (NEC), we have recently shown that BAs accumulate in both the ileal lumen and
      enterocytes of neonatal rats with NEC and the increased BA levels are positively
      correlated with disease severity. Importantly, when BAs are not allowed to
      accumulate, neonatal rat pups develop significantly less disease. In addition, BA
      transporters are altered during disease development. These data indicate that BAs
      play an important role in the development of experimental NEC, and suggest that
      the inability of neonatal rats to adequately regulate BA transporters may be a
      mechanism by which ileal damage occurs.

PMID- 18346537
TI  - Probiotics: role in pathophysiology and prevention in necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is an inflammatory bowel disease largely
      affecting low birth weight, premature infants. Once acquired, NEC is accompanied
      by significant mortality and morbid sequelae. Our understanding of the
      pathophysiology of NEC continues to evolve, and the development of NEC is likely
      multifactorial with resultant bowel injury mediated through a final, common
      inflammatory pathway. The predisposition for NEC appears to involve the interplay
      between intestinal integrity and function, enteral feeding and bacterial
      colonization, and regulation of the gastrointestinal and systemic inflammatory
      response. Commensal organisms or probiotics have been shown to be crucial in the
      development and modulation of each of these factors within the intestinal
      epithelium. As a result, probiotic supplementation has been proposed as a
      promising new intervention for the prevention of NEC. To understand the potential
      utility of probiotics in NEC, we will discuss: the components of gut defense; the
      role of the intestinal ecosystem in modulating immunity and inflammation;
      bacterial colonization patterns in the preterm infant compared with patterns seen
      in the healthy, full-term infant; the evidence for probiotic use in other
      populations and diseases; and finally, the evidence of probiotic use specific to
      the preterm infant and NEC.

PMID- 18346538
TI  - Foot and ankle injuries in dance. Foreword.

PMID- 18346539
TI  - Foot and ankle injuries in dance. Preface.

PMID- 18346540
TI  - Ankle sprains and instability in dancers.
AB  - Ankle inversion injuries are the most common traumatic injuries in dancers. Ankle
      stability is integral to normal mobilization and to minimizing the risk for ankle
      sprain. The ability of the dynamic and static stabilizers of the ankle joint to
      maintain their structural integrity is a major component of the normal gait
      cycle. In the world of dance, this quality assumes even greater importance given
      the range of movement and stresses imposed on the ankle during various dance
      routines.

PMID- 18346541
TI  - Posterior ankle pain in dancers.
AB  - Treatment of dancers can be as challenging as it is rewarding. Dancers often have
      unusual difficulties related to the altered kinesiology required by their
      individual dance form. A thorough understanding of these movements helps guide
      the physician to the cause of the disability, particularly in the setting of
      overuse injuries. This knowledge, coupled with a careful physical examination, is
      essential for the accurate diagnosis and treatment of the dancer, who is both
      artist and athlete.

PMID- 18346542
TI  - Tendon injuries in dance.
AB  - Professional ballet dancers require an extraordinary anatomic, physiologic, and
      psychologic makeup to achieve and sustain their level of ability and activity.
      They are subject to a myriad of injuries as a result of the extreme demands of
      this profession. Tendon injuries are common and often coexist with other
      pathologies of the bone, ligaments, and psyche. It is critical that the dance
      doctor not examine the tendon injury in isolation, but rather the cause of the
      injury, either intrinsic from anatomic malalignment or from external sources,
      including poor form.

PMID- 18346543
TI  - Posterior tibial tendon tears in dancers.
AB  - Posterior tibial tendon tears in dancers are uncommon. No case series of such
      injuries has been presented. The injury does however occur, and should be
      differentiated from the more common causes of medial hindfoot symptoms in
      dancers. The relevant anatomy, biomechanics, and differential diagnosis are
      presented followed by a summary of four cases.

PMID- 18346544
TI  - Foot and ankle fractures in dancers.
AB  - Fractures in the dance population are common. Radiography, CT, MRI, and bone scan
      should be used as necessary to arrive at the correct diagnosis after meticulous
      physical examination. Treatment should address the fracture itself and any
      surrounding problems such as nutritional/hormonal issues and training/performance
      techniques and regimens. Compliance issues in this population are a concern, so
      treatment strategies should be tailored accordingly. Stress fractures in
      particular can present difficulties to the treating physician and may require
      prolonged treatment periods. This article addresses stress fractures of the
      fibula, calcaneus, navicular, and second metatarsal; fractures of the fifth
      metatarsal, sesamoids, and phalanges; and dislocation of toes.

PMID- 18346545
TI  - Forefoot injuries in dancers.
AB  - Dancers, particularly ballet dancers, are artists and athletes. In dance, the
      choreographer acts as a sculptor, using the dancer as a medium of expression.
      This often entails placing the dancer's body in positions that require
      extraordinary flexibility and movement, which requires controlled power and
      endurance. Ballet and other forms of dance can be highly demanding activities,
      with a lifetime injury incidence of up to 90%. Ballet is stressful particularly
      on the dancer's forefoot. The en pointe position of maximal plantarflexion
      through the forefoot, midfoot, and hindfoot requires tremendous flexibility and
      strength that only can be attained safely through many years of training. The
      forces experienced by the toes and metatarsals are extraordinary.

PMID- 18346546
TI  - Bunions in dancers.
AB  - Although dancers put a great deal of stress through the first metatarsophalangeal
      joint (MTPJ), it is unlikely that dancing causes bunions; however, such forces
      may produce an environment in which bunions may develop. It is best to employ
      conservative measures rather than surgical intervention in dancers who have a
      painful bunion. Any surgery on the first MTPJ will adversely affect dorsiflexion
      of this joint, which is a critical motion for dancers. Two types of bunions
      (slowly progressive and rapidly progressive) are commonly seen; arthritic bunions
      occur in dancers who have mild arthrosis and loss of cartilage on the head of the
      first MTPJ. Secondary problems arising from bunions include metatarsalgia, stress
      fractures, sesamoiditis, and flexor hallucis longus tendonitis.

PMID- 18346547
TI  - Nerve disorders in dancers.
AB  - Dancers are required to perform at the extreme of physiologic and functional
      limits. Under such conditions, peripheral nerves are prone to compression.
      Entrapment neuropathies in dance can be related to the sciatic nerve or from a
      radiculopathy related to posture or a hyperlordosis. The most reproducible and
      reliable method of diagnosis is a careful history and clinical examination. This
      article reviews several nerve disorders encountered in dancers, including
      interdigital neuromas, tarsal tunnel syndrome, medial hallucal nerve compression,
      anterior tarsal tunnel syndrome, superficial and deep peroneal nerve entrapment,
      and sural nerve entrapment.

PMID- 18346549
TI  - international dermatology. Preface.

PMID- 18346550
TI  - International dermatology: the many faces and challenges of the specialty in the
      global village.
AB  - The technical advances of the last century changed the understanding of the
      science of cutaneous physiology and pathology and the role of the dermatologist.
      The major challenges the international dermatologic community faces today are the
      lack of a common, logical, and accepted language within the specialty; long
      accepted but questionable policies to advance academic careers; and the
      marginalization of dermatology. Methods for communicating and circulating data
      and ideas also have changed radically. The distribution of knowledge and
      essential/practical tools in different regions of the world is inequitable, and
      developing countries must cope with the challenges of high-impact skin diseases.

PMID- 18346551
TI  - Syphilis: the international challenge of the great imitator.
AB  - Syphilis is a systemic disease caused by the spirochete Treponema pallidum. The
      name of this ancient but pervasive infection is proverbial to health care
      providers. The worldwide recognition of this term, however, argues with the
      intricacy of the disease in addition to the diagnostic and therapeutic challenges
      that persistently affect the global control of syphilis up to the present. This
      article focuses on the varied presentations of the infection, earning the title
      the "great imitator." The article also tackles other significant concerns
      regarding this malady.

PMID- 18346552
TI  - International exchange programs in dermatology: a prescription for the present, a
      hope for the future.
AB  - Little has been written about the various types and availability of international
      exchange programs in dermatology. These opportunities comprise medical student
      electives, mentorships for dermatology residents, international residencies, and
      clinical and research fellowships. For qualified dermatologists, there are
      opportunities for teaching and volunteering in emerging countries and career
      development visiting fellowships to academic centers and private practices to
      learn specific techniques or to focus on particular areas. Exchange programs in
      dermatology, although minimal now, soon may be accessible to most dermatologists
      worldwide, thereby promoting the advancement of scientific and clinical
      dermatologic information. The tables summarize funding sources for these
      exchanges.

PMID- 18346553
TI  - Noncompliance with the world health organization-multidrug therapy among leprosy
      patients in Cebu, Philippines: its causes and implications on the leprosy control
      program.
AB  - The success of current World Health Organization (WHO) key strategy for leprosy
      elimination (ie, multidrug therapy [MDT] regimen) depends largely on the
      efficiency of health care delivery services and patient compliance. A high rate
      of noncompliance with this regimen has serious implications for the leprosy
      control program because it can set the stage for the emergence of drug
      resistance, eventually resulting in treatment failure and failure of the program.
      A community-based descriptive study using pretested interviews conducted in 12
      leprosy endemic areas in Cebu, Philippines, showed that the noncompliance rate
      with the WHO-MDT regimen among 233 study subjects was 30%. The causes of
      noncompliance are drug-related, health care provider-triggered, or patient
      inducted, or some combination of these. Recommendations on strategic
      interventions to obviate the cause for noncompliance are presented.

PMID- 18346554
TI  - Dermatovenereology in the post-communist era: syphilis in Prague during 1999 to
      2005.
AB  - This article presents a retrospective case-note review of patients diagnosed and
      hospitalized with acquired syphilis between January 1999 and December 2005
      performed at the two Departments of Dermatovenereology in Prague. The syphilis
      epidemic in the Czech Republic between 1994 and 2001 now seems to be declining.
      The high rates of immigration from Eastern Europe, unprotected sex, and
      prostitution provide the basis for an epidemic of sexually transmitted
      infections. Early identification of infected individuals and high-risk population
      groups, adequate treatment, partner notification, and treatment of infected
      partners therefore is essential.

PMID- 18346555
TI  - Conversion disorder: "an adverse reaction" to watch out for.
AB  - A subject was enrolled in a multicenter, double-blinded clinical trial of
      ofloxacin-containing multidrug therapy for leprosy by the World Health
      Organization in 1992 and she developed multiple physical symptoms a few hours
      after taking the regimen. Physical examination and laboratory work-ups could not
      support a medical diagnosis and she was eventually dropped from the study.
      Decoding revealed that she belonged in the control group given the World Health
      Organization/multiple drug therapy-multibacillary regimen. In the course of
      treatment, she was diagnosed with conversion disorder and was subsequently
      treated with an antipsychotic.

PMID- 18346556
TI  - Poverty, dignity, and forgotten skin care: dermatology in the stream of human
      mobile population.
AB  - Skin diseases represent the greatest public health care problem in all developing
      countries. Tropical diseases tend to cluster in poor populations and often are
      defined as "neglected" because the investments made to combat them seem
      negligible compared with the massive amounts expended globally on the health
      problems of developed countries. After reviewing the worldwide situation, this
      article explains the principles of community dermatology and discusses the work
      of the San Gallicano Institute in Rome, which has developed a model for reducing
      the number of people suffering from dermatologic and other diseases and has
      established the first dermatologic hospital in Ethiopia.

PMID- 18346557
TI  - Paracoccidioidomycosis.
AB  - Paracoccidioidomycosis is a fungal infection that is relatively common in Brazil,
      Venezuela, Colombia, Ecuador, and Argentina. Sporadic cases can also be seen in
      some other countries. It is caused by a dimorphic fungus, Paracoccidioides
      brasiliensis, which affects mainly the skin, lymph nodes, lungs, and oral, nasal,
      and gastrointestinal mucous membranes. Depending on the specific immunity of the
      host, the infection can assume many forms and affect single or multiple organs,
      eventually becoming a severe and even fatal disease. It is very important for
      dermatologists of all over the world to know about paracoccidioidomycosis because
      sometimes the disease only manifests many years after the individual has left the
      endemic area.

PMID- 18346558
TI  - Nondermatophytic filamentous fungi infection in South America--reality or
      misdiagnosis?
AB  - For the last 10 years, a steady increment in the diagnosis of nondermatophyte
      filamentous fungal infections has been observed. This trend also applies to the
      valuation of the medical mycology. It can be attributed, in part, to the
      increased concern of the population with the aesthetic aspect, the easiest access
      to health information, and the increased demand for specialized jobs. Moreover,
      increase in the diagnosis of new emerging fungi is also caused by the improvement
      of the diagnostic techniques available as well as the qualification and constant
      update of the professionals in medical mycology. Another relevant aspect is the
      valorization of medical mycology in the medical curriculum. Misdiagnosis can lead
      to treatment failures, because not all nail diseases are caused by fungi.
      Therefore, the importance of clinical diagnosis is strictly associated with
      laboratory results.

PMID- 18346559
TI  - Skin tuberculosis in children: learning from India.
AB  - Cutaneous tuberculosis in children is a major health problem in India. It
      accounts for about 1.5% of all the cases of extrapulmonary tuberculosis.
      Scrofuloderma and lupus vulgaris are the two most common forms of tuberculosis.
      However, the trend in the pattern of cutaneous tuberculosis is changing, as the
      tuberculid, lichen scrofulosorum, has become more common in recent years.
      Overall, the clinical patterns are comparable with adults. However, children can
      have widespread and severe involvement because many unusual and uncommon patterns
      are known to occur in children. Underlying systemic involvement is more common in
      children, compared with adults.

PMID- 18346560
TI  - Teledermatology: how to start a new teaching and diagnostic era in medicine.
AB  - "Telemedicine" is defined as the use of telecommunication technologies for the
      exchange of medical information across distances. Applications include patient
      management as well as research and education. Teledermatology is a steadily
      growing category of telemedicine. This article presents general aspects of
      telemedicine, such as modes of data transmission, and practical applications with
      a special emphasis on their significance for teledermatology.

PMID- 18346561
TI  - Internet addiction: recognition and interventions.

PMID- 18346562
TI  - A narrative framework for understanding experiences of people with severe mental
      illnesses.
AB  - This article discusses the value of a narrative approach to understand the
      experiences of people with severe mental illnesses and the systems around them,
      and the importance of narrative in the patient-practitioner relationship. These
      are important concepts in the shift to recovery-oriented systems. People lead
      storied lives which provide coherence and meaning, but that story has the
      potential to be change. Both consumers and practitioners have stories, and it is
      the shared decision-making between them that can lead to recovery. Narratives can
      be illness narratives, initiated by an illness and the search for meaning in it,
      or counterstories which are inherently political. The article identifies a
      Framework for Understanding Stories as a means for listening to and understanding
      stories at multiple levels. It can be useful for nurses to understand complexity
      and multilevel aspects of an individual's experience. Although people tell their
      own individual stories, they compose them by adapting narrative types, which a
      culture makes available. Programs tells a story and provide an important context
      for both consumers and practitioners. Dominant societal narratives provide an
      overall context which can be empowering or disempowering for programs, consumers
      and practitioners. Thus, as the recovery paradigm has become more prominent,
      people with mental illnesses have increasingly talked and written about recovery.

PMID- 18346563
TI  - Hope from the perspective of people with schizophrenia (Korea).
AB  - Studies about hope, a major contributing factor to recovery, are relatively rare
      in mental health literature. This qualitative study was conducted to explore the
      nature of hope in 25 Koreans with schizophrenia (16 men and 9 women).
      Participants were asked to respond to three questions about hope: What does hope
      mean to you? What do you hope for? Where does hope come from for you? Hope in
      people with schizophrenia is similar to hope in people without schizophrenia;
      hope comes from loving and being loved in interpersonal relationships.

PMID- 18346564
TI  - Improving substance abuse screening and intervention in a primary care clinic.
AB  - Despite recent efforts to educate primary care providers in the identification
      and management of patients presenting with substance abuse problems, many
      opportunities to identify and intervene with these patients are overlooked. This
      project was designed to identify factors that interfere with rates of screening
      and brief intervention (SBI) of substance abuse problems in a primary care clinic
      in a major academic medical center in New York City. Six informants representing
      the disciplines of medicine, nursing, and social work in the primary care clinic
      provided information regarding SBI. Analysis was focused on substantiation of the
      need for enhanced diffusion of knowledge related to screening for substance abuse
      problems to improve rates of SBI in primary care. Recommendations for improvement
      included continued promotion of SBI by influential role models and opinion
      leaders, improvement in primary care providers' perceptions of the perceived
      characteristics of SBI to improve rates of adoption, implementation of
      interdisciplinary educational initiatives toward the goal of improving rates of
      SBI in the primary care clinic, and initiation of translational research at the
      clinic supporting SBI in primary care.

PMID- 18346565
TI  - Comparing the efficiency of eight-session versus four-session memory intervention
      for older adults.
AB  - Evidence that reduced treatment achieves similar outcomes is beneficial because
      shorter interventions may be more cost-effective and more acceptable to
      participants. We examined the effects of shortening a memory intervention for
      elders from eight sessions to four sessions. Shortening the intervention had
      little impact on either self-reported or performance measures of memory and daily
      living activities. Small to moderate effects were associated with positive
      changes in both groups. When examining cost-effectiveness, an eight-session
      intervention produced slightly greater gains in memory performance, but at a
      higher cost. Future studies should systematically vary key intervention
      components in more diverse samples.

PMID- 18346566
TI  - Measuring adverse outcomes in inpatient psychiatry: the reliability of nurse
      recall.
AB  - Nurses have been used in studies to report on quality-of-care issues and may be
      the most feasible sources of information about adverse outcomes. To date,
      however, the use of nurses to recall adverse outcomes of inpatient psychiatric
      care has not been examined systematically. The purpose of this study was to
      determine the reliability of psychiatric nurses' recall of physical restraint
      episode(s) (PRE) and assaultive/aggressive episode(s) (A/AE) and to describe the
      factors that influence recall. The study design was prospective and
      retrospective, and used a convenience sample of 36 nurses from a psychiatric
      hospital located in a large eastern city. Despite differences in nurse
      characteristics, perceptions of shift conditions, and organizational
      characteristics, nurse recall of PRE and A/AE was reliable overall. The majority
      of nurses actually recalled the exact number of events they had prospectively
      reported. Furthermore, the period for recall (2 vs. 4 weeks) did not
      significantly affect the reliability of nurse recall. These results suggest that
      psychiatric nurses are reliable informants of adverse outcomes. Lacking readily
      accessible and systematically reported data on PRE and A/AE, nurses may be the
      most feasible sources of information for these outcomes of inpatient psychiatric
      treatment. Future research should replicate these findings in other psychiatric
      treatment settings.

PMID- 18346567
TI  - Depiction of psychiatric nursing in federal reports: the good news and the bad
      news.

PMID- 18346568
TI  - Evaluating Mindfulness-Based Stress Reduction: analyzing stories of stress to
      formulate focus group questions.
AB  - The primary purpose of this analysis was to learn how therapeutic community (TC)
      residents describe Mindfulness-Based Stress Reduction (MBSR) delivered as part of
      their substance use recovery experience. A secondary purpose was to develop focus
      group questions guided by TC residents' descriptions. Two researchers
      independently analyzed 38 written stories about stress in the TC. The researchers
      used conventional content analysis; independent analysis was followed by
      consensus dialogue to identify key words and code definitions. Three themes
      emerged from the content analysis: utility, portability, and sustainability.
      Participants talked about MBSR as a tool which helped them "manage" their
      recovery, noting that they used MBSR techniques in the TC and off-site. They
      believed they could use MBSR even after exiting the TC. Three focus group
      questions were formulated, one for each theme. Content analysis of stories of
      stress provided substantive guidance for formulating focus group questions which
      incorporated the voice of participants through familiar terms and friendly
      language.

PMID- 18346569
TI  - Endovascular repair of a ruptured descending thoracic aortic aneurysm in a
      patient with an ascending aortic aneurysm: hybrid open arch reconstruction with
      simultaneous thoracic stent-graft deployment within elephant trunk.
AB  - Endovascular repair of the thoracic aorta is now widely practiced. The extension
      of this technique to emergent settings is in evolution. Pathology of the
      ascending and transverse aortic arch may preclude thoracic aortic stent grafting
      due to the lack of a proximal seal zone. Several hybrid open/endovascular
      approaches have been described. We recently encountered the difficult case of a
      contained rupture of a 6.8 cm descending thoracic aortic aneurysm in a 60-year
      old patient with aneurysmal degeneration of the ascending and transverse aortic
      arch. This patient was treated with a hybrid approach of open ascending and
      transverse arch reconstruction along with simultaneous stent-graft repair of the
      descending thoracic aorta. The open repair established an excellent proximal
      landing zone by use of the "elephant trunk" technique. This technique also
      allowed direct suture fixation of the stent graft to the arch graft to prevent
      stent-graft migration. This hybrid surgical approach was successful and avoided
      the cumulative morbidity that a left thoracoabdominal approach would have added
      to the sternotomy. Further creative uses of these hybrid techniques will
      undoubtedly serve a larger role in the treatment of thoracic aortic pathology.

PMID- 18346570
TI  - Carotid reconstruction in nonagenarians: is surgery a viable option?
AB  - Because of limited longevity and perceived increased perioperative risk, the
      optimal treatment of significant carotid stenosis in nonagenarians is
      controversial. This study was conducted to evaluate our results in this
      demographic group. A retrospective review was performed of carotid
      endarterectomies (CEAs) done in nonagenarians at Cedars-Sinai Medical Center
      between 1996 and 2006. During this period, a total of 2,038 CEAs were performed
      on patients of all ages. Data abstracted included demographics, patient risk
      factors, indications for surgery, perioperative complications, and survival.
      Fifty-three (2.8%) CEAs were performed as the primary procedure on 49 patients
      aged 90 or greater during the study period. Of these patients, 11 (22.4%) had
      diabetes, 38 (77.5%) had hypertension, and 31 (63.3%) had coronary artery
      disease. Eleven patients (22.4%) had a history of smoking, and there were no
      current smokers. Renal disease was present in three (6.1%) patients, one of whom
      was dialysis-dependent. The median length of stay was 2 days with a range of 1 to
      24 days. Five patients (10.2%) required the intensive care unit following
      surgery. There were no postoperative strokes, and none of the patients had
      suffered ipsilateral stroke during follow-up. One patient (1.8%) had a
      perioperative myocardial infarction. One patient died in the perioperative period
      (1.8%). The 1-month stroke and mortality results did not differ significantly
      from those in patients under the age of 90, 0.3% and 0.4%, respectively (p =
      nonsignificant by Fisher's exact test). Using Kaplan-Meier life-table analysis,
      the 1- and 5-year survival rates were 84 +/- 5% and 33 +/- 9%, respectively. Our
      study demonstrates that in a group of well-selected nonagenarians, CEA is a safe
      procedure with acceptable perioperative morbidity.

PMID- 18346571
TI  - Increased endovascular interventions decrease the rate of lower limb artery
      bypass operations without an increase in major amputation rate.
AB  - Progression of peripheral vascular disease may lead to major amputations. We
      sought to understand whether more frequent endovascular angioplasty and stenting
      in patients with limb-threatening ischemia would affect the number of major
      amputations. We retrospectively reviewed the effects of implementing more
      frequent endovascular intervention for the 4 years 2003-2006 at the Veterans
      Affairs Medical Center in Long Beach, California. During this interval
      angioplasty became the preferred method for the treatment of infrainguinal
      vascular disease. Open bypass procedures were performed for patients with limb
      threatening ischemia and extensive lesions that could not be treated by
      angioplasty. Patients were on average 68 +/- 1 years, and 96% were male. The
      patients were 45% active smokers, with 43% diabetics. There was 0% 30-day
      mortality for both groups over the 4 years. the number of below-the-knee, above
      the-knee, and transmetatarsal amputations for fiscal years 2003, 2004, 2005, and
      2006 were, 42, 50, 62, and 41, respectively. Concurrently, there has been a
      reduction in open femoral to popliteal or trifurcation vessel bypasses with 37,
      43, 28, and 14 procedures for 2003, 2004, 2005, and 2006. Angioplasty and
      stenting increased from 12, 12, 24, to 59 over the same period. Patients who had
      a femoral to distal bypass were more likely to have an amputation than those
      undergoing angioplasty (odds ratio = 4.2, 95% confidence interval 1.6-11.5) for
      those with at least 1 year of follow-up, likely due to these patients having more
      severe disease. Increasing the frequency of angioplasty for infrainguinal
      vascular lesions did not increase the number of major lower extremity amputations
      in our stable patient population.

PMID- 18346572
TI  - Balloon control of the suprahepatic inferior vena cava: a novel technique for
      renal cell carcinoma tumor thrombus.
AB  - Renal cell carcinoma has a tendency to extend via the renal vein into the
      inferior vena cava (IVC), and we describe a novel approach to this situation. A
      64-year-old male presented with metastatic right renal cell carcinoma and tumor
      thrombus extending into the retrohepatic IVC. Preoperative imaging revealed a
      large hemangioma adjacent to the IVC, potentially complicating hepatic
      mobilization. Instead, we used a compliant balloon to occlude the suprahepatic
      IVC, securing the wire in the right hepatic vein. With the infrarenal IVC and
      left renal vein occluded, the thrombus was extracted via a right renal
      venotomy/partial cavotomy with minimal bleeding. Balloon occlusion of the
      suprahepatic IVC offers a safe alternative to surgical control of this vessel in
      difficult situations. In addition, it allows for nephrectomy through a
      conventional, small retroperitoneal incision rather than the extended exposure
      needed for the IVC. Hepatic vein positioning of the wire prevents thrombus
      manipulation during balloon placement.

PMID- 18346573
TI  - Surgical bypass of symptomatic central venous obstruction for arteriovenous
      fistula salvage in hemodialysis patients.
AB  - Venous hypertension due to proximal central venous outflow obstruction coexisting
      with a functioning arteriovenous fistula in the ipsilateral arm presents with a
      complex management problem in hemodialysis patients. Ligation of the
      arteriovenous communication is the simplest procedure to relieve symptoms;
      however, this sacrifices the patient's hemodialysis access, which may be the only
      available access in that patient. Surgical bypass of the occlusion is a potential
      option as it obviates the symptoms of venous hypertension while preserving
      dialysis access. Our objective was to evaluate our experience and outcome with
      dialysis patients undergoing surgical bypass for symptomatic central venous
      obstruction and dialysis access salvage. There were three hemodialysis patients
      with severe venous hypertension secondary to subclavian vein obstruction who had
      functioning ipsilateral arteriovenous fistulae. All underwent cephalic vein (n =
      2) or axillary vein (n = 1) to internal jugular vein bypass of the obstructed
      subclavian segment via an 8-mm polytetrafluoroethylene bridge graft. All patients
      had unsuccessful percutaneous transluminal angioplasty (PTA) attempts prior to
      surgical bypass. In two patients, a wire could not be passed through the
      occlusion; in the third, PTA was only transiently successful despite four
      repeated procedures. All patients had complete resolution of symptoms without
      operative mortality. The bypass grafts remained patent, allowing the
      arteriovenous fistulae to provide functional access for the entire duration of
      follow-up after surgery (3-8 months). Surgical bypass of a central vein
      obstruction relieves the symptoms of venous hypertension and prolongs the use of
      the existing hemodialysis access. This surgical option should be well recognized
      within the dialysis community.

PMID- 18346574
TI  - Hemodialysis-related steal syndrome: predictive factors and response to treatment
      with the distal revascularization-interval ligation procedure.
AB  - Hand ischemia due to steal causes major disability in affected members of the
      hemodialysis population. Between February 2000 and March 2007, 24 patients aged
      37-77 years were identified who developed hand ischemia distal to a hemodialysis
      access and required a distal revascularization-interval ligation (DRIL)
      procedure. Of the 24 patients, 22 (92%) were diabetic, 14 (58%) were women, 7
      (29%) had prosthetic grafts, and 17 (71%) had fistulas, all originating from the
      brachial artery. Duration between the initial dialysis access and the DRIL
      procedures ranged 12 hours to 10 months. Conduits used were saphenous vein in 13
      (54%) cases, cephalic vein in 3 (12%) cases, basilic vein in 5 (21%) cases, and
      prosthetic grafts in 3 (12%) cases. There were no operative deaths. Improved
      blood flow and relief of symptoms were observed in 23 (96%) patients. The
      procedure failed early in one patient who had thrombosis of a prosthetic graft.
      Two patients required digital amputations. At a median follow-up of 50 months, 14
      (58%) patients died using the access requiring the DRIL, 2 (8%) did not require
      dialysis, 3 (12%) were using a new access, and 5 (21%) were still using the
      access that had required the DRIL. In late follow-up, only one DRIL bypass
      required revision and the remainder were patent. One patient developed an
      ischemic hand 5 years after his DRIL procedure despite a patent bypass. The
      development of ischemic steal requiring performance of a DRIL procedure is most
      likely to occur in diabetic patients with dialysis access originating from the
      brachial artery. The procedure is effective in ameliorating symptoms while
      preserving the vascular access. The high long-term mortality rate observed in
      this series underscores the fact that patients requiring a DRIL procedure
      represent a subset of dialysis patients with advanced diabetic vascular disease
      and a limited life expectancy. Despite the effectiveness of the DRIL procedure,
      efforts should be concentrated on prevention of ischemic steal in order to lessen
      the morbidity and expense of this condition in the dialysis population.

PMID- 18346575
TI  - Is there a selection bias in applying endovascular aneurysm repair for rupture?
AB  - Accumulating data suggest that endovascular repair (EVAR) of ruptured abdominal
      aortic aneurysms (RAAAs) leads to reduced mortality, but concern exists that this
      may reflect selection bias. We reviewed our overall rupture experience early
      after our protocol was instituted to explore this question. We instituted a
      defined protocol for RAAA with emphasis on EVAR in July 2002, which included
      device availability (consignment), preoperative training, 24-hr access to our
      surgical endosuite and ability to operate imaging in an emergency, and immediate
      availability of a transbrachial balloon cutdown cart for all cases. Charts of all
      RAAA patients who arrived in the operating room alive since institution of our
      protocol were reviewed. Computed tomographic (CT) scans were re-reviewed to
      assess potentially suitable anatomic candidates. From July 2002 to May 2006, a
      total of 52 RAAAs were treated at our institution: 15 pararenal RAAAs, all
      treated by open repair (PR-OPEN), and 37 infrarenal RAAAs, 20 treated by open
      repair (IR-OPEN) and 17 treated by EVAR (IR-EVAR, 32% of all ruptures). Mortality
      rates in the three groups were 47%, 75%, and 35% (p < 0.02 vs. IR-OPEN),
      respectively. Although mortality was significantly lower in the EVAR group,
      overall mortality was 53% (28/52). On re-review of the operative notes and CT
      scans, it is estimated that more than half of those cases repaired using open
      techniques could have been repaired using EVAR based on anatomic criteria alone.
      The most common reason for open repair was hemodynamic instability
      preoperatively; only a minority of cases were excluded from EVAR based on
      unfavorable anatomy after CT scan review in the emergency room. In conclusion,
      during our early experience EVAR for rupture was associated with significantly
      reduced mortality. However, our overall mortality was no different from
      historical values, and this fact along with the extremely high mortality seen in
      the IR-OPEN group suggest that we are simply selecting patients with the greatest
      chance of survival to undergo EVAR. It also appears that many patients who are
      anatomically suitable for EVAR are undergoing open operation because of
      hemodynamic instability. If EVAR for rupture truly decreases mortality in all
      patients, a much more aggressive attitude toward EVAR may be required to lower
      the overall mortality rate.

PMID- 18346576
TI  - A single-institution experience with the AneuRx Stent Graft for endovascular
      repair of abdominal aortic aneurysm.
AB  - We report our experience of endovascular repair of infrarenal abdominal aortic
      aneurysms (EVAR) using the modular AneuRx Stent Graft System. We retrospectively
      reviewed the outcomes of 113 patients who underwent EVAR with the AneuRx system
      performed at our institution between October 1999 and August 2003. The mean age
      of this group was 72.5 years, with 71% (n = 80) over the age of 70 years and 95%
      (n = 107) males. Aneurysm diameter ranged 4.0-9.0 cm, with 33% (n = 37) >6.0 cm.
      The average duration of late follow-up was 32.6 +/- 24.8 months (median = 37).
      Successful deployment of the modular AneuRx system was noted in all patients.
      There were no immediate operative conversions, deaths within 24 hr of operation,
      or type I or III endoleaks observed at the completion of the procedure. Thirty
      day mortality was 3.5% (n = 4). Acute deployment-related complications occurred
      in 10% (n = 13) of patients and included misdeployment, operative bleeding,
      arterial perforation/dissection, and access site complications. Acute systemic
      complications were present in nine patients, predominantly renal and cardiac
      complications. An endoleak noted at any time occurred in 25% of patients, with
      40% of those requiring a secondary intervention. Two patients suffered late
      aneurysm rupture due to a type I endoleak and graft infection. Kaplan-Meier
      analysis revealed 5-year freedom from secondary intervention of 72.4%; freedom
      from aneurysm-related death of 93.9%; and probability of survival based on all
      cause mortality of 60.1%. Endovascular treatment with the modular AneuRx Stent
      Graft System is safe and effective, producing acceptable rates of disease-free
      survival and mid-term clinical outcome.

PMID- 18346577
TI  - Total laparoscopic aortobifemoral bypass: short- and middle-term results.
AB  - We describe early and mid-term results of total laparoscopic aortofemoral bypass
      (TLAFB). TLAFB was performed in 150 cases of severe aortoiliac occlusive disease.
      Aortic approaches included transperitoneal left retrocolic (n = 86), left
      retrorenal (n = 51), and direct (n = 4); the retroperitoneoscopic approach was
      used in nine cases. The procedure was totally laparoscopic in 145 patients
      (96.6%). Median operative and clamping times were 260 (120-450) and 81 (36-190)
      min, respectively. Thirty-day mortality was 2.7%. Nonlethal systemic, local
      vascular, and local nonvascular complications occurred in 21 (14.3%), seven
      (4.8%), and two (1.3%) patients, respectively. Median return to general diet and
      ambulation were, respectively, days 2 and 3. Median hospital stay was 7 days.
      Follow-up was 25.2 +/- 17.6 months (range 1-60) with 3-year primary and secondary
      actuarial patency rates of 93% and 95.6%, respectively. TLAFB gives early and mid
      term patency rates comparable to open direct repair. Laparoscopy allows faster
      recovery and reduces operative trauma.

PMID- 18346578
TI  - Periprocedural complication rates are equivalent between symptomatic and
      asymptomatic patients undergoing carotid angioplasty and stenting.
AB  - Patients with neurologic symptoms who undergo carotid endarterectomy (CEA) have a
      higher incidence of stroke and death in the perioperative period than those with
      asymptomatic carotid disease. This study examines the outcomes of symptomatic and
      asymptomatic patients undergoing carotid stenting (CAS). From 2002 to 2006, 201
      CAS procedures were performed in 193 patients (117 men, mean age 73 +/- 10
      years), of whom 142 were for asymptomatic (AS) and 59 for symptomatic (S)
      disease. Preoperative neurologic symptoms included recent ipsilateral
      cerebrovascular accident (CVA, 29%), transient ischemic attack (50%), and
      amaurosis fugax (22%). There were 201 carotid stents placed (107 Acculink, 43
      Wallstent, 23 Precise, 21 NexStent, 3 Exponent, 3 Xact, 1 Herculink) and 198
      protection devices used (79 Accunet, 53 EPI Filterwire, 43 PercuSurge, 20
      Angiogard, 3 EmboShield). Mean follow-up was 41 weeks. The groups were matched in
      terms of demographics and comorbidities (carotid artery disease, hypertension,
      hyperlipidemia, diabetes mellitus, peripheral vascular disease, smoking, and
      chronic obstructive pulmonary disease; p = nonsignificant [NS]). There was no
      significant difference in anatomic risk factors (neck irradiation, S 3%, AS 6%;
      prior CEA, S 14%, AS 14%; bovine arch, S 22%, AS 16%; p = NS), and the types of
      embolic protection devices and stents used were similar between groups. The mean
      percentages of preintervention carotid stenosis were equal (S 88%, AS 88%), and
      the technical success rate was 99%. Incidence rates of CVA (S 3.4%, AS 1.4%),
      myocardial infarction (S 1.7%, AS 1.4%), and death (S 0, AS 0.7%) were equivalent
      between groups (p = NS). CAS with cerebral protection can be performed safely in
      both symptomatic and asymptomatic patients. The presence of preoperative
      neurologic symptoms does not significantly increase the risk of adverse events in
      the perioperative period in this study.

PMID- 18346579
TI  - Medial antebrachial cutaneous nerve measurements to diagnose neurogenic thoracic
      outlet syndrome.
AB  - A reliable objective test is still needed to confirm the diagnosis of neurogenic
      thoracic outlet syndrome (NTOS). Over the past 20 years, it has been suggested
      that responses to medial antebrachial cutaneous nerve (MAC) and C8 nerve root
      stimulation could be used for this purpose. Herein, we explore this thesis. A
      clinical diagnosis of NTOS was established in 41 patients, all of whom underwent
      surgical decompression. Preoperatively, all patients were studied with MAC
      sensory neural action potential (SNAP) determinations and C8 nerve root
      stimulation. Controls were 19 asymptomatic, healthy volunteers. MAC sensory
      latency on 79 control sides was 1.5-2.4 msec, while latency in 41 symptomatic
      patients ranged 2.2-2.8 msec. Latency of 2.5 or greater was noted in 30 patients
      (specificity 99%, sensitivity 73%), confirming a diagnosis of NTOS, while the
      remaining 11 (27%) fell into the borderline zone of 2.2-2.4 msec. The latency
      difference between right and left sides in controls was 0-0.2 msec in 17 (89%),
      while in NTOS patients 31 had a difference of 0.3 msec or more (sensitivity 89%,
      specificity 63%). Amplitudes of 10 muV or more occurred in 77 of 79 control
      sides, whereas the amplitude was under 10 muV in 28 patients (specificity 97%,
      sensitivity 68%). Amplitude ratios between right and left sides in controls were
      1.7 or less. Ratios of 2.0 or more were measured in 25 patients (specificity
      100%, sensitivity 61%). Using the four diagnostic criteria (latency over 2.4
      msec, latency difference between sides of 0.3 or more, amplitude under 10 muV,
      and amplitude ratios of 2.0 or more), 40 of the 41 patients had at least one of
      the four diagnostic criteria, 23 patients (56%) had three or four positive
      criteria, and 12 (29%) had two. C8 nerve root stimulation responses were below
      normal (56 M/sec) in 54%. MAC measurement is a fairly reliable technique for
      confirming the diagnosis of NTOS. Latency determination appeared to be a slightly
      more consistent measurement in this study, but amplitude and C8 nerve root
      stimulation were also helpful. A combination of these techniques seems to be the
      most reliable approach.

PMID- 18346580
TI  - Viability of engineered vessels as arterial substitutes.
AB  - The search for vessel substitutes to replace small-/medium-caliber vessels is an
      ongoing concern for vascular surgeons. Engineered vessels were designed for use
      as arterial equivalents and assessed in an in vivo model in dog. Three study
      groups were established: clinical expanded polytetrafluoroethylene (ePTFE;
      control, n = 24), ePTFE seeding with endothelial cells (EC graft, n = 12), and
      ePTFE with a fibroblast matrix seeded with EC (FM+EC graft, n = 12). Grafts were
      subjected to a custom-designed femoral ex vivo circuit and implanted in the
      carotid artery for 60 days. The viability of the prosthetic grafts was evaluated.
      The ex vivo circuit revealed that the presence of a fibroblast matrix induced
      over double the cell retention compared to EC grafts. A significant reduction in
      platelet adhesion in EC grafts was observed. After their in vivo implantation,
      the engineered vessels were more efficient at avoiding occlusion than the
      prosthetic grafts. The FM+EC grafts induced more endothelialization than those
      seeded with ECs alone. Intimal hyperplasia response was reduced in the EC
      substitutes. Significant differences in apoptotic cells emerged between the EC
      and control ePTFE grafts. In conclusion, engineered vessels showed improved
      initial patency over ePTFE grafts. The EC graft was best at combating restenosis,
      a good indicator of the long-term efficiency of the graft.

PMID- 18346581
TI  - Angiogenesis in carotid atherosclerotic lesions is associated with timing of
      ischemic neurological events and presence of computed tomographic cerebral
      infarction in the ipsilateral cerebral hemisphere.
AB  - We studied the association between plaque vascularity, timing of neurological and
      ocular symptoms, and presence of cerebral infarction in the ipsilateral cerebral
      hemisphere on preoperative computed tomographic (CT) scan. Consecutive patients
      undergoing carotid endarterectomy for carotid stenosis were included. All
      patients underwent preoperative noncontrast cerebral CT. Histological sections
      were obtained from carotid endarterectomy specimens and stained with an
      endothelial cell marker (CD34). Microvessel counts were performed in CD34-stained
      sections and verified through computerized image analysis. Associations between
      microvessel density in carotid atherosclerotic plaques, preoperative ipsilateral
      CT evidence of cerebral infarction, and timing of ipsilateral neurological and
      ocular events were assessed. Seventy-three patients underwent carotid
      endarterectomy, of whom 17 were symptomatic within 30 days of carotid
      endarterectomy, 11 were asymptomatic, and a further 45 had a preoperative symptom
      free interval of 31-540 days (median = 56). Eighteen patients (24.6%) had CT
      evidence of cerebral infarction. Significantly higher microvessel counts were
      observed in patients with CT evidence of cerebral infarction in the appropriate
      hemisphere compared with patients who did not (p = 0.02). There was an inverse
      relationship between the microvessel density in atherosclerotic lesions and the
      timing of ischemic neurological events (odds ratio [OR] = 4.63, 95% confidence
      interval [CI] 2.95-7.28, p < 0.001). This relationship was independent of patient
      age (OR = 1.03, 95% CI 0.55-1.99, p = 0.70), sex (OR = 1.18, 95% CI 0.47-2.05, p
      = 0.56), smoking (OR = 1.07, 95% CI 0.54-2.09, p = 0.84), diabetes (OR = 0.90,
      95% CI 0.45-1.79, p = 0.76), and hypercholesterolemia (OR = 0.98, 95% CI 0.68
      1.11, p = 0.88). This study confirms the relationship between angiogenesis in
      carotid atherosclerotic lesions and development and chronology of ipsilateral
      hemispheric neurological events.

PMID- 18346582
TI  - Vascular endothelial growth factor induces extracellular matrix proteins and
      osteopontin in the umbilical artery.
AB  - Vascular endothelial growth factor (VEGF) is a mitogenic, angiogenic, and potent
      mediator of vascular permeability. It plays a role in injuries, contributes to
      edema during the acute stage of tissue damage, and promotes repair during
      recovery. We recently showed that VEGF serum levels of burn patients with a
      considerable number of damaged vessels were significantly increased. Here, we
      study the effects of VEGF on healthy vessels treated with a comparable VEGF
      concentration achieved in patients suffering heavy burns. VEGF 165 (0.2 mL of 10
      ng/mL) or vehicle (saline 0.9%) was intraluminally applied to umbilical arteries
      for 90 min at 37 degrees C. Then, the cord was perfused for 4 hr. During
      perfusion, functional and biochemical parameters were kept within normal
      physiological ranges. Afterward, the vessels were analyzed applying morphometry,
      sirius red staining, polarization microscopy, Western blot analysis, and
      immunohistochemistry. Moreover, cultured human umbilical vein endothelial cells
      (HUVECs) were treated with VEGF or vehicle for 90 min and 5.5 hr to examine
      extracellular matrix (ECM) proteins and receptor tyrosine kinases. VEGF-treated
      umbilical arteries showed significant tissue edema and simultaneously an
      enhancement of laminin and collagen types I, III, and IV compared with control
      arteries. We detected an increase in Flt-1, Flk-1, osteopontin, and ss(1)
      integrin. VEGF induced laminin early in HUVECs as measured by flow cytometry. In
      parallel, VEGF induced a higher amount of osteopontin, ss(1)-integrin, and both
      receptor tyrosine kinases in endothelial cells within 90 min. Intraluminal
      application of VEGF enhances ECM protein, osteopontin, and ss(1)-integrin
      production of the endothelium, while it still generates tissue edema. VEGF
      initiates vascular remodeling as early as it generates edema, even if the target
      vessel is not damaged. Osteopontin and ss(1)-integrin, both induced by VEGF, may
      play an important role in the vascular remodeling process.

PMID- 18346583
TI  - Complex regional pain syndrome: a review.
AB  - Complex regional pain syndrome (CRPS), formerly known as "reflex sympathetic
      dystrophy," is a chronic neurological disorder characterized by disabling pain,
      swelling, vasomotor instability, sudomotor abnormality, and impairment of motor
      function. The disorder usually develops after minor trauma or surgery. No
      specific diagnostic test is available and, hence, diagnosis is based mainly on
      history, clinical examination, and supportive laboratory findings. This review
      gives a synopsis of CRPS and discusses the principles of management based on the
      limited available literature in the area. A literature search was conducted using
      electronic bibliographic databases (Medline, Embase, Pubmed, CENTRAL) from 1970
      to 2006. Keywords complex regional pain syndrome, reflex sympathetic dystrophy,
      neuropathic pain, and causalgia were used for the search. Relevant articles from
      the reference lists in retrieved articles were also studied. There were 3,771
      articles published in the area. Seventy-six randomized controlled trials were
      identified. Most studies were on the role of sympathetic blockade in the
      treatment of CRPS (n = 13). The role of sympathectomy is unclear, with some
      studies showing transient benefit and others showing no beneficial effects, with
      most studies containing only a small number of patients. Nine studies were on
      bisphosphonates or calcitonin. Studies involving bisphosphonates showed benefit,
      but studies involving calcitonin showed no definite benefit. Four studies were on
      cognitive behavioral therapy, physiotherapy, or occupational therapy, all of
      which demonstrated a potential beneficial effect. Three studies on spinal cord
      stimulation and two studies each on acupuncture, vitamin C, and steroid all
      showed a potential beneficial effect in pain reduction. The remaining studies
      were on miscellanous therapy or combination therapy, making it difficult to draw
      any conclusions on the effect of treatment. There is very little good evidence in
      the literature to guide treatment of CRPS. Early recognition and a
      multidisciplinary approach to management seems important in obtaining a good
      outcome. Treatments aimed at pain reduction and rehabilitation of limb function
      form the mainstay of therapy. Comorbidities, such as depression and anxiety,
      should be treated concurrently.

PMID- 18346584
TI  - Ligation of the perforating vein: a treatment for steal syndrome in side-to-side
      elbow arteriovenous fistula.

PMID- 18346585
TI  - Imaging. Foreword.

PMID- 18346586
TI  - Imaging. Preface.

PMID- 18346587
TI  - Analysis of radiographic classifications for rotational ankle fractures.
AB  - The acute ankle fracture has been often cited as one of the most commonly treated
      orthopedic injuries. As such, significant research has been conducted, along with
      many clinical studies, aiming to evaluate conservative versus surgical
      management, as well as radiographic classification and long-term outcomes.
      Because these clinical outcomes are pertinent to practicing physicians, this
      article aims to examine studies that assess the reliability and reproducibility
      of familiar classification systems for rotational ankle fractures.

PMID- 18346588
TI  - Imaging evaluation of distal tibia transitional fractures.
AB  - Transitional fractures are a rare injury to the distal tibia that occur only in
      adolescents because of the asymmetric closure of the physis. These fractures can
      occur in multiple planes and have varying number of fragments, depending on the
      amount of closure that has taken place in the distal tibial physis at the time of
      injury. A thorough evaluation of a suspected transitional fracture requires
      advanced imaging studies for diagnosis, prognosis, and treatment planning.
      Accuracy is paramount in treatment of these injuries to prevent long-term
      complications. This article is a review of the literature on transitional
      fractures, with a case presentation.

PMID- 18346589
TI  - Synovial sarcoma: a case report.
AB  - Synovial sarcoma most commonly affects adults in the third to fifth decades of
      life, and is the most common sarcoma of the foot. The tumors are encapsulated and
      frequently in contact with bone. Because there are often few anatomical barriers,
      malignant spread to surrounding nerves and vasculature is common. This article
      discusses the case of a young patient who presented to the foot and ankle clinic
      with soft tissue swelling in the right foot, and the imaging protocol for such a
      patient. A literature review of synovial sarcoma is also presented.

PMID- 18346590
TI  - Imaging strategies for diagnosing calcaneal and cuboid stress fractures.
AB  - Stress fractures of the calcaneus and cuboid bones are not among the most common
      pathologies seen by the foot and ankle specialist on a day-to-day basis.
      Therefore, the clinician must be suspicious of these particular entities when
      conservative therapy has failed to alleviate the pain of a more common condition.
      The purpose of this article is to discuss the signs, symptoms, MRI findings,
      nuclear imaging characteristics, and radiographic features associated with
      calcaneal and cuboid stress fractures. Case studies of both conditions are also
      discussed within this article.

PMID- 18346591
TI  - Ankle sprain complications: MRI evaluation.
AB  - Sprains are disruptions of the ligamentous anatomy about a joint. The ankle
      sprain is one of the most common injuries seen in podiatric and orthopedic
      practice. It usually is incurred from an inversion force on the ankle, but
      eversion forces also can traumatize the ankle. Many times, this injury is taken
      for granted because of the frequency of its presentation. The patient usually is
      given appropriate initial care, but the patient can experience continued or
      residual pain. Podiatrists have found this problem is common and have come to
      recognize that secondary or accessory injuries occur that slow the natural
      recovery of this injury.

PMID- 18346592
TI  - Foot and ankle imaging in the athlete.
AB  - Foot and ankle injuries are among the most common of all sports-related injuries.
      Many injuries are simplistic from a diagnostic standpoint, whereas others require
      a high level of suspicion and the use of appropriate diagnostic imaging
      modalities. Whether a professional athlete or a weekend warrior, all athletes
      want minimal disruption to their sporting activity and a quick return to
      competition. An accurate diagnosis aids in the development of an appropriate
      rehabilitation program and in return to activity. This article reviews the more
      common foot and ankle injuries seen in the podiatrist's office and the preferred
      imaging modalities used to evaluate them.

PMID- 18346593
TI  - Imaging of the Charcot foot.
AB  - Charcot foot is a serious problem that causes considerable morbidity and may lead
      to limb loss. Arriving at a definitive diagnosis can be challenging. Given the
      progressive, destructive nature of Charcot's arthropathy, this delay can result
      advancing deformity, ulceration, infection, and place the limb at risk for
      amputation. Although clinical signs and symptoms and historical information are
      crucial, this article focuses on the imaging modalities that can aid
      practitioners in arriving at an early diagnosis, and how to differentiate
      Charcot's arthropathy from osteomyelitis of the feet.

PMID- 18346594
TI  - Circular external fixation for the midshaft and distal tibial fractures: a report
      on healing times.
AB  - Circular external fixation for the treatment of any tibio-fibular fracture should
      be taken into consideration as a versatile, minimally invasive technique.
      Patients should be given this option (when indicated) as one of their fixation
      alternatives. The healing times we reported are comparable to IM nailing healing
      times in the mentioned article. Further studies with outcome scores,
      complications, and long-term outcomes are necessary for circular external
      fixation in the treatment of tibial fractures.

PMID- 18346595
TI  - Treatment of displaced intra-articular calcaneal fractures with triangular tube
      to-bar external fixation: long-term clinical follow-up and radiographic analysis.
AB  - Sixty-six feet (62 patients) with displaced intra-articular calcaneal fractures
      underwent manual reduction and distraction with the use of a triangular tube-to
      bar external fixation device and were retrospectively reviewed at a minimum of 1
      year post-operative. Final radiographic follow-up revealed complete consolidation
      in all fractures, maintenance of reduction, and limited degenerative
      osteoarthrosis about the subtalar joint. Our results indicate that with proper
      application and attention to detail, restoration of calcaneal morphology using
      triangular tube-to-bar external fixation should be considered a viable
      alternative in the treatment of displaced intra-articular fractures of the
      calcaneus.

PMID- 18346596
TI  - Physical health considerations in psychiatry: european views on recognition,
      monitoring and management.

PMID- 18346597
TI  - Overcoming hurdles to achieving good physical health in patients treated with
      atypical antipsychotics.
AB  - Hurdles that must be overcome in order to implement guidelines and maximize
      physical health in patients treated with antipsychotics include the impression
      that a disruption in physical health is an inevitable token for the patient to
      pay in order to achieve and maintain his or her mental health; lack of routine
      monitoring; lack of defined care pathways for evaluation, monitoring and
      treatment of physical health issues in psychiatry; the burden of guideline
      implementation on mental health team resources; the difficulty to perform certain
      procedures (e.g. monitoring of waist circumference); and reluctance to switch
      medications once physical health effects are recognized, especially if the
      psychiatric symptoms are under relatively good control. It is imperative that we
      act now to overcome these hurdles and maximize outcomes for our patients.
      Strategies include establishing simple, consistent processes for physical health
      monitoring and tracking in clinical practice; provision of appropriate equipment
      to staff; effective education of all personnel involved in the care of
      psychiatric patients regarding this important topic; and consideration of a
      medication switch in patients whose medication is a high-risk contributory factor
      to poor physical health.

PMID- 18346598
TI  - Prolactin awareness: an essential consideration for physical health in
      schizophrenia.
AB  - Elevations in serum prolactin levels (hyperprolactinaemia) are a common side
      effect of conventional and some atypical antipsychotic treatments. In patients
      with schizophrenia, the adverse effects of antipsychotic-induced
      hyperprolactinaemia on physical health (e.g. fertility problems, sexual
      dysfunction and reduced bone mineral density) are gaining attention. Accumulating
      evidence shows consistent 'prolactin-raising' effects of conventional
      antipsychotics and risperidone compared with other current atypical
      antipsychotics, which are more likely to have 'prolactin-sparing' properties.
      Prolactin-sparing antipsychotics (for example, aripiprazole and quetiapine) tend
      to show lower frequencies of hyperprolactinaemia-associated side effects. In
      recent studies, aripiprazole-treated patients have demonstrated lower prolactin
      levels compared with patients receiving other prolactin-sparing antipsychotics.
      There is a lack of robust recommendations for monitoring prolactin elevation
      among patients receiving antipsychotics. Decreasing the antipsychotic dose or
      switching to a prolactin-sparing medication are possible management options for
      antipsychotic-induced hyperprolactinaemia. There is a need to increase awareness
      and understanding of the impact of antipsychotic-induced hyperprolactinaemia on
      physical health in schizophrenia.

PMID- 18346599
TI  - Psychosocial and economic issues related to physical health in psychiatric
      illness.
AB  - As well as the obvious medical consequences associated with physical health
      problems in individuals with schizophrenia, physical health problems lead to a
      number of psychosocial consequences--further contributing to the existing burden
      of schizophrenia itself. Weight gain can seriously impair quality of life through
      decreased functioning, social stigmatization, discrimination and potential
      financial consequences. However, patients with schizophrenia may be less capable
      of managing their weight via exercise and dietary interventions compared with the
      general population, and may, therefore, be more prone to non-compliance with a
      medication that induces weight gain. This may lead to exacerbation of the mental
      illness. Patients' perceptions and experience of antipsychotic treatments are
      also important as these can further impact on overall patient wellbeing. It is
      hoped that by increasing awareness of the psychosocial consequences of physical
      health impairment, we can move towards reducing the burden that patients face.

PMID- 18346600
TI  - Management of physical health in schizophrenia: a stepping stone to treatment
      success.
AB  - While patients with schizophrenia are known to have an increased risk of physical
      health co-morbidity including coronary heart disease, diabetes, hypertension,
      stroke and emphysema, their physical wellbeing often goes unnoticed by health
      care professionals. In many cases the patient's only contact with the health
      service is through the mental health team. However, many psychiatrists consider
      their primary function to be the provision of clinical care in terms of symptom
      control and are reluctant to switch medication despite the presence of physical
      health issues. Nevertheless outcomes in schizophrenia may be improved by
      expanding the remit of the clinician to include assessments of both physical and
      mental health. Simple measurements such as waist circumference, weight, height,
      blood pressure and blood sampling would provide the psychiatrist with useful
      information that could be used to optimize treatment and improve overall quality
      of life for patients with schizophrenia.

PMID- 18346601
TI  - Perioperative statin intake for coronary artery bypass graft surgery: do
      pleiotropic effects have benefit?

PMID- 18346602
TI  - Preoperative statin intake and morbid events after isolated coronary artery
      bypass grafting.
AB  - STUDY OBJECTIVE: To examine the effect of statins on morbidity and mortality in
      patients after isolated coronary artery bypass grafting (CABG). DESIGN:
      Observational cohort study. SETTING: Tertiary-care teaching hospital.
      MEASUREMENTS: Data from 2497 adult patients who underwent isolated CABG between
      January 2002 and June 2004 were studied. Patient characteristics and
      intraoperative variables were prospectively collected. End points were major
      morbid events and in-hospital mortality. A propensity score was estimated for
      each patient using logistic regression on the probability of statin use. Patients
      were also classified into 5 quintile groups according to their propensity score.
      Outcome variables were compared for propensity-matched pairs and quintile groups
      between those who received and did not receive statin therapy. MAIN RESULTS:
      Propensity matching resulted in a similar distribution of variables among the 654
      matched pairs. Similar perioperative mortality was found between matched pairs
      with statin therapy vs no statin therapy, 5 (0.76%) and 8 (1.2%), (P = 0.40),
      respectively. Cardiac, neurologic, renal and respiratory morbidity, occurrence of
      atrial fibrillation, and length of hospital stay were similar between the matched
      pairs and among quintiles of propensity scores. CONCLUSIONS: Preoperative statin
      intake did not reduce the frequency of major perioperative morbid events after
      isolated CABG.

PMID- 18346603
TI  - Blocking noise but not music lowers bispectral index scores during sedation in
      noisy operating rooms.
AB  - STUDY OBJECTIVE: To determine whether playing music or blocking noise can reduce
      bispectral index (BIS) values during propofol sedation. DESIGN: Prospective,
      randomized, single-blinded study. SETTING: Operating room. PATIENTS: 63 ASA
      physical status I and II patients, aged 55 to 75 years, undergoing total knee
      replacement. INTERVENTIONS: Patients were divided into three groups: noise,
      silence, and music. After induction of combined spinal-epidural anesthesia,
      sedation was begun with 1.2 mug/mL of propofol in a target-controlled infusion.
      In the silence group, patients' ears were packed tightly to block ambient noise,
      whereas patient-selected music was applied to patients in the music group.
      Patients in the noise group were exposed to ambient operating room noise.
      MEASUREMENTS: Bispectral index measurement was recorded 7 times during operation.
      Ambient room noise was recorded at the same time sequence. MAIN RESULTS: Sound
      level was highest when the saw (T3, 80.25 dB) and the impact device (T4, 80.98
      dB) were in use. Bispectral index scores in the silence group during those times
      (T3, 68.5 vs 76.9, P = 0.025, and T4, 67.6 vs 78, P = 0.005) were lower than in
      the noise group. However, BIS scores were similar in the noise and music groups.
      Preoperative anxiety level, postoperative comfort level, and pain scores were
      similar in all groups. CONCLUSION: Blocking noise is more effective than playing
      music in reducing BIS scores during propofol sedation in a noisy environment.

PMID- 18346604
TI  - Epidural analgesia after scoliosis surgery: electrophysiologic and clinical
      assessment of the effects of bupivacaine 0.125% plus morphine versus ropivacaine
      0.2% plus morphine.
AB  - STUDY OBJECTIVE: To study the electrophysiologic and clinical effects of epidural
      morphine combined with either bupivacaine 0.125% or ropivacaine 0.2%. DESIGN:
      Comparative, randomized, double-blind study. SETTINGS: Intensive care unit and
      hospital ward of a university hospital. PATIENTS: 18 adult ASA physical status I
      and II patients with degenerative or idiopathic scoliosis, undergoing posterior
      spinal fusion with instrumentation. INTERVENTIONS: Patients received epidural
      administration of 10-mL bolus of either bupivacaine or ropivacaine followed by a
      6-mL/h infusion for 48 hours of unlabeled local anesthetic. In all patients,
      epidural morphine 5 mg was added daily. MEASUREMENTS: Assessment was focused
      mainly on somatosensory cortical evoked potentials, soleus H-reflex, and F waves.
      These electrophysiologic data were recorded before and after epidural
      medications. Second, respiratory rate, Paco(2), visual analog score (VAS), and
      side effects such as postoperative nausea and vomiting (PONV), gastrointestinal
      (GI) transit delay, and urinary retention were noted. MAIN RESULTS: Bupivacaine
      0.125% + morphine was given to 9 patients, and ropivacaine 0.2% + morphine was
      given to 9 other patients. H-reflex, F waves, and somatosensory cortical evoked
      potential recording remained unchanged across the time of assessment. Respiratory
      rate and Paco(2) values were normal. VASs were indifferently low at rest, but
      they were lower with bupivacaine than with ropivacaine on mobilization. The
      frequency of PONV was indifferently high. No altered GI transit or urinary
      retention was noted. CONCLUSION: After epidural administration during the study
      conditions, bupivacaine 0.125% and ropivacaine 0.2% combined with morphine allow
      for neurologic examination.

PMID- 18346605
TI  - Clinical assessment of propofol-induced yawning with heart rate variability: a
      pilot study.
AB  - STUDY OBJECTIVES: To investigate the proportion of propofol-induced yawning and
      sympathovagal balance during propofol-induced yawning. DESIGN: Prospective,
      observational, clinical study. SETTING: University hospital and 2400-bed tertiary
      medical center. PATIENTS: 546 ASA physical status I and II patients undergoing
      elective surgery with general anesthesia. INTERVENTIONS: Standard induction of
      anesthesia was performed with intravenous (IV) propofol two to four mg/kg (group
      P), or pretreatment with atropine 0.1 mg/kg (group AP) or with fentanyl 1 to 3
      microg/kg (group FP) before propofol. Continuous standard electrocardiogram for
      heart rate variability (HRV) was performed in another 20 patients to investigate
      sympathovagal balance during propofol-induced yawning. MEASUREMENTS AND MAIN
      RESULTS: The proportions of yawning were 53.5% (207/386), 61.1% (55/90), and 0%
      (0/50) in the P, AP, and FP groups, respectively. Propofol-induced yawning could
      be dramatically decreased by pretreatment with IV fentanyl (P < 0.001, chi2
      test). Significant increased ratio of low-frequency/high-frequency power was
      detected during HRV monitoring in 9 patients with yawning in comparison with 11
      patients without yawning (P < 0.05, Wilcoxon signed-rank test). CONCLUSIONS:
      Pretreatment with fentanyl may inhibit propofol-induced yawning. Fluctuations in
      autonomic function have been noted during propofol-induced yawning.

PMID- 18346606
TI  - Effect of preoperative oral erythromycin, erythromycin-ranitidine, and ranitidine
      metoclopramide on gastric fluid pH and volume.
AB  - STUDY OBJECTIVE: To determine whether combining erythromycin with ranitidine is
      more efficacious than erythromycin or established ranitidine-metoclopramide
      combination in reducing the volume and acidity of gastric aspirate. DESIGN:
      Randomized, double-blind study. SETTING: Operating room complex. PATIENTS: Eighty
      ASA physical status I and II patients. INTERVENTION: Patients were divided into 4
      groups of 20 patients each. All patients received the study medication (in tablet
      form) packed in identical gelatin capsules 60 to 90 minutes before surgery in the
      premedication room. Patients in group PP were given two placebo tablets; group EP
      received erythromycin 250 mg, and placebo; group ER received erythromycin 250 mg,
      and ranitidine 150 mg; and group RM was given ranitidine 150 mg, and
      metoclopramide 10 mg. MEASUREMENTS: After tracheal intubation, gastric fluid was
      aspirated via orogastric tube, and volume and pH of the aspirate were studied.
      RESULTS: Significantly higher gastric volume occurred in group PP than groups EP,
      ER, or RM (P < 0.001). There were no differences in volumes among groups EP, ER,
      and RM. Gastric pH was significantly lower (P < 0.001) in groups PP and EP than
      in groups ER and RM. CONCLUSION: Erythromycin and ranitidine combination is more
      efficacious than erythromycin alone in reducing the acidity and volume of gastric
      fluid. No difference was found between erythromycin-ranitidine and ranitidine
      metoclopramide combination.

PMID- 18346607
TI  - The use of droperidol before and after the Food and Drug Administration black box
      warning: a survey of the members of the Society of Ambulatory Anesthesia.
AB  - STUDY OBJECTIVE: To determine the practice of members of the Society of
      Ambulatory Anesthesia (SAMBA) in the management of postoperative nausea and
      vomiting (PONV) before and after the Food and Drug Administration (FDA) black box
      warning on droperidol. DESIGN: Survey questionnaire. SETTING: The Society of
      Ambulatory Anesthesia. MEASUREMENTS: After institutional review board approval, a
      survey was posted on the SAMBA Web site from June 1, 2005, until October 30,
      2005. Visitors of the Web site were invited to participate in the survey. The
      survey was designed to elicit information about the management of PONV,
      particularly the use of droperidol, before and after the FDA black box warning.
      Participants were also asked about reasons for not using droperidol in their
      current practice and whether they believed that the black box warning was
      justified. MAIN RESULTS: Two hundred ninety-five physicians of 1,179 eligible
      SAMBA members completed the survey for a 25% response rate. For PONV prophylaxis,
      the choice of droperidol as a first-line agent decreased from 47% to 5% after the
      black box warning appeared (P < 0.0001). Similarly, for treatment of established
      PONV, the choice of droperidol decreased from 38% to 8% during this same period
      (P < 0.0001). A total of 261 (92%) of responders did not believe that the black
      box warning was justified. CONCLUSIONS: Although most surveyed practitioners
      believed that the FDA black box warning on droperidol is not justified, the use
      of this cost-effective agent has significantly declined.

PMID- 18346608
TI  - Comparison of the cardiovascular effects of isoflurane and sevoflurane as
      measured by magnetic resonance imaging in children with congenital heart disease.
AB  - STUDY OBJECTIVE: To compare the cardiovascular effects of isoflurane and
      sevoflurane at minimum alveolar concentration (MAC) = 1 in children with
      congenital heart disease using cardiac magnetic resonance imaging. DESIGN:
      Randomized, crossover, single-blinded study. SETTING: Tertiary-care teaching
      hospital. PATIENTS: 10 pediatric patients with congenital heart diseases
      scheduled to undergo cardiac magnetic resonance studies. INTERVENTIONS: Patients
      were randomized to receive either isoflurane or sevoflurane as the "first
      inhalation agent." After a period or more than 20 minutes, they were crossed over
      to receive the "second inhalation agent." MEASUREMENTS: Heart rate, mean arterial
      pressure (MAP), cardiac index, stroke volume index, and ejection fraction (EF) at
      one MAC for both agents were all recorded. MAIN RESULTS: Both isoflurane and
      sevoflurane caused a significant decrease in MAP from the baseline (P = 0.013).
      The mean values (+/-SD) of stroke volume (mL), cardiac index (L min(-1) m(-2)),
      and EF (%) for isoflurane versus sevoflurane were 21.5 (+/-9.2) versus 19.6 (+/
      6.2), 4.1 (+/-1.2) versus 3.7 (+/-0.87), and 64.2 (+/-14.5) versus 62.5 (+/
      13.8), respectively. CONCLUSION: Both isoflurane and sevoflurane were found to be
      comparable in terms of cardiovascular effects.

PMID- 18346609
TI  - Minimal threshold for stimulating catheters.
AB  - A patient undergoing total knee replacement was fitted with a stimulating femoral
      catheter for postoperative analgesia. After the catheter was secured to the skin,
      the minimal stimulatory threshold was verified again and found to be extremely
      low (0.00-0.01 mA; pulse width, 0.1 ms). However, in spite of this situation, no
      paresthesia or pain was experienced by the patient. Use of the catheter resulted
      in satisfactory analgesia with no complications noted during the hospital stay or
      at follow-up three months later. When the nerve stimulator was sent to our
      biomedical engineering department to verify the accuracy of its current output,
      it was found to be functioning adequately. Neurostimulation is a complex
      phenomenon that is far from being completely understood. On the basis of this
      single report, we cannot recommend the routine use of a threshold inferior to 0.2
      mA for neural electrolocation. However, we do not advocate the requirement of
      strict numerical thresholds either. Further research is needed to understand the
      relationship linking stimulatory threshold and distance between needle (or
      catheter) tip and nerve.

PMID- 18346610
TI  - Carbon dioxide absorber as a cause of high airway pressures.
AB  - We investigate an incident in which a carbon dioxide absorber caused difficulty
      with ventilation. The problem as it developed throughout the anesthetic, and
      clues that led to the determination that the carbon dioxide canister was the
      problem, is discussed.

PMID- 18346611
TI  - Massive retrograde acute type B aortic dissection in a postpartum woman with a
      family history of Marfan syndrome.
AB  - Acute aortic dissection is rare but potentially catastrophic complication of
      pregnancy. Aortic root enlargement, congenital bicuspid aortic valve disease, and
      Marfan syndrome have been identified as critical risk factors for peripartum
      aortic dissection. Most of the aortic dissections reported to date involve the
      ascending aorta and occur before delivery, but only a few cases of postpartum
      aortic dissection have been described. In this report, we discuss the management
      of a multigravid parturient with an extensive family history of Marfan syndrome
      who developed a massive retrograde type B aortic dissection 7 days after a normal
      spontaneous vaginal delivery.

PMID- 18346612
TI  - Bilateral thoracic paravertebral block for abdominoplasty.
AB  - Thoracic bilateral paravertebral block is a technique commonly used in the
      ambulatory setting for numerous plastic surgery procedures. Paravertebral block
      has not been reported with abdominoplasty surgery. This case series explores this
      anesthetic technique in the inpatient and day patient setting.

PMID- 18346613
TI  - Special doctor's docket: discovery of patient safety materials in the Veterans
      Affairs system.

PMID- 18346614
TI  - Lipmann and Anfinsen: Nobel biochemists of Beecher's anesthesia laboratory.
AB  - Henry K. Beecher performed blood pH and gas analysis on patients in the 1940s,
      though the biochemical technology was not widely available until the 1950s. Two
      of Beecher's biochemist coworkers, Fritz Lipmann and Christian B. Anfinsen, went
      on to earn Nobel Prizes.

PMID- 18346615
TI  - Coronary vasospasm during anesthesia induction: awareness, recognition, possible
      mechanisms, anesthetic factors, and treatment.
AB  - We describe a patient who developed severe ST-segment elevation, pulseless
      ventricular tachycardia, and cardiac arrest during induction of general
      anesthesia. This transient ST-segment elevation may have been the result of
      coronary artery spasm. Awareness of this variant of coronary artery vasospasm-
      Prinzmetal angina--in patients without clear symptoms or established ischemic
      heart disease, is the key to successful outcome. Recommended preparations and
      treatments are preoperative calcium channel blockers, nitroglycerin available
      intraoperatively, reduction of endogenous or exogenous catecholamines, and
      vigilant monitoring.

PMID- 18346616
TI  - Beware of the twisted guidewire.

PMID- 18346617
TI  - Penile prosthesis, spinal anesthesia, and priapism.

PMID- 18346618
TI  - A solution for occlusion of the pilot balloon tube on the endotracheal tube.

PMID- 18346619
TI  - Postoperative transient ischemic attack in a patient with radiation-induced
      internal carotid artery stenosis.

PMID- 18346621
TI  - Animal research in CAM: Is it still an issue?

PMID- 18346622
TI  - Reflexology in the management of low back pain: a pilot randomised controlled
      trial.
AB  - OBJECTIVE: The current study was designed as a pilot study for a randomised
      controlled trial to investigate the effectiveness of reflexology in the
      management of low back pain (LBP). MATERIALS AND METHODS: Participants suffering
      non-specific LBP were recruited and randomised into either a reflexology or a
      sham group. Patients and outcome assessor were blinded to group allocation. Each
      patient received either a 40 min reflexology treatment or sham treatment
      (according to group allocation) once per week for six consecutive weeks. The
      primary outcome measure was pain (visual analogue scale), secondary outcome
      measures were the McGill pain questionnaire, Roland-Morris disability
      questionnaire, and SF-36 health survey. Outcome measures were performed at
      baseline, week 6, week 12 and week 18. RESULTS: VAS scores for pain reduced in
      the treatment group by a median value of 2.5 cm, with minimal change in the sham
      group (0.2 cm). Secondary outcome measures produced an improvement in both groups
      (McGill pain questionnaire: 18 points in the reflexology group and 11.5 points in
      the sham group). Results indicate that reflexology may have a positive effect on
      LBP. CONCLUSION: Reflexology appears to offer promise as a treatment in the
      management of LBP; however, an adequately powered trial is required before any
      more definitive pronouncements are possible.

PMID- 18346623
TI  - Complementary therapies in the management of low back pain: a survey of
      reflexologists.
AB  - OBJECTIVE: To investigate current management of low back pain (LBP) by
      reflexologists. METHODS: A postal survey of reflexologists (n=500) sampled from
      the International Institute of Reflexology. The questionnaire used investigated a
      range of areas including: professional details, reflexology training and
      practice, views and experiences of reflexology, reflexology and LBP, and views on
      other complementary therapies. RESULTS: Response rate was 49.6% (n=248). The
      majority of respondents were female (95%), and were primarily employed within
      another profession such as nursing or teaching. Respondents perceived reflexology
      to have a positive effect on relieving LBP (94.3%) and to provide more benefit
      than simply relaxation. Practitioners also commented on other treatment effects,
      e.g. improving sleep patterns, decreasing anxiety and stress. It was reported
      that other healthcare practitioners, including general practitioners, referred
      patients to reflexologists for treatment. DISCUSSION: Respondents considered
      reflexology to be an effective therapy for LBP. Further work is warranted to
      investigate the potential role of such treatment in the management of this
      prevalent and intractable condition.

PMID- 18346624
TI  - Homoeopathic versus conventional treatment of children with eczema: a comparative
      cohort study.
AB  - OBJECTIVES: To assess, over a period of 12 months, whether homoeopathic treatment
      could influence eczema signs/symptoms and quality of life (QoL) compared with
      conventional treatment. DESIGN: Prospective multi-centre cohort study. SETTING:
      Children with eczema aged 1-16 years were recruited from primary care practices.
      INTERVENTIONS: Conventional versus homoeopathic treatment. OUTCOME MEASURES:
      Patients (or parents) assessed eczema symptoms by numerical rating scales as well
      as disease-specific Atopie Lebensqualitaets-Fragebogen (ALF) and general quality
      of life (KINDL, KITA) at 0, 6 and 12 months. RESULTS: A total of 118 children
      were included: 54 from homoeopathic (mean age+/-S.D. was 5.1+/-3.3 years; 56%
      boys) and 64 from conventional practices (6.2+/-3.8 years; 61% boys). Eczema
      symptoms (assessed by patients or their parents) improved from 0 to 12 months for
      both treatment options, but did not differ between the two groups: 3.5-2.5 versus
      3.4-2.1; p=0.447 (adjusted). Disease-related quality of life improved in both
      groups similarly. In the subgroup of children aged 8-16 years the general quality
      of life showed a better trend for conventional treatment compared with
      homoeopathic treatment (p=0.030). CONCLUSIONS: This observational study is the
      first long-term prospective investigation to compare homoeopathic and
      conventional treatment of eczema in children. Over a period of 12 months, both
      therapy groups improved similarly regarding perception of eczema symptoms
      (assessed by patients or parents) and disease-related quality of life.

PMID- 18346625
TI  - The role of a homoeopathic preparation compared with conventional therapy in the
      treatment of injuries: an observational cohort study.
AB  - OBJECTIVES: To assess the use, effectiveness and safety of a homoeopathic
      preparation (Traumeel) compared with conventional therapies in the treatment of
      trauma and injuries. METHODS: Multi-centre, prospective, comparative
      observational cohort study of patients with various musculoskeletal injuries.
      German physicians who were using homoeopathy in addition to conventional medicine
      included patients. Patients treated with Traumeel were compared with patients
      managed conventionally. The primary outcome measure was the rate of resolution of
      the principal symptoms (i.e. pain and inflammatory symptoms) at the end of
      therapy. RESULTS: Sixty-nine Traumeel treated and 64 conventionally treated
      patients fitted the selection criteria. The most common diagnoses were acute
      injuries (sprains, strains, contusions, etc.) of the ankles, knees and hands.
      There were no significant differences between demographic and anamnestic baseline
      characteristics of both groups. Complete resolution of the principal symptom at
      the end of therapy occurred in 41 (59.4%) patients in the homoeopathy group
      versus 37 (57.8%) patients in the conventional group. No adverse events were
      reported in the Traumeel group compared to six adverse events (6.3%) in the
      conventional group. Physician-assessed tolerability was significantly better in
      the Traumeel group (P=0.001). CONCLUSION: Traumeel is as effective as
      conventional medicines in the management of mild to moderate injuries in this
      population. Traumeel was safe in use and judged by physicians to be better
      tolerated than conventional medicines. This study contributes to the case for a
      broad clinical effectiveness of Traumeel in the treatment of acute injuries and
      trauma.

PMID- 18346626
TI  - Longitudinal changes in the disability level of the elders with low back pain
      after auriculotherapy.
AB  - OBJECTIVE: To evaluate the longitudinal changes in the disability level of elders
      with LBP after receiving auriculotherapy. DESIGN: Randomized controlled trial.
      SETTINGS: Sixty participants who were 60 years old or above and who were
      suffering from LBP were recruited from five hostels for the elders in Hong Kong.
      INTERVENTIONS: The participants were randomly allocated to receive a 3-week
      session of auriculotherapy using either semen vaccariae (control group=30) or
      magnetic pellets (experimental group=30). Seven auricular acupoints that are
      expected to have an effect on LBP were selected. MAIN OUTCOME MEASURES:
      Assessment data were collected at five points of time: (i) baseline, (ii) about
      1.5 weeks of treatment, (iii) 3 weeks of treatment, (iv) 2 weeks post-treatment,
      and (v) 4 weeks post-treatment using the modified Aberdeen low back pain
      disability scale (Chinese). RESULTS: When the rate of change was compared between
      the two groups at each point of time starting from the baseline, those in the
      experimental group demonstrated significant improvement in the overall disability
      level, pain/sensation, and physical and functional abilities at 1.5 weeks of
      treatment (p<0.001), 3 weeks of treatment (p<0.001), 2 weeks post-treatment
      (p<0.001), and 4 weeks post-treatment (p<0.001). CONCLUSION: Longitudinal changes
      in the improvement of disability level were found among the elders with low back
      pain after receiving auriculotherapy using magnetic pellets.

PMID- 18346627
TI  - The use of CAM in a New Zealand-based general practice: a multiple case-study.
AB  - OBJECTIVE: To explore the factors which underpin the healthcare consumers'
      decision-making to use CAM in the primary setting. DESIGN: An explorative,
      multiple case-study of seven convenience-sampled participants where in-depth,
      semi-structured interviews were employed. RESULTS: The findings showed that
      participants would continue to utilise CAM, even where CAM had no scientific
      evidence. The participants believed that CAM should be integrated into mainstream
      healthcare service delivery. CONCLUSIONS: There are few international studies
      that have reported on the utilisation and prevalence of CAM within the General
      Practice (GP) or clinic setting. The reasons why clients select specific CAM
      therapies, where they are offered in these settings, remain unclear. This study,
      however, casts further light on this matter.

PMID- 18346628
TI  - CAM practitioners in integrative practice in New South Wales, Australia: a
      descriptive study.
AB  - OBJECTIVES: The aim of this study was to examine the role of complementary and
      alternative medical (CAM) practitioners in integrative practices where general
      practitioners (GPs) and CAM practitioners were co-located. DESIGN: This study
      used grounded theory, a qualitative methodology from the interpretive paradigm.
      SETTING: A total of 23 integrative practitioners (10 general practitioners and 13
      naturopaths) were interviewed. The informants were drawn from 16 integrative
      practices and one non-integrative general medical practice. RESULTS: In 11 out of
      16 integrative practices the CAM practitioners yielded their primary contact role
      to the GPs. CAM practitioners were restricted to expanding the range of treatment
      options available to patients. However, the role of the CAM practitioners was
      influenced by the level of CAM training the GP(s) in the practice had undertaken.
      The more CAM training the GPs had undertaken, the more CAM practitioners were
      enlisted as diagnosticians as well as treatment providers. CONCLUSION: CAM
      practitioners in integrative practices had an accessory role to the GPs in the
      practice, deferring diagnosis and assessment activities to the GPs. However,
      where GPs had significant training in CAM, the CAM practitioner's role included
      both treatment and diagnostic activities.

PMID- 18346629
TI  - Capturing the value of complementary and alternative medicine: including patient
      preferences in economic evaluation.
AB  - Complementary and alternative medicine (CAM) is growing in popularity among
      patients, for an increasing range of conditions. However, current provision of
      CAM in the National Health Service in the UK is limited, patchy and disparate,
      which results in considerable inequity and patient unease. This has led to an
      escalation in the debate about the role of CAM within the NHS. Lack of evidence
      about the cost effectiveness of CAM therapies compared with other forms of care
      is often cited as the main reason for the reluctance of funders to integrate CAM
      into mainstream service provision. Cost-effectiveness relies on evidence about
      costs and benefits. Cost data are relatively straightforward to collect but it
      has proved difficult to value the complete package of benefits offered by CAM,
      likely to be both process and outcome based, in a way that can be compared with
      alternatives. Stated preference discrete choice modelling (SPDCM), a method of
      healthcare evaluation growing in popularity, uses information about patient
      preferences to identify the important characteristics of an intervention or
      method of delivering care and how patients value these. SPDCM is a method that
      could be used to evaluate the 'added value' provided by CAM and thus supply
      evidence on cost-effectiveness that policy makers could use in configuring
      service provision.

PMID- 18346630
TI  - How to put hypnosis into a placebo pill?
AB  - Many case studies and several controlled clinical trials have indicated the
      effectiveness of hypnotherapy for some medical conditions. However, because of
      methodological inadequacies hypnotherapy is still criticized for not having
      strong scientific evidence to support its claims. While randomized placebo
      controlled clinical trial is generally accepted as the gold standard study
      design, creating a credible placebo control for hypnotherapy is a major
      challenge. This paper recommends "neutral hypnosis" as a credible placebo control
      for hypnotherapy trials.

PMID- 18346631
TI  - Natural killer cells and lung transplantation, roles in rejection, infection, and
      tolerance.
AB  - Despite improvements in surgical technique, organ preservation,
      immunosuppression, and management of infection, the long term survival following
      lung transplantation remains low, mainly due to immune mediated complications
      such as acute and chronic rejection. Almost all immunosuppressive agents used in
      the prophylaxis and treatment of rejection following lung transplantation are
      targets of T cell maturation, function or proliferation, which in theory should
      cause sufficient disruption of the adaptive immune system to prevent graft
      rejection. However the five year survival rate of only 50% suggests this is not
      the case. More recent evidence suggests that NK cells may play a significant role
      in immune processes following lung transplantation. This article reviews the
      literature on the potential function of NK cells in rejection, infection,
      malignancy and tolerance following lung transplantation.

PMID- 18346632
TI  - Activation of Tim-3-Galectin-9 pathway improves survival of fully allogeneic skin
      grafts.
AB  - T cell immunoglobulin and mucin domain (Tim)-3 is a molecule expressed on
      terminally differentiated murine Th1 cells but not on Th2 cells. Identification
      of Galectin-9 as a ligand for Tim-3 has now firmly established the Tim-3-Galectin
      9 pathway as an important regulator of Th1 immunity, which results in apoptosis
      of Th1 cells. Here, we demonstrate that engagement of Tim-3 by mouse recombinant
      Galectin-9 remarkably suppresses allograft rejection and improves survival of
      allogeneic skin grafts. Furthermore, administration of recombinant Galectin-9
      decreases Tim-3 positive cells in draining lymph node and selectively inhibits
      production of IFN-gamma after skin transplantation. At last, even low dose of
      Galectin-9 (1 microg/ml) can obviously inhibit TCR crosslinking-induced primary T
      cell proliferation in vitro. These observations suggest that Tim-3-Galectin-9
      pathway plays an important role in the termination of productive Th1-immune
      response and could lead to developing novel therapies in transplant medicine.

PMID- 18346633
TI  - Heart allograft acceptance induced by anti-CD3 antibody in high-responder rats:
      effect on foxp3 and cytokine expression and graft infiltration.
AB  - The ability of anti-T cell monoclonal antibody G4.18 and polyclonal anti
      lymphocyte serum (ALS) to induce long-term graft survival was examined in a high
      responder rat heart transplant model. Heterotopic heart allografts were performed
      from PVG rat strain donors to high-responder Lewis recipients. Immunosuppressive
      properties of G4.18 and ALS were investigated by immunohistochemistry and PCR
      analysis. Untreated graft rejection was 8.5 days while treatment with 1 ml ALS
      prolonged survival to 11.5 days (p=0.01). Treatment with 7 mg/kg G4.18 on days 1
      and 3 prolonged survival to >100 days (p=0.002 vs. control and p=0.002 vs. ALS)
      but did not induce tolerance. Acceptance was associated with marked inhibition of
      cellular infiltration and inflammatory cytokine expression and only a brief,
      slight increase in Foxp3:T cell ratio in the graft and no increase in the spleen.
      In conclusion, G4.18 treatment led to long-term heart transplant survival
      associated with marked inhibition of early inflammation. Failure to develop
      tolerance was associated with a lack of early accumulation of Foxp3 cells in the
      graft or spleen.

PMID- 18346634
TI  - Efficacy of tacrolimus in inhibiting inflammation caused by carrageenan in a
      murine model of air pouch.
AB  - BACKGROUND: Tacrolimus (Tac) is a macrolide immunosuppressant drug isolated from
      Streptomyces tsukubaensis, widely used in organ transplantation. OBJECTIVE: This
      study examined the effect of tacrolimus administered by oral route (p.o.) on
      inflammation in mouse subcutaneous air pouch triggered by carrageenan (Cg 1%).
      METHODS: The air pouch was induced as described by Beninca et al. [Beninca JP,
      Montanher AB, Zucolotto SM, Schenkel EP, FrodeTS. Anti-inflammatory effects of
      the Passiflora edulis: forma flavicarpa Degener inhibition of leukocytes, enzymes
      and pro-inflammatory cytokine levels in the air pouch model, in mice. Food Chem
      2007; 104(3); 1097-1105.]. The inflammatory parameters (leukocytes, exudation,
      myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, as well as
      nitrate/nitrate concentrations (NO(x)), interleukin-1 beta (IL-1beta), chemokine
      to neutrophil (KC) and tumor necrosis factor-alpha (TNF-alpha) levels were
      analysed 24 h after injection of carrageenan. RESULTS: Tacrolimus, indomethacin
      and dexamethasone significantly inhibited leukocytes, neutrophils and exudation
      (P<0.05) when they were administered 0.5 h before inflammation. These drugs,
      under the same conditions, decreased MPO and ADA activities (P<0.05), NO(x) and
      IL-1beta levels (P<0.01). Tacrolimus and indomethacin, but not dexamethasone,
      inhibited KC levels (P<0.01). On the other hand, tacrolimus and dexamethasone,
      but not indomethacin, decreased TNF-alpha levels (P<0.01). CONCLUSIONS: Results
      of this study indicate that tacrolimus has an important anti-inflammatory
      property, showing not only inhibition of pro-inflammatory mediators release, but
      also inhibition of activated leukocyte infiltration into the site of
      inflammation. Furthermore, these results showed that most of the anti
      inflammatory actions of tacrolimus were similar to those observed in animals
      treated with either indomethacin or dexamethasone.

PMID- 18346635
TI  - Analysis of the serine protease function of porcine factor I produced by liver
      cells for xenotransplantation.
AB  - The use of a bioartificial liver with pig liver cells in the treatment of
      fulminant hepatic failure has already begun as a clinical trial in several
      countries. Therefore, studies on plasma complement regulatory proteins of the pig
      are necessary, because the liver produces them. Complement factor I is a serine
      protease that cleaves C3b and C4b. The DNA sequences of factor I have been
      reported in many species, with the noted exception of pigs. In this study,
      porcine factor I was cloned and an open reading frame of 1794 base pairs were
      identified. The predicted amino acid sequence maintained a relatively high
      homology compared to those of other mammals, especially in the serine protease
      (SP) region. The cell membrane-bound forms of the porcine and the human SP domain
      of factor I were constructed. Amelioration of complement-mediated cell lysis by
      these molecules was then tested, using several kinds of sera and Chinese hamster
      ovary (CHO) cell transfectants. Both molecules had a suppressing effect on pig,
      human and dog complements, indicating little species-specificity. Further studies
      of other plasma complement regulatory proteins produced from pig liver cells will
      need to be considered as the primary feature of the pig bioartificial liver.

PMID- 18346636
TI  - The effects of antibody treatment on regulatory CD4(+)CD25(+) T cells.
AB  - Current therapeutic antibodies, at least some, possess the capacity to induce
      immune tolerance in experimental models with allo-grafts or autoimmune diseases.
      Clinical application of humanized or chimeric antibodies to treat graft rejection
      or autoimmune diseases is presently underway. It is now becoming clear that
      immune tolerance can be acquired in some cases due to the action of regulatory T
      cells (Tregs), especially CD4(+)CD25(+) Tregs. In addition to their inhibition on
      immune response, some antibodies could promote tolerance induction in organ
      transplantation and autoimmune diseases essentially through the induction of
      Tregs. In this manuscript, we review the recent progress on the effects of
      therapeutic antibodies on the development, phenotypic changes and functions of
      CD4(+)CD25(+) Tregs.

PMID- 18346637
TI  - Alloantigen-specific prolongation of allograft survival in recipient mice treated
      by alloantigen immunization following ultraviolet-B irradiation.
AB  - It is well documented that ultraviolet (UV) radiation present in sunlight
      suppresses immune responses. However, the majority of studies documenting the
      immunosuppressive effects of UV irradiation have been carried out in animals
      exposed to UV irradiation before immunization. Here, we report that recipient
      mice exposed to UV irradiation 7 days after immunization with a donor alloantigen
      exhibited prolongation of allograft survival in an alloantigen-specific manner.
      Recipient mice (H-2(b)) intravenously immunized with 2 x 10(7) allogeneic spleen
      cells (H-2(b/d)) 7 days before UV irradiation (40 kJ/m(2)) showed prolonged
      survival of allografts presenting the alloantigen used for sensitization (H
      2(b/d)), but not third-party allografts (H-2(b/k)). Adoptive transfer experiments
      revealed that CD4(+) T cells in UV-irradiated recipients were responsible for
      this prolongation. CD4(+) T cells that could transfer the suppression produced
      large amounts of interleukin (IL)-10, but not IL-4. The effect of UV irradiation
      on alloantigen-specific immunosuppression was cancelled by administration of an
      anti-IL-10 monoclonal antibody. These results indicate that UV irradiation given
      after alloantigen immunization induces alloantigen-specific type 1 regulatory T
      cell-like regulatory T cells that prolong allograft survival and imply that the
      difficulties associated with predicting donor-related organ availability in
      transplantation can be dealt with, given the effectiveness of UV irradiation
      after immunization.

PMID- 18346638
TI  - The phenotypical and functional characteristics of cord blood monocytes and CD14(
      /low)/CD16(+) dendritic cells can be relevant to the development of cellular
      immune responses after transplantation.
AB  - Umbilical cord blood (UCB) has been used as an alternative source of
      haematopoietic progenitors for transplantation presenting advantages over bone
      marrow (BM) that are related with known shortages of newborns' immune system at
      adaptive and innate levels. Using flow cytometry, we studied the expression of
      Toll-like receptors (TLRs) and chemokine receptors (CKRs) and the production of
      pro-inflammatory cytokines by monocytes and CD14(-/low)/CD16(+)DCs from
      peripheral blood (PB; n=10), and umbilical cord blood (UCB; n=10). CKRs and
      cytokines were studied before and after stimulation of cells with LPS plus IFN
      gamma. We also identified the two populations in normal bone marrow samples (BM;
      n=5). BM presented lower frequencies of both studied populations when compared to
      UCB and PB. CD14(-/low)/CD16(+)DCs presented a pattern of TLR expression
      different from mature monocytes reflecting distinct functions for these two
      populations. UCB cells presented reduced expression of TLR-4 and lower capability
      to produce cytokines prior stimulation. The populations studied presented
      different patterns of CKR expression reflecting distinct migratory pathways.
      Moreover, UCB cells presented higher expressions of CXCR4 and CCR7 that may be
      involved in immune system maturation and stem cell homing. Monocytes and CD14(
      /low)/CD16(+)DCs present functional and phenotypical characteristics that may
      contribute to the lower incidence and severity of GVHD.

PMID- 18346639
TI  - TNFalpha in patients with end-stage heart failure on medical therapy or supported
      by a left ventricular assist device.
AB  - BACKGROUND: In the heart elevated levels of TNFalpha can cause lethal heart
      failure, like Dilated Cardiomyopathy (DCM). The level of TNFalpha production is
      in part determined by promoter gene polymorphisms. We investigated whether the
      TNFalpha promoter gene polymorphism is in this way involved in the outcome of end
      stage heart failure and predicts whether patients require left ventricular assist
      device (LVAD) support or can be kept on medical therapy (MT)while awaiting heart
      transplantation (HTx). As most patients in this study received a heart
      transplant, the role of the TNFalpha polymorphisms in transplant rejection was
      studied as well. METHODS AND RESULTS: In twenty nine patients with DCM, 35
      patients with Ischemic Heart Disease (IHD; both on MT), 26 patients on LVAD
      support and 61 cardiac transplant donors TNFalpha plasma level was detected by
      EASIA. In both patients groups high levels of TNFalpha plasma levels was observed
      however, in patients supported by LVAD this increase was much higher compared to
      patients on MT. Furthermore, this increase seems to be associated with the TNF 1
      allele ('G' at position -308) instead of the TNF2 allele (A at position -308).
      The promoter polymorphisms at positions -238, -244 and -308 were observed by
      polymerase chain reaction and sequencing. Polymorphism at positions -238, -244
      and -308 did not show any relevant differences between the groups. However, at
      position -308, a trend of a higher incidence of the TNF2 allele (an "A" at
      position -308) in DCM patients compared to donors was shown. The distribution of
      the TNF1 and TNF2 alleles was not different in patients on medical therapy
      compared to the patients supported by a LVAD. No association was found between
      patients' TNFalpha promoter gene polymorphism and rejection. However, patients
      that received a donor heart with the TNF2 allele developed more rejection
      episodes, compared to patients that received a donor heart with the TNF1 allele.
      CONCLUSION: TNFalpha levels are high in patients with end-stage heart failure on
      MT, but even higher in patients on LVAD support. These high TNFalpha plasma
      levels however, are not correlated with the TNF2 allele but seems to be
      associated with the TNF1 allele. Furthermore, in HTx the donor TNFalpha gene seem
      to play a more important role in severity of acute rejection than that of the
      patient.

PMID- 18346640
TI  - Short-term anti-CD25 monoclonal antibody treatment and neogenetic
      CD4(+)CD25(high) regulatory T cells in kidney transplantation.
AB  - CD4(+)CD25(high) T cells named regulatory T (Treg) cells are generated and play a
      key role in the induction and maintenance of transplant tolerance in organ
      recipients. Interleukin-2 (IL-2) enhance the development of effector cells and is
      essential for generation of Treg cells. The effect of the anti-CD25 monoclonal
      antibody (anti-CD25mAb) induction therapy on the neogenetic CD4(+)CD25(high)Treg
      cells is important for therapeutic strategies in kidney transplant. To clarify
      the question, a prospective study was conducted in 21 living donor kidney
      transplant recipients who randomly divided into the anti-CD25mAb group
      (Daclizumab) with 11 patients and the control group with 10 patients. The
      frequency of CD4(+)CD25(high)Treg cells in total CD4(+) T cells was analyzed by
      flow cytometry and FoxP3 expression by RT-PCR in peripheral blood, and results
      were compared at day 0, 3, 13, 17, 27 posttransplantation. There was no
      significant difference in patient characteristics and allograft survival. The
      present study showed that in vivo antigen-specific Treg cells population were
      generated and expanded after transplant. Both groups showed a significant
      increase in the frequency of CD4(+)CD25(high)Treg cells and higher level of FoxP3
      mRNA after transplantation while the serum creatinine declined. Compared with the
      control group, recipients with anti-CD25mAb injection had significantly lower
      percentage of CD4(+)CD25(high) in total CD4(+) cells (1.13%+/-0.13% vs 1.94%+/
      0.22%, P=0.00; 3.75%+/-0.28% vs 7.11%+/-0.51%, P=0.00) on day 3, 17 after
      transplantation. While, the percentage was not significantly different on day 10,
      27 (3.72%+/-0.19% vs 4.36%+/-0.28%, P=0.08; 7.84%+/-0.35% vs 8.56%+/-0.36%,
      P=0.16). However, there was not obvious difference in Foxp3 expression level
      associated with the source of the CD4(+)CD25(high)Treg cells at the different
      time point after transplant. Our data indicated that CD4(+)CD25(high)Treg cells
      were transiently affected by anti-CD25mAb, without depletion. In conclusion, the
      short-term treatment with anti-CD25mAb might not prevent the production,
      proliferation of neogenetic Treg cells in organ transplant.

PMID- 18346641
TI  - A pilot study of GC/MS-based serum metabolic profiling of acute rejection in
      renal transplantation.
AB  - AIMS: Acute allograft rejection is one of the important complications after renal
      transplantation, and it is a deleterious factor for long-term graft survival.
      Rejection is a complex pathophysiologic process, which has been explained by
      transcriptome and proteome in RNA transcripts and proteins level respectively.
      How are serum metabolite levels in response to acute rejection? Can metabolite
      levels in serum be used to diagnose and explain acute renal allograft rejection?
      METHODS: Gas chromatograph-mass spectrometry (GC-MS) was used to analyze serum
      metabolome in 22 recipients of acute rejection and 15 stable renal transplant
      recipients. RESULTS: 46 endogenous metabolites included amino acid, fatty acid,
      carbohydrate and other intermediate metabolites were identified in 37 recipients.
      Principal component analysis based on these metabolites discriminated acute
      rejection group from stable recipients. Among these metabolites, the levels of 17
      metabolites were significant higher in rejection group than those in stable
      group. These included amino acid (phenylalanine, serine, glycine, threonine,
      valine), carbohydrate (galactose oxime, glycose, fructose), carboxylic acid,
      lipids and other metabolite such as lactate, urea and myo-inositol. The levels of
      5 metabolites of alanine, lysine, leucine, aminomalonic acid and tetradecanoic
      acid were low in rejection group compared to stable group. The prediction
      accuracy of acute rejection was 77.3% and stable function was 100% by supervised
      clustering based on these 22 metabolites. CONCLUSIONS: This study demonstrated
      that metabolic profile was changed in response to rejection process and renal
      function can be reflected by serum metabolite levels. This study showed potential
      capability to diagnose acute rejection by metabolome analysis.

PMID- 18346642
TI  - Microarray analysis of MicroRNA expression in acute rejection after renal
      transplantation.
AB  - MicroRNAs (miRNAs) are noncoding RNA molecules of 21 to 24 nt that regulate the
      expression of target genes in a post-transcriptional manner. Evidence indicates
      that miRNAs play essential roles in embryogenesis, cell differentiation and
      pathogenesis of human diseases. Kidney transplantation to treat end-stage renal
      disease has evolved rapidly from the first successful transplantations to the
      current widespread use of grafts from both cadaveric and living donors. But acute
      rejection is still a strong risk factor for chronic rejection in recipients of
      renal grafts. To investigate possible mechanisms, we describe a comparison
      between miRNA expression profile of acute rejection and the controls. Through
      microarray analysis and quantitative real-time RT-PCR confirmation, we identified
      20 miRNAs differently expressed in acute rejection after renal transplantation.
      Our data thus indicate that miRNAs were potentially involved in the pathogenesis
      of acute rejection, and miRNAs can help to diagnosis, treat and prevent acute
      rejection after renal transplantation.

PMID- 18346643
TI  - Remembrance of things past: a summary of the development of cerebrovascular
      terminology in modern times.

PMID- 18346644
TI  - Cerebral venous thrombosis: analysis of a multicenter cohort from the United
      States.
AB  - OBJECTIVE: The data regarding diagnosis, prognosis, management, and outcome of
      patients with cerebral venous thrombosis are limited from the United States.
      METHODS: Patients with diagnosis of cerebral venous thrombosis were identified by
      International Classification of Diseases, Ninth Revision coding system at 10
      centers in the United States during a 10-year period by retrospective chart
      review (1991-1997) or prospective enrollment (1997-2001). In all, 232 patients
      were screened for study inclusion and 182 of these patients were included in the
      study. RESULTS: The age range was 13 to 82 years (mean 38 years). Hypercoagulable
      state was the most common predisposing factor followed by pregnancy, malignancy,
      and homocystinemia. Neurologic examination revealed normal findings in 69
      patients (38%); 37 (20%) were comatose, 59 (32%) had papilledema, and 71 (39%)
      had hemiparesis. In all, 61 patients (33%) had evidence of hemorrhage by computed
      tomography/magnetic resonance imaging. A total of 27 patients (15%) were treated
      with thrombolysis and 124 (68%) with anticoagulation. Overall mortality was 13%
      (n = 24). One-year follow up was available for 96 patients (53%). Of these, 26
      (27%) were healthy, 43 (45%) were ambulatory with assistance, and 27 (28%) were
      still bedridden. On multivariate analysis, the best predictors of a poor outcome
      were coma at presentation (odds ratio 15.2 [95% confidence interval; 1.5-66]) and
      intracerebral hemorrhage (odds ratio 8.7 [95% confidence interval; 1.3-34.5]).
      CONCLUSION: Clinical and radiologic presentation of cerebral venous thrombosis in
      the United States is not much different from other parts of world but spectrum
      and frequency of predisposing factors are different. Number of patients treated
      with thrombolysis is higher as compared with other reported series of such
      patients. Coma at presentation and intracerebral hemorrhage were the strongest
      predictors of poor outcome, which is comparable with other series.

PMID- 18346645
TI  - Vertebrobasilar revascularization rates and outcomes in the MERCI and multi-MERCI
      trials.
AB  - OBJECTIVE: Mortality of 40% to 86% and good outcomes in only 13% to 21% of
      patients beg for treatment options for basilar occlusion. This study determined
      outcomes of patients with vertebrobasilar occlusion treated with mechanical
      embolus removal in cerebral ischemia (MERCI) retriever mechanical thrombectomy.
      METHODS: Patients with vertebrobasilar occlusion in the MERCI and Multi-MERCI
      trials received treatment up to 8 hours after symptom onset. Recanalization was
      determined after retriever use and adjunctive therapy. Mortality and good
      outcomes, modified Rankin scale score 0-3, were determined at 90 days in patients
      who were recanalized and not recanalized. RESULTS: Recanalization occurred in 21
      of 27 (78%) patients. Mortality was 44% and good outcomes were seen in 41%.
      Patients with recanalization tended to have better outcomes than those without.
      CONCLUSIONS: Outcomes in patients with vertebrobasilar occlusions treated with
      the MERCI retriever compared favorably with natural history reports and tended to
      be better in those patients with recanalization.

PMID- 18346646
TI  - Study of the propensity for hemorrhage in Hispanic Americans with stroke.
AB  - OBJECTIVE: Multiple sources document a higher proportion of intraparenchymal
      hemorrhage (HEM) in Hispanic (HIS) than white (WHI) patients with stroke. We
      sought an explanation for this phenomenon through analysis of multiple variables
      in our hospital-based stroke population. METHODS: We performed univariate and
      multivariate analysis of risk factors in our HIS and WHI patients with stroke to
      identify differences that might account for a greater propensity for HEM in HIS
      patients. RESULTS: Multivariate analysis disclosed that the risk of HEM
      correlated significantly with untreated hypertension (HTN), HIS ethnicity, and
      heavy alcohol intake. A negative correlation was found for hyperlipidemia and
      diabetes. Our HIS patients with stroke had a greater prevalence of untreated HTN
      and heavy alcohol intake, with HIS men being at greatest risk. CONCLUSIONS: HIS
      patients with stroke in our hospital-based population appear relatively more
      prone to HEM than do WHI patients. This risk correlates with a greater likelihood
      of having untreated HTN and heavy alcohol intake, more so for HIS men. The
      explanation appears to be a relative lack of health awareness and involvement in
      our health care system. The possibility that HIS ethnicity itself constitutes a
      biological risk factor for HEM remains a matter of speculation. Validation of
      this work with community data should lead to remediation through a community
      based effort.

PMID- 18346647
TI  - Intravenous recombinant tissue plasminogen activator improves arterial
      recanalization rates and reduces infarct volumes in patients with hyperdense
      artery sign on baseline computed tomography.
AB  - BACKGROUND: We sought to evaluate arterial recanalization as measured by changes
      in the presence of hyperdense artery sign (HAS) on initial and 24-hour computed
      tomography scans in patients treated with recombinant tissue plasminogen
      activator (rt-PA) or placebo, and to assess the effect of rt-PA on patient
      outcomes in this population. METHODS: Patients in the National Institute of
      Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial composed the study
      group. We determined the percentage of patients with HAS in rt-PA- and placebo
      treated groups who had persistence (HAS +/+) or resolution (HAS +/-) of HAS on 24
      hour computed tomography, and compared outcomes in those with resolution or
      persistence of the sign in these treatment groups. RESULTS: Baseline HAS occurred
      in 79 of 604 eligible patients (13%). The two treatment groups were similar,
      although patients treated with rt-PA were significantly older. Of the 79 patients
      with HAS on baseline computed tomography scan, 14 of 37 (38%) treated with rt-PA
      had resolution of HAS at 24 hours compared with 7 of 42 (17%) treated with
      placebo (P = .03). Infarct volumes at 24 hours were significantly smaller in
      patients treated with rt-PA with resolution of the sign, compared with those who
      had persistence of the sign (P = .004). In our analysis, functional outcomes were
      not significantly improved based on resolution of HAS in either treatment group.
      There were 4 symptomatic ICHs in the rt-PA-treated group with HAS as compared
      with two in the placebo-treated group. CONCLUSION: Among patients with HAS at
      baseline in the NINDS rt-PA Stroke Trial, intravenous rt-PA increased
      recanalization as measured by resolution of HAS and reduced infarct volumes at 24
      hours.

PMID- 18346648
TI  - Stroke in Qatar: a first prospective hospital-based study of acute stroke.
AB  - BACKGROUND: Stroke is a major cause of morbidity and mortality in Qatar.
      OBJECTIVES: The aim of our study was to determine types of strokes, the
      associated risk factors, clinical presentation, outcome, and time to hospital
      admission among Qatari and non-Qatari patients as well as young and nonyoung
      patients. METHODS: We conducted a hospital-based prospective observational study
      including all patients admitted to Hamad Medical Corporation with first-ever
      stroke from September 15, 2004, to September 14, 2005. A stroke was defined
      according to World Health Organization criteria. RESULTS: Stroke was confirmed in
      270 patients of whom 217 (80.4%) had ischemic stroke and 53 (19.6%) had
      hemorrhagic stroke. Male patients predominated in all types of stroke. The main
      risk factors for stroke were hypertension and diabetes, whereas lacunar infarct
      was the most common subtype of ischemic stroke. Risk factor profiles were similar
      between Qatari and non-Qatari patients except for hypercholesterolemia, which was
      observed with a higher frequency in Qatari compared with non-Qatari patients with
      ischemic stroke. There were significant differences between the young and
      nonyoung patients with ischemic stroke with respect to risk factors, ejection
      fraction, ventricular wall-motion abnormalities, time to hospital admission, and
      outcome. Most patients arrived at the hospital more than 3 hours from stroke
      onset because of unawareness of stroke symptoms. The overall in-hospital
      mortality was 9.3%. CONCLUSIONS: Hypertension and diabetes mellitus were the main
      risk factors for stroke in Qatar, whereas lacunar infarct was the most common
      subtype. Significant differences between the young and nonyoung patients were
      observed with respect to risk factors, ejection fraction, ventricular wall-motion
      abnormalities, time to hospital admission, and outcome.

PMID- 18346649
TI  - Is beta-thalassemia trait a protective factor against ischemic cerebrovascular
      accidents?
AB  - OBJECTIVE: In this research, we sought to determine the association between beta
      thalassemia trait and ischemic cerebrovascular accident (CVA). METHODS: In acase
      control study, 148 patients with thromboembolic cerebrovascular events were
      evaluated for the presence of hypertension, diabetes mellitus, hyperlipidemia,
      and beta-thalassemia trait. A total of 156 age- and sex-matched patients with no
      cardiac or cerebrovascular diseases, serving as the control group, were also
      investigated for the above-mentioned risk factors. RESULTS: We found that 6.1% of
      patients with ischemic CVA and 12.2% of the control group had beta-thalassemia
      trait (P = .066). In male patients, the negative association between ischemic CVA
      and presence of beta-thalassemia trait was significant (P = .008). In patients,
      the prevalence of hypertension was also significantly different between those
      with and without beta-thalassemia trait (P = .01); those with beta-thalassemia
      trait had a lower mean blood pressure than those without the trait. CONCLUSION:
      beta-Thalassemia trait may have a protective effect against ischemic CVA that
      might be caused by the lower arterial blood pressure observed in those with this
      trait.

PMID- 18346650
TI  - Baseline characteristics of patients with acute ischemic stroke in a suburban
      area of Thailand.
AB  - BACKGROUND: Development in stroke care during the past two decades has greatly
      reduced mortality and dependence in many developed countries. However, we still
      lack information about baseline characteristics of patients with ischemic stroke
      in Thailand, especially in suburban areas. OBJECTIVE: We sought to study
      characteristics of Thai patients with ischemic stroke, including carotid stenosis
      and aspirin nonresponders. METHODS: In this preliminary study, we included all
      patients with acute/subacute ischemic stroke/transient ischemic attack from
      August 2006 to July 2007. Information about baseline characteristics, including
      medication, was collected. Carotid duplex studies were performed in all patients
      who were clinically stable. RESULTS: In all, 194 patients with ischemic
      stroke/transient ischemic attack were studied. Of patients, 62% came to the
      hospital within 24 hours after onset of symptoms, and 8% arrived within 3 hours.
      Stroke in the young was 13%. Of patients, 28% had already been on aspirin
      (aspirin nonresponder) before having a new ischemic stroke. Significant carotid
      stenosis was found in 17% (31 of 184) of the patients. CONCLUSION: Although fewer
      patients came to the hospital within 3 hours after stroke onset, other baseline
      characteristics of Thai patients with ischemic stroke do not much differ from
      those of other Asian countries.

PMID- 18346651
TI  - Vascular risks and complications in diabetes mellitus: the role of helicobacter
      pylori infection.
AB  - Patients with diabetes mellitus (DM) are at risk for Helicobacter pylori
      infection. This infection has been linked to atherosclerosis and its vascular
      complications. The aim of this study was to evaluate the: (1) prevalence of H
      pylori infection in patients with DM; (2) association between diabetic vascular
      complications and H pylori infection; and (3) influence of H pylori infection on
      atherosclerosis and inflammatory biomarkers. In this study, we evaluated 80
      patients with DM for atherosclerosis; cardiac, cerebral, and peripheral vascular
      diseases; retinopathy; neuropathy; and nephropathy. We estimated the blood levels
      of glucose, glycosylated hemoglobin, complete blood cell count, erythrocytic
      sedimentation rate, lipid profile, tumor necrosis factor-alpha, interleukin (IL)
      6, and anti-H pylori IgG antibodies. H pylori infection was detected in 85% of
      patients versus 76.7% for control subjects. Carotid artery intima-media thickness
      was significant in H pylori-infected patients. IL-6 and tumor necrosis factor
      alpha were significantly associated with H pylori infection. In multivariate
      analysis, blood glucose, triglycerides, erythrocytic sedimentation rate, IL-6,
      and tumor necrosis factor-alpha increased the odds for atherothrombotic cause of
      cerebral ischemia in H pylori infection. We concluded that H pylori infection is
      common in DM and seems to be linked to the presence of atherosclerosis and
      ischemic cerebrovascular stroke. This effect could be mediated by increasing
      cytokine levels.

PMID- 18346652
TI  - Local thrombolysis in patients with dural venous thrombosis unresponsive to
      heparin.
AB  - OBJECTIVE: We sought to study the efficacy and complications of local
      thrombolysis using urokinase in cases of cortical vein thrombosis unresponsive to
      conventional heparin therapy. METHODS: Patients with clinical and radiologic
      diagnosis of cortical vein thrombosis were taken for local thrombolysis using
      femoral vein approach if they did not respond to heparin therapy after 5 days of
      administration of the drug. Urokinase was used as the thrombolytic agent and dose
      was decided depending on the recanalization obtained during the procedure.
      RESULTS: Of the 3 patients treated, two had complete recanalization and one had
      partial recanalization. Two had dramatic recovery of the clinical symptoms. One
      patient in whom thrombolysis was delayed had partial recovery. None had any
      complications related to the treatment. CONCLUSION: Local thrombolytic therapy is
      effective in recanalization of thrombosed sinus. It is worth considering in dire
      circumstances especially when a patient fails to respond to heparin. However,
      randomized controlled trials are necessary before any firm recommendations can be
      made as to whether it can be used as a primary modality of treatment in cases of
      cortical vein thrombosis.

PMID- 18346653
TI  - The paradoxical flow hypothesis of the carotid artery: supporting evidence from
      phase-contrast magnetic resonance imaging.
AB  - OBJECTIVE: Narrowing of the poststenotic internal carotid artery (ICA) has been
      found to be associated with reduced risk of ipsilateral stroke. A paradoxical
      mechanism has been hypothesized to explain this finding: narrowing of the distal
      normal (reference) ICA is associated with low blood flow rates (Q) in the
      stenotic ICA, and lower Q causes lower risk of ipsilateral stroke, perhaps by an
      associated reduction in mechanical stress on the atherosclerotic plaque. The
      purpose of this study was to confirm that the reference ICA diameter (RICAD) is
      indeed predictive of Q, a finding that would indirectly support the hypothesis of
      a relationship between lower Q and lower risk of ipsilateral stroke. METHODS:
      Magnetic resonance imaging from 38 patients was included in the study. The study
      included 17 stenotic carotid arteries and 59 normal carotid arteries. All
      patients underwent contrast-enhanced magnetic resonance angiography from which
      measurements were obtained of the RICAD and the internal-common carotid diameter
      ratio. Patients underwent cardiac-gated, velocity-encoded phase-contrast magnetic
      resonance imaging for measurement of Q. RESULTS: Mean flow rates differed between
      stenotic (4.3 +/- 1.7 mL/s) and normal (5.4 +/- 1.7 mL/s) arteries (P = .02).
      RICAD was found to be a predictor of Q for stenotic arteries (P = .009) and for
      all arteries (P = .025) but not for the group of normal arteries (P = .162).
      Right-left differences in RICAD were highly predictive of right-left differences
      in Q in the subgroup of individuals with normal arteries (P < .001) and in the
      group of all participants (P < .001). Internal-common carotid diameter ratio was
      not found to be a statistically significant predictor of Q in the subgroup of
      stenotic arteries (P = .156). CONCLUSIONS: This study demonstrated that, as
      hypothesized, RICAD is correlated with Q.

PMID- 18346654
TI  - Adolescent brain development: forging new links?

PMID- 18346655
TI  - Converging evidence leaves policy behind: sex education in the United States.

PMID- 18346656
TI  - Physical activity in adolescents: from associations to interventions.

PMID- 18346657
TI  - A midcourse review of the healthy people 2010: 21 critical health objectives for
      adolescents and young adults.
AB  - As part of Healthy People 2010, a national consensus panel identified 21 Healthy
      People 2010 objectives as critical to adolescent and young adult health. These
      objectives span six areas: mortality, unintentional injury, violence, mental
      health and substance use, reproductive health, and the prevention of chronic
      disease during adulthood. Progress on these objectives was reviewed as part of
      the Healthy People 2010 Midcourse Review. The review found little or no
      improvement on most objectives. Expert recommendations call for broad, population
      based efforts to improve adolescent health. However, changes in health policy are
      largely issue-based and occur incrementally.

PMID- 18346658
TI  - The teen brain: insights from neuroimaging.
AB  - Few parents of a teenager are surprised to hear that the brain of a 16-year-old
      is different from the brain of an 8-year-old. Yet to pin down these differences
      in a rigorous scientific way has been elusive. Magnetic resonance imaging, with
      the capacity to provide exquisitely accurate quantifications of brain anatomy and
      physiology without the use of ionizing radiation, has launched a new era of
      adolescent neuroscience. Longitudinal studies of subjects from ages 3-30 years
      demonstrate a general pattern of childhood peaks of gray matter followed by
      adolescent declines, functional and structural increases in connectivity and
      integrative processing, and a changing balance between limbic/subcortical and
      frontal lobe functions, extending well into young adulthood. Although
      overinterpretation and premature application of neuroimaging findings for
      diagnostic purposes remains a risk, converging data from multiple imaging
      modalities is beginning to elucidate the implications of these brain changes on
      cognition, emotion, and behavior.

PMID- 18346659
TI  - Abstinence-only and comprehensive sex education and the initiation of sexual
      activity and teen pregnancy.
AB  - PURPOSE: The role that sex education plays in the initiation of sexual activity
      and risk of teen pregnancy and sexually transmitted disease (STD) is
      controversial in the United States. Despite several systematic reviews, few
      epidemiologic evaluations of the effectiveness of these programs on a population
      level have been conducted. METHODS: Among never-married heterosexual adolescents,
      aged 15-19 years, who participated in Cycle 6 (2002) of the National Survey of
      Family Growth and reported on formal sex education received before their first
      sexual intercourse (n = 1719), we compared the sexual health risks of adolescents
      who received abstinence-only and comprehensive sex education to those of
      adolescents who received no formal sex education. Weighted multivariate logistic
      regression generated population-based estimates. RESULTS: Adolescents who
      received comprehensive sex education were significantly less likely to report
      teen pregnancy (OR(adj) = .4, 95% CI = .22- .69, p = .001) than those who
      received no formal sex education, whereas there was no significant effect of
      abstinence-only education (OR(adj) = .7, 95% CI = .38-1.45, p = .38). Abstinence
      only education did not reduce the likelihood of engaging in vaginal intercourse
      (OR(adj) = .8, 95% CI = .51-1.31, p = .40), but comprehensive sex education was
      marginally associated with a lower likelihood of reporting having engaged in
      vaginal intercourse (OR(adj) = .7, 95% CI = .49-1.02, p = .06). Neither
      abstinence-only nor comprehensive sex education significantly reduced the
      likelihood of reported STD diagnoses (OR(adj) = 1.7, 95% CI = .57-34.76, p = .36
      and OR(adj) = 1.8, 95% CI = .67-5.00, p = .24 respectively). CONCLUSIONS:
      Teaching about contraception was not associated with increased risk of adolescent
      sexual activity or STD. Adolescents who received comprehensive sex education had
      a lower risk of pregnancy than adolescents who received abstinence-only or no sex
      education.

PMID- 18346660
TI  - Support for comprehensive sexuality education: perspectives from parents of
      school-age youth.
AB  - PURPOSE: Controversy about school-based sexuality education in public schools has
      continued over the past decade, despite mounting evidence that comprehensive
      sexuality education effectively promotes sexual health and that parents support
      these programs in public schools. The present study replicates and expands upon
      previous findings regarding public views on school-based sexuality education.
      METHODS: One thousand six hundred five parents of school-age children in
      Minnesota responded to telephone surveys in 2006-2007 (63% participation rate),
      including items regarding general sexuality education, 12 specific topics, the
      grade level at which each should be taught, and attitudes toward sexuality
      education. RESULTS: The large majority of parents supported teaching about both
      abstinence and contraception (comprehensive sexuality education [CSE]; 89.3%),
      and support was high across all demographic categories of parents. All specific
      sexuality education topics received majority support (63.4%-98.6%), even those
      often viewed as controversial. Parents believed most topics should first be
      taught during the middle school years. Parents held slightly more favorable views
      on the effectiveness of CSE compared to abstinence-only education, and these
      views were strongly associated with support for CSE (odds ratio [OR](CSE) = 14.3;
      OR(abstinence) = 0.11). CONCLUSIONS: This study highlights a mismatch between
      parents' expressed opinions and preferences, and actual sexuality education
      content as currently taught in the majority of public schools. In light of broad
      parental support for education that emphasizes multiple strategies for prevention
      of pregnancy and sexually transmitted infections (including abstinence), parents
      should be encouraged to express their opinions on sexuality education to
      teachers, administrators, and school boards regarding the importance of including
      a variety of topics and beginning instruction during middle school years or
      earlier.

PMID- 18346661
TI  - Correlates of physical activity guideline compliance for adolescents in 100 U.S.
      Cities.
AB  - PURPOSE: This study assessed the rates and correlates of adolescents' compliance
      with national guidelines for physical activity. METHODS: A cross-sectional phone
      survey of adolescents and their parents was conducted in the 100 largest cities
      in the United States in 2005. Adolescents ages 14-17 years (n = 6125) were asked
      how many days during the previous week and during a typical week they were
      physically active for at least 60 minutes. Compliance was defined as 5+ days per
      week. Parents provided data on teen's age and race/ethnicity, parental education
      level, annual household income, and region of residence. Associations among these
      variables and compliance with physical activity guidelines were examined.
      RESULTS: Approximately 40% of the females and 57% of the males complied with the
      national physical activity guidelines. Logistic regression indicated that for
      both genders, compliance was significantly associated with having higher
      household income and that, for females only, compliance declined significantly
      with age. Region of residence did not predict compliance for either gender.
      CONCLUSION: A majority of the girls and a large portion of the boys failed to
      meet the current guidelines, thereby increasing their risks of multiple health
      problems. Targeting intervention resources for low income teens and older
      adolescent teen girls is recommended.

PMID- 18346662
TI  - Patterns and determinants of physical activity in U.S. adolescents.
AB  - PURPOSE: The objectives of this study were to describe longitudinal trends in
      adolescent physical activity in a sample of U.S. adolescents and to assess the
      effect of multiple individual, parental, and environmental factors on initial
      level and rates of change in adolescent physical activity. METHODS: Study
      subjects were 12,812 boys and girls 10 to 18 years of age who were participating
      in the Growing Up Today Study and their mothers. We used accelerated longitudinal
      analysis to describe trajectories of physical activity from 1997-1999, and random
      effects linear mixed models to determine which factors were independently
      associated with baseline physical activity and changes in physical activity over
      time. RESULTS: Mean hours of physical activity ranged from 7.3-11.6 hours per
      week in boys and from 8.0-11.2 hours per week in girls. Physical activity was
      best modeled as a quadratic function of age, increasing until early adolescence
      and declining after age 13 in boys and girls. Multivariable modeling demonstrated
      that variables associated with physical activity level at baseline in boys and
      girls were age, body mass index, psychosocial variables, personal attitudes about
      body shape, perceived peer attitudes about body shape/fitness, parental attitudes
      about physical activity, parental physical activity, and environmental barriers
      to physical activity. Age was the only factor that predicted change in physical
      activity over time. CONCLUSIONS: Interventions to increase physical activity in
      adolescents should begin before adolescence. Interventions may be more effective
      if they are multimodal and focus on modifiable individual, parental, and
      environmental factors.

PMID- 18346663
TI  - The roles of personality traits and negative life events on the episodes of
      depressive symptoms in nonreferred adolescents: a 1-year follow-up study.
AB  - PURPOSE: To evaluate the influences of personality traits and nonsevere life
      events on depressive episodes in a 1-year follow-up in nonreferred adolescents.
      METHODS: Participants were 2,773 students aged 12 to 16 years randomly selected
      from six middle schools in Taiwan who were assessed both at baseline for
      personality traits and depressive symptoms and at 1 year later for negative life
      events and depressive symptoms. Two, single, or no episodes of depression were
      based on whether the scores of the Center for Epidemiologic Studies Depression
      crossed over the cutoff of 28 at two time points. Multinomial logistic regression
      analyses were used to correlate personality or negative life events, which were
      trichotomized by means of tertiles or number of events, with the episodes of
      depressive symptoms. RESULTS: After controlling for possible confounders, only
      elevated neuroticism was associated with a single episode of depressive symptoms,
      whereas a medium level or above of neuroticism, extraversion, or negative life
      events all exhibited association with the occurrence of two episodes. No
      interactions were found between all personality traits or between personality and
      negative life events. CONCLUSIONS: The relations of personality traits or
      nonsevere life events to depressive symptoms depend on whether the episode is an
      initial one. A high level in neuroticism is a critical vulnerability factor for
      the initiation of depressive symptoms in adolescents. Once the threshold has been
      surpassed, the influences of various personality traits and nonsevere life events
      on the subsequent depressive symptoms become cumulative and exhibit a dose
      response relationship.

PMID- 18346664
TI  - Self-esteem in children and adolescents after septic shock caused by Neisseria
      meningitidis: scars do matter.
AB  - PURPOSE: To investigate self-esteem and its relation to scars, amputations, and
      orthopedic sequelae in children and adolescents long term after meningococcal
      septic shock (MSS) caused by Neisseria meningitidis. METHODS: The Dutch versions
      of the Self-Perception Profile for Children (SPP-C; 8-11 years) and the Self
      Perception Profile for Adolescents (SPP-A; 12-17 years) were used to assess self
      esteem. The Patient and Scar Assessment Scale (PSAS) was used to evaluate scar
      severity. RESULTS: MSS boys aged 8-11 years achieved higher, more favorable
      scores on self-esteem, whereas same-aged MSS girls reported comparable levels of
      self-esteem compared with the respectively same-aged reference boys and girls.
      MSS boys and girls aged 12-17 years obtained unfavorable scores on self-esteem
      compared with respectively same-aged reference boys and girls. Overall gender did
      not have an effect on self-esteem. Severity of illness, age at time of illness,
      and age at time of follow-up were not significant predictors of self-esteem. MSS
      adolescents with scars reported lower global self-worth than MSS adolescents
      without scars. The worse MSS children evaluated their scars, the worse their
      outcomes on social acceptance. The worse MSS adolescents evaluated their scars,
      the worse their outcomes on close friendship, but the better their outcomes on
      social acceptance and behavioral conduct. CONCLUSION: In this cross-sectional
      study, favorable outcomes for self-esteem were found in MSS children, whereas MSS
      adolescents reported lower self-esteem compared with reference adolescents.
      Adolescents with scars reported lower global self-worth than MSS adolescents
      without scars.

PMID- 18346665
TI  - Effectiveness of an intensive, school-based intervention for teen mothers.
AB  - PURPOSE: This study evaluated the effectiveness of a secondary teen pregnancy
      prevention intervention that includes school-based social work services
      coordinated with comprehensive health care for teen mothers and their children.
      METHODS: A prospective cohort study compared subsequent births to teen mothers
      followed for at least 24 months or until age 20 years (whichever was longer)
      compared with matched subjects from state data. Analyses were based on intent to
      treat and included chi(2), survival, and cost-benefit analysis. RESULTS: Subjects
      included 63 girls (97% eligible, 99% African-American, mean age 16 years). A
      propensity-matched comparison group (n = 252) did not differ from subjects.
      Participation in program components was good: (1) group meetings: 76%; (2) case
      management: 95%; (3) coordinated medical care: 63%. The majority of subjects used
      contraception (93%), with greater use of medroxyprogesterone associated with
      participation in coordinated medical care (80% vs. 50%, p = .0145). Subsequent
      births were more common in the comparison group (33%) than among subjects (17%)
      (p = .001), and survival curves were significantly different (p = .007) (hazard
      ratio = 2.5). There was a trend toward fewer births with increased participation
      in medical care (p = .08) and case management (p = .08) but not with group
      meetings. Cost savings were calculated as $19,097 per birth avoided or $5,055 per
      month. CONCLUSIONS: The intervention was effective in reducing subsequent births
      to teens; however selection bias of school enrollment cannot be excluded by this
      study. The cost savings of delayed births outweigh the expenses of this intensive
      model.

PMID- 18346666
TI  - Predictors of sexual risk behaviors among newly homeless youth: a longitudinal
      study.
AB  - PURPOSE: To longitudinally examine the association between newly homeless youth
      individual factors (sociodemographic characteristics, depression, substance use),
      and structural factors, such as living situation (family, institution,
      nonfamily), with sexual risk behaviors. METHODS: A cohort of newly homeless youth
      from Los Angeles County (N = 261; aged 12-20 years) was interviewed at baseline,
      3, 6, 12, 18, and 24 months. At each assessment youth were asked about symptoms
      of depression (using the Brief Symptom Inventory), substance use, living
      situation, and sexual risk behaviors (number of sexual partners and condom use).
      Random effects models were used to determine the effects of predictors on the
      number of sexual partners and on condom use over time, by gender. RESULTS: At
      baseline, 77% of youth had been sexually active, increasing to 85% of youth at 24
      months of follow-up. For predictors of multiple sexual partners, among male
      youth, these included living in nonfamily settings and using drugs; among
      females, living situation was not predictive of having multiple sexual partners
      but drug use was. For condom use, among females, living in a nonfamily setting
      and drug use decreased the odds of always using condoms; for males, no factors
      were found to be predictive of condom use. CONCLUSIONS: Living with nonfamily
      members and drug use appear to be the most salient in explaining sexual risk
      among newly homeless youth. Our findings indicate that interventions aimed at
      reducing sexual risk behaviors, and thereby reducing sexually transmitted
      diseases and HIV among newly homeless youth, need to help youth in finding
      housing associated with supervision and social support (family and institutional
      settings) as well as aim to reduce drug use.

PMID- 18346667
TI  - Effects of stigma on the mental health of adolescents orphaned by AIDS.
AB  - PURPOSE: By 2010, an estimated 18.4 million children in Sub-Saharan Africa will
      be orphaned by AIDS. Research in South Africa shows that AIDS orphanhood is
      independently associated with heightened levels of psychological problems. This
      study is the first to explore the mediating effects of stigma and other factors
      operating on a community level, on associations between AIDS orphanhood and
      mental health. We assessed the associations of four risk factors that can
      potentially be addressed at a community level (bullying, stigma, community
      violence, and lack of positive activities) with psychological problems and
      orphanhood status. METHOD: One thousand twenty-five participants aged 10-19 were
      recruited from deprived urban settlements in South Africa. The sample included
      adolescents orphaned by AIDS (n = 425), adolescents orphaned by non-AIDS causes
      (n = 241), and nonorphaned adolescents (n = 278). Participants were interviewed
      using standardized psychological measures of depression, anxiety, posttraumatic
      stress, peer problems, delinquency, and conduct problems. Information on risk
      factors and demographic characteristics were also assessed. RESULTS: AIDS
      orphaned adolescents reported higher levels of stigma and fewer positive
      activities than other groups. There were no reported differences on bullying or
      community violence. All community-level risk factors were associated with poorer
      psychological outcomes. Multivariate analyses controlling for age and gender
      showed that experience of stigma significantly mediated associations between AIDS
      orphanhood and poor psychological outcomes. CONCLUSIONS: Reduction of AIDS
      related stigma could potentially reduce adverse psychological outcomes among AIDS
      orphaned adolescents.

PMID- 18346668
TI  - Adolescent travel patterns: pilot data indicating distance from home varies by
      time of day and day of week.
AB  - We conducted a pilot study using new technology to track adolescent "place."
      Using Global Positioning System (GPS)-enabled cell phones, we recruited and
      tracked 15 female adolescents for a 1-week period. Distance away from home was
      greatest in the evenings on weekends or holidays. The greatest percentage of time
      spent more than 1 kilometer away from home was also during these times. Such GPS
      technology holds promise for future adolescent health research in allowing more
      specific and dynamic measurement of where adolescents spend time.

PMID- 18346669
TI  - Young adolescent responses to different question formats assessing
      race/ethnicity.

PMID- 18346670
TI  - Lawyer for children left out, left alone, and left behind: the personal odyssey
      of an adolescent health advocate.

PMID- 18346671
TI  - Challenges in the comorbid condition.

PMID- 18346672
TI  - Insomnia and comorbid psychiatric disorders.
AB  - Defining the relationship between sleep disturbances and psychiatric disorders is
      a thought-provoking task and is becoming even more challenging because it is
      apparent that insomnia is not simply a typical symptom of a psychiatric disorder
      but may actually be a predictor (or independent risk factor) for the development
      of such a condition. Studies have shown that depressed patients not only have
      disturbances in sleep continuity but have reduced slow wave sleep and
      disinhibited REM sleep. In particular, REM sleep regulation is characterized by
      shortened REM latency and increased REM density. It has been suggested that the
      reciprocal interaction between REM and nonREM sleep, driven by inhibitory
      aminergic and excitatory cholinergic activity, becomes unbalanced in depression.
      Exposure to cholinergic stimulants reduces REM latency, particularly in major
      depressive disorder. In fact, it has been shown that healthy individuals at high
      risk for developing depression have greater sensitivity to cholinergic
      stimulation than those not at high risk. While the causality of the insomnia
      depression relationship is debated, epidemiological studies have indicated that
      insomnia is an independent risk factor for depression and other psychiatric
      disorders. As we learn more about the interplay between these pathophysiologies,
      we will be able to make better treatment decisions for our patients.

PMID- 18346673
TI  - Insomnia and sleep-disordered breathing.
AB  - Approximately half of patients with sleep-disordered breathing (SDB) also
      experience insomnia. The relationship between these two common sleep disorders is
      complex and unclear but patients with both SDB and insomnia have poorer sleep
      quality and are more likely to have psychiatric disorders than those with SDB
      alone. SDB is more common in men than women; however, the incidence of comorbid
      insomnia is greater in women with SDB than in men. The management of comorbid SDB
      and insomnia involves the screening of patients with insomnia or psychiatric
      disorders for SDB; although interviews may be effective in diagnosing SDB in
      patients with insomnia, polysomnography can diagnose veiled SDB. To address
      comorbid SDB and insomnia therapies should be aimed at both disorders. Patients
      should first be encouraged to improve their sleep hygiene and make lifestyle
      changes to improve sleep. Treatments for SDB include continuous positive airway
      pressure and oral appliances, while upper airway surgery may improve sleep
      outcomes in some patients. The use of pharmacological drugs such as hypnotics for
      the treatment of insomnia in patients with SDB remains controversial.

PMID- 18346674
TI  - Insomnia in patients with neurodegenerative conditions.
AB  - Comorbid insomnia and other sleep disturbances are common in patients with
      neurodegenerative disorders, such as Parkinson's or Alzheimer's disease. Insomnia
      in patients with neurological conditions may occur as a direct consequence of the
      disease itself or may be secondary to factors associated with the condition, such
      as pain, depression or the effects of medications. Disturbed sleep can have a
      significant impact on the patient's cognitive and physical function and may be
      associated with distress and depression. Insomnia also impacts patients' and
      caregivers' quality of life and is often cited as one of the primary reasons for
      patient institutionalization. Management of insomnia in patients with
      neurological disorders should be individualized to each patient's needs. The type
      of insomnia and any underlying causes of disturbed sleep must first be
      determined. Non-pharmacological interventions, such as behavioral modification,
      should be considered for all patients. Bright light therapy may be an effective
      treatment option for patients with disturbed sleep-wake patterns. Medications
      causing sleep problems should be withdrawn or doses and/or timing adjusted,
      whenever possible. Several pharmacological options are available to relieve the
      symptoms of insomnia as short-term treatment.

PMID- 18346675
TI  - Understanding insomnia through cognitive modelling.
AB  - Cognitive models of insomnia have received growing support in recent years and
      are embraced by the current diagnostic framework. Many people with insomnia
      report that mental events, such as intrusive thoughts or a racing mind, prevent
      them from achieving or maintaining sleep. Dysfunctional cognition may play an
      important role in perpetuating insomnia, with many individuals with
      psychophysiological insomnia reporting a distorted perception of sleep.
      Neurocognitive studies have indicated that high-frequency EEG activity associated
      with cognitive processes is enhanced in patients with insomnia at or around sleep
      onset, which may distort the individual's judgement about sleep initiation and
      duration. A subtype of psychophysiological insomnia has been proposed--attention
      intention-effort (AIE) syndrome--that takes into consideration the interaction
      between behavioral and cognitive factors in the development and maintenance of
      insomnia. A series of studies from the University of Glasgow Sleep Centre using
      cognitive probe tasks has provided insight into this pathway, particularly with
      regard to the role of attention bias towards sleep stimuli in mediating insomnia.
      Further research is required to explore the cortical correlates of attention
      bias, investigate AIE as a potential causal mechanism of insomnia and examine AIE
      in other insomnia groups.

PMID- 18346676
TI  - Conclusion: challenges in the comorbid condition.

PMID- 18346677
TI  - Human physiological models of insomnia.
AB  - Despite the wide prevalence and important consequences of insomnia, remarkably
      little is known about its pathophysiology. Available models exist primarily in
      the psychological domain and derive from the demonstrated efficacy of behavioral
      treatment approaches to insomnia management. However, these models offer little
      specific prediction about the anatomic or physiological foundation of chronic
      primary insomnia. On the other hand, a growing body of data on the physiology of
      sleep supports a reasonably circumscribed overview of possible pathophysiological
      mechanisms, as well as the development of physiological models of insomnia to
      guide future research. As a pragmatic step, these models focus on primary
      insomnia, as opposed to comorbid insomnias, because the latter is by its nature a
      much more heterogeneous presentation, reflecting the effects of the distinct
      comorbid condition. Current understanding of the regulation of sleep and
      wakefulness in mammalian brain supports four broad candidate areas: 1) disruption
      of the sleep homeostat; 2) disruption of the circadian clock; 3) disruption of
      intrinsic systems responsible for the expression of sleep states; or 4)
      disruption (hyperactivity) of extrinsic systems capable of over-riding normal
      sleep-wake regulation. This review examines each of the four candidate
      pathophysiological mechanisms and the available data in support of each. While
      studies that directly test the viability of each model are not yet available,
      descriptive data on primary insomnia favor the involvement of dysfunctional
      extrinsic stress-response systems in the pathology of primary chronic insomnia.

PMID- 18346678
TI  - Acute gastrointestinal bleeding.

PMID- 18346679
TI  - Epidemiology of acute upper gastrointestinal bleeding.
AB  - Acute upper gastrointestinal bleeding is an important emergency situation.
      Population-based epidemiology data are important to get insight in the actual
      healthcare problem. There are only few recent epidemiological surveys regarding
      acute upper gastrointestinal bleeding. Several surveys focusing on peptic ulcer
      disease showed a significant decrease in admission and mortality of peptic ulcer
      disease. Several more recent epidemiological surveys show a decrease in incidence
      of all cause upper gastrointestinal bleeding. The incidence of peptic ulcer
      bleeding remained stable. Peptic ulcer bleeding is the most common cause of upper
      gastrointestinal bleeding, responsible for about 50% of all cases, followed by
      oesophagitis and erosive disease. Variceal bleeding is the cause of bleeding in
      cirrhotic patients in 50-60%. Rebleeding in upper gastrointestinal bleeding
      occurs in 7-16%, despite endoscopic therapy. Rebleeding is especially high in
      variceal bleeding and peptic ulcer bleeding. Mortality ranges between 3 and 14%
      and did not change in the past 10 years. Mortality is increasing with increasing
      age and is significantly higher in patients who are already admitted in hospital
      for co-morbidity. Risk factors for peptic ulcer bleeding are NSAIDs use and H.
      pylori infection. In patients at risk for gastrointestinal bleeding and using
      NSAIDs, a protective drug was only used in 10%. COX-2 selective inhibitors do
      cause less gastroduodenal ulcers compared to non-selective NSAIDs, however, more
      cardiovascular adverse events are reported. H. pylori infection is found in about
      50% of peptic ulcer bleeding patients. H. pylori should be tested for in all
      ulcer patients and eradication should be given.

PMID- 18346680
TI  - Epidemiology of lower gastrointestinal bleeding.
AB  - Lower GI bleeding is a very broad topic, which can encompass situations from a
      small amount of red blood on tissue paper associated with formed brown stool, to
      life-threatening severe haemorrhage. Much of the literature on this topic focuses
      on acute bleeding necessitating hospitalisation and urgent intervention. The
      literature that is available focuses primarily on medical intervention and
      support, which will be covered in another review in this series. Causes for lower
      GI bleeding include diverticular disease, vascular ectasia, ischemic,
      inflammatory or infectious colitis, colonic neoplasia (including post polypectomy
      bleeding), anorectal causes (including haemorrhoids, fissures and rectal
      varices), and small bowel lesions (Crohn's, vascular ectasia, Meckel's
      diverticula, and small bowel tumours). Different clinical series identified these
      lesions in varying frequencies. Factors associated with the development of acute
      lower GI bleeding include advanced age and use of non-steroidal anti-inflammatory
      medication. Colonoscopy is the single most frequent intervention in evaluating
      all the patients with lower GI bleeding. Determining the precise impact of
      colonoscopy on the outcome of lower GI bleeding is difficult due to the
      retrospective nature of many studies, and the frequent inability to definitively
      establish the exact bleeding site.

PMID- 18346681
TI  - Usefulness of prognostic indices in upper gastrointestinal bleeding.
AB  - Upper gastrointestinal haemorrhage remains a significant cause of hospital
      admission, with mortality rates up to 14%. In order to standardise and improve
      care, various scoring systems (e.g. Rockall, Blatchford and Baylor) have been
      developed to identify those individuals at high risk of requiring treatment
      (transfusion, endoscopic or surgical intervention) or of re-bleeding or death.
      There is also increasing interest in the utilisation of scoring systems to
      identify individuals at low risk of complications, as these may be discharged
      early, possibly with outpatient endoscopy. Most scoring systems are developed to
      predict outcomes in non-variceal bleeding. However, several indices are used to
      predict the outcome of advanced liver disease, including Child-Pugh and the Model
      of End-Stage Liver Disease (MELD). This chapter reviews all these aspects of the
      various scoring systems.

PMID- 18346682
TI  - Current endoscopic and pharmacological therapy of peptic ulcer bleeding.
AB  - Peptic ulcer bleeding is the most significant complication of ulcer disease,
      remaining the most important reason for upper gastrointestinal bleeding even in
      the era of Helicobacter eradication. Endoscopic triage and management plays a
      vital role in the handling of these patients, albeit in close collaboration with
      radiological and surgical expertise. Injection therapy, preferably with large
      volume epinephrine remains a core technology. Histoacryl and fibrin glue are more
      costly and less widely adopted alternatives. Mechanical measures are attractive
      and clips offer an excellent solution, particularly in soft tissues, and in
      combination with initial injection. Thermal methods with coagulation and coaptive
      axial force have similar performance characteristics. Increasingly, the
      combination of injection therapy with either a mechanical or thermal method
      appears the best option to achieve permanent haemostasis. PPIs for potent acid
      inhibition improves the clotting regardless of other treatment modalities. In the
      setting of rebleeding, patient and ulcer factors determine whether repeat
      endoscopy should be attempted, but the surgeon should be close at hand in this
      situation.

PMID- 18346683
TI  - Current endoscopic therapy of variceal bleeding.
AB  - Variceal ligation has proved more effective and safer than sclerotherapy and is
      currently the endoscopic treatment of choice for oesophageal varices. In acute
      bleeding, vasoactive drugs should be started before endoscopy and maintained for
      2-5 days. The efficacy of drugs is improved when associated with emergency
      endoscopic therapy. Antibiotic prophylaxis should also be used. To prevent
      rebleeding, both endoscopic ligation and the combination of beta-blockers and
      nitrates may be used. Adding beta-blockers improves the efficacy of ligation.
      Haemodynamic responders to beta-blockers+/-nitrates (those with a decrease in
      portal pressure gradient HVPG to <12 mmHg or by >20% of baseline) have a marked
      reduction in the risk of haemorrhage and will not need further treatment. Beta
      blockers significantly reduce the risk of a first haemorrhage in patients with
      large varices, and they improve survival. As compared to beta-blockers,
      endoscopic ligation reduces the risk of first bleeding without affecting
      mortality, and should be used in patients with contraindications or intolerance
      to beta-blockers.

PMID- 18346684
TI  - Acute variceal bleeding: pharmacological treatment and primary/secondary
      prophylaxis.
AB  - Variceal bleeding is one of the most severe complications of portal hypertension
      related to liver cirrhosis. Primary prophylaxis is considered mandatory in
      patients with cirrhosis and high-risk oesophageal varices, and once varices have
      bled, every effort should be made to arrest the haemorrhage and prevent further
      bleeding episodes. In acute variceal bleeding, vasoactive drugs that lower portal
      pressure should be started even before endoscopy, and should be maintained for up
      to 5 days. The choice of vasoactive drug should be made according to local
      resources. Terlipressin, somatostatin and octreotide can be used; vasopressin
      plus transdermal nitroglycerin may be used if no other drug is available. In
      variceal bleeding, antibiotic therapy is also mandatory. In primary and secondary
      prophylaxis, beta-blockers are the mainstay of therapy. In secondary prophylaxis
      (but not in primary prophylaxis) these drugs can be combined with organic
      nitrates.

PMID- 18346685
TI  - Management of lower gastrointestinal tract bleeding.
AB  - Acute bleeding from the colon and rectum is less frequent and less dramatic than
      haemorrhage from the upper gastrointestinal tract. In most cases, bleeding from
      the colon and rectum is self-limiting and requires no specific therapy.
      Diverticula and angiectasias are the most frequent sources of bleeding.
      Malignancy, colitis (inflammatory bowel disease, non-steroidal anti-inflammatory
      drugs, and infectious colitis), ischaemia, anorectal disorders, postpolypectomy
      bleeding, and HIV-related problems are less frequent causes. The recurrence rate,
      especially in diverticular bleeding, is high. Resuscitation and haemodynamic
      stabilisation of the patient is the first step in the management of colonic
      bleeding. Urgent colonoscopy is the method of choice for diagnosis and therapy.
      By analogy with peptic ulcer bleeding, risk stratification using stigmata of
      haemorrhage is gaining more importance. Modern endoscopic techniques such as
      injection therapy, thermocoagulation and mechanical devices seem to be effective
      in achieving haemostasis and avoiding precarious surgery. Angiography and nuclear
      scintigraphy are reserved for those patients in whom colonoscopy is not possible
      or has repeatedly failed to localise the bleeding site.

PMID- 18346686
TI  - Vascular lesions of the gastrointestinal tract.
AB  - Classification of vascular abnormalities of the gastrointestinal tract on the
      basis of anatomy and pathophysiology has recently been suggested. Angiodysplasia,
      an example of an arteriovenous lesion, may cause either acute or chronic
      bleeding. Diagnosis may be difficult. High-quality standard endoscopy, capsule
      endoscopy, and double-balloon enteroscopy are most efficacious. Therapy using
      argon plasma coagulation is currently preferred. Pharmacological therapy has been
      employed, but a final conclusion about its efficacy cannot yet be drawn.
      Dieulafoy lesion, an arterial type of vascular abnormality, is rare but serious.
      It can be responsible for severe haemorrhage. Mechanical endoscopic methods are
      the most efficacious. Gastric antral vascular ectasia (GAVE), a capillary lesion,
      can be safely biopsied; it coincides with several diseases (including liver
      cirrhosis), may cause chronic iron-deficiency anaemia, and is best treated by
      argon plasma coagulation. Haemangiomas, benign neoplastic lesions, usually occur
      as part of other specific syndromes; they are difficult to manage due to the
      multiplicity and size of the lesions.

PMID- 18346687
TI  - Obscure gastrointestinal bleeding: role of videocapsule and double-balloon
      enteroscopy.
AB  - Capsule endoscopy (CE), which allows the non-invasive visualisation of mucosa
      throughout the entire small bowel, has revolutionised the exploration of small
      bowel diseases, and particularly the evaluation of obscure gastrointestinal
      bleeding (OGIB) after a negative initial evaluation, including gastroscopy and
      colonoscopy. CE has a high negative predictive value and a higher diagnostic
      yield than all other modalities, such as radiology (small-bowel X-rays or
      computed tomography scan) or push enteroscopy. CE may be the preferred initial
      diagnostic choice in OGIB because of its non-invasive quality and better
      tolerance. Double-balloon enteroscopy, also known as push-and-pull enteroscopy,
      has recently been developed. It has made it possible not only to explore the
      small bowel but also to carry out therapeutic interventions deep in the small
      bowel without the need for surgical laparotomy. This exploration should be
      considered as a second-line exploration for OGIB in patients with a positive
      finding on CE requiring endoscopic follow-up for histology or intervention, and
      in patients in whom suspicion of a small-bowel lesion is high despite a negative
      CE.

PMID- 18346688
TI  - Therapeutic options for endoscopic haemostatic failures: the place of the surgeon
      and radiologist in gastrointestinal tract bleeding.
AB  - The management of gastrointestinal tract bleeding has changed dramatically due to
      improvements of interventional endoscopy and radiology. The place of the
      radiologist has become very important, not only for diagnostic modalities but
      also for therapeutic embolisation to control the bleeding. The place of the
      surgeon is limited to the situation where both these less invasive techniques
      have failed to stop the bleeding. For arterial bleeding in the whole GI tract,
      angiography with subsequent embolisation is performed after failed endoscopy. For
      variceal bleeding the preferred treatment after endoscopic failure is
      transjugular intrahepatic portosystemic stent shunting (TIPS). Surgery is only
      needed in exceptional cases. Embolisation can be performed successfully without
      compromising the bowel vascularisation or inducing ischaemia, whereas surgery has
      a high rate of complications and mortality. For treatment of GI bleeding a
      multidisciplinary team including a gastroenterologist, radiologist and surgeon is
      mandatory.

PMID- 18346689
TI  - The role of blood transfusion in the management of upper and lower intestinal
      tract bleeding.
AB  - Patients with gastrointestinal (GI) haemorrhage use 13.8% of all red blood cell
      transfusions in England. This review addresses the evidence for red blood cell,
      fresh frozen plasma and platelet transfusions in acute and chronic blood loss,
      from both the upper and lower intestinal tract. It reviews the indications for
      transfusion in GI bleeding, the haematological consequences of massive blood loss
      and massive transfusion, and the importance of managing coagulopathy in bleeding
      patients. It also looks at the safety and risks of blood transfusion, and
      provides clinicians with evidence to reduce unnecessary transfusion. Large
      controlled clinical trials of blood transfusion specifically in GI bleeding are
      required, along with further research into the use of adjuvant therapies such as
      recombinant activated factor VIIa. Changing clinician behaviour to reduce
      inappropriate blood transfusion remains a key target for future transfusion
      research.

PMID- 18346690
TI  - Future expectations in the prophylaxis of intestinal bleeding.
AB  - Prophylaxis of gastrointestinal bleeding is attempted in widely varying
      situations. In NSAID-induced peptic ulcer, the advantage of selective
      cyclooxygenase 2 inhibitors with regard to gastrointestinal damage has yet to be
      translated into an advantage in overall morbidity. Strategies for primary and
      secondary prevention of variceal bleeding have been established. Therapy tailored
      to hepatic venous pressure gradient has the potential to achieve clinical
      relevance. Several methods have been developed to prevent postpolypectomy
      bleeding, but their optimal risk-tailored application has yet to be demonstrated.
      Although octreotide treatment seems to be beneficial in reducing the blood loss
      from angiodysplasias, controlled studies to determine its optimal use are
      awaited. Stress-ulcer prophylaxis is commonly applied in critically ill patients.
      Although data indicate that H2-receptor antagonists and omeprazole are effective
      in preventing clinically significant bleeding, evidence for an advantage with
      respect to length of hospital or intensive-care-unit stay, as well as mortality,
      is still lacking. Since there is misuse of acid-suppressing drugs on regular
      wards, in-house guidelines may offer the potential for saving costs and reducing
      inappropriate prescription.

PMID- 18346691
TI  - Clinician assessment of guidelines that support common dental procedures.
AB  - Many common clinical dental procedures do not have high-quality clinical
      guidelines available. Clinical guidelines are considered an important tool for
      applying the evidence-based concept to dental practice. The main objective of
      this study was to assess if current clinical guidelines that are easily available
      to dental practitioners in electronic databases support common dental procedures.
      In addition, a useful model for the assessment of the quality of the guidelines
      is presented. The results of a literature search demonstrated a lack in both the
      number and quality of clinical dental guidelines that support common dental
      procedures. Nine selected guidelines were assessed using the Appraisal of
      Guidelines, Research, and Evaluation instrument (AGREE). Following the AGREE
      recommendation, only one guideline could be considered for use in dental
      practice. Four guidelines were also considered for use in practice, but they
      would need some alteration in their contents. The last four guidelines did not
      achieve a good score and therefore could not be considered for use in dental
      practice. In conclusion, more high-quality dental guidelines should be developed
      to support common dental procedures using standardized quality criteria in order
      to appropriately implement the evidence-based process into dental practice.
      Furthermore, the AGREE instrument may help dental practitioners objectively
      assess the quality of clinical guidelines.

PMID- 18346692
TI  - Little evidence of effectiveness for interventions aimed at preventing oral
      leukoplakia from becoming malignant.

PMID- 18346693
TI  - How effective is bone augmentation in implant treatment.

PMID- 18346694
TI  - Mouthrinses and dentifrices are effective antigingivitis and antiplaque agents.

PMID- 18346695
TI  - High fluoride concentration in drinking water may increase the prevalence and
      severity of dental fluorosis, and decrease occurrence of caries.

PMID- 18346696
TI  - Does exposure to fluoridated water during the crown completion and maturation
      phases of permanent first molars decrease pit and fissure caries?

PMID- 18346697
TI  - TMJ closed lock symptoms improve, regardless of intervention.

PMID- 18346698
TI  - Age and smoking status are associated with tooth loss during long-term supportive
      periodontal therapy in Brazilian patients.

PMID- 18346699
TI  - When primary molar lesions are cavitated into dentin, glass ionomer has similar 2
      year survival to resin composite as a restorative material when using the "ART"
      technique.

PMID- 18346700
TI  - Administration of intravenous antibiotics immediately before extraction of wisdom
      teeth lowers the rate of postsurgical infections.

PMID- 18346701
TI  - Survival of dental implants supporting single-unit prostheses may be related to
      location.

PMID- 18346702
TI  - Insufficient evidence for the efficacy of MRI for diagnosing TMJ disorder.

PMID- 18346703
TI  - Periodontitis low-susceptible subjects receiving regular primary prevention do
      not develop periodontitis.

PMID- 18346704
TI  - Swedish children with ADHD do not have a higher experience of dental caries
      compared to children without an ADHD diagnosis, in spite of showing poor dietary
      and oral hygiene patterns.

PMID- 18346705
TI  - Genetic factors appear to contribute substantially to dental caries
      susceptibility, and may also independently mediate sucrose sweetness preference.

PMID- 18346706
TI  - Third-molar extraction may increase relative risk for temporomandibular
      disorders.

PMID- 18346707
TI  - Posterior unilateral crossbite does not appear to be a risk factor for TMJ
      clicking in young adolescents.

PMID- 18346710
TI  - Protein carbonyl levels in serum and gingival crevicular fluid in patients with
      chronic periodontitis.
AB  - OBJECTIVE: Evidence reveals the role of reactive oxygen species (ROS) in many
      pathologies including periodontitis. Protein carbonylation is the most widely
      used biomarker for oxidative damage to proteins, and reflects cellular damage
      induced by ROS. In this study protein carbonyl (PC) levels in serum and gingival
      crevicular fluid (GCF) in patients with chronic periodontitis (CP) was evaluated.
      MATERIALS AND METHODS: Thirty-three patients with CP and 24 healthy controls were
      included in the study. Following the clinical measurements and samplings, total
      protein levels in serum and GCF were determined by Bradford method, and serum and
      GCF PC levels were measured by modified Levine method. RESULTS: PC levels in
      serum and GCF were significantly higher in the CP group compared to the control
      group (p<0.05). In all subjects, serum and GCF PC levels showed statistically
      significant positive correlations with all clinical parameters (p<0.05).
      CONCLUSIONS: The results suggest that both systemic and local/periodontal protein
      carbonylation increase in CP compared to health and that elevated levels of PCs
      may be a sign of oxidative damage in periodontitis and correlate well with the
      periodontal status.

PMID- 18346711
TI  - MicroRNA expression profiling of the developing murine molar tooth germ and the
      developing murine submandibular salivary gland.
AB  - Using microarrays, miRNA expression profiles have been established at selected
      times during development (E15.5, P0 and P5) of the murine first molar mandibular
      tooth germ and the right submandibular salivary gland (E15.5, P0, P5 and P25).
      Microarray data was validated using real-time PCR, also facilitating RT-PCR
      profiling of nine selected miRNAs. In general, good agreement between microarray
      data and real-time PCR data was found. Further, miRNA expression profiles of
      foetal and adult liver were also investigated, and found to agree with published
      data. In tooth germ and salivary gland up to 88 different miRNAs were detected.
      In all tissues examined miRNA expression was highly dynamic; miRNA profiles
      changing extensively with time of development. Additionally, the expression of
      some miRNAs was tissue-specific. Bioinformatic analysis of clusters of miRNAs was
      attempted using the miRGate software, the results suggesting miRNAs to be
      involved in the regulation of essential developmental processes, e.g.,
      epithelical cell proliferation, mesodermal cell fate determination and salivary
      gland morphogenesis.

PMID- 18346712
TI  - Cognitive-behavioural emotion writing tasks: a controlled trial of multiple
      processes.
AB  - We report on a controlled trial of three structured writing paradigms that engage
      the writer with cognitive-behavioural emotion-processes: exposure, devaluation,
      and benefit-finding. University students (N=198) wrote once a week for three
      weeks about their most upsetting experience. The long-term effects of these
      structured writing procedures were compared to an unstructured emotion writing
      condition and control. Outcomes indicated that exposure writing sped the
      reduction of intrusive and avoidant symptoms, while benefit-finding writing
      increased reports of positive growth. Results suggest the use of these paradigms
      to study emotion-processing mechanisms and, potentially, in practice to enhance
      coping in process-specific ways.

PMID- 18346713
TI  - An insight into the pharmacophores of phosphodiesterase-5 inhibitors from
      synthetic and crystal structural studies.
AB  - Selective inhibitors of cyclic nucleotide phosphodiesterase-5 (PDE5) have been
      used as drugs for treatment of male erectile dysfunction and pulmonary
      hypertension. An insight into the pharmacophores of PDE5 inhibitors is essential
      for development of second generation of PDE5 inhibitors, but has not been
      completely illustrated. Here we report the synthesis of a new class of the
      sildenafil derivatives and a crystal structure of the PDE5 catalytic domain in
      complex with 5-(2-ethoxy-5-(sulfamoyl)-3-thienyl)-1-methyl-3-propyl-1,6-dihydro
      7H-pyrazolo[4,3-d]pyrimidin-7-one (12). Inhibitor 12 induces conformational
      change of the H-loop (residues 660-683), which is different from any of the known
      PDE5 structures. The pyrazolopyrimidinone groups of 12 and sildenafil are well
      superimposed, but their sulfonamide groups show a positional difference of as
      much as 1.5A. The structure-activity analysis suggests that a small hydrophobic
      pocket and the H-loop of PDE5 are important for the inhibitor affinity, in
      addition to two common elements for binding of almost all the PDE inhibitors: the
      stack against the phenylalanine and the hydrogen bond with the invariant
      glutamine. However, the PDE5-12 structure does not provide a full explanation to
      affinity changes of the inhibitors. Thus alternatives such as conformational
      change of the M-loop are open and further structural study is required.

PMID- 18346714
TI  - STI571/doxorubicin concentration-dependent switch for diverse caspase actions in
      CML cell line K562.
AB  - We examined the response of the apoptosis-reluctant CML cell line K562 to
      doxorubicin alone or in combination with the tyrosine kinase inhibitor STI571. We
      found that at clinically relevant concentrations, doxorubicin induced
      differentiation and senescence, but did not induce apoptosis. Doxorubicin induced
      G(2)/M arrest and mitochondrial transmembrane potential dissipation.
      Interestingly, drug-induced differentiation could be diminished by caspase
      inhibitors. STI571 caused a graded response characterized by differentiation at
      low concentrations and apoptosis at higher. STI571 was not observed to induce
      senescence. Combination of STI571 and caspase inhibitors protected cells from
      apoptosis but did not influence differentiation. The diverse mode of action of
      both drugs contributed to the response observed during combination treatment. An
      additive effect on proliferation was obtained. The mechanisms contributing to
      inhibition of cellular proliferation were complex and strongly dependent on the
      applied drug concentrations. Differentiation or apoptosis were enhanced by
      combined treatment only in narrow ranges of concentrations. CONCLUSION: DOX and
      STI571 along diverse mechanisms contributed to elevated levels of activated
      caspases which might be then responsible for a switch from differentiation to
      apoptosis.

PMID- 18346715
TI  - Neurogenic development of the auditory areas of the midbrain and diencephalon in
      the Xenopus laevis and evolutionary implications.
AB  - To study whether the core-versus-shell pattern of neurogenesis occurred in the
      mesencephalic and diencephalic auditory areas of amniotes also appears in the
      amphibian, [(3)H]-thymidine was injected into tadpoles at serial developmental
      stages of Xenopus laevis. Towards the end of metamorphism, [(3)H]-thymidine
      labeling was examined and led to two main observations: 1) neuron generation in
      the principal nucleus (Tp) started at stage 50, and peaked at stage 53, whereas
      it began at stage 48.5, and peaked around stage 49 in the other two mesencephalic
      auditory areas, the laminar nucleus (Tl) and the magnocellular nucleus (Tmc). 2)
      Neuron generation appeared at stage 40, and peaked around stage 52 in the
      posterior thalamic nucleus (P) and the central thalamic nucleus (C). Our study
      revealed that, like the cores of mesencephalic auditory nuclei in amniotes, Tp
      showed differences from Tl and Tmc in the onset and the peak of neurogenesis.
      However, such differences did not occur in the P and C. Our neurogenetic data
      were consistent with anatomical and physiological reports indicating a clear
      distinction between the mesencephalic, but not the diencephalic auditory areas of
      the amphibian. Our data are helpful to get insights into the organization of
      auditory nuclei and its evolution in vertebrates.

PMID- 18346716
TI  - Cholecystokinin-33 is more effective than cholecystokinin-8 in inhibiting food
      intake and in stimulating the myenteric plexus and dorsal vagal complex.
AB  - We compared the abilities of cholecystokinin-33 (CCK-33) and CCK-8 to reduce food
      intake and to activate feeding-related areas of the nervous system. (1) Overnight
      food-deprived rats were presented with a 10% sucrose solution, and intake was
      measured at 5-min intervals throughout a 90-min test beginning immediately after
      intraperitoneal injections of 1, 3, or 5 nMol/kg of CCK-33, CCK-8, or the vehicle
      control. In the initial 20 min (first meal), both peptides were equally
      effective, producing large reductions of food intake. Thereafter, however, CCK-33
      was more effective than CCK-8, producing much more sustained reductions. Overall,
      both peptides reduced total food intake, but CCK-33 was more effective than CCK
      8. (2) Possible roles for the myenteric plexus of the duodenum and the dorsal
      vagal complex (DVC) of the brainstem in the differential satiety effects of CCK
      33 and CCK-8 were examined by quantifying CCK-33- and CCK-8-stimulated Fos-like
      immunoreactivity (Fos-LI) in each site. Consistent with the greater ability of
      CCK-33 to produce sustained inhibitions of food intake, CCK-33 produced more Fos
      LI than CCK-8 in nearly every section of the sampled sites. The results
      demonstrate: (1) Different forms of CCK have different efficacies in reducing
      food intake; (2) CCK-33 produces a much more prolonged satiety action than CCK-8;
      and (3) the myenteric plexus and DVC may play roles in these differential satiety
      actions.

PMID- 18346717
TI  - The Amadori rearrangement as key reaction for the synthesis of
      neoglycoconjugates.
AB  - The Amadori rearrangement was introduced as a key step for the conjugation of
      carbohydrate moieties with suitable amines such as aliphatic amines and amino
      acid derivatives. The rearrangement products were further transformed into the
      corresponding 1-N,2-O cyclic carbamates employing triphosgene to obtain
      anomerically stable glycoconjugates. The reaction conditions were probed on a
      model substrate, 3,5-di-O-benzyl-alpha,beta-d-glucofuranose and further applied
      to d-glycero-d-gulo-heptose, which gave 'd-gluco-conjugates' in the alpha
      anomeric form exclusively in high isolated yields.

PMID- 18346718
TI  - Immobilization of glucoamylase by adsorption on carbon supports and its
      application for heterogeneous hydrolysis of dextrin.
AB  - Glucoamylase (GA) was immobilized by adsorption on carbon support: on Sibunit, on
      bulk catalytic filamentous carbon (bulk CFC) and on activated carbon (AC). This
      was used to prepare heterogeneous biocatalysts for the hydrolysis of starch
      dextrin. The effect of the texture characteristics and chemical properties of the
      support surface on the enhancement of the thermal stability of the immobilized
      enzyme was studied, and the rates of the biocatalyst's thermal inactivation at 65
      80 degrees C were determined. The thermal stability of glucoamylase immobilized
      on different carbon supports was found to increase by 2-3 orders of magnitude in
      comparison with the soluble enzyme, and decrease in the following order: GA on
      Sibunit>GA on bulk CFC>GA on AC. The presence of the substrate (dextrin) was
      found to have a significant stabilizing effect. The thermal stability of the
      immobilized enzyme was found to increase linearly when the concentration of
      dextrin was increased from 10 wt/vol % to 50 wt/vol %. The total stabilization
      effect for glucoamylase immobilized on Sibunit in concentrated dextrin solutions
      was about 10(5) in comparison with the enzyme in a buffer solution. The developed
      biocatalyst, 'Glucoamylase on Sibunit' was found to have high operational
      stability during the continuous hydrolysis of 30-35 wt/vol % dextrin at 60
      degrees C, its inactivation half-time (t1/2) exceeding 350 h. To improve the
      starch saccharification productivity, an immersed vortex reactor (IVR) was
      designed and tested in the heterogeneous process with the biocatalyst
      'Glucoamylase on Sibunit'. The dextrin hydrolysis rate, as well as the process
      productivity in the vortex reactor, was found to increase by a factor of 1.2-1.5
      in comparison with the packed-bed reactor.

PMID- 18346719
TI  - Preparation and reactions of sugar azides with alkynes: synthesis of sugar
      triazoles as antitubercular agents.
AB  - 5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction
      of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with
      NaN3 in DMF. The intermediate 5-azido-5-deoxy glycofuranoses on 1,3-cycloaddition
      with different alkynes in the presence of CuSO4 and sodium ascorbate gave the
      corresponding sugar triazoles in very good yields. The synthesized sugar
      triazoles were evaluated for their antitubercular activity against Mycobacterium
      tuberculosis H37Rv, where one of the compounds displayed mild antitubercular
      activity in vitro with MIC 12.5 microg/mL.

PMID- 18346720
TI  - The chemical structure and genetic locus of Campylobacter jejuni CG8486 (serotype
      HS:4) capsular polysaccharide: the identification of 6-deoxy-D-ido-heptopyranose.
AB  - In line with our on-going efforts to create a multivalent anti-Campylobacter
      jejuni vaccine based on its capsule polysaccharides (CPSs), we report here the
      chemical structure and the genetic locus of the CPS produced by C. jejuni strain
      CG8486, which belongs to the serotype HS:4 CPS complex. C. jejuni CG8486 CPS was
      observed to be composed of approximately 17 disaccharide repeating blocks of 4
      substituted N-acetyl-beta-D-glucopyranosamine and 3-substituted 6-deoxy-beta-D
      ido-heptopyranose. A small number of 6-deoxy-beta-D-ido-heptopyranose units were
      observed to carry O-methyl phosphoramidate moieties at the O-2 or O-7 position.
      The gene content and organization of the CPS locus of C. jejuni CG8486 were
      comparable to those of C. jejuni strains NCTC 11168 and 81-176, but several
      CG8486 CPS genes were observed to be more divergent from those present in the CPS
      loci of NCTC 11168 and 81-176 CPS, which indicated that there are genetic
      characteristics specific to the C. jejuni HS:4 CPS complex. The efficacy of a
      glycoconjugate vaccine based on C. jejuni CG8486 CPS is presently being tested in
      an animal model, the results of which will be presented in future communications.

PMID- 18346721
TI  - Computational analyses of the conformational itinerary along the reaction pathway
      of GH94 cellobiose phosphorylase.
AB  - GH94 cellobiose phosphorylase (CBP) catalyzes the phosphorolysis of cellobiose
      into alpha-D-glucose 1-phosphate (G1P) and D-glucose with inversion of anomeric
      configuration. The complex crystal structure of CBP from Cellvibrio gilvus had
      previously been determined; glycerol, glucose, and phosphate are bound to
      subsites -1, +1, and the anion binding site, respectively. We performed
      computational analyses to elucidate the conformational itinerary along the
      reaction pathway of this enzyme. autodock was used to dock cellobiose with its
      glycon glucosyl residue in various conformations and with its aglycon glucosyl
      residue in the low-energy 4C1 conformer. An oxocarbenium ion-like glucose
      molecule mimicking the transition state was also docked. Based on the clustering
      analysis, docked energies, and comparison with the crystallographic ligands, we
      conclude that the reaction proceeds from 1S3 as the pre-transition state
      conformer (Michaelis complex) via E3 as the transition state candidate to 4C1 as
      the G1P product conformer. The predicted reaction pathway of the inverting
      phosphorylase is similar to that proposed for the first-half glycosylation
      reaction of retaining cellulases, but is different from those for inverting
      cellulases. NAMD was used to simulate molecular dynamics of the enzyme. The 1S3
      pre-transition state conformer is highly stable compared with other conformers,
      and a conformational change from 4C1 to 1,4B was observed.

PMID- 18346722
TI  - Candida albicans cell wall comprises a branched beta-D-(1-->6)-glucan with beta-D
      (1-->3)-side chains.
AB  - The structure of immunogenic and immunomodulatory cell wall glucans of Candida
      albicans is commonly interpreted in terms of a basic polysaccharide consisting of
      a beta-D-(1-->3)-linked glucopyranosyl backbone possessing beta-D-(1-->6)-linked
      side chains of varying distribution and length. This proposed molecular
      architecture has been re-evaluated by the present study on the products of
      selective enzymolysis of insoluble C. albicans glucan particles (GG). High
      resolution 1H (400 and 700 MHz) and 13C (100 and 175 MHz) NMR analyses were
      performed on a soluble beta-glucan preparation (GG-Zym) obtained by GG digestion
      with endo-beta-D-(1-->3)-glucanase and on its high- (Pool 1) and low-molecular
      weight (Pool 2) sub-fractions. The resonances typical of uniformly beta-D-(1-->6)
      and beta-D-(1-->3)-linked linear glucans, together with additional multiplets
      assigned to short-chain oligoglucosides, were detected in GG-Zym. Pool 1 (46.3+/
      6.4% of GG-Zym content) consisted of beta-D-(1-->6)-linked glucopyranosyl
      polymers, with short beta-D-(1-->3)-branched side chains of 2.20+/-0.02 units
      (branching degree (DB)=0.14+/-0.03). Pool 2 was a mixture of glucose and linear
      short-chain beta-D-(1-->3)-oligoglucosides. Further digestion of Pool 1 by beta-D
      (1-->6)-glucanase yielded a mixture of glucose and short beta-D-(1-->6)-linked,
      either linear or beta-D-(1-->3,6) branched, oligomers. These endoglucanase
      digestion patterns were consistent with the presence in C. albicans cell wall
      glucans of beta-D-(1-->6)-linked glucopyranosyl backbones possessing beta-D-(1-
      >3)-linked side chains, a structure very close to that of beta-D-(1-->6)-glucan
      from Saccharomyces cerevisiae yeast. This finding may provide the grounds for
      further elucidation of the cell wall structure and a better understanding of the
      biological properties of C. albicans beta-glucans.

PMID- 18346723
TI  - Mechanistic differences among retaining disaccharide phosphorylases: insights
      from kinetic analysis of active site mutants of sucrose phosphorylase and
      alpha,alpha-trehalose phosphorylase.
AB  - Sucrose phosphorylase utilizes a glycoside hydrolase-like double displacement
      mechanism to convert its disaccharide substrate and phosphate into alpha-d
      glucose 1-phosphate and fructose. Site-directed mutagenesis was employed to
      characterize the proposed roles of Asp(196) and Glu(237) as catalytic nucleophile
      and acid-base, respectively, in the reaction of sucrose phosphorylase from
      Leuconostoc mesenteroides. The side chain of Asp(295) is suggested to facilitate
      the catalytic steps of glucosylation and deglucosylation of Asp(196) through a
      strong hydrogen bond (23 kJ/mol) with the 2-hydroxyl of the glucosyl oxocarbenium
      ion-like species believed to be formed in the transition states flanking the beta
      glucosyl enzyme intermediate. An assortment of biochemical techniques used to
      examine the mechanism of alpha-retaining glucosyl transfer by Schizophyllum
      commune alpha,alpha-trehalose phosphorylase failed to provide evidence in support
      of a similar two-step catalytic reaction via a covalent intermediate. Mutagenesis
      studies suggested a putative active-site structure for this trehalose
      phosphorylase that is typical of retaining glycosyltransferases of fold family GT
      B and markedly different from that of sucrose phosphorylase. While ambiguity
      remains regarding the chemical mechanism by which the trehalose phosphorylase
      functions, the two disaccharide phosphorylases have evolved strikingly different
      reaction coordinates to achieve catalytic efficiency and stereochemical control
      in their highly analogous substrate transformations.

PMID- 18346724
TI  - Synthesis of 8-azidooctyl glycoside derivatives of the O-chain repeating unit of
      Escherichia coli O9a lipopolysaccharide and a methylated analog.
AB  - Described is the synthesis of 8-azidooctyl glycoside derivatives of the
      Escherichia coli serotype O9a O-chain tetrasaccharide repeating unit and the
      terminal tetrasaccharide motif in this polysaccharide, which contains a methyl
      group on O-3 of the distal mannopyranose residue. The assembly of these compounds
      involved the sequential addition of monosaccharide residues from the reducing to
      the nonreducing end of the molecule using glycosyl trichloroacetimidate donors.
      Both compounds were initially prepared as p-methoxyphenyl glycosides, which were
      converted to the corresponding 8-azidooctyl derivatives at a late stage in the
      synthesis.

PMID- 18346725
TI  - Cryopreservation of goldfish fins and optimization for field scale cryobanking.
AB  - When gametes and embryos are not available, cryobanking of somatic tissues is one
      possibility to keep a genetic record of fish valuables in a context of
      biodiversity conservation and animal breeding management. Cryopreservation of
      whole fin pieces would be more advantageous than the commonly used
      cryopreservation of cells after fin culture, as it would allow extensive sampling
      without immediate need for laboratory facilities. The objective of this work was
      to assess the cryopreservation ability of fin pieces from goldfish (Carassius
      auratus) and to test whether a laboratory procedure could be adapted to field
      conditions. Caudal fin explants were cryopreserved in culture medium with 125mM
      sucrose and 10% Me(2)SO. After 14days of culture, the frozen-thawed explants
      showed the same cell growth rate and grew the same somatic cell number as the
      fresh ones. Cells proliferated inside and around the explants as shown by BrdU
      labeling. Neither the size of the fin pieces nor the freezer type, -70 degrees C
      upright or -20 degrees C chest, influenced the outcome of cryopreservation. Fin
      pieces were stored 4days at 4 degrees C in dry conditions prior to
      cryopreservation without alteration of the fin explant culture success. This
      study demonstrated that field collecting of goldfish fin pieces is possible as
      whole fin pieces can be stored in standard fridge or be shipped at subzero
      temperature before they are frozen into a plain -20 degrees C chest freezer.
      After incorporation in cryobanks in liquid nitrogen, thawed fin pieces reliably
      produce somatic cells in cell culture conditions.

PMID- 18346726
TI  - Transcriptional profiling of the rat frontal cortex following administration of
      the mGlu5 receptor antagonists MPEP and MTEP.
AB  - The development of selective type 5 metabotropic glutamate receptor (mGlu5)
      antagonists, such as 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and 3-[(2-methyl
      1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP), has revealed an important role for
      these receptors in various disorders of the nervous system including depression,
      anxiety, epilepsy, Parkinson's disease, drug addiction, and alcoholism. In this
      study, we used microarray technology to examine changes in gene expression
      induced by repeated administration of the mGlu5 antagonists MPEP and MTEP. Male
      Wistar rats (n=5 per treatment group) were administered MPEP (10 mg/kg), MTEP (10
      mg/kg) or vehicle intraperitoneally twice daily for 5 days. Approximately 30 min
      following the final drug administration, rats were sacrificed and frontal
      cortices were then dissected and examined for changes in gene expression by cDNA
      microarray analysis. Changes in gene expression with p-values less than 0.01 were
      considered to be statistically significant. The expression of 63 genes was
      changed by both MPEP and MTEP, with 58 genes down-regulated and 5 genes up
      regulated. Quantitative PCR verified the magnitude and direction of change in
      expression of 9 of these genes (r2=0.556, p=0.017). Pathway analysis revealed
      that many of the biological processes altered by repeated MPEP and MTEP treatment
      were related to ATP synthesis, hydrolase activity, and signaling pathways
      associated with mitogen-activated protein kinase (MAPK). Our results demonstrate
      diverse effects of MPEP and MTEP gene expression in the frontal cortex, and these
      results may help elucidate the mechanisms by which these compounds produce
      beneficial effects in animal models of various disorders of the central nervous
      system.

PMID- 18346727
TI  - The homeostasis of iron and suppression of HO-1 involved in the protective
      effects of nimodipine on neurodegeneration induced by aluminum overloading in
      mice.
AB  - Aluminum intoxication can cause damage to the cognitive function and
      neurodegenerative diseases. In the present study, we investigated the role of
      iron homeostasis and heme oxygenase-1 (HO-1) expression in the protective effects
      of nimodipine on the neurodegeneration induced by aluminum overloading in mice. 2
      microl of 0.25% aluminum chloride solution was intracerebroventricularly injected
      once a day for five days to induce the neurodegeneration of mice. Nimodipine was
      administered by intragastric gavage (80 mg/kg per day) for 30 days. We observed
      that nimodipine could improve the performance of behavior test related to the
      learning and memory function and ameliorate pathological changes of hippocampi
      caused by aluminum. Results of western blot, immunohistochemistry study,
      biochemical test and inductively coupled plasma-atomic emission spectrometry
      showed that nimodipine could suppress the increased expression of HO-1 protein,
      and decrease the elevation of both HO activity and iron level in hippocampi,
      induced by aluminum overloading. These results indicate that nimodipine can
      suppress the neurodegenerative development induced by aluminum overloading and
      the mechanism of its action is at least partly related to keeping the homeostasis
      of iron through blunting the expression of HO-1 in hippocampus.

PMID- 18346728
TI  - A novel selective peroxisome proliferator-activator receptor-gamma modulator
      SPPARgammaM5 improves insulin sensitivity with diminished adverse cardiovascular
      effects.
AB  - The use of the thiazolidinedione insulin sensitizers rosiglitazone and
      pioglitazone for the treatment of type 2 diabetes mellitus in recent years has
      proven to be effective in helping patients resume normal glycemic control.
      However, their use is often associated with undesirable side effects including
      peripheral edema, congestive heart failure and weight gain. Here, we report the
      identification and characterization of a novel selective PPARgamma modulator,
      SPPARgammaM5 ((2S)-2-(2-chloro-5-{[3-(4-chlorophenoxy)-2-methyl-6
      (trifluoromethoxy)-1H-indol-1-yl]methyl} phenoxy)propionic acid), which has
      notable insulin sensitizing properties and a superior tolerability profile to
      that of rosiglitazone. SPPARgammaM5 is a potent ligand of human PPARgamma with
      high selectivity versus PPARalpha or PPARdelta in receptor competitive binding
      assays. In cell-based transcriptional activation assays, SPPARgammaM5 was a
      potent partial agonist of human PPARgamma in comparison to the PPARgamma full
      agonist rosiglitazone. Compared to rosiglitazone or the PPARgamma full agonist
      COOH (2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid), SPPARgammaM5
      induced an attenuated PPARgamma-regulated gene expression profile in fully
      differentiated 3T3-L1 adipocytes and white adipose tissue of chronically treated
      db/db mice. SPPARgammaM5 treatment also reduced the insulin resistance index by
      homeostasis model assessment (HOMA), suggesting an improvement in insulin
      resistance in these db/db mice. Treatment of obese Zucker rats with either
      rosiglitazone or SPPARgammaM5 resulted in an improvement in selected parameters
      that serve as surrogate indicators of insulin resistance and hyperlipidemia.
      However, unlike rosiglitazone, SPPARgammaM5 did not cause significant fluid
      retention or cardiac hypertrophy in these rats. Thus, compounds such as
      SPPARgammaM5 may offer beneficial effects on glycemic control with significantly
      attenuated adverse effects.

PMID- 18346729
TI  - Somatic cell nuclear transfer: infinite reproduction of a unique diploid genome.
AB  - In mammals, a diploid genome of an individual following fertilization of an egg
      and a spermatozoon is unique and irreproducible. This implies that the generated
      unique diploid genome is doomed with the individual ending. Even as cultured
      cells from the individual, they cannot normally proliferate in perpetuity because
      of the "Hayflick limit". However, Dolly, the sheep cloned from an adult mammary
      gland cell, changes this scenario. Somatic cell nuclear transfer (SCNT) enables
      us to produce offspring without germ cells, that is, to "passage" a unique
      diploid genome. Animal cloning has also proven to be a powerful research tool for
      reprogramming in many mammals, notably mouse and cow. The mechanism underlying
      reprogramming, however, remains largely unknown and, animal cloning has been
      inefficient as a result. More momentously, in addition to abortion and fetal
      mortality, some cloned animals display possible premature aging phenotypes
      including early death and short telomere lengths. Under these inauspicious
      conditions, is it really possible for SCNT to preserve a diploid genome?
      Delightfully, in mouse and recently in primate, using SCNT we can produce nuclear
      transfer ES cells (ntES) more efficiently, which can preserve the eternal
      lifespan for the "passage" of a unique diploid genome. Further, new somatic
      cloning technique using histone-deacetylase inhibitors has been developed which
      can significantly increase the previous cloning rates two to six times. Here, we
      introduce SCNT and its value as a preservation tool for a diploid genome while
      reviewing aging of cloned animals on cellular and individual levels.

PMID- 18346730
TI  - Topical interleukin-1 receptor antagonist inhibits inflammatory cell infiltration
      into the cornea.
AB  - Interleukin (IL)-1alpha and beta are important modulators of many functions of
      corneal epithelial and stromal cells that occur following injury to the cornea,
      including the influx of bone marrow-derived inflammatory cells into the stroma
      attracted by chemokines released from the stroma and epithelium. In this study,
      we examined the effect of topical soluble IL-1 receptor antagonist on bone marrow
      derived cell influx following corneal epithelial scrape injury in a mouse model.
      C57BL/6 mice underwent corneal epithelial scrape followed by application of IL-1
      receptor antagonist (Amgen, Thousand Oaks, CA) at a concentration of 20 mg/ml or
      vehicle for 24 h prior to immunocytochemical detection of marker CD11b-positive
      cells into the stroma. In two experiments, topical IL-1 receptor antagonist had a
      marked effect in blocking cell influx. For example, in experiment 1, topical IL-1
      receptor antagonist markedly reduced detectible CD11b-positive cells into the
      corneal stroma at 24h after epithelial injury compared with the vehicle control
      (3.5+/-0.5 (standard error of the mean) cells/400x field and 13.9+/-1.2
      cells/400x field, respectively, p<0.01). A second experiment with a different
      observer performing cell counting had the same result. Thus, the data demonstrate
      conclusively that topical IL-1 receptor antagonist markedly down-regulates CD-11b
      positive monocytic cell appearance in the corneal stroma. Topical IL-1 receptor
      antagonist could be an effective adjuvant for clinical treatment of corneal
      conditions in which unwanted inflammation has a role in the pathophysiology of
      the disorder.

PMID- 18346731
TI  - Comment on: "High concentration of zinc in sub-retinal pigment epithelial
      deposits" (Lengyel et al.) (Exp. Eye Res. 772-780, 84/4, 2007).

PMID- 18346732
TI  - Combined treatment with atorvastatin and minocycline suppresses severity of EAE.
AB  - Multiple sclerosis (MS) is the most common inflammatory demyelinating disorder of
      the central nervous system (CNS). An approach to improve MS treatment is to
      identify a rational combination of new medications or existing therapies that
      impact different aspects of the disease process. Statins are effective in the
      treatment of MS animal models and are promising candidates for future treatment.
      Minocycline ameliorates clinical severity of experimental autoimmune
      encephalomyelitis (EAE) and exhibits several anti-inflammatory and
      neuroprotective activities. In this study, we tested whether the combination of
      these two drugs could produce beneficial effects in EAE mice immunized with
      myelin oligodendrocyte protein (MOG). Our findings show that combined treatment,
      compared to using the medications alone, resulted in a significant reduction in
      disease severity, in both the acute and chronic phases of the disease, along with
      attenuation of inflammation, demyelination and axonal loss. Stereological
      analysis revealed that the combined treatment significantly guarded against
      neuroinflammation and neurodegeneration. Moreover, a significant suppression of
      anti-MOG antibody production in animals treated with the two medications was
      found. In conclusion, our findings prove that this combination of drugs is
      neuroprotective and suppresses the severity of EAE. Furthermore, this
      pharmacological approach appears to be promising as a future therapeutic strategy
      to control MS.

PMID- 18346733
TI  - Injection of neural progenitor cells improved learning and memory dysfunction
      after cerebral ischemia.
AB  - Accumulating evidence indicates that stem cells have the ability to improve
      neurological deficits seen after cerebral ischemia. However, the effects of
      neural progenitor cells (NPCs) on cerebral ischemia-induced learning and memory
      dysfunction remain to be clarified. The purpose of the present study was to
      determine whether the injection of exogenous NPCs could prevent learning and
      memory dysfunction after cerebral ischemia. Sustained cerebral ischemia was
      produced by the injection of 700 microspheres into the right hemisphere of each
      rat. We demonstrated that injection of NPCs into the hippocampus at 10 min after
      the induction of cerebral ischemia reduced prolongation of the escape latency
      seen in acquisition and retention tests of the water maze task on Days 12-28
      after cerebral ischemia. Injection of NPCs partially attenuated the decrease in
      viable areas of the ipsilateral hemisphere on Day 28 after the cerebral ischemia.
      We also demonstrated that injection of NPCs prevented the decrease in the level
      of BDNF seen at the early period after cerebral ischemia. These results suggest
      that the injection of exogenous NPCs into the hippocampus can prevent cerebral
      ischemia-induced learning and memory dysfunction, possibly through maintenance of
      the BDNF level.

PMID- 18346734
TI  - AAV2-mediated gene transfer of GDNF to the striatum of MPTP monkeys enhances the
      survival and outgrowth of co-implanted fetal dopamine neurons.
AB  - Neural transplantation offers the potential of treating Parkinson's disease by
      grafting fetal dopamine neurons to depleted regions of the brain. However,
      clinical studies of neural grafting in Parkinson's disease have produced only
      modest improvements. One of the main reasons for this is the low survival rate of
      transplanted neurons. The inadequate supply of critical neurotrophic factors in
      the adult brain is likely to be a major cause of early cell death and restricted
      outgrowth of fetal grafts placed into the mature striatum. Glial derived
      neurotrophic factor (GDNF) is a potent neurotrophic factor that is crucial to the
      survival, outgrowth and maintenance of dopamine neurons, and so is a candidate
      for protecting grafted fetal dopamine neurons in the adult brain. We found that
      implantation of adeno-associated virus type 2 encoding GDNF (AAV2-GDNF) in the
      normal monkey caudate nucleus induced overexpression of GDNF that persisted for
      at least 6 months after injection. In a 6-month within-animal controlled study,
      AAV2-GDNF enhanced the survival of fetal dopamine neurons by 4-fold, and
      increased the outgrowth of grafted fetal dopamine neurons by almost 3-fold in the
      caudate nucleus of MPTP-treated monkeys, compared with control grafts in the
      other caudate nucleus. Thus, the addition of GDNF gene therapy to neural
      transplantation may be a useful strategy to improve treatment for Parkinson's
      disease.

PMID- 18346735
TI  - Potential role of pyridoxal-5'-phosphate phosphatase/chronopin in epilepsy.
AB  - Changes in actin dynamics and pyridoxal-5'-phosphate (PLP) metabolisms are
      closely related to the pathophysiological profiles of the epileptic hippocampus.
      Recently, it has been reported that PLP phosphatase/chronophin (PLPP/CIN)
      directly dephosphorylates actin-depolymerizing factor (ADF)/cofilin as well as
      PLP. In the present study, therefore, we have investigated whether PLPP/CIN is
      linked to the dynamics of actin filament assembly and the excitability in the rat
      hippocampus. In control animals, pyridoxine chloride (PNP) treatment increased
      PLPP/CIN immunoreactivity only in astrocytes, which did not affect
      electrophysiological properties. Following status epilepticus, the PLPP/CIN
      protein level increased in granule cells and reactive astrocytes. These changes
      in PLPP/CIN protein level showed an inverse correlation with phospho-ADF
      (pADF)/cofilin levels and F-actin content. These changes were also accompanied by
      alterations in the excitability ratio and paired-pulse inhibition. Transduction
      of PLPP/CIN by Tat-PLPP/CIN showed similar effects on pADF/cofilin levels, F
      actin content and excitability ratio in normal animals. These findings suggest
      that PLPP/CIN-mediated actin dynamics may play an important role in the changes
      of morphological properties and excitability of the epileptic hippocampus.

PMID- 18346736
TI  - Leishmania (L.) amazonensis: fusion between parasitophorous vacuoles in infected
      bone-marrow derived mouse macrophages.
AB  - [Leishmania(L.)] amazonensis amastigotes reside in macrophages within spacious
      parasitophorous vacuoles (PVs) which may contain numerous parasites. After
      sporadic fusion events were detected by time-lapse cinemicrography, PV fusion was
      examined in two different models. In single infections, it was inferred from the
      reduction in PV numbers per cell. In a reinfection model, macrophages infected
      with unlabeled amastigotes were reinfected with GFP-transfected- or
      carboxyfluorescein diacetate succinimidyl ester-labeled parasites, and fusion was
      detected by the colocalization of labeled and unlabeled amastigotes in the same
      PVs. The main findings were: (1) as expected, fusion frequency increased with the
      multiplicity of infection; (2) most fusion events took place in the first 24h of
      infection or reinfection, prior to the multiplication of incoming parasites; (3)
      resident and incoming parasites multiplied at similar rates in fused PVs. The
      model should be useful in studies of parasite and host cell factors and
      mechanisms involved in PV fusogenicity.

PMID- 18346737
TI  - Loss of dsRNA-based gene silencing in Entamoeba histolytica: implications for
      approaches to genetic analysis.
AB  - The ability to regulate gene expression in the protozoan parasite Entamoeba
      histolytica is critical in determining gene function. We previously published
      that expression of dsRNA specific to E. histolytica serine threonine isoleucine
      rich protein (EhSTIRP) resulted in reduction of gene expression [MacFarlane,
      R.C., Singh, U., 2007. Identification of an Entamoeba histolytica serine,
      threonine, isoleucine, rich protein with roles in adhesion and cytotoxicity.
      Eukaryotic Cell 6, 2139-2146]. However, after approximately one year of
      continuous drug selection, the expression of EhSTIRP reverted to wild-type
      levels. We confirmed that the parasites (i) contained the appropriate dsRNA
      plasmid, (ii) were not contaminated with other plasmids, (iii) the drug
      selectable marker was functional, and (iv) sequenced the dsRNA portion of the
      construct. This work suggests that in E. histolytica long term cultivation of
      parasites expressing dsRNA can lead to the loss of dsRNA based silencing through
      the selection of "RNAi" negative parasites. Thus, users of the dsRNA silencing
      approach should proceed with caution and regularly confirm gene down regulation.
      The development and use of constructs for inducible expression of dsRNA may help
      alleviate this potential problem.

PMID- 18346738
TI  - Death by apoptosis in salivary glands of females of the tick Rhipicephalus
      sanguineus (Latreille, 1806) (Acari: Ixodidae).
AB  - The salivary glands of females of the tick Rhipicephalus sanguineus at three
      feeding stages: unfed, engorged, and at day three post-engorgement, were
      subjected to cytochemical methods of enzymatic analysis and cell viability.
      Comparing glands at these stages, was observed distinct staining patterns in
      cells of different types of acini, specially in degenerating types III, II, I,
      which were affected in this sequence by cell death. This study also revealed
      changes in: nuclei, staining intensity for acid phosphatase and ATPase
      activities, and permeability of the plasma membrane. Acid phosphatase activity
      was inversely proportional to that of ATPase, while ATPase activity was always
      proportional to membrane integrity. The glands of unfed females exhibited high
      metabolic activity and cells with intact nucleus and plasma membrane, suggesting
      that the presence of acid phosphatase detected in these individuals may
      participate in the normal physiology of some acini, as they were not undergoing
      degeneration. In acini I and II of engorged females, we observed cells with
      intact membranes, as well as changes characterized by nuclear changes, decrease
      in ATPase activity, and stronger acid phosphatase activity. At day three post
      engorgement, degeneration progressed to more advanced stages, loss of membrane
      integrity was observed in most cells (of some type I acini, most type II acini,
      and all type III acini), as well as prominent nuclear changes, decrease in ATPase
      activity, and intense acid phosphatase activity, resulting in apoptotic bodies.
      During the death of cells nuclear changes preceded cytoplasmic ones in the
      following sequence: nuclear changes, loss of ATPase activity, loss of integrity
      of the plasma membrane, increase in acid phosphatase activity, and formation of
      apoptotic bodies. The presence of acid phosphatase with a secondary role (late)
      during cell death, degrading final cell remnants, characterized this process in
      the glands of R. sanguineus females as atypical or non-classic apoptosis.

PMID- 18346739
TI  - Babesia divergens: identification and characterization of BdHSP-20, a small heat
      shock protein.
AB  - This study describes the identification and characterization of the Babesia
      divergens alpha-crystallin/small heat shock protein 20 (BdHSP-20). BdHSP-20 was
      recognized by the DG7 monoclonal antibody (DG7 mAb) originally produced by
      Precigout et al. [Precigout, E., Valentin, A., Carcy, B., Gorenflot, A.,
      Nakamura, K., Aikawa, M., Schrevel, J. 1993. Babesia divergens: characterization
      of a 17-kDa merozoite membrane protein. Experimental Parasitology 77, 425-434]
      against B. divergens merozoites. We used DG7 mAb to immunoscreen a B. divergens
      cDNA library to clone the gene encoding the small heat shock protein. Bdhsp-20 is
      a single copy gene interrupted by one intron. The deduced gene product (BdHSP-20)
      clearly belongs to the alpha-crystallin family and shows significant homology to
      Babesia bovis, Plasmodium falciparum and Toxoplasma gondii sHSPs, with the
      highest degree of sequence identity around the catalytic domain. Nutritient
      stress (serum depletion) treatment of the parasites induced the upregulation of
      BdHSP-20 gene expression observed by semi-quantitative PCR and
      immunoprecipitation. This regulation pattern suggests that BdHSP-20 could
      probably be of importance for parasite survival in the case of environmental
      stress. BdHSP-20 has previously been shown to be highly conserved among different
      strains and antibodies against the protein drastically reduce parasitemia in
      vitro.

PMID- 18346740
TI  - Activational effects of estradiol and dihydrotestosterone on social recognition
      and the arginine-vasopressin immunoreactive system in male mice lacking a
      functional aromatase gene.
AB  - In rodents, parts of the arginine-vasopressin (AVP) neuronal system are sexually
      dimorphic with males having more AVP-immunoreactive cells/fibers than females.
      This neuropeptide neuronal system is highly sensitive to steroids and has been
      proposed to play an important role in the processing of olfactory cues critical
      to the establishment of a social memory. We demonstrate here that gonadally
      intact male aromatase knockout (ArKO) mice, which cannot aromatize androgens into
      estrogens due to a targeted mutation in the aromatase gene, showed severe
      deficits in social recognition as well as a reduced AVP-immunoreactivity in
      several brain regions. To determine whether this reduction is due to a lack of
      organizational or activational effects of estrogens, we assessed social
      recognition abilities and AVP-immunoreactivity in male ArKO and wild-type (WT)
      mice when treated with estradiol benzoate (EB) in association with
      dihydrotestosterone propionate (DHTP) in adulthood. Adult treatment with EB and
      DHTP restored social recognition abilities in castrated ArKO males since they
      showed normal female-oriented ultrasonic vocalizations and were able to recognize
      an unfamiliar female using a habituation-dishabituation paradigm. Furthermore,
      adult treatment also restored AVP-immunoreactivity in the lateral septum of ArKO
      males to levels observed in intact WT males. These results suggest that social
      recognition in adulthood and stimulation of AVP expression in the adult mouse
      forebrain depend predominantly on the estrogenic metabolite of testosterone.
      Furthermore, our results are in line with the idea that the organization of the
      AVP system may depend on androgen or sex chromosomes rather than estrogens.

PMID- 18346741
TI  - Defining the neuroendocrine parameters of aggression.

PMID- 18346742
TI  - Ethical framework for gynecologic and obstetric care.

PMID- 18346743
TI  - Determination of LOX-1-ligand activity in mouse plasma with a chicken monoclonal
      antibody for ApoB.
AB  - Oxidized LDL (OxLDL) is implicated in endothelial dysfunction as well as the
      formation and progression of atherosclerosis. It has become evident that the
      atherogenic properties induced by OxLDL are mainly mediated via lectin-like OxLDL
      receptor-1 (LOX-1). Over the past decade, much research has been performed to
      investigate lipid metabolism and atherogenesis using genetically engineered mice.
      To understand the significance of OxLDL, methods to measure the levels of OxLDL
      in these experimental animals should be established. Utilizing a chicken
      monoclonal antibody technique, here, we generated anti-human ApoB antibodies that
      are able to recognize mouse VLDL/LDL. These antibodies were selected from single
      chain fragment of variable region (scFv) phage library constructed from chickens
      immunized with human LDL. One of these antibodies, HUC20, was reconstructed into
      IgY form. Immunohistochemical analysis revealed that this novel antibody
      specifically stains atherosclerotic lesions of ApoE-deficient mice, associated
      with Oil red O positive and macrophage-antigen-positive regions. Furthermore, in
      combination with recombinant LOX-1, a sandwich enzyme immunoassay was developed
      to measure the levels of LOX-1 ligands in mouse plasma. The sandwich enzyme
      immunoassay revealed a dramatic increase in the level of LOX-1 ligands in the
      plasma of ApoE-deficient mice fed high-fat diet, suggesting a link between the
      level of LOX-1-ligands and the progression of atherosclerosis in mice. Hence, the
      chicken anti-ApoB monoclonal antibody HUC20 developed here, could be a useful
      tool to analyze the role of ApoB-containing lipoprotein in atherogenesis in mice.

PMID- 18346744
TI  - Obese related effects of inflammatory markers and insulin resistance on increased
      carotid intima-media thickness in pre-pubertal children.

PMID- 18346745
TI  - Subject-specific hip geometry affects predicted hip joint contact forces during
      gait.
AB  - Hip loading affects bone remodeling and implant fixation. In this study, we have
      analyzed the effect of subject-specific modeling of hip geometry on muscle
      activation patterns and hip contact forces during gait, using musculoskeletal
      modeling, inverse dynamic analysis and static optimization. We first used
      sensitivity analysis to analyze the effect of isolated changes in femoral neck
      length (NL) and neck-shaft angle (NSA) on calculated muscle activations and hip
      contact force during the stance phase of gait. A deformable generic
      musculoskeletal model was adjusted incrementally to adopt a physiological range
      of NL and NSA. In a second similar analysis, we adjusted hip geometry to the
      measurements from digitized radiographs of 20 subjects with primary hip
      osteoarthrosis. Finally, we studied the effect of hip abductor weakness on muscle
      activation patterns and hip contact force. This analysis showed that differences
      in NL (41-74 mm) and NSA (113-140 degrees ) affect the muscle activation of the
      hip abductors during stance phase and hence hip contact force by up to three
      times body weight. In conclusion, the results from both the sensitivity and
      subject-specific analysis showed that at the moment of peak contact force,
      altered NSA has only a minor effect on the loading configuration of the hip.
      Increased NL, however, results in an increase of the three hip contact-force
      components and a reduced vertical loading. The results of these analyses are
      essential to understand modified hip joint loading, and for planning hip surgery
      for patients with osteoarthrosis.

PMID- 18346746
TI  - Simultaneous determination of traces of pyrethroids, organochlorines and other
      main plant protection agents in agricultural soils by headspace solid-phase
      microextraction-gas chromatography.
AB  - A solvent-free and simple method based on headspace solid-phase microextraction
      (HS-SPME) was developed in order to determine simultaneously 36 common pesticides
      and breakdown products (mostly pyrethroids and organochlorine compounds) in soil.
      The analysis was carried out by gas chromatography with micro-electron-capture
      detection (GC-microECD). As far as we know, this is the first study about the
      SPME of pyrethroid insecticides from soil. Factors such as extraction
      temperature, matrix modification by addition of water, salt addition (% NaCl) and
      fiber coating were considered in the optimization of the HS-SPME. To this end, a
      3 x 2(3-1) fractional factorial design was performed. The results showed that
      temperature and fiber coating were the most significant variables affecting
      extraction efficiency. A suitable sensitivity for all investigated compounds was
      achieved at 100 degrees C by extracting soil samples wetted with 0.5 mL of
      ultrapure water (0% NaCl) employing a polyacrylate (PA) coating fiber. Using the
      recommended extraction conditions with GC-microECD, a linear calibration could be
      achieved over a range of two orders of magnitude for both groups of analytes.
      Limits of detection (LODS) at the sub-ng g(-1) level were attained and relative
      standard deviations (RSDs) were found to be lower than 14% for both groups of
      pesticides. Matrix effects were investigated by the analysis of different soil
      samples fortified with the target compounds. The method accuracy was assessed and
      good recovery values (>70%, in most cases) were obtained. The method was also
      validated with a certified reference material (RTC-CRM818-050), which was
      quantified using a standard addition protocol. Finally, the proposed HS-SPME-GC
      microECD methodology was further applied to the screening of environmental soil
      samples for the presence of the target pesticides.

PMID- 18346747
TI  - Trace determination of organophosphorus pesticides in environmental samples by
      temperature-controlled ionic liquid dispersive liquid-phase microextraction.
AB  - This paper described a new approach for the determination of organophosphorus
      pesticides by temperature-controlled ionic liquid dispersive liquid-phase
      microextraction prior to high-performance liquid chromatography with ultraviolet
      detection. Methylparathion and phoxim, two of the typical organophosphorus
      pesticides, were used as the model analytes for the investigation of the
      development and application of the new microextraction method. 1-Hexyl-3
      methylimidazolium hexafluorophosphate [C6MIM][PF6] was used as the extraction
      solvent and the factors affecting the extraction efficiency such as the volume of
      [C6MIM][PF6], pH of working solutions, extraction time, centrifuging time,
      dissoluble temperature and salt effect were optimized. Under the optimal
      extraction conditions, methylparathion and phoxim exhibited good linear
      relationship in the concentration range of 1-100 ng mL(-1). The detection limits
      were 0.17 ng mL(-1) and 0.29 ng mL(-1), respectively. Precisions of proposed
      method (RSDs, n=6) were 2.5% and 2.7%, respectively. This proposed method was
      successfully applied in the analysis of four real environmental water samples and
      good spiked recoveries over the range of 88.2-103.6% were obtained. These results
      indicated that temperature-controlled ionic liquid dispersive liquid-phase
      microextraction had excellent application prospect in environmental field.

PMID- 18346748
TI  - Liquid chromatographic resolution of vigabatrin and its analogue gamma-amino
      acids on chiral stationary phases based on (+)-(18-crown-6)-2,3,11,12
      tetracarboxylic acid.
AB  - Racemic vigabatrin, an anticonvulsant drug used for the treatment of epilepsy,
      and its analogue gamma-amino acids were resolved without derivatization on liquid
      chromatographic chiral stationary phases (CSPs) based on (+)-(18-crown-6)
      2,3,11,12-tetracarboxylic acid. Between the two CSPs which contain 3 methylene
      unit or 11 methylene-unit spacer group, the latter was found to be greater than
      the former in the resolution of vigabatrin and its analogue gamma-amino acids,
      the separation, alpha, and the resolution factor, RS, for the resolution of
      vigabatrin on the latter being 1.91 and 4.57, respectively. The chromatographic
      behaviors for the resolution of vigabatrin and its analogue gamma-amino acids on
      the two CSPs were found to be dependent on the type and the content of organic
      and acidic modifiers in aqueous mobile phase.

PMID- 18346749
TI  - Comprehensive study of the parameters influencing the detection of organotin
      compounds by a pulsed flame photometric detector in sewage sludge.
AB  - An investigation of the operating conditions of a pulsed flame photometric
      detection (PFPD) system for the determination of organotin compounds (OTCs) in
      sewage sludge is reported. During the analyses, some spectral interferences were
      observed. For their elimination detector parameters such as gate delay and gate
      width were investigated. In addition, the applicability of three different
      internal standards was evaluated. Under optimised analytical conditions (gate
      delay 3 ms, gate width 2 ms, tripropyltin as internal standard) limits of
      detection (LOD) were determined. The LOD for butyltins ranged between 8 and 16 ng
      Sn g(-1), for phenyltins around 8 ng Sn g(-1) and for octyltins between 5 and 10
      ng Sn g(-1). Since there is no certified reference material (CRM) available for
      sewage sludge, the accuracy of the analytical procedure was checked by the
      analysis of CRM PACS-2 (marine sediment) and a spiked sludge sample. Good
      agreement between determined and certified values was obtained. Sewage sludge
      from a local wastewater treatment plant was analysed and the results compared
      with data from the literature.

PMID- 18346750
TI  - Self-assembly of cetylpyridinium chloride in water-DMF binary mixtures: a
      spectroscopic and physicochemical approach.
AB  - The aggregation behavior of cetylpyridinium chloride (CPyCl) in N,N
      dimethylformamide (DMF)-water mixed solvents was investigated using electrical
      conductivity and spectroscopic techniques. Micellar and thermodynamic parameters
      (DeltaG(m)(0), DeltaH(m)(0), DeltaS(m)(0) and Delta(m)C(p)(0)) were obtained from
      the temperature dependence of critical micelle concentrations in various aqueous
      mixtures of DMF. The differences in the Gibbs energies of micellization of CPyCl
      between water and binary solvents were determined to evaluate the influence of
      the cosolvent. The effect of cosolvent on the Krafft temperature (K(T)) and on
      the aggregation number was also analyzed. Micellar micropolarity was examined
      spectrophotometrically using two different probes, methyl orange (MO) and
      methylene blue (MB), and was found to increase with DMF addition, accompanied by
      an enhanced solvation. The mechanism of docking of surfactant and the probe
      molecules in the system were obtained by using Fourier transform infrared
      spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy.

PMID- 18346751
TI  - Interaction of DNA bases with silver nanoparticles: assembly quantified through
      SPRS and SERS.
AB  - Colloidal silver nanoparticles were prepared by reducing silver nitrate with
      sodium borohydride. The synthesized silver particles show an intense surface
      plasmon band in the visible region. The work reported here describes the
      interaction between nanoscale silver particles and various DNA bases (adenine,
      guanine, cytosine, and thymine), which are used as molecular linkers because of
      their biological significance. In colloidal solutions, the color of silver
      nanoparticles may range from red to purple to orange to blue, depending on the
      degree of aggregation as well as the orientation of the individual particles
      within the aggregates. Transmission electron microscopy (TEM), X-ray diffraction
      (XRD), and absorption spectroscopy were used to characterize the assemblies. DNA
      base-induced differential silver nanoparticle aggregation was quantified from the
      peak separation (relates to color) of surface plasmon resonance spectroscopy
      (SPRS) and the signal intensity of surface-enhanced Raman scattering (SERS),
      which rationalize the extent of silver-nucleobase interactions.

PMID- 18346752
TI  - Arsenic sorption onto laterite iron concretions: temperature effect.
AB  - We investigated arsenate and arsenite sorption onto laterite iron concretions
      (LIC) to test its suitability for use in the low-tech treatment of arsenic
      bearing drinking water. Batch experiments on crushed LIC from Prestea, Ghana were
      conducted at a series of temperatures, ionic strengths, and pHs. The point of
      zero net charge on laterite iron concretion was determined by potentiometric
      titrations yielding an average pHp(ZNC) around 8.64. Experiments show that
      sorption capacity for both arsenite and arsenate increase with temperature. The
      equilibrium sorption capacity for arsenite was larger than that for arsenate over
      the 25 to 60 degrees C temperature range. A Langmuir model satisfactorily fits
      the arsenite and arsenate sorption isotherm data. Both arsenite and arsenate
      sorbed over the pH range of natural waters. Arsenite sorption increases with
      increasing solution pH to a maximum at pH 7, then decreases with further increase
      in solution pH. Arsenate sorption, on the other hand, shows little change with
      increasing solution pH. Increasing solution ionic strength 10-fold results in a
      slight increase in sorption. Ionic strength experiments show that an inner-sphere
      sorption mechanism is responsible for As (V) sorption on LIC, while As (III)
      sorption is by an outer-sphere mechanism. Gibbs free energy (DeltaG degrees) for
      arsenite and arsenate sorption onto LIC was calculated from Langmuir isotherms;
      the negative values agree with reaction spontaneity. The positive values of the
      standard enthalpy (DeltaH degrees) show the endothermic nature of arsenite and
      arsenate sorption onto LIC. Positive entropy (DeltaS degrees) values suggest the
      affinity of LIC for the arsenic species in solution. Analysis of the arsenic
      sorption data suggests that LIC can be used for low-tech natural-materials
      arsenic water treatment. Laterite iron concretions have a number of advantages
      for this use over commercial materials, including the ability to remove arsenic
      from waters with a wide range in pH, the ability to sorb both common arsenic
      aqueous species equally well, and cost less. Laterite iron concretion's positive
      sorption temperature dependence will enhance sorption in tropical climates, and
      more especially in areas where groundwater sources are related to geothermal
      springs.

PMID- 18346753
TI  - Physicochemical and catalytic properties of grafted vanadium species on different
      mesoporous silicas.
AB  - Vanadium modified mesoporous silicas type MCM-41, MCM-48, and SBA-15 are obtained
      by a solid state method. The samples are characterized and compared at the
      different steps of their preparation by X-ray diffraction, N(2)-physisorption,
      FTIR, UV-vis, XPS, and TG-TPR. Samples catalytic activity is tested in
      ethylacetate oxidation. Formation of various vanadium species, mainly isolated
      and small oligomeric ones, grafted to the support surface silanol groups, is
      observed. It is found that the state and the properties of the vanadium species
      depend on the porous characteristics of the silica host matrix. The nature of the
      catalytic active center in the ethylacetate oxidation is discussed.

PMID- 18346754
TI  - Efficient recovery of a functional extracellular domain of bovine IgG2 Fc
      receptor (boFcgamma2R) from inclusion bodies by a rapid dilution refolding
      system.
AB  - The extracellular domain of the boFcgamma2R gene was constructed and cloned into
      the Escherichia coli expression vector pET-28a. The recombinant protein was
      expressed at high level in E. coli BL21(DE3) and existed mainly as inclusion
      bodies. The inclusion bodies were solubilized in 6 M guanidine hydrochloride and
      refolded by rapid dilution. After renaturation, the purity of the recovered
      recombinant protein was up to 95%. ELISA assay showed that the renatured
      recombinant protein could inhibit bovine IgG2 binding to expressed boFcgamma2R on
      the COS-7 cell surface with an IC50 value of 0.68 microM. The overall yield of
      the active rsbo2R was up to 20 mg/l of culture. Crystals of the rsbo2R were grown
      at 293 K by the hanging-drop vapour diffusion method showed weak diffraction.

PMID- 18346755
TI  - Multi-year survival of sugarbeet root maggot (Tetanops myopaeformis) larvae in
      cold storage.
AB  - To test the hypothesis that long-term survival of sugarbeet root maggot in
      storage is facilitated by larvae undergoing prolonged diapause, respiration and
      gene expression patterns of field-collected diapausing larvae were compared with
      those of 1-, 2-, and 5-year laboratory-stored larvae. Additional assessments were
      made on post-storage survival, emergence, and reproductive fitness of stored
      larvae. Respirometry, carried out at 5 and 20 degrees C revealed no differences
      among respiration rates of initially diapausing and long-term stored larvae. A 15
      degrees increase in temperature elevated respiration in both diapausing and
      stored larvae, with levels of CO2 release ranging between 8- and 14-fold higher
      at 20 degrees C than at 5 degrees C. Similarly, 6-10-fold increases in O2
      consumption levels were observed at the higher temperature. A transcript with
      sequence similarity to the fat body protein 2 (Fbp2) gene was highly expressed in
      diapausing larvae, and trace levels were expressed in some samples of 1-year
      stored larvae. However, no expression was detected in 2- and 5-year stored
      larvae. Survival and emergence studies of stored larvae revealed mixed
      populations of diapausing (i.e., the 5-17% of larvae that did not pupate) and
      post-diapausing (62-84% of larvae pupated) insects, with a high incidence of
      pupation (62%) and emergence (47%), even after 4 years in cold storage.
      Therefore, extended survival of Tetanops myopaeformis larvae in long-term cold
      storage is facilitated by two mechanisms, with a majority of larvae in post
      diapause quiescence and a smaller fraction in a state of prolonged diapause.

PMID- 18346756
TI  - Pathogenic effect of entomopathogenic nematode-bacterium complexes on terrestrial
      isopods.
AB  - In this study, we evaluated the effect of entomopathogenic nematodes (EPNs)
      Steinernema carpocapsae, Steinernema feltiae and Heterorhabditis bacteriophora,
      symbiotically associated with bacteria of the genera Xenorhabdus or Photorhabdus,
      on the survival of eight terrestrial isopod species. The EPN species S.
      carpocapsae and H. bacteriophora reduced the survival of six isopod species while
      S. feltiae reduced survival for two species. Two terrestrial isopod species
      tested (Armadillidium vulgare and Armadillo officinalis) were found not to be
      affected by treatment with EPNs while the six other isopod species showed
      survival reduction with at least one EPN species. By using aposymbiotic S.
      carpocapsae (i.e. without Xenorhabdus symbionts), we showed that nematodes can be
      isopod pathogens on their own. Nevertheless, symbiotic nematodes were more
      pathogenic for isopods than aposymbiotic ones showing that bacteria acted
      synergistically with their nematodes to kill isopods. By direct injection of
      entomopathogenic bacteria into isopod hemolymph, we showed that bacteria had a
      pathogenic effect on terrestrial isopods even if they appeared unable to multiply
      within isopod hemolymphs. A developmental study of EPNs in isopods showed that
      two of them (S. carpocapsae and H. bacteriophora) were able to develop while S.
      feltiae could not. No EPN species were able to produce offspring emerging from
      isopods. We conclude that EPN and their bacteria can be pathogens for terrestrial
      isopods but that such hosts represent a reproductive dead-end for them. Thus,
      terrestrial isopods appear not to be alternative hosts for EPN populations
      maintained in the absence of insects.

PMID- 18346757
TI  - Delirium in two patients with Bickerstaff's brainstem encephalitis.
AB  - In this report, we describe the case of two patients with Bickerstaff's brainstem
      encephalitis (BBE) who developed delirium manifested as emotional incontinence,
      restlessness, and aggressive behavior from disease onset. Serum anti-GQ1b and
      anti-GT1a IgG antibodies were detected in both patients. When unusual psychiatric
      symptoms are observed, in addition to acute ophthalmoplegia and ataxia,
      neurologists should take into account the possibility of BBE. Brain MRI findings
      were normal in both patients and SPECT was performed on only patient 1. SPECT of
      patient 1 showed reversible hypoperfusion in the brainstem, bilateral thalami,
      and medial frontal lobe. Brain SPECT appears to be useful for detecting lesions
      of the brainstem as well as the basal ganglia or cerebrum in BBE.

PMID- 18346758
TI  - Relaxing the zero-sum assumption in neutral biodiversity theory.
AB  - The zero-sum assumption is one of the ingredients of the standard neutral model
      of biodiversity by Hubbell. It states that the community is saturated all the
      time, which in this model means that the total number of individuals in the
      community is constant over time, and therefore introduces a coupling between
      species abundances. It was shown recently that a neutral model with independent
      species, and thus without any coupling between species abundances, has the same
      sampling formula (given a fixed number of individuals in the sample) as the
      standard model [Etienne, R.S., Alonso, D., McKane, A.J., 2007. The zero-sum
      assumption in neutral biodiversity theory. J. Theor. Biol. 248, 522-536]. The
      equilibria of both models are therefore equivalent from a practical point of
      view. Here we show that this equivalence can be extended to a class of neutral
      models with density-dependence on the community-level. This result can be
      interpreted as robustness of the model, i.e. insensitivity of the model to the
      precise interaction of the species in a neutral community. It can also be
      interpreted as a lack of resolution, as different mechanisms of interactions
      between neutral species cannot be distinguished using only a single snapshot of
      species abundance data.

PMID- 18346759
TI  - PPARalpha activators upregulate eNOS activity and inhibit cytokine-induced NF
      kappaB activation through AMP-activated protein kinase activation.
AB  - Endothelium-derived NO is an important mediator of vascular protection and
      adhesion molecule expression on the endothelial cell surface is critical for
      leukocyte recruitment to atherosclerotic lesions. We hypothesized that AMP
      activated protein kinase (AMPK) activity is a down-stream mediator of the
      beneficial effects of PPARalpha activators on vascular endothelial cells.
      Treatment of human umbilical vein endothelial cells (HUVEC) with fenofibrate or
      WY14643 resulted in transient activation of AMPK, as monitored by phosphorylation
      of AMPK and its down-stream target, acetyl-CoA carboxylase. Fenofibrate caused
      phosphorylation of Akt and eNOS, leading to increased production of NO, and also
      caused inhibition of cytokine-induced NF-kappaB activation, leading to
      suppression of expression of adhesion molecule genes. Significant decreases in
      eNOS activity and NO production in response to fenofibrate were observed in cells
      treated with AMPK siRNA or with AraA, a pharmacological inhibitor of AMPK. The
      attenuation of fenofibrate-induced inhibition of NF-kappaB activation was
      observed in mouse endothelial (SVEC4) cells treated with AMPK siRNA or with AraA.
      We demonstrated that TNFalpha stimulates IkappaB-alpha phosphorylation through
      induction of IKK activity, and that fenofibrate inhibits IKK activity and
      TNFalpha-induced IkappaB-alpha phosphorylation. Our findings suggest that the
      beneficial effects of PPARalpha activators on endothelial cells such as
      inhibition of diabetic microangiopathy might be attributed to the induction of
      AMPK activation beyond its lipid-lowering actions.

PMID- 18346760
TI  - Stability and Hopf bifurcation for a prey-predator model with prey-stage
      structure and diffusion.
AB  - In this paper, we first propose a prey-predator model with prey-stage structure
      and diffusion. Then we discuss the following three problems: (1) stability of non
      negative constant steady states for the reduced ODE system and the corresponding
      reaction diffusion system with homogeneous Neumann boundary conditions; (2) Hopf
      bifurcation for the ODE system; (3) Hopf bifurcation created by diffusion.

PMID- 18346761
TI  - A comparison of two predator-prey models with Holling's type I functional
      response.
AB  - In this paper, we analyze a laissez-faire predator-prey model and a Leslie-type
      predator-prey model with type I functional responses. We study the stability of
      the equilibrium where the predator and prey coexist by both performing a
      linearized stability analysis and by constructing a Lyapunov function. For the
      Leslie-type model, we use a generalized Jacobian to determine how eigenvalues
      jump at the corner of the functional response. We show, numerically, that our two
      models can both possess two limit cycles that surround a stable equilibrium and
      that these cycles arise through global cyclic-fold bifurcations. The Leslie-type
      model may also exhibit super-critical and discontinuous Hopf bifurcations. We
      then present and analyze a new functional response, built around the arctangent,
      that smoothes the sharp corner in a type I functional response. For this new
      functional response, both models undergo Hopf, cyclic-fold, and Bautin
      bifurcations. We use our analyses to characterize predator-prey systems that may
      exhibit bistability.

PMID- 18346762
TI  - Anticonvulsant characteristics of pyridoxyl-gamma-aminobutyrate, PL-GABA.
AB  - GABA is the major inhibitory neurotransmitter in the central nervous system, and
      its concentration in the brain in associated with a variety of neurological
      disorders, including seizures, convulsions, and epilepsy. The concentration of
      GABA is modulated by the pyridoxal-5'-phosphate (PLP)-dependent enzymes, GAD and
      GABA-T. In this study, we generated pyridoxyl-gamma-aminobutyrate (PL-GABA), a
      novel GABA analogue composed of pyridoxyl and GABA, and have also characterized
      its anticonvulsant and pharmacological functions in vitro. The results of
      biodistribution studies revealed that PL-GABA is capable of crossing the blood
      brain barrier. PL-GABA evidenced anticonvulsant activity in a wide range of
      epilepsy models, some of which were electrically-based (MES seizures) and some
      chemically-based (bicuculline, pentylenetetrazol (PTZ), picrotoxine, 3
      mercaptopropionic acid). Following a timed subcutaneous administration of PTZ to
      mice, PL-GABA consistently increased the latencies to first twitch and clonus. In
      addition, PL-GABA displayed no signs of tolerance after subchronic (10 day)
      treatment. PL-GABA appears to exert its anticonvulsant effects by influencing
      seizure spread and by raising the seizure threshold. Therefore, our results
      indicate that PL-GABA exerts a broad-spectrum anticonvulsant effect, and identify
      the potential for reduced PL-GABA tolerance as an additional positive profile for
      novel antiepileptic drugs.

PMID- 18346763
TI  - Regional homogeneity, functional connectivity and imaging markers of Alzheimer's
      disease: a review of resting-state fMRI studies.
AB  - Resting-state functional magnetic resonance imaging (fMRI), a promising technique
      for measuring brain activities during rest, has attracted much attention in the
      past few years. In this paper, we review recent progress on the study of
      Alzheimer's disease (AD) based on resting-state fMRI. First, we briefly introduce
      some AD-related studies from other groups. Then we describe our AD-related work
      in detail from three aspects: (1) alterations in regional homogeneity (ReHo) of
      the fMRI signal in the resting state, (2) altered patterns of functional
      connectivity from regions of interest and whole brain analyses, and (3)
      discriminative analyses based on classification features from resting-state fMRI
      data for differentiating AD patients from healthy elders. Finally, we summarize
      the main results and some prospects for future work.

PMID- 18346764
TI  - Altered deactivation in individuals with genetic risk for Alzheimer's disease.
AB  - Regions that show task-induced deactivations may be part of a default-mode
      network related to processes that are more engaged during passive than active
      task conditions. Alteration of task-induced deactivations with age and dementia
      is indicated by atypical engagement of default-mode network regions. Genetic
      studies show a relation between the apolipoprotein E4 (APOE4) allele and the
      common form of Alzheimer's disease (AD), and altered functional brain activation
      has been observed in non-demented APOE4 carriers compared to non-carriers. Here
      we investigate the hypothesis of altered default-mode network brain responses in
      individuals with genetic risk for AD. Functional MRI was used to assess task
      induced deactivation in 60 subjects of which 30 carried at least one copy of the
      APOE4 allele, and 30 non-carriers. Subjects were scanned while performing a
      semantic categorization task shown to promote episodic memory encoding. The
      results show patterns of deactivation consistent with the default-mode network.
      We also found reduced deactivation in non-demented APOE4 carriers compared to non
      carriers, suggesting alterations in the default-mode network in the absence of
      dementia. These results implicate possibilities for investigating altered
      properties of task-induced deactivations in individuals with genetic risk for AD,
      and may prove useful for pre-clinical identification of individuals susceptible
      to memory problems and AD.

PMID- 18346765
TI  - Temporary inactivation of the supramammillary area impairs spatial working memory
      and spatial reference memory retrieval.
AB  - The aim of our study was to examine the supramammillary (SuM) area involvement in
      spatial memory. Sprague-Dawley rats with chronically implanted cannula in the
      supramammillary area were trained in two spatial memory tasks with different
      memory demands: reference and working memory. In the spatial reference memory
      task, the rats received microinjections in the SuM area of tetrodotoxin (TTX)
      (0.5 ng diluted in 0.5 microL of saline) or saline (0.5 microL). The
      microinjections were administered 30 min before the spatial training (day 4) (to
      assess the effect on acquisition) and on the following two days (days 5 and 6)
      the training was conducted without microinjections (to study the effect on
      consolidation). On the last training day (day 7), in order to assess the
      retrieval of spatial information, the rats received the microinjections 30 min
      before the spatial training. The spatial working memory used was a delayed
      matching-to-position (DMTP) task. Spatial training was performed for seven days.
      During the first three days of the spatial training, the rats achieved a good
      spatial knowledge and learnt the working memory rule necessary to solve the
      spatial task. On days 4 and 6, the rats received microinjections to study
      involvement of the SuM area in working memory. The results showed that temporary
      inactivation of SuM area impairs both the rat's ability to solve a spatial
      working memory task with DMTP demands and the recovery of spatial information in
      a spatial reference memory task. We suggest that SuM area is involved in the
      rearrangement of spatial information during spatial working memory tasks with
      DMTP memory demands.

PMID- 18346766
TI  - Effects of rat odour and shelter on maternal behaviour in C57BL/6 dams and on
      fear and stress responses in their adult offspring.
AB  - Recent studies in rats and mice suggest that developmental plasticity of HPA
      stress and fear responses could be mediated by environment-dependent variations
      in maternal behaviour. The present study was designed to examine this question
      further by varying the adversity of the maternal environment to study its effects
      on nest-attendance and maternal care and on the HPA and fear responses in the
      adult offspring. C57BL/6 dams and their litter were housed in a cage system
      composed of a nest cage (NC) and a foraging cage (FC) connected by a tunnel.
      Using a 2 x 2 factorial design, we varied the maternal foraging environment (FC)
      by the presence or absence of rat odour (feces) and shelters (MouseHouse and
      tube) from postnatal days 1-14 and assessed the adult offspring's corticosterone
      response to isolation/novelty stress and their behaviour in three tests of
      fearfulness (elevated-O-maze, open-field, free exploration). While the presence
      of shelters in the FC reduced time spent in the NC (nest site attendance), the
      presence of rat odour in the FC increased active maternal care without altering
      nest site attendance. Alterations of the offspring's HPA and fear responses were
      rather subtle. The presence of shelters in the dam's foraging environment
      decreased fearfulness in the offspring in the free exploration test. In addition,
      males reared by dams exposed to rat odour were less fearful in the open-field
      test, and both males and females reared by dams without shelters and rat odour in
      the FC showed a greater corticosterone response to isolation/novelty stress.
      Multiple regression analysis indicated a negative relationship between maternal
      licking/grooming and fearfulness in males and a positive relationship between
      nest site attendance and fearfulness in females. Taken together, these results
      indicate that mouse dams adjust specific aspects of maternal behaviour in
      response to the specific properties of their environment, and that active
      maternal care and nest site attendance are two aspects of maternal behaviour that
      may affect the offspring's stress and fear systems independent of each other and
      in a sex-specific way.

PMID- 18346767
TI  - Contributions of conserved serine and tyrosine residues to catalysis, ligand
      binding, and cofactor processing in the active site of tyrosine ammonia lyase.
AB  - Tyrosine ammonia lyase (TAL) catalyzes the conversion of L-tyrosine to p-coumaric
      acid using a 3,5-dihydro-5-methylidene-4H-imidazole-4-one (MIO) prosthetic group.
      In bacteria, TAL is used for production of the photoactive yellow protein
      chromophore and for caffeic acid biosynthesis in certain actinomycetes. Here we
      biochemically examine wild-type and mutant forms of TAL from Rhodobacter
      sphaeroides (RsTAL). Kinetic analysis of RsTAL shows that the enzyme displays a
      90-fold preference for L-tyrosine versus L-phenylalanine as a substrate. The pH
      dependence of TAL activity with L-tyrosine and L-phenylalanine demonstrates a
      common protonation state for catalysis, but indicates a difference in charge
      state for binding of either amino acid. Site-directed mutagenesis demonstrates
      that Ser150, Tyr60, and Tyr300 are essential for catalysis. Mutation of Ser150 to
      an alanine abrogates formation of the MIO prosthetic group, as shown by mass
      spectrometry, and prevents catalysis. The Y60F and Y300F mutants were inactive
      with both amino acid substrates, but bound p-coumaric and cinnamic acids with
      less than 12-fold changes in affinity compared the wild-type enzyme. Analysis of
      MIO-dithiothreitol adduct formation shows that the reactivity of the prosthetic
      group is not significantly altered by mutation of either Tyr60 or Tyr300. The
      mechanistic roles of Ser150, Tyr60, and Tyr300 are discussed in relation to the
      three-dimensional structure of RsTAL and related MIO-containing enzymes.

PMID- 18346768
TI  - Evaluation the Clinitek status automated dipstick analysis device for
      semiquantitative testing of canine urine.
AB  - The aim of this prospective study was to evaluate the Clinitek status analyser
      using Multistix10SG/Microalbustix dipsticks (all: Siemens Dx) for canine urine
      (n=101) compared to reference methods: visual reading (Combur9 dipstick, Roche),
      refractometry, microscopy, and quantitative protein/creatinine analysis
      (Pentra400, AxonLab). The automated analyses were done twice and visual tests
      were performed by two examiners. An excellent to good concordance was
      demonstrated between the first/second analysis with the Multistix10SG and the
      Combur9 dipstick, respectively with Cohen's kappa-values ranging from 0.776 to
      1.000. Agreement between both dipsticks was good for glucose (kappa=0.753), blood
      (kappa=0.793), protein (kappa=0.788), and moderate for bilirubin (kappa=0.431)
      and ketones (kappa=0.540). In 6/101 specimens, false positive ketone reactions
      were obtained with the Multistix10SG. Multistix10SG could not be used for
      determination of pyuria or specific gravity. Semiquantitative/quantitative
      protein results correlated well (rho=0.90) and creatinine measurements moderately
      (rho=0.76). Due to automated data transmission to the laboratory information
      system, the Clinitek status is of advantage in veterinary laboratories/clinics.

PMID- 18346769
TI  - Issues in defining and measuring facial cleanliness for national trachoma control
      programs.
AB  - The WHO trachoma control strategy includes promotion of facial cleanliness to
      interrupt transmission. However, scant data exist on measuring a clean face. Our
      goals were to determine reliable indicators of a clean face in a child, and
      disparities between the assessments of faces at a clinic versus at home. Five
      hallmarks of a clean face were assessed on 50 children in Tanzania. In five
      districts, 973 children (age 1-5 years) were evaluated for facial cleanliness at
      home, and again 2 days later at a central location for a trachoma examination.
      Data on environmental risk factors were collected. Only three signs, ocular and
      nasal discharge, and flies on the face, were reliable indicators of facial
      cleanliness (kappa>0.6); dust and food were less reliable. Unclean faces were
      more prevalent when measured at home (62%) than at the clinic (51%), although
      both were related to trachoma. The environmental markers of absence of latrines
      and tin roofs were consistent markers across all districts of households at risk
      of poor facial cleanliness. We conclude that for accurate estimates of clean
      faces, some assessment strategy outside the clinical environment is necessary.
      Additionally, behavior change programs in these districts in Tanzania should
      especially target families without tin roofs or latrines.

PMID- 18346770
TI  - Treatment of human fascioliasis with triclabendazole: good news.

PMID- 18346771
TI  - Microarray analysis in rat liver slices correctly predicts in vivo
      hepatotoxicity.
AB  - The microarray technology, developed for the simultaneous analysis of a large
      number of genes, may be useful for the detection of toxicity in an early stage of
      the development of new drugs. The effect of different hepatotoxins was analyzed
      at the gene expression level in the rat liver both in vivo and in vitro. As in
      vitro model system the precision-cut liver slice model was used, in which all
      liver cell types are present in their natural architecture. This is important
      since drug-induced toxicity often is a multi-cellular process involving not only
      hepatocytes but also other cell types such as Kupffer and stellate cells. As
      model toxic compounds lipopolysaccharide (LPS, inducing inflammation),
      paracetamol (necrosis), carbon tetrachloride (CCl(4), fibrosis and necrosis) and
      gliotoxin (apoptosis) were used. The aim of this study was to validate the rat
      liver slice system as in vitro model system for drug-induced toxicity studies.
      The results of the microarray studies show that the in vitro profiles of gene
      expression cluster per compound and incubation time, and when analyzed in a
      commercial gene expression database, can predict the toxicity and pathology
      observed in vivo. Each toxic compound induces a specific pattern of gene
      expression changes. In addition, some common genes were up- or down-regulated
      with all toxic compounds. These data show that the rat liver slice system can be
      an appropriate tool for the prediction of multi-cellular liver toxicity. The same
      experiments and analyses are currently performed for the prediction of human
      specific toxicity using human liver slices.

PMID- 18346772
TI  - A hyaluronidase from Potamotrygon motoro (freshwater stingrays) venom: isolation
      and characterization.
AB  - Freshwater stingrays (Potamotrygon motoro) are known to cause human accidents
      through a sting located in its tail. In the State of Goias, this accident happens
      especially during the fishing season of the Araguaia River. The P. motoro venom
      extracted from the sting presented hyaluronidase activity. The enzyme was
      purified by gel filtration on Sephacryl S-100 and ion-exchange chromatography on
      SP-Sepharose. A typical procedure provided 376.4-fold purification with a 2.94%
      yield. The molecular weight of the purified enzyme was 79 kDa as estimated by gel
      filtration on Sephacryl S-100. The K(m) and V(max) values for hyaluronidase,
      using hyaluronic acid as substrate, were 4.91 microg/ml and 2.02 U/min,
      respectively. The pH optimum for the enzyme was pH 4.2 and maximum activity was
      obtained at 40 degrees C. The hyaluronidase from P. motoro was shown to be heat
      instable, being stabilized by bovine albumin and DTT, and inhibited by Fe(2+),
      Mn(2+), Cu(2+) and heparin.

PMID- 18346773
TI  - Intersexual variations in Northern (Missulena pruinosa) and Eastern (M. bradleyi)
      mouse spider venom.
AB  - Venoms of both sexes of Australian Northern (Missulena pruinosa) and Eastern
      (Missulena bradleyi) mouse spiders were studied in order to determine intersexual
      variations in venom yield, composition and bioactivity. Females of both species
      yielded more venom than males. High-performance liquid chromatography (HPLC) and
      mass spectrometry data further indicate a substantial degree of intersexual
      variation in the venom composition of both species. In a cricket (Acheta
      domestica) acute toxicity assay, only small intersexual differences were
      observed, but M. bradleyi venom was found to be considerably more potent than M.
      pruinosa venom. In the chick biventer cervicis nerve-muscle preparation, male but
      not female M. bradleyi venom induced large and sustained muscle contractions with
      fasciculation and decreased twitch height that could be reversed by CSL funnel
      web spider antivenom. In contrast, venoms of both sexes of M. pruinosa did not
      induce significant effects in the chick biventer cervicis nerve-muscle
      preparation. We therefore conclude that female M. bradleyi venom and venoms from
      male and female M. pruinosa appear to contain few, if any, orthologs of delta
      missulenatoxin-Mb1a, the toxin responsible for the effects of male M. bradleyi
      venom in vertebrates. These findings are consistent with clinical reports that
      mouse spiders, particularly species other than male M. bradleyi, do not appear to
      be a major medical problem in humans.

PMID- 18346774
TI  - Necessary but not sufficient: motion perception is required for perceiving
      biological motion.
AB  - Researchers have argued that biological motion perception from point-light
      animations is resolved from stationary form information. To determine whether
      motion is required for biological motion perception, we measured discrimination
      thresholds at isoluminance. Whereas simple direction discriminations falter at
      isoluminance, biological motion perception fails entirely. However, when
      performance is measured as a function of contrast, it is apparent that biological
      motion is contrast-dependent, while direction discriminations are contrast
      invariant. Our results are evidence that biological motion perception requires
      intact motion perception, but is also mediated by a secondary mechanism that may
      be the integration of form and motion, or the computation of higher-order motion
      cues.

PMID- 18346775
TI  - Biometric measurement of the mouse eye using optical coherence tomography with
      focal plane advancement.
AB  - PURPOSE: To demonstrate that high-resolution biometry is possible in mouse eyes
      in vivo, using real-time OCT with focal plane advancement by a stepper motor.
      METHODS: OCT images of eyes were taken from nine 29-day-old C57BL/6 mice(18 eyes)
      on two consecutive days. A custom-built real-time OCT instrument with a stepper
      motor was used to advance the focal plane from the corneal apex to the retina
      along the ocular axis. The ocular dimensions were determined by advancement of
      the stepper motor as it displayed on the OCT scan images. RESULTS: OCT images of
      the entire eye, including the cornea, anterior chamber, lens, vitreous chamber,
      and retina, were successfully obtained from both eyes of all mice. The measured
      average corneal thickness from 18 eyes at the age of 29 days was 90.8+/
      4.6microm, anterior chamber depth 707.4+/-21.4microm, lens thickness 1558.7+/
      18.0microm, vitreous chamber depth 707.4+/-21.4microm and retinal thickness was
      186.9+/-15.1microm. Total axial length (from the corneal apex to the nerve fiber
      layer of the retina) was 3003.3+/-44.1microm. None of them were significantly
      different if measured on two consecutive days, and no significant differences
      were found between measurements in the left and right eyes. CONCLUSION: By focal
      plane advancement of a real-time OCT instrument through the mouse eye, highly
      repeatable measurements of the ocular dimensions were obtained. This novel method
      may be used to study small animal models of normal and abnormal eye development.

PMID- 18346776
TI  - In vitro assessment of the effects of cadmium and zinc on mammalian nerve fibres.
AB  - Zinc and cadmium are environmental contaminants that have a wide range of effects
      on the nervous system, but zinc is also considered to be an important metal in
      the human body. In this study the effect of CdCl(2) and ZnCl(2), at
      concentrations of 50,150, 250 and 500 microM, on the nerve fibres of the sciatic
      nerve of the rat isolated in a three-chamber recording bath were studied. At the
      same concentrations, CdCl(2) and ZnCl(2) were found to have almost the same
      inhibitory effect on the compound action potential (CAP) of the nerve fibres.
      Their concentration-effect curves almost overlap and there was no significant
      difference in their EC(50) which for CdCl(2) is 250.1+/-18 microM (n=5) and for
      ZnCl(2) is 282.2+/-25 microM (n=5) correspondingly (P>0.05). The no-observed
      effect concentration (NOEC) was estimated to be 50-100 microM for both metals.
      The identical inhibitory effect of both metals on the sciatic nerve fibres
      indicates a common mode of action which is related to their potential to generate
      reactive oxygen species (ROS).

PMID- 18346778
TI  - Cell type specificity of lung cancer associated with air pollution.
AB  - The aim of this study is to explore whether lung cancer associated with air
      pollution has cell type specificity. The air quality data (SO(2), CO, O(3), NOx)
      from the Taiwan EPA's air quality monitoring stations were collected between 1995
      and 1998. Patients with lung cancer were identified through the National Cancer
      Registration Program operated by the Taiwanese government. Two major pathological
      types (adenocarcinoma (AC) and squamous cell carcinoma (SCC)) were considered.
      The Pearson correlation coefficients between the air quality index and age
      standardized incidence rate per 100,000 person years (ASR) of AC and SCC were
      calculated for both genders for three township categories characterized by
      different levels of air pollution. The traffic-related NOx and CO showed
      significant correlations with female lung cancer incidence rate, with Pearson's
      correlation 0.33 (P=0.03) and 0.40 (P=0.01) respectively. However, the
      correlation between air pollution and lung cancer was not significant for males.
      Significant correlation coefficients were also found between the ratio of AC/SCC
      and the mean concentrations of NOx (r=0.41, P=0.04) and CO (r=0.47, P=0.02) in
      females. Our results show that the worse the air pollution was in the area, the
      higher the AC rate, regardless of gender. On the other hand, SCC incidence rates
      did not increase with increasing air pollution. Our results show that a
      correlation exists between air pollution and lung adenocarcinoma incidence.

PMID- 18346777
TI  - DNA double-strand breaks: a potential causative factor for mammalian aging?
AB  - Aging is a pleiotropic and stochastic process influenced by both genetics and
      environment. As a result the fundamental underlying causes of aging are
      controversial and likely diverse. Genome maintenance and in particular the repair
      of DNA damage is critical to ensure longevity needed for reproduction and as a
      consequence imperfections or defects in maintaining the genome may contribute to
      aging. There are many forms of DNA damage with double-strand breaks (DSBs) being
      the most toxic. Here we discuss DNA DSBs as a potential causative factor for
      aging including factors that generate DNA DSBs, pathways that repair DNA DSBs,
      consequences of faulty or failed DSB repair and how these consequences may lead
      to age-dependent decline in fitness. At the end we compare mouse models of
      premature aging that are defective for repairing either DSBs or UV light-induced
      lesions. Based on these comparisons we believe the basic mechanisms responsible
      for their aging phenotypes are fundamentally different demonstrating the complex
      and pleiotropic nature of this process.

PMID- 18346779
TI  - Acute effects of Benzo[a]pyrene, anthracene and a fuel oil on biomarkers of the
      common goby Pomatoschistus microps (Teleostei, Gobiidae).
AB  - The objective of this study was to investigate the effects of two different PAHs
      and a complex petrochemical mixture on the common goby, Pomatoschistus microps,
      using selected biomarkers as effect criteria. Benzo[a]pyrene (BaP) and anthracene
      were used as reference substances, while the water accommodated fraction of #4
      fuel-oil (#4 WAF) was used as an example of a petrochemical mixture. P. microps
      was used since it is both a suitable bioindicator and a good test organism.
      Groups of fish were exposed to different concentrations of each of the test
      substances for 96 h and the activities of several enzymes commonly used as
      biomarkers were determined at the end of the bioassays. All the substances
      inhibited P. microps acetylcholinesterase (AChE) indicating that they have at
      least one mechanism of neurotoxicity in common: the disruption of cholinergic
      transmission by inhibition of AChE. An induction of lactate dehydrogenase (LDH)
      activity was found in fish exposed to BaP or to anthracene, suggesting an
      increase of the anaerobic pathway of energy production. On the contrary,
      inhibition of LDH was found in fish exposed to #4 WAF, suggesting a distinct
      effect of the mixture. An induction of P. microps glutathione S-transferase (GST)
      activity was found in fish exposed to BaP or to #4 WAF, while an inhibition was
      observed after exposure to anthracene. These results suggest that GST is involved
      in the detoxification of BaP and #4 WAF, but not of anthracene. All the
      substances increased catalase activity and isolated PAHs also increased
      superoxide dismutase, glutathione reductase and glutathione peroxidase
      activities, while #4 WAF did not cause significant alterations on these enzymes.
      These results suggest that all the substances may induce oxidative stress on P.
      microps, with BaP and anthracene apparently having more oxidative stress
      potential than #4 WAF.

PMID- 18346780
TI  - Effect of prostaglandin F2alpha at the time of AI on progesterone levels and
      pregnancy rate in synchronized Italian Mediterranean buffaloes.
AB  - The aims of this study were to evaluate the effects of an intravenous or
      intramuscular PGF2alpha analogue administration on the day of estrus on
      progesterone concentration and pregnancy rate in buffaloes undergoing artificial
      insemination (AI). To this end, two experiments were carried out. The first study
      was performed on 72 Mediterranean buffaloes synchronized by the Ovsynch-TAI
      Program. On the day of estrus only animals considered in heat were divided into
      four groups: Groups IVC and IMC received, respectively, an intravenous or
      intramuscular injection of cloprostenol (0.524 mg), whereas control Groups IVS
      and IMS received the same injections of saline. Milk samples were collected daily
      from each animal to assess progesterone concentration in the whey by RIA method.
      In addition on alternate days, buffaloes underwent transrectal ultrasound
      analysis. The second study was carried out on 385 buffaloes synchronized by the
      Ovsynch-TAI Program. On the day of AI, animals were divided in four groups, as
      described in experiment 1. Pregnancy rate was evaluated either on day 26 or day
      45 and embryonic mortality rate was recorded. Statistical analysis was performed
      by ANOVA and chi2 test. A higher (P<0.05) progesterone concentration was recorded
      on day 11 (Day 0=estrus day) in Groups IVC and IMC compared to Groups IVS and IMS
      (351.6+/-129.7 and 355.8+/-112.2 pg ml(-1) vs. 239.8+/-81.1 and 243.6+/-90.5 pg
      ml(-1), respectively). Furthermore, a larger CL was recorded on the same day in
      treated vs. control groups (1.25+/-0.15 and 1.27+/-0.17 cm, respectively, in
      Groups IVC and IMC vs. 1.08+/-0.14 and 1.05+/-0.13 cm in IVS and IMS). In the
      second study, a higher pregnancy rate was observed in treated (IVC+IMC) vs.
      control (IVS+IMS) groups (46.7% vs. 30.7%; P<0.01), while no differences were
      recorded between treated groups. From these data, it can be concluded that either
      intravenous or intramuscular administration of PGF2alpha at the time of AI can
      enhance progesterone levels and pregnancy rate in buffaloes.

PMID- 18346781
TI  - Changes of serum albumin affinity for aspirin induced by fatty acid.
AB  - Saturated fatty acids such as myristic acid play an important role in the
      pathogenesis of cardiovascular disorders. Using the quenching fluorescence method
      we examined the influence of myristate on the changes of transporting protein
      affinity towards aspirin-the most popular anticoagulant. Our results showed that
      the presence of the myristic acid alters the stability of the anticoagulant
      albumin complex. The ranges of [myristate]/[albumin] molar ratio at which the
      stability of drug-protein complex increases or decreases were determined. The
      differences in interaction between ligands and human or bovine serum albumins
      were identified. The competition in binding of ligands with these albumins was
      also described.

PMID- 18346782
TI  - Molecular modelling of human CYP2D6 and molecular docking of a series of
      ajmalicine- and quinidine-like inhibitors.
AB  - 3D-models were created and refined for CYP2D6 and for its complexes with
      ajmalicine and quinidine. The influence of the conformation of the enzyme active
      site on its interaction with ligands was evaluated by performing three series of
      molecular docking on selected ajmalicine- and quinidine-like inhibitors. The
      results suggested that the experimental binding values of ajmalicine- and
      quinidine-like inhibitors better fit with the energetic terms derived from their
      interaction with structures of CYP2D6 obtained by, respectively, optimizing the
      ajmalicine/CYP2D6 and the quinidine/CYP2D6 complexes, rather than exploiting the
      3D-strucure of the enzyme not subjected to a ligand-induced conformational
      change. It suggests the relevance of induced-fit phenomena in the biological
      system of interest.

PMID- 18346783
TI  - Local extracellular acidification caused by Ca2+-dependent exocytosis in PC12
      cells.
AB  - Exocytosis of acidic synaptic vesicles may produce local extracellular
      acidification, but this effect has not been measured directly and its magnitude
      may depend on the geometry and pH-buffering capacity of both the vesicles and the
      extracellular space. Here we have used SNARF dye immobilized by conjugation to
      dextran to measure the release of protons from PC12 cells. The PC12 cells were
      stimulated by exposure to depolarizing K(+)-rich solution and activation was
      verified by fluorescence measurement of intracellular Ca(2+) and the release
      kinetics of GFP-labeled vesicles. Confocal imaging of the pH-dependent
      fluorescence from the immobile extracellular SNARF dye showed transient
      acidification around the cell bodies and neurites of activated PC12 cells. The
      local acidification was abolished when extracellular solution was devoid of
      Ca(2+) or strong pH-buffering was imposed with 10mM of HEPES. We conclude that
      the release of secretory vesicles induces local rises in proton concentrations
      that are co-released from synaptic vesicles with the primary neurotransmitter,
      and propose that the co-released protons may modulate the signaling in confined
      micro-domains of synapses.

PMID- 18346784
TI  - Bcl2 mitigates Ca2+ entry and mitochondrial Ca2+ overload through downregulation
      of L-type Ca2+ channels in PC12 cells.
AB  - Altered calcium homeostasis and increased cytosolic calcium concentrations
      ([Ca2+]c) are linked to neuronal apoptosis in epilepsy and in cerebral ischemia,
      respectively. Apoptotic programmed cell death is regulated by the antiapoptotic
      Bcl2 family of proteins. Here, we investigated the role of Bcl2 on calcium (Ca2+)
      homeostasis in PC12 cells, focusing on L-type voltage-dependent calcium channels
      (VDCC). Cytosolic Ca2+ transients ([Ca2+]c) and changes of mitochondrial Ca2+
      concentrations ([Ca2+]m) were monitored using cytosolic and mitochondrially
      targeted aequorins of control PC12 cells and PC12 cells stably overexpressing
      Bcl2. We found that: (i) the [Ca2+]c and [Ca2+]m elevations elicited by K+ pulses
      were markedly depressed in Bcl2 cells, with respect to control cells; (ii) such
      depression of [Ca2+]m was not seen either in digitonin-permeabilized cells or in
      intact cells treated with ionomycin; (iii) the [Ca2+]c transient depression seen
      in Bcl2 cells was reversed by shRNA transfection, as well as by the Bcl2
      inhibitor HA14-1; (iv) the L-type Ca2+ channel agonist Bay K 8644 enhanced K(+)
      evoked [Ca2+]m peak fourfold in Bcl2, and twofold in control cells; (v) in
      current-clamped cells the depolarization evoked by K+ generated a more
      hyperpolarized voltage step in Bcl2, as compared to control cells. Taken
      together, our experiments suggest that the reduction of the [Ca2+]c and [Ca2+]m
      transients elicited by K+, in PC12 cells overexpressing Bcl2, is related to the
      reduction of Ca2+ entry through L-type Ca2+ channels. This may be due to the fact
      that Bcl2 mitigates cell depolarization, thus diminishing the recruitment of L
      type Ca2+ channels, the subsequent Ca2+ entry, and mitochondrial Ca2+ overload.

PMID- 18346785
TI  - Does T-cell depletion have a future in allogeneic stem cell transplantation?

PMID- 18346786
TI  - Influence of bovine manure on dissipation of hexazinone in soil.
AB  - The effects of bovine manure (BM) on the degradation of hexazinone and formation
      of three of its major metabolites were investigated in sandy loam soil. The
      degradation half-life of hexazinone was 29.6 days in unamended soil, while it
      decreased to 21.8 days in BM-amended soil. The major metabolites formed in
      unamended soil were [3-cyclohexyl-6-(methylamino)-1-methyl-1,3,5-triazine-2,4(1,
      3H)-dione] (metabolite A) and [3-cyclohexyl-1-methyl-1,3,5-triazine-2,4,6(1, 3,
      5H)-trione] (metabolite C), while metabolite B [3-(4-hydroxycyclohexyl)-6
      (dimethylamino)-1-methyl-1,3,5-triazine-2,4(1, 3H)-dione] was not detected over
      the entire experimental period. However, in BM-amended soil, metabolite B was
      detected at 20 and 40 days after incubation, suggesting that BM contributed to
      formation of this metabolite. N-demethylation, removal of the dimethylamino group
      with formation of a carbonyl group at the 6-position of the triazine ring
      appeared to be the principal mechanisms involved in hexazinone metabolism in
      unamended soil. However, hydroxylation at the 4-positon of the cyclohexyl group
      as well as the above two modes were the principal pathways in BM-amended soil.

PMID- 18346787
TI  - Sexually violent predator laws and the liberal state: an ominous threat to
      individual liberty.
AB  - No other country has taken the idea of the liberal state - a government that
      relies on the rule of law to limit state power and maximize individual liberty -
      as seriously as the United States. But now many states are manipulating the
      government's civil commitment authority to indefinitely confine sex offenders who
      have served their criminal sentences and are entitled to their freedom in the
      community. This new system of preventive detention masquerading as civil
      commitment poses an ominous threat to individual liberty and to the continued
      vitality of the liberal state.

PMID- 18346788
TI  - Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide.
AB  - Anti-CD20 monoclonal antibodies have been proven to be efficient in the treatment
      of certain B-cell lymphomas and autoimmune diseases. Intriguingly, these
      antibodies seem to exert diverse functions with narrow epitope specificity. This
      study is to investigate the molecular basis of the fine specificity of 2H7
      derived antibodies which are of great therapeutic potential. We show that
      chimeric 2H7 (C2H7) can mediate complement dependent cytotoxicity and antibody
      dependent cellular cytotoxicity effects on CD20 positive human Burkitt lymphoma
      cells and the Fab fragment can well recognize and bind to an epitope peptide of
      the extracellular loop of CD20. The crystal structure of C2H7 in complex with the
      CD20 epitope peptide was determined at 2.6A resolution. The bound peptide
      displays a circular conformation and the binding specificity is mainly
      contributed by the (170)ANPS(173) motif and the disulfide bond of the peptide
      which maintains the unique conformation of the peptide. Compared with the complex
      structure of another anti-CD20 monoclonal antibody Rituximab with the same
      epitope peptide which was previously determined, the major differences lie in the
      CDR loop H3 of C2H7 which stretches outward against the interface.
      Correspondingly, the pocket which accommodates the peptide becomes wider and the
      peptide moves toward loop H3 and thus is more distant from loops H1 and H2. The
      hydrogen-bonding interactions are also quite different from those observed in the
      Rituximab-epitope peptide complex, and both the hydrophilic and hydrophobic
      interactions are less intense. Our data not only reveal the molecular basis for
      the fine specificity of C2H7 to CD20, but also provide valuable information for
      further improvement of antibodies derived from 2H7.

PMID- 18346789
TI  - Molecular characterization of the porcine GBP1 and GBP2 genes.
AB  - Experimental evidence indicated that interferon-inducible guanylate-binding
      proteins (GBPs) are similar with genes in the myxovirus (Mx) resistance protein
      subfamily of the large GTPases protein family and play important roles in the
      resistance to intracellular pathogens. As more diseases exert significant
      influence on pig industry, it is anticipated that more candidate disease
      resistance genes could be found in future strategies aimed at improving genetic
      resistance to infectious diseases. In this study, we cloned cDNA sequences and
      analyzed the genomic structure of porcine GBP1 (poGBP1) and GBP2 (poGBP2). The
      two genes were mapped to SSC4q21-q23 and SSC4q24 by the SCHP panel respectively,
      further IMpRH panel analysis showed both genes were most closely linked to the
      marker SWR153. The deduced amino acid sequences of these two genes share the same
      three classical GTP-binding motifs at the amino terminus and are less conserved
      at the carboxyl termini except for a CaaX motif, compared with human and mouse
      counterparts. The reverse transcriptase-polymerase chain reaction (RT-PCR)
      revealed that poGBP1 and poGBP2 were both widely expressed in many tissues, and
      transient transfection indicated that poGBP1 and poGBP2 proteins were both
      located in cytoplasms within Pig Kidney Epithelial cells (PK15). Quantitative
      real-time PCR (Q-RT-PCR) analyses showed poGBP1 and poGBP2 had very similar
      expression patterns in PK15 cells at different time points after poly I:C
      stimulation, suggesting that ISRE (interferon-stimulated response element) plays
      a crucial role in the transcriptional regulation of these two genes. Four single
      nucleotide polymorphisms (SNPs) and three SNPs were detected in the cDNA
      sequences of poGBP1 and poGBP2, respectively. Association analyses revealed that
      the poGBP1 Eco81I and poGBP2 SspI polymorphisms both had significant associations
      (p<0.05) with red blood cell count (RBC), haemoglobin concentration (HGB) and
      hematocrit (HCT) of 17-day-old pigs.

PMID- 18346790
TI  - Identified cases of acute hepatitis C from computerized laboratory database: a
      hospital-based epidemiological and clinical study.
AB  - OBJECTIVE: Diagnosis of acute hepatitis C (AHC) relies on documented positive
      seroconversion of antibody to hepatitis C virus (anti-HCV) that is infrequently
      encountered. To clarify the epidemiology and clinical course of AHC, we tried to
      find more AHC patients from a computerized laboratory database by using a
      supplemental criterion of rising anti-HCV titer. METHODS: All the computerized
      laboratory databases of anti-HCV and alanine aminotransferase (ALT) were
      reviewed. Candidates for AHC were identified by either anti-HCV positive
      seroconversion, rise of anti-HCV titer (signal to cut-off ratio (S/CO) ratio < 40
      to > or = 40), or spontaneous HCV RNA clearance. AHC cases and their matched
      chronic hepatitis C controls were interviewed by a case-control study concerning
      risk factors. RESULTS: AHC was identified in 123 patients (68 men and 55 women;
      median age: 48.4+/-13.9 years), who had higher rates of recent surgery (p=0.037)
      and frequent injection therapy (p=0.036) compared to controls. Self-limited AHC
      was observed in 18 (19.1%, 95% confidence interval: 12.3-25.9%) of 94 AHC
      patients who had been followed for 6 months, with a higher bilirubin level (> or
      = 2 vs. < 2, p=0.007) compared to those evolved to chronic infection.
      CONCLUSIONS: Screening of a laboratory database for anti-HCV and ALT might
      uncover more AHC candidates to disclose the epidemiology and clinical course of
      AHC.

PMID- 18346791
TI  - Prevention of atrial fibrillation following cardiac surgery: basis for a novel
      therapeutic strategy based on non-hypoxic myocardial preconditioning.
AB  - Atrial fibrillation is the most common complication of cardiac surgical
      procedures performed with cardiopulmonary bypass. It contributes to increased
      hospital length of stay and treatment costs. At present, preventive strategies
      offer only suboptimal benefits, despite improvements in anesthesia, surgical
      technique, and medical therapy. The pathogenesis of postoperative atrial
      fibrillation is considered to be multifactorial. However oxidative stress is a
      major contributory factor representing the unavoidable consequences of
      ischemia/reperfusion cycle occurring in this setting. Considerable evidence
      suggests the involvement of reactive oxygen species (ROS) in the pathogenic
      mechanism of this arrhythmia. Interestingly, the deleterious consequences of high
      ROS exposure, such as inflammation, cell death (apoptosis/necrosis) or fibrosis,
      may be abrogated by a myocardial preconditioning process caused by previous
      exposure to moderate ROS concentration known to trigger survival response
      mechanisms. The latter condition may be created by n-3 PUFA supplementation that
      could give rise to an adaptive response characterized by increased expression of
      myocardial antioxidant enzymes and/or anti-apoptotic pathways. In addition, a
      further reinforcement of myocardial antioxidant defenses could be obtained
      through vitamins C and E supplementation, an intervention also known to diminish
      enzymatic ROS production. Based on this paradigm, this review presents clinical
      and experimental evidence supporting the pathophysiological and molecular basis
      for a novel therapeutic approach aimed to diminish the incidence of postoperative
      atrial fibrillation through a non-hypoxic preconditioning plus a reinforcement of
      the antioxidant defense system in the myocardial tissue.

PMID- 18346792
TI  - A method to increase the bioactivity of plasmid DNA by heat treatment.
AB  - A method to increase the bioactivity of plasmid DNA by heat treatment has been
      developed. The structure of the heat treated plasmid DNA was investigated by
      electrophoresis assay and atomic force microscope (AFM) observation.
      Electrophoresis assay showed that the heat treated DNA consisted of three
      components: the supercoiled DNA (component I), the open circular DNA (component
      II) and the heat denatured DNA component. The bioactivity of the heat treated
      plasmid DNA was investigated by both DNA condensation experiments and gene
      transfection experiment with mammal cells. DNA condensation experiments showed
      that the heat denatured DNA component owned higher sensitivity to spermidine and
      polyethylenimine (PEI) than component I and component II DNA. Gene transfection
      experiment with PEI indicated that the heat treated DNA had higher gene
      transfection efficiency than untreated DNA. Our experiment not only shows an
      effective approach to increase the bioactivity of plasmid DNA but also leads a
      way to improve the bioactivity of DNA by physically modifying their structure.

PMID- 18346793
TI  - Detecting depression in Chinese adults with mild dementia: findings with two
      versions of the Center for Epidemiologic Studies Depression Scale.
AB  - This study investigates the extent to which the diagnostic performance of the
      Center for Epidemiologic Studies Depression Scale (CES-D; both 20- and 10-item
      versions) varies with cognitive status, and whether the same threshold can be
      applied regardless of cognitive status. Three hundred and ninety-six persons aged
      60+ referred for psychiatric assessment were broken down into four groups
      depending on age (<70 and >or=70) and dementia status (mild vs. none). All were
      independently interviewed using the CES-D before their first evaluation by a
      psychiatrist. Receiver operating characteristic curves showed that both versions
      of the CES-D produced essentially identical results, regardless of age and
      dementia status. Both versions were more or less robust to the effect of mild
      dementia but were vulnerable to the effect of age itself. Furthermore, the
      optimal threshold for the 20-item version varied somewhat across the different
      age-dementia groups, and no clear-cut threshold existed in old-old persons with
      dementia. On the contrary, the same threshold of 12 can be adopted for the 10
      item version, regardless of age and dementia status. Compared with the full 20
      item scale, the 10-item version has the added advantage of an identical threshold
      across age and cognitive status.

PMID- 18346794
TI  - Association study of a (TG)n dinucleotide repeat at chromosome 15q13.3 and
      schizophrenia in the Chinese population.
AB  - Linkage studies have suggested that chromosome 15q13-q14 may harbor a
      susceptibility locus for schizophrenia. In the current study, the association
      between a (TG)n dinucleotide repeat polymorphism at D15S976 and schizophrenia was
      investigated using two independent samples from the Han Chinese population. In a
      population-based study, no significant difference was found between the genotype
      and allele frequency distributions in schizophrenia patients and control
      subjects. In a family-based study, no significant transmission disequilibrium
      from heterozygous parents to affected offspring was observed. Further analysis of
      the parent-of-origin effect found nominally significant allele-wise transmission
      disequilibrium through maternal transmissions, while 157bp and 159bp alleles
      showed significant individual allelic transmission disequilibrium from
      heterozygous mothers to affected offspring. Our results did not support the
      hypothesis that the (TG)n dinucleotide repeat polymorphism plays a major role in
      schizophrenia susceptibility in the Chinese population. Further studies are
      needed to elucidate the putative parent-of-origin effect and its role in
      schizophrenia susceptibility.

PMID- 18346795
TI  - Head and neck epithelioid sarcoma in a child: diagnostic dilemma and
      anterolateral thigh free flap reconstruction.
AB  - The diagnostic dilemma is discussed of a child who presented with a granulomatous
      process of the external ear that was originally considered granuloma annulare and
      was later diagnosed as epithelioid sarcoma. We present the surgical treatment and
      the first report of reconstruction of a lateral skull base and cheek defect with
      an anterolateral thigh (ALT) free flap in a pediatric patient.

PMID- 18346796
TI  - An advantageous method utilizing new homogenizing device BioMasher and a
      sensitive ELISA to detect bovine spongiform encephalopathy accurately in brain
      tissue.
AB  - A new screening method was developed to detect bovine spongiform encephalopathy
      (BSE). This method is advantageous because it has a simpler and safer protocol
      than commercial kits. A new device was developed for this method; it was named
      the BioMasher, to homogenize brain tissue by passing it through a porous rigid
      polypropylene filter. In this system, a purification step was eliminated in the
      sample preparation. Thus, the time needed for sample pretreatment is
      substantially shortened, and the risk of infection during sample processing is
      effectively reduced. Monoclonal antibodies to prion protein were created and used
      to construct a sensitive sandwich enzyme-linked immunosorbent assay system. The
      sensitivity of this assay kit using frozen BSE-positive brain is comparable or
      more sensitive than commercial kits. Moreover, the detection sensitivity for
      deteriorated samples, which were kept at 37 degrees C for 1 day, is 10- to 30
      fold more sensitive than a commercial kit.

PMID- 18346797
TI  - Memory and exploratory impairment in mice that lack the Park-2 gene and that over
      express the human FTDP-17 mutant Tau.
AB  - While mutations in the Park-2 gene are the most frequent cause of autosomal
      recessive juvenile parkinsonism (AR-JP), they are also present in several forms
      of tauopathies. Conversely, in some forms of parkinsonism, mutations in the tau
      gene have also been observed. Deletion of the Park-2 gene and over-expression of
      mutant tau independently produce mild brain alterations in mice. However, the
      presence of both mutations simultaneously causes a tau neuropathology, involving
      reactive astrocytosis, neuron loss in the cortex and hippocampus, and lesions in
      nigrostriatal and motor neurons. Furthermore, mutant tau over-expression in mice
      produces important memory impairment. When "parkin" function was abolished in
      young tau transgenic mice, the memory alterations were exaggerated. Moreover,
      additional exploratory and motor deficits were observed in older mice, causing
      the memory alterations to be underestimated. Thus, while memory deficits are more
      severe in young mice they were somehow attenuated by exploratory impairments in
      ageing mutants. This double mutant animal will serve as a useful experimental
      tool to investigate the abnormal processing of hyperphosphorylated tau and its
      relationship to the development of the cognitive deficits associated with certain
      neurodegenerative diseases.

PMID- 18346798
TI  - Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks
      the M2 muscarinic acetylcholine receptor subtype.
AB  - The neurotransmitter acetylcholine is an important modulator of cognitive
      functions including attention, learning, and memory. The actions of acetylcholine
      are mediated by five distinct muscarinic acetylcholine receptor subtypes (M(1)
      M(5)). The lack of drugs with a high degree of selectivity for these subtypes has
      impeded the determination of which subtypes mediate which components of
      cholinergic neurotransmission relevant to cognitive abilities. The present study
      examined the behavioral functions of the M(2) muscarinic receptor subtype by
      utilizing congenic C57BL/6 mice possessing a null-mutation in the M(2) muscarinic
      receptor gene (M(2)(-/-) mice). Comprehensive assessment of general health and
      the neurological function found no major differences between M(2)(-/-) and wild
      type (M(2)(+/+)) mice. In the tests of learning and memory, M(2)(-/-) mice were
      impaired in the acquisition (trials to criterion), but not the retention (72h) of
      a passive avoidance task. In a novel open field, M(2)(-/-) mice were impaired in
      between-sessions, but not within-session habituation. In a holeboard test of
      spatial memory, M(2)(-/-) mice committed more errors in working memory than
      M(2)(+/+) mice. Reference memory did not differ between the genotypes. M(2)(-/-)
      mice showed no impairments in either cued or contextual fear conditioning. These
      findings replicate and extend earlier findings in a hybrid strain and solidify
      the interpretation that the M(2) receptor plays a critical role in specific
      components of cognitive abilities.

PMID- 18346799
TI  - Toxicogenomics of water chemistry influence on chronic lead exposure to the
      fathead minnow (Pimephales promelas).
AB  - Establishment of water quality criteria (WQC), intended to protect aquatic life,
      continues to rely principally on water hardness (i.e. Ca(2+)) for lead (Pb)
      despite growing evidence that other chemical parameters also strongly influence
      toxicity. To more clearly define the water chemistry parameters mediating Pb
      toxicity, we evaluated the effects of hardness as CaSO(4) and dissolved organic
      carbon (DOC) as humic acid during chronic (150 days) exposures to the fathead
      minnow. Measured Pb concentrations ranged from 157+/-5 nM (33+/-1 microg/L) Pb in
      base water to 177+/-7 (37+/-1 microg/L) and 187+/-7 nM (39+/-1 microg/L) Pb in
      CaSO(4)- or HA-supplemented water, respectively. Fish were collected at 2, 4, 10,
      30, 63, 90 and 150 days of exposure. Traditional toxicological endpoints were
      examined alongside gene transcription analyses to help clarify the underlying
      mechanisms of Pb toxicity and to identify candidate molecular markers that might
      ultimately serve as robust indicators of exposure and effect. Addition of CaSO(4)
      did not prevent whole body Pb accumulation whereas DOC afforded strong protection
      (about half the amount accumulated by fish in base water) suggesting that
      current, hardness-based WQC are likely inaccurate for predicting chronic Pb
      effects in aquatic systems. Custom-made microarrays were co-hybridized with base
      water samples+/-Pb up to the 30 days time point. Quantitative PCR was employed to
      verify gene transcription responses and to extend analysis to the CaSO(4) and HA
      treatments and the 150 days time point. Identification of four genes by
      microarray analysis revealed clear Pb-induced responses over time: glucose-6
      phosphate dehydrogenase, glutathione-S-transferase, ferritin and beta-globin.
      Results obtained by qPCR were in strong agreement with microarray data by
      regression analysis (r(2)=0.82, slope=1.28). The associated pathways implicated
      herein for these genes provide further evidence supporting roles for anemia and
      neurological disorders in chronic Pb toxicity. Effects of water chemistry on Pb
      accumulation and gene transcription responses were in close parallel, though
      alterations in ionoregulatory and morphological endpoints were not observed.
      Whereas DOC was protective against Pb accumulation and mRNA expression changes,
      Ca(2+) was not. Additionally, several hypothesis-driven genes (ECaC, DMT-1, and
      ALA-D) were examined by qPCR but revealed either no change or small Pb-induced
      responses lacking any clear influence attributable to water chemistry. These
      findings should help pave the way toward development of a new chronic Pb BLM and
      a Pb-responsive gene transcript profile for fathead minnows, both of which would
      greatly aid future environmental monitoring and regulatory strategies for Pb.

PMID- 18346800
TI  - Use of Giardia, which appears to have a single nucleotide-sugar transporter for
      UDP-GlcNAc, to identify the UDP-Glc transporter of Entamoeba.
AB  - Nucleotide-sugar transporters (NSTs) transport activated sugars (e.g. UDP-GlcNAc)
      from the cytosol to the lumen of the endoplasmic reticulum or Golgi apparatus
      where they are used to make glycoproteins and glycolipids. UDP-Glc is an
      important component of the N-glycan-dependent quality control (QC) system for
      protein folding. Because Entamoeba has this QC system while Giardia does not, we
      hypothesized that transfected Giardia might be used to identify the UDP-Glc
      transporter of Entamoeba. Here we show Giardia membranes transport UDP-GlcNAc and
      have apyrases, which hydrolyze nucleoside-diphosphates to make the antiporter
      nucleoside-monophosphate. The only NST of Giardia (GlNst), which we could
      identify, transports UDP-GlcNAc in transfected Saccharomyces and is present in
      perinuclear and peripheral vesicles and increases in expression during
      encystation. Entamoeba membranes transport three nucleotide-sugars (UDP-Gal, UDP
      GlcNAc, and UDP-Glc), and Entamoeba has three NSTs, one of which has been shown
      previously to transport UDP-Gal (EhNst1). Here we show recombinant EhNst2
      transports UDP-Glc in transfected Giardia, while recombinant EhNst3 transports
      UDP-GlcNAc in transfected Saccharomyces. In summary, all three NSTs of Entamoeba
      and the single NST of Giardia have been molecularly characterized, and
      transfected Giardia provides a new system for testing heterologous UDP-Glc
      transporters.

PMID- 18346801
TI  - Emergency department (ED) utilization of oldest old men in a veterans care home
      in Taiwan.
AB  - ED is a common channel for older people to seek for medical services. However,
      unlike most care homes in the world, veterans care home in Taiwan has a
      constantly operating outpatient and inpatient services. Therefore, utilization of
      ED services among veterans care home may be different from most care home
      residents. Records of residents in Banciao Veterans Home residents visiting the
      ED of Taipei Veterans General Hospital from January to December of 2006 were
      retrospectively collected and analyzed. Demographic variables including age, sex,
      modes of arrival, category of triage, time of visit, main presenting symptoms,
      principal diagnosis, medical expenditure and the disposition after the ED visit
      or after admission to wards were carefully recorded. In total, 368 residents
      (mean age=81.9+/-5.9 years, all men) with 635 visits were identified. Nearly a
      half of Banciao Veterans Home residents had visited ED for at least once in 2006
      and the medical expenditure was four times higher than other ED visitors. In
      average, 52.3% of ED visitors would be hospitalized and the most common diagnosis
      was infectious conditions. Onsite primary care geriatricians may play an
      important role in such settings.

PMID- 18346802
TI  - A new growth medium for rapid selection and purification of Clostridium
      proteoclasticum transposon mutants.
AB  - Clostridium proteoclasticum is commonly associated with the rumen microflora of
      pasture-fed cattle and sheep and has significant hemicellulose degradation
      abilities. Genes involved in plant fibre breakdown are commonly identified by
      producing site-specific mutations. However, the genetics of C. proteoclasticum
      and other closely-related Butyrivibrio/Pseudobutyrivibrio species is not well
      established. Therefore random transposon mutants of C. proteoclasticum were
      generated by conjugation with Enterococcus faecalis containing Tn916. A new
      counter-selection agar medium was developed containing L-arabinose and D
      raffinose as carbon sources, both of which are utilized by C. proteoclasticum
      only, and also ciprofloxacin, an antibiotic that suppresses the growth of E.
      faecalis. With this new medium the enhanced growth and more rapid separation of
      C. proteoclasticum transposon mutants from the background of E. faecalis cells
      was made, thereby facilitating the selection of transposon mutants and the
      identification of their Tn916 insertion sites.

PMID- 18346803
TI  - Chemogenomics and biotechnology.
AB  - A robust knowledge of the interactions between small molecules and specific
      proteins aids the development of new biotechnological tools and the
      identification of new drug targets, and can lead to specific biological insights.
      Such knowledge can be obtained through chemogenomic screens. In these screens,
      each small molecule from a chemical library is applied to each cell type from a
      library of cells, and the resulting phenotypes are recorded. Chemogenomic screens
      have recently become very common and will continue to generate large amounts of
      data. The interpretation of this data will occupy biologists and chemists alike
      for some time to come. This review discusses methods for the acquisition and
      interpretation of chemogenomic data, in addition to possible applications of
      chemogenomics in biotechnology.

PMID- 18346804
TI  - Validity of the motor observation questionnaire for teachers as a screening
      instrument for children at risk for developmental coordination disorder.
AB  - This study investigates validity of the Motor Observation Questionnaire for
      Teachers (MOQ-T) in 182 children aged 5-10years, 91 children referred for motor
      problems to a rehabilitation center and 91 comparison children. Performance on
      the MOQ-T was compared to performance on the Movement Assessment Battery for
      Children (M-ABC) and the Developmental Coordination Disorder Questionnaire (DCD
      Q). Significant correlations were obtained between the MOQ-T and the DCD-Q (r=
      .63), and the MOQ-T and the M-ABC (r=.57). The MOQ-T discriminated between
      children at risk for DCD and comparison children. Sensitivity of the MOQ-T was
      80.5%, specificity 62% with the M-ABC as 'gold standard'. These results support
      the validity of the MOQ-T as a screening instrument for identification of
      children at risk for DCD.

PMID- 18346805
TI  - Parameters of optic nerve electrical stimulation affecting neuroprotection of
      axotomized retinal ganglion cells in adult rats.
AB  - We previously showed the enhancement of survival of retinal ganglion cells (RGCs)
      by electrical stimulation (ES) of the optic nerve (ON) stump in adult rats. To
      elucidate the mechanisms underlying the survival enhancement, we determined
      whether the neuroprotective effect of ES is affected by the following parameters:
      stimulation time, frequency of current pulses and starting of ES. ES for 10min
      immediately after ON transection was not effective in increasing the number of
      surviving RGCs 7 days after the transection, but that for 30min was effective. ES
      at 20Hz was the most effective, when applied just after axotomy. When the
      starting of ES to the ON was shifted either 3h after or 4h before the axotomy,
      the neuroprotective effect of ES was not observed. These results suggest that the
      electrical activation of RGCs and/or the transected ON interfere with early
      events after axotomy that leads to RGC death.

PMID- 18346806
TI  - Antitumoral activity of PEG-gemcitabine prodrugs targeted by folic acid.
AB  - Gemcitabine, 2',2'-difluoro-2'-deoxycytidine (dFdC), is an antitumor agent
      effective in the treatment of several solid tumors but its use is hampered by
      short plasma half-life, rapid metabolism and low selectivity towards tumor
      tissue. To overcome these limits, bioconjugates of gemcitabine were studied using
      poly(ethylene glycol) as polymeric carrier. Two types of conjugates were
      prepared, non-targeted and folic acid targeted conjugates. The formers were
      obtained starting from mPEG-OH of 5 and 20 kDa with linear or branched structure.
      The folic acid targeted conjugates, differing for the drug loading, were prepared
      exploiting a heterobifunctional PEG that allowed a consecutive coupling of the
      targeting agent and the drug. Folic acid was chosen as targeting agent because
      its receptor is often over-expressed in many tumors. To increase the polymer drug
      payload, the bicarboxylic amino acid, aminoadipic acid, was used. All conjugates
      were able to release the drug in a pH-dependent manner with no role of enzymes.
      The pharmacokinetic profiles are strictly related to the polymer molecular weight
      and the folic acid targeting increased 2-3 times the affinity towards the cells
      over-expressing folic acid receptors. These results are promising and encourage
      in vivo studies on these conjugates that act as polymeric prodrugs.

PMID- 18346807
TI  - Poly(imidazole/DMAEA)phosphazene/DNA self-assembled nanoparticles for gene
      delivery: synthesis and in vitro transfection.
AB  - A new cationic derivate of polyphosphazene with imidazole and 2
      dimethylaminoethylamino (DMAEA) as side groups, poly(imidazole/DMAEA)phosphazene
      (PIDP), was synthesized and investigated for gene delivery. The half-lives of
      PIDP degradation under neutral (pH 7.4) and acidic conditions (pH 5.0) were 22
      and 3 days at 37 degrees C, respectively. The cytotoxicity of PIDP assayed by MTT
      was much lower than that of poly(2-dimethylaminoethylamino)phosphazene (PDAP) and
      PEI 25K. PIDP could condense DNA into nanoparticles with a size around 100 nm and
      zeta potential (+25 mV) at the ratio of 10:1 (PIDP/DNA, w/w). The transfection
      efficiency of PIDP/DNA complex nanoparticles (PICNs) against 293T, COS-7 and Hela
      cells was much higher than that of PDAP/DNA complexes nanoparticles (PDCNs) and
      PEI/DNA complexes nanoparticles (PECNs) at 10:1 (polymer/DNA, w/w). Therefore,
      PIDP could be a safe, efficient and promising cationic polymer for gene therapy.

PMID- 18346808
TI  - [Ischemic bilateral lumbosacral plexopathy and walking disability following
      surgical treatment of secondary aortoenteric fistulas: a case report and review
      of literature].
AB  - OBJECTIVE: Aortoenteric fistula is a rare and serious pathology with a high
      mortality rate (around 50%). The surgery's neurological complications are also
      rare (around 0.25% of reconstructive interventions); two-thirds are spinal cord
      infarcts, with the remaining one-third corresponding to cases of ischemic
      polyradiculopathy. The latter condition is rarely described and appears to have a
      better functional prognosis. METHODOLOGY: We report a patient case with
      aortoduodenal fistula complicated, first by acute haemorrhage and then, by
      polyradicular damage and a sensorimotor impairment in both legs. RESULTS: EMG
      revealed bilateral damage to the lumbosacral plexus but NMR did not detect any
      abnormalities. The motor impairment in the legs was linked to sensory damage. We
      monitored the patient for two years. The initial functional disability score was
      68 but it worsened steadily to a maximum value of 126 two years later.
      CONCLUSION: The paraclinical data (EMG, NMR) and the functional worsening
      strengthened our diagnosis of bilateral lumbosacral plexus ischemia, which is
      rarely described. However, the prognosis appears to be better than for infarction
      of the conus medullaris, the principal differential diagnosis.

PMID- 18346809
TI  - Mutations in the beta1 adrenergic receptor gene and massive obesity in Japanese.
AB  - Catecholamines strongly promote lipolysis and thermogenesis, and play a central
      role in the regulation of body fat content. The beta1 adrenergic receptor (BAR-1)
      is a major mediator of catecholamine-induced lipolysis and thermogenesis. To
      explore whether mutations in the BAR-1 gene contribute to morbid obesity in
      Japanese, we scanned for mutations in the coding sequence of the gene in 50
      morbid obese [body mass index (BMI)>==35.0kg/m(2); 99.7th percentile] Japanese
      subjects. Direct DNA sequencing was performed following polymerase chain reaction
      (PCR) amplification. Two common polymorphisms, Gly49Arg and Arg389Ser, were
      detected in these subjects. The frequencies of these polymorphisms, as determined
      by PCR-restriction fragment length polymorphism (RFLP) analysis, showed no
      significant difference between 180 severely obese subjects (BMI>==30.0kg/m(2);
      97th percentile) and 132 control (BMI<25.0kg/m(2)) subjects. This study
      represents the first investigations of genetic variations of BAR-1 in
      relationship to morbid obesity and suggests mutations in the BAR-1 coding
      sequence is not likely a major cause of morbid obesity at least in Japanese.

PMID- 18346810
TI  - Endothelin-1 levels and albuminuria in patients with type 2 diabetes mellitus.
AB  - AIM: To evaluate the relationship of plasma endothelin-1 (ET-1) levels, a marker
      of endothelial dysfunction, and urinary albumin excretion in patients with type 2
      diabetes mellitus (DM). METHODS: Cross-sectional study was conducted in 279
      patients (132 males, mean age: 58.7+/-11.0 years, mean DM duration: 11.3+/-8.1
      years). Urinary albumin excretion, ET-1, and insulin were measured. Insulin
      sensitivity was estimated by homeostasis model assessment (HOMA-ir) index.
      RESULTS: ET-1 was associated with urinary albumin excretion after controlling for
      age, gender, body mass index, blood pressure, HbA1c test, and total cholesterol
      (R=0.436; adjusted R(2)=0.190, P<0.01). Furthermore, there was a progressive
      increase in plasma ET-1 levels from patients with normoalbuminuria (n=187, 0.92+/
      0.50pg/ml), microalbuminuria (n=68, 1.13+/-0.52pg/ml) to macroalbuminuria (n=24,
      1.93+/-1.10pg/ml, P<0.01). CONCLUSION: There is an independent association of
      plasma ET-1 levels with urinary albumin excretion. In addition, plasma ET-1
      levels started to increase in the normal values of urinary albumin excretion
      suggesting that in patients with type 2 DM endothelial dysfunction is already
      present, in urinary albumin excretion values considered normal.

PMID- 18346811
TI  - Efficacy of pioglitazone on type 2 diabetic patients with hemodialysis.
AB  - AIMS: Unfortunately, growing number of type 2 diabetic hemodialysis (HD) patients
      with insulin resistance are now being diagnosed in Japan. Worse still,
      PPARgammaagonists such as pioglitazone are now contraindicated in diabetic HD
      patients in Japan. In this study we evaluated the efficacy of pioglitazone in
      diabetics on HD. METHODS: Following a 12-week baseline period, we enrolled a
      study population of poorly controlled diabetic HD patients who had mean
      hemoglobin A1c (HbA1c) levels greater than 6.5% at baseline and who were not
      receiving insulin injection therapy. The patients were administered pioglitazone
      15mg daily with their morning meal for the first 4 weeks. Subsequently, the doses
      were titrated by dose-doubling to a maximum of 30mg/day if no adverse effects
      appeared. The efficacy was determined by monitoring glycemic control (plasma
      glucose and HbA1c), and insulin resistance (plasma immunoreactive insulin (IRI)
      and homeostasis model assessment for insulin resistance (HOMA-R)). Safety and
      tolerance were determined by monitoring clinical and laboratory parameters.
      RESULTS: Pioglitazone was effective in reducing plasma glucose and HbA1c from the
      baseline levels from week 4 after the commencement of treatment. The agent was
      also effective in reducing triglycerides. Plasma IRI and HOMA-R, two parameters
      of insulin resistance, decreased significantly at 4 weeks, and the decreases
      continued for 24 weeks. Systolic and diastolic blood pressures were statistically
      lower at 8 weeks. No serious adverse effects such as hypoglycemia, liver
      impairment, or rhabdomyolysis were observed in any of the patients. CONCLUSIONS:
      Pioglitazone was effective in the treatment of diabetics on dialysis therapy.
      Pioglitazone might have the potential to reduce the number of type 2 diabetics on
      HD who ultimately require insulin injection therapy.

PMID- 18346812
TI  - Automated speech analysis applied to laryngeal disease categorization.
AB  - The long-term goal of the work is a decision support system for diagnostics of
      laryngeal diseases. Colour images of vocal folds, a voice signal, and
      questionnaire data are the information sources to be used in the analysis. This
      paper is concerned with automated analysis of a voice signal applied to screening
      of laryngeal diseases. The effectiveness of 11 different feature sets in
      classification of voice recordings of the sustained phonation of the vowel sound
      /a/ into a healthy and two pathological classes, diffuse and nodular, is
      investigated. A k-NN classifier, SVM, and a committee build using various
      aggregation options are used for the classification. The study was made using the
      mixed gender database containing 312 voice recordings. The correct classification
      rate of 84.6% was achieved when using an SVM committee consisting of four
      members. The pitch and amplitude perturbation measures, cepstral energy features,
      autocorrelation features as well as linear prediction cosine transform
      coefficients were amongst the feature sets providing the best performance. In the
      case of two class classification, using recordings from 79 subjects representing
      the pathological and 69 the healthy class, the correct classification rate of
      95.5% was obtained from a five member committee. Again the pitch and amplitude
      perturbation measures provided the best performance.

PMID- 18346813
TI  - Winter photosynthetic activity of twenty temperate semi-desert sand grassland
      species.
AB  - The winter photosynthetic activity (quantified by net CO(2) assimilation rates
      and chlorophyll (Chl) a fluorescence parameters) of 20 plant species (including
      two lichens and two mosses) of a Hungarian temperate semi-desert sand grassland
      was determined on one occasion per year in 1984, 1989 and 1994. Throughout
      winter, the overwintering green shoots, leaves or thalli were regularly exposed
      to below zero temperatures at night and daytime temperatures of 0-5 degrees C. In
      situ tissue temperature varied between -2.1 and +6.9 degrees C and the
      photosynthetic photon flux density (PPFD) between 137 and 351 micromol m(-2)s(
      1). Under these conditions 18 of the grassland species exhibited photosynthetic
      CO(2) uptake (range: vascular plants ca. 0.2-3.8 micromol m(-2)s(-1), cryptogams
      0.3-2.79 micromol kg(-1)s(-1)) and values of 0.9-5.1 of the Chl fluorescence
      decrease ratio R(Fd). In 1984, Festuca vaginata and Sedum sexangulare had net
      CO(2) assimilation at leaf temperatures of -0.85 to -1.2 degrees C. In 1989, all
      species except Cladonia furcata showed net CO(2) assimilation at tissue
      temperatures of 0 to +3.3 degrees C, with the highest rates observed in Poa
      bulbosa and F. vaginata. The latter showed a net CO(2) assimilation saturation at
      a PPFD of 600 micromol m(-2)s(-1) and a temperature optimum between +5 and +18
      degrees C. At the 1994 measurements, the photosynthetic rates were higher at
      higher tissue water contents. The two mosses and lichens had a net photosynthesis
      (range: 1.1-2.79 micromol CO(2)kg(-1)s(-1)) at 2 degrees C tissue temperature and
      at 4-5 degrees C air temperature. Ca. 80% of the vascular grassland plant species
      maintained a positive C-balance during the coldest periods of winter, with
      photosynthetic rates of 1.5-3.8 micromol CO(2)m(-2)s(-1). In an extremely warm
      beginning March of the relatively warm winter of 2006/2007, the dicotyledonous
      plants had much higher CO(2) assimilation rates on a Chl (range 6-14.9 micromol
      g(-1)Chl s(-1)) and on a dry weight basis (9-48 micromol kg(-1)dw s(-1)) than in
      the cold winter of 1994. However, the assimilation rates of the three
      investigated cryptogams (Tortula and two Cladonia) and the two grasses Festuca
      and Poa were not affected by this increase. The results indicate that the
      photosynthetic activity of temperate semi-desert sand grassland species can help
      somewhat in slowing the general CO(2) rise in winter and function as a potential
      carbon sink of the investigated semi-desert Hungarian grassland species.

PMID- 18346814
TI  - Application of the forensic Luminol for blood in infection control.
AB  - Transmission of hepatitis C virus occurs frequently in haemodialysis units. A
      possible route of transmission is indirectly via the hospital environment
      although this has never been recorded. We investigated the haemodialysis unit in
      Deventer Hospital, Deventer, The Netherlands, with the forensic Luminol test.
      With this test, invisible traces of blood can be visualised based on the
      principle of biochemiluminescence. We demonstrated extensive contamination of the
      environment with traces of blood. The aim of this article is to introduce this
      method to infection control professionals, so it can be used to monitor cleaning
      and disinfection procedures, and alert healthcare workers to the possibility of
      contamination of the hospital environment with blood.

PMID- 18346815
TI  - First point prevalence survey of nosocomial infections in the intensive care
      units of a tertiary care hospital in Albania.

PMID- 18346816
TI  - Outbreak of ciprofloxacin-susceptible community-associated meticillin-resistant
      Staphylococcus aureus in a neonatal unit.

PMID- 18346817
TI  - Central and peripheral administration of amylin induces energy expenditure in
      anesthetized rats.
AB  - Amylin is a peptide hormone that is co-released with insulin from pancreatic beta
      cells following a meal. Intracerebroventricular (icv) administration of amylin (1
      100 pmol), or an amylin agonist, salmon calcitonin, elicited dose-dependent
      thermogenic, tachycardic, and hyperthermic responses in urethane-anesthetized
      rats. Intravenous (iv) administration of higher doses of amylin (100 pmol-20
      nmol) also induced similar responses, although the amplitudes of these responses
      were significantly smaller than those elicited by icv administration, suggesting
      the primary action of amylin to be in the brain. However, the iv administration
      of amylin induced the responses slightly faster than the icv injection, the
      former responses occurring<4 min and the latter, at 8-10 min, after the
      administration. The iv but not the icv injection of amylin increased the
      respiratory exchange ratio transiently (<20 min), though the thermogenic response
      lasted for a longer period after both injections, indicating a shift from mixed
      fuel to predominantly carbohydrate utilization in the initial phase of
      thermogenesis induced by the iv injection of amylin. The differences in substrate
      utilization and latency of the responses suggest that the actions of amylin
      include partly different targets when administered centrally and peripherally.
      Moreover, pretreatment with a beta-adrenergic blocker, propranolol (5 mg kg(-1),
      iv), blocked all responses elicited by either icv or iv administration of amylin,
      whereas ablation of the area postrema in the hindbrain did not influence the
      effects of icv-administered amylin. These results suggest the involvement of
      amylin in postprandial energy expenditure, mediated by peripheral beta
      adrenoceptors.

PMID- 18346818
TI  - Effects of ghrelin on neuronal activity in the ventromedial nucleus of the
      hypothalamus in infantile rats: an in vitro study.
AB  - Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue (GHS)
      receptor (GHS-R) and a potent stimulant for GH secretion even in infantile rats
      before puberty. Although the ventromedial nucleus of the hypothalamus (VMH) might
      be a site of action for ghrelin to induce GH release, the electrophysiological
      effect of ghrelin on VMH neurons in infantile rats remains to be elucidated.
      Thus, the purpose of the present study was to investigate the effect of ghrelin
      on VMH neurons using hypothalamic slices of infantile rats. Ghrelin excited a
      majority of VMH neurons in a concentration-dependent manner. VMH neurons that
      were excited by GH releasing peptide-6 (GHRP-6), a synthetic GHS, were also
      excited by ghrelin and vice versa. Repeated application of ghrelin to the same
      VMH neuron decreased progressively the excitatory responses depending on the
      number of times it was administered. The excitatory effect of ghrelin on VMH
      neurons in normal artificial cerebrospinal fluid (ACSF) persisted in low Ca2+
      high Mg2+ ACSF. The present results indicate that (1) ghrelin excites a majority
      of VMH neurons dose-dependently and postsynaptically and (2) the excitatory
      effects of ghrelin are mimicked by GHRP-6 and desensitized by repeated
      applications of ghrelin.

PMID- 18346819
TI  - Increases in cholinergic neurotransmission measured by using choline-sensitive
      microelectrodes: enhanced detection by hydrolysis of acetylcholine on recording
      sites?
AB  - Previous experiments demonstrated that second-based transient increases in
      choline concentrations measured by electrodes coated with choline oxidase (ChOx)
      and the amperometric detection of hydrogen peroxide validly indicate the
      depolarization-dependent release of acetylcholine (ACh) and its hydrolysis by
      endogenous acetylcholinesterase (AChE). Therefore, choline-sensitive
      microelectrodes have become valuable tools in neuropharmacological and behavioral
      research. The present experiments were designed to test the possibility that co
      immobilization of ChOx plus AChE on recording sites increases the level of
      detection for evoked ACh release in the brain. If newly released ACh is not
      completely hydrolyzed by endogenous AChE and capable of reaching the
      extracellular space, currents recorded via sites equipped with both enzymes
      should be greater when compared with sites coated with ChOx only. Pairs of
      platinum-recording sites were coated either with AChE plus ChOx or ChOx alone.
      Potassium or nicotine-evoked currents were recorded throughout the entire dorsal
      ventral extent of the medial prefrontal cortex (mPFC). The amplitudes of evoked
      cholinergic signals did not differ significantly between AChE+ChOx and ChOx-only
      coated recording sites. Additional experiments controlling for several potential
      confounds suggested that, in vivo, ACh levels > or =150fmol were detected by
      recordings sites featuring dual enzyme coating. Collectively, these results
      indicate that co-coating of microelectrodes with AChE does not enhance the
      detection of cholinergic activity in the cortex compared with measurements via
      recording sites coated only with ChOx.

PMID- 18346820
TI  - A meta-analysis of hippocampal atrophy rates in Alzheimer's disease.
AB  - Hippocampal atrophy rates are useful in both diagnosing and tracking Alzheimer's
      disease (AD). However, cohorts and methods used to determine such rates are
      heterogeneous, leading to differences in reported annualised rates. We performed
      a meta-analysis of hippocampal atrophy rates in AD patients and matched controls
      from studies reported in the peer-reviewed literature. Studies reporting
      longitudinal volume change in hippocampi in AD subjects together with controls
      were systematically identified and appraised. All authors were contacted either
      to confirm the results or to provide missing data. Meta-analysis and meta
      regression were then performed on this data. Nine studies were included from
      seven centres, with data from a total of 595 AD and 212 matched controls. Mean
      (95% CIs) annualised hippocampal atrophy rates were found to be 4.66% (95% CI
      3.92, 5.40) for AD subjects and 1.41% (0.52, 2.30) for controls. The difference
      between AD and control subject in this rate was 3.33% (1.73, 4.94).

PMID- 18346821
TI  - Clinical severity of Alzheimer's disease is associated with PIB uptake in PET.
AB  - BACKGROUND: The positron emission tomography (PET) tracer [11C]-Pittsburgh
      Compound-B ([11C]PIB) allows the in vivo assessment of amyloid plaque burden in
      the brain. In a cross-sectional study we examined the association between the
      severity of dementia assessed using the Clinical Dementia Rating scale sum of
      boxes (CDR-SOB) and [11C]PIB-PET in patients with Alzheimer's disease (AD).
      METHODS: Patients with probable AD who had an AD-typical [18F]FDG-PET scan were
      included. Linear regression analysis in anatomically defined regions-of-interest
      (ROIs) and correlation analysis using statistical parametric mapping (SPM) were
      used to determine the association between CDR-SOB and [11C]PIB uptake. RESULTS:
      The linear regression analyses showed that the CDR-SOB explained approximately 11
      22% of the variance of [11C]PIB uptake. The association attained statistical
      significance in both frontal, in both anterior cingulate cortices, and in both
      putamina. The SPM analysis showed a significant association in more widespread
      regions of the brain, with maxima located in similar areas as in the ROI
      analysis. CONCLUSION: The CDR-SOB score is significantly associated with [11C]PIB
      uptake in patients with AD. Thus [11C]PIB is a potential surrogate marker of
      dementia severity.

PMID- 18346822
TI  - 3D and quantum QSAR of non-benzodiazepine compounds.
AB  - A combined physicochemical and 3D technique is used to establish the QSAR of four
      series of non-benzodiazepines towards BzR. In physicochemical QSAR study, the
      semi-empirical PM3 based parameters like hardness, electronegativity,
      electrophilicity index, molar refractivity, heat of formation, solvent assessable
      surface area and logP were used as descriptors. The heat of formation (HF) and
      logP are recognized as the most important descriptors for binding affinity of
      such compounds to BzR. The 3D QSAR study reveals that beta-Carbolines of series
      "A" and Imidazo[1, 2-alpha]pyrimidines of series "C" show steric bulk
      interaction, the beta-Carbolines of series "B" and di-substituted purines of
      series "D" have dominance of electrostatic interaction with BzR. The CoMSIA also
      indicate the same trend in terms of steric and electrostatic interaction. The
      CoMSIA reveals that only in case of series "D", the hydrophobic field effect is
      important. Some possible candidates for all four series were designed and their
      probable activities were estimated by using different QSAR models. The activities
      of designed molecules are in better range and developed models might be helpful
      to design the potent ligands of BzR.

PMID- 18346823
TI  - Induction of neutralising antibodies and cellular immune responses against SARS
      coronavirus by recombinant measles viruses.
AB  - Live attenuated recombinant measles viruses (rMV) expressing a codon-optimised
      spike glycoprotein (S) or nucleocapsid protein (N) of severe acute respiratory
      syndrome-associated coronavirus (SARS-CoV) were generated (rMV-S and rMV-N). Both
      recombinant viruses stably expressed the corresponding SARS-CoV proteins, grew to
      similar end titres as the parental strain and induced high antibody titres
      against MV and the vectored SARS-CoV antigens (S and N) in transgenic mice
      susceptible to measles infection. The antibodies induced by rMV-S had a high
      neutralising effect on SARS-CoV as well as on MV. Moreover, significant N
      specific cellular immune responses were measured by IFN-gamma ELISPOT assays. The
      pre-existence of anti-MV antibodies induced by the initial immunisation dose did
      not inhibit boost of anti-S and anti-N antibodies. Immunisations comprising a
      mixture of rMV-S and rMV-N induced immune responses similar in magnitude to that
      of vaccine components administered separately. These data support the suitability
      of MV as a bivalent candidate vaccine vector against MV and emerging viruses such
      as SARS-CoV.

PMID- 18346824
TI  - A vaccine prepared from a non-pathogenic H7N7 virus isolated from natural
      reservoir conferred protective immunity against the challenge with lethal dose of
      highly pathogenic avian influenza virus in chickens.
AB  - During 2001-2004, 41 H7 influenza viruses (2 H7N1 and 39 H7N7 strains) were
      isolated from fecal samples of migratory ducks that flew from Siberia in the
      autumn of each year to Japan and Mongolia. A phylogenetic analysis of the
      hemagglutinin (HA) genes of the nine representative isolates revealed that they
      belonged to the Eurasian lineage and the deduced amino acid sequence at the
      cleavage site of the HAs represented apathogenic profiles. One of the H7 isolates
      A/duck/Mongolia/736/02 (H7N7) was chosen from these H7 isolates for the
      preparation of the test vaccine. To improve the growth potential of
      A/duck/Mongolia/736/02 (H7N7) in chicken embryos, A/duck/Hokkaido/Vac-2/04 (H7N7)
      was generated by genetic reassortment between A/duck/Mongolia/736/02 (H7N7) as
      the donor of the PB2, PB1, PA, HA, NA, and NS genes and A/duck/Hokkaido/49/98
      (H9N2) as that of NP and M genes. The test vaccine was prepared as follows;
      A/duck/Hokkaido/Vac-2/04 (H7N7) was propagated in chicken embryos and the virus
      in the allantoic fluid was inactivated and adjuvanted to form an oil-in-water
      emulsion. The test vaccine conferred immunity to chickens, completely protecting
      the manifestation of clinical signs against the challenge with lethal dose of H7
      highly pathogenic avian influenza virus. These results indicate that influenza
      viruses isolated from natural reservoirs are useful for vaccine strains.

PMID- 18346825
TI  - Meige syndrome: a rare form of cranial dystonia that was treated successfully
      with botulinum toxin.
AB  - Meige syndrome, a rare form of cranial dystonia, is characterised by bilateral
      involuntary activity of facial and perioral muscles combined with blepharospasms.
      A case of a 15-year-old boy with Meige syndrome who was managed with injection of
      botulinum toxin is presented.

PMID- 18346826
TI  - Midwives and nurses awareness of patients' rights.
AB  - AIM: to determine the level of awareness of patients' rights among midwives and
      nurses working in the third and fourth largest cities in Turkey. METHODS: cross
      sectional descriptive survey conducted among participants working in university
      hospitals, state hospitals and village clinics. Questionnaires were distributed
      to 150 midwives and 350 nurses working in university hospitals (n = 200), state
      hospitals (n = 100) and village clinics (n = 100); 60% (n = 298) of the forms
      were returned. FINDINGS: fifty-one per cent (n = 152) of midwives and nurses
      stated that they had not read any legislation related to patients' rights.
      Seventy-five per cent (n = 222) of respondents were aware of the legal
      arrangements. Only 34% (n = 74) of participants who knew of any legal basis for
      patients' rights said that legislation was in the form of a directive. No
      significant differences were observed in midwives' answers compared with nurses'
      answers. CONCLUSION: violation of patients' rights and health professionals'
      ignorance of appropriate practice means that there is an urgent need to
      reconsider how to approach this issue. It should be included in continuing
      education programmes at both graduate and postgraduate midwifery and nursing
      schools, and also demands more research.

PMID- 18346827
TI  - Mechanical factors relate to pain in knee osteoarthritis.
AB  - BACKGROUND: Pain experienced by people with knee osteoarthritis is related to
      psychosocial factors and damage to articular tissues and/or the pain pathway
      itself. Mechanical factors have been speculated to trigger this pain experience;
      yet mechanics have not been identified as a source of pain in this population.
      The purpose of this study was to identify whether mechanics could explain
      variance in pain intensity in people with knee osteoarthritis. METHODS: Data from
      53 participants with physician-diagnosed knee osteoarthritis (mean age=68.5
      years; standard deviation=8.6 years) were analyzed. Pain intensity was reported
      on the Western Ontario and McMaster Universities Osteoarthritis Index. Mechanical
      measures included weight-bearing varus-valgus alignment, body mass index and
      isokinetic quadriceps torque. Gait analysis captured the range of adduction
      abduction angle, range of flexion-extension angle and external knee adduction
      moment during level walking. FINDINGS: Pain intensity was significantly related
      to the dynamic range of flexion-extension during gait and body mass index. A
      total of 29% of the variance in pain intensity was explained by mechanical
      variables. The range of flexion-extension explained 18% of variance in pain
      intensity. Body mass index added 11% to the model. The knee adduction moment was
      unrelated to pain intensity. INTERPRETATION: The findings support that mechanical
      factors are related to knee osteoarthritis pain. Because limitations in flexion
      extension range of motion and body size are modifiable factors, future research
      could examine whether interventions targeting these mechanics would facilitate
      pain management.

PMID- 18346828
TI  - Accumulation of selenium in aquatic systems downstream of a uranium mining
      operation in northern Saskatchewan, Canada.
AB  - The objective of this study was to investigate the accumulation of selenium in
      lakes downstream of a uranium mine operation in northern Saskatchewan, Canada.
      Selenium concentrations in sediment and biota were elevated in exposure areas
      even though water concentrations were low (<5 microg/L). The pattern (from
      smallest to largest) of selenium accumulation was: periphyton<plankton and
      filterer invertebrates<detritivore and predator invertebrates<small bodied
      (forage) fish and predatory fish. Biomagnification of selenium resulted in an
      approximately 1.5-6 fold increase in the selenium content between plankton,
      invertebrates and forage fish. However, no biomagnification was observed between
      forage fish and predatory fish. Selenium content in organisms from exposure areas
      exceeded the proposed 3-11 microg/g (dry weight) dietary toxicity threshold for
      fish, suggesting that the selenium released into these aquatic systems has the
      potential to bioaccumulate and reach levels that could impair fish reproduction.

PMID- 18346829
TI  - Mutagenicity assessment of acrylate and methacrylate compounds and implications
      for regulatory toxicology requirements.
AB  - Esters of acrylic acid and methacrylic acid, more commonly known as acrylates and
      methacrylates, respectively, are key raw materials in the coatings and printing
      industry, with several of its chemical class used in food packaging. The results
      of over 200 short-term in vitro and in vivo mutagenicity studies available in the
      open literature have been evaluated. Despite differences in acrylate or
      methacrylate functionality or in the number of functional groups, a consistent
      pattern of test response was seen in a typical regulatory battery of mutagenicity
      tests. No evidence of point mutations was observed when acrylic acid or over 60
      acrylates and methacrylates were investigated in Salmonella bacterial tests or in
      hprt mutation tests mammalian cells, and no evidence of a mutagenic effect was
      seen when tested in whole animal clastogenicity and/or aneuploidy (chromosomal
      aberration/micronucleus) studies. Consistent with the in vivo testing results,
      acrylic acid exhibited no evidence of carcinogenicity in chronic rodent cancer
      bioassays. In contrast, acrylic acid and the entire acrylate and methacrylate
      chemical class produced a consistently positive response when tested in the mouse
      lymphoma assay and/or other in vitro mammalian cell assays designed to detect
      clastogenicity. The biological relevance of this in vitro response is questioned
      based on the non-concordance of in vitro results with those of in vivo studies
      addressing the same mutagenic endpoint (clastogenicity). Thus, in short-term
      mutagenicity tests, the acrylates and methacrylates behave as a single chemical
      category, and genotoxicity behavior of a similar chemical can be predicted with
      confidence by inclusion within this chemical class, thus avoiding unnecessary
      testing.

PMID- 18346830
TI  - Microstructural integrity of the corpus callosum linked with neuropsychological
      performance in adolescents.
AB  - BACKGROUND: Diffusion tensor imaging (DTI) has revealed microstructural aspects
      of adolescent brain development, the cognitive correlates of which remain
      relatively uncharacterized. METHODS: DTI was used to assess white matter
      microstructure in 18 typically developing adolescents (ages 16-18). Fractional
      anisotropy (FA) and mean diffusion (MD) were evaluated within the splenium and
      body of the corpus callosum in relation to cognitive performance. RESULTS:
      Visuospatial construction abilities were associated with white matter integrity
      in both the splenium and body of the corpus callosum, while only splenium
      integrity was associated with language and psychomotor function. CONCLUSION:
      Results suggest that, for typically developing adolescents, white matter
      coherence positively relates to visuospatial, psychomotor, and language skills.
      These findings may have implications for the cognitive functioning of clinical
      populations in which typical white matter development is altered.

PMID- 18346831
TI  - Guided saccades modulate face- and body-sensitive activation in the
      occipitotemporal cortex during social perception.
AB  - Functional magnetic resonance imaging (fMRI) has identified distinct brain
      regions in ventral occipitotemporal cortex (VOTC) and lateral occipitotemporal
      cortex (LOTC) that are differentially activated by pictures of faces and bodies.
      Recent work from our laboratory has shown that the strong LOTC activation evoked
      by bodies in which the face is occluded is attenuated when the occlusion is
      removed. We hypothesized that this attenuation may occur because subjects
      preferentially fixate upon faces when present in the scene. Here, we
      experimentally manipulated subjects' fixations while they viewed a static picture
      of a character whose face, hand, and torso were continuously visible throughout
      each run. The subject's saccades and fixations were guided by a small fixation
      cross that made discrete jumps to a new location every 500ms. Subjects were
      instructed to follow the fixation cross and make a button press whenever it
      changed size. In a series of blocks, the fixation cross shifted from locations on
      the face, on the hand, and to locations on a background image of a phase
      scrambled face. In a second study, the fixation cross moved similarly, but the
      hand locations were changed to locations along the character's body or torso. A
      localizer task was used to identify face- and body-sensitive regions of LOTC.
      Body-sensitive regions were strongly activated when the subjects' saccades were
      guided over the character's torso relative to when the saccades were guided over
      the character's face. Little to no activity occurred in the body-sensitive region
      of LOTC when the subjects' saccades were guided over the character's hand. The
      localizer task was unable to differentiate body-sensitive regions in lateral VOTC
      from face-sensitive regions, or body-sensitive regions in medial VOTC from flower
      sensitive regions. Guided saccades over the body strongly activated both lateral
      and medial VOTC. These results provide new insights into the function of body
      sensitive visual areas in both LOTC and VOTC, and illustrate the potential
      confounding influence of uncontrolled eye movements for neuroimaging studies of
      social perception.

PMID- 18346832
TI  - Neurotransmitter, peptide and cytokine processes in relation to depressive
      disorder: comorbidity between depression and neurodegenerative disorders.
AB  - Given the array of biological changes induced by stressors, it is not surprising
      that these experiences may provoke a variety of illnesses. Among others things,
      stressors promote functional changes of neuropeptide and classical
      neurotransmitter systems. The peptidergic changes, for instance, include
      alterations of corticotropin releasing hormone, arginine vasopressin, and
      bombesin-like peptides at specific brain sites. Similarly some of the
      neurotransmitter systems influenced by stressors include GABAergic and monoamine
      functioning. Variations of these processes may limit neurogenesis (and
      dysregulation of growth factors such as BDNF) and influence cellular viability
      (through NFkappaB and MAP kinase pathways). As well, stressors activate the
      inflammatory immune system, notably the release of signaling molecules
      (cytokines), which may provoke many of the same neuropeptide (and other
      neurotransmitter) changes. By virtue of their actions on neuronal functioning,
      inflammatory processes may influence stress-related illness, such as depression,
      and may be a common denominator for the comorbidity that exists between
      depression and neurological conditions, including Parkinson's and Alzheimer's
      diseases, as well as cardiovascular-related pathology. The present report
      provides an overview of biological endophenotypes associated with stressors that
      are thought to be related to major depressive disorder and related comorbid
      conditions. The view is taken that synergy between stressors and inflammatory
      factors may promote pathological outcomes through their actions on neuropeptides
      and several neurotransmitters. As well, stressful events may result in the
      sensitization of neurochemical and cytokine processes, so that later re-exposure
      to these stimuli may promote rapid and exaggerated responses that favor illness
      recurrence.

PMID- 18346833
TI  - Respiration, metabolic balance, and attention in affective picture processing.
AB  - The respiratory behavior during affective states is not completely understood. We
      studied breathing pattern responses to picture series in 37 participants. We also
      measured end-tidal pCO2 (EtCO2) to determine if ventilation is in balance with
      metabolic demands and spontaneous eye-blinking to investigate the link between
      respiration and attention. Minute ventilation (MV) and inspiratory drive
      increased with self-rated arousal. These relationships reflected increases in
      inspiratory volume rather than shortening of the time parameters. EtCO2 covaried
      with pleasantness but not arousal. Eye-blink rate decreased with increasing
      unpleasantness in line with a negativity bias in attention. This study confirms
      that respiratory responses to affective stimuli are organized to a certain degree
      along the dimensions of valence and arousal. It shows, for the first time, that
      during picture viewing, ventilatory increases with increasing arousal are in
      balance with metabolic activity and that inspiratory volume is modulated by
      arousal. MV emerges as the most reliable respiratory index of self-perceived
      arousal.

PMID- 18346834
TI  - Structural stability and reversible unfolding of recombinant porcine S100A12.
AB  - Porcine S100A12 is a member of the S100 proteins, family of small acidic calcium
      binding proteins characterized by the presence of two EF-hand motifs. These
      proteins are involved in many cellular events such as the regulation of protein
      phosphorylation, enzymatic activity, protein-protein interaction, Ca2+
      homeostasis, inflammatory processes and intermediate filament polymerization. In
      addition, members of this family bind Zn2+ or Ca2+ with cooperative effect on
      binding. In this study, the gene sequence encoding porcine S100A12 was obtained
      by the synthetic gene approach using E. coli codon bias. Additionally, we report
      a thermodynamic study of the recombinant S100A12 using circular dichroism,
      fluorescence and isothermal titration calorimetry. The results of urea and
      temperature induced unfolding and refolding processes indicated a reversible two
      state process. Also, the ANS fluorescence studies showed that in presence of
      divalent ions the protein exposes hydrophobic sites which could facilitate the
      interaction with other proteins and trigger the physiological responses.

PMID- 18346835
TI  - G-CSF in patients suffering from late revascularized ST elevation myocardial
      infarction: analysis on the timing of G-CSF administration.
AB  - OBJECTIVE: Granulocyte colony-stimulating factor (G-CSF) improves myocardial
      function after infarction in vivo. Placebo-controlled clinical studies failed to
      show beneficial effects on myocardial function. Recent data demonstrate that the
      time point of treatment initiation may be crucial for the efficacy of G-CSF. We
      investigated the influence of the timing of G-CSF treatment on myocardial
      function and perfusion in a subgroup study of the G-CSF-ST Elevation Myocardial
      Infarction trial. MATERIALS AND METHODS: Patients with late revascularized
      myocardial infarction (n = 44) were treated with either G-CSF or placebo over 5
      days after successful percutaneous coronary intervention (PCI). Of the G-CSF
      group, 13 patients had received G-CSF early treatment started within 24 hours
      after PCI (mean: 16 +/- 6 hours). In 10 patients, G-CSF was initiated late (>24
      hours after PCI, mean: 49 +/- 26 hours). Global and regional myocardial function
      and perfusion were assessed from baseline to 3 months after PCI using magnetic
      resonance imaging in 37 patients who completed magnetic resonance follow-up.
      RESULTS: G-CSF was safe when used early or late after PCI. Early G-CSF
      administration resulted in significantly improved perfusion at rest 1 month after
      PCI when compared to placebo (Up-slope, signal intensity 1.2 [0.4-1.8] vs 0.6
      [0.1-1.3], p = 0.03). Timing of G-CSF had no influence on global and regional
      function. CONCLUSION: This post-hoc analysis indicates that timing of G-CSF after
      myocardial infarction does not improve myocardial function but myocardial
      perfusion if the cytokine is given early. This urges the need to investigate
      alternative dosage regimens or combination with novel therapeutics promoting
      mobilization and homing.

PMID- 18346836
TI  - Rapid platelet turnover in WASP(-) mice correlates with increased ex vivo
      phagocytosis of opsonized WASP(-) platelets.
AB  - OBJECTIVE: Our objective was to determine a mechanism for the thrombocytopenia of
      murine Wiskott-Aldrich syndrome (WAS). MATERIALS AND METHODS: Consumption rates
      of WAS protein (WASP)(-) and wild-type (WT) platelets were measured by injection
      of 5-chloromethylfluorescein diacetate (CMFDA)-labeled platelets into WT or WASP(
      ) recipients, and by in vivo biotinylation. Platelet and reticulated platelet
      counts were performed using quantitative flow cytometry. Bone marrow
      megakaryocyte number and ploidy was assessed by flow cytometry. Phagocytosis of
      CMFDA-labeled, opsonized platelets was assessed using bone marrow-derived
      macrophages. Serum antiplatelet antibodies were assayed via their binding to WT
      platelets. RESULTS: CMFDA-labeled WASP(-) platelets are consumed more rapidly
      than WT platelets in either WT or WASP(-) recipients. In vivo biotinylation
      studies corroborate these findings and show a normal consumption rate for WASP(-)
      reticulated platelets. The number of reticulated platelets is reduced in WASP(-)
      mice, but a significant number of the mice show an increased proportion of
      reticulated platelets and more severe thrombocytopenia. Sera from some of the
      latter group contain antiplatelet antibodies. Compared to WT platelets, WASP(-)
      platelets opsonized with anti-CD61 or 6A6 antibody are taken up more rapidly by
      bone marrow-derived macrophages. In vivo consumption rates of WASP(-) platelets
      are more accelerated by opsonization than are those of WT platelets. CONCLUSION:
      Both rapid clearance and impaired production contribute to the thrombocytopenia
      of murine WAS. Increased susceptibility of opsonized WASP(-) platelets to
      phagocytosis leads to increased in vivo clearance. This correlates with a higher
      incidence of individuals with an elevated fraction of reticulated platelets, a
      more severe thrombocytopenia, and antiplatelet antibodies.

PMID- 18346837
TI  - Deficiency of Src family kinases compromises the repopulating ability of
      hematopoietic stem cells.
AB  - OBJECTIVE: Src family kinases (SFK) have been implicated in regulating growth
      factor and integrin-induced proliferation, migration, and gene expression in
      multiple cell types. However, little is known about the role of these kinases in
      the growth, homing, and engraftment potential of hematopoietic stem and
      progenitor cells. RESULTS: Here we show that loss of hematopoietic-specific SFKs
      Hck, Fgr, and Lyn results in increased number of Sca-1(+)Lin(-) cells in the bone
      marrow, which respond differentially to cytokine-induced growth in vitro and
      manifest a significant defect in the long-term repopulating potential in vivo.
      Interestingly, a significant increase in expression of adhesion molecules, known
      to coincide with the homing potential of wild-type bone marrow cells is also
      observed on the surface of SFK(-/-) cells, although, this increase did not affect
      the homing potential of more primitive Lin(-)Sca-1(+) SFK(-/-) cells. The stem
      cell-repopulating defect observed in mice transplanted with SFK(-/-) bone marrow
      cells is due to the loss of Lyn Src kinase, because deficiency of Lyn, but not
      Hck or Fgr, recapitulated the long-term stem cell defect observed in mice
      transplanted with SFK(-/-) bone marrow cells. CONCLUSIONS: Taken together, our
      results demonstrate an essential role for Lyn kinase in positively regulating the
      long-term and multilineage engraftment of stem cells, which is distinct from its
      role in mature B cells and myeloid cells.

PMID- 18346838
TI  - Predictive factors for outcomes after reduced intensity conditioning
      hematopoietic stem cell transplantation for hematological malignancies: a 10-year
      retrospective analysis from the Societe Francaise de Greffe de Moelle et de
      Therapie Cellulaire.
AB  - This retrospective study analyzed the impact of demographic and transplantation
      variables on outcomes of 1108 patients who have undergone allogeneic
      hematopoietic stem cell transplantation after reduced intensity conditioning (RIC
      HSCT) for hematological malignancies and were reported to the Societe Francaise
      de Greffe de Moelle et de Therapie Cellulaire registry between November 1994 and
      December 2004. Only 442 patients (40%) were in complete remission (CR) at time of
      transplantation. Peripheral blood stem cells were used in the majority of
      patients (n = 878; 79%), 255 patients received fludarabine and low-dose total
      body irradiation, while 465 patients (42%) fludarabine and busulfan with rabbit
      anti-thymocyte globulins (ATG). The impact of demographic and transplant
      variables was studied on overall (OS) and event-free survival (EFS) in univariate
      and multivariate analysis. With a median follow-up of 21 months, 3-year
      probability of OS and EFS was 42% and 30%, respectively, and treatment-related
      mortality was 15% at 2 years. The multivariate analysis showed a significant
      negative impact on OS and EFS of the absence of CR status before transplantation;
      conditioning regimen, including >10 mg/kg ATG; and minor ABO incompatibility. In
      conclusion, this study highlights the major impact on RIC HSCT outcome of disease
      status before transplantation, ATG dose and ABO incompatibility.

PMID- 18346839
TI  - R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma
      cells.
AB  - OBJECTIVE: Bcl-2 family proteins play a critical role in malignancies by
      regulating the balance between cell survival and apoptosis. R-(-)-gossypol (AT
      101) is a small molecule that mimics the BH3 domain of cellular Bcl-2 inhibitors
      and interferes with the function of prosurvival Bcl-2 proteins. We examined the
      cytotoxicity of AT-101 in the context of multiple myeloma, a fatal hematological
      malignancy. MATERIALS AND METHODS: Multiple myeloma cell lines and primary cells
      obtained from multiple myeloma patients were used to investigate the effects of
      AT-101. Cell viability, apoptosis, and apoptosis pathways were examined using
      conventional viability assays, flow cytometry, and immunoblots. RESULTS: AT-101
      was not only cytotoxic to conventional multiple myeloma cell lines, but was also
      effective against drug-resistant cell lines and primary multiple myeloma patient
      cells. Furthermore, AT-101 decreased proliferation of multiple myeloma cell lines
      in the presence of marrow stromal cells, indicating that this drug may overcome
      the protective effect of the microenvironment that is important for multiple
      myeloma cell proliferation and survival. Apoptosis was activated via the
      mitochondrial pathway in multiple myeloma cell lines treated with AT-101 as
      demonstrated by an increased Bax to Bcl-2 ratio, mitochondrial membrane
      depolarization, and caspase activation. Finally, our studies demonstrated that AT
      101 exhibits potent synergy with dexamethasone, a valuable therapeutic for
      multiple myeloma. CONCLUSION: These data suggest that the activity of AT-101 may
      be highly relevant to multiple myeloma disease biology and may represent an
      option for treatment of patients with this disease.

PMID- 18346840
TI  - Regulation of human B lymphopoiesis by the transforming growth factor-beta
      superfamily in a newly established coculture system using human mesenchymal stem
      cells as a supportive microenvironment.
AB  - OBJECTIVES: To characterize and evaluate the validity of a novel coculture system
      for studying human B-lymphocyte developmental biology. MATERIALS AND METHODS: We
      developed a long-term culture system to produce B lymphocytes from human CD34(+)
      cells purified from umbilical cord blood using human mesenchymal stem cells
      (hMSC) as stroma. We evaluated the effects of several low molecular weight
      inhibitors, recombinant proteins, and neutralizing antibodies (Abs) as potential
      regulators of B-lymphocyte development. RESULTS: Our cocultures of 2000 CD34(+)
      cells in the presence of stem cell factor and Flt3-ligand produced 1-5 x 10(5)
      CD10(+) cells after 4 weeks of culture. Surface IgM(+) immature B cells began to
      appear after 4 weeks. We evaluated the negative-regulatory effects of the
      transforming growth factor (TGF)-beta superfamily on human B lymphopoiesis, and
      found that adding an anti-activin A antibody enhanced generation of CD10(+) cells
      two- to three-fold. As well, the proportion of CD10(+) cells in the generated
      cells increased markedly, indicating that activin A downregulated B lymphopoiesis
      more efficiently than myelopoiesis. Addition of TGF-beta1 suppressed B-lymphocyte
      production by 20% to 30%, while addition of an anti-bone morphogenetic protein
      (BMP)-4 antibody or recombinant BMP-4 had no effect. Therefore, the strength of
      ability to suppress human B lymphopoiesis seemed to be activin A > TGF-beta1 >
      BMP-4. None of these three factors influenced the emergence of IgM(+) cells.
      CONCLUSIONS: hMSC coculture supported human B lymphopoiesis. Activin A
      selectively suppressed B lymphocyte production.

PMID- 18346841
TI  - G-CSF treatment after myocardial infarction: impact on bone marrow-derived vs
      cardiac progenitor cells.
AB  - OBJECTIVE: Besides its classical function in the field of autologous and
      allogenic stem cell transplantation, granulocyte colony-stimulating factor (G
      CSF) was shown to have protective effects after myocardial infarction (MI) by
      mobilization of bone marrow-derived progenitor cells (BMCs) and in addition by
      activation of multiple signaling pathways. In the present study, we focused on
      the impact of G-CSF on migration of BMCs and the impact on resident cardiac cells
      after MI. MATERIALS AND METHODS: Mice (C57BL/6J) were sublethally irradiated, and
      BM from green fluorescent protein (GFP)-transgenic mice was transplanted.
      Coronary artery ligation was performed 10 weeks later. G-CSF (100 microg/kg) was
      daily injected for 6 days. Subpopulations of enhanced GFP(+) cells in peripheral
      blood, bone marrow, and heart were characterized by flow cytometry. Growth factor
      expression in the heart was analyzed by quantitative real-time polymerase chain
      reaction. Perfusion was investigated in vivo by gated single photon emission
      computed tomography (SPECT). RESULTS: G-CSF-treated animals revealed a reduced
      migration of c-kit(+) and CXCR-4(+) BMCs associated with decreased expression
      levels of the corresponding growth factors, namely stem cell factor and stromal
      derived factor-1 alpha in ischemic myocardium. In contrast, the number of
      resident cardiac Sca-1(+) cells was significantly increased. However, SPECT
      perfusion showed no differences in infarct size between G-CSF-treated and control
      animals 6 days after MI. CONCLUSION: Our study shows that G-CSF treatment after
      MI reduces migration capacity of BMCs into ischemic tissue, but increases the
      number of resident cardiac cells. To optimize homing capacity a combination of G
      CSF with other agents may optimize cytokine therapy after MI.

PMID- 18346842
TI  - Delineation and functional status monitoring in small saline wetlands of NE
      Spain.
AB  - The small playa-lakes and other saline wetlands of Monegros, scattered over a dry
      area with winter cereal monoculture, are threatened by the settlement of new
      irrigation districts and other kinds of human pressure. Enforcing the protection
      rules of European Union in these valuable habitats requires, first, their
      delimitation and monitoring. This article shows how these tasks can be undertaken
      using remote sensing in conjunction with field observations. A series of Landsat
      images covering different seasons provided a comprehensive view of these wetlands
      encompassing their changing facies, hydrologic regime, state of conservation, and
      functional status. Remotely-sensed data were the primary, and in most cases the
      only available, source of consistent information. Our approach can help planning
      and surveying for the implementation of saline wetland protection measures in
      harmony with the conterminous agricultural areas.

PMID- 18346843
TI  - Kaempferol and quercetin stimulate granulocyte-macrophage colony-stimulating
      factor secretion in human prostate cancer cells.
AB  - Granulocyte-macrophage colony-stimulating factor (GM-CSF) holds immunotherapeutic
      promise in prostate cancer as it activates the host immune system. Increased
      production of GM-CSF by cancer cells may facilitate host immunosurveillence by
      the dendritic cells (DC). Here, we studied the effects of kaempferol (K) and
      quercetin (Q) on the production of GM-CSF in PC-3 cells. Human cytokine antibody
      array revealed that treatment with K or Q increased GM-CSF release by PC-3 cells.
      We further observed by ELISA that K and Q in a concentration-dependent manner
      increased GM-CSF production without affecting its mRNA levels. Inhibitors of
      vesicular traffic through the endoplasmic reticulum and Golgi-blocked GM-CSF
      secretory stimulation. A microtubule-stabilizing agent stimulated GM-CSF release,
      whereas tubulin and actin depolymerizers suppressed K- or Q-stimulated secretion
      of GM-CSF. Depletion of extracellular or intracellular calcium ion inhibited the
      GM-CSF secretion upregulated by both K and Q. Furthermore, we showed that K- and
      Q-stimulated GM-CSF production involves PLC, PKC, and MEK1/2 activation. Treating
      human DC with the conditioned medium of K- or Q-incubated PC-3 cells increased
      chemotaxis of DC, which was significantly attenuated when the conditioned medium
      was incubated with the neutralizing antibody against GM-CSF. Taken together, our
      results demonstrate that K and Q activate an immune response in the prostate
      cancer cells by stimulating GM-CSF production, which in turn could result in the
      recruitment of DCs to the tumor site.

PMID- 18346844
TI  - MEK inhibitor enhances the inhibitory effect of imatinib on pancreatic cancer
      cell growth.
AB  - Imatinib mesylate (imatinib) inhibits the c-Kit-dependent tyrosine kinase
      activities and highly effective in the treatment of CML and GIST patients.
      Although pancreatic cancer is reported to express c-Kit, imatinib does not
      effectively inhibit pancreatic cancer cell growth at physiological
      concentrations. Therefore, we investigated the mechanism of resistance of
      pancreatic cancer to imatinib treatment. Imatinib inhibited growth of pancreatic
      cancer cell lines in concentration and time-dependent fashion regardless of c-Kit
      expression. However, 5 microM imatinib, which is almost a mean maximal plasma
      concentration in clinical setting, failed to suppress pancreatic cancer cell
      growth. Western blot analysis demonstrated that 5 microM imatinib treatment for
      1h activated the MEK-MAPK pathway and the activation was independent of Ras
      activation. Administration of 5 microM imatinib and 1 microM U0126 (MEK
      inhibitor) significantly suppressed pancreatic cell growth. Our results indicate
      that a combination therapy of imatinib and MEK inhibitor can be a new therapeutic
      strategy to suppress the progression of pancreatic cancer.

PMID- 18346845
TI  - Regulation of the nitric oxide pathway genes by tetrahydrofurandiols: microarray
      analysis of MCF-7 human breast cancer cells.
AB  - THF-diols (9,12-oxy-10,13-dihydroxyoctadecanoic and 10,13-oxy-9,12
      dihydroxyoctadecanoic acids) are endocrine disrupters in rats and mitogens in
      breast cancer cells. Microarray analyses and real-time PCR analyses on RNA from
      THF-treated MCF-7 cells revealed a number of genes (caveolin 1, heat shock
      protein 90 alpha and 90 beta, vascular endothelial growth factor, ATPase, Ca++
      transporting, ubiquitous) in the nitric oxide pathway (NOP) were targets for THF
      diols. Chromatin immunoprecipitation studies suggest THF-diols modify of histone
      H4 acetylation at the caveolin 1 promoter via an epigenetic mechanism. These
      findings are consistent with the well-known involvement of NOP genes in cell
      proliferation and sexual behavior.

PMID- 18346846
TI  - Electrostatic separation for multi-size granule of crushed printed circuit board
      waste using two-roll separator.
AB  - The electrostatic separation is an effective method for recycle of crushed waste
      electrical and electronic equipment (WEEE). However, the robustness of the
      classical roll-type separator is vulnerable because of its sensitivity to
      variation of granule size. A new "two-roll type corona-electrostatic separator"
      was built to overcome the limitation of the classical one considering the actual
      situation of the industrial application which always contains granule with
      different size. Multi-size granule of crushed printed circuit board (PCB) wastes
      was used for investigation and the results showed that the efficiency of the
      separation process was improved by using the new separator. Compared with the
      process (lower voltage) performed on the old separator, the metal products
      increased 34% while the middling products reduced 73%, respectively. Compared
      with the process (higher voltage) performed on the old separator, the metal
      products increased 22% while the middling products reduced 59%, respectively. In
      addition, the metal component of the middling products using new machine notably
      decreased, 33% (new machine) compared with 58% (lower voltage) and 66% (higher
      voltage). The efficiency of the separation process is enhanced compared with the
      classical one.

PMID- 18346847
TI  - Removal of Cr(VI) and Ni(II) from aqueous solution by fused yeast: study of
      cations release and biosorption mechanism.
AB  - Biosorption of Cr(VI) and Ni(II) by a fused yeast from Candida tropicalis and
      Candida lipolytica under varying range of pH, initial metal concentration and
      reaction time was investigated. Net cation release and Cr removal reached 2.000
      mmol/l and 81.37% when treating 20mg/l Cr(VI) at pH 2 with 25mg/l biomass for 30
      min, while for Ni were 0.351 mmol/l and 64.60%, respectively. Trace metal
      elements such as Co, Cu, Mn, Mo, Se and Zn played active role in biosorption as
      important ingredients of functional enzymes. Cr(VI) was reduced to less toxic
      Cr(III) and chelated with extracellular secretions, and further accumulated
      inside the cells. For Ni biosorption, however, largely a passive uptake process
      influenced by ion gradient led to lower adsorption capacity and cations release.
      Fourier transform infrared (FTIR) spectrum analysis indicated that amide and
      pyridine on cells were involved in binding with Cr, but for Ni, bound-OH and
      nitro-compounds were the main related functional groups. Scanning electron
      microscopy (SEM) and atomic force microscopy (AFM) analysis confirmed that
      considerable amounts of metals precipitated on cell surface when dealing with
      high concentration metals.

PMID- 18346848
TI  - A novel slurry sampling analysis of lead in different water samples by
      electrothermal atomic absorption spectrometry after coprecipitated with
      cobalt/pyrrolidine dithiocarbamate complex.
AB  - A preconcentration/separation technique based on the coprecipitation of lead with
      cobalt/pyrrolidine dithiocarbamate complex (Co(PDC)(2)) and subsequently its
      direct slurry sampling determination by electrothermal atomic absorption
      spectrometry (AAS) was described. For this purpose, at first, lead was
      coprecipitated with cobalt/pyrrolidine dithiocarbamate complex formed using
      ammonium pyrrolidine dithiocarbamate (APDC) as a chelating agent and cobalt as a
      carrier element. The supernatant was then separated and the slurry of the
      precipitate prepared in Triton X-100 was directly analyzed by electrothermal
      atomic absorption spectrometry with respect to lead concentration. The effects of
      experimental conditions on coprecipitation of lead with gathering precipitate as
      well as homogeneity and stability of the slurry were investigated. After the
      optimization of experimental parameters, a 100-fold enrichment of the analyte
      with quantitative recovery (>90%) and high precision (<10% R.S.D.) were obtained.
      By using the proposed technique, the lead concentrations in heavy matrices of
      Certified Sea-water and wastewater samples could be practically and rapidly
      determined in the range of 95% confidence level. The detection limit of the
      described method for lead using sample-matching blanks was 1.5 ng/L (3 sigma,
      N=10).

PMID- 18346849
TI  - Prefrontal modulation of tactile responses in the ventrobasal thalamus of rats.
AB  - Prefrontal cortex (PFC) has been implicated in modulation of sensory information
      processing in somatosensory cortex. However, it remains unclear whether or not
      PFC regulates sensory information in thalamus. In the present study, the effect
      of PFC stimulation on tactile responses of neurons in the ventrobasal thalamus
      (VB) of the rat was investigated by single-unit recording. PFC stimulation
      significantly enhanced the signal-noise ratio (tactile responses/background
      activities) in 16 out of 66 VB neurons (24.2%) that had receptive fields in fore
      or hind limbs. Such changes can be classified into three different categories:
      (1) PFC stimulation not only increased the tactile responses, but also suppressed
      the background activities of neurons (six neurons, 9.1%); (2) PFC stimulation
      only increased the tactile responses of neurons (five neurons, 7.6%); (3) PFC
      stimulation only suppressed the background activities of neurons (five neurons,
      7.6%). Our results suggest that PFC also modulates somatosensory information at
      the thalamic level.

PMID- 18346850
TI  - Memantine increases brain production of kynurenic acid via protein kinase A
      dependent mechanism.
AB  - We describe a novel aspect of action of memantine ex vivo, in the brain cortical
      slices and in vitro, in mixed glial cultures. The drug potently increased the
      production of kynurenic acid, an endogenous tryptophan metabolite blocking N
      methyl-D-aspartate (NMDA) and nicotinic alpha7 receptors. In cortical slices
      memantine, an open-channel NMDA blocker (100-150 microM), but not the competitive
      NMDA receptor antagonist, LY235959 increased the production of kynurenic acid.
      Neither SCH23390, D1 receptor antagonist (50 microM) nor raclopride, D2 receptor
      antagonist (10 microM) changed the memantine-induced effects. Propranolol (100
      microM) has partially reduced its action. Selective cAMP-dependent protein kinase
      (PKA) inhibitor, KT5720 (1 microM), but not selective protein kinase C (PKC)
      inhibitor, NPC15437 (30 microM) totally reversed the action of memantine. In
      mixed glial cultures, 2-24 h incubation with memantine (2-50 microM) enhanced the
      production of kynurenic acid. Memantine (up to 0.5 mM) has not affected the
      activity of kynurenic acid biosynthetic enzymes. The obtained data suggest that
      memantine enhances the production of kynurenic acid in PKA-mediated way. This
      effect may partially contribute to the therapeutic actions of memantine and be of
      a potential clinical importance.

PMID- 18346851
TI  - AlphaII-spectrin breakdown product increases in principal cells in the gerbil
      main olfactory bulb following transient ischemia.
AB  - In pathological states, calpains in neurons easily degrade spectrin and yield
      specific fragments called spectrin breakdown products characterized by their high
      stabilities both in vitro and in vivo. In the present study, we investigated
      chronological changes in alphaII-spectrin immunoreactivity and protein levels
      using the antibody to detect both the naive form and breakdown products of
      alphaII-spectrin in the gerbil main olfactory bulb (MOB) after 5 min of transient
      forebrain ischemia. In sham-operated gerbils, weak alphaII-spectrin
      immunoreactivity was detected in principal (mitral and tufted) cells. Ten days
      after ischemia/reperfusion, alphaII-spectrin immunoreactivity was increased in
      principal cells. Fifteen days after ischemia/reperfusion, alphaII-spectrin
      immunoreactivity in the somata and processes of principal cells was markedly
      increased. Thereafter, alphaII-spectrin immunoreactivity in the principal cells
      in the ischemic MOB was decreased with time. In Western blot study, spectrin
      protein bands were detected in naive form (230 kDa) and its breakdown product
      (150 kDa). The breakdown product in MOB homogenates were significantly increased
      15 days after ischemia/reperfusion and thereafter decreased with time after
      ischemia/reperfusion. Our results indicate that alphaII-spectrin breakdown
      product in the gerbil MOB is changed in principal cells after ischemic insult.

PMID- 18346852
TI  - Protein expression profile in the amygdala of rats with methamphetamine-induced
      behavioral sensitization.
AB  - Repeated exposure to methamphetamine (MAP) results in a progressively enhanced
      and enduring behavioral response to the drug. This phenomenon is known as
      behavioral sensitization. MAP-induced sensitization has been suggested to
      underlie certain aspects of MAP psychosis and schizophrenia. The mesolimbic
      dopamine system including the ventral tegmental area, nucleus accumbens (NAc) and
      associated brain regions such as the amygdala (AMG) are proposed to be involved
      in the behavioral sensitization. However, the molecular mechanisms underlying
      this protracted alteration of behavior are almost unknown. Here we examined
      protein expression profiles in the AMG of acute MAP-treated and MAP-sensitized
      rats using 2-DE-based proteomics. Analysis revealed that 64 and 43 protein spots
      were differentially regulated in the AMG of acute MAP-treated and MAP-sensitized
      rats, respectively, when compared to control rats. A total of 48 and 34 proteins
      were identified in these two models, respectively using MALDI-ToF-MS. When the
      results were compared between acute and chronic MAP-treated groups, only 9
      proteins were identified in common. These proteins could be related to acute MAP
      effects and/or non-specific effects. It is therefore suggested that AMG react
      differently to the acute and repeated administration of MAP at least at the
      protein expression level. A number of proteins in the categories of synaptic,
      cytoskeletal, oxidative stress, apoptosis, and mitochondria related proteins were
      differentially expressed in the AMG of sensitized animals. Changes of these
      protein expressions in the AMG could be associated with the mechanism underlying
      behavioral sensitization.

PMID- 18346853
TI  - Epidemiological survey of cestode-larva disease in Greek sheep flocks.
AB  - The epidemiological status of hydatidosis, cysticercosis, and gid in sheep and
      the production practices of sheep farmers that increase the risk of exposure of
      sheep to infecting agents of these diseases were investigated in Thessaly,
      central Greece during 2002-2006. A total of 700 hoggets (sheep up to the age of 1
      year) and 1500 adult sheep were examined randomly at an abattoir survey and the
      prevalences of hydatidosis and cysticercosis were found 39.32% and 29.41%,
      respectively. Hoggets had significantly lower prevalences of hydatidosis and
      cysticercosis compared to adult sheep (p<0.001). The distribution of parasitic
      cysts showed an overdispersion pattern mostly in the hogget population. The
      proportion of fertile hydatid cysts was significantly higher in hoggets compared
      to adult sheep (p<0.001). A cohort of 74 sheep flocks was observed during the
      same period in a prospective survey to assess the incidence of gid. A total of 57
      sheep belonging to 15 flocks (20.27% of investigated flocks) developed clinical
      signs of gid at an annual rate of 11.40+/-4.77 (95% C.I.). In the infected flocks
      there were 3.80+/-0.92 (95% C.I.) gid cases per flock. The mean age of onset of
      clinical signs for all sheep was 11.86+/-1.33 months (95% C.I.) (range 5-22
      months) while for hoggets was 8.48+/-0.73 (95% C.I.) (range 5-12 months) and for
      adult sheep 17.23+/-1.42 (95% C.I.) (range 13-22 months). A significant
      difference was observed in the prevalence of unilateral blindness between hoggets
      (31.42%) and adult sheep (4.54%) (p<0.05). The most common production practices
      identified in a questionnaire survey of sheep farmers that may increase the risk
      of exposure of sheep to hydatidosis, cysticercosis, and gid were the improper
      disposal of dead animals, the access of farm dogs to offal of slaughtered sheep,
      the carelessness of farmers to treat farm dogs with anthelmintics, and the
      grazing of flocks in fields where stray dogs have free access.

PMID- 18346854
TI  - Prevalence and molecular characterization of bovine Cryptosporidium isolates in
      India.
AB  - A survey based on PCR assay of 18S SSU rRNA gene revealed a 30.2% infection with
      Cryptosporidium spp., out of 457 faecal samples collected from neonatal bovine
      calves across three different regions of India. The PCR-RFLP pattern of the gene
      in all the positive cases established the species as Cryptosporidium parvum.
      Highest prevalence was recorded in the monsoon months (37.3%) and in the calves
      showing acute diarrhoea (32.3%). The calves below 15 days of age were mostly
      affected (45.1%). The infection was more prevalent in the northern parts (35.4%)
      of the country than in the eastern or southern parts. Results indicated that C.
      parvum was the only species of Cryptosporidium prevalent in bovine calves in
      three different geographical regions of India.

PMID- 18346855
TI  - Effects of reinforcer quality and step size on rats' performance under
      progressive ratio schedules.
AB  - The Mathematical Principles of Reinforcement (MPR) model accurately predicts
      performance in fixed ratio (FR) schedules of reinforcement. The aim of the
      present study was to assess the generality of MPR with rats responding under
      progressive ratio (PR) schedules of different step sizes (PR1 or PR3) that
      provided either food or saccharin pellets. The results showed that the rats
      responding for saccharin pellets produced higher breakpoints (i.e., completed
      higher ratios) than those responding for food pellets. In terms of theoretical
      parameters, one finding unanticipated on the basis of MPR was that the a
      parameter (specific activation) was higher for the PR3 schedules. This finding
      suggests that specific activation may be affected indirectly by motor parameters
      of the task.

PMID- 18346856
TI  - Neonatal extra-corporeal life support: indications and limitations.
AB  - Cardiac extra-corporeal life support is used more frequently in the current era
      of complex, high-risk neonatal heart surgery. Although outcome for neonates with
      complex heart disease has improved in the last decade, thanks to advances in
      surgery and intensive care, survival in the subset that require extra-corporeal
      support remains unchanged at below 40%. Neonatal cardiac extra-corporeal support
      is a technically challenging therapy that is applied in a range of contexts
      including: post-operative low cardiac output syndrome, cardiac arrest, high-risk
      interventional catheterisation or as a bridge to recovery from dysrhythmia and
      myocarditis. Extra-corporeal life support has increased in particular for
      neonates with single ventricle disease in the last 5 years, mainly achieving
      similar results to biventricular patients. Further research is required in order
      to determine the optimal methods for patient selection and to establish important
      predictors of outcome including the longterm neurological development of
      survivors.

PMID- 18346857
TI  - Exogenous leptin promotes the recovery of regressed ovary in fasted ducks.
AB  - The present study was undertaken to examine the effect of administered
      recombinant mouse leptin on the recovery of regressed ovary in fasted ducks.
      Twenty-eight ducks were divided into five groups: fed ad libitum (control; n=5),
      fasted control (FC; n=5), fasted+low dose of leptin (F+L; n=5), fasted+medium
      dose of leptin (F+M; n=5) and fasted+high dose of leptin (F+H; n=3). All four
      fasted groups were fasted for 2 days and then ad libitum and the ducks were
      treated with leptin at doses of 0 (control and FC), 50 (F+L), 250 (F+M) and 1000
      (F+H) microg/kg body weight/day on day 3-5. Results showed that a moderate dose
      of leptin (250 microg/kg body weight/day) injected during the re-feeding period:
      (i) promoted the recovery of the regressed ovary as evidenced by an increase in
      ovary weight and recovery of yellow hierarchical follicles; (ii) elevated the
      plasma 17beta-estradiol (E(2)) level; (iii) increased the mRNA levels of ovary
      follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR)
      and estrogen receptor-beta (ER-beta). Furthermore, the results also showed that a
      high dose of leptin (1000 microg/kg body weight/day) may have a negative effect
      on the recovery of the regressed ovary. In conclusion, this study indicates that,
      in ducks, leptin may be involved in the recovery of the regressed ovary caused by
      2 days of fasting. This effect may be related to increased plasma E(2) levels and
      stimulation of the mRNA levels of ovarian FSHR, LHR and especially ER-beta.

PMID- 18346858
TI  - Protective effects of Terminalia arjuna against Doxorubicin-induced
      cardiotoxicity.
AB  - Terminalia arjuna has been marked as a potential cardioprotective agent since
      vedic period. The present study was aimed to investigate the effects of butanolic
      fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced
      cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05
      was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85
      mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks.
      Thereafter, all the animals except saline and TA-05-treated controls were
      administered 20 mg/kg Dox intraperitonially. There was a significant decrease in
      myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in
      animals treated with Dox. Concurrently marked increase in serum creatine kinase
      MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation
      (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase
      in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction
      in lipid peroxidation as compared to Dox-treated animals. Electron microscopic
      studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray,
      focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions,
      whereas the concurrent administration of TA-05 led to a lesser degree of Dox
      induced histological alterations. These findings suggest that butanolic fraction
      of Terminalia arjuna bark has protective effects against Dox-induced
      cardiotoxicity and may have potential as a cardioprotective agent.

PMID- 18346859
TI  - Baccharis trimera: effect on hematological and biochemical parameters and
      hepatorenal evaluation in pregnant rats.
AB  - AIM OF THE STUDY: This investigation evaluated the effect of a hydroethanolic
      extract of Baccharis trimera on pregnant Wistar rats, once the plant is well
      known consumed in pregnancy and little is known on its potentially toxic effects
      on pregnant women. MATERIAL AND METHODS: Thirty-five female rats were distributed
      into three groups. Those in treatments 1 and 2 were given 8.4 mg/kg of the
      extract orally from gestational day (GD) 1 to 19 and from GD 6 to 15,
      respectively, whereas those in the control group received distilled water orally
      from GD 1 to 19. Body weights were recorded on GD 1, 6, 15, and 20. On GD 20
      animals were anesthetized, blood samples were collected and maternal livers,
      kidneys, and spleens were weighed and processed for histological studies.
      RESULTS: No clinical signs of maternal toxicity and no changes in hematological
      parameters were observed. Urea levels and kidney weights differed significantly
      between animals receiving treatment 1 and controls. Histopathological alterations
      were found in kidneys and livers in both treatment groups. CONCLUSIONS: The
      hydroethanolic extract of Baccharis trimera administered to pregnant rats at 8.4
      mg/kg was toxic to maternal kidney and liver cells, although such alterations are
      reversible once administration is discontinued.

PMID- 18346860
TI  - Circadian gene expression in the murine larynx.
AB  - OBJECTIVE: Symptoms of airway diseases are often associated with specific times
      of the day. For example, midnight worsening of cough is a frequent complaint of
      patients with laryngitis and bronchitis. We speculate that these symptoms are
      under the control of the circadian clock, and the clock genes in the airway
      epithelium play some important roles. In the present study, we tried to prove the
      time specific expressions of clock oscillating genes in the murine larynx.
      MATERIALS AND METHODS: Adult wild-type C57/Bl6 mice and mCry1(-/-)mCry2(-/-)
      mutant mice were used for this study. We employed immunohistochemistry and/or
      Northern blotting for examining the circadian expression of mPer1, mPer2,
      C/EBPbeta, HNF3beta, and MUC5b. RESULTS: The expression of mPer2 mRNA showed a
      strong day-night expression difference, which was abolished after the lesion of
      the suprachiasmatic nucleus, and in mCry1(-/-)mCry2(-/-) mutant mice. mPER1 and
      mPER2 proteins both showed very similar expression profiles in the epithelium and
      submucosal glands with a peak in the evening and a trough in the early morning.
      Other nuclear proteins such as C/EBPbeta and HNF3beta did not show the rhythms.
      MUC5b protein showed circadian oscillation in the laryngeal submucosal gland.
      CONCLUSION: In this study, we confirmed the existence of a local laryngeal clock
      which is controlled by the central clock in the suprachiasmatic nucleus. MUC5b
      protein in the submucosal mucous gland also showed circadian rhythm. We consider
      that these rhythmic expressions may cause the time specific symptoms among
      laryngeal diseases.

PMID- 18346861
TI  - Provider and patient intervention to improve weight loss: a pilot study in a
      public hospital clinic.
AB  - OBJECTIVE: To assess the efficacy of a literacy-appropriate weight loss
      intervention targeting providers and patients in improving physicians' weight
      loss counseling and patients' self-reported beliefs, and self-efficacy. METHODS:
      The study took place in a public hospital nephrology clinic. The intervention
      included two physician workshops and a small group patient education. Physician
      patient communication was observed and coded. Structured interviews assessed
      patient recall of weight loss recommendations, weight-related beliefs, and self
      efficacy. RESULTS: 64 patient visits were observed before and after the
      intervention. 75% of patients were African American, 96% lacked private
      insurance, 71% had low literacy skills; mean body mass index (BMI) of 35 kg/m(2).
      Physician counseling improved significantly post-intervention, particularly in
      assessing, supporting and advising patients about weight loss and exercise.
      Patients reported increases in recall of weight loss recommendations and were
      more likely to report greater confidence about losing weight (52% vs. 70%,
      p<0.01). CONCLUSIONS: This pilot study offers promising directions to address
      provider and patient barriers to weight loss education and counseling in a public
      hospital. PRACTICE IMPLICATIONS: Hospital-based weight loss interventions need to
      target both physicians and patients.

PMID- 18346862
TI  - Interspecies differences in acetaminophen sensitivity of human, rat, and mouse
      primary hepatocytes.
AB  - Most of the experiments studying acetaminophen (APAP) induced hepatotoxicity were
      performed using moue as model specie, right because its high sensitivity. While
      the toxic responses can be called forth easily in mice, the human relevancy of
      these results is questionable. In this study human, rat, and mouse primary
      hepatocytes were treated with increasing concentrations of APAP, and cell
      viability was measured by MTT cytotoxicity assay. Pronounced interspecies
      differences were obtained in cell viability following 24h of APAP treatment
      starting at 24h after seeding (EC50: 3.8mM, 7.6mM, and 28.2mM, in mouse, rat, and
      human hepatocyte culture, respectively). The longer time of culturing highly
      increased the resistance of hepatocytes of all species investigated. In rat
      hepatocyte culture EC50 values were 6.0mM, 12.5mM, and 18.8mM, when starting APAP
      treatment after 24, 48, and 72 h of seeding. Although N-acetylbenzoquinoneimine,
      a minor metabolite of APAP, which is mainly formed by CYP2E1 at high APAP
      concentration in every species studied, is thought to initiate the toxic
      processes, no correlation was found between CYP2E1 activities and hepatocyte
      sensitivity of different species. We conclude that the toxicity induced by APAP
      overdose highly depends on the animal model applied.

PMID- 18346863
TI  - Peroxide-induced cell death and lipid peroxidation in C6 glioma cells.
AB  - Peroxides are often used as models to induce oxidative damage in cells in vitro.
      The aim of the present study was to elucidate the role of lipid peroxidation in
      peroxide-induced cell death. To this end (i) the ability to induce lipid
      peroxidation in C6 rat astroglioma cells of hydrogen peroxide (H2O2), cumene
      hydroperoxide (CHP) and t-butyl hydroperoxide (t-BuOOH) (ii) the relation between
      peroxide-induced lipid peroxidation and cell death in terms of time and
      concentration dependency and (iii) the capability of the lipid peroxidation chain
      breaking alpha-tocopherol to prevent peroxide-induced lipid peroxidation and/or
      cell death were investigated. Lipid peroxidation was characterised by measuring
      thiobarbituric acid reactive substances (TBARS) and, by HPLC, malondialdehyde
      (MDA), 4-hydroxynonenal (4-HNE) and hexanal. Within 2 h CHP, t-BuOOH and H2O2
      induced cell death with EC50 values of 59+/-9 microM, 290+/-30 microM and 12+/
      1.1 mM, respectively. CHP and t-BuOOH, but not H2O2 induced lipid peroxidation in
      C6 cells with EC50 values of 15+/-14 microM and 130+/-33 microM, respectively.
      The TBARS measured almost exclusively consisted of MDA. 4-HNE was mostly not
      detectable. The concentration of hexanal slightly increased with increasing
      concentrations of organic peroxides. Regarding time and concentration dependency
      lipid peroxidation preceded cell death. Pretreatment with alpha-tocopherol (10
      microM, 24 h) prevented both, peroxide-induced lipid peroxidation and cell death.
      The results strongly indicate a major role of lipid peroxidation in the killing
      of C6 cells by organic peroxides but also that lipid peroxidation is not involved
      in H2O2 induced cell death.

PMID- 18346864
TI  - Type C coping, alexithymia, and heart rate reactivity are associated
      independently and differentially with specific immune mechanisms linked to HIV
      progression.
AB  - The maladaptive Type C coping style has been linked to disease progression in HIV
      and other immunologically mediated disorders. We hypothesized that strong Type C
      coping, higher levels of alexithymia, and greater cardiovascular (particularly
      heart rate) responses to, and prolonged recovery from stress would be associated
      with poorer functioning of immune parameters previously linked to HIV
      pathogenesis and progression: (1) antigen-stimulated production of the beta
      (beta)-chemokines MIP-1 alpha and MIP-1 beta, which bind to the HIV co-receptor
      CCR5 and block HIV entry into CD4(+) lymphocytes; and (2) antigen-stimulated
      production of the proinflammatory cytokine interleukin-6 (IL-6), which synergizes
      immune activation associated with HIV replication. We examined relations among
      psychological, cardiovascular, and immune variables in a baseline sample of 200
      HIV-infected, predominantly African American outpatients attending an HIV primary
      care clinic in inner-city Baltimore. In regression analyses adjusted for CD4(+)
      count and age, strong Type C coping was associated with significantly higher IL-6
      production, as predicted. The theoretically related construct of alexithymia was
      correlated with significantly lower stimulated production of HIV-inhibiting MIP-1
      alpha. Independent of alexithymia, greater heart rate reactivity, and poorer
      heart rate recovery in response to experimental stressors were also significantly
      associated with lower production of MIP-1 alpha, adjusted for cardiovascular
      medications, methadone use, CD4(+) count, and age. These findings support our
      primary set of hypotheses that maladaptive Type C coping, alexithymia, and heart
      rate reactivity/recovery are associated with disturbances in two key immune
      parameters implicated in HIV pathogenesis. Our secondary hypothesis, that
      dysregulated heart rate reactivity may mediate the connections between Type C
      coping and/or alexithymia and IL-6/ MIP-1 alpha was not confirmed. The finding
      that Type C coping, alexithymia, and heart rate reactivity/recovery are
      associated independently and differentially with specific aspects of relevant
      immune functioning may reflect distinct biobehavioral pathways that contribute to
      HIV progression.

PMID- 18346865
TI  - Preliminary evaluation of noninvasive microscopic imaging techniques for the
      study of vocal fold development.
AB  - Understanding pediatric voice development and laryngeal pathology is predicated
      on a detailed knowledge of the microanatomy of the layered structure of the vocal
      fold. Our current knowledge of this microanatomy and its temporal evolution is
      limited by the lack of pediatric specimen availability. By providing the
      capability to image pediatric vocal folds in vivo, a noninvasive microscopy
      technique could greatly expand the existing database of pediatric laryngeal
      microanatomy and could furthermore make longitudinal studies possible. A variety
      of natural-contrast optical imaging technologies, including optical frequency
      domain imaging (OFDI), full-field optical coherence microscopy (FF-OCM), and
      spectrally encoded confocal microscopy (SECM) have been recently developed for
      noninvasive diagnosis in adult patients. In this paper, we demonstrate the
      potential of these three techniques for laryngeal investigation by obtaining
      images of excised porcine vocal fold samples. In our study, OFDI allowed
      visualization of the vocal fold architecture deep within the tissue, from the
      superficial mucosa to the vocalis muscle. The micron-level resolution of SECM
      allowed investigation of cells and extracellular matrix fibrils from the
      superficial mucosa to the intermediate layer of the lamina propria (LP) (350
      microm penetration depth). The large field of view (up to 700 microm),
      penetration depth (up to 500 microm), and resolution (2x2x1microm [XxYxZ]) of FF
      OCM enabled comprehensive three-dimensional evaluation of the layered structure
      of the LP. Our results suggest that these techniques provide important and
      complementary cellular and structural information, which may be useful for
      investigating pediatric vocal fold maturation in vivo.

PMID- 18346866
TI  - Follow-up Contemporary Commercial Music (CCM) Survey: who's teaching what in
      nonclassical music.
AB  - A previous study, published in the Journal of Voice in 2003, revealed that a
      majority of teachers of Music Theater (MT), a style of Contemporary Commercial
      Music (CCM), had little professional experience and little formal training in
      vocal pedagogy for this style. Those who did indicate that they had had training
      did not describe the training nor quantify it in any manner. To ascertain what
      type of training was available for CCM in general and MT, in particular, a follow
      up study seemed warranted. A new questionnaire was developed which asked for
      further information from teachers of MT in several areas including performance
      experience, training methods, teaching philosophy, the use of terminology,
      knowledge of voice science and medicine, and other parameters. Responses were
      gathered from 145 singing teachers throughout the United States and several
      foreign countries. Statistical analysis obtained from the data may lead to both a
      better understanding of the kind of training available for teachers of CCM
      repertoire, and of its content and applicability.

PMID- 18346867
TI  - Consequences from emotional stimulus on breathing for singing.
AB  - This study aimed to investigate the effect from emotional stimulus on the
      correlation between intercostal (INT)/abdominal (rectus abdominis [RC], lateral
      abdomen [OBL], and lower lateral abdomen [LOBL]) muscle activity and trunk wall
      (upper thorax [UTX], lower thorax [LTX], and abdomen [ABD]) movement. An
      electromyographic (EMG) activity was recorded from the INT, RC, OBL, and LOBL
      sites. UTX, LTX, and ABD movement were traced with three strain gauge sensors.
      Recordings were compared between singing with emotional stimulus (ES) and without
      emotional stimulus (NES). Muscle activity was recorded by use of an ambulatory
      four-channel monitoring system (Physiometer PHY 400, Premed, Norway). Seven
      advanced student singers (three males and four females) participated as subjects.
      Four sample performances were performed: (1) extreme tones, (2) swell tones, (3)
      arpeggio, and (4) glissando. All sample performances were sung on the vowel /a:/.
      We conclude that classical singers change their breathing pattern when they
      vocalize using ES compared with using NES. The results imply that vocalizing
      using ES facilitates a more prominent role for LOBL activity in the positioning
      of the abdominal wall and thorax than observed when vocalizing using NES.

PMID- 18346868
TI  - Effect of pregnancy on the speaking voice.
AB  - The study aims to investigate the vocal symptoms and acoustic changes in pregnant
      women pre- and postpartum in comparison to the controls. A total of 25 pregnant
      women who presented for delivery were enrolled in this study. Twenty-one
      nonpregnant women were matched as controls. Vocal symptoms such as hoarseness,
      vocal fatigue, and aphonia were assessed. Acoustic analysis included fundamental
      frequency (F(0)), habitual pitch, relative average perturbation (RAP), shimmer,
      noise-to-harmony ratio (NHR), and maximum phonation time (MPT). There were no
      significant differences in the incidence of vocal symptoms in pregnant women
      versus controls. However, vocal fatigue was more prevalent in the pregnant group.
      With respect to the acoustic parameters, there was a significant decrease in the
      MPT at term. The rest of the variables were comparable. Postpartum, the MPT
      significantly increased and there was an increase in F(0) and a significant
      decrease in the voice turbulence index (VTI). Pregnant women have more vocal
      fatigue and a reduction in MPT compared to the controls. Immediately after
      delivery, there is a significant increase in MPT.

PMID- 18346869
TI  - The effect of anchor modality on the reliability of vocal severity ratings.
AB  - The purpose of this study was (1) to confirm if anchors (ie, perceptual
      references) and training affect the inter- and intrarater reliability of
      perceptual analysis of various voice types and severities compared to receiving
      training alone, and (2) to determine whether the modality in which the anchor is
      presented affects rater reliability. In this study, modality refers to whether
      the anchor is presented auditorily, visually via a written definition (a textual
      anchor), or a combination of both anchor types. A randomized multigroup
      comparison was performed. Forty inexperienced judges were selected to rate 36
      sustained vowel voice samples of various voice types (ie, normal, breathy,
      hoarse, and rough) in terms of perceived vocal severity using four different
      methods (No Anchor, Textual Anchor, Auditory Anchor, and Combined
      Textual/Auditory Anchors). Subjects were randomly assigned to one of the four
      conditions. Before the rating task, all subject groups received a brief training
      sessions (15-20 minutes in duration) in which voice quality type and severity
      definitions were provided and representative voice samples were listened to. A
      computer program was developed to present anchors in the form of an auditory
      sample, written definition, or both. A no anchor condition was also presented.
      Results indicated that the combination of training and anchors significantly
      improves the interrater reliability of perceptual voice ratings. In addition, the
      use of auditory anchors resulted in 95% confidence intervals that were
      significantly smaller for rating mild voice disorders, and both breathy and
      hoarse voice qualities. Textual anchors did appear to show some improvement over
      training alone (ie, no anchors), but were generally not as strong as the use of
      auditory anchors. However, the combination of textual and auditory anchors
      resulted in the greatest degree of interrater reliability as assessed via mean
      correlations. The ratings produced by the Auditory and Combined Anchor groups
      were also observed to have significantly smaller 95% confidence intervals for the
      rating of mildly dysphonic voice than the No Anchor or Textual Anchor groups,
      indicating greater consistency and increased precision of ratings for this level
      of severity. Anchors were not only useful in improving measures of reliability
      among judges, but were also able to do so without significantly increasing the
      amount of time that the judges had to spend on the rating tasks. No significant
      effect of anchors was observed for measures of intrarater reliability. The use of
      perceptual anchors (in particular, auditory anchors), in conjunction with
      training and computerized rating procedures, may provide the consistent
      methodology necessary to improve the reliability of perceptual judgments.
      Although textual anchors were not as effective as auditory anchors, the
      combination of auditory and textual information may result in overall
      improvements in interrater reliability.

PMID- 18346870
TI  - Granular cell tumors of the larynx: diagnosis and management.
AB  - In this case study, a retrospective review of chart and literature was done to
      discuss the presentation and treatment of granular cell tumors of the larynx. One
      patient was diagnosed and treated successfully with surgical resection of a
      laryngeal granular cell tumor. Excellent voice recovery was obtained and there is
      no evidence of recurrence 6 months after surgery. Granular cell tumors should be
      considered in the differential diagnosis of laryngeal masses, particularly in the
      posterior glottis.

PMID- 18346871
TI  - Acoustic analysis in asthmatics and the influence of inhaled corticosteroid
      therapy.
AB  - The impact of sustained inhaled corticosteroid (ICS) therapy on the larynx and
      pharynx was assessed using a prospective, cross-sectional, and investigator
      blinded study conducted at the University Hospital Aintree, Liverpool, UK. Forty
      six adults recruited from two local general practices and from general ENT
      clinics at our University hospital were investigated for the study. Patients were
      allocated to three groups according to ICS use. Laryngeal effects were measured
      by correlating the results of a vocal performance questionnaire, a respiratory
      symptom questionnaire, and measurements obtained by computerized speech analysis.
      Sustained vowels and connected speech were analyzed in normal and asthmatic
      subjects. Acoustic analysis was correlated with cellular markers of inflammation
      after biopsy. Regular ICS users had significantly more pharyngeal inflammation
      and throat discomfort (P<0.0001). Vocal performance was also worse in this group
      (P<0.0001). They were more likely to have hoarseness, weakness of voice, aphonia,
      sore throat, throat irritation, and cough (P<0.0001). All these variables were
      directly related to one another (P<0.0001). Multiple linear regression analysis
      showed that jitter was a good objective measure of hoarseness (P<0.05). Regular
      ICS users were significantly more likely to have abnormal jitter, shimmer, and
      closed-phase quotient scores (P<0.0001). There was no difference between the
      groups in the observed parameters of inflammation (P>0.01). A higher pharyngitis
      score did not correlate with any of the histological markers of inflammation
      (P>0.01). Local side effects are more common in asthmatics that use ICS
      regularly. Measures of laryngeal function are significantly worse in regular ICS
      users. However, histological markers and oropharyngeal redness are not reliable
      measures of inflammation.

PMID- 18346872
TI  - Vocal fold mucosa "blue lines" observed on contact telescopy at Reinke's edema.
AB  - Reinke's space is a highly specific structure critical for the function of the
      vocal fold, involved in a majority of pathological changes of the larynx. The aim
      of the study was to contribute to the understanding of edematous areas of vocal
      fold mucosa in patients with Reinke's edema using contact telescopy (ConTel). The
      edematous tissue which could be identified grossly by microlaryngoscopy under
      general anesthesia was stained topically with methylene blue and then examined
      using ConTel. The observed changes on contact images were further correlated with
      corresponding histological sections of biopsied edematous tissue. In patients
      with Reinke's edema examined using ConTel, we observed longitudinal arranged
      mucosal "blue lines" (BL). In the histological sections of edematous tissue
      showing the BL on ConTel, we almost regularly observed well-developed hollow
      spaces in subepithelia. Also, they were regularly oriented from the middle of the
      membranous portion of the vocal fold toward the arcuate line distributed almost
      parallel to the free edge of the vocal fold. BL were a specific feature of
      Reinke's edema as they were not found in control groups with normal vocal fold
      mucosa and with vocal fold polyps. For the first time we are describing a new
      superficial morphological feature of Reinke's edema. The BL could present
      epithelial ConTel markers of the area between two enlarged neighboring
      subepithelial crevices of Reinke's space, as indicated on histological sections.
      Further characterization of BL is required for the understanding of their role in
      Reinke's edema.

PMID- 18346873
TI  - Three-dimensional reconstruction of the pancreas and its surrounding structures.
AB  - In order to establish a visible three-dimensional model of the pancreas and its
      surrounding structures, successive cross-sectional images were retrieved from the
      first data set of a visible Chinese woman, and a visible model of the pancreas
      and its surrounding structures was established. Finally three-dimensional
      reconstruction of the pancreas and its surrounding structures was carried out.
      The reconstructed, three-dimensional model of the pancreas and its surrounding
      structures can reveal both single and multiple organs with some of the structures
      being transparent. Moreover, the model can be rotated and sliced successively in
      any direction.

PMID- 18346874
TI  - Defective formation of PKA/CnA-dependent annexin 2-S100A10/CFTR complex in
      DeltaF508 cystic fibrosis cells.
AB  - Cystic fibrosis (CF) is characterised by impaired epithelial ion transport and is
      caused by mutations in the cystic fibrosis conductance regulator protein (CFTR),
      a cAMP/PKA and ATP-regulated chloride channel. We recently demonstrated a
      cAMP/PKA/calcineurin (CnA)-driven association between annexin 2 (anx 2), its
      cognate partner -S100A10 and cell surface CFTR. The complex is required for CFTR
      and outwardly rectifying chloride channel function in epithelia. Since the
      cAMP/PKA-induced Cl(-) current is absent in CF epithelia, we hypothesized that
      the anx 2-S100A10/CFTR complex may be defective in CFBE41o cells expressing the
      commonest F508del-CFTR (DeltaF-CFTR) mutation. Here, we demonstrate that, despite
      the presence of cell surface DeltaF-CFTR, cAMP/PKA fails to induce anx 2
      S100A10/CFTR complex formation in CFBE41o- cells homozygous for F508del-CFTR.
      Mechanistically, PKA-dependent serine phosphorylation of CnA, CnA-anx 2 complex
      formation and CnA-dependent dephosphorylation of anx 2 are all defective in
      CFBE41o- cells. Immunohistochemical analysis confirms an abnormal cellular
      distribution of anx 2 in human and CF mouse epithelia. Thus, we demonstrate that
      cAMP/PKA/CnA signaling pathway is defective in CF cells and suggest that loss of
      anx 2-S100A10/CFTR complex formation may contribute to defective cAMP/PKA
      dependent CFTR channel function.

PMID- 18346875
TI  - cAMP-induced Epac-Rap activation inhibits epithelial cell migration by modulating
      focal adhesion and leading edge dynamics.
AB  - Epithelial cell migration is a complex process crucial for embryonic development,
      wound healing and tumor metastasis. It depends on alterations in cell-cell
      adhesion and integrin-extracellular matrix interactions and on actomyosin-driven,
      polarized leading edge protrusion. The small GTPase Rap is a known regulator of
      integrins and cadherins that has also been implicated in the regulation of actin
      and myosin, but a direct role in cell migration has not been investigated. Here,
      we report that activation of endogenous Rap by cAMP results in an inhibition of
      HGF- and TGFbeta-induced epithelial cell migration in several model systems,
      irrespective of the presence of E-cadherin adhesion. We show that Rap activation
      slows the dynamics of focal adhesions and inhibits polarized membrane protrusion.
      Importantly, forced integrin activation by antibodies does not mimic these
      effects of Rap on cell motility, even though it does mimic Rap effects in short
      term cell adhesion assays. From these results, we conclude that Rap inhibits
      epithelial cell migration, by modulating focal adhesion dynamics and leading edge
      activity. This extends beyond the effect of integrin affinity modulation and
      argues for an additional function of Rap in controlling the migration machinery
      of epithelial cells.

PMID- 18346876
TI  - Trapezius muscle innervation from the spinal accessory nerve and branches of the
      cervical plexus.
AB  - The aim of this study was to demonstrate the extent of motor innervation of the
      trapezius muscle from the accessory nerve and branches of the cervical plexus
      using intraoperative electroneurography and histochemical staining. In 34
      patients during radical neck dissection the accessory nerve and C2-C4 branches
      running to the trapezius were identified and stimulated. Potentials were
      registered under three conditions: intact accessory nerve, section of superior
      part of communication between the nerve and the cervical branches, and complete
      section of the nerve. Projections that did not elicit responses were analyzed for
      acetylcholinesterase activity. Before cutting the accessory nerve, its
      stimulation led to a recordable contraction in all parts of the trapezius muscle
      in all patients. C2 contributions were seen in 15, C3 in 21 and C4 in 20
      patients. After sectioning of the upper half of the nerve, the results were
      similar. After the nerve was completely cut, C2 contributions were seen in only 2
      patients, but C3 were seen in 20 patients and C4 in 19 patients. Histochemical
      staining revealed that the branches with no responses contained both motor and
      sensory axons. The accessory nerve provides the main motor input to the trapezius
      muscle, but preservation of the C2-C4 branches to the muscle during modified neck
      dissection should improve outcomes.

PMID- 18346877
TI  - Decreased gene expression of human beta-defensin-1 in the development of squamous
      cell carcinoma of the oral cavity.
AB  - The aim of this study was to investigate the gene expression of human beta
      defensin-1, -2, -3 (hBD-1, -2, -3), interleukin-1beta, tumour necrosis factor
      alpha and cyclooxygenase-2 in oral squamous cell carcinoma (OSCC) compared to
      benign and premalignant lesions as well as healthy controls. Biopsies of healthy
      gingiva (n=5), irritation fibroma (n=5), leukoplakia (n=5) and OSCC (n=5) were
      obtained during routine surgical procedures. RNA was extracted according to
      standard protocols and transcripts of hBD-1, -2, -3, interleukin-1beta, tumour
      necrosis factor-alpha and cyclooxygenase-2 were analysed by real-time polymerase
      chain reaction. The expression of hBD-1 was reduced in all lesions (5-fold in
      irritation fibroma and 2.5-fold in leukoplakia), but most significantly (50-fold)
      in OSCC. hBD-1 appears to play a role in the development of OSCC. The loss of its
      function might contribute to the malignant progression of these tumours.

PMID- 18346878
TI  - Co-expression of nerve growth factor and p75NGFR in the inferior alveolar nerve
      after mandibular distraction osteogenesis.
AB  - During mandibular distraction osteogenesis (DO), the inferior alveolar nerve
      (IAN) is damaged during distractor activation, but spontaneously recovers during
      consolidation. Although many neurotrophic factors are known to play critical
      roles, there have been few studies on the mechanism of peripheral nerve recovery
      after DO. The aim of this study was to observe the expression pattern of p75NGFR
      (low-affinity receptor of NGF) and to detect autocrine growth activity in IANs
      following mandibular DO. Unilateral mandibular distractions (0.5mm each, twice
      per day for 10 days) were conducted on eight mongrel dogs. Two each were killed
      at 7, 14, 28 and 56 days after completing distraction. The distracted IAN and
      contralateral control nerve were harvested. Immunohistochemical staining was
      performed to determine p75NGFR expression, and double immunofluorescent staining
      to detect NGF and p75NGFR co-expression. Levels of p75NGFR expression were found
      to be significantly elevated at 7 and 14 days in Schwann cells located in the
      outer layer of axon, but were almost undetectable at 28 and 56 days. In double
      immunofluorescent images, the co-expression of NGF and p75NGFR was also detected
      at 7 and 14 days. p75NGFR plays an important role in remyelination due to its
      abundant expression in Schwann cells of damaged nerves, and NGF is an autocrine
      growth factor present in distracted IANs during the early consolidation period
      after mandibular DO.

PMID- 18346879
TI  - Styloid process osteochondroma.
AB  - Osteochondroma, a benign tumor of the skeleton and auxiliary tissues, is usually
      seen around the epiphysis of long bone, flat pelvis, scapula and transverse
      process of vertebra, but seldom in the head and neck region. The incidence of
      osteochondroma in the jaw bone only accounts for 0.6% of the whole body
      incidence, with rare reports of osteochondroma protruding into the oral cavity.
      Primary osteochondroma in the styloid process has not been reported until now. A
      case of styloid process osteochondroma and its surgical removal are here
      described.

PMID- 18346880
TI  - Increased bone contact to a calcium-incorporated oxidized commercially pure
      titanium implant: an in-vivo study in rabbits.
AB  - The aim of this study was to evaluate the bone response to an oxidized titanium
      implant (Ox) and a calcium-incorporated oxidized titanium implant (Ca). A blasted
      titanium implant (Bl) was used as control. The implants were topographically
      characterized using an optical interferometer and placed: one in each distal
      femoral metaphysis and two in each proximal tibial metaphysis in rabbits. The
      rabbits were killed 12 weeks after implant insertion, and the implants and their
      surrounding tissues were removed en bloc for histomorphometrical evaluations.
      Topographical evaluation revealed three different surfaces: average height
      deviation (S(a), microm) values for Ca:Ox:Bl implants were 0.3:0.6:0.9, developed
      surface area ratios (%) 17:44:31, number of summits per microm(2) 208:136:118,
      and core fluid retention index values 1.33:1.33:1.38. The mean percentages of
      bone contact to the implants placed in the tibia (Ca:Ox:Bl) were 47:30:34 and to
      the implants placed in the femur (Ca:Ox) 32:20. The mean percentages of
      surrounding bone area for the implants placed in the tibia were 40:47:37 and for
      the implants placed in the femur 43:46. A significant increase in bone contact
      was found for smooth (S(a) <0.5 microm) but more densely peaked calcium
      incorporated oxidized implants when compared to slightly rougher (S(a)=0.5-1.0
      microm) oxidized or blasted implants.

PMID- 18346881
TI  - The effect of DHEA complementary treatment on heroin addicts participating in a
      rehabilitation program: a preliminary study.
AB  - We evaluated the effect of DHEA complementary treatment in opiate addicts
      undergoing detoxification. DHEA (100 mg/day) or placebo was added to the routine
      medication protocol in a randomized, double blind controlled study. Follow-up for
      12 months was conducted. Two separate DHEA-treated subgroups were identified by
      the Fuzzy clustering method: one showed statistically significant improvement in
      the severity of withdrawal symptoms, depression and anxiety scores (n=34; p<0.001
      for all) and the other subgroup deteriorated in all measures (n=15). DHEA at the
      end of the detoxification program showed a tendency towards correlation with the
      duration of abstinence (r=0.6843; p>0.05; n=6), while a negative correlation was
      obtained with the cortisol level (r=-0.900; p=0.005, n=8). The completion-rate of
      the DHEA-improved subgroup was greater than in the DHEA-deteriorated subgroup
      (64.7% vs. 33.3%, respectively). The influence of supplementary DHEA treatment
      was mostly effective in heroin addicts who had not previously used either cocaine
      or benzodiazepines and who had experienced only few withdrawal programs.

PMID- 18346882
TI  - In vitro response of hFOB cells to pamidronate modified sodium silicate coated
      cellulose scaffolds.
AB  - The aim of the present study was to evaluate the suitability of cellulose-based
      scaffolds coated with pure sodium silicate gel and sodium silicate gels
      accumulated with different concentrations of the bisphosphonate pamidronate as
      scaffolds for attachment, proliferation and differentiation of human fetal
      osteoblasts (hFOB 1.19). Human osteoblasts were cultured in vitro for a period up
      to 14 days on different cellulose scaffolds. Unmodified and sodium silicate
      coated cellulose scaffolds were used as control. Two surface-coated modifications
      of cellulose were applied. The scaffolds were coated in a modified two-step dip
      coating process with pure sodium silicate gel and pamidronate enriched sodium
      silicate gel, respectively. In order to investigate the influence of the
      pamidronate, concentrations of 0.667 mg Na-pamidronate/ml sodium silicate
      solution, 0.333 mg Na-pamidronate/ml sodium silicate solution and 3.33 x 10(-3)
      mg Na-pamidronate/ml sodium silicate solution were used for the coating process.
      Cell proliferation, vitality and attachment were examined by means of cell
      counting, WST-1 test, fluorescence and scanning electron microscopy. The relative
      grade of differentiation of hFOB cells was examined by using quantitative real
      time polymerase chain reaction (qRT-PCR) analysis for the gene expression of
      alkaline phosphatase and osteocalcin. Proliferation and differentiation of human
      osteoblasts was enhanced by the sodium silicate coatings accumulated with
      pamidronate compared to pure sodium silicate coatings. There was a reciprocal
      correlation of vitality with the concentration of pamidronate. The highest
      vitality was found on surfaces with the lowest pamidronate accumulation. Alkaline
      phosphatase, an early differentiation marker, was overexpressed after 7 days in
      cells on all pamidronate-containing surfaces (up to 350% compared to untreated
      cellulose). Osteocalcin, a late differentiation marker, was overexpressed after
      14 days in cells on all coated surfaces (up to 300,000% compared to untreated
      cellulose). The results indicate that due to the modified coating procedure a
      homogeneous coating and thus, an enhancement of cell attachment and subsequent
      cellular functions can be achieved. Low concentrations of pamidronate seem to
      have a relevant effect on cell proliferation and vitality and, therefore, can be
      recommended for the improvement of the properties of a biomaterial.

PMID- 18346883
TI  - Pancreatic cancer within a UK cancer network with special emphasis on locally
      advanced non-metastatic pancreatic cancer.
AB  - AIMS: The outcome of patients with pancreatic cancer from an unselected
      population within a UK region has not previously been reported. We undertook a
      review of pancreatic cancer in southeast Wales, with an emphasis on locally
      advanced non-metastatic pancreatic cancer (LANPC) in an attempt to define a
      subgroup of patients who would probably benefit from multi-modality treatment.
      MATERIALS AND METHODS: Case notes of patients referred to Velindre Hospital
      between 1 January 2002 and 31 December 2005 were reviewed. Data on patient
      demographics, tumour characteristics, treatment, treatment response and overall
      survival were collected. The Log-rank test was used to compare survival between
      groups and Cox regression was used to evaluate whether age, gender, tumour site
      and treatment response correlated with overall survival in LANPC. RESULTS: Of the
      354 referrals (complete data on 315 patients), 93% were inoperable and 51% of
      inoperable patients received active treatment (149/294). One hundred and fourteen
      patients out of 315 (36%) had LANPC and 72/114 (64%) were fit for active
      treatment, including chemotherapy (n=66) and chemoradiotherapy (CRT) (n=6). The
      median survival of patients with LANPC was 7.4 months (95% confidence interval
      6.4-8.5). Survival for patients receiving chemotherapy, CRT and no treatment was
      9.2 (7.5-10.7), 12.6 (6.1-19.1) and 4.5 (3.7-5.3) months, respectively. Overall
      survival of patients who had non-progressive disease after initial chemotherapy
      was significantly better than those who progressed (11.8 vs 6.6 months, P=0.01).
      Of the 180/315 (57%) patients presenting with metastatic disease, 43% received
      active treatment. Overall survival of metastatic patients was 2.8 months (2.3-3.2
      months); for those receiving active treatment, this was 5.6 months (5.1-6.1
      months) and for those receiving active supportive care 1.8 months (1.6-2.0
      months). CONCLUSIONS: In this UK network, about half of the patients received
      active treatment. Although the overall outcome was poor, that of treated patients
      was comparable with published studies. For patients with LANPC, the initial
      response or disease stabilisation on chemotherapy defined a subset of patients
      who had better outcome. The role of CRT over and above chemotherapy needs to be
      defined through trials that should include a neoadjuvant 'chemotherapy-only'
      phase to select out patients who benefit from multi-modality treatment.

PMID- 18346884
TI  - Phylogeography and biogeography of fungi.
AB  - The rigorous study of processes shaping geographic distributions of lineages is a
      relatively new and emerging field in mycology. While it was previously generally
      believed that most fungi have wide distributions and largely unstructured
      populations, recent studies have shown that this is not the case. The study of
      distributions in tandem with molecular approaches to phylogeny has recently made
      substantial advances to our understanding of the diversity and biogeography of
      fungi. Comprehensive species inventories have provided a better picture of the
      actual distribution of these organisms, while robust phylogenies based on
      molecular characters have provided both data that allow interpretation of current
      distributions and testable hypotheses regarding the processes responsible for
      distribution patterns. This commentary provides an introduction to five papers in
      this issue of Mycological Research that focus on fungal phylogeography. These
      papers are based on oral contributions given at two symposia at the International
      Mycological Congress (IMC8) held in Cairns (Australia) in August 2006.

PMID- 18346885
TI  - Reverse the curse--the role of deubiquitination in cell cycle control.
AB  - Reversible protein ubiquitination is a crucial mechanism regulating the
      progression through the eukaryotic cell cycle. Ubiquitin-dependent signaling is
      terminated by specific deubiquitinating enzymes (DUBs), which now are known to be
      integral components of the core cell cycle machinery and cell cycle checkpoints.
      The importance of DUBs for cell cycle control is underscored by their frequent
      misregulation in cancer. Here, we discuss the role of deubiquitinating enzymes in
      controlling proliferation.

PMID- 18346886
TI  - Use of biosurfactants from urban wastes compost in textile dyeing and soil
      remediation.
AB  - A compost isolated humic acid-like (cHAL) material was pointed out in previous
      work for its potential as auxiliary in chemical technology. Its potential is
      based on its relatively low 0.4gL(-1) critical micellar concentration (cmc) in
      water, which enables cHAL to enhance the water solubility of hydrophobic
      substances, like phenanthrene, when used at higher concentrations than 0.4gL(-1).
      This material could be obtained from a 1:1 v/v mixture of municipal solid and
      lignocellulosic wastes composted for 15 days. The compost, containing 69.3%
      volatile solids, 39.6% total organic C and 21C/N ratio, was extracted for 24h at
      65 degrees C under N2 with aqueous 0.1molL(-1) NaOH and 0.1molL(-1) Na4P2O7, and
      the solution was acidified to separate the precipitated cHAL in 12% yield from
      soluble carbohydrates and other humic and non-humic substances. In this work two
      typical applications of surfactants, i.e., textile dyeing (TD) and soil
      remediation by washing (SW), were chosen as grounds for testing the performance
      of the cHAL biosurfactant against the one of sodium dodecylsulfate (SDS), which
      is a well established commercial synthetic surfactant. The TD trials were carried
      out with nylon 6 microfiber and a water insoluble dye, while the SW tests were
      performed with two soils contaminated by polycyclic aromatic hydrocarbons (PAH)
      for several decades. Performances were rated in the TD experiments based on the
      fabric colour intensity (DeltaE) and uniformity (sigmaDeltaE), and in the SW
      experiments based on the total hydrocarbons concentration (CWPAH) and on the
      residual surfactant (Cre) concentrations in the washing solution equilibrated
      with the contaminated soils. The results show that both cHAL and SDS exhibit
      enhanced performance when applied above their cmc values. However, while in the
      TD case a significant performance effect was observed at the surfactants cmc
      value, in the SW case the required surfactants concentration values were
      equivalent to 25-125xcmc for cHAL and to 4-22xcmc for SDS. The vis-a-vis
      comparison of the two surfactants gave the following results: in the TD case the
      cHAL biosurfactant at 0.4gL(-1) yields good colour intensity and equal colour
      uniformity as SDS at 5gL(-1), in the SW case cHAL was found to enhance CWPAH by a
      factor of 2-4 relative to SDS with one soil, whereas with the other soil the two
      surfactants behaved similarly. The Cre data, however, showed that both soils
      absorbed by far more SDS (68-95%) than cHAL (12-54%). The results point out
      intriguing technological and environmental perspectives deriving from the use of
      compost isolated biosurfactants in the place of synthetic surfactants.

PMID- 18346887
TI  - Comparison of old and new municipal solid waste management systems in Denizli,
      Turkey.
AB  - Rapid economic growth, increasing population and change in living standards
      contribute to increasing the generation rate of municipal solid waste (MSW) in
      Denizli city, like other Turkish cities. The improper and poor MSW management
      system (old system) in Denizli caused environmental problems originating from the
      uncontrolled release of methane and leachate. In addition, the disposal of
      recyclable materials in unsanitary landfills is responsible for the consumption
      and destruction of natural sources. This paper presents a general overview of old
      and new MSW management practices in Denizli. Detailed data on MSW management
      practices including collection, transportation, disposal and recycling have been
      presented. The amount of solid waste generated in Denizli over the last decade
      has increased steadily over the years, from 108,500 tons in 1995 to 179,495 tons
      in 2006. The average MSW generation rate was found to be 1.23kg/day per capita.
      The major constituent of MSW in Denizli is food waste, but the percentage of
      recyclable waste has increased significantly recently. Except for metal wastes,
      the percentages of recyclable waste materials in Denizli are higher than in all
      neighborhood cities. The objective of this study is to compare the old and new
      MSW management systems in Denizli city. The MSW management system has been
      changed entirely last five years. A dumpsite was closed and a sanitary landfill
      with a composting facility was constructed. In addition, source separated
      collection has been carried out since 2002. The quantity of recyclable waste
      collected increased from 195 to 1549 tons. The amount of recyclable waste will
      continue to be increased by expanding the source separation collection system to
      all the districts of the city and preventing scavenging. Thus, revenue from
      recyclable waste ($7227 in 2006) is expected to increase. In addition, the
      capacity of the composting facility will be increased. Most importantly,
      information to increase public participation and awareness in municipal recovery
      programs has to be provided.

PMID- 18346888
TI  - A novel immobilization strategy using oligonucleotide as linker for small
      molecule microarrays construction.
AB  - A novel immobilization method based on oligonucleotide as linker has been
      developed for small molecule microarrays (SMMs) construction. The oligonucleotide
      tail was employed as a linker in solid-phase synthesis. Small molecules could be
      easily conjugated at the 5' end of the oligonucleotide, previously modified with
      a functional group. Being a reactive species, the oligonucleotide was activated
      by UV irradiation, for the attachment of the conjugate to the slide surface. The
      method was successfully applied to structurally distinct small molecules,
      including biotin, antibiotic and drug. This immobilization strategy showed high
      efficiency, 1.1fmol of small molecules in the spotting solution per spot gave a
      detectable signal (mean S/N=10.9). The results suggest that it is very promising
      for exploring interaction between small molecules and proteins, and high
      throughput detecting the chemical compounds.

PMID- 18346889
TI  - Evolution of non-dissolved particulate organic matter during composting of sludge
      with straw.
AB  - Long term composting induces loss of C and organic matter stabilisation. These
      two processes may have opposite effects on long term carbon storage in soils. To
      check whether raw materials should be composted or not before being spread on the
      soil, changes in particle size fractions were quantified during composting of 9
      tons of sewage sludge and straw. Both the mass of the fine fraction (<2 microm)
      and the amount of carbon contained in it increased after seven months,
      respectively, +37% and +43%. The fine fraction contributes to carbon
      sequestration. A literature review supported the assumption that composting
      should increase long term C storage. Nevertheless, soil texture or agricultural
      practices modify the behaviour of this fraction. Thus, the fractionation method
      used for soils is relevant to predict the effect of composting as a mitigation
      option in greenhouse gas reduction strategies, but is not sufficient in itself.

PMID- 18346890
TI  - Screening and isolation of an organic solvent-tolerant bacterium for high-yield
      production of organic solvent-stable protease.
AB  - Forty-three strains were screened from crude oil-contaminated samples by toluene
      and cyclohexane enrichment in medium. Ten of these strains demonstrated high
      protease activity on skim-milk agar. Among them, the PT121 isolate, identified as
      Pseudomonas aeruginosa, was selected based on its extracellular protease
      stability in the presence of hydrophilic organic solvents. The crude protease
      also retained most of its activity up to at least 14 days in the presence of
      various organic solvents at 50% concentration, and the protease activity in
      production medium was 10,876U/ml after 72h incubation. This protease showed high
      activity as a catalyst for aspartame precursor Cbz-Asp-Phe-NH2 synthesis in the
      presence of 50% dimethylsulfoxide (DMSO).

PMID- 18346891
TI  - Production and characterization of cellulolytic enzymes from the
      thermoacidophilic fungal Aspergillus terreus M11 under solid-state cultivation of
      corn stover.
AB  - The production of extracellular cellulases by a newly isolated thermoacidophilic
      fungus, Aspergillus terreus M11, on the lignocellulosic materials was studied in
      solid-state fermentation (SSF). The results showed that the high-level cellulase
      activity was produced at 45 degrees C pH 3 and moisture 80% with corn stover and
      0.8% yeast extract as carbon and nitrogen sources. 581 U endoglucanase activity,
      243 U filter paper activity and 128 U beta-glucosidase activity per gram of
      carbon source were obtained in the optimal condition. Endoglucanase and beta
      glucosidase exhibited their maximum activity at pH 2 and pH 3, respectively, and
      both of them showed remarkable stability in the range of pH 2-5. The activities
      of endoglucanase and beta-glucosidase were up to the maximum at 70 degrees C and
      maintained about 65% and 53% of their original activities after incubation at 70
      degrees C for 6h. The enzyme preparations from this strain were used to hydrolyze
      Avicel. Higher hydrolysis yields of Avicel were up to 63% on 5% Avicel (w/v) for
      72 h with 20 U FPase/g substrate.

PMID- 18346892
TI  - Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl
      peptidase IV inhibitors.
AB  - A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been
      developed from a small fragment hit using structure-based drug design. A highly
      versatile synthetic route was created for the development of SAR, which led to
      the discovery of potent and selective inhibitors with excellent pharmaceutical
      properties.

PMID- 18346893
TI  - Pharmacophore identification of Raf-1 kinase inhibitors.
AB  - A three-dimensional pharmacophore model was developed based on 25 currently
      available Raf-1 kinase inhibitors. The best pharmacophore hypothesis (Hypo1),
      consisting of four chemical features (one hydrogen-bond acceptor, one hydrogen
      bond donor, and two hydrophobic groups), has a correlation coefficient of 0.972.
      The results of our study provide a valuable tool in designing new leads with
      desired biological activity by virtual screening.

PMID- 18346894
TI  - Ageing and the regulation of protein synthesis: a balancing act?
AB  - Ageing in diverse species ranging from yeast to humans is associated with
      extensive changes in both general and specific protein synthesis. Accumulating
      evidence now indicates that these alterations are not simply a corollary of the
      ageing process but, rather, they have a causative role in senescent decline.
      Indeed, interfering with mRNA translation significantly influences longevity.
      Interestingly, the mechanisms that control mRNA translation interface with
      intricate, conserved signalling pathways and specific conditions that regulate
      ageing, such as the insulin-insulin growth factor 1 signalling pathway and
      caloric restriction. This emerging relationship reveals that protein synthesis is
      a novel determinant of ageing in diverse organisms such as yeast, worms, flies
      and mice and can thus be considered as a universal component of the ageing
      process.

PMID- 18346895
TI  - Paramyxoviruses: different receptors - different mechanisms of fusion.
AB  - Paramyxovirus-mediated membrane fusion usually requires an interaction between
      the viral-attachment and -fusion proteins. The mechanism by which this
      interaction regulates fusion differs between paramyxoviruses that bind to sialic
      acid-containing receptors and those that recognize specific proteins. The
      recently solved structure of the globular head of the measles virus hemagglutinin
      suggests that this difference might be related to the location of the receptor
      binding sites on the attachment proteins of the two classes of paramyxoviruses.

PMID- 18346896
TI  - Rationally designed PKA inhibitors for positron emission tomography: Synthesis
      and cerebral biodistribution of N-(2-(4-bromocinnamylamino)ethyl)-N-[11C]methyl
      isoquinoline-5-sulfonamide.
AB  - Protein kinase A (PKA) is an important signal transduction target for drug
      development because it influences critical cellular processes implicated in
      neuropsychiatric illnesses such as major depressive disorder. The goal of the
      present study was to develop the first imaging agent for measuring the levels of
      PKA with positron emission tomography (PET). By rational derivatization of 5
      isoquinoline sulfonamides, it was found that the introduction of a methyl group
      to the sulphonamidic nitrogen on the known PKA inhibitors N-(2
      aminoethyl)isoquinoline-5-sulfonamide (H-9, 1) and N-(2-(4
      bromocinnamylamino)ethyl)isoquinoline-5-sulfonamide (H-89, 2), (yielding N-(2
      aminoethyl)-N-methyl-isoquinoline-5-sulfonamide (4) and N-(2-(4
      bromocinnamylamino)ethyl)-N-methyl-isoquinoline-5-sulfonamide (5), respectively)
      does not appreciably reduce in vitro potency toward PKA. We have facilitated the
      synthesis of 4 by reacting isoquinoline-5-sulfonyl chloride with N
      methylethylenediamine (20% yield). Several techniques were used to thoroughly
      characterize 4 including multi ((1)H, (13)C and (15)N) NMR spectroscopy and X-ray
      crystallography. Compound 4 and 1-(4-bromophenyl)-1-propen-3-yl bromide were
      reacted to produce 5 in 16% yield. Compound 2 was reacted with [(11)C]CH(3)I to
      prepare N-(2-(4-bromocinnamylamino) ethyl)-N-[(11)C]methyl-isoquinoline-5
      sulfonamide ([(11)C]5), with a decay-corrected radiochemical yield of 32%, based
      on [(11)C]CO(2). [(11)C]5 was produced with >98% radiochemical purity and
      1130mCi/mumol specific activity after 40min (end of synthesis). Conscious rats
      were administered [(11)C] 5 and sacrificed at 5, 15, 30 and 60min after
      injection. Radioactivity from all excised brain regions was <0.2%ID/g at all time
      points. The modest brain penetration of [(11)C]5 may limit its use for studying
      PKA in the central nervous system.

PMID- 18346897
TI  - Structure-antifungal activity relationship of His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2
      and analogues.
AB  - The synthesis, in vitro evaluation and conformational study of His-Phe-Arg-Trp
      Gly-Lys-Pro-Val-NH(2) and analogues acting as antifungal agents are reported.
      Among them, His-Phe-Lys-Trp-Gly-Arg-Phe-Val-NH(2) exhibited a moderate but
      significant antifungal activity against Cryptococcus neoformans, Candida albicans
      and Candida tropicalis. A theoretical study allows us to propose a biologically
      relevant conformation for these octapeptides acting as antifungal agents. In
      addition, these theoretical calculations allow us to determine the minimal
      structural requirements to produce the antifungal response and can provide a
      guide for the design of compounds with this biological activity.

PMID- 18346898
TI  - Synthesis of 1-substituted 3-pyridinylmethylidenylindolin-2-ones and 1
      substituted 3-quinolinylmethylidenylindolin-2-ones as the enhancers of ATRA
      induced differentiation in HL-60 cells.
AB  - As part of our continuing search for potential differentiation agents, 1-benzyl-3
      (4-pyridinylmethylidenyl)indolin-2-one (14) was selected as lead compound, and
      its new pyridinyl and quinolinyl analogs were synthesized and evaluated for
      differentiation-inducing activity toward HL-60 cells. Most of the tested
      compounds enhanced the ATRA-induced differentiation; among them, 1-(1
      phenylethyl)-3-(3-quinolinylmethylidenyl)indolin-2-one (25) was the most
      promising one. The two isomers, 25Z and 25E; consisting 25 were found to have
      similar differentiation activity. The combination of 25 with all trans retinoic
      acid (ATRA) was found to induce complete differentiation of HL-60 cells and
      arrest the cells in the G(0)/G(1) phase of the cell cycle. Beside its excellent
      differentiation activity, 25 also exhibited relatively low cytotoxicity toward
      normal cells. Therefore, compound 25 is recommended as a candidate for further
      development of novel enhancer of ATRA-induced differentiation in HL-60 cells.

PMID- 18346899
TI  - Ultrastructural analysis of midgut cells from Culex quinquefasciatus (Diptera:
      Culicidae) larvae resistant to Bacillus sphaericus.
AB  - The larvicidal action of the entomopathogen Bacillus sphaericus towards Culex
      quinquefasciatus is due to the binary (Bin) toxin present in crystals, which are
      produced during bacterial sporulation. The Bin toxin needs to recognize and bind
      specifically to a single class of receptors, named Cqm1, which are 60-kDa alpha
      glucosidases attached to the apical membrane of midgut cells by a
      glycosylphosphatidylinositol anchor. C. quinquefasciatus resistance to B.
      sphaericus has been often associated with the absence of the alpha-glucosidase
      Cqm1 in larvae midgut microvilli. In this work, we aimed to investigate, at the
      ultrastructural level, the midgut cells from C. quinquefasciatus larvae whose
      resistance relies on the lack of the Cqm1 receptor. The morphological analysis
      showed that midgut columnar cells from the resistant larvae are characterized by
      a pronounced production of lipid inclusions, throughout the 4th instar. At the
      end of this stage, resistant larvae had an increased size and number of these
      inclusions in the midgut cells, while only a small number were observed in the
      cells from susceptible larvae. The morphological differences in the midgut cells
      of resistant larvae found in this work suggested that the lack of the Cqm1
      receptor, which also has a physiological role as being an alpha-glucosidase, can
      be related to changes in the cell metabolism. The ultrastructural effects of Bin
      toxin on midgut epithelial cells from susceptible and resistant larvae were also
      investigated. The cytopathological alterations observed in susceptible larvae
      treated with a lethal concentration of toxin included breakdown of the
      endoplasmic reticulum, mitochondrial swelling, microvillar disruption and
      vacuolization. Some effects were observed in cells from resistant larvae,
      although those alterations did not lead to larval death, indicating that the
      receptor Cqm1 is essential to mediate the larvicidal action of the toxin. This is
      the first ultrastructural study to show differences in the cell morphology of
      resistant larvae and further investigation is needed to understand the impact of
      the lack of expression of midgut enzymes on the physiology of resistant insects.

PMID- 18346900
TI  - Quality audit programme for (99m)Tc and (131)I radioactivity measurements with
      radionuclide calibrators.
AB  - The use of radiopharmaceuticals in nuclear medicine for diagnosis and therapy has
      increased over the years with (99m)Tc and (131)I being most widely used. Quality
      audit programmes for radioactivity measurements of (131)I have been ongoing and
      the 12th audit was recently conducted among seventy nuclear medicine centres
      (NMC) in India. An audit for the activity measurements of (99m)Tc was conducted
      for the first time among ten NMCs in Mumbai, India. These programmes for
      radioactivity measurements have become very important to establish traceability
      of measurements to national and international standards and ensure accurate
      calibration of radionuclide calibrators. The results of both the audits are very
      encouraging. Ninety-four percent of the NMCs for (131)I activity measurements
      were within a window of +/-10% and for (99m)Tc one NMC was deviating more than +/
      10%. The methodology adopted for the audit and results are discussed in detail in
      this paper.

PMID- 18346901
TI  - CREPT-MCNP code for efficiency calibration of HPGe detectors with the
      representative point method.
AB  - The representative point method for the efficiency calibration of volume samples
      has been previously proposed. For smoothly implementing the method, a calculation
      code named CREPT-MCNP has been developed. The code estimates the position of a
      representative point which is intrinsic to each shape of volume sample. The self
      absorption correction factors are also given to make correction on the
      efficiencies measured at the representative point with a standard point source.
      Features of the CREPT-MCNP code are presented.

PMID- 18346902
TI  - Proficiency tests in the determination of activity of radionuclides in
      radiopharmaceutical products measured by nuclear medicine services in 8 years of
      comparison programmes in Brazil.
AB  - Proficiency tests were applied to assess the performance of 74 nuclear medicine
      services in activity measurements of (131)I, (123)I, (99)Tc(m), (67)Ga and
      (201)Tl. These tests produced 913 data sets from comparison programmes promoted
      by the National Laboratory for Ionizing Radiation Metrology (LNMRI) from 1999 to
      2006. The data were evaluated against acceptance criteria for accuracy and
      precision and assigned as Acceptable or Not acceptable accordingly. In addition,
      three other statistical parameters were used as complementary information for
      performance evaluation which related to normative requirements and to
      radionuclide calibrators. The results have shown a necessity to improve quality
      control procedures and unsatisfactory performances of radionuclide calibrators,
      which incorporate Geiger-Muller detectors.

PMID- 18346903
TI  - Modified forked flap for controlling columella length in cleft lip open
      rhinoplasty.
AB  - BACKGROUND & PURPOSE: Suturing the columellar flap after open rhinoplasty often
      reduces the tip projection gained, especially in patients with cleft lip
      deformity, in whom the columella is usually short and inelastic. A modification
      of the classical forked flap is proposed for controlling the tension created by
      the columellar suture. PATIENTS: Five patients aged from 17 to 35 years underwent
      surgery in the previous 2 years using the described techniques. METHODS: The
      columella incision followed the classic tepee shape, although the inverted V was
      extremely narrow and long, with its arms extending beyond the columellar rims,
      stopping at the base of the vestibule, then making acute angles and heading
      vertically towards the nostril tip, and continuing into the nostrils as normal
      marginal incisions. Consequently, a complete "W" was used, in which the lateral
      angles and arms lay in the nostrils, while the central inverted V was in the
      columella. The rhinoplasty was performed as planned and a triple "V-Y" suture was
      made. RESULTS: The technique provided real lengthening of the columella or, at
      least, it closed the columellar incision without tension, thereby preserving the
      tip projection. CONCLUSIONS: In open rhinoplasty on patients with cleft lip
      involvement a triple V-Y columellar suture preserves the surgically obtained
      columella length.

PMID- 18346904
TI  - Mechanical aspects of a multidirectional, angular stable osteosynthesis system
      and comparison with four conventional systems.
AB  - BACKGROUND: Following open reduction, internal fixation of fractures of the
      mandible is predominantly achieved using plates and screws. Today, a multitude of
      osteosynthesis systems are available on the market. One therapy modality,
      primarily developed for orthopaedic surgery, is using angular stable
      osteosynthesis plate systems. The dominating principle of these is the bond
      between screw and plate following insertion. This principle of an "internal
      fixateur" results in a more stable fixation of the fragments associated with less
      compression of the bone surfaces. MATERIAL: A new multidirectional osteosynthesis
      system (TiFix=Smartlock, Hamburg - Germany) was modified to fit the maxillofacial
      region and compared with four other well established osteosynthesis systems
      developed by Mondial, Medicon, Synthes, Leibinger-Stryker, one of these (Unilock
      by Synthes) being also angular stable. The resistance to deformation in varying
      directions was investigated following fixation in four different materials.
      RESULTS: The TiFix system proved more resistant to deformation even when mounted
      with fewer screws than the non-angular stable systems. CONCLUSION: This system
      results in greater stability even when fewer screws are used. For the clinician
      this means smaller access incisions, less soft tissue trauma, better aesthetic
      results, decreased duration of operation and a reduction of costs.

PMID- 18346906
TI  - Optimal initial treatment and clinical outcome of type A aortic intramural
      hematoma: a clinical review.
AB  - Intramural hematoma (IMH) of the aorta is a well-known variant of aortic
      dissection; however, the optimal initial treatment strategy for type A IMH
      remains controversial. An English language search of Medline for manuscripts on
      the treatments and outcomes of IMH with the keywords 'intramural hematoma',
      'ascending aorta or type A', 'aortic disease' with cross-references was performed
      for articles dating from January 1986 to September 2006. Primary outcomes of
      interest were initial treatment strategies as well as the early and overall
      mortality rates. Earlier publications studying overlapping patient groups from
      the same institutions were excluded. Case reports and small series of less than
      10 patients were not enrolled. Data from 328 reported cases in 12 studies were
      extracted. Initial surgery and medical treatment were performed for 168 (51.2%)
      and 160 (48.8%) patients, respectively. Nine out of 12 studies (75%) came from
      Asia. The early mortality rate was 10.1% (17/168) and 14.4% (23/160) in patients
      who received initial surgery and medical treatment, respectively (p=0.37). The
      optimal initial treatment strategy for type A IMH may still be individualized.
      Initial medical treatment and timed surgical therapy seems to be associated with
      higher early mortality rates in patients with type A IMH, even in a primarily
      Asian cohort. The impact of either initial treatment strategy on long-term
      survival must be evaluated in further study.

PMID- 18346907
TI  - The simultaneous presence of IL-1B and TNFA two-positions risk haplotypes
      enhances the susceptibility for celiac disease.
AB  - To assess the joint contribution of interleukin 1 beta (IL-1B) and tumor necrosis
      factor alpha (TNFalpha) to the genetic risk of developing celiac disease (CD), we
      analyzed four biallelic polymorphisms of TNFA and IL-1B genes in 228 patients and
      244 healthy controls. The individual contribution of TNFA -308A and IL-1B -511C
      alleles was weak (OR 1.47 and 1.66, respectively) and was null for TNFA -238 A/G
      and IL-1B +3953 C/T single nucleotide polymorphisms (SNPs). Due to the potential
      linkage disequilibrium between TNFA, human leukocyte antigen (HLA) -DQA1 and HLA
      DQB1 genes, only individuals carrying DQ2 antigen (DQ2-positive) were considered
      to perform haplotype analyses. Two-position risk haplotypes were first defined by
      the combined presence of -511C and +3953T alleles for IL-1B (OR 9.402) or -308A
      and -238A alleles for TNFA (OR 15.389). The TNFA/IL-1B combined haplotype
      stratified association analysis showed that the simultaneous presence of TNFA
      risk and IL-1B non-risk haplotypes (OR 13.32) but not TNFA non-risk and IL-1B
      risk haplotypes (OR 0.71) is associated with CD. Interestingly, our data suggest
      that the coexistence of both risk haplotypes seems to work synergistically (OR
      29.59), which enhances the risk of developing CD.

PMID- 18346908
TI  - TGF-beta1 targets the GSK-3beta/beta-catenin pathway via ERK activation in the
      transition of human lung fibroblasts into myofibroblasts.
AB  - Transforming growth factor-beta1 (TGF-beta1) is known to induce the transition of
      human lung fibroblasts to myofibroblasts, a primary event in the pathogenesis of
      idiopathic pulmonary fibrosis. The molecular pathways involved in myofibroblast
      transformation are only partially identified. We found that a 24-h treatment with
      TGF-beta1 (10 ng/ml) induced alpha-smooth actin (SMA) expression and collagen
      production in human lung fibroblasts. These effects were abrogated by PD98059, a
      specific inhibitor of the mitogen-activated protein kinase (MAPK) pathway. TGF
      beta1 treatment activated the MAPK pathway, as shown by an increased
      phosphorylation of extracellular-regulated kinases (ERK)1/2 after 30 min of
      exposure. TGF-beta1 also increased the expression of the Ser-9-phosphorylated
      inactive form of glycogen synthase kinase-3beta (GSK-3beta), an effect that was
      largely attenuated by PD98059. A nuclear translocation of beta-catenin in human
      lung fibroblasts was observed 2h after TGF-beta1 addition both by confocal
      microscopy and nuclear protein analysis. At this time, TGF-beta1 also increased
      the total levels of beta-catenin, an effect that was prevented by PD98059.
      Similarly to TGF-beta1, the GSK-3beta inhibitor lithium chloride (10mM),
      increased the total levels of beta-catenin and promoted alpha-SMA expression and
      collagen production. This study demonstrates that TGF-beta1 induces alpha-SMA
      expression and collagen production in human lung fibroblasts via ERK1/2
      activation, GSK-3beta inhibition and nuclear beta-catenin translocation. The
      evidence that the silencing of beta-catenin by siRNAs was able to prevent the
      induction of alpha-SMA expression in TGF-beta1-treated fibroblasts further
      supports the hypothesis of a contribution of the GSK-3beta/beta-catenin pathway
      in the pathogenesis of idiopathic pulmonary fibrosis.

PMID- 18346909
TI  - Does cigarette use influence adiposity or height in adolescence?
AB  - PURPOSE: To study the effect of cigarette use on height and adiposity in
      adolescents. METHODS: Data on cigarette use were collected every 3 months for 5
      years from adolescents initially 12-13 years of age. Height, weight, and triceps
      skinfold thickness were measured in survey cycles 1, 12, and 19. Multivariate
      linear regression models were fitted to estimate the association between
      cigarette use and the anthropometric measures in a dataset that pooled data over
      two time periods, from survey cycles 1-12 and from survey cycles 12-19. RESULTS:
      Data were available for 451 boys and 478 girls. Seven percent of boys and 14% of
      girls smoked > or =30 cigarettes per month on average during the first time
      period; 9% of boys and 18% of girls smoked > or =30 cigarettes per month on
      average during the second time period. In boys, a 100-cigarette per month
      increment in cigarette use over the preceding 2.5 years was independently
      associated with lower body mass index (-0.4 kg/m(2)) and shorter height (-0.7
      cm). In girls, cigarette use was not associated with height or adiposity.
      CONCLUSIONS: While there was no relation in girls, cigarette use appears to
      decrease body mass index and height in boys. Young girls may be less likely to
      take up cigarette smoking if tobacco control messages emphasize that cigarette
      use may not be associated with reduced weight in adolescent females.

PMID- 18346910
TI  - The impact of different measures of socioeconomic position on the relationship
      between ethnicity and health.
AB  - PURPOSE: In this study we explicitly examine the effect of using asset-based and
      conventional measures of socioeconomic position (SEP) on ethnic differences in
      health. METHODS: The survey of white (n = 227), Indian and Pakistani (n = 233),
      and African Caribbean (n = 213) adults aged 18 to 59 years living in Leeds,
      United Kingdom aimed to examine the relationship between ethnicity, health, and
      SEP. SEP variables included perceived ability to get 10,000 pounds if needed, car
      ownership, level of education, and home ownership. Health variables included self
      reported health status, presence of a long-term illness or disability, presence
      of limitations arising from a long-term illness or disability, one or more
      limitations in mobility, obesity, and being anxious, worried, or depressed.
      Logistic regression analysis was used to assess the relationship between
      ethnicity and SEP and health. Five models were run for each health variable so
      that the effects of changing the SEP measure could be ascertained. The first
      model included only ethnicity and the remaining 4 models tested the effects of
      the perceived ability to get 10,000 pounds, car ownership, level of education,
      and home ownership separately. RESULTS: The results suggest that the statistical
      inclusion of asset-based SEP measures, such as car ownership and ability to
      obtain 10,000 pounds, which reflect an individual's ability to mobilize
      resources, tend to increase ethnic differences in health, whereas more
      conventional steady-state indicators, such as education level and home ownership,
      tended to have little effect or to reduce ethnic differences in health.
      CONCLUSIONS: Overall, this study suggests that the choice of SEP measure may
      affect the conclusion of research on ethnicity and health and that choice of SEP
      measures should in turn be informed by the research problem being examined.

PMID- 18346911
TI  - Personal and family medical history correlates of rheumatoid arthritis.
AB  - PURPOSE: Patients with rheumatoid arthritis (RA) often have comorbidities related
      to immune dysfunction, however, the timing of comorbidities relative to RA
      diagnosis and treatment is not clear. We studied personal and family medical
      history correlates of incident and prevalent RA in women. METHODS: We used a
      nested case-control design including women in the Agricultural Health Study
      (AHS). Physician-confirmed cases of RA (n = 135) were matched to five controls
      each (n = 675) by birth date. We used logistic regression to examine associations
      between conditions listed in personal and family medical histories and both
      incident and prevalent RA, as estimated by odds ratios (ORs) and 95% confidence
      intervals (CIs). RESULTS: The risk of incident RA was associated with personal
      medical history of nonmelanoma skin cancer (OR = 4.4, 95% CI: 1.4-14.1), asthma
      or reactive lung disease (OR = 3.7, 95% CI: 1.3-10.5), and cataract (OR = 3.3,
      95% CI: 1.0-10.8). Personal history of herpes zoster was associated with
      prevalent RA (OR = 2.4, 95% CI: 1.2-4.8), but not with incident RA. There were no
      consistent associations between family medical history and RA. CONCLUSIONS:
      Patients with medical conditions indicating compromised immunity are at increased
      risk of developing RA. These results may indicate common pathogenesis of an
      environmental or genetic nature between such diseases.

PMID- 18346912
TI  - Detecting molecular adaptation at individual codons in the pattern recognition
      protein, lipopolysaccharide- and beta-1,3-glucan-binding protein of decapods.
AB  - Pattern recognition proteins play an important role in the innate immune response
      of invertebrates. Herein we report the evolutionary relationships among Gram
      negative bacteria binding proteins (GNBPs) that were previously identified and
      characterized from a wide array of invertebrates. Our results, together with
      those obtained in previous studies, indicate that decapod lipopolysaccharide- and
      beta-1,3-glucan binding protein (LGBP/BGBP) has retained the crucial components
      for glucanase activity, and shares a common ancestor with GNBPs, as well as with
      the glucanase proteins of a wide range of invertebrates, rather than with GNBPs
      of some arthropods. However, experimental evidence of earlier studies suggested a
      lack of glucanase activity by these proteins, thus implying that during
      evolutionary time these proteins might have lost their glucan binding protein,
      but retained their glucan binding activity. The present results have also
      revealed that although a vast majority of the decapod LGBP/BGBP codons are
      constrained to purifying selection, certain codons are shown to have a higher
      rate of nonsynonymous substitutions per nonsynonymous site (dN) than synonymous
      substitutions per synonymous site (dS), indicating these codons have evolved
      adaptively (dN/dS>1). Although purifying selection (dN/dS<1) appears to be the
      major driving force in the evolution of a vast majority of LGBP/BGBP codons in
      decapods, the findings of several hotspots for nonsynonymous substitutions in
      this protein indicate host immune selection might play an important role in
      maintaining diversity among these ecologically diversified decapod species.

PMID- 18346913
TI  - A novel MR-compatible device for providing forces to the human finger during
      functional neuroimaging studies.
AB  - Many motor learning experiments involve subjects performing a task while
      experiencing external force perturbations. However, it is difficult to transfer
      these tasks to functional magnetic resonance imaging (fMRI) studies, and much of
      the technology that currently exists to facilitate this is expensive to produce
      and difficult to use. Here, we report on the design and construction of a novel
      device (the 'force coil') that is simple and inexpensive, and that uses the
      static magnetic field inside the scanner to provide forces to the human finger.
      The coil incorporates a potentiometer in the base to allow the recording of
      angular position. To test whether the magnetic field generated by the current
      flowing through the coil would interfere with the functional images collected, we
      compared images from a phantom during the use of the coil at arm's length in a 7T
      magnet. There was no noticeable interference from the coil at the levels of
      current used in this experiment, which produced about 10 N of force in a 7T
      scanner. In conclusion, the force coil is a cheap, easy to operate device which
      provides forces to the finger inside the scanner without affecting image quality.
      Designs based on this principle are likely to prove useful in studies of motor
      learning using fMRI.

PMID- 18346914
TI  - Genetic and morphological evidence for substantial hidden biodiversity in a
      freshwater crayfish species complex.
AB  - North America is a center of biodiversity for freshwater crayfish, with >300
      described species, mostly in the family Cambaridae. However, the phylogenetic and
      phylogeographic relationships among these taxa are poorly understood, despite
      their ubiquitous occurrence in North American freshwater habitats. Here, we
      target the geographically widespread Orconectesvirilis and its sister taxa for
      genetic and morphological investigation. We used sequence data from two
      mitochondrial genes (16S rRNA and cytochrome oxidase I) and from one nuclear gene
      (glyceraldehyde-3-phosphate dehydrogenase), as well as morphological data from
      the male gonopod, to gain insights into phylogenetic relationships among
      individuals collected in the northeastern United States, where this taxon is
      considered to be invasive, and from Kansas. Our data reveal evidence for three
      cryptic species in our collections, in addition to O.virilis sensu stricto; all
      four clades are separated by both mitochondrial and nuclear sequence data. In
      addition, two of the newly discovered species, O.sp. nov. A and O.sp. nov. B, are
      distinguishable from O.virilis by significant differences in gonopod morphology
      (no data on gonopod morphology were available for O.sp. nov. C). O.sp. nov. A was
      collected at numerous sites in Massachusetts; additional sampling is required to
      determine if this species is native to New England. Two other taxa, O.sp. nov. B
      and O.sp. nov. C, were both collected from sites in eastern Kansas, and
      historically have probably been considered to be O.nais. In summary, this
      investigation indicates that this species complex may harbor a great deal of
      unknown biodiversity over the rest of its described range, and suggests that
      further attention to the phylogenetics and phylogeography of North American
      crayfishes may yield interesting insights into the evolution of biodiversity.

PMID- 18346915
TI  - Amelogenin, the major protein of tooth enamel: a new phylogenetic marker for
      ordinal mammal relationships.

PMID- 18346916
TI  - Geography and host biogeography matter for understanding the phylogeography of a
      parasite.
AB  - The co-evolution between hosts and parasites has long been recognized as a
      fundamental driver of macro-evolutionary patterns of diversification. The effect
      of co-differentiation on parasite diversification is, however, often confounded
      by underlying geographic patterns of host distribution. In order to disentangle
      the confounding effects of allopatric versus host speciation, the mitochondrial
      cytochrome b (cyt b) gene was sequenced in seventy individuals of the parasitic
      nematode genus Heligmosomoides sampled in the six Apodemus mice species common in
      the western Palearctic region. The nuclear internal transcribed spacers (ITS) 1
      and 2 were also sequenced in fifteen parasites to confirm the mitochondrial data.
      All lineages differentiated according to a geographic pattern and independently
      from the sampled host species. This suggests that host speciation did not involve
      concurrent parasite speciation. However, the geographic distribution range of
      some parasite lineages mirrors that of A. sylvaticus lineages in SW Europe, and
      that of A. flavicollis lineages in the Balkans and in the Middle East. Thus,
      regional co-differentiation likely occurred between the parasite and the two
      sister Apodemus hosts in different parts of their distribution range. We suggest
      that differences in regional abundances of A. sylvaticus and A. flavicollis are
      responsible for generating this pattern of regional co-differentiation. This
      study highlights the importance of integrating both geography and biogeographic
      information from potential hosts to better understand their parasite
      phylogeography.

PMID- 18346917
TI  - Reticulate evolution in Thuja inferred from multiple gene sequences: implications
      for the study of biogeographical disjunction between eastern Asia and North
      America.
AB  - The eastern Asia-North America disjunction is one of the most interesting
      biogeographical patterns, but its formation is still in much debate. Here
      nucleotide sequences of five cpDNA regions, nrDNA ITS and two low-copy nuclear
      genes (LEAFY, 4CL) were employed to reconstruct the phylogeny and to explore the
      historical biogeography of Thuja, a typical eastern Asia-North America disjunct
      genus. High topological discordance was observed between chloroplast and nuclear
      gene trees, even between different nuclear gene trees, suggesting that Thuja
      could have a reticulate evolutionary history due to multiple interspecific
      hybridization events. The eastern Asian species Thuja koraiensis might have
      obtained its chloroplast genome from the eastern North American species T.
      occidentalis by chloroplast capture, while the western North American species T.
      plicata is very likely to have inherited a recombinant cpDNA. Based on the
      phylogenetic analysis of multiple genes, DIVA-reconstruction of the distribution
      history, molecular clock estimation and fossil data, we inferred that Thuja could
      have originated from the high-latitude areas of North America in the Paleocene or
      earlier with subsequent expansion into eastern Asia through the Bering Land
      Bridge. The two eastern Asia species T. standishii and T. sutchuenensis have a
      sister relationship, and their split could have occurred in the Oligocene or
      early Miocene. In the present study, the selection of molecular markers in
      biogeographic studies was also discussed. Since most previous studies on the
      eastern Asia and North America disjunction are based on uniparentally inherited
      cpDNA and (or) directly sequenced nrDNA ITS data, the historical reticulate
      evolution in the studied groups might have been underestimated. Therefore, we
      suggest that multiple genes from different genomes, especially low-copy nuclear
      genes, be used in this research area in the future.

PMID- 18346918
TI  - BCL6 represses CHEK1 and suppresses DNA damage pathways in normal and malignant B
      cells.
AB  - BCL6 is a transcriptional repressor protein that is expressed in a
      developmentally regulated fashion during B-cell maturation. Specifically, BCL6 is
      required for formation of germinal centers in response to T-cell dependent
      antigen activation. Germinal center B-cells feature the ability to tolerate rapid
      proliferation and simultaneous genetic recombination. Genetic lesions that cause
      constitutive expression of BCL6 are commonly associated with diffuse large B-cell
      lymphomas (DLBCL). Recent studies show that BCL6 contributes to the germinal
      center phenotype by directly repressing genes involved in sensing or responding
      to DNA damage including ATR, TP53 and CDKN1A. The CHEK1 protein is activated
      through phosphorylation by the ATR kinase domain in response to DNA damage.
      Activated CHEK1 can phosphorylate and modulate the activity a number of proteins
      including p53, providing a link between ATR sensing of DNA damage and p53
      checkpoint activity. Herein we show that BCL6 can directly bind to a DNA
      consensus element in the CHEK1 promoter and repress its expression in normal and
      malignant B-cells. DLBCL cells can be killed by a specific BCL6 peptide inhibitor
      (BPI) that interferes with corepressor binding to the BCL6 BTB domain. BPI could
      reactivate CHEK1 in DLBCL cells, suggesting that its induction might contribute
      to BPI anti-lymphoma effects. Therefore, BCL6 can suppress multiple genes
      involved in a common pathway sensing, transducing and responding to genotoxic
      stress.

PMID- 18346919
TI  - Speciation in fungi.
AB  - In this review on fungal speciation, we first contrast the issues of species
      definition and species criteria and show that by distinguishing the two concepts
      the approaches to studying the speciation can be clarified. We then review recent
      developments in the understanding of modes of speciation in fungi. Allopatric
      speciation raises no theoretical problem and numerous fungal examples exist from
      nature. We explain the theoretical difficulties raised by sympatric speciation,
      review the most recent models, and provide some natural examples consistent with
      speciation in sympatry. We describe the nature of prezygotic and postzygotic
      reproductive isolation in fungi and examine their evolution as functions of
      temporal and of the geographical distributions. We then review the theory and
      evidence for roles of cospeciation, host shifts, hybridization, karyotypic
      rearrangement, and epigenetic mechanisms in fungal speciation. Finally, we review
      the available data on the genetics of speciation in fungi and address the issue
      of speciation in asexual species.

PMID- 18346920
TI  - Enhanced placental cholesterol efflux by fetal HDL in Smith-Lemli-Opitz syndrome.
AB  - Previous studies from this laboratory have shown that maternal-derived
      cholesterol can be effluxed from trophoblasts to fetal HDL and plasma. We had the
      opportunity to study for the first time the ability of HDL and plasma from a
      fetus with the Smith-Lemli-Opitz syndrome (SLOS) to efflux cholesterol from
      trophoblasts. It was unclear whether cholesterol could be effluxed to fetuses
      with SLOS since lipoprotein levels are often very low. To answer this question,
      cord blood was collected from the placentas of an SLOS fetus and unaffected
      fetuses just after delivery. Plasma cholesterol concentrations were very low in
      the affected fetus; cholesterol, 7-dehydrocholesterol, and 8-dehydocholesterol
      concentrations were 14.1, 4.5, and 5.2 mg/dl, respectively. The HDL from the
      fetal SLOS effluxed approximately 50% more cholesterol from a trophoblast cell
      line, were smaller in size, and had a lower cholesterol to phospholipid ratio as
      compared to HDL from unaffected fetuses or adults. Plasma from the SLOS fetus
      effluxed cholesterol to a similar percentage as unaffected fetal plasma or adult
      plasma, possibly due to fewer HDL particles as demonstrated in previous SLOS
      patients. These novel data demonstrate that the cholesterol-deficient SLOS fetus
      is able to obtain cholesterol from trophoblasts at a time when cholesterol is
      playing a critical role in development, and has implications for design of
      treatments for cholesterol deficiency syndromes as well as understanding of
      prenatal cholesterol transport in humans.

PMID- 18346921
TI  - Dependence of reversibility and progression of mouse neuronopathic Gaucher
      disease on acid beta-glucosidase residual activity levels.
AB  - Genetic and chemically induced neuronopathic mouse models of Gaucher disease were
      developed to facilitate understanding of the reversibility and/or progression of
      CNS involvement. The lethality of the skin permeability barrier defect of the
      complete gene knock out [gba, (glucocerebrosidase) GCase] was avoided by
      conditional reactivation of a low activity allele (D409H) in keratinocytes (kn
      9H). In kn-9H mice, progressive CNS disease and massive glucosylceramide storage
      in tissues led to death from CNS involvement by the age of 14 days. Conduritol B
      epoxide (CBE, a covalent inhibitor of GCase) treatment (for 8-12 days) of wild
      type, D409H, D409V or V394L homozygotes recapitulated the CNS phenotype of the kn
      9H mice with seizures, tail arching, shaking, tremor, quadriparesis, extensive
      neuronal degeneration loss and apoptosis, and death by the age of 14 days. Minor
      CNS abnormalities occurred after daily CBE injections of 100 mg/kg/day for 6
      doses, but neuronal degeneration was progressive and glucosylceramide storage
      persisted in D409V homozygotes in the 2 to 5 months after CBE cessation; wild
      type and D409H mice had persistent neurological damage without progression. The
      persistent CNS deterioration, histologic abnormalities, and glucosylceramide
      storage in the CBE-treated D409V mice revealed a threshold level of GCase
      activity necessary for the prevention of progression of CNS involvement.

PMID- 18346922
TI  - An unusual case of Corynebacterium striatum endocarditis and a review of the
      literature.

PMID- 18346923
TI  - [Tuberculosis dactylis: a case report].
AB  - INTRODUCTION: Tuberculosis dactylis is exceptional. We report one case in an 11
      years old girl. OBSERVATION: N.D., 11 years old, was admitted for a right hand
      second finger tumour evolving since six months and linked to a trauma. Clinical
      examination founded a painful fusiform of the right second finger with limited
      movements of the finger. The hand radiography showed a second phalange osteitis
      of the finger without periosteitis reaction. The sedimentation rate was
      accelerated to 130 mm at the first hour. The intracutaneous reaction with
      tuberculin was positive to 19 mm. In her preceding, her mother would have
      suffered from pulmonary tuberculosis two years before incompletely treated during
      eight months. Histological examination showed a caseous necrosis and an
      epithelial giant cellular follicle. A twelve months antituberculosis
      polychimiotherapy permitted a healing without sequelae. DISCUSSION: Tuberculosis
      dactylis has to be evoked with epidemiological, clinical, radiological and
      immunological arguments. The antituberculosis treatment permitted to do the
      retrospective diagnosis and to get a healing.

PMID- 18346924
TI  - A case of death from the explosion of a 66mm M72 High Explosive Anti-Tank rocket.
AB  - A 53-year-old male died from an explosion of a 66 mm M72 High Explosive Anti-Tank
      (HEAT) rocket. He had collected various cast-off military weapons and was selling
      them. There were numerous explosive injuries on the anterior side of the body,
      thus especially bilateral hands, left toe and right knee were severely crushed
      and fractured. The location and severity of the injuries suggest that he was down
      on his left knee and was manipulating the weapon with both hands at the moment of
      detonation. We consider that 66 mm M72 HEAT rocket accidentally detonated during
      his handling. Very rarely are civilians killed by a military weapon, except
      during wartime. Appropriate investigation of various explosive injuries provide
      not only evidence of the cause of death, but also the position and posture of the
      body.

PMID- 18346925
TI  - Subcortical neurofibrillary tangles and argyrophilic grains in a case of familial
      frontotemporal dementia with parkinsonism.
AB  - A case of familial frontotemporal dementia with parkinsonism (FTDP) similar to
      progressive supranuclear palsy (PSP) was reported. A 58-year-old man developed
      personality change followed by parkinsonism and dementia. Three family members
      showed similar symptoms. Cerebral atrophy was marked on the anterior
      frontotemporal lobes. The substantia nigra, hippocampus, peri-aqueductal gray
      matter and pontine nucleus were affected with globose neurofibrillary tangles
      (NFT) and glial tangles. Argyrophilic grains were distributed in the CA1-CA2.
      NFT, glial tangles and argyrophilic grains expressed four-repeat microtubule
      associated protein tau (MAPT). MAPT gene had no mutation. Familial occurrence of
      FTDP with PSP-like tauopathy is rare.

PMID- 18346926
TI  - Handedness as a predictor of side of onset of Parkinson's disease.
AB  - The prevalence and predictive factors of asymmetry in Parkinson's disease have
      hardly been investigated. The aim of this study was to determine the rate of
      asymmetric features in patients with Parkinson's disease. The study group
      consisted of 307 patients with idiopathic Parkinson's disease. The dominant hand
      was recorded in each case, and right-left differences in tremor, bradykinesia,
      and rigidity was defined as a difference of more than 4 points on the Unified
      Parkinson Disease Rating Scale. Asymmetric presentation was noted in 260 patients
      [84.7%]. The initial symptoms appeared on the right side in 47% of the right
      handed patients [on the left side in 38% of the right-handed patients], and on
      the left side in 52% of the left-handed patients [on the right side in 36% of
      them] [p=0.06]. In conclusion, Parkinson's disease appears to be characterized by
      asymmetry of symptoms. There was a trend toward symptoms onset on the dominant
      side.

PMID- 18346927
TI  - The transactivation domain of heterogeneous nuclear ribonucleoprotein K overlaps
      its nuclear shuttling domain.
AB  - The heterogeneous nuclear ribonucleoprotein K (hnRNP K) protein is a versatile
      molecule that interacts with RNA, DNA, and a number of transcription factors,
      implicating it in transcription, splicing, and translation processes. The
      underlying mechanism of transcription stimulation by hnRNP K is not well
      understood. To explore the possibility of a putative transactivation activity of
      hnRNP K, we produced constructs in which the yeast Gal4 DNA-binding domain was
      fused to various hnRNP K fragments in one-hybrid mammalian cells. Our results
      reveal that the K nuclear shuttling (KNS) domain, a well-known signal for nuclear
      import and export, is also responsible for the transactivation activity of hnRNP
      K protein. Importin alpha and beta proteins are involved in the regulation of the
      transactivation activity of the KNS domain via their competition for the nuclear
      pore complex. Site-directed mutants of serine residue 353 to alanine or aspartic
      acid or a series of truncated mutants of amino acids 338-363 of hnRNP K suggest
      the transactivation activity of KNS is primarily dependent on its amino acid
      composition and intact structure. Our results suggest that endogenous p53 is not
      required for the activity of the KNS domain, but that overexpression of exogenous
      p53 might affect its activity in a dose-dependent manner. We thus demonstrate the
      existence of a strong transactivation domain in hnRNP K and define the regulatory
      mechanism involved in its protein-protein interaction within the KNS domain in
      cells.

PMID- 18346928
TI  - Relevance of Arg457 for the nucleotide affinity of Saccharomyces cerevisiae
      phosphoenolpyruvate carboxykinase.
AB  - Phosphoenolpyruvate carboxykinases catalyze one of the first steps in the
      biosynthesis of glucose and depending on the enzyme origin, preferentially use
      adenine or guanine nucleotides as substrates. The Saccharomyces cerevisiae enzyme
      has a marked preference for ADP (or ATP) over other nucleotides. Homology models
      of the enzyme in complex with ADP or ATP show that the guanidinium group of
      Arg457 is close to the adenine base, suggesting that this group might be involved
      in the stabilization of the nucleotide substrate. To evaluate this we have
      performed the mutation Arg457Met, replacing the positively charged guanidinium
      group by a neutral residue. The mutated enzyme retained the structural
      characteristics of the wild-type protein. Fluorescence titration experiments
      showed that mutation causes a loss of 1.7 kcal mol(-1) in the binding affinity of
      the enzyme for ADPMn. Similarly, kinetic analyses of the mutated enzyme showed 50
      fold increase in K(m) for ADPMn, with minor alterations in the other kinetic
      parameters. These results show that Arg457 is an important factor for nucleotide
      binding by S. cerevisiae PEP carboxykinase.

PMID- 18346929
TI  - Activation of epidermal growth factor receptor by metal-ligand complexes
      decreases levels of extracellular amyloid beta peptide.
AB  - The epidermal growth factor receptor is a receptor tyrosine kinase expressed in a
      range of tissues and cell-types. Activation of the epidermal growth factor
      receptor by a number of ligands induces downstream signalling that modulates
      critical cell functions including growth, survival and differentiation. Abnormal
      epidermal growth factor receptor expression and activation is also involved in a
      number of cancers. In addition to its cognate ligands, the epidermal growth
      factor receptor can be activated by metals such as zinc (Zn) and copper (Cu). Due
      to the important role of these metals in a number of diseases including
      neurodegenerative disorders, therapeutic approaches are being developed based on
      the use of lipid permeable metal-complexing molecules. While these agents are
      showing promising results in animal models and clinical trials, little is known
      about the effects of metal-ligand complexes on cell signalling pathways. In this
      study, we investigated the effects of clioquinol (CQ)-metal complexes on
      activation of epidermal growth factor receptor. We show here that CQ-Cu complexes
      induced potent epidermal growth factor receptor phosphorylation resulting in
      downstream activation of extracellular signal-regulated kinase. Similar levels of
      epidermal growth factor receptor activation were observed with alternative lipid
      permeable metal-ligands including neocuproine and pyrrolidine dithiocarbamate. We
      found that CQ-Cu complexes induced a significant reduction in the level of
      extracellular Abeta1-40 in cell culture. Inhibition of epidermal growth factor
      receptor activation by PD153035 blocked extracellular signal-regulated kinase
      phosphorylation and restored Abeta1-40 levels. Activation of the epidermal growth
      factor receptor by CQ-Cu was mediated through up-regulation of src kinase
      activity by a cognate ligand-independent process involving membrane integrins.
      These findings provide the first evidence that metal-ligand complexes can
      activate the epidermal growth factor receptor with potentially neuroprotective
      effects.

PMID- 18346930
TI  - Involvement of CCAAT/enhancer binding protein-beta (C/EBPbeta) in epigenetic
      regulation of mouse methionine adenosyltransferase 1A gene expression.
AB  - Methionine adenosyltransferase (MAT) catalyzes the synthesis of S
      adenosylmethionine, the main methyl donor in cellular transmethylation reactions
      and the aminopropyl moiety in polyamine biosynthesis. In mammals, two different
      genes, MAT1A and MAT2A, encode catalytic polypeptides of liver-specific MAT I/III
      and ubiquitous MAT II, respectively. Reverse transcription-polymerase chain
      reaction showed that MAT1A gene expression was at a detectable level in embryonic
      day 14 mouse fetal liver and subsequently increased. Bisulfite genomic sequencing
      indicated that the methylation status of 10CpG sites in the MAT1A promoter
      proximal region was appreciably correlated with the gene expression in mouse
      developing liver and in adult hepatic cells; hepatic stellate cells and
      hepatocytes. When mouse hepatoma-derived Hepa-1 cells showing extremely low
      expression of MAT1A gene were treated with 5-aza-2'-deoxycytidine and
      trichostatin A, MAT1A gene expression was enhanced. In addition, in vitro
      methylation of the MAT1A promoter region suppressed the MAT1A promoter activity
      in reporter assay. Next, we performed electrophoretic mobility shift assay and
      found that the transcriptional factor CCAAT/enhancer binding protein-beta
      (C/EBPbeta) specifically binds to a putative binding site of C/EBPbeta in the
      MAT1A promoter. Suppression of C/EBPbeta expression by short hairpin RNA
      decreased the MAT1A promoter activity and MAT1A gene expression, and inhibition
      of C/EBPbeta binding to MAT1A by site-directed mutagenesis also showed similar
      results. Western blot analysis and chromatin immunoprecipitation assay indicated
      that C/EBPbeta binding is dependent on DNA methylation status. Based on these
      findings, we conclude that C/EBPbeta plays an important role in epigenetic
      regulation of the mature hepatic gene MAT1A.

PMID- 18346931
TI  - Automatic initialization of an active shape model of the prostate.
AB  - In this work is reported a new method for automatic segmentation of the boundary
      of the prostate, in transurethral ultrasound images. The scheme is based on a
      robust automatic initialization of an active shape model (ASM) of the prostate,
      which is subsequently fitted to the boundary of the gland. The initialization of
      the ASM is based on pixel classification to estimate the prostate region in an
      ultrasound image, followed by automatic adjustment - using a multipopulation
      genetic algorithm (MPGA) - of the initial pose of the ASM to the binary image
      produced by the classifier. The initial pose is next adjusted to the gray level
      ultrasound image, using the MPGA. After automatic initialization, the ASM is
      adjusted to the gray level ultrasound image to produce the final prostate
      contour. The method provides fast and robust segmentation of the prostate
      boundary. Validation results on 22 ultrasound images are reported with 1.74 mm of
      mean boundary error and an estimated processing time of 66 per image. Our
      automatic initialization method can be applied with the ASMs of different organs
      in various imaging modalities.

PMID- 18346932
TI  - Microsatellite mutations in the offspring of irradiated parents 19 years after
      the Cesium-137 accident.
AB  - In September of 1987, a radiotherapy unit containing 50.9 TBq of Cs(137)Cl was
      removed from an abandoned radiotherapy clinic. This unit was subsequently
      disassembled leading to the most serious radiological accident yet to occur in
      the Western hemisphere. This event provides an opportunity to assess the genetic
      effects of ionizing radiation. We surveyed genetic variation of 12 microsatellite
      loci in 10 families of exposed individuals and their offspring and also in non
      exposed families from the same area of Goias state. We found an increase in the
      number of new alleles in the offspring of the exposed individuals. The mutation
      rate was found to be higher in the exposed families compared to the control
      group. These results indicated that exposure to ionizing radiation can be
      detected in offspring of exposed individuals and also suggest that the elevated
      microsatellite mutation rate can be attributed to radioactive exposure.

PMID- 18346933
TI  - Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt:
      possibilities for prevention.
AB  - The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a
      doubling in the incidence rate in the past 10 years. This has been attributed to
      several biological (e.g. hepatitis B and C virus infection) and environmental
      factors (e.g. aflatoxin, AF). Other factors such as cigarette smoking,
      occupational exposure to chemicals such as pesticides, and endemic infections in
      the community, such as schistosomiasis, may have additional roles in the etiology
      or progression of the disease. Estimates of the burden of cancer caused by these
      factors provide an opportunity for prevention. Previously, there was strong
      evidence that hepatitis B virus (HBV) was the major cause of HCC in Egypt, but
      more recently HCV has become the predominant factor associated with the more
      recent epidemic of HCC. It has been well documented that Egypt has one of the
      highest prevalence rates of HCV infection in the world. The natural history of
      HCV infection and disease progression, however, are influenced by additional
      factors such as duration of infection, age at infection, sex, co-infection with
      HBV, the level of HCV viraemia and its genotype. The role of exposure to
      aflatoxins and development of HCC in Egypt was historically less clear.
      Nevertheless, recent food sampling surveys and population-based studies indicated
      that exposure to aflatoxins in Egypt may have been underestimated in the past.
      Recent results indicated that both local and imported samples were positive for
      aflatoxin B1 (AFB1, 17.5% and 20%, respectively), with concentrations ranging
      from 3 to 25 microg/kg. The level of AFB1 was dependent on the area of collection
      as well as the season of the year. In a population-based study, the level and
      frequency of aflatoxin M1 (AFM1, a major metabolite of aflatoxin B1 excreted in
      breast milk) was assessed as a biomarker of maternal exposure. The samples were
      collected from a selected group of 388 Egyptian lactating mothers during May
      September 2003. Non-working status, obesity, high corn oil consumption, and the
      number of offspring contributed to the variability in occurrence of AFM1 in
      breast milk. Prevention and intervention approaches directed to risk factors of
      HCC can play a critical role in its prevention. In the case of HCV infection a
      prevention programme can be achieved by changing personal behaviors and/or
      cultural habits which are risk factors for HCV transmission, such as injection
      with contaminated syringes, blood transfusion, surgical operations, venous
      catheterization, use of common syringes, dental treatment and circumcision at
      home. Prevention of exposure to aflatoxins can be achieved either at community
      (via good agriculture practices) or individual levels (treatment or dietary
      interventions). In conclusion, due to the alarming increase in the incidence of
      HCC in Egypt, there is a need to further investigate the contribution of these
      emerging risk factors to the development of HCC in Egypt. This may enable us to
      determine the susceptibility to HCC among high-risk groups and to provide these
      individuals with effective measures for early prevention or intervention.

PMID- 18346934
TI  - Preferential solvation of acridine in binary mixtures.
AB  - Preferential solvation studies of acridine have been investigated using optical
      absorption technique. The preferential solvation parameter shows that in dimethyl
      formamide (DMF)+ethanol mixture, the acridine is preferentially solvated by
      ethanol in DMF rich region and by DMF in ethanol rich region. In the case of
      DMF+Carbon tetrachloride mixture acridine is preferentially solvated by DMF.

PMID- 18346935
TI  - Serological patterns and temporal trends of HTLV-1/2 infection in high-risk
      populations attending Public Health Units in Sao Paulo, Brazil.
AB  - BACKGROUND: HTLV-1/2 diagnosis in high-risk populations from Sao Paulo, Brazil
      has been problematic due a high proportion of seroindeterminate results.
      OBJECTIVES: To confirm and extend previous findings regarding HTLV-1/2 diagnosis
      in this geographic area. STUDY DESIGN: Sera from 2312 patients were tested for
      HTLV-1/2 antibodies using enzyme immunoassay (EIA) and Western blot (WB)
      analysis. Patients were from AIDS Reference Centers (Group I; 1393 patients) and
      HTLV out-patient clinics (Group II; 919 patients). Results were analyzed
      according to patients' age, gender, and clinic type. RESULTS: HTLV-1 and HTLV-2
      were detected in both groups. Among seropositive females, HTLV-2 was slightly
      more common in Group I (54.5%), while HTLV-1 prevailed in Group II (73.9%). Males
      from Group II had a higher percentage of HTLV-seroindeterminate results. No
      correlation between HTLV serological results and age was detected. Temporal
      analyses disclosed a high number of HTLV-seroindeterminate samples, and a large
      spectrum of indeterminate WB profiles. GD21 and/or rgp46-II bands were detected
      in 34.6% of sera from Group I, and a p24 or p19 band was detected in 35.3% of
      sera from Group II. CONCLUSIONS: High rates of HTLV-indeterminate serological
      patterns during temporal analyses were confirmed in high-risk populations from
      Sao Paulo, Brazil.

PMID- 18346936
TI  - Interfering with extracellular matrix degradation to blunt inflammation.
AB  - Chemoattractant properties of matrix proteins, like collagen and elastin, for
      neutrophils and monocytes in vitro have long been recognized. This activity often
      resides in fragments of these proteins. These peptides may play a role in
      diseases of the lung matrix, such as chronic obstructive pulmonary disease.
      Recent advances include the elucidation of the structure of chemotactic collagen
      fragments and the demonstration that their activity may reside in a structural
      relatedness to CXC chemokines. Collagen and elastin fragments have been
      demonstrated to have a role in in vivo lung pathophysiology and have been
      quantified in patients with chronic lung diseases where they may activate
      autoimmune pathways. Elucidation of these pathways may provide novel biomarkers
      and therapeutic targets for chronic lung diseases.

PMID- 18346937
TI  - Stored packed red blood cells contain a procoagulant phospholipid reducible by
      leukodepletion filters and washing.
AB  - BACKGROUND: Ageing RBC gradually increase the exposure of phosphatidylserine (PS)
      on their surface, due to loss of membrane asymmetry. PS expression on red cells
      is not normally a significant factor in the hemostatic process, because aged RBC
      are rapidly cleared from the circulation. We propose that the presence of many
      altered red cells during massive transfusion can lead to increased procoagulant
      activity similar to what is seen in disease states where it is known to play a
      pathophysiologic role in microvascular disease. STUDY DESIGN AND METHODS:
      Procoagulant activity of phospholipid generated during storage of PRBC was
      evaluated using PRBC's as the only source of phospholipid in the determination of
      modified Russell's viper venom times of 10 PRBC units in which half of each unit
      was left unfiltered and half of each unit filtered. Florescent labeled annexin V
      binding by PRBC was also assessed by flow cytometry over time in storage. The
      effect of washing and filtration on these parameters was also determined.
      RESULTS: As time of storage increased, the Russell's viper venom time of both the
      unfiltered and filtered units shortened (p<0.01). There was a significant
      lengthening of the Russell's viper venom time at all time points measured when
      unfiltered units were compared to filtered units (p<0.01). In both unfiltered and
      filtered units, with increased length of storage, there was a gradual increase in
      the percentage of cells or particles binding annexin V (p<0.01). Filtration
      resulted in a significant reduction in the percentage of cells or particles
      binding annexin V at all time points measured (p<0.01). The effect of washing of
      PRBC units on the RVVT was assessed for unfiltered and filtered units on day 42.
      Washing resulted in a significant reduction of the RVVT in both unfiltered and
      filtered groups (p<0.01). CONCLUSIONS: Levels of annexin V binding and
      procoagulant phospholipid activity similar to levels seen in disease states
      associated with significant vasoocclusive pathophysiology were found toward the
      end of the storage period of PRBC units. It was possible to reduce both of these
      parameters by leukodepletion at collection, and with washing of PRBC at the end
      of storage. Filtration at collection resulted in a 67% increase in RVVT over
      unfiltered units by day 42 of storage. On day 42 of storage, washing of filtered
      units resulted in a 21% increase in RVVT, and washing of unfiltered units
      resulted in a 34% increase in RVVT. The effects seen with filtration and washing
      were additive suggesting that in spite of filtration at collection, deterioration
      of cells continues based on age since further removal of phospholipid can be
      induced with washing of filtered units on day 42.

PMID- 18346938
TI  - Amelioration of collagen-induced arthritis by human recombinant soluble
      FcgammaRIIb.
AB  - Immune complex (IC) binding to Fc gamma receptors (FcgammaRs) is central for
      inflammatory reactions seen in autoimmune diseases. Consequently, a therapeutic
      agent with a possibility to interfere with binding of pathogenic IC to FcgammaRs
      would be valuable in autoimmune disorders such as rheumatoid arthritis (RA). Here
      we have explored the therapeutic effect of a recombinant soluble human
      FcgammaRIIb (sFcgammaRIIb) protein in collagen-induced arthritis (CIA). In vitro
      studies of the sFcgammaRIIb demonstrated binding to mouse IgG, suggesting that
      sFcgammaRIIb can absorb pathogenic IgG anti-collagen type II (CII) IC in vivo.
      Hence, administration of sFcgammaRIIb significantly reduced CIA severity compared
      to control treated mice. The sFcgammaRIIb treated mice had significantly less IgG
      anti-CII antibodies in serum and lower mRNA levels of inflammatory cytokines
      compared to control mice. In conclusion, sFcgammaRIIb treatment ameliorates CIA
      by reducing IC-stimulated inflammation and joint swelling. This suggests that
      recombinant sFcgammaRIIb may be useful as therapeutic agent in RA.

PMID- 18346940
TI  - Motor and mental development of infants exposed to antiepileptic drugs in utero.
AB  - We prospectively evaluated the mental (MeDQ) and motor (MoDQ) developmental
      quotients of 395 (67.5% of the eligible) infants of mothers with epilepsy (IME)
      (mean age: 15 months) enrolled in the Kerala Registry of Epilepsy and Pregnancy
      between 1998 and 2004. The same developmental pediatricians, blinded to
      antiepileptic drug (AED) exposure, evaluated the children using the Indian
      adaptation of the Bayley Scale of Infant Development: Their mean MeDQ was 89.1+/
      29.9 and mean MoDQ was 90.7+/-26.9. The MeDQ and MoDQ were impaired (<84) for 150
      (37.6%) and 133 (33.5%) IME, respectively. Maternal age, type of epilepsy,
      seizure frequency, or use of folic acid did not correlate with the mean MeDQ or
      MoDQ. Maternal education was significantly correlated with the MoDQ, but not with
      the MeDQ, of the infants. Infants not exposed to AEDs (n=32) had a higher MeDQ
      (mean: 92.3, 95% CI: 81.4-103.2) and MoDQ (mean 94.7; 95% CI 84.9-104.5) than
      those exposed to AEDs (MeDQ--mean: 88.6, 95% CI: 85.5-91.6; MoDQ--mean: 90.0, 95%
      CI: 87.3-92.8). Those exposed to polytherapy had significantly lower
      developmental quotients than those exposed to monotherapy. Cumulative AED scores
      during pregnancy had an inverse relationship with developmental quotients. On
      multiple regression analysis, polytherapy was a stronger predictor of lower
      developmental quotients than dosage. Compared with carbamazepine monotherapy,
      valproate monotherapy was associated with significantly lower MeDQ and MoDQ in
      IME (93.1 and 95 vs 86.9 and 86.1), but the differences between other AEDs were
      not significant for IME exposed to valproate monotherapy. A limitation of the
      study is that the influence of maternal intelligence on developmental quotients
      was not evaluated.

PMID- 18346939
TI  - The role of sex steroids in catamenial epilepsy and premenstrual dysphoric
      disorder: implications for diagnosis and treatment.
AB  - Despite our understanding of hormonal influences on central nervous system (CNS)
      function, there is still much to learn about the pathogenesis of menstrual cycle
      linked disorders. A growing literature suggests that the influence of sex
      steroids on neurological and psychiatric disorders is in part mediated by an
      aberrant CNS response to neuroactive steroids. Although sex steroids such as
      estradiol, progesterone, and the progesterone derivative allopregnanolone (ALLO)
      influence numerous neurotransmitter systems, it is their potent effect on the
      brain's primary inhibitory and excitatory neurotransmitters gamma-aminobutyric
      acid (GABA) and glutamate that links the study of premenstrual dysphoric disorder
      (PMDD) and catamenial epilepsy (CE). After providing an overview of these
      menstrual cycle-linked disorders, this article focuses on the preclinical and
      clinical research investigating the role of estradiol and progesterone (via ALLO)
      in the etiology of PMDD and CE. Through exploration of the phenomenological and
      neurobiological overlap between CE and PMDD, we aim to highlight areas for future
      research and development of treatments for menstrual cycle-linked
      neuropsychiatric disorders.

PMID- 18346941
TI  - Self-proxy agreement and correlates of health-related quality of life in young
      adults with epilepsy and mild intellectual disabilities.
AB  - This study investigated health-related quality of life (HRQOL) in young adults
      with epilepsy and intellectual disabilities. First, agreement between self
      reports and proxy reports of HRQOL was examined. Second, medical and
      psychological contributions to HRQOL were explored. Thirty-six patients were
      interviewed using the Quality of Life in Epilepsy inventory (QOLIE-31), the
      Hospital Anxiety and Depression Scale, and the Neuroticism and Extraversion
      scales of the NEO Five-Factor Inventory. Medical data were taken from files.
      Professional caregivers completed rephrased QOLIE-31-questionnaires. The
      perspectives on HRQOL differed systematically: Caregivers underrated their
      clients' HRQOL on average. Few correlations with medical characteristics emerged,
      whereas all psychological variables were strongly related to HRQOL. Neuroticism,
      Age at Disability Onset, and their interaction explained 71% of the HRQOL
      variance. Results indicate that proxy reports do not provide valid substitutes
      for most of the self-reported HRQOL subscales. Psychological treatment of
      negative affectivity and after critical life events in adolescence may improve
      HRQOL in young adults with epilepsy and mild intellectual disabilities.

PMID- 18346942
TI  - Using the Internet to search for cancer clinical trials: a comparative audit of
      clinical trial search tools.
AB  - Advancing the clinical trial research process to improve cancer treatment
      necessitates helping people with cancer identify and enroll in studies, and
      researchers are using the power of the Internet to facilitate this process. This
      study used a content analysis of online cancer clinical trial search tools to
      understand what people with cancer might encounter. The content analysis revealed
      that clinical trial search tools were easy to identify using a popular search
      engine, but their functionality and content varied greatly. Most required that
      users be fairly knowledgeable about their medical condition and sophisticated in
      their web navigation skills. The ability to search by a specific health condition
      or type of cancer was the most common search strategy. The more complex tools
      required that users input detailed information about their personal medical
      history and have knowledge of specific clinical trial terminology. Search tools,
      however, only occasionally advised users to consult their doctors regarding
      clinical trial decision-making. This, along with the complexity of the tools
      suggests that online search tools may not adequately facilitate the clinical
      trial recruitment process. Findings from this analysis can be used as a framework
      from which to systematically examine actual consumer experience with online
      clinical trial search tools.

PMID- 18346944
TI  - The role of the environment in the evolutionary ecology of host parasite
      interactions: meeting report, Paris, 5th December, 2007.

PMID- 18346943
TI  - Transcriptional profiling of Wnt4 mutant mouse kidneys identifies genes expressed
      during nephron formation.
AB  - The mature nephron forms from a simple epithelial vesicle into an elaborate
      structure with distinct regions of specialized physiological function. The
      molecular components driving the process of nephron development are not well
      understood. To identify genes that may be informative in this process we
      conducted a transcriptional profiling screen using Wnt4 mutant kidneys. In Wnt4-/
      homozygous mice, condensates and pretubular aggregates are induced, however,
      epithelial renal vesicles fail to form and subsequent tubulogenesis is blocked. A
      transcriptional profile comparison between wildtype and Wnt4-/- mutant kidneys at
      E14.5 was performed using Affymetrix oligonucleotide microarrays to identify
      nephron-expressed genes. This approach identified 236 genes with expression
      levels >1.8-fold higher in wildtype versus mutant kidneys, amongst these were a
      number of known nephron component markers confirming the validity of the screen.
      These results were further detailed by wholemount in situ hybridization (WISH) of
      E15.5 urogenital systems (UGS). We annotated the spatial expression pattern of
      these genes into eight categories of expression. Genes expressed in renal vesicle
      and their derivatives, structures absent in the mutant, accounted for the largest
      number of the observed expression patterns. A number of additional genes in areas
      not directly overlapping the Wnt4 expression domain were also identified
      including the cap mesenchyme, the collecting duct, and the cortical interstitium.
      This study provides a useful compendium of molecular markers for the study of
      nephrogenesis.

PMID- 18346945
TI  - An optimized method for determination of benzene in exhaled air by gas
      chromatography-mass spectrometry using solid phase microextraction as a sampling
      technique.
AB  - The determination of benzene in exhaled air has contributed for the increase in
      the use of breath analysis in biological monitoring. This paper describes SPME as
      a sampling technique for determining benzene in exhaled air by GC-MS. A system
      was developed to generate a gaseous benzene standard by a permeation method to
      accomplish the breath analyses. The method presented good resolution,
      repeatability (the mean of %RSD values for intra-day measurements was 6.3),
      sensitivity (2.4 and 3.1 ppb for LOD and LOQ, respectively), and linearity of
      response (R(2)=0.994). After optimizing the conditions, analyses of real samples
      were performed on two groups (exposed and not exposed to benzene). The results
      presented an average of 8.2 ppb for the control group and 25.3 ppb for the
      exposed group.

PMID- 18346946
TI  - Simultaneous determination of calycosin-7-O-beta-D-glucoside, ononin,
      astragaloside IV, astragaloside I and ferulic acid in rat plasma after oral
      administration of Danggui Buxue Tang extract for their pharmacokinetic studies by
      liquid chromatography-mass spectrometry.
AB  - A sensitive and reliable high-performance liquid chromatography-mass spectrometry
      (HPLC-MS) was developed and validated for simultaneous quantification of five
      main bioactive components, i.e., calycosin-7-O-beta-D-glucoside, ononin,
      astragaloside IV, astragaloside I and ferulic acid in rat plasma after oral
      administration of Danggui Buxue Tang (DBT) extract. Plasma samples were extracted
      with solid-phase extraction (SPE) separated on an Inertsil ZORBAX C(18) column
      and detected by MS with electrospray ionization (ESI) interface in negative
      selective ion monitoring (SIM) mode. Calibration curves offered linear ranges of
      two orders of magnitude with r(2)>0.99. The method had the lower limit
      quantification of 0.55, 0.46, 1.07, 1.12 and 4.6 ng/mL for calycosin-7-O-beta-D
      glucoside, ononin, astragaloside IV, astragaloside I and ferulic acid,
      respectively, with precision less than 10%. The RSD of intra- and inter-day
      variations ranged from 2.10% to 6.19% and 2.37% to 6.72%. This developed method
      was subsequently applied to pharmacokinetic studies of the five compounds in rats
      successfully.

PMID- 18346947
TI  - Hierarchical pore structure of calcium phosphate scaffolds by a combination of
      gel-casting and multiple tape-casting methods.
AB  - The objective of this work was to design hierarchical pore structure scaffolds
      with potential applications in bone tissue regeneration. For that purpose, a
      bioceramic material such as biphasic calcium phosphate, which consists of a
      mixture of hydroxyapatite and beta-tricalcium phosphate, was selected. Multilayer
      pieces (MLP) with hierarchical pore structure were developed employing a new
      technique that combines gel casting and adding porogens, using multiple tape
      casting methods. Pieces with functionally graded porosity were fabricated using
      porogens with different sizes. The porogens used were Porlat K85 and Porlat K86
      with diameters <150 microm and 150-300 microm, respectively. Two types of
      sintered tapes, with different porosity, no cracking and enough interconnection
      size were selected. MLP with hierarchical pore structure were designed by the
      multiple tape-casting method. Interconnected pores whose sizes increase from
      interior tapes (1.6-3.6 microm) towards exterior tapes (20-51.5 microm) and
      interpenetration between tapes were achieved. Delamination or cracking were not
      observed after heat treatment. The flexural strength of pieces was investigated
      by the three-point bending test. This new combination of methods offers the
      possibility of manufacturing scaffolds with interconnected pore sizes ranging
      from 1.6 to 51.5 microm.

PMID- 18346948
TI  - A two-scale model for simultaneous sintering and crystallization of glass-ceramic
      scaffolds for tissue engineering.
AB  - Bioglass-based glass-ceramic foams have been developed recently as highly porous,
      mechanically competent, bioactive and degradable scaffolds for bone tissue
      engineering. However, the development of the material so far has been based on a
      trial-and-error approach, and the existing materials are far from being
      optimized. In this paper, a mechanism-based model is presented for sintering
      deformation of Bioglass foams. The porous foams consist of struts which, in turn,
      consist of Bioglass particles. A corresponding two-scale model is developed based
      on existing viscous sintering models. Crystallization plays a key role in the
      sintering deformation of Bioglass foams and is taken into account in the model.
      Qualitative comparison between the model predictions and experimental
      observations is presented, showing that the model is able to capture the
      complicated interplay between crystallization and viscous flow during the
      sintering process.

PMID- 18346949
TI  - Biomimetic modification of the TiO(2)/glass composite Ecopore with heparinized
      collagen and the osteoinductive factor BMP-2.
AB  - The porous TiO(2)/glass composite Ecopore has potential applications in hard
      tissue replacement. We describe the modification of Ecopore with the growth
      factor bone morphogenetic protein-2 (BMP-2) to add osteoinductive properties.
      Ecopore covalently coated with BMP-2 caused a weak induction of alkaline
      phosphatase in murine embryonal fibroblasts. In a rabbit bone defect model, BMP-2
      coated Ecopore had moderately higher bone apposition rates and ingrown bone
      quantities at 6 weeks after implantation. To overcome loss of function due to
      chemical surface coupling, we filled the pore system of Ecopore with heparinized
      collagen sponge and loaded this secondary matrix with BMP-2. Heparinization of
      collagen filling increased the BMP-2 loading capacity of the matrix approximately
      1.28-fold. Within 96 h, 17.0+/-0.1 and 10.1+/-0.2% of the used BMP-2 was released
      from non-modified and heparinized Ecopore/collagen, respectively, indicating that
      the heparin modification retarded BMP-2 release. Revealed by energy-dispersive X
      ray spectroscopy analysis of implant cross-sectional areas, BMP-2-loaded
      Ecopore/collagen had significantly higher bony ingrowth quantities in rabbits,
      with the heparinized modification yielding the highest value (16.09+/-3.51%,
      p<0.005) compared with the non-heparinized matrix (10.72+/-4.07%, p<0.05) and the
      BMP-2-free controls (5.60+/-1.47%). This suggested a beneficial effect of the
      biomimetic modification of Ecopore with heparinized collagen for bone healing and
      integration.

PMID- 18346950
TI  - Enhancement of fibroblastic proliferation on chitosan surfaces by immobilized
      epidermal growth factor.
AB  - Chitosan membranes were modified with mouse epidermal growth factor (EGF) by a
      photochemical technique. Photochemical immobilization was performed via a two
      step process, in which EGF was first reacted with a heterobifunctional cross
      linker sulfo-SANPAH (sulfosuccinimidyl 6(4'-azido-2'-nitrophenyl-amino)hexanoate)
      and then immobilized on the chitosan membrane by UV irradiation. The success of
      immobilization process was checked by Fourier transform infrared attenuated total
      reflection spectroscopy and X-ray photoelectron spectroscopy. Atomic force
      microscopy was used to evaluate the surface topography. The mitogenic effect of
      the EGF-modified chitosan membrane was investigated using mouse fibroblasts (L929
      cell line), and cell proliferation was investigated by MTT and crystal violet
      assays. The results obtained from cell culture experiments showed that
      immobilized EGF stimulated fibroblast growth on chitosan membranes, and a
      considerable difference in cell proliferation was detected on EGF-modified
      chitosan membranes.

PMID- 18346951
TI  - Osteoclast polarization is not required for degradation of bone matrix in
      rachitic FGF23 transgenic mice.
AB  - Hypophosphatemic transgenic (tg) mice overexpressing FGF23 in osteoblasts display
      disorganized growth plates and reduced bone mineral density characteristic of
      rickets/osteomalacia. These FGF23 tg mice were used as an in vivo model to
      examine the relation between osteoclast polarization, secretion of proteolytic
      enzymes and resorptive activity. Tg mice had increased mRNA expression levels of
      the osteoblast differentiation marker Runx2 and mineralization-promoting proteins
      alkaline phosphatase and bone sialoprotein in the long bones compared to wild
      type (wt) mice. In contrast, expression of alpha1(I) collagen, osteocalcin,
      dentin matrix protein 1 and osteopontin was unchanged, indicating selective
      activation of osteoblasts promoting mineralization. The number of osteoclasts was
      unchanged in tg compared to wt mice, as determined by histomorphometry, serum
      levels of TRAP 5b activity as well as mRNA expression levels of TRAP and
      cathepsin K. However, tg mice displayed elevated serum concentrations of C
      terminal telopeptide of collagen I (CTX) indicative of increased bone matrix
      degradation. The majority of osteoclasts in FGF23 tg mice lacked ultrastructural
      morphological signs of proper polarization. However, they secreted both cathepsin
      K and MMP-9 at levels comparable to osteoclasts with ruffled borders.
      Mineralization of bone matrix thus appears essential for inducing osteoclast
      polarization but not for secretion of osteoclast proteases. Finally, release of
      CTX by freshly isolated osteoclasts was increased on demineralized compared to
      mineralized bovine bone slices, indicating that the mineral component limits
      collagen degradation. We conclude that ruffled borders are implicated in
      acidification and subsequent demineralization of the bone matrix, however not
      required for matrix degradation. The data collectively provide evidence that
      osteoclasts, despite absence of ruffled borders, effectively participate in the
      degradation of hypomineralized bone matrix in rachitic FGF23 tg mice.

PMID- 18346952
TI  - Shift work and sickness absence.
AB  - BACKGROUND: Sickness absence is increasing in public work places in Denmark where
      shift work is common. AIMS: The aim of this prospective study was to predict the
      hazard ratio (HR) of short- and long-term sickness absence due to shift work in
      Danish shift workers. METHODS: A total of 1008 shift workers and 4009 day workers
      were followed up for short- and long-time sickness absence. RESULTS: Among shift
      workers, the HR of sickness absence lasting >or=2 weeks was 0.92 (95% CI: 0.71
      1.18) for men and 0.90 for women (95% CI: 0.71-1.14). For sickness absence
      lasting >or=8 weeks, the HR was 1.33 (95% CI: 0.91-1.94) for men and 1.13 (95%
      CI: 0.81-1.59) for women. CONCLUSION: This study was inconclusive in proving any
      link between shift work and absenteeism after controlling for age, education,
      body mass index, smoking status, alcohol consumption, leisure time physical
      activity, psychosocial and physical work environment factors.

PMID- 18346953
TI  - Feasibility of a screening programme for lung cancer in former asbestos workers.
AB  - BACKGROUND: Low-dose computed tomography (CT) has been found to detect more Stage
      IA lung cancer than chest x-ray. AIMS: To investigate whether lung cancer
      screening with CT was effective and acceptable in former asbestos workers.
      METHODS: CT scanning was carried out following the protocol previously described
      in the literature. A questionnaire was used to assess cumulative asbestos
      exposure. An economic analysis was also performed. Informed consent was obtained
      from all patients. RESULTS: A total of 1119 male asbestos workers (58% of
      invited) were examined, of whom 65% were smokers or ex-smokers. Mean age was 57.1
      years with mean cumulative exposure to asbestos of 123 fibres/ml x years. Pleural
      plaques were found in 375 workers (32%), while 338 workers (29%) were included in
      the radiological follow-up, which led to 25 biopsies (13 of lung, 9 of pleura, 3
      of both) and five screen-detected lung cancers (0.4%), one in Stage I. Incidence
      rate was 149 per 10(5), equal to that in the male general population of similar
      age. The expenses for diagnosis were 1014 and 244962 Euro per screened subject
      and screen-detected lung cancer case, respectively. CONCLUSIONS: Screening
      adherence and frequency of detection were low, while costs and radiation dose
      were high. In spite of a high cumulative asbestos exposure, lung cancer risk was
      not increased relative to the general population. The screening programme was not
      felt to be cost-effective from the perspective of the government as a third-party
      funding agency.

PMID- 18346954
TI  - Managing low back pain: knowledge and attitudes of hospital managers.
AB  - BACKGROUND: Low back pain (LBP) is a major cause of work-related disability.
      Despite an increasing emphasis on the role of employers and workplace managers in
      reducing work disability, little research has been conducted in this area. AIMS:
      To identify hospital line managers' knowledge, attitudes and beliefs regarding
      LBP and its management; the difficulties encountered in managing the worker with
      LBP and the organizational needs in relation to managing LBP at work. METHODS:
      Cross-sectional survey of line managers (n = 92) at an Irish University Hospital
      using a self-administered questionnaire. Quantitative data were entered onto the
      Statistical Package for the Social Sciences (V 11) and analysed using descriptive
      statistics. Qualitative data were coded and analysed for common themes. RESULTS:
      A 64% (n = 59) response rate was achieved. Contrary to current evidence, 54% (n =
      32) of respondent managers reported that a staff member needs to be pain free
      prior to return to work (RTW). Managers reported difficulties in dealing with
      colleagues of workers with LBP and in knowing the work capacity of the worker
      with LBP. Managers demonstrated poor awareness of the importance of the manager
      worker relationship in influencing RTW. Managers believed more information,
      easier access to health services, more ergonomic training and better staff
      resources were necessary supports in facilitating the management of workers with
      LBP. CONCLUSIONS: Hospital line managers' knowledge of the evidence regarding
      their role in LBP management needs to be improved. Managers believed better
      information, improved staff resources and easier access to health and ergonomic
      services would facilitate their management of workers with LBP.

PMID- 18346955
TI  - Can pre-placement health assessments predict subsequent sickness absence?
AB  - BACKGROUND: Sickness absence is a growing economic problem, due largely to the
      financial losses it incurs. The ability to identify employees likely to take
      greater than average sickness absence may provide managers with useful
      information at the pre-placement stage. AIM: To confirm whether specific risk
      factors identified at the pre-placement health assessment could predict
      subsequent sickness absence. METHODS: A total of 400 National Health Service pre
      placement health questionnaires were analysed to allocate employees to low-,
      medium- or high-risk categories for subsequent sickness absence, using the risk
      table developed by C. J. M. Poole (Can sickness absence be predicted at the pre
      placement health assessment? Occup Med (Lond) 1999; 49:337-339) [1]. Subsequent
      sickness absence was analysed to assess if there was an association between the
      allocated category and sickness absence taken. RESULTS: Mean sickness absence
      hours per 1000 h worked were 22.5 (95% CI 18.2-27.2) in the low-risk group, 33.6
      (27.2-40.7) in the medium-risk group and 44.7 (25.1-69.9) in the high-risk group
      (analysis of variance, P <or= 0.002), demonstrating a statistically significant
      difference in sickness absence taken in subsequent years. CONCLUSIONS: The
      results confirmed Poole's hypothesis that future sickness absence can be
      predicted at the pre-placement health assessment. Certain risk factors, namely
      female sex, age, smoking, history of at least two previous episodes of low-back
      pain and previous days sickness absence identified at pre-placement assessment,
      predict a greater than average subsequent sickness absence. However, the best
      model using identified risk factors only predicted 10-12% of the variation in
      sickness absence.

PMID- 18346956
TI  - A study of South Korean casino employees and gambling problems.
AB  - BACKGROUND: Casino employees are exposed to disproportionately high levels of
      gambling, drinking and smoking compared to other occupations. Because of their
      occupation, they have the opportunity to detect and prevent pathological gambling
      (PG). AIMS: To identify differences in the mental health status and social
      attitudes towards PG among casino workers in South Korea depending upon whether
      they report any gambling problems. METHODS: Data were collected from 388 full
      time casino employees. This data provided information about the prevalence of
      gambling problems, alcohol and tobacco use and depression. Employees were grouped
      according to their scores on the Korean version of South Oaks Gambling Screen
      (SOGS), and those employees who gambled without experiencing any gambling
      problems (Group NP: SOGS = 0) and those who reported any gambling problems (Group
      P: SOGS > 0) were compared. An exploratory factor analyses identified the domains
      of casino employee social attitudes towards gambling. RESULTS: Employees who
      reported gambling problems (Group P) reported a higher prevalence of smoking,
      alcohol problems and depression (P < 0.01) compared to employees who did not
      report gambling problems (Group NP). The primary employee social attitude towards
      gambling was identified by the factor of 'Disease concept/social awareness'.
      Group NP reported more positive attitudes in this domain than Group P (P < 0.01).
      CONCLUSIONS: Employees who reported any gambling problems reported a less
      positive attitude towards developing the public health system to be responsive to
      gambling problems. These findings indicate a need to develop health education
      programmes that focus more specifically on casino employees with gambling
      problems.

PMID- 18346957
TI  - The development and validation of the Office Work Screen.
AB  - BACKGROUND: The prevalence and costs to both employers and individuals of
      musculoskeletal disorders and associated psychosocial factors are well
      documented. There is increasing evidence that early identification is the key to
      the prevention of chronicity and sickness absence. AIMS: The study aimed to
      develop and validate a screening questionnaire, capturing relevant psychosocial
      issues and musculoskeletal symptoms, to measure work instability (WI) in office
      workers. METHODS: The staged methodology was based upon Rasch analysis and
      included item banking from existing Work Instability scales and analysis of new
      data from postal surveys. The criterion validity of the emerging scale was
      examined using vocational assessments by occupational physiotherapists. RESULTS:
      A 62-item questionnaire was returned by 153 employees from two different
      settings. The data were fitted to the Rasch model and 26 items were found to fit
      model expectations (chi-square P= 0.07), satisfy strict requirements for
      unidimensionality and discriminate across expert defined levels of WI.
      Reliability was 0.9, indicating suitability for use at the individual level.
      Absence of item bias was shown for age, gender and if the individual had been off
      sick from work in the past 3 months, suggesting the scale is robust to variations
      in workforce composition and sickness absence rates. CONCLUSIONS: The Office Work
      Screen is a short questionnaire incorporating both musculoskeletal symptoms and
      relevant psychosocial factors in one dimension. This new questionnaire may
      facilitate workforce screening, individual monitoring and proactive targeting of
      interventions (for example, vocational rehabilitation) to prevent or minimize
      sickness absence in office workers.

PMID- 18346958
TI  - The universal definition of myocardial infarction: some issues and concerns.

PMID- 18346959
TI  - Off pump coronary artery bypass: a passing fad or ready for prime time?
AB  - Off pump coronary artery bypass (OPCAB) allows multivessel coronary disease to be
      bypassed surgically without the need for cardiopulmonary bypass, myocardial
      ischaemia, and in many cases ascending aortic manipulation. Many randomized
      controlled studies of OPCAB vs. on pump CABG (coronary artery bypass grafting)
      have been completed and published. Although non-inferior, OPCAB does not, in
      these trials, offer any clear benefits. As a consequence, surgeons and industry
      are losing interest in this undeniably harder technique. As the risk profile of
      patients being referred for coronary surgery is increasing, is it time for OPCAB
      to prove itself? A large, appropriately powered randomized controlled trial of
      OPCAB vs. on pump CABG in high-risk patients will determine whether it is now or
      never for OPCAB.

PMID- 18346960
TI  - Association between baseline neutrophil count, clopidogrel therapy, and clinical
      and angiographic outcomes in patients with ST-elevation myocardial infarction
      receiving fibrinolytic therapy.
AB  - AIMS: To investigate the association between neutrophil count, outcomes, and
      benefit of clopidogrel therapy in ST-elevation myocardial infarction (STEMI).
      METHODS AND RESULTS: Baseline neutrophil count was measured in 2865 patients in
      CLARITY-TIMI 28, a randomized trial of clopidogrel vs. placebo in STEMI patients
      undergoing fibrinolysis. Angiography was performed at 2-8 days following
      enrollment. Analyses were adjusted for demographics, time from symptom onset,
      Killip class, peak CK-MB, and therapies received. A baseline neutrophil count in
      the highest quartile was independently associated with the risk of cardiovascular
      (CV) death [adj (adjusted) OR (odds ratio) 5.8, P < 0.001] and congestive heart
      failure (adj OR 3.0, P = 0.009) at 30 days. Patients with higher neutrophil
      counts were less likely to achieve complete ST-segment resolution (adj OR 0.76, P
      = 0.03) or TIMI myocardial perfusion grade 2/3 (adj OR 0.71, P = 0.017).
      Clopidogrel had a lesser effect on reducing the odds of a closed infarct-related
      artery, or death or MI before angiography, in patients with a neutrophil count
      above the median (adjusted OR 0.83, 0.61-1.13) vs. in those below the median
      (adjusted OR 0.46, 0.33-0.64) (Pinteraction = 0.008). CONCLUSION: In patients
      with STEMI, higher baseline neutrophil count is associated with worse
      angiographic findings and increased CV mortality, as well as a diminished benefit
      of clopidogrel.

PMID- 18346961
TI  - Resistance to what, does it matter? How do we study it?

PMID- 18346962
TI  - The effect of pre-operative aspirin on bleeding, transfusion, myocardial
      infarction, and mortality in coronary artery bypass surgery: a systematic review
      of randomized and observational studies.
AB  - AIMS: To obtain estimates of the efficacy and safety of pre-operative aspirin in
      patients undergoing coronary artery bypass grafting (CABG). METHODS AND RESULTS:
      Eligible studies included randomized controlled trials (RCTs) and observational
      studies of patients undergoing CABG, comparing pre-operative aspirin with no
      aspirin/placebo, and reporting at least one of our primary outcomes. In eight
      RCTs (n = 805), pre-operative aspirin increased post-operative bleeding [Mean
      difference (MD), 104.9 mL; 95% confidence interval (CI), 19.2-190.6; P = 0.016]
      and reoperation [odds ratio (OR), 2.52; 95% CI, 1.18-5.38; P = 0.017), but not
      transfusion requirements (MD, 0.62 units; 95% CI, -0.06-1.30; P = 0.072).
      Subgroup analysis suggested that bleeding was increased with aspirin doses > or
      =325 mg/day, but not with lower doses. In 14 observational studies (n = 4485),
      pre-operative aspirin increased post-operative bleeding (MD, 113.6 mL; 95% CI,
      45.2-182.0; P = 0.001) and transfusion requirements (MD, 0.34; 95% CI, 0.12-0.56
      units; P = 0.002), but not reoperation (OR, 1.12; 95% CI, 0.69-1.83; P = 0.647).
      Neither analysis detected a significant effect on myocardial infarction or death.
      CONCLUSION: Pre-operative aspirin increases post-operative bleeding, but this may
      be avoided by the use of aspirin doses <325 mg/day. Most of the RCTs are old and
      the meta-analysis was underpowered for efficacy outcomes. A large randomized
      trial is necessary to determine the safety and efficacy of pre-operative aspirin
      in the setting of contemporary cardiac surgical practice.

PMID- 18346963
TI  - Safety of percutaneous coronary intervention during uninterrupted oral
      anticoagulant treatment.
AB  - AIMS: Uninterrupted anticoagulation (UAC) is assumed to increase bleeding and
      access-site complications. A common consensus is to postpone percutaneous
      coronary interventions (PCI) to reach international normalized ratio (INR) levels
      < 1.5-1.8. METHODS AND RESULTS: To assess the safety and feasibility of UAC, we
      analysed retrospectively all consecutive patients (n = 523) on warfarin therapy
      referred for PCI in four centres with a policy to interrupt anticoagulation (IAC)
      before PCI and in three centres with a long experience on UAC during PCI. Major
      bleeding, access-site complications, and major adverse cardiac events (death,
      myocardial infarction, target vessel revascularization, and stent thrombosis)
      were recorded during hospitalization. In the IAC group, warfarin was withdrawn
      for a mean of 3 days prior to PCI (mean INR 1.7). In the UAC group, mean INR
      value was 2.2. Glycoprotein IIb/IIIa (GP) inhibitors (P < 0.001) and low
      molecular-weight heparins (P < 0.001) were more often used in the IAC group.
      Major bleeding and access-site complications were more common in the IAC group
      (5.0% vs. 1.2%, P = 0.02 and 11.3% vs. 5.0%, P = 0.01, respectively) than in the
      UAC group. After adjusting for propensity score, the group difference in access
      site complications remained significant [OR (odds ratio) 2.8, 95% CI (confidence
      interval) 1.3-6.1, P = 0.008], but did not remain significant in major bleeding
      (OR 3.9, 95% CI 1.0-15.3, P = 0.05). In multivariable analysis, femoral access
      (OR 9.9, 95% CI 1.3-75.2), use of access-site closure devices (OR 2.1, 95% CI 1.1
      4.0), low-molecular-weight heparin (OR 2.7, 95% CI 1.1-6.7) and old age predicted
      access-site complications, and the use of GP inhibitors (OR 3.0, 95% CI 1.0-9.1)
      remained as a predictor of major bleeding. CONCLUSION: Our study shows that PCI
      is a safe procedure during UAC with no excess bleeding complications.

PMID- 18346964
TI  - Re-estimation of internal dose from natural radionuclides for Chinese adult men.
AB  - Based on recent research, related literature data and updated model parameter
      values, the present internal radiation dose from intakes of radionuclides for
      Chinese adult men (except for radon and its short-lived decay products) has been
      re-estimated. Radiation doses obtained by using both direct and indirect
      approaches have been compared. It is shown that the total annual committed
      effective dose in Chinese men accounts for approximately 0.43 mSv, 43% higher
      than the world reference value. The average annual dose from (40)K is quite near
      to the world reference value, but those from the (238)U-series (with (235)U
      series) and (232)Th-series are 2.1- and 3.2-fold higher, respectively. The dose
      by ingestion is about two orders of magnitude higher than that by inhalation.
      (40)K is the greatest contributor to the total dose, while, in the decreasing
      order, (210)Po, (210)Pb, (228)Ra and (14)C are lower. Other radionuclides
      contribute very little dose ( approximately 2.6%). These results provide a useful
      basis for clarifying the characteristics of natural radiation exposure and for
      establishing related reference values for Chinese adult men.

PMID- 18346965
TI  - Limitations of the use of the vertical cut-off to calculate cosmic-ray
      propagation in the Earth's atmosphere.

PMID- 18346966
TI  - Analysis of the frequency of interventional cardiology in various European
      countries.
AB  - The contribution of interventional cardiology procedures to the population dose
      in Europe is poorly known. The estimation of the population dose from these
      procedures requires knowledge of both the typical dose received by patients and
      an estimate of the number of procedures undertaken annually. Data on the number
      of cardiology procedures in various European countries are available on the
      internet for a number of countries. However, this data set is incomplete or out
      of date. This paper describes the statistical analysis undertaken to estimate the
      number of interventional cardiology procedures in a number of European countries
      for 2007. Estimates of the number of procedures are given. On average, the number
      of cardiac catheterisations per million population is 5346, percutaneous
      transluminal coronary angioplasty is 1599 and 1214 stent procedures. In addition,
      there are an estimated 973 pacemaker insertions per million population.

PMID- 18346967
TI  - Small ncRNA transcriptome analysis from Aspergillus fumigatus suggests a novel
      mechanism for regulation of protein synthesis.
AB  - Small non-protein-coding RNAs (ncRNAs) have systematically been studied in
      various model organisms from Escherichia coli to Homo sapiens. Here, we analyse
      the small ncRNA transcriptome from the pathogenic filamentous fungus Aspergillus
      fumigatus. To that aim, we experimentally screened for ncRNAs, expressed under
      various growth conditions or during specific developmental stages, by generating
      a specialized cDNA library from size-selected small RNA species. Our screen
      revealed 30 novel ncRNA candidates from known ncRNA classes such as small nuclear
      RNAs (snRNAs) and C/D box-type small nucleolar RNAs (C/D box snoRNAs).
      Additionally, several candidates for H/ACA box snoRNAs could be predicted by a
      bioinformatical screen. We also identified 15 candidates for ncRNAs, which could
      not be assigned to any known ncRNA class. Some of these ncRNA species are
      developmentally regulated implying a possible novel function in A. fumigatus
      development. Surprisingly, in addition to full-length tRNAs, we also identified
      5'- or 3'-halves of tRNAs, only, which are likely generated by tRNA cleavage
      within the anti-codon loop. We show that conidiation induces tRNA cleavage
      resulting in tRNA depletion within conidia. Since conidia represent the resting
      state of A. fumigatus we propose that conidial tRNA depletion might be a novel
      mechanism to down-regulate protein synthesis in a filamentous fungus.

PMID- 18346968
TI  - Autoregulation of the Escherichia coli melR promoter: repression involves four
      molecules of MelR.
AB  - The Escherichia coli MelR protein is a transcription activator that autoregulates
      its own promoter by repressing transcription initiation. Optimal repression
      requires MelR binding to a site that overlaps the melR transcription start point
      and to upstream sites. In this work, we have investigated the different
      determinants needed for optimal repression and their spatial requirements. We
      show that repression requires a complex involving four DNA-bound MelR molecules,
      and that the global CRP regulator plays little or no role.

PMID- 18346969
TI  - Positional gene enrichment analysis of gene sets for high-resolution
      identification of overrepresented chromosomal regions.
AB  - The search for feature enrichment is a widely used method to characterize a set
      of genes. While several tools have been designed for nominal features such as
      Gene Ontology annotations or KEGG Pathways, very little has been proposed to
      tackle numerical features such as the chromosomal positions of genes. For
      instance, microarray studies typically generate gene lists that are
      differentially expressed in the sample subgroups under investigation, and when
      studying diseases caused by genome alterations, it is of great interest to
      delineate the chromosomal regions that are significantly enriched in these lists.
      In this article, we present a positional gene enrichment analysis method (PGE)
      for the identification of chromosomal regions that are significantly enriched in
      a given set of genes. The strength of our method relies on an original query
      optimization approach that allows to virtually consider all the possible
      chromosomal regions for enrichment, and on the multiple testing correction which
      discriminates truly enriched regions versus those that can occur by chance. We
      have developed a Web tool implementing this method applied to the human genome
      (http://www.esat.kuleuven.be/~bioiuser/pge). We validated PGE on published lists
      of differentially expressed genes. These analyses showed significant
      overrepresentation of known aberrant chromosomal regions.

PMID- 18346970
TI  - The bacterial and mitochondrial ribosomal A-site molecular switches possess
      different conformational substates.
AB  - The A site of the small ribosomal subunit participates in the fidelity of
      decoding by switching between two states, a resting 'off' state and an active
      decoding 'on' state. Eight crystal structures of RNA duplexes containing two
      minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G
      mutant or bacteria have been solved. The resting 'off' state of the mitochondrial
      wild-type A site is surprisingly different from that of the bacterial A site. The
      mitochondrial A1555G mutant has two types of the 'off' states; one is similar to
      the mitochondrial wild-type 'off' state and the other is similar to the bacterial
      'off' state. Our present results indicate that the dynamics of the A site in
      bacteria and mitochondria are different, a property probably related to the small
      number of tRNAs used for decoding in mitochondria. Based on these structures, we
      propose a hypothesis for the molecular mechanism of non-syndromic hearing loss
      due to the mitochondrial A1555G mutation.

PMID- 18346971
TI  - Inhibition of HIV-1 by multiple siRNAs expressed from a single microRNA
      polycistron.
AB  - RNA interference (RNAi) is a powerful approach to inhibit human immunodeficiency
      virus type 1 (HIV-1) replication. However, HIV-1 can escape from RNAi-mediated
      antiviral therapy by selection of mutations in the targeted sequence. To prevent
      viral escape, multiple small interfering RNAs (siRNAs) against conserved viral
      sequences should be combined. Ideally, these RNA inhibitors should be expressed
      simultaneously from a single transgene transcript. In this study, we tested a
      multiplex microRNA (miRNA) expression strategy by inserting multiple effective
      anti-HIV siRNA sequences in the miRNA polycistron mir-17-92. Individual anti-HIV
      miRNAs that resemble the natural miRNA structures were optimized by varying the
      siRNA position in the hairpin stem to obtain maximal effectiveness against
      luciferase reporters and HIV-1. We show that an antiviral miRNA construct can
      have a greater intrinsic inhibitory activity than a conventional short hairpin
      (shRNA) construct. When combined in a polycistron setting, the silencing activity
      of an individual miRNA is strongly boosted. We demonstrate that HIV-1 replication
      can be efficiently inhibited by simultaneous expression of four antiviral siRNAs
      from the polycistronic miRNA transcript. These combined results indicate that a
      multiplex miRNA strategy may be a promising therapeutic approach to attack escape
      prone viral pathogens.

PMID- 18346972
TI  - A dual-tag microarray platform for high-performance nucleic acid and protein
      analyses.
AB  - DNA microarrays serve to monitor a wide range of molecular events, but emerging
      applications like measurements of weakly expressed genes or of proteins and their
      interaction patterns will require enhanced performance to improve specificity of
      detection and dynamic range. To further extend the utility of DNA microarray
      based approaches we present a high-performance tag microarray procedure that
      enables probe-based analysis of as little as 100 target cDNA molecules, and with
      a linear dynamic range close to 10(5). Furthermore, the protocol radically
      decreases the risk of cross-hybridization on microarrays compared to current
      approaches, and it also allows for quantification by single-molecule analysis and
      real-time on-chip monitoring of rolling-circle amplification. We provide proof of
      concept for microarray-based measurement of both mRNA molecules and of proteins,
      converted to tag DNA sequences by padlock and proximity probe ligation,
      respectively.

PMID- 18346973
TI  - Diabetes problem solving by youths with type 1 diabetes and their caregivers:
      measurement, validation, and longitudinal associations with glycemic control.
AB  - OBJECTIVES: This article introduces a new measure of problem-solving skills of
      youths with type 1 diabetes (T1DM) and adult caregivers in correcting glycemic
      fluctuations. METHODS: The Diabetes Problem Solving Interview (DPSI), a
      structured interview, was validated during a pilot study of a behavioral
      intervention. DPSI data and measures of diabetes management were obtained at
      baseline from 114 youths (ages 9-14.5) and 109 caregivers. Glycosylated
      hemoglobin (HbA(1c)) was measured quarterly over 9 months. RESULTS: Results
      confirmed the psychometric adequacy of the DPSI. For caregivers, but not youths,
      low DPSI scores (indicating poor problem-solving skills) were significantly
      associated with worse HbA(1c) over 9 months. CONCLUSIONS: The DPSI has clinical
      and research utility as a measure of diabetes problem-solving skills.
      Identification and targeted remediation of caregivers' deficient diabetes problem
      solving skills or promotion of youths' utilization of these skills could possibly
      enhance glycemic control in youths with T1DM.

PMID- 18346974
TI  - Do TNF-blockers reduce or induce uveitis?

PMID- 18346975
TI  - Undergraduate rheumatology: can peer-assisted learning by medical students
      deliver equivalent training to that provided by specialist staff?
AB  - OBJECTIVE: This study addressed whether medical students using peer-assisted
      learning (PAL) can deliver training comparable with didactic teaching provided by
      a specialist. METHODS: Twelve senior students were trained in PAL and the gait,
      arms, legs, spine (GALS) screening technique for musculoskeletal system (MSS)
      examination. The students recruited and trained 45 year-2 students in the use of
      GALS. Nineteen students were recruited by a physiotherapist for GALS training
      tutorials. Trainee responses were compared by analysis of pre/post training
      confidence (using 100 mm visual analogue scale), course experience questionnaires
      (using a 5-point Likert scale) including free text comments, and in end of year
      examinations. RESULTS: Trainee confidence increased after PAL training from 3.7
      to 89.9 (P < 0.0001). There were no significant differences in confidence levels
      from student trainees after PAL when compared with expert-led teaching. Results
      from course experience questionnaires demonstrated benefits in all parameters
      investigated with all students recommending PAL training. No differences between
      PAL and expert-led training were observed. Free-text comments showed that PAL
      trained students perceived that this learning technique has potential to be
      applied to other areas of training, an observation not raised by expert-trained
      students. Examination results revealed that PAL-trained and expert-tutored
      students were respectively, 1.4 and 1.3 times more likely to pass the MSS
      examination, when compared with students undertaking standard training (P < 0.002
      and P = 0.0001, respectively). CONCLUSION: PAL is a useful adjunct to
      musculoskeletal clinical skills training. Students using PAL techniques offered a
      comparable level of training with that provided by an expert.

PMID- 18346976
TI  - Intravenous immunoglobulin therapy in pregnant patients affected with systemic
      lupus erythematosus and recurrent spontaneous abortion.
AB  - OBJECTIVES: We aimed to test the maternal and fetal outcome of SLE patients who
      suffered from recurrent spontaneous abortion (RSA) treated with intravenous
      immunoglobulin (IVIg) alone during pregnancy and whether the clinical response to
      IVIg treatment is accompanied by modifications of SLE-associated antibodies and
      of complement levels. METHODS: Twelve SLE-RSA pregnant patients were treated with
      high-dose IVIg and compared with 12 SLE-RSA pregnant patients treated with
      prednisolone and NSAIDs. They were evaluated for the clinical response [lupus
      activity index-pregnancy (LAI-P) scale] and for ANA, anti-dsDNA, anti Ro/SS-A or
      La/SS-B, aCL, LAC, C4, C3 before and during pregnancy, and before and after each
      treatment course. Pregnancy outcome in the two groups was also evaluated.
      RESULTS: The groups characteristics were homogeneous at the beginning of
      pregnancy. A beneficial clinical response following IVIg treatment was noted in
      all patients and mean LAI-P decreased from 0.72 +/- 0.43 at the beginning of
      pregnancy to 0.13 +/- 0.19 at the end of pregnancy (P < 0.0001). Antibodies and
      complement levels tended to normalize in most of the patients. These clinical and
      laboratory improvements were significant with respect to the control group.
      Pregnancy was successfully carried out in 12/12 (100%) SLE-RSA patients with a
      mean Apgar score of 8.92. Three patients in the control group got aborted (25%).
      CONCLUSIONS: IVIg has a high response rate among SLE-RSA pregnant patients and
      may be considered safe and effective.

PMID- 18346977
TI  - T lymphocytes in patients with primary vasculitis: expansion of CD8+ T cells with
      the propensity to activate polymorphonuclear neutrophils.
AB  - OBJECTIVES: To gain insight into the immune pathogenesis of primary ANCA
      associated vasculitides, the prevalence of circulating T lymphocytes expressing
      CD11b as a marker for activation was analysed in patients with WG or microscopic
      polyangiitis. METHODS; Receptor expression and IFNgamma synthesis were measured
      in T cells of patients with active disease by cytofluorometry and compared with
      expression in patients in remission and in healthy donors. RESULTS: During active
      disease, a small but conspicuous population of CD8+CD28+CD11b+ was found which
      produced IFNgamma. In healthy donors and in patients in remission or undergoing
      immunosuppressive therapy, CD11b was exclusively associated with CD8+CD28- cells,
      the latter being more frequent in patients with long-lasting or severe disease.
      In vitro experiments confirmed that CD11b is up-regulated when T cells are
      activated. After multiple rounds of restimulation, the CD11b expression persists
      whereas CD28 expression is lost, compatible with the notion that CD8+CD28+CD11b+
      represents a transient phenotype in the course of T-cell activation. The IFNgamma
      producing T cells activated polymorphonuclear neutrophils (PMN) to express MHC
      class II, thus generating the same PMN phenotype as in patients with active ANCA
      associated vasculitis. A similar PMN phenotype could be generated by cultivation
      with supernatants of activated T cells or by IFNgamma alone, but not by
      antibodies to proteinase 3. CONCLUSIONS: In active primary vasculitis, a small
      population of CD8+ T cells, identified by the expression of CD11b, expands,
      producing IFNgamma. These T cells could activate PMN, thus generating a long
      living and potentially destructive PMN phenotype.

PMID- 18346978
TI  - Methicillin-resistant Staphylococcus aureus preventing strategy in cardiac
      surgery.
AB  - OBJECTIVES: The aim of this survey was to elucidate the efficacy of methicillin
      resistant Staphylococcus aureus (MRSA) preventing strategy in our institution by
      investigating the incidence and evaluating the morbidity and mortality associated
      with this multi-resistant virulent organism. METHODS: A prospective observational
      cohort among patients submitted to cardiovascular surgical procedures was
      conducted from 1 January 1997 to 31 December 2005. Preventing strategy included
      active screening programs by nasal swabs for all patients admitted from other
      hospitals or being at risk for developing infectious complications. Carriers or
      infected patients remained isolated and were treated promptly. Furthermore, all
      newly employed health care workers were screened for MRSA and carriers were
      treated with mupirocin until the eradication of the pathogen. RESULTS: Throughout
      the 9-year study period 826 infectious complications were registered among 15,270
      cardiac surgical patients. Total infection rate was 5.4%. MRSA was identified in
      86 patients; 56 patients proved carriers and 30 infected. The MRSA associated
      infection rate was 0.2%. During this period of time mean ICU stay was 1.7 days
      and ICU mortality rate was 2.9%. MRSA infected patients presented a mean ICU stay
      of 46.5 days and a mortality rate of 30%. In ten patients, MRSA was detected in
      tracheal secretions, in four patients in swabs taken from donor site infection
      and in four patients from superficial sternal surgical wound. In ten patients the
      pathogen was isolated from cultures of the surgical site drainage and the
      diagnosis of post-sternotomy mediastinitis was confirmed. The remaining two
      patients were defined as having severe sepsis; MRSA was documented in central
      venous catheter tips and blood cultures. CONCLUSIONS: The prompt determination,
      isolation and appropriate treatment of MRSA patients admitted from other
      institutions combined with the detection and elimination of carriers among new
      health care workers and patients at high risk of developing infectious
      complications prevented further spread of the pathogen.

PMID- 18346979
TI  - Atrogin-1 ubiquitin ligase is upregulated by doxorubicin via p38-MAP kinase in
      cardiac myocytes.
AB  - AIMS: Doxorubicin (DOX) is one of the most effective anti-neoplastic agents;
      however, its clinical use is limited by drug-induced cardiomyopathy. The
      molecular mechanisms responsible for this toxicity remain to be fully addressed.
      In the present study, we investigated the involvement of atrogin-1, one of the
      muscle-specific ubiquitin ligases, in DOX-induced cardiotoxicity. METHODS AND
      RESULTS: This method involved intraperitoneal administration of DOX-induced
      atrogin-1 in the hearts and skeletal muscles of C57BL/6 mice. Consistently,
      atrogin-1 mRNA was upregulated with DOX treatment in cultured rat neonatal
      cardiomyocytes. Adenoviral transfer of atrogin-1 induced a reduction in cell size
      that was ameliorated by the ubiquitin proteasome inhibitor, MG-132. The
      transduction of constitutively active Akt (caAkt), a serine/threonine protein
      kinase, inhibited the DOX-mediated induction of atrogin-1. The phosphorylation
      status of Akt and its downstream target, FOXO, was not affected by DOX. DOX
      treatment did not activate the atrogin-1 promoter that contains FOXO-binding
      sites, suggesting that DOX induced atrogin-1 without modulating the Akt/FOXO
      pathway; importantly, DOX activated p38-mitogen-activated protein kinase (MAPK)
      and c-Jun N-terminal kinase (JNK). Furthermore, pharmacological inhibition of p38
      MAPK, but not JNK, abrogated DOX-mediated induction of atrogin-1. Finally,
      adenoviral transfer of caAkt inhibited the DOX-induced p38-MAPK activation.
      CONCLUSIONS: DOX induces atrogin-1 through a p38-MAPK-dependent pathway in
      cardiac myocytes. Constitutive activation of Akt negatively regulates DOX
      mediated atrogin-1 induction by inhibiting p38-MAPK activity as a novel
      mechanism.

PMID- 18346980
TI  - Celestial3D: a novel method for 3D visualization of familial data.
AB  - SUMMARY: Traditional two-dimensional (2D) software programs for drawing pedigrees
      are limited when dealing with extended pedigrees. In successive generations, the
      number of individuals grows exponentially, leading to an unworkable amount of
      space required in the horizontal direction for 2D displays. In addition, it is
      not always possible to place closely related individuals near each other due to
      the lack of space in 2Ds. To address these issues we have developed three
      dimensional (3D) pedigree drawing techniques to enable clearer visualization of
      extended pedigrees. Currently no other methods are available for displaying
      extended pedigrees in 3Ds. We have made freely available a software tool-
      'Celestial3D'--that implements these novel techniques. AVAILABILITY: Freely
      available to non-commercial users.

PMID- 18346981
TI  - 'Do you feel that your life is empty?' The clinical utility of a one-off question
      for detecting depression in elderly care home residents.

PMID- 18346982
TI  - A pagetic elderly lady with back pain.
AB  - An elderly lady suffering from Paget's disease presented with severe back pain
      after sustaining a fall. The rise in inflammatory markers and poor response to
      analgesics led to the diagnosis of septic discitis [corrected] that was confirmed
      by MRI. A high index of suspicion for septic discitis [corrected] is necessary in
      elderly patients presenting with back pain and an associated rise in inflammatory
      markers.

PMID- 18346983
TI  - Common variation in the FTO gene alters diabetes-related metabolic traits to the
      extent expected given its effect on BMI.
AB  - OBJECTIVE: Common variation in the FTO gene is associated with BMI and type 2
      diabetes. Increased BMI is associated with diabetes risk factors, including
      raised insulin, glucose, and triglycerides. We aimed to test whether FTO genotype
      is associated with variation in these metabolic traits. RESEARCH DESIGN AND
      METHODS: We tested the association between FTO genotype and 10 metabolic traits
      using data from 17,037 white European individuals. We compared the observed
      effect of FTO genotype on each trait to that expected given the FTO-BMI and BMI
      trait associations. RESULTS: Each copy of the FTO rs9939609 A allele was
      associated with higher fasting insulin (0.039 SD [95% CI 0.013-0.064]; P =
      0.003), glucose (0.024 [0.001-0.048]; P = 0.044), and triglycerides (0.028 [0.003
      0.052]; P = 0.025) and lower HDL cholesterol (0.032 [0.008-0.057]; P = 0.009).
      There was no evidence of these associations when adjusting for BMI. Associations
      with fasting alanine aminotransferase, gamma-glutamyl-transferase, LDL
      cholesterol, A1C, and systolic and diastolic blood pressure were in the expected
      direction but did not reach P < 0.05. For all metabolic traits, effect sizes were
      consistent with those expected for the per allele change in BMI. FTO genotype was
      associated with a higher odds of metabolic syndrome (odds ratio 1.17 [95% CI 1.10
      1.25]; P = 3 x 10(-6)). CONCLUSIONS: FTO genotype is associated with metabolic
      traits to an extent entirely consistent with its effect on BMI. Sample sizes of
      >12,000 individuals were needed to detect associations at P < 0.05. Our findings
      highlight the importance of using appropriately powered studies to assess the
      effects of a known diabetes or obesity variant on secondary traits correlated
      with these conditions.

PMID- 18346984
TI  - Decreased lipoprotein clearance is responsible for increased cholesterol in LDL
      receptor knockout mice with streptozotocin-induced diabetes.
AB  - OBJECTIVE: Patients with diabetes often have dyslipidemia and increased
      postprandial lipidmia. Induction of diabetes in LDL receptor (Ldlr(-/-)) knockout
      mice also leads to marked dyslipidemia. The reasons for this are unclear.
      RESEARCH DESIGN AND METHODS: We placed Ldlr(-/-) and heterozygous LDL receptor
      knockout (Ldlr(+/-)) mice on a high-cholesterol (0.15%) diet, induced diabetes
      with streptozotocin (STZ), and assessed reasons for differences in plasma
      cholesterol. RESULTS: STZ-induced diabetic Ldlr(-/-) mice had plasma cholesterol
      levels more than double those of nondiabetic controls. Fast-performance liquid
      chromatography and ultracentrifugation showed an increase in both VLDL and LDL.
      Plasma VLDL became more cholesterol enriched, and both VLDL and LDL had a greater
      content of apolipoprotein (apo)E. In LDL the ratio of apoB48 to apoB100 was
      increased. ApoB production, assessed using [(35)S]methionine labeling in Triton
      WR1339-treated mice, was not increased in fasting STZ-induced diabetic mice.
      Similarly, postprandial lipoprotein production was not increased. Reduction of
      cholesterol in the diet to normalize the amount of cholesterol intake by the
      control and STZ-induced diabetic animals reduced plasma cholesterol levels in STZ
      induced diabetic mice, but plasma cholesterol was still markedly elevated
      compared with nondiabetic controls. LDL from STZ-induced diabetic mice was
      cleared from the plasma and trapped more rapidly by livers of control mice. STZ
      treatment reduced liver expression of the proteoglycan sulfation enzyme, heparan
      sulfate N-deacetylase/N-sulfotrasferase-1, an effect that was reproduced in
      cultured hepatocytyes by a high glucose-containing medium. CONCLUSIONS: STZ
      induced diabetic, cholesterol-fed mice developed hyperlipidemia due to a non-LDL
      receptor defect in clearance of circulating apoB-containing lipoproteins.

PMID- 18346985
TI  - A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel
      activity and beta-cell glucose sensing is associated with type 2 diabetes in
      adults.
AB  - OBJECTIVE: ATP-sensitive K(+) channels (K(ATP) channels) link glucose metabolism
      to the electrical activity of the pancreatic beta-cell to regulate insulin
      secretion. Mutations in either the Kir6.2 or sulfonylurea receptor (SUR) 1
      subunit of the channel have previously been shown to cause neonatal diabetes. We
      describe here an activating mutation in the ABCC8 gene, encoding SUR1, that is
      associated with the development of type 2 diabetes only in adults. RESEARCH
      DESIGN AND METHODS: Recombinant K(ATP) channel subunits were expressed using
      pIRES2-based vectors in human embryonic kidney (HEK) 293 or INS1(832/13) cells
      and the subcellular distribution of c-myc-tagged SUR1 channels analyzed by
      confocal microscopy. K(ATP) channel activity was measured in inside-out patches
      and plasma membrane potential in perforated whole-cell patches. Cytoplasmic
      [Ca(2+)] was imaged using Fura-Red. RESULTS: A mutation in ABCC8/SUR1, leading to
      a Y356C substitution in the seventh membrane-spanning alpha-helix, was observed
      in a patient diagnosed with hyperglycemia at age 39 years and in two adult
      offspring with impaired insulin secretion. Single K(ATP) channels incorporating
      SUR1-Y356C displayed lower sensitivity to MgATP (IC(50) = 24 and 95 micromol/l
      for wild-type and mutant channels, respectively). Similar effects were observed
      in the absence of Mg(2+), suggesting an allosteric effect via associated Kir6.2
      subunits. Overexpression of SUR1-Y356C in INS1(832/13) cells impaired glucose
      induced cell depolarization and increased in intracellular free Ca(2+)
      concentration, albeit more weakly than neonatal diabetes-associated SUR1 mutants.
      CONCLUSIONS: An ABCC8/SUR1 mutation with relatively minor effects on K(ATP)
      channel activity and beta-cell glucose sensing causes diabetes in adulthood.
      These data suggest a close correlation between altered SUR1 properties and
      clinical phenotype.

PMID- 18346986
TI  - 5-Lipoxygenase, but not 12/15-lipoxygenase, contributes to degeneration of
      retinal capillaries in a mouse model of diabetic retinopathy.
AB  - OBJECTIVE: Lipoxygenases are regulators of chronic inflammation and oxidative
      stress generation. We evaluated the role of 5- and 12-lipoxygenases in the
      development of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Wild-type mice,
      5-lipoxygenase-deficient mice, and 12/15-lipoxygenase-deficient mice were
      assessed 1) after 9 months of diabetes for retinal histopathology and leukotriene
      receptor expression and 2) after 3 months of diabetes for leukostasis and retinal
      superoxide generation. RESULTS: Diabetic wild-type mice developed the expected
      degeneration of retinal capillaries and pericytes and increases in both
      leukostasis and superoxide production (P < 0.006). We found no evidence of
      diabetes-induced degeneration of retinal ganglion cells in these animals. The
      vascular histopathology was significantly inhibited in 5-lipoxygenase-deficient
      mice, but not in 12/15-lipoxygenase-deficient mice. Retinas from diabetic 5
      lipoxygenase-deficient mice also had significantly less leukostasis, superoxide
      production, and nuclear factor-kappaB (NF-kappaB) expression (all P < 0.006),
      whereas retinas from diabetic 12/15-lipoxygenase-deficient mice had significantly
      less leukostasis (P < 0.005) but not superoxide production or NF- kappaB
      expression. Retinas from diabetic wild-type mice were enriched with receptors for
      the 5-lipoxygenase metabolite leukotriene B(4). Diabetes-induced histological and
      biochemical alterations were significantly reduced in 5-lipoxygenase-deficient
      mice, but not 12/15-lipoxygenase-deficient mice. CONCLUSIONS: 5-Lipoxygenase
      represents a novel pathway for therapeutic intervention of diabetic retinopathy.

PMID- 18346987
TI  - Use of nasal continuous positive airway pressure during retrieval of neonates
      with acute respiratory distress.
AB  - OBJECTIVE: Although nasal continuous positive airway pressure is widely used in
      neonatal units, its use in neonatal transport is not yet established. Previous
      reports have been limited to small numbers of primary road transports and larger
      numbers of return transports while its use in air transportation has not been
      reported. The aim of this study was to assess the safety and effectiveness of
      transporting neonates and infants by road or air while treated with nasal
      continuous positive airway pressure. METHODS: We conducted a retrospective review
      of the records of all infants transported between January 1, 2004, and November
      1, 2005. RESULTS: A total of 220 infants were treated with nasal continuous
      positive airway pressure; of these, 13 infants (6%) were intubated before
      transport, leaving 207 infants transported on a median nasal continuous positive
      airway pressure of 7 cm H(2)O. Thirty infants were transported by fixed or rotary
      wing aircraft and 190 by road. No infants required intubation or bag and mask
      ventilation during transport. Twenty-eight infants (13%) required intubation
      within 24 hours of arrival at the receiving hospital, 4 infants (2%) were
      intubated > 24 hours after arrival, 11 infants (5%) were intubated for surgery,
      and 164 infants (73%) were never intubated. A total of 111 infants (50%) were
      preterm and < 72 hours old at transport, and 32 infants (15%) were < or = 32
      weeks' gestational age and < 72 hours old at transport. Fraction of inspired
      oxygen was significantly lower at the end of transport (0.45 vs 0.34).
      CONCLUSIONS: Nasal continuous positive airway pressure is effective and has an
      acceptable safety margin for the road-based transportation of infants with acute
      respiratory distress. Air transport is feasible but larger studies are required
      to assess safety.

PMID- 18346988
TI  - Pediatric residents' clinical and educational experiences with end-of-life care.
AB  - OBJECTIVE: The objective of this study was to document the frequency of pediatric
      resident experiences with end-of-life care for children and the educational
      context for these experiences, as well as to determine whether residents deem
      their preparatory training adequate. METHODS: An Internet-based survey was
      distributed to all categorical pediatric residents at the Johns Hopkins
      Children's Center. Survey items asked residents to (1) quantify their experiences
      with specific responsibilities associated with the death of a pediatric patient,
      (2) identify their educational experiences, and (3) respond to Likert scale
      statements of, "I feel adequately trained to... ." The responsibilities were
      discussion of withdrawal/limitation of life-sustaining therapy, symptom
      management, declaration of death, discussion of autopsy, completion of a death
      certificate, seeking self-support, and follow-up with families. RESULTS: Forty
      (50%) of 80 residents completed the survey. Residents had been present for a mean
      (+/- SD) of 4.7 (+/- 3.0) patient deaths. More than 50% of residents had
      participated in discussions of withdrawal/limitation of life-sustaining therapy,
      symptom management, completing a death certificate, and seeking personal support;
      however, <50% of residents had been taught how to hold discussions of
      withdrawal/limitation of life-sustaining therapy, declare death, discuss autopsy,
      complete a death certificate, and have follow-up with families. Residents did not
      feel adequately trained in any of these areas. CONCLUSION: Pediatric residents
      have limited experience with pediatric end-of-life care and highly varied
      educational experiences and do not feel adequately trained to fulfill the
      responsibilities associated with providing end-of-life care for children.
      Overall, this perception does not improve with increased level of training. This
      study identifies several target areas for curricular intervention that may
      ultimately improve the end-of-life experience for our pediatric patients and
      their families and the young physicians who care for them.

PMID- 18346989
TI  - Serum cytokine and chemokine profiles in neonates with meconium aspiration
      syndrome.
AB  - OBJECTIVES: Various inflammatory cytokines and chemokines are thought to be
      associated with the pathophysiology of meconium aspiration syndrome. To clarify
      any such association, we compared various serum cytokine and chemokine profiles
      in patients with and without meconium aspiration syndrome. PATIENTS AND METHODS:
      Using a highly sensitive fluorescence microsphere method, 17 types of cytokines
      and chemokines in sera were measured in 11 neonatal patients with meconium
      aspiration syndrome, 16 neonatal patients without meconium aspiration syndrome,
      and 9 healthy children. RESULTS: The concentrations of 8 types of proinflammatory
      cytokines and chemokines were significantly higher in the meconium aspiration
      syndrome group than in healthy controls: interleukin-1beta, interleukin-6,
      interleukin-8, granulocyte-macrophage colony-stimulating factor, granulocyte
      colony-stimulating factor, interferon-gamma, macrophage inflammatory protein
      1beta, and tumor necrosis factor-alpha. Six types of proinflammatory cytokines
      and chemokines were significantly higher in the meconium aspiration syndrome
      group than in the nonmeconium aspiration syndrome group: interleukin-6,
      interleukin-8, granulocyte-macrophage colony-stimulating factor, granulocyte
      colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha.
      Serum concentrations of interleukin-10 (anti-inflammatory cytokine) in the
      meconium aspiration syndrome group were higher than those in both the nonmeconium
      aspiration syndrome group and healthy children group (P = .007 and 0.001,
      respectively). CONCLUSIONS: Most types of proinflammatory cytokines and
      chemokines in sera of neonates with meconium aspiration syndrome were higher than
      those without meconium aspiration syndrome, giving support to the suggestion that
      elevated levels are associated with the pathogenesis of meconium aspiration
      syndrome.

PMID- 18346991
TI  - Sex hormone-binding globulin and testosterone in individuals with childhood
      diabetes.
AB  - OBJECTIVE: Insulin downregulates hepatic production of sex hormone-binding
      globulin (SHBG), which in turn influences sex hormone bioavailability. The
      effects of childhood-onset diabetes and insulin resistance in nondiabetic
      individuals on SHBG and testosterone in children and young adults are poorly
      understood. RESEARCH DESIGN AND METHODS: Individuals with diabetes diagnosed at
      <18 years of age (n = 48) and their siblings without diabetes (n = 47) were
      recruited for the Chicago Childhood Diabetes Registry Family Study. SHBG and
      total and free testosterone were measured. Participants ranged in age from 10 to
      32 years; 39% were non-Hispanic white. The majority of individuals with diabetes
      had the classic type 1 phenotype (75%), while the remainder exhibited features of
      type 2 or mixed diabetes; 96% were treated with insulin. RESULTS: SHBG and total
      testosterone were higher in male subjects with diabetes compared with those in
      male siblings. Elevated SHBG was associated with the absence of endogenous
      insulin independent of sex; elevated total testosterone was similarly associated
      with the absence of C-peptide for male subjects only. Diabetes type and treatment
      were unrelated. In those without diabetes, greater insulin resistance had a
      small, nonsignificant association with lower SHBG and higher free testosterone.
      CONCLUSIONS: SHBG and total testosterone appear to be higher in male children and
      young adults with diabetes compared with nondiabetic male siblings, which is
      apparently related to the absence of endogenous insulin. This may have
      implications for sex hormone-dependent processes across the lifespan in male
      individuals diagnosed with diabetes as children.

PMID- 18346990
TI  - Serum adiponectin and progression of diabetic nephropathy in patients with type 1
      diabetes.
AB  - OBJECTIVE: The purpose of this study was to elucidate whether serum adiponectin
      is associated with progression of diabetic nephropathy in type 1 diabetic
      patients. RESEARCH DESIGN AND METHODS: This was a prospective follow-up study as
      a part of the nationwide Finnish Diabetic Nephropathy Study; 1,330 type 1
      diabetic patients were followed for 5.0 +/- 2.2 years. Patients were divided at
      baseline into three groups according to their urinary albumin excretion rate
      (AER) in three consecutive overnight or 24-h urine collections: 818 patients with
      normoalbuminuria (AER <20 microg/min), 216 patients with microalbuminuria (20
      microg/min <or= AER < 200 microg/min), and 296 patients with macroalbuminuria
      (AER >or=200 microg/min). Progression of albuminuria was the main outcome.
      Adiponectin was measured by a time-resolved immunofluorometric assay, and the
      values were log-transformed and adjusted for age, BMI, and sex before analysis.
      RESULTS: Progression either to the next albuminuria level or to end-stage renal
      disease (ESRD) occurred in 193 patients. No difference in adiponectin
      concentrations was observed between progressors and nonprogressors in patients
      with normoalbuminuria or microalbuminuria. In the patients with macroalbuminuria,
      progression to ESRD was associated with higher adiponectin in the entire group
      (23.4 +/- 17.1 vs. 16.0 +/- 8.5 mg/l, P < 0.001) and in men (P < 0.001) and women
      (P < 0.001) separately. Progression to ESRD was also associated with systolic
      blood pressure, insulin dose, A1C, serum cholesterol, serum triglycerides, AER,
      and estimated glomerular filtration rate (eGFR). When these covariates were
      inserted in a Cox regression analysis, A1C, triglycerides, eGFR, and adiponectin
      were significantly associated with progression from macroalbuminuria.
      CONCLUSIONS: Increased serum adiponectin levels predict the progression from
      macroalbuminuria to ESRD in type 1 diabetic patients.

PMID- 18346992
TI  - Liver enzymes and incident diabetes: findings from the European Prospective
      Investigation into Cancer and Nutrition (EPIC)-Potsdam Study.
AB  - OBJECTIVE: We sought to examine the association between plasma concentrations of
      liver enzymes gamma-glutamyltransferase (GGT) and alanine transaminase (ALT) and
      incident diabetes, prospectively. RESEARCH DESIGN AND METHODS: We conducted a
      case-cohort analysis of data from participants mainly aged 35-65 years in the
      European Prospective Investigation into Cancer and Nutrition-Potsdam Study. The
      analytic sample included 787 participants with incident diabetes and 2,224
      participants without diabetes. RESULTS: Concentrations of GGT and ALT were
      significantly associated with incident diabetes after extensive adjustment.
      Compared with participants in the lowest quintile of GGT, the adjusted hazard
      ratios for increasing quintiles were 1.13 (95% CI 0.66-1.93), 1.67 (1.01-2.77),
      2.77 (1.71-4.49), and 2.67 (1.63-4.37), respectively (P for linear trend <0.001).
      Compared with participants in the lowest quintile of ALT, the adjusted hazard
      ratios for incident diabetes were 0.93 (0.56-1.53) for quintile 2, 1.28 (0.83
      1.96) for quintile 3, 1.35 (0.88-2.07) for quintile 4, and 1.93 (1.27-2.92) for
      quintile 5 (P for linear trend = 0.002). The magnitude of the associations were
      higher among men than women for GGT (P = 0.004) but did not differ significantly
      between men and women for ALT (P = 0.307). CONCLUSIONS: Concentrations of GGT and
      ALT were significant predictors of incident diabetes in this study, even at
      concentrations still considered to be within the normal range.

PMID- 18346993
TI  - Diabetic retinopathy: more patients, less laser: a longitudinal population-based
      study in Tayside, Scotland.
AB  - OBJECTIVE: We aim to correlate the incidence of diabetic retinopathy and
      maculopathy requiring laser treatment with the control of risk factors in the
      diabetic population of Tayside, Scotland, for the years 2001-2006. RESEARCH
      DESIGN AND METHODS: Retinal laser treatment, retinal screening, and diabetes care
      databases were linked for calendar years 2001-2006. Primary end points were the
      numbers of patients undergoing first or any laser treatment for diabetic
      retinopathy or maculopathy. Mean A1C and blood pressure and retinal screening
      rates were followed over the study period. RESULTS: Over 6 years, the number of
      patients with diabetes in Tayside increased from 9,694 to 15,207 (57% increase).
      The number of patients receiving laser treatment decreased from 222 to 138 and
      first laser treatments decreased from 100 (1.03% of diabetic population) to 56
      (0.37%). The number of patients with type 2 diabetes treated for maculopathy
      decreased from 180 in 2001 to 103 in 2006 (43% reduction, P = 0.03). Mean A1C
      decreased for type 1 and type 2 diabetic populations (P < 0.01) and a reduction
      in blood pressure was observed in type 2 diabetic patients (P < 0.01). The number
      of patients attending annual digital photographic retinopathy screening increased
      from 3,012 to 11,932. CONCLUSIONS: Laser treatment for diabetic maculopathy in
      type 2 diabetic patients has decreased in Tayside over a six-year period, despite
      an increased prevalence of diabetes and increased screening effort. We propose
      that earlier identification of type 2 diabetes and improved risk factor control
      has reduced the incidence of maculopathy severe enough to require laser
      treatment.

PMID- 18346994
TI  - Characterization of sperm chromatin quality in testicular cancer and Hodgkin's
      lymphoma patients prior to chemotherapy.
AB  - BACKGROUND: Although the incidences of testicular cancer and Hodgkin's lymphoma
      have increased in young men over the past decade, combination chemotherapy has
      improved survival. As fertility is of importance to these patients,
      characterization of sperm chromatin structure is needed. We assessed sperm
      chromatin in testicular cancer and Hodgkin's lymphoma patients prior to
      chemotherapy, in comparison with control community and idiopathic infertile
      volunteers. METHODS: DNA damage was assessed with the sperm chromatin structure
      assay (SCSA), terminal deoxynucleotidyl transferase-mediated dUTP nick end
      labeling (TUNEL) and comet assays; reactive thiols (SH) and DNA compaction were
      determined with the monobromobimane (mBBr) and chromomycin A3 (CMA3) assays,
      respectively. RESULTS: Both testicular cancer (37%) and Hodgkin's lymphoma (81%)
      patients had normospermic samples with increased DNA damage, compared with
      controls. Cancer patients also had higher reactive thiols and CMA3 staining,
      indicating low DNA compaction. CONCLUSIONS: Sperm DNA integrity and compaction
      were affected in testicular cancer and Hodgkin's lymphoma patients prior to
      chemotherapy. Although SCSA, TUNEL and comet assays all detected DNA damage, the
      latter was optimal for use in cancer patients. A combination of the comet assay
      with tests that evaluate sperm DNA compaction, such as flow cytometry-based CMA3
      and mBBr assays, is a reliable strategy to characterize sperm chromatin quality
      in cancer patients at the time of sperm banking.

PMID- 18346995
TI  - Gene expression profiling of human oocytes following in vivo or in vitro
      maturation.
AB  - BACKGROUND: Immature human oocytes matured in vitro, particularly those from
      gonadotrophin stimulated ovaries, are developmentally incompetent when compared
      with oocytes matured in vivo. This developmental incompetence has been explained
      as poor oocyte cytoplasmic maturation without any determination of the likely
      molecular basis of this observation. METHODS: Replicate whole human genome arrays
      were generated for immature and mature oocytes (matured in vivo and in vitro,
      prior to exposure to sperm) recovered from women undertaking gonadotrophin
      treatment for assisted reproduction. RESULTS: More than 2000 genes were
      identified as expressed at more than 2-fold higher levels in oocytes matured in
      vitro than those matured in vivo (P < 0.05, range 4.98 x 10(-2) -2.22 x 10(-4))
      and 162 of these are expressed at 10-fold or greater levels (P < 0.05, range 4.98
      x 10(-2)-1.38 x 10(-3)). Many of these genes are involved in transcription, the
      cell cycle and its regulation, transport and cellular protein metabolism.
      CONCLUSIONS: Global gene expression profiling using microarrays and
      bioinformatics analysis has provided a molecular basis for differences in the
      developmental competence of oocytes matured in vitro compared with in vivo. The
      over-abundance of transcripts identified in immature germinal vesicle stage
      oocytes recovered from gonadotrophin stimulated cycles and matured in vitro is
      probably due to dysregulation in either gene transcription or post
      transcriptional modification of genes. Either mechanism would result in an
      incorrect temporal utilization of genes which may culminate in developmental
      incompetence of any embryos derived from these oocytes.

PMID- 18346996
TI  - A safety and efficacy study of a resorbable hydrogel for reduction of post
      operative adhesions following myomectomy.
AB  - BACKGROUND: This multicenter, randomized, single-blind study assessed the safety
      and efficacy of a resorbable hydrogel ('Hydrogel') for the reduction of post
      operative adhesion formation following myomectomy. METHODS: Women (n = 71) who
      were undergoing laparoscopic (67.6%) or laparotomic myomectomy were randomized
      (2:1) to Hydrogel (sprayed over surgically treated areas prior to wound closure,
      n = 48) or to control (standard care, n = 23). Patients (38 Hydrogel, 20 control)
      returned 8-10 weeks later for a second look. Adhesions were graded using a
      modified American Fertility Society (mAFS) scoring method. The primary efficacy
      measure was the posterior uterus mAFS score. RESULTS: For Hydrogel and control
      patients, respectively, mean +/- SD mAFS scores were 0.5 +/- 1.4 and 0.0 +/- 0.0
      at baseline, and 1.1 +/- 1.9 and 2.6 +/- 2.2 at the second look. Similarly, mean
      changes from baseline were 0.8 +/- 2.0 and 2.6 +/- 2.2 (P = 0.01); 95% confidence
      intervals for these mean changes were (0.16-1.44) and (1.64-3.56). Adverse events
      were reported by 9.6 and 17.4% of Hydrogel and control patients, respectively. No
      intra-abdominal infections or post-operative site infections were reported.
      CONCLUSIONS: This 71-patient study provides the first clinical evidence of the
      safety and efficacy of Hydrogel for the reduction of adhesions following
      myomectomy. The ClinicalTrials.gov Identifier is NCT00562471.

PMID- 18346998
TI  - Orbitofrontal cortex response to angry faces in men with histories of suicide
      attempts.
AB  - OBJECTIVE: The authors sought to elucidate the functional neural basis of the
      neurobiological abnormalities underlying the vulnerability to suicidal behavior.
      METHOD: Event-related functional MRI was used to measure neural activity in
      response to angry and happy versus neutral faces. Thirteen currently euthymic men
      with a history of major depressive disorder and suicidal behavior were compared
      with 14 currently euthymic men with a history of major depressive disorder but
      not of suicidal acts (affective comparison subjects) and 16 healthy male
      comparison subjects. RESULTS: Relative to affective comparison subjects, suicide
      attempters showed greater activity in the right lateral orbitofrontal cortex
      (Brodmann's area 47) and decreased activity in the right superior frontal gyrus
      (area 6) in response to prototypical angry versus neutral faces, greater activity
      in the right anterior cingulate gyrus (area 32 extending to area 10) to mild
      happy versus neutral faces, and greater activity in the right cerebellum to mild
      angry versus neutral faces. However, activation in these frontal regions did not
      differ between healthy individuals and either patient group. Relative to healthy
      comparison subjects, both patient groups showed reduced activity in the right
      cerebellum to neutral faces and to mild happy versus neutral faces. CONCLUSIONS:
      Suicide attempters were distinguished from nonsuicidal patients by responses to
      angry and happy faces that may suggest increased sensitivity to others'
      disapproval, higher propensity to act on negative emotions, and reduced attention
      to mildly positive stimuli. These patterns of neural activity and cognitive
      processes may represent vulnerability markers of suicidal behavior in men with a
      history of depression.

PMID- 18346997
TI  - Neurobiology of aggression and violence.
AB  - Acts of violence account for an estimated 1.43 million deaths worldwide annually.
      While violence can occur in many contexts, individual acts of aggression account
      for the majority of instances. In some individuals, repetitive acts of aggression
      are grounded in an underlying neurobiological susceptibility that is just
      beginning to be understood. The failure of "top-down" control systems in the
      prefrontal cortex to modulate aggressive acts that are triggered by anger
      provoking stimuli appears to play an important role. An imbalance between
      prefrontal regulatory influences and hyper-responsivity of the amygdala and other
      limbic regions involved in affective evaluation are implicated. Insufficient
      serotonergic facilitation of "top-down" control, excessive catecholaminergic
      stimulation, and subcortical imbalances of glutamatergic/gabaminergic systems as
      well as pathology in neuropeptide systems involved in the regulation of
      affiliative behavior may contribute to abnormalities in this circuitry. Thus,
      pharmacological interventions such as mood stabilizers, which dampen limbic
      irritability, or selective serotonin reuptake inhibitors (SSRIs), which may
      enhance "top-down" control, as well as psychosocial interventions to develop
      alternative coping skills and reinforce reflective delays may be therapeutic.

PMID- 18346999
TI  - G72 and its association with major depression and neuroticism in large population
      based groups from Germany.
AB  - OBJECTIVE: G72 is among the most frequently replicated vulnerability genes for
      schizophrenia and bipolar disorder. The authors previously found identical
      haplotypes of markers M23 and M24 to be associated with schizophrenia, bipolar
      disorder, and panic disorder. Given both the well-recognized familial clustering
      across these disorders and recent linkage findings implicating the region
      harboring G72 in the etiology of major depression and panic disorder, we can
      hypothesize that G72 should also be involved in the etiology of major depression.
      Neuroticism, measuring trait anxiety, may be the endophenotypic link underlying
      genetic associations with G72 across diagnostic boundaries. The authors tested
      whether the previously observed risk haplotypes are also associated with major
      depression and neuroticism. METHOD: The authors performed a standard haplotype
      analysis in a group of 500 major depression patients and 1,030 population-based
      comparison subjects. The authors also performed an exploratory analysis on 10
      additional G72 markers using a novel haplotype-sharing approach. They performed a
      quantitative trait haplotype analysis in an independent group of 907 individuals
      phenotyped for neuroticism. RESULTS: The previously identified M23-M24 risk
      haplotype was significantly associated with major depression and high levels of
      neuroticism. The haplotype-sharing analysis also implicated the same region,
      whereas more proximal markers showed no association with major depression.
      CONCLUSIONS: This is the first study to the authors' knowledge to implicate the
      G72 locus in the etiology of major depression and neuroticism. The results
      strengthen the notion of a genetic overlap between diagnoses, commonly
      conceptualized as distinct entities. Neuroticism may constitute the common
      underlying endophenotypic link.

PMID- 18347000
TI  - The other-race effect in face processing among African American and Caucasian
      individuals with schizophrenia.
AB  - OBJECTIVE: Studies of emotion recognition abilities in schizophrenia show greater
      impairment for non-Caucasians with schizophrenia compared with Caucasians. These
      studies, however, included only Caucasian faces as stimuli. There is evidence
      from healthy individuals for a performance disadvantage on face memory and
      emotion recognition when processing faces from a different ethnicity. The authors
      sought to measure the "other-race effect" in schizophrenia, which could account
      for previous findings and provide information about sensitivity to such social
      cues in patients. METHOD: The study included 540 participants from four groups:
      African Americans with schizophrenia (N=135), Caucasians with schizophrenia
      (N=135), African American community comparison subjects (N=135), and Caucasian
      community comparison subjects (N=135). All participants completed face
      recognition and facial emotion identification tasks that included both Caucasian
      and African American faces as stimuli. RESULTS: Although comparison participants
      performed better than individuals with schizophrenia across all tasks, both
      comparison participants and participants with schizophrenia exhibited a strong
      and significant other-race effect for face memory and emotion recognition. The
      magnitude of the other-race effect did not differ between these two groups.
      CONCLUSIONS: These findings reveal an intact other-race effect in patients with
      schizophrenia and highlight a methodological concern in the measurement of face
      processing abilities in schizophrenia, namely, that findings of greater
      impairment in African American patients are spurious when Caucasian faces are
      used as stimuli. Despite overall impairments in face memory and emotion
      recognition, the presence of a normative other-race effect in schizophrenia may
      reflect typical experiences with faces during development.

PMID- 18347001
TI  - Increased anxiety during anticipation of unpredictable but not predictable
      aversive stimuli as a psychophysiologic marker of panic disorder.
AB  - OBJECTIVE: Predictability is a fundamental modulator of anxiety in that the
      ability to predict aversive events mitigates anxious responses. In panic
      disorder, persistent symptoms of anxiety are caused by anticipation of the next
      uncued (unpredictable) panic attack. The authors tested the hypothesis that
      elevated anxious reactivity, specifically toward unpredictable aversive events,
      is a psychophysiological correlate of panic disorder. METHOD: Participants were
      exposed to one condition in which predictable aversive stimuli were signaled by a
      cue, a second condition in which aversive stimuli were administered
      unpredictably, and a third condition in which no aversive stimuli were
      anticipated. Startle was used to assess anxious responses to cues and contexts.
      RESULTS: Relative to healthy comparison subjects, patients with panic disorder
      displayed equivalent levels of fear-potentiated startle to the threat cue but
      elevated startle potentiation in the context of the unpredictable condition.
      CONCLUSIONS: Patients with panic disorder are overly sensitive to unpredictable
      aversive events. This vulnerability could be either a premorbid trait marker of
      the disorder or an acquired condition caused by the experience of uncued panic
      attacks. As a premorbid trait, vulnerability to unpredictability could be
      etiologically related to panic disorder by sensitizing an individual to danger,
      ultimately leading to intense fear/alarm responses to mild threats. As an
      acquired characteristic, such vulnerability could contribute to the maintenance
      and worsening of panic disorder symptoms by increasing anticipatory anxiety.

PMID- 18347002
TI  - Association of the neurotrophic tyrosine kinase receptor 3 (NTRK3) gene and
      childhood-onset mood disorders.
AB  - OBJECTIVE: Genome scans have revealed significant evidence for linkage of
      depression to chromosome 15q25.3-q26.2. The gene for neurotrophic tyrosine kinase
      receptor 3 (NTRK3), the receptor for neurotrophin-3 (trkC) and a key gene in
      neurotrophin signaling, is located within this region and, given evidence for
      synaptic plasticity as a mechanism in mood disorders, was considered a prime
      candidate. The authors investigated NTRK3 as a susceptibility gene for childhood
      onset mood disorders. METHOD: The study sample consisted of 603 families with 723
      affected children and adolescents diagnosed with a mood disorder with onset of
      the first episode by age 15. The authors genotyped 18 polymorphic markers across
      the NTRK3 gene in this sample and tested for association. RESULTS: Results
      identified significant evidence for association for five of the markers using the
      transmission disequilibrium test. Four of the five markers were located in a
      region of strong linkage disequilibrium and were highly correlated. Haplotype
      results provided significant evidence for association to haplotypes composed of
      markers located in two haplotype blocks. CONCLUSIONS: The results for NTRK3 as
      well as the authors' previous finding for association to brain-derived
      neurotrophic factor in this sample support synaptic plasticity as a mechanism
      contributing to mood disorders that begin during childhood and adolescence and
      specifically implicate the NTRK3 gene as a contributing factor in the 15q-linked
      region.

PMID- 18347003
TI  - 8-year follow-up of patients treated for borderline personality disorder:
      mentalization-based treatment versus treatment as usual.
AB  - OBJECTIVE: This study evaluated the effect of mentalization-based treatment by
      partial hospitalization compared to treatment as usual for borderline personality
      disorder 8 years after entry into a randomized, controlled trial and 5 years
      after all mentalization-based treatment was complete. METHOD: Interviewing was by
      research psychologists blind to original group allocation and structured review
      of medical notes of 41 patients from the original trial. Multivariate analysis of
      variance, chi-square, univariate analysis of variance, and nonparametric Mann
      Whitney statistics were used to contrast the two groups depending on the
      distribution of the data. RESULTS: Five years after discharge from mentalization
      based treatment, the mentalization-based treatment by partial hospitalization
      group continued to show clinical and statistical superiority to treatment as
      usual on suicidality (23% versus 74%), diagnostic status (13% versus 87%),
      service use (2 years versus 3.5 years of psychiatric outpatient treatment), use
      of medication (0.02 versus 1.90 years taking three or more medications), global
      function above 60 (45% versus 10%), and vocational status (employed or in
      education 3.2 years versus 1.2 years). CONCLUSIONS: Patients with 18 months of
      mentalization-based treatment by partial hospitalization followed by 18 months of
      maintenance mentalizing group therapy remain better than those receiving
      treatment as usual, but their general social function remains impaired.

PMID- 18347004
TI  - The "other" signaling of trastuzumab: antibodies are immunocompetent drugs.

PMID- 18347005
TI  - Immunoglobulin G fragment C receptor polymorphisms and clinical efficacy of
      trastuzumab-based therapy in patients with HER-2/neu-positive metastatic breast
      cancer.
AB  - PURPOSE: The anti-HER-2/neu monoclonal antibody trastuzumab has been shown to
      engage both activatory (fragment C receptor [Fc gamma R]IIIa; Fc gamma RIIa) and
      inhibitory (Fc gamma RIIb) antibody receptors and Fc gamma R polymorphisms have
      been identified that may affect the antibody-dependent cell-mediated cytotoxicity
      (ADCC) of natural-killer cells/monocytes. In this study, we tested whether Fc
      gamma R polymorphisms are associated with clinical outcome of patients with
      breast cancer who received trastuzumab. PATIENTS AND METHODS: Fifty-four
      consecutive patients with HER-2/neu-amplified breast cancer receiving trastuzumab
      plus taxane for metastatic disease were evaluated for genotype for the Fc gamma
      RIIIa-158 valine(V)/phenylalanine(F), Fc gamma RIIa-131 histidine(H)/arginine(R),
      and Fc gamma RIIb-232 isoleucine(I)/threonine(T) polymorphisms. Trastuzumab
      mediated ADCC of patients' peripheral blood mononuclear cells (PBMCs) was
      measured by chromium-51 release using a HER-2/neu-expressing human breast cancer
      cell line as a target. Controls comprised thirty-four patients treated with
      taxane alone. RESULTS: Our population was in Hardy-Weinberg equilibrium except
      for the Fc gamma RIIb polymorphism. The Fc gamma RIIIa-158 V/V genotype was
      significantly correlated with objective response rate (ORR) and progression-free
      survival (PFS). Also, there was trend significance in ORR and PFS for the Fc
      gamma RIIa-131 H/H genotype. The combination of the two favorable genotypes (VV
      and/or H/H) was independently associated with better ORR and PFS compared with
      the other combinations. The ADCC analysis showed that V/V and/or H/H PBMCs had a
      significantly higher trastuzumab-mediated cytotoxicity than PBMCs harboring
      different genotypes. CONCLUSION: These data support for the first time the
      hypothesis that Fc gamma R-mediated ADCC plays an important role in the clinical
      effect of trastuzumab. Prospective studies are needed to confirm the role of Fc
      gamma R polymorphisms in predicting clinical outcome of patients with breast
      cancer treated with trastuzumab-based therapy.

PMID- 18347006
TI  - Risk of subsequent solid tumors after non-Hodgkin's lymphoma: effect of
      diagnostic age and time since diagnosis.
AB  - PURPOSE: Quantitative data on subsequent cancers after primary cancers provide
      information on treatment-related risks on second cancers, with implications for
      therapeutic adverse effects and human susceptibility in general. Quantitative
      data on solid tumors are limited. We focus on survivors of non-Hodgkin's lymphoma
      (NHL) because the disease is diagnosed at a wide range of ages and treated
      uniformly primarily with chemotherapy. PATIENTS AND METHODS: The nationwide
      Swedish Family-Cancer Database included 11.5 million individuals whose cancers
      were retrieved from the Swedish Cancer Registry. Standardized incidence ratios
      (SIRs) were calculated for subsequent neoplasms among 28,131 patients with NHL.
      RESULTS: The SIR for solid tumors after NHL was 1.65 (2,290 patients) and that
      for lymphohematopoietic neoplasms was 5.36 (369 patients). Among the 25 most
      common solid tumors, the SIRs were increased for all but nine sites; the highest
      SIR (40.8) was observed for spinal meningioma. The SIRs for solid tumors declined
      in an age-dependent manner from 4.52 in diagnostic age younger than 20 years to
      1.12 in diagnostic age 70+ years. In the most common patient groups, the SIRs for
      solid tumors increased up to 30 years after NHL diagnosis. Because of the high
      incidence of solid tumors in these age groups, they contributed the largest
      numbers of therapy-related cases. CONCLUSION: These data indicate that age at
      treatment determines both the magnitude of the initial relative risk and the time
      dependent modulation of the response. Therapy-related damage persists at least 30
      years and its toll of solid tumors is largest 21 to 30 years after diagnosis.

PMID- 18347007
TI  - Phase II study of sunitinib malate, an oral multitargeted tyrosine kinase
      inhibitor, in patients with metastatic breast cancer previously treated with an
      anthracycline and a taxane.
AB  - PURPOSE: Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that
      inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived
      growth factor receptor, stem cell factor receptor (KIT), and colony-stimulating
      factor-1 receptor. This phase II, open-label, multicenter study evaluated
      sunitinib monotherapy in patients with metastatic breast cancer (MBC). PATIENTS
      AND METHODS: Sixty-four patients previously treated with an anthracycline and a
      taxane received sunitinib 50 mg/d in 6-week cycles (4 weeks on, then 2 weeks off
      treatment). The primary end point was objective response rate. Plasma samples
      were obtained for pharmacokinetic and biomarker analysis. RESULTS: Seven patients
      achieved a partial response (median duration, 19 weeks), giving an overall
      response rate of 11%. Three additional patients (5%) maintained stable disease
      for >or= 6 months. Median time to progression and overall survival were 10 and 38
      weeks, respectively. Notably, responses occurred in triple negative tumors and
      HER2-positive, trastuzumab-treated patients. Thirty-three patients (52%) required
      dose interruption during >or= 1 cycle, and 25 patients required dose reduction
      (39%). Thirty-six patients (56%) had dose modifications due to adverse events
      (AEs). Treatment was associated with increases in plasma VEGF and decreases in
      soluble VEGFRs and KIT. The most common AEs were fatigue, nausea, diarrhea,
      mucosal inflammation, and anorexia. Most AEs were mild to moderate (grade 1 to 2)
      in severity and were effectively managed with dose delays or reductions.
      CONCLUSION: Sunitinib is active in patients with heavily pretreated MBC. Most AEs
      were of mild-to-moderate severity and manageable with supportive treatment and/or
      dose modification. Further studies in breast cancer are warranted.

PMID- 18347008
TI  - Phase I study of recombinant interleukin-21 in patients with metastatic melanoma
      and renal cell carcinoma.
AB  - PURPOSE: A phase I study of patients with metastatic malignant melanoma (MM) and
      renal cell carcinoma (RCC) evaluated the safety and maximum tolerated dose (MTD),
      pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of
      recombinant human interleukin-21 (rIL-21). PATIENTS AND METHODS: Patients who had
      one or fewer prior systemic treatments for metastatic MM or RCC were treated with
      rIL-21 administered for two 5-day cycles on days 1 through 5 and 15 through 19 of
      a treatment course; rIL-21 was administered by rapid intravenous infusion in an
      outpatient setting. Cohorts of patients received doses ranging from 3 to 100
      microg/kg/dose, and an expanded cohort was treated at the MTD. Patients with
      stable disease (SD) or better could receive additional treatment cycles. RESULTS:
      Forty-three patients were treated (24 MM; 19 RCC), including 28 in the expanded
      cohort. Dose-limiting toxicities consisted primarily of transient grade 3
      laboratory abnormalities. The MTD was estimated to be 30 microg/kg. The most
      common adverse events included flu-like symptoms, pruritus, and rash. Twelve
      patients received up to five additional two-cycle courses of treatment without
      cumulative toxicity, except for one patient with reversible grade 4
      hepatotoxicity. Serum concentrations of rIL-21 increased in a dose-proportional
      manner. Dose-dependent increases in soluble CD25 reflected lymphocyte activation.
      Antitumor activity was observed in both MM (one complete response and 11 SD) and
      RCC (four partial responses, 13 SD). CONCLUSION: Outpatient therapy with rIL-21
      at 30 microg/kg was well tolerated, had dose-dependent pharmacokinetics and
      pharmacodynamics, and was associated with antitumor activity in patients with MM
      and RCC.

PMID- 18347009
TI  - The novel small molecule drug Rabeximod is effective in reducing disease severity
      of mouse models of autoimmune disorders.
AB  - OBJECTIVES: Autoimmune diseases such as rheumatoid arthritis (RA) and multiple
      sclerosis (MS) affect a relatively large portion of the population, leading to
      severe disability if left untreated. Even though pharmaceutics targeting the
      immune system have revolutionised the therapy of these diseases, there is still a
      need for novel, more effective therapeutic substances. One such substance is the
      new chemical entity 9-chloro-2,3 dimethyl-6-(N,N-dimthylamino-2-oxoethyl)-6H
      indolo [2,3-b] quionoxaline, Rabeximod, currently being investigated for
      efficiency in treatment of human RA. In this study we aimed to evaluate Rabeximod
      as a treatment for autoimmune diseases, using animal models. METHODS: In the
      present investigation we have evaluated Rabeximod as a treatment for autoimmune
      diseases using mouse models of RA and MS, ie, collagen-induced arthritis,
      collagen antibody induced arthritis and experimental autoimmune
      encephalomyelitis. RESULTS: Rabeximod efficiently prevented arthritis and
      encephalomyelitis in mice. In addition, this effect correlated to the timepoint
      when cells migrate into the joints. CONCLUSIONS: We conclude that Rabeximod
      reduces disease severity in animal models of autoimmunity and should be
      considered as a new therapeutic substance for MS and RA.

PMID- 18347010
TI  - Regulation of energy substrate utilization and hepatic insulin sensitivity by
      phosphatidylcholine transfer protein/StarD2.
AB  - Phosphatidylcholine transfer protein (PC-TP, also known as StarD2) is a highly
      specific intracellular lipid binding protein with accentuated expression in
      oxidative tissues. Here we show that decreased plasma concentrations of glucose
      and free fatty acids in fasting PC-TP-deficient (Pctp(-/-)) mice are attributable
      to increased hepatic insulin sensitivity. In hyperinsulinemic-euglycemic clamp
      studies, Pctp(-/-) mice exhibited profound reductions in hepatic glucose
      production, gluconeogenesis, glycogenolysis, and glucose cycling. These changes
      were explained in part by the lack of PC-TP expression in liver per se and in
      part by marked alterations in body fat composition. Reduced respiratory quotients
      in Pctp(-/-) mice were indicative of preferential fatty acid utilization for
      energy production in oxidative tissues. In the setting of decreased hepatic fatty
      acid synthesis, increased clearance rates of dietary triglycerides and increased
      hepatic triglyceride production rates reflected higher turnover in Pctp(-/-)
      mice. Collectively, these data support a key biological role for PC-TP in the
      regulation of energy substrate utilization.

PMID- 18347011
TI  - Suppression of hepatic glucose production by human neutrophil alpha-defensins
      through a signaling pathway distinct from insulin.
AB  - In this study, we tested the hypothesis that human neutrophil alpha-defensins
      (HNPs) inhibit hepatic glucose production through a signaling pathway distinct
      from insulin. The effect of HNP-1 on fasting blood glucose levels and the
      expression of hepatic gluconeogenic genes was first examined. Using
      hyperinsulinemic-euglycemic clamps, we determined the effect of HNP-1 on
      endogenous glucose production, hepatic expression of key gluconeogenic genes and
      glucose uptake in skeletal muscle in Zucker diabetic fatty rats. In isolated
      primary hepatocytes, we studied the effect of HNP-1 and -2 on glucose production,
      expression of gluconeogenic genes, and phosphorylation of Akt, c-Src, and FoxO1.
      Our results show that HNP-1 reduced blood glucose levels of both normal mice and
      Zucker diabetic fatty rats predominantly through suppression of hepatic glucose
      production. HNPs inhibited glycogenolysis and gluconeogenesis in isolated
      hepatocytes. HNPs also suppressed expression of key gluconeogenic genes including
      phosphoenoylpyruvate carboxyl kinase and glucose-6-phosphatase. To investigate
      the mechanism, we found that HNPs stimulated phosphorylation of Akt and FoxO1
      without activating IRS1. Nevertheless, HNPs activated c-Src. Blockade of c-Src
      activity with either a chemical inhibitor PP2 or an alternative inhibitor CSK
      prevented the inhibitory effect of HNPs on gluconeogenesis. Together, our results
      support the hypothesis that HNPs can suppress hepatic glucose production through
      an intracellular mechanism distinct from the classical insulin signaling pathway.

PMID- 18347012
TI  - RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates
      noncentrosomal microtubules.
AB  - Microtubule spindle assembly in mitosis is stimulated by Ran.GTP, which is
      generated along condensed chromosomes by the guanine nucleotide exchange factor
      (GEF) RCC1. This relationship suggests that similar activities might modulate
      other microtubule structures. Interphase microtubules usually extend from the
      centrosome, although noncentrosomal microtubules function in some differentiated
      cells, including megakaryocytes. In these cells, platelet biogenesis requires
      massive mobilization of microtubules in the cell periphery, where they form
      proplatelets, the immediate precursors of platelets, in the apparent absence of
      centrioles. Here we identify a cytoplasmic Ran-binding protein, RanBP10, as a
      factor that binds beta-tubulin and associates with megakaryocyte microtubules.
      Unexpectedly, RanBP10 harbors GEF activity toward Ran. A point mutation in the
      candidate GEF domain abolishes exchange activity, and our results implicate
      RanBP10 as a localized cytoplasmic Ran-GEF. RNA interference-mediated loss of
      RanBP10 in cultured megakaryocytes disrupts microtubule organization. These
      results lead us to propose that spatiotemporally restricted generation of
      cytoplasmic Ran.GTP may influence organization of the specialized microtubules
      required in thrombopoiesis and that RanBP10 might serve as a molecular link
      between Ran and noncentrosomal microtubules.

PMID- 18347013
TI  - The lymphotoxin-beta receptor is an upstream activator of NF-kappaB-mediated
      transcription in melanoma cells.
AB  - The pleiotropic transcription factor nuclear factor-kappaB (NF-kappaB (p50/p65))
      regulates the transcription of genes involved in the modulation of cell
      proliferation, apoptosis, and oncogenesis. Furthermore, a host of solid and
      hematopoietic tumor types exhibit constitutive activation of NF-kappaB (Basseres,
      D. S., and Baldwin, A. S. (2006) 25, 6817-6830). However, the mechanism for this
      constitutive activation of NF-kappaB has not been elucidated in the tumors. We
      have previously shown that NF-kappaB-inducing kinase (NIK) protein and its
      association with Inhibitor of kappaB kinase alphabeta are elevated in melanoma
      cells compared with their normal counterpart, leading to constitutive activation
      of NF-kappaB. Moreover, expression of dominant negative NIK blocked this base
      line NF-kappaB activity in melanoma cells. Of the three receptors that require
      NIK for activation of NF-kappaB, only the lymphotoxin-beta receptor (LTbeta-R) is
      expressed in melanoma. We show in this manuscript that for melanoma there is a
      strong relationship between expression of the LTbeta-R and constitutive NF-kappaB
      transcriptional activity. Moreover, we show that activation of the LTbeta-R can
      drive NF-kappaB activity to regulate gene expression that leads to enhanced cell
      growth. The inhibition by LTbeta-R shRNA resulted in decreased NF-kappaB promoter
      activity, decreased growth, and decreased invasiveness as compared with control.
      These results indicate that the LTbeta-R constitutively induces NF-kappaB
      activation, and this event may be associated with autonomous growth of melanoma
      cells.

PMID- 18347014
TI  - Dematin and adducin provide a novel link between the spectrin cytoskeleton and
      human erythrocyte membrane by directly interacting with glucose transporter-1.
AB  - Dematin and adducin are actin-binding proteins located at the spectrin-actin
      junctions, also called the junctional complex, in the erythrocyte membrane. Here
      we propose a new model whereby dematin and adducin link the junctional complex to
      human erythrocyte plasma membrane. Using a combination of surface labeling,
      immunoprecipitation, and vesicle proteomics approaches, we have identified
      glucose transporter-1 as the receptor for dematin and adducin in the human
      erythrocyte membrane. This finding is the first description of a transmembrane
      protein that binds to dematin and adducin, thus providing a rationale for the
      attachment of the junctional complex to the lipid bilayer. Because homologues of
      dematin, adducin, and glucose transporter-1 exist in many non-erythroid cells, we
      propose that a conserved mechanism may exist that couples sugar and other related
      transporters to the actin cytoskeleton.

PMID- 18347015
TI  - Roles of Pofut1 and O-fucose in mammalian Notch signaling.
AB  - Mammalian Notch receptors contain 29-36 epidermal growth factor (EGF)-like
      repeats that may be modified by protein O-fucosyltransferase 1 (Pofut1), an
      essential component of the canonical Notch signaling pathway. The Drosophila
      orthologue Ofut1 is proposed to function as both a chaperone required for stable
      cell surface expression of Notch and a protein O-fucosyltransferase. Here we
      investigate these dual roles of Pofut1 in relation to endogenous Notch receptors
      of Chinese hamster ovary and murine embryonic stem (ES) cells. We show that
      fucosylation-deficient Lec13 Chinese hamster ovary cells have wild type levels of
      Pofut1 and cell surface Notch receptors. Nevertheless, they have reduced binding
      of Notch ligands and low levels of Delta1- and Jagged1-induced Notch signaling.
      Exogenous fucose but not galactose rescues both ligand binding and Notch
      signaling. Murine ES cells lacking Pofut1 also have wild type levels of cell
      surface Notch receptors. However, Pofut1-/- ES cells do not bind Notch ligands or
      exhibit Notch signaling. Although overexpression of fucosyltransferase-defective
      Pofut1 R245A in Pofut1-/- cells partially rescues ligand binding and Notch
      signaling, this effect is not specific. The same rescue is achieved by an
      unrelated, inactive, endoplasmic reticulum glucosidase. Therefore, mammalian
      Notch receptors require Pofut1 for the generation of optimally functional Notch
      receptors, but, in contrast to Drosophila, Pofut1 is not required for stable cell
      surface expression of Notch. Importantly, we also show that, under certain
      circumstances, mammalian Notch receptors are capable of signaling in the absence
      of Pofut1 and O-fucose.

PMID- 18347016
TI  - The solution structures of two soybean calmodulin isoforms provide a structural
      basis for their selective target activation properties.
AB  - The intracellular calcium ion is one of the most important secondary messengers
      in eukaryotic cells. Ca(2+) signals are translated into physiological responses
      by EF-hand calcium-binding proteins such as calmodulin (CaM). Multiple CaM
      isoforms occur in plant cells, whereas only a single CaM protein is found in
      animals. Soybean CaM isoform 1 (sCaM1) shares 90% amino acid sequence identity
      with animal CaM (aCaM), whereas sCaM4 is only 78% identical. These two sCaM
      isoforms have distinct target-enzyme activation properties and physiological
      functions. sCaM4 is highly expressed during the self-defense reaction of the
      plant and activates the enzyme nitric-oxide synthase (NOS), whereas sCaM1 is
      incapable of activating NOS. The mechanism of selective target activation by
      plant CaM isoforms is poorly understood. We have determined high resolution NMR
      solution structures of Ca(2+)-sCaM1 and -sCaM4. These were compared with
      previously determined Ca(2+)-aCaM structures. For the N-lobe of the protein, the
      solution structures of Ca(2+)-sCaM1, -sCaM4, and -aCaM all closely resemble each
      other. However, despite the high sequence identity with aCaM, the C-lobe of
      Ca(2+)-sCaM1 has a more open conformation and consequently a larger hydrophobic
      target-protein binding pocket than Ca(2+)-aCaM or -sCaM4, the presence of which
      was further confirmed through biophysical measurements. The single Val-144 -->
      Met substitution in the C-lobe of Ca(2+)-sCaM1, which restores its ability to
      activate NOS, alters the structure of the C-lobe to a more closed conformation
      resembling Ca(2+)-aCaM and -sCaM4. The relationships between the structural
      differences in the two Ca(2+)-sCaM isoforms and their selective target activation
      properties are discussed.

PMID- 18347017
TI  - Characterization of Arabidopsis thaliana pinoresinol reductase, a new type of
      enzyme involved in lignan biosynthesis.
AB  - A lignan, lariciresinol, was isolated from Arabidopsis thaliana, the most widely
      used model plant in plant bioscience sectors, for the first time. In the A.
      thaliana genome database, there are two genes (At1g32100 and At4g13660) that are
      annotated as pinoresinol/lariciresinol reductase (PLR). The recombinant AtPLRs
      showed strict substrate preference toward pinoresinol but only weak or no
      activity toward lariciresinol, which is in sharp contrast to conventional PLRs of
      other plants that can reduce both pinoresinol and lariciresinol efficiently to
      lariciresinol and secoisolariciresinol, respectively. Therefore, we renamed
      AtPLRs as A. thaliana pinoresinol reductases (AtPrRs). The recombinant AtPrR2
      encoded by At4g13660 reduced only (-)-pinoresinol to (-)-lariciresinol and not
      (+)-pinoresinol in the presence of NADPH. This enantiomeric selectivity accords
      with that of other PLRs of other plants so far reported, which can reduce one of
      the enantiomers selectively, whatever the preferential enantiomer. In sharp
      contrast, AtPrR1 encoded by At1g32100 reduced both (+)- and (-)-pinoresinols to
      (+)- and (-)-lariciresinols efficiently with comparative k(cat)/K(m) values.
      Analysis of lignans and spatiotemporal expression of AtPrR1 and AtPrR2 in their
      functionally deficient A. thaliana mutants and wild type indicated that both
      genes are involved in lariciresinol biosynthesis. In addition, the analysis of
      the enantiomeric compositions of lariciresinol isolated from the mutants and wild
      type showed that PrRs together with a dirigent protein(s) are involved in the
      enantiomeric control in lignan biosynthesis. Furthermore, it was demonstrated
      conclusively for the first time that differential expression of PrR isoforms that
      have distinct selectivities of substrate enantiomers can determine enantiomeric
      compositions of the product, lariciresinol.

PMID- 18347018
TI  - Identification of a conserved Rac-binding site on NADPH oxidases supports a
      direct GTPase regulatory mechanism.
AB  - The NADPH oxidases (Noxs) are a family of superoxide-generating enzymes
      implicated in a variety of biological processes. Full activity of Nox1, -2, and 
      3 requires the action of a Rac GTPase. A direct regulatory interaction of Rac
      with Nox2 has been proposed as part of a two-step mechanism for regulating
      electron transfer during superoxide formation. Using truncation analysis of Rac
      binding to the cytoplasmic tail of Nox2, along with peptides derived from this
      region in cell-free assays, we identify a Rac interaction site within amino acids
      419-430 of Nox2. This region is required for binding Rac2 but not p47(phox) or
      p67(phox) cytosolic regulatory factors. A cell-permeant version of the peptide
      encompassing amino acids 419-430 specifically inhibits NADPH oxidase activation
      in intact human neutrophils. Mutational analysis of the putative Rac-binding site
      revealed specific residues, particularly Lys-421, Tyr-425, and Lys-426,
      individually required for Rac-dependent NADPH oxidase activity that are conserved
      in the Rac-regulated Nox1, Nox2, and Nox3 enzymes but not in Nox4 or Nox5.
      Mutation of the conserved residues in the Rac-binding site of Nox1 also result in
      the loss of Rac-dependent activity. Our data identify a functional Rac
      interaction site conserved in Rac-dependent Noxs and support a direct regulatory
      interaction of Rac GTPases to promote activation of these NADPH oxidases.

PMID- 18347019
TI  - Non-transferrin iron reduction and uptake are regulated by transmembrane
      ascorbate cycling in K562 cells.
AB  - K562 erythroleukemia cells import non-transferrin-bound iron (NTBI) by an
      incompletely understood process that requires initial iron reduction. The
      mechanism of NTBI ferrireduction remains unknown but probably involves
      transplasma membrane electron transport. We here provide evidence for a novel
      mechanism of NTBI reduction and uptake by K562 cells that utilizes transplasma
      membrane ascorbate cycling. Incubation of cells with dehydroascorbic acid, but
      not ascorbate, resulted in (i) accumulation of intracellular ascorbate that was
      blocked by the glucose transporter inhibitor, cytochalasin B, and (ii) subsequent
      release of micromolar concentrations of ascorbate into the external medium via a
      route that was sensitive to the anion channel inhibitor, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonate. Ascorbate-deficient control cells
      demonstrated low levels of ferric citrate reduction. However, incubation of the
      cells with dehydroascorbic acid resulted in a dose-dependent stimulation of both
      iron reduction and uptake from radiolabeled [(55)Fe]ferric citrate. This
      stimulation was abrogated by ascorbate oxidase treatment, suggesting dependence
      on direct chemical reduction by ascorbate. These results support a novel model of
      NTBI reduction and uptake by K562 cells in which uptake is preceded by reduction
      of iron by extracellular ascorbate, the latter of which is subsequently
      regenerated by transplasma membrane ascorbate cycling.

PMID- 18347020
TI  - Structural insight into the mechanism of activation of the Toll receptor by the
      dimeric ligand Spatzle.
AB  - The Drosophila Toll receptor, which functions in both embryonic patterning and
      innate immunity to fungi and Gram-positive bacteria, is activated by a dimeric
      cytokine ligand, Spatzle (Spz). Previous studies have suggested that one Spz
      cross-links two Toll receptor molecules to form an activated complex. Here we
      report electron microscopy structures of the Toll ectodomain in the absence and
      presence of Spz. Contrary to expectations, Spz does not directly cross-link two
      Toll ectodomains. Instead, Spz binding at the N-terminal end of Toll
      predominantly induces the formation of a 2:2 complex, with two sites of
      interaction between the ectodomain chains, one located near to the N terminus of
      the solenoid and the other between the C-terminal juxtamembrane sequences.
      Moreover, Toll undergoes a ligand-induced conformational change, becoming more
      tightly curved than in the apo form. The unexpected 2:2 complex was confirmed by
      mass spectrometry under native conditions. These results suggest that activation
      of Toll is an allosteric mechanism induced by an end-on binding mode of its
      ligand Spz.

PMID- 18347021
TI  - Regulation of telomeric repeat binding factor 1 binding to telomeres by casein
      kinase 2-mediated phosphorylation.
AB  - Telomere maintenance is essential for continued cell proliferation and chromosome
      stability. Telomeres are maintained by telomerase and a collection of associated
      proteins. The telomeric protein telomeric repeat binding factor 1 (TRF1)
      negatively regulates telomere length by inhibiting access of telomerase at
      telomere termini. Here we report that TRF1 interacts with the beta subunit of
      casein kinase 2 (CK2) and serves as a substrate for CK2. CK2-mediated
      phosphorylation is required for the efficient telomere binding of TRF1 in vitro
      and in vivo. Inhibition of CK2 by the CK2 inhibitor 5,6-dichloro-1-beta-d
      ribofuranosylbenzimidazole decreased the ability of TRF1 to bind telomeric DNA.
      The resulting telomere-unbound form of TRF1 was then ubiquitinated and degraded
      by the proteasome. Partial knockdown of CK2 by small interfering RNA resulted in
      removal of TRF1 from telomeres and subsequent degradation of TRF1. Mapping of the
      CK2 target site identified threonine 122 as a substrate in TRF1. A threonine to
      alanine change at this position led to a diminished DNA binding due to reduced
      dimerization of TRF1. In addition, phosphorylation of threonine 122 seemed
      critical for TRF1-mediated telomere length control. Our findings suggest that CK2
      mediated phosphorylation of TRF1 plays an important role in modulating telomere
      length homeostasis by determining the levels of TRF1 at telomeres.

PMID- 18347022
TI  - Characterization of an orphan G protein-coupled receptor, GPR20, that
      constitutively activates Gi proteins.
AB  - GPR20 was isolated as an orphan G protein-coupled receptor from genomic DNA by
      PCR amplification. Although GPR20 was closely related to nucleotide or lipid
      receptors, the functional role of this receptor, as well as its endogenous
      ligand, remains unclear. Here we demonstrate that GPR20 is constitutively active
      in the absence of ligand, leading to continuous activation of its coupled G
      proteins. When GPR20 was exogenously expressed in HEK293 cells, both the basal
      level and the prostaglandin E(2)-induced production of cAMP were significantly
      decreased. A remarkable increase in [(35)S]guanosine 5'-(gamma-thio)triphosphate
      (GTPgammaS) binding to membrane preparations was also observed in GPR20
      expressing cells. These effects of GPR20 overexpression were diminished in cells
      treated with pertussis toxin, suggesting that the expression of GPR20 results in
      the activation of G(i/o) proteins. Involvement of GPR20 in the activation of
      G(i/o) proteins was also supported by evidence that the disruption of a conserved
      DRY motif in GPR20 attenuated both [(35)S]GTPgammaS incorporation and inhibition
      of the prostaglandin E(2)-induced cAMP production. Knockdown of GPR20 in PC12h
      cells resulted in an elevation of the basal cAMP level, suggesting that the
      endogenous GPR20 achieves a constitutively or spontaneously active conformation.
      Furthermore, enhancement of [(3)H]thymidine incorporation was also observed in
      the GPR20-silencing cells, implying that the GPR20 expression seems to attenuate
      PC12h cell growth. Taken together, these data indicate that GPR20 constitutively
      activates G(i) proteins without ligand stimulation. The receptor may be involved
      in cellular processes, including control of intracellular cAMP levels and
      mitogenic signaling.

PMID- 18347023
TI  - Cryptococcal xylosyltransferase 1 (Cxt1p) from Cryptococcus neoformans plays a
      direct role in the synthesis of capsule polysaccharides.
AB  - The opportunistic yeast Cryptococcus neoformans causes serious disease in humans
      and expresses a prominent polysaccharide capsule that is required for its
      virulence. Little is known about how this capsule is synthesized. We previously
      identified a beta1,2-xylosyltransferase (Cxt1p) with in vitro enzymatic activity
      appropriate for involvement in capsule synthesis. Here, we investigate C.
      neoformans strains in which the corresponding gene has been deleted (cxt1Delta).
      Loss of CXT1 does not affect in vitro growth of the mutant cells or the general
      morphology of their capsules. However, NMR structural analysis of the two main
      capsule polysaccharides, glucuronoxylomannan (GXM) and galactoxylomannan (GalXM),
      showed that both were missing beta1,2-xylose residues. There was an approximately
      30% reduction in the abundance of this residue in GXM in mutant compared with
      wild-type strains, and mutant GalXM was almost completely devoid of beta1,2
      linked xylose. The GalXM from the mutant strain was also missing a beta1,3-linked
      xylose residue. Furthermore, deletion of CXT1 led to attenuation of cryptococcal
      growth in a mouse model of infection, suggesting that the affected xylose
      residues are important for normal host-pathogen interactions. Cxt1p is the first
      glycosyltransferase with a defined role in C. neoformans capsule biosynthesis,
      and cxt1Delta is the only strain identified to date with structural alterations
      of the capsule polysaccharide GalXM.

PMID- 18347025
TI  - Endothelial cell migration in stable gradients of vascular endothelial growth
      factor A and fibroblast growth factor 2: effects on chemotaxis and chemokinesis.
AB  - Gradients of secreted signaling proteins guide growing blood vessels during both
      normal and pathological angiogenesis. However, the mechanisms by which
      endothelial cells integrate and respond to graded distributions of chemotactic
      factors are still poorly understood. We have in this study investigated
      endothelial cell migration in response to hill-shaped gradients of vascular
      endothelial growth factor A (VEGFA) and fibroblast growth factor 2 (FGF2) using a
      novel microfluidic chemotaxis chamber (MCC). Cell migration was scored at the
      level of individual cells using time-lapse microscopy. A stable gradient of
      VEGFA165 ranging from 0 to 50 ng/ml over a distance of 400 microm was shown to
      strongly induce chemotaxis of endothelial cells of different vascular origin.
      VEGFA121, unable to bind proteoglycan and neuropilin coreceptors, was also shown
      to induce chemotaxis in this setup. Furthermore, a gradient of FGF2 was able to
      attract venular but not arterial endothelial cells, albeit less efficiently than
      VEGFA165. Notably, constant levels of VEGFA165, but not of FGF2, were shown to
      efficiently reduce chemokinesis. Systematic exploration of different gradient
      shapes led to the identification of a minimal gradient steepness required for
      efficient cell guidance. Finally, analysis of cell migration in different regions
      of the applied gradients showed that chemotaxis is reduced when cells reach the
      high end of the gradient. Our findings suggest that chemotactic growth factor
      gradients may instruct endothelial cells to shift toward a nonmigratory phenotype
      when approaching the growth factor source.

PMID- 18347024
TI  - p21-activated kinase-aberrant activation and translocation in Alzheimer disease
      pathogenesis.
AB  - Defects in dendritic spines and synapses contribute to cognitive deficits in
      mental retardation syndromes and, potentially, Alzheimer disease. p21-activated
      kinases (PAKs) regulate actin filaments and morphogenesis of dendritic spines
      regulated by the Rho family GTPases Rac and Cdc42. We previously reported that
      active PAK was markedly reduced in Alzheimer disease cytosol, accompanied by
      downstream loss of the spine actin-regulatory protein Drebrin. beta-Amyloid
      (Abeta) oligomer was implicated in PAK defects. Here we demonstrate that PAK is
      aberrantly activated and translocated from cytosol to membrane in Alzheimer
      disease brain and in 22-month-old Tg2576 transgenic mice with Alzheimer disease.
      This active PAK coimmunoprecipitated with the small GTPase Rac and both
      translocated to granules. Abeta42 oligomer treatment of cultured hippocampal
      neurons induced similar effects, accompanied by reduction of dendrites that were
      protected by kinase-active but not kinase-dead PAK. Abeta42 oligomer treatment
      also significantly reduced N-methyl-d-aspartic acid receptor subunit NR2B
      phosphotyrosine labeling. The Src family tyrosine kinase inhibitor PP2
      significantly blocked the PAK/Rac translocation but not the loss of p-NR2B in
      Abeta42 oligomer-treated neurons. Src family kinases are known to phosphorylate
      the Rac activator Tiam1, which has recently been shown to be Abeta-responsive. In
      addition, anti-oligomer curcumin comparatively suppressed PAK translocation in
      aged Tg2576 transgenic mice with Alzheimer amyloid pathology and in Abeta42
      oligomer-treated cultured hippocampal neurons. Our results implicate aberrant PAK
      in Abeta oligomer-induced signaling and synaptic deficits in Alzheimer disease.

PMID- 18347026
TI  - Day-case diagnostic and interventional peripheral angiography: 10-year experience
      in a radiology specialist nurse-led unit.
AB  - We describe a prospective evaluation of the safety of peripheral angiography
      procedures performed on day-case patients in a dedicated radiological nurse-led
      and administrated unit. Patients referred for peripheral vascular angiography,
      over a 10-year period, were pre-assessed by a radiology specialist nurse in a
      nurse-led clinic. Radiologists performed all procedures, whereas radiology
      specialist nurses were responsible for patient care before, during and after
      angiography and during the 24 h follow-up. Procedures were divided into
      diagnostic or interventional; complications were divided into immediate or
      delayed (24 h follow-up) either requiring hospital admission (major) or day-case
      unit management (minor). Patient acceptability was assessed using a standard
      questionnaire. Cost analysis was also performed. 401 day-case peripheral
      angiography procedures (144 diagnostic and 257 interventional) were performed in
      310 patients. 109/401 (27.2%) procedures were performed on patients with diabetes
      mellitus. In diagnostic studies, 16/144 (11.1%) immediate and 6/144 (4.2%)
      delayed complications occurred whereas, in interventional studies, 65/257 (25.3%)
      immediate and 13/257 (5.1%) delayed complications were noted. A major
      complication occurred in 17/257 (6.6%) of patients in the interventional group
      and 3/144 (2.1%) in the diagnostic group. Puncture site haematoma was the most
      common complication. Nurse-led care was acceptable to the patient, with a high
      level of patient satisfaction seen. In conclusion, day-case diagnostic and
      interventional peripheral angiography procedures can be performed safely in a
      specialist nurse-led and administrated unit, with complication rates being within
      the accepted guidelines.

PMID- 18347027
TI  - Left ventricular ejection fraction using 64-slice CT coronary angiography and new
      evaluation software: initial experience.
AB  - The purpose of this study was to evaluate the feasibility and reliability of
      software-based quantification of left ventricular function using 64-slice CT
      coronary angiography. Data were collected from 26 subjects who underwent a 64
      slice coronary CT angiography study. Two volumetric data sets at end diastole and
      end systole were reconstructed from each scan by means of retrospective
      electrocardiogram gating. Data sets were evaluated with a prototype of now
      commercially available software (Syngo Circulation I; Siemens Medical Solutions,
      Erlangen, Germany), which automatically segments the blood volume in the left
      ventricle after the user defines the mitral valve plane and any point within the
      ventricle. After segmentation of the blood pool in end systole and end diastole,
      the software automatically measures end systolic and end diastolic volume and
      calculates stroke volume and ejection fraction (EF). Two readers processed all CT
      data sets twice to assess for intra- and inter-observer variation. In addition,
      CT EF measurements were compared with those obtained by clinical
      echocardiography. Intra-observer variation for the calculated EF with CT were
      13.6% and 15.6% for Readers 1 and 2, respectively. No significant difference in
      left ventricular functional parameters on CT existed between the readers (p >
      0.05). A Bland-Altman plot revealed a slight mean difference between EF
      measurements on CT and echocardiography, with all differences falling within two
      standard deviations of the mean in the setting of wide limits of agreement. In
      conclusion, assessment of left ventricular EF from CT coronary data using the new
      analysis software is rapid and easy. The software is user-friendly and provides
      good reproducibility for EF measurements with CT.

PMID- 18347028
TI  - Pre-operative MR assessment of recurrent rectal cancer.
AB  - The potential for curative resection of recurrent rectal cancer and the
      recognized benefits of palliative resection have led to increased numbers of
      patients being referred for MRI assessment. This study assesses the use of MRI to
      provide a roadmap of tumour recurrence to allow for appropriate surgical
      planning. Differentiation of recurrent rectal cancer from post-surgical and post
      radiotherapy changes on MR proved particularly problematic when assessing the
      pelvic sidewalls. Areas of uncertainty on imaging, therefore, need to be
      discussed on a case by case basis regarding the decision to proceed to curative
      or explorative surgery.

PMID- 18347029
TI  - Tailored CT: primum non nocere.
AB  - Despite its vital diagnostic utility, the ionizing radiation used in CT is not
      benign. Patients have an increased risk of dying from a radiation-induced cancer
      for every pass through a CT scanner. One way to reduce this risk is to tailor CT,
      especially follow-up scans, to specific areas of concern. By doing so, we can
      help to minimize the small but real risk from this essential technology.

PMID- 18347030
TI  - The use of a commercial remote desktop program in the delineation of target
      volumes in radiotherapy.
AB  - Recent guidance from the Royal College of Radiologists suggests that there should
      be close collaboration between oncologists and radiologists in target volume
      determination. However, the guidance also states that there may be practical
      difficulties in achieving this. To ameliorate some of these difficulties, we have
      implemented a readily available remote desktop package, Microsoft NetMeeting, in
      conjunction with a commercial virtual simulation package, ProSoma. This allows
      radiologists to conference easily with oncologists on a particular patient, as
      the full functionality of the virtual simulator is available simultaneously to
      both parties. We have found that this solution is eminently practical and
      increases the amount of interaction between oncologists and radiologists during
      target volume definition.

PMID- 18347031
TI  - Burkholderia pseudomallei infection of T cells leads to T-cell costimulation
      partially provided by flagellin.
AB  - Burkholderia pseudomallei is the causative agent of melioidosis. While adaptive
      immunity has been shown to be important for host resistance to B. pseudomallei,
      the direct interaction of the bacteria with adaptive immune cells such as T and B
      cells is not well known. To address this question, we infected Jurkat T cells, as
      well as human primary CD4(+) and CD8(+) T cells, with live B. pseudomallei. We
      found that live bacterial infection could costimulate T cells to produce
      interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in the presence of anti-CD3
      cross-linking antibodies. Bacterial supernatant could also costimulate T cells,
      and this was due to the presence of flagellin in the supernatant. However, T
      cells infected with bacterial mutants lacking flagellin showed strong impairment
      in IL-2 but only a slight impairment in IFN-gamma production. When cross-linking
      of CD3 is replaced by IL-2, live bacterial infection was still able to
      costimulate human primary T cells to produce IFN-gamma and flagellin is only a
      minor ligand contributing to this costimulation. Thus, live B. pseudomallei could
      potentially costimulate T cells not only in an antigen-specific manner but also
      in a nonspecific manner through bystander activation via IL-2.

PMID- 18347032
TI  - Both CD4+ and CD8+ T cells respond to antigens fused to anthrax lethal toxin.
AB  - The lethal toxin produced by Bacillus anthracis is a bipartite toxin in which the
      first protein, protective antigen (PA), transports the second protein, lethal
      factor, across the host cell membrane. We have previously shown that CD8(+) T
      cell epitopes fused to a nontoxic derivative of lethal factor (LFn) are delivered
      into the host cell cytosol in a PA-dependent manner. Delivery of these antigens
      targets them to the intracellular major histocompatibility complex (MHC) class I
      processing and presentation pathway and leads to the stimulation of antigen
      specific CD8(+) T cells in vivo. In this report, we describe the generation and
      characterization of LFn fusion proteins that include not only a CD8(+) T-cell
      epitope but also a CD4(+) T-cell epitope. We first show that these fusion
      proteins induce antigen-specific CD4(+) T-cell responses following incubation
      with dendritic cells in vitro or injection into mice. Stimulation of CD4(+) T
      cells by LFn fusion proteins does not require PA but is enhanced by PA in vitro.
      We also show that a single LFn fusion protein and PA can deliver antigen to both
      the MHC class II and the MHC class I pathways, resulting in the simultaneous
      induction of antigen-specific CD4(+) T cells and antigen-specific CD8(+) T cells
      in the same mouse. These results suggest that this toxin delivery system is
      capable of stimulating protective immune responses where effective immunization
      requires stimulation of both classes of T cells.

PMID- 18347033
TI  - EmaA, a potential virulence determinant of Aggregatibacter actinomycetemcomitans
      in infective endocarditis.
AB  - The gram-negative fastidious human oropharyngeal Aggregatibacter
      actinomycetemcomitans is implicated in the etiology of infective endocarditis.
      EmaA, an oligomeric coiled-coil adhesin homologous to YadA of Yersinia
      enterocolitica, was hypothesized to mediate the interaction of A.
      actinomycetemcomitans with collagen. Collagen, the most abundant protein in human
      bodies and the main component of extracellular matrix (ECM), predominates in the
      supporting tissue of cardiac valves. To extend our earlier studies using purified
      collagen to determine bacterial binding activities, we developed a tissue model
      using rabbit cardiac valves to investigate the interaction of A.
      actinomycetemcomitans with native collagen. The resected mitral valves, with or
      without removal of the endothelium, were incubated with equivalent numbers of the
      wild type and the isogenic emaA mutant defective in collagen binding. There was
      no difference in binding between the wild-type and the mutant strains when the
      endothelium remained intact. However, the emaA mutant was fivefold less effective
      than the wild-type strain in colonizing the exposed ECM. A 10-fold increase in
      the binding of the wild-type strain to ECM was observed compared with the intact
      endothelium. Similar observations were replicated in an in vivo endocarditis
      rabbit model; the emaA mutant was 10-fold less effective in the initial infection
      of the traumatized aortic valve. Colocalization studies indicated that A.
      actinomycetemcomitans bound to type I collagen. A. actinomycetemcomitans
      preferentially colonized the ECM and, together with the evidence that EmaA
      interacts with the native collagen, suggested that the adhesin is likely a
      potential virulence determinant of the bacterium in the initiation of infective
      endocarditis.

PMID- 18347034
TI  - Dominant role of paraoxonases in inactivation of the Pseudomonas aeruginosa
      quorum-sensing signal N-(3-oxododecanoyl)-L-homoserine lactone.
AB  - The pathogenic bacterium Pseudomonas aeruginosa causes serious infections in
      immunocompromised patients. N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL)
      is a key component of P. aeruginosa's quorum-sensing system and regulates the
      expression of many virulence factors. 3OC12-HSL was previously shown to be
      hydrolytically inactivated by the paraoxonase (PON) family of calcium-dependent
      esterases, consisting of PON1, PON2, and PON3. Here we determined the specific
      activities of purified human PONs for 3OC12-HSL hydrolysis, including the common
      PON1 polymorphic forms, and found they were in the following order: PON2 >>
      PON1(192R) > PON1(192Q) > PON3. PON2 exhibited a high specific activity of 7.6 +/
      0.4 micromols/min/mg at 10 microM 3OC12-HSL, making it the best PON2 substrate
      identified to date. By use of class-specific inhibitors, approximately 85 and 95%
      of the 3OC12-HSL lactonase activity were attributable to PON1 in mouse and human
      sera, respectively. In mouse liver homogenates, the activity was metal dependent,
      with magnesium- and manganese-dependent lactonase activities comprising 10 to 15%
      of the calcium-dependent activity. In mouse lung homogenates, all of the activity
      was calcium dependent. The calcium-dependent activities were irreversibly
      inhibited by extended EDTA treatment, implicating PONs as the major enzymes
      inactivating 3OC12-HSL. In human HepG2 and EA.hy 926 cell lysates, the 3OC12-HSL
      lactonase activity closely paralleled the PON2 protein levels after PON2
      knockdown by small interfering RNA treatment of the cells. These findings suggest
      that PONs, particularly PON2, could be an important mechanism by which 3OC12-HSL
      is inactivated in mammals.

PMID- 18347035
TI  - Heterogeneity in the polarity of Nra regulatory effects on streptococcal pilus
      gene transcription and virulence.
AB  - Transcription of several key virulence factors of Streptococcus pyogenes is under
      the control of Mga and Nra/RofA. In an M serotype 49 (M49) strain, Nra is a
      negative regulator of pilus gene transcription; also, Nra represses mga
      expression, leading to downregulation of the M protein surface fibril and
      secreted cysteine protease SpeB. In this report, the role of Nra in the virulence
      of an M53 classical skin strain was investigated. In contrast to the case for the
      M49 strain, Nra functions as a positive regulator of pilus gene transcription in
      the M53 strain, and inactivation of nra leads to loss of virulence in a humanized
      mouse model of superficial skin infection. Furthermore, Nra has no measurable
      effect on mga transcription in the M53 strain; this finding is further supported
      by a lack of detectable Nra effects on M protein- and SpeB-dependent phenotypes.
      Whereas MsmR is reported to activate nra and pilus gene transcription in the M49
      strain, in the M53 strain it acts as a repressor of these genes. In both strains,
      MsmR and Nra form a feed-forward loop network motif for pilus gene transcription,
      but their effects have opposite signs. The findings demonstrate key strain
      specific differences in the transcriptional circuitry governing virulence gene
      expression in S. pyogenes and its impact on pathogenesis.

PMID- 18347036
TI  - Role for nitric oxide in hookworm-associated immune suppression.
AB  - Hookworm infection is a major cause of anemia and malnutrition in resource-poor
      countries. Human and animal studies suggest that infection with these intestinal
      nematodes is associated with impaired cellular immunity, characterized by reduced
      lymphocyte proliferation in response to both parasite and heterologous antigens.
      We report here data from studies aimed at defining mechanisms through which
      hookworms modulate the host cellular immune response. Splenocytes and mesenteric
      lymph node (MLN) cells from hamsters infected with Ancylostoma ceylanicum showed
      minimal proliferation in response to mitogen at days 20 and 30 postinfection
      (p.i.), with partial recovery noted at day 70 p.i. The proliferative capacity of
      enriched splenocyte T-cell preparations from infected animals following
      stimulation with hookworm antigens was partially restored in the presence of
      antigen-presenting cells from uninfected hamsters. Analysis by fluorescence
      activated cell sorting revealed that hookworm infection is associated with
      reduced percentages of both CD4(+) and surface immunoglobulin G-positive
      lymphocytes in the spleen and MLN cells. Splenocytes from infected hamsters also
      secreted more nitric oxide (NO) in culture than did those from naive animals.
      Inhibition of NO secretion was associated with partial restoration of the
      proliferative capacity of splenocytes from infected animals in response to
      concanavalin A, suggesting a role for NO in mediating this effect. Together,
      these data demonstrate that hookworm infection is associated with impaired
      function of antigen-presenting cells and depletion of important lymphocyte
      subpopulations and also suggests a role for NO in parasite-induced
      immunosuppression.

PMID- 18347037
TI  - A cluster of four surface antigen genes specifically expressed in bradyzoites,
      SAG2CDXY, plays an important role in Toxoplasma gondii persistence.
AB  - Toxoplasma gondii is one of the most successful protozoan parasites of warm
      blooded animals. Stage-specific expression of its surface molecules is thought to
      be key to its ability to establish chronic infection in immunocompetent animals.
      The rapidly dividing tachyzoite stage displays a different subset of family of
      surface antigen 1 (SAG1)-related sequences (SRSs) from that displayed by the
      encysted bradyzoite stage. It is possible that this switch is necessary to
      protect the bradyzoites against an immune response raised against the tachyzoite
      stage. Alternatively, it might be that bradyzoite SRSs evolved to facilitate
      invasion of different cell types, such as those found in the brain, where cysts
      develop, or the small intestine, where bradyzoites must enter after oral
      infection. Here we studied the function of a cluster of four tandem genes,
      encoding bradyzoite SRSs called SAG2C, -D, -X, and -Y. Using bioluminescence
      imaging of mice infected with parasites expressing firefly luciferase (FLUC)
      driven by the SAG2D promoter, we show stage conversion for the first time in
      living animals. A truncated version of the SAG2D promoter (SAG2Dmin) gave
      efficient expression of FLUC in both tachyzoites and bradyzoites, indicating that
      the bradyzoite specificity of the complete SAG2D promoter is likely due to an
      element(s) that normally suppresses expression in tachyzoites. Comparing mice
      infected with the wild type or a mutant where the SAG2CDXY cluster of genes has
      been deleted (DeltaSAG2CDXY), we demonstrate that whereas DeltaSAG2CDXY parasites
      are less capable of maintaining a chronic infection in the brain, they do not
      show a defect in oral infectivity.

PMID- 18347038
TI  - Glycogen and maltose utilization by Escherichia coli O157:H7 in the mouse
      intestine.
AB  - Mutant screens and transcriptome studies led us to consider whether the
      metabolism of glucose polymers, i.e., maltose, maltodextrin, and glycogen, is
      important for Escherichia coli colonization of the intestine. By using the
      streptomycin-treated mouse model, we found that catabolism of the disaccharide
      maltose provides a competitive advantage in vivo to pathogenic E. coli O157:H7
      and commensal E. coli K-12, whereas degradation of exogenous forms of the more
      complex glucose polymer, maltodextrin, does not. The endogenous glucose polymer,
      glycogen, appears to play an important role in colonization, since mutants that
      are unable to synthesize or degrade glycogen have significant colonization
      defects. In support of the hypothesis that E. coli relies on internal carbon
      stores to maintain colonization during periods of famine, we found that by
      providing a constant supply of a readily metabolized sugar, i.e., gluconate, in
      the animal's drinking water, the competitive disadvantage of E. coli glycogen
      metabolism mutants is rescued. The results suggest that glycogen storage may be
      widespread in enteric bacteria because it is necessary for maintaining rapid
      growth in the intestine, where there is intense competition for resources and
      occasional famine. An important implication of this study is that the sugars used
      by E. coli are present in limited quantities in the intestine, making endogenous
      carbon stores valuable. Thus, there may be merit to combating enteric infections
      by using probiotics or prebiotics to manipulate the intestinal microbiota in such
      a way as to limit the availability of sugars preferred by E. coli O157:H7 and
      perhaps other pathogens.

PMID- 18347039
TI  - Genetic evidence for an alternative citrate-dependent biofilm formation pathway
      in Staphylococcus aureus that is dependent on fibronectin binding proteins and
      the GraRS two-component regulatory system.
AB  - We reported previously that low concentrations of sodium citrate strongly promote
      biofilm formation by Staphylococcus aureus laboratory strains and clinical
      isolates. Here, we show that citrate promotes biofilm formation via stimulating
      both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm
      formation is independent of the ica locus, and in fact, citrate represses
      polysaccharide adhesin production. We show that fibronectin binding proteins FnbA
      and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB
      gene expression, are required for citrate's positive effects on biofilm
      formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm
      formation is also stimulated by several other tricarboxylic acid (TCA) cycle
      intermediates in an FnbA-dependent fashion. While aconitase contributes to
      biofilm formation in the absence of TCA cycle intermediates, it is not required
      for biofilm stimulation by these compounds. Furthermore, the GraRS two-component
      regulator and the GraRS-regulated efflux pump VraFG, identified for their roles
      in intermediate vancomycin resistance, are required for citrate-stimulated cell
      to-cell interactions, but the GraRS regulatory system does not impact the
      expression of the fnbA and fnbB genes. Our data suggest that distinct genetic
      factors are required for the early steps in citrate-stimulated biofilm formation.
      Given the role of FnbA/FnbB and SarA in virulence in vivo and the lack of a role
      for ica-mediated biofilm formation in S. aureus catheter models of infection, we
      propose that the citrate-stimulated biofilm formation pathway may represent a
      clinically relevant pathway for the formation of these bacterial communities on
      medical implants.

PMID- 18347040
TI  - Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman
      primates.
AB  - Understanding the physical characteristics of the local microenvironment in which
      Mycobacterium tuberculosis resides is an important goal that may allow the
      targeting of metabolic processes to shorten drug regimens. Pimonidazole
      hydrochloride (Hypoxyprobe) is an imaging agent that is bioreductively activated
      only under hypoxic conditions in mammalian tissue. We employed this probe to
      evaluate the oxygen tension in tuberculous granulomas in four animal models of
      disease: mouse, guinea pig, rabbit, and nonhuman primate. Following infusion of
      pimonidazole into animals with established infections, lung tissues from the
      guinea pig, rabbit, and nonhuman primate showed discrete areas of pimonidazole
      adduct formation surrounding necrotic and caseous regions of pulmonary granulomas
      by immunohistochemical staining. This labeling could be substantially reduced by
      housing the animal under an atmosphere of 95% O(2). Direct measurement of tissue
      oxygen partial pressure by surgical insertion of a fiber optic oxygen probe into
      granulomas in the lungs of living infected rabbits demonstrated that even small
      (3-mm) pulmonary lesions were severely hypoxic (1.6 +/- 0.7 mm Hg). Finally,
      metronidazole, which has potent bactericidal activity in vitro only under low
      oxygen culture conditions, was highly effective at reducing total-lung bacterial
      burdens in infected rabbits. Thus, three independent lines of evidence support
      the hypothesis that hypoxic microenvironments are an important feature of some
      lesions in these animal models of tuberculosis.

PMID- 18347041
TI  - Entamoeba histolytica encodes unique formins, a subset of which regulates DNA
      content and cell division.
AB  - The formin family of proteins mediates dynamic changes in actin assembly in
      eukaryotes, and therefore it is important to understand the function of these
      proteins in Entamoeba histolytica, where actin forms the major cytoskeletal
      network. In this study we have identified the formin homologs encoded in the E.
      histolytica genome based on sequence analysis. Using multiple tools, we have
      analyzed the primary sequences of the eight E. histolytica formins and discovered
      three subsets: (i) E. histolytica formin-1 to -3 (Ehformin-1 to -3), (ii)
      Ehformin-4, and (iii) Ehformin-5 to -8. Two of these subsets (Ehformin-1 to -3
      and Ehformin-4) showed significant sequence differences from their closest
      homologs, while Ehformin-5 to -8 were unique among all known formins. Since
      Ehformin-1 to -3 showed important sequence differences from Diaphanous-related
      formins (DRFs), we have studied the functions of Ehformin-1 and -2 in E.
      histolytica transformants. Like other DRFs, Ehformin-1 and -2 associated with F
      actin in response to serum factors, in pseudopodia, in pinocytic and phagocytic
      vesicles, and at cell division sites. Ehformin-1 and -2 also localized with the
      microtubular assembly in the nucleus, indicating their involvement in genome
      segregation. While increased expression of Ehformin-1 and -2 did not affect
      phagocytosis or motility, it clearly showed an increase in the number of
      binucleated cells, the number of nuclei in multinucleated cells, and the average
      DNA content of each nucleus, suggesting that these proteins regulate both mitosis
      and cytokinesis in E. histolytica.

PMID- 18347042
TI  - Trypanosoma cruzi induces regulatory dendritic cells in vitro.
AB  - A main feature of acute infection with Trypanosoma cruzi is the presence of
      immunological disorders. A previous study demonstrated that acute infection with
      the virulent RA strain downregulates the expression of major histocompatibility
      complex class II (MHC-II) on antigen-presenting cells and impairs the T-cell
      stimulatory capacity of splenic dendritic cells (DC). In the present work, we
      assessed the ability of trypomastigotes (Tp) to modulate the differentiation
      stage and functionality of bone marrow-derived DC in vitro. We observed that the
      Tp stage of T. cruzi failed to activate DC, which preserved their low expression
      of MHC-II and costimulatory molecules, as well as their endocytic activity. We
      also show that Tp induced transforming growth factor beta (TGF-beta) secretion by
      DC and enhanced the gap between interleukin-10 (IL-10) and IL-12p70 production,
      showing a higher IL-10/IL-12p70 ratio upon lipopolysaccharide (LPS) treatment. In
      addition, we observed that Tp prevented DC full activation induced by LPS,
      thereby downregulating their MHC-II surface expression and inhibiting their
      capacity to stimulate lymphocyte proliferation. In vitro IL-10 neutralization
      during the differentiation process of DC with Tp+LPS showed a reversion of their
      inhibitory effect during mixed lymphocyte reaction. In contrast, only
      simultaneous neutralization of IL-10 and TGF-beta, after DC differentiation, was
      involved in the partial restitution of lymphocyte proliferation. Since both TGF
      beta and IL-10 are immunosuppressive cytokines essential in the modulation of the
      immune response and important in the induction of tolerance, our results suggest
      for the first time that Tp are responsible for the generation of regulatory DC in
      vitro.

PMID- 18347043
TI  - On rejection.

PMID- 18347044
TI  - Lipooligosaccharides containing phosphorylcholine delay pulmonary clearance of
      nontypeable Haemophilus influenzae.
AB  - Nontypeable Haemophilus influenzae (NTHi) causes pulmonary infections in patients
      with chronic obstructive pulmonary disease and other mucociliary clearance
      defects. Like many bacteria inhabiting mucosal surfaces, NTHi produces
      lipooligosaccharide (LOS) endotoxins that lack the O side chain. Persistent NTHi
      populations express a discrete subset of LOS glycoforms, including those
      containing phosphorylcholine (PCho). In this study, we compared two NTHi strains
      with isogenic mutants lacking PCho for clearance from mice following pulmonary
      infection. Consistent with data from other model systems, populations of the
      strains NTHi 2019 and NTHi 86-028NP recovered from mouse lung contained an
      increased proportion of PCho+ variants compared to that in the inocula. PCho-
      mutants were more rapidly cleared. Serial passage of NTHi increased both PCho
      content and bacterial resistance to clearance, and no such increases were
      observed for PCho- mutants. Increased PCho content was also observed in NTHi
      populations within non-endotoxin-responsive C3H/HeJ and Toll-like receptor 4 null
      (TLR4-/-) mice, albeit at later times postinfection. Changes in bacterial
      subpopulations and clearance were unaffected in TLR2-/- mice compared to the
      subpopulations in and clearance from mice of the parental strain. The clearance
      of PCho- mutants occurred at earlier time points in both strain backgrounds and
      in all types of mice. Comparison of bacterial populations in lung tissue
      cryosections by immunofluorescent staining showed sparse bacteria within the air
      spaces of C57BL/6 mice and large bacterial aggregates within the lungs of MyD88-/
      mice. These results indicate that PCho promotes bacterial resistance to
      pulmonary clearance early in infection in a manner that is at least partially
      independent of the TLR4 pathway.

PMID- 18347045
TI  - The Chlamydia trachomatis plasmid is a transcriptional regulator of chromosomal
      genes and a virulence factor.
AB  - Chlamydia trachomatis possesses a cryptic 7.5-kb plasmid of unknown function.
      Here, we describe a comprehensive molecular and biological characterization of
      the naturally occurring plasmidless human C. trachomatis strain L2(25667R). We
      found that despite minimal chromosomal polymorphisms, the LGV strain L2(25667R)
      was indistinguishable from plasmid-positive strain L2(434) with regard to its in
      vitro infectivity characteristics such as growth kinetics, plaquing efficiency,
      and plaque size. The only in vitro phenotypic differences between L2(434) and
      L2(25667R) were the accumulation of glycogen granules in the inclusion matrix and
      the lack of the typical intrainclusion Brownian-like movement characteristic of
      C. trachomatis strains. Conversely, we observed a marked difference between the
      two strains in their abilities to colonize and infect the female mouse genital
      tract. The 50% infective dose of plasmidless strain L2(25667R) was 400-fold
      greater (4 x 10(6) inclusion-forming units [IFU]) than that of plasmid-bearing
      strain L2(434) (1 x 10(4) IFU). Transcriptome analysis of the two strains
      demonstrated a decrease in the transcript levels of a subset of chromosomal genes
      for strain L2(25667R). Among those genes was glgA, encoding glycogen synthase, a
      finding consistent with the failure of L2(25667R) to accumulate glycogen
      granules. These findings support a primary role for the plasmid in in vivo
      infectivity and suggest that virulence is controlled, at least in part, by the
      plasmid's ability to regulate the expression of chromosomal genes. Our findings
      have important implications in understanding a role for the plasmid in the
      pathogenesis of human infection and disease.

PMID- 18347046
TI  - Identification of TbpA residues required for transferrin-iron utilization by
      Neisseria gonorrhoeae.
AB  - Neisseria gonorrhoeae requires iron for survival in the human host and therefore
      expresses high-affinity receptors for iron acquisition from host iron-binding
      proteins. The gonococcal transferrin-iron uptake system is composed of two
      transferrin binding proteins, TbpA and TbpB. TbpA is a TonB-dependent, outer
      membrane transporter critical for iron acquisition, while TbpB is a surface
      exposed lipoprotein that increases the efficiency of iron uptake. The precise
      mechanism by which TbpA mediates iron acquisition has not been elucidated;
      however, the process is distinct from those of characterized siderophore
      transporters. Similar to these TonB-dependent transporters, TbpA is proposed to
      have two distinct domains, a beta-barrel and a plug domain. We hypothesize that
      the TbpA plug coordinates iron and therefore potentially functions in multiple
      steps of transferrin-mediated iron acquisition. To test this hypothesis, we
      targeted a conserved motif within the TbpA plug domain and generated single,
      double, and triple alanine substitution mutants. Mutagenized TbpAs were expressed
      on the gonococcal cell surface and maintained wild-type transferrin binding
      affinity. Single alanine substitution mutants internalized iron at wild-type
      levels, while the double and triple mutants showed a significant decrease in iron
      uptake. Moreover, the triple alanine substitution mutant was unable to grow on
      transferrin as a sole iron source; however, expression of TbpB compensated for
      this defect. These data indicate that the conserved motif between residues 120
      and 122 of the TbpA plug domain is critical for transferrin-iron utilization,
      suggesting that this region plays a role in iron acquisition that is shared by
      both TbpA and TbpB.

PMID- 18347047
TI  - Staphylococcus aureus CcpA affects biofilm formation.
AB  - Biofilm formation in Staphylococcus aureus under in vitro growth conditions is
      generally promoted by high concentrations of sugar and/or salts. The addition of
      glucose to routinely used complex growth media triggered biofilm formation in S.
      aureus strain SA113. Deletion of ccpA, coding for the catabolite control protein
      A (CcpA), which regulates gene expression in response to the carbon source,
      abolished the capacity of SA113 to form a biofilm under static and flow
      conditions, while still allowing primary attachment to polystyrene surfaces. This
      suggested that CcpA mainly affects biofilm accumulation and intercellular
      aggregation. trans-Complementation of the mutant with the wild-type ccpA allele
      fully restored the biofilm formation. The biofilm produced by SA113 was
      susceptible to sodium metaperiodate, DNase I, and proteinase K treatment,
      indicating the presence of polysaccharide intercellular adhesin (PIA), protein
      factors, and extracellular DNA (eDNA). The investigation of several factors which
      were reported to influence biofilm formation in S. aureus (arlRS, mgrA, rbf,
      sarA, atl, ica, citZ, citB, and cidABC) showed that CcpA up-regulated the
      transcription of cidA, which was recently shown to contribute to eDNA production.
      Moreover, we showed that CcpA increased icaA expression and PIA production,
      presumably over the down-regulation of the tricarboxylic acid cycle genes citB
      and citZ.

PMID- 18347048
TI  - T cells help to amplify inflammatory responses induced by Salmonella enterica
      serotype Typhimurium in the intestinal mucosa.
AB  - Salmonella enterica serotype Typhimurium causes an acute inflammatory reaction in
      the ceca of streptomycin-pretreated mice. We determined global changes in gene
      expression elicited by serotype Typhimurium in the cecal mucosa. The gene
      expression profile was dominated by T-cell-derived cytokines and genes whose
      expression is known to be induced by these cytokines. Markedly increased mRNA
      levels of genes encoding gamma interferon (IFN-gamma), interleukin-22 (IL-22),
      and IL-17 were detected by quantitative real-time PCR. Furthermore, the mRNA
      levels of genes whose expression is induced by IFN-gamma, IL-22, or IL-17,
      including genes encoding macrophage inflammatory protein 2 (MIP-2), inducible
      nitric oxide synthase (Nos2), lipocalin-2 (Lcn2), MIP-1alpha, MIP-1beta, and
      keratinocyte-derived cytokine (KC), were also markedly increased. To assess the
      importance of T cells in orchestrating this proinflammatory gene expression
      profile, we depleted T cells by using a monoclonal antibody prior to
      investigating cecal inflammation caused by serotype Typhimurium in streptomycin
      pretreated mice. Depletion of CD3+ T cells resulted in a dramatic reduction in
      gross pathology, a significantly reduced recruitment of neutrophils, and a marked
      reduction in mRNA levels of Ifn-gamma, Il-22, Il-17, Nos2, Lcn2, and Kc. Our
      results suggest that T cells play an important role in amplifying inflammatory
      responses induced by serotype Typhimurium in the cecal mucosa.

PMID- 18347049
TI  - Wall teichoic acid deficiency in Staphylococcus aureus confers selective
      resistance to mammalian group IIA phospholipase A(2) and human beta-defensin 3.
AB  - Wall teichoic acids (WTAs) and membrane lipoteichoic acids (LTAs) are the major
      polyanionic polymers in the envelope of Staphylococcus aureus. WTAs in S. aureus
      play an important role in bacteriophage attachment and bacterial adherence to
      certain host cells, suggesting that WTAs are exposed on the cell surface and
      could also provide necessary binding sites for cationic antimicrobial peptides
      and proteins (CAMPs). Highly cationic mammalian group IIA phospholipase A(2)
      (gIIA PLA(2)) kills S. aureus at nanomolar concentrations by an action(s) that
      depends on initial electrostatic interactions, cell wall penetration, membrane
      phospholipid (PL) degradation, and activation of autolysins. A tagO mutant of S.
      aureus that lacks WTA is up to 100-fold more resistant to PL degradation and
      killing by gIIA PLA(2) and CAMP human beta-defensin 3 (HBD-3) but has the
      sensitivity of the wild type (wt) to other CAMPs, such as Magainin II amide, hNP1
      3, LL-37, and lactoferrin. In contrast, there is little or no difference in
      either gIIA PLA(2) activity toward cell wall-depleted protoplasts of the wt and
      tagO strains of S. aureus or in binding of gIIA PLA(2) to wt and tagO strains.
      Scanning and transmission electron microscopy reveal increased surface
      protrusions in the S. aureus tagO mutant that might account for reduced activity
      of bound gIIA PLA(2) and HBD-3 toward the tagO mutant. In summary, the absence of
      WTA in S. aureus causes a selective increase in bacterial resistance to gIIA
      PLA(2) and HBD-3, the former apparently by reducing access and/or activity of
      bound antibacterial enzyme to the bacterial membrane.

PMID- 18347050
TI  - Vibrio parahaemolyticus inhibition of Rho family GTPase activation requires a
      functional chromosome I type III secretion system.
AB  - Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis;
      however, its virulence mechanisms are not well understood. The identification of
      type III secreted proteins has provided candidate virulence factors whose
      functions are still being elucidated. Genotypic strain variability contributes a
      level of complexity to understanding the role of different virulence factors. The
      ability of V. parahaemolyticus to inhibit Rho family GTPases and cause
      cytoskeletal disruption was examined with HeLa cells. After HeLa cells were
      infected, intracellular Rho activation was inhibited in response to external
      stimuli. In vitro activation of Rho, Rac, and Cdc42 isolated from infected HeLa
      cell lysates was also inhibited, indicating that the bacteria were specifically
      targeting GTPase activation. The inhibition of Rho family GTPase activation was
      retained for clinical and environmental isolates of V. parahaemolyticus and was
      dependent on a functional chromosome I type III secretion system (CI-T3SS).
      GTPase inhibition was independent of hemolytic toxin genotype and the chromasome
      II (CII)-T3SS. Rho inhibition was accompanied by a shift in the total actin pool
      to its monomeric form. These phenotypes were abrogated in a mutant strain lacking
      the CI-T3S effector Vp1686, suggesting that the inhibiting actin polymerization
      may be a downstream effect of Vp1686-dependent GTPase inhibition. Although Vp1686
      has been previously characterized as a potential virulence factor in macrophages,
      our findings reveal an effect on cultured HeLa cells. The ability to inhibit Rho
      family GTPases independently of the CII-T3SS and the hemolytic toxins may provide
      insight into the mechanisms of virulence used by strains lacking these virulence
      factors.

PMID- 18347051
TI  - Yersinia pestis caf1 variants and the limits of plague vaccine protection.
AB  - Yersinia pestis, the highly virulent agent of plague, is a biological weapon.
      Strategies that prevent plague have been sought for centuries, and immunization
      with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1)
      antigen is considered effective. We show here that immunization with live,
      attenuated strains generates plague-protective immunity and humoral immune
      responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1
      pili) are not only fully virulent in animal models of bubonic and pneumonic
      plague but also break through immune responses generated with live, attenuated
      strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a
      protein at the tip of type III needles, generates protective immunity against the
      wild-type and the fully virulent caf1 mutant strain, in agreement with the notion
      that LcrV can elicit vaccine protection against both types of virulent plague
      strains.

PMID- 18347052
TI  - The U11-48K protein contacts the 5' splice site of U12-type introns and the U11
      59K protein.
AB  - Little is currently known about proteins that make contact with the pre-mRNA in
      the U12-dependent spliceosome and thereby contribute to intron recognition. Using
      site-specific cross-linking, we detected an interaction between the U11-48K
      protein and U12-type 5' splice sites (5'ss). This interaction did not require
      branch point recognition and was sensitive to 5'ss mutations, suggesting that 48K
      interacts with the 5'ss during the first steps of prespliceosome assembly in a
      sequence-dependent manner. RNA interference-induced knockdown of 48K in HeLa
      cells led to reduced cell growth and the inhibition of U12-type splicing, as well
      as the activation of cryptic, U2-type splice sites, suggesting that 48K plays a
      critical role in U12-type intron recognition. 48K knockdown also led to reduced
      levels of U11/U12 di-snRNP, indicating that 48K contributes to the stability
      and/or formation of this complex. In addition to making contact with the 5'ss,
      48K interacts with the U11-59K protein, a protein at the interface of the U11/U12
      di-snRNP. These studies provide important insights into the protein-mediated
      recognition of the U12-type 5'ss, as well as functionally important interactions
      within the U11/U12 di-snRNP.

PMID- 18347053
TI  - Silencing of Agamma-globin gene expression during adult definitive erythropoiesis
      mediated by GATA-1-FOG-1-Mi2 complex binding at the -566 GATA site.
AB  - Autonomous silencing of gamma-globin transcription is an important developmental
      regulatory mechanism controlling globin gene switching. An adult stage-specific
      silencer of the (A)gamma-globin gene was identified between -730 and -378
      relative to the mRNA start site. A marked copy of the (A)gamma-globin gene
      inserted between locus control region 5' DNase I-hypersensitive site 1 and the
      epsilon-globin gene was transcriptionally silenced in adult beta-globin locus
      yeast artificial chromosome (beta-YAC) transgenic mice, but deletion of the 352
      bp region restored expression. This fragment reduced reporter gene expression in
      K562 cells, and GATA-1 was shown to bind within this sequence at the -566 GATA
      site. Further, the Mi2 protein, a component of the NuRD complex, was observed in
      erythroid cells with low gamma-globin levels, whereas only a weak signal was
      detected when gamma-globin was expressed. Chromatin immunoprecipitation of fetal
      liver tissue from beta-YAC transgenic mice demonstrated that GATA-1, FOG-1, and
      Mi2 were recruited to the (A)gamma-globin -566 or (G)gamma-globin -567 GATA site
      when gamma-globin expression was low (day 18) but not when gamma-globin was
      expressed (day 12). These data suggest that during definitive erythropoiesis,
      gamma-globin gene expression is silenced, in part, by binding a protein complex
      containing GATA-1, FOG-1, and Mi2 at the -566/-567 GATA sites of the proximal
      gamma-globin promoters.

PMID- 18347054
TI  - Stimulation of human and rat islet beta-cell proliferation with retention of
      function by the homeodomain transcription factor Nkx6.1.
AB  - The homeodomain transcription factor Nkx6.1 plays an important role in pancreatic
      islet beta-cell development, but its effects on adult beta-cell function,
      survival, and proliferation are not well understood. In the present study, we
      demonstrated that treatment of primary rat pancreatic islets with a
      cytomegalovirus promoter-driven recombinant adenovirus containing the Nkx6.1 cDNA
      (AdCMV-Nkx6.1) causes dramatic increases in [methyl-(3)H] thymidine and 5-bromo
      2'-deoxyuridine (BrdU) incorporation and in the number of cells per islet
      relative to islets treated with a control adenovirus (AdCMV-betaGAL), whereas
      suppression of Nkx6.1 expression reduces thymidine incorporation.
      Immunocytochemical studies reveal that >80% of BrdU-positive cells in AdCMV
      Nkx6.1-treated islets are beta cells. Microarray, real-time PCR, and immunoblot
      analyses reveal that overexpression of Nkx6.1 in rat islets causes concerted
      upregulation of a cadre of cell cycle control genes, including those encoding
      cyclins A, B, and E, and several regulatory kinases. Cyclin E is upregulated
      earlier than the other cyclins, and adenovirus-mediated overexpression of cyclin
      E is shown to be sufficient to activate islet cell proliferation. Moreover,
      chromatin immunoprecipitation assays demonstrate direct interaction of Nkx6.1
      with the cyclin A2 and B1 genes. Overexpression of Nkx6.1 in rat islets caused a
      clear enhancement of glucose-stimulated insulin secretion (GSIS), whereas
      overexpression of Nkx6.1 in human islets caused an increase in the level of
      [(3)H]thymidine incorporation that was twice the control level, along with
      complete retention of GSIS. We conclude that Nkx6.1 is among the very rare
      factors capable of stimulating beta-cell replication with retention or
      enhancement of function, properties that may be exploitable for expansion of beta
      cell mass in treatment of both major forms of diabetes.

PMID- 18347055
TI  - Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor-
      and toll-like receptor-mediated NF-kappaB activation.
AB  - Stimulation through the interleukin-1 receptor (IL-1R) and some Toll-like
      receptors (TLRs) induces ubiquitination of TRAF6 and IRAK-1, signaling components
      required for NF-kappaB and mitogen-activated protein kinase activation. Here we
      show that although TRAF6 and IRAK-1 acquired Lys63 (K63)-linked polyubiquitin
      chains upon IL-1 stimulation, only ubiquitinated IRAK-1 bound NEMO, the
      regulatory subunit of IkappaB kinase (IKK). The sites of IRAK-1 ubiquitination
      were mapped to Lys134 and Lys180, and arginine substitution of these residues
      impaired IL-1R/TLR-mediated IRAK-1 ubiquitination, NEMO binding, and NF-kappaB
      activation. K63-linked ubiquitination of IRAK-1 required enzymatically active
      TRAF6, indicating that it is the physiologically relevant E3. Thus, K63-linked
      polyubiquitination of proximal signaling proteins is a common mechanism used by
      diverse innate immune receptors for recruiting IKK and activating NF-kappaB.

PMID- 18347056
TI  - Transcription-coupled methylation of histone H3 at lysine 36 regulates dosage
      compensation by enhancing recruitment of the MSL complex in Drosophila
      melanogaster.
AB  - In Drosophila melanogaster, dosage compensation relies on the targeting of the
      male-specific lethal (MSL) complex to hundreds of sites along the male X
      chromosome. Transcription-coupled methylation of histone H3 lysine 36 is enriched
      toward the 3' end of active genes, similar to the MSL proteins. Here, we have
      studied the link between histone H3 methylation and MSL complex targeting using
      RNA interference and chromatin immunoprecipitation. We show that trimethylation
      of histone H3 at lysine 36 (H3K36me3) relies on the histone methyltransferase
      Hypb and is localized promoter distal at dosage-compensated genes, similar to
      active genes on autosomes. However, H3K36me3 has an X-specific function, as
      reduction specifically decreases acetylation of histone H4 lysine 16 on the male
      X chromosome. This hypoacetylation is caused by compromised MSL binding and
      results in a failure to increase expression twofold. Thus, H3K36me3 marks the
      body of all active genes yet is utilized in a chromosome-specific manner to
      enhance histone acetylation at sites of dosage compensation.

PMID- 18347057
TI  - Mutation of the PDK1 PH domain inhibits protein kinase B/Akt, leading to small
      size and insulin resistance.
AB  - PDK1 activates a group of kinases, including protein kinase B (PKB)/Akt, p70
      ribosomal S6 kinase (S6K), and serum and glucocorticoid-induced protein kinase
      (SGK), that mediate many of the effects of insulin as well as other agonists.
      PDK1 interacts with phosphoinositides through a pleckstrin homology (PH) domain.
      To study the role of this interaction, we generated knock-in mice expressing a
      mutant of PDK1 incapable of binding phosphoinositides. The knock-in mice are
      significantly small, insulin resistant, and hyperinsulinemic. Activation of PKB
      is markedly reduced in knock-in mice as a result of lower phosphorylation of PKB
      at Thr308, the residue phosphorylated by PDK1. This results in the inhibition of
      the downstream mTOR complex 1 and S6K1 signaling pathways. In contrast,
      activation of SGK1 or p90 ribosomal S6 kinase or stimulation of S6K1 induced by
      feeding is unaffected by the PDK1 PH domain mutation. These observations
      establish the importance of the PDK1-phosphoinositide interaction in enabling PKB
      to be efficiently activated with an animal model. Our findings reveal how reduced
      activation of PKB isoforms impinges on downstream signaling pathways, causing
      diminution of size as well as insulin resistance.

PMID- 18347058
TI  - The RASSF1A tumor suppressor restrains anaphase-promoting complex/cyclosome
      activity during the G1/S phase transition to promote cell cycle progression in
      human epithelial cells.
AB  - Multiple molecular lesions in human cancers directly collaborate to deregulate
      proliferation and suppress apoptosis to promote tumorigenesis. The candidate
      tumor suppressor RASSF1A is commonly inactivated in a broad spectrum of human
      tumors and has been implicated as a pivotal gatekeeper of cell cycle progression.
      However, a mechanistic account of the role of RASSF1A gene inactivation in tumor
      initiation is lacking. Here we have employed loss-of-function analysis in human
      epithelial cells for a detailed investigation of the contribution of RASSF1 to
      cell cycle progression. We found that RASSF1A has dual opposing regulatory
      connections to G(1)/S phase cell cycle transit. RASSF1A associates with the Ewing
      sarcoma breakpoint protein, EWS, to limit accumulation of cyclin D1 and restrict
      exit from G(1). Surprisingly, we found that RASSF1A is also required to restrict
      SCF(betaTrCP) activity to allow G/S phase transition. This restriction is
      required for accumulation of the anaphase-promoting complex/cyclosome (APC/C)
      inhibitor Emi1 and the concomitant block of APC/C-dependent cyclin A turnover.
      The consequence of this relationship is inhibition of cell cycle progression in
      normal epithelial cells upon RASSF1A depletion despite elevated cyclin D1
      concentrations. Progression to tumorigenicity upon RASSF1A gene inactivation
      should therefore require collaborating genetic aberrations that bypass the
      consequences of impaired APC/C regulation at the G(1)/S phase cell cycle
      transition.

PMID- 18347059
TI  - Integration of protein kinases mTOR and extracellular signal-regulated kinase 5
      in regulating nucleocytoplasmic localization of NFATc4.
AB  - The target of rapamycin (TOR) signaling regulates the nucleocytoplasmic shuttling
      of transcription factors in yeast. Whether the mammalian counterpart of TOR
      (mTOR) also regulates nucleocytoplasmic shuttling is not known. Using a phospho
      specific monoclonal antibody, we demonstrate that mTOR phosphorylates
      Ser(168,170) of endogenous NFATc4, which are conserved gate-keeping Ser residues
      that control NFAT subcellular distribution. The mTOR acts as a basal kinase
      during the resting state to maintain NFATc4 in the cytosol. Inactivation and
      nuclear export of NFATc4 are mediated by rephosphorylation of Ser(168,170), which
      can be a nuclear event. Kinetic analyses demonstrate that rephosphorylation of
      Ser(168,170) of endogenous NFATc4 is mediated by mTOR and, surprisingly, by
      extracellular signal-regulated kinase 5 (ERK5) mitogen-activated protein kinase
      as well. Ablation of ERK5 in the Erk5(-/-) cells ascertains defects in NFATc4
      rephosphorylation and nucleocytoplasmic shuttling. In addition, phosphorylation
      of NFATc4 by ERK5 primes subsequent phosphorylation mediated by CK1alpha. These
      results demonstrate that distinct protein kinases are integrated to phosphorylate
      the gate-keeping residues Ser(168,170) of NFATc4, to regulate subcellular
      distribution. These data also expand the repertoire of physiological substrates
      of mTOR and ERK5.

PMID- 18347060
TI  - The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate
      SNAIL-dependent transcriptional repression.
AB  - The SNAIL transcription factor contains C-terminal tandem zinc finger motifs and
      an N-terminal SNAG repression domain. The members of the SNAIL family have
      recently emerged as major contributors to the processes of development and
      metastasis via the regulation of epithelial-mesenchymal transition events during
      embryonic development and tumor progression. However, the mechanisms by which
      SNAIL represses gene expression are largely undefined. Previously we demonstrated
      that the AJUBA family of LIM proteins function as corepressors for SNAIL and, as
      such, may serve as a platform for the assembly of chromatin-modifying factors.
      Here, we describe the identification of the protein arginine methyltransferase 5
      (PRMT5) as an effector recruited to SNAIL through an interaction with AJUBA that
      functions to repress the SNAIL target gene, E-cadherin. PRMT5 binds to the non
      LIM region of AJUBA and is translocated into the nucleus in a SNAIL- and AJUBA
      dependent manner. The depletion of PRMT5 in p19 cells stimulates E-cadherin
      expression, and the SNAIL, AJUBA, and PRMT5 ternary complex can be found at the
      proximal promoter region of the E-cadherin gene, concomitant with increased
      arginine methylation of histones at the locus. Together, these data suggest that
      PRMT5 is an effector of SNAIL-dependent gene repression.

PMID- 18347061
TI  - p110 CUX1 cooperates with E2F transcription factors in the transcriptional
      activation of cell cycle-regulated genes.
AB  - The transcription factor p110 CUX1 was shown to stimulate cell proliferation by
      accelerating entry into S phase. As p110 CUX1 can function as a transcriptional
      repressor or activator depending on promoter context, we investigated its
      mechanism of transcriptional activation using the DNA polymerase alpha gene
      promoter as a model system. Linker-scanning analysis revealed that a low-affinity
      E2F binding site is required for transcriptional activation. Moreover,
      coexpression with a dominant-negative mutant of DP-1 suggested that endogenous
      E2F factors are indeed needed for p110-mediated activation. Tandem affinity
      purification, coimmunoprecipitation, chromatin immunoprecipitation, and reporter
      assays indicated that p110 CUX1 can engage in weak protein-protein interactions
      with E2F1 and E2F2, stimulate their recruitment to the DNA polymerase alpha gene
      promoter, and cooperate with these factors in transcriptional activation. On the
      other hand, in vitro assays suggested that the interaction between CUX1 and E2F1
      either is not direct or is regulated by posttranslational modifications. Genome
      wide location analysis revealed that targets common to p110 CUX1 and E2F1
      included many genes involved in cell cycle, DNA replication, and DNA repair.
      Comparison of the degree of enrichment for various E2F factors suggested that
      binding of p110 CUX1 to a promoter will favor the specific recruitment of E2F1,
      and to a lesser extent E2F2, over E2F3 and E2F4. Reporter assays on a subset of
      common targets confirmed that p110 CUX1 and E2F1 cooperate in their
      transcriptional activation. Overall, our results show that p110 CUX1 and E2F1
      cooperate in the regulation of many cell cycle genes.

PMID- 18347062
TI  - Requirement of the tissue-restricted homeodomain transcription factor Nkx6.3 in
      differentiation of gastrin-producing G cells in the stomach antrum.
AB  - Many homeodomain transcription factors function in organogenesis and cell
      differentiation. The Nkx family illustrates these functions especially well, and
      the Nkx6 subfamily controls differentiation in the central nervous system and
      pancreas. Nkx6.3, a recent addition to this subfamily, overlaps Nkx6.1 and Nkx6.2
      in expression in the hindbrain and stomach. Nkx6.3 transcripts localize in the
      epithelium of the most distal stomach region, the antrum and pylorus; expression
      in the adult intestine is lower and confined to the proximal duodenum. Nkx6.3(
      )(/)(-) mice develop and grow normally, with a grossly intact stomach and
      duodenum. These mice show markedly reduced gastrin mRNA, many fewer gastrin
      producing (G) cells in the stomach antrum, hypogastrinemia, and increased stomach
      luminal pH, with a corresponding increase in somatostatin mRNA levels and antral
      somatostatin-producing (D) cells. They express normal levels of other
      transcription factors required for gastric endocrine cell differentiation, Pdx1,
      Pax6, and Ngn3; conversely, Ngn3(-)(/)(-) mice, which also show reduced gastrin
      levels, express Nkx6.3 normally. These studies implicate Nkx6.3 as a selective
      regulator of G- and D-cell lineages, which are believed to derive from a common
      progenitor, and suggest that it operates in parallel with Ngn3.

PMID- 18347063
TI  - Cell-type-specific function of BCL9 involves a transcriptional activation domain
      that synergizes with beta-catenin.
AB  - Transcriptional regulation by the canonical Wnt pathway involves the
      stabilization and nuclear accumulation of beta-catenin, which assembles with
      LEF1/TCF transcription factors and cofactors to activate Wnt target genes.
      Recently, the nuclear beta-catenin complex has been shown to contain BCL9, which
      interacts with beta-catenin and recruits Pygopus as a transcriptional
      coactivator. However, the presumed general functions of Pygopus and BCL9, which
      has been proposed to act as a scaffolding protein for Pygopus, have been
      challenged by the rather specific and modest developmental defects of targeted
      inactivations of both the Pygo1 and the Pygo2 genes. Here, we analyze the
      function of BCL9 in transcriptional activation by beta-catenin. We find that BCL9
      acts in a cell-type-specific manner and, in part, independent of Pygopus. We show
      that BCL9 itself contains a transcriptional activation domain in the C terminus,
      which functionally synergizes in lymphoid cells with the C-terminal
      transactivation domain of beta-catenin. Finally, we identify amino acids in the
      transactivation domain of beta-catenin that are important for its function and
      association with the histone acetyltransferases CBP/p300 and TRRAP/GCN5. Thus,
      BCL9 may serve to modulate and diversify the transcriptional responses to Wnt
      signaling in a cell-type-specific manner.

PMID- 18347064
TI  - Protein phosphatase 4 catalytic subunit regulates Cdk1 activity and microtubule
      organization via NDEL1 dephosphorylation.
AB  - Protein phosphatase 4 catalytic subunit (PP4c) is a PP2A-related protein
      serine/threonine phosphatase with important functions in a variety of cellular
      processes, including microtubule (MT) growth/organization, apoptosis, and tumor
      necrosis factor signaling. In this study, we report that NDEL1 is a substrate of
      PP4c, and PP4c selectively dephosphorylates NDEL1 at Cdk1 sites. We also
      demonstrate that PP4c negatively regulates Cdk1 activity at the centrosome.
      Targeted disruption of PP4c reveals disorganization of MTs and disorganized MT
      array. Loss of PP4c leads to an unscheduled activation of Cdk1 in interphase,
      which results in the abnormal phosphorylation of NDEL1. In addition, abnormal
      NDEL1 phosphorylation facilitates excessive recruitment of katanin p60 to the
      centrosome, suggesting that MT defects may be attributed to katanin p60 in
      excess. Inhibition of Cdk1, NDEL1, or katanin p60 rescues the defective MT
      organization caused by PP4 inhibition. Our work uncovers a unique regulatory
      mechanism of MT organization by PP4c through its targets Cdk1 and NDEL1 via
      regulation of katanin p60 distribution.

PMID- 18347065
TI  - Orchestration of the S-phase and DNA damage checkpoint pathways by replication
      forks from early origins.
AB  - The S-phase checkpoint activated at replication forks coordinates DNA replication
      when forks stall because of DNA damage or low deoxyribonucleotide triphosphate
      pools. We explore the involvement of replication forks in coordinating the S
      phase checkpoint using dun1Delta cells that have a defect in the number of
      stalled forks formed from early origins and are dependent on the DNA damage Chk1p
      pathway for survival when replication is stalled. We show that providing
      additional origins activated in early S phase and establishing a paused fork at a
      replication fork pause site restores S-phase checkpoint signaling to chk1Delta
      dun1Delta cells and relieves the reliance on the DNA damage checkpoint pathway.
      Origin licensing and activation are controlled by the cyclin-Cdk complexes. Thus,
      oncogene-mediated deregulation of cyclins in the early stages of cancer
      development could contribute to genomic instability through a deficiency in the
      forks required to establish the S-phase checkpoint.

PMID- 18347066
TI  - An interaction between the SRP receptor and the translocon is critical during
      cotranslational protein translocation.
AB  - The signal recognition particle (SRP)-dependent targeting pathway facilitates
      rapid, efficient delivery of the ribosome-nascent chain complex (RNC) to the
      protein translocation channel. We test whether the SRP receptor (SR) locates a
      vacant protein translocation channel by interacting with the yeast Sec61 and Ssh1
      translocons. Surprisingly, the slow growth and cotranslational translocation
      defects caused by deletion of the transmembrane (TM) span of yeast SRbeta (SRbeta
      DeltaTM) are exaggerated when the SSH1 gene is disrupted. Disruption of the SBH2
      gene, which encodes the beta subunit of the Ssh1p complex, likewise causes a
      growth defect when combined with SRbeta-DeltaTM. Cotranslational translocation
      defects in the ssh1DeltaSRbeta-DeltaTM mutant are explained by slow and
      inefficient in vivo gating of translocons by RNCs. A critical function for
      translocation channel beta subunits in the SR-channel interaction is supported by
      the observation that simultaneous deletion of Sbh1p and Sbh2p causes a defect in
      the cotranslational targeting pathway that is similar to the translocation defect
      caused by deletion of either subunit of the SR.

PMID- 18347067
TI  - Distinct acto/myosin-I structures associate with endocytic profiles at the plasma
      membrane.
AB  - Endocytosis in yeast requires actin and clathrin. Live cell imaging has
      previously shown that massive actin polymerization occurs concomitant with a slow
      200-nm inward movement of the endocytic coat (Kaksonen, M., Y. Sun, and D.G.
      Drubin. 2003. Cell. 115:475-487). However, the nature of the primary endocytic
      profile in yeast and how clathrin and actin cooperate to generate an endocytic
      vesicle is unknown. In this study, we analyze the distribution of nine different
      proteins involved in endocytic uptake along plasma membrane invaginations using
      immunoelectron microscopy. We find that the primary endocytic profiles are
      tubular invaginations of up to 50 nm in diameter and 180 nm in length, which
      accumulate the endocytic coat components at the tip. Interestingly, significant
      actin labeling is only observed on invaginations longer than 50 nm, suggesting
      that initial membrane bending occurs before initiation of the slow inward
      movement. We also find that in the longest profiles, actin and the myosin-I Myo5p
      form two distinct structures that might be implicated in vesicle fission.

PMID- 18347068
TI  - Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine
      phosphorylated caveolin-1.
AB  - Both tyrosine-phosphorylated caveolin-1 (pY14Cav1) and GlcNAc-transferase V
      (Mgat5) are linked with focal adhesions (FAs); however, their function in this
      context is unknown. Here, we show that galectin-3 binding to Mgat5-modified N
      glycans functions together with pY14Cav1 to stabilize focal adhesion kinase (FAK)
      within FAs, and thereby promotes FA disassembly and turnover. Expression of the
      Mgat5/galectin lattice alone induces FAs and cell spreading. However, FAK
      stabilization in FAs also requires expression of pY14Cav1. In cells lacking the
      Mgat5/galectin lattice, pY14Cav1 is not sufficient to promote FAK stabilization,
      FA disassembly, and turnover. In human MDA-435 cancer cells, Cav1 expression, but
      not mutant Y14FCav1, stabilizes FAK exchange and stimulates de novo FA formation
      in protrusive cellular regions. Thus, transmembrane crosstalk between the
      galectin lattice and pY14Cav1 promotes FA turnover by stabilizing FAK within FAs
      defining previously unknown, interdependent roles for galectin-3 and pY14Cav1 in
      tumor cell migration.

PMID- 18347069
TI  - As functional nuclear actin comes into view, is it globular, filamentous, or
      both?
AB  - The idea that actin may have an important function in the nucleus has undergone a
      rapid transition from one greeted with skepticism to a now rapidly advancing
      research field. Actin has now been implicated in transcription by all three RNA
      polymerases, but the structural form it adopts in these processes remains
      unclear. Recently, a claim was made that monomeric nuclear actin plays a role in
      signal transduction, while a just-published study of RNA polymerase I
      transcription has implicated polymeric actin, consorting with an isoform of its
      classical partner myosin. Both studies are critically discussed here, and
      although there are several issues to be resolved, it now seems reasonable to
      start thinking about functions for both monomeric and assembled actin in the
      nucleus.

PMID- 18347070
TI  - Shuttling of the chaperones Unc45b and Hsp90a between the A band and the Z line
      of the myofibril.
AB  - The formation of thick filaments in striated muscle involves the chaperones
      Hsp90a and Unc45. We show that Unc45b and Hsp90a, two zebrafish orthologues,
      colocalize with myosin during myofibrillogenesis and associate with the Z line
      when myofibril assembly is completed. In response to stress or damage to the
      myofiber, Unc45b and Hsp90a dissociate from the Z line and transiently associate
      with myosin. Although chaperone activity of Unc45b requires the full-length
      protein, only the central and Unc45-Cro1p-She4p domains are required to anchor it
      to the Z line, and multiple subdomains mediate association with nascent myosin.
      We propose that the Z line serves as a reservoir for chaperones, allowing a rapid
      mobilization in response to muscle damage. Our data are consistent with a
      differential affinity model as an explanation for the shuttling of the chaperones
      between the Z line and myosin.

PMID- 18347071
TI  - Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization
      of beta-catenin-TCF interaction.
AB  - In canonical Wnt signaling, Dishevelled (Dvl) is a critical cytoplasmic regulator
      that releases beta-catenin from degradation. Here, we find that Dvl and c-Jun
      form a complex with beta-catenin-T-cell factor 4 (TCF-4) on the promoter of Wnt
      target genes and regulate gene transcription. The complex forms via two
      interactions of nuclear Dvl with c-Jun and beta-catenin, respectively, both of
      which bind to TCF. Disrupting the interaction of Dvl with either c-Jun or beta
      catenin suppresses canonical Wnt signaling-stimulated transcription, and the
      reduction of Dvl diminished beta-catenin-TCF-4 association on Wnt target gene
      promoters in vivo. Expression of a TCF-Dvl fusion protein largely rescued the c
      Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we
      confirm that c-Jun functions in canonical Wnt signaling and show that c-Jun
      functions as a scaffold in the beta-catenin-TCFs transcription complex bridging
      Dvl to TCF. Our results reveal a mechanism by which nuclear Dvl cooperates with c
      Jun to regulate gene transcription stimulated by the canonical Wnt signaling
      pathway.

PMID- 18347072
TI  - Dynamics of inner kinetochore assembly and maintenance in living cells.
AB  - To investigate the dynamics of centromere organization, we have assessed the
      exchange rates of inner centromere proteins (CENPs) by quantitative microscopy
      throughout the cell cycle in human cells. CENP-A and CENP-I are stable centromere
      components that are incorporated into centromeres via a "loading-only" mechanism
      in G1 and S phase, respectively. A subfraction of CENP-H also stays stably bound
      to centromeres. In contrast, CENP-B, CENP-C, and some CENP-H and hMis12 exhibit
      distinct and cell cycle-specific centromere binding stabilities, with residence
      times ranging from seconds to hours. CENP-C and CENP-H are immobilized at
      centromeres specifically during replication. In mitosis, all inner CENPs become
      completely immobilized. CENPs are highly mobile throughout bulk chromatin, which
      is consistent with a binding-diffusion behavior as the mechanism to scan for
      vacant high-affinity binding sites at centromeres. Our data reveal a wide range
      of cell cycle-specific assembly plasticity of the centromere that provides both
      stability through sustained binding of some components and flexibility through
      dynamic exchange of other components.

PMID- 18347073
TI  - Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for
      the formation of protein aggregates in adult brain.
AB  - P62 has been proposed to mark ubiquitinated protein bodies for autophagic
      degradation. We report that the Drosophila melanogaster p62 orthologue, Ref(2)P,
      is a regulator of protein aggregation in the adult brain. We demonstrate that
      Ref(2)P localizes to age-induced protein aggregates as well as to aggregates
      caused by reduced autophagic or proteasomal activity. A similar localization to
      protein aggregates is also observed in D. melanogaster models of human
      neurodegenerative diseases. Although atg8a autophagy mutant flies show
      accumulation of ubiquitin- and Ref(2)P-positive protein aggregates, this is
      abrogated in atg8a/ref(2)P double mutants. Both the multimerization and ubiquitin
      binding domains of Ref(2)P are required for aggregate formation in vivo. Our
      findings reveal a major role for Ref(2)P in the formation of ubiquitin-positive
      protein aggregates both under physiological conditions and when normal protein
      turnover is inhibited.

PMID- 18347074
TI  - Role of protease-activated receptors in inflammatory responses, innate and
      adaptive immunity.
AB  - Serine proteases are well known as enzymes involved in digestion of dietary
      proteins, blood coagulation, and homeostasis. Only recent groundbreaking studies
      revealed a novel role of serine proteases as signaling molecules acting via
      protease-activated receptors (PARs). Important effects of PAR activation on
      leukocyte motility, cytokine production, adhesion molecule expression, and a
      variety of other physiological or pathophysiological functions have been
      described in vitro and in vivo. The crucial role of PAR activation during disease
      progression was revealed in animal models of different gastrointestinal
      pathologies, neuroinflammatory and neurodegenerative processes, skin, joint and
      airway inflammation, or allergic responses. This review focuses on the findings
      related to the impact of PAR deficiency in animal models of inflammatory and
      allergic diseases. Additionally, we observe the role of PAR activation in the
      regulation of functional responses of innate and adaptive immune cells in vitro.
      Understanding the mechanisms by which PARs exert the effects of serine proteases
      on immune cells may lead to new therapeutic strategies in inflammation, immune
      defense, and allergy.

PMID- 18347075
TI  - Pregnancy enhances the innate immune response in experimental cutaneous
      leishmaniasis through hormone-modulated nitric oxide production.
AB  - The maintenance of host defense during pregnancy may depend on heightened innate
      immunity. We evaluated the immune response of pregnant hamsters during early
      infection with Leishmania (Viannia) panamensis, a cause of American cutaneous
      leishmaniasis. At 7 days post-infection, pregnant animals showed a lower parasite
      burden compared with nonpregnant controls at the cutaneous infection site
      (P=0.0098) and draining lymph node (P=0.02). Resident peritoneal macrophages and
      neutrophils from pregnant animals had enhanced Leishmania killing capacity
      compared with nonpregnant controls (P=0.018 each). This enhanced resistance
      during pregnancy was associated with increased expression of inducible NO
      synthase (iNOS) mRNA in lymph node cells (P=0.02) and higher NO production by
      neutrophils (P=0.0001). Macrophages from nonpregnant hamsters infected with L.
      panamensis released high amounts of NO upon estrogen exposure (P=0.05), and
      addition of the iNOS inhibitor L-N6-(1-iminoethyl) lysine blocked the induction
      of NO production (P=0.02). Infected, nonpregnant females treated with estrogen
      showed a higher percentage of cells producing NO at the infection site than
      controls (P=0.001), which correlated with lower parasite burdens (P=0.036).
      Cultured macrophages or neutrophils from estrogen-treated hamsters showed
      significantly increased NO production and Leishmania killing compared with
      untreated controls. iNOS was identified as the likely source of estrogen-induced
      NO in primed and naive macrophages, as increased transcription was evident by
      real-time PCR. Thus, the innate defense against Leishmania infection is
      heightened during pregnancy, at least in part as a result of estrogen-mediated up
      regulation of iNOS expression and NO production.

PMID- 18347076
TI  - Characteristics of the phagocytic cup induced by uropathogenic Escherichia coli.
AB  - Uropathogenic Escherichia coli invade the urothelial umbrella cells by using the
      zipper mechanism. However, the details of the early events of this invasion, such
      as the formation of the phagocytic cup, are not yet well understood. We show
      here, using thin section electron microscopy and immunogold labeling, that the
      plasma membrane curves around the bacterial surface in the phagocytic cup. There
      exists a uniform gap between the bacterium and the urothelial membrane, and actin
      filaments are present in the phagocytic cup. We suggest that the action-reaction
      between the mechanical forces generated by pilus retraction of the bacterium and
      the actin polymerization in the urothelial cell plays a role in maintaining the
      phagocytic cup. This manuscript contains online supplemental material at
      http://www.jhc.org. Please visit this article online to view these materials.

PMID- 18347077
TI  - Mesothelin expression in the leptomeninges and meningiomas.
AB  - The identity and functions of surface proteins on human leptomeningeal and
      meningioma cells are incompletely characterized. Some structural and functional
      similarities between the leptomeninges and pleura suggest that proteins important
      to pleural function and tumorigenesis might also be relevant to leptomeningeal
      disease. Mesothelin is a recently described, 40-kDa membrane protein expressed in
      pleura. Its functions in this tissue are under investigation. Sections of 20
      normal adult brains with leptomeninges and 49 World Health Organization (WHO)
      grade I, 21 grade II, and 2 grade III meningiomas were analyzed using an
      extensively characterized monoclonal antibody to mesothelin and streptavidin
      biotin complex immunohistochemistry. Five meningiomas were also evaluated by
      Western blot. Mesothelin immunoreactivity was detected in the arachnoid in 6 of
      20 cases and in 23 of 49 WHO grade I meningiomas. It was also detected in 7 of 21
      WHO II tumors and 1 of the 2 anaplastic meningiomas. By Western blot, all five
      meningiomas exhibited mesothelin precursor protein, including one where notable
      immunoreactivity was not identified in a formalin-fixed tissue section. These
      findings suggest that mesothelin is expressed in at least some arachnoid and
      meningioma cells. Future studies may clarify its role in the development of
      meningiomas, meningeal seeding of gliomas, and metastases to the leptomeninges.

PMID- 18347078
TI  - Generation and characterization of Ptf1a antiserum and localization of Ptf1a in
      relation to Nkx6.1 and Pdx1 during the earliest stages of mouse pancreas
      development.
AB  - Ptf1a and Pdx1 are critical transcription factors of early pancreatic
      development, as shown by loss of function studies where lack of each gene alone
      causes almost complete pancreas agenesis. Ptf1a is particularly interesting
      because it is linked to a recently reported signature gene expression profile
      associated with the multipotent condition. Few useful antibody reagents have been
      available for consistent and reliable immunohistochemical visualization of Ptf1a
      protein expression in the early developing pancreas in which the level of
      production of this critical regulator seems to be very low. We describe a novel
      rabbit antibody raised against the c-terminal portion of the mouse Ptf1a protein
      and report immunodetection, for the first time, as early as embryonic day (e) 8.5
      e8.75 in the dorsal and ventral buds of the mouse pancreas as well as in the
      neural tube at e10.0. Detailed confocal analysis identifies an abundant triple
      positive (Ptf1a(+)/Nkx6.1(+)/Pdx1(+)) putative early multipotent pancreatic
      progenitor cell that marks the e9.5 dorsal pancreas and e10.5 ventral pancreas.
      Furthermore, expression patterns of Nkx6.1 vs Ptf1a subsequently segregate during
      branching morphogenesis (trunk vs tip), ending up marking two distinct cell
      populations of progenitors at e12.5. From e15.5 (mouse) and in adult pancreas
      (mouse, rat, and human), the Ptf1a antibody marks only acinar cell nuclei, as
      expected for its subsequent role in committing/maintaining cells in this
      differentiated state. In summary, this antibody is a novel tool to further
      characterize important early steps of pancreas differentiation. This manuscript
      contains online supplemental material at http://www.jhc.org. Please visit this
      article online to view these materials.

PMID- 18347079
TI  - Calcium-dependent inactivation terminates calcium release in skeletal muscle of
      amphibians.
AB  - In skeletal muscle of amphibians, the cell-wide cytosolic release of calcium that
      enables contraction in response to an action potential appears to be built of
      Ca2+ sparks. The mechanism that rapidly terminates this release was investigated
      by studying the termination of Ca2+ release underlying sparks. In groups of
      thousands of sparks occurring spontaneously in membrane-permeabilized frog muscle
      cells a complex relationship was found between amplitude a and rise time T, which
      in sparks corresponds to the active time of the underlying Ca2+ release. This
      relationship included a range of T where a paradoxically decreased with
      increasing T. Three different methods were used to estimate Ca2+ release flux in
      groups of sparks of different T. Using every method, it was found that T and flux
      were inversely correlated, roughly inversely proportional. A simple model in
      which release sources were inactivated by cytosolic Ca2+ was able to explain the
      relationship. The predictive value of the model, evaluated by analyzing the
      variance of spark amplitude, was found to be high when allowance was made for the
      out-of-focus error contribution to the total variance. This contribution was
      estimated using a theory of confocal scanning (Rios, E., N. Shirokova, W.G.
      Kirsch, G. Pizarro, M.D. Stern, H. Cheng, and A. Gonzalez. Biophys. J. 2001.
      80:169-183), which was confirmed in the present work by simulated line scanning
      of simulated sparks. Considering these results and other available evidence it is
      concluded that Ca2+-dependent inactivation, or CDI, provides the crucial
      mechanism for termination of sparks and cell-wide Ca2+ release in amphibians.
      Given the similarities in kinetics of release termination observed in cell
      averaged records of amphibian and mammalian muscle, and in spite of differences
      in activation mechanisms, CDI is likely to play a central role in mammals as
      well. Trivially, an inverse proportionality between release flux and duration, in
      sparks or in global release of skeletal muscle, maintains constancy of the amount
      of released Ca2+.

PMID- 18347080
TI  - Roles of GRK and PDE4 activities in the regulation of beta2 adrenergic signaling.
AB  - An important focus in cell biology is understanding how different feedback
      mechanisms regulate G protein-coupled receptor systems. Toward this end we
      investigated the regulation of endogenous beta(2) adrenergic receptors (beta2ARs)
      and phosphodiesterases (PDEs) by measuring cAMP signals in single HEK-293 cells.
      We monitored cAMP signals using genetically encoded cyclic nucleotide-gated (CNG)
      channels. This high resolution approach allowed us to make several observations.
      (a) Exposure of cells to 1 muM isoproterenol triggered transient increases in
      cAMP levels near the plasma membrane. Pretreatment of cells with 10 muM rolipram,
      a PDE4 inhibitor, prevented the decline in the isoproterenol-induced cAMP
      signals. (b) 1 muM isoproterenol triggered a sustained, twofold increase in
      phosphodiesterase type 4 (PDE4) activity. (c) The decline in isoproterenol
      dependent cAMP levels was not significantly altered by including 20 nM PKI, a PKA
      inhibitor, or 3 muM 59-74E, a GRK inhibitor, in the pipette solution; however,
      the decline in the cAMP levels was prevented when both PKI and 59-74E were
      included in the pipette solution. (d) After an initial 5-min stimulation with
      isoproterenol and a 5-min washout, little or no recovery of the signal was
      observed during a second 5-min stimulation with isoproterenol. (e) The amplitude
      of the signal in response to the second isoproterenol stimulation was not altered
      when PKI was included in the pipette solution, but was significantly increased
      when 59-74E was included. Taken together, these data indicate that either GRK
      mediated desensitization of beta2ARs or PKA-mediated stimulation of PDE4 activity
      is sufficient to cause declines in cAMP signals. In addition, the data indicate
      that GRK-mediated desensitization is primarily responsible for a sustained
      suppression of beta2AR signaling. To better understand the interplay between
      receptor desensitization and PDE4 activity in controlling cAMP signals, we
      developed a mathematical model of this system. Simulations of cAMP signals using
      this model are consistent with the experimental data and demonstrate the
      importance of receptor levels, receptor desensitization, basal adenylyl cyclase
      activity, and regulation of PDE activity in controlling cAMP signals, and hence,
      on the overall sensitivity of the system.

PMID- 18347081
TI  - Luminal Ca2+ regulation of single cardiac ryanodine receptors: insights provided
      by calsequestrin and its mutants.
AB  - The luminal Ca2+ regulation of cardiac ryanodine receptor (RyR2) was explored at
      the single channel level. The luminal Ca2+ and Mg2+ sensitivity of single CSQ2
      stripped and CSQ2-associated RyR2 channels was defined. Action of wild-type CSQ2
      and of two mutant CSQ2s (R33Q and L167H) was also compared. Two luminal Ca2+
      regulatory mechanism(s) were identified. One is a RyR2-resident mechanism that is
      CSQ2 independent and does not distinguish between luminal Ca2+ and Mg2+. This
      mechanism modulates the maximal efficacy of cytosolic Ca2+ activation. The second
      luminal Ca2+ regulatory mechanism is CSQ2 dependent and distinguishes between
      luminal Ca2+ and Mg2+. It does not depend on CSQ2 oligomerization or CSQ2 monomer
      Ca2+ binding affinity. The key Ca2+-sensitive step in this mechanism may be the
      Ca2+-dependent CSQ2 interaction with triadin. The CSQ2-dependent mechanism alters
      the cytosolic Ca2+ sensitivity of the channel. The R33Q CSQ2 mutant can
      participate in luminal RyR2 Ca2+ regulation but less effectively than wild-type
      (WT) CSQ2. CSQ2-L167H does not participate in luminal RyR2 Ca2+ regulation. The
      disparate actions of these two catecholaminergic polymorphic ventricular
      tachycardia (CPVT)-linked mutants implies that either alteration or elimination
      of CSQ2-dependent luminal RyR2 regulation can generate the CPVT phenotype. We
      propose that the RyR2-resident, CSQ2-independent luminal Ca2+ mechanism may
      assure that all channels respond robustly to large (>5 muM) local cytosolic Ca2+
      stimuli, whereas the CSQ2-dependent mechanism may help close RyR2 channels after
      luminal Ca2+ falls below approximately 0.5 mM.

PMID- 18347082
TI  - Calcium transport mechanisms of PC12 cells.
AB  - Many studies of Ca2+ signaling use PC12 cells, yet the balance of Ca2+ clearance
      mechanisms in these cells is unknown. We used pharmacological inhibition of Ca2+
      transporters to characterize Ca2+ clearance after depolarizations in both
      undifferentiated and nerve growth factor-differentiated PC12 cells. Sarco
      endoplasmic reticulum Ca2+ ATPase (SERCA), plasma membrane Ca2+ ATPase (PMCA),
      and Na+/Ca2+ exchanger (NCX) account for almost all Ca2+ clearance in both cell
      states, with NCX and PMCA making the greatest contributions. Any contribution of
      mitochondrial uniporters is small. The ATP pool in differentiated cells was much
      more labile than that of undifferentiated cells in the presence of agents that
      dissipated mitochondrial proton gradients. Differentiated PC12 cells have a small
      component of Ca2+ clearance possessing pharmacological characteristics consistent
      with secretory pathway Ca2+ ATPase (SPCA), potentially residing on Golgi and/or
      secretory granules. Undifferentiated and differentiated cells are similar in
      overall Ca2+ transport and in the small transport due to SERCA, but they differ
      in the fraction of transport by PMCA and NCX. Transport in neurites of
      differentiated PC12 cells was qualitatively similar to that in the somata, except
      that the ER stores in neurites sometimes released Ca2+ instead of clearing it
      after depolarization. We formulated a mathematical model to simulate the observed
      Ca2+ clearance and to describe the differences between these undifferentiated and
      NGF-differentiated states quantitatively. The model required a value for the
      endogenous Ca2+ binding ratio of PC12 cell cytoplasm, which we measured to be 268
      +/- 85. Our results indicate that Ca2+ transport in undifferentiated PC12 cells
      is quite unlike transport in adrenal chromaffin cells, for which they often are
      considered models. Transport in both cell states more closely resembles that of
      sympathetic neurons, for which differentiated PC12 cells often are considered
      models. Comparison with other cell types shows that different cells emphasize
      different Ca2+ transport mechanisms.

PMID- 18347083
TI  - Long-term functional stability of human HepaRG hepatocytes and use for chronic
      toxicity and genotoxicity studies.
AB  - The human hepatoma HepaRG cells are able to differentiate in vitro into
      hepatocyte-like cells and to express various liver-specific functions, including
      the major cytochromes P450. This study was aimed to determine whether
      differentiated HepaRG cells retained their specific functional capacities for a
      long time period at confluence. We show that expression of transcripts encoding
      CYP1A2, 2B6, 3A4, and 2E1, several phase II and antioxidant enzymes, membrane
      transporters, including organic cation transporter 1 and bile salt export pump,
      the nuclear receptors constitutive androstane receptor and pregnane X receptor,
      and aldolase B remained relatively stable for at least the 4-week confluence
      period tested. Similarly, activities of CYP3A4 and CYP1A2 and their
      responsiveness to prototypical inducers were well preserved. Aflatoxin B(1), a
      potent hepatotoxicant and carcinogen, induced a dose-dependent and cumulative
      cytotoxicity. Furthermore, at a concentration as low as 0.1 microM, this
      mycotoxin caused a decrease in both CYP3A4 activity and intracellular ATP
      associated with morphological alterations, after 14 days following every 2-day
      exposure. Moreover, using the comet assay, a dose-dependent DNA damage was
      observed after a 3-h treatment of differentiated HepaRG cells with 1 to 5 microM
      aflatoxin B(1) in the absence of any cell damage, and this DNA damaging effect
      was strongly reduced in the presence of ketoconazole, a CYP3A4 inhibitor. These
      results bring the first demonstration of long-term stable expression of liver
      specific markers in HepaRG hepatocyte cultures maintained at confluence and show
      that these cells represent a suitable in vitro liver cell model for analysis of
      acute and chronic toxicity as well as genotoxicity of chemicals in human liver.

PMID- 18347084
TI  - Comparison of two immortalized human cell lines to study nuclear receptor
      mediated CYP3A4 induction.
AB  - Since CYP3A4 is responsible for the biotransformation of over 50% of all
      clinically used drugs, induction results in an increased clearance of many
      concomitantly administered drugs, thereby decreasing treatment efficacy or, in
      the case of prodrugs, lead to severe intoxications. CYP3A4 induction is regulated
      by the pregnane X receptor, constitutive androstane receptor, and vitamin D
      receptor. Since these nuclear receptors show large interspecies differences,
      accurate prediction of nuclear receptor-mediated CYP3A4 induction in humans
      requires the use of human systems. Because primary cultures of human hepatocytes
      or enterocytes have major drawbacks like poor availability and poor
      reproducibility, human cell lines are a good alternative. In this study, the
      widely used HepG2 cell line was compared with the LS180 cell line to serve as a
      model to study CYP3A4 induction. There was a clear difference between the cell
      lines with respect to CYP3A enzyme expression and induction. In LS180, CYP3A4 was
      expressed and was found to be induced by prototypical nuclear receptor agonists,
      whereas in HepG2, CYP3A4 was nonresponsive to treatment with rifampicin, CITCO [6
      (4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-3,4-dichlorobenzyl)
      oxime], or calcitriol. We subsequently evaluated whether these host-cell
      differences also have an effect on CYP3A4 reporter gene activity. We clearly show
      that there are differences in CYP3A4 reporter activity between the cell lines,
      and based on these results and those found on mRNA and protein level, we conclude
      that LS180 is a more suitable cell line to study CYP3A4 induction than the widely
      used HepG2.

PMID- 18347085
TI  - Role of P-glycoprotein and the intestine in the excretion of DPC 333 [(2R)-2
      {(3R)-3-amino-3-[4-(2-methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N
      hydroxy-4-methylpentanamide] in rodents.
AB  - The role of the intestine in the elimination of (2R)-2-{(3R)-3-amino-3-[4-(2
      methylquinolin-4-ylmethoxy)phenyl]-2-oxopyrrolidin-1-yl}-N-hydroxy-4
      methylpentanamide (DPC 333), a potent inhibitor of tissue necrosis factor alpha
      converting enzyme, was investigated in mice and rats in vivo and in vitro. In
      Madine-Darby canine kidney cells stably transfected with P-glycoprotein (P-gp)
      and DPC 333, the transport from B-->A reservoirs exceeded the transport from A-
      >B by approximately 7-fold. In Caco-2 monolayers and isolated rat ileal mucosa,
      DPC 333 was transported from basolateral to apical reservoirs in a concentration
      dependent, saturable manner, and transport was blocked by N-(4-[2-(1,2,3,4
      tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9
      oxo-4-acridine carboxamide (GF120918), confirming the contribution of P-gp/breast
      cancer resistance protein in B-->A efflux of DPC 333. In quantitative whole body
      autoradiography studies with [(14)C]DPC 333 in mice and rats, radioactivity was
      distributed throughout the small intestine in both species. In GF120918
      pretreated bile duct-cannulated rats, radioactivity in feces was reduced 60%.
      Using the in situ perfused rat intestine model, approximately 20% of an i.v. dose
      of [(14)C]DPC 333 was measured in the intestinal lumen within 3 h postdose, 12%
      as parent. Kinetic analysis of data suggested that excreted DPC 333 may be
      further metabolized in the gut. Intestinal clearance was 0.2 to 0.35 l/h/kg. The
      above data suggest that in the rodent the intestine serves as an organ of DPC 333
      excretion, mediated in part by the transporter P-gp.

PMID- 18347086
TI  - BMPs oppose Math1 in cerebellar development and in medulloblastoma.

PMID- 18347087
TI  - Micromanaging regeneration.

PMID- 18347088
TI  - A house with many rooms: how the heart got its chambers with foxn4.

PMID- 18347089
TI  - Interpretation of cytokine signaling through the transcription factors STAT5A and
      STAT5B.
AB  - Transcription factors from the family of Signal Transducers and Activators of
      Transcription (STAT) are activated by numerous cytokines. Two members of this
      family, STAT5A and STAT5B (collectively called STAT5), have gained prominence in
      that they are activated by a wide variety of cytokines such as interleukins,
      erythropoietin, growth hormone, and prolactin. Furthermore, constitutive STAT5
      activation is observed in the majority of leukemias and many solid tumors.
      Inactivation studies in mice as well as human mutations have provided insight
      into many of STAT5's functions. Disruption of cytokine signaling through STAT5
      results in a variety of cell-specific effects, ranging from a defective immune
      system and impaired erythropoiesis, the complete absence of mammary development
      during pregnancy, to aberrant liver function. On a molecular level, STAT5 has
      been linked to cell specification, proliferation, differentiation, and survival.
      Evidence is growing that the diverse outcomes of STAT5 signaling are not only
      determined by the expression of specific receptors but also by the interaction of
      STAT5 with cofactors and the cell-specific activity of members of the SOCS
      family, which negatively regulate STAT function. In this review, we focus on
      emerging concepts and challenges in the field of Janus kinase (JAK)-STAT5
      signaling. First, we discuss unique functions of STAT5 in three distinct systems:
      mammary epithelial cells, hepatocytes, and regulatory T cells. Second, we present
      an example of how STAT5 can achieve cell specificity in hepatocytes through a
      physical and functional interaction with the glucocorticoid receptor. Third, we
      focus on the relevance of STAT5 in the development and progression of leukemia.
      Next, we discuss lessons derived from human mutations and disease. Finally, we
      address an emerging issue that the interpretation of experiments from STAT5
      deficient mice and cells might be compromised as these cells might reroute and
      reprogram cytokine signals to the "wrong" STATs and thus acquire inappropriate
      cues. We propose that mice with mutations in various components of the JAK-STAT
      signaling pathway are living laboratories, which will provide insight into the
      versatility of signaling hardware and the adaptability of the software.

PMID- 18347090
TI  - Post-transcriptional down-regulation of Atoh1/Math1 by bone morphogenic proteins
      suppresses medulloblastoma development.
AB  - Bone morphogenic proteins 2 and 4 (BMP2 and BMP4) inhibit proliferation and
      induce differentiation of cerebellar granule neuron progenitors (GNPs) and
      primary GNP-like medulloblastoma (MB) cells. This occurs through rapid proteasome
      mediated degradation of Math1 (Atoh1), a transcription factor expressed in
      proliferating GNPs. Ectopic expression of Atoh1, but not of Sonic hedgehog (Shh)
      regulated Gli1 or Mycn, cancels these BMP-mediated effects and restores Shh
      dependent proliferation of GNPs and MB cells in vitro and in vivo. Genes
      regulating the BMP signaling pathway are down-regulated in mouse MBs. Thus, BMPs
      are potent inhibitors of MB and should be considered as novel therapeutic agents.

PMID- 18347091
TI  - Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in
      zebrafish.
AB  - Appendage regeneration is defined by rapid changes in gene expression that
      achieve dramatic developmental effects, suggesting involvement of microRNAs
      (miRNAs). Here, we find dynamic regulation of many miRNAs during zebrafish fin
      regeneration. In particular, miR-133 levels are high in uninjured fins but low
      during regeneration. When regeneration was blocked by Fibroblast growth factor
      (Fgf) receptor inhibition, high miR-133 levels were quickly restored.
      Experimentally increasing amounts of miR-133 attenuated fin regeneration.
      Conversely, miR-133 antagonism during Fgf receptor inhibition accelerated
      regeneration through increased proliferation within the regeneration blastema.
      The Mps1 kinase, an established positive regulator of blastemal proliferation, is
      an in vivo target of miR-133. Our findings identify miRNA depletion as a new
      regulatory mechanism for complex tissue regeneration.

PMID- 18347092
TI  - Foxn4 directly regulates tbx2b expression and atrioventricular canal formation.
AB  - Cardiac chamber formation represents an essential evolutionary milestone that
      allows for the heart to receive (atrium) and pump (ventricle) blood throughout a
      closed circulatory system. Here, we reveal a novel transcriptional pathway
      between foxn4 and tbx genes that facilitates this evolutionary event. We show
      that the zebrafish gene slipjig, which encodes Foxn4, regulates the formation of
      the atrioventricular (AV) canal to divide the heart. sli/foxn4 is expressed in
      the AV canal, and its encoded product binds to a highly conserved tbx2 enhancer
      domain that contains Foxn4- and T-box-binding sites, both necessary to regulate
      tbx2b expression in the AV canal.

PMID- 18347093
TI  - Cooperative regulation in development by SMRT and FOXP1.
AB  - A critical aspect of mammalian development involves the actions of dedicated
      repressors/corepressors to prevent unregulated gene activation programs that
      would initiate specific cell determination events. While the role of NCoR/SMRT
      corepressors in nuclear receptor actions is well documented, we here report that
      a previously unrecognized functional interaction between SMRT and a forkhead
      protein, FOXP1, is required for cardiac growth and regulation of macrophage
      differentiation. Our studies demonstrate that SMRT and FOXP1 define a functional
      biological unit required to orchestrate specific programs critical for mammalian
      organogenesis, linking developmental roles of FOX to a specific corepressor.

PMID- 18347094
TI  - Tcf3 is an integral component of the core regulatory circuitry of embryonic stem
      cells.
AB  - Embryonic stem (ES) cells have a unique regulatory circuitry, largely controlled
      by the transcription factors Oct4, Sox2, and Nanog, which generates a gene
      expression program necessary for pluripotency and self-renewal. How external
      signals connect to this regulatory circuitry to influence ES cell fate is not
      known. We report here that a terminal component of the canonical Wnt pathway in
      ES cells, the transcription factor T-cell factor-3 (Tcf3), co-occupies promoters
      throughout the genome in association with the pluripotency regulators Oct4 and
      Nanog. Thus, Tcf3 is an integral component of the core regulatory circuitry of ES
      cells, which includes an autoregulatory loop involving the pluripotency
      regulators. Both Tcf3 depletion and Wnt pathway activation cause increased
      expression of Oct4, Nanog, and other pluripotency factors and produce ES cells
      that are refractory to differentiation. Our results suggest that the Wnt pathway,
      through Tcf3, brings developmental signals directly to the core regulatory
      circuitry of ES cells to influence the balance between pluripotency and
      differentiation.

PMID- 18347095
TI  - A natural antisense transcript regulates Zeb2/Sip1 gene expression during Snail1
      induced epithelial-mesenchymal transition.
AB  - Expression of Snail1 in epithelial cells triggers an epithelial-mesenchymal
      transition (EMT). Here, we demonstrate that the synthesis of Zeb2, a
      transcriptional repressor of E-cadherin, is up-regulated after Snail1-induced
      EMT. Snail1 does not affect the synthesis of Zeb2 mRNA, but prevents the
      processing of a large intron located in its 5'-untranslated region (UTR). This
      intron contains an internal ribosome entry site (IRES) necessary for the
      expression of Zeb2. Maintenance of 5'-UTR Zeb2 intron is dependent on the
      expression of a natural antisense transcript (NAT) that overlaps the 5' splice
      site in the intron. Ectopic overexpression of this NAT in epithelial cells
      prevents splicing of the Zeb2 5'-UTR, increases the levels of Zeb2 protein, and
      consequently down-regulates E-cadherin mRNA and protein. The relevance of these
      results is demonstrated by the strong association between NAT presence and
      conservation of the 5'-UTR intron in cells that have undergone EMT or in human
      tumors with low E-cadherin expression. Therefore, the results presented in this
      article reveal the existence of a NAT capable of activating Zeb2 expression,
      explain the mechanism involved in this activation, and demonstrate that this NAT
      regulates E-cadherin expression.

PMID- 18347096
TI  - Cooperation between the Hic1 and Ptch1 tumor suppressors in medulloblastoma.
AB  - Medulloblastoma is an embryonal tumor thought to arise from the granule cell
      precursors (GCPs) of the cerebellum. PATCHED (PTCH), an inhibitor of Hedgehog
      signaling, is the best-characterized tumor suppressor in medulloblastoma.
      However, <20% of medulloblastomas have mutations in PTCH. In the search for other
      tumor suppressors, interest has focused on the deletion events at the 17p13.3
      locus, the most common genetic defect in medulloblastoma. This chromosomal region
      contains HYPERMETHYLATED IN CANCER 1 (HIC1), a transcriptional repressor that is
      a frequent target of epigenetic gene silencing in medulloblastoma. Here we use a
      mouse model of Ptch1 heterozygosity to reveal a critical tumor suppressor
      function for Hic1 in medulloblastoma. When compared with Ptch1 heterozygous
      mutants, compound Ptch1/Hic1 heterozygotes display a fourfold increased incidence
      of medulloblastoma. We show that Hic1 is a direct transcriptional repressor of
      Atonal Homolog 1 (Atoh1), a proneural transcription factor essential for
      cerebellar development, and show that ATOH1 expression is required for human
      medulloblastoma cell growth in vitro. Given that Atoh1 is also a putative target
      of Hh signaling, we conclude that the Hic1 and Ptch1 tumor suppressors cooperate
      to silence Atoh1 expression during a critical phase in GCP differentiation in
      which malignant transformation may lead to medulloblastoma.

PMID- 18347097
TI  - Hed1 regulates Rad51-mediated recombination via a novel mechanism.
AB  - Two RecA orthologs, Rad51 and Dmc1, mediate homologous recombination in meiotic
      cells. During budding yeast meiosis, Hed1 coordinates the actions of Rad51 and
      Dmc1 by down-regulating Rad51 activity. It is thought that Hed1-dependent
      attenuation of Rad51 facilitates formation of crossovers that are necessary for
      the correct segregation of chromosomes at the first meiotic division. We purified
      Hed1 in order to elucidate its mechanism of action. Hed1 binds Rad51 with high
      affinity and specificity. We show that Hed1 does not adversely affect assembly of
      the Rad51 presynaptic filament, but it specifically prohibits interaction of
      Rad51 with Rad54, a Swi2/Snf2-like factor that is indispensable for Rad51
      mediated recombination. In congruence with the biochemical results, Hed1 prevents
      the recruitment of Rad54 to a site-specific DNA double-strand break in vivo but
      has no effect on the recruitment of Rad51. These findings shed light on the
      function of Hed1 and, importantly, unveil a novel mechanism for the regulation of
      homologous recombination.

PMID- 18347098
TI  - Coupling meiotic chromosome axis integrity to recombination.
AB  - During meiosis, DNA events of recombination occur in direct physical association
      with underlying chromosome axes. Meiotic cohesin Rec8 and cohesin-associated
      Spo76/Pds5 are prominent axis components. Two observations indicate that
      recombination complexes can direct the local destabilization of underlying
      chromosome axes. First, in the absence of Rec8, Spo76/Pds5 is lost locally at
      sites of late-persisting Msh4 foci, with a concomitant tendency for loosening of
      intersister and interhomolog connectedness at the affected sites. This loss is
      dependent on initiation of recombination. Second, in wild-type prophase, local
      separation of sister axes is seen at sites of synaptonemal complex-associated
      recombination nodules. Additional findings reveal that Rec8 localizes to both
      axis and bulk chromatin and is required for chromatin compactness. Further, Rec8
      is essential for maintenance of sister cohesion, along arms and centromeres,
      during the pachytene-to-diplotene transition, revealing an intrinsic tendency for
      destabilization of sister cohesion during this period. This finding shows how the
      loss of sister connectedness, in arm and/or centric regions, could lead to the
      segregation defects that are seen in the human "maternal age effect" and how Rec8
      could be a target of that effect. Finally, Rec8 plays related, but synergistic
      roles with Spo76/Pds5, indicating auxiliary roles for meiotic and mitotic
      cohesion-associated components.

PMID- 18347099
TI  - Auxin influx carriers stabilize phyllotactic patterning.
AB  - One of the most striking features of plant architecture is the regular
      arrangement of leaves and flowers around the stem, known as phyllotaxis. Peaks in
      concentration of the plant hormone auxin, generated by the polar localization of
      the PIN1 auxin efflux carrier, provide the instructive signal for primordium
      initiation. This mechanism generates the spacing between neighboring primordia,
      which results in regular phyllotaxis. Studies of the role of auxin transport in
      phyllotactic patterning have focused on PIN1-mediated efflux. Recent computer
      simulations indicate an additional role for transporter-mediated auxin uptake.
      Mutations in the AUX1 auxin influx carrier have not, however, been reported to
      cause an aerial phenotype. Here, we study the role of AUX1 and its paralogs LAX1,
      LAX2, and LAX3. Analysis of the quadruple mutant reveals irregular divergence
      angles between successive primordia. A highly unusual aspect of the phenotype is
      the occurrence of clusters of primordia, in violation of classical theory. At the
      molecular level, the sharp peaks in auxin levels and coordinated PIN polarization
      are reduced or lost. In addition, the increased penetrance of the phenotype under
      short-day conditions suggests that the AUX LAX transporters act to buffer the PIN
      mediated patterning mechanism against environmental or developmental influences.

PMID- 18347100
TI  - The insulator factor CTCF controls MHC class II gene expression and is required
      for the formation of long-distance chromatin interactions.
AB  - Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9,
      an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to
      diminish expression of these genes. The mechanism involved interactions between
      CTCF and class II transactivator (CIITA), the master regulator of major
      histocompatibility complex class II (MHC-II) gene expression, and the formation
      of long-distance chromatin loops between XL9 and the proximal promoter regions of
      these MHC-II genes. The interactions were inducible and dependent on the activity
      of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations
      show that both genes can be expressed simultaneously from the same chromosome.
      Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci
      can interact simultaneously with XL9, and describe a new regulatory mechanism for
      these MHC-II genes involving the alteration of the general chromatin conformation
      of the region and their regulation by CTCF.

PMID- 18347101
TI  - Polyomavirus BK with rearranged noncoding control region emerge in vivo in renal
      transplant patients and increase viral replication and cytopathology.
AB  - Immunosuppression is required for BK viremia and polyomavirus BK-associated
      nephropathy (PVAN) in kidney transplants (KTs), but the role of viral
      determinants is unclear. We examined BKV noncoding control regions (NCCR), which
      coordinate viral gene expression and replication. In 286 day-matched plasma and
      urine samples from 129 KT patients with BKV viremia, including 70 with PVAN, the
      majority of viruses contained archetypal (ww-) NCCRs. However, rearranged (rr-)
      NCCRs were more frequent in plasma than in urine samples (22 vs. 4%; P < 0.001),
      and were associated with 20-fold higher plasma BKV loads (2.0 x 10(4)/ml vs. 4.4
      x 10(5)/ml; P < 0.001). Emergence of rr-NCCR in plasma correlated with duration
      and peak BKV load (R(2) = 0.64; P < 0.001). This was confirmed in a prospective
      cohort of 733 plasma samples from 227 patients. For 39 PVAN patients with
      available biopsies, rr-NCCRs were associated with more extensive viral
      replication and inflammation. Cloning of 10 rr-NCCRs revealed diverse
      duplications or deletions in different NCCR subregions, but all were sufficient
      to increase early gene expression, replication capacity, and cytopathology of
      recombinant BKV in vitro. Thus, rr-NCCR BKV emergence in plasma is linked to
      increased replication capacity and disease in KTs.

PMID- 18347102
TI  - The Th17-ELR+ CXC chemokine pathway is essential for the development of central
      nervous system autoimmune disease.
AB  - The ELR(+) CXC chemokines CXCL1 and CXCL2 are up-regulated in the central nervous
      system (CNS) during multiple sclerosis (MS) and its animal model, experimental
      autoimmune encephalomyelitis (EAE). However, their functional significance and
      the pathways regulating their expression are largely unknown. We show that
      transfer of encephalitogenic CD4(+) Th17 cells is sufficient to induce CXCL1 and
      CXCL2 transcription in the spinal cords of naive, syngeneic recipients. Blockade
      or genetic silencing of CXCR2, a major receptor for these chemokines in mice,
      abrogates blood-brain barrier (BBB) breakdown, CNS infiltration by leukocytes,
      and the development of clinical deficits during the presentation as well as
      relapses of EAE. Depletion of circulating polymorphonuclear leukocytes (PMN) had
      a similar therapeutic effect. Furthermore, injection of CXCR2(+) PMN into CXCR2(
      /-) mice was sufficient to restore susceptibility to EAE. Our findings reveal
      that a Th17-ELR(+) CXC chemokine pathway is critical for granulocyte
      mobilization, BBB compromise, and the clinical manifestation of autoimmune
      demyelination in myelin peptide-sensitized mice, and suggest new therapeutic
      targets for diseases such as MS.

PMID- 18347103
TI  - The role of CTCF in regulating nuclear organization.
AB  - The spatial organization of the genome is thought to play an important part in
      the coordination of gene regulation. New techniques have been used to identify
      specific long-range interactions between distal DNA sequences, revealing an ever
      increasing complexity to nuclear organization. CCCTC-binding factor (CTCF) is a
      versatile zinc finger protein with diverse regulatory functions. New data now
      help define how CTCF mediates both long-range intrachromosomal and
      interchromosomal interactions, and highlight CTCF as an important factor in
      determining the three-dimensional structure of the genome.

PMID- 18347104
TI  - Michael T. McManus: Interrupting biology [interview by Hema Bashyam].

PMID- 18347105
TI  - Detection of methyltransferases conferring high-level resistance to
      aminoglycosides in enterobacteriaceae from Europe, North America, and Latin
      America.
AB  - The alteration of ribosomal targets by recently described 16S rRNA
      methyltransferases confers resistance to most aminoglycosides, including
      arbekacin. Enterobacteriaceae and nonfermentative bacilli acquired through global
      surveillance programs were screened for the presence of these enzymes on the
      basis of phenotypes that were resistant to nine tested aminoglycosides.
      Subsequent molecular studies determined that 20 of 21 (95.2%) methyltransferase
      positive isolates consisted of novel species records or geographic occurrences
      (North America [armA and rmtB], Latin America [rmtD], and Europe [armA]; rmtA,
      rmtC, and npmA were not detected). The global emergence of high-level
      aminoglycoside resistance has become a rapidly changing event requiring careful
      monitoring.

PMID- 18347106
TI  - Inhibition of hepatitis C virus (HCV) RNA polymerase by DNA aptamers: mechanism
      of inhibition of in vitro RNA synthesis and effect on HCV-infected cells.
AB  - We describe here the further characterization of two DNA aptamers that
      specifically bind to hepatitis C virus (HCV) RNA polymerase (NS5B) and inhibit
      its polymerase activity in vitro. Although they were obtained from the same
      selection procedure and contain an 11-nucleotide consensus sequence, our results
      indicate that aptamers 27v and 127v use different mechanisms to inhibit HCV
      polymerase. While aptamer 27v was able to compete with the RNA template for
      binding to the enzyme and blocked both the initiation and the elongation of RNA
      synthesis, aptamer 127v competed poorly and exclusively inhibited initiation and
      postinitiation events. These results illustrate the power of the selective
      evolution of ligands by exponential enrichment in vitro selection procedure
      approach to select specific short DNA aptamers able to inhibit HCV NS5B by
      different mechanisms. We also determined that, in addition to an in vitro
      inhibitory effect on RNA synthesis, aptamer 27v was able to interfere with the
      multiplication of HCV JFH1 in Huh7 cells. The efficient cellular entry of these
      short DNAs and the inhibitory effect observed on human cells infected with HCV
      indicate that aptamers are useful tools for the study of HCV RNA synthesis, and
      their use should become a very attractive and alternative approach to therapy for
      HCV infection.

PMID- 18347107
TI  - A morpholino oligomer targeting highly conserved internal ribosome entry site
      sequence is able to inhibit multiple species of picornavirus.
AB  - Members of the genera Enterovirus and Rhinovirus (family Picornaviridae) cause a
      wide range of human diseases. An established vaccine is available only for
      poliovirus, and no effective therapy is available for the treatment of infections
      caused by any pathogenic picornavirus. Peptide-conjugated phosphorodiamidate
      morpholino oligomers (PPMO) are single-stranded DNA-like antisense agents that
      readily enter cells. A panel of PPMO was tested for their antiviral activities
      against various picornaviruses. PPMO targeting conserved internal ribosome entry
      site (IRES) sequence were highly active against human rhinovirus type 14,
      coxsackievirus type B2, and poliovirus type 1 (PV1), reducing PV1 titers by up to
      6 log(10) in cell cultures. Comparative sequence analysis led us to design a PPMO
      (EnteroX) targeting 22 nucleotides of IRES sequence that are perfectly conserved
      across greater than 99% of all human enteroviruses and rhinoviruses. EnteroX
      reduced PV1 replication in cell culture to an extent similar to that of other
      IRES-specific PPMO. Resistant PV1 arose in cell cultures after 12 passages in the
      presence of EnteroX and were found to have two mutations within the EnteroX
      target sequence. Nevertheless, cPVR transgenic mice treated once daily by
      intraperitoneal (i.p.) injection with EnteroX before and/or after i.p. infection
      with 3 x 10(8) PFU (three times the 50% lethal dose) of PV1 had an approximately
      80% higher rate of survival than the controls. The viral titer in tissues taken
      at day 5 postinfection showed that animals in the EnteroX-treated group averaged
      over 3, 4, and 5 log(10) less virus in the small intestine, spinal cord, and
      brain, respectively, than the amount in the control animals. These results
      suggest that EnteroX may have broad therapeutic potential against entero- and
      rhinoviruses.

PMID- 18347108
TI  - Multiclonal outbreak of Klebsiella pneumoniae producing extended-spectrum beta
      lactamase CTX-M-2 and novel variant CTX-M-59 in a neonatal intensive care unit in
      Brazil.
AB  - An outbreak of cephalosporin-resistant Klebsiella pneumoniae occurred in a
      neonatal intensive care unit in Sao Paulo, Brazil. Of the 10 pulsotypes
      identified during the outbreak and follow-up periods, nine produced CTX-M-2 or
      its new variant CTX-M-59 and one produced SHV-5. bla(CTX-M-2/59) genes were
      located on closely related plasmids that were transferable.

PMID- 18347109
TI  - Efficacy of gamma interferon and specific antibody for treatment of
      microsporidiosis caused by Encephalitozoon cuniculi in SCID mice.
AB  - Microsporidia are eukaryotic, obligate, intracellular protists that are emerging
      pathogens in immunocompromised hosts, including AIDS patients and organ
      transplant recipients. The efficacy of gamma interferon (IFN-gamma) for the
      treatment of microsporidiosis caused by Encephalitozoon cuniculi was studied by
      means of adoptive transfer and IFN-gamma administration in SCID mice. While the
      adoptive transfer of CD4(+) T cells from immunocompetent mice prolonged survival
      of SCID mice infected perorally with E. cuniculi, survival was not improved by
      adoptive transfer of CD4(+) T lymphocytes from IFN-gamma-deficient mice. The
      protective effect of IFN-gamma was confirmed in cytokine therapy experiments in
      which SCID mice receiving IFN-gamma survived significantly longer than mice
      receiving mock injections. The administration of serum containing specific
      antibodies against E. cuniculi was found to prolong the survival of concurrently
      IFN-gamma-treated SCID mice. The data presented in this study suggest that IFN
      gamma is potentially useful as a cytokine therapy for microsporidiosis,
      especially in CD4(+) T-cell-deficient patients.

PMID- 18347110
TI  - Bovicin HC5, a lantibiotic produced by Streptococcus bovis HC5, catalyzes the
      efflux of intracellular potassium but not ATP.
AB  - Bovicin HC5, a broad-spectrum lantibiotic produced by Streptococcus bovis HC5,
      catalyzed the efflux of intracellular potassium from Streptococcus bovis JB1, a
      sensitive strain. The level of ATP also decreased, but this decline appeared to
      be caused by the activity of the F(1)F(0) ATPase rather than efflux per se.

PMID- 18347111
TI  - Chlamydia pneumoniae growth inhibition in cells by the steroid receptor
      antagonist RU486 (mifepristone).
AB  - Since steroids are powerful anti-inflammatory agents and increase susceptibility
      to a variety of infections, including Chlamydia (Chlamydophila) pneumoniae
      respiratory tract infections, the effect of the steroid receptor antagonist RU486
      (mifepristone) on C. pneumoniae growth in epithelial HEp-2 cells was examined.
      Treatment of HEp-2 cells with RU486 significantly inhibited the growth of C.
      pneumoniae in a dose-dependent manner. Electron microscopic studies also revealed
      that the treatment of infected cells with RU486 resulted in a marked destruction
      of infecting organisms. The addition of the host cell protein synthesis inhibitor
      cycloheximide to the infected cells did not alter the inhibition of C. pneumoniae
      growth by RU486. Pretreatment of C. pneumoniae organisms with RU486 before
      addition to culture also did not result in any modulation of bacterial growth in
      the cells. However, the binding of RU486 to C. pneumoniae organisms in cells at
      24 h after infection was demonstrated by immune electron microscopy with anti
      RU486 antibody. Incubation of cells with anti-RU486 antibody completely
      diminished the inhibition of C. pneumoniae growth by RU486. These results
      indicate that RU486 may directly bind to the bacteria within cells and cause the
      destruction of C. pneumoniae. This novel mode of regulation of C. pneumoniae
      growth in cells by RU486 might provide a new approach to understanding
      complicated aspects of C. pneumoniae infection.

PMID- 18347112
TI  - Susceptibility testing of anidulafungin and voriconazole alone and in combination
      against conidia and hyphae of Aspergillus spp. under hypoxic conditions.
AB  - MICs and fractional inhibitory concentrations were evaluated for anidulafungin
      and voriconazole alone and in combination against conidia and hyphae under
      hypoxic (1% oxygen-5% CO(2)-94% nitrogen) conditions against 31 Aspergillus
      isolates. Anidulafungin exhibited excellent activity against conidia and hyphae
      of Aspergillus spp. The visual reading of the MIC for anidulafungin was optimal
      under hypoxic conditions.

PMID- 18347113
TI  - Comparison of the efficacies of oral beta-lactams in selection of Haemophilus
      influenzae transformants with mutated ftsI genes.
AB  - Horizontal transfer of the mutated ftsI gene from beta-lactamase-nonproducing
      ampicillin-resistant (BLNAR) Haemophilus influenzae to a susceptible strain was
      examined in vitro under selection with nine oral beta-lactams (ampicillin,
      amoxicillin, cefprozil, cefuroxime, cefpodoxime, cefdinir, cefcapene, cefditoren,
      and tebipenem). Compared to the penicillins and the carbapenem, the
      cephalosporins showed a wide selection window for the genetic transfer.

PMID- 18347114
TI  - Biological activities of novel gyrase inhibitors of the aminocoumarin class.
AB  - Thirty-one aminocoumarin antibiotics derived from mutasynthesis experiments were
      investigated for their biological activities. Their inhibitory activities toward
      Escherichia coli DNA gyrase were determined in two different in vitro assays: an
      ATPase assay and a DNA supercoiling assay. The assays gave a similar rank order
      of the activities of the compounds tested, although the absolute 50% inhibitory
      concentrations (IC(50)s) obtained in each assay were different. To confirm that
      the compounds also acted as gyrase inhibitors in vivo, reporter gene assays were
      carried out with E. coli by using gyrA and sulA promoter fusions with the
      luxCDABE operon. A strong induction of both promoters was observed for those
      compounds that showed gyrase inhibitory activity in the biochemical assays.
      Compounds carrying analogs of the prenylated benzoyl moiety (ring A) of
      clorobiocin that were structurally very different showed high levels of activity
      both in the biochemical assay and in the reporter gene assay, indicating that the
      structure of this moiety can be varied considerably without a loss of affinity
      for bacterial gyrase. The experimentally determined IC(50)s were compared to the
      binding energies calculated in silico, which indicated that a shift of the
      pyrrole carboxylic acid moiety from the O-3'' to the O-2'' position of the
      deoxysugar moiety has a significant impact on the binding mode of the compounds.
      The aminocoumarin compounds were also investigated for their MICs against
      different bacterial pathogens. Several compounds showed high levels of activity
      against staphylococci, including a methicillin-resistant Staphylococcus aureus
      strain. However, they showed only poor activities against gram-negative strains.

PMID- 18347115
TI  - A comparison of different assessment techniques for measuring foot and ankle
      volume in healthy adults.
AB  - BACKGROUND: Foot and ankle volume may be an important measurement for conditions
      such as lower-extremity trauma or pathologic abnormalities. Water volumetry,
      often used for this measure, is accurate but not always convenient. We used
      figure-of-eight tape measurement, prism approximation, foot size measurement
      (Brannock device), and optoelectric measurement (Perometer) with the standard of
      water volumetry to compare foot and ankle volumes. METHODS: All five techniques
      were used to measure both the feet and ankles of ten asymptomatic men and women.
      Reliability was determined by repeating several trials, and validity was
      determined by comparing all of the techniques with water volumetry (the
      established standard). Regression equations were found that related each
      technique to water volumetry. RESULTS: All of the techniques were reliable
      (intraclass correlation coefficient[3,1] = 0.96-0.99). The figure-of-eight
      technique showed the highest agreement with water volumetry (R(2) = 0.96), and
      the prism method, the lowest (R(2) = 0.73). CONCLUSIONS: Although any of these
      techniques should be acceptable for monitoring foot and ankle volume in normal
      limbs, the figure-of-eight method comes closest to reproducing the results of
      water volumetry. We believe that this technique would also be best in the
      presence of foot deformities, but this remains to be studied.

PMID- 18347116
TI  - Wound complications from surgeries pertaining to the Achilles tendon: an analysis
      of 219 surgeries.
AB  - BACKGROUND: A retrospective review of one surgeon's practice was conducted to
      assess the prevalence of wound complications associated with acute and chronic
      rupture repair, peritenolysis, tenodesis, debridement, retrocalcaneal
      exostectomy/bursectomy, and management of calcific tendinopathy of the Achilles
      tendon. METHODS: We evaluated the incidence of infection and other wound
      complications, such as suture reactions, scar revision, hematoma, incisional
      neuromas, and granuloma formation. RESULTS: A total of 219 surgical cases were
      available for review (140 males and 70 females; mean +/- SD age at the time of
      surgery, 46.5 +/- 12.6 years; age range, 16-75 years). Seven patients experienced
      a wound infection, three had keloid formation, six had suture granulomas, and six
      had suture abscesses, for a total complication rate of 10.0%. Six patients had
      more than one complication; therefore, the percentage of patients with
      complications was 7.3%. There were no hematomas. Seven patients had additional
      surgery after their wound complications; some had simple granuloma excision, and
      one necessitated a flap. Patients with risk factors such as diabetes mellitus,
      smoking, and rheumatoid arthritis necessitating corticosteroid therapy were more
      likely to have a wound complication (Fisher exact test, P = .03). CONCLUSIONS:
      Complications with Achilles tendon surgery may be unavoidable. Suture granulomas
      may appear in a delayed manner. Absorbable and nonabsorbable sutures can be
      implicated.

PMID- 18347117
TI  - Arch height index measurement system: establishment of reliability and normative
      values.
AB  - BACKGROUND: The purposes of this study were 1) to determine the intrarater and
      interrater reliability of the arch height index measurement system device, 2) to
      establish population normative values for the arch height index in recreational
      runners, and 3) to compare arch height index values between the right and left
      feet and between genders. METHODS: Eleven subjects were used to establish
      intrarater and interrater reliability of the arch height index measurement
      system. This system was then used to measure the arch height index of 100
      recreational runners. RESULTS: Measurements taken with the arch height index
      measurement system device exhibited high intrarater and interrater reliability.
      The mean +/- SD arch height index of the recreational runners was 0.340 +/-
      0.030. Men had larger feet than women, but the arch height index between genders
      was similar. CONCLUSIONS: The arch height index measurement system device is
      reliable to use between testers while simplifying the measurement procedure for
      recording the arch height index. The arch height index may be helpful in
      identifying potential structural factors that predispose individuals to lower
      extremity injuries.

PMID- 18347118
TI  - Etiologic factors in the development of medial tibial stress syndrome: a review
      of the literature.
AB  - BACKGROUND: Medial tibial stress syndrome is a type of exercise-induced leg pain
      that is common in recreational and competitive athletes. Although various studies
      have attempted to find the exact pathogenesis of this common condition, it
      remains unknown. METHODS: Various theories in literature from 1976 to 2006 were
      reviewed using key words. RESULTS: Until recently, inflammation of the periosteum
      due to excessive traction was thought to be the most likely cause of medial
      tibial stress syndrome. This periostitis has been hypothesized by some authors to
      be caused by the tearing away of the muscle fibers at the muscle-bone interface,
      although there are several suggestions as to which, if any, muscle is
      responsible. CONCLUSIONS: Recent studies have supported the view that medial
      tibial stress syndrome is not an inflammatory process of the periosteum but
      instead a stress reaction of bone that has become painful.

PMID- 18347119
TI  - Effect of foot morphology on center-of-pressure excursion during barefoot
      walking.
AB  - BACKGROUND: The path of the center of pressure during walking varies among
      individuals by deviating to a greater or lesser extent toward the medial or
      lateral border of the foot. It is unclear whether this variance is systematic and
      is affected by foot posture. The aim of this study was to explore the
      relationship between foot morphology and center-of-pressure excursion during
      barefoot walking. METHODS: Pressure data were collected from 83 participants
      whose foot type had been classified as supinated, normal, or pronated according
      to the Foot Posture Index. Three center-of-pressure variables were analyzed:
      medial excursion area, lateral excursion area, and total excursion area. RESULTS:
      Across the spectrum of foot types, we found that the more supinated a
      participant's foot posture, the larger the area of lateral center-of-pressure
      excursion, and, conversely, the more pronated the foot posture, the smaller the
      area of lateral center-of-pressure excursion. Furthermore, the supinated foot
      type had a relatively larger center-of-pressure total excursion area, and the
      pronated foot type had a relatively smaller center-of-pressure total excursion
      area. CONCLUSIONS: These results indicate the importance of assessing foot
      posture when measuring center of pressure and may help explain regional
      differences in pain and injury location among foot types.

PMID- 18347120
TI  - Efficacy of wedge resection with phenolization in the treatment of ingrowing
      toenails.
AB  - BACKGROUND: Ingrowing toenail is a common condition treated by general surgeons.
      Our aim was to analyze the effectiveness of wedge resection with phenolization in
      the surgical treatment of ingrowing toenails. METHODS: We retrospectively audited
      100 patients who underwent wedge resection with phenolization for the treatment
      of ingrowing toenail between January 2000 and June 2004 by a single surgeon. We
      reviewed all charts and attempted to contact all patients for a telephone
      interview to assess patient satisfaction. Outcome measures were: 1) recurrence
      rate, 2) duration of analgesic use, 3) postoperative complications including
      wound infection, 4) time to return to normal activities, and 5) satisfaction with
      the procedure. RESULTS: A total of 168 wedge resection with phenolization
      procedures were performed on 100 patients. There was only one recurrence (0.6%).
      Two patients (2%) had wound infection and were treated with oral antibiotics. The
      average time for a single wedge resection with phenolization procedure was 7.3
      minutes. The mean time to return to normal activities was 2.1 weeks. The patient
      response rate for the telephone interview was 60%. Most respondents (93.3%) were
      satisfied with the overall outcome. CONCLUSIONS: Wedge resection with
      phenolization is a very effective mode of therapy in the surgical treatment of
      ingrowing toenail, with a very low recurrence rate and minimal postoperative
      morbidity. Wedge resection with phenolization should be considered as a good
      alternative technique in the treatment of ingrowing toenail.

PMID- 18347121
TI  - Length of the sesamoids and their distance from the metatarsophalangeal joint
      space in feet with incipient hallux limitus.
AB  - BACKGROUND: We designed this study to verify whether the sesamoids of the first
      metatarsal head are longer than normal in feet with incipient hallux limitus, and
      whether feet with incipient hallux limitus are in a more proximal than normal
      sesamoid position. METHODS: In a sample of 183 dorsoplantar radiographs under
      weightbearing conditions (115 of normal feet and 68 of feet with slightly stiff
      hallux), measurements were made of the length of both the medial and the lateral
      sesamoids and of the distance between these bones to the distal edge of the first
      metatarsal head. These variables were compared between the normal and the hallux
      limitus feet. The relationship between these variables and the hallux
      dorsiflexion was also studied. RESULTS: We found significant differences between
      the two types of foot in the medial and lateral sesamoid lengths, but no
      significant difference in the distance between the sesamoids to the distal edge
      of the first metatarsal. A poor-to-moderate inverse correlation was found between
      hallux dorsiflexion and medial sesamoid length and between hallux dorsiflexion
      and lateral sesamoid length. CONCLUSIONS: The length of the sesamoid bones of the
      first metatarsal head could be implicated in the development of the hallux
      limitus deformity.

PMID- 18347122
TI  - The diabetic person beyond a foot ulcer: healing, recurrence, and depressive
      symptoms.
AB  - BACKGROUND: Several studies have shown a significant relationship between
      depressive symptoms and wound healing, but these studies have not assessed the
      effects of depressive symptoms on diabetic foot prognosis. We specifically
      designed our study to assess the role of depressive symptoms in healing and
      recurrence of diabetic foot ulcers. METHODS: A consecutive series of 80 type 2
      diabetic patients aged 60 years and older with foot ulcers was enrolled in a
      cohort observational study with a 6-month follow-up. Patients who healed within 6
      months of enrollment were included in a 12-month follow-up study for assessment
      of ulcer recurrence. Depressive symptoms were assessed with the geriatric
      depression scale. RESULTS: Healing was associated with a smaller ulcer area,
      shorter delay between ulcer onset and treatment, lower glycosylated hemoglobin,
      and higher ankle-brachial index. Both smoking status and Texas and Wagner scores
      also had a significant impact on healing. Patients who healed had significantly
      lower scores on the geriatric depression scale, and those with scores = 10 had a
      significantly higher risk of not healing at 6 months (relative risk, 3.57; 95%
      confidence interval, 1.05-12.2). Patients with a recurrent ulcer (59.3%) showed
      significantly higher total cholesterol levels, higher scores on the Greenfield
      index of disease severity and geriatric depression scale, and a higher prevalence
      of cerebrovascular disease. Depressive symptoms maintained a significant
      association with persistence and recurrence of ulcer even after adjustment for
      confounders. CONCLUSIONS: Depressive symptoms are associated with impaired
      healing and recurrence of ulcers in elderly type 2 diabetic patients.

PMID- 18347123
TI  - What's Your Diagnosis? Heloma Neurofibrosum.

PMID- 18347124
TI  - Use of a muscle flap and a split-thickness skin graft for a calcaneal
      osteomyelitis after an open reduction and internal fixation.
AB  - Reconstruction of bone and soft-tissue defects after an open reduction and
      internal fixation of a severely comminuted calcaneal fracture presents a
      challenge to the treating surgeon. We present a case report in which an abductor
      digiti minimi muscle flap was used to cover a complicated wound with calcaneal
      osteomyelitis and wound dehisence at the surgical incision. This muscle flap
      provides an easy, reliable, and quick method to cover open wounds at the lateral
      aspect of the foot and ankle.

PMID- 18347125
TI  - Comparison of orthotic materials on foot pain, comfort, and plantar pressure in
      the neuroischemic diabetic foot: a case report.
AB  - Foot pain and lower-limb neuroischemia in diabetes mellitus is common and can be
      debilitating and difficult to treat. We report a comparison of orthotic materials
      to manage foot pain in a 59-year-old man with type 1 diabetes mellitus,
      peripheral neuropathy, peripheral arterial disease, and a history of foot
      ulceration. We investigated a range of in-shoe foot orthoses for comfort and
      plantar pressure reduction in a cross-sectional study. The most comfortable and
      most effective pressure-reducing orthoses were subsequently evaluated for pain
      relief in a single system alternating-treatment design. After 9 weeks, foot pain
      was completely resolved with customized multidensity foot orthoses. The outcome
      of this case study suggests that customized multidensity foot orthoses may be a
      useful intervention to reduce foot pain and maintain function in the
      neuroischemic diabetic foot.

PMID- 18347126
TI  - Traumatic dislocation of the first metatarsophalangeal joint with tibial sesamoid
      fracture: a case report of a type III B dislocation.
AB  - We present a case report about traumatic dislocation of the first
      metatarsophalangeal joint and patterns of injury. We are unaware of previous
      reports in the literature describing this unusual variant.

PMID- 18347127
TI  - Charcot's arthropathy in a patient with HIV-associated neuropathy.
AB  - Charcot's arthropathy is a destructive arthritis that can occur in patients with
      peripheral neuropathies of various etiologies. This report describes a rare case
      of Charcot's arthropathy attributable to the distal sensory polyneuropathy
      associated with HIV infection. As treatments for HIV/AIDS advance and life
      expectancy increases, cases of end-organ sequelae, such as Charcot foot, may
      become more common.

PMID- 18347128
TI  - Injectable botulinum toxin as a treatment for plantar hyperhidrosis: a case
      study.
AB  - Hyperhidrosis is defined as excessive and uncontrollable sweating due to
      overactivity of the eccrine sweat glands. The first line of treatment for plantar
      hyperhidrosis consists of conservative therapies such as topical solutions (ie,
      antiperspirant applications and aluminum chloride preparations) and
      iontophoresis. When the patient has failed these standard treatments, the other
      available medical options are rather limited and not well tolerated. Botulinum
      toxin type A (Botox, Allergan Inc, Irvine, California) is a purified neurotoxin
      complex approved by the US Food and Drug Administration in 2004 for multiple
      medical conditions, including severe primary axillary hyperhidrosis that failed
      conservative topical therapies. Few recent clinical studies have suggested that
      botulinum toxin is effective in the treatment of plantar hyperhidrosis. In this
      case study, two patients received intradermal injections of botulinum toxin type
      A into the plantar aspect of both feet. A 3-month follow-up evaluated the
      efficacy of botulinum toxin type A by subjectively assessing the amount of
      residual sweating. In these two patients, botulinum toxin type A was an effective
      and safe treatment for plantar hyperhidrosis.

PMID- 18347129
TI  - Interposition arthroplasty of the first metatarsophalangeal joint with a fascia
      lata allograft.
AB  - A new technique for interposition arthroplasty of the first metatarsoplalangeal
      joint is described. It involves minimal resection of the base of the proximal
      phalanx and the use of a fascia lata allograft. The method is simple, safe, and
      easily reproducible. In selected cases it can offer restoration of pain-free
      motion in a nonsalvable joint.

PMID- 18347130
TI  - Negative-pressure wound therapy and diabetic foot amputations: a retrospective
      study of Payer Claims Data.

PMID- 18347132
TI  - Turning the gene tap off; implications of regulating gene expression for cancer
      therapeutics.
AB  - Cancer poses a tremendous therapeutic challenge worldwide, highlighting the
      critical need for developing novel therapeutics. A promising cancer treatment
      modality is gene therapy, which is a form of molecular medicine designed to
      introduce into target cells genetic material with therapeutic intent. Anticancer
      gene therapy strategies currently used in preclinical models, and in some cases
      in the clinic, include proapoptotic genes, oncolytic/replicative vectors,
      conditional cytotoxic approaches, inhibition of angiogenesis, inhibition of
      growth factor signaling, inactivation of oncogenes, inhibition of tumor invasion
      and stimulation of the immune system. The translation of these novel therapeutic
      modalities from the preclinical setting to the clinic has been driven by
      encouraging preclinical efficacy data and advances in gene delivery technologies.
      One area of intense research involves the ability to accurately regulate the
      levels of therapeutic gene expression to achieve enhanced efficacy and provide
      the capability to switch gene expression off completely if adverse side effects
      should arise. This feature could also be implemented to switch gene expression
      off when a successful therapeutic outcome ensues. Here, we will review recent
      developments related to the engineering of transcriptional switches within gene
      delivery systems, which could be implemented in clinical gene therapy
      applications directed at the treatment of cancer.

PMID- 18347133
TI  - Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor
      cell death and antitumor activity.
AB  - M30 and M65 are ELISAs that detect different circulating forms of cytokeratin 18.
      Using the aurora kinase inhibitor AZD1152 and the SW620 human colon cancer
      xenograft, experiments were conducted to qualify preclinically both assays as
      serologic biomarkers of cell death. Using two different apoptotic markers, the
      kinetics of cell death induced by AZD1152 was first characterized in vitro in
      three different cell lines and shown to peak 5 to 7 days after drug addition.
      Treatment of non-tumor-bearing rats with AZD1152 (25 mg/kg) produced no
      alterations in circulating baseline values of M30 and M65 antigens. In treated,
      tumor-bearing animals, M30 detected a 2- to 3-fold (P < 0.05) increase in plasma
      antigen levels by day 5 compared with controls. This correlated to a 3-fold
      increase in the number of apoptotic cells detected on day 5 in SW620 xenografts
      using immunohistochemistry. By contrast, M65 did not detect a drug-induced
      increase in circulating antigen levels at day 5. However, M65 plasma levels
      correlated to changes in tumor growth in control animals (r(2) = 0.93; P < 0.01)
      and also followed the magnitude of the temporal effect of AZD1152 on tumor
      growth. An intermediate but active dose of AZD1152 (12.5 mg/kg) produced a less
      significant increase in M30 plasma levels at day 5. It was also confirmed that
      the plasma profiles of M30 and M65 mirrored closely those measured in whole tumor
      lysates. We conclude that M30 is a pharmacodynamic biomarker of AZD1152-induced
      apoptosis in the SW620 xenograft model, whereas M65 is a biomarker of therapeutic
      response.

PMID- 18347134
TI  - Curcumin (diferuloylmethane) alters the expression profiles of microRNAs in human
      pancreatic cancer cells.
AB  - BACKGROUND: A major challenge in cancer chemotherapy has been developing safe and
      clinically efficacious chemotherapeutic agents. With its low toxicity profile,
      curcumin (diferuloylmethane), a naturally occurring flavinoid derived from the
      rhizome of Curcuma longa, has great promise. In vitro and in vivo preclinical
      studies have shown its inhibitory anticancer, antioxidant, anti-inflammatory,
      antiproliferative, and proapoptotic activities. The multiple mechanisms of the
      antitumor effect of curcumin putatively include down-regulating the expression of
      gene products such as nuclear factor-kappaB, growth suppression, inducing
      apoptosis, and modulating various signal transduction pathways and the expression
      of many oncogenes. The mechanisms underlying the antitumor activity of curcumin
      have not, however, been completely delineated. METHODS: An oligonucleotide
      microarray chip was developed and used to profile microRNA (miRNA) expressions in
      pancreatic cells treated with curcumin. Transcripts with regulated expression
      patterns on the arrays were validated by real-time PCRs. Additionally, potential
      mRNA targets were analyzed bioinformatically and confirmed with flow cytometry
      experiments. RESULTS: Curcumin alters miRNA expression in human pancreatic cells,
      up-regulating miRNA-22 and down-regulating miRNA-199a*, as confirmed by TaqMan
      real-time PCR. Upregulation of miRNA-22 expression by curcumin or by transfection
      with miRNA-22 mimetics in the PxBC-3 pancreatic cancer cell line suppressed
      expression of its target genes SP1 transcription factor (SP1) and estrogen
      receptor 1 (ESR1), while inhibiting miRNA-22 with antisense enhanced SP1 and ESR1
      expression. CONCLUSIONS: These observations suggest that modulation of miRNA
      expression may be an important mechanism underlying the biological effects of
      curcumin.

PMID- 18347135
TI  - Dicoumarol down-regulates human PTTG1/Securin mRNA expression through inhibition
      of Hsp90.
AB  - Securin, the natural inhibitor of sister chromatid untimely separation, is a
      protooncogene overexpressed in tumors. Its protein levels correlate with
      malignancy and metastatic proneness. Dicoumarol, a long-established oral
      anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/Securin gene
      expression and provokes apoptosis through a complex trait involving both
      intrinsic and extrinsic pathways. Dicoumarol activity as an Hsp90 inhibitor is
      confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of
      in vivo heat shock luciferase activity recovery assays. Likewise, established
      Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress
      PTTG1/Securin gene expression. Also, overexpression of human Hsp90 in yeast makes
      them hypersensitive to dicoumarol. Both apoptosis and PTTG1/Securin gene
      repression exerted by dicoumarol in cancer cells are independent of three of the
      most important signaling pathways affected by Hsp90 inhibition: nuclear factor
      kappaB, p53, or Akt/protein kinase B signaling pathways. However, effects on
      PTTG1/Securin could be partially ascribed to inhibition of the
      Ras/Raf/extracellular signal-regulated kinase pathway. Overall, we show that
      expression of PTTG1/Securin gene is Hsp90 dependent and that dicoumarol is a bona
      fide Hsp90 inhibitor. These findings are important to understand the mode of
      action of Hsp90 inhibitors, mechanisms of action of dicoumarol, and Securin
      overexpression in tumors.

PMID- 18347136
TI  - Mitochondrial regulation by c-Myc and hypoxia-inducible factor-1 alpha controls
      sensitivity to econazole.
AB  - Econazole is an azole antifungal with anticancer activity that blocks Ca(2+)
      influx and stimulates endoplasmic reticulum (ER) Ca(2+) release through the
      generation of mitochondrial reactive oxygen species (ROS), resulting in sustained
      depletion of ER Ca(2+) stores, protein synthesis inhibition, and cell death. c
      Myc, a commonly activated oncogene, also promotes apoptosis in response to growth
      factor withdrawal and a variety of chemotherapeutic agents. We have investigated
      the role of c-myc in regulating sensitivity to econazole. Here, we show that c
      myc-negative cells are profoundly resistant to econazole. c-Myc-negative rat
      fibroblasts failed to generate mitochondrial ROS in response to econazole and
      consequently failed to deplete the ER of Ca(2+). HL60 cells knocked down for c
      myc expression also displayed decreased ROS generation and decreased econazole
      sensitivity. Addition of H(2)O(2) restored sensitivity to econazole in both c-myc
      negative rat fibroblasts and c-myc knocked-down HL60 cells, supporting a role for
      ROS in cell death induction. c-Myc-negative cells and HL60 cells knocked down for
      c-myc have reduced mitochondrial content compared with c-myc-positive cells. The
      hypoxia sensor, hypoxia-inducible factor-1alpha (HIF-1alpha), interacts
      antagonistically with c-myc and also regulates mitochondrial biogenesis.
      Knockdown of HIF-1alpha in c-myc-negative cells increased mitochondrial content
      restored ROS generation in response to econazole and increased sensitivity to the
      drug. Taken together, these results show that c-myc and HIF-1alpha regulate
      sensitivity to econazole by modulating the ability of the drug to generate
      mitochondrial ROS.

PMID- 18347137
TI  - A novel B-RAF inhibitor blocks interleukin-8 (IL-8) synthesis in human melanoma
      xenografts, revealing IL-8 as a potential pharmacodynamic biomarker.
AB  - B-RAF mutations have been identified in the majority of melanoma and a large
      fraction of colorectal and papillary thyroid carcinoma. Drug discovery efforts
      targeting mutated B-RAF have yielded several interesting molecules, and
      currently, three compounds are undergoing clinical evaluation. Inhibition of B
      RAF in animal models leads to a slowing of tumor growth and, in some cases, tumor
      reduction. Described within is a novel series of diaryl imidazoles with potent,
      single-digit nanomolar, anti-B-RAF activity. One compound from this series has
      been detailed here and has been shown to block B-RAF(V600E)-dependent
      extracellular signal-regulated kinase 1/2 phosphorylation in SK-MEL-28 melanoma
      cells as well as soft agar colony formation and proliferation. Importantly,
      interleukin-8 (IL-8) was identified by quantitative real-time PCR and ELISA as a
      product of the elevated mitogen-activated protein kinase signaling in these
      cells. Plasma concentrations of IL-8 in mice bearing melanoma xenografts were
      significantly reduced following exposure to B-RAF inhibitors. Taken together,
      these data suggest that IL-8 could serve as a tractable clinical biomarker.

PMID- 18347138
TI  - Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl
      4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo.
AB  - Preclinical studies have shown that nitric oxide (NO)-donating nonsteroidal anti
      inflammatory drugs possess anticancer activities. Here, we report in vitro and in
      vivo studies showing the antitumor effect of the NO-donating isoxazole derivative
      (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not
      the NO-deprived parental compound VGX-1027, significantly affected viability of
      both rodent (L929, B16, and C6) and human (U251, BT20, HeLa, and LS174) tumor
      cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or
      autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the
      viability of cisplatin-resistant B16 cells. NO scavenger hemoglobin completely
      prevented GIT-27NO-induced death, indicating that NO release mediated the
      tumoricidal effect of the compound. Increase in intracellular NO upon on the
      treatment was associated with intensified production of reactive oxygen species,
      whereas their neutralization by antioxidant N-acetylcysteine resulted in partial
      recovery of cell viability. The antitumor activity of the drug was mediated by
      the selective activation of mitogen-activated protein kinases in a cell-specific
      manner and was neutralized by their specific inhibitors. In vivo treatment with
      GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice.
      The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than
      those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT
      27NO five times higher than that found effective in the melanoma model was well
      tolerated by the mice when administered for 4 consecutive weeks. These data
      warrant additional studies to evaluate the possible translation of these findings
      to the clinical setting.

PMID- 18347139
TI  - A small-molecule inhibitor of Tcf/beta-catenin signaling down-regulates PPARgamma
      and PPARdelta activities.
AB  - Activation of the Wnt/beta-catenin signaling pathway occurs in several types of
      cancers and thus it is an attractive target for anticancer drug development. To
      identify compounds that inhibit this pathway, we screened a chemical library
      using a cell-based beta-catenin/Tcf-responsive reporter. We identified FH535, a
      compound that suppresses both Wnt/beta-catenin and peroxisome proliferator
      activated receptor (PPAR) signaling. FH535 antagonizes both PPARgamma and
      PPARdelta ligand-dependent activation and shows structural similarity to GW9662,
      a known PPARgamma antagonist. The effect of FH535 on beta-catenin/Tcf activity is
      reduced in cells carrying a deletion of the PPARdelta gene, as well as by the
      PPARgamma agonist lysophosphatidic acid. Mechanistically, FH535 inhibits
      recruitment of the coactivators beta-catenin and GRIP1 but not the corepressors
      NCoR and SMRT. Its repression of beta-catenin recruitment, in comparison with
      GW9662, is linked to FH535's unique capability to inhibit the Wnt/beta-catenin
      signaling pathway. The antiproliferation effect of the compound observed on some
      transformed colon lung and liver cell lines is suggestive of its potential
      therapeutic value in the treatment of cancer.

PMID- 18347140
TI  - p37 from Mycoplasma hyorhinis promotes cancer cell invasiveness and metastasis
      through activation of MMP-2 and followed by phosphorylation of EGFR.
AB  - High Mycoplasma infection in gastric cancer tissues suggests a possible
      association between Mycoplasma infection and tumorigenesis. By using human
      gastric cancer cells AGS and mouse melanoma cells B16F10 stably expressing p37,
      the major immunogen of Mycoplasma hyorhinis, we found that p37 enhanced cell
      motility, migration, and invasion in vitro. With experimental metastasis model in
      C57BL/6 mice, p37 adenovirus-infected B16F10 cells formed more metastasis lesions
      in the lung. Furthermore, p37 promoted the phosphorylation of epidermal growth
      factor receptor (EGFR) and extracellular signal-regulated kinase and the activity
      of matrix metalloproteinase-2 (MMP-2). Inhibitor of MMPs significantly blocked
      p37-induced EGFR but has little effect on extracellular signal-regulated kinase
      phosphorylation, whereas the p37-induced MMP-2 activation was only partially
      suppressed by inhibitor of MEK1/2 or by inhibitor of EGFR. However, all these
      inhibitors significantly reduced the p37-induced invasiveness of AGS cells. These
      results suggest that p37 may stimulate invasion by increasing the activity of MMP
      2, thereby inducing EGFR phosphorylation and contributing to tumor metastasis on
      M. hyorhinis infection. p37 and its regulated molecules could be the potential
      targets for cancer therapy.

PMID- 18347141
TI  - Recombinant cathepsin S propeptide attenuates cell invasion by inhibition of
      cathepsin L-like proteases in tumor microenvironment.
AB  - Human cathepsin L along with cathepsin S, K, and V are collectively known as
      cathepsin L-like proteases due to their high homology. The overexpression and
      aberrant activity of each of these proteases has been implicated in
      tumorigenesis. These proteases contain propeptide domains that can potently
      inhibit both their cognate protease and other proteases within the cathepsin L
      like subfamily. In this investigation, we have produced the cathepsin S
      propeptide recombinantly and have shown that it is a potent inhibitor of the
      peptidolytic, elastinolytic, and gelatinolytic activities of the cathepsin L-like
      proteases. In addition, we show that this peptide is capable of significantly
      attenuating tumor cell invasion in a panel of human cancer cell lines.
      Furthermore, fusion of an IgG Fc-domain to the COOH terminus of the propeptide
      resulted in a chimeric protein with significantly enhanced ability to block tumor
      cell invasion. This Fc fusion protein exhibited enhanced stability in cell-based
      assays in comparison with the unmodified propeptide species. This approach for
      the combined inhibition of the cathepsin L-like proteases may prove useful for
      the further study in cancer and other conditions where their aberrant activity
      has been implicated. Furthermore, this strategy for simultaneous inhibition of
      multiple cysteine cathepsins may represent the basis for novel therapeutics to
      attenuate tumorigenesis.

PMID- 18347142
TI  - Agelastatin A: a novel inhibitor of osteopontin-mediated adhesion, invasion, and
      colony formation.
AB  - Effective inhibitors of osteopontin (OPN)-mediated neoplastic transformation and
      metastasis are still lacking. (-)-Agelastatin A is a naturally occurring oroidin
      alkaloid with powerful antitumor effects that, in many cases, are superior to
      cisplatin in vitro. In this regard, past comparative assaying of the two agents
      against a range of human tumor cell lines has revealed that typically (-)
      agelastatin A is 1.5 to 16 times more potent than cisplatin at inhibiting cell
      growth, its effects being most pronounced against human bladder, skin, colon, and
      breast carcinomas. In this study, we have investigated the effects of (-)
      agelastatin A on OPN-mediated malignant transformation using mammary epithelial
      cell lines. Treatment with (-)-agelastatin A inhibited OPN protein expression and
      enhanced expression of the cellular OPN inhibitor, Tcf-4. (-)-Agelastatin A
      treatment also reduced beta-catenin protein expression and reduced anchorage
      independent growth, adhesion, and invasion in R37 OPN pBK-CMV and C9 cell lines.
      Similar effects were observed in MDA-MB-231 and MDA-MB-435s human breast cancer
      cell lines exposed to (-)-agelastatin A. Suppression of Tcf-4 by RNA interference
      (short interfering RNA) induced malignant/invasive transformation in parental
      benign Rama 37 cells; significantly, these events were reversed by treatment with
      (-)-agelastatin A. Our study reveals, for the very first time, that (-)
      agelastatin A down-regulates beta-catenin expression while simultaneously up
      regulating Tcf-4 and that these combined effects cause repression of OPN and
      inhibition of OPN-mediated malignant cell invasion, adhesion, and colony
      formation in vitro. We have also shown that (-)-agelastatin A inhibits cancer
      cell proliferation by causing cells to accumulate in the G(2) phase of cell
      cycle.

PMID- 18347143
TI  - Tumor-targeting nanodelivery enhances the anticancer activity of a novel
      quinazolinone analogue.
AB  - GMC-5-193 (GMC) is a novel anticancer small-molecule quinazolinone analogue with
      properties that include antimicrotubule activity and inherent fluorescence. The
      aim of this study was to produce and optimize a systemically administered
      liposomal formulation for tumor-targeting delivery of GMC to enhance the
      anticancer effect of this compound and evaluate its bioefficacy. GMC was
      encapsulated within a cationic liposome, which was decorated on the surface with
      an anti-transferrin receptor single-chain antibody fragment (TfRscFv) as the
      tumor-targeting moiety to form a nanoscale complex (scL/GMC). Confocal imaging of
      fluorescent GMC uptake in a human melanoma cell line, MDA-MB-435, showed higher
      cellular uptake of GMC when delivered via the liposome complex compared with free
      GMC. Delivery of GMC by the tumor-targeting liposome nanoimmunocomplex also
      resulted in a 3- to 4-fold decrease in IC(50) values in human cancer cells [DU145
      (prostate) and MDA-MB-435] compared with the effects of GMC administered as free
      GMC. In addition, the GMC nanoimmunocomplex increased the sensitivity of cancer
      cells to doxorubicin, docetaxel, or mitoxantrone by approximately 3- to 30-fold.
      In the MDA435/LCC6 athymic nude mice xenograft lung metastases model, GMC was
      specifically delivered to tumors by the nanoimmunocomplex. These data show that
      incorporation of small-molecule therapeutic GMC within the tumor-targeting
      liposome nanocomplex enhances its anticancer effect.

PMID- 18347144
TI  - Hepatocellular carcinoma cell-specific peptide ligand for targeted drug delivery.
AB  - Hepatocellular carcinoma is the fourth leading cause of cancer death worldwide.
      Novel treatment strategies derived from increased knowledge of molecular oncology
      are constantly being developed to cure this disease. Here, we used phage display
      to identify a novel peptide (SP94), which binds specifically to hepatocellular
      carcinoma cells. In vitro, the phage clone PC94 was shown to bind to
      hepatocellular carcinoma cell lines by ELISA and flow cytometry analysis. In
      vivo, PC94 homed specifically to tumor tissues but not to normal visceral organs
      in severe combined immunodeficient mice bearing human hepatocellular carcinoma
      xenografts. This homing ability could be competitively inhibited by synthetic
      peptide, SP94. Immunohistochemical staining confirmed that PC94 localized to
      tumor tissues and that it could not be detected in SP94-competed tumor tissues.
      In addition, PC94 recognized the tumor tissue but not nontumor tissue in surgical
      specimens from hepatocellular carcinoma patients, with a positive rate of 61.3%
      (19 of 31). With the conjugation of SP94 and liposomal doxorubicin, the targeted
      drug delivery system enhanced the therapeutic efficacy against hepatocellular
      carcinoma xenografts through enhanced tumor apoptosis and decreased tumor
      angiogenesis. Our results indicate that SP94 has the potential to improve the
      systemic treatment of patients with advanced hepatocellular carcinoma.

PMID- 18347145
TI  - Dual inhibition of VEGFR and EGFR signaling reduces the incidence and size of
      intestinal adenomas in Apc(Min/+) mice.
AB  - Both the epidermal growth factor (EGF) and the vascular endothelial growth factor
      (VEGF) pathways are associated with intestinal cancer, and therapeutic approaches
      targeting either EGF receptor (EGFR) or VEGF receptor (VEGFR) signaling have
      recently been approved for patients with advanced colorectal cancer. The
      Apc(Min/+) mouse is a well-characterized in vivo model of intestinal
      tumorigenesis, and animals with this genetic mutation develop macroscopically
      detectable adenomas from approximately 6 weeks of age. Previous work in the
      Apc(Min/+) mouse has shown that therapeutic approaches targeting either VEGFR or
      EGFR signaling affect predominantly the size or number of adenomas, respectively.
      In this study, we have assessed the effect of inhibiting both these key pathways
      simultaneously using ZD6474 (Vandetanib, ZACTIMA), a selective inhibitor of VEGFR
      and EGFR tyrosine kinases. To assess the effects of ZD6474 on early- and later
      stage disease, treatment was initiated in 6- and 10-week-old Apc(Min/+) mice for
      28 days. ZD6474 markedly reduced both the number and the size of polyps when
      administered at either an early or a later stage of polyp development. This
      reduction in both adenoma number and size resulted in a total reduction in tumor
      burden in the small intestine of nearly 75% in both studies (P < 0.01). The
      current data build on the concept that EGFR-dependent tumor cell proliferation
      and VEGF/VEGFR2-dependent angiogenesis and survival are distinct key mechanisms
      in polyp development. Pharmacologic inhibition of both signaling pathways has
      significant antitumor effects at both early and late stages of polyp development.
      Therefore, targeting both VEGFR- and EGFR-dependent signaling may be a beneficial
      strategy in early intestinal cancer.

PMID- 18347146
TI  - Synergistic antitumor effect of S-1 and the epidermal growth factor receptor
      inhibitor gefitinib in non-small cell lung cancer cell lines: role of gefitinib
      induced down-regulation of thymidylate synthase.
AB  - Somatic mutations in the epidermal growth factor receptor (EGFR) gene are
      associated with the therapeutic response to EGFR tyrosine kinase inhibitors (TKI)
      in patients with advanced non-small cell lung cancer (NSCLC). The response rate
      to these drugs remains low, however, in NSCLC patients with wild-type EGFR
      alleles. Combination therapies with EGFR-TKIs and cytotoxic agents are considered
      a therapeutic option for patients with NSCLC expressing wild-type EGFR. We
      investigated the antiproliferative effect of the combination of the oral
      fluorouracil S-1 and the EGFR-TKI gefitinib in NSCLC cells of differing EGFR
      status. The combination of 5-fluorouracil and gefitinib showed a synergistic
      antiproliferative effect in vitro in all NSCLC cell lines tested. Combination
      chemotherapy with S-1 and gefitinib in vivo also had a synergistic antitumor
      effect on NSCLC xenografts regardless of the absence or presence of EGFR
      mutations. Gefitinib inhibited the expression of the transcription factor E2F-1,
      resulting in the down-regulation of thymidylate synthase at the mRNA and protein
      levels. These observations suggest that gefitinib-induced down-regulation of
      thymidylate synthase is responsible, at least in part, for the synergistic
      antitumor effect of combined treatment with S-1 and gefitinib and provide a basis
      for clinical evaluation of combination chemotherapy with S-1 and EGFR-TKIs in
      patients with solid tumors.

PMID- 18347147
TI  - Combined lapatinib and cetuximab enhance cytotoxicity against gefitinib-resistant
      lung cancer cells.
AB  - Although non-small cell lung cancer (NSCLC) cells with somatic mutations in their
      epidermal growth factor receptors (EGFR) initially show a dramatic response to
      tyrosine kinase inhibitor (TKI), these cells eventually develop resistance to
      TKI. This resistance may be caused by a secondary T790M mutation in the EGFR
      tyrosine kinase, which leads to the substitution of methionine for threonine in
      790. In this study, we show that a combination of lapatinib and cetuximab
      overcomes gefitinib resistance in NSCLC with the T790M mutation. We observed that
      T790M lung cancer cells were resistant to gefitinib, and Stat3 was persistently
      activated in the resistant cells. A reversible EGFR and HER2 TKI, lapatinib,
      decreased Stat3 activation by blocking heterodimerization of EGFR and HER2, which
      led to a modest increase in the inhibitory effect on gefitinib-resistant T790M
      cells. In addition to lapatinib, the anti-EGFR antibody, cetuximab, induced down
      regulation of EGFR and apoptotic cell death in T790M cells. Finally, combined
      lapatinib and cetuximab treatment resulted in significantly enhanced cytotoxicity
      against gefitinib-resistant T790M cells in vitro and in vivo. Taken together,
      these data suggest that treatment with a combination of lapatinib and cetuximab,
      which induces dimeric dissociation and EGFR down-regulation, appears to be an
      effective strategy for treatment of patients with EGFR TKI-resistant NSCLC.

PMID- 18347148
TI  - Transient exposure of carcinoma cells to RAS/MEK inhibitors and UCN-01 causes
      cell death in vitro and in vivo.
AB  - The present studies were initiated to determine in greater molecular detail how
      MEK1/2 inhibitors [PD184352 and AZD6244 (ARRY-142886)] interact with UCN-01 (7
      hydroxystaurosporine) to kill mammary carcinoma cells in vitro and radiosensitize
      mammary tumors in vitro and in vivo and whether farnesyl transferase inhibitors
      interact with UCN-01 to kill mammary carcinoma cells in vitro and in vivo.
      Expression of constitutively activated MEK1 EE or molecular suppression of JNK
      and p38 pathway signaling blocked MEK1/2 inhibitor and UCN-01 lethality, effects
      dependent on the expression of BAX, BAK, and, to a lesser extent, BIM and BID. In
      vitro colony formation studies showed that UCN-01 interacted synergistically with
      the MEK1/2 inhibitors PD184352 or AZD6244 and the farnesyl transferase inhibitors
      FTI277 and R115,777 to kill human mammary carcinoma cells. Athymic mice carrying
      approximately 100 mm(3) MDA-MB-231 cell tumors were subjected to a 2-day exposure
      of either vehicle, R115,777 (100 mg/kg), the MEK1/2 inhibitor PD184352 (25
      mg/kg), UCN-01 (0.2 mg/kg), or either of the drugs in combination with UCN-01.
      Transient exposure of tumors to R115,777, PD184352, or UCN-01 did not
      significantly alter tumor growth rate or the mean tumor volume in vivo
      approximately 15 to 30 days after drug administration. In contrast, combined
      treatment with R115,777 and UCN-01 or with PD184352 and UCN-01 significantly
      reduced tumor growth. Tumor cells isolated after combined drug exposure exhibited
      a significantly greater reduction in plating efficiency using ex vivo colony
      formation assays than tumor cells that were exposed to either drug individually.
      Irradiation of mammary tumors after drug treatment, but not before or during
      treatment, significantly enhanced the lethal effects of UCN-01 and MEK1/2
      inhibitor treatment. These findings argue that UCN-01 and multiple inhibitors of
      the RAS-MEK pathway have the potential to suppress mammary tumor growth, and to
      interact with radiation, in vitro and in vivo.

PMID- 18347149
TI  - Effects of sustained and intermittent paclitaxel therapy on tumor repopulation in
      ovarian cancer.
AB  - Tumor repopulation between cycles of chemotherapy likely has a negative effect on
      clinical outcome in ovarian cancer patients. Thus, avoiding treatment-free
      periods when tumor cells proliferate by providing sustained chemotherapy regimens
      may improve clinical response. We investigated the effect of sustained versus
      intermittent paclitaxel administration on tumor repopulation in ovarian cancer.
      Growth, clonogenic survival, and apoptosis were followed in SKOV3 and A2780 cells
      after equivalent exposure to intermittent and sustained levels of paclitaxel. In
      vivo tumor repopulation in response to sustained and intermittent paclitaxel
      therapy was investigated in an i.p. xenograft model of human ovarian cancer.
      Tumor growth, proliferation, and apoptosis were evaluated at different intervals
      during and after the course of treatment using 5-bromo-2-deoxyuridine uptake,
      caspase-3, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end
      labeling immunoassays. Sustained treatment significantly reduced survival in
      vitro in both cell lines, whereas an increase in clonogenic survival was observed
      in the intermittent group with each treatment gap, indicating a gradual
      acceleration in repopulation rates. Similarly, in vivo, sustained therapy
      resulted in a significant reduction of tumor growth and proliferation.
      Intermittent therapy resulted in increased tumor proliferation and no efficacy.
      The percentage of apoptotic tumor cells significantly increased in the sustained
      group, whereas no significant changes were seen in the control and intermittent
      groups. Intermittent administration of paclitaxel significantly augmented both in
      vitro and in vivo tumor repopulation rates, whereas sustained delivery inhibited
      tumor growth and repopulation. Sustained administration of paclitaxel may
      increase chemoresponsiveness and clinical response in ovarian cancer by
      attenuating tumor repopulation.

PMID- 18347150
TI  - Antiangiogenic effect of gemcitabine following metronomic administration in a
      pancreas cancer model.
AB  - Gemcitabine shows a marked antitumor effect as a result of its cytotoxic action
      toward proliferative cells. In this article, we aim to investigate the potential
      antitumor and antiangiogenic effect of gemcitabine following a metronomic
      schedule that involves the regular administration of cytotoxic drugs at doses
      lower than standard treatment. In vitro results showed that human endothelial
      cells are more sensitive to gemcitabine (IC(50) 3 nmol/L) than pancreatic tumor
      cells (IC(50) 20 nmol/L). For in vivo studies, we used an orthotopic implantation
      model of human pancreatic carcinoma in nude mice. Gemcitabine was administered
      i.p. following a low-dose schedule (1 mg/kg/d for a month) and compared with the
      conventional schedule (100 mg/kg days 0, 3, 6, and 9 postimplantation).
      Metronomic treatment effect on established tumor was equivalent to standard
      administration. The measure of CD31 endothelial marked area allowed us to show an
      in vivo antiangiogenic effect of this drug that was further enhanced by using
      metronomic administration. This effect correlated with an induction of
      thrombospondin-1, a natural inhibitor of angiogenesis. Our results allow us to
      hypothesize that, in addition to a direct antiproliferative or cytotoxic
      antiendothelial cell effect, a secondary effect involving thrombospondin-1
      induction might provide an explanation for the specificity of the effects of
      metronomic gemcitabine treatment.

PMID- 18347151
TI  - Differential effects of prostate cancer therapeutics on neuroendocrine
      transdifferentiation.
AB  - Androgen ablation therapy is widely used for the treatment of advanced prostate
      cancer. However, the effectiveness of this intervention strategy is generally
      short-lived as the disease ultimately progresses to a hormone-refractory state.
      In recent years, it has become clear that even in antiandrogen-resistant cancers
      the androgen receptor (AR) signaling axis is intact and is required for prostate
      cancer growth. Thus, there is a heightened interest in developing small molecules
      that function in part by down-regulating AR expression in tumors. Paradoxically,
      AR expression has been shown to be important in preventing the
      transdifferentiation of epithelial prostate cancer cells toward a neuroendocrine
      phenotype associated with tumor progression. Consequently, we have evaluated the
      relative effect of prostate cancer therapeutics that function in part by
      depleting AR levels on neuroendocrine differentiation in established cellular
      models of prostate cancer. These studies reveal that although histone deacetylase
      inhibitors can down-regulate AR expression they increase the expression of
      neuroendocrine markers and alter cellular morphology. Inhibition of AR signaling
      using classic AR antagonists or small interfering RNA-mediated AR ablation
      induces incomplete neuroendocrine differentiation. Importantly, the Hsp90
      inhibitor geldanamycin effectively down-regulates AR expression while having no
      effect on neuroendocrine differentiation. Taken together, these data show that
      the phenotypic responses to pharmacologic agents used in the clinic to prevent
      the progression of prostate cancer are not equivalent, a finding of significant
      therapeutic importance.

PMID- 18347152
TI  - Doxorubicin activates FOXO3a to induce the expression of multidrug resistance
      gene ABCB1 (MDR1) in K562 leukemic cells.
AB  - Using the doxorubicin-sensitive K562 cell line and the resistant derivative lines
      KD30 and KD225 as models, we found that acquisition of multidrug resistance (MDR)
      is associated with enhanced FOXO3a activity and expression of ABCB1 (MDR1), a
      plasma membrane P-glycoprotein that functions as an efflux pump for various
      anticancer agents. Furthermore, induction of ABCB1 mRNA expression on doxorubicin
      treatment of naive K562 cells was also accompanied by increased FOXO3a activity.
      Analysis of transfected K562, KD30, and KD225 cells in which FOXO3a activity can
      be induced by 4-hydroxytamoxifen showed that FOXO3a up-regulates ABCB1 expression
      at protein, mRNA, and gene promoter levels. Conversely, silencing of endogenous
      FOXO3a expression in KD225 cells inhibited the expression of this transport
      protein. Promoter analysis and chromatin immunoprecipitation assays showed that
      FOXO3a regulation of ABCB1 expression involves binding of this transcription
      factor to the proximal promoter region. Moreover, activation of FOXO3a increased
      ABCB1 drug efflux potential in KD30 cells, whereas silencing of FOXO3a by siRNA
      significantly reduced ABCB1 drug efflux ability. Together, these findings suggest
      a novel mechanism that can contribute towards MDR, involving FOXO3a as sensor for
      the cytotoxic stress induced by anticancer drugs. Although FOXO3a may initially
      trigger a program of cell cycle arrest and cell death in response to doxorubicin,
      sustained FOXO3a activation promotes drug resistance and survival of cells by
      activating ABCB1 expression.

PMID- 18347153
TI  - Modulation of survival pathways in ovarian carcinoma cell lines resistant to
      platinum compounds.
AB  - Because cytotoxic stress elicits various signaling pathways that may be
      implicated in cell survival or cell death, their alterations may have relevance
      in the development of platinum-resistant phenotype. Thus, in the present study,
      we investigated cell response to the epidermal growth factor receptor (EGFR)
      inhibitor gefitinib of ovarian carcinoma cell lines, including cells selected for
      resistance to cisplatin (IGROV-1/Pt1) and oxaliplatin (IGROV-1/OHP). Resistant
      sublines exhibited a marked decrease in sensitivity to gefitinib and resistance
      to apoptosis. Gefitinib was capable of inhibiting the phosphorylation of EGFR in
      all the studied cell lines. The Akt and extracellular signal-regulated kinase 1/2
      (ERK1/2) kinases, which act downstream of EGFR, were constitutively active in the
      three cell lines, but phospho-ERK1/2 levels were increased in the two resistant
      sublines. This feature was associated with reduced sensitivity to the MEK1/2
      inhibitor U0126. Pretreatment of resistant cells with U0126 resulted in
      restoration of sensitivity to gefitinib. Gefitinib was more effective in
      inhibiting ERK1/2 and Akt phosphorylation in IGROV-1 cells than in IGROV-1/OHP
      and IGROV-1/Pt1 cells. Phospho-p38 was up-regulated in the resistant sublines,
      indicating the concomitant activation of distinct mitogen-activated protein
      kinases. The up-regulation of phospho-p38 was associated with a peculiar
      localization of EGFR, which, in resistant sublines, was mainly internalized. In
      conclusion, our results indicate that the development of resistance to platinum
      drugs is associated with multiple alterations including deregulation of survival
      pathways activated by EGFR resulting in a reduced cellular response to gefitinib.

PMID- 18347154
TI  - Antitumor effect of dsRNA-induced p21(WAF1/CIP1) gene activation in human bladder
      cancer cells.
AB  - We recently reported that synthetic dsRNAs targeting promoter regions can induce
      gene expression in a phenomenon referred to as dsRNA-induced gene activation/RNA
      activation (RNAa) [Li et al. Proc Natl Acad Sci U S A 2006;103:17337-42]. The
      present study investigates the in vitro antitumor activity RNAa can elicit
      through triggering the expression of cell cycle repressor protein p21(WAF1/CIP1)
      (p21) in human bladder cancer cells. Transfection of a 21-nucleotide dsRNA
      targeting the p21 promoter (dsP21) was used to induce p21 expression in T24 and
      J82 bladder cancer cell lines. Reverse transcription-PCR and Western blot
      analysis accessed the increase p21 mRNA and protein levels, respectively, in
      transfected cells. In association to p21 induction, dsP21 transfection
      significantly inhibited bladder cancer cell proliferation and clonogenicity.
      Further analysis of cell viability and cell cycle distribution revealed that
      dsP21 transfection also enhanced apoptotic cell death and caused an accumulation
      in the G(1) phase in both cell lines. In conclusion, p21 activation by RNAa has
      antitumor activity in vitro in bladder cancer cells. These results suggest that
      RNAa could be used for cancer treatment by targeted activation of tumor
      suppressor genes.

PMID- 18347155
TI  - Overexpression of PTEN in ovarian cancer cells suppresses i.p. dissemination and
      extends survival in mice.
AB  - The main mode of progression of ovarian cancer is peritoneal dissemination, and
      its inhibition may lead to improved outcome. Phosphatase and tensin homologue
      deleted on chromosome 10 (PTEN) reportedly inhibits the proliferation, migration,
      and invasion of cancer cells. The purpose of this study is to explore the
      possibility of PTEN gene therapy for ovarian cancer. We transfected the ovarian
      cancer cell line SHIN-3 [vascular endothelial growth factor (VEGF)-hypersecretory
      cell line] with PTEN or luciferase (LUC)-expressing plasmid. After selection,
      PTEN-overexpressing cells (SHIN-3/PTEN) and control cells (SHIN-3/LUC) were
      obtained. SHIN-3/PTEN implanted s.c. into nude mice was examined for the change
      in tumor diameter and the number of new blood vessels. Mice with peritoneally
      disseminated tumors created by i.p. inoculation of the same cells were examined
      for changes in body weight and abdominal circumference and for survival time. The
      growth of s.c. SHIN-3/PTEN was significantly lower than that of control (P <
      0.001). Compared with controls, mice with i.p. inoculated SHIN-3/PTEN showed
      significantly smaller increases in the body weight and abdominal circumference (P
      < 0.01) and a significantly longer survival time (P < 0.05). VEGF concentration
      in the supernatant of SHIN-3/PTEN was about half that of controls (P < 0.05). The
      number of new blood vessels in SHIN-3/PTEN was significantly smaller than that in
      controls (P < 0.001). Overexpression of PTEN suppressed tumor growth and
      peritoneal dissemination of VEGF-hypersecretory ovarian cancer cells and
      prolonged the survival time of the mice with peritoneal disseminated tumor. PTEN
      gene therapy could have therapeutic potential for ovarian cancer and exerts some
      of this effect by inhibiting angiogenesis.

PMID- 18347156
TI  - Blockade of viral interleukin-6 expression of Kaposi's sarcoma-associated
      herpesvirus.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus
      8, is associated with several malignant disorders, including Kaposi's sarcoma,
      primary effusion lymphoma (PEL), and multicentric Castleman's disease. An early
      lytic gene of KSHV encodes viral interleukin-6 (vIL-6), a viral homologue of the
      proinflammatory cytokine and an autocrine/paracrine growth factor human IL-6. In
      this study, we examined the effects of suppressing vIL-6 expression in PEL cells
      with antisense peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO).
      PPMO are ssDNA-analogues that have a modified backbone and enter cells readily.
      Treatment of PEL cells with a PPMO designed against vIL-6 mRNA led to a marked
      reduction in the proportion of vIL-6-positive cells detected by
      immunofluorescence assay. Analysis by Western blot confirmed a specific reduction
      in the vIL-6 protein level and showed that the reduction was dependent on the
      dose of vIL-6 PPMO. PEL cells treated with the vIL-6 PPMO exhibited reduced
      levels of cellular growth, IL-6 expression and KSHV DNA, and an elevated level of
      p21 protein. Treatment of PEL cells with a combination of two vIL-6 PPMO
      compounds targeting different sequences in the vIL-6 mRNA led to an inhibitory
      effect that was greater than that achieved with either PPMO alone. These results
      show that PPMO targeting vIL-6 mRNA can potently reduce vIL-6 protein translation
      and indicate that further exploration of these compounds in an animal model for
      potential clinical application is warranted.

PMID- 18347157
TI  - A chaperone protein-enriched tumor cell lysate vaccine generates protective
      humoral immunity in a mouse breast cancer model.
AB  - We have documented previously that a multiple chaperone protein vaccine termed
      chaperone-rich cell lysate (CRCL) promotes tumor-specific T-cell responses
      leading to cancer regression in several mouse tumor models. We report here that
      CRCL vaccine generated from a mouse breast cancer (TUBO, HER2/neu positive) is
      also capable of eliciting humoral immunity. Administration of TUBO CRCL triggered
      anti-HER2/neu antibody production and delayed the progression of established
      tumors. This antitumor activity can be transferred through the serum isolated
      from TUBO CRCL-immunized animals and involved both B cells and CD4(+) T
      lymphocytes. Further evaluation of the mechanisms underlying TUBO CRCL-mediated
      humoral immunity highlighted the role of antibody-dependent cell-mediated
      cytotoxicity. These results suggest that tumor-derived CRCL vaccine has a wider
      applicability as a cancer vaccine because it can target both T-cell- and B-cell
      specific responses and may represent a promising approach for the immunotherapy
      of cancer.

PMID- 18347158
TI  - Preclinical modeling of cytosine arabinoside response in Mll-Enl translocator
      mouse leukemias.
AB  - Mouse models of human cancer are a potential preclinical setting for drug testing
      and for development of methods for delivery of macromolecular drugs to tumors. We
      have assessed a mouse model of leukemia caused by Mll-Enl protein fusion as a
      preclinical situation in which myeloid-lineage leukemia results from de novo
      occurrence of chromosomal translocations between Mll and Enl genes. Here, we show
      that the mouse leukemias respond to cytosine arabinoside, a frontline treatment
      for human leukemia. The observations show that the myeloid cells are susceptible
      to the drug and the mice undergo a remission that comprises a reduction of the
      myeloid population of cells and recovery of the lymphoid population. This
      translocator model should therefore prove useful for future drug assessments
      against the recurrent mixed-lineage leukemia-associated translocations.

PMID- 18347159
TI  - Understanding the biology of bone metastases: key to the effective treatment of
      prostate cancer.
AB  - Advanced prostate cancer is dominated by bone-forming osseous metastases.
      Understanding the biology behind this striking clinical manifestation is the key
      to its effective treatment. A clinical trial using a bone-targeting
      radiopharmaceutical agent, strontium 89, combined with chemotherapy showed
      increased survival time among patients with progression of prostate cancer in
      bone, suggesting that therapeutic strategies focused on treating the tumor in
      bone are effective. We and others thus hypothesize that interactions between
      prostate cancer cells and the bone microenvironment play a role in the
      progression of prostate cancer in bone. Clinical trials and basic science
      investigations aiming to understand such interactions have been carried out in
      parallel. In the laboratory studies, human bone marrow specimens have been
      collected for identification of proteins involved in the bidirectional
      interactions between prostate cancer cells and bone. In addition, specimens from
      bone biopsies of the cancer lesions have been used to generate xenografts in
      animals to establish animal models for testing therapeutic strategies. Clinical
      trials using agents to inhibit the stromal-prostate cancer interactions (e.g.,
      docetaxel/imatinib or thalidomide) have been done. Analyses of the specimens from
      these trials provided support of our hypothesis and future development of
      diagnosis and therapy strategies.

PMID- 18347160
TI  - Capitalizing on the immunogenicity of dying tumor cells.
AB  - Cancer cell death occurs continually during tumor development and progression,
      whereas the selective killing of surviving cancer cells remains the primary
      objective of antineoplastic treatments. Recent insights into the immunologic
      consequences of cancer cell death have begun to elucidate the ways in which host
      antitumor immunity is shaped during cancer pathogenesis and then modulated by
      therapeutic intervention. Dying tumor cells evoke a range of host responses,
      dependent in part upon the mode of cell death, which may either impede or foster
      additional immune-mediated cancer destruction. Within the tumor microenvironment,
      the capture of apoptotic tumor cells by macrophages and dendritic cells may
      trigger tolerance networks that contribute to immune suppression, whereas the
      uptake of necrotic cancer cells may engender inflammatory pathways that fuel
      antitumor cytotoxicity. Milk fat globule epidermal growth factor 8, a
      phosphatidylserine-binding protein, and MHC class I chain-related protein A, an
      NKG2D ligand, play key roles in these competing outcomes. A deeper understanding
      of the mechanisms underlying the immunogenicity of dying cells informs the
      crafting of strategies that exploit endogenous or treatment-induced cancer cell
      death as the basis for stimulating sustained host antitumor cytotoxic reactions.

PMID- 18347161
TI  - Newer cytotoxic agents: attacking cancer broadly.
AB  - The plasticity and instability of the cancer genome is impressive and is
      characterized by gene amplifications and deletions, rearrangements, and many
      silent and active mutations. Although targeted therapeutics have had effect in
      some diseases, there remains a large role for new cytotoxic agents that have the
      potential to be broadly active across multiple cancers. Platinum-based regimens
      are the basis for treatment of several common tumors. Satraplatin and picoplatin
      are newer platinum complexes that form bulkier lesions in DNA than their
      forerunners. Microtubules are a key target for anticancer agents. Vinca alkaloid
      and similar compounds fragment these critical structures, whereas taxanes
      stabilize them. Vinflunine is a new fluorinated Vinca alkaloid derivative with
      vascular disrupting effects, as well as antitumor effects. Epothilones are a new
      class of microtubule stabilizers. Mitosis has been targeted directly and
      indirectly by many anticancer agents. The aurora kinases are new targets in this
      class. Inhibitors of aurora kinases are likely to be cytotoxic. Finally, protein
      regulation is essential for cellular integrity. With the approval of bortezomib
      (Velcade, PS-341), the proteosome, a master protein regulator, has been validated
      as an anticancer target. The five articles in this issue of CCR Focus present the
      current status of these next generation cytotoxic agents.

PMID- 18347162
TI  - The epothilones: translating from the laboratory to the clinic.
AB  - The epothilones are macrolide compounds that have been shown to stabilize
      microtubules. The epothilones are strong promoters of tubulin polymerization in
      vitro and have significant antitumor activity against human cancer cells that are
      taxane resistant, express the multidrug resistance gene MDR-1 (ABCB1), and have
      acquired tubulin mutations. Several epothilones have been evaluated in clinical
      trials in a variety of tumor types. Ixabepilone (aza-epothilone B) has
      significant antitumor activity in breast cancer resistant to an anthracycline and
      a taxane, and has been approved by the U.S. Food and Drug Administration for the
      treatment of patients with metastatic or locally advanced breast cancer. There
      have been sustained efforts to develop pharmacodynamic markers to monitor the
      pharmacologic effect of the epothilones on tumors and normal tissues. The
      development of predictive markers for epothilone chemotherapy is highly desired
      to provide more tailored therapy for patients with cancer.

PMID- 18347163
TI  - Vinflunine: a new microtubule inhibitor agent.
AB  - Vinflunine (Javlor) is the first fluorinated microtubule inhibitor belonging to
      the Vinca alkaloids family. Vinflunine is obtained by semisynthesis using
      superacidic chemistry to selectively introduce two fluorine atoms at the 20'
      position of the catharanthine moiety. This compound has been selected for
      clinical development on the basis of encouraging preclinical activity that
      warrants study in patients with a wide spectrum of solid tumors. Clinically
      significant activity has been seen in phase II studies, mainly in the treatment
      of transitional cell carcinoma of the urothelial tract, non-small cell lung
      cancer, and carcinoma of the breast. Vinflunine is currently in phase III trial
      assessment in patients with (second line) transitional cell carcinoma of the
      urothelium and first-line advanced breast cancer. The efficacy of vinflunine in
      patients with advanced non-small cell lung cancer previously treated with a
      platinum-containing regimen was confirmed by a large phase III trial.

PMID- 18347164
TI  - Current status and future prospects for satraplatin, an oral platinum analogue.
AB  - Platinum drugs are major chemotherapeutic agents that are used alone or in
      combination with other systemic agents and/or radiation therapy in the management
      of many human malignancies. All three platinum drugs approved by the Food and
      Drug Administration, cisplatin, carboplatin, and oxaliplatin, are administrated
      intravenously. Satraplatin is the first orally administered platinum drug under
      active clinical investigation. Satraplatin and its major metabolite, JM118, have
      shown antineoplastic activity in in vitro, in vivo, and in clinical settings. Use
      of satraplatin as an alternative platinum cytotoxic agent is particularly
      attractive because of the convenience of administration, milder toxicity profile,
      lack of cross-resistance with cisplatin, theoretical advantage as a
      radiosensitizer, and activity in cancers historically nonresponsive to platinum
      drugs. The most mature clinical data for satraplatin come from the recently
      completed phase III trial that investigated the efficacy of satraplatin and
      prednisone on hormone-refractory prostate cancer patients who had failed a course
      of other chemotherapy agents. Preliminary reports show that the combination is
      statistically superior to placebo and prednisone in multiple end points,
      including progression-free survival, prostate-specific antigen response,
      objective tumor response, pain response, and duration of pain response. The
      difference in overall survival, however, did not reach statistical significance.

PMID- 18347165
TI  - Aurora kinases as anticancer drug targets.
AB  - The human aurora family of serine-threonine kinases comprises three members,
      which act in concert with many other proteins to control chromosome assembly and
      segregation during mitosis. Aurora dysfunction can cause aneuploidy, mitotic
      arrest, and cell death. Aurora kinases are strongly expressed in a broad range of
      cancer types. Aurora A expression in tumors is often associated with gene
      amplification, genetic instability, poor histologic differentiation, and poor
      prognosis. Aurora B is frequently expressed at high levels in a variety of
      tumors, often coincidently with aurora A, and expression level has also been
      associated with increased genetic instability and clinical outcome. Further,
      aurora kinase gene polymorphisms are associated with increased risk or early
      onset of cancer. The expression of aurora C in cancer is less well studied. In
      recent years, several small-molecule aurora kinase inhibitors have been developed
      that exhibit preclinical activity against a wide range of solid tumors.
      Preliminary clinical data from phase I trials have largely been consistent with
      cytostatic effects, with disease stabilization as the best response achieved in
      solid tumors. Objective responses have been noted in leukemia patients, although
      this might conceivably be due to inhibition of the Abl kinase. Current challenges
      include the optimization of drug administration, the identification of potential
      biomarkers of tumor sensitivity, and combination studies with cytotoxic drugs.
      Here, we summarize the most recent preclinical and clinical data and discuss new
      directions in the development of aurora kinase inhibitors as antineoplastic
      agents.

PMID- 18347166
TI  - Proteasome inhibitors in cancer therapy: lessons from the first decade.
AB  - The ubiquitin-proteasome pathway is involved in intracellular protein turnover,
      and its function is crucial to cellular homeostasis. First synthesized as probes
      of proteolytic processes, proteasome inhibitors began to be thought of as
      potential drug candidates when they were found to induce programmed cell death
      preferentially in transformed cells. They made their first leap into the clinic
      to be tested as therapeutic agents 10 years ago, and since then, great strides
      have been made in defining their mechanisms of action, their clinical efficacy
      and toxicity, and some of their limitations in the form of resistance pathways.
      Validation of the ubiquitin-proteasome pathway as a target for cancer therapy has
      come in the form of approvals of the first such inhibitor, bortezomib, for
      relapsed/refractory multiple myeloma and mantle cell lymphoma, for which this
      agent has become a standard of care. Lessons learned from this first-in-class
      agent are now being applied to the development of a new generation of proteasome
      inhibitors that hold the promise of efficacy in bortezomib-resistant disease and
      possibly in a broader spectrum of diseases. This saga provides a salient example
      of the promise of translational medicine and a paradigm by which other agents may
      be successfully brought from the bench to the bedside.

PMID- 18347167
TI  - Class I histone deacetylase expression has independent prognostic impact in human
      colorectal cancer: specific role of class I histone deacetylases in vitro and in
      vivo.
AB  - PURPOSE: Recently, several studies reported a strong functional link between
      histone deacetylases (HDAC) and the development of tumors of the large intestine.
      However, despite the importance of these molecules, comparably little is known on
      expression patterns and functions of specific HDAC isoforms in colorectal cancer.
      EXPERIMENTAL DESIGN: We characterized class I HDAC isoform expression patterns in
      a cohort of 140 colorectal carcinomas by immunohistochemistry. In addition,
      effects of HDAC inhibition by valproic acid and suberoylanilide hydroxamic acid,
      and specific HDAC isoform knockdown by short interfering RNA, were investigated
      in a cell culture model. RESULTS: We found class I HDACs highly expressed in a
      subset of colorectal carcinomas with positivity for HDAC1 in 36.4%, HDAC2 in
      57.9%, and HDAC3 in 72.9% of cases. Expression was significantly enhanced in
      strongly proliferating (P = 0.002), dedifferentiated (P = 0.022) tumors. High
      HDAC expression levels implicated significantly reduced patient survival (P =
      0.001), with HDAC2 expression being an independent survival prognosticator
      (hazard ratio, 2.6; P = 0.03). Short interfering RNA-based inhibition of HDAC1
      and HDAC2 but not HDAC3 suppressed growth of colon cancer cells in vitro,
      although to a lesser extent than chemical HDAC inhibitors did. CONCLUSIONS: The
      strong prognostic impact of HDAC isoforms in colorectal cancer, the interactions
      of HDACs with tumor cell proliferation and differentiation in vivo, and our
      finding that HDACs are differentially expressed in colorectal tumors suggest that
      the evaluation of HDAC expression in clinical trials for HDAC inhibitors might
      help to identify a patient subgroup who will exceptionally profit from such a
      treatment.

PMID- 18347168
TI  - Endothelial differentiation of hematopoietic stem and progenitor cells from
      patients with multiple myeloma.
AB  - PURPOSE: Vasculogenesis is a physiologic process typical of fetal development in
      which new blood vessels develop from undifferentiated precursors (or
      angioblasts). In tumors, near angiogenesis, vasculogenesis contributes to the
      formation of the microvascular plexus that is important for diffusion. Here, we
      show that hematopoietic stem and progenitor cells (HSPC) of multiple myeloma (MM)
      patients are able to differentiate into cells with endothelial phenotype on
      exposure to angiogenic cytokines. EXPERIMENTAL DESIGN: Circulating HSPCs were
      purified with an anti-CD133 antibody from patients with newly diagnosed MM before
      autologous transplantation and exposed to vascular endothelial growth factor
      (VEGF), fibroblast growth factor-2 and insulin-like growth factor in a 3-week
      culture. RESULTS: HSPCs gradually lost CD133 expression and acquired VEGF
      receptor-2, factor VIII-related antigen, and vascular endothelial-cadherin
      expression. The expression pattern overlapped with paired MM endothelial cells
      (MMEC). During culture, cells adhered to fibronectin, spread, and acquired an
      endothelial cell shape. Differentiated HSPCs also became capillarogenic in the
      Matrigel assay with maximal activity at the third week of culture. Bone marrow
      biopsies revealed HSPCs inside the neovessel wall in patients with MM but not in
      those with monoclonal gammopathy of undetermined significance. CONCLUSIONS: In
      patients with MM, but not in those with monoclonal gammopathy of undetermined
      significance, HSPCs contribute to the neovessel wall building together with
      MMECs. Therefore, besides angiogenesis, HSPC-linked vasculogenesis contributes to
      neovascularization in MM patients. Tentatively, we hypothesize that in HSPC
      cultures a multipotent cell population expressing low VEGF receptor-2 levels
      corresponds to the endothelial progenitor cell precursor and seems to be the MMEC
      precursor.

PMID- 18347169
TI  - Expression of the bric-a-brac tramtrack broad complex protein NAC-1 in cervical
      carcinomas seems to correlate with poorer prognosis.
AB  - PURPOSE: Recent studies have suggested a novel oncogenic role of a bric-a-brac
      tramtrack broad complex (also known as POZ) domain gene, NAC-1, in ovarian
      carcinomas. The aim of this study was to clarify the functional role of NAC-1 in
      human cervical carcinomas. EXPERIMENTAL DESIGN: NAC-1 expression in cervical
      cancer was assessed by immunohistochemistry, and data on clinical variables were
      collected by retrospective chart review. NAC-1 gene knockdown using small
      interfering RNA and a NAC-1 gene transfection system were used to asses NAC-1
      function in cervical cancer in vivo. RESULTS: Immunohistochemical and gene
      expression analysis revealed that NAC-1 is significantly overexpressed in
      cervical adenocarcinomas and adenosquamous carcinomas compared with squamous cell
      carcinomas. Patients with squamous cell carcinomas positive for NAC-1 expression
      who received radiotherapy had significantly shorter overall survival than peers
      whose tumors did not express NAC-1, and multivariate analysis showed that NAC-1
      expression was an independent prognostic factor for overall survival after
      radiotherapy. Overexpressions of the NAC-1 gene stimulated cell proliferation in
      cervical carcinoma cells of the TCS, CaSki, and HeLa P3 lines, which do not have
      endogenous NAC-1 expression. NAC-1 gene knockdown inhibited cell growth and
      induced apoptosis in HeLa, HeLa TG, and ME180 cells, all of which overexpressed
      NAC-1. CONCLUSIONS: Our findings suggest that NAC-1 may play an important role in
      cervical carcinomas; moreover, these findings provide a rationale for future
      development of NAC-1-based therapy for cervical carcinomas that overexpress this
      candidate oncogene.

PMID- 18347170
TI  - IMP3 predicts aggressive superficial urothelial carcinoma of the bladder.
AB  - PURPOSE: In this study, we investigated whether an oncofetal protein, IMP3, can
      serve as a new biomarker to predict progression and metastasis of early-stage
      urothelial carcinoma of the bladder. EXPERIMENTAL DESIGN: The expression of IMP3
      in 242 patients with primary superficial bladder urothelial carcinoma and
      metastatic urothelial carcinoma was evaluated by immunohistochemistry. Patients
      with primary superficial urothelial carcinoma of the bladder were further
      investigated by use of survival analysis. RESULTS: Twenty percent (42 of 214) of
      primary superficial urothelial carcinomas and 93% (26 of 28) of metastatic
      urothelial carcinomas expressed IMP3. Kaplan-Meier plots and log-rank tests
      showed that patients with IMP3-positive tumors had a much lower progression-free
      survival (P = 0.0002) and disease-free survival rate (P = 0.0067) than did those
      with IMP3-negative tumors. The 5-year progression-free and disease-free survival
      rates were 91% and 94% in IMP3-negative patients versus 64% and 76% in IMP3
      positive patients, respectively. Sixty percent of IMP3-positive patients with
      superficial invasive urothelial carcinoma at initial diagnosis went on to develop
      metastases, whereas no metastasis was found in IMP3-negative patients (P =
      0.0017). In the multivariable Cox analysis, patients with IMP3 expression in
      their superficial urothelial carcinomas subsequently developed invasive tumors or
      metastasis at a rate that was about five times greater than cases without
      expression of IMP3 adjusting for other well-known clinical variables (tumor stage
      and grade, etc.). CONCLUSIONS: Our findings indicate that IMP3 is an independent
      prognostic marker that can identify a group of patients with a high potential to
      develop progression and who might benefit from early aggressive therapy.

PMID- 18347171
TI  - Pfetin as a prognostic biomarker of gastrointestinal stromal tumors revealed by
      proteomics.
AB  - PURPOSE: We aimed to develop prognostic biomarkers for gastrointestinal stromal
      tumors (GIST) using a proteomic approach. EXPERIMENTAL DESIGN: We examined the
      proteomic profile of GISTs using two-dimensional difference gel electrophoresis.
      The prognostic performance of biomarker candidates was examined using a large
      scale sample set and specific antibodies. RESULTS: We identified 43 protein spots
      whose intensity was statistically different between GISTs with good and poor
      prognosis. Mass spectrometric protein identification showed that the 43 spots
      corresponded to 25 distinct gene products. Eight of the 43 spots derived from
      pfetin, a potassium channel protein, and four of the eight pfetin spots had a
      high discriminative power between the two groups. Western blotting and real-time
      PCR showed that pfetin expression and tumor metastasis were inversely related.
      The prognostic performance of pfetin was also examined by immunohistochemistry on
      210 GIST cases. The 5-year metastasis-free survival rate was 93.9% and 36.2% for
      patients with pfetin-positive and pfetin-negative tumors, respectively (P <
      0.0001). Univariate and multivariate analyses revealed that pfetin expression was
      a powerful prognostic factor among the clinicopathologic variables examined,
      including risk classification and c-kit- or platelet-derived growth factor
      receptor A mutation status. CONCLUSIONS: These results establish pfetin as a
      powerful prognostic marker for GISTs and may provide novel therapeutic strategies
      to prevent metastasis of GIST.

PMID- 18347172
TI  - Prognostic value of body mass index in locally advanced breast cancer.
AB  - PURPOSE: The purpose of this retrospective study was to determine the association
      and prognostic value of body mass index (BMI) at the time of initial diagnosis in
      patients with locally advanced breast cancer (LABC). The analysis includes the
      subsets of inflammatory (IBC) and noninflammatory (non-IBC LABC) breast cancer.
      EXPERIMENTAL DESIGN: We identified 602 patients who had LABC treated on
      prospective clinical trials. BMI was divided into three groups: (a) < or =24.9
      (normal/underweight), (b) 25.0 to 29.9 (overweight), and (c) > or =30 (obese).
      Kaplan-Meier product limit method was used to estimate survival outcomes. Cox
      proportional hazards were used to determine associations between survival and BMI
      and to test for an interaction between BMI and breast cancer type. RESULTS:
      Eighty-two percent had non-IBC LABC and 18% had IBC. Obese patients tended to
      have a higher incidence of IBC compared with overweight and normal/underweight
      groups (P = 0.01). Median follow up was 6 years for all patients. Median overall
      survival (OS) and recurrence-free survival (RFS) were 8.8 and 5.9 years,
      respectively. Patients with LABC who were obese or overweight had a significantly
      worse OS and RFS (P = 0.001) and a higher incidence of visceral recurrence
      compared with normal/underweight patients. In a multivariable model, BMI remained
      significantly associated with both OS and RFS for the entire cohort. The
      interactions between BMI and LABC subsets and between BMI and menopausal status
      were not statistically significant. CONCLUSION: Patients with LABC and high BMI
      have a worse prognosis. Evaluation of the biological factors associated with this
      observation can provide tools for additional therapeutic interventions.

PMID- 18347173
TI  - Subcellular localization of activated leukocyte cell adhesion molecule is a
      molecular predictor of survival in ovarian carcinoma patients.
AB  - PURPOSE: Currently available clinicopathologic prognostic factors are imperfect
      predictors of clinical course in advanced-stage epithelial ovarian cancer
      patients. New molecular predictors are needed to identify patients with higher
      risk of relapse or death from disease. In a retrospective study, we investigated
      the prognostic impact of activated leukocyte cell adhesion molecule (ALCAM)
      expression in epithelial ovarian cancer. EXPERIMENTAL DESIGN: We analyzed the
      effect of cell-anchorage loss on ALCAM cellular localization in vitro and
      assessed ALCAM expression by immunohistochemistry in a series of 109 well
      characterized epithelial ovarian cancer patient samples. Chi-square test, Kaplan
      Meier method, and Cox proportional hazard analyses were used to relate ALCAM
      cellular localization to clinical-pathologic parameters and to overall survival
      (OS) rate. RESULTS: Loss of epithelial ovarian cancer cell anchorage was
      associated both in vitro and in vivo with decreased ALCAM membrane expression. In
      vivo, ALCAM was localized to cell membrane in normal surface ovarian epithelium,
      whereas in 67% of the epithelial ovarian cancer samples, membrane localization
      was decreased or even lost, and the molecule was mainly expressed in cytoplasm.
      Median OS in this group of patients was 58 months, whereas a median OS was not
      yet reached in patients with ALCAM membrane localization (P = 0.036, hazard ratio
      [HR] = 2.0, 95% confidence interval [CI] 1.1 to 3.5). In a multivariate Cox
      regression model including all the available clinicopathologic variables, loss of
      ALCAM membrane expression was an independent factor of unfavorable prognosis (P =
      0.042, HR = 2.15, 95% CI: 1.0 to 4.5). CONCLUSIONS: Decreased/lost ALCAM membrane
      expression is a marker of poorer outcome in epithelial ovarian cancer patients
      and might help to identify patients who could benefit from more frequent follow
      up or alternative therapeutic modalities.

PMID- 18347174
TI  - Identification of prognostic biomarkers for prostate cancer.
AB  - PURPOSE: This paper describes a process for the identification of genes that can
      report on the aggressiveness of prostate tumors and thereby add to the
      information provided by current pathologic analysis. MATERIALS AND METHODS:
      Expression profiling data from over 100 laser capture microdissection derived
      samples from nonneoplastic epithelium; Gleason patterns 3, 4, and 5 and node
      metastasis prostate cancer were used to identify genes at abnormally high levels
      in only some tumors. These variably overexpressed genes were stratified by their
      association with aggressive phenotypes and were subsequently filtered to exclude
      genes with redundant expression patterns. Selected genes were validated in a case
      control study in which cases (systemic progression within 5 years) and controls
      (no systemic progression at 7 years of follow-up) were matched for all clinical
      and pathologic criteria from time of prostatectomy (n = 175). Both cases and
      controls, therefore, could have nodal invasion or seminal vesicle involvement at
      the time of initial treatment. RESULTS: A number of candidate variably
      overexpressed genes selected for their association with aggressive prostate
      cancer phenotype were evaluated in the case control study. The most prominent
      candidates were SSTR1 and genes related to proliferation, including TOP2A.
      CONCLUSIONS: The process described here identified genes that add information not
      available from current clinical measures and can improve the prognosis of
      prostate cancer.

PMID- 18347175
TI  - A gene expression signature that can predict the recurrence of tamoxifen-treated
      primary breast cancer.
AB  - PURPOSE: The identification of a molecular signature predicting the relapse of
      tamoxifen-treated primary breast cancers should help the therapeutic management
      of estrogen receptor-positive cancers. EXPERIMENTAL DESIGN: A series of 132
      primary tumors from patients who received adjuvant tamoxifen were analyzed for
      expression profiles at the whole-genome level by 70-mer oligonucleotide
      microarrays. A supervised analysis was done to identify an expression signature.
      RESULTS: We defined a 36-gene signature that correctly classified 78% of patients
      with relapse and 80% of relapse-free patients (79% accuracy). Using 23
      independent tumors, we confirmed the accuracy of the signature (78%) whose
      relevance was further shown by using published microarray data from 60 tamoxifen
      treated patients (63% accuracy). Univariate analysis using the validation set of
      83 tumors showed that the 36-gene classifier is more efficient in predicting
      disease-free survival than the traditional histopathologic prognostic factors and
      is as effective as the Nottingham Prognostic Index or the "Adjuvant!" software.
      Multivariate analysis showed that the molecular signature is the only independent
      prognostic factor. A comparison with several already published signatures
      demonstrated that the 36-gene signature is among the best to classify tumors from
      both training and validation sets. Kaplan-Meier analyses emphasized its
      prognostic power both on the whole cohort of patients and on a subgroup with an
      intermediate risk of recurrence as defined by the St. Gallen criteria.
      CONCLUSION: This study identifies a molecular signature specifying a subgroup of
      patients who do not gain benefits from tamoxifen treatment. These patients may
      therefore be eligible for alternative endocrine therapies and/or chemotherapy.

PMID- 18347176
TI  - Overall and relapse-free survival in oropharyngeal and hypopharyngeal squamous
      cell carcinoma are associated with genotypes of T393C polymorphism of the GNAS1
      gene.
AB  - PURPOSE: In previous studies, we have shown that the T allele of a specific
      single-nucleotide polymorphism (SNP) in the Galphas gene (T393C) correlates with
      increased Galphas expression and hence apoptosis. The T allele was associated
      with a favorable outcome in a variety of human cancers, e.g., carcinoma of the
      urinary bladder, kidney, and colorectum. EXPERIMENTAL DESIGN: The prognostic
      value of the T393C SNP was evaluated in an unselected series of patients treated
      with curative intent for oropharyngeal and hypopharyngeal squamous cell
      carcinomas, including all tumor stages with different therapeutic regimens.
      Genotype analysis was done using DNA from paraffin-embedded tissue samples from
      202 patients (162 men, 40 women) with a median follow-up of 38 months (1-133
      months). The various genotypes were correlated with relapse-free and overall
      survival. RESULTS: GNAS1 393C homozygous patients displayed a higher risk for
      disease progression than T393 homozygous patients (hazard ratio CC versus TT,
      1.9; 95% confidence interval, 1.1-3.2; P = 0.019). The same genotype effect was
      observed for overall survival with CC genotypes at higher risk for death compared
      with TT genotypes (hazard ratio, 1.7; 95% confidence interval, 1.1-2.9; P =
      0.015). Multivariate analysis showed that, besides American Joint Committee on
      Cancer stage, tumor localization, and gender, the T393C polymorphism was an
      independent prognostic factor for disease progression and death. CONCLUSION: The
      T393C SNP could be considered as a genetic marker to predict the clinical course
      of patients suffering from oropharyngeal and hypopharyngeal cancer.

PMID- 18347177
TI  - Topoisomerase IIalpha expression as an independent prognostic factor in Hodgkin's
      lymphoma.
AB  - PURPOSE: To correlate the immunohistochemical expression of topoisomerase IIalpha
      (topoIIalpha) in Hodgkin's lymphoma (HL) with clinicopathological parameters, the
      expression of Ki-67 and the outcome of patients, who had been homogenously
      treated with ABVD or equivalent regimens. EXPERIMENTAL DESIGN:
      Immunohistochemistry using the monoclonal antibody Ki-S1 (topoIIalpha) was
      performed in 238 HL patients. MiB1 (Ki-67) expression was evaluated in 211/238.
      RESULTS: The mean +/- SD percentage of topoIIalpha- and Ki-67-positive Hodgkin
      Reed-Sternberg (HRS) cells was 63 +/- 19% (5%-98%) and 73 +/- 19% (8%-99%),
      respectively. The median percentage of topoIIalpha-positive HRS cells was 64%
      (interquartile range, 51-78%). There was no correlation between topoIIalpha
      expression and patient characteristics. TopoIIalpha and Ki-67 expression were
      correlated (Spearman's Rho 0.255, P < 0.001). TopoIlalpha expression within the
      highest quartile of this patient population was predictive of failure free
      survival (FFS) (10-year rates 82 +/- 3% vs 68 +/- 7%, P = 0.02 for patients
      falling into the quartiles 1-3 and 4 respectively). In multivariate analysis
      topoIIalpha expression was independently predictive of FFS. CONCLUSION:
      TopoIIalpha was expressed in all cases of HL showing a correlation with Ki-67
      expression. Under current standard therapy including drugs inhibiting its
      activity, topoIIalpha was an independent adverse predictor of FFS with no
      statistically significant correlation with other established prognostic factors.

PMID- 18347179
TI  - Prognostic factors in renal cell carcinoma: association of preoperative sodium
      concentration with survival.
AB  - PURPOSE: Conventional renal cell carcinoma (RCC) has a variable natural history,
      and determining individual prognosis is important to guide management. We have
      examined the prognostic significance of a large number of hematologic and
      biochemical variables, as well as traditional tumor-related factors in patients
      with RCC. EXPERIMENTAL DESIGN: Patients undergoing nephrectomy for newly
      diagnosed RCC between September 1998 and March 2005 were invited to participate.
      Clinical, pathologic, and laboratory data were recorded in each case, and
      immunophenotyping was carried out on a subset of patients. A planned subset
      analysis of patients presenting with N0M0 disease was done. RESULTS: Two hundred
      twelve patients with RCC formed the study population. In addition to tumor
      related factors, multivariate analyses revealed preoperative serum sodium
      concentration to be independently and significantly associated with overall
      survival and disease-free survival when considered as both a continuous variable
      and when dichotomized to above and below the median value [139 mmol/L; reference
      range 135-145 mmol/L, hazard ratio 0.44, 95% confidence interval (95% CI) 0.22
      0.88, P = 0.014]. Five-year overall survival estimates for patients above and
      below the median serum sodium were 67.6% (95% CI 54.2-80.9) and 44.3% (95% CI
      32.8-55.8), respectively. These findings persisted in the N0M0 subgroup analysis.
      CONCLUSIONS: We have confirmed the prognostic value of traditional tumor-related
      factors but, to our knowledge, these are the first data to show that low
      preoperative sodium concentration may be an important factor associated with
      reduced survival in patients with RCC, suggesting that serum sodium should be
      considered with established prognostic variables in modeling survival in RCC.

PMID- 18347178
TI  - Cyclin D1 expression in breast cancer patients receiving adjuvant tamoxifen-based
      therapy.
AB  - PURPOSE: The objective of our study was to determine the clinical relevance of
      cyclin D1 expression in hormone receptor-positive breast cancer patients who were
      treated with tamoxifen-based therapy. EXPERIMENTAL DESIGN: We assessed expression
      of cyclin D1 in surgical specimens of breast carcinoma by means of
      immunohistochemistry. Patients had been enrolled in either Austrian Breast and
      Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received
      tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free
      survival were analyzed with Cox models adjusted for clinical and pathologic
      factors. RESULTS: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG
      Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin
      D1 was associated with poor outcome in both cohorts. Overall survival was
      significantly shorter in patients with cyclin D1-positive tumors compared with
      patients with cyclin D1-negative tumors [adjusted hazard ratio (HR) for death
      (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03;
      adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001].
      Relapse-free survival was also shorter in patients with cyclin D1-positive tumors
      than in patients with cyclin D1-negative tumors [adjusted HR for relapse (ABCSG
      Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG
      Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]. CONCLUSION: Cyclin D1 expression
      is an independent poor prognostic factor in women with early-stage, hormone
      receptor-positive breast cancer who received adjuvant tamoxifen-based therapy.

PMID- 18347180
TI  - Improving the quality of abstract reporting for phase I cancer trials.
AB  - PURPOSE: Conference abstracts of phase I trials (P1T) communicate important
      anticancer drug development information. Our objectives were to determine
      elements essential for good P1T abstract reporting, to assess the quality of P1T
      abstracts submitted to American Society of Clinical Oncology (ASCO) meetings, and
      to propose reporting guidelines. EXPERIMENTAL DESIGN: A survey of developmental
      therapeutics experts established elements of P1T reporting quality, and a scoring
      system was generated. All P1T abstracts published in ASCO Annual Proceedings from
      1997 to 2006 were reviewed, and the scoring system was applied. RESULTS: A survey
      was distributed twice to 69 experts, with a response rate of 39% (27 of 69).
      Experts rated 37 elements using a five-point scale, and elements with mean
      ratings over 3.75 were included in the final scoring system. One thousand six
      hundred and eighty three P1T abstracts were reviewed. A positive and linear
      association was observed between average expert rating of the elements and the
      proportion of P1T abstracts including those elements (Spearman correlation
      coefficient, rho = 0.60, P < 0.001). The median for all 1,683 abstracts was 62.5%
      (range, 25-95%; SD, 12.3%). Year of presentation was found to be significantly
      associated with higher quality scores (rho = 0.20, P < 0.001), with later years
      possessing better quality scores. The quality score was statistically significant
      as a predictor of type of presentation (odds ratio, 1.10; 95% confidence
      interval, 1.02-1.19 per 10% increase; P = 0.014), with oral presentations having
      the highest scores. CONCLUSIONS: The quality of P1T abstract reporting at ASCO
      has improved over time, although there is room for optimization. The quality of
      P1T abstract reporting may be enhanced using guidelines derived from our expert
      consensus.

PMID- 18347181
TI  - Irinotecan pharmacogenetics: influence of pharmacodynamic genes.
AB  - PURPOSE: Irinotecan is an important drug for the treatment of solid tumors.
      Although genes involved in irinotecan pharmacokinetics have been shown to
      influence toxicity, there are no data on pharmacodynamic genes. CDC45L, NFKB1,
      PARP1, TDP1, and XRCC1 have been shown to influence the cytotoxic action of
      camptothecins, including irinotecan. Polymorphisms in the drug target of
      camptothecins, topoisomerase I (TOP1), and downstream effectors may influence
      patient outcomes to irinotecan therapy. We undertook a retrospective candidate
      gene haplotype association study to investigate this hypothesis. EXPERIMENTAL
      DESIGN: Haplotype compositions of six candidate genes were constructed in
      European (n = 93), East Asian (n = 94), and West African (n = 95) populations.
      Haplotype-tagging single nucleotide polymorphisms (htSNP) were selected based on
      genealogic relationships between haplotypes. DNA samples from 107 European,
      advanced colorectal cancer patients treated with irinotecan-based regimens were
      genotyped for htSNPs as well as three coding region SNPs. Associations between
      genetic variants and toxicity (grade 3/4 diarrhea and neutropenia) or efficacy
      (objective response) were assessed. RESULTS: TOP1 and TDP1 htSNPs were related to
      grade 3/4 neutropenia (P = 0.04) and response (P = 0.04), respectively. Patients
      homozygous for an XRCC1 haplotype (GGCC-G) were more likely to show an objective
      response to therapy than other patients (83% versus 30%; P = 0.02). This effect
      was also seen in a multivariate analysis (odds ratio, 11.9; P = 0.04). No genetic
      variants were associated with diarrhea. CONCLUSIONS: This is the first
      comprehensive pharmacogenetic investigation of irinotecan pharmacodynamic
      factors, and our findings suggest that genetic variation in the pharmacodynamic
      genes may influence the efficacy of irinotecan-containing therapies in advanced
      colorectal cancer patients.

PMID- 18347182
TI  - Correlation of CDA, ERCC1, and XPD polymorphisms with response and survival in
      gemcitabine/cisplatin-treated advanced non-small cell lung cancer patients.
AB  - PURPOSE: Selecting patients according to key genetic characteristics may help to
      tailor chemotherapy and optimize the treatment in non-small cell lung cancer
      (NSCLC). Polymorphisms at the xeroderma pigmentosum group D (XPD), excision
      repair cross-complementing 1 (ERCC1), and cytidine deaminase (CDA) genes have
      been associated with alterations in enzymatic activity and may change sensitivity
      to the widely used cisplatin-gemcitabine regimen. EXPERIMENTAL DESIGN: Analyses
      of CDA, XPD, and ERCC1 polymorphisms were done on blood samples of 65
      chemotherapy-naive, advanced NSCLC patients treated with cisplatin-gemcitabine.
      Furthermore, CDA enzymatic activity was evaluated by high-performance liquid
      chromatography analysis. Association between XPD Asp(312)Asn and Lys(751)Gln,
      ERCC1 C118T, and CDA Lys(27)Gln polymorphisms and response, clinical benefit,
      toxicity, time to progression (TTP), and overall survival (OS) was estimated
      using Pearson's chi(2) tests, the Kaplan-Meier method, the log-rank test, and the
      Cox proportional hazards model. RESULTS: The CDA Lys(27)Lys polymorphism
      significantly correlated with better clinical benefit (P = 0.04) and grade > or
      =3 neutropenia and thrombocytopenia, as well as with longer TTP and OS (P = 0.006
      and P = 0.002, respectively), whereas no significant associations were found
      among ERCC1 and XPD polymorphisms and both response and clinical outcome.
      Finally, the enzymatic activity assay showed a significant lower mean in subjects
      harboring the CDA Lys(27)Lys polymorphism. CONCLUSIONS: Our data suggested the
      role of CDA Lys(27)Lys polymorphism as a possible predictive marker of activity,
      toxicity, TTP, and OS in advanced NSCLC patients treated with cisplatin and
      gemcitabine. These results may be explained by the lower enzymatic activity
      associated with the Lys(27)Lys CDA and offer a potential new tool for treatment
      optimization.

PMID- 18347183
TI  - Targeting hyaluronan interactions in malignant gliomas and their drug-resistant
      multipotent progenitors.
AB  - PURPOSE: To determine if hyaluronan oligomers (o-HA) antagonize the malignant
      properties of glioma cells and treatment-resistant glioma side population (SP)
      cells in vitro and in vivo. EXPERIMENTAL DESIGN: A single intratumoral injection
      of o-HA was given to rats bearing spinal cord gliomas 7 days after engraftment of
      C6 glioma cells. At 14 days, spinal cords were evaluated for tumor size, invasive
      patterns, proliferation, apoptosis, activation of Akt, and BCRP expression. C6SP
      were isolated by fluorescence-activated cell sorting and tested for the effects
      of o-HA on BCRP expression, activation of Akt and epidermal growth factor
      receptor, drug resistance, and glioma growth in vivo. RESULTS: o-HA treatment
      decreased tumor cell proliferation, increased apoptosis, and down-regulated
      activation of Akt and the expression of BCRP. o-HA treatment of C6SP inhibited
      activation of epidermal growth factor receptor and Akt, decreased BCRP
      expression, and increased methotrexate cytotoxicity. In vivo, o-HA also
      suppressed the growth of gliomas that formed after engraftment of C6 or BCRP+
      C6SP cells, although most C6SP cells lost their expression of BCRP when grown in
      vivo. Interestingly, the spinal cord gliomas contained many BCRP+ cells that were
      not C6 or C6SP cells but that expressed nestin and/or CD45; o-HA treatment
      significantly decreased the recruitment of these BCRP+ progenitor cells into the
      engrafted gliomas. CONCLUSIONS: o-HA suppress glioma growth in vivo by enhancing
      apoptosis, down-regulating key cell survival mechanisms, and possibly by
      decreasing recruitment of host-derived BCRP+ progenitor cells. Thus, o-HA hold
      promise as a new biological therapy to inhibit HA-mediated malignant mechanisms
      in glioma cells and treatment-resistant glioma stem cells.

PMID- 18347184
TI  - Antimyeloma effects of a sesquiterpene lactone parthenolide.
AB  - PURPOSE: Nuclear factor-kappaB (NF-kappaB), activated in multiple myeloma (MM)
      cells by microenvironmental cues, confers resistance to apoptosis. The
      sesquiterpene lactone parthenolide targets NF-kappaB. However, its therapeutic
      potential in MM is not known. EXPERIMENTAL DESIGNS: We explored the effects of
      parthenolide on MM cells in the context of the bone marrow microenvironment.
      RESULTS: Parthenolide inhibited growth of MM cells lines, including drug
      resistant cell lines, and primary cells in a dose-dependent manner. Parthenolide
      overcame the proliferative effects of cytokines interleukin-6 and insulin-like
      growth factor I, whereas the adhesion of MM cells to bone marrow stromal cells
      partially protected MM cells against parthenolide effect. In addition,
      parthenolide blocked interleukin-6 secretion from bone marrow stromal cells
      triggered by the adhesion of MM cells. Parthenolide cytotoxicity is both caspase
      dependent and caspase-independent. Parthenolide rapidly induced caspase
      activation and cleavage of PARP, MCL-1, X-linked inhibitor of apoptosis protein,
      and BID. Parthenolide rapidly down-regulated cellular FADD-like IL-1beta
      converting enzyme inhibitory protein, and direct targeting of cellular FADD-like
      IL-1beta-converting enzyme inhibitory protein using small interfering RNA
      oligonucleotides inhibited MM cell growth and lowered the parthenolide
      concentration required for growth inhibition. An additive effect and synergy were
      observed when parthenolide was combined with dexamethasone and TNF-related
      apoptosis-inducing ligand, respectively. CONCLUSION: Collectively, parthenolide
      has multifaceted antitumor effects toward both MM cells and the bone marrow
      microenvironment. Our data support the clinical development of parthenolide in MM
      therapy.

PMID- 18347185
TI  - Cytotoxicity and proteomics analyses of OSU03013 in lung cancer.
AB  - PURPOSE: Most lung cancer patients have some resistance to and suffer from side
      effects of conventional chemotherapy. Thus, identification of a novel anticancer
      drug with better target selectivity for lung cancer treatment is urgently needed.
      EXPERIMENTAL DESIGN: In order to investigate whether OSU03013, a derivative of
      celecoxib, can be a potential drug for lung cancer treatment, we examined its
      cytotoxicity mechanisms by flow cytometry and phosphatidylserine staining in
      A549, CL1-1, and H1435 lung cancer cell lines, which are resistant to the
      conventional drug, cisplatin. In addition, we identified the affected proteins by
      proteomics and confirmed the selected proteins by Western blot analysis. We
      examined the interaction between OSU03013 and potential target protein by
      molecular modeling. RESULTS: Our results indicated that OSU03013 had low-dose (1
      approximately 4 microM) cytotoxicity in all lung cancer cell lines tested 48
      hours posttreatment. OSU03013 caused cell cycle G1 phase arrest and showed
      phosphatidylserine early apoptosis via endoplasmic reticulum stress. Several
      proteins such as heat shock protein 27, 70, and 90, CDC2, alpha-tubulin, annexin
      A3, cAMP-dependent protein kinase, glycogen synthase kinase 3-beta, and beta
      catenin were identified by proteomics and confirmed by Western blot. In addition,
      molecular modeling showed that OSU03013 competes with ATP to bind to cAMP
      dependent protein kinase. CONCLUSIONS: We identified for the first time that
      OSU03013 inhibits cAMP-dependent protein kinase activity and causes
      dephosphorylation of glycogen synthase kinase 3-beta leading to beta-catenin
      degradation, which is often overexpressed in lung cancer. Our molecular and
      proteomic results show the potential of OSU03013 as an anticancer drug for lung
      cancer.

PMID- 18347186
TI  - Synergistic antipancreatic tumor effect by simultaneously targeting hypoxic
      cancer cells with HSP90 inhibitor and glycolysis inhibitor.
AB  - PURPOSE: We sought to examine the synergistic antipancreatic cancer effect by
      simultaneously targeting hypoxic cancer cells with heat-shock protein 90 (HSP90)
      inhibitor and blockade of energy production. EXPERIMENTAL DESIGN: The anticancer
      effects of an HSP90 inhibitor (geldanamycin) in pancreatic cells were
      investigated in hypoxia and normoxia. A hexokinase II inhibitor, 3-broma-pyruvate
      (3BrPA), was evaluated for selective glycolysis inhibition in hypoxia as a
      sensitizer of HSP90 inhibitor against pancreatic cancer. The HSP90 client protein
      degradation was monitored by Western blot. The synergistic antitumor effect of
      geldanamycin and 3BrPA was evaluated in a xenograft pancreatic cancer model and
      monitored by a noninvasive dynamic contrast-enhanced magnetic resonance imaging.
      RESULTS: Hypoxia enhanced HIF-1alpha expression by 11-fold in pancreatic cancer
      cells, and HSP90 inhibitor exhibited a seven- to eightfold higher anticancer
      effect in hypoxia compared with normoxia via HSP90 client protein degradation.
      3BrPA selectively inhibited glycolysis and sensitized geldanamycin against
      pancreatic cancer cells by 17- to 400-fold through HSP90 client protein
      degradation. The synergistic anticancer effect of reduced doses of geldanamycin
      and 3-BrPA was confirmed in xenograft models in vivo by more than 75% tumor
      growth inhibition. CONCLUSIONS: The combination of HSP90 inhibitors and
      glycolysis inhibitors provides preferential inhibition of cancer cells in hypoxia
      through HSP90 client protein degradation and selective glycolysis inhibition.
      This may provide a new therapeutic regimen to battle chemotherapy-resistant
      pancreatic cancers, by enhancing the synergistic therapeutic efficacy and
      reducing dose-limiting toxicity.

PMID- 18347187
TI  - Vitamin E succinate induces ceramide-mediated apoptosis in head and neck squamous
      cell carcinoma in vitro and in vivo.
AB  - PURPOSE: Vitamin E succinate (alpha-TOS) inhibits the growth of cancer cells
      without unacceptable side effects. Therefore, the mechanisms associated with the
      anticancer action of alpha-TOS, including ceramide-mediated apoptosis, were
      investigated using head and neck squamous cell carcinoma (HNSCC) in vitro and in
      vivo. EXPERIMENTAL DESIGN: Five different human HNSCC cell lines (JHU-011, JHU
      013, JHU-019, JHU-022, and JHU-029) were treated with alpha-TOS, and its effects
      on cell proliferation, cell cycle progression, ceramide-mediated apoptosis, and
      ceramide metabolism were evaluated. The anticancer effect of alpha-TOS was also
      examined on JHU-022 solid tumor xenograft growth in immunodeficient mice.
      RESULTS: Alpha-TOS inhibited the growth of all the HNSCC cell lines in vitro in a
      dose- and time-dependent manner. Thus, JHU-013 and JHU-022 cell lines were more
      sensitive to alpha-TOS than the other cell lines. Cellular levels of ceramide,
      sphingomyelinase activity, caspase-3, and p53 were elevated with increasing time
      of exposure to alpha-TOS. The degradation of poly(ADP-ribose) polymerase protein
      in JHU-022 cells treated with alpha-TOS provided evidence for apoptosis. The
      amounts of nuclear factor kappaB, Bcl-2, and Bcl-X(L) proteins were reduced in
      the cells treated with alpha-TOS for 6 hours. The levels of caspase-9, murine
      double minute-2, and IkappaB-alpha proteins were unchanged after alpha-TOS
      treatment. I.p. administration of alpha-TOS slowed tumor growth in
      immunodeficient mice. CONCLUSIONS: Alpha-TOS showed promising anticancer effects
      to inhibit HNSCC growth and viability in vivo and in vitro. The induction of
      enzymes involved in ceramide metabolism by alpha-TOS suggests that ceramide
      mediated apoptosis may expand therapeutic strategies in the treatment of
      carcinoma.

PMID- 18347188
TI  - Resveratrol exerts antiproliferative activity and induces apoptosis in
      Waldenstrom's macroglobulinemia.
AB  - PURPOSE: Resveratrol (3,4',5-tri-hydroxy-trans-stilbene) is an antioxidant
      constituent of a wide variety of plant species including grapes. It has gained
      considerable attention because of its anticancer properties, as shown in solid
      and hematologic malignancies. Whether resveratrol could inhibit proliferation or
      induce cytotoxicity in Waldenstrom's macroglobulinemia (WM) was investigated.
      EXPERIMENTAL DESIGN: We studied resveratrol-induced inhibition of proliferation
      and induction of cytotoxicity in WM cell lines, WM primary tumor cells, IgM
      secreting cells, and peripheral blood mononuclear cells. The mechanisms of action
      and different signaling pathways involved were studied using Western blot and
      gene expression profile analysis. Resveratrol activity was also evaluated in the
      bone marrow microenvironment. We finally investigated whether or not resveratrol
      could have any synergistic effect if used in combination with other drugs widely
      used in the treatment of WM. RESULTS: A schematic image illustrating the location
      and expression of the aurora kinases A, B, and C during mitosis. Resveratrol
      inhibited proliferation and induced cytotoxicity against WM cells, IgM-secreting
      cells, as well as primary WM cells, without affecting peripheral blood
      mononuclear cells; down-regulated Akt, extracellular signal-regulated kinase
      mitogen-activated protein kinases, and Wnt signaling pathways, as well as Akt
      activity; induced cell cycle arrest and apoptosis; and triggered c-Jun-NH(2)
      terminal-kinase activation, followed by the activation of intrinsic and extrinsic
      caspase pathways. Lastly, adherence to bone marrow stromal cells did not confer
      protection to WM cells against resveratrol-induced cytotoxicity. Furthermore,
      resveratrol showed synergistic cytotoxicity when combined with dexamethasone,
      fludarabine, and bortezomib. CONCLUSION: Our data show that resveratrol has
      significant antitumor activity in WM, providing the framework for clinical trials
      in this disease.

PMID- 18347189
TI  - Radiation enhances adenoviral gene therapy in pancreatic cancer via activation of
      cytomegalovirus promoter and increased adenovirus uptake.
AB  - PURPOSE: Adenovirus-mediated gene therapy combined with radiation is expected to
      be a new approach to treat pancreatic cancer. However, there are no reports of
      definitive effects of radiation on adenovirus-mediated gene therapies. In the
      present study, we investigated the effect of radiation on the transduction
      efficiency of an adenovirus-based gene therapy. EXPERIMENTAL DESIGN: We used
      adenovirus expressing NK4 (Ad-NK4), an antagonist for hepatocyte growth factor,
      as a representative gene therapy. Pancreatic cancer cells preinfected with Ad-NK4
      were irradiated, and NK4 levels in culture media of these cells were measured. We
      investigated cytomegalovirus (CMV) promoter activity and uptake of adenovirus in
      these cells. To examine the effect of radiation in vivo, Ad-NK4 was given to
      irradiated subcutaneous tumors in nude mice, and NK4 levels in tumors were
      measured. RESULTS: NK4 levels in culture media of irradiated cells were 4.5-fold
      (P < 0.01) higher than those of nonirradiated cells. Radiation enhanced
      activation of the CMV promoter and adenovirus uptake (P < 0.01), leading to
      increased levels of NK4. We found that activation of p38 mitogen-activated
      protein kinase and up-regulation of dynamin 2 may be involved in the radiation
      induced activation of the CMV promoter and adenovirus uptake, respectively. NK4
      levels in irradiated tumors were 5.8-fold (P = 0.017) higher than those in
      nonirradiated tumors. CONCLUSIONS: The present findings suggest that radiation
      significantly improves the efficiency of adenovirus-mediated gene transfer in
      pancreatic cancer and probably contributes to decreasing the dose of adenovirus
      required for gene transfer and controlling side effects of adenovirus infection
      in nonirradiated normal tissue.

PMID- 18347190
TI  - Inhibition of the tumor necrosis factor-alpha pathway is radioprotective for the
      lung.
AB  - PURPOSE: Radiation-induced lung toxicity limits the delivery of high-dose
      radiation to thoracic tumors. Here, we investigated the potential of inhibiting
      the tumor necrosis factor-alpha (TNF-alpha) pathway as a novel radioprotection
      strategy. EXPERIMENTAL DESIGN: Mouse lungs were irradiated with various doses and
      assessed at varying times for TNF-alpha production. Lung toxicity was measured by
      apoptosis and pulmonary function testing. TNF receptor 1 (TNFR1) inhibition,
      achieved by genetic knockout or antisense oligonucleotide (ASO) silencing, was
      tested for selective lung protection in a mouse lung metastasis model of colon
      cancer. RESULTS: Lung radiation induced local production of TNF-alpha by
      macrophages in BALB/c mice 3 to 24 hours after radiation (15 Gy). A similar
      maximal induction was found 1 week after the start of radiation when 15 Gy was
      divided into five daily fractions. Cell apoptosis in the lung, measured by
      terminal deoxyribonucleotide transferase-mediated nick-end labeling staining
      (mostly epithelial cells) and Western blot for caspase-3, was induced by
      radiation in a dose- and time-dependent manner. Specific ASO inhibited lung TNFR1
      expression and reduced radiation-induced apoptosis. Radiation decreased lung
      function in BALB/c and C57BL mice 4 to 8 weeks after completion of fractionated
      radiation (40 Gy). Inhibition of TNFR1 by genetic deficiency (C57BL mice) or
      therapeutic silencing with ASO (BALB/c mice) tended to preserve lung function
      without compromising lung tumor sensitivity to radiation. CONCLUSION: Radiation
      induced lung TNF-alpha production correlates with early cell apoptosis and latent
      lung function damage. Inhibition of lung TNFR1 is selectively radioprotective for
      the lung without compromising tumor response. These findings support the
      development of a novel radioprotection strategy using inhibition of the TNF-alpha
      pathway.

PMID- 18347191
TI  - Ataxia telangiectasia mutated and p21CIP1 modulate cell survival of drug-induced
      senescent tumor cells: implications for chemotherapy.
AB  - PURPOSE: Premature or stress-induced senescence is a major cellular response to
      chemotherapy in solid tumors and contributes to successful treatment. However,
      senescent tumor cells are resistant to apoptosis and may also reenter the cell
      cycle. We set out to find a means to specifically induce senescent tumor cells to
      undergo cell death and not to reenter the cell cycle that may have general
      application in cancer therapy. EXPERIMENTAL DESIGN: We investigated the
      mechanisms regulating cell survival in drug-induced senescent tumor cells. Using
      immunofluorescence and flow cytometry-based techniques, we established the status
      of the ataxia telangiectasia mutated (ATM) signaling pathway in these cells. We
      assayed the requirement of ATM signaling and p21(CIP1) expression for survival in
      premature senescent tumor cells using pharmacologic inhibitors and antisense
      oligonucleotides. RESULTS: The ATM/ATR (ATM- and Rad3-related) signaling pathway
      was found to be constitutively active in drug-induced senescent tumor cells. We
      found that blocking ATM/ATR signaling with pharmacologic inhibitors, including
      the novel ATM inhibitors KU55933 and CGK733, induced senescent breast, lung, and
      colon carcinoma cells to undergo cell death. We show that the mechanism of action
      of this effect is directly via p21(CIP1), which acts downstream of ATM. This is
      in contrast to the effects of ATM inhibitors on normal, untransformed senescent
      cells. CONCLUSIONS: Blocking ATM and/or p21(CIP1) following initial treatment
      with a low dose of senescence-inducing chemotherapy is a potentially less toxic
      and highly specific treatment for carcinomas.

PMID- 18347192
TI  - Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a
      camptothecin-11-refractory model.
AB  - PURPOSE: Clinical development of SN38, the active metabolite of camptothecin-11
      (CPT-11), has been hampered due to its poor solubility. We have developed a novel
      polymer-drug conjugate, EZN-2208, made by linking SN38 with a multiarm
      polyethylene glycol via a glycine linker. EXPERIMENTAL DESIGN: The in vitro
      cytotoxicity of EZN-2208 was tested using the 3-(4,5-dimethylthiazol-2-yl)-5-(3
      carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. The therapeutic
      efficacy of EZN-2208 was evaluated in various xenografts, including an in vivo
      selected CPT-11-refractory model. Tumor and blood concentration of EZN-2208, CPT
      11, and SN38 was determined by high-performance liquid chromatography. RESULTS:
      In vitro, EZN-2208 was 10- to 245-fold more potent than CPT-11 in a panel of
      human tumor cell lines. In xenograft models of MX-1 breast, MiaPaCa-2 pancreatic,
      or HT-29 colon carcinoma, treatment with either a single dose or multiple
      injections of EZN-2208 was more efficacious (and in some cases produced tumor
      eradication for >16 weeks) compared with CPT-11 at their respective maximum
      tolerated doses or corresponding dose levels (P < 0.01). Most interestingly, EZN
      2208 showed marked antitumor activity in animals that developed resistance to an
      8-day course of CPT-11 treatment, as well as outperformed CPT-11 as second-round
      therapy in mice initially sensitive to CPT-11. EZN-2208 had prolonged circulation
      in the blood compared with CPT-11, resulting in high tumor exposure. This
      resulted in higher and longer-lasting tumor exposure of free SN38 in mice given
      EZN-2208 compared with those given CPT-11. CONCLUSIONS: Preclinical data suggest
      that EZN-2208 may be a promising anticancer agent in a wide variety of clinical
      settings, including tumors refractory to CPT-11 treatment.

PMID- 18347193
TI  - Sensitivity of squamous cell carcinoma lymph node metastases to herpes oncolytic
      therapy.
AB  - PURPOSE: Cancer metastases may have phenotypic and genetic differences from their
      primary cancers of origin. Engineered, replication-competent, attenuated viruses
      based on herpes simplex virus-1 (HSV-1) have shown potent oncolytic effects in
      treating primary tumors in animal tumor models, but their efficacy in treating
      lymph node metastases is poorly understood. We compared the efficacy of an
      attenuated oncolytic HSV-1 (NV1023) in treating a series of murine squamous
      carcinoma cell lines derived from serial implantation and harvest from metastatic
      lymph nodes. EXPERIMENTAL DESIGN AND RESULTS: The auricles of C3H/HeJ mice were
      implanted with SCCVII. Cervical nodal metastases were isolated, expanded in
      vitro, and reimplanted into new mice. A series of cell lines (LN1-LN7) were
      generated through seven serial passages. Cells from higher LN passages showed
      consistent trends toward increased migratory and invasive ability, increased cell
      surface nectin-1 (an HSV-1 receptor) expression, and increased glycoprotein D
      binding. Exposure to NV1023 showed increased viral entry, replication, and
      cytotoxicity with higher LN passages. Intratumoral injection of NV1023 in a
      murine flank tumor model caused significantly greater tumor regression and
      increased viral infection of LN7 compared with SCCVII. CONCLUSIONS: These results
      show that lymph node metastases may undergo selection for characteristics,
      including increased nectin-1 expression, that make them more sensitive targets
      for herpes oncolytic therapy. These findings support the clinical application of
      these agents for the treatment of lymph node metastases.

PMID- 18347194
TI  - Toll-like receptor 4 mediates an antitumor host response induced by Salmonella
      choleraesuis.
AB  - PURPOSE: We have shown tumor-targeting and antitumor activities of an attenuated
      Salmonella choleraesuis in various tumor models. Meanwhile, host factors,
      including innate and adaptive immune responses, play roles in Salmonella-induced
      antitumor activity. Toll-like receptor 4 (TLR4) is identified as a signaling
      receptor for lipopolysaccharide derived from Gram-negative bacteria. However, the
      detailed mechanism of the S. choleraesuis-induced antitumor immune response via
      TLR4 remained uncertain. EXPERIMENTAL DESIGN: Herein, we used wild-type C3H/HeN
      mice and TLR4-deficient C3H/HeJ mice to study the role of TLR4 in the antitumor
      immune responses induced by S. choleraesuis. RESULTS: The amounts of S.
      choleraesuis were cleared more rapidly from the normal organs in C3H/HeN mice
      than those in C3H/HeJ mice. Tumors in C3H/HeN mice treated with S. choleraesuis
      were significantly smaller than those treated with PBS. By contrast, in TLR4
      deficient mice, there was a slight difference in inhibition of tumor growth.
      Meanwhile, we found that S. choleraesuis significantly up-regulated IFN-gamma,
      IFN-inducible chemokines CXCL9 (MIG), and CXCL10 (IP-10) productions in C3H/HeN
      mice, but not in C3H/HeJ mice. Furthermore, immunohistochemical staining of the
      tumors revealed less intratumoral microvessel density, more infiltration of
      macrophages, neutrophils, CD4(+) and CD8(+) T cells, and cell death in C3H/HeN
      mice after S. choleraesuis treatment compared with those in C3H/HeJ mice. The
      interaction between TLR4 and S. choleraesuis seemed to polarize the T-cell
      response to a T helper 1-dominant state. CONCLUSIONS: These results suggest TLR4
      may play an important role in the molecular mechanism of S. choleraesuis-induced
      host antitumor responses.

PMID- 18347195
TI  - Molecular alterations in spontaneous sputum of cancer-free heavy smokers: results
      from a large screening program.
AB  - PURPOSE: The high mortality rate for lung cancer is likely to be reduced by the
      development of a panel of sensitive biological markers able to identify early
      stage lung cancers or subjects at high risk. The aim of this study was to
      establish the frequency of K-ras and p53 mutations and p16(INK4A), RASSF1A, and
      NORE1A hypermethylation in sputum of a large cohort of cancer-free heavy smokers
      and to assess whether these markers are suitable for a routine use in the
      clinical practice for the early diagnosis of pulmonary cancer. EXPERIMENTAL
      DESIGN: Sputum samples were collected from 820 heavy smokers. Inclusion criteria
      consisted of radiologic and cytologic absence of pulmonary lesions, age at least
      60 years, male gender, and a smoking history of at least 20 pack-years. RESULTS:
      The analysis identified 56 individuals (6.9%) with one molecular alteration. p53
      mutation and p16(INK4A), RASSF1A, and NORE1A methylation frequencies were 1.9%,
      5.1%, 0.8%, and 1.0%, respectively; no K-ras mutations were found. One patient
      with p53 mutations was diagnosed with an early-stage lung cancer after 3-years of
      follow-up. The molecular analysis of bronchoscopy samples confirmed in half of
      the cases alterations present in sputum without revealing additional molecular
      changes. CONCLUSIONS: Genetic and epigenetic abnormalities can be detected in
      cancer-free heavy smokers. Although the predictive value of the cancer risk is
      still to be established as it requires not less than 5 years of follow-up, p53
      and p16(INK4A) are more promising candidates than K-ras, RASSF1A, and NORE1A for
      the pulmonary molecular screening of heavy smokers healthy individuals.

PMID- 18347197
TI  - Does erythropoietin promote tumor growth?

PMID- 18347199
TI  - The influence of collaboration on program outcomes: the Colorado Nurse-Family
      Partnership.
AB  - Though collaboration is often required in community initiatives, little evidence
      documents relationships between collaboration and program success. The authors
      contend that clarification of the construct collaboration is necessary for
      investigating its contribution to the success of community initiatives. After
      respecifying collaboration, they present a study of a multisite program that
      involved varying degrees of collaboration in the 16 communities adopting a nurse
      home visitation program. The authors employ hierarchical linear modeling (HLM) to
      test the predictive power of individual participant characteristics and examine
      the increased accuracy of predictions from a second level model of site qualities
      -specifically, features of the collaborative process associated with different
      sites. The first-level model predicted approximately 10% of the variance in
      attrition, or dropout, of program clients. The second-level model accounted for
      an additional 28% of the variance in attrition. A theory of commitment transfer
      is offered as a first explanation of this result.

PMID- 18347198
TI  - Scavenging roles of chemokine receptors: chemokine receptor deficiency is
      associated with increased levels of ligand in circulation and tissues.
AB  - In vitro studies have implicated chemokine receptors in consumption and clearance
      of specific ligands. We studied the role that various signaling chemokine
      receptors play during ligand homeostasis in vivo. We examined the levels of
      ligands in serum and CNS tissue in mice lacking chemokine receptors. Compared
      with receptor-sufficient controls, Cx3cr1(-/-) mice exhibited augmented levels of
      CX3CL1 both in serum and brain, and circulating levels of CXCL1 and CXCL2 were
      increased in Cxcr2(-/-) mice. CCR2-deficient mice showed significantly increased
      amounts of circulating CCL2 compared with wild-type mice. Cxcr3(-/-) mice
      revealed increased levels of circulating and brain CXCL10 after experimental
      autoimmune encephalomyelitis (EAE) induction. CCR2-deficient peripheral blood and
      resident peritoneal cells exhibited reduced binding capacity and biologic
      responses to the CCR1 ligand CCL3, suggesting that elevated levels of CCR2
      ligands had down-regulated CCR1. The results indicate that signaling chemokine
      receptors clear chemokines from circulation and tissues. These homeostatic
      functions of signaling chemokine receptors need to be integrated into safety and
      efficacy calculations when considering therapeutic receptor blockade.

PMID- 18347200
TI  - Using tax parcels to select a location-based sample: an illustration that
      examines residents' awareness of sex offenders in neighborhoods.
AB  - Social science research is increasingly considering place when examining social
      programs and policies with a spatial component. A specific research challenge
      involving spatial policies is how to select a sample of individuals based on
      their geographic locations. This article illustrates the use of geographic
      information systems, tax parcels, and mail surveys to target residents in varied
      geographic areas. A provided example demonstrates how researchers obtained a
      sample of respondents living within one tenth of a mile of multiple registered
      sex offenders. The challenges of using tax parcels to obtain addresses for
      apartments and mobile home parks are also explored.

PMID- 18347201
TI  - Geographic variation of spirometry use in newly diagnosed COPD.
AB  - BACKGROUND: Studies indicate that not all physicians in clinical practice use
      spirometry routinely in the diagnosis of COPD. Understanding the patterns of
      spirometry use across geographic regions in patients with newly diagnosed COPD
      may help to identify the factors associated with the use of spirometry and to
      improve the quality of COPD care. The objective of this study was to characterize
      the regional variation in spirometry use for patients with newly diagnosed COPD
      using the Healthcare Effectiveness Data and Information Set (HEDIS) 2006
      spirometry performance measure. METHODS: We identified patients within the
      Veteran Health Administration who were >42 years of age who had received a new
      diagnosis of COPD between July 2003 and June 2004. The date of the COPD diagnosis
      was the index date. Spirometry use from 760 days prior to the index date to 180
      days after the index date was identified. The Veterans Integrated Service
      Networks (VISNs) was used as the geographic unit for comparison. RESULTS: Of the
      93,724 patients included in the study, 36.7% underwent spirometry during the
      study period. Using the largest VISN as the referent, there was more than a
      threefold difference in the adjusted odds ratios (AORs) for spirometry use
      between the regions with the lowest use (AOR, 0.52; 95% confidence interval [CI],
      0.48 to 0.57) and the highest use (AOR, 1.61; 95% CI, 1.46 to 1.78). CONCLUSIONS:
      Overall, the use of spirometry in patients with newly diagnosed COPD was low
      using the new HEDIS spirometry measure with a significant regional variation
      comprising a more than threefold difference between the regions with the lowest
      and highest rates of spirometry use.

PMID- 18347202
TI  - Effects of continuous positive airway pressure treatment and withdrawal in
      patients with obstructive sleep apnea on arterial stiffness and central BP.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is associated with increased BP and
      other cardiometabolic risk factors. The aim of the present study was to determine
      whether arterial stiffness and central BP (two important cardiovascular risk
      factors) would change, independent of peripheral BP following either the
      initiation of or withdrawal from nasal continuous positive airway pressure (CPAP)
      treatment in subjects with OSA. METHODS AND RESULTS: Arterial stiffness and
      peripheral and central BP were measured at baseline, and then either at 2 months
      after starting CPAP therapy (intervention group, n=20) or 7 nights after
      withdrawal from CPAP therapy (withdrawal group, n=20) using pulse wave analysis.
      In the intervention group, there were reductions in arterial stiffness (ie, the
      aortic augmentation index fell by 2.5%) and central systolic BP (fell by 4.2 mm
      Hg) without a concomitant reduction in peripheral BP. The change in arterial
      stiffness was associated with CPAP compliance (r=-0.47). In contrast, in the
      withdrawal group there were no overall changes in arterial stiffness or BP.
      However, there was an early morning increase in diastolic BP and heart rate
      relative to late evening. CONCLUSION: These results suggest that clinically
      important changes in arterial stiffness and central BP may occur following
      effective CPAP treatment of OSA without parallel changes in peripheral BP.

PMID- 18347203
TI  - Effects of lung volume reduction surgery for emphysema on glycolipidic hormones.
AB  - BACKGROUND: Pulmonary emphysema is associated with cachexia and disregulation of
      the hormones regulating the glycolipid metabolism, insulin resistance, and
      altered substrate utilization. This study aimed at identifying the effects of
      lung volume reduction surgery (LVRS) on glycolipidic hormones compared to
      respiratory rehabilitation (RR). METHODS: Thirty-three patients with moderate-to
      severe emphysema who were undergoing video-assisted thoracoscopic LVRS were
      compared to 31 similar patients who refused the operation and followed a
      standardized RR program. All patients were evaluated before and 12 months after
      treatment for respiratory function, body composition, glycolipidic hormones,
      metabolic parameters, and insulin resistance, which was calculated using the
      homeostatic model assessment index for insulin resistance (HOMA-IR). These groups
      were compared to a matched healthy control population. RESULTS: Only after LVRS
      significant improvements were obtained in respiratory function (FEV1, +25.2%;
      p<0.0001; residual volume, -19.5%; p<0.0001), metabolic parameters (total
      cholesterol, +13.1%; p<0.01; high-density lipoprotein cholesterol, +11.2%;
      p<0.01; triglycerides, +18.4; p<0.001; nonesterified fatty acid, -19.7%;
      p<0.001), and body composition (fat-free mass [FFM], +6.5%; p<0.01; fat mass
      [FM], +11.9%; p<0.01). The leptin/FM ratio (-6.1%; p<0.01) and resistin/FM ratio
      (-5.6%; p<0.01) decreased, whereas the adiponectin/FM ratio (+6.9%; p<0.01) and
      ghrelin (+9.2%; p<0.01) increased, together with reductions in glycemia (-8.8%;
      p<0.01), insulin level (-20.4%; p<0.001), and HOMA-IR (-27.2%; p<0.0001). The
      decrement in residual volume was correlated with increment of FFM (rho=-0.49;
      p<0.02), FM (rho=-0.55; p<0.009), and ghrelin (rho=-0.52; p<0.01), and also with
      decreases in leptin corrected for FM (rho=0.50; p<0.02) and, marginally, HOMA-IR
      (rho=0.35; p=0.07). CONCLUSIONS: After LVRS, glycolipidic hormone levels and
      nutritional status significantly improved, along with insulin resistance
      reduction and more physiologic utilization of substrates. Correlations between
      residual volume and body composition as well as glycolipidic hormone levels
      suggest that postoperative recovery in respiratory dynamics may induce favorable
      clinical changes when compared to RR.

PMID- 18347204
TI  - Alterations during medical interpretation of ICU family conferences that
      interfere with or enhance communication.
AB  - RATIONALE: Many conferences in the ICU occur with the families of patients with
      limited English proficiency, requiring a medical interpreter. Despite the
      importance of medical interpretation, little is known about the alterations that
      occur and their effect on communication. OBJECTIVES: This study characterizes the
      types, prevalence, and potential effects of alterations in interpretation during
      ICU family conferences involving end-of-life discussions. METHODS: We identified
      ICU family conferences in two hospitals in which a medical interpreter was used.
      Ten conferences were audiotaped; 9 physicians led these conferences, and 70
      family members participated. Research interpreters different from those attending
      the conference translated the non-English language portions of the audiotaped
      conferences. We identified interpretation alterations, grouped them into four
      types, and categorized their potential effects on communication. RESULTS: For
      each interpreted exchange between clinicians and family, there was a 55% chance
      that an alteration would occur. These alterations included additions, omissions,
      substitutions, and editorializations. Over three quarters of alterations were
      judged to have potentially clinically significant consequences on the goals of
      the conference. Of the potentially significant alterations, 93% were likely to
      have a negative effect on communication; the remainder, a positive effect. The
      alterations with potentially negative effects included interference with the
      transfer of information, reduced emotional support, and reduced rapport. Those
      with potential positive effects included improvements in conveying information
      and emotional support. CONCLUSIONS: Alterations in medical interpretation seem to
      occur frequently and often have the potential for negative consequences on the
      common goals of the family conference. Further studies examining and addressing
      these alterations may help clinicians and interpreters to improve communication
      with family members during ICU family conferences.

PMID- 18347205
TI  - Sleep-disordered breathing and quality of life of railway drivers in Greece.
AB  - BACKGROUND: Sleep-disordered breathing (SDB) and especially obstructive sleep
      apnea (OSA) are associated with daytime sleepiness and an increased risk for
      motor vehicle crashes. Previous studies have assessed the prevalence of OSA among
      professional drivers, but no study so far has focused on railway drivers. The aim
      of this study was to assess the prevalence of SDB among Greek railway drivers,
      and correlate it with daytime sleepiness, quality of life, and symptoms. METHODS:
      The following three different questionnaires were anonymously answered by 226
      train drivers: a general questionnaire on their demographics and sleep habits;
      the Greek version of the Epworth sleepiness scale (ESS); and the Medical Outcomes
      Study 36-item short form (SF-36). Of the 226 drivers, 50 underwent a sleep study,
      a physical examination, and an assessment of their respiratory function. RESULTS:
      Participants were all men, had a mean (+/-SD) age of 46.9+/-3.9 years, were
      overweight (mean body mass index [BMI], 28.7+/-3.7 kg/m2), and were smokers
      (59.7%). Snoring was reported by 69.9% of them, and apneas by 11.5%. The mean ESS
      score was 5.4+/-3.2. SF-36 scores were similar to those of the Greek population.
      The mean apnea-hypopnea index (AHI) was 11+/-14 events per hour, and the mean
      pulse oximetric saturation was 93.2+/-2.5%. According to AHI severity, they were
      divided into the following three groups: group 1, normal breathing function in
      sleep (n=19; AHI, <5 events per hour); group 2, mild OSA (n=20; AHI, 5.1 to 15
      events per hour); group 3, moderate/severe OSA (n=11; AHI, >15 events per hour).
      The three groups differed in terms of BMI, and neck, waist, and hip
      circumferences. No difference was detected, though, in ESS and SF-36 scores.
      CONCLUSION: The majority of the Greek railway drivers are overweight and smokers.
      The most common reported symptom in the questionnaires is snoring, without
      significant daytime impairment, while sleep studies show a potentially higher
      prevalence of OSA. TRIAL REGISTRATION: Democritus University of Thrace
      Identifier: 2979/5-2003. TRIAL REGISTRATION: Union of the Greek Railway Drivers
      Identifier: 536/10-2003.

PMID- 18347206
TI  - Complex molecular epidemiology of methicillin-resistant staphylococcus aureus
      isolates from children with cystic fibrosis in the era of epidemic community
      associated methicillin-resistant S aureus.
AB  - BACKGROUND: Limited data exist about the molecular types of methicillin-resistant
      Staphylococcus aureus (MRSA) strains found in children with cystic fibrosis (CF).
      We sought to characterize MRSA strains from these patients and compare them with
      MRSA strains from non-CF pediatric patients. METHODS: All MRSA isolates were
      collected prospectively at Children's Medical Center in Dallas, TX, and the
      University of Chicago Comer Children's Hospital in 2004 to 2005. All CF MRSA
      isolates underwent susceptibility testing, multilocus sequence typing, Panton
      Valentine leukocidin gene detection (pvl+), and staphylococcal chromosome
      cassette mec (SCCmec) typing. RESULTS: A total of 22 of 34 MRSA isolates (64.7%)
      from patients with CF belonged to clonal complex (CC) 5 and contained SCCmec II,
      so-called health-care associated MRSA (HA-MRSA) strains. Nine of 34 MRSA strains
      (26.5%) were CC 8, and contained SCCmec IV, so-called community-associated MRSA
      (CA-MRSA) strains. The CA-MRSA strains tended to be isolated from newly colonized
      CF patients. In contrast, CC8 isolates predominated among the non-CF patients
      (294 of 331 patients; 88.8%). MRSA isolates from children with CF were more
      likely to be resistant to clindamycin (65% vs 19%, respectively) and
      ciprofloxacin (62% vs 17%, respectively) compared with strains from non-CF
      patients (p < 0.001). There was no difference in the rate of pvl+ isolate
      recovery from children with CF undergoing a surveillance culture (7 of 23
      children) compared with those with pulmonary exacerbation (3 of 11 children; p =
      1.0). CONCLUSIONS: Both CA-MRSA (CC8) isolates and HA-MRSA (CC5) isolates
      populate the respiratory tracts of children with CF. HA-MRSA isolates
      predominated, but CA-MRSA strains predominated among CF patients with newly
      acquired MRSA strains and among the non-CF patients. The presence of CA-MRSA
      strains in children with CF was not associated with exacerbation or necrotizing
      pneumonia.

PMID- 18347207
TI  - The effect of previous tuberculin skin test on the follow-up examination of whole
      blood interferon-gamma assay in the screening for latent tuberculosis infection.
AB  - BACKGROUND: A two-step procedure using a tuberculin skin test (TST) followed by
      an interferon (IFN)-gamma assay in cases in which the TST result is positive has
      been advocated to screen for latent tuberculosis infection. However, TST could
      also boost the in vitro immune response. In this study, we evaluated the effect
      of TST on the results of the IFN-gamma assay. METHODS: Our study included 84
      health-care workers who had been working in the department of pulmonary medicine
      for > 1 year. First, a whole-blood IFN-gamma assay was performed, and then the
      TST was applied. Two to 4 weeks later, a follow-up IFN-gamma assay was performed.
      A commercially available IFN-gamma assay (QuantiFERON-TB GOLD; Cellestis Ltd;
      Carnegie, VIC, Australia) was used. RESULTS: Valid TST results were available in
      82 individuals because 2 participants refused to undergo the TST after the IFN
      gamma assay. The TST result was positive in 36 of 82 participants (42.7%), and
      the IFN-gamma assay was positive in 16 of 82 participants (19.5%). The overall
      agreement between the two tests was 67.5% (kappa = 0.31; 95% confidence interval,
      0.22 to 0.40). The IFN-gamma levels increased significantly from 0.05 to 0.19 (p
      = 0.011), and 3 of 18 participants (16.7%) had conversion of their IFN-gamma
      assay results in the TST-positive group. However, in the TST-negative group, the
      IFN-gamma levels did not change after the TST. CONCLUSION: The agreement between
      the results of the TST and the IFN-gamma assay was low, and IFN-gamma level could
      be influenced by the TST, in the TST-positive population, when a follow-up IFN
      gamma assay is performed 2 to 4 weeks later.

PMID- 18347208
TI  - A measure of ventilatory variability at wake-sleep transition predicts sleep
      apnea severity.
AB  - RATIONALE: Increased variability in ventilation may contribute to the
      pathogenesis of obstructive sleep apnea (OSA) by promoting ventilatory
      instability, fluctuations of neuromuscular output to the upper airway, and
      pharyngeal collapsibility. We assessed the association of a measure of
      ventilatory variability measured at the wake-sleep transition with OSA and
      associated covariates. METHODS: Four hundred eighty-five participants in the
      Cleveland Family Study underwent overnight polysomnography with independent
      derivation of the ventilatory variability index (VVI) and the apnea-hypopnea
      index (AHI). The VVI was calculated from the variability in the power spectrum of
      the abdominal inductance signal over a 2-min period beginning at sleep onset.
      RESULTS: The VVI was strongly correlated with the AHI (r=0.43; p<0.001). After
      adjusting for age, body mass index, sex, and race, the VVI remained significantly
      associated with AHI (p<0.001). The adjusted odds ratio for OSA (AHI, >or=15) with
      each half SD increase in VVI was 1.41 (range, 1.25 to 1.59). In a subgroup
      analysis of obese snorers, to limit analyses to those with a presumed anatomic
      predisposition for apnea, VVI remained associated with an elevated AHI.
      CONCLUSIONS: Increased ventilatory variability may be a useful phenotype in
      characterizing OSA.

PMID- 18347209
TI  - Microsomal prostaglandin E2 synthase-1 deletion leads to adverse left ventricular
      remodeling after myocardial infarction.
AB  - BACKGROUND: Pharmacological inhibition of cyclooxygenase-2 increases the risk of
      myocardial infarction (MI) and stroke. Microsomal prostaglandin (PG) E(2)
      synthase-1 (mPGES-1), encoded by the Ptges gene, functions downstream from
      cyclooxygenase-2 in the inducible PGE(2) biosynthetic pathway. We caused acute MI
      in Ptges(+/+) and Ptges(-/-) mice to define the role of mPGES-1 in cardiac
      ischemic injury. METHODS AND RESULTS: Twenty-eight days after MI, Ptges(-/-) mice
      develop more left ventricular (LV) dilation, have worse LV systolic and diastolic
      function, and have higher LV end-diastolic pressure than Ptges(+/+) mice but have
      similar pulmonary wet-to-dry weight ratios, cardiac mass, infarct size, and
      mortality. The length-to-width ratio of individual cardiomyocytes is
      significantly greater in Ptges(-/-) than Ptges(+/+) mice after MI, a finding
      consistent with eccentric cardiomyocyte hypertrophy in Ptges(-/-) mice.
      Expression of atrial natriuretic peptide, brain natriuretic peptide, and alpha-
      and beta-myosin heavy chain, markers of ventricular hypertrophy, is higher in the
      LV of Ptges(-/-) than Ptges(+/+) mice after MI. Ptges(+/+) mice express
      cyclooxygenase-2 and mPGES-1 protein in inflammatory cells adjacent to the
      infarct after MI but do not express these proteins in cardiomyocytes. Ptges(-/-)
      mice express cyclooxygenase-2 in inflammatory cells adjacent to the infarct and
      do not express mPGES-1 in any cells in the heart. Levels of PGE(2) but not
      PGD(2), thromboxane A(2), PGI(2), or PGF(2alpha) are higher in the infarct and LV
      remote from the infarct after MI in Ptges(+/+) than Ptges(-/-) mice. CONCLUSIONS:
      In Ptges(+/+) mice, mPGES-1 in inflammatory cells catalyzes PGE(2) biosynthesis
      in the LV after MI. Deletion of mPGES-1 leads to eccentric cardiac myocyte
      hypertrophy, LV dilation, and impaired LV contractile function after acute MI.

PMID- 18347210
TI  - Differential behaviors of atrial versus ventricular fibroblasts: a potential role
      for platelet-derived growth factor in atrial-ventricular remodeling differences.
AB  - BACKGROUND: In various heart disease paradigms, atria show stronger fibrotic
      responses than ventricles. The possibility that atrial and ventricular
      fibroblasts respond differentially to pathological stimuli has not been examined.
      METHODS AND RESULTS: We compared various morphological, secretory, and
      proliferative response indexes of canine atrial versus ventricular fibroblasts.
      Cultured atrial fibroblasts showed faster cell surface area increases, distinct
      morphology at confluence, and greater alpha-smooth muscle actin expression than
      ventricular fibroblasts. Atrial fibroblast proliferation ([(3)H]thymidine
      incorporation) responses were consistently greater for a range of growth factors,
      including fetal bovine serum, platelet-derived growth factor (PDGF), basic
      fibroblast growth factor, angiotensin II, endothelin-1, and transforming growth
      factor-beta(1). Normal atrial tissue showed larger myofibroblast density compared
      with ventricular tissue, and the difference was exaggerated by congestive heart
      failure. Congestive heart failure atria showed larger fractions of fibroblasts in
      mitotic phases compared with ventricles and displayed enhanced gene expression of
      fibroblast-selective markers (collagen-1, collagen-3, fibronectin-1). Gene
      microarrays revealed 225 differentially expressed transcript probe sets between
      paired atrial and ventricular fibroblast samples, including extracellular matrix
      (eg, fibronectin, laminin, fibulin), cell signaling (PDGF, PDGF receptor,
      angiopoietin, vascular endothelial growth factor), structure (keratin), and
      metabolism (xanthine dehydrogenase) genes, identifying PDGF as a candidate
      contributor to atrial-ventricular fibroblast differences. PDGF receptor gene
      expression was greater in normal atrium compared with ventricle, and congestive
      heart failure differentially enhanced atrial versus ventricular PDGF and PDGF
      receptor gene expression. PDGF receptor protein expression and alpha-smooth
      muscle actin protein expression were enhanced in isolated congestive heart
      failure fibroblasts. The PDGF receptor tyrosine kinase inhibitor AG1295
      eliminated fetal bovine serum- and transforming growth factor-beta(1)-stimulated
      atrial-ventricular fibroblast proliferative response differences. CONCLUSIONS:
      Atrial fibroblasts behave differently than ventricular fibroblasts over a range
      of in vitro and in vivo paradigms, with atrial fibroblasts showing enhanced
      reactivity that may explain greater atrial fibrotic responses. PDGF signaling is
      particularly important for atrium-selective fibroblast responses and may
      represent a novel target for arrhythmogenic atrial structural remodeling
      prevention.

PMID- 18347211
TI  - Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo)
      monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice.
AB  - BACKGROUND: Monocytes are critical mediators of atherogenesis. Deletion of
      individual chemokines or chemokine receptors leads to significant but only
      partial inhibition of lesion development, whereas deficiency in other signals
      such as CXCL16 or CCR1 accelerates atherosclerosis. Evidence that particular
      chemokine pathways may cooperate to promote monocyte accumulation into inflamed
      tissues, particularly atherosclerotic arteries, is still lacking. METHODS AND
      RESULTS: Here, we show that chemokine-mediated signals critically determine the
      frequency of monocytes in the blood and bone marrow under both noninflammatory
      and atherosclerotic conditions. Particularly, CCL2-, CX3CR1-, and CCR5-dependent
      signals differentially alter CD11b(+) Ly6G(-) 7/4(hi) (also known as Ly6C(hi))
      and CD11b(+) Ly6G(-) 7/4(lo) (Ly6C(lo)) monocytosis. Combined inhibition of CCL2,
      CX3CR1, and CCR5 in hypercholesterolemic, atherosclerosis-susceptible
      apolipoprotein E-deficient mice leads to abrogation of bone marrow monocytosis
      and to additive reduction in circulating monocytes despite persistent
      hypercholesterolemia. These effects are associated with a marked and additive 90%
      reduction in atherosclerosis. Interestingly, lesion size highly correlates with
      the number of circulating monocytes, particularly the CD11b(+) Ly6G(-) 7/4(lo)
      subset. CONCLUSIONS: CCL2, CX3CR1, and CCR5 play independent and additive roles
      in atherogenesis. Signals mediated through these pathways critically determine
      the frequency of circulating monocyte subsets and thereby account for almost all
      macrophage accumulation into atherosclerotic arteries.

PMID- 18347212
TI  - Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous
      thromboembolism: findings from the Registro Informatizado de la Enfermedad
      TromboEmbolica venosa (RIETE) Registry.
AB  - BACKGROUND: Clinical predictors for fatal pulmonary embolism (PE) in patients
      with venous thromboembolism have never been studied. METHODS AND RESULTS: Using
      data from the international prospective Registro Informatizado de la Enfermedad
      TromboEmbolica venosa (RIETE) registry about patients with objectively confirmed
      symptomatic acute venous thromboembolism, we determined independent predictive
      factors for fatal PE. Between March 2001 and July 2006, 15 520 consecutive
      patients (mean age+/-SD, 66.3+/-16.9 years; 49.7% men) with acute venous
      thromboembolism were included. Symptomatic deep-vein thrombosis without
      symptomatic PE was observed in 58.0% (n=9008) of patients, symptomatic nonmassive
      PE in 40.4% (n=6264), and symptomatic massive PE in 1.6% (n=248). At 3 months,
      the cumulative rates of overall mortality and fatal PE were 8.65% and 1.68%,
      respectively. On multivariable analysis, patients with symptomatic nonmassive PE
      at presentation exhibited a 5.42-fold higher risk of fatal PE compared with
      patients with deep-vein thrombosis without symptomatic PE (P<0.001). The risk of
      fatal PE was multiplied by 17.5 in patients presenting with a symptomatic massive
      PE. Other clinical factors independently associated with an increased risk of
      fatal PE were immobilization for neurological disease, age >75 years, and cancer.
      CONCLUSIONS: PE remains a potentially fatal disease. The clinical predictors
      identified in the present study should be included in any clinical risk
      stratification scheme to optimally adapt the treatment of PE to the risk of the
      fatal outcome.

PMID- 18347213
TI  - Prevalence of angina in women versus men: a systematic review and meta-analysis
      of international variations across 31 countries.
AB  - BACKGROUND: In the absence of previous international comparisons, we sought to
      systematically evaluate, across time and participant age, the sex ratio in angina
      prevalence in countries that differ widely in the rate of mortality due to
      myocardial infarction. METHODS AND RESULTS: We searched MEDLINE and EMBASE until
      February 2006 for healthy population studies published in any language that
      reported the prevalence of angina (Rose questionnaire) in women and men. We
      obtained myocardial infarction mortality rates from the World Health
      Organization. A total of 74 reports of 13,331 angina cases in women and 11,511
      cases in men from 31 countries were included. Angina prevalence varied widely
      across populations, from 0.73% to 14.4% (population weighted mean 6.7%) in women
      and from 0.76% to 15.1% (population weighted mean 5.7%) in men, and was strongly
      correlated within populations between the sexes (r=0.80, P<0.0001). Angina
      prevalence showed a small female excess with a pooled random-effects sex ratio of
      1.20 (95% CI 1.14 to 1.28, P<0.0001). This female excess was found across
      countries with widely differing myocardial infarction mortality rates in women
      (interquartile range 12.7 to 126.5 per 100,000), was particularly high in the
      American studies (1.40, 95% CI 1.28 to 1.52), and was higher among nonwhite
      ethnic groups than among whites. This sex ratio did not differ significantly by
      participant's age, the year the survey began, or the sex ratio for mortality due
      to myocardial infarction. CONCLUSIONS: Over time and at different ages,
      independent of diagnostic and treatment practices, women have a similar or
      slightly higher prevalence of angina than men across countries with widely
      differing myocardial infarction mortality rates.

PMID- 18347214
TI  - Management of cocaine-associated chest pain and myocardial infarction: a
      scientific statement from the American Heart Association Acute Cardiac Care
      Committee of the Council on Clinical Cardiology.

PMID- 18347215
TI  - Images in cardiovascular medicine. Papillary fibroelastoma of the tricuspid valve
      seen on magnetic resonance imaging.

PMID- 18347216
TI  - Letter by Tracey regarding article, "Bypassing big pharma".

PMID- 18347217
TI  - Letter by Naqvi and Motallebi regarding article, "Left ventricular
      resynchronization is mandatory for response to cardiac resynchronization
      therapy".

PMID- 18347219
TI  - Actively engaging patients in treatment decision making and monitoring as a
      strategy to improve hypertension outcomes in diabetes mellitus.

PMID- 18347220
TI  - Right ventricular function in cardiovascular disease, part I: Anatomy,
      physiology, aging, and functional assessment of the right ventricle.

PMID- 18347221
TI  - von Willebrand factor in cardiovascular disease: focus on acute coronary
      syndromes.
AB  - von Willebrand factor (VWF) plays a pivotal role in platelet adhesion and
      aggregation at sites of high shear rates (eg, in coronary arteries that have
      stenotic or ruptured atherosclerotic plaque lesions). Numerous studies have
      investigated the relationship between VWF plasma levels and thromboembolic
      cardiovascular events. In contrast to the rather weak association in the general
      population, in patients with preexisting vascular disease, VWF is significantly
      predictive for adverse cardiac events, including death. Likewise, VWF typically
      rises during the course of acute coronary syndrome, and the extent of this VWF
      release is an independent predictor of adverse clinical outcome in these
      patients. Various lines of evidence indicate that VWF is not only a marker but
      also actually an important effector in the pathogenesis of myocardial infarction.
      This central role of VWF in thrombogenesis has made it a promising target for
      research into new antiplatelet therapies that specifically inhibit VWF. This
      review focuses on the role of VWF in acute coronary syndrome and further outlines
      the relevance of therapeutic interventions targeting VWF for acute coronary
      syndrome patients.

PMID- 18347222
TI  - Endovascular management of thoracic dissections.

PMID- 18347223
TI  - Images in cardiovascular medicine. Optical mapping of the human atrioventricular
      junction.

PMID- 18347224
TI  - Vascular remodeling and duration of hypertension predict outcome of adrenalectomy
      in primary aldosteronism patients.
AB  - Remodeling of the resistance arteries is a hallmark of arterial hypertension and
      predicts cardiovascular events, but it was unknown whether it could also predict
      the blood pressure response to adrenalectomy of patients with an aldosterone
      producing adenoma. Therefore, we investigated the outcome of adrenalectomy as a
      function of vascular remodeling in the context of the preoperative features of
      aldosterone-producing adenoma patients. At 2 referral centers for hypertension,
      we prospectively measured the media:lumen ratio of small arteries from fat tissue
      of 50 consecutive aldosterone-producing adenoma patients treated with
      adrenalectomy. The blood pressure response to adrenalectomy was assessed by
      considering the blood pressure values and the number and dosages of
      antihypertensive medications. Adrenalectomy significantly (P<0.001) lowered
      plasma aldosterone (from 27.3+/-4.9 ng/dL to 8.3+/-11.2 ng/dL), the
      aldosterone:renin ratio (from 117+/-35 to 11+/-2), and blood pressure (from 163+/
      22/98+/-2 mm Hg to 133+/-2/84+/-1 mm Hg), even despite a reduction (from 141+/-14
      to 100+/-15; P=0.02) of the score of antihypertensive treatment. It provided cure
      of hypertension in 30% of the aldosterone-producing adenoma patients,
      normotension with less antihypertensive therapy in 52%, and improved blood
      pressure control in the rest. The media:lumen ratio and the known duration of
      hypertension significantly predicted the blood pressure response to adrenalectomy
      at univariate and multivariate analyses. Because a long duration of hypertension
      and/or the presence of vascular remodeling imply lower chances of blood pressure
      normalization at long-term follow-up postadrenalectomy, these findings emphasize
      the importance of an early diagnosis of aldosterone-producing adenoma.

PMID- 18347225
TI  - Critical review of prorenin and (pro)renin receptor research.

PMID- 18347226
TI  - The J-point revisited.

PMID- 18347227
TI  - Aldosterone and metabolic syndrome: is increased aldosterone in metabolic
      syndrome patients an additional risk factor?

PMID- 18347228
TI  - Angiotensin-converting enzyme inhibition after experimental myocardial infarct:
      role of the kinin B1 and B2 receptors.
AB  - We sought to define the contribution of each of the 2 kinin receptors (bradykinin
      1 receptor [B(1)R] and bradykinin 2 receptor [B(2)R]) to the cardioprotection of
      angiotensin-converting enzyme (ACE) inhibition after acute myocardial infarct.
      Wild-type mice and gene knockout mice missing either B(1)R or B(2)R were
      submitted to coronary ligation with or without concurrent ACE inhibition and had
      evaluation of left ventricular systolic capacity by assessment of fractional
      shortening (FS). Baseline FS was similar in all of the animals and remained
      unchanged in sham-operated ones. At 3 weeks after myocardial infarct, in the wild
      type group there was a 27% reduction of FS (P<0.5) without ACE inhibition and 8%
      with ACE inhibition; in the B(1)R(-/-) groups the FS was reduced by 24% and was
      no different (at 28%) with ACE inhibition; in the B(2)R(-/-) groups, however, the
      FS was decreased by 39% and with ACE inhibition was decreased further by 52%.
      Analysis of bradykinin receptor gene expression in hearts showed that when one
      receptor was missing, the other became significantly upregulated; but the B(1)R
      remained highly overexpressed in the B(2)R(-/-) mice throughout, whereas the
      overexpressed B(2)R became significantly suppressed in the B(1)R(-/-) mice in a
      manner quantitatively and directionally similar to that of wild-type mice. We
      conclude that both bradykinin receptors contribute to the cardioprotective
      bradykinin-mediated effect of ACE inhibition, not only the B(2)R as believed
      previously; but, whereas with potentiated bradykinin in the absence of B(1)R, the
      upregulation of B(2)R is simply insufficient to provide full cardioprotection, in
      the absence of B(2)R, the upregulated B(1)R actually seems to inflict further
      tissue damage.

PMID- 18347229
TI  - Screening, treatment, and control of hypertension in US private physician
      offices, 2003-2004.
AB  - Essential hypertension is the most common diagnosis in US primary care settings
      for middle-aged persons and seniors. Yet, data on hypertension screening,
      treatment, and control in such settings are limited. We analyzed National
      Ambulatory Medical Care Survey data to examine the rates of and factors
      associated with hypertension screening, treatment, and control during US office
      visits in 2003 and 2004. Blood pressure was measured in 56% (95% confidence
      limits: 52% to 59%) of all visits by patients > or =18 years of age and in 93%
      (95% confidence limits: 89% to 96%) of hypertensive patient visits. Among the
      latter, 62% (95% confidence limits: 55% to 69%) were treated. Diuretics were the
      most commonly prescribed antihypertensive agents (46%; 95% confidence limits: 41%
      to 50%), and combination therapy was reported in 58% (95% confidence limits: 54%
      to 63%) of treated visits. Only 39% (95% confidence limits: 34% to 43%) of
      treated visits were at recommended blood pressure goals. The odds of not being
      screened for hypertension were notably greater for visits with a provider other
      than a primary care physician or cardiologist (10.0; 95% confidence limits: 5.5
      to 16.7) and for nonwell care visits (5.6; 95% confidence limits: 3.6 to 8.3).
      Greater odds of not being treated for hypertension were noted by geographic
      region (South versus Northeast: 2.6; 95% confidence limits: 1.2 to 5.6) and visit
      type (first time versus return visits; 1.6; 95% confidence limits: 1.1 to 2.4).
      The odds of not having blood pressure controlled were greater for patients with
      comorbidities (1.6; 95% confidence limits: 1.1 to 2.4). In conclusion, more
      intervention efforts are needed to further reduce the gaps and variations in
      routine practice in relation to evidence-based practice guidelines for
      hypertension screening, treatment, and control.

PMID- 18347230
TI  - Modulation of reflex function by endogenous angiotensins in older transgenic rats
      with low glial angiotensinogen.
AB  - Age-related impairments in baroreflex sensitivity in Sprague-Dawley rats are
      associated with low solitary tract nucleus content of angiotensin-(1-7). However,
      transgenic rats with low-brain angiotensinogen resulting from glial
      overexpression of an antisense oligonucleotide to angiotensinogen (ASrAOGEN) are
      spared age-related declines in cardiovascular function characteristic of Sprague
      Dawley rats. We examine whether cardiovascular and reflex actions of angiotensin
      (1-7) persist in the solitary tract nucleus of older (16 to 22 months) ASrAOGEN
      rats. Baroreflex sensitivity for control of heart rate and chemosensitive vagal
      afferent activation in response to phenylbiguanide were measured before and after
      bilateral microinjection of the angiotensin II type 1 receptor antagonist
      candesartan and angiotensin-(1-7) receptor antagonist (D-Ala(7))-angiotensin-(1
      7) in urethane/chloralose-anesthetized rats. In older anesthetized ASrAOGEN rats,
      candesartan had no effect, whereas (D-Ala(7))-angiotensin-(1-7) significantly
      reduced baroreflex sensitivity (1.80+/-0.43 versus 0.50+/-0.17 ms/mm Hg).
      Phenylbiguanide responses were attenuated by injection of candesartan (-79+/-6
      versus -55+/-12 mm Hg and -277+/-12 versus -156+/-27 bpm; P<0.05). In addition,
      resting blood pressure was reduced by injection of candesartan or (D-Ala(7))
      angiotensin-(1-7). Within the solitary tract nucleus of older ASrAOGEN rats, it
      appears that glial angiotensinogen is the main source of angiotensin II
      attenuation of baroreflex sensitivity; endogenous angiotensin-(1-7) from nonglial
      sources enhances baroreflex sensitivity; nonglial sources of angiotensin II
      contribute to chemosensitive vagal afferent activation; and receptors for both
      peptides modulate resting arterial pressure under anesthesia. These results
      suggest a novel mechanism for the preservation of baroreflex sensitivity during
      aging.

PMID- 18347231
TI  - Glucocorticoid-related signaling effects in vascular smooth muscle cells.
AB  - Mineralocorticoid receptor blockade protects from angiotensin II-induced target
      organ damage. 11beta-Hydroxysteroid dehydrogenase type 2 protects the
      mineralocorticoid receptor from activation by glucocorticoids; however, high
      glucocorticoid concentrations and absent 11beta-hydroxysteroid dehydrogenase type
      2 in some tissues make glucocorticoids highly relevant mineralocorticoid receptor
      ligands. We investigated the effects of corticosterone (10(-6) to 10(-12) mol/L)
      on early vascular mineralocorticoid receptor signaling by Western blotting,
      confocal microscopy, and myography. Corticosterone initiated extracellular signal
      regulated kinase 1/2 phosphorylation in rat vascular smooth muscle cells at > or
      =10(-11) mol/L doses. Protein synthesis inhibitors had no effect, indicating a
      nongenomic action. Corticosterone also stimulated c-Jun N-terminal kinase, p38,
      Src, and Akt phosphorylation at 15 minutes and enhanced angiotensin II-induced
      signaling at 5 minutes. A specific epidermal growth factor receptor blocker,
      AG1478, as well as the Src inhibitor PP2, markedly reduced corticosterone-induced
      extracellular signal-regulated kinase 1/2 phosphorylation, as did preincubation
      of cells with the mineralocorticoid receptor antagonist spironolactone. Silencing
      mineralocorticoid receptor with small interfering RNA abolished corticosterone
      induced effects. Corticosterone (10(-9) mol/L) enhanced phenylephrine-induced
      contraction of intact aortic rings. These effects were dependent on the intact
      endothelium, mineralocorticoid receptor, and mitogen-activated protein kinase
      kinase 1/extracellular signal-regulated kinase signaling. We conclude that
      corticosterone induces rapid mineralocorticoid receptor signaling in vascular
      smooth muscle cells that involves mitogen-activated protein kinase
      kinase/extracellular signal-regulated kinase-dependent pathways. These new
      mineralocorticoid receptor-dependent signaling pathways suggest that
      glucocorticoids may contribute to vascular disease via mineralocorticoid receptor
      signaling, independent of circulating aldosterone.

PMID- 18347232
TI  - G protein-coupled receptor kinase 4: role in blood pressure regulation.

PMID- 18347233
TI  - Impact of cosmetic facial surgery on satisfaction with appearance and quality of
      life.
AB  - OBJECTIVES: To assess perioperative quality-of-life (QOL) changes in a facial
      plastic surgery patient population and to ascertain factors determinative of QOL
      changes. A notable paucity of objective scientific measurements of QOL exists
      within the facial plastic surgery literature. METHODS: A 3-year prospective
      cohort study. The patient population, which comprised a consecutive series of
      patients 16 years or older, undergoing cosmetic nasal or facial surgery, was
      obtained from the senior author's (P.A.A.) private surgical practice. All
      patients presenting for surgery were offered participation. The main outcome
      measure was the 59-item Derriford Appearance Scale (DAS59), a valid and reliable
      instrument assessing psychological distress associated with self-consciousness of
      facial appearance. Three patient score subgroupings were established: group 1,
      the DAS59 scores for all patients; group 2, the DAS59 score according to sex; and
      group 3, the DAS59 score according to the main surgical procedure. Surveys were
      administered to eligible patients at the final preoperative clinic visit and at 3
      months after surgery. Data from the case-control groups were analyzed by a
      blinded statistician with appropriate t tests. RESULTS: A total of 93 patients
      were enrolled with a 100% response rate (82 females [88%] and 11 males [12%]).
      The most common procedures were rhinoplasty (49%) and surgery for the aging face
      (51%). Marked differences in perioperative QOL were noted across all DAS59
      domains for group 1 and for all females in group 2. Male patients in group 2
      analysis experienced QOL improvement only from DAS59 domain 2 (General Self
      consciousness of Facial Appearance). Rhinoplasty and surgery for the aging face
      improved patients' QOL but differed with respect to which DAS59 domains were
      affected. CONCLUSIONS: Quality of life was enhanced by facial plastic surgery in
      this patient population. Male and female patients seem to have different needs to
      be met from facial cosmetic surgery and correspondingly different areas of
      improvement in QOL. Rhinoplasty and surgery for the aging face act on different
      domains of QOL.

PMID- 18347234
TI  - Botulinum toxin and quality of life in patients with facial paralysis.
AB  - OBJECTIVES: To examine the effect botulinum toxin, a potent neurotoxin that
      causes temporary paralysis of hyperkinetic musculature, has on the quality of
      life (QOL) in the patient with facial paralysis. We surveyed patients with facial
      paralysis, using the previously validated Facial Clinimetric Evaluation QOL
      instrument, before and then again after therapeutic administration of botulinum
      toxin for the management of their facial hyperkinesis, and performed pair-wise
      comparisons to determine the effect on patient QOL. DESIGN: Prospective clinical
      study at an outpatient facial nerve center. RESULTS: The overall Facial
      Clinimetric Evaluation score improved from a mean (SD) of 51.7 (20.9) in the
      pretreatment group to 63.7 (17.8) in the posttreatment group (P < .05).
      Statistically significant improvements were noted in all subdomain scores,
      including Facial Movement, Facial Comfort, Oral Function, Eye Comfort, Lacrimal
      Control, and Social Function (P < .05 for all comparisons). CONCLUSIONS:
      Botulinum toxin has a well-established objective benefit in the control of facial
      hyperkinesis in patients with facial nerve disorders. This study establishes the
      associated QOL benefit and reaffirms its important role in the multimodality
      management of patients with facial nerve disorders.

PMID- 18347235
TI  - Hockey-stick vertical dome division technique for overprojected and broad nasal
      tips.
AB  - OBJECTIVES: To discuss overprojected and broad nasal tips, to overview treatment
      options, and to relate our experience with the hockey-stick technique. DESIGN: A
      retrospective review (1975-2005) was conducted. Patients were selected from a
      computerized rhinoplasty database of operative cases. The database was used to
      extract a subset population that had received the hockey-stick tip procedure and
      had follow-up data for 1 year or more after surgery. Medical records and
      photographs were also analyzed in this review of results and complications.
      RESULTS: The hockey-stick modification of vertical dome division was used in 137
      patients (9.9% of the rhinoplasties in the computerized database). Of these, 64
      patients had 1 year or more of follow-up. Complications referable to the nasal
      tip (eg, bossae, persistent tip projection, and alar asymmetry) were seen in 8
      patients (13%). Revisions for tip-related problems were performed in 4 patients
      (6%). CONCLUSIONS: The hockey-stick technique is an effective method for nasal
      tip deprojection and narrowing via an endonasal approach. The length of follow-up
      in this patient population allows good long-term evaluation of this technique.

PMID- 18347236
TI  - Epidemiology and risk factors for pathologic scarring after burn wounds.
AB  - OBJECTIVE: To describe the clinical characteristics of postburn scars and
      determine the independent risk factors specific to these patients. While burns
      may generate widespread and disfiguring scars and have a dramatic influence on
      patient quality of life, the prevalence of postburn pathologic scarring is not
      well documented, and the impact of certain risk factors is poorly understood.
      METHODS: A retrospective analysis was conducted of the clinical records of 703
      patients (2440 anatomic burn sites) treated at the Turin Burn Outpatient Clinic
      between January 1994 and May 15, 2006. Prevalence and evolution time of postburn
      pathologic scarring were analyzed with univariate and multivariate risk factor
      analysis by sex, age, burn surface and full-thickness area, cause of the burn,
      wound healing time, type of burn treatment, number of surgical procedures, type
      of surgery, type of skin graft, and excision and graft timing. RESULTS:
      Pathologic scarring was diagnosed in 540 patients (77%): 310 had hypertrophic
      scars (44%); 34, contractures (5%); and 196, hypertrophic-contracted scars (28%).
      The hypertrophic induction was assessed at a median of 23 days after
      reepithelialization and lasted 15 months (median). A nomogram, based on the
      multivariate regression model, showed that female sex, young age, burn sites on
      the neck and/or upper limbs, multiple surgical procedures, and meshed skin grafts
      were independent risk factors for postburn pathologic scarring (Dxy 0.30).
      CONCLUSION: The identification of the principal risk factors for postburn
      pathologic scarring not only would be a valuable aid in early risk stratification
      but also might help in assessing outcomes adjusted for patient risk.

PMID- 18347237
TI  - Hematoma rates in drainless deep-plane face-lift surgery with and without the use
      of fibrin glue.
AB  - OBJECTIVE: To determine the rate of hematoma formation in drainless deep-plane
      rhytidectomy and compare it with the rate using the same technique with the use
      of fibrin glue. METHODS: This is a retrospective review of 605 patients (78 male
      and 527 female) who, over a 6-year period, underwent deep-plane face-lift surgery
      (n = 544) or lateral superficial musculoaponeurotic system (SMAS)ectomy (n = 61)
      by the senior author (S.S.R.) without the use of surgical drains. One hundred
      forty-six consecutive patients underwent rhytidectomy without fibrin tissue glue,
      and the following 459 consecutive patients were sprayed with fibrin glue under
      the flap prior to flap closure. Pressure dressings were used on all patients for
      24 hours. RESULTS: None of the patients in either group had major or expanding
      hematomas requiring operative intervention. In the group of patients treated
      without fibrin glue (n = 146), there were 5 minor, nonexpanding hematomas, all
      managed by needle aspiration. This is a minor hematoma rate of 3.4%. In the
      fibrin glue group (n = 459), there were 2 hematomas, for a rate of 0.4%. Using a
      Fisher exact test, we found a statistically significant decrease in the hematoma
      rate from 3.4% to 0.4% (P = .01). Male patients had a higher hematoma rate than
      female patients, and only men had significantly fewer hematomas when fibrin glue
      was applied (P = .01). All 7 hematomas were recognized in the first 24 hours
      after surgery. Of the 7 patients with hematomas, 2 (29%) had emesis in the
      recovery room despite medication. CONCLUSIONS: The use of fibrin glue
      demonstrates a significant decrease in the rate of hematoma formation. Fibrin
      glue may benefit male more than female patients. If meticulous hemostasis and
      pressure dressings are used, drains are not necessary. The prevention and prompt
      treatment of postoperative nausea may also help prevent hematoma formation.

PMID- 18347238
TI  - An anatomical study of the nasal superficial musculoaponeurotic system: surgical
      applications in rhinoplasty.
AB  - OBJECTIVE: To give a unifying description of nasal muscles and ligaments
      corresponding to anatomical and surgical findings such as the dermocartilaginous
      ligament described by Pintanguy in 2001. METHODS: In 30 fresh cadavers of white
      individuals, nasal dissections were performed, divided into 3 different
      approaches: from radix to nasal tip, from nasal tip to radix, and from midline to
      lateral. The anatomical and surgical planes of dissection were followed to
      isolate the nasal superficial musculoaponeurotic system (SMAS). Correlations
      between the nasal SMAS and the nasal framework were noticed. In 9 specimens, the
      left nasal wall was resected for histologic examination. RESULTS: The nasal SMAS
      consists of a unique layer, and it divides at the level of the nasal valve into
      deep and superficial layers. Each layer has medial and lateral components. The
      dermocartilaginous ligament corresponds to the deep medial expansion. Both the
      deep and the superficial medial expansions correspond to the lowering ligaments
      of the nasal tip; the cephalic rotation of the nasal tip is allowed by their cut.
      The histological examination showed that the deep lateral expansion is composed
      of fat. CONCLUSIONS: This description of the nasal SMAS explains the relationship
      between the nasal muscles and ligaments, including the dermocartilaginous
      ligament described by Pitanguy. Furthermore, it is helpful to surgeons during
      rhinoplasty.

PMID- 18347239
TI  - Methicillin-resistant Staphylococcus aureus--positive surgical site infections in
      face-lift surgery.
AB  - OBJECTIVES: To determine the incidence of methicillin-resistant Staphylococcus
      aureus (MRSA)-positive surgical site infections after face-lift surgery and to
      discuss the screening, prevention, and treatment of such infections. METHODS: The
      patient charts of 780 patients who underwent a deep-plane rhytidectomy between
      2001 and 2007 were reviewed for postoperative wound infections. Culture results
      and sensitivities were recorded. To our knowledge, this is the first study that
      documents MRSA-positive surgical site infections after face-lift surgery.
      RESULTS: Five of 780 patients (0.6%) who underwent face-lift surgery by the
      senior surgeon had postoperative surgical site infections. Four of the 5 patients
      had cultures that were positive for MRSA. Two of these patients (0.3%) required
      hospitalization and had collections that had to be opened or drained and
      developed wound breakdown. Both patients eventually responded to wound care along
      with intravenous and then oral antibiotic therapy. The other 2 MRSA-infected
      patients responded to oral antibiotic therapy and local wound care alone. The 2
      complicated infections occurred on postoperative days 5 and 8. These 2 patients
      were the only ones among the 5 patients with positive cultures who had known
      recent contact with another physician or a hospital. All infections occurred in
      the year 2006, with 3 patients experiencing infection in the last 4 months of the
      year. Herein, we describe the incidence and sequelae of MRSA infections and
      colonization. The 2 major different subsets of MRSA are community-acquired MRSA
      and health care-associated MRSA. Surgical site infections that are positive for
      MRSA blur this division, which affects many aspects of the course of disease and
      treatment. We also discuss strategies for screening, preventing, and treating
      MRSA surgical site infections. CONCLUSIONS: Methicillin-resistant S aureus
      positive surgical site infection is an increasingly problematic issue in all
      surgical fields. In the future, MRSA-positive infections will be more prevalent
      and will require well-developed screening, prevention, and treatment strategies.

PMID- 18347240
TI  - Effects of different suture materials on cartilage reshaping.
AB  - OBJECTIVE: To examine the effects of different suture materials and suturation
      techniques on cartilage reshaping in a rabbit model. METHODS: Twenty-two rabbits
      were used. Posterior skin flaps were elevated, and 4 cartilage struts were
      prepared on each auricula. Each strut was bent at its midpoint, and the skin
      under the bent area was elevated only in 1 side. The strut was sutured either
      with catgut, polyglactin 910, polydioxanone, or polypropylene sutures.
      Anteriorly, the suture was passed subcutaneously on 1 side, while
      transcutaneously on the other. Animals were killed at the first and fourth
      months. The shape of the struts was macroscopically evaluated. Inflammation and
      foreign body reaction around the suture were examined under light microscopy.
      RESULTS: Maintenance of shape with all suture materials was significantly lower
      in the transcutaneously sutured group than in the subcutaneously sutured group.
      Because of high rates of suture loss in the transcutaneously sutured group,
      further evaluations on cartilage tissue were made only in subcutaneously sutured
      group. Success rate in maintenance of shape was similarly high in the
      polydioxanone, polyglactin 910, and polypropylene suture groups; however, it was
      significantly lower in the catgut suture group. CONCLUSION: Long-lasting
      absorbable suture materials are as effective as nonabsorbable ones, and the
      subcutaneous technique is more effective than the transcutaneous technique.

PMID- 18347241
TI  - Reconstruction of nasal sidewall defects after excision of nonmelanoma skin
      cancer: analysis of uncovered subcutaneous hinge flaps allowed to heal by
      secondary intention.
AB  - OBJECTIVE: To describe the experience of a single department using uncovered
      subcutaneous hinge flaps to repair the nasal portion and adjacent facial subunits
      of defects after skin tumor excision. DESIGN: Case series of 16 patients needing
      reconstruction for lesions of the alar subunit with 1 or more adjacent facial
      subunits after Mohs surgery for cutaneous malignant neoplasms. RESULTS: All flaps
      healed well by secondary intention, and the results were gauged at least
      satisfactory by the patients and surgeons. In 4 patients there were minor
      aesthetic concerns: in 1 patient the underlying cartilage graft was prominent and
      a minor revision was undertaken, 1 patient had effacement of the nasofacial
      sulcus, 1 patient developed a hypertrophic scar, and 1 patient developed both
      effacement of the nasofacial sulcus and a scar. CONCLUSIONS: The use of
      subcutaneous hinge flaps allowed to heal by secondary intention is a simple 1
      stage technique that may be useful in reconstruction of small but deep nasal
      sidewall defects.

PMID- 18347243
TI  - Volumetric imaging of the malar fat pad and implications for facial plastic
      surgery.

PMID- 18347244
TI  - A follow-up study of the Monarch adjustable implant for correction of nasal valve
      dysfunction.

PMID- 18347246
TI  - Medical professionalism.

PMID- 18347247
TI  - Changes in quality of life over 1 year in patients with head and neck cancer.
AB  - OBJECTIVES: To characterize and compare quality of life (QOL) in patients with
      head and neck cancer shortly before initial treatment and 1 year later and to
      study the predictors of changes in QOL over 1 year. DESIGN: Prospective cohort
      study. SETTING: Three otolaryngology clinics. PATIENTS: Three hundred sixteen
      patients having newly diagnosed squamous cell head and neck cancer. MAIN OUTCOME
      MEASURE: Health-related QOL was assessed using the 36-item Short-Form Health
      Survey and a head and neck cancer-specific QOL scale. RESULTS: Over 1 year, QOL
      decreased for physical functioning measures and eating but improved for mental
      health QOL. Depression and smoking were major predictors of poor QOL at baseline.
      Major predictors of change in QOL from baseline to 1 year were treatment factors,
      especially feeding tube placement (9 scales), chemotherapy (3 scales), and
      radiation therapy (3 scales). Baseline smoking and depressive symptoms also
      remained significant predictors of several QOL scales at 1 year. CONCLUSIONS:
      Health-related physical QOL tended to decline over 1 year and mental health QOL
      improved. The major predictors of change in QOL were treatment factors, smoking,
      and depressive symptoms. Physicians should alert patients to the relative effects
      on QOL one may experience with different treatments.

PMID- 18347248
TI  - The role of pyrosequencing in head and neck cancer epigenetics: correlation of
      quantitative methylation data with gene expression.
AB  - OBJECTIVE: To evaluate promoter methylation quantitation using recently described
      pyrosequencing techniques by correlation with messenger RNA (mRNA) expression.
      DESIGN: DNA was extracted from tissue samples and was subjected to bisulphite
      conversion. Quantitative methylation data for multiple CpG sites in each of 9
      gene promoters were obtained for tumors using pyrosequencing. RNA was extracted
      and converted to complementary DNA, and this formed the template for relative
      quantitation assays of the expression of each gene by real-time reverse
      transcription-polymerase chain reaction. SETTING: Academic research. PATIENTS:
      Thirty-seven patients with head and neck squamous cell carcinoma. MAIN OUTCOME
      MEASURES: The genes studied were P16 (OMIM 600160), cyclin A1 (OMIM 604036), RARB
      (OMIM 180220), E-cadherin (OMIM 192090), MGMT (OMIM 156569), STAT1 (OMIM 600555),
      ATM (OMIM 607585), hMLH1 (OMIM 120436), and TIMP3 (OMIM 188826).
      Immunohistochemistry was also performed for p16. RESULTS: STAT1, TIMP3, ATM, and
      hMLH1 promoters were essentially unmethylated in all cases. The data for cyclin
      A1 (Spearman rank correlation, rho = -0.53; P < .001), MGMT (rho = -0.53, P <
      .001), and RARB (rho = -0.34, P =.02) showed the expected negative correlation
      between levels of methylation and mRNA expression. The data relating to E
      cadherin were inconclusive. Surprisingly, P16 expression was statistically
      significantly greater in those cases with higher levels of methylation (rho =
      0.57, P < .001), a finding at odds with assumptions usually made in the
      literature relating gene promoter methylation to reduced gene expression. The
      results from p16 immunohistochemistry were in keeping with the mRNA data, but the
      number of positive staining samples proved too few for statistical analysis.
      CONCLUSIONS: These data present a novel perspective on head and neck cancer
      epigenetics and reveal new and some unexpected associations and findings. The
      advantages of pyrosequencing over nonquantitative techniques are discussed in
      analyses of this nature.

PMID- 18347249
TI  - Absence of planned neck dissection for the N2-N3 neck after chemoradiation for
      locally advanced squamous cell carcinoma of the head and neck.
AB  - OBJECTIVE: To review our institutional experience of patients with locally
      advanced squamous cell carcinoma of the head and neck (SCCHN) and N2-N3 neck
      disease with respect to neck recurrence after chemoradiation without planned neck
      dissection (ND). DESIGN: Retrospective study. SETTING: Tom Baker Cancer Centre,
      Calgary, Alberta, Canada. PATIENTS: Fifty-four adults with locally advanced SCCHN
      and N2-N3 neck disease. INTERVENTIONS: Eighty consecutive patients were treated
      with chemoradiation, 70 Gy given as 2 Gy daily for 7 weeks, with cisplatin, 20
      mg/m(2), given on the first 4 days of weeks 1 and 5. Of the 80 patients, 54 were
      evaluable. MAIN OUTCOME MEASURES: Primary outcomes were overall survival and
      absence or presence of neck disease after chemoradiation. Secondary outcomes
      included disease-specific survival and locoregional recurrence-free survival.
      RESULTS: Median follow-up of living patients was 35 months. Patients with a
      complete response (CR) did not have any planned ND. Factors associated with the
      absence of recurrent neck disease included CR (P < .001), younger age (P = .02),
      and better Karnofsky Performance Status (P = .049). In patients achieving CR, 2
      year overall, disease-specific, and locoregional recurrence-free survival was
      92%, 95%, and 95%, respectively. Three of the 43 patients (7%) with N2 lesions
      obtaining CR subsequently experienced a neck recurrence at a median of 15 months
      (range, 7-24 months). CONCLUSIONS: In these patients with locally advanced SCCHN
      and N2-N3 neck disease treated with chemoradiation and achieving CR, only a few
      patients with N2 neck disease experienced recurrence despite the absence of
      planned ND. Prospective trials are needed to identify patients with N2 neck
      disease who may still benefit from planned ND after chemoradiation. There were
      not enough patients with N3 neck disease to make any recommendations.

PMID- 18347250
TI  - Infant tracheotomy: results of a survey regarding technique.
AB  - OBJECTIVE: To identify practice patterns regarding tracheotomy technique among
      pediatric otolaryngologists. DESIGN: Survey of physicians. SETTING: Academic
      medical center. PARTICIPANTS: Members of the American Society of Pediatric
      Otolaryngology (ASPO) residing in the United States. MAIN OUTCOME MEASURES:
      Physician responses to survey questions, including both multiple choice and free
      text responses. We used chi(2) tests to determine if demographic factors
      (pediatric otolaryngology fellowship training, the number of tracheotomies
      performed yearly) correlated with differences in the technique used to perform
      infant tracheotomies. RESULTS: A total of 168 of 225 surveys mailed to ASPO
      members (75%) were completed and returned. Most respondents (87%) report that
      they make a simple vertical incision in the trachea. An even greater number (94%)
      use stay sutures routinely. On other technical points, such as management of the
      thyroid gland, the subcutaneous fat, and the method of securing the tracheostomy
      tube, there was much greater variability: 22% of respondents reported having had
      a serious tracheotomy-related complication in the immediate postoperative period,
      and 58% of these physicians changed their technique as a result. In several
      areas, chi(2) analysis revealed statistically significant differences in
      technique that were dependent on both fellowship training and the number of
      tracheotomies performed (P < or = .05). CONCLUSIONS: Among ASPO members
      practicing in the United States, there is near-unanimity on certain technical
      points, with considerable divergence on others. A substantial percentage of our
      colleagues have experienced a tracheotomy-related complication in the early
      postoperative period. In many cases, these incidents led to changes in surgical
      technique.

PMID- 18347251
TI  - Injection pharyngoplasty with calcium hydroxyapatite for treatment of velopalatal
      insufficiency.
AB  - OBJECTIVE: To evaluate the efficacy of injectable calcium hydroxylapatite for
      treatment of velopalatal (VP) insufficiency (VPI). DESIGN: Observational case
      series of 7 patients treated with injectable calcium hydroxylapatite for VPI and
      followed for 10 to 24 months. SETTING: Academic pediatric otolaryngology
      practice. PATIENTS: Seven children aged 6 to 16 years with clinically significant
      VPI stemming from documented small VP gaps and who did not benefit from speech
      therapy were treated with calcium hydroxylapatite injection pharyngoplasty.
      INTERVENTION: Posterior pharyngeal wall augmentation with calcium
      hydroxylapatite. MAIN OUTCOME MEASURES: Treatment success was defined as (1)
      speech improvement to the degree that parents felt no additional treatment was
      needed and (2) meeting postoperative nasometric measures. Treatment failure was
      defined as parental report of insufficient improvement in speech. Complications
      and additional treatments for VPI were noted. RESULTS: There were no major
      complications in any of the 7 children injected with calcium hydroxylapatite.
      There was 1 minor complication: 1 patient was readmitted for postoperative pain
      and dehydration. Of the 7 patients, 4 experienced a satisfactory result for up to
      17 months. Findings from postoperative nasometry were either within reference
      range, or less than 1 SD greater than the reference range, for all sounds. There
      were 3 treatment failures, each with preexisting craniofacial abnormality. Two
      patients in the group that failed treatment later underwent revision superior
      pharyngeal flap surgery without complication or hindrance from the calcium
      hydroxylapatite injection. Four children underwent subsequent magnetic resonance
      imaging evaluations up to 1 year after injection, which revealed no evidence of
      migration. CONCLUSIONS: The data from this small series suggest that posterior
      pharyngeal wall injection with calcium hydroxylapatite is safe and may be
      effective in treating select patients with VPI. Further longitudinal studies,
      with a larger series of patients, examining the safety, efficacy, and patient
      selection are warranted to better understand the possible use of posterior
      pharyngeal wall injection of calcium hydroxylapatite in children with symptomatic
      VPI.

PMID- 18347252
TI  - Lobular capillary hemangioma of the neonatal larynx.
AB  - OBJECTIVE: To describe a previously unreported condition of the neonatal larynx.
      DESIGN: Case series of 4 neonates with an uncommon laryngeal lesion. SETTING:
      Tertiary care children's hospital. PATIENTS: Four neonates in the first 10 days
      of life with stridor, hoarseness, and respiratory distress. INTERVENTION: The
      patients were examined using flexible fiberoptic laryngoscopy, and laryngeal
      lesions were identified and subsequently removed using microlaryngoscopy.
      Photodocumentation of the lesions was performed. Microscopic evaluation of biopsy
      specimens by a pathologist followed. MAIN OUTCOME MEASURES: Each patient's
      medical record was carefully reviewed for prenatal history, birth history,
      neonatal history, pathologic findings, and office follow-up. RESULTS: All 4
      neonates were delivered atraumatically and developed symptoms of upper airway
      obstruction within the first few minutes to days of life. Each neonate was found
      to have an obstructive laryngeal lesion requiring surgical intervention. No child
      had other congenital abnormalities or a history of obvious laryngeal trauma.
      Pathologic review of each laryngeal specimen revealed inflammatory lesions with
      characteristic features of a lobular capillary hemangioma (or a pyogenic
      granuloma). CONCLUSIONS: The diagnosis of a lobular capillary hemangioma of the
      larynx should be considered in the differential diagnosis of a newborn with
      stridor, hoarseness, or respiratory distress. The cases seem to be of congenital
      origin, although acquired pathogenesis cannot be ruled out. Treatment of these
      lesions includes microscopic surgical excision.

PMID- 18347253
TI  - Breathing and voice quality after surgical treatment for bilateral vocal cord
      paralysis.
AB  - OBJECTIVE: To evaluate long-term results of surgical treatment for bilateral
      vocal cord paralysis using objective and subjective measures of breathing and
      voice quality. DESIGN: Prospective cross-sectional case series. SETTING: Tertiary
      care otolaryngology and speech pathology referral center. PATIENTS: Ten patients
      with bilateral vocal cord paralysis who underwent surgical treatment between
      October 1996 and May 2006 at the Department of Otorhinolaryngology-Head and Neck
      Surgery, University of Wurzburg, were examined at a mean of 27.2 months after
      surgery. MAIN OUTCOME MEASURES: Glottal area, voice range profile, Voice Handicap
      Index, pulmonary function test results, Gottingen Hoarseness Diagram,
      microlaryngostroboscopic findings, chronic respiratory disease questionnaire, and
      European Organization for Research and the Treatment of Cancer quality-of-life
      questionnaire, including the head and neck module. RESULTS: Residual recurrent
      nerve function was seen in 9 of 10 patients. Pulmonary data varied widely and did
      not correlate with the size of the glottal area. Quality of life, subjective
      dyspnea, and physical functioning correlated with expiratory airflow measures.
      Voice range was reduced in all patients. High breathiness and reduced maximum
      phonation time led to increased Voice Handicap Index scores. CONCLUSIONS:
      Microlaryngostroboscopic findings did not necessarily correlate with subjective
      dyspnea and vocal complaints. Reduction of inspiratory speaking efforts and
      acquisition of special breathing techniques improve airflow stability and
      effectiveness of respiration, leading to enhanced quality of life.

PMID- 18347254
TI  - Lateral lamella of the cribriform plate: software-enabled computed tomographic
      analysis and its clinical relevance in skull base surgery.
AB  - OBJECTIVE: To describe a quantitative analysis of the lateral lamella of the
      cribriform plate (LLCP) height in computed tomographic (CT) images. The LLCP is
      the thinnest anatomic structure in the skull base. DESIGN: Software-enabled CT
      scan measurements. SETTING: Academic center. RESULTS: The CT scans from 50
      patients were analyzed. The median height of the LLCP in 100 sides was 2.4 mm.
      The LLCP height was 0 to 3.9 mm in 83 sides, 4.0 to 7.0 mm in 15 sides, and
      greater than 7.0 mm in 2 sides. When analyzing differences among sides, the LLCP
      height was greater on the right side in 28 patients and greater on the left side
      in 22. The differences between sides was 0 to 1.9 mm in 39 patients, 2.0 to 3.9
      mm in 9 patients, and greater than 4.0 mm in 2 patients. CONCLUSIONS: Computer
      aided CT scan analysis allows for a quantitative analysis of the paranasal sinus
      skull base anatomy. Knowledge of these dimensions is invaluable during surgical
      planning and navigation. Asymmetry of the relative ethmoid roof position is
      common. Thus, the rhinologic surgeon must exercise caution to prevent
      unintentional skull base injury and cerebrospinal fluid leak.

PMID- 18347255
TI  - The contralateral ear in chronic otitis media: a series of 500 patients.
AB  - OBJECTIVE: To study the contralateral ear of patients with chronic otitis media
      (COM). DESIGN: Transversal. SETTING: Tertiary referral center. PATIENTS: A total
      of 500 consecutive patients who had been diagnosed as having COM with or without
      cholesteatoma. INTERVENTIONS: Digital otoendoscopy was performed on both ears.
      MAIN OUTCOME MEASURE: Pathologic alterations in the contralateral ear. RESULTS:
      In 75.2% of the patients, the contralateral ear was found to have some structural
      abnormalities; 60.4% of the patients presented with COM without cholesteatoma,
      and in this group, 69.9% had an abnormal contralateral ear. In those with
      cholesteatoma, the contralateral ear was found to be abnormal in 83.3%. The most
      frequent finding in both groups was retraction of the tympanic membrane.
      CONCLUSIONS: Patients with COM in 1 ear have a high chance of presenting with
      some degree of disease in the contralateral side. We believe that our findings
      suggest that COM should be ideally approached not as a static pathological
      incident affecting 1 ear but rather as an on-going process that may affect both
      ears.

PMID- 18347256
TI  - Audiometric characteristics of a Dutch family linked to DFNA15 with a novel
      mutation (p.L289F) in POU4F3.
AB  - OBJECTIVE: To report on the audiometric characteristics of a large Dutch family
      linked to DFNA15 with a novel mutation (p.L289F) in POU4F3 (OMIM 602460). DESIGN:
      Clinical investigation. SETTING: Tertiary referral center. PATIENTS: Family
      members from a large 5-generation pedigree with sensorineural hearing impairment
      segregating as an autosomal dominant trait. MAIN OUTCOME MEASURES: Cross
      sectional and longitudinal analyses of pure-tone audiometric data, and cross
      sectional analyses of speech audiometry data. RESULTS: Overall, a flat to gently
      downsloping audiometric configuration was observed with a progression rate of
      approximately 0.8 dB/y across most frequencies. Speech recognition scores
      remained fairly good in relation to age and hearing level compared with a group
      of patients with presbycusis. Interindividual variability was observed in terms
      of subjective onset age and audiometric configuration. Two mutation carriers, who
      reported vestibular symptoms, underwent vestibular examination and showed
      hypofunction of the vestibular labyrinth. CONCLUSIONS: The audiometric phenotype
      of the Dutch family linked to DFNA15 with a novel mutation in POU4F3 is
      comparable to that observed in the original Israeli family linked to DFNA15.
      Relatively good speech recognition scores suggest outer hair cell involvement.
      DFNA15 may represent a cochleovestibular disorder.

PMID- 18347257
TI  - Expression of chloride channel protein CLC-3 in patients with allergic rhinitis:
      effect of topical corticosteroid treatment.
AB  - OBJECTIVES: To determine whether the chloride channel protein CLC-3 is
      upregulated in patients with allergic rhinitis (AR) and whether topical
      corticosteroid treatment decreases the expression of CLC-3. DESIGN: Histologic
      study. SETTING: Academic research. PATIENTS: Eighteen patients with AR were
      included in the study. MAIN OUTCOME MEASURES: Expression of CLC-3 was detected by
      immunohistochemistry and by reverse transcription-polymerase chain reaction
      before and at 4 weeks after treatment with the topical corticosteroid mometasone
      furoate. RESULTS: Strong CLC-3 expression was detected in epithelium and in
      submucosal glands. An increased presence of CLC-3 was demonstrated in nasal
      mucosa compared with that in normal nasal tissue. A statistically significant
      difference in CLC-3 gene expression level was found in nasal tissues before vs at
      4 weeks after treatment with mometasone. CONCLUSIONS: CLC-3 may have a role in
      modulating the pathogenesis of AR. Decreased expression of CLC-3 may be the
      mechanism of action of corticosteroid treatment in controlling AR.

PMID- 18347258
TI  - Identification of Id1 in acquired middle ear cholesteatoma.
AB  - OBJECTIVES: To determine (1) the relationship between chronic inflammatory
      changes in the ossicular chain area (OCA) and the formation of cholesteatoma and
      (2) the correlates between aberrant gene expression and abnormal proliferation of
      cholesteatoma. METHODS: Two hundred sixty-four ears with chronic otitis media
      that had undergone ear surgery were included in this study for statistical
      analysis of the relationship between abnormalities in the OCA and cholesteatoma.
      Fourteen middle ear cholesteatoma specimens were collected for
      immunohistochemical analysis of candidate molecules involved in the abnormal
      proliferation of keratinocytes. A cell model was used for verification of
      candidate molecule involvement. RESULTS: The formation of cholesteatoma was
      accompanied by chronic inflammatory changes in the OCA, including granulated
      tissue, adhesion, and stagnating effusion. The inhibitor of the DNA-binding (Id1)
      gene, which is involved in controlling cell cycle progression, was abundantly
      expressed in cholesteatoma epithelium. In vitro studies indicate that Id1
      regulated the expression of nuclear factor kappaB, cyclin D1, proliferating cell
      nuclear antigen, and cell cycle progression of keratinocytes, CONCLUSIONS:
      Chronic inflammation in the OCA is closely related to the formation of
      cholesteatoma. The Id1/nuclear factor kappaB/cyclin D1/proliferating cell nuclear
      antigen signaling pathway is involved in the abnormal proliferation of
      keratinocytes in acquired cholesteatoma.

PMID- 18347259
TI  - Classification of the deviated nose and its treatment.
AB  - OBJECTIVE: To present a simplified classification of the deviated nose and the
      associated treatment outcome. DESIGN: Retrospective analysis. SETTING: Tertiary
      care rhinology clinic. PATIENTS: Seventy-five individuals (49 males and 26
      females) who underwent rhinoplasty for a deviated nose with minimum follow-up of
      36 months. MAIN OUTCOME MEASURES: Depending on the orientation of 2 horizontal
      subunits (the bony pyramid and the cartilaginous vault) with respect to the
      facial midline, the nasal deviations are classified into 5 types: I, a straight
      tilted bony pyramid with a straight tilted cartilaginous vault in the opposite
      direction; II, a straight tilted bony pyramid with a concavely or convexly bent
      cartilaginous vault; III, a straight bony pyramid with a tilted cartilaginous
      vault; IV, a straight bony pyramid with a bent cartilaginous vault, and V, a
      straight tilted bony pyramid and a tilted cartilaginous dorsum in the same
      direction. RESULTS: Deformities of types I through V occurred in 24 (32%), 19
      (25%), 19 (25%), 7 (9%), and 6 (8%) patients, respectively, in whom 1, 3, 2, 1,
      and 1 unsuccessful outcomes were found. Four of the 8 failed cases had been
      approached endonasally. CONCLUSION: The proposed classification for the deviated
      nose could serve as a valuable adjunct in the treatment of these patients.

PMID- 18347260
TI  - Expression and distributional patterns of the inhibitor of apoptosis protein
      family and caspase 3 in nasal polyps.
AB  - OBJECTIVES: To investigate the expression and distributional patterns of the
      inhibitor of apoptosis protein (IAP) family and caspase 3 in nasal polyps and
      normal nasal mucosa and to evaluate the possible effects of the IAP family and
      caspase 3 on the development of nasal polyps. DESIGN: Prospective study. SETTING:
      Tertiary academic institution. PATIENTS: Normal inferior turbinate mucosa was
      obtained from 20 patients undergoing surgery for augmentation rhinoplasty. Nasal
      polyps were obtained from 20 patients undergoing endoscopic sinus surgery for
      chronic polypoid sinusitis. INTERVENTIONS: Reverse transcriptase-polymerase chain
      reaction, immunohistochemical analysis, and Western blot analysis were performed.
      MAIN OUTCOME MEASURES: The expression and distribution of cIAP1, cIAP2, XIAP,
      survivin, and caspase 3 were evaluated in normal turbinate mucosa and nasal
      polyps. RESULTS: cIAP1, cIAP2, and XIAP were expressed in normal human nasal
      mucosa, where they were detected in submucosal glands, epithelial cells, vascular
      endothelial cells, and inflammatory cells. However, cIAP1 was not expressed in
      nasal polyps, whereas cIAP2 and XIAP were expressed in submucosal glands,
      epithelial cells, vascular endothelial cells, and inflammatory cells. Caspase 3
      was localized to a portion of the epithelial cells in normal nasal mucosa and
      nasal polyps. Survivin was not expressed in any samples. Furthermore, cIAP2,
      XIAP, and caspase 3 did not show a significant difference in their expression
      levels between normal nasal mucosa and nasal polyps. CONCLUSION: The present
      results indicate that cIAP1, cIAP2, XIAP, and caspase 3 may regulate the
      homeostasis of normal nasal mucosa, whereas cIAP2, XIAP, and caspase 3 may take
      part in the pathogenesis of nasal polyps.

PMID- 18347261
TI  - Alternative to tracheotomy in a newborn with CHARGE association.

PMID- 18347262
TI  - Chronic pachymeningitis and bilateral facial paralysis secondary to renal
      osteodystrophy.

PMID- 18347263
TI  - Radiology quiz case 1. Ameloblastoma.

PMID- 18347264
TI  - Radiology quiz case 2. Pigmented villonodular synovitis of the temporomandibular
      joint.

PMID- 18347265
TI  - Pathology quiz case 1. Sclerosing mucoepidermoid carcinoma with eosinophilia
      (SMECE).

PMID- 18347266
TI  - Pathology case quiz 2. Solitary fibrous tumor of the nasal cavity and ethmoid
      sinus with intracranial extension.

PMID- 18347267
TI  - Effect of generational composition on the surgical workforce.

PMID- 18347268
TI  - Use of gene expression profiles in cells of peripheral blood to identify new
      molecular markers of acute pancreatitis.
AB  - HYPOTHESIS: Blood leukocytes play a major role in mediating local and systemic
      inflammation during acute pancreatitis. We hypothesize that peripheral blood
      mononuclear cells (PBMCs) in circulation exhibit unique changes in gene
      expression and could provide a "reporter" function that reflects the inflammatory
      response in the pancreas with acute pancreatitis. DESIGN: To determine specific
      changes in blood leukocytes during acute pancreatitis, we studied the gene
      transcription profile in PBMCs in a rat model of experimental pancreatitis
      (sodium taurocholate). Normal rats, saline controls, and a model of septic shock
      were used as a controls. Complementary RNA obtained from PBMCs of each group (n =
      3 in each group) were applied to Affymetrix rat genome DNA GeneChip arrays. Main
      Outcome Measure Changes in gene expression. RESULTS: From the 8799 rat genes
      analyzed, 140 genes showed unique significant changes in their expression in
      PBMCs during the acute phase of pancreatitis, but not in sepsis. Among the 140
      genes, 57 were up-regulated, while 69 were down-regulated. Platelet-derived
      growth factor receptor, prostaglandin E(2) receptor, and phospholipase D(1) were
      among the top up-regulated genes. Others included genes involved in G protein
      coupled receptor and transforming growth factor beta-mediated signaling pathways,
      while genes associated with apoptosis, glucocorticoid receptors, and even the
      cholecystokinin receptor were down-regulated. CONCLUSIONS: Microarray analysis in
      transcriptional profiling of PBMCs showed that genes that are uniquely related to
      molecular and pancreatic function display differential expression in acute
      pancreatitis. Profiling genes obtained from an easily accessible source during
      severe pancreatitis may identify surrogate markers for disease severity.

PMID- 18347269
TI  - Association of morbid obesity with FTO and INSIG2 allelic variants.
AB  - OBJECTIVE: To determine whether 2 single nucleotide polymorphisms (SNPs) in the
      obesity genes the fat mass and obesity associated gene (FTO) and the insulin
      induced gene 2 (INSIG2) are associated with class III, or morbid, obesity in
      patients undergoing bariatric weight loss operations. DESIGN: Retrospective
      analysis of genotype and clinical data. SETTING: Large rural tertiary care health
      system. PATIENTS: A total of 707 adult patients with a body mass index (BMI;
      calculated as weight in kilograms divided by height in meters squared) of at
      least 40 undergoing open or laparoscopic Roux-en-Y gastric bypass operations for
      morbid obesity or its comorbid medical problems at Geisinger Medical Center,
      Danville, Pennsylvania. RESULTS: The mean BMI in the predominantly white female
      cohort was 51.2. Approximately 21% of patients were homozygous for the FTO
      obesity SNP variant, 13% were homozygous for the INSIG2 obesity SNP variant, and
      3.4% were homozygous for both. Mean BMIs in the groups homozygous for each of
      these genes were not significantly different from nonhomozygotes. However,
      FTO/INSIG2 double homozygotes and homozygote/heterozygote pairs had significantly
      higher BMIs than the other groups. CONCLUSION: Increased BMI in morbid obesity is
      associated with a combination of FTO and INSIG2 SNPs.

PMID- 18347270
TI  - B-type natriuretic peptide: a biomarker for the diagnosis and risk stratification
      of patients with septic shock.
AB  - BACKGROUND: The importance of cardiomyocyte damage during sepsis has been a
      recent subject of interest. The progression of sepsis results in the upregulation
      of proinflammatory cytokines, which act in concert to damage cardiomyocytes and
      produce cardiac contractile dysfunction. B-type natriuretic peptide (BNP) is a
      neurohormone released from the ventricles of the heart in response to myocardial
      dysfunction. The goal of this study was to examine the relationship between BNP
      levels and the severity of sepsis independent of congestive heart failure.
      DESIGN: Prospective, nonrandomized control study. SETTING: University hospital.
      PATIENTS: Forty-nine patients were divided into 3 groups: 13 patients with septic
      shock, 18 with early sepsis, and 18 age-matched healthy control subjects. We
      excluded patients with septic shock who had comorbid conditions (congestive heart
      failure or renal failure); sepsis severity was determined using the Sequential
      Organ Failure Assessment scoring system. Patients with sepsis were followed up
      for 21 days. MAIN OUTCOME MEASURES: Serum BNP levels, determined at the time of
      diagnosis of sepsis and on patient improvement or deterioration. RESULTS:
      Patients with septic shock had significantly higher BNP levels on admission
      compared with the other 2 groups (P < .05). The BNP levels were not significantly
      elevated in patients with early sepsis. Plasma BNP levels for patients with
      septic shock were positively correlated with Sequential Organ Failure Assessment
      scores (r(2) = 0.74, P < .05) and prognosticated survival. CONCLUSIONS: This
      study confirms the relationship between BNP level elevation and severity of
      sepsis independent of congestive heart failure. It also supports the utility of
      BNP level as a marker for mortality in septic shock.

PMID- 18347271
TI  - Prognostic utility of postoperative C-reactive protein for posthepatectomy liver
      failure.
AB  - HYPOTHESIS: C-reactive protein (CRP) is an acute-phase protein produced by the
      liver. We hypothesize that an early dampened CRP response after major liver
      resection is of prognostic importance in predicting posthepatectomy liver failure
      (PHLF). DESIGN: Serum CRP levels were determined on postoperative days 1, 3, and
      7 in patients undergoing liver resection (stratified into minor [</=2 segments],
      standard [3 or 4 segments], and extended [>/=5 segments]). Correlations were made
      with indices of PHLF (hyperbilirubinemia, coagulopathy, ascites, and
      encephalopathy), multi-organ dysfunction syndrome, sepsis, and death. SETTING:
      Division of Hepatobiliary and Transplant Surgery, Leeds Teaching Hospitals
      National Health Service Trust, England. PATIENTS: One hundred thirty-eight
      individuals who underwent liver resection. MAIN OUTCOME MEASURES: Sepsis, PHLF,
      and mortality. RESULTS: A total of 138 liver resections (39 minor, 51 standard,
      and 48 extended) were included. Median serum CRP levels on day 1 were
      significantly lower after extended liver resection (28 mg/L; range, 5-119 mg/L
      [to convert to nanomoles per liter, multiply by 9.524]) compared with standard
      resection (41 mg/L; range, 5-85 mg/L) and minor resection (51 mg/L; range, 8-203
      mg/L; chi(2) = 19; P < .001). Similar differences were observed on day 3 (chi(2)
      = 27; P < .001). Postoperative day 1 CRP levels were significantly lower in
      patients developing PHLF (hyperbilirubinemia, P = .001; ascites, P < .001;
      coagulopathy, P = .002; and encephalopathy, P < .001) or multiorgan dysfunction
      syndrome (P = .009) or who died (P = .01). Day 1 serum CRP levels and extent of
      resection were independent predictors of PHLF in multivariate analysis.
      CONCLUSION: The early dampened CRP response after major liver resection may
      reflect poor hepatic reserve that could have prognostic utility.

PMID- 18347272
TI  - Sex dimorphism in the outcome of preoperative right portal vein embolization.
AB  - HYPOTHESIS: Although studies indicate that patient sex modulates the process of
      hepatic regeneration, it remains unknown whether sex has a role in the outcome of
      preoperative right portal vein embolization (PVE). We analyzed the effects of
      patient sex on the outcome of right PVE followed by major hepatectomy. DESIGN:
      Retrospective study. SETTING: Academic research. PATIENTS: Eighty-eight patients
      (42 men and 46 women) who underwent preoperative right PVE for bile duct
      carcinoma were analyzed retrospectively. MAIN OUTCOME MEASURES: The percentage
      liver volume change, the plasma indocyanine green clearance rate, and the rate of
      postoperative hepatic failure were compared between men and women. RESULTS: The
      mean (SD) volume of the nonembolized lobe after PVE in women (323 [61] mL/m(2))
      was statistically significantly greater than that in men (287 [61] mL/m(2)) (P
      =.008). The mean (SD) ratio of the nonembolized lobe to the total liver volume
      was also statistically significantly greater in women (45.8% [5.8%]) than in men
      (42.0% [5.9%]) (P =.003). The mean (SD) indocyanine green clearance rate of the
      future liver remnant was 0.075 [0.014] in women and 0.056 [0.011] in men (P
      =.001). The incidence of postoperative hepatic failure was higher in men (12 of
      42 [28.6%]) than in women (8 of 46 [17.4%]) (P =.16). CONCLUSION: These results
      indicate that sex dimorphism can be present in the outcome of preoperative right
      PVE.

PMID- 18347273
TI  - The changing presentation of hyperparathyroidism over 3 decades.
AB  - OBJECTIVE: To analyze changes in the presentation of primary hyperparathyroidism
      over the last 3 decades. DESIGN: Retrospective review. SETTING: Tertiary referral
      center. PATIENTS: Three hundred patients undergoing parathyroidectomy for primary
      hyperparathyroidism, 100 each in the years 1985, 1995, and 2005. MAIN OUTCOME
      MEASURES: Analysis was performed based on patient age, sex, preoperative calcium
      value, duration of hypercalcemia, symptoms at presentation, and reason for
      surgical referral. RESULTS: Patients from the years 1985, 1995, and 2005 were
      similar in age and sex. Mean (SEM) preoperative calcium values decreased from
      11.8 (0.1) mg/dL in 1985 to 11.2 (0.1) mg/dL in 2005 (P < .001) (to convert
      milligrams per deciliter to millimoles per liter, multiply by 0.25). The
      proportion of patients with preoperative calcium values less than 11.0 mg/dL
      steadily rose from 10% in 1985 to 43% in 2005 (P < .001). The mean (SEM) time
      from diagnosis of hypercalcemia until surgical referral decreased from 2.5 (0.4)
      years in 1985 to 1.6 (0.2) years in 2005 (P = .08). The primary reason for
      referral has shifted toward osteoporosis (20% in 2005 vs 7% in 1985; P = .03).
      The percentage of patients diagnosed with osteoporosis or osteopenia
      preoperatively increased from 10% in 1985 to 44% in 2005 (P < .001), and the
      recognition of these conditions in men increased from 3% to 26% (P = .10).
      CONCLUSIONS: Over the last 3 decades, increased awareness of hyperparathyroidism
      and its consequences as well as the institution of screening bone densitometry
      have changed the profile of patients who are referred for surgery. Patients are
      being referred sooner, with a lesser degree of hypercalcemia and greater
      recognition of osteoporosis.

PMID- 18347274
TI  - Surgical reintervention after antireflux surgery for gastroesophageal reflux
      disease: a prospective cohort study in 130 patients.
AB  - HYPOTHESIS: Surgical reintervention after antireflux surgery for gastroesophageal
      reflux disease is required in 3% to 6% of patients. The subjective outcome after
      reintervention has been reported in several studies, but objective results after
      these subsequent operations have rarely been published. The purpose of this study
      was to assess the symptomatic and objective outcomes in patients who underwent
      subsequent operation because of recurrent reflux symptoms or troublesome
      dysphagia after primary antireflux surgery. DESIGN: Prospective cohort study.
      SETTING: University medical center. PATIENTS: Between January 1, 1994, and March
      31, 2005, 130 patients (mean [SD] age, 48.4 [14.1] years) undergoing surgical
      reintervention after antireflux surgery for gastroesophageal reflux disease were
      prospectively studied. MAIN OUTCOME MEASURES: Symptomatic outcome was determined
      by questionnaires. Esophageal manometry and 24-hour pH monitoring were performed
      to assess the objective outcome. RESULTS: A total of 144 reinterventions were
      performed in 130 patients, for recurrent reflux in 94 patients (65.3%) and for
      troublesome dysphagia in 50 patients (34.7%). Belsey Mark IV fundoplication
      through a left-sided thoracotomy was performed in 78 (54.2%) and a subsequent
      Nissen or partial fundoplication during 66 reinterventions (45.8%), including 16
      laparoscopic procedures. After a mean (SD) follow-up of 60.1 (37.2) months,
      symptoms were absent or significantly improved in 70.3% of patients and
      esophageal acid exposure was normalized in 70.2% of patients after surgery.
      Postoperative complications occurred after 14 subsequent operations (9.7%).
      CONCLUSIONS: Surgical reintervention after antireflux surgery for
      gastroesophageal reflux disease yielded good symptomatic and objective results in
      70% of patients in this prospective cohort study. Since the morbidity of this
      type of surgery is far from negligible, the expectations should be discussed in
      detail before additional operation.

PMID- 18347275
TI  - Treatment decision making in pancreatic adenocarcinoma: multidisciplinary team
      discussion with multidetector-row computed tomography.
AB  - HYPOTHESIS: Multidetector-row computed tomography reduces the frequency of use of
      other imaging methods in patients with pancreatic carcinoma. DESIGN: Validation
      cohort study. SETTING: Tertiary care public hospital. PATIENTS: Two hundred
      thirteen patients with pancreatic carcinoma. MAIN OUTCOME MEASURE: Multidetector
      row computed tomography was initially performed in patients with newly diagnosed
      pancreatic carcinoma. RESULTS: Of the 213 pancreatic carcinomas, 79 (37%) were
      classified as probably resectable, 127 (60%) as certainly unresectable, and 7
      (3%) as probably unresectable. Of 79 tumors classified as probably resectable, 68
      (86%) were found to be resectable, 7 tumors considered as probably unresectable
      were unresectable, and the remaining 127 tumors were treated nonsurgically.
      Magnetic resonance imaging was recommended in 92 patients (43%), angiography in 1
      patient (0.5%), and both endoscopic ultrasonography and endoscopic retrograde
      cholangiopancreatography in 15 patients (7%). CONCLUSIONS: Multidetector-row
      computed tomography provides reliable information for staging pancreatic
      carcinoma. Multidisciplinary team discussion along with use of this noninvasive
      technique simplifies the diagnostic strategy for pancreatic carcinoma and
      decreases the need for invasive staging methods.

PMID- 18347276
TI  - Prevalence of pain in patients 1 year after major trauma.
AB  - OBJECTIVES: To describe the prevalence of pain in a large cohort of trauma
      patients 1 year after injury and to examine personal, injury, and treatment
      factors that predict the presence of chronic pain in these patients. SETTING:
      Sixty-nine hospitals in 14 states in the United States. PATIENTS: There were 3047
      patients (10 371 weighted) aged 18 to 84 years who were admitted to the hospital
      because of acute trauma and survived to 12 months after injury. MAIN OUTCOME
      MEASURE: Pain 12 months after injury measured with the Chronic Pain Grade Scale.
      RESULTS: At 12 months after injury, 62.7% of patients reported injury-related
      pain. Most patients had pain in more than 1 body region, and the mean (SD)
      severity of pain in the last month was 5.5 (4.8) on a 10-point scale. The
      reported presence of pain varied with age and was more common in women and those
      who had untreated depression before injury. Pain at 3 months was predictive of
      both the presence and higher severity of pain at 12 months. Lower pain severity
      was reported by patients with a college education and those with no previous
      functional limitations. CONCLUSIONS: Most trauma patients have moderately severe
      pain from their injuries 1 year later. Earlier and more intensive interventions
      to treat pain in trauma patients may be needed.

PMID- 18347277
TI  - A single-institution prospective study of laparoscopic pancreatic resection.
AB  - HYPOTHESIS: Laparoscopic pancreatic resection can safely duplicate all of the
      open pancreatic procedures. DESIGN: A prospective evaluation of laparoscopic
      pancreatic resection. Surgical procedure, postoperative course, and follow-up
      data were collected. SETTING: Department of Abdominal Surgery at Haut-Leveque
      Hospital, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
      PATIENTS: Sixty patients with presumed pancreatic neoplasms. Final diagnoses were
      benign disease in 57 patients (95%) and malignant pancreatic disease in 3
      patients (5%). MAIN OUTCOME MEASURES: Complication and success rates of
      resections. RESULTS: Twenty percent of procedures were switched to open
      laparotomy. Laparoscopically successful procedures included 20 distal
      pancreatectomies with spleen preservation, 5 distal splenopancreatectomies, 16
      enucleations, 5 medial pancreatectomies, 1 pancreatoduodenectomy, and 1 total
      pancreatectomy. Postoperative death occurred in 1 patient (1.6%). The overall
      postoperative complication rate was 36%, including a 13% rate of clinical
      fistulae. In successful laparoscopic operations, the mean (SD) postoperative
      hospital stay was 12.7 (6) days. Multivariate, stepwise analysis identified
      pancreatic consistency and pancreatic resection that required anastomosis as
      independent factors of postoperative complication (P = .02 and P = .002,
      respectively). The 3 patients operated on for pancreatic malignancies were still
      alive at follow-up (median, 23 months); all patients with benign disease were
      alive at long-term follow-up. CONCLUSIONS: This series demonstrates that
      laparoscopic pancreatic resection is not only feasible but also safe. Our study
      suggests that the best indications for a laparoscopic approach are presumably
      benign pancreatic tumors not requiring pancreaticoenteric reconstruction.

PMID- 18347278
TI  - Efficacy and safety of recombinant activated factor vii in major surgical
      procedures: systematic review and meta-analysis of randomized clinical trials.
AB  - OBJECTIVE: To investigate the efficacy and safety of recombinant activated factor
      VII (rFVIIa) treatment in patients undergoing major surgical procedures. DATA
      SOURCES: Relevant studies were searched in BioMedCentral, CENTRAL, PubMed, and
      PubMed Central. STUDY SELECTION: Only randomized controlled trials on humans
      undergoing major surgery were included. Efficacy was determined as the rate of
      patients receiving allogeneic packed red blood cells; safety was assessed in
      terms of thromboembolic complications and mortality rate. DATA EXTRACTION: We
      followed the Cochrane Collaboration method for data extraction and internal
      validity procedures, as well as the Quality of Reporting of Meta-analyses
      statement. DATA SYNTHESIS: Seven randomized controlled trials met the inclusion
      criteria. Treatment with rFVIIa is associated with a reduced risk of receiving
      allogeneic packed red blood cells (odds ratio, 0.29; 95% confidence interval,
      0.10-0.80). In a subgroup analysis, only patients receiving at least 50 mug/kg of
      rFVIIa had a significant benefit (odds ratio, 0.43; 95% confidence interval, 0.23
      0.78). No differences in thromboembolic complications and mortality rates were
      observed. CONCLUSIONS: Treatment with rFVIIa is effective in reducing the rate of
      patients undergoing transfusion with allogeneic packed red blood cells. However,
      the cost-benefit ratio is favorable only in patients who need a huge number of
      packed red blood cell units. No safety concerns arise from the present study.

PMID- 18347279
TI  - Extra-gastrointestinal stromal tumor of the pancreas: case report and a review of
      the literature.
AB  - Gastrointestinal (GI) stromal tumors are mesenchymal tumors that arise from the
      GI tract. In rare cases, these tumors are found in intra-abdominal sites
      unrelated to the GI tract and are immunohistochemically similar to their GI tract
      counterparts. Primary pancreatic GI stromal tumors are very rare, with only 4
      previous cases reported.

PMID- 18347280
TI  - Image of the month. Cecal diverticulitis.

PMID- 18347281
TI  - Image of the month. Gastric juvenile polyposis (GJP) in germline SMAD4 mutation
      accompanied by gastric cancer.

PMID- 18347282
TI  - Yttrium 90 microsphere selective internal radiation treatment of hepatic
      colorectal metastases.

PMID- 18347283
TI  - Outcome of liver transplantation in older recipients.

PMID- 18347284
TI  - Executive Director's Annual Report for the American College of Surgeons, 2007.

PMID- 18347285
TI  - Heterozygosity for a single mutation in the ABCC6 gene may closely mimic PXE:
      consequences of this phenotype overlap for the definition of PXE.
AB  - OBJECTIVES: To illustrate a phenotypic overlap consisting of usual, but limited,
      or atypical manifestations of pseudoxanthoma elasticum (PXE) between heterozygous
      carriers of a single ABCC6 mutation and patients diagnosed with PXE, carriers of
      homozygous or compound heterozygous mutations. DESIGN: Evaluation for full and
      typical, incomplete, mild, or overlooked PXE during a 5-year period (2001-2005)
      based on the following 1992 expert consensus conference items: (1) yellowish
      papular skin eruption, (2) dermal elastorrhexis and mineralization of elastic
      fibers in lesional skin, and (3) angioid streaks. Testing for ABCC6 mutations was
      performed in all cases after informed consent. SETTING: French multidisciplinary
      outpatient clinic for patients with PXE. PARTICIPANTS: Patients prospectively
      referred for PXE and first-degree relatives. Main Outcome Measure Prevalence of
      PXE with a limited or atypical phenotype and manifesting heterozygosity. RESULTS:
      Ninety-four patients were diagnosed as having PXE. Fifty-eight relatives were
      also examined, and none displayed the characteristic signs of the disease.
      Despite the histoclinical items and ABCC6 genotyping, we were unable to establish
      a definite diagnosis in 5 additional referred cases, ie, to distinguish between
      PXE with a limited or atypical phenotype and heterozygosity with skin and/or
      ophthalmologic and/or cardiovascular manifestations suggestive of PXE.
      CONCLUSIONS: We assume that all categories established at the 1992 consensus
      conference correspond to PXE, but that the 5 patients reported herein also have
      PXE. Homozygous, compound heterozygous, or heterozygous individuals may fulfill
      only some of the clinical and/or histopathologic consensus criteria of PXE. They
      cannot be placed into any category. Expressivity is highly variable in carriers
      of 1 or 2 ABCC6 mutations, and the disease manifestations overlap between both
      genotypes. Physicians should thus be more cautious with respect to the prognosis
      when faced with heterozygous relatives of a patient diagnosed with undisputable
      PXE. Indeed, heterozygotes may uncommonly experience severe ophthalmologic
      complications. Whether they may also have cardiovascular complications related to
      or worsened by PXE remains to be determined.

PMID- 18347286
TI  - A Romanian population isolate with high frequency of vitiligo and associated
      autoimmune diseases.
AB  - OBJECTIVE: To characterize the epidemiology and genetics of vitiligo and
      associated autoimmune diseases in a population isolate in Romania in which there
      is a high frequency of these diseases. DESIGN: Prospective and retrospective
      ascertainment of all patients and extended families with these disorders in the
      study community. SETTING: A geographically isolated community in the mountains of
      northern Romania. Patients Fifty-one affected individuals and their close
      relatives from 35 nuclear families in an extended kindred that effectively
      constitutes the entire community population. MAIN OUTCOME MEASURES: Demographic,
      phenotypic, and genetic aspects of vitiligo and other autoimmune diseases in the
      extended kindred. RESULTS: The frequencies of vitiligo and several other
      autoimmune diseases, including autoimmune thyroid disease, adult-onset autoimmune
      diabetes mellitus, and rheumatoid arthritis, are greatly elevated. The age of
      vitiligo onset in this village is relatively delayed, suggesting that the causes
      of vitiligo in this community may be somewhat atypical. Genetic segregation
      analysis is most consistent with a single major locus recessive model, although
      incomplete penetrance and heritability suggest that other genes and nongenetic
      factors likely influence occurrence of disease in homozygotes. CONCLUSIONS: The
      high frequency of vitiligo and other autoimmune diseases in this isolated inbred
      community and an unusual aspect of the vitiligo phenotype suggest that
      susceptibility to these disorders in this "special population" may be unusual,
      likely involving a major recessive gene. Whereas disease susceptibility seems to
      involve a major genetic component, actual onset of vitiligo in genetically
      susceptible individuals seems to require exposure to environmental triggers.

PMID- 18347287
TI  - Primary erythermalgia as a sodium channelopathy: screening for SCN9A mutations:
      exclusion of a causal role of SCN10A and SCN11A.
AB  - OBJECTIVES: To elucidate the rate of missense mutations in the SCN9A gene (which
      encodes sodium channel Na(v)1.7) (OMIM 603415) among patients with primary
      erythermalgia and to examine the possibility that other sodium channels can cause
      the disease. DESIGN: Case series. SETTING: Department of Medicine, Radboud
      University Nijmegen, the Netherlands. PARTICIPANTS: Six patients with sporadic
      and 9 with unique familial primary erythermalgia. Interventions Questionnaire to
      determine clinical profile and sequencing of all coding exons from SCN9A and
      those of SCN10A (OMIM 604427) and SCN11A (OMIM 604385) in 2 selected cases with a
      clear family history of the disease. MAIN OUTCOME MEASURES: Detection of SCN9A
      mutation. RESULTS: We identified 1 patient with an SCN9A mutation. This mutation
      (I848T) has been associated with primary erythermalgia. Sequencing of 2 other
      candidate genes did not show mutations in 2 patients with familial primary
      erythermalgia. CONCLUSIONS: The Na(v)1.7 voltage-gated sodium channels are
      related to syndromes of altered nociception. We detected a low SCN9A mutation
      rate in patients with primary erythermalgia, suggesting that pain syndromes in
      the skin may have a polygenic basis.

PMID- 18347288
TI  - Between light and dark, the chimera comes out.
AB  - BACKGROUND: Chimerism, especially in the absence of sexual ambiguity, is
      extremely rare in humans. We report the case of a 6-year-old boy whose skin
      pigmentary abnormalities revealed chimerism. OBSERVATIONS: The boy had no
      remarkable previous medical history, and he had normal intelligence and
      development. On examination, we found a disorder of the skin pigmentation that
      was difficult to categorize; there was a lighter-appearing skin patch in the
      median frontal area and also on one-half of the abdominal area, with a sharp
      midline demarcation. He also had 2 lighter Blaschko-linear bands on the lower
      extremities and an indefinable mixture of lighter and darker skin on the back and
      the lateral part of the trunk. It was not possible to ascertain by means of
      clinical examination of the patient, his parents, and his brother which of the 2
      shades was his normal skin color. Because this pattern of pigmentation might be
      related to mosaicism, we determined his karyotype. We found that his lymphocytes
      had a normal number of chromosomes, half of them being either 46,XX or 46,XY. In
      contrast, his fibroblasts were exclusively XY. The chimerism was confirmed by the
      analysis of the red blood cell antigens, which revealed the presence of 2
      different populations. The characterization of the HLA haplotypes of the
      lymphocytes showed that the boy inherited 2 HLA haplotypes from his mother but
      only 1 from his father. Interestingly, the ratio of XX to XY cells was expanded
      in the T-cell subset compared with other peripheral blood mononuclear cell
      populations. CONCLUSIONS: This is an exceptional case of human chimerism revealed
      by abnormal skin pigmentation. This boy displayed 2 normal shades of skin color,
      which we suggest be termed cutis bicolor, as a result of 2 different genetic
      backgrounds. He also had immune chimerism, which challenges our current
      comprehension of antigen presentation and tolerance.

PMID- 18347289
TI  - Defective lamellar granule secretion in arthrogryposis, renal dysfunction, and
      cholestasis syndrome caused by a mutation in VPS33B.
AB  - BACKGROUND: Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is
      a rare and usually fatal metabolic autosomal recessive disorder, which has
      recently been shown to result from mutations in VPS33B located on chromosome
      15q26.1. Neurological signs and ichthyosis almost invariably accompany the
      disease. OBSERVATIONS: We assessed a consanguineous family with 2 identical twins
      affected with ARC syndrome. Complete sequencing of the VPS33B gene revealed a
      homozygous missense mutation (D234H), which segregated with the disease in the
      affected family. The mutation causes aberrant splicing, resulting in the skipping
      of exon 9 or exons 9 and 10. VPS33B encodes a homologue of the class C yeast
      vacuolar protein-sorting molecule, Vps33, which regulates soluble N
      ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein
      mediated vesicle-to-target fusion, necessary for secretion to occur. Lamellar
      granules, forming a specialized vesicular system in the epidermal upper layers,
      are usually secreted at the boundary between granular and lower cornified cell
      layers. However, ultrastructural examination of the skin in ARC syndrome revealed
      many entombed lamellar granules in the cornified cells. CONCLUSIONS: The present
      observations indicate that VPS33B deficiency results in abnormal secretion of
      lamellar granules, which underlies ichthyosis in ARC syndrome. These data
      underscore the importance of SNARE-mediated vesicle fusion during normal
      epidermal differentiation.

PMID- 18347290
TI  - X-linked ectodermal dysplasia with immunodeficiency caused by NEMO mutation:
      early recognition and diagnosis.
AB  - BACKGROUND: X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is
      described in patients with hypomorphic mutations in IKBKG (the inhibitory kappaB
      kinase gamma gene), which encodes nuclear factor kappaB essential modulator
      (NEMO). Features include hypohidrosis, dental anomalies, alopecia, and
      immunodeficiency. Boys with NEMO mutations often present with serious infections,
      but the NEMO mutations are rarely diagnosed early in infancy. Cutaneous features
      in these patients are poorly elucidated. OBSERVATIONS: A 12-week-old male infant
      presented with a recalcitrant skin eruption, intertrigo, atopiclike dermatitis,
      and erythroderma. Alopecia, frontal bossing, and periorbital wrinkling were
      present, and family history revealed incontinentia pigmenti in his mother.
      Laboratory evaluation revealed leukocytosis with eosinophilia, low IgG and IgM
      levels, and absent IgA. Flow cytometry revealed lymphocytosis with elevated
      CD3(+) and CD4(+) counts and low levels of natural killer cells. Amplification
      and sequencing of IKBKG revealed insertion of cytosine at nucleotide 1167 (1167
      1168insC) in exon 10, with frameshift mutation in the zinc-finger domain.
      Peripheral blood stem cell transplantation led to initial engraftment and
      improvement in his skin findings, but his engrafted cell counts diminished, and a
      second stem cell transplantation was planned. CONCLUSIONS: Mutations in NEMO
      should be considered in male infants with recalcitrant seborrheic or atopic
      dermatitislike eruptions and intertrigo, especially when features of ectodermal
      dysplasia are present. Early recognition and diagnosis are desirable, prior to
      the onset of manifestations of immunodeficiency.

PMID- 18347291
TI  - Self-healing collodion membrane and mild nonbullous congenital ichthyosiform
      erythroderma due to 2 novel mutations in the ALOX12B gene.
AB  - BACKGROUND: Collodion phenotype is a term applied to the condition affecting a
      newborn involving a parchmentlike membrane covering the whole body surface
      (collodion membrane). This presentation is common to several different forms of
      autosomal recessive congenital ichthyoses, including nonbullous congenital
      ichthyosiform erythroderma (NCIE), lamellar ichthyosis (LI), and harlequin
      ichthyosis (HI). Recent years have seen considerable advances in our
      understanding of the molecular basis of autosomal recessive forms of congenital
      ichthyosis. Several genetic loci have been identified for LI and NCIE.
      OBSERVATIONS: We describe the clinical and molecular features of 2 cases of self
      healing newborns of collodion phenotype developing mild NCIE. A dramatic
      improvement of the skin was observed in the first few weeks after birth in both
      cases. The molecular analysis of the ALOX12B gene demonstrated that both patients
      were compound heterozygous for previously unreported mutations. CONCLUSIONS: Both
      patients were compound heterozygous for novel ALOX12B mutations, underscoring the
      concept that mutations in at least 2 different genes, ALOX12B and TGM1, may
      result in this unusual clinical phenotype.

PMID- 18347292
TI  - Bullous sweet syndrome in a patient with t(9;22)(q34;q11)-positive chronic
      myeloid leukemia treated with the tyrosine kinase inhibitor nilotinib: interphase
      cytogenetic detection of BCR-ABL- positive lesional cells.
AB  - BACKGROUND: An association of Sweet syndrome with chronic myeloid leukemia (CML)
      has been recently observed in patients treated with tyrosine kinase inhibitors.
      OBSERVATIONS: We describe a 67-year-old patient with a 6-year history of
      Philadelphia chromosome translocation t(9;22)(q34;q11)-positive CML. The tyrosine
      kinase inhibitor AMN107 (nilotinib) kept the patient in chronic phase. After 10
      months of taking nilotinib, he developed pneumonia with septic features. Seven
      days later, bullous skin infiltrations on the upper arms and a large, painful
      bullous swelling of the right neck occurred without any evidence of a viral,
      bacterial, or fungal blood infection. Findings from histologic examination showed
      massive infiltrations of the whole dermis with neutrophil granulocytes as well as
      with monocytoid histiocytic cells. Fluorescence in situ hybridization analysis of
      paraffin-embedded tissue revealed a BCR-ABL fusion, indicating the presence of
      t(9;22)(q34;q11). The addition of oral prednisolone to an adequate antibiotic
      treatment led to rapid resolution of the cutaneous infiltrations. CONCLUSIONS:
      Skin infiltrations consistent with Sweet syndrome can occur in patients with
      septic CML during the treatment with tyrosine kinase inhibitors, including
      nilotinib. Skin infiltrations can include specific CML cells.

PMID- 18347293
TI  - A human papillomavirus-associated disease with disseminated warts, depressed cell
      mediated immunity, primary lymphedema, and anogenital dysplasia: WILD syndrome.
AB  - BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genodermatosis
      associated with infections with specific human papillomaviruses (HPVs) belonging
      to the beta genus of HPV. Patients with EV usually have a selective defect in
      cell-mediated immunity. Although skin cancer frequently develops in the sun
      exposed cutaneous lesions of patients with EV, the anogenital area is usually not
      affected by squamous cell carcinomas related to mucosal HPV types. OBSERVATIONS:
      We report the case of a patient with clinical similarities to EV who also
      presented with primary lymphedema, anogenital dysplasias, and depressed cell
      mediated immunity. Swab samples and biopsy specimens from various body sites
      collected over a 28-month period were screened by different protocols for DNA of
      the HPV groups alpha, beta, and mu/nu. Seventeen alpha-HPV types could be
      demonstrated. Interestingly, beta-HPVs (HPV-22 and HPV-23) were detectable only
      in plucked eyebrows and in 1 skin swab sample. None of the specimens from
      lesional biopsies carried beta-HPV. Consistently found alpha-HPV types included
      HPV types 6, 51, 52, 61, and 84 in the genitoanal region and HPV-57 in skin
      lesions. Histological and cytological evaluation revealed multifocal anogenital
      dysplasia and benign genital and cutaneous warts. CONCLUSIONS: To our knowledge,
      only 1 other similar case of an EV-like syndrome with impaired, cell-mediated
      immunity and primary lymphedema has been described in the literature. Based on
      the characteristic clinical and virological findings in the present case and the
      previously published case, we speculate that both patients could have a
      previously unknown syndrome that has clinical similarities to EV but notably
      differs in the associated HPV types. We suggest the acronym WILD (warts,
      immunodeficiency, lymphedema, dysplasia) to characterize this syndrome.

PMID- 18347294
TI  - "Nagashima-type" keratosis as a novel entity in the palmoplantar keratoderma
      category.
AB  - BACKGROUND: "Nagashima-type" keratosis is characterized by transgressive and
      nonprogressive palmoplantar keratoderma (PPK) with an autosomal recessive trait.
      Because its clinical manifestations are similar to but milder than those of mal
      de Meleda, it was originally described as a mild form of Meleda-type PPK. Since
      then, about 20 cases have been reported in the Japanese-language literature.
      However, to our knowledge, no cases have been reported from countries other than
      Japan, presumably because Nagashima-type PPK was not recognized as a distinct
      entity. It is essential to describe the characteristics of this disease in the
      English-language literature. OBSERVATIONS: A 17-year-old boy presented with
      transgressive, hyperhidrotic, erythematous, and hyperkeratotic lesions on his
      palms and soles that had developed when he was an infant and had progressed until
      2 to 3 years earlier. His family history revealed no similar disorders. The
      symptoms and clinical course were typical for Nagashima-type PPK. A genetic study
      was performed to search for a mutation in the SLURP1 gene, which is responsible
      for mal de Meleda, but no mutations were detected in the exon or intron sites of
      SLURP1. Conclusion The results of the present genetic study suggest that
      Nagashima-type keratosis is a novel entity of PPK and is distinct from mal de
      Meleda.

PMID- 18347295
TI  - Recessive palmoplantar keratodermas: a fertile biological hunting ground.

PMID- 18347296
TI  - Molecular genetics as a diagnostic and prognostic aid in the assessment of
      neonates with red, scaly genodermatoses: work still in progress.

PMID- 18347297
TI  - Dermatology in the postgenomic era: harnessing human variation for personalized
      medicine.

PMID- 18347298
TI  - Autoinflammatory diseases: clinical and genetic advances.
AB  - We conducted a literature review to investigate the recent advances in genetics,
      molecular biology, clinical manifestations, and therapy of 7 inherited diseases
      that are characterized by seemingly unprovoked inflammation. These
      autoinflammatory diseases include familial Mediterranean fever; tumor necrosis
      factor receptor-associated periodic syndrome; hyperimmunoglobulinemia D with
      periodic fever syndrome; pyogenic arthritis, pyoderma gangrenosum, and acne
      syndrome; and the 3 cryopyrinopathies: neonatal-onset multisystem inflammatory
      disease/chronic infantile neurologic cutaneous and arthropathy syndrome, familial
      cold autoinflammatory syndrome, and Muckle-Wells syndrome. Recent identification
      of the susceptibility genes for autoinflammatory diseases has broadened the
      clinical spectrum as well as the molecular basis of these diseases. The
      cryopyrinopathies represent a continuum of diseases associated with mutations in
      the cold-induced autoinflammatory syndrome 1 (CIAS1) gene that encodes cryopyrin.
      Cryopyrin and pyrin (protein mutated in familial Mediterranean fever) belong to
      the family of PYRIN domain-containing proteins. Pyogenic arthritis, pyoderma
      gangrenosum, and acne syndrome is associated with mutations in the gene that
      encodes for CD2-binding protein 1 (CD2BP1), which binds pyrin. Recent studies
      have shown that activation of the interleukin 1beta pathway is a common mechanism
      in the pathogenesis of autoinflammatory diseases, further unifying these
      diseases. Recent advances in genetics and molecular biology have advanced our
      understanding of the pathogenesis of autoinflammatory diseases. Understanding
      autoinflammatory diseases will further our knowledge of cutaneous as well as
      systemic inflammation. Anakinra, a recombinant human interleukin 1 receptor
      antagonist, is a promising new biologic agent for the treatment of
      cryopyrinopathies as well other autoinflammatory diseases, such as tumor necrosis
      factor receptor-associated periodic syndrome and hyperimmunoglobulinemia D with
      periodic fever syndrome.

PMID- 18347299
TI  - Time to nip "seeding trials" in the bud.

PMID- 18347300
TI  - An unusual keratotic papular eruption.

PMID- 18347301
TI  - Solitary nodule in a 3-month-old infant.

PMID- 18347302
TI  - Violaceous purpuric plaques on the lower extremity.

PMID- 18347303
TI  - An unusual case of leg ulceration--quiz case.

PMID- 18347304
TI  - MBL2 functional allelic variants and increased risk for the development of atopic
      dermatitis in Brazilian children.

PMID- 18347305
TI  - Assessment of delayed reporting of mycosis fungoides and Sezary syndrome in the
      United States.

PMID- 18347306
TI  - Linear and whorled nevoid hypermelanosis: unique clinical presentations and their
      possible association with chromosomal abnormality inv(9).

PMID- 18347307
TI  - Amelanotic melanoma in a patient with Rothmund-Thomson syndrome.

PMID- 18347308
TI  - Dermoscopy of Dowling-Degos disease of the vulva.

PMID- 18347309
TI  - Cutaneous noncaseating granulomas associated with Nijmegen breakage syndrome.

PMID- 18347310
TI  - Adnexal tumors: clinical and dermoscopic mimickers of basal cell carcinoma.

PMID- 18347312
TI  - Tuberous sclerosis complex: a tale of two genes.

PMID- 18347313
TI  - SOX1 autoantibodies: tumor markers in LEMS patients?

PMID- 18347314
TI  - Paraoxonase 1 (PON1) organophosphate hydrolysis is not reduced in ALS.
AB  - OBJECTIVE: Four recent studies report a genetic association of the paraoxonase
      locus with sporadic amyotrophic lateral sclerosis (ALS). We tested the hypothesis
      that this association correlates with functional changes in paraoxonase 1 (PON1,
      MIM 168820). METHODS: Sera from 140 ALS participants; 153 age-, race-, and sex
      matched controls; and 30 matched CSF samples were tested for paraoxonase,
      diazoxonase, and arylesterase activities. Participants with ALS were genotyped
      using tagging single nucleotide polymorphisms across the PON locus. Survival data
      and enzyme activity were correlated with genotype. RESULTS: There was a trend
      toward increased paraoxonase activity in ALS compared with controls (mean control
      paraoxonase 701.9 +/- 469.7 U/L, mean ALS 792.5 +/- 574.1 U/L; p = 0.066 after
      correction) which correlated with increased frequency of the homozygous arginine
      (RR) variant of PON1(Q192R) (p = 0.004). There was no significant difference in
      PON1 protein levels, or arylesterase or diazoxonase activities. Organophosphate
      hydrolysis rates had no effect on ALS survival. CONCLUSIONS: Contrary to
      expectations, PON1 protein, paraoxonase, diazoxonase, and arylesterase activities
      were not reduced in amyotrophic lateral sclerosis (ALS). The increase in
      PON1(R192) frequency in ALS in our study supports previous genetic susceptibility
      studies. Our findings suggest that the influence of PON1 polymorphisms on ALS
      susceptibility is not due to reduced organophosphate hydrolysis.

PMID- 18347315
TI  - Association of gait and balance disorders with age-related white matter changes:
      the LADIS study.
AB  - OBJECTIVE: In the Leukoaraiosis and Disability (LADIS) Study, 11 European centers
      are evaluating the role of age-related white matter changes (ARWMC) as an
      independent determinant of the transition to disability in the elderly (65 to 84
      years). We aimed at determining the influence of ARWMC on different objective
      measures of gait and balance. METHODS: Six hundred thirty-nine nondisabled
      individuals were prospectively enrolled and are being followed-up for 3 years.
      Subjects are graded in three standardized categories of ARWMC (mild, moderate,
      and severe) according to central MRI reading. Quantitative tests of gait and
      balance include the Short Physical Performance Battery (SPPB; range: 0 [poor] to
      12 [normal]), a timed 8-m walk, and a timed single leg stance test. RESULTS: In
      cross-sectional analysis, deficiencies in gait and balance performance were
      correlated with the severity of ARWMC (SPPB: 10.2 +/- 2.1 in the mild, 9.9 +/-
      2.0 in the moderate, 8.9 +/- 2.6 in the severe group; p < 0.001). Walking speed
      correlated with the severity of ARWMC (1.24 +/- 0.28 m/second in the mild, 1.18
      +/- 0.32 m/second in the moderate, and 1.09 +/- 0.31 m/second in the severe
      group; p < 0.001). Balance was best in individuals with mild ARWMC (single leg
      stance time: 18.9 +/- 10.8 seconds) compared with moderate and severe ARWMC (16.4
      +/- 10.8 and 13.6 +/- 11.2 seconds) (p < 0.001). Physically inactive individuals
      had a higher risk of a pathologic SPPB score (moderate vs mild ARWMC: odds ratio
      1.60, 95% CI 1.02 to 2.52; severe vs mild ARWMC: odds ratio 1.75, 95% CI 1.09 to
      2.80). CONCLUSIONS: Our findings support a strong association between the
      severity of age-related white matter changes and the severity of gait and motor
      compromise. Physical activity might have the potential to reduce the risk of
      limitations in mobility.

PMID- 18347316
TI  - Bacterial and fungal meningitis in patients with cancer.
AB  - OBJECTIVE: To analyze cases of bacterial and fungal meningitis in patients with
      cancer. METHODS: Retrospective chart review from 1993 to 2004 was performed of
      patients with cancer at our institution who had positive CSF bacterial or fungal
      culture. RESULTS: We identified 312 positive CSF cultures representing 175 unique
      presentations. Ninety-six cultures were deemed contaminants, leaving 79 cultures
      for analysis in 77 patients; 78% had prior neurosurgery. Organisms included 68%
      gram-positive cocci, 10% gram-positive bacilli, 14% gram-negative bacilli, 7%
      Cryptococcus, and 1% C. albicans. None had N. meningitidis or H. influenza. Two
      patients each had S. pneumoniae or L. monocytogenes. Five percent of
      presentations demonstrated the triad of fever, nuchal rigidity, and mental status
      changes. Seventy-five percent of presentations demonstrated CSF pleocytosis (> or
      = 10). Median CSF WBC count was 74 cells/mm(3). CSF protein was elevated and
      glucose was depressed in 71%. In neutropenic patients (n = 6), 4 had 0 to 1 CSF
      WBC/mm(3), and 2 had normal CSF. VP shunt infections were more likely to present
      with mental status changes. Thirty day mortality was 13%. CONCLUSIONS: Patients
      with cancer do not manifest symptoms of meningitis as often as patients without
      cancer and display a very different set of CSF organisms compared to a general
      population. The CSF inflammatory response is muted in patients with cancer with
      meningitis. Most patients with cancer with meningitis have had prior
      neurosurgery. Additionally, the organisms causing meningitis in the cancer
      population have shifted over time, with a decline in the organisms which
      typically infect immunocompromised hosts and an increase in gram-positive
      infections.

PMID- 18347317
TI  - Diffusion tensor imaging of acute mild traumatic brain injury in adolescents.
AB  - BACKGROUND: Despite normal CT imaging and neurologic functioning, many
      individuals report postconcussion symptoms following mild traumatic brain injury
      (MTBI). This dissociation has been enigmatic for clinicians and investigators.
      METHODS: Diffusion tensor imaging tractography of the corpus callosum was
      performed in 10 adolescents (14 to 19 years of age) with MTBI 1 to 6 days
      postinjury with Glasgow Coma Scale score of 15 and negative CT, and 10 age- and
      gender-equivalent uninjured controls. Subjects were administered the Rivermead
      Post Concussion Symptoms Questionnaire and the Brief Symptom Inventory to assess
      self-reported cognitive, affective, and somatic symptoms. RESULTS: The MTBI group
      demonstrated increased fractional anisotropy and decreased apparent diffusion
      coefficient and radial diffusivity, and more intense postconcussion symptoms and
      emotional distress compared to the control group. Increased fractional anisotropy
      and decreased radial diffusivity were correlated with severity of postconcussion
      symptoms in the MTBI group, but not in the control group. CONCLUSIONS: In
      adolescents with mild traumatic brain injury (MTBI) with Glasgow Coma Scale score
      of 15 and negative CT, diffusion tensor imaging (DTI) performed within 6 days
      postinjury showed increased fractional anisotropy and decreased diffusivity
      suggestive of cytotoxic edema. Advanced MRI-based DTI methods may enhance our
      understanding of the neuropathology of TBI, including MTBI. Additionally, DTI may
      prove more sensitive than conventional imaging methods in detecting subtle, but
      clinically meaningful, changes following MTBI and may be critical in refining
      MTBI diagnosis, prognosis, and management.

PMID- 18347318
TI  - The pupillary light reflex pathway: cytoarchitectonic probabilistic maps in
      hemianopic patients.
AB  - OBJECTIVE: The anatomy of the human pupillary light reflex (PLR) pathway is a
      matter of debate. The aim of this study was twofold: namely, to investigate the
      association of a relative afferent pupillary defect (RAPD) in acquired
      suprageniculate lesions with the location and extent of the cerebral lesions.
      Further, we suggest a new strategy of lesion analysis by combining established
      techniques with the stereotaxic probabilistic cytoarchitectonic atlas developed
      by the Julich group. METHODS: Twenty-three patients with homonymous visual field
      defects participated in this study. The RAPD was quantified clinically by two
      independent examiners with graded neutral density filters (swinging flashlight
      test). Using MRI in each individual, cerebral regions commonly affected in
      patients with a RAPD but spared in patients without a RAPD were determined and
      subsequently assessed by using cytoarchitectonic probabilistic maps. RESULTS: A
      RAPD was present in 10/23 patients. Comparison of patients showing a RAPD vs
      those not showing a RAPD revealed that a region including the course of the optic
      radiation at its early beginning in the temporal white matter is commonly
      associated with a RAPD. CONCLUSIONS: It was demonstrated that the pupillary light
      reflex (PLR) depends on the input of suprageniculate neurons, thus supporting the
      involvement of a cortical pathway also. The site of integration of cortical
      signals in relation to the PLR into the pupillomotor pathway may be located
      suprageniculately in the vicinity of the lateral geniculate nucleus. Moreover,
      the suggested combination of established lesion analysis techniques with the
      probabilistic cytoarchitectonic atlas turned out to be a very helpful
      amelioration of stroke data analyses.

PMID- 18347319
TI  - Metabotropic glutamate receptors: synaptic modulators and therapeutic targets for
      neurologic disease.

PMID- 18347320
TI  - Weir Mitchell's 1859 demonstration of "a peculiar contraction" produced by a
      percussion hammer.
AB  - BACKGROUND: The 1875 publications of Erb and Westphal brought widespread
      attention to the percussion of muscle stretch reflexes. Although the maneuver may
      have been observed before 1875, there is little concrete evidence of this.
      OBJECTIVES: To bring to light an early report of percussion eliciting the muscle
      stretch response. METHODS: While studying the Weir Mitchell papers (Philadelphia
      College of Physicians), the author came across an early report of the maneuver.
      RESULTS: The 531-word 1859 report, published in the Proceedings of the Academy of
      Natural Sciences of Philadelphia, was written by a pro tem reporter who observed
      Mitchell's demonstration of the phenomenon. The other attendees, including Dr.
      William Hammond, were so well aware of the phenomena that Dr. Mitchell "did not
      consider it necessary to describe them more fully." Mitchell viewed the response
      as muscular in nature and the relationship between this response and disease was
      not explored in the report. CONCLUSIONS: This 1859 report preceded the Erb and
      Westphal publications by nearly two decades. It is perhaps the first concrete
      proof that neurologists were observing this phenomenon as early as the mid-1800s.
      Mitchell viewed the phenomenon as a local muscle response. While the concepts
      that later allowed Erb to correctly interpret the phenomenon as a reflex arc were
      already in place, Mitchell did not synthesize these concepts.

PMID- 18347321
TI  - Human herpesvirus-6 variant A encephalomyelitis.

PMID- 18347322
TI  - Uniparental disomy of chromosome 1 causing concurrent Charcot-Marie-Tooth and
      Gaucher disease Type 3.

PMID- 18347323
TI  - "Swiss cheese-like" brain due to Lactobacillus rhamnosus.

PMID- 18347324
TI  - Tracheostomy can fatally exacerbate sleep-disordered breathing in multiple system
      atrophy.

PMID- 18347325
TI  - Using ChIP-chip technology to reveal common principles of transcriptional
      repression in normal and cancer cells.
AB  - We compared 12 different cell populations, including embryonic stem cells before
      and during differentiation into embryoid bodies as well as various types of
      normal and tumor cells to determine if pluripotent versus differentiated cell
      types use different mechanisms to establish their transcriptome. We first
      identified genes that were not expressed in the 12 different cell populations and
      then determined which of them were regulated by histone methylation, DNA
      methylation, at the step of productive elongation, or by the inability to
      establish a preinitiation complex. For these experiments, we performed chromatin
      immunoprecipitation using antibodies to H3me3K27, H3me3K9, 5-methyl-cytosine, and
      POLR2A. We found that (1) the percentage of low expressed genes bound by POLR2A,
      H3me3K27, H3me3K9, or 5-methyl-cytosine is similar in all 12 cell types,
      regardless of differentiation or neoplastic state; (2) a gene is generally
      repressed by only one mechanism; and (3) distinct classes of genes are repressed
      by certain mechanisms. We further characterized two transitioning cell
      populations, 3T3 cells progressing from G0/G1 into S phase and mES cells
      differentiating into embryoid bodies. We found that the transient regulation
      through the cell cycle was achieved predominantly by changes in the recruitment
      of the general transcriptional machinery or by post-POLR2A recruitment
      mechanisms. In contrast, changes in chromatin silencing were critical for the
      permanent changes in gene expression in cells undergoing differentiation.

PMID- 18347326
TI  - De novo search for non-coding RNA genes in the AT-rich genome of Dictyostelium
      discoideum: performance of Markov-dependent genome feature scoring.
AB  - Genome data are increasingly important in the computational identification of
      novel regulatory non-coding RNAs (ncRNAs). However, most ncRNA gene-finders are
      either specialized to well-characterized ncRNA gene families or require
      comparisons of closely related genomes. We developed a method for de novo
      screening for ncRNA genes with a nucleotide composition that stands out against
      the background genome based on a partial sum process. We compared the performance
      when assuming independent and first-order Markov-dependent nucleotides,
      respectively, and used Karlin-Altschul and Karlin-Dembo statistics to evaluate
      the significance of hits. We hypothesized that a first-order Markov-dependent
      process might have better power to detect ncRNA genes since nearest-neighbor
      models have been shown to be successful in predicting RNA structures. A model
      based on a first-order partial sum process (analyzing overlapping dinucleotides)
      had better sensitivity and specificity than a zeroth-order model when applied to
      the AT-rich genome of the amoeba Dictyostelium discoideum. In this genome, we
      detected 94% of previously known ncRNA genes (at this sensitivity, the false
      positive rate was estimated to be 25% in a simulated background). The predictions
      were further refined by clustering candidate genes according to sequence
      similarity and/or searching for an ncRNA-associated upstream element. We
      experimentally verified six out of 10 tested ncRNA gene predictions. We conclude
      that higher-order models, in combination with other information, are useful for
      identification of novel ncRNA gene families in single-genome analysis of D.
      discoideum. Our generalizable approach extends the range of genomic data that can
      be searched for novel ncRNA genes using well-grounded statistical methods.

PMID- 18347327
TI  - A gene expression network model of type 2 diabetes links cell cycle regulation in
      islets with diabetes susceptibility.
AB  - Insulin resistance is necessary but not sufficient for the development of type 2
      diabetes. Diabetes results when pancreatic beta-cells fail to compensate for
      insulin resistance by increasing insulin production through an expansion of beta
      cell mass or increased insulin secretion. Communication between insulin target
      tissues and beta-cells may initiate this compensatory response. Correlated
      changes in gene expression between tissues can provide evidence for such
      intercellular communication. We profiled gene expression in six tissues of mice
      from an obesity-induced diabetes-resistant and a diabetes-susceptible strain
      before and after the onset of diabetes. We studied the correlation structure of
      mRNA abundance and identified 105 co-expression gene modules. We provide an
      interactive gene network model showing the correlation structure between the
      expression modules within and among the six tissues. This resource also provides
      a searchable database of gene expression profiles for all genes in six tissues in
      lean and obese diabetes-resistant and diabetes-susceptible mice, at 4 and 10 wk
      of age. A cell cycle regulatory module in islets predicts diabetes
      susceptibility. The module predicts islet replication; we found a strong
      correlation between (2)H(2)O incorporation into islet DNA in vivo and the
      expression pattern of the cell cycle module. This pattern is highly correlated
      with that of several individual genes in insulin target tissues, including Igf2,
      which has been shown to promote beta-cell proliferation, suggesting that these
      genes may provide a link between insulin resistance and beta-cell proliferation.

PMID- 18347328
TI  - Chemokine receptor CXCR3 and its ligands CXCL9 and CXCL10 are required for the
      development of murine cerebral malaria.
AB  - Cerebral malaria is a significant cause of global mortality, causing an estimated
      two million deaths per year, mainly in children. The pathogenesis of this disease
      remains incompletely understood. Chemokines have been implicated in the
      development of cerebral malaria, and the IFN-inducible CXCR3 chemokine ligand IP
      10 (CXCL10) was recently found to be the only serum biomarker that predicted
      cerebral malaria mortality in Ghanaian children. We show that the CXCR3 chemokine
      ligands IP-10 and Mig (CXCL9) were highly induced in the brains of mice with
      murine cerebral malaria caused by Plasmodium berghei ANKA. Mice deficient in
      CXCR3 were markedly protected against cerebral malaria and had far fewer T cells
      in the brain compared with wild-type mice. In competitive transfer experiments,
      CXCR3-deficient CD8(+) T cells were 7-fold less efficient at migrating into the
      infected brains than wild-type CD8(+) T cells. Adoptive transfer of wild-type
      CD8(+) effector T cells restored susceptibility of CXCR3-deficient mice to
      cerebral malaria and also restored brain proinflammatory cytokine and chemokine
      production and recruitment of T cells, independent of CXCR3. Mice deficient in IP
      10 or Mig were both partially protected against cerebral malaria mortality when
      infected with P. berghei ANKA. Brain immunohistochemistry revealed Mig staining
      of endothelial cells, whereas IP-10 staining was mainly found in neurons. These
      data demonstrate that CXCR3 on CD8(+) T cells is required for T cell recruitment
      into the brain and the development of murine cerebral malaria and suggest that
      the CXCR3 ligands Mig and IP-10 play distinct, nonredundant roles in the
      pathogenesis of this disease.

PMID- 18347329
TI  - Gene expression-based screening identifies microtubule inhibitors as inducers of
      PGC-1alpha and oxidative phosphorylation.
AB  - The transcriptional coactivator PGC-1alpha is a potent regulator of several
      metabolic pathways, including, in particular, the activation of oxidative
      phosphorylation and mitochondrial biogenesis. Recent evidence suggests that
      increasing PGC-1alpha activity may have beneficial effects in various conditions,
      including muscular dystrophy, diabetes, and neurodegenerative diseases. We
      describe here a high-throughput screen to identify small molecules that induce
      PGC-1alpha expression in skeletal muscle cells. A number of drug classes are
      identified, including glucocorticoids, microtubule inhibitors, and protein
      synthesis inhibitors. These drugs induce PGC-1alpha mRNA, and the expression of a
      number of genes known to be regulated by PGC-1alpha. No induction of these target
      genes is seen in PGC-1alpha -/- cells, demonstrating that the drugs act through
      PGC-1alpha. These data demonstrate the feasibility of high-throughput screening
      for inducers of PGC-1alpha. Moreover, the data identify microtubule inhibitors
      and protein synthesis inhibitors as modulators of PGC-1alpha and oxidative
      phosphorylation.

PMID- 18347330
TI  - Monolayer purification: a rapid method for isolating protein complexes for single
      particle electron microscopy.
AB  - Visualizing macromolecular complexes by single-particle electron microscopy (EM)
      entails stringent biochemical purification, specimen preparation, low-dose
      imaging, and 3D image reconstruction. Here, we introduce the "monolayer
      purification" method, which employs nickel-nitrilotriacetic acid (Ni-NTA)
      functionalized lipids for simultaneously purifying His-tagged complexes directly
      from cell lysates while producing specimens suitable for single-particle EM. The
      method was established by using monolayers containing Ni-NTA lipid to
      specifically adsorb His-tagged transferrin-transferrin receptor (Tf-TfR)
      complexes from insect and mammalian cell extracts. The specificity and
      sensitivity of the method could be improved by adding imidazole to the extracts.
      The monolayer-purified Tf-TfR samples could be vitrified and used to calculate a
      3D reconstruction of the complex. Monolayer purification was then used to rapidly
      isolate ribosomal complexes from bacteria by overexpressing a single His-tagged
      ribosomal subunit. The resulting monolayer samples allowed calculation of a cryo
      EM 3D reconstruction of the Escherichia coli 50S ribosomal subunit.

PMID- 18347331
TI  - Ischemic preconditioning blocks BAD translocation, Bcl-xL cleavage, and large
      channel activity in mitochondria of postischemic hippocampal neurons.
AB  - Transient forebrain or global ischemia induces delayed neuronal death in
      vulnerable CA1 pyramidal cells with many features of apoptosis. A brief period of
      ischemia, i.e., ischemic preconditioning, affords robust protection of CA1
      neurons against a subsequent more prolonged ischemic challenge. Here we show that
      preconditioning acts via PI3K/Akt signaling to block the ischemia-induced cascade
      involving mitochondrial translocation of Bad, assembly of Bad with Bcl-x(L),
      cleavage of Bcl-x(L) to form its prodeath fragment, DeltaN-Bcl-x(L), activation
      of large-conductance channels in the mitochondrial outer membrane, mitochondrial
      release of cytochrome c and Smac/DIABLO (second mitochondria-derived activator of
      caspases/direct IAP-binding protein with low pI), caspase activation, and
      neuronal death. These findings show how preconditioning acts to prevent the
      release of cytochrome c and Smac/DIABLO from mitochondria and to preserve the
      integrity of the mitochondrial membrane. The specific PI3K inhibitor LY294002
      administered in vivo 1 h before or immediately after ischemia or up to 120 h
      later significantly reverses preconditioning-induced protection, indicating a
      requirement for sustained PI3K signaling in ischemic tolerance. These findings
      implicate PI3K/Akt signaling in maintenance of the integrity of the mitochondrial
      outer membrane.

PMID- 18347332
TI  - Surprising migration and population size dynamics in ancient Iberian brown bears
      (Ursus arctos).
AB  - The endangered brown bear populations (Ursus arctos) in Iberia have been
      suggested to be the last fragments of the brown bear population that served as
      recolonization stock for large parts of Europe during the Pleistocene.
      Conservation efforts are intense, and results are closely monitored. However, the
      efforts are based on the assumption that the Iberian bears are a unique unit that
      has evolved locally for an extended period. We have sequenced mitochondrial DNA
      (mtDNA) from ancient Iberian bear remains and analyzed them as a serial dataset,
      monitoring changes in diversity and occurrence of European haplogroups over time.
      Using these data, we show that the Iberian bear population has experienced a
      dynamic, recent evolutionary history. Not only has the population undergone
      mitochondrial gene flow from other European brown bears, but the effective
      population size also has fluctuated substantially. We conclude that the Iberian
      bear population has been a fluid evolutionary unit, developed by gene flow from
      other populations and population bottlenecks, far from being in genetic
      equilibrium or isolated from other brown bear populations. Thus, the current
      situation is highly unusual and the population may in fact be isolated for the
      first time in its history.

PMID- 18347333
TI  - Myosin V and Kinesin act as tethers to enhance each others' processivity.
AB  - Organelle transport to the periphery of the cell involves coordinated transport
      between the processive motors kinesin and myosin V. Long-range transport takes
      place on microtubule tracks, whereas final delivery involves shorter actin-based
      movements. The concept that motors only function on their appropriate track
      required further investigation with the recent observation that myosin V
      undergoes a diffusional search on microtubules. Here we show, using single
      molecule techniques, that a functional consequence of myosin V's diffusion on
      microtubules is a significant enhancement of the processive run length of kinesin
      when both motors are present on the same cargo. The degree of run length
      enhancement correlated with the net positive charge in loop 2 of myosin V. On
      actin, myosin V also undergoes longer processive runs when kinesin is present on
      the same cargo. The process that causes run length enhancement on both
      cytoskeletal tracks is electrostatic. We propose that one motor acts as a tether
      for the other and prevents its diffusion away from the track, thus allowing more
      steps to be taken before dissociation. The resulting run length enhancement
      likely contributes to the successful delivery of cargo in the cell.

PMID- 18347334
TI  - Linking Notch signaling to ischemic stroke.
AB  - Vascular smooth muscle cells (SMCs) have been implicated in the pathophysiology
      of stroke, the third most common cause of death and the leading cause of long
      term neurological disability in the world. However, there is little insight into
      the underlying cellular pathways that link SMC function to brain ischemia
      susceptibility. Using a hitherto uncharacterized knockout mouse model of Notch 3,
      a Notch signaling receptor paralogue highly expressed in vascular SMCs, we
      uncover a striking susceptibility to ischemic stroke upon challenge. Cellular and
      molecular analyses of vascular SMCs derived from these animals associate Notch 3
      activity to the expression of specific gene targets, whereas genetic rescue
      experiments unambiguously link Notch 3 function in vessels to the ischemic
      phenotype.

PMID- 18347335
TI  - Increasing morphological complexity in multiple parallel lineages of the
      Crustacea.
AB  - The prospect of finding macroevolutionary trends and rules in the history of life
      is tremendously appealing, but very few pervasive trends have been found. Here,
      we demonstrate a parallel increase in the morphological complexity of most of the
      deep lineages within a major clade. We focus on the Crustacea, measuring the
      morphological differentiation of limbs. First, we show a clear trend of
      increasing complexity among 66 free-living, ordinal-level taxa from the
      Phanerozoic fossil record. We next demonstrate that this trend is pervasive,
      occurring in 10 or 11 of 12 matched-pair comparisons (across five morphological
      diversity indices) between extinct Paleozoic and related Recent taxa. This
      clearly differentiates the pattern from the effects of lineage sorting.
      Furthermore, newly appearing taxa tend to have had more types of limbs and a
      higher degree of limb differentiation than the contemporaneous average, whereas
      those going extinct showed higher-than-average limb redundancy. Patterns of
      contemporary species diversity partially reflect the paleontological trend. These
      results provide a rare demonstration of a large-scale and probably driven trend
      occurring across multiple independent lineages and influencing both the form and
      number of species through deep time and in the present day.

PMID- 18347336
TI  - Activation of Trk neurotrophin receptors by glucocorticoids provides a
      neuroprotective effect.
AB  - Glucocorticoids (GCs) display both protective and destructive effects in the
      nervous system. In excess, GCs produce neuronal damage after stress or brain
      injury; however, the neuroprotective effects of adrenal steroids also have been
      reported. The mechanisms that account for the positive actions are not well
      understood. Here we report that GCs can selectively activate Trk receptor
      tyrosine kinases after in vivo administration in the brain and in cultures of
      hippocampal and cortical neurons. Trk receptors are normally activated by
      neurotrophins, such as NGF and brain-derived neurotrophic factor, but the
      activation of Trk receptors by GCs does not depend on increased production of
      neurotrophins. Other tyrosine kinase receptors, such as EGF and FGF receptors,
      were not activated by GCs. The ability of GCs to increase Trk receptor activity
      resulted in the neuroprotection of neurons deprived of trophic support and could
      be modulated by steroid-converting enzymes. Pharmacological and shRNA experiments
      indicate that Trk receptor activation by GCs depends on a genomic action of the
      GC receptor. The ability of GCs to promote Trk receptor activity represents a
      molecular mechanism that integrates the actions of GCs and neurotrophins.

PMID- 18347337
TI  - Close correspondence between quantitative- and molecular-genetic divergence times
      for Neandertals and modern humans.
AB  - Recent research has shown that genetic drift may have produced many cranial
      differences between Neandertals and modern humans. If this is the case, then it
      should be possible to estimate population genetic parameters from Neandertal and
      modern human cranial measurements in a manner analogous to how estimates are made
      from DNA sequences. Building on previous work in evolutionary quantitative
      genetics and on microsatellites, we present a divergence time estimator for
      neutrally evolving morphological measurements. We then apply this estimator to 37
      standard cranial measurements collected on 2,524 modern humans from 30 globally
      distributed populations and 20 Neandertal specimens. We calculate that the
      lineages leading to Neandertals and modern humans split approximately 311,000
      (95% C.I.: 182,000 to 466,000) or 435,000 (95% C.I.: 308,000 to 592,000) years
      ago, depending on assumptions about changes in within-population variation. These
      dates are quite similar to those recently derived from ancient Neandertal and
      extant human DNA sequences. Close correspondence between cranial and DNA-sequence
      results implies that both datasets largely, although not necessarily exclusively,
      reflect neutral divergence, causing them to track population history or phylogeny
      rather than the action of diversifying natural selection. The cranial dataset
      covers only aspects of cranial anatomy that can be readily quantified with
      standard osteometric tools, so future research will be needed to determine
      whether these results are representative. Nonetheless, for the measurements we
      consider here, we find no conflict between molecules and morphology.

PMID- 18347338
TI  - Repetition suppression of ventromedial prefrontal activity during judgments of
      self and others.
AB  - One useful strategy for inferring others' mental states (i.e., mentalizing) may
      be to use one's own thoughts, feelings, and desires as a proxy for those of other
      people. Such self-referential accounts of social cognition are supported by
      recent neuroimaging observations that a single brain region, ventromedial
      prefrontal cortex (vMPFC), is engaged both by tasks that require introspections
      about self and by tasks that require inferences about the minds of others
      perceived to be similar to self. To test whether people automatically refer to
      their own mental states when considering those of a similar other, we examined
      repetition-related suppression of vMPFC response during self-reflections that
      followed either an initial reflection about self or a judgment of another person.
      Consistent with the hypothesis that perceivers spontaneously engage in self
      referential processing when mentalizing about particular individuals, vMPFC
      response was suppressed when self-reflections followed either an initial
      reflection about self or a judgment of a similar, but not a dissimilar, other.
      These results suggest that thinking about the mind of another person may rely
      importantly on reference to one's own mental characteristics.

PMID- 18347339
TI  - Increased amphetamine-induced hyperactivity and reward in mice overexpressing the
      dopamine transporter.
AB  - The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic
      signaling wherein it controls both the spatial and temporal actions of dopamine.
      Here we evaluated the behavioral and neurochemical consequences of increased DAT
      function by generating DAT transgenic mice (DAT-tg) that overexpress the
      transporter. These mice were generated by pronuclear injection of a bacterial
      artificial chromosome containing the mouse DAT locus, yielding an anatomical
      expression pattern of DAT-tg identical to WT. In DAT-tg mice there is a 3-fold
      increase in the levels of total and membrane-expressed DAT, but synaptic plasma
      membrane fractions of DAT-tg mice show only a 30% increase in transporter levels.
      Functional studies reveal that in the DAT-tg animals there is a 50% increase in
      the rate of dopamine (DA) uptake resulting in extracellular levels of DA that are
      decreased by approximately 40%. Behaviorally, DAT-tg animals display similar
      locomotor stimulation when treated with DAT blockers such as GBR12909,
      methylphenidate, and cocaine. However, these mice demonstrate markedly increased
      locomotor responses to amphetamine compared with WT animals. Furthermore,
      compared with controls, there is a 3-fold greater increase in the amount of DA
      released by amphetamine in DAT-tg mice that correlates with the 3-fold increase
      in protein expression. Finally, DAT-tg animals show reduced operant responding
      for natural reward while displaying preference for amphetamine at much lower
      doses (0.2 and 0.5 mg/kg) than WT mice (2 mg/kg). These results suggest that
      overexpression of DAT leads to a marked increase in sensitivity to psychomotor
      and rewarding properties of amphetamine.

PMID- 18347340
TI  - Tug-of-war as a cooperative mechanism for bidirectional cargo transport by
      molecular motors.
AB  - Intracellular transport is based on molecular motors that pull cargos along
      cytoskeletal filaments. One motor species always moves in one direction, e.g.,
      conventional kinesin moves to the microtubule plus end, whereas cytoplasmic
      dynein moves to the microtubule minus end. However, many cellular cargoes are
      observed to move bidirectionally, involving both plus- and minus-end-directed
      motors. The presumably simplest mechanism for such bidirectional transport is
      provided by a tug-of-war between the two motor species. This mechanism is studied
      theoretically using the load-dependent transport properties of individual motors
      as measured in single-molecule experiments. In contrast to previous expectations,
      such a tug-of-war is found to be highly cooperative and to exhibit seven
      different motility regimes depending on the precise values of the single motor
      parameters. The sensitivity of the transport process to small parameter changes
      can be used by the cell to regulate its cargo traffic.

PMID- 18347341
TI  - PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects
      cells from necrosis.
AB  - Cell adaptation to changes in oxygen (O(2)) availability is controlled by two
      subfamilies of O(2)-dependent enzymes: the hypoxia inducible factor (HIF)-prolyl
      and asparaginyl hydroxylases [prolyl hydroxylases domain (PHDs) and factor
      inhibiting HIF (FIH)]. These oxygen sensors regulate the activity of the HIF, a
      transcriptional complex central in O(2) homeostasis. In well oxygenated cells,
      PHDs hydroxylate the HIFalpha subunits, thereby targeting them for proteasomal
      degradation. In contrast, acute hypoxia inhibits PHDs, leading to HIFalpha
      stabilisation. However, here we show that chronic hypoxia induces
      HIF1/2alpha"desensitization" in cellulo and in mice. At the basis of this general
      adaptative mechanism, we demonstrate that chronic hypoxia not only increases the
      pool of PHDs but also overactivates the three PHD isoforms. This overactivation
      appears to be mediated by an increase in intracellular O(2) availability
      consequent to the inhibition of mitochondrial respiration. By using in cellulo
      and in vivo siRNA, we found that the PHDs are the key enzymes triggering HIFalpha
      desensitization, a feedback mechanism required to protect cells against necrotic
      cell death and thus to adapt them across a chronic hypoxia. Hence, PHDs serve as
      dual enzymes, for which inactivation and later overactivation is necessary for
      cell survival in acute or chronic hypoxia, respectively.

PMID- 18347342
TI  - Light deprivation damages monoamine neurons and produces a depressive behavioral
      phenotype in rats.
AB  - Light is an important environmental factor for regulation of mood. There is a
      high frequency of seasonal affective disorder in high latitudes where light
      exposure is limited, and bright light therapy is a successful antidepressant
      treatment. We recently showed that rats kept for 6 weeks in constant darkness
      (DD) have anatomical and behavioral features similar to depressed patients,
      including dysregulation of circadian sleep-waking rhythms and impairment of the
      noradrenergic (NA)-locus coeruleus (LC) system. Here, we analyzed the cell
      viability of neural systems related to the pathophysiology of depression after
      DD, including NA-LC, serotoninergic-raphe nuclei and dopaminergic-ventral
      tegmental area neurons, and evaluated the depressive behavioral profile of light
      deprived rats. We found increased apoptosis in the three aminergic systems
      analyzed when compared with animals maintained for 6 weeks in 12:12 light-dark
      conditions. The most apoptosis was observed in NA-LC neurons, associated with a
      significant decrease in the number of cortical NA boutons. Behaviorally, DD
      induced a depression-like condition as measured by increased immobility in a
      forced swim test (FST). DD did not appear to be stressful (no effect on adrenal
      or body weights) but may have sensitized responses to subsequent stressors
      (increased fecal number during the FST). We also found that the antidepressant
      desipramine decreases these neural and behavioral effects of light deprivation.
      These findings indicate that DD induces neural damage in monoamine brain systems
      and this damage is associated with a depressive behavioral phenotype. Our results
      suggest a mechanism whereby prolonged limited light intensity could negatively
      impact mood.

PMID- 18347343
TI  - HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that
      reverses lupus in anti-CD3 conditioning regimen.
AB  - In allogeneic hematopoietic cell transplantation (HCT), donor T cell-mediated
      graft versus host leukemia (GVL) and graft versus autoimmune (GVA) activity play
      critical roles in treatment of hematological malignancies and refractory
      autoimmune diseases. However, graft versus host disease (GVHD), which sometimes
      can be fatal, remains a major obstacle in classical HCT, where recipients are
      conditioned with total body irradiation or high-dose chemotherapy. We previously
      reported that anti-CD3 conditioning allows donor CD8(+) T cells to facilitate
      engraftment and mediate GVL without causing GVHD. However, the clinical
      application of this radiation-free and GVHD preventative conditioning regimen is
      hindered by the cytokine storm syndrome triggered by anti-CD3 and the high-dose
      donor bone marrow (BM) cells required for induction of chimerism. Histone
      deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) are
      known to induce apoptosis of cancer cells and reduce production of
      proinflammatory cytokines by nonmalignant cells. Here, we report that SAHA
      inhibits the proliferative and cytotoxic activity of anti-CD3-activated T cells.
      Administration of low-dose SAHA reduces cytokine production and ameliorates the
      cytokine storm syndrome triggered by anti-CD3. Conditioning with anti-CD3 and
      SAHA allows induction of chimerism with lower doses of donor BM cells in old
      nonautoimmune and autoimmune lupus mice. In addition, conditioning with anti-CD3
      and SAHA allows donor CD8(+) T cell-mediated GVA activity to reverse lupus
      glomerulonephritis without causing GVHD. These results indicate that conditioning
      with anti-CD3 and HDAC inhibitors represent a radiation-free and GVHD
      preventative regimen with clinical application potential.

PMID- 18347344
TI  - Active tails enhance arboreal acrobatics in geckos.
AB  - Geckos are nature's elite climbers. Their remarkable climbing feats have been
      attributed to specialized feet with hairy toes that uncurl and peel in
      milliseconds. Here, we report that the secret to the gecko's arboreal acrobatics
      includes an active tail. We examine the tail's role during rapid climbing, aerial
      descent, and gliding. We show that a gecko's tail functions as an emergency fifth
      leg to prevent falling during rapid climbing. A response initiated by slipping
      causes the tail tip to push against the vertical surface, thereby preventing
      pitch-back of the head and upper body. When pitch-back cannot be prevented,
      geckos avoid falling by placing their tail in a posture similar to a bicycle's
      kickstand. Should a gecko fall with its back to the ground, a swing of its tail
      induces the most rapid, zero-angular momentum air-righting response yet measured.
      Once righted to a sprawled gliding posture, circular tail movements control yaw
      and pitch as the gecko descends. Our results suggest that large, active tails can
      function as effective control appendages. These results have provided biological
      inspiration for the design of an active tail on a climbing robot, and we
      anticipate their use in small, unmanned gliding vehicles and multisegment
      spacecraft.

PMID- 18347345
TI  - Chemical transmission between dopaminergic neuron pairs.
AB  - Midbrain dopaminergic (DAergic) neurons play a major regulatory role in in goal
      directed behavior and reinforcement learning. DAergic neuron activity, and
      therefore spatiotemporal properties of dopamine release, precisely encodes reward
      signals. Neuronal activity is shaped both by external afferences and local
      interactions (chemical and electrical transmissions). Numerous hints suggest the
      existence of chemical interactions between DAergic neurons, but direct evidence
      and characterization are still lacking. Here, we show, using dual patch-clamp
      recordings in rat brain slices, a widespread bidirectional chemical transmission
      between DAergic neuron pairs. Hyperpolarizing postsynaptic potentials were
      partially mediated by D2-like receptors, and entirely resulted from the
      inhibition of the hyperpolarization-activated depolarizing current (Ih). These
      results constitute the first evidence in paired recordings of a chemical
      transmission relying on conductance decrease in mammals. In addition, we show
      that chemical transmission and electrical synapses frequently coexist within the
      same neuron pair and dynamically interact to shape DAergic neuron activity.

PMID- 18347346
TI  - Systematic review: the effects of growth hormone on athletic performance.
AB  - BACKGROUND: Human growth hormone is reportedly used to enhance athletic
      performance, although its safety and efficacy for this purpose are poorly
      understood. PURPOSE: To evaluate evidence about the effects of growth hormone on
      athletic performance in physically fit, young individuals. DATA SOURCES: MEDLINE,
      EMBASE, SPORTDiscus, and Cochrane Collaboration databases were searched for
      English-language studies published between January 1966 and October 2007. STUDY
      SELECTION: Randomized, controlled trials that compared growth hormone treatment
      with no growth hormone treatment in community-dwelling healthy participants
      between 13 and 45 years of age. DATA EXTRACTION: 2 authors independently reviewed
      articles and abstracted data. DATA SYNTHESIS: 44 articles describing 27 study
      samples met inclusion criteria; 303 participants received growth hormone,
      representing 13.3 person-years of treatment. Participants were young (mean age,
      27 years [SD, 3]), lean (mean body mass index, 24 kg/m2 [SD, 2]), and physically
      fit (mean maximum oxygen uptake, 51 mL/kg of body weight per minute [SD, 8]).
      Growth hormone dosage (mean, 36 microg/kg per day [SD, 21]) and treatment
      duration (mean, 20 days [SD, 18] for studies giving growth hormone for >1 day)
      varied. Lean body mass increased in growth hormone recipients compared with
      participants who did not receive growth hormone (increase, 2.1 kg [95% CI, 1.3 to
      2.9 kg]), but strength and exercise capacity did not seem to improve. Lactate
      levels during exercise were statistically significantly higher in 2 of 3 studies
      that evaluated this outcome. Growth hormone-treated participants more frequently
      experienced soft tissue edema and fatigue than did those not treated with growth
      hormone. LIMITATIONS: Few studies evaluated athletic performance. Growth hormone
      protocols in the studies may not reflect real-world doses and regimens.
      CONCLUSION: Claims that growth hormone enhances physical performance are not
      supported by the scientific literature. Although the limited available evidence
      suggests that growth hormone increases lean body mass, it may not improve
      strength; in addition, it may worsen exercise capacity and increase adverse
      events. More research is needed to conclusively determine the effects of growth
      hormone on athletic performance.

PMID- 18347347
TI  - Summaries for patients. Universal surveillance for methicillin-resistant
      Staphylococcus aureus in 3 affiliated hospitals.

PMID- 18347348
TI  - Summaries for patients. Cognitive impairment without dementia in older adults.

PMID- 18347349
TI  - Universal surveillance for methicillin-resistant Staphylococcus aureus in 3
      affiliated hospitals.
AB  - BACKGROUND: The effect of large-scale expanded surveillance for methicillin
      resistant Staphylococcus aureus (MRSA) on health care-associated MRSA disease is
      not known. OBJECTIVE: To examine the effect of 2 expanded surveillance
      interventions on MRSA disease. DESIGN: Observational study comparing rates of
      MRSA clinical disease during and after hospital admission in 3 consecutive
      periods: baseline (12 months), MRSA surveillance for all admissions to the
      intensive care unit (ICU) (12 months), and universal MRSA surveillance for all
      hospital admissions (21 months). SETTING: A 3-hospital, 850-bed organization with
      approximately 40,000 annual admissions. INTERVENTION: Polymerase chain reaction
      based nasal surveillance for MRSA followed by topical decolonization therapy and
      contact isolation of patients who tested positive for MRSA. MEASUREMENTS: Poisson
      and segmented regression models were used to compare prevalence density of
      hospital-associated clinical MRSA disease (bloodstream, respiratory, urinary
      tract, and surgical site) in each period. Rates of bloodstream disease with
      methicillin-susceptible S. aureus were used as a control. RESULTS: The prevalence
      density of aggregate hospital-associated MRSA disease (all body sites) per 10,000
      patient-days at baseline, during ICU surveillance, and during universal
      surveillance was 8.9 (95% CI, 7.6 to 10.4), 7.4 (CI, 6.1 to 9.0; P = 0.15
      compared with baseline), and 3.9 (CI, 3.2 to 4.7; P < 0.001 compared with
      baseline and ICU surveillance), respectively. During universal surveillance, the
      prevalence density of MRSA infection at each body site had a statistically
      significant decrease compared with baseline. The methicillin-susceptible S.
      aureus bacteremia rate did not statistically significantly change during the 3
      periods. In a segmented regression model, the aggregate hospital-associated MRSA
      disease prevalence density changed by -36.2% (CI, -65.4% to 9.8%; P = 0.17) from
      baseline to ICU surveillance and by -69.6% (CI, -89.2% to -19.6%]; P = 0.03) from
      baseline to universal surveillance. During universal surveillance, the MRSA
      disease rate decreased during hospitalization and in the 30 days after discharge;
      no further reduction occurred thereafter. Surveillance with clinical cultures
      would have identified 17.8% of actual MRSA patient-days, and ICU-based
      surveillance with polymerase chain reaction would have identified 33.3%.
      LIMITATION: The findings rely on observational data. CONCLUSION: The introduction
      of universal admission surveillance for MRSA was associated with a large
      reduction in MRSA disease during admission and 30 days after discharge.

PMID- 18347350
TI  - Postpolypectomy colonoscopy surveillance guidelines: predictive accuracy for
      advanced adenoma at 4 years.
AB  - BACKGROUND: Lack of confidence in postpolypectomy surveillance guidelines may be
      a factor in the observed low adherence rates among providers. OBJECTIVE: To
      assess the 2006 postpolypectomy colonoscopy surveillance guidelines, which
      recommend 3-year follow-up colonoscopy for individuals with high-risk adenomas
      (defined as > or =3 adenomas or any advanced adenomas) and 5- to 10-year follow
      up for patients with 2 or fewer nonadvanced adenomas, who are considered to be at
      low risk. DESIGN: Analysis of prospective data from the Polyp Prevention Trial.
      SETTING: United States. PARTICIPANTS: 1905 patients who had colorectal adenomas
      removed at baseline screening or diagnostic colonoscopy and completed the trial.
      MEASUREMENTS: Baseline adenoma characteristics, risk-stratified according to
      definitions used in the guidelines, were examined as predictors for advanced
      adenoma recurrence. RESULTS: 125 patients (6.6%) had advanced and 629 (33.0%) had
      nonadvanced adenoma recurrence; 1151 (60.4%) had no recurrence within 4 years of
      follow-up. The probability of advanced adenoma recurrence was 0.09 (95% CI, 0.07
      to 0.11) among patients with high-risk adenomas at baseline and 0.05 (CI, 0.04 to
      0.06) among those with low-risk adenomas at baseline. The relative risk for
      advanced adenoma recurrence for patients with high-risk adenomas versus those
      with low-risk adenomas at baseline was 1.68 (CI, 1.19 to 2.38) when advanced
      adenoma recurrence was compared with no advanced adenoma recurrence and 1.76 (CI,
      1.26 to 2.46) when advanced adenoma recurrence was compared with no adenoma
      recurrence. The c-statistics for these 2 comparisons were 0.68 and 0.72,
      respectively. LIMITATION: Participants were self-selected and had restrictions on
      the degree of obesity. CONCLUSION: Although the risk for recurrence of advanced
      adenoma within 4 years is greater for patients with high-risk adenomas at
      baseline than for those with low-risk adenomas, the discrimination of this risk
      stratification scheme is relatively low.

PMID- 18347351
TI  - Prevalence of cognitive impairment without dementia in the United States.
AB  - BACKGROUND: Cognitive impairment without dementia is associated with increased
      risk for disability, increased health care costs, and progression to dementia.
      There are no population-based prevalence estimates of this condition in the
      United States. OBJECTIVE: To estimate the prevalence of cognitive impairment
      without dementia in the United States and determine longitudinal cognitive and
      mortality outcomes. DESIGN: Longitudinal study from July 2001 to March 2005.
      SETTING: In-home assessment for cognitive impairment. PARTICIPANTS: Participants
      in ADAMS (Aging, Demographics, and Memory Study) who were age 71 years or older
      drawn from the nationally representative HRS (Health and Retirement Study). Of
      1770 selected individuals, 856 completed initial assessment, and of 241 selected
      individuals, 180 completed 16- to 18-month follow-up assessment. MEASUREMENTS:
      Assessments, including neuropsychological testing, neurologic examination, and
      clinical and medical history, were used to assign a diagnosis of normal
      cognition, cognitive impairment without dementia, or dementia. National
      prevalence rates were estimated by using a population-weighted sample. RESULTS:
      In 2002, an estimated 5.4 million people (22.2%) in the United States age 71
      years or older had cognitive impairment without dementia. Prominent subtypes
      included prodromal Alzheimer disease (8.2%) and cerebrovascular disease (5.7%).
      Among participants who completed follow-up assessments, 11.7% with cognitive
      impairment without dementia progressed to dementia annually, whereas those with
      subtypes of prodromal Alzheimer disease and stroke progressed at annual rates of
      17% to 20%. The annual death rate was 8% among those with cognitive impairment
      without dementia and almost 15% among those with cognitive impairment due to
      medical conditions. LIMITATIONS: Only 56% of the nondeceased target sample
      completed the initial assessment. Population sampling weights were derived to
      adjust for at least some of the potential bias due to nonresponse and attrition.
      CONCLUSION: Cognitive impairment without dementia is more prevalent in the United
      States than dementia, and its subtypes vary in prevalence and outcomes.

PMID- 18347352
TI  - Expanding the universe of methicillin-resistant Staphylococcus aureus prevention.

PMID- 18347353
TI  - Guidelines for surveillance intervals after polypectomy: coping with the
      evidence.

PMID- 18347354
TI  - The Geriatrician's lab (yellow).

PMID- 18347355
TI  - Higher gonorrhea rates among African Americans than among White persons in the
      United States.

PMID- 18347356
TI  - Association between hospital mortality and residency work-hour regulations.

PMID- 18347357
TI  - Effect of work-hour regulations on outcomes.

PMID- 18347358
TI  - Hippocrates affirmed?

PMID- 18347359
TI  - D-dimer testing in pregnancy: clinically useful, but at what cost?

PMID- 18347360
TI  - Therapeutic hypothermia after cardiac arrest.

PMID- 18347361
TI  - Nonbenzodiazepine hypnotic use and cases of "sleep driving".

PMID- 18347362
TI  - Systemic effects of nitrofurazone-impregnated urinary catheters in trauma
      patients.

PMID- 18347363
TI  - Massachusetts health care reform is a pioneer effort, but complications remain.

PMID- 18347364
TI  - NSAIDs and cardiovascular disease.

PMID- 18347365
TI  - Risk prediction in pericarditis: who to keep in hospital?

PMID- 18347366
TI  - Ejection fraction: a measure of desperation?

PMID- 18347367
TI  - Arrhythmic substrate.

PMID- 18347369
TI  - Assessment of right ventricular function.

PMID- 18347370
TI  - Social inequalities and cardiovascular disease in South Asians.

PMID- 18347371
TI  - Medical treatment of Marfan syndrome: a time for change.
AB  - It is accepted practice to prescribe beta-blockers in order to retard aortic
      dilatation and prevent aortic dissection and rupture in patients with Marfan
      syndrome. A critical review of the published pharmacological studies shows this
      practice to be based on limited evidence. The data from small clinical and
      experimental studies with surrogate end points suggest greater potential benefit
      from alternative drug regimens, and a recent experimental study showed that
      losartan may interrupt the mechanism of disease as well as deal with its
      functional consequences. It is now essential to perform large, collaborative,
      randomised controlled trials with clinical end points of new treatments in Marfan
      syndrome.

PMID- 18347372
TI  - An interesting presentation of antiphospholipid syndrome.

PMID- 18347373
TI  - Telomere length is shorter in healthy offspring of subjects with coronary artery
      disease: support for the telomere hypothesis.
AB  - BACKGROUND: Telomeres are shorter in subjects with coronary artery disease (CAD)
      and may indicate premature biological ageing. However, whether shorter telomeres
      are a primary abnormality or secondary to the disease is unclear. OBJECTIVE: To
      investigate whether shorter telomeres are a primary abnormality or secondary to
      CAD, telomere lengths in healthy young adults with contrasting familial risk of
      CAD were compared. DESIGN: Case-control study. METHODS: Mean telomere restriction
      fragment (TRF) length in DNA from circulating leucocytes was determined by
      Southern blotting in 45 healthy offspring of subjects with premature CAD (case
      offspring) and 59 offspring from families without such a history (control
      offspring). Correlation in mean TRF length was also assessed in 67 offspring
      parent pairs. RESULTS: On average, a decrease of 27.5 (10.7) bp in mean TRF per
      year of age was found. The unadjusted mean TRF length was 6.34 kb (95% CI 6.13 to
      6.55) for case offspring and 6.75 kb (95% CI 6.57 to 6.94) for offspring of
      controls (p = 0.004). The adjusted difference in mean TRF between case and
      control offspring was 472 bp (95% CI 253 to 691, p<0.001), equivalent to about 17
      years of age-related attrition in telomere length. Furthermore, there was a
      significant positive correlation in mean TRF length between offspring and their
      parents (r = 0.37, p = 0.002). CONCLUSION: These findings suggest that
      inheritance of shorter telomeres is associated with increased familial risk of
      CAD. They support the hypothesis that telomere length is a primary abnormality
      involved in the pathogenesis of CAD.

PMID- 18347374
TI  - Left ventricular ejection fraction: are the revised cut-off points for defining
      systolic dysfunction sufficiently evidence based?

PMID- 18347375
TI  - Bubbles in the left cardiac cavities after diving.

PMID- 18347376
TI  - Acute renal artery embolism treated with a cardiac thrombectomy catheter.

PMID- 18347377
TI  - Prolonged QRS and QTc interval and mortality.

PMID- 18347379
TI  - Impact of blood pressure on the Doppler echocardiographic assessment of severity
      of aortic stenosis.

PMID- 18347381
TI  - The use of cardiac magnetic resonance imaging to determine the aetiology of left
      ventricular disease and cardiomyopathy.

PMID- 18347382
TI  - Management of the elderly patient with aortic stenosis.

PMID- 18347383
TI  - Anthracycline associated cardiotoxicity in survivors of childhood cancer.

PMID- 18347385
TI  - [Ion beam treatment: a new medical treatment system].
AB  - Ion beam treatment consists of a device and form of medical treatment. The device
      is a comprehensive system that consists of an irradiation system, a treatment
      planning system and a treatment verification system. The medical system consists
      of treatment criteria and a clinical path including daily treatment and care for
      patients. On April 1, 2001, HIBMC was opened as the world's first facility to
      provide both proton and carbon-ion radiotherapy. We have treated more than 1,300
      patients with a variety of malignant tumors including those of the skull base,
      head and neck, lung, liver and prostate. Excellent local control for these tumors
      has been obtained with minimum side effects. During the clinical trials and
      general practice, many tumors including radio-resistant tumors were treated with
      proton or carbon-ion. This autumn we will start the prospective randomized trial
      of two beams and we will analyze the difference between them. In future we would
      like to start new combination treatment with both beams.

PMID- 18347386
TI  - [National Cancer Act and Council for National Cancer Strategy].
AB  - Based on the National Cancer Act, the Council for National Cancer Strategy was
      inaugurated and compiled the Basic Plans for National Cancer Strategy. Japan's
      cancer control will be promoted in accordance with the said laws hereafter.
      Japan's cancer control marked its 1st year and entered a very important phase.
      The next several years will be extremely important periods for Japan.

PMID- 18347387
TI  - [Foster Plans for Cancer Specialists selected by MEXT in Japan].
AB  - Cancer, being the most common cause of death, develops in about 30% of Japanese
      people sometime during their lifetime. In order to confront this problem and
      improve Japan's standard of cancer treatment, it is essential to foster
      specialists in radiation therapy, chemotherapy and palliative management as well
      as oncology specialist nurses and pharmacists, fields in which our human
      resources are extremely limited. The Foster Plan for Cancer Specialists which
      medical schools in Japan play a key role in, receives the cooperation of other
      related universities and colleges, and was selected by the Ministry of Education,
      Culture, Sports, Science and Technology (MEXT) as an anti-cancer project in
      Japan. In 2007, 18 programs from the whole country have been selected. These
      plans call for specialists in the treatment of cancer to be educated mainly at
      the graduate school level, with extensive cooperation among the universities that
      have signed up for the systematic fostering plans, as well as the hospitals which
      are designated as partner facilities, in the prefectures in which the
      universities are located. This wide-range, professional development system is
      beyond the framework of the conventional graduate school education. It requires a
      system for university credit transfer, hospital-university collaboration, an
      internet schooling system, and the promotion in enrollment of working personnel.
      The regional framework is expected to include all universities, university
      hospitals, center hospitals for cancer treatment, local governments and
      professional training organizations in the prefectures for promoting its clinical
      tests and cancer registrations.

PMID- 18347388
TI  - [Cancer care in the new era: special emphasis on physician's mind-set anticipated
      in risk management].
AB  - In the more than 20 years, since the informed consent movement was begun, and 36
      years later than the US, at last the Japanese government enforced the Cancer
      Control Act in April of 2007. Japan has at last taken the right direction toward
      cancer control. Cancer is a systemic disease. The right diagnosis, standard
      treatment and expectation of risks, and prevention or therapy are crucial. Total
      management of patients with such a systemic progressing disease is very difficult
      without a system supervised by medical oncologist(s). Now outpatient chemotherapy
      is the major place of practice for medical oncology. Establishing an efficient
      outpatient chemotherapy system is key interest for hospital management and not
      only risk-management but also education and clinical research. Here the author
      makes several comments on these issues.

PMID- 18347389
TI  - [International standards of cancer treatment: looking back on patient activities
      that led to the Basic Act for Anti-Cancer Measures].
AB  - The Basic Act for Anti-Cancer Measures was enacted in June 2006. Behind this act
      were the activities of patients who protested the state of cancer treatment in
      Japan, in which patients were cut off without appropriate chemotherapy or
      palliative care after being told "there is nothing more we can do to treat you"
      These patients called for hospitals to carry out cancer treatment at world
      standards, requested early approval of drugs, demanded the training of
      specialists able to provide expert chemotherapy, and proposed ways for the
      provision of accurate cancer-related information. Their message won sympathy in
      society, and led to the current reforms in cancer treatment. Issues remain,
      however, such as the creation of a system for use of drugs outside their
      indication. A physician approach and medical system is also needed so that each
      patient can receive support with respect for his or her values when a cure cannot
      be expected.

PMID- 18347390
TI  - [Adjuvant chemotherapy with S-1 for head and neck carcinoma].
AB  - Combined chemotherapy is considered essential for further improvement of the cure
      rate of head and neck carcinoma. Chemotherapy in cases of head and neck carcinoma
      is administered with one of two objectives: as adjuvant therapy to increase the
      survival rate after radical treatment in the early stage of the disease, and to
      prolong the survival rate in cases with advanced or recurrent carcinoma. There
      is, however, no clear answer to the question of how these objectives can be
      accomplished. In our department, we use S-1 chemotherapy to achieve these goals.
      Our modified S-1 administration method until 2005 consists of a 3-week drug
      administration period followed by a 2-week drug-free period (3w-2w), or a 2-week
      administration period followed by a 2-week drug-free period (2w-2w). We
      determined the usefulness of the optimum administration method by examining the
      rate of completion of the treatment, and its safety and therapeutic efficacy. S-1
      administration was used in 68 cases of head and neck carcinoma until 2005. As a
      result, the rate of completion of the treatment and its safety were high. Further
      randomized controlled trials with a high degree of accuracy are needed to confirm
      whether or not our treatment method would improve the survival rate/ prolong the
      duration of survival in these patients.

PMID- 18347391
TI  - [Significance of pyrimidine nucleoside phosphorylase and dihydropyrimidine
      dehydrogenase levels to predict postoperative recurrence in primary breast
      cancer].
AB  - BACKGROUND: High expression of PyNPase (pyrimidine nucleoside phosphorylase) and
      DPD (dihydropyrimidine dehydrogenase) in breast cancer has been reported. Breast
      cancer patients with high expression of PyNPase reportedly have a poor prognosis.
      METHODS: We evaluated the relationship between postoperative prognosis, and
      clinicopathological factors including HER2 expression and the levels of PyNPase
      and DPD in breast cancer. PyNPase and DPD levels in tumors and nontumorous
      tissues were examined by enzyme-linked immunosorbent assay (ELISA). RESULTS:
      PyNPase and DPD levels in tumors were significantly higher than in non-tumorous
      tissues (p<0.001). The DPD levels in tumors associated with> or =2+expression of
      HER2 were significantly higher than in others (p=0.014). Disease-free survival in
      patients with<100 U/mg protein of PyNPase levels or<4 of PyNPase/DPD ratio was
      significantly better compared with others (p=0.022, p=0.014). CONCLUSION:
      PyNPase/DPD ratio may be a new prognostic marker in breast cancer.

PMID- 18347392
TI  - [omega-3 Fatty acid-containing diet (Racol) reduces toxicity of chemoradiation
      therapy for patients with esophageal cancer].
AB  - Recently, it is reported that a omega-3 fatty acid-containing diet (Racol)
      enhances innate immunity and reduces mucosal damage in the small intestine during
      chemotherapy. The aim of this study is to examine the effects of a omega-3 fatty
      acid-containing diet (Racol) on the toxicity of chemoradiation therapy (CRT) for
      patients with esophageal cancers. Toxicity of CRT was evaluated in 10 patients
      who took Rakol at a maximum dose of 600 mL/day during CRT, compared with 10
      patients who did not take Rakol. Regarding blood toxicity, the decrease of
      platelets did not differ between the former and the latter. However, the
      incidence of grade 2~4 neutropenia was lower in the former than in the latter
      (p=0.0043). With regard to gastrointestinal toxicity, the incidence of grade 2~4
      diarrhea was also lower in the former than in the latter (p=0.0118). Moreover,
      the incidence of grade 2~4 stomatitis/pharyngitis tended to decrease in patients
      who took Rakol compared with those who did not (p=0.0812). The current results
      indicated that a omega-3 fatty acid-containing diet (Racol) may be beneficial to
      patients with esophageal cancers who receive CRT by reducing CRT toxicity.

PMID- 18347393
TI  - [Present status and prospects for chemotherapy for advanced or recurrent gastric
      cancer in our hospital].
AB  - Since S-1 was approved in 1999, the response rate and the disease control rate of
      the chemotherapy for advanced or recurrent gastric cancer have improved. It is
      important to perform chemotherapy using key drugs and to plan the chemotherapy
      for each case. Of the 32 patients in our hospital, the median survival time (MST)
      was 21 months for chemotherapy in advanced or recurrent gastric cancer during
      2003-2006. MST for patients who had up to second- or third-line treatment was
      longer than for patients with up to first-line treatment. In addition, it there
      was no difference in prognosis for patients using CPT-11 or taxane at second-line
      after using S-1 at first-line treatment. The first-line chemotherapy for advanced
      or recurrent gastric cancer should be decided by the disease condition of each
      patient and the characteristics of each anti-cancer drug. In addition, the
      prognosis of patients will improve if second- or third-line chemotherapy can be
      performed.

PMID- 18347394
TI  - [Therapeutic experience of S-1 plus other drug combination therapy for synchronia
      multiple liver metastases of gastric cancer].
AB  - A treatment of multiple liver metastases of gastric cancer is very hard and its
      prognosis is extremely poor. At this time, we reviewed an efficacy of the
      therapeutic experience case with a new anticancer agent. The treatment was
      performed on nine cases of synchronia multiple liver metastases of gastric cancer
      since the new anticancer agent was introduced to the treatment. All of the 9
      gastric cancer cases were diagnosed as being resectable other than ones with
      metastases to the liver, or a primary tumor resection was performed on the cases.
      The 1st line chemotherapy regimen was a combination of S-1+CDDP intra-arterial
      injection. The 2nd line chemotherapy regimen was S-1+CPT-11 intra-arterial
      injection. Furthermore, the 3rd line chemotherapy regimen was an administration
      of paclitaxel. There were no adverse events, such as hematotoxicity and non
      hematotoxicity, that were greater than grade 3 during the duration of
      chemotherapy. Hence, we could continue the treatment regimen on all of the cases.
      The tumor responses for all of the cases were judged to be stable disease (SD).
      The best overall responses for all of the cases were judged to be progressive
      disease (PD). A median survival time (MST) of the treatment was 16 months, and
      that was significantly improved from 5.5 months, the regimen without a new
      anticancer agent (p=0.002). An ambulatory treatment was capable with the QOL in
      all of the cases. In conclusion, the tumor response did not show on the imaging,
      but it could be evaluable when there was an efficacy in the treatment that would
      support a daily life of patient.

PMID- 18347395
TI  - [Retrospective analysis of FOLFOX4 neurotoxicity for recovery from advanced
      colorectal cancer].
AB  - BACKGROUND: Oxaliplatin (L-OHP) in combination with infusional 5
      fluorouracil/leucovorin (FOLFOX), has been established as a key drug for advanced
      colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. No prior
      recovery from neurotoxicity data is available for Japanese patients treated by
      FOLFOX4 for advanced colorectal cancer. PURPOSE: We performed a retrospective
      study on the recovery from chronic neurotoxicity and period for discontinuing
      FOLFOX4 therapy due to neurotoxicity. PATIENTS AND METHOD: One hundred eighty
      seven patients with advanced or recurrent colorectal cancer were treated with
      FOLFOX4 regimen between April 2005 and March 2006. We evaluated chronic
      peripheral sensory neuropathy by National Cancer Institute Common Terminology
      Criteria for Adverse Events (version 3.0), and calculated the period of recovery
      from grade 3 and grade 2 neurotoxicity by the Kaplan-Meier method. RESULT:
      Seventy-two patients had to discontinue FOLFOX4 due to grade 3 and grade 2
      neurotoxicity. grade 2 and grade 3 neurotoxicity was observed in 39 (20.8%) and
      33 (17.6%) patients, respectively. Patients with grade 2 and grade 3
      neurotoxicity had a median age of 59 years (range, 35-75 years), and 62 years
      (range, 36-73 years), respectively. The median number of courses until expression
      of grade 2 neurotoxicity was ten (range, 2-23 courses) and that for grade 3
      neurotoxicity was also ten (range, 4-14 courses). The period of reducing grade 2
      neurotoxicity to grade 1 was 56 days, while that for reducing grade 3
      neurotoxicity to grade 1 was 106 days. FOLFOX4 was reintroduced in 15 patients
      with grade 2 neurotoxicity and in 14 patients with grade 3 neurotoxicity. The
      main reason that patients could not have reintroduction FOLFOX4 was early
      progression before reducing neurotoxicity to grade 1. The period from
      discontinuation of FOLFOX4 to disease progression was 88.5 days in partial
      response (PR) cases and 58 days in stable disease (SD) cases. PR cases took
      longer until disease progression than SD cases. CONCLUSIONS: The incidences of
      neurotoxicity were similar in Japanese patients compared with those reported in
      Western studies. These findings provide useful information for clinicians and
      patients using oxaliplatin.

PMID- 18347396
TI  - [Side effects of FEC100].
AB  - PURPOSE: The purpose was to investigate side effects of FEC100 treatment,
      particularly bone marrow suppression, nausea and vomiting. PATIENTS AND METHODS:
      We investigated side effects of FEC100 at the time of initial administration in
      49 breast cancer patients (including 3 with recurrence). We used a 5-HT3 receptor
      antagonist as an antiemetic agent, steroids and Haloperidol, an antidopamine
      agent. Antibiotics were also administered for five days from day 10. RESULTS: The
      mean nadir of white blood cell count was 1,492+/-575 microL, and the mean day on
      which the nadir was reached was the 13.0+/-1.45th day. Leukopenia of less than
      1,000 microL (grade 4) was seen in 8 (16.3%) of the 49 patients, and the
      incidence of leukopenia was particularly high (3/6, 50%) in patients with
      multiple bone metastases. Febrile neutropenia occurred in 4 (8.1%) of the 49
      patients, 2 of those 4 patients having multiple bone metastasis. Fifteen (30.6%)
      of the 49 patients had nausea, and 3 patients (6.1%) had vomiting. CONCLUSION:
      The results indicate that side effects of FEC100 treatment are tolerable.
      However, care is needed for patients with multiple bone metastases because of the
      strong bone marrow suppression in such patients.

PMID- 18347397
TI  - [An advanced metastatic breast cancer patient successfully treated with
      combination therapy including docetaxel, doxorubicin and cyclophosphamide (TAC)
      as salvage therapy].
AB  - We reported here a case of advanced breast cancer successfully treated with
      combination therapy including docetaxel, doxorubicin and cyclophosphamide (TAC)
      as salvage therapy. A 56-year-old male was referred to our hospital for treatment
      of recurrent metastatic breast cancer. When he was admitted, his general
      condition was poor due to massive intraperitoneal metastasis. We administered TAC
      chemotherapy (docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide
      500 mg/m(2), every 3 weeks). During chemotherapy, he showed no major adverse
      effects except grade 3 neutropenia, which could be easily managed with G-CSF
      administration. Metastatic lesions almost disappeared after 4 cycles of TAC. TAC
      therapy was considered to be acceptable as salvage therapy for a metastatic male
      breast cancer patient.

PMID- 18347398
TI  - [A case of triple negative recurrent breast cancer successfully treated with
      capecitabine+docetaxel combination chemotherapy].
AB  - A 73-year-old woman underwent pectoralis-preserving mastectomy for left breast
      cancer (papillotubular carcinoma, f, T2, ly0, v0, N1 (21/21), T2N1M0 (Stage IIB),
      ER (-), PgR (-), HER2 (-)) in August 2004. It was called a triple negative breast
      cancer. She received systemic chemotherapy using AC followed by paclitaxel. In
      February 2006 (disease- free interval of one year and five months), skin and
      chest wall recurrences in the left breast were revealed. Systemic chemotherapy
      using capecitabine (1,800 mg/body/day) monotherapy resulted in PD after 4
      courses. Subsequently, treatment with capecitabine+cyclophosphamide combination
      therapy resulted in PD after 6 courses. Since November 2006, treatment with
      capecitabine+docetaxel combination chemotherapy was initiated. Each course
      consisted of capecitabine at a dosage of 1,800 mg/body/day for 2 weeks and
      docetaxel at a dosage of 60 mg/body (day 8 only) followed by withdrawal for 1
      week. After 3 courses, a marked response was seen, and a total of 6 courses were
      performed. No serious side effect was revealed, and a marked response has been
      maintained. It is suspected that capecitabine+docetaxel combination therapy is
      useful for a triple negative recurrent breast cancer which is refractory to
      systemic chemotherapy.

PMID- 18347399
TI  - [A case of multidrug-resistant squamous cell lung carcinoma responding to S-1
      plus CPT-11 combination chemotherapy].
AB  - The patient was a 63-year-old man who consulted our hospital with complaints of a
      cough and breathing difficulties. His chest CT revealed a 25-mm mass in his right
      S1 hilar area with spiculation, disseminated nodule in right lung, and
      pericardial effusions. Also, bronchoscope and TBLB revealed squamous cell
      carcinoma. This patient was diagnosed as lung cancer (cT4N3M1, stage IV), and
      chemotherapy was initiated. The chemotherapy was given in the order of CBDCA
      (AUC3) +GEM (1,000 mg/m(2)), DOC (60 mg/m(2)), and VNR (25 mg/m(2)), and the
      tumor response was PD. S- 1 (120 mg/body/day, continuous administration for 2
      weeks followed by 1 week of rest) was chosen as fourth-line treatment, and a
      breast CT detected tumor size reduction following completion of the first course.
      However, after completion of three courses, the breast CT found tumor-enlargement
      again. Then the chemotherapy was changed to amrubicin (35 mg/m(2)), but the
      treatment was discontinued due to skin rash. We once experienced a size reduction
      with S-1, so S-1 (100 mg/body/day, day 1-14) plus CPT-11 (60 mg/m(2), day 1, 7,
      14) combination chemotherapy was conducted at 4-week intervals. After two courses
      were completed, tumor size reduction was observed by breast XP and CT. The
      response rate was 40.0%. Currently, seven courses were completed, and we will
      continue this treatment due to the tumor response of SD. The S-1 single treatment
      and S-1+CPT-11 combination chemotherapy showed efficacy for this difficult case
      of NSCLC with refractoriness to multiple cancer drug chemotherapy. This
      combination treatment should be investigated further for its therapeutic benefit.

PMID- 18347400
TI  - [Combination of carboplatin and gemcitabine is a safe and feasible regimen in
      adjuvant therapy for stage II and IIIA NSCLC].
AB  - BACKGROUND: Recently, several randomized trials have shown that postoperative
      adjuvant treatment improves survival among patients with completely resected non
      small cell lung cancer (NSCLC). Platinum-based chemotherapy has been reported to
      be effective for patients with postoperative stage II to IIIA. PATIENTS AND
      METHODS: In the present study, 5 patients with completely resected stage IIB and
      IIIA received carboplatin AUC 4 on day 1 and gemcitabine 1,000 mg/m(2) on days 1
      and 8 every 3 weeks for six cycles as adjuvant chemotherapy. RESULTS: No early or
      toxic deaths were observed. All patients were administered 6 cycles completely
      and safely. Three patients had grade 3 neutropenia and three had grade 2
      thrombocytopenia. One patient had grade 3 neutropenia on day 8 in the 2nd and 3rd
      cycle, and the medications were postponed for a week. Non-hematological toxicity
      including alopecia and neuropathy were not found. CONCLUSION: In the present
      study, the combination of carboplatin and gemcitabine has been a safe and
      feasible regimen in adjuvant therapy for stage II and IIIA NSCLC.

PMID- 18347401
TI  - [A patient with small cell lung cancer who developed a drug eruption due to
      concomitant therapy with carboplatin and etoposide].
AB  - We describe a case of a 69-year-old male patient with small cell lung cancer who
      developed a drug eruption due to concomitant therapy with carboplatin and
      etoposide. During simultaneous therapy with carboplatin and etoposide and
      radiotherapy, moderate drug eruption developed on the 11th day of the treatment.
      In a drug-induced lymphocyte stimulation assay, a negative result was confirmed
      for carboplatin, however, the responsiveness to etoposide could not be determined
      due to test drug-derived lymphocytic impairment. In the second course, irinotecan
      was administered instead of etoposide, and no drug eruption was observed. Thus,
      there was a high likelihood that the drug eruption observed in this case may have
      been caused by an allergic response to etoposide or its additives. Since some
      reports have demonstrated that the incidence of hypersensitivities, including
      drug eruption, to etoposide would increase in a dose-dependent manner, further
      accumulation and investigation of clinical data are required.

PMID- 18347402
TI  - [Two cases of severe myelosuppression from amrubicin in previously-treated small
      cell lung cancer].
AB  - The patients were a 59-year-old man and 68-year-old man with previously-treated
      small cell lung cancer (extensive disease). Amrubicin (40 mg/m(2) and 45 mg/m(2))
      was administered for 3 days after brain irradiation. Severe neutropenia continued
      for nine days from day 8 following administration. Although both patients had an
      infection, it improved by granulocyte-colony stimulating factor (G-CSF), and
      antibiotics, plus a blood transfusion. Particular attention for severe
      myelosuppression should be given to amrubicin therapy with previously-treated
      small cell lung cancer. However, a detailed blood test in course 1 and early
      administration of drugs such as G-CSF make this therapy feasible. In addition, to
      control the condition of patients, repeated administration of amrubicin with dose
      reduction is recommended.

PMID- 18347403
TI  - [Squamous cell carcinoma of the lower lip, completely responding to concurrent
      chemoradiotherapy with S-1].
AB  - Concurrent chemoradiotherapy (CCRT) can be used in order to increase both the
      local and systemic control of head and neck carcinoma. This report shows for the
      first time the assessment of CCRT with S-1 as a treatment modality for squamous
      cell carcinoma (SCC) of the lower lip. Surgical excision is usually the first
      choice for the treatment of SCC of the lower lip, followed by reconstruction.
      Such a treatment choice more or less compromises the cosmetic and/or functional
      status of the lip. We present our experience of utilizing CCRT with S-1 as a mode
      of treatment for SCC of the lower lip that yielded significant results while
      preserving the integrity of the lip.

PMID- 18347404
TI  - [A case of advanced gastric cancer responding to neoadjuvant S-1/CDDP therapy].
AB  - A 77-year-old male had complaints of epigastralgia. Gastrointestinal endoscopic
      examination revealed type 2 advanced gastric cancer. Computed tomography revealed
      metastatic Bulkey group 2 lymph nodes. The diagnosis was sStage IIIB gastric
      cancer (sT3 sN2sH0 sP0 CY0) at staging laparoscopy. S-1 (100 mg/body/day) was
      orally administered for 3 weeks followed by a drug-free 2 weeks, and CDDP (74
      mg/body/day) was given intravenously on day 8. After 3 courses of chemotherapy,
      the primary lesion and the regional lymph nodes were significantly reduced in
      size. He was judged as clinical PR, followed by total gastrectomy, splenectomy
      and lymph node dissection. The pathological findings showed that there were very
      few cancer cells in the primary lesion, and lymph nodes had become scarred and
      fibrous. The final diagnosis was T2N0 H0 P0, fStageIB and curability A.

PMID- 18347405
TI  - [A case of complete response treated by gastrectomy with lymphadenectomy and
      combined chemotherapy of peroral S-1 and CDDP by arterial infusion for gastric
      cancer with multiple liver metastasis].
AB  - A 70-year-old female was admitted to our hospital with high fever about 5 days
      before this writing, along with anemia and hyperglycemia. Upper gastrointestinal
      series and endoscopy revealed type 1 gastric cancer in the greater curvature. CT
      and MRI showed multiple liver metastasis in the right lobe. Distal partial
      gastrectomy with lymphadenectomy and cannulation of hepatic artery was performed.
      The pathological findings revealed moderately-differentiated adenocarcinoma, T2,
      N0, H1, M0, stage IV. The postoperative chemotherapy with S-1 (80 mg/day) was
      administered for 4 weeks followed by 1 week rest and CDDP (50 mg) administered
      once every 4 weeks by arterial infusion. Two months after operation the tumor
      marker values have become normal, and CT can hardly detect the metastatic liver
      tumors. At 8 months after operation, CT and MRI revealed complete disappearance
      of these tumors. Then, 12 months after operation, FDG-PET revealed no
      accumulation. Now, at 18 months, the CR stage has been maintained. Combined use
      of peroral S-1 and CDDP by arterial infusion is effective for multiple liver
      metastasis after gastrectomy in gastric cancer.

PMID- 18347406
TI  - [A successfully resected case of colorectal cancer with multiple liver metastases
      treated with FOLFIRI after failure of mFOLFOX6].
AB  - A sixty-year-old man was admitted with anorexia and abdominal mass. Colonoscopy
      revealed type 2 tumor at sigmoid colon. Computed tomography (CT) demonstrated
      multiple liver metastases. The patient was diagnosed as sigmoid colon cancer with
      multiple liver metastases. The patient was treated with mFOLFOX6 as neoadjuvant
      chemotherapy because the liver metastases were unresectable. However, after 2
      cycles of mFOLFOX6, the level of CEA and CA19-9 much increased. The regimen was
      replaced by FOLFIRI. The level of CEA and CA19-9 decreased after 2 cycles of
      FOLFIRI. CEA and CA19-9 further decreased and colonoscopy and CT revealed a
      partial response after 5 cycles of FOLFIRI. The patient was subjected to curative
      resection. Sigmoidectomy and liver resection were performed. Histological
      response was Grade 1b at liver metastasis. The patient was discharged and had an
      uneventful recovery. Six months after surgery, CEA and CA19-9 decreased to normal
      level, and the patient is free of recurrence. Neoadjuvant chemotherapy for
      metastatic colorectal cancer may render some unresectable patients resectable,
      affording these patients the possibility of prolonged survival. However, the
      optimal approach is unknown.

PMID- 18347407
TI  - [A long survival case of advanced colon cancer with lung metastasis and cancerous
      pleuritis responding to CPT-11 and S-1 combination therapy].
AB  - A 71-year-old man underwent right hemicolectomy for an ascending colon cancer
      (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil
      was performed, but CT scans and FDG-PET, conducted in May 2003, revealed
      cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy
      with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed.
      Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day;
      day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed
      a partial response. Only grade 2 vomiting was noted as an adverse reaction to the
      treatment, however, the patient has been managed on an outpatient basis for the
      last 3 years with good QOL and the cancer under control. This case suggests that
      this combination therapy can be expected to be highly effective as a safe
      approach for continuously maintaining the QOL of patients with advanced or
      recurrent colorectal cancer.

PMID- 18347408
TI  - [A case of advanced rectal cancer responding to radiation therapy and
      chemotherapy with S-1].
AB  - We report a case of a 72-year-old man with advanced rectal cancer who refused an
      operation for cancer therapy. We underwent radiation therapy (40 Gy) for the
      purpose of suppressing tumor bleeding. Consequently, we administered S-1 (100
      mg/day) orally. As a result, the tumor has disappeared by radiation therapy and
      chemotherapy with S-1 for 2 years. We have recognized no side effects. This
      therapy seemed to be an effective treatment for poor-risk elderly patients.

PMID- 18347409
TI  - [Concurrent chemoradiotherapy for squamous cell carcinoma of the anal canal
      report of four cases].
AB  - We have treated four Japanese patients with squamous cell carcinoma of the anal
      canal using concurrent chemoradiotherapy. The chemotherapy consisted of one or
      two cycles of mitomycin C 10 mg/m(2)/day (intravenous bolus injection) on day 1,
      and 5-fluorouracil 700 or 1,000 mg/m(2)/day (continuous intravenous infusion) on
      days 2-5 during radiotherapy. The total radiation dose was 40-54 Gy to the
      primary lesion. Acute grade 4 hematological toxicity was observed in one patient.
      These four patients have been alive and free of disease (follow-ups of 55, 14, 7
      and 5 months, respectively), with excellent function of the anal sphincter after
      treatment. These results suggest that concurrent chemoradiotherapy is safe and
      effective for Japanese patients with squamous cell carcinoma of the anal canal.

PMID- 18347410
TI  - [A case report of pseudomyxoma peritonei demonstrating complete response after
      intensive therapy consisting of cytoreductive surgery and adjuvant chemotherapy
      with paclitaxel and S-1].
AB  - A 74-year-old male with diffuse gelatinous ascites underwent cytoreductive
      surgery including ileocecal resection and greater omentectomy. Pathology revealed
      mucinous adenocarcinoma with low-grade malignancy originating in the appendix
      with disseminated peritoneal adenomucinosis, which was diagnostic of pseudomyxoma
      peritonei. A subcutaneous reservoir was implanted intraoperatively for
      intraperitoneal chemotherapy initiated at the time of operation. The patient
      received intraperitoneal chemotherapy with weekly paclitaxel at a dose of 60
      mg/m(2) for 3 weeks, followed by a 1-week rest, repeated every 4 weeks for 2
      months. Subsequently, paclitaxel was given intravenously at the same dose every 2
      weeks for 2 months, and then the patient was placed on oral S-1 at a dose of 100
      mg/body/day, administered daily for 2 consecutive weeks, followed by a 1-week
      rest, repeated every 3 weeks for 9 months. The patient tolerated the chemotherapy
      well, developing grade 1 anemia and grade 2 neutropenia plus elevation of total
      bilirubin. Tumor markers, CEA and CA19-9, fell to the normal range
      postoperatively, and have remained stable so far. A follow-up computed tomography
      (CT) scan revealed small ascites only in the right pelvis 8 months later after
      the initial operation, and complete disappearance of ascites 17 months later. Two
      years later, the patient presented with ileus, and required adhesionlysis as well
      as partial resection of adhesive ileum. No evidence of recurrent disease was
      confirmed intraoperatively as a second look. To date, the patient has been free
      of recurrence.

PMID- 18347411
TI  - [Marked effect of combination chemotherapy with tegafur-gimeracil-oteracil
      potassium and gemcitabine on a suspected case of pancreas cancer or gallbladder
      cancer metastasis to bone: further diagnosis of disseminated carcinomatosa of
      bone marrow recurrence after the 23 years of gastric cancer operation by autopsy
      findings].
AB  - A 70-year-old woman who underwent proximal gastrectomy for gastric cancer (poorly
      differentiated adenocarcinoma) of Stage IIIB at age 46 visited our hospital April
      2004 because of exacerbated pain by movement in the buttocks since November 2003.
      She showed multiple bone metastasis by CT (computerized tomography). Pancreas
      cancer or gallbladder cancer was suspected by CT, and a high tumor marker score
      (CA19-9 18,625 U/mL, DUPAN-II 15,000 U/ mL elevations were acknowledged).
      Although her symptoms were severe with performance status (PS) 4, she was
      administered combination chemotherapy with gemcitabine and cisplatin. After 2
      cycle therapy, her PS was improved to 2, but the tumor markers had elevated. So
      we changed the chemotherapy menu to S-1 and gemcitabine. Her tumor markers
      lowered and PS was improved to 1. There was a remarkable response to this
      chemotherapy, and the result of CT and bone scintigraphy suggested that her bone
      metastasis was improved. Because of hematologic relapse due to DIC at 1 year
      after the first treatment, she was readmitted to our hospital and later died. The
      autopsical result revealed recurrence of gastric cancer 23 years post
      operatively.

PMID- 18347412
TI  - [Plasma cell leukemia induced to complete remission with negative minimal
      residual disease by qualitative PCR analysis after hyper-CVAD and high-dose
      melphalan followed by autologous peripheral blood stem cell transplantation].
AB  - A 69-year-old Japanese man was diagnosed as having primary plasma cell leukemia.
      His malignant plasma cells had a chromosomal translocation t(11;14)(q13;q32) that
      created overexpression of cyclin D1. Two courses of VAD (vincristine,
      doxorubicin, dexamethasone) therapy failed to achieve complete remission. Three
      subsequent courses of hyper-CVAD (cyclophosphamide, vincristine, doxorubicin,
      dexamethasone) therapy successfully induced remission with negative FISH test for
      t(11;14)(q13;q32). Thereafter, the patient received high-dose melphalan (125
      mg/m(2)) followed by autologous peripheral blood stem cell transplantation.
      Cyclin D1 that was present prior to the high-dose chemotherapy, was no longer
      detected by qualitative PCR analysis. Despite complete cytogenetic remission, the
      disease relapsed 6 months later, and the patient eventually died 16 months
      following the diagnosis. Plasma cell leukemia is a rare hematological malignancy
      with a poor prognosis. The treatment has not been standardized yet. The present
      case suggested the effectiveness of the combination of hyper-CVAD and high-dose
      chemotherapy followed by autologous peripheral blood stem cell transplantation.
      Nevertheless, because of the short remission duration, intensification using
      tandem high-dose chemotherapy or maintenance using new agents such as bortezomib
      and thalidomide should be considered for improving the prognosis.

PMID- 18347413
TI  - [Trial of "Huber Plus" in outpatients with chemotherapy by blood port system].
AB  - We evaluated the advantages and disadvantages of Huber Plus through three
      outpatients treated with central venous (CV) port chemotherapy (FOLFOX). One of
      the three outpatients first received chemotherapy with safety huber (Huber Plus)
      in this study, and the huber needle was changed from non-safety to a safety huber
      (Huber Plus) in two of the three outpatients. All three outpatients were taught
      about needle removal methods and port care. In patients? education, 1) we used a
      skin model and training CV port, and 2) dressing materials were used as film
      dressing plus three-point fixation by Fixomull stretch. As a result, the safety
      system assured zero incidents. Moreover, the evaluation revealed that operability
      and pain of Huber Plus were not clinical problems. We suggest that Huber Plus is
      applicable in outpatient chemotherapy and that our care plan with patients?
      education might become a standard treatment.

PMID- 18347414
TI  - [Temozolomide: Temodal].
AB  - The oral alkylating agent, temozolomide (Temodal: TMZ), is the only anticancer
      drug that has been shown in a phase III study to improve survival in glioblastoma
      (GBM) when administered with concomitant radiotherapy. Pharmacokinetic studies
      have documented relatively high concentrations of TMZ in brain tumors and
      cerebrospinal fluid (20-40% of the area under the plasma concentration curve),
      and other studies have demonstrated that TMZ is effective for treatment of
      various brain tumors, including recurrent and newly diagnosed glioma, primary CNS
      lymphoma, metastatic melanoma, and neuroblastoma. Molecular markers that predict
      a favorable response to TMZ plus concomitant radiotherapy include methylguanine
      methyltransferase (MGMT) promoter methylation patients with GBM and chromosome
      1p/19q deletion in patients with anaplastic oligodendroglioma or low-grade
      glioma. Myelosuppression, nausea and constipation are relatively frequent in
      patients undergoing treatment with TMZ, and prophylaxis against Pneumocystis
      carinii pneumonia should be instituted. This article will summarize and discuss
      these issues as well as review ongoing and anticipated studies of TMZ in
      combination with other anti-cancer therapies.

PMID- 18347415
TI  - Salmonella typhimurium as a novel RNA interference vector for cancer gene
      therapy.

PMID- 18347416
TI  - Histamine in cancer: the dual faces of the coin.

PMID- 18347417
TI  - The effectiveness of retinoic acid treatment in bladder cancer: impact on
      recurrence, survival and TGFalpha and VEGF as end-point biomarkers.
AB  - INTRODUCTION AND AIMS: Being best-studied superficial bladder cancer (SBC)
      chemopreventives, retinoids' negative studies and toxicity were stumbling. With
      proper understanding of retinoid metabolism, we aimed at investigating combined
      ketoconazole (a strong inhibitor of retinoic acid-catabolizing cytochrome P450s)
      all-trans retinoic acid (Keto-atRA) SBC treatment. VEGF and TGFalpha levels are
      end-point pathogenetic biomarkers involved in early SBC. RESULTS: Keto-atRA
      treatment significantly improved survival time and decreased recurrence rate
      compared to control disease group, with tolerable and reversible side-effects.
      Treatment normalized induced levels of VEGF and TGFalpha with a positive
      correlation between these cytokines. MATERIAL AND METHODS: Seven days after TURT
      visible tumor(s), combined atRA 1 mg/kg for five days a week + Keto 200 mg twice
      daily for five days a week for three months were given to 16 patients with SBC
      stages Ta and T1 with various grades. Three months follow up/20 months used white
      light cystoscopy and urinary cytology. Recurrence rate and survival time were
      compared to a retrospective group of 25 patients of comparable age, stage and
      grade with TURT as sole treatment for SBC. VEGF and TGFalpha were measured in
      urine and serum of 12 normal subjects and treated patients. Samples were
      collected just before TURT, one week after TURT, at the end of one month and at
      the end of three months of treatment. CONCLUSIONS: The combination and schedule
      used for Keto-atRA therapy effectively reduced recurrence rate and increased
      survival time of SBC patients probably through reduction of VEGF and TGFalpha as
      major mitogenic/angiogenic factors; possibly by eliminating malignant cells that
      produce them.

PMID- 18347418
TI  - HIF-1alpha and STAT3 client proteins interacting with the cancer chaperone Hsp90:
      therapeutic considerations.
AB  - Heat shock protein 90 (Hsp90) is an ATP-dependent chaperone and a noteworthy
      component of cellular folding machinery in eukaryotes and bacteria. What makes
      Hsp90 specifically promising as a target for anti-cancer drugs is that many of
      its client proteins are involved in signaling and chromatin-remodeling pathways,
      and these pathways are often disrupted in many types of cancers. A very recent
      study by Lang et al. (Clin Cancer Res 2007; 13:6459-68) provide compelling
      evidence supporting a novel IL-6/STAT3/HIF-1alpha autocrine loop in pancreatic
      cancer cells, emphasizing the arresting role of Hsp90 inhibitors. Here, we
      discuss up-to-date advances towards the development of novel Hsp90 inhibitors
      designed to selectively block the growth and proliferation of tumor cells and
      proving to be intriguing targets for current clinical studies and cancer
      therapeutics.

PMID- 18347419
TI  - Targeting the human MUC1 oncoprotein: a tale of two proteins.

PMID- 18347420
TI  - Prevention of bladder cancer recurrence by retinoic acid-ketoconazole: a
      promising strategy?

PMID- 18347421
TI  - Biomarkers in breast cancer.

PMID- 18347422
TI  - Modulation in the activity of lactate dehydrogenase and level of c-Myc and c-Fos
      by modified base queuine in cancer.
AB  - Cancer is characterized by uncontrolled cell growth, which results from unlimited
      proliferation and disturbs various cellular activities. Queuine is a highly
      modified base analogue of guanine found at first anti-codon position of specific
      tRNAs i.e. tRNA(Tyr), tRNA(His), tRNA(Asp) and tRNA(Asn). These tRNAs are known
      as Q-family of tRNA. The tRNAs of Q-family are completely modified to Q-tRNAs in
      terminally differentiated somatic cells, however hypomodification of Q-tRNA is
      closely associated with cell proliferation and malignancy. Queuosine modification
      of tRNAs may be essential for normal development, differentiation and cellular
      functions. Physiological role of queuine remains ill defined but direct or
      indirect evidences suggest that queuine or Q-tRNA participates in many cellular
      functions such as regulation of cell proliferation, control of glycolytic
      metabolism, alteration in expression of proto-oncogenes, modulation of signal
      transduction pathways but the mechanism is not well known. Increase in LDH-A
      expression regulated by c-myc is well documented in a variety of tumor cells.
      Overexpression of proto-oncogenes cause deregulated cellular responses which may
      lead to development of cancer. The cellular proto-oncogenes like c-myc and c-fos
      have important role in cell growth, proliferation and differentiation. The
      present study is aimed to investigate queuine mediated modulation in the activity
      of lactate dehydrogenase and expression of proto-oncogenes like c-myc and c-fos
      in T-cell lymphoma (DLAT) induced cancerous mouse. The results indicate that
      elevated lactate dehydrogenase activity is brought down by queuine treatments and
      the elevated levels of c-Myc and c-Fos in DLAT cancerous mouse are down
      regulated, suggesting that queuine inhibits anaerobic metabolism and cell
      proliferation.

PMID- 18347423
TI  - Bismuth-213 radioimmunotherapy with C595 anti-MUC1 monoclonal antibody in an
      ovarian cancer ascites model.
AB  - PURPOSE: Control of ovarian cancer (OC) ascites remains a major objective in post
      surgical treatment. The aim of this study was to investigate the effect of
      targeted alpha therapy (TAT) for the control of ascites in an OC ascites mouse
      model; the biodistribution of (213)Bi-C595 and its long term toxicity. METHODS:
      The expression of tumor-associated antigen mucin-1 (MUC-1) in OVCAR3 ascites
      cells in mice and OC cancer tissues in patients was detected by indirect
      immmunostaining. The monoclonal antibody (MAb) C595 was labeled with (213)Bi
      using the chelator cDTPA to form the alpha-immunoconjugate (AIC). Mice were
      injected with different concentrations of AIC by i.p administration. Changes in
      tumor progression were assessed by measurement of the circumference of the
      abdomen. RESULTS: MUC-1 is strongly expressed in 73% of OC tissues. At 9 days
      post-cell inoculation in mice, a single injection of 355 MBq/kg of (213)Bi-C595
      can prolong survival by 25 days. A high tumor: blood ratio (5.8) was found in
      biodistribution study. The maximum tolerance dose (MTD) was more than 1180 MBq/kg
      up to 21 weeks. CONCLUSIONS: C595 is a specific targeting vector for ovarian
      cancer cells, which show a high percentage of expression of MUC1. (213)Bi-C595
      can effectively target and kill ovarian cancer cells in vitro and in vivo.
      (213)Bi-C595 is the recommended alpha conjugate for a Phase I clinical trial for
      ovarian cancer.

PMID- 18347424
TI  - hADA2a and hADA3: new players in beta-catenin signaling.

PMID- 18347425
TI  - Targeting Bcl-xL enhances the cytotoxicity of chemotherapeutics.

PMID- 18347426
TI  - Hypoxic regulation of miR-210: shrinking targets expand HIF-1's influence.

PMID- 18347427
TI  - Enhancing anti-cancer virotherapy with heat-shock protein-mediated immune
      response.

PMID- 18347428
TI  - RNA technology targeted to the WNT signaling pathway.

PMID- 18347429
TI  - Enhancement of p53 gene transfer efficiency in hepatic tumor mediated by
      transferrin receptor through trans-arterial delivery.
AB  - Transferrin-DNA complex mediated by transferrin receptor in combination with
      interventional trans-arterial injection into a target organ may be a duel-target
      oriented delivery means to achieve an efficient gene therapy. In this study,
      transferrin receptor expression in normal human hepatocyte and two hepatocellular
      carcinoma cells (Huh7/SK-Hep1) was determined. p53-LipofectAMINE with different
      amounts of transferrin was transfected into the cells and the gene transfection
      efficiency was evaluated. After VX2 rabbit hepatocarcinoma model was established,
      the transferrin-p53-LipofectAMINE complex was delivered into the hepatic artery
      via interventional techniques to analyze the therapeutic p53 gene transfer
      efficiency in vivo by Western blot, immunohistochemical/immunofluorescence
      staining analysis and survival time. The results were transferrin receptor
      expression in Huh7 and SK-Hep1 cells was higher than in normal hepatocyte.
      Transfection efficiency of p53 was increased in vitro in both Huh7 and SK-Hep1
      cells with increasing transferrin in a dose-dependent manner. As compared to
      intravenous administration, interventional injection of p53-gene complex into
      hepatic tumor mediated by transferrin-receptor, could enhance the gene transfer
      efficiency in vivo as evaluated by Western blot,
      immunohistochemical/immunofluorenscence staining analyses and improved animal
      survival (H = 12.567, p = 0.0019). These findings show the transferrin
      transferrin receptor system combined with interventional techniques enhanced p53
      gene transfer to hepatic tumor and the duel-target-oriented gene delivery may be
      an effective approach for gene therapy.

PMID- 18347430
TI  - Learning about ovarian tumorigenesis by watching Cables.

PMID- 18347431
TI  - Tumor growth signaling inhibition: targeting multiple pathways.

PMID- 18347432
TI  - Mesenchymal stem cells in cancer: friends or foes.

PMID- 18347433
TI  - Is Alba an RNase P subunit?
AB  - It has been suggested that Alba, a well-established chromatin protein in Archaea,
      is also a subunit of the archaeal RNase P holoenzyme, based on the observation
      that the homolog of this protein in humans has been shown to be associated with
      RNase P activity. Using the same biochemical methods we used previously to show
      that four other proteins homologous to eukaryotic RNase P proteins are bona fide
      RNase P subunits in Archaea, we could not detect any association of the Alba
      homolog in Methanothermobacter thermoautotrophicus (Mth1483p) with the RNase P
      holoenzyme. In addition, the presence of Mth1483p did not enhance the activity of
      RNase P holoenzyme reconstituted from recombinant subunits. In conclusion, we
      find no evidence that Alba is an RNase P subunit.

PMID- 18347434
TI  - Small RNAs and their big implications: in vivo, in vitro, in silico.

PMID- 18347435
TI  - Epstein-Barr virus-encoded latent membrane protein 1 (LMP1) induces the
      expression of the cellular microRNA miR-146a.
AB  - MicroRNAs (miRNAs) are involved in sequence-specific cleavage, translational
      repression or deadenylation of specific target mRNAs resulting in post
      transcriptional gene silencing. Epstein-Barr Virus (EBV) infection induces
      cellular non-coding (nc)RNAs e.g., the "vault" RNAs or miRNAs such as miR-21, miR
      155 or miR-146a. MiR-146a is upregulated in various tumours and plays a role in
      innate immunity. We show that the EBV-encoded latent membrane protein 1 (LMP1)
      induces the expression of miR-146a via NFkappaB. LMP1 activates the miR-146a
      promoter but not a promoter with a mutation of the NFkappaB-response elements.
      Conversely, a LMP1-mutant deficient in NFkappaB-activation failed to activate the
      promoter. The "CAO"-LMP1 variant which has an increased potential to induce
      NFkappaB also showed a higher ability to activate the miR-146a promoter as
      compared to standard B95.8-LMP1. Northern blotting revealed high levels of miR
      146a and miR-155 in the Burkitt's lymphoma cell line Jijoye which expresses LMP1
      while the LMP1-deficient P3HR1 mutant derived from Jijoye expresses less miR-146a
      or miR-155. Likewise, EBV-latency type I Burkitt's lymphoma cells with low LMP1
      levels also contain low levels of either miR-146a or miR-155 while their levels
      are increased in LMP1-expressing EBV-latency type III BL cells. Expression of
      LMP1 in P3HR1 cells upregulates miR-146a levels. Neither miR-146a nor miR-155 are
      detectable in BCBL-1 cells transformed by the Kaposi-Sarcoma Herpes virus
      (KSHV/HHV8). It is possible that the induction of miR-146a plays a role in the
      induction or maintenance of EBV latency by modulating innate immune responses to
      the virus infected host cell.

PMID- 18347436
TI  - A minimal WLE2 element is not sufficient to direct apical localization in the
      absence of RNAs containing the full length wingless 3'UTR.
AB  - The mRNAs encoded by the Drosophila Wnt-1 homologue, wingless, are localized to a
      small region of the apical cytoplasm in early embryonic epithelial cells. This
      requires the activity of cis-acting sequences within the 3' untranslated region
      called wingless localization elements (WLEs). One of these, WLE2, was identified
      initially as a cis-acting sequence that directed apical localization of in vivo
      expressed mRNAs in four to five hour Drosophila embryos. To determine the precise
      activity of WLE2 during wingless apical localization, we performed an in-depth
      mutagenesis of this sequence. Using both direct-injection and in vivo transgenes
      we determined that WLE2, by itself, is not sufficient to direct binding of trans
      acting factors that mediate apical RNA transport in embryonic cells. Rather, RNAs
      containing only WLE2 are transported apically only in the presence of a second
      RNA containing other cis-acting localization sequences of the wingless 3'
      untranslated region. This co-requirement for WLE2 and additional wingless 3'UTR
      sequences is likely a required function during apical localization, as mutations
      within WLE2 can modify the apical localization activity of RNA molecules that
      contain other wingless localization signals. This suggests that, similar to other
      localized mRNAs like bicoid, wingless localization may require specific RNA-RNA
      interactions as well as recognition by cytoplasmic RNA localization complexes.

PMID- 18347437
TI  - RNA chaperones, RNA annealers and RNA helicases.
AB  - RNA molecules face difficulties when folding into their native structures. In the
      cell, proteins can assist RNAs in reaching their functionally active states by
      binding and stabilizing a specific structure or, in a quite opposite way, by
      interacting in a non-specific manner. These proteins can either facilitate RNA
      RNA interactions in a reaction termed RNA annealing, or they can resolve non
      functional inhibitory structures. The latter is defined as "RNA chaperone
      activity" and is the main topic of this review. Here we define RNA chaperone
      activity in a stringent way and we review those proteins for which RNA chaperone
      activity has been clearly demonstrated. These proteins belong to quite diverse
      families such as hnRNPs, histone-like proteins, ribosomal proteins, cold shock
      domain proteins and viral nucleocapsid proteins. DExD/H-box containing RNA
      helicases are discussed as a special family of enzymes that restructure RNA or
      RNPs in an ATP-dependent manner. We further address the different mechanisms RNA
      chaperones might use to promote folding including the recently proposed theory of
      protein disorder as a key element in triggering RNA-protein interactions.
      Finally, we present a new website for proteins with RNA chaperone activity which
      compiles all the information on these proteins with the perspective to promote
      the understanding of their activity.

PMID- 18347438
TI  - Identification of the RNA binding regions of SRP68/72 and SRP72 by systematic
      mutagenesis of human SRP RNA.
AB  - Within the large domain of the human signal recognition particle (SRP), 18 mutant
      SRP RNAs were constructed to disrupt Watson-Crick and G-U basepairs in helices 5,
      6 and 8. Using a double-filter assay, the competitive binding of the mutant RNAs
      to purified human SRP68/72 or to a 7.4 kDa RNA-binding fragment of SRP72 (72frg)
      was measured. Binding of SRP68/72 was impaired by several mutations in the large
      domain with the most pronounced effects caused by changes in helix 5 (residues
      222-231) and helix 8 (residues 176-191 and 202-214). Binding of the 72frg was
      diminished prominently by altering helix 5, in particular residues 120-128, and
      was unaffected by deleting helices 6 and 8. Deleting helix 8 diminished binding
      of SRP68/72 to a greater extent than deleting helix 6. The data suggest that
      nucleotide residues throughout most of the large SRP domain are directly and/or
      indirectly engaged in the binding of SRP68. In contrast, SRP72 binds only to a
      portion of the 5ef region.

PMID- 18347439
TI  - Heart rate variability in white-coat hypertension.
AB  - OBJECTIVES: The objective of this study was to compare heart rate variability
      (HRV) in patients with essential hypertension, in patients with white-coat
      hypertension and in normotensive control individuals, and to investigate a
      possible relation between HRV and vasoactive hormones. METHODS: Patients with
      essential hypertension (n=19, 61 years, median and interquartile range: 40-66
      years), patients with white-coat hypertension (n=8, 52 years, median and
      interquartile range: 41-64 years) and normotensive participants (n=13, 50 years,
      median and interquartile range: 39-57 years) participated in the study. HRV was
      measured at rest in the supine position, during standing and during controlled
      forced breathing (respiration frequency >20/min). Power spectral density was
      calculated using Fourier transformation. RESULTS: Controlled breathing caused a
      decrease in low frequency (LF) variation and LF/high frequency variation (LF/HF)
      in all blood pressure groups. The decrease in LF was smaller in the hypertensive
      group (-60 ms2) than in the normotensive group (-139 ms2) (P=0.03; hypertensive
      group vs. normotensive group). The decrease in LF/HF induced by controlled
      breathing was -0.9 ms in the hypertensive group, -2.0 ms2 in the white-coat
      hypertensive group and -2.8 ms2 in the normotensive group, (P=0.037; hypertensive
      group vs. normotensive group). We found a positive correlation between baseline
      plasma renin concentration and LF (r=0.330, P=0.037) and LF/HF (r=0.378, P=0.016)
      at rest. CONCLUSION: The observed differences in HRV might reflect the impaired
      responsiveness to autonomic challenge in hypertensive patients. We did not find
      the HRV spectrum in white-coat hypertension different from the HRV spectrum in
      hypertension or normotension.

PMID- 18347440
TI  - Dialysis-induced hypotension is associated with impaired aortic elasticity in
      patients undergoing chronic hemodialysis.
AB  - BACKGROUND: The pathogenesis of dialysis-induced hypotension (DIH) is
      multifactorial and may include increased aortic stiffness. This study was
      undertaken to determine aortic elastic properties in patients undergoing
      hemodialysis with and without DIH, and to assess the effects of DIH on mortality.
      METHODS: Aortic stiffness and left ventricular functions were evaluated in 70
      patients undergoing hemodialysis with (n=34) and without DIH (n=36). We also
      evaluated total mortality at 36 months. RESULTS: Patients with DIH in comparison
      with patients without DIH, had lower aortic strain (5.0+/-3.8 vs. 7.8+/-3.0%,
      P<0.005) and distensibility (2.3+/-1.9 vs. 3.2+/-1.7 cm2/dyn/10(3), P<0.01). In
      univariate analysis, age, aortic stiffness and left ventricular systolic
      dysfunction, and coronary artery disease were also found to be the main factors
      associated with DIH. On multivariate logistic regression analysis, aortic
      distensibility [odds ratio (OR): 0.61; 95% confidence interval (95% CI): 0.40
      0.93; P=0.01] and the coronary artery disease (OR: 6.46; 95% CI: 1.62-25.73;
      P=0.009) remained as significant variables associated with DIH. During follow-up
      period, 12 out of 34 patients with DIH died compared with 4 out of 36 patients
      without DIH (log rank, P=0.02). CONCLUSION: Our data suggest that DIH is strongly
      associated with increased aortic stiffness and poor outcome. Larger long-term
      follow-up studies, however, investigating whether the DIH plays a surrogate or
      causative role on mortality in patients undergoing hemodialysis should be
      designed.

PMID- 18347441
TI  - Assessment of left ventricular systolic and diastolic function by tissue Doppler
      analysis in patients with hypertension with or without hyperuricemia.
AB  - OBJECTIVE: Hyperuricemia (HU) is a well-recognized risk factor for cardiovascular
      diseases. The independence of this association from other confounding factors has
      remained controversial. The possible contributory effect of HU to myocardial
      impairment produced by hypertension (HT), however, has not been clarified yet.
      The study was designed to assess the left ventricular (LV) systolic and diastolic
      function in patients with HT with or without HU. Tissue Doppler imaging (TDI) was
      used for detailed analysis as this method was superior to other conventional
      echocardiographic techniques. METHODS: The study participants consisted of 27
      patients (men 56%, mean age+/-SD; 55+/-10 years) with HT without HU, and 27
      patients with HT with HU (men 62%, mean age+/-SD; 56+/-9 years), and 27 age
      matched healthy control participants (men 57%, mean age+/-SD; 53+/-11 years).
      Cardiac functions were determined using echocardiography, comprising standard two
      dimensional and conventional Doppler and TDI. Peak systolic myocardial velocity
      at mitral annulus (Sm), mitral inflow velocities and early diastolic mitral
      annular velocity (Em), late diastolic mitral annular velocity (Am), peak systolic
      mitral annular velocity, Em/Am, and myocardial performance index were calculated
      by TDI. RESULTS: Mitral inflow velocities and tissue Doppler-derived mitral
      annular diastolic velocities were significantly different in the patient groups
      (HT without HU and HT with HU) compared with the control cases. Tissue Doppler
      derived myocardial performance index (LV-MPI) was significantly impaired in the
      patient groups compared with those of the control's (0.48+/-0.09, 0.53+/-0.07,
      and 0.39+/-0.07, respectively, P<0.001). Significant differences were also
      observed between the patients who had HT without HU and the patients who had HT
      with HU regarding LV-MPI. Significant correlations were observed between the
      serum uric acid levels and LV function parameters.

PMID- 18347442
TI  - No further decrease in blood pressure when the interval between readings exceeds
      one hour.
AB  - OBJECTIVE: The assessment of blood pressure (BP) in individuals is traditionally
      based on a few BP readings obtained at intervals of just a few minutes. We
      examined if increasing intervals between BP readings on one visit would have an
      impact on the BP estimates. METHODS: We conducted an examination survey of
      cardiovascular risk factors in the general population aged 25-64 years in
      Seychelles (Indian Ocean), attended by 1255 of 1565 eligible participants. BP was
      measured once shortly after participants' arrival to the study centers (BP1) and
      twice before discharge, 15-351 min later (BP2, BP3; separated by 2 min). RESULTS:
      Mean (standard error) BP1 was 135.1 (0.7)/87.9 (0.4) mmHg, BP2: 130.7 (0.6)/85.1
      (0.4) mmHg and BP3: 128.4 (0.6)/83.9 (0.3) mmHg. The difference in BP between the
      first and the last measurements (DeltaBP1-BP3) was, respectively, 5.8 (1.3)/2.6
      (0.9) mmHg for a time interval between BP1 and BP3 of 15-60 min, 6.3 (0.5)/3.9
      (0.3) mmHg for 61-120 min, 6.9 (0.6)/4.1 (0.4) mmHg for 121-240 min and 7.4
      (0.7)/4.3 (0.5) mmHg for 241-351 min (P-trend for systolic/diastolic BP:
      0.15/0.49). In multivariate analysis, both systolic and diastolic DeltaBP were
      associated with the initial BP level and the female sex but not with time (in
      minutes) between BP readings (for systolic/diastolic BP, P=0.12/0.34).
      CONCLUSION: The decrease in subsequent BP readings obtained did not differ
      whether the time interval between BP measurements was larger or smaller than 1 h.
      This indirectly suggests that extending the time interval between repeated BP
      readings on one single visit is unlikely to be a valid, alternative strategy to
      the recommendation of gathering BP readings on several, separate visits to define
      hypertension.

PMID- 18347443
TI  - Lax sphygmomanometer standard causes overdetection and underdetection of
      hypertension: a computer simulation study.
AB  - OBJECTIVE: To quantify overdetection and underdetection of hypertension caused by
      systematic sphygmomanometer errors permitted by the current European standard (EN
      1060 'noninvasive sphygmomanometers'). METHODS: We carried out Monte Carlo
      simulation of measurement of blood pressure (BP) of the adult Australian
      population using sphygmomanometers showing systematic errors compliant with the
      EN 1060 standard. We repeated the simulations limiting systematic
      sphygmomanometer errors to +/-1 mmHg. Simulated BP measurements included
      systematic sphygmomanometer error, random intraindividual BP variability and
      random measurement error. RESULTS: After three visits, underdetection of
      hypertension is common owing to variability of BP measurements and systematic
      errors of sphygmomanometers. After three visits, the wide tolerances of EN 1060
      are responsible for approximately 4.9 and 11% of underdetection of systolic and
      diastolic hypertension, respectively. Underdetection is worse in some groups, for
      example, permitted sphygmomanometer error causes 20% of all undetected systolic
      hypertension in 18-24 year-old women. The current standard also results in
      overdetection of hypertension. Permitted sphygmomanometer error causes 5.8 and
      14% of the overdetection of systolic and diastolic hypertension, respectively,
      after three visits. Overdetection is worse in some groups, for example, after
      three visits, permitted sphygmomanometer error causes 19% of falsely detected
      diastolic hypertension in 18-24 year-old men. For all adults, reduction of
      permitted sphygmomanometer error to +/-1 mmHg achieves approximately the same
      improvement in hypertension detection as at least one additional visit to the
      clinician. CONCLUSION: Systematic sphygmomanometer errors permitted by the
      current standard are a preventable cause of clinically significant overdetection
      and underdetection of hypertension. The standard should be revised to make the
      effects of equipment related systematic errors negligible compared with the
      effects of physiological variability.

PMID- 18347444
TI  - Self-measurement of blood pressure: validation of the Braun BP VitalScan Plus
      1650 monitor according to the European Society of Hypertension International
      Protocol.
AB  - BACKGROUND: Self-measurement of blood pressure (BP) has been increasingly
      encouraged as a supplement to measurements in the clinic. OBJECTIVE: The main
      objective of this study is to clinically evaluate a new device for self
      measurement of BP according to the International Protocol of the European Society
      of Hypertension (2002). METHODS: Measurements of systolic and diastolic BP in 33
      volunteers (15 for phase 1 and a further 18 for phase 2 providing 99
      measurements) were obtained using the mercury sphygmomanometer (HgS;
      Baumanometer) and the Braun BP VitalScan Plus 1650 device. Nine sequential same
      arm measurements between the test device and the standard HgS were carried out
      according to the International Protocol of the European Society of Hypertension
      in two phases (phase 1, phase 2.1 and phase 2.2). RESULTS: The device passed
      phase 1 as 30 systolic and 33 diastolic readings fell within 5 mmHg exceeding the
      25 required. In addition, the equipment also passed phase 2.1 as 74 systolic and
      77 diastolic readings fell within 5 mmHg exceeding the 65 required for being
      approved. Finally, it also passed the phase 2.2 as 25 volunteers for systolic and
      28 for diastolic had at least 2/3 of their comparisons falling within 5 mmHg
      (exceeding the 22 required) and only two of the 33 volunteers had their three
      comparisons over 5 mmHg apart (at the most three are required). The difference
      against-mean plots showed that the disagreement between the HgS and the device
      was -2.57+/-4.36 mmHg for systolic BP and +0.83+/-4.97 mmHg for diastolic BP,
      respectively. CONCLUSION: The equipment passed the different phases
      satisfactorily and the study suggests that it can be used for self-BP monitoring.
      The device, however, needs to be used with care by the patients following the
      instructions, because even when it may be accurate in a laboratory setting, there
      is potential for them to be used inaccurately in the home setting.

PMID- 18347445
TI  - Accuracy evaluation of the 'Cardiette BP one' ambulatory blood pressure monitor.
AB  - OBJECTIVE: Blood pressure (BP) 'Cardiette BP one' system (BP one) is an
      oscillometric ambulatory BP monitor manufactured in Italy in conformity to
      current regulations for medical devices. We decided to determine the accuracy of
      measures made with BP one, using the protocol of the British Hypertension Society
      published in 1990, and revised in 1993, for evaluating the accuracy of BP
      measurement devices. METHODS: The evaluation included before-use calibration, in
      use assessment, after-use calibration, and static device validation that involved
      85 participants. RESULTS: The mean difference between manual readings with
      sphygmomanometer and automatic ones with the device were -0.36+/-5.74 (mean+/-SD)
      for systolic values and 2.52+/-4.87 for diastolic values. On the basis of the
      percentages of measurements differing from the mercury sphygmomanometer standard
      by <or=5, <or=10, and <or=15 mmHg, the device was graded 'A' for systolic and
      diastolic BP, for low, median, and high BP values. CONCLUSION: On the basis of
      the standards indicated by the 1993 modified British Hypertension Society
      protocol, the BP one recorder can be classified as 'A' grade both for systolic
      and diastolic pressure.

PMID- 18347446
TI  - Accuracy assessment of the Tensoval duo control according to the British and
      European Hypertension Societies' standards.
AB  - OBJECTIVE: Noninvasive blood pressure (BP) measurement is dependent on either
      auscultation or oscillometry. The Tensoval duo control device uses auscultatory
      and/or oscillometric technology to determine BP. We evaluated the accuracy of
      this device in adults according to the British Hypertension Society (BHS)
      protocol and the International Protocol of the European Hypertension Society.
      METHODS: Ethical approval was obtained and participants gave written informed
      consent. Eighty-five participants who fulfilled the protocol criteria were
      recruited. Nine sequential same arm measurements were taken from each participant
      by two trained observers, comparing the device to mercury sphygmomanometery. Data
      analysis was performed according to the respective protocol guidelines. RESULTS:
      The device achieved an A grade for both systolic and diastolic pressures with 68,
      91 and 98% of systolic and 73, 91 and 98% of diastolic differences within the
      <or=5, <or=10 and <or=15 mmHg categories of the BHS protocol. It maintained an
      A/A grade throughout the low, medium and high-pressure analysis. It also achieved
      the requirements of the Association for the Advancement of Medical
      Instrumentation (ANSI/AAMI SP10 protocol) with a mean difference (SD) of -2.4
      (6.0) mmHg for systolic and 0.9 (6.3) mmHg for diastolic pressure. It also passed
      all the phases of the International Protocol. CONCLUSION: The Tensoval duo
      control can be recommended for clinical and home care use in an adult population
      according to the criteria of the BHS protocol and the International Protocol. It
      is the first fully automated BP device for self-measurement to maintain an A/A
      grade throughout the low, medium and high-pressure ranges.

PMID- 18347447
TI  - Validation of the Omron M6 (HEM-7001-E) upper arm blood pressure measuring device
      according to the International Protocol in elderly patients.
AB  - OBJECTIVE: Despite the widespread use of automated self-measurement monitors,
      there is limited published evidence on their accuracy and reliability on
      different patient groups. The objective of this study was to evaluate the
      accuracy and reliability of the Omron M6 (HEM-7001-E) upper-arm blood pressure
      (BP) device against mercury sphygmomanometer on elderly patients according to the
      criteria of the International Protocol. DESIGNS AND METHODS: Thirty-three
      patients above 65 years of age, who were classified based on the BP categories of
      the International Protocol, were recruited for the study. BP measurements at the
      upper arm with the Omron M6 were compared with the results obtained by two
      trained observers using a mercury sphygmomanometer. Nine sequential BP
      measurements were taken. During the validation study, 99 measurements were
      obtained from 33 patients for comparison. The first phase was carried out on 15
      patients and if the device passed this phase, 18 more patients were selected.
      RESULTS: Mean discrepancies and standard deviations of the device
      sphygmomanometer were 1.4+/-5.3 mmHg for systolic BP (SBP) and -1.4+/-4.5 mmHg
      for diastolic BP (DBP) in the study group. The device passed phase 1 in 15
      patients. In phase 2.1, from the total 99 comparisons, 76, 92, and 97 for SBP and
      77, 94, and 99 for DBP were less than 5, 10, and 15 mmHg, respectively. The Omron
      M6 passed phases 2.1 and 2.2 in the elderly group of patients. CONCLUSION: The
      Omron M6 (HEM-7001-E) upper-arm BP monitor passed according to the International
      Protocol criteria and can be recommended for use in elderly patients.

PMID- 18347448
TI  - Improving blood pressure control and clinical outcomes through initial use of
      combination therapy in stage 2 hypertension.
AB  - Poor control of clinic and 24-h blood pressure (BP) is associated with enhanced
      risk of all cardiovascular disease events. Certain patient groups including the
      elderly, African-Americans, and those with hypertension and comorbid disease are
      difficult to control, as are patients with stage 2 hypertension (systolic
      BP>or=160 mmHg or diastolic BP>or=100 mmHg). It has been estimated that more than
      two-thirds of high-risk hypertensive patients with stage 2 hypertension and all
      hypertensive patients with diabetes mellitus or kidney disease will require two
      or more antihypertensive agents from different therapeutic classes to reach BP
      goals. Combining agents with distinct and complementary modes of action can
      address different pathophysiologic mechanisms involved in hypertension and may
      lead to more complete and prompt reductions in BP. Tolerability may also improve,
      as certain classes of antihypertensive agents ameliorate adverse effects
      associated with other agents. Patients may benefit from fixed-dose combinations
      of drugs as this simplifies the regimen and may improve adherence with therapy,
      control of BP, and ultimately lead to reductions in cardiovascular events. Recent
      data and treatment guidelines support the use of a combination strategy as
      'initial' antihypertensive therapy in high-risk patients with stage 2
      hypertension.

PMID- 18347449
TI  - A physician with pounding headaches.

PMID- 18347450
TI  - The crisis in scholarly publishing: open access to the rescue?

PMID- 18347451
TI  - Frequency of anti-retinal antibodies in normal human serum.
AB  - BACKGROUND: Anti-retinal antibodies have been described in the context of
      autoimmune retinopathies and are often presumed to be pathogenic or disease
      associated. However, full characterization of patterns of anti-retinal antibody
      reactivity in normal human serum has been limited. The purpose of this work was
      to identify the profile of anti-retinal IgG antibodies in serum used as controls
      in laboratory testing. METHODS: Normal human sera used in commercial diagnostic
      laboratories were tested for the presence of immunoreactivity against soluble
      human retinal proteins using Western blot analysis of fractionated soluble human
      retinal proteins. Reactivity was quantified using computerized densitometry, and
      the level of reactivity was standardized relative to a control positive serum
      with known reactivity against recoverin. RESULTS: Some anti-retinal reactivity
      was observed in the majority of all tested normal sera. Reactivity against one to
      two protein bands was observed in 33%. Reactivity against five or more distinct
      bands was observed in 22%. There was a tendency for serum from women to react
      with three or more protein bands compared with serum from men. CONCLUSIONS: The
      presence of anti-retinal antibodies is observed in a majority of normal control
      human sera, suggesting that identification of new candidate retinal autoantigens
      should be cautiously interpreted and subject to rigorous testing for disease
      association. Additional studies will aid development of a standardized protocol
      for validation of potential pathogenic seroreactivity.

PMID- 18347452
TI  - Histopathologic features of multiple myeloma involving the optic nerves.
AB  - We report a case of optic nerve involvement by multiple myeloma in which
      progressive visual loss heralded leukemic transformation and intracranial
      involvement. Imaging showed enhancing nodules in the intracranial segments of
      both optic nerves posterior to the optic canals and in the anterior optic tract,
      optic chiasm, and basal leptomeninges. Postmortem histopathologic examination
      disclosed malignant plasma cells in the subarachnoid spaces around the optic
      nerves and in the optic nerves. Infarctions were present in both optic nerves
      near their junction with the globes. Microscopic examination also showed
      malignant plasma cell infiltration of the leptomeninges of the cerebrum, brain
      stem, optic chiasm, pituitary gland, cranial bone marrow, and subarachnoid blood
      vessels. This is the first reported histopathologic examination in conjunction
      with MRI of multiple myeloma involving the anterior visual pathway. The mechanism
      of optic neuropathy in this case is probably related to infiltration of the optic
      nerve meninges by malignant plasma cells and impaired vascular supply caused by
      aggregated intraluminal plasma cells and monoclonal hypergammaglobulinemia.

PMID- 18347453
TI  - High-titer collapsin response-mediating protein-associated (CRMP-5)
      paraneoplastic optic neuropathy and Vitritis as the only clinical manifestations
      in a patient with small cell lung carcinoma.
AB  - Paraneoplastic optic neuropathy (PON) is a rare syndrome usually associated with
      small cell lung carcinoma. In the 27 rigorously reported cases, neurologic
      manifestations other than visual loss have been present in all but 2. In the
      single case in which vision improved in response to treatment of the cancer, the
      collapsin response-mediating protein (CRMP)-5 titer did not change, and the
      ophthalmic examination was not detailed. We describe a patient with optic
      neuropathy and vitritis as the only clinical manifestations of PON marked by an
      extremely high titer of CRMP-5 antibody. Treatment of the underlying small cell
      lung cancer coincided with resolution of the visual abnormalities and a dramatic
      decrease in the CRMP-5 titer.

PMID- 18347454
TI  - Improvement in visual fields in a patient with melanoma-associated retinopathy
      treated with intravenous immunoglobulin.
AB  - Melanoma-associated retinopathy (MAR) is a rare disorder characterized by
      photopsias, shimmering vision, nyctalopia, and dysfunction of rod photoreceptor
      cells. We describe a 56-year-old man with metastatic cutaneous melanoma to the
      lymph nodes and MAR. He underwent resection of the metastasis followed by
      radiation therapy. Over the ensuing 2 months, visual function worsened so he was
      treated with intravenous immunoglobulin (IVIg). Visual fields, but not
      electroretinography, improved steadily over the next year. No evidence of
      recurrence or metastatic disease has been found. Our patient indicates that even
      after a reduction or elimination of melanoma tumor burden and presumably the
      attenuation of the antigenic stimulus driving MAR, this disorder can continue to
      progress. In this setting, IVIg therapy should be considered a viable treatment
      option.

PMID- 18347455
TI  - Long-term survival in paraneoplastic opsoclonus-myoclonus syndrome associated
      with small cell lung cancer.
AB  - Paraneoplastic opsoclonus-myoclonus syndrome (OMS) is associated with small cell
      lung cancer (SCLC) in adults. Without appropriate treatment for SCLC, all
      reported patients with SCLC and OMS have died of complications of OMS within 3
      months of diagnosis. With appropriate treatment, about half of reported patients
      have had improvement in neurologic function, and several have become long-term
      survivors (6-84 months). We report a patient with SCLC who presented with OMS and
      was refractory to immunosuppressive therapy but responded rapidly to
      antineoplastic therapy and remains alive with no sign of SCLC recurrence and
      minimal residual neurologic deficits 30 months after diagnosis. In patients
      presenting with OMS, early recognition and treatment of the underlying malignancy
      probably improve the chances for recovery from the OMS with minimal deficit and
      ultimate survival.

PMID- 18347456
TI  - Third cranial nerve palsy caused by intracranial extension of a sino-orbital
      natural killer T-cell lymphoma.
AB  - Natural killer/T-cell lymphomas (NKTLs) are rare destructive lesions that usually
      involve the nasal cavity or paranasal sinuses. Orbital and intracranial
      involvement is rare. A 53-year-old man with systemic lupus erythematosus who was
      receiving chronic low-dose prednisone treatment developed proptosis of the right
      eye. Biopsy of a sino-orbital lesion suggested nonspecific inflammation. Clinical
      and imaging manifestations resolved with a higher dose of prednisone, but when
      the prednisone dose was tapered, the patient developed a complete right third
      cranial nerve palsy. Imaging showed return of the original lesion, now with
      intracranial extension and enhancement of the right third cranial nerve. Repeat
      biopsy showed features consistent with NKTL. Biopsy of this lesion in its early
      stage may misleadingly suggest a primary inflammatory disorder because of a
      paucity of neoplastic cells, a large number of inflammatory cells recruited by
      the innate natural killer (NK) cell immune response, and extensive necrosis
      caused by angiodestructive tumor cells.

PMID- 18347457
TI  - Isolated lymphoma of the anterior visual pathway diagnosed by optic nerve biopsy.
AB  - A 72-year-old previously healthy man developed rapidly progressive visual loss,
      and brain imaging showed features suggestive of a malignant glioma of the
      anterior visual pathway. Biopsy of one optic nerve yielded a diagnosis of
      lymphoma. There was no evidence of an extracranial non-Hodgkin lymphoma, so the
      conclusion was that this represented a primary central nervous system lymphoma
      (PCNSL). PCNSL isolated to the optic chiasm has been described only once in an
      immunocompetent patient. Our patient is unusual in that the lymphoma involved the
      optic nerve, chiasm, and tract in an immunocompetent patient.

PMID- 18347458
TI  - Multiple intracranial meningiomas causing papilledema and visual loss in a
      patient with nevoid Basal cell carcinoma syndrome.
AB  - A 27-year-old man with nevoid basal cell carcinoma syndrome (NBCCS, Gorlin
      syndrome) who had undergone craniospinal irradiation for a childhood brain stem
      medulloblastoma complained of progressive binocular visual loss. Ophthalmologic
      examination disclosed subnormal visual acuity and visual fields in both eyes
      attributed to chronic papilledema. Brain MRI demonstrated mass effect from
      multiple large meningiomas. After embolization and surgical resection of the
      largest meningioma, papilledema disappeared and visual dysfunction resolved
      partially. This is the sixth reported patient with NBCCS, medulloblastoma, and
      craniospinal radiation who has developed intracranial meningioma, further
      documenting the fact that such patients have a relatively high likelihood of
      developing meningiomas, especially multiple meningiomas. Because patients with
      NBCCS are often mentally impaired and because papilledema can progress silently
      before causing irreversible visual loss, periodic ophthalmologic examination is
      advisable after craniospinal radiation.

PMID- 18347459
TI  - Orbital metastasis of hepatocellular carcinoma.
AB  - We report a 74-year-old woman who presented with an orbital apex syndrome and
      pulsatile proptosis. CT showed a right orbital mass that destroyed the orbital
      sphenoid bone and extended intracranially. Biopsy revealed metastatic
      hepatocellular carcinoma (HCC), and subsequent investigations demonstrated a high
      level of serum-fetoprotein and a huge liver mass. The patient died shortly after
      the biopsy. Rarely reported in the English literature, metastatic HCC is common
      in Asia, perhaps because of a racial predisposition together with a relatively
      high prevalence of alcoholic cirrhosis, chronic hepatitis B and C, and exposure
      to aflatoxins.

PMID- 18347460
TI  - Homonymous hemianopia caused by solitary skull metastasis of hepatocellular
      carcinoma.
AB  - We report a patient who developed a complete left homonymous hemianopia from mass
      effect of a solitary skull metastasis of hepatocellular carcinoma (HCC). After
      chemoembolization and resection, the visual field defect improved markedly. This
      is the first reported case demonstrating this phenomenon in HCC. It supports
      aggressive treatment of a solitary skull metastasis in this setting.

PMID- 18347461
TI  - Presumed bilateral optic nerve sheath meningiomas presenting as optic neuritis.
AB  - A 30-year-old man who developed acute blurred vision in the right eye and right
      periocular pain on eye movement proved to have a bilateral optic neuropathy and
      imaging evidence suggestive of bilateral optic nerve sheath meningiomas. This is
      an unusual presentation for optic nerve meningioma but a reminder that this
      entity may mimic optic neuritis.

PMID- 18347462
TI  - Neuro-ophthalmologic manifestations of paraneoplastic syndromes.
AB  - Paraneoplastic syndromes with neuro-ophthalmologic manifestations may involve the
      central nervous system, cranial nerves, neuromuscular junction, optic nerve,
      uvea, or retina. Most of these disorders are related to immunologic mechanisms
      presumably triggered by the neoplastic expression of neuronal proteins. Accurate
      recognition is essential to appropriate management.

PMID- 18347463
TI  - Expanding access to published research: open access and self-archiving.
AB  - Academic libraries traditionally provide access to the life science journal
      literature for their respective institutions by purchasing annual subscriptions
      to journals. However, with skyrocketing subscription prices and decreased or
      flattened library budgets, fewer journals are being purchased. This trend results
      in diminished access to the literature for members of that institution. Open
      access and self-archiving are possible solutions to this crisis.

PMID- 18347464
TI  - Open access mandate threatens dissemination of scientific information.
AB  - The public good is served when researchers can most easily access current, high
      quality research through articles that have undergone rigorous peer review and
      quality control processes. The free market has allowed researchers excellent
      access to quality research articles through the investment of societies and
      commercial publishers in these processes for publication of scholarly journals in
      a wide variety of specialty and subspecialty areas. Government legislation
      mandating "open access" to copyrighted articles through a government Web site
      could result in a reduction of financially sustainable peer-reviewed journals and
      a reduction in the overall quality of articles available as publishers,
      societies, and authors are forced to hand over their intellectual property or
      restrict the peer review process because of lost sales opportunities. The public
      is best served when the work of researchers advances science to its benefit. If
      researchers have fewer current resources, diminished quality control, or access
      to fewer trusted peer-reviewed journals, the public could ultimately lose more
      than it could gain from open access legislation.

PMID- 18347465
TI  - Bilateral posterior ischemic optic neuropathy associated with use of sildenafil.

PMID- 18347466
TI  - Stepwise decline in visual field after serial sildenafil use.

PMID- 18347467
TI  - Intravitreal triamcinolone for nonarteritic anterior ischemic optic neuropathy.

PMID- 18347469
TI  - Animal model for nonarteritic anterior ischemic optic neuropathy.

PMID- 18347471
TI  - I am a retinal migraineur.

PMID- 18347473
TI  - Corticosteroid administration and exercise performance.

PMID- 18347475
TI  - What is a true placebo?

PMID- 18347477
TI  - Live item index technique: an intervention research tool.
AB  - BACKGROUND: Instruments commonly used in quality of life research may yield valid
      and reliable reflections of a person's state at a particular point in time. Yet,
      discrete items within those scales may be insensitive indicators for a specific
      population sample or intervention, thus creating what often appears to be chaotic
      data. OBJECTIVES: To evaluate the relative sensitivity of each item in three
      commonly used instruments for measuring quality of life in breast cancer
      survivors. METHODS: Using data from 150 breast cancer survivors, absolute change
      scores were calculated for each of 98 items comprising the three scales. A Live
      Item Index Technique score was calculated by multiplying Magnitude and Breadth
      factors for each of the 98 items. The proportion of variance that each item
      contributed was calculated, and the items were ranked in terms of sensitivity.
      RESULTS: Forty-eight "live" items accounted for 62% of total change score
      variance. The most sensitive item was over 12 times more sensitive than the least
      sensitive item. On average, live items were 1.7 times more sensitive than less
      sensitive items. DISCUSSION: If appropriate to meet study objectives, in
      designing similar studies, one may consider removing the "dead" items that never
      change. With fewer items as end point measures, the study would become more
      efficient and a smaller sample size would be needed, thereby reducing research
      cost. Also, Live Item Index Technique can be used as an exploratory and
      developmental tool for constructing more effective interventions.

PMID- 18347478
TI  - Cognitive test performance and brain pathology.
AB  - BACKGROUND: Cognitive impairment, assessed using paper-and-pencil tests, occurs
      with multiple syndromes, including heart failure; however, relationships between
      test performance and brain injury are unclear. OBJECTIVES: To determine the
      extent of brain injury assessed by magnetic resonance T2 relaxometry procedures
      in a mixed sample with cognitive impairment as measured by the Mini-Mental State
      Examination, Trailmaking Test parts A (TMT-A) and B (TMT-B), and the Watson Clock
      Drawing Test (CDT). METHODS: A comparative design was used with a convenience
      sample of 66 participants (age 48.2 +/- 8.4 years, 41 males, 52 right-handed).
      Normal and abnormal performances on cognitive tests were compared using T2
      relaxation values across the brain (p < .005). Fifty-four of the participants
      were healthy, and 12 had heart failure (New York Heart Association classes II
      III, left ventricular ejection fraction <0.40). RESULTS: All participants scored
      normally on the Mini-Mental State Examination; thus, this test was excluded from
      further analysis. Abnormal cognitive scores were found in 14-20% of the
      participants, with significant brain injury appearing in participants with
      abnormal test scores. Injured structures included frontal, temporal, parietal,
      insular, and cingulate cortices; corpus callosum; and caudate. The CDT results
      showed the greatest extent of structural injury. The TMT-A test demonstrated
      relationships to specific injury sites, whereas the TMT-B showed relationships
      only to isolated areas of damage. DISCUSSION: The findings suggest that paper-and
      pencil cognitive tests relate to injury in brain structures, with CDT values
      relating to the greatest extent of injury. Specific damage sites may correlate
      with unique tests, such as TMT-A. Specialized tests should be developed that
      would indicate neural injury in specific areas.

PMID- 18347479
TI  - Measurement of upper limb ulcers in patients with systemic sclerosis:
      reproducibility and correlation with pain, function, and quality of life.
AB  - BACKGROUND: There are a large number of studies addressing the treatment and
      assessment of chronic ulcers. Despite the fact that ischemic ulcers are frequent
      and difficult to manage in cases of systemic sclerosis, there is minimal
      literature on assessment measures regarding these wounds or on their
      reproducibility. OBJECTIVES: The aim of this study was to investigate
      intraobserver and interobserver reproducibility regarding ulcer dimension
      measurements in patients with systemic sclerosis. Correlations between pain,
      upper limb function, pinch strength, and quality of life were also determined.
      METHODS: A prospective 11-week follow-up study was carried out to assess active
      upper limb ulcers. Ulcer diameter, ulcer area, and interobserver reproducibility
      were performed weekly. Quality of life (Medical Outcomes Study 36-Item Short-Form
      Health Survey), upper limb function (disabilities of the arm, shoulder, and
      hand), pinch strength, pain, visual analog scale, and intraobserver
      reproducibility were assessed at baseline, 3, 7, and 11 weeks. RESULTS: Fifty-one
      active ulcers were recorded. Larger ulcer diameter, smaller ulcer diameter, and
      ulcer area demonstrated excellent intraobserver (r > .81, p < .001) and
      interobserver reproducibility (r > .76, p < .001). There was significant
      correlation between ulcer dimension and visual analog scale scores for pain (r =
      .42; p < .001) and some Medical Outcomes Study 36-Item Short-Form Health Survey;
      pinch strength; and disabilities of the arm, shoulder, and hand domains (r >or=
      .40; p < .01). DISCUSSION: Simple measurement instruments for the assessment of
      ischemic ulcers were reproducible in patients with SSc and correlated to other
      variables of interest for these wounds.

PMID- 18347480
TI  - Functional trajectory 6 months posthospitalization: a cohort study of older
      hospitalized patients in Taiwan.
AB  - BACKGROUND: Although it is well-recognized that hospitalization often
      precipitates functional decline in older patients, there have been few studies to
      examine these functional changes carefully over multiple points in time.
      OBJECTIVE: To describe functional trajectory during and 6 months
      posthospitalization and to ascertain the predictors that signal different classes
      of functional trajectory, using latent class analysis. METHODS: A cohort study
      was conducted on 286 older hospitalized patients who were admitted to five
      surgical-medical units at a tertiary medical center in Northern Taiwan. Results
      are reported of 241 participants who completed all four scheduled assessments
      during hospitalization (within 48 hr after admission and before discharge) and 3
      and 6 months postdischarge. Functional trajectory was measured using the Barthel
      index over four time points, and decline was defined as a reduction on the
      Barthel index scores. Demographics, comorbidities, visual impairment, medications
      taken, cognitive status, nutritional status, oral health, depressive symptoms,
      social support, surgical diagnosis, and length of stay were assessed as the
      predictors of functional trajectory classes. RESULTS: Most (74.3%) participants
      developed functional decline during hospitalization, and 32.0% had persistent
      functional impairment at 6 months posthospitalization. Three functional
      trajectory classes (good, moderate, and poor) were identified, and gender, age,
      comorbidities, cognitive status, nutritional status, oral health status, and
      length of stay were associated with different trajectory classes. CONCLUSION:
      Visualizing different classes of functional trajectory and studying predictors
      that signal such differences during and posthospitalization help practitioners
      understand how function changed and the possible ways to intervene.

PMID- 18347481
TI  - The validity and reliability of a Spanish version of the summary of diabetes self
      care activities questionnaire.
AB  - BACKGROUND: Translation of data collection instruments, paying careful attention
      to equivalency between the source and the target language, is important to obtain
      valid data collection instruments. OBJECTIVE: To translate the Summary of
      Diabetes Self-Care Activities (SDSCA) questionnaire (English) into Spanish and to
      evaluate the reliability and validity of the Spanish version. METHODS:
      Translation and back-translation were used to develop the Spanish version of the
      SDSCA. The Spanish version of the SDSCA was reviewed by an expert panel for
      conceptual and content equivalence to the English version. Psychometric
      properties were assessed further by combining data from three studies that used
      the Spanish version as a data collection instrument. RESULTS: Correlation of each
      item of the Spanish and English version of the SDSCA instrument ranged from .78
      to 1.00, with no variability in the responses of 2 of the 12 items. Test-retest
      correlations for the SDSCA ranged from .51 to 1.00. Internal consistency
      (Cronbach's alpha) for the Spanish version was .68. Items loaded on three
      factors, with the factors accounting for 61% of the variance in SDSCA.
      DISCUSSION: The findings for the psychometric properties of the Spanish version
      of the SDSCA questionnaire suggest that it has conceptual and content equivalency
      with the original English version and is valid and reliable. However, further
      testing with larger samples is required.

PMID- 18347482
TI  - Improving patient-clinician communication about chronic conditions: description
      of an internet-based nurse E-coach intervention.
AB  - BACKGROUND: Studies show that patients who have higher self-efficacy and
      participate actively in their care have better disease management. Patient
      provider Internet portals offer an exciting new venue for empowering and engaging
      patients in better management of chronic conditions. OBJECTIVES: To describe
      development of an Internet-based health coaching intervention. APPROACH: An
      Internet-based health coaching intervention to enhance patient-provider
      communication regarding three common conditions, chronic pain, depression, and
      impaired mobility, was developed. Using principles of self-management, the
      intervention aimed to engage and empower patients to collaborate with their
      primary care physician in managing their health conditions. Delivered online by
      nurse electronic coaches (e-coaches), the intervention involved a standardized
      set of e-mails and worksheets targeting self-efficacy, patient education, and
      motivation to improve health. RESULTS: Participants in the intervention (N = 121)
      primarily used the automated elements of the program, although 35% exchanged e
      mails with the nurse e-coach. Most patients (88%) who contacted the e-coach were
      interested in further coaching. Patients who viewed the online worksheets did so
      repeatedly; 42 patients opened the worksheets 107 times prior to the visit.
      DISCUSSION: The Internet-based coaching intervention departs substantially from
      usual nursing care but warrants further study given its potential to offer
      considerable benefits to large numbers of patients. Several challenges were
      identified to providing patient coaching and self-management support via the
      Internet, but this efficient and low-cost approach offers an innovative
      opportunity to improve patient-clinician partnerships in managing chronic
      conditions. As patients become more accustomed to electronic communication,
      nurses can play an important role, joining efforts to develop this new realm to
      promote patients as partners in managing their health conditions.

PMID- 18347483
TI  - From text to codings: intercoder reliability assessment in qualitative content
      analysis.
AB  - BACKGROUND: High intercoder reliability (ICR) is required in qualitative content
      analysis for assuring quality when more than one coder is involved in data
      analysis. The literature is short of standardized procedures for ICR procedures
      in qualitative content analysis. OBJECTIVE: To illustrate how ICR assessment can
      be used to improve codings in qualitative content analysis. METHODS: Key steps of
      the procedure are presented, drawing on data from a qualitative study on
      patients' perspectives on low back pain. RESULTS: First, a coding scheme was
      developed using a comprehensive inductive and deductive approach. Second, 10
      transcripts were coded independently by two researchers, and ICR was calculated.
      A resulting kappa value of .67 can be regarded as satisfactory to solid.
      Moreover, varying agreement rates helped to identify problems in the coding
      scheme. Low agreement rates, for instance, indicated that respective codes were
      defined too broadly and would need clarification. In a third step, the results of
      the analysis were used to improve the coding scheme, leading to consistent and
      high-quality results. DISCUSSION: The quantitative approach of ICR assessment is
      a viable instrument for quality assurance in qualitative content analysis. Kappa
      values and close inspection of agreement rates help to estimate and increase
      quality of codings. This approach facilitates good practice in coding and
      enhances credibility of analysis, especially when large samples are interviewed,
      different coders are involved, and quantitative results are presented.

PMID- 18347484
TI  - SAS macros for testing statistical mediation in data with binary mediators or
      outcomes.
AB  - BACKGROUND: Statistical mediation is an important tool in behavioral health
      sciences, but it has been confined primarily to continuous variables. As
      prevention studies become increasingly common, more often the mediator or outcome
      is binary. Recent work by D. P. MacKinnon and J. H. Dwyer (1993) has explicated
      the steps necessary to estimate models for mediation when the mediator or the
      outcome is binary. OBJECTIVE: To report the release of a set of SAS macros used
      to implement the statistical analyses required to analyze data with binary and
      continuous-level data. APPROACH: A brief introduction to the methodology of
      mediation analysis in the presence of a binary outcome, mediator, or both is
      provided. The macros are tested on a sample of 84 participants who were
      experiencing pain. It is hypothesized that the relationship between pain and
      fatigue is mediated by sleep disturbance. RESULTS: The relationship between pain
      and fatigue was mediated by the presence of sleep disturbances, and the amount of
      mediation was 23.34%. DISCUSSION: The SAS macros are available for download
      without charge from the second author's Web site. Instructions are provided in an
      included technical manual.

PMID- 18347485
TI  - Tobacco intervention attitudes and practices among certified registered nurse
      anesthetists.
AB  - BACKGROUND: The period before surgery represents an opportunity for perioperative
      nurses, including certified registered nurse anesthetists (CRNAs), to address the
      tobacco use of their patients. OBJECTIVE: To assess the current practices and
      attitudes of CRNAs toward tobacco interventions. METHODS: A survey assessing
      current attitudes, practices and beliefs, and respondent demographics was mailed
      to 1,000 practicing CRNAs randomly selected from the membership of the American
      Association of Nurse Anesthetists, with one follow-up reminder. Summary
      statistics of survey responses were prepared. RESULTS: The response rate was 44%
      (N = 439). Almost all respondents (92%) reported routinely asking their patients
      if they smoke cigarettes, and the majority felt that it was their responsibility
      to advise their patients to quit smoking. However, most do not routinely do so.
      Identified barriers to intervention included a lack of time to intervene and a
      lack of training. Interest in learning more about tobacco interventions was high,
      with strong majorities willing to take an extra 5 minutes preoperatively to
      intervene and to refer patients to other intervention services. DISCUSSION: These
      results can inform efforts to promote tobacco use interventions in surgical
      patients by CRNAs. Increasing the frequency and effectiveness of tobacco use
      interventions provided by CRNAs would benefit not only immediate perioperative
      outcomes, but also the long-term health of surgical patients who take advantage
      of the surgical episode to initiate long-term tobacco abstinence.

PMID- 18347487
TI  - Tertiary pediatric emergency department admission rates fall as waiting times
      increase.
AB  - OBJECTIVES: To examine whether children in the same triage category presenting to
      a tertiary paediatric emergency department are more likely to be admitted to
      hospital if their wait is longer. METHODS: Retrospectively during a 7-year
      period, we determined the admission rate of children with lower acuity triage
      scores and compared 3 groups; those seen in their recommended triage time (group
      A), those seen under twice their recommended time (group B), and those seen in
      over twice their recommended time (group C). RESULTS: Patients in groups B and C
      were less likely to be admitted for both triage categories 3 and 4 compared with
      group A (P < 0.005 for all admission rate comparisons). This held true in
      individual diagnostic groups. CONCLUSIONS: Predictably, but reassuringly, those
      patients waiting longer than the recommended category time are no more likely to
      get admitted and do not represent a grossly different subset of patients in terms
      of age and diagnosis. Further work is needed to identify, at the point of triage,
      the characteristics of children who are unlikely to deteriorate during their
      wait.

PMID- 18347488
TI  - Randomized trial of a case management program for assault-injured youth: impact
      on service utilization and risk for reinjury.
AB  - OBJECTIVES: The purposes of this study were to (1) assess receptiveness of
      families to violence prevention interventions initiated after an assault injury
      and (2) assess the effectiveness of a case management program on increasing
      service utilization and reducing risk factors for reinjury among assault-injured
      youth presenting to the emergency department. DESIGN/METHODS: A randomized
      controlled trial of youth, aged 12 to 17 years, presenting to a large urban
      hospital with peer assault injury was conducted. Youth and parents were
      interviewed at baseline and 6 months to measure service utilization, risk
      behavior, attitudes about violence, mental health, and injury history.
      INTERVENTION: Intervention families received case management services by
      telephone or in person during 4 months by a counselor who discussed sequelae of
      assault injury and assessed family needs and facilitated service use. Controls
      received a list of community resources. RESULTS: Eighty-eight families were
      enrolled; 50 (57%) completed both youth and parent follow-up interviews.
      Intervention and control groups were not significantly different at baseline on
      demographics, service utilization, and risk factors. Fighting was common in both
      groups. Most parents and youth identified service needs at baseline, with
      recreational programs, educational services, mentoring, and counseling as most
      frequently desired. There was no significant program effect on service
      utilization or risk factors for injury. Although intervention families were
      satisfied with case management services, there was no significant increase in
      service utilization compared with controls. CONCLUSIONS: Youth and parents were
      receptive to this violence prevention intervention initiated after an emergency
      department visit. This pilot case management program, however, did not increase
      service utilization or significantly reduce risk factors for injury. More
      intensive violence prevention strategies are needed to address the needs of
      assault-injured youths and their families.

PMID- 18347489
TI  - Cosmetic outcomes of absorbable versus nonabsorbable sutures in pediatric facial
      lacerations.
AB  - OBJECTIVES: We sought to compare the long-term cosmetic outcomes of absorbable
      versus nonabsorbable sutures for facial lacerations in children and to compare
      the complication rates and parental satisfaction in the 2 groups. DESIGN/METHODS:
      Healthy patients presenting to a pediatric emergency department with facial
      lacerations were randomized to repair using fast-absorbing catgut or nylon
      suture. Patients were followed up at 5 to 7 days and at 3 months. Three blinded
      observers, using a previously validated 100-mm cosmesis visual analogue scale
      (VAS) as the primary instrument, rated photographs of the wound taken at 3
      months. For this noninferiority study, a VAS score of 15 mm or greater was
      considered to be the minimal clinically important difference. Parents also rated
      the wound using the VAS and completed a satisfaction survey. RESULTS: Of the 88
      patients initially enrolled, 47 patients completed the study: 23 in the catgut
      group and 24 in the nylon group. There were no significant differences in age,
      race, sex, wound length, number of sutures, and layered repair rates in the 2
      groups. The observers' mean VAS for the catgut group was 92.3 (95% confidence
      interval [CI], 89.1-95.4) and that for the nylon group was 93.7 (95% CI, 91.4
      96.0), with a difference of the means of 1.4 (95% CI, -5.31 to 8.15), which was
      less than the minimal clinically important difference of 15 mm (power, >90%). The
      mean parental VAS score for the catgut group was 86.3 (95% CI, 78.4-94.1) and
      that for the nylon group was 91.2 (95% CI, 86.9-95.4), with a difference of the
      means of 4.9 (95% CI, 2.41-7.41), also less than 15 mm. There were no significant
      differences in the rates of infection, wound dehiscence, keloid formation, and
      parental satisfaction. CONCLUSIONS: The use of fast-absorbing catgut suture is a
      viable alternative to nonabsorbable suture in the repair of facial lacerations in
      children.

PMID- 18347490
TI  - Derivation of the DIVA score: a clinical prediction rule for the identification
      of children with difficult intravenous access.
AB  - OBJECTIVE: To develop a clinical prediction rule that would be easy to apply and
      be useful for predicting success or failure of peripheral intravenous line
      insertion in children. METHODS: This was a prospective cohort study of children
      aged 0 to 21 years undergoing peripheral intravenous placement by staff nurses in
      a pediatric emergency department. Information on candidate predictor variables
      was obtained before attempting intravenous placement, and the outcome was
      successful on first attempt. Backward stepwise logistic regression was used to
      identify factors independently predictive of success. Those factors remaining in
      the model were used in a set of linear scores. Receiver operating characteristic
      curves were constructed for each model, and the areas under the curve were
      calculated. RESULTS: Six hundred fifteen subjects were enrolled. Success rate for
      intravenous insertion on first attempt was 75%. A 4-variable proportionally
      weighted rule (known as the difficult intravenous access [DIVA] score) was
      created (3 points for prematurity, 3 for younger than 1 year, 1 for 1-2 years of
      age, 2 for vein not palpable, and 2 for vein not visible). The area under the
      receiver operating characteristic curve was 0.67. Subjects with a DIVA score of 4
      or more were more than 50% likely to have failed intravenous placement on first
      attempt. CONCLUSIONS: A clinical prediction rule that is easy to apply and is
      useful for predicting success or failure of peripheral intravenous insertion has
      been created. If externally validated, this DIVA score can be used to predict
      which children will have difficult intravenous access.

PMID- 18347491
TI  - Pediatric fingertip injuries: do prophylactic antibiotics alter infection rates?
AB  - STUDY OBJECTIVE: Fingertip injuries are common in the pediatric population.
      Considerable controversy exists as to whether prophylactic antibiotics are
      necessary after repair of these injuries. Our goal was to compare the rate of
      bacterial infections among subgroups treated with and without prophylactic
      antibiotics. The study hypothesis was that infection rates were similar in the 2
      groups. METHODS: This was a prospective randomized control trial of pediatric
      patients presenting to an urban children's hospital with trauma to the distal
      fingertip, requiring repair. Patients were randomized to 2 groups: group 1
      received no antibiotics, and group 2 received antibiotics (cephalexin). Repairs
      were performed in a standardized fashion, and all patients were reevaluated in
      the same emergency department in 48 hours and again by phone 7 days after repair.
      The primary outcome measure was the rate of infection at 7 days after repair.
      RESULTS: One hundred forty-six patients were initially enrolled in the study, 11
      patients were withdrawn before study completion, 69 subjects were randomized to
      the no-antibiotic group, and 66 subjects were randomized to the antibiotic group.
      There was 1 infection in each group at 7 days after repair. The infection rate
      was 1.45% (95% confidence interval, 0.04%-7.81%) for the no-antibiotic group and
      was 1.52% (95% confidence interval, 0.04%-8.16%) for the antibiotic group, not
      statistically significant (P = 1.00). CONCLUSIONS: This study suggests that
      routine prophylactic antibiotics do not reduce the rate of infection after repair
      of distal fingertip injuries.

PMID- 18347492
TI  - Contents of referral letters to the children emergency unit of a teaching
      hospital, southwest of Nigeria.
AB  - OBJECTIVE: This study was carried out to evaluate the quality of the contents of
      referral letters received at the pediatric emergency unit of the University
      College Hospital, Ibadan, Nigeria. DESIGN: We prospectively reviewed consecutive
      referral letters received over a 6-month period. The details of the contents of
      each letter were recorded using a structured pro-forma by 2 of the investigators
      after consent was obtained from the parent or caregiver. RESULTS: There were 974
      patients admitted with referral letters; this accounted for 54.8% of all
      admissions. There were 568 boys and 406 girls (ratio, 1.4:1). More than one tenth
      of the referred patients reported after 24 hours of writing the letters. Letters
      were written by physicians (69.2%), registered nurses (21.3%), hospital
      assistants (2.1%), traditional birth attendants (0.4%), and non-health workers
      (0.3%). The identity of the writers of 65 letters (6.7%) could not be defined.
      More than half of the letters did not contain the patients' age, the treatment
      given, the findings from the investigations performed, the medical history, and
      what the writers expect from the referral. Other missing information includes
      examination findings (47.9%), provisional diagnosis (38.6%), history of
      presenting complaints (36.6%), writers' addresses (32.5%), reasons for the
      referral (23.9%), patients' sex (20.1%), and patients' names (3.4%). The most
      frequently stated reason for referral was poor or no response to the treatment
      given (17.8%). CONCLUSION: The contents of referral letters from the general
      practitioners to the pediatric emergency unit were found to be grossly
      inadequate. To enhance the quality of correspondence between the referring
      physicians and pediatricians, there may be a need for training and introduction
      of letter-format prompt forms.

PMID- 18347493
TI  - Profound hypokalemia: unusual presentation and management in a 12-year-old boy.
AB  - Hypokalemia is a frequent electrolyte abnormality that rarely requires more than
      oral supplementation to correct. We describe a case of profound hypokalemia and
      cardiac arrhythmia requiring unusually large amounts of "bolused" potassium to
      restore to normal sinus rhythm. Our patient presented with significant
      dehydration and electrolyte abnormalities after several days of emesis. Most
      alarming of these findings was a serum potassium level of 1.2 mEq/L. The
      electrocardiogram showed changes consistent with hypokalemia that rapidly
      degraded into pulseless ventricular tachycardia. Potassium chloride of 140 mEq
      was hand-pushed during the resuscitation with return of spontaneous rhythm. The
      patient was discharge 11 days later in his prearrest state.

PMID- 18347494
TI  - Misuse of an adult seat belt in a 7-year-old child: a source of dramatic injuries
      and a plea for booster seat use.
AB  - Children involved in high-speed vehicle collision could be particularly exposed
      to severe injuries when adult restraints are used. We report a case where adult 3
      point restraint used without booster seat was responsible for severe thoracic
      injury resulting in complete shoulder and clavicle dislocation, occipito-atloidal
      dislocation, and complete disruption of right common carotid artery in a 7-year
      old boy. Misplacement of the adult shoulder harness at the base of the neck could
      be directly responsible for these lethal injuries, which could probably be
      avoided by concomitant use of a booster seat.

PMID- 18347495
TI  - Scimitar syndrome: an uncommon cause of wheezing.
AB  - Scimitar syndrome is a rare congenital anomaly characterized by total or partial
      anomalous venous drainage of the right lung to the inferior vena cava. The
      infantile form presents with congestive heart failure and respiratory distress in
      early months of life. We report here the case of a 6-month-old male child who
      presented with second episode of respiratory distress and wheeze. Poor response
      to bronchodilators led to fibreoptic bronchoscopy and computed tomographic scan
      that revealed bronchial anomalies with aberrant drainage of right lung into the
      inferior vena cava by scimitar vein. The case illustrates that one of the rare
      causes of wheezing in an infant could be scimitar syndrome.

PMID- 18347496
TI  - Central alpha-2 adrenergic eye drops: case series of 3 pediatric systemic
      poisonings.
AB  - Three pediatric patients presented with systemic central alpha-2 agonist
      poisoning-2 cases of bradycardia and apnea resulting from ingestion of ingestion
      of apraclonidine, with 1 case requiring intubation, and 1 case of bradycardia and
      altered mental status requiring intensive care monitoring resulting from
      therapeutic ophthalmic application of brimonidine. Pediatric poisonings involving
      central alpha-2 adrenergic agonists have been well described, particularly with
      the prototypical agent clonidine. Characteristic symptoms include sympatholytic
      effects such as central nervous system depression, respiratory depression,
      hypotension, bradycardia, miosis, hypothermia, and hyporeflexia. Although
      structurally similar to clonidine, these compounds are presumed to be safer for
      pediatric use because they are more polar and less lipophilic than clonidine,
      thereby limiting their ability to cross the blood-brain barrier and reducing
      incidence of centrally mediated effects. Systemic toxicities of alpha-2 agonist
      ophthalmic preparations in pediatric patients are similar to those seen with
      clonidine poisonings. Symptomatic patients should be treated in the same manner
      as patients with clonidine poisoning. Treatment of systemic poisoning is
      primarily supportive. Periodic tactile stimulation seems to be an effective
      nonpharmacological intervention to improve alpha-2 adrenergic agonist-induced
      central nervous system depression and respiratory depression. Intubation should
      be considered when tactile stimulation is not effective.

PMID- 18347497
TI  - Alcoholic ketoacidosis in an 11-year-old boy.
AB  - A history of ethanol consumption combined with vomiting, anion gap metabolic
      acidosis, and altered mental status is consistent with a broad differential
      diagnosis, which requires a systematic approach. Alcoholic ketoacidosis is rare
      after binge drinking in the naive individual and typically occurs in patients
      with heavy, chronic use. We present the case of an 11-year-old boy with acute
      ethanol intoxication and a clinical course that is most consistent with alcoholic
      ketoacidosis. Alcoholic ketoacidosis should be considered in the differential
      diagnosis of children with unexplained ketoacidosis when there is history or
      evidence of ethanol consumption combined with the appropriate clinical
      presentation.

PMID- 18347498
TI  - Management of pediatric penetrating oropharyngeal trauma.
AB  - Penetrating oropharyngeal trauma (OPT) is common in young children. Complications
      are rare but can be severe and with delayed onset. Controversy exists about the
      evaluation and management of OPT, although most injuries in the stable child can
      be managed in the outpatient setting. Two pediatric OPT cases and a brief review
      of the literature are presented.

PMID- 18347499
TI  - Gastrointestinal decontamination of the poisoned patient.
AB  - Gastrointestinal decontamination has been a historically accepted modality in the
      emergency management of oral intoxicants. Theoretically, gastric and whole-bowel
      emptying procedures hinder absorption, remove toxic substances, prevent clinical
      deterioration, and hasten recovery. This article presents a current overview of
      gastrointestinal decontamination. It challenges the accepted precepts of gut
      decontamination and assesses the utility of syrup of ipecac-induced emesis,
      orogastric lavage, single-dose-activated charcoal, cathartics, and whole-bowel
      irrigation.

PMID- 18347501
TI  - Skimboarding: fall on shoulder-pain.

PMID- 18347502
TI  - An unsteady walk in the park.

PMID- 18347503
TI  - ECGs in the ED.

PMID- 18347504
TI  - Maintaining a high index of suspicion for carbon monoxide poisoning is life
      saving.

PMID- 18347505
TI  - Treatment of tricyclic antidepressant cardiac toxicity.

PMID- 18347506
TI  - Ependymal tumors with sarcomatous change ("ependymosarcoma"): a clinicopathologic
      and molecular cytogenetic study.
AB  - Gliosarcomas are uncommon primary tumors of the central nervous system defined as
      exhibiting both glial and sarcomatous components. Sarcomatous change occurring in
      ependymal tumors is rare. We identified 11 such examples. There were 6 female and
      5 male patients (median age, 18 y; range, 2 to 63). The tumors were located in
      the parieto-occipital (n=2), temporal (n=1), parietal (n=1), frontal (n=1), and
      occipital lobes (n=1), as well as the lateral ventricles (n=2), insula (n=1),
      cerebellopontine angle (n=1), and fourth ventricle/cerebellopontine angle (n=1).
      At presentation, the sarcomatous component was noted in 6 (of 10) cases and the
      ependymal element was grade III in 7 and grade II in 3 tumors, respectively. The
      sarcomatous component consisted of a reticulin rich, glial fibrillary acidic
      protein-negative fibrosarcoma (n=5) or pleomorphic spindle cell sarcoma (n=3),
      and 2 examples with heterologous elements: osseous and cartilaginous (n=1) and
      osseous only (n=1). The single case involving the fourth ventricle/left
      cerebellopontine angle consisted of subependymoma and fibrosarcoma components in
      roughly equal proportions at presentation. Fluorescence in situ hybridization
      studies performed with probes targeting the NF2 gene and other members of the
      protein 4.1 gene family demonstrated similar alterations in the ependymal and
      sarcomatous components in the cases tested, including polysomies/polyploidy
      (n=3), gains of 1q (n=3), deletions of 22q (n=2) and 6q (n=1), and monosomy 18
      (n=1). There was no evidence of MDM2 or CCND1 amplification in any of the cases
      tested. On follow-up, 5 patients expired 4 months to 18 years after initial
      resection and 4 to 11 months after development of the sarcomatous component
      (mean, 7.6 mo); 1 patient is alive at 5 years with recurrent disease, and 1 is
      alive without recurrence 12 years after initial gross total resection followed by
      radiation therapy. Although rare, ependymal neoplasms must be included among the
      gliomas prone to undergo sarcomatous change and we propose the term
      "ependymosarcoma" for these tumors.

PMID- 18347507
TI  - Diagnosing endometrial hyperplasia: why is it so difficult to agree?
AB  - Current World Health Organization classification of endometrial hyperplasia is
      problematic because of poor diagnostic reproducibility. We sought to determine
      factors that cause diagnostic disagreement in a review of 2601 endometrial
      specimens. Blinded random specimens of normal endometrium, hyperplasias, and
      carcinoma were reviewed by 2 pathologists, with review by a third pathologist in
      cases with disagreement. All cases of endometrial hyperplasia or carcinoma were
      scored for degree of glandular crowding, architectural complexity, and cytologic
      atypia. Sample adequacy, hyperplasia volume, presence of metaplasia, or
      endometrial polyp were also scored. The overall kappa for agreement was 0.71,
      with a lower kappa of 0.36 when cases called "no hyperplasia" were excluded. The
      percent specific agreement was 90.3% for no hyperplasia, 31.1% for simple
      hyperplasia, 51.1% for complex hyperplasia, 49.8% for atypical hyperplasia, and
      57.5% for adenocarcinoma. Cases categorized as "low volume hyperplasia" had more
      diagnostic disagreement than "high volume," (62% vs. 39%, P=0.003). Similarly,
      cases called "scant" had more diagnostic disagreement than "not scant" (65% vs.
      57%, P=0.013). The histologic feature associated with the most diagnostic
      disagreement was cytologic atypia (P<0.0001). Architectural crowding,
      architectural complexity, or the presence of a polyp were all associated with
      diagnostic disagreement (P<0.0001). High diagnostic disagreement in endometrial
      hyperplasia is related to both sample adequacy and interpretation of histologic
      features present. Although obtaining additional tissue may increase diagnostic
      reproducibility, differences in interpretation of key histologic features like
      cytologic atypia remain major factors contributing to diagnostic disagreement.

PMID- 18347508
TI  - Primary cutaneous apocrine carcinoma: a clinico-pathologic analysis of 24 cases.
AB  - Primary cutaneous apocrine carcinoma is a rare malignancy. This study of 24
      examples suggests that the prognosis is not always poor and that grading criteria
      devised for breast carcinoma may have utility in this group of malignancies.
      Furthermore, steroid receptor expression should be investigated in these tumors,
      particularly if a tumor is unlikely to be controlled by surgery alone.

PMID- 18347509
TI  - Assessment and grading of mucosal inflammation in colonic diverticular disease.
AB  - GOAL: The aim of this study was to assess and grade the mucosal inflammatory
      infiltrate in different degrees of diverticular disease (DD) and to compare them
      with healthy matched controls. BACKGROUND: Mucosal inflammation in colonic DD has
      never been investigated. In particular, it is unknown whether inflammation may be
      found in every degree of DD. MATERIALS AND METHODS: Thirty consecutive patients
      with a new endoscopic diagnosis of DD (10 with asymptomatic diverticulosis, 10
      with symptomatic uncomplicated DD, and 10 with acute uncomplicated
      diverticulitis) and 10 healthy controls were studied. RESULTS: A neutrophilic
      inflammatory infiltrate was found only in acute uncomplicated diverticulitis
      (overall score, 26). The mean lymphocytic cell density was significantly higher
      in symptomatic DD (median lymphocytic density, 7) and acute uncomplicated
      diverticulitis (median lymphocytic density, 11). Subdividing the patients
      according to different degrees of DD, we found higher lymphocytic cell density
      even in asymptomatic diverticulosis (median lymphocytic density, 6.5) than
      healthy controls (median lymphocytic density, 4; P<0.02). CONCLUSIONS: We found
      an increased inflammatory infiltrate in DD according to the degree of the disease
      and higher than healthy controls. Moreover, also asymptomatic diverticulosis
      shows higher inflammatory cell density than controls.

PMID- 18347510
TI  - Validation of a graded response questionnaire for the diagnosis of
      gastroesophageal reflux disease in an Asian primary care population.
AB  - BACKGROUND: Diagnosis of gastroesophageal reflux disease (GERD) based on
      subjective evaluation of symptoms alone is challenging. GOALS: To test the
      validity and reliability of a graded response questionnaire to identify patients
      with GERD. STUDY: Patients presenting with upper abdominal symptoms for more than
      a month, and without alarm features were consecutively recruited. They completed
      a 12-item questionnaire encompassing 6 symptoms presented either in Chinese or
      English language. Scores were analyzed for validity in diagnosis of GERD, using
      gastroenterologist's diagnosis as reference standard. Receiver operating
      characteristic (ROC) analysis, predictive values, likelihood ratios, and
      diagnostic odds ratio were used to evaluate diagnostic accuracy. RESULTS: Of 209
      patients studied, 163 (78%) answered the English whereas 45 (21.5%) answered the
      Chinese version. At a cut-off of > or =28.5 in total symptom scores, the Chinese
      version had a sensitivity of 87.5% and specificity of 75.7% with an area under
      the ROC curve (AUCROC) of 0.824 for diagnosis of GERD. Corresponding sensitivity
      and specificity for the English version were 76.9% and 50.8%, respectively, with
      an AUCROC of 0.760. Positive predictive value, negative predictive value,
      positive likelihood ratio (+LR), negative likelihood ratio (-LR), and diagnostic
      odds ratio were 0.438, 0.966, 3.597, 0.165, and 21.778 and 0.330, 0.875, 1.564,
      0.454, and 3.443 for the Chinese and English versions, respectively. CONCLUSIONS:
      The questionnaires demonstrated good construct reliability, which were highly
      sensitive and reasonably specific for the detection of GERD. They are useful
      tools to help primary care physicians in identifying GERD in patients presenting
      with uninvestigated upper abdominal symptoms.

PMID- 18347511
TI  - Associations of circulating adiponectin with estradiol and monocyte chemotactic
      protein-1 in postmenopausal women.
AB  - OBJECTIVE: The aim of the present study was to clarify the association of serum
      adiponectin concentrations with serum 17beta-estradiol concentrations in pre-,
      peri-, and postmenopausal women. In addition, the associations of serum
      adiponectin with serum concentrations of proinflammatory and anti-inflammatory
      cytokines were examined in women during the menopausal transition. DESIGN: A
      total of 197 women were enrolled in this study: 33 premenopausal women, 80
      perimenopausal women, and 84 postmenopausal women. Serum adiponectin
      concentration was measured by an enzyme-linked immunosorbent assay. Serum
      concentrations of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and
      tumor necrosis factor alpha, anti-inflammatory cytokine IL-10, and the chemokines
      IL-8, macrophage inflammatory protein-1beta and monocyte chemotactic protein-1
      were measured by using a multiplexed human cytokine assay. RESULTS: Serum
      adiponectin concentration showed a significant negative correlation with serum
      estradiol concentration (r= -0.400, P=0.001) in postmenopausal women but not in
      pre- and perimenopausal women, and this correlation was significant after
      adjustment for age and body mass index. Serum adiponectin concentration also
      showed a significant negative correlation with serum monocyte chemotactic protein
      1 concentration (r= -0.244, P=0.05) in postmenopausal women. CONCLUSION: An
      increase in adiponectin level due to a decrease in estradiol results in a
      reduction in monocyte chemotactic protein-1 level in postmenopausal women,
      suggesting that adiponectin may be associated with a protective role against
      insulin resistance and atherosclerosis, which occur in the postmenopausal stage.

PMID- 18347512
TI  - Detection sensitivity of a commercial lung nodule CAD system in a series of
      pathologically proven lung cancers.
AB  - PURPOSE: To evaluate the performance of a commercially available computer-aided
      detection (CAD) system in a series of pathologically proven lung cancers.
      MATERIALS AND METHODS: Sixty-nine chest computed tomography (CT) scans obtained
      in 12 subjects (8 females, 4 males, age 51 to 75 y, mean 63 y) with 15
      pathologically proven lung cancers were retrospectively selected from 2156 entry
      and follow-up CT scans from a lung cancer screening program. CT scans were
      retrospectively analyzed using a commercially available CAD system for detecting
      lung nodules. RESULTS: When first detectable proven lung cancer nodules ranged in
      maximum diameter from 3 to 38 mm (10.4+/-9.2 mm) with CAD detection sensitivity
      stratified by size: 0/2 (0%) < or =3 mm, 5/8 (62.5%) 4 to 10 mm, 2/3 (66.7%) 11
      to 15 mm, 0/0 16 to 20 mm, 2/2 (100%) >20 mm, and overall sensitivity 9/15 (60%).
      The sensitivity for all CT scans (first detectable and follow-up), stratified by
      nodule size as above, was, respectively, 0/2, 18/25, 24/28, 6/9, 5/5, and overall
      53/69 (76.8%). Excluding nodules <4 mm and pure ground-glass nodules, the
      sensitivity for all CT scans by size was 18/24 (75%) 4 to 10 mm, 21/22 (95.4%) 11
      to 15 mm, 6/6 (100%) 16 to 20 mm, 5/5 (100%) >20 mm, and overall 50/57 (87.7%).
      At resection (13) or biopsy (2) nodules were: adenocarcinoma (10), squamous cell
      carcinoma (3), and small cell carcinoma (2). CONCLUSIONS: The CAD system showed
      good sensitivity for solid and semisolid cancers > or =4 mm (sensitivity 87.7%)
      and excellent for those > or =11 mm (sensitivity >95.4%).

PMID- 18347513
TI  - CT-guided biopsy of nonresolving focal air space consolidation.
AB  - OBJECTIVES: To evaluate the diagnostic accuracy of percutaneous computed
      tomography (CT)-guided coaxial core needle biopsy in patients with nonresolving
      pulmonary focal air space consolidations and negative fiberoptic bronchoscopy
      results. METHODS: From 1997 to 2005, 23 patients (11 woman, 12 men; age range, 45
      to 81 y; mean age, 66 y) presenting with nonresolving pneumonia persisting more
      than 8 weeks (mean, 22 wk; range, 8 to 40 wk) with negative fiberscopic results,
      underwent coaxial percutaneous biopsy using an automated core needle (18-gauge)
      under CT guidance. Histologic and bacteriologic evaluations were obtained. The
      final diagnosis was confirmed by surgical pathology, culture results, or clinical
      follow-up. RESULTS: Specimens adequate for histopathologic evaluations were
      obtained in 20 (87%) cases. Final diagnoses were lung cancer (n=15) and benign
      diseases (infectious pneumonia, 3; lipoid pneumonia, 1; Erdheim Chester disease:
      1; and nonspecific chronic pneumonia, 3). Diagnostic yield of core needle biopsy
      was 78% (18 of 23). The sensitivity and specificity for malignancy were 87% and
      100%, respectively. Immediate pneumothorax was present in 11 patients of cases,
      but only 2 patients required pleural drainage. DISCUSSION: CT-guided lung biopsy
      using a core needle biopsy provides a high degree of diagnostic accuracy and
      allows specific characterization of nonresolving pulmonary focal air space
      consolidation.

PMID- 18347514
TI  - Community-acquired methicillin-resistant Staphylococcus aureus pneumonia:
      radiographic and computed tomography findings.
AB  - OBJECTIVE: The aim of our study was to review the radiologic findings of
      community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
      pneumonia. MATERIALS AND METHODS: The hospital infection control computer
      database was used to identify patients who had a CA-MRSA infection with organisms
      isolated from blood, bronchoalveolar lavage fluid, or pleural fluid samples.
      Criteria for CA-MRSA pneumonia were consolidation seen on chest radiography or
      computed tomography (CT), growth of MRSA from sputum and/or sterile pulmonary
      site, clinical complaints of cough and/or shortness of breath. Chest radiographs
      and CT scans for 9 patients (5 men, mean age 45 y, range 35 to 71 y) were
      retrospectively reviewed by 2 chest radiologists. RESULTS: The most common chest
      radiographic finding was consolidation, which was bilateral in 7 patients and
      unilateral in 2 patients. The consolidation was patchy and nonsegmental in 5 and
      segmental in 4 patients. Two patients had cavitation evident on the chest
      radiograph. The most common CT scan findings were bilateral (n=8), often
      symmetric (n=5) consolidation, bilateral septal lines (n=7), and multiple nodules
      (n=5). Cavitation was present in 5 patients, either in regions of consolidation
      (n=5) or in large nodules (n=3). Five patients with CA-MRSA pneumonia had rapid
      clinical deterioration requiring ventilatory support. Two patients died.
      CONCLUSIONS: CA-MRSA pneumonia is characterized by extensive bilateral
      consolidation and frequent cavitation and is commonly associated with rapid
      progression and clinical deterioration. CT is superior to radiography in
      demonstrating the presence of cavitation.

PMID- 18347515
TI  - Postmortem imaging of blunt chest trauma using CT and MRI: comparison with
      autopsy.
AB  - OBJECTIVE: Postmortem examination of chest trauma is an important domain in
      forensic medicine, which is today performed using autopsy. Since the
      implementation of cross-sectional imaging methods in forensic medicine such as
      computed tomography (CT) and magnetic resonance imaging (MRI), a number of
      advantages in comparison with autopsy have been described. Within the scope of
      validation of cross-sectional radiology in forensic medicine, the comparison of
      findings of postmortem imaging and autopsy in chest trauma was performed.
      METHODS: This retrospective study includes 24 cases with chest trauma that
      underwent postmortem CT, MRI, and autopsy. Two board-certified radiologists,
      blind to the autopsy findings, evaluated the radiologic data independently. Each
      radiologist interpreted postmortem CT and MRI data together for every case. The
      comparison of the results of the radiologic assessment with the autopsy and a
      calculation of interobserver discrepancy was performed. RESULTS: Using combined
      CT and MRI, between 75% and 100% of the investigated findings, except for
      hemomediastinum (70%), diaphragmatic ruptures (50%; n=2) and heart injury (38%),
      were discovered. Although the sensitivity and specificity regarding
      pneumomediastinum, pneumopericardium, and pericardial effusion were not
      calculated, as these findings were not mentioned at the autopsy, these findings
      were clearly seen radiologically. The averaged interobserver concordance was 90%.
      CONCLUSION: The sensitivity and specificity of our results demonstrate that
      postmortem CT and MRI are useful diagnostic methods for assessing chest trauma in
      forensic medicine as a supplement to autopsy. Further radiologic-pathologic case
      studies are necessary to define the role of postmortem CT and MRI as a single
      examination modality.

PMID- 18347516
TI  - Left ventricular diverticulosis: demonstration on cardiac CT.
AB  - Cardiac computed tomography scanning is rapidly emerging as the noninvasive
      modality of choice for assessment of coronary artery disease. Secondary to the
      exquisite resolution of the modality, left ventricular diverticula can be well
      demonstrated. Left ventricular diverticula are rare, and in the past, the terms
      diverticula and aneurysm have been used interchangeably. The differentiation of
      diverticula and aneurysm is crucial for appropriate management. To the best of
      our knowledge, this is the first report of left ventricular diverticula seen on
      cardiac computed tomography examination.

PMID- 18347517
TI  - Left main coronary anomaly arising from the right sinus of Valsalva
      interarterial, septal, or a continuum?
AB  - Multidetector computed tomography angiography is increasingly used to visualize
      the coronary tree. It is emerging as the test of choice for the detection of
      anomalous coronary artery origin. It provides excellent spatial resolution and
      the ability to see the course of the coronary arteries and their proximity to
      adjacent structures. Invasive angiography has been the gold standard but does not
      allow the visualization of adjacent anatomic structures, which is crucial to
      correctly diagnosing the anomaly and determining the prognosis. We report a case
      of a 47-year-old woman with an anomalous left main coronary artery that arises
      from the right sinus of Valsalva where multidetector computed tomography
      angiography was key to the diagnosis and provided additional information that was
      not discernible from the invasive angiography.

PMID- 18347518
TI  - F-18 fluorodeoxyglucose PET/CT scanning in the diagnostic work-up of a primary
      pericardial mesothelioma: a case report.
AB  - Primary mesothelioma of the pericardium is a very rare malignancy. The antemortem
      diagnosis is difficult and requires a multidisciplinary approach. The use of F-18
      fluorodeoxyglucose-positron emission tomography/computed tomography whole body
      scan has been recently advocated to improve staging and to monitor treatment in
      pleural mesothelioma. This is the first case describing the use of F-18
      fluorodeoxyglucose-positron emission tomography/computed tomography in the
      diagnostic work-up of a primary pericardial mesothelioma.

PMID- 18347519
TI  - Organizing pneumonia as a manifestation of Pneumocystis jiroveci immune
      reconstitution syndrome in HIV-positive patients: report of 2 cases.
AB  - Organizing pneumonia (OP) is a nonspecific response to various forms of lung
      injury. Although patients with human immunodeficiency virus (HIV) infection tend
      to develop several respiratory disorders, especially infections and malignances,
      the association of HIV infection and OP is unusual. Pneumocystis jiroveci
      infection is also rarely associated with OP. We describe the radiologic findings
      in 2 HIV-positive patients who shortly after introduction of highly active
      antiretroviral therapy, presented with clinical and radiologic deterioration,
      despite elevation of the CD4 cell count and viral load decrease. In both
      patients, clinical and radiologic features were consistent with OP and lung
      biopsy revealed OP associated with P. jiroveci infection. These findings are
      consistent with immune reconstitution syndrome due to P. jiroveci.

PMID- 18347520
TI  - Usefulness of heavily T2-weighted magnetic resonance imaging in the diagnosis of
      alveolar lung metastases from pancreas mucinous adenocarcinoma.
AB  - We report the case of a patient with pancreatic adenocarcinoma and mucinous air
      space metastases, in which the diagnosis was suspected at magnetic resonance
      using heavily T2-weighted images obtained with magnetic resonance hydrographic
      sequences.

PMID- 18347521
TI  - Dendriform pulmonary ossification in a patient with a past history of giant cell
      tumor in femur.
AB  - Diffuse pulmonary ossification most commonly occurs in men in their fifth and
      sixth decades of life and is usually associated with diffuse and chronic lung
      disease, cardiac disease, or other systemic disorders. In this report, we
      describe a case of dendriform pulmonary ossification with a past history of giant
      cell tumor in the femur that occurred 8 years before. The nodules mimicked
      calcified pulmonary metastases. The patient was young (30 y old) and had no
      chronic lung or cardiac diseases. We speculate that the pulmonary ossification
      might have been due to dissemination of bone cells into the pulmonary circulation
      during bone curettage.

PMID- 18347522
TI  - Kaposi sarcoma after bilateral lung transplantation.
AB  - We describe radiologic findings in 2 patients and 18-fluoro-deoxy-glucose
      positron emission tomography/computed tomography findings in 1 patient who
      developed Kaposi sarcoma of the lung after bilateral lung transplantation. These
      findings included lung nodules, mediastinal or hilar lymphadenopathy, and pleural
      fluid.

PMID- 18347523
TI  - The empty azygos fissure: sign of an escaped azygos vein.
AB  - We present a case of displacement of the azygos vein from the azygos fissure
      secondary to deflation of the azygos lobe during surgery. We discuss the anatomy
      of the azygos fissure and possible mechanisms for formation of the "empty" azygos
      fissure and the "vanishing" azygos fissure.

PMID- 18347524
TI  - Diffuse alveolar hemorrhage after leflunomide therapy in a patient with
      rheumatoid arthritis.
AB  - We report the case of a young man, affected by rheumatoid arthritis who developed
      a rapid-onset short-of-breath, hemoptysis, and severe weakness, about 2 weeks
      after the administration of leflunomide. Chest radiography showed central
      bilateral opacities and pleural effusion as confirmed by the high-resolution
      computed tomography that demonstrated diffuse ground-glass and interlobular
      septal thickening as well. On admission at the Emergency Department, a
      microhematuria and a severe anemia were also documented. On the basis of the
      clinico-radiologic presentation, a pulmonary hemorrhage was likely to occur; so
      to clarify the origin of this process, a complete serologic examination was
      performed but all the antibodies were negative. Finally a renal biopsy was
      performed and it showed a pauci-immunologic glomerulonephritis and the
      bronchioloalveolar lavage confirmed the diffuse alveolar hemorrhage. In
      conclusion, the diagnosis of leflunomide-pulmonary-renal syndrome was rendered.
      The treatment with leflunomide was suspended; the conditions of the patient
      gradually improved and he became completely asymptomatic 1 week later.

PMID- 18347525
TI  - The third World Kidney Day: looking back and thinking forward.

PMID- 18347526
TI  - Looking into the crystal chip: can microarrays predict graft function?

PMID- 18347527
TI  - Nutritional status and behavior in subjects with type 1 diabetes, before and
      after islet transplantation.
AB  - BACKGROUND: To investigate whether changes of nutritional status and behavior are
      associated with islet transplantation (ITx) and to assess their possible
      mechanisms. METHODS: In this observational study, 52 subjects with type 1
      diabetes, 30 of whom received ITx, underwent nutritional assessments. The study
      consisted of questionnaires complemented by a dietary intake recording,
      anthropometric measurements, and body composition analysis. Laboratory tests were
      also reviewed as part of the follow up. RESULTS: After ITx, significant
      reductions in body weight (3.7 kg; P<0.0001), body mass index (1.39 kg/m2;
      P<0.0001), waist circumference (3.96 cm; P=0.006), and fat weight (3.28 kg;
      P<0.01) were observed. The average consumption of carbohydrate and protein were
      also lower than pretransplant, together with some micronutrients (vitamins B12
      and B6, zinc, and phosphorus). Insulin administration and changes in A1C were not
      associated with a significant change in anthropometric measurements. Subjects on
      exenatide after ITx showed significantly lower weight and body mass index than
      those not taking exenatide. CONCLUSIONS: ITx is associated with modifications in
      nutritional behavior and status. Drugs and health conditions are likely to be at
      least in part responsible for these changes, but a voluntary modification of
      eating habits by the patients also plays a role. Strict monitoring of nutritional
      parameters, counseling by experts in nutrition, and multivitamin/mineral
      supplement after ITx could be of benefit to the patients.

PMID- 18347528
TI  - Campath-1H induction therapy in African American and Hispanic first renal
      transplant recipients: 3-year actuarial follow-up.
AB  - BACKGROUND: In a retrospective study of the first 75 primary renal transplant
      patients given alemtuzumab induction at our center, 20 were African American
      (27%), 32 were Hispanic (43%), and 23 were non-African American, non-Hispanic
      (31%). METHODS: Alemtuzumab was given intraoperatively and 4 days later (0.3
      mg/kg), with planned low-dose maintenance mycophenolate mofetil (500 mg twice
      daily) and tacrolimus (targeted trough levels of 5 to 7 ng/ml) and no
      corticosteroid therapy after the first week. Median follow-up among ongoing
      survivors with a functioning graft was 45 months. RESULTS: Three-year actuarial
      patient and graft survival rates were 95% and 85% in African Americans, 89% and
      78% in Hispanics, and 96% and 96% in non-African Americans, non-Hispanics,
      respectively (not significant). Bioavailability of tacrolimus was significantly
      lower among African Americans in comparison with the other patient subgroups
      (P<or=.002). While the incidence of biopsy-proven acute rejection was 20% (4/20)
      in African Americans, 19% (6/32) in Hispanics, and 13% (3/23) in non-African
      American, non-Hispanic (not significant), chronic allograft dysfunction occurred
      more frequently among African Americans (10/20) in comparison with Hispanics
      (8/32) and non-African American, non-Hispanics (8/23) (P=0.08, log-rank test). In
      addition, there was a trend at 6 and 12 months posttransplant for the mean serum
      creatinine to be less favorable among African American patients (P=0.08 and
      0.07). No group had increased infection or malignancy. CONCLUSIONS: This
      immunosuppressive protocol appears reasonably safe for 3 years after renal
      transplantation but suggests higher incidences of biopsy-proven acute rejection,
      chronic allograft dysfunction, and borderline poorer renal function among African
      Americans in comparison with the other patient subgroups.

PMID- 18347529
TI  - Pancreas-kidney transplantations with primary bladder drainage followed by
      enteric conversion: graft survival and outcomes.
AB  - BACKGROUND: In the Leiden University Medical Centre, a two-step approach is
      routinely used in simultaneous pancreas-kidney (SPK) transplantations: primary
      bladder drainage (BD) followed by elective enteric conversion. The rationale for
      this approach is to prevent the short-term disadvantages of primary enteric
      drainage (intra-abdominal abscesses, pancreas graft loss) and the long-term
      urological complications related to bladder drainage. Aim of the present study is
      to evaluate survival and (urological) complications of this approach compared to
      enteric drainage (ED). METHODS: Patient records of all 98 SPK transplantations in
      the period 1997-2004 were reviewed for complications during the initial
      hospitalization until 30 days after discharge, and to assess urological
      complications and graft survival until the last hospital visit. Median duration
      of follow-up was 4.3 years for pancreas graft survival, 4.7 years for kidney
      graft survival, and 4.8 years for patient survival. RESULTS: Patient survival was
      significantly better in BD patients than in ED patients (chi2=9.89 P<0.01).
      Pancreas graft survival was also better in BD patients after adjustment for the
      longer pancreas warm ischemia time in BD patients (P=0.05). The survival rates in
      our patient population seem higher than reported by the International Pancreas
      Transplant Registry, particularly in BD patients. Urological complications
      occurred in nine BD patients (10.3%), comparable to the rates reported for
      enteric-drained grafts. CONCLUSIONS: This two-step approach of SPK
      transplantation results in excellent survival rates, with urological complication
      rates comparable to those reported for enteric-drained grafts, and may thus be
      viewed as a safe and effective procedure of SPK transplantation.

PMID- 18347530
TI  - Indications for and outcomes after combined lung and liver transplantation: a
      single-center experience on 13 consecutive cases.
AB  - BACKGROUND: Combined lung and liver transplantation (Lu-LTx) is a therapeutic
      option for selected patients with coexisting lung and liver disease. For several
      reasons, Lu-LTx is performed in few centers and information about the technical
      issues, posttransplant management and long-term outcomes associated with this
      procedure is limited. METHODS: We analyzed data from 13 consecutive patients who
      underwent combined Lu-LTx at Hannover Medical School (Hannover, Germany) between
      April 1999 and December 2003. The main indications were cystic fibrosis, alpha1
      proteinase inhibitor deficiency and portopulmonary hypertension. All patients had
      advanced cirrhosis and severe pulmonary disease manifestation. RESULTS: Ten
      patients received a sequential double Lu-LTx, one patient received a single Lu
      LTx, one received a double lung and split liver transplantation, and one received
      an en-bloc heart-lung and liver transplantation. Immunosuppression was based on
      cyclosporine in a triple/quadruple regimen. Postoperative surgical complications
      occurred in eight patients. There were two perioperative deaths; two patients
      died during the first year on day 67 and 354, respectively, and one patient died
      at month 53. The overall patient survival rates at 1, 3, and 5 years were 69%,
      62%, and 49%, respectively. CONCLUSION: Combined Lu-LTx is a therapeutic option
      for highly selected patients with end-stage lung and liver disease with
      acceptable long-term outcome.

PMID- 18347531
TI  - Cost-effectiveness of colorectal cancer screening in renal transplant recipients.
AB  - BACKGROUND: Colorectal cancer screening is now standard practice in most
      developed countries. The aim of this study was to determine the cost
      effectiveness of colorectal cancer screening, with annual fecal occult blood
      testing, in renal transplant recipients. METHOD: A Markov model was developed to
      compare the effects of annual fecal occult blood testing (FOBT) as screening for
      colorectal cancer in a cohort of renal transplant recipients ages 50-70 years,
      versus no screening. Data on cancer risk and survival were obtained from the
      ANZDATA Registry. Accuracy of FOBT, cancer stage distribution of the screened and
      unscreened arms, and adverse effects of colonoscopy were extrapolated from
      general population data because of unavailability of equivalent data in renal
      transplant recipients. RESULTS: When the participation rate was 50%, the average
      cost for annual FOBT was $5076. The estimated incremental cost-effectiveness
      ratio was $22,309 per life year saved. Using a series of sensitivity analyses,
      the choice of screening strategy was most sensitive to the prevalence of disease,
      test specificities, and participation rate. When the base-case analyses were
      tested over the worst and best-case scenarios, the incremental cost-effectiveness
      ratio varied from $32,863 to $95,668 per life year saved. CONCLUSION: Under the
      most favorable conditions, immunochemical FOBT screening in renal transplant
      recipients appears good value for money. Uncertainties, however, exist in the
      model's influential estimates. Primary research into these uncertainties is
      necessary to confirm whether population colorectal cancer screening is cost
      effective in renal transplant population.

PMID- 18347532
TI  - Urinary C4d does not correlate with C4d-staining in peritubular capillaries but
      reflects nonspecific glomerular injury.
AB  - BACKGROUND: C4d-staining in peritubular capillaries (PTC) in allograft biopsies
      is a hallmark of antibody-mediated rejection (AMR). This study investigated
      whether urinary C4d correlates with C4d-staining in PTC, allowing for a
      noninvasive screening procedure. METHODS: Urine samples from 34 patients with
      diffuse C4d-staining in PTC (C4d-pos group) and 68 urine samples from patients
      with negative C4d-staining in PTC (C4d-negative group) matched 1:2 according to
      proteinuria and time posttransplant were compared regarding urinary C4d-levels.
      RESULTS: Overall, urinary C4d/creatinine-ratios (C4d/C) were not different
      between the C4d-positive and the C4d-negative group (P=0.55). Urinary C4d/C
      strongly correlated with total protein/creatinine-ratios (P/C) (r2=0.53;
      P<0.0001) and albumin/creatinine-ratios (r2=0.52; P<0.0001). C4d/C were not
      different between C4d-pos and C4d-negative patients with P/C>50 mg/mmol (P=0.57)
      and P/C<50 mg/mmol (P=0.65), respectively. However, in both the C4d-positive and
      the C4d-negative group urinary C4d/C were significantly higher in patients with
      P/C>50 mg/mmol than in patients with P/C<50 mg/mmol (P<or=0.005). Furthermore,
      longitudinal analysis in 3 patients with distinct clinico-pathological courses
      demonstrated that urinary C4d/C closely followed P/C regardless of C4d-staining
      in PTC. CONCLUSION: Urinary C4d does not correlate with C4d-staining in PTC but
      reflects nonspecific glomerular injury. Therefore, urinary C4d is likely not a
      useful biomarker for non-invasive screening and monitoring of AMR.

PMID- 18347533
TI  - Minimal acute cellular rejection remains prevalent up to 2 years after lung
      transplantation: a retrospective analysis of 2697 transbronchial biopsies.
AB  - BACKGROUND: Acute cellular rejection (ACR) is the most consistently reported risk
      factor for the development of bronchiolitis obliterans syndrome, an important
      cause of late mortality after lung transplantation. This retrospective study
      comprised all transbronchial biopsies (TBB) obtained during the first 2 years
      after transplantation in a consecutive cohort of 299 patients transplanted 1996
      2006 (n=2697). METHODS: TBB were aligned to the closest TBB surveillance
      schedule. RESULTS: Patients completed a mean of 6+/-2 (median 8) TBB schedules.
      The proportion of patients demonstrating ACR (>or=A2) decreased with increasing
      time from transplantation from 43% at 2 weeks to 27% at 6 months, and 13% and 4%
      at 1 and 2 years, respectively (trend test, P<0.0001). There was a significant
      trend between increased previous occurrence of ACR and increasing subsequent risk
      of A>or=2 from 1, 3, and 12 months after transplantation (P<0.0001, P=0.0005, and
      P=0.001, respectively). Multivariate analyses identified interleukin-2-receptor
      induction with daclizumab versus antithymocyte globulin was independently
      associated with more frequent/severe ACR (P<0.0001). CONCLUSIONS: Minimal ACR
      remains prevalent up to 2 years after lung transplantation. Previous occurrence
      of ACR was associated with an increased risk of subsequent ACR.

PMID- 18347534
TI  - Pharmacokinetics of tacrolimus in living donor liver transplant and deceased
      donor liver transplant recipients.
AB  - INTRODUCTION: Hepatic dysfunction is an important determinant of the clearance of
      tacrolimus; however, the impact of reduced hepatic mass in living donor liver
      transplant (LDLT) patients on the drug exposure and clearance of tacrolimus is
      not known. AIM.: The aim of the present study is to compare the dosage,
      concentration and pharmacokinetics parameters of tacrolimus between LDLT and
      deceased donor liver transplant (DDLT) recipients. PATIENTS AND METHODS: Daily
      doses used and trough concentrations measured were compared in 12 LDLT and 12
      DDLT patients. Multiple blood samples were taken over one dosing interval after
      oral tacrolimus administration, and pharmacokinetics differences were compared.
      RESULTS: The mean tacrolimus dosage in first 14 postoperative days was (0.06
      mg/kg/day) for LDLT and (0.09 mg/kg/day) for DDLT (P=0.0001). Despite the lower
      doses used, mean trough concentration was significantly greater in LDLT as
      compared with DDLT (8.8+/-2.5 ng/mL vs. 6.79+/-1.5 ng/mL, respectively, P=0.013).
      On the day of the pharmacokinetic study, minimum Concentration (Cmin), 12-hr
      postdose concentration (Clast), and average concentration (Cavg) were
      significantly greater in LDLT as compared with DDLT (LDLT: 6.6+/-2.4 ng/mL, 7.2+/
      1.8 ng/mL, 8.9+/-3.0 ng/mL; DDLT: 4.3+/-1.0 ng/mL, 4.9+/-1.6 ng/mL, 5.9+/-1.4
      ng/mL, P=0.02, 0.04, and 0.02, respectively). Dose normalized AUC was 37.7%
      greater and clearance, 47.5% lower in LDLT as compared with DDLT. CONCLUSION:
      Although not statistically significant, the dose normalized AUC was 37.7% greater
      and clearance 47.5% lower in LDLT as compared with DDLT. An initial tacrolimus
      dose reduction of about 30-40% may be prudent in LDLT compared with DDLT
      recipients.

PMID- 18347535
TI  - Minimizing morbidity of organ donation: analysis of factors for perioperative
      complications after living-donor nephrectomy in the United States.
AB  - BACKGROUND: Expansion of living kidney donation through liberalizing acceptance
      criteria invites a renewed focus on safety and outcomes. Wide variability exists
      in reported donor complications, and associated risk factors are ill defined. Use
      of administrative data can overcome the bias of single-center studies and
      identify variables associated with untoward events. METHODS: The study population
      consisted of 3074 living kidney donors from 28 centers during 2004 and 2005. Data
      from a large healthcare registry were used to retrospectively identify the study
      cohort. Perioperative complications were identified using ICD-9-CM coding and
      classified according to the Clavien system. Logistic regression models were
      constructed to identify donor and center factors associated with complications.
      RESULTS: There were no perioperative deaths. The overall complication rate was
      10.6% and major complications defined by Clavien grade >or=3 was 4.2%. The
      prevalence of tobacco use, obesity, and hypertension, was 7.8%, 2.4%, and 2.3%,
      respectively. Age >50 (odds ratio [OR]=1.81, 95% confidence interval [95%
      CI]=1.25-2.61), tobacco use (OR=1.41, 95% CI=1.02-1.94), obesity (OR=1.92, 95%
      CI=1.06-3.46), and annual center volume <or=50 (OR=2.28, 95% CI=1.68-3.09), were
      significantly associated with overall morbidity, however only annual center
      volume <or=50 (OR=2.07, 95% CI=1.27-3.37) was significantly associated with a
      risk of major complications. CONCLUSIONS: The inclusion of donors with tobacco
      abuse, obesity, and age >50 increases complications; however, the risk of major
      morbidity is small. Use of administrative data represents an important tool to
      facilitate the reconciliation of an increased need for organ donors with the
      concern for donor safety.

PMID- 18347536
TI  - Human myoblast engraftment is improved in laminin-enriched microenvironment.
AB  - BACKGROUND: One major challenge in developing cell therapy for muscle diseases is
      to define the best condition for the recipient's muscle to niche donor cells. We
      have examined the efficiency of human myoblast transplantation in an
      immunodeficient animal model, after local irradiation, as well as the potential
      impact of laminin on myoblast behavior. METHODS: Human myoblasts were injected
      into preirradiated tibialis anterior muscles from immunodeficient mice. The donor
      cell engraftment, proliferation, and laminin content within the transplanted
      muscles were evaluated by immunocytochemistry. Additionally, the effect of
      laminin upon myoblast proliferation, migration, and survival was ascertained in
      vitro. RESULTS: Engraftment of human myoblasts into the skeletal muscle of
      immunodeficient Rag2-/gammac-/C5- mice presubjected to local irradiation provided
      the best niche for myoblast engraftment, as demonstrated by the number of viable
      and proliferating donor cells found in the host muscle. Local irradiation
      significantly enhanced laminin deposition within the recipient's muscle and donor
      cells were preferentially located in laminin-enriched areas. The same batch of
      myoblasts used for in vivo injections also responded to laminin in vitro with
      increased proliferation and cell survival, as well as an improved migratory
      response. CONCLUSIONS: We show that local irradiation enhances the laminin
      content in the host muscle microenvironment and provides a better engraftment of
      human myoblasts. In addition, laminin increases myoblast proliferation, survival,
      and migration in vitro. These data provide combined in vivo and in vitro evidence
      that laminin status should be taken into account when designing experimental and
      clinical cell therapy strategies for muscle disease.

PMID- 18347537
TI  - Carbon monoxide protects against ischemia-reperfusion injury in an experimental
      model of controlled nonheartbeating donor kidney.
AB  - BACKGROUND: CO-releasing molecule-3 (CORM-3) is a transitional metal carbonyl
      that liberates carbon monoxide under appropriate conditions. Carbon monoxide
      exerts effects on intracellular apoptotic and inflammatory pathways, which
      suggest a role in reducing the effects of renal ischemia/reperfusion (I/R)
      injury. This study investigated the effects of CORM-3 administered at the time of
      reperfusion in a model of controlled nonheartbeating donor kidneys. METHODS:
      Porcine kidneys (n=4) were subjected to 10 min warm ischemia and 18 hr cold
      storage (CS) and then treated as follows: CORM-3 (50, 100, 200, and 400 microM
      doses), iCORM-3 (inactive carbon monoxide-releasing molecule, 50 microM), and
      control (no further intervention). Renal hemodynamics and function were then
      measured during 3-hr reperfusion with autologous blood using an isolated organ
      perfusion system. RESULTS: CORM-3 at a concentration of 50 microM improved renal
      blood flow (RBF) compared with the iCORM and control groups (area under the curve
      774+/-19 vs. 448+/-88 vs. 325+/-70, respectively, P=0.002). CO-releasing molecule
      3 at a concentration of 50 microM also improved renal function during reperfusion
      with a greater area under the curve for creatinine clearance (CORM-3: 14+/-6 vs.
      iCORM: 3.3+/-0.1 vs. control: 2.2+/-2 mL/min, P=0.006) and higher urine output
      (CORM-3: 793+/-212 vs. iCORM: 368+/-72 vs. control: 302+/-211 mL, P=0.01). CO
      releasing molecule-3 at a concentration of 100 microM exerted similar effects.
      Treatment with CORM-3 at higher doses (200 and 400 microM) led to poor renal
      hemodynamics and function after reperfusion. CONCLUSION: Low-dose CORM-3
      significantly ameliorates the effects of ischemia/reperfusion in a porcine model
      of controlled nonheartbeating donor kidney transplantation.

PMID- 18347538
TI  - Dichotomous effects of rosiglitazone in transplantation-induced systemic
      vasodilator dysfunction in rats.
AB  - BACKGROUND: Transplantation-induced systemic endothelial dysfunction causes
      severe cardiovascular morbidity and mortality after transplantation.
      Interventions that improve systemic endothelial function after transplantation
      and furthermore reduce intragraft vascular dysfunction might improve graft and
      patient survival. Treatment with the PPARgamma agonist rosiglitazone is an
      intervention that potentially fulfills these criteria. In this study, we
      determined the effect of rosiglitazone treatment on transplantation-induced
      endothelial dysfunction and vasomotor activity in an experimental model for
      chronic transplant dysfunction in rats. METHODS: Lewis abdominal aortic
      allografts were orthotopically transplanted into Brown Norway recipients that
      received either regular chow or chow containing rosiglitazone (approximately 4.2
      mg/day). Endothelium-dependent (response to metacholine) and total (response to
      sodium nitrite) vasodilatory responses were determined in autologous thoracic
      aortic rings using an ex vivo organ bath setup. Measurements were performed 8
      weeks after transplantation. RESULTS: Aortic allografting induced systemic
      endothelial dysfunction as measured by reduced endothelium-dependent vasodilation
      in the recipient's vascular system. Rosiglitazone treatment restored endothelium
      dependent vasodilatory responses to pretransplantation levels. However,
      rosiglitazone treatment reduced the total dilatory response despite normalized
      endothelial function, indicating impairment of vascular smooth muscle cell
      vasomotor activity. CONCLUSIONS: Rosiglitazone treatment after allogeneic
      transplantation restores endothelial function but impairs vascular smooth muscle
      cell vasomotor activity. This dichotomous effect of rosiglitazone might impede
      use of rosiglitazone after organ transplantation since this potentially increases
      cardiovascular risk despite improved endothelial cell function.

PMID- 18347539
TI  - Heparin-bound transforming growth factor-beta3 enhances neocartilage formation by
      rabbit mesenchymal stem cells.
AB  - BACKGROUND: Heparin binds growth factors to form a stable complex that maintains
      the biological activity and can retard the release pattern. To differentiate the
      embedded the stem cells, heparin-bind transforming growth factor (TGF)-beta3 was
      mixed with rabbit mesenchymal stem cells encapsulated with thermo-reversible
      hydrogel. It is suggested that the heparin-bound TGF-beta3 would help to increase
      the chondrogenic differentiation of rabbit mesenchymal stem cells in thermo
      reversible hydrogel. METHODS: To determine the optimal condition for neocartilage
      formation, we characterized hydrogel constructs with growth factor release
      profiles, confocal laser microscopy, reverse transcription-polymerase chain
      reaction analysis, and histology. RESULTS: Reverse transcription-polymerase chain
      reaction analysis of the resultant cartilage tissue revealed that a thermo
      reversible hydrogels with a heparin-bound TGF-beta3 was optimal for cartilage
      tissue formation as measured by production of collagen Type II, aggrecan, and
      SOX9, and cartilage oligomeric matrix protein gene expression. Additionally, the
      proliferation rate and cartilage specific ECM production were both significantly
      greater in the presence of heparin-bound TGF-beta3 than in the control. The
      amount of cartilage-associated ECM proteins was examined by immunohistochemical
      staining (collagen type II), Safranin-O staining, and Alcian blue staining.
      CONCLUSIONS: These data indicate the potential use of heparin-binding TGFbeta-3
      for reconstruction of neocartilage formation.

PMID- 18347540
TI  - Hemodynamic resuscitation with arginine vasopressin reduces lung injury after
      brain death in the transplant donor.
AB  - BACKGROUND: The autonomic storm accompanying brain death leads to neurogenic
      pulmonary edema and triggers development of systemic and pulmonary inflammatory
      responses. Neurogenic vasoplegia exacerbates the pulmonary injury caused by brain
      death and primes the lung for ischemia reperfusion injury and primary graft
      dysfunction in the recipient. Donor resuscitation with norepinephrine ameliorates
      the inflammatory response to brain death, however norepinephrine has deleterious
      effects, particularly on the heart. We tested the hypothesis that arginine
      vasopressin is a suitable alternative to norepinephrine in managing the
      hypotensive brain dead donor. METHODS: Brain death was induced in Wistar rats by
      intracranial balloon inflation. Pulmonary capillary leak was estimated using
      radioiodinated albumin. Development of pulmonary edema was assessed by
      measurement of wet and dry lung weights. Cell surface expression of CD11b/CD18 by
      neutrophils was determined using flow cytometry. Enzyme-linked immunosorbent
      assays were used to measure the levels of TNFalpha, IL-1beta, CINC-1, and CINC-3
      in serum and bronchoalveolar lavage. Quantitative reverse-transcription
      polymerase chain reaction was used to determine the expression of cytokine mRNA
      (IL-1beta, CINC-1 and CINC-3) in lung tissue. RESULTS: There was a significant
      increase in pulmonary capillary permeability, wet/dry lung weight ratios,
      neutrophil integrin expression and pro-inflammatory cytokines in serum (TNFalpha,
      IL-1beta, CINC-1 and CINC-3), bronchoalveolar lavage (TNFalpha and IL-1beta) and
      lung tissue (IL-1beta and CINC-1) in braindead animals compared to controls.
      Correction of neurogenic hypotension with either arginine vasopressin or
      norepinephrine limits edema, reduces pulmonary capillary leak, and modulates
      systemic and pulmonary inflammatory responses to brain death. CONCLUSIONS:
      Arginine vasopressin and norepinephrine are equally effective in treating the
      hypotensive pulmonary donor in this rodent model.

PMID- 18347541
TI  - Simultaneous protection against allograft rejection and graft-versus-host disease
      after total lymphoid irradiation: role of natural killer T cells.
AB  - BACKGROUND: The use of combined organ and bone marrow transplantation has been
      studied extensively in rodent models to induce immune tolerance to organ grafts.
      However, bone marrow transplants with mature donor T cells can induce graft
      versus-host disease even in human leukocyte antigen-matched humans. We determined
      whether total lymphoid irradiation can simultaneously protect against graft
      versus-host disease while facilitating tolerance. METHODS: To more closely model
      clinical studies, we added mature donor T cells to bone marrow grafts combined
      with heart grafts, and compared murine graft and host survival after conditioning
      with nonmyeloablative total body or total lymphoid irradiation and depletive anti
      T-cell antibodies. RESULTS: Conditioning with total lymphoid irradiation
      protected hosts against both graft-versus-host disease and organ graft rejection.
      Although nonmyeloblative total body irradiation prevented organ graft rejection,
      all hosts succumbed to lethal graft-versus host disease. Induction of tolerance
      with total lymphoid irradiation and anti-T-cell antibodies was dependent on the
      presence of regulatory host natural killer T cells, and expression of CD1d on
      donor marrow but not heart graft cells. CONCLUSION: Conditioning with total
      lymphoid irradiation and anti-T-cell antibodies prevented host-versus-donor and
      donor-versus-host alloimmune responses. Tolerance required host natural killer T
      cell recognition of CD1d on donor marrow cells.

PMID- 18347542
TI  - Effect of CXCL-1/KC production in high risk vascularized corneal allografts on T
      cell recruitment and graft rejection.
AB  - BACKGROUND: The survival rate of corneal allografts in high-risk vascularized
      corneal bed recipients is poor, similar to vascularized solid organ allografts.
      Although the early induction of selective chemokines in solid organs is required
      for the optimal recruitment of T cells into rejecting allografts, little is known
      about the role of these chemokines in high risk corneal allografts. METHODS:
      Orthotopic corneal allotransplants were performed in low-risk (nonvascularized)
      and high-risk (vascularized) C57BL/6 (H-2b) recipients using Balb/c (H-2d)
      donors. Intragraft production of CXC chemokines was measured by Luminex and
      enzyme-linked immunosorbent assay on corneal transplant extracts at different
      times after surgery. Rabbit anti-KC serum was used to test its role in high risk
      corneal allograft survival. RESULTS: Early upregulation of CXCL1/KC occurs 3 days
      after transplantation in high risk allograft only. Moreover, the T-cell
      chemoattractants, CXCL9/Mig and CXCL10/IP10, are produced late (day 10) after
      surgery and their production correlates with the recruitment of CD4 T cells into
      the graft. Furthermore, in vivo neutralization of CXCL1/KC with anti-KC sera
      results in increased graft survival and decreased recruitment of T cells into
      high-risk allografts. CONCLUSION: We propose that a high risk vascularized cornea
      behaves like a vascularized solid organ transplant. The early production of
      CXCL1/KC is crucial to the induction of T-cell chemoattractants necessary for the
      recruitment of allospecific CD4 T cells into the graft. In vivo neutralization of
      CXCL1/KC represents a potential novel therapy that could be used to increase the
      survival rate of high-risk vascularized corneal allografts.

PMID- 18347543
TI  - Gene expression patterns in deceased donor kidneys developing delayed graft
      function after kidney transplantation.
AB  - BACKGROUND: Delayed graft function (DGF) after kidney transplantation (KTx)
      ranges between 2% and 50%. The mechanisms leading to DGF deserve special interest
      because DGF exerts negative influences on long-term outcomes. We studied gene
      expression profiles in deceased donor kidney (DDK) biopsies with and without DGF.
      METHODS: Gene expression profiling was performed on donor kidney tissues from 33
      DDK with the use of microarrays. DDK were classified as grafts with immediate
      function (non-DGF; n=21) and grafts with DGF (n=12). DGF was defined as a
      dialysis requirement in the first week after transplantation. Demographic donor
      and recipient information was collected. The robust-multiarray average method was
      used to estimate probe set expression summaries. Logistic regression was used to
      identify genes significantly associated with DGF development. RESULTS: Patients
      were followed for 3 months after KTx. Thirty-eight probe sets (n=36 genes) were
      univariably differentially expressed in DDK with DGF when compared with DDK with
      non-DGF (alpha=0.001). Sixty-nine probe sets (n=65 genes) were differentially
      expressed in DDK with DGF when compared with DDK with non-DGF after adjusting for
      cold ischemia time (alpha=0.001). Gene ontology terms classified the
      overexpressed genes in DDK with DGF as principally related to cell cycle/growth
      (e.g., IGFBP5, CSNK2A2), signal transduction (e.g., RASGRP3), immune response
      (e.g., CD83, BCL3, MX1), and metabolism (e.g., ENPP4, GBA3). TNFRSF1B was
      overexpressed in DDK with DGF. CONCLUSIONS: Cold ischemia time was a predictor of
      DGF independently of the preservation method. We identified a set of 36 genes
      candidates of DGF in DDK, with genes involved in the inflammatory response being
      the more important.

PMID- 18347544
TI  - Poor tolerance of sirolimus in a steroid avoidance regimen for renal
      transplantation.
AB  - Vascular disease and chronic allograft nephropathy have prompted re-evaluation of
      steroids and calcineurin inhibitors (CNIs) in renal transplantation. Sirolimus
      (SRL) can facilitate early CNI withdrawal. We report on the Early CNI and Steroid
      Elimination in Leeds (ECSEL) study, which was terminated early due to poor
      tolerability of SRL. Basiliximab/methylprednisolone induction was used, then 2
      months of tacrolimus (TAC) and mycophenolate mofetil (MMF) treatment. A total of
      51 patients were randomized to continue TAC/MMF or switch to SRL/MMF. In ECSEL1,
      patients were switched at 2 months (n=10). In ECSEL2, SRL was introduced at
      months 4-6 and TAC was tapered (n=13). Median overall follow up was 701 days. All
      10 ECSEL1 and 10 of 13 (77%) ECSEL2 patients discontinued SRL due to adverse
      events, including leucopenia, rash, mucosal ulceration, arthralgia, and possible
      pneumonitis. Mean end-of-study creatinine was comparable in all groups. Sirolimus
      should be used with caution in complete CNI and steroid withdrawal, due to the
      resultant intolerable adverse event profile.

PMID- 18347545
TI  - Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient
      mice depends on the thymus transplant technique.
AB  - Xenothymus transplantation under the kidney capsule in athymic rodents frequently
      leads to multiorgan autoimmunity. Herein, we explore whether this is an intrinsic
      risk of xenothymus grafting or whether it depends on the transplant technique. We
      developed a new technique of "venous pouch" thymus grafting (heart-xenothymus)
      and compared this with the conventional kidney subcapsular technique (kidney
      xenothymus) in a rat-into-nude-mouse model. Whereas lethal autoimmunity developed
      in 90% of kidney-xenothymus recipients, all heart-xenothymus grafted mice
      remained completely healthy. Autoimmunity in heart-xenothymus recipients was
      absent despite a significantly improved T-cell generation and was associated with
      significantly higher CD4+CD25+ T-cell frequencies and CD4+CD25+ cell Foxp3 mRNA
      levels than those observed in kidney-xenothymus recipients. In conclusion, we
      describe a novel vascular pouch technique of xenothymus transplantation that
      prevents the development of autoimmunity in nude mice. Our data further suggest
      that prevention of autoimmunity is related to a superior development of
      regulatory T-cells.

PMID- 18347546
TI  - Pericardial effusion coincident with sirolimus therapy: a review of Wyeth's
      safety database.
AB  - Sirolimus is an immunosuppressive agent approved for prophylaxis of acute
      rejection in renal transplant patients aged 13 years or older. A retrospective
      review of pericardial effusion coincident with sirolimus therapy was conducted
      from key clinical trials and spontaneous reporting sources. A significantly
      higher rate of pericardial effusion occurred with sirolimus versus azathioprine
      treatment in a cardiac transplantation trial (28.6% versus 9.3%, respectively).
      Cases of pericardial effusion were also observed in the sirolimus treatment arms
      of three de novo renal transplant studies (rates 0.5 to 1.9%). Although most of
      the pericardial effusions occurred in cardiac transplantation, sirolimus is not
      approved for this use. As of January 31, 2007, the Wyeth safety database (which
      includes clinical trial data and spontaneous reports) contained reports of
      pericardial effusion in 56 sirolimus-treated patients, 31 of whom required
      pericardial drainage. These data suggest that pericardial effusion should be
      considered in the differential diagnosis of a clinical deterioration in
      posttransplant patients treated with sirolimus. The adverse reaction of
      pericardial effusion has been added to product labeling.

PMID- 18347547
TI  - Prolonged islet allograft survival in diabetic mice upon macrophage depletion by
      clodronate-loaded erythrocytes.
AB  - Early impairment of islet function and graft loss strongly limit the success of
      allogenic islet transplantation in insulin-dependent diabetes. Macrophages play a
      key role in this process thus the depletion of these cells may strongly affect
      islet survival. In this study, we have evaluated the effect of the depletion of
      macrophages in mouse allograft rejection using a new approach based on a single
      infusion of red blood cells loaded with the synthetic analogue of pyrophosphate
      clodronate. Graft survival was 19.4+/-0.89 and 20+/-2 days in the two control
      groups treated with physiological solution and unloaded erythrocytes,
      respectively; 25+/-1.9 days in the group treated with free-clodronate and 35+/-6
      days in the erythrocytes-loaded group. Our results indicate clodronate
      selectively targeted to the macrophagic cells by a single administration of
      engineered erythrocytes can significantly prolong islet graft survival and open
      new therapeutic strategies in islet transplantation.

PMID- 18347548
TI  - The use of Dacron graft for cavo-cavostomy in orthotopic liver transplantation.
AB  - The end-to-end "interposition" technique and end-to-side "piggyback" technique
      are standard approaches to in situ anastomosis during orthotopic liver
      transplantation. We demonstrate that anastomosis of liver allograft to a Dacron
      vena cava graft can be a feasible solution if traditional anastomoses cannot be
      used. A 55-year-old man with end-stage liver failure from alcoholic cirrhosis
      underwent orthotopic liver transplantation; however, an intraoperative
      complication during recipient hepatectomy rendered the native vena cava
      unsalvageable. In addition, the donor vena cava was too short to bridge the caval
      defect for interposition. We therefore used Dacron for an in situ graft to span
      the gap, with subsequent anastomosis of the allograft to the prosthetic graft in
      piggyback fashion. The patient did well postoperatively; his only major
      complication was late anastomotic stenosis, which was treated successfully with
      balloon dilatation. Unfortunately the patient became recidivous and expired ten
      months posttransplant, despite indications of satisfactory allograft function.

PMID- 18347549
TI  - Tongue transplantation: 10-month follow-up.

PMID- 18347550
TI  - Diarrhea in a renal allograft recipient in the tropics.

PMID- 18347551
TI  - Ureteral stent placement and BK virus allograft nephropathy in renal transplant
      recipients.

PMID- 18347552
TI  - Survey of the use of nonheart-beating kidneys in pediatric practice in the United
      kingdom.

PMID- 18347554
TI  - Diets, drugs and surgery for weight loss.

PMID- 18347555
TI  - The myeloma landscape in 2008.
AB  - Highlights From the American Society of Hematology 2007 Annual Meeting, Atlanta,
      Georgia, December 8-11, 2007.

PMID- 18347556
TI  - Incorporating the Oncotype DX breast cancer assay into community practice: an
      expert Q&A and case study sampling.
AB  - Advances in breast cancer research have confirmed that this malignancy is not a
      single disease, but rather a collection of genetically distinct diseases with
      different treatment requirements. In recent years, several studies have confirmed
      the clinical validity of the Oncotype DX breast cancer assay, not only as a way
      to predict recurrence but also as a tool for determining therapeutic benefit from
      adjuvant chemotherapy. Recently, Drs. Terry Mamounas, G. Thomas Budd, and Kathy
      Miller answered questions about the Oncotype DX assay that are particularly
      relevant to routine clinical practice. This expert dialog provides a useful
      update and essential clinical insights about how, why, and when community
      oncologists may want to incorporate this multi-gene assay into their care of
      breast cancer patients. In addition, sample case studies offer tangible examples
      of the practical application of Oncotype DX.

PMID- 18347557
TI  - Recent advances in the treatment of lymphoma.
AB  - A Review of Selected Presentations From the 49th American Society of Hematology
      Annual Meeting and Exposition, December 8-11, 2007, Atlanta, Georgia.

PMID- 18347558
TI  - New drugs for ovarian cancer.

PMID- 18347559
TI  - Advances in HER2-positive breast cancer.

PMID- 18347560
TI  - Controversies regarding the use of dexamethasone in patients with multiple
      myeloma.

PMID- 18347561
TI  - Inherited and acquired hematologic disorders in athletes.

PMID- 18347562
TI  - Response in acute myeloid leukemia.
AB  - For many years, response to induction therapy in acute myeloid leukemia was
      classified as "complete response" (CR) or "no CR." The emphasis on CR reflected
      the proven ability of CR to extend survival, the outcome of primary interest to
      patients. Beginning with the adoption of complete response with incomplete
      platelet recovery (CRp), recent years have seen the acceptance of responses less
      than CR as beneficial. Although these responses denote that a drug is active,
      relatively little attention has been paid to the effect of such responses on
      survival. This article explores the effect of such responses on survival.

PMID- 18347563
TI  - Second-line chemotherapy for advanced hormone-refractory prostate cancer.
AB  - Prostate cancer is the most common cancer occurring among men in the United
      States. In spite of the disease's favorable prognosis, approximately 30,000 U.S.
      men develop incurable metastatic disease each year, making prostate cancer the
      second-leading cause of cancer-related deaths among men in the United States.
      Although hormone-based therapies generally result in rapid responses, virtually
      all patients ultimately develop androgen-independent progressive disease. It is
      among these men with hormone-refractory prostate cancer (HRPC) that the role of
      chemotherapy continues to be investigated. To date, three drugs (estramustine,
      mitoxantrone, and docetaxel) have been approved by the US Food and Drug
      Administration (FDA) for first-line chemotherapy in HRPC, with other agents and
      combinations now under evaluation in ongoing clinical trials. Patients whose
      tumors progress through first-line chemotherapy have limited treatment options
      available to them and less than half of all men with HRPC will receive any second
      line chemotherapy. To date, only one phase III randomized clinical trial has been
      completed in this setting and no therapies are FDA-approved. We review here the
      entirety of phase II and III data evaluating chemotherapy agents in second-line
      HRPC.

PMID- 18347564
TI  - Acute myocardial infarction: an unusual presentation of essential thrombocytosis
      in a 17-year-old man.

PMID- 18347565
TI  - Review: challenges in the management of thrombocytosis in young patients.

PMID- 18347566
TI  - Reduction of quaternary ammonium-induced ocular surface toxicity by emulsions: an
      in vivo study in rabbits.
AB  - PURPOSE: To evaluate and compare the toxicological profiles of two quaternary
      ammonium compounds (QAC), benzalkonium chloride (BAK), and cetalkonium chloride
      (CKC), in standard solution or cationic emulsion formulations in rabbit eyes
      using newly developed in vivo and ex vivo experimental approaches. METHODS:
      Seventy eyes of 35 adult male New Zealand albino rabbits were used in this study.
      They were randomly divided into five groups: 50 microl of phosphate-buffered
      saline (PBS), PBS containing 0.02% BAK or 0.002% CKC (BAK Sol and CKC Sol,
      respectively), and emulsion containing 0.02% BAK or 0.002% CKC (BAK Em and CKC
      Em, respectively) were applied to rabbit eyes 15 times at 5-min intervals. The
      ocular surface changes induced by these eye drops were investigated using slit
      lamp examination, flow cytometry (FCM), impression cytology (IC) on conjunctiva,
      and corneal in vivo confocal microscopy (IVCM). Standard immunohistology in
      cryosections was also examined for cluster of differentiation (CD) 45+
      infiltrating and terminal deoxynucleotidyl transferase-mediated dUTP-nick end
      labeling (TUNEL)+ apoptotic cells. RESULTS: Clinical observations and IVCM showed
      that the highest toxicity was induced by BAK Sol, characterized by damaged
      corneal epithelium and a high level of inflammatory infiltration. BAK Em and CKC
      Sol presented moderate effects, and CKC Em showed the lowest toxicity with
      results similar to those of PBS. Conjunctival imprints analyzed by FCM showed a
      higher expression of RLA-DR and TNFR1 markers in BAK Sol-instilled eyes than in
      all other groups, especially at 4 h. Immunohistology was correlated with in vivo
      and ex vivo findings and confirmed this toxicity profile. A high level of
      infiltration of CD45+ inflammatory cells and TUNEL+ apoptotic cells was observed
      in limbus and conjunctiva, especially in QAC solution-receiving eyes compared to
      QAC emulsion-instilled eyes. CONCLUSIONS: The acute administration of 15
      instillations at 5 min intervals was a rapid and efficient model to assess
      quaternary ammonium toxicity profiles. This model showed the highest toxicity,
      induced by the BAK solution, and the lowest level of toxicity, induced by the CKC
      emulsion. These in vivo and ex vivo experimental approaches demonstrated that
      ocular surface toxicity was reduced by using an emulsion instead of a traditional
      solution and that a CKC emulsion was safe for future ocular administration.

PMID- 18347567
TI  - Immune modulatory activity of ribavirin for serious human metapneumovirus
      disease: early i.v. therapy may improve outcomes in immunosuppressed SCT
      recipients.

PMID- 18347568
TI  - Rituximab for passenger lymphocyte syndrome associated with allogeneic SCT.

PMID- 18347569
TI  - Prognostic value of serum surfactant protein D level prior to transplant for the
      development of bronchiolitis obliterans syndrome and idiopathic pneumonia
      syndrome following allogeneic hematopoietic stem cell transplantation.
AB  - Bronchiolitis obliterans syndrome (BOS) and idiopathic pneumonia syndrome (IPS)
      cause high mortality and impaired survival after allogeneic hematopoietic stem
      cell transplantation (allo-HSCT). Early recognition of patients at high risk of
      developing BOS/IPS may lead to improving the outcome of allo-HSCT. We
      retrospectively analyzed serum surfactant protein A, D (SP-A, -D) and Kerbs von
      Lungren 6 Ag (KL-6) levels before allo-HSCT in 56 patients who survived more than
      90 days after allo-HSCT and compared values of these serum markers and other
      transplant factors in BOS/IPS patients with those in non-BOS/IPS patients. Five
      patients developed BOS and two developed IPS at a median interval of 303 and 117
      days (range, 100-452 and 95-153) from transplantation. As a result of univariate
      analysis, pretransplant serum SP-D levels but not SP-A, KL-6 in BOS/IPS patients
      were significantly lower than those in non-BOS/IPS patients (P=0.03). In
      multivariate analysis, the patients with lower pretransplant serum SP-D level had
      a trend toward frequent development of BOS/IPS (P=0.08). Constitutive serum SP-D
      level before allo-HSCT may be a useful, noninvasive predictor for the development
      of BOS/IPS.

PMID- 18347570
TI  - Guide to Receptors and Channels (GRAC), 3rd edition.

PMID- 18347581
TI  - Involvement of hypoxia-triggered endoplasmic reticulum stress in outlet
      obstruction-induced apoptosis in the urinary bladder.
AB  - In bladder outlet obstruction (BOO), mechanical stress and ischemia/hypoxia are
      implicated in structural and functional alterations of the urinary bladder.
      Because mechanical stress and hypoxia may trigger endoplasmic reticulum (ER)
      stress, we examined involvement of ER stress in the damage of the bladder caused
      by BOO. An experimental model of BOO was established in rats by complete ligature
      of the urethra for 24 h, and bladders were subjected to northern blot analysis
      and assessment of apoptosis. Isolated urinary bladders and bladder-derived smooth
      muscle cells (BSMCs) were also exposed to mechanical strain and hypoxia and used
      for analyses. To examine involvement of ER stress in the damage of the bladder,
      the effects of a chemical chaperone 4-phenylbutyrate (4-PBA) were evaluated in
      vitro and in vivo. Outlet obstruction for 24 h induced expression of ER stress
      markers, GRP78 and CCAAT/enhancer-binding protein-homologous protein (CHOP), in
      the bladder. It was associated with induction of markers for mechanical stress
      (cyclooxygenases 2) and hypoxia (vascular endothelial growth factor and
      glyceraldehyde-3-phosphate dehydrogenase). When isolated bladders and BSMCs were
      subjected to mechanical strain, induction of GRP78 and CHOP was not observed. In
      contrast, when BSMCs were exposed to hypoxic stress caused by CoCl2 or
      thenoyltrifluoroacetone (TTFA), substantial upregulation of GRP78 and CHOP was
      observed, suggesting involvement of hypoxia in the induction of ER stress. In the
      bladder subjected to BOO, the number of terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labeling-positive cells increased in the epithelial cells
      and BSMCs. Similarly, treatment with TTFA or CoCl2 induced apoptosis of BSMCs,
      and 4-PBA significantly attenuated ER stress and apoptosis triggered by these
      agents. Furthermore, in vivo administration with 4-PBA significantly reduced
      apoptosis in the bladder subjected to BOO. These results suggested that outlet
      obstruction caused ER stress via hypoxic stress in the bladder and that hypoxia
      triggered ER stress may be involved in the induction of apoptosis in BOO.

PMID- 18347582
TI  - Conjugated linoleic acids produced by Lactobacillus dissociates IKK-gamma and
      Hsp90 complex in Helicobacter pylori-infected gastric epithelial cells.
AB  - Although probiotics have been reported to reduce the gastric inflammatory
      response to Helicobacter pylori infection, little information is available
      regarding the molecular mechanisms behind this reduction. This study investigates
      the role of conjugated linoleic acids (CLA) produced by probiotics in
      interactions of IkappaB kinase (IKK) and heat shock protein 90 (Hsp90) to
      activate the nuclear factor-kappaB (NF-kappaB) signaling pathway in human gastric
      epithelial cells infected with H. pylori. Conditioned medium (CM) containing
      Lactobacillus acidophilus-producing CLA significantly inhibited the activated NF
      kappaB signals and the upregulated expression of interleukin-8 (IL-8) in MKN-45
      cells infected with H. pylori. Pretreatment with CM with CLA attenuated the
      increased IKK activity induced by H. pylori. Transfection of siRNA for IKK-beta
      dramatically reduced H. pylori-induced IkappaBalpha phosphorylation, but siRNA
      for IKK-alpha had little effect on IkappaBalpha phosphorylation, although the
      siRNA for IKK-alpha significantly decreased IL-8 production. Furthermore, Hsp90
      was associated with IKK-alpha and IKK-gamma in H. pylori-infected cells, and CM
      with CLA dissociated the complex between Hsp90 and IKK-gamma. These results
      suggest that CLA produced by probiotics has anti-inflammatory activity in gastric
      epithelial cells infected with H. pylori via dissociation of the IKK-gamma and
      Hsp90 complex.

PMID- 18347584
TI  - Chemical biology on the brain.
AB  - A two-day symposium on chemical neurobiology revealed an open frontier for
      researchers at the interface of chemistry and neuroscience.

PMID- 18347585
TI  - Evolving biosynthetic tangos negotiate mechanistic landscapes.
AB  - The dependence of polyketide synthase and terpene cyclase mechanistic adaptation
      on the chemistry of their oligomeric substrates illuminates a convergent
      evolutionary strategy for shaping cyclization in these otherwise disparate
      reactions. Evolution of these enzyme families relies on rhythmic tangos, in which
      the enzymes and substrates together determine product outcome by negotiating
      decision networks governing intrinsic and induced chemical reactivities.

PMID- 18347586
TI  - GPIs on a chip.

PMID- 18347587
TI  - Lipids out of order.

PMID- 18347588
TI  - Fast-tracking steroid receptor crystallization.

PMID- 18347589
TI  - OTU takes the chains OUT.

PMID- 18347590
TI  - Signal transduction via unstructured protein conduits.

PMID- 18347592
TI  - Comparing whole genomes using DNA microarrays.
AB  - The rapid accumulation of complete genomic sequences offers the opportunity to
      carry out an analysis of inter- and intra-individual genome variation within a
      species on a routine basis. Sequencing whole genomes requires resources that are
      currently beyond those of a single laboratory and therefore it is not a practical
      approach for resequencing hundreds of individual genomes. DNA microarrays present
      an alternative way to study differences between closely related genomes. Advances
      in microarray-based approaches have enabled the main forms of genomic variation
      (amplifications, deletions, insertions, rearrangements and base-pair changes) to
      be detected using techniques that are readily performed in individual
      laboratories using simple experimental approaches.

PMID- 18347593
TI  - Approaches to comparative sequence analysis: towards a functional view of
      vertebrate genomes.
AB  - The comparison of genomic sequences is now a common approach to identifying and
      characterizing functional regions in vertebrate genomes. However, for theoretical
      reasons and because of practical issues, the generation of these data sets is non
      trivial and can have many pitfalls. We are currently seeing an explosion of
      comparative sequence data, the benefits and limitations of which need to be
      disseminated to the scientific community. This Review provides a critical
      overview of the different types of sequence data that are available for analysis
      and of contemporary comparative sequence analysis methods, highlighting both
      their strengths and limitations. Approaches to determining the biological
      significance of constrained sequence are also explored.

PMID- 18347594
TI  - LCN DNA: proof beyond reasonable doubt?

PMID- 18347596
TI  - Does disrupted-in-schizophrenia (DISC1) generate fusion transcripts?

PMID- 18347597
TI  - Coding SNPs included in exon arrays for the study of psychiatric disorders.

PMID- 18347598
TI  - A loss-of-function mutation in tryptophan hydroxylase 2 segregating with
      attention-deficit/hyperactivity disorder.

PMID- 18347599
TI  - Evidence of biologic epistasis between BDNF and SLC6A4 and implications for
      depression.
AB  - Complex genetic disorders such as depression likely exhibit epistasis, but neural
      mechanisms of such gene-gene interactions are incompletely understood. 5-HTTLPR
      and BDNF VAL66MET, functional polymorphisms of the serotonin (5-HT) transporter
      (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene, impact on two
      distinct, but interacting signaling systems, which have been related to
      depression and to the modulation of neurogenesis and plasticity of circuitries of
      emotion processing. Recent clinical studies suggest that the BDNF MET allele,
      which shows abnormal intracellular trafficking and regulated secretion, has a
      protective effect regarding the development of depression and in mice of social
      defeat stress. Here we show, using anatomical neuroimaging techniques in a sample
      of healthy subjects (n=111), that the BDNF MET allele, which is predicted to have
      reduced responsivity to 5-HT signaling, protects against 5-HTTLPR S allele
      induced effects on a brain circuitry encompassing the amygdala and the subgenual
      portion of the anterior cingulate (rAC). Our analyses revealed no effect of the 5
      HTTLPR S allele on rAC volume in the presence of BDNF MET alleles, whereas a
      significant volume reduction (P<0.001) was seen on BDNF VAL/VAL background.
      Interacting genotype effects were also found in structural connectivity between
      amygdala and rAC (P=0.002). These data provide in vivo evidence of biologic
      epistasis between SLC6A4 and BDNF in the human brain by identifying a neural
      mechanism linking serotonergic and neurotrophic signaling on the neural systems
      level, and have implications for personalized treatment planning in depression.

PMID- 18347600
TI  - Mode of action of mood stabilizers: is the arachidonic acid cascade a common
      target?
AB  - Bipolar disorder is a major medical, social and economic burden worldwide.
      However, the mechanisms of action of effective antibipolar disorder drugs remain
      elusive. In this paper, we review studies using a neuropharmacological approach
      in unanesthetized rats, combined with kinetic, biochemical and molecular biology
      techniques, showing that chronic administration of three Food and Drug
      Administration-approved mood stabilizers (lithium, valproate and carbamazepine)
      at therapeutically relevant doses, selectively target the brain arachidonic acid
      (AA) cascade. Whereas chronic lithium and carbamazepine decrease the binding
      activity of activator protein-2 and in turn the transcription, translation and
      activity of its AA-selective calcium-dependent phospholipase A(2) gene product,
      valproate appears to be a non-competitive inhibitor of long-chain acyl-CoA
      synthetase. The net overlapping effects of the three drugs are decreased turnover
      of AA but not of docosahexaenoic acid in rat brain phospholipids, and decreased
      brain cyclooxygenase-2 and prostaglandin E(2). Although these observations
      support the hypothesis proposed by Rapoport and colleagues that the AA cascade is
      a common target of mood stabilizers, this hypothesis is not necessarily exclusive
      of other targets. Targeting the AA cascade with drugs or diet may be a useful
      therapeutic approach in bipolar disorder, and examining the AA cascade in
      patients might help in better understanding the disease.

PMID- 18347601
TI  - Glutamate as a spectroscopic marker of hippocampal structural plasticity is
      elevated in long-term euthymic bipolar patients on chronic lithium therapy and
      correlates inversely with diurnal cortisol.
AB  - While an excess of glucocorticoids is associated with hippocampal pathology in
      mood disorders, lithium exerts robust neuroprotective and neurotrophic effects.
      Here, 21 stably remitted bipolar I patients who had been on chronic lithium
      maintenance therapy, on average, for more than a decade, and 19 carefully matched
      healthy controls were studied using 3 T (1)H-magnetic resonance spectroscopy of
      left and right hippocampus. Salivary cortisol samples were obtained to assess
      activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of
      N-acetylaspartate (NAA), choline-containing compounds and total creatine were
      similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate
      concentrations were significantly increased as an effect of patient status
      (patients>controls) and laterality (left hippocampus>right hippocampus).
      Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across
      groups and within the patient group, diurnal saliva cortisol levels showed a
      significant inverse relationship with both Glu and NAA. Taken together, these
      results add to the concept of bipolar disorder as an illness involving disturbed
      hippocampal structural plasticity under the opposing influences of lithium and
      glucocorticoids.

PMID- 18347603
TI  - Sleep patterns and television viewing in relation to obesity and blood pressure:
      evidence from an adolescent Brazilian birth cohort.
AB  - BACKGROUND: Disruption of circadian rhythms has been associated with obesity in
      children and adolescents, and with hypertension in adults, in industrialized
      populations. OBJECTIVE: We examined cross-sectional associations between sleep
      duration or television viewing and obesity and blood pressure in Brazilian
      adolescents. DESIGN: The sample consisted of 4452 adolescents aged 10-12 years
      participating in a prospective birth cohort study in Pelotas, Brazil. Sleep
      duration and television viewing were determined through questionnaires. Obesity
      was assessed using international cut-offs for body mass index (BMI), and body
      fatness by skinfold thicknesses. Blood pressure was measured using a validated
      monitor. RESULTS: Short sleep duration was associated with increased BMI,
      skinfolds, systolic blood pressure, activity levels and television viewing. Each
      hour of sleep reduced BMI by 0.16 kg/m(2) (s.e. 0.04), and was associated with
      odds ratio for obesity of 0.86 (s.e. 0.04), both P<0.001. Television viewing was
      associated with increased BMI and skinfolds, and increased blood pressure. The
      effects of sleep duration and television viewing on obesity were independent of
      one another. Their associations with blood pressure were mediated by body
      fatness. CONCLUSIONS: Both short sleep duration and increased television viewing
      were associated with greater body fatness, obesity and higher blood pressure,
      independently of physical activity level. These associations were independent of
      maternal BMI, identified in other studies as the strongest predictor of childhood
      obesity. Our study shows that behavioural factors associated with metabolic risk
      in industrialized populations exert similar deleterious effects in a population
      undergoing nutritional transition and suggest options for public health
      interventions.

PMID- 18347602
TI  - Genomewide association for schizophrenia in the CATIE study: results of stage 1.
AB  - Little is known for certain about the genetics of schizophrenia. The advent of
      genomewide association has been widely anticipated as a promising means to
      identify reproducible DNA sequence variation associated with this important and
      debilitating disorder. A total of 738 cases with DSM-IV schizophrenia (all
      participants in the CATIE study) and 733 group-matched controls were genotyped
      for 492,900 single-nucleotide polymorphisms (SNPs) using the Affymetrix 500K two
      chip genotyping platform plus a custom 164K fill-in chip. Following multiple
      quality control steps for both subjects and SNPs, logistic regression analyses
      were used to assess the evidence for association of all SNPs with schizophrenia.
      We identified a number of promising SNPs for follow-up studies, although no SNP
      or multimarker combination of SNPs achieved genomewide statistical significance.
      Although a few signals coincided with genomic regions previously implicated in
      schizophrenia, chance could not be excluded. These data do not provide evidence
      for the involvement of any genomic region with schizophrenia detectable with
      moderate sample size. However, a planned genomewide association study for
      response phenotypes and inclusion of individual phenotype and genotype data from
      this study in meta-analyses hold promise for eventual identification of
      susceptibility and protective variants.

PMID- 18347604
TI  - Infection-induced inflammatory response of adipocytes in vitro.
AB  - BACKGROUND: Abdominal obesity plays an important role in the development of
      insulin resistance, diabetes mellitus and atherosclerosis. The exact
      pathophysiological mechanisms are unclear but adipocyte dysfunction is thought to
      be crucial. Infections are associated with the development of atherosclerosis as
      well as diabetes. In this study we investigated whether adipocytes can be
      infected and whether this results in production of inflammatory cytokines
      relevant for the development of atherosclerosis and diabetes. METHODS: Pre
      adipocytes were cultured and differentiated into mature adipocytes in vitro.
      Adipocytes and pre-adipocytes were incubated with infective and heat-inactivated
      Chlamydia pneumoniae, cytomegalovirus (CMV), adenovirus (Ad) subtypes 2 and 36,
      influenza A and respiratory syncitial virus (RSV). After 48 h, adiponectin,
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and plasminogen
      activator inhibitor-1 (PAI-1) were measured in supernatants. RESULTS: Infection
      of adipocytes with Ad-36, CMV and RSV resulted in increased IL-6 production from
      192+/-22 pg ml(-1) (uninfected) to 1030+/-86 pg ml(-1), 838+/-59 pg ml(-1) and
      1241+/-191 pg ml(-1), respectively (all P<0.01 vs control). In addition, Ad-36
      infection slightly reduced PAI production in adipocytes (285+/-26.8 ng ml(-1) vs
      uninfected: 477+/-71.2 ng ml(-1); P=0.05) and pre-adipocytes (709+/-43.3 ng ml(
      1) vs uninfected: 1071+/-71.8 ng ml(-1); P<0.01). In contrast, human Ad type 2
      did not exert any effect on IL-6 or PAI production. None of the microorganisms
      induced significant changes in adiponectin and/or TNF-alpha production.
      CONCLUSIONS: Adipocytes can be infected with several microorganisms in vitro.
      Infection of adipocytes with Ad-36, but not Ad-2 leads to increased production of
      IL-6 which might contribute to chronic low-grade inflammation, a process known to
      be involved in the development of cardiovascular diseases and type 2 diabetes.

PMID- 18347605
TI  - Obesity treatment and cardiovascular prevention in mentally retarded subjects.

PMID- 18347606
TI  - The use of tracheal stoma stents in high spinal cord injury: a patient-friendly
      alternative to long-term tracheostomy tubes.
AB  - STUDY DESIGN: Case series. SETTING: North West Regional Spinal Injuries Unit,
      Southport and Formby District General Hospital, UK. OBJECTIVES: To identify a
      novel type of tracheal stents for use in patients with high spinal cord injury.
      Patients with high spinal cord injury (above C4) frequently have significant
      respiratory impairment and may require long-term access to the trachea for
      respiratory support. For the most part, tracheostomy tubes are used for this
      purpose but a tracheal stoma stent can offer a suitable alternative in selected
      cases and deserves wider recognition. METHODS: Following completion of a patient
      questionnaire survey, the authors describe the use of stoma stents in nine
      patients, five of whom had full-time diaphragm pacing. The stent in these cases
      is for retention of access for positive pressure ventilation, and for the
      prevention of obstructive sleep apnoea. This was also the indication in one self
      ventilating patient with tetraplegia and sleep apnoea. Two patients with
      recurrent chest infections, in whom chest physiotherapy was difficult, benefited
      from the stoma stents. One patient, after ventilator weaning, required a further
      4 months of tracheal access on account of episodic hypoventilation and
      temporarily had a tracheal stent as an inpatient. CONCLUSION: Patients who have
      had the benefit of tracheal stents report significant improvement in relation to
      local discomfort, tracheobronchial secretions and vocalization. With suitable
      training, the stents can be changed and cleaned easily in the home setting.

PMID- 18347607
TI  - Can cell therapy heal a spinal cord injury?
AB  - STUDY DESIGN: Literature survey. OBJECTIVES: To summarize and discuss current
      possibilities and success rates for the treatment of spinal cord injury in animal
      models. SETTINGS: University of Antwerp, Belgium. METHODS: We searched Pubmed for
      publications from 1997 onwards. Seven older papers were used for completion of
      data. RESULTS: Despite major progress in pharmacological and surgical approaches,
      a spinal cord injury still remains a very complex medical and psychological
      challenge, both for the patients and their relatives, as well as for the involved
      physicians, with currently no existing curative therapy. For a future efficient
      treatment, one has to consider and combine four main approaches: (1) tissue or
      cell transplantation, (2) providing growth-stimulating factors (neurotrophic
      factors), (3) blocking factors which inhibit neural regeneration and (4)
      modulation of inflammatory response following spinal cord injury. CONCLUSIONS:
      Although different treatment options have proven to be successful in animal
      models, they also provide a realistic view on a complex therapeutical approach,
      which needs to be further investigated in many carefully designed animal studies
      before human applications can be considered.

PMID- 18347608
TI  - Non-invasive assessment of lower extremity muscle composition after incomplete
      spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional study. OBJECTIVE: (1) To quantify intramyocellular
      lipid (IMCL) content of the soleus muscle. (2) To assess the T(2) relaxation
      rates in the lower extremity skeletal muscles in persons with incomplete spinal
      cord injury (SCI). SETTING: Academic Institution, Florida. METHODS: Eight
      subjects (42+/-10 years old; 70+/-12 kg; 176+/-10 cm) with chronic (17+/-9 months
      post injury) motor SCI (C4-T12; ASIA C or D) and eight matched healthy controls
      were tested. Localized unsuppressed proton spectroscopy (H-MRS) was performed to
      estimate total lipid content and individual lipid components; IMCL and
      extramyocellular lipid (EMCL) from the soleus muscle. T(2)-weighted imaging of
      lower extremity muscles yielded muscle T(2) rates. RESULTS: The IMCL content of
      the soleus muscle was 3.3 times higher in the patient group as compared to
      controls (P=0.002; 0.0401 (0.0234-0.0849) versus 0.0123 (0.0090-0.0175)).
      Similarly, EMCL measures were 4.5 times higher as compared to the controls
      (P=0.002). Significant differences were observed in the T(2) relaxation times of
      the soleus and gastrocnemius muscles (P<0.05). CONCLUSION: The increased levels
      of IMCL might interfere with the glucose uptake in skeletal muscle; potentially
      predisposing persons with incomplete SCI to the development of peripheral insulin
      resistance. Marked elevations in the T(2) relaxation times of the locomotor
      muscles are reflective of an altered muscle composition.

PMID- 18347609
TI  - Dendritic cells: driving the differentiation programme of T cells in viral
      infections.
AB  - Protective immunity against viral pathogens depends on the generation and
      maintenance of a small population of memory CD8(+) T cells. Successful memory
      cell generation begins with early interactions between naive T cell and dendritic
      cells (DCs) within the inflammatory milieu of the secondary lymphoid tissues.
      Recent insights into the role of different populations of DCs, and kinetics of
      antigen presentation, during viral infections have helped to understand how DCs
      can shape the immune response. Here, we review the recent progress that has been
      made towards defining how specific DC subsets drive effector CD8(+) T-cell
      expansion and differentiation into memory cells. Further, we endeavour to examine
      how the molecular signals imparted by DCs coordinate to generate protective
      CD8(+) T-cell immunity.

PMID- 18347610
TI  - Further evidence for association of the RGS2 gene with antipsychotic-induced
      parkinsonism: protective role of a functional polymorphism in the 3'-untranslated
      region.
AB  - RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal
      transduction. Functional variants in the gene may influence susceptibility to
      extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further
      investigate our previous report of association of the RGS2 gene with
      susceptibility to antipsychotic-induced EPS, we performed a replication study.
      EPS were rated in 184 US patients with schizophrenia (115 African Americans, 69
      Caucasian) treated for at least a month with typical antipsychotic drugs (n=45),
      risperidone (n=46), olanzapine (n=50) or clozapine (n=43). Six single nucleotide
      polymorphisms (SNPs) within or flanking RGS2 were genotyped (rs1933695,
      rs2179652, rs2746073, rs4606, rs1819741 and rs1152746). Odds ratios (ORs) and 95%
      confidence intervals (CIs) were calculated by logistic regression. Our results
      indicate association of SNP rs4606 with antipsychotic-induced parkinsonism (AIP),
      as measured by the Simpson Angus scale, in the overall sample and in the African
      American subsample, the G (minor) allele having a protective effect. ORs for AIP
      among rs4606 G-allele carriers were 0.23 (95% CI 0.10-0.54, P=0.001) in the
      overall sample, and 0.20 (0.07-0.57, P=0.003) in the African-American subsample.
      In the previously studied Israeli sample the OR was 0.31 (0.11-0.84, P=0.02). We
      completely sequenced the RGS2 gene in nine patients with AIP and nine patients
      without, from the Israeli sample. No common coding polymorphisms or additional
      regulatory variants were revealed, suggesting that association of the rs4606 C/G
      polymorphism with AIP is biologically meaningful and not a consequence of linkage
      disequilibrium with another functional variant. Taken together, the findings of
      the current study support the association of RGS2 with AIP and focus on a
      possible protective effect of the minor G allele of SNP rs4606. This SNP is
      located in the 3'-regulatory region of the gene, and is known to influence RGS2
      mRNA levels and protein expression.

PMID- 18347611
TI  - Interaction between polymorphisms in the renin-angiotensin-system and angiotensin
      converting enzyme inhibitor or beta-blocker use and the risk of myocardial
      infarction and stroke.
AB  - This study investigates whether the interaction between angiotensin-converting
      enzyme (ACE) inhibitors or beta-blockers and the ACE insertion/deletion (I/D)
      polymorphism or angiotensin receptor II type 1 (AGTR1) 573C/T polymorphism
      modifies the risk of myocardial infarction (MI) or stroke. In total, 4097
      subjects with hypertension were included in this study. The drug-gene interaction
      on the risk of MI or stroke was determined with a Cox proportional hazard model.
      The risk of MI was reduced in current users of ACE inhibitors with the AGTR1
      573CT or CC genotype compared to ACE inhibitors with the AGTR1 573TT genotype
      (synergy index (SI):0.32; 95% confidence interval (CI): 0.14-0.70). No
      significant drug-gene interaction was found on the risk of stroke (SI:0.82; 95%
      CI: 0.44-1.52) or in beta-blocker users. Also, no significant drug-gene
      interaction was found with the ACE I/D polymorphism. In conclusion, subjects with
      at least one copy of the AGTR1 573C allele might have more benefit from ACE
      inhibitor therapy.

PMID- 18347612
TI  - Cost-effectiveness of pharmacogenetic testing to tailor smoking-cessation
      treatment.
AB  - We evaluated the cost-effectiveness of a range of smoking cessation drug
      treatments, including varenicline, transdermal nicotine (TN), bupropion and the
      use of a genetic test to choose between TN and bupropion. We performed Monte
      Carlo simulation with sensitivity analysis, informing analyses with published
      estimates of model parameters and current prices for genetic testing and smoking
      cessation therapy. The primary outcomes were discounted life-years (LY) and
      lifetime tobacco-cessation treatment costs. In the base case, varenicline
      treatment was optimal with an ICER, compared to bupropion, of $2985/LY saved. In
      sensitivity analyses, varenicline was in all cases (and bupropion in most cases)
      admissible; only under favorable assumptions was the genetically tailored
      approach competitive. Our data suggest that an untailored approach of treatment
      with either bupropion or varenicline is a cost-effective form of tobacco
      dependence treatment, but a tailored approach for selecting between TN and
      bupropion can be cost-effective under plausible assumptions.

PMID- 18347613
TI  - Migratory properties of cultured olfactory ensheathing cells by single-cell
      migration assay.
AB  - Olfactory ensheathing cells (OECs) are a unique type of glial cells that have
      axonal growth-promoting properties. OEC transplantation has emerged as a
      promising experimental therapy of axonal injuries and demyelinating diseases.
      However, some fundamental cellular properties of OECs remain unclear. In this
      study, we found that the distinct OEC subpopulations exhibited different
      migratory properties based on time-lapse imaging of single isolated cells,
      possibly due to their different cytoskeletal organizations. Moreover, OEC
      subpopulations displayed different attractive migratory responses to a gradient
      of lysophosphatidic acid (LPA) in single-cell migration assays. Finally, we found
      that OEC subpopulations transformed into each other spontaneously. Together,
      these results demonstrate, for the first time to our knowledge, that distinct OEC
      subpopulations display different migratory properties in vitro and provide new
      evidence to support the notion of OECs as a single cell type with malleable
      functional phenotypes.

PMID- 18347614
TI  - The roles of MAPKs in disease.
AB  - MAP kinases transduce signals that are involved in a multitude of cellular
      pathways and functions in response to a variety of ligands and cell stimuli.
      Aberrant or inappropriate functions of MAPKs have now been identified in diseases
      ranging from cancer to inflammatory disease to obesity and diabetes. In many cell
      types, the MAPKs ERK1/2 are linked to cell proliferation. ERK1/2 are thought to
      play a role in some cancers, because mutations in Ras and B-Raf, which can
      activate the ERK1/2 cascade, are found in many human tumors. Abnormal ERK1/2
      signaling has also been found in polycystic kidney disease, and serious
      developmental disorders such as cardio-facio-cutaneous syndrome arise from
      mutations in components of the ERK1/2 cascade. ERK1/2 are essential in well
      differentiated cells and have been linked to long-term potentiation in neurons
      and in maintenance of epithelial polarity. Additionally, ERK1/2 are important for
      insulin gene transcription in pancreatic beta cells, which produce insulin in
      response to increases in circulating glucose to permit efficient glucose
      utilization and storage in the organism. Nutrients and hormones that induce or
      repress insulin secretion activate and/or inhibit ERK1/2 in a manner that
      reflects the secretory demand on beta cells. Disturbances in this and other
      regulatory pathways may result in the contribution of ERK1/2 to the etiology of
      certain human disorders.

PMID- 18347615
TI  - Keratoprosthesis in the treatment of severe ocular trauma.

PMID- 18347616
TI  - Circulating uveal melanoma cells: should we test for them?

PMID- 18347618
TI  - The Boston Keratoprosthesis in severe ocular trauma.
AB  - BACKGROUND: In eyes with corneal disease and opacity so severe that standard
      corneal transplantation carries a poor prognosis, a keratoprosthesis (KPro) may
      still be successful in providing functional visual acuity. The purpose of this
      study was to determine the outcome of Boston KPro implantation in the
      rehabilitation of severe ocular trauma. METHODS: This is a retrospective study of
      30 eyes (30 patients) with severe ocular trauma that underwent Boston KPro type I
      implantation at the Massachusetts Eye and Ear Infirmary. Of these 30 eyes, 6 had
      mechanical trauma, 21 had chemical burns, and 3 had thermal burns. The measures
      used in this review are 5-fold: (i) anatomic success; (ii) number of
      postoperative repair procedures performed; (iii) preoperative and postoperative
      visual acuity; (iv) number of eyes with concomitant preoperative retinal or optic
      nerve damage prior to KPro surgery; and (v) incidence of postoperative
      complications. RESULTS: Preoperative visual acuity ranged from counting fingers
      to light perception (median: hand motion). Best-corrected postoperative visual
      acuity ranged from 20/20 to no light perception (median: 20/80). Anatomic success
      was achieved in 5 out of 5 mechanically traumatized eyes, 14 out of 17 eyes with
      chemical burns, and 3 out of 3 eyes with thermal burns. Repair procedures were
      done in 8 of the 17 chemically burned eyes. The number of eyes with concomitant
      preoperative ocular disease was 2 out of 6 in the mechanical trauma group, 10 out
      of 21 in the chemical burn group, and 1 out of 3 in the thermal burn group. The
      incidence of postoperative complications was greater in the chemical burn group
      than in either the mechanical trauma or the thermal burn group. INTERPRETATION:
      The Boston KPro can provide considerable visual improvement and a long-term
      anatomic retention rate in severely traumatized eyes. The overwhelming danger in
      severe chemical burns is glaucoma progression despite a functioning tube implant
      and normal intraocular pressure.

PMID- 18347619
TI  - Blepharitis: current strategies for diagnosis and management.
AB  - BACKGROUND: The aim of this article is to present a consensus on the appropriate
      identification and management of patients with blepharitis based on expert
      clinical recommendations for 4 representative case studies and evidence from well
      designed clinical trials. METHODS: The case study recommendations were developed
      at a consensus panel meeting of Canadian ophthalmologists and a guest
      ophthalmologist from the U.K., with additional input from family doctors and an
      infectious disease/medical microbiologist, which took place in Toronto in June
      2006. A MEDLINE search was also conducted of English language articles describing
      randomized controlled clinical trials that involved patients with blepharitis.
      RESULTS: Blepharitis involving predominantly the skin and lashes tends to be
      staphylococcal and (or) seborrheic in nature, whereas involvement of the
      meibomian glands may be either seborrheic, obstructive, or a combination (mixed).
      The pathophysiology of blepharitis is a complex interaction of various factors,
      including abnormal lid-margin secretions, microbial organisms, and abnormalities
      of the tear film. Blepharitis can present with a range of signs and symptoms, and
      is associated with various dermatological conditions, namely, seborrheic
      dermatitis, rosacea, and eczema. The mainstay of treatment is an eyelid hygiene
      regimen, which needs to be continued long term. Topical antibiotics are used to
      reduce the bacterial load. Topical corticosteroid preparations may be helpful in
      patients with marked inflammation. INTERPRETATION: Blepharitis can present with a
      range of signs and symptoms, and its management can be complicated by a number of
      factors. Expert clinical recommendations and a review of the evidence on
      treatment supports the practice of careful lid hygiene, possibly combined with
      the use of topical antibiotics, with or without topical steroids. Systemic
      antibiotics may be appropriate in some patients.

PMID- 18347620
TI  - Age-related macular degeneration and low-vision rehabilitation: a systematic
      review.
AB  - BACKGROUND: Because of the prevalence and devastating consequences of age-related
      macular degeneration (AMD), a systematic review devoted to low-vision
      rehabilitation and AMD seems timely and appropriate. METHODS: Several electronic
      databases were searched for studies from 1980 to 2006 involving individuals with
      low vision or visual impairment and rehabilitation interventions. Studies were
      assessed for quality and level of evidence. RESULTS: The findings indicate that
      standard low-vision rehabilitation programs, conventional in-clinic assessments,
      and optical devices are effective ways of managing and living with vision loss.
      Areas of unmet need include determining which types of orientation and mobility
      programs and devices are most effective and developing methods of matching
      assistive technologies with the individual's visual and environmental
      requirements. INTERPRETATION: Additional randomized controlled trials with
      similar intervention comparisons and outcome measures are needed to form stronger
      conclusions for the most effective low-vision rehabilitation interventions for
      individuals with AMD.

PMID- 18347621
TI  - A screening strategy for the detection of sickle cell retinopathy in pediatric
      patients.
AB  - BACKGROUND: Children with sickle cell hemoglobinopathy are referred routinely to
      detect retinopathy and thereby prevent vision-threatening complications. This
      study aimed to determine the prevalence and age of onset of clinically
      significant retinopathy in such patients, and to recommend a screening strategy
      for ophthalmologists. METHODS: Two hundred sixty-three pediatric sickle cell
      patients to a maximum age of 18 years during the period of observation were
      reviewed for the onset of retinopathy, considering the influence of hemoglobin
      genotype, gender, and the presence of systemic manifestations. RESULTS:
      Proliferative retinopathy (PR) was rare. Six cases (8.2%) of PR were seen in the
      SC genotype, 1 case (0.6%) in the SS genotype, and no cases in the SB-Thalassemia
      genotype. The age of onset of PR was a mean of 13.7 years (median 13, range 9-18)
      in the SC genotype and 16 years in the SS genotype. Neither gender nor the
      presence of systemic manifestations was predictive for the prevalence or age of
      onset of retinopathy. INTERPRETATION: Screening for retinopathy may begin at age
      9 years for SC genotype patients and at age 13 years for SS and SB-Thalassemia
      genotype patients. Serial examinations may be done biennially for eyes with
      normal findings. Patients with an abnormal examination should undergo fluorescein
      angiography and be followed as necessary.

PMID- 18347622
TI  - Combined rhegmatogenous and traction retinal detachment in proliferative diabetic
      retinopathy: clinical manifestations and surgical outcome.
AB  - BACKGROUND: Combined rhegmatogenous and traction retinal detachment (combined
      detachment) is a serious complication in proliferative diabetic retinopathy. The
      common clinical findings and surgical results of this complication were
      investigated. METHODS: Forty eyes of 36 consecutive patients with combined
      detachment undergoing pars plana vitrectomy at a teaching hospital in a 4.5-year
      period were retrospectively reviewed. All cases had been followed up for at least
      6 months. RESULTS: Only 10 of the 40 cases had a preoperative visual acuity
      better than finger counting vision. Extensive proliferation with multiple,
      thickened, plaque-like vitreoretinal adhesions and large areas of detachment were
      noted in 38 cases, 19 cases showing predominantly fibrous tissue and 19 cases
      presenting with predominantly active fibrovascular proliferation. Two cases had
      minimal fibrovascular proliferation. Retinal breaks were identified in 7 eyes
      (17.5%) before surgery and in 33 eyes (82.5%) during surgery. Thirty-seven eyes
      (92.5%) achieved long-term retinal reattachment. Silicone oil was used in 23 eyes
      (57.5%). Visual acuity improved in 28 eyes (70%), was unchanged in 6 (15%), and
      became worse in 6 (15%). In 19 eyes postoperative vision was better than 20/400.
      Multiple regression analysis showed preoperative visual acuity as the single
      factor associated with postoperative visual outcome. INTERPRETATION: Combined
      retinal detachment in proliferative diabetic retinopathy may occur during the
      stage of active fibrovascular proliferation or as a late complication. It is
      frequently associated with tightly adherent preretinal tissue and extensive
      detachment. Preoperative visual acuity best predicts visual prognosis.

PMID- 18347623
TI  - Retina remodeling following diode laser.
AB  - BACKGROUND: The purpose of this study was to characterize the sequential
      development of focal and surround retinal injury and repair following
      transscleral diode laser to rat retina. METHODS: Transscleral laser
      photocoagulation of the retina was induced with a diode laser (DioPexy Probe, 810
      nm, 200 mW, 2 seconds) in adult Long-Evans rats. The right eye of rats with
      survival times of 0 days (n = 4), 5 days (n = 6), 2 weeks (n = 4), 6 weeks (n =
      6), and 12 weeks (n = 4) was studied. Using serial sections, detailed
      pathological changes in laser-treated and surrounding retinal and choroidal areas
      were compared with the control fellow eye. RESULTS: Photocoagulation damage was
      limited to the retina, sparing Bruch's membrane, with minimal choroidal
      involvement in almost all cases (23/24 eyes). Following damage to the neural
      retina, the sequence of major remodeling processes was consistent and included
      inflammatory response, reparative changes, and formation of glial-vascular scar
      with neovascularization. INTERPRETATION: This new laser model caused reproducible
      injury, inflammation, and scarring confined to the retina, and may be a tool to
      help test the effects of candidate neuroprotective/regenerative agents on retinal
      degeneration to prevent vision loss.

PMID- 18347624
TI  - Variants of RP1 gene in Chinese patients with autosomal dominant retinitis
      pigmentosa.
AB  - BACKGROUND: The objective of this study was to determine the frequency and
      characteristics of mutations in the RP1 gene and to characterize mutations with
      the clinical features in the Chinese family with autosomal dominant retinitis
      pigmentosa (ADRP). METHODS: Forty-three affected, unrelated Chinese individuals
      with ADRP were recruited between 2002 and 2006. Polymerase chain reaction and
      direct DNA sequencing were used to screen in the entire coding region and splice
      sites of the RP1 gene. Cosegregation analysis and population frequency studies
      were performed for patients with identified mutations. The clinical features were
      determined by complete ophthalmologic examinations. RESULTS: The mutation
      detectable rate of the RP1 gene in Chinese patients with ADRP was 1/43. A
      missense mutation, N985Y, was identified in exon 4 of the RP1 gene in 8 affected
      individuals from a Chinese family with ADRP. The ophthalmic findings with an
      N985Y mutation were similar to those of typical retinitis pigmentosa with delayed
      onset after age 40 years and slow progression. In addition, a total of 9 distinct
      variants were detected in our study population, most of which were RP1 gene
      polymorphisms; the pathological significance of P903L, a novel missense mutation,
      was unconfirmed. INTERPRETATION: Mutations in the RP1 gene are relatively rare in
      Chinese patients with ADRP. In our cases, N985Y mutation segregated with the
      phenotype from 1 Chinese family with mild and late-onset ADRP, a finding that has
      not been documented in other races.

PMID- 18347625
TI  - Cost-effectiveness of reducing wait times for cataract surgery in Ontario.
AB  - BACKGROUND: Reducing wait times for cataract surgery is a priority in Ontario.
      However, no previous analysis has determined whether the extra treatment volumes
      required to reduce wait times are of good monetary value when compared with
      allocating those same financial resources to new programs, drugs, or
      technologies. The objective of the study was to use queuing models to determine
      the cost-effectiveness of reducing, to target levels, wait times for cataract
      surgery at the provincial level within 1 to 10 years by increasing treatment
      volumes. METHODS: A cost-effectiveness analysis was performed by estimating the
      extra treatment volume required to reduce wait times using queuing model
      methodology. The cost of these extra treatments was obtained from Ontario
      provincial data. The incremental benefits of surgery are improvements in quality
      adjusted life years (QALYs), and these values were obtained from the clinical
      literature. Incremental costs were compared with incremental benefits to
      determine an incremental cost-effectiveness ratio. RESULTS: To reach the publicly
      stated target wait times, annual treatment volumes must increase by 4%. An extra
      increase in treatment volumes of 25,660 must also be provided for the transition
      period from the current wait time. The incremental cost-effectiveness ratio is
      $17,829 per QALY if the target wait time is achieved in 5 years, and this ratio
      is less than the common threshold for approval of new interventions, of $50,000
      per QALY. INTERPRETATION: Increasing treatment volumes is a cost-effective way of
      reducing wait times.

PMID- 18347626
TI  - Medical students' attitudes on diversity when applying to Toronto's ophthalmology
      residency program.
AB  - BACKGROUND: Affirmative action is a controversial admissions policy practised by
      universities in the United States and other countries around the world. It is
      currently not used at the University of Toronto ophthalmology residency program.
      A survey was conducted to determine the opinions of applicants as to the role
      that affirmative action and quotas should play during the admissions process and
      to determine the current ethnic breakdown of the applicants to ophthalmology.
      METHODS: A survey of 14 questions was sent out to all 72 medical students
      applying for a residency position in our program. The response rate was 58%. The
      students were asked to agree or disagree on a 5-point Likert scale with
      statements related to ethnicity, gender, and whether affirmative action policies
      exist or should exist for certain groups. RESULTS: The majority of the
      respondents (26/42, 62%) considered themselves an ethnic minority, and 57%
      (24/42) considered themselves a visible minority. Most (32/42) felt that the sex
      of the applicant should not play a role in the selection process. Only 24%
      (10/42) supported affirmative action, and only 12% (5/42) supported quotas for
      minority applicants. INTERPRETATION: The majority of survey respondents in this
      study did not support affirmative action or quotas at the University of Toronto
      ophthalmology program. The applicants to this program represent a diverse group
      of individuals from a multitude of ethnic, cultural, and racial backgrounds, and,
      in their average opinion, affirmative action policies would not benefit our
      admissions program.

PMID- 18347627
TI  - Finger massage versus a novel massage device after trabeculectomy.
AB  - BACKGROUND: Ocular massage is a common technique employed after trabeculectomy to
      aid filtration. This pilot study compares a novel ocular massage device (MD) with
      finger massage (FM) after trabeculectomy. The device provides the patient with
      audio feedback about correctly applied force, and the force applied can be
      customized for each patient. METHODS: A prospective, randomized study was
      performed comparing the effects of FM versus MD on intraocular pressure (IOP) and
      complication rates. All patients were given a standardized tutorial in ocular
      massage. The efficiency of their massage technique was evaluated at 1 week by
      having the patient perform the massage in front of the ophthalmologist, with IOP
      measurements taken before and after massage. Information on bleb morphology, IOP,
      ocular medications, and complications were recorded on a weekly basis. The
      patient perspective was recorded by questionnaire at 1 week, 1 month, and 3
      months after initiation of the massage. RESULTS: Twenty-five patients were
      enrolled in the study, 12 randomly assigned to the FM and 13 to the MD groups.
      Patients in the MD group were much more confident that they were doing the
      massage correctly (p = 0.009) and reported a greater ease of use and lower pain
      scores. The mean difference in IOP in the 2 groups was not statistically
      significant in the first 3 weeks, and IOP after 3 months was statistically
      similar in both groups. Laser suture lysis was performed in 8 patients (66%) in
      the FM versus 6 (46%) in the MD group (p = 0.42). Wound leaks developed in 4
      patients (3 in the FM group vs. 1 in the MD group, p = 0.32). INTERPRETATION: The
      massage device shows promise as an adjunctive tool in the postoperative
      management of trabeculectomies.

PMID- 18347628
TI  - Bleb needle redirection for the treatment of early postoperative trabeculectomy
      leaks: a novel approach.
AB  - BACKGROUND: This study describes a technique of bleb needling as a management of
      early postoperative limbal bleb leaks unresponsive to conservative management.
      This technique redirects the aqueous into a newly formed bleb, sealing the leak
      easily and rapidly. METHODS: Medical records of patients with early bleb leaks
      after trabeculectomy or phacotrabeculectomy between November 2004 and September
      2005 were reviewed retrospectively. Patients whose bleb leaks were unresponsive
      to conservative management and who underwent needling procedures were identified
      and studied further. RESULTS: Six of 18 patients who had early bleb leaks did not
      respond to conservative treatment and underwent a needle redirection of their
      blebs, which sealed within a few days after needling. The mean follow-up time of
      this group was 6 months. The mean preoperative vision was 20/50 with a mean
      preoperative intraocular pressure (IOP) of 27 using 2.8 medications, and this
      improved postoperatively and postneedling to a vision of 20/30 with a mean IOP of
      11 using 0.16 medications. INTERPRETATION: Bleb needling with subsequent
      redirection of aqueous into a new bleb should be considered as an option in the
      treatment of limbal leaks after a trabeculectomy that does not respond to
      conservative treatment.

PMID- 18347629
TI  - Ring melanoma of the ciliary body: clinical and ultrasound biomicroscopic
      characteristics.
AB  - BACKGROUND: Diagnosis of ring melanoma is clinically difficult since the mass can
      remain hidden with standard slit-lamp biomicroscopy. The aim of this study was to
      evaluate the utility of ultrasound biomicroscopy (UBM) as a diagnostic tool for
      ring melanoma of the ciliary body. METHODS: This was a retrospective study of 6
      eyes of 6 patients at Princess Margaret Hospital, Toronto, Ont., with a diagnosis
      of ring melanoma of the ciliary body. The tumor extension was measured
      clinically, gonioscopically, ultrasonographically (by UBM), and pathologically.
      RESULTS: Since 2000, 6 cases of ring melanoma have been diagnosed at Princess
      Margaret Hospital: 2 women and 4 men, median age 57 years. Five patients
      presented as uncontrolled hyperchromic glaucoma (83%). Ciliary body involvement
      on slit-lamp examination ranged from 60 to 180 degrees. Ciliary body involvement
      as assessed by UBM ranged from 180 to 300 degrees. Tumor extension according to
      pathological examination ranged from 210 to 360 degrees. With these measures, the
      ring melanoma clinical criteria were not filled by 5 patients. INTERPRETATION:
      UBM is an important tool in determining the extent of ciliary body involvement
      and classifying these lesions.

PMID- 18347630
TI  - Transconjunctival orbitotomy for orbital cavernous hemangiomas.
AB  - BACKGROUND: Orbital cavernous hemangiomas, particularly those within the
      retrobulbar space, are approached by neurosurgeons as well as by ophthalmic
      surgeons. Several surgical techniques have been applied over the past decades.
      Less traumatic approaches in this functionally and cosmetically important region
      are desirable. We describe a transconjunctival approach in 39 patients with
      orbital cavernous hemangiomas. METHODS: Thirty-nine patients with orbital
      cavernous hemangiomas were treated with transconjunctival orbitotomy. The
      clinical and radiologic characteristics of orbital cavernous hemangiomas were
      analyzed in the course of their appropriate treatment. RESULTS: In all patients,
      cavernous hemangiomas were just behind the globe or were compressing it. Computed
      tomography and magnetic resonance imaging showed orbital cavernous hemangiomas as
      round, well-defined intraconal masses. In 37 cases, the tumors were removed
      intact, and only 1 patient suffered permanent vision loss as a result of
      intraoperative hemorrhage. In the other 2 cases, the tumor fragments were
      incompletely removed. Visual acuity increased in 6 of the 9 cases with primary
      visual impairment. Thirty-two patients with primary proptosis were resolved
      completely. Six patients with visual field defect were also improved.
      INTERPRETATION: Retrobulbar intraconal cavernous hemangiomas can be removed
      successfully through a transconjunctival approach. However, if the tumor is close
      to, or touching, the orbital apex, adhering tightly to retrobulbar tissue, or
      combined with large draining veins, operation through other approaches must be
      considered.

PMID- 18347632
TI  - Paracentesis before intravitreal injection of bevacizumab.

PMID- 18347633
TI  - Eyelid primary diffuse large B-cell lymphoma.

PMID- 18347634
TI  - Vision health: seeing how medical students can contribute.

PMID- 18347635
TI  - Chloroquine-related myasthenic syndrome with severe retinopathy.

PMID- 18347636
TI  - Paraneoplastic downbeat nystagmus.

PMID- 18347637
TI  - Management of Coats disease with bevacizumab in 2 patients.

PMID- 18347638
TI  - Retinal angiomatous proliferation complicated by pigment epithelial tear
      following intravitreal bevacizumab treatment.

PMID- 18347639
TI  - Comparison of wavefront analysis between monofocal and multifocal posterior
      chamber implants.

PMID- 18347640
TI  - One surgeon's experience with hydrophilic and hydrophobic intraocular lens
      implantation using the Monarch II injector.

PMID- 18347641
TI  - Choroidal melanoma in association with juxtapapillary melanocytoma.

PMID- 18347642
TI  - Low-grade, aggressive fibrous histiocytoma of the medial canthus.

PMID- 18347643
TI  - Self-drainage of a posttrabeculectomy choroidal effusion: loss of protective
      effect.

PMID- 18347644
TI  - Medulloepithelioma of the ciliary body associated with massive intravitreal
      hemorrhage in an adult.

PMID- 18347645
TI  - Descemet membrane detachment following viscoelastic injection for
      posttrabeculectomy hypotony.

PMID- 18347648
TI  - Home parenteral nutrition in advanced cancer: where are we?
AB  - Patients with advanced and incurable cancer are a compelling group. Questions and
      comments that these individuals and their families have may include: "My daughter
      is expecting our first grandchild in 3 months--can I hope to see our new family
      member?"; "I can't keep any food down--is there anything I can do?"; "I am
      worried about losing so much weight, and feeling tired and weak--is there
      anything that may help?"; "Will I suffer a lot?". Indeed, the most pressing
      concerns of the patient relate to predictions about survival and control of
      symptoms. The clinician taking care of the patient may wonder what is the utility
      or futility of home parenteral nutrition (HPN) in both the individual with
      advanced cancer and in this population of patients at large, whether there is
      potential for harm such as increasing the burden of care or prolonging suffering,
      and how to optimize care and communication with the patient and their families.
      The nutrition scientist may want to know what the implications of advanced cancer
      are on nutrient requirements and utilization, whether there are markers that
      would differentiate between cachexia and simple starvation, and whether it is
      possible to use specific nutrients to modify the disease process. This review
      will provide insights into the understanding of the role of HPN in advanced
      cancer and opportunities for further investigation.

PMID- 18347649
TI  - Alcohol consumption: the good, the bad, and the indifferent.
AB  - Dietary ethanol (alcohol) is the most widely consumed drug worldwide. High levels
      of mortality, morbidity, and social malaise are associated with abuse of alcohol,
      and increasing numbers of women and youth are abusing alcohol. However, strong
      epidemiological data demonstrate a U- or J-shaped relationship between volume of
      alcohol consumed and all-cause mortality or disease burden. Moderate alcohol
      consumption is associated with a lower risk of all-cause mortality and disease
      burden than are abstinence and immoderate drinking. A brief review of the
      absorption, distribution, metabolism, and excretion of ethanol is provided with a
      discussion of the impact of gender differences. Potential mechanisms by which
      ethanol, ethanol metabolites, and (or) phytochemicals, as associated with
      different types of ethanol-containing beverages, are discussed in regards to the
      beneficial and detrimental impacts they may have on physiological system
      functioning and mortality or disease burden. Per capita consumption of ethanol
      containing beverages varies across geo-political regions worldwide. A more recent
      research focus is the impact of consumption patterns on consumption volumes as
      they relate to disease and mortality. Certain drinking patterns moderate overall
      volume of ethanol consumption. Thus, an emerging approach to the study of alcohol
      consumption in populations is to consider both the volume and pattern of
      consumption as they relate to mortality and disease burden. Alcohol consumption
      patterns among athletes are discussed; physiological implications of alcohol
      abuse in this population are outlined. Current guidelines for the consumption of
      alcohol are reviewed. Alcohol consumption guidelines reflect the current
      scientific understanding of both the benefits of moderate alcohol consumption and
      the detriments of immoderate alcohol consumption.

PMID- 18347650
TI  - Antioxidant supplemention in the treatment of skeletal muscle insulin resistance:
      potential mechanisms and clinical relevance.
AB  - The incidence of type 2 diabetes has increased dramatically over the past several
      decades and this trend is projected to continue into the foreseeable future.
      Skeletal muscle insulin resistance is thought to be a key development in the
      pathogenesis of type 2 diabetes. Given this fact, interventions that prevent or
      reverse impairments in skeletal muscle action can have profound effects on whole
      body glucose homeostasis. Traditional approaches used in this regard include
      exercise, weight loss, and insulin-sensitizing drugs such as thiazolidinediones
      (TZDs). Although these interventions have proven effective in improving glucose
      homeostasis, there are adherence issues seen with lifestyle interventions and
      undesirable side effects have been reported with TZDs. With these points in mind,
      the development of alternative strategies to maintain or improve skeletal muscle
      insulin sensitivity is warranted. In this context, the purpose of the present
      review is to highlight the role of antioxidant compounds in the prevention and
      treatment of skeletal muscle insulin resistance. Specifically, we will briefly
      describe the mechanisms of insulin-stimulated skeletal muscle glucose uptake and
      the potential mediators of oxidative stress induced insulin resistance, highlight
      data suggesting that antioxidant compounds can have beneficial effects on
      skeletal muscle insulin action, and discuss potential mechanisms mediating this
      effect.

PMID- 18347651
TI  - Central venous thrombosis in patients receiving long-term parenteral nutrition.
AB  - Long-term parenteral nutrition (PN) is administered to patients who are unable to
      use their gastrointestinal tract to absorb sufficient nutrients and water to
      maintain their nutritional status. Patients receiving long-term parenteral
      nutrition are at risk of numerous complications including thrombosis of the
      central venous catheter used to provide nutrition. Central venous access is
      essential to the successful delivery of long-term PN. One of the strategies to
      lessen the frequency of this complication is anticoagulation therapy with
      warfarin. The effect of warfarin in preventing this complication may be modified
      by vitamin K intake. Individuals with gastrointestinal failure may receive
      vitamin K from a variety of sources. This review summarizes the role of warfarin
      in preventing central venous access thrombosis. It also summarizes potential
      sources of vitamin K intake in home parenteral nutrition patients, examines the
      evidence for recommendations regarding vitamin K intake, and considers the
      potential impact of increased vitamin K intake on home PN patients, particularly
      on the prevention of central venous thrombosis.

PMID- 18347652
TI  - Effect of dietary protein content during recovery from high-intensity cycling on
      subsequent performance and markers of stress, inflammation, and muscle damage in
      well-trained men.
AB  - Nutrition is an important aspect of recuperation for athletes during multi-day
      competition or hard training. Post-exercise carbohydrate is likely to improve
      recovery, but the effect of protein is equivocal. The objective of this study was
      to determine the effect of post-exercise dietary protein content imposed over a
      high-carbohydrate background on subsequent performance. Using a crossover design,
      12 cyclists completed 3 high-intensity rides over 4 days. Day 1 comprised 2.5 h
      intervals, followed by repeat-sprint performance tests on days 2 (15 h post) and
      4 (60 h post), interspersed with a rest day. During 4 h recovery on days 1 and 2,
      cyclists ingested either 1.4 g.kg(-1).h(-1) carbohydrate, 0.7 g.kg(-1).h(-1)
      protein and 0.26 g.kg(-1).h(-1) fat (protein-enriched) or 2.1 g.kg(-1).h(-1)
      carbohydrate, 0.1 g.kg(-1).h(-1) protein, and equal fat (control). At other
      times, cyclists ingested a standardized high-carbohydrate diet. Anabolism was
      gauged indirectly by nitrogen balance, stress and inflammation via cortisol and
      cytokines, skeletal-muscle membrane disruption by creatine kinase, and oxidative
      stress by malonyl dealdehyde. Sprint mean power was not clearly different on day
      2 (0.0%; 95%CL: +/-3.9%), but on day 4 it was 4.1% higher (+/-4.1%) in the
      protein-enriched condition relative to control. Reduced creatine kinase was
      possible (26%; +/-30%) but effects on oxidative stress, inflammatory markers, and
      cortisol were inconclusive or trivial. Overnight nitrogen balance was positive in
      the protein-enriched condition on day 1 (249+/-70 mg N.kg FFM(-1); mean+/-SD),
      but negative (-48+/-26 mg N.kg FFM(-1)) in the control condition. A nutritive
      effect of post-exercise protein content was not discernible short term (15 h),
      but a delayed performance benefit (60 h) was observed following protein-enriched
      high-carbohydrate ingestion.

PMID- 18347653
TI  - Reliability of electromyographic and force measures during prone isometric back
      extension in subjects with and without low back pain.
AB  - Maximal voluntary isometric activations (MVIA) are frequently used as inputs for
      models attempting to predict muscle force and as normalization values in studies
      assessing muscle function. However, pain may adversely affect maximal muscle
      activation. The purpose of this study was to assess reliability of MVIA force and
      electromyographic (EMG) activity during prone isometric back extension in
      subjects with and without low back pain (LBP). A novel sub-maximal method using
      the percentages of the estimated mass of the head-arms-trunk (HAT) segment was
      also investigated. Repeated measures on 20 male volunteers divided into an LBP
      (n=10) and a control group (n=10) were made on 4 occasions. Force and EMG
      activity were recorded bilaterally from upper lumbar erector spinae (ULES), lower
      lumbar erector spinae (LLES), and biceps femoris (BF). Subjects exerted a maximal
      extension effort against a harness assembly that was attached to a force
      transducer. Submaximal exertions were also performed with an additional
      resistance of 100%, 110%, 120%, 130%, 140%, 150%, 160%, and 170% of HAT. Mean
      MVIA forces were significantly (p<or=0.05) lower in LBP vs. control. Intraclass
      correlation coefficients (ICC) for MVIA force, right and left ULES, and LLES EMG
      indicated high reliability in controls (R>0.90), but were significantly less in
      LBP (R=0.36-0.80). EMG of BF demonstrated excellent reliability across both
      groups (R>0.90). The resistance at 100% HAT demonstrated the highest reliability
      for LBP patients, whereas higher percentages of HAT showed either similar or
      higher reliability for controls. Force output and back EMG activity are less
      reliable with LBP individuals and should be taken into consideration when
      testing.

PMID- 18347654
TI  - Impact of metformin on peak aerobic capacity.
AB  - Individually, exercise and the drug metformin have been shown to prevent or delay
      type 2 diabetes. Metformin mildly inhibits complex I of the electron transport
      system and may impact aerobic capacity in people exercising while taking
      metformin. The purpose of the study was to evaluate the effects of metformin on
      maximal aerobic capacity in healthy individuals without mitochondrial
      dysfunction. Seventeen healthy, normal-weight men (n=11) and women (n=6)
      participated in a double-blind, placebo-controlled, cross-over design. Peak
      aerobic capacity was measured twice using a continuous, incrementally graded
      protocol; once after 7-9 d of metformin (final dose=2000 mg/d) and once with
      placebo, with 1 week between tests. The order of the conditions was
      counterbalanced. Peak oxygen uptake (VO2 peak), heart rate (HR), ventilation
      (VE), respiratory exchange ratio (RER), rating of perceived exertion (RPE), and
      test duration were compared across conditions using paired t tests with the R
      statistical program. VO2 peak (-2.7%), peak heart rate (-2.0%), peak ventilation
      (-6.2%), peak RER (-3.0%), and exercise duration (-4.1%) were all reduced
      slightly, but significantly, with metformin (all p<0.05). There was no effect of
      metformin on RPE or ventilatory breakpoint. Correlations between the decrement in
      VO2 peak and any of the other outcome variables were weak (r2<0.20) and not
      significant. Short-term treatment with metformin has statistically significant,
      but physiologically subtle, effects that reduce key outcomes related to maximal
      exercise capacity. Whether this small but consistent effect is manifested in
      people with insulin resistance or diabetes who already have some degree of
      mitochondrial dysfunction remains to be determined.

PMID- 18347655
TI  - Adjustment for gas exchange threshold enhances precision of heart rate-derived
      VO2 estimates during heavy exercise.
AB  - Overestimates of oxygen uptake (VO2) are derived from the heart rate reserve-VO2
      reserve (HRR-VO2R) model. We tested the hypothesis that adjusting for differences
      above and below gas exchange threshold (HRR-GET model) would tighten the
      precision of HR-derived VO2 estimates during heavy exercise. Seven men and 7
      women of various VO2 max levels, on 2 separate days, cycled for 6 min at
      intensities equal to power at GET, 15% the difference between GET and VO2 max
      (15% above), and at 30% above GET. A second bout at 15% above GET (15% above
      (bout 2)) after 3 min of recovery was performed to assess estimates during
      interval training. Actual VO2 was compared with estimates derived from the HRR
      VO2R and the HRR-GET. VO2 values were summed over the 6 min duration of data
      collection (6 min LO2) and compared with Bland-Altman plots. HRR-VO2R yielded 6
      min LO2 (+/-2 SD) overestimates of 2.0 (+/-2.5), 1.9 (+/-2.7), and 1.3 (+/-3.3)
      for GET, 15% over, and 30% over, respectively, whereas corresponding 6 min LO2
      difference values for the HRR-GET model were -0.42 (+/-1.6), -0.23 (+/-1.1), and 
      0.55 (+/-1.8), respectively. For 15% above (bout 2), the 6 min LO2 difference for
      HRR-VO2R was 1.8 (+/-2.9), whereas the difference for HRR-GET was 0.17 (+/-1.4).
      The 6 min LO2 values relative to the subjects' VO2 max did not vary (r=0.05 to
      0.36); therefore, fitness level did not affect estimates. Sex did not affect
      accuracy of either estimate model (sex X estimate model interaction, p>0.95). We
      observed accurate estimates from the HRR-GET model during heavy exercise.

PMID- 18347656
TI  - AMPK inactivation in mononuclear cells: a potential intracellular mechanism for
      exercise-induced immunosuppression.
AB  - There is much evidence that prolonged intense exercise suppresses the immune
      system. However, the intracellular biochemical mechanisms linking exercise and
      immunosuppression remain obscure. The purpose of this study was to investigate
      the hypothesis that exercise-induced inactivation of 5'AMP-activated protein
      kinase (AMPK) disrupts individual immune cell function, and thus may be linked to
      exercise-induced immunosuppression. To confirm AMPK's role in immune cells, AMPK
      activity was assessed in cultured monocytic Mono Mac 6 (MM6) cells. The effects
      of single bouts of intense exercise (45 min cycling; 70% VO2 max) on several
      immune parameters including mononuclear cell AMPK phosphorylation were
      investigated in 10 male volunteers. In vitro, the mitochondrial ATP synthase
      inhibitor oligomycin brought about transient decreases in cellular [ATP] (0.41+/
      0.04 pmol/cell to 0.31+/-0.02 pmol/cell), and activation of AMPKalpha1 (170.7%+/
      31.2% basal) and the glycolytic enzyme inducible phosphofructokinase 2 (iPFK-2)
      (225.0%+/-46.1% basal), with the latter effects coinciding with recovery from ATP
      depletion. In contrast, exercise-induced transient (approximately 1 h) decreases
      in AMPKalpha1 phosphorylation (64.4%+/-17.6% basal). This AMPK inactivation
      coincided with comparable transient decreases in other immune parameters
      (salivary IgA levels, serum cytokine levels, monocyte CD36 expression). Although
      the brief exercise bout employed here is not sufficient to cause full-fledged
      immunosuppression, exercise-induced transient decreases in mononuclear cell AMPK
      activation (as seen in this study) may cause energy depletion within individual
      immune cells, and therefore have an impact upon their ability to carry out their
      functions. Thus, we suggest that prolonged, repeated, high-intensity exercise
      that leads to clinically relevant immunosuppression may do so via AMPK
      inactivation within immune cells.

PMID- 18347657
TI  - Increase in depression symptoms with weight loss: association with glucose
      homeostasis and thyroid function.
AB  - The purpose of this study was to assess the potential impact of weight loss up to
      a state of plateau on symptoms of depression. Eleven obese men (mean body mass
      index (BMI)=33.4 kg.m(-2), mean age=38 y) participated in this repeated-measures,
      within-subjects, clinical intervention. They were subjected to a weight-loss
      program that consisted of a supervised diet and exercise clinical intervention.
      The phases investigated were (i) baseline; (ii) after 5+/-1 kg loss of body mass
      (phase 1); (iii) after 10+/-1 kg weight loss (phase 2); and (iv) at resistance to
      further weight loss (plateau). At each phase of the weight-reducing program,
      glucose homeostasis markers were determined using an oral glucose tolerance test
      (OGTT). Serum thyroid-stimulating hormone (TSH), total triiodothyronine (T3), and
      free thyroxine (fT4) concentrations were also measured and the Beck Depression
      Inventory (BDI) was administered. The weight loss plateau occurred after 7.4+/
      1.9 months of intervention and corresponded to a loss of 11.2% of initial body
      weight (93.9% of which was from fat stores). This amount of weight loss induced a
      significant decrease in resting metabolic rate (RMR) (p<0.05) and a significant
      increase in desire to eat (p<0.05) and in depression symptoms (p<0.01) compared
      with baseline. Intriguingly, the glucose area below fasting values (GABF) at
      plateau was significantly higher as compared with other phases of the program
      (p<0.01). We found a strong negative correlation (r=-0.77, p<0.01) between the
      change in glucose concentrations at 180 min of the OGTT and the change in BDI
      scores between plateau and baseline values. Similarly, highly significant
      relationships were found between the change in T3 or fT4 concentrations and the
      change in BDI scores (r=-0.71 and r=-0.68, respectively; p<0.01). Weight loss
      until plateauing is associated with a trend toward hypoglycemia at the end of the
      oral glucose challenge and with a decrease in T3 and fT4 levels. These
      physiological changes are shown to be highly linked with the increase in
      depression symptoms observed at plateau. Taken together, these data emphasize the
      relevance of caution and reasonable objectives when prescribing a weight
      reduction program to obese individuals.

PMID- 18347658
TI  - A chronic increase in physical activity inhibits fed-state mTOR/S6K1 signaling
      and reduces IRS-1 serine phosphorylation in rat skeletal muscle.
AB  - A chronic increase in physical activity and (or) endurance training can improve
      insulin sensitivity in insulin-resistant skeletal muscle. Cellular mechanisms
      responsible for the development of insulin resistance are unclear, though one
      proposed mechanism is that nutrient overload chronically increases available
      energy, over-activating the mammalian target of rapamycin (mTOR) and ribosomal S6
      kinase 1 (S6K1) signaling pathway leading to increased phosphorylation of serine
      residues on insulin receptor substrate-1 (IRS-1). The objective of this study was
      to determine if increased physical activity would inhibit mTOR/S6K1 signaling and
      reduce IRS-1 serine phosphorylation in rat skeletal muscle. Soleus muscle was
      collected from fed male Sprague-Dawley sedentary rats (Inactive) and rats with
      free access to running wheels for 9 weeks (Active). Immunoblotting methods were
      used to measure phosphorylation status of mTOR, S6K1, IRS-1, and PKB/Akt (protein
      kinase B/AKT), and total abundance of proteins associated with the mTOR pathway.
      Muscle citrate synthase activity and plasma insulin and glucose concentrations
      were measured. Phosphorylation of mTOR (Ser2448), S6K1 (Thr389), and IRS-1
      (Ser636-639) was reduced in Active rats (p<0.05). Total protein abundance of
      mTOR, S6K1, IRS-1, 4E-BP1, eEF2, PKB/Akt and AMPKalpha, and phosphorylation of
      PKB/Akt were unaffected (p>0.05). Total SKAR protein, a downstream target of
      S6K1, and citrate synthase activity increased in Active rats (p<0.05), though
      plasma insulin and glucose levels were unchanged (p>0.05). Reduced mTOR/S6K1
      signaling during chronic increases in physical activity may play an important
      regulatory role in the serine phosphorylation of IRS-1, which should be examined
      as a potential mechanism for attenuation of insulin resistance associated with
      increased IRS-1 serine phosphorylation.

PMID- 18347659
TI  - Use of parenteral nutrition in patients with advanced cancer.
AB  - The purpose of this study is to describe patient-related variables in a cohort of
      advanced cancer patients (ACPs) enrolled in a home parenteral nutrition (HPN)
      program. This study reviewed the cohort of ACPs enrolled in the Northern Alberta
      Home Total Parenteral Nutrition Program (NAHTPNP). Thirty-eight ACPs received HPN
      during the study period, 24% of all patients admitted for PN. Of these, 27 (71%)
      were female. Mean age was 48.76 y (SD 13.8 y). Bowel obstruction was the most
      common indication for initiating HPN (84%, 32) and ovarian cancer was the most
      common malignancy (34%, 13). Patients who began HPN with a Karnofsky performance
      status (KPS) of greater than 50 (median of 70) were found to have a longer
      duration of life (median: 6 months) compared with patients who began HPN with a
      KPS of 50 or below (median=50; median 3 months; p=0.01; two-tailed). There was no
      difference in survival between malignancy type (p=NS). Advanced cancer is the
      fastest growing indication for enrollment in the HPN program. ACP demonstrated a
      3% average annual increase proportionate to all indications for HPN starts,
      accounting for 7%-48% of HPN starts from 1999-2006. HPN is an increasingly used
      therapy for patients with advanced cancer, most commonly for intestinal failure
      in the setting of bowel obstruction. Initiation of HPN at a higher KPS was
      associated with a longer duration of life. Further studies are needed to validate
      the use of TPN in end-stage cancer patients.

PMID- 18347660
TI  - Influence of exercise intensity on pulmonary oxygen uptake kinetics at the onset
      of exercise and recovery in male adolescents.
AB  - The dynamics of the pulmonary oxygen uptake (VO2) responses to square-wave
      changes in work rate can provide insight into bioenergetic processes sustaining
      and limiting exercise performance. The dynamic responses at the onset of exercise
      and during recovery have been investigated systematically and are well
      characterized at all intensities in adults; however, they have not been
      investigated completely in adolescents. We investigated whether adolescents
      display a slow component in their VO2 on- and off-kinetic responses to heavy- and
      very heavy-intensity exercise, as demonstrated in adults. Healthy African
      American male adolescents (n=9, 14-17 years old) performed square-wave
      transitions on a cycle ergometer (from and to a baseline work rate of 20 W) to
      work rates of moderate (M), heavy (H), and very heavy (VH) intensity. In all
      subjects, the VO2 on-kinetics were best described with a single exponential at
      moderate intensity (tau1, on=36+/-11 s) and a double exponential at heavy (tau1,
      on=29+/-9 s; tau2, on=197+/-92 s) and very heavy (tau1, on=36+/-9 s; tau2,
      on=302+/-14 s) intensities. In contrast, the VO2 off-kinetics were best described
      with a single exponential at moderate (tau1, off=48+/-9 s) and heavy (tau1,
      off=53+/-7 s) intensities and a double exponential at very heavy (tau1, off=51+/
      3 s; tau2, off=471+/-54 s) intensity. In summary, adolescents consistently
      displayed a slow component during heavy exercise (on- but not off-transition) and
      very heavy exercise (on- and off-transitions). Although the overall response
      dynamics in adolescents were similar to those previously observed in adults,
      their specific characterizations were different, particularly the lack of
      symmetry between the on- and off-responses.

PMID- 18347661
TI  - Are functional foods redefining nutritional requirements?
AB  - Functional foods are increasing in popularity owing to their ability to confer
      health and physiological benefits. Nevertheless, the notion that functional foods
      improve health when providing nutrients at levels above and beyond existing
      recommended intakes is inconsistent with the definition of requirement. This
      disparity highlights the need for an alternative definition of nutrient
      requirement. The present objective is to examine distinctions between
      optimization of health, as defined by what we currently deem as required intakes,
      versus adding physiological benefit using bioactive agents found in functional
      foods. Presently, requirement is defined as the lowest amount of intake of a
      nutrient that will maintain a defined level of nourishment for a specific
      indicator of adequacy. In contrast, functional foods are described as ingredients
      that are not necessary for body function, yet provide added physiological benefit
      that confer better overall health. Plant sterols are one example of such an
      ingredient. Plant sterols lower plasma cholesterol concentrations, and may thus
      be considered essential nutrients in physiological situations where circulating
      cholesterol concentrations are high. Similarly, intakes of omega-3 fats beyond
      existing requirement may confer additional health benefits such as hypolipidemic
      and anti-diabetic effects. These examples underscore the inconsistencies between
      what is defined as a nutrient requirement versus what is identified as a health
      benefit of a functional food. Such discrepancies emphasize the need for a more
      all-encompassing definition of a nutrient requirement; that is, one that moves
      beyond the prevention of overt deficiency to encompass improved health and
      disease risk reduction.

PMID- 18347662
TI  - Muscling in on microarrays.
AB  - Adaptations that are the result of exercise require a multitude of changes at the
      level of gene expression. The mechanisms involved in regulating these changes are
      many, and can occur at various points in the pathways that affect gene
      expression. The completion of the human genome sequence, along with the genomes
      of related species, has provided an enormous amount of information to help
      dissect and understand these pathways. High-throughput methods, such as DNA
      microarrays, were the first on the scene to take advantage of this wealth of
      information. A new generation of microarrays has now taken the next step in
      revealing the mechanisms controlling gene expression. Analysis of the regulation
      of gene expression can now be profiled in a high-throughput fashion. However, the
      application of this technology has yet to be fully realized in the exercise
      physiology community. This review will highlight some of the latest advances in
      microarrays and briefly discuss some potential applications to the field of
      exercise physiology.

PMID- 18347663
TI  - Determinants of VO2 max decline with aging: an integrated perspective.
AB  - Aging is associated with a progressive decline in the capacity for physical
      activity. Central to this decline is a reduction in the maximal rate of oxygen
      utilization, or VO2 max. This critical perspective examines the roles played by
      the factors that determine the rate of muscle oxygen delivery versus those that
      determine the utilization of oxygen by muscle as a means of probing the reasons
      for VO2 max decline with aging. Reductions in muscle oxygen delivery, principally
      due to reduced cardiac output and perhaps also a maldistribution of cardiac
      output, appear to play the dominant role up until late middle age. On the other
      hand, there is a decline in skeletal muscle oxidative capacity with aging, due in
      part to mitochondrial dysfunction, which appears to play a particularly important
      role in extreme old age (senescence) where skeletal muscle VO2 max is observed to
      decline by approximately 50% even under conditions of similar oxygen delivery as
      young adult muscle. It is noteworthy that at least the structural aspects of the
      capillary bed do not appear to be reduced in a manner that would compromise the
      capacity for muscle oxygen diffusion even in senescence.

PMID- 18347666
TI  - Introduction to proceedings from the 2005 CSEP symposium "Exercise and the
      endothelium".
AB  - This introduction summarizes the topics addressed in the three companion review
      papers on various issues surrounding exercise and the endothelium. Leading
      experts in the field discuss the most recent findings regarding the following:
      (i) nitric oxide and exercise hyperemia, (ii) the response of the endothelium to
      exercise training, and (iii) the impact of exercise on the vascular biology of
      angiotensin as it relates to the vascular endothelium.

PMID- 18347667
TI  - Nitric oxide and muscle blood flow in exercise.
AB  - Despite being the subject of investigation for well over 100 years, the nature of
      exercising muscle blood flow control remains, in many respects, poorly
      understood. In this review we focus on the potential role of nitric oxide in
      vasodilation of muscle resistance vessels during a bout of exercise. Its
      contribution is explored in the context of whether it contributes to steady-state
      exercise hyperemia, the dynamic adjustment of muscle blood flow to exercise, or
      the modulation of sympathetic vasoconstriction in exercising muscle. It appears
      that the obligatory role of nitric oxide in all three of these categories is
      modest at best. The elucidation of the integrated nature of exercise hyperemia
      control in terms of synergy and redundancy of mechanism interaction remains in
      its infancy, and much more remains to be learned about the role of nitric oxide
      in this type of integrated control.

PMID- 18347668
TI  - Vascular biology of angiotensin and the impact of physical activity.
AB  - The renin-angiotensin system (RAS) is important for regulating blood pressure and
      extracellular fluid. The concept of the RAS has recently evolved from a classical
      systemic endocrine system to an appreciation of local RASs functioning in a
      paracrine manner, including in the vascular wall. Angiotensin II (AII), the main
      effector of the RAS, is a potent vasoconstrictor formed by the action of
      angiotensin-converting enzyme (ACE). ACE is multifunctional and also destroys the
      endogenous vasodilator bradykinin. A recently discovered novel ACE2 enzyme is
      responsible for forming a vasodilatory compound, angiotensin 1-7, from AII. Thus,
      the actions of ACE and ACE2 are antagonistic. Tissue actions of AII are mediated
      by specific receptors, AT1 and AT2, with AT1 mediating the classical actions. AT1
      stimulated vasoconstricton occurs via phospholipase-D-mediated second messenger
      generation directly, and indirectly via the coupling of AT1 to the prooxidant
      enzyme NADPH oxidase. Since the vascular NADPH oxidase is a major source of
      vascular reactive oxygen species generation and is responsible for the breakdown
      of the vasodilator nitric oxide (NO), there is another potential link between RAS
      and regulation of vasodilatory pathways. AT2 signaling is antagonistic to AT1
      signaling, and results in bradykinin and NO formation. Chronic AII signaling
      induces vascular dysfunction, whereas pharmacological management of the RAS can
      not only control blood pressure, but also correct endothelial dysfunction in
      hypertensives. Exercise training can also improve endothelial function in
      hypertensives, raising the question of whether there is a potential role for RAS
      in mediating the vascular effects of exercise training. Recent studies have
      demonstrated reductions in the expression of NADPH oxidase components in the
      vascular wall in response to exercise training, thus tempering one of the main
      cellular effectors of AII, and this is associated with reduced vascular ROS
      production and enhanced NO bioavailability. Importantly, it has now been
      demonstrated in human arteries that exercise training also tempers vascular AT1
      receptor expression and AII-induced vasoconstriction, while enhancing endothelium
      dependent dilation. The signals responsible for these chronic adaptations are not
      clearly understood, and may include changes in RAS components prompted by acute
      exercise. ACE genotype may have an effect on physical activity levels and on the
      cardiovascular responses to exercise training, and the II genotype (compared with
      ID and DD) is associated with the largest endothelium-dependent dilations in
      athletes compared with those in sedentary individuals. Thus, the tissue location
      of the RAS, the complement of ACE/ACE2, the receptor expression of AT1/AT2, and
      the ACE genotype are all variables that could impact the vascular responses to
      exercise training, but the responses of most of these variables to regular
      exercise training and the mechanisms responsible have not been systematically
      studied.

PMID- 18347669
TI  - Vascular nitric oxide: effects of exercise training in animals.
AB  - Exercise training is known to induce several adaptations in the cardiovascular
      system, one of which is increased skeletal muscle blood flow at maximal exercise.
      Improved muscle blood flow, in turn, could in part be accounted for by augmented
      endothelium-dependent, nitric oxide (NO)-mediated vasodilation. Studies have
      indeed demonstrated that endothelium-dependent, NO-mediated dilation of
      conductance-type vessels is augmented after endurance exercise training;
      recently, this adaptation has been extended into resistance-type vessels within
      rodent skeletal muscle. With the latter, however, it appears that only resistance
      vessels supplying muscle active during training sessions exhibit this adaptation.
      These findings in rats are in contrast to those from human studies, in which
      increased endothelium-dependent dilation has been observed in vasculatures not
      associated with elevated blood flow during exercise. Increased expression of
      endothelial NO synthase (eNOS) appears to underlie enhanced endothelium
      dependent, NO-mediated dilation of both conductance and resistance vessels.
      Greater eNOS expression may also underlie the preventive and (or) rehabilitative
      effect(s) of exercise training on atherosclerosis, given that NO inhibits several
      steps of the atherosclerotic disease process. Thus, exercise training may induce
      adaptations that benefit both vasodilation and vascular health.

PMID- 18347670
TI  - The impact of nutritional and exercise strategies for aging bone and muscle.
AB  - This symposium addressed recent evidence suggesting that nutritional intervention
      and resistance-training strategies may be important for aging bone and muscle.
      The physiological consequences of aging and the potential mechanistic actions of
      nutritional aids during resistance training were emphasized.

PMID- 18347671
TI  - Timing of creatine or protein supplementation and resistance training in the
      elderly.
AB  - Muscle loss with age has a negative effect on strength and functional
      independence. Age-related loss of muscle is the result of decreased muscle fiber
      number and size, which are functions of altered hormonal status, physical
      inactivity, and variations in nutritional intake. Resistance training has a
      positive effect on muscle mass and strength in the elderly. Studies of protein or
      creatine supplementation for increasing muscle mass and strength in older
      individuals are equivocal. The timing of nutritional supplementation may be more
      important than the absolute daily intake of supplements. Protein or creatine
      ingestion proximate to resistance-training sessions may be more beneficial for
      increasing muscle mass and strength than ingestion of protein or creatine at
      other times of the day, possibly because of increased blood flow and therefore
      increased transport of amino acids and creatine to skeletal muscle.

PMID- 18347672
TI  - Resistance training, sarcopenia, and the mitochondrial theory of aging.
AB  - Skeletal muscle aging is associated with a significant loss of muscle mass,
      strength, function, and quality of life. In addition, the healthcare cost of
      aging and age-related disease is growing, and will continue to grow as a larger
      proportion of our population reaches retirement age and beyond. The mitochondrial
      theory of aging has been identified as a leading explanation of the aging process
      and describes a path leading to cellular senescence that includes electron
      transport chain deficiency, reactive oxygen species production, and the
      accumulation of mitochondrial DNA deletions and mutations. It is also quite clear
      that regular resistance exercise is a potent and effective countermeasure for
      skeletal muscle aging. In this review, we discuss age-related sarcopenia, the
      mitochondrial theory of aging, and how resistance exercise may directly affect
      key components of the mitochondrial theory. It is clear from the data discussed
      that regular resistance training can effectively disturb processes that
      contribute to the progression of aging as it pertains to the mitochondrial
      theory.

PMID- 18347673
TI  - Effect of estrogenic compounds (estrogen or phytoestrogens) combined with
      exercise on bone and muscle mass in older individuals.
AB  - Exercise has a beneficial effect on bone, possibly by stimulating estrogen
      receptor alpha. Because estrogen up-regulates this receptor, estrogen therapy
      combined with exercise training may be optimal for increasing bone mineral
      density. Studies combining estrogen therapy and exercise training in
      postmenopausal women show mixed results, but indicate that the combination of
      interventions may be more effective for increasing bone mass than either
      intervention alone. Plant-like estrogens (i.e phytoestrogens such as soy
      isoflavones) may act as weak estrogen agonists or antagonists, have small
      beneficial effects on bone, and may interact with exercise for increasing bone
      mineral density. Phytoestrogen derived from flaxseed (flax lignans) has not been
      evaluated as extensively as soy isoflavones and thus its effect on bone is
      difficult to determine. Estrogen or soy isoflavones given to postmenopausal women
      results in a small increase in lean tissue mass that may be mediated through
      estrogen receptor alpha on muscle or through decreased inflammation.

PMID- 18347674
TI  - The potential benefits of creatine and conjugated linoleic acid as adjuncts to
      resistance training in older adults.
AB  - Human aging is associated with a significant reduction in muscle mass
      (sarcopenia) resulting in muscle weakness and functional limitations in the
      elderly. Sarcopenia has been associated with mitochondrial dysfunction and the
      accumulation of mtDNA deletions. Resistance training increases muscle strength
      and size and can increase mitochondrial capacity and decrease oxidative stress in
      older adults. Creatine monohydrate (CrM) and conjugated linoleic acid (CLA) have
      biological effects that could enhance some of the beneficial effects of
      resistance training in older adults (i.e., up arrow fat-free mass, down arrow
      total body fat). We have completed two resistance-training studies with CrM alone
      and CrM+CLA supplementation in older adults to evaluate the independent effects
      of exercise and dietary supplements, as well as their interactive effects. Our
      studies, and several others, have found that CrM enhanced the resistance exercise
      mediated gains in fat-free mass and strength. More recently, we found that the
      addition of CLA also lead to a significant reduction of body fat after six months
      of resistance training in older adults. Older adults have fewer wild-type mtDNA
      copies and higher amounts of mtDNA deletions as compared with younger adults in
      mature skeletal muscle; however, these deletions are not seen in the satellite
      cell-derived myoblast cultures. These findings, and the fact that mtDNA deletions
      are lower and wild-type mtDNA copy number is higher after resistance training in
      older adults, suggests that activation of satellite cells secondary to resistance
      exercise-induced muscle damage can dilute or "shift" the proportion of mtDNA
      genotype towards that of a younger adult. Recent evidence suggests that CrM
      supplementation in combination with strength training can enhance satellite cell
      activation and total myonuclei number per muscle fiber in young men. Future
      studies are required to determine whether the mitochondrial adaptations to
      resistance exercise in older adults are further enhanced with CrM supplementation
      and whether this is due to increased recruitment of satellite cells. It will also
      be important to determine whether these changes are maintained over a longer time
      period.

PMID- 18347677
TI  - Muscle deoxygenation of upper-limb muscles during progressive arm-cranking
      exercise.
AB  - The purpose of this study was to determine which upper-limb muscle exhibits the
      greatest change in muscle deoxygenation during arm-cranking exercise (ACE). We
      hypothesized that the biceps brachii (BB) would show the greatest change in
      muscle deoxygenation during progressive ACE to exhaustion relative to triceps
      brachii (TR), brachioradialis (BR), and anterior deltoid (AD). Healthy young men
      (n = 11; age = 27 +/- 1 y; mean +/- SEM) performed an incremental ACE test to
      exhaustion. Near-infrared spectroscopy (NIRS) was used to monitor the relative
      concentration changes in oxy- (O2Hb), deoxy- (HHb), and total hemoglobin (Hbtot),
      as well as tissue oxygenation index (TOI) in each of the 4 muscles. During
      submaximal arm exercise, we found that changes to NIRS-derived measurements were
      not different between the 4 muscles studied (p > 0.05). At maximal exercise HHb
      was significantly higher in the BB compared with AD (p < 0.05). Relative to the
      other 3 muscles, BB exhibited the greatest decrease in O2Hb and TOI (p < 0.05).
      Our investigation provides two new and important findings: (i) during submaximal
      ACE the BB, TR, BR, and AD exhibit similar changes in muscle deoxygenation and
      (ii) during maximal ACE the BB exhibits the greatest change in intramuscular O2
      status.

PMID- 18347678
TI  - Association between dietary fat intake, liver fat, and insulin sensitivity in
      sedentary, abdominally obese, older men.
AB  - Whether dietary fat influences the interaction between liver fat, visceral
      adipose tissue (VAT), and metabolic risk is unclear. Thus, we sought to determine
      the independent associations between 1 and 10 d dietary fat intake, liver fat,
      and VAT on insulin sensitivity using a cross-sectional design. Liver fat score
      (LFS) was assessed by computed tomography and VAT by magnetic resonance imaging
      in 42 abdominally obese older men. Insulin sensitivity was measured by the
      hyperinsulinemic-euglycemic clamp technique. Diet composition was determined from
      self-recorded diet records for 1 and 10 d preceding the assessment of LFS. LFS
      was positively associated with the 10 d average fat and alcohol intake, but not
      with any 1 d average dietary variables. VAT (r = -0.36) and LFS (r = -0.32) were
      both negatively correlated with insulin sensitivity (p < 0.05). When LFS and VAT
      were entered in the same model, only VAT was an independent predictor of insulin
      sensitivity (p < 0.05). Control for the average 10 d alcohol consumption and fat
      intake improved the association between insulin sensitivity and LFS (from r = 
      0.32, p > 0.10 to r = -0.49, p < 0.05), but not VAT. In fact, after control for
      the 10 d dietary variables, both LFS and VAT were independent predictors of
      insulin sensitivity (p < 0.05). This was not true for any of the 1 d dietary
      intake variables. In conclusion, liver fat is associated with dietary fat intake
      and alcohol consumption over 10 d, but not 1 d. Furthermore, dietary habits may
      influence the relationship between liver fat and insulin sensitivity.

PMID- 18347679
TI  - Post-exercise hypotension and cardiovascular responses to moderate orthostatic
      stress in endurance-trained males.
AB  - We tested the hypothesis that following an acute bout of exercise cardiovascular
      and cerebrovascular responses to lower-body negative pressure (LBNP) would be
      altered due to post-exercise hypotension (PEH). Ten healthy, male, endurance
      trained athletes (mean age +/- SD = 29.6 +/- 5) were assessed for cardiovascular
      and cerebrovascular responses to LBNP following acute bouts of interval and
      continuous exercise. Mean arterial pressure (MAP), cardiac output, total
      peripheral resistance, heart rate variability, and total cerebral oxygen index
      were determined during a baseline LBNP session. These indices were also
      determined during two other LBNP sessions: following an acute bout of interval
      exercise, and following an acute bout of continuous exercise. Compared with
      baseline, MAP was reduced after both exercise conditions, similar to values
      previously reported (10 mmHg; p < 0.05 vs. pre-exercise). Total peripheral
      resistance was significantly reduced following both exercise bouts, and heart
      rate was significantly increased post-exercise (rest: 59.6 +/- 11.2; interval:
      77.8 +/- 12.8; continuous: 80.3 +/- 15.2 beats.min(-1)). Both cardiac output and
      stroke volume responses to LBNP following exercise were not altered when compared
      with baseline measurements. Tissue oxygenation during -40 mmHg (interval: 74.31%
      +/- 7.82% vs. continuous: 69.13% +/- 5.23%) was significantly lower than during
      normobaric pressure (interval: 77.14% +/- 1.30% vs. continuous: 74.41% +/-
      0.94%). It appears from these observations that although young, endurance-trained
      males experience PEH following acute bouts of interval or continuous exercise,
      this hypotension does not alter the cardiovascular and cerebrovascular responses
      to a moderate orthostatic stress.

PMID- 18347680
TI  - Chronic quercetin ingestion and exercise-induced oxidative damage and
      inflammation.
AB  - Quercetin is a flavonoid compound that has been demonstrated to be a potent
      antioxidant in vitro. The objective of this study was to evaluate if quercetin
      ingestion would increase plasma antioxidant measures and attenuate increases in
      exercise-induced oxidative damage. Forty athletes were recruited and randomized
      to quercetin or placebo. Subjects consumed 1000 mg quercetin or placebo each day
      for 6 weeks before and during 3 d of cycling at 57% work maximum for 3 h. Blood
      was collected before and immediately after exercise each day, and analyzed for F2
      isoprostanes, nitrite, ferric-reducing ability of plasma, trolox equivalent
      antioxidant capacity, and C-reactive protein. Statistical analyses involved a 2
      (treatment) x 6 (times) repeated measures analysis of variance to test main
      effects. F2-isoprostanes, nitrite, ferric-reducing ability of plasma, trolox
      equivalent antioxidant capacity, and C-reactive protein were significantly
      elevated as a result of exercise, but no group effects were found. Despite
      previous data demonstrating potent antioxidant actions of quercetin in vitro,
      this study indicates that this effect is absent in vivo and that chronic
      quercetin ingestion does not exert protection from exercise-induced oxidative
      stress and inflammation.

PMID- 18347681
TI  - Sweat rate, salt loss, and fluid intake during an intense on-ice practice in
      elite Canadian male junior hockey players.
AB  - Previous research in many sports suggests that losing ~1%-2% body mass through
      sweating impairs athletic performance. Elite-level hockey involves high-intensity
      bursts of skating, arena temperatures are >10 degrees C, and players wear
      protective equipment, all of which promote sweating. This study examined the pre
      practice hydration, on-ice fluid intake, and sweat and sodium losses of 44
      candidates for Canada's junior men's hockey team (mean +/- SE age, 18.4 +/- 0.1
      y; height, 184.8 +/- 0.9 cm; mass, 89.9 +/- 1.1 kg). Players were studied in
      groups of 10-12 during 4 intense 1 h practices (13.9 degrees C, 66% relative
      humidity) on 1 day. Hydration status was estimated by measuring urine specific
      gravity (USG). Sweat rate was calculated from body mass changes and fluid intake.
      Sweat sodium concentration ([Na]) was analyzed in forehead sweat patch samples
      and used with sweat rate to estimate sodium loss. Over 50% of players began
      practice mildly hypohydrated (USG > 1.020). Sweat rate during practice was 1.8 +/
      0.1 L.h(-1) and players replaced 58% (1.0 +/- 0.1 L.h(-1)) of the sweat lost.
      Body mass loss averaged 0.8% +/- 0.1%, but 1/3 of players lost more than 1%.
      Sweat [Na] was 54.2 +/- 2.4 mmol.L(-1) and sodium loss averaged 2.26 +/- 0.17 g
      during practice. Players drank only water during practice and replaced no sodium.
      In summary, elite junior hockey players incurred large sweat and sodium losses
      during an intense practice, but 2/3 of players drank enough to minimize body mass
      loss. However, 1/3 of players lost more than 1% body mass despite ready access to
      fluid and numerous drinking opportunities from the coaches.

PMID- 18347682
TI  - Influence of fiber-type composition on recovery from tourniquet-induced skeletal
      muscle ischemia-reperfusion injury.
AB  - This study was designed to determine if previously reported differences in the
      functional impairment of muscles composed of predominantly different fiber types
      occurs following extended periods of ischemia. We hypothesized that the soleus
      (Sol) muscle, a predominantly slow-twitch muscle, would be less vulnerable to
      tourniquet-induced ischemia-reperfusion than the plantaris (Plant), a
      predominantly fast-twitch muscle, as determined by the assessment of isometric
      contractile function. Male Sprague-Dawley rats were assigned to one of the
      following groups to undergo tourniquet application (TKA) (n = 6/group): 2 h TKA,
      2 d recovery; 4 h TKA, 2 d recovery; 2 h TKA, 14 d recovery; or 4 h TKA, 14 d
      recovery. In situ isometric contractile properties were assessed in the
      predominantly slow-twitch Sol and the predominantly fast-twitch Plant; the
      contralateral muscle served as the internal control. At 2 d, muscle contraction
      could not be elicited via neural stimulation, but muscles did contract with
      direct stimulation, which indicates neural injury. This condition was resolved by
      day 14. At this time point, tetanic tension (Po) in the Plant was reduced by 45%
      and 69% in the 2 and 4 h groups, respectively. Po for the Sol was unaffected in
      the 2 h group, but was reduced by 30% in the 4 h group. The fatigue resistance of
      the Plant was increased 2 fold in the 4 h group and was unchanged in all other
      groups. These results demonstrate that vulnerability to tourniquet-induced
      ischemia-reperfusion injury is dramatically different with respect to muscle
      fiber-type composition.

PMID- 18347683
TI  - Plasma lipoprotein (a), homocysteine, and other cardiovascular disease (CVD) risk
      factors in Nigerians with CVD.
AB  - Elevated plasma lipoprotein (a) (Lp(a)) and total homocysteine (tHcy)
      concentrations, as well as fat distributions, are associated with cardiovascular
      disease (CVD) risk. The purpose of this study was to evaluate plasma Lp(a), tHcy,
      percentage body fat, anthropometric indices, and blood pressure (BP) and their
      relationships with each other in well-defined, hospital-based, CVD patients in a
      Nigerian African community. One hundred seventy patients suffering from
      hypertensive heart disease, hypertension, ischaemic heart disease, and myocardial
      infraction with the mean age of 45.3 +/- 1.3 years and 58 apparently healthy
      volunteers with the mean age of 44.8 +/-1.2 years were selected. Anthropometric
      indices and BP were measured. Percentage body fat, body mass index, and waist-to
      hip ratio (WHR) were calculated. Plasma Lp(a) and tHcy concentrations were
      determined. The results showed significant increases in BP, skinfold thickness
      (SFT) variables, and WHR in all of the CVD patients. Plasma Lp(a) was also
      significantly increased (p < 0.001), whereas the slight increase in the mean tHcy
      was not statistically significant. Positive significant correlations were found
      between systolic BP, triceps, SFT, and percentage body fat (p < 0.01), whereas
      significant correlations were found between some body composition variables,
      tHcy, and systolic BP (p < 0.05). Our findings provide supportive evidence for
      altered plasma Lp(a) concentration in addition to some other traditional CVD risk
      factors in Nigerians. The role of homocysteine is not well defined.

PMID- 18347684
TI  - Anaerobic performance when rehydrating with water or commercially available
      sports drinks during prolonged exercise in the heat.
AB  - The effects that rehydrating drinks ingested during exercise may have on
      anaerobic exercise performance are unclear. This study aimed to determine which
      of four commercial rehydrating drinks better maintains leg power and force during
      prolonged cycling in the heat. Seven endurance-trained and heat-acclimatized
      cyclists pedaled for 120 min at 63% maximum oxygen consumption in a hot, dry
      environment (36 degrees C; 29% humidity, 1.9 m.s-1 airflow). In five randomized
      trials, during exercise, subjects drank 2.4 +/- 0.1 L of (i) mineral water (WAT;
      San Benedetto), (ii) 6% carbohydrate-electrolyte solution (Gatorade lemon), (iii)
      8% carbohydrate-electrolyte solution (Powerade Citrus Charge), (iv) 8%
      carbohydrate-electrolyte solution with lower sodium concentration than other
      sports drinks (Aquarius orange), or (v) did not ingest any fluid (DEH). Fluid
      balance, rectal temperature (Trec), maximal cycling power (Pmax), and leg maximal
      voluntary isometric contraction (MVC) were measured. During DEH, subjects lost
      3.7 +/- 0.2% of initial body mass, whereas subjects lost only 0.8% +/- 0.1% in
      the other trials (p < 0.05). Final Trec was higher in DEH than in the rest of the
      trials (39.4 +/- 0.1 degrees C vs. 38.7 +/- 0.1 degrees C; p < 0.05). Pmax was
      similar among all trials. Gatorade and Powerade preserved MVC better than DEH (
      3.1% +/- 2% and -3.8% +/- 2% vs. -11% +/- 2%, p < 0.05), respectively, whereas
      WAT and Aquarius did not (-6% +/- 2%). Compared with DEH, rehydration with
      commercially available sports drinks during prolonged exercise in the heat
      preserves leg force, whereas rehydrating with water does not. However, low sodium
      concentration in a sports drink seems to preclude its ergogenic effects on force.

PMID- 18347685
TI  - The time course of denervation-induced changes is similar in soleus muscles of
      adult and old rats.
AB  - Muscle denervation is accompanied by atrophy and a decline in oxidative capacity.
      We investigated whether the time course of adaptations following denervation of
      the soleus muscle differs in adult (5 months old) and older adult (25 months old)
      rats. We denervated the soleus muscle of the left leg, while the right leg served
      as an internal control. Two weeks after denervation, muscle mass was decreased
      both in adult and old animals to, respectively, 57% and 54% (p < 0.001) and
      capillary to fibre ratio (C:F) decreased to 51% and 50% (p < 0.01) of the control
      values. Yet, the capillary density was increased in older adult but not in adult
      muscles, indicating that the regression of the capillary bed during denervation
      lags behind the decrease in fibre size in the soleus muscle of the older rats.
      One week after denervation the optical density of sections stained for succinate
      dehydrogenase was 83% and 79% (p < 0.05) of control adult and older adult
      muscles, respectively, and then remained stable. This indicates that during the
      first week of denervation loss of oxidative capacity occurred at a relatively
      higher rate than that of muscle mass. No major changes occurred between 2 and 4
      weeks of denervation, except for an increase in the proportion of hybrid (I/IIa)
      fibres in 4 week denervated muscles (adult 10% vs. 23%; old 1% vs. 13%; p <
      0.05). Except for changes in capillarisation, the time course of atrophy and
      decrease in oxidative capacity following denervation was similar in soleus
      muscles from adult and old rats.

PMID- 18347686
TI  - Relationship between the metabolic syndrome and physical activity energy
      expenditure: a MONET study.
AB  - The purpose of this cross-sectional study was to examine the association between
      the metabolic syndrome (MetS) and physical activity energy expenditure (PAEE) in
      overweight and obese sedentary postmenopausal women. The study population
      consisted of 137 overweight and obese sedentary postmenopausal women (age, 57.7
      +/- 4.8 years; BMI, 32.4 +/- 4.6 kg.m(-2)). Subjects had the MetS if 3 out of the
      following 5 criteria were met: visceral fat > 130 cm2, high-density lipoprotein
      (HDL) cholesterol < 1.29 mmol.L(-1), fasting triglycerides > or = 1.7 mmol.L(-1),
      blood pressure > or = 130/85 mmHg, and fasting glucose > or =5.6 mmol.L(-1). We
      measured (i) body composition (by dual-energy X-ray absorptiometry); (ii)
      visceral fat (by computed tomography); (iii) insulin sensitivity (using the
      hyperinsulinemic-euglycemic clamp); (iv) plasma lipids, fasting glucose, and
      insulin, as well as 2 h glucose during an oral glucose tolerance test; (v)
      resting blood pressure; (vi) peak oxygen consumption (VO2 peak); (vii) PAEE
      (using doubly labeled water); and (viii) lower-body muscle strength (using weight
      training equipment). Forty-two women (30.7%) had the MetS in our cohort.
      Individuals without the MetS had significantly higher levels of PAEE (962 +/- 296
      vs. 837 +/- 271 kcal.d(-1); p < 0.05), VO2 peak (18.2 +/- 3.0 vs. 16.7 +/- 3.2
      mL.min(-1).kg(-1); p < 0.05), and insulin sensitivity, as well as significantly
      lower levels of 2 h glucose and central lean body mass. No differences in total
      energy expenditure, resting metabolic rate, and muscle strength between groups
      were observed. Logistic regression analysis showed that 2 h glucose (odds ratio
      (OR): 1.50 (95% CI 1.17-1.92)), central lean body mass (OR: 1.17 (95% CI 1.05
      1.31)), and PAEE (OR: 0.998 (95% CI 0.997-1.000)), but not VO2 peak and (or)
      muscle strength, were independent predictors of the MetS. Lower levels of PAEE
      and higher levels of 2 h glucose, as well as central lean body mass, are
      independent determinants of the MetS in our cohort of overweight and obese
      postmenopausal women.

PMID- 18347687
TI  - Adding carbohydrate to a high-fat meal blunts postprandial lipemia in women and
      reduces meal-derived fatty acids in systemic circulation.
AB  - The lipemic response to a meal is an important independent risk factor for the
      development of cardiovascular disease. The purpose of this study was to determine
      the effect of adding carbohydrate (CHO) to a fat meal on the bioavailability of
      ingested fat in different blood lipid fractions in men and women. On two separate
      occasions, 18 healthy adults (9 women, 9 men) ate either a high-fat meal (0.7
      grams fat per kilogram) (FAT), or the same meal with added CHO (1 gram CHO per
      kilogram) (FAT+CHO) in the morning after a 12 h fast. Both meals were
      supplemented with [13C]-palmitate (25 mg.kg(-1)). Plasma concentrations of
      triglyceride (TG), fatty acids, insulin, and glucose were measured in blood
      samples taken hourly from 0 to 8 h after the meal. In addition, we measured TG
      concentrations in chylomicron (CHYLO-TG) and in very-low-density lipoprotein
      (VLDL-TG) fractions. The addition of CHO to the fat meal increased plasma glucose
      and insulin concentrations identically in men and women. In contrast, adding CHO
      to the fat meal reduced the plasma TG concentration in the 5 h after the meal in
      women (average 5 h [TG]: 1.27 +/- 0.11 and 1.01 +/- 0.09 mmol.L(-1); p <0.05),
      but not in men (1.25 +/- 0.23 and 1.24 +/- 0.20 mmol.L(-1)). Despite differences
      in the lipemic response to the meals between men and women, we found that adding
      carbohydrate to a fat meal decreased the bioavailability of meal-derived [13C]
      palmitate in the systemic fatty acid pool, and decreased the incorporation of
      [13C]-palmitate into VLDL-TG in both men and women. In summary, adding CHO to a
      fat meal markedly blunted the plasma TG response in women, but not in men, which
      may augment the atherogenic potential after each meal in men.

PMID- 18347688
TI  - Reproducibility of short-term food intake and subjective appetite scores after a
      glucose preload, ventilation threshold, and body composition in boys.
AB  - The objective of these studies was to assess the reproducibility of (i) short
      term food intake (FI) and subjective appetite following a glucose preload, (ii)
      ventilation threshold (VT) and subjective appetite after short-duration exercise,
      and (iii) body composition assessed by bioelectrical impedance (BIA). On two
      separate weekend mornings, boys (n = 11; aged 9-14 years) received drinks
      containing 50 g glucose made up to 250 mL with water 2 h after a standardized
      breakfast. FI from a pizza meal was measured 30 min later. Subjective appetite
      was measured before and after the glucose loads and the VT measures. VTs were
      measured on 2 weekday evenings, 1 week apart. BIA was measured during the FI
      assessment sessions. Short-term FI after the glucose preload was highly
      reproducible. Mean energy intake was 925 +/- 139 kcal on the first day and 988 +/
      147 kcal on the second day (coefficient of repeatability (CR) = 259 kcal; intra
      class correlation coefficient (ICC) = 0.96). Moderate reproducibility of the
      average appetite score was found at 30 min (CR = 24 mm; ICC = 0.82). Subjective
      appetite was increased similarly by short-duration exercise on both days (CR = 19
      mm). Absolute VT was more highly reproducible (CR = 359 mL O2.min(-1), ICC =
      0.85) than VT expressed on the basis of body weight (CR = 8.0 mL O2.kg(-1).min(
      1), ICC = 0.59). Fat mass (FM) estimated from BIA was highly reproducible (CR =
      2.7 kg, ICC = 0.95), but underestimated FM compared with skinfolds. In
      conclusion, FI and subjective appetite scores in response to glucose preloads,
      VT, subjective appetite after short-duration exercise, and estimates of FM from
      BIA are reproducible in boys.

PMID- 18347689
TI  - Parents report intrapersonal, interpersonal, and environmental barriers to
      supporting healthy eating and physical activity among their preschoolers.
AB  - There is an increasing trend in childhood obesity in Canada and many preschool
      children are overweight or obese. The objective of this study was to explore
      parents' experiences and challenges in supporting healthy eating and physical
      activity among their preschool children. A qualitative descriptive study
      involving 5 focus groups was conducted. A convenience sample of 39 parents from 3
      childcare centres in Hamilton, Ontario, participated. Parents were English
      speaking and had a child aged 2-5 years attending the childcare centre for at
      least 3 months. The research team read transcripts of the audio-taped sessions
      and used a constant comparison approach to develop themes, which involved coding
      comments by continually referring to previously coded comments for comparison.
      The social ecological model was used to organize the themes into 3 higher-level
      categories: (i) intrapersonal (individual): preschoolers' preferences and health;
      (ii) interpersonal (interactions): parents' and others' different views and
      practices, influence of the childcare centre, parents' lack of time, and family
      structure; and (iii) physical environment: accessibility of healthy foods,
      preschoolers with special needs, media influence, weather, lack of safety, and
      inaccessible resources. Parents perceived that there are various intrapersonal,
      interpersonal, and environmental barriers to supporting healthy eating and
      physical activity among their children. Program planners and health professionals
      can consider these barriers when developing interventions to promote healthy
      bodyweights among preschoolers.

PMID- 18347690
TI  - Correlation between the rate of weight loss and changes in body composition in
      obese postmenopausal women after 5 weeks: a pilot study.
AB  - Approximately 25% of weight lost during restrictive diets (without exercise) is
      lean body mass (LBM). No study has yet investigated the impact of the rate of
      weight loss (RWL) on LBM and fat mass (FM). The purpose of this study was to
      investigate the relationships between the RWL and body composition in older obese
      women. Twenty obese postmenopausal women aged between 51 and 74 years enrolled in
      a 5 week dietary weight loss intervention. Subjects were characterized according
      to their RWL (low RWL < 0.74 kg.week(-1) (n = 9) vs. high RWL > or = 0.74
      kg.week(-1) (n = 11)). Total and trunk FM and LBM (by dual-energy X-ray
      absorptiometry) were measured before and after weight loss. A significant
      correlation was observed between the RWL (kg.week(-1)) and changes in LBM
      (kg.week(-1)) (r = 0.75; p = 0.0002). However, no association was observed with
      changes in FM (kg.week(-1)) (r = 0.40; p = 0.08). Both groups showed a similar
      decrease in FM (low RWL, -2.7 +/- 0.9 kg,; high RWL, -3.2 +/- 0.8 kg; p = 0.38),
      whereas losses in LBM were significantly higher in the high RWL than in the low
      RWL group (-1.6 +/- 1.2 kg vs. -0.4 +/- 1.1 kg; p = 0.05). An RWL > 0.74 kg.week(
      1) was associated with a greater loss of LBM, but had no extra benefits on FM
      after a 5 week weight loss program. Current guidelines, which recommend RWL up to
      0.91 kg.week(-1), might not be optimal to prevent decreases in LBM in
      postmenopausal women when no exercise is added.

PMID- 18347691
TI  - Metabolic syndrome in three ethnic groups using current definitions.
AB  - According to two current definitions, the prevalence of the metabolic syndrome
      (MetS) among black Haitians of Montreal was <20%, 30%-36% in Algonquin Indians of
      Quebec, and >45% in Mexicans of Oaxaca (all aged 35-60 y). Although phenotypes
      were different, high triglycerides and fasting dysglycemia were good predictors
      of MetS in all three groups using both definitions. The international cut-offs
      for abdominal obesity were not predictive of MetS in the Haitian subjects.

PMID- 18347694
TI  - Expert panel report from the International Conference on Physical Activity and
      Obesity in Children, 24-27 June 2007, Toronto, Ontario: summary statement and
      recommendations.
AB  - The increasing prevalence of obesity among the world's children and youth was the
      impetus for an international conference convened in Toronto, Canada, to examine
      issues related to physical activity and obesity in children (24-27 June 2007).
      The goal of the conference was to assimilate, interpret, and share scientific
      evidence with key stakeholders to develop recommendations concerning effective
      physical activity policies and programs to address obesity in children. The
      conference was attended by approximately 1,000 delegates from 33 countries who
      gathered to listen to the invited speakers and to share information on promising
      practices related to the promotion of physical activity with the aim of reducing
      the burden of obesity in children. The major topics addressed at the conference
      included the biological and behavioural causes of obesity, current and past
      levels of physical activity and sedentarism in children, the role of the social,
      family, and built environments in addressing the physical activity deficit, and
      the role of legislation and industry in promoting physical activity. Promising
      physical activity interventions among children were presented, and important
      research, policy, and practice recommendations to address the issue of physical
      inactivity and obesity were provided.

PMID- 18347695
TI  - 2006 CSEP Annual Scientific Conference, Halifax, Nova Scotia, 1-4 November 2006.
      Pediatric exercise physiology symposium: a tribute to Oded Bar-Or. Introduction.
AB  - Dr. Oded Bar-Or was a pioneer in the study of children's physical activity,
      exercise, and health. His diverse research interests led to numerous scientific
      explorations on thermoregulation, aerobic and anaerobic capacity, physical
      activity, economy of movement, obesity, neuromuscular diseases, asthma, cystic
      fibrosis (CF), and many more. To commemorate the extraordinary contributions that
      Dr. Bar-Or made to the study of exercise and youth, a symposium on pediatric
      exercise physiology was held at the CSEP's 2006 Annual Meeting in Halifax. The
      papers in the following pages include the four papers presented by international
      colleagues in his memory.

PMID- 18347696
TI  - Acute physical activity and sports injuries in children.
AB  - An increase in the physical activity of individuals has many health benefits, but
      a drawback of an increase in physical activity is the risk of related injuries.
      To reduce the short- and long-term effects in terms of social and economic
      consequences, prevention of physical activity injuries is an important challenge.
      A sequence of prevention model has been proposed that aims to prevent physical
      activity injuries in different steps. The model includes (i) identification of
      the problem in terms of incidence and severity of physical activity injuries,
      (ii) identification of the risk factors and injury mechanisms that play a role in
      the occurrence of physical activity injuries, (iii) introduction of measures that
      are likely to reduce the future risk and (or) severity of physical activity
      injuries, and (iv) evaluation of the effectiveness of the measures by conducting
      a randomized controlled trial (RCT). This review describes what is currently
      known about all of the various aspects of the sequence of prevention in children
      (steps i-iv).

PMID- 18347697
TI  - Non-invasive methods in paediatric exercise physiology.
AB  - Oded Bar-Or's hypothesis that children may be "metabolic non-specialists", even
      when engaging in specialized sports, has stimulated the study of paediatric
      exercise metabolism since the publication of his classic text Pediatric sports
      medicine for the practitioner in 1983. Evidence drawn from several methodologies
      indicates an interplay of anaerobic and aerobic exercise metabolism in which
      children have a relatively higher metabolic contribution from oxidative energy
      pathways than adolescents or adults, whereas there is a progressive increase in
      glycolytic support of exercise with age, at least into adolescence and possibly
      into young adulthood. The picture is generally consistent but incomplete, as
      research with young people has been limited by both ethical and methodological
      constraints. The recent rigorous introduction of non-invasive techniques such as
      breath-by-breath respiratory gas analysis and magnetic resonance spectroscopy
      into paediatric exercise physiology promises to open up new avenues of research
      and generate unique insights into the metabolism of the exercising muscle during
      growth and maturation. It therefore appears that we might have available the
      tools necessary to answer some of the elegant questions raised by Professor Bar
      Or over 25 years ago.

PMID- 18347698
TI  - A pediatric perspective on inflammation and oxidative stress in response to
      exercise.
AB  - Dr. Oded Bar-Or was a giant in the area of pediatric exercise science and made
      numerous contributions to the health of children around the world. He also had a
      significant impact on a relatively new area of pediatric exercise science --
      pediatric exercise immunology. Under his supervision, some aspects of the
      immunobiology of exercise have been unravelled from a pediatric perspective. In
      general, healthy children experience less inflammatory stress in response to
      standardized exercise, while demonstrating an exercise-induced elevation in the
      anabolic cytokine IL-8. Mechanisms for the maturity- and age-dependent changes in
      cytokine responses to exercise are unknown, but may involve oxidative stress.
      Studies of oxidative stress and exercise in children are scant, but preliminary
      data suggests that, like the inflammatory cytokine response to exercise, children
      may experience less oxidative stress in response to intense exercise. We propose
      that the links between exercise, inflammatory and oxidative stress, and growth
      factors will be important to understand in the context of how exercise
      contributes to optimal growth and development during childhood. This
      understanding will be particularly relevant for childhood diseases that restrict
      growth.

PMID- 18347699
TI  - Children's thermoregulation during exercise in the heat: a revisit.
AB  - The review revisits some child-adult differences relevant to thermoregulation and
      offers alternatives to accepted interpretations. Morphologically, children have a
      higher body surface area to mass ratio -- a major factor in "dry" heat
      dissipation and effective sweat evaporation. Locomotion-wise, children are less
      economical than adults, producing more heat per unit body mass. Additionally,
      children need to divert a greater proportion of their cardiac output to the skin
      under heat stress. Thus, a larger proportion of their cardiac output is shunted
      away from the body's core and working muscles -- particularly in hot conditions.
      Finally, under all environmental conditions and allometric comparisons,
      children's sweating rates are lower than those of adults. The differences appear
      to suggest thermoregulatory inferiority, but no epidemiological data show higher
      heat-injury rates in children, even during heat waves. We suggest that children
      employ a different thermoregulatory strategy. In extreme temperatures, they may
      indeed be more vulnerable, but under most ambient conditions they are not
      necessarily inferior to adults. Children rely more on dry heat dissipation by
      their larger relative skin surface area than on evaporative heat loss. This also
      enables them to evaporate sweat more efficiently with the added bonus of
      conserving water better than adults.

PMID- 18347700
TI  - Dynamic modulation transfer function: a method to characterize the temporal
      performance of liquid-crystal displays.
AB  - A method to measure the dynamic modulation transfer function (DMTF) of a liquid
      crystal display (LCD) is proposed to characterize its performance when rendering
      motion images. The method includes a measurement system to capture the temporal
      luminance variation of a LCD while using a well-designed input data sequence and
      a simulation model based on smooth pursuit eye tracking and temporal light
      integration at the human retina. It predicts the perceived performance of a
      moving sine wave pattern on a LCD and subsequently calculates the DMTF. With this
      approach, several technologies to reduce motion blur were evaluated and
      discussed.

PMID- 18347701
TI  - Miniaturized fiber inline Fabry-Perot interferometer fabricated with a
      femtosecond laser.
AB  - We report a miniaturized inline Fabry-Perot interferometer directly fabricated on
      a single-mode optical fiber with a femtosecond laser. The device had a loss of 16
      dB and an interference visibility exceeding 14 dB. The device was tested and
      survived in high temperatures up to 1100 degrees C. With an accessible cavity and
      all-glass structure, the new device is attractive for sensing applications in
      high-temperature harsh environments.

PMID- 18347702
TI  - Femto-Newton light force measurement at the thermal noise limit.
AB  - The measurement of very small light forces has wide applications in many fields
      of physics. A common measurement method for small force detection is the
      determination of changes in the dynamic behavior of mechanical oscillators,
      either in amplitude or in frequency. The detection of slowly varying forces
      mostly requires long period oscillators, such as a torsion pendulum. We
      demonstrate the application of a macroscopic, low-noise, torsion balance
      oscillator for the detection of radiation pressure forces at the femto-Newton
      level. The system is "precooled" (removing excess seimic noise) to be only
      thermal noise limited. The demonstrated force sensitivity reaches the thermal
      limit.

PMID- 18347703
TI  - Multiple-image hiding by information prechoosing.
AB  - The information inevitably lost in multiple-image hiding is discarded in advance
      by the operation of prechoosing information before the hiding process; thus both
      fidelity and multiplexing capacity can be improved significantly. Various
      characters of each image provide a great many possibilities for information
      prechoosing. The ideal low-pass filter presented with the matched encoding and
      hiding procedure may be one of the simplest examples of information prechoosing
      for generally used images. Computer simulations demonstrate its good performance,
      and the security is analyzed as well.

PMID- 18347704
TI  - Near-infrared metamaterial films with reconfigurable transmissive/reflective
      properties.
AB  - A near-infrared metamaterial design that is reconfigurable between almost
      completely transmissive and reflective states is presented. The reconfiguration
      is enabled by tuning the anisotropic nematic liquid crystals used as a spacer
      layer between two silver nanoplates in a planar doubly periodic metamaterial. The
      design is optimized for maximum difference in transmittance between the two
      states by using a genetic algorithm. For a linearly polarized illumination at
      normal incidence, full-wave electromagnetic analysis predicts that the optimized
      metamaterial film can change the transmittance between 98.7% and 0.1% at a
      wavelength of 1.1 microm.

PMID- 18347705
TI  - Optofluidic variable aperture.
AB  - A variable aperture has been fabricated and demonstrated using
      polydimethylsiloxane-based optofluidic technology. The device consists of a
      deformable membrane, an air pressure chamber, a cavity filled with light
      absorbing liquid, and a rigid transparent upper plate. The working principle of
      the device is based on the deformable capability of the thin membrane structure
      and its resultant contact with the rigid plate. The contact area can be easily
      controlled by varying the air volume introduced and hence can serve as a light
      transmission aperture. Experimental results show that aperture diameter can be
      continuously changed from zero to 6.35 mm.

PMID- 18347706
TI  - Plasmonic electro-optic modulator design using a resonant metal grating.
AB  - A plasmonic electro-optic modulator design using an evanescently coupled resonant
      metal grating is numerically studied in this Letter. Owing to excitation and
      propagation of long-range surface plasmons between the metal grating nanowires, a
      deep and narrow reflection dip can be obtained. Improved modulation performance
      is achieved through decreased damping from large dielectric gaps between the
      grating nanowires. An optimized electro-optic modulator design with lower
      insertion loss and low operating voltage is presented.

PMID- 18347707
TI  - Photonic generation of a microwave signal by incorporating a delay interferometer
      and a saturable absorber.
AB  - A novel approach to generate microwave signals is presented by employing a dual
      wavelength erbium-doped fiber ring laser. By using a delay interferometer as a
      comb filter cascaded with a tunable bandpass filter and a saturable absorber
      formed by an unpumped polarization-maintaining erbium-doped fiber, a stable
      wavelength-tunable dual-wavelength single longitudinal-mode laser is achieved. A
      microwave signal at 20.07 GHz with a linewidth of <25 kHz is demonstrated by
      beating the two wavelengths at a photodetector.

PMID- 18347708
TI  - Random lasing in freely suspended dye-doped nematic liquid crystals.
AB  - Random lasing in fully disordered systems having organic and inorganic nature has
      been the subject of extensive studies since the beginning of the past decade. The
      interest mainly emerges from the unexpected role played by disorder in the laser
      action. The disorder was considered detrimental for the optical feedback in
      cavity laser, until it was demonstrated that multiple-scattering materials
      including a gain medium act as random laser. Here, a completely new approach is
      reported, where freely suspended complex fluid films doped with fluorescent
      molecules under optical excitation generate narrowband lasing peaks. The
      constellation of localized modes is selected by properly choosing the gain
      profile. The idea to have laser action in absence of mirrors and boundaries
      realizes an unparalleled tunable and moldable laser source.

PMID- 18347709
TI  - Spectral-purity-enhancing layer for multilayer mirrors.
AB  - We demonstrate, both theoretically and experimentally, that special spectral
      purity-enhancing multilayer mirror systems can be designed and fabricated to
      substantially reduce the level of out-of-band radiation expected in an extreme
      ultraviolet lithographic tool. A first proof of principle of applying such
      spectral-purity-enhancement layers showed reduced out-of-band reflectance by a
      factor of five, while the in-band reflectance is only 4.5% (absolute) less than
      for a standard capped multilayer.

PMID- 18347710
TI  - Highly sensitive refractometer with a photonic-crystal-fiber long-period grating.
AB  - We present highly sensitive refractometers based on a long-period grating in a
      large-mode-area photonic crystal fiber (PCF). The maximum sensitivity is 1500
      nm/refractive index unit at a refractive index of 1.33, to our knowledge the
      highest reported for any fiber grating. The minimal detectable index change is 2
      x 10(-5). The high sensitivity is obtained by infiltrating the sample into the
      holes of the PCF to give a strong interaction between the sample and the probing
      field.

PMID- 18347711
TI  - Optimization of multiplexed holographic gratings in PQ-PMMA for spectral-spatial
      imaging filters.
AB  - Holographic gratings formed in thick phenanthrenquinone- (PQ-) doped poly(methyl
      methacrylate) (PMMA) can be made to have narrowband spectral and spatial
      transmittance filtering properties. We present the design and performance of
      angle-multiplexed holographic filters formed in PQ-PMMA at 488 nm and
      reconstructed with a LED operated at approximately 630 nm. The dark delay time
      between exposure and the preillumination exposure of the polymer prior to
      exposure of the holographic area are varied to optimize the diffraction
      efficiency of multiplexed holographic filters. The resultant holographic filters
      can enhance the performance of four-dimensional spatial-spectral imaging systems.
      The optimized filters are used to simultaneously sample spatial and spectral
      information at five different depths separated by 50 microm within biological
      tissue samples.

PMID- 18347712
TI  - Enhancement of band-edge emission induced by defect transition in the composite
      of ZnO nanorods and CdSe/ZnS quantum dots.
AB  - A new and general approach to enhance band-edge emission at the expense of defect
      emission in a semiconductor nanocomposite is proposed. The underlying mechanism
      is based on the resonance effect between defect transition and band-to-band
      excitation and transfer of excited electrons between conduction band edges. With
      our approach, it is possible to convert defect loss into bandgap emission. As an
      example, we demonstrate that the bandgap emission of ZnO nanorods can be enhanced
      by as much as 30 times when they are compounded with CdSe/ZnS nanoparticles.

PMID- 18347713
TI  - Generalized wavefront phase for non-Kolmogorov turbulence.
AB  - We introduce the Levy fractional Brownian field family to model the turbulent
      wavefront phase. This generalized model allows us to overcome the limitations
      found in a previous approach [Perez et al., J. Opt. Soc. Am. A 21, 1962 (2004)].
      More precisely, our new model provides stationary phase increments over the full
      inertial range. Thus it successfully extends classical results to non-Kolmogorov
      turbulence without any approximation.

PMID- 18347714
TI  - Refractive and reflective behavior of polymer prisms used for surface plasmon
      guidance.
AB  - Two-dimensional optics with surface plasmons was realized by the use of
      topographically structured dielectric polymer coatings. Triangles of
      polymethylmetacrylate (PMMA) with lateral dimensions of some tens of micrometers
      on top of a silver layer act as two-dimensional prisms for surface plasmons.
      Refraction and internal reflection of plasmons were investigated by scanning near
      field optical microscopy. The change in propagation direction can be explained by
      Snell's law when taking an effective refractive index for plasmons into account.
      Furthermore, intensity modulations in the PMMA elements and in the transmitted
      plasmon beam were observed.

PMID- 18347715
TI  - Three-core fiber-based shape-sensing application.
AB  - By using specially designed three-core fiber, a microstructured light-pattern
      generator for sensing 3-D shapes has been demonstrated. The square or hexagon
      grid-interferometric fringe pattern formed by the fiber-optic interferometric
      grid generator is projected onto an object's surface. The deformed grid pattern
      containing information of the object's surface topography is captured by a CCD
      camera and is analyzed using 2-D Fourier transforming profilometry. The use of
      the fiber-optic grid-interferogram technique greatly simplifies the holographic
      interferometry system, and the carrier grid interferogram can be conveniently
      generated without the use of excessive auxiliary components or sophisticated
      experimental devices; moreover, the three-core fiber can be used in very narrow
      places, owing to its small size. Finally, the square or hexagon grid
      interferometric fringe pattern provides a data-fusion ability that could further
      improve the accuracy of the 3-D shape-sensing results.

PMID- 18347716
TI  - Optical image encryption based on the multiple-parameter fractional Fourier
      transform.
AB  - A novel image encryption algorithm is proposed based on the multiple-parameter
      fractional Fourier transform, which is a generalized fractional Fourier
      transform, without the use of phase keys. The image is encrypted simply by
      performing a multiple-parameter fractional Fourier transform with four keys.
      Optical implementation is suggested. The method has been compared with existing
      methods and shows superior robustness to blind decryption.

PMID- 18347717
TI  - Continuous sorting of Brownian particles using coupled photophoresis and
      asymmetric potential cycling.
AB  - Feasible sorters need to function rapidly and permit the input and delivery of
      particles continuously. Here, we describe a scheme that incorporates (i)
      restricted spatial input location and (ii) orthogonal sort and movement direction
      features. Sorting is achieved using an asymmetric potential that is cycled on and
      off, whereas movement is accomplished using photophoresis. Simulations with 0.2
      and 0.5 microm diameter spherical particles indicate that sorting can commence
      quickly from a continuous stream. Procedures to optimize the sorting scheme are
      also described.

PMID- 18347718
TI  - Enhanced chaos synchronization in unidirectionally coupled vertical-cavity
      surface-emitting semiconductor lasers with polarization-preserved injection.
AB  - We experimentally study chaos synchronization in unidirectionally coupled
      vertical-cavity surface-emitting semiconductor lasers (VCSELs) with polarization
      preserved and polarization-selected optical injection. The measurements show, in
      agreement with theoretical predictions, that the maximum cross coefficient of
      0.884 obtained with polarization-preserved optical injection is significantly
      higher than the maximum cross coefficient of 0.724 obtained with polarization
      selected optical injection.

PMID- 18347719
TI  - Highly efficient, low-cost femtosecond Cr3+ :LiCAF laser pumped by single-mode
      diodes.
AB  - We describe efficient continuous-wave (cw) and cw mode-locked operations of a
      Cr3+ :LiCAF laser, pumped by inexpensive single spatial mode laser diodes. Up to
      280 mW of cw output power was obtained with 570 mW of absorbed pump power, with a
      corresponding slope efficiency of 54%. Continuous tuning between 765 and 865 nm
      was demonstrated using a fused silica prism. A semiconductor saturable absorber
      mirror was used to initiate and sustain stable, self-starting, mode-locked
      operation. In cw mode locking, the laser produced 72 fs (FWHM) duration pulses,
      and 1.4 nJ pulse energy, at an average output power of 178 mW. Electrical to
      optical conversion efficiencies of 7.8% in mode-locked operation and 12.2% in cw
      operation were demonstrated.

PMID- 18347720
TI  - Fiber-based source of photon pairs at telecom band with high temporal coherence
      and brightness for quantum information processing.
AB  - We experimentally demonstrate a bright pulsed source of correlated photon pairs
      at the 1550 nm telecom band by pumping 300 m dispersion-shifted fiber with a 4 ps
      pulse train. We investigate the coherence property of the source by measuring the
      second-order intensity correlation function g(2) of individual signal (idler)
      photons. A preliminary Hong-Ou-Mandel-type two-photon interference experiment
      with two such sources confirms the high temporal and spatial coherence of the
      source. The source is suitable for multiphoton quantum interference of
      independent sources, which is required in quantum information processing.

PMID- 18347721
TI  - Spiral-path high-sensitivity silicon photonic wire molecular sensor with
      temperature-independent response.
AB  - We demonstrate a new silicon photonic wire waveguide evanescent field (PWEF)
      sensor that exploits the strong evanescent field of the transverse magnetic mode
      of this high-index-contrast, submicrometer-dimension waveguide. High sensitivity
      is achieved by using a 2 mm long double-spiral waveguide structure that fits
      within a compact circular area of 150 microm diameter, facilitating compatibility
      with commercial spotting apparatus and the fabrication of densely spaced sensor
      arrays. By incorporating the PWEF sensor element into a balanced waveguide Mach
      Zehnder interferometer circuit, a minimum detectable mass of approximately 10 fg
      of streptavidin protein is demonstrated with near temperature-independent
      response.

PMID- 18347722
TI  - Precision steering of an optical trap by electro-optic deflection.
AB  - We designed, constructed, and tested a single-beam optical trapping instrument
      employing twin electro-optic deflectors (EODs) to steer the trap in the specimen
      plane. Compared with traditional instruments based on acousto-optic deflectors
      (AODs), EOD-based traps offer a significant improvement in light throughput and a
      reduction in deflection-angle (pointing) errors. These attributes impart improved
      force and position resolution, making EOD-based traps a promising alternative for
      high-precision nanomechanical measurements of biomaterials.

PMID- 18347723
TI  - Interferometric polarization coherent anti-Stokes Raman scattering (IP-CARS)
      microscopy.
AB  - We report a novel interferometry-based polarization coherent anti-Stokes Raman
      scattering (IP-CARS) implementation for effectively suppressing the nonresonant
      background while significantly amplifying the resonant signal for vibrational
      imaging. By modulating the phase difference between the two interference CARS
      signals generated from the same sample and measuring the peak-to-peak intensity
      of the periodically modulated interference CARS signal, the IP-CARS technique
      yields a sixfold improvement in the signal-to-background ratio compared with
      conventional CARS while providing an approximately 20-fold amplification of the
      resonant CARS signal compared with conventional polarization CARS. We demonstrate
      this method by imaging 4.69 microm polystyrene beads and unstained human
      epithelial cells immersed in water.

PMID- 18347724
TI  - Wavelength and intensity switching in directly coupled semiconductor microdisk
      lasers.
AB  - We demonstrate output wavelength and intensity switching in a three-element
      directly coupled microdisk device consisting of one spiral microdisk coupled to
      two semicircle microdisks. The gapless coupling mechanism used allows individual
      elements to achieve lasing while achieving optimal transfer of optical power
      between adjacent microdisks. By controlling the transparency of the center
      element via injection current, the edge elements can be allowed to exchange their
      amplified spontaneous emission. In this manner, on-off-on switching of the output
      intensity, as well as discontinuous shifts in the output wavelength, can be
      achieved as a function of increasing injection current.

PMID- 18347725
TI  - Critical separation for efficient Tm3+ -Tm3+ energy transfer evidenced in
      nanostructured Tm3+: Al2O3 thin films.
AB  - Nanostructured amorphous Al oxide (a-Al2O3) thin films doped with Tm3+ were
      synthesized by alternate pulsed laser deposition. The Tm3+ ions have been
      deposited in layers with in-depth separation ranging from 0.75 to 6 nm. The films
      show two broad emission bands originated from the Tm3+ 3H4-->3F4 and 3F4-->3H6
      transitions. Their intensity increases at a similar rate and the lifetimes are
      not modified as the layer separation decreases down to 1.5 nm, suggesting that
      there is no concentration quenching. At the critical value of 1.5 nm the onset of
      Tm3+ -Tm3+ energy transfer is evidenced by a sharp decrease of the emission
      intensity and lifetime. Below this critical value, the rate at which the
      intensity increases for the 3F4-->3H6 transition is much higher than that for the
      3H4-->3F4 transition, evidencing quenching of the 3H4-->3F4 transition through a
      cross-relaxation mechanism. The control of the Tm3+ ions in the nanometer scale
      allows evidencing the onset of energy transfer processes among ions and offers a
      route to optimize compact photonic gain integrated devices.

PMID- 18347726
TI  - Diamond nanocrystals hosting single nitrogen-vacancy color centers sorted by
      photon-correlation near-field microscopy.
AB  - Diamond nanocrystals containing highly photoluminescent color centers are
      attractive, nonclassical, and near-field light sources. For near-field
      applications, the size of the nanocrystal is crucial, since it defines the
      optical resolution. Nitrogen-vacancy (NV) color centers are efficiently created
      by proton irradiation and annealing of a nanodiamond powder. Using near-field
      microscopy and photon statistics measurements, we show that nanodiamonds with
      sizes down to 25 nm can hold a single NV color center with bright and stable
      photoluminescence.

PMID- 18347727
TI  - Distributed feedback fiber laser pumped by multimode laser diodes.
AB  - A distributed feedback fiber laser made of highly Er-Yb codoped phosphate glass
      fiber has been demonstrated experimentally. Efficient pump absorption allows for
      multimode pumping into the cladding of the active fiber. Output powers up to 160
      mW have been achieved. The 35 mm long fiber laser device emits with >50 dB side
      mode suppression ratio.

PMID- 18347728
TI  - Sidelobe reduction of tightly focused radially higher-order Laguerre-Gaussian
      beams using annular masks.
AB  - We report the reduction of sidelobes in tight focusing patterns of radially
      higher-order Laguerre-Gaussian (LG) beams with nonhelical phase structures.
      Numerical calculations based on the vectorial Debye theory reveal that a class of
      annular masks reduces sidelobes in the tight focusing patterns only for radially
      even-order LG beams. The present scheme produces small focal spots beyond the
      diffraction limit suitable for application to scanning microscopy, laser fine
      processing, etc.

PMID- 18347730
TI  - Broadband light generation at approximately 1300 nm through spectrally recoiled
      solitons and dispersive waves.
AB  - We experimentally study the generation of broadband light at approximately 1300
      nm from an 810 nm Ti:sapphire femtosecond pump laser. We use two photonic crystal
      fibers with a second infrared zero-dispersion wavelength (lambda Z2) and compare
      the efficiency of two schemes: in one fiber lambda Z2=1400 nm and the light at
      1300 nm is composed of spectrally recoiled solitons; in the other fiber lambda
      Z2=1200 nm and the light at 1300 nm is composed of dispersive waves.

PMID- 18347731
TI  - Scattering differentiates Alzheimer disease in vitro.
AB  - The molecular bases of Alzheimer disease and related neurodegenerative disorders
      are becoming better understood, but the means for definitive diagnosis and
      monitoring in vivo remain lacking. Near-infrared optical spectroscopy offers a
      potential solution. We acquired transmission and reflectance spectra of thin
      brain tissue slabs, from which we calculated wavelength-dependent absorption and
      reduced scattering coefficients from 470-1000 nm. The reduced scattering
      coefficients in the near infrared clearly differentiated Alzheimer from control
      specimens. Diffuse reflectance spectra of gross brain tissue in vitro confirmed
      this observation. These results suggest a means for diagnosing and monitoring
      Alzheimer disease in vivo, using near-infrared optical spectroscopy.

PMID- 18347732
TI  - Combined Mueller and Jones matrix method for the evaluation of the complex
      modulation in a liquid-crystal-on-silicon display.
AB  - We apply the polar decomposition of the Mueller matrix describing a liquid
      crystal-on-silicon display to identify the diattenuator, depolarizer, and
      retarder contributions as a function of the gray level. The retarder contribution
      is expressed in terms of the equivalent Jones matrix to apply previous techniques
      to evaluate the phase modulation. This allows searching for optimized
      polarization configurations for phase- or amplitude-only modulation responses. We
      present results for lambda=633 nm showing a phase-only modulation up to 2 pi rad
      and flat intensity modulation.

PMID- 18347733
TI  - Simultaneous time- and wavelength-resolved fluorescence spectroscopy for near
      real-time tissue diagnosis.
AB  - A novel fiber-optic-based method for simultaneous time- and wavelength-resolved
      fluorescence spectroscopy for the rapid diagnosis of diseased tissue is
      demonstrated. By combining multiple bandpass and dichroic filters (405/40,
      460/50, and 550/50) with different lengths of optical fiber (1, 10, and 19 m)
      acting as an optical delay this system enables the near real-time acquisition and
      characterization of time-resolved fluorescence spectra using a single detector
      and excitation input. The recording of multiple fluorescence response pulses at
      selected wavelengths can be completed in hundreds of nanoseconds, which provides
      the capability of a real-time characterization of biological systems.

PMID- 18347734
TI  - Turbulence-induced square-root broadening of the Raman fiber laser output
      spectrum.
AB  - The output characteristics of the conventional one-stage Raman fiber laser (RFL)
      are described in an optical wave turbulence formalism. Simple analytical
      expressions describing RFL output power and its spectral shape are presented, and
      square-root law for the output spectrum broadening law has been discovered. The
      indications of the turbulent-like spectral broadening in other types of cw fiber
      lasers and propagation phenomena in fibers are also discussed.

PMID- 18347735
TI  - A novel high-capacity ion trap-quadrupole tandem mass spectrometer.
AB  - We describe a prototype tandem mass spectrometer that is designed to increase the
      efficiency of linked-scan analyses by >100-fold over conventional linked-scan
      instruments. The key element of the mass spectrometer is a novel high ion
      capacity ion trap, combined in tandem configuration with a quadrupole collision
      cell and a quadrupole mass analyzer (i.e. a TrapqQ configuration). This ion trap
      can store >10(6) ions without significant degradation of its performance. The
      current mass resolution of the trap is 100-450 full width at half maximum for
      ions in the range 800-4000 m/z, yielding a 10-20 m/z selection window for ions
      ejected at any given time into the collision cell. The sensitivity of the mass
      spectrometer for detecting peptides is in the low femtomole range. We can
      envisage relatively straightforward modifications to the instrument that should
      improve both its resolution and sensitivity. We tested the tandem mass
      spectrometer for collecting precursor ion spectra of all the ions stored in the
      trap and demonstrated that we can selectively detect a phosphopeptide in a
      mixture of non-phosphorylated peptides. Based on this prototype instrument, we
      plan to construct a fully functional model of the mass spectrometer for detecting
      modification sites on proteins and profiling their abundances with high speed and
      sensitivity.

PMID- 18347736
TI  - Child mental representations of attachment when mothers are traumatized: The
      relationship of family-drawings to story-stem completion.
AB  - This study examines the relationship between child play-narratives and family
      drawings by children of violence-exposed mothers with posttraumatic stress
      disorder (PTSD). The Family Attachment Drawing Task (FAD-T) and MacArthur Story
      Stem Battery (MSSB) were administered. Of the 23 children (ages 4-7 years), 16
      (70%) created drawings that were coded as being representative of insecure
      attachment. Attachment insecurity and disorganization of child-caregiver
      attachment on the FAD-T were significantly associated with trauma-related
      dimensions of the MSSB, but not to other factors. This study suggests that the
      FAD-T provides access to child mental representations, which may affect
      intergenerational transmission of violent trauma.

PMID- 18347737
TI  - Small-bodied humans from Palau, Micronesia.
AB  - Newly discovered fossil assemblages of small bodied Homo sapiens from Palau,
      Micronesia possess characters thought to be taxonomically primitive for the genus
      Homo. BACKGROUND: Recent surface collection and test excavation in limestone
      caves in the rock islands of Palau, Micronesia, has produced a sizeable sample of
      human skeletal remains dating roughly between 940-2890 cal ybp. PRINCIPLE
      FINDINGS: Preliminary analysis indicates that this material is important for two
      reasons. First, individuals from the older time horizons are small in body size
      even relative to "pygmoid" populations from Southeast Asia and Indonesia, and
      thus may represent a marked case of human insular dwarfism. Second, while
      possessing a number of derived features that align them with Homo sapiens, the
      human remains from Palau also exhibit several skeletal traits that are considered
      to be primitive for the genus Homo. SIGNIFICANCE: These features may be
      previously unrecognized developmental correlates of small body size and, if so,
      they may have important implications for interpreting the taxonomic affinities of
      fossil specimens of Homo.

PMID- 18347738
TI  - Infection of semen-producing organs by SIV during the acute and chronic stages of
      the disease.
AB  - BACKGROUND: Although indirect evidence suggests the male genital tract as a
      possible source of persistent HIV shedding in semen during antiretroviral
      therapy, this phenomenon is poorly understood due to the difficulty of sampling
      semen-producing organs in HIV+ asymptomatic individuals. METHODOLOGY/PRINCIPAL
      FINDINGS: Using a range of molecular and cell biological techniques, this study
      investigates SIV infection within reproductive organs of macaques during the
      acute and chronic stages of the disease. We demonstrate for the first time the
      presence of SIV in the testes, epididymides, prostate and seminal vesicles as
      early as 14 days post-inoculation. This infection persists throughout the chronic
      stage and positively correlates with blood viremia. The prostate and seminal
      vesicles appear to be the most efficiently infected reproductive organs, followed
      by the epididymides and testes. Within the male genital tract, mostly T
      lymphocytes and a small number of germ cells harbour SIV antigens and RNA. In
      contrast to the other organs studied, the testis does not display an immune
      response to the infection. Testosteronemia is transiently increased during the
      early phase of the infection but spermatogenesis remains unaffected.
      CONCLUSIONS/SIGNIFICANCE: The present study reveals that SIV infection of the
      macaque male genital tract is an early event and that semen-producing organs
      display differential infection levels and immune responses. These results help
      elucidate the origin of HIV in semen and constitute an essential base to
      improving the design of antiretroviral therapies to eradicate virus from semen.

PMID- 18347739
TI  - Automatic physiological waveform processing for FMRI noise correction and
      analysis.
AB  - Functional MRI resting state and connectivity studies of brain focus on neural
      fluctuations at low frequencies which share power with physiological fluctuations
      originating from lung and heart. Due to the lack of automated software to process
      physiological signals collected at high magnetic fields, a gap exists in the
      processing pathway between the acquisition of physiological data and its use in
      fMRI software for both physiological noise correction and functional analyses of
      brain activation and connectivity. To fill this gap, we developed an open source,
      physiological signal processing program, called PhysioNoise, in the python
      language. We tested its automated processing algorithms and dynamic signal
      visualization on resting monkey cardiac and respiratory waveforms. PhysioNoise
      consistently identifies physiological fluctuations for fMRI noise correction and
      also generates covariates for subsequent analyses of brain activation and
      connectivity.

PMID- 18347740
TI  - Electrical brain responses in language-impaired children reveal grammar-specific
      deficits.
AB  - BACKGROUND: Scientific and public fascination with human language have included
      intensive scrutiny of language disorders as a new window onto the biological
      foundations of language and its evolutionary origins. Specific language
      impairment (SLI), which affects over 7% of children, is one such disorder. SLI
      has received robust scientific attention, in part because of its recent linkage
      to a specific gene and loci on chromosomes and in part because of the prevailing
      question regarding the scope of its language impairment: Does the disorder impact
      the general ability to segment and process language or a specific ability to
      compute grammar? Here we provide novel electrophysiological data showing a domain
      specific deficit within the grammar of language that has been hitherto
      undetectable through behavioural data alone. METHODS AND FINDINGS: We presented
      participants with Grammatical(G)-SLI, age-matched controls, and younger child and
      adult controls, with questions containing syntactic violations and sentences
      containing semantic violations. Electrophysiological brain responses revealed a
      selective impairment to only neural circuitry that is specific to grammatical
      processing in G-SLI. Furthermore, the participants with G-SLI appeared to be
      partially compensating for their syntactic deficit by using neural circuitry
      associated with semantic processing and all non-grammar-specific and low-level
      auditory neural responses were normal. CONCLUSIONS: The findings indicate that
      grammatical neural circuitry underlying language is a developmentally unique
      system in the functional architecture of the brain, and this complex higher
      cognitive system can be selectively impaired. The findings advance fundamental
      understanding about how cognitive systems develop and all human language is
      represented and processed in the brain.

PMID- 18347741
TI  - [Tuberculosis and immigration in Spain].

PMID- 18347742
TI  - [Incentives in primary care from cost containment to public health].

PMID- 18347743
TI  - [Tuberculosis in the Autonomous region of Madrid, Spain. Incidence among foreign
      and Spanish individuals during the 1996-2004 period].
AB  - BACKGROUND: Immigration from countries having a high prevalence of tuberculosis
      to other more highly-developed countries has a bearing on the overall evolution
      of tuberculosis in the latter. This study is aimed at describing the influence of
      the cases of tuberculosis among foreign individuals on the incidence of this
      disease in the Autonomous Community of Madrid during the 1996-2004 period.
      METHODS: The data was taken from the Regional Tuberculosis Case Registry and from
      the 1996 census and the continuous censuses from 1998 to 2004. The tuberculosis
      incidence was estimated by country of origin from 1996 to 2004, by gender and by
      age groups. A calculation was made of the c2 for the linear trend, reasons for
      incidence and proportion of cases among foreign individuals. RESULTS: The
      incidence of tuberculosis went from 34.3 cases per 105 inhabitants in 1996 to
      16.9 cases per 105 inhabitants in 2004. For those born in Spain, it changed from
      33.2 cases per 105 inhabitants in 1996 to 12.7 cases per 105 inhabitants in 2004;
      and for foreign individuals, from 50.5 cases per 105 inhabitants in 1996 to 42.9
      cases per 105 inhabitants in 2004. The reason for the incidence between foreign
      and Spanish individuals was greater than 1 for all years, the maximum figure
      having been in 2003, when 4.2 cases were detected among foreigners for every case
      among Spanish individuals (95% CI 3.7-4.7). The percentage of foreign cases went
      from 5.2% in 1996 to 35.1% in 2004. CONCLUSIONS: The incidence of tuberculosis
      among foreigners was greater than among Spanish individuals and did not
      significantly decrease in the 1996-2004 period, which is contributing to
      tuberculosis having stabilized. This situation and the characteristics of this
      population must be taken into account in the efforts for controlling this
      disease.

PMID- 18347744
TI  - [G1 mumps virus outbreak in the province of Almeria in 2005].
AB  - BACKGROUND: Despite high levels of triple MMR vaccinations being recorded on
      Spain, epidemic mumps outbreaks are still being reported. This study is aimed at
      describing an outbreak reported in the province of Almeria in 2005 and of
      evaluating the degree to which the vaccinated population was affected. METHODS:
      Descriptive study of reported cases. VARIABLES STUDIED: Basic Health District,
      municipality, age, sex, type of population (Spanish-born and foreign), date of
      symptom onset, symptoms, complications, vaccination status, vaccine strain and
      diagnostic testing. INFORMATION SOURCES: disease reporting files, epidemiological
      surveys, microbiological data, vaccination card, District vaccine software and
      Andalusian Institute of Statistics demographic data. Rates per 100,000
      inhabitants were calculated by age groups and population type. The Student's t
      test was used for comparing means. RESULTS: A total of 145 cases from 17
      municipalities were reported. A total 63.4% were males. The group showing the
      highest incidence was that of 10-14 years of age, with a rate of 405 per 100,000.
      The highest rate was among the Spanish-born population (128.7). A total of 52.4%
      of the cases were found to have been administered some dose of vaccine, 69.7% of
      them with two doses and 71.1% some Jeryl Lynn strain. Mumps virus was confirmed
      in 43 cases, the G1 genotype having been identified in 6 cases. CONCLUSIONS: An
      outbreak of G1 genotype mumps virus is confirmed, the Spanish-born population of
      different age groups having been affected to a greater extent. Over half of the
      cases were vaccinated individuals.

PMID- 18347745
TI  - [Evaluation of the effectiveness of preventive activities (Strategic Action
      Plans) on the incidence of non-fatal traumatic occupational injuries leading to
      disabilities in Spain (1994-2004)].
AB  - BACKGROUND: [corrected] The strategic action plans have been the main preventive
      activities carried out by the Autonomous Community Governments in relation to
      occupational injuries in Spain since 1999. This study is aimed at evaluating the
      effectiveness of these plans. METHODS: A total of 4,714,080 cases of non-fatal
      traumatic occupational injuries leading to disability having occured within the
      1994-2004 period due to mechanical causes and over-exertion at non-publicly owned
      service and manufacturing companies were included. Based on the annual incidence
      rates, the percentage of annual change and the 95% confidence interval (95% CI)
      were estimated for the periods prior to and following the start-up of the
      Strategic Action Plans by means of negative binomial regression. RESULTS: The
      pattern found followed an upward trend during the periods prior to the start-up
      of the Strategic Actions Plans, followed by a downward trend as of the start-up
      of these plans. For example, in Aragon, where the Strategic Action Plan was
      started up in 999, a +5.3% rise was found within the 1994-1999 period, as
      compared to a -4.9% decrease during the 2000-2004 period. On the Balearic
      Islands, which started up their Strategic Action Plan in 2002, the corresponding
      trend was +5.4% for 1994-2001, as compared to -14% for 2002-2004. However,
      similar trends were found in Madrid (-3.9% for 2000-2004) or in Galicia (-4.8%
      for 2000-2004), where there is no record of any specific Strategic Action Plan
      having been gotten under way during the period under study. CONCLUSIONS: These
      results do not make it possible to attribute the widespread drop in the non-fatal
      traumatic occupational injury incidence as of 2000 in Spain to the Strategic
      Action Plans. Possibly other actions of a general nature which may have had a
      bearing on all of the Autonomous Communities in the same manner (including those
      which have not developed their own Strategic Action Plans) might explain this
      drop in the incidence of the occupational injuries selected in this analysis.

PMID- 18347746
TI  - [Functional capacity for daily living activities among senior citizens attending
      Community Centers in the city of Zaragoza, Spain, 2005].
AB  - BACKGROUND: To study the dependence related to aging is of particular interest in
      Aragon, where the population is one of the most aged in Spain. The objective of
      this study is that of quantifying the degree of functional dependence for daily
      living activities (DLA) and identifying the personal traits related thereto among
      individuals age 65 and above who are living at home and attend Community Centers
      in the city of Zaragoza. METHODS: Cross-sectional study with 380 individuals
      selected by two-stage sampling. The OARS-MFAQ questionnaire was used by way of
      personal interviews, analyzing questions which assess the functional capacity to
      carry out the DLA's and their scoring (dependent variable), sociodemographic
      variables, self-assessed health condition and actual and hypothetical informal
      help (independent variables). The chi-square was used for evaluating classified
      residual data (p<0.05) and multiple correspondence analyses. RESULTS: A total of
      9.6% of the subjects showed "major/total dependence", this percentage increasing
      to 15.5% and 18.7% for those individuals above age 75 and 80, respectively. The
      "minor/moderate dependence" is related to being a female (p<0.01), health
      condition self-assessed as poor-passable (p<0.0001), being a widow(er) (p<0.01),
      having no elementary school education (p<0.01). CONCLUSIONS: Those individuals
      who are more elderly, females, widow/widowers, having a lesser degree of
      education and worse self-assessed health condition are more dependent.
      Practically one out of every ten non-institutionalized individuals 65 years of
      age or over shows a severe deterioration of their functional capacity.
      Extrapolating, nearly 11,000 individuals in the city of Zaragoza would require
      daily help for the DLA's or should stay institutionalized.

PMID- 18347747
TI  - [Design and validation of a questionnaire of the hospital outpatient clinics in
      Madrid, Spain, 2006].
AB  - BACKGROUND: In order to improve the quality of health care it is necessary to
      know the point of view of the patients through satisfaction surveys. Satisfaction
      surveys need some psychometric properties to guarantee its reliability and
      validity. The aim of this paper is to design and to validate a questionnaire to
      determine the satisfaction of patients of the hospital outpatient clinics.
      METHODS: Validation of a satisfaction questionnaire, designed by an expert group
      and composed for 12 questions. The questionnaire was given to a sample of 677
      patients attended in the hospital Gregorio Maranon outpatient clinics. The
      psychometric properties of the questionnaire were established: construct
      validity, concurrent criterion validity, predictive capacity and internal
      consistency. RESULTS: Two dimensions were identified in the construct validity
      analyses, explaining 63% of the variance: "clinical quality" and "administrative
      quality". The concurrent validity analysis showed a Spearman's rank correlation
      coefficient of 0.85 related to the standard criterion "global satisfaction with
      the attention provided in outpatient clinics" and an OR of 1.19 related to the
      criterion "do you know the name of the physician who attended you?" The
      predictive capacity of the questionnaire was measured by discriminated analysis,
      obtaining 84% of correct classified, and the internal consistency test gave a
      Cronbach's alpha of 0.90. CONCLUSIONS: Our questionnaire has enough psychometric
      properties to be considered an useful and feasible tool to measure the
      satisfaction of patients of the hospital outpatient clinics.

PMID- 18347748
TI  - [Prevalence of certain osteoporosis-determining habits among post menopausal
      women in the Basque Country, Spain, in 2003].
AB  - BACKGROUND: [corrected] On planning health promotion strategies for a disease or
      condition, one must know the current situation of the factors which have a
      bearing thereon. This study is aimed at analyzing, in the Basque Country, those
      living habits which interact to control the maximum bone density peak in
      postmenopausal women. METHODS: This study was conducted in February-May 2003 on a
      sample of 555 women over 45 years of age selected at random in the Basque
      Country. A total of 82.8% thereof answered a living habit survey and a three-day
      recall diet survey. A descriptive core trend study was made for quantitative
      variable and frequencies for qualitative variables. A comparison was drawn
      between the prevalence among groups selected by way of the chi-square test and
      Student's t-test. RESULTS: A total of 27.4% of the women studied were over 65
      years of age (average age 58.51). Forty percent (40%) of the women were actively
      involved in physical exercise. A total of 4.1% of the women had sun exposure
      occasionally or exceptionally. The average calcium intake was 788.17 mg/day
      (SD=218.35). A total 0.3% had risk-level alcohol consumption and 14.7% moderate
      consumption. In relation to smoking, 12.6% of the women in the sample smoked less
      than a pack a day, and 3.5% more than one pack a day. CONCLUSIONS: The women
      studied showed as risk factors for having osteoporosis: a low level of active
      exercise, low calcium intake and in those women younger that 65 years of age and
      high degree of smoking.

PMID- 18347749
TI  - [Access to cervical cytology in Medellin, Colombia during 2006].
AB  - BACKGROUND: The burden of illness of cervical cancer has not decreased enough in
      developing countries. For that reason is important to improve coverage, access
      and effectiveness of cervical cancer screening programs. The objective of this
      paper is to analyze women's access to the cervical cytology programme of the
      Secretary of Health of Medellin (Colombia). METHODS: An analysis was made of
      1,519 records of women from a cross-sectional study conducted in an urban area of
      Medellin (Colombia). Descriptive analysis was conducted and a Logit model was
      estimated for analysing recent cervical cytology (cytology performed less than 36
      months prior to the survey). RESULTS: 68.7% of women had a recent cytology, 17.2%
      did not have recent cytology and 14.2% of women attended for the first time to
      the service. The probability of having a recent cytology increased with age,
      women with family history of cervical cancer, women with personal history of
      sexually transmitted infections, women with some education and women who are (or
      were) married or in a stable union. CONCLUSIONS: The demand for cytology appears
      to be concentrated; a limited number of women assist frequently while others
      don't practice it or stop assisting.

PMID- 18347750
TI  - The determinants and outcomes of long-stay psychiatric admissions: a case-control
      study.
AB  - BACKGROUND: Acute psychiatric admissions lasting over 6 months (long-stays)
      continue to occur in England. Previous studies have suggested an association
      between long-stay and both schizophrenia and challenging behaviour, as well as
      rehousing or placement difficulties, but no UK study to date has compared such
      cases with control admissions. METHODS: We performed a case-control study. All
      long-stay patients present on acute general psychiatric wards serving the London
      Boroughs of Croydon, Lambeth, Lewisham and Southwark on November 1st 2004 were
      compared with a group of 'next admitted' controls. We followed up long-stay cases
      1 year later to determine whether they were still in hospital, and, if not, where
      they were living. RESULTS: In unadjusted comparisons long stay was associated
      with schizophrenia, non-white ethnicity, admission not due to suicidality,
      violence, severe illness and need for rehousing. A logistic regression was used
      to adjust for associations among exposures and only violence, severity of illness
      and need for rehousing remained associated with long-stay. After 1 year, two
      thirds of cases were living out of hospital. CONCLUSIONS: Case-control studies
      may usefully contribute to the study of the complex social phenomenon of long
      stay. Further research should address how the combination of individual and
      socially-determined effects that we found operate together over the course of
      admission to generate long-stays.

PMID- 18347751
TI  - Diversifying and purifying selection in the peptide binding region of DRB in
      mammals.
AB  - The class II genes of the major histocompatibility complex encode proteins which
      play a crucial role in antigen presentation. They are among the most polymorphic
      proteins known, and this polymorphism is thought to be the result of natural
      selection. To understand the selective pressure acting on the protein and to
      examine possible differences in the evolutionary dynamics among species, we apply
      maximum likelihood models of codon substitution to analyze the DRB genes of six
      mammalian species: human, chimpanzee, macaque, tamarin, dog, and cow. The models
      account for variable selective pressures across codons in the gene and have the
      power to detect amino acid residues under either positive or negative selection.
      Our analysis detected positive selection in the DRB genes in each of the six
      mammals examined. Comparison with structural data reveals that almost all amino
      acid residues inferred to be under positive selection in humans are in the
      peptide binding region (PBR) and are in contact with the antigen side chains,
      although residues outside of but close to the PBR are also detected. Strong
      purifying selection is also detected in the PBR, at sites which contact the
      antigen and at sites which may be involved in dimerization or T cell binding. The
      analysis demonstrates the utility of the random-sites analysis even when
      structural information is available. The different mammalian species are found to
      share many positively or negatively selected sites, suggesting that their
      functional roles have remained very similar in the different species, despite the
      different habitats and pathogens of the species.

PMID- 18347752
TI  - Novelty and spatio-temporal heterogeneity in the bacterial diversity of
      hypersaline Lake Tebenquiche (Salar de Atacama).
AB  - Lake Tebenquiche is one of the largest saline water bodies in the Salar de
      Atacama at 2,500 m above sea level in northeastern Chile. Bacteria inhabiting
      there have to deal with extreme changes in salinity, temperature and UV dose
      (i.e., high environmental dissimilarity in the physical landscape). We analyzed
      the bacterioplankton structure of this lake by 16S rRNA gene analyses along a
      spatio-temporal survey. The bacterial assemblage within the lake was quite
      heterogeneous both in space and time. Salinity changed both in space and time
      ranging between 1 and 30% (w/v), and total abundances of planktonic prokaryotes
      in the different sampling points within the lake ranged between two and nine
      times 10(6) cells mL(-1). Community composition changed accordingly to the
      particular salinity of each point as depicted by genetic fingerprinting analyses
      (denaturing gradient gel electrophoresis), showing a high level of variation in
      species composition from place to place (beta-diversity). Three selected sites
      were analyzed in more detail by clone libraries. We observed a predominance of
      Bacteroidetes (about one third of the clones) and Gammaproteobacteria (another
      third) with respect to all the other bacterial groups. The diversity of
      Bacteroidetes sequences was large and showed a remarkable degree of novelty.
      Bacteroidetes formed at least four clusters with no cultured relatives in
      databases and rather distantly related to any known 16S rRNA sequence. Within
      this phylum, a rich and diverse presence of Salinibacter relatives was found in
      the saltiest part of the lake. Lake Tebenquiche included several novel
      microorganisms of environmental importance and appeared as a large unexplored
      reservoir of unknown bacteria.

PMID- 18347753
TI  - Species segregation in one-dimensional granular-system simulations.
AB  - We present one-dimensional molecular dynamics simulations of a two-species,
      initially uniform, freely evolving granular system. Colliding particles swap
      their relative position with a 50% probability allowing for the initial spatial
      ordering of the particles to evolve in time and frictional forces to operate.
      Unlike one-dimensional systems of identical particles, two-species one
      dimensional systems of quasi-elastic particles are ergodic and the particles'
      velocity distributions tend to evolve towards Maxwell-Boltzmann distributions.
      Under such conditions, standard fluid equations with merely an additional sink
      term in the energy equation, reflecting the non-elasticity of the interparticle
      collisions, provide an excellent means to investigate the system's evolution.
      According to the predictions of fluid theory we find that the clustering
      instability is dominated by a non-propagating mode at a wavelength of the order
      10 pi L/N epsilon , where N is the total number of particles, L the spatial
      extent of the system and epsilon the inelasticity coefficient. The typical fluid
      velocities at the time of inelastic collapse are seen to be supersonic, unless N
      epsilon<or= 10 pi . Species segregation, driven by the frictional force occurs as
      a result of the strong temperature gradients within clusters which pushes the
      light particles towards the clusters' edges and the heavy particles towards the
      center. Segregation within clusters is complete at the time of inelastic
      collapse.

PMID- 18347754
TI  - Expression, purification and characterization of TAT-high mobility group box-1A
      peptide as a carrier of nucleic acids.
AB  - High mobility group box 1 (HMGB1) is an abundant nuclear protein that binds to
      double-stranded DNA. HMGB1 is composed of high mobility (HMG) box A, box B, and C
      terminal acidic regions. In this study, a recombinant TAT linked HMGB1 box A
      (rTAT-HMGB1A) peptide was expressed, purified, and characterized as a carrier of
      nucleic acids. The HMGB1A cDNA was amplified by PCR, and cloned into the pET21a
      expression vector with the TAT domain located at the N-terminus. The rTAT-HMGB1A
      peptide was overexpressed and purified using Nickel affinity chromatography. A
      recombinant HMGB1A (rHMGB1A) peptide without the TAT domain was also
      overexpressed and purified as a control. In gel retardation assays, both the
      rHMGB1A and rTAT-HMGB1A peptides formed complexes with DNA equally well. However,
      transfection assays showed that the rTAT-HMGB1A peptide had a higher gene
      transfer efficiency than rHMGB1A. Finally, rTAT-HMGB1A had no cytotoxicity to HEK
      293 cells suggesting that rTAT-HMGB1A may be useful as a non-toxic gene delivery
      carrier.

PMID- 18347755
TI  - Species richness and the analytic geometry of latitudinal and altitudinal
      gradients.
AB  - Extensive empirical work has shown that species richness decreases roughly
      exponentially or quadratically with latitude. What appears to be a latitudinal
      gradient in fact may simply be a negative correlation of latitude with area at
      that latitude, due to convergence of lines of meridian at the poles. There is
      simply less area at high latitudes, which means fewer niches and fewer
      opportunities for speciation, hence diminished biodiversity at high latitudes.
      Similarly, analytic geometry of a cone shows that species number should decrease
      linearly with altitude on a conical mountain. Here, I provide an explicit
      mathematical model of the area hypothesis of species richness along latitude and
      altitude gradients. I re-analyze a previously published latitudinal gradient
      dataset and show that species number is a linear function of the predicted area
      and that species number is more fully explained by predicted area than by a
      quadratic function of latitude. However, analytic geometry is not needed if
      precise measures of area are known.

PMID- 18347756
TI  - Genomic regulation of intestinal amino acid transporters by aldosterone.
AB  - Overexpression of renal LAT2, a Na+ -independent L-amino acid transporter, in
      spontaneous hypertensive rats (SHR) is organ specific and precedes the onset of
      hypertension (Pinho et al., Hypertension, 42:613-618, 2003). However, the
      expression of LAT2 correlates negatively with plasma aldosterone levels after
      high sodium intake (Pinho et al., Am J Physiol Ren Physiol 292:F1452-F1463,
      2007). The present study evaluated the expression of Na+ -independent LAT1, LAT2,
      and 4F2hc and Na+ -dependent ASCT2 amino acid transporters in the intestine of
      normotensive Wistar rats chronically treated with aldosterone. In conditions of
      high salt intake, to keep endogenous aldosterone to a minimum, rats were
      implanted with aldosterone or spironolactone tablets. In aldosterone-treated and
      aldosterone + spironolactone-treated rats, aldosterone plasma levels were
      increased by fourfold. At the protein level, aldosterone treatment significantly
      increased LAT1 (62%), LAT2 (49%), 4F2hc (48%), and ASCT2 (65%) expression. The
      effect of aldosterone upon LAT1, LAT2, 4F2hc, and ASCT2 protein abundance was
      completely reversed by spironolactone. Aldosterone significantly increased
      intestinal LAT2 and 4F2hc mRNA levels (27% and 35% increase, respectively), with
      no changes in LAT1 and ASCT2 transcript levels. In conclusion, increases in
      intestinal Na+ -independent LAT1 and LAT2 and Na+ -dependent ASCT2 transcript and
      protein abundance during chronic treatment with aldosterone occur through a
      spironolactone-sensitive genomic mechanism.

PMID- 18347757
TI  - Irish contributions to the origins of antibiotics.
AB  - BACKGROUND: Pasteur commented that if we could intervene in the antagonism
      observed between some bacteria, it would offer 'perhaps the greatest hopes for
      therapeutics.' Some Irish scientists were crucially involved in the eventual
      realization of these hopes. RESEARCH: The earliest of these was John Tyndall,
      whose 1881 book, 'Floating matter in the air in relation to putrefaction and
      infection,' brought about general acceptance of Pasteur's germ theory. Sir
      Almroth Wright, a TCD graduate, who discovered the first vaccine against typhoid
      fever, recruited Alexander Fleming to the London hospital where he discovered
      penicillin. SEQUENCE OF EVENTS: This happened when Fleming was replicating an
      experiment originally carried out by Bigger, Boland and O'Meara in TCD. One of
      Fleming's cultures was accidentally contaminated by a mould containing penicillin
      which came from the collection of Charles La Touche, an Irish mycologist who was
      researching whether cobwebs caused asthma in the same hospital, and who later
      taught in UCD.

PMID- 18347758
TI  - Vanadium uptake by biomass of Coprinus comatus and their effect on hyperglycemic
      mice.
AB  - The Vanadium uptake by Coprinus comatus and their co-effect on hyperglycemic mice
      were studied. By fermentation and AAS analysis, the optimal concentration of
      vanadium in medium was 0.4%, and the content of vanadium accumulated in the
      mycelia was 3,528.0 microg/g. At the concentration of 0.4%, the vanadium
      associated toxicity was reduced, and its anti-diabetic effects were maintained.

PMID- 18347759
TI  - The co-effect of vanadium and fermented mushroom of Coprinus comatus on glycaemic
      metabolism.
AB  - The effect of fermented mushroom of Coprinus comatus rich in vanadium (CCRV) on
      glycaemic metabolism was studied in this paper. Alloxan-induced hyperglycemic
      mice were used in this study. The insulin secretion and glycogen synthesis of the
      mice were analyzed. At the same time, the gluconeogenesis of the normal mice was
      also determined. The alloxan-damaged pancreatic beta-cells of the mice were also
      studied in this paper. After the mice were administered (i.g.) with CCRV, the
      level of insulin secretion and glycogen synthesis of alloxan-induced
      hyperglycemic mice elevated (p<0.05, p<0.01) and the gluconeogenesis of the
      normal mice was inhibited (p<0.01). Also, the alloxan-damaged pancreatic beta
      cells of the mice were partly recovered gradually after the mice were
      administered (i.g.) with CCRV 15 days later. These may account for the causes of
      CCRV-induced significant decreases of the blood glucose in hyperglycemic mice.

PMID- 18347760
TI  - Takotsubo cardiomyopathy associated with seizures.
AB  - BACKGROUND: Takotsubo syndrome is a reversible neuromyocardial failure that has
      been thought to be related to an acute catecholamine toxicity of the myocardium
      brought upon by a stressful event. The neurocritical care unit population is
      particularly vulnerable for this condition given the acute presentation of
      neurological emergencies, which most often can be catastrophic. We present a case
      series of this syndrome and a review of the literature. METHOD: Our recent
      experience with three cases that were prospectively identified with the diagnosis
      of Takotsubo syndrome is reported with clinical presentation, evaluation, and
      management approach. Review of the literature is presented in the discussion.
      RESULTS: We present three episodes of Takotsubo neuromyocardial syndrome in two
      patients that were admitted to our neurointensive care unit that presented with
      seizures and had typical clinical presentation, echocardiographic and cardiac
      catheterization findings. All the episodes were treated with vasoactive
      medications, ventilatory support, afterload and preload reduction, and treatment
      of the underlying condition. There was complete reversal of their symptoms and
      findings in each episode. CONCLUSIONS: Patients with critical neurological
      illnesses such as large ischemic or hemorrhagic stroke, status epilepticus,
      recurrent seizure activities as in our study may be at a higher risk for
      Takotsubo neuromyocardial syndrome.

PMID- 18347762
TI  - [Procedural analgesia : concepts and practice].
AB  - The effect of severe pain and its hazardous stress-related cardiocirculatory
      consequences have been well documented for the perisurgical setting.
      Independently of surgical intervention however, even short and simple measures
      (e.g. thorax drain removal, repositioning a limb fracture) and longer diagnostic
      procedures such as MRI are potentially very painful or stressful to the patient.
      Though longer diagnostic procedures are frequently supported by systemic
      medication, short interventions regularly lack this aspect. Specific challenges
      result from the need to counteract sometimes great changes in pain intensity.
      Moreover procedural analgesia represents a multidisciplinary measure not
      restricted to anaesthesiology, as most of these measures are performed without
      anaesthesia. To avoid endangering the patient, the choice of drugs and patient
      monitoring have to meet certain professional and technical standards. Competence
      in respiratory management is of paramount importance. This paper outlines these
      requirements and serves as an orientation outside the anaesthesiological
      speciality.

PMID- 18347763
TI  - [Effectiveness of radiofrequency ablation of lung tumours ].
AB  - BACKGROUND: There has been great success in the treatment of primary and
      secondary tumours of the liver using radiofrequency ablation (RFA) therapy,
      resulting in this method being used for other solid tumours such as in the lung.
      However, concerning lung cancer only few data are available about the
      histomorphological effects of this method. The aim of this study was to analyse
      the effects of RFA therapy in tumours of the lung. PATIENTS AND METHODS: Eleven
      patients with non-small-cell lung cancer and one with a lung metastasis (primary
      tumour identified as urothelial carcinoma) underwent RFA therapy followed by
      resection of the affected lobe. One patient with a metastasis of the liver was
      included for comparison of treatment effects. Histomorphological analysis of the
      collected material was used to measure the amount of necrosis. RESULTS: None of
      the treated tumours of the lung showed complete necrosis after applying RFA
      therapy. In contrast, this method with the control metastasis of the liver
      resulted in complete thermal destruction. CONCLUSION: Our results indicate that
      RFA therapy is not adequate for successful induction of necrosis in tumours of
      the lung. Therefore the use of this method has to be considered extremely
      carefully as a palliative treatment option in tumours of the lung.

PMID- 18347764
TI  - [Brachytherapy in combination with function-preserving surgery. An
      interdisciplinary challenge].
AB  - A multimodal, interdisciplinary approach known as intensity-modified
      brachytherapy is a promising alternative for patients with advanced head and neck
      cancer infiltrating the orbita and skull base. An 87-year-old man presented with
      a recurrence of squamous cell carcinoma of the medial corner of the left eye that
      had been locally resected and irradiated by external beam radiotherapy multiple
      times. The cancer was resected with preservation of the eye with close margins,
      implantation of afterloading catheters, and reconstruction of the defect with a
      median forehead flap. The patient was irradiated with a total radiation dose of
      30 Gy IMBT. After 1 year, there was no evidence of locoregional recurrence. The
      background of this therapeutic process and analysis of the current literature
      regarding this interdisciplinary treatment of head and neck cancer infiltrating
      the orbita and skull base are discussed based on this case report.

PMID- 18347765
TI  - Primary ICD-therapy in patients with advanced heart failure: selection strategies
      and future trials.
AB  - BACKGROUND: For allocation of primary ICD-therapy, a possible lower limit of
      inclusion criteria--defining overly advanced heart failure--is less well
      investigated. Also, a multi-variable approach to stratification beyond ejection
      fraction (LVEF) appears warranted. We examined whether adding a selection limit
      of peak VO(2) <or= 14 ml/kg/min to LVEF <or= 20% improves stratification.
      Furthermore, we sought to provide current survival data and a size-estimate for
      prospective trials based on real-life data for this high risk cohort. METHODS: In
      our prospective clinical registry 1,926 patients with systolic CHF were recruited
      consecutively since 1994. Of these patients, 292 met the selection criteria
      described above. The mean age was 57.6 +/- 9.5 years, 83% were male, 37% had
      ischemic cardiomyopathy and 28% received primary ICD-therapy. All cause mortality
      was considered as end point. RESULTS: Median follow-up was 45 (18-86) months. ICD
      was not a significant predictor of outcome either for the entire population, or
      grouped according to aetiology of CHF. Still, 3-year mortality was 15% (ICD
      patients) Vs. 28% (non-ICD-patients); P = 0.05; under combination medical
      therapy. Inversely, in ICD-patients medical combination therapy conveyed a
      significant survival benefit (P < 0.001). Consequently, the number-needed-to
      treat was eight under combination therapy and the size estimate amounts to 300
      patients for a prospective trial in this cohort. CONCLUSION: A cut-off of LVEF
      <or= 20% and pVO(2) <or= 14 ml/kg/min could identify patients that do not draw a
      significant survival benefit from adjunct primary ICD-therapy. Our results
      indicate the need for a specific randomized trial in this cohort. The according
      mortality data and a size estimate are provided.

PMID- 18347766
TI  - Balloon valvuloplasty of aortic valve stenosis in childhood: early and medium
      term results.
AB  - BACKGROUND: Isolated aortic valve stenosis in childhood is treated by balloon
      valvuloplasty. The role of independent risk factors for the outcome remains
      unclear. MATERIAL AND METHODS: We analysed the early and medium term outcome of
      balloon valvuloplasty in isolated aortic valve stenosis in 44 pediatric patients
      with isolated, severe aortic valve stenosis at an age younger than 18 years, who
      received a primary balloon valvuloplasty during the last 5 years in our
      institution. We evaluated the type of aortic valve morphology, age, clinical
      status, and myocardial function at the time of the intervention as independent
      risk factor. RESULTS: A significant early relief of the pressure gradient across
      the aortic valve (P < 0.001) after balloon valvuloplasty was found. This was
      independent of the aortic valve morphology. Two neonates with a highly stenotic
      tricuspid aortic valve and severely compromised haemodynamics died within the
      first 30 days after the intervention. During medium term follow up (mean 22.5
      months) we observed a functional deterioration for the stenosis as well as for
      the insufficiency of the aortic valve. "Symptoms before intervention" is an
      independent risk factors (P < 0.001) for valvuloplasty failure. Patients at an
      "age at intervention <or= 28 days" (P = 0.02) and patients with "reduced
      myocardial systolic function" (P = 0.01) had a shorter time to reintervention.
      CONCLUSIONS: The type of aortic valve morphology only has a weak predictive value
      for the outcome of balloon valvuloplasty during medium term follow up. Critical
      ill neonates with an impaired myocardial function are at a higher risk for
      valvuloplasty failure.

PMID- 18347767
TI  - Vascular endothelial functions, carotid intima-media thickness, and soluble CD40
      ligand levels in dipper and nondipper essential hypertensive patients.
AB  - OBJECTIVE: The lack of nocturnal decline in blood pressure (BP) is associated
      with an increase in cardiovascular events. Soluble CD40 ligand (sCD40L) is
      involved in the pathogenesis of risk factor-related vascular damage. The purpose
      of this study was to examine the relationship between vascular endothelial
      functions, carotid intima-media thickness (cIMT), plasma sCD40L levels and
      circadian BP profile in patients with essential hypertension. MATERIAL AND
      METHODS: The study population consisted of 81 essential hypertensive out
      patients. BP dipping was defined as a night-to-day systolic and diastolic
      decrease >or=10%. Forty-seven dipper and 34 nondipper patients were compared.
      High sensitivity C-reactive protein (hs-CRP), sCD40L and urinary albumin were
      measured. Brachial artery flow-mediated dilatation (FMD) and cIMT was compared
      between the groups. RESULTS: sCD40L level (3.28 +/- 2.08 and 2.30 +/- 1.99 ng/ml,
      respectively, P = 0.036) and urinary albumin concentration (36.7 +/- 20.1 and 23
      +/- 29.7 mg/l, respectively, P < 0.0001) were higher in nondippers than in
      dippers. Serum hs-CRP levels were not significantly different. FMD was found
      higher in dippers than nondippers (11.8 +/- 3.9% and 6.6 +/- 2.2%, respectively,
      P < 0.0001). The average cIMT was significantly higher in nondippers than dippers
      (0.928 +/- 0.060 Vs. 0.734 +/- 0.134 mm; P < 0.0001). CONCLUSIONS: Nondipper
      patern has an additional negative effect on endothelial functions in hypertensive
      patients. Nondippers have enhanced sCD40L levels, which may contribute to their
      increased susceptibility to develop vascular damage.

PMID- 18347768
TI  - Pulmonary vein stents in infants and children: is there lasting benefit?

PMID- 18347769
TI  - Digital preparation of a probable neoceratopsian preserved within an egg, with
      comments on microstructural anatomy of ornithischian eggshells.
AB  - We describe the first known embryo of a neoceratopsian dinosaur, perhaps the most
      ubiquitous Laurasian group of Cretaceous dinosaurs, which is preserved completely
      enclosed within an egg. This specimen was collected from Late Cretaceous beds of
      southern Mongolia, which commonly preserve fossils of the neoceratopsian,
      Yamaceratops dorngobiensis. The small egg was scanned using high-resolution X-ray
      computed tomography and digitally prepared from the matrix. The preserved and
      imaged elements support a diagnosis of the embryo to Neoceratopsia and allow
      preliminary observations of ontogenetic transformations within this group. The
      addition of an embryo also adds another important data point to the already
      impressive postnatal ontogenetic series that are available for this clade.

PMID- 18347770
TI  - [The role of radiologists in emergency medicine and shock room management--new
      challenges!].

PMID- 18347771
TI  - [Value of breast MRI as supplement to mammography and sonography for high risk
      breast cancer patients].
AB  - PURPOSE: The aim of this study is to give an overview on early detection of
      breast cancer in patients with an increased risk of breast cancer. Sensitivities
      and diagnostic accuracies of breast MRI, mammography and ultrasound were
      compared. MATERIAL AND METHODS: A systematic literature search of the past 3
      years was performed. Studies which compared breast imaging modalities and used
      image-guided biopsy results as standard of reference were included. Patients
      included had to have had an increased lifetime risk for breast cancer (>15%).
      RESULTS: Regarding sensitivity and diagnostic accuracy, breast MRI performed best
      in comparison to the other modalities within this collective of patients.
      Sensitivities ranged from 71-100%, 0-78%, and 13-65%, for MRI, mammography, and
      ultrasound, respectively CONCLUSION: Breast MRI is a well established tool for
      screening in patients at high risk for developing breast cancer and is a valuable
      supplement to mammography and ultrasound within this selected cohort of patients.

PMID- 18347772
TI  - The adult plant rust resistance loci Lr34/Yr18 and Lr46/Yr29 are important
      determinants of partial resistance to powdery mildew in bread wheat line Saar.
AB  - Powdery mildew, caused by Blumeria graminis f. sp. tritici is a major disease of
      wheat (Triticum aestivum L.) that can be controlled by resistance breeding. The
      CIMMYT bread wheat line Saar is known for its good level of partial and race non
      specific resistance, and the aim of this study was to map QTLs for resistance to
      powdery mildew in a population of 113 recombinant inbred lines from a cross
      between Saar and the susceptible line Avocet. The population was tested over 2
      years in field trials at two locations in southeastern Norway and once in
      Beijing, China. SSR markers were screened for association with powdery mildew
      resistance in a bulked segregant analysis, and linkage maps were created based on
      selected SSR markers and supplemented with DArT genotyping. The most important
      QTLs for powdery mildew resistance derived from Saar were located on chromosomes
      7DS and 1BL and corresponded to the adult plant rust resistance loci Lr34/Yr18
      and Lr46/Yr29. A major QTL was also located on 4BL with resistance contributed by
      Avocet. Additional QTLs were detected at 3AS and 5AL in the Norwegian testing
      environments and at 5BS in Beijing. The population was also tested for leaf rust
      (caused by Puccinia triticina) and stripe rust (caused by P. striiformis f. sp.
      tritici) resistance and leaf tip necrosis in Mexico. QTLs for these traits were
      detected on 7DS and 1BL at the same positions as the QTLs for powdery mildew
      resistance, and confirmed the presence of Lr34/Yr18 and Lr46/Yr29 in Saar. The
      powdery mildew resistance gene at the Lr34/Yr18 locus has recently been named
      Pm38. The powdery mildew resistance gene at the Lr46/Yr29 locus is designated as
      Pm39.

PMID- 18347773
TI  - Susceptibility to Fusarium head blight is associated with the Rht-D1b semi
      dwarfing allele in wheat.
AB  - Fusarium head blight (FHB) is an important disease of wheat worldwide. The
      cultivar Spark is more resistant than most other UK winter wheat varieties but
      the genetic basis for this is not known. A mapping population from a cross
      between Spark and the FHB susceptible variety Rialto was used to identify
      quantitative trait loci (QTL) associated with resistance. QTL analysis across
      environments revealed nine QTL for FHB resistance and four QTL for plant height
      (PH). One FHB QTL was coincident with the Rht-1D locus and accounted for up to
      51% of the phenotypic variance. The enhanced FHB susceptibility associated with
      Rht-D1b is not an effect of PH per se as other QTL for height segregating in this
      population have no influence on susceptibility. Experiments with near-isogenic
      lines supported the association between susceptibility and the Rht-D1b allele
      conferring the semi-dwarf habit. Our results demonstrate that lines carrying the
      Rht-1Db semi-dwarfing allele are compromised in resistance to initial infection
      (type I resistance) while being unaffected in resistance to spread within the
      spike (type II resistance).

PMID- 18347774
TI  - A grapevine (Vitis vinifera L.) genetic map integrating the position of 139
      expressed genes.
AB  - Grapevine molecular maps based on microsatellites, AFLP and RAPD markers are now
      available. SSRs are essential to allow cross-talks between maps, thus upgrading
      any growing grapevine maps. In this work, single nucleotide polymorphisms (SNPs)
      were developed from coding sequences and from unique BAC-end sequences, and
      nested in a SSR framework map of grapevine. Genes participating to flavonoids
      metabolism and defence, and signal transduction pathways related genes were also
      considered. Primer pairs for 351 loci were developed from ESTs present on public
      databases and screened for polymorphism in the "Merzling" (a complex genotype
      Freiburg 993-60 derived from multiple crosses also involving wild Vitis species)
      x Vitis vinifera (cv. Teroldego) cross population. In total 138 SNPs, 108 SSR
      markers and a phenotypic trait (berry colour) were mapped in 19 major linkage
      groups of the consensus map. In specific cases, ESTs with putatively related
      functions mapped near QTLs previously identified for resistance and berry
      ripening. Genes related to anthocyanin metabolism mapped in different linkage
      groups. A myb gene, which has been correlated with anthocyanin biosynthesis,
      cosegregated with berry colour on linkage group 2. The possibility of associating
      candidate genes to known position of QTL is discussed for this plant.

PMID- 18347775
TI  - The flowering locus Hr colocalizes with a major QTL affecting winter frost
      tolerance in Pisum sativum L.
AB  - An understanding of the genetic determinism of frost tolerance is a prerequisite
      for the development of frost tolerant cultivars for cold northern areas. In
      legumes, it is not known to which extent vernalization requirement or photoperiod
      responsiveness are necessary for the development of frost tolerance. In pea
      (Pisum sativum L.) however, the flowering locus Hr is suspected to influence
      winter frost tolerance by delaying floral initiation until after the main winter
      freezing periods have passed. The objective of this study was to dissect the
      genetic determinism of frost tolerance in pea by QTL analysis and to assess the
      genetic linkage between winter frost tolerance and the Hr locus. A population of
      164 recombinant inbred lines (RILs), derived from the cross Champagne x Terese
      was evaluated both in the greenhouse and in field conditions to characterize the
      photoperiod response from which the allele at the Hr locus was inferred. In
      addition, the population was also assessed for winter frost tolerance in 11 field
      conditions. Six QTL were detected, among which three were consistent among the
      different experimental conditions, confirming an oligogenic determinism of frost
      tolerance in pea. The Hr locus was found to be the peak marker for the highest
      explanatory QTL of this study. This result supports the hypothesis of the
      prominent part played by the photoperiod responsiveness in the determinism of
      frost tolerance for this species. The consistency of three QTL makes these
      positions interesting targets for marker-assisted selection.

PMID- 18347776
TI  - Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting
      effects on blood pressure, endothelial function, glycaemic control and hormonal
      profiles.
AB  - AIMS/HYPOTHESIS: Aldosterone antagonism improves endothelial function (and
      reduces deaths) in chronic heart failure. It is not known whether similar effects
      occur in other high-risk groups such as patients with diabetes and hypertension.
      We therefore assessed the full effects of aldosterone blockade in poorly
      controlled hypertensive patients with type 2 diabetes, focussing on blood
      pressure, endothelial function, glycaemic control and key hormones. METHODS: We
      performed a randomised, placebo-controlled, double-blind, crossover study on 50
      patients with type 2 diabetes and treated but poorly controlled hypertension,
      comparing spironolactone versus placebo. Patients had their endothelial function
      assessed by standard forearm venous occlusion plethysmography. RESULTS: There was
      no significant improvement in endothelium-dependent vasodilatation in response to
      acetylcholine, despite highly significant reductions in systolic and diastolic
      blood pressure. However, spironolactone significantly worsened glycaemic control,
      plasma angiotensin II and cortisol. CONCLUSIONS/INTERPRETATION: Spironolactone is
      highly effective in lowering blood pressure in patients with type 2 diabetes and
      poorly controlled hypertension on standard treatment, but does not improve
      vascular endothelial function in this group. We speculate that any tendency for
      the spironolactone-induced lowering of blood pressure to improve endothelial
      function is offset by its tendency to worsen glycaemic control and increase the
      levels of angiotensin II and even possibly cortisol.

PMID- 18347778
TI  - Influence of deposit stage and failed ESWT on the surgical results of
      arthroscopic treatment of calcifying tendonitis of the shoulder.
AB  - The purpose of the present study is the evaluation of a possible influence of the
      preoperative deposit stage, the postoperative deposit elimination and failed
      preoperative extracorporeal shockwave therapy on the surgical outcome of
      arthroscopic treatment of tendinosis calcarea. From 1997 to 2004, 65 patients
      underwent arthroscopic resection of calcific deposits of the shoulder after
      failed conservative treatment. Patients with rotator cuff tears, major cartilage
      damage, or previous surgery were excluded. Out of 50 patients 45 (17 men, 28
      women) that could be contacted with a mean age of 49 +/- 8 years could be
      followed-up with a mean of 36 months (14-89) after surgery. A total of 24
      patients (53.3%) underwent preoperative extracorporeal shock-wave therapy (ESWT).
      For the clinical evaluation the Constant and Murley Score, the Simple Shoulder
      Test, the Western Ontario Rotator Cuff Index (WORC) and visual analog scales for
      pain, function and satisfaction were used. For the radiological evaluation, the
      classifications according to Gaertner and Bosworth were used. Statistical
      analysis was done with the Wilcoxon test, the Mann-Whitney test and ANOVA. The
      Constant and Murley Score improved significantly from preoperative 63.5 +/- 11.4
      to postoperative 93.9 +/- 9.9 points (P < .0001) at follow-up, the Simple
      Shoulder Test from 1.7 +/- 2 to 9.9 +/- 2.8 points (P < .0001), the WORC score
      from 1,591.2 +/- 337.4 to 345.4 +/- 392 points (P < .0001). The visual analog
      scales for pain, function and patient satisfaction also significantly improved (P
      < .0001). Preoperative radiological evaluation according to the Gaertner
      classification revealed 37 type I deposits, 6 type II and 2 type III deposits;
      postoperative no calcific deposits were seen in 37 patients, 6 type I and 2 type
      III deposits. According to the Bosworth classification 13 type I, 19 type II and
      13 type III deposits were seen preoperatively. Postoperative X-rays showed 6 type
      I and 1 type II and III deposits. There was no significant correlation of the
      clinical results with the pre- or postoperative findings. The 24 patients who
      underwent ESWT before surgery did not show significantly better results than
      patients without ESWT. In conclusion, arthroscopic removal of calcific deposits
      of the shoulder shows good clinical results for pain reduction, shoulder function
      and patient satisfaction. The type of calcific deposit and the preoperative
      treatment of the shoulder with ESWT did not have any significant impact on the
      postoperative results.

PMID- 18347777
TI  - What is the mechanism of microalbuminuria in diabetes: a role for the glomerular
      endothelium?
AB  - Microalbuminuria is an important risk factor for cardiovascular disease and
      progressive renal impairment. This holds true in the general population and
      particularly in those with diabetes, in whom it is common and marks out those
      likely to develop macrovascular disease and progressive renal impairment.
      Understanding the pathophysiological mechanisms through which microalbuminuria
      occurs holds the key to designing therapies to arrest its development and prevent
      these later manifestations. Microalbuminuria arises from the increased passage of
      albumin through the glomerular filtration barrier. This requires ultrastructural
      changes rather than alterations in glomerular pressure or filtration rate alone.
      Compromise of selective glomerular permeability can be confirmed in early
      diabetic nephropathy but does not correlate well with reported glomerular
      structural changes. The loss of systemic endothelial glycocalyx--a protein-rich
      surface layer on the endothelium--in diabetes suggests that damage to this layer
      represents this missing link. The epidemiology of microalbuminuria reveals a
      close association with systemic endothelial dysfunction and with vascular
      disease, also implicating glomerular endothelial dysfunction in microalbuminuria.
      Our understanding of the metabolic and hormonal sequelae of hyperglycaemia is
      increasing, and we consider these in the context of damage to the glomerular
      filtration barrier. Reactive oxygen species, inflammatory cytokines and growth
      factors are key players in this respect. Taken together with the above
      observations and the presence of generalised endothelial dysfunction, these
      considerations lead to the conclusion that glomerular endothelial dysfunction,
      and in particular damage to its glycocalyx, represents the most likely initiating
      step in diabetic microalbuminuria.

PMID- 18347779
TI  - Phylogenetic diversity of nitrogen-fixing bacteria in mangrove sediments assessed
      by PCR-denaturing gradient gel electrophoresis.
AB  - Culture-independent PCR-denaturing gradient gel electrophoresis (DGGE) was
      employed to assess the composition of diazotroph species from the sediments of
      three mangrove ecosystem sites in Sanya, Hainan Island, China. A strategy of
      removing humic acids prior to DNA extraction was conducted, then total community
      DNA was extracted using the soil DNA kit successfully for nifH PCR amplification,
      which simplified the current procedure and resulted in good DGGE profiles. The
      results revealed a novel nitrogen-fixing bacterial profile and fundamental
      diazotrophic biodiversity in mangrove sediments, as reflected by the numerous
      bands present DGGE patterns. Canonical correspondence analysis (CCA) revealed
      that the sediments organic carbon concentration and available soil potassium
      accounted for a significant amount of the variability in the nitrogen-fixing
      bacterial community composition. The predominant DGGE bands were sequenced,
      yielding 31 different nifH sequences, which were used in phylogenetic
      reconstructions. Most sequences were from Proteobacteria, e.g. alpha, gamma,
      beta, delta-subdivisions, and characterized by sequences of members of genera
      Azotobacter, Desulfuromonas, Sphingomonas, Geobacter, Pseudomonas, Bradyrhizobium
      and Derxia. These results significantly expand our knowledge of the nitrogen
      fixing bacterial diversity of the mangrove environment.

PMID- 18347780
TI  - Expression of amphetamine sensitization is associated with recruitment of a
      reactive neuronal population in the nucleus accumbens core.
AB  - RATIONALE: Repeated exposure to psychostimulant drugs causes a long-lasting
      increase in the psychomotor and reinforcing effects of these drugs and an array
      of neuroadaptations. One such alteration is a hypersensitivity of striatal
      activity such that a low dose of amphetamine in sensitized animals produces
      dorsal striatal activation patterns similar to acute treatment with a high dose
      of amphetamine. OBJECTIVES: To extend previous findings of striatal
      hypersensitivity with behavioral observations and with cellular activity in the
      nucleus accumbens and prefrontal cortex in sensitized animals. MATERIALS AND
      METHODS: Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and
      sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for
      stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos
      positive nuclei were quantified in the nucleus accumbens and prefrontal cortex
      after expression of sensitization with 1 mg/kg i.p. amphetamine. RESULTS: Intense
      stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not
      in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to
      amphetamine in the accumbens core was augmented in amphetamine-pretreated animals
      with a shift in the distribution of optical density, while no effect of
      sensitization was seen in the nucleus accumbens shell or prefrontal cortex.
      CONCLUSIONS: A lack of stereotypy in the sensitized group indicates a
      dissociation of behavioral responses to amphetamine and striatal immediate-early
      gene activation patterns. The increase in c-fos positive nuclei and shift in the
      distribution of optical density observed in the nucleus accumbens core suggests
      recruitment of a new population of neurons during expression of sensitization.

PMID- 18347781
TI  - Trends and opportunities in food pathogen detection.

PMID- 18347782
TI  - A microarray chip for label-free detection of narcotics.
AB  - A protein array chip for label-free optical detection of low molecular weight
      compounds has been developed. As a proof of principle, the chip is proven capable
      of rapidly (approximately 1 min) determining hits from aqueous cocktails composed
      of four common narcotics, cocaine, ecstasy, heroin, and amphetamine, using
      imaging surface plasmon resonance (SPR) as the detection principle. The chip is
      produced by injecting a mixture of antibodies and letting them self-sort and bind
      to narcotic analog coupled proteins already present in a predefined pattern on
      the supporting substrate. An indirect detection method, where antibodies are
      displaced from the surface upon recognition of their corresponding narcotics, is
      used to obtain the optical contrast and thus a detectable SPR and/or
      ellipsometric signal. Two types of readouts are possible from the present setup:
      intensity SPR images and SPR/ellipsometric sensorgrams. Positive hits were
      routinely obtained for analyte concentrations of 50 pg/microL and the limit of
      detection, without any parameter optimizations, seems to fall in the range 0.5
      pg/microL (1.4 nM) for heroin, 2.5 pg/microL (8.2 nM) for cocaine, and 5
      pg/microL for the other two narcotics (26 nM for ecstasy and 37 nM for
      amphetamine). With improved readout possibilities (sampling frequency), signal
      evaluation algorithms, and antibody-antigen design strategies, we believe this
      limit can be further improved. The chip is shown to work for many measurement
      cycles with excellent reproducibility. Moreover, with a more advanced fluidic
      system, excess injected antibodies could be collected and reused for many cycles,
      which could make the running costs of the system very low. The chip is in no way
      limited to detection of narcotics. Other low molecular weight compounds could
      easily be detected on the same chip. For example, trinitrotoluene detection has
      already been demonstrated using our chip. Possible areas of application for the
      system are therefore envisaged in airport and underground transport security,
      customs, drug interdiction, forensics, and as warning alerts on military
      equipment and personnel.

PMID- 18347783
TI  - Pedunculopontine nucleus microelectrode recordings in movement disorder patients.
AB  - The pedunculopontine nucleus (PPN) lies within the brainstem reticular formation
      and is involved in the motor control of gait and posture. Interest has focused
      recently on the PPN as a target for implantation of chronic deep brain
      stimulation (DBS) electrodes for Parkinson's disease (PD) and progressive
      supranuclear palsy (PSP) therapy. The aim of this study was to examine the
      neurophysiology of the human PPN region and to identify neurophysiological
      landmarks that may aid the proper placement of DBS electrodes in the nucleus for
      the treatment of PD and PSP. Neuronal firing and local field potentials were
      recorded simultaneously from two independently driven microelectrodes during
      stereotactic neurosurgery for implantation of a unilateral DBS electrode in the
      PPN in five PD patients and two PSP patients. Within the PPN region, the majority
      (57%) of the neurons fired randomly while about 21% of the neurons exhibited
      'bursty' firing. In addition, 21% of the neurons had a long action potential
      duration and significantly lower firing rate suggesting they were cholinergic
      neurons. A change in firing rate produced by passive and/or active contralateral
      limb movement was observed in 38% of the neurons that were tested in the PPN
      region. Interestingly, oscillatory local field potential activity in the beta
      frequency range ( approximately 25 Hz) was also observed in the PPN region. These
      electrophysiological characteristics of the PPN region provide further support
      for the proposed role of this region in motor control. It remains to be seen to
      what extent the physiological characteristics of the neurons and the stimulation
      evoked effects will permit reliable identification of PPN and determination of
      the optimal target for DBS therapy.

PMID- 18347784
TI  - Audio-vocal system regulation in children with autism spectrum disorders.
AB  - Do children with autism spectrum disorders (ASD) respond similarly to
      perturbations in auditory feedback as typically developing (TD) children?
      Presentation of pitch-shifted voice auditory feedback to vocalizing participants
      reveals a close coupling between the processing of auditory feedback and vocal
      motor control. This paradigm was used to test the hypothesis that abnormalities
      in the audio-vocal system would negatively impact ASD compensatory responses to
      perturbed auditory feedback. Voice fundamental frequency (F(0)) was measured
      while children produced an /a/ sound into a microphone. The voice signal was fed
      back to the subjects in real time through headphones. During production, the
      feedback was pitch shifted (-100 cents, 200 ms) at random intervals for 80
      trials. Averaged voice F(0) responses to pitch-shifted stimuli were calculated
      and correlated with both mental and language abilities as tested via standardized
      tests. A subset of children with ASD produced larger responses to perturbed
      auditory feedback than TD children, while the other children with ASD produced
      significantly lower response magnitudes. Furthermore, robust relationships
      between language ability, response magnitude and time of peak magnitude were
      identified. Because auditory feedback helps to stabilize voice F(0) (a major
      acoustic cue of prosody) and individuals with ASD have problems with prosody,
      this study identified potential mechanisms of dysfunction in the audio-vocal
      system for voice pitch regulation in some children with ASD. Objectively
      quantifying this deficit may inform both the assessment of a subgroup of ASD
      children with prosody deficits, as well as remediation strategies that
      incorporate pitch training.

PMID- 18347785
TI  - Striatal neurons encoded temporal information in duration discrimination task.
AB  - To clarify the roles of the basal ganglia in time perception, single-unit
      activity was recorded from both sides of the striatum of a monkey performing a
      duration discrimination task. In the task, two visual cues were presented
      successively in different durations (0.2 approximately 1.6 s). Each cue
      presentation was followed by a 1-s delay period. The subject was instructed to
      choose a longer presented cue after the second delay period. There were two types
      of trials for sequence of cue duration, the long-short (LS) trials in which the
      first cue (C1) was longer than the second cue (C2) and the short-long (SL) trials
      in which the C1 was shorter than the C2. Striatal neurons phasically responded
      during the first delay (D1) and second delay (D2) periods. Responses during the
      D1 period changed depending on C1 duration. Activity of populations of D1
      response neurons correlated with C1 duration positively or negatively. Responses
      during the D2 period differed between the LS and SL trials. Activity of
      population of D2-response neurons also changed depending on C2 duration. But the
      dependence on C2 duration was affected by the trial type, that is, whether the C2
      was longer or shorter compared to the C1. These findings suggest that striatal
      neurons could encode cue durations with monotonically changing responses in the
      D1 period and discrimination results between the two cue durations in the D2
      period.

PMID- 18347786
TI  - ERP correlates of anticipatory attention: spatial and non-spatial specificity and
      relation to subsequent selective attention.
AB  - Brain-based models of visual attention hypothesize that attention-related
      benefits afforded to imperative stimuli occur via enhancement of neural activity
      associated with relevant spatial and non-spatial features. When relevant
      information is available in advance of a stimulus, anticipatory deployment
      processes are likely to facilitate allocation of attention to stimulus properties
      prior to its arrival. The current study recorded EEG from humans during a
      centrally-cued covert attention task. Cues indicated relevance of left or right
      visual field locations for an upcoming motion or orientation discrimination.
      During a 1 s delay between cue and S2, multiple attention-related events occurred
      at frontal, parietal and occipital electrode sites. Differences in anticipatory
      activity associated with the non-spatial task properties were found late in the
      delay, while spatially-specific modulation of activity occurred during both early
      and late periods and continued during S2 processing. The magnitude of
      anticipatory activity preceding the S2 at frontal scalp sites (and not occipital)
      was predictive of the magnitude of subsequent selective attention effects on the
      S2 event-related potentials observed at occipital electrodes. Results support the
      existence of multiple anticipatory attention-related processes, some with
      differing specificity for spatial and non-spatial task properties, and the
      hypothesis that levels of activity in anterior areas are important for effective
      control of subsequent S2 selective attention.

PMID- 18347787
TI  - Effect of aging on the coordination between equilibrium and movement: what
      changes?
AB  - This investigation studies the effect of aging on the coordination between
      equilibrium and trunk movement. Eight young adults and seven adults at the end of
      middle age bent their trunk forward and stabilized their position. The center of
      mass shift was studied as an indicator of equilibrium control as was the
      electromyographic pattern of the main muscles involved in the movement. The
      kinematic strategy responsible for both the movement and equilibrium control was
      quantified by performing a principal components analysis on the hip, knee, ankle
      angle changes occurring during the movement. We observed that the effect of aging
      can be detected early. It is not expressed as a deterioration of equilibrium
      control but rather as "over control". The kinematic strategy is modified, the
      central command adapted. These results could express the onset of a lesser
      ability to simplify the coordination between equilibrium and movement as young
      adults leading to its deterioration in the elderly.

PMID- 18347788
TI  - Unusual stress fracture in an adolescent baseball pitcher affecting the trochlear
      groove of the olecranon.
AB  - Stress fractures of the proximal ulna are known to occur in throwing athletes.
      Most cases extend to involve the olecranon, and cases limited to the trochlear
      groove are rare. In this report we present a 17-year-old elite baseball pitcher
      with a stress fracture of the trochlear groove of the proximal ulna. Diagnosis
      was made by demonstration of characteristic signal changes on MRI of the elbow.
      The fracture occurred at the cortical notch, also known as the pseudodefect of
      the trochlear groove. This case suggests that the cortical notch serves as an
      area of weakness predisposing pitchers to development of a stress fracture.

PMID- 18347789
TI  - Modulation of the conductance of a 2,2'-bipyridine-functionalized peptidic ion
      channel by Ni2+.
AB  - An alpha-helical amphipathic peptide with the sequence H2N-(LSSLLSL)3-CONH2 was
      obtained by solid phase synthesis and a 2,2'-bipyridine was coupled to its N
      terminus, which allows complexation of Ni2+. Complexation of the 2,2'-bipyridine
      residues was proven by UV/Vis spectroscopy. The peptide helices were inserted
      into lipid bilayers (nano black lipid membranes, nano-BLMs) that suspend the
      pores of porous alumina substrates with a pore diameter of 60 nm by applying a
      potential difference. From single channel recordings, we were able to distinguish
      four distinct conductance states, which we attribute to an increasing number of
      peptide helices participating in the conducting helix bundle. Addition of Ni2+ in
      micromolar concentrations altered the conductance behaviour of the formed ion
      channels in nano-BLMs considerably. The first two conductance states appear much
      more prominent demonstrating that the complexation of bipyridine by Ni2+ results
      in a considerable confinement of the observed multiple conductance states.
      However, the conductance levels were independent of the presence of Ni2+.
      Moreover, from a detailed analysis of the open lifetimes of the channels, we
      conclude that the complexation of Ni2+ diminishes the frequency of channel events
      with larger open times.

PMID- 18347790
TI  - Effect of polar and non-polar carotenoids on Xanthophylomyces dendrorhous
      membranes by EPR.
AB  - The red yeast Xanthophyllomyces dendrorhous is one of the microbiological
      production systems for natural carotenoids. High-performance liquid
      chromatography (HPLC) and electron paramagnetic resonance spectroscopy (EPR)
      experiments were performed on X. dendrorhous membranes in order to study the
      effect of incorporation rates of different type of carotenoids. In the case of
      fluid-phase membranes, it was found that polar carotenoids, such as astaxanthin
      and cis-astaxanthin, increased the EPR order parameter and decreased the motional
      freedom and phase-transition temperature. In contrast the non-polar carotenoids
      beta-cryptoxanthin and beta-carotene decreased the EPR order parameter and
      increased motional freedom and phase-transition temperature. A noteworthy
      coherence was observed between the polarities of the strains and the phase
      transition temperatures.

PMID- 18347791
TI  - Construction of a stress-induced system in Escherichia coli for efficient
      polyhydroxyalkanoates production.
AB  - In the application of engineered Escherichia coli in industrial
      polyhydroxybutyrate production process, one of the major concerns is the
      induction of the metabolic pathway. In this study, we developed a stress-induced
      system by which the PHB biosynthesis pathways can be induced under stress
      conditions. Fermentation results showed that recombinant E. coli DH5alpha
      (pQKZ103) harboring this system was able to accumulate polyhydroxybutyrate up to
      85.8% of cell dry weight in minimal glucose medium without adding any inducer.
      Growth experiment with GFP as a reporter indicated that the induction of this
      system happened at the late exponential phase and was sensitive to stressed
      environment. This system can also be applied in many other biotechnological
      processes.

PMID- 18347792
TI  - Quantifying the surface characteristics and flocculability of Ralstonia eutropha.
AB  - The microbial surface and flocculability were qualitatively characterized through
      the combination of the surface thermodynamic and the extended DLVO approaches,
      with Ralstonia eutropha, a polyhydroxybutyrate-producing bacterium, as an
      example. The negativity of the zeta potential of R. eutropha decreased from the
      initial -19.5 to -11 mV in its cultivation with the consumption of glucose. The
      total interfacial free energy (DeltaGadh) was changed from -80 to 28.5 mJ m(-2)
      in its entire growth process. This suggests that the bacterial surface changed
      from hydrophobic into hydrophilic, resulting in an alteration of its surface
      characteristics and flocculability in its different growth phases. As a result,
      the stability ratio of suspensions increased with the increasing cultivation
      time, indicating that the cell particles became more repulsive with each other
      and led to a more stable suspension of R. eutropha in its cultivation. The
      obtained information in this work might be useful for better understanding the
      surface characteristics and the flocculability and even manipulating its
      flocculability in the microbial growth process.

PMID- 18347793
TI  - Molecular microbial and chemical investigation of the bioremediation of two-phase
      olive mill waste using laboratory-scale bioreactors.
AB  - Two-phase olive mill waste (TPOMW) is a semisolid effluent that is rich in
      contaminating polyphenols and is produced in large amounts by the industry of
      olive oil production. Laboratory-scale bioreactors were used to investigate the
      biodegradation of TPOMW by its indigenous microbiota. The effect of nutrient
      addition (inorganic N and P) and aeration of the bioreactors was studied.
      Microbial changes were investigated by PCR-temperature time gradient
      electrophoresis (TTGE) and following the dynamics of polar lipid fatty acids
      (PLFA). The greatest decrease in the polyphenolic and organic matter contents of
      bioreactors was concomitant with an increase in the PLFA fungal/bacterial ratio.
      Amplicon sequences of nuclear ribosomal internal transcribed spacer region (ITS)
      and 16S rDNA allowed identification of fungal and bacterial types, respectively,
      by comparative DNA sequence analyses. Predominant fungi identified included
      members of the genera Penicillium, Candida, Geotrichum, Pichia, Cladosporium, and
      Aschochyta. A total of 14 bacterial genera were detected, with a dominance of
      organisms that have previously been associated with plant material. Overall, this
      work highlights that indigenous microbiota within the bioreactors through
      stimulation of the fungal fraction, is able to degrade the polyphenolic content
      without the inoculation of specific microorganisms.

PMID- 18347794
TI  - The use of 18F-FDG PET/CT in colorectal liver metastases--comparison with CT and
      liver MRI.
AB  - PURPOSE: We compared 18-fluoro-2-deoxyglucose ((18)F-FDG) positron emission
      tomography-CT (PETCT) with contrast-enhanced whole-body CT (ceCT) in identifying
      extrahepatic disease and with manganese dipyridoxyl diphosphate (Mn-DPDP) liver
      MRI for liver metastases in patients with colorectal liver metastases being
      considered for surgery. METHODS: Sixty-five patients (median age 65 years; 42
      men) with colorectal cancer and known or suspicious liver metastases and who
      underwent a PETCT, ceCT and Mn-DPDP MRI were identified. Results were
      retrospectively reviewed for extrahepatic disease on PETCT and ceCT, and for the
      presence and number of liver metastases on PETCT and Mn-DPDP MRI. Proof of
      metastases was based on histopathology or clinical/imaging follow-up,
      demonstrating disease progression or response. RESULTS: PETCT identified
      unexpected extrahepatic disease not detected on ceCT, leading to change in
      surgical management in 17%. There were three other false-positive cases on PETCT.
      For liver metastases on a per-patient basis, the sensitivity and specificity of
      both PETCT and Mn-DPDP MRI were 98% and 100%, respectively. On a per-lesion
      basis, PETCT and MRI were discordant in 15% (10/66 scans). MRI correctly
      identified more sub-centimeter metastases in eight scans. PETCT correctly
      identified more metastases in one case and confirmed disease in one equivocal
      MRI. CONCLUSION: PETCT has incremental benefit over conventional ceCT in
      identifying extrahepatic disease in metastatic colorectal cancer. PETCT has high
      sensitivity and specificity for the presence of liver metastases and should be
      included early in initial pre-surgical evaluation and could potentially guide the
      use of Mn-DPDP MRI. However, Mn-DPDP MRI is superior for small liver metastases
      and remains a prerequisite for surgical planning in patients with confined liver
      metastases.

PMID- 18347795
TI  - Preclinical discovery of ixabepilone, a highly active antineoplastic agent.
AB  - The epothilones and their analogs constitute a novel class of antineoplastic
      agents, produced by the myxobacterium Sorangium cellulosum. These antimicrotubule
      agents act in a similar manner to taxanes, stabilizing microtubules and resulting
      in arrested tumor cell division and apoptosis. Unlike taxanes, however,
      epothilones and their analogs are macrolide antibiotics, with a distinct tubulin
      binding mode and reduced susceptibility to a range of common tumor resistance
      mechanisms that limit the effectiveness of taxanes and anthracyclines. While
      natural epothilones A and B show potent antineoplastic activity in vitro, these
      effects were not seen in preclinical in vivo models due to their poor metabolic
      stability and unfavorable pharmacokinetics. A range of epothilone analogs was
      synthesized, therefore, with the aim of identifying those with more favorable
      characteristics. Here, we describe the preclinical characterization and selection
      of ixabepilone, a semi-synthetic epothilone B analog, among many other epothilone
      analogs. Ixabepilone demonstrated superior preclinical characteristics, including
      high metabolic stability, low plasma protein binding and low susceptibility to
      multidrug resistance protein-mediated efflux, all of which were predictive of
      potent in vivo cell-killing activity. Ixabepilone also demonstrated in vivo
      antitumor activity in a range of human tumor models, several of which displayed
      resistance to commonly used agents such as anthracyclines and taxanes. These
      favorable preclinical characteristics have since translated to the clinic.
      Ixabepilone has shown promising phase II clinical efficacy and acceptable
      tolerability in a wide range of cancers, including heavily pretreated and drug
      resistant tumors. Based on these results, a randomized phase III trial was
      conducted in anthracycline-pretreated or resistant and taxane-resistant
      metastatic breast cancer to evaluate ixabepilone in combination with
      capecitabine. Ixabepilone combination therapy showed significantly superior
      progression-free survival and tumor responses over capecitabine alone.

PMID- 18347796
TI  - Computing likelihoods for coalescents with multiple collisions in the infinitely
      many sites model.
AB  - One of the central problems in mathematical genetics is the inference of
      evolutionary parameters of a population (such as the mutation rate) based on the
      observed genetic types in a finite DNA sample. If the population model under
      consideration is in the domain of attraction of the classical Fleming-Viot
      process, such as the Wright-Fisher- or the Moran model, then the standard means
      to describe its genealogy is Kingman's coalescent. For this coalescent process,
      powerful inference methods are well-established. An important feature of the
      above class of models is, roughly speaking, that the number of offspring of each
      individual is small when compared to the total population size, and hence all
      ancestral collisions are binary only. Recently, more general population models
      have been studied, in particular in the domain of attraction of so-called
      generalised Lambda-Fleming-Viot processes, as well as their (dual) genealogies,
      given by the so-called Lambda-coalescents, which allow multiple collisions.
      Moreover, Eldon and Wakeley (Genetics 172:2621-2633, 2006) provide evidence that
      such more general coalescents might actually be more adequate to describe real
      populations with extreme reproductive behaviour, in particular many marine
      species. In this paper, we extend methods of Ethier and Griffiths (Ann Probab
      15(2):515-545, 1987) and Griffiths and Tavare (Theor Pop Biol 46:131-159, 1994a,
      Stat Sci 9:307-319, 1994b, Philos Trans Roy Soc Lond Ser B 344:403-410, 1994c,
      Math Biosci 12:77-98, 1995) to obtain a likelihood based inference method for
      general Lambda-coalescents. In particular, we obtain a method to compute
      (approximate) likelihood surfaces for the observed type probabilities of a given
      sample. We argue that within the (vast) family of Lambda-coalescents, the
      parametrisable sub-family of Beta(2 - alpha, alpha)-coalescents, where alpha in
      (1, 2], are of particular relevance. We illustrate our method using simulated
      datasets, thus obtaining maximum-likelihood estimators of mutation and
      demographic parameters.

PMID- 18347797
TI  - Continuous versus pulse harvesting for population models in constant and variable
      environment.
AB  - We consider both autonomous and nonautonomous population models subject to either
      impulsive or continuous harvesting. It is demonstrated in the paper that the
      impulsive strategy can be as good as the continuous one, but cannot outperform
      it. We introduce a model, where certain harm to the population is incorporated in
      each harvesting event, and study it for the logistic and the Gompertz laws of
      growth. In this case, impulsive harvesting is not only the optimal strategy but
      is the only possible one.

PMID- 18347798
TI  - Repeat induced point mutation in two asexual fungi, Aspergillus niger and
      Penicillium chrysogenum.
AB  - Repeat induced point mutation (RIP) is a gene silencing mechanism present in
      fungal genomes. During RIP, duplicated sequences are efficiently and irreversibly
      mutated by transitions from C:G to T:A. For the first time, we have identified
      traces of RIP in transposable elements of Aspergillus niger and Penicillium
      chrysogenum, two biotechnologically relevant fungi. We found that RIP in P.
      chrysogenum has affected a large set of sequences, which also contain other
      mutations. On the other hand, RIP in A. niger is limited to only few sequences,
      but literally all mutations are RIP-like. Surprisingly, RIP occurred only in
      transposon sequences that have disrupted open reading frames in A. niger, a
      phenomenon not yet reported for other fungi. In both fungal species, we
      identified two sequences with strong sequence similarity to Neurospora crassa
      RID. RID is a putative DNA methyltransferase and the only known enzyme involved
      in the RIP process. Our findings suggest that both A. niger and P. chrysogenum
      either had a sexual past or have a sexual potential. These findings have
      important implications for future strain development of these fungi.

PMID- 18347799
TI  - Complex regional pain syndrome (CPRS type I) after a burn injury of the hand.
AB  - Complex regional pain syndrome (CRPS) type I is a clinical condition
      characterized by persistent pain in one part or the entire extremity after a
      minor trauma, fracture, or after an operation which does not involve nerve damage
      and/or sympathetic hyperactivity. Despite large-scale studies on the
      complications that arise after burns, literature reveals few reports on
      neurological problems and CRPS developing after burns. It is a rare complication
      of a burn injury to an extremity. Its early signs and symptoms are similar to
      those of burn wound itself. This study describes an unusual cause of complex
      regional pain syndrome in burn patients. The report highlights physical
      examination findings, the new diagnostic criteria of complex regional pain
      syndrome, and difficulties in diagnosis.

PMID- 18347800
TI  - Chromosomal DNA content of sweet pepper determined by association of cytogenetic
      and cytometric tools.
AB  - The nuclear DNA content of sweet pepper (Capsicum annuum L. var. annuum, 2n = 24)
      has been measured by flow and image cytometries but the DNA content of each
      chromosome of this species has not yet been regarded. DNA content of individual
      chromosomes has been quantified by the flow karyotyping technique, which requires
      a great quantity of intact metaphasic chromosomes and methods that allow the
      characterization of individual chromosomes; however, the obtainment of adequate
      number of metaphases can be difficult in some species like C. annuum. In order to
      estimate the DNA content of each C. annuum var. annuum cv. "New Mexican"
      chromosome, flow and image cytometries were associated with the cytogenetic
      methodology. First, the DNA amount (2C = 6.90 pg) was established by flow
      cytometry. Integrated optical density (IOD) values were calculated by image
      cytometry for each Feulgen stained metaphasic chromosome. Then, by distributing
      the correspondent metaphasic value (4C = 13.80 pg) proportionally to average IOD
      values, the following chromosomal DNA contents were obtained in pg: 0.74
      (chromosome 1), 0.67 (2), 0.61 (3, 4), 0.60 (5), 0.59 (6, 7), 0.58 (8), 0.57 (9),
      0.56 (10) and 0.39 (11, 12). This study reports an alternative and reproducible
      technique that makes quantifying the chromosomal DNA content possible.

PMID- 18347801
TI  - Hypocotyl-based Agrobacterium-mediated transformation of soybean (Glycine max)
      and application for RNA interference.
AB  - An efficient system of gene transformation is necessary for soybean [Glycine max
      (L.) Merrill] functional genomics and gene modification by using RNA interference
      (RNAi) technology. To establish such system, we improved the conditions of tissue
      culture and transformation for increasing the frequency of adventitious shoots
      and decreasing the browning and necrosis of hypocotyls. Adding N(6)
      benzylaminopurine (BAP) and silver nitrate in culture medium enhanced the shoot
      formation on hypocotyls. BAP increased the frequency of the hypocotyls containing
      adventitious shoots, while silver nitrate increased the number of shoots on the
      hypocotyls. As a result, the number of adventitious shoots on hypocotyls cultured
      in medium containing both BAP and silver nitrate was 5-fold higher than the
      controls. Adding antioxidants in co-cultivation medium resulted in a significant
      decrease in occurrence of browning and necrosis of hypocotyls and increase in
      levels of beta-Glucuronidase (GUS) gene expression. Histochemical assays showed
      that the apical meristem of hypocotyls was the "target tissue" for Agrobacterium
      tumefaciens transformation of soybean. Gene silencing of functional gene by using
      RNAi technology was carried out under above conditions. A silencing construct
      containing an inverted-repeat fragment of the GmFAD2 gene was introduced into
      soybean by using the A. tumefaciens-mediated transformation. Several lines with
      high oleic acid were obtained, in which mean oleic acid content ranged from 71.5
      to 81.9%. Our study demonstrates that this transgenic approach could be
      efficiently used to improve soybean quality and productivity through functional
      genomics.

PMID- 18347802
TI  - Inducible expression of Pisum sativum xyloglucan fucosyltransferase in the pea
      root cap meristem, and effects of antisense mRNA expression on root cap cell wall
      structural integrity.
AB  - Mitosis and cell wall synthesis in the legume root cap meristem can be induced
      and synchronized by the nondestructive removal of border cells from the cap
      periphery. Newly synthesized cells can be examined microscopically as they
      differentiate progressively during cap development, and ultimately detach as a
      new population of border cells. This system was used to demonstrate that Pisum
      sativum L. fucosyl transferase (PsFut1) mRNA expression is strongly expressed in
      root meristematic tissues, and is induced >2-fold during a 5-h period when
      mitosis in the root cap meristem is increased. Expression of PsFut1 antisense
      mRNA in pea hairy roots under the control of the CaMV35S promoter, which exhibits
      meristem localized expression in pea root caps, resulted in a 50-60% reduction in
      meristem localized endogenous PsFut1 mRNA expression measured using whole mount
      in situ hybridization. Changes in gross levels of cell wall fucosylated
      xyloglucan were not detected, but altered surface localization patterns were
      detected using whole mount immunolocalization with CCRC-M1, an antibody that
      recognizes fucosylated xyloglucan. Emerging hairy roots expressing antisense
      PsFut1 mRNA appeared normal macroscopically but scanning electron microscopy of
      tissues with altered CCRC-M1 localization patterns revealed wrinkled, collapsed
      cell surfaces. As individual border cells separated from the cap periphery, cell
      death occurred in correlation with extrusion of cellular contents through breaks
      in the wall.

PMID- 18347803
TI  - A local imbalance between MMP and TIMP may have an implication on the severity
      and course of appendicitis.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and the tissue inhibitors of MMPs
      (TIMPs) have been demonstrated to be involved in inflammatory conditions in the
      intestine. The purpose of this study was to investigate whether the alterations
      of the MMP/TIMP balance might reflect the course of the inflammatory process in
      acute appendicitis and if the expression and localisation of MMPs and TIMP is
      variable in the various clinical manifestations of appendicitis. MATERIALS AND
      METHODS: The study comprises 40 patients (26 men and 14 women) having emergency
      appendectomy and a control group constituting of 10 patients (5 men and 5 women)
      having a hemicolectomy for other reasons. MMP and TIMP expressions were assessed
      and compared in tissue specimens from phlegmonous (n = 15), gangrenous (n = 7),
      perforated appendicitis (n = 11) and controls with noninflamed appendices (n =
      10) by means of enzyme-linked immunosorbent assay technique. Localisation of the
      enzymes was performed by immunohistochemistry. RESULTS: MMP-1 was significantly
      higher in gangrenous and perforated appendicitis compared with phlegmonous
      appendicitis and controls (p < 0.05) while MMP-2 was significantly lower in
      gangrenous appendicitis compared with phlegmonous appendicitis and controls. MMP
      2 was also lower in perforated appendicitis when compared with controls (p <
      0.01). Elevated expression of MMP-9 was demonstrated in all groups of
      appendicitis compared with the controls (p < 0.001). CONCLUSIONS: MMP-9 is the
      most abundantly expressed MMP of those investigated in inflamed appendix. We
      postulate that a local imbalance between MMP-9 and TIMP-1 may trigger a
      perforation. These results suggest that MMPs might be useful as biomarkers of
      appendices prone to perforation.

PMID- 18347804
TI  - Twenty-first century brain banking: at the crossroads.
AB  - Brain banks form an increasingly important resource for research. In view of
      declining autopsy rates, brain banks are also gaining importance for medical
      diagnostics, quality control and teaching. In the case of neurodegenerative
      diseases, brain banks have become drivers of discovery and are yielding
      invaluable taxonomic references for neuropathologists. This article provides
      comments on two recent landmark papers in the field (Bell JE et al. Acta
      Neuropathol 2008. doi:10.1007/s00401-008-0358-8; Vonsattel JP et al. Acta
      Neuropathol 2008. doi:10.1007/s00401-007-0311-9). Professionalisation of brain
      banking standards, ethical principles safeguarding the running of a brain bank
      and a proposed code of conduct for brain bank staff are outlined and discussed.
      Special emphasis is placed on the need to enable sustainability of the human
      brain tissue resource in the face of increased financial pressures on medical
      institutions and raised public expectations towards ethical human brain banking
      in a globalised economic environment. It is proposed that brain banks undergo
      rigorous international audit as a prerequisite for their registration with the
      relevant national neuropathological society. This promises to be an important
      safeguard so that proper standards can be assured when tissue is handed out to
      commercial companies. Honesty, accountability and complete transparency are
      mandatory to allow long-lasting success of the brain banking operation by
      guaranteeing that the best possible use is made of the tissue. Preferred access
      by private tissue users must be avoided and money must never be allowed to buy
      access to a brain bank. Since brain banks operate internationally, any mistake
      made may be felt around the globe and could endanger the public's willingness to
      donate brains for research. The much-needed increase in the number of control
      brain donations will only be achievable if broad-based support from the general
      public can be won and maintained.

PMID- 18347805
TI  - Autosomal dominant sensory ataxia: a neuroaxonal dystrophy.
AB  - Autosomal dominant sensory ataxia (ADSA), a rare hereditary ataxia, is
      characterized by progressive dysfunction of central sensory pathways. Its
      pathological features have not been previously documented. We report a case of a
      61-year-old man with ADSA who died of congestive heart failure. Autopsy specimens
      of brain, thoracolumbar spinal cord, peripheral nerve and skeletal muscle were
      examined. There was no abnormality on gross examination. Microscopically, there
      were occasional swollen axons within the cerebral cortex and deep nuclei,
      particularly the subthalamic nucleus, with no neuronal loss, gliosis or
      microglial activation. There were many axonal spheroids within the medulla,
      particularly in the dorsal column nuclei. Axonal spheroids were also seen in the
      dorsal columns and ventral horns in the thoracolumbar spinal cord, but there was
      no Wallerian degeneration or demyelination. Amyloid precursor protein (APP)
      immunostaining of some of the spheroids suggested continuing dysfunction of
      axoplasmic flow in some regions. There was mild inflammation of peripheral nerve
      roots but no spheroid, and patchy chronic inflammation of skeletal muscle. In
      summary, the major pathological process in ADSA is a neuroaxonal dystrophy most
      prominent in the dorsal columns and dorsal column nuclei, consistent with the
      clinical pattern of central sensory pathway degeneration.

PMID- 18347806
TI  - Acetabular reinforcement ring in primary total hip arthroplasty: a minimum 10
      year follow-up.
AB  - INTRODUCTION: We report the results of a titanium acetabular reinforcement ring
      with a hook (ARRH) in primary total hip arthroplasty (THA), which was introduced
      in 1987 and continues to be used routinely in our center. The favorable results
      of this device in arthroplasty for developmental dysplasia and difficult
      revisions motivated its use in primary THA. With this implant only minimal
      acetabular reaming is necessary, anatomic positioning is achieved by placing the
      hook around the teardrop and a homogenous base for cementing the polyethylene cup
      is provided. MATERIALS AND METHODS: Between April 1987 and December 1991, 241
      THAs with insertion of an ARRH were performed in 178 unselected, consecutive
      patients (average age 58 years; range 30-84 years) with a secondary
      osteoarthrosis in 41% of the cases. RESULTS: At the time of the latest follow-up,
      33 patients (39 hips) had died and 17 cases had been lost to follow-up. The
      median follow-up was 122 months with a minimum of 10 years. Eight hips had been
      revised, leaving 177 hips in 120 living patients without revision. Six cups were
      revised because of aseptic loosening. Two hips were revised for sepsis. The mean
      Merle d'Aubigne score for the remaining hips was 16 (range 7-18) at the latest
      follow-up. For aseptic loosening, the probability of survival of the cup was 0.97
      (95% confidence interval, 0.94-0.99). However, analysis of radiographs implied
      loosening in seven other cups without clinical symptoms. CONCLUSIONS: The results
      of primary THA using an acetabular reinforcement ring parallel the excellent
      results of these implants often observed in difficult primary and revision
      arthroplasty at a minimum of 10 years. Survivorship is comparable to modern
      cementless implants. Medial migration that occurs with loosening of the
      acetabular component seems to be prevented with this implant. Radiographic
      loosening signs can exist without clinical symptoms.

PMID- 18347807
TI  - Double-level posterior spinal shortening for paralytic osteoporotic vertebral
      collapse of two vertebral bodies with a normal vertebra in between: a case
      report.
AB  - INTRODUCTION: Spinal shortening is indicated for osteoporotic vertebral collapse.
      However, this surgical procedure has not been indicated for more than two
      vertebral levels that are not adjacent. We experienced a rare case of paraparesis
      due to osteoporotic vertebral collapse of two vertebral bodies with a normal
      vertebra in between and treated successfully by the double-level posterior
      shortening procedure. MATERIALS AND METHODS: A 79-year-old woman suffered from
      delayed paraparesis 2 years after L1 and Th11 vertebral body compression
      fracture. Plain X-ray photographs showed Th11 and L1 vertebral body collapse, Th7
      compression fracture and a kyphosis angle of 30 degrees from Th10 to L2. Plain
      magnetic resonance imaging showed spinal canal stenosis at Th11 and L1 vertebral
      body levels. She was treated by double-level posterior spinal shortening using
      pedicle screw and hook systems. RESULTS: After the procedure, the patient's
      kyphosis angle decreased to 10 degrees and her back pain, leg pain, and sensory
      deficits improved. She was able to walk by herself. Although new vertebral
      compression fractures occurred at L4 and L5 in the follow-up period, there has
      been no deterioration of the neurological symptoms 5 years after the operation.
      CONCLUSION: Delayed paraparesis after double-level thoracolumbar vertebral
      collapse due to osteoporosis was treated successfully by double-level posterior
      spinal shortening using a pedicle screw and hook system.

PMID- 18347808
TI  - Recurrent mutation in keratin 17 in a large family with pachyonychia congenita
      type 2.

PMID- 18347809
TI  - Ex vivo evaluation of force data and tissue elasticity for robot-assisted FESS.
AB  - The objective of this study was to describe and evaluate soft tissue and bone
      properties of nasal cavity and paranasal sinuses in ex vivo preparations for a
      safe robot-assisted endoscope movement during functional endoscopic sinus surgery
      (FESS). In a first experiment we measured forces exerted by the endoscope during
      FESS with a force/torque sensor. In a second experiment we used a purpose built
      device to exert forces on chosen tissue structures. The experiment was monitored
      by a custom software, which records force of the endoscope and the deformation
      and the breaking point of tissue. All tests were performed on five formalin fixed
      cadaver heads. In the first experiment we found that the average force during
      FESS is 2.21 N and the maximal force is 7.96 N. The force-way-ratio measurement
      shows highest elasticity for the ethmoidal bulla, followed by the lamina
      papyracea; however, they break at low forces (> or =6 N). Furthermore the carotid
      canal seems to have the lowest elasticity but it can tolerate forces up to 30 N.
      Based on these measurements force thresholds can be defined for robot-assisted
      endoscope guidance. All thresholds have to be assigned to subregions of the nasal
      cavity and paranasal sinuses.

PMID- 18347810
TI  - UPPP combined with radiofrequency thermotherapy of the tongue base for the
      treatment of obstructive sleep apnea syndrome.
AB  - We investigated the outcome of uvulopalatopharyngoplasty (UPPP) combined with
      radiofrequency thermotherapy of the tongue base (RFTB) in patients with
      obstructive sleep apnea syndrome (OSAS) with both palatal and retroglossal
      obstruction, and we compared these results with the results of single level
      surgery (UPPP). A retrospective cohort study was performed in patients with mild
      to severe OSAS who underwent UPPP with or without RFTB. Seventy-five patients
      with both palatal and retroglossal obstruction underwent UPPP, 38 patients
      without RFTB (group 1) and 37 patients with RFTB (group 2). The outcome of the
      surgery was measured by both objective success (defined as a reduction of AHI
      >50% and AHI below 20) and subjective improvement. In group 1 the overall success
      rate was 42%, and in group 2 49%. Other polysomnographic values (AI, DI, mean
      SaO2) improved after surgery (not significant). No serious adverse events
      occurred. Surgical treatment of combined palatal and retroglossal obstruction
      remains a challenge. Adding RFTB to UPPP results in a mild improvement compared
      to UPPP alone. Although the addition of RFTB to UPPP seems to result in only a
      limited improvement, there is no major downside to it. RFTB is well tolerated and
      safe.

PMID- 18347811
TI  - An unusual complication of umbilical catheterisation.
AB  - We report the first case of perforated Meckel's diverticulum in a 1-day-old pre
      term infant as a consequence of umbilical vein catheterisation. The clinical
      course consisted of abdominal distension and pneumoperitoneum that occurred after
      12 h of life. Perforated Meckel's diverticulum was found at laparotomy. Neither
      inflammatory phenomena nor ectopic mucosa were found at microscopical
      examination. Perforation of the diverticulum was a complication of umbilical
      catheter insertion through a narrow lumen in the umbilical cord mistaken for an
      umbilical vein and connected to Meckel's diverticulum through a very short
      fibrous band. A search of the literature did not reveal any similar cases.

PMID- 18347812
TI  - Baseline elevated leukocyte count in peripheral blood is associated with poor
      survival in patients with advanced non-small cell lung cancer: a prognostic
      model.
AB  - PURPOSE: We aimed to investigate the prognostic significance of several baseline
      variables in stage IIIB-IV non-small cell lung cancer to create a model based on
      independent prognostic factors. METHODS/RESULTS: A total of 320 patients were
      treated with last generation chemotherapy regimens. The majority of patients
      received treatment with cisplatin + gemcitabine or gemcitabine alone if older
      than 70 years or with an ECOG performance status (PS) = 2. Performance status of
      2, squamous histology, number of metastatic sites >2, presence of bone, brain,
      liver and contralateral lung metastases and elevated leukocyte count in
      peripheral blood were all statistically significant prognostic factors in
      univariate analyses whereas the other tested variables (sex, stage, age, presence
      of adrenal gland and skin metastases) were not. Subsequently, a multivariate
      Cox's regression analysis identified PS 2 (P < 0.001, hazard ratio 2.57),
      elevated leukocyte count (P < 0.001, hazard ratio 1.79), squamous histology (P =
      0.005, hazard ratio 1.45) and presence of brain metastases (P = 0.035, hazard
      ratio 1.5) as independent prognostic factors for poor survival. Patients were
      assigned to one of three risk groups according to the cumulative risk defined as
      the sum of simplified risk scores of the four independent prognostic factors. Low
      , intermediate- and high-risk patients achieved a median survival of 10.2 months
      (95% confidence interval (CI) 8.9-11.6), 5.1 months (95% CI 4.0-6.2) and 2.8
      months (95% CI 0.5-5.2), respectively. The high-risk group encompassed PS 2
      patients with two or three adjunctive unfavourable independent prognostic
      factors. CONCLUSIONS: Performance status, white blood cells count, histology and
      brain metastases resulted in our series prognostic factors of survival in NSCLC
      patients treated with chemotherapy at a multivariate analysis. Leukocyte count
      resulted the stronger factor after performance status. If prospectly validated,
      the proposed prognostic model could be useful to stratify performance status 2
      patients in specific future trials.

PMID- 18347813
TI  - Tamoxifen for salivary gland adenoid cystic carcinoma: report of two cases.
AB  - PURPOSE: Adenoid cystic carcinoma of the salivary gland (ACC-SG) is a slow
      growing tumor that is refractory to most chemotherapeutic agents. Estrogen
      receptor (ER) antagonists provide a novel approach for recurrent disease.
      METHODS: We report two cases of ACC-SC in which Tamoxifen/Toremifene were used.
      RESULTS: Both patients obtained long-term stability of disease with no associated
      toxicity. CONCLUSIONS: Given the relatively unsuccessful treatments for ACC-SC
      and the low toxicity of ER antagonists, such therapy should be considered in
      these patients for its potential disease-stabilizing effects.

PMID- 18347814
TI  - B7-H1 up-regulated expression in human pancreatic carcinoma tissue associates
      with tumor progression.
AB  - PURPOSE: Aberrant tumor cell B7-H1 expression, a member of B7 family that can
      predominantly stimulate interleukin 10 (IL-10) products, contributed to the tumor
      immune evasion and tumor progression. This study was designed to investigate the
      expression of B7-H1 and IL-10 in normal pancreas tissues and pancreatic carcinoma
      samples, and to evaluate clinical significance of B7-H1 expression in pancreatic
      carcinoma. METHODS: First, the B7-H1 and IL-10 expression in 40 pancreatic
      carcinoma samples and 8 healthy pancreas specimens using reverse transcription
      PCR (RT-PCR) and western-blotting was detected. Localization of B7-H1 and IL-10
      was confirmed by immunohistochemical (IHC) staining. Next, the association
      between B7-H1 expression and tumor differentiation and tumor stage was analyzed.
      Finally, the correlation between tumor-associated B7-H1 and IL-10 was evaluated.
      RESULTS: Pancreatic carcinoma samples demonstrated the up-regulated expression of
      B7-H1 and IL-10 at mRNA and protein level compared with normal pancreas tissues.
      IHC staining revealed that B7-H1 and IL-10 was almost localized in tumor cells.
      Analysis of relationship between B7-H1 and tumor clinicopathological
      characteristics showed that B7-H1 expression was significantly associated with
      poor tumor differentiation (P < 0.01) and advanced tumor stage (P < 0.01).
      Meanwhile, tumor-associated B7-H1 expression was also correlated with IL-10
      products (P < 0.01, R (2) = 0.6985, mRNA level; P < 0.01, R (2) = 0.7236, protein
      level) in tumor cells. CONCLUSIONS: Our findings for the first time demonstrated
      up-regulated B7-H1 expression in human pancreatic carcinoma tissues, which might
      play a role in tumor progression and invasiveness. This expression seemed to be
      related to the ability of B7-H1 to promoting IL-10 secretion.

PMID- 18347815
TI  - Effects of environmental stress on intertidal mussels and their sea star
      predators.
AB  - Consumer stress models of ecological theory predict that predators are more
      susceptible to stress than their prey. Intertidal mussels, Mytilus californianus,
      span a vertical stress gradient from the low zone (lower stress) to the high zone
      (higher thermal and desiccation stress), while their sea star predators, Pisaster
      ochraceus, range from the low zone only into the lower edge of the mussel zone.
      In summer 2003, we tested the responses of sea stars and mussels to environmental
      stress in an experiment conducted on the Oregon coast. Mussels were transplanted
      from the middle of the mussel bed to cages in the low and high edges of the
      mussel bed. Sea star predators were added to half of the mussel cages. Mussels
      and sea stars were sampled between June and August for indicators of sublethal
      stress. Mussel growth was measured, and tissues were collected for heat shock
      protein (Hsp70) analyses and histological analyses of reproduction. Sea stars
      were weighed, and tissues were sampled for Hsp70 analyses. Mussels in high-edge
      cages had higher levels of total Hsp70 and exhibited spawning activity earlier in
      the summer than mussels in the low-edge cages. Sea stars suffered high mortality
      in the high edge, and low-edge sea stars lost weight but showed no differences in
      Hsp70 production. These results suggest that stress in the intertidal zone
      affected the mobile predator more than its sessile prey, which is consistent with
      predictions of consumer stress models.

PMID- 18347816
TI  - Nitrogen preferences and plant-soil feedbacks as influenced by neighbors in the
      alpine tundra.
AB  - Plant resource partitioning of chemical forms of nitrogen (N) may be an important
      factor promoting species coexistence in N-limited ecosystems. Since the microbial
      community regulates N-form transformations, plant partitioning of N may be
      related to plant-soil feedbacks. We conducted a (15)N tracer addition experiment
      to study the ability of two alpine plant species, Acomastylis rossii and
      Deschampsia caespitosa, to partition organic and inorganic forms of N. The
      species are codominant and associated with strong plant-soil feedbacks that
      affect N cycling. We manipulated interspecific interactions by removing
      Acomastylis or Deschampsia from areas where the species were codominant to test
      if N uptake patterns varied in the presence of the other species. We found that
      Deschampsia acquired organic and inorganic N more rapidly than Acomastylis,
      regardless of neighbor treatment. Plant N uptake-specifically ammonium uptake
      increased with plant density and the presence of an interspecific neighbor.
      Interestingly, this change in N uptake was not in the expected direction to
      reduce niche overlap and instead suggested facilitation of ammonium use. To test
      if N acquisition patterns were consistent with plant-soil feedbacks, we also
      compared microbial rhizosphere extracellular enzyme activity in patches dominated
      by one or the other species and in areas where they grew together. The presence
      of both species was generally associated with increased rhizosphere extracellular
      enzyme activity (five of ten enzymes) and a trend towards increased foliar N
      concentrations. Taken together, these results suggest that feedbacks through the
      microbial community, either in response to increased plant density or specific
      plant neighbors, could facilitate coexistence. However, coexistence is promoted
      via enhanced resource uptake rather than reduced niche overlap. The importance of
      resource partitioning to reduce the intensity of competitive interactions might
      vary across systems, particularly as a function of plant-soil feedbacks.

PMID- 18347817
TI  - Early spring leaf out enhances growth and survival of saplings in a temperate
      deciduous forest.
AB  - Saplings of many canopy tree species in winter deciduous forests receive the
      major portion of their light budget for their growing season prior to canopy
      closure in the spring. This period of high light may be critical for achieving a
      positive carbon (C) gain, thus contributing strongly to their growth and
      survival. This study of saplings of Aesculus glabra and Acer saccharum in
      Trelease Woods, Illinois, USA, tested this hypothesis experimentally by placing
      tents of shade cloth over saplings during their spring period of high light prior
      to canopy closure in three consecutive years. Leaf senescence began 16 days (year
      0) and 60 days (year 1) earlier for shaded A. glabra saplings than control
      saplings. No change in senescence occurred for A. saccharum. The annual absolute
      growth in stem diameter of both species was negligible or negative for shaded
      saplings, but positive for control saplings. Only 7% of the shaded A. glabra
      saplings were alive after 2 years, while all control saplings survived for 3
      years; only 20% of the shaded A. saccharum saplings survived for 3 years, while
      73% of control saplings were alive after the same period. Early spring leaf out
      is a critical mechanism that allows the long-term persistence of saplings of
      these species in this winter deciduous forest. Studies and models of C gain,
      growth, and survival of saplings in deciduous forests may need to take into
      account their spring phenology because saplings of many species are actually
      "sun" individuals in the spring prior to their longer period in the summer shade.

PMID- 18347818
TI  - Fermentation of acid hydrolysates from olive-tree pruning debris by Pachysolen
      tannophilus.
AB  - The influence of the type and concentration of acid in the hydrolysis process and
      its effect on the subsequent fermentation by Pachysolen tannophilus (ATCC 32691)
      to produce ethanol and xylitol was studied. The hydrolysis experiments were
      performed using hydrochloric, sulphuric and trifluoroacetic acids in
      concentrations ranging from 0.1 to 1.0 N, a temperature of 90 degrees C, and a
      time of 240 min. The fermentation experiments were conducted on a laboratory
      scale in a batch-culture reactor at pH 4.5 and 30 degrees C. The hydrolysis with
      the highest acid concentration produced the complete solubilization of
      hemicellulose to monosaccharides. The highest values for the specific rate of
      ethanol production were registered in cultures hydrolyzed with trifluoroacetic
      acid, and values were found to decrease as the acid concentration increased. The
      highest values of overall ethanol yields (Y(E/s)G = 0.37 kg kg(-1)) were also
      found in the fermentation of the hydrolysates of trifluoroacetic acid.

PMID- 18347819
TI  - Health behaviors of Australian colorectal cancer survivors, compared with
      noncancer population controls.
AB  - GOAL: A better understanding of health behaviors after a cancer diagnosis is
      important, as these behaviors are related to physical functioning, disease
      recurrence, development of second primary cancers, and risk of other chronic
      diseases. Body weight and health behaviors (smoking status, alcohol consumption,
      and physical activity) were examined in a population-based sample of colorectal
      cancer survivors and compared to a matched population group. MATERIALS AND
      METHODS: Data were collected by telephone interviews pre-diagnosis
      (retrospectively reported), 6 and 12 months post-diagnosis for colorectal cancer
      survivors (n = 1,250). Comparison data were from a population-based cancer risk
      survey (n = 6,277). RESULTS: Colorectal cancer survivors were most likely to be
      overweight/obese pre-diagnosis (66%) than at 6 months (54%) or 12 months post
      diagnosis (61%). There was little variation from 6 to 12 months in the proportion
      of current smokers (7% and 8%, respectively) or high-risk drinkers (both 22%).
      The greatest changes were for physical activity, with 53% of survivor's
      sufficiently active pre-diagnosis, 32% at 6 months, and 38% at 12 months post
      diagnosis. At 12 months, colorectal cancer survivors were more likely than the
      comparison group to be: underweight (OR = 2.14, 95% CI = 1.38-3.31); a former
      smoker (OR = 1.44, 95% CI = 1.26-1.63); a low-risk (OR = 1.25, 95% CI = 1.09
      1.44) or high-risk drinker (OR = 1.70, 95% CI = 1.43-2.03); and insufficiently
      active (OR = 1.57, 95% CI = 1.34-1.83) or inactive (OR = 2.76, 95% CI = 2.39
      3.19). However, colorectal cancer survivors were significantly less likely to be
      a current smoker (OR = 0.68, 95% CI = 0.54-0.85). CONCLUSIONS: Our findings show
      particular scope for physical activity interventions for colorectal cancer
      survivors. Improving the general health of cancer survivors should help to
      decrease morbidity in this population and associated health system expenditure.

PMID- 18347820
TI  - Molecular evidence of founder effects of fatal familial insomnia through SNP
      haplotypes around the D178N mutation.
AB  - This work presents a detailed investigation of the genomic region surrounding the
      PRNP gene in a sample of patients diagnosed with fatal familial insomnia (FFI)
      from several European countries, notably Spain. The main focus of the study was
      to explore the origins of the chromosomes carrying the D178N mutation by
      designing a single-nucleotide polymorphism (SNP) haplotype around the PRNP gene.
      Haplotypes were constructed by genotyping six SNPs (rs2756271, rs13040327,
      rs6037932, rs13045348, rs6116474, and rs6116475) in 25 FFI patients from all over
      Spain. To augment the geographical scope of our study, 13 further FFI cases from
      Germany (9) and Italy (4) were also examined. Genotyping of SNPs in conjunction
      with the analysis of genealogical data for a group of FFI patients revealed the
      existence of two distinct haplotypes potentially associated with the D178N
      mutation. Of them, GCATTA-M proved to be the common haplotype of Spanish
      patients, whereas ACATTA-M was typical of the German cases. It is interesting to
      note that both haplotypes were identified in the Italian samples: GCATTA-M in a
      family from the Tuscany region and ACATTA-M in a family from the Veneto region.
      Our findings suggest the occurrence of two independent D178N-129M mutational
      events in Europe, preserved and transmitted from one generation to the next until
      nowadays. Likewise, results based on the analysis of SNP data indicate that
      previous hypotheses postulating that the D178N mutation had independent origins
      for each family and that its global distribution was determined by recurrent
      mutational events must be regarded with caution.

PMID- 18347821
TI  - Epidemiologic impact of blood culture practices and antibiotic consumption on
      pneumococcal bacteraemia in children.
AB  - This study examined the roles of two different diagnostic approaches to children
      with fever of unknown origin in determining the patterns of pneumococcal
      bacteraemia in two Spanish regions by comparing their main epidemiologic
      characteristics. Whereas a blood culture is routinely obtained in this setting in
      Navarre, this is not generally the case in Majorca. Additionally, the potential
      role of antibiotic consumption in each region was also analysed. Cumulative
      incidences in children under the age of 14 years were 26.6 per 100,000 child
      years in Navarre (121.1 in children <2 years of age) and 7.3 per 100,000 child
      years in Majorca (33.3 in children <2 years of age). In contrast, the incidences
      per 1,000 blood cultures were similar in both regions. The relative risks of
      occult bacteraemia, bacteraemic pneumonia and meningitis among the children of
      Navarre compared to Majorcan children were 11.8, 2.6 and 0.8, respectively. The
      risk for less virulent (vaccine serotypes plus 6A, 19A and 23A) and for more
      virulent serotypes (1 and 7) was 4.9 and 3.1 times higher in Navarre,
      respectively. The number of 7-valent pneumococcal conjugate vaccine (PCV7) doses
      administered between 2003 and 2004 were also higher in Navarre. Conversely,
      antibiotic resistance and paediatric prescriptions for broad-spectrum antibiotics
      were greater in Majorca. Although the most salient differences between both
      regions, including the effectiveness of pneumococcal conjugate vaccine in
      Navarre, appeared to be confounded by the higher frequency of blood cultures
      taken there, certain differences in serotype composition may be explained by the
      higher antibiotic consumption in Majorca.

PMID- 18347822
TI  - Serogroup distribution and antimicrobial resistance of nasopharyngeal isolates of
      Streptococcus pneumoniae among Beijing children with upper respiratory infections
      (2000-2005).
AB  - The aims of this study were to estimate pneumococcal carriage rate, antimicrobial
      resistance and serogroup distribution of nasopharyngeal isolates of Streptococcus
      pneumoniae among children with acute upper respiratory infections (AURIs) aged 1
      month to 5 years attending outpatient department of the Beijing Children's
      Hospital between 2000 and 2005. Susceptibilities to penicillin, amoxicillin
      clavulanic acid, ceftriaxone, cefuroxime, cefaclor, erythromycin, tetracycline,
      sulfamethoxazole-trimethoprim and chloramphenicol were assessed using the E-test
      and disc diffusion. We also analyzed the correlation between antibiotic
      consumption and rates of resistance. The prevalence of penicillin-nonsusceptible
      pneumococci increased from 26% during 2000-2001 and 21% during 2002-2003 to 31.5%
      in 2004-2005. The percentage of S. pneumoniae resistant to cefaclor and
      cefuroxime increased from about 6% during 2000-2001 to about 23% during 2004-2005
      (P<0.01). The frequency of resistance to erythromycin ranged from 87% to 94%.
      Tetracycline and co-trimoxazole resistance rates were greater than 80%. We
      conclude that resistance rates for most antibiotics are increasing, possibly due
      to misues of antibiotics in the hospital setting. However, chloramphenicol
      resistance was found to decrease, which correlated with the cessation of
      chloramphenicol administration in 1999. Pneumococcal strains (n=519) were
      analyzed by serogroup, and only 296 were found to be seven-valent pneumococcal
      conjugate vaccine-related serotype isolates. This serotype distribution is
      important for surveillance of the new conjugate vaccine.

PMID- 18347823
TI  - Redistributive effects in public health care financing.
AB  - This article focuses on the redistributive effects of different measures to
      finance public health insurance. We analyse the implications of different
      financing options for public health insurance on the redistribution of income
      from good to bad health risks and from high-income to low-income individuals. The
      financing options considered are either income-related (namely income taxes,
      payroll taxes, and indirect taxes), health-related (co-insurance, deductibles,
      and no-claim), or neither (flat fee). We show that governments who treat access
      to health care as a basic right for everyone should consider redistributive
      effects when reforming health care financing.

PMID- 18347824
TI  - Determination of human arterial wall parameters from clinical data.
AB  - This study suggests a method to compute the material parameters for arteries in
      vivo from clinically registered pressure-radius signals. The artery is modelled
      as a hyperelastic, incompressible, thin-walled cylinder and the membrane stresses
      are computed using a strain energy. The material parameters are determined in a
      minimisation process by tuning the membrane stress to the stress obtained by
      enforcing global equilibrium. In addition to the mechanical model, the study also
      suggests a preconditioning of the pressure-radius signal. The preconditioning
      computes an average pressure-radius cycle from all consecutive cycles in the
      registration and removes, or reduces, undesirable disturbances. The effect is a
      robust parameter identification that gives a unique solution. The proposed method
      is tested on clinical data from three human abdominal aortas and the results show
      that the material parameters from the proposed method do not differ significantly
      (p < 0.01) from the corresponding parameters obtained by averaging the result
      from consecutive cycles.

PMID- 18347825
TI  - Activity of abrB310 promoter in wild type and spo0A-deficient strains of
      Clostridium acetobutylicum.
AB  - In Clostridium acetobutylicum, abrB310 is transcribed from two transcription
      start sites (designated A1 and A2) forming an abundant large, and a five- to
      tenfold less abundant small transcript, respectively throughout exponential,
      acidogenic growth and early in the transitional period to stationary,
      solventogenic growth. beta-galactosidase reporter vectors were constructed to
      compare the transcriptional activity of the entire abrB310 promoter and the A1
      and A2 transcription start sites individually. In stark contrast to the primer
      extension data, the A2 start site was threefold more active than the entire
      promoter, which was threefold more active than the A1 start site in wild type C.
      acetobutylicum. The activity expressed from all three reporter vectors declined
      as the cultures transitioned from exponential to stationary growth. In the spo0A
      deficient strain SKO1, reporter vector activity continued for 10 h into
      stationary growth. The removal of the putative Spo0A binding site from all three
      vectors had no significant effect on promoter activity in either wild type or
      SKO1. We conclude that the presence of both the A1 and A2 transcription start
      sites is required for the correct control of abrB310 expression, and that AbrB310
      is necessary but not sufficient for the correct transition between acidogenic and
      solventogenic growth.

PMID- 18347826
TI  - Optimization of medium composition for actinomycin X2 production by Streptomyces
      spp JAU4234 using response surface methodology.
AB  - The effects of cultivation medium compositions including soybean meal, peptone,
      soybean oil and cornstarch for actinomycin X2 production by Streptomyces spp
      JAU4234 were accessed by using response surface methodology. The 2(4) full
      factorial designs and the paths of steepest ascent were effective in searching
      for the major factors of actinomycin X2 production. In this study, cornstarch and
      soybean oil showed negative effect on actinomycin X2 production based on the
      first-order regression coefficients derived from MINITAB software. Subsequently,
      a central composite design for optimization was further investigated. Preliminary
      studies showed that soybean meal and peptone were believed to be the major
      factors for actinomycin X2 production. Estimated optimum compositions for the
      production of actionmycin X2 were as follows (g/l): soybean meal 21.65 and
      peptone 9.41, and result in a maximum actionmycin X2 production of 617.4 mg/l.
      This value was closed to the 612 mg/l actionmycin X2 production from actual
      experimental observations. The yield of actionmycin X2 was increased by 36.9% by
      culturing the strain Streptomyces spp JAU4234 in the nutritionally optimized
      fermentation medium.

PMID- 18347827
TI  - Integrating biological processes to facilitate the generation of 'Biofuel'.

PMID- 18347828
TI  - Diversity in antifungal activity of strains of Chromobacterium violaceum from the
      Brazilian Amazon.
AB  - Chromobacterium violaceum is a free-living Gram-negative bacterium found in soil
      and aquatic habitats; abundantly present in the Brazilian Amazon, it is an
      important example of exploitable microbial diversity of the tropics. In this
      study, 24 strains from the Brazilian Amazon and ATCC 12472(T) were investigated
      for biocontrol potential of seven fungi pathogenic to soybean [Glycine max (L.)
      Merril] seed. Both cells and the supernatants of two Brazilian strains, 07-1 and
      27-1, together with ATCC 12472(T) were strongly antagonistic to six out of the
      seven fungi. The antifungal activity of the Brazilian strains to Fusarium sp.,
      Phomopsis sp. and Cercospora kikuchi was consistently stronger than that of ATCC
      12472(T). In addition, the two Brazilian strains, but not ATCC 12472(T), were
      effective against Corynespora sp., and all three strains and their supernatants
      were equally effective against Aspergillus sp. and Colletotrichum sp. None of the
      strains had antifungal activity against Botroyodiplodia sp. Three potential
      mechanisms related to the antibiosis were investigated: violacein toxicity,
      cyanide production and chitinolytic activity; however, it was not possible to
      associate any of them with the antifungal activity. The results highlight the
      biotechnological potential still to be explored within the poorly characterized
      microbial biodiversity of the tropics.

PMID- 18347829
TI  - Expressions of mass transfer coefficients of bubbles and free surface of culture
      tanks using the k-epsilon turbulence model.
AB  - For mammalian cell culture, getting a continuous supply of oxygen and extracting
      carbon dioxide are primary challenges even in the most modern biopharmaceutical
      manufacturing plants, due to the low oxygen solubility and excessive carbon
      dioxide accumulation. In addition, various independent flow and mass transfer
      characteristics in the culture tanks vessel make scale-up extremely difficult.
      One method for overcoming these and providing rational optimization is solving
      the fluid and mass transport equations by numerical simulation. To develop a
      simulation program, it is decisively important to know mass transfer coefficients
      of gaseous species in the culture tank. In this study, oxygen mass transfer
      coefficients are measured using a beaker with a sparger and impellers. In order
      to investigate the formulation of the mass transfer coefficients, the turbulent
      flow statistics is calculated by a CFD code for all cases, and the expressions of
      the mass transfer coefficients are established as functions of the statistics.
      Until now, the expression by Kawase is known in this field. This expression
      becomes a function only of energy dissipation rate epsilon. It does not coincide
      with the conventional experimental fact that mass transfer coefficient is
      proportional power 0.5 of impeller rotation speed. The new mass transfer
      coefficient is dependent on both of energy dissipation rate epsilon and turbulent
      flow energy k. It satisfies the relation of power of 0.5 of impeller rotation
      speed.

PMID- 18347830
TI  - Plasma detection of NO by a catheter.
AB  - Nitric oxide (NO) released by endothelial cells in response to hemodynamic shear
      stress is a key controller molecule of the vascular functions and antiatherogenic
      mechanisms. Endothelial dysfunction is associated with increased cardiovascular
      events. Therefore, several indirect techniques have been employed to evaluate
      endothelial function or NO bioavailability. However, a growing body of evidences
      suggests limitations of the indirect methods for evaluation of NO
      bioavailability. In years, it has been considered that NO is immediately oxidized
      or inactivated in blood stream. However, recent studies suggest that NO remain
      active in blood stream, causing remote biological response. Therefore, measuring
      plasma NO concentration directly in the circulation will contribute to clarify
      the kinetics and physiological roles of NO and to evaluate endothelial function.
      In this article, the measurement of plasma NO concentration using a newly
      developed catheter-type NO sensor will be described.

PMID- 18347831
TI  - Tensile radial stress in the spinal cord related to arachnoiditis or tethering: a
      numerical model.
AB  - Spinal arachnoiditis comprises fibrous scarring of the subarachnoid space,
      following spinal trauma or inflammation, and is often associated with
      syringomyelia. We hypothesised that cord-to-dura attachments could cause
      transient tensile cord radial stress, as pressure waves propagate. This was
      tested in a fluid-structure interaction model, simulating three types of cord
      tethering, with 'arachnoiditis' confined to a short mid-section of the cord. The
      annular system was excited abdominally with a short transient, and the resulting
      Young and Lamb waves and reflections were analysed. Radial mid-section tethering
      was less significant than axial tethering, which gave rise to tensile radial
      stress locally when the cord was not fixed cranially. Simulated as inextensible
      string connections to the dura, arachnoiditis caused both localised tensile
      radial stress and localised low pressure in the cord as the transient passed. The
      extent of these effects was sensitive to the relative stiffness of the dura and
      cord. Tensile radial stress may create a syrinx in previously normal cord tissue,
      and transiently lowered pressure may draw in interstitial fluid, causing the
      syrinx to enlarge if fluid exit is inhibited. The suggested mechanism could also
      explain the juxtaposition of syrinxes to regions of arachnoiditis.

PMID- 18347832
TI  - Support vector machine for classification of walking conditions using miniature
      kinematic sensors.
AB  - A portable gait analysis and activity-monitoring system for the evaluation of
      activities of daily life could facilitate clinical and research studies. This
      current study developed a small sensor unit comprising an accelerometer and a
      gyroscope in order to detect shank and foot segment motion and orientation during
      different walking conditions. The kinematic data obtained in the pre-swing phase
      were used to classify five walking conditions: stair ascent, stair descent, level
      ground, upslope and downslope. The kinematic data consisted of anterior-posterior
      acceleration and angular velocity measured from the shank and foot segments. A
      machine learning technique known as support vector machine (SVM) was applied to
      classify the walking conditions. SVM was also compared with other machine
      learning methods such as artificial neural network (ANN), radial basis function
      network (RBF) and Bayesian belief network (BBN). The SVM technique was shown to
      have a higher performance in classification than the other three methods. The
      results using SVM showed that stair ascent and stair descent could be
      distinguished from each other and from the other walking conditions with 100%
      accuracy by using a single sensor unit attached to the shank segment. For
      classification results in the five walking conditions, performance improved from
      78% using the kinematic signals from the shank sensor unit to 84% by adding
      signals from the foot sensor unit. The SVM technique with the portable kinematic
      sensor unit could automatically recognize the walking condition for quantitative
      analysis of the activity pattern.

PMID- 18347833
TI  - Slow contractions characterize failing rat hearts.
AB  - The reduced power of the failing heart can be ascribed to a combination of
      reduced force and slower contraction. We hypothesized that these two properties
      are due to different cellular mechanisms. We measured contraction parameters both
      in vivo and in isolated left ventricular (LV) cardiomyocytes from a rat model of
      post infarction congestive heart failure (CHF). ECG was measured simultaneously
      with echocardiography and LV pressure, respectively. Shortening and shortening
      velocity (SV) in isolated cardiomyocytes were measured during different
      stimulation protocols. LV end diastolic pressure (LVEDP) was 24.6 +/- 0.7 mmHg in
      CHF. LV systolic pressure was decreased by 20%, maximum rate of pressure
      development in the LV (+dP/dtmax) by 36% and time in systole increased by 20% in
      CHF compared to sham. Electrical remodelling occurred in CHF cells, which were
      depolarized and had prolonged action potentials (AP) compared to sham cells.
      Fractional shortening (FS) was increased in CHF compared to sham independent of
      stimulation protocol. Larger FS was accompanied by increased sarcoplasmic
      reticulum (SR) Ca2+ load and depended on the electrical remodelling. Time to peak
      contraction (TTP) was increased in CHF compared to sham cells, but in contrast to
      FS, TTP was only slightly affected when the cells were stimulated with sham APs
      and sham diastolic membrane potential (DMP). Contraction duration (corresponding
      to systolic duration) was 25% longer in CHF than in sham independent on
      stimulation protocol. We conclude that electrical remodelling affecting DMP and
      AP duration (APD) significantly affects the size of contraction, whereas the
      mechanism for slowing of contraction in CHF is different.

PMID- 18347834
TI  - Redox signaling triggers protection during the reperfusion rather than the
      ischemic phase of preconditioning.
AB  - In ischemic preconditioning (IPC) brief ischemia/reperfusion renders the heart
      resistant to infarction from any subsequent ischemic insult. Protection results
      from binding of surface receptors by ligands released during the preconditioning
      ischemia. The downstream pathway involves redox signaling as IPC will not protect
      in the presence of a free radical scavenger. To determine when in the IPC
      protocol the redox signaling occurs, seven groups of isolated rabbit hearts were
      studied. All hearts underwent 30 min of coronary branch occlusion and 2 h of
      reperfusion. IPC groups were subjected to 5 min of regional ischemia followed by
      10 min of reperfusion prior to the 30-min coronary occlusion. The Control group
      had only the 30-min occlusion and 2-h reperfusion. In the second group IPC
      preceded the index coronary occlusion. The third group was also preconditioned,
      but the free radical scavenger N-2-mercaptopropionyl glycine (MPG 300 microM) was
      infused during the 10-min reperfusion and therefore was present in the myocardium
      in the distribution of the snared coronary artery during the entire reperfusion
      phase and also during the subsequent 30-min ischemia. In another preconditioned
      group MPG was added to the perfusate before the preconditioning ischemia and
      therefore was present in the tissue only during the preconditioning ischemia and
      then was washed out during reperfusion. In the fifth group MPG was added to the
      perfusate for only the last 5 min of the preconditioning reperfusion and
      therefore was present in the tissue during the last minutes of the reperfusion
      phase and the 30 min of ischemia. In an additional group of IPC hearts MPG was
      infused for only the initial 5 min of the preconditioning reperfusion and then
      allowed to wash out so that the scavenger was present for only the first half of
      the reperfusion phase. Infarct and risk zone sizes were measured by
      triphenyltetrazolium staining and fluorescent microspheres, resp. IPC reduced
      infarct size from 31.3 +/- 2.7% of the ischemic zone in control hearts to only
      8.4 +/- 1.9%. MPG completely blocked IPC's protection in the third (39.4 +/-
      2.8%) and sixth (36.1 +/- 7.7%) groups but did not affect its protection in
      groups 4 (8.1 +/- 1.5%) or 5 (7.8 +/- 1.1%). When deoxygenated buffer was used
      during IPC's reperfusion phase in the seventh group of hearts, protection was
      lost and infarct size was increased over that seen in control hearts (74.5 +/-
      9.0%). Hence redox signaling occurs during the reperfusion phase of IPC, and the
      critical component in that reperfusion phase appears to be molecular oxygen.

PMID- 18347835
TI  - Reduced MMP-2 activity contributes to cardiac fibrosis in experimental diabetic
      cardiomyopathy.
AB  - OBJECTIVE: To evaluate the regulation of matrix metalloproteinase (MMP)-2 in
      diabetic cardiomyopathy. METHODS: Left ventricle (LV) function was determined by
      a micro-tip catheter in streptozotocin (STZ)-induced diabetic rats, 2 or 6 weeks
      (w) after STZ-application. LV total collagen, collagen type I and III content
      were immunohistologically analyzed and quantified by digital image analysis. LV
      collagen type I, III and MMP-2 mRNA expression was quantified by real-time RT
      PCR. LV pro- and active MMP-2 levels were analyzed by zymography; Smad 7,
      membrane type (MT)1-MMP and tissue inhibitor metalloproteinase (TIMP)-2 protein
      levels by Western Blot. RESULTS: STZ-induced diabetes was associated with a time
      dependent impairment of LV diastolic and systolic function. This was paralleled
      by a time-dependent increase in LV total collagen content, despite reduced LV
      collagen type I and III mRNA levels, indicating a role of post
      transcriptional/post-translational changes of extracellular matrix regulation.
      Six weeks (w) after STZ-injection, MMP-2 mRNA expression and pro-MMP-2 levels
      were 2.7-fold (P < 0.005) and 1.3-fold (P < 0.05) reduced versus controls,
      respectively, whereas active MMP-2 was decreased to undetectable levels 6 w post
      STZ. Concomitantly, Smad 7 and TIMP-2 protein levels were 1.3-fold (P < 0.05) and
      10-fold (P < 0.005) increased in diabetics versus controls, respectively, whereas
      the 45 kDa form of MT1-MMP was undetectable in diabetics. CONCLUSION: Under STZ
      diabetic conditions, cardiac fibrosis is associated with a dysregulation in
      extracellular matrix degradation. This condition is featured by reduced MMP-2
      activity, concomitant with increased Smad 7 and TIMP-2 and decreased MT1-MMP
      protein expression, which differs from mechanisms involved in dilated and
      ischemic heart disease.

PMID- 18347836
TI  - Age-dependent endothelial dysfunction is associated with failure to increase
      plasma nitrite in response to exercise.
AB  - Age-dependent alterations of the vessel wall may predispose older individuals to
      increased cardiovascular pathology. Aging is associated with an impaired
      bioactivity of nitric oxide (NO). Plasma nitrite reflects NO-synthase activity
      under fasting conditions and is an important storage pool of NO. To test the
      hypothesis that aging is associated with an impaired capacity of the vasculature
      to increase plasma nitrite during exercise, 29 young and 28 old healthy
      individuals (25 +/- 1 years and 58 +/- 2 years; P < 0.001) without major
      cardiovascular risk factors were enrolled. Exercise stress was similar in both
      groups. Baseline nitrite did not differ (107 +/- 8 vs. 82 +/- 10 nmol/l, young
      vs. old; n.s.) although a trend toward higher nitrite levels in young individuals
      was seen. In young subjects, exercise increased plasma nitrite by 38 +/- 7% (P <
      0.001) compared to only 13 +/- 8% (P = n.s.) in older subjects. L-NMMA blocked
      increases of nitrite. Endothelial function, as defined by flow-mediated-dilation
      (FMD) of the brachial artery via ultrasound, was impaired in older subjects (5.4
      +/- 0.4% vs. 6.7 +/- 0.3%; P < 0.01). Multivariate analysis showed that age (P =
      0.007), BMI (P = 0.010), and LDL (P = 0.021) were independent predictors of
      nitrite increase. The fact that aging is associated with an impaired capacity of
      the vasculature to adequately increase nitrite to physiological stimuli may
      contribute to attenuated maintenance and further deterioration of vascular
      homeostasis with aging.

PMID- 18347837
TI  - No change to grey and white matter volumes in bipolar I disorder patients.
AB  - BACKGROUND: Structural brain imaging is assumed to be a key method to elucidate
      the underlying neuropathology of bipolar disorder. However, magnetic resonance
      imaging studies using region of interest analysis and voxel-based morphometry
      (VBM) revealed quite inconsistent findings. Hence, there is no clear evidence so
      far for core regions of cortical or subcortical structural abnormalities in
      bipolar disorder. The aim of this study was to investigate grey and white matter
      volumes in a large sample of patients with bipolar I disorder. METHODS: Thirty
      five patients with bipolar I disorder and 32 healthy controls matched with
      respect to gender, handedness and education participated in the study. MRI
      scanning was performed and an optimized VBM analysis was conducted. RESULTS: We
      could not observe any significant differences of grey or white matter volumes
      between patients with bipolar disorder and healthy control subjects. Additional
      analyses did not reveal significant correlations between grey or white matter
      volume with number of manic or depressive episodes, duration of illness,
      existence of psychotic symptoms, and treatment with lithium or antipsychotics.
      CONCLUSIONS: With this VBM study we were not able to identify core regions of
      structural abnormalities in bipolar disorder.

PMID- 18347838
TI  - Associations of SNAP-25 polymorphisms with cognitive dysfunctions in Caucasian
      patients with schizophrenia during a brief trail of treatment with atypical
      antipsychotics.
AB  - The synaptosomal-associated protein of 25 kDa (SNAP-25) is part of the soluble N
      ethylmaleimide-sensitive fusion protein (NSF) attachment receptor (SNARE), which
      mediates synaptic neurotransmission. In earlier studies a possible involvement of
      this protein in schizophrenia has been shown. As neurocognitive impairment is a
      core feature in the pathology of schizophrenia and considered to be a putative
      endophenotype according to genetic studies we investigated the influences of
      different SNAP-25 polymorphisms on neuropsychological test results before and
      during treatment with atypical antipsychotics. A total of 104 schizophrenic
      patients treated with atypical antipsychotics were genotyped for three different
      polymorphisms of the SNAP-25 gene (MnlI, TaiI and DdeI in the 3'-UTR). Cognitive
      function was assessed at baseline, week 4 or 6 and week 8 or 12. Results of
      individual neuropsychological tests were assigned to six cognitive domains
      (reaction time and quality; executive function; working, verbal and visual
      memory) and a general cognitive index. The MnlI and TaiI polymorphisms showed no
      associations to deficits on neuropsychological test results. In contrast, we
      observed a significant relation between the DdeI polymorphism of the SNAP-25 gene
      and cognitive dysfunctions. Homozygote T/T allele carriers of the DdeI
      polymorphism showed significant better neuropsychological test results in
      cognitive domains verbal memory and executive functions than those with the
      combined T/C and C/C genotypes (P < 0.01) at all three time points, but no
      differences in response to treatment with atypical antipsychotics. Additionally,
      TT carriers exhibited significantly better results in a general cognitive index
      (P < 0.05). As we observed an association between the DdeI polymorphism of the
      SNAP-25 gene and cognitive dysfunctions of schizophrenic patients our finding
      suggests that the SNAP-25 gene could play a role in the pathophysiology of
      neurocognitive dysfunctions in schizophrenia but is not predictive for treatment
      response with atypical antipsychotics.

PMID- 18347839
TI  - Heavy metals in the nase, Chondrostoma nasus (L. 1758), and its intestinal
      parasite Caryophyllaeus laticeps (Pallas 1781) from Austrian rivers:
      bioindicative aspects.
AB  - Tissue samples from 121 adult specimens of the predominantly herbivorous fish
      species nase, Chondrostoma nasus (L. 1758), from five river sites in Austria were
      analyzed for their metal content. Sediments and water samples of the sites show
      different levels of metal load, with only one site considered being polluted with
      metals. The concentrations of cadmium, copper, lead, and zinc in the tissue of
      the gills, muscle, intestine, and liver of the fish were determined by
      inductively coupled plasma-optical emission spectrometry (ICP-OES). As in one of
      the unpolluted and the polluted river site, a well-established population of the
      tapeworm Caryophyllaeus laticeps (Pallas, 1781) occurred in the intestine of the
      fish; pooled samples of this worm were analysed as well. Both the nase and C.
      laticeps show bioindicative ability for metal pollution in rivers. The results
      allow a more differentiated characterization of the rivers than the sediment
      analyses. Cadmium is found mainly in the liver, with maximum concentrations of
      1.57 microg/g dry weight from unpolluted sites and 5.58 microg/g from the
      polluted site. The highest concentrations of copper are also found in the liver,
      with values between 25 and 333 microg/g. A significantly elevated concentration
      of Cu in the intestine from an "unpolluted" site (mean: 24.06 microg/g) indicates
      an acute pollution in this area at the time of sampling. Lead was found mainly in
      the intestine and liver in concentrations between 0.09 and 4.05 microg/g and 0.26
      and 1.94 microg/g, respectively. In the samples from the polluted site, it also
      could be detected in the gills (mean: 1.38 microg/g). The parasite C. laticeps
      shows different capacities for metal accumulation: Although the concentrations of
      Cu were significantly lower compared to the values of the fish liver, cadmium was
      detected in concentrations up to 5.1 times higher. Lead and zinc concentrations
      were found to be up to 9.7 and 3.0 times higher in the tapeworm compared to the
      fish liver, respectively.

PMID- 18347840
TI  - Reduced fitness of Daphnia magna fed a Bt-transgenic maize variety.
AB  - Genetically modified (GM) maize expressing the Bt-toxin Cry1Ab (Bt-maize) was
      tested for effects on survival, growth, and reproduction of the water flea
      Daphnia magna, a crustacean arthropod commonly used as a model organism in
      ecotoxicological studies. In three repeated experiments, D. magna were fed 100%
      ground maize in suspension, using either GM or isogenic unmodified (UM) maize. D.
      magna fed GM-maize showed a significantly reduced fitness performance: The
      mortality was higher, a lower proportion of females reached sexual maturation,
      and the overall egg production was lower compared to D. magna fed UM isogenic
      maize. We conclude that the tested variety of Bt-maize and its UM counterpart do
      not have the same quality as food sources for this widely used model organism.
      The combination of a reduced fitness performance combined with earlier onset of
      reproduction of D. magna fed Bt-maize indicates a toxic effect rather than a
      lower nutritional value of the GM-maize.

PMID- 18347841
TI  - Effects of river water and salinity on the toxicity of deltamethrin to freshwater
      shrimp, cladoceran, and fish.
AB  - Deltamethrin is a pyrethroid insecticide used extensively to control invertebrate
      pests on cotton and other crops. It is acutely toxic to nontarget aquatic
      organisms, but existing toxicity data are mostly from toxicity tests using
      purified laboratory water that differs greatly from the turbid, high-conductivity
      rivers in the cotton-growing regions of Australia. The aim of this study was to
      determine whether the water quality variables conductivity, suspended particles,
      and dissolved organic matter alter the toxicity of deltamethrin to freshwater
      crustaceans and a fish. We tested three Australian native species: a cladoceran
      (Ceriodaphnia cf. dubia), a freshwater shrimp (Paratya australiensis), and larvae
      of the eastern rainbow fish (Melanotaenia duboulayi). Conductivity of the test
      solutions ranged from 200 to 750 microS/cm, but such changes did not modify the
      toxicity of deltamethrin to any of the test species. However, the toxicity of
      deltamethrin to C. cf. dubia and P. australiensis in river water was
      significantly decreased (1.8-fold to 6.3-fold reduction) compared to that in
      laboratory water. Variability in the toxicity data limited our ability to detect
      differences between laboratory and river water for M. duboulayi. Despite
      reductions in toxicity in natural waters, deltamethrin remained highly toxic [all
      L(E)C(50) values <0.26 microg/L] to all organisms tested; thus, further
      investigation of the hazard of deltamethrin is warranted.

PMID- 18347842
TI  - The reliability of a single pulse oximetry reading as a screening test for
      congenital heart disease in otherwise asymptomatic newborn infants.
AB  - Routine pulse oximetry has been studied to detect children with otherwise
      undiagnosed congenital heart disease prior to nursery discharge. The reported
      sensitivities in asymptomatic patients have been less than expected and vary
      widely, bringing into question the reliability of the test. The purpose of this
      study was to assess whether routine pulse oximetry contributes to identifying
      patients with critical congenital heart disease and to determine the reliability
      of a single pulse oximeter reading in screening asymptomatic newborn infants.
      Between December 26, 2003, and December 31, 2005, three hospitals in west central
      Florida performed a pulse oximetry routinely on all newborns at the time of
      discharge. Patients diagnosed with critical congenital heart disease during the
      study period were identified to assess whether the pulse oximetry reading
      initiated their diagnosis. In one hospital, the pulse oximeter data were
      evaluated for reliability. Downloaded data were compared to a log compiled by the
      nursery personnel, first without (phase 1) and then with (phase 2) their
      knowledge and additional training. Results were characterized as reliable, probe
      placed but reading not verifiable, or no evidence of probe placement. Of the 7962
      infants who received oximetry testing, there were 12 postnatal diagnoses of
      critical congenital heart disease. None was initially identified by routine pulse
      oximetry. Pulse oximetry reliability improved substantially between phase 1 and
      phase 2 (38 v. 60%, p < 0.0001). Optimal reliability (>95%) was obtained by a
      nurse with a degree of LPN or higher performing an assessment of at least 360
      seconds. Routine pulse oximetry was neither reliable nor an important diagnostic
      tool in our cohort. Important human factors (probe placement time, oximetry
      training, and nursing degree) impact single determination pulse oximetry
      reliability. With routine surveillance and quality improvement, the reliability
      of this test can be increased. Future studies to determine the effectiveness of
      pulse oximetry screening for the diagnosis of congenital heart disease in the
      asymptomatic newborn population must address these factors. Until such a study
      demonstrates acceptable sensitivity and clinical value, universal screening
      should not be instituted.

PMID- 18347844
TI  - Selective enhancement of the fluorescent pseudomonad population after amending
      the recirculating nutrient solution of hydroponically grown plants with a
      nitrogen stabilizer.
AB  - Fluorescent pseudomonads have been associated, via diverse mechanisms, with
      suppression of root disease caused by numerous fungal and fungal-like pathogens.
      However, inconsistent performance in disease abatement, after their employment,
      has been a problem. This has been attributed, in part, to the inability of the
      biocontrol bacterium to maintain a critical threshold population necessary for
      sustained biocontrol activity. Our results indicate that a nitrogen stabilizer (N
      Serve, Dow Agrosciences) selectively and significantly enhanced, by two to three
      orders of magnitude, the resident population of fluorescent pseudomonads in the
      amended (i.e., 25 microg ml(-1) nitrapyrin, the active ingredient) and recycled
      nutrient solution used in the cultivation of hydroponically grown gerbera and
      pepper plants. Pseudomonas putida was confirmed as the predominant bacterium
      selectively enhanced. Terminal restriction fragment length polymorphism (T-RFLP)
      analysis of 16S rDNA suggested that N-Serve selectively increased P. putida and
      reduced bacterial diversity 72 h after application. In vitro tests revealed that
      the observed population increases of fluorescent pseudomonads were preceded by an
      early growth suppression of indigenous aerobic heterotrophic bacteria (AHB)
      population. Interestingly, the fluorescent pseudomonad population did not undergo
      this decrease, as shown in competition assays. Xylene and 1,2,4-trimethylbenzene
      (i.e., the inert ingredients in N-Serve) were responsible for a significant
      percentage of the fluorescent pseudomonad population increase. Furthermore, those
      increases were significantly higher when the active ingredient (i.e., nitrapyrin)
      and the inert ingredients were combined, which suggests a synergistic response.
      P. putida strains were screened for the ability to produce antifungal compounds
      and for the antifungal activity against Pythium aphanidermatum and Phytophthora
      capsici. The results of this study suggest the presence of diverse mechanisms
      with disease-suppressing potential. This study demonstrates the possibility of
      using a specific substrate to selectively enhance and maintain desired
      populations of a natural-occurring bacterium such as P. putida, a trait
      considered to have great potential in biocontrol applications for plant
      protection.

PMID- 18347845
TI  - Bacterial diversity of the broadbalk 'classical' winter wheat experiment in
      relation to long-term fertilizer inputs.
AB  - With more than 160 years of contrasting fertilizer regimes, the Broadbalk winter
      wheat experiment represents a unique experimental resource for studying the
      effects of long-term fertilizer application on microbial population diversity.
      Using DGGE and clone library analysis, we report here on eubacterial species
      diversity (16S rRNA gene) and diversity within two sets of gene products
      associated with microbial N acquisition: NifH (nitrogen fixation) and AmtB
      (ammonium transport). Comparisons were made within and between soils treated with
      mineral N fertilizer, farmyard manure or receiving no fertilizer. Analysis of 16S
      rRNA gene DGGE profiles showed no clear patterns to qualitatively distinguish
      bacterial community structure between the three different treatments (P > 0.05),
      with all samples containing a range of eubacterial taxa similar to those that are
      characteristic of soil bacteria reported elsewhere. Intra-plot heterogeneity was
      high and of a similar magnitude to that between treatments. This lack of
      qualitative between plot differences was echoed in the representative sequences
      of 16S rRNA, nifH, and amtB genes in the various samples. Taken together, both
      phylogenetic and functional gene analyses showed bacterial communities in the
      Broadbalk-trial soil were very stable and relatively non-responsive to long-term
      management of balanced fertilizer inputs.

PMID- 18347846
TI  - Elevated lytic phage production as a consequence of particle colonization by a
      marine Flavobacterium (Cellulophaga sp.).
AB  - Bacteria growing on marine particles generally have higher densities and cell
      specific activities than free-living bacteria. Since rapidity of phage adsorption
      is dependent on host density, while infection productivity is a function of host
      physiological status, we hypothesized that marine particles are sites of elevated
      phage production. In the present study, organic-matter-rich agarose beads and a
      marine phage-host pair (Cellulophaga sp., PhiS(M)) were used as a model system to
      examine whether bacterial colonization of particles increases phage production.
      While no production of phages was observed in plain seawater, the presence of
      beads enhanced attachment and growth of bacteria, as well as phage production.
      This was observed because of extensive lysis of bacteria in the presence of beads
      and a subsequent increase in phage abundance both on beads and in the surrounding
      water. After 12 h, extensive phage lysis reduced the density of attached
      bacteria; however, after 32 h, bacterial abundance increased again. Reexposure to
      phages and analyses of bacterial isolates suggested that this regrowth on
      particles was by phage-resistant clones. The present demonstration of elevated
      lytic phage production associated with model particles illustrates not only that
      a marine phage has the ability to successfully infect and lyse surface-attached
      bacteria but also that acquisition of resistance may affect temporal phage-host
      dynamics on particles. These findings from a model system may have relevance to
      the distribution of phage production in environments rich in particulate matter
      (e.g., in coastal areas or during phytoplankton blooms) where a significant part
      of phage production may be directly linked to these nutrient-rich "hot spots."

PMID- 18347848
TI  - Future of plastic surgery.

PMID- 18347847
TI  - Genetic and functional diversity among fluorescent pseudomonads isolated from the
      rhizosphere of banana.
AB  - Fluorescent pseudomonads from banana rhizospheric soil were isolated and screened
      for the production of enzymes and hormones such as phosphatase, indole-3-acetic
      acid (IAA), 1-aminocyclopropane-1-carboxylate (ACC) deaminase, protease, and
      antifungal metabolites. Of 95 isolates, 50 (52%) isolates solubilized tri-calcium
      phosphate (TCP), 63 (66%) isolates produced plant growth hormone IAA, 10 (11%)
      isolates exhibited ACC deaminase, and 23 (24%) isolates produced protease.
      Isolates were screened for antifungal activity toward phytopathogenic fungi. Gene
      specific primers have identified the putative antibiotic producing isolates.
      These putative isolates were grown in the production media and production of
      antibiotics was confirmed by thin-layer chromatography (TLC) and high-performance
      liquid chromatography (HPLC). Genotypic analysis by BOX (bacterial repetitive BOX
      element)-polymerase chain reaction (PCR) resulted into three distinct genomic
      clusters at a 50% similarity level and 62 distinct BOX profiles. Based on the
      sequence similarity of 16S rRNA and construction of subsequent phylogenetic tree
      analysis, isolates were designated as Pseudomonas monteilii, P. plecoglossicida,
      P. fluorescens, P. fulva, P. mosselii, P. aeruginosa, P. alcaligenes, and P.
      pseudoalcaligenes. Present study revealed the genetic and functional diversity
      among isolates of fluorescent pseudomonads associated with rhizospheric soil of
      banana and also identified P. monteilii as dominant species. The knowledge on
      genetic and functional diversity of fluorescent pseudomonads associated with
      banana rhizosphere is useful to understand their ecological role and for their
      utilization in sustainable agriculture.

PMID- 18347849
TI  - Value of Multidetector-row Computed Tomography in Diagnosis of Portal Vein
      Invasion by Perihilar Cholangiocarcinoma.
AB  - BACKGROUND: Although knowledge of cancer invasion of the portal bifurcation is
      vitally important in planning an operation for perihilar cholangiocarcinoma, the
      diagnostic capability of multidetector-row computed tomography (MDCT) for this
      purpose has not been assessed. We evaluated how well MDCT could identify cancer
      invasion of the portal bifurcation by perihilar cholangiocarcinoma. METHODS:
      Between April 2003 and June 2005, perihilar cholangiocarcinoma was resected in 87
      patients, 83 of whom underwent MDCT within 1 month before the surgery. Three
      dimensional volume-rendered (3DVR) and multiplanar reformation (MPR) images were
      examined for evidence of portal vein invasion. Agreement with intraoperative and
      pathologic findings was assessed. Portal bifurcation findings by 3DVR and MPR
      were classified into no portal vein stenosis, unilateral stenosis, or more
      extensive stenosis, and also into tumor contact with the bifurcation in no, one
      of two, or two projections. RESULTS: For macroscopic portal vein invasion,
      sensitivity, specificity, positive predictive value, negative predictive value,
      and overall accuracy were 81.5, 91.1, 81.5, 91.1, and 88.0% in 3D portography and
      96.3, 92.6, 86.7, 98.1, and 94.0% in MPR, respectively. Findings by both 3DVR and
      MPR were significantly correlated with depth of cancer invasion (p < 0.001).
      CONCLUSION: MDCT is useful in assessing cancer invasion of the portal vein
      bifurcation by perihilar cholangiocarcinoma.

PMID- 18347850
TI  - Late presentation of intestinal malrotation: an argument for elective repair.
AB  - BACKGROUND: Midgut malrotation most commonly presents in young children. This
      diagnosis is not often entertained in the adolescent or adult with abdominal
      complaints. We reviewed our experience with this subset of malrotation patients.
      METHODS: A retrospective review of medical records from adolescent or adult
      patients identified with a diagnosis of anomaly of intestinal fixation or
      malrotation, who were treated within our health system between 1993 and 2004.
      RESULTS: A total of 33 patients were diagnosed with malrotation and treated with
      Ladd's procedure. Acute abdominal pain was present in 50%, and chronic complaints
      were present in the other patients. Initial work-up included computed tomography
      (CT) scan (28%), upper gastrointestinal (UGI) study (38%), and plain films (47%)
      Postoperative complications occurred more frequently in patients that were
      operated on emergently (60%) than in those that underwent elective surgery (22%;
      p = 0.04). CONCLUSIONS: This large case series of intestinal malrotation in the
      nonpediatric age group suggests that Ladd's procedure can be performed very
      safely. Moreover, the results suggest that patients with known malrotation should
      have Ladd's procedure performed electively rather than urgently.

PMID- 18347851
TI  - Prognostic factors and availability of D2 lymph node dissection for the patients
      with stage II gastric cancer: comparative analysis of subgroups in stage II.
AB  - BACKGROUND: According to the fifth edition of the UICC TNM classification, stage
      II gastric cancer has three subgroups: T1N2M0, T2N1M0, and T3N0M0. This study was
      designed to investigate the prognosis of stage II gastric cancer according to the
      T and N category to verify the accuracy of TNM staging for stage II and to
      determine the prognostic factors for patients with stage II gastric cancer by
      subgroup. METHODS: Clinicopathologic data from 326 patients with stage II gastric
      cancer were studied. We stratified the patients into T2N1 and T3N0 groups and
      performed comparative analysis between the two groups as well as univariate and
      multivariate survival analyses for each group. RESULTS: The five-year survival
      rate for patients with T2N1 disease was 75.6%, whereas for patients with T3N0
      disease it was 68.3%. There was no significant difference in survival between
      T2N1 and T3N0 groups (p = 0.174). Univariate survival analysis showed that age,
      gender, histological type, and the extent of lymph node dissection were
      significant prognostic factors for stage II gastric cancer. However, multivariate
      analysis demonstrated that only gender and the extent of lymph node dissection
      were significant variables. Among these variables, gender was an independent
      prognostic factor for survival only in the T2N1 group. On the other hand, the
      extent of lymph node dissection was an independent prognostic factor in the T3N0
      group, not in the T2N1 group. CONCLUSIONS: There was no significant difference in
      survival between the T2N1 and the T3N0 groups. Thus, our data support the
      accuracy of the TNM staging classification for stage II gastric cancer. We found
      a significant survival benefit with D2 dissection for T3N0 but not T2N1. However,
      before recommending limited lymph node dissection for T2N1 stage disease,
      development of a preoperative method for prediction of depth of invasion and
      lymph node status is needed.

PMID- 18347852
TI  - Arterio-ureteric fistula following iliac angioplasty.
AB  - Arterio-ureteric fistulae are rare but can be associated with significant
      morbidity and mortality. We describe a novel case in which an arterio-ureteric
      fistula occurred as a complication following external iliac artery angioplasty
      and stenting, in a patient who had undergone previous pelvic surgery,
      radiotherapy, ureteric stenting, and urinary diversion surgery. Prompt
      recognition enabled successful endovascular management using a covered stent.

PMID- 18347853
TI  - An easier method for locating replication origins based on real-time polymerase
      chain reaction.
AB  - Locating replication origins (ROs) is an old problem to which diverse answers
      have been previously given. However, a better and more convenient method still
      remains desirable because previously reported methods are time-consuming. In this
      study, we report an easier method for locating ROs based on real-time polymerase
      chain reaction. The feasibility of this method was demonstrated using Escherichia
      coli K-12 and Halobacterium salinarium NRC-1 as models. Our results show that
      this method is easy, fast, and accurate in locating ROs.

PMID- 18347854
TI  - Selection of the internal control gene for real-time quantitative rt-PCR assays
      in temperature treated Leptospira.
AB  - Analysis of gene expression requires sensitive, precise, and reproducible
      measurements for specific mRNA sequences. To avoid bias, real-time RT-PCR is
      referred to one or several internal control genes. Here, we sought to identify a
      gene to be used as normalizer by analyzing three functional distinct housekeeping
      genes (lipL41, flaB, and 16S rRNA) for their expression level and stability in
      temperature treated Leptospira cultures. Leptospira interrogans serovar Hardjo
      subtype Hardjoprajitno was cultured at 30 degrees C for 7 days until a density of
      10(6) cells/ml was reached and then shifted to physiological temperatures (37
      degrees C and 42 degrees C) and to environmental temperatures (25 degrees C and
      30 degrees C) during a 24 h period. cDNA was amplified by quantitative PCR using
      SYBR Green I technology and gene-specific primers for lipL41, flaB, and 16S rRNA.
      Expression stability (M) was assessed by geNorm and Normfinder v.18. 16S rRNA
      registered an average expression stability of M = 1.1816, followed by flaB (M =
      1.682) and lipL41 (M = 1.763). 16S rRNA was identified as the most stable gene
      and can be used as a normalizer, as it showed greater expression stability than
      lipL41 and flaB in the four temperature treatments. Hence, comparisons of gene
      expression will have a higher sensitivity and specificity.

PMID- 18347855
TI  - Visual exposure using single-handed magnet-driven intra-abdominal wireless camera
      in minimal access surgery: is better than 30 degrees endoscope.
AB  - BACKGROUND: The operative field of view in minimal access surgery is constrained
      by the location of the optical port, the direction of view of the endoscope, and
      the limited degrees of freedom of movement of rigid endoscopes through the access
      port. The aim of this study was to examine the feasibility of employing a special
      magnetic setup with a single external handle to fixate, drive, and orientate
      intra-abdominal wireless camera, and compare its visual exposure with that of a
      30 degrees endoscope. METHODS: A wireless magnet-driven camera setup was
      developed comprising a mini wireless camera with integrated white light-emitting
      diodes, a specially constructed base unit for orientation control and smooth
      sliding motion, and an external magnetic handle to fixate and drive the camera
      from the outer surface of the abdominal wall. In a laboratory-based experiment,
      ten subjects with no laparoscopic surgical experience were asked to identify 160
      randomly distributed labels in a trainer box using both a 30 degrees endoscope
      and the wireless camera magnetic setup in a random order. Data were analyzed
      using Student's t-test. RESULTS: The mean (standard deviation) of the number of
      identified labels was higher using the wireless camera magnetic setup 74.8
      (16.96) compared with 30 degrees endoscope 54.7 (12.18); p ? 0.001. However, the
      mean execution time was longer with the camera magnetic system 34.9 (4.4) min
      compared with the 30 degrees endoscope 24.1 (2.8) min; p ? 0.001. CONCLUSION: The
      use of the magnetic wireless camera setup with a single external handle is
      feasible and has demonstrated a wider visual exposure than the 30 degrees
      endoscope.

PMID- 18347856
TI  - The effect of pentoxifylline on oxidative stress in CO2 pneumoperitoneum.
AB  - BACKGROUND: Carbon dioxide (CO(2)) pneumoperitoneum induces peritoneal oxidative
      stress. This experimental, randomized, controlled study was designed to
      investigate the effect of pentoxifylline on oxidative stress induced by CO(2
      )pneumoperitoneum. METHODS: For this study, 36 Swiss albino rats were randomized
      into three groups. Arteria, vena femoralis, and peritoneal cavity were cannulated
      after anesthesia. The arterial pH, partial arterial oxygen pressure (PaO(2)),
      venous PO(2), arterial and venous PO(2) difference (P((a-v))O(2)), serum
      aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), and
      thiobarbituric acid-reactive substances (TBARS) were studied at the end of the
      first and second hours in group 1 (control). In group 2, 1 cc isotonic NaCl was
      injected into peritoneal cavity and then CO(2) pneumoperitoneum was established.
      At the end of the first hour of insufflation and one hour after desufflation, the
      same parameters as in group 1 were studied. In group 3, the CO(2)
      pneumoperitoneum plus pentoxifylline group, all procedures as in group 2 were
      repeated, with the exception of pentoxifylline (50 mg/kg) injected in place of
      saline. RESULTS: At the end of the first hour, P((a-v))O(2 )value in group 2 was
      significantly less than in the control group (group 1) and group 3 (p ? 0.05).
      There were no significant differences in PaO(2, )pH, AST, and ALT values between
      groups (p [ 0.05). TBARS level in group 1 was significantly lower than in the
      other groups, but there was no significant difference in TBARS level between
      groups 2 and 3. At the end of the second hour, TBARS level in group 3 was
      significantly lower than in group 2 (p ? 0.05). CONCLUSIONS: Pentoxifylline may
      reduce the oxidative injury following laparoscopic procedures.

PMID- 18347857
TI  - Obesity should not influence the management of appendicitis.
AB  - BACKGROUND: Obesity implies an adverse effect on outcome after appendectomy. This
      study aimed to determine whether obese patients with appendicitis should be
      managed differently than nonobese patients. METHODS: After appendectomy, all
      patients were enrolled in a prospective clinical pathway and followed from
      initial presentation to full outpatient recovery. RESULTS: In 1 year, 272 adults
      underwent appendectomy, 55 (22%) of whom were obese. The obese patients were
      slightly older (35 vs 33 years; p < 0.001). The time to diagnosis (8.5 vs 8.6 h),
      and the need for computed tomography (CT) scanning (40% vs 49%) was similar in
      both populations. The obese patients had similar rates of perforation (35% vs
      35%) and laparoscopy (47% vs 41%). The median hospital length of stay (LOS) (2
      days) and complications, including wound complications (9.1% vs 10.9%) and
      intraabdominal abscesses (3.6% vs 3.1%), were similar. Subgroup analysis showed a
      longer LOS for the obese patients with perforation than for the nonobese patients
      (6 vs 5.5 days; p = 0.036). CONCLUSION: Obese patients had no greater delay in
      diagnosis, had no greater need for CT scan, gained no additional benefit from
      laparoscopy, and did not incur significantly worse outcomes after appendectomy
      except for an increased LOS among those with perforation.

PMID- 18347858
TI  - Does the extraction-site location in laparoscopic colorectal surgery have an
      impact on incisional hernia rates?
AB  - BACKGROUND: Incisional hernias are a common postoperative complication with
      abdominal surgery. The major risk factors for their development include wound
      infection, obesity, and age. This study aimed to evaluate the impact of
      extraction-site location and technique on incisional hernia rates in laparoscopic
      colorectal surgery. METHODS: A prospective study of 208 consecutive patients who
      underwent laparoscopic colorectal surgery between March 2002 and July 2006 was
      performed. The study included only patients who had an extraction site on the
      abdominal wall. Patients were excluded if they were lost to follow-up evaluation
      or underwent conversion to open procedure. For the 166 patients included in the
      study, the mean follow-up period was 20.2 +/- 14.4 months. Extraction-site
      incisions were classified into two groups: midline or off-midline. Midline wounds
      involved sharp division of the linea alba and were closed with a single layer of
      no.1 Vicryl. Off-midline incisions involved sharp division of the anterior and
      posterior sheaths with blunt spreading of the muscular layers and were closed in
      two layers with no. 1 Vicryl. Risk factors including wound infection, body mass
      index (BMI), age, and diabetes were analyzed. RESULTS: The incisional hernia rate
      for the entire series was 7.8%. The incisional hernia rate was 17.6% for the
      midline group (n = 74) and 0% for the off-midline group (n = 92) (p = 0.0002,
      statistically significant). There was no statistically significant difference in
      age, BMI, diabetes, follow-up time, or wound infection rate between the two
      groups. CONCLUSION: In this series, the midline extraction site resulted in a
      significantly higher incisional hernia rate statistically than the off-midline
      extraction sites. The authors therefore have adopted an off-midline blunt muscle
      splitting extraction site when performing laparoscopic colorectal surgery.

PMID- 18347859
TI  - Time-efficient laparoscopic skills assessment using an augmented-reality
      simulator.
AB  - BACKGROUND: Computer-based, virtual-reality laparoscopic surgical simulators have
      several advantages over traditional video trainers. One of these advantages is
      that performance can be evaluated using unique computer-derived metrics, which
      can be digitally archived for analysis at a time convenient to instructors. This
      study sought to determine whether the computer-derived metrics for a unique
      hybrid simulator correlated with laparoscopic surgical skill. METHODS: For this
      study, 24 medical students (3rd year), 19 surgical residents (postgraduate years
      1-5), and 3 attending surgeons were invited to perform four different tasks three
      times in a hybrid laparoscopic trainer (ProMIS). Instruction with minimal
      supervision occurred at a time convenient to each subject. The four tasks in
      order of complexity were laparoscopic orientation, object positioning, sharp
      dissection, and intracorporeal knot tying. The metrics automatically recorded
      were time, path length, and smoothness. The laparoscopic operative experience for
      each user was quantified using case logs. RESULTS: A statistically significant
      correlation was observed between experience and performance for all three metrics
      for tasks 2 to 4 (p < 0.01). Smoothness was the only metric that correlated with
      the laparoscopic orientation task. Within tasks, time and smoothness correlated
      much more strongly with experience and to a similar degree. The strongest
      correlation was observed for the knot-tying task (r(2) = 0.60 for time and 0.59
      smoothness). CONCLUSIONS: The computer-derived metrics measured by the hybrid
      trainer correlate with laparoscopic experience. These metrics are automatically
      calculated and stored. This may make skills assessment and training a more time
      efficient endeavor for instructors and trainees alike. Further study is necessary
      to determine whether specific metrics are better indicators of actual skill.

PMID- 18347860
TI  - Routine ileal intubation during screening colonoscopy: a useful maneuver?
AB  - BACKGROUND: The utility of routine ileoscopy as a component of screening
      colonoscopy is unclear. Many endoscopists believe that routine intubation of the
      terminal ileum is a requirement for a full-screening colonoscopy. The authors
      have hypothesized that routine ileal intubation during screening colonoscopy is
      of little diagnostic value. METHODS: A retrospective analysis was performed using
      a prospectively maintained colonoscopy database of patients identified as
      undergoing a screening colonoscopy. All had undergone intubation of the terminal
      ileum at a tertiary referral center. Those who had undergone screening
      colonoscopy at the Mayo Clinic (Rochester, MN) were entered prospectively into a
      database. The study identified 6,408 patients who met the criteria of having
      terminal ileal intubation at the time of screening colonoscopy. The main outcome
      measured was abnormality of the terminal ileum at ileal intubation. RESULTS:
      Ileoscopy showed grossly abnormal findings for only 1% of the patients, and
      pathologic abnormalities were identified for only 0.3% of all the patients.
      CONCLUSIONS: The findings support the conclusion that intubation of the terminal
      ileum should not be a required part of screening colonoscopy.

PMID- 18347861
TI  - Cold nebulization used to prevent heat loss during laparoscopic surgery: an
      experimental study in pigs.
AB  - BACKGROUND: Prolonged abdominal laparoscopy is responsible for a significant drop
      in core body temperature. Various modifications of the conditioning for the
      insufflating carbon dioxide (CO(2)) to prevent the specific hypothermia related
      to the insufflated gas have been tested. This study aimed to investigate the
      effects on core temperature of insufflation with unheated humidified CO(2) using
      the Aeroneb system compared with the use of standard gas and gas made hot and wet
      using a warming and humidifying system (Pall system). METHODS: A prospective four
      session study was conducted to investigate a homogeneous group of four pigs.
      After inducation of general anesthesia, all the animals were treated successively
      with the following protocols in a randomized order at 8-day intervals: control
      (no pneumoperitoneum), standard (unheated, unhumidified CO(2)), Aeroneb
      (unheated, humidified CO(2) by cold nebulization), and Pall (heated, humidified
      CO(2)). The core temperature of the animals was recorded every 10 min. RESULTS:
      Analysis of variance (ANOVA) confirmed a difference between the insufflation
      conditions in the evolution of temperature over time (p = 0.004). The method of
      contrast showed the following results. After 30 min, the core temperature of the
      Aeroneb group fell significantly less than that of the standard group (p =
      0.036). After 100 min, the core temperature of the Pall group fell significantly
      less than that of the standard group (p = 0.024). After 80 min, the core
      temperature of the standard group fell significantly more than that of the
      control group (p = 0.035). In the Aeroneb group, the core temperature dropped
      less than in the Pall and control groups, but the difference did not reach
      statistical significance. CONCLUSIONS: Cold humidification of insufflating CO(2)
      prevents heat loss associated with pneumoperitoneal insufflation at least as
      efficaciously as warmed humidification of the gas.

PMID- 18347862
TI  - Redefining contraindications to laparoscopic colorectal resection for high-risk
      patients.
AB  - BACKGROUND: Patients with major comorbidities often are denied laparoscopic
      colorectal resections because they are thought to be at too "high risk."
      Paradoxically, these patients generally have the most to gain from a minimally
      invasive surgical approach. This study aimed to examine the feasibility and
      safety of laparoscopic colorectal resection to determine whether it is
      contraindicated for "high-risk" patients. METHODS: From August 1996 to February
      2004, 368 consecutive patients (95 men) undergoing a laparoscopic colorectal
      procedure by a single surgeon were prospectively studied with regard to pre-,
      peri-, and postoperative events. High-risk patients (n = 190) were defined as
      elderly (age, >80 years; n = 28), morbidly obese (body mass index [BMI], >30
      kg/m(2); n = 55), American Society of Anesthesiology (ASA) 3 or 4 (n = 130), and
      recipients of preoperative radiotherapy (n = 54). Multiple risk factors were
      found for 67 patients, 7 of whom had three risk factors. The median age of the
      patients was 66 years (range, 19-92 years). The diagnoses included rectal cancer
      (n = 48), diverticulitis (n = 43), colon cancer (n = 34), benign polyp (n = 26),
      and other (n = 39). The following procedures were performed: colon resection (n =
      114; left, 63; right, 41; total abdominal colectomy, 10), rectal resection (low
      anterior resection or pouch) (n = 49), coloanal anastomosis (n = 23), and other
      (n = 4). Data regarding intent to treat, operative events, morbidity, mortality,
      and outcomes were analyzed and form the basis of this report. RESULTS: No
      mortalities occurred. The major morbidity rate was 2%. There were no anastomotic
      leaks. The cases were laparoscopically performed (94%) or laparoscopically
      assisted, or were converted to open procedure (3%). The median estimated blood
      loss was 200 ml, and only 5% required perioperative transfusion. The
      perioperative course involved the following median periods: 2 days until flatus,
      3 days until bowel movement, 1 day until clear liquid diet, 3 days until a
      regular diet, and 5 days until hospital discharge. CONCLUSION: In experienced
      hands, laparoscopic colorectal resection can be performed safely for "high-risk"
      surgical patients. The better than expected outcomes in this patient population
      reinforce the benefits of minimally invasive surgery for this patient group and
      argues against using parameters of increased age, morbid obesity, high ASA class,
      or preoperative radiation alone as contraindications to even complex laparoscopic
      colorectal procedures.

PMID- 18347863
TI  - A single training center's experience with 200 consecutive cases of
      diverticulitis: can all patients be approached laparoscopically?
AB  - BACKGROUND: This study aimed to evaluate the outcomes for consecutive patients
      with diverticular disease who underwent elective laparoscopic sigmoid colectomy.
      METHODS: Data for this patient population were collected by chart review and
      analyzed retrospectively. RESULTS: Between December 2001 and March 2007, 200
      consecutive patients (93 men and 107 women) with an average age of 55 years were
      identified. All cases were managed by one of two colorectal surgeons. Of the 200
      patients, 158 had recurrent diverticulitis, 20 had fistulas, 12 had abscesses, 8
      had strictures, 1 had a mass, and 1 had a bleed. The mean operative time was 159
      min, and the conversion rate was 8%. A total of 30 early postoperative
      complications occurred for 26 patients including wound infection (n = 9), ileus
      (n = 8), Clostridium difficile colitis (n = 3), urinary retention (n = 3), pelvic
      abscess (n = 2), deep vein thrombosis and pulmonary embolism (n = 1), pneumonia
      (n = 1) urinary tract infection (n = 1), anastomotic leak (n = 1), and small
      bowel obstruction (n = 1). Late complications experienced by 11 patients included
      Clostridium difficile colitis (n = 3), incisional hernia (n = 3), wound infection
      (n = 3), wound hematoma (n = 1), and intraabdominal hemorrhage (n = 1).
      CONCLUSIONS: The authors believe it is feasible to offer elective laparoscopic
      sigmoid colectomy to all patients with symptomatic diverticular disease despite
      preoperative risk factors.

PMID- 18347864
TI  - Laparoscopic cortical-sparing adrenalectomy for bilateral pheochromocytoma.
AB  - A 32-year-old female with asthma was hospitalized for pneumonia in 2/06. She
      underwent a CT scan of the chest which revealed an incidental finding of
      bilateral adrenal masses. On further questioning, she admitted to palpitations
      and flushing. She was normotensive. Biochemical workup was significant for
      elevated urinary norepinephrine and normetanephrines, and plasma catecholamine
      level. MIBG scan showed positive uptake in the left adrenal gland consistent with
      pheochromocytoma. T2 weighted MRI showed bilateral adrenal masses, left greater
      than right. After adequate alpha blockade with phenoxybenzamine, the patient
      underwent a laparoscopic left adrenalectomy. Pathology revealed a 3.5 cm
      pheochromocytoma. The patient then underwent a right cortical-sparing
      adrenalectomy to avoid complete adrenal insufficiency and Addisonian crisis. The
      choice of operation was made realizing the potential for increased bleeding,
      which was further complicated by the patient's Jehovah's Witness beliefs, which
      prohibit transfusion of any blood products. At surgery, a small, well
      circumscribed mass of the inferior right adrenal gland was found, and excised in
      its entirety. A postoperative ACTH-stimulation test showed appropriate cortisol
      response. Pathology revealed a 1.5 cm pheochromocytoma, and the patient recovered
      uneventfully. Cortical-sparing adrenalectomy has been reported with success rates
      of 65-100% in avoiding exogenous steroid dependence.(1,2) Bilateral
      pheochromocytoma remains the most common indication. Risks for both recurrence
      and malignancy require lifelong follow-up in these patients.

PMID- 18347865
TI  - Transvaginal endoscopic appendectomy in humans: a unique approach to NOTES-
      world's first report.
AB  - BACKGROUND: Natural orifice translumenal endoscopic surgery (NOTES) is the newest
      technique emerging in the field of surgery. There are several techniques
      described in the literature; however there is no standardization yet. We describe
      the transvaginal approach for endoscopic appendectomy in humans, probably the
      world's first report. MATERIALS AND METHODS: Pneumoperitoneum was achieved via a
      Veress needle in the umbilicus. Routine 12-mm endoscope and routine instruments
      were used. Peritoneal access was gained via a transvaginal approach through the
      posterior fornix. RESULTS: Out of a total of six patients, a totally endoscopic
      transvaginal appendectomy was successfully performed for one patient. The other
      five patients were either converted to conventional laparoscopy or aided by a
      laparoscope. The average age of the patients was 29.5 years. The mean operating
      time was 103.5 min. Hospital stay was 1-2 days. The follow-ups were scheduled at
      7 days, 30 days, 90 days, and 6 months. The vaginal wound was examined by the
      gynecologist and found to have completely healed during the first and second
      follow-up. DISCUSSION: So far in humans, transgastric appendectomy and
      cholecystectomy, and transvaginal cholecystectomy have been reported. A
      transvaginal endoscopic appendectomy in humans has not been reported yet. The
      transvaginal approach provided a normal image of the target organ, unlike the
      inverted image of a transgastric approach caused by the inability to manipulate
      the scope outside the mouth. The technical ease of the procedure and early
      outcome seem satisfactory, although comparative studies are needed to confirm
      this.

PMID- 18347866
TI  - Laparoscopic treatment of metabolic syndrome in patients with type 2 diabetes
      mellitus.
AB  - BACKGROUND: Metabolic syndrome refers to risk factors for cardiovascular disease.
      Hyperglycemia is a critical component contributing to the predictive power of the
      syndrome. This study aimed to evaluate the results from the laparoscopic
      interposition of an ileum segment into the proximal jejunum for the treatment of
      metabolic syndrome in patients with type 2 diabetes mellitus and a body mass
      index (BMI) lower than 35. METHODS: Laparoscopic procedures were performed for 60
      patients (24 women and 36 men) with a mean age of 51.7 +/- 6.4 years (range, 27
      66 years) and a mean BMI of 30.1 +/- 2.7 (range, 23.6-34.4). All the patients had
      a diagnosis of type 2 diabetes mellitus (T2DM) given at least 3 years previously
      and evidence of stable treatment using oral hypoglycemic agents, insulin, or both
      for at least 12 months. The mean duration of type 2 diabetes mellitus was 9.6 +/-
      4.6 years (range, 3-22 years). Metabolic syndrome was diagnosed for all 60
      patients. Arterial hypertension was diagnosed for 70% of the patients (mean
      number of drugs, 1.6) and hypertriglyceridemia for 70%. High-density lipoprotein
      was altered in 51.7% of the patients and the abdominal circumference in 68.3%.
      Two techniques were performed: ileal interposition (II) into the proximal jejunum
      and sleeve gastrectomy (II-SG) or ileal interposition associated with a diverted
      sleeve gastrectomy (II-DSG). RESULTS: The II-SG procedure was performed for 32
      patients and the II-DSG procedure for 28 patients. The mean postoperative follow
      up period was 7.4 months (range, 3-19 months). The mean BMI was 23.8 +/- 4.1
      kg/m(2), and 52 patients (86.7%) achieved adequate glycemic control.
      Hypertriglyceridemia was normalized for 81.7% of the patients. An high-density
      lipoprotein level higher than 40 for the men and higher than 50 for the women was
      achieved by 90.3% of the patients. The abdominal circumference reached was less
      than 102 cm for the men and 88 cm for the women. Arterial hypertension was
      controlled in 90.5% of the patients. For the control of metabolic syndrome, II
      DSG was the more effective procedure. CONCLUSIONS: Laparoscopic II-SG and II-DSG
      seem to be promising procedures for the control of the metabolic syndrome and
      type 2 diabetes mellitus. A longer follow-up period is needed.

PMID- 18347867
TI  - Evaluation of real-time infrared intraoperative cholangiography in a porcine
      model.
AB  - BACKGROUND: Intraoperative cholangiograms (IOCs) may increase cost, surgical
      time, and radiation exposure of staff and patients. The authors introduce the
      application of passive infrared imaging to intraoperative cholangiography as a
      feasible alternative to traditional fluoroscopic IOCs. METHODS: A porcine model
      was used in which the gallbladder, cystic duct, common bile duct (CBD), and
      duodenum were exposed and an 18-gauge angiocatheter was inserted into the cystic
      duct. Infrared emission was detected using a digital infrared camera positioned
      30 to 60 cm above the abdomen. Infrared images were taken in real time
      (approximately 1/s) during infusion of room-temperature saline. A thermoplastic
      polymer stone then was inserted into the CBD. Once the artificial stone was
      placed, room-temperature saline was again injected. A standard single-shot
      renograffin IOC was obtained to confirm the obstruction. The experiment was
      concluded by creation of a lateral 2-mm CBD injury immediately proximal to the
      duodenum followed by infusion of room-temperature saline. RESULTS: Six pigs were
      used in this study. Baseline infrared imaging was able to capture a visible
      temperature decrease, outlining the lumen of the CBD. With injection of room
      temperature saline, a decrease in temperature was visualized as a dark area
      representing flow from the CBD to the duodenum. After placement of the synthetic
      stone, real-time infrared images displayed slowing of the injected bolus by the
      obstruction. The obstruction was correlated with fluoroscopic IOCs. Finally,
      after partial transection of the CBD, the infrared camera visualized saline
      flowing from the site of injury out into the peritoneal cavity. CONCLUSIONS: The
      CBD anatomy, obstruction, and injury can be clearly visualized with an infrared
      camera. Intraoperative infrared imaging is an emerging method already being used
      in several surgical fields. Ultimately, the integration of infrared and
      laparoscopic technology will be necessary to make infrared technology important
      in laparoscopic cholecystectomy.

PMID- 18347868
TI  - Outcome of endoscopic balloon dilation of strictures after laparoscopic gastric
      bypass.
AB  - OBJECTIVE: Stricture formation at the gastrojejunal anastomosis is a relatively
      common complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). The
      objective of this study was to report the incidence of stomal strictures after
      LRYGB in our institution and report our experience with their management by
      endoscopic balloon dilatation. METHODS: This is a retrospective study of 1012
      patients who underwent LRYGB from January 2001 to May 2004. Patients with nausea
      and vomiting after the surgery, suspected of having gastrojejunal (GJ)
      anastomotic stricture, had upper endoscopy. Stomas less than 10 mm in diameter,
      or those not allowing passage of the scope were considered significant strictures
      and were treated with balloon dilations. Dilations were performed with a through
      the-scope (TTS) balloon, with sizes ranging from 6 to 18 mm. The following data
      were collected from these patients: age, sex, body mass index (BMI),
      comorbidities, size of balloon catheter, time from surgery until symptoms onset,
      number of endoscopies needed to relief symptoms, and complications of the
      procedure. RESULTS: Sixty-one patients (46 females and 15 males) were found to
      have anastomotic strictures, corresponding to an incidence of 6%. In total, 134
      upper endoscopies were performed, with 128 dilatations. The average age was 41.7
      years (range: 19-68 years); mean preoperative BMI was 45 kg/m(2) (range: 42-61
      kg/m(2)). Mean time from surgery to symptoms onset was 2 months (range: 1-6
      months). The number of dilations per patient was as follows: a single dilation in
      28% of patients, two dilations in 33%, three dilations in 26%, four dilations in
      11.5%, and five dilations in 1.5% of patients. All the patients responded to
      dilation without need for formal surgical revision. However, after balloon
      dilatation three patients (4.9%), all females, had bowel perforation by
      radiological criteria (free air on X-ray), which corresponded to 2.2% of all
      dilatations. The maximum balloon size used in this group was 13.5 mm. All three
      patients had exploratory laparoscopy without finding of perforation site. They
      were treated with bowel rest, intravenous antibiotics for 7 days, and drain
      placement. No factors were identified to predict a risk of perforation.
      CONCLUSION: This is the largest study to evaluate the outcome of endoscopic
      dilatations of GJ strictures after RYGB. Endoscopic balloon dilation is a safe
      and effective treatment for anastomotic strictures. However, it carries a small
      risk of perforation. Further case studies are needed to determine risk factors
      for perforation and if the patients can be managed conservatively in this
      setting.

PMID- 18347869
TI  - Presentation and management of Morgagni hernias in adults: a review of 298 cases.
AB  - BACKGROUND: Morgagni hernias are a very rare form of diaphragmatic hernias. No
      robust studies have been performed to show the true natural history of this
      disease process. This study aimed to summarize clinically relevant data with
      respect to Morgagni hernias in adults. These data should help surgeons workup,
      diagnose, and treat Morgagni hernias in adult patients. METHODS: A literature
      search was performed using PubMed, Google scholar, and the following key words:
      Morgagni, Larrey, retrosternal, retrocostoxiphal, retrochondrosternal,
      parasternal, substernal, anterior diaphragmatic, and subcostosternal. All case
      reports and series after 1951 that pertained to adults were included in the
      review. The following data points were queried: age, sex, presentation, studies
      used during workup, laterality, surgical approach, hernia sac management,
      specific laparoscopic techniques, and follow-up evaluation. RESULTS: These
      criteria were met by 135 articles representing 298 patients. Based on the data
      provided, several conclusions regarding this disease process can be drawn. Most
      patients (72%) present with symptoms related to their hernia. Pulmonary
      complaints are the most common symptoms (36%). Men present earlier in life than
      women. Thoracotomy is the most widely used surgical approach (49%). However,
      laparoscopic repair has gained popularity since its first report in 1992.
      Laparoscopic surgeons usually repair the defect with mesh (64%) and do not remove
      the hernia sac (69%). Laparoscopic repair can be performed with a low
      complication rate (5%) and a short hospital stay (3 days). Outcomes of other
      surgical approaches also are reported. CONCLUSIONS: Using modern surgical
      techniques including laparoscopy, repair of Morgagni hernia can be performed
      safely with a short hospital stay and with little morbidity or mortality.

PMID- 18347870
TI  - Identification of softness syndrome-associated candidate genes and DNA sequence
      variation in the sea squirt, Halocynthia roretzi.
AB  - The mortality of sea squirts, Halocynthia roretzi, with softness syndrome
      threatens the sea squirt aquaculture industry in Asian countries. The molecular
      approach to understanding the pathogenesis of softness syndrome began with
      differential gene expression analysis of tissues from normal and dying organisms.
      In the present study, we show that the expression of Halocynthia roretzi
      metalloproteinase (HrMMP) was significantly upregulated in the tissues of dying
      organisms through screening of differentially expressed genes, reverse
      transcription-polymerase chain reaction (RT-PCR), and real-time PCR. HrMMP is
      composed of 482 amino acids, contains a conserved domain found in the astacin
      family, and has typical metalloproteinase activity. To discriminate between the
      differential expression of the HrMMP gene in normal and dying organisms, we
      cloned the HrMMP gene promoter and identified a polymorphism in the HrMMP
      promoter region that resulted in distinct polymorphisms (G/T) at position - 308
      bp. These results suggest that organisms with the GT genotype may have more
      resistance to softness syndrome than those with the TT genotype. These findings
      suggest that the HrMMP promoter polymorphism may be associated with an increased
      risk of softness syndrome in cultivated sea squirts and should be evaluated as a
      candidate molecular marker for the selective breeding of softness syndrome
      resistant sea squirts.

PMID- 18347871
TI  - Molecular characterization and expression pattern of two pheromone-binding
      proteins from Spodoptera litura (Fabricius).
AB  - Pheromone perception is thought to be mediated by pheromone-binding proteins
      (PBPs) in the lymph surrounding the olfactory receptors. We cloned and
      characterized two PBP genes (SlitPBP1 and SlitPBP2) from the common cutworm,
      Spodoptera litura (F.; Lepidoptera: Noctuidae), which encode PBPs belonging to
      two different PBP groups. Western blot analysis of the crude antennal extracts
      with SexigPBP1 antibody revealed a single immunoreactive band (much stronger in
      male than in female) of approximately 16 kDa, in agreement with the calculated
      values for SlitPBPs. From genomic DNA, two introns and a similar exon/intron
      structural pattern were identified in each PBP genes, but the introns differed in
      length within and between PBP genes. The expression patterns of two SlitPBP
      genes, with respect to tissue distribution and sex, were further investigated by
      reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time PCR.
      Although the two PBP genes were expressed only in the antennae of both sexes,
      reflecting the antennal specificity of PBPs, the transcription levels of PBP
      genes differed between the sexes and the genes. The transcription levels of
      SlitPBP1 and SlitPBP2 in females were only 2.1% and 7.0%, respectively, relative
      to those in males, and the levels of PBP2 compared with PBP1 were 31.4% and 95.3%
      in males and females, respectively. These differential expression levels might
      suggest different roles played by the two SlitPBPs in the perception of sex
      pheromone both in males and females.

PMID- 18347873
TI  - Esophageal cancers with synchronous or antecedent head and neck cancers: a more
      formidable challenge?
AB  - BACKGROUND: The presence of synchronous or antecedent head and neck cancers may
      complicate management of patients with primary esophageal cancer. METHODS: From
      January 1982 to December 2004, by means of a prospectively collected database, we
      compared information from 119 patients with esophageal cancers who had
      synchronous or antecedent head and neck cancers with information from 1555
      patients who only had squamous cell esophageal cancer in a tertiary referral
      academic hospital. RESULTS: There were far more men and younger patients in those
      who had head and neck cancers, and multicentric tumors were also more common.
      Hypopharyngeal tumors were the most frequently encountered head and neck cancer
      and were found in 36.1% of patients. Resection rates of the primary esophageal
      cancers were similar in those who had head and neck cancers and in those who only
      had esophageal cancer (60.7% vs. 61.7% P = .74). Overall postoperative
      complication rates were not different. Thirty-day mortality rates were 0% and
      2.9% for those who did and did not have head and neck tumors, respectively (P =
      .25). The respective hospital mortality rates were 10.3% and 9.5% (P = .83).
      Median survival for resectable esophageal cancers was 9.2 months for the former
      group and 13.4 months for the latter (P = .02). CONCLUSIONS: Esophagectomy rates
      did not differ when synchronous or antecedent head and neck cancers were present.
      Similar postoperative morbidity and mortality rates could be achieved. The
      presence of additional head and neck tumors imparted a worse long-term prognosis.

PMID- 18347874
TI  - Dendritic cell enumeration.

PMID- 18347875
TI  - Knowledge helps, but alone it is not enough.

PMID- 18347876
TI  - Benefits, limitations, and harm of local excision for rectal cancer.

PMID- 18347877
TI  - A model for mechano-electrical feedback effects on atrial flutter interval
      variability.
AB  - Atrial flutter is a supraventricular arrhythmia, based on a reentrant mechanism
      mainly confined to the right atrium. Although atrial flutter is considered a
      regular rhythm, the atrial flutter interval (i.e., the time interval between
      consecutive atrial activation times) presents a spontaneous beat-to-beat
      variability, which has been suggested to be related to ventricular contraction
      and respiration by mechano-electrical feedback. This paper introduces a model to
      predict atrial activity during atrial flutter, based on the assumption that
      atrial flutter variability is related to the phase of the reentrant activity in
      the ventricular and respiratory cycles. Thus, atrial intervals are given as a
      superimposition of phase-dependent ventricular and respiratory modulations. The
      model includes a simplified atrioventricular (AV) branch with constant
      refractoriness and conduction times, which allows the prediction of ventricular
      activations in a closed-loop with atrial activations. Model predictions are
      quantitatively compared with real activation series recorded in 12 patients with
      atrial flutter. The model predicts the time course of both atrial and ventricular
      time series with a high beat-to-beat agreement, reproducing 96+/-8% and 86+/-21%
      of atrial and ventricular variability, respectively. The model also predicts the
      existence of phase-locking of atrial flutter intervals during periodic
      ventricular pacing and such results are observed in patients. These results
      constitute evidence in favor of mechano-electrical feedback as a major source of
      cycle length variability during atrial flutter.

PMID- 18347878
TI  - The STARD statement for reporting diagnostic accuracy studies: application to the
      history and physical examination.
AB  - OBJECTIVE: The Standards for Reporting of Diagnostic Accuracy (STARD) statement
      provided guidelines for investigators conducting diagnostic accuracy studies. We
      reviewed each item in the statement for its applicability to clinical examination
      diagnostic accuracy research, viewing each discrete aspect of the history and
      physical examination as a diagnostic test. SETTING: Nonsystematic review of the
      STARD statement. INTERVENTIONS: Two former STARD Group participants and 1 editor
      of a journal series on clinical examination research reviewed each STARD item.
      Suggested interpretations and comments were shared to develop consensus.
      MEASUREMENTS AND MAIN RESULTS: The STARD Statement applies generally well to
      clinical examination diagnostic accuracy studies. Three items are the most
      important for clinical examination diagnostic accuracy studies, and investigators
      should pay particular attention to their requirements: describe carefully the
      patient recruitment process, describe participant sampling and address if
      patients were from a consecutive series, and describe whether the clinicians were
      masked to the reference standard tests and whether the interpretation of the
      reference standard test was masked to the clinical examination components or
      overall clinical impression. The consideration of these and the other STARD items
      in clinical examination diagnostic research studies would improve the quality of
      investigations and strengthen conclusions reached by practicing clinicians.
      CONCLUSIONS: The STARD statement provides a very useful framework for diagnostic
      accuracy studies. The group correctly anticipated that there would be nuances
      applicable to studies of the clinical examination. We offer guidance that should
      enhance their usefulness to investigators embarking on original studies of a
      patient's history and physical examination.

PMID- 18347879
TI  - Cachexia worsens prognosis in patients with resectable pancreatic cancer.
AB  - INTRODUCTION: Pancreatic cancer is the fourth leading cause of cancer-related
      death in Western countries with a poor prognosis (5-year survival rates, 25% in
      patients after tumor resection with adjuvant treatment; overall, the 5-year
      survival rate is about 4%; Jemal et al., CA Cancer J Clin, 55:10-30, 2005). Many
      patients develop a cachectic status during the progression of the disease, and
      this syndrome accounts for up to 80% of deaths in patients with advanced
      pancreatic cancer. Remarkably, there are only a few data available on the impact
      of cachexia in patients with pancreatic cancer scheduled for tumor resection.
      MATERIAL AND METHODS: Therefore, in this study, 227 consecutive patients with
      ductal adenocarcinoma of the pancreas were documented over an 18-month period
      regarding the prevalence of cachexia and its influence on perioperative morbidity
      and mortality with a special interest to postoperative weight gain and survival
      in a prospectively designed database and followed up. RESULTS: In 40.5% of the
      patients, cachexia was already present at the time of operation. The cachectic
      patients did present in a worse nutritional status, represented by lower protein,
      albumins, and hemoglobin levels. Despite no significant differences in tumor
      size, lymph node status, and CA19-9 levels, the resection rate in patients with
      cachexia was reduced (77.8% vs. 48.9%) due to a higher rate of metastatic disease
      in patients with cachexia. The morbidity and in-hospital mortality revealed no
      significant difference. However, patients with and without cachexia lost weight
      after operation, and the weight gain started not until 6 months after operation.
      The survival in patients with cachexia was significantly reduced in patients
      undergoing tumor resection as well as in palliative treated patients. CONCLUSION:
      Cachexia has a significant impact on survival and performance status in
      palliative patients as well as in patients operated for pancreatic cancer. But
      tumor-related cachexia is not necessarily dependent on tumor size or load and
      that metastatic dedifferentiation of the tumor might be a critical step in the
      development of tumor-associated cachexia.

PMID- 18347880
TI  - A successful model of setting up a bariatric practice.
AB  - Vital for any surgeon choosing to perform bariatric surgery is to be financially
      savvy. Establishing a practice is not a simple matter. This article will describe
      how physicians can establish their practice in weight loss medicine. To better
      insure success, wisdom dictates that one perform a geographical study with
      respect to (1) obesity in the population, (2) number of bariatric surgeons in the
      area, (3) the nature of the insurance companies, (4) the type of insurance
      (health maintenance organization, HMO versus private pay versus Medicare,
      Medicaid, etc.), and (5) the leverage that the practice might be able to acquire
      (what is not being done by your competitors). To improve the financial strength
      of your practice, (1) learn what must be improved within your practice; (2)
      increase the ratio of time in the operating room to time in the office; (3)
      increase the number of patients referred to you. Most important is flexibility;
      the only people who really survive are chameleons because only chameleons adapt
      to different situations. Setting up a bariatric practice can be quite difficult,
      especially in the academic setting, but it is not impossible. A team approach is
      essential, whether one is speaking of a team of characteristics that make an
      office suitable, a team of experts within the office to appropriately evaluate
      patients, a team of professionals in the office to ensure efficient insurance
      approval, or a team of persons in the operating room to ensure that the surgery
      is optimized. The local environment must always be kept in mind.

PMID- 18347881
TI  - An unusual suspect: coconut bezoar after laparoscopic Roux-en-Y gastric bypass.
AB  - Nausea and vomiting after gastric bypass are common, but some of the underlying
      causes may be life threatening or, in some cases, unusual. This case report
      describes a patient who underwent laparoscopic Roux-en-Y gastric bypass and whose
      postoperative course was complicated by a bezoar in the gastric pouch. To our
      knowledge, this is the first published report addressing a coconut bezoar in the
      gastric pouch after gastric bypass surgery. Coconut (cocos nucifera) is known to
      form emulsions and suspensions, properties likely to have contributed to this
      patient's condition. Nutritional counseling should be an ongoing process in the
      postoperative care of gastric bypass patients in an effort to prevent serious
      complications that may arise from dietary indiscretions.

PMID- 18347882
TI  - Preoperative upper gastrointestinal testing can help predicting long-term outcome
      after gastric banding for morbid obesity.
AB  - BACKGROUND: Gastric banding (GB) is one of the most popular bariatric procedures
      for morbid obesity. Apart from causing weight loss by alimentary restriction, it
      can interfere with functions of the esophagus and upper stomach. The aim of this
      study was to evaluate if the results of extensive preoperative upper GI testing
      were correlated with long-term outcome and complications after GB. METHODS: Using
      a prospectively maintained computerized database including all the patients
      undergoing bariatric operations in both our hospitals, we performed a
      retrospective analysis of the patients who underwent complete upper
      gastrointestinal (GI) testing (endoscopy, pH monitoring, and manometry) before
      GB. RESULTS: One hundred thirty-four patients underwent complete testing before
      GB. Abnormal pH monitoring (increased total reflux time, increased diurnal reflux
      time, increased number of reflux episodes) predicted the development of
      complications and especially pouch dilatation and food intolerance. The mean De
      Meester score was higher among patients who developed complications than in the
      remaining ones (25.4 vs 17.7, P=0.03). High lower esophageal sphincter pressure
      also predicted progressive long-term food intolerance. Endoscopic findings were
      not predictive of the long-term outcome. CONCLUSIONS: There is some association
      between the function of the upper digestive tract and long-term complications
      after gastric banding. Abnormal pH monitoring predicts overall long-term
      complications, especially food intolerance with or without reflux, and pouch
      dilatation, and a high lower esophageal sphincter pressure predicts long-term
      food intolerance. Extended upper gastrointestinal testing with endoscopy, 24-h pH
      monitoring, and esophageal manometry is probably worthwhile in selecting patients
      for gastric banding.

PMID- 18347883
TI  - Experience with the duodenal switch operation in the presence of intestinal
      malrotation.
AB  - The presence of intestinal malrotation (IM) may pose unexpected problems during
      bariatric operations. We reviewed the records of patients with IM undergoing
      bariatric operations at our institution over the last 5 years. Three patients
      underwent four procedures. These included an open duodenal switch, an attempted
      laparoscopic gastric bypass with open duodenal switch as a second-stage
      procedure, and lastly a laparoscopic robot-assisted duodenal switch. All patients
      have had good outcomes. The key anatomic principles of a tension-free duodeno
      enterostomy and maintaining appropriate orientation at the distal
      enteroenterostomy are emphasized.

PMID- 18347884
TI  - Laparoscopic totally stapled entero-enterostomy: a safe and reproducible new
      technique.
AB  - BACKGROUND: Laparoscopic gastric bypass for morbid obesity is a technically
      demanding procedure partially because of the necessity to construct two
      anastomoses. In this study, a new technique to perform the entero-enterostomy is
      presented. METHODS: We evaluated the procedure in a consecutive series of 100
      patients who underwent laparoscopic gastric bypass. Intra- and postoperative
      complications were analyzed. RESULTS: No complications in relation to the
      construction of the entero-enterostomy occurred. No leakage, kinking, or stenosis
      was observed during a mean follow-up of 13.5 months (range 6-20 months).
      CONCLUSION: This new technique for a totally stapled entero-enterostomy can be
      recommended.

PMID- 18347885
TI  - High association of posterior malleolus fractures with spiral distal tibial
      fractures.
AB  - Associations between fracture patterns are important and can ensure proper
      diagnosis and guide treatment. Occult posterior malleolus fractures associated
      with distal spiral tibia fractures often are underrecognized and the morbidity of
      a missed posterior malleolus injury can be substantial. We determined the
      association between the two injuries and evaluated the ability of a new protocol
      to improve management of these associated fractures. Of 62 consecutive patients
      with fractures of the distal third of the tibia, we retrospectively evaluated the
      first 39 patients and prospectively used a diagnostic protocol including computed
      tomography of the ankle in the subsequent 23 patients. The minimum followup was 3
      months (mean, 25 months; range, 3-68 months). Twenty-four patients (39%) had
      fractures of the posterior malleolus. Before initiation of the protocol,
      intraarticular fractures were recognized in 33% (with one delayed diagnosis and
      one missed diagnosis), and after institution of the protocol, the detection rate
      was 48% with no known missed injuries and complete followup; however, with the
      limited power the detection rates were similar without and with the protocol. A
      spiral distal tibial shaft fracture with a proximal fibula fracture should alert
      the surgeon to investigate an occult ankle injury, particularly of the posterior
      malleolus. A protocol including computed tomography of the ankle may detect more
      injuries in a larger study. LEVEL OF EVIDENCE: Level II, prognostic study.

PMID- 18347886
TI  - Anatomy of the greater trochanteric 'bald spot': a potential portal for abductor
      sparing femoral nailing?
AB  - Soft tissue injury occurs when using a piriformis portal for femoral nailing.
      Standard trochanteric portals also can injure the gluteus medius and external
      rotator tendons, which may be a source of hip pain after nailing. On the lateral
      facet of the greater trochanter, a "bald spot" may exist that is devoid of tendon
      insertion. This may be a potential portal for intramedullary nail insertion. We
      defined the dimensions and location of this region. Cadaveric specimens were
      dissected to expose the tendon insertions on the greater trochanter. A computer
      navigation system was used with a stylus and bone morphing to determine the
      tendon insertions and bald spot anatomy. The greater trochanteric bald spot is
      covered by the subgluteus medius bursa and has no tendon insertions. Its center
      lies 11 mm distal to the tip of the greater trochanter and 5 mm anterior to the
      midline. The shape is ellipsoid with a diameter of 21 mm. This region is large
      enough to accommodate the size of most nailing system reamers without tendon
      footprint infringement. Use of this modified entry site may reduce soft tissue
      injury with nailing procedures and minimize subsequent hip pain.

PMID- 18347887
TI  - Treatment of primary isolated shoulder sepsis in the adult patient.
AB  - Isolated shoulder sepsis is an uncommon clinical problem with little information
      in the literature on causative organisms and potential sequelae. We examined the
      organisms involved, surgical treatments, antibiotic treatments rendered, and
      complications in these cases. We retrospectively reviewed the records of 19 adult
      patients (19 shoulders) who underwent operative treatment of isolated shoulder
      sepsis from 1996 to 2005. Patient age, gender, laboratory studies, previous
      treatment, surgical procedures, surgical findings, cultured organism, antibiotic
      treatment, and complications were reviewed. The organisms included methicillin
      susceptible Staphylococcus aureus (five), Streptococcus B beta hemolytic (five),
      Staphylococcus epidermidis (three), negative cultures (two), Streptococcus
      viridans (one), Escherichia coli (one), methicillin-resistant S. aureus (one),
      and Propionibacterium acnes (one). We treated patients with intravenous
      antibiotics an average of 4.2 weeks (range, 3-8 weeks). One patient underwent
      humeral head resection with an antibiotic spacer. Another patient died during
      hospitalization. Open or arthroscopic debridement in conjunction with appropriate
      antibiotics appears effective in eradicating infection in most adults who present
      with shoulder sepsis. Functional outcome is poor in those patients with
      irreparable rotator cuff tears and/or cartilage loss. LEVEL OF EVIDENCE: Level
      IV, therapeutic study. See the Guidelines for Authors for a complete description
      of levels of evidence.

PMID- 18347888
TI  - Multidrug-resistant organisms in military wounds from Iraq and Afghanistan.
AB  - Mortality from battlefield wounds has historically declined, thanks to better
      surgical management, faster transport of casualties, and improved antibiotics.
      Today, one of the major challenges facing U.S. military caregivers is the
      presence of multidrug-resistant organisms in orthopaedic extremity wounds. The
      most frequently identified resistant strains of bacteria are Staphylococcus
      aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter
      calcoaceticus-baumannii complex. Overuse of broad-spectrum antibiotics may be an
      important factor in building resistant strains. Acinetobacter infections appear
      to hospital-acquired and not from an initial colonization of the injury. More
      research is required to give military physicians the tools they require to reduce
      the infection rate and defeat multidrug-resistant organisms.

PMID- 18347889
TI  - Staphylococcus aureus nasal decolonization in joint replacement surgery reduces
      infection.
AB  - Surgical site infections (SSIs) with Staphylococcus aureus are a recognized
      adverse event of hip and knee replacements. We evaluated the impact of a program
      to detect S. aureus nasal carriers before surgery with preoperative
      decolonization (using mupirocin twice daily for 5 days prior to surgery) of
      carriers. Nasal swab samples were obtained from patients prior to surgery from
      8/1/2003 through 2/28/2005. Samples were tested using real-time PCR technology to
      detect S. aureus. The group that developed S. aureus SSI was compared to a
      combined concurrent and historical control for one year following the operation.
      S. aureus caused 71% of SSIs in the combined control groups. Of the 1495 surgical
      candidates evaluated, 912 (61.0%) were screened for S. aureus; 223 of those
      screened (24.5%) were positive and then decolonized with mupirocin. Among the 223
      positive and decolonized patients, three (1.3%) developed a SSI. Among the 689
      screen-negative patients, four (0.6%) developed SSIs for an overall rate of
      0.77%. Among the 583 control patients who were not screened or decolonized, 10
      (1.7%) developed S. aureus SSIs. SSIs from other organisms were 0.44% and 0.69%,
      respectively. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines
      for Authors for a complete description of levels of evidence.

PMID- 18347890
TI  - Ligament reconstruction versus distal realignment for patellar dislocation.
AB  - Recently, medial patellofemoral ligament reconstruction has been emphasized for
      the treatment of patellar dislocation. This study compared the results of medial
      patellofemoral ligament reconstruction by adductor magnus tenodesis with distal
      patellar realignment in patients with recurrent patellar dislocation.
      Additionally, the development of patellofemoral osteoarthrosis was compared for
      these two procedures at a median 10-year followup. Between 1994 and 2000, 47
      consecutive patients were treated for recurrent patellar dislocation by adductor
      magnus tenodesis (18 knees) or Roux-Goldthwait procedure (29 knees).
      Redislocations, subjective symptoms, and functional outcomes were evaluated.
      Magnetic resonance imaging was performed at followup. The incidence of patellar
      redislocation after surgery was 7% in the adductor magnus group and 14% in the
      Roux-Goldthwait group. Median Kujala scores were 88 for the adductor magnus group
      and 86 for the Roux-Goldthwait group. Magnetic resonance imaging revealed
      patellofemoral articular cartilage lesions in 22 knees (73.3%) at followup,
      including 14 (46.6%) with full-thickness cartilage loss. Radiographs revealed
      patellofemoral osteoarthritis in five patients in the Roux-Goldthwait group and
      in none of the patients in the adductor magnus group. Adductor magnus tenodesis
      is a reliable method to treat recurrent patellar dislocation. The medial
      patellofemoral ligament reconstruction seems to reduce the risk of osteoarthrosis
      compared with distal realignment surgery. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 18347891
TI  - Vascular management in rotationplasty.
AB  - The Van Nes rotationplasty is a useful limb-preserving procedure for skeletally
      immature patients with distal femoral or proximal tibial malignancy. The vascular
      supply to the lower limb either must be maintained and rotated or transected and
      reanastomosed. We asked whether there would be any difference in the ankle
      brachial index or complication rate for the two methods of vascular management.
      Vessels were resected with the tumor in seven patients and preserved and rotated
      in nine patients. One amputation occurred in the group in which the vessels were
      preserved. Four patients died secondary to metastatic disease diagnosed
      preoperatively. The most recent ankle brachial indices were 0.96 and 0.82 for the
      posterior tibial and dorsalis pedis arteries, respectively, in the reconstructed
      group. The ankle brachial indices were 0.98 and 0.96 for the posterior tibial and
      dorsalis pedis arteries, respectively, in the rotated group. Outcomes appear
      similar using both methods of vascular management and one should not hesitate to
      perform an en bloc resection when there is a question of vascular involvement.

PMID- 18347892
TI  - Do patient expectations of spinal surgery relate to functional outcome?
AB  - It is important for surgeons to understand patients' expectations for surgery. We
      asked whether patient factors and preoperative functional outcome scores reflect
      the degree of expectations patients have for posterior spinal surgery. Second, we
      asked whether patients' expectations for surgery predict improvements in
      functional outcome scores after surgery. We prospectively enrolled 155
      consecutive surgical patients with greater than 90% followup. Patients'
      expectations were evaluated preoperatively along with SF-36 and Oswestry
      disability questionnaires. Postoperatively (6 months for decompression; 1 year
      for fusions), we quantified patient-derived satisfaction regarding whether
      expectations were met and by patient-derived functional outcome scores. In
      patients undergoing decompression, gender, SF-36 general health domain, and SF-36
      physical component score predicted patients with high expectations for surgery.
      Patients with high expectations also reported greater postoperative improvements
      in SF-36 role physical domain scores after surgery. Expectations for surgery were
      met in 81% of patients. In a subset of patients (21 of 143), expectations were
      not met. These patients reported lower mean preoperative SF-36 general health,
      vitality, and mean mental component scores.

PMID- 18347893
TI  - Behavioral frequency moderates the effects of message framing on HPV vaccine
      acceptability.
AB  - BACKGROUND: Research suggests that gain-framed messages are generally more
      effective than loss-framed messages at promoting preventive health behaviors.
      Virtually all previous studies, however, have examined prevention behaviors that
      require regular and repeated action to be effective. Little is known about the
      utility of message framing for promoting low-frequency prevention behaviors such
      as vaccination. Moreover, few studies have identified mediators of framing
      effects. PURPOSE: We investigated whether behavioral frequency (operationalized
      as the number of shots required) moderated the effect of framed health messages
      on women's intentions to receive the human papillomavirus (HPV) vaccine. We also
      sought to identify mediators of framing effects. METHOD: Undergraduate women (N =
      237) were randomly assigned to read an HPV vaccination booklet that varied by
      message frame (gain vs. loss) and behavioral frequency (one shot vs. six shots).
      RESULTS: We observed a frame-by-frequency interaction such that the loss-framed
      message led to greater vaccination intentions than did the gain-framed message
      but only among participants in the one-shot condition. Perceived susceptibility
      to HPV infection mediated the observed framing effects. CONCLUSIONS: This study
      provides an important exception to the commonly observed gain-framed advantage
      for preventive health behaviors. Loss-framed appeals appear to be particularly
      effective in promoting interest in low-frequency prevention behaviors such as HPV
      vaccination.

PMID- 18347894
TI  - Associations of perceived community environmental attributes with walking in a
      population-based sample of adults with type 2 diabetes.
AB  - BACKGROUND: No studies have yet examined the associations of physical
      environmental attributes specifically with walking in adults with type 2
      diabetes. PURPOSE: The purpose of this study was to examine associations of
      perceived community physical environmental attributes with walking for transport
      and for recreation among adults living with type 2 diabetes. METHODS:
      Participants were 771 adults with type 2 diabetes who completed a self
      administered survey on perceived community physical environmental attributes and
      walking behaviors. RESULTS: Based on a criterion of a minimum of 120-min/week,
      some 29% were sufficiently active through walking for transport and 33% through
      walking for recreation. Significantly higher proportions of those actively
      walking for transport and for recreation had shops or places to buy things close
      by (67.8% and 60.9%); lived within a 15-min walk to a transit stop (70.6% and
      71.0%); did not have dead-end streets close by (77.7% and 79.8%); reported
      interesting things to look at (84.8% and 84.4%); and lived close to low-cost
      recreation facilities (81.3% and 78.8%). In addition, those actively walking for
      transport reported living in a community with intersections close to each other
      (75.6%) and with sidewalks on their streets (88.1%). When these variables were
      entered simultaneously into logistic regression models, living close by to shops
      was positively related to walking for transport (OR = 1.92, 99% CI = 1.11-3.32).
      CONCLUSIONS: Consistent with findings from studies of healthy adult populations,
      positive perceptions of community environmental attributes are associated with
      walking for transport among adults with type 2 diabetes. The now-strong public
      health case for environmental innovations to promote more walking for transport
      is further reinforced by the potential to benefit those living with diabetes.

PMID- 18347895
TI  - Analyzing theoretical mechanisms of physical activity behavior change in breast
      cancer survivors: results from the activity promotion (ACTION) trial.
AB  - BACKGROUND: We previously reported that a physical activity (PA) behavior change
      intervention based on the theory of planned behavior (TPB) increased PA and
      quality of life in breast cancer survivors. PURPOSE: To examine the effects of
      our interventions on TPB variables and to determine if PA at 12 weeks follow-up
      was mediated by TPB variables at 4 weeks. METHODS: Breast cancer survivors (N =
      377) were randomly assigned to receive either a standard public health
      recommendation for PA (SR group), a step pedometer alone, or one of two TPB-based
      behavior change interventions consisting of print materials (alone or combined
      with a step pedometer). For the purpose of this study, we compared the two TPB
      based intervention groups (INT group) to the SR group. RESULTS: Compared to the
      SR group, the INT group reported more favorable changes in instrumental attitude
      (mean difference = 0.13; 95% CI = -0.01 to 0.23; d = 0.19; p = 0.077), intention
      (mean difference = 0.33; 95% CI = 0.10 to 0.56; d = 0.33; p = 0.006), and
      planning (mean difference = 0.39; 95% CI = 0.04 to 0.73; d = 0.26; p = 0.027).
      Mediation analyses indicated that both planning and intention partially mediated
      the effects of the intervention on PA at 12 weeks. CONCLUSIONS: Our TPB-based
      behavior change intervention resulted in small improvements in the TPB constructs
      that partially mediated the effects of our intervention on PA behavior.
      Additional research with the TPB is warranted.

PMID- 18347896
TI  - Is there something unique about marriage? The relative impact of marital status,
      relationship quality, and network social support on ambulatory blood pressure and
      mental health.
AB  - BACKGROUND: Having close social relationships and being married specifically have
      been reliably associated with health benefits including lower morbidity and
      mortality. PURPOSE: The purpose of this study was to examine the influence of
      marital status, relationship quality, and network support on measures of
      psychological and cardiovascular health. METHOD: We examined ambulatory blood
      pressure (ABP) among 204 married and 99 single males and females (N = 303).
      RESULTS: We found that both marital status and marital quality were important.
      Married individuals had greater satisfaction with life (SWL) and blood pressure
      dipping than single individuals. High marital quality was associated with lower
      ABP, lower stress, less depression, and higher SWL. Importantly, contrasting
      those who are unmarried with those in low-quality marriages, we find that single
      individuals had lower ABP-suggesting that single individuals fare better than
      their unhappily married counterparts. Likewise, having a supportive network did
      not moderate (i.e., buffer) the effects of being single or unhappily married.
      CONCLUSIONS: Findings indicate being married per se is not universally
      beneficial, rather, the satisfaction and support associated with such a
      relationship is important. However, marriage may be distinctive, as evidence
      further suggests that support from one's network does not compensate for the
      effect of being single. These results highlight the complexities in understanding
      the influence of social relationships on long-term health, and they may help
      clarify the physiological pathways by which such associations exist.

PMID- 18347897
TI  - Stress and quality of life in breast cancer recurrence: moderation or mediation
      of coping?
AB  - BACKGROUND/PURPOSE: Diagnosis with breast cancer recurrence often brings high
      levels of stress. Successful coping to alleviate stress could improve patients'
      quality of life (QoL). The intervening role coping plays between stress and QoL
      may depend on the types of stress encountered and the types of coping strategies
      used. The present study investigates the longitudinal relationships between
      stress, coping, and mental health QoL. METHODS: Breast cancer patients recently
      diagnosed with recurrence (N = 65) were assessed shortly after the diagnosis and
      4 months later. Four moderation and four mediation models were tested using
      hierarchical multiple regressions and path analyses. In the models, either
      traumatic stress or symptom-related stress at recurrence diagnosis was a
      predictor of mental health QoL at follow-up. Both engagement and disengagement
      coping strategies were tested as moderators or mediators between stress and QoL.
      RESULTS: Engagement coping moderated the effect of symptom stress on mental
      health QoL, whereas disengagement coping mediated the effects of both traumatic
      stress and symptom stress on mental health QoL. CONCLUSION: The findings imply
      that interventions teaching engagement coping strategies would be important for
      patients experiencing high symptom stress, while discouraging the use of
      disengagement coping strategies would be important for all patients.

PMID- 18347898
TI  - Behavioral medicine: celebrating the past, inspiring the future. Abstracts of the
      29th Annual Meeting and Scientific Sessions of the Society of Behavioral
      Medicine. March 26-29, 2008. San Diego, California, USA.

PMID- 18347899
TI  - The Annals is moving forward!

PMID- 18347900
TI  - The importance of context in understanding behavior and promoting health.
AB  - Behavior, the roles of behavior in health, health promotion, health, quality of
      life, and death are all context-dependent. This paper begins with a review of
      behavioral and ecological models, emphasizing their shared emphasis on context.
      It then turns to genetics and the importance of contexts in understanding genetic
      influences. Jumping from genes to geography, it examines how spatial analysis
      provides both a model and framework for considering contextual influence.
      Continuing with analytic models, it returns to genetics, and considers how it
      provide models for integrating our understanding of broad social and community
      influences. The paper extends this thinking through multilevel analysis and
      proposes "analytic multilevel designs" as a way of studying "context focused
      interventions" (as opposed to context independent interventions for which
      conventional experimental designs are often well-suited). It closes with
      reflections on ways in which we cultivate and extend our knowledge base and on
      the intellectual contexts of positivism and postmodernism that surround
      behavioral and ecological thinking.

PMID- 18347901
TI  - What types of evidence are most needed to advance behavioral medicine?
AB  - BACKGROUND: This editorial presents a perspective on the types of evidence most
      needed to advance behavioral medicine given the current status of the field.
      PURPOSE: The paper argues that the types of evidence most needed at present are
      evidence that is contextual, practical, and robust. METHODS: Each of the above
      issues is discussed with attention to characteristics of interventions;
      representativeness at the multiple levels of setting, clinical staff, and
      participants; and research design and measures. Arguments are made from
      philosophy of science, status of the literature, and future directions
      perspectives. RESULTS: The current dominant paradigm of reductionistic studies
      focused predominantly on internal validity using highly homogenous patients and
      academic settings is not and will not produce the desired translation to real
      world practice and policy. Instead, broader "practical" clinical and behavioral
      trials are needed that address the influence of the context in which programs are
      conducted, that include outcomes important to decision makers and communities,
      and that focus on moderating, mediating, and economic issues. CONCLUSIONS: To
      create programs that will be disseminable, a greater focus is needed on external
      validity and transparency of reporting. We need to realize that the world is
      complex and embrace and study this complexity to produce further progress. Such
      an approach can produce evidence that is both rigorous and relevant.

PMID- 18347902
TI  - Cognitive-behavioral stress management interventions for persons living with HIV:
      a review and critique of the literature.
AB  - BACKGROUND: Psychological adjustment and coping are central to human
      immunodeficiency virus (HIV) management. To improve HIV-infected patients'
      ability to cope with stress, a variety of stress management interventions have
      been designed and evaluated. PURPOSE: This paper provides a review and critique
      of the stress management literature, including a: (1) synthesis of core
      components of interventions for HIV-infected people, (2) summary of stress,
      coping, psychological, and health outcomes, and (3) methodological critique and
      guidance for future research. METHODS: We reviewed 21 stress management
      interventions designed for HIV-infected individuals that included both cognitive
      and behavioral skills training. RESULTS: Most studies noted positive changes in
      perceived stress, depression, anxiety, global psychological functioning, social
      support, and quality of life. However, results were mixed for coping and health
      status outcomes, and a majority of studies employed only brief follow-up periods,
      focused on HIV-infected MSM, and did not address HIV-specific stressors.
      CONCLUSIONS: Stress management interventions for HIV-infected persons are a
      promising approach to facilitate positive adjustment. However, this literature is
      limited by measurement problems, research design features, a narrow focus on HIV
      infected men who have sex with men, and feasibility concerns for intervention
      dissemination. Future stress management interventions should address these
      limitations and the unique psychosocial needs of HIV-infected patients using
      briefer, more cost-effective formats.

PMID- 18347903
TI  - Methamphetamine and poly-substance use among gym-attending men who have sex with
      men in New York City.
AB  - BACKGROUND: Methamphetamine and other drug use has been documented among men who
      have sex with men (MSM). Patterns of use may be influenced by point of
      recruitment into these studies. PURPOSE: The aim of this study is to describe
      patterns of methamphetamine and other drug use and to delineate psychosocial and
      demographic factors which accompany these patterns of use in a sample of MSM
      attending gyms in New York City. METHODS: Active recruitment strategies were
      implemented to ascertain a sample of 311 MSM. Participants completed a one-time
      survey regarding both health risks and health promotion. RESULTS: Methamphetamine
      use in the last 6 months was reported by 23.8% of men. Inhalation and smoking
      were the most common modes of administration, and 84% of men reported more than
      one mode of use. Study participants also indicated a variety of other substances
      used, including but not limited to alcohol, inhalant nitrates, and 3,4
      methylenedioxymethamphetamine (MDMA). Compared to nonusers, methamphetamine users
      were more likely to report being black or Latino, depressed, HIV-positive,
      perceiving more benefits of unprotected sex, and understanding masculinity in
      sexual terms. CONCLUSIONS: These data suggest that health-risk behaviors are
      common among MSM who are regularly using a gym and are indicative of the
      complexities of health issues for this segment of the population.

PMID- 18347904
TI  - Mediation of adult fruit and vegetable consumption in the National 5 A Day for
      Better Health community studies.
AB  - BACKGROUND: The 5 A Day for Better Health community studies demonstrated in
      randomized trials the efficacy of population-based strategies to increase fruit
      and vegetable consumption in diverse geographic areas and settings. PURPOSE:
      Mediation analysis can help to elucidate the theoretical basis of changing
      dietary habits. This is important for informing more powerful cancer prevention
      and control interventions to achieve broad public health impact. METHODS: Five
      sites that focused on adults were included in mediation analyses to determine
      whether theoretically derived constructs assessed at baseline and follow-up
      contributed to explaining change in fruit and vegetable (F&V) consumption. These
      variables were knowledge, self-efficacy, and autonomy/responsibility. Stage of
      change also was considered as a potential moderating variable. RESULTS: Self
      efficacy and knowledge of the 5 A Day recommendation increased in those who
      received the interventions and were positively associated with higher F&V.
      Mediation of intervention effect was demonstrated for these variables.
      Autonomy/responsibility did not meet the criteria for mediation. There was no
      evidence of differential effect of mediators according to baseline stage.
      CONCLUSIONS: The present study findings provide strong support for mediation of
      F&V consumption by two variables: self-efficacy and knowledge. The authors
      discuss the findings in relation to study limitations and future research
      directions.

PMID- 18347905
TI  - Benefit finding in response to BRCA1/2 testing.
AB  - BACKGROUND: Undergoing genetic testing for BRCA1/2 mutations may be accompanied
      by elevated worry and distress, but the potential for the experience to catalyze
      positive psychological and life changes has not been studied. PURPOSE: This study
      was designed to examine the relationship between mutation carrier status,
      personal cancer history, and the potential positive impact of genetic testing
      (i.e., benefit finding). We also tested two predictors of benefit finding (BF)
      derived from the theoretical and empirical literature on positive outcomes of
      stress: impact of the experience and approach-oriented coping. METHODS: Women
      undergoing genetic testing for BRCA1/2 mutations (n = 108) completed
      questionnaires assessing test-related distress, approach-oriented coping, and BF
      after receipt of test results. BRCA1/2 status was determined from genetic test
      results and personal cancer history from interviews conducted with study
      participants before testing. RESULTS: Reports of BF in this sample were highly
      variable, as some women did not perceive the testing experience as having any
      noticeable effect on their lives, whereas others reported positive changes
      similar to those observed in cancer patients (e.g., significantly improved
      relationships, greater appreciation for life). Contrary to hypotheses, women who
      tested positive for BRCA1/2 did not report higher levels of BF in response to
      genetic testing than those who tested negative. However, BF scores were elevated
      among mutation carriers who had a previous cancer diagnosis. As predicted, test
      related distress and approach-oriented coping were also positively associated
      with BF, and approach-oriented coping mediated the relationship between carrier
      status x cancer history and BF. CONCLUSIONS: Findings suggest that positive life
      changes can occur among women who test positive for BRCA1/2 mutations,
      particularly cancer survivors.

PMID- 18347906
TI  - Social support and self-care of patients with heart failure.
AB  - BACKGROUND: Social support can influence treatment adherence of patients with
      chronic illnesses, which may explain the positive effects of social support on
      heart failure (HF) outcomes. PURPOSE: To investigate the effects of social
      support among patients with HF, we examined whether aspects of social support
      were associated with self-care, including medication adherence, dietary
      adherence, and HF symptom monitoring functions. METHODS: We recruited 74 patients
      with HF from cardiology clinics of a Veterans Affairs Medical Center and a
      university-affiliated hospital, and tested the relationships between social
      support and the patients' self-care. RESULTS: Consistent with previous research
      in older adults, family members, especially spouses, were often involved in the
      medical care of patients with chronic HF and provided a range of levels of
      support to patients. Self-care was generally poor, as measured across several
      self-care domains. Perceived social support was moderately associated with
      relatively better self-reported medication and dietary adherence, and other
      aspects of self-care such as daily weighing. CONCLUSIONS: These findings suggest
      that a relatively higher level of self-care is an important correlate of social
      support and may explain how social support influences HF outcomes. This study
      also suggests that family members should play a greater part in clinical care
      focused on improving self-care.

PMID- 18347907
TI  - Preferences for a patient-centered role orientation: association with patient
      information-seeking behavior and clinical markers of health.
AB  - BACKGROUND: Few data exist examining how patients' preferred role orientation
      (patient-centered or provider-centered) is associated with "patient-centered"
      behavior and clinical markers of health. PURPOSE: The purpose of the study is to
      investigate how patients' preferred role orientation is associated with
      information-seeking behavior and clinical markers of health in a chronically ill
      population. METHODS: Participants were 189 hypertensive patients, at two VA
      Medical Centers and four community-based clinics, who completed measures of
      preferred role orientation and medication information seeking. Lab values of
      patients' blood pressure, LDL cholesterol, and glycosylated hemoglobin A1c were
      used as clinical markers. RESULTS: Preference for a patient-centered role was
      associated with seeking medication information from various sources (e.g., the
      internet [OR = 1.14, 95% CI = 1.05-1.23]) and with the number of sources from
      which patients obtained information (beta = .21, p = 0.005). However, patient
      centered preferences were also associated with higher systolic blood pressure
      (beta = 0.16, p = 0.04), higher diastolic blood pressure (beta = .15, p = 0.04),
      and higher LDL cholesterol (beta = 0.17, p = 0.04). There was no association with
      glycosylated hemoglobin A1c (beta = -0.10, p = 0.36). CONCLUSIONS: Patients who
      preferred a patient-centered role engaged in behavior consistent with their
      preferences, but had higher blood pressure and less favorable lipid levels. These
      findings are discussed in terms of the nature and treatment of certain chronic
      conditions that may explain why a patient-centered role orientation is associated
      with a less favorable clinical profile in some contexts.

PMID- 18347908
TI  - Perceived stress is associated with impaired T-cell response to HPV16 in women
      with cervical dysplasia.
AB  - BACKGROUND: Infection with high-risk subtypes of human papillomavirus (HPV) is a
      central factor in the development of cervical neoplasia. Cell-mediated immunity
      against HPV16 plays an important role in the resolution of HPV infection and in
      controlling cervical disease progression. Research suggests that stress is
      associated with cervical disease progression, but few studies have examined the
      biological mechanisms that may be driving this association. PURPOSE: This study
      examines whether stress is associated with immune response to HPV16 among women
      with cervical dysplasia. METHODS: Seventy-four women presenting for colposcopy
      completed measures of health behaviors, stressful life events and perceived
      stress. A blood sample was obtained to evaluate proliferative T-cell response to
      HPV16, and a cervical sample was obtained during gynecologic exam for HPV-typing.
      RESULTS: More than 55% tested positive for one or more HPV subtypes. Women who
      did not show proliferative responses to HPV (i.e. non-responders) were more
      likely to be HPV(+) compared to women who had a response (i.e. responders).
      Consistent with study hypotheses, logistic regression revealed that higher levels
      of perceived stress were associated with a non-response to HPV16, controlling for
      relevant covariates. Stressful life events were not associated with T-cell
      response to HPV. CONCLUSIONS: Higher levels of perceived stress are associated
      with impaired HPV-specific immune response in women with cervical dysplasia,
      suggesting a potential mechanism by which stress may influence cervical disease
      progression.

PMID- 18347909
TI  - Hyperventilation symptoms are linked to a lower perceived health in asthma
      patients.
AB  - BACKGROUND: Hyperventilation symptoms are among the sensations asthma patients
      tend to report during exacerbations of their disease. However, little is known
      about their importance for the patients' perceived well-being. METHOD: We
      therefore studied the association of reported hyperventilation symptoms (Asthma
      Symptom Checklist) with perceived physical and mental health (36-item Short-form
      Health Survey) in a sample of primary care asthma patients (N = 190). We also
      studied the potential role of perceived control of asthma (Perceived Control of
      Asthma Questionnaire) in mediating any association between these variables.
      RESULTS: In hierarchical multiple regression analyses controlling for
      demographics, asthma severity, and other asthma symptoms (obstruction,
      congestion, panic-fear, irritation, and fatigue), hyperventilation symptoms were
      significantly associated with both physical and mental health status. This
      association was partially mediated by perceived control of asthma. CONCLUSION: It
      is possible that hypocapnia creates symptoms that asthma patients cannot control
      by using their antiasthmatic medication, thus compromising their perceived
      control over the management of their asthma, and consequently their perceived
      health. Behavioral interventions should address the problem of hyperventilation
      in asthma.

PMID- 18347910
TI  - The effects of race-related stress on cortisol reactivity in the laboratory:
      implications of the Duke lacrosse scandal.
AB  - BACKGROUND: The experience of race-related stressors is associated with
      physiological stress responses. However, much is unknown still about the complex
      relationship between how race-related stressors are perceived and experienced and
      potential moderators such as strength of racial identity. PURPOSE: This research
      examines the impact of a real-life stressor and strength of race identity on
      physiological responses to a social evaluative threat induced in the laboratory.
      METHODS: Salivary cortisol measures were collected throughout a stressor
      protocol. African-American participants were also randomized to one of two
      conditions designed to promote either racial identification or student
      identification, before the experimental task. Unexpectedly, a highly publicized
      real-life racial stressor, the Duke Lacrosse (LaX) scandal, occurred during the
      course of the data collection. This allowed for pre-post LaX comparisons to be
      made on cortisol levels. RESULTS: These comparisons showed that across both
      priming conditions, participants post-LaX had highly elevated cortisol levels
      that were nonresponsive to the experimental stress task, while their pre-LaX
      counterparts had lower cortisol levels that exhibited a normal stress response
      pattern. Furthermore, this effect of LaX was significantly moderated by gender,
      with women having lower mean cortisol levels pre-LaX but significantly greater
      cortisol levels than all other groups post-LaX. CONCLUSIONS: These results
      suggest that recent exposure to race-related stress can have a sustained impact
      on physiological stress responses for African Americans.

PMID- 18347911
TI  - Physical activity, self-efficacy, and quality of life in multiple sclerosis.
AB  - BACKGROUND: Quality of life (QOL) is compromised among individuals with multiple
      sclerosis (MS). Self-efficacy and physical activity have been positively
      associated with QOL in persons with MS, and based on a social cognitive
      perspective, the relationship between physical activity and QOL might be indirect
      and accounted for by self-efficacy. PURPOSE: We tested the hypothesis that
      physical activity would be indirectly associated with QOL through a pathway that
      included self-efficacy. METHODS: Participants were 133 individuals with a
      definite diagnosis of MS who completed the Godin Leisure-Time Exercise
      Questionnaire, Multiple Sclerosis Self-Efficacy scale, and Multiple Sclerosis
      Impact Scale. RESULTS: Path analysis indicated that those with MS who were more
      physically active had greater self-efficacy for function and control, and self
      efficacy for function and control were associated with greater physical and
      psychological components of QOL. CONCLUSIONS: Our findings support physical
      activity as a possible modifiable behavior for mitigating reductions of QOL by
      improving self-efficacy in individuals with MS.

PMID- 18347912
TI  - Barriers to supervised exercise training in a randomized controlled trial of
      breast cancer patients receiving chemotherapy.
AB  - BACKGROUND: Exercise adherence is a challenge for breast cancer patients
      receiving chemotherapy but few studies have identified the key barriers. PURPOSE:
      In this paper, we report the barriers to supervised exercise in breast cancer
      patients participating in a randomized controlled trial. METHODS: Breast cancer
      patients initiating adjuvant chemotherapy (N = 242) were randomly assigned to
      usual care (n = 82) or supervised resistance (n = 82) or aerobic (n = 78)
      exercise. Participants randomized to the two exercise groups (n = 160) were asked
      to provide a reason for each missed exercise session. RESULTS: The two exercise
      groups attended 70.2% (5,495/7,829) of their supervised exercise sessions and
      provided a reason for missing 89.5% (2,090/2,334) of their unattended sessions.
      The 2,090 reasons represented 36 different barriers. Feeling sick (12%), fatigue
      (11%), loss of interest (9%), vacation (7%), and nausea/vomiting (5%) accounted
      for the most missed exercise sessions. Disease/treatment-related barriers (19 of
      the 36 barriers) accounted for 53% (1,102/2,090) of all missed exercise sessions.
      Demographic and medical variables did not predict the types of exercise barriers
      reported. CONCLUSIONS: Barriers to supervised exercise in breast cancer patients
      receiving chemotherapy are varied but over half can be directly attributed to the
      disease and its treatments. Behavioral support programs need to focus on
      strategies to maintain exercise in the face of difficult treatment side effects.

PMID- 18347913
TI  - Exploring physical activity preferences.

PMID- 18347914
TI  - The diversity of KIR gene in Chinese Northern Han population and the impact of
      donor KIR and patient HLA genotypes on outcome following HLA-identical sibling
      allogeneic hematopoietic stem cell transplantation for hematological malignancy
      in Chinese people.
AB  - Killer cell immunoglobulin-like receptors (KIRs) are members of a group of
      molecules that specifically recognize HLA class I ligands and are found on
      subsets of human lymphopoetic cells. The number of KIR loci can vary between
      individuals, resulting in a heterogeneous array of possible KIR genes. The range
      of observed profiles has been explained by the occurrence of two haplotype
      families termed A and B, which can be distinguished on the basis of certain KIR
      sequences. Immunogenetic analysis of different ethnic populations shows
      significant differences in terms of the distribution for group A and group B
      haplotypes. Recently, attention has been focused on the role of killer cell
      immunoglobulin-like receptor (KIR)-ligand incompatibility in the graft-versus
      host direction between donor and recipient in allogeneic hematopoietic stem-cell
      transplantation (ASCT). The goal of this study was to study the frequency of
      specific KIR genes in Chinese Northern Han population and evaluate the role of
      KIR-ligand mismatch in Chinese HLA-identical sibling hematopoietic stem cell
      transplantation patients with hematological malignancy. Here genomic DNA from 150
      Northern Chinese Han individuals was typed for the presence or absence of KIR
      genes. Seventy-four allogeneic stem cell transplantation donor/recipient pairs
      were typed for HLA-A, B, C and KIR. Sixteen KIR genes were observed in the
      population, and framework genes 3DL3, 3DP1, 2DL4, and 3DL2 were present in all
      individuals. Twenty-two different genotypes were found. Group A haplotypes
      outnumbered group B haplotypes in frequency by approximately 3:1, with
      individuals having two group A haplotypes accounting for 51.9% (78/150). We
      observed that 57 out of 74 (77.3%) donor-recipient pairs could be characterized
      by lack of recipient HLA ligand for donor KIR. We observed that 36 out of 45
      (80%) donor-recipient HLA-identical sibling transplant pairs could be
      characterized by lack of recipient HLA ligand for donor KIR. Cumulative incidence
      analysis of aGVHD in patients undergoing HLA-identical sibling hematopoietic stem
      cell transplantation in this study demonstrated a decreased incidence of severe
      aGVHD in patients lacking HLA ligand for donor-inhibitory KIR2DL1 (31.4 vs. 70%,
      P = 0.029). And also in AML (acute myeloid leukemia) patients lacking HLA ligand
      for donor-inhibitory KIR and KIR2DL1 (17.6 vs. 75%, P = 0.03). Our data
      demonstrated that the Chinese Han population is distinct in KIR gene frequencies
      and putative KIR haplotypes in comparison to some other populations. Almost all
      allogeneic donors could be characterized as having an inhibitory KIR for each of
      the three known class I ligands. KIR and KIR2DL1 mismatch is associated with
      lower aGVHD in Chinese after HLA-identical sibling hematopoietic stem cell
      transplantation.

PMID- 18347915
TI  - The Q-type C2H2 zinc finger subfamily of transcription factors in Triticum
      aestivum is predominantly expressed in roots and enriched with members containing
      an EAR repressor motif and responsive to drought stress.
AB  - Q-type C2H2 zinc finger proteins (ZFPs) form a subfamily of transcription factors
      that contain a plant-specific QALGGH amino acid motif. A total of 47 expressed Q
      type C2H2 zinc finger genes in bread wheat (Triticum aestivum) (designated TaZFP)
      were identified from the current databases. Protein sequence analysis for the
      presence of ERF-associated amphiphilic repressor (EAR) motif sequences from known
      transcriptional repressors revealed that 26% of the TaZFP subfamily members
      contain an EAR motif. Quantitative RT-PCR analysis of the mRNA distribution of 44
      TaZFP genes in various organs revealed that 30 genes were predominantly expressed
      in the roots. The majority of the TaZFP genes showed significant changes in their
      mRNA levels during leaf development and aging. Expression of 37 TaZFP genes in
      the leaves and roots responded to drought stress at least in one organ with 74%
      of the drought-responsive TaZFP genes being down-regulated in the drought
      stressed roots. In contrast, only 6 out of the 44 TaZFP genes showed expression
      changes in the leaves with sucrose treatment. Expression of 50% of the drought
      responsive TaZFP genes in the leaves (16 genes analysed) did not respond to ABA
      treatment, indicating that some TaZFP genes are involved in ABA-independent
      signalling pathways. These results indicate that the Q-type TaZFP subfamily is
      likely to have an important role in wheat roots and is enriched with members that
      are potentially involved in regulating cellular activities during changes of the
      physiological status of plant cells, as it occurs during drought stress or leaf
      development/aging.

PMID- 18347916
TI  - Erionite series minerals: mineralogical and carcinogenic properties.
AB  - Erionite is a human and animal carcinogen and one of the most toxic minerals
      known. Erionite deposits have been reported in many countries; however, it is
      only in the area of three villages of Cappadocia, Turkey, that environmental
      exposure to erionite has been demonstrated to be the cause of an epidemic of the
      disease mesothelioma. In the USA, no cases of mesothelioma have been reliably
      proven to be the result of erionite exposure, though the possibility exists.
      Erionite samples from three villages of the Cappadocia region were characterized
      mineralogically and compared with three different standards from the USA. Micro
      morphological details of erionite minerals using a high-resolution field-emission
      SEM showed that microstructures of "bundles", "fibers", and "fibrils" are
      important physical properties of fibrous erionite minerals. Typical lung burden
      of erionite and asbestos fibers were compared in terms of number of fibers.
      Assuming the lung burden of fibers in a human mesothelioma victim is about 1 mg,
      and the hazardous fibers are approximately 1 mum in diameter and 10 mum long,
      that milligram contains approximately 40 million asbestos and 50 million erionite
      fibers. These microstructures of erionite minerals draw attention to the concepts
      of surface area or surface-area-to-volume ratio and their relationship to the
      carcinogenicity of the mineral. The larger surface area creates a wider platform
      for mineral-cell interaction and thus more possibilities of proliferative
      transformation of mesothelial cells. Consequently, understanding the exact
      mineralogical properties will help determination of the true carcinogenic
      mechanism(s) of the mineral for prevention and possibly treatment of malignant
      mesothelioma.

PMID- 18347917
TI  - Characterization of different compost extracts using Fourier-transform infrared
      spectroscopy (FTIR) and thermal analysis.
AB  - Compost extract or "compost tea" is a liquid extract of compost obtained by
      mixing compost and water for a defined period of time. Compost tea contains
      nutrients and a range of different organisms and is applied to the soil or
      directly to plants with the principal aim of suppressing certain plant diseases.
      In addition, the application of compost tea supplies nutrients and organic matter
      to the soil. Thermal analysis and Fourier transform infrared spectroscopy (FTIR)
      are two widely applied analytical techniques for establishing the stability of
      compost, and although numerous studies have evaluated the capacity of compost tea
      to suppress plant diseases, there are no studies employing these techniques to
      characterize compost-tea. For the present study, 12 compost extracts were
      produced under varying conditions in a purpose-built reactor. Two different
      composts, an stable compost produced from manure and an unstable compost produced
      from municipal solid waste, respectively, two aeration systems (aerated and non
      aerated extracts) and three temperatures (10, 20 and 30 degrees C) were used in
      these experiments. The extracts were freeze-dried and subsequently analysed,
      together with the two composts, by means of FTIR and thermal analysis. Extracts
      produced from high stability compost, independently of the conditions of aeration
      and temperature, showed very similar results. In contrast, differences among
      extracts produced from the unstable compost were more noticeable. However, the
      different conditions of aeration and temperature during the production of the
      extracts only explained partially these differences, since the transformations
      undergone by compost over the 3 months that the experiments lasted were also
      reflected in the composition of the extracts. In spite of everything, extraction
      process favoured the degradation of easily oxidizable organic matter, which was
      more abundant in unstable compost. This degradation was more intense for non
      aerated processes, probably due to the longer duration of these (10 days) with
      respect to aerated extractions (2 days). The effect of temperature was not clear
      in these experiments, although high temperatures could increase micro organism
      activity and consequently favour the degradation of easily oxidizable organic
      matter.

PMID- 18347918
TI  - Ecological and morphological attributes of parthenogenetic Japanese Schwiebea
      species (Acari: Acaridae).
AB  - We examined life history traits and spermathecal morphology of both sexual and
      thelytokous Schwiebea mite species to determine ecological and morphological
      attributes during the evolution of parthenogenesis in this lineage. We
      reconstructed a molecular phylogeny of eight Japanese species using the internal
      transcribed spacer 1 (ITS1) of the ribosomal DNA (rDNA) and compared the sex
      ratio, developmental period, and egg number (fecundity) of each species within a
      species group by rearing them in the laboratory. Habitat preference was also
      analyzed from both collection and literature data. The reconstructed molecular
      phylogeny suggested that parthenogenesis evolved independently multiple times in
      this lineage. There were three clusters in the tree, in each of which the
      idiosoma, leg, setae, and spermathecal morphology of females was similar or
      identical; this suggested that mites in the same cluster were sister species.
      There was no relationship between sexual mode and life history traits or habitat
      preference. These results suggest that sexual and asexual species use different
      microhabitats. Because S. similis (sexual), S. elongata (thelytokous), and S.
      estradai (thelytokous) were in the same cluster and spermathecae of the first two
      were similar while that of the last was distinctively reduced, we hypothesized
      that speciation occurred in this order and that spermathecae are reduced and
      eventually lost during the course of parthenogenetic evolution.

PMID- 18347919
TI  - How do Neoseiulus californicus (Acari: Phytoseiidae) females penetrate densely
      webbed spider mite nests?
AB  - The persea mite Oligonychus perseae is a pest of avocado trees that builds
      extremely dense webbed nests that protect them against natural enemies, including
      phytoseiid mites. Nests have one or two marginal entrances that are small and
      flattened. The predatory mite Neoseiulus californicus co-occurs with O. perseae
      in the avocado orchards of the south-east of Spain. Penetration inside nests
      through the entrances by this predator is thought to be hindered by its size and
      its globular-shaped body. However, in the field it has repeatedly been found
      inside nests that were clearly ripped. Perhaps penetration of the nests has been
      facilitated by nest wall ripping caused by some other species or by unfavourable
      abiotic factors. However, to assess whether N. californicus is also able to enter
      the nest of O. perseae by itself, we carried out laboratory experiments and made
      a short film. They show how this predator manages to overcome the webbed wall,
      and that it can penetrate and forage inside nests of O. perseae.

PMID- 18347920
TI  - Genetic control of muscle development: learning from Drosophila.
AB  - Muscle development involves a complex sequence of time and spatially regulated
      cellular events leading to the formation of highly specialised syncytial muscle
      cells displaying a common feature, the capacity of contraction. Analyses of
      mechanisms controlling muscle development reveals that the main steps of muscle
      formation including myogenic determination, diversification of muscle precursors,
      myoblast fusion and terminal differentiation involve the actions of
      evolutionarily conserved genes. Thus dissecting the genetic control of muscle
      development in simple model organisms appears to be an attractive way to get
      insights into core genetic cascade that orchestrate myogenesis. In this respect,
      particularly insightful have been data generated using Drosophila as a model
      system. Notably, the interplay between intrinsic and extrinsic cues that
      determine the early myogenic decisions leading to the specification of muscle
      progenitors and those controlling myoblasts fusion are much better characterised
      in Drosophila than in vertebrate species. Also, adult Drosophila myogenesis,
      which leads to the formation of vertebrate-like multi-fibre muscles, emerges as a
      particularly well-adapted system to study normal and aberrant muscle development.

PMID- 18347921
TI  - Regulation of the smooth muscle contractile phenotype by nonmuscle myosin.
AB  - The contractile phenotype of a smooth muscle can broadly be classified as phasic
      or tonic. Following activation, phasic smooth muscle exhibits an initial period
      of rapid force activation, following which force falls to a lower steady state
      level. In contrast, force generated by tonic smooth muscle rises slowly to a
      sustained steady state. The differences in contractile patterns cannot be
      explained by the time course of either the Ca(2+) transient or phosphorylation of
      the 20-kDa regulatory myosin light chain (MLC(20)). Therefore, a molecular marker
      that defines tonic and phasic smooth muscle contractile properties remains
      elusive. Further, smooth muscle can maintain force at low levels of MLC(20)
      phosphorylation; often referred to as the latch state. The mechanism for the
      latch state is unknown and has been hypothesized to be due to a number of
      mechanisms including the formation of slowly cycling dephosphorylated or latch
      cross-bridges (Hai and Murphy, Am J Physiol 253:H1365-H1371, 1988). This review
      will focus evidence suggesting that nonmuscle myosin IIB (NMIIB) are the latch
      cross-bridges in smooth muscle and NMIIB content could define the tonic
      contractile phenotype.

PMID- 18347922
TI  - History of benign breast disease and risk of breast cancer among women in China:
      a case-control study.
AB  - BACKGROUND: Data from the Shanghai Breast Cancer Study were analyzed to evaluate
      the relationship between benign breast disease (BBD) and breast cancer among
      Chinese women with a self-report of physician-diagnosed BBD. METHODS: Study
      participants consisted of 3,452 breast cancer cases and 3,474 population controls
      recruited by the Shanghai Breast Cancer Study. In-person interviews were
      conducted to collect information on demographics and suspected risk factors for
      breast cancer, including a detailed history of BBD. Unconditional logistic
      regression was used to derive adjusted odds ratios (OR(adj)) and 95% confidence
      intervals (CI) for the association between self-reported BBD and breast cancer.
      RESULTS: Women with breast cancer were significantly more likely to have a self
      reported history of BBD including lobular proliferation (OR(adj) = 1.6; 95% CI
      1.4-1.8), fibroadenoma (OR(adj) = 1.9; 95% CI 1.6-2.3), and other BBD (OR(adj) =
      1.6; 95% CI 1.3-2.1). Breast cancer risk was lower for surgically treated
      fibroadenoma as compared to non-surgically treated and higher for other BBDs that
      were surgically treated versus non-surgically treated. CONCLUSIONS: Our results
      suggest that personal history of BBD is associated with an increased risk of
      future breast cancer among women in China. Surgical intervention for fibroadenoma
      may reduce the risk.

PMID- 18347923
TI  - Systematic review of prostate cancer's association with body size in childhood
      and young adulthood.
AB  - Body size relatively early in life may influence men's later rate of prostate
      cancer. We searched for published, English-language studies of the association
      between prostate cancer incidence or mortality and body size between ages 5 and
      29 years. We summarized analyses of childhood body size, early-adult waist
      circumference, and early-adult body mass index (BMI). Most study designs were
      case-control or retrospective cohort studies, in which body size was self
      reported and recalled. The few studies of childhood body size and early-adult
      waist circumference indicated null or weak associations. The results from studies
      of early-adult BMI were heterogeneous (p = 0.04) and showed evidence of funnel
      plot asymmetry. The random-effects rate ratio (RR) was 1.06 (95% confidence
      interval [CI]: 0.99, 1.14) per five-unit increase in BMI. Studies using measured
      (as opposed to self-recalled) height and weight (n = 3) tended to produce
      stronger associations: fixed-effects summary RR = 1.22 (1.06, 1.39). The same was
      true for studies that did not adjust for later-life BMI (n = 13): fixed-effects
      RR = 1.13 (1.06, 1.21). Examining only analyses of advanced or high-grade
      prostate cancers, results were heterogeneous (p < 0.01). The random-effects
      summary RR per five units of BMI was 1.01 (95% CI: 0.89, 1.15). In all the
      reviewed studies, the vast majority of men were of normal weight in childhood and
      early adulthood. Few studies presented data describing the association between
      prostate cancer and obesity (e.g., early-adult BMI > or = 30). The exact
      relationships between early-life body size and prostate cancer remain unclear but
      appear to be weak.

PMID- 18347924
TI  - Roadside Rhododendron pulchrum leaves as bioindicators of heavy metal pollution
      in traffic areas of Okayama, Japan.
AB  - The leaves of roadside Rhododendron pulchrum Sweet were examined as a
      bioindicator of traffic-related heavy metal pollution in Okayama. Total contents
      of heavy metals in roadside soil and the R. pulchrum leaves were determined.
      Results of correlation analyses showed significant correlations among Pb, Ni, and
      Zn contents of roadside soil and leaf samples. These results suggest that R.
      pulchrum is a useful bioindicator of heavy metal pollution in traffic areas. To
      identify traffic-related heavy metal pollution sources, traffic-related materials
      such as tires, asphalt pavement, and road paint were collected and analyzed. The
      results of analyses of our data show that Zn is emitted mainly from the abrasion
      of tires; Cr is emitted mainly from wear of the asphalt pavement. Furthermore,
      the respective lead isotope ratios in R. pulchrum leaves, soil, roadside dust,
      and traffic-related materials were measured using inductively coupled plasma mass
      spectrometry. The isotopic compositions of lead in R. pulchrum leaves were
      207Pb/206Pb = 0.861-0.871 and 208Pb/206Pb = 2.093-2.127, which agrees well with
      ratios in automobile wheel balance weights, suggesting that lead-containing
      products associated with automobiles, such as wheel balance weights, contribute
      to traffic-related lead pollution.

PMID- 18347925
TI  - Assessment of nitrate contamination due to groundwater pollution in north eastern
      part of Anantapur District, A.P. India.
AB  - The north eastern part of Anantapur district is in the state of Andhra Pradesh,
      India, is significant as it is covered by varied geological formations and has
      different land use and irrigation practices. Though ground water is the major
      drinking water source, deterioration in its quality is going unchecked. In such
      agro-economy based rural areas, the nitrate contamination is rampant and much
      attention has not been drawn towards this anthropogenic pollution. In the study
      area ground water samples from different hydrogeological set-up have been
      collected during the pre and post monsoon seasons and analysed for the major ions
      such as Ca, Mg, Na, K, CO(3), HCO(3), Cl, SO(4), NO(3) and F. The study revealed
      that 65% of the samples were found to be unsuitable for drinking purposes in the
      pre monsoon season and 45% in the post monsoon due to excess nitrate (>45 mg/l)
      content in the ground water. Among the different seasons and environs, nitrate
      was in highest concentration in the granitic terrain and canal command areas
      during pre monsoon season. The nitrate was found to decrease with depth in all
      the hydrogeological set-ups in both the seasons. Intense agriculture practices,
      improper sewerage and organic waste disposal methods were observed to contribute
      nitrate to the shallow and moderately deep aquifers.

PMID- 18347926
TI  - ACE gene polymorphism and cardiac structure in patients with insulin resistance.
AB  - AIMS: Angiotensin-converting enzyme (ACE) is a key enzyme in the production of
      angiotensin II, thus may participate in the modulation of cardiac growth. The aim
      of our study is to analyze the ACE gene I/D polymorphisms in patients with
      insulin resistance (IR) and to evaluate its relationship to left ventricular mass
      and functions. METHODS: Eighteen subjects (13 female and 5 male, mean age 39.8 +/
      14) with IR were enrolled in the present study. Twenty-three healthy people
      without IR were recruited as the control group. ACE amplification of DNA was
      performed by polymerase chain reaction methodology. Fasting glucose and insulin,
      postprandial glucose, homeostasis model assessment (HOMA-IR) and HOMA-beta, lipid
      profile, anthropometric measurements were assessed. Left ventricular structure
      and functions were measured by echocardiography. RESULTS: Distribution of I/D
      polymorphism of the ACE gene in the study group was as follows: genotype II-0%,
      ID-38.9%, DD-61.1% of patients. Distribution of individual genotypes was similar
      in patients with and without IR. No significant difference was found between
      genotype groups in terms of anthropometric measurements and metabolic parameters
      and blood pressure. Echocardiography showed no significant changes in left
      ventricular structure and functions in patients with IR. CONCLUSIONS: We
      considered that in patients with IR, there is no relationship between I/D
      polymorphism of the ACE gene and LVH.

PMID- 18347927
TI  - The development of the pediatric cardiac quality of life inventory: a quality of
      life measure for children and adolescents with heart disease.
AB  - OBJECTIVE: Mortality after surgery for congenital heart disease (CHD) has
      decreased. Quality of life (QOL) assessment in survivors has become increasingly
      important. The purpose of this project was to create the Pediatric Cardiac
      Quality of Life Inventory (PCQLI). METHODS: Items were generated through nominal
      groups of patients, parents, and providers. The pilot PCQLI was completed by
      children (age 8-12), adolescents (age 13-18), and their parents at three
      cardiology clinics. Item reduction was performed through analysis of items,
      principal components, internal consistency (IC), and patterns of correlation.
      RESULTS: A total of 655 patient-parent pairs completed the pilot PCQLI. Principal
      components identified included: impact of disease (ID); psychosocial impact (PI);
      and emotional environment (EE). After item reduction ID and PI had excellent IC
      (ID = 0.88-0.91; PI = 0.78-0.85) and correlated highly with each other (0.81
      0.90) and with the total score (TS) (ID = 0.95-0.96; PI = 0.87-0.93). EE was not
      correlated with ID, PI, or TS and was removed from the final forms. Two-ventricle
      CHD patients had a higher TS than single-ventricle CHD patients across all forms
      (P < 0.001). CONCLUSION: The PCQLI has patient and parent-proxy forms, has wide
      age range, and discriminates between CHD subgroups. The ID and PI subscales of
      the PCQLI have excellent IC and correlate well with each other and the TS.

PMID- 18347928
TI  - The Sun Health Research Institute Brain Donation Program: description and
      experience, 1987-2007.
AB  - The Brain Donation Program at Sun Health Research Institute has been in continual
      operation since 1987, with over 1000 brains banked. The population studied
      primarily resides in the retirement communities of northwest metropolitan
      Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit
      community-owned and operated health care provider. Subjects are enrolled
      prospectively to allow standardized clinical assessments during life. Funding
      comes primarily from competitive grants. The Program has made short postmortem
      brain retrieval a priority, with a 2.75-h median postmortem interval for the
      entire collection. This maximizes the utility of the resource for molecular
      studies; frozen tissue from approximately 82% of all cases is suitable for RNA
      studies. Studies performed in-house have shown that, even with very short
      postmortem intervals, increasing delays in brain retrieval adversely affect RNA
      integrity and that cerebrospinal fluid pH increases with postmortem interval but
      does not predict tissue viability.

PMID- 18347929
TI  - EGFR inhibitor enhances cisplatin sensitivity of oral squamous cell carcinoma
      cell lines.
AB  - Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer
      cell biology. EGFR has already been identified as an important target for cancer
      therapy, with various kinds of EGFR inhibitors currently used in treatment of
      several human cancers. Recently, EGFR and its downstream signaling pathways were
      identified as being associated with cisplatin sensitivity. In addition, EGFR
      inhibitors have shown significant promise for patients who failed cisplatin-based
      therapy. In this study, we investigated whether treatment with an EGFR inhibitor
      improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines.
      The effects of a combination of AG1478, a specific EGFR tyrosine kinase
      inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and
      cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in
      the two cisplatin-resistant cell lines compared with the corresponding parental
      cell lines. In addition, augmented inhibition of OSCC cell growth by the
      combination of AG1478 with cisplatin was found in both cell lines. These results
      suggest that the combination of an EGFR inhibitor and cisplatin may be useful as
      a rational strategy for the treatment of patients with oral cancer with acquired
      cisplatin resistance.

PMID- 18347930
TI  - Comparison of photon with electron boost in treatment of early stage breast
      cancer.
AB  - In the treatment of early stage breast cancer breast conserving surgery (BCS)
      followed by whole breast irradiation (WBI) is a standard method. The impact of
      the tumor bed boost following WBI is well-defined, but there are various delivery
      methods. In this study the electron and the photon boost techniques were
      compared. For 78 early stage breast cancer patients both CT based 3D conformal
      photon boost and electron boost plans were created. For dosimetric comparison
      coverage index (CI), external volume index (EI) and conformality index (COIN)
      were studied. Lung volume receiving a dose of 2 Gy was also reviewed. Seventy
      eight patients with 156 plans were compared. The mean tumor bed volume was
      measured as 61.39 cm3 the mean tumor bed-skin distance was 3.13 cm. In the case
      of CI and COIN significant differences were found in favor of the photon boost.
      In the comparison of EI no significant difference was detected between the two
      techniques. The mean lung volume receiving 2 Gy were 42.3 and 168.35 cm3, for
      photons and electrons respectively. In the adjuvant treatment of early stage
      breast cancer WBI followed by conformal photon boost showed to be superior to
      electron boost in focus of the COIN and CI.

PMID- 18347931
TI  - Early diagnosis of chemotherapy-induced cardiomyopathy: a prospective tissue
      Doppler imaging study.
AB  - The aim of our study was to compare the applicability of the conventional
      echocardiography and a novel method, tissue Doppler imaging (TDI) in detection of
      late or subclinical cardiotoxicity following anthracycline chemotherapy in long
      term follow up. Forty women (31 to 65 years) were enrolled, who had not received
      anthracyclines previously and had normal cardiac function. The control group
      consisted of 20 healthy persons of similar age range. In addition to standard
      echocardiographic measurements, each patient underwent specific measurements (E
      septum separation, pulmonary venous flow) as well. Furthermore, the myocardial
      velocity of numerous segments of the mitral anulus obtained with pulsed wave TDI
      was also detected over a two-year-long period. Systolic left ventricular function
      did not change significantly either in the study or in the control group. After
      one year, diastolic left ventricular function was impaired in 39 patients
      (97.5%), and 29 (72.5%) of these showed clear changes by means of the traditional
      E/A ratio and TDI. However, in ten patients (25%) the diastolic dysfunction could
      only be detected with TDI. At the end of the study diastolic dysfunction was
      detected in each patient, but in 13 patients (32.5%) the relaxation disorder
      could be revealed only with TDI. Detectable myocardial damage occurred in the
      study group as a result of anthracycline therapy. Our results confirmed our
      assumptions that TDI is a more precise and useful examination method than the
      traditional ones (E/A ratio or deceleration time) to demonstrate isolated
      diastolic dysfunction. TDI may become a regularly and more widely used
      noninvasive method to detect subclinical cardiotoxicity emerging after
      chemotherapy.

PMID- 18347932
TI  - Tumor characteristics in screen-detected and symptomatic breast cancers.
AB  - The natural course of early breast cancer has changed as a result of the
      introduction of mammographic screening. The present aim was a prospective
      analysis of screen-detected and symptomatic operable breast cancers in the era of
      mammographic service screening. The mode of detection (screen-detected,
      symptomatic or interval cancer), the type of mammographic image and other
      characteristics (the invasive tumor size, histological tumor type, grade, nodal,
      hormone receptor and HER2 status and the presence of lymphovascular invasion) of
      569 invasive breast cancers were studied. Screen-detected cancers were
      significantly more frequently of grade I, < 10 mm of size and node-negative (p <
      0.001, respectively). Symptomatic/interval cancers were significantly more
      frequently of grade 3, >20 mm of size (p < 0.001), and exhibited lymphovascular
      invasion (p = 0.001). Screening-detection of the tumor favored breast-conserving
      surgery, sentinel lymph node biopsy and the avoidance of chemotherapy (p <
      0.001). Cancers associated with casting-type calcifications on the mammogram were
      typically of ductal type (p = 0.043), of grade 2-3, estrogen receptor and
      progesterone receptor-negative and HER2-positive (p < 0.001). Interval cancers
      occurred significantly more often at a younger age and remained mammographically
      occult as compared with other cancers. Mammographic screen-detected cancers
      demonstrate more favorable prognostic features, and need less extensive treatment
      than symptomatic or interval cancers. The mammographic appearance of the tumor
      reflects its biological behavior, and this should be considered in the management
      optimization.

PMID- 18347933
TI  - BMI-1 expression is inversely correlated with the grading of renal clear cell
      carcinoma.
AB  - BMI-1 regulates cell proliferation and differentiation, is involved in stem cell
      maintenance and can act as an oncogene. We investigated BMI-1 expression in
      healthy normal kidney and in 77 renal tumours by immunohistochemistry, and
      correlated it with tumour differentiation. BMI-1 could regularly be demonstrated
      in distal tubules and in Bowman's capsule, whereas it was mostly lacking in
      proximal tubules, indicating that it may rather be a differentiation marker of
      different renal cell populations than a stem cell marker. In contrast to previous
      studies demonstrating a correlation between BMI-1 expression and malignancy, we
      showed that its expression was inversely correlated with the differentiation
      grade of clear cell carcinoma. Furthermore, despite their different biologies,
      BMI-1 was strongly expressed in both papillary carcinomas and oncocytomas. Thus,
      in renal clear cell carcinomas BMI-1 is rather a differentiation marker lost in
      carcinomas with high malignancy than an oncogene involved in tumour progression.

PMID- 18347934
TI  - Matrix metalloproteinase-9 expression in the normal mucosa-adenoma-dysplasia
      adenocarcinoma sequence of the colon.
AB  - It has been proposed that matrix metalloproteinases (MMPs) play a role in tumor
      invasion. We determined protein expression of matrix metalloproteinase-9 (MMP-9)
      in colorectal cancer (CRC), corresponding normal mucosa and colorectal adenomas.
      For confirmation of immunohistochemical results MMP-9 TaqMan RT-PCR analysis was
      performed. Expression of MMP-9 was determined on paraffin embedded biopsy
      sections by immunohistochemistry in 31 CRC patients (from cancer tissue and
      corresponding normal mucosa) and in 30 patients with adenoma (nine adenomas with
      high grade of dysplasia). MMP-9 immunostaining was determined semi
      quantitatively. For Taqman RT-PCR analyses normal mucosa (n = 5), adenoma without
      (n = 6) and with high grade dysplasia (n = 7) and CRC (n = 10) were investigated.
      Statistical analysis with ANOVA, LSD test and correlation analysis were
      performed. P value of <0.05 was considered significant. The MMP-9 expression in
      CRC was significantly higher compared to adenomas or the normal mucosa (P =
      0.001). Significantly higher expression of MMP-9 has been observed in adenomas
      with high grade dysplasia compared to other adenomas or normal colon (P < 0.001).
      Diffuse strong MMP-9 expression was present in tumor as well as in stromal cells.
      In adenoma samples, dysplastic epithelial cells showed moderate intensive
      cytoplasmic MMP-9 expression, with a clear-cut differentiation between dysplastic
      and non-dysplastic areas. Staining intensity correlated with the grade of CRC. We
      demonstrate a significantly higher expression of MMP-9 in adenoma with high grade
      dysplasia-CRC sequence as compared to normal tissue. The over-expression of MMP-9
      strongly suggests its association with colorectal carcinogenesis.

PMID- 18347935
TI  - The diagnostic value of macrophage migration inhibitory factor (MIF) in gastric
      cancer.
AB  - The present study was conducted to investigate the sensitivity, specificity,
      predictive values and accuracy of serum MIF, CEA, CA 19-9 levels and their
      various combinations in patients with gastric cancer. Study group consists of
      pathologically verified, gastric cancer (n = 63) and apparently healthy controls
      (n = 50). Serum MIF concentrations were determined by enzyme-linked immunosorbent
      assay (ELISA). Serum values of patients were significantly higher than the
      controls (p = 0.011). Diagnostic sensitivity and specificity, predictive values
      and accuracies were calculated for each marker and their various combinations.
      The best results were achieved with the marker combination of MIF-CEA-CA 19-9 and
      MIF-CEA combination. In our opinion, the combination of the markers MIF-CEA is a
      valuable diagnostic tool for gastric cancer.

PMID- 18347936
TI  - The therapeutic implications of clinically applied modifiers of heat shock
      protein 70 (Hsp70) expression by tumor cells.
AB  - Evidence that membrane-bound and extracellular heat shock proteins (HSPs) with
      molecular weights of 70 and 90 kDa are potent stimulators of the immune responses
      has accumulated over the last decade. In this review, we discuss the modulation
      of Hsp70 expression, a major stress-inducible member of the HSP70 family, in the
      cytoplasm and on the plasma membrane of tumor cells by clinically applied
      interventions such as radio- and chemotherapy.

PMID- 18347937
TI  - Location of P element insertions in the proximal promoter region of Hsp70A is
      consequential for gene expression and correlated with fecundity in Drosophila
      melanogaster.
AB  - We compared a series of Drosophila strains with P element insertions from -28 to 
      144 nucleotides 5' to the transcription start site of the Hsp70A genes
      corresponding to the range of naturally occurring P element insertion sites-to
      elucidate the consequences of insertion site for Hsp70A gene expression. Although
      all insertions reduced Hsp70A expression below that of a control strain, the
      magnitude of the reduction was inversely related to the number of nucleotides
      between the transcription start site and the insertion site. A pre-existing
      hypothesis is that naturally occurring transposable element insertions in Hsp
      promoters may be beneficial in some circumstances, which may account for their
      retention in natural populations. In the present study, in a control line heat
      shock reduced fecundity, whereas in lines with P element insertions heat shock
      typically increased fecundity. Finally, according to cluster-specific
      quantitative RT-PCR, expression of the Hsp70A cluster genes was typically greater
      than that of the Hsp70B gene cluster genes, although the latter are more numerous
      and, in this case, free of P element insertions.

PMID- 18347938
TI  - Structural and functional analysis of the HSP90AA1 gene: distribution of
      polymorphisms among sheep with different responses to scrapie.
AB  - Scrapie is a transmissible spongiform encephalopathy in sheep and goats.
      Susceptibility to this neurodegenerative disease is mainly controlled by point
      mutations at the PRNP locus. Other genes, apart from PRNP, have been reported to
      modulate resistance/susceptibility to scrapie. On the basis of several studies in
      Alzheimer and different transmissible spongiform encephalopathy models, HSP90AA1
      was chosen as a putative positional and functional candidate gene that might be
      involved in the polygenic variance mentioned above. In the present work, the
      ovine HSP90AA1 gene including the promoter and other regulatory regions has been
      isolated and characterized. Several sequence polymorphisms have also been
      identified. FISH-mapping localized the HSP90AA1 gene on ovine chromosome
      OAR19q24dist, which was confirmed by linkage analysis. This chromosome region has
      been shown to include a quantitative trait loci (QTL) for scrapie incubation
      period in sheep. Expression analyses were carried out in spleen and cerebellum
      samples. No differences in the expression of the HSP90AA1 gene were found in any
      of these tissues (p > 0.05) between control and infected animal samples.
      Nevertheless, association analyses revealed that several polymorphisms in the 5'
      and 3' regions of the HSP90AA1 gene were differentially distributed among animals
      with different responses to scrapie infection. Thus, results presented here
      support the hypothesis that HSP90AA1 could be a positional and functional
      candidate gene modulating the response to scrapie in sheep.

PMID- 18347939
TI  - Prevention of chemotherapy-induced alopecia in rodent models.
AB  - Alopecia (hair loss) is experienced by thousands of cancer patients every year.
      Substantial-to-severe alopecia is induced by anthracyclines (e.g., adriamycin),
      taxanes (e.g., taxol), alkylating compounds (e.g., cyclophosphamide), and the
      topisomerase inhibitor etoposide, agents that are widely used in the treatment of
      leukemias and breast, lung, ovarian, and bladder cancers. Currently, no treatment
      appears to be generally effective in reliably preventing this secondary effect of
      chemotherapy. We observed in experiments using different rodent models that
      localized administration of heat or subcutaneous/intradermal injection of
      geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress protein
      response in hair follicles and effectively prevented alopecia from adriamycin,
      cyclophosphamide, taxol, and etoposide. Model tumor therapy experiments support
      the presumption that such localized hair-saving treatment does not negatively
      affect chemotherapy efficacy.

PMID- 18347940
TI  - Antarctic marine molluscs do have an HSP70 heat shock response.
AB  - The success of any organism depends not only on niche adaptation but also the
      ability to survive environmental perturbation from homeostasis, a situation
      generically described as stress. Although species-specific mechanisms to combat
      "stress" have been described, the production of heat shock proteins (HSPs), such
      as HSP70, is universally described across all taxa. Members of the HSP70 gene
      family comprising the constitutive (HSC70) and inducible (HSP70) members, plus
      GRP78 (glucose-regulated protein, 78 kDa), a related HSP70 family member, were
      cloned using degenerate polymerase chain reaction (PCR) from two evolutionary
      divergent Antarctic marine molluscs (Laternula elliptica and Nacella concinna), a
      bivalve and a gastropod, respectively. The expression of the HSP70 family members
      was surveyed via quantitative PCR after an acute 2-h heat shock experiment. Both
      species demonstrated significant up-regulation of HSP70 gene expression in
      response to increased temperatures. However, the temperature level at which these
      responses were induced varied with the species (+6-8 degrees C for L. elliptica
      and +8-10 degrees C for N. concinna) compared to their natural environmental
      temperature). L. elliptica also showed tissue-specific expression of the genes
      under study. Previous work on Antarctic fish has shown that they lack the
      classical heat shock response, with the inducible form of HSP70 being permanently
      expressed with an expression not further induced under higher temperature
      regimes. This study shows that this is not the case for other Antarctic animals,
      with the two molluscs showing an inducible heat shock response, at a level
      probably set during their temperate evolutionary past.

PMID- 18347941
TI  - Low heat-shock thresholds in wild Antarctic inter-tidal limpets (Nacella
      concinna).
AB  - Heat shock proteins (HSPs) are a family of genes classically used to measure
      levels of organism stress. We have previously identified two HSP70 genes (HSP70A
      and HSP70B) in sub-tidal populations of the Antarctic limpet (Nacella concinna).
      These genes are up-regulated in response to increased seawater temperatures of 15
      degrees C or more during acute heat shock experiments, temperatures that have
      very little basis when considering the current Antarctic ecology of these
      animals. Therefore, the question was posed as to whether these animals could
      express HSP70 genes when subjected to more complex environmental conditions, such
      as those that occur in the inter-tidal. Inter-tidal limpets were collected on
      three occasions in different weather conditions at South Cove, Rothera Point,
      over a complete tidal cycle, and the expression levels of the HSP70 genes were
      measured. Both genes showed relative up-regulation of gene expression over the
      period of the tidal cycle. The average foot temperature of these animals was 3.3
      degrees C, far below that of the acute heat shock experiments. These experiments
      demonstrate that the temperature and expression levels of HSP production in wild
      animals cannot be accurately extrapolated from experimentally induced treatments,
      especially when considering the complexity of stressors in the natural
      environment. However, experimental manipulation can provide molecular markers for
      identifying stress in Antarctic molluscs, provided it is accompanied by
      environmental validation, as demonstrated here.

PMID- 18347942
TI  - Exposure of gnotobiotic Artemia franciscana larvae to abiotic stress promotes
      heat shock protein 70 synthesis and enhances resistance to pathogenic Vibrio
      campbellii.
AB  - Larvae of the brine shrimp Artemia franciscana serve as important feed in fish
      and shellfish larviculture; however, they are subject to bacterial diseases that
      devastate entire populations and consequently hinder their use in aquaculture.
      Exposure to abiotic stress was shown previously to shield Artemia larvae against
      infection by pathogenic Vibrio, with the results suggesting a mechanistic role
      for heat shock protein 70. In the current report, combined
      hypothermic/hyperthermic shock followed by recovery at ambient temperature
      induced Hsp70 synthesis in Artemia larvae. Thermotolerance was also increased as
      was protection against infection by Vibrio campbellii, the latter indicated by
      reduced mortality and lower bacterial load in challenge tests. Resistance to
      Vibrio improved in the face of declining body mass as demonstrated by measurement
      of ash-free dry weight. Hypothermic stress only and acute osmotic insult did not
      promote Hsp70 expression and thermotolerance in Artemia larvae nor was resistance
      to Vibrio challenge augmented. The data support a causal link between Hsp70
      accumulation induced by abiotic stress and enhanced resistance to infection by V.
      campbellii, perhaps via stimulation of the Artemia immune system. This
      possibility is now under investigation, and the work may reveal fundamental
      properties of crustacean immunity. Additionally, the findings are important in
      aquaculture where development of procedures to prevent bacterial infection of
      feed stock such as Artemia larvae is a priority.

PMID- 18347943
TI  - Alpha-hemoglobin-stabilizing protein (AHSP) in hemolysis, elevated liver enzyme,
      and low platelet (HELLP) syndrome, intrauterine growth restriction (IUGR) and
      fetal death.
AB  - OBJECTIVE: Alpha hemoglobin-stabilizing protein (AHSP) inhibits the production of
      reactive oxygen species in various cells, including erythrocytes. Reduced AHSP
      can mean reduced protection from stressors. Our objective was to investigate
      whether AHSP is involved in the response to stress in pregnancy. STUDY DESIGN:
      Placentas were collected from normal term pregnancies (n = 10) and pregnancies
      complicated by HELLP (n = 10), intrauterine growth restriction (IUGR; n = 10) or
      fetal death (IUFD; n = 6). AHSP messenger RNA (mRNA) and protein were determined
      using real time quantitative polymerase chain reaction (PCR) and Western blot,
      respectively. All statistical analyses were performed by using the GraphPad Prism
      Software. Differences were considered significant at p < 0.05. RESULTS: Placental
      AHSP mRNA level in HELLP (4.16E10(-4) +/- 1.77) and IUFD (4.19E10(-4) +/- 3.37)
      were significantly decreased compared with controls (28.47E10(-4) +/- 14.86; p <
      0.01), whereas levels in the IUGR group (7.55E10(-4) +/- 6.4) showed a trend
      toward being lower but the difference did not reach statistical significance.
      Western blot analysis results indicate a no significant increase of ASHP protein
      in the HELLP syndrome group and a significant decrease in the IUFD group compared
      with controls. There was no significant difference between the IUGR and control
      groups. CONCLUSION: ASHP mRNA expression in the placenta is decreased in
      complicated pregnancies, and it may be involved in the pathogenic mechanisms
      leading to the adverse pregnancy outcome.

PMID- 18347944
TI  - Changes in the regulation of heat shock gene expression in neuronal cell
      differentiation.
AB  - Neuronal differentiation of the NG108-15 neuroblastoma-glioma hybrid cells is
      accompanied by a marked attenuation in the heat shock induction of the Hsp70
      firefly luciferase reporter gene activity. Analysis of the amount and activation
      of heat shock factor 1, induction of mRNA(hsp), and the synthesis and
      accumulation of heat shock proteins (HSPs) in the undifferentiated and
      differentiated cells suggest a transcriptional mechanism for this attenuation.
      Concomitant with a decreased induction of the 72-kDa Hsp70 protein in the
      differentiated cells, there is an increased abundance of the constitutive 73-kDa
      Hsc70, a protein known to function in vesicle trafficking. Assessment of
      sensitivity of the undifferentiated and differentiated cells against stress
      induced cell death reveals a significantly greater vulnerability of the
      differentiated cells toward the cytotoxic effects of arsenite and
      glutamate/glycine. This study shows that changes in regulation of the HSP and HSC
      proteins are components of the neuronal cell differentiation program and that the
      attenuated induction of HSPs likely contributes to neuronal vulnerability whereas
      the increased expression of Hsc70 likely has a role in neural-specific functions.

PMID- 18347945
TI  - Tissue-specific targeting of Hsp26 has no effect on heat resistance of neural
      function in larval Drosophila.
AB  - Hsp26 belongs to the small heat-shock protein family and is normally expressed in
      all cells during heat stress. We aimed to determine if overexpression of this
      protein protects behavior and neural function in Drosophila melanogaster during
      heat stress, as has previously been shown for Hsp70. We used the UAS-GAL4
      expression system to drive expression of Hsp26 in the whole animal
      (ubiquitously), in the motoneurons, and in the muscles of wandering third-instar
      larvae. There were slight increases in time to crawling failure and normalized
      excitatory junction potential (EJP) area for some of the transgenic lines, but
      these were not consistent. In addition, Hsp26 had no effect on the temperature at
      failure of EJPs, normalized EJP peak amplitude, and normalized EJP half-width.
      Overexpression larvae had a similar number of motoneuronal boutons and length of
      nerve terminals as controls, indicating that the occasional protective effects on
      locomotion were not due to changes at the synapse. We conclude that
      overexpression had a small thermoprotective effect on locomotion and no effect on
      neural function. As it has been shown that Hsp26 requires action of other Hsps to
      reactivate the denatured proteins to which it binds, we propose that at least in
      larvae, the function of Hsp26 was masked in the relative absence of other Hsps.

PMID- 18347946
TI  - Substitution of only two residues of human Hsp90alpha causes impeded dimerization
      of Hsp90beta.
AB  - Two isoforms of the 90-kDa heat-shock protein (Hsp90), i.e., Hsp90alpha and
      Hsp90beta, are expressed in the cytosol of mammalian cells. Although Hsp90
      predominantly exists as a dimer, the dimer-forming potential of the beta isoform
      of human and mouse Hsp90 is less than that of the alpha isoform. The 16 amino
      acid substitutions located in the 561-685 amino acid region of the C-terminal
      dimerization domain should be responsible for this impeded dimerization of
      Hsp90beta (Nemoto T, Ohara-Nemoto Y, Ota M, Takagi T, Yokoyama K. Eur J Biochem
      233: 1-8, 1995). The present study was performed to define the amino acid
      substitutions that cause the impeded dimerization of Hsp90beta. Bacterial two
      hybrid analysis revealed that among the 16 amino acids, the conversion from
      Ala(558) of Hsp90beta to Thr(566) of Hsp90alpha and that from Met(621) of
      Hsp90beta to Ala(629) of Hsp90alpha most efficiently reversed the dimeric
      interaction, and that the inverse changes from those of Hsp90alpha to Hsp90beta
      primarily explained the impeded dimerization of Hsp90beta We conclude that taken
      together, the conversion of Thr(566) and Ala(629) of Hsp90alpha to Ala(558) and
      Met(621) is primarily responsible for impeded dimerization of Hsp90beta.

PMID- 18347947
TI  - Surface expression of Hsp70B' in response to proteasome inhibition in human colon
      cells.
AB  - Hsp70B' was expressed on the surface of HT-29 and CRL-1809 but not SW-480 human
      colon cell lines in response to proteasome inhibition as detected using flow
      cytometry. Surface expression was not detected under non-stress conditions nor
      was heat shock an inducer of surface expression in the three cell lines tested.
      Phylogenetic analysis indicated that the Hsp70B' protein sequence was most
      closely related to another major inducible human Hsp70, Hsp72. Hsp70B' appeared
      to be recently diverged, as homologs for Hsp70B' have not been found in rodents.
      Hsp72 and Hsp70B' shared 100% amino acid sequence identity in their predicted
      peptide-binding regions suggesting that they bind the same peptide substrates,
      perhaps in extracellular antigen presentation. Amino acid sequence differences
      were concentrated in the lid regions and the C-terminal domains raising the
      possibility that Hsp72 and Hsp70B' bind different co-chaperones or cell surface
      receptors.

PMID- 18347948
TI  - PCR-based detection of Pol III-transcribed transposons and its application to the
      rodent model of ultraviolet response.
AB  - Cellular levels of RNAs containing transposable elements increase in response to
      various stresses. Polymerase III (Pol III)-dependent transcripts of transposons
      are different from transposon-containing RNAs generated by read-through Pol II
      dependent transcription. Until now, Pol III transcripts were detected by primer
      extension followed by time-consuming gel electrophoresis. In this paper, we
      describe a more sensitive PCR-based method for the selective detection of Pol III
      transcribed RNAs. The method is based on the difference in sequences at the 5'
      ends of the Pol II- and Pol III-dependent transcripts. We employed this method to
      quantify Pol III transcripts of transposon B1 in rodent cells and revealed that
      their levels are affected by UV irradiation. We therefore conclude that the
      abundance of the Pol III-transcribed fraction of cellular RNA may serve as marker
      of stress response and can be conveniently quantified by the method described.

PMID- 18347949
TI  - Study on physicochemical properties and in vitro bioactivity of tricalcium
      silicate-calcium carbonate composite bone cement.
AB  - In this article, a novel bone cement composed of tricalcium silicate
      (Ca(3)SiO(5); C(3)S) and calcium carbonate (CaCO(3)) was prepared with the weight
      percent of CaCO(3) in the range of 0, 10, 20, 30, and 40%. The initial setting
      time was dramatically reduced from 90 to 45 min as the content of CaCO(3)
      increased from 0 to 40%, and the workable paste with a liquid/powder (L/P) ratio
      of 0.8 ml/g could be injected between 2 and 20 min (nozzle diameter 2.0 mm). The
      composite cement showed higher mechanical strength (24-27 MPa) than that of the
      pure Ca(3)SiO(5) paste (14-16 MPa). Furthermore, the composite cement could
      induce apatite formation and degrade in the phosphate buffered saline. The
      results indicated that the Ca(3)SiO(5)-CaCO(3) paste had better hydraulic
      properties than pure Ca(3)SiO(5) paste, and also the composite cement was
      bioactive and degradable. The novel bone cement could be a potential candidate as
      a bone substitute.

PMID- 18347950
TI  - Influence of pore size on tensile strength, permeability and porosity of
      hyaluronan-collagen scaffolds.
AB  - Recent investigations have shown the importance of scaffold pore size on the
      realisation of tissue engineered cartilage which promotes cell adhesion,
      proliferation and differentiation. The objective of this study was to investigate
      the influence of pore size on the mechanical properties, the permeability and the
      porosity of hyaluronan-collagen scaffolds. Hyaluronan-collagen scaffolds with
      three different mean pore sizes (302.5, 402.5 and 525 microm) have been produced
      according to a standardised protocol. The maximum stress at rupture, the Young's
      Moduli, permeability and porosity of the scaffolds were investigated. The
      permeability was determined both empirically and mathematically. Increased pore
      sizes indicated a larger stress at rupture as well as increased Young's Moduli.
      Porosity and permeability were raised by increasing pore sizes. The
      mathematically calculated permeability showed the same trend. The results
      indicate a higher mechanical stability for scaffolds with larger pores. The
      experimental and mathematical experiments both show increased permeability and
      fluid mobility for larger pores in scaffolds. Morphological changes resulting
      from the alteration of pore size led to non-correlation between the calculated
      and the experimental permeability.

PMID- 18347951
TI  - Design of dental implants, influence on the osteogenesis and fixation.
AB  - The fixation and the bone ingrowth at the interface of porous cylindrical
      implants (total porosity of 37% and average pores diameter of 480 microm) were
      compared in vivo to rough cylindrical implants (R (a) = 5.3 microm), both of
      commercially pure titanium, made by powder metallurgy. The implants were inserted
      into the tibias of 20 rabbits and the animals were sacrificed 4 and 8 weeks after
      surgery. The percentage of bone-implant contact observed in porous implant was
      significantly larger than in the rough ones for all of sacrifice periods,
      respectively, 57% vs. 46% after 4 weeks, and 59% vs. 50% after 8 weeks. The
      mechanical tests showed a significant increase in the shear strength of the
      porous implants for the two analyzed periods, 4 and 8 weeks (14 and 20 MPa), when
      compared with rough ones (4 and 13 MPa). These results suggest that porous
      implants improve the contact at the implant-bone interface and increase the
      fixation to the bone, improving the osseointegration. Thus, the porous implant
      might be an alternative to dental implant in less favorable conditions, and
      appear to be better fixed to bone, offering promising alternatives.

PMID- 18347952
TI  - On the possibility of silicon nitride as a ceramic for structural orthopaedic
      implants. Part I: processing, microstructure, mechanical properties,
      cytotoxicity.
AB  - Notwithstanding the good combination of mechanical and tribological properties,
      the suitability of silicon nitride for application as prosthesis in bone
      reconstruction or in articular joints replacements is still controversial. This
      study aims to design and produce three different silicon nitride-based ceramics
      and to test the materials. In this Part I the microstructure and mechanical
      properties evidence outstanding characteristics and the cytotoxicity studies
      confirm that all the materials are extremely inert and biocompatible. In Part II,
      the wear performance and the wettability and chemical stability against different
      aqueous media and physiological solutions are investigated and discussed.

PMID- 18347953
TI  - An amidated carboxymethylcellulose hydrogel for cartilage regeneration.
AB  - An amidic derivative of carboxymethylcellulose was synthesized (CMCA). The new
      polysaccharide was obtained by converting a large percentage of carboxylic groups
      ( approximately 50%) of carboxymethylcellulose into amidic groups rendering the
      macromolecule quite similar to hyaluronan. Then, the polysaccharide (CMCA) was
      crosslinked. The behavior of CMCA hydrogel towards normal human articular
      chondrocytes (NHAC) was in vitro studied monitoring the cell proliferation and
      synthesis of extra cellular matrix (ECM) components and compared with a
      hyaluronan based hydrogel (Hyal). An extracellular matrix rich in cartilage
      specific collagen and proteoglycans was secreted in the presence of hydrogels.
      The injectability of the new hydrogels was also analysed. An experimental in vivo
      model was realized to study the effect of CMCA and Hyal hydrogels in the
      treatment of surgically created partial thickness chondral defects in the rabbit
      knee. The preliminary results pointed out that CMCA hydrogel could be considered
      as a potential compound for cartilage regeneration.

PMID- 18347954
TI  - Effect of the molecular weight of polyethylene glycol (PEG) on the properties of
      chitosan-PEG-poly(N-isopropylacrylamide) hydrogels.
AB  - Our prior study has shown that polyethylene glycol (PEG) played a crucial role in
      improving the properties of the physically crosslinked chitosan-PEG-poly(N
      isopropylacrylamide) (PNIPAAm) hydrogels. In this paper, we further investigated
      the effect of the molecular weight (MW) of PEG on the properties of the chitosan
      based physical hydrogels. Fourier Transform Infrared Spectroscopy (FTIR) study
      showed that the interaction between PEG and other components in the physically
      crosslinked hydrogels became stronger as the MW of PEG increased. The wide angle
      X-ray diffraction (WAXD) study indicated that the crystallinity of the physical
      hydrogels decreased with an increase in the MW of PEG. The thermal study using
      differential scanning calorimetry (DSC) revealed the crystallizability of the
      physical hydrogels first reduced with an increase in the MW of PEG, but slightly
      increased thereafter with a further increase in the MW of PEG. The swelling test
      showed the water uptake capability of the physical hydrogels increased with an
      increase in the MW of PEG. The results obtained by scanning electron microscope
      (SEM) found that the morphological changes of the physical hydrogels with MW of
      PEG were consistent with the results of swelling and thermal properties; and,
      contrary to pure PNIPAAm hydrogels which showed a compact and dense network
      structure at a temperature (37 degrees C) above its LCST, the physical chitosan
      PEG-PNIPAAm hydrogels exhibited porous network structure at 37 degrees C instead.
      The mechanical property of the physical hydrogels was initially increased with an
      increase in PEG MW, but deteriorated with a further increase in PEG MW.
      Therefore, the MW of PEG played a key role in controlling the property of the
      chitosan-based physical hydrogels.

PMID- 18347955
TI  - Synthesis and characterization of nanoporous SiO(2)/pHEMA biocomposites.
AB  - Porous SiO(2)/pHEMA biocomposites were synthesized in situ by incorporating
      silica nanoparticles with a hydroxyethyl methacrylate (HEMA) monomer, following a
      UV-induced photopolymerization. The nanostructure of the composites was
      characterized and the resulting physical properties were examined. The release
      kinetics of the model molecule-vitamin B12-and the hemocompatibility of the
      porous SiO(2)/pHEMA composites were investigated. Heterogeneous reaction kinetics
      is proposed to be the formation mechanism of the nanoporosity in the pHEMA matrix
      as a result of incorporating silica nanoparticles following photopolymerization.
      Experimental results also demonstrated that the incorporation of the silica
      nanoparticles into the pHEMA matrix not only enhanced the mechanical property but
      also maintained a good hemocompatibility of the resulting biocomposites. In
      addition, it was observed that the drug release profile of the composites (in the
      form of a membrane) can be precisely regulated from a two-stage pattern to one
      stage pattern by varying the concentration of both the SiO(2) nanoparticles and
      HEMA monomer during synthesis. The permeability of the model drug was enhanced by
      two orders of magnitude from 4.22 x 10(-7 )cm(2)/h to 3.92 x 10(-5 )cm(2)/h by
      controlling the micro-to-nanostructure of the composites. The platelet adhesion
      experiment demonstrated low aggregation of the platelets on the surface of the
      biocomposite membranes, indicating a promising antithrombotic property.

PMID- 18347958
TI  - Surface modified single molecules free-diffusion evidenced by fluorescence
      correlation spectroscopy.
AB  - We report on the free diffusion of single molecule near an interface studied
      using fluorescence correlation spectroscopy. In particular, we show that the
      chemical nature of the substrate may modify the free diffusion of a widely used
      molecule (rhodamine 6G), thus inducing unexpected effects in fluorescence
      correlation spectroscopy measurements. Our results show a strong influence, up to
      a few micrometer from the interface, of the surface polarity. This effect is
      assessed through the relative weight of the two dimensions diffusion process
      observed close to the surface. Our results are discussed in terms of competition
      between surface-solvent, solvent-molecule and molecule-surface specific
      interactions.

PMID- 18347959
TI  - Modified donor lymphocyte infusion (DLI) for the prophylaxis of leukemia relapse
      after hematopoietic stem cell transplantation in patients with advanced leukemia-
      feasibility and safety study.
AB  - PURPOSE: We retrospectively evaluated the feasibility and safety of a modified
      prophylactic donor lymphocytes infusion (DLI) approach in advanced leukemia.
      MATERIALS AND METHODS: Thirty-three patients with advanced leukemia received
      modified prophylactic DLI; that is, granulocyte colony-stimulating factor-primed
      peripheral blood progenitor cells instead of steady-donor lymphocyte harvests
      were used, and a short-term immunosuppressive agent (cyclosporine A or
      methotrexate 10 mg once per week for 2 to 4 weeks) was used for prevention of DLI
      associated graft versus host disease (GVHD) after human leukocyte antigen
      identical sibling hematopoietic stem cell transplantation. RESULTS: Thirty-nine
      infusions were performed in 33 patients. The mononuclear cells and median CD3+
      cells infused for DLI were 1-2 x 10(8) and 0.93 x 10(6) per kilogram,
      respectively. Six patients experienced II-IV-grade acute GVHD. Twenty patients
      developed chronic GVHD. No GVHD-related death or transfusion-related pancytopenia
      was observed. With an 18-month median follow-up, 16 patients were in disease-free
      survival, and overall survival at 1 and 1.5 years was 69.0% and 50.2%,
      respectively. CONCLUSION: The modified prophylactic DLI strategy might represent
      a step forward in the treatment of advanced leukemia.

PMID- 18347960
TI  - A time to change our minds: anthropology and psychiatry in the 21st century.

PMID- 18347961
TI  - Psychiatry and military conscription in Brazil: the search for opportunity and
      institutionalized therapy.
AB  - Since the fall of the Brazilian military dictatorship in 1984, a number of
      structural and ideological changes associated with demilitarization and democracy
      have changed the face of psychiatric theory and practice. Around the country,
      pockets of innovative, politically sensitive and Marxist-inspired community-based
      forms of "psi" practice are developing. This emergent psi movement is making a
      range of positive contributions to the lives of average citizens, including those
      of poor disenfranchized youth. This paper, however, explores one particular
      dimension of the work of psi practitioners that has proven antithetical to the
      psi community's current politicized community-based aims. Based on qualitative
      and quantitative longitudinal ethnographic fieldwork with therapists and young
      men in Pelotas, this paper analyzes how certain kinds of psi interventions being
      carried out in schools for a subset of lower-class young men during their early
      teen years are encouraging some youth to seek military training as a life option.
      Although these young men initially had quite captivating, engaged and politicized
      if also conflicting-interactions with therapists, their eventual disillusionment
      with their therapeutic and scholastic experiences resulted in high levels of
      social alienation and de-politicization. In these young men's search for what can
      best be described as formulaic solutions to troubling psychological experiences
      associated with a tumultuous institutionalized transition to adulthood, military
      training came to represent a form of self-cultivation and self-therapy. Several
      youth also hoped military training would enable them to actively disengage with
      local political processes and find shelter from troubling social inequities and
      injustice. The paper ends by reviewing the implications of these results for the
      future of psi knowledge and practice in Brazil.

PMID- 18347962
TI  - Experiences of teens living in the shadow of Huntington Disease.
AB  - Research on families with Huntington Disease (HD) has primarily focused on adult
      decision-making surrounding predictive genetic testing and caregiver stress.
      Little is known about the experiences of teens living in these families. This
      qualitative study explored the experiences of 32 teens living in families with
      HD. Six focus groups were conducted across the U.S. and Canada. Data were
      analyzed using descriptive qualitative analysis. Huntington disease appeared to
      cast a shadow over the experiences described by teens. Four themes were
      identified: watching and waiting; alone in the midst of others; family life is
      kind of hard; and having to be like an adult. These experiences highlight the
      need for genetic counselors, health care providers, and school personnel to be
      aware of issues facing teens living in families with HD. Recognizing patterns of
      teen experiences may help health care providers develop strategies to support
      coping by teens in HD families.

PMID- 18347963
TI  - C-reactive protein is linked to lower cognitive performance in overweight and
      obese women.
AB  - Our objective was to ascertain the nature of the associations between C-reactive
      protein (CRP) and cognition, and to examine how they are affected by gender and
      obesity. We evaluated 62 females and 63 males between 42 and 82 years of age.
      There were 20 lean females with a body mass index (BMI) of <25 kg/m2 and 42
      overweight or obese females, with BMIs > or =25 kg/m2. There were 14 lean males
      and 49 with BMIs >/=25 kg/m2. CRP was associated with lower scores on cognitive
      tests of frontal lobe function among females and these associations were driven
      by the overweight/obese female group. In these data no associations between CRP
      and cognition were found among males. Obesity-associated inflammation is much
      more prominent in females and it appears to be associated with cognitive
      dysfunction, particularly of frontal lobe tasks.

PMID- 18347964
TI  - Nitrate therapy in acute myocardial infarction: potion or poison?

PMID- 18347965
TI  - Use of insulin to improve glycemic control in diabetes mellitus.
AB  - BACKGROUND: The restoration of normoglycemia ensures the control of diabetic
      symptoms and reduction in microangiopathic complications in type 1 and type 2
      diabetes. However, there is no conclusive evidence that intensive glycemic
      control alone will prevent macrovascular disease, the commonest cause of
      morbidity and mortality in type 2 diabetes. As atherosclerosis is an inflammatory
      condition, it is relevant that the two common insulin resistant states of obesity
      and type 2 diabetes have significant inflammatory processes, which promote
      atherosclerosis. It is also relevant that glucose has been shown to have profound
      effects on the endothelial cell, the leukocyte and the platelet. These effects
      include the induction of acute oxidative and inflammatory stress and a
      prothrombotic and pro-apoptotic effect following glucose intake. In contrast
      insulin has been shown to exert several biological effects at physiologically
      relevant concentrations, in relation to the endothelial cell, the platelet and
      leucocyte function, which may be cardioprotective and potentially anti
      atherosclerotic. CONCLUSION: These findings are of great interest as it is
      possible that the prevention of macrovascular complications in type 2 diabetes
      may require the use of those glucose lowering drugs which have additional anti
      inflammatory effects in addition to the control of comorbid conditions
      (hypertension and dyslipidemia) associated with this disease. Results of future
      clinical trials are awaited to confirm the benefits of this approach in the
      primary and secondary prevention of macrovascular complications in type 2
      diabetes.

PMID- 18347966
TI  - Topographic ERP analyses: a step-by-step tutorial review.
AB  - In this tutorial review, we detail both the rationale for as well as the
      implementation of a set of analyses of surface-recorded event-related potentials
      (ERPs) that uses the reference-free spatial (i.e. topographic) information
      available from high-density electrode montages to render statistical information
      concerning modulations in response strength, latency, and topography both between
      and within experimental conditions. In these and other ways these topographic
      analysis methods allow the experimenter to glean additional information and
      neurophysiologic interpretability beyond what is available from canonical
      waveform analyses. In this tutorial we present the example of somatosensory
      evoked potentials (SEPs) in response to stimulation of each hand to illustrate
      these points. For each step of these analyses, we provide the reader with both a
      conceptual and mathematical description of how the analysis is carried out, what
      it yields, and how to interpret its statistical outcome. We show that these
      topographic analysis methods are intuitive and easy-to-use approaches that can
      remove much of the guesswork often confronting ERP researchers and also assist in
      identifying the information contained within high-density ERP datasets.

PMID- 18347967
TI  - Emotional pre-eminence of human vocalizations.
AB  - Human vocalizations (HV), as well as environmental sounds, convey a wide range of
      information, including emotional expressions. The latter have been relatively
      rarely investigated, and, in particular, it is unclear if duration-controlled non
      linguistic HV sequences can reliably convey both positive and negative emotional
      information. The aims of the present psychophysical study were: (i) to generate a
      battery of duration-controlled and acoustically controlled extreme valence
      stimuli, and (ii) to compare the emotional impact of HV with that of other
      environmental sounds. A set of 144 HV and other environmental sounds was selected
      to cover emotionally positive, negative, and neutral values. Sequences of 2 s
      duration were rated on Likert scales by 16 listeners along three emotional
      dimensions (arousal, intensity, and valence) and two non-emotional dimensions
      (confidence in identifying the sound source and perceived loudness). The 2 s
      stimuli were reliably perceived as emotionally positive, negative or neutral. We
      observed a linear relationship between intensity and arousal ratings and a
      "boomerang-shaped" intensity-valence distribution, as previously reported for
      longer, duration-variable stimuli. In addition, the emotional intensity ratings
      for HV were higher than for other environmental sounds, suggesting that HV
      constitute a characteristic class of emotional auditory stimuli. In addition,
      emotionally positive HV were more readily identified than other sounds, and
      emotionally negative stimuli, irrespective of their source, were perceived as
      louder than their positive and neutral counterparts. In conclusion, HV are a
      distinct emotional category of environmental sounds and they retain this
      emotional pre-eminence even when presented for brief periods.

PMID- 18347968
TI  - Genetic and environmental influences on individual differences in attitudes
      toward homosexuality: an Australian twin study.
AB  - Previous research has shown that many heterosexuals hold negative attitudes
      toward homosexuals and homosexuality (homophobia). Although a great deal of
      research has focused on the profile of homophobic individuals, this research
      provides little theoretical insight into the aetiology of homophobia. To examine
      genetic and environmental influences on variation in attitudes toward homophobia,
      we analysed data from 4,688 twins who completed a questionnaire concerning sexual
      behaviour and attitudes, including attitudes toward homosexuality. Results show
      that, in accordance with literature, males have significantly more negative
      attitudes toward homosexuality than females and non-heterosexuals are less
      homophobic than heterosexuals. In contrast with some earlier findings, age had no
      significant effect on the homophobia scores in this study. Genetic modelling
      showed that variation in homophobia scores could be explained by additive genetic
      (36%), shared environmental (18%) and unique environmental factors (46%).
      However, corrections based on previous findings show that the shared
      environmental estimate may be almost entirely accounted for as extra additive
      genetic variance arising from assortative mating for homophobic attitudes. The
      results suggest that variation in attitudes toward homosexuality is substantially
      inherited, and that social environmental influences are relatively minor.

PMID- 18347969
TI  - Divergent physical activity and novel alternative responses to high fat feeding
      in polygenic fat and lean mice.
AB  - We determined whether altered physical activity levels might underlie the
      contrasting adiposity of a divergently selected polygenic murine model of
      metabolic syndrome (Fat; F) and leanness (Lean; L) mice. We measured physical
      activity with a long term running wheel experiment and performed an additional
      high fat diet intervention. Further, we measured posture allocation by visual
      monitoring within the home cage as a non-exercise correlate of 'normal' physical
      activity. Whilst initially similar, running wheel activity of the F line declined
      with age, while the activity of the L line increased. Food intake was higher in
      the L line and increased with wheel exposure. Vertical rearing measured by video
      quantification in the home cage, without the stimulus of a running wheel was also
      significantly higher in the L line. The two lines developed novel alternate
      strategies to defend their body weight when exposed to high fat diets with a
      running wheel. F mice increased their running wheel activity, and despite
      unaltered food intake, still gained weight. L mice reduced their food intake and
      maintained activity levels without a significant change in body weight.
      Phenotypic selection for divergence in body fat content has co-segregated with a
      genetic predisposition for divergent physical activity levels and different
      strategies for coping with exposure to high fat diets that will facilitate the
      discovery of the genes underlying these important obesity related traits.

PMID- 18347970
TI  - Do schools moderate the genetic determinants of smoking?
AB  - This paper uses data from the National Longitudinal Study of Adolescent Health to
      examine the extent to which school-level social and institutional factors
      moderate genetic tendencies to smoke cigarettes. Our analysis relies on a sub
      sample of 1,198 sibling and twin pairs nested within 84 schools. We develop a
      multilevel modeling extension of regression-based quantitative genetic techniques
      to calculate school-specific heritability estimates. We show that smoking onset
      (h2 = .51) and daily smoking (h2 = .58) are both genetically influenced. Whereas
      the genetic influence on smoking onset is consistent across schools, we show that
      schools moderate the heritability of daily smoking. The heritability of daily
      smoking is the highest within schools in which the most popular students are also
      smokers and reduced within schools in which the majority of the students are non
      Hispanic and white. These findings make important contributions to the literature
      on gene-environment interactions.

PMID- 18347971
TI  - MicroRNA expression in preimplantation mouse embryos from Ped gene positive
      compared to Ped gene negative mice.
AB  - PURPOSE: The mouse preimplantation embryo development (Ped) gene product, Qa-2,
      influences the rate of preimplantation embryonic development and overall
      reproductive success. Here we investigated the expression pattern of two
      microRNAs, miR-125a and miR-125b, known to be involved in development in lower
      organisms, in preimplantation embryos from the two-cell, four-cell, eight-cell,
      morula, and blastocyst stages of development from the congenic B6.K1 (Ped
      negative) and B6.K2 (Ped positive) strains of mice. METHOD: B6.K1 and B6.K2
      congenic mice differ only in the absence (B6.K1) or presence (B6.K2) of the genes
      encoding Qa-2 protein. We analyzed the expression of miR-125a and miR-125b in
      B6.K1 and B6.K2 preimplantation embryos by using real-time PCR. RESULT: We found
      no variability in miR-125b expression at any developmental stage in both strains.
      However, miR-125a expression increased during development in both strains and was
      ten times higher in Ped negative (B6.K1) embryos than in Ped positive (B6.K2)
      embryos by the blastocyst stage of development. CONCLUSION: Our results show that
      the absence of the Ped gene profoundly affects the level of a miRNA (miR-125a)
      known to regulate early development. The implication is that miR-125a is likely
      involved in the regulation of timing of early development in mice.

PMID- 18347972
TI  - Longitudinal changes in intellectual development in children with Fragile X
      syndrome.
AB  - Structural equation modeling (SEM) was used to examine the development of
      intellectual functioning in 145 school-age pairs of siblings. Each pair included
      one child with Fragile X syndrome (FXS) and one unaffected sibling. All pairs of
      children were evaluated on the Wechsler Intelligence Scale for Children-Third
      Edition (WISC-III) at time 1 and 80 pairs of children received a second
      evaluation at time 2 approximately 4 years later. Compared to their unaffected
      siblings, children with FXS obtained significantly lower percentage correct
      scores on all subtests of the WISC at both time points. During the time between
      the first and second assessments, the annual rate of intellectual development was
      approximately 2.2 times faster in the unaffected children compared to the
      children with FXS. Levels of the fragile X mental retardation protein (FMRP) were
      highly associated with intellectual ability scores of the children with FXS at
      both time points (r=0.55 and 0.64 respectively). However, when gender, age, and
      the time between assessments were included as covariates in the structural
      equation model, FMRP accounted for only 5% of the variance in intellectual
      ability scores at time 1 and 13% of the variance at time 2. The results of this
      study suggest that slower learning contributes to the low and declining
      standardized IQ scores observed in children with FXS.

PMID- 18347973
TI  - The shifting subtypes of ADHD: classification depends on how symptom reports are
      combined.
AB  - Research on the correlates of ADHD subtypes has yielded inconsistent findings,
      perhaps because the procedures used to define subtypes vary across studies. We
      examined this possibility by investigating whether the ADHD subtype distribution
      in a community sample was sensitive to different methods for combining informant
      data. We conducted a study to screen all children in grades 1-5 (N = 7847) in a
      North Carolina County for ADHD. Teachers completed a DSM-IV behavior rating scale
      and parents completed a structured telephone interview. We found substantial
      differences in the distribution of ADHD subtypes depending on whether one or both
      sources were used to define the subtypes. When parent and teacher data were
      combined, the procedures used substantially influenced subtype distribution. We
      conclude the ADHD subtype distribution is sensitive to how symptom information is
      combined and that standardization of the subtyping process is required to advance
      our understanding of the correlates of different ADHD subtypes.

PMID- 18347974
TI  - Immediate effect of specific nostril manipulating yoga breathing practices on
      autonomic and respiratory variables.
AB  - The effect of right, left, and alternate nostril yoga breathing (i.e., RNYB,
      LNYB, and ANYB, respectively) were compared with breath awareness (BAW) and
      normal breathing (CTL). Autonomic and respiratory variables were studied in 21
      male volunteers with ages between 18 and 45 years and experience in the yoga
      breathing practices between 3 and 48 months. Subjects were assessed in five
      experimental sessions on five separate days. The sessions were in fixed possible
      sequences and subjects were assigned to a sequence randomly. Each session was for
      40 min; 30 min for the breathing practice, preceded and followed by 5 min of
      quiet sitting. Assessments included heart rate variability, skin conductance,
      finger plethysmogram amplitude, breath rate, and blood pressure. Following RNYB
      there was a significant increase in systolic, diastolic and mean pressure. In
      contrast, the systolic and diastolic pressure decreased after ANYB and the
      systolic and mean pressure were lower after LNYB. Hence, unilateral nostril yoga
      breathing practices appear to influence the blood pressure in different ways.
      These effects suggest possible therapeutic applications.

PMID- 18347975
TI  - Anti-oligosaccharide antibodies as tools for studying sulfated
      sialoglycoconjugate ligands for siglecs and selectins.
AB  - Several sulfated sialoglycoconjugates have recently been shown to serve as
      ligands for selectins and siglecs. For instance, alpha2-->3 sialylated 6-sulfo
      Lewis x was found to serve as a ligand for selectins on skin-homing helper memory
      T cells, and alpha2-->6 sialylated 6-sulfo-LacNAc to be a preferred ligand for
      CD22/siglec-2 on human naive B cells. Monoclonal antibodies specific to sulfated
      sialoglycoconjugates are effective tools to dissect these ligands on minor
      subsets of human leukocytes.

PMID- 18347976
TI  - The markers of inflammation and endothelial dysfunction in correlation with
      glycated haemoglobin are present in type 2 diabetes mellitus patients but not in
      their relatives.
AB  - The aim of this study is to test several biomarkers of inflammation, of
      endothelial dysfunction, glycated haemoglobin, and their reflection in arterial
      dilatation, in patients with type 2 diabetes mellitus and in their relatives, in
      order to demonstrate if relatives present markers as a form of precocious
      indicators of diabetes mellitus. Individuals between 30 and 55 years of age and
      without clinical arterial disease were divided in three groups: type 2 diabetes
      mellitus patients without complications (12 men and 18 women); first degree
      relatives of type 2 diabetes mellitus (14 men and 20 women); and control
      individuals (9 men and 16 women). Body composition was measured with a
      bioelectrical impedance analyzer and endothelial function with an eco-Doppler
      device. We determined glucose, insulin, C-peptide, glycated haemoglobin,
      fibrinogen, E-selectin, P-selectin, soluble intercellular cell adhesion molecule
      1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL
      6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) in
      plasma. We also studied endothelium independent dilatation and endothelium
      dependent dilatation. THE RESULTS: ICAM-1 and VCAM-1 were significantly higher in
      the diabetic group (237.5+/-43.4 and 692.5+/-168.6 ng/l) than in controls
      (197.4+/-51.2 and 573.5+/-121.1 ng/l, p=0.011 and 0.013, respectively), but were
      not higher in the family group (224.5+/-45.2 and 599.8+/-150.4 ng/l). CRP was
      higher in the diabetic group (3.35+/-3.27 mg/l) than in the other groups (1.28+/
      1.29 and 1.61+/-1.54 mg/l, p=0.002) and correlated with glycated haemoglobin. The
      non-endothelium mediated dilatation was lesser in the diabetic group than in the
      family group (17.3+/-6.1 vs. 24+/-8, p=0.029) and controls. In conclusion
      patients with uncomplicated type 2 diabetes, but not their relatives, have
      biochemical markers of sub-clinical inflammation in relationship with glycated
      haemoglobin and dysfunction of the endothelial cells markers. In these patients
      endothelium independent dilatation is more affected than endothelium dependent
      dilatation.

PMID- 18347977
TI  - Versatile strategy for the synthesis of biotin-labelled glycans, their
      immobilization to establish a bioactive surface and interaction studies with a
      lectin on a biochip.
AB  - The emerging role of glycans as versatile biochemical signals in diverse aspects
      of cellular sociology calls for establishment of sensitive methods to monitor
      carbohydrate recognition by receptors such as lectins. Most of these techniques
      involve the immobilization of one of the binding partners on a surface, e.g.
      atomic force microscopy, glycan array and Surface Plasmon Resonance (SPR), hereby
      simulating cell surface presentation. Here, we report the synthesis of
      fluorescent glycoconjugates, with a functionalization strategy which avoids the
      frequently occurring ring opening at the reducing end for further immobilization
      on a surface or derivatization with biotin. In order to improve the versatility
      of these derivatized glycans for biological studies, a new approach for the
      synthesis of biotinylated and fluorescent glycans has also been realized.
      Finally, to illustrate their usefulness the neoglycoconjugates were immobilized
      on different surfaces, and the interaction analysis with a model lectin, the
      toxin from mistletoe, proved them to act as potent ligands, underscoring the
      merit of the presented synthetic approach.

PMID- 18347978
TI  - Intracellular devastation in heart failure.
AB  - End-stage heart failure is characterized by a number of abnormalities at the
      cellular level, which include changes in excitation-contraction coupling,
      alterations in contractile proteins and activation/deactivation of signaling
      pathways. Even though many of these changes are adaptive to the high workload and
      stress in heart failure, a significant number of these alterations are deeply
      deleterious to the cardiac cell. In this article, we will review the changes in
      calcium cycling that occur in myopathic hearts and how they can be effectively
      targeted. We will also focus on protein misfolding in the setting of cardiac
      dysfunction.

PMID- 18347979
TI  - Sensitivity of a system of care in recognizing communication disorders in
      children with serious emotional disorders.
AB  - This study evaluated the sensitivity and specificity of a system of care (SOC) in
      identifying communication disorders in children with serious emotional disorders
      (SED). Speech/language screenings were completed on 39 children. Children showing
      possible communication disorders received comprehensive speech-language
      evaluations. Records were reviewed for communication disorders suspected and
      identified by the SOC and for services provided. Results showed that the SOC was
      poor in identifying communication disorders in children with SED. This study
      underscores the importance of SOCs addressing the needs for appropriate
      identification and treatment of communication disorders in children with SED.

PMID- 18347980
TI  - Physical wellness and employment status among adults with serious mental illness.
AB  - This study examined whether concurrent medical status contributes to employment
      outcomes among those with psychiatric disabilities. Thirty-five percent (n = 70)
      of the 200 participants reported being currently employed. Sixty-three percent (n
      = 127) reported one or more co-occurring medical conditions; thirty-six percent
      (n = 71) reported two or more, and twenty-one percent (n = 41) reported three or
      more co-occurring medical conditions. Individuals with higher self-ratings of
      physical health functioning were more likely to be employed. Neither the number
      of co-occurring medical conditions nor any specific medical condition was related
      to employment status. Recommendations to enhance existing models of supported
      employment programs with physical health and wellness promotion components are
      offered.

PMID- 18347981
TI  - CYP1B1 polymorphisms and k-ras mutations in patients with pancreatic ductal
      adenocarcinoma.
AB  - The frequency of CYP1B1 polymorphisms in pancreatic cancer has never been
      reported. There is also no evidence on the relationship between CYP1B1 variants
      and mutations in ras genes (K-, H- or N-ras) in any human neoplasm. We analyzed
      the following CYP1B1 polymorphisms in 129 incident cases of pancreatic ductal
      adenocarcinoma (PDA): the m1 allele (Val to Leu at codon 432) and the m2 allele
      (Asn to Ser at codon 453). The calculated frequencies for the m1 Val and m2 Asn
      alleles were 0.45 and 0.68, respectively. CYP1B1 genotypes were out of Hardy
      Weinberg equilibrium; this was largely due to K-ras mutated PDA cases. The
      Val/Val genotype was over five times more frequent in PDA cases with a K-ras
      mutation than in wild-type cases (OR = 5.25; P = 0.121). In PDA, polymorphisms in
      CYP1B1 might be related with K-ras activation pathways.

PMID- 18347982
TI  - Ethnicity and nonalcoholic fatty liver disease in an obesity clinic: the impact
      of triglycerides.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a growing problem that is associated
      with the metabolic syndrome. The goal of the present study was to evaluate for
      ethnic differences in NAFLD and clinical correlates of NAFLD. The study
      population consisted of 567 patients seen at an urban obesity clinic. Elevated
      aminotransferase levels were used as a surrogate marker for NAFLD. The prevalence
      of elevated aminotransferases was highest in Hispanics (39%), followed by
      Caucasians (28%), and African Americans (12%). In univariate analysis, elevated
      aminotransferase levels were associated with ethnicity (Hispanic > African
      American, P < 0.001, and Caucasian > African American P = 0.030),
      hypertriglyceridemia (P < 0.001), and male gender (P < 0.001). The pattern of
      results was confirmed in multivariate analysis, except that the differences
      between Caucasians and African Americans was no longer significant. In
      conclusion, in an obesity clinic population, elevated aminotransferase levels and
      hypertriglyceridemia were most common in Hispanics and least common in African
      Americans.

PMID- 18347983
TI  - Evaluation for tetanus antibodies in Korean-Americans living in the New York
      area: a pilot study.
AB  - Public health initiatives to immunize children and adults have effectively
      reduced the number of tetanus cases in the USA. However, in the third National
      Health and Nutrition Examination Survey (NHANES III), immigrants from Mexico had
      a 67% non-protective anti-tetanus antibody (ATA) level. Less work has been
      conducted among other immigrant populations to determine the extent of this
      observation. Objective To measure ATA levels among the Korean-American immigrant
      population. Methods A convenience sample of 50 Korean Americans born outside the
      USA was recruited to determine the levels of ATA. A non-protective level of ATA
      was defined as below 0.15 IU/ml. Results The mean age was 59.5 years and 82% were
      female. There were 43/50 (86% (95% confidence limits 76, 96)) patients with a non
      protective ATA level. Those between the ages of 50-59 years (94% were
      seronegative) and 60 years-highest age (92% were seronegative) were among the
      least likely to be protected. Neither gender nor a self-reported history of past
      tetanus immunization or military service predicted protection to tetanus.
      Discussion In this pilot study we found that 86% of Korean immigrants did not
      have protective ATA levels, with patients in the 50-59 year age range as unlikely
      to be protected as the older subjects. Patient reported history was unreliable in
      determining whether an individual had protective levels. Conclusion The vast
      majority of sampled Korean American immigrants lack protective ATA levels and are
      in need of immunization. Additional study is needed to determine the risk of
      other immigrant groups to tetanus.

PMID- 18347984
TI  - A mathematical model to predict CO2 removal in hollow fiber membrane oxygenators.
AB  - A mathematical model has been developed to predict CO(2) removal in hollow fiber
      membrane oxygenators. The model is analogous to one developed previously for
      predicting O(2) transfer. A mass transfer correlation was determined in water for
      O(2) and CO(2) exchange and collapsed onto one universal curve. The correlation
      was used to predict CO(2) removal in blood by incorporating a 'facilitated
      diffusivity' to account for the transport of CO(2) present as bicarbonate. The
      diffusion of bicarbonate greatly increased the ability of the oxygenator to
      remove CO(2) in blood compared to water. A fiber bundle module was fabricated to
      test the model predictions. The fiber bundle had a length of 13 cm and a bundle
      thickness of 0.2 cm. The module was tested in bovine blood at flowrates of 0.75,
      1.5, and 2.2 L/min and CO(2) removal rate predictions were within 9% of
      experimental measurements at all flowrates. The O(2) transfer rate predictions
      were within 10% of experimental measurements. A second module was manufactured
      with a bundle of length 4 cm and thickness of 1 cm. The CO(2) removal predictions
      were within the standard deviation of the experimental measurements.

PMID- 18347985
TI  - A new four-electrode Focused Impedance Measurement (FIM) system for physiological
      study.
AB  - A recently developed Focused Impedance Measurement (FIM) system (by the authors'
      group) uses six electrodes to localize a zone of interest. Because of 3D
      sensitivity it could give physiological information on large organs like stomach,
      lungs, etc. using surface electrodes in the frontal plane. This paper presents a
      modified FIM technique using four electrodes placed at the corners of a square
      matrix. Firstly current is driven through an adjacent electrode pair while the
      potential is measured across the opposite pair from which an impedance value is
      obtained. Then a similar measurement is made at 90 degrees to the above by
      changing connections to the electrode pairs appropriately. The sum of these two
      impedance values has a dominant contribution from the central region within the
      square matrix, giving the desired focusing. Experimental sensitivity maps
      obtained from a 2D phantom have verified the focusing effect. Compared to the
      previous six-electrode FIM system the focusing effect is slightly less, but this
      new technique has less negative artifacts in the periphery. This new FIM method
      can be applied both in the frontal plane and in the transverse plane of the human
      thorax, giving a further advantage besides requiring fewer electrodes.

PMID- 18347986
TI  - Bisindolylmaleimide IX facilitates extrinsic and initiates intrinsic apoptosis in
      TNF-alpha-resistant human colon adenocarcinoma COLO 205 cells.
AB  - Human COLO 205 colon adenocarcinoma cells are immune to extrinsic apoptosis
      induced by immunomodulatory cytokines. Among the antiapoptotic mechanisms
      responsible for the immune escape, the overexpression of the cFLIP protein seems
      to be critical. cFLIP appears to inhibit the TNF-alpha-induced death receptor
      signal. The application of the metabolic inhibitor bisindolylmaleimide IX (Bis
      IX), known as a potent PKC repressor, sensitized COLO 205 cells to TNF-alpha
      mediated apoptosis. The Western-blot analysis revealed that the susceptibility of
      human COLO 205 cells to apoptogenic stimuli resulted from time-dependent
      reduction in cFLIP(L) and TRADD protein levels. At the same time, the level of
      FADD protein was up-regulated. Additionally, the combined TNF-alpha and Bis-IX
      treatment caused cleavages of Bid and procaspase-9, as well as cytochrome c
      release. Thus, the evidence of this study indicates that Bis-IX facilitates the
      death receptor signal mediated by TNF-R1. Moreover, Bis-IX alone initiated
      intrinsic apoptosis, which could be abolished by Bcl-2 delivery. It heralds the
      involvement of mitochondria in caspase-8-independent intrinsic apoptosis. In
      turn, the treatment with bisindolylmaleimide III (Bis-III) did not assist TNF
      alpha-dependent apoptosis.

PMID- 18347987
TI  - Tumor-associated protein SPIK/TATI suppresses serine protease dependent cell
      apoptosis.
AB  - Serine protease dependent cell apoptosis (SPDCA) is a recently described caspase
      independent innate apoptotic pathway. It differs from the traditional caspase
      dependent apoptotic pathway in that serine proteases, not caspases, are critical
      to the apoptotic process. The mechanism of SPDCA is still unclear and further
      investigation is needed to determine any role it may play in maintaining cellular
      homeostasis and development of disease. The current knowledge about this pathway
      is limited only to the inhibitory effects of some serine protease inhibitors.
      Synthetic agents such as pefabloc, AEBSF and TPCK can inhibit this apoptotic
      process in cultured cells. There is little known, however, about biologically
      active agents available in the cell which can inhibit SPDCA. Here, we show that
      over-expression of a cellular protein called serine protease inhibitor Kazal
      (SPIK/TATI/PSTI) results in a significant decrease in cell susceptibility to
      SPDCA, suggesting that SPIK is an apoptosis inhibitor suppressing this pathway of
      apoptosis. Previous work has associated SPIK and cancer development, indicating
      that this finding will help to open the doorway for further study on the
      mechanism of SPDCA and the role it may play in cancer development.

PMID- 18347988
TI  - Wnt-expressing rat embryonic fibroblasts suppress Apo2L/TRAIL-induced apoptosis
      of human leukemia cells.
AB  - Wnt signaling enhances cell proliferation and the maintenance of hematopoietic
      cells. In contrast, cytotoxic ligand Apo2L/TRAIL induces the apoptosis of various
      transformed cells. We observed that co-culture of human pre-B leukemia cells KM3
      and REH with Wnt1- or Wnt3a-producing rat embryonic fibroblasts efficiently
      suppressed Apo2L/TRAIL-induced apoptosis of the lymphoid cells. This suppression
      occurs at the early stages of the Apo2L/TRAIL apoptotic cascade and,
      interestingly, the activation of the Wnt pathway alone in human leukemia cells is
      not sufficient for their full anti-apoptotic protection. We hypothesize that a
      stimulus emanating specifically from Wnt1- or Wnt3a-expressing rat fibroblasts is
      responsible for the observed resistance to Apo2L/TRAIL. This anti-apoptotic
      signaling was significantly hampered by the inhibition of the MEK1/ERK1/2 or
      NFkappaB pathways in KM3 and REH cells. Our results imply that paracrine Wnt
      related signals could be important for the survival of pre-B cell-derived
      malignancies.

PMID- 18347990
TI  - Attitudes of Australian heroin users to peer distribution of naloxone for heroin
      overdose: perspectives on intranasal administration.
AB  - Naloxone distribution to injecting drug users (IDUs) for peer administration is a
      suggested strategy to prevent fatal heroin overdose. The aim of this study was to
      explore attitudes of IDUs to administration of naloxone to others after heroin
      overdose, and preferences for method of administration. A sample of 99 IDUs
      (median age 35 years, 72% male) recruited from needle and syringe programs in
      Melbourne were administered a questionnaire. Data collected included
      demographics, attitudes to naloxone distribution, and preferences for method of
      administration. The primary study outcomes were attitudes of IDUs to use of
      naloxone for peer administration (categorized on a five-point scale ranging from
      "very good idea" to "very bad idea") and preferred mode of administration
      (intravenous, intramuscular, and intranasal). The majority of the sample reported
      positive attitudes toward naloxone distribution (good to very good idea: 89%) and
      92% said they were willing to participate in a related training program. Some
      participants raised concerns about peer administration including the competence
      of IDUs to administer naloxone in an emergency, victim response on wakening and
      legal implications. Most (74%) preferred intranasal administration in comparison
      to other administration methods (21%). There was no association with age, sex, or
      heroin practice. There appears to be strong support among Australian IDU for
      naloxone distribution to peers. Intranasal spray is the preferred route of
      administration.

PMID- 18347991
TI  - Homelessness and the response to emerging infectious disease outbreaks: lessons
      from SARS.
AB  - During the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, the
      potential introduction of SARS into the homeless population was a serious
      concern. Although no homeless individual in Toronto contracted SARS, the outbreak
      highlighted the need to develop an outbreak preparedness plan that accounts for
      unique issues related to homeless people. We conducted key informant interviews
      with homeless service providers and public health officials (n = 17) and
      identified challenges specific to the homeless population in the areas of
      communication, infection control, isolation and quarantine, and resource
      allocation. Planning for future outbreaks should take into account the need to
      (1) develop systems that enable rapid two-way communication between public health
      officials and homeless service providers, (2) ensure that homeless service
      providers have access to infection control supplies and staff training, (3)
      prepare for possible homeless shelter closures due to staff shortages or high
      attack rates among clients, and (4) plan for where and how clinically ill
      homeless individuals will be isolated and treated. The Toronto SARS experience
      provided insights that are relevant to response planning for future outbreaks in
      cities with substantial numbers of homeless individuals.

PMID- 18347989
TI  - Neuropsychological contributions to the early identification of Alzheimer's
      disease.
AB  - A wealth of evidence demonstrates that a prodromal period of Alzheimer's disease
      (AD) exists for some years prior to the appearance of significant cognitive and
      functional declines required for the clinical diagnosis. This prodromal period of
      decline is characterized by a number of different neuropsychological and brain
      changes, and reliable identification of individuals prior to the development of
      significant clinical symptoms remains a top priority of research. In this review
      we provide an overview of those neuropsychological changes. In particular, we
      examine specific domains of cognition that appear to be negatively affected
      during the prodromal period of AD, and we review newer analytic strategies
      designed to examine cognitive asymmetries or discrepancies between higher-order
      cognitive functions versus fundamental skills. Finally, we provide a critical
      examination of the clinical concept of Mild Cognitive Impairment and offer
      suggestions for an increased focus on the impact of cerebrovascular disease (CVD)
      and CVD risk during the prodromal period of AD.

PMID- 18347992
TI  - Demographic and behavioral factors associated with daily sugar-sweetened soda
      consumption in New York City adults.
AB  - The objective of the study was to assess the relations of socioeconomic and
      behavioral factors to frequent consumption of sugar-sweetened soda among New York
      City (NYC) adults and the relation of frequent consumption to body mass index
      (BMI; kg/m(2)). Data from the 2005 NYC Community Health Survey, a population
      based telephone survey, were analyzed. Frequent consumption was defined as
      drinking one or more 12-oz servings of sugar-sweetened soda on an average day;
      9,865 adults, aged 18 years and older, provided valid responses. Logistic
      regression was used to identify factors associated with frequent consumption, and
      linear regression models were used to assess the relation of frequent consumption
      to BMI. An estimated 27.5% of NYC adults are frequent sugar-sweetened soda
      consumers. Frequent consumption is independently associated with low household
      income (odds ratio [OR] = 1.7, 95% confidence interval [CI] 1.4-2.1 for <200% vs.
      > or =600% federal poverty level) and with ethnic group and nativity (e.g., OR =
      3.1, 95% CI 2.6-3.7 for U.S.-born blacks vs. whites). Men report more consumption
      then women, but an association of less education with frequent consumption is
      stronger among women. Adjusting for demographics, frequent consumption is
      associated with more television viewing and with less physical activity.
      Adjusting for demographics and behaviors, frequent consumption was associated
      with higher BMI among women (0.7 BMI units, 95% CI 0.1-1.2) but not among men.
      Disparities in sugar-sweetened soda consumption mirror obesity disparities.
      Improved surveillance and interventions are needed to better quantify and reduce
      consumption of sugar-sweetened beverages, especially in groups most impacted by
      obesity.

PMID- 18347993
TI  - Urban young women's experiences of discrimination and community violence and
      intimate partner violence.
AB  - This paper examines the interrelationships between urban young adult women's
      experiences of discrimination and community violence and their reports of
      involvement in intimate partner violence (IPV). We explore whether such
      experiences are independent risk factors for IPV victimization and perpetration,
      even when accounting for aggressive behaviors and related risk taking, including
      drinking and sexual initiation, during early adolescence. We use data from the
      Reach for Health study, in which a sample of 550 urban African American and
      Latina women was followed from recruitment in economically distressed middle
      schools into young adulthood, over approximately 7 years. At the last wave,
      respondents were 19-20 years old; 28% were raising children. More than 40%
      reported experiencing at least one form of racial/ethnic discrimination sometimes
      or often over the past year. About 75% heard guns being shot, saw someone being
      arrested, or witnessed drug deals within this time period; 66% had seen someone
      beaten up, 26% had seen someone get killed, and 40% knew someone who was killed.
      Concurrent reports of lifetime IPV were also high: about a third reported being a
      victim of physical violence; a similar proportion reported perpetration. Results
      of multivariate regression analyses indicate that discrimination is significantly
      associated with physical and emotional IPV victimization and perpetration,
      controlling for socio-demographic characteristics, including ethnic identity
      formation, and early adolescent risk behaviors. Community violence is correlated
      with victimization, but the relationship remains significant only for emotional
      IPV victimization once early behaviors are controlled. Implications for violence
      prevention are discussed, including the importance of addressing community
      health, as well as individual patterns of behavior, associated with multiple
      forms of violence victimization and perpetration.

PMID- 18347995
TI  - [Prevalence and evolution of delirium in a community population of 70 years and
      older].
AB  - INTRODUCTION: There are many studies on delirium in clinical populations and
      nursing home patients but not in community populations. This study has aimed to
      know the prevalence of delirium in a community population and to know the
      survival rate during a five-year period. METHOD: Case-control and survival study
      based on data from an epidemiological study to measure the prevalence and
      incidence of dementia in eight rural villages in Girona. According to the
      Diagnostic and Statistical Manual of Mental Disorders, delirium was identified
      for the prevalence study using the information obtained from the Cambridge Mental
      Disorders of the Elderly Examination. A hypothesis contrast method was used in
      order to compare all clinical features of the subjects according the presence or
      the absence of delirium. The Kaplan-Meier technique was used to estimate survival
      of the subjects, and a multivariate Cox regression analysis was done to know the
      effect of delirium on mortality over the five-year period. RESULTS: 1,460
      subjects older than 69 participated in the study. A prevalence of 0.96% (95%
      confidence interval [CI]: 0.43-1.49) was detected (14 cases of delirium). Mean
      survival for subjects with delirium was 3 years (CI 95%: 1.9-4.1) and it was
      slightly lower than for heal - thy controls. The presence of delirium increased
      the risk of death in five years by 2.65. CONCLUSION: The prevalence of delirium
      in community populations is low and most of the times it is superimposed on
      dementia. Patients with delirium have a higher risk of mortality at the end of a
      five-year period.

PMID- 18347996
TI  - [Diagnostic errors and temporal stability in bipolar disorder].
AB  - INTRODUCTION: The diagnosis of bipolar disorder is frequently modified during the
      course of the illness. MATERIAL AND METHODS: Diagnostic changes and associated
      errors are described for 1,153 patients diagnosed as bipolar disorder, aged over
      18 years and with at least ten follow-up visits. Data was extracted from a
      clinical registry of out-patient care specialized in Psychiatry and psychiatric
      hospitalizations of 25,152 patients representative of an urban area of 240,000
      inhabitants. Limit for diagnostic stability was established as the maintenance of
      the bipolar disorder diagnosis in at least 75% of the visits. RESULTS: A total of
      158 (46.1 %) out of 342 patients diagnosed as having a bipolar disorders in the
      first visit kept this diagnostic constant in subsequent evaluations.
      Infradiagnostic initial error was committed with 108 stable patients who were not
      diagnosed in the first visit. 184 patients diagnosed in the first visit with
      bipolar disorder had less than 75 % concordant diagnosis along the follow-up and
      could be considered as initial overdiagnosis. Two hundred and nine out of the 443
      patients who were diagnosed as bipolar disorder in their last visit did not keep
      stability criteria in their follow-up and could be considered therefore as final
      overdiagnosis. Thirty two stable patients not diagnosed in their last visit could
      be considered as infradiagnosis final error. Diagnosis from schizophrenia
      spectrum (F2) appears in one of every four psychiatric visits of the patients
      included in this study. Overlap was seen in three other categories: anxiety
      disorders (F4), personality disorders (F6) and substance abuse disorders.
      CONCLUSION: Initial course of bipolar disorder causes difficulties in the
      diagnosis.

PMID- 18347997
TI  - Pesticides, soft tissue sarcoma and non-Hodgkin lymphoma.

PMID- 18347998
TI  - Pesticides, soft-tissue sarcoma and non-Hodgkin lymphoma--historical aspects on
      the precautionary principle in cancer prevention.
AB  - BACKGROUND: After the 2(nd) World War a long range of chemical agents have been
      introduced on the market, both in Sweden and most other countries. From the
      1950's several pesticides gained increasing use in agriculture and forestry. In
      the 1970's public concern increased in Sweden especially regarding use of phenoxy
      herbicides to combat deciduous wood, although statements from different
      authorities were reassuring of the safety. MATERIALS AND METHODS: At the end of
      the 1970's the author and his colleagues published the first scientific evidence
      of an association between exposure to phenoxyacetic acids, chlorophenols and
      certain malignant tumours, i.e., soft-tissue sarcoma and malignant lymphoma. The
      study subjects were also exposed to contaminating dioxins such as 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD). Later studies showed also an association
      between certain persistent organic pollutants such as polychlorinated biphenyls
      and non-Hodgkin lymphoma (NHL) with an interaction with titers of antibodies to
      Epstein-Barr virus early antigen. These results have been corroborated in other
      studies. DISCUSSION: Over the years industry and its allied experts have attacked
      our studies, but in 1997 IARC classified TCDD as a human carcinogen, Group I. The
      increasing incidence of NHL in Sweden levelled off about 1990. The author
      postulated that the regulation or ban of the use of chlorophenols, certain
      phenoxy herbicides and some persistent organic pollutants in Sweden back in the
      1970s has contributed to the now decreasing incidence of NHL. Unfounded criticism
      from industry experts may prohibit the precautionary principle and early warnings
      of cancer risk can be ignored. Cancer risks by certain chlorinated phenols may
      serve as a model of how the precautionary principle should be used by taking
      early warnings seriously.

PMID- 18347999
TI  - Different etiological role of Helicobacter pylori (Hp) infection in
      carcinogenesis between differentiated and undifferentiated gastric cancers: a
      nested case-control study using IgG titer against Hp surface antigen.
AB  - BACKGROUND: The present study epidemiologically clarified the different roles of
      Helicobacter pylori (Hp) infection in carcinogenesis between two major
      histological types of noncardia gastric cancer (ncGC), intestinal
      (=differentiated) and diffuse (=undifferentiated), by analyzing IgG antibody
      titer against Hp surface antigen on the data set of a nested case-control study
      in a large cohort study conducted in Japan. METHODS: A total of 36,745 subjects
      aged 40 to 69 years in the Japan Health Center-based prospective study who
      responded to the baseline questionnaire and provided blood were followed over 15
      years; 350 ncGC cases (differentiated=242, undifferentiated=108) matched to
      controls were used. Using baseline blood samples, plasma IgG titer was measured
      using ELISA. The level of IgG titer >10 U (cut-off value) was classified into
      three grades in groups of equal number: low, middle, and high. RESULTS: IgG titer
      of Hp was significantly (p<0.01) higher in undifferentiated cases than in
      differentiated ones. Among the three grades of Hp IgG titer, the high titer was
      more closely associated with risk of undifferentiated ncGC (odds ratio (OR) for
      high=7.8, 95% confidence interval (CI)=2.4-24.9 vs. OR for low=6.4, 95% CI=2.1
      19.6), while the low titer was a better predictor of differentiated ncGC (OR for
      high=3.2, 95% CI=1.6-6.4 vs. OR for low=5.9, 95% CI=3.0-11.6, trend p < 0.05).
      The high titer group had the lowest risk to develop differentiated ncGC with <7
      years (OR=3.2, 95% CI=1.3-7.7), whereas the high titer group demonstrated the
      highest risk for undifferentiated ncGC developing (OR=11.6 95% CI=2.3-59.1).
      CONCLUSION: Our study epidemiologically confirmed that atrophic changes caused by
      Hp infection determine the development of differentiated-type ncGC, and the
      inflammation itself induced by Hp infection promotes the development of
      undifferentiated-type ncGC.

PMID- 18348000
TI  - Cancer risk by education in Iceland; a census-based cohort study.
AB  - Earlier studies have shown that cancer risk is related to educational level in
      many countries. The relationship between education and cancer risk has not been
      studied in the small, but ethnically homogenous, Icelandic population postulated
      to be outstanding as regards social equity. MATERIAL AND METHODS: We conducted a
      follow-up study of a cohort of 60,194 males and 58,505 females aged 20-64 at
      census 1981 in Iceland. Information on education from the census was classified
      into three educational groups and linked with the population-based Icelandic
      Cancer Registry. Standardized incidence ratios (SIRs) were calculated for the
      period 1982 to 2004. RESULTS: We found a significant association between
      educational level and cancer risk. Among males with academic education, the SIR
      was elevated for prostate cancer (SIR=1.17, 95% CI 1.05-1.30) and melanoma
      (SIR=1.41, 95% CI 1.00-1.93) and lowered for cancers of the lung (SIR=0.72, 95%
      CI 0.59-0.87) and stomach (SIR=0.67, 95% CI 0.48-0.90). Women with academic
      education had an increased risk of breast cancer (SIR=1.19, 95% CI 1.07-1.33) and
      a decreased risk of lung cancer (SIR=0.49, 95% CI 0.36-0.65). Increasing
      educational level was associated with a lowered risk of cervical cancer (p
      trend=0.017). DISCUSSION: The association between education and cancer incidence
      seen in this study resembles observations from other countries and probably
      reflects concordance between social status and certain risk factors for cancer.
      Our study confirms health-related socioeconomic differences in Iceland and must
      be taken into account when programmes for health promotion are planned.

PMID- 18348001
TI  - Estimated risk for secondary cancer in the contra-lateral breast following
      radiation therapy of breast cancer.
AB  - PURPOSE: To facilitate a discussion about the impact of dose heterogeneity on the
      risk for secondary contralateral breast (CB) cancer predicted with linear and non
      linear models associated with primary breast irradiation. METHODS AND MATERIALS:
      Dose volume statistics of the CB calculated for eight patients using a collapsed
      cone algorithm were used to predict the excess relative risk (ERR) for cancer
      induction in CB. Both linear and non-linear models were employed. A sensitivity
      analysis demonstrating the impact of different parameter values on calculated ERR
      for the eight patients was also included in this study. RESULTS: A
      proportionality assumption was established to make the calculations with a linear
      and non-linear model comparable. ERR of secondary cancer predicted by the linear
      model varied considerably between the patients, while the predicted ERR for the
      same patients using the non-linear model showed very small variation. The
      predicted ERRs by the two models were indistinguishable for small doses, i.e.
      below approximately 3 Gy. The sensitivity analysis showed that the quadratic
      component of the radiation-induction pre-malignant cell term is negligible for
      lower dose level. The ERR is highly sensitive to the value of alpha(1) and
      alpha(2). CONCLUSIONS: Optimization of breast cancer radiation therapy, where
      also the risk for radiation induced secondary malignancies in the contralateral
      breast is taken into account, requires robust and valid risk assessment. The
      linear dose-risk model does not account for the complexity in the mechanisms
      underlying the development of secondary malignancies following exposure to
      radiation; this is particularly important when estimating risk associated with
      highly heterogeneous dose distributions as is the case in the contralateral
      breast of women receiving breast cancer irradiation.

PMID- 18348002
TI  - Long-term results of a phase II trial of high-dose radiotherapy (60 Gy) and UFT/l
      leucovorin in patients with non-resectable locally advanced rectal cancer (LARC).
AB  - BACKGROUND: Preoperative radiochemotherapy is a cornerstone in patients with non-
      resectable locally advanced rectal cancer (LARC). To improve outcome (number of
      R0 resections and survival) high-dose radiotherapy (RT) was combined with oral
      UFT/l-leucovorin to allow tumour regression before radical intended surgery.
      METHODS: Pelvic RT was delivered with megavoltage photons using a 5 field
      technique. RT was CT-based, given 5 days a week through one posterior field and
      two lateral fields (48.6 Gy/27 fractions) to encompass the primary tumour and the
      regional lymph nodes. In addition, the tumour bed received a concurrent boost
      (5.4 Gy/27 fractions) and a final boost (6 Gy/3 fractions); thus GTV received 60
      Gy/30 fractions. Concurrent with RT patients received a daily dose of oral UFT
      300 mg/m(2) plus l-leucovorin 22.5 mg 5/7 days (divided in three doses). RESULTS:
      From September 2000 to November 2004, 52 patients (median age 60 years (32-83);
      median PS 0 (0-2)) with LARC (36 primary, 16 recurrent) were included in this
      phase II study. All but three patients received the planned 60 Gy, median
      duration of RT was 42 days (25-49). Toxicity was very modest; only four patients
      had a dose reduction of UFT. No hematological toxicity of clinical significance
      was seen. Non-hematological toxicity grade 1 (GI-toxicity, fatigue and/or
      dysuria) was frequently observed but only four patients experienced grade 3
      toxicity (diarrhoea and/or nausea/vomiting). Forty patients (77%) were operated
      (30 R0, 5 R1, 5 R2) median 55 days (27-112) after completion of RT. Seven (13%)
      patients had a pathological complete response (pCR). Thirty-one patients (60%)
      died after median 25.4 months (1.6-45.2 months). Twenty-one patients (40%) are
      still alive June 2007. CONCLUSIONS: Preoperative high-dose RT and concomitant UFT
      produces major regression in most patients with non-resectable LARC and thus a
      good chance of cure.

PMID- 18348003
TI  - Results of concomitant chemoradiation for cervical cancer using high dose rate
      intracavitary brachytherapy: study of JROSG (Japan Radiation Oncology Study
      Group).
AB  - The purpose of this study was to clarify outcome for concurrent chemoradiation
      (CT-RT) in locally advanced cervix cancer in Japan. This is a non-randomized
      retrospective analysis of 226 patients treated with definitive CT-RT or
      radiotherapy alone (RT alone) in nine institutions between 2001 and 2003.
      External irradiation consisted of whole pelvic irradiation and pelvic side wall
      boost irradiation, using a central shield during the latter half of the treatment
      with the anteroposterior parallel opposing technique. The external beam
      irradiation was performed with 1.8 or 2 Gy per fraction. High-dose-rate
      intracavitary brachytherapy (HDR) was performed in all cases. In chemotherapy,
      platinum based drugs were used alone or in combination with other drugs such as
      5FU. Grade of late complications was scaled retrospectively with CTCv2.0. Overall
      survival rate at 50 months of stage Ib, II and III, IV was 82% and 66% in CR-RT
      and 81% and 43% in R alone, respectively. Disease-free survival rate at 50 months
      of stage Ib, II and III, IV was 74% and 59% in CR-RT and 76% and 52% in R alone,
      respectively. There was no significant difference between CT-RT and RT for
      overall survival and disease free survival. Univariate analysis suggested that
      loco-regional control was better with CT-RT, but multivariate analysis could not
      confirm this finding. Compared to RT alone, CT-RT caused significantly more acute
      and late complications. Thus, late complication (grade 3-4) free survival rate at
      50 month was 69% for CT-RT and 86% for RT alone (p<0.01). The therapeutic window
      with concomitant radiochemotherapy and HDR brachytherapy may be narrow,
      necessitating a close control of dose volume parameters and adherence to systems
      for dose prescription.

PMID- 18348004
TI  - Concurrent mediastinal germ-cell tumour and haematological malignancy: case
      report and short review of literature.

PMID- 18348006
TI  - Physico-chemical and hygienic property modifications of stainless steel surfaces
      induced by conditioning with food and detergent.
AB  - The effect of repeated conditioning procedures (25 runs), consisting of soiling
      (milk and meat products) and cleaning steps, on the hygienic status, physico
      chemical properties and surface chemical composition of stainless steel (SS)
      surfaces, was investigated. Five SSs differing in grade and finish were used.
      Both soiling and surface cleaning/conditioning procedures resulted in a similar
      increase in the surface contamination with carbon, while the changes in the basic
      component of the surface free energy depended on the conditioning procedure. The
      passive film was also affected, the Fe/Cr ratio in particular. The hygienic
      status was also changed, especially with milk as shown by monitoring the number
      of residual adhering Bacillus cereus spores after contaminating the surface with
      spores followed by cleaning. The results show that in food environments, the
      presence and the nature of conditioning molecules play a major role in the
      hygienic status of SS surfaces.

PMID- 18348005
TI  - Childhood papillary thyroid cancer as second malignancy after successful
      treatment of rhabdomyosarcoma.

PMID- 18348007
TI  - Oxidative iron species and ocean challenges: a perspective.
AB  - The idea of using oxidative iron (Fe(6+)) to manage fouling and potentially
      invasive and pathogenic species in ballast water has merit and is attractive when
      viewed in the broadest context. Ferrate (Fe(6+)) has potential in ballast water
      management because it reduces a complex global problem to a single issue, viz.how
      to dispose of the waste which is predominantly Fe(3+). Waste iron disposal must
      be considered carefully because iron limits photosynthesis in oligotrophic
      oceans, alters physiological processes in bacteria and animals, produces reactive
      oxygen species, causes nitrosative stress and increased availability enhances the
      virulence of pathogenic bacteria. The case is made that the oxidative iron waste
      should be recycled rather than discharged into the ocean.

PMID- 18348008
TI  - Inhibition of barnacle (Amphibalanus amphitrite) cyprid settlement by means of
      localized, pulsed electric fields.
AB  - The increasing needs for environmental friendly antifouling coatings have led to
      investigation of new alternatives for replacing copper and TBT-based paints. In
      this study, results are presented from larval settlement assays of the barnacle
      Amphibalanus (= Balanus) amphitrite on planar, interdigitated electrodes (IDE),
      having 8 or 25 mum of inter-electrode spacing, upon the application of pulsed
      electric fields (PEF). Using pulses of 100 ms in duration, 200 Hz in frequency
      and 10 V in pulse amplitude, barnacle settlement below 5% was observed, while
      similar IDE surfaces without pulse application had an average of 40% settlement.
      The spacing between the electrodes did not affect cyprid settlement. Assays with
      lower PEF amplitudes did not show significant settlement inhibition. On the basis
      of the settlement assays, the calculated minimum energy requirement to inhibit
      barnacle settlement is 2.8 W h m(-2).

PMID- 18348009
TI  - Idiopathic intracranial hypertension--are we any closer to answers?

PMID- 18348012
TI  - Idiopathic intracranial hypertension: can studies of obesity provide the key to
      understanding pathogenesis?
AB  - The pathogenesis of idiopathic intracranial hypertension (IIH) is poorly
      understood. Several mechanisms have been suggested, but no one mechanism has been
      able to account for all manifestations of the disease. Although IIH predominantly
      affects obese, premenopausal women, little is known about whether or how the
      obesity contributes to the IIH. Obesity is a heterogeneous condition, consisting
      of different phenotypes that are influenced by the regional distribution of
      adipose tissue. This review explores the literature to integrate current
      knowledge on the relationships between obesity and IIH. The review evaluates the
      hypotheses that dysregulation of insulin, glucose metabolism, sex hormones,
      adipokines, glucocorticoids, lipids and free fatty acids in obesity could
      predispose to IIH. One potential common pathway linking metabolic disorders to
      the pathogenesis of IHH is a thrombotic tendency due to dysregulation of
      haemostatic risk factors. This could cause either occult cerebral sinus
      thrombosis or partial thrombosis of the parasagittal venous lacunae, with
      subsequent impaired resorption of cerebrospinal fluid and venous hypertension.
      Investigations that evaluate obesity, fat metabolism, endocrinological
      dysregulation and thrombotic tendency in patients with IIH are required so that
      pathogenic mechanisms can be clarified and management strategies in IIH can be
      improved.

PMID- 18348013
TI  - Adjacent segment disease after fusion for cervical spondylosis; myth or reality?
AB  - Cervical spondylosis is a common cause of radiculopathy and myelopathy, often
      treated by discectomy and interbody fusion. However, there has been a recent
      vogue for the use of artificial disc prostheses to decrease the risk of
      accelerated degenerative disease at adjacent levels. The short-term results of
      artificial disc replacements have been encouraging, but the long-term
      justification for using this new technology hinges on whether the incidence of
      adjacent segment disease decreases. It will also be necessary to demonstrate that
      movement at the operated levels is maintained and the incidence of device failure
      is low. We review the radiological, biomechanical and clinical evidence for
      adjacent segment disease, and the rationale for using artificial cervical disc
      replacements. There is presently insufficient evidence to justify the widespread
      use of artificial disc replacements in the treatment of cervical spondylosis, but
      neither is there sufficient evidence to criticize their use. Present evidence
      suggests that adjacent segment disease is partly due to the natural history of
      spondylotic disease and partly due to cervical fusion. Randomized trials are
      required to ascertain whether the incidence of adjacent segment disease changes
      with the use of artificial disc replacements in the long term. Indications for
      the use of artificial discs are presently unclear, but disc replacements might be
      recommended for 'young' patients who require an anterior cervical discectomy,
      with good ranges of neck movements, and an awareness of the satisfactory short
      term results, but lack of long-term outcome data, preferably within the limits of
      a clinical trial.

PMID- 18348014
TI  - In vitro models of neurotrauma.
AB  - Traumatic brain injury (TBI) continues to be an important cause of mortality and
      morbidity, but its pathophysiology is no longer considered an instantaneous
      irreversible event occurring at the time of injury. Therein, neuroprotection is
      the attempt to salvage sublethally injured neurons which subsequently die in post
      primary sequelae. Key to the discovery of neuroprotective strategies is the
      development of reliable models of brain injury--both in vivo and in vitro. While
      numerous studies on in vivo animal models have yielded encouraging results, these
      have largely failed to translate effectively in humans. One approach out of this
      impasse may be to re-explore in vitro models to dissect out specific
      pathophysiological mechanisms and only then test clearer hypotheses on in vivo
      models, which are more likely to subsequently translate into neuroprotective
      therapies of the future. Moreover, milder forms of TBI are a more realistic
      target for therapeutic intervention as more is understood about the vulnerability
      of surviving neurons and the capacity to salvage them. Several types of injury
      models are described including transection, compression, barotrauma,
      acceleration, hydrodynamic and cell stretch models with their advantages and
      disadvantages discussed in turn, as well as a survey of the cell cultures used,
      namely immortalized cell lines, primary cultures and organotypic (explant)
      cultures. We emphasize advances in three-dimensional strain simulation and a
      recent interest in modelling milder injuries, and argue that in vitro models may
      be a useful complement to in vivo models in studying TBI.

PMID- 18348015
TI  - Virtual neuroendoscopy: MRI-based three-dimensional visualization of the cranial
      nerves in the posterior cranial fossa.
AB  - This article presents the advances of three-dimensional (3D) virtual
      neuroendoscopy of the cranial nerves (CN) in the posterior fossa. Interactive 3D
      visualizations were generated and the anatomical landmarks, such as the root
      entry/exit zones (REZ) and cisternal segments of the CN were evaluated. Twenty
      patients (M:F, 6:14) with trigeminal neuralgia (TN) underwent MRI constructive
      interference in steady state (MRI(CISS)) imaging and subsequent 3D visualization
      based on explicit segmentation of the MRI(CISS) data and interactive evaluation
      with direct volume rendering including implicit segmentation. The 3D topography
      of the interesting CN V-X were evaluated with interactive and virtual
      neuroendoscopy. The anatomical landmarks of the CN V-X could be visualized in all
      20 cases (100%). The systematic application of virtual neuroendoscopy could be
      realized in all patients for the non-invasive observation of the CN without any
      technical difficulties. Interactive 3D visualization using explicit and implicit
      techniques for segmentation, and 3D direct volume rendering is demonstrated to
      successfully identify 3D neurovascular relations in patients with trigeminal
      neuralgia. It has the ability to provide a useful tool for surgeons in the pre-
      and intraoperative evaluation of such cases.

PMID- 18348016
TI  - Epidemiology of ventriculostomy in the United States from 1997 to 2001.
AB  - Ventriculostomy is a common practice in neurosurgery, but the annual trend of
      this procedure in the United States has not been reported in the literature. This
      study evaluates the annual trend during a recent 5-year period. Between 1997 and
      2001, a retrospective review was undertaken concerning all patients in the
      Nationwide Inpatient Sample (NIS) who had undergone ventriculostomy. The
      population sample represented approximately a 20% stratified sample of nonfederal
      hospitals in the United States. The annual number of patients who underwent
      ventriculostomy during the study period ranged from 20,586 to 25,634. Most
      patients were male (53.4%), with a mean age of 44.8 years, were commercially
      insured (46.0%) and had a median annual income above $25,000 (84.4%). Most
      frequent ICD-9-CM diagnoses were subarachnoid haemorrhage, intracerebral
      haemorrhage and obstructive hydrocephalus, respectively. The majority of
      ventriculostomies were performed in large, private, not-for-profit, metropolitan,
      teaching institutions. Mean length of hospital stay was 19.2 days. Regarding
      discharge status for patients who had undergone ventriculostomy, approximately
      one-quarter died in the hospital, one-third were discharged home and one-third
      were transferred to another institution. No demographic variables changed during
      the study with the exception of location of ventriculostomy in a teaching
      hospital, which increased from 64.4% in 1997 to 77.4% in 2001. Patient and
      hospital demographic characteristics were consistent during the study period. By
      extrapolation of the data, the prevalence of ventriculostomy in the United States
      averaged 24,380 per year. This study is the first to comprehensively document
      data concerning the epidemiology of this common procedure.

PMID- 18348017
TI  - Lumbar pressure and transcranial Doppler sonography in children with
      scaphocephaly.
AB  - The primary aim of this study was to assess whether there exists a relationship
      between lumbar cerebrospinal fluid (CSF) pressure and intracranial blood flow
      velocities as measured by transcranial Doppler sonography (TCD) in children with
      scaphocephaly. Another aim was to compare pre- and postoperative TCD. Using a
      transducer, lumbar CSF pressure (LP) was assessed in 21 children with
      scaphocephaly. TCD was performed, and the pulsatility index (PI) and the
      resistance index (RI) were obtained before and after cranioplasty. In 17 children
      LP was higher than the reference values. No significant differences were found in
      PI and RI indices before and after cranioplasty. LP values were significantly
      higher in children older than 6 months. There was no association between LP and
      PI and RI indices. In children with scaphocephaly a higher LP can be expected
      with age. Moreover, TCD is not a reliable tool in predicting abnormal LP values.

PMID- 18348018
TI  - Characteristics and surgical outcomes for medial temporal post-traumatic
      epilepsy.
AB  - A common post-traumatic location of epileptogenesis is the medial temporal lobe
      despite evidence of associated diffuse or remote cerebral injury. We undertook a
      review of post-traumatic medial temporal lobe epilepsy (MTLE) patients as part of
      an overall post-traumatic epilepsy population to assess the extent of cerebral
      injury sustained by this subpopulation and to establish whether surgical outcome
      differed from that of a non-traumatically-induced epilepsy population. A
      retrospective review of 57 patients operated for post-traumatic epilepsy (PTE)
      over a 10-year period (1993-2003) was undertaken with particular attention to
      those undergoing medial temporal resection. Preoperative magnetic resonance
      imaging (MRI) was assessed for the type and location of abnormalities.
      Postoperative outcomes were compared with those of patients with MTLE of non
      traumatic origin operated by the same surgeon. Of the 57 patients operated, 30
      cases underwent medial temporal lobe resection. The most common mechanism of
      injury was blunt trauma attributable to motor vehicle accidents with imaging
      abnormalities characterized by medial temporal sclerosis (MTS; 16 cases),
      T2/FLAIR hyperintensities (nine cases), periventricular gliosis (seven cases),
      diffuse cerebral atrophy (five cases) and focal encephalomalacia (three cases).
      Six patients had normal MRI studies. No significant differences in postoperative
      outcomes were found between post- and non-traumatic MTLE epilepsy groups. The
      presence of histopathological change in the medial temporal lobe varied greatly
      and provided no indication of a favourable postoperative outcome. Patients with
      post-traumatic medial temporal lobe epilepsy respond favourably to surgical
      treatment. In the case of medial temporal sclerosis, there is substantial
      variation of histopathological findings which correlate poorly with current
      imaging applications. The favourable outcomes obtained following surgery in this
      group attest to a commonality with other risk factors in the genesis of epilepsy
      in this location.

PMID- 18348019
TI  - Prognostic factors of postoperative visual outcomes in tuberculum sellae
      meningioma.
AB  - Tuberculum sellae meningiomas usually present optic pathway related symptoms,
      such as decreased visual acuity and/or visual field defect. In this report, the
      authors retrospectively analysed 27 patients with tuberculum sellae meningioma
      who underwent surgical treatment and then sought to identify prognostic factors
      of the postoperative visual outcomes. From April 1998 to June 2006, the authors
      treated 27 patients diagnosed with tuberculum sellae meningioma. Age, gender,
      duration of symptoms, tumour size, tumour consistency on intraoperative and T2WI
      findings, and resectability were analysed as potential prognostic factors of
      postoperative visual outcomes. Pre- and postoperative ophthalmological
      examinations were performed in all patients. Of the 27 patients who presented
      with visual dysfunction before operation, 12 were improved (44.4%), nine were
      unchanged (33.3%) and six worsened (22.2%). Those patients with a symptom
      duration of less than 1 year had a greater likelihood of visual improvement than
      those with a symptom duration of more than 1 year and those with a soft tumour
      had a greater likelihood of visual improvement than those with a hard tumour,
      though this was without statistical significance. Moreover, patients with high
      signal intensity lesion on T2-weighted images had a greater likelihood of visual
      improvement than those with an iso or low signal intensity with statistical
      significance. An excellent correlation was found between tumour consistency and
      appearance on T2-weighted images (p = 0.001). The results of this study indicate
      that MRI-T2WI can be used to estimate tumour hardness preoperatively and that
      this is an important prognostic factor of the visual impairments caused by
      intrasellar meningioma.

PMID- 18348020
TI  - Posterior approach vertebrectomy in the thoracolumbar spine with expandable cage
      reconstruction: indications and techniques based on eight cases.
AB  - We present a series of eight patients undergoing circumferential neural
      decompression and stabilization of the thoracolumbar spine via a single midline
      posterior approach, with complete vertebrectomy for a variety of indications.
      Four had primary tumours, two secondary tumours, one patient had tuberculosis and
      one had delayed deformity due to trauma. This single posterior approach is made
      possible via the use of an expandable cage that may be expanded in situ to offer
      anterior and middle column reconstruction. There were no major neurological
      complications and all patients with deficits improved postoperatively. Extensive
      posterior fixation was avoided with five patients undergoing a one above/one
      below fixation and three undergoing a two above/two below fixation. When combined
      with pedicle screw and rod fixation this anterior reconstruction makes a sound
      construct. The flexibility of this approach in the thoracolumbar spine, some of
      the biomechanical advantages and pitfalls are considered.

PMID- 18348021
TI  - Is total excision of spinal neurenteric cysts possible?
AB  - Spinal neurenteric cysts are intradural cystic lesions. These represent a part of
      the spectrum of developmental anomalies. These are rare lesions. Most of the data
      in literature is review of case reports. This made us evaluate our results of 23
      cases and review the literature. This is a retrospective study of 23 patients
      managed at our institute over 20 years. The slides were retrieved and
      histopathological features studied. Twenty patients were less than 30 years old
      and 21 were males. Follow-up was available for 21 patients with mean duration of
      71 months (range 2 months to 23 years). The typical presentation was backache
      with progressive neurological deficits pertaining to the level. Atypical
      presentations as acute onset, recurrent episodic events and aseptic meningitis
      were also noted. The cervicothoracic region was the most common site. 16 patients
      had cyst in intradural extramedullary plane and seven had intramedullary
      location. Associated vertebral anomalies as hemivertebrae, Klippel-Feil and spina
      bifida were noted in seven patients. There were two histological types of cysts
      with no correlation between the type of cysts and associated vertebral anomalies
      and extent of outcome. Partial excision though had higher risk of recurrence, was
      not associated with poorer outcome. Dorsal approach is an acceptable route with
      reasonably good results for this lesion. Spinal neurenteric cysts present at
      younger age with varied clinical presentations. These are commonly located
      intradurally ventral to the cord. Histological types have no effect on the
      outcome. Total excision is the choice of treatment. However, partial excision is
      a feasible option in intramedullary lesions and when significant adhesions occur.
      Although associated with higher risk of recurrence, the outcome is still good in
      these patients on re-excision.

PMID- 18348022
TI  - The safety and efficacy of vertebroplasty using Cortoss cement in a newly
      established vertebroplasty service.
AB  - Vertebroplasty provides an effective means of treating painful vertebral lesions
      although the majority of the literature relates to vertebroplasty using PMMA
      cement. The purpose of this study is to assess the safety and efficacy of
      vertebroplasty using Cortoss, a recently developed bis-GMA resin. Our newly
      established vertebroplasty service exclusively uses Cortoss cement and has a
      patient database which is updated on a regular basis using the medical records.
      To date, there are 34 patients on this database, mean age 66, in whom a
      vertebroplasty has been performed on 42 vertebral lesions with a mean of 2.2 ml
      of Cortoss injected into each lesion. The mean duration of follow up was 9.5
      months. Eighty-two per cent of patients reported an improvement in their
      symptoms, while 79% required less analgesia post vertebroplasty. A total of 88.2%
      experienced no significant complications. In 38% there was an asymptomatic
      leakage of Cortoss. Four patients (11.8%) experienced significant complications:
      one asymptomatic PE, one episode of transient radicular leg pain, one generalized
      rash and one patient suffered retropulsion of the Cortoss due to further
      vertebral malignancy. Cortoss vertebroplasty provides comparable efficacy and
      safety to the published literature for PMMA.

PMID- 18348023
TI  - Effects of fluid therapy following aneurysmal subarachnoid haemorrhage: a
      prospective clinical study.
AB  - Blood transfusions and intravenous fluids are commonly employed as rescue therapy
      for delayed cerebral ischaemia following aneurysmal subarachnoid haemorrhage
      (aSAH). We sought to determine effects of various fluid supplements on clinical
      outcome in patients following aSAH. Clinical events and laboratory data of 160
      aSAH patients were prospectively collected as part of 2 randomised controlled
      trials. Outcomes at discharge and at 6 months were measured with Glasgow Outcome
      Scale (GOS). Favourable outcome was defined as good recovery or moderate
      disability on GOS. All of the 160 patients received intravenous fluid supplements
      with crystalloids; 122 (76.3%) also received synthetic colloids (4% succinylated
      gelatine or 6% pentastarch). A higher daily dose of synthetic colloids for
      initial resuscitation seemed to be associated with more requirements for blood
      transfusions (p = 0.003) and occurrence of vasospasm in poor-grade patients (p =
      0.081), but blood transfusions themselves were not associated with occurrence of
      vasospasm. Compared with patients not receiving synthetic colloids, those
      receiving synthetic colloids had increased haemodilution, elevated inflammatory
      profiles, and decreased duration and strength of intact cerebral autoregulation.
      Multivariate analyses identified that blood transfusions (odds ratio, OR 3.38, p
      = 0.035) were associated with unfavourable outcome at discharge. Colloid fluids
      (OR 2.53/L/day, p = 0.025) promoted unfavourable outcome at 6 months (OR 4.45, p
      = 0.035), while crystalloids decreased unfavourable outcome (OR 0.27/L/day, p =
      0.005). Associations between synthetic colloids and crystalloids with GOS at 6
      months were dose-related. Intravenous fluid therapy using synthetic colloids or
      blood transfusions may be associated with increased unfavourable outcome
      following aSAH.

PMID- 18348024
TI  - Fibrinolytic therapy in spontaneous intraventricular haemorrhage: efficacy and
      safety of the treatment.
AB  - Intraventricular haemorrhage (IVH) is associated with a poor outcome. Simple
      external ventricular drainage has not modified the high morbidity and mortality
      of these patients. Our objective was to review our experience using
      intraventricular urokinase (UK) in treating patients with moderate to severe IVH.
      Prospective analysis of medical records of 14 patients diagnosed with spontaneous
      IVH who received ventriculostomy and intraventricular infusion of UK from January
      2002 to December 2005. Patients with the following characteristics were included:
      18-70 years of age, GCS between 5 and 14, and moderate to severe IVH (Graeb > or
      = 6) without simultaneous intraparenchymal haematoma > 30 ml. The final results
      were compared to historic control group (14 patients) treated between January
      1999 to December 2001 with ventriculostomy alone. All 28 patients accomplished
      the inclusion criteria. Patient age, initial GCS and Graeb classification of IVH
      were similar in the two groups of treatment. There was higher ventriculostomy
      obstruction rate in the non-UK group (33.3 vs. 0%; p > 0.05), a higher rate of
      intracranial hypertension in the non-UK group (66.6 vs. 16.6%; p = 0.036) and a
      lower mortality rate in the UK group (25 vs. 58.3%, p > 0.05). There was no
      rebleeding associated with UK treatment. Intraventricular UK appears to be a safe
      treatment. It is effective in the prevention of catheter blockage, speeding the
      clearance of IVH, and it is associated with lower rate of intracranial
      hypertension and death.

PMID- 18348025
TI  - Evaluation of POSSUM and P-POSSUM scoring systems for predicting the mortality in
      elective neurosurgical patients.
AB  - A simple way of evaluating surgical outcomes is to compare mortality and
      morbidity. Such comparisons may be misleading without a proper case mix. The
      POSSUM scoring system was developed to overcome this problem. The score can be
      used to derive predictive mortality and morbidity for surgical procedures. POSSUM
      and a modified version P-POSSUM have been evaluated in various groups of surgical
      patients for the accuracy of predicting mortality. These scoring systems have not
      been evaluated in neurosurgical patients. Thus, we tried to evaluate the
      usefulness of POSSUM and P-POSSUM scoring systems in neurosurgical patients in
      predicting in-hospital mortality. POSSUM physiological and operative variables
      were collected from all neurosurgical patients undergoing elective craniotomy,
      from April 2005 to Feb 2006. In-hospital mortality was obtained from the hospital
      mortality register. The physiological score, operative score, POSSUM predicted
      mortality rate and P-POSSUM predicted mortality rate were calculated using a
      calculator. The observed number of deaths was compared against the predicted
      deaths. A total of 285 patients with a mean age of 38 +/- 15 years were studied.
      Overall observed mortality was nine patients (3.16%). The mortality predicted by
      the P-POSSUM model was also nine patients (3.16%). Mortality predicted by POSSUM
      was poor with predicted deaths in 31 patients (11%). The difference between
      observed and predicted deaths at different risk levels was not significant with P
      POSSUM (p = 0.424) and was significantly different with POSSUM score (p < 0.001).
      P-POSSUM scoring system was highly accurate in predicting the overall mortality
      in neurosurgical patients. In contrast, POSSUM score was not useful for
      prediction of mortality.

PMID- 18348026
TI  - Number of burr holes as independent predictor of postoperative recurrence in
      chronic subdural haematoma.
AB  - Chronic subdural haematoma (cSDH) is one of the most frequent neurosurgical
      entities. Current treatment options include burr hole craniostomy, twist drill
      craniostomy or craniotomy. While burr hole craniostomy is the most often used
      technique, there are no studies analysing the use of one vs. two burr holes in
      respect to recurrence rates and complications. This retrospective study included
      76 (age: 60 +/- 12 years) patients presenting with cSDH admitted in our
      institution from January 2004 to December 2005. A total of 21 (27%) patients
      underwent bilateral craniostomy. The patients were assessed using the Markwalder
      Scale (2 +/- 0.71), Glasgow Coma Scale (14 +/- 1) and measuring the haematoma
      thickness (1.8 +/- 0.7 cm). The decision to perform one or two burr hole was made
      according to the personal preference of the treating neurosurgeon. All patients
      underwent irrigation and placement of closed-system drainage. Out of the 97
      haematoma, 63 (65%) haematomas were treated with two burr holes, whereas 34 (35%)
      were treated with one burr hole. Patients with one burr hole had a statistically
      significant (p < 0.05) higher recurrence rate (29 vs. 5%), longer average
      hospitalization length (11 vs. 9 days) and higher wound infection rate (9% vs.
      0%). A multivariate regression analysis identified the number of holes as single
      predictor for postoperative recurrence rate (r(2) = 0.12; p < 0.001). In this
      study, the treatment of cSDH with one burr hole only is associated with a
      significantly higher postoperative recurrence rate, longer hospitalization length
      and higher wound infection rate.

PMID- 18348027
TI  - An unusual presentation of thoracic cord compression by a dorsal arachnoid cyst
      in a 14-month-old boy. A discussion of the case and review of the literature.
AB  - Spinal arachnoid cysts are a rare cause of spinal cord compression in children
      and presenting symptoms may be subtle. We present a neurologically intact 14
      month-old boy who presented with pain and postural irritability from a thoracic
      arachnoid cyst.

PMID- 18348028
TI  - Primary amyloidoma of the thoracic spine causing paraparesis.
AB  - A 52-year-old lady presented with progressive paraparesis. MRI revealed collapse
      of D9 vertebrae which was infiltrated by a low signal lesion both on T1 and T2.
      She underwent vertebrectomy and insertion of moss cage. The histology came back
      as amyloidoma. The presentation, investigation and management of primary
      amyloidoma of the spine is discussed along with a review of the literature.

PMID- 18348029
TI  - Treatment of acute neurological deficit after cervical laminectomy with lumbar
      cerebrospinal fluid drainage.
AB  - Spinal cord ischaemia is a rare, but reported cause of acute deterioration
      following cervical laminectomies. Various adjuncts have been reported to protect
      against and treat cord ischaemia, including CSF diversion. We present a case of a
      patient who experienced an acute neurological deterioration following cervical
      laminectomies that improved following CSF drainage.

PMID- 18348030
TI  - Delayed diagnosis, due to the associated radiological abnormalities, of
      spontaneous intracranial hypotension caused by cerebrospinal fluid leakage at C1
      2.
AB  - Spontaneous intracranial hypotension (SIH) is an uncommon clinical entity that is
      often diagnosed after a delay, or it is misdiagnosed due to the variety of
      clinical presentations and the associated radiological findings. We present here
      a case of SIH associated with chronic subdural haematoma (SDH) and subarachnoid
      haemorrhage. Following the diagnosis of the SIH, the patient underwent injection
      of an epidural blood patch for the SIH and burr hole trephination was done for
      treating the chronic subdural haematoma.

PMID- 18348031
TI  - Post-traumatic pericallosal artery aneurysm presenting with subdural haematoma
      without subarachnoid haemorrhage.
AB  - A 27-year-old patient presented with severe headache and seizures about a month
      after the initial head trauma. Computed tomography (CT) brain scan revealed acute
      subdural bleed continuous into the interhemispheric region, with no subarachnoid
      haemorrhage. This was due to rupture of a traumatic pericallosal artery aneurysm.
      This represents a rare case of traumatic pericallosal artery aneurysm presenting
      with subdural haematoma without subarachnoid haemorrhage.

PMID- 18348032
TI  - Fatal cerebral ischaemia by embolization of a gunshot fragment from an
      extracranial penetrating injury.

PMID- 18348033
TI  - Dumbbell-shaped intrathoracic-extradural haemangioma of the thoracic spine.
AB  - Spinal haemangiomas are benign vasoproliferative lesions that are typically intra
      osseous and generally asymptomatic, although localized pain can be a symptom.
      Capillary and cavernous variants have been described. We describe a rare case of
      a dumbbell-shaped haemangioma of the thoracic spine with both an intraspinal
      extradural and intrathoracic component.

PMID- 18348034
TI  - Olfactory ensheathing cells in the nasal mucosa of the rat and human.
AB  - Olfactory ensheathing cells are unique glial cells which have the ability to
      encourage nerve fibres to grow, and may have potential for use as a therapy for
      spinal cord and brachial plexus injuries. These images show olfactory ensheathing
      cells in the olfactory mucosa of the nose, and provide insight into their
      function. The olfactory mucosa is likely to be a convenient source for these
      cells in future clinical studies of CNS repair.

PMID- 18348035
TI  - Dysphagia and hoarse voice: an unusual cause.
AB  - We report an unusual presentation and successful treatment of an extracranial
      skull base carotid aneurysm. The patient presented with a combination of multiple
      cranial nerve dysfunction and local mass effect. After endovascular treatment of
      this rare condition her symptoms resolved. The radiological images submitted
      demonstrate this rare condition well.

PMID- 18348037
TI  - Esters of 3-chloro-1,2-propanediol (3-MCPD) in vegetable oils: significance in
      the formation of 3-MCPD.
AB  - 3-Mono-chloropropane-1,2-diol (3-MCPD) is a contaminant that occurs in food in
      its free (diol) form as well as in an esterified (with fatty acids) form. Using a
      simple intestinal model, it was demonstrated that 3-MCPD monoesters and 3-MCPD
      diesters are accepted by intestinal lipase as substrates in vitro. Under the
      chosen conditions, the yield of 3-MCPD from a 3-MCPD monoester was greater than
      95% in approximately 1 min. Release from the diesters was slower, reaching about
      45, 65 and 95% of 3-MCPD after 1, 5 and 90 min of incubation, respectively.
      However, in human, the hydrolysis of 3-MCPD esters is unlikely to release 100% as
      3-MCPD, as triglycerides and phospholipids are hydrolysed in the intestine
      liberating 2-monoglycerides. Assuming a similar metabolism for 3-MCPD esters as
      that known for acylglycerols in humans in vivo, the de-esterification in
      positions 1 and 3 would thus be favoured by pancreatic lipases. Therefore, 3
      MCPD, and 3-MCPD-2 monoesters would be released, respectively, from the 1-/3
      monoesters, and the diesters potentially present in food. Hence, information on
      the exact amounts of the partial fatty acid chloroesters, i.e. 3-MCPD mono- and
      diesters, is important to assess the contribution of foods to the bioavailability
      of 3-MCPD. Therefore, a rapid method for the determination of the ratio of 3-MCPD
      monoesters to diesters in fats and oils was developed using gas chromatography
      mass spectrometry (GC-MS) and isotopically labelled 3-MCPD esters as internal
      standards. The analysis of 11 different samples of fat mixes typically employed
      in food manufacturing demonstrated that a maximum of about 15% of the total
      amount of 3-MCPD bound in esters is present in the monoesterified form. The
      potentially slower release of 3-MCPD from 3-MCPD diesters, and the mono- to
      diesters ratio suggest that 3-MCPD esters may in fact contribute only marginally
      to the overall dietary exposure to 3-MCPD. Further work on the bioavailability,
      metabolism and possible toxicity of chloroesters per se is warranted.

PMID- 18348038
TI  - Improved method for the determination of benzene in soft drinks at sub-ppb
      levels.
AB  - An automated, simple, and reproducible method based on isotope dilution headspace
      gas chromatography/mass spectrometry developed previously for the determination
      of benzene in soft drinks was further improved by adding sodium sulfate to
      samples, lowering the gas chromatography oven starting temperature to narrow
      benzene peak width, and increasing sample injection volume. This improved method
      had a lower detection limit (0.016 microg l(-1)) and good repeatability, and was
      used in a follow-up survey to assess benzene levels in 139 samples of soft drink
      products. Benzene was detected in 67% of the 139 products tested. Compared with
      the previous survey, the average benzene concentrations in most products from
      this survey were lower, and only a few products had benzene at elevated levels.

PMID- 18348039
TI  - Pattern of ivermectin (sheep) and doramectin (cattle) residues in muscular tissue
      from various anatomical locations.
AB  - This trial reports comparative drug residual concentrations in muscular tissue
      obtained from various anatomical locations after subcutaneous administration of
      ivermectin (IVM) to sheep and topical treatment with doramectin (DRM) to calves
      at recommended therapeutic dose rates. Seven muscle samples from different
      anatomical locations (rhomboideus, supraspinatus, semitendinosus, gluteus medius,
      longissimus dorsi thoracis, intercostales and diaphragma) were collected at
      several post-treatment sampling times. Samples were frozen at-20 degrees C until
      analyzed by HPLC. The highest IVM residual concentrations in muscular tissue from
      the different locations were found at 15 days post-treatment in sheep. Although
      the highest IVM mean concentrations were measured at 15 (16.8 +/- 5.17 ng g(-1))
      and 20 (10.5 +/- 4.06 ng g(-1)) days post-administration in the intercostales
      muscles, at 30 days post-administration, the IVM concentration in this location
      was similar to that measured in the rhomboideus and diaphragma muscles. DRM
      residual concentrations were quantified in muscular tissue from all anatomical
      locations after topical administration to calves. Maximum residue level was
      observed at 10 days post-treatment in all anatomical sites. The diaphragma muscle
      showed the highest DRM residue levels at 2 (22.0 +/- 4.35 ng g(-1)), 5 (45.2 +/-
      3.78 ng g(-1)) and 10 (57.9 +/- 9.57 ng g(-1)) days post-treatment in calves.
      These results demonstrated that the pattern of residue depletion from muscular
      tissue may differ according to its anatomical locations and/or physiological
      role. This should be considered in implementing residue control strategies in
      meat safety assurance for human consumption.

PMID- 18348040
TI  - Development of a lateral flow immunoassay strip for screening of
      sulfamonomethoxine residues.
AB  - A rapid lateral flow immunoassay screening method has been developed for the
      determination of sulfamonomethoxine (SMM) residues in swine urine. For this
      purpose, a specific monoclonal antibody (mAb), SMM4B9 for SMM, was generated and
      characterized. The mAb showed low cross-reactivity (not larger than 0.3%) to
      other sulfonamides and other potentially occurring analytes. Based on the
      competitive immunoassay principle, the strip was developed with the mAb SMM4B9
      and applied to the screening of SMM residues. The test strip is made up of a
      sample pad, a gold-conjugate SMM4B9 reagent pad, a blotted test membrane
      containing a test line, a control line (a nitrocellulose membrane spotted with
      SMM-BSA and goat anti-mouse antibody, respectively), and an absorbent pad. The
      test could be accomplished within 8-10 min. It was shown that the sensitivity of
      the test strip was as low as 5 ng ml(-1) of SMM and the half of maximal
      inhibition concentration (IC50) was calculated to be 10.78 +/- 0.22 ng ml(-1) by
      relative optical density. In unaided visual assessment the detection limit of the
      strip was 15 ng ml(-1). For samples spiked at 20 and 30 ng ml(-1) the coefficient
      of variation (CV (%)) was between 2.3 and 7.1%. When the test strip was compared
      with high-performance liquid chromatography (HPLC) analysis for naturally
      contaminated swine urine samples, the difference in results was less than 6.1%.
      The data suggest that the method has advantages of high sensitivity, specificity,
      simplicity and speed of performance, as well as the characteristics of
      repeatability, reproducibility or accuracy and assurance. Therefore, the test
      strip is suitable to determine SMM residues in swine urine rapidly and reliably
      by quantitative, semi-quantitative or qualitative detection.

PMID- 18348041
TI  - Optimal conditions for determination of zinc bacitracin, polymyxin B,
      oxytetracycline and sulfacetamide in animal feed by micellar electrokinetic
      capillary chromatography.
AB  - A separation technique for zinc bacitracin, polymyxin B, oxytetracycline and
      sulfacetamide in animal feedstuffs by micellar electrokinetic capillary
      chromatography (MEKC) was developed. The running buffer was 20 mmol l(-1) borate,
      20 mmol l(-1) phosphate, pH 8.4, containing 20 mmol l(-1) sodium dodecylsulphate
      and 10% (v/v) methanol. MEKC was performed at 25 degrees C; the applied voltage
      was 25 kV with a running pressure of 10 mbar. Simultaneous UV detection for all
      analytes was at 215 nm. The method was validated for specificity, accuracy,
      linearity, precision and robustness. It was shown to be specific, accurate
      (recoveries were 99.7 +/- 0.3, 99.9 +/- 0.9, 99.8 +/- 1.0 and 99.5 +/- 0.4,
      respectively, for oxytetracycline-, sulfacetamide-, polymyxin B- and zinc
      bacitracin-spiked samples of feed for cow, pigs, chicken and cattle), linear over
      the tested range (correlation coefficients > or =0.9987) and precise (RSDs below
      1.8% for each analyte). The method was applied to determine zinc bacitracin,
      polymyxin B, oxytetracycline and sulfacetamide as additives in animal feed.

PMID- 18348042
TI  - Determination of chloramphenicol in shrimp by liquid chromatography-electrospray
      ionization tandem mass spectrometry (LC-ESI-MS-MS).
AB  - A liquid chromatographic method with electrospray ionization tandem mass
      spectrometric (LC-ESI-MS-MS) detection and identification is described for the
      determination of chloramphenicol (CAP) in shrimp tissue. Homogenized shrimp
      samples were extracted by liquid-liquid extraction using ethyl acetate. d5
      Chloramphenicol (5D-CAP) was used as the internal standard. Data acquisition was
      in negative-ion multiple reaction monitoring (NMRM) mode using three transition
      reactions for CAP (m/z 321 --> 152, m/z 321 --> 257 and m/z 321 --> 194) and two
      for d5-chloramphenicol (m/z 326 --> 262 and m/z 326 --> 157). Method validation
      was carried out according to European Commission decision 2002/657/EC. The
      calibration curve was linear in the range 0.10-2.00 microg l(-1), with typical r2
      > 0.99. The decision limit (CC alpha) and detection capability (CC beta) were
      0.06 and 0.10 microg kg(-1), respectively. There was no influence of the matrix
      on the determination of chloramphenicol.

PMID- 18348043
TI  - Pesticide residues in grapes from vineyards included in integrated pest
      management in Slovenia.
AB  - Although the list of pesticides used in integrated pest management (IPM) in grape
      growing and their annual application rates are limited, we are still confronted
      with the problem of pesticide residues in grapes. This paper presents the results
      of pesticide monitoring of 47 samples of wine grapes (Vitis vinifera L.) from the
      2006 vintage from vineyards included in IPM. The grape samples were analysed for
      the presence of 67 pesticides. Among them 20 were allowed in IPM in 2006. Grapes
      were sampled at harvest. Two internal analytical methods were used for the
      determination of pesticides: gas chromatography-mass spectrometry (GC-MS) method
      for the determination of dithiocarbamates and a multi-residue GC-MS method. One
      grape sample (2.1%) contained no residues or they were below the limit of
      detection, 28 samples (59.6%) contained residues lower or equal than maximum
      residue levels (MRLs), and 18 samples (38.3%) exceeded national MRLs for
      cyprodinil (the concentration range was 0.03-0.40 mg kg(-1) of cyprodinil) and
      fludioxonil (concentration was 0.03 mg kg(-1) of fludioxonil). Multiple residues
      were found in 41 samples (87.2%). The highest number of pesticides detected per
      sample was seven. No violation of pesticides allowed in IPM was observed. Folpet
      (97.9%), cyprodinil (51.1%), dithiocarbamates (44.7%), chlorothalonil (23.4%),
      chlorpyriphos (19.1%) and pyrimethanil (14.9%) were the most frequently found
      pesticides in grapes. Risk assessment showed that the exceeded concentrations of
      cyprodinil and fludioxonil did not represent any risk for consumer's health (the
      national estimate of short-term intake as a percentage of the acceptable daily
      intake was below 100%).

PMID- 18348044
TI  - Novel approach to fast determination of multiple pesticide residues using ultra
      performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
AB  - A rapid, high-throughput method employing ultra-performance liquid chromatography
      with tandem quadrupole mass spectrometry (UPLC-MS/MS) was developed and optimized
      for simultaneous quantification and confirmation of 64 pesticide residues and
      their toxic metabolites in fruit extracts prepared by a buffered QuEChERS
      procedure. The total time required for UPLC-MS/MS analysis was 8 min plus 2 min
      for re-equilibration to the initial UPLC conditions. Performance characteristics
      were determined for apple extracts spiked at 10 microg kg(-1). The repeatability
      of measurements expressed as relative standard deviations was in the range 1.5
      13% at this level for most analytes. Thanks to very low limits of quantification
      (<10 microg kg(-1)for the majority of pesticides), an optimized method allows for
      the reliable control of not only common maximum residue limits (MRLs) set by
      European Union regulation for various pesticides/fruit combinations, but also of
      a uniform MRL of 10 microg kg(-1)endorsed for baby food.

PMID- 18348045
TI  - Dietary exposure to pesticide residues in Yaounde: the Cameroonian total diet
      study.
AB  - Dietary exposure to pesticide residues was assessed in Yaounde, Cameroon, using
      the total diet study (TDS) method. Sixty-three composite samples, representative
      of the foods as consumed in Yaounde, were collected, prepared, and analysed for
      residues of pesticides including organochlorine, organophosphorous, and
      pyrethroids. A multi-residue method was used with a limit of detection (LOD) of
      0.005 mg kg(-1). Additional analyses were performed for dithiocarbamates
      (LOD=0.050 mg kg(-1)), glyphosate (LOD=0.005 mg kg(-1)) and chlordecone
      (LOD=0.0008 mg kg(-1)) on certain composites samples. The overall contamination
      was low with 37 out of 46 pesticides below the LOD in all samples. The estimated
      upper bound (for values less than the LOD equal the LOD; and values less than the
      LOQ equal the LOQ) of the mean dietary exposures ranged from 0.24% (cypermethrin)
      to 3.03% (pirimiphos-methyl) of the acceptable daily intakes (ADIs) for
      pesticides for which at least one analysis was greater than the LOD. This study
      suggests a low dietary exposure to pesticide residues in Yaounde.

PMID- 18348046
TI  - LC-MS/MS multi-method for mycotoxins after single extraction, with validation
      data for peanut, pistachio, wheat, maize, cornflakes, raisins and figs.
AB  - Mycotoxin analysis is usually carried out by high performance liquid
      chromatography after immunoaffinity column cleanup or in enzyme-linked
      immunosorbent assay tests. These methods normally involve determination of single
      compounds only. EU legislation already exists for the aflatoxins, ochratoxin A
      and patulin in food, and legislation will come into force for deoxynivalenol,
      zearalenone and the fumonisins in 2007. To enforce the various legal limits, it
      would be preferable to determine all mycotoxins by routine analysis in different
      types of matrices in one single extract. This would also be advantageous for
      HACCP control purposes. For this reason, a multi-method was developed with which
      33 mycotoxins in various products could be analysed simultaneously. The
      mycotoxins were extracted with an acetonitrile/water mixture, diluted with water
      and then directly injected into a LC-MS/MS system. The mycotoxins were separated
      by reversed-phase HPLC and detected using an electrospray ionisation interface
      (ESI) and tandem MS, using MRM in the positive ion mode, to increase specificity
      for quality control. The following mycotoxins could be analysed in a single 30
      min run: Aflatoxins B1, B2, G1 and G2, ochratoxin A, deoxynivalenol, zearalenone,
      T-2 toxin, HT-2 toxin, alpha-zearalenol, alpha-zearalanol, beta-zearalanol,
      sterigmatocystin, cyclopiazonic acid, penicillic acid, fumonisins B1, B2 and B3,
      diacetoxyscirpenol, 3- and 15-acetyl-deoxynivalenol, zearalanone, ergotamin,
      ergocornin, ergocristin, alpha-ergocryptin, citrinin, roquefortin C, fusarenone
      X, nivalenol, mycophenolic acid, alternariol and alternariol monomethyl ether.
      The limit of quantification for the aflatoxins and ochratoxin A was 1.0 microg
      kg(-1) and for deoxynivalenol 50 microg kg(-1). The quantification limits for the
      other mycotoxins were in the range 10-200 microg kg(-1). The matrix effect and
      validation data are presented for between 13 and 24 mycotoxins in peanuts,
      pistachios, wheat, maize, cornflakes, raisins and figs. The method has been
      compared with the official EU method for the determination of aflatoxins in food
      and relevant FAPAS rounds. The multi-mycotoxin method has been proven by the
      detection of more than one mycotoxin in maize, buckwheat, figs and nuts. The LC
      MS/MS technique has also been applied to baby food, which is subject to lower
      limits for aflatoxin B1 and ochratoxin A, ergot alkaloids in naturally
      contaminated rye and freeze-dried silage samples.

PMID- 18348047
TI  - Odour investigation of granular polyolefins for flexible food packaging using a
      sensory panel and an electronic nose.
AB  - A study was carried out of the odour properties of polyolefins destined for
      flexible food packaging. A total of 25 homo- and copolymers of ethylene and five
      homo- and copolymers of polypropylene in pellet grade were analysed by a sensory
      panel. Principal component analyses of sensory data showed a perceptible and
      quantifiable difference between samples. Generally, polypropylene materials were
      judged less odorous than the majority of polyethylene pellets, especially the
      ethylene vinyl acetate copolymers. The feasibility of using a commercial
      electronic nose, equipped with 10 metal oxide semiconductors, to discriminate
      between the odour of plastic materials was also explored. Instrumental results
      were satisfactory and correlated well with panel answers, as shown by partial
      least-squares regression. Furthermore, application of a cluster analysis made it
      possible to differentiate polymer odours into strong, medium and weak.

PMID- 18348048
TI  - Migration of epoxidized soybean oil (ESBO) and phthalates from twist closures
      into food and enforcement of the overall migration limit.
AB  - Nineteen samples of food in glass jars with twist closures were collected by the
      national food inspectors at Danish food producers and a few importers, focusing
      on fatty food, such as vegetables in oil, herring in dressing or pickle, soft
      spreadable cheese, cream, dressings, peanut butter, sauces and infant food. The
      composition of the plasticizers in the gaskets was analysed by gas chromatography
      with flame ionization detection (GC-FID) and gas chromatography-mass spectrometry
      (GC-MS). Epoxidized soybean oil (ESBO) and phthalates were determined in the
      homogenized food samples. ESBO was the principal plasticizer in five of the
      gaskets; in 14 it was phthalates. ESBO was found in seven of the food samples at
      concentrations from 6 to 100 mg kg(-1). The highest levels (91-100 mg kg(-1))
      were in oily foods such as garlic, chilli or olives in oil. Phthalates, i.e. di
      iso-decylphthalate (DIDP) and di-iso-nonylphthalates (DINP), were found in seven
      samples at 6-173 mg kg(-1). The highest concentrations (99-173 mg kg(-1)) were in
      products of garlic and tomatoes in oil and in fatty food products such as sauce
      bearnaise and peanut butter. For five of the samples the overall migration from
      unused lids to the official fatty food simulant olive oil was determined and
      compared with the legal limit of 60 mg kg(-1). The results ranged from 76 to 519
      mg kg(-1) and as a consequence the products were withdrawn from the market.

PMID- 18348049
TI  - Assessing human exposure to phthalic acid and phthalate esters from mineral water
      stored in polyethylene terephthalate and glass bottles.
AB  - Phthalic acid and phthalate esters are of growing interest due to their
      significant usage and potential toxicity. Polyethylene terephthalate (PET) and
      glass are both widely used materials for bottled drinking water. In this study,
      phthalic acid (PhA), bis(2-ethylhexyl) phthalate (DEHP), dimethyl phthalate
      (DMP), diethyl phthalate (DEP), diisobutyl phthalate (DiisoBP) and dibutyl
      phthalate (DBP) were analysed in a large number of Italian bottled water samples.
      These samples showed different concentrations of phthalates are nearly 20 times
      higher in samples bottled in PET than those from glass bottles with total levels
      of phthalates of 3.52 and 0.19 microg l(-1), respectively. However, the observed
      levels do not represent a significant exposure pathway when considering the US
      Environmental Protection Agency (USEPA) reference dose (an estimate of a daily
      oral exposure to the human population, including sensitive subgroups, that is
      likely to be without an appreciable risk of deleterious effects during a
      lifetime). In addition, no significant correlation was found between the
      phthalate concentrations and the physicochemical properties of the different
      water samples, apart from the still/sparkling water parameter for the PET
      samples. In this instance, slightly higher concentrations were observed for the
      PET bottled still water samples than for the sparkling water samples, although no
      explanation has been found yet.

PMID- 18348050
TI  - Effect of microwaves on the migration of lithium and silicon from lithium
      disilicate (Li2O-2SiO2) glass.
AB  - Lithium disilicate (Li2O-2SiO2) glass was immersed in a static solution of
      deionized water and heated by a microwave or by conventional means for various
      times. The resulting Li+ and Si migration was compared by solution analysis and
      the corroded glass surfaces were compared by Fourier transform infrared
      reflection spectroscopy and scanning electron microscopy. Results show no
      substantial differences in migration or glass corrosion under the test conditions
      using 7.00 GHz microwave radiation, but leave open the possibility of very
      slightly altered kinetics using 5.86 GHz radiation. More testing at 2.45 GHz is
      suggested.

PMID- 18348051
TI  - An efficient semi-synthesis and structure revision of a cytotoxic triterpenoid 25
      acetoxy-3alpha-hydroxyolean-12-en-28-oic acid from Liquidamber styraciflua.
AB  - An efficient partial synthesis of 25-acetoxy-3alpha-hydroxyolean-12-en-28-oic
      acid (1), starting from oleanolic acid (2), has been developed in an efficient
      manner (13 steps, 21% yield), employing a photochemical reaction of nitrite 8 for
      the introduction of C-25 substituting group as the key step. Based on the
      comparison of its spectral data with those reported for compound 1 isolated from
      Liquidamber styraciflua, we found the structure in that paper was incorrectly
      assigned, and should be revised as 3alpha-acetoxy-25-hydroxyolean-12-en-28-oic
      acid (15).

PMID- 18348052
TI  - Two new sesquiterpenoids from the soft coral Sinularia polydactyla (Ehreberg).
AB  - Two new sesquiterpenoids, polydactins A (1) and B (2) and a known sesquiterpene,
      10alpha-hydroxycadin-4-en-15-al (3), were isolated from the soft coral Sinularia
      polydactyla (Ehreberg). Their structures were determined mainly by spectroscopic
      methods. Polydactin A (1) showed moderate cytotoxic activities against human oral
      epidermoid carcinoma cell lines (KB) and human breast carcinoma (MCF) tumour cell
      lines (in vitro).

PMID- 18348053
TI  - Artemisterol, a new steryl ester from the whole plant of Artemisia apiacea.
AB  - A new steryl ester, artemisterol (1), together with known compounds alpha-amyrin
      (2), beta-amyrin (3), beta-sitosterol (4), 5,6,7-trimethoxycoumarin (5), and 6
      methoxy-7,8-methylenedioxycoumarin (6), were isolated from the methanolic
      extracts of Artemisia apiacea by repeated column chromatography. The structure of
      1 was elucidated as stigmast-5-en-3beta,29-diol 29-p-hydroxycinnamate by spectral
      data analyses.

PMID- 18348054
TI  - Two new lignan glycosides from Trachelospermum lucidum (D. Don) Schum.
AB  - Two new lignans (1 and 2) having a diarylhydroxybutyrolactone skeleton were
      isolated from the leaves of Trachelospermum lucidum (D. Don) Schum. Their
      structures were elucidated to be apocynotrachelolegnin 5'-O-beta-d
      glucopyranoside (1) and rafanotrachelogenin 4-O-beta-d-glucopyranoside (2) on the
      basis of spectroscopic analysis. Two known lignans, matairesionoside-4-O-beta-d
      glucoside (3) and trachelosiaside (4), were also isolated from Trachelospermum
      lucidum.

PMID- 18348055
TI  - Two new lanostane triterpenoids from Poria cocos.
AB  - Two new lanostane triterpenoids, 29-hydroxypolyporenic acid C (4) and 25
      hydroxypachymic acid (5), together with three known compounds, ergosta-7,22-dien
      3beta-ol (1), polyporenic acid C (2) and pachymic acid (3), were isolated from
      the 95% ethanolic extract of the sclerotium of Poria cocos (Schw.) Wolf. Their
      structures were determined by extensive spectroscopic analyses, including IR, UV,
      ESITOF-MS, HRESI-MS, 1D and 2D NMR data (1H NMR, 13C NMR, 1H-1H COSY, NOESY, HSQC
      and HMBC).

PMID- 18348056
TI  - Benzophenone C-glucosides from Polygala glomerata Lour.
AB  - Four new benzophenone C-glucosides, glomeratides A (1), B (2), C (3), and D (4),
      along with a known compound arrilanin G (5), have been isolated from the whole
      plant of Polygala glomerata Lour. Their structures were determined by extensive
      analyses of their spectral data. Compounds 1-5 showed hepatoprotective activities
      against d-galactosamine-induced toxicity in WB-F344 rat hepatic epithelial stem
      like cells.

PMID- 18348057
TI  - A new lignan glycoside from the rhizomes of Imperata cylindrica.
AB  - A new lignan glycoside, 6-acetyl-1-[1,3-(4,4'-dihydroxy-3,3'-dimethoxy-beta
      truxinyl)-beta-d-fructofuranosyl]-alpha-d-glucopyranoside (1), named
      impecyloside, was isolated from the rhizomes of Imperata cylindrica. The
      structure of the compound was determined by spectroscopic data including FABMS,
      UV, IR, 1H NMR and 13C NMR (DEPT) and 2D NMR (COSY, HSQC, HMBC).

PMID- 18348058
TI  - A new thiaziedione from the fruits of Xanthium sibiricum.
AB  - A novel sulphur-containing compound named xanthiazinone (1) was isolated from the
      ethanolic extract of the fruits of Xanthium sibiricum, along with four known
      compounds, xanthiazone (2), xanthiside (3), xanthienopyran (4) and 5
      hydroxypyrrolidin-2-one (5). Their structures were determined on the basis of
      spectroscopic techniques.

PMID- 18348059
TI  - Pyrrolizidine alkaloids from Cynoglossum furcatum.
AB  - Two new pyrrolizidine alkaloids have been isolated from the roots of Cynoglossum
      furcatum. On the basis of chemical and spectroscopic evidence, structures of the
      compounds have been elucidated. They are lactodine (3), a monoster alkaloid and
      viridinatine (4), a pyrrolizidine diester alkaloid. The structure of lactodine is
      elucidated as 9-O-(-)lactyl heliotridine and viridinatine as 7-O-(-)viridifloryl
      echinatine.

PMID- 18348060
TI  - Stemoninine-type alkaloids from the roots of Stemona sessilifolia.
AB  - Two new stemoninine-type alkaloids, stemoninine A (1) and B (2), along with two
      known Stemona alkaloids, bisdehydrostemoninine (3) and bisdehydrostemoninine A
      (4), were isolated from the roots of Stemona sessilifolia, and their structures
      and relative configurations were determined on the basis of spectrometric data
      analysis.

PMID- 18348061
TI  - A new Diels-Alder type adduct and two new flavones from the stem bark of Morus
      yunanensis Koidz.
AB  - Fractionation of the ethanolic extract of the stem bark of Morus yunanensis
      resulted in the isolation of a new Diels-Alder type adduct and two new flavones,
      named yunanensin A (1), yunanensol A (2) and yunanensol B (3), respectively,
      together with a known flavone (4). Their structures were determined on the basis
      of spectroscopic analysis and chemical methods. Among them, compound 1 showed
      moderate antioxidant and significant cytotoxic activities, and compound 2 showed
      potent anti-inflammatory activity.

PMID- 18348062
TI  - A new sulphated nor-sesquiterpene from mangrove Laguncularia racemosa (L.)
      Gaertn. F.
AB  - A new sulphated nor-sesquiterpene, 3alpha-hydroxysulphonyloxy-5alpha,6alpha-epoxy
      megastigmen-9-one (1), and a known sulphated lipid, 5'-(hydroxysulphonyloxy)
      jasmonic acid (2), have been isolated from the twigs and leaves of mangrove
      Laguncularia racemosa (L.) Gaertn. F. The structure of the new compound was
      elucidated on the basis of detailed analysis of spectroscopic data and chemical
      reaction.

PMID- 18348063
TI  - The effect of puerarin on serum nitric oxide concentration and myocardial eNOS
      expression in rats with myocardial infarction.
AB  - Puerarin (1) is a major effective ingredient extracted from the traditional
      Chinese medicine Ge-gen (Radix Puerariae, RP). Recently, puerarin has been used
      to treat patients with coronary artery diseases (CAD). However, the mechanisms of
      puerarin on CAD are still not very clear. In this study, we investigated the role
      of puerarin on serum nitric oxide (NO) concentration, myocardial endothelial
      nitric oxide synthase (eNOS) gene expression, the protein expression of eNOS and
      inducible nitric oxide synthase (iNOS), as well as the level of protein kinase B
      (Akt/PKB) phosphorylation in rats with myocardial infarction. We found that
      puerarin (120 mg/kg/day, i.p.) could increase serum nitrite concentration in rat
      with myocardial ischemia (MI). It also induced the gene expression or activation
      of eNOS, protein expression of eNOS, and the Akt/PKB phosphorylation. From these
      results, we suggested that puerarin could increase serum nitric oxide level of
      rat with myocardial infarction, which should be one of the mechanisms of the
      therapeutic effect of puerarin on CAD. The increased expression of eNOS and the
      Akt/PKB pathway may be the underlying mechanism by which puerarin stimulates NO
      production.

PMID- 18348064
TI  - Abstracts from the 10th European Regional International Society for the Study of
      Xenobiotics Meeting.

PMID- 18348068
TI  - Humoral immune response against epidermal growth factor encapsulated in
      dehydration rehydration vesicles of different phospholipid composition.
AB  - We investigated the influence of dehydration-rehydration vesicles (DRV)
      phospholipid composition and the addition of other components on human
      recombinant epidermal growth factor (hrEGF) encapsulation efficiency and its
      release from liposomes. Encapsulation of EGF into DRV composed of
      phosphatidylcholine with different unsaturation levels was around 20-35%. The
      best result was obtained with dipalmitoyl phosphatidylcholine: cholesterol
      (DPPC:Ch) liposomes (35%) corresponding to the lowest hrEGF release during one
      month of storage. Even with this phospholipid composition, modification of the
      DRV procedure by including an extrusion step did not improve hrEGF encapsulation
      efficiency, rendering less stable particles. The inclusion of recombinant P64k
      from Neisseria meningitidis (rP64k), as such or conjugated to hrEGF, decreased
      the encapsulation efficiency of the latter protein into DRV or freeze and thaw
      multilamellar vesicles (FATMLV). The hrEGF release from liposomes could be
      related to the interaction between this polypeptide and the bilayer, as evidenced
      by increased carboxyfluorescein release from hrEGF-DRV; less susceptibility to
      fluorescence quenching by acrylamide in the presence of liposomes; and a
      measurable decrease of phospholipid phase transition Delta enthalpy (DeltaH). DRV
      comprising saturated phospholipids (DPPC:Ch or distearoyl phosphatidylcholine
      [DSPC]:Ch) and containing the conjugate EGF-P64k induced a more efficient immune
      response against hrEGF than unsaturated phospholipid and alum in terms of total
      IgG, IgG(2a), and IgG(2b) subclasses and the ability of antibody to inhibit the
      interaction of the EGF receptor with hrEGF.

PMID- 18348069
TI  - Liposome fluidity alters interactions between the ganglioside GM1 and cholera
      toxin B subunit.
AB  - Cholera toxin is a complex protein with a biologically active protein (A subunit)
      and a cell targeting portion (B subunit). The B subunit is responsible for
      specific cell binding and entry of the A subunit. One way to limit potential
      toxicity of the toxin after exposure is to introduce cellular decoys to bind the
      toxin before it can enter cells. In this study the ganglioside GM1, a natural
      ligand for cholera toxin, was incorporated into liposomes and the interaction
      between fluorescent B subunit and the liposome determined. Liposome membrane
      fluidity was determined to play a major role in the binding between liposomes and
      the cholera toxin B subunit. Liposomes with lower fluidity demonstrated greater
      binding with the B subunit. The findings from this study could have important
      implications on formulation strategies for liposome decoys of toxins.

PMID- 18348070
TI  - Physicochemical and safety evaluation of 5-aminolevulinic acid in novel liposomes
      as carrier for skin delivery.
AB  - In this study we successfully entrapped 5-aminolevulinic acid (ALA) in liposome,
      although it exists as a zwitter ion. A molar ratio of 2:1:2.5 phosphatidyle
      thanolamine (PE)/cholesterol/sodium stearate represented the best condition to
      achieve high entrapment efficiency (29.37 +/- 1.21%), and the average vehicle
      size was 133.6 +/- 2.8 nm. After 32 days of storage, the vehicle sizes of
      formulations with PE series were still approximately less than 200 nm. The safety
      of liposomes was tested and ensured both with regard to cellular cytotoxicity and
      erythrocyte hemolysis. Safety studies showed that liposome formulations did not
      affect cell viability except when both potassium stearate and sodium oleate were
      added. Moreover, PE and PE/cholesterol did not damage human erythrocytes in this
      study. The range of the hemolytic effect caused by liposomes was 5 to 37% and the
      effect was dependent on the amount of sodium stearate added to the formulation.
      According to the release rates and skin penetration of ALA liposomes in vitro,
      PE/cholesterol/sodium stearate liposomes might increase skin penetration, and it
      was shown that penetration across the stratum-corneum (sc) layer was the rate
      limiting process. Images from confocal laser scanning microscopy (CLSM) confirmed
      the great potency of liposomes for delivering ALA into skin.

PMID- 18348071
TI  - Utility of targeted glucocorticoids in cancer therapy.
AB  - Glucocorticoids can inhibit solid tumor growth via downregulation of tumor
      associated inflammation/angiogenesis. In this minireview we describe the possible
      mechanisms of glucocorticoid action in tumor growth inhibition. We also present
      an overview of the current status of tumor-targeted glucocorticoid delivery. It
      appears that long-circulating liposomes are the only targeting system currently
      being explored for this purpose.

PMID- 18348072
TI  - Physicochemical characterization and study of in vitro interactions of pH
      sensitive liposomes with the complement system.
AB  - Complement activation is an important step in the acceleration of liposome
      clearance. The anaphylatoxins released following complement activation may
      motivate a wide variety of physiologic changes. We performed physicochemical
      characterization and in vitro studies of the interaction of complement system
      with both noncirculating and long-circulating pH-sensitive and nonpH-sensitive
      liposomes. The liposomes were characterized by diameter, zeta potential, and
      atomic force microscopy (AFM). The study of liposome interactions with complement
      system was conducted using hemolytic assay in rat serum. All liposomes presented
      a similar mean diameter (between 99.8 and 124.3 nm). The zeta potential was
      negative in all liposome preparations, except in liposomes modified with
      aminopoly (ethyleneglycol) 2000-distearoylphosphatidylethanolamine (aPEG(2000)
      DSPE), which presented positive zeta potential. Atomic force microscopy images
      showed that non-long-circulating pH-sensitive liposomes are prone to vesicles
      aggregation. Non-pH-sensitive liposomes complement system activates, while pH
      sensitive liposomes showed to be poor complement activators in rat serum.

PMID- 18348073
TI  - Biosensor-based evaluation of liposomal behavior in the target binding process.
AB  - In this study we evaluated the quartz crystal microbalance (QCM) as a biosensor
      for a real-time investigation of liposomal binding, under dynamic flow
      conditions, onto target proteins immobilized at the sensor. The mass-sensitive
      frequency changes of quartz sensors allow for a quantification of the liposomal
      binding process. Furthermore, simultaneous damping analysis gives an insight into
      liposomal behavior, such as the degree of liposomal deformation or spreading at
      the target surface. In this study a series of liposomes was evaluated, differing
      in the kind and concentration of ligands interacting with appropriate target
      proteins. It became evident that an increase in homing device concentration
      accelerated deformation and flattening of liposomes, triggering a fusion process.
      Furthermore, liposomal deformation corresponded with the binding affinity of
      target molecules, comparing biotin/avidin with E-selectin/ligand interactions.
      Deformation could be emphasized using dioleoylphosphatidylethanolamine (DOPE) as
      a fusiogenic membrane component, while sterical stabilization by
      polyethylenglycol (PEG-PE) appeared in a low degree of deformation. Consequently,
      the online detection of liposomal target binding by QCM is an excellent facility
      to control and predict the liposomal behavior at the target site for increasing
      therapeutic potency.

PMID- 18348074
TI  - Liposomes as carriers for verbascoside: stability and skin permeation studies.
AB  - In this study the influence of liposomal incorporation on both the stability and
      the in vitro (trans) dermal delivery of verbascoside was evaluated. The effect of
      drug entrapment into vesicles on its radical scavenging activity was also
      studied. Liposomes were obtained from soy phosphatidylcholine and cholesterol
      according to the film hydration method. Stability of verbascoside-loaded vesicles
      was studied over 6 months. Results showed that verbascoside can be incorporated
      in liposomes (E% = 57-66%), preventing its degradation. Stability studies
      (dynamic lager light scattering [DLLS] measurements and transmission electron
      microscopy [TEM] visualization) pointed out that vesicles were stable for 90 days
      and neither verbascoside leakage nor vesicle size alteration occurred during this
      period. The effects of vesicular incorporation on verbascoside diffusion through
      skin were investigated in vitro using newborn pig skin. Results showed that
      liposomes promoted drug accumulation into the stratum corneum but they did not
      give rise to any significant transdermal verbascoside delivery. Finally, results
      obtained from a 1, 1-diphenyl-2-pierylhydrazyl (DPPH) radical assay demonstrated
      that liposomes did not interfere with the radical scavenging activity of
      verbascoside.

PMID- 18348075
TI  - Invisibility of tissues and the mother/fetus paradox: an hypothesis.
AB  - How do tissues hide themselves from the body's natural defense system? Anonymity
      is difficult to sustain in the blood stream. Almost all surfaces become tagged by
      polyionic molecules, such as proteins, within milliseconds of being exposed to
      plasma (which, after all, is an abundant source of animal glue). Both the tagging
      and the gluing are spontaneous events and result from the release of
      electrostatically bound water when ionic groups of the surface and the protein
      mutually satisfy their respective charges. The driving forces responsible for the
      spontaneity of the adsorption/gluing process are various attractive forces and
      the disordering of bound water leading to a gain in entropy. But suppose the
      surface of an intruder had no surface charges, causing it to resemble the surface
      of a slice of (bulk) water. The polyionic proteins would not find anything to
      tag, there is no entropy gain, there are no attractive interactions, and the
      interloper would be invisible.

PMID- 18348078
TI  - Human subject testing of leakage in a loose-fitting PAPR.
AB  - Leakage from loose-fitting PAPRs (powered air-purifying respirators) can
      compromise the safety of wearers. The Martindale Centurion MAX multifunction PAPR
      is a loose-fitting PAPR that also incorporates head, eye, and ear protection.
      This respirator is used in mines where coal dust usually is controlled by
      ventilation systems. Should the respirator be depended on for significant
      respiratory protection? Ten human volunteers were asked to wear the Centurion MAX
      inside a fog-filled chamber. Their inhalation flow rates were measured with small
      pitot-tube flowmeters held inside their mouths. They were video imaged while they
      breathed deeply, and the points at which the fog reached their mouths were
      determined. Results showed that an average of 1.1 L could be inhaled before
      contaminated air reached the mouth. As long as the blower purges contamination
      from inside the face piece during exhalation, the 1.1 L acts as a buffer against
      contaminants leaked due to overbreathing of blower flow rate.

PMID- 18348079
TI  - Enhanced protection against cytokine- and fatty acid-induced apoptosis in
      pancreatic beta cells by combined treatment with glucagon-like peptide-1 receptor
      agonists and insulin analogues.
AB  - We recently showed that insulin analogues exhibit a beta-cell protective
      function. The aim of this study was to test if the anti-apoptotic activity of GLP
      1 agonists and insulin analogues is mediated by different pathways and if
      combined treatment may provide augmented protection against beta-cell death.
      Incubation of INS-1 cells with cytokines or fatty acids increased the number of
      apoptotic cells and caspase 3 activity, which was reduced by pretreatment with
      GLP-1 and its receptor agonists exendin-4 and AVE0010 by 50-60%. Similar effects
      (about 40% reduction) were observed after pretreatment with several insulin
      analogues. Combined treatment revealed additive activity and resulted in
      prevention of both cytokine- and fatty acid-induced apoptosis by up to 80%. No
      acute Akt-phosphorylation in response to GLP-1 receptor agonists could be
      observed, however, it became detectable after 24-hour stimulation. Gene silencing
      of Akt2 increased cytokine-induced apoptosis 2-fold. Under these conditions the
      beta-cell protective activity of AVE0010 remained completely unaltered. We show
      here that the anti-apoptotic activity of GLP-1 and its receptor agonists AVE0010
      and exendin-4 is enhanced by addition of insulin analogues and that the anti
      apoptotic action of GLP-1 mimetics is mostly unrelated to Akt2 signaling. It is
      suggested that combination of GLP-1 receptor agonists and insulin analogues,
      specifically insulin glargine, may represent a new therapeutic option for
      preservation of beta-cell mass in type 2 diabetic patients.

PMID- 18348080
TI  - High omega-3 fat intake improves insulin sensitivity and reduces CRP and IL6, but
      does not affect other endocrine axes in healthy older adults.
AB  - Aging diminishes hormone secretion and target cell responsiveness, possibly due
      to loss of cell membrane fluidity or alteration of membrane phospholipids
      affecting signal transduction. We investigated whether a high omega-3
      polyunsaturated fatty acid diet would improve endocrine function in 6 men and 6
      women aged over 60 years. Subjects first ate an isocaloric control diet for 6
      weeks, followed by an 8-week experimental diet, which included 720 g of fatty
      fish weekly plus 15 ml of sardine oil daily. In the last week, we measured RBC
      membrane fatty acids on each diet, performed pituitary, adrenal, hepatic, and
      Leydig cell endocrine provocative testing, and assayed selected cytokines. We
      also assessed insulin sensitivity utilizing octreotide insulin suppression
      testing and assessed free fatty acid (FFA) responses to isoproteronol. Insulin
      sensitivity increased significantly after 8 weeks on the omega-3 diet and FFA
      responses trended lower. Serum C-reactive protein was significantly reduced and a
      trend towards lower IL-6 was noted. No differences were found in other metabolic
      parameters, adiponectin levels, or hormone responses. We conclude that, in older
      people, high omega-3 consumption increases insulin sensitivity, may reduce FFA
      mobilization by catecholamines, and reduces inflammatory markers, but did not
      alter endocrine responsiveness after 8 weeks.

PMID- 18348081
TI  - Chemotherapy with doxorubicin in progressive medullary and thyroid carcinoma of
      the follicular epithelium.
AB  - Twenty-two patients (mean age 61) with metastasizing, progressive, nonradioiodine
      accumulating thyroid carcinoma of the follicular epithelium were treated with
      doxorubicin between 2000 and 2005. Tumors were histologically classified as
      follicular in 15 patients (68%) and papillary in 7 patients (32%). In addition,
      nine patients (mean age 51 years) with medullary thyroid carcinoma were treated
      with doxorubicin between 1997 and 2005. Treatment consisted of doxorubicin:
      either 8 cycles of 15 mg/m2 weekly or 3 cycles of 60 mg/m2 every 3 weeks,
      repeated once, depending on response and side effects. The effect of therapy was
      evaluated by radiographic imaging, [18F] FDG-PET, and bone scans. In patients
      with papillary or follicular thyroid carcinoma, 5% had a partial regression over
      6 months, 42% had stable disease for a median of 7 months (range: 1-22), and 53%
      had continuous progression established over 5 months (range: 1-11). Three
      patients died before completing chemotherapy. In patients with medullary thyroid
      carcinoma, 11% had a partial regression over 6 months followed by stable disease
      for 3 months, 11% had stable disease over 7 months, and 79% demonstrated
      progressive disease established over 5 months (range: 2-12). Doxorubicin can be a
      valid chemotherapy option, especially for advanced or metastatic thyroid
      carcinoma of the follicular epithelium.

PMID- 18348082
TI  - Modulation of adipocytokines response and weight loss secondary to a hypocaloric
      diet in obese patients by -55CT polymorphism of UCP3 gene.
AB  - Decreased expression or function of UCP3 (uncoupling protein 3) could reduce
      energy expenditure and increase the storage of energy as fat. Some studies have
      pointed to a role of UCP3 in the regulation of whole body energy homeostasis,
      diet induced obesity, and regulation of lipids as metabolic substrates. The C/C
      genotype of a polymorphism in the UCP3 promoter (-55C-->T) is associated with an
      increased expression of UCP3 mRNA in muscle. The aim of our study was to
      investigate the influence of -55CT polymorphism of UCP3 gene on adipocytokines
      response and weight loss secondary to a hypocaloric diet in obese patients. A
      population of 107 obese (body mass index >30) nondiabetic outpatients was
      analyzed in a prospective way. Before and after three months of a hypocaloric
      diet, an indirect calorimetry, tetrapolar electrical bioimpedance, blood
      pressure, a serial assessment of nutritional intake with 3-day written food
      records, and biochemical analysis were performed. The lifestyle modification
      program consisted of a hypocaloric diet (1520 kcal, 52% of carbohydrates, 25% of
      lipids and 23% of proteins). The exercise program consisted of aerobic exercise
      for at least 3 times per week (60 minutes each). The mean age was 49.5+/-34.5
      years and the mean BMI 34.5+/-4.8, with 27 males (25.3%) and 80 females (74.7%).
      Ninety patients (25 males/65 females) (83.6%) had the genotype 55CC (wild group)
      and 17 patients (2 male/15 females) (16.4%) 55CT (mutant group). The percentage
      of responders (weight loss) was similar in both groups (wild group: 84.7% vs.
      mutant group: 81.8%). BMI, weight, fat mass, systolic blood pressure, LDL
      cholesterol, waist circumference, and waist-to-hip ratio decreased in the wild
      group and RMR and VO (2) were increased. In the mutant group, BMI and weight
      decreased. Leptin and IL-6 levels have a significant decrease in the wild group
      (9.6%: p<0.05) and (30.5%: p<0.05), respectively. Patients with -55CC genotype
      have a significant decrease in leptin, interleukin 6, BMI, weight, fat mass,
      systolic blood pressure, LDL cholesterol, waist circumference, waist-to-hip ratio
      weight, fat mass, and systolic blood pressure.

PMID- 18348083
TI  - Association of the 163A/G and 1181G/C osteoprotegerin polymorphism with bone
      mineral density.
AB  - The aim of the study was to investigate the distribution of 163 A/G
      osteoprotegerin gene promoter and 1181 G/C osteoprotegerin exon 1 polymorphisms
      in a group of women with different hormonal status and to analyze their
      relationship with BMD. Osteoprotegerin polymorphisms and BMD were analyzed in 332
      women (69 premenopausal and 263 postmenopausal). BMD was quantified at the lumbar
      spine (L 2-4), femoral neck, and total hip. Genotyping for the presence of
      different polymorphisms was performed using the Custom Taqman ((R)) SNP
      Genotyping assays. There were not significant differences in BMD according to 163
      A/G genotype. However, significant differences in lumbar spine BMD were found
      according to 1181 G/C alleles. Thus, women with CC genotype had significant
      higher BMD at the lumbar spine than those with GC or GG genotype. No differences
      were found in femoral neck and total hip BMD. In age-adjusted models, the 1181
      G/C OPG polymorphism explained 2.2% of BMD variance at the spine, 0.3% at the
      femoral neck, and 0.9% at the total hip in the whole group. In the subgroup of
      premenopausal women, the polymorphism was strongly related to spine BMD, and
      explained 11.5% of the variance, whereas body weight explained 7.9%. The 1181 G/C
      polymorphism was associated with lumbar spine BMD in Spanish women. Premenopausal
      women with the CC genotype had a higher BMD.

PMID- 18348084
TI  - A specialized cDNA microarray (Mouse Lipid Chip) reveals hepatic overexpression
      of serum amyloid a in high-fat diet-fed mice.

PMID- 18348085
TI  - Continuing education self-study program: Semantic memory and language processing
      in aphasia and dementia.

PMID- 18348086
TI  - Semantic memory and language processing in aphasia and dementia. Foreword.

PMID- 18348087
TI  - Semantic memory and language processing in aphasia and dementia. Preface.

PMID- 18348088
TI  - Semantic memory and language processing: a primer.
AB  - Semantic memory refers to our long-term knowledge of word and object meaning.
      There is increasing evidence that rather than being a passive warehouse of
      knowledge, semantic memory is a dynamic system whose effectiveness relies on the
      coordination of multiple components distributed across a large network of
      cortical regions. Damage to one or more of these components produces distinct
      profiles of impairment in aphasia and dementia. Furthermore, such differences are
      associated with different responses to behavioral treatment. That is, effective
      treatment for semantically based language disorders in aphasia may have very
      limited success in dementia. We argue that treatment specificity demands a
      comprehensive understanding of the structure of semantic memory and the nature of
      its compromise. Here, we review several neuroanatomically informed theories of
      semantic organization with respect to the effects of semantic impairment on
      language processing in aphasia and neurodegenerative disease.

PMID- 18348089
TI  - Effects of semantic impairment on language use in Alzheimer's disease.
AB  - Many studies present apparently conflicting results and conclusions about the
      effects of Alzheimer's disease (AD) on language use. This review attempts to
      reconcile these apparently conflicting results regarding the language impairments
      in AD by discussing how the slow deterioration of the semantic system at the
      feature level interacts with the task demands of tests used to evaluate
      performance. In particular, performance is impaired on tasks that require
      relatively complete, elaborate semantic representations but is preserved when the
      task requires only partial semantic representations consisting largely of shared
      features. The variety of language impairments reported in complex, multiword
      tasks are likely attributable to a combination of the deterioration of semantic
      representations and reduced working memory resources. The few available treatment
      studies for language impairments in AD suggest that treatments designed for
      adults with other language impairments, such as aphasia, may also be effective in
      AD.

PMID- 18348090
TI  - Effects of semantic impairment on language processing in semantic dementia.
AB  - Semantic dementia is a neurodegenerative disease characterized by progressive
      loss of conceptual and lexical knowledge. Cortical atrophy remains relatively
      isolated to anterior and inferior portions of the temporal lobe early in semantic
      dementia, later affecting more extensive regions of temporal cortex. Throughout
      much of the disease course, frontal and parietal lobe structures remain
      relatively intact. This distribution of cortical damage produces a unique
      language profile. Patients with semantic dementia typically experience profound
      deficits in language comprehension and production in the context of relatively
      well-preserved functioning in domains such as phonology, executive function,
      visuospatial processing, and speech perception. We discuss the effects of
      semantic impairment on language processing in semantic dementia within the
      context of an interactive theory of semantic cognition that assumes the active
      coordination of modality-neutral and modality-specific components. Finally, we
      argue the need for an etiology-specific language intervention for this
      population.

PMID- 18348091
TI  - In search of meaning: reading and writing in Alzheimer's disease.
AB  - Decline in semantic memory is a key feature of Alzheimer's disease, and reading
      and writing performance reflects this loss. The article presents an overview of
      theoretical reading and spelling models, including definitions of key terminology
      and controversies surrounding the interaction of semantics and the orthographic
      lexicon. We review literature supporting a direct lexical nonsemantic route in
      reading and writing. The reading and writing deficits of Alzheimer's disease are
      contrasted with those of semantic dementia. Methods of assessing semantic memory
      in reading and writing are outlined, including administering published tests,
      word lists, homophones, written confrontation naming, verbal fluency, and written
      narrative analysis.

PMID- 18348092
TI  - Treatment for anomia in semantic dementia.
AB  - Anomia is a striking and consistent clinical feature of semantic dementia (SD), a
      progressive aphasia syndrome associated with focal cortical atrophy of the
      anterior temporal lobes. Word retrieval deficits in patients with SD have been
      attributed to the loss of conceptual knowledge, resulting in an impairment
      referred to as semantic anomia. Whereas an abundance of research has been
      dedicated to treatment for anomia in individuals with focal brain damage due to
      stroke, considerably less work has been done regarding treatment for patients
      with progressive language decline. The purpose of this article is to review the
      available literature concerning the nature and treatment of anomia in individuals
      with SD. Several studies have shown that new lexical learning remains possible in
      these patients. However, newly learned information is likely to be constrained by
      the learning context, and increased reliance on perceptual and autobiographical
      contextual information may be necessary to provide critical support for new
      vocabulary acquisition. There is also evidence suggesting that treatment may slow
      the progression of anomia over time, even affording some protective benefit to
      lexical items that are not yet lost. However, treatment efforts are likely to be
      most beneficial at early stages of the disease, when residual semantic knowledge
      as well as relatively spared episodic memory may support new learning.

PMID- 18348093
TI  - Evaluating the effectiveness of semantic-based treatment for naming deficits in
      aphasia: what works?
AB  - This article reviews the basic principles and evidence for the effectiveness of a
      semantic-based treatment for naming deficits in aphasia. This article focuses on
      three aspects of semantic-based treatment. First, the theoretical basis for
      semantic treatment approaches to alleviate naming deficits is explained. Second,
      the different types of semantic treatment approaches (i.e., substitutive and
      restitutive treatments) are reviewed. More attention is provided to restitutive
      treatment approaches, and some ideas regarding why these treatments may be
      effective are discussed. We argue that strengthening access to impaired semantic
      and phonologic representations and facilitating generalization to untrained but
      related targets are two factors determining the success of a restitutive-based
      semantic treatment. Finally, in the third section of the article, the effect of
      semantic treatment on the overall communicative effectiveness and suggestions for
      future research in this field are discussed.

PMID- 18348094
TI  - [Hospitals failing minimum volumes in 2004: reasons and consequences].
AB  - BACKGROUND: In 2004 Germany introduced annual minimum volumes nationwide on five
      surgical procedures: kidney, liver, stem cell transplantation, complex
      oesophageal, and pancreatic interventions. Hospitals that fail to reach the
      minimum volumes are no longer allowed to perform the respective procedures unless
      they raise one of eight legally accepted exceptions. The goal of our study was to
      investigate how many hospitals fell short of the minimum volumes in 2004, whether
      and how this was justified, and whether hospitals that failed the requirements
      experienced any consequences. METHOD: We analysed data on meeting the minimum
      volume requirements in 2004 that all German hospitals were obliged to publish as
      part of their biannual structured quality reports. We performed telephone
      interviews: a) with all hospitals not achieving the minimum volumes for complex
      oesophageal, and pancreatic interventions, and b) with the national umbrella
      organisations of all German sickness funds. RESULTS: In 2004, one quarter of all
      German acute care hospitals (N=485) performed 23,128 procedures where minimum
      volumes applied. 197 hospitals (41%) did not meet at least one of the minimum
      volumes. These hospitals performed N=715 procedures (3.1%) where the minimum
      volumes were not met. In 43% of these cases the hospitals raised legally accepted
      exceptions. In 33% of the cases the hospitals argued using reasons that were not
      legally acknowledged. 69% of those hospitals that failed to achieve the minimum
      volumes for complex oesophageal and pancreatic interventions did not experience
      any consequences from the sickness funds. However, one third of those hospitals
      reported that the sickness funds addressed the issue and partially announced
      consequences for the future. The sickness funds' umbrella organisations stated
      that there were only sparse activities related to the minimum volumes and that
      neither uniform registrations nor uniform proceedings in case of infringements of
      the standards had been agreed upon. DISCUSSION: In spite of the high number of
      hospitals that failed to achieve the minimum volumes in 2004, only few hospitals
      experienced consequences from the sickness funds. The reluctance of the payers
      may be explained, amongst others, by the small number of patients affected and
      the percentage of cases where legally accepted exceptions applied. In view of the
      partly unclear definitions of the exceptions and difficulties in the
      interpretation and execution of the minimum volumes in the hospitals and at the
      sickness fund level, it may be helpful to formulate more concrete instructions
      for the implementation of the standards.

PMID- 18348095
TI  - [Integration of hospital social services in the rehabilitation of accident
      patients by the statutory accident insurance. Results of a one-year model
      project].
AB  - In accident patient care, there is a substantial overlap between the scope of
      duties of hospital social services and tasks fulfilled by the German statutory
      accident insurances' visiting staff that regularly takes care of accident
      patients. Therefore, a project on the integration of hospital social services
      into the organizational structures of the German statutory accident insurance was
      initiated which aimed at optimising communication and realising synergy effects.
      A formative evaluation of the project was conducted that provided process- and
      outcome-related data for a comprehensive evaluation of the strengths and
      potentials of the project. Report forms containing patient-related information
      were completed by hospital social services. Forms were evaluated in terms of
      their utility for case management by accident insurance administrators using a
      checklist. Project implementation and procedures were documented and evaluated
      using semi-structured interviews with social services staff and accident
      insurance employees. Through the model, a comprehensive care for accident
      patients could be reached. In one third of all cases reviewed, rehabilitation
      management could be improved by including hospital social services. Moreover, in
      one third of all cases, care-related activities initiated by accident insurance
      funds could be reduced by involving local hospital social services. The report
      form used by hospital social services was evaluated as a useful tool in the
      context of patient care and rehabilitation management. The model was evaluated by
      interview participants as a highly targeted approach in accident patients' care
      management. Implications of the study for improving health care are discussed.

PMID- 18348096
TI  - [Impact of demographic changes on health care expenditure in Germany: an analysis
      considering the expenditures of decedents].
AB  - The purpose of this study was to evaluate the impact of demographic changes on
      future health care expenditure of the German social health insurances considering
      the expenditures of survivors and decedents by age. The study analysed data from
      269,646 members up to the age of 99 years of the AOK - one of Germany's largest
      social health insurers - in the State of Hesse in 2000/2001. In order to
      determine future health care expenditures, per-capita expenditures by age for
      outpatient, inpatient, rehabilitation, and nursing services of survivors and
      decedents (death within the next 12 months) were multiplied by the estimated
      number of survivors and decedents by age in Germany in 2020, 2035 und 2050.
      Expenditures for all ages were summed together. The paper shows that demographic
      changes until 2050 will lead to an increase of health care expenditures by 20% in
      total or less than 1% annually. Considering the future re-duction in workforce,
      demographic changes until 2050 will result in an estimated increase in health
      care expenditures per employee by about 57% (undifferentiated model). Considering
      the cost of survivors and decedents separately, this increase will amount to 50%.
      Hence, undifferentiated models overestimate the impact of demographic changes by
      about 10%.

PMID- 18348097
TI  - [Psychic symptoms and mental health service utilisation--an epidemiologic study
      in the city of Stuttgart].
AB  - A newly developed questionnaire has been administered to the children and their
      parents during the medical examination of the school doctors of the local board
      of public health. The 40-item questionnaire asks for sociodemographic data (age,
      gender, nationality, brothers and sisters), height, weight, psychic symptoms for
      the prevalence period of the last seven days and the last month, alcohol,
      nicotine and drug abuse, medication, eating behavior and delinquency. The
      questionnaire for parents additionally asks if the child has been in
      psychotherapy during the last twelve months and if parents think that there are
      enough treatment facilities that are easily available. As it takes only about
      five to eight minutes to answer the questionnaire the acceptance has been very
      good. 481 pupils from eleven primary schools in ten sections of the city of
      Stuttgart (Germany) could be included. Answering the questionnaire could quite
      easily be integrated in the medical examinations of the school doctors of the
      local board of public health. The most common complaints of the pupils for the
      last seven days were feelings of inner restlessness (24.0%), difficulties in
      falling asleep (22.5%), headaches (20.8%), stomachaches or cramps (19.6%) and
      nervousness (18.5%). Alcohol and nicotine abuse were not relevant in this age
      group. The treatment rate during the last 12 months has been 4.4% and the
      utilisation of mental health services has been considered by 4.2% of the parents
      during this period. Only 25.8% of non-German parents think that the care
      provision is sufficient. The substantial unfulfilled mental health needs of the
      pupils should have consequences for service planning.

PMID- 18348098
TI  - [Air quality in schools - classroom levels of carbon dioxide (CO2), volatile
      organic compounds (VOC), aldehydes, endotoxins and cat allergen].
AB  - Children are assumed to be more vulnerable to health hazards and spend a large
      part of their time in schools. To assess the exposure situation in this
      microenvironment, we evaluated the indoor air quality in winter 2004/5 in 92
      classrooms, and in 75 classrooms in summer 2005 in south Bavaria, Germany. Indoor
      air climate parameters (temperature, relative humidity), carbon dioxide (CO2) and
      various volatile organic compounds, aldehydes and ketones were measured.
      Additionally, cat allergen (Fel d1) and endotoxin (LAL-test) were analysed in the
      settled dust of school rooms. Data on room and building characteristics were
      collected by use of a standardised form. Only data collected during teaching
      hours were considered in analysis. The median indoor CO2 concentration in the
      classrooms ranged in the winter and summer period from 598 to 4 172 ppm and 480
      to 1 875 ppm, respectively. While during the winter period in 92% of the
      classrooms the CO2 daily medians went above 1 000 ppm, the percentage of
      classrooms with increased CO2 concentration fell to 28% in summer. In winter, in
      60% of classes the daily median CO2 concentration exceeded 1 500 ppm, while in
      summer this threshold was reached by only 9%. A high concentration of CO2 was
      associated with a high number of pupils, a low room surface area and a low room
      volume. The levels of total volatile organic compounds (TVOC) in classrooms
      ranged between 110 and 1 000 microg/m3 (median in winter 345 microg/m3, in summer
      260 microg/m3). Acetone, formaldehyde and acetaldehyde were measured in
      concentrations from 14.0 to 911 microg/m3, from 3.1 to 46.1 microg/m3, and from
      2.9 to 78 microg/m3, respectively. The other aldehydes were detected in minor
      amounts only. The median Fel d1 level in winter was 485 ng/g dust (20 to 45 160
      ng/g) and in summer it was 417 ng/g (40-7 470 ng/g). We observed no marked
      differences between the two sampling periods and between smooth floors and rooms
      with carpeted floors. No differences were found according to room surface area
      and room volume. The median endotoxin contents in winter and summer were 19.7
      EU/mg dust (6.6 to 154 EU/mg) and 32.2 EU/mg (9.6 to 219 EU/mg), respectively.
      The levels varied significantly between the sampling periods, but were
      independent of room surface area, room volume and surface floorings. Overall the
      results of VOC, aldehydes, ketones and endotoxin indicate, in general, a low
      exposure level in classrooms. The observed concentrations of cat allergens should
      be considered as a meaningful exposure route and thus could be tackled within
      preventive programs.

PMID- 18348099
TI  - [Psychosocial behaviour and subjective experience specific to the course of study
      of medical students in their first and fifth years of study].
AB  - AIM: This study concerns the evaluation of study-related psychosocial risk
      factors and resources in medical students at the beginning and before the end of
      their course of studies. METHODS: Written questionnaires were filled out by
      medical students in Lubeck and Freiburg in their first and fifth years of study
      and analysed with three standard instruments (AVEM, SAM, F-Sozu). The response
      rate was 84.5% (n=435) in the first and 83.0% (n=351) in the fifth year of study.
      RESULTS: At the outset of their course of study, most of the students evinced
      behaviour and subjective experience patterns which were not deleterious to their
      health. Nevertheless, even at this point in time, 22.9% of the students showed a
      risk constellation with an excessive commitment to work and readiness to
      overstrain themselves. With 17.9% resignatory exhaustion with a highly
      restrictive subjective quality of life was found. In the fifth year of study,
      this proportion had increased to 23.3%, while the quality of health behaviour and
      subjective experience patterns deteriorated. Self-awareness and social support
      were augmented by comparison with norm samples. CONCLUSION: A portion of the
      medical students showed a risk constellation in behaviour and subjective
      experience at the very beginning of their studies. At the end, this tendency has
      significantly strengthened. The integration of teaching contents dealing with
      health promotion and successful coping with stress for the medical students
      themselves would therefore seem essential for the conservation of the health and
      working capacity of the students, as well as in order to prevent subsequent
      profession-specific mental stress and burn-out.

PMID- 18348100
TI  - [Occupational mental well-being--utopia or necessity?].
AB  - The remarkable social-medical and economical importance of psychic and
      psychosomatic diseases is empasised by broad public discussions. According to
      recent epidemiological findings, these kinds of health disorders are not only
      more frequent than assumed formerly, but they also have severe social
      consequences. Contrary to the trend of a lowering level of the ill population,
      during the last decade psychic diseases were leading with all legal health
      insurance companies to a rising trend in days of inability to work, which now
      seems to consolidate at a high level. In addition to this, nearly e very third
      premature loss of occupation induced by illnesses - far before having reached the
      regular age limit - with legally pension-insured persons is based on psychic
      diseases. With civil servants, each second premature service inability has its
      roots in such a kind of suffering. At present, the reasons for this development
      are being discussed controversially. Psychosocial loads of the globalised, market
      focused working sphere are regarded in this context as (sole) causing or at least
      as manifestation-promoting factors. The present article illuminates selected
      aspects of psychosomatic diseases concerning public health and the importance of
      work-associated psychosocial loads under consideration of the background of
      changes in society and working sphere. According to broad consent the setting
      "job" implies an enormous potential of prevention of psychic diseases, therefore,
      we will finally point out action options for an operational, psychosocial health
      promotion, which do not only focus on aspects of competition.

PMID- 18348101
TI  - [Amendment to the law governing the professional activities of physicians in
      "Medizinische Versorgungszentren"].
AB  - The amendment to the law governing the professional activities of physicians in
      general, free practice came into force on 1st January 2007 bringing important
      changes relevant to medical centres, which were first permitted by the government
      three years ago. Under the new regulations, for example, medical centres with the
      status of a private limited company now must provide a guarantee as a condition
      for the licence to operate. Some of the other most important new regulations
      include the abolishment of the restriction to practice in one place only and
      permission for physicians to hold positions in a hospital and a medical centre at
      the same time.

PMID- 18348102
TI  - Criminal liability research in vaccine administration by public health nurse: a
      case study of the Nantou vaccine administration case.
AB  - Immunization is recognized as a powerful public health tool in disease control
      and eradication. Registered nurses (RNs) are the principal health professionals
      responsible for administering vaccines, not only in terms of childhood
      immunization but also increasingly in administering travel vaccines and annual
      influenza vaccinations. The RN often provides leadership in developing and
      maintaining a high quality program. The legal position of nurses when
      administering a vaccine conflicts with their role as care providers, and nurses
      must be aware of their legal position when administering a vaccine that has not
      been individually prescribed by a doctor. A recent case involving a baby who died
      after receiving a vaccine administered by a public health nurse without a
      doctor's prescription resulted in the prosecutor initiating a prosecution against
      the nurse and chief of Health Bureau for a violation of Article 28 of the
      Physician's Act and the criminal law. Although the nurse and Bureau Chief were
      judged not guilty, the first trial court pointed out that the behavior of this
      nurse still violated Article 28. This reflects the conflict that exists between
      empirical practice and legal regulations. In order to guarantee that prophylactic
      inoculation is implemented properly under legitimate and effective conditions
      (specially in remote districts), in May 23, 2006, Legislative Yuan passed an
      amendment to Article 4 of the Communicable Disease Control Act, which specified
      that no public health nurse can be prosecuted for violations of Article 28 of the
      Physician's Act as a result of vaccine administration. In the future, nurses in
      clinics located in remote districts may conduct prophylactic inoculation work
      without fear of the terms of Article 28 and focus on implementing public
      prophylactic inoculation responsibilities. However, a public health nurse can
      still be liable for the malpractice in criminal law during the vaccination.
      Therefore, following procedure is still necessary in the conduct of vaccination
      duties.

PMID- 18348103
TI  - Menstrual health care behavior and associated factors among female elementary
      students in the Hualien region.
AB  - The purposes of this study were to measure menstrual knowledge, assess menstrual
      health care behavior and investigate the factors associated with menstrual health
      care behavior among fifth and sixth grade female students. The subjects were 417
      female students from 12 elementary schools in the Hualien region of Taiwan. The
      stratified cluster random sampling method was adopted. The questionnaire used in
      the study consisted of three sections: personal information, a menstrual
      knowledge questionnaire, and a menstrual health care behavior questionnaire. The
      results of this study show that the majority of the respondents felt that
      menstruation had an influence on their emotions (74.8%), daily life (73.1%),
      schoolwork (61.6%), and social interaction (50.1%). The total correct response
      rate for the menstrual knowledge questionnaire was 45.1%. There was a significant
      difference between aboriginal and non-aboriginal female students in terms of the
      correct answer rate for the menstrual knowledge questionnaire. The mean score for
      menstrual health care behavior was 2.66 (SD = 0.82). Elementary level female
      students who had better menarche preparation scored higher on the menstrual
      knowledge questionnaire, and those whose first period had already occurred felt
      more confident in their ability to execute proper menstrual health care behavior.
      The results prompted the recommendation to families and elementary schools to
      encourage students to improve their menstrual health care behavior during menses.

PMID- 18348104
TI  - Predictors of dysmenorrhea and self-care behavior among vocational nursing school
      female students.
AB  - The purposes of this study were to investigate: (a) differences in demographic
      characteristics between a group of with dysmenorrhea and a group without this
      condition, (b) the predictors of dysmenorrhea, and (c) self-care behavior for
      dysmenorrhea among vocational nursing school female students. A convenience
      sampling method was used. Freshmen from three vocational nursing schools located
      in southern Taiwan were recruited. 805 potential participants were surveyed with
      structured questionnaires, and 760 valid questionnaires were obtained. Results
      showed the average age of the participants to be 16.7 years. The prevalence rate
      of dysmenorrhea was 73.3%. Fifty percent of participants reported their menarche
      occurred between the ages of 12 to 14, 61.6% of them still didn't have regular
      menstruation, 83.9% had menstruation periods that lasted between 4 to 6 days,
      34.6% had received relevant health education, and 20.8% had visited a doctor for
      dysmenorrhea. There was a significant difference between the dysmenorrhea and non
      dysmenorrhea groups in terms of menstrual regularity and receipt of health
      education. Based on research results, we suggest improving female adolescents'
      self-care behavior against dysmenorrhea through enhanced health education in
      schools.

PMID- 18348105
TI  - Medical team satisfaction with nurse practitioner clinical performance.
AB  - The nurse practitioner (NP) system aims to enhance medical care quality, prevent
      and reduce human errors in medical care, and instill a cooperative spirit in
      medical teams. Nationally and international studies indicate a high level of
      satisfaction with the NP system from patients and their family. However, the
      expectations and satisfaction of medical teams with NP clinical performance have
      not yet been clearly delineated. In this research, a sample of 255 physicians,
      nurses, and other medical staff were recruited from a medical center in central
      Taiwan. Questionnaires given to this sample addressed the three major aspects of:
      "NP System", "clinical practice content", and "performance of clinical
      professional competency". The Content Validity Index (CVI) of the questionnaire
      was .8981, and Cronbach's reliability values for the three aspects were .88, .94,
      and .89, respectively. Results indicate that physicians and nurses have a
      significant difference of opinions with regard to the three aspects addressed.
      Physicians have higher recognition and satisfaction of the "NP system" and
      "performance of clinical professional competency". Nurses tend to see "clinical
      practice content" as the major aspect. In conclusion, physicians and other
      medical staff had very positive attitudes towards the NP system and believed the
      clinical competency performance could be improved.

PMID- 18348106
TI  - Pilot-testing the effects of a newly-developed silver yoga exercise program for
      female seniors.
AB  - This study aimed to pilot-test the health promotion effects of a silver yoga
      exercise program for female seniors. Using a one-group, pre-post test design, a
      convenience sample of 16 community-dwelling female seniors was recruited. The
      silver yoga exercise intervention was administered three times a week, 70 minutes
      per session, for four weeks. Data were collected at baseline and after completion
      of the four-week intervention. Results indicated that participants' body fat
      percentage and systolic blood pressure decreased, balance and range of motion on
      shoulder flexion and abduction improved, and sleep disturbance was minimized (all
      p < .05). Preliminary evidence supports that the silver yoga exercise program
      provides positive effects on the promotion of good health in female seniors
      living in the communities.

PMID- 18348107
TI  - Geographical variations in elderly disability in Taiwan.
AB  - Inequality in health has long been a topic of discussion. The purpose of this
      research was to provide estimates of the proportions of elderly who had
      difficulties in activities of daily living in each of the 23 administrative areas
      of Taiwan, and to assess if there was geographical disparity in disability across
      areas. A nationally representative sample of 303,545 subjects was selected for
      interview. Among the subjects selected for interview, 239,861 completed the
      survey, a completion rate of about 80%. For the purpose of this research, only
      those aged 65 years or older were included (N = 114,873) in the analyses. Non
      standardized and standardized prevalences of disability were presented for each
      of the 23 administrative areas in Taiwan, and geographical distribution of
      elderly disability was plotted. Results show that significant difference in
      disability prevalence exists among administrative districts, even after adjusting
      for age and sex structure of the population. Moreover, the extent of gender
      disparity also varied from one area to another. The western region, in general,
      had lower disability prevalence than the eastern region. Findings imply that
      since disability prevalence varied significantly across administrative areas,
      funding for long-term care should not be allocated based on the number of elderly
      population in an administrative area. Areas with high prevalence should identify
      reasons for their high prevalence rates and implement proper interventions.

PMID- 18348108
TI  - Factors associated with smoking cessation among male adults with coronary heart
      disease in Taiwan.
AB  - The purpose of this study was to examine factors associated with smoking
      cessation behavior among male adult smokers hospitalized for a cardiac event in
      Taiwan during the three-month period following their discharge from hospital. A
      longitudinal correlational design using two structured questionnaires and two
      phone interviews was employed to collect data. A convenient sampling was adopted.
      Among the 250 potential participants recruited, 148 provided completed data and
      were included as study subjects. Three months after hospital discharge, 43.9% of
      subjects were defined as "continuous abstainers" (i.e., not a single cigarette
      puff taken during this period), 33.8% were "non-continuous abstainers" (i.e.,
      abstained for at least 1 day, but had smoked at some point during this period),
      and 22.3% were "continuous smokers" (i.e., had not abstained from smoking for any
      period equal to or exceeding 24 hours during this period). Multivariate analysis
      (hierarchical logistic regression) revealed that subjects with higher self
      efficacy in not smoking and greater perceived positive family support were more
      likely to quit smoking for at least 24 hours (i.e., "attempters"). Attempters who
      stayed in hospital for longer periods of time, had higher self-efficacy in not
      smoking or perceived more positive and fewer negative family support behaviors
      were more likely to become continuous abstainers. These results suggest that self
      efficacy and family support should be addressed in any intervention program
      targeting smoking cessation in male patients with coronary heart disease.

PMID- 18348109
TI  - Comparative study of children's self-concepts and parenting stress between
      families of children with epilepsy and asthma.
AB  - The purpose of the present study was to conduct a comparative study on families
      of children with epilepsy and asthma with regard to the variables of children's
      self-concepts and parenting stress. While past research has indicated higher
      rates of behavioral problems in children with epilepsy, behavioral problems were
      associated primarily with children's self-concept. How an individual assesses his
      or herself impacts significantly upon self conceptualization and the attainment
      of a stable concept about oneself as an individual is a critical development
      factor during an individual's cognitive development stage. Nevertheless, specific
      factors related to such have not previously been well delineated. Forty-eight
      children, 8 to 13 years of age with epilepsy, and 54 children in the same age
      range with asthma were investigated for this study. Parents of subjects were also
      involved in this study. The self-concepts of subject children were assessed using
      the Harter's Self-Perception Profile for Children (SPPC). Parenting stress was
      measured using Abidin's Parenting Stress Index (PSI)/long form. Children's
      demographic variables and illness severity were also measured as potential risk
      factors. Results showed significant differences between the two groups in terms
      of self-concept and parenting stress, with epileptic children returning
      significantly lower self-concept scores in 3 SPPC subscales. Demographic
      variables and illness conditions were not found to be effective predictors of
      parenting stress. Level of parenting stress was revealed to be significantly
      associated with children's self-concept in the epilepsy group. Results suggest
      that parents of children with epilepsy will benefit from coping strategies that
      may help lower parenting stress levels and influence positively upon children's
      self-concept. In addition to providing regular drug therapy, providing further
      support is needed.

PMID- 18348110
TI  - The relationship between TV/computer time and adolescents' health-promoting
      behavior: a secondary data analysis.
AB  - Television and computers provide significant benefits for learning about the
      world. Some studies have linked excessive television (TV) watching or computer
      game playing to disadvantage of health status or some unhealthy behavior among
      adolescents. However, the relationships between watching TV/playing computer
      games and adolescents adopting health promoting behavior were limited. This study
      aimed to discover the relationship between time spent on watching TV and on
      leisure use of computers and adolescents' health promoting behavior, and
      associated factors. This paper used secondary data analysis from part of a health
      promotion project in Taoyuan County, Taiwan. A cross-sectional design was used
      and purposive sampling was conducted among adolescents in the original project. A
      total of 660 participants answered the questions appropriately for this work
      between January and June 2004. Findings showed the mean age of the respondents
      was 15.0 +/- 1.7 years. The mean numbers of TV watching hours were 2.28 and 4.07
      on weekdays and weekends respectively. The mean hours of leisure (non-academic)
      computer use were 1.64 and 3.38 on weekdays and weekends respectively. Results
      indicated that adolescents spent significant time watching TV and using the
      computer, which was negatively associated with adopting health-promoting
      behaviors such as life appreciation, health responsibility, social support and
      exercise behavior. Moreover, being boys, being overweight, living in a rural
      area, and being middle-school students were significantly associated with
      spending long periods watching TV and using the computer. Therefore, primary
      health care providers should record the TV and non-academic computer time of
      youths when conducting health promotion programs, and educate parents on how to
      become good and healthy electronic media users.

PMID- 18348112
TI  - Selective oxidation of aliphatic C-H bonds in the synthesis of complex molecules.

PMID- 18348111
TI  - Enantioselective phase-transfer-catalyzed intramolecular aza-Michael reaction:
      effective route to pyrazino-indole compounds.

PMID- 18348113
TI  - Coordination chemistry of ene-1,1-diamines and a prototype "carbodicarbene".

PMID- 18348114
TI  - Betablockers at work: the crystal structure of the beta2-adrenergic receptor.

PMID- 18348115
TI  - Total synthesis of enzyme inhibitor spirastrellolide A--stereochemical
      confirmation.

PMID- 18348116
TI  - A molecular dynamics study of the ASC and NALP1 pyrin domains at neutral and low
      pH.
AB  - The pyrin domain is one of four subfamilies of the death domain superfamily of
      proteins, all members of which share a similar three-dimensional fold with a
      structure comprising five or six antiparallel alpha-helices. The pyrin domain of
      the ASC (six-helical fold) and of the NALP1 (five-helical fold) proteins were
      simulated at two different pH values, 3.7 and 6.5, with two different force-field
      parameter sets, and the molecular dynamics simulation trajectories were compared
      to NMR experimental data. The two force fields that were used did not show very
      different results. The simulations of NALP1 at pH 6.5 largely satisfied the
      experimental NOE atom-atom distance bounds that were measured at pH 6.5, and
      preserved its tertiary structure. The simulations at pH 3.7 showed a denaturation
      of the protein. The simulations of ASC at pH 3.7 only satisfied the experimental
      NOE atom-atom distance bounds that were measured at pH 3.7 if either three acidic
      side chains (Asp48, Glu64 and Asp75) or only two (Glu64 and Asp75) were not
      protonated. This indicates that the ASC tertiary structure is stabilized by salt
      bridges at low pH. A corresponding analysis for NALP1 at pH 3.7 only yielded one
      possible salt bridge, but this did not stabilize the tertiary structure at low
      pH. The results show that the particular protonation states of acidic side chains
      in the protein interior might be crucial to properly modeling these proteins at
      low pH.

PMID- 18348117
TI  - Paying for performance: the power of incentives over habits.

PMID- 18348118
TI  - Ethanol as hydrogen donor: highly efficient transfer hydrogenations with
      rhodium(I) amides.

PMID- 18348119
TI  - Phototriggering of cell adhesion by caged cyclic RGD peptides.

PMID- 18348120
TI  - METAMORPhos: adaptive supramolecular ligands and their mechanistic consequences
      for asymmetric hydrogenation.

PMID- 18348121
TI  - Proximicins A, B, and C-antitumor furan analogues of netropsin from the marine
      actinomycete Verrucosispora induce upregulation of p53 and the cyclin kinase
      inhibitor p21.

PMID- 18348122
TI  - The direct conversion of light into continuous mechanical energy by
      photoreversible self-assembly: a prototype of a light-powered engine.

PMID- 18348123
TI  - Aerobic alcohol oxidation coupled to palladium-catalyzed alkene hydroarylation
      with boronic esters.

PMID- 18348124
TI  - Catalytic abatement of nitrous oxide coupled with selective production of
      hydrogen and ethylene.

PMID- 18348125
TI  - Light-powered electrical switch based on cargo-lifting azobenzene monolayers.

PMID- 18348126
TI  - The complete stereochemistry of the enzymatic dehydration of 4-hydroxybutyryl
      coenzyme A to crotonyl coenzyme A.

PMID- 18348127
TI  - An ESI-MS/MS method for screening of small-molecule mixtures against glycogen
      synthase kinase-3beta (GSK-3beta).
AB  - Glycogen synthase kinase-3beta (GSK-3beta) is involved in the
      hyperphosphorylation of previously phosphorylated (primed) substrates, and is
      currently assayed using an approach based on the incorporation of gamma-(32)P
      radiolabelled isotopes into substrate peptides. The requirement to detect
      hyperphosphorylation of a primed substrate poses a particular challenge for
      development of a high-throughput screening assay, as many current kinase assays
      are designed to produce a signal in the presence of any phosphorylation site, and
      thus are only suitable for beta-unphosphorylated substrates. Herein, we have
      developed an electrospray-ionization tandem mass spectrometry (ESI-MS/MS) assay
      to allow for direct detection of a hyperphosphorylated product which is formed in
      a solution reaction involving a primed peptide substrate (GSM peptide) and GSK
      3beta. Optimum reaction conditions (level of Mg(2+), buffer type, ionic strength,
      pH, enzyme concentration, and reaction time) were established to both maintain
      the activity of GSK-3beta and allow for substrate and product quantification
      through ESI/MS/MS. We show that the MS-based assay allows for rapid determination
      of GSK-3beta activity from reaction volumes of approximately 40 microL and that
      it can be used to assess IC(50) values and the site of action of known
      inhibitors. It also can be used for automated screening of small-molecules
      mixtures to identify inhibitors of GSK-3beta.

PMID- 18348128
TI  - Covalent linkage mediates communication between ACP and TE domains in modular
      polyketide synthases.
AB  - Polyketide natural products such as erythromycin A and epothilone are assembled
      on multienzyme polyketide synthases (PKSs), which consist of modular sets of
      protein domains. Within these type I systems, the fidelity of biosynthesis
      depends on the programmed interaction among the multiple domains within each
      module, centered around the acyl carrier protein (ACP). A detailed understanding
      of interdomain communication will therefore be vital for attempts to reprogram
      these pathways by genetic engineering. We report here that the interaction
      between a representative ACP domain and its downstream thioesterase (TE) is
      mediated largely by covalent tethering through a short "linker" region, with only
      a minor energetic contribution from protein-protein molecular recognition. This
      finding helps explain in part the empirical observation that TE domains can
      function out of their normal context in engineered assembly lines, and supports
      the view that overall PKS architecture may dictate at least a subset of
      interdomain interactions.

PMID- 18348129
TI  - From valleys to ridges: exploring the dynamic energy landscape of single membrane
      proteins.
AB  - Membrane proteins are involved in essential biological processes such as energy
      conversion, signal transduction, solute transport and secretion. All biological
      processes, also those involving membrane proteins, are steered by molecular
      interactions. Molecular interactions guide the folding and stability of membrane
      proteins, determine their assembly, switch their functional states or mediate
      signal transduction. The sequential steps of molecular interactions driving these
      processes can be described by dynamic energy landscapes. The conceptual energy
      landscape allows to follow the complex reaction pathways of membrane proteins
      while its modifications describe why and how pathways are changed. Single
      molecule force spectroscopy (SMFS) detects, quantifies and locates interactions
      within and between membrane proteins. SMFS helps to determine how these
      interactions change with temperature, point mutations, oligomerization and the
      functional states of membrane proteins. Applied in different modes, SMFS explores
      the co-existence and population of reaction pathways in the energy landscape of
      the protein and thus reveals detailed insights into local mechanisms, determining
      its structural and functional relationships. Here we review how SMFS extracts the
      defining parameters of an energy landscape such as the barrier position, reaction
      kinetics and roughness with high precision.

PMID- 18348130
TI  - A highly selective colorimetric aqueous sensor for mercury.
AB  - A new colorimetric mercury sensor is reported based on binding to terpyridine
      derivatives. It is able to selectively detect Hg II ions over a number of
      environmentally relevant ions including Ca II, Pb II, Zn II, Cd II, Ni II, Cu II,
      and others. The response time upon exposure to Hg II is instantaneous. By the
      "naked eye," the detection limit of Hg II is 2 ppm (25 microM) in solution. With
      a spectrometer, this detection limit is increased down to 2 ppb (25 nM), which is
      the current EPA standard for drinking water. The significant problem of mercury
      poisoning requires new methods of detection that are sensitive and selective.
      Here we report a new simple system that takes advantage of the unique optical
      properties generated by terpyiridine-Hg complexes.

PMID- 18348131
TI  - pH-Triggered dethreading-rethreading and switching of cucurbit[6]uril on bistable
      [3]pseudorotaxanes and [3]rotaxanes.
AB  - A series of water-soluble [3]rotaxanes-(n+2) and [3]pseudorotaxanes-(n+2) with
      short (propyl, n=1) and long (dodecyl, n=10) aliphatic spacers have been prepared
      in high yields by a 1,3-dipolar cycloaddition reaction catalyzed by
      cucurbit[6]uril (CB6). The pH-triggered dethreading and rethreading of CB6 on
      these pseudorotaxanes was monitored by 1H NMR spectroscopy. A previously reported
      [3]rotaxane-12 that is known to behave as a bistable molecular switch has two
      recognition sites for CB6, that is, the diaminotriazole moieties and the dodecyl
      spacer. By changing the pH of the system, it is possible to observe more than one
      state in the shuttling process. At low pH values both CB6 units are located on
      the diaminotriazole moieties owing to an ion-dipole interaction, whereas at high
      pH values both of the CB6 units are located on the hydrophobic dodecyl spacer.
      Surprisingly, the CB6 units shuttle back to their initial state very slowly after
      reprotonation of the axle. Even after eighteen days at room temperature, only
      about 50 % of the CB6 units had relocated back onto the diaminotriazole moieties.
      The rate constants for the shuttling processes were measured as a function of
      temperature over the range from 313 to 333 K and the activation parameters
      (enthalpy, entropy, and free energy) were calculated by using the Eyring
      equation. The results indicate that this [3]rotaxane behaves as a kinetically
      controlled molecular switch. The switching properties of [3]rotaxane-3 have also
      been studied. However, even under extreme pH conditions this rotaxane has not
      shown any switching action, which confirms that the propyl spacer is too short to
      accommodate CB6 units.

PMID- 18348132
TI  - Heterometallic [Mn5-Ln4] single-molecule magnets with high anisotropy barriers.
AB  - The reaction of [Mn6O2(Piv)(10)(4-Me-py)(2.5)(PivH)(1.5)] (1) (py: pyridine, Piv:
      pivilate) with N-methyldiethanolamine (mdeaH2) and Ln(NO3)3 x 6 H2O in MeCN leads
      to a series of nonanuclear compounds
      [Mn5Ln4(O)6(mdea)2(mdeaH)2(Piv)6(NO3)4(H2O)2]2 MeCN (Ln=Tb(III) (2), Dy(III) (3),
      Ho(III) (4), Y(III) (5)). Single-crystal X-ray diffraction shows that compounds 2
      5 are isostructural, with the central core composed of two distorted
      {Mn(IV)Mn(III)Ln2O4} cubanes sharing a Mn(IV) vertex, representing a new
      heterometallic 3d-4f motif for this class of ligand. The four new compounds
      display single-molecule magnet (SMM) behaviour, which is modulated by the
      lanthanide ion used. Moreover, the values found for Delta(eff) and tau(o) for 3
      of 38.6 K and 3.0 x 10(-9) s respectively reveal that the complex 3 exhibits the
      highest energy barrier recorded so far for 3d-4f SMMs. The slow relaxation of the
      magnetisation for 3 was confirmed by mu-SQUID measurements on an oriented single
      crystal and the observation of M versus H hysteresis loops below 1.9 K.

PMID- 18348133
TI  - Tyrosinase-like reactivity in a Cu(III)2(mu-O)2 species.

PMID- 18348134
TI  - Sensitized detection of inhibitory fragments and iterative development of non
      peptidic protease inhibitors by dynamic ligation screening.

PMID- 18348135
TI  - A heterobimetallic Pd/La/Schiff base complex for anti-selective catalytic
      asymmetric nitroaldol reactions and applications to short syntheses of beta
      adrenoceptor agonists.

PMID- 18348136
TI  - Enantioselective synthesis of an atropisomeric diaryl ether.

PMID- 18348137
TI  - Repeatability of joint proprioception and muscle torque assessment in healthy
      children and in children diagnosed with hypermobility syndrome.
AB  - BACKGROUND: Impairment of joint proprioception in patients with hypermobility
      syndrome (HMS) has been well documented. Both joint proprioception and muscle
      torque are commonly assessed in patients with musculoskeletal complaints. It is
      unknown, however, if these measures change significantly on repeated application
      in healthy children and in children with HMS. AIM: To investigate the between
      days repeatability of joint proprioception and muscle torque in these groups.
      METHODS: Twenty children (10 healthy and 10 with HMS), aged eight to 15 years,
      were assessed on two separate occasions (one week apart) for joint kinaesthesia
      (JK), joint position sense (JPS), and the extensor and knee flexor muscle torque
      of the knee. JK was measured using threshold to detection of passive movement.
      JPS was measured using the absolute angular error (AAE; the absolute difference
      between the target and perceived angles). Knee extensor and flexor muscle torque
      was normalized to body weight. RESULTS: Intra-class correlation coefficients
      (ICC) for JK, extensor and flexor muscle torque were excellent in both groups
      (range 0.83 to 0.98). However, ICC values for JPS tests were poor to moderate in
      the two groups (range 0.18 to 0.56). 95% limits of agreement (LOA) were narrow in
      both cohorts for JK and muscle torque (indicating low systematic error) but wide
      for the JPS tests. 95% LOA also demonstrated that the measuring instruments used
      in this study had low between-days systematic error. CONCLUSIONS: Based on ICC
      and 95% LOA, the repeatability of JK and muscle torque measurements was excellent
      in both healthy children and those with HMS. The JPS test can only be assessed
      with poor to moderate repeatability. The use of the JPS test in these children
      should be undertaken with caution.

PMID- 18348139
TI  - Method for tracking nanogel particles in vivo and in vitro.
AB  - Hydrogels made of N-isopropylacrylamide (NIPA) can be synthesized in the form of
      highly monodispersed nanoparticles. After synthesis, NIPA hydrogel nanoparticles
      (nanogels) can be labeled by Alexa Fluor 488 carboxylic acid, 2,3,5,6
      tetrafluorophenyl ester through amine-terminated functional groups. This choice
      of dye is complementary to other biological labeling methods for in vivo studies.
      When the nanogel/dye nanoparticles are injected into rabbits, they can be imaged
      via tissue sectioning and confocal microscopy, while nanoparticle concentration
      can be determined by fluorescent microplate assays. Time-course persistence of
      nanoparticles in the circulatory system can be readily tracked by direct assay of
      plasma and urine samples using 485 nm excitation and 538 emission wavelengths to
      keep background fluorescence to nearly the same level as that found using an
      empty well. Depending upon how the nanoparticles are injected, circulatory system
      concentrations can reach high concentrations and diminish to low levels or
      gradually increase and gradually decrease over time. Injection in the femoral
      artery results in a rapid spike in circulating nanogel/dye concentration, while
      injection into the renal artery results in a more gradual increase.

PMID- 18348140
TI  - Production and characterization of pharmacologically active recombinant human
      phosphodiesterase 4B in Dictyostelium discoideum.
AB  - Phosphodiesterase 4B (PDE4B) is an important therapeutic target for asthma and
      chronic obstructive pulmonary disease. To identify PDE4 subtype-specific
      compounds using high-throughput assays, full-length recombinant PDE4 proteins are
      needed in bulk quantity. In the present study, full-length human PDE4B2 was
      expressed in the cellular slime mould Dictyostelium discoideum (Dd). A cell
      density of 2 x 10(7) cells/mL was obtained and up to 1 mg/L recombinant PDE4B2
      was purified through Ni-NTA affinity chromatography. The expressed protein was
      soluble and its activity was comparable to PDE4B2 protein expressed in mammalian
      cells (K(m)=1.7 microM). The functional significance of the Dd expression system
      is supported by the demonstration that, in concert with proteins expressed in
      mammalian systems, there are no major changes in the affinity for PDE4B2
      inhibitors and substrates. These findings thus provide the first evidence that Dd
      can be utilized for the expression and purification of functionally active full
      length human PDE4B2 in large amounts required for high-throughput screening of
      pharmacologically active compounds against this therapeutic target.

PMID- 18348141
TI  - Effect of p53 codon 72 genotype on breast cancer survival depends on p53 gene
      status.
AB  - In vitro studies suggest that p53 codon 72 genotype alters the apoptotic capacity
      of p53 protein, with the 72 arginine (R) form of wild-type p53 harboring a
      greater apoptosis-inducing potential than the 72 proline (P) variant. The aim of
      this study was to investigate whether the association between the p53 codon 72
      genotype and breast cancer survival was modified by p53 gene status. In our
      study, we examined the p53 codon 72 genotype and p53 mutations (through exons 4
      9) in paraffin-embedded specimens from 414 breast cancer patients with a median
      follow-up of 8.2 years. We report that the p53 codon 72 genotype was
      significantly associated with disease-free survival (DFS, p = 0.02) but not with
      disease-specific survival (DSS, p = 0.24) in the entire study population (n =
      414). In contrast, the codon 72 genotype was strongly associated with both DFS (p
      = 0.001) and DSS (p = 0.04) among patients with a wild-type p53 tumor (n = 346),
      patients with the P/P variant had worse DFS and DSS than did those with the P/R
      or R/R variant in this subgroup of patients. More importantly, as compared with
      the P/R or R/R variant, the P/P variant remained an independent prognostic factor
      of DFS among patients with a wild-type p53 tumor (HR = 2.5; 95%CI = 1.4-4.4; p =
      0.003). We conclude that the effect of p53 codon 72 genotype on breast cancer
      survival is dependent on p53 gene status, the P/P variant is strongly associated
      with poor prognosis among patients with a wild-type p53 tumor.

PMID- 18348142
TI  - Risk factors for invasive squamous cell carcinoma of the vulva and vagina-
      population-based case-control study in Denmark.
AB  - The etiology of vulvar and vaginal squamous cell carcinoma (VV-SCC) has received
      little attention. A total of 182 women with invasive VV-SCC (116 with VV
      SCC(vulva), 66 with VV-SCC(vagina)), 164 uterine corpus cancer controls and 518
      population controls were interviewed in a population-based case-control study in
      Denmark, and 87 (48%) of the VV-SCC cases had tissue samples examined for human
      papillomavirus (HPV) DNA using the GP5+/6+ PCR-EIA assay and subsequent reverse
      line blotting for HPV typing. Logistic regression-derived odds ratios with 95%
      confidence intervals served as relative risks. Cervical cancer-associated high
      risk HPVs (hrHPVs) were detectable in most (89%) examined cases of VV-SCC(vagina)
      and in half (50%) of cases of VV-SCC(vulva) (p < 0.001). In site-specific
      multivariate logistic regression analyses, statistically significant risk factors
      for both VV-SCC(vulva) and VV-SCC(vagina) included measures of hrHPV exposure
      (anogenital warts for VV-SCC(vulva); cervical neoplasia and poor genital hygiene
      for VV-SCC(vagina)), tobacco smoking and alcohol consumption. Furthermore,
      socioeconomic variables (marital status and years at school) were associated with
      risk of VV-SCC(vulva). Comparing hrHPV-positive and hrHPV-negative VV-SCCs in
      polytomous logistic regression analysis revealed that tobacco smoking and
      cervical neoplasia were significant risk factors only for hrHPV-positive VV-SCCs.
      Our study shows that VV-SCC(vulva) and VV-SCC(vagina) share measures of prior
      hrHPV exposure, tobacco smoking and alcohol consumption as statistically
      significant risk factors. HPV vaccination programs aimed at reducing the burden
      of cervical cancers are likely to also provide considerable protection against VV
      SCCs.

PMID- 18348143
TI  - Protective role of 1 alpha, 25-dihydroxyvitamin D3 against oxidative stress in
      nonmalignant human prostate epithelial cells.
AB  - Overproduction of reactive oxygen species (ROS), through either endogenous or
      exogenous sources, could induce DNA damage, and accumulation of DNA damage might
      lead to multistep carcinogenesis. The antioxidative effects of vitamin D have
      been suggested by epidemiological and many in vitro and in vivo laboratory
      studies. While exploring the antioxidative effects of vitamin D in prostate
      cells, we found that the active form of vitamin D, 1 alpha, 25-dihydroxyvitamin
      D(3) (1,25-VD), can protect nonmalignant human prostate epithelial cell lines,
      BPH-1 and RWPE-1, but not malignant human prostate epithelial cells, CWR22R and
      DU 145, from oxidative stress-induced cell death. Glucose-6-phosphate
      dehydrogenase (G6PD), a key antioxidant enzyme, was dose- and time-dependently
      induced by 1,25-VD. Mechanistic studies using chromatin immunoprecipitation
      (ChIP) assay revealed that a direct repeat-3 (DR3) vitamin D response element
      located in the first intron of the G6PD genome can be bound by liganded vitamin D
      receptor, thereby regulating G6PD gene expression. Increasing G6PD activity and
      glutathione level by 1,25-VD can scavenge cellular ROS. Moreover, the protective
      effects of 1,25-VD were abolished by dehydroepiandrosterone, a noncompetitive
      inhibitor of G6PD activity. Together, our results showed that 1,25-VD can protect
      nonmalignant prostate cells from oxidative stress-induced cell death by
      elimination of ROS-induced cellular injuries through transcriptional activation
      of G6PD activity. The antioxidative effect of vitamin D strengthens its roles in
      cancer chemoprevention and adds to a growing list of beneficial effects of
      vitamin D against cancer.

PMID- 18348144
TI  - Mouse mammary tumor virus-like env sequences in human breast cancer.
AB  - Mouse mammary tumor virus (MMTV) has long been known as a causal agent of breast
      cancer in mice. To date, varied MMTV-like envelope gene (env) sequences have been
      identified in up to 74% of human breast cancers. However, the role and origin of
      these MMTV-like sequences in human breast cancer remain uncertain. Our study was
      initiated to study the integration of MMTV-like env sequences in human breast
      cancer. PCR screening has identified 28 (56%) Australian breast cancer specimens
      and 7 (87.5%) human breast cancer cell lines to be positive for MMTV-like env
      sequence. In the MCF-7 genome, a fragment containing an MMTV-like env sequence of
      approximately 1.9 kb plus a downstream rodent-like sequence of approximately 200
      bp was found to be integrated into a bacterial-like beta-lactamase sequence by
      insertional mutagenesis. The identified MMTV-rodent fragment is present in some
      MCF-7 sublines but absent in the screened specimens and other cell lines.
      Sporadic mutations found in this fragment indicate it has multiple copies in the
      MCF-7 genome. Sequence analysis has identified a novel ORF of approximately 1.6
      kb which is 94-99% identical to MMTV env genes. RT-PCR was performed on the MCF-7
      cDNA but no MMTV-like env transcript was detected. This is the first report to
      reveal the locus of MMTV-like env sequence in human cells. The MMTV-like env
      sequence was shown to be distinct from the human endogenous retroviral sequences
      and is closely related to rodents.

PMID- 18348146
TI  - Latest developments in the catalytic application of nanoscaled neutral group 8-10
      metals.
AB  - In the last few decades, the synthesis and catalytic application of nanoscaled
      particles prepared from Group 8-10 (formerly Group VIIIB) elements have been
      widely explored and have achieved promising results. The innovative use of these
      nanoparticle catalysts may provide new opportunities in the efficient combination
      of conventionally used homogenous and heterogeneous catalysts. Conventional
      homogeneous catalysts pose extraction and recycling difficulties when dealing
      with metal complexes and/or ligands, whereas heterogeneous catalysts generally
      require more pressing experimental conditions, such as high temperatures and high
      pressures, to be effective. Therefore, to solve these problems, the synthesis and
      use of nanoparticle catalysts as replacements for conventional catalytic systems
      is a breakthrough owing to their improved handling and environmental and economic
      aspects. This Focus Review primarily addresses the catalytic applications of
      neutral Group 8-10 nanoparticles with an average size of less than 10 nm, and
      also includes a discussion of commonly used synthetic methodology.

PMID- 18348147
TI  - Total synthesis of (+)-neopeltolide by a Prins macrocyclization.

PMID- 18348148
TI  - Synthesis of fluorinated dienes by palladium-catalyzed coupling reactions.
AB  - The synthesis of partly fluorinated 1,3- and 1,4-dienes by palladium-catalyzed
      coupling makes these compounds available on the laboratory scale. Several
      catalyst systems were tested to maximize the yields and minimize the by-products.
      The molecular structures of 1,1,2,4,4-pentafluorobutadiene, chloro(N,N'
      tetramethylethylenediamine)(trifluorovinyl)zinc, PCy(2)R, and P(O)Cy(2)R
      (Cy=cyclohexyl, R=2-(1-naphthyl)phenyl) were elucidated by X-ray crystallography.

PMID- 18348150
TI  - Exploiting threefold symmetry in asymmetric catalysis: the case of
      tris(oxazolinyl)ethanes ("trisox").
AB  - Rotational molecular symmetry, modularity and other aspects of ligand design have
      played a role in the development of a new class of stereodirecting ligands. The
      use of highly symmetrical, stereodirecting ligands may reduce the number of
      transition states and diastereomeric reaction intermediates and, in favourable
      cases, this degeneration of alternative reaction pathways may lead to high
      stereoselectivity in catalytic reactions and greatly simplifies the analysis of
      such transformations. In this concept article, we describe the way in which these
      considerations have played a role in the development of a new class of
      stereodirecting ligands. Tris(oxazolinyl)ethanes ("trisox") have proved to be
      versatile ligand systems for the development of enantioselective catalysts of the
      d- and f-block metals employed in a wide range of catalytic conversions. These
      include Lewis acid catalysed transesterifications, C-C and C-N coupling
      reactions, the catalytic polymerisation of alpha-olefins as well as Pd-catalysed
      allylic alkylations. An overview of the current state of this field is given and
      the potential for further development will be highlighted.

PMID- 18348151
TI  - Stepwise oxidation of the stannole dianion.
AB  - Tin oxidation of stannole dianion 1 with 1.3 equivalents of oxygen gave
      terstannole-1,3-dianion 3. The non-aromatic nature of 3 was confirmed by X-ray
      crystallographic analysis. Treatment of 1 with 1,2-dibromoethane (3 equiv) gave
      poly(1,1-stannole) 4, the formation of which was proven by reduction of 4 with
      lithium to revert to the starting dianion 1. Reaction of 1 with 1,2-dibromoethane
      (3 equiv) in the presence of phenyllithium gave phenyl-capped ter(1,1-stannole)
      7. The electronic absorption spectra of newly obtained stannoles were also
      measured.

PMID- 18348152
TI  - The mystery of perpendicular fivefold axes and the fourth dimension in
      intermetallic structures.
AB  - The structures of eight related known intermetallic structure types are the
      impetus to this paper: Li21Si5, Mg44Rh7, Zn13(Fe,Ni)2, Mg6Pd, Na6Tl, Zn91Ir11,
      Li13Na29Ba19, and Al69Ta39. All belong to the F43m space group, have roughly 400
      atoms in their cubic unit cells, are built up at least partially from the gamma
      brass structure, and exhibit pseudo-tenfold symmetric diffraction patterns. These
      pseudo-tenfold axes lie in the {110} directions, and thus present a paradox. The
      {110} set is comprised of three pairs of perpendicular directions. Yet no 3D
      point group contains a single pair of perpendicular fivefold axes (by Friedel's
      Law, a fivefold axis leads to a tenfold diffraction pattern). The current work
      seeks to resolve this paradox. Its resolution is based on the largest of all 4D
      Platonic solids, the 600-cell. We first review the 600-cell, building an
      intuition discussing 4D polyhedroids (4D polytopes). We then show that the
      positions of common atoms in the F43m structures lie close to the positions of
      vertices in a 3D projection of the 600-cell. For this purpose, we develop a
      projection method that we call intermediate projection. The introduction of the
      600-cell resolves the above paradox. This 4D Platonic solid contains numerous
      orthogonal fivefold rotations. The six fivefold directions that are best
      preserved after projection prove to lie along the {110} directions of the F43m
      structures. Finally, this paper shows that at certain ideal projected cluster
      sizes related to one another by the golden mean (tau=(1+ radical 5)/2),
      constructive interference leading to tenfold diffraction patterns is optimized.
      It is these optimal values that predominate in actual F43m structures. Explicit
      comparison of experimental cluster sizes and theoretically derived cluster sizes
      shows a clear correspondence, both for isolated and crystalline pairs of
      projected 600-cells.

PMID- 18348153
TI  - Wrestling off RAD51: a novel role for RecQ helicases.
AB  - Homologous recombination (HR) is essential for the accurate repair of DNA double
      strand breaks and damaged replication forks. However, inappropriate or aberrant
      HR can also result in genome rearrangements. The maintenance of cell viability
      is, therefore, a careful balancing act between the benefits of HR (the error-free
      repair of DNA strand breaks) and the potential detrimental outcomes of HR
      (chromosomal rearrangements). Two papers have recently provided a mechanistic
      insight into how HR may be tempered by RecQ helicases to prevent genome
      instability and diseases that are a consequence of this, such as cancer.

PMID- 18348154
TI  - Multicellular behavior in bacteria: communication, cooperation, competition and
      cheating.
AB  - The sociobiology of bacteria, largely unappreciated and ignored by the
      microbiology research community two decades ago is now a major research area,
      catalyzed to a significant degree by studies of communication and cooperative
      behavior among the myxobacteria and in quorum sensing (QS) and biofilm formation
      by pseudomonads and other microbes. Recently, the topic of multicellular
      cooperative behaviors among bacteria has been increasingly considered in the
      context of evolutionary biology. Here we discuss the significance of two recent
      studies of the phenomenon of "cheating" mutants and their exploitation of
      cooperating microbial populations of Pseudomonas aeruginosa.

PMID- 18348155
TI  - Multifunctional fourfold interpenetrating diamondoid network: gas separation and
      fabrication of palladium nanoparticles.
AB  - A fourfold interpenetrating diamondoid network, [{[Ni(cyclam)]2-(mtb)}(n)].8n
      H2O.4n DMF (1) (MTB=methanetetrabenzoate, DMF=dimethylformamide), has been
      assembled from [Ni(cyclam)][ClO4]2 (cyclam=1,4,8,11-tetraazacyclotetradecane) and
      methanetetrabenzoic acid (H4MTB) in DMF/H2O (7:3, v/v) in the presence of
      triethylamine (TEA). Despite the high-fold interpenetration, 1 generates 1D
      channels that are occupied by water and DMF guest molecules. Solid 1, after
      removal of guest molecules, exhibits selective gas adsorption behavior for H2,
      CO2, and O2 rather than N2 and CH4, suggesting possible applications in gas
      separation technologies. In addition, solid 1 can be applied in the fabrication
      of small Pd (2.0+/-0.6 nm) nanoparticles without any extra reducing or capping
      agent because a Ni II macrocyclic species incorporated in 1 reduces Pd II ions to
      Pd 0 on immersion of 1 in the solution of Pd(NO3)2.2H2O in MeCN at room
      temperature.

PMID- 18348156
TI  - Gold-nanorod-based sensing of sequence specific HIV-1 virus DNA by using hyper
      Rayleigh scattering spectroscopy.
AB  - Infectious diseases caused by the human immunodeficiency virus (HIV) remain the
      leading killers of human beings worldwide, and function to destabilize societies
      in Africa, Asia, and the Middle East. Driven by the need to detect the presence
      of HIV viral sequence, here we demonstrate that the second-order nonlinear
      optical (NLO) properties of gold nanorods can be used for screening HIV-1 viral
      DNA sequence without any modification, with good sensitivity (100 pico-molar) and
      selectivity (single base-pair mismatch). The hyper-Rayleigh scattering (HRS)
      intensity increases 45 times when a label-free 145-mer, ss-gag gene DNA, was
      hybridized with 100 pM target DNA. The mechanism of HRS intensity change has been
      discussed with experimental evidence for higher multipolar contribution to the
      NLO response of gold nanorods.

PMID- 18348157
TI  - Automated solid-phase synthesis of protected oligosaccharides containing beta
      mannosidic linkages.
AB  - For automated oligosaccharide synthesis to impact glycobiology, synthetic access
      to most carbohydrates has to become efficient and routine. Methods to install
      "difficult" glycosidic linkages have to be established and incorporated into the
      overall synthetic concept. Described here is the first automated solid-phase
      synthesis of oligosaccharides containing the challenging beta-mannosidic linkage.
      Carboxybenzyl mannoside building blocks proved effective beta-mannosylation
      agents and resulted in excellent conversion and good to moderate selectivities.
      [(Triisopropylsilyl)oxy]-methyl ether (Tom), served as an orthogonal, minimally
      intrusive, and readily cleavable protecting group for the elongation of the C3
      position of mannose. The desired oligosaccharide products were readily separated
      from by-products containing unwanted stereoisomers using reverse-phase HPLC. The
      methods described here expand the scope of carbohydrates currently accessible by
      automation as many oligosaccharides of biological interest contain beta
      mannosidic linkages.

PMID- 18348158
TI  - Genetic caste determination in termites: out of the shade but not from Mars.
AB  - Several ant species are known with genetic effects on caste determination but,
      for termites, the role of environment has been assumed to be omnipotent. Now
      Hayashi et al. report that commitment to the nymph and worker pathways in
      Reticulitermes speratus follows a simple model involving two alleles at a sex
      linked locus. The spread of this system of genetic caste determination seems best
      explained by selection at the colony level. This remarkable system may be widely
      applicable throughout termites, although it cannot be universal, and may provide
      a window into causal aspects of the molecular biology of caste determination.

PMID- 18348159
TI  - miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres
      characterized by low miR-150 and high BIC/miR-155 expression.
AB  - Several miRNAs have been reported to be associated with immunoglobulin heavy
      chain (IgH) mutation and ZAP-70 expression status in blood samples of B-cell
      chronic lymphocytic leukaemia/small lymphocytic lymphoma (B-CLL/SLL). In the bone
      marrow and lymphoid tissues, proliferation centres (PCs) represent an important
      site of activation and proliferation of the neoplastic cells, suggesting that
      these tissues better reflect the biology of CLL than circulating blood cells. We
      collected 33 lymph nodes and 37 blood CLL samples and analysed IgH mutation
      status and ZAP-70 expression status. Expression of 15 miRNAs was analysed by qRT
      PCR and RNA-ISH. Sixty-three per cent of the lymph node cases contained mutated
      IgH genes and 49% of the lymph node cases were ZAP-70-positive, and a significant
      correlation was observed between ZAP-70 expression and IgH mutation status. Of
      the blood CLL samples, 49% contained mutated IgH sequences. The miRNA expression
      pattern in CLL lymph node and blood samples was very similar. Three of 15 miRNAs
      (miR-16, miR-21, and miR-150) showed a high expression level in both blood and
      lymph node samples. No difference was observed between ZAP-70-positive or 
      negative and between IgH-mutated or unmutated cases. No correlation was found
      between miR-15a and miR-16 expression levels and 13q14 deletion in the blood CLL
      samples. RNA in situ hybridization (ISH) revealed strong homogeneous staining of
      miR-150 in the tumour cells outside the PCs. In reverse BIC/pri-miR-155
      expression was observed mainly in individual cells including prolymphocytes of
      the PCs. This reciprocal pattern likely reflects the different functions and
      targets of miR-150 and miR-155.

PMID- 18348160
TI  - Differential expression of SOX17 and SOX2 in germ cells and stem cells has
      biological and clinical implications.
AB  - Combined action of SOX and POU families of transcription factors plays major
      roles in embryonic development. In embryonic stem cells, the combination of SOX2
      and POU5F1 (OCT3/4) is essential for maintaining the undifferentiated state by
      activating pluripotency-linked genes, and inhibition of genes involved in
      differentiation. Besides embryonic stem cells, POU5F1 is also present in early
      germ cells, primordial germ cells, and gonocytes, where it has a role in
      suppression of apoptosis. Here we demonstrate that SOX2 is absent in germ cells
      of human fetal gonads, and as expected carcinoma in situ (CIS), ie the precursor
      lesion of testicular germ cell tumours of adolescents and adults (TGCTs), and
      seminoma. Based on genome-wide expression profiling, SOX17 was found to be
      present, instead of SOX2, in early germ cells and their malignant counterparts,
      CIS and seminoma. Immunohistochemistry, western blot analysis, and quantitative
      RT-PCR showed that SOX17 is a suitable marker to distinguish seminoma from
      embryonal carcinoma, confirmed in representative cell lines. Aberrant SOX2
      expression can be present in Sertoli cells when associated with CIS, which can be
      misdiagnosed as embryonal carcinoma. In conclusion, this study demonstrates the
      absence of SOX2 in human embryonic and malignant germ cells, which express SOX17
      in conjunction with POU5F1. This finding has both diagnostic and developmental
      biological implications. It allows the identification of seminoma-like cells from
      embryonal carcinoma based on a positive marker and might be the explanation for
      the different function of POU5F1 in normal and malignant germ cells versus
      embryonic stem cells.

PMID- 18348161
TI  - Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium
      in longstanding ileal Crohn's disease.
AB  - In Crohn's disease (CD), inflammation is driven by luminal commensal micro
      organisms; however, mechanisms of early phases of inflammation need further
      clarification. The earliest observable lesions of recurrent CD are microscopic
      erosions at the specialized follicle-associated epithelium (FAE), which lines the
      Peyer's patches. Therefore, our aim was to investigate the mucosal barrier to non
      pathogenic bacteria in FAE of CD. The FAE of macroscopically normal ileum from
      patients with longstanding CD, ulcerative colitis, and controls was studied in
      Ussing chambers regarding electrophysiology and permeability to 51Cr-EDTA,
      horseradish peroxidase, and non-pathogenic E. coli strains. Transepithelial
      passage routes and uptake into dendritic cells were studied by confocal and
      electron microscopy. FAE of CD showed increased numbers of adherent bacteria,
      after E. coli exposure in Ussing chambers, as well as spontaneously in non
      exposed archival surgical tissues. Further, we found increased uptake of
      fluorescent E. coli K-12 and HB101 across FAE of CD, but not in ulcerative
      colitis. Microscopy demonstrated intercellular and transcellular uptake of E.
      coli in CD, but only transcellular in controls. FAE exposed to E. coli
      demonstrated changes in conductance and 51Cr-EDTA permeability, suggesting that
      bacteria affected the paracellular pathway in CD mucosa. Following bacterial
      uptake, CD mucosa also demonstrated an increased percentage of E. coli co
      localizing with dendritic cells, and augmented tissue release of TNF-alpha. Our
      data present novel insights into the pathophysiology of CD by demonstrating a
      previously unrecognized defect of FAE barrier to bacteria in ileal CD, leading to
      increased load of commensal bacteria to the inductive sites of mucosal immunity.

PMID- 18348162
TI  - FOXL2 and SOX9 as parameters of female and male gonadal differentiation in
      patients with various forms of disorders of sex development (DSD).
AB  - The transcription factors SOX9 and FOXL2 are required for male and female
      mammalian gonadal development. We have used specific antibodies to investigate
      the role of these key proteins in disorders of sex development (DSD),
      specifically inter-sex states. In normal gonads, SOX9 was found to be restricted
      to the presence of (pre-)Sertoli cells, while FOXL2 was found in granulosa cells,
      and in stromal cells interpreted as early ovarian stroma. Both proteins were
      found within a single patient, when testicular and ovarian development was
      present; and within the same gonad, when both differentiation lineages were
      identified, as in ovotesticular DSD (ie hermaphrodite). Especially SOX9 was
      informative to support the presence of early testicular development (ie
      seminiferous tubules), expected based on morphological criteria only. In a
      limited number of DSD cases, FOXL2 was found within reasonably well-developed
      seminiferous tubules, but double staining demonstrated that it was never strongly
      co-expressed with SOX9 in the same cell. All seminiferous tubules containing
      carcinoma in situ (CIS), the malignant counterpart of a primordial germ cell, ie
      the precursor of type II germ cell tumours of the testis, seminomas and non
      seminomas, showed the presence of SOX9 and not FOXL2. In contrast,
      gonadoblastomas (GBs), the precursor of the same type of cancer, in a dysgenetic
      gonad, showed expression of FOXL2 and no, or only very low, SOX9 expression.
      These findings indicate that gonadal differentiation, ie testicular or ovarian,
      determines the morphology of the precursor of type II germ cell tumours, CIS or
      GB, respectively. We show that in DSD patients, the formation of either ovarian
      or/and testicular development can be visualized using FOXL2 and SOX9 expression,
      respectively. In addition, it initiates a novel way to study the role of the
      supportive cells in the development of either CIS or GB.

PMID- 18348163
TI  - JNK modulates the effect of caspases and NF-kappaB in the TNF-alpha-induced down
      regulation of Na+/K+ATPase in HepG2 cells.
AB  - An inhibition of the Na(+)/K(+)ATPase was previously shown to accompany and
      potentiate apoptosis in different experimental models. Since TNF-alpha is known
      to be a pro and anti-apoptotic cytokine, this work was undertaken to study the
      effect of TNF-alpha on the Na(+)/K(+)ATPase in HepG2 cells and to determine the
      signaling pathway involved. Cells were incubated for 1 h with TNF-alpha in
      presence and absence of PDTC, SP600125 and FK009, respective inhibitors of NF-KB,
      c-JNK, and caspases. The activity of the pump was assayed by measuring the
      ouabain-inhibitable release of inorganic phosphate, and changes in its expression
      were monitored by western blot analysis. TNF-alpha decreased significantly the
      activity and protein expression of the Na(+)/K(+)ATPase. NF-kappaB and caspases
      were found to be the main effectors of the cytokine, mediating respectively down
      regulation and up-regulation of the pump. Their activity was however modulated at
      1 h by c-JNK, which stimulated the caspases and inhibited NF-kappaB, resulting in
      a net inhibition of the ATPase, and probably favoring the apoptotic pathway.

PMID- 18348164
TI  - Effect of [Cl(-)]i on ENaC activity from mouse cortical collecting duct cells.
AB  - Na(+) transport via epithelial Na(+) channel (ENaC) occurs across many epithelial
      surfaces and plays a key role in regulating salt and water absorption. In this
      study, we have examined the effects of cytosolic Na(+) and Cl(-) on ENaC activity
      by patch clamping single channel recording method in mouse cortical collecting
      duct cells (M1). Cytosolic Na(+) exerts its effect in change of ENaC open
      probability (Po). High cytosolic Na(+) significantly reduces ENaC Po. No change
      in channel conductance by cytosolic Na(+) is observed. However, decrease of
      cytosolic Cl(-) concentration significantly increases channel conductance and
      ENaC Po. This effect is due to the right shift of ENaC I-V curve to positive
      membrane potential. The virtue of ENaC conductance remains the same. Cl(-)
      channels like CFTR and VRAC are unlikely to be involved in this regulation. The
      results suggest that cytosolic Cl(-) could serve as a mediator to regulate ENaC
      activity, in accordance with the activities of Cl(-) channels.

PMID- 18348165
TI  - DNA damage, RAD9 and fertility/infertility of Echinococcus granulosus hydatid
      cysts.
AB  - Hydatidosis, caused by the larval stage of the platyhelminth parasite
      Echinococcus granulosus, affects human and animal health. Hydatid fertile cysts
      are formed in intermediate hosts (human and herbivores) producing protoscoleces,
      the infective form to canines, at their germinal layers. Infertile cysts are also
      formed, but they are unable to produce protoscoleces. The molecular mechanisms
      involved in hydatid cysts fertility/infertility are unknown. Nevertheless,
      previous work from our laboratory has suggested that apoptosis is involved in
      hydatid cyst infertility and death. On the other hand, fertile hydatid cysts can
      resist oxidative damage due to reactive oxygen and nitrogen species. On these
      foundations, we have postulated that when oxidative damage of DNA in the germinal
      layers exceeds the capability of DNA repair mechanisms, apoptosis is triggered
      and hydatid cysts infertility occurs. We describe a much higher percentage of
      nuclei with oxidative DNA damage in dead protoscoleces and in the germinal layer
      of infertile cysts than in fertile cysts, suggesting that DNA repair mechanisms
      are active in fertile cysts. rad9, a conserved gene, plays a key role in cell
      cycle checkpoint modulation and DNA repair. We found that RAD9 of E. granulosus
      (EgRAD9) is expressed at the mRNA and protein levels. As it was found in other
      eukaryotes, EgRAD9 is hyperphosphorylated in response to DNA damage. Our results
      suggest that molecules involved in DNA repair in the germinal layer of fertile
      hydatid cysts and in protoscoleces, such as EgRAD9, may allow preserving the
      fertility of hydatid cysts in the presence of ROS and RNS.

PMID- 18348166
TI  - Adenovirus E1A oncoprotein liberates c-Myc activity to promote cell proliferation
      through abating Bin1 expression via an Rb/E2F1-dependent mechanism.
AB  - Adenovirus E1A oncogene transforms primary rodent fibroblasts in cooperation with
      activated Ras. Conversely, the c-Myc oncoprotein-binding tumor suppressor, Bin1,
      inhibits Ras/E1A-mediated cell transformation. Since E1A does not directly bind
      to and inhibit Bin1, the primary mechanism by which E1A counteracts Bin1 to
      liberate oncogenic c-Myc activity is poorly understood. Here we show that wild
      type E1A, but not an Rb binding-defective E1A mutant, suppresses endogenous Bin1
      expression in cultured rodent fibroblasts. Similarly, other anti-Rb agents, such
      as human papillomavirus E7, mitogenic stimuli, and small interfering RNA (siRNA)
      for Rb, consistently decrease Bin1 promoter activity. In contrast, serum
      starvation, which activates Rb, enhances endogenous Bin1 levels. These findings
      suggest that Bin1 may be a novel component of Rb-mediated G1 arrest. Consistent
      with this premise, chromatin immunoprecipitation assays demonstrate that Rb
      protein directly interacts with the Bin1 promoter only upon removal of serum.
      Furthermore, ectopically expressed E2F1, which is primarily inhibited by Rb under
      serum-starved condition, represses Bin1 promoter activity in a manner that is
      dependent on the DNA-binding and transactivation domains of E2F1. Lastly,
      depletion of endogenous Bin1 per se is biologically meaningful since antisense or
      siRNA of Bin1 transfection releases endogenous c-Myc transcriptional activity
      and, concomitantly, accelerates cell proliferation. Our results suggest that Bin1
      gene suppression caused by oncogenic E1A via Rb inactivation is an essential step
      in cell cycle progression promoted by c-Myc, and subsequently, E1A
      transformation. We propose a novel G1 arrest signaling mechanism by which Rb
      indirectly curbs oncogenic c-Myc activity via sustaining Bin1 expression.

PMID- 18348167
TI  - Non-enzymatic glycation of type I collagen diminishes collagen-proteoglycan
      binding and weakens cell adhesion.
AB  - Non-enzymatic glycation of type I collagen occurs in aging and diabetes, and may
      affect collagen solubility, charge, polymerization, and intermolecular
      interactions. Proteoglycans(1) (PGs) bind type I collagen and are proposed to
      regulate fibril assembly, function, and cell-collagen interactions. Moreover, on
      the collagen fibril a keratan sulfate (KS) PG binding region overlaps with
      preferred collagen glycation sites. Thus, we examined the effect of collagen
      modified by simple glycation on PG-collagen interactions. By affinity
      coelectrophoresis (ACE), we found reduced affinities of heparin and KSPGs for
      glycated but not normal collagen, whereas the dermatan sulfate (DS)PGs decorin
      and biglycan bound similarly to both, and that the affinity of heparin for normal
      collagen decreased with increasing pH. Circular dichroism (CD) spectroscopy
      revealed normal and glycated collagens to assume triple helical conformations,
      but heparin addition caused precipitation and decreased triple helical content
      effects that were more marked with glycated collagen. A spectrophotometric assay
      revealed slower polymerization of glycated collagen. However, ultrastructural
      analyses indicated that fibrils assembled from normal and glycated collagen
      exhibited normal periodicity, and had similar structures and comparable diameter
      distributions. B-cells expressing the cell surface heparan sulfate PG syndecan-1
      adhered well to normal but not glycated collagen, and endothelial cell migration
      was delayed on glycated collagen. We speculate that glycation diminishes the
      electrostatic interactions between type I collagen and PGs, and may interfere
      with core protein-collagen associations for KSPGs but not DSPGs. Therefore in
      vivo, collagen glycation may weaken PG-collagen interactions, thereby disrupting
      matrix integrity and cell-collagen interactions, adhesion, and migration.

PMID- 18348168
TI  - Selective antiaggressive effect of an alpha-2 adrenoceptor agonist
      naphthylmedetomidine in mice.
AB  - Alpha-2 adrenoceptors (alpha(2)-ARs) are critically involved in regulating
      neurotransmitter release from sympathetic nerves and neurons and play an
      important role in the regulation of awareness, arousal and vigilance. In our
      recent study, dexmedetomidine, a full alpha(2)-AR agonist, produced
      antiaggressive effects in the social conflict test in mice at doses that were
      twice smaller than those producing sedation. The aim of this study was to
      ascertain antiaggressive effect of a novel drug naphthylmedetomidine, with a more
      selective alpha(2)-AR activity. Behavioral effects of naphthylmedetomidine (150
      1200 microg/kg i.p.) were studied in the activity cage and in the social conflict
      tests in mice. Naphthylmedetomidine dose dependently decreased aggressive
      behavior during social conflict in aggressive mice with significant reduction
      already at the lowest doses tested (150 microg/kg), whereas locomotion and social
      investigation were significantly decreased only after four times bigger dose of
      naphthylmedetomidine (600 microg/kg) in aggressive mice. Naphthylmedetomidine had
      no effect on aggression in nonaggressive mice. Naphthylmedetomidine reduced
      locomotion in the activity cage significantly only at the highest doses tested
      (600 and 1200 microg/kg), and this effect was only partially reversed by
      administration of high doses of an alpha-2 antagonist atipamezole (3 and 10
      mg/kg). In nonaggressive mice, the difference between the dose reducing dominant
      social behavior (social investigation) and locomotion (150 and 300 microg/kg,
      respectively) was smaller than in aggressive mice. In conclusion,
      naphthylmedetomidine showed a very strong and selective antiaggressive effect in
      aggressive mice, which was devoid of locomotion-inhibiting/sedative effect. This
      study suggests that naphthylmedetomidine may have clinical potential as
      antiaggressive drug.

PMID- 18348169
TI  - What can variation in stature reveal about environmental differences between
      prehistoric Jomon foragers? Understanding the impact of systemic stress on
      developmental stability.
AB  - This study reconstructs patterns of stress and phenotypic variation in
      prehistoric Japan. Greater evidence for stress is indicated by elevated enamel
      hypoplasia frequency among Jomon foragers from western compared to eastern Japan.
      Geographic variation in stress between Jomon people is related to plant-based
      diets and resource scarcity in western Japan. The hypothesis that Jomon people
      from western Japan had shorter stature than those from the east is, therefore,
      tested. Relationships between individual stature, geographic location, and enamel
      hypoplasia presence/absence are also explored. In addition, increased population
      density and reliance on plant foods are observed during the Late/Final Jomon
      period in western Japan. A second hypothesis proposing shorter stature for
      Late/Final Jomon people compared to those from the Middle Jomon period is tested.
      Statistically significant differences in stature between males and females from
      eastern and western Japan were not observed. Individual relationships between
      enamel hypoplasia and stature were rejected. Stature decreased significantly over
      time in western Japan. It is possible that stature between the eastern and
      western Jomon did not differ because the western Jomon experienced catch up
      growth after childhood stress episodes. It is also likely that variation in
      stress between the two groups was not severe enough to warrant stature reduction.
      Decreases in stature through time in western Japan are related to increased
      exposure to chronic infection and dietary stress. Overall, these results indicate
      that enamel hypoplasia frequencies provide an adequate index of general stress
      but may fail to predict the impact of stress on the human phenotype.

PMID- 18348170
TI  - Rural urban differences of cardiovascular disease risk factors in adult Asian
      Indians.
AB  - The prevalence of cardiovascular disease (CVD) risk factors in "People of Indian
      Origin" (PIO) is exceedingly high and strong relationships among elevated blood
      pressure, increased levels of lipoproteins, visceral obesity, physical inactivity
      and subsequent high occurrence of coronary heart disease, type 2 diabetes
      mellitus etc., were evident in many studies. Increasing urbanization with
      effective changes in lifestyles could be attributed to explain this exaggerated
      rate. The present community based cross-sectional investigation was aimed to
      identify rural-urban differences in prevalence of risk factors of CVD in the
      adult Asian Indians. A total of 350 adult (30 years and above) individuals (184
      males and 166 females) belong to urban (n = 193, males = 104, and females = 89)
      and rural (n = 157, males = 80, and females = 77) areas participated in the
      study. Anthropometric measures, lipids profiles, fasting blood glucose and blood
      pressure measures were obtained from participants. The mean body mass index
      (kg/m2) for male and female was 22.37 +/- 4.09 and 23.20 +/- 4.37, respectively.
      There existed significant differences for anthropometric, metabolic, and blood
      pressure variables between rural and urban areas. Habitat (rural vs. urban) had
      significant impact on central adiposity, lipids, lipoproteins, and blood pressure
      measures even after adjusted for age and sex. Overall, 84.3% of females had lower
      HDL level compared with only 20.1% in males. It was also observed that the
      prevalence of metabolic syndrome was 56.2% in urban females compared with 36.4%
      in rural females. Effective urbanization and or modernization seem to influence
      CVD risk factors and warrants intervention as early as adulthood to check this
      menace.

PMID- 18348171
TI  - Relation of ratio indices of anthropometric measures to obesity in a stunted
      population.
AB  - The ratios of anthropometric measures are used to estimate obesity while
      controlling for allometric scaling. A good index should be uncorrelated with its
      denominator; this often requires exponentiation of the denominator. The stability
      of the derived exponents across populations is not known. We obtained subscapular
      (SUBS) and triceps (TRI) skinfolds, weight (WT), height (HT), waist circumference
      (WC), fat mass (FM), and fat-free mass (FFM) in a population of Guatemalan adults
      [height 1.63 +/- 0.06 m (868 males); 1.51 +/- 0.06 m (1047 females)]. We derived
      exponents for the indices WT/HT(P), SUBS/TRI(P), TRI/SUBS(P), WC/HT(P), FM/WT(P),
      and FM/FFM(P) such that the ratios were free from association with their
      denominators. The derived exponents were (Men: SUBS/TRI(0.88), FM/WT(2.69),
      FM/FFM(2.86), WC/HT(0.68), and WT/HT(2.17); Women: SUBS/TRI(0.93), FM/WT(2.01),
      FM/FFM(3.37), WC/HT(0.47), WT/HT(2.03)). For all examined indices the derived
      exponents differed (P < 0.05) from 1 and differed (P < 0.05) between men and
      women. The exponents for the men also differed from those previously published
      for Brazilian men (JCK Wells and CG Victora [2005]: Int J Obes 29:483-489). The
      derived indices were not more strongly correlated with adiposity than were simple
      unexponentiated ratios. Although exponentiation of the denominator eliminates the
      association of index with its denominator, the resulting exponents lack
      generalizability across populations, especially those where stunting remains
      prevalent.

PMID- 18348172
TI  - Low digit ratio (2D:4D) is associated with delayed menarche.
AB  - The prenatal environment of the human fetus is now known to have lasting
      physiological and behavioral effects into childhood and adulthood. The objective
      of this study was to examine the relationship between early testosterone
      exposure, as measured by the ratio of the length of the 2nd and 4th digits (2D:4D
      ratio), and age of menarche. Retrospective, self-report data on menarcheal age
      were obtained from 206 healthy female college students, as well as finger length
      ratio data from both hands. Low right-hand 2D:4D ratios (but not left-hand) were
      associated with delayed menarche. The results provide evidence for an androgen
      delayed menarche link and suggest that this relationship can be continuous in
      nature and not always categorical as occurs in congenital adrenal hyperplasia,
      hyperandrogenism, or polycystic ovary syndrome.

PMID- 18348173
TI  - Energy expenditure among farmers in developing countries: what do we know?
AB  - The trend toward overweight and obesity in developing countries is often assumed
      to be due, in part, to reductions in energy expenditure associated with the
      transition from agrarian to urban lifestyles. In this article we first review the
      published studies on energy expenditure in farming populations living in
      developing countries, populations generally assumed to have high levels of energy
      expenditure. To facilitate comparison we express energy expenditure as physical
      activity level (PAL), i.e. the ratio of total daily energy expenditure to basal
      metabolic rate. Then, with the goal of better understanding variability in energy
      expenditure between different human groups, we focus on case studies of women
      farmers in Colombia and Brazil for whom we have good ethnographic data. The
      published studies reviewed indicate that most farmers have PAL values in the
      moderate physical activity range, but toward the high end of that range. PAL
      values of male farmers tend to be higher than female, and show greater seasonal
      variation. The case studies illustrate that women farmers, living in broadly
      similar environments, and dependent on the cultivation of the same crop can have
      quite different patterns of physical activity and hence PAL values. These
      differences are a function of differences in behavior related to social and
      cultural variables like the organization of work at the household level and
      perceptions of how food crops should be processed, as well as micro-level
      ecological factors.

PMID- 18348174
TI  - Developmental changes in the relationship between leptin and adiposity among
      Tsimane children and adolescents.
AB  - Leptin is thought to signal energy stores, thus helping the body balance energy
      intake and expenditure. However, the strong relationship between leptin and
      adiposity in populations with adequate nutrition or common obesity is not
      universal across ecologic contexts, and leptin often correlates only weakly, or
      not at all, with adiposity in populations of lean or marginally-nourished males.
      To clarify whether the relationship between adiposity and leptin changes during
      development, this study examines leptin and body fat among children and
      adolescents of lowland Bolivia. Anthropometric measures of body composition and
      dried blood spot samples were collected from 487 Tsimane' ranging from 2 to 15
      years of age. Leptin was assayed using an enzyme immunoassay protocol validated
      for use with blood spot samples. In this population, leptin concentrations were
      among the lowest reported in a human population (mean +/- SD: 1.26 +/- 0.5 and
      0.57 +/- 0.3 in females and males). In addition, the relationship between leptin
      and adiposity follows distinct developmental trajectories in males and females.
      In males, leptin is weakly correlated with most measures of body composition at
      all ages investigated. However, in females, the level of body fat and the
      strength of the correlation between body fat and leptin (a measure of its
      strength as a signal of energy stores) both increase markedly with age. These
      findings suggest a more important role of leptin as a signal of energy stores
      among females as they approach reproductive maturity, while raising questions
      about the function of this hormone in lean males.

PMID- 18348175
TI  - Silicon nanotechnologies of pigmented heterokonts.
AB  - Many pigmented heterokonts are able to synthesize elements of their cell walls
      (the frustules) of dense biogenic silica. These include diatom algae, which
      occupy a significant place in the biosphere. The siliceous frustules of diatoms
      have species-specific patterns of surface structures between 10 and a few hundred
      nanometers. The present review considers possible mechanisms of uptake of silicic
      acid from the aquatic environment, its transport across the plasmalemma, and
      intracellular transport and deposition of silica inside the specialized Silica
      Deposition Vesicle (SDV) where elements of the new frustule are formed. It is
      proposed that a complex of silicic acid with positively charged proteins
      silaffins and polypropylamines remains a homogeneous solution during the
      intracellular transport to SDV, where biogenic silica precipitates. The high
      density of the deposited biogenic silica may be due to removal of water from the
      SDV by aquaporins followed by syneresis--a process during which pore water is
      expelled from the network of the contracting gel. The pattern of aquaporins in
      the silicalemma, the membrane embracing the SDV, can determine the pattern of
      species-specific siliceous nanostructures.

PMID- 18348176
TI  - BimEL-dependent apoptosis induced in peripheral blood lymphocytes with n-butyric
      acid is moderated by variation in expression of c-myc and p21(WAF1).
AB  - We have examined the effect of sodium butyrate (SB) on the viability of normal
      peripheral blood lymphocytes (PBLs) in vitro and the effect of this agent on the
      expression of 20 apoptosis-related genes. Data suggest that PBL treated with 2
      mmol L(-1) SB resisted for at least 8 h the destructive activity of the agent,
      but eventually 30% of cells died within 72 h. As documented by flow cytometry and
      cytochrome c release study, cells underwent mitochondrial-derived apoptosis.
      While the expression of the majority of genes examined by RT-PCR and Western
      blots remained indifferent to 2 mmol L(-1) SB, the cellular levels of BimEL, c
      myc, p53, and p21(WAF1) varied profoundly with the time of SB treatment. The Bax
      activator BimEL increased rapidly, driving cells toward apoptosis likely
      controlled by c-myc and p21(WAF1) activities. The c-myc, exercising the role of
      mediator of the function of BimEL and inhibitor of p21(WAF1) expression,
      decreased significantly for several hours after adding SB but within 48 h it
      returned to close to its original value. An apoptosis inhibitor and executive
      caspase substrate p21(WAF1) increased early at the beginning of treatment but
      subsequently, within a time frame of 72 h, profoundly dropped in terms of both a
      caspase-dependent and caspase-independent way. We suggest that variations in c
      myc and p21(WAF1) expression delay apoptosis making PBL resistant to SB for
      several hours, and together with fast catabolism of SB in vivo protect PBL
      against the destructive activity of this anti-cancerous metabolite of colonic
      bacteria.

PMID- 18348177
TI  - Characterization of RNA-binding proteins possibly involved in modulating human AT
      1 receptor mRNA stability.
AB  - Angiotensin II exerts its cardiovascular effects mainly through the activation of
      AT(1) receptors. These receptors can be regulated at a post-transcriptional
      level, that is through the modulation of the mRNA stability. This regulation
      usually involves proteins which are able to bind the 3'UTR of the mRNA molecule.
      The experiments of the present paper were performed in order to characterize the
      RNA-binding proteins interacting with the hAT(1) receptor mRNA in human vascular
      smooth muscle cells. Immunoblot analysis allowed us to identify three different
      RNA-binding proteins, AUF1, HuR, and hnRNP A1. UV cross-linking and
      immunoprecipitation experiments demonstrated that AUF1 binds to the hAT(1)
      receptor mRNA radiolabeled probes specifically, but in different ways in relation
      to the clinically important A/C gene polymorphism. Gel shift experiments using
      purified recombinant proteins confirmed the specificity of interaction of these
      proteins with the hAT(1)-receptor mRNA. In basal conditions the proteins were
      mainly located in the nuclei, but angiotensin II administration clearly induced
      their translocation to the cytosol. This observation was confirmed by
      transfection experiments using both GFP/AUF1 and GFP/HuR fusion proteins. Our
      findings allow identification of specific RNA-binding proteins possibly involved
      in the control of the hAT1-receptor mRNA stability and in the regulation of their
      expressions.

PMID- 18348178
TI  - Changes in calcium-dependent membrane permeability properties in mitochondria of
      livers from arthritic rats.
AB  - The involvement of the mitochondrial permeability transition pore (PTP) in the
      responses of mitochondria from adjuvant-induced arthritic rats to Ca(2+) addition
      was investigated. The respiratory activity, the Ca(2+)-induced osmotic swelling
      and the electrophoretic (45)Ca(2+) uptake were evaluated in the absence and in
      the presence of cyclosporin A (CsA), a well-known inhibitor of the mitochondrial
      PTP. The Ca(2+)-induced mitochondrial permeability transition (MPT) process
      occurred in mitochondria from arthritic rats even in the presence of a low Ca(2+)
      concentration. Whereas in the normal condition, the Ca(2+)-induced uncoupling of
      oxidative phosphorylation and osmotic swelling was observed in the presence of 10
      or 20 microM Ca(2+) concentration, in the arthritic condition, these events
      occurred at 1.0 microM concentration. In addition, mitochondria from arthritic
      rats presented an impaired ability to accumulate (45)Ca(2+). All these effects
      were completely prevented by the administration of CsA. The results of the
      present study suggest that the higher sensitivity of mitochondria from arthritic
      rats to Ca(2+)-induced MPT may be an important factor in the pathogenesis of the
      arthritis disease.

PMID- 18348179
TI  - The "street light syndrome", or how protein taxonomy can bias experimental
      manipulations.
AB  - In the genomics era, bioinformatic analysis, especially in non-model species,
      facilitates the identification and naming of numerous new proteins, the function
      of which is then inferred through homology searches. Here, we question certain
      aspects of these approaches. What are the criteria that permit such a
      determination? What are their limits? Naming is classifying. We review the
      different criteria that are used to name a protein and discuss their constraints.
      We observe that the name given to a protein often introduces a bias for further
      functional analyses, a bias that is not often taken into account when analysing
      results. Last but not least, the heterogeneity of criteria used for naming
      proteins leads to self-inconsistent or contradictory protein classification that
      is potentially misleading. Finally, we recommend a wider use of phylogenetic
      criteria in protein naming.

PMID- 18348180
TI  - The effects of rosiglitazone on oxidative stress and lipid profile in left
      ventricular muscles of diabetic rats.
AB  - We investigated the effect of rosiglitazone (RSG), a high-affinity ligand for the
      peroxisome proliferator-activated receptor gamma which mediates insulin
      sensitizing actions, on the lipid profile and oxidative status in streptozotocin
      (STZ)-induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were
      randomly divided into an untreated control group (C), a C + RSG group which was
      treated with RSG (4 mg kg(-1)) two times a day by gavage, a diabetic group (D)
      that was treated with a single intraperitoneal injection of STZ (45 mgkg(-1)), D
      + RSG group which were treated with RSG two times a day by gavage, respectively.
      Lipid profiles, HbA(1c) and blood glucose levels in the circulation and
      malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in left ventricular
      muscle were measured. Treatment of D rats with RSG resulted in a time-dependent
      decrease in blood glucose. We found that the lipid profile and HbA(1c) levels in
      D + RSG group reached the C rat values at the end of the treatment period. There
      was a statistically significant difference between the C + RSG and C groups in 3
      NT levels. In group D, 3-NT and MDA levels were found to be increased when
      compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels
      were found to be decreased when compared with C and C + RSG. Our study suggests
      that the treatment of D rats with RSG for 8 weeks may decrease the
      oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes
      related vascular diseases, RSG treatment may be cardioprotective.

PMID- 18348181
TI  - Development of the VBLaST: a virtual basic laparoscopic skill trainer.
AB  - BACKGROUND: The FLS training tool box has now been adopted by the Society of
      Gastrointestinal Endoscopic Surgeons (SAGES) as an official training tool for
      minimally invasive procedures. METHODS: To overcome the limitations of the
      physical FLS training tool box, we have developed a Virtual Basic Laparoscopic
      Skill Trainer (VBLaSTTM) system, which is a 3D simulator that will allow trainees
      to acquire basic laparoscopic skill. RESULTS: The outcome of this work is the
      development of an integrated visio-haptic workstation environment including force
      feedback devices and a stereo display interface whereby trainees can practice on
      virtual versions of the FLS. Realistic graphical rendering and high fidelity
      haptic interactions are achieved. CONCLUSIONS: Surgical skill training is a long
      and tedious process of acquiring fine motor skills. It is expected that residents
      would start on trainers such as VBLaSTTM and after reaching a certain level of
      competence would progress to the more complex trainers for training on specific
      surgical procedures.

PMID- 18348182
TI  - Computer-assisted implantology: historical background and potential outcomes-a
      review.
AB  - BACKGROUND: The accurate transfer of preoperatively determined implant positions
      to the patient mouth is very beneficial to the dental practitioner as well as
      patients. The objective of this paper was to review the gradual development of
      computer-assisted implant surgery. METHODS: All of the major data sources
      including unpublished data in the internet are considered RESULTS AND
      CONCLUSIONS: Computer-assisted/-guided/-aided implantology has been founded to
      overcome the errors encountered during implant osteotomies and to position the
      implants more precisely. The protocols followed by this sophisticated technique
      are based upon the advocated concept of prosthetic-driven implantology and CT
      scan analysis recently approved. Although several attempts have been made to
      improve this approach more and more, little has been done regarding the patient's
      demands, including cost. The inherent complexity of the techniques and materials
      utilized necessitates several degrees of training before attempting treatment and
      must be taken into account.

PMID- 18348183
TI  - New charts for ultrasound dating of pregnancy and assessment of fetal growth:
      longitudinal data from a population-based cohort study.
AB  - OBJECTIVES: Correct assessment of gestational age and fetal growth is essential
      for optimal obstetric management. The objectives of this study were, first, to
      develop charts for ultrasound dating of pregnancy based on crown-rump length and
      biparietal diameter and, second, to derive reference curves for normal fetal
      growth based on biparietal diameter, head circumference, transverse cerebellar
      diameter, abdominal circumference and femur length from 10 weeks of gestational
      age onwards. METHODS: A total of 8313 pregnant women were included for analysis
      in this population-based prospective cohort study. All women had repeated
      ultrasound assessments to examine fetal growth. RESULTS: Charts for ultrasound
      dating of pregnancy, based on crown-rump length and biparietal diameter, were
      derived. Internal validation with the actual date of delivery showed that
      ultrasound imaging provided reliable gestational age estimates. Up to 92% of
      deliveries took place within 37-42 weeks of gestation if gestational age was
      derived from ultrasound data, compared with 87% based on a reliable last
      menstrual period. The earlier the ultrasound assessment the more accurate the
      prediction of date of delivery. After 24 weeks of gestation a reliable last
      menstrual period provided better estimates of gestational age. Reference curves
      for normal fetal growth from 10 weeks of gestational age onwards were derived.
      CONCLUSIONS: Charts for ultrasound dating of pregnancy and reference curves for
      fetal biometry are presented. The results indicate that, up to 24 weeks of
      pregnancy, dating by ultrasound examination provides a better prediction of the
      date of delivery than does last menstrual period. The earlier the ultrasound
      assessment in pregnancy, preferably between 10 and 12 weeks, the better the
      estimate of gestational age.

PMID- 18348184
TI  - Gene duplications, robustness and evolutionary innovations.
AB  - Mutational robustness facilitates evolutionary innovations. Gene duplications are
      unique kinds of mutations, in that they generally increase such robustness. The
      frequent association of gene duplications in regulatory networks with
      evolutionary innovation is thus a special case of a general mechanism linking
      innovation to robustness. The potential power of this mechanism to promote
      evolutionary innovations on large time scales is illustrated here with several
      examples. These include the role of gene duplications in the vertebrate
      radiation, flowering plant evolution and heart development, which encompass some
      of the most striking innovations in the evolution of life.

PMID- 18348185
TI  - Expression and localization of estrogen receptor alpha in the C2C12 murine
      skeletal muscle cell line.
AB  - The classical model of 17beta-estradiol action has been traditionally described
      to be mediated by the estrogen receptor (ER) localized exclusively in the
      nucleus. However, there is increasing functional evidence for extra nuclear
      localization of ER. We present biochemical, immunological and molecular data
      supporting mitochondrial-microsomal localization of ER alpha in the C2C12
      skeletal muscle cell line. We first established [(3)H]17beta estradiol binding
      characteristics in whole cells in culture. Specific and saturable [(3)H]17beta
      estradiol binding sites of high affinity were then detected in mitochondrial
      fractions (K(d) = 0.43 nM; B(max) = 572 fmol/mg protein). Immunocytological
      studies revealed that estrogen receptors mainly localize at the mitochondrial and
      perinuclear level. These results were also confirmed using fluorescent 17beta
      estradiol-BSA conjugates. The immunoreactivity did not translocate into the
      nucleus by 17beta-estradiol treatment. Western and Ligand blot approaches
      corroborated the non-classical localization. Expression and subcellular
      distribution of ER alpha proteins were confirmed in C2C12 cells transfected with
      ER alpha siRNA and by RT-PCR employing specific primers. The non-classical
      distribution of native pools of ER alpha in skeletal muscle cells suggests an
      alternative mode of ER localization/function.

PMID- 18348186
TI  - Protein phosphatase 1 activation and alternative splicing of Bcl-X and Mcl-1 by
      EGCG + ibuprofen.
AB  - Epigallocatechin-3-gallate (EGCG) and ibuprofen synergistically act to suppress
      proliferation and enhance apoptosis of prostate cancer cell lines, PC-3 and
      LNCaP. The purpose of this study was to investigate the mechanism of underlying
      this synergism. Most interestingly, EGCG + ibuprofen treatment in PC-3 cells
      resulted in altering the ratio of the splice variants of Bcl-X and Mcl-1,
      downregulating the mRNA levels of anti-apoptotic Bcl-X(L) and Mcl-1(L) with a
      concomitant increase in the mRNA levels of pro-apoptotic Bcl-X(s) and Mcl-1(s).
      However, there were no apparent changes in splicing variants in either ibuprofen
      or EGCG treated cells. Induction of alternative splicing was correlated with
      increased activity of protein phosphatase 1 (PP1) in EGCG + ibuprofen-treated
      cells, since pretreatment with calyculin A and tautomycin blocked EGCG +
      ibuprofen-induced alternative splicing in PC-3 cells in contrast to pretreatment
      with okadaic acid. On the other hand, EGCG + ibuprofen treatment in LNCaP cells
      did not alter splicing variants of Bcl-X and Mcl-1, despite the increase in
      protein phosphatase activity. In both cell lines, EGCG + ibuprofen inhibited cell
      proliferation synergistically. Taken together, this study demonstrate for the
      first time that EGCG + ibuprofen upregulated PP1 activity, which in turn induced
      alternative splicing of Bcl-X and Mcl-1 in a cell-type specific manner. Our study
      also demonstrates that the activation of PP1 contributes to the alternative
      splicing of Mcl-1.

PMID- 18348187
TI  - Identification of protein-coding and intronic noncoding RNAs down-regulated in
      clear cell renal carcinoma.
AB  - The clear cell subtype of renal cell carcinoma (RCC) is the most lethal and
      prevalent cancer of the urinary system. To investigate the molecular changes
      associated with malignant transformation in clear cell RCC, the gene expression
      profiles of matched samples of tumor and adjacent non-neoplastic tissue were
      obtained from six patients. A custom-built cDNA microarray platform was used,
      comprising 2292 probes that map to exons of genes and 822 probes for noncoding
      RNAs mapping to intronic regions. Intronic transcription was detected in all
      normal and neoplastic renal tissues. A subset of 55 transcripts was significantly
      down-regulated in clear cell RCC relative to the matched nontumor tissue as
      determined by a combination of two statistical tests and leave-one-out patient
      cross-validation. Among the down-regulated transcripts, 49 mapped to untranslated
      or coding exons and 6 were intronic relative to known exons of protein-coding
      genes. Lower levels of expression of SIN3B, TRIP3, SYNJ2BP and NDE1 (P < 0.02),
      and of intronic transcripts derived from SND1 and ACTN4 loci (P < 0.05), were
      confirmed in clear cell RCC by Real-time RT-PCR. A subset of 25 transcripts was
      deregulated in additional six nonclear cell RCC samples, pointing to common
      transcriptional alterations in RCC irrespective of the histological subtype or
      differentiation state of the tumor. Our results indicate a novel set of tumor
      suppressor gene candidates, including noncoding intronic RNAs, which may play a
      significant role in malignant transformations of normal renal cells.

PMID- 18348188
TI  - A new limb salvage surgery in cases of high-grade soft tissue sarcoma using
      photodynamic surgery, followed by photo- and radiodynamic therapy with acridine
      orange.
AB  - BACKGROUND: To maintain excellent limb function after tumor resection in patients
      with high-grade malignant sarcomas, we developed and established a new surgical
      adjuvant therapy using acridine orange (AO) after intra-lesional or marginal
      resection while sparing normal tissues of major nerves, vessels or bones adjacent
      to the tumor. METHOD: Our AO therapy procedure was combined with photodynamic
      surgery (PDS), photodynamic therapy (PDT) and radiodynamic therapy (RDT). In this
      study, 26 patients with primary high-grade soft tissue sarcomas were treated with
      AO therapy. RESULT: Results showed a low local recurrence rate (7.7%) and good
      local recurrence-free rate (88%) after AO therapy. Limb function of all patients
      was maintained at 100% of ISOLS criteria. CONCLUSION: Based on these results, we
      concluded that AO therapy is useful for local control after margin-positive tumor
      resection and for preserving excellent limb function in patients with high-grade
      soft tissue sarcomas.

PMID- 18348189
TI  - Alf Ketcham and his Italian friends.

PMID- 18348190
TI  - Modulation of VEGF signalling output by the Notch pathway.
AB  - The formation of blood vessels within the vascular system entails a variety of
      cellular processes, including proliferation, migration and differentiation. In
      many cases, these diverse processes need to be finely coordinated among
      neighbouring endothelial cells in order to establish a functional vascular
      network. For instance, during angiogenic sprouting specialized endothelial tip
      cells follow guidance cues and migrate extensively into avascular tissues while
      trailing stalk cells must stay connected to the patent blood vessel. The vascular
      endothelial growth factor (VEGF) and Notch signalling pathways have emerged as
      the major players in governing these different cellular behaviours. In
      particular, recent work indicates an important role for Notch signalling in
      determining how an endothelial cell responds to VEGF. In this review, we provide
      an overview of these biochemically distinct pathways and discuss how they may
      interact during endothelial cell differentiation and angiogenesis.

PMID- 18348191
TI  - The role of ATF-2 in oncogenesis.
AB  - Activating Transcription Factor-2 is a sequence-specific DNA-binding protein that
      belongs to the bZIP family of proteins and plays diverse roles in the mammalian
      cells. In response to stress stimuli, it activates a variety of gene targets
      including cyclin A, cyclin D and c-jun, which are involved in oncogenesis in
      various tissue types. ATF-2 expression has been correlated with maintenance of a
      cancer cell phenotype. However, other studies demonstrate an antiproliferative or
      apoptotic role for ATF-2. In this review, we summarize the signaling pathways
      that activate ATF-2, as well as its downstream targets. We examine the role of
      ATF-2 in carcinogenesis with respect to other bZIP proteins, using data from
      studies in human cancer cell lines, human tumours and mouse models, and we
      propose a potential model for its function in carcinogenesis, as well as a
      theoretical basis for its utility in anticancer drug design.

PMID- 18348192
TI  - Alternative models for the evolution of eyespots and of serial homology on
      lepidopteran wings.
AB  - Serial homology is widespread in organismal design, but the origin and
      individuation of these repeated structures appears to differ with the different
      types of serial homologues, and remains an intriguing and exciting topic of
      research. Here I focus on the evolution of the serially repeated eyespots that
      decorate the margin of the wings of nymphalid butterflies. In this system,
      unresolved questions relate to the evolutionary steps that lead to the appearance
      of these serial homologues and how their separate identities evolved. I present
      and discuss two alternative hypotheses. The first proposes that eyespots first
      appeared as a row of undifferentiated repeated modules, one per wing compartment,
      that later become individuated. This individuation allowed eyespots to appear and
      disappear from specific wing compartments and also allowed eyespots to acquire
      different morphologies. The second hypothesis proposes that eyespots first
      appeared as individuated single units, or groups of units, that over evolutionary
      time were co-opted into new compartments on the wing. I discuss the merits of
      each of these alternate hypotheses by finding analogies to other systems and
      propose research avenues for addressing these issues in the future.

PMID- 18348193
TI  - When did Louis Pasteur present his memoir on the discovery of molecular chirality
      to the Academie des sciences? Analysis of a discrepancy.
AB  - Louis Pasteur presented his historic memoir on the discovery of molecular
      chirality to the Academie des sciences in Paris on May 22nd, 1848. The
      literature, however, nearly completely ignores this date, widely claiming instead
      May 15th, 1848, which first surfaced in 1922 in Pasteur's collected works edited
      by his grandson Louis Pasteur Vallery-Radot. On May 21st, 1848, i.e., one day
      before Pasteur's presentation in Paris, his mother died in Arbois, eastern
      France. Informed at an unknown point in time that she was "very ill," Pasteur
      left for Arbois only after his presentation. Biographies of Pasteur by his son-in
      law Rene Vallery-Radot or the grandson, and Pasteur's collected correspondence
      edited by the grandson are incomprehensibly laconic or silent about the historic
      presentation. While no definite conclusions are possible, the evidence strongly
      suggests a deliberate alteration of the record by the biographer relatives,
      presumably for fear of adverse public judgment of Pasteur for a real or perceived
      insensitivity to a grave family medical emergency. Such fear would have been in
      accord with their hagiographic portrayal of Pasteur, and the findings raise
      questions concerning the extent of their zeal in protecting his "demigod" image.
      Universal recognition of the true date of Pasteur's announcement of molecular
      chirality is long overdue.

PMID- 18348194
TI  - Xanthohumol inhibits inflammatory factor production and angiogenesis in breast
      cancer xenografts.
AB  - Xanthohumol (XN), a natural polyphenol present in beer, is known to exert anti
      cancer effects. However, its precise mechanisms are not yet clearly defined. The
      aim of this study was to investigate the effect of oral administration of XN in
      breast cancer xenografts in nude mice. Proliferation and apoptosis were first
      examined in MCF7 cell cultures after incubation with XN by trypan blue exclusion
      assay, [3H]-thymidine incorporation, KI67 immunostaining and TUNEL. Morphological
      and histological characteristics of tumours from XN-treated or control (vehicle
      treated) mice were compared. Immunohistochemistry for proliferative, inflammatory
      and endothelial cell markers was performed and activation of nuclear factor kappa
      B (NFkappaB) pathway was assessed by ELISA. In vitro MCF7 cell proliferation
      decreased in a dose-dependent manner. Oral administration of XN to nude mice
      inoculated with MCF7 cells resulted in central necrosis within tumours, reduced
      inflammatory cell number, focal proliferation areas, increased percentage of
      apoptotic cells and decreased microvessel density. Anti-angiogenic effects of XN
      were further confirmed by immunoblotting for factor VIII expression in XN-treated
      tumours as compared to controls. Decreased immunostaining for NFkappaB,
      phosphorylated-inhibitor of kappa B and interleukin-1beta were also observed as
      well as a significant decrease in NFkappaB activity to 60% of control values.
      These novel findings indicate that XN is able to target both breast cancer and
      host cells, namely inflammatory and endothelial cells, suggesting its potential
      use as a double-edge anti-cancer agent.

PMID- 18348195
TI  - An analysis of candidate autism loci on chromosome 2q24-q33: evidence for
      association to the STK39 gene.
AB  - A susceptibility locus for autism was identified to the chromosome 2q24-q33
      region in independent cohorts of families, especially in subsets clinically
      defined with phrase speech delay (PSD). In the present work, we screened 84
      linkage-informative SNPs covering this locus in a cohort of 334 families with
      autism and in subsets identified with PSD. We observed linkage to autism with the
      highest non-parametric linkage score (NPL) of 2.79 (P = 0.002) in the PSD subset
      with at least two affected subjects. In addition, using a set of 109 additional
      gene-oriented SNPs in this interval we observed that several SNPs encompassing
      the SLC25A12 gene provided the maximum evidence for linkage (NPL = 3.32, P =
      0.0003). Using the transmission disequilibrium test to test for associations, we
      observed significant over-transmissions of rs2056202 (P = 0.006) within the
      SLC25A12 gene, rs1807984 (P = 0.007) within the STK39 gene, and rs2305586 (P =
      0.009) within the ITGA4 gene. We also found evidence for association between
      autism and two other SNPs (rs1517342, P = 0.012 and rs971257, P = 0.030) or
      haplotypes (P = 0.003) of the STK39 gene. STK39 encodes a serine/threonine kinase
      (SPAK/PASK/STE20-SPS1 homolog) abundantly expressed in the brain with roles in
      cell differentiation, cell transformation and proliferation, and in regulation of
      ion transporters. In summary, we have observed further evidence for linkage and
      association between autism and loci within the 2q24-q33 region, including at
      STK39, a novel candidate gene for autism.

PMID- 18348196
TI  - Dental enamel as a dietary indicator in mammals.
AB  - The considerable variation in shape, size, structure and properties of the enamel
      cap covering mammalian teeth is a topic of great evolutionary interest. No
      existing theories explain how such variations might be fit for the purpose of
      breaking food particles down. Borrowing from engineering materials science, we
      use principles of fracture and deformation of solids to provide a quantitative
      account of how mammalian enamel may be adapted to diet. Particular attention is
      paid to mammals that feed on 'hard objects' such as seeds and dry fruits, the
      outer casings of which appear to have evolved structures with properties similar
      to those of enamel. These foods are important in the diets of some primates, and
      have been heavily implicated as a key factor in the evolutionary history of the
      hominin clade. As a tissue with intrinsic weakness yet exceptional durability,
      enamel could be especially useful as a dietary indicator for extinct taxa.

PMID- 18348198
TI  - UHV studies of methanol decomposition on mono- and bimetallic CoPd nanoparticles
      supported on thin alumina films.
AB  - Bimetallic nanoparticles often turn out to be superior to the corresponding
      monometallic systems with respect to their catalytic properties. To study such
      effects for the methanol decomposition reaction, model catalysts were prepared by
      physical vapor deposition of Pd and Co under ultrahigh-vacuum (UHV) conditions.
      Monometallic Pd and Co particles as well as CoPd core-shell particles were
      generated on an epitaxial alumina film grown on NiAl(110). The interaction with
      methanol is examined by temperature-programmed desorption of methanol and carbon
      monoxide and by X-ray photoelectron spectroscopy. The decomposition of methanol
      proceeds in two reaction pathways independent of the particle composition:
      complete dehydrogenation towards carbon monoxide and hydrogen, and C--O bond
      scission yielding carbon deposits. Pd is the most active material studied here.
      The relative importance of the two channels varies for the different particle
      systems: on Pd dehydrogenation is preferred, whereas the C--O bond cleavage is
      more pronounced on Co. The bimetallic clusters show a moderate performance for
      both pathways. Carbon deposition poisons the model catalysts by blocking the
      adsorption sites for methoxide, which is the first intermediate product during
      methanol decomposition. In particular on Co, large amounts of carbon deposits can
      also be caused by dissociation of the final product of the dehydrogenation
      pathway, carbon monoxide. A comparison with the results of methanol decomposition
      on Co, Pd, and CoPd catalysts in continuous-flow reactors demonstrates that the
      findings of the present UHV study are relevant for catalytic performance under
      high-pressure conditions.

PMID- 18348199
TI  - Stability of anion binding with monomers of a cationic surfactant.

PMID- 18348200
TI  - Fe1-yO nanoparticles: organometallic synthesis and magnetic properties.
AB  - Non-stoichiometric wustite particles (Fe(1-y)O) are synthesized using the
      controlled room-temperature hydrolysis of the organometallic precursor
      {Fe[N(SiMe3)2]2}. Particles stabilized by hexadecylamine with a diameter of
      approximately 5 nm are obtained. For such small nanoparticles, a distorted
      crystallographic structure is evidenced by wide-angle X-ray scattering at room
      temperature and reported for the first time. The study of the magnetic properties
      indicates that these particles are composed of an antiferromagnetic core
      surrounded by a ferromagnetic shell. According to the Neel theory, we demonstrate
      that this shell consists of 1.5 % of Fe3+ ions ferromagnetically coupled with
      Fe2+ ions.

PMID- 18348201
TI  - Osteoclast inhibitory peptide-1 (OIP-1) inhibits measles virus nucleocapsid
      protein stimulated osteoclast formation/activity.
AB  - Paget's disease (PD) of bone is characterized by increased activity of large
      abnormal osteoclasts (OCLs) which contain paramyxoviral nuclear and cytoplasmic
      inclusions. MVNP gene expression has been shown to induce pagetic phenotype in
      OCLs. We previously characterized the osteoclast inhibitory peptide-1 (OIP
      1/hSca) which inhibits OCL formation/bone resorption. OIP-1 is a
      glycophosphatidylinositol (GPI)-linked membrane protein containing a 79 amino
      acid extra cellular peptide and a 32 amino acid carboxy terminal GPI-linked
      peptide (c-peptide) which is critical for OCL inhibition. In this study, we
      demonstrate that OIP-1 c-peptide significantly decreased (43%) osteoclast
      differentiation of peripheral blood mononuclear cells from patients with PD.
      Also, OIP-1 treatment to normal human bone marrow mononuclear cells transduced
      with the MVNP inhibited (41%) osteoclast precursor (CFU-GM) growth in methyl
      cellulose cultures. We further tested if OIP-1 overexpression in the OCL lineage
      in transgenic mice inhibits MVNP stimulated OCL formation. MVNP transduction and
      RANKL stimulation of OIP-1 mouse bone marrow cells showed a significant decrease
      (43%) in OCL formation and inhibition (38%) of bone resorption area compared to
      wild-type mice. Western blot analysis identified that OIP-1 decreased (3.5-fold)
      MVNP induced TRAF2 expression during OCL differentiation. MVNP or OIP-1
      expression did not affect TRAF6 levels. Furthermore, OIP-1 expression resulted in
      a significant inhibition of MVNP stimulated ASK1, Rac1, c-Fos, p-JNK, and NFATc1
      expression during OCL differentiation. These results suggest that OIP-1 inhibits
      MVNP induced pagetic OCL formation/activity through suppression of RANK
      signaling. Thus, OIP-1 may have therapeutic utility against excess bone
      resorption in patients with PD.

PMID- 18348202
TI  - Estimation of the multiple testing burden for genomewide association studies of
      nearly all common variants.
AB  - Genomewide association studies are an exciting strategy in genetics, recently
      becoming feasible and harvesting many novel genes linked to multiple phenotypes.
      Determining the significance of results in the face of testing a genomewide set
      of multiple hypotheses, most of which are producing noisy, null-distributed
      association signals, presents a challenge to the wide community of association
      researchers. Rather than each study engaging in independent evaluation of
      significance standards, we have undertaken the task of developing such standards
      for genomewide significance, based on data collected by the International
      Haplotype Map Consortium. We report an estimated testing burden of a million
      independent tests genomewide in Europeans, and twice that number in Africans. We
      further identify the sensitivity of the testing burden to the required
      significance level, with implications to staged design of association studies.

PMID- 18348203
TI  - Simple association analysis combining data from trios/sibships and unrelated
      controls.
AB  - We consider genetic association analysis that combines data from case-parent
      trios/sibships and unrelated controls. A general and simple methodology is
      proposed, using a weighted least-squares approach to combine separate information
      from the case-parent/case-sibling analysis and the case-unrelated control
      analysis. The new proposal improves over the existing methods in that it requires
      no assumptions and estimation on the mating-type distribution. Simulation results
      show that the new method competes well with the likelihood-based method when the
      latter is applicable, and achieves substantial power gains over separate analyses
      in general. Therefore, the proposed combined association analysis can enjoy wide
      applications, including the multiallele/locus, haplotype, and genome-wide
      association studies.

PMID- 18348204
TI  - Curcumin downregulates H19 gene transcription in tumor cells.
AB  - Curcumin (diferuloymethane), a natural compound used in traditional medicine,
      exerts an antiproliferative effect on various tumor cell lines by an incompletely
      understood mechanism. It has been shown that low doses of curcumin downregulate
      DNA topoisomerase II alpha (TOP2A) which is upregulated in many malignances. The
      activity of TOP2A is required for RNA polymerase II transcription on chromatin
      templates. Recently, it has been reported that CTCF, a multifunctional
      transcription factor, recruits the largest subunit of RNA polymerase II (LS Pol
      II) to its target sites genome-wide. This recruitment of LS Pol II is more
      pronounced in proliferating cells than in fully differentiated cells. As
      expression of imprinted genes is often altered in tumors, we investigated the
      potential effect of curcumin treatment on transcription of the imprinted H19
      gene, located distally from the CTCF binding site, in human tumor cell lines HCT
      116, SW 620, HeLa, Cal 27, Hep-2 and Detroit 562. Transcription of TOP2A and
      concomitantly H19 was supressed in all tumor cell lines tested. Monoallelic IGF2
      expression was maintained in curcumin-treated cancer cells, indicating the
      involvement of mechanism/s other than disturbance of CTCF insulator function at
      the IGF2/H19 locus. Curcumin did not alter H19 gene transcription in primary cell
      cultures derived from normal human tissues.

PMID- 18348205
TI  - A functional polymorphism, rs6280, in DRD3 is significantly associated with
      nicotine dependence in European-American smokers.
AB  - Nicotine enhances reward functions in the mesocorticolimbic dopamine system in
      general and the nucleus accumbens in particular. The genes encoding dopamine
      receptors are thus plausible candidates for involvement in nicotine dependence
      (ND). We investigated 13 single nucleotide polymorphisms (SNPs) spanning a region
      of the dopamine D(3) receptor gene (DRD3) to determine whether DRD3 is associated
      with ND. We studied a set of 2,037 subjects in 602 nuclear families representing
      two distinct American populations using three ND measures, namely, smoking
      quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for
      ND (FTND). In the family based association study, we found that SNP rs6280 showed
      a strong association with ND in European-Americans (EAs) and the pooled sample,
      whereas SNPs rs1486012 and rs963468 had weak associations with ND in African
      Americans (AAs) and the pooled sample. Further haplotype analysis with all
      contiguous 3-SNP groups revealed relatively weak evidence for association of DRD3
      with ND in the EA and pooled samples. The results indicate that DRD3 is
      significantly associated with ND in EAs, and that rs6280, a functional
      polymorphism causing an amino acid change of serine to glycine (Ser9Gly) in the N
      terminal extracellular domain of the D(3) receptor, likely is causative of the
      association between DRD3 and ND.

PMID- 18348206
TI  - Comments on "Novelty seeking and the dopamine D4 receptor gene (DRD4) revisited
      in Asians: Haplotype characterization and relevance of the 2-repeat allele" by C.
      Reist et al. Am J Med Genet B Neuropsychiatr Genet 2007;144(4):453-457.

PMID- 18348207
TI  - Comments on "Effects of a 2450 MHz high-frequency electromagnetic field with a
      wide range of SARs on the induction of heat-shock proteins in A172 cells" by Wang
      et al. (Bioelectromagnetics 27: 479-486, 2006).

PMID- 18348208
TI  - Challenges in implementing CD4 testing in resource-limited settings.
AB  - The scale-up of HIV antiretroviral therapy in recent years has led to a rapid
      increase in CD4 and CD4% count capacity to meet the diagnostic needs of staging
      and monitoring disease progression and treatment efficacy in adults and infants.
      The speed of implementation of this technology has been unrivalled in recent
      years and has met challenges with technology selection, laboratory infrastructure
      development, human resource limitations, cost-effectiveness, instrument
      maintenance, and ensuring testing access and quality. The lessons learned from
      dealing with these challenges have helped strengthen existing laboratory systems
      for other diagnostics. They may also facilitate the implementation of new
      diagnostics in future.

PMID- 18348209
TI  - Bracovirus gene products are highly divergent from insect proteins.
AB  - Recently, several polydnavirus (PDV) genomes have been completely sequenced. The
      dsDNA circles enclosed in virus particles and injected by wasps into caterpillars
      appear to mainly encode virulence factors potentially involved in altering host
      immunity and/or development, thereby allowing the survival of the parasitoid
      larvae within the host tissues. Parasitoid wasps generally inject virulence
      factors produced in the venom gland. As PDV genomes are inherited vertically by
      wasps through a proviral form, wasp virulence genes may have been transferred to
      this chromosomal form, leading to their incorporation into virus particles.
      Indeed, many gene products from Cotesia congregata bracovirus (CcBV), such as
      PTPs, IkappaB-like, and cystatins, contain protein domains conserved in
      metazoans. Surprisingly however, CcBV virulence gene products are not more
      closely related to insect proteins than to human proteins. To determine whether
      the distance between CcBV and insect proteins is a specific feature of BV
      proteins or simply reflects a general high divergence of parasitoid wasp
      products, which might be due to parasitic lifestyle, we have analyzed the
      sequences of wasp genes obtained from a cDNA library. Wasp sequences having a
      high similarity with Apis mellifera genes involved in a variety of biological
      functions could be identified indicating that the high level of divergence
      observed for BV products is a hallmark of these viral proteins. We discuss how
      this divergence might be explained in the context of the current hypotheses on
      the origin and evolution of wasp-bracovirus associations.

PMID- 18348210
TI  - Comparison of three methods of parasitoid polydnavirus genomic DNA isolation to
      facilitate polydnavirus genomic sequencing.
AB  - A major long-term goal of polydnavirus (PDV) genome research is to identify novel
      virally encoded molecules that may serve as biopesticides to target insect pests
      that threaten agriculture and human health. As PDV viral replication in cell
      culture in vitro has not yet been achieved, several thousands of wasps must be
      dissected to yield enough viral DNA from the adult ovaries to carry out PDV
      genomic sequencing. This study compares three methods of PDV genomic DNA
      isolation for the PDV of Cotesia flavipes, which parasitizes the sugarcane borer,
      Diatraea saccharalis, preparatory to sequencing the C. flavipes bracovirus
      genome. Two of these protocols incorporate phenol-chloroform DNA extraction steps
      in the procedure and the third protocol uses a modified Qiagen DNA kit method to
      extract viral DNA. The latter method proved significantly less time-consuming and
      more cost-effective. Efforts are currently underway to bioengineer insect
      pathogenic viruses with PDV genes, so that their gene products will enhance
      baculovirus virulence for agricultural insect pests, either via suppression of
      the immune system of the host or by PDV-mediated induction of its developmental
      arrest. Sequencing a growing number of complete PDV genomes will enhance those
      efforts, which will be facilitated by the study reported here.

PMID- 18348211
TI  - Two homologous parasitism-specific proteins encoded in Cotesia plutellae
      bracovirus and their expression profiles in parasitized Plutella xylostella.
AB  - A wasp, Cotesia plutellae, parasitizes the diamondback moth, Plutella xylostella,
      and interrupts host physiology for wasp survival and development. Identification
      of parasitism-specific factors would be helpful to understand the host-parasitoid
      interaction. This study focused on identification of a 15-kDa protein found only
      in plasma of the parasitized P. xylostella. Degenerate primers were designed
      after N-terminal amino acid sequencing of the parasitism-specific protein and
      used to clone the corresponding gene from the parasitized P. xylostella by a
      nested reverse transcriptase-polymerase chain reaction (RT-PCR). Two homologous
      genes were cloned and identified as "CpBV15alpha" and "CpBV15beta," respectively,
      due to the identical size (158 amino acid residues) of the predicted open reading
      frames, in which they shared amino acid sequences in both terminal regions, but
      varied in internal sequences. Southern hybridization analysis indicated that both
      genes were located on C. plutellae bracovirus genome. Real-time quantitative RT
      PCR revealed that both genes were mostly expressed at the late parasitization
      period, which was further confirmed by an immunoblotting assay using CpBV15
      antibody. A recombinant CpBV15 protein was produced from Sf9 cells via a
      baculovirus expression system. The purified CpBV15 protein could enter hemocytes
      of P. xylostella and were localized in the cytosol. Along with the sequence
      similarities of CpBV15s with eukaryotic initiation factors, their putative
      biological role has been discussed in terms of the host translation inhibitory
      factor.

PMID- 18348212
TI  - A new method for assigning common spot boundaries for multiple gels in two
      dimensional gel electrophoresis.
AB  - The benefits of defining common spot boundaries when several gels from 2-DE are
      compared and analyzed have lately been stressed by both commercial software
      producers and users of this software. Though the importance of common spot
      boundaries is clearly stated, few reports exist that target this issue
      explicitly. In this study a method for defining common spots boundaries is
      developed, called the spot density method. The method consists of the following
      steps: segmentation and spot identification on each individual gel, transferring
      the spot-center coordinates for all gels onto a single new gel, collecting spot
      centers clustered together in the new gel and finally assigning pixels and new
      spot boundaries based on the spots in each cluster. The method is compared to a
      synthetic gel approach, and validated by visual inspection of three
      representative areas in the gels. The gel images need to be aligned prior to
      segmentation and spot identification, but the method can be used regardless of
      the choice of segmentation procedure. This makes the method an easy extension to
      existing methods for spot identification and matching. Conclusions based on the
      visual inspection are that the spot density method identifies partly overlapping
      spots and low-intensity spots better than the synthetic gel approach.

PMID- 18348213
TI  - A multivariate spot filtering model for two-dimensional gel electrophoresis.
AB  - Image segmentation plays an important role in the automatic analysis of protein
      spots in 2-DE. Using image segments representing protein spots, the amount of
      protein in each segment can be quantified, and corresponding segments can be
      matched and compared for multiple gels. However, the common presence of image
      segments caused by noise and unwanted artefacts highly disturb the analysis and
      comparison of the gels. Common sources of such artefacts are cracks in the gel
      surface, fingerprints, dust and other pollutions. It would be advantageous to
      remove these unwanted artefacts during or after the segmentation procedure. To
      achieve this task a multivariate spot filtering model is developed using image
      segments from a gel segmentation. Parameters in the model are based on texture,
      shape and intensity measurements of the image segments. The model successfully
      managed to separate segments caused by noise, artefacts and cracks from image
      segments representing true protein spots. The classification method used is
      discriminant partial least squares regression.

PMID- 18348214
TI  - An improved pixel-based approach for analyzing images in two-dimensional gel
      electrophoresis.
AB  - An improved pixel-based approach for analyzing 2-DE images is presented. The key
      feature of the method is to create a mask based on all gels in the experiment
      using image morphology, followed by multivariate analysis on the pixel level. The
      method reduces the impact of noise and background by identifying regions in the
      image where protein spots are present, but make no assumption on individual spot
      boundaries for isolated spots. This makes it possible to detect significant
      changes in complex regions, and visualize these changes over multiple gels in an
      easy way. False missing values and spot volumes caused by imposing erroneous spot
      boundaries are thus circumvented. The approach presented gives improved pixel
      based information from the gels, and is also an alternative to existing methods
      for data-reduction, significance testing and visualization of 2-DE data. Results
      are compared with software using a common spot boundary approach on an experiment
      consisting of 35 full size gel images. Gel alignment is required before analysis.

PMID- 18348218
TI  - Nanoscale actuation of electrokinetic flows on thermoreversible surfaces.
AB  - We report on a novel approach for controlling nanohydrodynamic properties at the
      solid-liquid interfaces through the use of stimuli-responding polymer coatings.
      The end-tethered polymers undergo a phase separation upon external activation.
      The reversible change in the thickness and polarity of the grafted polymers
      yields in a dynamic control of the surface-generated, electrokinetic phenomena.
      Nonactivated, swollen polymers are thicker than the electrical double layer (EDL)
      and prohibit the development of an EOF even on charged surfaces. On the other
      hand, activated polymer chains shrink and become thinner than the EDL and allow
      for the EOF to build up unimpeded. We show here that, for given experimental
      conditions, the EOF velocity on the shrunken surface is 35 times greater than the
      one on the nonactivated surface. Furthermore, we reveal that coupling of such
      surfaces with dense arrays of thermal actuators developed in our laboratory can
      lead to novel micro- and nanofluidic devices.

PMID- 18348219
TI  - Detection of carbonyl-modified proteins in interfibrillar rat mitochondria using
      N'-aminooxymethylcarbonylhydrazino-D-biotin as an aldehyde/keto-reactive probe in
      combination with Western blot analysis and tandem mass spectrometry.
AB  - There is now a large body of supporting data available that links oxidative
      modifications of proteins to a large number of diseases, degenerative disorders
      and aging. However, the detailed analysis of oxidative protein modifications
      remains challenging. Here, we report a new efficient method for identification of
      oxidatively modified proteins in complex biological samples which is based on the
      use of an aldehyde-reactive probe, N'-aminooxymethylcarbonylhydrazino-D-biotin
      (ARP), in combination with Western-type analyses and MS. The biotinylated
      hydroxylamine derivative forms a chemically stable oxime derivative with the
      aldehyde/keto group found in carbonyl-modified proteins. The biotin tag is
      detected by avidin affinity staining. ARP-positive proteins are subsequently
      subjected to in-gel trypsinization and MS/MS for protein identification. We
      demonstrate the usefulness of the method for the analysis of protein extracts
      obtained from interfibrillar heart mitochondria (IFM) from young and old rats. In
      this study, we identified as putative major protein targets of oxidative
      modifications the mitochondrial matrix protein, aconitase, the inner
      mitochondrial membrane protein, ADP/ATP translocase, and constituents of the
      electron transport chain complexes IV and V. An age-related increase of carbonyl
      levels was found for aconitase and ATP synthase.

PMID- 18348220
TI  - Determination of organic anions in atmospheric aerosol samples by capillary
      electrophoresis after reversed pre-electrophoresis.
AB  - This work presents the determination of low-molecular-mass (LMM) organic acids by
      CE after extraction with MeOH and preconcentration by evaporation. The
      interference arising from the simultaneous concentration of fast mobile anions
      (chloride, nitrate, and sulfate) at levels 200 times higher than those of LMM
      organic acids was reduced by the application of reversed pre-electrophoresis
      (RPE) as clean-up technique. This methodology allows for an effective elimination
      of high levels of fast mobile anions from the capillary before the separation has
      taken place, although analytes are also partially eliminated according to their
      electrophoretic velocities. In order to achieve an accurate quantification of
      organic anions, the use of a mathematical correction based on the linear relation
      between the analyte's effective volume removed during RPE and its mobility is
      proposed. Methods based on the use of one and two internal standards are
      discussed and evaluated. The proposed method is applied to the determination of
      organic acids in atmospheric particulate matter samples.

PMID- 18348221
TI  - On-line measurements of delta(15)N in biological fluids by a modified continuous
      flow elemental analyzer with an isotope-ratio mass spectrometer.
AB  - A modified continuous-flow elemental analyzer coupled to an isotope-ratio mass
      spectrometer (modified EA-IRMS) was tested for on-line delta(15)N measurement on
      urea solution and biological fluids (e.g. urine). The elemental analyzer
      configuration was adapted by adding a U-shaped cold trap and an X-pattern four
      way valve for on-line trapping/venting of water from the liquid samples. Results
      indicate that the delta(15)N ratios show little variation (standard deviation
      (SD) = 0.05 per thousand) with a sample size above the equivalent N yield of 0.2
      mg urea (0.092 mg N) when the mass spectrometer conditions were carefully
      optimized. By contrast, a significant logarithmic decrease in delta(15)N with
      sample size was observed but this can be offset by applying a linearity
      correction or blank correction when the sample size is between equivalent N
      yields of 0.05 and 0.2 mg urea. The blank corrected delta(15)N ratios give an
      overall precision of approximately 0.16 per thousand whereas the average
      precision for delta(15)N corrected using combined linearity and shift correction
      is 0.05 per thousand. The relatively large variation in blank corrected
      delta(15)N values may be attributed to the variability of the blank delta(15)N in
      the sequence. Therefore, the blank correction should be carefully performed in
      routine measurements. As a result, the linearity range of a modified EA-IRMS can
      be extended to a minimum sample size of 0.023 mg N. In addition, the
      reproducibility of the new system is good, as indicated by the precision (<0.2
      per thousand) for a set of standards and unknowns. The data show that fluids
      containing nitrogen can be successfully analyzed in the modified EA-IRMS.

PMID- 18348222
TI  - Performance optimisation of a new-generation orthogonal-acceleration quadrupole
      time-of-flight mass spectrometer.
AB  - Orthogonal-acceleration quadrupole time-of-flight (oa-QTOF) mass spectrometers,
      employed for accurate mass measurement, have been commercially available for well
      over a decade. A limitation of the early instruments of this type was the narrow
      ion abundance range over which accurate mass measurements could be made with a
      high degree of certainty. Recently, a new generation of oa-QTOF mass
      spectrometers has been developed and these allow accurate mass measurements to be
      recorded over a much greater range of ion abundances. This development has
      resulted from new ion detection technology and improved electronic stability or
      by accurate control of the number of ions reaching the detector. In this report
      we describe the results from experiments performed to evaluate the mass
      measurement performance of the Bruker micrOTOF-Q, a member of the new-generation
      oa-QTOFs. The relationship between mass accuracy and ion abundance has been
      extensively evaluated and mass measurement accuracy remained stable (+/-1.5 m m/z
      units) over approximately 3-4 orders of magnitude of ion abundance. The second
      feature of the Bruker micrOTOF-Q that was evaluated was the SigmaFit function of
      the software. This isotope pattern-matching algorithm provides an exact numerical
      comparison of the theoretical and measured isotope patterns as an additional
      identification tool to accurate mass measurement. The smaller the value, the
      closer the match between theoretical and measured isotope patterns. This
      information is then employed to reduce the number of potential elemental formulae
      produced from the mass measurements. A relationship between the SigmaFit value
      and ion abundance has been established. The results from the study for both mass
      accuracy and SigmaFit were employed to define the performance criteria for the
      micrOTOF-Q. This provided increased confidence in the selection of elemental
      formulae resulting from accurate mass measurements.

PMID- 18348223
TI  - Carbon isotope determination for separate components of heterogeneous materials
      using coupled thermogravimetric analysis/isotope ratio mass spectrometry.
AB  - A gas-tight thermal analysis system (Netzsch STA 449C Jupiter) has been connected
      to an isotope ratio mass spectrometer (PDZ Europa 20-20) via an interface
      containing an oxidizing furnace, water trap, and gas-sampling valve. Using this
      system, delta(13)C has been measured for CO(2) derived from the thermal
      decomposition of carbonate and oxalate minerals and organic materials at
      temperatures that correspond to different decomposition events. There is close
      agreement between measured and published delta(13)C values for carbonate and
      oxalate minerals, which have simple decarbonation reactions on heating. Cellulose
      and lignin-rich materials show much more complex thermal decomposition,
      reflecting differences in their purity and structure, and measured delta(13)C
      values vary with the temperature of gas sampling. Provided that measurements are
      made at temperatures that correspond to the decomposition of cellulose and lignin
      (indicated by maximum weight loss), internally consistent data can be obtained.
      However, measurements for cellulose and lignin are systematically enriched in
      delta(13)C (by up to 1.4 per thousand) with respect to those reported for
      reference materials, possibly due to the slower combustion kinetics (compared
      with EA-IRMS). Thermogravimetric analysis/isotope ratio mass spectrometry (TG
      IRMS) is ideal for materials and samples for which it is not possible to use
      other isotopic measurement techniques, for example because of sample
      heterogeneity.

PMID- 18348224
TI  - Spiking of serum specimens with exogenous reporter peptides for mass spectrometry
      based protease profiling as diagnostic tool.
AB  - Serum is a difficult matrix for the identification of biomarkers by mass
      spectrometry (MS). This is due to high-abundance proteins and their complex
      processing by a multitude of endogenous proteases making rigorous standardisation
      difficult. Here, we have investigated the use of defined exogenous reporter
      peptides as substrates for disease-specific proteases with respect to improved
      standardisation and disease classification accuracy. A recombinant N-terminal
      fragment of the Adenomatous Polyposis Coli (APC) protein was digested with
      trypsin to yield a peptide mixture for subsequent Reporter Peptide Spiking (RPS)
      of serum. Different preanalytical handling of serum samples was simulated by
      storage of serum samples for up to 6 h at ambient temperature, followed by RPS,
      further incubation under standardised conditions and testing for stability of
      protease-generated MS profiles. To demonstrate the superior classification
      accuracy achieved by RPS, a pilot profiling experiment was performed using serum
      specimens from pancreatic cancer patients (n = 50) and healthy controls (n = 50).
      After RPS six different peak categories could be defined, two of which
      (categories C and D) are modulated by endogenous proteases. These latter are
      relevant for improved classification accuracy as shown by enhanced disease
      specific classification from 78% to 87% in unspiked and spiked samples,
      respectively. Peaks of these categories presented with unchanged signal
      intensities regardless of preanalytical conditions. The use of RPS generally
      improved the signal intensities of protease-generated peptide peaks. RPS
      circumvents preanalytical variabilities and improves classification accuracies.
      Our approach will be helpful to introduce MS-based proteomic profiling into
      routine laboratory testing.

PMID- 18348225
TI  - Zinc porphyrin-driven assembly of gold nanofingers.
AB  - Nanofingers of gold covered by porphyrins are prepared by a combination of atomic
      manipulation and surface self-organization. A submonolayer of zinc(II) 5,10,15,20
      tetrakis(4-tert-butylphenyl)-porphyrin (ZnTBPP) axially ligated to a self
      assembled monolayer of 4-aminothiophenol (4-ATP) on Au(111) is prepared and
      studied using a combination of ultrahigh vacuum techniques. Under the electric
      field produced by the STM tip, the relatively weakly bound Au surface atoms along
      the discommensuration lines become mobile due to the strong bond to 4-ATP, while
      the tendency of the porphyrins towards self-assembly result in a collective
      motion of gold clusters. The clusters diffuse onto the surface following well
      defined pathways along the [112] direction and then reach the step edges where
      they assembled, thus forming nanofingers. First-principles density functional
      theory calculations demonstrate the reduction of the binding energies between the
      surface gold clusters and the substrate induced by adsorption of thiols. Scanning
      tunneling microscopy images show assemblies across three adjacent
      discommensuration lines of the Au(111)-(22 x square root 3) reconstruction, which
      collectively diffuse along these lines to form islands nucleated at step edges.

PMID- 18348226
TI  - Electrical characterization of the mutual influences between gas molecules and
      single-walled carbon nanotubes.

PMID- 18348227
TI  - Controlling Co-tunneling currents in nanoparticle networks using spin-polarized
      wire molecules.

PMID- 18348228
TI  - The nature of graphite- and pyridinelike nitrogen configurations in carbon
      nitride nanotubes: dependence on diameter and helicity.

PMID- 18348229
TI  - A genetic analysis of carbon-nanotube-binding proteins.

PMID- 18348230
TI  - Functional Fe3O4/TiO2 core/shell magnetic nanoparticles as photokilling agents
      for pathogenic bacteria.
AB  - A photokilling approach for pathogenic bacteria is demonstrated using a new type
      of magnetic nanoprobe as the photokilling agent. In addition to their magnetic
      property, the nanoprobes have other features including a photocatalytic property
      and the capacity to target bacteria. The nanoprobes comprise iron oxide/titania
      (Fe(3)O(4)@TiO(2)) core/shell magnetic nanoparticles. As dopamine molecules can
      self-assemble onto the surface of the titania substrate, dopamine is used as the
      linker to immobilize succinic anhydride onto the surfaces of the Fe(3)O(4)@TiO(2)
      nanoparticles. This is followed by the immobilization of IgG via amide bonding.
      We demonstrate that the IgG-Fe(3)O(4)@TiO(2) magnetic nanoparticles not only have
      the capacity to target several pathogenic bacteria, but they also can effectively
      inhibit the cell growth of the bacteria targeted by the nanoparticles under
      irradiation of a low-power UV lamp within a short period. Staphylococcus
      saprophyticus, Streptococcus pyogenes, and antibiotic-resistant bacterial
      strains, such as multiantibiotic-resistant S. pyogenes and methicillin-resistant
      Staphylococcus aureus (MRSA), are used to demonstrate the feasibility of this
      approach.

PMID- 18348237
TI  - No advances without methods in biotech.

PMID- 18348242
TI  - "Antibodies--Europe. Engineering the next generation of antibodies".

PMID- 18348243
TI  - The forensic use of DNA: Scientific success story, ethical minefield.

PMID- 18348244
TI  - Managing science: is the Cudos still in place?

PMID- 18348245
TI  - Pregabalin in the discontinuation of long-term benzodiazepines' use.
AB  - OBJECTIVE: Tolerance, dependence, and adverse effects on cognitive functions are
      well-known consequences of long-term use of benzodiazepines (BDZ), especially at
      high doses, raising thorny therapeutic problems in their discontinuation. One
      promising pharmacological agent in BDZ discontinuation might be the newer anti
      epileptic pregabalin, already successfully tested in the treatment of anxiety
      disorders. METHODS: We report on a sample of 15 patients with long-term, mostly
      high-dose dependence from BDZ, treated with pregabalin in an open-label study at
      doses 225-900 mg. RESULTS: All patients discontinued successfully BDZ in 3-14
      weeks, moreover with a significant reduction of their previous anxiety levels
      under BDZ. In addition, patients showed also a significant amelioration in their
      cognitive functioning. Pregabalin's side-effects were mild and transient, lasting
      only during the first 2 weeks of treatment. CONCLUSION: Although preliminary, our
      findings suggest that pregabalin may be one new promising agent in the treatment
      of BDZ dependence.

PMID- 18348247
TI  - Papers selected from the symposium "Parasitoid Polydnaviruses: Genomes and
      Physiological Functions," presented at the 11th International Congress on
      Parasitology in August 2006. Preface.

PMID- 18348246
TI  - Prophenoloxidases 1 and 2 from the spruce budworm, Choristoneura fumiferana:
      molecular cloning and assessment of transcriptional regulation by a polydnavirus.
AB  - Immune challenge in arthropods is frequently accompanied by melanization of the
      hemolymph, a reaction triggered by the activation of prophenoloxidase (PPO).
      Because their immature stages are spent inside the hemocoel of insect larvae,
      endoparasitoids have evolved strategies to escape or counter melanin formation.
      Very little molecular information is available on these endoparasitoid
      counterstrategies. We have sought to shed light on the inhibition of melanization
      in the spruce budworm, Choristoneura fumiferana, by the parasitic wasp Tranosema
      rostrale, by cloning two host PPO homologs and studying their transcriptional
      regulation after parasitization. The two polypeptides are encoded by transcripts
      of approximately 3.3 kb (for CfPPO1) and 3.0 kb (for CfPPO2) and possess
      structural features typical of other insect PPOs. While there appears to be a
      single CfPPO2 gene in the C. fumiferana genome, we detected three CfPPO1 mRNA
      variants displaying insertions/deletions in the 3' untranslated region,
      suggesting that there may be more than one CfPPO1 gene copy. Both CfPPO1 and
      CfPPO2 were expressed at high levels in C. fumiferana 6th instars, and
      parasitization by T. rostrale had no apparent impact on the level of their
      transcripts. Injection of a large dose (0.5 female-equivalent) of polydnavirus
      laden calyx fluid extracted from T. rostrale, which is known to inhibit
      melanization in C. fumiferana, only caused a transient decrease in CfPPO1 and
      CfPPO2 transcript accumulation at 2-3 d post injection. It thus appears that
      transcriptional downregulation of C. fumiferana PPO by T. rostrale plays a minor
      role in the inhibition of hemolymph melanization in this host-parasitoid system.

PMID- 18348248
TI  - On the development of neural diversity in the brain.
AB  - The FEBS meeting titled "Generating neural diversity in the brain" took place on
      the island of Capri, from October 13-16. This high-level workshop was the 20(th)
      in a symposium series organized by the IGB (Instituto Genetica et Biophysica) of
      Naples funded by international agencies including FEBS, EMBO, European
      commission. The series is unusual in featuring first-rank international scientist
      speakers for a meeting whose audience consists primarily of students and post
      docs. The endeavour is thus more explicitly educational than many major meetings
      and the young audience helps create a lively atmosphere. With intense morning and
      evening sessions, the afternoons are left free for the participants to explore
      the island, go swimming or relax.

PMID- 18348249
TI  - Persea americana (avocado): bringing ancient flowers to fruit in the genomics
      era.
AB  - The avocado (Persea americana) is a major crop commodity worldwide. Moreover,
      avocado, a paleopolyploid, is an evolutionary "outpost" among flowering plants,
      representing a basal lineage (the magnoliid clade) near the origin of the
      flowering plants themselves. Following centuries of selective breeding, avocado
      germplasm has been characterized at the level of microsatellite and RFLP markers.
      Nonetheless, little is known beyond these general diversity estimates, and much
      work remains to be done to develop avocado as a major subtropical-zone crop.
      Among the goals of avocado improvement are to develop varieties with fruit that
      will "store" better on the tree, show uniform ripening and have better post
      harvest storage. Avocado transcriptome sequencing, genome mapping and partial
      genomic sequencing will represent a major step toward the goal of sequencing the
      entire avocado genome, which is expected to aid in improving avocado varieties
      and production, as well as understanding the evolution of flowers from non
      flowering seed plants (gymnosperms). Additionally, continued evolutionary and
      other comparative studies of flower and fruit development in different avocado
      strains can be accomplished at the gene expression level, including in comparison
      with avocado relatives, and these should provide important insights into the
      genetic regulation of fruit development in basal angiosperms.

PMID- 18348250
TI  - It's not random anymore.

PMID- 18348251
TI  - Regulation of mammalian gene expression by retroelements and non-coding tandem
      repeats.
AB  - Genomes of higher eukaryotes contain abundant non-coding repeated sequences whose
      overall biological impact is unclear. They comprise two categories. The first
      consists of retrotransposon-derived elements. These are three major families of
      retroelements (LINEs, SINEs and LTRs). SINEs are clustered in gene-rich regions
      and are found in promoters of genes while LINEs are concentrated in gene-poor
      regions and are depleted from promoters. The second class consists of non-coding
      tandem repeats (satellite DNAs and TTAGGG arrays), which are associated with
      mammalian centromeres, heterochromatin and telomeres. Terminal TTAGGG arrays are
      involved in telomere capping and satellite DNAs are located in heterochromatin,
      which is implicated in transcription silencing by gene repositioning
      (relocalization). It is unknown whether interstitial TTAGGG sequences, which are
      present in many vertebrates, have a function. Here, evidence will be presented
      that retroelements and TTAGGG arrays are involved in regulation of gene
      expression. Retroelements can provide binding sites for transcription factors and
      protect promoter CpG islands from repressive chromatin modifications, and may be
      also involved in nuclear compartmentalization of transcriptionally active and
      inactive domains. Interstitial telomere-like sequences can form dynamically
      maintained three-dimensional nuclear networks of transcriptionally inactive
      domains, which may be involved in transcription silencing like classic
      heterochromatin.

PMID- 18348252
TI  - Studying immunity at the whole organism level.

PMID- 18348254
TI  - Non-invasive analysis of cell cycle dynamics in single living cells with Raman
      micro-spectroscopy.
AB  - Raman micro-spectroscopy is a laser-based technique which enables rapid and non
      invasive biochemical analysis of cells and tissues without the need for labels,
      markers or stains. Previous characterization of the mammalian cell cycle using
      Raman micro-spectroscopy involved the analysis of suspensions of viable cells and
      individual fixed and/or dried cells. Cell suspensions do not provide cell
      specific information, and fixing/drying can introduce artefacts which distort
      Raman spectra, potentially obscuring both qualitative and quantitative analytical
      results. In this article, we present Raman spectral characterization of
      biochemical changes related to cell cycle dynamics within single living cells in
      vitro. Raman spectra of human osteosarcoma cells synchronized in G(0)/G(1), S,
      and G(2)/M phases of the cell cycle were obtained and multivariate statistics
      applied to analyze the changes in cell spectra as a function of cell cycle phase.
      Principal components analysis identified spectral differences between cells in
      different phases, indicating a decrease in relative cellular lipid contribution
      to Raman spectral signatures from G(0)/G(1) to G(2)/M, with a concurrent relative
      increase in signal from nucleic acids and proteins. Supervised linear
      discriminant analysis of spectra was used to classify cells according to cell
      cycle phase, and exhibited 97% discrimination between G(0)/G(1)-phase cells and
      G(2)/M-phase cells. The non-invasive analysis of live cell cycle dynamics with
      Raman micro-spectroscopy demonstrates the potential of this approach to
      monitoring biochemical cellular reactions and processes in live cells in the
      absence of fixatives or labels.

PMID- 18348255
TI  - The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced
      apoptosis of hippocampal neural cells.
AB  - This study investigated the frequency of apoptosis in rat hippocampal neural
      cells after intraperitoneal nicotine injection, examining the roles of the
      inflammatory markers myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF
      alpha) in nicotine-induced brain damage and the protective effects of three known
      antioxidant agents, N-acetylcysteine (NAC), erdosteine, and vitamin E. Female
      Wistar rats were divided into seven groups, each composed of nine rats: 2
      negative control groups, 2 positive control groups, one erdosteine-treated group
      (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group
      (500 mg/kg). Nicotine was intraperitoneally injected at a dosage of 0.6 mg/kg for
      21 days. Following nicotine injection, the antioxidants were administered orally;
      treatment was continued until the rats were killed. Apoptosis level in
      hippocampal neural cells was determined by using TUNEL (terminal deoxynucleotidyl
      transferase-mediated dUTP nick endlabeling) method. Staining of cytoplasmic TNF
      alpha in hippocampal neural cells and hippocampus MPO activity were evaluated by
      immunohistochemistry. Nicotine administration had no effect on local TNF-alpha
      production, or hippocampal MPO activity. The treatments with erdosteine, NAC and
      vitamin E significantly reduced the rate of nicotine-induced hippocampal neural
      cell apoptosis. This findings suggest that erdosteine and NAC can be as effective
      as vitamin E in protecting against nicotine-induced hippocampal neural cell
      apoptosis.

PMID- 18348256
TI  - Differential regulation of HSP70 expression by the JNK kinases SEK1 and MKK7 in
      mouse embryonic stem cells treated with cadmium.
AB  - JNK, a member of the mitogen-activated protein kinases (MAPKs), is activated by
      the MAPK kinases SEK1 and MKK7 in response to environmental stresses. In the
      present study, the effects of CdCl2 treatment on MAPK phosphorylation and HSP70
      expression were examined in mouse embryonic stem (ES) cells lacking the sek1
      gene, the mkk7 gene, or both. Following CdCl2 exposure, the phosphorylation of
      JNK, p38, and ERK was suppressed in sek1-/- mkk7-/- cells. When sek1-/- or mkk7-/
      cells were treated with CdCl2, JNK phosphorylation, but not the phosphorylation
      of either p38 or ERK, was markedly reduced, while a weak reduction in p38
      phosphorylation was observed in sek1-/- cells. Thus, both SEK1 and MKK7 are
      required for JNK phosphorylation, whereas their role in p38 and ERK
      phosphorylation could overlap with that of another kinase. We also observed that
      CdCl2-induced HSP70 expression was abolished in sek1-/- mkk7-/- cells, was
      reduced in sek1-/- cells, and was enhanced in mkk7-/- cells. Similarly, the
      phosphorylation of heat shock factor 1 (HSF1) was decreased in sek1-/- mkk7-/-
      and sek1-/- cells, but was increased in mkk7-/- cells. Transfection with siRNA
      specific for JNK1, JNK2, p38, ERK1, or ERK2 suppressed CdCl2-induced HSP70
      expression. In contrast, silencing of p38 or p38 resulted in further accumulation
      of HSP70 protein. These results suggest that HSP70 expression is up-regulated by
      SEK1 and down-regulated by MKK7 through distinct MAPK isoforms in mouse ES cells
      treated with CdCl2.

PMID- 18348257
TI  - Revisiting metatropic dysplasia: presentation of a series of 19 novel patients
      and review of the literature.
AB  - Metatropic dysplasia (MD-OMIM: 156530 and 250600) is a rare chondrodysplasia
      characterized by short limbs with limitation and enlargement of joints and
      usually severe kyphoscoliosis, first described in 1893. Up until now, 81 other
      patients have been reported. The phenotypic variability of MD has led to a
      classification based on radiological anomalies dividing into three different
      types: a lethal autosomal recessive form, an autosomal recessive non-lethal form
      and a non-lethal autosomal dominant form with less severe radiographs
      manifestations and a better clinical outcome. Here, we report on clinical and
      radiological features of 19 novel MD patients. We describe new radiological
      features, including precocious calcification of hyoid and cricoid cartilage,
      irregular and squared-off calcaneal bones and severe hypoplasia of the anterior
      portion of first cervical vertebrae. In addition, the observation of an overlap
      between the autosomal recessive non-lethal form and the non-lethal autosomal
      dominant form, the rarity of sibship recurrences and the observation of vertical
      transmissions of MD in the literature argue in favor of an autosomal dominant
      mode of inheritance for all MD types. This hypothesis is reinforced by the use of
      the statistical single ascertainment method that rejects the hypothesis of an
      autosomal recessive mode of inheritance responsible for MD. Therefore, we propose
      that recurrence in sibs is due to gonadal mosaicism.

PMID- 18348258
TI  - Deletion of the first pair of fibronectin type III repeats of the integrin beta-4
      gene is associated with epidermolysis bullosa, pyloric atresia and aplasia cutis
      congenita in the original Carmi syndrome patients.

PMID- 18348259
TI  - Unique disease heritage of the Dutch-German Mennonite population.
AB  - The Dutch-German Mennonites are a religious isolate with foundational roots in
      the 16th century. A tradition of endogamy, large families, detailed genealogical
      records, and a unique disease history all contribute to making this a valuable
      population for genetic studies. Such studies in the Dutch-German Mennonite
      population have already contributed to the identification of the causative genes
      in several conditions such as the incomplete form of X-linked congenital
      stationary night blindness (CSNB2; previously iCSNB) and hypophosphatasia (HOPS),
      as well as the discovery of founder mutations within established disease genes
      (MYBPC1, CYP17alpha). The Dutch-German Mennonite population provides a strong
      resource for gene discovery and could lead to the identification of additional
      disease genes with relevance to the general population. In addition, further
      research developments should enhance delivery of clinical genetic services to
      this unique community. In the current review we discuss 31 genetic conditions,
      including 17 with identified gene mutations, within the Dutch-German Mennonite
      population.

PMID- 18348260
TI  - Duplication of chromosome band 12q24.11q24.23 results in apparent Noonan
      syndrome.
AB  - Noonan syndrome is an autosomal dominant disorder with an estimated incidence of
      1 in 1,000 to 1 in 2,500 live births. It is characterized by postnatal-onset
      short stature, characteristic facial changes, webbed neck, pectus carinatum, or
      excavatum, congenital heart defects, and bleeding abnormalities. Gain-of-function
      mutations in the PTPN11, KRAS, SOS1, and RAF1 genes that are components of the
      RAS/MEPK signaling pathway are identified in about 70-85% of individuals with
      Noonan syndrome. We report here a case of duplication of chromosome region
      12q24.11q24.23 identified by array comparative genomic hybridization (aCGH) that
      includes the PTPN11 gene in a 3-year-old girl with apparent Noonan syndrome. The
      patient presented with postnatal-onset failure-to-thrive, developmental delay,
      microcephaly, velopalatal incompetence, pectus excavatum, coarctation of aorta,
      atrial and ventricular septal defects, decreased muscle tone, and minor facial
      anomalies consistent with Noonan syndrome. At 3 years of age her speech, gross
      and fine motor development were at the level of a 12-18 month old child. This
      degree of developmental delay was atypical for an individual with Noonan
      syndrome, raising concerns for a chromosomal abnormality. Array-CGH showed an
      interstitial duplication of 10 Mb including the PTPN11 gene. Sequencing of
      PTPN11, KRAS, SOS1 and the coding region of RAF1 did not identify mutations. The
      increased gene dosage of the PTPN11 gene in the form of duplication is expected
      to have the same consequence as gain-of-function mutations seen in Noonan
      syndrome. We propose that at least some of the 15-30% of individuals with Noonan
      syndrome who do not have a mutation by sequencing may have a gain in copy number
      of PTPN11 and recommend that comprehensive testing for Noonan syndrome should
      include analysis for copy number changes of PTPN11.

PMID- 18348261
TI  - Highly variable cutis laxa resulting from a dominant splicing mutation of the
      elastin gene.
AB  - Autosomal dominant congenital cutis laxa (ADCL) is genetically heterogeneous and
      shows clinical variability. Only seven ADCL families with mutations in the
      elastin gene (ELN) have been described previously. We present morphological and
      molecular genetic studies in a cutis laxa kindred with a previously undescribed
      highly variable phenotype caused by a novel ELN mutation c.1621 C > T. The
      proband presented with severe cutis laxa, severe congenital lung disease
      previously undescribed in ADCL and pulmonary artery disease, which is often seen
      in ARCL but rare in ADCL. He also developed infantile spasms (OMIM 308350; West
      syndrome), which we consider a coincidental association although recessive cutis
      laxa or even digenic inheritance cannot be excluded. Electron microscopy of the
      proband's dermis revealed only mild rarefication of elastic fibers (in contrast
      to most recessive cutis laxa types). Apart from mild elastic fiber fragmentation,
      dermal morphology of the proband's father was within normal range. Molecular
      analysis of the ELN gene using genomic DNA from blood and RNA from cultured skin
      fibroblasts indicated a novel splice site mutation in the proband and his
      clinically healthy father. Analysis of ELN expression in fibroblasts provided
      evidence for a dominant-negative effect in the child, while due to an unknown
      mechanism, the father showed haploinsufficiency which might explain the
      significant clinical variability.

PMID- 18348262
TI  - Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients
      from Oman.
AB  - Excessive skin wrinkling and cutis laxa are seen in many genetic conditions and
      overlapping features can make a clinical diagnosis difficult. Here we report on
      22 Omani patients from 11 consanguineous families with the diagnosis of wrinkly
      skin syndrome (WSS, OMIM 278250) or geroderma osteodysplasticum hereditaria (GO,
      OMIM 231070). The WSS phenotype evolves during early childhood and includes a
      generalized and excessive skin wrinkling, dental problems, herniae, foot
      deformities, hip dislocations, growth retardation, and a large anterior
      fontanelle. The facial gestalt is characterized by a broad nasal bridge,
      hypertelorism, and downslanting palpebral fissures. We were unable to
      differentiate between WSS and cutis laxa with growth and developmental delay
      (CLGDD, OMIM 219200) suggesting that both can be considered as one entity.
      Distinct hallmarks of GO were skin wrinkling limited to the dorsum of hands and
      feet and to the abdomen, normal fontanelles, maxillary hypoplasia, bowed long
      bones, and osteopenia with frequent fractures. In contrast to the attenuation of
      the skin phenotype with age in WSS, adult patients with GO appeared prematurely
      aged. A serum sialotransferrin type 2 pattern was found in all four WSS patients
      tested. Apolipoprotein CIII (a marker for O-glycosylation) was normal suggesting
      that WSS is frequently associated with a N-protein glycosylation defect, probably
      at the level of processing (CDG-II). All four investigated GO patients showed
      normal sialotransferrin patterns. The known loci for cutis laxa and WSS on 2q31,
      5q23-q31, 7q11, 11q13, and 14q32 were excluded. We suggest that WSS and GO are
      distinct entities with overlapping features.

PMID- 18348263
TI  - PEDF from mouse mesenchymal stem cell secretome attracts fibroblasts.
AB  - Conditioned medium (secretome) derived from an enriched stem cell culture
      stimulates chemotaxis of human fibroblasts. These cells are classified as
      multipotent murine mesenchymal stromal cells (mMSC) by immunochemical analysis of
      marker proteins. Proteomic analysis of mMSC secretome identifies nineteen
      secreted proteins, including extracellular matrix structural proteins, collagen
      processing enzymes, pigment epithelium-derived factor (PEDF) and cystatin C.
      Immunodepletion and reconstitution experiments show that PEDF is the predominant
      fibroblast chemoattractant in the conditioned medium, and immunofluorescence
      microscopy shows strong staining for PEDF in the cytoplasm, at the cell surface,
      and in intercellular space between mMSCs. This stimulatory effect of PEDF on
      fibroblast chemotaxis is in contrast to the PEDF-mediated inhibition of
      endothelial cell migration, reported previously. These differential functional
      effects of PEDF toward fibroblasts and endothelial cells may serve to program an
      ordered temporal sequence of scaffold building followed by angiogenesis during
      wound healing.

PMID- 18348264
TI  - Differential regulation of mTOR-dependent S6 phosphorylation by muscarinic
      acetylcholine receptor subtypes.
AB  - Muscarinic receptors subserve many functions in both peripheral and central
      nervous systems. Some of these processes depend on increases in protein
      synthesis, which may be achieved by activation of mammalian target of rapamycin
      (mTOR), a kinase that regulates protein translation capacity. Here, we examined
      the regulation of mTOR-dependent signaling pathways by muscarinic receptors in SK
      N-SH human neuroblastoma cells, and in human embryonic kidney (HEK) cell lines
      transfected with individual muscarinic receptor subtypes. In SK-N-SH cells, the
      acetylcholine analog carbachol stimulated phosphorylation of the ribosomal S6
      protein, a downstream target of mTOR. The sensitivity of the response to subtype
      selective muscarinic receptor antagonists indicated that it was mediated by M3
      receptors. Carbachol-evoked S6 phosphorylation was blocked by the mTOR inhibitor
      rapamycin, but was independent of phosphoinositide 3-kinase activation. The
      response was significantly reduced by the mitogen-activated protein kinase kinase
      (MEK) inhibitor U0126, which also inhibited carbachol-evoked S6 phosphorylation
      in HEK cells expressing M2 receptors, but was ineffective in M3 receptor
      expressing HEK cells, although carbachol activated MAPK in both transfected
      lines. The p90 ribosomal S6 kinase has been implicated in mTOR regulation by
      phorbol esters, but was not activated by carbachol in any of the cell lines
      tested. The protein kinase C inhibitor bisindolylmaleimide I reduced carbachol
      stimulated S6 phosphorylation in SK-N-SH cells, and in HEK cells expressing M3
      receptors, but not in HEK cells expressing M2 receptors. The results demonstrate
      that multiple muscarinic receptor subtypes regulate mTOR, and that both MAPK
      dependent and -independent mechanisms may mediate the response in a cell context
      specific manner.

PMID- 18348265
TI  - Selective inhibition of cyclooxygenase-2 (COX-2) by 1alpha,25-dihydroxy-16-ene-23
      yne-vitamin D3, a less calcemic vitamin D analog.
AB  - Inducible cyclooxygenase-2 (COX-2) has been implicated to play a role in
      inflammation and carcinogenesis and selective COX-2 inhibitors have been
      considered as anti-inflammatory and cancer chemopreventive agents. 1alpha,25
      dihydroxyvitamin D3 (1alpha,25(OH)2D3), the active hormonal form of vitamin D3
      also has been considered to be a cancer chemopreventive agent in addition to its
      important role in maintaining calcium homeostasis. Based on these observations,
      we studied the direct effect of 1alpha,25(OH)2D3 and one of its less calcemic
      synthetic analogs, 1alpha,25(OH)2-16-ene-23-yne-D3 on the activity of both COX-1
      and COX-2 in an in vitro enzyme assay. Preliminary data indicated that both
      1alpha,25(OH)2D3 and 1alpha,25(OH)2-16-ene-23-yne-D3 inhibited selectively the
      activity of COX-2 with no effect on the activity of COX-1. Out of the two
      compounds, 1alpha,25(OH)2-16-ene-23-yne-D3 was found to be more effective with an
      IC50 of 5.8 nM. Therefore, the rest of the experiments were performed using
      1alpha,25(OH)2-16-ene-23-yne-D3 only. 1alpha,25(OH)2-16-ene-23-yne-D3 inhibited
      the proliferation of lipopolysaccharide (LPS) stimulated mouse macrophage cells
      (RAW 264.7) with a reduction in the expression of COX-2 along with other
      inflammatory mediators like inducible nitric oxide synthase (iNOS) and
      interleukin-2 (IL-2). Furthermore, 1alpha,25(OH)2-16-ene-23-yne-D3 also inhibited
      carrageenan induced inflammation in an air pouch of a rat and effectively reduced
      the expression of COX-2, iNOS, and IL-2 in the tissues of the same air pouch. In
      both cases, 1alpha,25(OH)2-16-ene-23-yne-D3 did not show any effect on the
      expression of COX-1. In summary, our results indicate that 1alpha,25(OH)2-16-ene
      23-yne-D3, a less calcemic vitamin D analog, exhibits potent anti-inflammatory
      effects and is a selective COX-2 inhibitor.

PMID- 18348266
TI  - Clinical genetics and the Hutterite population: a review of Mendelian disorders.
AB  - The Hutterian Bretheren is an isolated population living on the North American
      prairies, the current community exceeding 40,000 in number. Their unique genetic
      history has contributed to a founder effect, which is reflected in the Mendelian
      disorders present in this population today. Genetic studies in the Hutterite
      population have led to the identification of a number of genes over the last
      several years and highlights the power of this population for gene
      identification. However, for the more than 30 autosomal recessive conditions
      currently recognized in this population, the gene or Hutterite specific mutation
      remains to be identified for over half and novel autosomal recessive syndromes
      continue to be recognized. This review summarizes what is currently understood
      about the molecular etiology of the Mendelian disorders and highlights the
      cardinal features of those disorders that are unique to or over-represented in
      this population.

PMID- 18348267
TI  - A de novo SOX10 mutation causing severe type 4 Waardenburg syndrome without
      Hirschsprung disease.
AB  - Type 4 Waardenburg syndrome represents a well define entity caused by neural
      crest derivatives anomalies (melanocytes, intrinsic ganglion cells, central,
      autonomous and peripheral nervous systems) leading, with variable expressivity,
      to pigmentary anomalies, deafness, mental retardation, peripheral neuropathy, and
      Hirschsprung disease. Autosomal dominant mode of inheritance is prevalent when
      Sox10 gene mutation is identified. We report the natural history of a child who
      presented with synophrys, vivid blue eye, deafness, bilateral complete
      semicircular canals agenesis with mental retardation, subtle signs for peripheral
      neuropathy and lack of Hirschsprung disease. SOX10 gene sequencing identified "de
      novo" splice site mutation (c.698-2A > C). The present phenotype and the genotype
      findings underline the wide spectrum of SOX10 gene implication in unusual type 4
      Waardenburg syndrome patient.

PMID- 18348268
TI  - Clinical and molecular analysis of arylsulfatase E in patients with
      brachytelephalangic chondrodysplasia punctata.
AB  - X-linked Recessive Chondrodysplasia Punctata (CDPX1) is due to a defect in
      arylsulfatase E (ARSE), located on Xp22.3. Neither the substrate nor function of
      the encoded warfarin-sensitive arylsulfatase has been identified and molecular
      analysis remains the only confirmatory diagnostic test. Nevertheless, the
      majority of patients evaluated have not had identifiable mutations in ARSE, and
      thus far 23 patients have been reported. The major clinical features in these
      patients are also present in a group now recognized as phenocopies, due to
      vitamin K deficiency in early gestation or maternal autoimmune disease. We
      evaluated the ARSE gene in 11 patients who met clinical criteria for CDPX1. We
      amplified all exons and intronic flanking sequence from each patient, and
      investigated suspected deletions or rearrangements by southern analysis. We
      identified mutations in seven individuals. Of the remainder, three had maternal
      conditions that further expand the phenocopy group. Thus, this group might
      represent a proportion of the mutation-negative patients in previous studies. We
      extracted clinical information from all prior reports over the past decade and
      show that there are few distinguishing features on examination between these two
      groups of patients. This study supports heterogeneity for CDPX1-like phenotypes
      and sorting these out will help to define the biological pathway and genetic
      contributors.

PMID- 18348269
TI  - Hardikar syndrome: long term outcome of a rare genetic disorder.
AB  - Hardikar syndrome is a rare disorder of unknown etiology. Features of the
      syndrome are manifold with a predominance of liver and renal involvement. The
      syndrome is clearly distinct from other previously described syndromes such as
      Alagille syndrome, congenital hepatic fibrosis, Caroli disease, and Kabuki make
      up syndrome. To date, only four cases of Hardikar syndrome have been published
      worldwide. We report here on the long term outcome of these patients.

PMID- 18348270
TI  - Delineation of the phenotype associated with 7q36.1q36.2 deletion: long QT
      syndrome, renal hypoplasia and mental retardation.
AB  - Terminal deletions of the long arm of chromosome 7 are well known and are
      frequently associated with hypotelorism or holoprosencephaly due to the
      involvement of the SHH gene located in 7q36.3. These deletions are easily
      detectable with routine subtelomeric MLPA analysis. Deletions affecting a more
      proximal part of 7q36, namely bands 7q36.1q36.2 are less common, and may be
      missed by subtelomeric MLPA analysis. We report a 9-year-old girl with a 5.27 Mb
      deletion in 7q36.1q36.2, and compare her to literature patients proposing a
      phenotype characterized by mental retardation, unusual facial features, renal
      hypoplasia and long QT syndrome due to loss of the KCNH2 gene. These
      characteristics are sufficiently distinct that the syndrome may be diagnosed on
      clinical grounds.

PMID- 18348271
TI  - An undiagnosed cytogenetic abnormality results in the misidentification of a
      Duchenne muscular dystrophy carrier.

PMID- 18348272
TI  - Association of homozygous LMNA mutation R471C with new phenotype: mandibuloacral
      dysplasia, progeria, and rigid spine muscular dystrophy.
AB  - We report on a 7-year-old girl with a phenotype combining mandibuloacral
      dysplasia (MAD), progeria, and rigid spine muscular dystrophy. Mild proximal
      weakness, contractures, and rigidity of the spine were the primary findings.
      Although present since birth, dysmorphic manifestations typical for MAD and
      progeroid features became more prominent with time, and the full clinical
      phenotype was recognizable at early school age. Her phenotype was caused by a
      homozygous mutation in LMNA (c.1411C > T, which predicts p.R471C) inherited from
      the heterozygous, consanguineous, unaffected parents. This mutation has only been
      reported in compound heterozygous state and was associated with a milder
      phenotype. Some LMNA mutations are known to cause MAD and overlapping phenotypes
      (MAD spectrum) in an autosomal recessive pattern. The p.R471C homozygous LMNA
      mutation causes a severe phenotype of the MAD spectrum. This case extends the
      clinical spectrum of MAD and further expands the phenotypic range of lamin A/C
      associated diseases.

PMID- 18348273
TI  - A novel nonsense mutation in MYO6 is associated with progressive nonsyndromic
      hearing loss in a Danish DFNA22 family.
AB  - Autosomal dominant inheritance is described in about 20% of all nonsyndromic
      hearing loss with currently 54 distinct loci (DFNA1-54), and >20 different genes
      identified. Seven different unconventional myosin genes are involved in ten
      different types of syndromic and nonsyndromic hearing loss with different
      patterns of inheritance: MYO7A in DFNA11/DFNB2/USH1B, MYH9 in DFNA17, MYH14 in
      DFNA4, MYO6 in DFNA22/DFNB37, MYO3A in DFNB30, MYO1A in DFNA48, and MYO15A in
      DFNB3. Two missense mutations in MYO6 (p.C442Y and p.H246R) have been
      characterized in families of Italian and American Caucasian extraction with
      autosomal dominant hearing loss, respectively, and the latter was associated with
      cardiomyopathy in some patients. Three Pakistani families had homozygosity for
      three MYO6 mutations (c.36insT, p.R1166X, and p.E216V, respectively), and was in
      one instance associated with retinal degeneration. In the present study, we
      linked autosomal dominant hearing loss in a large Danish family to a 38.9 Mb
      interval overlapping with the DFNA22/DFNB37 locus on chromosome 6q13. A novel
      nonsense mutation in MYO6 exon 25 (c.2545C > T; p.R849X) was identified in the
      family. The mutation co-segregated with the disease and the mutant allele is
      predicted to encode a truncated protein lacking the coiled-coil and globular tail
      domains. These domains are hypothesized to be essential for targeting myosin VI
      to its cellular compartments. No other system was involved indicating
      nonsyndromic loss. In conclusion, a novel nonsense MYO6 mutation causes post
      lingual, slowly progressive autosomal dominant nonsyndromic moderate to severe
      hearing loss in a Danish family.

PMID- 18348274
TI  - A de novo missense mutation in the gene encoding the SOX10 transcription factor
      in a Spanish sporadic case of Waardenburg syndrome type IV.

PMID- 18348275
TI  - Expanded clinical phenotype of women with the FMR1 premutation.
AB  - Fragile X-associated tremor/ataxia syndrome (FXTAS) is generally considered to be
      uncommon in older female carriers of premutation alleles (55-200 CGG repeats) of
      the fragile X mental retardation 1 (FMR1) gene; however, neither prevalence, nor
      the nature of the clinical phenotype, has been well characterized in female
      carriers. In this study, we evaluated 146 female carriers (mean, 42.3 years;
      range, 20-75 years) with and without core features of FXTAS (tremor; gait
      ataxia), and 69 age-matched controls (mean, 45.8 years; range, 21-78 years).
      Compared with controls, carriers with definite or probable FXTAS had greater
      medical co-morbidity, with increased prevalence of thyroid disease (P = 0.0096),
      hypertension (P = 0.0020), seizures (P = 0.0077), peripheral neuropathy (P =
      0.0040), and fibromyalgia (P = 0.0097), in addition to the typical symptoms of
      FXTAS-tremor (P < 0.0001) and ataxia (P < 0.0001). The non-FXTAS premutation
      group had more complaints of chronic muscle pain (P = 0.0097), persistent
      paraesthesias in extremities (P < 0.0001), and history of tremor (P < 0.0123)
      than controls. The spectrum of clinical involvement in female carriers with FXTAS
      is quite broad, encompassing a number of medical co-morbidities as well as the
      core movement disorder. The remarkable degree of thyroid dysfunction (17% in the
      non-FXTAS group and 50% in the FXTAS group) warrants consideration of thyroid
      function studies in all female premutation carriers, particularly those with core
      features of FXTAS.

PMID- 18348276
TI  - Trisomies 13 and 18: population prevalences, characteristics, and prenatal
      diagnosis, metropolitan Atlanta, 1994-2003.
AB  - In recent years, prenatal diagnosis and elective pregnancy termination have
      affected the reported birth prevalence of trisomies 13 and 18. We examined the
      prevalence and characteristics of these conditions using 1994-2003 data from a
      population-based surveillance system, the Metropolitan Atlanta Congenital Defects
      Program. Including fetal deaths and elective terminations increased the number of
      affected pregnancies by 58.7% for trisomy 13 and 72.2% for trisomy 18. Prenatal
      cytogenetic testing was reported in 70.8% of trisomy 13 cases and 76.1% of
      trisomy 18 cases. Among those with prenatal cytogenetic tests, 60.8% of trisomy
      13 and 59.7% of trisomy 18 cases were electively terminated. Compared with non
      Hispanic whites, non-Hispanic black race was associated with a decreased
      frequency of prenatal cytogenetic testing for both trisomy 13 and trisomy 18 (OR
      0.24, 95% CI: 0.08-0.78 and OR 0.32, 95% CI: 0.14-0.69, respectively). The
      reported rates of prenatal cytogenetic testing remained stable throughout the
      period. As expected, maternal age > or =35 years was a risk factor for both
      conditions. However, while 67.1% (n = 55) of the trisomy 18 case mothers were >
      or =35 years, only 46.9% (n = 15) of the trisomy 13 case mothers were > or =35
      years. Among live-born infants, the sex ratio among trisomy 18 infants showed an
      increased proportion of females: 60.4% female versus 39.6% male. However, the
      proportion was 48.3% female and 51.7% male among fetuses that were electively
      terminated in the second trimester. Inclusion of pregnancies that are prenatally
      diagnosed is critical for accurate surveillance and population-based analyses of
      these conditions.

PMID- 18348277
TI  - Single nucleotide polymorphisms in the cadherin 23 (CDH23) gene in Polish workers
      exposed to industrial noise.
AB  - Single nucleotide polymorphisms (SNPs) are the most frequent type of variation in
      the human genome and may underlie differential susceptibility to common genetic
      diseases. A candidate gene for susceptibility to noise-induced hearing loss
      (NIHL) is Cadherin 23 (CDH23). This study aimed to analyze genetic variation in
      the CDH23 gene in a group of 10 individuals derived from a cohort of 949 workers
      exposed to noise, and consisted of five persons from each of the resistant and
      susceptible extremes. DNA samples were collected and the coding exons of CDH23
      were sequenced. We identified a total of 35 SNPs: 11 amino acid substitutions, 8
      silent nucleotide changes, and 16 substitutions in intervening sequences. Ten of
      the 11 amino acid substitutions were previously shown also to segregate in a
      Cuban population. The nonsynonymous SNPs localized to the part of the gene
      encoding the extracellular domain of Cadherin 23, in particular ectodomains 5,
      13, 14, 15, 16, 17, 19, and 22. One amino acid change occurred at a conserved
      position in ectodomain 5. Our results provide a framework for future study of
      polymorphisms in CDH23 as risk factor for NIHL.

PMID- 18348278
TI  - Insights into the ethnic differences in serum ferritin between black and white US
      adult men.
AB  - Although higher serum ferritin (SF) concentrations have been consistently
      observed among blacks, despite their lower hemoglobin (Hb) concentrations
      compared with whites, few studies attempted to explain this SF difference. To
      determine the possible factors contributing to the observed SF difference between
      blacks and whites, 1,938 non-Hispanic white (NHW) and 1,616 non-Hispanic black
      (NHB) male subjects, aged 20-65 years were selected from the third National
      Health and Nutrition Examination Survey (NHANES III). Multiple regression
      analysis was used to examine the contribution of dietary, biochemical, and
      socioeconomic variables to the observed SF difference between the two groups. NHB
      subjects showed a continuing, significantly higher SF concentration compared with
      NHW subjects at each age group. Age, serum total protein, mean cell volume (MCV),
      and gamma glutamyl transferase (GGT) were positively associated with SF, whereas
      percent energy from carbohydrate and fat, calcium intake, serum alpha-carotene,
      and iron binding capacity (TIBC) were inversely associated with SF (P < 0.01).
      After excluding subjects with abnormal serum total protein, TIBC and GGT levels
      from the analysis (the final regression model), the SF difference dropped to 3.95
      microg/l (initial difference = 37.1 microg/l) between NHWs and NHBs. The results
      suggest that the oft-noted black-white SF difference is a result of factors
      including overall nutrition and health, iron status, and hepatic well-being.
      Higher SF, low Hb, and reduced TIBC level observed in blacks are consistent with
      the definition of anemia of chronic disease (ACD). Future investigations are
      needed to confirm the role of ACD in the black-white SF difference.

PMID- 18348279
TI  - CBF/NF-Y controls endoplasmic reticulum stress induced transcription through
      recruitment of both ATF6(N) and TBP.
AB  - Previously the analysis of promoters regulated by endoplasmic reticulum (ER)
      stress identified a composite promoter element, ERSE that interacts with both
      CBF/NF-Y (CBF) and ATF6(N) transcription factors. This prompted us to investigate
      the underlying mechanism by which CBF, a ubiquitously binding transcription
      factor, specifically controls transcription activation during ER stress. The in
      vitro DNA binding study performed using purified recombinant proteins revealed
      that CBF specifically recruits ATF6(N) to ERSE DNA but it does not interact with
      ATF6(N) in absence of DNA binding. Inhibition of CBF binding resulted in a
      significant reduction of optimal transcription activation of cellular genes
      during ER stress. Analysis of cellular promoters by ChIP demonstrated that CBF is
      needed for recruitment of both ATF6(N) and TBP but not for either acetylation of
      histone H3-K9 or trimethylation of histone H3-K4 during ER stress. Together these
      study results reveal that CBF controls ER stress-inducible transcription through
      recruitment of both ATF6(N) and TBP but not through chromatin modifications. Our
      observations are in agreement with the results of recently published studies that
      have shown that CBF controls transcription of varieties of inducible promoters
      through recruitment of general transcription factors but not through acetylation
      of histone H4. These findings provide a paradigm of the function of CBF in
      inducible transcription.

PMID- 18348280
TI  - Importance of autophosphorylation at Ser186 in the A-loop of salt inducible
      kinase 1 for its sustained kinase activity.
AB  - Autophosphorylation is an important mechanism by which protein kinases regulate
      their own biological activities. Salt inducible kinase 1 (SIK1) is a regulator in
      the feedback cascades of cAMP-mediated gene expression, while its kinase domain
      also features autophosphorylation activity. We provide evidence that Ser186 in
      the activation loop is the site of autophosphorylation and essential for the
      kinase activity. Ser186 is located at the +4 position of the critical Thr residue
      Thr182, which is phosphorylated by upstream kinases such as LKB1. The
      relationship between phosphorylation at Ser186 and at Thr182 in COS-7 cells
      indicates that the former is a prerequisite for the latter. Glycogen synthase
      kinase-3beta (GSK-3beta) phosphorylates Ser/Thr residues located at the fourth
      position ahead of the pre-phosphorylated Ser/Thr residues, and inhibitors of GSK
      3beta reduce the phosphorylation at Thr182. The results of an in vitro
      reconstitution assay also indicate that GSK-3beta could be the SIK1 kinase.
      However, overexpression and knockdown of GSK-3beta in LKB1-defective HeLa cells
      suggests that GSK-3beta alone may not be able to phosphorylate or activate SIK1,
      indicating that LKB1 may play a crucial role by phosphorylating SIK1 at Thr182,
      possibly as an initiator of the autophosphorylation cascade, and GSK-3beta may
      phosphorylate SIK1 at Thr182 by recognizing the priming-autophosphorylation at
      Ser186 in cultured cells. This may also be the case for the other isoform SIK2,
      but not for SIK3.

PMID- 18348281
TI  - Dialectical behavior therapy for clients with binge-eating disorder or bulimia
      nervosa and borderline personality disorder.
AB  - OBJECTIVE: This treatment development study provides summary data for standard
      Dialectical Behavior Therapy (DBT) with minimal adaptation for 8 women with binge
      eating disorder (BED) (5) or bulimia nervosa (BN) (3) and Borderline Personality
      Disorder (BPD). METHOD: DBT involved 6 months of weekly skills group, individual
      DBT, therapist consultation team meeting, and 24-hour telephone coaching.
      Assessments were conducted at pre-, post-treatment, and 6-months follow-up and
      utilized standardized clinical interviews including the Eating Disorders
      Examination (EDE), Personality Disorders Exam, and the Structured Clinical
      Interview for DSM-IV. RESULTS: From pre- to post-treatment, effect sizes for
      objective binge eating, total EDE scores and global adjustment were large and for
      number of non-eating disorder axis I disorders and for suicidal behavior and self
      injury were medium. From pre- to 6-months follow-up, effect sizes were large for
      all these outcomes. CONCLUSION: This provides promising pilot data for larger
      studies utilizing DBT for BED or BN and BPD.

PMID- 18348282
TI  - Anorexia nervosa: selective processing of food-related word and pictorial stimuli
      in recognition and free recall tests.
AB  - OBJECTIVE: Maladaptive processing of food cues is considered pivotal in the
      psychopathology of anorexia nervosa. However, the influence of hunger and
      differences in processing because of the type of stimuli remain largely unclear.
      METHOD: Memory bias for food-related pictorial and semantic stimuli was assessed
      in a recognition and a free recall test in 16 anorexia nervosa (AN) patients, 16
      control participants with food intake prior to the study (CG-FI) and 16 control
      participants with a fasting period prior to the study (CG-NF). RESULTS: Compared
      with CG-FI participants, both AN and CG-NF participants responded faster to food
      related as compared with neutral words (p < .001) in the recognition test.
      Differences were found for word but not for pictorial stimuli. No group
      differences were observed with respect to the number of correct retrievals in
      either the recognition or the free recall test. CONCLUSION: The present study
      found behavioral indications of abnormal processing of food-related and neutral
      stimuli in anorectic patients similar to those found in fasted healthy controls.
      Results are discussed in terms of self-schemata in eating disorders, competitive
      interference, and levels of processing.

PMID- 18348283
TI  - Disordered eating and substance use in high-school students: results from the
      Youth Risk Behavior Surveillance System.
AB  - OBJECTIVE: To examine the association between disordered eating (fasting, diet
      product use, and vomiting or laxative use) and use of 10 substances (cigarettes,
      alcohol, marijuana, cocaine, inhalants, heroin, methamphetamines, ecstasy,
      steroids, and hallucinogens) in a nationally representative adolescent sample.
      METHOD: Participants were 13,917 U.S. high-school students participating in the
      2005 Youth Risk Behavior Surveillance System. RESULTS: Disordered eating was
      significantly associated with the use of each substance. Using effect size
      estimates that take base rates into consideration, for female students,
      associations between substance use and disordered eating were weak for all but
      three forms of substance use: current smoking, binge drinking, and inhalants.
      Among male students, strong (marijuana, steroids, and inhalants) or moderate
      effects (all other substances) were observed. CONCLUSION: Future research needs
      to focus on inhalant use and methamphetamine use in males. Increased medical
      attention should be directed toward adolescents who practice disordered eating
      behaviors because they are also at elevated risk for using cigarettes, alcohol,
      inhalants, methamphetamines, and steroids.

PMID- 18348284
TI  - Expression and activity of P-glycoprotein (MDR1/ABCB1) in peripheral blood
      mononuclear cells from patients with anorexia nervosa compared with healthy
      controls.
AB  - OBJECTIVE: Pharmacotherapeutic strategies for treatment of anorexia nervosa (AN)
      are characterized by limited success. Some drugs used (antipsychotics, selective
      serotonin reuptake inhibitors) are transported by P-glycoprotein (P-gp), a
      transporter with major impact on pharmacokinetics of substrate drugs. Biochemical
      alterations seen in AN patients could lead to increased expression and/or
      activity of P-gp and therefore to diminished access of drugs to the brain. The
      aim of our study was to investigate expression and activity levels of P-gp in
      peripheral blood mononuclear cells (PBMCs) in AN patients. METHOD: PBMCs of 16 AN
      patients and 16 controls were isolated. Activity of P-gp was determined by flow
      cytometry and expression was quantified by reverse-transcriptase-real-time
      polymerase-chain-reaction. RESULTS: Neither a significant difference in P-gp
      expression (AN: 0.00154 +/- 0.00088 [MDR1/beta2 mg], control: 0.00244 +/- 0.0013
      [MDR1/beta2 mg], p = .138) nor a difference in P-gp activity (rhodamine 123 ratio
      AN: 1.79 +/- 0.73, control: 2.03 +/- 0.42, p = .20) between AN patients and
      healthy controls could be detected. In contrast to previous studies, expression
      and activity of P-gp correlated significantly (p = .0031). CONCLUSION: Failure in
      pharmacotherapy with P-gp substrates in AN patients are probably neither caused
      by different P-gp expression nor activity levels.

PMID- 18348285
TI  - Identification and characterization of the unique guanine nucleotide exchange
      factor, SmgGDS, in vascular smooth muscle cells.
AB  - The guanine nucleotide exchange factor (GEF), SmgGDS, promotes nucleotide
      exchange by several GTPases in both the Ras and Rho families, especially by RhoA.
      Because RhoA plays an important role in regulating the contraction of vascular
      smooth muscle cells (VSMC), we examined the expression and function of SmgGDS in
      VSMC. SmgGDS is expressed in primary rat aortic smooth muscle (ASM) cells,
      primary bovine coronary artery smooth muscle (BCASM) cells, and the immortalized
      A7r5 line of rat ASM cells. Down regulation of SmgGDS expression by siRNA
      transfection resulted in a decrease of RhoA-GTP levels, enhanced cell spreading,
      and loss of the characteristic elongated morphology of VSMC. A similar morphology
      was also observed following treatment with the Rho-kinase inhibitor, Y27632. In
      contrast, cells with reduced RhoA expression exhibit an elongated shape.
      Subsequent immunofluorescent staining revealed a disruption of the myosin
      filament organization in the cells with reduced SmgGDS expression. Further
      studies analyzed the effect of SmgGDS siRNA transfection on the contraction of
      A7r5 cells and BCASM cells, which is also a Rho-regulated pathway. Transfection
      of SmgGDS siRNA or RhoA siRNA resulted in an impaired ability of the A7r5 and
      BCASM cells to undergo contraction in a collagen gel matrix. However,
      phosphorylation of the myosin-binding subunit of myosin phosphatase (MYPT1) or
      the light chain of myosin II (MLC) was not altered by downregulating expression
      of either SmgGDS or RhoA GTPase. Taken together these results identify SmgGDS as
      a novel regulator of myosin organization and contraction in VSMC.

PMID- 18348286
TI  - High-throughput amplicon scanning of the TP53 gene in breast cancer using high
      resolution fluorescent melting curve analyses and automatic mutation calling.
AB  - Identifying mutations in the TP53 gene is important for cancer prognosis,
      predicting response to therapy, and determining genetic risk. We have developed a
      high-throughput scanning assay with automatic calling to detect TP53 mutations in
      DNA from fresh frozen (FF) and formalin-fixed paraffin-embedded (FFPE) tissues.
      The coding region of the TP53 gene (exons 2-11) was PCR-amplified from breast
      cancer samples and scanned by high-resolution fluorescent melting curve analyses
      using a 384-well format in the LightCycler 480 instrument. Mutations were
      confirmed by direct sequencing. Sensitivity and specificity of scanning and
      automatic mutation calling was determined for FF tissue (whole genome amplified
      [WGA] and non-WGA) and FFPE tissue. Thresholds for automatic mutation calling
      were established for each preparation type. Overall, we confirmed 27 TP53
      mutations in 68 primary breast cancers analyzed by high-resolution melting curve
      scanning and direct sequencing. Using scanning and automatic calling, there was
      high specificity (>95%) across all DNA preparation methods. Sensitivities ranged
      from 100% in non-WGA DNA from fresh tissue to 86% in WGA DNA and DNA from
      formalin-fixed, paraffin-embedded tissue. Scanning could detect mutated DNA at a
      dilution of 1:200 in a background of wild-type DNA. Mutation scanning by high
      resolution fluorescent melting curve analyses can be done in a high-throughput
      and automated fashion. The TP53 scanning assay can be performed from a variety of
      specimen types with high sensitivity/specificity and could be used for clinical
      and research purposes.

PMID- 18348287
TI  - Large scale DNA sequencing: new challenges emerge--the 2007 Human Genome
      Variation Society scientific meeting.
AB  - The annual scientific meeting of the Human Genome Variation Society (HGVS) was
      held on 23 October 2007, in San Diego, CA. The major theme of this meeting was
      "New DNA Sequencing Technologies & Human Genome Variation." A series of speakers
      provided information on several new technologies that produce DNA sequence data
      on a scale far beyond what was possible even a few years ago. These new
      technologies produce up to gigabases of nucleotides on a single run. Already, two
      individuals have had their entire genome sequenced, resulting in the
      identification of many novel DNA variants. Several new questions now need to be
      answered. What impact do these novel variants have on the phenotypes? How are we
      to associate private variants in a single individual with disease, especially
      when current association studies require genotyping thousands of individuals?
      Further work will be required to create methodologies to analyze these variants
      to determine if they are potentially disease-producing or are phenotypically
      silent. For the technology to be useful in a medical setting it will be crucial
      to answer to these questions.

PMID- 18348288
TI  - Animal farm: do our four-legged friends hold the answer to inflammatory bowel
      disease?

PMID- 18348289
TI  - Integrated DNA, cDNA, and protein studies in Becker muscular dystrophy show high
      exception to the reading frame rule.
AB  - Becker muscular dystrophy (BMD) is a milder form of X-linked Duchenne muscular
      dystrophy (DMD). Here, we report a study of 75 patients with immunoblot and/or
      immunostaining findings of muscle biopsy consistent with BMD (abnormal
      dystrophin). We utilized multiplex ligation dependent probe amplification (MLPA)
      on genomic DNA (gDNA) to screen all 79 exons for both deletions and duplications.
      A total of 19 patients testing negative for MLPA mutations were tested for mRNA
      splicing abnormalities using cDNA-MLPA on muscle biopsy. Complete cDNA sequencing
      was done on MLPA-negative patients. We identified disease-causing mutations in 66
      (88%) of the patients. Of the mutation-positive patients, 42 (64%) showed
      deletions of one or more exons, 14 (21%) showed duplications, and 10 (15%) showed
      various mutations detected by cDNA-MLPA and sequencing studies. We found a high
      rate of "exceptions" to the reading frame rule in this BMD series (out-of-frame
      BMD; 17/56 deletions/duplications; 30%). This was partly explained by the high
      incidence of 5' gene deletions in BMD patients (a region known to be a hotspot
      for exceptions), and due to complex splicing patterns in which a subset of
      transcripts showed deletions larger than gDNA (exon-skipping). Comparing our
      findings in BMD to previously published DMD data, BMD patients have higher
      proportions of duplications, a different distribution of mutations, and higher
      exception to the reading frame rule.

PMID- 18348290
TI  - Oral administration of cyanobacterial bloom extract induced the altered
      expression of the PP2A, Bax, and Bcl-2 in mice.
AB  - The frequent occurrences of the toxic cyanobacterial (specifically Microcystis
      aeruginosa) bloom are becoming a global environmental issue. Lots of researches
      have been focused on the pure cyanobacterial toxins, but little on the natural
      cyanobacterial bloom. This study was undertaken to investigate the effect of the
      natural cyanobacterial bloom extract on the expression of proteins, which have
      been shown to be affected by pure microcystins. In current study, the
      cyanobacterial bloom extract has been administered orally to ICR mice for 7 days
      with different dosages. The expression level of PP2A, Bcl-2, and Bax was measured
      via western blotting. The results showed that after 7 days of exposure to
      cyanobacteria extract, in mice liver tissue, the expression level of PP2A and Bax
      was increased significantly between the control and treatment groups, but there
      is no significant change on the Bcl-2 expression. This is the first report to
      describe the altered expression of PP2A in vivo when mice exposure to natural
      water blooms extract that means many cellular pathways would be interfered via
      the change of PP2A activity.

PMID- 18348291
TI  - Effects of 2,4-dichlorophenol on the expression of vitellogenin and estrogen
      receptor genes and physiology impairments in Chinese rare minnow (Gobiocypris
      rarus).
AB  - 2,4-Dichlorophenol (2,4-DCP) is known as a toxicant, but unknown as an
      environmental endocrine disruptor. In the present work, Chinese rare minnow
      (Gobiocypris rarus) was exposed to 0.03, 0.3, and 3 mg/L 2,4-DCP for 3 d and 0.1,
      0.3, and 1 mg/L 2,4-DCP for 21 d, respectively. Endpoints including somatic
      index, vitellogenin (VTG) mRNA and protein level, estrogen receptor (ER) mRNA and
      histopathology were measured. In the 3-d exposure experiment, the effect
      concentrations were 0.3 mg/L and above, and in 21-d exposure, the effect
      concentrations were 0.1 mg/L and above. When exposed to the effect
      concentrations, GSI was significantly reduced for both male and female, ER mRNA
      was upregulated in male and downregulated in female. There were no significant
      variations of VTG mRNA in both male and female in 3-d exposure and in male in 21
      d exposure. However, VTG mRNA in female in 21-d exposure was upregulated,
      corresponding to an increase of VTG protein in serum. Histopathological
      observation showed that ovaries were degenerated in the effect concentrations,
      where follicular atresias were more frequently observed. Because the sex hormones
      related genes and toxicological endpoints were affected in the dose-dependent
      manner, the results suggest that 2,4-DCP could be a potential endocrine disruptor
      and might cause adverse effects in female sex organs through interruption of ER
      mediated processes.

PMID- 18348292
TI  - Oxygen decline in biotesting of environmental samples--is there a need for
      consideration in the acute zebrafish embryo assay?
AB  - Environmental samples such as groundwater, sediment pore water, native or freeze
      dried sediments may be difficult to analyze for toxic effects with organismic
      aquatic bioassays. These samples might evoke low oxygen concentration or oxygen
      depletion during the test. The toxicity assessment could thus be confounded by
      low oxygen concentrations. The acute zebrafish embryo assay was used to analyze
      the influence of oxygen deficit on the embryonic development in the first 48 h
      post fertilization. Embryos were exposed to varying oxygen concentrations ranging
      from <30 to >80% oxygen saturation of water. A clear concentration dependent
      retardation of fish embryo development was observed. Because of a retarded
      development toxic thresholds of environmental samples which might include
      substances slowing down the development will be altered. For the purpose of
      identification of critical contaminants in complex environmental samples, it is
      proposed to actively aerate environmental samples which are likely to be oxygen
      depleted during the duration of the zebrafish embryo bioassay.

PMID- 18348293
TI  - Combined effect of ultraviolet-B radiation and cadmium contamination on nutrient
      uptake and photosynthetic pigments in Brassica campestris L. seedlings.
AB  - Environmental and industrial pollution along with increase in ground level UV-B
      radiation, because of stratospheric ozone depletion, present multiple stresses,
      which may affect crop photosynthesis and productivity. The present study was
      undertaken to see interactive effects of heavy metal contamination (Cd(2+)) and
      UV-B exposure on essential nutrient (Ca(2+), Mg(2+), K(+)) uptake, biomass, and
      chlorophyll content in mustard (Brassica campestris L.) seedlings. Plants grown
      in 0.5, 1.0, 2.5, and 5.0 mg L(-1) Cd(2+) supplemented medium were exposed to UV
      B for 30 min (0.4 mW cm(-2)) per day. The interactive effect of two stresses
      measured after 5 and 10 days showed an overall decline in biomass. Under dual
      stress (5 mg Cd(2+) L(-1)) significant (P < 0.001) decrease in chlorophyll a
      (43%), chlorophyll b (23%), and carotenoid (53%) was observed. Ca(2+) uptake was
      reduced by 51% in roots under high doses of Cd(2+) (5 mg L(-1)) and simultaneous
      exposure to 0.4 mW cm(-2) UV-B for 10 days. Mg(2+) content was reduced by 48% and
      K(+) by 62% under similar exposure conditions. Decline in nutrient uptake in
      Brassica campestris L. seedlings was observed both in root and shoot leaf in the
      initial growth period under controlled lab conditions. Cadmium ion (Cd(2+))
      uptake was significantly enhanced by 33% (P < 0.001) in the presence of UV-B. The
      findings are significant as multiple stress conditions prevalent in the
      environment play an important role during the early growth period, a period
      critical for crop yield.

PMID- 18348294
TI  - Molecular monitoring in chronic myeloid leukemia: response to tyrosine kinase
      inhibitors and prognostic implications.
AB  - The majority of patients with chronic-phase (CP) chronic myeloid leukemia (CML)
      who are treated with Bcr-Abl tyrosine kinase inhibitors such as imatinib and
      dasatinib achieve cytogenetic disease remission (ie, Philadelphia chromosome
      positive cells undetectable by cytogenetic evaluation). However, more sensitive
      methods are required for monitoring residual disease (ie, molecular monitoring of
      BCR-ABL transcript levels). It is generally accepted that molecular responses
      have prognostic significance. Patients with CP CML who achieve early molecular
      responses are more likely to achieve durable cytogenetic responses and are less
      likely to experience disease progression. Rising BCR-ABL transcript levels also
      indicate loss of response, often as a consequence of developing BCR-ABL
      mutations. However, some studies have suggested that patients who achieve
      complete cytogenetic disease remission may not derive an additional prognostic
      benefit from achieving a major molecular response. Practical issues also exist
      for molecular monitoring with respect to restricted access and variability in
      methodologies and data reporting. Although molecular monitoring has a clear role
      in assessing residual disease and determining the risk of disease progression in
      patients with CML, the importance of cytogenetic monitoring should not be
      ignored.

PMID- 18348295
TI  - Histologic response of dose-intense chemotherapy with preoperative
      hypofractionated radiotherapy for patients with high-risk soft tissue sarcomas.
AB  - BACKGROUND: The authors studied a dose-intense regimen of epirubicin and
      ifosfamide with hypofractionated preoperative radiotherapy for high-risk soft
      tissue sarcomas. The primary objective was estimation of the rate of >or=95%
      pathologic necrosis. METHODS: Twenty-five patients with intermediate-grade or
      high-grade, localized soft tissue sarcomas of the extremity or body wall
      measuring >5 cm were treated with epirubicin at a dose of 30 mg/m(2)/day on Days
      1 to 4 and ifosfamide at a dose of 2.5 g/m(2)/day on Days 1 to 4 every 21 days
      for 3 preoperative and 3 postoperative cycles. A total of 28 grays of radiation
      was administered over 8 fractions during Cycle 2 of preoperative therapy
      (epirubicin was omitted). RESULTS: Sixteen patients (64%) completed all
      chemotherapy cycles and the average delivered dose intensity relative to intended
      therapy was 69%. Twenty-one patients (84%) experienced grade 4 toxicity (using
      the National Cancer Institute Common Terminology Criteria for Adverse Events
      [version 2.0]), which was predominantly hematologic. Notable toxicities included
      neutropenic fever (40%), ifosfamide-induced encephalopathy (24%), and grade 3/4
      anemia (64%). Postoperative wound complications requiring a surgical procedure
      occurred in 20% of patients. The rate of >or=95% pathologic necrosis was 40% (95%
      confidence interval [95% CI], 21-59%). Estimates of 2-year overall and disease
      free survival were 84% (95% CI, 66-100%) and 62% (95% CI, 37-86%), respectively.
      CONCLUSIONS: A high rate of >or=95% pathologic necrosis was noted with this
      aggressive chemoradiotherapy regimen. The occurrence of significant acute
      toxicities limited the delivery of the intended dose intensity.

PMID- 18348296
TI  - Prognostic factors for high-risk early-stage epithelial ovarian cancer: a
      Gynecologic Oncology Group study.
AB  - BACKGROUND: The purpose was to identify the factors predictive of recurrence and
      survival in patients with high-risk (stage I, grade 3; stage IC, stage II, or
      clear cell) epithelial ovarian cancer after adjuvant therapy. METHODS: Data was
      extracted from patients who underwent primary surgery followed by adjuvant
      therapy in 2 randomized trials by the Gynecologic Oncology Group (Protocols 95
      and 157). Kaplan-Meier survival estimates and Cox proportional hazards model
      adjusted for covariates were used for analyses. RESULTS: Of 506 patients (median
      age = 56.2 years), 347 (68.6%) had stage I and 159 (31.4%) had stage II cancers.
      The 5-year recurrence-free (RFS) and overall survivals (OS) were 75.5% and 81.7%,
      respectively. On multivariate analysis, older age, higher stage, higher grade,
      and malignant cytology were independent prognostic factors predictive for
      recurrence and poorer survival. The risk of recurrence was higher for those >/=60
      versus < 60 years (hazards ratio [HR] = 1.57, 95% confidence interval [CI], 1.12
      2.19), stage II (stage II: HR = 2.70, 95% CI, 1.41-5.16) versus stage IA or IB,
      grade 2 (HR = 1.84, 95% CI, 1.04-3.27) and grade 3 (HR = 2.47, 95% CI, 1.39-4.37)
      versus grade 1, and positive versus negative cytology (HR = 1.72, 95% CI, 1.21
      2.45). By using these factors in a prognostic index, those with low-risk (no or 1
      risk factor), intermediate-risk (2 factors), and high-risk (3-4 risk factors)
      disease had survivals of 88%, 82%, and 75%, respectively (P < .05). CONCLUSIONS:
      Age, stage, grade, and cytology are important prognostic factors in high-risk
      early-stage epithelial ovarian cancer. This information may be used in the design
      of future clinical trials.

PMID- 18348298
TI  - Dual focal adhesion kinase/Pyk2 inhibitor has positive effects on bone tumors:
      implications for bone metastases.
AB  - BACKGROUND: Lytic bone metastases occur frequently in cancer patients and present
      major clinical issues including lack of effective therapies. The mechanism of
      lytic bone metastases involves interactions between tumor cells, bone matrix, and
      bone cells. Both focal adhesion kinase (FAK) and Pyk2 are implicated in the
      biology and physiology of bone and cancer. METHODS: The efficacy of PF-562,271
      was evaluated using MDA-MB-231 cells implanted in the tibia of nude rats. The
      drug was administered orally at a dose of 5 mg/kg, 7 days per week for 28 days.
      Serum and urine biomarkers, imaging, and histologic techniques were deployed to
      monitor tumor take rate, disease progression, and response to therapy. RESULTS:
      The compound was well tolerated. Both compound-treated groups demonstrated
      significant and similar increases in osteocalcin and cancellous bone parameters.
      Radiographic evaluation of tumor-bearing tibiae revealed tumor expansion in
      nontreated rats compared with a decrease in tumor growth and signs of bone
      healing in rats treated with PF-562,271. Tartrate-resistant acid phosphatase and
      fluorescent in situ hybridization analysis revealed that the majority of bone
      resorption at the tumor site was performed by osteoclasts of rat origin.
      CONCLUSIONS: The oral administration of PF-562,271 at a dose of 5 mg/kg
      suppressed the growth and local spread of intratibial tumors and restored tumor
      induced bone loss. The unique ability of PF-562,271 to both curb tumor growth and
      safely increase bone formation may be an effective therapy for many cancer
      patients with bone metastases and cancer-associated osteoporosis.

PMID- 18348297
TI  - Metabolic changes during gonadotropin-releasing hormone agonist therapy for
      prostate cancer: differences from the classic metabolic syndrome.
AB  - BACKGROUND: In men with prostate cancer, gonadotropin-releasing hormone (GnRH)
      agonists increase fat mass, decrease insulin sensitivity, and increase
      triglycerides, features that are shared with metabolic syndrome. To the authors'
      knowledge, however, less is known regarding the effects of GnRH agonists on other
      attributes of the metabolic syndrome. METHODS: In an open-label prospective
      study, 26 men with recurrent or locally advanced prostate cancer were treated
      with leuprolide for 12 months. Outcomes included changes in blood pressure, body
      composition, lipids, adipocytokines, and C-reactive protein. RESULTS: The mean
      weight, body mass index, and waist circumference increased significantly from
      baseline to Month 12 (P < .001 for each comparison). Fat mass increased by 11.2%
      +/- 1.5% (P < .001) and the percentage lean body mass decreased by 3.6% +/- 0.5%
      (P < .001). The total abdominal fat area increased by 16.5% +/- 2.6% (P < .001),
      with the accumulation of subcutaneous fat accounting for 94% of the observed
      increase. The waist-to-hip ratio and blood pressure did not change significantly.
      Serum high-density lipoprotein (HDL) cholesterol concentrations increased
      significantly (P = .002). Serum adiponectin levels increased by 36.4 +/- 5.9%
      from baseline to Month 3 and remained significantly elevated through Month 12 (P
      < .001). Resistin and C-reactive protein levels did not change significantly.
      CONCLUSIONS: The term metabolic syndrome does not appear to adequately describe
      the effects of GnRH agonists in men with prostate cancer. In contrast to the
      metabolic syndrome, GnRH agonists increase subcutaneous fat mass, HDL
      cholesterol, and adiponectin, and do not alter the waist-to-hip ratio, blood
      pressure, or C-reactive protein level.

PMID- 18348299
TI  - Lobular neoplasia on core needle biopsy does not require excision.
AB  - BACKGROUND: Lobular neoplasia (LN), encompassing atypical lobular hyperplasia
      (ALH) and lobular carcinoma in situ (LCIS), is often an incidental finding on
      core needle biopsies (CNBs) performed in instances of radiologic densities and/or
      calcifications. Because LN is generally considered a risk factor for breast
      carcinoma, the utility of subsequent excision is controversial. METHODS: The
      authors' database yielded 98 cases of LCIS and/or ALH. Cases containing LN
      accompanied by a second lesion mandating excision (eg, radial scar, atypical
      ductal hyperplasia [ADH]) and those failing to meet strict diagnostic criteria
      for LN (eg, atypical cells, mitoses, single-cell necrosis) were excluded.
      Radiographic calcifications were correlated with their histologic counterparts in
      terms of size, number, and pattern. RESULTS: Ninety-one biopsies were performed
      for calcifications and 7 were performed for mass lesions. The ages of the
      patients ranged from 35 to 82 years. Fifty-three patients were followed
      radiologically without excision, 42 of whom had available clinicoradiologic
      information. The 45 patients who underwent excision were without disease at
      follow-up periods ranging from 1 to 8 years. Of these 45 patients, 42 (93%) had
      biopsy results demonstrating only LN. The remaining 3 patients had biopsies with
      the following findings: ADH in 1 biopsy, residual LCIS and a separate minute
      focus of infiltrating lobular carcinoma (clearly an incidental finding) in the
      second biopsy, and ductal carcinoma in situ admixed with LCIS in the third biopsy
      (a retrospective examination performed by 2 blinded breast pathologists revealed
      foci of atypical cells and mitoses). CONCLUSIONS: Excision of LN is unnecessary
      provided that: 1) careful radiographic-pathologic correlation is performed; and
      2) strict histologic criteria are adhered to when making the diagnosis. Close
      radiologic and clinical follow-up is adequate.

PMID- 18348300
TI  - Indicators of survival duration in ovarian cancer and implications for
      aggressiveness of care.
AB  - BACKGROUND: Ovarian cancer patients frequently receive chemotherapy near the end
      of life. The purpose of the current study was to develop indicators that
      characterize those ovarian cancer patients who have a short life span. METHODS:
      The medical charts of deceased epithelial ovarian cancer patients were
      retrospectively reviewed from 2000 through 2006. All patients received primary
      debulking surgery and adjuvant chemotherapy. Aggressiveness of cancer care within
      the last month of life was measured by chemotherapy regimens, emergency room
      visits, and hospitalizations. Significant clinical events (SCE) were defined as
      ascites, bowel obstruction, and pleural effusion. Survival quartiles were
      compared using chi-square and Student t test statistics. Multiple regression
      analysis was performed using survival duration as a dependent variable. RESULTS:
      In all, 113 patients with epithelial ovarian cancer were reviewed. Patients had
      increased hospitalizations (P < .001) and SCE (P < .001) as they approached the
      end of life. There was no difference in the pattern of hospitalizations and SCE
      between the top and bottom survival quartiles. Patients with a shorter survival
      time had a trend toward increased chemotherapy during their last 3 months of life
      (P = .057) and had increased overall aggressiveness of care (P = .013). In
      patients with a disease remission, the length of initial remission time was found
      to be significant in predicting survival (P < .01). Time to second disease
      recurrence was also significant in predicting survival time (P < 0.01).
      CONCLUSIONS: Patients who received aggressive care did not have improvement in
      survival. Short disease remissions and increasing hospitalizations with SCE
      should be indicators of the appropriateness of reducing cure-oriented therapies
      and increasing palliative interventions.

PMID- 18348302
TI  - Valproic acid for the treatment of myeloid malignancies.

PMID- 18348303
TI  - Long-term outcome of esophageal mucosal squamous cell carcinoma without
      lymphovascular involvement after endoscopic resection.
AB  - BACKGROUND: Esophageal cancer is an aggressive cancer with a reported 3-year
      survival of 20%. However, early-stage esophageal cancer can be cured by
      endoscopic resection (ER). The long-term survival of esophageal mucosal squamous
      cell carcinoma after ER was investigated by calculating the standard mortality
      rate (SMR). METHODS: From January 1995 to December 2004, 110 patients with 138
      esophageal mucosal squamous cell carcinomas without lymphovascular involvement
      were treated by ER. Long-term survival after ER was compared with that in the
      general population by calculating SMR. Subgroup analysis of patients without
      second primary cancer diagnosed within 1 year before ER (subgroup A) was also
      performed. RESULTS: A total of 108 patients (98.2%) were followed-up completely,
      with a mean observation period of 4.7 (0.4-11.3) years. The cumulative 5-year
      survival rate of all patients and subgroup A was 79.5% and 86.6%, respectively.
      Overall mortality (SMR, 1.68; 95% confidence interval [CI], 1.05-2.55) and
      mortality from malignant tumor (SMR, 3.14; 95% CI, 1.79-5.09) was significantly
      higher than that in the general population. SMR of esophageal cancer was high,
      although it was not significantly different from that in the general population
      (SMR, 4.82; 95% CI, 0.06-26.81). In subgroup A overall mortality (SMR, 0.86; 95%
      CI, 0.41-1.57) was similar to that in the general population. CONCLUSIONS: High
      overall mortality in patients with esophageal mucosal cancer after ER was mainly
      due to elevated mortality from second primary cancer. Favorable mortality in
      subgroup A indicates the efficiency of ER as a curative treatment for esophageal
      mucosal cancer.

PMID- 18348304
TI  - Telomere length and telomerase subunits as diagnostic and prognostic biomarkers
      in Barrett carcinoma.
AB  - BACKGROUND: Maintenance of telomeres has been identified as an essential
      regulator of proliferative capacity and genomic integrity in malignant tumors.
      The authors evaluated telomere length and telomerase subunits, hTR and hTERT, as
      prognostic markers in patients with Barrett carcinoma. METHODS: Telomere length
      was measured by Southern blot analysis and hTR expression and hTERT expression by
      real-time polymerase chain reaction in both cancer tissue and adjacent
      noncancerous Barrett mucosa in resection specimens from 46 patients with Barrett
      carcinoma (International Union Against Cancer [UICC] stages I-III). The median
      follow-up time of the surviving patients was 79 months. RESULTS: Cancer tissue
      expressed more hTERT-mRNA than noncancerous mucosa (P < .05). Telomere lengths in
      cancer tissue and in noncancerous mucosa increased with higher pT category (P =
      .08 and P = .05, respectively). Twenty-one patients who died of tumor recurrence
      showed significantly longer telomeres in cancer tissue compared with 25 patients
      without tumor-related deaths (P < .05). Telomere length in both cancer tissue and
      in noncancerous mucosa and the telomere-length ratio cancer:noncancerous tissue
      were correlated with overall survival. In multivariate analysis, the telomere
      length ratio proved to be an independent prognostic parameter (P < .02; relative
      risk of death 3.4; confidence interval, 1.3-8.9). Ten patients with telomere
      length ratios >1.17 had a significantly poorer overall survival compared with 36
      patients with telomere-length ratios <or=1.17 with 5-year survival rates of 0%
      and 60%, respectively (P < .02). CONCLUSIONS: Telomere length and telomerase
      subunits were identified as diagnostic and prognostic biomarkers for Barrett
      carcinoma. Genetic alterations found in adjacent noncancerous mucosa suggested a
      "field effect" in Barrett carcinoma.

PMID- 18348306
TI  - Significance of HER2 and C-MYC oncogene amplifications in breast cancer in atomic
      bomb survivors: associations with radiation exposure and histologic grade.
AB  - BACKGROUND: It has been postulated that radiation induces breast cancers in
      atomic bomb (A-bomb) survivors. Oncogene amplification is an important mechanism
      during breast carcinogenesis and also serves as an indicator of genomic
      instability (GIN). The objective of this study was to clarify the association of
      oncogene amplification in breast cancer in A-bomb survivors with radiation
      exposure. METHODS: In total, 593 breast cancers were identified in A-bomb
      survivors from 1968 to 1999, and the association between breast cancer incidence
      and A-bomb radiation exposure was evaluated. Invasive ductal cancers from 67
      survivors and 30 nonsurvivors were analyzed for amplification of the HER2 and C
      MYC genes by fluorescence in situ hybridization, and expression levels of hormone
      receptors were analyzed by immunostaining. RESULTS: The incidence rate increased
      significantly as exposure distance decreased from the hypocenter (hazard ratio
      per 1-km decrement, 1.47; 95% confidence interval [95% CI], 1.30-1.66). The
      incidence of HER2 and C-MYC amplification was increased significantly in the
      order of the control group, the distal group (P = .0238), and the proximal group
      (P = .0128). Multivariate analyses revealed that distance was a risk factor for
      the coamplification of C-MYC and HER2 in breast cancer in survivors (odds ratio
      per 1-km increment, 0.17; 95% CI, 0.01-0.63). The histologic grade of breast
      cancers became significantly higher in the order of the control group, the distal
      group, and the proximal group and was associated with oncogene amplifications.
      CONCLUSIONS: The current results suggested that A-bomb radiation may affect the
      development of oncogene amplification by inducing GIN and may be associated with
      a higher histologic grade in breast cancer among A-bomb survivors.

PMID- 18348307
TI  - Survival and predictors of outcome in patients with acute leukemia admitted to
      the intensive care unit.
AB  - BACKGROUND: Predictors of outcome and rates of successful discharge have not been
      defined for patients with acute leukemia admitted to intensive care units (ICUs)
      in the US. METHODS: This is a retrospective analysis of 90 patients with acute
      leukemia (no history of bone marrow transplant) admitted to an ICU from 2001
      2004. The primary endpoints were improvement and subsequent discharge from the
      ICU, discharge from the hospital, and 2-month survival after hospital discharge.
      Secondary endpoints were 6- and 12-month survival. Univariate and multivariate
      logistic regression analyses were performed to identify factors predicting
      outcome. RESULTS: The median age of patients was 54 years and 48 (53%) were male.
      The most common reason for ICU transfer for all patients was respiratory
      compromise. The majority of all patients (68%) were eventually placed on
      ventilator support and approximately half required pressors. During the ICU
      course, 29 patients (32%) improved and subsequently resumed aggressive leukemia
      management, and 24 patients (27%) survived to be discharged from the hospital.
      The 2-, 6-, and 12-month overall survival was 24 (27%), 16 (18%), and 14 (16%),
      respectively. Higher APACHE II score, use of pressors, undergoing bone marrow
      transplantation preparative regimen, and adverse cytogenetics predicted worse
      outcome. Newly diagnosed leukemia, type of leukemia, or age did not. CONCLUSIONS:
      One of 4 patients with acute leukemia survived an ICU admission to be discharged
      from the hospital and were alive 2 months later. A diagnosis of acute leukemia
      should not disqualify patients from an ICU admission.

PMID- 18348308
TI  - Surgical staging and cervical cancer: after 30 years, have we reached a
      conclusion?

PMID- 18348309
TI  - Acute phase phospholipids related to the cardiolipin of mitochondria in the sera
      of patients with chronic fatigue syndrome (CFS), chronic Ciguatera fish poisoning
      (CCFP), and other diseases attributed to chemicals, Gulf War, and marine toxins.
AB  - This study examined 328 CFS sera in a study with 17 CCFP, 8 Gulf War Veterans
      (GWV), 24 Prostate Cancer (PC), and 52 normal sera in the modified Membrane
      Immunobead Assay (MIA) procedure for CTX. Three hundred and twenty-eight CFS
      patients' sera were examined by the modified MIA with purified MAb-CTX and 91.2%
      gave a titre > or =1:40. 76% of the 17 CCFP sera samples and 100% of the 8 GWV
      sera samples also had a titre > or =1:40. 92.3% of 52 normal sera showed titres
      of 1:20 or less, while 4 gave titres of > or =1:40. In addition, 41 sera were
      examined for Anti-Cardiolipin (aCL) by a commercial ELISA procedure with 87.8%
      demonstrating IgM, IgM+IgA, or IgM+IgG aCL antibodies. These results showed
      mostly the IgM aCL antibody alone in the sera samples. In addition, 41 serum
      samples were examined for aCL, with 37 showing positive for aCL, representing
      90.2% positive for the three disease categories examined: CFS, CCFP and GWV.
      Examination for antiMitochondrial-M2 autoantibody (aM-M2) in 28 patients (CFS
      (18), CCFP (5), and GWV (5)) was negative for aM-M2. Inhibition analysis with
      antigens, CTX, CFS "Acute Phase Lipids", commercial Cardiolipin (CL) and 1,2
      Dipalmitoyl-sn-Glycero-3-[Phospho-L-Serine] (PS) and antibodies, MAb-CTX and aCL
      from patients' serum show that the phospholipids in CL and CTX are antigenically
      indistinguishable with antibodies MAb-CTX and CFS-aCL. Preliminary chemical
      analyses have shown the lipids to be phospholipids associated with CL of the
      mitochondria. We designate this "Acute Phase Lipid" comparable to "Acute Phase
      Proteins" (C-reactive protein (CRP) and Serum Amyloid A (SAA)) in inflammatory
      conditions.

PMID- 18348310
TI  - Does cigarette smoking affect the diagnostic reliability of hemoglobin alpha 2
      delta 2 (HbA2)?
AB  - Quantitation of hemoglobin alpha 2 delta 2 (HbA2) is a basic and confirmatory
      test in diagnosing the carrier state of beta-thalassemia. The present study was
      designed to investigate the effect of cigarette smoking on the diagnostic
      reliability of HbA2. A total of 2,867 (654 smokers and 2,213 never smokers) male
      subjects were involved in the present study. The subjects were categorized into
      three groups according to their laboratory findings: beta-thalassemia minor, iron
      deficient, and normal groups. Complete blood count (CBC) parameters and HbA2
      levels were compared between smokers and never smokers of each group according to
      the independent-samples t-test using the SPSS program, significance results were
      reported at P<0.05. The results showed a significant increase in red blood cell
      (RBC) mass (RBC count and hematocrit [Hct]) and Hb concentration in smokers of
      all groups; however, no significant differences were reported in the HbA2 level
      between smokers and never smokers in all groups. It was concluded that cigarette
      smoking does not affect the diagnostic reliability of the HbA2 test.

PMID- 18348311
TI  - Preliminary clinical measurement of the expression of TNF-related apoptosis
      inducing ligand in patients with ankylosing spondylitis.
AB  - It has recently been reported that tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL) plays various roles in such autoimmune diseases as
      diabetes, multiple sclerosis (MS), and systemic lupus erythematosus (SLE).
      However, it has still remained unclear whether there is a close relationship
      between TRAIL and ankylosing spondylitis (AS). In this study, we investigated the
      association between the expression of TRAIL and AS. The specific messenger
      ribonucleic acid (mRNA) levels of TRAIL in peripheral blood mononuclear cells
      (PBMCs), serum sTRAIL, and TNF-alpha concentrations from 60 AS patients, 20
      rheumatoid arthritis (RA) patients, and 30 healthy controls were determined by
      real-time fluorescent quantitative polymerase chain reaction (PCR) and enzyme
      linked immunosorbent assay (ELISA). The results indicated that the expression
      levels of TRAIL mRNA, and serum sTRAIL were significantly elevated in AS
      patients, compared with RA patients and healthy controls, and there was a close
      association between TRAIL mRNA and sTRAIL levels. However, there was no
      significant difference between human leukocyte antigen (HLA)-B27-positive and 
      negative AS patients. In HLA-B27-positive patients, TRAIL mRNA and sTRAIL closely
      correlated with serum TNF-alpha and C-reactive protein (CRP), but did not
      correlate in HLA-B27-negative patients. In conclusion, upregulated expression of
      TRAIL might be somewhat specific for evaluation of AS.

PMID- 18348312
TI  - Gamma heavy chain disease in a patient with diabetes and chronic renal
      insufficiency: diagnostic assessment of the heavy chain fragment.
AB  - Heavy chain diseases are rare B-cell disorders that are characterized by an
      overproduction of abnormal and structurally incomplete monoclonal immunoglobulin
      (Ig) heavy chains and are devoid of light chains. We describe a case of a 62 year
      old African-American woman with a long history of poorly controlled type 2
      diabetes and subsequent probable diabetic nephropathy, hypertension, and recent
      onset of peripheral neuropathy involving all extremities. Routine laboratory
      testing revealed a distinct beta spike by urine protein electrophoresis (UPEP).
      No serum abnormality was noted on serum protein electrophoresis (SPEP). Serum and
      urine immunofixation demonstrated an IgG heavy chain protein devoid of any
      corresponding light chains. IgG subclasses identified IgG1 as the predominant IgG
      component but when we added all the subclasses, the sum, 683.4 mg/dL, failed to
      come close to our total IgG of 1,770 mg/dL. Therefore, a urine IgG subclass
      determination was performed in-house and we identified a subclass 3 gamma chain.
      In conclusion, we portray a patient with an underlying monoclonal gamma heavy
      chain disease (HCD) who presented with a complex medical history. The evaluation
      of IgG subclasses in the context of a HCD may be limited by the capability of the
      test to recognize the particular IgG fragment.

PMID- 18348314
TI  - Cellular immune response from Chagasic patients to CRA or FRA recombinant
      antigens of Trypanosoma cruzi.
AB  - We propose to analyze the relation between the cellular immune response of
      Chagas' disease patients after in vitro stimulation of peripheral blood
      mononuclear cells (PBMC) with recombinant antigens cytoplasmatic repetitive
      antigen (CRA) or flagellar repetitive antigen (FRA) of T. cruzi and the chronic
      clinical forms of disease. Cells were stimulated using phytohemagglutinin, CRA,
      FRA, or a soluble antigen of Epimastigota (Ag-Epi) for 24 hr, 72 hr, or 6 days.
      The proliferation of cells was evaluated after 6 days of culture by
      quantification of incorporated 3H-thymidine. Cytokines were measured in the
      supernatants obtained after 24 hr (tumor necrosis factor [TNF]-alpha and
      interleukin [IL]-4), 72 hr (IL-10), and 6 days (interferon [IFN]-gamma) using
      enzyme-linked immunosorbent assay (ELISA). Cells of the Chagas patients
      stimulated with the recombinant antigens exhibited higher proliferation responses
      compared with that of non-Chagas (NC) individuals. However, when proliferation
      was compared between patients with the cardiac form (CF) or indeterminate form
      (IF), it was not possible to establish a difference in the response. So far as
      the cytokines secreted in the culture supernatants after stimulation in vitro
      with T. cruzi antigens were concerned, the results showed that CRA, as well as
      Epi-Ag, were able to stimulate the production of TNF-alpha and IFN-gamma in
      Chagas patients as compared with NC individuals. However, the cytokine levels
      after stimulation with the T. cruzi antigens were not different between the
      patients with CF and IF. CRA was capable of inducing a T helper type 1 (Th1)
      immune response, with elevated production of TNF-alpha and IFN-gamma in Chagas
      patients that are carriers of CF and IF clinical forms.

PMID- 18348315
TI  - An optimized nested polymerase chain reaction (PCR) approach allows detection and
      characterization of human immunodeficiency virus type 1 (HIV-1) env and gag genes
      from clinical samples.
AB  - The needs for development and/or improvement of molecular approaches for
      microorganism detection and characterization such as polymerase chain reaction
      (PCR) are of high interest due their sensitivity and specificity when compared to
      traditional microbiological techniques. Considering the worldwide importance of
      human immunodeficiency virus type 1 (HIV-1) infection, it is essential that such
      approaches consider the genetic variability of the virus, the heterogeneous
      nature of the clinical samples, the existence of contaminants and inhibitors, and
      the consequent needs for standardization in order to guarantee the
      reproducibility of the methods. In this work we describe a nested PCR assay
      targeting HIV-1 virus gag and env genes, allowing specific and sensitive
      diagnosis and further direct characterization of clinical samples. The method
      described herein was tested on clinical samples and allowed the detection of HIV
      1 presence in all samples tested for the gag gene and 90.9% for the env gene,
      revealing sensitivities of 1 fg and 100 fg, respectively. Also, no cross
      reactions were observed with DNA from infected and noninfected patients and the
      method allowed detection of the env and gag genes on an excess of 10(8) and 10(4)
      of human deoxyribonucleic acid (DNA), respectively. Furthermore, it was possible
      to direct sequence all amplified products, which allowed the sub typing of the
      virus in clinical samples.

PMID- 18348316
TI  - Prediction of diagnosis of immunoglobulin A nephropathy prior to renal biopsy and
      correlation with urinary sediment findings and prognostic grading.
AB  - Several clinical markers correlate well with the diagnosis and prognosis of IgA
      nephropathy (IgAN). In the present study, we re-evaluated the usefulness of these
      four clinical markers for prediction of the diagnosis of patients with IgAN
      through a comparison between many more patients with IgAN and those with other
      types of renal diseases. 364 patients with IgAN and 289 with other types of renal
      disease were examined. An analysis was performed prior to renal biopsy, using
      clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood
      cells in urinary sediments, and urinary protein. Patients with IgAN were divided
      into four groups according to histopathological findings. Presence of microscopic
      hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3
      ratios are useful for prediction of diagnosis of IgAN and distinguishing it from
      other renal diseases. Blood pressure, urinary protein, serum uric acid, renal
      function, and urinary sediment findings may be useful for prediction of
      prognostic grading in patients with IgAN.

PMID- 18348317
TI  - Fast detection of MYCN copy number alterations in brain neuronal tumors by real
      time PCR.
AB  - Increased MYCN gene copy number is a characteristic property of neurogenic
      tumors. Fluorescence in situ hybridization (FISH) and array-based comparative
      genomic hybridization (array-CGH) are traditionally used to determine MYCN
      amplification for tumor stratification. A unique ability of real-time
      quantitative polymerase chain reaction (qPCR) to determine gene copy number, even
      within a small percent of observed tumor cells, and can be more appropriate. MYCN
      genomic copy number from 44 human brain tumors (22 medulloblastomas and 22
      neurocytomas) was determined by means of FISH, array-CGH, and qPCR. By qPCR, with
      the original set of oligonucleotides, 17 out of 44 (38.6%) tumors were found to
      contain a 1.3- to 2.9-fold increase of MYCN defined as low-level gain. An
      absolute qPCR method was used to get high accuracy of results. Strong correlation
      was observed between the three methods: for medulloblastomas, r=1 (P<0.01)
      between FISH and array-CGH and r=0.92 (P<0.01) between qPCR and FISH/array-CGH.
      For neurocytomas, r=0.9 (P<0.01) between FISH and array-CGH and r=0.34/0.43
      (P<0.01) between qPCR and FISH/array-CGH. Absolute qPCR assays possess high
      precision compared to other conventional methods and can be used for accurate and
      quickness detection of MYCN status (low-level gene gain and amplification).

PMID- 18348318
TI  - Detection and significance of serum protein markers of small-cell lung cancer.
AB  - Currently, no satisfactory biomarkers are available to screen for small-cell lung
      cancer (SCLC). We applied a surface-enhanced laser desorption/ionization time-of
      flight mass spectrometry (SELDI-TOF MS) ProteinChip system to detect 150 serum
      samples (including 54 SCLC patients, 24 non-small cell lung cancer [NSCLC]
      patients, 32 pneumonia patients, and 40 healthy individuals). The spectra data
      were analyzed by support vector machine (SVM) and potential biomarkers were
      chosen for the system training and used to construct diagnostic model. Pattern 1,
      constructed of four protein peaks with mass/charge (m/z) of 4,293 Da, 4,612 Da,
      6,455 Da, and 7,582 Da, separated SCLC patients from the healthy individuals with
      a sensitivity of 88.9% and a specificity of 85.7%. This pattern performed
      significantly better than the current marker, neuron-specific enolase (NSE)
      (P<0.05). Pattern 2, constructed of protein peaks with mass/charge (m/z) of 2,764
      Da and 1,7368 Da, separated SCLC from pneumonia with a sensitivity of 88.9% and a
      specificity of 91.7%. Pattern 3, constructed of another three protein peaks with
      m/z of 3,912 Da, 7,562 Da, and 13,777 Da, separated SCLC from NSCLC. The
      sensitivity and specificity were 83.3% and 75.0%, respectively. These results
      suggested that SELDI-TOF MS combined with support vector machine yields
      significantly higher sensitivity and specificity for the detection of serum
      protein of SCLC.

PMID- 18348319
TI  - Systematic characterization of the murine mitochondrial proteome using
      functionally validated cardiac mitochondria.
AB  - Mitochondria play essential roles in cardiac pathophysiology and the murine model
      has been extensively used to investigate cardiovascular diseases. In the present
      study, we characterized murine cardiac mitochondria using an LC/MS/MS approach.
      We extracted and purified cardiac mitochondria; validated their functionality to
      ensure the final preparation contains necessary components to sustain their
      normal function; and subjected these validated organelles to LC/MS/MS-based
      protein identification. A total of 940 distinct proteins were identified from
      murine cardiac mitochondria, among which, 480 proteins were not previously
      identified by major proteomic profiling studies. The 940 proteins consist of
      functional clusters known to support oxidative phosphorylation, metabolism, and
      biogenesis. In addition, there are several other clusters, including proteolysis,
      protein folding, and reduction/oxidation signaling, which ostensibly represent
      previously under-appreciated tasks of cardiac mitochondria. Moreover, many
      identified proteins were found to occupy other subcellular locations, including
      cytoplasm, ER, and golgi, in addition to their presence in the mitochondria.
      These results provide a comprehensive picture of the murine cardiac mitochondrial
      proteome and underscore tissue- and species-specification. Moreover, the use of
      functionally intact mitochondria insures that the proteomic observations in this
      organelle are relevant to its normal biology and facilitates decoding the
      interplay between mitochondria and other organelles.

PMID- 18348322
TI  - Utility of separation science in metabolomic studies.
AB  - Metabolomics, or alternately metabonomics, an emerging field of biochemical
      research, is a complementary technique to genomics, transcriptomics, and
      proteomics. Direct quantitative measurements of metabolite expressions in urine,
      serum, plasma, and tissue are essential for the study of biological processes in
      normal and disease states. Since the number of metabolites in a biological sample
      is large separation science plays an important role in metabolomic research. This
      review describes the role of GC, HPLC, CE, and supercritical fluid chromatography
      in metabolomic research. The application of each technique is discussed and its
      advantages and limitations are discussed with selective illustrative examples.

PMID- 18348323
TI  - Micellar electrokinetic chromatography.

PMID- 18348324
TI  - Electrokinetic chromatography with polymeric pseudostationary phases.
AB  - Recent research and development efforts concerning polymeric pseudostationary
      phases (PSPs) for electrokinetic chromatography are reviewed. The introduction of
      new materials, characterization of structural effects on performance and
      selectivity, applications, and the use of polymeric PSPs with mass spectrometric
      detection are considered. Very interesting results concerning the effects of
      polymer structure have been reported. Significant developments have also been
      reported in the development of novel applications of polymeric PSPs, particularly
      for sample preconcentration using micellar affinity gradient focusing. The use of
      mass spectrometric detection with electrokinetic chromatography has seen
      significant development, and recent reports indicate that this is a robust and
      sensitive approach.

PMID- 18348325
TI  - Combinatorial transition-metal catalysis: mixing monodentate ligands to control
      enantio-, diastereo-, and regioselectivity.
AB  - This review focuses on a new approach to combinatorial homogeneous transition
      metal catalysis which goes beyond the traditional parallel preparation of modular
      ligands. It is based on the use of mixtures of monodentate ligands L(a) and L(b),
      which upon exposure to a transition metal (M) form not only the two
      homocombinations [ML(a)L(a)] and [ML(b)L(b)], but also the heterocombination
      [ML(a)L(b)]. If the latter is more reactive and selective than the
      homocombinations, an improved catalyst system is formed without the need to
      synthesize new ligands. Thus, the control of enantio,- diastereo-, and
      regioselectivity is possible.

PMID- 18348328
TI  - Comparison of partial filling MEKC analyses of steroids with use of ESI-MS and UV
      spectrophotometry.
AB  - Until now, partial filling micellar EKC-ESI-MS (PF-MEKC-ESI-MS) has seldom been
      applied for human biomolecules. In this study, determination of three
      electrically neutral endogenous steroid hormones, namely androstenedione,
      testosterone, and epitestosterone, by PF-MEKC-ESI-MS was investigated. Since ESI
      MS and ESI-MS/MS behaviors of testosterone and epitestosterone proved to be
      nearly identical, efficient separation of the two compounds was required to
      obtain reliable identification. The chemical conditions as well as the
      instrumental parameters affecting the PF-MEKC-ESI-MS analysis were researched. In
      optimal conditions, ESI-MS showed excellent selectivity, and all the steroids
      could be identified using SIM. LODs were 0.75-5 microg/mL. The results obtained
      by PF-MEKC-ESI-MS were compared with those obtained by corresponding PF-MEKC-UV.
      PF-MEKC-UV provided better resolution, repeatability, and more than ten-fold
      higher sensitivity, in terms of LODs, than PF-MEKC-ESI-MS. The reasons for this
      were carefully examined. In comparison with PF-MEKC-UV, PF-MEKC-ESI-MS suffered
      from greater band broadening owing to the sheath-liquid interface. Resolution was
      also decreased owing to the elevated capillary temperature. Finally, we
      discovered that in the analysis of electrically neutral compounds, in-capillary
      sample concentration by micellar sweeping could be more efficiently utilized in
      PF-MEKC-UV than in PF-MEKC-ESI-MS.

PMID- 18348329
TI  - Determination of triptonide by cloud point extraction combined with MEKC.
AB  - A method has been developed for the determination of triptonide in the
      traditional Chinese herb Tripterygium wilfordii Hook F. by micellar
      electrokinetic capillary chromatography combined with cloud point extraction. The
      analyte was extracted at pH 3.0 by micelles of the nonionic surfactant
      polyoxyethylene 7,5-octylphenyl ether (Triton X-114). A 250-muL aliquot from the
      extracted surfactant-rich phase was diluted to 400 muL with ethanol to reduce its
      viscosity before separation by MEKC. Under optimum conditions, an enrichment
      factor of 25 is obtained and the determination limit of triptonide is found to be
      3.15 x 10(-7) mol/L. The proposed method has been successfully applied to the
      determination of triptonide in T. wilfordii tablet and spiked urine matrix,
      demonstrating the feasibility and reliability of the proposed method.

PMID- 18348332
TI  - Expansion of mesenchymal stem cells using a microcarrier-based cultivation
      system: growth and metabolism.
AB  - For the continuous and fast expansion of mesenchymal stem cells (MSCs),
      microcarriers have gained increasing interest. The aim of this study was to
      evaluate the growth and metabolism profiles of MSCs, expanded in a microcarrier
      based cultivation system. We investigated various cultivation conditions to
      expand goat mesenchymal stem cells on Cytodex 1 microcarriers. These conditions
      differed in feeding regime, i.e. the addition of fresh proliferation medium, with
      or without new microcarriers. For all conditions, cell attachment, cell
      proliferation, energy source consumption, metabolite production, and cell
      distribution on the microcarriers were studied. Attachment efficiencies of 40%
      were obtained followed by successful expansion up to 15 cultivation days.
      Depending on the feeding regime, an exponential growth, stationary growth, and
      decline growth phase could be distinguished. Addition of 30% fresh medium
      containing microcarriers every three days showed the longest continuous
      proliferation of goat MSCs on microcarriers. This feeding regime has the
      advantage that metabolites, such as ammonia, are diluted and that new energy
      sources, such as glucose and glutamine, and additional surface area are provided
      to the cells. In addition, by adding extra microcarriers a more homogenous cell
      distribution on the microcarriers is obtained as a result of bead-to-bead
      transfer. A correlation between nutrient consumption, metabolite production and
      cell growth was observed. The decreasing yield of lactate from glucose over time
      indicated a possible shift in cellular metabolism.

PMID- 18348333
TI  - An optimal method of DNA silver staining in polyacrylamide gels.
AB  - DNA silver staining has widely been used to detect DNA fragments in
      polyacrylamide gels with high sensitivity. We developed an optimal method for DNA
      silver staining on polyacrylamide gels. The novel procedure can be completed
      within 10 min instead of over 20 min with the conventional methods. The
      sensitivity is significantly improved by the silver-ion sensitizer (Eriochrome
      black T (EBT)) and the minimum of 0.11 and 1.75 ng of DNA amount can be detected
      in denaturing and nondenaturing polyacrylamide gel, respectively. Compared with
      the conventional silver staining methods, the improved optimal method can save
      time and display high sensitivity, color uniformity, and long storage time of the
      staining gels.

PMID- 18348334
TI  - Superiority of a new gradient system utilizing a critical threshold for the
      adsorption capacity of polypeptides to column packing when compared with a
      standard gradient system for the simultaneous and quantitative analysis of
      polypeptides.
AB  - Compared with a standard gradient system, the new gradient system which we
      developed has a major advantage because it permits a wide range of acetonitrile
      content, e.g. more than the critical threshold, in the polypeptide solution and
      allows the quantitative analysis of the polypeptide with satisfactory analytical
      precision. Additionally, this new gradient system allows the enhancement of the
      sensitivity of the polypeptide analysis proportionate to the increased volume of
      solution loaded with the same levels of precision. In contrast, when using a
      standard gradient system it is difficult to analyze a polypeptide quantitatively
      with good precision due to either adsorption to various materials or to irregular
      change in the ratio between a retained and a passed peak of the polypeptide.
      Additionally, the appearance of a passed peak results in a loss in the
      sensitivity of the polypeptide analysis, although no adsorption of a polypeptide
      to various materials occurs in a solution with acetonitrile content more than the
      critical threshold. Consequently, the new gradient system is effective for the
      simultaneous and quantitative analysis of different polypeptides with good
      precision and without any loss of sensitivity due to either adsorption to various
      materials or the appearance of a passed peak.

PMID- 18348335
TI  - Determination of plasma topiramate concentration using LC-MS/MS for
      pharmacokinetic and bioequivalence studies in healthy Korean volunteers.
AB  - A rapid, simple and validated liquid chromatography coupled to tandem mass
      spectrometric method (LC-MS/MS) for topiramate analysis in human plasma has been
      applied to pharmacokinetic and bioequivalence studies in 24 healthy male Korean
      volunteers. The procedure involves a simple liquid extraction of topiramate and
      prednisone (internal standard) with acetonitrile and separation by HPLC equipped
      with a Capcell Pak C18 column using acetonitrile-0.1% triethylamine (80:20, v/v)
      as a mobile phase. Detection was carried out on an API 2000 MS system by multiple
      reactions monitoring mode. The ionization was optimized using ESI(-) and
      selectivity was achieved by MS/MS analysis, m/z 338.0 --> 77.5 and m/z 357.1 -->
      327.2 for topiramate and prednisone, respectively. The method had a total run
      time of 2.5 min and showed good linearity over a working range of 20-5000 ng/mL
      in human plasma with a lower limit of quantification of 20 ng/mL. No metabolic
      compounds were found to interfere with the analysis. The inter-day and intra-day
      accuracy were in the ranges of 99.24-116.63 and 93.45-108.68%, respectively, and
      inter-day and intra-day precisions were below 6.24 and 5.25%, respectively. This
      method was successfully applied for pharmacokinetic and bioequivalence studies by
      analysis of blood samples taken up to 96 h after an oral administration of 100 mg
      of topiramate in 24 healthy Korean volunteers.

PMID- 18348336
TI  - HPLC-fluorescence assay for acyclovir in children.
AB  - A simple, accurate, reliable and sensitive HPLC method was developed and
      validated for quantitating acyclovir in human plasma. Sample (100 microL)
      preparation involved addition of guanosine (internal standard) and protein
      precipitation with 7% perchloric acid and centrifugation. Supernatant (20 microL)
      was injected onto a C18 HPLC column with a mobile phase of 0.05 m sodium
      phosphate buffer-acetonitrile (pH 2.35, 992:8, v/v) with 25 microL of 0.4 m
      tetrabutylammonium hydroxide titrant and fluorescence detection (excitation, 260
      nm; emission, 375 nm). Analyte recovery was 101% and the assay response was
      linear over the acyclovir concentration range of 0.1-20 mg/L. Intra- and inter
      day accuracy and precision were less than 7%. The limit of detection and limit of
      quantitation were 0.033 and 0.1 mg/L, respectively. In five paediatric oncology
      patients administered intravenous acyclovir, concentrations ranged from 0.24 to
      43.65 mg/L. This method can be used to measure acyclovir concentrations in
      paediatric patients.

PMID- 18348337
TI  - Rapid screening of polysaccharide-based plasma volume expanders dextran and
      hydroxyethyl starch in human urine by liquid chromatography-tandem mass
      spectrometry.
AB  - The increasing number of samples and target substances in doping control requires
      continuously improved screening methods, combining high-throughput analysis,
      simplified sample preparation, robustness and reliability. Hence, a rapid
      screening procedure based on liquid chromatography-electrospray ionization-tandem
      mass spectrometry with in-source collision-induced dissociation was developed.
      The detection of the polysaccharide-based plasma volume expanders dextran and
      hydroxyethyl starch (HES) in human urine was established without further sample
      preparation. The in-source fragmentation strategy of the approach represented a
      valuable tool in the analysis of the polysaccharide-based compounds, allowing the
      use of tandem mass spectrometry. After direct injection of urine specimens,
      analytes were chromatographically separated on a monolithic reverse-phase column
      and detected via multiple reaction monitoring of diagnostic ions at detection
      limits of 10 microg/mL for HES and 30 microg/mL for dextran. Validation was
      performed regarding the parameters specificity, linearity, precision (8-18%) and
      accuracy (77-105%) and the method was applied to the investigation of
      approximately 400 doping control samples and seven dextran and two hydroxyethyl
      starch post-administration samples. The approach demonstrated its capability as a
      rapid screening tool for the detection of dextran and hydroxyethyl starch and
      represents an alternative to existing screening procedures since time consuming
      hydrolysis or derivatization steps were omitted.

PMID- 18348338
TI  - Determination of oxatomide in human plasma by high-performance liquid
      chromatography-electrospray ionization mass spectrometry.
AB  - A rapid, sensitive and specific high-performance liquid chromatography
      electrospray ionization mass spectrometry (LC-ESI-MS) method has been developed
      and validated for the determination of oxatomide in human plasma. Flunarizine
      hydrochloride was employed as the internal standard (IS). The analytes were
      chromatographically separated on a Shimadzu Shim-pack VP-ODS C18 column (250 x
      2.0 mm i.d.) with a mobile phase consisting of methanol and aqueous ammonium
      acetate solution (10 mm, pH 4.0; 85:15, v/v). Detection was performed on a single
      quadrupole mass spectrometer using an electrospray ionization interface with the
      selected-ion monitoring (SIM) mode. The method showed excellent linearity (r =
      0.9995) over the concentration range of 0.5-500 ng/mL with good accuracy and
      precision. The intra- and inter-batch precisions were within 10% relative
      standard deviation. The recoveries were more than 90%. The validated method was
      successfully applied to a preliminary pharmacokinetic study of oxatomide in
      Chinese healthy male volunteers.

PMID- 18348339
TI  - Simultaneous determination of geniposide and its metabolites genipin and
      genipinine in culture of Aspergillus niger by HPLC.
AB  - When cultivated with Aspergillus niger, geniposide, an important drug, is
      transformed into genipin and genipinine. A simple and rapid HPLC method for
      simultaneous determination of geniposide and its two metabolites in broth of A.
      niger is described. The chromatographic separation was achieved on a C18 ODS
      column (250 x 4.6 mm) by gradient elution with 0.1% formic acid in water and 0.1%
      formic acid in acetonitrile as the gradient mixtures. The flow rate was 1 mL/min,
      the detection wavelength was 238 nm and the column temperature was kept at 28
      degrees C. The retention times of geniposide, genipin and genipinine were 10.9,
      13.8 and 21.5 min, respectively. The mean absolute recoveries of three analysts
      were over 98%. Quantification limits were 0.01 microg/mL for geniposide and 0.02
      microg/mL for the two metabolites. The method was applied for the quantification
      of geniposide, genipin and genipinine during fermentation and the evaluation of
      the bioavailabilities of these three compounds in Caco-2 monolayer.

PMID- 18348340
TI  - Liquid chromatography-electrospray tandem mass spectrometric assay suitable for
      quantitation of YM155, a novel small-molecule survivin suppressant, in dog
      plasma.
AB  - This paper describes a sensitive and selective liquid chromatography with tandem
      mass spectrometry (LC-MS/MS) method for determination of the novel survivin
      suppressant YM155, 1-(2-methoxyethyl)-2-methyl-4,9-dioxo-3-(pyrazin-2-ylmethyl)
      4,9-dihydro-1H-naphtho[2,3-d]imidazolium, which is developed for the treatment of
      solid tumors. This method uses a liquid-liquid extraction from 0.25 mL of dog
      plasma. LC separation was carried out on a Genesis Silica column (50 mm x 3.0 mm
      i.d.) at a flow-rate of 0.5 mL/min. Compounds were eluted using a mobile phase of
      5 mm ammonium acetate and 0.1% formic acid in water-0.1% formic acid in
      acetonitrile, 17:83 (v/v). MS/MS detection was carried out with an MDS-Sciex
      API3000 triple quadrupole mass spectrometer in positive electrospray ionization
      mode. The standard curve was linear from 0.05 to 50 ng/mL (r > or = 0.9968). The
      lower limit of quantitation was 0.05 ng/mL. Good intra- and inter-day assay
      precision (within 7.4% RSD) and accuracy (within +/-12.3%) were obtained. The
      extraction recovery was 66.2%. The method was successfully applied to preclinical
      pharmacokinetic studies in dogs.

PMID- 18348341
TI  - A disposition kinetic study of tramadol in rat perfused liver.
AB  - A recirculated perfusion system was used to investigate the metabolism of
      tramadol, an analgesic agent, in the isolated perfused rat liver. Tramadol was
      added to the perfusion medium at a concentration of 300 ng/ml, and the perfusate
      samples were collected for 180 min. The concentration of tramadol and its three
      main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) and N,O
      didesmethyltramadol (M5) were determined in perfusate samples by a rapid HPLC
      method. All through the study, the phase I metabolism of tramadol led to the
      formation of M1 metabolite from early sampling points while M5 metabolite was
      detectable after 50 min in 6 out of 10 perfused livers and the M2 metabolite was
      not detectable in any experiment. The kinetic parameters of tramadol and two
      detectable metabolites (M1 and M5) were then calculated in perfusate samples. The
      tramadol concentration decreased from 297.8 to 159.6 ng/ml, with a mean half-life
      of 232.4 min and a hepatic clearance of 0.73 ml/min. After 180 min, the mean
      concentration of M1 reached 59.5 ng/ml, resulting in a metabolic ratio of 16%,
      while the formation of M5 metabolite continued to a mean concentration of 14.6
      ng/ml resulting in a metabolic ratio of 2% using AUC((0-180min)).

PMID- 18348342
TI  - CASTLE study showed similar efficacy.

PMID- 18348343
TI  - Abacavir and didanosine increase the risk of heart attack.

PMID- 18348344
TI  - 48-week data released for etravirine (TMC125).

PMID- 18348345
TI  - Isentress maintains reductions in viral load through 48 weeks.

PMID- 18348346
TI  - NYC adults at risk for HIV transmission think they are not.

PMID- 18348347
TI  - Decreased AIDS-related deaths help lower NYC death rate in 2006.

PMID- 18348348
TI  - The US presidential hopefuls' health policies.

PMID- 18348349
TI  - Breaking the silence.

PMID- 18348350
TI  - Paediatric ethics: a repudiation of the Groningen protocol.

PMID- 18348351
TI  - Accuracy of US cancer surveillance under threat.

PMID- 18348352
TI  - Immigrant cancer care: exercises in cost shifting.

PMID- 18348353
TI  - Current awareness in prenatal diagnosis.

PMID- 18348354
TI  - An inhibitor of O-glycosylation induces apoptosis in NIH3T3 cells and developing
      mouse embryonic mandibular tissues.

PMID- 18348355
TI  - [Beta-blockers. Results of utilization in various areas of medicine.
      Pharmacotherapy symposium held at Sava Center 11 July 1992 organized by the
      Pharmacotherapy Section of the Serbian Medical Society].

PMID- 18348356
TI  - The economics of "pay-or-play" mandates.

PMID- 18348357
TI  - Comparing the U.S. and Canadian health care systems.

PMID- 18348358
TI  - The lifetime costs and benefits of medical technology.

PMID- 18348359
TI  - Conditioning factors for fertility decline in Bengal: history, language identity,
      and openness to innovations.

PMID- 18348360
TI  - Local and foreign models of reproduction in Nyanza Province, Kenya.

PMID- 18348361
TI  - From holy war to opium war? A case study of the opium economy in north eastern
      Afghanistan.

PMID- 18348362
TI  - Convention on the Rights of Persons with Disabilities.

PMID- 18348363
TI  - Dr. Duane Frederick Bruley.

PMID- 18348364
TI  - Dr. Britton Chance.

PMID- 18348365
TI  - Formidable management.

PMID- 18348366
TI  - Non-traditional analgesics for dental pain.

PMID- 18348367
TI  - Reparative dentistry or restorative dentistry?
AB  - The real definition of restorative dentistry is found in the heart and hands of
      each individual restorative dentist. His or her training, continuing dental
      education, mentors, needs (financial and emotional), and style of practice all
      help to develop a philosophy of dental practice that affects daily restorative
      decisions. Depending on the factors described above, the decision to repair a
      tooth or change the environment and restore the tooth to a different shape, size,
      or color also may change. In recent years, patients' esthetic desires have become
      more of a factor than they were in previous decades. There are no exact written
      tn-stone definitions of restorative dentistry, since the answers are operator
      dependent and can vary. This column is meant to be food for thought and perhaps
      inspire discussion when dentists assemble for meetings or study clubs with the
      goal of delivering longer-lasting dentistry through a restorative dental
      practice.

PMID- 18348368
TI  - Physical and oral characteristics of Crouzon syndrome, Apert syndrome, and Pierre
      Robin sequence.

PMID- 18348369
TI  - Topographic and radiographic profile assessment of dental erosion. Part II:
      effect of citrus fruit juices on human dentition.
AB  - This study sought to monitor changes in the topography, morphology, and
      radiographic profiles of human permanent teeth that had been exposed to citrus
      fruit juices. The effect of long-term exposure was monitored for a prolonged
      duration of 20 weeks according to set criteria. Topographic and morphologic
      changes were observed at weekly intervals following challenge by test fluids
      (orange, lemon, and grapefruit juices) and compared with control fluids (acetic
      acid and water). The qualitative changes in the specimens' topography and the
      morphology of citrus fruit juices and control fluids are described as a function
      of time, in specific details. The digitized radiographic images obtained at four
      week intervals were analyzed and the changes were assessed. The results indicated
      that orange juice specimens demonstrated the mildest changes, while lemon juice
      specimens displayed the most severe damage to the coronal segments of the teeth.
      This damage manifested as loss of cusp height, cervical enamel, and coronal
      radius, as well as reduction of enamel cap height. Of the tested and control
      fluids, lemon juice displayed the most eros ion, followed by acetic acid,
      grapefruit juice, orange juice, and water, which had no effect. Continued
      immersion in the four acidic fluids led to varying degrees of enamel loss
      progression.

PMID- 18348370
TI  - Microhardness of different thicknesses of resin composite polymerized by
      conventional photocuring at different distances.
AB  - This in vitro study sought to evaluate the influence of photocuring modes and
      polymerization time on the microhardness of a hybrid composite resin. Sixty
      composite resin specimens were prepared at random and divided into 12
      experimental groups (n=5), consisting of four curing tip distances (2.0 mm, 4.0
      mm, 6.0 mm, and 8.0 mm) and three sample thicknesses (0.5 mm, 1.0 mm, and 2.0
      mm). All samples were polymerized with a continuous output at 550 mW/cm2. After
      24 hours, Knoop microhardness measurements were obtained on top and bottom
      surfaces of the sample, with a load of 25 g for 10 seconds. Five indentations
      were made on each surface of each sample. Subdivided parcels ANOVA test and Tukey
      test were performed (p = 0.05). There were no statistical differences among the
      experimental groups for the top surface. On the bottom surface, 0.5 mm and 1.0 mm
      sample thicknesses showed significantly higher hardness means for all photocuring
      tip distances when compared with the 2.0 mm sample thickness. In terms of the
      photocuring tip distance, the 2.0 mm and 4.0 mm distances showed significantly
      higher hardness means for all sample thicknesses when compared with the 8.0 mm
      distance. For all experimental conditions, the top surface showed higher hardness
      than the bottom surface. It was concluded that the resin composite increments
      should be decreased to improve the polymerization of the resin composite bottom
      surface in deep cavities.

PMID- 18348371
TI  - A mandibular surgical training model.
AB  - Performing surgical procedures on the mandible can present many challenges due to
      the anatomy and the limited access available to the various areas of the
      mandibular arch. The experience of the surgeon and the complexity of the surgery
      must be considered before attempting treatment. A static mandibular training
      model provides dentists with the opportunity to practice multiple surgical
      procedures to develop the skills that are necessary to treat patients competently
      and comprehensively. The mandible's unique anatomy presents a number of
      challenges when performing surgical procedures. A surgical model that makes it
      possible to practice multiple techniques benefits the surgeon by building the
      confidence to attempt more complex surgical procedures and thus provide patients
      with additional treatment options. This mandibular surgical model serves as a
      learning tool and provides an avenue for learning different surgical techniques
      that may be performed in various areas of the mandible. A number of procedures
      can be performed on the model, including the extraction of third molars, incision
      and drainage of a vestibular/buccal swelling, excisional biopsy of intrabony
      lesions, tori removal, initial implant alignment procedures, and suturing/flap
      designs. A number of these procedures can be performed on one model.

PMID- 18348372
TI  - Comparison of the success of root canal therapy in HIV/AIDS patients and non
      infected controls.
AB  - This study compared the rate of successful endodontic treatments between two
      cohorts of patients with similar teeth, one group with HIV/AIDS and one without.
      A retrospective chart review was performed on two cohorts, with 50 teeth in each
      cohort. There was no statistically significant difference in endodontic success
      between the two groups. The failure groups were small, with no significant
      trends.

PMID- 18348373
TI  - An alternative and simplified technique for the impression of completely
      edentulous ridges.
AB  - When a patient's original denture is in harmony with the anatomicand physiologic
      limitations of the oral structures, itcan be used a an impression tray for making
      a new denture. This article describes this alternative technique and illustrates
      the steps involved to demonstrate the denture adaptation and provide patient
      satisfaction.

PMID- 18348374
TI  - Effects of surface treatments and storage times on the tensile bond strength of
      adhesive cements to noble and base metal alloys.
AB  - This work evaluated two resin cements and a glass-ionomer cement and their bond
      strength to gold-palladium (Au-Pd), silver-palladium (Ag-Pd), and nickel-chromium
      beryllium (Ni-Cr-Be) alloys, utilizing three surface treatments over a period of
      six months. Eight hundred ten pieces were cast (in a button shape flat surfaces)
      in one of three alloys. Each alloy group was assigned to three other groups,
      based on the surface treatment utilized. Specimens were fabricated by bonding
      similar buttons in using one of three adhesive cements. The 405 pairs were
      thermocycled and stored in saline solution (0.9% NaCl) at 37 degrees C. The
      tensile bond strengths were measured in a universal testing machine after storage
      times of 2, 90, or 180 days. The highest mean bond strength value was obtained
      with the base metal alloy (10.9 +/- 8.6 MPa). In terms of surface treatment,
      oxidation resulted in the highest mean bond strength (13.7 +/- 7.3 MPa), followed
      by sandblasting (10.3 +/- 5.5 MPa) and polishing (3.0 +/- 6.4 MPa). Panavia Ex
      (13.2 +/- 9.3 MPa) showed significantly higher bond strengths than the other two
      cements, although the storage time reduced all bond strengths significantly.

PMID- 18348375
TI  - Understanding the autistic dental patient.
AB  - Autism spectrum disorder (ASD) is one of many pervasive developmental disorders
      (PDD); others include Rett syndrome, childhood disintegrative disorder (also
      known as Heller's syndrome), pervasive developmental disorder not otherwise
      specified (PDD-NOS), and the higher functioning Asperger's syndrome. Because ASD
      is the most common of the developmental disabilities, it is not unusual for
      dentists to have ASD patients among their patient population. As the name
      indicates, ASD varies widely in its clinical manifestations; however, dentists
      are likely to encounter difficulties with communication and socialization.
      Although communication may be difficult, it is not impossible. A thorough
      understanding of this complex neurological disorder and displaying patience are
      vital for the dentist. This article seeks to familiarize readers with ASD
      characteristics and co-morbid conditions that may affect dental treatment and
      provide some management strategies for this unique population.

PMID- 18348376
TI  - Oral lipoma: report of three cases.
AB  - Oral lipomas are benign lesions that are seen infrequently in the dental
      practice. This article details the clinical and histopathologic findings of three
      cases of intraoral lipomas. All of the lesions exhibited a yellow color. Two of
      the tumors were located on the buccal mucosa, while the other mass arose on the
      mandibular buccal/labial vestibule, was considerably larger in size, produced
      extraoral swelling, and necessitated a preoperative MRI due to close
      approximation to the mental nerve. None of the patients elicited any history of
      attendant symptomatology. Excisional biopsies in each case revealed well
      circumscribed masses surrounded by a thin fibrous capsule and composed of sheets
      of mature adipocytes arranged in a "chicken wire" configuration. The tumor
      adipocytes were similar to normal adult fat cells and contained a small,
      uniformly eccentric nucleus with a single, clear cytoplasmic vacuole. Surgical
      excision is the modality of treatment and malignant transformation or recurrence
      is rare.

PMID- 18348377
TI  - Parental behavior regarding traumatically avulsed teeth: case reports.
AB  - The prognosis for an avulsed tooth depends primarily on appropriate emergency
      management, which usually must be provided by lay people prior to the child's
      initial dental contact. As immediate replantation is considered the best therapy
      for an avulsed tooth in permanent dentition, parents should be made aware of
      first aid procedures for this situation. This article describes three cases
      involving avulsed teeth in children and discusses the parents' approaches
      concerning emergency procedures.

PMID- 18348378
TI  - Unusual presentation of idiopathic osteosclerosis: a case report.
AB  - Idiopathic osteosclerosis (IO) typically manifests as an incidentally discovered,
      well-defined homogenous radiopacity that blends in with the surrounding bone.
      Once the condition is diagnosed, treatment is neither indicated nor necessary;
      however, atypical variants of osteosclerosis have been described and may pose a
      diagnostic and management dilemma for the clinician who encounters them. This
      case report discusses the differential conditions that should be considered when
      an atypical variant of IO is encountered. While the diagnosis in this case was
      fortuitously confirmed by biopsy, routine follow-up is the recommended course of
      action.

PMID- 18348379
TI  - Florid cemento-osseous dysplasia: a report of three cases.
AB  - Florid cemento-osseous dysplasia (FCOD) is a non-neoplastic condition of the jaws
      that is not associated with inflammation of the pulp or periodontal tissue. This
      article reports on three cases that were diagnosed as FCOD, demonstrating the
      importance of both clinical and radiographic diagnosis and the clinical
      management of these lesions.

PMID- 18348380
TI  - An unusual manifestation of actinomycosis infection of the maxilla.
AB  - Postoperative actinomycosis infection caused by Actinomyces israelii is uncommon.
      Cervicofacial actinomycosis may appear as an opportunistc infection in the oral
      cavity. Initial diagnosis of this condition is difficult after oral surgery and
      the condition often is mistaken for more common odontogenic infections.
      Actinomycosis responds to antibiotic therapy but the condition recurs after
      therapy is discontinued. This article presents an unusual case of postsurgical
      actinomycosis that manifested in the cheek and appeared to be unrelated to the
      surgical extraction of an impacted maxillary third molar that had occurred one
      year earlier. The organism was sampled under anaerobic conditions, isolated, and
      diagnosed by Gram's stain and culture tests. The condition was cured after
      extraoral surgical drainage, debridement, and several months of oral antibiotic
      administration.

PMID- 18348381
TI  - Obturation with heat and vibration: the DownPak device.
AB  - Achieving successful endodontic treatment requires an accurate diagnosis and
      appropriate cleaning, shaping, and three-dimensional obturation of the canals.
      This article describes a new obturation technique that utilizes a warm plugger or
      spreader, delivered (in conjunction with vibration) with a single cordless
      device, the DownPak.

PMID- 18348382
TI  - Severe phenytoin-induced gingival enlargement associated with periodontitis.
AB  - The potential of phenytoin to induce gingival hyperplasia has been well
      established. High levels of dental plaque and calculus have been reported as a
      critical co-factor for the development and severity of phenytoin-induced gingival
      hyperplasia. This article documents a severe gingival enlargement associated with
      periodontitis (in a patient under combined anti-epileptic therapy) and provides a
      rational model for its clinical management. Initially, full-mouth scaling and
      root planing, oral hygiene instructions, and phenytoin withdrawal were performed;
      however, clinical results demonstrated partial resolution of maxillary gingival
      hyperplasia. Subsequently, surgical therapy was indicated for the maxillary
      teeth. Complete reduction of gingival enlargement and improvement of clinical
      periodontal parameters were observed after the surgical therapy. This case report
      clearly describes the challenges that oral and medical health practitioners face
      when developing appropriate prevention and treatment programs for epileptic
      patients, particularly those with periodontal disease.

PMID- 18348383
TI  - A controlled trial of a dissolving oral patch concerning glycyrrhiza (licorice)
      herbal extract for the treatment of aphthous ulcers.
AB  - Recurrent aphthous ulcers (RAU) are a common and painful condition. This article
      describes a randomized, double-blind clinical trial of an over-the-counter
      medicated intraoral adhesive patch for treatment of RAU. Subjects were randomly
      assigned to either an active drug (patch with extract of glycyrrhiza root) or
      placebo patch treatment group (both n=23) at onset of a lesion. Lesion size and
      pain report (unstimulated and stimulated) were assessed at intervals. A no
      treatment group (n=23) also was recruited and assessed similarly. By the eighth
      day, the ulcer size for the active treatment group was significantly lower (p <
      0.05), while the By the fourth day, the active treatment group lesions in the no
      treatment group increased 13% from baseline.reported significantly less pre
      stimulus pain (p < 0.01); at this point, 81% of this group reported no pre
      stimulus pain, comp ared with 63% of the placebo patch group and 40% of the no
      treatment group

PMID- 18348384
TI  - Hard swelling in the right mandible. Ameloblastoma.

PMID- 18348385
TI  - Sloughing and blistering of the gingiva. Pemphigoid.

PMID- 18348386
TI  - The problem of invisibility--fees edition.

PMID- 18348387
TI  - Shipshape: sanitation inspections on cruise ships, 1990-2005, Vessel Sanitation
      Program, Centers for Disease Control and Prevention.
AB  - In the course of a successful collaboration between the Centers for Disease
      Control and Prevention (CDC) and the cruise ship industry on reducing common
      source outbreaks, CDC's Vessel Sanitation Program (VSP) has expanded its
      training, education, and cruise ship inspection programs. The study reported here
      evaluated 15 years of ship sanitation inspection data from the National Center
      for Environmental Health and assessed performance in specific sanitation
      categories from 1996 to 2005. During the period 1990-2005, scores from cruise
      ship environmental sanitation inspections steadily improved. The percentage of
      inspections with violations decreased among five of nine categories. Those five
      categories were Washing Facilities, Contact Surfaces, Facility Maintenance, Food
      Handling, and Communicable Disease Practices. Inspection violations increased
      proportionally in the categories of Swimming Pools and Water System
      Protection/Chart Recording. Overall continued good performance in most sanitation
      categories is likely attributable to on-site training during inspections,
      improvements in ship construction, and a switch from hot-holding temperatures to
      time limits as a public health control for foods on display.

PMID- 18348388
TI  - Determination of the feasibility of using a portable X-ray fluorescence (XRF)
      analyzer in the field for measurement of lead content of sieved soil.
AB  - Soil samples collected in housing areas with potential lead contamination
      generally are analyzed with flame atomic absorption spectrometry (FAAS) or other
      laboratory methods. Previous work indicates that field-portable X-ray
      fluorescence (XRF) analysis is capable of detecting soil lead levels comparable
      to those detected by FAAS in samples sieved to less than 125 microm in a
      laboratory. A considerable savings, both economical and in laboratory reporting
      time, would occur if a practical field method could be developed that does not
      require laboratory digestion and analysis. The XRF method also would provide
      immediate results that would facilitate the provision of information to residents
      and other interested parties more quickly than is possible with conventional
      laboratory methods. The goal of the study reported here was to determine the
      practicality of using the field-portable XRF analyzer for analysis of lead in
      soil samples that were sieved in the field. The practicality of using the XRF was
      determined by the amount of time it took to prepare and analyze the samples in
      the field and by the ease with which the procedure could be accomplished on site.
      Another objective of the study was to determine the effects of moisture on the
      process of sieving the soil. Seventy-eight samples were collected from 30
      locations near 10 houses and were prepared and analyzed at the locations where
      they were collected. Mean soil lead concentrations by XRF were 816 ppm before
      drying and 817 ppm after drying, and by laboratory FAAS were 1,042 ppm.
      Correlation of field-portable XRF and FAAS results was excellent for samples
      sieved to less than 125 microm, with R2 values of .9902 and .992 before and after
      drying, respectively. The saturation ranged from 10 percent to 90 percent. At 65
      percent saturation or higher, it was not feasible to sieve the soil in the field
      without a thorough drying step, since the soil would not pass through the sieve.
      Therefore the field method with sieving was not practical when the soil was 65
      percent or more saturated unless a time-consuming drying process was included.

PMID- 18348389
TI  - Survival and growth of foodborne microorganisms in processed and individually
      wrapped cheese slices.
AB  - The objectives of the research reported here were to determine the growth,
      survival, or inactivation of selected microorganisms on individually wrapped
      processed cheese (IWC) slices stored at 5 degrees C and 22 degrees C, and to
      compare quality indices. IWC slices were spot-inoculated with foodborne
      pathogenic bacteria (Listeria monocytogenes, Staphylococcus aureus, and
      Salmonella spp.), spoilage bacteria (Pseudomonas spp. and Lactobacillus spp.),
      and spoilage molds (Penicillium spp. and Cladosporium spp.). Each bacterium was
      inoculated at 10(5) CFUs/g for determination of growth, survival, or
      inactivation. Molds were inoculated at 10(2) spores per gram and observed for
      growth. Fifty percent of the inoculated product samples were held at 5 degrees C
      (to simulate refrigeration), and the other 50 percent were held at 22 degrees C
      (to simulate ambient temperature) throughout shelf life. Samples taken on days 0,
      3, 7,10, 14, and 28 and after 2, 3, 6, and 9 months, and were evaluated for
      surviving cells (by means of appropriate selective media), color (with the cheese
      color guide), and lipid oxidation (by means of peroxide values). Bacterial
      inactivation was observed in all conditions. At 14 days, a 5-log reduction was
      observed for Listeria monocytogenes and Salmonella, while a 3-log reduction was
      observed for Staphylococcus aureus. For Pseudomonas spp. and Lactobacillus spp.,
      a 2-log reduction was observed within 3 days, with an additional 1-log reduction
      noted after several months. Mold levels showed no change during the first several
      weeks of storage. At 84 days, mold levels decreased at 5 degrees C, but they
      showed growth at 22 degrees C, to approximately 10(5) CFUs/g. Visual color was
      evaluated on a 10-point National Cheese Institute scale. During storage at 5
      degrees C or 22 degrees C, color became darker and values increased from 4 to 5
      and 4 to 7, respectively. Higher peroxide values were also obtained for the
      samples held at 22 degrees C versus 5 degrees C. From a microbiological
      standpoint, pathogenic and spoilage bacteria were unable to grow in this product;
      however, long-term storage at 22 degrees C led to lower product quality and mold
      growth.

PMID- 18348390
TI  - NEHA position regarding the sale or distribution of raw milk.

PMID- 18348391
TI  - Antimicrobial resistance in Escherichia coli isolated in wastewater and sludge
      from poultry slaughterhouse wastewater plants.
AB  - The authors investigated the antimicrobial resistance of Escherichia coli
      isolates in 22 samples of crude inflow, treated effluent, and sludge collected at
      the wastewater treatment plants of eight poultry slaughterhouses in Portugal. A
      total of 549 E. coli strains were recovered and tested for resistance to 12
      antimicrobial agents. Multidrug resistance was present in 55.7 percent of the
      isolates. Resistance to tetracycline, ampicillin, trimethoprim/sulfamethoxazole,
      streptomycin, and enrofloxacin was found in 80.7 percent, 56.5 percent, 47.5
      percent, 39.2 percent, and 18.4 percent of the isolates, respectively. Resistance
      rates of E. coli to nearly all of the tested antibiotics were higher in the
      strains obtained from the six slaughterhouses that handled conventional broilers
      than in the two slaughterhouses that handled free-range broilers. Wastewater
      treatment resulted in an E. coli decrease of between 0.5 log and 3 log;
      nevertheless, an average of 5.2 x 10(5) CFUs/100 mL were present in the outflow
      of the plants. These data indicate that the use of antimicrobials in poultry
      production leads to the selection of a large pool of resistance genes and that
      wastewater treatment processes are unable to inactivate the bacteria and thus
      will result in dissemination of resistant E. coli into the environment.

PMID- 18348392
TI  - A novel technology to improve drinking water quality using natural treatment
      methods in rural Tanzania.
AB  - It is estimated that one billion people worldwide do not have access to treated
      drinking water. This paper reports on an investigation into the potential of
      indigenous or natural water treatment methods as alternatives to conventional
      chemical water treatment methods. The seeds of five natural plant species--Vigna
      unguiculata, Phaseolus mungo, Glycine max, Pisum sativam, and Arachis hypogea-
      were evaluated for the removal of turbidity, and their efficiency was compared
      with that of alum. The use of a solar energy-saving method to disinfect drinking
      water--leaving it to heat under the sun to reduce bacteria colonies--also was
      evaluated, The study revealed that for raw water with turbidity of 482
      nephelometric turbidity units, coagulation with seed extracts from natural plant
      species reduced natural turbidity by 96.7 to 100 percent when the seed extract
      was used as the primary coagulant and by 100 percent when it was used as a
      coagulant aid. The study showed further that natural coagulants were as effective
      as commercial alum [Al2(SO4)3] and even superior for clarification because the
      optimum dosage was low compared with that of alum. Leaving samples of water
      clarified by natural coagulants on a black-painted roof for 8 hours achieved up
      to 100 percent bacteria kill.

PMID- 18348393
TI  - Web-based resources for environmental public health practitioners.

PMID- 18348394
TI  - U.S. EPA's Indoor Air Quality programs and CARE.

PMID- 18348395
TI  - Groundwater awareness: a matter of public health.

PMID- 18348396
TI  - Biomedicine in Edinburgh, 1887-1920.
AB  - This paper examines the scientific work of the Laboratory of the Royal College of
      Physicians of Edinburgh from its foundation in 1887 to 1920. It looks in
      particular at the pivotal role of clinical cases in the work of the Laboratory,
      using the concept of 'triangulation' to analyse how cases served both as objects
      of scientific knowledge and as sites for articulating and aligning the concerns
      of medical practitioners and career scientists. It goes on to propose a general
      model for thinking about the role of cases in scientific knowledge production,
      based on a rereading of Kuhn as seen through the lens of the sociology of
      scientific knowledge. It concludes with some general reflections on how this
      analysis of the work of the Laboratory helps us to rethink the relations between
      basic and applied medical science in the period before the emergence of modern
      biomedicine.

PMID- 18348397
TI  - From eugenics to scientometrics: Galton, Cattell, and men of science.
AB  - In 1906, James McKeen Cattell, editor of Science, published a directory of men of
      science. American Men of Science was a collection of biographical sketches of
      thousands of men of science in the USA and was published periodically. It
      launched, and was used in, the very first systematic quantitative studies on
      science. Cattell used two concepts for his statistics: productivity, defined as
      the number of men of science a nation produces, and performance or merit, defined
      as scientific contributions to research as judged by peers. These are the two
      dimensions that still define measurement of scientific productivity today:
      quantity and quality. This paper analyzes the emergence of statistics on science
      and the very first uses to which they were put. It argues that the measurement of
      science emerged out of interest in great men, heredity and eugenics, and the
      contribution of eminent men to civilization. Among these eminent men were men of
      science, the population of whom was thought to be in decline and insufficiently
      appreciated and supported. Statistics on men of science thus came to be collected
      to document the case, and to contribute to the advancement of science and the
      scientific profession.

PMID- 18348398
TI  - Inbreeding, eugenics, and Helen Dean King (1869-1955).
AB  - Helen Dean King's scientific work focused on inbreeding using experimental data
      collected from standardized laboratory rats to elucidate problems in human
      heredity. The meticulous care with which she carried on her inbreeding
      experiments assured that her results were dependable and her theoretical
      explanations credible. By using her nearly homozygous rats as desired
      commodities, she also was granted access to venues and people otherwise
      unavailable to her as a woman. King's scientific career was made possible through
      her life experiences. She earned a doctorate from Bryn Mawr College under Thomas
      Hunt Morgan and spent a productive career at the Wistar Institute of Anatomy and
      Biology in Philadelphia where she had access to the experimental subjects which
      made her career possible. In this paper I examine King's work on inbreeding, her
      participation in the debates over eugenics, her position at the Wistar Institute,
      her status as a woman working with mostly male scientists, and her involvement
      with popular science.

PMID- 18348399
TI  - Aquaculture solids management using a combination of sand/gravel or unwoven
      fabric bed with Lolium perenne Lam as a plant biofilter.
AB  - OBJECTIVE: This work is an evaluation of the efficiency of a sand-gravel or
      unwoven fabric bed system and Lolium perenne Lam as plant biofilter in the
      reduction of solids and nutrients removal from aquaculture discharge water.
      METHODS: The first step consisted of the collection of wastewater in the tank and
      the distribution at three different hydraulic loading regimes (0.5, 1, 1.5
      L/hour) to the different experimental systems. The second step was to evaluate
      the performance of the different systems. The first system consisted of a bucket
      filled with a substrate of sand/gravel (20 cm in depth), on the bottom of which
      was a 80 mesh/inch2 of nylon (S1); the second was similar, but was planted with
      Lolium perenne lam (S2); the third was planted with a grass plate consisting of 7
      layers of unwoven fabric planted with L perenne (S3). RESULTS: The second system
      showed the best performance in reducing solids as well as in nutrients (TN, TP,
      and COD) reduction. The removal rates for TS, TN, and TP were negatively
      correlated with the loading regimes, with 0.5 L/hour being the most efficient and
      thus taken as the reference. CONCLUSIONS: Solids management using a sand/gravel
      substrate as bed culture and Lolium perenne L. as plant biofilter has proved to
      be an efficient technique for solids reduction with low operating cost. This
      grass plays an important role in wastewater eco-treatment by absorbing dissolved
      pollutants (TAN) as nutrients for its growth.

PMID- 18348400
TI  - Pleiotropic effect of tatC mutation on metabolism of pathogen Yersinia
      enterocolitica.
AB  - OBJECTIVE: To analyze the impact of depletion of the twin arginine translocation
      (TAT) system on virulence and physiology of Yersinia enterocolitica for a better
      understanding of its pathogenicity. METHODS: We constructed a DeltatatC::SpR
      mutant of Yersinia enterocolitica by P1 phage mediated transduction using
      Escherichia coli K-12 DeltatatC::SpR strain as a donor. RESULTS: A P1-mediated
      genetic material transfer was found between the two species of enterobacteria,
      indicating a great potential of acquisition of antibiotic resistance in emergency
      of a new threatening pathogen by genetic material exchanges. Periplasmic
      trimethylamine N-oxidase reductase activity was detected in the wild type Y.
      enterocolitica strain and translocation of this enzyme was completely abolished
      by the DeltatatC::SpR mutation. In addition, the DeltatatC::SpR mutation showed a
      pleiotropic effect on the metabolism of Y. enterocolitica. However, the tat
      mutation did not seem to affect the mobility and virulence of Y. enterocolitica
      under the conditions used. CONCLUSION: Unlike other pathogenic bacteria studied,
      the TAT system of Y. enterocolitica might play an important role in the
      pathogenic process, which is distinct from other pathogens, such as Pseudomonas
      aeruginosa and enterohemorrhagic E. coli O157:H7.

PMID- 18348401
TI  - Isolation and characterization of a new heterotrophic nitrifying Bacillus sp.
      strain.
AB  - OBJECTIVE: To characterize the heterotrophic nitrifying bacteria. METHODS: The
      bacteria were isolated from membrane bioreactor for treating synthetic wastewater
      using the method newly introduced in this study. Fluorescence in situ
      hybridization (FISH) was used to validate the nonexistence of autotrophic ammonia
      oxidizers and nitrite oxidizers. Batch tests were carried out to investigate the
      capability of heterotrophic nitrification by the pure culture. Phylogenetic
      analysis of the pure culture was performed. RESULTS: A heterotrophic nitrifier,
      named Bacillus sp. LY, was newly isolated from the membrane bioreactor system in
      which the efficiency of TN removal was up to 80%. After 24-day, incubation, the
      removal efficiency of COD by Bacillus sp. LY was 71.7%. The ammonium nitrogen
      removal rate after assimilation nearly ceased by Bacillus sp. LY was 74.7%. The
      phylogenetic tree of Bacillus sp. LY and the neighbouring nitrifiers were given.
      CONCLUSIONS: The batch test results indicate that Bacillus sp. LY can utilize the
      organic carbon as the source of assimilation when it grows on glucose and
      ammonium chloride medium accompanying the formation of oxidized-nitrogen. It also
      can denitrify nitrate while nitrifying. Bacillus sp. LY may become a new
      bacterial resource for heterotrophic nitrification and play a bioremediation role
      in nutrient removal.

PMID- 18348402
TI  - Effect of X-rays on expression of caspase-3 and p53 in EL-4 cells and its
      biological implications.
AB  - OBJECTIVE: To investigate the effect of X-rays on expression of caspase-3 and p53
      protein in EL-4 cells and its implications in induction of apoptosis and
      polyploid cells. METHODS: Mouse lymphoma cell line (EL-4 cells) was used.
      Fluorescent staining and flow cytometry analysis were employed for measurement of
      protein expression, apoptosis, cell cycle, and polyploid cells. RESULTS: The
      expression of caspase-3 protein increased significantly at 8 h and 12 h, compared
      with that of sham-irradiated control (P<0.05, respectively) and the expression of
      p53 protein increased significantly at 2, 4, 8, 12, and 24 h, compared with that
      of sham-irradiated control (P<0.05-P<0.01) in EL-4 cells after 4.0 Gy X
      irradiation. Apoptosis of EL-4 cells was increased significantly at 2, 4, 8, 12,
      24, 48, and 72 h after 4.0 Gy exposure, compared with that of sham-irradiated
      control (P<0.05-P<0.001). G2 phase cells were increased significantly at 4, 8,
      12, 24, 48, and 72 h (P<0.05-P<0.001). However, no marked change in the number of
      8 C polyploid cells was found from 2 to 48 h after 4.0 Gy exposure. CONCLUSION:
      The expressions of caspase-3 and p53 protein in EL-4 cells are induced by X-rays,
      which might play an important role in the induction of apoptosis, and the
      molecular pathway for polyploid formation might be p53-independent.

PMID- 18348403
TI  - Application of benchmark dose (BMD) in estimating biological exposure limit (BEL)
      to cadmium.
AB  - OBJECTIVE: To estimate the biological exposure limit (BEL) using benchmark dose
      (BMD) based on two sets of data from occupational epidemiology. METHODS: Cadmium
      exposed workers were selected from a cadmium smelting factory and a zinc product
      factory. Doctors, nurses or shop assistants living in the same area served as a
      control group. Urinary cadmium (UCd) was used as an exposure biomarker and
      urinary beta2-microgloburin (B2M), N-acetyl-13-D-glucosaminidase (NAG) and
      albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary
      creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate
      BMD. RESULTS: The cut-off point (abnormal values) was determined based on the
      upper limit of 95% of effect biomarkers in control group. There was a significant
      dose response relationship between the effect biomarkers (urinary B2M, NAG; and
      ALB) and exposure biomarker (UCd). BEL value was 5 microg/g creatinine for UB2M
      as an effect biomarker, consistent with the recommendation of WHO. BEL could be
      estimated by using the method of BMD. BEL value was 3 microg/g creatinine for
      UNAG as an effect biomarker. The more sensitive the used biomarker is, the more
      occupational population will be protected. CONCLUSION: BMD can be used in
      estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for
      estimating BEL after cadmium exposure.

PMID- 18348404
TI  - A cell-based high-throughput screening assay for Farnesoid X receptor agonists.
AB  - OBJECTIVE: To develop a high-throughput screening assay for Farnesoid X receptor
      (FXR) agonists based on mammalian one-hybrid system (a chimera receptor gene
      system) for the purpose of identifying new lead compounds for dyslipidaemia drug
      from the chemical library. METHODS: cDNA encoding the human FXR ligand binding
      domain (LBD) was amplified by RT-PCR from a human liver total mRNA and fused to
      the DNA binding domain (DBD) of yeast GAL4 of pBIND to construct a GAL4-FXR (LBD)
      chimera expression plasmid. Five copies of the GAL4 DNA binding site were
      synthesized and inserted into upstream of the SV40 promoter of pGL3-promoter
      vector to construct a reporter plasmid pG5-SV40 Luc. The assay was developed by
      transient co-transfection with pG5-SV40 Luc reporter plasmid and pBIND-FXR-LBD
      (189-472) chimera expression plasmid. RESULTS: After optimization, CDCA, a FXR
      natural agonist, could induce expression of the luciferase gene in a dose
      dependent manner, and had a signal/noise ratio of 10 and Z' factor value of 0.65.
      CONCLUSION: A stable and sensitive cell-based high-throughput screening model can
      be used in high-throughput screening for FXR agonists from the synthetic and
      natural compound library.

PMID- 18348405
TI  - Induction of apoptosis by recombinant soluble human TRAIL in Jurkat cells.
AB  - OBJECTIVE: To investigate the therapeutic potential of tumor necrosis factor
      (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily,
      and to analyze TRAIL-induced apoptosis in Jurkat cells. METHODS: Expression of
      TRAIL receptors (DR4 and DR5) was detected by reverse transcriptase-polymerase
      chain reaction (RT-PCR). Cytotoxic effects were determined by colony formation
      assay and a cell counting kit. The effects of recombinant TRAIL on apoptosis of
      Jurkat cells were determined by DNA fragmentation (DNA ladder) and PI staining.
      Changes in mitochondrial membrane potential were detected with JC-1 fluorescence.
      RESULTS: TRAIL inhibited the proliferation and induced internucleosomal DNA
      fragmentation (characteristic of apoptosis) and loss of mitochondrial membrane
      potential. CONCLUSION: Recombinant soluble TRAIL can be used as a therapy for
      cancer.

PMID- 18348406
TI  - Characteristics of Zn2+ biosorption by Saccharomyces cerevisiae.
AB  - OBJECTIVE: To investigate the characteristics of Zn2+ biosorption and the release
      of cations during the process of Zn2+ biosorption by intact cells of
      Saccharomyces cerevisiae. METHODS: The batch adsorption test was used to study
      the biosorption equilibrium and isotherm. Zn2+ concentration was measured with
      atomic adsorption spectrophotometer (AAS) AAS 6 Vario. RESULTS: When the initial
      concentration of Zn2+ ranged between 0.08 and 0.8 mmol/L, the initial pH was
      natural (about 5.65), the sorbent concentration was about 1 g/L and the capacity
      of Zn2+ biosorption was from 74.8 to 654.8 micromol/g. The pH value increased by
      0.55-1.28 and the intracellular cations (K+, Mg2+, Na+, Ca2+) of the cells were
      released during the process of Zn2+ biosorption. CONCLUSION: Ion exchange was one
      of the mechanisms for Zn2+ biosorption. The biomass of Saccharomyces cerevisiae
      is a potential biosorbent for the removal of Zn2+ from aqueous solution. More
      work needs to be done before putting it into practical application.

PMID- 18348407
TI  - Contamination of aflatoxins in different kinds of foods in China.
AB  - OBJECTIVE: To study the contamination of total aflatoxins (AFs) in different
      kinds of foods including corn, peanut, rice, walnut, and pine nut in six
      provinces and two municipalities in China. METHODS: A total of 283 samples of
      corn, peanut, rice, walnut and pine nut were randomly collected from local
      markets in Fujian, Guangdong, Guangxi, Hubei, Jiangsu, and Zhejiang provinces, as
      well as in Shanghai and Chongqing municipalities. The samples were ground to
      which acetonitrile/water solution was added. After filtering, the extract was
      transferred into a MycoSep purifying column and was pressed slowly. Then the
      purified liquid was derivatized with trifluoroacetic acid (TFA) and assayed using
      high performance liquid chromatography (HPLC). RESULTS: AFs were detected in
      70.27% of corn samples, with a mean level of 27.44 microg/kg and the highest
      level of 1098.36 microg/kg. In peanut, the AFs detection rate was 23.08%, with a
      mean level of 0.82 microg/kg and the highest level of 28.39 microg/kg. Very few
      rice samples with AFs were detected. The AFs levels were very low in walnut and
      pine nut. CONCLUSION: Corn is the food most seriously contaminated with AFs in
      China. AFB1 is the main aflatoxin which is found as a contaminant in foods.

PMID- 18348408
TI  - Isolation of human antibodies against hepatitis E virus from phage display
      library by immobilized metal affinity chromatography.
AB  - OBJECTIVE: To isolate human antibodies against hepatitis E virus from phage
      display library by a new method of panning phage antibody library based on
      immobilized metal affinity chromatography (IMAC). METHODS: Phage antibody library
      was allowed to mix with hex-His tagged expressed HEV specific antigen, NE2, in
      solution for adequate binding before affinity resin for hex-His was added. The
      non-specific phage antibodies were removed by extensive washing and the specific
      bound phage antibodies could then be eluted to infect TG1 or repeat the binding
      process for subsequent rounds of purification. The specificity of the selected
      human antibodies were tested by antigen competitive ELISA, human sera blocking
      ELISA, scFv expression, and sequence analysis. RESULTS: His-NE2 specific
      recombinant phages were successfully enriched after panning procedure. Two
      individual phage clones, 126 and 138, showed 50% inhibition in NE2 antigen
      competition ELISA and obvious blocking effect by HEV positive serum in blocking
      ELISA. Soluble scFv of 126, 138 bound to NE2 specifically. CONCLUSION: Two
      specific human phage antibodies against hepatitis E virus (HEV) from phage
      display library were isolated by immobilized metal affinity chromatography. The
      immobilized metal affinity chromatography applied to phage antibody selection was
      a helpful supplement to the selection in solution.

PMID- 18348409
TI  - Tetrandrine: a potent abrogator of G2 checkpoint function in tumor cells and its
      mechanism.
AB  - OBJECTIVE: To assess the ability of tetrandrine (Tet) to enhance the sensitivity
      to irradiation and its mechanism in cell lines of human breast cancer p53-mutant
      MCF-7/ADR, p53-wild-type MCF-7 and human colon carcinoma p53-mutant HT-29 as well
      as in C26 colorectal carcinoma-bearing BALB/c mice. METHODS: MCF-7/ADR, HT-29 and
      MCF-7 cells were exposed to irradiation in the absence or presence of
      tetrandrine. The effect of Tet on the cytotoxicity of X-irradiation in these
      three cells was determined and the effect of tetrandrine on cell cycle arrest
      induced by irradiation in its absence or presence was studied by flow cytometry.
      Moreover, mitotic index measurement determined mitosis of cells to enter mitosis.
      Western blotting was employed to detect cyclin B 1 and Cdc2 proteins in extracts
      from irradiated or non-irradiated cells of MCF-7/ADR, HT-29 and MCF-7 treated
      with tetrandrine at various concentrations. Tumor growth delay assay was
      conducted to determine the radio-sensitization of tetrandrine in vivo. RESULTS:
      Clonogenic assay showed that tetrandrine markedly enhanced the lethal effect of X
      rays on p53-mutant MCF-7/ADR and HT-29 cells and the sensitization enhancement
      ratio (SER) of tetrandrine was 1.51 and 1.63, but its SER was only 1.1 in p53-wt
      MCF-7 cells. Irradiated p53-mutant MCF-7/ADR and HT-29 cells were only arrested
      in G2/M phase while MCF-7 cells were arrested in G1 and G2/M phases. Radiation
      induced G2 phase arrests were abrogated by tetrandrine in a concentration
      dependent manner in MCF-7/ADR and HT-29 cells, whereas redistribution within MCF
      7 cell cycle changed slightly. The proportion of cells in M phase increased from
      1.3% to 14.7% in MCF-7/ADR cells, and from 1.5% to 13.2% in HT-29 cells, but 2.4%
      to 7.1% in MCF-7 cells. Furthermore, the levels of cyclin B 1 and Cdc2 expression
      decreased after X-irradiation in MCF-7/ADR and HT-29 cells, and the mitotic index
      was also lower. Tet could reverse the decrease and induce the irradiated cells to
      enter mitosis (M phase). Endosomatic experiment showed that tetrandrine caused
      tumor growth delay in irradiated mice. CONCLUSION: Tetrandrine boosts the cell
      killing activity of irradiation both in vitro and in vivo. Tetrandrine is a
      potent abrogator for G2 checkpoint control and can sensitize the cells to
      radiation.

PMID- 18348410
TI  - Interaction between ambient particles and ozone and its effect on daily
      mortality.
AB  - OBJECTIVE: To examine the effect of particulate matter (PM) less than 10 microns
      in diameter (PM10) and ozone (O3) on daily mortality in Shanghai, China. METHODS:
      A generalized additive model with penalized spline function was used to observe
      the acute effect of PM10 and O3 on daily mortality. RESULTS: Higher PM10
      significantly increased the effect of O3 on total mortality, and O3 also
      increased the effect of PM10 although the estimated increment was statistically
      insignificant. CONCLUSION: Our findings provide further evidence for the effect
      of PM10 and O3 on daily mortality.

PMID- 18348411
TI  - HLA-DM polymorphism and risk of trichloroethylene induced medicamentosa-like
      dermatitis.
AB  - OBJECTIVE: To establish the association between genetic polymorphisms of HLA-DMA
      and HLA-DMB and risk of developing trichloroethylene-induced medicamentosa-like
      dermatitis (TIMLD). METHODS: Sixty-one cases were medically confirmed to have
      been affected with TIMLD and 60 controls were selected from exposed workers who
      were free from TIMLD. The TIMLD cases and controls were similar in terms of age,
      sex, and duration of exposure. DNA was extracted both from the TIMLD cases and
      controls, HLA-DMA and HLA-DMB loci were amplified by using Touchdown PCR, and the
      alleles and genotypes were confirmed by restriction fragment length polymorphism
      (RFLP) and direct sequencing. Finally, the frequencies of HLA-DMA and HLA-DMB
      variants were compared between the two groups. RESULTS: The results showed that
      the frequency of HLA-DMA*0101 and HLA-DMB*0103 alleles was significantly
      increased in TIMLD patients than in controls (71.3% vs. 55.0% for HLA-DMA*0101;
      P<0.05) (11.5% vs. 3.3% for HLA-DMB*0103; P<0.05). In addition, the frequency of
      HLA-DMA*0102-*0102 homozygous genotype was also significantly higher in the
      controls than in the patients (25.0% vs. 8.2%, P<0.05), whereas the frequency of
      heterozygous HLA-DMB *0101-*0102 genotype was lower in the patients in comparison
      with the controls. Conclusion The polymorphisms of HLA-DM may be associated with
      the susceptibility to TIMLD.

PMID- 18348412
TI  - Evaluation of two anti-hepatitis E virus IgM kits.
AB  - OBJECTIVE: To evaluate two commercial anti-hepatitis E virus (HEV) IgM kits used
      for differential diagnosis of acute enteric viral hepatitis. METHODS: The kit for
      IgM capture assay, was produced with a recombinant HEV structural protein
      protecting primates against experimental infection by different HEV genotypes,
      while the other kit for indirect ELISA was produced with recombinant structural
      proteins from different HEV genotypes. The serum specimens were taken from 241
      cases with a confirmed or presumptive diagnosis of hepatitis A and 74 cases with
      a confirmed or presumptive diagnosis of hepatitis E. RESULTS: The sensitivity and
      specificity of the IgM capture assay kit were 97% and 100%, respectively, and the
      corresponding values for the other kit were 70% and 78%, respectively.
      CONCLUSION: The IgM capture assay kit has higher sensitivity and specificity in
      diagnosing acute enteric viral hepatitis E.

PMID- 18348413
TI  - What more do we need to know for a world without violence?
AB  - Violence, a universal health issue, presents serious implications for general
      health and interpersonal relations. Roots of violence appear in early childhood
      and instances of extreme violence may become apparent in adolescence. Serious
      antisocial behavior in adolescence is a predictor of violence in later age. Risk
      factors for violent behavior could be categorized as individual and
      environmental. Environmental risk factors can be familial, social, and chemical
      environmental. Maltreatment in childhood is an important predictor of violent
      behavior in later age. The presence of mental illness is another important
      predictor of violence. Contemporary television has a visual and auditory power to
      promote violence with all its elements. Computers are another field where
      children confront violence. For identification of individuals who have an
      increased propensity or susceptibility, for violent behavior, research has
      suggested that polymorphisms related to certain genes might be important.
      However, we should emphasize that the expression of such behavior would always
      depend on interactions between various genes, environmental factors, and genetic
      environmental interactions. Experiments in rhesus monkeys have shown that optimal
      early social experiences might overcome the deleterious effects of susceptible
      alleles. The effective prevention of violence should consist of interventions
      that aim to reduce the number of risk factors during early childhood, such as
      home visitation programs and giving individuals the skills and opportunities for
      engaging in positive behaviors during school years and adolescence, coupled with
      the identification of new barriers and reassessment of needs.

PMID- 18348414
TI  - Adolescent reproductive health in Uganda: issues related to access and quality of
      care.
AB  - Adolescent health in Kabarole district, Uganda, is seriously jeopardized by both
      high teenage pregnancy rates and high rates of sexually transmitted diseases,
      including HIV infection. OBJECTIVES: To elucidate views, perceptions and
      attitudes of key informants who are involved in the delivery of reproductive
      health services to adolescents. STUDY GROUP: Four managers of youth-related
      nongovernmental organizations, two government nurses, and four youth leaders.
      METHODS: Qualitative study with content analysis using in-depth interviews.
      RESULTS: Participants agreed that reproductive health services in Kabarole
      district are not adolescent friendly. Most often, lack of privacy and
      confidentiality for the adolescents attending a health unit was cited as one
      important reason. Other factors contributing to a less adolescent friendly
      service environment were inconvenience of services including the fragmentation of
      different service components and lack of specific traIning for health workers on
      how to relate appropriately to adolescents. Also noted was that several
      participants had a negative attitude toward the sexual activity of adolescents.
      Suggestions for service improvement were limited to training of health workers
      and increased support for the infrastructure. CONCLUSIONS: Reproductive health
      services for adolescents in Kabarole district could be strengthened by improving
      the privacy and confidentiality of services. Health workers must also be trained
      in counseling and in treating adolescents in a youth-appropriate and high quality
      fashion. Staff attitudes must also be addressed.

PMID- 18348415
TI  - Hemoglobin status of non-school going adolescent girls in three districts of
      Orissa, India.
AB  - Anemia is a major public health problem in young children and pregnant women in
      SouthEast Asia, but a paucity of data on anemia in adolescent girls in India.
      Studies are lacking on the entire non-school going adolescent population.
      OBJECTIVE: To determine the prevalence of anemia in non-school going adolescent
      girls and the association between hemoglobin (Hb) concentration and socioeconomic
      and nutritional factors. STUDY GROUP: A cross-sectional community study conducted
      on a sample of 1937 healthy adolescent girls aged 11-19 years from three
      districts of Orissa, India. METHODS: Sample size was determined using a
      probability proportionate to size cluster sampling. The adolescent girls were
      interviewed and anthropometric measurements were collected. The Hb estimation was
      carried out in capillary blood samples using the cyanmethemoglobin method. Anemia
      and nutritional status were evaluated according to standard procedures. RESULTS:
      The mean Hb concentration was 9.7 +/- 1.4 g/dL (range, 4.5-13.4 g/dL). Of the
      total adolescent girls, 1869 (96.5%) were anemic (Hb < 12.0 g/dL), of which,
      45.2%, 46.9% and 4.4% had mild, moderate, and severe anemia, respectively. A
      significant curvilinear relation was found between Hb concentration and age, with
      the nadir of the curve occurring in the 12-14 years age group. Girls from Bargarh
      district had significantly lower mean Hb levels than those from the Jajpur and
      Khurda districts. Significant positive associations were found between Hb
      concentration and pre-menarche, community, education levels of girls and their
      parents' family income, body mass index, and mid-upper arm circumference. This
      study revealed that prevalence of anemia was extremely high in non-school going
      adolescent girls (most were moderately anemic) and stressed the need for more
      research and public health interventions.

PMID- 18348416
TI  - Prevalence and risk factors of facial acne vulgaris among Chinese adolescents.
AB  - Acne vulgaris, a very common condition among adolescents, can result in
      psychological distress, including anxiety and depression. The purpose of this
      study was to assess the prevalence and risk factors of acne vulgaris among
      Chinese adolescents. In the Zhou Hai district of Guangdong Province, 3163
      students 10 to 18 years old were selected from 7 schools. Information was
      collected using self-administrated questionnaIres and physician examinations. The
      prevalence of acne vulgaris was calculated from the collected data. Potential
      risk factors including age, gender, diet, skin type, sleeping habits, and facial
      make-up use were analyzed using stepwise logistic regression. The results showed
      a prevalence of acne vuglaris of 53.5% in all adolescents, with 51.3% in males
      and 58.6% in females. The prevalence of inflammatory acne in males and females
      combined was 25.8% and of acne scarring 7.1%. Increased age was related to higher
      prevalence and severity of acne vulgaris: 15.6%, 44.9%, and 70.4% for 10, 13, and
      16 year olds, respectively. Acne vulgaris was more prevalent in girls under and
      boys over 14 years of age. Significant risk factors of acne vuglaris included
      age, skin type (oily, mixed, or neutral skin in comparison with dry skin),
      insufficient sleep, and cosmetic make-up use. CONCLUSION: Acne vulgaris is
      prevalent among Chinese adolescents 10 to 18 years old. Health education to
      address this condition in Chinese adolescents could have important implications
      for public health.

PMID- 18348417
TI  - Health-related profiles of study delay in university students in The Netherlands.
AB  - Compared with their working peers, students report more health complaints. A
      worse self-rated health status could hinder students to function optimally within
      the high demands of studying at university. On the other hand, it can be expected
      that worse academic functioning may have a negative influence on existing health
      problems or even initiate health problems. The aim of this study was to
      investigate associations between indicators of health and study delay in
      university students in the Netherlands. A group of 5,859 students was invited to
      complete a questionnaire, consisting of questions about general health, fatigue,
      psychological health, support, study-related issues, study-related problem
      solving, time pressure, perceived study delay and program study delay. Three
      study delay profiles were calculated--program delay without perceived delay (A),
      perceived delay without program delay (B), and perceived and program delay (C)
      with no study delay as reference. The response rate was 51%. Profile A was
      associated with unfavorable outcomes in support, study-related issues, and study
      related problem solving. Profiles B and C presented unfavorable outcomes in all
      dimensions. Perceived study delay appeared to be a more important determinant of
      unfavorable outcomes than program delay. The group with perceived delay without
      program delay closely resembled the group with perceived and program delay. This
      group may be at risk for future program-study delay.

PMID- 18348418
TI  - Knowledge, attitudes and perceptions of the teacher's role in sexuality education
      in public schools in Nigeria.
AB  - The purpose of this study was to describe the knowledge, attitude, and perception
      of teachers of their role in the sexuality education of secondary school students
      with a viewto suggesting strategies for improvement. METHODS: The study was a
      descriptive cross-sectional survey. Information was collected from 305 secondary
      school teachers selected by multi-stage random sampling method from Osun state,
      Nigeria using a pre-tested semi-structured questionnaire. RESULTS: Median age of
      respondents was 36 +/- 8.18 years. Male/female ratio was 1:1.2. Knowledge about
      key reproductive issues was poor and inadequate. Knowledge of more than one
      contraceptive method was low (39.0%), Condom was the most frequently mentioned
      (59.3%). The teachers exhibited poor perception of their role in sexuality
      education of their students. 52.8% placed the sole responsibility for sexuality
      education on parents and only 20.7% found that it should start before age 10
      years. Mean menarcheal age was 13.1 +/- 1.7 y. A statistically significant
      association was found between respondents' gender and knowledge of menarcheal age
      (p = .03); and between class taught and knowledge of menarcheal age (p = .003).
      86.90% had positive attitude towards inclusion of sexuality education in the
      school curriculum; however, 43.6% felt that contraceptive methods should not be
      part of the course content. CONCLUSION: An urgent need exists for education and
      re-orientation of teachers through seminars and workshops, in-service training
      education program to equip them properly for the task. Policy makers need to
      formulate a definite, explicit, and workable sexuality education policy.

PMID- 18348419
TI  - Young adults' judgments of the costs and benefits of smoking: The predictive
      efficacy of different outcome weightings in behavioral decision making.
AB  - Given the public health burden of smoking and the knowledge that many smokers
      begin during adolescence and young adulthood, understanding how decisions about
      smoking behaviors are made is of considerable importance. Most health decision
      making models relevant to understandingbenefits smoking behavior posit that
      beliefs about the costs and of smoking are an important influence on decision
      making. However, these models differ in how other factors (e.g., outcome
      importance, perceived positivity or negativity of outcome) are weighted in cost
      benefit analyses. We examined the relative efficacy of different weightings in
      cost/benefit formulations to predict young adults' current smoking behavior and
      intentions to smoke in the future. Smoking and non-smoking participants listed
      advantages and disadvantages of smoking and then rated the importance and
      positivity/negativity of each outcome. Number of consequences listed,
      consequences weighted by importance, by positivity/negativity, and by an
      importance, x positivity/negativity interaction were examined as predictors of
      both current smoking status and reported intentions to smoke in 5 years. Both
      importance and positivity/negativity (but not their interaction) predicted
      current smoking status, whereas importance alone was the strongest predictor of
      future smoking intentions. This suggests the possibility that different decision
      making processes might underlie future behavioral intentions relative to those
      that guide current behavior.

PMID- 18348420
TI  - Age-related gender differences of relevance for health in Swedish adolescents.
AB  - AIM: To compare different areas of adolescent behaviors and self-perceived health
      with the aim of identify'ing age and gender differences to facilitate planning of
      public health preventive measures. METHODS: A cross-sectional survey in ten
      Swedish schools covering all students between 13 and 18 years of age. A validated
      instrument, Q90, created for use in teenagers, was distributed in the classrooms
      to 3,216 teenagers. RESULTS: In all age groups, girls had significantly more
      problems regarding self-perceived health, i.e., general health, abdominal pain,
      headache, feeling depressed, and suicidal thoughts, than boys. Ingirls,
      proportion feelingdepressed increased from 28% inthe youngest group (11% in boys)
      to 51% in the oldest (20% in boys). Similar results were found for all health
      related problems. Significant differences were found between both gender and age
      groups in experiences of being bullied. A significantly higher frequency of boys
      than girls admitted to committing vandalism (35% vs. 11% in the oldest age
      group). The frequency of girls feeling overweight increased moderately with age,
      from 35% at age 13 y to 50% at age 18 y. The proportion of boys feeling
      underweight increased more distinctly, from 8% at age 13 y to 29% at age 18 y.
      Tobacco use and alcohol habits were similar in gender comparisons. CONCLUSION:
      The study demonstrates areas of normative development from early to late
      adolescence. The striking differences in health perception between girls and boys
      must be stressed. The results might form a basis for teachers, school health
      workers, and other health authorities working with adolescents.

PMID- 18348421
TI  - Health, health-compromising behavior, risk-taking behavior and sexuality in
      female and male high school students in vocational compared with theoretical
      programs in Sweden.
AB  - The aim of the present study was to determine whether adolescents attending
      vocational high school programs in Sweden show unhealthy or risky behaviors to a
      higher extent than those attending theoretical programs, and whether there were
      gender differences. METHODS: All eligible adolescents 16-18 years old, after
      exclusion of first- and second-generation immigrants, attending high school
      (1,332 pupils) in a medium-sized town in Sweden completed a validated in-depth
      questionnaire (Q90) with 165 questions in the classroom. In comparisons,
      adjustments were made for socio-demographic variables. RESULTS: A significant
      difference was found for the variable having at least one parent with university
      education (odds ratio (OR 0.28) for those attending vocational programs). In
      girls: have bullied (OR 2.01), eat breakfast all school days (OR 0.31), have
      shoplifted (OR 3.46), smoking (OR 5.69), and have had more than five sexual
      partners (OR 4.74) all differed significantly. Some variables with significant
      differences in boys were; eat fruit or vegetables every day (OR 0.55), feeling
      depressed (OR 0.62), sports activity at least once a week (OR 0.56), vandalizing
      (OR 2.11), regular alcohol use (OR 1.44), and contraceptive use at latest sexual
      intercourse (OR 0.47). CONCLUSIONS: The findings suggest that preventive
      interventional strategies, aimed at improving health maintenance among
      adolescents should take into consideration the differences between students in
      vocational and theoretical programs, including the cluster and accumulation of
      health-risk behaviors.

PMID- 18348422
TI  - Youth at risk: identifying correlates of violence in Bolivia.
AB  - BACKGROUND: Although violence is one of the leading causes of mortality
      worldwide, in Latin America the prevalence of violence and factors associated
      with violent behavior among youth are largely unknown. OBJECTIVE: We describe the
      prevalence of carrying a weapon among Bolivian adolescent males and identify risk
      factors associated with weapon carrying. METHODS: The Youth Risk Behavior Survey
      was administered to a sample of teenagers 13-18 years of age (394 males and 182
      females) from randomly selected schools in La Paz, Bolivia. The study is limited
      to males because of the small sample size for females. Frequencies and chi-square
      tests were calculated and logistic regression was used to identify factors
      associated with carrying a weapon in the past 30 days. RESULTS: Among the sample
      population, one-quarter of adolescent boys reported carrying a weapon in the
      previous 30 days. Ever having used cigarettes was the risk factor most strongly
      associated with weapon carrying. Additional risk factors included having
      participated in a physical fight, having used cocaine, and sniffing glue or other
      inhalants. CONCLUSION: Our results showed a link between weapon carrying and
      other risk behaviors, including smoking, drug use and fighting. Understanding the
      factors associated with carrying weapons among youth is an essential step in
      determining which risk behaviors should be included in comprehensive programs
      focused on youth violence prevention.

PMID- 18348423
TI  - Measures of resilience and adaptation of adolescents in single parent families in
      Taiwan: psychometric properties and related profiles.
AB  - The dimensionality of measures of resilience (74 items) and adaptation (35 items)
      were examined in 291 adolescents living in single parent families in Taiwan.
      Factor analyses showed that internally consistent factors with high loadings
      could be derived from: (a) resilience items with reference to different
      ecological systems, including personal domain (six factors), family domain (eight
      domains), school domain (three domains), and community domain (three domains);
      and (b) adaptation problem items (eight factors). An examination of the profile
      of responses of the respondents showed that several concerns in the areas of
      resilience (effective coping, parental protection from being hurt by parental
      divorce, home-school cooperation, and connection with outside resources) and
      adaptation (problems in academic aspirations, low self-regard, and low self
      control) were identified.

PMID- 18348424
TI  - Endothelial function analysis and atherosclerotic risk factors in adolescents
      with systemic lupus erythematosus.
AB  - Atherosclerosis is considered an important cause of morbidity and mortality in
      systemic lupus erythematosus (SLE). Endothelial dysfunction represents an
      important factor in the onset of atherosclerosis. OBJECTIVE: To assess
      endothelial function and the risk factors for atherosclerosis in adolescents with
      SLE. SUBJECTS: Thirty-five adolescents with SLE aged between 10-18 years and 27
      age- and sex-matched controls. METHODS: Endothelial function was assessed using a
      high-resolution ultrasound device (Philips ATL, HDI-3000 model) with a linear
      array transducer (4.0-7.0 MHz). Measures of diameter and flow were performed at
      rest, during reactive hyperemia and after glyceryl trinitrate. Total cholesterol
      and fractions, triglycerides, creatinine, fasting glucose, anticardiolipin
      antibodies, lupus anticoagulant and plasma homocysteine, as well as, cumulative
      oral corticoid dose were considered in order to establish the risk factors for
      atherosclerosis. RESULTS: No significant difference was found between the two
      groups regarding endothelial function. Although dilation at 90" after cuff
      deflation had been smaller in patients than in controls, the difference was not
      statistically significant. Patients had higher levels of total cholesterol (p =
      0.02), VLDL (p = 0.01), triglycerides (p = 0.01), and homocysteine (p < .001)
      compared with controls. Sixty eight percent of our patients showed
      hyperhomocysteinemia, yet, we did not find any correlation between these values
      and flow-mediated dilation. CONCLUSION: According to our results, adolescents
      with SLE do not present alterations in endothelial function as assessed by
      ultrasound. However, these patients did demonstrate risk factors such as
      dyslipidemia and hyperhomocysteinemia for the development of atherosclerosis.

PMID- 18348425
TI  - A pilot study on religiousness/spirituality and ADHD.
AB  - BACKGROUND: The phenomena of religiousness and spirituality bear on issues of
      personal behavioral control and interpersonal relationships. Behavioral control
      and social relationships can be affected by attention deficit/hyperactivity
      disorder (ADHD). AIM: The object ofthis pilot study was to explore possible
      connections between religiousness/spirituality and the clinical diagnosis ADHD. A
      group of adolescent psychiatric outpatients (n=117) completed the Brief
      Multidimensional Measure of Religiousness/Spirituality. Clinical diagnosis was
      obtained from the clinic chart. RESULTS: Logistic regression modeling revealed no
      significant relation between the various dimensions of religiousness/spirituality
      and diagnosis of ADHD. CONCLUSIONS: The findings presented here are in need of
      replication but could add to clinical understanding of ADHD.

PMID- 18348426
TI  - Level of religiosity and disordered eating psychopathology among modern-orthodox
      Jewish adolescent girls in Israel.
AB  - OBJECTIVE: To examine the relation between level of religiosity, grade level,
      self-esteem, and level of disordered eating-related psychopathology among Modem
      Orthodox Jewish adolescent girls in Israel. METHOD: The sample consisted of 320
      Jewish religious adolescent schoolgirls in the 9th to 12th grades of middle and
      high schools. The girls completed the Eating Disorder Inventory-2 (EDI-2) and the
      religious questionnaire based on Guttman's instrument. RESULTS: The more
      religious the student, the less eating-related psychopathology was found. The
      youngest students (grade 9) were found to be the least religious and to have the
      highest eating-related psychopathology. DISCUSSION: The results are discussed in
      terms of the possibility that level of religiosity might to some extent protect
      adolescent girls against developing body dissatisfaction and disordered eating
      pathology. A high level of religiosity is associated with less emphasis on the
      physical attractiveness of women and less pressure for their success and
      achievement outside the home.

PMID- 18348427
TI  - Social support and loneliness in college students: effects on pulse pressure
      reactivity to acute stress.
AB  - Socially supportive relationships at university may buffer against psychological
      stress in students, particularly in those experiencing loneliness. OBJECTIVES: To
      examine the relation of social support at university and loneliness with pulse
      pressure (PP) reactivity to acute psychological stress in a sample of first-year
      undergraduate students. STUDY GROUP: Sixty-five female, adolescent, first-year
      university students. METHODS: Pulse pressure (PP) was calculated as the
      arithmetic difference between systolic blood pressure and diastolic blood
      pressure, which were measured during a resting baseline and during a stressful
      reading task. The difference between baseline and reading task PP represents PP
      reactivity. The Social Support at University Scale (SSUS) was used to assess
      social support availability in university, and the Revised UCLA Loneliness Scale
      was used to assess loneliness. Hierarchical linear regression was used to examine
      main and interactive effects of SSUS and loneliness on PP change scores, and
      simple slopes were computed to assist in the interpretation of interaction
      effects. RESULTS: Social support at university was associated with lower PP
      reactivity in students reporting medium (t = -2.03, p = .04) or high levels of
      loneliness (t = -2.93, p = .004), but not in those reporting low levels of
      loneliness (t = -0.20, p = .83). CONCLUSIONS: Psychosocial interventions designed
      to increase social support available at university, and targeted at students
      experiencing loneliness may buffer against the harmful effects of acute stressors
      in lonely first-year students.

PMID- 18348428
TI  - Parental behavioral control in academic and non-academic domains: a three-year
      longitudinal study in the Chinese culture.
AB  - For over three consecutive years, 2559 Chinese adolescents (mean age = 12.65
      years at Wave 1) responded to instruments assessing their perceived parental
      behavioral control based on measures of parental knowledge, expectation,
      monitoring, and discipline. The results show that compared with parental control
      in the academic domain, parental control in the non-academic domain (peer
      relations domain) was relatively weaker, using parental knowledge, parental
      expectation, parental monitoring, and parental discipline as indicators, and a
      decline in parental behavioral control occurred over time. Although domain
      (academic domain versus non-academic domain) X time (Time 1, Time 2 versus Time
      3) interaction effects were found, the findings mirrored the main effects of
      domain and time. Parental education and economic sufficiency were linearly
      related to differences in parental behavioral control in the academic domain and
      non-academic domain. The present findings suggest that traditional Chinese
      cultural emphasis on academic excellence still prevails in the contemporary
      Chinese culture.

PMID- 18348429
TI  - Qualitative research in psychology: Could William James get a job?
AB  - Considering the case of William James, the author examines the likelihood of a
      successful career as a qualitative researcher in contemporary U.S. psychology.
      Fifty-seven journals affiliated with the American Psychological Association or
      its divisions were analyzed to show the place of qualitative research in U.S.
      psychology over the past 50 years. Journal abstracts, mission statements, and a
      short e-mail questionnaire from editors were used to understand patterns and
      trends in qualitative research in U.S. psychology. Editors are generally
      accepting of qualitative work, although mission statements do not always signal
      likely interest in qualitative work. The amount of qualitative work published is
      comparably low, but patterns of increased publication are found in some journals.
      Trends in methodologies, topics of research, and ways in which qualitative
      research enters journals over time are discussed. Suggestions for the publication
      of qualitative work are provided.

PMID- 18348431
TI  - Diverse and dynamic medical device technology industry.

PMID- 18348430
TI  - Curt Richter: psychobiology and the concept of instinct.
AB  - Curt Richter is at the origins of psychobiology in the United States. For Richter
      the concept of instinct was central to his research. While he had diverse
      interests that traversed a great range of psychobiology, the concept of instinct
      was fundamental to his research on specific hungers and the regulation of the
      internal milieu. Debates about the concept of instinct would last the bulk of
      Richter's experimental career, culminating in an international conference a
      decade after the Second World War.

PMID- 18348432
TI  - Polyetheretherketone for long-term implantable devices.
AB  - Extremely few new polymeric materials become adopted by the medical device
      industry. This is partly because of the quality of existing materials and partly
      a consequence of the high costs of introducing new ones. The
      polyaryletherketones, especially polyetheretherketone (PEEK) has broken this
      trend and is rapidly emerging as a contender for high performance implantable
      applications.

PMID- 18348433
TI  - The evolving functionalities of coating.
AB  - Coatings that mediate the interface between biological tissue and implant are
      arguably some of the most critical material components that affect the
      performance of a medical device. Developments in coatings for catheters and
      stents are reviewed here and include biodegradable and cell signalling coatings
      that are currently in clinical trials.

PMID- 18348434
TI  - A hydrophilic technology for intermittent urinary catheters.
AB  - A biocompatible and highly lubricous hydrophilic coating has been developed for
      intermittent urinary catheters. The coating has additives incorporated into it,
      which reduce the drying out of the catheter when it is inserted into the urethra,
      and antimicrobial agents can be incorporated into it to minimise the trauma
      associated with catheterisation.

PMID- 18348435
TI  - Predictive modelling for delivery shaft design.

PMID- 18348436
TI  - The use of adhesives for catheter bonding.
AB  - This article discusses the selection of adhesives for catheter bonding and
      provides insights into joint design, adhesive curing, and dispensing techniques.

PMID- 18348437
TI  - Scope of the European Medical Device Directives.
AB  - Can a product that incorporates nonviable human tissue be regulated as a medical
      device in Europe? Is a product that includes viable tissues or cells of animal
      origin regulated as a medical device? Is a product that incorporates a human
      blood derivative regulated as a medical device? This article discusses the scope
      of the medical device Directives and the regulatory status of products that are
      excluded.

PMID- 18348438
TI  - Optimised system configuration for stent manufacturing.
AB  - Optimising the major components of a laser stent machining platform will lead to
      improved part quality and machine throughput. Mechanical, control and software
      elements are reviewed here. Trends in stent design are also discussed together
      with their implications on these machine design elements.

PMID- 18348439
TI  - Silicones in medical electronics.
AB  - The use of silicones, although already extensive, is set to grow in medical
      electronics. Silicones used in medical device applications as tubing or moulded
      parts should also be considered for electronic applications in the same device.
      This article outlines the potential reduction in complexity that this solution
      offers. Benefits include eliminating negative materials interactions and avoiding
      bonding problems.

PMID- 18348440
TI  - Developments in functional electrical stimulation systems.
AB  - It is estimated that more than 750,000 people suffer a stroke each year in
      Europe. An implantable neurostimulator is being developed to improve impaired
      upper limb function that results from stroke. Its mode of operation and early
      clinical trial results are reported.

PMID- 18348441
TI  - Nanomedicine: rethinking medical training.
AB  - A change in perspective and an expansion in knowledge are required if society is
      to benefit from nanomedical products. As more products become a reality, the
      current concept of "disease" may be set to undergo a paradigm shift.

PMID- 18348442
TI  - Switzerland: the pragmatics of business.
AB  - Switzerland has a population of seven million and approximately 600 medical
      technology companies are located there. This equates to one company per 12
      thousand people and arguably the highest density in the world. The factors that
      make the country a successful place to do business are outlined in this interview
      with Professor Bestetti, Head of the CTI Medtech initiative.

PMID- 18348443
TI  - Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need?
AB  - Vtamin D is the sunshine vitamin for good reason. During exposure to sunlight,
      the utraviolet B photons enter the skin and photolyze 7-dehydrocholesterol to
      previtamin D3 which in turn is isomerized by the body's temperature to vitamin
      D3. Most humans have depended on sun for their vitamin D requirement. Skin
      pigment, sunscreen use, aging, time of day, season and latitude dramatically
      affect previtamin D3 synthesis. Vitamin D deficiency was thought to have been
      conquered, but it is now recognized that more than 50% of the world's population
      is at risk for vitamin D deficiency. This deficiency is in part due to the
      inadequate fortification of foods with vitamin D and the misconception that a
      healthy diet contains an adequate amount of vitamin D. Vitamin D deficiency
      causes growth retardation and rickets in children and will precipitate and
      exacerbate osteopenia, osteoporosis and increase risk of fracture in adults. The
      vitamin D deficiency has been associated pandemic with other serious consequences
      including increased risk of common cancers, autoimmune diseases, infectious
      diseases and cardiovascular disease. There needs to be a renewed appreciation of
      the beneficial effect of moderate sunlight for providing all humans with their
      vitamin D requirement for health.

PMID- 18348444
TI  - Solar ultraviolet irradiance and cancer incidence and mortality.
AB  - Evidence supporting the UVB/vitamin D/cancer theory continues to mount with
      little detraction, although there are some inconsistent results, such as some
      from Nordic countries, with respect to serum calcidiol levels. Also, studies
      designed and conducted before it was realized that dietary sources are largely
      inadequate to have a pronounced effect on cancer risk were largely unable to
      confirm a beneficial role for vitamin D in reducing the risk of cancer. The
      analysis of the economic burden of solar UVB irradiance and vitamin D
      deficiencies compared to excess solar UV irradiance for the United States yielded
      interesting findings. One was that the US economic burden due to vitamin D
      insufficiency from inadequate exposure to solar UVB irradiance, diet and
      supplements was estimated at $40 billion to $56 billion in 2004, whereas the
      economic burden for excess UV irradiance was estimated at $6 billion to $7
      billion. These findings are probably still approximately correct, if not on the
      low side, with respect to vitamin D because of the additional benefits found
      recently, such as protection against infectious diseases.

PMID- 18348445
TI  - Vitamin D status and cancer incidence and mortality.

PMID- 18348446
TI  - Sun exposure and cancer survival in Norway: changes in the risk of death with
      season of diagnosis and latitude.
AB  - Epidemiological and experimental studies suggest that derivatives of vitamin D
      may improve prognosis of a number of cancer types. Sun is our most important
      source of vitamin D. Seasonal variations and latitudinal gradients of calcidiol
      (the marker of vitamin D status) have been reported. We wanted to investigate if
      season and latitude play any role for survival from seven different cancer types
      in Norway. Seasonal and geographical variations of vitamin D were estimated by
      calculations and were compared with clinical data. For the survival analyses,
      249373 cancer patients were followed for three years after diagnosis and the risk
      of death was analyzed separately for summer- and winter diagnosis, as well as for
      two geographical regions with different UV exposures. We found a 15-25% better
      survival for patients diagnosed during summer and a slight beneficial effect for
      residents of the high UV region for some of the cancer forms investigated. Based
      on our results we suggest that calcidiol concentration at the time of cancer
      diagnosis is related to survival and discuss briefly ways to improve the vitamin
      D levels in the general population.

PMID- 18348447
TI  - Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes.
AB  - Recent evidence suggests that higher vitamin D intakes beyond current
      recommendations may be associated with better health outcomes. In this chapter,
      evidence is summarized from different studies that evaluate threshold levels for
      serum 25(OH)D levels in relation to bone mineral density (BMD), lower extremity
      function, dental health, risk of falls, admission to nursing home, fractures,
      cancer prevention and incident hypertension. For all endpoints, the most
      advantageous serum levels for 25(OH)D appeared to be at least 75 nmol/l (30
      ng/ml) and for cancer prevention, desirable 25(OH)D levels are between 90-120
      nmol/l (36-48 ng/ml). An intake of no less than 1000 IU (25 mcg) of vitamin D3
      (cholecalciferol) per day for all adults may bring at least 50% of the population
      up to 75 nmol/l. Thus, higher doses of vitamin D are needed to bring most
      individuals into the desired range. While estimates suggest that 2000 IU vitamin
      D3 per day may successfully and safely achieve this goal, the implications of
      2000 IU or higher doses for the total adult population need to be addressed in
      future studies.

PMID- 18348448
TI  - Ultraviolet exposure scenarios: risks of erythema from recommendations on
      cutaneous vitamin D synthesis.
AB  - Exposure to sunlight is a major source of vitamin D for most people yet public
      health advice focuses overwhelmingly on avoiding exposure of unprotected skin
      because of the risks of erythema and skin cancer. We have calculated the exposure
      required to gain a number of proposed oral-equivalent doses of vitamin D, as
      functions of latitude, season, skin type and skin area exposed, together with the
      associated risk of erythema, expressed in minimum erythema doses. The model
      results show that the current recommended daily intake of 400 IU is readily
      achievable through casual sun exposure in the midday lunch hour, with no risk of
      erythema, for all latitudes some of the year and for all the year at some (low)
      latitudes. At the higher proposed vitamin D dose of 1000 IU lunchtime sun
      exposure is still a viable route to the vitamin, but requires the commitment to
      expose greater areas of skin, or is effective for a shorter period of the year.
      The highest vitamin D requirement considered was 4000 IU per day. For much of the
      globe and much of the year, this is not achievable in a lunchtime hour and where
      it is possible large areas of skin must be exposed to prevent erythema. When the
      only variable considered was skin type, latitudinal and seasonal limits on
      adequate vitamin D production were more restrictive for skin type 5 than skin
      type 2.

PMID- 18348449
TI  - At what time should one go out in the sun?
AB  - To get an optimal vitamin D supplement from the sun at a minimal risk of getting
      cutaneous malignant melanoma (CMM), the best time of sun exposure is noon. Thus,
      common health recommendations given by authorities in many countries, that sun
      exposure should be avoided for three to five hours around noon and postponed to
      the afternoon, may be wrong and may even promote CMM. The reasons for this are
      (1) The action spectrum for CMM is likely to be centered at longer wavelengths
      (UVA, ultraviolet A, 320-400 nm) than that of vitamin D generation (UVB,
      ultraviolet B, 280-320 nm). (2) Scattering of solar radiation on clear days is
      caused by small scattering elements, Rayleigh dominated and increases with
      decreasing wavelengths. A larger fraction of UVA than of UVB comes directly and
      unscattered from the sun. (3) The human body can be more realistically
      represented by a vertical cylinder than by a horizontal, planar surface, as done
      in almost all calculations in the literature. With the cylinder model, high UVA
      fluence rates last about twice as long after noon as high UVB fluence rates do.
      In view of this, short, nonerythemogenic exposures around noon should be
      recommended rather than longer nonerythemogenic exposures in the afternoon. This
      would give a maximal yield of vitamin D at a minimal CMM risk.

PMID- 18348450
TI  - Epidemiology of melanoma and nonmelanoma skin cancer--the role of sunlight.
AB  - Melanoma and nonmelanoma skin cancer (NMSC) are now the most common types of
      cancer in white populations. Both tumor entities show an increasing incidence
      rate worldwide but a stable or decreasing mortality rate. The rising incidence
      rates of NMSC are probably caused by a combination of increased sun exposure or
      exposure to ultraviolet (UV) light, increased outdoor activities, changes in
      clothing style, increased longevity, ozone depletion, genetics and in some cases,
      immune suppression. A dose-dependent increase in the risk of squamous cell
      carcinoma (SCC) of the skin was found associated with exposure to Psoralen and
      UVA irradiation. An intensive UV exposure in childhood and adolescence was
      causative for the development of basal cell carcinoma (BCC) whereas for the
      aetiology of SCC a chronic UV exposure in the earlier decades was accused.
      Cutaneous malignant melanoma is the most rapidly increasing cancer in white
      populations. The frequency of its occurrence is closely associated with the
      constitutive colour of the skin and depends on the geographical zone. The highest
      incidence rates have been reported from Queensland, Australia with 56 new cases
      per year per 100,000 for men and 43 for women. Mortality rates of melanoma show a
      stabilisation in the USA, Australia and also in European countries. The tumor
      thickness is the most important prognostic factor in primary melanoma. There is
      an ongoing trend towards thin melanoma since the last two decades.
      Epidemiological studies have confirmed the hypothesis that the majority of all
      melanoma cases are caused, at least in part, by excessive exposure to sunlight.
      In contrast to squamous cell carcinoma, melanoma risk seems not to be associated
      with cumulative, but intermittent exposure to sunlight. Therefore campaigns for
      prevention and early detection are necessary.

PMID- 18348451
TI  - Ultraviolet radiation and malignant melanoma.
AB  - Essential features of the epidemiology and photobiology of cutaneous malignant
      melanoma (CMM) in Norway were studied in comparison with data from countries at
      lower latitudes. Arguments for and against a relationship between ultraviolet
      radiation (UV) from sun and sun beds are discussed. Our data indicate that UV is
      a carcinogen for CMM and that intermittent exposures are notably melanomagenic.
      This hypothesis was supported both by latitude gradients, by time trends and by
      changing patterns of tumor density on different body localizations. However, even
      though UV radiation generates CMM, it may also have a protective action and/or an
      action that improves prognosis. The same may be true for a number of internal
      cancers. There appears to be no, or even an inverse latitude gradient for CMM
      arising on non-UV exposed body localizations (uveal melanoma). Furthermore, CMM
      prognosis was gradually improved over all years of increasing incidence (up to
      1990), but during the last 10 to 15 years, incidence rates decreased and
      prognosis was not further improved. While CMM incidence rates are twice as high
      in South Norway as in North Norway, the ratios of death rates to incidence rates
      are higher in the North, where the annual UV fluences are lower. Death- and
      incidence rates in Australia and New Zealand fully support this. Comparisons of
      skin cancer data from Norway and Australia/New Zealand indicate that squamous
      cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB
      fluences, while UVA fluences play a larger role for CMM.

PMID- 18348452
TI  - Solar UV exposure and mortality from skin tumors.
AB  - Solar ultraviolet radiation (UVR) exposure is clearly associated with increased
      mortality from nonmelanoma skin cancer--usually squamous cell carcinoma. However,
      the association with cutaneous melanoma is unclear from the evidence in ecologic
      studies and the few analytic studies show that high levels of intermittent UV
      exposure prior to diagnosis are somehow associated with improved survival from
      melanoma. Understanding this conundrum is critical to present coherent public
      health messages and to improve the mortality rates from melanoma.

PMID- 18348453
TI  - Health initiatives for the prevention of skin cancer.

PMID- 18348454
TI  - Sunscreens.

PMID- 18348455
TI  - UV damage and DNA repair in malignant melanoma and nonmelanoma skin cancer.
AB  - Exposition of the skin with solar ultraviolet radiation (UV) is the main cause of
      skin cancer development. The consistently increasing incidences of melanocytic
      and nonmelanocytic skin tumors are believed to be at least in part associated
      with recreational sun exposure. Epidemiological data indicate that excessive or
      cumulative sunlight exposition takes place years and decades before the resulting
      malignancies arise. The most important defense mechanisms that protect human skin
      against UV radiation involve melanin synthesis and active repair mechanisms. DNA
      is the major target of direct or indirect UV-induced cellular damage. Low
      pigmentation capacity in white Caucasians and rare congenital defects in DNA
      repair are mainly responsible for protection failures. The important function of
      nucleotide excision DNA repair (NER) to protect against skin cancer becomes
      obvious by the rare genetic disease xeroderma pigmentosum, in which diverse NER
      genes are mutated. In animal models, it has been demonstrated that UVB is more
      effective to induce skin cancer than UVA. UV-induced DNA photoproducts are able
      to cause specific mutations (UV-signature) in susceptible genes for squamous cell
      carcinoma (SCC) and basal cell carcinoma (BCC). In SCC development, UV-signature
      mutations in the p513 tumor suppressor gene are the most common event, as
      precancerous lesions reveal approximately 80% and SCCs > 90% UV-specific p53
      mutations. Mutations in Hedgehog pathway related genes, especially PTCH1, are
      well known to represent the most significant pathogenic event in BCC. However,
      specific UV-induced mutations can be found only in approximately 50% of sporadic
      BCCs. Thus, cumulative UVB radiation can not be considered to be the single
      etiologic risk factor for BCC development. During the last decades, experimental
      animal models, including genetically engineered mice, the Xiphophorus hybrid
      fish, the south american oppossum and human skin xenografts, have further
      elucidated the important role of the DNA repair system in the multi-step process
      of UV-induced melanomagenesis. An increasing body of evidence now indicates that
      nucleotide excision repair is not the only DNA repair pathway that is involved in
      UV-induced tumorigenesis of melanoma and nonmelanoma skin cancer. An interesting
      new perspective in DNA damage and repair research lies in the participation of
      mammalian mismatch repair (MMR) in UV damage correction. As MMR enzyme hMSH2
      displays a p53 target gene, is induced by UVB radiation and is involved in NER
      pathways, studies have now been initiated to elucidate the physiological and
      pathophysiological role of MMR in malignant melanoma and nonmelanoma skin cancer
      development.

PMID- 18348456
TI  - Role of viruses in the development of squamous cell cancer and melanoma.
AB  - In this chapter, the evidence for the role of human papilloma virus (HPV) in the
      pathogenesis of squamous cell cancer of the skin will be reviewed. Considerable
      dispute exists questioning the etiological role of HPV. This is due to the low
      copy number ofHPV DNA in skin cancers and additional cofactors such as UV
      exposure, immunosuppression, light skin color and hyperproliferative skin disease
      as well as the genetic background of the host. These additional cofactors are
      probably required because of the weak transforming activity of cutaneous HPV
      types in contrast to high-risk genital HPV strains. On a different note, the
      involvement of viruses in the etiology of melanoma has only recently been
      suggested. Melanoma-associated retrovirus (MelARV) has been detected in mice and
      men and was shown to subvert immunosurveillance besides insertional mutagenesis.
      The state of the art of viral participation in melanomagenesis will be discussed.

PMID- 18348457
TI  - Melanoma and nonmelanoma skin cancers and the immune system.

PMID- 18348458
TI  - Solar UV-radiation, vitamin D and skin cancer surveillance in organ transplant
      recipients (OTRs).
AB  - The introduction of organ transplantation in clinical medicine has resulted in a
      constantly increasing, large population of patients that are chronically on
      immunosuppressive medication. It is well known that skin cancer, especially SCC,
      in this population has higher incidence rates, behaves more aggressively and has
      higher rates of metastasis. OTRs who have been treated for many years with
      immunosuppressive medication are at the highest risk for developing malignant
      skin tumors. Therefore, the intensity of surveillance for cutaneous lesions is of
      high importance in OTRs. A full-body skin exam at least once a year and more
      frequently if skin cancer or precancerous cutaneous lesions develop is
      recommended. Clinicians should not hesitate to biopsy or to surgically excise any
      suspicious skin lesion. Of high importance is also the education of OTRs about
      their increased risk. Protection against solar and artificial UV-radiation and
      monthly self-examinations are good ways to prevent and to recognize any new
      suspicious skin lesions. Patients are advised to always wear solar UV-radiation
      protection (e.g., clothing, sunscreen) before going outdoors. However,
      investigations have revealed that solar UV-B-exposure and serum 25(OH)D levels
      positively correlate with decreased risk for various internal malignancies (e.g.,
      breast, colon, prostate and ovarian cancer) and other severe diseases. As we have
      shown previously, renal transplant recipients are at high risk of vitamin D
      deficiency. A sunscreen with a sun protection factor (SPF)-8 reduces the skin's
      production of vitamin D by 95%. Clothing completely blocks all solar UVB
      radiation and this prevents any vitamin D production. Therefore, it is important
      to detect and treat vitamin D deficiency in solid organ transplant recipients.
      Optimal management of these patients requires communication between the
      transplant teams and the treating dermatologist and other clinicians. For
      advanced or metastatic disease, collaboration between clinicians of different
      disciplines, including the transplant team, dermatologists and radiation
      oncologists is also essential. In the future, dermatology clinics that are
      integrated into transplant centers may make it easier to manage and to treat
      OTRs, may make an interdisciplinary approach more effective and may thereby
      improve the clinical outcome in OTRs.

PMID- 18348459
TI  - Histology of melanoma and nonmelanoma skin cancer.

PMID- 18348460
TI  - Cytogenetics of melanoma and nonmelanoma skin cancer.
AB  - Cytogenetic analysis of melanoma and nonmelanoma skin cancers has revealed
      recurrent aberrations, the frequency of which is reflective of malignant
      potential. Highly aberrant karyotypes are seen in melanoma, squamous cell
      carcinoma, solar keratosis and Merkel cell carcinoma with more stable karyotypes
      seen in basal cell carcinoma, keratoacanthoma, Bowen's disease,
      dermatofibrosarcoma protuberans and cutaneous lymphomas. Some aberrations were
      common amongst a number of skin cancer types including rearrangements and
      numerical abnormalities of chromosome 1, -3p, +3q, partial or entire trisomy 6,
      trisomy 7, +8q, -9p, +9q, partial or entire loss of chromosome 10, -17p, +17q and
      partial or entire gain of chromosome 20. Combination of cytogenetic analysis with
      other molecular genetic techniques has enabled the identification of not only
      aberrant chromosomal regions, but also the genes that contribute to a malignant
      phenotype. This review provides a comprehensive summary of the pertinent
      cytogenetic aberrations associated with a variety of melanoma and nonmelanoma
      skin cancers.

PMID- 18348461
TI  - Molecular biology of basal and squamous cell carcinomas.
AB  - Basal cell carcinomas and Squamous cell carcinomas are the two most common human
      cancers. The incidence of these two types of cancer is estimated to double within
      20 years. Identification of the key molecular events is critical in helping us
      design novel strategies to treat and to prevent these cancers. For example,
      identification of hedgehog signaling activation has opened up many opportunities
      for targeted therapy and prevention of basal cell carcinomas. Significant
      progress has also been made in our understanding of squamous cell carcinomas of
      the skin. In this chapter, we will focus on major recent developments in our
      understanding of basal cell carcinomas and squamous cell carcinomas at the
      molecular levels and their clinical implications.

PMID- 18348462
TI  - Molecular biology of malignant melanoma.
AB  - The incidence of melanoma has increased more rapidly than any other type of
      cancer. In this review, we summarize the most important genetic alterations that
      contribute to the development of malignant melanoma. Our knowledge of the genetic
      and biological events involved in the genesis and progression of this disease has
      been benefited from the evolvement of a wealth of genetically engineered animal
      models. Hopefully, the understanding generated by all these studies will
      contribute to develop new therapeutic strategies to handle this fatal malignancy.

PMID- 18348463
TI  - P53 protein and pathogenesis of melanoma and nonmelanoma skin cancer.
AB  - The p53 tumor suppressor gene and gene product are among the most diverse and
      complex been shown to have a direct correlation with cancer development and have
      been shown to occur in nearly 50% of all cancers. p53 mutations are particularly
      common in skin cancers and UV irradiation has been shown to be a primary cause of
      specific 'signature' mutations that can result in oncogenic transformation. There
      are certain 'hot-spots' in the p53 gene where mutations are commonly found that
      result in a mutated dipyrimidine site. This review discusses the role of p53 from
      normal function and its dysfunction in precancerous lesions, nonmelanoma and
      melanoma skin cancers. Additionally, molecules that associate with p53 and alter
      its function to produce neoplastic conditions are also explored in this chapter.

PMID- 18348464
TI  - Apoptosis and pathogenesis of melanoma and nonmelanoma skin cancer.
AB  - Skin cancers, i.e., basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and
      melanoma, belong to the most frequent tumors. Their formation is based on
      constitutional and/or inherited factors usually combined with environmental
      factors, mainly UV-irradiation through long term sun exposure. UV-light can
      randomly induce DNA damage in keratinocytes, but it can also mutate genes
      essential for control and surveillance in the skin epidermis. Various repair and
      safety mechanisms exist to maintain the integrity of the skin epidermis. For
      example, UV-light damaged DNA is repaired and if this is not possible, the DNA
      damaged cells are eliminated by apoptosis (sunburn cells). This occurs under the
      control of the p53 suppressor gene. Fas-ligand (FasL), a member of the tumor
      necrosis superfamily, which is preferentially expressed in the basal layer of the
      skin epidermis, is a key surveillance molecule involved in the elimination of
      sunburn cells, but also in the prevention of cell transformation. However, UV
      light exposure downregulates FasL expression in keratinocytes and melanocytes
      leading to the loss of its sensor function. This increases the risk that
      transformed cells are not eliminated anymore. Moreover, important control and
      surveillance genes can also be directly affected by UV-light. Mutation in the p53
      gene is the starting point for the formation of SCC and some forms of BCC. Other
      BCCs originate through UV light mediated mutations of genes of the hedgehog
      signaling pathway which are essential for the maintainance of cell growth and
      differentiation. The transcription factor Gli2 plays a key role within this
      pathway, indeed, Gli2 is responsible for the marked apoptosis resistance of the
      BCCs. The formation of malignant melanoma is very complex. Melanocytes form nevi
      and from the nevi melanoma can develop through mutations in various genes. Once
      the keratinocytes or melanocytes have been transformed they re-express FasL which
      may allow the expanding tumor to evade the attack of immune effector cells. FasL
      which is involved in immune evasion or genes which govern the apoptosis
      resistance, e.g., Gli2 could therefore be prime targets to prevent tumor
      formation and growth. Attempts to silence these genes by RNA interference using
      gene specific short interfering RNAs (siRNAs) or short hairpin RNAs (shRNAs) have
      been functionally successful not only in tissue cultures and tumor tissues, but
      also in a mouse model. Thus, siRNAs and/or shRNAs may become a novel and
      promising approach to treat skin cancers at an early stage.

PMID- 18348465
TI  - Treatment of melanoma and nonmelanoma skin cancer.
AB  - The incidence of skin cancer is increasing in Caucasian populations worldwide.
      Treatment approaches for Nonmelanoma skin cancer (NMSC) are predominantly
      curative and surgery can be regarded as standard of care. Nevertheless, novel and
      less invasive topical therapy modalities like photodynamic therapy or local
      immune modifiers are in progress. In contrast to NMSC, the mortality of melanoma
      has not changed considerably over the last years and decades. Melanoma survival
      mainly depends on primary tumor thickness underlining the importance of primary
      and secondary prevention by avoidance or early detection of the disease. The
      chance to cure melanoma patients is steadily decreasing with tumor stage. As the
      prognosis in distant metastatic disease is still poor, except for single
      situations therapy approaches are palliative and accompanied by an optimal
      supportive care of the patients concerned. Albeit removal of localized metastases
      is currently the most effective approach in metastatic melanoma, chemo- and
      chemoimmunotherapy has to be regarded as standard treatment in most of the cases.
      Novel and promising therapeutic options accrue from growing insights in tumor
      biology and immunology. Not only in melanoma, development and application of
      targeted therapies currently attract the most attention in the treatment of
      advanced tumors. First clinical experiences with those antiproliferative,
      antiangiogenic and proapoptotic agents reveal only moderate antitumoral activity
      in melanoma, so that future efforts aim at defining more effective combination
      strategies using chemo-, targeted and vaccination therapy approaches.

PMID- 18348466
TI  - Pharmacokinetics of huperzine A following oral administration to human
      volunteers.
AB  - The objective of the present study was to investigate the in vivo
      pharmacokinetics of huperzine A in healthy human volunteers. Twelve subjects (M
      6, F 6; age ranged from 20-25 years) participated in the study. Huperzine A was
      administered in tablet form at a single dose of 0.4 mg. Following oral
      administration, the presence of huperzine A started to appear in the plasma at 5
      10 min, and reached the peak concentrations with a Cmax of 2.59 +/- 0.37 ng/ml at
      58.33 +/- 3.89 min (time to reach peak level, Tmax. The area under plasma vs time
      curve (AUC(0-t)) and the area under plasma from zero to infinity (AUC(0-infinity)
      for huperzine A were found to be 1986.96 +/- 164.57 microg/l.min and 2450.34 +/-
      233.32 microg/l.min, respectively. The results of this study indicated that the
      pharmacokinetics of huperzine A conformed to a two-compartmental open model. The
      mean values of alpha and the beta half-life were 21.13 +/- 7.28 min and 716.25 +/
      130.18 min respectively, and showed a biphasic profile with rapid distribution
      followed by a slower elimination rate.

PMID- 18348467
TI  - Pharmacokinetics of etoposide in rats with uranyl nitrate (UN)-induced acute
      renal failure (ARF): optimization of the duration of UN dosing.
AB  - A uranyl nitrate-induced model of acute renal failure (UN-ARF) for various time
      periods was used to study its effect on the disposition of several drugs like
      chlorzoxazone, clarithromycin, vancomycin, methotrexate etc. An attempt to
      optimize the duration of UN dosing with respect to the pharmacokinetics of
      etoposide in rats was carried out after intravenous (i.v.) dosing of UN at 5
      mg/kg for 1, 3, 5 and 7 days. Irrespective of the duration of UN dosing apart
      from day 1, ARF was observed, with significantly increased serum levels of
      creatinine (0.36 +/- 0.11 for controls vs 2.44 +/- 0.72 [day 7] for UN-ARF rats)
      and urea (33.71 +/- 9.46 for controls vs. 169.2 +/- 9.71 [day 5] for UN-ARF rats)
      in all the UN-treated groups. It has been reported that ARF may alter the
      pharmacokinetics (PK) and the exposure of renally eliminated drugs. Further, as
      exposure to etoposide has a correlation with toxicity, the need to investigate
      the possible alterations in etoposide pharmacokinetics in the UN-ARF model could
      be of significance. The PK of etoposide was therefore investigated in control and
      UN-ARF rats after a single i.v. dose of 25 mg/kg. The concentrations of etoposide
      in the plasma were determined by high- performance liquid chromatography (HPLC)
      method with fluorescence detector set at excitation and emission wavelengths of
      380 and 520 nm respectively. The metabolic stability of etoposide was
      investigated in rat liver microsomes prepared from control and UN-ARF treated
      rats. The PK results showed increased plasma levels and systemic exposure to
      etoposide (19.97 +/- 2.12 for control vs 29.03 +/- 2.32, 34.45 +/- 3.37, 34.19 +/
      2.98 for 3, 5 and 7day UN-treated groups respectively), i.e. for all UN-ARF
      groups except for 1-day UN-ARF rats (20.06 +/- 1.53). Incubation with liver
      microsomes from UN-ARF rats treated for up to 5 days and control rats showed no
      significant difference in etoposide metabolism suggesting that the CYP3A4
      isoenzyme responsible for the metabolism of etoposide was not considerably
      expressed thereby leading to the conclusion that 3 days UN dosing was sufficient
      to induce ARF in rats, and that the dose of etoposide required needs to be
      monitored due to altered PK.

PMID- 18348468
TI  - HPLC analysis of in vivo metabolites of 4-nitrobenzoic acid [(5-nitro-2
      thiopheneyl)methylene]hydrazide in rats.
AB  - The in vivo metabolism of 4-nitrobenzoic acid [(5-nitro-2
      thiopheneyl)methylene]hydrazide (substrate), a model that represents hydrazide
      hydrazone compounds, was investigated in the rat. The metabolites were monitored
      in rat plasma at certain time intervals. The substrate was dissolved in
      dimethylsulfoxide (DMSO)/water (1:4) and administered intraperitoneally at dose
      of 100 mg/kg and 500 mg/kg. Blood samples were collected at 30 min, then at 1,2,
      4, 8, 12 and 24 h post-administration. The chromatographic separation of the
      substrate and its metabolites was performed on aNovapak C18 (Phenomenex) (150 mm
      x 4.6 mm i.d., 5-microm particle size) using a mobile phase consisting of
      phosphate buffer: acetonitrile (90:10, v/v) with a linear gradient system. From
      the biotransformation of this compound, 4-nitrobenzoic acid (M3) was identified
      together with the substrate, as evidenced by high pressure liquid chromatography
      (HPLC)-UV/diode array detection (DAD).

PMID- 18348469
TI  - The effect of four different types of diet on the bioavailability of loracarbef.
AB  - This randomized open-label single-dose crossover pharmacokinetic study was
      carried out to assess the effect of different diets on the bioavailability of
      loracarbef in 24 healthy male volunteers. A single dose of loracarbef in 200-mg
      tablet form was administered at 5 different times: after overnight fasting, after
      two vegetarian (high-fat and low-fat) diets, and following two non-vegetarian
      (high-fat and low-fat) diets. Serial blood samples were collected up to 10 h post
      dose. Serum loracarbef concentrations were determined by a validated high
      performance liquid chromatographic (HPLC) method. Area under curve (AUC) values
      were significantly affected only by non-vegetarian diets; however the time to
      reach maximum serum concentration (Tmax) was prolonged and the maximum serum
      concentration (Cmax was decreased by all types of meals. The non-vegetarian diets
      affected the rate of absorption of loracarbef more than the vegetarian diets. The
      lowest decrease in Cmax was produced by the high-fat vegetarian diet, while the
      maximum was produced by the low-fat non-vegetarian diet. The results of this
      study indicate that while the rate of loracarbef absorption is significantly
      decreased by all diets, the extent of absorption is only reduced significantly by
      the non-vegetarian diets. The rate of elimination (k(el)) was not found to be
      significantly decreased by any of the diets. As compared to the high-fat non
      vegetarian diet, the time beyond minimum inhibitory concentration (MIC90)
      concentration was significantly increased by the high-fat vegetarian diet. The
      implications of these findings for the large Indian vegetarian population are
      considerable.

PMID- 18348470
TI  - In vitro binding of lidocaine to liver tissue under the influence of propranolol:
      another mechanism of interaction?
AB  - The co-administration of lidocaine and propranolol leads to significant drug-drug
      interactions. Beta-blockers decrease liver perfusion and inhibit the activity of
      hepatic microsomal lidocaine metabolizing enzymes of the P450_2D subfamily.
      Hence, there is a resulting reduction in the hepatic breakdown of lidocaine and
      an increase in its serum concentrations. In this study the ability of propranolol
      to displace lidocaine from its binding sites in liver tissue has been examined
      through an in vitro model. Rat liver slices were incubated together with
      propranolol and/or lidocaine in human serum and the percentage of the bound
      fraction of lidocaine in the experimental mixture was assessed. The present
      results indicate that propranolol significantly decreases the binding process of
      lidocaine in liver tissue. This effect develops only when blood is used as
      incubation medium and the incubation period lasts 60 min. In conclusion,
      propranolol can displace lidocaine from liver proteins and therefore the co
      administration of the two drugs may increase the free fraction of lidocaine
      excreted by the liver. However, this result arises from an in virro model and
      thus further investigation is needed.

PMID- 18348471
TI  - Influence of cefoperazone and azithromycin on the pharmacokinetics of
      pazufloxacin in rats.
AB  - The effects of cefoperazone and azithromycin administered separately on the
      pharmacokinetics of pazufloxacin (PZFX) mesilate were investigated in rats.
      Animals were injected with cefoperazone at a high dose (180 mg/kg) or
      azithromycin at a dose of 45 mg/kg through the tail vein 10 min before
      intravenous (i.v.) administration of PZFX (45 mg/kg). Blood concentrations of
      PZFX were determined by HPLC. Parameters relating to the pharmacokinetic
      interaction between PZFX and cefoperazone or azithromycin were estimated by a two
      compartmental model. The experimental results showed that the presence of
      azithromycin significantly delayed the t(1/2 beta) and mean residence time (MRT)
      of PZFX in the plasma. However, no significant changes between the control group
      and the cefoperazone-treated animals in the pharmacokinetic parameters of PZFX,
      such as t(1/2 beta), volume of distribution (Vd), area under the curve (AUC) and
      the clearance (Cl) were observed.

PMID- 18348472
TI  - High pressure liquid chromatographic analysis of in vivo metabolites of N
      (substituted phenyl)-N'-(1,3,5-trimethyl pyrazole-4-yl)thioureas in rats.
AB  - The aim of this study was to investigate the in vivo metabolism of N-(substituted
      phenyl)-N'-(1,3,5-trimethylpyrazole-4-yl)thioureas (substrate) as model compounds
      in rats via HPLC. The substrates, N-(4-fluoro/chlorophenyl)-N'-(1,3,5
      trimethylpyrazole-4-yl)thioureas (T2 and T3), and their possible metabolites were
      synthesized and the structures of the compounds were elucidated both by spectral
      and elemental analysis. Substrates were dissolved in 5% gum arabic and
      administered 100 mg/kg intraperitoneally (i.p.) in a volume of 0.1 ml/100 g.
      Blood samples were withdrawn before and at 30 min, 1, 2, 4, 8, 12 and 24 h post
      dose. Chromatographic separation of the substrate and its metabolites was
      performed using a Hichrom chromasil C18 column (150 mm x 4.6 mm i.d., 5 microm
      particle size). The optimal composition of the mobile phase was achieved by using
      different mixtures of pure methanol and water. From the biotransformation of
      these thiourea compounds, N-dealkylation metabolites N-(4-fluoro/chloro-phenyl)
      N'-(3,5-dimethylpyrazole-4-yl)thioureas (TI and T4) were identified together with
      unchanged substrate (T2 and T3) in the plasma by comparing them to reference
      standards via HPLC UV/DAD.

PMID- 18348473
TI  - Identification of CYP3A4 as the primary cytochrome P450 responsible for the
      metabolism of tandospirone by human liver microsomes.
AB  - The present study was carried out to characterize the human P450 isoforms
      involved in the metabolism of tandospirone, an anxiolytic agent known for its
      superior efficacy and safety. Among 11 yeast-expressed recombinant P450 isoforms
      tested, CYP2D6 and CYP3A4 exhibited the highest tandospirone metabolic activity.
      Although there was no qualitative difference between the two isoforms, a
      quantitative difference in metabolite profiling was found i.e., M4 (hydroxylation
      of the pyrimidine ring) was the major metabolite formed with CYP2D6 while M2
      (hydroxylation of the norbornan ring) and 1-PP (oxidative cleavage of the butyl
      chain) predominated with CYP3A4. The metabolite profile on incubation with CYP3A4
      was qualitatively and quantitatively similar to that obtained with human liver
      microsomes. In vitro intrinsic clearance (CLint) values derived from kinetic
      analysis using both P450 isoforms were similar (2.2 and 1.6 ml/min/nmol P450),
      but the hepatic content of CYP3A4 was found to be more abundant than that of
      CYP2D6. The in vitro metabolism of tandospirone by human liver microsomes was
      markedly inhibited by ketoconazole (a CYP3A4 inhibitor) but not by quinidine (a
      CYP2D6 inhibitor). These results indicate that the metabolism of tandospirone by
      human liver microsomes primarily involves CYP3A4, and to a lesser extent CYP2D6.

PMID- 18348474
TI  - Ethical obligations of physicians participating in public health quarantine and
      isolation measures.
AB  - In dealing with outbreaks of communicable diseases, the medical profession should
      work with public health authorities to promote the use of interventions that
      achieve desired public health outcomes with minimal infringement upon individual
      liberties. This article endeavors to help physicians manage their dual
      responsibilities to their patients and to their communities when participating in
      appropriate quarantine and isolation measures. In implementing such measures,
      individual physicians should take necessary actions to promote patients' well
      being. In addition, the medical profession and individual physicians share
      responsibility for taking appropriate precautionary measures to protect the
      health of individuals caring for patients with communicable diseases.

PMID- 18348475
TI  - Addressing poverty as risk for disease: recommendations from CDC's consultation
      on microenterprise as HIV prevention.
AB  - In March 2006, the Centers for Disease Control and Prevention (CDC) convened a
      consultation meeting to explore microenterprise as a potential human
      immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) prevention
      intervention. The impulse to link microenterprise with HIV/AIDS prevention was
      driven by the fact that poverty is a significant factor contributing to the risk
      for infection. Because increasingly high rates of HIV infection are occurring
      among women, particularly among poor African American women in the southern
      United States, we focused the consultation on microenterprise as an intervention
      among that population. In the international arena, income generated by
      microenterprise has contributed to improving family and community health
      outcomes. This article summarizes the contributions made to the consultation by
      participants from the diverse fields of microenterprise, microfinance, women's
      studies, and public health. The article ends with recommendations for HIV/AIDS
      prevention and, by implication, addressing other public health challenges,
      through the development of multifaceted intervention approaches.

PMID- 18348476
TI  - A model for surveillance of methicillin-resistant Staphylococcus aureus.
AB  - It is well recognized that methicillin-resistant Staphylococcus aureus (MRSA) has
      become a community pathogen. Several key differences between community-associated
      and hospital-associated MRSA strains exist, including distinct methicillin
      resistance genes and genetic backgrounds and differing susceptibility to
      antibiotics. Recent studies have demonstrated that typical hospital and community
      strains easily move between hospital and community environments. Despite evidence
      of MRSA's expanding reach in the community, the best methods for population-level
      detection and containment have not been established. In an effort to determine
      effective methods for monitoring the spread of MRSA, we reviewed the literature
      on hospital-associated and community-associated MRSA (CA-MRSA) in the community
      and proposed a model for enhanced surveillance. By linking epidemiologic and
      molecular techniques within a surveillance system that coordinates activities in
      the community and health-care setting, scientists and public health officials can
      begin to measure the true extent of CA-MRSA in communities and hospitals.

PMID- 18348477
TI  - Reducing levels of toxic chemicals in cigarette smoke: a new Healthy People 2010
      objective.
AB  - We developed and implemented a national surveillance system to monitor and reduce
      the levels of toxicchemicals in tobacco smoke. A developmental Healthy People
      2010 (HP 2010) objective was revised to report on levels of three categories of
      chemicals--tobacco-specific nitrosamines, polyaromatic hydrocarbons, and volatile
      organic compounds--in the smoke of leading U.S. cigarette brands. Unit-based
      sales-weighted average levels were calculated for each chemical category. The
      target for the new HP 2010 objective is a 10% reduction in unit-based sales
      weighted average levels of each chemical category. The Centers for Disease
      Control and Prevention provided the baseline, target data, and laboratory
      analyses. A national data source, national baseline data, and target were
      presented to the Healthy People Steering Committee during 2005 Midcourse Review.
      Approval of the revised objective initiated the surveillance of three major
      classes of toxic chemicals in cigarette smoke. The approved objective provides a
      feasible, innovative approach for monitoring and supporting measurable population
      based reductions in levels of toxic and carcinogenic chemicals in tobacco smoke.

PMID- 18348478
TI  - The San Diego Immunization Survey: a model for local vaccination coverage
      assessment.
AB  - OBJECTIVES: Assessing vaccination coverage as part of a comprehensive
      intervention has been demonstrated to result in increased coverage rates. The
      National Immunization Survey provides coverage estimates at the national level
      and selected urban areas. However, it is important for other localities to
      understand vaccination coverage in their areas. The San Diego Immunization Branch
      conducts the San Diego Immunization Survey (SDIS) to gather vaccination coverage
      information in San Diego County. This article describes the methodology and
      results of the SDIS. METHODS: The SDIS is a two-phase immunization survey. The
      first phase is a random-digit-dialing survey in which vaccination information is
      obtained by phone. The second phase involves the verification of this information
      and/or obtaining vaccination information via the registry or the child's
      provider(s). RESULTS: In 2005, the sample size included 839 respondents. From
      1995 to 2005, coverage for the following individual vaccines increased:
      diphtheria and tetanus toxoids, and acellular pertussis (92.0% to 96.5% for > or
      = 3 doses, and 75.0% to 89.0% for > or = 4 doses), polio (83.0% to 94.7%),
      measles-mumps-rubella (85.0% to 95.8%), Haemophilus influenzae type b (87.0% to
      93.2%), and hepatitis B (67.0% to 93.6%). CONCLUSION: The results of the SDIS
      demonstrate that San Diego County has exceeded the Healthy People 2010 goal to
      reach at least 80% coverage for the series of universally recommended
      vaccinations.

PMID- 18348479
TI  - A comparison of health-related quality of life for individuals with mental health
      disorders and common chronic medical conditions.
AB  - OBJECTIVES: The purpose of this study was to compare the burden of disease
      experienced by people with mental health conditions with people who have common
      medical disorders. Three prevalent medical disorders--the burden of disease of
      back/neck problems, diabetes, and hypertension--were compared with the mental
      health category of depression, anxiety, or emotional problem. METHODS: This study
      used data from the nationally representative 2003-2004 National Health and
      Nutrition Examination Survey for respondents aged 18 or older (n = 4,833). The
      measurement of health-related quality of life (HRQOL) used was the Healthy Days
      Measures developed by the Centers for Disease Control and Prevention. Unadjusted
      and adjusted HRQOL were compared for individuals reporting each of the four
      conditions. Adjusted HRQOL was assessed using ordinary least squares regression,
      which controlled for gender, age, race/ethnicity, education, marital status,
      comorbidity, and income. RESULTS: Individuals with mental health conditions
      experienced 17.6 total unhealthy days per month, while those with back and neck
      problems and those with hypertension experienced 12.2 total unhealthy days per
      month, and those with diabetes experienced 12.3 total unhealthy days per month.
      After adjusting for socioeconomic and demographic characteristics as well as
      comorbid conditions, mental health conditions were responsible for a 6.8-day
      decrease in healthy days per month compared with average adults (p < 0.001).
      Mental health conditions resulted in significantly lower HRQOL than back or neck
      problems (p = 0.053), diabetes, (p = 0.002), and hypertension (p = 0.012).
      CONCLUSIONS: There were significant differences between the HRQOL found in mental
      and medical conditions, with mental health conditions being responsible for
      significantly greater impairment of HRQOL. An efficient health-care system should
      consider the relative disease burden of specific conditions when allocating
      public health resources.

PMID- 18348480
TI  - Safety of upper-room ultraviolet germicidal air disinfection for room occupants:
      results from the Tuberculosis Ultraviolet Shelter Study.
AB  - OBJECTIVES: We evaluated the safety of room occupants in the Tuberculosis
      Ultraviolet Shelter Study (TUSS), a double-blind, placebo-controlled field trial
      of upper-room ultraviolet germicidal irradiation (UVGI) at 14 homeless shelters
      in six U.S. cities from 1997 to 2004. METHODS: Data collection involved
      administering questionnaires regarding eye and skin irritation to a total of
      3,611 staff and homeless study subjects. RESULTS: Among these subjects, there
      were 223 reports of eye or skin symptoms. During the active UV period, 95
      questionnaires (6%) noted such symptoms, and during the placebo period, 92
      questionnaires (6%) did so. In the 36 remaining cases, either the UV period when
      symptoms took place was unknown or the symptoms spanned both periods. There was
      no statistically significant difference in the number of reports of symptoms
      between the active and placebo periods. One definite instance of UV-related
      keratoconjunctivitis occurred, resulting from a placement of a bunk bed in a
      dormitory where a single bed had been used when the UV fixtures were first
      installed. CONCLUSIONS: These findings demonstrate that careful application of
      upper-room UVGI can be achieved without an apparent increase in the incidence of
      the most common side effects of accidental UV overexposure.

PMID- 18348481
TI  - Weather and the transmission of bacillary dysentery in Jinan, northern China: a
      time-series analysis.
AB  - OBJECTIVES: This article aims to quantify the relationship between weather
      variations and bacillary dysentery in Jinan, a city in northern China with a
      temperate climate, to reach a better understanding of the effect of weather
      variations on enteric infections. METHODS: The weather variables and number of
      cases of bacillary dysentery during the period 1987-2000 has been studied on a
      monthly basis. The Spearman correlation between each weather variable and
      dysentery cases was conducted. Seasonal autoregressive integrated moving average
      (SARIMA) models were used to perform the regression analyses. RESULTS: Maximum
      temperature (one-month lag), minimum temperature (one-month lag), rainfall (one
      month lag), relative humidity (without lag), and air pressure (one-month lag)
      were all significantly correlated with the number of dysentery cases in Jinan.
      After controlling for the seasonality, lag time, and long-term trend, the SARIMA
      model suggested that a 1 degree C rise in maximum temperature might relate to
      more than 10% (95% confidence interval 10.19, 12.69) increase in the cases of
      bacillary dysentery in this city. CONCLUSIONS: Weather variations have already
      affected the transmission of bacillary dysentery in China. Temperatures could be
      used as a predictor of the number of dysentery cases in a temperate city in
      northern China. Public health interventions should be undertaken at this stage to
      adapt and mitigate the possible consequences of climate change in the future.

PMID- 18348482
TI  - A profile of state-level differences in the oral health of people with and
      without disabilities, in the U.S., in 2004.
AB  - OBJECTIVES: The aim of this study was to provide state-level surveillance data
      assess the oral health of people with disabilities. METHODS: Data from the 2004
      Behavioral Risk Factor Surveillance System (BRFSS)--a state-based, random-digit
      dialed telephone survey of the U.S. civilian noninstitutionalized population 18
      years of age and older--were used to estimate disability prevalence and state
      level differences in oral health among people with and those without
      disabilities. RESULTS: Nationally, people with disabilities were less likely than
      people without disabilities to visit a dentist or dental clinic in the past year.
      The percentage of people with disabilities who reported they had visited a
      dentist in the past year was lowest in Mississippi (48.9%) and highest in
      Connecticut (74.5%). Among people without disabilities reporting they had visited
      a dentist or dental clinic in the past year, the percentage was lowest in
      Mississippi (60.7%) and highest in Minnesota (80.7%). Edentulism was higher among
      people with disabilities compared with those without disabilities. Among people
      with disabilities, edentulism was lowest in the District of Columbia (4.1%) and
      highest in Kentucky (18.7%). Among people without disabilities, edentulism was
      lowest in California (2.7%) and highest in Kentucky (11.3%). CONCLUSIONS: Despite
      numerous studies and reports documenting the unmet oral health needs of people
      with disabilities, there has been no systematic national surveillance of oral
      health among people with disabilities in the United States. This article provides
      much-needed state-by-state and national epidemiologic data regarding the oral
      health of people with disabilities.

PMID- 18348483
TI  - Converting a potential agency crisis into community success: mercury recycling
      program following elemental mercury exposures in Amarillo, Texas, 2004.

PMID- 18348484
TI  - Beryllium's public relations problem: protecting workers when there is no safe
      exposure level.

PMID- 18348485
TI  - Ensuring the use of federal assets in public health emergencies: the role of the
      Federal Tort Claims Act in enabling the responsiveness of federally funded
      community health centers.

PMID- 18348486
TI  - On linkages: using exercises to identify systems-level preparedness challenges.

PMID- 18348487
TI  - On academics: perspectives on the future of academic public health practice.

PMID- 18348488
TI  - [Montesquieu, sciences and medicine in Europe].
AB  - Montesquieu is the first one of his century to be fascinated by sciences, chiefly
      by sciences of life. He created a prize of plysics and anatomy, used the
      microscope and even made experiments. Despite his amblyopia and his cataract
      which made him blind, he was in contact with the intellectual and scientific
      elite of his time. He has been an innovator through his interest about public
      health and professional diseases.

PMID- 18348489
TI  - [Theophilus of Bordeu (1722-1776). A man of spirit, eclectic knowledge and
      fascinating brilliance].
AB  - A member of a medical family, Theophile de Bordeu (1722-1776) studied and worked
      in southwestern France, then in Paris. He was acquainted both with the Royal
      Court and the Encyclopedists and was very "a la mode". His main book was his
      Recherches anatomiques sur la position des glandes, et sur leur action published
      in 1752. Elegant and brilliant, he has been a good precursor in many medical
      fields.

PMID- 18348490
TI  - [Gilbert Ballet (1853 - 1916). Reasonable psychiatry].
AB  - Gilbert Ballet (1853-1916) was born into a medical family in the French province
      of Limousin. He completed a brilliant career in Paris hospitals: Resident (1875),
      Assistant to Professor Charcot of Salpetriere Hospital (1882), Consultant (1884),
      Head of the Department of Neurology and Psychiatry (1890), and member of the
      Franch Academy of Medicine (1812). He had been teaching in the "Brain and mental
      diseases" course since 1891. In 1909, he held the chair of history of medicine.
      In 1911, he was Professor of mental diseases. He then advocated that nervous
      system disorders constituted a single thematic domain with two branches, organic
      neurology and psychiatry. He wrote a famous report on the forensic medicine
      assessment of criminal responsibility. His motto was "Let's use psychology as we
      can, not forgetting that we are physicians".

PMID- 18348491
TI  - [Dr. Edmond Locard (1877-1966), the Sherlock Holmes of Lyons].
AB  - Doctor Edmond Locard (1877-1966), a French forensic scientist, a disciple of
      famous Professor Alexandre Lacassagne, created in Lyons, in 1910, the first
      French laboratory of technical police. During more than fourty years, he used and
      developed new scientific techniques (fingerprint identification, study of marks
      and dust...) in order to help the policemen and judges to solve the most horrible
      crimes.

PMID- 18348492
TI  - [Bouchardat and hygienic medicine].
AB  - Bouchardat (1806-1886) got his medical degree in Paris in 1832. As chief
      pharmacist at the Hotel-Dieu (Paris), he set up chemical analysis for blood and
      urine. He inaugurated medical analysis and biochemistry, investigating the
      digestive process on dogs. In 1852, he was made as professor for hygiene at the
      Faculty of medicine. Then, he taught for fourty years, publishing extensive works
      on pharmacology, toxicology, nutrition and agronomics. He gave a modern view on
      individual and collective needs for food that he considered as the main aspect of
      hygiene. He was a member of the Academie de medecine and the Societe centrale
      d'agriculture.

PMID- 18348493
TI  - [Apollinaire Bouchardat and diabetes].
AB  - Apollinaire Bouchardat (1806-1886) begins its hospital formation by the pharmacy
      internship and then starts his medical studies. He becomes chief pharmacist of
      the Hotel-Dieu in 1835 and during 20 years, he devotes his life to the study of
      diabetes. Through observations and experiments, he builds new concepts allowing
      to establish the bases of clinical diabetology due to a solid competence in
      fundamental sciences and his intelligence in semiologic observations. He studied
      urine glucose as a reflect of the clinical state of the patients and, in order to
      carry out its exact measurement, he recommended the use of the polarimeter. He
      engaged himself in many studies concerning well as the patients diet as to their
      way of life. Thus he recommended a large decrease in starchy foods and sugars, he
      encouraged physical exercise and considered that, since the assumption of
      responsibility of the diabetic was serious, it could foresee the remission of
      disease. Due to encouraging results, he developed self-monitoring by the patients
      by the means of simple chemical reagents, convinced that making patients
      responsible, despite difficulties of the diet, could modify their attitude.
      Precursor of the modern diabetology, one can consider that he founded it as a
      true medical discipline. Its major work: De la Glycosurie ou diabete sucre, son
      traitement hygenigue is pro-bably the first textbook on diabetes, associating
      clinical observations, experimental steps and proposals for a treatment based on
      the patients' way of life: mainly diet and exercise: still preached steps, a
      hundred and fifty years later.

PMID- 18348494
TI  - [The sanitary situation on board the vessels of the "VOC", at the Cape of Good
      Hope and in Batavia between 1750 and 1800].
AB  - During the second half of the eighteenth century the Dutch East India Company got
      more and more worried about the worsening sanitary situation aboard its vessels,
      at the Cape of Good Hope and in Batavia. Several plans were submitted to the
      directors of the company, aiming at the improvement of this situation. In 1768,
      J.C.M. Radermacher, a member of the Council of India, proposed the construction
      of a new hospital at the Cape of Good Hope (based on the building plan of the
      Hotel-Dieu in Paris, as well as the improvement of the European hospitals in
      Batavia, the Buiten-Hospitaal. Nevertheless, the sanitary situation soon worsened
      again, as a consequence of the impoverishment of the Company.

PMID- 18348495
TI  - [Pharmaceutical and parapharmaceutical advertising of Annales vertes in 1927].
AB  - The journal Les Annales, under the direction of Adolphe Brisson, was deeply
      modified by Pierre (Adolphe's son) who decided to publish in 1927 the first issue
      of Les Annales with a green cover, so called Les Annales vertes. This journal
      contained a lot of pharmaceutical as well as parapharmaceutical advertising. It
      is the useful to make an analysis of it at a period which is just preceding the
      1929 financial krasch and which is characterized by large advertising budgets in
      the pharmaceutical industry. Directed toward the general population, advertising
      was mainly targeting women and patients suffering from anaemia, intestinal
      transit diseases, or corn. It is also an opportunity to observe the dynamism of
      some pharmaceutical companies, most of which have disappeared since then. This
      very large amount of advertising, indeed in excess, will drive ultimately to
      change the law a few years later in order to control more and more tightly this
      activity of advertising that targeted the general population as well as medical
      doctors and pharmacists.

PMID- 18348496
TI  - [Turpentined vapour baths with coniferous oil].
AB  - This article presents the history of turpentined vapour baths used to treat
      rheumatismes. In the same time appeared patent medicines made with coniferous
      oil, sold by chemist near those baths establishments.

PMID- 18348497
TI  - [Genealogical study of the Pijart dynasty, goldsmiths or apothecaries in Paris in
      the 16th and 17th centuries].
AB  - The Pijart dynasty, established in Paris during the 16th and 17th centuries,
      included apothecaries and goldsmiths who had a common ancestor, Michel Pijart,
      warden of the goldsmith's guild (garde de l'orfevrerie) in 1507. He was married
      to Jehanne Daumont and died 23rd July 1524. This couple had four sons, all
      goldsmiths, Pierre, Michel, Jehan and Nicolas. Pierre married twice. His first
      wife, Philippe Dusseau, was the sister of a famous apothecary. Only their eldest
      son, Francois, chose the profession of apothecary; the other three, Jacques,
      Jehan and Philibert, all followed their father's profession. By his second
      marriage to Marie de Mezieres, Pierre had two sons, Claude the elder and Claude
      the younger, who both became goldsmiths. Thus, the goldsmith's trade became the
      favoured profession of the Pijart family. Professional endogamy prevailed in this
      dynasty, after the fashion of merchants belonging to the six most prestigious
      guilds (Six-Corps de metiers). Goldsmiths and apothecaries retained strong family
      ties, demonstrated by family reunions (baptisms, betrothals, etc.). It is
      undisputable that the renown of this dynasty is based on the fame of its
      goldsmiths. However, through marriage, the Pijart's developed links with other
      families of apothecaries, of which the most outstanding were the Boulduc's.

PMID- 18348498
TI  - [1840 Pharmaceutical formulary for use by Tours' Bureau of Charity].
AB  - Presentation and analysis of the Pharmaceutical form wrote in 1840 by Medicinal
      Society of Indre et Loire department for the use of Tours' Charitable office.

PMID- 18348499
TI  - [The accident and death of King Stanislas at Luneville in February 1766. The
      drugs used for his burns and his embalmment. Reflections on this treatment].
AB  - Early in the morning of february 5th, 1766, King Stanislas, Duke of Lorraine and
      Bar, 88 years old, is seriously burned after a fall near the fire-place of his
      room. The medical treatment carried out by his physicians aims to cure his burns,
      but also to avoid infection and sustain his general state. But Stanislas dies on
      february 23th, probably of septicemia and major metabolic abnormalities. After
      the description of the accident, of the treatment and of the evolution of king's
      state, the paper studies the composition and effect hoped of the drugs
      administered with respect to the ideas and knowledges of this moment. Then some
      words are devoted to Jean-Gaspard Vockel, the apothecary of the king, the
      probable supplier of the drugs and the proved supplier of the products used for
      the embalmment. The last part of the paper offers a reflection on the treatment,
      on the possibility or not to save Stanislas, taking in account the importance of
      his burns, the current pathophysiological knowledges and the therapeutical
      measures which come from them that would have been taken today.

PMID- 18348500
TI  - Stanley J. Korsmeyer.

PMID- 18348501
TI  - Maclyn McCarty.

PMID- 18348502
TI  - [Networks and genesis of living beings: epistemologic perspectives].
AB  - Our paper focuses on Stuart Kauffman's theory from 1993 to 2004. Kauffman is
      looking for an explanation of the genesis of living beings by genetic networks.
      From interactions to cell types, Kauffman's viewpoint is concerned with
      differentiation and self-organization as network's properties. His approach of
      morphogenetic processes is interesting but it is insufficient. According to Sole,
      Fernandez and Kauffman [2003], networks would give an explanation of the
      diversity in patterns and cell types. Some other authors [as Perkins et al.,
      2004] consider that it is necessary to explore interactions, not with logical
      methods only, but non-linear systems too. Network's structure is related to
      biological diversity. It supposes genes' power's mediators within the cells and
      between them.

PMID- 18348503
TI  - [The history of the weekly revue Die medicinische Reform (1848/49) and exchange
      of letters between Rudolf Virchows and his publisher George Reimer].
AB  - The medical journal Medicinische Reform. Eine Wochenschrift edited by Rudolf
      Virchow and Rudolf Leubuscher in Berlin from July 1848 to June 1849 was in spite
      of its short life-time one of the most important and influential periodicals
      during the time of German revolution and medical reforms in the middle of the
      19th century. The paper gives a view of the history of edition of this ephemeral
      but outstanding journal as an essential source for our knowledge of the
      development of social medicine in Germany. Moreover it can be seen as an example
      for a new kind of modern scientific journals. Printing the Medicinische Reform
      through the years of revolution in 1848/49 was on the merits of the publishing
      house of Georg Reimer. In 1849 Virchow himself stopped editing the paper. Several
      reprints show the importance of the periodical for the history of siences (1879
      Berlin, partial by Virchow; 1975 Hildesheim; 1983 Berlin). The article ends with
      a first complete publication of the correspondence between Virchow and Reimer
      about the weekly Medicinische Reform.

PMID- 18348504
TI  - ["...primarily only for welfare and not for dentists" --"Reichszahnarztefuhrer"
      Ernst Stuck (1893-1974)].
AB  - From the very beginning German dentists and their scientific and professional
      organizations were involved in the disastrous developments following the Nazi
      assumption of power of 1933. After purging and both organisational and
      ideological streamlining which had been comparatively rapidly accomplished in
      1933/34 a development started which was characterized by extreme professional
      confrontation and lust for power in close entanglement with Nazi health policy
      objectives and deformation of scientific dentistry. A decisive role was assigned
      to the Reichszahnarztefuhrer Ernst Stuck (1893-1974) who was the highest
      representative of the dental profession throughout the Nazi Regime. However, up
      to the present his life and position has not been thoroughly researched. What is
      more, history of dentistry has been looking at his activities in a merely cursory
      and appeasing way. In fact, his function as Reichszahnarztefuhrer needs to be
      critically scrutinized and evaluated.

PMID- 18348505
TI  - ["Substances capable of self-reproduction" as cellular targets of chemical
      carcinogens].
AB  - In the course of studies on chemical carcinogenesis, which included animal
      experiments with a carcinogenic azo dye and a mathematical analysis of the
      observed effects, Hermann Druckrey and Karl Kupfmuller showed in 1948 that
      carcinogens induce heritable changes by targeting cellular "substances capable of
      self-reproduction". The authors did not discuss the chemical nature of these
      substances which remained unclear for a long time thereafter. It was not until
      1964 that deoxyribonucleic acid (DNA) was recognized, by Peter Brookes and Philip
      Lawley, as a target for the genotoxic action of chemical carcinogens. In
      retrospect, the results of Druckrey and Kupfmuller gave an early, indirect and
      until now not considered hint to an important role of DNA (the "substance")
      malfunction in the development of cancer, since DNA is the only molecule capable
      of self-reproduction. The results are now appreciated in light of the scientific
      knowledge available at the time.

PMID- 18348506
TI  - Professor HT (Harry) Howat: prime leader in pancreatology development in the UK.
AB  - Positioned in the posterior abdomen, the pancreas remained little observed until
      nineteenth century advances in physiology, followed later in the century by
      abdominal surgery, brought the organ into the clinical domain. The discovery of
      pancreatic stimulating hormones during the twentieth century culminated in the
      description of pancreozymin by Harper and Raper in Manchester in 1943. After
      World War II, Henry T Howat was appointed physician in that city and was able to
      analyse the results of hormonal stimulation in pancreatic disorders. He became
      the first doctor in Britain to specialise in pancreatology. His collaboration
      with colleagues in Britain and in Europe, through the evolution of specialist
      societies, encouraged the coordination of basic science, medicine, pathology,
      radiology and surgery, to further research in, and management of, pancreatic
      disease. Academic recognition by Manchester University resulted in his being
      appointed its first Professor of Gastroenterology and originator of a
      gastrointestinal research unit. As he pointed out, continuing scientific and
      technological advances influenced the concepts of disease, and moved the
      management of pancreatic disease from the general physician and surgeon to
      gastroenterologists. Howat's career illustrates the continuing specialisation
      witnessed in the latter half of the twentieth century.

PMID- 18348507
TI  - Stranger's fever in Charleston, South Carolina: a mistaken diagnosis?
AB  - George Augustus Clough was a young Englishman who died in Charleston, South
      Carolina, in 1843. The cause of death, which unusually was given on his
      gravestone, was Stranger's fever, which is now known to be yellow fever.
      Stranger's fever first appeared in North America in Florida in 1649, and
      continued to cause both sporadic cases as well as serious epidemics, mainly in
      the South and along the Eastern seaboard of the US until the beginning of the
      twentieth century. It gained its name from its propensity to mainly afflict
      recent arrivals, and Clough had only been in Charleston for two years before his
      death. However, a re-examination of the evidence suggests that he may not in fact
      have died of yellow fever.

PMID- 18348508
TI  - A family tradition of Scottish medicine.
AB  - In the late nineteenth and early twentieth centuries, Edinburgh was among the
      most popular of all destinations for South Africans seeking a medical education.
      Scotland was thus the fountainhead of much of the knowledge and skill that
      subsequently led to the development of a high standard of medical education in
      South Africa. This article describes how four members of a South African family
      received their medical education at the University and Royal Colleges of
      Physicians and Surgeons of Edinburgh and a fifth family member obtained the
      Membership of the Royal College of Physicians and was later elected to
      Fellowship. This is the story of a relationship spanning three generations
      between a family in which medicine had almost become a hereditary trait and the
      best of Scottish medical education.

PMID- 18348509
TI  - Physicians to the Duke of Clarence.
AB  - Halliday and Beattie came from the small village of Dalton in Dumfriesshire and
      both became physicians to the Duke of Clarence, the King's brother. They had
      interesting and varied careers and accompanied their royal patron on his frequent
      visits to the Continent. Halliday served in the Peninsula War and at Waterloo
      while Beattie became a close friend and confident of the Duke. Based on his
      visits to the Continent, Beattie produced a beautifully illustrated series of
      travel books.

PMID- 18348510
TI  - Characterization of nanogap chemical reactivity using peptide-capped gold
      nanoparticles and electrical detection.
AB  - Nanogaps are usually combined with synthetic or biological molecules to produce
      nanodevices having novel properties. This combination is better realized by
      controlling the chemical properties of the nanogap. We show here that the
      presence of a specific chemical group inside nanogaps (30-90 nm) can be probed
      electrically using 10 nm gold nanoparticles derivatized by complementary
      functional groups. 100-10(4)-fold current increases were observed following the
      site-specific insertion of gold nanoparticles into the nanogap.

PMID- 18348511
TI  - PepLine: a software pipeline for high-throughput direct mapping of tandem mass
      spectrometry data on genomic sequences.
AB  - PepLine is a fully automated software which maps MS/MS fragmentation spectra of
      trypsic peptides to genomic DNA sequences. The approach is based on Peptide
      Sequence Tags (PSTs) obtained from partial interpretation of QTOF MS/MS spectra
      (first module). PSTs are then mapped on the six-frame translations of genomic
      sequences (second module) giving hits. Hits are then clustered to detect
      potential coding regions (third module). Our work aimed at optimizing the
      algorithms of each component to allow the whole pipeline to proceed in a fully
      automated manner using raw nucleic acid sequences (i.e., genomes that have not
      been "reduced" to a database of ORFs or putative exons sequences). The whole
      pipeline was tested on controlled MS/MS spectra sets from standard proteins and
      from Arabidopsis thaliana envelope chloroplast samples. Our results demonstrate
      that PepLine competed with protein database searching softwares and was fast
      enough to potentially tackle large data sets and/or high size genomes. We also
      illustrate the potential of this approach for the detection of the intron/exon
      structure of genes.

PMID- 18348512
TI  - Metabonomic and metallomic profiling in the amniotic fluid of malnourished
      pregnant rats.
AB  - Epidemiology and studies in animal models have revealed that prenatal
      malnutrition is highly correlated with abnormal fetal neurodevelopment. We
      present here a combined metabonomic and metallomic profiling technique to
      associate the metabolic and trace-elemental composition variations of rat
      amniotic fluid (AF) in malnourished pregnant rats with the retardation of fetal
      rat neurodevelopment. The AF samples from three groups of pregnant Sprague-Dawley
      rats, which were fed either a normal diet, a low-protein diet, or "a famine
      diet", were subjected to GC/MS and ICP/MS combined with multivariate data
      analysis (MVDA). PCA scores plot of both GC/MS and ICP/MS data showed similar and
      unique metabolic signatures of AF in response to the different diets. Rats in the
      famine group released increased amounts of glycine, inositol, putrescine, and
      rubidium and decreased amounts of methionine, dopa, tryptophan, glutamine, zinc,
      cobalt, and selenium in the AF. These discriminable variations in the AF may
      indicate the abnormality of a number of metabolic pathways in fetal rats
      including the folate cycle and methionine pathway, the monoamine pathway, and tri
      iodothyronine (T3) metabolism. The abnormalities may be the result of metabolites
      or elemental differences or a combination of both. This study demonstrates the
      potential of combining profiling of small-molecule metabolites and trace elements
      to broaden the understanding of biological variations associated with fetal
      neurodevelopment induced by environmental perturbation.

PMID- 18348513
TI  - Recent developments of carbonic anhydrase inhibitors as potential anticancer
      drugs.

PMID- 18348514
TI  - New approach to measure protein binding based on a parallel artificial membrane
      assay and human serum albumin.
AB  - We report here a new, label-free approach to measure serum protein binding
      constants. The assay is able to measure HSA K d values in the milli-molar to
      micromolar range. The protein is not immobilized on any surface and the assay
      self-corrects for nonspecific adsorption. No mass balance is required to get
      accurate binding constants and it is not necessary to wait for equilibrium to
      extract the binding constant. The assay runs in a 96-well format using
      commercially available parts and is, therefore, relatively easy to implement and
      automate. As the chemical membranes used are not water permeable, there is no
      volume change due to the osmotic pressure and pretreatment (soaking) is not
      necessary. The concept can potentially be extended to other proteins and could
      thus serve as a label-free technique for general binding constant measurements.

PMID- 18348515
TI  - epigenetic multiple ligands: mixed histone/protein methyltransferase,
      acetyltransferase, and class III deacetylase (sirtuin) inhibitors.
AB  - A number of new compounds bearing two ortho-bromo- and ortho, ortho-dibromophenol
      moieties linked through a saturated/unsaturated, linear/(poly)cyclic spacer
      (compounds 1- 9) were prepared as simplified analogues of AMI-5 (eosin), a
      recently reported inhibitor of both protein arginine and histone lysine
      methyltransferases (PRMTs and HKMTs). Such compounds were tested against a panel
      of PRMTs (RmtA, PRMT1, and CARM1) and against human SET7 (a HKMT), using histone
      and nonhistone proteins as a substrate. They were also screened against HAT and
      SIRTs, because they are structurally related to some HAT and/or SIRT modulators.
      From the inhibitory data, some of tested compounds ( 1b, 1c, 4b, 4f, 4j, 4l, 7b,
      and 7f) were able to inhibit PRMTs, HKMT, HAT, and SIRTs with similar potency,
      thus behaving as multiple ligands for these epigenetic targets (epi-MLs). When
      tested on the human leukemia U937 cell line, the epi-MLs induced high apoptosis
      levels [i.e., 40.7% ( 4l) and 42.6% ( 7b)] and/or massive, dose-dependent
      cytodifferentiation [i.e., 95.2% ( 1c) and 96.1% ( 4j)], whereas the single
      target inhibitors eosin, curcumin, and sirtinol were ineffective or showed a weak
      effect.

PMID- 18348516
TI  - Polyaminohydroxamic acids and polyaminobenzamides as isoform selective histone
      deacetylase inhibitors.
AB  - A series of polyaminohydroxamic acids (PAHAs) and polyaminobenzamides (PABAs)
      were synthesized and evaluated as isoform-selective histone deacetylase (HDAC)
      inhibitors. These analogues contain a polyamine chain to increase affinity for
      chromatin and facilitate cellular import. Seven PAHAs inhibited HDAC >50% (1
      microM), and two PABAs inhibited HDAC >50% (5 microM). Compound 17 increased
      acetylated alpha-tubulin in HCT116 colon tumor cells 253-fold but only modestly
      increased p21 (waf1) and acetylated histones 3 and 4, suggesting that 17
      selectively inhibits HDAC 6. PABA 22 alone minimally increased p21 (waf1) and
      acetylated histones 3 and 4 but caused dose-dependent increases in p21 (waf1) in
      combination with 0.1 microM 5-azadeoxycytidine. Finally, 22 appeared to be a
      substrate for the polyamine transport system. None of these compounds were
      cytotoxic at 100 microM. PAHAs and PABAs exhibit strikingly different cellular
      effects from SAHA and have the potential for use in combination antitumor
      therapies with reduced toxicity.

PMID- 18348517
TI  - Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a
      pyrrolidine scaffold.
AB  - Infections with the human immunodeficiency virus, which inevitably lead to the
      development of AIDS, are still among the most serious global health problems
      causing more than 2.5 million deaths per year. In the pathophysiological
      processes of this pandemic, HIV protease has proven to be an invaluable drug
      target because of its essential role in the virus' replication process. By use of
      pyrrolidine as core structure, symmetric 3,4-bis-N-alkylsulfonamides were
      designed and synthesized enantioselectively from D-(-)-tartaric acid as a new
      class of HIV protease inhibitors. Structure-guided design using the cocrystal
      structure of an initial lead as starting point resulted in a second series of
      inhibitors with improved affinity. The binding modes of four representatives were
      determined by X-ray crystallography to elucidate the underlying factors
      accounting for the SAR. With this information for further rational design, the
      combination of suitable side chains resulted in a final inhibitor showing a
      significantly improved affinity of K(i) = 74 nM.

PMID- 18348518
TI  - New selective inhibitors of steroid 11beta-hydroxylation in the adrenal cortex.
      Synthesis and structure-activity relationship of potent etomidate analogues.
AB  - Derivatives of etomidate were evaluated as inhibitors of adrenal steroid 11beta
      hydroxylations. Stereoselective coupling by Mitsunobu produced chirally pure
      analogues to study the effect of configuration, modification of the ester, and
      substitution in the phenyl ring, with the aim to probe specific sites for
      introducing a radionuclide. Iodophenyl metomidate (IMTO) labeled with iodine-131
      served as radioligand for structure-affinity relationship studies. We have
      characterized the kinetic parameters of specific (131)I-IMTO binding on rat
      adrenal membranes and used the displacement of (131)I-IMTO binding to evaluate
      functionalized MTO analogues. Our results indicated that (1) ( R)-configuration
      is essential for high affinity, (2) highest potency resides in the ethyl, 2
      propyl, and 2-fluoroethyl esters, and (3) substitution of the phenyl ring is well
      tolerated. The clinically used inhibitors metyrapone and ketoconazole inhibited
      (131)I-IMTO binding with low affinity. Incubation of selected analogues with
      human adrenocortical NCI-h295 cells demonstrated a high correlation with the
      inhibitory effect on cortisol secretion.

PMID- 18348519
TI  - Effect of cobratoxin binding on the normal mode vibration within acetylcholine
      binding protein.
AB  - Recent crystal structures of the acetylcholine binding protein (AChBP) have
      revealed surprisingly small structural alterations upon ligand binding. Here we
      investigate the extent to which ligand binding may affect receptor dynamics.
      AChBP is a homologue of the extracellular component of ligand-gated ion channels
      (LGICs). We have previously used an elastic network normal-mode analysis to
      propose a gating mechanism for the LGICs and to suggest the effects of various
      ligands on such motions. However, the difficulties with elastic network methods
      lie in their inability to account for the modest effects of a small ligand or
      mutation on ion channel motion. Here, we report the successful application of an
      elastic network normal mode technique to measure the effects of large ligand
      binding on receptor dynamics. The present calculations demonstrate a clear
      alteration in the native symmetric motions of a protein due to the presence of
      large protein cobratoxin ligands. In particular, normal-mode analysis revealed
      that cobratoxin binding to this protein significantly dampened the axially
      symmetric motion of the AChBP that may be associated with channel gating in the
      full nAChR. The results suggest that alterations in receptor dynamics could be a
      general feature of ligand binding.

PMID- 18348520
TI  - Synthesis of [4.6.4.6]fenestradienes and [4.6.4.6]fenestrenes based on an 8pi-6pi
      cyclization-oxidation cascade.
AB  - Fenestranes are regarded as a particularly challenging synthetic targets, and
      only few syntheses have been reported in the recent past. These rare compounds of
      synthetic and theoretical interest are a class of tetracyclic skeletons, defined
      as doubly a,a'-bridged spiroalkanes. The reported results are focused on the
      synthesis of new and original [4.6.4.6]fenestradienes 3a-f and
      [4.6.4.6]fenestrenes 4a-e. Our approach implies the formation of this tetracyclic
      structure by a reaction cascade, based on consecutive transformations starting
      from the trienyne 1a-f: an initial soft hydrogenation using a P-2 Nickel catalyst
      at room temperature, followed by a conrotatory 8p electrocyclization and a
      disrotatory 6p electrocyclization and a final oxidation. Several examples of this
      type of new compounds are described in this Communication.

PMID- 18348521
TI  - High-density DNA alignment on an Au(111) surface starting from folded DNA.
AB  - High-density uniform DNA alignment on a metal substrate is essential for creating
      sensitive DNA devices. We develop a self-sensing DNA alignment process starting
      from folded DNA to achieve high-density, uniform DNA alignment on an Au(111)
      surface. We demonstrate that folded DNA plays a critical role in avoiding DNA
      aggregation and distributing the DNA uniformly on an Au(111) surface at the
      greatest density and quality ever attained. We also verify that the distributed,
      folded DNA can be stimulated to align only when the appropriate buffer flow is
      applied. This selective self-sensing DNA alignment on an Au surface will be a key
      technology for creating dynamic DNA sensors and switches.

PMID- 18348522
TI  - Perturbations to the geometric and electronic structure of the CuA site: factors
      that influence delocalization and their contributions to electron transfer.
AB  - Using a combination of electronic spectroscopies and DFT calculations, the effect
      of pH perturbation on the geometric and electronic structure of the CuA site has
      been defined. Descriptions are developed for high pH (pH = 7) and low pH (pH = 4)
      forms of CuA azurin and its H120A mutant which address the discrepancies
      concerning the extent of delocalization indicated by multifrequency EPR and ENDOR
      data (J. Am. Chem. Soc. 2005, 127, 7274; Biophys. J. 2002, 82, 2758). Our
      resonance Raman and MCD spectra demonstrate that the low pH and H120A mutant
      forms are essentially identical and are the perturbed forms of the completely
      delocalized high pH CuA site. However, in going from high pH to low pH, a seven
      line hyperfine coupling pattern associated with complete delocalization of the
      electron (S = 1/2) over two Cu coppers (I(Cu) = 3/2) changes into a four-line
      pattern reflecting apparent localization. DFT calculations show that the unpaired
      electron is delocalized in the low pH form and reveal that its four-line
      hyperfine pattern results from the large EPR spectral effects of approximately 1%
      4s orbital contribution of one Cu to the ground-state spin wave function upon
      protonative loss of its His ligand. The contribution of the Cu-Cu interaction to
      electron delocalization in this low symmetry protein site is evaluated, and the
      possible functional significance of the pH-dependent transition in regulating
      proton-coupled electron transfer in cytochrome c oxidase is discussed.

PMID- 18348523
TI  - Synthesis of arylallenes by palladium-catalyzed retro-propargylation of
      homopropargyl alcohols.
AB  - Treatment of tertiary homopropargyl alcohol with aryl halide under palladium
      catalysis provided arylallenes regioselectively. The reaction includes retro
      propargylation, which proceeds in a concerted fashion via a cyclic transition
      state and transfers the stereochemistry of homopropargyl alcohols through C-C
      bond cleavage. The present method enables the use of homopropargyl alcohols as
      allenylmetal equivalents.

PMID- 18348524
TI  - Polydiacetylene liposome arrays for selective potassium detection.
AB  - Potassium is an important cation in biology, and quantitative detection of the
      extracellular potassium level is important. However, selective detection of
      extracellular physiological potassium is a challenging task due to the presence
      of sodium in a much higher concentration. In this contribution, we describe the
      development of practical polydiacetylene (PDA) liposome-based microarrays to
      selectively detect potassium even in the presence of sodium. We utilize the fact
      that the G-rich ssDNA can fold into a G-quadruplex via intramolecular hydrogen
      bonding by wrapping around a potassium ion exclusively. We rationally design the
      PDA liposome in such a way that the G-rich ssDNA probes are presented densely at
      the liposome surface and form bulky quadruplexes upon binding with K+. The
      resulting bulky quadruplexes are sterically hindered and repulse each other and
      impose mechanical stress on the PDA backbone, resulting in the conformational
      change of the ene-yne backbone of the PDA. As a result, polydiacetylene liposomes
      turn into the emissive red phase from the nonfluorescent blue phase.

PMID- 18348525
TI  - Mechanism of intramolecular electron transfer in the photoexcited Zn-substituted
      cytochrome c: theoretical and experimental perspective.
AB  - Photoinduced electron transfer (ET) in zinc-substituted cytochrome c (Zn-cyt c)
      has been utilized in many studies on the long-range ET in protein. Attempting to
      understand its ET mechanism in terms of electronic structure of the molecule, we
      have calculated an all-electron wave function for the ground-state of Zn-cyt c on
      the basis of density functional theory (DFT). The four molecular orbitals (MOs)
      responsible for excitation by UV-vis light (Gouterman's 4-orbitals) are assigned
      on the basis of the excited states of chromophore model for Zn-porphine complex
      calculated with the time-dependent DFT method. ET rates between each Gouterman's
      4-orbitals and other MOs were estimated using Fermi's golden rule. It appeared
      that the two occupied MOs of the 4-orbitals show exclusively higher ET rate
      from/to particular MOs that localize on outermost amino acid residues (Lys 7 or
      Asn 54), respectively, whereas ET rates involving the two unoccupied MOs of the 4
      orbitals are much slower. These results imply that the intramolecular ET in
      photoexcited Zn-cyt c is governed by the hole transfer through occupied MOs. The
      couplings of MOs between zinc porphyrin core and specific amino acid residues on
      the protein surface have been demonstrated in Zn-cyt c immobilized on an Au
      electrode via carboxylic acid group-terminated self-assembled monolayer. The Zn
      cyt c-modified electrode showed photocurrents responsible for photoillumination.
      The action spectrum of the photocurrent was identical with the absorption
      spectrum of Zn-cyt c, indicating photoinduced electron conduction via occupied
      MOs. The voltage dependence of the photocurrent appeared to be linear and
      bidirectional like a photoconductor, which strongly supports the intramolecular
      ET mechanism in Zn-cyt c proposed on the basis of the theoretical calculations.

PMID- 18348526
TI  - Synthesis of ordered mesoporous NiO with crystalline walls and a bimodal pore
      size distribution.
AB  - A mesoporous solid with crystalline walls and an ordered pore structure
      exhibiting a bimodal pore size distribution (3.3 and 11 nm diameter pores) has
      been synthesized. Previous attempts to synthesize solids with large ordered
      mesopores by hard templating focused on the preparation of templates with thick
      walls (the thick walls become the pores in the target materials), something that
      has proved difficult to achieve. Here the large pores (11 nm) do not depend on
      the synthesis of a template with thick walls but instead on controlling the
      microporous bridging between the two sets of mesopores in the KIT-6 template.
      Such control determines the relative proportion of the two pore sizes. The wall
      thickness of the 3D cubic NiO mesopore has also been varied. Preliminary magnetic
      characterization indicates the freezing of uncompensated moments or blocking of
      superparamagnetism.

PMID- 18348527
TI  - Composition of phenolic compounds and antioxidant activity of commercial aqueous
      smoke flavorings.
AB  - The antioxidant activity of 12 aqueous commercial smoke flavorings used in the
      food industry was determined by two methods: bleaching of the carotenoid crocin
      and scavenging of the DPPH radical. The reaction with the DPPH radical was
      evaluated by calculating the effective concentration (EC50) and the antiradical
      efficiency (AE). A gas chromatography-mass spectrometry method was, moreover,
      used for the determination of 2-methoxyphenols, 2,6-dimethoxyphenols, and
      dihydroxybenzenes. The methoxyphenols were extracted from the aqueous smoke by
      dichloromethane, and also the residue aqueous phase was analyzed to determine the
      more water-soluble dihydroxybenzenes. The recovery and the repeatability of the
      method are reported. The total phenolic concentrations of the smoke flavorings
      showed a wide range, from about 1000 to 25000 mg/kg. Considering the three
      classes of compounds, the concentrations were about 300-3000 mg/kg for the 2
      methoxyphenols, 200-11000 mg/kg for the 2,6-dimethoxyphenols, and 140-10000 mg/kg
      for the dihydroxybenzenes. The range of the antioxidant activities of the smoke
      flavorings was wide, reflecting the wide range of the phenolic concentrations.
      Good correlations were obtained between the total phenolic concentration and the
      antioxidant activities determined by both the DPPH and crocin assays.

PMID- 18348528
TI  - Synthesis and biological evaluation of novel C(6) modified baicalein derivatives
      as antioxidative agents.
AB  - Baicalein, one of the major flavones, was found to be responsible for the
      antioxidative activity of the traditional Chinese medicinal herb Huang-Qin (
      Scutellaria baicalensis Georgi), which is widely used as an antioxidative, anti
      inflammatory, and antitumor agent. The hydroxyl group of the A ring of the
      baicalein was alkylated at position 6 with terpenoids such as prenyl, geranyl,
      and farnesyl groups, and their free radical scavenging activities and glutathione
      (GSH) depletion capacities were examined. Their free radical scavenging activity
      was measured according to the 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic
      acid) (ABTS(*+)) scavenging method. Baicalein and newly synthesized baicalein
      derivatives were found to be good free radical scavengers. Flow cytometrical
      method was employed to measure the intracellular antioxidative activity and GSH
      depletion capacity of these derivatives in human acute monocytic leukemia cell
      line (THP-1). It was also found that baicalein and its derivatives could decrease
      the levels of exogenous cumene hydroperoxide and H2O2 in THP-1 cells. These
      compounds also could significantly inhibit the intracellular GSH depletion
      induced by cumene hydroperoxide in THP-1 cells. The production of cumene
      hydroperoxide-induced Bax, a pro-apoptotic related protein, could also be
      inhibited by baicalein and its derivatives. These results suggested that
      baicalein and its derivatives could be beneficial to human health.

PMID- 18348529
TI  - Isolation and structure elucidation of antioxidant polyphenols from quince
      (Cydonia vulgaris) peels.
AB  - Thirteen new compounds, as well as 16 already known, have been isolated from
      organic extracts of peels of Cydonia vulgaris, a fruit of a shrub belonging to
      the same tribe as the apple. All of the structures were elucidated by EI- or ESI
      MS and (1)H and (13)C NMR after purification of individual compounds by HPLC.
      Thirteen fatty acid esters of cinnamyl alcohols, three fatty acid esters of
      hydroxybenzoic acid, three fatty acid esters of hydroxybenzaldehyde, three
      glucosides of aromatic acids, four chlorogenic acids, two flavonols, and a
      benzylamine have been identified. The fatty acid moieties have been identified by
      GC-MS analysis of the methanolysis products. All of the compounds were tested for
      their radical scavenging and antioxidant activities by measuring their capacity
      to scavenge the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical and anion
      superoxide radical and to induce the reduction of Mo(VI) to Mo(V). The
      chlorogenic acids and the flavonols exhibited more antioxidant and radical
      scavenger capacity than the positive standards alpha-tocopherol and ascorbic
      acid. The results of the tests were analyzed by cluster analysis that grouped all
      of the compounds on the basis of the substituents on the aromatic ring.

PMID- 18348531
TI  - Polymer masked-unmasked protein therapy. 1. Bioresponsive dextrin-trypsin and 
      melanocyte stimulating hormone conjugates designed for alpha-amylase activation.
AB  - Polymer-protein conjugation, particularly PEGylation, is well-established as a
      means of increasing circulation time, reducing antigenicity, and improving the
      stability of protein therapeutics. However, PEG has limitations including lack of
      polymer biodegradability, and conjugation can diminish or modify protein
      activity. The aim of this study was to explore a novel approach for polymer
      protein modification called polymer-masking-unmasking-protein therapy (PUMPT),
      the hypothesis being that conjugation of a biodegradable polymer to a protein
      would protect it and mask activity in transit, while enabling controlled
      reinstatement of activity at the target site by triggered degradation of the
      polymeric component. To test this hypothesis, dextrin (alpha-1,4 polyglucose, a
      natural polymer degraded by alpha-amylase) was conjugated to trypsin as a model
      enzyme or to melanocyte stimulating hormone (MSH) as a model receptor-binding
      ligand. The effect of dextrin molecular weight (7700, and 47200 g/mol) and degree
      of succinoylation (9-32 mol %) on its ability to mask/unmask trypsin activity was
      assessed using N-benzoyl-L-arginine-p-nitroanilide (L-BAPNA). Dextrin conjugation
      reduced enzyme activity by 34-69% depending on the molecular weight and degree of
      succinoylation of dextrin. However, incubation with alpha-amylase led to
      reinstatement of activity to a maximum of 92-115%. The highest molecular dextrin
      (26 mol % succinoylation) gave optimum trypsin masking-unmasking. This
      intermediate was used to synthesize a dextrin-MSH conjugate (dextrin Mw = 47200
      g/mol; MSH content 37 wt %), and its biological activity (+/-alpha-amylase) was
      assessed by measuring melanin production by murine melanoma (B16F10) cells.
      Conjugation reduced melanin production to 11%, but addition of alpha-amylase was
      able to restore activity to 33% of the control value. These were the first
      studies to confirm the potential of PUMPT for further application to clinically
      important protein therapeutics. The choice of masking polymer, activation
      mechanism, and the rate of unmasking can be tailored to therapeutic application.

PMID- 18348532
TI  - Physicochemical characterization of thermoresponsive poly(N-isopropylacrylamide)
      poly(ethylene imine) graft copolymers.
AB  - Synthetic polycations have shown promise as gene delivery vehicles but suffer
      from an unacceptable toxicity and low transfection efficiency. Novel
      architectures are being explored to increase transfection efficiency, including
      copolymers with a thermoresponsive character. The physicochemical
      characterization of a family of copolymers comprising a core of the cationic
      polymer poly(ethylene imine) (PEI) with differing thermoresponsive poly( N
      isopropylacrylamide) (PNIPAM) grafts has been carried out using pulsed-gradient
      spin-echo NMR (PGSE-NMR) and small-angle neutron scattering (SANS). For the
      copolymers that have longer chain PNIPAM grafts, there is clear evidence of the
      collapse of the grafts with increasing temperature and the associated emergence
      of an attractive interpolymer interaction. These facets depend on the number of
      PNIPAM grafts attached to the PEI core. While a collapse in the smaller PNIPAM
      grafts is observed for the third polymer, there is no appearance of the
      interpolymer attractive interaction. These observations provide further insight
      into the association behavior of these copolymers, which is fundamental to
      developing a full understanding of how they interact with nucleic acids.
      Furthermore, the differing behaviors of the three copolymers over temperatures in
      which the PNIPAM blocks undergo coil-to-globule transitions is indicative of
      changes in the presentation of charged-core and hydrophobic chain components,
      which are key factors affecting nucleic acid binding and, ultimately, cell
      transfection ability.

PMID- 18348533
TI  - Glycosidic constituents of the tubers of Gymnadenia conopsea.
AB  - Ten minor new glycosidic constituents (1- 10), together with 10 known compounds,
      have been isolated from a neuroprotective fraction of an ethanolic extract of the
      tubers of Gymnadenia conopsea. The structures of 1-10 were determined using
      spectroscopic and chemical methods. The compounds isolated were evaluated for
      activity in in vitro assays for acetylcholine esterase and monoamine oxidase
      inhibitory activities.

PMID- 18348534
TI  - Steroids and flavonoids from Physalis alkekengi var. franchetii and their
      inhibitory effects on nitric oxide production.
AB  - Four new steroidal compounds possessing a rare 13,14-seco-16,24-cycloergostane
      skeleton, physalin Y ( 1), physalin Z ( 2), physalin I ( 6), and physalin II (
      7), were isolated from the 80% EtOH extract of calyces from Physalis alkekengi
      var. franchetii together with 11 known steroids ( 3- 5 and 8- 15) and eight
      flavonoids ( 16- 23). The structures of the new compounds were elucidated
      primarily on the basis of 1D and 2D NMR and mass spectroscopic studies. The
      relative configuration of the 3-OH group of 3, 4, and 5 was also established or
      re-established. The inhibitory effects of compounds 1- 23 on nitric oxide
      production in lipopolysaccaride-activated macrophages were evaluated.

PMID- 18348535
TI  - Abietane diterpenoids from Clerodendrum bungei.
AB  - Five new naturally occurring abietane diterpenoids (1-5) along with three known
      diterpenoids (6-8) were isolated from an acetone-soluble extract of the roots of
      Clerodendrum bungei. The structures of the new compounds were elucidated on the
      basis of spectroscopic analysis and chemical methods. In addition, all compounds
      were evaluated for cytotoxic activity against the cultured B16 (murine melanoma),
      HGC-27 (human gastric), and HEK-293 (human epithelial kidney) cell lines.
      Uncinatone (7) exhibited moderate cytotoxicity, inhibited cell proliferation, and
      induced cell-cycle G(2)/M phase arrest.

PMID- 18348536
TI  - An electron spin-polarized signal of the P800+A1(Q)- state in the homodimeric
      reaction center core complex of Heliobacterium modesticaldum.
AB  - The function of menaquinone as electron acceptor A 1 was identified by EPR in the
      purified type 1 homodimeric reaction center core complex (RC core) of an
      anoxygenic photosynthetic bacterium, Heliobacterium modesticaldum. After
      illumination of the RC core at 210 K in the absence and presence of dithionite,
      we detected the radical of a special pair of bacteriochlorophyll g molecules
      (P800 (+)) at g = 2.0033 and a quinone-type radical at g = 2.0062, respectively,
      at 14 K. Flash excitation of the dark-frozen RC core at 14 K induced two types of
      transient EPR signals, i.e., the P800 (+) radical that decayed with a time
      constant of 3.7 ms and a much faster decay component that showed the electron
      spin polarization (ESP) pattern of E/A (E, emission; A, absorption). The latter
      one was assigned to the P800 (+)F X (-) radical pair state. A new ESP signal that
      had an apparent A/E/A/E pattern extended to the lower-magnetic-field side was
      transiently induced by the flash excitation in the RC core that was
      preilluminated at 210 K in the presence of ascorbate and subsequently cooled to
      14 K in the light. The 210 K preillumination of the RC core in the presence of
      dithionite led to accumulation of the dark stable semiquinone-type signal at g =
      2.0062 and increased the intensity of the light-induced P800 triplet signal.
      Flash excitation at 14 K induced the smaller A/E/A/E-type signal that had the
      greater contribution of the lower-magnetic-field envelope. This ESP signal could
      thus be ascribed to the P800 (+)A 1 (-) radical pair. The kinetics and spectral
      shape of this ESP signal suggest that menaquinone serves as secondary electron
      acceptor A 1 with the molecular orientation of its ring being somewhat different
      from that of phylloquinone in photosystem I.

PMID- 18348537
TI  - A renewed model of CNA regulation involving its C-terminal regulatory domain and
      CaM.
AB  - Calcineurin is composed of a catalytic subunit (CNA) and a regulatory subunit
      (CNB). CNA contains the catalytic domain and three regulatory domains: a CNB
      binding domain (BBH), a C-terminal calmodulin-binding domain (CBD), and an
      autoinhibitory domain (AID). We constructed a series of mutants of CNA to explore
      the regulatory role of its C-terminal regulatory domain and CaM. We demonstrated
      a more precise mechanism of CNA regulation by C-terminal residues 389-511 in the
      presence of CNB. First, we showed that residues 389-413, which were identified in
      previous work as constituting a CaM binding domain (CBD), also have an
      autoinhibiting function. We also found that residues 389-413 were not sufficient
      for CaM binding and that the CBD comprises at least residues 389-456. In
      conclusion, two distinct segments of the C-terminal regulatory region (389-511)
      of CNA inhibit enzyme activity: residues 389-413 interact with the CNB binding
      helix (BBH), and residues 457-482 with the active center of CNA.

PMID- 18348538
TI  - Conformational polymorphism in organic crystals.
AB  - Polymorphs are different crystalline modifications of the same chemical
      substance. When different conformers of the same molecule occur in different
      crystal forms, the phenomenon is termed conformational polymorphism.
      Occasionally, more than one conformer is present in the same crystal structure.
      The influence of molecular conformation changes on the formation and stability of
      polymorphs is the focus of this Account. X-ray crystal structures of
      conformational polymorphs were analyzed to understand the interplay of
      intramolecular (conformer) and intermolecular (lattice) energy in the
      crystallization and stability of polymorphs. Polymorphic structures stabilized by
      strong O-H...O/N-H...O hydrogen bonds, weak C-H...O interactions, and close
      packing were considered. 4,4-Diphenyl-2,5-cyclohexadienone (1) and bis(p-tolyl)
      ketone p-tosylhydrazone (3) are prototypes of C-H...O and N-H...O hydrogen-bonded
      structures. Distance-angle scatter plots of O-H...O and C-H...O hydrogen bonds
      extracted from the Cambridge Structural Database indicate that polymorphs with a
      larger number of symmetry-independent molecules (high Z') generally have better
      interactions when compared with the polymorphs with lower Z' values, with the
      implication that these symmetry-independent molecules have different
      conformations. Since molecular conformer (E(conf)) and crystal lattice (U(latt))
      energy differences are of the same magnitude in organic crystals (typically <5
      kcal mol(-1)), situations wherein these two factors compensate or cancel one
      another are illustrative. Calculation of conformer and lattice energies using
      Gaussian 03 and Cerius(2) in 23 recently published polymorph sets shows that a
      strained conformer (higher E(conf)) is stabilized by stronger interactions or
      better crystal packing (lower U(latt)) in two-thirds of the cases, whereas there
      is no energy balance in the remaining structures. Organic molecules with flexible
      torsions and low-energy conformers have a greater likelihood of exhibiting
      polymorphism because (1) different conformations lead to new hydrogen-bonding and
      close-packing modes and (2) the tradeoff reduces the total energy difference
      between alternative crystal structures. As a test case, polymorph promiscuity in
      fuchsones (6) is related to the conformational diversity at the exo-methylene
      phenyl rings and the small energy difference computed for dimethyl fuchsone
      polymorphs. These ideas find application in the design of putative pharmaceutical
      polymorphs and crystal structure prediction.

PMID- 18348539
TI  - Fluorogenic polydiacetylene supramolecules: immobilization, micropatterning, and
      application to label-free chemosensors.
AB  - This Account describes a new strategy for the preparation of label-free sensor
      systems based on the fluorogenic properties of the conjugated polymer,
      polydiacetylene (PDA). PDA has been extensively investigated as a sensor matrix,
      owing to a brilliant blue-to-red color transition that takes place in response to
      environmental perturbations. It has been known for some time that "blue-phase"
      PDAs are nonfluorescent while their "red-phase" counterparts fluoresce. For the
      most part, however, the significance of the different fluorogenic properties of
      PDAs has been ignored in the context of sensor applications. In the course of
      developing PDA-based sensors, we discovered that PDA vesicles can be readily
      immobilized on solid substrates. This is an attractive property of PDAs since it
      leads to the combined advantages of the vesicle sensors (which have three
      dimensional interactions between sensor and target molecules) and film sensors
      (which are applicable to a two-dimensional array or chip format). Stable blue
      phase immobilized PDAs can be prepared by employing one of three strategies
      involving the formation of covalent adducts, biotin-avidin complexes, or
      complexes formed through nonspecific physical adsorption. A procedure for
      generating well-patterned fluorescence images is necessary for the immobilized
      PDAs to function in chip-based sensor systems. Patterned fluorescence images are
      readily constructed by employing (1) the photolithographic technique, (2) the
      micromolding in capillaries (MIMIC) method, or (3) an array spotting system. Heat
      treatment of the patterned "blue-phase" PDA vesicles transforms the
      nonfluorescent images into their fluorescent red forms. The observation that
      finely resolved fluorescence patterns can be generated by heat treatment of
      microarrayed PDAs is highly significant in that it indicates that fluorescence
      signals might be produced by specific molecular recognition events. Indeed, red
      fluorescence emission is observed when immobilized PDAs are subjected to specific
      molecular recognition events, such as ligand--cyclodextrin or protein-protein
      interactions. The facile immobilization of PDA vesicles on solid substrates and
      the affinity-induced fluorescence emission combine to make this system applicable
      to the fabrication of label-free PDA sensors. Since in theory any molecular
      recognition event that promotes the blue-to-red color transition of PDAs should
      result in the generation of fluorescence, it should be possible to reformat a
      variety of previously described colorimetric PDA sensors into fluorescence-based
      sensor systems. The fluorescence properties of PDAs, when combined with modern
      methods for the fabrication of microarrays, should stimulate the development of a
      number of new label-free chemosensor systems.

PMID- 18348540
TI  - A ZnO nanorod inorganic/organic heterostructure light-emitting diode emitting at
      342 nm.
AB  - An inorganic/organic heterostructure light-emitting diode consisting of the hole
      transporting layer N, N'-di(naphth-2-yl)- N, N'-diphenylbenzidine (NPB) and n
      type ZnO nanorods fabricated by hydrothermal decomposition is reported.
      Poly(methyl methacrylate) was used to form a smooth surface on top of ZnO nanorod
      array with ZnO nanorod tops exposed for subsequent NPB deposition. An unusual
      ultraviolet emission at 342 nm was observed in the electroluminescence spectrum.
      Compared to band gap energy of ZnO (3.37 eV), the excitonic emission is blue
      shifted and broadened. The mechanism of the blue shift is discussed in terms of
      the energy band diagram of the heterostructure.

PMID- 18348541
TI  - Ultra performance liquid chromatography isotope dilution tandem mass spectrometry
      for the absolute quantification of proteins and peptides.
AB  - A selective, rapid, and sensitive 12.7-min ultra performance liquid
      chromatography-isotope dilution tandem mass spectrometry (UPLC-ID/MS/MS) method
      was developed and compared to conventional high-performance liquid chromatography
      isotope dilution tandem mass spectrometry (HPLC-ID/MS/MS) for the absolute
      quantitative determination of multiple proteins from complex matrixes. The UPLC
      analysis was carried out on an Acquity UPLC ethylene-bridged hybrid (BEH) C18
      reversed-phase column (50 x 2.1 mm i.d., 1.7-microm particle size) with gradient
      elution at a flow rate of 300 microL/min. For the HPLC separation, a similar
      gradient profile on a reversed-phase C18 column with dimensions of 150 x 1.0 mm
      at a flow rate of 30 microL/min was utilized. The aqueous and organic mobile
      phases were 0.1% formic acid in water and acetonitrile, respectively. Detection
      was performed on a triple-quadrupole mass spectrometer operated in the multiple
      reaction monitoring mode. Linear calibration curves were obtained in the
      concentration range of 10-90 fmol/microL. Relative standard deviation values
      equal to or less than 6.5% were obtained by the UPLC-ID/MS/MS method, thus
      demonstrating performance equivalent to conventional HPLC-ID/MS/MS for isotope
      dilution quantification of peptides and proteins. UPLC provides additional
      dimensions of rapid analysis time and high-sample throughput, which expands
      laboratory emergency response capabilities over conventional HPLC.

PMID- 18348542
TI  - Full on-chip nanoliter immunoassay by geometrical magnetic trapping of
      nanoparticle chains.
AB  - We propose an original concept to perform a complete on-chip sandwich immunoassay
      on magnetic nanoparticles that are self-assembled in chains in a uniform magnetic
      field. The magnetic chains are retained over periodically enlarged cross sections
      of a microfluidic channel. Thereby they strongly interact with the flow and
      rapidly capture the total of a low number of target molecules from nanoliter
      sample volumes. As an example, we demonstrate the detection of murine monoclonal
      antibodies in a noncompetitive sandwich immunoassay with a detection limit of 1
      ng mL(-1) in nanoliters of hybridoma cell culture medium.

PMID- 18348543
TI  - Chemically selective displacers for high-resolution protein separations in ion
      exchange systems: effect of displacer-protein interactions.
AB  - Displacer lead compounds were selected from a commercially available database to
      identify potential selective displacers for a binary protein mixture in ion
      exchange chromatography. Parallel batch screening experiments were carried out
      with these lead compounds to study the effect of displacer concentration on the
      relative amounts of the proteins displaced. Experiments were conducted with a
      mixture containing ribonuclease A and alpha-chymo-trypsinogen A which exhibited
      very similar retention behavior under linear gradient conditions. The batch
      displacement results indicated that most of these lead compounds were indeed
      selective for displacing ribonuclease A. In fact, one of these displacers
      exhibited extremely high selectivity, displacing essentially all of the
      ribonuclease A while displacing minimal alpha-chymotrypsinogen A at a displacer
      concentration of 10 mM. These results were validated under column conditions,
      with the ribonuclease A being displaced and the alpha-chymotrypsinogen A
      remaining on the column after the displacer breakthrough. In order to examine
      whether this was mass action or chemically selective displacement, an affinity
      ranking plot based on the Steric Mass Action (SMA) model was generated, and the
      results confirmed that this was not a mass action displacement. In order to test
      the hypothesis that displacer protein binding was playing a role in these
      separations, Surface Plasmon Resonance (SPR) was carried out. The results suggest
      that while the chemically selective displacer interacted with alpha-chymo
      trypsinogen A, it had no interaction with ribonuclease A. The ability to exploit
      protein displacer binding in concert with appropriate displacer resin affinities
      opens up new possibilities for creating selective displacement systems.

PMID- 18348544
TI  - ReaxFF reactive force field for solid oxide fuel cell systems with application to
      oxygen ion transport in yttria-stabilized zirconia.
AB  - We present the ReaxFF reactive force field developed to provide a first
      principles-based description of oxygen ion transport through yttria-stabilized
      zirconia (YSZ) solid oxide fuel cell (SOFC) membranes. All parameters for ReaxFF
      were optimized to reproduce quantum mechanical (QM) calculations on relevant
      condensed phase and cluster systems. We validated the use of ReaxFF for fuel cell
      applications by using it in molecular dynamics (MD) simulations to predict the
      oxygen ion diffusion coefficient in yttria-stabilized zirconia as a function of
      temperature. These values are in excellent agreement with experimental results,
      setting the stage for the use of ReaxFF to model the transport of oxygen ions
      through the YSZ electrolyte for SOFC. Because ReaxFF descriptions are already
      available for some catalysts (e.g., Ni and Pt) and under development for other
      high-temperature catalysts, we can now consider fully first-principles-based
      simulations of the critical functions in SOFC, enabling the possibility of in
      silico optimization of these materials. That is, we can now consider using theory
      and simulation to examine the effect of materials modifications on both the
      catalysts and transport processes in SOFC.

PMID- 18348545
TI  - Density functional theory calculations of the lowest energy quintet and triplet
      states of model hemes: role of functional, basis set, and zero-point energy
      corrections.
AB  - We investigated the effect of several computational variables, including the
      choice of the basis set, application of symmetry constraints, and zero-point
      energy (ZPE) corrections, on the structural parameters and predicted ground
      electronic state of model 5-coordinate hemes (iron(II) porphines axially
      coordinated by a single imidazole or 2-methylimidazole). We studied the
      performance of B3LYP and B3PW91 with eight Pople-style basis sets (up to 6
      311+G*) and B97-1, OLYP, and TPSS functionals with 6-31G and 6-31G* basis sets.
      Only hybrid functionals B3LYP, B3PW91, and B97-1 reproduced the quintet ground
      state of the model hemes. With a given functional, the choice of the basis set
      caused up to 2.7 kcal/mol variation of the quintet-triplet electronic energy gap
      (DeltaEel), in several cases, resulting in the inversion of the sign of DeltaEel.
      Single-point energy calculations with triple-zeta basis sets of the Pople (up to
      6-311G++(2d,2p)), Ahlrichs (TZVP and TZVPP), and Dunning (cc-pVTZ) families
      showed the same trend. The zero-point energy of the quintet state was
      approximately 1 kcal/mol lower than that of the triplet, and accounting for ZPE
      corrections was crucial for establishing the ground state if the electronic
      energy of the triplet state was approximately 1 kcal/mol less than that of the
      quintet. Within a given model chemistry, effects of symmetry constraints and of a
      "tense" structure of the iron porphine fragment coordinated to 2-methylimidazole
      on DeltaEel were limited to 0.3 kcal/mol. For both model hemes the best agreement
      with crystallographic structural data was achieved with small 6-31G and 6-31G*
      basis sets. Deviation of the computed frequency of the Fe-Im stretching mode from
      the experimental value with the basis set decreased in the order: nonaugmented
      basis sets, basis sets with polarization functions, and basis sets with
      polarization and diffuse functions. Contraction of Pople-style basis sets (double
      zeta or triple-zeta) affected the results insignificantly for iron(II) porphyrin
      coordinated with imidazole. Poor performance of a "locally dense" basis set with
      a large number of basis functions on the Fe center was observed in calculation of
      quintet-triplet gaps. Our results lead to a series of suggestions for density
      functional theory calculations of quintet-triplet energy gaps in ferrohemes with
      a single axial imidazole; these suggestions are potentially applicable for other
      transition-metal complexes.

PMID- 18348546
TI  - First reported correlation between the calculated gas-phase proton
      macroaffinities of some metal complexes with their measured formation constants
      in solution: Zn(II) complexes of a series of tripodal aliphatic tetraamines.
AB  - A theoretical study on the first protonation step of a series of metal complexes
      with the general formula {M(N[(CH2)nNH2][(CH2)mNH2][(CH2)pNH2])2+} (n = m = p =
      2, tren; n = 3, m = p = 2, pee; n = m = 3, p = 2, ppe; n = m = p = 3, tpt; n = 2,
      m = 3, p = 4, epb; and n = m = 3, p = 4, ppb; and M = Zn2+) was reported using
      both the Hartree-Fock and DFT (B3LYP) levels of theory. For the first time, two
      kinds of our recently published definitions for gas-phase proton affinities of
      polybasic ligands, proton microaffinity and proton macroaffinity, were extended
      to their metal complexes. There is a good correlation between the calculated gas
      phase proton macroaffinities and the corresponding formation constants in
      solution.

PMID- 18348547
TI  - Prediction of vibrational frequencies of UO2(2+) at the CCSD(T) level.
AB  - Electronic structure calculations at the coupled cluster (CCSD(T)) and density
      functional theory levels with relativistic effective core potentials and large
      basis sets were used to predict the isolated uranyl ion frequencies. The effects
      of anharmonicity and spin-orbit corrections on the harmonic frequencies were
      calculated. The anharmonic effects are larger than the spin-orbit corrections,
      but both are small. The anharmonic effects decreased all the frequencies, whereas
      the spin-orbit corrections increased the stretches and decreased the bend.
      Overall, these two corrections decreased the harmonic asymmetric stretch
      frequency by 6 cm-1, the symmetric stretch by 3 cm-1, and the bend by 3 cm-1. The
      best calculated values for UO22+ for the asymmetric stretch, symmetric stretch,
      and bend were 1113, 1032, and 174 cm-1, respectively. The separation between the
      asymmetric and the symmetric stretch band origins was predicted to be 81 cm-1,
      which is consistent with experimental trends for substituted uranyls in solution
      and in the solid state. The anharmonic vibrational frequencies of the
      isoelectronic ThO2 molecule also were calculated and compared to experiment to
      calibrate the UO22+ results.

PMID- 18348548
TI  - Understanding the electronic structure, reactivity, and hydrogen bonding for a
      1,2-diphosphonium dication.
AB  - The experimental charge density for hexamethyldiphosphonium ditriflate has been
      determined from low-temperature high-resolution X-ray diffraction data. These
      results have been compared with theoretically calculated values for the isolated
      gas-phase compound. Analysis of the topological and atomic basin properties has
      provided insight into the exact nature of the P-P bond in both the crystalline
      and the gas-phase structures. The rho(b)(r) and nabla2rho(b)(r) values highlight
      the covalent nature of the P-P bond, while the atomic charges indicate a
      localization of the positive charges on the two phosphorus atoms. This seems to
      indicate that a covalent bond is formed despite a strong electrostatic repulsion
      between these two heteroatoms. The topological properties and electrostatic
      potentials have also been shown to provide significant insight into the chemical
      reactivity of the title compound. A topological analysis of P2Me4, P2Me5(+), and
      P2Me6(+2) species has provided information about the progression of the P-P bond
      in the synthesis of the title compound. An investigation of the different
      hydrogen-bonding networks present in the crystalline and gas-phase structures,
      along with their affect on the electronic structure of the title compound has
      also been investigated. This has all led to significant new insight into the
      electronic structure, reactivity, and weak hydrogen bonding in prototypical 1,2
      diphosphonium dications.